PMID- 29319595
TI  - Pythium Keratitis Leading to Fatal Cavernous Sinus Thrombophlebitis.
AB  - PURPOSE: To report a case of Pythium insidiosum keratitis leading to fatal
      cavernous sinus thrombophlebitis. METHODS: Case report. RESULTS: A 70-year-old
      man presented with excruciating pain, redness, and diminution of vision in his
      left eye for 2 weeks after washing his hair with tap water. A total corneal ulcer
      with surrounding infiltrates and associated corneal thinning was present. Corneal
      scraping revealed the presence of Gram-positive cocci. KOH wet mount and in vivo
      confocal microscopy revealed branching hyphae. Combined antibacterial and
      antifungal treatment was started, but 4 days later, the ulcer showed signs of
      worsening with perforation for which a large therapeutic penetrating keratoplasty
      was done. The host cornea showed branching septate hyphae on Sabarouds Dextrose
      Agar. Two weeks later, the patient developed left eye proptosis with associated
      extraocular movement restriction. Magnetic resonance imaging of the head and
      orbit revealed cavernous sinus thrombophlebitis. Lid sparing partial exenteration
      was performed. Polymerase chain reaction revealed P. insidiosum. The patient
      subsequently developed a cerebrovascular attack and died of its complications.
      CONCLUSIONS: Ocular pythiosis may lead to cavernous sinus thrombophlebitis and
      can even be life threatening. Timely diagnosis and early radical surgery are of
      value. A high index of suspicion must be kept for P. insidiosum in cases with
      suspected fungal etiology not responding to conventional treatment.

PMID- 29319596
TI  - Obstructive Sleep Apnea Assessed by Overnight Polysomnography in Patients With
      Keratoconus.
AB  - PURPOSE: To determine the prevalence of obstructive sleep apnea (OSA) in patients
      with keratoconus (KCN) and to evaluate the association between the severity of
      KCN and OSA. METHODS: OSA was diagnosed with an overnight home sleep apnea test.
      As estimated by home monitoring, an apnea-hypopnea index threshold of >=5 sleep
      related obstructive breathing events per hour was considered suggestive of OSA.
      For grading KCN severity (Amsler-Krumeich classification), slit-lamp
      biomicroscopy, corneal topography, and pachymetry measurements were performed.
      Preoperative measurements were included in the analysis for patients who had
      undergone surgery for KCN. RESULTS: The study sample consisted of 50
      consecutively enrolled patients: 33 men; mean age +/- SD 43.6 +/- 11.8 years;
      body mass index 29.7 +/- 7.3 kg/m; and neck circumference 40.0 +/- 3.4 cm. The
      overall prevalence of OSA was 38% (6 women and 13 men). Patients with OSA were
      older (49.8 +/- 9.3 vs. 37.5 +/- 10.8 years; P < 0.01) and had a higher body mass
      index (34.7 +/- 8.1 vs. 26.2 +/- 4.8 kg/m; P <0.01), neck circumference (41.2 +/-
      2.6 vs. 38.7 +/- 3.6 cm; P < 0.01), and cylinder diopter (5.98 +/- 1.94 vs. 4.05
      +/- 3.55 D; P = 0.045) compared with those without OSA. No significant
      association was found between OSA severity and ocular parameters and KCN grade.
      CONCLUSIONS: As measured by overnight home sleep apnea testing, OSA was 10 to 20
      times more prevalent among patients with KCN than the rate reported for the
      general population. The rate lies between the prevalence estimated from sleep
      study data of self-reported diagnosis of OSA and the risk of developing OSA as
      determined by the Berlin Questionnaire.

PMID- 29319597
TI  - Repeated Same-Day Versus Single Tomography Measurements of Keratoconic Eyes for
      Analysis of Disease Progression.
AB  - PURPOSE: Corneal tomography is used to assess progression of keratoconus and to
      direct clinical decisions regarding corneal cross-linking. The purpose of this
      study was to analyze the variability of repeated Scheimpflug-tomography (Pentacam
      Classic; Oculus, Wetzlar, Germany) measurements of keratoconic eyes in a clinical
      setting and to assess the validity of such measurements as a clinical decision
      making tool. METHODS: Eighty keratoconic eyes of 45 patients (age range 16-32
      years) were examined at baseline and after follow-up periods of 3 to 6 months
      using 3 consecutive tomography measurements at each visit. Minimum corneal
      thickness and anterior sagittal curvature map parameters were studied [simulated
      keratometry (K) astigmatism (SimKast); maximum simulated K-reading (SimKmax);
      average SimK (SimKave); maximum K-readings on the 3-mm (Kmax3) and 5-mm (Kmax5)
      rings; and maximum K-reading (Kmax)]. RESULTS: When comparing the first
      measurements at the first and second visits, respectively, 9% to 20% of eyes were
      classified as progressive depending on which parameter was chosen. Using the
      average of 3 consecutive measurements at each visit, 5% to 19% of eyes were
      classified as progressive. An increase in the SD of 3 consecutive measurements of
      SimKast (SD_SimKast) at the first visit of 1 diopter makes true progression of
      keratoconus 3.6 times more likely (odds ratio = 3.6; 95% confidence interval:
      0.846-16.027; area under the curve = 0.70). CONCLUSIONS: The approach used to
      analyze progression in keratoconus, that is, single versus repeated measurements,
      may confer a great impact on the decision to perform corneal cross-linking
      treatment or not.

PMID- 29319598
TI  - Corneal Collagen Cross-Linking With Riboflavin and Ultraviolet A Light for
      Pediatric Keratoconus: Ten-Year Results.
AB  - PURPOSE: To assess the 10-year follow-up efficacy and safety of riboflavin
      ultraviolet A-induced cross-linking (CXL) in a population of pediatric patients
      aged 18 years and younger with progressive keratoconus (KC). METHODS: The
      prospective longitudinal cohort study included 62 eyes of 47 keratoconic patients
      undergoing epithelium-off CXL who completed 10-year follow-up. The surgical
      procedure was performed in all patients according to the Siena (Dresden modified)
      protocol. Evaluation included uncorrected distance visual acuity, corrected
      distance visual acuity, Scheimpflug corneal tomography, and optical coherence
      tomography demarcation line measurement. Follow-up measurements taken up to 10
      years after treatment were compared with baseline values, and statistical
      analysis was performed using a 2-tailed paired sample Student t test. RESULTS:
      Uncorrected distance visual acuity and corrected distance visual acuity improved
      from 0.45 to 0.23 logarithm of the minimum angle resolution (P = 0.0001) and from
      0.14 to 0.1 logarithm of the minimum angle resolution (P = 0.019). KC stability
      was recorded after 10 years of follow-up in nearly 80% of the patients. The
      overall 10-year follow-up progression rate was 24% including 13 eyes of 9
      patients with Kmax progression over 1 diopter and 2 eyes of 2 patients who
      underwent corneal grafting. CONCLUSIONS: The study demonstrates the ability of
      CXL to slow down KC progression in pediatric patients, improving functional
      performance. Long-term stability may be correlated with CXL-induced delay in
      corneal collagen turnover and with spontaneous age-related KC stabilization. A
      24% regression rate could be contemplated in the patients who were aged 15 years
      and younger at the time of inclusion in the treatment protocol.

PMID- 29319599
TI  - Long-Term Outcome After Penetrating Keratoplasty in a Pedigree With the G177E
      Mutation in the UBIAD1 Gene for Schnyder Corneal Dystrophy.
AB  - PURPOSE: To investigate the long-term surgical outcome after penetrating
      keratoplasty in 5 patients from 1 pedigree with Schnyder corneal dystrophy (SCD),
      resulting from the same UbiA prenyltransferase domain containing 1 (UBIAD1)
      mutation. METHODS: This retrospective study involved 6 eyes of 5 patients who
      underwent penetrating keratoplasty for treatment of SCD. Postoperative surgical
      outcome measures included the analysis of best-corrected visual acuity (BCVA),
      corneal endothelial cell density, and the rates of corneal graft rejection and
      disease recurrence. Genomic DNA was extracted from whole peripheral blood samples
      obtained from each patient at the time of surgery, and mutation analysis of the
      UBIAD1 gene was then performed. RESULTS: All patients were found to have the same
      G177E mutation in the UBIAD1 gene. Mean patient age at the time of surgery was
      61.5 +/- 10.4 years (range, 49-72 yrs), and mean postoperative follow-up period
      was 8.8 +/- 3.1 years (range, 3-11 yrs). Preoperatively, BCVA ranged from
      logarithm of the minimum angle of resolution (logMAR) 1.7 to logMAR 0.22; yet, it
      was found that BCVA had improved to logMAR 0.02 at 3 years postoperatively. Mean
      corneal endothelial cell density at 3, 5, and 8 years postoperatively was 2181,
      1783, and 910 cells/mm, respectively. In all eyes, no disease recurrence or
      corneal graft rejection was observed during the follow-up period, and graft
      transparency was maintained. CONCLUSIONS: Our findings show that the corneal
      grafts in the reported SCD pedigree remained clear with no rejection or disease
      recurrence over the long term.

PMID- 29319600
TI  - Abdominal Muscle Activation During Common Modifications of the Trunk Curl-Up
      Exercise.
AB  - The purpose of this study was to investigate effects of common modifications of
      trunk curl-up exercise on the involvement of the abdominal muscles, particularly
      the deepest muscle layer, transversus abdominis (TrA). Ten healthy females
      performed five different variations of the trunk curl-up at a standardized speed,
      varying the exercise by assuming three different arm positions and applying left
      and right twist. Indwelling fine-wire electromyography (EMG) electrodes were used
      to record from TrA, obliquus internus (OI), obliquus externus (OE) and rectus
      abdominis (RA) unilaterally on the right side. Increasing the load by changing
      the arm position during a straight trunk curl-up increased the EMG of all
      abdominal muscles. OI and TrA showed higher activation during right twist
      compared to left twist whereas OE displayed the opposite pattern. RA did not show
      any change in activation level between twisting directions. The apparent load
      dependency on the activation level of all muscles and the twisting direction
      dependency of all muscles except RA are in keeping with the fiber orientation of
      the muscles. Notably, also TrA, with a less obvious mechanical role with regards
      to fiber orientation, increased activation with load during the straight trunk
      curl-up. However, the highest activation level of TrA during the trunk curl-up
      was only 40 % of a maximum contraction, thus it might not be the most suitable
      strength training exercise for this muscle.

PMID- 29319601
TI  - The MoCA-Memory Index Score: An Efficient Alternative to Paragraph Recall for the
      Detection of Amnestic Mild Cognitive Impairment.
AB  - OBJECTIVE: To compare ability of 2 measures of delayed memory (word list, story
      paragraph) to discriminate Normal Control (NC) subjects from those with amnestic
      mild cognitive impairment (aMCI). METHODS: Demographic, neuropsychological, and
      diagnostic data contributed by 34 Alzheimer's Disease Centers to the National
      Alzheimer's Coordinating Center characterized 2717 individuals with a diagnosis
      of either NC (n=2205) or aMCI (n=512). The Montreal Cognitive Assessment-Memory
      Index Score (MoCA-MIS) assessed delayed word recall, and the Craft Story 21,
      delayed story recall. Logistic regression and receiver operator characteristic
      curves controlling for age, sex, and education assessed the ability of each test
      to differentiate NCs from subjects with aMCI. RESULTS: The MoCA-MIS had
      significantly better sensitivity and specificity (area under the receiver
      operator characteristic curve 0.83 vs. 0.80, P=0.004). At sensitivity 80%, the
      specificity of the MoCA-MIS was 69.1%, compared with 62.8% for the Craft Story.
      CONCLUSIONS: These data suggest that the MoCA-MIS, a recall score from items
      within the MoCA, is better at discriminating NCs from subjects with aMCI than the
      Craft Story. Word recall may be an efficient alternative to paragraph recall for
      diagnostic screening within clinical practice and research settings.

PMID- 29319602
TI  - An Interactional Profile to Assist the Differential Diagnosis of
      Neurodegenerative and Functional Memory Disorders.
AB  - OBJECTIVE: Specialist services for dementia are seeing an increasing number of
      patients. We investigated whether interactional and linguistic features in the
      communication behavior of patients with memory problems could help distinguish
      between those with problems secondary to neurological disorders (ND) and those
      with functional memory disorder (FMD). METHODS: In part 1 of this study, a
      diagnostic scoring aid (DSA) was developed encouraging linguists to provide
      quantitative ratings for 14 interactional features. An optimal cut-off
      differentiating ND and FMD was established by applying the DSA to 30 initial
      patient-doctor memory clinic encounters. In part 2, the DSA was tested
      prospectively in 10 additional cases analyzed independently by 2 conversation
      analysts blinded to medical information. RESULTS: In part 1, the median score of
      the DSA was +5 in ND and -5 in FMD (P<0.001). The optimal numeric DSA cut-off
      (+1) identified patients with ND with a sensitivity of 86.7% and a specificity of
      100%. In part 2, DSA scores of rater 1 correctly predicted 10/10 and those of
      rater 2 predicted 9/10 diagnoses. CONCLUSIONS: This study indicates that
      interactional and linguistic features can help distinguish between patients
      developing dementia and those with FMD and could aid the stratification of
      patients with memory problems.

PMID- 29319603
TI  - Population Neuroscience: Dementia Epidemiology Serving Precision Medicine and
      Population Health.
AB  - Over recent decades, epidemiology has made significant contributions to our
      understanding of dementia, translating scientific discoveries into population
      health. Here, we propose reframing dementia epidemiology as "population
      neuroscience," blending techniques and models from contemporary neuroscience with
      those of epidemiology and biostatistics. On the basis of emerging evidence and
      newer paradigms and methods, population neuroscience will minimize the bias
      typical of traditional clinical research, identify the relatively homogenous
      subgroups that comprise the general population, and investigate broader and
      denser phenotypes of dementia and cognitive impairment. Long-term follow-up of
      sufficiently large study cohorts will allow the identification of cohort effects
      and critical windows of exposure. Molecular epidemiology and omics will allow us
      to unravel the key distinctions within and among subgroups and better understand
      individuals' risk profiles. Interventional epidemiology will allow us to identify
      the different subgroups that respond to different treatment/prevention
      strategies. These strategies will inform precision medicine. In addition,
      insights into interactions between disease biology, personal and environmental
      factors, and social determinants of health will allow us to measure and track
      disease in communities and improve population health. By placing neuroscience
      within a real-world context, population neuroscience can fulfill its potential to
      serve both precision medicine and population health.

PMID- 29319604
TI  - The European Society of Regional Anaesthesia and Pain Therapy/American Society of
      Regional Anesthesia and Pain Medicine Recommendations on Local Anesthetics and
      Adjuvants Dosage in Pediatric Regional Anesthesia.
AB  - BACKGROUND AND OBJECTIVES: Dosage of local anesthetics (LAs) used for regional
      anesthesia in children is not well determined. In order to evaluate and come to a
      consensus regarding some of these controversial topics, The European Society of
      Regional Anaesthesia and Pain Therapy (ESRA) and the American Society of Regional
      Anesthesia and Pain Medicine (ASRA) developed a Joint Committee Practice Advisory
      on Local Anesthetics and Adjuvants Dosage in Pediatric Regional Anesthesia.
      METHODS: Representatives from both ASRA and ESRA composed the joint committee
      practice advisory. Evidence-based recommendations were based on a systematic
      search of the literature. In cases where no literature was available, expert
      opinion was elicited. RESULTS: Spinal anesthesia with bupivacaine can be
      performed with a dose of 1 mg/kg for newborn and/or infant and a dose of 0.5
      mg/kg in older children (>1 year of age). Tetracaine 0.5% is recommended for
      spinal anesthesia (dose, 0.07-0.13 mL/kg). Ultrasound-guided upper-extremity
      peripheral nerve blocks (eg, axillary, infraclavicular, interscalene,
      supraclavicular) in children can be performed successfully and safely using a
      recommended LA dose of bupivacaine or ropivacaine of 0.5 to 1.5 mg/kg.
      Dexmedetomidine can be used as an adjunct to prolong the duration of peripheral
      nerve blocks in children. CONCLUSIONS: High-level evidence is not yet available
      to guide dosage of LA used in regional blocks in children. The ASRA/ESRA
      recommendations intend to provide guidance in order to reduce the large
      variability of LA dosage currently observed in clinical practice.

PMID- 29319605
TI  - Epidural Hematoma Following Interlaminar Epidural Injection in Patient Taking
      Aspirin.
AB  - OBJECTIVE: We present a case report of a patient who developed an epidural
      hematoma following an interlaminar epidural steroid injection with no risk
      factors aside from old age and aspirin use for secondary prevention. CASE REPORT:
      A 79-year-old man developed an epidural hematoma requiring surgical treatment
      following an uncomplicated interlaminar epidural steroid injection performed for
      neurogenic claudication. In the periprocedural period, he continued aspirin for
      secondary prophylaxis following a myocardial infarction. CONCLUSIONS: For
      patients taking aspirin for primary or secondary prophylaxis, the American
      Society of Regional Anesthesia and Pain Medicine antiplatelet and anticoagulation
      guidelines for spine and pain procedures recommend a shared assessment and risk
      stratification when deciding to hold the medication for intermediate-risk
      neuraxial procedures. Cases such as this serve to highlight the importance of
      giving careful consideration to medical optimization of a patient even when a low
      or intermediate-risk procedure is planned.

PMID- 29319607
TI  - Longitudinal resting-state functional magnetic resonance imaging in a mouse model
      of metastatic bone cancer reveals distinct functional reorganizations along a
      developing chronic pain state.
AB  - Functional neuroimaging has emerged as attractive option for characterizing pain
      states complementing behavioral readouts or clinical assessment. In particular,
      resting-state functional magnetic resonance imaging (rs-fMRI) enables monitoring
      of functional adaptations across the brain, for example, in response to chronic
      nociceptive input. We have used rs-fMRI in a mouse model of chronic pain from
      breast cancer-derived tibial bone metastases to identify pain-induced alterations
      in functional connectivity. Combined assessment of behavioral readouts allowed
      for defining a trajectory as model function for extracting pain-specific
      functional connectivity changes from the fMRI data reflective of a chronic pain
      state. Cingulate and prefrontal cortices as well as the ventral striatum were
      identified as predominantly affected regions, in line with findings from clinical
      and preclinical studies. Inhibition of the peripheral bone remodeling processes
      by antiosteolytic therapy led to a reduction of pain-induced network alterations,
      emphasizing the specificity of the functional readouts for a developing chronic
      pain state.

PMID- 29319606
TI  - Disruption of nNOS-NOS1AP protein-protein interactions suppresses neuropathic
      pain in mice.
AB  - Elevated N-methyl-D-aspartate receptor (NMDAR) activity is linked to central
      sensitization and chronic pain. However, NMDAR antagonists display limited
      therapeutic potential because of their adverse side effects. Novel approaches
      targeting the NR2B-PSD95-nNOS complex to disrupt signaling pathways downstream of
      NMDARs show efficacy in preclinical pain models. Here, we evaluated the
      involvement of interactions between neuronal nitric oxide synthase (nNOS) and the
      nitric oxide synthase 1 adaptor protein (NOS1AP) in pronociceptive signaling and
      neuropathic pain. TAT-GESV, a peptide inhibitor of the nNOS-NOS1AP complex,
      disrupted the in vitro binding between nNOS and its downstream protein partner
      NOS1AP but not its upstream protein partner postsynaptic density 95 kDa (PSD95).
      Putative inactive peptides (TAT-cp4GESV and TAT-GESVDelta1) failed to do so. Only
      the active peptide protected primary cortical neurons from glutamate/glycine
      induced excitotoxicity. TAT-GESV, administered intrathecally (i.t.), suppressed
      mechanical and cold allodynia induced by either the chemotherapeutic agent
      paclitaxel or a traumatic nerve injury induced by partial sciatic nerve ligation.
      TAT-GESV also blocked the paclitaxel-induced phosphorylation at Ser15 of p53, a
      substrate of p38 MAPK. Finally, TAT-GESV (i.t.) did not induce NMDAR-mediated
      motor ataxia in the rotarod test and did not alter basal nociceptive thresholds
      in the radiant heat tail-flick test. These observations support the hypothesis
      that antiallodynic efficacy of an nNOS-NOS1AP disruptor may result, at least in
      part, from blockade of p38 MAPK-mediated downstream effects. Our studies
      demonstrate, for the first time, that disrupting nNOS-NOS1AP protein-protein
      interactions attenuates mechanistically distinct forms of neuropathic pain
      without unwanted motor ataxic effects of NMDAR antagonists.

PMID- 29319608
TI  - Novel approach to characterising individuals with low back-related leg pain:
      cluster identification with latent class analysis and 12-month follow-up.
AB  - Traditionally, low back-related leg pain (LBLP) is diagnosed clinically as
      referred leg pain or sciatica (nerve root involvement). However, within the
      spectrum of LBLP, we hypothesised that there may be other unrecognised patient
      subgroups. This study aimed to identify clusters of patients with LBLP using
      latent class analysis and describe their clinical course. The study population
      was 609 LBLP primary care consulters. Variables from clinical assessment were
      included in the latent class analysis. Characteristics of the statistically
      identified clusters were compared, and their clinical course over 1 year was
      described. A 5 cluster solution was optimal. Cluster 1 (n = 104) had mild leg
      pain severity and was considered to represent a referred leg pain group with no
      clinical signs, suggesting nerve root involvement (sciatica). Cluster 2 (n =
      122), cluster 3 (n = 188), and cluster 4 (n = 69) had mild, moderate, and severe
      pain and disability, respectively, and response to clinical assessment items
      suggested categories of mild, moderate, and severe sciatica. Cluster 5 (n = 126)
      had high pain and disability, longer pain duration, and more comorbidities and
      was difficult to map to a clinical diagnosis. Most improvement for pain and
      disability was seen in the first 4 months for all clusters. At 12 months, the
      proportion of patients reporting recovery ranged from 27% for cluster 5 to 45%
      for cluster 2 (mild sciatica). This is the first study that empirically shows the
      variability in profile and clinical course of patients with LBLP including
      sciatica. More homogenous groups were identified, which could be considered in
      future clinical and research settings.

PMID- 29319609
TI  - Joint nociceptor nerve activity and pain in an animal model of acute gout and its
      modulation by intra-articular hyaluronan.
AB  - The mechanisms whereby deposition of monosodium urate (MSU) crystals in gout
      activates nociceptors to induce joint pain are incompletely understood. We tried
      to reproduce the signs of painful gouty arthritis, injecting into the knee joint
      of rats suspensions containing amorphous or triclinic, needle MSU crystals. The
      magnitude of MSU-induced inflammation and pain behavior signs were correlated
      with the changes in firing frequency of spontaneous and movement-evoked nerve
      impulse activity recorded in single knee joint nociceptor saphenous nerve fibers.
      Joint swelling, mechanical and cold allodynia, and hyperalgesia appeared 3 hours
      after joint injection of MSU crystals. In parallel, spontaneous and movement
      evoked joint nociceptor impulse activity raised significantly. Solutions
      containing amorphous or needle-shaped MSU crystals had similar inflammatory and
      electrophysiological effects. Intra-articular injection of hyaluronan (HA,
      Synvisc), a high-MW glycosaminoglycan present in the synovial fluid with
      analgesic effects in osteoarthritis, significantly reduced MSU-induced behavioral
      signs of pain and decreased the enhanced joint nociceptor activity. Our results
      support the interpretation that pain and nociceptor activation are not triggered
      by direct mechanical stimulation of nociceptors by MSU crystals, but are
      primarily caused by the release of excitatory mediators by inflammatory cells
      activated by MSU crystals. Intra-articular HA decreased behavioral and
      electrophysiological signs of pain, possibly through its viscoelastic filtering
      effect on the mechanical forces acting over sensitized joint sensory endings and
      probably also by a direct interaction of HA molecules with the transducing
      channels expressed in joint nociceptor terminals.

PMID- 29319610
TI  - The effectiveness of online pain resources for health professionals: a systematic
      review with subset meta-analysis of educational intervention studies.
AB  - Online educational interventions are increasingly developed for health
      professionals and students, although graduate and undergraduate medical curricula
      often contain limited information about how to assess and manage pain. This study
      reviews the literature on the effectiveness of pain-related online educational
      resources. Studies were identified through a search of Medline, PsychINFO, Web of
      Science, CINAHL, PubMed, Scopus, Cochrane Library, Google Scholar, and OpenGrey
      databases. Search terms included 3 concept blocks: (1) type of intervention
      online education, computer-based, e-learning, web-based, and internet-based; (2)
      population-pediatrician, physician, nurse, psychologist, and medical; and (3)
      outcome-pain*. Thirty-two studies (13 randomised controlled trials, 5
      nonrandomised controlled trials, and 14 single-group pre-post studies) were
      included. Ten provided data for inclusion in a series of between-groups meta
      analyses. After intervention, participants receiving online instruction had
      significantly greater knowledge compared with those receiving training as
      usual/alternative training (Hedges' g = 0.80, 95% confidence interval [CI]: 0.12
      1.49), and students had significantly greater skills compared with students
      receiving training as usual (g = 1.34, CI: 0.38-2.30). No significant differences
      were found for confidence/competence (g = 0.02, CI: -0.79 to 0.84) or
      attitudes/beliefs (g = 0.16, CI: -0.48 to 0.79). Although online educational
      resources show promise in improving learner knowledge, considerable heterogeneity
      exists between studies in quality, design, educational content, and outcomes.
      Furthermore, methodologically robust RCTs are required to establish the
      effectiveness of online educational interventions and a greater understanding of
      the key features of successful online resources, including cognitive
      interactivity. Few studies assessed health outcomes for patients, remaining a
      major priority for future investigations.

PMID- 29319611
TI  - Comparison of somatosensory cortex excitability between migraine and "strict
      criteria" tension-type headache: a magnetoencephalographic study.
AB  - Tension-type headache (TTH) and migraine are both common types of headaches.
      Despite distinct symptoms, TTH and migraine are highly comorbid and exhibit many
      clinical similarities. This study enrolled consecutive patients with TTH and age-
      and sex-matched patients with migraine and healthy controls to investigate
      whether TTH and migraine are similar in brain excitability change assessed by
      magnetoencephalography. Patients with TTH were excluded if they reported any
      headache features or associated symptoms of migraine. In response to paired-pulse
      electrical stimulations, the gating responses obtained from the contralateral
      primary somatosensory cortex differed between groups. The first response, which
      reflected the preactivation excitability, was smaller in the migraine group
      (29.54 +/- 2.31 pAm) compared with the TTH group (79.76 +/- 8.36, P < 0.001) and
      controls (59.95 +/- 4.26, P = 0.006). The gating ratio (ie, the ratio of the
      second vs first response strength) was 0.76 +/- 0.03 in controls, 0.88 +/- 0.03
      in the migraine group, 0.93 +/- 0.03 in the TTH group, with a significant
      increase in TTH (P = 0.003 vs controls) suggesting central disinhibition. The
      area under the receiver operating characteristic curve of the first response
      strength in differentiating between TTH and migraine was 0.85 +/- 0.44,
      indicating excellent discrimination. In conclusion, TTH and migraine are
      different clinical entities in view of somatosensory cortex excitability. The
      preactivation excitability assessed through somatosensory gating is a potential
      marker for differentiating between TTH and migraine.

PMID- 29319612
TI  - Mitigating Risk of Immunosuppression by Immune Monitoring: Are We There?

PMID- 29319613
TI  - Cell Therapy for Severe Hemophilia: Study Has Come Full Circle.

PMID- 29319614
TI  - Necessity of Interrupted Time Series Analysis in Evaluating the Impact of PHS
      Risk Identification and Introduction of Direct-Acting Antiviral Therapy and Share
      35 Implementation.

PMID- 29319615
TI  - Clinical and Pathological Features of Plasma Cell-Rich Acute Rejection After
      Kidney Transplantation.
AB  - BACKGROUND: Plasma cell-rich acute rejection (PCAR) is a rare type of allograft
      rejection characterized by the presence of mature plasma cells. In general, the
      prognosis of PCAR is poor, and its clinical and pathological features remain
      unclear. METHODS: We performed a retrospective observational study and compared
      allograft survival between kidney transplant recipients who developed PCAR and
      those who did not develop PCAR. We further analyzed clinical and pathological
      risk factors for allograft failure in PCAR patients. RESULTS: Of 1956 recipients,
      40 developed PCAR. There was a higher prevalence of deceased donor transplants
      (27.5% vs 11.7%, P = 0.0059), longer median total ischemia time (99 minutes;
      interquartile range, 71-144 vs 77 minutes; interquartile range, 59-111; P =
      0.0309), and lower prevalence of ABO-incompatible transplantation (7.5% vs 22.5%;
      P = 0.0206) in patients with PCAR than in those without PCAR.Multivariate Cox
      regression analysis showed that development of PCAR was associated with allograft
      loss (hazard ratio, 8.03; 95% confidence interval, 3.89-14.80; P < 0.0001).We
      classified PCAR according to the Banff 2015 criteria into a borderline change
      group, a T cell-mediated rejection (TCMR) group, an antibody-mediated rejection
      (AMR) or suspected of having AMR (AMR/sAMR) group, and a mixed rejection
      (TCMR/AMR) group. The AMR/sAMR group was associated with a lower rate of
      allograft survival without significant difference (log-rank test, P = 0.1692).
      CONCLUSIONS: The results indicated that PCAR was an independent risk factor for
      allograft loss. PCAR presented with all types of rejection in the Banff 2015
      criteria, and AMR/sAMR was associated with poor allograft survival.

PMID- 29319616
TI  - Preserving Treg Function: Beyond mTOR Inhibitors.

PMID- 29319617
TI  - Biomarkers and Kidney Transplant: Time for a New Paradigm?

PMID- 29319618
TI  - Effect of Conversion to CTLA4Ig on Tacrolimus-Induced Diabetic Rats.
AB  - BACKGROUND: The effect of conversion to cytotoxic T lymphocyte-associated protein
      4 immunoglobulin (CTLA4Ig) treatment on tacrolimus (TAC)-induced renal
      dysfunction is well known, but its effect on TAC-induced diabetes mellitus (DM)
      is still undetermined. In the present study, we tested the diabetogenicity of
      CTLA4Ig and evaluated the effect of conversion to CTLA4Ig treatment on TAC
      induced diabetic rats. METHODS: We tested diabetogenicity of CTLA4Ig by
      escalating doses (0.25, 0.5, 1, 2, and 4 mg/kg weekly) for 4 weeks. In the
      conversion study, we administered TAC (1.5 mg/kg) for 3 weeks and confirmed TAC
      induced DM by intraperitoneal glucose tolerance test. Thereafter, TAC
      administration was continued, withdrawn, or replaced by CTLA4Ig treatment (1 or 2
      mg/kg) for additional 3 weeks. The effect of CTLA4Ig on TAC-induced DM in vivo
      and in vitro was evaluated by assessing pancreatic islet function,
      histopathology, oxidative stress, apoptosis, and macrophage infiltration.
      RESULTS: Intraperitoneal glucose tolerance test in the CTLA4Ig groups did not
      differ from the control group. In addition, plasma insulin level, glucose-induced
      insulin secretion, and islet viability were not different between the CTLA4Ig and
      control groups. In the conversion study, TAC withdrawal ameliorated pancreatic
      islet dysfunction compared with the TAC group, and conversion to CTLA4Ig further
      improved pancreatic islet function compared with the TAC withdrawal group. TAC
      induced oxidative stress, apoptotic cell death, and infiltration of macrophages
      decreased with TAC withdrawal, and CTLA4Ig conversion further reduced those
      values. In the in vitro study, CTLA4Ig decreased TAC-induced pancreatic islet
      cell death and reactive oxygen species production. CONCLUSIONS: CTLA4Ig was not
      diabetogenic, and conversion to CTLA4Ig reduced TAC-induced pancreatic islet
      injury.

PMID- 29319619
TI  - History of Marijuana Use Does Not Affect Outcomes on the Liver Transplant
      Waitlist.
AB  - BACKGROUND: Data are limited on marijuana use and its impact on liver transplant
      (LT) waitlist outcomes. We aimed to assess the risk of waitlist
      mortality/delisting and likelihood of LT among prior marijuana users and to
      determine the prevalence and factors associated with marijuana use. METHODS:
      Retrospective cohort of adults evaluated for LT over 2 years at a large LT
      center. Marijuana use was defined by self-report in psychosocial assessment
      and/or positive urine toxicology. Ongoing marijuana use was not permitted for LT
      listing during study period. RESULTS: Eight hundred eighty-four adults were
      evaluated, and 585 (66%) were listed for LT (median follow-up, 1.4 years;
      interquartile range, 0.5-2.0). Prevalence of marijuana use was 48%, with 7% being
      recent users and 41% prior users. Marijuana use had statistically significant
      association with alcoholic cirrhosis (incidence rate ratio [IRR], 1.9) and
      hepatitis C (IRR, 2.1) versus hepatitis B, tobacco use (prior IRR, 1.4; recent
      IRR, 1.3 vs never), alcohol use (never IRR 0.1; heavy use/abuse IRR 1.2 vs
      social), and illicit drug use (prior IRR, 2.3; recent, 1.9 vs never). In adjusted
      competing risk regression, marijuana use was not associated with the probability
      of LT (prior hazard ratio [HR], 0.9; recent HR, 0.9 vs never) or waitlist
      mortality/delisting (prior HR, 1.0; recent HR, 1.0 vs never). However, recent
      illicit drug use was associated with higher risk of death or delisting (HR, 1.8;
      P = 0.004 vs never). CONCLUSIONS: Unlike illicit drug use, marijuana use was not
      associated with worse outcomes on the LT waitlist. Prospective studies are needed
      to assess ongoing marijuana use on the LT waitlist and post-LT outcomes.

PMID- 29319620
TI  - Liver Transplantation for NASH-Related Hepatocellular Carcinoma Versus Non-NASH
      Etiologies of Hepatocellular Carcinoma.
AB  - BACKGROUND: Liver transplant (LT) for nonalcoholic steatohepatitis (NASH) related
      hepatocellular carcinoma (HCC) is not well characterized in the literature. The
      aim of the study was to examine characteristics and outcomes of patients who had
      LT for NASH-HCC (NASH) versus HCC from other liver diseases (non-NASH). METHODS:
      Using a 2-center retrospective design, all patients from 2004 to 2014 that
      received LT for HCC were analyzed. Subgroup analysis stratified patients
      according to Milan criteria. RESULTS: Nine hundred twenty-nine patients were
      transplanted for HCC. Sixty (6.5%) of 929 had HCC in the context of NASH. There
      were no significant differences between groups for pretransplant or explant tumor
      characteristics. The actuarial 1-, 3- and 5-year overall survival was 98%, 96%,
      and 80% in NASH versus 95%, 84%, and 78% in non-NASH (P = 0.1). No differences in
      tumor recurrence were observed in patients within and beyond Milan in the NASH
      group. Multivariate Cox regression demonstrated NASH status to be a protective
      factor for recurrence among patients with tumors beyond Milan (hazard ratio,
      0.21; 95% confidence interval, 0.05-0.86; P = 0.029). CONCLUSION: After LT,
      outcomes are similar between NASH and non-NASH etiologies for HCC. The hypothesis
      that patients with more advanced HCC tumors in the context of NASH may have more
      favorable outcomes after LT has been generated, but requires further study.

PMID- 29319621
TI  - Selective CD28 Inhibition Modulates Alloimmunity and Cardiac Allograft
      Vasculopathy in Anti-CD154-Treated Monkeys.
AB  - BACKGROUND: Selective CD28 inhibition is actively pursued as an alternative to B7
      blockade using cytotoxic T lymphocyte antigen 4 Ig based on the hypothesis that
      the checkpoint immune regulators cytotoxic T lymphocyte antigen 4 and programmed
      death ligand 1 will induce tolerogenic immune signals. We previously showed that
      blocking CD28 using a monovalent nonactivating reagent (single-chain anti-CD28 Fv
      fragment linked to alpha-1 antitrypsin [sc28AT]) synergizes with calcineurin
      inhibitors in nonhuman primate (NHP) kidney and heart transplantation. Here, we
      explored the efficacy of combining a 3-week "induction" sc28AT treatment with
      prolonged CD154 blockade. METHODS: Cynomolgus monkey heterotopic cardiac
      allograft recipients received sc28AT (10 mg/kg, d0-20, n = 3), hu5C8 (10-30
      mg/kg, d0-84, n = 4), or combination (n = 6). Graft survival was monitored by
      telemetry. Protocol biopsies and graft explants were analyzed for International
      Society of Heart and Lung Transplantation acute rejection grade and cardiac
      allograft vasculopathy score. Alloantibody, T-cell phenotype and regulatory T
      cells were analyzed by flow cytometry. Immunochemistry and gene expression
      (NanoString) characterized intra-graft cellular infiltration. RESULTS: Relative
      to modest prolongation of median graft survival time with sc28AT alone (34 days),
      hu5C8 (133 days), and sc28AT + hu5C8 (141 days) prolonged survival to a similar
      extent. CD28 blockade at induction, added to hu5C8, significantly attenuated the
      severity of acute rejection and cardiac allograft vasculopathy during the first 3
      months after transplantation relative to hu5C8 alone. These findings were
      associated with decreased proportions of circulating CD8 and CD3CD28 T cells, and
      modulation of inflammatory gene expression within allografts. CONCLUSIONS:
      Induction with sc28AT promotes early cardiac allograft protection in hu5C8
      treated NHPs. These results support further investigation of prolonged selective
      CD28 inhibition with CD40/CD154 blockade in NHP transplants.

PMID- 29319622
TI  - A High Portal Venous Pressure Gradient Increases Gut-Related Bacteremia and
      Consequent Early Mortality After Living Donor Liver Transplantation.
AB  - BACKGROUND: Portal hypertension (PHT) is defined as a portal venous pressure
      gradient (PVPG) exceeding 5 mm Hg, which results in severe clinical
      manifestations. However, the validity of intraoperative PVPG monitoring and the
      association between PHT and bacterial translocation after liver transplantation
      remain unclear. METHODS: In this retrospective study, 223 patients who underwent
      primary adult-to-adult living donor liver transplantation from 2008 to 2015 were
      divided into 2 groups based on the PVPG at the end of the operation: high PVPG
      (>5 mm Hg, n = 69) and low PVPG (<=5 mm Hg, n = 154). The clinical factors were
      compared between the groups, and the association between a high PVPG and
      posttransplant bacteremia/bacterial infections was investigated. RESULTS: The
      high PVPG group had a significantly higher incidence of bacteremia (46% vs 24%, P
      < 0.001), higher 90-day mortality rate (20% vs 7%, P = 0.002), and poorer 1-year
      survival (71% vs 86%, P = 0.006). The high PVPG group had a particularly higher
      incidence of bacteremia caused by "gut bacteria" including Enterobacteriaceae,
      Bacteroides spp., and Enterococcus spp. (29% vs 12%, P = 0.003). Multivariate
      analysis showed that a PVPG greater than 5 mm Hg (odds ratio, 2.55; 95%
      confidence interval, 1.18-5.55; P = 0.017) was an independent predictor of
      bacteremia due to gut bacteria. CONCLUSIONS: Monitoring of the PVPG is clinically
      meaningful for predicting patients' prognosis. In particular, a high PVPG with a
      threshold of 5 mm Hg at the end of adult-to-adult living donor liver
      transplantation may increase gut-related bacteremia through the mechanism of
      bacterial translocation, resulting in early mortality.

PMID- 29319623
TI  - B Cells in Transplantation of Rat, Mouse, and Man.

PMID- 29319624
TI  - Long-term Outcome of 1-step Kidney Transplantation and Bladder Augmentation
      Procedure in Pediatric Patients.
AB  - BACKGROUND: Guidelines for bladder augmentation (BA) in kidney transplantation
      (KT) recipients are not well-defined. In our center, simultaneous BA with KT (BA
      KT) is performed. We assessed transplantation outcomes of this unique extensive
      procedure. METHODS: A case-control single center retrospective study.
      Transplantation outcomes were compared with those of KT recipients who did not
      need BA. RESULTS: Compared with 22 patients who underwent KT only, for 9 who
      underwent BA-KT, surgical complications and the need for revision in the early
      posttransplantation period were similar; early graft function was better:
      estimated glomerular filtration rate, 96.5 +/- 17.1 versus 79.4 +/- 16.6 mL/min
      at 0 to 6 months (P = 0.02); posttransplantation clean intermittent
      catheterization was more often needed: by 78% (7/9) versus 13% (3/22); and
      asymptomatic bacteriuria was more common: 100% versus 9% during the first 6
      months (P < 0.001), 55% versus 9% (P = 0.02) and 66.6% versus 9% during the first
      and second years, respectively (P = 0.004). Urinary tract infection (UTI)
      incidence was also higher: 100% versus 23% during the first 6 months and 44%
      versus 9% during the second year posttransplantation. Graft function deteriorated
      significantly in the BA-KT group by the fifth posttransplantation year: estimated
      glomerular filtration rate was 47.7 +/- 39.7 mL/min versus 69 +/- 21.3 mL/min,
      with only 6 (66%) of 9 functioning grafts versus 100% in the KT only group.
      Causes of graft loss were noncompliance with drug therapy in 2 patients and
      recurrent UTIs in 2 patients. CONCLUSIONS: Excellent short-term outcome for
      simultaneous BA-KT is threatened by graft loss due to a high prevalence of UTIs
      and patient noncompliance with the demanding complex posttransplantation therapy.

PMID- 29319625
TI  - Early Hospital Readmission: The Canary in the Coal Mine?

PMID- 29319626
TI  - Publication Rates of Oral Abstract Presentations at the 2014 International
      Congress of The Transplantation Society.

PMID- 29319627
TI  - Opioid Prescription, Morbidity, and Mortality in US Transplant Recipients.
AB  - BACKGROUND: Centers for Disease Control and Prevention guidelines recommend
      caution in prescribing opioids for chronic pain. The characteristics of opioid
      prescription (OpRx) among kidney transplant (KTx) recipients have not been
      described in a national population. METHODS: We assessed OpRx prevalence among
      prevalent KTx recipients, and associated duration (long-term, defined as >=90
      days in a year) and dosing (in morphine milligram equivalents per day of <50, 50
      89, and >=90) with outcomes, death and graft loss, among incident KTx recipients
      using 2006-2010 US Renal Data System files, including Medicare Part D for
      medication ascertainment. Cox models controlled for recipient factors. RESULTS:
      Of 36,486 KTx recipients in the 2010 prevalent cohort, approximately 14.6% had
      long-term OpRx. The strongest association with long-term OpRx after KTx was long
      term OpRx before KTx (64%; adjusted odds ratio, 95% confidence interval, 95.2,
      74.2-122.1). Incident KTx recipients with long-term OpRx had increased risk of
      mortality and graft loss compared with those without OpRx or short-term OpRx
      after KTx. This risk was highest among recipients with long-term OpRx doses of
      >=90 morphine milligram equivalents or higher per day (adjusted hazard ratio, 95%
      confidence interval, 1.61, 1.24-2.10 for death, and 1.33, 1.05-1.67 for graft
      loss, respectively). CONCLUSIONS: In contrast to either no or short-term OpRx,
      long-term, and especially long-term high-dose OpRx, is associated with increased
      risk of death and graft loss in US KTx recipients. Causal relationships cannot be
      inferred, and OpRx may be an illness marker. Nevertheless, efforts to treat pain
      effectively in KTx recipients with less toxic interventions and decrease OpRx
      deserve consideration.

PMID- 29319628
TI  - Heart Transplantation in a Left Ventricular Assist Device Recipient After Donor's
      Extracorporeal Membrane Oxygenation Support: Is It Safe?

PMID- 29319629
TI  - Patterns of Discordance Between Pretransplant Imaging Stage of Hepatocellular
      Carcinoma and Posttransplant Pathologic Stage: A Contemporary Appraisal of the
      Milan Criteria.
AB  - BACKGROUND: Patients with hepatocellular carcinoma (HCC) exceeding Milan criteria
      on explant pathology are at increased risk of recurrence and death. Discordance
      between contemporary magnetic resonance imaging (MRI) and explant pathology, and
      preoperative characteristics predictive of discordance are not well understood.
      METHODS: Patients who underwent orthotopic liver transplantation for HCC after
      preoperative MRI were identified in a prospectively collected institutional
      database (January 2003 to December 2013). Patients were dichotomized to "within"
      or "outside" Milan criteria by both imaging and explant pathologic evaluation.
      Binary logistic regression and Kaplan-Meier methodology were used to identify
      independent predictors of imaging/pathologic discordance and its impact on
      posttransplant survival. RESULTS: Of 318 patients with HCC meeting Milan criteria
      by MRI at the time of orthotopic liver transplantation, 248 (78.0%) remained
      within a pathological correlate of Milan criteria on explant examination.
      Understaging was associated with worse median recurrence-free survival (64.0
      months vs 140.0 months, P = 0.002) and overall survival (96.0 months vs 143.0
      months, P = 0.005), and did not vary between patients exceeding criteria due to
      tumor explant greater than 5 cm, more than 3 tumor foci, or a tumor greater than
      3 cm in the setting of multifocality. Discordance was independently associated
      with an increasing serum alpha fetal protein level (odds ratio, 2.82; 95%
      confidence interval, 1.37-5.79; P = 0.005). CONCLUSIONS: Underestimating HCC
      burden before liver transplant remains frequent despite contemporary imaging
      technologies. Patients with an increasing alpha fetal protein before
      transplantation may benefit from more frequent testing or novel neoadjuvant
      therapies.

PMID- 29319630
TI  - Exposure to Ambient Ultrafine Particles and Nitrogen Dioxide and Incident
      Hypertension and Diabetes.
AB  - BACKGROUND: Previous studies reported that long-term exposure to traffic-related
      air pollution may increase the incidence of hypertension and diabetes. However,
      little is known about the associations of ultrafine particles (<=0.1 MUm in
      diameter) with these two conditions. METHODS: We conducted a population-based
      cohort study to investigate the associations between exposures to ultrafine
      particles and nitrogen dioxide (NO2) and the incidence of diabetes and
      hypertension. Our study population included all Canadian-born residents aged 30
      to 100 years who lived in the City of Toronto, Canada, from 1996 to 2012.
      Outcomes were ascertained using validated province-wide databases. We estimated
      annual concentrations of ultrafine particles and NO2 using land-use regression
      models and assigned these estimates to participants' annual postal code addresses
      during the follow-up period. Using random-effects Cox proportional hazards
      models, we calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for
      ultrafine particles and NO2, adjusted for individual- and neighborhood-level
      covariates. We considered both single- and multipollutant models. RESULTS: Each
      interquartile change in exposure to ultrafine particles was associated with
      increased risk of incident hypertension (HR = 1.03; 95% CI = 1.02, 1.04) and
      diabetes (HR = 1.06; 95% CI = 1.05, 1.08) after adjusting for all covariates.
      These results remained unaltered with further control for fine particulate matter
      (<=2.5 MUm; PM2.5) and NO2. Similarly, NO2 was positively associated with
      incident diabetes (HR = 1.06; 95% CI = 1.05, 1.07) after controlling for
      ultrafine particles and PM2.5. CONCLUSIONS: Exposure to traffic-related air
      pollution including ultrafine particles and NO2 may increase the risk for
      incident hypertension and diabetes. See video abstract at,
      http://links.lww.com/EDE/B337.

PMID- 29319631
TI  - A Practical Example Demonstrating the Utility of Single-world Intervention
      Graphs.

PMID- 29319632
TI  - Extracorporeal Membrane Oxygenation for Pertussis: Predictors of Outcome
      Including Pulmonary Hypertension and Leukodepletion.
AB  - OBJECTIVE: The recent increase of pertussis cases worldwide has generated
      questions regarding the utility of extracorporeal membrane oxygenation for
      children with pertussis. We aimed to evaluate factors associated with
      extracorporeal membrane oxygenation outcome. DESIGN: The study was designed in
      two parts: a retrospective analysis of the Extracorporeal Life Support
      Organization Registry to identify factors independently linked to outcome, and an
      expanded dataset from individual institutions to examine the association of WBC
      count, pulmonary hypertension, and leukodepletion with survival. SETTING:
      Extracorporeal Life Support Organization Registry database from 2002 though 2015,
      and contributions from 19 international centers. PATIENTS: Two hundred infants
      from the Extracorporeal Life Support Organization Registry and expanded data on
      73 children. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 200
      infants who received extracorporeal membrane oxygenation for pertussis, only 56
      survived (28%). In a multivariable logistic regression analysis, the following
      variables were independently associated with increased chance of survival: older
      age (odds ratio, 1.43 [1.03-1.98]; p = 0.034), higher PaO2/FIO2 ratio (odds
      ratio, 1.10 [1.03-1.17]; p = 0.003), and longer intubation time prior to the
      initiation of extracorporeal membrane oxygenation (odds ratio, 2.10 [1.37-3.22];
      p = 0.001). The use of vasoactive medications (odds ratio, 0.33 [0.11-0.99]; p =
      0.047), and renal neurologic or infectious complications (odds ratio, 0.21 [0.08
      0.56]; p = 0.002) were associated with increased mortality. In the expanded
      dataset (n =73), leukodepletion was independently associated with increased
      chance of survival (odds ratio, 3.36 [1.13-11.68]; p = 0.03) while the presence
      of pulmonary hypertension was adverse (odds ratio, 0.06 [0.01-0.55]; p = 0.01).
      CONCLUSIONS: The survival rate for infants with pertussis who received
      extracorporeal membrane oxygenation support remains poor. Younger age, lower
      PaO2/FIO2 ratio, vasoactive use, pulmonary hypertension, and a rapidly
      progressive course were associated with increased mortality. Our results suggest
      that pre-extracorporeal membrane oxygenation leukodepletion may provide a
      survival advantage.

PMID- 29319633
TI  - Risk Factors for Healthcare-Associated Infections After Pediatric Cardiac
      Surgery.
AB  - OBJECTIVES: Healthcare-associated infections after pediatric cardiac surgery are
      significant causes of morbidity and mortality. We aimed to identify the risk
      factors for the occurrence of healthcare-associated infections after pediatric
      cardiac surgery. DESIGN: Retrospective, single-center observational study.
      SETTING: PICU at a tertiary children's hospital. PATIENTS: Consecutive pediatric
      patients less than or equal to 18 years old admitted to the PICU after cardiac
      surgery, between January 2013 and December 2015. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: All the data were retrospectively collected from
      the medical records of patients. We assessed the first surgery during a single
      PICU stay and identified four common healthcare-associated infections, including
      bloodstream infection, surgical site infection, pneumonia, and urinary tract
      infection, according to the definitions of the Centers for Disease Control and
      Prevention and National Healthcare Safety Network. We assessed the pre-, intra-,
      and early postoperative potential risk factors for these healthcare-associated
      infections via multivariable analysis. In total, 526 cardiac surgeries (394
      patients) were included. We identified 81 cases of healthcare-associated
      infections, including, bloodstream infections (n = 30), surgical site infections
      (n = 30), urinary tract infections (n = 13), and pneumonia (n = 8). In the case
      of 71 of the surgeries (13.5%), at least one healthcare-associated infection was
      reported. Multivariable analysis indicated the following risk factors for
      postoperative healthcare-associated infections: mechanical ventilation greater
      than or equal to 3 days (odds ratio, 4.81; 95% CI, 1.89-12.8), dopamine use (odds
      ratio, 3.87; 95% CI, 1.53-10.3), genetic abnormality (odds ratio, 2.53; 95% CI,
      1.17-5.45), and delayed sternal closure (odds ratio, 3.78; 95% CI, 1.16-12.8).
      CONCLUSIONS: Mechanical ventilation greater than or equal to 3 days, dopamine
      use, genetic abnormality, and delayed sternal closure were associated with
      healthcare-associated infections after pediatric cardiac surgery. Since the use
      of dopamine is an easily modifiable risk factor, and may serve as a potential
      target to reduce healthcare-associated infections, further studies are needed to
      establish whether dopamine negatively impacts the development of healthcare
      associated infections.

PMID- 29319634
TI  - Hyperoxia and Hypocapnia During Pediatric Extracorporeal Membrane Oxygenation:
      Associations With Complications, Mortality, and Functional Status Among
      Survivors.
AB  - OBJECTIVES: To determine the frequency of hyperoxia and hypocapnia during
      pediatric extracorporeal membrane oxygenation and their relationships to
      complications, mortality, and functional status among survivors. DESIGN:
      Secondary analysis of data collected prospectively by the Collaborative Pediatric
      Critical Care Research Network. SETTING: Eight Collaborative Pediatric Critical
      Care Research Network-affiliated hospitals. PATIENTS: Age less than 19 years and
      treated with extracorporeal membrane oxygenation. INTERVENTIONS: Hyperoxia was
      defined as highest PaO2 greater than 200 Torr (27 kPa) and hypocapnia as lowest
      PaCO2 less than 30 Torr (3.9 kPa) during the first 48 hours of extracorporeal
      membrane oxygenation. Functional status at hospital discharge was evaluated among
      survivors using the Functional Status Scale. MEASUREMENTS AND MAIN RESULTS: Of
      484 patients, 420 (86.7%) had venoarterial extracorporeal membrane oxygenation
      and 64 (13.2%) venovenous; 69 (14.2%) had extracorporeal membrane oxygenation
      initiated during cardiopulmonary resuscitation. Hyperoxia occurred in 331 (68.4%)
      and hypocapnia in 98 (20.2%). Hyperoxic patients had higher mortality than
      patients without hyperoxia (167 [50.5%] vs 48 [31.4%]; p < 0.001), but no
      difference in functional status among survivors. Hypocapnic patients were more
      likely to have a neurologic event (49 [50.0%] vs 143 (37.0%]; p = 0.021) or
      hepatic dysfunction (49 [50.0%] vs 121 [31.3%]; p < 0.001) than patients without
      hypocapnia, but no difference in mortality or functional status among survivors.
      On multivariable analysis, factors independently associated with increased
      mortality included highest PaO2 and highest blood lactate concentration in the
      first 48 hours of extracorporeal membrane oxygenation, congenital diaphragmatic
      hernia, and being a preterm neonate. Factors independently associated with lower
      mortality included meconium aspiration syndrome. CONCLUSIONS: Hyperoxia is common
      during pediatric extracorporeal membrane oxygenation and associated with
      mortality. Hypocapnia appears to occur less often and although associated with
      complications, an association with mortality was not observed.

PMID- 29319635
TI  - Low-Dose Epinephrine Boluses for Acute Hypotension in the PICU.
AB  - OBJECTIVES: To describe the use of low-dose bolus epinephrine in critically ill
      children during an acute hypotensive episode or prearrest condition. DESIGN:
      Institutional Review Board approved, single-center, retrospective medical chart
      review. SETTING: Large medical-surgical PICU within a freestanding, tertiary care
      children's hospital. PATIENTS: Patients admitted to the PICU between June 1,
      2015, and June 1, 2016, who received low-dose (<= 5 ug/kg) IV bolus epinephrine.
      INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Twenty-four resuscitation
      episodes (63 doses; 19 patients) were analyzed. Median age and weight of patients
      were 9 years (interquartile range, 1-15 yr) and 38.5 kg (interquartile range, 12
      54.8 kg). Median Pediatric Risk of Mortality III score was 17 (interquartile
      range, 10-27). Mean epinephrine dose was 1.3 +/- 1.1 ug/kg. Median number of
      doses per patient was two. If more than one dose was provided, median dosing
      interval was 6.5 minutes. Heart rate and mean arterial blood pressure were
      compared at the time of epinephrine administration and 1-4 minutes (median = 1
      min) following administration. Heart rate changed from 130 +/- 41 to 150 +/- 33
      beats/min (p < 0.05), and mean arterial blood pressure changed from 51 +/- 17 to
      75 +/- 27 mm Hg (p < 0.001). Variability in mean arterial blood pressure response
      was observed; nonresponders required extracorporeal membrane oxygenation; 66% of
      doses resulted in up to 100% mean arterial blood pressure increase, and 21% of
      doses resulted in greater than 100% mean arterial blood pressure increase. Doses
      below 1 ug/kg were associated with a lower mean arterial blood pressure increase
      than doses between 1 and 5 ug/kg (mean percent change in mean arterial blood
      pressure = 6.6% vs 60%, respectively). Children less than or equal to 2 years old
      had the greatest percentage increase in heart rate and mean arterial blood
      pressure. CONCLUSIONS: Provision of low-dose bolus epinephrine during periods of
      acute hypotension can result in a significant increase in mean arterial blood
      pressure and heart rate. This dosing strategy may provide temporary stabilization
      while other therapies are added or adjusted, but further research is needed.

PMID- 29319636
TI  - Optimal Antiretroviral Prophylaxis in Infants at High Risk of Acquiring HIV: A
      Systematic Review.
AB  - INTRODUCTION: The risk of perinatal HIV infection can be dramatically reduced
      through maternal antiretroviral (ARV) therapy and infant ARV postnatal
      prophylaxis. The 2013 World Health Organization guidelines recommended 4-6 weeks
      of nevirapine or zidovudine as postnatal prophylaxis, with possible extension to
      12 weeks for high-risk breastfed infants. A systematic review was undertaken to
      determine if there is evidence for the World Health Organization to recommend
      enhanced or extended prophylaxis for high-risk infants. METHODS: Cochrane
      CENTRAL, EMBASE, PubMed databases from 2005 to 2015, as well as conference on
      retroviruses and opportunistic infections and international aids society
      abstracts were searched. Cohort studies and randomized controlled trials
      examining the use of combination or prolonged regimens in HIV-exposed infants
      were included. A total of 1185 studies were screened by title and abstract and 45
      full-text articles were examined in further detail. RESULTS AND DISCUSSION: Of
      the 4 included studies, 3 examined multidrug prophylaxis regimens in formula-fed,
      high-risk HIV-exposed infants. Multidrug regimens were shown to significantly
      reduce transmission rates, compared with single-drug regimens; however, there was
      no significant difference between 2- and 3-drug regimens. An randomized
      controlled trial examining prolonged ARV prophylaxis in a breastfed population
      showed that 6 months of nevirapine resulted in lower HIV transmission rates
      compared with a standard 6-week nevirapine regimen. CONCLUSIONS: The limited
      available evidence suggests that using combination ARV regimens in high-risk
      infants reduces intrapartum transmission and that using prolonged prophylaxis in
      breastfed infants reduces breastfeeding transmission rates. However, the
      additional benefit of combination or prolonged regimens in the context of
      maternal ARV therapy remains unclear.

PMID- 29319637
TI  - Denouement.

PMID- 29319638
TI  - Anomalous Sphenoid Diploe Vein: Case Report Highlighting the Value of Careful CT
      Evaluation Prior to Decompression Surgery.
AB  - Lateral bony decompression may offer several biomechanical advantages and has
      become a commonly used surgical approach. Preoperative imaging plays a key role
      in surgical planning by providing information about the locoregional anatomy. The
      marrow space of the greater wing of the sphenoid is a focal point of the
      decompression surgery based on the volume that it occupies. Several vessels pass
      through the sphenoid bone, but most are small caliber vessels. The authors
      describe a case of an uncommon anatomical variant of the cranial diploic venous
      system in which the anterior transverse diploic vessel traverses the marrow space
      of the sphenoid. The vessel was identified on preoperative CT evaluation. Despite
      anticipation of potential bleeding, lateral decompression was abandoned due to
      difficulties in maintaining hemostasis which compromised the view for safe
      surgical progress.

PMID- 29319639
TI  - Mild Complications or Unusual Persistence of Porcine Collagen and Hyaluronic Acid
      Gel Following Periocular Filler Injections.
AB  - The purpose of this study was to describe the histopathologic appearance of
      dermal eyelid fillers that were unexpectedly encountered in ophthalmic plastic
      surgery samples from patients with mild eyelid disfigurements, and to review
      eyelid cases with complications that had previously been described in the
      literature. A retrospective histopathologic study with Alcian blue, elastic, and
      Masson trichrome stains of 2 cases that were submitted to the Ocular Pathology
      Department was conducted, and a critical review of previously published cases of
      the histopathologic characteristics of dermal filler material in the periocular
      region was also conducted. Two periocular tissue samples were found to contain
      dermal filler material. In one case, porcine collagen appeared as amorphous or
      indistinctly microfibrillar aggregates that stained light blue with the Masson
      trichrome method. In the other case, hyaluronic acid gel appeared as vivid blue
      amorphous pools of material in extracellular locules after staining with the
      Alcian blue method. An inflammatory response was not observed in either case.
      Patients who undergo facial filler procedures may, at a later time, require a
      surgical excisional procedure from which a specimen is generated. Previously
      injected dermal filler that the patient neglected to mention may be present in
      the pathologic sample, potentially perplexing the unsuspecting pathologist. Both
      ophthalmic plastic surgeons and ocular pathologists should be aware of the
      histopathologic features of dermal fillers. It is helpful if a surgeon who
      submits a specimen to the pathology service makes note of any known prior use of
      facial filler material or is alert to its possible presence when unfamiliar
      foreign material is discovered in the dermis of the eyelids.

PMID- 29319640
TI  - Orbital Extranodal Marginal Zone Lymphoma Following Radiotherapy: A Report of 2
      Cases.
AB  - PURPOSE: To present 2 patients in whom orbital radiation preceded the development
      of periorbital extranodal marginal zone lymphoma by more than a decade and to
      investigate the likelihood of this representing irradiation-induced malignancy.
      METHODS: Retrospective chart review and histopathologic study with
      immunohistochemistry of 2 cases. RESULTS: The first patient was a 58-year-old
      woman who developed an orbital mass within the vicinity of the lateral rectus
      muscle 17 years after external beam proton radiation therapy for an
      inferotemporal choroidal melanoma. The second patient was a 32-year-old woman who
      developed a mass in the right lacrimal gland 12 years after external beam photon
      radiation therapy for chronic inflammatory dacryoadenitis. Histopathologic and
      immunohistochemical studies confirmed orbital extranodal marginal zone lymphoma
      in both cases. Retrospective review of older histopathologic slides from the
      second patient revealed underlying immunoglobulin G4-related disease. DISCUSSION:
      The unusual sequence of events in these 2 cases raises the question of whether
      orbital radiation may in rare instances promote the development of orbital
      extranodal marginal zone lymphoma. The literature pertaining to irradiation
      induced secondary malignancy in the orbit is reviewed. CONCLUSIONS: Clinicians
      should consider the possibility of a secondary malignancy when evaluating a
      patient with an orbital mass and a history of prior local radiation exposure.

PMID- 29319641
TI  - Significance of Early Postoperative Eyelid Position on Late Postoperative Result
      in Mueller's Muscle Conjunctival Resection and External Levator Advancement
      Surgery.
AB  - PURPOSE: The purpose of this study was to determine whether advancement of the
      levator aponeurosis in external levator resection surgery or Mueller's muscle and
      conjunctiva in Mueller's muscle conjunctival resection (MMCR) surgery has a
      differential effect on variation in eyelid position during the postoperative
      period. METHODS: In this retrospective observational cohort study, 2 groups of
      patients were defined. The first underwent MMCR surgery without tarsectomy by
      surgeon 1. The second underwent external levator resection without dissection
      posterior to the levator aponeurosis by surgeon 2. Marginal reflex distance
      (MRD1) was calculated based on digital photographs at baseline, 1 week
      postoperatively and at 3-month follow up. The primary outcome measure was change
      in MRD1 over time. The secondary outcome was defined as the proportion of
      patients with minimal early postoperative change (change of MRD1 less than 0.5 mm
      at 1 week postoperatively). Repeated measures analysis of variance, t test, and
      chi-square analyses were performed. RESULTS: Of the 114 eyes in the sample, there
      were 68 in the MMCR group and 46 in the external levator resection group. A
      significant interaction between group and time was noted (p < 0.05), indicating
      change in MRD1 over time was different between the groups. Bonferroni corrected
      multiple comparisons yielded significant differences between each time point for
      MMCR surgery (p < 0.01). No difference in MRD1 was noted for the external levator
      resection group from the early to late postoperative visit. Comparing each time
      point across groups revealed significantly lower MRD1 for the MMCR group at the
      early postoperative visit (p < 0.01). Preoperative and late postoperative MRD1
      did not significantly differ between the groups. Regarding the secondary outcome,
      patients undergoing MMCR surgery were 3.7* as likely to demonstrate <0.5 mm of
      change in MRD1 at week 1 (p < 0.05). When considering the 39.7% (n = 27) MMCR
      patients in this category, 59.3% (n = 16) went on to show an MRD1 increase >1 mm
      from the early postoperative to the late postoperative time points. CONCLUSIONS:
      Both external levator resection and MMCR can effectively elevate the eyelid in
      cases of primary involutional ptosis, and have similar late postoperative
      results. The authors found that MMCR cases undergo greater change between the
      early and late postoperative period, suggesting the process of eyelid elevation
      after MMCR may be dynamic, involving postoperative physiologic modification.

PMID- 29319642
TI  - Ring in the New Year With Exciting STN Projects.

PMID- 29319643
TI  - Burnout, Perceived Stress, and Job Satisfaction Among Trauma Nurses at a Level I
      Safety-Net Trauma Center.
AB  - Nurses are at the forefront of our health care delivery system and have been
      reported to exhibit a high level of burnout. Burnout and stress in trauma nurses
      at a safety-net hospital can negatively impact patient care. Safety-net hospitals
      are confronted with unique social, financial, as well as resource problems that
      can potentially make the work environment frustrating. The purpose of this study
      was to explore the levels of burnout, stress, and job satisfaction in nurses
      providing care to trauma patients at a Level I safety-net trauma center. A cross
      sectional survey design was used to investigate principal factors including
      personal and professional demographics, burnout, perceived stress, and job
      satisfaction. Trauma nurses working at a Level I safety-net trauma center are
      stressed and exhibited moderate degree of burnout. The extent of emotional
      exhaustion experienced by the nurses varied with work location and was highest in
      surgical intensive care unit nurses. The level of job satisfaction in terms of
      opportunities for promotion differed significantly by race and the health status
      of the nurses. Satisfaction with coworkers was lowest in those nurses between the
      ages of 60-69 years. Female nurses were more satisfied with their coworkers than
      male nurses. In addition, the study revealed that significant relationships exist
      among perceived stress, burnout, and job satisfaction. Work environment
      significantly impacts burnout, job satisfaction, and perceived stress experienced
      by trauma nurses in a safety-net hospital. Nursing administration can make an
      effort to understand the levels of burnout and strategically improve work
      environment for trauma nurses in order to minimize stressors leading to attrition
      and enhance job satisfaction.

PMID- 29319644
TI  - Improving Thermoregulation for Trauma Patients in the Emergency Department: An
      Evidence-Based Practice Project.
AB  - Extensive evidence exists on the association between hypothermia and increased
      morbidity and mortality in trauma patients. Gaps in practice related to
      temperature assessment have been identified in literature, along with limited
      personnel knowledge regarding management of patients with accidental hypothermia.
      An interdisciplinary team identified gaps in practice in our institution
      regarding temperature assessment and documentation of rewarming and initiated an
      evidence-based practice project to change practice at our institution. The goals
      were to decrease time to temperature assessment, increase core temperature
      assessment, and increase implementation of appropriate rewarming methods. This
      project used the Iowa Model of Evidence-Based Practice to provide a framework for
      execution and evaluation. We conducted a literature review to address all aspects
      of hypothermia, including incidence, associated and contributing factors,
      prevention, recognition, and treatment. This evidence-based knowledge was then
      applied to clinical practice through staff education and training, equipment
      availability, and environmental adjustments. More patients with hypothermia and
      hyperthermia were identified in 2017, as compared with 2016. There was a
      significant increase in core temperature assessment from 4% in 2016 to 23% in
      2017 (p < .001). Blanket use in normothermic patients increased in 2017 (p =
      .002). This project is an example of how nurses can utilize an evidence-based
      practice model to translate research into clinical practice. Best practice
      interventions regarding temperature assessment and rewarming measures for trauma
      patients can be successfully implemented with negligible cost. Further research
      should be dedicated to examine barriers to implementation and adherence to
      evidence-based practice interventions.

PMID- 29319645
TI  - Improving Thermoregulation for Trauma Patients in the Emergency Department: An
      Evidence-Based Practice Project.

PMID- 29319646
TI  - Effect of Telenursing on Outcomes of Provided Care by Caregivers of Patients With
      Head Trauma After Discharge.
AB  - Telenursing is a suitable tool for increasing health-related awareness of the
      caregivers for a better home care. But its efficacy may be affected by several
      factors. Considering the important complications of head trauma injury and high
      rate of readmission, we aimed to assess the effect of telenursing on care
      provided by the family members of patients with head trauma.This randomized
      controlled trial investigated 72 patients with head trauma, who were randomly
      allocated to intervention and control groups (36 patients in each group). The
      caregivers in both groups were provided with 1-hr face-to-face training session
      on patients' home care and educational booklets. The patients in the intervention
      group were followed up every week through phone calls by the telenurse for 12
      weeks, who recorded the patient's status, as well. Caregivers in the intervention
      group could call the telenurse any time they desired. The health status of the
      control group was followed once by a phone call after 12 weeks. Data on patients'
      readmission and pressure ulcer (based on Norton's scale) rate and time were
      compared between the groups and analyzed using SPSS software, version 19. Thirty
      three patients with a mean +/- SD age of 31.12 +/- 10.83 years were studied in
      the control group and 35 patients with a mean +/- SD age of 34.11 +/- 12.34 years
      in the intervention group (p = .098). None of the patients in the intervention
      group were readmitted, whereas 2 patients in the control group were readmitted
      s(p = .139). Risk of pressure ulcer did not differ between the groups (p = .583).
      Telenursing had no significant effect in readmission and decubitus prevention for
      patients with head trauma. Considering the chronic nature of the illness, a
      longer follow-up period is deemed necessary for an accurate conclusion.

PMID- 29319647
TI  - Transition to Critical Care Practice Within an Academic-Service Partnership: A
      Case Report of the First 3 Years of Clinical Immersion in Trauma-Burn and
      Neuroscience Critical Care.
AB  - In response to regulators of nursing education and the Institute of Medicine, an
      academic-service partnership was formed between a research-intensive school of
      nursing and a tertiary health care facility. In that partnership, clinical
      experiences occurred mostly within 1 organization. This case report showcases the
      development, implementation, and revisions within our capstone immersion course,
      designed to ease the new graduates' transition into practice, including
      transitions to critical care nursing. Herein, we highlight our successes and
      challenges of implementing the clinical component within 2 critical care units
      focused on trauma and neurosurgical care of complex patients. Its purpose is to
      describe the planning and orientation phase, illustrate the mentoring processes
      used to achieve the educational outcomes, and describe the benefits and
      challenges of such an immersion experience. Our redesigned clinical immersion
      course in high-acuity nursing is facilitated by our partnership and resulted in
      improved RN-NCLEX rates, facilitation of best practices, and ease of transition
      into novice graduate nurse roles.

PMID- 29319648
TI  - Resuscitative Endovascular Balloon Occlusion of the Aorta for Hemorrhage Control
      in Trauma Patients: An Evidence-Based Review.
AB  - Traditionally, resuscitative efforts for uncontrolled noncompressible torso
      hemorrhage are achieved by cross-clamping the proximal aorta via thoracotomy to
      deliver temporary hemodynamic stability during injury repair. A less commonly
      used method of promoting early resuscitation and hemorrhagic control in trauma
      patients is resuscitative endovascular balloon occlusion of the aorta (REBOA).
      The focus of this literature review is to examine the effectiveness of REBOA in
      the management of noncompressible pelvic hemorrhage when compared with
      traditional methods of hemorrhage control in trauma patients. A literature search
      was performed by using the PubMed database to explore studies that defined the
      efficacy of REBOA or compared the use of REBOA with resuscitative thoracotomy
      with aortic cross-clamping for hemorrhage control. Studies encompassed in the
      review included 3 experimental studies utilizing swine, 2 retrospective studies
      that reviewed data collected from procedures performed in empirical situations,
      and a case series that described the implementation of REBOA. Trauma patients
      with noncompressible torso hemorrhage that is intervened with REBOA have higher
      mean arterial pressures and systolic blood pressures, require fewer boluses of
      intravenous fluids and vasopressors, avoid severe acidosis and ischemia, and have
      significantly lower rates of mortality, thus ensuring enhanced long-term
      outcomes. Evidence suggests that hemodynamic stability, physiological effects,
      and mortality rates are improved in patients who receive REBOA for torso
      hemorrhage control when compared with traditional methods.

PMID- 29319650
TI  - Decreasing Radiation Exposure in Pediatric Trauma Related to Cervical Spine
      Clearance: A Quality Improvement Project.

PMID- 29319649
TI  - Decreasing Radiation Exposure in Pediatric Trauma Related to Cervical Spine
      Clearance: A Quality Improvement Project.
AB  - STUDY DESIGN: Quality improvement project. OBJECTIVES: Reduce the amount of
      radiation exposure in the pediatric trauma population 5 years of age and older in
      relation to cervical spine clearance. BACKGROUND: The evaluation of pediatric
      cervical spine injuries must be accurate and timely to avoid missed injuries. The
      difficult clinical examination in pediatric trauma patients necessitates the use
      of radiologic examinations to avoid missing catastrophic injuries. However,
      exposure to radiation at an early age increases the pediatric patients' risk of
      developing cancer (R. A. ). METHODS: A retrospective chart review was conducted
      to assess radiation exposure in pediatric patients requiring evaluation for
      cervical spine clearance. Surgical staff and emergency department physicians
      received education on the risks related to pediatric radiation exposure and
      information related to the institution's diagnostic trends for cervical spine
      clearance. An algorithm was then developed to assist with determining the
      necessary imaging study for cervical spine clearance. Radiation exposure was
      monitored following initial education and use of the algorithm to determine its
      effect on radiation exposure. RESULTS: The retrospective chart review identified
      cervical spine computed tomography (CT) in 34%, with an average radiation
      exposure of 3.5 mSv. Following education and introduction of an algorithm, 18% of
      patients underwent CT for cervical spine clearance with an average radiation
      exposure of 3.2 mSv, representing a 47% decrease in the use of CT. CONCLUSION:
      Staff education and the use of an algorithm show promise in the reduction of
      radiation exposure and provide safe, effective clearance of the cervical spine in
      pediatric trauma.

PMID- 29319651
TI  - Proper Education on Spinal Orthotics: A Way to Minimize Associated Complications.
AB  - Spinal orthotic bracing is a common modality for treating nonoperative spinal
      fractures with risks. This study aimed to assess the effect of an intervention on
      critical care nurses to improve their clinical knowledge and comfort level of
      managing patients. A literature review was conducted regarding common
      complications associated with spinal orthotics. This information was compiled and
      used to create a questionnaire and spinal orthotic course for nurses. Pre- and
      postassessments of nurses' knowledge regarding spinal orthotics were conducted. A
      total of 197 nurses completed the presentation. The ability to correctly identify
      thoracolumbosacral orthotics (TLSO), lumbosacral orthotics (LSO) and cervico
      thoracic orthotics (CTO) all significantly increased. Regarding the clinical
      knowledge, the right answer to the question whether or not halo vest needed to be
      removed for cardiopulmonary resuscitation increased from 45.2% to 100% (p <
      .0001), and the correct answer to the question whether or not TLSO braces need to
      be worn at all times in patients with spinal precautions increased from 62.4% to
      100% (p < .0001). Nurses reported that their comfort level of taking care of
      patients with spinal precautions increased from 94.4% before the presentation to
      100% after the presentation. The quality improvement project seemed to improve
      the critical care nurses' ability to correctly identify different type of braces
      and their comfort level of managing patients with spinal precautions.

PMID- 29319652
TI  - Pain Assessment in Mechanically Ventilated, Noncommunicative Severe Trauma
      Patients.
AB  - The aim of this study was to measure pain levels in noncommunicative patients
      with severe trauma who required tracheal suctioning and mobilization and to
      determine the utility of the Behavioral Indicators of Pain Scale (ESCID) in these
      cases. The pain scores for the procedures were recorded on Days 1, 3, and 6 of
      the patients' stay in the intensive care unit. These assessments were performed
      at 3 moments: before, during, and after the application of the procedures.
      Because of the longitudinal character of the study, data were fitted into a
      multivariate model using the Generalized Estimating Equations method. The sample
      of 124 patients comprised 77.4% males and 22.6% females with an average age of
      45.93 (SD = 16.43) years. A significant increase (p < .01) in the ESCID score was
      observed during the application of the procedures that produced similar pain
      levels. Kappa coefficient value obtained for interobserver agreement of ESCID
      scale scores during the application of care procedures at the intervals being
      evaluated was greater than 0.84, which should be interpreted as almost perfect.
      The ESCID scores increased during 2 care procedures that are frequently carried
      out in intensive care units and indicated that they produced similar pain levels.

PMID- 29319653
TI  - Posttraumatic Stress Syndrome: What Is It?
AB  - Readily defined as symptoms consistent with posttraumatic stress disorder (PTSD),
      but that occur earlier than 30 days after experiencing the traumatic event,
      posttraumatic stress syndrome (PTSS) is now acknowledged to be a serious health
      issue. Even so, PTSS often goes unrecognized until an official diagnosis of PTSD
      is made. Screening tools such as the PTSS-14 have proven reliable in identifying
      people with PTSS who are at risk of developing PTSD. Through early recognition,
      providers may be able to intervene, thus alleviating or reducing the effects of a
      traumatic experience.

PMID- 29319654
TI  - Trauma and Intensive Care Nursing Knowledge and Attitude of Foley Catheter
      Insertion and Maintenance.
AB  - In the acute care setting, the majority of urinary tract infections are
      associated with indwelling urinary catheters. Despite guidelines for proper use,
      catheter-associated urinary tract infections (CAUTIs) continue to occur in
      critically ill/injured patients. There is a paucity of data on the translation
      between CAUTI prevention education and behavioral change. This project evaluated
      nurse's clinical knowledge and attitude toward Foley catheter insertion and
      maintenance to determine the benefits of addressing gaps in knowledge and
      inconsistencies in attitude through education.A prospective cohort study was
      conducted with registered nurses from the emergency room, trauma/surgical, and
      medical intensive care units. Participant's clinical knowledge and attitude
      toward Foley catheter usage and CAUTIs were evaluated using a 20-question survey
      tool before and after a CAUTI education program.Forty-eight nurses completed the
      presurvey, educational training, and postsurvey. The mean postsurvey score was
      significantly higher (86.9 +/- 8.3%) than the presurvey score (76.0 +/- 12.3%)
      for the knowledge section of the survey. There was no marked difference in
      participant attitude following the educational training, with mean presurvey and
      postsurvey scores of 91.3 +/- 7.0% and 89.8 +/- 5.3%, respectively. After the
      course, participants were more confident in their clinical knowledge; however,
      perception regarding CAUTI prevention did not improve. A series of unannounced
      rounding observations before and after the intervention showed an improvement in
      proper Foley catheter maintenance.Catheter-associated urinary tract infection
      prevention education was an effective countermeasure to address gaps in clinical
      knowledge, but modifying attitudes was difficult to achieve. In the short term,
      the training appeared to improve proper maintenance in clinical practice.

PMID- 29319655
TI  - Superior Capsular Reconstruction with a Partial Rotator Cuff Repair: A Case
      Report.
AB  - CASE: Chronic massive irreparable rotator cuff tears remain challenging to treat.
      We present the case of a 70-year-old active and healthy woman who presented with
      6 months of worsening shoulder pain and function; she had experienced
      considerable deterioration over the past 2 months. Nonoperative management of the
      massive rotator cuff tear was not successful. Superior capsule reconstruction
      (SCR) was performed with a partial rotator cuff repair. CONCLUSION: SCR is an
      exciting advancement for the chronic massive irreparable rotator cuff tear, one
      of the more challenging problems encountered by shoulder surgeons. Our patient
      was doing well at the 1-year follow-up and was very satisfied with the outcome.

PMID- 29319656
TI  - Isolated Rhabdomyolysis of the Infraspinatus Muscle Following the CrossFit "Sissy
      Test": A Report of Two Cases.
AB  - CASE: Following the completion of a CrossFit-style challenge (the "Sissy Test"),
      2 patients presented with severe pain and swelling over the posterior aspect of
      the scapula. Magnetic resonance imaging demonstrated isolated edema of the
      infraspinatus muscle in both patients; the compartments were compressible.
      Neurovascular checks and observation of range of motion were performed. The
      patients were treated nonoperatively and were discharged with the diagnosis of
      overuse syndrome with rhabdomyolysis of the infraspinatus muscle. CONCLUSION:
      With marked increase in the popularity of extreme fitness, monitoring for
      rhabdomyolysis and potential renal dysfunction is essential.

PMID- 29319657
TI  - Sciatic Nerve Entanglement Around a Femoral Prosthesis During Closed Reduction of
      a Dislocated Total Hip Prosthesis: The Role of Metal-Suppression MRI: A Case
      Report.
AB  - CASE: A 68-year-old woman who had undergone a right total hip arthroplasty
      presented with a right posterior hip dislocation, and subsequently developed an
      ipsilateral sciatic nerve palsy after closed reduction. Magnetic resonance
      imaging (MRI) with metal suppression demonstrated sciatic nerve entanglement
      around the prosthetic femoral neck. A sciatic nerve release was performed,
      resulting in poor early neurologic recovery. CONCLUSION: Sciatic nerve
      entanglement following closed reduction of a dislocated total hip prosthesis is a
      rare injury. Assessment of neurovascular status before and after reduction is
      imperative. We recommend prompt MRI with metal suppression in patients with acute
      neurologic symptoms following reduction of a dislocated hip prosthesis to
      evaluate for acute nerve pathology and assess the need for emergency surgery.

PMID- 29319658
TI  - Reply.

PMID- 29319659
TI  - Residual Neurological Symptoms After Peripheral Nerve Blocks for Pediatric Knee
      Surgery.
AB  - BACKGROUND: Peripheral nerve blocks (PNBs) provide excellent pain control and
      reduce the need for systemic analgesics in orthopaedic surgery. PNBs rarely cause
      complications; however, a few studies of adults have reported neurological
      complications during the early postoperative period. We investigated
      complications associated with the use of PNBs during pediatric knee surgery.
      METHODS: We reviewed the medical records of all 121 children (aged <=18 y) who
      underwent knee surgery by 1 orthopaedic surgeon between October 2014 and
      September 2016. One hundred of these patients had PNBs. The primary outcome of
      interest was postoperative neurological symptoms. Other study parameters were
      patient characteristics, surgical details, tourniquet use/duration of use, PNB
      guidance method and anatomic location, and PNB-associated procedural
      complications (eg, blood loss, anesthetic neurotoxicity). Data were analyzed
      using Student t tests and Fisher exact tests, with significance at P<0.05.
      RESULTS: Of the 100 patients with PNBs, 23 had persistent lower-extremity
      paresthesias postoperatively. Most paresthesias were attributed to the surgical
      procedure; however, at first follow-up (mean, 1.6+/-0.4 wk) 6 patients had
      paresthesias and other neurological symptoms proximal to the knee in a
      distribution pattern consistent with the PNB. Three of these were unresolved at
      last follow-up (mean, 56+/-37 wk). All neurological symptoms were associated with
      femoral nerve blocks. The 6 patients with suspected PNB-associated neurological
      symptoms had a significantly higher mean BMI (31+/-5.5) than the 94 patients
      without symptoms (23+/-6.1; P=0.002). Obesity was associated with PNB-associated
      neurological symptoms (P=0.002), as was female sex (P<0.001). No significant
      differences were found in terms of age, surgery duration, or tourniquet
      use/duration of use. Most PNB procedures used ultrasound guidance, and no
      procedural complications were reported. CONCLUSIONS: Compared with previous
      studies, we report a higher rate (6%) of PNB-associated neurological symptoms in
      children after knee surgery with PNBs. Obesity and female sex were associated
      with persistent neurological symptoms in the distribution pattern of the PNB.
      LEVEL OF EVIDENCE: Level III (retrospective comparative study).

PMID- 29319660
TI  - Obesity's Influence on Operative Management of Pediatric Supracondylar Humerus
      Fractures.
AB  - BACKGROUND: As childhood obesity remains an ongoing issue for the United States
      there has been an increasing number of studies detailing its effect on fracture
      complexity, management, and outcomes. This study utilizes a national database to
      examine whether obese children with supracondylar humerus fractures are more
      likely to require open reduction and internal fixation than nonobese children.
      METHODS: The Healthcare Cost and Utilization Project Kid's Inpatient Database of
      2003, 2006, 2009, 2012 were queried for pediatric supracondylar humerus fractures
      [International Classification of Disease (ICD-9), 812.41] between 2 and 12 years.
      Patients were separated into those undergoing closed reduction percutaneous
      pinning (CRPP), open reduction internal fixation (ORIF), or both. Obesity was
      determined by comorbidity and ICD-9 coding (ICD-9, 278.00, 278.01). Univariable
      and multivariable logistic regression models were utilized with P<0.05 considered
      significant. RESULTS: Between 2003 and 2012, 31,905 patients between the ages of
      2 and 12 years sustained supracondylar humerus fractures. In total, 105 patients
      (0.3%) were obese. A majority of patients, 27,658 (86.7%), underwent CRPP. Odds
      for ORIF increased in association with age, obesity, white race, and private
      insurance. Significant association was found between age and obesity (P<0.05) in
      those undergoing ORIF. Obese children between 2 and 7 years of age had no
      difference in ORIF or CRPP compared with normal-weight children. Those between 8
      and 12 years who were obese were significantly more likely to undergo ORIF (OR,
      4.29; 95% confidence interval, 1.78-10.36). CONCLUSIONS: Supracondylar humerus
      fractures sustained in obese children between 8 and 12 years are over 4 times
      more likely to require ORIF compared with normal-weight children of the same age.
      Providers should identify and counsel older obese children and their families
      regarding the potential for increased difficulty in fracture management that may
      require open surgical intervention. LEVEL OF EVIDENCE: Level IV-case series.

PMID- 29319661
TI  - Observed Length Increases of Magnetically Controlled Growing Rods are Lower Than
      Programmed.
AB  - BACKGROUND: Magnetically controlled growing rods (MCGRs) are increasingly used in
      the treatment of early onset scoliosis (EOS). Few studies have reported whether
      desired lengthening can reliably be achieved, or if prior spine instrumentation
      and large tissue depths affect lengthening. In this clinical study of EOS
      patients, it was hypothesized that increases in rod length would equal programmed
      increases, patients with prior spine instrumentation would lengthen less than
      patients without prior surgery, and larger tissue depths would decrease
      lengthening success. METHODS: A retrospective chart review was conducted on EOS
      patients with single and dual MCGRs placed between April 2014 to September 2015
      and distracted at a single institution. Rod distraction was measured at each
      visit using ultrasound. Differences between programmed and actual distraction for
      each patient, and between groups with and without prior spine instrumentation,
      were determined by 2-tailed t tests. Regression and correlation were used to
      determine the relationship between tissue depth and length increases. RESULTS:
      Thirty-one patients were included, 18 males, 13 females, age 8.1 (+/-2.5) years,
      with major curves measuring 60 (+/-14.6) degrees at time of MCGR insertion. In
      the 12 patients with prior instrumentation, time from initial growing rod
      placement to MCGR insertion was 23.1 (+/-10.6) months. The number of surgical
      procedures before MCGR insertion was 2.8 (+/-2.0). Total length increase relative
      to the programmed distraction was 86% (+/-21) (P<0.001). Length increases for
      patients with and without prior surgery were 87% (+/-23) and 86% (+/-19),
      respectively (P>0.9). Total lengthening was inversely proportional to tissue
      depth (r=0.38, P<0.01); the decrease in lengthening achieved was 2.1%/mm of
      tissue depth. CONCLUSIONS: Increases in rod length were 14% lower than the
      programmed distraction. Prior instrumentation did not impact the amount of rod
      distraction. Greater distance between the rod and the skin surface negatively
      affected the magnitude of distraction.

PMID- 29319662
TI  - Historical Analysis of Bibliometric Trends in the Journal of Pediatric
      Orthopaedics With a Particular Focus on Sex.
AB  - BACKGROUND: Orthopaedics is the clinical discipline with the lowest percentage of
      female residents and faculty. Pediatric orthopaedics has a higher percentage of
      women than other orthopaedic subspecialties. It was the purpose of this study to
      examine bibliometric trends in the Journal of Pediatric Orthopaedics (JPO) with a
      specific focus on sex. METHODS: A bibliometeric analysis for the years 2015,
      2005, 1995, 1985, 1981 was performed. The names of first and corresponding
      authors; corresponding author position; country of origin; number of
      institutions, countries, authors, printed pages, and references was tabulated.
      Author sex was identified for the first and corresponding authors using the "Baby
      Name Guesser" (www.gpeters.com/names/baby-names.php). A P<0.05 was considered
      significant. RESULTS: There were 746 publications; 68.7% were from North America.
      The average number of authors, corresponding author position, collaborating
      institutions, countries, and number of references increased, whereas the number
      of printed pages decreased. Asia had the greatest number of authors (4.4), with
      Australia/New Zealand the fewest (3.4). Sex was determined for 98.3% of the first
      authors and 98.5% of the corresponding authors. There was a significant increase
      in the number of female first authors over time (5.9% to 25.6%, P<10), especially
      in Europe and North America. There were significant increase in the number of
      female corresponding authors over time (5.8% to 17.6%, P=0.000009). There was a
      significant trend to have a greater percentage of both female first and
      corresponding authors over time (P=0.0005) with a reverse trend for both male
      first and corresponding authors (P<10). CONCLUSIONS: In this study, we noted that
      the number of female first and corresponding authors in Journal of Pediatric
      Orthopaedics has been steadily increasing. This should result in more female
      pediatric orthopaedic surgeons in academic faculty positions.

PMID- 29319663
TI  - [Regional ophthalmological cluster as a resource basis for the process and the
      procedure of specialist accreditation].
AB  - : Since 2016, phased introduction of specialist accreditation has been launched.
      Many issues like how training at regional accreditation centers (RACs) should be
      organized - for applicants applying for primary specialized accreditation as
      residents in ophthalmology (2018) or periodic accreditation as practicing
      ophthalmologists (2021) - are yet debatable. AIM: to provide organizational and
      educational resources for arranging accreditation of ophthalmologists at the
      background of improving the quality of medical care in a federal subject of the
      Russian Federation. MATERIAL AND METHODS: The study object was the process and
      the procedure of accreditation, the study subject - the system of specialist
      accreditation. METHODS: bibliographical, analytical, and expert. Methodological
      basis for tasks solving: mobilization of an independent organizational structure,
      that is, the regional ophthalmological scientific-educational cluster (ROSEC).
      RESULTS: Three complex problems have been defined that require solution. 1.
      Discrepancies between accreditation procedures depending on the type of
      accreditation. The absence of practical skills assessment within the periodical
      accreditation procedure and low availability of innovative simulation systems
      impede the achievement of the declared goals of accreditation. 2. The absence of
      a clear order and criteria for portfolio assessment as well as a legal format of
      its formation during non-interrupted medical education (NIME) demands active
      management. 3. There is still a lack of appropriate organizational, educational,
      material technical, and personnel support of the accreditation system. The
      proposed organizational and methodological approaches are aimed at solving issues
      of accreditation support, proper functioning of RACs, and improving the quality
      and regional availability of NIME. CONCLUSION: Systematic approach effectively
      solves the problem of resource support of accreditation. ROSEC should be regarded
      as the provision basis for complex of all stages of ophthalmologist accreditation
      and proper functioning of RACs. ROSEC involvement is highly advisable.

PMID- 29319664
TI  - [Differential diagnostic OCT-criteria of acute and chronic central serous
      chorioretinopathy].
AB  - : Principal differences in natural history, therapeutic approaches, and
      functional prognosis of acute and chronic central serous chorioretinopathy (CSC)
      requires that they were distinguished. AIM: to define differential diagnostic
      criteria for acute and chronic CSC basing on the chorioretinal complex analysis
      by EDI-optical coherence tomography (OCT). MATERIAL AND METHODS: A retrospective
      analysis was performed that included data of 112 patients with CSC, who were
      assigned to either the 'acute' (52 patients) or 'chronic' (60 patients) group
      depending on symptoms duration (3 months) and fluorescein angiography findings.
      With the enhanced depth imaging (EDI) module mounted on OCT (Spectralis,
      Heidelberg, Germany), the structure of the chorioretinal complex was studied.
      RESULTS: In acute CSC, the height of the neuroepithelium detachment (310.73+/
      113.63 MUm) was greater than that in chronic CSC (205.68+/-90.80 MUm), p=0.03.
      The frequency of subretinal deposits also differed (17.3% and 100% of cases,
      respectively), p<0.01. The subfoveal choroidal thicknesses were similar (462.7+/
      110.7 and 494.7+/-132.1 MUm, respectively, p=0.6), however, in acute CSC, diffuse
      thickening of the choroid was noted (39 patients, 75% of cases), while chronic
      CSC was marked by local dilatation of the Haller's layer (39 eyes, 65% of cases).
      The diameter of hyporeflective pockets in the Haller's layer in the 'acute'
      (324+/-98.1 MUm) and 'chronic' (352.0+/-84.3 MUm) groups correlated with
      choroidal thicknesses (r=0.68, r=0.75). Hyperreflective intrachoriodal dots were
      more common in the 'chronic' group (acute - 1.9%, chronic - 68.3%), so did
      hyperreflective vascular walls -13.5% and 68.3%, respectively, p<0.01. Dome
      shaped RPE detachments were observed equally often in both groups (acute - 67.3%,
      chronic - 68.3%, p=0.9), while the 'double-layer sign' was only characteristic of
      chronic CSC (86.7%). CONCLUSION: OCT criteria of acute CSC include a dome-shaped
      detachment of neuroepithelium and diffuse thickening of the choroid in the
      absence of deposits; of chronic CSC - subretinal deposits, local dilatation of
      the Haller's layer vessels, hyperreflective vascular walls, intrachoroidal dots,
      and the 'double-layer sign'.

PMID- 29319665
TI  - [Clinical and functional results of one-step phaco surgery and central
      descemetorhexis for cataract and Fuchs primary endothelial corneal dystrophy].
AB  - : Poor visual function associated with Fuchs endothelial corneal dystrophy (FECD)
      is one of the main indications for keratoplasty. Reports of successful visual
      rehabilitation of patients with spontaneous or scheduled removal of the
      Descemet's membrane and the endothelium or donor material adhesion failure,
      suggest this research direction perspective. AIM: to evaluate the potential as
      well as clinical and functional outcomes of phacoemulsification with central
      circular descemetorhexis in patients with Fuchs endothelial corneal dystrophy.
      MATERIAL AND METHODS: A total of 19 patients aged 51-84 years were included. The
      preoperative best corrected visual acuity averaged 0.32+/-0.19, endothelial cells
      density - 629.6+/-336.9 cells/mm2, and central corneal pachymetry - 587.8+/-44.8
      um. After phacoemulsification with IOL implantation, a 4 mm tap was created from
      the epithelial side of the cornea. Central circular descemetorhexis was done
      using a microhook. The membrane was removed with microforceps. RESULTS: On day 1,
      there was central corneal edema matching the circular defect in the Descemet's
      membrane. As many as 26.3% of patients demonstrated rapid responses to the
      treatment, which implies that corneal transparency and visual improvement were
      achieved by the end of the first month after surgery. In other 26.3% of patients,
      full corneal transparency was not achieved and, therefore, endothelium
      transplantation had to be performed. The main group included 12 patients. At 12
      months, the best corrected visual acuity was 0.66+/-0.29, central pachymetry -
      569.27+/-63.74 um, endothelial cells density - 634.00+/-170.41 cells/mm2.
      CONCLUSION: In 63.8% of patients, visual rehabilitation was achieved without
      endothelial transplantation, which provides new prospects for tissue-saving
      technologies in patients with endothelial corneal dystrophy.

PMID- 29319666
TI  - [Visual rehabilitation of patients with large post-traumatic defects of the
      anterior eye segment through iris-lens diaphragm implantation].
AB  - : The diversity of methodological approaches and lack of pathogenetically
      reasonable tactics for patients with combined ocular injuries became the basis
      for the development and systematization of surgical rehabilitation stages of
      patients, in whom post-traumatic cataract is combined with post-traumatic
      aniridia and corneal scarring. AIM: to construct a visual rehabilitation approach
      to patients with post-traumatic defects of the anterior eye segment following
      optical-reconstructive surgery that involved implantation of an iris-lens
      diaphragm (ILD). MATERIAL AND METHODS: We have analyzed 80 reconstructive cases
      with ILD implantation in patients with post-traumatic aniridia and corneal
      damage. These patients constituted the first study group (Group 1). We have also
      investigated 58 eyes with residual ametropy and stable visual function 1 year
      after ILD implantation before and after conducting a laser keratorefractive
      surgery. These patients were assigned to the second study group (Group 2).
      RESULTS: Rehabilitation approach to patients after anterior segment injuries that
      has been proposed allows to achieve high clinical and functional results and
      reduce the risk of intra- and postoperative complications. CONCLUSION: The
      proposed approach to patients after optical-reconstructive surgery with iris-lens
      diaphragm implantation followed by keratorefractive surgery is an effective
      method of visual rehabilitation of anterior eye segment post-traumatic defects.

PMID- 29319667
TI  - [Diagnostic capabilities of optical coherence tomography and confocal laser
      scanning microscopy in studying manifestations of aniridia-associated
      keratopathy].
AB  - AIM: to investigate the possible use of anterior segment optical coherence
      tomography (AS-OCT) and laser scanning confocal microscopy (LSCM) for
      visualization of limbal progenitor structures and epithelial changes at different
      stages of aniridia-associated keratopathy (AAK) and to analyze genotype-phenotype
      correlations of corneal damage. MATERIAL AND METHODS: Thirty-four patients (63
      eyes) with congenital aniridia (CA) were subjected to epithelial cell density
      measurement in the central cornea as well as epithelial surface assessment with
      limbal palisades of Vogt (POV) detection in the corresponding sites of the two
      corneas. For that, LSCM (HRT3) and AS-OCT (RTVue XR Avanti) were performed.
      Central corneal and epithelial thicknesses were measured using the Pachymetry
      protocol. RESULTS: There has been found an increase in the central corneal
      thickness (CCT) of CA patients, which correlated with the stage of AAK, and a
      decrease in the central epithelial thickness as compared with healthy subjects
      (p<0.05). The difference between the basal and wing epithelial cells density in
      eyes with stages I and II AAK and normal cells density at stage 0 AAK was
      statistically significant (p<0.05). Intact or disturbed POV were detected in all
      patients with PAX6 3' deletion. At that, AS-OCT findings highly agreed with LSCM
      images for both the inferii (rS=0.85, p<0.05) and superior limbi (rS=0.53,
      p<0.05). A negative correlation was established between the stage of AAK and in
      vivo morphology of POV (rS=-0.5, p<0.05). However, no correlation was found
      between the stage of AAK and patient's age (rS=0.169, p=0.174). CONCLUSION: AS
      OCT and LSCM are both important diagnostic tools for corneal surface monitoring
      in patients with limbal stem cells deficiency.

PMID- 29319668
TI  - [Combined YAG-laser capsulotomy in pseudophakic patients with anterior capsular
      contraction syndrome].
AB  - : Progressive metaplastic fibrosis of the anterior capsulorhexis opening is a
      frequent complication of the postoperative period. There is a widely practiced
      method of anterior capsular contraction syndrome (ACCS) correction through radial
      anterior laser capsulotomy. Despite many advantages, it can be complicated by
      unpredictable anterior capsule tearing and intraocular lens (IOL) dislocation
      into the vitreous Body, which justifies the search for new technical solutions.
      AIM: to develop a safe technique of combined laser anterior capsulotomy (LAC) in
      patients with ACCS. MATERIAL AND METHODS: The study included 19 patients (20
      eyes) with ACCS. The suggested LAC technique involved two differently directed
      YAG-laser cuts that could be regarded as a combination of radial anterior
      capsulotomy and anterior peripheral linear capsulotomy. With the cuts located
      perpendicularly to each other, the distal end of each radial cut was connected to
      the middle of each longitudinal cut. RESULTS: The suggested technique allows an
      increase in the anterior capsulorhexis diameter up to more than twice the pre
      laser size. The difference between the average pre- and post-laser capsulorhexis
      diameters was statistically significant (r<0.0001). Neither case developed an
      unpredictable anterior capsule tear. CONCLUSION: The safety of the new technique
      is ensured by preliminary longitudinal cuts that create a barrier against
      unpredictable radial tears in the capsular bag during radial capsulotomy.

PMID- 29319669
TI  - [Analysis of structure, causes, and risk factors of ischemic optic neuro-pathy].
AB  - AIM: to analyze the structure, risk factors, and causes of ischemic optic
      neuropathy (ION). MATERIAL AND METHODS: A total of 239 patients (303 eyes) with
      ION and 98 patients (185 eyes) with optic disc drusen were examined. All ION
      patients underwent general clinical assessment. Those under 50 years of age were
      also tested for antiphospholipid markers and gene polymorphisms of the
      coagulation system. RESULTS: All patients were found to be exposed to two or more
      modifiable risk factors of ION. A total of 47.1% of cases were judged as being at
      anatomical risk of anterior ION (AION) with the cup-to-disc ratio in the second
      eye of less than 0.15 (of less than 0.25 in 53% of cases). Of 98 patients (185
      eyes) with optic disc drusen, 5.4% of cases (10 eyes) developed AION. As many as
      22% of ION patients were under 50 years of age. Of them, in 32% primary APS was
      diagnosed, in 3.6% - secondary (in the presence of SLE); all cases were positive
      for polymorphisms of the coagulation system that determine genetic predisposition
      to ION (indeed, the frequency of the latter was significantly higher in these
      patients than in the control group). CONCLUSION: Ischemic optic neuropathy is an
      optic nerve disorder that requires thorough medical history taking and
      comprehensive assessment of the patient in order to identify the causes and risk
      factors of this disease as well as accompanying pathologies.

PMID- 29319670
TI  - [Dynamics of electrophysiological parameters of the retina after surgical
      treatment of idiopathic macular hole].
AB  - AIM: to study the dynamics of recovery of electrophysiological parameters of the
      retina after surgical treatment of idiopathic macular hole (IMH) and to assess
      their relevance to functional prognosis of the operation. MATERIAL AND METHODS:
      The study included 118 patients (120 eyes) examined before and after successful
      IMH surgery. The patients underwent electroretinography (Ganzfeld and
      multifocal), static computed perimetry, and optical coherence tomography. They
      were also tested for the electrical sensitivity of the retina, lability of the
      visual analyzer, and critical fusion frequency. Postoperative functional
      parameters of the retina (electrophysiological included) were followed up at 1-2,
      5-6, and 12-plus months and then compared to those obtained before surgery.
      Parameter dynamics, relationships, and the prognostic value of particular
      indicators were of interest. RESULTS: It was found that after successful
      restoration of retinal anatomy, functional parameters of the retina gradually
      improve and reach their maximum at 3 to 12 months, however, remain below the
      normal range in all cases. In 58 cases, postoperative visual acuity was 0.5 or
      higher (regarded as 'high postoperative visual acuity' - the HPVA group) and was
      accompanied by high density of foveal biopotential and foveal light sensitivity.
      In the HPVA group, the majority (62%) were patients with preoperative 'shift
      phenomenon' (a shift of the maximum of bioelectric potential from the fovea to
      parafovea and perifovea, its amplitude and density being supernormal for these
      retinal regions). CONCLUSION: Changes in electrophysiological and other
      functional parameters of the retina can be detected within 3-12 months after
      successful IMH surgery. Their recovery is not full and goes with a delay relative
      to restoration of retinal structure. The probability of high functional result of
      the operation, which includes an increase in visual acuity, foveal light
      sensitivity, and amplitude and density of foveal biopotential, is higher in
      patients with biopotential shift at baseline.

PMID- 29319671
TI  - [A modified implant for upper eyelid ptosis correction in frontalis suspension
      surgery].
AB  - AIM: to develop a modified implant to correct ptosis through brow suspension and
      to evaluate its effectiveness. MATERIAL AND METHODS: The clinical group consisted
      of 20 patients (29 eyes) aged 23 to 69 years (45+/-5.3 years on the average) and
      the comparison group - of 20 patients (33 eyes) aged 19 to 77 years (47+/-9.5
      years on the average). All patients were operated on for severe ptosis of the
      upper eyelid, which implied stitching their eyelids to the eyebrows. In the main
      group, an original implant was introduced as suspensory material - a 200 um thick
      porous polytetrafluoroethylene tape, length 13 cm, width 6 mm, round staggered
      perforation pattern, 1.5 mm holes, 3.5 mm pitch. In the comparison group,
      Mersilene mesh strips were used. The article contains a detailed description of
      the surgical technique. Checkups were performed at 1, 6, and 12 months. Follow-up
      periods were up to 4 years (1.7 years on the average) in the main group and up to
      7 years (5.1 years on the average) - in the controls. RESULTS: Were evaluated by
      the width of the palpebral fissure at raised eyebrows, marginal reflex distance
      (MRD, which is the distance between the center of the pupil and the upper eyelid
      margin), presence and depth of the upper eyelid crease, and residual
      lagophthalmos. Examinations held at months 1, 6, and 12 after surgery showed that
      the results were positive and stable in all cases. Neither signs of recurrence,
      nor statistically significant differences between the groups were found.
      CONCLUSION: The use of the original modified implant during frontalis suspension
      surgery provides high and stable cosmetic result and expands the possibilities of
      ophthalmic plastic surgery.

PMID- 29319672
TI  - [Objective assessment of donor material for penetrating corneal transplantation].
AB  - : Reliable suitability evaluation of donor material is the crucial issue of
      penetrating corneal transplantation. The main parameter to be considered is
      endothelial cell density (ECD). However, when it comes to practice, one has to
      admit significant variation in ECD readings of cadaver corneas obtained by
      different methods. AIM: to investigate discrepancies in ECD measurements and to
      define objective criteria for the evaluation of a donor cornea before full
      thickness grafting. MATERIAL AND METHODS: In a hundred cadaver eyes,
      discrepancies in ECD measurements by different methods (specular microscopy,
      confocal microscopy, and keratoanalyzer) were studied and objective evaluation
      criteria developed along with an optimal algorithm of pretransplantation
      assessment. Digital fluorescence microscopy was chosen as the reference method.
      RESULTS: It has been established that a triple measurement average obtained with
      any of the tested methods is informative enough as to the state of the donor
      cornea. CONCLUSION: The highest ECD values were obtained with specular
      microscopy, the lowest - with confocal microscopy. For reliable evaluation of
      donor corneas, we recommend that the average of a triple ECD measurement be taken
      using one of the mentioned methods.

PMID- 29319673
TI  - [Specifics of visual perception in infants with familial risk of autism spectrum
      disorders].
AB  - Preclinical prediction of autistic spectrum disorders (ASD) is one of the
      priorities of current research. Children at risk of ASD develop an atypical
      visual perception profile early in their lives, which influences their visual
      responsiveness, distribution of attention, and social orienting. In this study we
      have compared the oculomotor behavior in an infant at familial risk of ASD with
      data from two 10-month infants with typical development. The SMI RED500 eye
      tracker was used for acquisition. Most parameters of visual perception in the at
      risk infant were found to differ significantly from these of the controls. The
      strategy of visual search in the at-risk infant was generally less successful
      (13% of attempts vs 31% and 56% in the controls) with a tendency to focus
      predominantly on social stimuli (50% of the total gaze time). The said changes
      together with longer fixation duration (576.41 ms vs 527.77 and 386.72 ms in the
      two controls), lower saccadic frequency (1.74 counts/ms vs 1.84 and 2.18
      counts/ms), and shorter scan path length (2774.24 px vs 3612.58 and 3985.43 px)
      may result in difficulties in switching tasks and processing information.

PMID- 29319674
TI  - [Rate of visual recovery after macular hole surgery with intraoperative optical
      coherence tomography and visualization of the internal limiting membrane].
AB  - : Currently, multiple techniques exist to repair a macular hole, but the
      functional result may be largely affected by the use of dyes during surgery. With
      our original visualization methods, one is able to remove the internal limiting
      membrane (ILM) without staining, and thus to avoid the toxic effect of dyes. AIM:
      to compare anatomical and functional results of surgical closure of large macular
      holes with or without ILM staining. MATERIAL AND METHODS: A total of 160 patients
      (190 eyes) were divided into 2 groups. Patients from group 1 (60 eyes) were
      subjected to surgery that involved the use of a dye, while in group 2 (130 eyes)
      ILM was not performed. Anatomical and functional results of the two groups were
      then compared. RESULTS: The next day after surgery, a large improvement in the
      best corrected visual acuity - of 3 lines or more - was found in 28 controls
      (46.6%) and 98 patients from the main group (75.4%). There was no significant
      change in 24 and 27 patients, respectively (40.0% and 20.7%). The remaining 8 and
      5 patients (13.4% and 3.9%) deteriorated by 3 lines or more. CONCLUSION: Stain
      free removal of the ILM under green-yellow light favours rapid recovery of visual
      acuity in patients with macular holes. Anatomical reconstruction of the foveola,
      including complete approximation of the hole margins and keeping the defect
      closed until the end of the operation, is controlled through a built-in optical
      coherence tomograph ensuring high anatomical and functional results.

PMID- 29319675
TI  - [Use of infrared thermography in ophthalmology].
AB  - Thermoregulation disorders are associated with Body temperature fluctuation. Both
      hyper- and hypothermia are evidence of an ongoing pathological process.
      Contralateral symmetry in the Body heat spread is considered normal, while
      asymmetry, if above a certain level, implies an underlying pathology. Infrared
      thermography (IRT) is employed in many medical fields including ophthalmology.
      The earliest attempts of eye surface temperature evaluation were made in the 19th
      century. Over the last 50 years, different authors have been using this method to
      assess ocular adnexa, however, the technique remains insufficiently studied. The
      reported IRT data is often contradictory, which may be due to heterogeneity (in
      terms of severity) of patient groups and disparities between research parameters.

PMID- 29319676
TI  - [Fuchs endothelial corneal dystrophy].
AB  - Fuchs endothelial dystrophy is a severe disease characterized by slowly
      progressing bilateral asymmetric corneal edema usually seen in elderly patients.
      The primary purpose of treatment is to minimize edema-related symptoms, such as
      ocular discomfort and visual acuity loss. Conservative therapy is symptomatic and
      has a short-term positive effect that does not lead to full functional
      rehabilitation of the patient, while endothelial keratoplasty is pathogenetically
      oriented. Intentional replacement of pathologically altered corneal layers has
      several advantages: preservation of corneal architectonics, rapid recovery of
      visual function, 'closed eye' surgery with corneal tunnel approach, and
      independence from expensive equipment. However, principle indications and
      contraindications for various modifications of endothelial keratoplasty in the
      presence of comorbidity are still to be defined. Further improvement of the
      methods and their broader implementation into clinical practice are the most
      pressing and promising issues of corneal transplantation.

PMID- 29319677
TI  - [Corneal collagen cross-linking in the treatment of infectious keratitis and
      corneal ulcers].
AB  - In recent years, collagen cross-linking (CXL) of the cornea has acquired a new
      usage - in the treatment of infectious keratitis and corneal ulcers. This review
      was aimed at compiling the previously published data and assessing the
      effectiveness of the method.

PMID- 29319678
TI  - [Role of genetic markers in personalization of anti-angiogenic therapy in
      patients with exudative age-related macular degeneration].
AB  - The review presents data of clinical and pharmacogenetic research by Russian and
      foreign authors conducted within the last three years on the effectiveness of
      anti-angiogenic treatment against wet age-related macular degeneration (AMD).
      Scientific results on the association between angiogenesis-related gene
      polymorphisms responsible for predisposition to AMD on the one hand and a
      positive response to anti-VEGF therapy on the other are presented. Particular
      attention is paid to the main regulator of angiogenesis - the VEGF-A gene.

PMID- 29319679
TI  - [Ahmed valve in glaucoma surgery].
AB  - This is a review on Ahmed valve application in glaucoma surgery. It contains, in
      particular, data on the Ahmed valve efficiency, results of experimental and
      histological studies of filtering bleb encapsulation, examines the use of
      antimetabolites and anti-VEGF agents, and discusses implantation techniques. The
      current appraisal of antimetabolites delivery systems integrated into the Ahmed
      valve is presented. Various complications encountered in practice and preventive
      measures are also covered.

PMID- 29319680
TI  - [Idiopathic macular hole: history and status quo review].
AB  - The article reviews the literature on one of the topical problems of
      vitreoretinal surgery - idiopathic macular holes. The history, concept,
      classification and diagnostics, as well as surgical and alternative treatment
      methods of macular holes are explored.

PMID- 29319682
TI  - Bluebird's BCMA CAR-T impresses at ASH.

PMID- 29319681
TI  - [Economic aspects of diabetic macular edema treatment at regional level in
      Russian Federation].
AB  - An assessment of economic burden of Diabetic Macular Edema (DME) in Russian
      Federation was conducted on the example of four pilot regions including Samara
      Region, Republic of Bashkortostan, Chuvash Republic and Yaroslavl Region. The
      assessment involved a newly developed interactive pharmacoeconomic model that
      uses data from questionnaire surveys of leading DME experts residing in the
      regions. In the course of the study, direct and indirect costs associated with
      DME were calculated. The highest direct costs of DME treatment were seen in the
      Republic of Bashkortostan - 302 482 RUB/year per patient. Direct cost of treating
      a single DME patient in the Samara Region was 34 271 RUB/year, in the Yaroslavl
      Region - 32 308 RUB/year and in the Chuvash Republic - 12 243 RUB/year. Indirect
      costs per DME patient in the Samara Region amounted to 67 530 RUB/year, in the
      Yaroslavl Region - 75 177 RUB/year, in the Republic of Bashkortostan - 102 884
      RUB/year and in the Chuvash Republic - 81 082 RUB/year. Total annual costs per
      DME patient in the Samara Region was 101 801 RUB/year, in the Yaroslavl Region -
      107 485 RUB/year, in the Republic of Bashkortostan - 405 366 RUB/year and in the
      Chuvash Republic - 93 325 RUB/year.

PMID- 29319683
TI  - Why the European Union needs a national GMO opt-in mechanism.

PMID- 29319685
TI  - China's fledgling biotech sector fizzes into life.

PMID- 29319684
TI  - Mapping the global influence of published research on industry and innovation.

PMID- 29319686
TI  - Strength in numbers from integrated single-cell neuroscience.

PMID- 29319687
TI  - First in vivo human genome editing trial.

PMID- 29319688
TI  - Around the world in a month.

PMID- 29319689
TI  - Recent patents in proteomics.

PMID- 29319690
TI  - Texas displays 'Silicon Valley' credentials to lure Brazilian biotechs.

PMID- 29319691
TI  - Drugmakers cling to dual IL-13/IL-4 blockbuster hopes.

PMID- 29319692
TI  - FDA to relax grip on at-home genetic tests, but concerns linger.

PMID- 29319693
TI  - AI for your heart, on your wrist.

PMID- 29319695
TI  - PODCAST: First rounders: Susan Windham-Bannister.

PMID- 29319694
TI  - With a free pass, CRISPR-edited plants reach market in record time.

PMID- 29319697
TI  - FDA approves hereditary blindness gene therapy.

PMID- 29319696
TI  - RNA-targeting CRISPR comes of age.

PMID- 29319700
TI  - DNA makes an appearance.

PMID- 29319702
TI  - The structures of liquid pyridine and naphthalene: the effects of heteroatoms and
      core size on aromatic interactions.
AB  - Total neutron scattering has been used in conjunction with H/D and *N/15N
      isotopic substitution to determine the detailed liquid-state structures of
      pyridine and naphthalene. Analysis of the data via an empirical potential-based
      structure refinement method has allowed us to interrogate the full six
      dimensional spatial and orientational correlation surfaces in these systems, and
      thereby to deduce the fundamental effects of a heteroatom and aromatic core-size
      on intermolecular pi-pi interactions. We find that the presence of a nitrogen
      heteroatom, and concomitant dipole moment, in pyridine induces surprisingly
      subtle departures from the structural correlations observed in liquid benzene: in
      both cases the most probable local motif is based on perpendicular (edge-to-face)
      intermolecular contacts, while parallel-displaced configurations give rise to a
      clear shoulder in the correlation surface. However, the effect of the heteroatom
      is revealed through detailed analysis of the intermolecular orientational
      correlations. This analysis shows a tendency for neighbouring pyridine molecules
      to direct one meta- and one para-hydrogen towards the neighbouring aromatic pi
      orbitals in edge-to-face configurations, while head-to-tail alignment of adjacent
      nitrogen atoms is favoured in face-to-face configurations. In contrast to this,
      increasing aromatic core size from one to only two rings has a clear and profound
      effect on the pi-pi interactions and liquid structure. Our experiments show that
      naphthalene-naphthalene contacts are dominated by parallel-displaced
      configurations, akin to those found in graphite. This marks a fundamental
      difference with the structure of liquid benzene, in which perpendicular
      geometries are favoured. Furthermore, it is remarkable to note that in the
      systems studied, the most favoured spatio-orientational configurations observed
      in the liquid state are not predicted from ab initio calculations and/or solid
      state crystallographic studies. This highlights the need for caution when
      extrapolating the results of crystallographic and computational studies to
      aromatic interactions in liquids and disordered systems.

PMID- 29319699
TI  - Precision oncology in the age of integrative genomics.
AB  - Precision oncology applies genomic and other molecular analyses of tumor biopsies
      to improve the diagnosis and treatment of cancers. In addition to identifying
      therapeutic options, precision oncology tracks the response of a tumor to an
      intervention at the molecular level and detects drug resistance and the
      mechanisms by which it occurs. Integrative genomics can include sequencing
      specific panels of genes, exomes, or the entire triad of the patient's germline,
      tumor exome, and tumor transcriptome. Although the capabilities of sequencing
      technologies continue to improve, widespread adoption of genomics-driven
      precision oncology in the clinic has been held back by logistical, regulatory,
      financial, and ethical considerations. Nevertheless, integrative clinical
      sequencing programs applied at the point of care have the potential to improve
      the clinical management of cancer patients.

PMID- 29319703
TI  - Tailoring 2D and 3D molecular sieves structures for polyolefin composites: do all
      roads lead to remarkable performances?
AB  - Multiple synthetic strategies were performed in order to tether a zirconium-based
      catalyst to the 2D and 3D molecular sieves for olefin polymerizations. The
      anchoring of fluorene silane to the mesoporous MCM-41 was performed in order to
      obtain a stable catalyst for olefin polymerization (1@MCM-41). Using
      spectroscopic methods, this system was shown to have the metal center locked on a
      face down conformation with the surface. Also, immobilized zirconium complexes
      have been prepared on three different types of aminopropyl-modified supports
      (2@magadiite, 2@MCM-41 and 3@MCM-48). The advantage of this latter method of
      immobilization would be the reduction of the steric effect caused by the support:
      the catalyst, distant from the surface, is more exposed to the monomer and this
      situation may lead to an increase in the catalytic activity compared to 1@MCM-41.
      However, a medium size chain as a spacer between the support and the metallocene
      is still flexible enough to bend and predisposes the metal center to interact
      with the support surface; this effect is more evident when the nature of the
      support is of fixed pore dimensions. These supported catalysts exhibited activity
      for ethylene polymerization, resulting in linear PEs with high melting
      temperatures. In order to retain a metallocene assembled as in a homogeneous
      environment, a multi-step reaction was investigated (4@magadiite) but it led to
      the leaching of the organic moieties from the surface during catalyst
      preparation. The best catalytic performance was achieved when homogeneous Oct
      amido catalyst (5) was reacted with the surface of magadiite and n-alkyl-AlPO
      kan.

PMID- 29319704
TI  - Multiply "trapped" 3[trans-Pt(PR3)2(C[triple bond, length as m-dash]CC6H4X)2]*
      conformers in rigid media.
AB  - The complexes (R = Me, Et, Bu; X = H, SMe) exhibit well-defined multi-exponential
      emissions (2-4 components) in the solid state at 77 and 298 K and in 2MeTHF
      glasses at 77 K due to multiple frozen conformers exhibiting variable dihedral
      angles formed by the PtP2C2 and C6H4 planes. The demonstration was made using X
      ray crystallography at various temperatures where different sites are present in
      the samples, and using geometry optimization (DFT computations) where various
      stable conformers are noted.

PMID- 29319705
TI  - Structure, thermodynamics, and rearrangement mechanisms in gold clusters-insights
      from the energy landscapes framework.
AB  - We consider finite-size and temperature effects on the structure of model AuN
      clusters (30 <= N <= 147) bound by the Gupta potential. Equilibrium behaviour is
      examined in the harmonic superposition approximation, and the size-dependent
      melting temperature is also bracketed using molecular dynamics simulations. We
      identify structural transitions between distinctly different morphologies,
      characterised by various defect features. Reentrant behaviour and trends with
      respect to cluster size and temperature are discussed in detail. For N = 55, 85,
      and 147 we visualise the topography of the underlying potential energy landscape
      using disconnectivity graphs, colour-coded by the cluster morphology; and we use
      discrete path sampling to characterise the rearrangement mechanisms between
      competing structures separated by high energy barriers (up to 1 eV). The fastest
      transition pathways generally involve metastable states with multiple fivefold
      disclinations and/or a high degree of amorphisation, indicative of melting. For N
      = 55 we find that reoptimising low-lying minima using density functional theory
      (DFT) alters their energetic ordering and produces a new putative global minimum
      at the DFT level; however, the equilibrium structure predicted by the Gupta
      potential at room temperature is consistent with previous experiments.

PMID- 29319706
TI  - Dendritic polyelectrolytes revisited through the Poisson-Boltzmann-Flory theory
      and the Debye-Huckel approximation.
AB  - The properties of a dendritic polyelectrolyte in equilibrium with a reservoir of
      monovalent salts are investigated using the cell model and the Poisson-Boltzmann
      Flory theory. Within this approach we use the Debye-Huckel approximation to solve
      the Poisson-Boltzmann equation and minimize the semi-grand potential of the
      system with respect to the size of the molecule which enables us to inspect its
      conformations as well as the electric field, the ionic density profile, the
      overall charge density, the effective charge of the dendrimer and the osmotic
      pressure based on their response to the salt concentration and the dendrimer
      charge. The model predicts pronounced trapping of salt ions, a local charge
      neutrality and a zero electric field in the volume of the molecule as well as
      oscillations of the density profiles and the electric field in the vicinity of
      the dendrimer-bulk interface. As a result of ion trapping and screening of
      Coulomb interactions monovalent salts are found to have a minor effect on the
      size of the dendrimer. Specifically, the dendrimer exists in slightly swollen
      states as compared to the neutral molecule which indicates that the
      conformational properties of the polyelectrolyte depend weakly on monovalent
      salts. These observations harmonise with the equilibrium behavior of the
      dendrimer pressure, the internal pressure and the bulk pressure, respectively.

PMID- 29319707
TI  - Li0.93V2.07BO5: a new nano-rod cathode material for lithium ion batteries.
AB  - The compound Li0.93V2.07BO5 (LVBO) has been successfully designed and used for
      the first time as a cathode material for lithium ion batteries (LIBs). It belongs
      to a new family of lithium transition metal borates, namely LiMBO3 (M = Mn, Fe or
      Co), which are regarded as good alternatives to phosphates because of their
      comparably lower molecular weights, which can lead to a larger theoretical
      specific capacity than those of phosphate-based LiMPO4. LVBO crystallizes in the
      space group Pbam with V atom and Li atom occupying the same sites, which makes
      the structure more stable and brings a disorder effect. Further structure and
      components of the promising cathode material have been characterized based on the
      results of X-ray diffraction, X-ray photoelectron spectroscopy, Raman
      spectroscopy and inductively coupled plasma mass spectrometry. The synthesized
      LVBO/C material displays a nanorod morphology with a size of 20-100 nm and shows
      good electrochemical activity. When used as cathode material in LIBs, LVBO/C
      delivers an initial discharge specific capacity of 125 mA h g-1 and exhibits
      relatively good cycle stability. These results are of great interest for further
      study of its electrochemical behaviors, which is of significance in exploring new
      borate cathode materials for LIBs.

PMID- 29319708
TI  - Thermally induced alloying processes in a bimetallic system at the nanoscale:
      AgAu sub-5 nm core-shell particles studied at atomic resolution.
AB  - Alloying processes in nanometre-sized Ag@Au and Au@Ag core@shell particles with
      average radii of 2 nm are studied via high resolution Transmission Electron
      Microscopy (TEM) imaging on in situ heatable carbon substrates. The bimetallic
      clusters are synthesized in small droplets of superfluid helium under fully inert
      conditions. After deposition, they are monitored during a heating cycle to 600 K
      and subsequent cooling. The core-shell structure, a sharply defined feature of
      the TEM High-Angle Annular Dark-Field images taken at room temperature, begins to
      blur with increasing temperature and transforms into a fully mixed alloy around
      573 K. This transition is studied at atomic resolution, giving insights into the
      alloying process with unprecedented precision. A new image-processing method is
      presented, which allows a measurement of the temperature-dependent diffusion
      constant at the nanoscale. The first quantification of this property for a
      bimetallic structure <5 nm sheds light on the thermodynamics of finite systems
      and provides new input for current theoretical models derived from bulk data.

PMID- 29319709
TI  - Displacement of eta5-cyclopentadienyl ligands from half-sandwich C,C-(NHC
      cyanoalkyl)-nickel(ii) metallacycles: further insight into the structure of the
      resulting Cp-free nickelacycles and a catalytic activity study.
AB  - Four cationic C,C-(NHC-cyanoalkyl)-nickel(ii) metallacyclic complexes, [Ni{Me-NHC
      CH2CH(CN)}(NCMe)](PF6) (2a), [Ni{Mes-NHC-CH2CH(CN)}(NCMe)](PF6) (2b), [Ni{Mes-NHC
      (CH2)2CH(CN)}(NCMe)](PF6) (2c) and [Ni{DiPP-NHC-(CH2)2CH(CN)}(NCMe)](PF6) (2d),
      were prepared by the removal of the Cp ligand under acidic conditions at 0 
      degrees C from the corresponding half-sandwich nickelacycles [NiCp{R-NHC
      (CH2)nCH(CN)}] (1a-1d; Cp = eta5-C5H5; n = 1 or 2; R-NHC-(CH2)nCH(CN) = 1-R-3
      [(CH2)nCH(CN)]-imidazol-2-ylidene). Full characterization of 2a-d by 1H and
      13C{1H} NMR spectroscopy in CD3CN and pyridine-d5, ATR-FTIR spectroscopy, mass
      spectrometry, and CHN microanalyses established the presence of only one
      acetonitrile ligand per nickel atom in the solid state. A DFT structural study
      conducted on the cations of the methyl-substituted 5-membered nickelacycle 2a and
      the mesityl-substituted 6-membered cycle 2c found a small energetic cost (DeltaG
      = 7-12 kcal mol-1) for the loss of one acetonitrile ligand from the square-planar
      structures existing in solution, that should be easily amenable upon solvent
      evaporation (DeltaG? = 14 kcal mol-1 in the case of 2c). Two structures with one
      acetonitrile ligand could be optimized in both cases: (i) a truly T-shaped 14
      electron structure with an end-on acetonitrile ligand, and (ii) a masked T-shaped
      structure stabilized by the pi-coordination of the dangling CN group of the
      metallated alkyl chain, the latter being favoured by 2.4 kcal mol-1 in the case
      of the flexible 6-membered ring 2c. A comparison of calculated vibrational
      frequencies with experimental FTIR spectra ruled out pi-coordination of the
      dangling CN group as a nu(C[triple bond, length as m-dash]N) band at low
      frequency was absent. Complexes 2a-d thus probably exist as rare three-coordinate
      T-shaped 14-electron species in the solid state. Their catalytic activity was
      studied for the direct arylation of azoles, and 2c proved to be moderately active
      for the coupling of benzothiazole with aryl iodides. Mechanistic insights suggest
      that competing processes or a radical process catalysed by nickel particles could
      follow an initial reduction of 2c by the dimerization of a sacrificial amount of
      benzothiazole.

PMID- 29319710
TI  - Nanoassembly of quantum emitters in hexagonal boron nitride and gold nanospheres.
AB  - The assembly of quantum nanophotonic systems with plasmonic resonators is
      important for fundamental studies of single photon sources as well as for on-chip
      information processing. In this work, we demonstrate the controllable
      nanoassembly of gold nanospheres with ultra-bright narrow-band quantum emitters
      in 2D layered hexagonal boron nitride (hBN). We utilize an atomic force
      microscope (AFM) tip to precisely position gold nanospheres to close proximity to
      the quantum emitters and observe the resulting emission enhancement and
      fluorescence lifetime reduction. The extreme emitter photostability permits
      analysis at high excitation powers, and delineation of absorption and emission
      enhancement caused by the plasmonic resonators. A fluorescence enhancement of
      over 300% is achieved experimentally for quantum emitters in hBN, with a
      radiative quantum efficiency of up to 40% and a saturated count rate in excess of
      5 * 106 counts per s. Our results are promising for the future employment of
      quantum emitters in hBN for integrated nanophotonic devices and plasmonic based
      nanosensors.

PMID- 29319711
TI  - On skin microrelief and the emergence of expression micro-wrinkles.
AB  - Over the course of a life time, as a result of adaptive mechanobiological
      processes (e.g. ageing), or the action of external physical factors such as
      mechanical loading, the human skin is subjected to, and hosts complex biophysical
      processes. These phenomena typically operate through a complex interplay, that,
      ultimately, is responsible for the evolutive geometrical characteristics of the
      skin surface. Wrinkles are a manifestation of these effects. Although numerous
      theoretical models of wrinkles arising in multi-layered structures have been
      proposed, they typically apply to idealised geometries. In the case of skin,
      which can be viewed as a geometrically complex multi-layer assembly, it is
      pertinent to question whether the natural skin microrelief could play a
      significant role in conditioning the characteristics of compression-induced micro
      wrinkles by acting as an array of geometrical imperfections. Here, we explore
      this question through the development of an anatomically-based finite strain
      parametric finite element model of the skin, represented as a stratum corneum
      layer on top of a thicker and softer substrate. Our study suggests that skin
      microrelief could be the dominant factor conditioning micro-wrinkle
      characteristics for moderate elastic modulus ratios between the two layers.
      Beyond stiffness ratios of 100, other factors tend to overwrite the effects of
      skin microrelief. Such stiffness ratio fluctuations can be induced by changes in
      relative humidity or particular skin conditions and can therefore have important
      implications for skin tribology.

PMID- 29319712
TI  - 3-D and electrically conducting functional skin mapping for biomedical
      applications.
AB  - Ex situ and in situ 3-D and electrically conducting mapping of the skin
      topography via electropolymerization of a conducting polymer on a previously
      sampled skin stamp or directly on the skin of a live human subject were performed
      here with the intention to be further used in biomedical applications.

PMID- 29319713
TI  - Adaptable liquid crystal elastomers with transesterification-based bond exchange
      reactions.
AB  - Adaptable liquid crystal elastomers (LCEs) have recently emerged to provide a new
      and robust method to program monodomain LCE samples. When a constant stress is
      applied with active bond exchange reactions (BERs), polymer chains and mesogens
      gradually align in the strain direction. Mesogen alignment is maintained after
      removing the BER stimulus (e.g. by lowering the temperature) and the programmed
      LCE samples exhibit free-standing two-way shape switching behavior. Here, a new
      adaptable main-chain LCE system was developed with thermally induced
      transesterification BERs. The network combines the conventional properties of
      LCEs, such as an isotropic phase transition and soft elasticity, with the dynamic
      features of adaptable network polymers, which are malleable to stress relaxation
      due to the BERs. Polarized Fourier transform infrared measurements confirmed the
      alignment of polymer chains and mesogens after strain-induced programming. The
      influence of the creep stress, temperature, and time on the strain amplitude of
      two-way shape switching was examined. The LCE network demonstrates an innovative
      feature of reprogrammability, where the reversible shape-switching memory of
      programmed LCEs is readily deleted by free-standing heating as random BERs
      disrupt the mesogen alignment, so LCEs are reprogrammed after returning to the
      polydomain state. Due to the dynamic nature of the LCE network, it also exhibits
      a surface welding effect and can be fully dissolved in the organic solvent, which
      might be utilized for green and sustainable recycling of LCEs.

PMID- 29319714
TI  - Solvent-mediated aggregate formation of PNDIT2: decreasing the available
      conformational subspace by introducing locally highly ordered domains.
AB  - The high-mobility n-type donor/acceptor polymer PNDIT2 is well-known to form
      aggregates in solution depending on the solvent used. To gain additional insight
      into this process, we probed the local environment of triplet excitons in two
      different solvents and with two different polymer chain lengths using time
      resolved electron paramagnetic resonance (TREPR) spectroscopy. Results clearly
      show aggregation to introduce a high degree of local order in the polymer and to
      dramatically enhance the delocalisation of the exciton. Furthermore, triplet
      exciton delocalisation is only affected by the solvent used and hence by
      aggregate formation, not by chain length. Finally, aggregation changes the mode
      of delocalisation from intrachain to interchain when forming aggregates, the
      latter mode dominating as well in thin films. Taken together, TREPR proves to be
      a valuable tool for investigating aggregation and order in polymers on a
      molecular length-scale, ideally complementing preceding optical data.

PMID- 29319715
TI  - Identification and return of a skull from Tasmania in the Berlin anatomical
      collection.
AB  - ABSTRACT: Following a request by the Australian government, human remains of
      Australian origin were identified in the anatomical collection of Charite, the
      medical faculty of Berlin. We initiated an interdisciplinary provenance research
      on such remains to ensure their identity, elucidate their history, and prepare
      for a possible return to Australia. Here, we present results regarding a skull in
      the collection labeled as stemming from Tasmania. The non-invasive
      anthropological investigation revealed the skull to stem from a girl of about 15
      years of age who most likely died of a massive otitis/petrositis with subsequent
      meningitis. These results match the historical findings, which started from an
      inscription on the frontal bone giving a first name ("Nanny"), an ancestry
      ("native of Kangaroo Island"), a collector ("Schayer"), and a location ("van
      Diemensland", i.e. Tasmania). The collector, Adolph Schayer, was a German sheep
      breeder and botanical/zoological collector living in north-western Tasmania from
      1831 to 1843. In archival sources, a girl named Nanny Allan could be identified,
      who was a native of Kangaroo Island and died in Launceston/Tasmania in 1836 at
      the age of about 14 years. As there were no doubts that these remains stem from a
      Tasmanian individual, they were handed over to representatives of the Tasmanian
      Aboriginal Centre in July 2014.

PMID- 29319716
TI  - Screening protocol for dysphagia in adults: comparison with videofluoroscopic
      findings.
AB  - OBJECTIVES: To compare the videofluoroscopic findings of patients with suspected
      oropharyngeal dysphagia with the results of a clinical screening protocol.
      METHODS: A retrospective observational cohort study was conducted on all
      consecutive patients with suspected oropharyngeal dysphagia between March 2015
      and February 2016 who were assigned to receive a videofluoroscopic assessment of
      swallowing. All patients were first submitted to videofluoroscopy and then to the
      clinical assessment of swallowing. The clinical assessment was performed within
      the first 24 hours after videofluoroscopy. The videofluoroscopy results were
      analyzed regarding penetration/aspiration using an 8-point multidimensional
      perceptual scale. The accuracy of the clinical protocol was analyzed using the
      sensitivity, specificity, likelihood ratios and predictive values. RESULTS: The
      selected sample consisted of 50 patients. The clinical protocol presented a
      sensitivity of 50% and specificity of 95%, with an accuracy of 88%. "Cough" and
      "wet-hoarse" vocal quality after/during swallowing were clinical indicators that
      appeared to correctly identify the presence of penetration/aspiration risk.
      CONCLUSION: The clinical protocol used in the present study is a simple, rapid
      and reliable clinical assessment. Despite the absence of a completely
      satisfactory result, especially in terms of the sensitivity and positive
      predictive values, we suggest that lower rates of pneumonia can be achieved using
      a formal dysphagia screening method.

PMID- 29319717
TI  - Serum 25-hydroxyvitamin D levels in patients with Granulomatosis with
      Polyangiitis: association with respiratory infection.
AB  - OBJECTIVES: To determine the possible association of serum 25-hydroxyvitamin D
      (25OHD) levels with disease activity and respiratory infection in granulomatosis
      with polyangiitis patients during two different periods: winter/spring and
      summer/autumn. METHODS: Thirty-two granulomatosis with polyangiitis patients were
      evaluated in the winter/spring, and the same patients (except 5) were evaluated
      in summer/autumn (n=27). The 25OHD levels were measured by radioimmunoassay.
      Disease activity was assessed by the Birmingham Vasculitis Activity Score
      Modified for Wegener's Granulomatosis (BVAS/WG) and antineutrophil cytoplasmic
      antibody (ANCA) positivity. Respiratory infection was defined according the
      Centers for Disease Control and Prevention criteria. RESULTS: 25OHD levels were
      lower among patients in winter/spring than in summer/autumn (32.31+/-13.10 vs.
      38.98+/-10.97 ng/mL, p=0.04). Seven patients met the criteria for respiratory
      infection: 5 in winter/spring and 2 in summer/autumn. Patients with respiratory
      infection presented lower 25OHD levels than those without infection (25.15+/
      11.70 vs. 36.73+/-12.08 ng/mL, p=0.02). A higher frequency of low vitamin D
      levels (25OHD<20 ng/mL) was observed in patients with respiratory infection
      (37.5% vs. 7.8, p=0.04). Serum 25OHD levels were comparable between patients with
      (BVAS/WG>=1 plus positive ANCA) and without disease activity (BVAS/WG=0 plus
      negative ANCA) (35.40+/-11.48 vs. 35.34+/-13.13 ng/mL, p=0.98). CONCLUSIONS:
      Lower 25OHD levels were associated with respiratory infection but not disease
      activity in granulomatosis with polyangiitis patients. Our data suggest that
      hypovitaminosis D could be an important risk factor for respiratory infection in
      granulomatosis with polyangiitis patients.

PMID- 29319718
TI  - Effects of periarticular injection on analgesic effects and NSAID use in total
      knee arthroplasty and total hip arthroplasty.
AB  - OBJECTIVES: This study examined periarticular multimodal drug injection and the
      use of nonsteroidal anti-inflammatory drugs for an early analgesic effect after
      total knee arthroplasty and total hip arthroplasty. Patient satisfaction and
      benefits from the treatment were also assessed. METHODS: A total of 110 patients
      who were scheduled to undergo total knee arthroplasty and 86 patients who were
      scheduled to undergo total hip arthroplasty were divided into two groups, the
      study group and the control group. The study group received a periarticular
      multimodal drug injection during surgery. The control group received an equal
      volume of normal saline. All patients received an analgesia pump and a moderate
      dose of nonsteroidal anti-inflammatory drugs. Resting and motion Numeric Rating
      Scale scores, the Western Ontario and McMaster Universities Arthritis Index, knee
      or hip joint range of motion, length of postoperative hospital stay, patient
      satisfaction, total nonsteroidal anti-inflammatory drug consumption and side
      effects were recorded. RESULTS: Both study groups exhibited significant
      improvement in pain Numeric Rating Scale scores during rest and exercise several
      days after the surgery. The range of joint motion was greater in the study group,
      and the length of postoperative hospital stay was shorter than that in the
      control group. Patients in the study group consumed fewer nonsteroidal anti
      inflammatory drugs and reported greater satisfaction with surgery. CONCLUSION:
      Intraoperative periarticular multimodal drug injection significantly relieved
      pain after surgery and reduced nonsteroidal anti-inflammatory drug consumption.
      These patient had a better postoperative experience, including satisfaction and
      rehabilitation.

PMID- 29319719
TI  - A new low-cost negative-pressure wound therapy versus a commercially available
      therapy device widely used to treat complex traumatic injuries: a prospective,
      randomized, non-inferiority trial.
AB  - OBJECTIVES: Negative-pressure wound therapy has been widely adopted to reduce the
      complexity of treating a broad range of acute and chronic wounds. However, its
      cost is high. The objective of this study was to evaluate the following two
      different methods of negative-pressure wound therapy in terms of healing time: a
      low-cost method of negative-pressure wound therapy (a pressure stabilizer device
      connected to a hospital wall-vacuum system with a gauze-sealed dressing, USP) and
      the standard of care (vacuum-assisted closure, VAC). METHODS: This is a
      randomized, controlled, non-inferiority, unblinded trial. Patients admitted with
      complex injuries to a trauma center in a public referral hospital who were
      indicated for orthopedic surgery were randomized to a USP or VAC group. The
      primary outcome was the time required to achieve a "ready for surgery condition",
      which was defined as a wound bed with healthy granulation tissue and without
      necrosis or purulent secretion. Wound bed area contraction, granulation tissue
      growth and the direct costs of the dressings were secondary outcomes. RESULTS:
      Variation in area and granulation tissue growth were essentially the same between
      the systems, and healing time was equal between the groups (p=0.379). In both
      systems, serial debridement increased wound area (p=0.934), and granulation
      tissue was also increased (p=0.408). The mean treatment cost was US$ 15.15 in the
      USP group and US$ 872.59 in the VAC group. CONCLUSIONS: For treating complex
      traumatic injuries, USP was non-inferior to and less expensive than VAC.

PMID- 29319720
TI  - Depression and adherence to antiretroviral treatment in HIV-positive men in Sao
      Paulo, the largest city in South America: Social and psychological implications.
AB  - OBJECTIVES: The aim of the present study was to investigate the prevalence of
      depression and adherence to antiretroviral treatment in two groups of
      individuals: men who have sex with men (MSM) and men who have sex with women
      (MSW). METHODS: Two hundred and sixteen participants (MSM=116; MSW=100) who
      visited the Clinics Hospital of the School of the Medicine of the University of
      Sao Paulo completed two independent surveys (the BECK Depression Inventory and an
      adherence self-declared questionnaire) to evaluate their depression status and
      adherence to antiretroviral treatment, respectively. RESULTS: The study
      highlighted a positive relationship between depression and low adherence to
      Highly Active Antiretroviral Therapy in these patients regardless of age and
      sexual orientation. In addition, MSM subjects were two times more prone than MSW
      subjects to develop depression symptoms. White or mixed race men showed 7.6 times
      greater adherence to treatment than black men. The probability of complete
      adherence to treatment was 3.8 times higher in non-depressed subjects than in
      depressed subjects regardless of their ethnicity. The chance of developing
      depression was 4.17 times higher for an individual with non-adherent behavior
      than for an adherent individual. CONCLUSIONS: Individuals with low adherence
      rates have proportionally higher depression rates. Depressed men tend to show
      less adherence to treatment. Black but not mixed race or white men show less
      adherence to Highly Active Antiretroviral Therapy and have a greater chance of
      developing depression, which directly interferes with adherence. The chances of
      developing depression are four times greater for a patient with non-adherent
      behavior than for a patient with adherent behavior.

PMID- 29319721
TI  - Microcirculation improvement after short-term infusion of vasopressin in septic
      shock is dependent on noradrenaline.
AB  - OBJECTIVES: To assess the impact of vasopressin on the microcirculation and to
      develop a predictive model to estimate the probability of microcirculatory
      recruitment in patients with septic shock. METHODS: This prospective
      interventional study included patients with septic shock receiving noradrenaline
      for less than 48 hours. We infused vasopressin at 0.04 U/min for one hour.
      Hemodynamic measurements, including sidestream dark-field imaging, were obtained
      immediately before vasopressin infusion, 1 hour after vasopressin infusion and 1
      hour after vasopressin withdrawal. We defined patients with more than a 10%
      increase in total vascular density and perfused vascular density as responders.
      ClinicalTrials.gov: NCT02053675. RESULTS: Eighteen patients were included, and
      nine (50%) showed improved microcirculation after infusion of vasopressin. The
      noradrenaline dose was significantly reduced after vasopressin (p=0.001) and was
      higher both at baseline and during vasopressin infusion in the responders than in
      the non-responders. The strongest predictor for a favorable microcirculatory
      response was the dose of noradrenaline at baseline (OR=4.5; 95% CI: 1.2-17.0;
      p=0.027). For patients using a noradrenaline dose higher than 0.38 mcg/kg/min,
      the probability that microcirculatory perfusion would be improved with
      vasopressin was 53% (sensitivity 78%, specificity 77%). CONCLUSIONS: In patients
      with septic shock for no longer than 48 h, administration of vasopressin is
      likely to result in an improvement in microcirculation when the baseline
      noradrenaline dose is higher than 0.38 mcg/kg/min.

PMID- 29319722
TI  - Pain and quality of life in breast cancer patients.
AB  - OBJECTIVE: To evaluate the influence of pain on quality of life in breast cancer
      patients. METHODS: A cross-sectional study of 400 patients, including 118 without
      metastasis, 160 with loco-regional metastasis and 122 with distant metastasis.
      The instruments used were the European Organization for Research and Treatment
      for Cancer Quality of Life Questionnaire-Core 30 and the Breast Cancer-specific
      23 and short McGill Pain Questionnaire. RESULTS: In total, 71.7% of patients
      reported pain. The most frequent sensory descriptor used by patients was
      'jumping.' In the evaluative dimension, the main descriptor chosen was
      troublesome. The Global Health self-assessment showed pain to be inversely
      correlated with quality of life: the group without metastasis had a mean score of
      55.3 (SD=24.8) for those in pain, which rose to 69.7 (SD=19.2) for those without
      pain (p=0.001). Subjects with loco-regional metastasis had score of 59.1
      (SD=21.3) when in pain, and those without pain had a significantly higher score
      of 72.4 (SD=18.6) (p<0.001). Patients from the distant metastasis group showed
      similar results with a mean score of 48.6 (SD=23.1) for those in pain and 67.6
      (SD=20.4) for those without pain (p=0.002). Regarding the association of pain
      intensity and quality of life, patients with distant metastasis and intense pain
      had the worst scores for quality of life with a functional scale mean of 49.9
      (SD=17.3) (p<0.009), a Symptom Scale score of 50.0 (SD=20.1) (p<0.001) and a
      Global Health Scale score of 39.7 (SD=24.7) (p<0.006). CONCLUSIONS: Pain
      compromises the quality of life of patients with breast cancer, particularly
      those with advanced stages of the disease.

PMID- 29319723
TI  - Characteristics and Outcomes of Intensive Care Unit Survivors: Experience of a
      Multidisciplinary Outpatient Clinic in a Teaching Hospital.
AB  - OBJECTIVES: To describe the experience of an outpatient clinic with the
      multidisciplinary evaluation of intensive care unit survivors and to analyze
      their social, psychological, and physical characteristics in a low-income
      population and a developing country. METHODS: Retrospective cohort study. Adult
      survivors from a general intensive care unit were evaluated three months after
      discharge in a post-intensive care unit outpatient multidisciplinary clinic over
      a period of 6 years (2008-2014) in a University Hospital in southern Brazil.
      RESULTS: A total of 688 out of 1945 intensive care unit survivors received care
      at the clinic. Of these, 45.2% had psychological disorders (particularly
      depression), 49.0% had respiratory impairments (abnormal spirometry), and 24.6%
      had moderate to intense dyspnea during daily life activities. Patients
      experienced weight loss during hospitalization (mean=11.7%) but good recovery
      after discharge (mean gain=9.1%), and 94.6% were receiving nutrition orally. One
      third of patients showed a reduction of peripheral muscular strength, and 5.7%
      had moderate to severe tetraparesis or tetraplegia. There was a significant
      impairment in quality of life (SF-36), particularly in the physical and emotional
      aspects and in functional capacity. The economic impacts on the affected
      families, which were mostly low-income families, were considerable. Most patients
      did not have full access to rehabilitation services, even though half of the
      families were receiving financial support from the government. CONCLUSIONS: A
      significant number of intensive care unit survivors evaluated 3 months after
      discharge had psychological, respiratory, motor, and socioeconomic problems;
      these findings highlight that strategies aimed to assist critically ill patients
      should be extended to the post-hospitalization period and that this problem is
      particularly important in low-income populations.

PMID- 29319724
TI  - Evaluation of the efficacy and safety of endovascular management for transplant
      renal artery stenosis.
AB  - OBJECTIVES: To evaluate the safety and efficacy of endovascular intervention with
      angioplasty and stent placement in patients with transplant renal artery
      stenosis. METHODS: All patients diagnosed with transplant renal artery stenosis
      and graft dysfunction or resistant systemic hypertension who underwent
      endovascular treatment with stenting from February 2011 to April 2016 were
      included in this study. The primary endpoint was clinical success, and the
      secondary endpoints were technical success, complication rate and stent patency.
      RESULTS: Twenty-four patients with transplant renal artery stenosis underwent
      endovascular treatment, and three of them required reinterventions, resulting in
      a total of 27 procedures. The clinical success rate was 100%. All graft
      dysfunction patients showed decreased serum creatinine levels and improved
      estimated glomerular filtration rates and creatinine levels. Patients with high
      blood pressure also showed improved control of systemic blood pressure and
      decreased use of antihypertensive drugs. The technical success rate of the
      procedure was 97%. Primary patency and assisted primary patency rates at one year
      were 90.5% and 100%, respectively. The mean follow-up time of patients was 794.04
      days after angioplasty. CONCLUSION: Angioplasty with stent placement for the
      treatment of transplant renal artery stenosis is a safe and effective technique
      with good results in both the short and long term.

PMID- 29319725
TI  - Experimental implantation of an arterial substitute made of silicone reinforced
      with polyester fabric in rabbits.
AB  - OBJECTIVES: The aim of this study was to analyze silicone tubes with an internal
      diameter of 4 mm as a possible material for vascular prostheses. METHODS: Grafts
      were implanted into the infrarenal aortas of 33 rabbits. Fluoroscopic
      examinations were performed within 150 days after surgical implantation. Sample
      grafts were analyzed via electron microscopy to evaluate the eventual
      endothelialization of the prostheses. RESULTS: The patency rates of the
      prostheses were 87% (+/-6.7%) after 30 days, 73% (+/-9.3%) after 60 days and 48%
      (+/-12%) after 120 days. The material presented characteristics that support
      surgical implantation: good tolerance promoted by polyester tear reinforcement,
      ease of postoperative removal and a lack of pseudoaneurysms. However, intimal
      hyperplasia was a limiting factor for the patency rate. CONCLUSIONS: We concluded
      that polydimethylsiloxane has limited potential as an alternative material for
      small vascular prostheses.

PMID- 29319727
TI  - Risk factors for the prognosis of pediatric medulloblastoma: a retrospective
      analysis of 40 cases.

PMID- 29319726
TI  - Second hand tobacco smoke adversely affects the bone of immature rats.
AB  - OBJECTIVES: To evaluate the influence of secondhand cigarette smoke exposure on
      longitudinal growth of the tibia of growing rats and some parameters of bone
      quality. METHODS: Forty female rats were randomly divided into four groups:
      control: rats were sham exposed; 30 days: rats were exposed to tobacco smoke for
      30 days; 45 days: rats were exposed to tobacco smoke for 45 days; and 60 days:
      rats were exposed to tobacco smoke for 60 days. Blood samples were collected to
      evaluate the levels of cotinine and alkaline phosphatase. Both tibias were
      dissected and weighed; the lengths were measured, and the bones were then stored
      in a freezer for analysis of bone mineral content and mechanical resistance
      (maximal load and stiffness). RESULTS: Exposure of rats to tobacco smoke
      significantly compromised bone health, suggesting that the harmful effects may be
      time dependent. Harmful effects on bone growth were detected and were more
      pronounced at 60-day follow-ups with a 41.8% reduction in alkaline phosphatase
      levels (p<0.01) and a decrease of 11.25% in tibia length (p<0.001). Furthermore,
      a 41.5% decrease in bone mineral density was observed (p<0.001), leading to a
      42.8% reduction in maximum strength (p<0.001) and a 56.7% reduction in stiffness
      (p<0.001). CONCLUSION: Second hand cigarette smoke exposure in rats affected
      bones that were weaker, deforming them and making them osteopenic. Additionally,
      the long bone was shorter, suggesting interference with growth. Such events seem
      to be related to time of exposure.

PMID- 29319728
TI  - Cholecystectomy during ceftriaxone therapy. A translational study with a new
      rabbit model.
AB  - PURPOSE: To evaluate the actual incidence of both microlithiasis and acute
      cholecystitis during treatment with intravenous ceftriaxone in a new rabbit
      model. METHODS: New Zealand rabbits were treated with intravenous ceftriaxone or
      saline for 21 days. Ultrasound monitoring of the gallbladder was performed every
      seven days until the 21st day when histopathology, immunohistochemistry for
      proliferating cell nuclear antigen (PCNA), pro-caspase-3 and CD68, liver enzyme
      biochemistry, and chromatography analysis of the bile and sediments were also
      performed. RESULTS: All animals treated with ceftriaxone developed acute
      cholecystitis, confirmed by histopathology (P<0.05) and biliary microlithiasis,
      except one that exhibited sediment precipitation. In the group treated with
      ceftriaxone there was an increase in pro-caspase-3, gamma-glutamyl transpeptidase
      concentration, PCNA expression and in the number of cells positive for anti-CD68
      (P<0.05). In the ceftriaxone group, the cholesterol and lecithin concentrations
      increased in the bile and a high concentration of ceftriaxone was found in the
      microlithiasis. CONCLUSION: Ceftriaxone administered intravenously at therapeutic
      doses causes a high predisposition for lithogenic bile formation and the
      development of acute lithiasic cholecystitis.

PMID- 29319729
TI  - Effects of nivolumab in peritoneal carcinamatosis of malign melanoma in mouse
      model.
AB  - PURPOSE: To evaluate the efficacy of nivolumab and comparison with dacarbazine
      (DTIC) on peritoneal carcinomatosis of malignant melanoma in mouse model.
      METHODS: Mouse skin melanoma cells was injected under the capsule of the
      peritoneal surface in the left side of the abdomen. On postoperative day ten,
      mouses randomised into three groups. Group 1: Control, Group 2: HIPEC
      (Hyperthermic intraperitoneal chemotherapy) with DTIC and Group 3: HIPEC with
      Nivolumab. After the sacrification on postoperative day fifteen, peritoneum
      evaluated macroscopically and histopathologically by using peritoneal regression
      grading score (PRGS). RESULTS: In the 15th day exploration, all animals developed
      extensive intraperitoneal tumor growth in Group 1. In Group 2 and Group 3 median
      tumor size was 0.7+/-0.3cm and 0.3+/-0.2cm respectively (p: 0.023). Peritoneal
      carcinomatosis index (PCI) were significantly lower in Group 3 than other groups
      (p: 0.019). The lowest total tumor nodules in group 3 was 4 +/- 2. The PGRS score
      was found significantly lower in Group 3 than other groups (p: 0.03). Lymphocytic
      response rate was found higher in the Group 3. CONCLUSIONS: It has been found
      that nivolumab significantly better than DTIC on peritoneal metastases of malign
      melanoma in mouse models. Nivolumab treatment gives promising results with
      pathological evidence in the treatment of metastatic disease of malignant
      melanoma.

PMID- 29319730
TI  - Effect of different commercial fat sources on brain, liver and blood lipid
      profiles of rats in growth phase.
AB  - PURPOSE: To investigate the fatty acid content of different fat sources and
      evaluate the effect of them on plasma and hepatic lipids and on the fatty acid
      profile of the brain tissue of Wistar rats. METHODS: Thirty male albino Wistar
      rats received for 59 days, the following diets: diet added of margarine with low
      content of polyunsaturated fatty acids (PUFA); diet added of margarine with high
      content of PUFA; diet added of butter; diet added of hydrogenated vegetable fat;
      diet added of soybean oil. Fatty acid profile of the lipid sources, blood and
      hepatic lipids fractions and fatty acid profile of the brain tissue were
      determined. RESULTS: Margarine consumption of provided different responses as to
      concentrations of blood and hepatic lipid fractions. Intake of butter and
      hydrogenated increased LDL-c/HDL-c ratio, being the steepest increase promoted by
      hydrogenated vegetable fat, which also raised LDL-c levels expressively. All fats
      used in the treatments reduced the cerebral concentration of docosahexaenoic acid
      when compared to soybean oil (control). CONCLUSION: The different fat sources
      commonly consumed by population provided different responses in vivo. This is
      particularly relevant considering the role of these lipids in the incidence and
      prevention of cardiovascular diseases.

PMID- 29319731
TI  - Comparison among bone marrow mesenchymal stem and mononuclear cells to promote
      functional recovery after spinal cord injury in rabbits.
AB  - PURPOSE: To investigate the efficacy of allogeneic mesenchymal stem-cells and
      autologous mononuclear cells to promote sensorimotor recovery and tissue rescue.
      METHODS: Female rabbits were submitted to the epidural balloon inflation method
      and the intravenous cells administrations were made after 8 hours or seven days
      after injury induction. Sensorimotor evaluation of the hindlimbs was performed,
      and the euthanasia was made thirty days after the treatment. Spinal cords were
      stained with hematoxylin and eosin. RESULTS: Both therapies given 8 hours after
      the injury promoted the sensorimotor recovery after a week. Only the group
      treated after a week with mononuclear cells showed no significant recovery at
      post-injury day 14. In the days 21 and 28, all treatments promoted significant
      recovery. Histopathological analysis showed no difference among the experimental
      groups. Our results showed that both bone marrow-derived cell types promoted
      significant sensorimotor recovery after injury, and the treatment made at least a
      week after injury is efficient. CONCLUSION: The possibilities of therapy with
      bone marrow-derived cells are large, increasing the therapeutic arsenal for the
      treatment of spinal cord injury.

PMID- 29319732
TI  - A fatal and metabolic experimental hemorrhagic shock in immature swine.
AB  - PURPOSE: To use blood lactate (BL) as an end-point metabolic marker for the begin
      resuscitation of volume replacement in experimental hemorrhagic shock. METHODS:
      Group I (n=7) was not bled (Control). Animals in Group II (n=7) were bled to a
      MAP of 30mmHg in thirty minutes. Hemodynamic and metabolic data were recorded at
      Baseline, at 30, 60 and 120 minutes after Baseline. The animals were intubated in
      spontaneous breathing (FIO2=0.21) with halothane. RESULTS: Group I all survived.
      In Group II all died; no mortality occurred before a BL<10mM/L. Beyond the end
      point all animals exhibited severe acidemia, hyperventilation and clinical signs
      of shock. Without treatment all animals died within 70.43+/-24.51 min of
      hypotension shortly after reaching an average level of BL 17.01+/-3.20mM/L.
      CONCLUSIONS: Swine's breathing room air spontaneously in hemorrhagic shock not
      treated a blood lactate over 10mM/L results fatal. The predictable outcome of
      this shock model is expected to produce consistent information based on possible
      different metabolic and hemodynamic patterns as far as the type of fluid and the
      timing of resuscitation in near fatal hemorrhagic shock.

PMID- 29319733
TI  - Biomechanic and histologic analysis of fibroblastic effects of tendon-to-bone
      healing by transforming growth factor beta1 (TGF-beta1) in rotator cuff tears.
AB  - PURPOSE: To evaluate the effect of transforming growth factor beta1 (TGF-beta1)
      on tendon-to-bone reconstruction of rotator cuff tears. METHODS: Seventy-two rat
      supraspinatus tendons were transected and reconstructed in situ. At 8 and 16
      weeks, specimens of three groups; that is control, L-dose (low dose), and H-dose
      (high dose) were harvested and underwent a biomechanical test to evaluate the
      maximum load and stiffness values. Histology sections of the tendon-to-bone
      interface were identified by hematoxylin-eosin or Masson trichrome stain.
      Collagen type III was observed by picric acid sirius red staining under polarized
      light. The level of insulin-like growth factor 1 (IGF-1) and vascular endothelial
      growth factor (VEGF) was measured by the enzyme-linked immunosorbent assay
      (ELISA) method. RESULTS: Collagen type III of the H-dose group had a significant
      difference in histology structure compared with the L-dose group (P<0.05). The
      maximum load and stiffness decreased significantly in the control group compared
      with the values of the L-dose and H-dose groups. The stiffness among the three
      groups differed significantly at the same postoperative time (P<0.05).
      Interestingly, progressive reestablishment of collagen type III affected tendon
      to-bone healing significantly in the later stages. CONCLUSION: The H-dose was
      associated with an increased collagen type III morphology stimulated by TGF
      beta1.

PMID- 29319734
TI  - A prototype single-port device for pressurized intraperitoneal aerosol
      chemotherapy. Technical feasibility and local drug distribution.
AB  - PURPOSE: To evaluate the technical feasibility and homogeneity of drug
      distribution of pressurized intraperitoneal aerosol chemotherapy (PIPAC) based on
      a novel process of intraperitoneal drug application (multidirectional
      aerosolization). METHODS: This was an in vivo experimental study in pigs. A
      single-port device was manufactured at the smallest diameter possible for
      multidirectional aerosolization of the chemotherapeutic drug under positive
      intraperitoneal pressure. Four domestic pigs were used in the study, one control
      animal that received multidirectional microjets of 9 mL/sec for 30 min and three
      animals that received multidirectional aerosolization (pig 02: 9 mL/sec for 30
      min; pigs 03 and 04: 3 mL/sec for 15 min). Aerosolized silver nitrate solution
      was applied for anatomopathological evaluation of intraperitoneal drug
      distribution. RESULTS: Injection time was able to maintain the pneumoperitoneum
      pressure below 20 mmHg. The rate of moderate silver nitrate staining was 45.4%
      for pig 01, 36.3% for pig 02, 36.3% for pig 03, and 72.7% for pig 04.
      CONCLUSIONS: Intra-abdominal drug distribution had a broad pattern, especially in
      animals exposed to the drug for 30 min. Our sample of only four animals was not
      large enough to demonstrate an association between aerosolization and a higher
      silver nitrate concentration in the stained abdominal regions.

PMID- 29319735
TI  - Tibial tunnel enlargement and joint instability after anterior cruciate ligament
      reconstruction. A prospective comparison between autograft and allograft.
AB  - PURPOSE: To investigate tibial tunnel widening and knee instability after ACL
      reconstruction with hamstring autograft or irradiated soft tissue allograft.
      METHODS: Eight-two patients were divided into two groups: autograft group and
      allograft group. Radiographic and clinical evaluations were performed. RESULTS:
      Seventy patients were followed up with median of 36.3 months (range 36-38
      months). Tibial tunnel widening was at or greater than 30% for nine patients in
      the autograft group and 15 patients in the allograft group (P = 0.0417). The
      average percentage of tibial tunnel widening was 26.7 +/- 4.0 % and 29.7 +/- 5.3
      % in autograft and allograft groups, respectively (P = 0.0090). Knee range of
      motion was not affected by the reconstruction operation or different grafts.
      Thigh atrophy improved significantly within 24 months after ACL reconstructions
      in both groups. ACL reconstruction with the allograft leaded to less knee
      stability than that with the autograft from one year after operation (P =
      0.0023). There was no significant difference between two groups with respect to
      Lysholm score (P = 0.1925) and Tegner score (P =0 .0918) at the final follow-up.
      CONCLUSION: The allograft group reported significantly more tibial tunnel
      widening and knee instability compared with the autograft group.

PMID- 29319736
TI  - New virtual tool for accurate evaluation of facial volume.

PMID- 29319737
TI  - A non-living, effective model for microvascular training.
AB  - PURPOSE: To introduce a nonliving microvascular training model based on vessels
      diameter and feasibility. METHODS: We dissected ten oxen tongues, and divided the
      pedicles into three-thirds: proximal, middle and distal. We measured the external
      vessels diameter in all regions. We performed a descriptive statistical analysis.
      Three students (two beginner level and one intermediate level) performed this
      training. We evaluated the confidence, according Likert scale. RESULTS: We
      dissected all oxen tongues, each tongue showed two parallel pedicles. Each
      pedicle was located at 1.5 - 2.0 cm from the midline. Proximal median artery and
      vein diameter were 3.9 +/- 0.7, and 5.04 +/- 1.44mm, respectively. In the middle
      third, the mean artery diameter was 3.3 +/- 0.4mm, and the vein diameter was 3.5
      +/- 0.9mm. The distal third showed a mean artery diameter of 2.0 +/- 0.42mm, and
      a vein diameter of 2.4 +/- 0.82mm. The students performed ten anastomoses. This
      study showed a higher confidence level (CL) (p=0.03) than the pre training CL
      assessment. CONCLUSION: This study suggested a feasible non-animal model for
      microsurgical training process for beginners and intermediate trainees.

PMID- 29319738
TI  - The use of nanoparticles in wound treatment: a systematic review.
AB  - OBJECTIVE: To analyze the effects of nanoparticle-based dressings on the wound
      healing process in in vitro animals and human cells based on scientific evidence.
      METHOD: A systematic review of the literature in LILACS, PubMed and Science
      Direct databases. The articles were selected and evaluated for the level of
      evidence by the application of STROBE. RESULTS: The sample consisted of 12
      articles. The application of the products occurred in surgical wounds, burns,
      infected wounds and gingival ulcers in laboratory animals, as well as in vitro
      tests, demonstrating that among other advantages, the nanoparticle-based
      dressings increased the healing speed, had good antibacterial capacity and were
      non cytotoxic agents. CONCLUSION: Based on the analyzed articles, it can be
      affirmed that dressings containing nanocomposites are quite promising and are
      shown as a great therapeutic option in wound healing.

PMID- 29319739
TI  - Translation, cultural adaptation and validation of the Diabetes Attitudes Scale -
      third version into Brazilian Portuguese.
AB  - OBJECTIVE: to perform the translation, adaptation and validation of the Diabetes
      Attitudes Scale - third version instrument into Brazilian Portuguese. METHODS:
      methodological study carried out in six stages: initial translation, synthesis of
      the initial translation, back-translation, evaluation of the translated version
      by the Committee of Judges (27 Linguists and 29 health professionals), pre-test
      and validation. The pre-test and validation (test-retest) steps included 22 and
      120 health professionals, respectively. The Content Validity Index, the analyses
      of internal consistency and reproducibility were performed using the R
      statistical program. RESULTS: in the content validation, the instrument presented
      good acceptance among the Judges with a mean Content Validity Index of 0.94. The
      scale presented acceptable internal consistency (Cronbach's alpha = 0.60), while
      the correlation of the total score at the test and retest moments was considered
      high (Polychoric Correlation Coefficient = 0.86). The Intra-class Correlation
      Coefficient, for the total score, presented a value of 0.65. CONCLUSION: the
      Brazilian version of the instrument (Escala de Atitudes dos Profissionais em
      relacao ao Diabetes Mellitus) was considered valid and reliable for application
      by health professionals in Brazil.

PMID- 29319740
TI  - Pregnancy complications in Brazilian puerperal women treated in the public and
      private health systems.
AB  - OBJECTIVE: to analyze the prevalence of pregnancy complications and
      sociodemographic profile of puerperal patients with complications, according to
      the form of financing of the childbirth service. METHOD: cross-sectional study
      with interview of 928 puerperal women whose childbirth was financed by the
      Unified Health System, health plans and private sources (other sources than the
      Unified Health System). The sample was calculated based on the births registered
      in the Information System on Live Births, stratified by hospital and form of
      financing of the childbirth service. Data were analyzed using the chi-square and
      Fisher's exact tests. RESULTS: the prevalence was 87.8% for all puerperal women,
      with an average of 2.4 complications per woman. In the case of deliveries covered
      by the Unified Health System, urinary tract infection (38.2%), anemia (26.0%) and
      leucorrhea (23.5%) were more frequent. In turn, vaginal bleeding (26.4%), urinary
      tract infection (23.9%) and leucorrhoea (23.7%) were prevalent in deliveries that
      were not covered by the Unified Health System. Puerperal women that had their
      delivery covered by the Unified Health System reported a greater number of
      intercurrences related to infectious diseases, while women who used health plans
      and private sources reported intercurrences related to chronic diseases. A higher
      frequency of puerperal adolescents, non-white women, and women without partner
      among those assisted in the Unified Health System (p < 0.001). CONCLUSION: the
      high prevalence of complications indicates the need for monitoring and preventing
      diseases during pregnancy, especially in the case of pregnant women with
      unfavorable sociodemographic characteristics.

PMID- 29319741
TI  - Verbal abuse and mobbing in pre-hospital care services in Chile.
AB  - OBJECTIVE: to determine the perception of verbal abuse and mobbing and the
      associated factors of paramedic technicians (nursing assistants) and
      professionals (nurses, midwives, kinesiologists) in the pre-hospital care areas
      of three regions in the south of Chile. METHODS: descriptive and correlational
      study was performed within the professional community and a two-stage sample of
      the paramedic technician population in three regions. The questionnaire
      "workplace violence in the health sector" (spanish version) was applied after
      signing the informed consent. RESULTS: 51.4% of professionals and 46.6% of
      paramedic technicians consider they have been verbally abused during last year.
      17.6% of paramedic technicians and 13.5% of professionals perceived mobbing. A
      low percentage of these events are reported. In only one case of mobbing, the
      aggressor was legally penalized. No significant differences were found between
      the job categories and the studied regions. CONCLUSIONS: A high percentage of
      participants in each group perceived verbal abuse and non-minor percentage
      perceived mobbing, but most of these events are not reported.

PMID- 29319742
TI  - Risk prediction and impaired tactile sensory perception among cancer patients
      during chemotherapy.
AB  - OBJECTIVES: to estimate the prevalence of impaired tactile sensory perception,
      identify risk factors, and establish a risk prediction model among adult patients
      receiving antineoplastic chemotherapy. METHOD: historical cohort study based on
      information obtained from the medical files of 127 patients cared for in the
      cancer unit of a private hospital in a city in Minas Gerais, Brazil. Data were
      analyzed using descriptive and bivariate statistics, with survival and
      multivariate analysis by Cox regression. RESULTS: 57% of the 127 patients
      included in the study developed impaired tactile sensory perception. The
      independent variables that caused significant impact, together with time elapsed
      from the beginning of treatment up to the onset of the condition, were: bone,
      hepatic and regional lymph node metastases; alcoholism; palliative chemotherapy;
      and discomfort in lower limbs. CONCLUSION: impaired tactile sensory perception
      was common among adult patients during chemotherapy, indicating the need to
      implement interventions designed for early identification and treatment of this
      condition.

PMID- 29319743
TI  - Nursing Care Interpersonal Relationship Questionnaire: elaboration and
      validation.
AB  - OBJECTIVE: to elaborate an instrument for the measurement of the interpersonal
      relationship in nursing care through the Item Response Theory, and the validation
      thereof. METHOD: methodological study, which followed the three poles of
      psychometry: theoretical, empirical and analytical. The Nursing Care
      Interpersonal Relationship Questionnaire was developed in light of the Imogene
      King's Interpersonal Conceptual Model and the psychometric properties were
      studied through the Item Response Theory in a sample of 950 patients attended in
      Primary, Secondary and Tertiary Health Care. RESULTS: the final instrument
      consisted of 31 items, with Cronbach's alpha of 0.90 and McDonald's Omega of
      0.92. The parameters of the Item Response Theory demonstrated high discrimination
      in 28 items, being developed a five-level interpretive scale. At the first level,
      the communication process begins, gaining a wealth of interaction. Subsequent
      levels demonstrate qualitatively the points of effectiveness of the interpersonal
      relationship with the involvement of behaviors related to the concepts of
      transaction and interaction, followed by the concept of role. CONCLUSION: the
      instrument was created and proved to be consistent to measure interpersonal
      relationship in nursing care, as it presented adequate reliability and validity
      parameters.

PMID- 29319744
TI  - Urinary incontinence in hospital patients: prevalence and associated factors.
AB  - OBJECTIVES: to analyze the prevalence of urinary incontinence and its associated
      factors in hospital patients. METHOD: this is a cross-sectional epidemiological
      study whose data were collected using the instruments Sociodemographic and
      Clinical Data, Characteristics of Urinary Leakage and International Consultation
      on Incontinence Questionnaire - Short Form. Prevalence was surveyed on a single
      day for four consecutive months. Data were analyzed using Chi-square test,
      Fisher's exact test, Student t-test, Mann-Whitney test and logistic regression
      (forward stepwise). RESULTS: the final sample consisted of 319 hospital adults
      (57.1% female), mean age of 47.9 years (SD=21.1). The prevalence of urinary
      incontinence was 22.9% (28% in women and 16.1% in men) and the associated factors
      were: female sex (OR=3.89), age (OR=1.03), asthma (OR=3.66), use of laxatives
      (OR=3.26), use of diaper during the evaluation (OR=2.75), use of diaper at home
      (OR=10.29), and use of diaper at some point during the hospital stay (OR=6.74).
      CONCLUSION: the findings of this study differ from those found in the scarce
      existing literature on the subject in hospital patients. There is a need for
      previous studies such as this before proposing the implementation of preventive
      and therapeutic actions during the hospital stay.

PMID- 29319745
TI  - Short version of the "instrument for assessment of stress in nursing students" in
      the Brazilian reality.
AB  - GOAL: validate a short version of the Instrument for assessment of stress in
      nursing students in the Brazilian reality. METHOD: Methodological study conducted
      with 1047 nursing students from five Brazilian institutions, who answered the 30
      items initially distributed in eight domains. Data were analyzed in the R
      Statistical Package and in the latent variable analysis, using exploratory and
      confirmatory factor analyses, Cronbach's alpha and item-total correlation.
      RESULTS: The short version of the instrument had 19 items distributed into four
      domains: Environment, Professional Training, Theoretical Activities and
      Performance of Practical Activities. The confirmatory analysis showed absolute
      and parsimony fit to the proposed model with satisfactory residual levels. Alpha
      values per factor ranged from 0.736 (Environment) to 0.842 (Performance of
      Practical Activities). CONCLUSION: The short version of the instrument has
      construct validity and reliability for application to Brazilian nursing
      undergraduates at any stage of the course.

PMID- 29319746
TI  - Obesity, physical activity and prediabetes in adult children of people with
      diabetes.
AB  - OBJECTIVES: Determine prevalence of obesity / overweight, physical activity (PA)
      and prediabetes in adult children of parents with type 2 diabetes; identify
      differences according to sociodemographic variables, and describe the
      relationship of obesity/overweight with fasting glucose (FG) and glycosylated
      hemoglobin (A1C). METHODS: Cross-sectional study in 30 Mexican families with 53
      participating adult children. Obesity / overweight was determined with Body Mass
      Index (BMI), Waist Circumference (WC) and body fat percentage (BFP); PA with the
      short International Physical Activity Questionnaire (IPAQ), and prediabetes with
      FG. RESULTS: 64% of participants presented obesity / overweight, 32% low PA, and
      19% prediabetes. Men had higher WC than women (U= 219, p= 0.03). Women showed
      more BFP than men (U= 142, p <0.01). Blood glucose was related to BFP (rs= 0.336,
      p < 0.05), the A1C with the BMI (rs= 0.417, p <0.01), WC (rs= 0.394, p<0.01), BFP
      (rs= 0.494, p<0.01) and intense PA (rs= - 0.285, p<0.05). CONCLUSIONS: High
      prevalence of obesity / overweight and low PA were found. The FG was related only
      to BFP and A1C, in addition to BMI, WC and inversely with intense BP. It is
      recommended to modify the educational strategies of nursing at a family level.

PMID- 29319747
TI  - Effect of an orientation group for patients with chronic heart failure:
      randomized controlled trial.
AB  - OBJECTIVE: To evaluate the effect of the orientation group on therapeutic
      adherence and self-care among patients with chronic heart failure. METHOD:
      Randomized controlled trial with 27 patients with chronic heart failure. The
      intervention group received nursing consultations and participated in group
      meetings with the multi-professional team. The control group only received
      nursing consultations in a period of four months. Questionnaires validated for
      use in Brazil were applied in the beginning and in the end of the study to assess
      self-care outcomes and adherence to treatment. Categorical variables were
      expressed through frequency and percentage distributions and the continuous
      variables through mean and standard deviation. The comparison between the initial
      and final scores of the intervention and control groups was done through the
      Student's t-test. RESULTS: The mean adherence in the intervention group was 13.9
      +/- 3.6 before the study and 4.8 +/- 2.3 after the study. In the control group it
      was 14.2 +/- 3.4 before the study and 14.7 +/- 3.5 after the study. The self-care
      confidence score was lower after the intervention (p=0.01). CONCLUSION: The
      orientation group does not improve adherence to treatment and self-care
      management and maintenance and it may reduce confidence in self-care. Registry
      REBEC RBR-7r9f2m.

PMID- 29319748
TI  - Cross-cultural adaptation and validation of the Condom Self-Efficacy Scale:
      application to Brazilian adolescents and young adults.
AB  - OBJECTIVE: translate and adapt the Condom Self-Efficacy Scale to Portuguese in
      the Brazilian context. The scale originated in the United States and measures
      self-efficacy in condom use. METHOD: methodological study in two phases:
      translation, cross-cultural adaptation and verification of psychometric
      properties. The translation and adaptation process involved four translators, one
      mediator of the synthesis and five health professionals. The content validity was
      verified using the Content Validation Index, based on 22 experts' judgments.
      Forty subjects participated in the pretest, who contributed to the understanding
      of the scale items. The scale was applied to 209 students between 13 and 26 years
      of age from a school affiliated with the state-owned educational network. The
      reliability was analyzed by means of Cronbach's alpha. RESULTS: the Portuguese
      version of the scale obtained a Cronbach's alpha coefficient of 0.85 and the
      total mean score was 68.1 points. A statistically significant relation was found
      between the total scale and the variables not having children (p= 0.038), condom
      use (p= 0.008) and condom use with fixed partner (p=0.036). CONCLUSION: the
      Brazilian version of the Condom Self-Efficacy Scale is a valid and reliable tool
      to verify the self-efficacy in condom use among adolescents and young adults.

PMID- 29319749
TI  - The relationship between humidity, light and the activity pattern of a velvet
      worm, Epiperipatus sp. (Onychophora: Peripatidae), from Bahia Drake, South
      Pacific of Costa Rica.
AB  - Even though the Onychophora represent a whole phylum, observations of their
      activity pattern in nature are almost non-existent. Here we report on the
      relationship between humidity and light and activity pattern of a new species of
      velvet worm, genus Epiperipatus, from four years of field observations in the
      South Pacific of Costa Rica. We found that most activity occurs during the driest
      and darkest nights of the year, in contrast with theoretical predictions.

PMID- 29319750
TI  - Biological screening of extracts from leaf and stem bark of Croton floribundus
      Spreng. (Euphorbiaceae).
AB  - This work describes the preliminary evaluation of cytotoxic, antimicrobial,
      molluscicidal, antioxidant and anticholinesterase activities from leaf (LECF) and
      stem bark alcoholic extracts (BECF) of the species Croton floribundus Spreng.
      (Euphorbiaceae), popularly known as capixingui or tapixingui. BECF presented
      significant toxicity (LC50 = 89.6 MUg/ml) in the Artemia salina Leach, 1819
      (Crustacea: Branchiopoda) bioassay, whereas LECF did not show activity (LC50 >
      1000 MUg/ml). From DPPH method, the values of IC50 for the LECF and BECF were
      61.2 MUg/ml and 62.2 MUg/ml, respectively, showing that C. floribundus has an
      expressive antioxidant activity. Antimicrobial susceptibility was evaluated by
      microdilution technique and only BECF was active against Staphylococcus aureus
      (MIC = 39.6 MUg/ml). The extracts did not present molluscicidal activity against
      snail Biomphalaria glabrata Say, 1818 (Gastropoda: Planorbidae). Both extracts
      revealed the presence of several components with an inhibiting capacity of
      acetylcholinesterase enzyme on the bioautographic assay. C. floribundus showed to
      be a promising species considering that it exhibited good biological activity in
      the most assays performed.

PMID- 29319751
TI  - Effects of maternal high fat intake during pregnancy and lactation on total
      cholesterol and adipose tissue in neonatal rats.
AB  - AIM: Obesity during pregnancy is one of the most established risk factors for
      negative long-term programming. The aim of the present study was to investigate
      the effects of maternal consumption of a high-fat diet during pregnancy and
      lactation on the weight gain, visceral adipose tissue and cholesterolemia in
      neonatal rats. METHODS: Wistar rats were divided into two groups according to the
      mother's diet during pregnancy and lactation: Control group (CG, n = 12) were the
      offspring of rats fed a standard diet (4% lipid) and the Test group (TG, n = 12)
      were pups rats fed on a high fat diet (23% lipid). The weight of the animals was
      measured on alternate days until the 22nd day of life, when collected visceral
      adipose tissue and blood were collected for biochemical analysis. For statistical
      analysis the Student t test, Sidak's teste and two way ANOVA was used, with p
      <0.05. RESULTS: the test group showed differences in weight gain, visceral
      adipose tissue and higher cholesterol. CONCLUSION: a maternal exposure to a high
      fat diet during pregnancy and lactation can promote changes in weight gain,
      hypercholesterolemia and an increase in adipose tissue in neonatal rats.

PMID- 29319752
TI  - Effectiveness of aqueous and hydroalcoholic extracts of Acanthospermum australe
      (Loefl.) Kuntze against diarrhea-inducing bacteria.
AB  - Leaves and roots of Acanthospermum australe (Asteraceae) have been used in
      Brazilian folk medicine for the treatment of various ailments including diarrhea,
      skin diseases, blennorrhagia, dyspepsia, parasitic worms and malaria. The aim of
      study was to characterize the chemical profiles of the aqueous and hydroalcoholic
      extracts of leaves and roots of A. australe, and to evaluate their antimicrobial
      activities against diarrhea-inducing bacteria (Enterococcus faecalis, Shigella
      dysenteriae and Yersinia enterocolitica), as well as their cytotoxic properties.
      Aqueous leaf extracts were obtained by infusion, while aqueous root extracts were
      obtained by decoction. The hydroalcoholic leaf and root extracts were prepared by
      maceration in 90% ethanol for 3 days. Antimicrobial activity was assessed using
      standard techniques and cytotoxicity was evaluated using Chinese hamster ovary
      cells CHO-K1. Chemical analysis revealed the presence of tannins, flavonoids,
      saponins and phenolic compounds in the extracts. Although root extracts were not
      effective against E. faecalis, leaf extracts at concentrations of 20 mg/mL
      exhibited bactericidal activities against this microorganism. The hydroalcoholic
      root extract was unique in presenting a bactericidal effect against S.
      dysenteriae. None of the extracts showed bacteriostatic or bactericidal
      activities against Y. enterocolitica. The results presented herein demonstrate
      that the Gram-positive E. faecalis and the Gram-negative S. dysenteriae were
      susceptible to A. australe extracts, although bacteriostatic/bactericidal
      activities were only observed at concentrations considered too high for clinical
      application. Our results support the ethnopharmacological use of A. australe in
      the treatment of gastrointestinal disorders, particularly diarrhea caused by
      infectious bacteria, although further studies are required to determine the anti
      diarrhea effects and the toxicities of the extracts in vivo.

PMID- 29319753
TI  - Morphological characterization of insect galls and new records of associated
      invertebrates in a Cerrado area in Bahia State, Brazil.
AB  - In this study, we report the first records and morphological characterization of
      galls in a Cerrado area in western Bahia, Brazil. The data were collected monthly
      over two hours between March and September 2015. Fifteen gall morphotypes were
      found in twelve plant species distributed among seven families. The plant family
      with the greatest richness of galls was Fabaceae (n = 8). The following gall
      morphologies were found: globoid, lenticular, marginal leaf roll, conical,
      cylindrical, fusiform, spherical and pocket shaped. Cecidomyiidae induced
      globoid, lenticular, conical, fusiform, spherical and cylindrical morphotypes. In
      addition, species of microhymenoptera belonging to the Eulophidae, Eurytomidae
      and Encyrtidae families were found. Marginal leaf roll and pocket-shaped galls
      induced by Thysanoptera were also verified. Springtails were also identified as a
      successor. Undescribed species of Schizomyia and Lopesia were recorded in B.
      cupulata and Andira humilis, respectively.

PMID- 29319754
TI  - Identification and antimicrobial suceptibility profile of bacteria causing bovine
      mastitis from dairy farms in Pelotas, Rio Grande do Sul.
AB  - Mastitis is an inflammatory process of the udder tissue caused mainly by the
      bacteria Staphylococcus aureus. The indiscriminate use of antibiotics fosters
      conditions that favor the selection of resistant microorganisms, suppressing at
      the same time susceptible forms, causing a serious problem in dairy cattle. Given
      the importance in performing an antibiogram to select the most adequate
      antimicrobial therapy, the aim of this study was to identify bacteria isolated
      from cow's milk with mastitis, in dairy farms situated in the city of Pelotas,
      Rio Grande do Sul, and to determinate the susceptibility profile of these
      isolates against the antibiotics used to treat this illness. A total of 30
      isolates of Staphylococcus spp., were selected from milk samples from the udder
      quarters with subclinical mastitis whose species were identified through the
      Vitek system. The susceptibility profile was performed by the disk diffusion
      assay, against: ampicillin, amoxicillin, bacitracin, cephalexin, ceftiofur,
      enrofloxacin, gentamicin, neomycin, norfloxacin, penicillin G, tetracycline and
      trimethoprim. In the antibiogram, 100.0% of the isolates were resistant to
      trimethoprim and 96.7% to tetracycline and neomycin, three strains of
      Staphylococcus spp., (10.0%) presented resistance to the 12 antibiotics tested
      and 24 (80.0%) to at least eight. These results showed the difficulty in treating
      mastitis, due to the pathogens' resistance.

PMID- 29319755
TI  - First record of galls in the tree fern Cyathea phalerata (Cyatheaceae) from a
      Tropical Rainforest in Brazil.

PMID- 29319756
TI  - Predation of Sternopygus macrurus (Bloch & Schneider, 1801) by Micrurus
      surinamensis (Cuvier, 1817) in one fragment forest in Amazon, Brazil.

PMID- 29319757
TI  - Quality of life in the treatment of chronic kidney disease: a challenge.

PMID- 29319758
TI  - Cytomegalovirus infection after transplantation: prevention is still the
      challenge.

PMID- 29319759
TI  - Transthoracic pulmonary ultrasonography: looking inside the lungs to better treat
      the dialysis patient.

PMID- 29319760
TI  - Acute kidney injury in critically ill obstetric patients: a cross-sectional study
      in an intensive care unit in Northeast Brazil.
AB  - INTRODUCTION: Acute kidney injury (AKI) is a complication still poorly studied in
      the setting of obstetric patients, which is associated with increased mortality.
      Objective: The aim of this study was to investigate the frequency and risk
      factors of AKI among critically ill obstetric patients. METHODS: A cross
      sectional study was conducted with all patients admitted to an intensive care
      unit (ICU) due to obstetric complications, in Fortaleza, Brazil, in the period
      between January 2012 and December 2014. AKI was defined according to AKIN
      criteria. RESULTS: A total of 389 patients were included, aged between 13 and 45
      years. The main causes of ICU admission were pregnancy-related hypertensive
      syndromes (54.5%), hemorrhage and hemorrhagic shock (12.3%), heart diseases
      (9.0%), respiratory insufficiency (8.2%) and sepsis (5.4%). AKI was found in 92
      cases (24%), and this was the most frequent complication. General mortality was
      7.5%, and mortality due to AKI was 21% (p = 0.0007). In the multivariate
      analysis, risk factors for AKI were cesarian delivery (95% CI = 0.23-0.85, p =
      0.01) and thrombocythopenia (95% CI = 1.50-4.36, p = 0.001). AKI was an
      independent risk factor for death (OR = 6.64, 95% CI = 3.11-14.15, p < 0.001).
      CONCLUSION: AKI was the main complication among critically ill obstetric patients
      and it was associated with increased mortality. Most cases were associated with
      pregnancy-related hypertensive disorders, which are complications that can be
      easily identified and treated during prenatal care.

PMID- 29319761
TI  - Isotonic sports drink promotes rehydration and decreases proteinuria following
      karate training.
AB  - INTRODUCTION: Adequate hydration status in the sport is essential for good
      health, yet the relationship between hydration, proteinuria and sports is little
      studied. OBJECTIVE: To analyze the influence of an isotonic sports drink as
      rehydration strategy on the hydration status and proteinuria after karate
      training. METHODS: Ten athletes participated in this study. In the first session
      of standard training, called observation training session (STO), the athletes
      hydrated themselves according to their habits, and in the second session of
      standard training, called nutritional intervention training session (STIN), an
      ideal practice of hydration protocol was followed, using an isotonic sports drink
      as a rehydration liquid during the training. The hydration status was verified by
      monitoring the body weight before and after training, the urine specific gravity
      pre-and post-training and the urine volume post-training. To observe the
      influence of practice of hydration on the renal function post exercise
      proteinuria was measured. RESULTS: We observed a statistically significant
      difference in urine density between the samples pre- and post-exercise only on
      STIN (p = 0.047). When we compare the sessions, there was a lower variation in
      body weight (p = 0.011) and higher urinary volume (p < 0.001), on nutritional
      intervention training. In STO, there was a higher percentage of athletes who
      showed proteinuria (70%) compared to the STIN (50%) in the urine sample after
      training. CONCLUSION: The use of isotonic sports drink as practice of hydration
      by karate athletes promoted rehydration during one session of training and reduce
      post-training proteinuria.

PMID- 29319762
TI  - Complement System and C4d expression in cases of Membranous nephropathy.
AB  - INTRODUCTION: Membranous nephropathy (MN) is one of the major causes of nephrotic
      syndrome. The complement system plays a key role in the pathophysiology of MN.
      OBJECTIVES: To identify the complement pathway possibly activated in MN cases and
      correlate the presence of C4d with more severe clinical and histological markers.
      METHODS: Sixty nine cases from renal biopsy with membranous nephropathy were
      investigated. The presence of C1q was analyzed by direct immunofluorescence; and
      expression of C4d by immunohistochemistry. Clinical and epidemiological data were
      obtained upon biopsy request. RESULTS: The presence of focal segmental
      glomerulosclerosis, global glomerulosclerosis, vascular lesions and
      tubulointerstitial fibrosis were collected by anatomopathological report. C4d(+)
      was found in 58 (84%), and C1q(+) was found in 12 (17%) of the cases. Twelve
      patients had C4d(+)/C1q(+), 46 had C4d(+)/C1q(-), and 11 patients had C4d(-)/C1q(
      ), probably indicating the activation of the classical, lectin and alternative
      pathways, respectively. CONCLUSION: C4d was associated with increased
      interstitial fibrosis, but not with clinical markers of poor prognosis. Through
      the deposition of C4d and C1q we demonstrated that all complement pathways may be
      involved in MN, highlighting the lectin pathway. The presence of C4d has been
      associated with severe tubulointerstitial lesions, but not with clinical markers,
      or can be taken as a universal marker of all cases of MN.

PMID- 29319763
TI  - Current distribution pattern of biopsy-proven glomerular disease in Salvador,
      Brazil, 40 years after an initial assessment.
AB  - INTRODUCTION: A report on the prevalence of glomerular disease diagnosed via
      renal biopsy in Salvador, BA, Brazil was published in 1973 and showed a
      predominance of membranoproliferative glomerulonephritis, which was frequently
      associated with hepatosplenic schistosomiasis. OBJECTIVE: In this study, we
      investigate the potential changes in the distribution of glomerular diseases
      after a period of important epidemiological transition in Brazil. METHODS:
      Pathology reports of all patients subjected to kidney biopsy from 2003 to 2015 in
      a referral nephrology service were reviewed. Clinical, laboratorial and
      pathological diagnoses were collected for analysis. Histological slides of the
      biopsies performed between 2003 and 2006 were reviewed to examine the accuracy of
      the estimates based on the pathology reports. RESULTS: Among the biopsies
      performed during the time period, 1,312 met the inclusion criteria for the study.
      Focal and segmental glomerulosclerosis was the most prevalent diagnosis, followed
      by lupus nephritis. However, a trend toward a decrease in the prevalence of focal
      and segmental glomerulosclerosis was detected (p < 0.05), and an increase in
      lupus (p < 0.0001) and membranous glomerulonephritis (p < 0.005) was observed.
      CONCLUSION: The data presented herein suggest the occurrence of changes in the
      distribution of nephrological diseases in Salvador, Brazil. The disease that was
      most prevalent shifted from membranoproliferative glomerulonephritis to focal and
      segmental glomerulosclerosis from 1975 to 2006 and from focal and segmental
      glomerulosclerosis to lupus nephritis from 2006 to 2015.

PMID- 29319764
TI  - Prevalence of chronic kidney disease in a population in southern Brazil (Pro
      Renal Study).
AB  - INTRODUCTION: Chronic kidney disease (CKD) affects 10-12% of the adult population
      in many countries. In Brazil, there is no reliable information about the actual
      prevalence of CKD. OBJECTIVE: To determine the prevalence of CKD by estimated
      glomerular filtration rate (eGFR) and proteinuria/albuminuria in an urban
      population randomly selected in Southern Brazil. Patients and. METHODS: 5,216
      individuals were randomly selected out of a pool of 10,000 individuals identified
      from the database of a local energy company. The screening consisted of
      collection of demographic data, history of diabetes mellitus, hypertension,
      kidney/cardiovascular disease in the family and obesity through the body mass
      index - BMI (CKD risk factors). Blood samples were collected for determination of
      serum creatinine and subsequent eGFR estimation by the MDRD formula and urine
      samples for determination of albuminuria by dipstick. Albuminuria was further
      evaluated by HemoCue(c) in a selected CKD risk group. RESULTS: The population was
      predominantly Caucasians (93%), 64% were females and the mean age of participants
      was 45 years old (18-87). BMI (kg/m2) was 27+/-5. Albuminuria was found in 5.25%
      of individuals. 88.6% of this population had no CKD (eGFR > 60 ml/min/1.73m2 &
      normoalbuminuria) and 11.4% were identified as having CKD, with majority on
      stages 3A (7.2%) and 3B (1.1%). Hypertension, diabetes, older age and obesity was
      associated with a higher prevalence of CKD (p < 0.001). CONCLUSIONS: The
      prevalence of CKD in an urban population in southern Brazil mirrors other
      developed countries and indicates that kidney disease is an important public
      health problem in Brazil.

PMID- 29319765
TI  - Muscle thickness of the pectoralis major and rectus abdominis and level of
      physical activity in chronic hemodialysis patients.
AB  - INTRODUCTION: Patients on chronic hemodialysis tend to lose lean body mass and
      have sedentary behavior. OBJECTIVE: To compare the level of physical activity and
      the morphology of the muscles pectoralis major and rectus abdominis of patients
      on hemodialysis with healthy subjects. METHODS: We studied 17 patients and 17
      healthy individuals. Muscle thickness were evaluated by ultrasound, and the level
      of physical activity by the International Physical Activity Questionnaire (IPAQ),
      long version. RESULTS: The patients had lower thicknesses of the pectoralis major
      (5.92 +/- 0.35 mm vs. 8.35 +/- 0.62 mm, p < 0.001) and rectus abdominis (0.96 +/-
      0.10 mm vs. 2 21 +/- 0.40 mm, p < 0.001) compared to healthy subjects. Patients
      were physically less active than healthy individuals: 1502.55(788.19-2513.00) MET
      minutes/week vs. 2268.0(1680.0-4490,8) MET-minutes/week (p = 0.006); the weekly
      caloric expenditure of patients was also lower: 1384.0(480,7-2253.7) kcal/kg/week
      vs. 1680.0(1677.4-4950.0) kcal/kg/week (p = 0.010). The average time spent
      sitting per week of the patients was higher than in healthy subjects (394.0 +/-
      33.1 min/day vs. 293.0 +/- 38.6, p = 0.009) as well as the average time spent
      sitting during weekend (460.0 +/- 40.1 vs. 201.0 +/- 10.7, p = 0.003).
      CONCLUSION: Chronic renal failure patients on hemodialysis have sedentary
      behavior and lower muscle thickness of the trunk.

PMID- 29319766
TI  - EPIC Trial: education programme impact on serum phosphorous control in CKD 5D
      patients on hemodialysis.
AB  - INTRODUCTION: In stage 5D chronic kidney disease (CKD 5D) patients, the
      encouragement of treatment adherence by health professionals is a significant
      clinical challenge. OBJECTIVES: This study evaluates the impact of a nutritional
      education programme on hyperphosphatemia, utilizing the transtheoretical model of
      behavior change (TMBC). SUBJECTS AND METHODS: A prospective interventional study
      comprising 179 CKD 5D patients with hypophosphatemia. The 4-month educational
      programme took place during dialysis sessions. Demographic and laboratory data
      were evaluated, whilst the TMBC was utilized both pre- and post-intervention.
      RESULTS: 132 patients showed a positive change and significant reduction in
      phosphate levels, whilst 47 patients showed a negative change and little
      reduction in phosphate levels. Positive changes were identified at different
      levels of literacy. 117/179 participants had ongoing treatment with sevelamer
      throughout the trial period. 61 patients with intact parathyroid hormone (iPTH) <
      300pg/ml showed phosphate level reductions, whilst 118 patients with iPTH > 300
      pg/ml also showed a decrease in phosphate levels. CONCLUSIONS: Nutritional
      education programmes can achieve excellent results when appropriately applied. An
      education programme may be effective across different literacy levels.

PMID- 29319767
TI  - Variables associated with lung congestion as assessed by chest ultrasound in
      diabetics undergoing hemodialysis.
AB  - INTRODUCTION: Ultrasound is an emerging method for assessing lung congestion but
      is still seldom used. Lung congestion is an important risk of cardiac events and
      death in end-stage renal disease (ESRD) patients on hemodialysis (HD). OBJECTIVE:
      We investigated possible variables associated with lung congestion among
      diabetics with ESRD on HD, using chest ultrasound to detect extracellular lung
      water. METHODS: We studied 73 patients with diabetes as the primary cause of
      ESRD, undergoing regular HD. Lung congestion was assessed by counting the number
      of B lines detected by chest ultrasound. Hydration status was assessed by
      bioimpedance analysis and cardiac function by echocardiography. The collapse
      index of the inferior vena cava (IVC) was measured by ultrasonography. All
      patients were classified according to NYHA score. Correlations of the number of B
      lines with continuous variables and comparisons regarding the number of B lines
      according to categorical variables were performed. Multivariate linear regression
      was used to test the variables as independent predictors of the number of B
      lines. RESULTS: None of the variables related to hydration status and cardiac
      function were associated with the number of B lines. In the multivariate
      analysis, only the IVC collapse index (b = 45.038; p < 0.001) and NYHA classes (b
      = 13.995; p = 0.006) were independent predictors of the number of B lines.
      CONCLUSION: Clinical evaluation based on NYHA score and measurement of the
      collapsed IVC index were found to be more reliable than bioimpedance analysis to
      predict lung congestion.

PMID- 29319768
TI  - The current burden of cytomegalovirus infection in kidney transplant recipients
      receiving no pharmacological prophylaxis.
AB  - : Cytomegalovirus (CMV) infection in kidney transplantation has changed its
      clinical spectrum, mostly due to the current and more effective
      immunosuppression. In the absence of preventive strategies it is associated with
      significant morbi-mortality. OBJECTIVE: This study evaluated the incidence of CMV
      events and its effect on outcomes of kidney transplantation in recipients without
      pharmacological prophylaxis or targeted preemptive treatment. RESULTS: The study
      cohort comprised 802 recipients of kidney transplants between 04/30/2014 and
      04/30/2015. The majority received induction with anti-thymocyte globulin (81.5%),
      tacrolimus and prednisone in combination with either mycophenolate (46.3%) or
      azathioprine (53.7%). The overall incidence of CMV events was 42% (58.6%
      infection and 41.4% disease). Patients with CMV showed higher incidence of first
      treated acute rejection (19 vs. 11%, p = 0,001) compared with those without CMV
      but no differences in graft loss, death or loss to follow-up. The incidence of
      delayed graft function was higher (56% vs. 37%, p = 0.000) and the eGFR at 1 (41
      +/- 21 vs. 54 +/- 28 ml/min, p = 0.000) and 12 months (50 +/- 19 vs. 61 +/- 29
      ml/min, p = 0.000) were lower in patients with CMV. Recipients age (OR = 1.03),
      negative CMV serology (OR = 5.21) and use of mycophenolate (OR = 1.67) were
      associated with increased risk of CMV. Changes in immunosuppression was more
      often in patients with CMV (63% vs. 31%, p = 0.000). CONCLUSION: the incidence of
      CMV events was high and associated with higher incidence of acute rejection and
      changes in immunosuppression. Besides traditional risk factors, renal function at
      1 month was independently associated with CMV infection.

PMID- 29319769
TI  - Impact of an early physiotherapy program after kidney transplant during hospital
      stay: a randomized controlled trial.
AB  - INTRODUCTION: Cardiorespiratory and musculoskeletal dysfunctions are common in
      the postoperative period of kidney transplant patients and are often accompanied
      by low exercise tolerance. OBJECTIVE: The purpose of this study was to evaluate
      the impact of an early physiotherapy program during hospital stay on functional
      capacity and peripheral and respiratory muscle strength after kidney transplant.
      METHODS: An open, randomized clinical trial was conducted in patients undergoing
      living donor kidney transplant. Sixty-three patients were included (intervention
      group-IG: n = 30; control group-CG: n = 33). IG received an early physiotherapy
      program from first postoperative day until hospital discharge and CG received
      standard care. The variables of interest were measured preoperatively and at
      discharge except for respiratory muscle strength and vital capacity (VC), which
      were also measured on the first postoperative day. Functional capacity was
      evaluated through six-minute walk test (6MWT); peripheral and respiratory muscle
      strength using a dynamometer and manovacuometer, respectively; and VC through
      spirometer. RESULTS: After surgery, there was a reduction in functional walking
      capacity and peripheral muscle strength without different between groups (p >
      0.05); however, respiratory muscle strength was significantly higher in IG (p <
      0.001) at hospital discharge, when comparing with CG. CONCLUSIONS: An early
      physiotherapy program during hospitalization for patients undergoing living donor
      kidney transplant caused a lower reduction in respiratory muscle strength and
      without additional benefits in the functional capacity, when compared to a
      control group, although the clinical relevance of this finding is uncertain.

PMID- 29319770
TI  - Factors associated with hospital mortality in renal transplant patients admitted
      to the intensive care unit with acute respiratory failure.
AB  - INTRODUCTION: The lungs are often involved in a variety of complications after
      kidney transplantation. Acute respiratory failure (ARF) is one of the most
      serious manifestations of pulmonary involvement. OBJECTIVE: To describe the main
      causes of ARF in kidney transplant patients who require intensive care and
      identify the factors associated with mortality. METHODS: This retrospective study
      evaluated adult patients with ARF admitted to the intensive care unit of a center
      with high volume of transplants from August 2013 to August 2015. Demographic,
      clinical, and transplant characteristics were analyzed. Multivariate logistic
      regression analysis was performed to identify factors associated with hospital
      mortality. RESULTS: 183 patients were included with age of 55.32 +/- 13.56 years.
      126 (68.8%) were deceased-donor transplant, and 37 (20.2%) patients had previous
      history of rejection. The ICU admission SAPS3 and SOFA score were 54.39 +/- 10.32
      and 4.81 +/- 2.32, respectively. The main cause of hospitalization was community
      acquired pneumonia (18.6%), followed by acute pulmonary edema (15.3%).
      Opportunistic infections were common: PCP (9.3%), tuberculosis (2.7%), and
      cytomegalovirus (2.2%). Factors associated with mortality were requirement for
      vasopressor (OD 8.13, CI 2.83 to 23.35, p < 0.001), invasive mechanical
      ventilation (OD 3.87, CI: 1.29 to 11.66, p = 0.016), and SAPS3 (OD 1.04, CI 1.0
      to 1.08, p = 0.045). CONCLUSION: Bacterial pneumonia is the leading cause of ARF
      requiring intensive care, followed by acute pulmonary edema. Requirement for
      vasopressor, invasive mechanical ventilation and SAP3 were associated with
      hospital mortality.

PMID- 29319771
TI  - Peritoneal dialysis as the first dialysis treatment option initially unplanned.
AB  - Most patients with stage 5 CKD start RRT of unplanned manner. Unplanned dialysis,
      also known as urgent start, may be defined as hemodialysis (HD) started without
      permanent vascular access, i.e., using a central venous catheter (CVC), or as
      peritoneal dialysis (PD) started within seven days after implantation of the
      catheter, without family training. Although few studies have evaluated the PD as
      an immediate treatment option for patients starting urgent RRT, theirs results
      suggest that it is a feasible and safe alternative, with infectious complications
      and survival similar to patients treated with unplanned HD. Given the importance
      of the social role of urgent start of dialysis and the lack of studies on the
      subject, this narrative review aims to analyze and synthesize knowledge in
      published articles, preferably, from last five years in order to unify
      information and facilitate future studies.

PMID- 29319772
TI  - Clinical and histological features of patients with membranoproliferative
      glomerulonephritis classified by immunofluorescence findings.
AB  - BACKGROUND: New classification for membranoproliferative glomerulonephritis has
      been proposed in the literature. The aim of this study was to compare the
      clinical, biochemical, etiology and renal biopsy findings of these patients
      grouped by immunofluorescence as proposed by the new classification. METHODS:
      Patients with renal biopsy-proven membranoproliferative glomerulonephritis
      unrelated to systemic lupus erythematosus, diagnosed between 1999 and 2014. The
      patients were divided according to immunofluorescence: Immunoglobulin positive
      group, C3 positive only and negative immunofluorescence group. RESULTS: We
      evaluated 92 patients, the majority of which were in the immunoglobulin positive
      group. Infectious diseases, hepatitis C virus and schistosomiasis, were the most
      frequent etiology. A negative immunofluorescence group had more vascular
      involvement in renal biopsy compare with others groups. CONCLUSIONS: The only
      difference between the groups was higher vascular involvement in renal biopsy in
      negative immunofluorescence group. These new classification was satisfactory for
      the finding of etiology in one part of the cases.

PMID- 29319773
TI  - ANCA-Positive pauci-immune crescentic glomerulonephritis in a patient with
      systemic lupus erythematosus.
AB  - The pauci-immune crescentic glomerulonephritis (PICGN) is generally associated
      with small-vessel vasculitis with a few reported cases associated with other
      autoimmune diseases such as Systemic Lupus Erythematosus (SLE). We present the
      case of a female 34-year-old patient with acute kidney injury symptoms with
      indication for renal replacement therapy in the context of clinical SLE
      diagnosis. A kidney biopsy was conducted and it was found that most glomeruli
      showed some segmental sclerosis with synechia to the Bowman's capsule. 67% of the
      glomeruli had fibroepithelial crescents. Moreover, the interstitial space had a
      moderate lymphomononuclear infiltration and mild fibrosis. In the arterioles,
      there were walls thickened by subintimal sclerosis. Direct immunofluorescence
      detected limited IgM and C3 deposits in capillary loops and negative mensangium
      for IgG, IgA and C1q. A therapy using corticosteroids and intravenous
      cyclophosphamide was initiated with stable evolution. PICGN associated with SLE
      is a rare pathology with clinical presentation, varied evolution and without a
      standard medical treatment.

PMID- 29319774
TI  - Renal artery pseudoaneurysm.
AB  - The renal artery pseudoaneurysm embody a rare vascular complication coming of
      percutaneous procedures, renal biopsy, nephrectomy, penetrating traumas and more
      rarely blunt traumas. The clinical can be vary according the patient, the
      haematuria is the symptom more commom. Is necessary a high level of clinical
      suspicion for your diagnosis, this can be elucidated by through complementary
      exams as the eco-color Doppler and the computed tomography scan (CT). This report
      is a case of a patient submitted a right percutaneous renal biopsy and that,
      after the procedure started with macroscopic haematuria, urinary tenesmus and
      hypogastric pain. The diagnosis of pseudoaneurysm was given after one week of
      evolution when the patient was hospitalized because gross haematuria,
      tachycardia, hypotension and hypochondrium pain. In the angiotomography revealed
      a focal dilation of the accessory right renal inferior polar artery, dilation of
      renal pelvis and all the ureteral course with presence hyperdenso material
      (clots) inside the middle third of the ureter. The treatment for the majority of
      this cases are conservative, through arterial embolization, indicated for thouse
      of smaller dimensions in patients who are hemodynamically stable. However, it was
      decided by clinical treatment with aminocaproic acid 1 g, according to previous
      studies for therapy of haematuria. The patient received discharge without
      evidence of macroscopic haematuria and with normal renal ultrasound, following
      ambulatory care.

PMID- 29319775
TI  - Primary hiperoxaluria diagnosed after kidney transplantation: report of 2 cases
      and literature review.
AB  - Primary hyperoxaluria (PH) is a very rare genetic disorder; it is characterized
      by total or partial deficiency of the enzymes related to the metabolism of
      glyoxylate, with an overproduction of calcium oxalate that is deposited in
      different organs, mainly the kidney, leading to recurrent lithiasis,
      nephrocalcinosis and end stage renal disease (ESRD). In patients with ESRD that
      receive kidney transplantation alone, the disease has a relapse of 100%, with
      graft loss in a high percentage of patients in the first 5 years of
      transplantation. Three molecular disorders have been described in PH: mutation of
      the gene alanin glioxalate aminotransferase (AGXT); glyoxalate reductase/hydroxy
      pyruvate reductase (GRHPR) and 4-OH-2-oxoglutarate aldolase (HOGA1). We present
      two cases of patients with a history of renal lithiasis who were diagnosed with
      primary hyperoxaluria in the post-transplant period, manifested by early graft
      failure, with evidence of calcium oxalate crystals in renal biopsy,
      hyperoxaluria, hyperoxalemia, and genetic test compatible; they were managed with
      proper diet, abundant oral liquids, pyridoxine, hydrochlorothiazide and potassium
      citrate; however, they had slow but progressive deterioration of their grafts
      function until they reached end-stage chronic renal disease.

PMID- 29319776
TI  - Hypercalcemia and acute renal insufficiency following use of a veterinary
      supplement.
AB  - A previously healthy 24 yo male presented with a two-month history of epigastric
      pain, nausea, vomiting, fatigue and malaise. He reported abuse of different
      substances, including an injectable veterinary vitamin compound, which contains
      high doses of vitamin A, D and E, and an oily vehicle that induces local edema
      and enhances muscle volume. Serum creatinine was 3.1 mg/dL, alanine transaminase
      160 mg/dL, aspartate transaminase 11 mg/dL, total testosterone 23 ng/dL, 25-OH
      vitamin D >150 ng/mL (toxicity >100), 1,25-OH-vitamin D 80 pg/mL, vitamin A 0.7
      mg/dL, parathormone <3 pg/mL, total calcium 13.6 mg/dL, 24-hour urinary calcium
      635 mg/24h (RV 42-353). A urinary tract ultrasound demonstrated signs of
      parenchymal nephropathy. The diagnosis was hypercalcemia and acute renal failure
      secondary to vitamin D intoxication. He was initially treated with intravenous
      hydration, furosemide and prednisone. On the fifth day of hospitalization a dose
      of pamidronate disodium was added. The patient evolved with serum calcium and
      renal function normalization. Thirty days later he presented normal clinical and
      laboratory tests, except 25-OH-vitamin D that was persistently increased (107
      ng/mL), as it may take several months to normalize. This case report is a warning
      of the risks related to the use of veterinary substances for aesthetics purposes.

PMID- 29319777
TI  - Encapsulating peritoneal sclerosis: case report.
AB  - Patients with chronic kidney disease (CDK) can develop several diseases caused by
      the renal replacement therapy. Here we report a rare complication of peritoneal
      dialysis, the encapsulating peritoneal sclerosis (EPS) in which the peritoneal
      tissue is gradually replaced by fibrous tissue. The patient in question, after
      late loss of renal graft and conversion to peritoneal dialysis, evolved with
      multiple hospitalizations for spontaneous bacterial infections, in recent
      admission, he was diagnosed with sub-occlusive abdomen secondary to the EPS. Five
      days after, presented with intestinal obstruction requiring surgical approach by
      laparotomy, being performed with right colectomy, enterectomy, enteroraphy and
      ileostomy with drainage. The patient progressed well and follows on prednisone
      and tamoxifen-associated with intermittent hemodialysis.

PMID- 29319778
TI  - Granulomatous intersticial nephritis secondary to sarcoidosis.
AB  - INTRODUCTION: Granulomatous interstitial nephritis is a rare condition, in which
      renal involvement is uncommon. Its etiology is variable, and may be medicinal,
      infectious or inflammatory origin. CASE REPORT: This is a 65-year-old male
      patient with renal lesions of unknown etiology, associated with hypercalcaemia.
      During the investigation, cardiac insufficiency with diastolic dysfunction and
      interstitial lung involvement on chest tomography were evidenced. Renal function
      (glomerular filtration rate) has partially improved with clinical measures. Renal
      biopsy was performed, which showed moderate interstitial lesion with tuberculoid
      granulomas without caseous necrosis. CONCLUSION: The objective of the article was
      to describe a case of NIG and to alert to the importance of its clinical
      investigation. In this case, renal biopsy, associated with systemic clinical
      manifestations, contributed to the diagnosis of sarcoidosis.

PMID- 29319779
TI  - Recovery of renal function after bilateral renal vein thrombo sis episode as
      complication of membranous glomerulopa thy: case report.
AB  - Renal vein thrombosis (RVT) is a complication often associated with nephrotic
      syndrome. It occurs due to a state of hypercoagulability common in the diseases
      that attend to this syndromic diagnosis. It should be suspected whenever there is
      nephrotic syndrome associated with sudden flank pain, hematuria and worsening of
      proteinuria. Bilateral RVT also presents with frequently oliguric renal
      dysfunction. This case reports a 33-year-old patient hospitalized for a nephrotic
      syndrome, with etiologic investigation suggestive of primary membranous
      glomerulopathy, which evolved with bilateral RVT associated with deterioration of
      renal function and need for renal replacement therapy. He promptly performed
      angiography with thrombectomy and thrombolysis, evolving with recovery of renal
      function in two weeks.

PMID- 29319780
TI  - Diabetes mellitus and hyperkalemic renal tubular acidosis: case reports and
      literature review.
AB  - Hyporeninemic hypoaldosteronism, despite being common, remains an underdiagnosed
      entity that is more prevalent in patients with diabetes mellitus. It presents
      with asymptomatic hyperkalemia along with hyperchloraemic metabolic acidosis
      without significant renal function impairment. The underlying pathophysiological
      mechanism is not fully understood, but it is postulated that either aldosterone
      deficiency (hyporeninemic hypoaldosteronism) and/or target organ aldosterone
      resistance (pseudohypoaldosteronism) may be responsible. Diagnosis is based on
      laboratory parameters. Treatment strategy varies according to the underlying
      pathophysiological mechanism and etiology and aims to normalize serum potassium.
      Two clinical cases are reported and the relevant literature is revisited.

PMID- 29319781
TI  - A future for nephrology?
AB  - It is interesting that some of my predictions came true and some did not, but I
      think the jury is still out on many of them. I start to remind everyone on the
      glorious past of Nephrology, from the physiology, translational and
      methodological discoveries that have contributed to the development of our
      discipline. I predict that the Academic branch of Nephrology will continue to
      excel in three domains: Creative Research,Teaching (Training) and Innovative
      Clinical Care. I forsee dramatic changes in Nephrology practice in the short term
      (10 years) and I discuss which areas will have a most dramatic impact. Many
      developments will likely curtail the growth of CKD and decrease the burden of
      ESRD on society. The greatest challenge will be to ensure that what can be done
      to alleviate suffering and premature death from kidney disease will be done, in a
      cost-effective manner, and that all patients with kidney disease have reasonable
      and timely access to care for their illnesses. Nephrologists practicing in the
      second quarter of the 21st Century and beyond will be justifiably proud of their
      discipline, just as their predecessors have.

PMID- 29319782
TI  - TINU syndrome in a 14-year old boy.

PMID- 29319783
TI  - Commentary on: Dorsal Preservation: The Push Down Technique Reassessed.

PMID- 29319784
TI  - The effect of isabelin, a sesquiterpene lactone from Ambrosia artemisiifolia on
      soil microorganisms and human pathogens.
AB  - Ambrosia artemisiifolia L. (common ragweed) is an invasive weed, which is well
      known for the strong allergenic effect of its pollen as well as for its
      invasiveness and impact in crop fields (e.g. causing yield losses). This species
      produces a broad range of sesquiterpenoids. In recent years, new bioactive
      molecules have been discovered in this plant, e.g. isabelin, a sesquiterpene
      dilactone. The bioactivity of isabelin has been already demonstrated on allergy
      related receptors and its inhibitory effect on seeds of various plant species.
      Isabelin was tested for potential antimicrobial effects by using a selection of
      soil-borne bacteria and fungi and three human pathogens as model organisms. For
      the majority of microorganisms tested, no antimicrobial activity of isabelin was
      observed. However, isabelin revealed strong antimicrobial activity against the
      Gram-positive soil bacterium Paenibacillus sp. and against the Gram-positive,
      multidrug-resistant Staphylococcus aureus. The observed inhibitory activity of
      isabelin can enlighten the importance to study similar compounds for their effect
      on human pathogens and on soil and rhizosphere microorganisms.

PMID- 29319785
TI  - Diagnostic accuracy and prognostic value of simultaneous hybrid 18F
      fluorodeoxyglucose positron emission tomography/magnetic resonance imaging in
      cardiac sarcoidosis.
AB  - Aims: Cardiac death is the leading cause of mortality in patients with
      sarcoidosis, yet cardiac involvement often remains undetected. Cardiovascular
      magnetic resonance imaging (CMR) and 18F-fluorodeoxyglucose (FDG)-positron
      emission tomography (PET) have been used to diagnose cardiac sarcoidosis (CS) yet
      never simultaneously in a cohort. This study sought to assess the diagnostic and
      prognostic utility of simultaneous hybrid cardiac PET/MR. Methods and results:
      Fifty-one consecutive patients with suspected CS (age 50 +/- 13 years, 31 males)
      underwent simultaneous PET/MR following a high-fat/low-carbohydrate diet and 12-h
      fast. Blinded image analysis of FDG uptake and late gadolinium enhancement (LGE)
      was performed using the American Heart Association (AHA) 16-segment model. The
      sensitivity and specificity of PET/MR for diagnosing CS was estimated using the
      Japanese Ministry of Health and Welfare guidelines. The primary endpoint was a
      composite of death, aborted sudden cardiac death, sustained ventricular
      arrhythmia, complete heart block, and hospital admission with decompensated heart
      failure. The secondary endpoints were a fall in left ventricular ejection
      fraction (LVEF) >10%, non-sustained ventricular tachycardia and other cardiac
      related hospital admission. The prevalence of CS was 65% (n = 33). The
      sensitivity of PET and CMR alone for detecting CS was 0.85 and 0.82,
      respectively. Hybrid PET/MR was superior for detecting CS with sensitivity,
      specificity, positive, and negative predictive values of 0.94, 0.44, 0.76, and
      0.80, respectively. There was poor inter-modality agreement for the location of
      cardiac abnormalities (k = 0.02). Over the median follow-up of 2.2 years, there
      were 18 (35%) adverse events. Cardiac RV PET abnormalities and presence of LGE
      were independent predictors of adverse events. Abnormalities found on both PET
      and magnetic resonance imaging was the strongest predictor of major adverse
      cardiac events. Conclusion: Simultaneous PET/MR is an accurate method for
      diagnosing CS. FDG-PET and CMR combined offers complementary information on
      disease pathophysiology. The presence of LGE and FDG uptake on PET/MR identifies
      patients at higher risk of adverse events. PET and CMR should therefore be
      considered in the assessment of disease presence, stage, and prognosis in CS.

PMID- 29319786
TI  - A Transmissible Rash of Palms and Soles in a 58-Year-Old Man.

PMID- 29319787
TI  - Dorsal Preservation: The Push Down Technique Reassessed.
AB  - Management of the nasal dorsum remains a challenge in rhinoplasty surgery.
      Currently, the majority of reduction rhinoplasties results in destruction of the
      keystone area (K-area), which requires reconstruction with either spreader grafts
      or spreader flaps, both for aesthetic and functional reasons. This article will
      present the senior author's current operative technique for dorsal preservation
      in reduction rhinoplasty based on 320 clinical cases performed over a 5-year
      period. The author's operative technique is as follows: (1) endonasal approach;
      (2) removal of a septal strip in the subdorsal area whose shape and height were
      determined preoperatively; (3) complete lateral, transverse, and radix
      osteotomies; and (4) dorsal reduction utilizing either a push down operation
      (PDO) or a let down operation (LDO). The PDO consists of downward impaction of
      the fully mobilized nasal pyramid and is utilized in patients with smaller humps
      (Less than 4 mm). The LDO consists of a maxillary wedge resection and is
      performed in patients who need more than 4 mm of lowering. A total of 320
      patients had a dorsal preservation operation (DPO). Postoperatively, there were
      no dorsal irregularities nor inverted-V deformities. Among our 44 personal
      revision cases, 27 patients (8.74%) had had a previous DPO, 16 of whom required
      tip revisions with no further dorsal surgery. Of the remaining 11 patients, the
      main problems were either hump recurrence and/or lateral deviation of the dorsum
      or widening of the middle third, which required simple surgical revision. Based
      on the authors' experience, adoption of a PDO/LDO is justified in selected
      primary patients. The key question before any primary rhinoplasty procedure
      should be "Can I keep the nasal dorsum intact?" Precise analysis and surgical
      execution are required to preserve the dorsal osseocartilaginous vault and K
      area. Dorsal preservation results in more natural postoperative dorsum lines and
      a "not operated" aspect without the need for midvault reconstruction. Moreover,
      this technique is quick and easy to perform by any rhinoplasty surgeon.
      Rhinoplasty surgeons should consider incorporating dorsal preservation techniques
      in their surgical armamentarium rather than relying solely on the Joseph
      reduction method or an open structure rhinoplasty.

PMID- 29319788
TI  - Relationship of loop diuretic use with exercise intolerance in heart failure with
      preserved ejection fraction.

PMID- 29319790
TI  - The Preservation Rhinoplasty: A New Rhinoplasty Revolution.

PMID- 29319789
TI  - Parent-targeted home-based interventions for increasing fruit and vegetable
      intake in children: a systematic review and meta-analysis.
AB  - Context: Parent interventions delivered in the home represent a valuable approach
      to improving children's diets. Objective: This review aims to examine the
      effectiveness of parent-targeted in-home interventions in increasing fruit and
      vegetable intake in children. Data Sources: Five electronic databases were
      searched: MEDLINE, Embase, PubMed, CINAHL, and PsycINFO. Study Selection:
      Randomized and nonrandomized trials conducted in children aged 2 to 12 years and
      published in English from 2000 to 2016 were eligible. Data Extraction: Eighteen
      publications were reviewed, and 12 randomized trials were analyzed. Studies were
      pooled on the basis of outcome measure and type of intervention, resulting in 3
      separate meta-analyses. Results: Nutrition education interventions resulted in a
      small but significant increase in fruit intake (Hedges' g = 0.112; P = 0.028).
      Taste exposure interventions led to a significant increase in vegetable intake,
      with a moderate effect (Hedges' g = 0.438; P < 0.001). Interventions involving
      daily or weekly sessions reported positive outcomes more frequently than those
      using monthly sessions. Conclusions: Future interventions should incorporate
      regular taste exposure to maximize increases in vegetable intake in children.
      This is particularly important because fewer children meet national
      recommendations for vegetable intake than for fruit intake.

PMID- 29319791
TI  - Doxycycline photosensitivity.

PMID- 29319793
TI  - Facing Fears; If Medication Runs Out.

PMID- 29319792
TI  - Oncogenic osteomalacia.

PMID- 29319794
TI  - An observational analysis of insulinoma from a single institution.
AB  - Background: Insulinoma is the commonest functioning pancreatic neuroendocrine
      tumor causing hyperinsulinemic hypoglycemia. Aim: This study is aimed to evaluate
      the clinical features, preoperative laboratory and imaging diagnosis and
      pathologic findings of insulinoma. Methods: Data of the patients from 2001 to
      2016 diagnosed as insulinoma in Tongji Hospital, China were retrospectively
      extracted and analyzed. Results: A total of 40 patients were diagnosed as
      insulinoma with a male/female ratio of 0.68:1. The median onset age was 46.5
      years. Nearly all the included patients presented neurological symptoms and 60%
      presented autonomic symptoms. More than 95% of the patients met the functional
      European Neuroendocrine Tumor Society criteria including glucose, insulin and C
      peptide levels. The preoperative detection rates of ultrasonography, enhanced
      computed tomography, magnetic resonance imaging, and endoscopic ultrasonography
      were 60.50%, 84.95%, 80% and 83.3% respectively. The joint imaging examinations
      can markedly increase the detection rate. The mean tumor size was 1.89 +/- 0.72
      cm. Ki-67 index by histopathological diagnosis were all less than 20%. The
      positive rates of insulin, synaptophysin and chromogranin A were close to 100%.
      Conclusion: Laboratory tests of glucose, insulin and C-peptide are reliable for
      preoperative diagnosis. Combination of the imaging examinations can improve the
      diagnosis.

PMID- 29319795
TI  - N-Acetyl-2-Aminofluorene (AAF) Processing in Adult Rat Hepatocytes in Primary
      Culture Occurs by High-Affinity Low-Velocity and Low-Affinity High-Velocity AAF
      Metabolite-Forming Systems.
AB  - N-acetyl-2-aminofluorene (AAF) is a procarcinogen used widely in physiological
      investigations of chemical hepatocarcinogenesis. Its metabolic pathways have been
      described extensively, yet little is known about its biochemical processing,
      growth cycle expression, and pharmacological properties inside living hepatocytes
      the principal cellular targets of this hepatocarcinogen. In this report, primary
      monolayer adult rat hepatocyte cultures and high specific-activity [ring G-3 H]-N
      acetyl-2-aminofluorene were used to extend previous observations of metabolic
      activation of AAF by highly differentiated, proliferation-competent hepatocytes
      in long-term cultures. AAF metabolism proceeded by zero-order kinetics.
      Hepatocytes processed significant amounts of procarcinogen (~12 MUg AAF/106
      cells/day). Five ring-hydroxylated and one deacetylated species of AAF were
      secreted into the culture media. Extracellular metabolite levels varied during
      the growth cycle (days 0-13), but their rank quantitative order was time
      invariant: 5-OH-AAF > 7-OH-AAF > 3-OH-AAF > N-OH-AAF > aminofluorene (AF) > 1-OH
      AAF. Lineweaver-Burk analyses revealed two principal classes of metabolism:
      System I (high-affinity and low-velocity), Km[APPARENT] = 1.64 * 10-7  M and
      VMAX[APPARENT] = 0.1 nmol/106 cells/day and System II (low-affinity and high
      velocity), Km[APPARENT] = 3.25 * 10-5  M and VMAX[APPARENT] = 1000 nmol/106
      cells/day. A third system of metabolism of AAF to AF, with Km[APPARENT] and
      VMAX[APPARENT] constants of 9.6 * 10-5  M and 4.7 nmol/106 cells/day, was also
      observed. Evidence provided in this report and its companion paper suggests
      selective roles and intracellular locations for System I- and System II-mediated
      AAF metabolite formation during hepatocarcinogenesis, although some of the
      molecules and mechanisms responsible for multi-system processing remain to be
      fully defined.

PMID- 29319796
TI  - The focus in the diagnostic workup of miliary pulmonary shadowing.

PMID- 29319797
TI  - An In Silico Comparison of Protocols for Dated Phylogenomics.
AB  - In the age of genome-scale DNA sequencing, choice of molecular marker arguably
      remains an important decision in planning a phylogenetic study. Using published
      genomes from 23 primate species, we make a standardized comparison of four of the
      most frequently used protocols in phylogenomics, viz., targeted sequence
      enrichment using ultraconserved element and exon-capture probes, and restriction
      site-associated DNA sequencing (RADseq and ddRADseq). Here, we present a
      procedure to perform in silico extractions from genomes and create directly
      comparable data sets for each class of marker. We then compare these data sets in
      terms of both phylogenetic resolution and ability to consistently and precisely
      estimate clade ages using fossil-calibrated molecular-clock models. Furthermore,
      we were also able to directly compare these results to previously published data
      sets from Sanger-sequenced nuclear exons and mitochondrial genomes under the same
      analytical conditions. Our results show-although with the exception of the
      mitochondrial genome data set and the smallest ddRADseq data set-that for
      uncontroversial nodes all data classes performed equally well, that is they
      recovered the same well supported topology. However, for one difficult-to-resolve
      node comprising a rapid diversification, we report well supported but conflicting
      topologies among the marker classes consistent with the mismodeling of gene tree
      heterogeneity as demonstrated by species tree analyses of single nucleotide
      polymorphisms. Likewise, clade age estimates showed consistent discrepancies
      between data sets under strict and relaxed clock models; for recent nodes, clade
      ages estimated by nuclear exon data sets were younger than those of the UCE,
      RADseq and mitochondrial data, but vice versa for the deepest nodes in the
      primate phylogeny. This observation is explained by temporal differences in
      phylogenetic informativeness (PI), with the data sets with strong PI peaks toward
      the present underestimating the deepest node ages. Finally, we conclude by
      emphasizing that while huge numbers of loci are probably not required for
      uncontroversial phylogenetic questions-for which practical considerations such as
      ease of data generation, sharing, and aggregating, therefore become increasingly
      important-accurately modeling heterogeneous data remains as relevant as ever for
      the more recalcitrant problems.

PMID- 29319798
TI  - Volunteering Among Older Adults: Life Course Correlates and Consequences.

PMID- 29319799
TI  - Facilitating circular permutation using Restriction Free (RF) cloning.
AB  - Circular permutation is a powerful tool to test the role of topology in protein
      folding and function. Previous methods for generating circular permutants were
      based on rearranging gene elements using restriction enzymes-based cloning. Here,
      we present a Restriction Free (RF) approach to achieve circular permutation which
      is faster and more cost-effective.

PMID- 29319800
TI  - Characterization of a novel endo-type alginate lyase derived from Shewanella sp.
      YH1.
AB  - Alginate, which is an anionic polysaccharide, is widely distributed in the cell
      wall of brown algae. Alginate and the products of its degradation
      (oligosaccharides) are used in stabilizers, thickeners and gelling agents,
      especially in the food industry. The degradation of alginate generally involves a
      combination of several alginate lyases (exo-type, endo-type and oligoalginate
      lyase). Enhancing the efficiency of the production of alginate degradation
      products may require the identification of novel alginate lyases with unique
      characteristics. In this study, we isolated an alginate-utilizing bacterium,
      Shewanella sp. YH1, from seawater collected off the coast of Tottori prefecture,
      Japan. The detected novel alginate lyase was named AlgSI-PL7, and was classified
      in polysaccharide lyase family 7. The enzyme was purified from Shewanella sp. YH1
      and a recombinant AlgSI-PL7 was produced in Escherichia coli. The optimal
      temperature and pH for enzyme activity were around 45 degrees C and 8,
      respectively. Interestingly, we observed that AlgSI-PL7 was not thermotolerant,
      but could refold to its active form following an almost complete denaturation at
      approximately 60 degrees C. Moreover, the degradation of alginate by AlgSI-PL7
      produced two to five oligosaccharides, implying this enzyme was an endo-type
      lyase. Our findings suggest that AlgSI-PL7 may be useful as an industrial enzyme.

PMID- 29319801
TI  - Not So Golden After All: The Complexities of Chronic Low Back Pain in Older
      Adulthood.
AB  - Background and Objectives: The study objective was to understand how Chronic low
      back pain (CLBP) impacts key aging concepts such as retirement, housing, health,
      and independence. Research Design and Methods: Twenty-one pain clinic patients
      (66-83 years old) with CLBP engaged in 23 in-depth semistructured interviews,
      which were audio-recorded and transcribed verbatim. Guided by van Manen's
      phenomenological method, researchers used line-by-line thematic coding to analyze
      data through an iterative process. Results: Participants' accounts illustrate the
      interplay between aging and living with CLBP. Under the larger theme "Not so
      golden after all," results are reflected in five subthemes: (a) Falling apart;
      (b) Pain stigmatizes aging; (c) Hurting slowly, aging quickly; (d) Pain threatens
      independence; (e) The reality of unrealized futures. Discussion and Implications:
      This study improves our understanding of how CLBP complicates growing older with
      regard to tarnished retirements and stigmatization. Findings highlight the
      importance of coordinated care and recognition of pain-related loss.

PMID- 29319802
TI  - Functional analysis of arginine decarboxylase gene speA of Bacteroides dorei by
      markerless gene deletion.
AB  - Polyamine concentrations in the intestine are regulated by their biosynthesis by
      hundreds of gut microbial species and these polyamines are involved in host
      health and disease. However, polyamine biosynthesis has not been sufficiently
      analyzed in major members of the human gut microbiota, possibly owing to a lack
      of gene manipulation systems. In this study, we successfully performed markerless
      gene deletion in Bacteroides dorei, one of the major members of the human gut
      microbiota. The combination of a thymidine kinase gene (tdk) deletion mutant and
      a counter-selection marker tdk, which has been applied in other Bacteroides
      species, was used for the markerless gene deletion. Deletion of tdk in B. dorei
      caused 5-fluoro-2?-deoxyuridine resistance, suggesting the utility of B. dorei
      Deltatdk as the host for future markerless gene deletions. Compared to parental
      strains, an arginine decarboxylase gene (speA) deletion mutant generated in this
      system showed a severe growth defect and decreased concentration of spermidine in
      the cells and culture supernatant. Collectively, our results indicate the
      accessibility of gene deletion and the important role of speA in polyamine
      biosynthesis in B. dorei.

PMID- 29319803
TI  - Down-regulation of glutamate release from hippocampal neurons by sialidase.
AB  - Sialidase, which removes sialic acid residues in sialylglycoconjugates, is
      essential for hippocampal memory and synaptic plasticity. Enzyme activity of
      sialidase is rapidly increased in response to neural excitation. Because sialic
      acid bound to gangliosides such as the tetra-sialoganglioside GQ1b is crucial for
      calcium signalling and neurotransmitter release, neural activity-dependent
      removal of sialic acid may affect hippocampal neurotransmission. In the present
      study, we found that 2-deoxy-2, 3-didehydro-D-N-acetylneuraminic acid (DANA), a
      sialidase inhibitor, increased expression of ganglioside GQ1b/GT1a in hippocampal
      acute slices. Extracellular glutamate level in the rat hippocampus measured by
      using in vivo microdialysis was increased by the sialidase inhibitor 2, 3-dehydro
      2-deoxy-N-glycolylneuraminic acid as well as DANA. Synaptic vesicle exocytosis
      and intracellular Ca2+ increase evoked by high-K+ were also enhanced by DANA in
      primary cultured hippocampal neurons. Expression of GQ1b/GT1a was rapidly
      decreased by depolarization with high-K+, suggesting that the increase in
      sialidase activity by neural excitation is sufficient for cleavage of sialic
      acid. Our findings indicate that sialidase down-regulates glutamate release from
      hippocampal neurons via Ca2+ signalling modulation. Neural activity-dependent
      desialylation by sialidase may be a negative-feedback factor against presynaptic
      activity.

PMID- 29319804
TI  - Effects of Agricultural Organic Dusts on Human Lung-Resident Mesenchymal Stem
      (Stromal) Cell Function.
AB  - Agricultural organic dust exposures trigger harmful airway inflammation, and
      workers experiencing repetitive dust exposures are at increased risk for lung
      disease. Mesenchymal stem/stromal cells (MSCs) regulate wound repair processes in
      the lung, and may contribute to either proresolution or -fibrotic lung responses.
      It is unknown how organic dust exposures alter lung-resident MSC activation and
      proinflammatory versus prorepair programs in the lung. To address this gap in
      knowledge, we isolated human lung-resident MSC from lung tissue. Cells were
      stimulated with aqueous extracts of organic dusts (DE) derived from swine
      confinement facilities and were assessed for changes in proliferative and
      migratory capacities, and production of proinflammatory and prorepair mediators.
      Through these investigations, we found that DE induces significant release of
      proinflammatory mediators TNF-alpha, IL-6, IL-8, and matrix metalloproteases,
      while also inducing the production of prorepair mediators amphiregulin, FGF-10,
      and resolvin D1. In addition, DE significantly reduced the growth and migratory
      capacities of lung-resident MSC. Together, these investigations indicate lung
      resident MSC activation and wound repair activities are altered by organic dust
      exposures. These findings warrant future investigations to assess how organic
      dusts affect lung-resident mesenchymal stem/stromal cell function and impact
      airway inflammation, injury, and repair during agricultural aerosol exposures.

PMID- 29319805
TI  - The captive brain: torture and the neuroscience of humane interrogation.
AB  - Despite it being abhorrent and illegal, torture is sometimes employed for
      information gathering. However, the extreme stressors employed during torture
      force the brain away from the relatively narrow, adaptive range of function it
      operates within. Torture degrades signal-to-noise ratios of information yield and
      increases false positive discovery rates. As a discovery methodology, torture
      fails basic tests of veridical, reliable and replicable information discovery.
      Torture fails during interrogation because it is an assault on our core
      integrated, social, psychological and neural functioning. There is a need for a
      profound cultural shift regarding torture, recognizing that torture impairs,
      rather than facilitates, investigations and truth-finding. Rising to this
      challenge will increase operational effectiveness, eliminate prisoner abuse and
      torment, and aid veridical and actionable information gathering. Policy regarding
      prisoner and detainee interrogation need to be refocused as a behavioural and
      brain sciences problem, and not simply treated as a legal, ethical or
      philosophical problem. Getting the science, ethics and practice in line is a
      challenge, but it can and should be done.

PMID- 29319807
TI  - Crystal structure of an aldehyde oxidase from Methylobacillus sp. KY4400.
AB  - Hetero-trimeric aldehyde oxidases of bacterial origin, which use O2 to catalyse
      the oxidation of various aldehydes but not those of aromatic N-heterocycles,
      belong to the xanthine oxidase family. In the present study, the crystal
      structure of a recombinant aldehyde oxidase from Methylobacillus sp. KY4400 (Mb
      AOX) was determined at 2.5 A resolution. The structures of its subunits resemble
      those of the corresponding subunits or domains of other structurally
      characterised enzymes belonging to the family, and include a [4Fe-4 S] cluster in
      the medium subunit like that found in Escherichia coli periplasmic aldehyde
      oxidoreductase (EP-AOR). A funnel leading to the si-face of the isoalloxazine
      ring of FAD, which is narrower than those in mouse liver AOX3 and human AOX1, is
      also present and it is even narrower than that in EP-AOR. The environment
      surrounding the ring in Mb-AOX and EP-AOR is subtly different, which might
      account for their different abilities to use O2. A remarkable characteristic of
      the Mo catalytic centre in Mb-AOX is a tryptophan situated near the centre
      instead of the alanine present in other xanthine oxidase family members. The
      tryptophan residue together with other residue differences might play an
      important role in binding to aldehydes such as n-heptylaldehyde in Mb-AOX.

PMID- 29319808
TI  - Intracellular reduction of coenzyme Q homologues with a short isoprenoid side
      chain induces apoptosis of HeLa cells.
AB  - Coenzyme Q (CoQ) is an essential factor of the mitochondrial respiratory chain.
      CoQ homologues with different lengths of the isoprenoid side chain are widely
      distributed in nature, but little is known about the relationship between the
      isoprenoid side chain length and biological function; therefore, we examined the
      effects of CoQ homologues on HeLa cells. When CoQ homologues with a shorter
      isoprenoid side chain than CoQ4 were added to HeLa cells, they induced cell
      death, and the order of cytotoxic intensity was as follows: CoQ0 ? CoQ3 ~ CoQ1 >
      CoQ2 ? CoQ4. Furthermore, we found that CoQ1, CoQ2 and CoQ3 could induce caspase
      mediated apoptosis, and the order of intensity was as follows: CoQ3 > CoQ2 >=
      CoQ1. We could not identify the participation of reactive oxygen species in the
      apoptosis induction, but observed that an NAD(P)H dehydrogenase (quinone) 1
      (NQO1) inhibitor, dicumarol, could inhibit not only the intracellular reduction
      of the homologues but also apoptosis. However, because dicumarol did not affect
      well-known apoptosis inducers, such as anti-Fas IgG, tumor necrosis factor (TNF)
      alpha, TNF-related apoptosis-inducing ligand, UV-B and H2O2 of HeLa cells at all,
      we concluded that NQO1-related intracellular reduction of CoQ, or its reduced
      product, ubiquinol, may participate in the apoptosis induction of HeLa cells.

PMID- 29319806
TI  - Comparative Genomics Highlights Symbiotic Capacities and High Metabolic
      Flexibility of the Marine Genus Pseudovibrio.
AB  - Pseudovibrio is a marine bacterial genus members of which are predominantly
      isolated from sessile marine animals, and particularly sponges. It has been
      hypothesized that Pseudovibrio spp. form mutualistic relationships with their
      hosts. Here, we studied Pseudovibrio phylogeny and genetic adaptations that may
      play a role in host colonization by comparative genomics of 31 Pseudovibrio
      strains, including 25 sponge isolates. All genomes were highly similar in terms
      of encoded core metabolic pathways, albeit with substantial differences in
      overall gene content. Based on gene composition, Pseudovibrio spp. clustered by
      geographic region, indicating geographic speciation. Furthermore, the fact that
      isolates from the Mediterranean Sea clustered by sponge species suggested host
      specific adaptation or colonization. Genome analyses suggest that Pseudovibrio
      hongkongensis UST20140214-015BT is only distantly related to other Pseudovibrio
      spp., thereby challenging its status as typical Pseudovibrio member. All
      Pseudovibrio genomes were found to encode numerous proteins with SEL1 and
      tetratricopeptide repeats, which have been suggested to play a role in host
      colonization. For evasion of the host immune system, Pseudovibrio spp. may depend
      on type III, IV, and VI secretion systems that can inject effector molecules into
      eukaryotic cells. Furthermore, Pseudovibrio genomes carry on average seven
      secondary metabolite biosynthesis clusters, reinforcing the role of Pseudovibrio
      spp. as potential producers of novel bioactive compounds. Tropodithietic acid,
      bacteriocin, and terpene biosynthesis clusters were highly conserved within the
      genus, suggesting an essential role in survival, for example through growth
      inhibition of bacterial competitors. Taken together, these results support the
      hypothesis that Pseudovibrio spp. have mutualistic relations with sponges.

PMID- 29319809
TI  - Increased Microglial CSF1R Expression in the SIV/Macaque Model of HIV CNS
      Disease.
AB  - Chronic microglial activation and associated neuroinflammation are key factors in
      neurodegenerative diseases including HIV-associated neurocognitive disorders.
      Colony stimulating factor 1 receptor (CSF1R)-mediated signaling is constitutive
      in cells of the myeloid lineage, including microglia, promoting cell survival,
      proliferation, and differentiation. In amyotrophic lateral sclerosis and
      Alzheimers disease, CSF1R is upregulated. Inhibiting CSF1R signaling in animal
      models of these diseases improved disease outcomes. In our studies, CNS
      expression of the CSF1R ligand, colony-stimulating factor 1 (CSF1) was
      significantly increased in a SIV/macaque model of HIV CNS disease. Using a
      Nanostring nCounter immune panel, we found CSF1 overexpression was strongly
      correlated with upregulation of microglial genes involved in antiviral and
      oxidative stress responses. Using in situ hybridization, we found that CSF1R mRNA
      was only present in Iba-1 positive microglia. By ELISA and immunostaining with
      digital image analysis, SIV-infected macaques had significantly higher CSF1R
      levels in frontal cortex than uninfected macaques (p = 0.018 and p = 0.02,
      respectively). SIV-infected macaques treated with suppressive ART also had
      persistently elevated CSF1R similar to untreated SIV-infected macaques.
      Coordinate upregulation of CSF1 and CSF1R expression implicates this signaling
      pathway in progressive HIV CNS disease.

PMID- 29319810
TI  - The Second Phase of Insulin Secretion in Nondiabetic Islet-Grafted Recipients Is
      Altered and Can Predict Graft Outcome.
AB  - Context: Islet transplantation (IT) can treat patients with severely unstable
      type 1 diabetes. Prehepatic kinetics of insulin secretion (ISec) in two phases
      can be calculated by C-peptide levels during meal tests. We proposed to describe
      the ISec profile after a mixed-meal tolerance test (MMTT) in IT recipients and to
      determine whether the calculated ISec indexes can predict graft outcome. Methods:
      We analyzed 34 MMTT among 11 patients who underwent IT between 2011 and 2016 and
      compared them with healthy controls and patients with type 2 diabetes (T2D). ISec
      indexes and insulin sensitivity were calculated from models of Van Cauter, Breda,
      and Mari after MMTT. Graft success was defined by total insulin independence
      without any criteria for diabetes. Results: In patients with successful IT, the
      first- and second-phase ISec indexes were lower than those of controls (P <
      0.001) and did not differ from those of the T2D group. Nevertheless, insulin
      sensitivity of IT recipients was similar to that of the control group and higher
      than that of the T2D group. The index of the second phase of ISec phiS was
      correlated with total infused islet equivalents (IEQs), was a good predictor of
      diabetes (re)occurrence, and allowed us to calculate 9500 IEQ/kg as the minimum
      needed to reach insulin independence. Conclusion: We showed that indexes from the
      first and second phases of ISec are altered in insulin-independent IT recipients.
      Higher sensitivity distinguishes them from patients with T2D. Even in insulin
      independent patients, IT remains a marginal mass model. Moreover, phiS can
      estimate transplanted islet mass and predict IT recipient outcomes.

PMID- 29319811
TI  - Identification of a consensus motif in Erg28p required for C-4 demethylation in
      yeast ergosterol biosynthesis based on mutation analysis.
AB  - The Erg28p protein is localized to the endoplasmic reticulum, where it acts as a
      scaffold to tether the C-4 demethylase complex involved in the sterol
      biosynthesis pathway of Saccharomyces cerevisiae. However, due to the challenges
      involved in characterizing the interactions of membrane proteins, the precise
      region of Erg28p that is responsible for the assembly of this enzyme complex
      remains unknown. To address this question, mutants with serial truncations in the
      C-terminus of Erg28p were constructed based on a topology prediction of its
      transmembrane domain. Sterol profiles demonstrated that intermediates involved in
      the stepwise removal of the two C-4 methyl groups from the tetracyclic sterol
      ring were accumulated in the ERG28Delta135-447 strain. Homologous alignment of
      Erg28p further identified a highly conserved 10-amino acid sequence
      (63LS/QARTFGT/LWT72) within the truncated region of ERG28Delta136-273.
      Complementation of the BY4741/erg28 strain with the ScERG28Delta175-204 plasmid
      resulted both in a significant growth inhibition and a reduction of ergosterol
      biosynthesis compared with the plasmid without the Delta175-204 truncation.
      Furthermore, homology modeling of the Erg28p mutant indicated that the deletion
      of residues 63-72 significantly disrupted the 3D structure of the four parallel
      helices in Erg28p. Taken together, the data indicate that the region spanning
      amino acids 63-72 constitutes a key consensus motif within Erg28p that is
      required for sterol C-4 demethylation during ergosterol biosynthesis in S.
      cerevisiae.

PMID- 29319812
TI  - Deuterostome Genomics: Lineage-Specific Protein Expansions That Enabled Chordate
      Muscle Evolution.
AB  - Fish-like larvae were foundational to the chordate body plan, given the basal
      placement of free-living lancelets. That body plan probably made it possible for
      chordate ancestors to swim by beating a tail formed of notochord and bilateral
      paraxial muscles. In order to investigate the molecular genetic basis of the
      origin and evolution of paraxial muscle, we deduced the evolutionary histories of
      16 contractile protein genes from paraxial muscle, based on genomic data from all
      five deuterostome lineages, using a newly developed orthology identification
      pipeline and a species tree. As a result, we found that more than twice as many
      orthologs of paraxial muscle genes are present in chordates, as in nonchordate
      deuterostomes (ambulacrarians). Orthologs of paraxial-type actin and troponin C
      genes are absent in ambulacrarians and most paraxial muscle protein isoforms
      diversified via gene duplications that occurred in each chordate lineage.
      Analyses of genes with known expression sites indicated that some isoforms were
      reutilized in specific muscles of nonvertebrate chordates via gene duplications.
      As orthologs of most paraxial muscle genes were present in ambulacrarians, in
      addition to expression patterns of related genes and functions of the two protein
      isoforms, regulatory mechanisms of muscle genes should also be considered in
      future studies of the origin of paraxial muscle.

PMID- 29319813
TI  - Testing the Implementation of the Veder Contact Method: A Theatre-Based
      Communication method in Dementia Care.
AB  - Background and Objectives: There is a lack of research on implementation of
      person-centered care in nursing home care. The purpose of this study was to
      assess the implementation of the Veder contact method (VCM), a new person
      centered method using theatrical, poetic and musical communication for
      application in 24-hr care. Research Design and Methods: Caregivers (n = 136) and
      residents (n = 141) participated in a 1-year quasi-experimental study. Foundation
      Theater Veder implemented VCM on six experimental wards and rated implementation
      quality. Six control wards delivered care-as-usual. Before and after
      implementation, caregiver behavior was assessed during observations using the
      Veder-observation list and Quality of Caregivers' Behavior-list. Caregiver
      attitude was rated with the Approaches to Dementia Questionnaire. Quality of
      life, behavior, and mood of the residents were measured with QUALIDEM, INTERACT
      and FACE. Residents' care plans were examined for person-centered background
      information. Results: Significant improvements in caregivers' communicative
      behavior (i.e., the ability to apply VCM, establishing positive interactions) and
      some aspects of residents' behavior and quality of life (i.e., positive affect,
      social relations) were found on the experimental wards with a high implementation
      score, as compared to the experimental wards with a low implementation score, and
      the control wards. No significant differences were found between the groups in
      caregivers' attitudes, residents' care plans, or mood. Discussion and
      Implications: The positive changes in caregivers' behavior and residents' well
      being on the high implementation score wards confirm the partly successful VCM
      implementation. Distinguishing between wards with a high and low implementation
      score provided insight into factors which are crucial for successful
      implementation.

PMID- 29319814
TI  - Single- versus multiple-sample method to measure glomerular filtration rate.
AB  - Background: There are many different ways to measure glomerular filtration rate
      (GFR) using various exogenous filtration markers, each having their own strengths
      and limitations. However, not only the marker, but also the methodology may vary
      in many ways, including the use of urinary or plasma clearance, and, in the case
      of plasma clearance, the number of time points used to calculate the area under
      the concentration-time curve, ranging from only one (Jacobsson method) to eight
      (or more) blood samples. Methods: We collected the results obtained from 5106
      plasma clearances (iohexol or 51Cr-ethylenediaminetetraacetic acid (EDTA)) using
      three to four time points, allowing GFR calculation using the slope-intercept
      method and the Brochner-Mortensen correction. For each time point, the Jacobsson
      formula was applied to obtain the single-sample GFR. We used Bland-Altman plots
      to determine the accuracy of the Jacobsson method at each time point. Results:
      The single-sample method showed within 10% concordances with the multiple-sample
      method of 66.4%, 83.6%, 91.4% and 96.0% at the time points 120, 180, 240 and
      >=300 min, respectively. Concordance was poorer at lower GFR levels, and this
      trend is in parallel with increasing age. Results were similar in males and
      females. Some discordance was found in the obese subjects. Conclusion: Single
      sample GFR is highly concordant with a multiple-sample strategy, except in the
      low GFR range (<30 mL/min).

PMID- 29319815
TI  - Chemical Analysis and Simulated Pyrolysis of Tobacco Heating System 2.2 Compared
      to Conventional Cigarettes.
AB  - Introduction: Tobacco Heating System 2.2 (THS 2.2, marketed as iQOS), is a heat
      not-burn (HNB) tobacco product that has been successfully introduced to global
      markets. Despite its expanding market, few independent and systematic researches
      into THS 2.2 have been carried out to date. Methods: We tested a comprehensive
      list of total particulate matter (TPM), water, tar, nicotine, propylene glycol,
      glycerin, carbon monoxide, volatile organic compounds, aromatic amines, hydrogen
      cyanide, ammonia, N-nitrosamines, phenol, and polycyclic aromatic hydrocarbon
      under both ISO and HCI regimes. We also simulated pyrolysis of THS 2.2 heating
      sticks and made comparisons with conventional cigarette tobacco fillers using
      comprehensive gas chromatography-mass spectrometry (GC * GC-MS) to determine
      whether the specially designed ingredients help reduce harmful constituents.
      Results: Other than some carbonyls, ammonia, and N-nitrosoanabasine (NAB), the
      delivered releases from THS 2.2 were at least 80% lower than those from 3R4F. Tar
      and nicotine remained almost the same as 3R4F. Interestingly, the normalized
      yield of THS 2.2 to 3R4F under the HCI regime was lower than under the ISO
      regime. Conclusions: THS 2.2 delivered fewer harmful constituents than the
      conventional cigarette 3R4F. Simulated pyrolysis results showed that the lower
      temperature instead of specially designed ingredients contributed to the distinct
      shift. In particular, if smoking machines are involved to evaluate the HNB
      products, smoking regimes of heat-not-burn tobacco products should be carefully
      chosen. Implications: To our knowledge, few independent studies of HNB products
      have been published. In this paper, a comprehensive list of chemical releases was
      tested systematically and compared to those from 3R4F. Although THS 2.2 generates
      lower levels of harmful constituents, the nicotine and tar levels were almost
      identical to 3R4F.The results should be discussed carefully in the future when
      assess the dual-use with other conventional cigarettes, nicotine dependence of
      HNB products, etc. This study also suggests that regulatory agencies should pay
      attention to the smoking regimes that are adopted to evaluate HNB tobacco
      products.

PMID- 29319816
TI  - Author Response.

PMID- 29319817
TI  - High-Affinity Low-Capacity and Low-Affinity High-Capacity N-Acetyl-2
      Aminofluorene (AAF) Macromolecular Binding Sites Are Revealed During the Growth
      Cycle of Adult Rat Hepatocytes in Primary Culture.
AB  - Long-term cultures of primary adult rat hepatocytes were used to study the
      effects of N-acetyl-2-aminofluorene (AAF) on hepatocyte proliferation during the
      growth cycle; on the initiation of hepatocyte DNA synthesis in quiescent
      cultures; and, on hepatocyte DNA replication following the initiation of DNA
      synthesis. Scatchard analyses were used to identify the pharmacologic properties
      of radiolabeled AAF metabolite binding to hepatocyte macromolecules. Two classes
      of growth cycle-dependent AAF metabolite binding sites-a high-affinity low
      capacity site (designated Site I) and a low-affinity high-capacity site
      (designated Site II)-associated with two spatially distinct classes of
      macromolecular targets, were revealed. Based upon radiolabeled AAF metabolite
      binding to purified hepatocyte genomic DNA or to DNA, RNA, proteins, and lipids
      from isolated nuclei, Site IDAY 4 targets (KD[APPARENT] ~ 2-4*10-6 M and
      BMAX[APPARENT] ~ 6 pmol/106 cells/24 h) were consistent with genomic DNA; and
      with AAF metabolized by a nuclear cytochrome P450. Based upon radiolabeled AAF
      binding to total cellular lysates, Site IIDAY 4 targets (KD[APPARENT] ~ 1.5*10-3
      M and BMAX[APPARENT] ~ 350 pmol/106 cells/24 h) were consistent with cytoplasmic
      proteins; and with AAF metabolized by cytoplasmic cytochrome P450s. DNA synthesis
      was not inhibited by concentrations of AAF that saturated DNA binding in the
      neighborhood of the Site I KD. Instead, hepatocyte DNA synthesis inhibition
      required higher concentrations of AAF approaching the Site II KD. These
      observations raise the possibility that carcinogenic DNA adducts derived from AAF
      metabolites form below concentrations of AAF that inhibit replicative and repair
      DNA synthesis.

PMID- 29319818
TI  - A Study for the Ages.

PMID- 29319819
TI  - Development and External Validation of Risk Scores for Cardiovascular
      Hospitalization and Rehospitalization in Patients With Diabetes.
AB  - Context: Cardiovascular disease (CVD) is a common and costly reason for
      hospitalization and rehospitalization among patients with type 2 diabetes.
      Objective: This study aimed to develop and externally validate two risk
      prediction models for cardiovascular hospitalization and cardiovascular
      rehospitalization. Design: Two independent prospective cohorts. Setting: The
      derivation cohort includes 4704 patients with type 2 diabetes from 18 general
      practices in Cambridgeshire. The validation cohort comprises 1121 patients with
      type 2 diabetes from post-trial follow-up data. Main Outcome Measure:
      Cardiovascular hospitalization over 2 years and cardiovascular rehospitalization
      after 90 days of the prior CVD hospitalization. Results: The absolute rate of
      cardiovascular hospitalization and rehospitalization was 12.5% and 6.7% in the
      derivation cohort and 16.3% and 7.0% in the validation cohort. Discrimination of
      the models was similar in both cohorts, with C statistics above 0.70 and
      excellent calibration of observed and predicted risks. Conclusion: Two prediction
      models that quantify risks of cardiovascular hospitalization and
      rehospitalization have been developed and externally validated. They are based on
      a small number of clinical measurements that are available for patients with type
      2 diabetes in many developed countries in primary care settings and could serve
      as the tools to screen the population at high risk of cardiovascular
      hospitalization and rehospitalization.

PMID- 29319820
TI  - Embryo Implantation: War in Times of Love.
AB  - Contrary to widespread belief, the implantation of an embryo for the initiation
      of pregnancy is like a battle, in that the embryo uses a variety of coercive
      tactics to force its acceptance by the endometrium. We propose that embryo
      implantation involves a three-step process: (1) identification of a receptive
      endometrium; (2) superimposition of a blastocyst-derived signature onto the
      receptive endometrium before implantation; and finally (3) breaching by the
      embryo and trophoblast invasion, culminating in decidualization and placentation.
      We review here the story that is beginning to emerge, focusing primarily on the
      cells that are in "combat" during this process.

PMID- 29319821
TI  - Probiotic potency of Lactobacillus plantarum KX519413 and KX519414 isolated from
      honey bee gut.
AB  - The Indian honey bee Apis cerana indica, which harbors an abundant and diverse
      range of lactic acid bacteria (LAB) in their gut with beneficial effects, was
      used as the source for the isolation of LAB. In the present study, two LAB
      isolates from honey bee gut were selected primarily based on their phenotypic and
      selective biochemical characterization, followed by PCR and identified using 16S
      rRNA sequencing as Lactobacillus plantarum and were registered in National Centre
      for Biotechnology Information under accession number KX519413 and KX519414. The
      probiotic potency of test strains indicated their survivability at acidic pH,
      bile salts and viability in simulated gastric juice enabling them to withstand
      gastrointestinal tract conditions. Evaluation of cell surface properties
      suggested that they possess an important defense mechanism against the pathogen
      since they are hydrophobic, auto-aggregative and have co-aggregative ability.
      Further, efficient exopolysaccharide production by them indicates not only their
      ability to enrich biofilm formation and auto-aggregation, but also enhances
      bacterial adhesion and colonization on the host intestinal tract. The present
      study concluded that L. plantarum from the gut of Apis cerana indica possesses
      probiotic potency, and potential candidates for use as food besides application
      in nutraceutical and pharmaceutical industries.

PMID- 29319822
TI  - An Animal Model of Abacavir-Induced HLA-Mediated Liver Injury.
AB  - Genome-wide association studies indicate that several idiosyncratic adverse drug
      reactions are highly associated with specific human leukocyte antigen (HLA)
      alleles. For instance, abacavir, a human immunodeficiency virus reverse
      transcriptase inhibitor, induces multiorgan toxicity exclusively in patients
      carrying the HLA-B*57:01 allele. However, the underlying mechanism is unclear due
      to a lack of appropriate animal models. Previously, we developed HLA-B*57:01
      transgenic mice and found that topical application of abacavir to the ears
      induced proliferation of CD8+ lymphocytes in local lymph nodes. Here, we
      attempted to reproduce abacavir-induced liver injury in these mice. However, oral
      administration of abacavir alone to HLA-B*57:01 transgenic mice did not increase
      levels of the liver injury marker alanine aminotransferase. Considering the
      importance of innate immune activation in mouse liver, we treated mice with CpG
      oligodeoxynucleotide, a toll-like receptor 9 agonist, plus abacavir. This
      resulted in a marked increase in alanine aminotransferase, pathological changes
      in liver, increased numbers of activated CD8+ T cells, and tissue infiltration by
      immune cells exclusively in HLA-B*57:01 transgenic mice. These results indicate
      that CpG oligodeoxynucleotide-induced inflammatory reactions and/or innate immune
      activation are necessary for abacavir-induced HLA-mediated liver injury
      characterized by infiltration of CD8+ T cells. Thus, we developed the first mouse
      model of HLA-mediated abacavir-induced idiosyncratic liver injury. Further
      investigation will show that the proposed HLA-mediated liver injury model can be
      applied to other combinations of drugs and HLA types, thereby improving drug
      development and contributing to the development of personalized medicine.

PMID- 29319824
TI  - ?

PMID- 29319823
TI  - Differentially Expressed mRNA Targets of Differentially Expressed miRNAs Predict
      Changes in the TP53 Axis and Carcinogenesis-Related Pathways in Human
      Keratinocytes Chronically Exposed to Arsenic.
AB  - Arsenic is a widely distributed toxic natural element. Chronic arsenic ingestion
      causes several cancers, especially skin cancer. Arsenic-induced cancer mechanisms
      are not well defined, but several studies indicate that mutation is not the
      driving force and that microRNA expression changes play a role. Chronic low
      arsenite exposure malignantly transforms immortalized human keratinocytes
      (HaCaT), serving as a model for arsenic-induced skin carcinogenesis. Early
      changes in miRNA expression in HaCaT cells chronically exposed to arsenite will
      reveal early steps in transformation. HaCaT cells were maintained with 0/100 nM
      NaAsO2 for 3 and 7 weeks. Total RNA was purified. miRNA and mRNA expression was
      assayed using Affymetrix microarrays. Targets of differentially expressed miRNAs
      were collected from TargetScan 6.2, intersected with differentially expressed
      mRNAs using Partek Genomic Suite software, and mapped to their pathways using
      MetaCore software. MDM2, HMGB1 and TP53 mRNA, and protein levels were assayed by
      RT-qPCR and Western blot. Numerous miRNAs and mRNAs involved in carcinogenesis
      pathways in other systems were differentially expressed at 3 and 7 weeks. A TP53
      regulatory network including MDM2 and HMGB1 was predicted by the miRNA and mRNA
      networks. Total TP53 and TP53-S15-phosphorylation were induced. However, TP53
      K382-hypoacetylation suggested that the induced TP53 is inactive in arsenic
      exposed cells. Our data provide strong evidence that early changes in miRNAs and
      target mRNAs may contribute to arsenic-induced carcinogenesis.

PMID- 29319825
TI  - ?

PMID- 29319826
TI  - ?

PMID- 29319827
TI  - ?

PMID- 29319828
TI  - ?

PMID- 29319830
TI  - ?

PMID- 29319829
TI  - ?

PMID- 29319831
TI  - ?

PMID- 29319832
TI  - ?

PMID- 29319833
TI  - ?
AB  - A previously healthy 21-year old man presented to the emergency department with
      sudden onset central chest pain exacerbated by breathing. A plain chest X-ray
      showed air within the mediastinum and pericardium confirmed by a CT scan with
      contrast. The patient history did not raise suspicion of any concomitant disease
      and the diagnosis of spontaneous pneumomediastinum with pneumopericardium was
      made. The patient recovered completely over the next few days with bed rest and
      analgesics. Spontaneous pneumomediastinum is an uncommon disease caused by
      rupture of perivascular alveoli causing air leakage to the mediastinum. The
      condition is benign and self-resolving in most cases. Pneumopericardium, a rare
      complication to spontaneous pneumomediastinum, is also usually self-resolving but
      may cause cardiac tamponade requiring intervention. Spontaneous pneumomediastinum
      must be differentiated from secondary pneumomediastinum caused by an underlying
      condition, such as esofageal rupture, trauma or infection, which may require
      specific treatment.

PMID- 29319834
TI  - ?
AB  - Each year 6,800 bariatric operations are performed in Sweden. Bariatric surgery
      involves both a reduced intake and a reduced absorption of vitamins and minerals.
      There has been debate about whose responsibility long-term follow-up is,
      particularly regarding monitoring vitamin and mineral status. The Swedish Society
      for Bariatric Surgery and the Norwegian Association for Bariatric Surgery, who
      oversee their respective national quality registers, have appointed an expert
      group to develop guidelines for postoperative supplementation and nutritional
      monitoring of vitamins and minerals, along with a schedule for routine follow-up.
      Several existing international guidelines have served as the basis for the
      development of this guidance. The Finnish Association for Metabolic Surgery and
      The Danish Association for the Study of Obesity have also decided to adopt the
      recommendations. The care of the patient group with severe obesity is a common
      responsibility of primary care and hospitals, as patients are heavily affected by
      obesity-related morbidity, which, even without surgery, requires major health
      care efforts, not least from primary care. After surgery, a large proportion of
      these efforts can be reduced, but focus changes.

PMID- 29319835
TI  - ?
AB  - Mason performed the first gastric bypass (GBP) for obesity in 1967 after having
      observed substantial weight loss in patients operated for gastric ulcer.  The
      weight loss after GBP is 30 % and 2/3 of patients with type II diabetes can stop
      their medication. Half of the patients can stop medication for hypertension or
      hyperlipidemia, 75% are cured from reflux and obstructive sleep apnea. GBP
      prolongs survival especially among diabetics. Restriction and malabsorption is of
      minor importance for weight loss. The mechanisms underlying weight loss and
      diabetes remissions are endocrine. GBP enhances food passage to the distal small
      bowel where the food contact stimulates release of satiety hormones from
      endocrine cells. Elevated levels of these hormones cause weight loss, increases
      insulin secretion and counteracts weight induced decrease in resting metabolic
      rate, an important starving protection mechanism that activates when fasting and
      makes traditional weight loss difficult.

PMID- 29319836
TI  - ?
AB  - TB can be detected with PCR - but only in smear-positive respiratory samples
      Unnecessary and inappropriate clinical requests represent a great waste of time
      and money and may also result in false diagnoses. PCR-techniques, such as Cobas
      TaqMan MTB, are used for rapid detection of tuberculosis (TB).  These assays are
      only validated for respiratory specimens, but they are commonly requested also
      for non-respiratory specimens.  These assays perform well in smear-positive
      respiratory samples, while the sensitivities are quite unsatisfactory for both
      respiratory and non-respiratory smear-negatives samples. The specificity is high
      and it is possible to rapidly distinguish between TB and infections caused by
      environmental mycobacteria. The analyses demonstrate, furthermore, that PCR
      assays cannot be used to evaluate treatment, detect relapses or exclude TB. Nor
      can these assays be used to evaluate contagiousness or to screen for TB.

PMID- 29319837
TI  - Medicaid Credentialing Made Simple.
AB  - A new partnership by the Texas Medical Association and the Texas Association of
      Health Plans will soon streamline the process of getting credentialed - and
      recredentialed - for Medicaid health plans.

PMID- 29319838
TI  - Questions Abound.
AB  - The Texas Medical Board's new rules on inspecting clinics for failure to register
      as pain management clinics have provisions of potential concern for doctors.

PMID- 29319839
TI  - Are You Experienced?
AB  - A case going before the Texas Supreme Court spotlights the Medical Disclosure
      Panel and what physicians must disclose before performing a procedure.

PMID- 29319840
TI  - Does Texas Need More Medical Schools?
AB  - By 2020, Texas will be opening three new medical schools. Will there be enough
      residency positions for all the new students?

PMID- 29319841
TI  - Can Texas Do Death Better?
AB  - Filling out death certificates can be confusing for Texas physicians, and vital
      health information often gets left off of forms. Because of this, officials don't
      have accurate information on how Texans are dying.

PMID- 29319842
TI  - Quantitative evaluation of potential irradiation geometries for carbon-ion beam
      grid therapy.
AB  - PURPOSE: Radiotherapy using grids containing cm-wide beam elements has been
      carried out sporadically for more than a century. During the past two decades,
      preclinical research on radiotherapy with grids containing small beam elements,
      25 MUm-0.7 mm wide, has been performed. Grid therapy with larger beam elements is
      technically easier to implement, but the normal tissue tolerance to the treatment
      is decreasing. In this work, a new approach in grid therapy, based on
      irradiations with grids containing narrow carbon-ion beam elements was evaluated
      dosimetrically. The aim formulated for the suggested treatment was to obtain a
      uniform target dose combined with well-defined grids in the irradiated normal
      tissue. The gain, obtained by crossfiring the carbon-ion beam grids over a
      simulated target volume, was quantitatively evaluated. METHODS: The dose
      distributions produced by narrow rectangular carbon-ion beams in a water phantom
      were simulated with the PHITS Monte Carlo code. The beam-element height was set
      to 2.0 cm in the simulations, while the widths varied from 0.5 to 10.0 mm. A
      spread-out Bragg peak (SOBP) was then created for each beam element in the grid,
      to cover the target volume with dose in the depth direction. The dose
      distributions produced by the beam-grid irradiations were thereafter constructed
      by adding the dose profiles simulated for single beam elements. The variation of
      the valley-to-peak dose ratio (VPDR) with depth in water was thereafter
      evaluated. The separation of the beam elements inside the grids were determined
      for different irradiation geometries with a selection criterion. RESULTS: The
      simulated carbon-ion beams remained narrow down to the depths of the Bragg peaks.
      With the formulated selection criterion, a beam-element separation which was
      close to the beam-element width was found optimal for grids containing 3.0-mm
      wide beam elements, while a separation which was considerably larger than the
      beam-element width was found advantageous for grids containing 0.5-mm-wide beam
      elements. With the single-grid irradiation setup, the VPDRs were close to 1.0
      already at a distance of several cm from the target. The valley doses given to
      the normal tissue at 0.5 cm distance from the target volume could be limited to
      less than 10% of the mean target dose if a crossfiring setup with four interlaced
      grids was used. CONCLUSIONS: The dose distributions produced by grids containing
      0.5- and 3.0-mm wide beam elements had characteristics which could be useful for
      grid therapy. Grids containing mm-wide carbon-ion beam elements could be
      advantageous due to the technical ease with which these beams can be produced and
      delivered, despite the reduced threshold doses observed for early and late
      responding normal tissue for beams of millimeter width, compared to
      submillimetric beams. The treatment simulations showed that nearly homogeneous
      dose distributions could be created inside the target volumes, combined with low
      valley doses in the normal tissue located close to the target volume, if the
      carbon-ion beam grids were crossfired in an interlaced manner with optimally
      selected beam-element separations. The formulated selection criterion was found
      useful for the quantitative evaluation of the dose distributions produced by the
      different irradiation setups.

PMID- 29319843
TI  - Prediction of Vancomycin Dose for Recommended Trough Concentrations in Pediatric
      Patients With Cystic Fibrosis.
AB  - Vancomycin is a key antibiotic used in the treatment of multiple conditions
      including infections associated with cystic fibrosis and methicillin-resistant
      Staphylococcus aureus. The present study sought to develop a model based on
      empirical evidence of optimal vancomycin dose as judged by clinical observations
      that could accelerate the achievement of desired trough level in children with
      cystic fibrosis. Transformations of dose and trough were used to arrive at
      regression models with excellent fit for dose based on weight or age for a target
      trough. Results of this study indicate that the 2 proposed regression models are
      robust to changes in age or weight, suggesting that the daily dose on a per
      kilogram basis is determined primarily by the desired trough level. The results
      show that to obtain a vancomycin trough level of 20 MUg/mL, a dose of 80
      mg/kg/day is needed. This analysis should improve the efficiency of vancomycin
      usage by reducing the number of titration steps, resulting in improved patient
      outcome and experience.

PMID- 29319844
TI  - Gender differences in intimate-conflict initiation and escalation tendencies.
AB  - According to gender motivation theory, men are driven by a desire to enhance
      their status; whereas, women are motivated by a desire to reduce risk, and the
      behavioral expressions of those motivations are context-dependent. In order to
      test this theory in the context of intimate relationships, this study compared
      men's and women's escalatory tendencies in the initial development of intimate
      conflict. These tendencies were conceptualized in terms of four attributes: two
      attributes that represent response intention (decision and style) and two others
      that represent motivations for that intention (putting one's partner in his or
      her place and avoiding conflict). These attributes were measured in the context
      of five hypothetical situations. Each of those scenarios involved potential
      escalation of intimate conflict, following an intimate partner's aggressive
      verbal demand. The study involved a convenience sample of 403 male and female
      participants. The findings show that, in the initial steps of intimate-conflict
      development, women tend toward escalation more than men. The findings also show
      that the escalatory tendency, as conceptualized and measured using the examined
      scenarios, corresponds to actual behavior exhibited in the resolution of common
      issues in the couples' lives. These findings reinforce gender motivation theory.

PMID- 29319845
TI  - IL-37 inhibits IL-4/IL-13-induced CCL11 production and lung eosinophilia in
      murine allergic asthma.
AB  - BACKGROUND: IL-37 is emerging as an anti-inflammatory cytokine, particularly in
      innate inflammation. However, the role of IL-37 in Th2-mediated allergic lung
      inflammation remains uncertain. We sought to determine the role and the
      underlying mechanisms of IL-37 in the development of house dust mites (HDM)
      induced murine asthma model. METHODS: We examined the effect of IL-37
      administration during the sensitization or challenge phase on Th2-mediated
      allergic asthma induced by inhaled HDM. Cellular source of CCL11 and distribution
      of IL-37 receptors, IL-18Ralpha and IL-1R8, were determined in HDM-exposed lungs.
      Finally, we examined the effect of IL-37 on CCL11 production and STAT6 activation
      in different primary lung structural cell types upon IL-4/IL-13 stimulation.
      RESULTS: IL-37 had no effect on HDM sensitization, but when administrated during
      the challenge phase, significantly attenuated pulmonary eosinophilia, CCL11
      production, and airway hyper-reactivity (AHR). Interestingly, IL-37 treatment had
      no significant effects on lung infiltrating T cells and Th2 cytokine production.
      Intranasal co-administration of CCL11 reversed the inhibiting effect of IL-37 on
      HDM-induced pulmonary eosinophilia and AHR. Furthermore, we demonstrated that
      CCL11 was primarily expressed by fibroblasts and airway smooth muscle cells
      (AMSC), while IL-37 receptors by tracheobronchial epithelial cells (TEC). In
      vitro study showed that IL-37 inhibited IL-4/IL-13-induced STAT6 activation and
      CCL11 production by fibroblasts and AMSC, which was dependent on its direct
      action on TEC. Moreover, cell contact was required for the inhibitory effect of
      IL-37-treated TEC. CONCLUSIONS: IL-37 attenuates HDM-induced asthma, possibly by
      inhibiting IL-4/IL-13-induced CCL11 production by fibroblasts and AMSC via its
      direct act on TEC.

PMID- 29319846
TI  - Phototoxic drug reaction with the novel agent rovalpituzumab tesirine.

PMID- 29319848
TI  - The Management of Closed Liver Trauma Treated by Hemihepatectomy.
AB  - A case of closed liver trauma treated by hemihepatectomy is described, and the
      management of the metabolic derangements following this operation are discussed.

PMID- 29319847
TI  - Decision making in breast cancer risk reduction.

PMID- 29319849
TI  - The Use of Surgery and Local Temperature Elevation in Mycobacterium Ulcerans
      Infection.
AB  - Six cases of Mycobacterium infection are described. A critical evaluation of the
      various methods of treatment used is presented. The conclusions are that drugs
      have no place in the primary treatment of the condition, and that wide surgical
      excision and partial, thickness skin grafting followed by the application of heat
      by means of a specially constructed heat cradle are the best form of treatment.
      Problems associated with surgical management are discussed.

PMID- 29319850
TI  - The Use of Scalp Flaps Following Resection of Oral Cancer1.
AB  - This paper describes the use of scalp flaps to provide cover in the defects left
      after resections for oral cancer. Scalp flaps provide cover and forehead flaps
      provide lining. Combined scalp and forehead flaps have been carried on
      subcutaneous vascular pedicles and on carrier skin segments. These have been used
      even after ligation of the external carotid artery. They have also been brought
      down like a visor on bilateral subcutaneous vascular pedicles.

PMID- 29319851
TI  - The Effect of Surgery, Injury, and Prolonged Bed Rest on Calf Blood Flow.
AB  - Using strain gauge plethysmography, the resting calf blood flow, mainly a measure
      of muscle blood flow, has been estimated in control subjects, in patients during
      and after surgical procedures, and in patients during prolonged bed rest
      following surgery or operation. During general surgical procedures, the calf
      blood flow was reduced by 38% of the preoperative values. After operation, there
      was a progressive fall in calf blood flow, the lowest values showing a reduction
      averaging 58% of the preoperative flow. The reductions in blood flow were
      associated with an increase in peripheral resistance, indicating that local
      vasoconstriction was the cause of the reduced flow. Low calf blood flow was also
      shown to occur in patients who were confined to bed for long periods after injury
      or operation. It is suggested that by reducing venous return, the decreased calf
      blood flow during and after surgery, and during prolonged bed rest, may be a
      factor in the development of deep vein thrombosis in. surgical patients.

PMID- 29319852
TI  - Pseudocyst of the Pancreas.
AB  - A review is presented of cases of pseudocyst of the pancreas occurring over a 10
      year period at the Alfred Hospital, Melbourne. There were 14 cases. The clinical
      presentation, surgical management and biochemical characteristics of these cysts
      arc described and discussed.

PMID- 29319853
TI  - Acute Primary Inversion of the Caecum.
AB  - A case of acute primary inversion of the caecum is presented. The importance of
      early operation is stressed. The importance of the condition in the differential
      diagnosis of appendicitis is mentioned.

PMID- 29319855
TI  - The Early History of the Formation of the Faculty of Anaesthetists: Some
      Recollections.

PMID- 29319854
TI  - Anterior Tibial Syndrome following Restoration of Arterial Flow.
AB  - Sudden revascularization of an ischemic limb may be followed by the onset of the
      anterior tibial syndrome. Five cases are reported in which this syndrome occurred
      following successful revascularization, four of them requiring fasciotomy. The
      "reopening syndrome" may on rare occasions follow revascularization, and the
      causes and treatment of this phenomenon are discussed.

PMID- 29319856
TI  - Julian Ormond Smith.

PMID- 29319858
TI  - Visit of the Sims Commonwealth Professor.

PMID- 29319857
TI  - Extramedullary Plasmacytoma of the Gastro-intestinal Tract.
AB  - A case of plasmacytoma affecting the terminal small bowel is described. This is a
      rare condition, and its importance lies in its relationship to other myelomatous
      pathological conditions. In the case reported it would appear that the tumour
      arose primarily in the small bowel and that the bone marrow remained normal.

PMID- 29319859
TI  - Acinic Cell Carcinoma of the Parotid Gland.
AB  - Acinic cell carcinoma of the parotid gland is a rare neoplasm. The first
      described case is ascribed to Nasse, who in 1892 reported four "adenomas" of the
      parotid gland, one of which presented the features of the neoplasm now reported.

PMID- 29319860
TI  - Non-functioning Palliative Gastro-enterostomy.
AB  - The cases of three patients are reported in whom palliative gastro-enterostomy
      failed to provide adequate drainage, although no mechanical obstruction was found
      on reoperation. It appeared that local propulsive failure was responsible.
      Details of a technique to reduce stasis at the anastomotic site are suggested,
      and the use of sympathetic blocking drugs is proposed in the treatment of the
      established case.

PMID- 29319861
TI  - Carcinoid Tumours of the Rectum1.
AB  - A personal canvass conducted in Queensland revealed but five cases of rectal
      carcinoid. The nature of these lesions is discussed, and an attitude towards
      their management is expressed.

PMID- 29319862
TI  - Notes on Mycobacterium Ulcerans.
AB  - A record is given of the events leading to the discovery, the cultivation, and
      the animal transmission of Mycobacterium ulcerans, the causative organism of the
      "Bairnsdale ulcer", together with a discussion on the possible animal hosts and
      vectors. It is suggested as a mailer of speculation that the insectivorous bats
      may be incriminated as the natural hosts, and that bed-bugs or related bugs,
      parasitic on bats, may be the vectors.

PMID- 29319863
TI  - Spontaneous Urinary Extravasation: The Problems of Diagnosis and Management.
AB  - Spontaneous extravasation of urine is becoming more frequently recognised. When
      associated with rupture of the renal pelvis it is more likely to present to a
      general surgeon as an "acute abdomen" than to a urological surgeon, and unless
      suspected early will not be diagnosed until after laparotomy has been performed.
      The case presented demonstrates many of the problems in the diagnosis of this
      condition, and the management is discussed.

PMID- 29319864
TI  - The History of the Royal Australasian College of Surgeons from 1935 to 1960.

PMID- 29319865
TI  - Massive Ascites Due to Pancreatic Stones.
AB  - A case of massive pancreatic ascites due to stones impacted in the head of the
      pancreas is described. The problems in differential diagnosis are outlined.
      Treatment consisting of transduodenal removal of the stones, sphincterotomy and
      gastrojejunostomy was followed by complete disappearance of symptoms and freedom
      from farther episodes of pancreatitis.

PMID- 29319866
TI  - Subdural Empyema.
AB  - Subdural empyema is a distinct clinical entity not uncommon in Ceylon. Forty
      seven cases have been analysed. The commonest sources of infection are otitis
      media and frontal sinusitis. These empyemas are often complicated by cortical
      thrombophlebitis, meningitis and intracerebral abscesses. The symptomatology is
      difficult to differentiate clinically from that of other forms of intracranial
      suppuration. Percutaneous carotid angiography is the investigation of choice. The
      treatment consists of surgical evacuation of pus combined with correct antibiotic
      therapy and skilled nursing. Our mortality of 25.5% was due to uncontrollable
      associated infections, usually the result of late referral.

PMID- 29319867
TI  - Aorto-Caval Fistula: Successful Management of Two Cases.
AB  - Two cases of aorto-caval fistula resulting from spontaneous rupture of an aortic
      aneurysm into the inferior vena cava are described. Although both patients showed
      the classical signs of a pulsatile abdominal mass with a palpable thrill and a
      continuous murmur, and the site of the communication was the same in both cases,
      only the first showed obvious signs of a massive arteriovenous fistula, with a
      collapsing pulse and severe oliguria promptly cured by correction of the fistula.
      The second patient illustrates the ability of one elderly patient to survive a
      series of disasters in aneurysm surgery, namely frank rupture of the aneurysm,
      high output renal failure, caval thrombosis and intraperitoneal suppuration.

PMID- 29319868
TI  - The Bairnsdale Ulcer.
AB  - A record is given of the first known cases of Bairnsdale ulcer and its early
      recognition as a clinical entity. The treatment evolved by excision and skin
      grafting before the final identification of the causative organism is also
      described.

PMID- 29319869
TI  - The Use of Trimethoprim-Sulphamethoxazole in the Treatment of Complicated Urinary
      Tract Infection.
AB  - Fifty patients attending the urological department of the Meath Hospital and
      County Dublin Infirmary, Eire, were treated with the new chemotherapeutic agent,
      trimethoprim-sulphamelhoxazole. Clinical and bacteriological studies were carried
      out at the end of the course of treatment and at follow-up four weeks later. The
      majority of urinary pathogens were found to be sensitive to this preparation, and
      the development of resistant strains was minimal. The drug was found to be
      effective when administered for seven days, and side-effects occurred in one
      patient only.

PMID- 29319870
TI  - The Experimental Application of Microsurgical Techniques to Internal Mammary to
      Coronary Artery Anastomosis.
AB  - Obstructive coronary artery disease is in many patients a disease of the proximal
      arteries. Saphenous vein bypass grafts have been satisfactorily performed into
      vessels of diameters of 2.5 mm and above. A certain proportion of patients exist,
      however, in whom the only vessels available for grafting are of diameters of less
      than 2 mm. The purpose of this study was to test the feasibility of performing
      internal mammary to coronary artery anastomosis in the dog in vessels of
      diameters of 1-2 mm, using the operating microscope The study indicates that it
      is technically possible to perform these anastomoses with an acceptable immediate
      patency rate.

PMID- 29319871
TI  - Winter blues, spring fever and major depression: Are they the same or different.

PMID- 29319874
TI  - Fairness and Transparency.

PMID- 29319875
TI  - Association Between Sensory Impairment and Dementia in Older Adults: Evidence
      from China.
AB  - OBJECTIVES: To determine the association between sensory impairment and dementia
      in Chinese older adults. DESIGN: Cross-sectional. SETTING: Older adults in 31
      provinces of China. PARTICIPANTS: Individuals aged 65 and older (N = 250,752).
      MEASUREMENTS: Psychiatrists ascertained dementia based on the International
      Classification of Diseases, 10th Revision. Sensory impairment was measured as
      only hearing impairment, only vision impairment, and combined sensory impairment
      (combined hearing and vision impairment). Hearing impairment was defined as
      greater than 40 dB loss in the better ear according to the standard of the World
      Health Organization (WHO) Prevention of Deafness and Hearing Impairment (PDH)
      standard 97.3. Ophthalmologists assessed vision impairment according to the WHO
      best-corrected visual acuity (BCVA) criteria (low vision: 0.05<=BCVA <=0.29;
      blindness: no light perception <= BCVA <0.05, visual field less than 10 degrees;
      the better-seeing eye). RESULTS: The prevalence of dementia was 0.41% (95% CI =
      0.39-0.44%) without sensory impairment, 0.83% (95% CI = 0.70-0.99%) with only
      visual impairment, 0.61 (95% CI = 0.53-0.71%) with only hearing impairment, and
      1.27% (95% CI = 1.00-1.61%) with combined sensory impairments. After adjusting
      for sociodemographic characteristics, vision impairment (odds ratio (OR) = 1.58,
      95% CI = 1.28-1.96) and combined sensory impairments (OR = 1.64, 95% CI = 1.23
      2.20) were associated with greater risk of severe to extremely severe dementia.
      Hearing impairment was not significantly associated with dementia. CONCLUSION:
      Sensory impairments are associated with greater risk of dementia in Chinese older
      adults. Studies are needed to further explore the pathway of this association in
      Chinese elderly adults and to provide suggestions to improve health status for
      this population.

PMID- 29319876
TI  - No Expiration Date on the Association Between Physical Activity and Mortality.

PMID- 29319877
TI  - Editorial: With tree nut sensitization, take the current when it serves, or lose
      our ventures.

PMID- 29319878
TI  - The Benefits of Reviewing.

PMID- 29319879
TI  - Cardiorespiratory fitness and age-related arterial stiffness in women with
      systemic lupus erythematosus.
AB  - BACKGROUND: The aim of this study was twofold: (i) to examine the association of
      cardiorespiratory fitness with arterial stiffness in women with systemic lupus
      erythematosus; (ii) to assess the potential interaction of cardiorespiratory
      fitness with age on arterial stiffness in this population. MATERIALS AND METHODS:
      A total of 49 women with systemic lupus erythematosus (mean age 41.3 [standard
      deviation 13.8] years) and clinical stability during the previous 6 months were
      included in the study. Arterial stiffness was assessed through pulse wave
      velocity (Mobil-O-Graph(r) 24 hours pulse wave velocity monitor).
      Cardiorespiratory fitness was estimated with the Siconolfi step test and the 6
      minute walk test. RESULTS: Cardiorespiratory fitness was inversely associated
      with pulse wave velocity in crude analyses (P < .05), although this relationship
      was attenuated when age and other cardiovascular risk factors were controlled.
      There was a cardiorespiratory fitness * age interaction effect on pulse wave
      velocity, regardless of the test used to estimate cardiorespiratory fitness (P <
      .001 for the Siconolfi step test; P = .005 for the 6-minute walk test),
      indicating that higher cardiorespiratory fitness was associated with a lower
      increase in pulse wave velocity per each year increase in age. CONCLUSIONS: The
      results of this study suggest that cardiorespiratory fitness might attenuate the
      age-related arterial stiffening in women with systemic lupus erythematosus and
      might thus contribute to the primary prevention of cardiovascular disease in this
      population. As the cross-sectional design precludes establishing causal
      relationships, future clinical trials should confirm or contrast these findings.

PMID- 29319880
TI  - Competing Risks of Fracture and Death in Older Adults with Chronic Kidney
      Disease.
AB  - OBJECTIVES: To examine whether chronic kidney disease (CKD) at any stage is
      associated with fracture risk after adjusting for competing mortality and to
      determine whether age or race modify the relationship between CKD and fracture
      risk. DESIGN: Prospective cohort study. SETTING: Department of Veterans Affairs
      (VA) national healthcare system. PARTICIPANTS: Men receiving VA primary care aged
      65 and older with no history of fracture or osteoporosis therapy (N = 712, 918).
      MEASUREMENTS: We determined CKD stage from baseline estimated glomerular
      filtration rate (eGFR). Participants were followed for up to 10 years for
      occurrence of any fracture or death. We ascertained fractures and covariates from
      VA medical records and Medicare claims. RESULTS: Of the 356,459 older veterans
      with CKD (defined as eGFR <60 mL/min per 1.73 m2 ), 15.7% (n = 56,032)
      experienced a fracture, and 43.0% (n = 153,438) died over a median time at risk
      of 5.2 years. Veterans with CKD Stages 3 to 5 had a greater risk of death than
      those without CKD, which biased estimates from traditional survival models.
      Competing risk models showed that Stage 3 CKD was associated with greater hazard
      (adjusted subdistribution hazard ratio (sdHR) = 1.07, 95% confidence interval
      (CI) = 1.02-1.11) of fracture (than those without CKD) and a trend toward greater
      hazard for Stage 4 (sdHR = 1.07, 95% CI = 0.94-1.22) and Stage 5 (sdHR = 1.31,
      95% CI = 0.97-1.77) CKD. Age, race, and bone mineral density did not modify the
      relationship between CKD and fracture risk. CONCLUSIONS: In older male veterans,
      CKD, including Stage 3, is associated with a moderately greater fracture risk
      irrespective of age, race, or bone mineral density.

PMID- 29319881
TI  - Systemic IL-2/anti-IL-2Ab complex combined with sublingual immunotherapy
      suppresses experimental food allergy in mice through induction of mucosal
      regulatory T cells.
AB  - BACKGROUND: Therapeutic tolerance restoration has been proven to modify food
      allergy in patients and animal models and although sublingual immunotherapy
      (SLIT) has showed promise, combined therapy may be necessary to achieve a strong
      and long-term tolerance. AIMS: In this work, we combined SLIT with systemic
      administration of IL-2 associated with an anti-IL-2 monoclonal antibody (IL
      2/anti-IL-2Ab complex or IL-2C) to reverse the IgE-mediated experimental allergy.
      MATERIALS AND METHODS: Balb/c mice were sensitized with cholera toxin and milk
      proteins and orally challenged with allergen to elicit hypersensitivity
      reactions. Then, allergic mice were treated with a sublingual administration of
      very low amounts of milk proteins combined with intraperitoneal injection of low
      doses of IL-2C. The animals were next re-exposed to allergens and mucosal as well
      as systemic immunological parameters were assessed in vivo and in vitro. RESULTS:
      The treatment reduced serum specific IgE, IL-5 secretion by spleen cells and
      increased IL-10 and TGF-beta in the lamina propria of buccal and duodenal mucosa.
      We found an augmented frequency of IL-10-secreting CD4+ CD25+ Foxp3+ regulatory T
      cells (Treg) in the submaxilar lymph nodes and buccal lamina propria. Tregs were
      sorted, characterized and adoptively transferred to naive mice, which were
      subsequently sensitized. No allergy was experienced in these mice and we
      encouragingly discovered a faster and more efficient tolerance induction with the
      combined therapy compared with SLIT. CONCLUSION: The combination of two
      therapeutic strategies rendered Treg-mediated tolerance more efficient compared
      to individual treatments and reversed the established IgE-mediated food allergy.
      This approach highlights the ability of IL-2C to expand Tregs, and it may
      represent a promising disease-modifying therapy for managing food allergy.

PMID- 29319882
TI  - Oral myeloid cells uptake allergoids coupled to mannan driving Th1/Treg responses
      upon sublingual delivery in mice.
AB  - BACKGROUND: Polymerized allergoids coupled to nonoxidized mannan (PM-allergoids)
      may represent novel vaccines targeting dendritic cells (DCs). PM-allergoids are
      better captured by DCs than native allergens and favor Th1/Treg cell responses
      upon subcutaneous injection. Herein we have studied in mice the in vivo
      immunogenicity of PM-allergoids administered sublingually in comparison with
      native allergens. METHODS: Three immunization protocols (4-8 weeks long) were
      used in Balb/c mice. Serum antibody levels were tested by ELISA. Cell responses
      (proliferation, cytokines, and Tregs) were assayed by flow cytometry in spleen
      and lymph nodes (LNs). Allergen uptake was measured by flow cytometry in myeloid
      sublingual cells. RESULTS: A quick antibody response and higher IgG2a/IgE ratio
      were observed with PM-allergoids. Moreover, stronger specific proliferative
      responses were seen in both submandibular LNs and spleen cells assayed in vitro.
      This was accompanied by a higher IFNgamma/IL-4 ratio with a quick IL-10
      production by submandibular LN cells. An increase in CD4+ CD25high FOXP3+ Treg
      cells was detected in LNs and spleen of mice treated with PM-allergoids. These
      allergoids were better captured than native allergens by antigen-presenting
      (CD45+ MHC-II+ ) cells obtained from the sublingual mucosa, including DCs (CD11b+
      ) and macrophages (CD64+ ). Importantly, all the differential effects induced by
      PM-allergoids were abolished when using oxidized instead of nonoxidized PM
      allergoids. CONCLUSION: Our results demonstrate for the first time that PM
      allergoids administered through the sublingual route promote the generation of
      Th1 and FOXP3+ Treg cells in a greater extent than native allergens by mechanisms
      that might well involve their better uptake by oral antigen-presenting cells.

PMID- 29319883
TI  - Trait-specific processes of convergence and conservatism shape ecomorphological
      evolution in ground-dwelling squirrels.
AB  - Our understanding of mechanisms operating over deep timescales to shape
      phenotypic diversity often hinges on linking variation in one or few trait(s) to
      specific evolutionary processes. When distinct processes are capable of similar
      phenotypic signatures, however, identifying these drivers is difficult. We
      explored ecomorphological evolution across a radiation of ground-dwelling
      squirrels whose history includes convergence and constraint, two processes that
      can yield similar signatures of standing phenotypic diversity. Using four
      ecologically relevant trait datasets (body size, cranial, mandibular, and
      molariform tooth shape), we compared and contrasted variation, covariation, and
      disparity patterns in a new phylogenetic framework. Strong correlations existed
      between body size and two skull traits (allometry) and among skull traits
      themselves (integration). Inferred evolutionary modes were also concordant across
      traits (Ornstein-Uhlenbeck with two adaptive regimes). However, despite these
      broad similarities, we found divergent dynamics on the macroevolutionary
      landscape, with phenotypic disparity being differentially shaped by convergence
      and conservatism. Such among-trait heterogeneity in process (but not always
      pattern) reiterates the mosaic nature of morphological evolution, and suggests
      ground squirrel evolution is poorly captured by single process descriptors. Our
      results also highlight how use of single traits can bias macroevolutionary
      inference, affirming the importance of broader trait-bases in understanding
      phenotypic evolutionary dynamics.

PMID- 29319884
TI  - Similar localization of conformational IgE epitopes on the house dust mite
      allergens Der p 5 and Der p 21 despite limited IgE cross-reactivity.
AB  - BACKGROUND: Due to high IgE recognition frequency and high allergenic activity,
      Der p 5 and Der p 21 are clinically important house dust mite (HDM) allergens.
      The objective of this study was to characterize the immunodominant IgE epitopes
      of Der p 5 and Der p 21 responsible for their high allergenic activity. METHODS:
      A panel of 12 overlapping peptides spanning the Der p 5 and Der p 21 sequence
      were synthesized to search for sequential IgE epitopes by direct testing for
      allergic patients' IgE reactivity. Peptide-specific antibodies raised in rabbits
      were used in inhibition studies for localizing conformational IgE epitopes which
      were visualized on the surfaces of the allergen structures by molecular
      modelling. IgE cross-reactivity between the allergens was investigated by IgE
      inhibition studies. RESULTS: Immunodominant IgE epitopes defined by allergic
      patients' IgE on Der p 5 and Der p 21 were primarily of the conformational,
      discontinuous type including N- and C-terminal portions of the protein. They
      could be located on each allergen on one area with similar localization, but
      despite similar structure of the allergens, no relevant IgE cross-reactivity
      could be detected. CONCLUSION: Our study shows that Der p 5 and Der p 21 contain
      a major conformational IgE epitope-containing area located on similar portions of
      their structure, but they lack relevant IgE cross-reactivity. These data are
      important for the development of modern allergy vaccines based on defined
      molecules for allergen-specific immunotherapy of HDM allergy.

PMID- 29319886
TI  - EAACI guidelines on allergen immunotherapy-Out with the old and in with the new.

PMID- 29319885
TI  - Patient selection in major upper abdominal surgery for cancer in octogenarians.

PMID- 29319887
TI  - Depressed mood is associated with loss of productivity in allergic rhinitis.
AB  - Allergic rhinitis (AR) is associated with significant decreases in quality of
      life and productivity losses. We hypothesized that symptoms of AR may
      differentially associate with lost productivity due to AR. We performed a cross
      sectional cohort study of 105 prospectively recruited patients with persistent
      AR. AR control, severity of depressed mood, and sinonasal symptoms were assessed
      with the Rhinitis Control Assessment Test (RCAT), Patient Health Questionnaire
      (PHQ-2), and the 22-item Sinonasal Outcome Test (SNOT-22), respectively. Lost
      productivity was assessed by asking the number of days of work/school missed due
      to AR in the last 3 months. Patients missed a mean of 1.5 days (SD:2.9) of work
      or school. Lost productivity was associated with PHQ-2 (adjusted linear
      regression coefficient [beta] = .68, 95% CI: 0.20-1.15, P = .007) analysis but
      not SNOT-22 or RCAT scores. Productivity losses due to AR are associated with
      severity of depressed mood rather than classic nasal or extra-nasal symptoms of
      AR.

PMID- 29319888
TI  - Formation of Cyanamide-Glyoxal Oligomers in Aqueous Environments Relevant to
      Primeval and Astrochemical Scenarios: A Spectroscopic and Theoretical Study.
AB  - The condensation of cyanamide and glyoxal, two well-known prebiotic monomers, in
      an aqueous phase has been investigated in great detail, demonstrating the
      formation of oligomeric species of varied structure, though consistent with
      generalizable patterns. This chemistry involving structurally simple substances
      also illustrates the possibility of building molecular complexity under
      prebiotically plausible conditions, not only on Earth, but also in
      extraterrestrial scenarios. We show that cyanamide-glyoxal reactions in water
      lead to mixtures comprising both acyclic and cyclic fragments, largely based on
      fused five- and six-membered rings, which can be predicted by computation.
      Remarkably, such a mixture could be identified using high-resolution electrospray
      ionization (ESI) mass spectrometry and spectroscopic methods. A few mechanistic
      pathways can be postulated, most involving the intermediacy of glyoxal cyanoimine
      and further chain growth, thus increasing the diversity of the observed products.
      This rationale is supported by theoretical analyses with clear-cut identification
      of all of the stationary points and transition-state structures. The properties
      and structural differences of oligomers obtained under thermodynamic conditions
      in water as opposed to those isolated by precipitation from organic media are
      also discussed.

PMID- 29319889
TI  - Epitope-Targeted Macrocyclic Peptide Ligand with Picomolar Cooperative Binding to
      Interleukin-17F.
AB  - The IL-17 cytokine family is associated with multiple immune and autoimmune
      diseases and comprises important diagnostic and therapeutic targets. This work
      reports the development of epitope-targeted ligands designed for differential
      detection of human IL-17F and its closest homologue IL-17A. Non-overlapping and
      unique epitopes on IL-17F and IL-17A were identified by comparative sequence
      analysis of the two proteins. Synthetic variants of these epitopes were utilized
      as targets for in situ click screens against a comprehensive library of synthetic
      peptide macrocycles with 5-mer variable regions. Single generation screens
      yielded selective binders for IL-17F and IL-17A with low cross-reactivity.
      Macrocyclic peptide binders against two distinct IL-17F epitopes were coupled
      using variable length chemical linkers to explore the physical chemistry of
      cooperative binding. The optimized linker length yielded a picomolar affinity
      binder, while retaining high selectivity. The presented method provides a
      rational approach towards targeting discontinuous epitopes, similar to what is
      naturally achieved by many B cell receptors.

PMID- 29319890
TI  - Two novel unstable hemoglobin variants due to in-frame deletions of key amino
      acids in the beta-globin chain.
AB  - Hemoglobinopathies are the most common autosomal recessive disorders and are
      mostly inherited in a recessive manner. However, certain mutations can affect the
      globin chain stability, leading to dominant forms of thalassemia. The aim of this
      work was the molecular and structural characterization of two heterozygous in
      frame deletions, leading to beta-globin variants in pediatric patients in
      Argentina. The HBB gene of the probands and their parents was sequenced, and
      other markers of globin chain imbalance were analyzed. Several structural
      analyses were performed, and the effect of the mutations on the globin chain
      stability was analyzed. In Hb JC-Paz, HBB:c.29_37delCTGCCGTTA (p.Ala10_Thr12del),
      detected in an Argentinean boy, one alpha-helix turn is expected to be lost. In
      Hb Tavapy, HBB:c.182_187delTGAAGG (p.Val60_Lys61del), the deleted residues are
      close to distal histidine (His63) in the heme pocket. Both mutations are
      predicted to have a destabilizing effect. The development of computational
      structural models and bioinformatics algorithms is expected to become a useful
      tool to understand the impact of the mutations leading to dominant thalassemia.

PMID- 29319891
TI  - Teicoplanin anaphylaxis associated with surgical prophylaxis.
AB  - AIMS: The aim of this paper is to determine the rate of true anaphylaxis to
      teicoplanin. METHODS: A case-series including all suspected anaphylactic
      reactions attributed to teicoplanin anaphylaxis within a single institution over
      a 29-month period were categorised according to the probability of true IgE
      mediated anaphylaxis using previously published criteria. The number of patients
      who received teicoplanin was determined and used to calculate the rate of IgE
      mediated anaphylaxis. RESULTS: Approximately 18 800-19 600 patients received
      teicoplanin during the study period, during which there were 14 cases of
      suspected anaphylaxis attributed to the administration of teicoplanin: five were
      categorised as definite IgE-mediated anaphylaxis, four as probable, two as
      uncertain and three were excluded. Of the excluded cases, two were found to have
      positive intradermal skin testing to alternative agents (rocuronium and
      chlorhexidine), and one did not meet the published clinical criteria. We
      therefore calculated the rate of IgE-mediated anaphylaxis to be between 0.046%
      and 0.059% (equating to between 1:2088 and 1:1655). CONCLUSIONS: This is the
      first study to calculate a rate of IgE-mediated anaphylaxis to teicoplanin in
      clinical practice. Our case series suggests that these life-threatening reactions
      occur less commonly than reported by the manufacturers. Mast cell tryptase is
      unreliable when used to predict the likelihood of IgE-mediated anaphylaxis to
      teicoplanin.

PMID- 29319892
TI  - Role of cytochrome P450 2B sequence variation and gene copy number in
      facilitating dietary specialization in mammalian herbivores.
AB  - Theory postulates that dietary specialization in mammalian herbivores is enabled
      by a specialized set of liver enzymes that process the high concentrations of
      similar plant secondary metabolites (PSMs) in the diets of specialists. To
      investigate whether qualitative and quantitative differences in detoxification
      mechanisms distinguish dietary specialists from generalists, we compared the
      sequence diversity and gene copy number of detoxification enzymes in two woodrat
      species: a generalist, the white-throated woodrat (Neotoma albigula) and a
      juniper specialist, Stephens' woodrat (N. stephensi). We focused on enzymes in
      the cytochrome P450 subfamily 2B (CYP2B), because previous research suggests this
      subfamily plays a key role in the processing of PSMs. For both woodrat species,
      we obtained and sequenced CYP2B cDNA, generated CYP2B phylogenies, estimated
      CYP2B gene copy number and created a homology model of the active site. We found
      that the specialist possessed on average ~5 more CYP2B gene copies than the
      generalist, but the specialist's CYP2B sequences were less diverse. Phylogenetic
      analysis of putative CYP2B homologs resolved woodrat species as reciprocally
      monophyletic and suggested evolutionary convergence of distinct homologs on
      similar key amino acid residues in both species. Homology modelling of the CYP2B
      enzyme suggests that interspecific differences in substrate preference and
      function likely result from amino acid differences in the enzyme active site. The
      characteristics of CYP2B in the specialist, that is greater gene copy number
      coupled with less sequence variation, are consistent with specialization to a
      narrow range of dietary toxins.

PMID- 29319893
TI  - Possible role of CYP2B6 genetic polymorphisms in ifosfamide-induced
      encephalopathy: report of three cases.
AB  - Ifosfamide (IFA) is a potent alkylating antitumoral agent, but its use is limited
      by neurological side effects. IFA is a racemic mixture of two enantiomeric forms,
      R-IFA and S-IFA with a stereoselective metabolism by CYP3A4 and CYP2B6, leading
      either to bioactive or to toxic pathways. In three consecutive cases of pediatric
      patients who exhibited IFA-induced encephalopathy (IIE), genotyping of clinically
      relevant single-nucleotide polymorphisms associated with decreased CYP3A4 and
      CYP2B6 activities was performed. Genetic investigations revealed the presence of
      CYP2B6 rs4803419 (C>T) in one patient while the two others carried the CYP2B6*6
      allelic variant. All patients carried CYP3A4 wild-type genotype (CYP3A4*1/*1).
      Because CYP2B6-deficient alleles may be responsible for an increased conversion
      of S-IFA into neurotoxic metabolites, screening for CYP2B6 polymorphisms may help
      to avoid IIE and improve clinical outcomes.

PMID- 29319894
TI  - Antibiotic prescribing for endodontic therapies: a comparative survey between
      general dental practitioners and final year Bachelor of Dental Surgery students
      in Cardiff, UK.
AB  - AIM: To evaluate the views of final year dental surgery students (BDS; G1) at
      Cardiff University and general dental practitioners (GDPs; G2) within the
      geographic area of Cardiff, Wales, on antibiotic prescribing for endodontic
      conditions, and investigate the potential differences between the two groups.
      METHODS: A cross-sectional online questionnaire-based survey of 12 qualitative
      and quantitative questions was distributed to 76 final year BDS Cardiff
      University students and 55 dental practices within Cardiff, UK. Six questions
      recorded general information, and the remaining questions included a series of
      hypothetical clinical scenarios, where the participants were asked to state
      whether they would or would not prescribe antibiotics. The data were analysed
      using spss version 23 to produce descriptive statistics, contingency tables and
      to run chi-square (chi2) tests, Fisher's exact tests and relative risk
      calculations. RESULTS: The response rate was 60% (n = 79). All G1 participants
      were aware of the consequences of antibiotic overuse. Approximately 60% of
      responders were aware of guidelines for antibiotic use in endodontic therapies,
      and 83% would only use antibiotics for a limited selection of patients (e.g.
      patients with systemic complications). G1 responses to clinical scenarios
      indicated overall that they were comparable to the ideal answers except for acute
      apical abscess (64% believed that antibiotics were indicated). The majority of G2
      were aware of the consequences of antibiotic overuse. Only 28% of G2 were aware
      of guidelines for antibiotic use in endodontic therapies. Overall responses
      revealed that antibiotics would be prescribed for: systemic complications (78%),
      acute apical abscess (72%) and symptomatic apical periodontitis (28%). The
      clinical scenarios revealed G1 were more likely to prescribe antibiotics compared
      to G2 for cases of necrotic pulp with symptomatic apical periodontitis without
      systemic complications (incorrect answer) and less likely to other clinical
      scenarios such as necrotic pulp and asymptomatic apical periodontitis for
      patients with a history of rheumatic fever (ideal answers), symptomatic
      irreversible/reversible pulpitis, failure to achieve anaesthesia, chronic apical
      abscess for patients with diabetes. The recognition of antibiotic prescription
      for cases with signs of spreading infection was more evident in G2. CONCLUSION:
      Final year undergraduate students were aware of the antibiotic resistance crisis,
      although a third was not aware of guidelines for use of antibiotics in endodontic
      conditions; their responses to clinical scenario were generally compatible with
      the guidelines. General dentists were less aware of the implications of overuse
      of antibiotics and the existence of guidelines, and their responses were
      occasionally incompatible with antibiotic guidelines for endodontic therapies.

PMID- 29319895
TI  - The onset of fretting at the head-stem connection in hip arthroplasty is affected
      by head material and trunnion design under simulated corrosion conditions.
AB  - Mechanically assisted crevice corrosion (MACC) is a mechanism for trunnion damage
      in total hip arthroplasties (THAs). Retrieval studies have shown reduced MACC
      related damage for ceramic heads compared with cobalt-chromium (CoCr) heads. We
      propose that ceramic heads demonstrate fretting at higher cyclic compressive
      loads than CoCr heads on titanium alloy trunnions in a simulated corrosion model.
      A closed electrochemical chamber was used to measure fretting current onset loads
      for two modern titanium alloy trunnions (Zimmer 12/14 and Stryker V-40) in which
      trunnion failure has been reported. Ceramic and CoCr alloy 36 + 0 mm heads were
      impacted on each trunnion and cyclically loaded at 3 Hz with increasing magnitude
      from 100 to 3,400 N for 540 cycles. Onset load was the cyclic compressive load at
      which the slope of the average fretting current increased significantly. A CoCr
      head with V40 trunnion demonstrated the lowest onset load (1,400 N), while the
      V40 trunnion with a ceramic head showed the highest onset load (2,200 N).
      Significant differences occurred in average fretting current between head
      materials for V40 trunnions (p < 0.001) at loads over 2,000 N. CoCr-12/14 and
      ceramic-12/14 couples demonstrated similar onset loads (2,000 N). All head
      trunnion combinations showed cyclical fretting response to loading at 100 N. Head
      material composition was observed to increase fretting at the taper junction but
      the effect was taper geometry dependent. Using ceramic heads may reduce the
      phenomena of trunnion fretting and corrosion but the effect of both trunnion
      geometry and metallurgy warrants further investigation. Statement of clinical
      significance: Trunnion corrosion may occur with titanium alloy stems regardless
      of the head material used. (c) 2017 Orthopaedic Research Society. Published by
      Wiley Periodicals, Inc. J Orthop Res 36:1630-1636, 2018.

PMID- 29319896
TI  - Skin inflammation exacerbates food allergy symptoms in epicutaneously sensitized
      mice.
AB  - BACKGROUND: Cutaneous exposure to food antigen through impaired skin barrier has
      been shown to induce epicutaneous sensitization, thereby causing IgE-mediated
      food allergies. OBJECTIVE: We examined whether skin barrier impairment following
      epicutaneous sensitization exacerbates food allergies. METHODS: BALB/c mice were
      epicutaneously sensitized by repeated application of ovalbumin (OVA) to MC903
      pretreated ear skin for 48 hours weekly and then intragastrically challenged with
      OVA. After the first oral challenge, the skin barrier was disrupted with topical
      application of MC903 or by tape-stripping. Mice were monitored for changes in
      body temperature and the occurrence of diarrhea after undergoing the second oral
      challenge. Serum levels of mouse mast cell protease-1 (mmcp1) and OVA-specific
      IgE, IgG1, IgG2a antibodies and OVA-specific IgA levels in intestinal lavage
      fluid were measured by ELISA. Tissue accumulation of eosinophils was determined
      histologically. RESULTS: Epicutaneously sensitized mice developed anaphylaxis
      after intragastric challenge, as evidenced by diarrhea, decreased body
      temperature, and increased serum mmcp1 levels. Skin barrier disruption by MC903
      treatment or tape-stripping exacerbated allergic reactions induced by oral
      challenge. MC903 treatment increased serum baseline and postchallenge mmcp1
      levels. Topical pretreatment with dexamethasone alleviated allergic reactions
      that were exacerbated by MC903 treatment. CONCLUSION: Even after eliminating
      exposure to the antigen, inflammation from skin barrier disruption can exacerbate
      the severity of food allergy symptoms. Serum baseline mmcp1 levels might be an
      effective marker for predicting the severity of antigen-induced allergic
      symptoms.

PMID- 29319897
TI  - Application of a physiologically-based pharmacokinetic model for the prediction
      of bumetanide plasma and brain concentrations in the neonate.
AB  - Bumetanide is a loop diuretic that is proposed to possess a beneficial effect on
      disorders of the central nervous system, including neonatal seizures. Therefore,
      prediction of unbound bumetanide concentrations in the brain is relevant from a
      pharmacological prospective. A physiologically-based pharmacokinetic (PBPK) model
      was developed for the prediction of bumetanide disposition in plasma and brain in
      adult and paediatric populations. A compound file was built for bumetanide
      integrating physicochemical data and in vitro data. Bumetanide concentration
      profiles were simulated in both plasma and brain using the Simcyp PBPK model.
      Simulations of plasma bumetanide concentrations were compared against plasma
      levels published in the literature. The model performance was verified with data
      from adult studies before predictions in the paediatric population were
      undertaken. The adult and paediatric intravenous models predicted pharmacokinetic
      factors, namely area under the concentration-time curve, maximum concentration in
      plasma and time to maximum plasma concentration, within two-fold of observed
      values. However, predictions of plasma concentrations within the neonatal
      intravenous model did not produce a good fit with the observed values. The PBPK
      approach used in this study produced reasonable predictions of plasma
      concentrations of bumetanide, except in the critically ill neonatal population.
      This PBPK model requires more information regarding metabolic intrinsic clearance
      and transport parameters prior to further validation of drug disposition
      predictions in the neonatal population. Given the lack of information surrounding
      certain parameters in this special population, the model is not appropriately
      robust to support the recommendation of a suitable dose of bumetanide for use as
      an adjunct antiepileptic in neonates.

PMID- 29319898
TI  - What Is Your Diagnosis? Eyelid mass in a dog.

PMID- 29319899
TI  - Usefulness of asthma predictive index in ascertaining asthma status of children
      using medical records: An explorative study.
AB  - BACKGROUND: Frequent wheezing in original asthma predictive index (API) was
      defined by parental report of recurrent wheezing within 1 year during the first 3
      years of life. The nature of frequent wheezing in children, particularly aged
      over 3 years, has not been studied. We aimed to assess the frequency and interval
      of wheezing to define frequent wheezing in ascertaining asthma for children using
      medical records. METHODS: Among children who participated in a previous study (n
      = 427), all wheezing episodes documented in medical records were collected for
      children who had >=2 wheezing episodes PLUS met one major criterion or two minor
      criteria of API. We compared the distribution of known risk factors for asthma
      between subjects having two consecutive wheezing episodes with shorter interval
      (<=1 year) compared to those with longer interval (1 to 3 years). RESULTS: A
      total of 62 children met API at median age of 2.3 years. During follow-up period
      (median age: 11.3 years), a total of 198 wheezing episodes were observed. 81% of
      wheezing intervals were within 3 years from the earlier wheezing episode,
      including 60% within 1 year. Children who met API based on 1-year interval (n =
      40) vs 1- to 3-year interval (n = 13) appeared to be similar in regard to the
      known risk factors for asthma. CONCLUSIONS: Our exploratory study finding
      suggests that children who had frequent wheezing episodes with longer interval
      (<3 years) need to be considered to be determined as asthma cases when API is
      applied to retrospective medical records. Prospective studies with a larger
      sample size need to replicate this finding.

PMID- 29319900
TI  - Layperson's knowledge and perceptions of irritable bowel syndrome as potential
      barriers to care.
AB  - AIMS: The aim of this study was to describe the layperson's knowledge and
      perceptions regarding the aetiology, pathogenesis, prevalence, medical
      evaluation, diagnosis and treatment of irritable bowel syndrome. BACKGROUND:
      Diagnosis acceptance and adherence to treatment is influenced by the views of the
      patient's social networks. Little is known how these networks influence those
      with irritable bowel syndrome. DESIGN: Cross-sectional study of two-hundred four
      laypersons, ages 18-80 years without an irritable bowel syndrome diagnosis.
      METHODS: Data were collected May 2016-March 2017. Laypersons without a diagnosis
      of IBS self-reported their knowledge and perceptions about IBS. RESULTS/FINDINGS:
      Participants were able to identify many symptoms associated with irritable bowel
      syndrome however held misconceptions regarding the development of irritable bowel
      syndrome as noted by the endorsement of genetics, environment and diet or
      alcohol/smoking behaviours as specific causes. Further misconceptions held
      included the belief that irritable bowel syndrome was associated with an
      increased risk for the development of colon cancer and inflammatory bowel
      disease. Contrary to current guidelines, many thought a gastroenterologist was
      the only person appropriate to diagnose irritable bowel syndrome and objective
      testing, such as colonoscopy, was necessary to establish a diagnosis. CONCLUSION:
      Laypersons have an understanding of the symptoms associated with IBS; however,
      hold numerous misconceptions regarding the aetiology, role of the healthcare
      provider, necessary testing and risks associated with irritable bowel syndrome.
      These misconceptions are inconsistent with current guidelines and practices.
      Establishing partnerships and educating social networks in addition to patients
      may enhance outcomes for those with IBS.

PMID- 29319901
TI  - Gomisin A modulates aging progress via mitochondrial biogenesis in human diploid
      fibroblast cells.
AB  - Gomisin A from the fruit of Schisandra chinensis has many pharmacological
      properties, including hepato-protective, anti-diabetic, and anti-oxidative
      stress. However, the potential benefit of gomisin A is still not well understood,
      especially in aging progression. Therefore, the aim of this study was to clarify
      whether the promotion of mitochondrial biogenesis and autophagy of gomisin A
      affects anti-aging progression, and its mechanism. Intermediate (PD32) human
      diploid fibroblast (HDF) cells were brought to stress-induced premature
      senescence (SIPS) using hydrogen peroxide. Gomisin A inhibited reactive oxygen
      species production even in the SIPS-HDF cells. Gomisin A was also able to
      attenuate the activity of senescence-associated beta-galactosidase and the
      production of pro-inflammatory molecules in the SIPS as well as aged HDF cells.
      The antioxidant activity of gomisin A was determined by recovering the Cu/Zn, Mn
      SOD, and HO-1 expression in the SIPS-HDF cells. In mechanistic aspect, gomisin A
      inhibited the mitogen-activated protein kinase pathway and the translocation of
      nuclear factor kappa B to the nucleus. In addition, gomisin A promoted the
      autophagy and mitochondrial biogenesis factors through the translocation of
      nuclear factor erythroid 2-related factor-2, and inhibited aging progression in
      the SIPS-HDF cells. In summary, the enhanced properties of mitochondrial
      biogenesis and autophagy of gomisin A has a benefit to control age-related
      molecules against SIPS-induced chronic oxidative stress, and gomisin A may be a
      potential therapeutic compound for the enhancement of intracellular homeostasis
      to aging progression.

PMID- 29319902
TI  - What is your diagnosis? Transtracheal wash from a donkey.

PMID- 29319903
TI  - SnS2 /Sb2 S3 Heterostructures Anchored on Reduced Graphene Oxide Nanosheets with
      Superior Rate Capability for Sodium-Ion Batteries.
AB  - Tin disulfide, as a promising high-capacity anode material for sodium-ion
      batteries, exhibits high theoretical capacity but poor practical electrochemical
      properties due to its low electrical conductivity. Constructing heterostructures
      has been considered to be an effective approach to enhance charge transfer and
      ion-diffusion kinetics. In this work, composites of SnS2 /Sb2 S3 heterostructures
      with reduced graphene oxide nanosheets were synthesized by a facile one-pot
      hydrothermal method. When applied as anode material in sodium-ion batteries, the
      composite showed a high reversible capacity of 642 mA h g-1 at a current density
      of 0.2 A g-1 and good cyclic stability without capacity loss in 100 cycles. In
      particular, SnS2 /Sb2 S3 heterostructures exhibited outstanding rate performance
      with capacities of 593 and 567 mA h g-1 at high current densities of 2 and 4 A g
      1 , respectively, which could be ascribed to the dramatically improved Na+
      diffusion kinetics and electrical conductivity.

PMID- 29319904
TI  - Preparation of beta-cyclodextrin-gold nanoparticles modified open tubular column
      for capillary electrochromatographic separation of chiral drugs.
AB  - In this paper, beta-cyclodextrin (beta-CD) modified gold nanoparticles (AuNPs)
      coated open tubular column (OT column) was prepared for capillary
      electrochromatography. The open tubular column was constructed through self
      assembly of gold nanoparticles on 3-mercaptopropyl-trimethoxysilane (MPTMS)
      prederivatized capillary and subsequent modification of thiols beta-cyclodextrin
      (SH-beta-CD). Scanning electron microscopy (SEM), transmission electron
      microscopy (TEM) and ultraviolet visible spectroscopy were carried out to
      characterize the prepared open tubular column and synthesized gold nanoparticles.
      By comparing different coating times of gold nanoparticles and thiols beta
      cyclodextrin, we got the optimal conditions for preparing the open tubular
      column. Also, the separation parameters were optimized including buffer pH,
      buffer concentration and applied voltage. Separation effectiveness of open
      tubular column was verified by the separation of four pairs of drug enantiomers
      including bifonazole, fexofenadine, omeprazole and lansoprazole, and satisfactory
      separation results were achieved for these analytes studied. In addition, the
      column showed good stability and repeatability. The relative standard deviation
      values less than 5% were obtained through intra-day, inter-day, and column-to
      column investigations.

PMID- 29319905
TI  - Claims about abortion and clinical implications lack evidence.

PMID- 29319906
TI  - Consequences of multiple mating-system shifts for population and range-wide
      genetic structure in a coastal dune plant.
AB  - Evolutionary transitions from outcrossing to selfing can strongly affect the
      genetic diversity and structure of species at multiple spatial scales. We
      investigated the genetic consequences of mating-system shifts in the North
      American, Pacific coast dune endemic plant Camissoniopsis cheiranthifolia
      (Onagraceae) by assaying variation at 13 nuclear (n) and six chloroplast (cp)
      microsatellite (SSR) loci for 38 populations across the species range. As
      predicted from the expected reduction in effective population size (Ne ) caused
      by selfing, small-flowered, predominantly selfing (SF) populations had much lower
      nSSR diversity (but not cpSSR) than large-flowered, predominantly outcrossing
      (LF) populations. The reduction in nSSR diversity was greater than expected from
      the effects of selfing on Ne alone, but could not be accounted for by indirect
      effects of selfing on population density. Although selfing should reduce gene
      flow, SF populations were not more genetically differentiated than LF
      populations. We detected five clusters of nSSR genotypes and three groups of
      cpSSR haplotypes across the species range consisting of parapatric groups of
      populations that usually (but not always) differed in mating system, suggesting
      that selfing may often initiate ecogeographic isolation. However, lineage-wide
      genetic variation was not lower for selfing clusters, failing to support the
      hypothesis that selection for reproductive assurance spurred the evolution of
      selfing in this species. Within three populations where LF and SF plants coexist,
      we detected genetic differentiation among diverged floral phenotypes suggesting
      that reproductive isolation (probably postzygotic) may help maintain the striking
      mating-system differentiation observed across the range of this species.

PMID- 29319907
TI  - Aberrant accumulation of ErbB4 in progressive supranuclear palsy.
AB  - AIMS: The human epidermal growth factor receptor family consists of four members
      that belong to the ErbB lineage of proteins (ErbB1-4). Neuregulin-1 (NRG1)/ErbB
      signalling regulates brain development and function. Abnormalities in this
      signalling have been implicated in the aetiology or development of
      neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and
      amyotrophic lateral sclerosis. So, we aimed at investigating whether the
      expression of NRG1 or ErbB proteins are altered in progressive supranuclear palsy
      (PSP). METHODS: The brains of 10 PSP and six control patients were investigated
      by immunohistochemical analysis. RESULTS: Whereas C-terminal ErbB4
      immunoreacitivity was partially but distinctly present in the cytoplasm and/or in
      the nucleus of neurons in control patients, it was rarely observed in the
      neuronal nuclei in PSP patients. In contrast, neurofibrillary tangles, coiled
      bodies and threads were robustly immunoreactive for C-terminal ErbB4 in PSP.
      Double immunofluorescence for C-terminal ErbB4 and phospho-tau revealed co
      localization of these proteins within neuronal and glial inclusions. To the
      contrary, there was no difference in the subcellular localization of NRG1, ErbB1,
      ErbB2, and N-terminal ErbB4 between control and PSP patients. These proteins were
      localized in the cytoplasm of neurons. CONCLUSIONS: Our present results suggest
      that NRG1/ErbB4 signalling could be an important event in the pathogenesis of
      PSP.

PMID- 29319908
TI  - Integrating Bayesian genomic cline analyses and association mapping of
      morphological and ecological traits to dissect reproductive isolation and
      introgression in a Louisiana Iris hybrid zone.
AB  - Hybrid zones provide unique opportunities to examine reproductive isolation and
      introgression in nature. We utilized 45,384 single nucleotide polymorphism (SNP)
      loci to perform association mapping of 14 floral, vegetative and ecological
      traits that differ between Iris hexagona and Iris fulva, and to investigate,
      using a Bayesian genomic cline (BGC) framework, patterns of genomic introgression
      in a large and phenotypically diverse hybrid zone in southern Louisiana. Many
      loci of small effect size were consistently found to be associated with
      phenotypic variation across all traits, and several individual loci were revealed
      to influence phenotypic variation across multiple traits. Patterns of genomic
      introgression were quite heterogeneous throughout the Louisiana Iris genome, with
      I. hexagona alleles tending to be favoured over those of I. fulva. Loci that were
      found to have exceptional patterns of introgression were also found to be
      significantly associated with phenotypic variation in a small number of
      morphological traits. However, this was the exception rather than the rule, as
      most loci that were associated with morphological trait variation were not
      significantly associated with excess ancestry. These findings provide insights
      into the complexity of the genomic architecture of phenotypic differences and are
      a first step towards identifying loci that are associated with both trait
      variation and reproductive isolation in nature.

PMID- 29319909
TI  - Inhibitory effects of sulfonylureas and non-steroidal anti-inflammatory drugs on
      in vitro metabolism of canagliflozin in human liver microsomes.
AB  - Canagliflozin, used to treat type 2 diabetes mellitus (T2DM), is commonly co
      administered with sulfonylureas. The objective of the present study was to
      evaluate the possible inhibitory effect of sulfonylureas and non-steroidal anti
      inflammatory drugs (NSAIDs) on canagliflozin metabolism in vitro. Three
      sulfonylurea derivatives were evaluated as inhibitors: chlorpropamide,
      glimepiride and gliclazide. Two other NSAIDs were used as positive control
      inhibitors: niflumic acid and diclofenac. The rate of formation of canagliflozin
      metabolites was determined by HPLC analysis of in vitro incubations of
      canagliflozin as a substrate with and without inhibitors, using human liver
      microsomes (HLMs). Among sulfonylureas, glimepiride showed the most potent
      inhibitory effect against canagliflozin M7 metabolite formation, with an IC50
      value of 88 MUm, compared to chlorpropamide and gliclazide with IC50 values of
      more than 500 MUm. Diclofenac inhibited M5 metabolite formation more than M7,
      with IC50 values of 32 MUm for M5 and 80 MUm for M7. Niflumic acid showed no
      inhibition activity against M5 formation, but had relatively selective inhibitory
      potency against M7 formation, which is catalysed by UGT1A9, with an IC50 value of
      1.9 MUm and an inhibition constant value of 0.8 MUm. A clinical pharmacokinetic
      interaction between canagliflozin and sulfonylureas is unlikely. However, a
      possible clinically important drug interaction between niflumic acid and
      canagliflozin has been identified.

PMID- 29319910
TI  - Reversal of mecamylamine-induced effects in healthy subjects by nicotine receptor
      agonists: Cognitive and (electro) physiological responses.
AB  - AIMS: Establishing a pharmacological challenge model could yield an important
      tool to understand the complex role of the nicotinic cholinergic system in
      cognition and to develop novel compounds acting on the nicotinic acetylcholine
      receptor. METHODS: This randomized, double-blind, double-dummy, placebo
      controlled, four-way crossover study examined the effects of the nicotinic
      antagonist mecamylamine on a battery of cognitive and neurophysiological test
      with coadministration of a placebo, nicotine or galantamine in order to reverse
      the cognitive impairment caused by mecamylamine. RESULTS: Thirty-three healthy
      subjects received a single oral dose of 30 mg of mecamylamine (or placebo) in
      combination with either 16 mg of oral galantamine or 21 mg of transdermal
      nicotine (or its double-dummy). Mecamylamine 30 mg induced significant
      disturbances of cognitive functions. Attention and execution of visual (fine)
      motor tasks was decreased, short- and long-term memory was impaired and the
      reaction velocity during the test was slower when compared to placebo.
      Mecamylamine 30 mg produced a decrease in posterior alpha and beta power in the
      surface electroencephalogram, effects that were reversed by nicotine
      coadministration. Memory and motor coordination tests could be partially reversed
      by the coadministration of nicotine. CONCLUSIONS: Mecamylamine administration
      induced slowing of the electroencephalogram and produced decrease in performance
      of tests evaluating motor coordination, sustained attention and short- and long
      term memory. These effects could be partially reversed by the coadministration of
      nicotine, and to a lesser extent by galantamine.

PMID- 29319912
TI  - Transcriptomics in the wild: Hibernation physiology in free-ranging dwarf lemurs.
AB  - Hibernation is an adaptive strategy some mammals use to survive highly seasonal
      or unpredictable environments. We present the first investigation on the
      transcriptomics of hibernation in a natural population of primate hibernators:
      Crossley's dwarf lemurs (Cheirogaleus crossleyi). Using capture-mark-recapture
      techniques to track the same animals over a period of 7 months in Madagascar, we
      used RNA-seq to compare gene expression profiles in white adipose tissue (WAT)
      during three distinct physiological states. We focus on pathway analysis to
      assess the biological significance of transcriptional changes in dwarf lemur WAT
      and, by comparing and contrasting what is known in other model hibernating
      species, contribute to a broader understanding of genomic contributions of
      hibernation across Mammalia. The hibernation signature is characterized by a
      suppression of lipid biosynthesis, pyruvate metabolism and mitochondrial
      associated functions, and an accumulation of transcripts encoding ribosomal
      components and iron-storage proteins. The data support a key role of pyruvate
      dehydrogenase kinase isoenzyme 4 (PDK4) in regulating the shift in fuel economy
      during periods of severe food deprivation. This pattern of PDK4 holds true across
      representative hibernating species from disparate mammalian groups, suggesting
      that the genetic underpinnings of hibernation may be ancestral to mammals.

PMID- 29319911
TI  - Genomic islands of differentiation in two songbird species reveal candidate genes
      for hybrid female sterility.
AB  - Hybrid sterility is a common first step in the evolution of postzygotic
      reproductive isolation. According to Haldane's Rule, it affects predominantly the
      heterogametic sex. While the genetic basis of hybrid male sterility in organisms
      with heterogametic males has been studied for decades, the genetic basis of
      hybrid female sterility in organisms with heterogametic females has received much
      less attention. We investigated the genetic basis of reproductive isolation in
      two closely related avian species, the common nightingale (Luscinia megarhynchos)
      and the thrush nightingale (L. luscinia), that hybridize in a secondary contact
      zone and produce viable hybrid progeny. In accordance with Haldane's Rule, hybrid
      females are sterile, while hybrid males are fertile, allowing gene flow to occur
      between the species. Using transcriptomic data from multiple individuals of both
      nightingale species, we identified genomic islands of high differentiation (FST )
      and of high divergence (Dxy ), and we analysed gene content and patterns of
      molecular evolution within these islands. Interestingly, we found that these
      islands were enriched for genes related to female meiosis and metabolism. The
      islands of high differentiation and divergence were also characterized by higher
      levels of linkage disequilibrium than the rest of the genome in both species
      indicating that they might be situated in genomic regions of low recombination.
      This study provides one of the first insights into genetic basis of hybrid female
      sterility in organisms with heterogametic females.

PMID- 29319913
TI  - What is your diagnosis? Inguinal mass in a dog.

PMID- 29319914
TI  - Aquablation therapy for symptomatic benign prostatic hyperplasia: a single-centre
      experience in 47 patients.
AB  - OBJECTIVE: To report procedure process improvements and confirm the preserved
      safety and short-term effectiveness of a second-generation Aquablation device for
      the treatment of lower urinary tract symptoms (LUTS) attributable to benign
      prostatic hyperplasia (BPH) in 47 consecutive patients at a single institution.
      PATIENTS AND METHODS: Aquablation was performed in 47 patients with symptomatic
      BPH at a single institution. Baseline, peri-operative and 3-month urinary
      function data were collected. RESULTS: The mean (range) patient age was 66 (50
      79) years, and transrectal ultrasonography-measured prostate volume was 48 (20
      118) mL. A median lobe was present in 25 patients (53%) and eight patients had
      catheter-dependent urinary retention. The mean (range) total procedure time was
      35 (13-128) min and the tissue resection time was 4 (1-10) min. Five Clavien
      Dindo grade I/II and five Clavien-Dindo grade III complications were recorded in
      eight patients. The mean (range) hospital stay was 3.1 (1-8) days and the mean
      (range) duration of urethral catheterization was 1.9 (1-11) days. The mean
      International Prostate Symptom Score (IPSS) decreased from 24.4 at baseline to 5
      at 3 months; IPSS quality-of-life score decreased from 4.5 to 0.3 points; peak
      urinary flow rate increased from 7.1 to 16.5 mL/s and post-void residual urine
      volume decreased from 119 to 43 mL (all P < 0.01). CONCLUSIONS: This study
      confirmed procedure process improvements resulting from system enhancements, with
      preservation of safety and effectiveness during use of a second-generation device
      for the treatment of LUTS attibutable to BPH in the largest single-institution
      study conducted to date.

PMID- 29319915
TI  - Enantioselective ultra high performance liquid and supercritical fluid
      chromatography: The race to the shortest chromatogram.
AB  - The ever-increasing need for enantiomerically pure chiral compounds has greatly
      expanded the number of enantioselective separation methods available for the
      precise and accurate measurements of the enantiomeric purity. The introduction of
      chiral stationary phases for liquid chromatography in the last decades has
      revolutionized the routine methods to determine enantiomeric purity of chiral
      drugs, agrochemicals, fragrances, and in general of organic and organometallic
      compounds. In recent years, additional efforts have been placed on faster,
      enantioselective analytical methods capable to fulfill the high throughput
      requirements of modern screening procedures. Efforts in this field, capitalizing
      on improved chromatographic particle technology and dedicated instrumentation,
      have led to highly efficient separations that are routinely completed on the
      seconds time scale. An overview of the recent achievements in the field of ultra
      high-resolution chromatography on column packed with chiral stationary phases,
      both based on sub-2 MUm fully porous and sub-3 MUm superficially porous
      particles, will be given, with an emphasis on very recent studies on ultrafast
      chiral separations.

PMID- 29319916
TI  - 1.0T MR-guided percutaneous coaxial cutting needle biopsy in pancreatic lesion
      diagnosis.
AB  - BACKGROUND: Pancreatic carcinoma is a common cause of cancer deaths worldwide.
      Biopsy is often required for the initial diagnosis of pancreatic masses. Biopsy
      can be performed endoscopically or percutaneously with computed tomography (CT)
      and ultrasound (US) guidance. MRI offers many inherent advantages over CT and US.
      PURPOSE/HYPOTHESIS: To prospectively evaluate the feasibility, accuracy, and
      safety of MRI-guided percutaneous coaxial cutting needle biopsy of pancreatic
      lesions using an open 1.0T high-field MR scanner. STUDY TYPE: Prospective.
      POPULATION: Thirty-one patients with 31 pancreatic lesions underwent MR-guided
      percutaneous coaxial cutting needle biopsy. FIELD STRENGTH/SEQUENCE: 1.0T T2 WI
      TSE PDW-aTSE T1 WI-TFE. ASSESSMENT: Final diagnosis was confirmed by surgery and
      clinical follow-up for at least 12 months. The accuracy, sensitivity, and
      specificity were calculated. Complications were recorded. STATISTICAL TESTS:
      There was no statistical analysis in this study. RESULTS: The procedure was
      technically successful and final biopsy samples were adequate for
      histopathological examination in all patients. Biopsy pathology revealed
      malignant pancreatic tumor in 25 patients (25/31, 80.6%), and benign pancreatic
      lesions were present in six patients (6/31, 19.4%). The final diagnosis was
      pancreatic malignancy in 27 patients and benign disease in four patients, which
      was confirmed by surgery and clinical follow-up. Two biopsy results were false
      negative. The diagnostic accuracy in biopsies was 93.5% (29 of 31). The
      sensitivity to detect a malignant disease was 92.6% (25 of 27), and the
      specificity was 100%. All patients tolerated the procedure well; minor
      peripancreatic hemorrhage was found in two patients after the procedure, and none
      had major complications either during or after the procedure. DATA CONCLUSION:
      MRI-guided percutaneous biopsy of pancreatic lesions using an open 1.0T high
      field scanner has high diagnostic accuracy, which is feasible and safe for use in
      clinical practice. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. MAGN.
      RESON. IMAGING 2018;48:382-388.

PMID- 29319917
TI  - Nerve-sparing radical cystectomy has a beneficial impact on urinary continence
      after orthotopic bladder substitution, which becomes even more apparent over
      time.
AB  - OBJECTIVE: To analyse urinary continence in long-term survivors after radical
      cystectomy (RC) and orthotopic bladder substitution (OBS) according to attempted
      nerve-sparing (NS) status. PATIENTS AND METHODS: We analysed 180 consecutive
      patients treated at our department between 1985 and 2007, who underwent RC with
      OBS, and survived >=10 years after RC. We stratified patients by attempted NS
      status and evaluated continence outcomes using descriptive statistics and Cox
      proportional hazards regression models. A secondary analysis evaluated erectile
      function as a quality control for attempted NS. RESULTS: The median
      (interquartile range [IQR]) age at RC was 62 (57-71) years. Of 180 patients,
      attempted NS status was none in 24 (13%), unilateral in 100 (56%), and bilateral
      in 56 (31%). After a median (IQR) follow-up of 169 (147-210) months, 160 (89%)
      patients were continent during daytime and 124 (69%) during night-time. In
      multivariable analysis, any degree of attempted NS was significantly associated
      with daytime continence (odds ratio [OR] 2.08, 95% confidence interval [CI] 1.05
      4.11; P = 0.04). Correspondingly, any attempted NS was significantly associated
      with night-time continence (OR 2.51, 95% CI 1.08-5.85; P = 0.03). Recovery of
      erectile function at 5 years was also significantly associated with attempted NS
      (P < 0.001). CONCLUSION: Nerve-sparing during RC and OBS was associated with
      better long-term continence outcomes. This becomes more apparent as the patients
      age with their OBS. We advocate a NS RC whenever an OBS is considered.

PMID- 29319918
TI  - Comparison of modified two-point dixon and chemical shift encoded MRI water-fat
      separation methods for fetal fat quantification.
AB  - BACKGROUND: Fetal fat is indicative of the energy balance within the fetus, which
      may be disrupted in pregnancy complications such as fetal growth restriction,
      macrosomia, and gestational diabetes. Water-fat separated MRI is a technique
      sensitive to tissue lipid content, measured as fat fraction (FF), and can be used
      to accurately measure fat volumes. Modified two-point Dixon and chemical shift
      encoded MRI (CSE-MRI) are water-fat separated MRI techniques that could be
      applied to imaging of fetal fat. Modified two-point Dixon has biases present that
      are corrected in CSE-MRI which may contribute to differences in the fat
      measurements. PURPOSE: To compare the measurement of fetal fat volume and FF by
      modified two-point Dixon and CSE-MRI. STUDY TYPE: Cross-sectional study for
      comparison of two MRI pulse sequences. POPULATION: Twenty-one pregnant women with
      singleton pregnancies. FIELD STRENGTH/SEQUENCE: 1.5T, modified two-point Dixon
      and CSE-MRI. ASSESSMENT: Manual segmentation of total fetal fat volume and mean
      FF from modified 2-point Dixon and CSE-MRI FF images. STATISTICAL TESTS:
      Reliability was assessed by calculating the intraclass correlation coefficient
      (ICC). Agreement was assessed using a one-sample t-test on the fat measurements
      difference values (modified two-point Dixon - CSE-MRI). The difference scores
      were tested against a value of 0, which would indicate that the measurements were
      identical. RESULTS: The fat volume and FF measured by modified two-point Dixon
      and CSE-MRI had excellent reliability, demonstrated by ICCs of 0.93 (P < 0.001)
      and 0.90 (P < 0.001), respectively. They were not in agreement, with CSE-MRI
      giving mean fat volumes 180 mL greater and mean FF 3.0% smaller than modified two
      point Dixon. DATA CONCLUSION: The reliability between modified two-point Dixon
      and CSE-MRI indicates that either technique can be used to compare fetal fat
      measurements in different participants, but they are not in agreement possibly
      due to uncorrected biases in modified two-point Dixon. LEVEL OF EVIDENCE: 4
      Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018.

PMID- 29319919
TI  - Outcomes and toxicities in patients with intermediate-risk prostate cancer
      treated with brachytherapy alone or brachytherapy and supplemental external beam
      radiation therapy.
AB  - OBJECTIVE: To evaluate the cancer control outcomes and long-term treatment
      related morbidity of brachytherapy as well as combination brachytherapy and
      external beam radiation therapy (EBRT) in patients with intermediate-risk
      prostate cancer. MATERIALS AND METHODS: A retrospective review was conducted in a
      prospectively collected database of patients with intermediate-risk prostate
      cancer who were treated either with brachytherapy or brachytherapy and EBRT, with
      or without androgen deprivation therapy (ADT), in the period 1990-2014. Urinary
      and erectile dysfunction symptoms were measured using the International Prostate
      Symptom Score (IPSS), the Mount Sinai erectile function scale and the Sexual
      Health Inventory for Men (SHIM). Cancer control endpoints included biochemical
      failure and development of distant metastases. All statistical analyses were
      carried out using the Statistical Package for Social Science (SPSS). Survival
      curves were calculated using Kaplan-Meier actuarial methods and compared using
      log-rank tests. Cox regression multivariate analyses were used to test the effect
      of multiple variables on treatment outcomes. RESULTS: A total of 902 patients
      were identified, with a median follow-up of 91 months. Of these, 390 received
      brachytherapy and 512 received combination therapy with EBRT. In patients with
      one intermediate-risk factor, the addition of EBRT did not significantly affect
      freedom from biochemical failure or distant metastases. Among patients with two
      or three intermediate-risk factors, added EBRT did not improve freedom from
      biochemical failure. Significant differences in late toxicity between patients
      treated with brachytherapy vs combination brachytherapy and EBRT were identified
      including urge incontinence (P < 0.001), haematuria (P < 0.001), dysuria (P <
      0.001), and change in quality-of-life IPSS (P = 0.002). These symptoms were
      reported by patients at any point during treatment follow-up. Analysis of
      patients who were potent before treatment using actuarial methods showed that
      patients receiving combination therapy more frequently experienced loss of
      potency, as measured by the Mount Sinai erectile function scale (P = 0.040).
      CONCLUSION: Brachytherapy monotherapy results in equal biochemical and distant
      control in both patients with one and more than one intermediate-risk features.
      While no significant benefit was shown, we believe that the addition of EBRT may
      prevent recurrence in patients with multiple intermediate-risk features and
      should be considered.

PMID- 29319920
TI  - Employee attitudes towards aggression in persons with dementia: Readiness for
      wider adoption of person-centered frameworks.
AB  - WHAT IS KNOWN ON THE SUBJECT: Person-centered care, as compared to standard
      approaches, is a widely accepted, evidence-based approach for managing aggressive
      behaviour in persons with dementia. The attitudes, beliefs and values of long
      term care and mental health nursing employees are important prerequisites to
      implementing person-centered practices. Research shows that nursing employees
      typically support person-centered approaches; however, less is known about the
      attitudes of non-nursing employee groups. WHAT THIS PAPER ADDS TO EXISTING
      KNOWLEDGE: Nurse managers and administrators tended to agree with person-centered
      approaches for managing aggression in dementia, suggesting some prerequisites are
      in place to support wider adoption of person-centered frameworks. Employees with
      more resident contact tended to support person-centered approaches the least,
      suggesting discipline-specific trainings may not be adequate for preparing
      frontline staff to use person-centered techniques. Attitudes towards aggressive
      behaviour may be especially varied and contradictory within certain employee
      groups, providing implications for facility-wide initiatives. IMPLICATIONS FOR
      PRACTICE: Person-centered values and practices should be monitored and reinforced
      across the organization. Person-centered trainings should be interdisciplinary in
      nature and focused on care areas, such as mealtime or bathing. Long-term care
      facilities should consider allowing nurse management and registered nurses to
      share the burden of direct resident care with frontline employees on a more
      regular basis. ABSTRACT: Introduction Implementing person-centered care requires
      shared attitudes, beliefs and values among all care employees. Existing research
      has failed to examine the attitudes of non-nursing employees. Aim This study
      examined attitudes towards aggression among nursing and non-nursing employees to
      address gaps in existing research and assess readiness for wider adoption of
      person-centered frameworks. Method The Management of Aggression in People with
      Dementia Attitude Questionnaire was used to survey attitudes of employees in
      Michigan-based nursing homes. Results Overall, employees preferred person
      centered over standard approaches. Job title was a significant predictor of
      paradigm support. Frontline employees were found to support person-centered
      attitudes the least. Wide-ranging responses were noted within employee groups.
      Discussion Job title may influence the degree to which an employee supports and
      utilizes person-centered approaches. Employees with the most contact with persons
      with dementia may be the least likely to implement person-centered approaches. In
      contrast to prior studies, years of experience was not a significant predictor of
      attitude towards aggressive behaviour. Wide-ranging responses indicate that
      employee attitudes are varied and complex. Implications Person-centered
      approaches should be trained within care areas rather than individual employee
      groups. Programs should be interdisciplinary and seek to establish a shared
      understanding of person-centered beliefs and values.

PMID- 29319921
TI  - Enantioselective and simultaneous determination of lactate and 3-hydroxybutyrate
      in human plasma and urine using a narrow-bore online two-dimensional high
      performance liquid chromatography system.
AB  - For the enantioselective and simultaneous analysis of lactate and 3
      hydroxybutyrate, a validated online two-dimensional high-performance liquid
      chromatography system using 4-nitro-7-piperazino-2,1,3-benzoxadiazole as a
      fluorescent derivatization reagent has been developed. For the reversed-phase
      separation in the first dimension, a Capcell Pak C18 ACR column (1.5 * 250 mm,
      particle size 3 MUm) was used, and the target fractions were isolated by their
      hydrophobicity. In the second dimension, a polysaccharide-coated enantioselective
      column, Chiralpak AD-H (2.0 * 250 mm, 5 MUm), was used. The system was validated
      by the calibration curve, intraday precision, interday precision, and accuracy
      using standards and real human samples, and satisfactory results were obtained.
      The present method was applied to human plasma and urine, and in the plasma,
      trace amounts of d-lactate (8.4 MUM) and l-3-hydroxybutyrate (1.0 MUM), besides
      high levels of l-lactate (860.9 MUM) and d-3-hydroxybutyrate (59.4 MUM), were
      successfully determined. In urine, trace levels of d-lactate (3.7 MUM), d-3
      hydroxybutyrate (2.3 MUM), and l-3-hydroxybutyrate (3.3 MUM) in addition to a
      relatively large amount of l-lactate (15.4 MUM) were observed. The present online
      two-dimensional high-performance liquid chromatography system is useful for the
      simultaneous determination of all the lactate and 3-hydroxybutyrate enantiomers
      in human physiological fluids, and further clinical applications are ongoing.

PMID- 29319922
TI  - The effect of timing of an immediate instillation of mitomycin C after
      transurethral resection in 941 patients with non-muscle-invasive bladder cancer.
AB  - OBJECTIVE: To investigate whether the timing of an immediate instillation of
      mitomycin C (on the day of transurethral resection of bladder tumour [TURBT] or 1
      day later) has an impact on time to recurrence of non-muscle-invasive bladder
      cancer (NMIBC). PATIENTS AND METHODS: All patients with NMIBC who were enrolled
      in a prospective trial between 1998 and 2003, and treated with an early mitomycin
      C instillation (on the day of TURBT or 1 day later), were selected. Statistical
      analysis was performed with Kaplan-Meier curves and multivariable Cox regression.
      RESULTS: Administering an instillation of mitomycin C on the day of TURBT or 1
      day later did not show a statistically significant difference in time to
      recurrence in a univariable model (log-rank P = 0.99). After correcting for the
      number of scheduled adjuvant instillations, no statistically significant
      difference could be detected either: hazard ratio 1.05 (95% confidence interval
      0.81-1.35, P = 0.74). CONCLUSION: These data do not support the hypothesis that a
      very early instillation (on the day of TURBT) of mitomycin C decreases the risk
      of recurrence as compared with an early instillation (1 day after TURBT).

PMID- 29319923
TI  - Attitudes towards mental health, mental health research and digital interventions
      by young adults with type 1 diabetes: A qualitative analysis.
AB  - BACKGROUND: Young people with type 1 diabetes are at increased risk of mental
      disorders. Whereas treatment need is high, difficulty recruiting young people
      with type 1 diabetes into psychosocial studies complicates development, testing
      and dissemination of these interventions. OBJECTIVE: Interviews with young adults
      with type 1 diabetes were conducted to examine attitudes towards mental health
      and mental health research, including barriers and motivators to participation in
      mental health studies and preferred sources of mental health support. The
      interviews were audio-taped, transcribed and evaluated via thematic analysis.
      SETTING AND PARTICIPANTS: Young adults with type 1 diabetes were recruited via
      social media channels of 3 advocacy organizations. A total of 31 young adults (26
      females and 5 males) with an average age of 22 years were interviewed between
      October 2015 and January 2016. RESULTS: Participants were largely unaware of
      their increased vulnerability to common mental health problems and knew little
      about mental health research. Major barriers to participation included perceived
      stigma and lifestyle issues and low levels of trust in researchers. Opportunities
      to connect with peers and help others were described as key motivators.
      Psychological distress was considered normal within the context of diabetes. A
      need for some level of human contact in receiving psychosocial support was
      expressed. DISCUSSION AND CONCLUSION: Findings provide valuable insights into the
      complex dynamics of engaging young adults with type 1 diabetes in mental health
      studies. Interviewees provided practical suggestions to assist investigation and
      delivery of psychosocial interventions for this vulnerable group.

PMID- 29319924
TI  - Myocardial oedema and congestive heart failure: one piece of the puzzle? Reply.

PMID- 29319925
TI  - Differences between serious and nonserious patient safety incidents in the
      largest hospital district in Finland.
AB  - OBJECTIVES: To determine if and in what ways serious patient safety incidents
      differ from nonserious patient safety incidents. METHODS: Statistical analysis
      was performed on patient safety incident reports that were reported in 2015 in
      Finland's largest hospital district (Helsinki and Uusimaa, HUS). Reports were
      divided into two groups: nonserious incidents and serious incidents. Differences
      between groups were studied from several types of categorically divided
      information. RESULTS: Of the total number of reports (15,863), 1% were serious
      incidents (175). Serious and nonserious incidents differed significantly from
      each other. Serious incidents concerning laboratory, imaging, or medical
      equipment were more common. On the other hand, incidents concerning medication,
      infusion, and blood transfusion were less frequent. In serious incidents, the
      proportion of doctors reporting was greater, and contributing factors were better
      recognized, the most common being working of procedures. CONCLUSIONS: In the
      future, special attention should be given to the particular aspects of serious
      patient safety incidents, such as safe use of medical equipment, training, and
      handling of procedures. Root cause analysis is an effective way to handle serious
      incidents and enables the prevention of their reoccurrence. However, a systematic
      follow-up of the root cause analysis should be developed.

PMID- 29319926
TI  - The role of lymph node dissection in the management of renal cell carcinoma: a
      systematic review and meta-analysis.
AB  - Our objective was to evaluate the role of retroperitoneal lymph node dissection
      (LND) in non-metastatic (M0) and metastatic (M1) renal cell carcinoma (RCC). We
      searched Medline, EMBASE, Web of Science and Scopus from database inception to 29
      August 2017 for studies of patients who underwent partial or radical nephrectomy
      for M0 or M1 RCC. Two investigators independently selected studies for inclusion.
      Risk of bias was assessed using the Newcastle-Ottawa scale, Cochrane
      Collaboration tool and National Heart, Lung and Blood Institute Quality
      Assessment Tool. Random effects meta-analysis was performed for all-cause
      mortality. The GRADE approach was used to characterize quality of evidence. A
      total of 51 unique studies were included in the qualitative systematic review.
      Risk of bias was low in 41/51 (80%) studies. LND was not associated with all
      cause mortality in either M0 (hazard ratio [HR] 1.02, 95% confidence interval
      [CI] 0.92-1.12; I2 = 0%; four studies), M1 (HR 1.04, 95% CI 0.83-1.29; I2 = 0%;
      two studies), or pooled M0 and M1 settings (HR 1.00, 95% CI 0.92-1.09; I2 = 0%;
      seven studies), with no statistically significant differences according to M
      stage subgroups (P = 0.50). In the three studies that examined M0 subgroups with
      a high risk of nodal metastasis, LND was not associated with improved oncological
      outcomes. Studies on the association of extent of LND with survival reported
      inconsistent results. Meanwhile, a small proportion of patients with pN1M0
      disease demonstrate durable long-term oncological control after surgery, with 10
      year cancer-specific survival of 21-31%. Nodal involvement is independently
      associated with adverse prognosis in both M0 and M1 settings. GRADE quality of
      evidence was moderate or low for the outcomes examined. Although LND yields
      independent prognostic information, the existing literature does not support a
      therapeutic benefit to LND in either M0 or M1 RCC. High-risk M0 patient groups
      warrant further study, as a subset of patients with isolated nodal metastases
      experience long-term survival after surgical resection.

PMID- 29319927
TI  - Which outcome measures should be used in stress urinary incontinence trials?
AB  - OBJECTIVE: To review measures used in recent randomised controlled trials (RCTs)
      evaluating stress urinary incontinence (SUI) treatments and to propose the most
      relevant outcome measure that should be included in future trials. MATERIALS AND
      METHODS: We identified RCTs for SUI interventions published between January 2015
      and July 2017. We listed the objective and subjective outcome measures used in
      eligible trials in the literature search. Using data from our RCT conducted from
      2013 to 2016 evaluating pulsed magnetic stimulation for SUI, we analysed the
      correlation between all measures. RESULTS: A total of 45 RCTs were included; 28
      (62%) involved surgical interventions. The most frequently used objective and
      subjective measures were the cough stress test and International Consultation on
      Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF),
      respectively. In all, 24 different validated questionnaires were administered in
      the 42 studies that used subjective outcome measure. Analyses of measures used in
      our trial showed that all measures were significantly correlated with each other
      except for pelvic floor muscle function. The ICIQ-UI SF showed the highest
      correlation coefficients (0.587-0.733) with all outcome measures. CONCLUSION: The
      outcome measures used in recent trials were inconsistent. The ICIQ-UI SF had the
      highest correlation with all measures in our trial; however, further studies
      evaluating correlation of measures in other patient cohorts are needed to
      corroborate our present results. We propose the use of ICIQ-UI SF, as the most
      relevant outcome measure, in future trials evaluating efficacy of SUI
      interventions.

PMID- 29319928
TI  - Low-dose-rate brachytherapy for prostate cancer: outcomes at >10 years of follow
      up.
AB  - OBJECTIVE: To examine biochemical control, survival, and late morbidity with
      definitive low-dose-rate brachytherapy (LDR-BT) for patients with prostate cancer
      surviving for >10 years after treatment. PATIENTS AND METHODS: We identified 757
      men with localised prostate cancer who underwent definitive LDR-BT in the period
      1990-2006 and were followed for >10 years at our institution. Biochemical failure
      free survival (BFFS), distant metastases-free survival (DMFS), prostate cancer
      specific survival (PCSS), and overall survival (OS) were selected as study
      endpoints. Survival was examined using the log-rank test, Kaplan-Meier method,
      and Cox regression modelling. Urinary, quality of life (QoL), and potency scores
      at baseline and last follow-up were recorded. RESULTS: The median follow-up was
      12.5 years (range, 10.1-21.8 years). At the time of analysis, 88.6% of patients
      were alive, 1.5% died from prostate cancer and 13.9% developed biochemical
      failure, with 82% of failures occurring in the first decade of follow-up.
      Overall, 2.3% developed distant metastases. On multivariate analyses, stage T3a
      T3b, prostate-specific antigen level of >20 ng/mL, intermediate- and high-risk
      disease predicted worse BFFS; whereas age >70 years at diagnosis and stage T3a
      T3b predicted worse OS. A total biologically effective dose of >=150 Gy and
      androgen-deprivation therapy were associated with improved BFFS, but not OS. The
      overall 17-year rates for BFFS, DMFS, PCSS, and OS were 79, 97, 97, and 72%,
      respectively. Respective 17-year BFFS rates for low-, intermediate- and high-risk
      patients were 86, 80, and 65% (P < 0.001), whereas OS rates for the same groups
      were 82, 73, and 60%, respectively (P = 0.09). Amongst those patients who were
      potent at baseline, 25% remained potent at the last follow-up. Urinary function
      and QoL were mainly unaffected. CONCLUSIONS: LDR-BT yields excellent survival
      rates, with a 17-year PCSS rate of 97%. In all, 18% of patients with biochemical
      relapse failed at >10 years after implantation, which justifies their continued
      follow-up.

PMID- 29319929
TI  - Interconversion of Molybdenum Imido and Amido Complexes by Proton-Coupled
      Electron Transfer.
AB  - Interconversion of the molybdenum amido [(Ph Tpy)(PPh2 Me)2 Mo(NHtBuAr)][BArF24 ]
      (Ph Tpy=4'-Ph-2,2',6',2"-terpyridine; tBuAr=4-tert-butyl-C6 H4 ; ArF24 =(C6 H3 
      3,5-(CF3 )2 )4 ) and imido [(Ph Tpy)(PPh2 Me)2 Mo(NtBuAr)][BArF24 ] complexes has
      been accomplished by proton-coupled electron transfer. The 2,4,6-tri-tert
      butylphenoxyl radical was used as an oxidant and the non-classical ammine complex
      [(Ph Tpy)(PPh2 Me)2 Mo(NH3 )][BArF24 ] as the reductant. The N-H bond
      dissociation free energy (BDFE) of the amido N-H bond formed and cleaved in the
      sequence was experimentally bracketed between 45.8 and 52.3 kcal mol-1 , in
      agreement with a DFT-computed value of 48 kcal mol-1 . The N-H BDFE in
      combination with electrochemical data eliminate proton transfer as the first step
      in the N-H bond-forming sequence and favor initial electron transfer or concerted
      pathways.

PMID- 29319931
TI  - Metaproteomics of Colonic Microbiota Unveils Discrete Protein Functions among
      Colitic Mice and Control Groups.
AB  - Metaproteomics can greatly assist established high-throughput sequencing
      methodologies to provide systems biological insights into the alterations of
      microbial protein functionalities correlated with disease-associated dysbiosis of
      the intestinal microbiota. Here, the authors utilize the well-characterized
      murine T cell transfer model of colitis to find specific changes within the
      intestinal luminal proteome associated with inflammation. MS proteomic analysis
      of colonic samples permitted the identification of ~10 000-12 000 unique peptides
      that corresponded to 5610 protein clusters identified across three groups,
      including the colitic Rag1-/- T cell recipients, isogenic Rag1-/- controls, and
      wild-type mice. The authors demonstrate that the colitic mice exhibited a
      significant increase in Proteobacteria and Verrucomicrobia and show that such
      alterations in the microbial communities contributed to the enrichment of
      specific proteins with transcription and translation gene ontology terms. In
      combination with 16S sequencing, the authors' metaproteomics-based microbiome
      studies provide a foundation for assessing alterations in intestinal luminal
      protein functionalities in a robust and well-characterized mouse model of
      colitis, and set the stage for future studies to further explore the functional
      mechanisms of altered protein functionalities associated with dysbiosis and
      inflammation.

PMID- 29319932
TI  - Pharmacokinetics, Safety, and Tolerability of Tedizolid Phosphate in Elderly
      Subjects.
AB  - Tedizolid phosphate is approved for the treatment of acute bacterial skin and
      skin structure infections in adults. We evaluated the pharmacokinetics of
      tedizolid in elderly subjects to guide dosing recommendations. In an open-label
      phase 1 study (ClinicalTrials.gov identifier NCT01496677), 14 elderly (>=65
      years) and 14 younger control (18-45 years) subjects each received a single oral
      dose of tedizolid phosphate 200 mg. Blood samples were collected before dose and
      more than 72 hours after dose. The pharmacokinetic parameters of tedizolid after
      a single dose were similar in both age groups. Geometric mean ratios
      (elderly/younger controls) and corresponding 90% confidence intervals were
      maximum observed plasma concentration (Cmax ), 1.091 (0.917-1.297); AUC from time
      0 extrapolated to infinity (AUC0-infinity ), 1.132 (0.954-1.343). Tedizolid
      plasma exposure was similar in elderly and younger control subjects. The findings
      indicated that after intravenous or oral administration of tedizolid phosphate
      200 mg once daily, no dose adjustment was warranted in elderly subjects to
      achieve therapeutic levels.

PMID- 29319934
TI  - Identification and functional characterization of type II toxin/antitoxin systems
      in Aggregatibacter actinomycetemcomitans.
AB  - Type II toxin/antitoxin (TA) systems contribute to the formation of persister
      cells and biofilm formation for many organisms. Aggregatibacter
      actinomycetemcomitans thrives in the complex oral microbial community subjected
      to continual environmental flux. Little is known regarding the presence and
      function of type II TA systems in this organism or their contribution to
      adaptation and persistence in the biofilm. We identified 11 TA systems that are
      conserved across all seven serotypes of A. actinomycetemcomitans and represent
      the RelBE, MazEF and HipAB families of type II TA systems. The systems
      selectively responded to various environmental conditions that exist in the oral
      cavity. Two putative RelBE-like TA systems, D11S_1194-1195 and D11S_1718-1719
      were induced in response to low pH and deletion of D11S_1718-1719 significantly
      reduced metabolic activity of stationary phase A. actinomycetemcomitans cells
      upon prolonged exposure to acidic conditions. The deletion mutant also exhibited
      reduced biofilm biomass when cultured under acidic conditions. The D11S_1194 and
      D11S_1718 toxin proteins inhibited in vitro translation of dihydrofolate
      reductase (DHFR) and degraded ribosome-associated, but not free, MS2 virus RNA.
      In contrast, the corresponding antitoxins (D11S_1195 and D11S_1719), or equimolar
      mixtures of toxin and antitoxin, had no effect on DHFR production or RNA
      degradation. Together, these results suggest that D11S_1194-1195 and D11S_1718
      1719 are RelBE-like type II TA systems that are activated under acidic conditions
      and may function to cleave ribosome-associated mRNA to inhibit translation in A.
      actinomycetemcomitans. In vivo, these systems may facilitate A.
      actinomycetemcomitans adaptation and persistence in acidic local environments in
      the dental biofilm.

PMID- 29319935
TI  - Clinical Bioavailability of the Novel BACE1 Inhibitor Lanabecestat (AZD3293):
      Assessment of Tablet Formulations Versus an Oral Solution and the Impact of
      Gastric pH on Pharmacokinetics.
AB  - The relative bioavailability of lanabecestat administered as 2 tablet
      formulations versus an oral solution was investigated. This phase 1 single
      center, open-label, randomized, 3-period crossover study involved healthy male
      and nonfertile female subjects aged 18-55 years (NCT02039180). Subjects received
      a single 50-mg lanabecestat dose as solution, tablet A, or tablet B on day 1 of
      each crossover period; 14 of 16 subjects completed the study. Relative
      bioavailability based on plasma lanabecestat AUC0-infinity (area under the plasma
      drug concentration-time curve from zero to infinity) geometric mean ratio versus
      oral solution (primary variable) was: tablet A, 1.052 (90% confidence interval
      [CI], 1.001-1.106); tablet B, 1.040 (0.989-1.093). These 90%CIs for geometric
      mean ratios are within accepted standard bioequivalence boundaries for all other
      pharmacokinetic (PK) parameters for both lanabecestat and metabolite
      (AZ13569724). All 3 formulations had similar plasma lanabecestat concentration
      time profiles. Six adverse events were reported by 6 subjects (37.5%, all mild).
      GastroPlus modeling predicted a negligible impact of gastric pH changes on
      systemic PK (up to pH 7.4). Both tablet formulations fall within standard
      accepted bioequivalence criteria versus the oral solution. A single 50-mg
      lanabecestat dose was well tolerated as a solution or tablet formulation in this
      population.

PMID- 29319936
TI  - Submucosal gland mucus strand velocity is decreased in chronic rhinosinusitis.
AB  - BACKGROUND: Chronic rhinosinusitis (CRS) may be initiated by innately impaired
      host defense mechanisms that predispose the upper airways to infection. Recent
      evidence suggests tethering of submucosal gland mucus strands represents an
      inciting event within cystic fibrosis (CF) airways, occurring prior to onset of
      chronic infection. Submucosal gland hypertrophy and defective mucociliary
      clearance (MCC) are present in actively inflamed sinuses, but mucus strand
      velocity may also be affected as a secondary event, further contributing to
      chronic disease. The objective of this study is to assess whether mucus strand
      velocity is decreased in patients with CRS. METHODS: Mucosal explants from
      patients with and without CRS were submerged in Ringer's solution mixed with
      fluorescent nanospheres. Methacholine was then added, and videos demonstrating
      strand growth and detachment were generated from a time-lapse of Z-stack images
      using a multiphoton confocal microscope. Dynamic mucus strands were identified
      and individual velocities quantified with the MTrackJ plug-in of ImageJ. RESULTS:
      Fifteen patients met criteria for ex vivo analysis of mucus strand velocities
      (CRS, n = 9 vs controls, n = 6). Mucus strands were recorded (pixels/second)
      streaming from the submucosal gland openings. Average mucus strand velocities
      were significantly decreased in patients with CRS (1.53 +/- 0.67 vs controls,
      4.86 +/- 1.68 pixels/second; p < 0.001). CONCLUSION: This study is the first to
      report evidence of abnormal mucus strand velocity from submucosal glands in
      diseased sinonasal mucosa. Future pharmacologic studies targeting this critical
      component of MCC are warranted.

PMID- 29319937
TI  - Medical Devices; Clinical Chemistry and Clinical Toxicology Devices;
      Classification of the Reagents for Molecular Diagnostic Instrument Test Systems.
      Final order.
AB  - The Food and Drug Administration (FDA or we) is classifying the reagents for
      molecular diagnostic instrument test systems into class I (general controls). We
      are taking this action because we have determined that classifying the device
      into class I (general controls) will provide a reasonable assurance of safety and
      effectiveness of the device. We believe this action will also enhance patients'
      access to beneficial innovative devices, in part by reducing regulatory burdens.

PMID- 29319938
TI  - Medical Devices; Hematology and Pathology Devices; Classification of the Flow
      Cytometric Test System for Hematopoietic Neoplasms. Final order.
AB  - The Food and Drug Administration (FDA or we) is classifying the flow cytometric
      test system for hematopoietic neoplasms into class II (special controls). The
      special controls that apply to the device type are identified in this order and
      will be part of the codified language for the flow cytometric test system for
      hematopoietic neoplasms' classification. We are taking this action because we
      have determined that classifying the device into class II (special controls) will
      provide a reasonable assurance of safety and effectiveness of the device. We
      believe this action will also enhance patients' access to beneficial innovative
      devices, in part by reducing regulatory burdens.

PMID- 29319939
TI  - Medical Devices; Neurological Devices; Classification of the Computerized
      Behavioral Therapy Device for Psychiatric Disorders. Final order.
AB  - The Food and Drug Administration (FDA or we) is classifying the computerized
      behavioral therapy device for psychiatric disorders into class II (special
      controls). The special controls that apply to the device type are identified in
      this order and will be part of the codified language for the computerized
      behavioral therapy device for psychiatric disorders' classification. We are
      taking this action because we have determined that classifying the device into
      class II (special controls) will provide a reasonable assurance of safety and
      effectiveness of the device. We believe this action will also enhance patients'
      access to beneficial innovative devices, in part by reducing regulatory burdens.

PMID- 29319940
TI  - Medical Devices; Neurological Devices; Classification of the External Vagal Nerve
      Stimulator for Headache. Final order.
AB  - The Food and Drug Administration (FDA or we) is classifying the external vagal
      nerve stimulator for headache into class II (special controls). The special
      controls that apply to the device type are identified in this order and will be
      part of the codified language for the external vagal nerve stimulator for
      headache's classification. We are taking this action because we have determined
      that classifying the device into class II (special controls) will provide a
      reasonable assurance of safety and effectiveness of the device. We believe this
      action will also enhance patients' access to beneficial innovative devices, in
      part by reducing regulatory burdens.

PMID- 29319941
TI  - Medical Devices; Radiology Devices; Classification of the Rectal Balloon for
      Prostate Immobilization. Final order.
AB  - The Food and Drug Administration (FDA or we) is classifying the rectal balloon
      for prostate immobilization into class II (special controls). The special
      controls that apply to the device type are identified in this order and will be
      part of the codified language for the rectal balloon for prostate
      immobilization's classification. We are taking this action because we have
      determined that classifying the device into class II (special controls) will
      provide a reasonable assurance of safety and effectiveness of the device. We
      believe this action will also enhance patients' access to beneficial innovative
      devices, in part by reducing regulatory burdens.

PMID- 29319942
TI  - Medical Devices; Obstetrical and Gynecological Devices; Classification of the
      Pressure Wedge for the Reduction of Cesarean Delivery. Final order.
AB  - The Food and Drug Administration (FDA or we) is classifying the pressure wedge
      for the reduction of cesarean delivery into class II (special controls). The
      special controls that apply to the device type are identified in this order and
      will be part of the codified language for the pressure wedge for the reduction of
      cesarean delivery's classification. We are taking this action because we have
      determined that classifying the device into class II (special controls) will
      provide a reasonable assurance of safety and effectiveness of the device. We
      believe this action will also enhance patients' access to beneficial innovative
      devices, in part by reducing regulatory burdens.

PMID- 29319943
TI  - TRICARE; Reimbursement of Long Term Care Hospitals and Inpatient Rehabilitation
      Facilities. Final rule.
AB  - This final rule establishes reimbursement rates for Long Term Care Hospitals
      (LTCHs) and Inpatient Rehabilitation Facilities (IRFs) in accordance with the
      statutory requirement that TRICARE inpatient care "payments shall be determined
      to the extent practicable in accordance with the same reimbursement rules as
      apply to payments to providers of services of the same type under Medicare." This
      final rule adopts Medicare's reimbursement methodologies for inpatient services
      provided by LTCHs and IRFs. Each reimbursement methodology will be phased in over
      a 3-year period. This final rule also removes the definitions for "hospital, long
      term (tuberculosis, chronic care, or rehabilitation)" and "long-term hospital
      care," and creates separate definitions for "Long Term Care Hospital" and
      "Inpatient Rehabilitation Facility" adopting Centers for Medicare & Medicaid
      Services (CMS) classification criteria. This final rule also includes authority
      for a year-end, discretionary General Temporary Military Contingency Payment
      Adjustment (GTMCPA) for inpatient services in TRICARE network IRFs when deemed
      essential to meet military contingency requirements.

PMID- 29319944
TI  - Medical Devices; Hematology and Pathology Devices; Classification of the Whole
      Slide Imaging System. Final order.
AB  - The Food and Drug Administration (FDA or we) is classifying the whole slide
      imaging system into class II (special controls). The special controls that apply
      to the device type are identified in this order and will be part of the codified
      language for the whole slide imaging system's classification. We are taking this
      action because we have determined that classifying the device into class II
      (special controls) will provide a reasonable assurance of safety and
      effectiveness of the device. We believe this action will also enhance patients'
      access to beneficial innovative devices, in part by reducing regulatory burdens.

PMID- 29319945
TI  - Medical Devices; General and Plastic Surgery Devices; Classification of the
      Irrigating Wound Retractor Device. Final order.
AB  - The Food and Drug Administration (FDA or we) is classifying the irrigating wound
      retractor device into class II (special controls). The special controls that
      apply to the device type are identified in this order and will be part of the
      codified language for the irrigating wound retractor device's classification. We
      are taking this action because we have determined that classifying the device
      into class II (special controls) will provide a reasonable assurance of safety
      and effectiveness of the device. We believe this action will also enhance
      patients' access to beneficial innovative devices, in part by reducing regulatory
      burdens.

PMID- 29319946
TI  - Medical Devices; Hematology and Pathology Devices; Classification of a Cervical
      Intraepithelial Neoplasia Test System. Final order.
AB  - The Food and Drug Administration (FDA or we) is classifying the cervical
      intraepithelial neoplasia (CIN) test system into class II (special controls). The
      special controls that apply to the device type are identified in this order and
      will be part of the codified language for the CIN test system's classification.
      We are taking this action because we have determined that classifying the device
      into class II (special controls) will provide a reasonable assurance of safety
      and effectiveness of the device. We believe this action will also enhance
      patients' access to beneficial innovative devices, in part by reducing regulatory
      burdens.

PMID- 29319947
TI  - Schedules of Controlled Substances: Temporary Placement of Cyclopropyl Fentanyl
      in Schedule I. Temporary amendment; temporary scheduling order.
AB  - The Administrator of the Drug Enforcement Administration is  issuing this
      temporary scheduling order to schedule the synthetic opioid, -(1
      phenethylpiperidin-4-yl)-N-phenylcyclopropanecarboxamide  (cyclopropyl fentanyl),
      and its isomers, esters, ethers, salts, and salts of isomers, esters, and ethers
      in schedule I. This action is based on a finding by the Administrator that the
      placement of cyclopropyl fentanyl in schedule I of the Controlled Substances Act
      is necessary to avoid an imminent hazard to the public safety. As a result of
      this order, the regulatory controls and administrative, civil, and criminal
      sanctions applicable to schedule I controlled substances will be imposed on
      persons who handle (manufacture, distribute, reverse distribute, import, export,
      engage in research, conduct instructional activities or chemical analysis, or
      possess), or propose to handle, cyclopropyl fentanyl.

PMID- 29320138
TI  - Medical Devices; Radiology Devices; Classification of the Absorbable Perirectal
      Spacer. Final order.
AB  - The Food and Drug Administration (FDA or we) is classifying the absorbable
      perirectal spacer into class II (special controls). The special controls that
      apply to the device type are identified in this order and will be part of the
      codified language for the absorbable perirectal spacer's classification. We are
      taking this action because we have determined that classifying the device into
      class II (special controls) will provide a reasonable assurance of safety and
      effectiveness of the device. We believe this action will also enhance patients'
      access to beneficial innovative devices, in part by reducing regulatory burdens.

PMID- 29320139
TI  - Reimbursement for Emergency Treatment. Interim final rule.
AB  - The Department of Veterans Affairs (VA) revises its regulations concerning
      payment or reimbursement for emergency treatment for non-service-connected
      conditions at non-VA facilities to implement the requirements of a recent court
      decision. Specifically, this rulemaking expands eligibility for payment or
      reimbursement to include veterans who receive partial payment from a health-plan
      contract for non-VA emergency treatment and establishes a corresponding
      reimbursement methodology. This rulemaking also expands the eligibility criteria
      for veterans to receive payment or reimbursement for emergency transportation
      associated with the emergency treatment, in order to ensure that veterans are
      adequately covered when emergency transportation is a necessary part of their non
      VA emergency treatment.

PMID- 29320140
TI  - Using Community Partnerships to Integrate Health and Social Services for High
      Need, High-Cost Patients.
AB  - Issue: Our health care and social services delivery systems are not well-equipped
      to effectively manage patients with multiple chronic diseases and complex social
      needs such as food, housing, or substance abuse services. Community-level efforts
      have emerged across the nation to integrate the activities of disparate social
      service organizations with local health care delivery systems. Evidence on the
      experiences and outcomes of these programs is emerging, and there is much to
      learn about their approaches and challenges. Goal: Profile and classify
      burgeoning initiatives, understand common challenges, and surface solutions to
      address those challenges. Methods: Mixed-methods approach, including literature
      search, surveys, semistructured interviews with program leaders, and consultation
      with expert panels. Findings and Conclusions: We categorized cross-sector
      community partnerships in four dimensions. We also identified five common
      challenges: inadequate strategies to sustain cost-savings, improvement, and
      funding; lack of accurate and timely measurement of return on investment; lack of
      mechanisms to share potential savings between health care and social services
      providers; lack of expertise to integrate multiple data sources during health
      care or social services provision; and lack of a cross-sector workflow evidence
      base.

PMID- 29320141
TI  - Global Burden of Rheumatic Heart Disease.

PMID- 29320142
TI  - World suicide prevention day.

PMID- 29320143
TI  - Assessment and self-assessment of the pharmacists' competencies using the global
      competency framework (GbCF) in Serbia.
AB  - Background/Aim: Pharmacists' competence represents a dynamic framework of
      knowledge, skills and abilities to carry out tasks, and it reflects on improving
      the quality of life and on patients' health. One of the documents for the
      Evaluation and Competency Development of Pharmacists is the Global Competency
      Framework (GbCF). The aim of this study was to implement the GBCF document into
      Serbian pharmacies, to perform assessment and self assessment of the
      competencies. Methods: The assessment and self-assessment of pharmacists'
      competencies were performed during the period 2012-13 year in eight community
      pharmacy chains, in seven cities in Serbia. For assessment and self-assessment of
      pharmacists competencies the GbCF model was applied, which was adjusted to
      pharmaceutical practice and legislation in Serbia. External assessment was
      conducted by teams of pharmacists using the structured observation of the work of
      pharmacists during regular working hours. Evaluated pharmacists filled out the
      questionnaire about demographic indicators about the pharmacist and the pharmacy
      where they work. Results: A total of 123 pharmacists were evaluated. Pharmacists'
      Professional Competency Cluster (KK1) had the lowest score (average value 2.98),
      while the cluster Management and Organizational Competency (KK2) had the highest
      score (average value 3.15). The competence Recognition of the Diagnosis and
      Patient Counseling (K8), which belonged to the cluster KK1, had the lowest score
      (average value for assessment and self-assessment were 2.09, and 2.34,
      respectively) among the all evaluated competencies. Conclusion: GbCF might be
      considered as an instrument for the competencies' evaluation/selfevaluation and
      their improvement, accordingly.

PMID- 29320144
TI  - Translation and validation of the Croatian version of the Oral Impacts on Daily
      Performances (OIDP) scale.
AB  - Background/Aim: Among numerous sociodental indicators the Oral Impacts on Daily
      Performance (OIPD) is one of the most broadly applied. The aim of this study was
      to develop and test psychometric properties of a Croatian version of OIDP scale.
      Methods: The OIDP instrument was translated from English to Croatian in a forward
      backward method. The Croatian version was tested for reliability, construct
      validity and responsiveness on a sample of 702 participants (255 men), aged 18-86
      years. Results: Internal consistency of Croatian version of the OIDP was
      acceptable (alpha = 0.80) and 69.4% of the examinees had oral impacts relating to
      one or several performances. The most frequently affected performance was eating
      (53.7%). The test-retest reliability was high (r = 0.99; 95% CI: 0.97-0.99), the
      mean difference between the OIDP summary scores in two-week interval was not
      statistically significant. In construct validity testing there was statistically
      significant correlation between OIDP and self-assessed general and oral health,
      somatisation, depression and Oral Health Impact Profile ranging from 0.157 to
      0.516. Responsiveness was confirmed by a significant reduction of oral impacts on
      daily performances in subjects before and after treatment of acute dental pain (p
      < 0.001). Conclusion: The Croatian OIDP index showed good psychometric properties
      in terms of construct validity, internal consistency, test-retest reliability and
      responsiveness confirming its appropriateness for use among Croatian population.

PMID- 29320145
TI  - Prevalence of Borrelia burgdorferi sensu lato in Ixodes ricinus ticks and
      assessment of entomological risk index at localities in Belgrade.
AB  - Background/Aim: The first case of human Lyme borreliosis (LB) in Serbia was
      recorded in 1987. The number of reported LB cases has increased in the past
      decade. The aim of this study was to estimate the density of Ixodes ricinus (I.
      ricinus) ticks, the prevalence of Borrelia burgdorferi sensu lato (B.
      burgdorferi) in them, and entomological risk index (ERI) at 19 Belgrade
      localities which were grouped into three categories (forests, parkforests,
      parks). The values of ERI were compared with the number of tick bites in humans.
      Methods: Ticks were collected monthly by using the flag hours method and the
      infection rate was determined by using dark field microscopy. The ERI value was
      calculated for each locality where the ticks were collected. The related data
      about tick bites was obtained from the patient protocol of the Institute of
      Epidemiology, Military Medical Academy, Belgrade. Results: The total number of
      collected ticks, the number of nymphs and the infection rates of the nymphs were
      significantly higher in forests (p < 0.05) than park-forests and parks.
      Statistically, the ERI value was significantly higher in forests than parks of
      Belgrade (chi2 = 7.78, p < 0.01). In March and July, the ERI value was also
      significantly higher in forests, than park-forests (p < 0.01) and parks (p <
      0.01). May was the month with the highest ERI value in each ecological category
      (forests p < 0.05; park-forests p < 0.01; parks p < 0.001). However, the number
      of tick bites in humans did not correlate with ERI values. Conclusion: The
      obtained results indicate that the risk of tick bite and human exposure to B.
      burgdorferi sensu lato is present at all selected localities in Belgrade. For a
      more comprehensive Lyme disease risk assessment the method of entomological risk
      index assessment should be combined with other methods, taking into consideration
      all tick stages and the behaviour and habits of people who may get infected B.
      burgdorferi sensu lato.

PMID- 29320146
TI  - Upper extremity function and quality of life in patients with breast cancer
      related lymphedema.
AB  - Background/Aim: Upper limb lymphedema is one of the most frequent chronic
      complications after breast cancer treatment with a significant impact on the
      upper extremity function and quality of life (QoL). The aim of this study was to
      estimate health-related quality of life (HRQoL) in patients with breast-cancer
      related lymphedema and its correlation with upper limb function and the size of
      edema. Methods: The cross-sectional study included 54 breast-cancer-related
      lymphedema patients. The quality of life was evaluated by the Short Form 36-Item
      Health Survey (SF-36). Upper limb function was assessed by the Quick Disability
      of the Arm, Shoulder and Hand questionnaire (Quick DASH). The size of lymphedema
      was determined by the arm circumference. Results: The higher HRQoL score was
      assessed for mental health (47.0 +/- 12.2) than for physical one (42.2 +/- 7.5).
      The highest values of SF-36 were found in the domains of Mental Health (67.7 +/-
      22.9) and Social Function (70.1 +/- 23.1). The lowest scores were registered in
      the domains of Role Physical (46.9 +/- 39.1) and General Health (49.3 +/- 20.1).
      Upper extremity function statistically significantly correlated with the domains
      Role Physical, Bodily Pain and Physical Composite Summary and also, with the
      domain Role Emotional (p < 0.01). There was no statistically significant
      correlation between size of lymphedema and tested domains of quality of life (p >
      0.05). Conclusions: Physical disability in patients with breast cancer-related
      lymphedema influences quality of life more than mental health. Upper limb
      function has a significant impact on quality of life, not only on the physical,
      but also on the mental component. The presence of breast-cancer-related
      lymphedema certainly affects upper limb function and quality of life, but in this
      study no significant correlation between the size of edema and quality of life
      was found.

PMID- 29320147
TI  - Upper extremity function and quality of life in patients with breast cancer
      related lymphedema.
AB  - Background/Aim: Exposed to increasing needs of users for better and faster
      services, more medications and innovative health technologies, managers of
      healthcare services in the public sector need motivation, permanent updating of
      information and constant personal development. The aim of this paper was to
      evaluate, on the basis of experienced healthcare managers, the impact of their
      motivation, selected character traits, managerial skills and formal education in
      management on healthcare facilities performances in the public sector. Methods:
      For the purposes of this study, 97 experienced managers from public hospitals and
      primary health centers in Serbia answered to 30 questions on the motivation of
      managers, essential skills for successful management and formal education in
      management in health facilities. The obtained data about their motivation,
      governing experience, personal skills and formal education in management were
      systematized and processed by the Statistical Package for Social Sciences (SPSS).
      Healthcare facilities performances were expressed by the healthcare facilities
      ranks in the official annual rankings according to the quality improvement,
      conducted by the Institute of Public Health of Serbia. Pearson's or Spearman's
      correlation coefficients were used for proving the potential impact of selected
      factors on performances of healthcare facilities. Results: This study confirmed
      the association between the healthcare facilities ranks and managers' abilities
      to organize the working process (t = -2.453; p = 0.018); expressed high managers'
      motivation (rhoS = 0.206; p = 0.048) and the length of governing experience (r = 
      0.198; p = 0.043). Within a 3-year follow-up, this study also confirmed a
      positive correlation between annual ranks of healthcare facilities and managers
      quality management courses (rhoS = -0.238; p = 0.017) and managers education in
      human resources management (rhoS = -0.234; p = 0.027). Conclusion: In addition to
      management education, permanent personal development and higher motivation of
      managers have positive influence on healthcare performances.

PMID- 29320154
TI  - High-Precision Photothermal Ablation Using Biocompatible Palladium Nanoparticles
      and Laser Scanning Microscopy.
AB  - Herein, we report a straightforward method for the scalable preparation of Pd
      nanoparticles (Pd-NPs) with reduced inherent cytotoxicity and high photothermal
      conversion capacity. These Pd-NPs are rapidly taken up by cells and able to kill
      labeled cancer cells upon short exposure to near-infrared (NIR) light. Following
      cell treatment with Pd-NPs, ablated areas were patterned with high precision by
      laser scanning microscopy, allowing one to perform cell migration assays with
      unprecedented accuracy. Using coherent Raman microscopy, cells containing Pd-NPs
      were simultaneously ablated and imaged. This novel methodology was combined with
      intravital imaging to mediate microablation of cancerous tissue in tumor
      xenografts in mice.

PMID- 29320155
TI  - Transparent and Waterproof Ionic Liquid-Based Fibers for Highly Durable
      Multifunctional Sensors and Strain-Insensitive Stretchable Conductors.
AB  - Ionic liquids (ILs) are regarded as ideal components in the next generation of
      strain sensors because their ultralow modulus can commendably circumvent or
      manage the mechanical mismatch in traditional strain sensors. In addition to
      strain sensors, stretchable conductors with a strain-insensitive conductance are
      also indispensable in artificial systems for connecting and transporting
      electrons, similar to the function of blood vessels in the human body. In this
      work, two types of ILs-based conductive fibers were fabricated by developing
      hollow fibers with specific microscale channels, which were then filled with ILs.
      Typically, the ILs-based fiber with straight microchannels exhibited a high
      strain sensitivity and simultaneously rapid responses to strain, pressure, and
      temperature. The other ILs-based fiber with helical microchannels exhibited a
      good strain-isolate conductance under strain. Due to the high transparency of ILs
      along with the sealing process, the as-prepared ILs-based fibers are both highly
      transparent and waterproof. More importantly, owing to the low modulus of ILs and
      the core-shell structure, both conductive fiber prototypes demonstrated a high
      durability (>10 000 times) and a long-term stability (>4 months). Ultimately, the
      ILs-based fibrous sensors were successfully woven into gloves, flaunting the
      ability to detect human breathing patterns, sign language, hand gestures, and arm
      motions. The ILs-based strain-insensitive fibers were successfully applied in
      stretchable wires as well.

PMID- 29320156
TI  - Highly Stable Copper(I)-Based Metal-Organic Framework Assembled with
      Resorcin[4]arene and Polyoxometalate for Efficient Heterogeneous Catalysis of
      Azide-Alkyne "Click" Reaction.
AB  - A new highly stable copper(I)-based metal-organic framework (MOF), namely,
      [CuI4(SiW12O40)(L)].6H2O.2DMF (1), was synthesized by incorporating Keggin-type
      polyoxometalate (POM) anions and a functionalized wheel-like resorcin[4]arene
      based ligand (L) under sovothermal condition. 1 exhibits a charming 3D
      supramolecular architecture sandwiched by the POM anions. Noticeably, 1 has
      exceptional chemical stability, especially in organic solvents or aqueous
      solutions with a wide range of pH values. Considering the catalytically active
      Cu(I) sites in 1, the azide-alkyne cycloaddition (AAC) reaction was studied by
      employing 1 as the heterogeneous catalyst. Most strikingly, 1 exhibits excellent
      catalytic activity as well as recyclability for the AAC reaction.

PMID- 29320157
TI  - Superhydrophobic Microporous Substrates via Photocuring: Coupling Optical Pattern
      Formation to Phase Separation for Process-Tunable Pore Architectures.
AB  - We present a new approach to synthesize microporous surfaces through the
      combination of photopolymerization-induced phase separation and light pattern
      formation in photopolymer-solvent mixtures. The mixtures are irradiated with a
      wide-area light pattern consisting of high and low intensity regions. This light
      pattern undergoes self-focusing and filamentation, thereby preserving its spatial
      profile through the mixture. Over the course of irradiation, the mixture
      undergoes phase separation, with the polymer and solvent located in the bright
      and dark regions of the light profile, respectively, to produce a binary phase
      morphology with a congruent arrangement as the optical pattern. A congruently
      arranged microporous structure is attained upon solvent removal. The microporous
      surface structure can be varied by changing the irradiating light profile via
      photomask design. The porous architecture can be further tuned through the
      relative weight fractions of photopolymer and solvent in the mixture, resulting
      in porosities ranging from those with discrete and uniform pore sizes to
      hierarchical pore distributions. All surfaces become superhydrophobic (water
      contact angles >150 degrees ) when spray-coated with a thin layer of
      polytetrafluoroethylene nanoparticles. The water contact angles can be enhanced
      by changing the surface porosity via the processing conditions. This is a
      scalable and tunable approach to precisely control microporous surface structure
      in thin films to create functional surfaces and antiwetting coatings.

PMID- 29320158
TI  - Coordination-Mediated Synthesis of Purification-Free Bivalent 99mTc-Labeled
      Probes for in Vivo Imaging of Saturable System.
AB  - In the synthesis of technetium-99m (99mTc) labeled target-specific ligands, the
      presence of a large excess of unlabeled ligands over 99mTc in the injectate
      hinders target accumulation of 99mTc-labeled ligands by competing for target
      molecules. To circumvent the problem, we recently developed a concept of the
      metal coordination-mediated multivalency, and proved the concept with a 99mTc
      labeled trivalent compound [99mTc(CO)3(CN-RGD)3]+. In this study, D-penicillamine
      (Pen) was selected as a chelating molecule and a cyclic RGDfK peptide was
      conjugated to Pen via a hexanoic linkage (Pen-Ahx-c(RGDfK)). 99mTc complexation
      reaction, and the stability, integrin alphavbeta3 binding affinity, and
      biodistribution of the 99mTc-labeled probe were investigated to evaluate the
      applicability of the concept to bivalent probes. 99mTc-[Pen-Ahx-c(RGDfK)]2 was
      obtained over 95% radiochemical yields under low Pen-Ahx-c(RGDfK) concentration
      (50 MUM). 99mTc-[Pen-Ahx-c(RGDfK)]2 showed approximately 10-times higher integrin
      alphavbeta3 binding affinity than the monovalent compounds, Pen-Ahx-c(RGDfK) and
      c(RGDyV). In biodistribution studies, the tumor accumulation of 99mTc-[Pen-Ahx
      c(RGDfK)]2 was decreased to 77% and 43% of HPLC-purified (Pen-Ahx-c(RGDfK)-free)
      99mTc-[Pen-Ahx-c(RGDfK)]2 by the presence of 5 nmol of unlabeled Pen-Ahx-c(RGDfK)
      and Re-[Pen-Ahx-c(RGDfK)]2, respectively. 99mTc-[Pen-Ahx-c(RGDfK)]2 provided
      tumor image without removing unlabeled ligand, while a 99mTc-labeled monovalent
      probe prepared from a monovalent ligand could not. These findings indicate the
      availability of the design concept to prepare 99mTc-labeled bivalent probes with
      a variety of 99mTc core and other metallic radionuclides of clinical relevance.

PMID- 29320159
TI  - Bioinspired Nanostructured Surfaces for On-Demand Bubble Transportation.
AB  - The maneuver of small bubbles in a programmed way will advance numerous
      processes, including gas evolution reaction and aeration. Unlike in-air droplets,
      rapidly rising bubbles in liquid medium can hardly be steered through interaction
      with solid substrates, causing difficulties in maneuvering bubbles. We pattern
      and lubricate nanoporous substrates with regions of contrasting wettability that
      is similar to the back of Namib desert beetles and subsequently immerse the
      lubricated surface underwater to spontaneously form spatially patterned Nepenthes
      inspired slippery surfaces after the dewetting of lubricants. As a result,
      bubbles are confined on lubricant-infused surfaces, with their high mobility well
      preserved. The interfacial states of attached bubbles are analyzed, and their
      dynamic sliding velocities are quantified. Using the lubricated patterned
      surfaces, we further demonstrate the predefined motion of bubbles driven by
      buoyancy at a small tiling angle, as well as a self-propulsion of bubbles driven
      by surface tension force at a tilting angle of 0 degrees , respectively. The
      spatially lubricated surfaces simplify gas handling in liquid medium and have
      potential applications in fields where bubble handling is crucial.

PMID- 29320160
TI  - Efforts Aimed To Reduce Attrition in Antimalarial Drug Discovery: A Systematic
      Evaluation of the Current Antimalarial Targets Portfolio.
AB  - Malaria remains a major global health problem. In 2015 alone, more than 200
      million cases of malaria were reported, and more than 400,000 deaths occurred.
      Since 2010, emerging resistance to current front-line ACTs (artemisinin
      combination therapies) has been detected in endemic countries. Therefore, there
      is an urgency for new therapies based on novel modes of action, able to relieve
      symptoms as fast as the artemisinins and/or block malaria transmission. During
      the past few years, the antimalarial community has focused their efforts on
      phenotypic screening as a pragmatic approach to identify new hits. Optimization
      efforts on several chemical series have been successful, and clinical candidates
      have been identified. In addition, recent advances in genetics and proteomics
      have led to the target deconvolution of phenotypic clinical candidates. New
      mechanisms of action will also be critical to overcome resistance and reduce
      attrition. Therefore, a complementary strategy focused on identifying well
      validated targets to start hit identification programs is essential to reinforce
      the clinical pipeline. Leveraging published data, we have assessed the status quo
      of the current antimalarial target portfolio with a focus on the blood stage
      clinical disease. From an extensive list of reported Plasmodium targets, we have
      defined triage criteria. These criteria consider genetic, pharmacological, and
      chemical validation, as well as tractability/doability, and safety implications.
      These criteria have provided a quantitative score that has led us to prioritize
      those targets with the highest probability to deliver successful and
      differentiated new drugs.

PMID- 29320162
TI  - Electrical Characterization of Discrete Defects and Impact of Defect Density on
      Photoluminescence in Monolayer WS2.
AB  - Transition-metal dichalcogenides (TMDs) are an exciting class of 2D materials
      that exhibit many promising electronic and optoelectronic properties with
      potential for future device applications. The properties of TMDs are expected to
      be strongly influenced by a variety of defects which result from growth
      procedures and/or fabrication. Despite the importance of understanding defect
      related phenomena, there remains a need for quantitative nanometer-scale
      characterization of defects over large areas in order to understand the
      relationship between defects and observed properties, such as photoluminescence
      (PL) and electrical conductivity. In this work, we present conductive atomic
      force microscopy measurements which reveal nanometer-scale electronically active
      defects in chemical vapor deposition-grown WS2 monolayers with defect density
      varying from 2.3 * 1010 cm-2 to 4.5 * 1011 cm-2. Comparing these defect density
      measurements with PL measurements across large areas (>20 MUm distances) reveals
      a strong inverse relationship between WS2 PL intensity and defect density. We
      propose a model in which the observed electronically active defects serve as
      nonradiative recombination centers and obtain good agreement between the
      experiments and model.

PMID- 29320161
TI  - Human DNA Repair Genes Possess Potential G-Quadruplex Sequences in Their
      Promoters and 5'-Untranslated Regions.
AB  - The cellular response to oxidative stress includes transcriptional changes,
      particularly for genes involved in DNA repair. Recently, our laboratory
      demonstrated that oxidation of 2'-deoxyguanosine (G) to 8-oxo-7,8-dihydro-2'
      deoxyguanosine (OG) in G-rich potential G-quadruplex sequences (PQSs) in gene
      promoters impacts the level of gene expression up or down depending on the
      position of the PQS in the promoter. In the present report, bioinformatic
      analysis found that the 390 human DNA repair genes in the genome ontology
      initiative harbor 2936 PQSs in their promoters and 5'-untranslated regions (5'
      UTRs). The average density of PQSs in human DNA repair genes was found to be
      nearly 2-fold greater than the average density of PQSs in all coding and
      noncoding human genes (7.5 vs 4.3 per gene). The distribution of the PQSs in the
      DNA repair genes on the nontranscribed (coding) vs transcribed strands reflects
      that of PQSs in all human genes. Next, literature data were interrogated to
      select 30 PQSs to catalog their ability to adopt G-quadruplex (G4) folds in vitro
      using five different experimental tests. The G4 characterization experiments
      concluded that 26 of the 30 sequences could adopt G4 topologies in solution.
      Last, four PQSs were synthesized into the promoter of a luciferase plasmid and
      cotransfected with the G4-specific ligands pyridostatin, Phen-DC3, or BRACO-19 in
      human cells to determine whether the PQSs could adopt G4 folds. The cell studies
      identified changes in luciferase expression when the G4 ligands were present, and
      the magnitude of the expression changes dependent on the PQS and the coding vs
      template strand on which the sequence resided. Our studies demonstrate PQSs exist
      at a high density in human DNA repair gene promoters and a subset of the
      identified sequences may fold in vitro and in vivo.

PMID- 29320163
TI  - Reaction Intermediates of Nitric Oxide Synthase from Deinococcus radiodurans as
      Revealed by Pulse Radiolysis: Evidence for Intramolecular Electron Transfer from
      Biopterin to FeII-O2 Complex.
AB  - Nitric oxide synthase (NOS) is a cytochrome P450-type mono-oxygenase that
      catalyzes the oxidation of l-arginine (Arg) to nitric oxide (NO) through a
      reaction intermediate N-hydroxy-l-arginine (NHA). The mechanism underlying the
      reaction catalyzed by NOS from Deinococcus radiodurans was investigated using
      pulse radiolysis. Radiolytically generated hydrated electrons reduced the heme
      iron of NOS within 2 MUs. Subsequently, ferrous heme reacted with O2 to form a
      ferrous-dioxygen intermediate with a second-order rate constant of 2.8 * 108 M-1
      s-1. In the tetrahydrofolate (H4F)-bound enzyme, the ferrous-dioxygen
      intermediate was found to decay an another intermediate with a first-order rate
      constant of 2.2 * 103 s-1. The spectrum of the intermediate featured an
      absorption maximum at 440 nm and an absorption minimum at 390 nm. In the absence
      of H4F, this step did not proceed, suggesting that H4F was reduced with the
      ferrous-dioxygen intermediate to form a second intermediate. The intermediate
      further converted to the original ferric form with a first-order rate constant of
      4 s-1. A similar intermediate could be detected after pulse radiolysis in the
      presence of NHA, although the intermediate decayed more slowly (0.5 s-1). These
      data suggested that a common catalytically active intermediate involved in the
      substrate oxidation of both Arg and NHA may be formed during catalysis. In
      addition, we investigated the solvent isotope effects on the kinetics of the
      intermediate after pulse radiolysis. Our experiments revealed dramatic kinetic
      solvent isotope effects on the conversion of the intermediate to the ferric form,
      of 10.5 and 2.5 for Arg and NHA, respectively, whereas the faster phases were not
      affected. These data suggest that the proton transfer in DrNOS is the rate
      limiting reaction of the intermediate with the substrates.

PMID- 29320164
TI  - Mechanistic Investigations of Lysine-Tryptophan Cross-Link Formation Catalyzed by
      Streptococcal Radical S-Adenosylmethionine Enzymes.
AB  - Streptide is a ribosomally synthesized and post-translationally modified peptide
      with a unique cyclization motif consisting of an intramolecular lysine-tryptophan
      cross-link. Three radical S-adenosylmethionine enzymes, StrB, AgaB, and SuiB from
      different species of Streptococcus, have been shown to install this modification
      onto their respective precursor peptides in a leader-dependent fashion. Herein,
      we conduct detailed investigations to differentiate among several plausible
      mechanistic proposals, specifically addressing radical versus electrophilic
      addition to the indole during cross-link formation, the role of substrate side
      chains in binding in the enzyme active site, and the identity of the catalytic
      base in the reaction cycle. Our results are consistent with a radical
      electrophilic aromatic substitution mechanism for the key carbon-carbon bond
      forming step. They also elaborate on other mechanistic features that underpin
      this unique and synthetically challenging post-translational modification.

PMID- 29320165
TI  - Solution NMR Structure and Backbone Dynamics of Partially Disordered Arabidopsis
      thaliana Phloem Protein 16-1, a Putative mRNA Transporter.
AB  - Although RNA-binding proteins in plant phloem are believed to perform long
      distance systemic transport of RNA in the phloem conduit, the structure of none
      of them is known. Arabidopsis thaliana phloem protein 16-1 (AtPP16-1) is such a
      putative mRNA transporter whose structure and backbone dynamics have been studied
      at pH 4.1 and 25  degrees C by high-resolution nuclear magnetic resonance
      spectroscopy. Results obtained using basic optical spectroscopic tools show that
      the protein is unstable with little secondary structure near the physiological pH
      of the phloem sap. Fluorescence-monitored titrations reveal that AtPP16-1 binds
      not only A. thaliana RNA (Kdiss ~ 67 nM) but also sheared DNA and model dodecamer
      DNA, though the affinity for DNA is ~15-fold lower. In the solution structure of
      the protein, secondary structural elements are formed by residues 3-9 (beta1), 56
      62 (beta2), 133-135 (beta3), and 96-110 (alpha-helix). Most of the rest of the
      chain segments are disordered. The N-terminally disordered regions (residues 10
      55) form a small lobe, which conjoins the rest of the molecule via a deep and
      large irregular cleft that could have functional implications. The average order
      parameter extracted by model-free analysis of 15N relaxation and {1H}-15N
      heteronuclear NOE data is 0.66, suggesting less restricted backbone motion. The
      average conformational entropy of the backbone NH vectors is -0.31 cal mol-1 K-1.
      These results also suggest structural disorder in AtPP16-1.

PMID- 29320166
TI  - Mass Spectrometric Quantitation of Tubulin Acetylation from Pepsin-Digested Rat
      Brain Tissue Using a Novel Stable-Isotope Standard and Capture by Anti-Peptide
      Antibody (SISCAPA) Method.
AB  - Acetylation of alpha-tubulin at Lys-40 is a potential biomarker for cognitive
      deficits in various neurological disorders. However, this key post-translational
      modification (PTM) has not been previously studied with mass spectrometry, due to
      the inadequate distribution of tryptic cleavage sites. Following peptic
      digestion, a surrogate sequence containing this key PTM site was identified and
      was found to be stable and quantitatively reproducible. A highly sensitive and
      specific SISCAPA-LC-MS method for quantitating rat brain tubulin acetylation was
      developed, validated, and applied, and only required a small amount of tissue
      (2.2 mg). This workflow includes peptic digestion, stable-isotope dilution,
      capture with antiacetylated peptide antibody bound on protein G beads, and
      quantitation using LC-MS. The method allowed a lower limit of quantitation at
      2.50 pmol/mg and provided a linear range of 2.50-62.50 pmol/mg. Selectivity,
      intra and interday precision and accuracy were also validated. This method has
      been successfully applied in a preclinical study of organophosphate
      neurotoxicity, and we found that chronic exposure to chlorpyrifos led to a
      significant and persistent inhibition of brain tubulin acetylation.

PMID- 29320167
TI  - An Ultrastable Heterobimetallic Uranium(IV)/Vanadium(III) Solid Compound
      Protected by a Redox-Active Phosphite Ligand: Crystal Structure, Oxidative
      Dissolution, and First-Principles Simulation.
AB  - The first heterobimetallic uranium(IV)/vanadium(III) phosphite compound,
      Na2UV2(HPO3)6 (denoted as UVP), was synthesized via an in situ redox-active
      hydrothermal reaction. It exhibits superior hydrolytic and antioxidant stability
      compared to the majority of structures containing low-valent uranium or vanadium,
      further elucidated by first-principles simulations, and therefore shows potential
      applications in nuclear waste management.

PMID- 29320168
TI  - Linking Natural Oil Seeps from the Gulf of Mexico to Their Origin by Use of
      Fourier Transform Ion Cyclotron Resonance Mass Spectrometry.
AB  - We report chemical characterization of natural oil seeps from the Gulf of Mexico
      by Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) and
      Gas Chromatography/Atmospheric Pressure Chemical Ionization Mass Spectrometry
      (GC/APCI-MS), to highlight how FT-ICR MS can also be employed as a means to
      determine petroleum connectivity, in addition to traditional GC/MS techniques.
      The source of petroleum is the Green Canyon (GC) 600 lease block in the Gulf of
      Mexico. Within GC600, two natural oil seepage zones, Mega Plume and Birthday
      Candles, continuously release hydrocarbons and develop persistent oil slicks at
      the sea surface above them. We chemically trace the petroleum from the surface
      oil slicks to the Mega Plume seep itself, and further to a petroleum reservoir 5
      km away in lease block GC645 (Holstein Reservoir). We establish the connectivity
      between oil samples and confirm a common geological origin for the oil slicks,
      oil seep, and reservoir oil. The ratios of seven common petroleum biomarkers
      detected by GC/APCI-MS display clear similarity between the GC600 and GC645
      samples, as well as a distinct difference from another reservoir oil collected
      ~300 km away (Macondo crude oil from MC252 lease block). FT-ICR MS and principal
      component analysis (PCA) demonstrate further similarities between the GC600 and
      GC645 samples that distinctly differ from MC252. A common geographical origin is
      postulated for the GC600/GC645 samples, with petroleum migrating from the GC645
      reservoir to the oil seeps found in GC600 and up through the water column to the
      sea surface as an oil slick.

PMID- 29320169
TI  - Short-, Medium-, and Long-Chain Chlorinated Paraffins in Wildlife from Paddy
      Fields in the Yangtze River Delta.
AB  - Short-chain chlorinated paraffins (SCCPs) were added to Annex A of the Stockholm
      Convention on Persistent Organic Pollutants in April, 2017. As a consequence of
      this regulation, increasing production and usage of alternatives, such as medium-
      and long-chain chlorinated paraffins (MCCPs and LCCPs, respectively), is
      expected. Little is known about the environmental fate and behavior of MCCPs and
      LCCPs. In the present study, SCCPs, MCCPs, and LCCPs were analyzed in nine
      wildlife species from paddy fields in the Yangtze River Delta, China, using
      atmospheric pressure chemical ionization-quadrupole time-of-flight mass
      spectrometry. SCCPs, MCCPs, and LCCPs were detected in all samples at
      concentrations ranging from <91-43 000, 96-33 000, and 14-10 000 ng/g lipid,
      respectively. Most species contained primarily MCCPs (on average 44%), with the
      exception of collared scops owl and common cuckoo, in which SCCPs (43%)
      accumulated to a significantly (i.e., p < 0.05) greater extent than MCCPs (40%).
      Cl6 groups were dominant in most species except for yellow weasel and short
      tailed mamushi, which contained primarily Cl7 groups. Principal components
      analysis, together with CP concentrations and carbon stable isotope analysis
      showed that habitat and feeding habits were key factors driving CP accumulation
      and congener group patterns in wildlife. This is the first report of LCCP
      exposure in wildlife and highlights the need for data on risks associated with CP
      usage.

PMID- 29320170
TI  - Synthesis and Characterization of the Most Active Copper ATRP Catalyst Based on
      Tris[(4-dimethylaminopyridyl)methyl]amine.
AB  - The tris[(4-dimethylaminopyridyl)methyl]amine (TPMANMe2) as a ligand for copper
      catalyzed atom transfer radical polymerization (ATRP) is reported. In solution,
      the [CuI(TPMANMe2)Br] complex shows fluxionality by variable-temperature NMR,
      indicating rapid ligand exchange. In the solid state, the [CuII(TPMANMe2)Br][Br]
      complex exhibits a slightly distorted trigonal bipyramidal geometry (tau = 0.89).
      The UV-vis spectrum of [CuII(TPMANMe2)Br]+ salts is similar to those of other
      pyridine-based ATRP catalysts. Electrochemical studies of [Cu(TPMANMe2)]2+ and
      [Cu(TPMANMe2)Br]+ showed highly negative redox potentials (E1/2 = -302 and -554
      mV vs SCE, respectively), suggesting unprecedented ATRP catalytic activity.
      Cyclic voltammetry (CV) in the presence of methyl 2-bromopropionate (MBrP;
      acrylate mimic) was used to determine activation rate constant ka = 1.1 * 106 M-1
      s-1, confirming the extremely high catalyst reactivity. In the presence of the
      more active ethyl alpha-bromoisobutyrate (EBiB; methacrylate mimic), total
      catalysis was observed and an activation rate constant ka = 7.2 * 106 M-1 s-1 was
      calculated with values of KATRP ~ 1. ATRP of methyl acrylate showed a well
      controlled polymerization using as little as 10 ppm of catalyst relative to
      monomer, while side reactions such as CuI-catalyzed radical termination (CRT)
      could be suppressed due to the low concentration of L/CuI at a steady state.

PMID- 29320171
TI  - Coordination-Driven Self-Assembly of Heterotrimetallic Barrel and Bimetallic
      Cages Using a Cobalt Sandwich-Based Tetratopic Donor.
AB  - Three-dimensional molecular architectures self-assembled with tripodal and
      tetratopic donors are valuable because of their encapsulation properties. Here,
      we present Co(I)-Fe(II)-Pd(II) heterotrimetallic trifacial barrel 1, which was
      self-assembled using a newly synthesized tetratopic donor [CpCo(CbR4)] [L; Cp =
      cyclopentadienyl, Cb = cyclobudiene, and R = 4-(4-pyridylphenyl)] and a 90
      degrees  acceptor [ cis-(dppf)Pd(OTf)2] (A1; dppf = (diphenylphosphino)ferrocene
      and OTf = CF3SO3-). The heterotrimetallic barrel 1 exhibited selective 1:1
      interaction with a N, N'-dimethyl-1,4,5,8-naphthalenetetracarboxylic diimide
      guest, as revealed by 1H NMR analysis. The self-assembly of donor L with two
      other Ru(II)-based 180 degrees  acceptors [( p-cymene)2Ru2(OO?OO)(OTf)2] [OO?OO =
      6,11-dioxido-5,12-naphthacenedione (A2) and oxalate (A3)] resulted in tetragonal
      prismatic cages. Self-assembly using the longer acceptor A2 provided rare isomers
      of a tetragonal-prismatic cage by varying the orientation of the cyclopentadienyl
      moiety out-out (2a) or out-in (2b) of the cavity, whereas self-assembly using the
      shorter acceptor A3 selectively resulted in the tetragonal-prismatic cage 3. The
      three-dimensional molecular architectures 1-3 were characterized by combined
      spectroscopic and elemental analyses. The structures of molecular barrel 1 and
      prismatic cage 3 were elucidated by single-crystal X-ray analysis.

PMID- 29320172
TI  - Acetonitrile Adduct [MoReCp(MU-H)(MU-PCy2)(CO)5(NCMe)]: A Surrogate of an
      Unsaturated Heterometallic Hydride Complex.
AB  - The title compound was prepared upon irradiation of acetonitrile solutions of the
      readily available hexacarbonyl [MoReCp(MU-H)(MU-PCy2)(CO)6]. The acetonitrile
      ligand in this compound could be replaced easily by donor molecules or displaced
      upon two-electron reduction. In most cases, the substitution step was followed by
      additional processes such as insertion into the M-H bonds, E-H bond cleavage, H2
      elimination, and other transformations.

PMID- 29320173
TI  - A Spectroscopic Study on the Nitrogen Electrochemical Reduction Reaction on Gold
      and Platinum Surfaces.
AB  - The electrochemical reduction of nitrogen to ammonia on Au-based catalysts showed
      a reasonably high Coulombic efficiency. The pathway of this promising reaction,
      however, is not clear partially due to the lack of information on reaction
      intermediates. Herein, surface-enhanced infrared absorption spectroscopy (SEIRAS)
      was employed to study the reaction mechanisms of nitrogen reduction on an Au thin
      film for the first time. During the nitrogen reduction, the N2Hy species was
      detected with bands at 1453 (H-N-H bending), 1298 (-NH2 wagging), and 1109 cm-1
      (N-N stretching) at potentials below 0 V against reversible hydrogen electrode.
      This result indicates that the nitrogen reduction reaction on Au surfaces follows
      an associative mechanism, and the N=N bond in N2 tends to break simultaneously
      with the hydrogen addition. By comparison, no absorption band associated with N
      was observed on Pt surfaces under the same reaction condition. This result is
      consistent with the low efficiency of nitrogen reduction on Pt due to the much
      faster kinetics of hydrogen evolution reaction.

PMID- 29320174
TI  - Comprehensive Analysis of Changes in Crude Oil Chemical Composition during
      Biosouring and Treatments.
AB  - Biosouring in crude oil reservoirs by sulfate-reducing microbial communities
      (SRCs) results in hydrogen sulfide production, precipitation of metal sulfide
      complexes, increased industrial costs of petroleum production, and exposure
      issues for personnel. Potential treatment strategies include nitrate or
      perchlorate injections into reservoirs. Gas chromatography with vacuum
      ultraviolet ionization and high-resolution time-of-flight mass spectrometry (GC
      VUV-HTOF) and Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR
      MS) combined with electrospray ionization were applied in this study to identify
      hydrocarbon degradation patterns and product formations in crude oil samples from
      biosoured, nitrate-treated, and perchlorate-treated bioreactor column
      experiments. Crude oil hydrocarbons were selectively transformed based on
      molecular weight and compound class in the biosouring control environment. Both
      the nitrate and the perchlorate treatments significantly reduced sulfide
      production; however, the nitrate treatment enhanced crude oil biotransformation,
      while the perchlorate treatment inhibited crude oil biotransformation. Nitrogen-
      and oxygen-containing biodegradation products, particularly with chemical
      formulas consistent with monocarboxylic and dicarboxylic acids containing 10-60
      carbon atoms, were observed in the oil samples from both the souring control and
      the nitrate-treated columns but were not observed in the oil samples from the
      perchlorate-treated column. These results demonstrate that hydrocarbon
      degradation and product formation of crude oil can span hydrocarbon isomers and
      molecular weights up to C60 and double-bond equivalent classes ranging from
      straight-chain alkanes to polycyclic aromatic hydrocarbons. Our results also
      strongly suggest that perchlorate injections may provide a preferred strategy to
      treat biosouring through inhibition of biotransformation.

PMID- 29320175
TI  - Isolation of R6Si6 Dianion: A Bridged Tricyclic Isomer of Dianionic
      Hexasilabenzene.
AB  - A new strategy for the highly selective synthesis of
      tricyclo[2,2,0,02,5]hexasilanes R6Si6X2 (R = 2,4,6-Me3C6H2; X = H, Cl) and a
      bridged tricyclic R6Si6 dianion starting from the tetrachlorotrisilane
      RCl2SiSi(H)RSiCl2R (1) was described. Reduction of 1 with lithium naphthalene
      afforded tricyclohexasilane R6Si6H2 (2), which was halogenated to give the
      dichloride R6Si6Cl2 (3). Reduction of 3 with four equivalents of potassium
      graphite in the presence of 18-crown-6 afforded the first R6Si6 dianion (5)
      paired with [K(18-crown-6)]+2 counterions. The dianion 5 could act as a two
      electron reductant toward transition metal halides and a nucleophile toward
      chlorosilanes. These reactions allowed the efficient and selective access to
      three types of silicon cages. The structures of the representative cages were
      confirmed by X-ray diffraction studies. Density functional theory calculations on
      5 indicate that the negative charges are localized mainly on the anionic silicon
      atoms.

PMID- 29320177
TI  - Holomorphic Hartree-Fock Theory: The Nature of Two-Electron Problems.
AB  - We explore the existence and behavior of holomorphic restricted Hartree-Fock (h
      RHF) solutions for two-electron problems. Through algebraic geometry, the exact
      number of solutions with n basis functions is rigorously identified as 1/2(3n -
      1), proving that states must exist for all molecular geometries. A detailed study
      on the h-RHF states of HZ (STO-3G) then demonstrates both the conservation of
      holomorphic solutions as geometry or atomic charges are varied and the emergence
      of complex h-RHF solutions at coalescence points. Using catastrophe theory, the
      nature of these coalescence points is described, highlighting the influence of
      molecular symmetry. The h-RHF states of HHeH2+ and HHeH (STO-3G) are then
      compared, illustrating the isomorphism between systems with two electrons and two
      electron holes. Finally, we explore the h-RHF states of ethene (STO-3G) by
      considering the pi electrons as a two-electron problem and employ NOCI to
      identify a crossing of the lowest energy singlet and triplet states at the
      perpendicular geometry.

PMID- 29320176
TI  - Discovery of Bisubstrate Inhibitors of Nicotinamide N-Methyltransferase (NNMT).
AB  - Nicotinamide N-methyltransferase (NNMT) catalyzes the N-methylation of pyridine
      containing compounds using the cofactor S-5'-adenosyl-l-methionine (SAM) as the
      methyl group donor. Through the regulation of the levels of its substrates,
      cofactor, and products, NNMT plays an important role in physiology and
      pathophysiology. Overexpression of NNMT has been implicated in various human
      diseases. Potent and selective small-molecule NNMT inhibitors are valuable
      chemical tools for testing biological and therapeutic hypotheses. However, very
      few NNMT inhibitors have been reported. Here, we describe the discovery of a
      bisubstrate NNMT inhibitor MS2734 (6) and characterization of this inhibitor in
      biochemical, biophysical, kinetic, and structural studies. Importantly, we
      obtained the first crystal structure of human NNMT in complex with a small
      molecule inhibitor. The structure of the NNMT-6 complex has unambiguously
      demonstrated that 6 occupied both substrate and cofactor binding sites. The
      findings paved the way for developing more potent and selective NNMT inhibitors
      in the future.

PMID- 29320178
TI  - Novel K-Ras G12C Switch-II Covalent Binders Destabilize Ras and Accelerate
      Nucleotide Exchange.
AB  - The success of targeted covalent inhibitors in the global pharmaceutical industry
      has led to a resurgence of covalent drug discovery. However, covalent inhibitor
      design for flexible binding sites remains a difficult task due to a lack of
      methodological development. Here, we compared covalent docking to empirical
      electrophile screening against the highly dynamic target K-RasG12C. While the
      overall hit rate of both methods was comparable, we were able to rapidly progress
      a docking hit to a potent irreversible covalent binder that modifies the
      inactive, GDP-bound state of K-RasG12C. Hydrogen-deuterium exchange mass
      spectrometry was used to probe the protein dynamics of compound binding to the
      switch-II pocket and subsequent destabilization of the nucleotide-binding region.
      SOS-mediated nucleotide exchange assays showed that, contrary to prior switch-II
      pocket inhibitors, these new compounds appear to accelerate nucleotide exchange.
      This study highlights the efficiency of covalent docking as a tool for the
      discovery of chemically novel hits against challenging targets.

PMID- 29320179
TI  - Trifluoromethyl Vinyl Sulfide: A Building Block for the Synthesis of CF3S
      Containing Isoxazolidines.
AB  - Trifluoromethyl vinyl sulfide, a potential building block for pharmaceutically
      and agrochemically relevant products, is prepared and used for the first time in
      high-pressure-mediated 1,3-dipolar cycloaddition reactions with nitrones to
      synthesize (trifluoromethyl)sulfanyl isoxazolidines.

PMID- 29320180
TI  - Inner and Outer Recursive Neural Networks for Chemoinformatics Applications.
AB  - Deep learning methods applied to problems in chemoinformatics often require the
      use of recursive neural networks to handle data with graphical structure and
      variable size. We present a useful classification of recursive neural network
      approaches into two classes, the inner and outer approach. The inner approach
      uses recursion inside the underlying graph, to essentially "crawl" the edges of
      the graph, while the outer approach uses recursion outside the underlying graph,
      to aggregate information over progressively longer distances in an orthogonal
      direction. We illustrate the inner and outer approaches on several examples. More
      importantly, we provide open-source implementations [available at
      www.github.com/Chemoinformatics/InnerOuterRNN and cdb.ics.uci.edu ] for both
      approaches in Tensorflow which can be used in combination with training data to
      produce efficient models for predicting the physical, chemical, and biological
      properties of small molecules.

PMID- 29320181
TI  - Stereospecific Stille Cross-Couplings Using Mn(II)Cl2.
AB  - Cross-coupling reactions are a staple in organic synthesis, especially for C-C
      bond formation with sp- and sp2-carbon electrophiles. In recent years, the range
      of accessible C-C bonds has been extended to stereogenic centers which expedites
      access to greater molecular complexity. However, these reactions predominantly
      depend upon late transition metal (LTM) catalysts whose cost, toxicity, and/or
      environmental impact have come under increasing scrutiny and governmental
      regulation. Here, we report Mn(II)Cl2 complexes alone, or with assistance from
      copper, catalyze the stereospecific cross-coupling of alpha-alkoxyalkylstannanes
      with organic electrophiles with complete retention of configuration.

PMID- 29320182
TI  - Reconstruction of HMBC Correlation Networks: A Novel NMR-Based Contribution to
      Metabolite Mixture Analysis.
AB  - A new in silico method is introduced for the dereplication of natural metabolite
      mixtures based on HMBC and HSQC spectra that inform about short-range and long
      range H-C correlations occurring in the carbon skeleton of individual chemical
      entities. Starting from the HMBC spectrum of a metabolite mixture, an algorithm
      was developed in order to recover individualized HMBC footprints of the mixture
      constituents. The collected H-C correlations are represented by a network of NMR
      peaks connected to each other when sharing either a 1H or 13C chemical shift
      value. The network obtained is then divided into clusters using a community
      detection algorithm, and finally each cluster is tentatively assigned to a
      molecular structure by means of a NMR chemical shift database containing the
      theoretical HMBC and HSQC correlation data of a range of natural metabolites. The
      proof of principle of this method is demonstrated on a model mixture of 3 known
      natural compounds and then on a real-life bark extract obtained from the common
      spruce (Picea abies L.).

PMID- 29320183
TI  - Six Trikentrin-like Cyclopentanoindoles from Trikentrion flabelliforme. Absolute
      Structural Assignment by NMR and ECD.
AB  - Six new cyclopenta[g]indoles were isolated from a West Australian sponge,
      Trikentrion flabelliforme Hentschel, 1912, and their structures elucidated by
      integrated spectroscopic analysis. The compounds are analogues of previously
      described trikentrins, herbindoles, and trikentramides from related Axinellid
      sponges. The assignment of absolute configuration of the new compounds was
      carried out largely by comparative analysis of specific rotation, calculated and
      measured ECD, and exploiting van't Hoff's principle of optical superposition.
      Five of the new compounds were chemically interconverted to establish their
      stereochemical relationships, leading to a simple chiroptical mnemonic for
      assignment of the this family of chiral indoles. The first biosynthetic
      hypothesis is advanced to explain the origin of the trikentrin-herbinole family
      and proposes a pyrrole-carboxylic thioester-initiated polyketide synthase
      mechanism.

PMID- 29320184
TI  - Unusual Rearrangement of an N-Donor-Functionalized N-Heterocyclic Carbene Ligand
      on Group 8 Metals.
AB  - We report an unexpected rearrangement of a deprotonated picolyl-functionalized N
      heterocyclic carbene (NHC) ligand from N,C-chelate to N,N-chelate in three-legged
      piano-stool Fe(II) and Ru(II) complexes. The reaction mechanism has been explored
      for one of the Fe(II) complexes. Experimental and computational studies suggest
      an unusual intermediate featuring a four-membered chelate ring, where the NHC and
      the alpha-carbon of one of the N-substituents coordinate to the Fe(II) center. A
      possible Fe-alkylidene intermediate has also been predicted by computations.

PMID- 29320185
TI  - Force Field Benchmark of the TraPPE_UA for Polar Liquids: Density, Heat of
      Vaporization, Dielectric Constant, Surface Tension, Volumetric Expansion
      Coefficient, and Isothermal Compressibility.
AB  - The transferable potential for a phase equilibria force field in its united-atom
      version, TraPPE_UA, is evaluated for 41 polar liquids that include alcohols,
      thiols, ethers, sulfides, aldehydes, ketones, and esters to determine its ability
      to reproduce experimental properties that were not included in the
      parametrization procedure. The intermolecular force field parameters for pure
      components were fit to reproduce experimental boiling temperature, vapor-liquid
      coexisting densities, and critical point (temperature, density, and pressure)
      using Monte Carlo simulations in different ensembles. The properties calculated
      in this work are liquid density, heat of vaporization, dielectric constant,
      surface tension, volumetric expansion coefficient, and isothermal
      compressibility. Molecular dynamics simulations were performed in the gas and
      liquid phases, and also at the liquid-vapor interface. We found that relative
      error between calculated and experimental data is 1.2% for density, 6% for heat
      of vaporization, and 6.2% for surface tension, in good agreement with the
      experimental data. The dielectric constant is systematically underestimated, and
      the relative error is 37%. Evaluating the performance of the force field to
      reproduce the volumetric expansion coefficient and isothermal compressibility
      requires more experimental data.

PMID- 29320186
TI  - Lewis Acid Assisted Electrophilic Fluorine-Catalyzed Pinacol Rearrangement of
      Hydrobenzoin Substrates: One-Pot Synthesis of (+/-)-Latifine and (+/-)
      Cherylline.
AB  - A microwave-irradiated solvent-free pinacol rearrangement of hydrobenzoin
      substrates catalyzed by a combination of N-fluorobenzenesulfonimide and
      FeCl3.6H2O was developed. Its selectivity was first investigated by density
      functional theory (DFT) calculations. Then the functional group tolerance was
      examined by synthesizing a series of substrates designed based on the insight
      provided by the DFT calculations. The application of the methodology was
      demonstrated by the efficient one-pot synthesis of (+/-)-latifine and (+/-)
      cherylline, both are 4-aryltetrahydroisoquinoline alkaloids isolated from
      Amaryllidacecae plants.

PMID- 29320187
TI  - DFT Modeling of Cross-Linked Polyethylene: Role of Gold Atoms and Dispersion
      Interactions.
AB  - Using DFT modeling, we analyze the concerted action of gold atoms and dispersion
      interactions in cross-linked polyethylene. Our model consists of two oligomer
      chains (PEn) with 7, 11, 15, 19, or 23 carbon atoms in each oligomer cross-linked
      with one to three Au atoms through C-Au-C bonds. In structures with a single gold
      atom the C-Au-C bond is located in the central position of the oligomer. Binding
      energies (BEs) with respect to two oligomer radical fragments and Au are as high
      as 362-489 kJ/mol depending on the length of the oligomer chain. When the
      dispersion contribution in PEn-Au-PEn oligomers is omitted, BE is almost
      independent of the number of carbon atoms, lying between 293 and 296 kJ/mol. The
      dispersion energy contributions to BEs in PEn-Au-PEn rise nearly linearly with
      the number of carbon atoms in the PEn chain. The carbon-carbon distance in the C
      Au-C moiety is around 4.1 A, similar to the bond distance between saturated
      closed shell chains in the polyethylene crystal. BEs of pure saturated closed
      shell PEn-PEn oligomers are 51-187 kJ/mol. Both Au atoms and dispersion
      interactions contribute considerably to the creation of nearly parallel chains of
      oligomers with reasonably high binding energies.

PMID- 29320188
TI  - Hydrogen-Bonding Acceptor Character of Be3, the Beryllium Three-Membered Ring.
AB  - The ability of Be3 as a hydrogen bond acceptor has been explored by studying the
      potential complexes between this molecule and a set of hydrogen bond donors (HF,
      HCl, HNC, HCN, H2O, and HCCH). The electronic structure calculations for these
      complexes were carried out at the MP2 and CCSD(T) computational levels together
      with an extensive NBO, ELF, AIM, and electrostatic potential characterization of
      the isolated Be3 system. In all the complexes, the Be-Be sigma bond acts as
      electron donor, with binding energies between 19 and 6 kJ mol-1. A comparison
      with the analogous cyclopropane:HX complexes shows similar binding energies and
      contributions of the DFT-SAPT energetic terms. A blue-shift of the harmonic
      frequencies of Be3 is observed upon complexation.

PMID- 29320189
TI  - Free-Energy Analysis of Peptide Binding in Lipid Membrane Using All-Atom
      Molecular Dynamics Simulation Combined with Theory of Solutions.
AB  - All-atom molecular dynamics (MD) simulations are performed to examine the
      stabilities of a variety of binding configurations of alamethicin, a 20-amino
      acid amphipathic peptide, in the bilayers of 1-palmitoyl-2-oleoyl
      phosphatidylcholine (POPC) and 1,2-dimyristoyl- sn-glycero-3-phosphatidylcholine
      (DMPC). The binding free energy of alamethicin is calculated through a
      combination of MD simulation and the energy-representation theory of solutions,
      and it is seen that the transmembrane configuration is stable in both membranes.
      A surface-bound state is also found to be stable due to the balance between the
      attractive and repulsive interactions of the peptide with lipid and water, and
      the key role of water is pointed out for the stability in the interfacial region.
      A difference between the POPC and DMPC systems is noted when the polar C-terminal
      domain is buried in the hydrophobic region of the membrane. In POPC, the peptide
      is unfavorably located with that configuration due to the loss of electrostatic
      interaction between the peptide and lipid.

PMID- 29320190
TI  - Electronic and Nonlinear Optical Properties of l-Histidine on Silver: A
      Theoretical and Experimental Approach.
AB  - An investigation of the electrostatic interactions between histidine and silver
      have been analyzed using density functional theory (DFT). Variations in the
      structural parameters were identified to be significant at those atoms of
      histidine near the silver cluster. The shifting of frontier molecular orbitals,
      reduction in bandgap, molecular electrostatic potential (MEP), and overlap of
      natural bond orbitals (NBO) between silver and histidine have been theoretically
      calculated. The results confirm the redistribution of charges consequent to the
      process of adsorption. On the basis of time-dependent density functional theory
      (TDDFT), two peaks were generated at 301 and 409 nm in the simulated UV-vis
      spectrum. Theoretical vibrational Raman analysis of the investigated molecules
      strongly confirms the process of adsorption. Nonlinear optical (NLO) properties
      are predicted by theoretical studies and confirmed experimentally via open
      aperture Z-scan. The adsorption of histidine on silver enhances the NLO
      parameters, indicating that it is a promising candidate for NLO devices.

PMID- 29320191
TI  - Synthesis of 2-Aminoimidazolones and Imidazolones by (3 + 2) Annulation of
      Azaoxyallyl Cations.
AB  - The first examples of (3 + 2) annulations between azaoxyallyl cations and
      cyanamides and nitriles to give the corresponding 2-aminoimidazolones and
      imidazolones are reported. On the basis of the isolation of unexpected imidate
      products with certain substrates, it is proposed that the reaction proceeds via
      fast kinetic O-alkylation followed by rearrangement to the thermodynamically
      favored 2-aminoimidazolones and imidazolones. The method was applied to the
      formal synthesis of the antihypertensive drug irbesartan.

PMID- 29320192
TI  - Photoinduced Birefringent Pattern and Photoinactivation of Liquid-Crystalline
      Copolymer Films with Benzoic Acid and Phenylaldehyde Side Groups.
AB  - In situ formation of N-benzylideneaniline (NBA) side groups achieved photoinduced
      cooperative reorientation of photoinactive copolymers with phenylaldehyde (PA)
      and benzoic acid (BA) side groups doped with 4-methoxyaniline (AN) molecules.
      Thermally stimulated molecular reorientation of the side groups was generated due
      to the axis-selective photoreaction of the NBA moieties. Selective coating with
      AN on the copolymer film formed NBA moieties in the desired region, resulting in
      a photoinduced birefringent pattern. Additionally, postannealing at an elevated
      temperature for a long time attained photoinactivation of the reoriented film,
      and recoating with AN to form NBA achieved the multiple birefringent patterns and
      repatterning of the reoriented structures. The slow thermal hydrolysis of NBA,
      which was 50 times slower than the thermally stimulated self-organization of the
      side groups due to the presence of BA side groups, contributed to the
      photodurability of the reoriented film and multiple birefringent patterns.

PMID- 29320193
TI  - Anionic Triflyldiazomethane: Generation and Its Application for Synthesis of
      Pyrazole-3-triflones via [3 + 2] Cycloaddition Reaction.
AB  - The synthesis of pyrazole triflones containing a triflyl group at the 3-position
      is disclosed. Treatment of 2-diazo-1-phenyl-2-((trifluoromethyl)sulfonyl)ethan-1
      one with nitroalkenes under basic conditions gave pharmaceutically attractive
      pyrazole 3-triflones in good to high yields. The generation of anionic
      triflyldiazomethane species followed by the [3 + 2] cycloaddition reaction with
      nitroalkenes is proposed for this transformation. 3
      (Difluoromethanesulfonyl)pyrazoles were also synthesized by using a previously
      unknown anionic (difluoromethanesulfonyl)diazomethane species under a similar
      strategy.

PMID- 29320194
TI  - Determining Li+-Coupled Redox Targeting Reaction Kinetics of Battery Materials
      with Scanning Electrochemical Microscopy.
AB  - The redox targeting reaction of Li+-storage materials with redox mediators is the
      key process in redox flow lithium batteries, a promising technology for next
      generation large-scale energy storage. The kinetics of the Li+-coupled
      heterogeneous charge transfer between the energy storage material and redox
      mediator dictates the performance of the device, while as a new type of charge
      transfer process it has been rarely studied. Here, scanning electrochemical
      microscopy (SECM) was employed for the first time to determine the interfacial
      charge transfer kinetics of LiFePO4/FePO4 upon delithiation and lithiation by a
      pair of redox shuttle molecules FcBr2+ and Fc. The effective rate constant keff
      was determined to be around 3.70-6.57 * 10-3 cm/s for the two-way pseudo-first
      order reactions, which feature a linear dependence on the composition of LiFePO4,
      validating the kinetic process of interfacial charge transfer rather than bulk
      solid diffusion. In addition, in conjunction with chronoamperometry measurement,
      the SECM study disproves the conventional "shrinking-core" model for the
      delithiation of LiFePO4 and presents an intriguing way of probing the phase
      boundary propagations induced by interfacial redox reactions. This study
      demonstrates a reliable method for the kinetics of redox targeting reactions, and
      the results provide useful guidance for the optimization of redox targeting
      systems for large-scale energy storage.

PMID- 29320195
TI  - Microstructure of Pharmaceutical Semicrystalline Dispersions: The Significance of
      Polymer Conformation.
AB  - The microstructure of pharmaceutical semicrystalline solid dispersions has
      attracted extensive attention due to its complexity that might result in the
      diversity in physical stability, dissolution behavior, and pharmaceutical
      performance of the systems. Numerous factors have been reported that dictate the
      microstructure of semicrystalline dispersions. Nevertheless, the importance of
      the complicated conformation of the polymer has never been elucidated. In this
      study, we investigate the microstructure of dispersions of polyethylene glycol
      and active pharmaceutical ingredients by small-angle X-ray scattering and high
      performance differential scanning calorimetry. Polyethylene glycol with molecular
      weight of 2000 g/mol (PEG2000) and 6000 g/mol (PEG6000) exhibited remarkable
      discrepancy in the lamellar periodicity in dispersions with APIs which was
      attributed to the differences in their folding behavior. The long period of
      PEG2000 always decreased upon aging-induced exclusion of APIs from the
      interlamellar region of extended chain crystals whereas the periodicity of
      PEG6000 may decrease or increase during storage as a consequence of the
      competition between the drug segregation and the lamellar thickening from
      nonintegral-folded into integral-folded chain crystals. These processes were in
      turn significantly influenced by the crystallization tendency of the
      pharmaceutical compounds, drug-polymer interactions, as well as the dispersion
      composition and crystallization temperature. This study highlights the
      significance of the polymer conformation on the microstructure of semicrystalline
      systems that is critical for the preparation of solid dispersions with consistent
      and reproducible quality.

PMID- 29320196
TI  - Correction to Regioselective Synthesis, NMR, and Crystallographic Analysis of N1
      Substituted Pyrazoles.

PMID- 29320197
TI  - Synthesis of Thelepamide via Catalyst-Controlled 1,4-Addition of Cysteine
      Derivatives and Structure Revision of Thelepamide.
AB  - The first enantioselective total synthesis and structural reassignment of (-)
      thelepamide, a cytotoxic tetraketide-amino acid from the marine worm Thelepus
      crispus, is reported. A convergent approach provides access to all thelepamide
      diastereomers in six steps from four simple building blocks. Key features of the
      synthesis include the application of Melchiorre's organocatalytic thia-Michael
      reaction and a sonication-assisted assembly of an unprecedented N,O-acetal
      hemiacetal moiety. The corrected structure was confirmed by NMR-DFT analysis.

PMID- 29320198
TI  - Improvement of Anion Transport Systems by Modulation of Chalcogen Interactions:
      The influence of solvent.
AB  - A series of potential anion transporters, dithieno[3,2-b;2',3'-d]thiophenes
      (DTT), involving anion-chalcogen interactions have been studied by analyzing the
      interaction energy, geometry, and charge transfer. It was found that gas phase
      calculations show very negative interaction energies with short anion-chalcogen
      distances, but when solvent effects are considered, the interaction energy values
      decreased drastically concomitantly with an elongation on the interatomic
      distances. To enhance the chalcogen interaction between the DTT derivatives and
      the anion, increasing the anion transporter capacity, bisisothioazole moiety was
      considered; i.e., the sigma-hole of the chalcogen atom was modulated by
      substitution of the adjacent carbon by a nitrogen atom in the S-C axis,
      increasing the depth of the sigma-hole and therefore the interaction between the
      chalcogen and anion. Finally, different anions were analyzed within the
      complexes, finding that F- and NO3- would be the best candidates to form
      complexes and possibly displace other anions such as Cl- or Br-.

PMID- 29320199
TI  - Theoretical Insights Into the Excited State Double Proton Transfer Mechanism of
      Deep Red Pigment Alkannin.
AB  - As the most important component of deep red pigments, alkannin is investigated
      theoretically in detail based on time-dependent density functional theory (TDDFT)
      method. Exploring the dual intramolecular hydrogen bonds (O1-H2...O3 and O4
      H5...O6) of alkannin, we confirm the O1-H2...O3 may play a more important role in
      the first excited state than the O4-H5...O6 one. Infrared (IR) vibrational
      analyses and subsequent charge redistribution also support this viewpoint. Via
      constructing the S1-state potential energy surface (PES) and searching transition
      state (TS) structures, we illuminate the excited state double proton transfer
      (ESDPT) mechanism of alkannin is the stepwise process that can be first launched
      by the O1-H2...O3 hydrogen bond wire in gas state, acetonitrile (CH3CN) and
      cyclohexane (CYH) solvents. We present a novel mechanism that polar aprotic
      solvents can contribute to the first-step proton transfer (PT) process in the S1
      state, and nonpolar solvents play important roles in lowering the potential
      energy barrier of the second-step PT reaction.

PMID- 29320200
TI  - Electrostatic Estimation of Intercalant Jump-Diffusion Barriers Using Finite-Size
      Ion Models.
AB  - We report on a scheme for estimating intercalant jump-diffusion barriers that are
      typically obtained from demanding density functional theory-nudged elastic band
      calculations. The key idea is to relax a chain of states in the field of the
      electrostatic potential that is averaged over a spherical volume using different
      finite-size ion models. For magnesium migrating in typical intercalation
      materials such as transition-metal oxides, we find that the optimal model is a
      relatively large shell. This data-driven result parallels typical assumptions
      made in models based on Onsager's reaction field theory to quantitatively
      estimate electrostatic solvent effects. Because of its efficiency, our potential
      of electrostatics-finite ion size (PfEFIS) barrier estimation scheme will enable
      rapid identification of materials with good ionic mobility.

PMID- 29320201
TI  - Synergistic Photo-Copper-Catalyzed Hydroxylation of (Hetero)aryl Halides with
      Molecular Oxygen.
AB  - Photoredox-mediated copper-catalyzed hydroxylation of (hetero)aryl halides
      (including chlorides, bromides, and iodides) with O2 at room temperature has been
      developed. Preliminary mechanistic studies indicate no arylcopper intermediate
      and that aryl radicals are involved in this procedure. 18O-labeling experiments
      confirm the hydroxyl oxygen atom originated from molecular oxygen.

PMID- 29320202
TI  - Nanoscale Heterogeneities Drive Enhanced Binding and Anomalous Diffusion of
      Nanoparticles in Model Biomembranes.
AB  - Interaction of functional nanoparticles with cells and model biomembranes has
      been widely studied to evaluate the effectiveness of the particles as potential
      drug delivery vehicles and bioimaging labels as well as in understanding
      nanoparticle cytotoxicity effects. Charged nanoparticles, in particular, with
      tunable surface charge have been found to be effective in targeting cellular
      membranes as well as the subcellular matrix. However, a microscopic understanding
      of the underlying physical principles that govern nanoparticle binding, uptake,
      or diffusion on cells is lacking. Here, we report the first experimental studies
      of nanoparticle diffusion on model biomembranes and correlate this to the
      existence of nanoscale dynamics and structural heterogeneities using super
      resolution stimulated emission depletion (STED) microscopy. Using confocal and
      STED microscopy coupled with fluorescence correlation spectroscopy (FCS), we
      provide novel insight on why these nanoparticles show enhanced binding on two
      component lipid bilayers as compared to single-component membranes and how
      binding and diffusion is correlated to subdiffraction nanoscale dynamics and
      structure. The enhanced binding is also dictated, in part, by the presence of
      structural and dynamic heterogeneity, as revealed by STED-FCS studies, which
      could potentially be used to understand enhanced nanoparticle binding in raft
      like domains in cell membranes. In addition, we also observe a clear correlation
      between the enhanced nanoparticle diffusion on membranes and the extent of
      membrane penetration by the nanoparticles. Our results not only have a
      significant impact on our understanding of nanoparticle binding and uptake as
      well as diffusion in cell and biomembranes, but have very strong implications for
      uptake mechanisms and diffusion of other biomolecules, like proteins on cell
      membranes and their connections to functional membrane nanoscale platform.

PMID- 29320203
TI  - Electronically Tunable Perfect Absorption in Graphene.
AB  - The demand for dynamically tunable light modulation in flat optics applications
      has grown in recent years. Graphene nanostructures have been extensively studied
      as means of creating large effective index tunability, motivated by theoretical
      predictions of the potential for unity absorption in resonantly excited graphene
      nanostructures. However, the poor radiative coupling to graphene plasmonic
      nanoresonators and low graphene carrier mobilities from imperfections in
      processed graphene samples have led to low modulation depths in experimental
      attempts at creating tunable absorption in graphene devices. Here we demonstrate
      electronically tunable perfect absorption in graphene, covering less than 10% of
      the surface area, by incorporating multiscale nanophotonic structures composed of
      a low-permittivity substrate and subwavelength noble metal plasmonic antennas to
      enhance the radiative coupling to deep subwavelength graphene nanoresonators. To
      design the structures, we devised a graphical method based on effective surface
      admittance, elucidating the origin of perfect absorption arising from critical
      coupling between radiation and graphene plasmonic modes. Experimental
      measurements reveal 96.9% absorption in the graphene plasmonic nanostructure at
      1389 cm-1, with an on/off modulation efficiency of 95.9% in reflection.

PMID- 29320204
TI  - Dehydration of Amides to Nitriles under Conditions of a Catalytic Appel Reaction.
AB  - A highly expedient protocol for a catalytic Appel-type dehydration of amides to
      nitriles has been developed that employs oxalyl chloride and triethylamine along
      with triphenylphosphine oxide as a catalyst. The reactions are usually complete
      in less than 10 min with only a 1 mol % catalyst loading. The reaction scope
      includes aromatic, heteroaromatic, and aliphatic amides, including derivatives of
      alpha-hydroxy and alpha-amino acids.

PMID- 29320205
TI  - Heavy Atom Secondary Kinetic Isotope Effect on H-Tunneling.
AB  - Although frequently employed, heavy atom kinetic isotope effects (KIE) have not
      been reported for quantum mechanical tunneling reactions. Here we examine the
      secondary KIE through 13C-substitution of the carbene atom in
      methylhydroxycarbene (H3C-C-OH) in its [1,2]H-tunneling shift reaction to
      acetaldehyde (H3C-CHO). Our study employs matrix-isolation IR spectroscopy in
      various inert gases and quantum chemical computations. Depending on the choice of
      the matrix host gas, the KIE varies within a range of 1.0 in xenon to 1.4 in
      neon. A KIE of 1.1 was computed using the Wentzel-Kramers-Brillouin (WKB)
      CVT/SCT, and instanton approaches for the gas phase at the B3LYP/cc-pVTZ level of
      theory. Computations with explicit consideration of the noble gas environment
      indicate that the surrounding atoms influence the tunneling reaction barrier
      height and width. The tunneling half-lives computed with the WKB approach are in
      good agreement with the experimental results in the different noble gases.

PMID- 29320206
TI  - Domino Carbopalladation/C-H Activation as a Quick Access to Polycyclic
      Frameworks.
AB  - A new type of domino reaction for synthesis of heterocycles fusing the important
      bioactive cores, such as oxindole, indoline, and isoquinoline, is presented. Upon
      exposure to the very common palladium catalyst, the conceptually designed N
      alkenyl iodobiaryls undergo a sequential carbopalladation/C-H activation to build
      polycyclic frameworks. These novel unique frameworks may provide structure
      sources in fragment-based drug discovery.

PMID- 29320207
TI  - Nickel(0)-Catalyzed Inert C-O Bond Functionalization: Organo Rare-Earth Metal
      Complex as the Coupling Partner.
AB  - An organo rare-earth metal complex has been employed as a highly efficient
      nucleophile in Ni(0)-catalyzed C-O bond functionalization. The optimized
      catalytic system which consists of Ni(cod)2, PCy3, and t-BuONa could smoothly
      convert 1 equiv of naphthyl ethers to alkylated naphthalene analogues with 0.4
      equiv of Ln(CH2SiMe3)3(THF)2, delivering good to excellent yields. The reaction
      system could also activate the ArCH2-O bond with mild base.

PMID- 29320208
TI  - Ultracompact Pseudowedge Plasmonic Lasers and Laser Arrays.
AB  - Concentrating light at the deep subwavelength scale by utilizing plasmonic
      effects has been reported in various optoelectronic devices with intriguing
      phenomena and functionality. Plasmonic waveguides with a planar structure exhibit
      a two-dimensional degree of freedom for the surface plasmon; the degree of
      freedom can be further reduced by utilizing metallic nanostructures or
      nanoparticles for surface plasmon resonance. Reduction leads to different
      lightwave confinement capabilities, which can be utilized to construct plasmonic
      nanolaser cavities. However, most theoretical and experimental research efforts
      have focused on planar surface plasmon polariton (SPP) nanolasers. In this study,
      we combined nanometallic structures intersecting with ZnO nanowires and realized
      the first laser emission based on pseudowedge SPP waveguides. Relative to current
      plasmonic nanolasers, the pseudowedge plasmonic lasers reported in our study
      exhibit extremely small mode volumes, high group indices, high spontaneous
      emission factors, and high Purell factors beneficial for the strong interaction
      between light and matter. Furthermore, we demonstrated that compact plasmonic
      laser arrays can be constructed, which could benefit integrated plasmonic
      circuits.

PMID- 29320209
TI  - [Pulmonary contusion].
AB  - Pulmonary contusion is a common finding after blunt chest trauma. It occurs in 23
      35% of all cases. Alveolar capillaries are injured due to the trauma, which
      results in accumulation of blood and other fluids within lung tissue. The fluids
      interfere with gas exchange, leading to hypoxemia. The consequences of pulmonary
      contusion include ventilation/perfusion mismatching, increased AV shunts and loss
      of compliance of lung parenchyma. These physiological consequences are manifested
      within hours from injury and usually resolve in 7 days. Computed tomography (CT)
      is a sensitive and main diagnostic tool. Clinical symptoms include hypoxemia and
      hypercapnia, manifested predominantly during 72 hours from injury. Patients are
      treated primarily conservatively; surgery may be needed due to haemothorax
      associated with lung contusion or progression of AV shunts due to localized
      pulmonary contusion.Key words: pulmonary contusion blunt chest trauma computed
      tomography.

PMID- 29320210
TI  - [Ruptures of the diaphragm].
AB  - INTRODUCTION: The diaphragm is a flat muscle that divides the thoracic and
      abdominal cavities, and it is one of the most important muscles involved in
      respiration. Traumas of the diaphragm include its rupture caused by an external
      force, resulting in blunt or penetrating injuries. Diaphragmatic rupture is
      associated with the risk of a prolapse (i.e. not a typical hernia) of abdominal
      organs into the pleural cavity. The rupture may occur due to a blunt injury of
      the chest or abdomen, or due to penetrating injuries (gunshots, stab wounds,
      foreign bodies) in the lower part of the chest and epigastrium. Ruptures never
      heal spontaneously and always require suture of the diaphragmatic defect. Most
      acute rupture cases are managed using laparotomy; thoracotomy is preferred for
      lately recognised ruptures to facilitate the removal of adhesions in the thoracic
      cavity developed between the diaphragmatic defect and a lung. Thirty one patients
      with diaphragmatic rupture were operated at the 3rd Department of Surgery of the
      1st Faculty of Medicine, Charles University and University Hospital Motol between
      2006 and 2016. Acute rupture was present in 60% of the cases and chronic in 40%.
      Right-sided rupture was found in 20% and left-sided in 80%. CONCLUSION: The
      authors describe surgical treatment of diaphragmatic ruptures. They recommend an
      early surgical treatment if diaphragmatic rupture is recognized. Generally, the
      prognosis of the patients depends on availability of professional health care;
      ideally, these patients should be treated at specialised traumacentres with
      specialists for abdominal and thoracic surgery. The authors advise against
      establishing injudicious thoracic drainage in cases where diaphragmatic rupture
      with herniation of abdominal organs into the thorax may be present.Key words:
      polytrauma - acute rupture of diaphragm - chronic rupture - suture - patch.

PMID- 29320211
TI  - [Chest injuries in polytraumatized children].
AB  - Chest injuries in children are part of polytrauma resulting from high-energy
      violence, most often caused by traffic accidents. Blunt chest injuries (95%) are
      significantly more frequent than penetrating injuries (5%). Lung contusion, rib
      fracture, pneumothorax or haemothorax, are the more common injuries, but
      tracheobronchial rupture, cardiac or diaphragmatic injuries may also occur. The
      anterior X-ray image remains the basic examination method for isolated chest
      injuries. CT trauma scan with a contrast medium is done in polytraumatized
      children. Blunt injuries of intra-thoracic organs in haemodynamically stable
      children are treated mostly conservatively (85%) under full monitoring at the
      ICU. Surgical treatment is necessary in a minority of patients. Mortality and
      morbidity of patients with chest injury depend on the actual combination of
      multiple body systems injury. The severity of total injury can be predicted using
      objective scoring systems (Abbreviated Injury Scale=AIS; Injury Severity
      Score=ISS). Overall mortality ranges from 6 to 20%. Mortality is high but this is
      mainly due to associated head injuries.Key words: multiple trauma thoracic trauma
      - paediatric lung contusion Injury Severity Score=ISS.

PMID- 29320212
TI  - [Assessment of thoracic trauma at the 1st Department of Surgery in Brno (1
      January 2011 - 31 December 2015)].
AB  - INTRODUCTION: The number of cases of thorax injury increased steadily between
      2011 and 2015. This is probably related to a more active lifestyle of the younger
      generations and also to the increasing average age of citizens. The aim of the
      study was to show problems connected with thorax injury. METHOD: Our
      retrospective study evaluated a group of patients with thoracic injury (diagnosis
      codes S20-S29) in the period from 1 January 2011 to 31 December 2015 who were
      treated in our Department. RESULTS: We evaluated a group of 1,697 patients with
      thoracic injury were divided into five subgroups: 1) simple contusion of the
      thorax, 2) simple rib fractures, 3) contusion of the thorax with vertebral
      fractures, 4) serial, multiple rib fractures, 5) stab and gunshot injuries of the
      thorax. Each subgroup was analyzed independently and in detail. The number of
      thoracic injuries increased steadily, year on year. More than 40% of the patients
      were older than 60 years. In the group with simple rib fractures, the authors
      found 14 cases of pneumothorax (5.1%), which was drained in only 8 cases. The
      most common complications in the serial rib fractures group included pneumothorax
      (33 cases, 20%), hemothorax (28 cases, 16.9%) and lung contusion (15 cases, 9%).
      Stabilization of the thoracic wall was performed 16 times, out of the total of 26
      multiple rib fracture cases (61.5%). CONCLUSIONS: Thorax injury is routinely
      encountered by surgeons. The authors recommend to pay particular attention not
      only to serious, but also to simple thorax injuries in very old patients, for
      instance those on anticoagulation therapy. Adequate caution also needs to be
      taken with serial rib fractures and flail chest and their treatment.Key words:
      thorax injury - rib fractures - hemothorax - pneumothorax.

PMID- 29320213
TI  - [Surprising findings during thoracic revision due to gunshot injury - a case
      report].
AB  - INTRODUCTION: Gunshot thoracic injuries are not very common in our geographical
      location, occurring most frequently in the context of criminal activity or as a
      result of suicidal behavior. CASE REPORT: The authors report the case of a
      patient who, in a suicidal attempt, caused himself a combined penetrating gunshot
      injury of the chest with laceration of the lung and a heart gunshot hole, which
      was diagnosed peroperatively. CONCLUSION: Therapy of gunshot injuries in the era
      of modern medicine should be comprehensive in multidisciplinary cooperation.Key
      words: thoracic trauma gunshot injury lung injury heart injury thoracotomy.

PMID- 29320214
TI  - [Myxoid liposarcoma localised in the peritoneal cavity case report].
AB  - INTRODUCTION: Liposarcoma is one of rare soft tissue tumours. Usually, it is
      localised in soft tissues of the extremities, can however be localised even in
      body cavities. The prognosis depends on the localisation and differentiation of
      the tumour. CASE REPORT: We present a patient indicated for surgical revision due
      to recurrence (or persistence) after previous surgery and debulking of a myxoid
      liposarcoma. Laparotomy with debulking, low anterior rectal resection with
      coloanal anastomosis, and protective ileostomy were done. No adverse events
      occurred in the postoperative period. However, another recurrence was observed in
      the subsequent follow-up. CONCLUSION: Myxoid liposarcoma is a rare tumour with a
      relatively good prognosis when radically removed; in case of intraperitoneal
      localisation it however remains a virtually unsolvable problem.Key words:
      liposarcoma - debulking recurrence.

PMID- 29320215
TI  - [Surprising histological findings on the resected specimen of the omentum due to
      a strangulated umbilical hernia].
AB  - INTRODUCTION: Gastrointestinal stromal tumor, GIST, is the most common
      mesenchymal tumor of the digestive system. It most often grows from the stomach
      or the small intestine and tends to be asymptomatic. The basic and the only
      curative therapy is an attempt at R0 resection. If the tumor is inoperable,
      metastatic or when neoadjuvant or adjuvant therapy is needed, patients are
      treated with a tyrosine kinase inhibitor - imatinib. It was discovered in 2000 on
      the basis of GIST molecular behavior. CASE REPORT: The case report describes a
      female patient who had been without any clinical symptoms for a long time until
      she presented with acute abdominal pain due to squeezed umbilical hernia. She
      underwent an acute operation, resection of the strangulated omentum and
      reconstruction of the abdominal wall. The omentum was sent for definitive
      histology. However, the pathologist described nonspecific sarcoma. A subsequent
      CT scan showed a large tumor mass in the abdominal cavity and in the small
      pelvis. A multidisciplinary team of the Motol Teaching Hospital indicated the
      patient for an attempt at radical tumor extirpation. Omentectomy, resection of
      the jejunum, hysterectomy, right adnexectomy, low anterior resection of the
      rectum and omphalectomy were performed. The result of the definitive histological
      examination was high-risk, malignant GIST, c-kit-positive, growing from the
      jejunum.Key words: GIST gastrointestinal stromal tumor KIT imatinib.

PMID- 29320216
TI  - Legibility of Text and Pictograms in Variable Message Signs: Can Single-Word
      Messages Outperform Pictograms?
AB  - OBJECTIVE: The current research shows the advantage of single-word messages in
      the particular case of variable message signs (VMSs) with a high aspect ratio.
      BACKGROUND: Early studies on traffic sign design proposed that pictorial
      information would advantage equivalent text messages in static signs. METHOD: We
      used a driving simulator to present individually 36 VMSs, showing six words
      (e.g., "congestion") and six danger signs (e.g., congestion traffic sign). In
      Experiment 1, 18 drivers read aloud the text or orally identified the pictograms
      as soon as they could correctly do it. In Experiment 2, a different sample of 18
      drivers gave a motor response, according to the meaning of the message. We
      analyzed the legibility distance and accuracy, driving performance (speed
      variability), and glance behavior. RESULTS: Our results show that single-word
      messages were associated with better performance (farther reading distances) and
      required less visual demands (fewer glances and less glancing times) than
      pictograms. CONCLUSION: As typical configurations of VMSs usually have a high
      aspect ratio, and thus allow large character heights, single-word messages can
      outperform the legibility of pictograms. However, the final advantage of text or
      pictorial messages would depend on several factors, such as the driver's
      knowledge of the language and the pictogram set, the use of single or multiple
      words, the particular design and size of critical details in letters and
      pictograms, environmental factors, and driver age. APPLICATION: Potential
      applications include the design of VMSs and other devices aimed at displaying
      text and/or pictograms with a high aspect ratio.

PMID- 29320217
TI  - Access to Health Care: Response.

PMID- 29320218
TI  - Comparison of Diabetic Foot Care to Other Diabetic Preventive Care Services.
AB  - BACKGROUND: METHODS: RESULTS: CONCLUSIONS.

PMID- 29320219
TI  - Modified Latarjet Without Capsulolabral Repair in Rugby Players With Recurrent
      Anterior Glenohumeral Instability and Significant Glenoid Bone Loss.
AB  - BACKGROUND: The optimal management of recurrent anterior shoulder instability
      with significant glenoid bone loss in high-demand collision athletes remains a
      challenge. PURPOSE: To analyze the time to return to sport, clinical outcomes,
      and recurrences following a modified Latarjet procedure without capsulolabral
      repair in rugby players with recurrent anterior shoulder instability and
      significant glenoid bone loss. STUDY DESIGN: Case series; Level of evidence, 4.
      METHODS: Between June 2008 and June 2015, 50 competitive rugby players (practice
      >2 times per week and competition during weekends) with recurrent anterior
      shoulder instability underwent operation with the modified congruent arc Latarjet
      procedure without capsulolabral repair in our institution. Cases included 18
      primary repairs and 32 revisions. Return to sports, range of motion (ROM), the
      Rowe score, a visual analog scale for pain in sport activity (VAS), and the
      Athletic Shoulder Outcome Scoring System (ASOSS) were used to assess functional
      outcomes. Recurrences were also evaluated. The postoperative bone block position
      and consolidation were assessed with computed tomography. The final analysis
      included 49 shoulders in 48 patients (31 revision cases). RESULTS: The mean
      follow-up was 48 months (range, 24-108 months) and the mean age at the time of
      operation was 22.8 years (range, 17-35 years). Forty-five patients (93.7%)
      returned to playing rugby, all at their preinjury level of play. No significant
      difference in shoulder ROM was found between preoperative and postoperative
      results. The Rowe, VAS, and ASOSS scores showed statistically significant
      improvement after operation ( P < .001). The Rowe score increased from a mean of
      39.5 points preoperatively to 94 points postoperatively ( P < .01). The VAS score
      decreased from 3.6 points preoperatively to 1.2 points postoperatively ( P <
      .01). The ASOSS score improved significantly from a mean of 44 points
      preoperatively to 89.5 points postoperatively ( P < .01). No recurrence of
      shoulder dislocation or subluxation was noted. The bone block healed in 43
      shoulders (88%). CONCLUSION: In rugby players with recurrent anterior shoulder
      instability and significant glenoid bone loss, the modified Latarjet procedure
      without capsulolabral repair produced excellent functional outcomes, with most
      athletes returning to rugby at their preinjury level of play without recurrences.

PMID- 29320221
TI  - THE FATE OF BOTRYLLUS (ASCIDIACEA) LARVAE COSETTLED WITH PARENTAL COLONIES:
      BENEFICIAL OR DELETERIOUS CONSEQUENCES?
AB  - The consequences of settlement of Botryllus larvae close to or on parental
      colonies were followed in two sets of experiments. In the first, 28 experimental
      progeny settled adjacent to 6 parents; 207 other sibling progeny served as
      controls. Four different types of interactions between parent colony and
      offspring were observed: fusion and resorption of the offspring, fusion and
      separation, tunic-to-tunic contact and separation, tunic-to-tunic contact, and
      the death of offspring. Offspring interacting with parents had significantly
      higher mortality than control offspring. Resorption was the fastest process (one
      week on average); the two "separation" processes lasted approximately two months.
      Twenty of the 21 progeny that died after interacting with parents did not grow at
      all (even after 75 days). All 7 offspring that separated from their parents grew.
      In two cases of fusion between offspring and adults, large eggs were found within
      the progeny zooids. Presumably the eggs translocated from the maternal colony
      through the connecting blood vessels. Only five progeny survived in this set of
      experiments, a phenomenon which coincided with the degeneration or the mortality
      of the parent. In the second set of experiments all 93 progeny which had settled
      on old, dead tunics of 5 parental colonies died within 8 weeks. These results
      indicate that cosettlement of offspring proximal to their parental colony is
      usually deleterious in the long term to the progeny, both when they fuse with or
      when they merely contact the parent. This phenomenon was also recorded in field
      observations. We suggest that the phenomenon of gregarious settlement of
      Botryllus larvae near their parents, although characterized by the loss of many
      progeny, is nonetheless advantageous in response to biotic interactions such as
      interspecific competition. In this view resorption may have evolved as a
      secondary process, as a result of the nature of self/nonself recognition in
      Botryllus.

PMID- 29320220
TI  - Markers of inflammation as risk predictors of lethal outcome in patients
      diagnosed with delirium.
AB  - Background/Aim: Delirium is an acute or subacute, and most frequently reversible
      syndrome of higher cortical functions disturbances that is manifested as
      generalized disorder. If not prevented, it is associated with various adverse
      outcomes. The aim of this study was to determine the connection between the
      markers of inflammation and lethal outcome in patients diagnosed with delirium,
      hospitalized in the psychiatric intensive care unit. Methods: This retrospective
      study included 120 patients hospitalized in the psychiatric intensive care unit
      in whom examination of differences in inflammation markers was done. The
      examinees have been divided into two groups: the case group of 40 patients who
      died during the hospitalization, and the control group of 80 examinees who were
      discharged with the diagnosis Post delirium status. The following variables were
      taken into account: age, gender, clinical diagnosis of infection (pneumonia and
      urinary tract infection), laboratory parameters (total of white blood cells,
      granulocytes, monocytes, C-reactive protein - CRP) and type of delirium
      (withdrawal or organic). Results: The average age of patients was 50.3 +/- 13.1
      years. The patients who survived delirium, were on the average 10.5 years younger
      than the deceased (p < 0.001). More than half (57.5%) of the deceased had
      pneumonia. There was a statistically significant correlation between pneumonia
      and lethal outcome in the patients with delirium (p < 0.001). The examinees with
      lethal outcome had significantly higher median CRP levels than the group of
      examinees who survived (75.6% +/- 54.0 vs 30.3 +/- 42.5 ng/L, p < 0.001).
      Conclusion: Aiming to better and more precise diagnostics of this complicated and
      still unclear neuropsychiatric syndrome it would be useful to consider
      introduction of more precise diagnostic algorithms in every unit of intensive
      care. That would significantly reduce the number of delirium diagnosis overlook,
      decrease complication of clinical features and would also reduce the unfavorable
      outcome rate, therefore the total cost of treatment.

PMID- 29320222
TI  - VARIABILITY IN FLASH CHARACTERISTICS OF A BIOLUMINESCENT COPEPOD.
AB  - Bioluminescence of the copepod, Pleuromamma xiphias, was investigated with an
      optical multichannel analyzer(OMA) to measure emission spectra, an integrating
      sphere-photon counting detector system to determine flash kinetics and quantum
      emission, and an ISIT video system to image spatial patterns of emission. Light
      emission was in the blue spectral region, with maximum emission at approximately
      492 nm. Spectral waveforms were unimodal, or bimodal with the secondary peak at
      472 nm. Flashes in response to a single stimulus consisted of two components: a
      fast component attaining maximum intensity in under 100 ms, and a slow element
      which peaked after 600 ms. The fast component originated from thoracic and
      abdominal light organs while the slow component represented a large expulsion of
      luminescent material from the abdominal organ only. Both components exhibited
      first order exponential decay although the decay rate of the fast component was
      approximately one order of magnitude greater. The typical flash response to a
      single stimulus exhibited a response latency of 30 ms, initial rise time of 87
      ms, duration of 2.4 s, and quantum emission of 1.4 x 1010 photons flash-1.
      Quantum emission increased with increasing stimulus strength. Both response
      waveform and total quantum emission were affected by the frequency of electrical
      stimuli. Stimulation at 1 Hz generated the greatest luminescence, averaging 1.1 x
      1011 photons response-1 for 11 s emissions. Higher rates of stimulation decreased
      total quantum emission and response episode duration, and resulted in greater
      temporal summation of the emission waveform. Variability in flash characteristics
      due to electrical stimulation suggests a versatility of luminescent displays in
      situ.

PMID- 29320223
TI  - QUANTITATIVE ESTIMATION OF MOVEMENT OF AN AMINO ACID FROM HOST TO CHLORELLA
      SYMBIONTS IN GREEN HYDRA.
AB  - Washing symbiotic Chlorella algae freshly isolated from green hydra with 0.05%
      sodium dodecyl sulphate was shown to remove virtually all contaminating host
      material, previously a severe constraint in quantifying movement of metabolites
      from host to symbionts. When brine shrimp labelled with 3H-leucine were fed to
      hydra in symbiosis either with the native strain of Chlorella (E/E hydra) or two
      strains cultured from Paramecium bursaria (E/3N and E/NC hydra), it was found
      that after 24 h 3-4% of the total radioactivity retained by the symbiosis was
      present in the algae. Analysis of the free amino acid pool of symbiotic algae
      from E/E hydra showed that over 70% of the radioactivity was associated with
      leucine, and significant amounts of radioactivity were retained by these algae
      for at least five days following a single feeding with radioactive brine shrimp.
      In both E/E and E/NC hydra, the amount of radioactivity per unit protein was
      considerably less in the symbionts than in the host, suggesting that access to
      host amino acid pools were limited. These results are discussed in terms of the
      possible role and regulatory significance of amino acids as a nitrogen source to
      symbiotic Chlorella, and of the cost to the host in maintaining the symbiosis.

PMID- 29320224
TI  - NEURONAL CONTROL OF CILIARY LOCOMOTION IN A GASTROPOD VELIGER (CALLIOSTOMA).
AB  - Intracellular recordings from pre-oral ciliated cells of competent Calliostoma
      ligatum veligers were used to demonstrate the mechanisms of neuronal control of
      ciliary locomotion. During normal ciliary beating at 5-7 Hz, the membrane
      potential shows no oscillations or spiking activity. It remains at a resting
      potential of about -60 mV. Depolarization from resting potential is due to
      excitatory input from the CNS and, depending upon the kind of input, veligers
      appear to show two types of locomotory behavior. In one type, normal ciliary
      beating is periodically interrupted by rapid, velum-wide ciliary arrests. These
      arrests are caused by a propagated, Ca++-dependent action potential in the pre
      oral ciliated cells. The second type is characterized by either a velum-wide or
      local slowing of normal ciliary beating, and appears to result from a slow
      depolarization of the ciliated cell membrane. Pre-oral ciliated cells are
      electrically coupled to each other. This property may ensure the synchrony of
      velum-wide ciliary arrests or differential velar slowing of ciliary beating.
      These findings demonstrate some of the mechanisms ofthe fine control veligers
      possess over their locomotory and feeding behavior.

PMID- 29320225
TI  - FEEDING BEHAVIOR IN HYDRA. I. EFFECTS OF ARTEMIA HOMOGENATE ON NEMATOCYST
      DISCHARGE.
AB  - Inhibition of desmoneme and stenotele nematocyst discharge occurs when Hydra
      attenuata are fed to repletion. Inhibition can be induced by the application of
      prey homogenates in the external medium. The onset of inhibition is relatively
      rapid (<30 s) while the release from inhibition is much slower (>20 min).
      Inhibition is concentration-depedent. Gel chromatography separation of homogenate
      shows that the inhibitory substance(s) have a molecular weight greater than 5000.
      These substances cause the strongest stenotele inhibition and are least effective
      in activating the feeding reflex (mouth opening and tentacle concerts) which is
      caused by smaller molecular weight substances. The receptor sites for the
      inhibitory substance(s) are located on the external surface of the hydra
      tentacle. Accumulation of prey substances may be the mechanism by which stenotele
      discharge is inhibited when hydra are fed to repletion.

PMID- 29320226
TI  - THE EFFECTS OF SALINITY STRESS ON THE RATES OF AEROBIC RESPIRATION AND
      PHOTOSYNTHESIS IN THE HERMATYPIC CORAL SIDERASTREA SIDEREA.
AB  - Corals are reputed to have low tolerance to salinity fluctuations. Yet the
      scleractinian coral Siderastrea siderea commonly inhabits reef zones and
      nearshore areas that experience salinity fluctuations of 5 to l0%. Small colonies
      of this species were subjected to both long-term and sudden decreases or
      increases in salinity. Their rates of aerobic respiration and photosynthesis,
      measured as changes in oxygen concentration, were followed for up to 144 hours
      after the sudden changes. Normal salinities of coastal waters near Panacea,
      Florida, are 28 to 30% but S. siderea was able to acclimate to 42% when salinity
      was increased slowly over a 30-day period. Neither respiratory nor photosynthetic
      rates of S. siderea were affected by changes in salinity of less than 10% above
      or below the acclimation salinity. Greater changes in salinity (either up or
      down) caused decreases in respiratory and photosynthetic rates proportional to
      the magnitude of the salinity change. Decreases in chborophyll per algal cell and
      in assimilation number were associated with and possibly responsible for some of
      the decreases in photosynthetic rates. These results show that S. siderea is able
      to withstand sudden and prolonged, environmentally realistic changes in salinity
      without measurable whole-animal effects. Further studies are needed to determine
      whether this species is remarkable in its ability to tolerate salinity change, or
      whether reef corals are more tolerant to salinity change than is generally
      believed.

PMID- 29320227
TI  - UPSTREAM AND DOWNSTREAM CAPTURE DURING SUSPENSION FEEDING BY OLIGOMETRA
      SERRIPINNA (ECHINODERMATA: CRINOIDEA) UNDER SURGE CONDITIONS.
AB  - The crinoid Oligometra serripinna is a suspension feeder that usually experiences
      unidirectional tidal currents from which it extracts food particles by downstream
      capture (i.e., while the food grooves face downcurrent). However, near slack
      tide, wave surge may cause brief current reversals, each lasting about 2 s at
      roughly 10 s intervals. To test if a crinoid can engage in upstream capture
      (i.e., while the food grooves face upcurrent) during brief current reversals, we
      approximated these surge conditions in a laboratory flume. In the laboratory, as
      in the field, the crinoid oriented its food grooves downstream with respect to
      the predominant current, and the body posture did not change during the brief
      intervals of reversed flow. Brine shrimp cysts were added to the flume, and video
      recordings were made of the crinoid capturing these particles. Under surge
      conditions, the crinoid (1) captured 16.2% of the approaching particles while its
      food grooves faced downstream and (2) captured 8.0% of the approaching particles
      while its food grooves faced upstream. Thus O. serripinna used its filter both
      for upstream capture and for downstream capture, although the former was only
      about half as efficient as the latter.

PMID- 29320228
TI  - EELGRASS WASTING DISEASE: CAUSE AND RECURRENCE OF A MARINE EPIDEMIC.
AB  - Eelgrass populations are currently infected with a disease that produces symptoms
      and epidemiology reminiscent of the famous eelgrass wasting disease of the 1930s.
      This disease virtually eliminated eelgrass (Zostera marina L.) in the North
      Atlantic for three decades. For 50 years scientists have speculated about the
      cause of the 1930s eelgrass decline. We have now proven that the causal organism
      of the present epidemic is a pathogenic strain of Labyrinthula, which was
      suspected, but never conclusively shown to cause the 1930s wasting disease. We
      have isolated the infectious form of Labyrinthula from eelgrass from Maine to
      North Carolina on the Atlantic coast, and from Puget Sound on the Pacific coast;
      disease-related dieoffs of eelgrass beds are confirmed in Maine, New Hampshire,
      and Massachusetts.

PMID- 29320229
TI  - ABSTRACTS OF PAPERS PRESENTED AT THE MARINE BIOLOGICAL LABORATORY: NORTHEASTERN
      REGIONAL CONFERENCE ON DEVELOPMENTAL BIOLOGY.

PMID- 29320230
TI  - PHYSIOLOGICAL AND BIOCHEMICAL INVESTIGATIONS OF THE EGG JELLY RELEASE IN PENAEUS
      AZTECUS.
AB  - Following contact with seawater, Penaeus aztecus ova undergo a massive release of
      extracortical jelly precursor material which is transformed into a layer of jelly
      like material surrounding the ova. Release and dissipation of the precursors can
      be irreversibly inhibited by the protease inhibitors N-a-p-tosyl-L-lysine
      chloromethyl ketone and soybean trypsin inhibitor, implicating trypsin-like
      proteases in the process. Treatment with the less-specific enzyme inhibitor
      phenylmethyl sulfonyl fluoride also irreversibly inhibits the release of the
      cortical material. Jelly precursor in whole mature ovaries stain positive with
      PAS. Staining with alcian blue reveals acid mucopolysaccharides in the investment
      coat of the ova but not in the jelly precursors. Precursors isolated from whole
      mature ovaries are approximately 25-30% carbohydrate (anthrone sulfuric acid
      reaction) and 70-75% protein (Lowry's and Bradford's protein determinations). No
      sialic acids are detected in the isolates (thiobarbituric acid assay). Trypsin is
      effective in dissipating the precursor isolates. Amino acid analysis reveals high
      ratios of cysteic acid. Significant biochemical differences between P. aztecus
      egg jelly material and sea urchin egg jelly are discussed.

PMID- 29320231
TI  - QUANTITATIVE GENETICS OF JUVENILE GROWTH AND SHAPE IN THE MUD CRAB EURYPANOPEUS
      DEPRESSUS 1.
AB  - Rates of growth and development were measured for the first six molts following
      the crab 1 stage in the mud crab Eurypanopeus depressus. The genetic contribution
      to variation in growth rate, development rate, and shape was determined for each
      molt interval. Genetic variation in growth rate, measured as increases in both
      width and length, was evident at most molt intervals. There were also significant
      genetic effects upon the intermolt interval. Growth rates for each molt interval,
      calculated on a daily basis to remove the interaction between growth rate and
      development rate also showed genetic variation. There was no evidence that
      genetic variation in these parameters changed during early juvenile development;
      there were substantial levels of genetic variation in growth rate at most
      ontological stages. Despite high levels of genetic variation for growth rate in
      dimensions of the carapace, there was no evidence of genetic variation in shape.
      This analysis does not provide a quantitative estimate of the levels of genetic
      variance for these traits but does indicate that the magnitude of this source of
      variance must be very significant.

PMID- 29320232
TI  - Barriers to the Adoption of Wearable Sensors in the Workplace: A Survey of
      Occupational Safety and Health Professionals.
AB  - OBJECTIVE: To gather information on the (a) types of wearable sensors,
      particularly personal activity monitors, currently used by occupational safety
      and health (OSH) professionals; (b) potential benefits of using such technologies
      in the workplace; and (c) perceived barriers preventing the widespread adoption
      of wearable sensors in industry. BACKGROUND: Wearable sensors are increasingly
      being promoted as a means to improve employee health and well-being, and there is
      mounting evidence supporting their use as exposure assessment and personal health
      tools. Despite this, many workplaces have been hesitant to adopt these
      technologies. METHODS: An electronic survey was emailed to 28,428 registered
      members of the American Society of Safety Engineers (ASSE) and 1,302
      professionals certified by the Board of Certification in Professional Ergonomics
      (BCPE). RESULTS: A total of 952 valid responses were returned. Over half of
      respondents described being in favor of using wearable sensors to track OSH
      related risk factors and relevant exposure metrics at their respective
      workplaces. However, barriers including concerns regarding employee
      privacy/confidentiality of collected data, employee compliance, sensor
      durability, the cost/benefit ratio of using wearables, and good manufacturing
      practice requirements were described as challenges precluding adoption.
      CONCLUSION: The broad adoption of wearable technologies appears to depend largely
      on the scientific community's ability to successfully address the identified
      barriers. APPLICATION: Investigators may use the information provided to develop
      research studies that better address OSH practitioner concerns and help
      technology developers operationalize wearable sensors to improve employee health
      and well-being.

PMID- 29320233
TI  - Antibacterial Activities of Hibiscus sabdariffa Extracts and Chemical Sanitizers
      Directly on Green Leaves Contaminated with Foodborne Pathogens.
AB  - Leafy greens have been associated with foodborne disease outbreaks in different
      countries. To decrease microbial contamination of leafy greens, chemical agents
      are commonly used; however, a number of studies have shown these agents to have
      limited antimicrobial effect against pathogenic bacteria on vegetables. The
      objective of this study was to compare the antibacterial effect of Hibiscus
      sabdariffa calyx extracts (water, methanol, acetone, and ethyl acetate), sodium
      hypochlorite, acetic acid, and colloidal silver against foodborne bacteria on
      leafy greens. Thirteen foodborne bacteria were used in the study: Listeria
      monocytogenes, Shigella flexneri, Salmonella serotypes Typhimurium Typhi, and
      Montevideo, Staphylococcus aureus, Escherichia coli O157:H7, five E. coli
      pathotypes (Shiga toxin-producing, enteropathogenic, enterotoxigenic,
      enteroinvasive, and enteroaggregative), and Vibrio cholerae O1. Each foodborne
      bacterium was separately inoculated on romaine lettuce, spinach, and coriander
      leaves. Separately, contaminated leafy greens were immersed in four hibiscus
      extracts and in sanitizers for 5 min. Next, green leaves were washed with sterile
      tap water. Separately, each green leaf was placed in a bag that contained 0.1%
      sterile peptone water and was rubbed for 2 min. Counts were done by plate count
      using appropriate dilutions (in sterile peptone water) of the bacterial
      suspensions spread on Trypticase soy agar plates and incubated at 35 +/- 2
      degrees C for 48 h. Statistically significant differences ( P < 0.05) were
      calculated with an analysis of variance and Duncan's test. All 13 foodborne
      bacteria attached to leafy greens. Roselle calyx extracts caused a significantly
      greater reduction ( P < 0.05) in concentration of all foodborne bacteria on
      contaminated romaine lettuce, spinach, and coriander than did the sodium
      hypochlorite, colloidal silver, and acetic acid. Dry roselle calyx extracts may
      potentially be a useful addition to disinfection procedures for romaine lettuce,
      spinach, and coriander.

PMID- 29320234
TI  - Influence of Soap Characteristics and Food Service Facility Type on the Degree of
      Bacterial Contamination of Open, Refillable Bulk Soaps.
AB  - Concern has been raised regarding the public health risks from refillable bulk
      soap dispensers because they provide an environment for potentially pathogenic
      bacteria to grow. This study surveyed the microbial quality of open refillable
      bulk soap in four different food establishment types in three states. Two hundred
      ninety-six samples of bulk soap were collected from food service establishments
      in Arizona, New Jersey, and Ohio. Samples were tested for total heterotrophic
      viable bacteria, Pseudomonas, coliforms and Escherichia coli, and Salmonella.
      Bacteria were screened for antibiotic resistance. The pH, solids content, and
      water activity of all soap samples were measured. Samples were assayed for the
      presence of the common antibacterial agents triclosan and parachlorometaxylenol.
      More than 85% of the soap samples tested contained no detectable microorganisms,
      but when a sample contained any detectable microorganisms, it was most likely
      contaminated at a very high level (~7 log CFU/mL). Microorganisms detected in
      contaminated soap included Klebsiella oxytoca, Serratia liquefaciens, Shigella
      sonnei, Enterobacter gergoviae, Serratia odorifera, and Enterobacter cloacae.
      Twenty-three samples contained antibiotic-resistant organisms, some of which were
      resistant to two or more antibiotics. Every sample containing less than 4% solids
      had some detectable level of bacteria, whereas no samples with greater than 14%
      solids had detectable bacteria. This finding suggests the use of dilution and/or
      low-cost formulations as a cause of bacterial growth. There was a statistically
      significant difference ( P = 0.0035) between the fraction of bacteria-positive
      samples with no detected antimicrobial agent (17%) and those containing an
      antimicrobial agent (7%). Fast food operations and grocery stores were more
      likely to have detectable bacteria in bulk-soap samples compared with convenience
      stores ( P < 0.05). Our findings underscore the risk to public health from use of
      refillable bulk-soap dispensers in food service establishments.

PMID- 29320236
TI  - ERRATUM.
AB  - THE BIOLOGICAL BULLETIN, Volume 166, Number 3, Page 529 The following correction
      should be made in the paper by Chizuko Obata and Shin-Ichi Nemoto entitled,
      Artificial parthenogenesis is in starfish eggs: production of parthenogenetic
      development through suppression of polar body formation by methlxanthines (1984,
      Biol. Bull. 166: 525-536): the scale bar in A of Figure 4 should read 150 um.
      Thus the last sentence of the legend should read: Bar in A representing 150 um is
      common to A through F.

PMID- 29320235
TI  - A Limited Survey of Metal Content in Blue Jack Mackerel ( Trachurus picturatus)
      Obtained from Markets in the Canary Islands.
AB  - The levels of 20 metals (aluminum, boron, barium, calcium, cadmium, cobalt,
      chromium, copper, iron, potassium, lithium, magnesium, manganese, molybdenum,
      sodium, nickel, lead, strontium, vanadium, and zinc) were analyzed in muscle and
      liver tissue of Trachurus picturatus marketed in the Canary Islands (Spain) by
      using inductively coupled plasma optical emission spectrometry. In the liver
      samples, the mean concentrations in milligrams per kilogram wet weight (wt) of Al
      (14.7), B (0.99), Ba (1.64), Ca (314), Cd (2.52), Co (0.15), Cu (4.07), Fe (106),
      Li (3.89), Mn (0.85), Mo (0.16), Na (1510), Ni (0.51), Pb (0.36), Sr (3.54), V
      (0.78), and Zn (23.13) were higher than those detected in the muscle samples in
      milligrams per killogram wet wt, which were as follows: Al (8.76), B (0.07), Ba
      (0.30), Ca (210), Cd (0.01), Co (0.01), Cu (1.51 ), Fe (7.33), Li (1.08), Mn
      (0.12), Mo (0.01), Na (697), Ni (0.11), Pb (0.04), Sr (1.45), V (0.01), and Zn
      (4.69). The mean concentrations of Cr, K, and Mg (0.14, 1,904, and 243 mg/kg wet
      wt, respectively) were higher in muscle than in liver (0.05, 1,333 and 236 mg/kg
      wet wt, respectively). The mean concentrations of Cd and Pb (0.01 and 0.04 mg/kg
      wet wt) in muscle did not exceed the maximum limits established by a European
      Commission regulation (0.1 mg of Cd/kg and 0.3 mg of Pb/kg, respectively).
      Considering a mean daily consumption of fish muscle for the adult population of
      31.9 g/day published in the report on food consumption by the Spanish Ministry of
      Agriculture and Fisheries, Food and Environment, Mg made the highest
      contributions to the intake (2.58% for adult women of 60 kg and 2.22% for men of
      70 kg), and the estimated intakes of Al (0.35 to 0.46 mg/day), Cd (0.55 to 0.74
      mg/day) and Pb (1.66 to 5.53 mg/day) were below the respective established
      tolerable intakes. In conclusion, the results of this study show that the
      consumption of muscle from this benthopelagic species can be considered safe in
      terms of maximum legal limits, while consumption of liver is discouraged as a
      major source of exposure to toxic metals, such as Al, Cd, and Pb.

PMID- 29320238
TI  - THE PREVENTION OF POLYSPERMIC FERTILIZATION IN SEA URCHINS.

PMID- 29320237
TI  - LABORATORY STUDIES OF FEEDING AND MATING IN SPECIES OF CARCINONEMERTES (NEMERTEA:
      HOPLONEMERTEA).
AB  - Details of the suctorial feeding behavior of some species of Carcinonemertes on
      crab eggs are described. Under laboratory conditions juvenile and male worms ate
      an average of 0.6-0.7 crab egg/day. Females ate 2-3 eggs/day. Laboratory feeding
      rates of worms from different hosts were similar when worms were fed eggs of the
      same host. No worms ate lobster eggs. Worms grown under laboratory conditions
      tended to be smaller than similar-aged worms found on hosts. Female worms fed
      natural host eggs or eggs of unnatural hosts started laying egg strings in a
      variable number of days. More variability in timing of egg production was
      observed within a worm species than between species when fed on the same host's
      eggs. Mating behavior is described for the first time for a species of
      Carcinonemertes.

PMID- 29320239
TI  - MORPHOLOGICAL OBSERVATIONS AND MICROSPECTROPHOTOMETRIC DATA FROM PHOTORECEPTORS
      IN THE RETINA OF THE SEA RAVEN, HEMITRIPTERUS AMERICANUS.
AB  - A histological survey of the retinas of some fishes has revealed an unusual cone
      formation. We repeatedly find these unusual triple cones in 10% of the retinas
      reviewed. To obtain further information about these photoreceptors, the sea
      raven, whose retina is known to contain them, was chosen for further study.
      Microspectrophotometric measurements were made to determine the peak absorbance
      of the visual pigment contained in the three individual outer segments. We report
      here the results of measurements made on triple cones found in the retina of the
      sea raven, Hemitripterus americanus.

PMID- 29320240
TI  - FINE STRUCTURE AND VITAL STAINING OF OSPHRADIUM OF THE SOUTHERN OYSTER DRILL,
      THAIS HAEMASTOMA CANALICULATA (GRAY) (PROSOBRANCHIA: MURICIDAE).
AB  - The morphology of the osphradium of Thais haemastoma canaliculata (Gray) was
      examined using light microscopy, SEM, and TEM. The osphradium is composed of
      approximately 150-200 lamellae, each of which is divided into two distinct
      regions by a groove situated parallel to the dorsal edge of the organ. The dorsal
      one-fourth of each lamella is covered by dense cilia that are assumed to generate
      water currents about the osphradium. Ciliary tufts, located in small depressions,
      and numerous secretory cells are distributed uniformly on the ventral three
      fourths of the lamellae. A thin tract of cilia borders the ventral edge of each
      lamella. The overall cellular organization is less complex than has been reported
      previously in other marine prosobranchs. Selective staining of putative
      chemoreceptors was performed using Procion Brilliant Yellow. Individual cells in
      the ventral region and the ventral edge of each lamella were Procion-positive.
      Results of this study suggest that ventral interlamellar regions and the ventral
      edge of each lamella are chemosensory regions, while the dorsal portion of each
      lamella is indifferent epithelium.

PMID- 29320241
TI  - CHEMOAUTOTROPHIC SYMBIONTS IN THE BIVALVE LUCINA FLORIDANA FROM SEAGRASS BEDS.
AB  - Enzymatic and histological evidence suggest that the eulamellibranch bivalve
      Lucina fioridana possesses bacterial endosymbionts capable of a chemoautotrophic
      metabolism. Dense populations of L. floridana (83 +/- 11 per m2; 95% CI, n = 33)
      are found closely associated with the O2-releasing root systems of seagrasses in
      sulfiderich sediments; the sandy sediments of both Thalassia and Ruppia beds
      contain 1.67 +/- 0.3 1 mM (95% CI, n = 13) and 2.49 +/- 0.55 mM (95% CI, n = 13)
      sulfide, respectively. Both transmission electron microscopy of gill tissue and
      scanning electron microscopy of freeze-fractured gills reveal numerous rod-shaped
      procaryotic inclusions in vacuoles of large, eucaryotic cells ("bacteriocytes")
      located deeply within demibranch cross sections; no such inclusions are seen in
      the ciliated gill epitheium which is rich in mitochondria. Activities of ribulose
      1,5-bisphosphate carboxylase (RuBPCase), phosphoribulokinase, APS reductase, ATP
      sulfurylase, and nitrite reductase have been measured and partially characterized
      in homogenates of fresh gill tissue. Light microscopy reveals numerous
      aggregations of pigmented granules localized to the interior of the gill in
      association with the bacteriocytes. Histochemical staining demonstrates the
      presence of iron in these granules, consistent with the idea that their
      composition, in part, may be respiratory pigment and/or iron-containing
      cytochromes. Energy dispersive X-ray analysis reveals sulfur as a dominant
      inorganic element in the gill tissue. Based on abundance data of L. fioridana and
      in vitro levels of RuBPCase (half-maximal velocity) this bivalve could
      potentially contribute 336 +/- 96 g C/m2/year (95% CI) to the gross carbon
      fixation of seagrass beds.

PMID- 29320242
TI  - CHEMOSENSORY RESPONSES TO AMINO ACIDS AND CERTAIN AMINES BY THE CILIATE
      TETRAHYMENA: A FLAT CAPILLARY ASSAY.
AB  - An assay for chemosensory responses by the ciliate Tetrahymena thermophila is
      described that uses glass capillaries with a rectangular cross-section (inner
      dimensions, 20 x 2 x 0.2 mm). These have optical and geometrical properties
      permitting convenient observation of cell behavior within the capillaries. Washed
      cells, starved for 12 h, accumulated preferentially in capillaries containing L
      methionine, L-leucine, L-cysteine, L-histidine, L-histamine, cimetidine,
      agmatine, and berenil at concentrations of 10-3 M or less. They avoided
      capillaries containing tripelennamine, diphenhydramine, and pentamidine at these
      concentrations. It is argued that the actual response thresholds are much lower
      than the concentrations put into the capillaries, since cells respond to the
      gradient of the diffusing chemical. L-Isoleucine, itself inert, blocked the
      response to L-leucine but not to L-methionine, L-cysteine, or L-histidine. L
      Ethionine and 1-homocysteine caused accumulation but not L-cysteine or DL
      cystathionine. L-Cystine did not block the response to L-cysteine. Cells
      accelerated when entering a capillary where accumulation occurred. On reaching
      the interior they swam more slowly and uniformly, and with fewer turns or stops
      than in control capillaries lacking the chemical signal, or when outside of the
      capillaries. Cells were inhibited from leaving both control and test capillaries,
      possibly because of accumulated wastes or secretions in the surrounding medium.

PMID- 29320243
TI  - THE FMRFamide-LIKE NEUROPEPTIDE OF APLYSIA IS FMRFamide.
AB  - The head ganglia from 350 Aplysia brasiliana were extracted and purified by gel
      (Sephadex G-15) and cation exchange (CM-Sephadex) chromatography; the fractions
      were examined with radioimmunoassays (RIA) for the molluscan neuropeptides,
      FMRFamide and SCPB. Immunoreactive (ir-) FMRFamide (but not ir-SCPB) coeluted
      with authentic FMRFamide from both chromatographic columns. The amino acid
      composition of the purified peptide was: Phe 2: Arg 1: Met 1. Digestion of
      purified ir-FMRFamide with carboxypeptidase Y indicated that the four residues
      were in the same sequence as occurs in FMRFamide. The dose-response curves for
      purified and synthetic FMRFamide on the radula protractor muscle of Busycon
      contrarium were coincident, as were their inhibition binding curves in the
      FMRFamide RIA. The highest concentrations of ir-FMRFamide were in the pedal and
      pleural ganglia; but SCPB was concentrated in the buccal ganglion. Synthetic SCPB
      has no effect on the radula protractor muscle of Busycon or the isolated heart of
      Mercenaria. In conclusion, the FMRFamide-like peptide in the gastropod Aplysia is
      FMRFamide, so this peptide has now been identified in two molluscan classes.
      Moreover, the proposed structural relationship between FMRFamide and SCPB is
      fortuitous, and these two peptides should have different physiological functions
      in Aplysia.

PMID- 29320244
TI  - ABSTRACTS OF PAPERS PRESENTED AT THE GENERAL SCIENTIFIC MEETINGS OF THE MARINE
      BIOLOGICAL LABORATORY.

PMID- 29320245
TI  - DIRECT ACCESS OF IONS TO THE SQUID STELLATE GANGLION GIANT SYNAPSE BY AORTIC
      PERFUSION: EFFECTS OF CALCIUM-FREE MEDIUM, LANTHANUM, AND CADMIUM.
AB  - The giant synapse in the squid stellate ganglion has served as a model in the
      understanding of normal synaptic transmission, but has not been used extensively
      in the study of changes in external ion concentrations or pharmacological agents.
      This anomaly is due primarily to the substantial diffusion barrier that exists
      between the synapse and the bathing medium. The present study describes a
      technique for the rapid introduction of substances into the synapse by perfusion
      through the arterial blood supply that improves access by at least 50-fold. This
      is demonstrated by treatments known to block the Ca2+ activated release of
      transmitter from the nerve terminal: Ca2+-free medium, La3+, and Cd2+. Whereas
      such treatments take 20 minutes to 3 hours to block transmitter release with bath
      application, with perfusion they act within a few seconds. The excitatory
      postsynaptic potential (EPSP) is reduced below action potential threshold in 5 to
      22 seconds, and disappears completely in less than a minute. In addition, the use
      of pressurized O2 to drive the perfusate through the preparation eliminates the
      need for superfusion with O2 and aids in the long term maintenance of the
      ganglion. This study confirms the important role of Ca2+ in the release of
      transmitter at the giant synapse, and opens up this neurobiologically important
      preparation for ionic and pharmacologic evaluation.

PMID- 29320246
TI  - TRANSFER OF NEMERTEAN EGG PREDATORS DURING HOST MOLTING AND COPULATION.
AB  - Juvenile nemertean egg predators were able to efficiently transfer from the
      premolt cuticle to the postmolt cuticle of male and female crabs when the host
      molted. These worms also efficiently transferred from male to female hosts at
      copulation. The synchronized responses of the nemertean worms to host physiology
      and behavior dramatically concentrate the nemertean population on the sole food
      source required for worm reproduction: crab eggs. The efficient location of
      reproductive crabs by juvenile worms increased the likelihood that these worms
      can have significant effects on crab fisheries when worm population density is
      high.

PMID- 29320247
TI  - DAILY BUDGETS OF PHOTOSYNTHETICALLY FIXED CARBON IN SYMBIOTIC ZOANTHIDS.
AB  - We tested the hypothesis that some zoanthids are able to meet a portion of their
      daily respiratory carbon requirement with photosynthetic carbon from symbiotic
      algal cells (= zooxanthellae). A daily budget was constructed for carbon (C)
      photosynthetically fixed by zooxanthellae of the Bermuda zoanthids Zoanthus
      sociatus and Palythoa variabilis. Zooxanthellae have an average net
      photosynthetic C fixation of 7.48 and 15.56 ugC.polyp-1.day-1 for Z. sociatus and
      P. variabilis respectively. The C-specific growth rate (uc) was 0.215.day-1 for
      Z. sociatus and 0.152.day-1 for P. variabilis. The specific growth rate (u) of
      zooxanthellae in the zoanthids was measured to be 0.011 and 0.017.day-1 for Z.
      sociatus and P. variabilis zooxanthellae respectively. Z. sociatus zooxanthellae
      translocated 95.1% of the C assimilated in photosynthesis, while P. variabilis
      zooxanthellae translocated 88.8% of their fixed C. As the animal tissue of a
      polyp of Z. sociatus required 14.75 ugC.day-1 for respiration, and one of P.
      variabiis required 105.54 ugC.day-1, the contribution of zooxanthellae to animal
      respiration (CZAR) was 48.2% for Z. sociatus and 13.1% for P. variabilis.

PMID- 29320248
TI  - CHEMICAL MEDIATION OF APPETITIVE FEEDING IN A MARINE DECAPOD CRUSTACEAN: THE
      IMPORTANCE OF SUPPRESSION AND SYNERGISM.
AB  - The California spiny lobster, Panulirus interruptus, failed to exhibit appetitive
      feeding or locomotion in response to a low molecular weight fraction (< 1000
      daltons) prepared from a sea water extract of muscle from abalone, a natural
      prey. This lack of response was caused by chemical suppressants, rather than by
      lack of stimulatory compounds. Excitatory responses were induced by single, low
      molecular weight compounds, but these responses were inhibited by suppressants
      which occur naturally in the muscle fraction. Amino and organic acids were found
      highly stimulatory to lobsters, but nucleotides and sugars were not. A mixture of
      monocarboxylic amino acids and dicarboxylic organic acids was much more effective
      in elliciting behavior than either of the constituents tested alone, at the same
      overall concentration. Mixtures which combined either ammonium or urea with amino
      or organic acids significantly reduced behavioral activity caused by these latter
      substances. Results indicate that tests of single chemicals cannot always
      reliably predict the stimulatory properties of solutions, combining even as few
      as two or more compounds. The stimulatory properties of complex odorants,
      including prey extracts, are best assessed by fractionating and then combining
      and testing the fractions in bioassays of factorial design.

PMID- 29320249
TI  - MICROSCOPIC OBSERVATIONS OF CRYPTIC POLAR BODY PRODUCTION AND SPIRALIAN
      ORGANIZATION IN ThE EGG OF ILYANASSA OBSOLETA.
AB  - Light microscopy of semi-thin sections and scanning electron microscopy reveal a
      pit at the animal pole of Ilyanassa obsoleta during Meiosis I. The incipient
      polar body is within the pit. Sections show the spindle at an oblique angle to
      the egg axis, an early expression of the spiralian organization of this egg.
      Surface changes on the incipient polar body are similar to those described by
      others for the polar lobe of Nassarius reticulatus.

PMID- 29320250
TI  - REPRODUCTION, EMBRYONIC ENERGETICS, AND THE MATERNAL-FETAL RELATIONSHIP IN THE
      VIVIPAROUS GENUS SEBASTES (PISCES: SCORPAENIDAE).
AB  - Reproduction in the scorpaenid genus Sebastes has been characterized as primitive
      ovoviviparity. In the black rockfish, S. melanops, egg size is small (0.8 mm),
      but the gestation period is 37 days and larvae at birth are well developed, with
      a remnant of yolk and the ability to initiate feeding. To test the hypothesis
      that this species is viviparous with additional maternal nutrition, we studied
      embryonic energetics and morphology. Catabolism during development utilized 64%
      of the yolk energy, resulting in a maximum yolk utilization efficiency of 36%,
      similar to oviparous fishes. Calorimetry, however, demonstrates that 81% of the
      initial yolk energy is present at birth. Thus approximately 70% of the catabolic
      energy is contributed by the maternal system during gestation. Microscopic
      analysis of embryonic epidermis suggests no specializations for nutrient uptake.
      Histological observations, however, reveal that the hindgut is functional
      approximately 22-25 days after fertilization. Thus, we suggest that nutrition
      occurs through consumption and assimilation of ovarian fluid. Reproductive modes
      in the Scorpaenidae have apparently evolved from simple oviparity in seven of
      eight subfamilies, to lecithotrophic viviparity in more primitive members of the
      subfamily Sebastinae, through matrotrophic viviparity in Sebastes. This pattern
      involved progressively longer retention of embryos until after organogenesis and
      functional differentiation of the gut, facilitating this rather primitive form of
      embryonic nutrition among matrotrophic viviparous species.

PMID- 29320252
TI  - PROTEIN SYNTHESIS IN NORMAL AND LOBELESS GASTRULAE OF ILYANASSA OBSOLETA.
AB  - Several hundred proteins synthesized by normal and lobeless Ilyanassa gastrulae
      were identified by the two-dimensional electrophoresis of polypeptides labeled in
      vivo with 35S-methionine. Acidic proteins were separated in the first dimension
      by isoelectric focusing and basic proteins by non-equilibrium pH gradient
      electrophoresis (NEPHGE). No qualitative differences were detected among either
      the acidic or basic polypeptides produced by normal or lobeless gastrulae. These
      findings show, for those peptides detected in this analysis, that (1) the stage
      specific changes in protein synthesis that occur in Ilyanassa embryos by
      gastrulation (Collier and McCarthy, 1981) are not polar lobe dependent, and (2)
      the polar lobe cytoplasm does not qualitatively affect the expression of either
      maternal or embryonic mRNAs during gastrulation.

PMID- 29320251
TI  - PROLINE BETAINE: A UNIQUE OSMOLYTE IN AN EXTREMELY EURYHALINE OSMOCONFORMER.
AB  - The extremely euryhaline mollusc, Elysia chiorotica, does not utilize
      intracellular free amino acids for cell volume regulation during osmotic stress.
      Instead, Elysia utilizes an osmolyte previously unknown from animals, proline
      betaine. Although proline betaine occurs in some plants and Elysia forms a
      symbiosis with an algae, the proline betaine in Elysia seems to be a product of
      the animal.

PMID- 29320253
TI  - FORMATION, ORGANIZATION, AND COMPOSITION OF THE EGG CAPSULE OF THE MARINE
      GASTROPOD, ILYANASSA OBSOLETA.
AB  - Embryos of the marine mud snail Ilyanassa obsoleta undergo early development
      within an egg capsule. After about a week of encapsulation, embryos hatch by
      releasing a chemical substance that removes the plug found at the apex of a
      capsule. However, the mechanism of action of this hatching substance remains
      poorly understood. To study how the hatching substance functions, we examined the
      composition of the egg capsule, particularly the plug region, to determine what
      the "substrate" of the hatching substance might be. We have also examined the
      formation and organization of the egg capsule to determine the origin and
      identity of the regions of a capsule that the hatching substance must remove. The
      results show that the Ilyanassa egg capsule is organized into four layers, the
      outer three of which are composed of protein and carbohydrate. Portions of the
      two inner layers of the capsule wall extend into the capsule apex and form the
      plug, which is dissolved by the hatching substance. The isolated capsule plug
      region contains three major glycoproteins resolved on sodium dodecyl sulfate
      polyacrylamide gels. Therefore, the hatching substance may be a protease similar
      in action to the enzymes released by many other embryos at hatching.

PMID- 29320254
TI  - SKELETAL STRENGTH OF ENCRUSTING CHEILOSTOME BRYOZOANS.
AB  - Encrusting cheilostome bryozoans structurally resemble aggregates of small boxes,
      with both frontal and vertical walls capable of resisting forces generated by
      water-borne debris or predators. Both the skeletal strength and design of the
      walls are important in determining the relative ability of the colony to resist
      damage. Two mechanical tests, puncture and compression, performed on nine species
      of tropical bryozoans reveal significant differences in skeletal strength both
      between species and between the outer and inner regions of colonies. Puncture
      stresses required to break through the frontal walls of zooids range from 0.8 to
      291.0 MNm-2 for edge zooids and from 1.1 to 457.4 MNm-2 for inner zooids;
      compressive stresses required to damage the colony range from 4.4 to 16.9 MNm-2
      for edge regions and 6.5 to 27.2 MNm-2 for inner regions. Ecological implications
      for these differences in skeletal strength are discussed with particular
      reference to resisting predation. From the mechanical test results, the material
      properties of shear strength (2.6-90.5 MNm-2) and compressive strength (8.2-110.0
      MNm-2) are estimated for the frontal and vertical walls, respectively. Bryozoan
      wall material appears to be comparable in strength to such biological ceramics as
      coral, echinoid spine, bivalve shell, and vertebrate bone, but lower in strength
      than gastropod shell.

PMID- 29320255
TI  - PHYSIOLOGICAL AND MORPHOLOGICAL STATE OF THE SYMBIOTIC BACTERIA FROM LIGHT ORGANS
      OF PONYFISH.
AB  - Symbiotic, bioluminescent bacteria (Photobacterium leiognathi) within and
      directly removed from the light organs of freshly sacrificed Philippine and
      Japanese ponyfish (family Leiognathidae) were analyzed for light production,
      oxygen uptake, morphology, and density. Luminescence averaged 2.4 x 104 quanta.s
      1 . cell-1 for bacteria from 24 fish (6 species in 3 genera), more than 10 times
      the maximum luminescences of P. leiognathi grown in culture. Light production
      (depending on the in vivo quantum yield for luminescence, 0.1 to 1.0) accounted
      for 1.7 to 17% of the total oxygen utilized by bacteria from the light organ,
      substantially more than found for P. leiognathi in culture. Bacteria from the
      light organ were non-motile, non-flagellated coccobacilloid to short rod-shaped
      cells (1.6 x 3.2 um), whereas in culture they showed motility and polar
      flagellation. In situ doubling time for the population of light organ bacteria
      was estimated to be approximately one day, or 20 to 30 times slower than in
      culture. Within the tubules of the light organ, the bacteria were solidly packed
      inside elongate, thinly-walled saccules, with one to 20 saccules tightly filling
      each light organ tubule. The saccules held the bacteria at a density (calculated
      from bacterial cell and saccule volumes) of approximately 1 x 1011 cells.ml-1,
      which is a density roughly 15 times greater than estimated from total light organ
      volume. These findings lead to a maximalluminescence, minimal-growth bacterial
      model of this symbiosis.

PMID- 29320256
TI  - Yet Another Glucose Variability Index: Time for a Paradigm Change?

PMID- 29320257
TI  - ENVIRONMENTAL CONTROL OF AMYLASE PHENOTYPE IN AMPHIPODS OF THE GENUS GAMMARUS.
AB  - The amylases of three species of Gammarus amphipods, G. palustris, G. mucronatus,
      and G. lawrencianus, were studied using polyacrylamide gel electrophoresis. In
      all three species there are two principal zones of activity (Amy-1 and Amy-2),
      but occasional individuals exhibit a third band(Amy-X). Amy-X variants are more
      common in the deeper water species and in collections made during late winter or
      early spring than in the shallower water species or in summer collections.
      Experimental work shows that Amy-X can be induced by a diet rich in amylose or
      glycogen, but not by amylopectin or other foods, and by reducing the temperature
      at which they are maintained. It is hypothesized that the relative expressions of
      Amy-X and Amy-1 vary seasonally, and that this variation is an adaptive response
      to seasonal variation in diet, or conditions for the hydrolysis of substrate.

PMID- 29320258
TI  - CHROMOSOME POLYMORPHISM IN GOBIUS PAGANELLUS, LINNEO 1758 (PISCES, GOBIIDAE).
AB  - In the present investigation the diploid numbers 2n = 45, 2n = 46, 2n = 47, and
      2n = 48 have been determined for Gobius paganellus. Specimens of different sex
      were found to have exactly the same karyotype. This species is characterized by
      two fundamental numbers: NF = 47, and NF = 48. Chromosome polymorphism due to
      different chromosome rearrangements within the A-type complement is present in
      this species.

PMID- 29320259
TI  - NUTRIENT TRANSLOCATION IN THE SEA STAR: WHOLE-BODY AND MICROAUTORADIOGRAPHY AFTER
      INGESTION OF RADIOLABELED LEUCINE AND PALMITIC ACID.
AB  - Using the sea star, Asterias rubens, whole-body autoradiography has been employed
      to follow the distribution and the pathways of translocation of both soluble and
      tissue-incorporated label derived from orally administered 14C-labeled leucine or
      palmitic acid. Radioactivity remains localized predominantly in the stomach and
      pyloric caeca until sixteen days after ingestion. Labeling of the perivisceral
      coelomic cavity in regions close to the stomach shortly after ingestion points to
      initial displacement of ingested nutrients through the coelomic fluid and
      coelomocytes. After oral administration of labeled palmitic acid, distinct
      labeling of the gastric hemal tufts, axial organ, and aboral ring prior to
      labeling of the gonads also suggests the involvement of hemal tissue and
      surrounding perihemal coelomic sinuses in storage and translocation of substances
      needed for gamete nutrition. Microautoradiography of gonad tissue reveals a rapid
      labeling of the walls of the genital coelomic sinus, the ground substance of the
      genital hemal sinus, and, after prolonged incubation, the germinal epithelium.
      Little or no label is incorporated into the outer sac of the gonad wall. The
      results are discussed in terms of current knowledge on nutrient translocation in
      the sea star.

PMID- 29320260
TI  - COPULATION BY HYPODERMIC INJECTION IN THE NUDIBRANCHS PALIO ZOSTERAE AND P. DUBIA
      (GASTROPODA, OPISTHOBRANCHIA).
AB  - The Pacific nudibranch Palio (= Polycera) zosterae and the Atlantic P. dubia
      copulate in a manner different from that of most nudibranchs. Nudibranchs are
      hermaphroditic and normally copulate reciprocally, with the intromittant organ of
      one inserted in the vaginal opening of the other. P. zosterae and P. dubia lack a
      complete vaginal duct. Copulation is usually reciprocal but involves the piercing
      of the body wall by a barbed, eversible penial cirrus. If the cirrus injects
      exogenous sperm into the body wall or the haemocoel, the sperm are phagocytosed
      by blood cells. If the cirrus penetrates the gonad, exogenous sperm may be
      injected into a spermatogenic acinus. After traveling down the hermaphroditic
      duct to the anterior reproductive organs, these sperm presumably are sorted from
      endogenous sperm and stored in the receptaculum seminis. The organization of the
      reproductive system in Palio differs markedly from that in members of the closely
      related genus Polycera.

PMID- 29320261
TI  - PHOTOBIOLOGY OF THE SYMBIOTIC SEA ANEMONE, ANTHOPLEURA ELEGANTISSIMA: DEFENSES
      AGAINST PHOTODYNAMIC EFFECTS, AND SEASONAL PHOTOACCLIMATIZATION.
AB  - The sea anemone Anthopleura elegantissima, which contains photosynthetic
      symbionts (zooxanthellae), responds both biochemically and behaviorally to the
      combined environmental stresses of exposure to sunlight and photosynthetically
      generated hyperbaric O2. Activities of the enzymes superoxide dismutase (SOD) and
      catalase, which act in concert as defenses against oxygen toxicity, parallel the
      distribution of chlorophyll. A. elegantissima shows a finely controlled
      contraction behavior which shades the zooxanthellae and reduces O2 production,
      but which leaves the body column tissues directly exposed to sunlight. However,
      the body column contains disproportionately high SOD and catalase activities as
      defenses against photodynamic damage. This additional role of SOD is demonstrated
      by shade-adapted aposymbiotic anemones in which SOD and catalase activities
      increase by 590% and 100% respectively following a 7 day exposure to sunlight. In
      response to elevated levels of O2 and sunlight exposure, A. elegantissima
      attaches gravel and other debris to its body surface which serves as a sunscreen
      that effectively reduces zooxanthella expulsion during exposure to bright
      sunlight. Finally, anemone chlorophyll content fluctuates on a seasonal basis,
      varying inversely with mean solar radiation. These seasonal changes are not due
      to corresponding changes in the number of algal cells, but rather to changes in
      the chlorophyll content and chlorophyll a:c2 ratio of a fairly uniform standing
      crop of zooxanthellae.

PMID- 29320262
TI  - CRITICAL WEIGHTS FOR METAMORPHOSIS IN THE TOBACCO HORNWORM, MANDUCA SEXTA.
AB  - Fifth-instar larvae of the tobacco hornworm underwent a supernumerary larval molt
      under several feeding regimens. Supernumerary molting occurred only when the molt
      was initiated at a live weight less than about 3 g; at higher weights pupation
      took place. The supernumerary sixth instars were normal in appearance and
      behavior and went on to form normal pupae only when the fifth instar had begun at
      weights less than 1 g. Otherwise the supernumerary sixth instars exhibited
      precocious metamorphosis of their crochets and imaginal discs and failed to
      undergo normal pupation. Thus, the commitment to pupal development appears to
      occur in stages. A first stage, initiated at a weight of about 1 g, commits the
      crochets and imaginal discs to metamorphosis at the next molt. A second stage,
      entered at a weight of about 3 g, permits the full and complete pupation of the
      remaining tissues; this transition probably reflects the elimination of juvenile
      hormone (JH). Starvation apparently alters the normal patterns of ecdysone
      production, breakdown, or sensitivity so as to elicit ecdysone-dependent
      development at lower than normal weights. When starvation results in fifth-instar
      larvae initiating a developmental response at weights below 3 g, a supernumerary
      larval molt occurs. But in this case the critical effect of starvation is on the
      timing of the molt rather than on the JH titer, since the latter even in normally
      fed early fifth instars is high at weights below 3 g.

PMID- 29320263
TI  - DIGESTION AND DISTRIBUTION OF TRIPALMITOYLGLYCEROL IN DIPLODON DELODONTUS
      (MOLLUSCA, BIVALVIA).
AB  - Fat digestion, absorption, and transport in the fresh water mollusc Diplodon
      delodontus were studied after 1 and 6 h of force-feeding 14C tripalmitoylglycerol
      and 1-14C palmitic acid. In a 1 h period, the mollusc was able to hydrolyze more
      than 50% of the triacylglycerol to free acids monoacyl and diacylglycerols.
      Digestion and absorption was completed before the 6 h feeding, and most of the
      label was eliminated. Hydrolysis occurred primarily in the stomach. The mollusc
      absorbed the products of hydrolysis and apparently triacylglycerol molecules,
      too. During the period of tripalmitoylglycerol digestion (1 h), the labeled
      palmitic acid was transported by the hemolymph in the free acid,
      monoacylglycerol, and triacylglycerol fractions that were also the principal
      components found in the stomach. During the post absorption period (6 h) the
      label was principally bound to triacylglycerols. When 1-14C palmitic acid was fed
      to D. delodontus, the acid was absorbed and the label transported exclusively in
      the free acid fraction of the hemolymph during the first hour. At 6 h ~75% was
      still transported as free acid and the rest as triacylglycerol. The free palmitic
      acid was incorporated in the soft tissues of the mollusc and slowly esterified to
      triacylglycerols.

PMID- 29320264
TI  - DETERMINANTS OF LARVAL MOLT INITIATION IN THE TOBACCO HORNWORM, MANDUCA SEXTA.
AB  - Hornworm larvae adhere to Dyar's rule under normal growth conditions, increasing
      their live weight by an average of 5- to 6-fold from the outset of one instar to
      the next. This adherence to Dyar's rule is largely maintained even in instars
      subsequent to those in which larvae have been severely malnourished. The
      importance of relative weight gain for the normal onset of larval molting
      contrasts with the requirement for attainment of an absolute body weight prior to
      pupation. But body size is by no means the sole cue for the initiation of a
      larval molt. Thus, under conditions of malnutrition larvae can initiate a molt at
      any weight and can do so even in the absence of any weight gain in an instar: in
      these circumstances the duration of an instar is inversely related to the weight
      at the outset of malnutrition. In larvae fed ad lib as well as in malnourished
      larvae the initiation of a molt appears to be limited to a discrete phase of the
      photocycle. The failure of larvae to molt on schedule at body weights lower than
      those predicted by Dyar's rule cannot be attributed to an inability of the brain
      to stimulate ecdysone-dependent development as is the case in diapausing pupae.
      Though body size, instar duration, and photocycle all interact to determine the
      onset of the molt, the role of the brain remains ill-defined.

PMID- 29320265
TI  - RELATIONSHIPS BETWEEN FREE CUPRIC ION CONCENTRATIONS IN SEA WATER AND COPPER
      METABOLISM AND GROWTH IN CRAB LARVAE.
AB  - Crab larvae (Rhithropanopeus harrisiiere exposed to a range of free cupric ion
      concentrations, [Cu2+], regulated in sea water by a metal chelate buffer system.
      We found a biphasic relationship between intracellular copper distribution and
      [Cu2+] in sea water. At [Cu2+] within the ambient range (10-12.4 to 10-10.6 M),
      cytosolic copper was associated with both metallothionein (MT) and high molecular
      weight (HMW) ligands, and was independent of external [Cu2+]. At higher [Cu2+],
      copper was also associated with very low molecular weight (VLMW) ligands, and
      accumulated in this ligand pool and the MT pool as external [Cu2+] increased. In
      marked contrast, copper in the HMW ligand pool did not correlate with [Cu2+] in
      sea water over the entire range of exposures. Reductions in larval growth
      occurred at greater than estimated ambient [Cu2+] and correlated with copper
      accumulation in the MT and VLMW pools.

PMID- 29320266
TI  - FOOD-INDUCED SIZE-SPECIFIC MOLT SYNCHRONY OF THE SAND CRAB, EMERITA ANALOGA
      (STIMPSON).
AB  - Synchronous molting was found in both laboratory and field populations of the
      intertidal, filter feeding anomuran Emerita analoga. Molt synchrony resulted in
      distinct peak and trough molting periods which were apparently independent of
      lunar phase and not pheromonally entrained. The intermolt period for Emerita was
      correlated with animal size. Laboratory experiments showed that the molt cycles
      of a previously synchronized group of female Emerita analoga could be
      desynchronized and resynchronized by altering feeding regimes. It is proposed
      that in nature the increase in phytoplankton, which characterizes the spring
      bloom, entrains the synchronous molting rhythm observed in the field. Synchrony
      tends to be obscured in field samples composed of broad size ranges because of
      the size-specific character of the intermolt period. For animals which molt
      synchronously, estimates of growth rate based on molt frequency data extrapolated
      from field samples can be variable and misleading.

PMID- 29320267
TI  - THE DIMORPHIC CLAWS OF THE HERMIT CRAB, PAGURUS POLLICARIS: PROPERTIES OF THE
      CLOSER MUSCLE.
AB  - The first pair of chelipeds of the flat clawed hermit crab (Pagurus pollicaris)
      are dimorphic. The crusher claw is always on the right side and is larger than
      the cutter claw on the left. The closer muscle in the crusher claw has a wet
      weight that is 3.4 times greater than that in the smaller cutter claw. The closer
      muscle fiber types are different in the two claws. The crusher closer muscle has
      fibers with long (9-14 um) sarcomeres, a high thin to thick filament ratio, and
      low myofibrillar ATPase activity; these fibers are presumably slow. The cutter
      closer, by contrast, has two types of fibers that are regionally distributed
      within the muscle. Fibers located on the dorsal and ventral margins of the muscle
      have long (8-13 um) sarcomeres, a high thin to thick filament ratio, low
      myofibrillar ATPase activity, and are presumably slow fibers. In the central
      portion of the cutter closer muscle, however, there is a band of fibers with
      short sarcomeres and high myofibrillar ATPase activity. These features suggest
      that these fibers are fast. However, the high thin to thick filament ratio found
      in these "fast" muscle fibers would argue against this presumption. Finally,
      sarcomere length measurements taken from closer muscle fibers in other thoracic
      appendages revealed a bimodal distribution of fiber types similar to that
      observed in the cutter claw.

PMID- 29320268
TI  - HOST FEEDING REGIME AND ZOOXANTHELLAL PHOTOSYNTHESIS IN THE ANEMONE, AIPTASIA
      PALLIDA (VERRILL).
AB  - Oxygen production was measured in the anemone Aiptasia pallida (Verrill)
      maintained at varying feeding regimes in the laboratory. Host feeding regime had
      no significant effect on: (1) zooxanthellal gross photosynthesis (GPPmax)
      expressed as ug O2 . ug chl a-1 . h-1 or ug O2 . 106 zooxanthellae-1 . h-1; (2)
      the light intensity at which 1/2 GPPmax occurs (Km); or (3) the chlorophyll a
      content of the zooxanthellae. Starvation significantly reduced GPPmax expressed
      as ug O2 . mg host protein-1 . h-1 and zooxanthellal density within the host.
      Zooxanthellal translocation efficiency was measured by short term incubations of
      anemones in NaH14CO3. Host feeding regime had no effect on the percentage of 14C
      translocated to the host. These results suggest that, under these conditions,
      starvation did not alter the photosynthetic capability of the zooxanthellae but
      decreased total photosynthate translocated to the host by decreasing
      zooxanthellal density within the host.

PMID- 29320269
TI  - PHOTOSYNTHETIC PRODUCTION BY THE CORAL REEF ANEMONE, LEBRUNIA CORALLIGENS WILSON,
      AND BEHAVIORAL CORRELATES OF TWO NUTRITIONAL STRATEGIES.
AB  - The coral reef anemone Lebrunia coralligens Wilson bears, in addition to its
      lanceolate, feeding tentacles, lobate pseudotentacles which are shown to be
      photosynthetic organs. Anemones exposed to light demonstrate a net oxygen
      production and, when incubated in NaH14CO3 in the light, incorporate 14C into the
      zooxanthellae and animal tissue. Diurnal rhythms of pseudotentacle expansion and
      contraction are under the control of ambient light but are modified by the
      animal's nutritional status. Unfed animals utilize their lobate pseudotentacles
      to obtain the maximum nutritional uptake by autotrophy while fed animals reduce
      their autotrophic intake. However, lanceolate tentacle expansion is primarily a
      feeding response and is augmented by a higher nutritional state. It is concluded
      that anemone behavior is an expression of the two nutritional strategies.

PMID- 29320270
TI  - PATTERNS OF WHOLE COLONY PREY CAPTURE IN THE OCTOCORAL, ALCYONIUM SIDERIUM.
AB  - Colonies of a boreal octocoral, Alcyonium siderium, preferentially catch prey on
      specific regions of the colony at certain flow speeds of low turbulence. Colonies
      feeding on brine shrimp cysts capture prey preferentially on the upstream side of
      the colony under low flow conditions (2.5 cm . s-1). At intermediate flow speeds
      (9.0 cm . s-1), prey capture is uniformly distributed around the circumference of
      the colonies, while at higher flow speeds (19.0 cm . s-l), prey capture again
      becomes asymmetric and downstream polyps capture the most prey. At higher levels
      of free-stream turbulence, these asymmetric prey capture distributions around the
      colony disappear; in the vertical direction, prey capture is asymmetric over the
      surface of the colony at all flow speeds tested, with polyps nearer the top of
      the colony capturing the most prey only at the lowest speeds. Asymmetrical
      filtration results from (1) increasing mechanical deformation of polyps into an
      orientation unfavorable for prey capture with increasing flow speed, and (2)
      differential prey concentrations in the boundary layer of the colony in the
      downstream direction. For non-motile particles, the filtration performance of
      this passive suspension feeder appears governed only by the flow speed and
      turbulence, the mechanical behavior of the filter elements, and the motion of the
      particles in the boundary layer of the colony.

PMID- 29320271
TI  - OBSERVATIONS ON THE LONG-TERM POPULATION DYNAMICS OF THE PERENNIAL ASCIDIAN,
      ASCIDIA MENTULA O. F. MULLER, ON THE SWEDISH WEST COAST.
AB  - Six populations of Ascidia mentula O. F. Muller on subtidal vertical rock walls
      were monitored continually for 12 years (1971-1982) using stereophotographic
      techniques. Three stations at two depth levels were observed, along a
      hydrographical gradient extending 100 km from the sheltered inner parts of the
      Gullmarsfjord to the exposed archipelago off the Swedish west coast. Population
      densities increased during 1971-1976, and gradually declined from 1976.
      Recruitment was density-dependent while mortality was density-independent.
      Temporal covariation in recruitment between stations and depths separated fjord
      stations into two independent, correlated patterns:(1) the exposed archipelago
      station and the shallow semi-sheltered fjord station from (2) the shallow
      sheltered fjord station from the sheltered and deep semi-sheltered fjord station.
      Temporal covariation in mortality separated the exposed station from the
      sheltered fjord stations suggesting different mortality factors. Histological
      analysis of gonads and analysis of photographically monitored recruitment
      revealed a seasonal reproductive pattern at 15 m depth while continuous
      reproduction and recruitment was observed in deeper populations. Temporal
      patterns of population density appeared to be related to long-term hydrographic
      changes mediated by variation in recruitment. Mortality caused by predation was
      not observed but disturbance and dislocation by sea urchins was an important
      mortality factor, especially at exposed sites.

PMID- 29320272
TI  - Ethical review in Avian Pathology.

PMID- 29320276
TI  - How Should the Epidemiology of Acute Hepatitis C and Opioid Use Affect Health
      Policy Decision-Making?

PMID- 29320277
TI  - Rothman et al. Respond.

PMID- 29320278
TI  - Prioritizing Posttrafficking Care for Trafficked Individuals.

PMID- 29320279
TI  - Impact of Tax Innovations on Families With Young Children.

PMID- 29320280
TI  - Opioids, Hepatitis C Virus Infection, and the Missing Vaccine.

PMID- 29320281
TI  - On Creating Positive Spillovers to Improve the Health of Populations: A Public
      Health of Consequence, February 2018.

PMID- 29320282
TI  - Public Health Issues in 2016 Presidential Campaign Communications.

PMID- 29320283
TI  - Prevention of Elevated Blood Lead Levels Among Child Refugees and Other
      Susceptible Populations.

PMID- 29320284
TI  - Cross-Sector Partnerships Will Shape the Future of Public Health.

PMID- 29320286
TI  - Tobacco Policies and Alcohol Sponsorship at Lesbian, Gay, Bisexual, and
      Transgender Pride Festivals: Time for Intervention.

PMID- 29320287
TI  - Leprosy: An Early Exemplar of the Transformation of 20th Century American
      Medicine.

PMID- 29320288
TI  - Policy Evaluation With Incomplete Data: Assessing the Affordable Care Act
      Breastfeeding Provision.

PMID- 29320289
TI  - Legal and Administrative Feasibility of a Federal Junk Food and Sugar-Sweetened
      Beverage Tax to Improve Diet.
AB  - OBJECTIVES: To evaluate legal and administrative feasibility of a federal "junk"
      food (including sugar-sweetened beverages [SSBs]) tax to improve diet. METHODS:
      To assess food definitions and administration models, we systematically searched
      (1) PubMed (through May 15, 2017) for articles defining foods subject to taxes,
      and legal and legislative databases as well as online for (2) US federal, state,
      and tribal junk food tax bills and laws (January 1, 2012-February 28, 2017); SSB
      taxes (January 1, 2014-February 28, 2017); and international junk food tax laws
      (as of February 28, 2017); and (3) federal taxing mechanisms and administrative
      methods (as of February 28, 2017). RESULTS: Articles recommend taxing foods by
      product category, broad nutrient criteria, specific nutrients or calories, or a
      combination. US junk food tax bills (n = 6) and laws (n = 3), international junk
      food laws (n = 2), and US SSB taxes (n = 10) support taxing foods using category
      based (n = 8), nutrient-based (n = 1), or combination (n = 12) approaches.
      Federal taxing mechanisms (particularly manufacturer excise taxes on alcohol) and
      administrative methods provide informative models. CONCLUSIONS: From legal and
      administrative perspectives, a federal junk food tax appears feasible based on
      product categories or combination category-plus-nutrient approaches, using a
      manufacturer excise tax, with additional support for sugar and graduated tax
      strategies.

PMID- 29320290
TI  - Time for a Top-Down Approach to Hearing Aid Affordability and Accessibility.

PMID- 29320291
TI  - Funding for Gun Violence Research Is Key to the Health and Safety of the Nation.

PMID- 29320292
TI  - Further Considerations for Research on Human Trafficking.

PMID- 29320293
TI  - The Challenges of Monitoring Illicit Trade Should Not Obscure the Success of
      Tobacco Tax Policy.

PMID- 29320294
TI  - Arresting Leprosy: Therapeutic Outcomes Besides Cure.
AB  - This essay focuses on the use of the concept of "arrest" in Hansen's disease
      (leprosy) in the United States in the early to middle part of the 20th century,
      as well as the transformations the concept underwent with the arrival of sulfone
      drugs and the implications of these changes for patients and public health
      officers. An "arrest" was a therapeutic outcome characterized by a long course of
      treatment, noncontagiousness, a very small chance of reactivation, and a need for
      postdischarge maintenance that depended on sociomedical infrastructures beyond
      the clinic as well as self-imposed lifestyle limitations. The concept of disease
      arrest shows that experts and laypeople alike have valued therapeutic outcomes
      other than "cure" that signal certain optimal therapeutic milestones, despite the
      practical difficulties they imply and despite the fact that they do not promise a
      return to a pre-illness stage.

PMID- 29320295
TI  - Rothman et al. Respond.

PMID- 29320297
TI  - Estimates Research on Human Trafficking.

PMID- 29320296
TI  - Is Forgiveness a Public Health Issue?

PMID- 29320299
TI  - Comprehensive Restaurant-Sector Changes Are Essential to Reduce Obesity Risk for
      All Americans.

PMID- 29320300
TI  - AJPH Global News.

PMID- 29320301
TI  - Using Cost-Related Medication Nonadherence to Assess Social and Health Policies.

PMID- 29320302
TI  - Federal Right-to-Try Legislation - Threatening the FDA's Public Health Mission.

PMID- 29320303
TI  - Time of day and short-duration high-intensity exercise influences on coagulation
      and fibrinolysis.
AB  - Exercise has been demonstrated to have considerable effects upon haemostasis,
      with activation dependent upon the duration and intensity of the exercise bout.
      In addition, markers of coagulation and fibrinolysis have been shown to possess
      circadian rhythms, peaking within the morning (0600-1200 h). Therefore, the time
      of day in which exercise is performed may influence the activation of the
      coagulation and fibrinolytic systems. This study aimed to examine coagulation and
      fibrinolytic responses to short-duration high-intensity exercise when completed
      at different times of the day. Fifteen male cyclists (VO2max: 60.3 +/- 8.1 ml kg
      1 min-1) completed a 4-km cycling time trial (TT) on five separate occasions at
      0830, 1130, 1430, 1730 and 2030. Venous blood samples were obtained pre- and
      immediately post-exercise, and analysed for tissue factor (TF), tissue factor
      pathway inhibitor (TFPI), thrombin-anti-thrombin complexes (TAT) and D-Dimer.
      Exercise significantly increased plasma concentrations of TF (p < .0005), TFPI (p
      < .0006), TAT complexes (p < .0012) and D-Dimer (p < .0003). There was a time-of
      day effect in pre-exercise TF (p = .004) and TFPI (p = .031), with 0830 greater
      than 1730 (p  .001), while 1730 was less than 2030 h (p = .008), respectively.
      There was no significant effect of time of day for TAT (p = .364) and D-Dimer (p
      = .228). Power output, TT time and heart rate were not significantly different
      between TTs (p > .05); however, percentage VO2max was greater at 1730 when
      compared to 2030 (p = .04). Due to a time-of-day effect present within TF,
      peaking at 0830, caution should be applied when prescribing short-duration high
      intensity exercise bout within the morning in populations predisposed to
      hypercoagulability.

PMID- 29320304
TI  - Complications of Sling Surgery for Stress Urinary Incontinence Among Female
      Military Beneficiaries.
AB  - BACKGROUND: Prior studies of complications after sling surgery excluded the large
      number of women in military treatment facilities (MTFs). OBJECTIVE: To
      characterize the postoperative complication rates after sling surgery for Stress
      urinary incontinence (SUI) within MTFs in the United States. MATERIALS AND
      METHODS: Retrospective cohort study of women aged 18 and older, with SUI, and who
      underwent either an outpatient or inpatient mid-urethral sling placement for SUI
      in any MTF in the United States between January 1, 2011 and December 31, 2012.
      RESULTS: During the study period, 348 surgeons performed 1632 slings. The average
      patient age was 47.2 years, and 22.4% of the patients had a concomitant pelvic
      organ prolapse procedure. Overall, 45.5% of subjects had at least one
      postoperative complication. Of the specific complications, urologic infectious
      complications were the most frequent, occurring in 25.2% of patients. Overall,
      only 0.9% of patients underwent a repeat incontinence procedure. In multivariate
      analyses, concomitant pelvic organ procedure was associated with an increased
      risk of bladder outlet obstruction and noninfectious urologic complications.
      Those with a Charlson comorbidity index score of 1 or more were more likely to
      have an infectious complication and a new diagnosis of pelvic pain. Women older
      than the median age were less likely than those below to experience treatment
      failure and a new diagnosis of pelvic pain. CONCLUSIONS: The population of women
      with SUI undergoing sling surgery at MTFs is a young population with
      postoperative complication rates lower than previously reported. However, the
      absolute overall complication rate is still high, specifically related to urinary
      tract infections, suggesting that significant opportunities exist for quality
      improvement.

PMID- 29320305
TI  - Social physique anxiety and physical activity behaviour of male and female
      exercisers.
AB  - Despite females consistently reporting greater social physique anxiety (SPA),
      previous literature has yet to demonstrate whether SPA gender differences are
      linked to the way males and females perform physical activity. This study
      investigated an association between SPA and physical activity frequency, history
      of exercise, and physical activity intensity. Participants were represented by
      currently active users (N = 33 males; N = 31 females) of an on-campus university
      run gym and completed a background physical activity questionnaire and the nine
      item Social Physique Anxiety Scale. Participants also performed an exercise
      session at a self-selected level of exertion, with the intensity of each session
      measured via heart rate monitor. SPA was not associated with physical activity
      frequency, history of exercise (length of gym membership), or intensity for male
      and female exercisers. With respect to male participants, females reported higher
      SPA and a preference for performing higher intensity physical activity. Females
      and males also indicated a preference for performing aerobic and anaerobic
      physical activity respectively. Our findings suggest the experience of SPA does
      not deter body-conscious individuals from the performance of regular physical
      activity. Findings also suggest the discrepancy in male and female SPA is not
      linked to differences in the way physical activity is performed.

PMID- 29320306
TI  - Disease staging and sub setting of interstitial lung disease associated with
      systemic sclerosis: impact on therapy.
AB  - INTRODUCTION: Interstitial lung disease (ILD) is the most serious complication of
      systemic sclerosis (SSc). There is no accepted guidance as to which clinical,
      radiological or physiological thresholds should prompt initiation or changes in
      treatment. Furthermore, some patients with extensive disease remain stable
      without the need for intervention whilst others with limited disease at the
      outset, experience a precipitous decline. Areas covered: In this article,
      evidence for the integration of a number of disease-specific and patient-related
      domains are discussed and proposed. Introduction and maintenance of therapy
      requires a nuanced understanding of these factors and is crucial when weighing up
      the risks and benefits of immunomodulation. The evidence for the existing
      treatment modalities is discussed and the future directions for management of
      patients with SSc-ILD, which may include antifibrotic or biologic therapy, are
      explored. Expert commentary: In the management of SSc-ILD, a multidisciplinary
      team approach which integrates physiology and radiology with the patient at the
      centre of the process is crucial for effective management and provision of the
      best outcomes.

PMID- 29320307
TI  - Musculoskeletal injuries in professional modern dancers: a prospective cohort
      study of 15 years.
AB  - We analysed work-related musculoskeletal injuries (WMSI) in two modern dance
      companies to determine whether injury rates decreased and patterns altered
      compared to previous 3-yr and 6-yr audits (0.48 and 0.25/1000-hrs exposure
      respectively). In this prospectively designed 15-yr cohort study, data were
      collected in 30-dancer Company-1 and 12-dancer Company-2. In-house physical
      therapists tracked WMSI and time-loss-injuries for 159 dancers (42 dancers/yr).
      15-yrs were grouped into five 3-yr blocks for comparison with prior audits.
      Negative binomial logistic regression analyses were conducted with exposure-hrs
      converted to the natural log and used as the offset variable. Block and company
      were categorical predictors for dependent variables: WMSI, time-loss-injuries,
      trauma-injuries and overuse-injuries (p < 0.05). 69% of dancers reported WMSI;
      45% sustained at least one time-loss-injury. Company-1, with greater annual
      exposure, was 1.6-times more likely to sustain time-loss-injuries (p = 0.016, CI
      = 1.095-2.422) and 5.6-times more likely to sustain time-loss overuse-injuries (p
      = 0.003, CI = 1.812-17.327). Compared to Block-1, WMSI and time-loss-injuries
      decreased in Blocks-2, 3, and 5 (p <= 0.027). The ratio of time-loss overuse to
      trauma-injuries was reversed, with trauma-injuries accounting for over 80% of
      injuries by Block 5. Time-loss-injuries averaged 0.16 injuries/1000-hrs, lower
      than rates in ballet and sports. Decreased injury rates and changed injury
      patterns demonstrate efficacious injury management and prevention programming.

PMID- 29320308
TI  - When the CHIPs Are Down - Health Coverage and Care at Risk for U.S. Children.

PMID- 29320309
TI  - Isocapnic buffering phase: a useful indicator of exercise endurance in patients
      with coronary artery disease.
AB  - OBJECTIVES: The significance of the isocapnic buffering (IB) phase - the period
      between the first ventilatory threshold (1st VT) and respiratory compensation
      point (RCP) - has not been adequately established in patients. This study aimed
      to determine the clinical significance of the IB phase in patients with coronary
      artery disease (CAD). METHODS: This retrospective study included data of sixty
      two CAD patients after coronary artery bypass graft (CABG) or percutaneous
      coronary intervention (PCI) performed in a single medical center between 2010 -
      2014. According to their physical conditions, the patients performed incremental
      cardiopulmonary exercise test (CPET) using a cycle ergometer by the ramp of 5-20
      W/min. Correlations between the corrected IB phase duration and age, body mass
      index (BMI), left ventricular ejection fraction (LVEF), and CPET parameters were
      evaluated using Pearson correlation coefficients. Variables predicting peak
      oxygen consumption (VO2) were evaluated using multiple regression. RESULTS: Peak
      VO2 (p < 0.001), VO2 at RCP (p < 0.001), ?O2/?WR slope (p < 0.001), maximal
      partial pressure of end tidal CO2 (PetCO2) (p = 0.0012), VE/VCO2 slope (p =
      0.010), BMI (p = 0.012), and age (p = 0.017) were significantly correlated,
      whereas LVEF (p = 0.246) and VO2 at 1st VT (p = 0.179) were not significantly
      correlated with the corrected IB phase duration. In multiple regression analysis,
      the corrected IB phase duration, VO2 at 1st VT, and ?O2/?WR slope were
      significantly associated with peak VO2. CONCLUSION: The findings indicate that
      the IB phase duration is a useful indicator of peripheral cardiopulmonary
      function and endurance performance in CAD patients. These findings could assist
      the exercise prescription of cardiac rehabilitation for patients with CAD.

PMID- 29320310
TI  - Comparison of current recruitment process for specialty or residency training in
      UK and USA.

PMID- 29320311
TI  - Development and Validation of a Risk Prediction Model for Acute Kidney Injury
      After the First Course of Cisplatin.
AB  - Purpose Cisplatin-associated acute kidney injury (C-AKI) is common. We sought to
      develop and validate a predictive model for C-AKI after the first course of
      cisplatin. Methods Clinical and demographic data were collected on patients who
      received cisplatin between 2000 and 2016 at two cancer centers. C-AKI was defined
      as a 0.3 mg/dL rise in serum creatinine within 14 days of receiving cisplatin.
      Using multivariable logistic regression models with C-AKI as the primary outcome,
      we created a scoring model from the development cohort (DC) and tested it in the
      validation cohort (VC). Results C-AKI occurred in 13.6% of 2,118 patients in the
      DC and in 11.6% of 2,363 patients in the VC. Factors significantly associated
      with C-AKI included age 61 to 70 years (odds ratio [OR], 1.64 [95% CI, 1.21 to
      2.23]; P = .001) and 71 to 90 years (OR, 2.97 [95% CI, 2.06 to 4.28]; P < .001)
      compared with <= 60 years; cisplatin dose 101 to 150 mg (OR, 1.58 [95% CI, 1.14
      to 2.19]; P = .007) and > 150 mg (OR, 3.73 [95% CI, 2.68 to 5.20]; P < .001)
      compared with <= 100 mg; a history of hypertension (OR, 2.10 [95% CI, 1.54 to
      2.72]; P < .001) compared with no hypertension; and serum albumin 2.0 to 3.5 g/dL
      (OR, 2.21 [95% CI, 1.62 to 3.03]; P < .001) compared with > 3.5 g/dL. The
      baseline estimated glomerular filtration rate was not significantly associated
      with the risk of C-AKI. The c-statistics of the score-based model in the DC and
      the VC were 0.72 (95% CI, 0.69 to 0.75) and 0.70 (95% CI, 0.67 to 0.73),
      respectively. Scores of 0, 3.5, and 8.5 were associated with a probability of C
      AKI of 0.03 (95% CI, 0.03 to 0.05), 0.12 (95% CI, 0.11 to 0.14), and 0.51 (95%
      CI, 0.43 to 0.60), respectively. Conclusion A score-based model created by using
      the patient's age, cisplatin dose, hypertension, and serum albumin is predictive
      of C-AKI.

PMID- 29320312
TI  - Targeted Therapy for Advanced Solid Tumors on the Basis of Molecular Profiles:
      Results From MyPathway, an Open-Label, Phase IIa Multiple Basket Study.
AB  - Purpose Detection of specific molecular alterations in tumors guides the
      selection of effective targeted treatment of patients with several types of
      cancer. These molecular alterations may occur in other tumor types for which the
      efficacy of targeted therapy remains unclear. The MyPathway study evaluates the
      efficacy and safety of selected targeted therapies in tumor types that harbor
      relevant genetic alterations but are outside of current labeling for these
      treatments. Methods MyPathway ( ClinicalTrials.gov identifier: NCT02091141) is a
      multicenter, nonrandomized, phase IIa multiple basket study. Patients with
      advanced refractory solid tumors harboring molecular alterations in human
      epidermal growth factor receptor-2, epidermal growth factor receptor, v-raf
      murine sarcoma viral oncogene homolog B1, or the Hedgehog pathway are treated
      with pertuzumab plus trastuzumab, erlotinib, vemurafenib, or vismodegib,
      respectively. The primary end point is investigator-assessed objective response
      rate within each tumor-pathway cohort. Results Between April 1, 2014 and November
      1, 2016, 251 patients with 35 different tumor types received study treatment. The
      efficacy population contains 230 treated patients who were evaluated for response
      or discontinued treatment before evaluation. Fifty-two patients (23%) with 14
      different tumor types had objective responses (complete, n = 4; partial, n = 48).
      Tumor-pathway cohorts with notable objective response rates included human
      epidermal growth factor receptor-2-amplified/overexpressing colorectal (38% [14
      of 37]; 95% CI, 23% to 55%) and v-raf murine sarcoma viral oncogene homolog B1
      V600-mutated non-small-cell lung cancer (43% [six of 14]; 95% CI, 18% to 71%).
      Conclusion The four currently approved targeted therapy regimens in the MyPathway
      study produced meaningful responses when administered without chemotherapy in
      several refractory solid tumor types not currently labeled for these agents.

PMID- 29320313
TI  - Acute Radiologic Manifestations of America's Opioid Epidemic.
AB  - The United States is in the midst of an opioid use epidemic, which has severe
      medical, social, and economic consequences. Addictions to and abuse of
      prescription and illicit opioids are increasing, and emergency department
      radiologists are increasingly being faced with the task of examining patients who
      present with opioid-related complications. These complications may be the result
      of direct drug toxicity or nonsterile injection of the drugs. Neurologic,
      musculoskeletal, cardiopulmonary, genitourinary, and gastrointestinal
      complications may be evident at diagnostic imaging in emergent settings. Heroin
      induced leukoencephalopathy, cerebral septic emboli, mycotic arterial aneurysms,
      soft-tissue infections, and infective endocarditis are some of the conditions
      that patients may be found to have after they present to the emergency
      department. In this article, the above topics, including clinical features,
      pathophysiology, imaging findings, and treatment options, are reviewed.
      Recognizing the limitations of diagnostic imaging modalities that are available
      to radiologists is equally important, as some conditions can be successfully
      diagnosed after the initial triage-for example, transesophageal echocardiography
      can be performed to diagnose infective endocarditis. The emergency department
      radiologist may be responsible for identifying acute conditions, which can be
      life threatening. Some of the more common emergent opioid-related conditions and
      complications are reviewed, with specific emphasis on cases in which emergency
      department radiologists encounter conditions for which additional expertise is
      required. Becoming familiar with the conditions directly related to the current
      opioid epidemic will enable the diagnosis of these entities in a timely and
      accurate manner. (c)RSNA, 2018.

PMID- 29320314
TI  - Focus on Readers' Needs in 2017 and Expanded Journal Features for 2018: Editor's
      Page.

PMID- 29320315
TI  - Contrast Enema Examination: Technique and Essential Findings: RadioGraphics
      Fundamentals | Online Presentation.

PMID- 29320316
TI  - Translabial US and Dynamic MR Imaging of the Pelvic Floor: Normal Anatomy and
      Dysfunction.
AB  - Pelvic floor dysfunction (PFD) is a common condition that typically affects women
      older than 50 years and decreases the quality of life. Weakening of support
      structures can involve all three pelvic compartments and cause a combination of
      symptoms, including constipation, urinary and fecal incontinence, obstructed
      defecation, pelvic pain, perineal bulging, and sexual dysfunction. The causes of
      PFD are complex and multifactorial; however, vaginal delivery is considered a
      major predisposing factor. Physical examination alone is limited in the
      evaluation of PFD; it frequently leads to an underestimation of the involved
      compartments. Imaging has an important role in the clinical evaluation, yielding
      invaluable information for patient counseling and surgical planning. Three- and
      four-dimensional translabial ultrasonography (US) is a relatively new imaging
      modality with high accuracy in the evaluation of PFD such as urinary
      incontinence, pelvic organ prolapse, and puborectalis avulsion. Evaluation of
      mesh implants is another important indication for this modality. Dynamic magnetic
      resonance (MR) imaging of the pelvic floor is a well-established modality for
      pelvic floor evaluation, with high-resolution images yielding detailed anatomic
      information and dynamic sequences yielding functional data. Specific protocols
      and dedicated image interpretation are required with both of these imaging
      methods. In this article, the authors review the normal anatomy of the female
      pelvic floor by using a practical approach, discuss the roles of translabial US
      and MR imaging in the investigation of PFD, describe the most appropriate imaging
      protocols, and illustrate the most common imaging findings of PFD in the
      anterior, middle, and posterior compartments of the pelvis. Online supplemental
      material is available for this article. (c)RSNA, 2018.

PMID- 29320318
TI  - Invited Commentary on "Mediastinal and Pleural MR Imaging: Practical Approach for
      Daily Practice".

PMID- 29320319
TI  - Coronary Artery Aneurysm Formation: Kawasaki Disease versus Atherosclerosis.

PMID- 29320320
TI  - MR Imaging and Cochlear Implants with Retained Internal Magnets: Reducing
      Artifacts near Highly Inhomogeneous Magnetic Fields.
AB  - The number of patients receiving cochlear implants and auditory brainstem
      implants for severe to profound sensorineural hearing loss has rapidly increased.
      These implants consist of an internal component implanted between the skull and
      the temporal scalp and an external removable speech processor unit. A small
      magnet within the internal component is commonly used to hold the external speech
      processor unit in place. Several cochlear implant models have recently received
      U.S. Food and Drug Administration and European Economic Area regulatory approval
      to allow magnetic resonance (MR) imaging examinations to be performed under
      certain specified conditions. The small internal magnet presents a challenge for
      imaging of the head and neck near the implant, creating a nonlinear magnetic
      field inhomogeneity and significant MR imaging artifacts. Fat-saturation failures
      and susceptibility artifacts severely degrade image quality. Typical artifacts at
      diffusion-weighted imaging and accelerated imaging are exacerbated. Each
      examination may require impromptu adjustments to allow visualization of the
      tissue or contrast of interest. Patients may also be quite uncomfortable during
      the examination, as a result of either imposed magnetic forces or a tight head
      wrap that is often applied to minimize internal magnet movement. Translational
      forces and torque sometimes displace the implanted magnet even when a head wrap
      is used. Diseases such as neurofibromatosis type 2 that are associated with
      bilateral vestibular schwannomas and hearing loss often require lifelong tumor
      surveillance with MR imaging. A collaborative team of radiologists,
      technologists, and/or medical physicists or MR imaging scientists, armed with
      strategies to mitigate artifacts near implanted magnets, can customize the
      examination for better visualization of tissue and consistent comparison
      examinations over time. (c)RSNA, 2018.

PMID- 29320321
TI  - Writing Good True-False Questions: A Brief Guide for Radiologists.
AB  - This guide provides a brief how-to compilation of widely accepted recommendations
      for creating good true-false questions for self-assessment continuing medical
      education exercises.

PMID- 29320322
TI  - Multidetector CT of Midfacial Fractures: Classification Systems, Principles of
      Reduction, and Common Complications.
AB  - The advent of titanium hardware, which provides firm three-dimensional positional
      control, and the exquisite bone detail afforded by multidetector computed
      tomography (CT) have spurred the evolution of subunit-specific midfacial fracture
      management principles. The structural, diagnostic, and therapeutic complexity of
      the individual midfacial subunits, including the nose, the naso-orbito-ethmoidal
      region, the internal orbits, the zygomaticomaxillary complex, and the maxillary
      occlusion-bearing segment, are not adequately reflected in the Le Fort
      classification system, which provides only a general framework and has become
      less relevant in contemporary practice. The purpose of this article is to
      facilitate the involvement of radiologists in the delivery of individualized
      multidisciplinary care to adults who have sustained blunt trauma and have
      midfacial fractures by providing a clinically relevant review of the role of
      multidetector CT in the management of each midfacial subunit. Surgically relevant
      anatomic structures, search patterns, critical CT findings and their management
      implications, contemporary classification systems, and common posttraumatic and
      postoperative complications are emphasized. (c)RSNA, 2018.

PMID- 29320323
TI  - Multimodality Imaging, including Dual-Energy CT, in the Evaluation of Gallbladder
      Disease.
AB  - Imaging of the gallbladder has a key role in the examination of patients with
      abdominal pain-especially pain localized to the right upper quadrant. Pathologic
      conditions that affect the gallbladder include cholelithiasis and associated
      complications such as acute and chronic cholecystitis, choledocholithiasis,
      gallstone pancreatitis, and cancer. Modalities used to image the gallbladder
      include ultrasonography (US), computed tomography (CT), magnetic resonance (MR)
      imaging, and nuclear scintigraphy. US is the primary imaging modality used to
      evaluate entities suspected of being gallbladder disease, as it is both sensitive
      and specific for demonstrating gallstones, biliary duct dilatation, and
      inflammatory features. However, CT is often the first imaging examination
      performed in patients who present to the emergency department with acute
      abdominal pain. Because the CT appearance of gallstones is variable, depending on
      the composition of the stone, pattern of calcification, and presence of gas,
      gallstones and other gallbladder conditions can be difficult to detect at
      conventional multidetector CT, with which data are acquired by using a single x
      ray energy spectrum. Dual-energy CT, with which one takes advantage of the
      material-dependent x-ray absorption behavior of concurrently acquired high- and
      low-kilovolt-peak data, can add value by increasing the conspicuity of
      noncalcified gallstones and improving the detection of acute cholecystitis and
      gallbladder malignancy. In addition, MR cholangiopancreatography can be helpful
      for assessing choledocholithiasis and complicated biliary duct disease. (c)RSNA,
      2018.

PMID- 29320324
TI  - Spectrum of Coronary Artery Aneurysms: From the Radiologic Pathology Archives.
AB  - Advances in medical diagnosis reveal that coronary artery aneurysms (CAAs) may
      develop in several clinical scenarios and manifest variable symptoms, imaging
      appearances, and outcomes. Aneurysms are pathologically classified into three
      groups: atherosclerotic, inflammatory, and noninflammatory. The last category is
      associated with congenital, inherited, and connective tissue disorders. Overlap
      exists among the groups, because secondary atherosclerotic change may be present
      in an aneurysm of any cause. Atherosclerosis is the most common cause of CAAs in
      adults, and inflammation is considered the underlying mechanism. In children,
      Kawasaki disease is the most likely cause of CAAs. In both conditions, the
      aneurysms are usually multiple and affect more than one coronary artery. Mycotic
      (infectious), iatrogenic, and cocaine-induced CAAs are also well documented. Most
      CAAs are discovered incidentally, but potential cardiovascular complications
      include thrombosis, occlusion, fistula formation, rupture, myocardial infarction,
      and cardiac tamponade. Imaging modalities to evaluate a suspected CAA include
      transthoracic echocardiography, angiographic cardiac catheterization,
      electrocardiographically gated computed tomographic angiography, cardiac magnetic
      resonance (MR) imaging, and MR angiography. Management is usually individualized,
      and options include surveillance, anticoagulant therapy, percutaneous stent or
      coil placement, surgical resection, and coronary artery bypass grafting.

PMID- 29320325
TI  - Diseases Involving the Central Bronchi: Multidetector CT for Detection,
      Characterization, and Differential Diagnosis.

PMID- 29320326
TI  - Mediastinal and Pleural MR Imaging: Practical Approach for Daily Practice.
AB  - Radiologists in any practice setting should be prepared to use thoracic magnetic
      resonance (MR) imaging for noncardiac and nonangiographic applications. This
      begins with understanding the sequence building blocks that can be used to design
      effective thoracic MR imaging protocols. In most instances, the sequences used in
      thoracic MR imaging are adapted from protocols used elsewhere in the body. Some
      modifications, including the addition of electrocardiographic gating or
      respiratory triggering, may be necessary for certain applications. Once protocols
      are in place, recognition of clinical scenarios in which thoracic MR imaging can
      provide value beyond other imaging modalities is essential. MR imaging is
      particularly beneficial in evaluating for benign features in indeterminate
      lesions. In lesions that are suspected to be composed of fluid, including
      mediastinal cysts and lesions composed of dilated lymphatics, MR imaging can
      confirm the presence of fluid and absence of suspicious enhancement. It can also
      be used to evaluate for intravoxel lipid, a finding seen in benign residual
      thymic tissue and thymic hyperplasia. Because of its excellent contrast
      resolution and potential for subtraction images, MR imaging can interrogate local
      treatment sites for the development of recurrent tumor on a background of post
      treatment changes. In addition to characterization of lesions, thoracic MR
      imaging can be useful in surgical and treatment planning. By identifying nodular
      sites of enhancement or areas of diffusion restriction within cystic or necrotic
      lesions, MR imaging can be used to direct sites for biopsy. MR imaging can help
      evaluate for local tumor invasion with the application of "real-time" cine
      sequences to determine whether a lesion is adherent to an adjacent structure or
      surface. Finally, MR imaging is the modality of choice for imaging potential
      tumor thrombus. By understanding the role of MR imaging in these clinical
      scenarios, radiologists can increase the use of thoracic MR imaging for the
      benefit of improved decision making in the care of patients. (c)RSNA, 2018.

PMID- 29320327
TI  - Atypical Sites of Deeply Infiltrative Endometriosis: Clinical Characteristics and
      Imaging Findings.
AB  - Endometriosis is defined as the presence of endometrial tissue that is located
      outside the uterine cavity and associated with fibrosis and inflammatory
      reaction. It is a polymorphic and multifocal disease with no known cure or
      preventive mechanisms. Patients may be asymptomatic or may experience chronic
      pelvic pain, dysmenorrhea, dyspareunia, or infertility. The pelvic cavity is the
      most common location for endometriotic implants, which usually affect the
      retrocervical space, ovaries, vagina, rectosigmoid colon, bladder dome, and round
      ligaments. Atypical endometriosis is rare and difficult to diagnose. The most
      common atypical locations are the gastrointestinal tract, urinary tract, lung,
      umbilicus, inguinal area, breast, and pelvic nerves, as well as abdominal
      surgical scars. Gastrointestinal lesions are the most common extragenital
      manifestation, and the diaphragm is the most frequent extrapelvic site. The
      catamenial nature of the symptoms (occurring between 24 hours before and 72 hours
      after the onset of menstruation) may help suggest the diagnosis, but imaging by
      specialists is fundamental to evaluation. Depending on the area affected,
      radiography, ultrasonography, thin-section computed tomography, or magnetic
      resonance imaging can be used to assess suspected lesions. Because isolated
      extragenital endometriosis is rare, concomitant evaluation of the pelvic cavity
      is mandatory. Surgical excision is the only therapeutic option for definitive
      treatment, and comprehensive disease mapping is necessary to avoid residual
      disease. The authors review atypical locations for endometriosis and emphasize
      the most appropriate imaging protocols for investigation of various clinical
      manifestations. Online supplemental material is available for this article.
      (c)RSNA, 2018.

PMID- 29320328
TI  - Twenty-Five Diagnoses on Midline Images of the Brain: From Fetus to Child to
      Adult.
AB  - Midsagittal images of the brain provide a wealth of anatomic information and may
      show abnormalities that are pathognomonic for particular diagnoses. Using an
      anatomy-based approach, the authors identify pertinent anatomic structures to
      serve as a checklist when evaluating these structures. Subregions evaluated
      include the corpus callosum, pituitary gland and sellar region, pineal gland and
      pineal region, brainstem, and cerebellum. The authors present 25 conditions with
      characteristic identifiable abnormalities at midsagittal imaging. Midsagittal
      views from multiple imaging modalities are shown, including computed tomography,
      ultrasonography, and magnetic resonance (MR) imaging. Standard MR imaging
      sequences are shown, as well as fetal MR and sagittal diffusion-weighted images.
      To demonstrate these conditions, fetal, neonatal, childhood, adolescent, and
      young adulthood images are reviewed. The differentiation of normal variants is
      guided by the understanding of anatomy and pathology. When a specific diagnosis
      is not possible, the authors present information to evaluate differential
      considerations and discuss when follow-up imaging may be indicated. The authors
      hope each case will clarify a pertinent differential diagnosis, appropriately
      guide patient management, and improve understanding of normal anatomy and
      identification of pathologic entities. It is in these hopes that the authors have
      presented a checklist of pertinent anatomy and pathologic entities that can build
      on existing search patterns. Improved confidence and accuracy in the evaluation
      of midsagittal images will benefit physicians and patients. (c)RSNA, 2018.

PMID- 29320329
TI  - CT Cystography for Suspicion of Traumatic Urinary Bladder Injury: Indications,
      Technique, Findings, and Pitfalls in Diagnosis: RadioGraphics Fundamentals |
      Online Presentation.

PMID- 29320330
TI  - Cardiovascular Manifestations and Complications of Loeys-Dietz Syndrome: CT and
      MR Imaging Findings.
AB  - Loeys-Dietz syndrome (LDS) is a recently described genetic connective tissue
      disorder with a wide spectrum of multisystem involvement. LDS is characterized by
      rapidly progressive aortic and peripheral arterial aneurysmal disease. LDS and
      the other inherited aortopathies such as Marfan syndrome have overlapping
      phenotypic features. However, LDS is characterized by a more aggressive vascular
      course; patient morbidity and mortality occur at an early age, with complications
      developing at relatively smaller aortic dimensions. In addition, there is more
      diffuse arterial involvement in LDS, with a large proportion of patients
      developing aneurysms of the iliac, mesenteric, and intracranial arteries. Early
      diagnosis and careful follow-up are essential for ensuring timely intervention in
      patients with arterial disease. Cross-sectional angiography has an important role
      in the baseline assessment, follow-up, and evaluation of acute complications of
      LDS, the thresholds and considerations of which differ from those of other
      inherited aortopathies. In this article, LDS is compared with other genetic
      vascular connective tissue disorders. In addition, the genetic, histopathologic,
      and cardiovascular manifestations of this disease process are reviewed, with a
      focus on computed tomographic and magnetic resonance imaging findings. Online
      DICOM image stacks and supplemental material are available for this article.
      (c)RSNA, 2018.

PMID- 29320331
TI  - Neuromyelitis Optica Spectrum Disorders: Spectrum of MR Imaging Findings and
      Their Differential Diagnosis.
AB  - Neuromyelitis optica (NMO) is an autoimmune demyelinating disorder for which the
      aquaporin-4 (AQP4) water channels are the major target antigens. Advances in the
      understanding of NMO have clarified several points of its pathogenesis, clinical
      manifestations, and imaging patterns. A major advance was the discovery of the
      AQP4 antibody, which is highly specific for this disorder. Descriptions of new
      clinical and radiologic features in seropositive patients have expanded the
      spectrum of NMO, and the term NMO spectrum disorder (NMOSD) has been adopted.
      NMOSD is now included in a widening list of differential diagnoses.
      Acknowledgment of NMOSD imaging patterns and their mimicry of disorders has been
      crucial in supporting early NMOSD diagnosis, especially for unusual clinical
      manifestations of this demyelinating disease. This pictorial review summarizes
      the wide imaging spectrum of NMOSD and its differential diagnosis, as well as its
      historical evolution, pathophysiology, and clinical manifestations. (c)RSNA,
      2018.

PMID- 29320332
TI  - Intraocular Medulloepithelioma: AIRP Best Cases in Radiologic-Pathologic
      Correlation.
AB  - Editor's Note.-RadioGraphics continues to publish radiologic-pathologic case
      material selected from the American Institute for Radiologic Pathology (AIRP)
      "best case" presentations. The AIRP conducts a 4-week Radiologic Pathology
      Correlation Course, which is offered five times per year. On the penultimate day
      of the course, the best case presentation is held at the American Film Institute
      Silver Theater and Cultural Center in Silver Spring, Md. The AIRP faculty
      identifies the best cases, from each organ system, brought by the resident
      attendees. One or more of the best cases from each of the five courses are then
      solicited for publication in RadioGraphics. These cases emphasize the importance
      of radiologic-pathologic correlation in the imaging evaluation and diagnosis of
      diseases encountered at the institute and its predecessor, the Armed Forces
      Institute of Pathology (AFIP).

PMID- 29320333
TI  - Prostate-specific Membrane Antigen PET: Clinical Utility in Prostate Cancer,
      Normal Patterns, Pearls, and Pitfalls.
AB  - Prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein that is
      overexpressed in prostate cancer. Radiolabeled small molecules that bind with
      high affinity to its active extracellular center have emerged as a potential new
      diagnostic standard of reference for prostate cancer, resulting in images with
      extraordinary tumor-to-background contrast. Currently, gallium 68 (68Ga)-PSMA-11
      (or HBED-PSMA) is the most widely used radiotracer for PSMA positron emission
      tomography (PET)/computed tomography (CT) or PSMA PET/magnetic resonance (MR)
      imaging. Evolving evidence demonstrates superior sensitivity and specificity of
      PSMA PET compared to conventional imaging, with frequent identification of
      subcentimeter prostate cancer lesions. PSMA PET is effective for imaging disease
      in the prostate, lymph nodes, soft tissue, and bone in a "one-stop-shop"
      examination. There is emerging evidence for its clinical value in staging of high
      risk primary prostate cancer and localization of disease in biochemical
      recurrence. The high sensitivity provided by PSMA PET, with frequent
      identification of small-volume disease, is redefining patterns of disease spread
      compared with those seen at conventional imaging. In metastatic castration
      resistant prostate cancer, PSMA PET is frequently used for theranostic selection
      (eg, lutetium 177-PSMA radionuclide therapy), but its potential use for therapy
      monitoring is still under debate. However, evidence on its proper use to improve
      patient-related outcomes, particularly in the setting of early biochemical
      recurrence and targeted treatment of oligometastatic disease, is still missing.
      Despite the term prostate specific, PSMA functions as a folate hydrolase and is
      expressed in a range of normal tissues and in other benign and malignant
      processes. Knowledge of its physiologic distribution and other causes of uptake
      is essential to minimize false-positive imaging findings. (c)RSNA, 2018.

PMID- 29320334
TI  - Body Weight and Bullying Victimization among US Adolescents.
AB  - OBJECTIVE: We examined the association between body weight status at all levels
      (including underweight, normal weight, overweight, and obesity) and bullying
      victimization among US ado- lescents using a nationally representative data.
      METHODS: We used logistic regression to exam- ine the association between
      bullying victimization and body weight status by sex with the data from the 2013
      Youth Risk Behavior Survey (YRBS) (N = 11,825), controlling for demographics,
      selected behavioral confounders, and complex survey design. RESULTS: We found a
      statistically significant U-shaped association between body weight and bullying
      victimization among male (p = .001) but not female students (p = .838). For
      girls, the prevalence of being bullied slightly increased from underweight
      (33.58%) to normal weight (34.36%) to obesity (36.18%) but such increases failed
      to reach statistical significance. For boys, being bullied was significantly
      associ- ated with younger age, being white, feeling hopeless, having suicidal
      ideation, and excessive video-game playing. CONCLUSIONS: A U-shaped association
      between body weight and bullying victimization appears to exist in boys but not
      girls, partly because of the body weight stigma and sex stereotypes among US
      adolescents. Future studies should investigate the risk factors associated with
      sex-specific bullying to develop effective anti-bullying programs for youth.

PMID- 29320336
TI  - Knowledge Gaps of the Health Benefits of Beans among Low-Income Women.
AB  - OBJECTIVES: We determined knowledge of the health benefits of consuming beans,
      and assessed if awareness varied by acculturation status among Hispanic and non
      Hispanic low-income women. METHODS: We used a self-administered survey with Iowa
      women aged 18-65 years who were eligible to receive income-based services through
      2 healthcare clinics, a WIC clinic, and Extension Outreach. Chi-square and ANOVA
      were used to compare bean health benefit knowledge, demographics, health-risk
      factors, nutrition information seeking, and self-efficacy by acculturation
      categories. RESULTS: Of the 158 women who completed the survey, 58% were
      Hispanic, with a mean age of 36 years. In terms of acculturation, 24% were
      Hispanic-dominant, 30% bicultural, and 46% English dominant. Over 50% of all
      respondents did not know bean consumption lowered cholesterol, aided blood
      glucose control, or reduced some cancer risks. Responses for 5 of 7 knowledge
      statements differed significantly by acculturation. Hispanic-dominant and
      bicultural women reported significantly better health, higher bean consumption,
      and less cigarette smoking than English-dominant women. Bicultural and English
      dominant women were more likely to use the Internet for nutrition information.
      CONCLUSIONS: There are knowledge gaps about the health benefits of bean
      consumption among low-income women. Nutrition education to improve their
      knowledge may lead to increased bean consumption, reducing health disparities and
      improving nutrition.

PMID- 29320335
TI  - Physician Intervention and Chinese Americans' Colorectal Cancer Screening.
AB  - OBJECTIVE: We conducted a cluster-randomized trial evaluating an intervention
      that trained Chinese-American primary care physicians to increase their Chinese
      patients' colorectal cancer (CRC) screening. METHODS: Twenty-five physicians (13
      randomized to the intervention arm and 12 to the control arm) and 479 of their
      patients (aged 50-75 and nonadherent to CRC screening guidelines) were enrolled.
      The intervention, guided by Social Cognitive Theory, included a communication
      guide and 2 in-office training sessions to enhance physicians' efficacy in com-
      municating CRC screening with patients. Patients' CRC screening rates (trial
      outcome) and rating of physician communication before intervention and at 12
      month follow-up were assessed. Intention-to-treat analysis for outcome evaluation
      was conducted. RESULTS: Screening rates were slightly higher in the intervention
      vs. the control arm (24.4% vs. 17.7%, p = .24). In post hoc analyses,
      intervention arm patients who perceived better communication were more likely to
      be screened than those who did not (OR = 1.09, 95% CI: 1.03, 1.15). This
      relationship was not seen in the control arm. CONCLUSIONS: This physician-focused
      intervention had small, non-significant effects in increasing Chinese patients'
      CRC screening rates. Physician communication appeared to explain intervention
      efficacy. More intensive interventions are needed to enhance Chinese patients'
      CRC screening.

PMID- 29320337
TI  - Improving Resiliency in Healthcare Employees.
AB  - OBJECTIVES: The high prevalence of stress at the workplace has been well
      documented; however, few studies have investigated the efficacy of worksite
      resiliency programs. Therefore, the objec- tive of this project was to examine
      the impact of a worksite resilience training program on improving resiliency and
      health behaviors in healthcare employees. METHODS: Between 2012 and 2016, 137
      adult wellness center members of a healthcare institution participating in a
      single-arm cohort study of a 12-week resiliency training program were assessed at
      baseline, end of intervention, and at 3-month follow-up. RESULTS: Statistically
      significant (p <= .01) improvements were seen at the end of the intervention and
      extending to 3 months follow-up for resiliency, perceived stress, anxiety level,
      quality of life, and health behaviors. CONCLUSIONS: These results support the
      premise that worksite programs designed to improve resiliency in healthcare
      employees have efficacy in improving resiliency, quality of life and health
      behaviors. Given the importance of stress and burnout in healthcare employees,
      future randomized studies are warranted to determine more clearly the impacts of
      this type of resiliency intervention for improving the wellness of healthcare
      workers.

PMID- 29320338
TI  - Healthy Behaviors and Incidence of Disability in Community-Dwelling Elderly.
AB  - OBJECTIVES: In this paper and prospective study, we examine the number of healthy
      behaviors and the incidence of disability in community-dwelling older adults aged
      65 years and older. METHODS: Participants (N = 4483) were residents of Obu, Japan
      who were asked about regular exercise, smoking status, and sleep duration.
      Demographic variables, history of disease, physi- cal function, and cognitive
      function were measured as confounders. Information about disabil- ity was
      obtained from the Obu City Office. RESULTS: At 24 months after baseline
      assessment, 165 participants (3.7%) were certified as having disability.
      Participants with 2 healthy behaviors had a 1.61-fold increased risk of
      disability (95% CI: 1.08 -2.42) compared with those with 3 healthy behaviors;
      those with one or no healthy behaviors had a 2.01-fold risk (95% CI: 1.26-3.19)
      even though adjusting for confounders. CONCLUSIONS: The number of healthy
      behaviors was associated with the incidence of disability, with the hazard ratios
      increasing progressively as the number of healthy behaviors decreased.

PMID- 29320339
TI  - Dental Visits Mediate the Impact of Smoking on Oral Health.
AB  - OBJECTIVES: We explored the mediational relationships among smoking, dental
      visits, and oral health in a longitudinal study. METHODS: We selected a sample of
      adult residents of rural communities of North Central Florida and followed them
      for 3 years (final N = 1170). We examined the impact of smoking on oral health
      across time and conducted mediation analysis to quantify the effect of dental
      visits on the relationship between smoking and poor oral health. RESULTS: Our
      results showed that oral health declined across time for smokers but not for
      nonsmokers. The mediation analysis found that 18.3% of the difference in followup
      oral health between smokers and non-smokers was explained by smokers not having
      any dental visits in the last year. CONCLUSIONS: Our findings suggest that, given
      the low success rate of quitting smoking, promoting dental visits can help limit
      the negative effects of smoking on oral health. Future community prevention
      studies could encourage dental visits among smokers and provide educational
      materials that aim to increase knowledge of oral self-care.

PMID- 29320340
TI  - Lung Cancer Screening Uncertainty among Patients Undergoing LDCT.
AB  - OBJECTIVES: Lung cancer is the leading cause of cancer death, yet lung screening
      remains underutilized. Lung cancer screening uncertainty (LCSU), including
      referral clarity and the perceived accuracy of screening, may hinder utilization
      and represent an unmet psychosocial need. This study sought to identify
      correlates of LCSU among lung screening patients. METHODS: Current and former
      smokers (N = 169) completed questionnaires assessing LCSU, sociodemographic
      variables, objective and subjective numeracy, stress, and anxiety, as part of a
      cross-sectional study of lung screening patients at an academic hospital.
      RESULTS: Patients (52% current smok- ers) reported high clarity about the reason
      for their lung screening referral. Less clarity was as- sociated with lower
      education, not receiving Medicare, and greater stress and anxiety. Patients
      perceived lung screening to be moderately accurate, and levels were inversely
      related to objective numeracy. Subjective numeracy was higher among former versus
      current smokers (OR = 2.5), yet was unrelated to LCSU variables. CONCLUSIONS:
      Several sociodemographic, numeracy, and emotional factors were associated with
      greater LCSU. With multiple policy and clinical guidelines purporting the uptake
      of annual lung screening, it is important to identify patients with LCSU and
      tailor shared decision-making to clarify their uncertainties.

PMID- 29320341
TI  - Long-term Weight Maintenance after Successful Weight Loss: Motivational Factors,
      Support, Difficulties, and Success Factors.
AB  - OBJECTIVES: The main aims of this study were to assess motivational factors for
      weight loss, and support and difficulties during the weight loss and weight
      maintenance phase. METHODS: This study was based upon findings from the Finnish
      Weight Control Registry (FWCR), including 158 formerly obese persons, who lost at
      least 10% of their initial weight and maintained it for at least 2 years. Data
      have been collected through electronic forms. RESULTS: The 2 most commonly
      reported motivational factors for weight loss were health- and appearance-related
      factors. Women reported dissatisfaction with their body more commonly than men (p
      = .023), whereas men reported health-related reasons (p = .008) more often. The
      majority (58%) reported losing weight alone, without any outside support, men
      more commonly than women (p = .006). Persons reported fewer difficulties during
      the maintenance than during the weight loss phase. CONCLUSIONS: Various
      motivational factors for losing weight may lead to successful weight loss and
      long-term weight maintenance. Marked sex differences were reported in relation to
      difficul- ties and need for support.

PMID- 29320342
TI  - Factors Associated with Sunbed use in Women: the E3N-SunExp Study.
AB  - OBJECTIVES: In this study, we attempt to describe the profile of sunbed users
      among cancer-free French women. METHODS: E3N is a prospective cohort including
      98,995 French women aged 40- 65 years in 1990. In 2008, a specific UV
      questionnaire was sent to all reported skin cancer cases and 3 controls per case,
      matched on age, county of birth, and education. We used logistic regression
      models adjusted for pigmentary traits. RESULTS: Compared with non-users, ever
      users of sunbeds were younger (ptrend < .0001), had higher levels of education
      (ptrend = .0004) and income (ptrend = .002), and were more likely to be
      divorced/separated (OR = 1.58). They were more likely to be smokers (OR = 1.59)
      or former smokers (OR = 1.64), had higher alcohol intakes (ptrend = .001), and
      lower physical activity levels (OR = 0.54), although they had a lower BMI (ptrend
      = .004) and a thinner body shape (ptrend = .006). Sunbed users were also more
      likely to report many freckles (ptrend = .01) and sunburns in adulthood (ptrend =
      .008), to use sunscreen (SPF<8: OR = 2.15), and to renew sunscreen application
      (sometimes: OR = 1.49). CONCLUSIONS: Sunbed use is associated with intentional
      sun exposure and several unhealthy behaviors. Our findings call for further re-
      search towards the development of targeted prevention campaigns to reduce sunbed
      use.

PMID- 29320343
TI  - Healthcare Satisfaction among Older Adults.
AB  - OBJECTIVE: This study seeks to examine how older adults rate and identify the
      importance of attributes associated with healthcare seeking and utilization (eg,
      affordability, type of facility, and accessibility) in the United States.
      METHODS: The empirical work of this cross-sectional study is based on the 2014
      Health and Retirement Study. Conjoint analysis and cluster analysis are used to
      assess the objective. RESULTS: There is a pressing need for sound policies that
      seek to reduce the cost of treatment and consultation and to improve the
      accessibility of care facility for older adults even though satisfaction
      pertaining to these attributes (ie, affordability, type of facility, and
      accessibility) differs across clusters. CONCLUSION: The use of conjoint analysis
      in conjunction with cluster analysis can serve as a needs assessment tool to help
      policymakers and practitio- ners gauge older adults' expectations and priorities
      with respect to healthcare seeking and utilization. By taking the priorities of
      older adults into account, policymakers and practitioners can allocate healthcare
      resources more efficiently within budgetary constraints as they redesign and
      customize their program delivery approaches to meet the specific and relative
      healthcare needs of older adults in different clusters.

PMID- 29320344
TI  - A Profile of Individuals with Anti-tobacco Message Fatigue.
AB  - OBJECTIVES: Message fatigue, a phenomenon of being tired of repeated exposure to
      messages promoting the same health behavior, may reduce the effectiveness of anti
      tobacco messages, such as warning labels. As an initial step towards
      understanding the phenomenon, we examined predictors of anti-tobacco message
      fatigue. METHODS: An online study (N = 1838) involving a non-probability sample
      of nonsmokers and smokers in the United States assessed anti-tobacco message
      fatigue and individual-level factors including demographic variables and smoking
      status. General linear models were used to analyze the data. RESULTS: The
      multivariable results show that individuals who were younger, male, and had
      higher income and education reported higher levels of anti-tobacco message
      fatigue. African Americans reported significantly lower levels of message fatigue
      than other racial groups. Current smokers reported greater message fatigue than
      transitioning smokers and nonsmokers. Among current smokers, those with greater
      nicotine dependence reported higher levels of anti-tobacco message fatigue.
      CONCLUSIONS: These findings underscore the importance of segmenting the audience
      based on their levels of message fatigue and using more novel message strategies
      and delivery methods to influence populations with relatively higher levels of
      anti-tobacco message fatigue.

PMID- 29320345
TI  - An Examination of Changes in Social Disparities in Health Behaviors in the US,
      2003-2015.
AB  - OBJECTIVES: Due to growing health disparities, federal and philanthropic agencies
      have empha-sized reducing health disparities in their preventive health efforts.
      This study determined the status of disparities in health behaviors in the last
      13 years in the United States. METHODS: Data were obtained from the Behavioral
      Risk Factor Surveillance Systems in odd years (2003-2015). Health behaviors were
      dichotomized to reflect met fruit and vegetable (FV) consumption and physical
      activity (PA) recommendations, non-cigarette smoking, non-heavy drinking, and non
      binge drinking. Overall and sociodemographic characteristic-specific disparities
      ratios for each behavior were calculated. Linear trend analyses were calculated
      to determine disparities change across the years. RESULTS: Overall disparities
      fluctuated across the years. Linear trend analyses confirmed that education
      specific and income-specific disparities' contribution to overall disparities
      increased for all behaviors. Sex-specific disparities' contribution decreased for
      all behaviors except non-cigarette smoking. Age-specific disparities'
      contribution decreased for all behaviors except non-binge drinking.
      Race/ethnicity-specific disparities' contribution to overall disparities
      increased for FV and non-cigarette smoking, but decreased for the other
      behaviors. CONCLUSIONS: The results suggest health disparities in preventive
      health behaviors in the last 13 years have not improved. Tailored interventions,
      systemic and policy changes, and/or inclusive population efforts should be
      initiated to reduce disparities in preventive health for the most- divergent
      groups identified in the results.

PMID- 29320346
TI  - Media Devices in Parents' and Children's Bedrooms and Children's Media Use.
AB  - OBJECTIVES: The American Academy of Pediatrics advises having no media devices in
      children's bedrooms. We examined the link between media devices in parents' and
      children's bedrooms and children's media use. METHODS: Ninety parent-child dyads
      participated in a community- based healthy weight management study targeting 8-to
      12-year-olds with body mass index (BMI)-for-age >=75th percentile. Parents and
      children reported the number of media devices in their bedrooms and hours spent
      using media devices on weekdays and weekend days. RESULTS: Most children (61%)
      and parents (92%) had at least one media device in their bedrooms. The numbers of
      devices in parents' and children's bedrooms were positively correlated. Children
      with no bedroom media devices reported less weekday media use compared to
      children with bedroom devices. A similar non-significant pattern was found for
      children's weekend media use. CONCLUSIONS: Study findings indicate similar media
      devices in the bedrooms of parents and children and a significant association
      between media devices in children's bedrooms and their weekday media use. Efforts
      to reduce media in parent bedrooms may enhance interventions targeting reduction
      of media use among children, especially those with higher BMI.

PMID- 29320347
TI  - Heroin Use and Drug Injection among Youth Also Misusing Prescription Drugs.
AB  - OBJECTIVES: We identified the prevalence of nonmedical prescription drug use and
      its relationship to heroin and injection drug use in 4 nationally representative
      samples of adolescents. METHODS: We used the most recent data (2009-2015) from
      the Youth Risk Behavior Surveillance System (Ntotal= 61,132). Prevalence rates
      and 95% confidence intervals for prescription drug misuse, heroin use, and
      injection drug use were calculated across time points, sex, and race/ethnicity
      subgroups. Using odds ratios, we determined the likelihood of youth reporting
      nonmedical prescription drug use also reporting heroin and drug injection.
      RESULTS: In 2015, one in 6 adolescents reported recent prescription drug misuse.
      High rates of nonmedical prescription drug use persisted or increased among
      Hispanic boys, black boys, and "other" youth, while declining among white youth.
      Youth who used prescription drugs nonmedically at least once were 17.5 times more
      likely to have used heroin (CI: 13.7, 22.4) and 14.6 times more likely to have
      injected drugs (CI: 11.2, 19.2) in their lifetime. CONCLUSIONS: Public health
      programming focused on reducing prescription drug misuse also may reduce youth
      engagement in heroin and/or injection drug use. Preventive efforts to support
      communities of color in reducing rates of prescription drug misuse are crucial.

PMID- 29320348
TI  - Frequency of Breakfast and Physical Fitness among Chinese College Students.
AB  - OBJECTIVE: Although several studies report a relationship between breakfast
      consumption and physical fitness, results are inconsistent and lack evidence in
      young adults. The objective of this study was to investigate the relationship
      between frequency of breakfast consumption and physical fitness among college
      students. METHODS: This cross-sectional study investigated 10,125 Chinese college
      students (6251 male, 3874 female participants) who underwent physical
      examinations in 2015. Breakfast consumption was assessed using a self-reported
      questionnaire. Physical fitness was evaluated by grip strength and 50-meter
      sprint. RESULTS: After adjusting for confounding factors, a significantly
      positive association was observed between frequency of breakfast consumption and
      grip strength (p < .001 for both sexes). Frequent breakfast consumption also was
      associated with faster sprint times in male and female participants (p < .001,
      and .002 respectively). CONCLUSIONS: We found that frequent breakfast consumption
      is significantly associated with higher grip strength and faster sprint times in
      Chinese college students.

PMID- 29320362
TI  - Predictive value of serum gelsolin and Gc globulin in sepsis - a pilot study.
AB  - BACKGROUND: Simultaneous determination of the two main actin scavenger proteins
      in sepsis has not been investigated until now. In our pilot study, we elucidated
      the predictive values of Gc globulin and gelsolin (GSN) in sepsis by comparing
      them to classic laboratory and clinical parameters. METHODS: A 5-day follow-up
      was performed, including 46 septic patients, 28 non-septic patients and 35
      outpatients as controls. Serum Gc globulin and GSN levels were determined by
      automated immune turbidimetric assay on a Cobas 8000/c502 analyzer. Patients were
      retrospectively categorized according to the sepsis-3 definitions, and 14-day
      mortality was also investigated. RESULTS: First-day GSN also differentiated
      sepsis from non-sepsis (AUC: 0.88) similarly to C-reactive protein (AUC: 0.80)
      but was slightly inferior to procalcitonin (PCT) (AUC: 0.98) with a cutoff value
      of GSN at 22.29 mg/L (sensitivity: 83.3%; specificity: 86.2%). Only first-day
      SOFA scores (0.88) and GSN (0.71) distinguished septic survivors from non
      survivors, whereas lactate (0.99), Gc globulin (0.76) and mean arterial pressure
      (MAP) (0.74) discriminated septic shock from sepsis. Logistic regression analyses
      revealed SOFA scores and GSN being significant factors regarding 14-day
      mortality. First-day GSN levels were higher (p<0.05) in septic survivors than in
      non-survivors. Gc globulin levels remained higher (p<0.01) in sepsis when
      compared with septic shock during the follow-up period. CONCLUSIONS: Both serum
      GSN and Gc globulin may have predictive values in sepsis. Considering the small
      sample size of our study, further measurements are needed to evaluate our
      results. Measurement of Gc globulin and GSN maybe useful in assessment of sepsis
      severity and in therapeutic decision-making.

PMID- 29320363
TI  - Performance evaluation of a new automated fourth-generation HIV Ag/Ab combination
      chemiluminescence immunoassay.

PMID- 29320364
TI  - Cardiometabolic effects of psychotropic medications.
AB  - Background Many psychiatric disorders including schizophrenia, bipolar disorder
      and major depression convey an excess burden of cardiovascular morbidity and
      mortality. The medications used to treat these conditions may further adversely
      affect cardiovascular risk and exacerbate health disparities for vulnerable
      populations. There is a clinical need to appreciate the cardiometabolic adverse
      effects of psychotropic medications. Methods This paper reviews the most relevant
      cardiometabolic effects of psychotropic medications, organized around the
      components of metabolic syndrome. When known, the molecular and physiological
      mechanisms underlying any adverse cardiometabolic effects are detailed. Results
      Many commonly used psychotropic medications, particularly antipsychotics, mood
      stabilizers and some antidepressants, have been independently associated with
      cardiometabolic risk factors such as insulin resistance, obesity and
      dyslipidemia. Stimulants, antidepressants that inhibit reuptake of
      norepinephrine, some antipsychotics and valproic acid derivatives may also
      increase blood pressure. Conclusion Understanding, assessing and subsequently
      managing cardiometabolic complications of psychotropic medications are important
      to mitigate the excess cardiovascular morbidity and mortality in the clinical
      populations prescribed psychotropic medications. There is considerable
      variability in risk between medications and individuals. Timely management of
      iatrogenic cardiometabolic effects is critical.

PMID- 29320365
TI  - Association of cord blood ghrelin, leptin and insulin concentrations in term
      newborns with anthropometric parameters at birth.
AB  - BACKGROUND: Ghrelin, leptin and insulin, generally considered as regulators of
      energy homeostasis of the organism may be related to fetal and early postnatal
      growth. Numerous studies have confirmed the presence of these hormones in the
      cells of the fetus indicating their importance in development at early stages of
      life. METHODS: This study analyzed active and total ghrelin by radioimmunoassay
      (RIA), leptin and insulin concentrations by enzyme-linked immunosorbent assay
      (ELISA) in 65 cord blood samples, from term newborns, and measured the birth
      anthropometric parameters [birth weight (BW), head circumference, chest, stomach,
      thigh and arm circumference]. RESULTS: Active ghrelin (AG) concentrations
      correlated negatively with BW, head circumference, stomach and thigh
      circumference. When divided by gender, AG correlated negatively with males' BW,
      stomach and thigh circumference. Females' head circumference correlated
      negatively with AG. Cord leptin correlated positively with arm circumference.
      When divided by gender, cord leptin was positively associated with BW and stomach
      circumference in male newborns and with thigh and arm circumference in female
      newborns. Insulin concentrations tended to correlate positively with BW in male
      newborns. CONCLUSIONS: In summary, it was confirmed that cord blood ghrelin,
      leptin and insulin correlate with anthropometric parameters at birth. This study
      showed a negative correlation of AG with anthropometric parameters, which may
      emphasize that this hormone is an indicator of growth restriction. This is in
      contrast to cord leptin and insulin, which are more connected with overgrowth.
      Taking all the results into consideration, the metabolic status of the fetus and
      newborn is an essential component in understanding the regulation of perinatal
      development.

PMID- 29320366
TI  - Therapeutic efficacy of specific immunotherapy for glioma: a systematic review
      and meta-analysis.
AB  - Although different immunotherapeutic approaches have been developed for the
      treatment of glioma, there is a discrepancy between clinical trials limiting
      their approval as common treatment. So, the current systematic review and meta
      analysis were conducted to assess survival and clinical response of specific
      immunotherapy in patients with glioma. Generally, seven databases were searched
      to find eligible studies. Controlled clinical trials investigating the efficacy
      of specific immunotherapy in glioma were found eligible. After data extraction
      and risk of bias assessment, the data were analyzed based on the level of
      heterogeneity. Overall, 25 articles with 2964 patients were included. Generally,
      mean overall survival did not statistically improve in immunotherapy [median
      difference=1.51; 95% confidence interval (CI)=-0.16-3.17; p=0.08]; however, it
      was 11.16 months higher in passive immunotherapy (95% CI=5.69-16.64; p<0.0001).
      One-year overall survival was significantly higher in immunotherapy groups
      [hazard ratio (HR)=0.69; 95% CI=0.52-0.92; p=0.01]. As the hazard rate in the
      immunotherapy approach was 0.83 of the control group, 2-year overall survival was
      significantly higher in immunotherapy (HR=0.83; 95% CI=0.69-0.99; p=0.04). Three
      year overall survival was significantly higher in immunotherapy as well (HR=0.67;
      95% CI=0.48-0.92; p=0.01). Overall, median progression-free survival was
      significantly higher in immunotherapy (standard median difference=0.323; 95%
      CI=0.110-0.536; p=0.003). However, 1-year progression-free survival was not
      remarkably different between immunotherapy and control groups (HR=0.94; 95%
      CI=0.74-1.18; p=0.59). Specific immunotherapy demonstrated remarkable improvement
      in survival of patients with glioma and could be a considerable choice of
      treatment in the future. Despite the current promising results, further high
      quality randomized controlled trials are required to approve immunotherapeutic
      approaches as the standard of care and the front-line treatment for glioma.

PMID- 29320367
TI  - Antimicrobial and antioxidant activities of two polyketides from lichen
      endophytic fungus Preussia sp.
AB  - Two compounds, compounds 1 and 2, were isolated from Preussia sp. The molecular
      structures of both compounds were elucidated by analyzing one-dimensional (1D)
      and 2D nuclear magnetic resonance data along with high-resolution mass
      spectrometry data. Compound 1 was obtained as novel in structure, and compound 2
      was recently reported elsewhere. Compound 1 did not show antioxidant and
      antimicrobial activities and brine shrimp toxicity, while compound 2 showed
      strong antioxidant activity (DPPH reduction capacity; IC50=3 MUg/mL) and brine
      shrimp toxicity (LD50=50 MUg/mL).

PMID- 29320368
TI  - Pobeguinine: a monoterpene indole alkaloid and other bioactive constituents from
      the stem bark of Nauclea pobeguinii.

PMID- 29320369
TI  - Evidence of beta-antimonene at the Sb/Bi2Se3 interface.
AB  - We report a study of the interface between antimony and the prototypical
      topological insulator Bi2Se3. Scanning tunnelling microscopy measurements show
      the presence of ordered domains displaying a perfect lattice match with bismuth
      selenide. Density functional theory calculations of the most stable atomic
      configurations demonstrate that the ordered domains can be attributed to stacks
      of beta-antimonene.

PMID- 29320370
TI  - Spatial separation of electrons and holes for enhancing the gas-sensing property
      of a semiconductor: ZnO/ZnSnO3 nanorod arrays prepared by a hetero-epitaxial
      growth.
AB  - The construction of semiconductor composites is known as a powerful method used
      to realize the spatial separation of electrons and the holes in them, which can
      result in more electrons or holes and increase the dispersion of oxygen ions
      ([Formula: see text] and O - ) (one of the most critical factors for their gas
      sensing properties) on the surface of the semiconductor gas sensor. In this work,
      using 1D ZnO/ZnSnO3 nanoarrays as an example, which are prepared through a hetero
      epitaxial growing process to construct a chemically bonded interface, the above
      strategy to attain a better semiconductor gas-sensing property has been realized.
      Compared with single ZnSnO3 nanotubes and no-matching ZnO/ZnSnO3 nanoarrays gas
      sensors, it has been proven by x-ray photoelectron spectroscopy and
      photoluminescence spectrum examination that the as-obtained ZnO/ZnSnO3 sensor
      showed a greatly increased quantity of active surface electrons with exceptional
      responses to trace target gases and much lower optimum working temperatures (less
      than about 170  degrees C). For example, the as-obtained ZnO/ZnSnO3 sensor
      exhibited an obvious response and short response/recovery time (less than 10 s)
      towards trace H2S gas (a detection limit down to 700 ppb). The high responses and
      dynamic repeatability observed in these sensors reveal that the strategy based on
      the as-presented electron and hole separation is reliable for improving the gas
      sensing properties of semiconductors.

PMID- 29320371
TI  - Graphene as an active virtually massless top electrode for RF solidly mounted
      bulk acoustic wave (SMR-BAW) resonators.
AB  - Mechanical and electrical losses induced by an electrode material greatly
      influence the performance of bulk acoustic wave (BAW) resonators. Graphene as a
      conducting and virtually massless 2D material is a suitable candidate as an
      alternative electrode material for BAW resonators which reduces electrode induced
      mechanical losses. In this publication we show that graphene acts as an active
      top electrode for solidly mounted BAW resonators (BAW-SMR) at 2.1 GHz resonance
      frequency. Due to a strong decrease of mass loading and its remarkable electronic
      properties, graphene demonstrates its ability as an ultrathin conductive layer.
      In our experiments we used an optimized graphene wet transfer on aluminum nitride
      based solidly mounted resonator devices. We achieved more than a triplication of
      the resonator's quality factor Q and a resonance frequency close to an 'unloaded'
      resonator without metallization. Our results reveal the direct influence of both,
      the graphene quality and the graphene contacting via metal structures, on the
      performance characteristic of a BAW resonator. These findings clearly show the
      potential of graphene in minimizing mechanical losses due to its virtually
      massless character. Moreover, they highlight the advantages of graphene and other
      2D conductive materials for alternative electrodes in electroacoustic resonators
      for radio frequency applications.

PMID- 29320373
TI  - Enhancement of ZnO based flexible nano generators via sol gel technique for
      sensing and energy harvesting applications.
AB  - Zinc oxide (ZnO) is a remarkable inorganic semiconductor with exceptional
      piezoelectric properties compared to other semiconductors. However, in comparison
      to lead-based hazardous piezoelectric materials, its features have undesired
      limitations. Here we report the 5~6 folds enhancement in the piezoelectric
      properties via chemical doping of copper matched to intrinsic ZnO. The flexible
      piezoelectric nanogenerator (F-PENG) device was fabricated using an unpretentious
      solution process of spin coating with other advantages like robust, low weight,
      improved adhesion, and low cost. The devices were used to demonstrate energy
      harvesting from a Standard weight as low as 4 gm and can work as a self-powered
      mass sensor in a broad range of 4 to 100 gm. The device exhibited a novel energy
      harvesting technique from a wind source due to its inherent flexibility. At three
      different velocities (10~30 m/s) and five different angles of attack (0~180
      degrees), the device validated the ability to discern different velocities and
      directions of flow. The device will be useful for mapping the flow of air apart
      from harvesting the energy. The simulation was done to verify the underlining
      mechanism of aerodynamics involved in it.

PMID- 29320372
TI  - A dentin-derived hydrogel bioink for 3D bioprinting of cell laden scaffolds for
      regenerative dentistry.
AB  - Recent studies in tissue engineering have adopted extracellular matrix (ECM)
      derived scaffolds as natural and cytocompatible microenvironments for tissue
      regeneration. The dentin matrix, specifically, has been shown to be associated
      with a host of soluble and insoluble signaling molecules that can promote
      odontogenesis. Here, we have developed a novel bioink, blending printable
      alginate (3% w/v) hydrogels with the soluble and insoluble fractions of the
      dentin matrix. We have optimized the printing parameters and the concentrations
      of the individual components of the bioink for print accuracy, cell viability and
      odontogenic potential. We find that, while viscosity, and hence printability of
      the bioinks, was greater in the formulations containing higher concentrations of
      alginate, a higher proportion of insoluble dentin matrix proteins significantly
      improved cell viability; where a 1:1 ratio of alginate and dentin (1:1 Alg-Dent)
      was most suitable. We further demonstrate high retention of the soluble dentin
      molecules within the 1:1 Alg-Dent hydrogel blends, evidencing renewed
      interactions between these molecules and the dentin matrix post crosslinking.
      Moreover, at concentrations of 100 MUg ml-1, these soluble dentin molecules
      significantly enhanced odontogenic differentiation of stem cells from the apical
      papilla encapsulated in bioprinted hydrogels. In summary, the proposed novel
      bioinks have demonstrable cytocompatibility and natural odontogenic capacity,
      which can be a used to reproducibly fabricate scaffolds with complex three
      dimensional microarchitectures for regenerative dentistry in the future.

PMID- 29320374
TI  - Plasmonic and SERS performances of compound nanohole arrays fabricated by shadow
      sphere lithography.
AB  - Several plasmonic compound nanohole arrays (CNAs), such as triangular nanoholes
      and fan-like nanoholes with multiple nanotips and nanogaps, are designed by a
      simple and efficient shadow sphere lithography technique by tuning the sphere
      mask size, the deposition and azimuthal angles, substrate temperature T S , and
      the number of deposition steps N. Compared with conventional circular nanohole
      arrays, the CNAs show more hot spots and exhibit new transmission speaks.
      Systematic finite-difference time-domain calculations indicate that different
      resonance modes excited by the various shaped and sized nanoholes are responsible
      for the enhanced plasmonic performances of CNAs. Compared to the CNA samples with
      only one circular hole in the unit cell, the Raman scattering intensity of the
      CNA with multiple triangular nanoholes, nanogaps, and nanotips can be enhanced up
      to 5-fold. These CNAs, due to the strong resonance due to the multiple structural
      features, are promising applications as optical filters, plasmonic sensors, and
      surface-enhanced spectroscopies.

PMID- 29320375
TI  - Psychological flexibility mediates the effect of an online-based acceptance and
      commitment therapy for chronic pain: an investigation of change processes.
AB  - One way to improve treatment effects of chronic pain is to identify and improve
      control over mechanisms of therapeutic change. One treatment approach that
      includes a specific proposed mechanism is acceptance and commitment therapy (ACT)
      with its focus on increasing psychological flexibility (PF). The aim of the
      present study was to examine the role of PF as a mechanism of change in ACT. This
      is based on mediation analyses of data from a previously reported randomized
      controlled trial, evaluating the effectiveness of an ACT-based online
      intervention for chronic pain (ACTonPain). We performed secondary analyses on
      pretreatment, posttreatment, and follow-up data from 302 adults, receiving a
      guided (n = 100) or unguided (n = 101) version of ACTonPain, or allocated to the
      waitlist control group (n = 101). Structural equation modelling and a bias
      corrected bootstrap approach were applied to examine the indirect effects of the
      treatment through pretreatment and posttreatment changes in the latent construct
      reflecting PF. The latent construct consisted of data from the Chronic Pain
      Acceptance Questionnaire and the Acceptance and Action Questionnaire. The
      outcomes were pretreatment to follow-up changes in pain interference, anxiety,
      depression, pain, and mental and physical health. Structural equation modelling
      analyses revealed that changes in PF significantly mediated pretreatment to
      follow-up changes in all outcomes in the intervention groups compared with
      waitlist (standardized estimates ranged from I0.16I to I0.69I). Global model fit
      yielded modest but acceptable results. Findings are consistent with the
      theoretical framework behind ACT and contribute to growing evidence, supporting a
      focus on PF to optimize treatment effects.

PMID- 29320376
TI  - Poststroke Headache: An Underdiagnosed Entity?

PMID- 29320377
TI  - Out of the Box.

PMID- 29320378
TI  - An Examination of Fluoxetine for the Treatment of Selective Mutism Using a
      Nonconcurrent Multiple-Baseline Single-Case Design Across 5 Cases.
AB  - This study examined the utility of fluoxetine in the treatment of 5 children,
      aged 5 to 14 years, diagnosed with selective mutism who also demonstrated
      symptoms of social anxiety. A nonconcurrent, randomized, multiple-baseline,
      single-case design with a single-blind placebo-controlled procedure was used.
      Parents and the study psychiatrist completed multiple methods of assessment
      including Direct Behavior Ratings and questionnaires. Treatment outcomes were
      evaluated by calculating effect sizes for each participant as an individual and
      for the participants as a group. Information regarding adverse effects with an
      emphasis on behavioral disinhibition and ratings of parental acceptance of the
      intervention was gathered. All 5 children experienced improvement in social
      anxiety, responsive speech, and spontaneous speech with medium to large effect
      sizes; however, children still met criteria for selective mutism at the end of
      the study. Adverse events were minimal, with only 2 children experiencing brief
      occurrences of minor behavioral disinhibition. Parents found the treatment highly
      acceptable.

PMID- 29320379
TI  - Botulinum Toxin as a Treatment for Depression in a Real-world Setting.
AB  - OBJECTIVES: A series of randomized controlled trials have shown the efficacy of
      glabellar botulinum toxin (BTX) injection as a treatment for depression in women.
      We wanted to extend these findings and assess how they may be translated to a
      real-world setting. METHODS: For that purpose, 42 patients with severe, in most
      cases chronic and treatment-resistant depression received adjunctive treatment
      with BTX in private practice. Depression severity was rated before and 3 weeks
      after the treatment using the Hamilton Depression Rating Scale, the Montgomery
      Asberg Depression Rating Scale, and the Beck Depression Inventory. RESULTS:
      Almost all of the patients improved clinically, with depression scores dropping
      by 27% on all 3 scales in the sample as a whole. These changes were highly
      significant (P<0.001, paired t test or Wilcoxon test) and the absolute prepost
      score differences were similar to those observed in previous randomized
      controlled trials. Importantly, treatment effects did not differ between male
      (n=23) and female (n=19) patients. CONCLUSIONS: These findings suggest that
      glabellar BTX injection may also be effective in the treatment of severe
      depression and in the treatment of depression in men, when treatment is carried
      out not just in clinical trials but in real-world settings.

PMID- 29320380
TI  - Reducing the Risk of Type 2 Diabetes in Nonselected Outpatients With
      Schizophrenia: A 30-Month Program.
AB  - BACKGROUND: Type 2 diabetes is 2- to 3-fold more common in patients with
      schizophrenia than in the general population. A lifestyle with a focus on diet,
      exercise, and medication is required to prevent complications from type 2
      diabetes, but patients with schizophrenia frequently have trouble maintaining
      such a lifestyle because of factors related to their illness, such as cognitive
      disturbances, negative and positive symptoms, and side effects of psychotropic
      medications. OBJECTIVE: To measure and reduce risk factors for type 2 diabetes in
      patients with schizophrenia and examine characteristics associated with positive
      outcomes. METHODS: This study, which was conducted in clinics treating both newly
      diagnosed and long-term (LT) patients with schizophrenia, evaluated the effects
      of a 30-month naturalistic intervention on improvement in the physical health of
      patients treated for schizophrenia and reduction in their risk factors for type 2
      diabetes. The clinical intervention incorporated individual guidance, group
      sessions, and treatment as usual. RESULTS: Patients newly diagnosed with
      schizophrenia were found to have high consumption of soft drinks and low physical
      activity at their index evaluation. At follow-up, the physical profile of these
      patients had worsened, with increased weight, waist circumferences, visceral
      adiposity index (P=0.030), and glycosylated hemoglobin (HbA1c; P=0.010). Average
      HbA1c values increased in newly diagnosed male patients by 0.24 mmol/l (P=0.007).
      At follow-up, LT patients improved with regard to their consumption of soft
      drinks (P=0.001) and fast food (P=0.009). The LT patients also reduced their
      weight and waist circumferences and became more physically active. No changes in
      HbA1c values were found in the LT patients during the intervention period.
      CONCLUSION: The study found that positive outcomes were associated with female
      sex and a longer duration of illness. Negative outcomes with worsening of risk
      factors were associated with being newly diagnosed with schizophrenia and male
      sex. It was possible to produce improvements in some risk factors through
      individual health-oriented lifestyle interventions, especially in LT patients.

PMID- 29320381
TI  - A Brief Interview to Detect Panic Attacks and Panic Disorder in Emergency
      Department Patients with Cardiopulmonary Complaints.
AB  - OBJECTIVES: Patients with panic-related anxiety often initially present to the
      emergency department (ED) complaining of respiratory or cardiac symptoms, but
      rates of detection of panic symptoms by ED physicians remain low. This study was
      undertaken to evaluate the relevance of panic attacks and panic disorder in ED
      patients who present with cardiopulmonary symptoms and to determine whether a
      brief symptom-based tool could be constructed to assist in rapid recognition of
      panic-related anxiety in the ED setting. MATERIALS AND METHODS: English-speaking
      adult ED patients with a chief complaint of palpitations, chest pain, dizziness,
      or difficulty breathing were evaluated for the presence of panic attacks and
      panic disorder with the Structured Clinical Interview for DSM-IV Axis I
      Disorders. Participants completed self-report measures to assess panic-related
      symptoms, comorbid psychiatric conditions, health-related disability, and health
      service use. RESULTS: In this sample (N=200), 23.5% had panic attacks and 23.0%
      had panic disorder. Both groups reported higher rates of panic attack symptoms,
      greater psychiatric comorbidity, greater health-related disability, and higher
      rates of ED and mental health service use compared with those without either
      condition. A brief 7-item tool consisting of panic symptoms identified patients
      with panic attacks or panic disorder with 85% accuracy (area under the
      curve=0.90, sensitivity=82%, specificity=88%). CONCLUSIONS: Patients with panic
      attacks or panic disorder commonly present to the ED, but often go unrecognized.
      A brief 7-item clinician rating scale accurately identifies these patients among
      those ED patients presenting with cardiopulmonary complaints.

PMID- 29320382
TI  - Two New Psychotherapy Studies: Back to the Future?
AB  - This column reviews 2 recent high-quality psychotherapy research studies. One
      study by Steinert and colleagues suggests that psychodynamic therapy is
      equivalent to cognitive behavioral therapy (CBT) (or medication when this was the
      comparator) for a range of disorders. A second study by Barlow and colleagues
      finds Unified Protocol CBT targeting underlying emotional dysregulation to be
      equivalent to single disorder-specific CBT for a range of anxiety disorders.
      Taken together, these studies help bridge the gap between CBT and psychodynamic
      therapy and refocus us on the realities of clinical settings, where most patients
      present with multiple comorbid disorders.

PMID- 29320383
TI  - The Mask of Happiness: Unmasking Coercive Control in Intimate Relationships.
AB  - While most mental health professionals know how to recognize the obvious and most
      concerning presentations of possible intimate partner violence, there are
      numerous ways in which a partner may be controlled, bullied, isolated, exploited,
      and manipulated that do not present such observable signs. The literature
      pertaining to domestic abuse has increasingly moved away from injury as a
      necessary marker and instead has begun to highlight the importance of more covert
      but similarly deleterious processes within certain intimate relationships. It is
      crucial that mental health professionals inform themselves about other ways
      individuals are exploited with or without physical injury to ensure resources are
      made available to those who may be being harmed through manipulation, threats,
      fear, and isolation. This article defines and exemplifies the dynamic of coercive
      control, a more insidious and difficult to identify process of domination and
      exploitation that victims have a hard time labeling on their own. Further reading
      and resources are also provided.

PMID- 29320384
TI  - Cannabinoid Hyperemesis Syndrome and the Consulting Psychiatrist: A Case Study of
      Diagnosis and Treatment for an Emerging Disorder in Psychiatric Practice.
AB  - The increasing prevalence of cannabis use in the United States requires awareness
      of cannabis-related disorders and familiarity with treatment options. We present
      a case of cannabinoid hyperemesis syndrome that required psychiatric consultation
      for diagnostic clarification and effective treatment with intravenous
      haloperidol. Literature from emergency medicine, toxicology, and gastroenterology
      is reviewed, including proposed diagnostic criteria for cannabinoid hyperemesis
      syndrome and reported off-label treatment options, with a specific focus on
      clinical questions facing the practicing psychiatrist regarding this emerging
      disorder.

PMID- 29320385
TI  - Ketamine Use for Suicidal Ideation in the General Hospital: Case Report and Short
      Review.
AB  - Low-dose infusion of ketamine may have rapid antisuicide properties. Such a
      treatment may therefore be useful in the general hospital to prevent suicide in
      an environment that cannot be made safe enough. We report on the use of ketamine
      as an efficient, well-tolerated treatment for persistent suicidal ideation in a
      patient hospitalized in a general hospital after a severe suicide attempt. Based
      on data in the literature, we suggest that the benefit-risk ratio for ketamine
      use in such a context is highly favorable.

PMID- 29320386
TI  - Examining the Feasibility and Acceptability of an Online Yoga Class for Mood
      Disorders: A MoodNetwork Study.
AB  - BACKGROUND: Despite ongoing advances in the treatment of mood disorders, a
      substantial proportion of people diagnosed with major depression or bipolar
      disorder remain symptomatic over time. Yoga, which has been shown to reduce
      stress and depressive symptoms, as well as to improve overall quality of life,
      shows promise as an adjunctive treatment. However, dissemination of yoga for
      clinical populations remains challenging. The purpose of this pilot study was to
      test the feasibility and acceptability of an online yoga intervention for
      individuals with mood disorders. METHODS: In total, 56 adults who reported being
      diagnosed with a mood disorder (bipolar disorder, major depressive disorder,
      cyclothymia, or schizoaffective disorder) were recruited from MoodNetwork, an
      online community of individuals with mood disorders. A feedback survey and a
      measure of positive and negative affect were administered before and after a 30
      minute online Hatha yoga class. RESULTS: In total, 44 individuals (78.6%)
      completed all components of the yoga class. The mean score on a 10-point Likert
      scale rating how much participants liked the online yoga class was 7.24
      (SD=2.40). Most participants (67.9%) reported that they would be "somewhat
      likely" or "very likely" to participate in an online yoga program again. There
      was a statistically significant decrease in negative affect after completing the
      class (t=-6.05; P<0.001), but positive affect did not change (P>0.10).
      DISCUSSION: These preliminary data support the utility of online yoga tailored
      specifically for people with mood disorders as a possible adjunctive intervention
      that warrants further investigation.

PMID- 29320387
TI  - Identification of Inherited Retinal Disease-Associated Genetic Variants in 11
      Candidate Genes.
AB  - Inherited retinal diseases (IRDs) display an enormous genetic heterogeneity.
      Whole exome sequencing (WES) recently identified genes that were mutated in a
      small proportion of IRD cases. Consequently, finding a second case or family
      carrying pathogenic variants in the same candidate gene often is challenging. In
      this study, we searched for novel candidate IRD gene-associated variants in
      isolated IRD families, assessed their causality, and searched for novel genotype
      phenotype correlations. Whole exome sequencing was performed in 11 probands
      affected with IRDs. Homozygosity mapping data was available for five cases.
      Variants with minor allele frequencies <= 0.5% in public databases were selected
      as candidate disease-causing variants. These variants were ranked based on their:
      (a) presence in a gene that was previously implicated in IRD; (b) minor allele
      frequency in the Exome Aggregation Consortium database (ExAC); (c) in silico
      pathogenicity assessment using the combined annotation dependent depletion (CADD)
      score; and (d) interaction of the corresponding protein with known IRD-associated
      proteins. Twelve unique variants were found in 11 different genes in 11 IRD
      probands. Novel autosomal recessive and dominant inheritance patterns were found
      for variants in Small Nuclear Ribonucleoprotein U5 Subunit 200 (SNRNP200) and
      Zinc Finger Protein 513 (ZNF513), respectively. Using our pathogenicity
      assessment, a variant in DEAH-Box Helicase 32 (DHX32) was the top ranked novel
      candidate gene to be associated with IRDs, followed by eight medium and lower
      ranked candidate genes. The identification of candidate disease-associated
      sequence variants in 11 single families underscores the notion that the
      previously identified IRD-associated genes collectively carry > 90% of the
      defects implicated in IRDs. To identify multiple patients or families with
      variants in the same gene and thereby provide extra proof for pathogenicity,
      worldwide data sharing is needed.

PMID- 29320391
TI  - Removal of Expression of Concern: Segneanu et al. Helleborus purpurascens-Amino
      Acid and Peptide Analysis Linked to the Chemical and Antiproliferative Properties
      of the Extracted Compounds. Molecules 2015, 20, 22170-22187.
AB  - The article [1] published in Molecules was the subject of a law suit related to
      authorship. We previously published an Expression of Concern to highlight this
      fact to readers[...].

PMID- 29320394
TI  - Neurological Respiratory Failure.
AB  - West Nile virus infection in humans is mostly asymptomatic. Less than 1% of neuro
      invasive cases show a fatality rate of around 10%. Acute flaccid paralysis of
      respiratory muscles leading to respiratory failure is the most common cause of
      death. Although the peripheral nervous system can be involved, isolated phrenic
      nerve palsy leading to respiratory failure is rare and described in only two
      cases in the English literature. We present another case of neurological
      respiratory failure due to West Nile virus-induced phrenic nerve palsy. Our case
      reiterates the rare, but lethal, consequences of West Nile virus infection, and
      the increase of its awareness among physicians.

PMID- 29320389
TI  - Sponges: A Reservoir of Genes Implicated in Human Cancer.
AB  - Recently, it was shown that the majority of genes linked to human diseases, such
      as cancer genes, evolved in two major evolutionary transitions-the emergence of
      unicellular organisms and the transition to multicellularity. Therefore, it has
      been widely accepted that the majority of disease-related genes has already been
      present in species distantly related to humans. An original way of studying human
      diseases relies on analyzing genes and proteins that cause a certain disease
      using model organisms that belong to the evolutionary level at which these genes
      have emerged. This kind of approach is supported by the simplicity of the
      genome/proteome, body plan, and physiology of such model organisms. It has been
      established for quite some time that sponges are an ideal model system for such
      studies, having a vast variety of genes known to be engaged in sophisticated
      processes and signalling pathways associated with higher animals. Sponges are
      considered to be the simplest multicellular animals and have changed little
      during evolution. Therefore, they provide an insight into the metazoan ancestor
      genome/proteome features. This review compiles current knowledge of cancer
      related genes/proteins in marine sponges.

PMID- 29320395
TI  - Using Acceleration Data to Automatically Detect the Onset of Farrowing in Sows.
AB  - The aim of the present study was to automatically predict the onset of farrowing
      in crate-confined sows. (1) Background: Automatic tools are appropriate to
      support animal surveillance under practical farming conditions. (2) Methods: In
      three batches, sows in one farrowing compartment of the Futterkamp research farm
      were equipped with an ear sensor to sample acceleration. As a reference video,
      recordings of the sows were used. A classical CUSUM chart using different
      acceleration indices of various distribution characteristics with several
      scenarios were compared. (3) Results: The increase of activity mainly due to nest
      building behavior before the onset of farrowing could be detected with the sow
      individual CUSUM chart. The best performance required a statistical distribution
      characteristic that represented fluctuations in the signal (for example, 1st
      variation) combined with a transformation of this parameter by cumulating
      differences in the signal within certain time periods from one day to another.
      With this transformed signal, farrowing sows could reliably be detected. For 100%
      or 85% of the sows, an alarm was given within 48 or 12 h before the onset of
      farrowing. (4) Conclusions: Acceleration measurements in the ear of a sow are
      suitable for detecting the onset of farrowing in individually housed sows in
      commercial farrowing crates.

PMID- 29320397
TI  - In Silico Analysis of the Association Relationship between Neuroprotection and
      Flavors of Traditional Chinese Medicine Based on the mGluRs.
AB  - The metabotropic glutamate receptors (mGluRs) are known as both synaptic
      receptors and taste receptors. This feature is highly similar to the Property and
      Flavor theory of Traditional Chinese medicine (TCM), which has the
      pharmacological effect and flavor. In this study, six ligand based pharmacophore
      (LBP) models, seven homology modeling models, and fourteen molecular docking
      models of mGluRs were built based on orthosteric and allosteric sites to
      screening potential compounds from Traditional Chinese Medicine Database (TCMD).
      Based on the Pharmacopoeia of the People's Republic of China, TCMs of compounds
      and their flavors were traced and listed. According to the tracing result, we
      found that the TCMs of the compounds which bound to orthosteric sites of mGluRs
      are highly correlated to a sweet flavor, while the allosteric site corresponds to
      a bitter flavor. Meanwhile, the pharmacological effects of TCMs with highly
      frequent flavors were further analyzed. We found that those TCMs play a
      neuroprotective role through the efficiencies of detumescence, promoting blood
      circulation, analgesic effect, and so on. This study provides a guide for
      developing new neuroprotective drugs from TCMs which target mGluRs. Moreover, it
      is the first study to present a novel approach to discuss the association
      relationship between flavor and the neuroprotective mechanism of TCM based on
      mGluRs.

PMID- 29320399
TI  - On Farm Evaluation of a Novel Mechanical Cervical Dislocation Device for Poultry.
AB  - Urgent development of alternative on-farm killing methods for poultry is required
      following the number restrictions placed on the use of traditional manual
      cervical dislocation by European Legislation (EU 1099/2009). Alternatives must be
      proven to be humane and, crucially, practical in commercial settings with
      multiple users. We assessed the performance and reliability of a novel mechanical
      cervical dislocation device (NMCD) compared to the traditional manual cervical
      dislocation (MCD) method. NMCD was based on a novel device consisting of a thin
      supportive glove and two moveable metal finger inserts designed to aid the
      twisting motion of cervical dislocation. We employed a 2 * 2 factorial design,
      with a total of eight stockworkers from broiler and layer units (four per farm)
      each killing 70 birds per method. A successful kill performance was defined as
      immediate absence of rhythmic breathing and nictitating membrane reflex; a
      detectable gap in the vertebrae and only one kill attempt (i.e., one stretch and
      twist motion). The mean stockworker kill performance was significantly higher for
      MCD (98.4 +/- 0.5%) compared to NMCD (81.6 +/- 1.8%). However, the MCD technique
      normally used by the stockworkers (based previous in-house training received)
      affected the performance of NMCD and was confounded by unit type (broilers), with
      the majority of broiler stockworkers trained in a non-standard technique, making
      adaption to the NMCD more difficult. The consistency of trauma induced by the
      killing methods (based on several post-mortem parameters) was higher with NMCD
      demonstrated by "gold standard" trauma achieved in 30.2% of birds, compared to
      11.4% for MCD (e.g., dislocation higher up the cervical region of the spine i.e.,
      between vertebrae C0-C1, >=1 carotid arteries severed), suggesting it has the
      potential to improve welfare at killing. However, the results also suggest that
      the NMCD method requires further refinement and training optimization in order
      for it to be acceptable as an alternative across poultry industry, irrespective
      of previous MCD technique and training.

PMID- 29320400
TI  - Posidonia oceanica (L.) Delile Ethanolic Extract Modulates Cell Activities with
      Skin Health Applications.
AB  - Seagrasses are high plants sharing adaptive metabolic features with both
      terrestrial plants and marine algae, resulting in a phytocomplex possibly endowed
      with interesting biological properties. The aim of this study is to evaluate the
      in vitro activities on skin cells of an ethanolic extract obtained from the
      leaves of Posidonia oceanica (L.) Delile, family Potamogetonaceae, herein named
      Posidonia ethanolic extract (PEE). PEE showed high radical scavenging activity,
      high phenolic content, and resulted rich in chicoric acid, as determined through
      HPLC-MS analysis. The use of MTT assay on fibroblasts showed a PEE cytotoxicity
      threshold (IC05) of 50 ug/mL at 48 h, while a sub-toxic dose of 20 ug/mL induced
      a significant increase of fibroblast growth rate after 10 days. In addition, an
      ELISA assay revealed that PEE doses of 5 and 10 ug/mL induced collagen production
      in fibroblasts. PEE induced dose-dependent mushroom tyrosinase inhibition, up to
      about 45% inhibition at 1000 ug/mL, while 50% reduction of melanin was observed
      in melanoma cells exposed to 50 ug/mL PEE. Finally, PEE lipolytic activity was
      assessed by measuring glycerol release from adipocytes following triglyceride
      degradation. In conclusion, we have collected new data about the biological
      activities of the phytocomplex of P. oceanica seagrass on skin cells. Our
      findings indicate that PEE could be profitably used in the development of
      products for skin aging, undesired hyperpigmentation, and cellulite.

PMID- 29320401
TI  - Mediterranean Diet and Other Dietary Patterns in Primary Prevention of Heart
      Failure and Changes in Cardiac Function Markers: A Systematic Review.
AB  - BACKGROUND: Heart failure (HF) is a complex syndrome and is recognized as the
      ultimate pathway of cardiovascular disease (CVD). Studies using nutritional
      strategies based on dietary patterns have proved to be effective for the
      prevention and treatment of CVD. Although there are studies that support the
      protective effect of these diets, their effects on the prevention of HF are not
      clear yet. METHODS: We searched the Medline, Embase, and Cochrane databases for
      studies that examined dietary patterns, such as dietary approaches to stop
      hypertension (DASH diet), paleolithic, vegetarian, low-carb and low-fat diets and
      prevention of HF. No limitations were used during the search in the databases.
      RESULTS: A total of 1119 studies were identified, 14 met the inclusion criteria.
      Studies regarding the Mediterranean, DASH, vegetarian, and Paleolithic diets were
      found. The Mediterranean and DASH diets showed a protective effect on the
      incidence of HF and/or worsening of cardiac function parameters, with a
      significant difference in relation to patients who did not adhere to these
      dietary patterns. CONCLUSIONS: It is observed that the adoption of Mediterranean
      or DASH-type dietary patterns may contribute to the prevention of HF, but these
      results need to be analyzed with caution due to the low quality of evidence.

PMID- 29320403
TI  - Bacillibactin and Bacillomycin Analogues with Cytotoxicities against Human Cancer
      Cell Lines from Marine Bacillus sp. PKU-MA00093 and PKU-MA00092.
AB  - Nonribosomal peptides from marine Bacillus strains have received considerable
      attention for their complex structures and potent bioactivities. In this study,
      we carried out PCR-based genome mining for potential nonribosomal peptides
      producers from our marine bacterial library. Twenty-one "positive" strains were
      screened out from 180 marine bacterial strains, and subsequent small-scale
      fermentation, HPLC and phylogenetic analysis afforded Bacillus sp. PKU-MA00092
      and PKU-MA00093 as two candidates for large-scale fermentation and isolation. Ten
      nonribosomal peptides, including four bacillibactin analogues (1-4) and six
      bacillomycin D analogues (5-10) were discovered from Bacillus sp. PKU-MA00093 and
      PKU-MA00092, respectively. Compounds 1 and 2 are two new compounds and the 1H NMR
      and 13C NMR data of compounds 7 and 9 is first provided. All compounds 1-10 were
      assayed for their cytotoxicities against human cancer cell lines HepG2 and MCF7,
      and the bacillomycin D analogues 7-10 showed moderate cytotoxicities with IC50
      values from 2.9 +/- 0.1 to 8.2 +/- 0.2 uM. The discovery of 5-10 with different
      fatty acid moieties gave us the opportunity to reveal the structure-activity
      relationships of bacillomycin analogues against these human cancer cell lines.
      These results enrich the structural diversity and bioactivity properties of
      nonribosomal peptides from marine Bacillus strains.

PMID- 29320404
TI  - Anchoring ZnO Nanoparticles in Nitrogen-Doped Graphene Sheets as a High
      Performance Anode Material for Lithium-Ion Batteries.
AB  - A novel binary nanocomposite, ZnO/nitrogen-doped graphene (ZnO/NG), is
      synthesized via a facile solution method. In this prepared ZnO/NG composite,
      highly-crystalline ZnO nanoparticles with a size of about 10 nm are anchored
      uniformly on the N-doped graphene nanosheets. Electrochemical properties of the
      ZnO/NG composite as anode materials are systematically investigated in lithium
      ion batteries. Specifically, the ZnO/NG composite can maintain the reversible
      specific discharge capacity at 870 mAh g-1 after 200 cycles at 100 mA g-1.
      Besides the enhanced electronic conductivity provided by interlaced N-doped
      graphene nanosheets, the excellent lithium storage properties of the ZnO/NG
      composite can be due to nanosized structure of ZnO particles, shortening the Li+
      diffusion distance, increasing reaction sites, and buffering the ZnO volume
      change during the charge/discharge process.

PMID- 29320402
TI  - The Secretory Response of Rat Peritoneal Mast Cells on Exposure to Mineral
      Fibers.
AB  - BACKGROUND: Exposure to mineral fibers is of substantial relevance to human
      health. A key event in exposure is the interaction with inflammatory cells and
      the subsequent generation of pro-inflammatory factors. Mast cells (MCs) have been
      shown to interact with titanium oxide (TiO2) and asbestos fibers. In this study,
      we compared the response of rat peritoneal MCs challenged with the asbestos
      crocidolite and nanowires of TiO2 to that induced by wollastonite employed as a
      control fiber. METHODS: Rat peritoneal MCs (RPMCs), isolated from peritoneal
      lavage, were incubated in the presence of mineral fibers. The quantities of
      secreted enzymes were evaluated together with the activity of fiber-associated
      enzymes. The ultrastructural morphology of fiber-interacting RPMCs was analyzed
      with electron microscopy. RESULTS: Asbestos and TiO2 stimulate MC secretion.
      Secreted enzymes bind to fibers and exhibit higher activity. TiO2 and
      wollastonite bind and improve enzyme activity, but to a lesser degree than
      crocidolite. CONCLUSIONS: (1) Mineral fibers are able to stimulate the mast cell
      secretory process by both active (during membrane interaction) and/or passive
      (during membrane penetration) interaction; (2) fibers can be found to be
      associated with secreted enzymes-this process appears to create long-lasting pro
      inflammatory environments and may represent the active contribution of MCs in
      maintaining the inflammatory process; (3) MCs and their enzymes should be
      considered as a therapeutic target in the pathogenesis of asbestos-induced lung
      inflammation; and (4) MCs can contribute to the inflammatory effect associated
      with selected engineered nanomaterials, such as TiO2 nanoparticles.

PMID- 29320405
TI  - Effect of shRNA Mediated Silencing of YB-1 Protein on the Expression of Matrix
      Collagenases in Malignant Melanoma Cell In Vitro.
AB  - Background and Objective: YB-1 is a transcription and oncogenic factor capable of
      binding to DNA and RNA performing versatile functions within normal and cancer
      cells. Some studies reported the binding of YB-1 with a collagenases gene
      promoter and influencing their expression. In addition, the role of YB-1 in
      malignant melanoma was not elucidated. Thus, in this study, the aim was to knock
      down the expression of YB-1 in A375 malignant melanoma cancer cell using the
      shRNA approach and study its effect on cancer cell proliferation, migration, and
      expression of collagenases. Methods: A375 malignant melanoma cell lines were
      grown in standard conditions and were transfected with three plasmids containing
      a retroviral pGFP-V-RS vector, two of them containing targeting sequences for YB
      1 mRNA. The third plasmid contained a scrambled mRNA sequence as a negative
      control. Expression of YB-1 was validated using immune-fluorescence staining, RT
      PCR and western blotting. The cancer cell proliferation was determined using MTT
      assay, serial trypan blue cell counting and cell cycle flow-cytometry analysis.
      Expression of collagenases (MMP1, MMP8, and MMP13) was evaluated using RT-PCR and
      western blotting analysis. In addition, a wound-healing assay was used to assess
      cell migration potential. Statistical analysis was performed using one-way ANOVA
      test with Bonferroni post hoc analysis to compare the quantitative results among
      samples. Results: The established silenced cell strains (P1 and P2) had nearly
      70% knockdown in the expression of YB-1. These YB-1 silenced strains had a
      significant cell cycle-specific reduction in cell proliferation (p < 0.05 in
      serial cell counting and cell cycle flow cytometry analysis, p < 0.001 in MTT
      assay). In addition, YB-1 silenced strains had a remarkable reduction in cell
      migration potential. Expression of MMP13 was significantly reduced in YB-1
      silenced strains. Conclusion: YB-1 oncoprotein is a promising target in the
      treatment of malignant melanoma. Silencing of this protein is associated with
      significant anti-proliferative, anti-invasive and MMP13 insulating properties in
      A375 malignant melanoma cancer cell lines.

PMID- 29320406
TI  - A Police and Insurance Joint Management System Based on High Precision BDS/GPS
      Positioning.
AB  - Car ownership in China reached 194 million vehicles at the end of 2016. The
      traffic congestion index (TCI) exceeds 2.0 during rush hour in some cities.
      Inefficient processing for minor traffic accidents is considered to be one of the
      leading causes for road traffic jams. Meanwhile, the process after an accident is
      quite troublesome. The main reason is that it is almost always impossible to get
      the complete chain of evidence when the accident happens. Accordingly, a police
      and insurance joint management system is developed which is based on high
      precision BeiDou Navigation Satellite System (BDS)/Global Positioning System
      (GPS) positioning to process traffic accidents. First of all, an intelligent
      vehicle rearview mirror terminal is developed. The terminal applies a commonly
      used consumer electronic device with single frequency navigation. Based on the
      high precision BDS/GPS positioning algorithm, its accuracy can reach sub-meter
      level in the urban areas. More specifically, a kernel driver is built to realize
      the high precision positioning algorithm in an Android HAL layer. Thus the third
      party application developers can call the general location Application
      Programming Interface (API) of the original standard Global Navigation Satellite
      System (GNSS) to get high precision positioning results. Therefore, the terminal
      can provide lane level positioning service for car users. Next, a remote traffic
      accident processing platform is built to provide big data analysis and
      management. According to the big data analysis of information collected by BDS
      high precision intelligent sense service, vehicle behaviors can be obtained. The
      platform can also automatically match and screen the data that uploads after an
      accident to achieve accurate reproduction of the scene. Thus, it helps traffic
      police and insurance personnel to complete remote responsibility identification
      and survey for the accident. Thirdly, a rapid processing flow is established in
      this article to meet the requirements to quickly handle traffic accidents. The
      traffic police can remotely identify accident responsibility and the insurance
      personnel can remotely survey an accident. Moreover, the police and insurance
      joint management system has been carried out in Wuhan, Central China's Hubei
      Province, and Wuxi, Eastern China's Jiangsu Province. In a word, a system is
      developed to obtain and analyze multisource data including precise positioning
      and visual information, and a solution is proposed for efficient processing of
      traffic accidents.

PMID- 29320407
TI  - Biodistribution and Clearance of Stable Superparamagnetic Maghemite Iron Oxide
      Nanoparticles in Mice Following Intraperitoneal Administration.
AB  - Nanomedicine is an emerging field with great potential in disease theranostics.
      We generated sterically stabilized superparamagnetic iron oxide nanoparticles (s
      SPIONs) with average core diameters of 10 and 25 nm and determined the in vivo
      biodistribution and clearance profiles. Healthy nude mice underwent an
      intraperitoneal injection of these s-SPIONs at a dose of 90 mg Fe/kg body weight.
      Tissue iron biodistribution was monitored by atomic absorption spectroscopy and
      Prussian blue staining. Histopathological examination was performed to assess
      tissue toxicity. The 10 nm s-SPIONs resulted in higher tissue-iron levels,
      whereas the 25 nm s-SPIONs peaked earlier and cleared faster. Increased iron
      levels were detected in all organs and body fluids tested except for the brain,
      with notable increases in the liver, spleen, and the omentum. The tissue-iron
      returned to control or near control levels within 7 days post-injection, except
      in the omentum, which had the largest and most variable accumulation of s-SPIONs.
      No obvious tissue changes were noted although an influx of macrophages was
      observed in several tissues suggesting their involvement in s-SPION sequestration
      and clearance. These results demonstrate that the s-SPIONs do not degrade or
      aggregate in vivo and intraperitoneal administration is well tolerated, with a
      broad and transient biodistribution. In an ovarian tumor model, s-SPIONs were
      shown to accumulate in the tumors, highlighting their potential use as a
      chemotherapy delivery agent.

PMID- 29320409
TI  - Evaluating the Impact of a Clinician Improvement Program for Treating Patients
      with Intellectual and Developmental Disabilities: The Challenging Case of
      Mississippi.
AB  - In recent years, people with intellectual and developmental disabilities (IDD)
      have moved from institutionalized settings to local community residences. While
      deinstitutionalization has yielded quality of life improvements for people with
      IDD, this transition presents significant health-related challenges. Community
      clinicians have typically not been trained to provide sound medical care to
      people with IDD, a subpopulation that exhibits unique medical needs and
      significant health disparities. This study reports the results of a comprehensive
      evaluation of an IDD-focused clinician improvement program implemented throughout
      Mississippi. DETECT (Developmental Evaluation, Training and Consultative Team)
      was formed to equip Mississippi's physicians and nurses to offer competent
      medical care to people with IDD living in community residences. Given the state's
      pronounced health disparities and its clinician shortage, Mississippi offers a
      stringent test of program effectiveness. Results of objective survey indicators
      and subjective rating barometers administered before and after clinician
      educational seminars reveal robust statistically significant differences in
      clinician knowledge and self-assessed competence related to treating people with
      IDD. These results withstand controls for various confounding factors. Positive
      post-only results were also evident in a related program designed specifically
      for medical students. The study concludes by specifying a number of implications,
      including potential avenues for the wider dissemination of this program and
      promising directions for future research.

PMID- 29320410
TI  - Advances in Non-Destructive Early Assessment of Fruit Ripeness towards Defining
      Optimal Time of Harvest and Yield Prediction-A Review.
AB  - Global food security for the increasing world population not only requires
      increased sustainable production of food but a significant reduction in pre- and
      post-harvest waste. The timing of when a fruit is harvested is critical for
      reducing waste along the supply chain and increasing fruit quality for consumers.
      The early in-field assessment of fruit ripeness and prediction of the harvest
      date and yield by non-destructive technologies have the potential to
      revolutionize farming practices and enable the consumer to eat the tastiest and
      freshest fruit possible. A variety of non-destructive techniques have been
      applied to estimate the ripeness or maturity but not all of them are applicable
      for in situ (field or glasshouse) assessment. This review focuses on the non
      destructive methods which are promising for, or have already been applied to, the
      pre-harvest in-field measurements including colorimetry, visible imaging,
      spectroscopy and spectroscopic imaging. Machine learning and regression models
      used in assessing ripeness are also discussed.

PMID- 29320408
TI  - Outer Membrane Vesicle Vaccines from Biosafe Surrogates Prevent Acute Lethal
      Glanders in Mice.
AB  - Burkholderia mallei is a host-adapted Gram-negative mammalian pathogen that
      causes the severe disease glanders. Glanders can manifest as a rapid acute
      progression or a chronic debilitating syndrome primarily affecting solipeds and
      humans in close association with infected animals. In USA, B. mallei is
      classified as one of the most important bacterial biothreat agents. Presently,
      there is no licensed glanders vaccine available for humans or animals. In this
      work, outer membrane vesicles (OMVs) were isolated from three attenuated biosafe
      bacterial strains, Burkholderia pseudomallei Bp82, B. thailandensis E555, and B.
      thailandensis TxDOH and used to vaccinate mice. B. thailandensis OMVs induced
      significantly higher antibody responses that were investigated. B. mallei
      specific serum antibody responses were of higher magnitude in mice vaccinated
      with B. thailandensis OMVs compared to levels in mice vaccinated with B.
      pseudomallei OMVs. OMVs derived from biosafe strains protected mice from acute
      lethal glanders with vesicles from the two B. thailandensis strains affording
      significant protection (>90%) up to 35 days post-infection with some up to 60
      days. Organ loads from 35-day survivors indicated bacteria colonization of the
      lungs, liver, and spleen while those from 60 days had high CFUs in the spleens.
      The highest antibody producing vaccine (B. thailandensis E555 OMVs) also
      protected C57BL/6 mice from acute inhalational glanders with evidence of full
      protection.

PMID- 29320411
TI  - Inihibition of Glycolysis by Using a Micro/Nano-Lipid Bromopyruvic Chitosan
      Carrier as a Promising Tool to Improve Treatment of Hepatocellular Carcinoma.
AB  - Glucose consumption in many types of cancer cells, in particular hepatocellular
      carcinoma (HCC), was followed completely by over-expression of type II hexokinase
      (HKII). This evidence has been used in modern pharmacotherapy to discover
      therapeutic target against glycolysis in cancer cells. Bromopyruvate (BrPA)
      exhibits antagonist property against HKII and can be used to inhibit glycolysis.
      However, the clinical application of BrPA is mostly combined with inhibition
      effect for healthy cells particularly erythrocytes. Our strategy is to
      encapsulate BrPA in a selected vehicle, without any leakage of BrPA out of
      vehicle in blood stream. This structure has been constructed from chitosan
      embedded into oleic acid layer and then coated by dual combination of folic acid
      (FA) and bovine serum albumin (BSA). With FA as specific ligand for cancer folate
      receptor and BSA that can be an easy binding for hepatocytes, they can raise the
      potential selection of carrier system.

PMID- 29320414
TI  - A New Localization System for Indoor Service Robots in Low Luminance and Slippery
      Indoor Environment Using Afocal Optical Flow Sensor Based Sensor Fusion.
AB  - In this paper, a new localization system utilizing afocal optical flow sensor
      (AOFS) based sensor fusion for indoor service robots in low luminance and
      slippery environment is proposed, where conventional localization systems do not
      perform well. To accurately estimate the moving distance of a robot in a slippery
      environment, the robot was equipped with an AOFS along with two conventional
      wheel encoders. To estimate the orientation of the robot, we adopted a forward
      viewing mono-camera and a gyroscope. In a very low luminance environment, it is
      hard to conduct conventional feature extraction and matching for localization.
      Instead, the interior space structure from an image and robot orientation was
      assessed. To enhance the appearance of image boundary, rolling guidance filter
      was applied after the histogram equalization. The proposed system was developed
      to be operable on a low-cost processor and implemented on a consumer robot.
      Experiments were conducted in low illumination condition of 0.1 lx and carpeted
      environment. The robot moved for 20 times in a 1.5 * 2.0 m square trajectory.
      When only wheel encoders and a gyroscope were used for robot localization, the
      maximum position error was 10.3 m and the maximum orientation error was 15.4
      degrees . Using the proposed system, the maximum position error and orientation
      error were found as 0.8 m and within 1.0 degrees , respectively.

PMID- 29320412
TI  - Functional Testing of SLC26A4 Variants-Clinical and Molecular Analysis of a
      Cohort with Enlarged Vestibular Aqueduct from Austria.
AB  - The prevalence and spectrum of sequence alterations in the SLC26A4 gene, which
      codes for the anion exchanger pendrin, are population-specific and account for at
      least 50% of cases of non-syndromic hearing loss associated with an enlarged
      vestibular aqueduct. A cohort of nineteen patients from Austria with hearing loss
      and a radiological alteration of the vestibular aqueduct underwent Sanger
      sequencing of SLC26A4 and GJB2, coding for connexin 26. The pathogenicity of
      sequence alterations detected was assessed by determining ion transport and
      molecular features of the corresponding SLC26A4 protein variants. In this group,
      four uncharacterized sequence alterations within the SLC26A4 coding region were
      found. Three of these lead to protein variants with abnormal functional and
      molecular features, while one should be considered with no pathogenic potential.
      Pathogenic SLC26A4 sequence alterations were only found in 12% of patients.
      SLC26A4 sequence alterations commonly found in other Caucasian populations were
      not detected. This survey represents the first study on the prevalence and
      spectrum of SLC26A4 sequence alterations in an Austrian cohort and further
      suggests that genetic testing should always be integrated with functional
      characterization and determination of the molecular features of protein variants
      in order to unequivocally identify or exclude a causal link between genotype and
      phenotype.

PMID- 29320413
TI  - Adherence to the Mediterranean Diet and Inflammatory Markers.
AB  - The aim was to assess inflammatory markers among adults and adolescents in
      relation to the adherence to the Mediterranean diet. A random sample (219 males
      and 379 females) of the Balearic Islands population (12-65 years) was
      anthropometrically measured and provided a blood sample to determine biomarkers
      of inflammation. Dietary habits were assessed and the adherence to the
      Mediterranean dietary pattern calculated. The prevalence of metabolic syndrome
      increased with age in both sexes. The adherence to the Mediterranean diet in
      adolescent males was 51.3% and 45.7% in adults, whereas in females 53.1% and
      44.3%, respectively. In males, higher adherence to the Mediterranean diet was
      associated with higher levels of adiponectin and lower levels of leptin, tumor
      necrosis factor alpha (TNF-alpha), plasminogen activator inhibitor 1 (PAI-1) and
      high-sensitivity C-reactive protein (hs-CRP) in adults, but not in young
      subjects. In females, higher adherence was associated with lower levels of leptin
      in the young group, PAI-1 in adults and hs-CRP in both groups. With increasing
      age in both sexes, metabolic syndrome increases, but the adherence to the
      Mediterranean diet decreases. Low adherence to the Mediterranean dietary pattern
      (MDP) is directly associated with a worse profile of plasmatic inflammation
      markers.

PMID- 29320415
TI  - Heavy Environmental Pressure in Campania and Other Italian Regions: A Short
      Review of Available Evidence.
AB  - The area of Naples and Campania region, in Italy, are experiencing the dramatic
      consequences of diffuse and illegal waste dumping, resulting in possible threats
      to human health. This area has been referred to as the "Land of Fires" because of
      the common practice of waste burning. International interest in the Campania
      "waste emergency" has triggered several epidemiological studies. This article is
      aimed at highlighting the body of evidence available concerning human and
      environmental contamination in the Campania region, and considers the possible
      lack of comparable knowledge about the situation in other areas suffering from
      high environmental pollution. We analyzed the results of studies addressing
      environmental pollution and population health in the Campania region, starting
      from the most recent reviews on this topic, and compared their findings with
      those concerning other regions. We reviewed 18 studies of epidemiological/cancer
      surveillance and human or animal biomonitoring. These studies show worrying
      results, which could be considered comparable to those available for other
      Italian areas impacted by heavy industrial activities. The release of
      environmental contaminants associated with waste incineration and waste disposal
      in landfills poses a risk to public health, as shown by a number of studies
      (although not conclusively). The current knowledge available for the Campania
      region is better than that available for other areas which are facing similar
      problems due to anthropic activities, including illegal waste trafficking. Thus,
      Naples and Campania could represent a valuable setting to develop general models
      for studies of environmental and human contamination.

PMID- 29320417
TI  - Social Support, Religious Endorsement, and Career Commitment: A Study on Saudi
      Nurses.
AB  - The present study investigates the effect of perceived social support (PSS) and
      perceived religious endorsement (PRE) on career commitment (CC) of Saudi nurses.
      The investigation also extends to the moderating role of different demographic
      and organizational factors in the extent of PSS, and career commitment these
      nurses report. Data required for meeting these study objectives were collected
      from male and female Saudi nurses through a structured questionnaire. Multiple
      regressions using Partial Least Squares based Structural Equation Model, Smart
      PLS version 3.0, and independent sample t-test using SPSS version 22.0, were used
      to analyze data. The study findings reveal that both perceived social support and
      perceived religious endorsement are important antecedents of career commitment of
      Saudi nurses. However, private-sector nurses are found to exhibit a significantly
      higher level of career commitment compared to their public-sector counterparts.
      Nurses with greater educational attainment perceive higher level of social
      support and express greater career commitment than their less educated peers.
      These findings suggest that nursing as a profession should be more openly
      discussed in both secular and religious contexts, to ensure an adequate level of
      respect and compassion on behalf of the public. In particular, endorsement from
      the individual nurses' social networks is vital in maintaining their wellbeing
      and career commitment. Given the religious influence in all aspects of life in
      the Saudi society, the current practice of gender-based segregation in Saudi
      hospitals and clinics seems to be meaningful for sustaining the career commitment
      of the nurses.

PMID- 29320416
TI  - Eating Patterns in Patients with Compensated Cirrhosis: A Case-Control Study.
AB  - BACKGROUND: There is growing evidence suggesting that maintaining an adequate
      nutritional status for patients with liver cirrhosis (LC) is relevant to prevent
      complications. The present study aimed to describe dietary behaviours of patients
      with compensated and non-complicated LC and comparing them with those of subjects
      from the general population. METHODS: In this case-control study, patients were
      volunteers enrolled in the ALICIR (ALImentation et CIRrhose) study, an
      observational survey nested in two French prospective cohorts of patients with
      biopsy-proven compensated cirrhosis related either to excessive alcohol
      consumption (CIRRAL) or to hepatitis B or C virus infection (CirVir). Controls
      were selected from the NutriNet-Sante cohort. Dietary data were collected through
      a semi quantitative food frequency questionnaire. Dietary and nutritional data
      were compared using multi-adjusted paired Student's tests. RESULTS: Between June
      2014 and February 2016, 174 patients of CirVir (N = 97) or CIRRAL (N = 77) were
      matched with 348 controls from the NutriNet-Sante cohort, according to gender,
      age, BMI and educational level. Compared to controls, patients (mean +/- SD)
      consumed more sodas (236.0 +/- 29.8 mL vs. 83.0 +/- 33.0 mL) and water (1787.6 +/
      80.6 mL vs. 933.6 +/- 85.3 mL), and lower amounts of salty snacks (4.2 +/- 1.42
      g vs. 9.0 +/- 1.6 g) and alcoholic beverages (71.8 +/- 23.4 g vs. 151.2 +/- 25.9
      g), with all p values < 0.0001. Dietary behaviours differed according to LC
      aetiology. CONCLUSIONS: Dietary behaviour of patients significantly differed from
      subjects from the general population.

PMID- 29320418
TI  - Analysis of an ABE Scheme with Verifiable Outsourced Decryption.
AB  - Attribute-based encryption (ABE) is a popular cryptographic technology to protect
      the security of users' data in cloud computing. In order to reduce its decryption
      cost, outsourcing the decryption of ciphertexts is an available method, which
      enables users to outsource a large number of decryption operations to the cloud
      service provider. To guarantee the correctness of transformed ciphertexts
      computed by the cloud server via the outsourced decryption, it is necessary to
      check the correctness of the outsourced decryption to ensure security for the
      data of users. Recently, Li et al. proposed a full verifiability of the
      outsourced decryption of ABE scheme (ABE-VOD) for the authorized users and
      unauthorized users, which can simultaneously check the correctness of the
      transformed ciphertext for both them. However, in this paper we show that their
      ABE-VOD scheme cannot obtain the results which they had shown, such as finding
      out all invalid ciphertexts, and checking the correctness of the transformed
      ciphertext for the authorized user via checking it for the unauthorized user. We
      first construct some invalid ciphertexts which can pass the validity checking in
      the decryption algorithm. That means their "verify-then-decrypt" skill is
      unavailable. Next, we show that the method to check the validity of the
      outsourced decryption for the authorized users via checking it for the
      unauthorized users is not always correct. That is to say, there exist some
      invalid ciphertexts which can pass the validity checking for the unauthorized
      user, but cannot pass the validity checking for the authorized user.

PMID- 29320420
TI  - Locally Advanced Pancreatic Cancer: A Review of Local Ablative Therapies.
AB  - Pancreatic cancer is typically characterized by its aggressive tumor growth and
      dismal prognosis. Approximately 30% of patients with pancreatic cancer present
      with locally advanced disease, broadly defined as having a tumor-to-artery
      interface >180 degrees , having an unreconstructable portal vein or superior
      mesenteric vein and no signs of metastatic disease. These patients are currently
      designated to palliative systemic chemotherapy, though median overall survival
      remains poor (approximately 11 months). Therefore, several innovative local
      therapies have been investigated as new treatment options for locally advanced
      pancreatic cancer (LAPC). This article provides an overview of available data
      with regard to morbidity and oncological outcome of novel local therapies for
      LAPC.

PMID- 29320422
TI  - Feasibility of Detecting Natural Frequencies of Hydraulic Turbines While in
      Operation, Using Strain Gauges.
AB  - Nowadays, hydropower plays an essential role in the energy market. Due to their
      fast response and regulation capacity, hydraulic turbines operate at off-design
      conditions with a high number of starts and stops. In this situation, dynamic
      loads and stresses over the structure are high, registering some failures over
      time, especially in the runner. Therefore, it is important to know the dynamic
      response of the runner while in operation, i.e., the natural frequencies, damping
      and mode shapes, in order to avoid resonance and fatigue problems. Detecting the
      natural frequencies of hydraulic turbine runners while in operation is
      challenging, because they are inaccessible structures strongly affected by their
      confinement in water. Strain gauges are used to measure the stresses of hydraulic
      turbine runners in operation during commissioning. However, in this paper, the
      feasibility of using them to detect the natural frequencies of hydraulic turbines
      runners while in operation is studied. For this purpose, a large Francis turbine
      runner (444 MW) was instrumented with several strain gauges at different
      positions. First, a complete experimental strain modal testing (SMT) of the
      runner in air was performed using the strain gauges and accelerometers. Then, the
      natural frequencies of the runner were estimated during operation by means of
      analyzing accurately transient events or rough operating conditions.

PMID- 29320421
TI  - Comparative Analysis of Different Platelet Lysates and Platelet Rich Preparations
      to Stimulate Tendon Cell Biology: An In Vitro Study.
AB  - The poor healing potential of tendons is still a clinical problem, and the use of
      Platelet Rich Plasma (PRP) was hypothesized to stimulate healing. As the efficacy
      of PRPs remains unproven, platelet lysate (PL) could be an alternative with its
      main advantages of storage and characterization before use. Five different blood
      products were prepared from 16 male donors: human serum, two PRPs (Arthrex, (PRP
      ACP); RegenLab (PRP-BCT)), platelet concentrate (apheresis, PC), and PL (freezing
      thawing destruction of PC). Additionally, ten commercial allogenic PLs (AlloPL)
      from pooled donors were tested. The highest concentration of most growth factors
      was found in AlloPL, whereas the release of growth factors lasted longer in the
      other products. PRP-ACP, PRP-BCT, and PC significantly increased cell viability
      of human tenocyte-like cells, whereas PC and AlloPL increased Col1A1 expression
      and PRP-BCT increased Col3A1 expression. MMP-1, IL-1beta, and HGF expression was
      significantly increased and Scleraxis expression decreased by most blood
      products. COX1 expression significantly decreased by PC and AlloPL. No clear
      positive effects on tendon cell biology could be shown, which might partially
      explain the weak outcome results in clinical practice. Pooled PL seemed to have
      the most beneficial effects and might be the future in using blood products for
      tendon tissue regeneration.

PMID- 29320423
TI  - New Thiazoline-Tetralin Derivatives and Biological Activity Evaluation.
AB  - In this study, novel N'-(3-cyclohexyl/phenyl-4-(substituted phenyl)thiazole-2(3H)
      ylidene)-2-[(5,6,7,8-tetrahydronaphthalen-2-yl)oxy]acetohydrazide (4a-4k)
      derivatives were synthesized and their anticancer potency were evaluated on human
      breast adenocarcinoma cell line (MCF-7), human lung carcinoma cell line (A549)
      and mouse embryoblast cell line (NIH/3T3) using the MTT method, DNA synthesis
      inhibition and flow cytometric analysis. Compound 4e bearing 4-methoxyphenyl
      moiety exhibited the highest antitumor efficiency against MCF-7 cell line with
      higher DNA synthesis inhibition and apoptotic cell percentages (ealy+late
      apoptotic cell). On the other hand, compounds 4f, 4g, and 4h bearing 4-bromo, 4
      chloro and 4-florophenyl moieties, respectively caused excellent apoptosis levels
      against A549 cell line when treated with lower concentration even than cisplatin.
      Anticholinesterase activity of the compounds were also tested, compound 4h showed
      49.92% inhibition of acetylcholinesterase (AChE).

PMID- 29320424
TI  - A Retrospective Examination of Feline Leukemia Subgroup Characterization: Viral
      Interference Assays to Deep Sequencing.
AB  - Feline leukemia virus (FeLV) was the first feline retrovirus discovered, and is
      associated with multiple fatal disease syndromes in cats, including lymphoma. The
      original research conducted on FeLV employed classical virological techniques. As
      methods have evolved to allow FeLV genetic characterization, investigators have
      continued to unravel the molecular pathology associated with this fascinating
      agent. In this review, we discuss how FeLV classification, transmission, and
      disease-inducing potential have been defined sequentially by viral interference
      assays, Sanger sequencing, PCR, and next-generation sequencing. In particular, we
      highlight the influences of endogenous FeLV and host genetics that represent FeLV
      research opportunities on the near horizon.

PMID- 29320426
TI  - Self-Assembled AgNP-Containing Nanocomposites Constructed by Electrospinning as
      Efficient Dye Photocatalyst Materials for Wastewater Treatment.
AB  - The design and self-assembly of graphene oxide (GO)-based composite membranes
      have attracted enormous attention due to their wide application in nanomaterial
      and environmental fields. In this work, we have successfully developed a strategy
      to fabricate new composite membranes based on poly(vinyl alcohol)/poly(acrylic
      acid)/carboxyl-functionalized graphene oxide modified with silver nanoparticles
      (PVA/PAA/GO-COOH@AgNPs), which were prepared via thermal treatment and the
      electrospinning technique. Due to the strong pi-pi forces and strong
      electrostatic interactions of GO-COOH sheets, the prepared composite membranes
      and their lager surface areas were modified by scores of AgNPs, which
      demonstrated that a high-efficiency photocatalyst removed the organic dyes from
      the aqueous solutions. The prepared PVA/PAA/GO-COOH@AgNPs nanocomposite membranes
      showed a remarkable photocatalytic capacity in the catalytic degradation of the
      methylene blue dye solutions. Most importantly, the whole process was easy, mild,
      and eco-friendly. Additionally, the as-prepared membranes could be repeatedly
      used after the catalytic reaction.

PMID- 29320425
TI  - Targeting Pancreatic Cancer Cell Plasticity: The Latest in Therapeutics.
AB  - Mortality remains alarmingly high for patients diagnosed with pancreatic ductal
      adenocarcinoma (PDAC), with 93% succumbing to the disease within five years. The
      vast majority of PDAC cases are driven by activating mutations in the proto
      oncogene KRAS, which results in constitutive proliferation and survival
      signaling. As efforts to target RAS and its downstream effectors continue,
      parallel research aimed at identifying novel targets is also needed in order to
      improve therapeutic options and efficacy. Recent studies demonstrate that self
      renewing cancer stem cells (CSCs) contribute to metastatic dissemination and
      therapy failure, the causes of mortality from PDAC. Here, we discuss current
      challenges in PDAC therapeutics, highlight the contribution of mesenchymal/CSC
      plasticity to PDAC pathogenesis, and propose that targeting the drivers of
      plasticity will prove beneficial. Increasingly, intrinsic oncogenic and extrinsic
      pro-growth/survival signaling emanating from the tumor microenvironment (TME) are
      being implicated in the de novo generation of CSC and regulation of tumor cell
      plasticity. An improved understanding of key regulators of PDAC plasticity is
      providing new potential avenues for targeting the properties associated with CSC
      (including enhanced invasion and migration, metastatic outgrowth, and resistance
      to therapy). Finally, we describe the growing field of therapeutics directed at
      cancer stem cells and cancer cell plasticity in order to improve the lives of
      patients with PDAC.

PMID- 29320427
TI  - Peptide-Mediated Liposome Fusion: The Effect of Anchor Positioning.
AB  - A minimal model system for membrane fusion, comprising two complementary peptides
      dubbed "E" and "K" joined to a cholesterol anchor via a polyethyleneglycol
      spacer, has previously been developed in our group. This system promotes the
      fusion of large unilamellar vesicles and facilitates liposome-cell fusion both in
      vitro and in vivo. Whilst several aspects of the system have previously been
      investigated to provide an insight as to how fusion is facilitated, anchor
      positioning has not yet been considered. In this study, the effects of placing
      the anchor at either the N-terminus or in the center of the peptide are
      investigated using a combination of circular dichroism spectroscopy, dynamic
      light scattering, and fluorescence assays. It was discovered that anchoring the
      "K" peptide in the center of the sequence had no effect on its structure, its
      ability to interact with membranes, or its ability to promote fusion, whereas
      anchoring the 'E' peptide in the middle of the sequence dramatically decreases
      fusion efficiency. We postulate that anchoring the 'E' peptide in the middle of
      the sequence disrupts its ability to form homodimers with peptides on the same
      membrane, leading to aggregation and content leakage.

PMID- 29320428
TI  - Monitoring Reaction Paths Using Vibrational Spectroscopies: The Case of the
      Dehydrogenation of Propane toward Propylene on Pd-Doped Cu(111) Surface.
AB  - Monitoring reaction paths is not only a fundamental scientific issue but also
      helps us to understand and optimize the catalytic process. Infrared (IR) and
      Raman spectroscopies are powerful tools for detecting particular molecules or
      intermediate products as a result of their ability to provide the molecular
      "finger-print". However, theoretical modeling for the vibrational spectra of
      molecular adsorbates on metallic surfaces is a long-standing challenge, because
      accurate descriptions of the electronic structure for both the metallic
      substrates and adsorbates are required. In the present work, we applied a quasi
      analytical IR and Raman simulation method to monitor the dehydrogenation of
      propane towards propylene on a Pd-doped Cu(111) surface in real-time. Different
      Pd ensembles were used to construct the single-atom catalyst (SAC). We found that
      the number of sublayer Pd atoms could only affect the intensity of the peak
      rather than the peak position on the vibrational spectra. However, with the
      dehydrogenation reaction proceeding, both IR and Raman spectra were changed
      greatly, which indicates that every reaction step can be distinguished from the
      point of view of vibrational spectroscopies. Additionally, we found that the
      catalytic process, which starts from different initial states, shows different
      spectral profiles. The present results suggest that the vibrational
      spectroscopies obtained by the high-precision simulations pave the way for
      identifying different catalytic reaction paths.

PMID- 29320429
TI  - Very High Cycle Fatigue Behavior of a Directionally Solidified Ni-Base Superalloy
      DZ4.
AB  - The effect of casting pores on the very high cycle fatigue (VHCF) behavior of a
      directionally solidified (DS) Ni-base superalloy DZ4 is investigated. Casting and
      hot isostatic pressing (HIP) specimens were subjected to very high cycle fatigue
      loading in an ambient atmosphere. The results demonstrated that the continuously
      descending S-N curves were exhibited for both the casting and HIP specimens. Due
      to the elimination of the casting pores, the HIP samples had better fatigue
      properties than the casting samples. The subsurface crack initiated from the
      casting pore in the casting specimens at low stress amplitudes, whereas fatigue
      crack initiated from crystallographic facet decohesion for the HIP specimens.
      When considering the casting pores as initial cracks, there exists a critical
      stress intensity threshold ranged from 1.1 to 1.3 MPa m , below which fatigue
      cracks may not initiate from the casting pores. Furthermore, the effect of the
      casting pores on the fatigue limit is estimated based on a modified El Haddad
      model, which is in good agreement with the experimental results. Fatigue life for
      both the casting and HIP specimens is well predicted using the Fatigue Indicator
      Parameter (FIP) model.

PMID- 29320430
TI  - Compatibility between Co-Metallized PbTe Thermoelectric Legs and an Ag-Cu-In
      Brazing Alloy.
AB  - In thermoelectric (TE) generators, maximizing the efficiency of conversion of
      direct heat to electricity requires the reduction of any thermal and electrical
      contact resistances between the TE legs and the metallic contacts. This
      requirement is especially challenging in the development of intermediate to high
      temperature TE generators. PbTe-based TE materials are known to be highly
      efficient up to temperatures of around 500  degrees C; however, only a few
      practical TE generators based on these materials are currently commercially
      available. One reason for that is the insufficient bonding techniques between the
      TE legs and the hot-side metallic contacts. The current research is focused on
      the interaction between cobalt-metallized n-type 9.104 * 10-3 mol % PbI2-doped
      PbTe TE legs and the Ag0.32Cu0.43In0.25 brazing alloy, which is free of volatile
      species. Clear and fine interfaces without any noticeable formation of adverse
      brittle intermetallic compounds were observed following prolonged thermal
      treatment testing. Moreover, a reasonable electrical contact resistance of ~2.25
      mOmegamm2 was observed upon brazing at 600  degrees C, highlighting the potential
      of such contacts while developing practical PbTe-based TE generators.

PMID- 29320434
TI  - Small Imaging Depth LIDAR and DCNN-Based Localization for Automated Guided
      Vehicle.
AB  - We present our third prototype sensor and a localization method for Automated
      Guided Vehicles (AGVs), for which small imaging LIght Detection and Ranging
      (LIDAR) and fusion-based localization are fundamentally important. Our small
      imaging LIDAR, named the Single-Photon Avalanche Diode (SPAD) LIDAR, uses a time
      of-flight method and SPAD arrays. A SPAD is a highly sensitive photodetector
      capable of detecting at the single-photon level, and the SPAD LIDAR has two SPAD
      arrays on the same chip for detection of laser light and environmental light.
      Therefore, the SPAD LIDAR simultaneously outputs range image data and monocular
      image data with the same coordinate system and does not require external
      calibration among outputs. As AGVs travel both indoors and outdoors with
      vibration, this calibration-less structure is particularly useful for AGV
      applications. We also introduce a fusion-based localization method, named SPAD
      DCNN, which uses the SPAD LIDAR and employs a Deep Convolutional Neural Network
      (DCNN). SPAD DCNN can fuse the outputs of the SPAD LIDAR: range image data,
      monocular image data and peak intensity image data. The SPAD DCNN has two
      outputs: the regression result of the position of the SPAD LIDAR and the
      classification result of the existence of a target to be approached. Our third
      prototype sensor and the localization method are evaluated in an indoor
      environment by assuming various AGV trajectories. The results show that the
      sensor and localization method improve the localization accuracy.

PMID- 29320432
TI  - Validity of Predictive Equations for Resting Energy Expenditure Developed for
      Obese Patients: Impact of Body Composition Method.
AB  - Predictive equations have been specifically developed for obese patients to
      estimate resting energy expenditure (REE). Body composition (BC) assessment is
      needed for some of these equations. We assessed the impact of BC methods on the
      accuracy of specific predictive equations developed in obese patients. REE was
      measured (mREE) by indirect calorimetry and BC assessed by bioelectrical
      impedance analysis (BIA) and dual-energy X-ray absorptiometry (DXA). mREE,
      percentages of prediction accuracy (+/-10% of mREE) were compared. Predictive
      equations were studied in 2588 obese patients. Mean mREE was 1788 +/- 6.3 kcal/24
      h. Only the Muller (BIA) and Harris & Benedict (HB) equations provided REE with
      no difference from mREE. The Huang, Muller, Horie-Waitzberg, and HB formulas
      provided a higher accurate prediction (>60% of cases). The use of BIA provided
      better predictions of REE than DXA for the Huang and Muller equations. Inversely,
      the Horie-Waitzberg and Lazzer formulas provided a higher accuracy using DXA.
      Accuracy decreased when applied to patients with BMI >= 40, except for the Horie
      Waitzberg and Lazzer (DXA) formulas. Muller equations based on BIA provided a
      marked improvement of REE prediction accuracy than equations not based on BC. The
      interest of BC to improve REE predictive equations accuracy in obese patients
      should be confirmed.

PMID- 29320431
TI  - Galectin Targeted Therapy in Oncology: Current Knowledge and Perspectives.
AB  - The incidence and mortality of cancer have increased over the past decades.
      Significant progress has been made in understanding the underpinnings of this
      disease and developing therapies. Despite this, cancer still remains a major
      therapeutic challenge. Current therapeutic research has targeted several aspects
      of the disease such as cancer development, growth, angiogenesis and metastases.
      Many molecular and cellular mechanisms remain unknown and current therapies have
      so far failed to meet their intended potential. Recent studies show that glycans,
      especially oligosaccharide chains, may play a role in carcinogenesis as
      recognition patterns for galectins. Galectins are members of the lectin family,
      which show high affinity for beta-galactosides. The galectin-glycan conjugate
      plays a fundamental role in metastasis, angiogenesis, tumor immunity,
      proliferation and apoptosis. Galectins' action is mediated by a structure
      containing at least one carbohydrate recognition domain (CRD). The potential
      prognostic value of galectins has been described in several neoplasms and helps
      clinicians predict disease outcome and determine therapeutic interventions.
      Currently, new therapeutic strategies involve the use of inhibitors such as
      competitive carbohydrates, small non-carbohydrate binding molecules and
      antibodies. This review outlines our current knowledge regarding the mechanism of
      action and potential therapy implications of galectins in cancer.

PMID- 29320435
TI  - Updated Overview of Infrared Spectroscopy Methods for Detecting Mycotoxins on
      Cereals (Corn, Wheat, and Barley).
AB  - Each year, mycotoxins cause economic losses of several billion US dollars
      worldwide. Consequently, methods must be developed, for producers and cereal
      manufacturers, to detect these toxins and to comply with regulations.
      Chromatographic reference methods are time consuming and costly. Thus,
      alternative methods such as infrared spectroscopy are being increasingly
      developed to provide simple, rapid, and nondestructive methods to detect
      mycotoxins. This article reviews research conducted over the last eight years
      into the use of near-infrared and mid-infrared spectroscopy to monitor mycotoxins
      in corn, wheat, and barley. More specifically, we focus on the Fusarium species
      and on the main fusariotoxins of deoxynivalenol, zearalenone, and fumonisin B1
      and B2. Quantification models are insufficiently precise to satisfy the legal
      requirements. Sorting models with cutoff levels are the most promising
      applications.

PMID- 29320433
TI  - Benefits of Fish Oil Consumption over Other Sources of Lipids on Metabolic
      Parameters in Obese Rats.
AB  - This study evaluated the effect of the consumption of different levels and
      sources of lipids on metabolic parameters of Wistar rats. Animals were fed with
      high-fat diet (HFD) containing 20% of lard for 12 weeks to cause metabolic
      obesity. Subsequently, the animals were divided into six groups and were fed
      diets with lipid concentrations of 5% or 20% of lard (LD), soybean oil (SO) or
      fish oil (FO), for 4 weeks. Data were submitted to analysis of variance (two-way)
      followed by Tukey post hoc test (p < 0.05). The groups that consumed FO showed
      less weight gain and lower serum levels of triacylglycerol (TAG), total
      cholesterol and fractions, aspartate aminotransferase (AST) activity, atherogenic
      index, less amount of fat in the carcass, decreased Lee index and lower total
      leukocyte counting (p < 0.05). These same parameters were higher in LD treatment
      (p < 0.05). In the concentration of 20%, carcass fat content, blood glucose
      levels, as well as alanine aminotransferase (ALT) and gamma glutamyl transferase
      (GGT) decreased in FO groups (p < 0.05). The SO group had intermediate results
      regarding the other two treatments (FO and LD). We concluded that fish oil intake
      was able to modulate positively the metabolic changes resulting from HFD.

PMID- 29320436
TI  - The Feasibility and Usability of RunningCoach: A Remote Coaching System for Long
      Distance Runners.
AB  - Studies have shown that about half of the injuries sustained during long-distance
      running involve the knee. Cadence (steps per minute) has been identified as a
      factor that is strongly associated with these running-related injuries, making it
      a worthwhile candidate for further study. As such, it is critical for long
      distance runners to minimize their risk of injury by running at an appropriate
      running cadence. In this paper, we present the results of a study on the
      feasibility and usability of RunningCoach, a mobile health (mHealth) system that
      remotely monitors running cadence levels of runners in a continuous fashion,
      among other variables, and provides immediate feedback to runners in an effort to
      help them optimize their running cadence.

PMID- 29320437
TI  - Is Hypovitaminosis D Related to Incidence of Type 2 Diabetes and High Fasting
      Glucose Level in Healthy Subjects: A Systematic Review and Meta-Analysis of
      Observational Studies.
AB  - There is evidence that vitamin D status is associated with type 2 diabetes. Many
      observational studies have been performed investigating the relationship of
      vitamin D status and circulating biomarkers of glycemic regulation. To find out
      whether this association holds, we conducted a systematic review and meta
      analysis of cross sectional and longitudinal studies. We searched Pubmed, Medline
      and Embase, all through June 2017. The studies were selected to determine the
      effect of vitamin D on the parameters of glucose metabolism in diabetic and non
      diabetic subjects. Correlation coefficients from all studies were pooled in a
      random effects meta-analysis. The risk of bias was assessed using Grading of
      Recommendations Assessment, Development and Evaluation (GRADE) system. We found
      significant inverse relationship of vitamin D status with glycemic level in both
      diabetic (r = -0.223, 95% CI = -0.184 to -0.261, p = 0.000) and non-diabetic (r =
      -0.073, 95% CI = -0.052 to -0.093, p = 0.000) subjects. This meta-analysis
      concludes that hypovitaminosis D is associated with increased risk of
      hyperglycemia both in diabetic and non-diabetic subjects. A future strategy for
      the prevention of impaired glycemic regulation could be individualized
      supplementation of vitamin D.

PMID- 29320438
TI  - Modeling Unobserved Heterogeneity in Susceptibility to Ambient Benzo[a]pyrene
      Concentration among Children with Allergic Asthma Using an Unsupervised Learning
      Algorithm.
AB  - Current studies of gene * air pollution interaction typically seek to identify
      unknown heritability of common complex illnesses arising from variability in the
      host's susceptibility to environmental pollutants of interest. Accordingly, a
      single component generalized linear models are often used to model the risk posed
      by an environmental exposure variable of interest in relation to a priori
      determined DNA variants. However, reducing the phenotypic heterogeneity may
      further optimize such approach, primarily represented by the modeled DNA
      variants. Here, we reduce phenotypic heterogeneity of asthma severity, and also
      identify single nucleotide polymorphisms (SNP) associated with phenotype
      subgroups. Specifically, we first apply an unsupervised learning algorithm method
      and a non-parametric regression to find a biclustering structure of children
      according to their allergy and asthma severity. We then identify a set of SNPs
      most closely correlated with each sub-group. We subsequently fit a logistic
      regression model for each group against the healthy controls using benzo[a]pyrene
      (B[a]P) as a representative airborne carcinogen. Application of such approach in
      a case-control data set shows that SNP clustering may help to partly explain
      heterogeneity in children's asthma susceptibility in relation to ambient B[a]P
      concentration with greater efficiency.

PMID- 29320441
TI  - RESTOP: Retaining External Peripheral State in Intermittently-Powered Sensor
      Systems.
AB  - Energy harvesting sensor systems typically incorporate energy buffers (e.g.,
      rechargeable batteries and supercapacitors) to accommodate fluctuations in
      supply. However, the presence of these elements limits the miniaturization of
      devices. In recent years, researchers have proposed a new paradigm, transient
      computing, where systems operate directly from the energy harvesting source and
      allow computation to span across power cycles, without adding energy buffers.
      Various transient computing approaches have addressed the challenge of power
      intermittency by retaining the processor's state using non-volatile memory.
      However, no generic approach has yet been proposed to retain the state of
      peripherals external to the processing element. This paper proposes RESTOP,
      flexible middleware which retains the state of multiple external peripherals that
      are connected to a computing element (i.e., a microcontroller) through protocols
      such as SPI or I 2 C. RESTOP acts as an interface between the main application
      and the peripheral, which keeps a record, at run-time, of the transmitted data in
      order to restore peripheral configuration after a power interruption. RESTOP is
      practically implemented and validated using three digitally interfaced
      peripherals, successfully restoring their configuration after power
      interruptions, imposing a maximum time overhead of 15% when configuring a
      peripheral. However, this represents an overhead of only 0.82% during complete
      execution of our typical sensing application, which is substantially lower than
      existing approaches.

PMID- 29320439
TI  - Semisynthesis and Biological Evaluation of Oleanolic Acid 3-O-beta-d
      Glucuronopyranoside Derivatives for Protecting H9c2 Cardiomyoblasts against H2O2
      Induced Injury.
AB  - A series of novel oleanolic acid 3-O-beta-d-glucuronopyranoside derivatives have
      been designed and synthesized. Biological evaluation has indicated that some of
      the synthesized compounds exhibit moderate to good activity against H2O2-induced
      injury in rat myocardial cells (H9c2). Particularly, derivative 28-N-isobutyl
      ursolic amide 3-O-beta-d-galactopyranoside (8a) exhibited a greater protective
      effect than the positive control oleanolic acid 3-O-beta-d-glucuronopyranoside,
      indicating that it possesses a great potential for further development as a
      cardiovascular disease modulator by structural modification.

PMID- 29320442
TI  - Optimization of Fermentation Conditions and Bench-Scale for Improvement of a
      Novel Glycoprotein GP-1 Production by Streptomyces kanasenisi ZX01.
AB  - GP-1 is a novel glycoprotein produced by Streptomyces kanasenisi ZX01 that was
      isolated from soil near Kanas Lake with significant bioactivity against tobacco
      mosaic virus. However, extremely low fermentation production has largely hindered
      further research and market applications on glycoprotein GP-1. In this study,
      response surface methodology was used to optimize fermentation conditions in a
      shake flask for higher glycoprotein GP-1 production. When the optimized
      fermentation conditions were inoculum volume of 6%, initial pH of 6.5, and
      rotating speed of 150 rpm, glycoprotein GP-1 production could reach 0.9253 mg/L,
      which was increased by 52.14% compared to the original conditions. In addition,
      scale-up fermentation was conducted in a 5-L bioreactor to preliminarily explore
      the feasibility for mass production of glycoprotein GP-1 in a large fermentor,
      obtaining GP-1 production of 2.54 mg/L under the same conditions, which was 2.75
      times higher than the production obtained from a shake flask of 0.9253 mg/L. This
      work will be helpful to improve GP-1 production on a large scale and lay the
      foundations for developing it as a novel agent against plant virus.

PMID- 29320443
TI  - Evaluation of Asphalt Mixture Low-Temperature Performance in Bending Beam Creep
      Test.
AB  - Low-temperature cracking is one of the most common road pavement distress types
      in Poland. While bitumen performance can be evaluated in detail using bending
      beam rheometer (BBR) or dynamic shear rheometer (DSR) tests, none of the
      normalized test methods gives a comprehensive representation of low-temperature
      performance of the asphalt mixtures. This article presents the Bending Beam Creep
      test performed at temperatures from -20  degrees C to +10  degrees C in order to
      evaluate the low-temperature performance of asphalt mixtures. Both validation of
      the method and its utilization for the assessment of eight types of wearing
      courses commonly used in Poland were described. The performed test indicated that
      the source of bitumen and its production process (and not necessarily only
      bitumen penetration) had a significant impact on the low-temperature performance
      of the asphalt mixtures, comparable to the impact of binder modification (neat,
      polymer-modified, highly modified) and the aggregate skeleton used in the mixture
      (Stone Mastic Asphalt (SMA) vs. Asphalt Concrete (AC)). Obtained Bending Beam
      Creep test results were compared with the BBR bitumen test. Regression analysis
      confirmed that performing solely bitumen tests is insufficient for comprehensive
      low-temperature performance analysis.

PMID- 29320444
TI  - Preliminary Analyses Showed Short-Term Mental Health Improvements after a Single
      Day Manager Training.
AB  - Psychosocial working conditions attract more and more attention when it comes to
      mental health in the workplace. Trying to support managers to deal with their own
      as well as their employees' psychological risk factors, we conducted a specific
      manager training. Within this investigation, we wanted to learn about the
      training's effects and acceptance. A single-day manager training was provided in
      a large industrial company in Germany. The participants were asked to fill out
      questionnaires regarding their own physical and mental health condition as well
      as their working situation. Questionnaires were distributed at baseline, 3-month,
      and 12-month follow-up. At this point of time the investigation is still ongoing.
      The current article focuses on short-term preliminary effects. Analyses only
      included participants that already completed baseline and three months follow-up.
      Preliminary results from three-month follow-up survey (n = 33, nmale = 30, Mage =
      47.5) indicated positive changes in the manager's mental health condition
      measured by the Patient Health Questionnaire for depression (PHQ-9: Mt1 = 3.82,
      Mt2 = 3.15). Training managers about common mental disorders and risk factors at
      the workplace within a single-day workshop seems to promote positive effects on
      their own mental health. Especially working with the managers on their own early
      stress symptoms might have been an important element.

PMID- 29320445
TI  - Chlorophyll-Inspired Red-Region Fluorophores: Building Block Synthesis and
      Studies in Aqueous Media.
AB  - Fluorophores that absorb and emit in the red spectral region (600-700 nm) are of
      great interest in photochemistry and photomedicine. Eight new target chlorins
      (and 19 new chlorins altogether)-analogues of chlorophyll-of different polarities
      have been designed and synthesized for various applications; seven of the
      chlorins are equipped with a bioconjugatable tether. Hydrophobic or amphiphilic
      chlorins in a non-polar organic solvent (toluene), polar organic solvent (DMF),
      and aqueous or aqueous micellar media show a sharp emission band in the red
      region and modest fluorescence quantum yield (Phif = 0.2-0.3). A Poisson analysis
      implies most micelles are empty and few contain >1 chlorin. Water-soluble
      chlorins each bearing three PEG (oligoethyleneglycol) groups exhibit narrow
      emission bands (full-width-at-half maximum <25 nm). The lifetime of the lowest
      singlet excited state and the corresponding yields and rate constants for
      depopulation pathways (fluorescence, intersystem crossing, internal conversion)
      are generally little affected by the PEG groups or dissolution in aqueous or
      organic media. A set of chlorin-avidin conjugates revealed a 2-fold increase in
      Phif with increased average chlorin/avidin ratio (2.3-12). In summary, the
      chlorins of various polarities described herein are well suited as red-emitting
      fluorophores for applications in aqueous or organic media.

PMID- 29320446
TI  - Physical Activity, Physical Fitness, Body Composition, and Nutrition Are
      Associated with Bone Status in University Students.
AB  - Understanding the modifiable factors that improve and maximize peak bone mass at
      an early age is necessary to design more effective intervention programs to
      prevent osteoporosis. To identify these modifiable factors, we analyzed the
      relationship of physical activity (PA), physical fitness, body composition, and
      dietary intake with bone stiffness index (SI), measured by quantitative
      ultrasonometry in young university students (18-21 years). Moderate-to-vigorous
      PA (MVPA) was the strongest predictor of SI (beta = 0.184; p = 0.035). SI was
      most closely related with very vigorous PA in males (beta = 0.288; p = 0.040) and
      with the number of steps/day in females (beta = 0.319; p = 0.002). An association
      between thigh muscle and SI was consistent in both sexes (beta = 0.328; p <
      0.001). Additionally, extension maximal force was a bone SI predictor factor in
      females (beta = 0.263; p = 0.016) independent of thigh muscle perimeter. Calcium
      intake was the only nutrition parameter that had a positive relationship with SI
      (R = 0.217; p = 0.022). However, it was not included as a predictor for SI in our
      regression models. This study identifies predictors of bone status in each sex
      and indicates that muscle and bone interrelate with PA and fitness in young
      adults.

PMID- 29320447
TI  - Parents' Perspectives on Family Sexuality Communication from Middle School to
      High School.
AB  - Parents' conversations with teens about sex and relationships can play a critical
      role in improving teenage reproductive health by reducing teens' risky sexual
      behavior. However, little is known about how teen-parent communication changes
      from early to middle adolescence and how parents can tailor their communication
      to address their teens' changing development and experiences during these
      periods. In this longitudinal qualitative study, U.S. parents (N = 23)
      participated in interviews when their teens were in early adolescence, then again
      when the teens were in middle adolescence. Participants were largely mothers and
      were from diverse racial/ethnic and educational backgrounds. Thematic analysis
      was used to assess continuity and change in parents' perceptions of teen-parent
      communication. Findings showed that many parents adapted their conversations with
      their teens about sex and relationships as teens developed. Once teens had
      entered high school, more parents described feeling comfortable with their
      conversations. However, parents also more often reported that their teens
      responded negatively to the communication in high school than they had in middle
      school. These findings may help parents to anticipate their own as well as their
      teens' responses to family conversations about sex at different developmental
      time points and to strategize how to effectively talk with their teens about sex
      and relationships to improve their teens' overall reproductive health.

PMID- 29320449
TI  - Changing Trends in Nutritional Behavior among University Students in Greece,
      between 2006 and 2016.
AB  - The objective of the present survey was to study the dietary behavior of
      university students residing away from the family home. In this context, we (a)
      compared their dietary habits in two time periods, namely 2006 and 2016; and (b)
      explored the possible impact of gender on the behavioral changes in nutritional
      choices. A total of four hundred and five university students (2006, n = 242;
      2016, n = 163) participated in the study. Dietary assessment was carried out
      using a qualitative Food Frequency Questionnaire, while data about demographic
      and lifestyle factors were also collected. Students' dietary habits have been
      modified in a generally desirable direction, as reflected, e.g., in the elevated
      consumption of several plant-based foods. Gender was also significantly
      associated with Body Mass Index (BMI) and changes in dietary attitudes. Possible
      reasons for the transition towards healthier and more balanced dietary habits
      could involve the budgetary constraints facing Greece in the last decade, as well
      as increasing nutritional awareness and other socio-cultural factors
      characterizing this target group. A deeper understanding of these relations would
      be crucial to foster nutritional education and further enhance the effectiveness
      of health promotion campaigns.

PMID- 29320450
TI  - Nitrogen Nutrition of Fruit Trees to Reconcile Productivity and Environmental
      Concerns.
AB  - Although perennial fruit crops represent 1% of global agricultural land, they are
      of a great economic importance in world trade and in the economy of many regions.
      The perennial woody nature of fruit trees, their physiological stages of growth,
      the root distribution pattern, and the presence of herbaceous vegetation in
      alleys make orchard systems efficient in the use and recycling of nitrogen (N).
      The present paper intends to review the existing literature on N nutrition of
      young and mature deciduous and evergreen fruit trees with special emphasis to
      temperate and Mediterranean climates. There are two major sources of N
      contributing to vegetative tree growth and reproduction: root N uptake and
      internal N cycling. Optimisation of the use of external and internal N sources is
      important for a sustainable fruit production, as N use efficiency by young and
      mature fruit trees is generally lower than 55% and losses of fertilizer N may
      occur with the consequent economic and environmental concern. Organic
      alternatives to mineral N fertilizer like the application of manure, compost,
      mulching, and cover crops are scarcely used in perennial fruit trees, in spite of
      the fact that society's expectations call for more sustainable production
      techniques and the demand for organic fruits is increasing.

PMID- 29320452
TI  - Structural and Evolutionary Relationships in the Giant Sex Chromosomes of Three
      Microtus Species.
AB  - The genus Microtus has high karyotypic diversity. The existence of notable
      differences in the length of its sex chromosomes contributes to this variation.
      Variations in size are attributed to the enlargement of their heterochromatin
      content, which is of such magnitude in some species that they are referred to as
      "giant sex chromosomes". Here, we perform an intra- and interspecific analysis of
      the molecular composition of the heterochromatic blocks in three species with
      giant sex chromosomes (Microtus chrotorrhinus, M. cabrerae and M. agrestis). Our
      results show that the heterochromatic content is very similar in both the X and Y
      chromosomes of M. chrotorrhinus, and that their molecular composition is more
      closely related to the heterochromatic blocks of M. agrestis than to the sex
      heterochromatin of M. cabrerae; however, species-specific differences do clearly
      exist. Interestingly, the euchromatic regions of the X chromosome of all three of
      these species share a homologous region composed of heterochromatic-related
      sequences. Our results therefore reinforce the idea that certain similarities in
      the original organization of these X chromosomes could have facilitated their
      later enlargement.

PMID- 29320453
TI  - Radar HRRP Target Recognition Based on Stacked Autoencoder and Extreme Learning
      Machine.
AB  - A novel radar high-resolution range profile (HRRP) target recognition method
      based on a stacked autoencoder (SAE) and extreme learning machine (ELM) is
      presented in this paper. As a key component of deep structure, the SAE does not
      only learn features by making use of data, it also obtains feature expressions at
      different levels of data. However, with the deep structure, it is hard to achieve
      good generalization performance with a fast learning speed. ELM, as a new
      learning algorithm for single hidden layer feedforward neural networks (SLFNs),
      has attracted great interest from various fields for its fast learning speed and
      good generalization performance. However, ELM needs more hidden nodes than
      conventional tuning-based learning algorithms due to the random set of input
      weights and hidden biases. In addition, the existing ELM methods cannot utilize
      the class information of targets well. To solve this problem, a regularized ELM
      method based on the class information of the target is proposed. In this paper,
      SAE and the regularized ELM are combined to make full use of their advantages and
      make up for each of their shortcomings. The effectiveness of the proposed method
      is demonstrated by experiments with measured radar HRRP data. The experimental
      results show that the proposed method can achieve good performance in the two
      aspects of real-time and accuracy, especially when only a few training samples
      are available.

PMID- 29320454
TI  - Combined Layer/Particle Approaches in Surface Molecular Imprinting of Proteins:
      Signal Enhancement and Competition.
AB  - Herein we report novel approaches to the molecular imprinting of proteins
      utilizing templates sizing around 10 nm and some 100 nm. The first step comprised
      synthesizing nanoparticles of molecularly imprinted polymers (MIP) towards bovine
      serum albumin (BSA) and characterizing them according to size and binding
      capacity. In a second step, they were utilized as templates. Quartz crystal
      microbalances (QCM) coated with MIP thin films based on BSA MIP nanoparticles
      lead to a two-fold increase in sensor responses, compared with the case of
      directly using the protein as the template. This also established that individual
      BSA molecules exhibit different "epitopes" for molecular imprinting on their
      outer surfaces. In light of this knowledge, a possible MIP-based biomimetic assay
      format was tested by exposing QCM coated with BSA MIP thin films to mixtures of
      BSA and imprinted and non-imprinted polymer (NIP) nanoparticles. At high protein
      concentrations (1000 ppm) measurements revealed aggregation behavior, i.e., BSA
      binding MIP NP onto the MIP surface. This increased sensor responses by more than
      30% during proof of concept measurements. At lower a BSA concentration (500 ppm),
      thin films and particles revealed competitive behavior.

PMID- 29320451
TI  - The Pathogenesis of Staphylococcus aureus Eye Infections.
AB  - Staphylococcus aureus is a major pathogen of the eye able to infect the tear
      duct, eyelid, conjunctiva, cornea, anterior and posterior chambers, and the
      vitreous chamber. Of these infections, those involving the cornea (keratitis) or
      the inner chambers of the eye (endophthalmitis) are the most threatening because
      of their potential to cause a loss in visual acuity or even blindness. Each of
      these ocular sites is protected by the constitutive expression of a variety of
      antimicrobial factors and these defenses are augmented by a protective host
      response to the organism. Such infections often involve a predisposing factor
      that weakens the defenses, such as the use of contact lenses prior to the
      development of bacterial keratitis or, for endophthalmitis, the trauma caused by
      cataract surgery or intravitreal injection. The structural carbohydrates of the
      bacterial surface induce an inflammatory response able to reduce the bacterial
      load, but contribute to the tissue damage. A variety of bacterial secreted
      proteins including alpha-toxin, beta-toxin, gamma-toxin, Panton-Valentine
      leukocidin and other two-component leukocidins mediate tissue damage and
      contribute to the induction of the inflammatory response. Quantitative animal
      models of keratitis and endophthalmitis have provided insights into the S. aureus
      virulence and host factors active in limiting such infections.

PMID- 29320455
TI  - Magnetization Reversal Modes in Short Nanotubes with Chiral Vortex Domain Walls.
AB  - Micromagnetic simulations of magnetization reversal were performed for magnetic
      nanotubes of a finite length, L, equal to 1 and 2 MUm, 50 and 100 nm radii, R,
      and uniaxial anisotropy with "easy axis" parallel to the tube length. I.e., we
      considered relatively short nanotubes with the aspect ratio L/R in the range 10
      40. The non-uniform curling magnetization states on both ends of the nanotubes
      can be treated as vortex domain walls (DW). The domain wall length, Lc, depends
      on the tube geometric parameters and the anisotropy constant Ku, and determines
      the magnetization reversal mode, as well as the switching field value. For
      nanotubes with relative small values of Lc (Lc/L < 0.2) the magnetization
      reversal process is characterized by flipping of the magnetization in the middle
      uniform state. Whereas, for relative large values of Lc, in the reverse magnetic
      field, coupling of two vortex domain walls with opposite magnetization rotation
      directions results in the formation of a specific narrow Neel type DW in the
      middle of the nanotube. The nanotube magnetization suddenly aligns to the applied
      field at the switching field, collapsing the central DW.

PMID- 29320456
TI  - Preparative Purification of Polyphenols from Aronia melanocarpa (Chokeberry) with
      Cellular Antioxidant and Antiproliferative Activity.
AB  - The aim of this study was the purification process of polyphenols from Aronia
      melanocarpa (chokeberry), and the purification parameters were optimised by
      adsorption and desorption tests. By comparing adsorption and desorption ability
      of polyphenols from chokeberry on six kinds of macroporous resin, XAD-7 resin was
      selected. Experiments prove that the best purification parameters of static
      adsorption and desorption were sample pH = 4.0 with 4 h of adsorption; and
      desorption solvent is 95% ethanol (pH = 7.0) with 2 h of desorption. The best
      dynamic parameters were 9.3 bed volume (BV) of sample loading amount at a feeding
      flow rate of 2 BV/h, and washing the column with 5.8 BV of water, followed by
      subsequent elution with an eluent volume of 5.0 mL at an elution flow rate of 2
      BV/h. Next the antioxidant and antiproliferative activity of polyphenols from
      chokeberry, blueberries, haskap berries was studied on HepG2 human liver cancer
      cells. The results show that polyphenol from chokeberry has a strong antioxidant
      effect. Taking into account the content of polyphenols in fruit, polyphenols from
      chokeberry represent a very valuable natural antioxidant source with
      antiproliferative products.

PMID- 29320457
TI  - Evaluating the Joint Toxicity of Two Benzophenone-Type UV Filters on the Green
      Alga Chlamydomonas reinhardtii with Response Surface Methodology.
AB  - The widespread occurrence of benzophenone-type ultraviolet (UV) filter has raised
      the public concerns over the ecotoxicological effects of these chemicals. The
      present study assessed the joint toxicity of two representative benzophenones,
      benzophenone-1 (BP-1) and benzophenone-3 (BP-3), on the green alga Chlamydomonas
      reinhardtii using response surface methodologies (RSM). Specific growth rate and
      photosynthetic pigments were used as endpoints to evaluate the toxic effects.
      Generally, exposure to the combined BP-1 and BP-3 negatively affected cell growth
      and pigments production, with higher inhibitions at higher exposure
      concentrations. The simultaneous reduction in growth rate and pigments contents
      indicated that BP-1 and BP-3 regulated the growth of the tested alga by affecting
      the photosynthesis process. Results also showed that second order polynomial
      regression models fitted well with experimental results for all endpoints. The
      obtained regression models further indicated that the effects of the combination
      stemmed significantly from the linear concentration of BP-1 and BP-3. The overall
      results demonstrated that RSM could be a useful tool in ecotoxicological studies.

PMID- 29320458
TI  - Community Characteristics and Leaf Stoichiometric Traits of Desert Ecosystems
      Regulated by Precipitation and Soil in an Arid Area of China.
AB  - Precipitation is a key environmental factor determining plant community structure
      and function. Knowledge of how community characteristics and leaf stoichiometric
      traits respond to variation in precipitation is crucial for assessing the effects
      of global changes on terrestrial ecosystems. In this study, we measured community
      characteristics, leaf stoichiometric traits, and soil properties along a
      precipitation gradient (35-209 mm) in a desert ecosystem of Northwest China to
      explore the drivers of these factors. With increasing precipitation, species
      richness, aboveground biomass, community coverage, foliage projective cover
      (FPC), and leaf area index (LAI) all significantly increased, while community
      height decreased. The hyperarid desert plants were characterized by lower leaf
      carbon (C) and nitrogen/phosphorus (N/P) levels, and stable N and P, and these
      parameters did not change significantly with precipitation. The growth of desert
      plants was limited more by N than P. Soil properties, rather than precipitation,
      were the main drivers of desert plant leaf stoichiometric traits, whereas
      precipitation made the biggest contribution to vegetation structure and function.
      These results test the importance of precipitation in regulating plant community
      structure and composition together with soil properties, and provide further
      insights into the adaptive strategy of communities at regional scale in response
      to global climate change.

PMID- 29320460
TI  - Fatigue Reliability Assessment for Orthotropic Steel Decks Based on Long-Term
      Strain Monitoring.
AB  - A time-dependent fatigue reliability assessment approach is proposed for welded
      details of orthotropic steel decks (OSDs) using long-term strain monitoring data.
      The fatigue reliability limit function of the welded details is established based
      on the Eurocode specifications. Depending on the distribution characteristics of
      the measured daily equivalent stress range, either the lognormal distribution or
      Gaussian mixture model (GMM) is selected to quantify its uncertainty.
      Subsequently, the fatigue reliability can be calculated using either an explicit
      formula or the Monte Carlo method. This proposed approach is applied for the
      fatigue reliability evaluation of two rib-to-deck and two rib-to-rib welded
      fatigue details of an in-service suspension bridge. The results show that the
      reliability indices decrease significantly with bridge's service life. Except for
      a rib-to-deck detail, all other three welded details cannot meet the target
      fatigue reliability during this bridge's 100-year service life. The proposed
      approach can help bridge owners and operators make informed decisions regarding
      maintenance and repair of potential fatigue cracks.

PMID- 29320459
TI  - The Landscape of Small Non-Coding RNAs in Triple-Negative Breast Cancer.
AB  - Triple-negative breast cancer (TNBC) is an operational term for breast cancers
      lacking targetable estrogen receptor expression and HER2 amplifications. TNBC is,
      therefore, inherently heterogeneous, and is associated with worse prognosis,
      greater rates of metastasis, and earlier onset. TNBC displays mutational and
      transcriptional diversity, and distinct mRNA transcriptional subtypes exhibiting
      unique biology. High-throughput sequencing has extended cancer research far
      beyond protein coding regions that include non-coding small RNAs, such as miRNA,
      isomiR, tRNA, snoRNAs, snRNA, yRNA, 7SL, and 7SK. In this study, we performed
      small RNA profiling of 26 TNBC cell lines, and compared the abundance of non
      coding RNAs among the transcriptional subtypes of triple negative breast cancer.
      We also examined their co-expression pattern with corresponding mRNAs. This study
      provides a detailed description of small RNA expression in triple-negative breast
      cancer cell lines that can aid in the development of future biomarker and novel
      targeted therapies.

PMID- 29320461
TI  - Factors Associated with Binge Eating Behavior among Malaysian Adolescents.
AB  - Although there are numerous studies on binge eating behavior in the Western
      countries, studies on this behavior in Malaysia are still limited. Therefore,
      this cross-sectional study aimed to determine the risk factors associated with
      binge eating behavior among adolescents in Malaysia. The study included 356
      adolescents (42.7% males and 57.3% females), aged 13 to 16 years. They completed
      a self-administered questionnaire on demographic and socioeconomic backgrounds,
      frequency of family meals, family meal environments, family cohesion, perception
      of body size, self-esteem, depressive symptoms, perfectionistic self
      presentation, and binge eating behavior. Furthermore, their weight, height, and
      waist circumference were measured. It was found that 14.0% of the participants
      engaged in binge eating behavior (15.2% in females and 12.5% in males).
      Additionally, it was identified that high levels of depressive symptoms, high
      levels of body dissatisfaction, poor family cohesion, and low self-esteem were
      significantly contributed to binge eating behavior after controlling for sex
      (adjusted R2 = 0.165, F = 15.056, p < 0.001). The findings may suggest that
      improving the relationships between family members, along with eliminating
      adolescents' negative emotions could help in the prevention of binge eating
      behavior among adolescents. The identified modifiable risk factors should be
      incorporated into binge eating preventive programs to increase the effectiveness
      of the programs.

PMID- 29320463
TI  - A Continuous Identity Authentication Scheme Based on Physiological and Behavioral
      Characteristics.
AB  - Wearable devices have flourished over the past ten years providing great
      advantages to people and, recently, they have also been used for identity
      authentication. Most of the authentication methods adopt a one-time
      authentication manner which cannot provide continuous certification. To address
      this issue, we present a two-step authentication method based on an own-built
      fingertip sensor device which can capture motion data (e.g., acceleration and
      angular velocity) and physiological data (e.g., a photoplethysmography (PPG)
      signal) simultaneously. When the device is worn on the user's fingertip, it will
      automatically recognize whether the wearer is a legitimate user or not. More
      specifically, multisensor data is collected and analyzed to extract
      representative and intensive features. Then, human activity recognition is
      applied as the first step to enhance the practicability of the authentication
      system. After correctly discriminating the motion state, a one-class machine
      learning algorithm is applied for identity authentication as the second step.
      When a user wears the device, the authentication process is carried on
      automatically at set intervals. Analyses were conducted using data from 40
      individuals across various operational scenarios. Extensive experiments were
      executed to examine the effectiveness of the proposed approach, which achieved an
      average accuracy rate of 98.5% and an F1-score of 86.67%. Our results suggest
      that the proposed scheme provides a feasible and practical solution for
      authentication.

PMID- 29320462
TI  - Unsaturated Fatty Acids Affect Quorum Sensing Communication System and Inhibit
      Motility and Biofilm Formation of Acinetobacter baumannii.
AB  - The increasing threat of Acinetobacter baumannii as a nosocomial pathogen is
      mainly due to the occurrence of multidrug-resistant strains that are associated
      with the real problem of its eradication from hospital wards. The particular
      ability of this pathogen to form biofilms contributes to its persistence,
      increases antibiotic resistance, and promotes persistent/device-related
      infections. We previously demonstrated that virstatin, which is a small organic
      compound known to decrease virulence of Vibrio cholera via an inhibition of T4
      pili expression, displayed very promising activity to prevent A. baumannii
      biofilm development. Here, we examined the antibiofilm activity of mono
      unsaturated chain fatty acids, palmitoleic (PoA), and myristoleic (MoA) acids,
      presenting similar action on V. cholerae virulence. We demonstrated that PoA and
      MoA (at 0.02 mg/mL) were able to decrease A. baumannii ATCC 17978 biofilm
      formation up to 38% and 24%, respectively, presented a biofilm dispersing effect
      and drastically reduced motility. We highlighted that these fatty acids decreased
      the expression of the regulator abaR from the LuxIR-type quorum sensing (QS)
      communication system AbaIR and consequently reduced the N-acyl-homoserine lactone
      production (AHL). This effect can be countered by addition of exogenous AHLs.
      Besides, fatty acids may have additional non-targeted effects, independent from
      QS. Atomic force microscopy experiments probed indeed that PoA and MoA could also
      act on the initial adhesion process in modifying the material interface
      properties. Evaluation of fatty acids effect on 22 clinical isolates showed a
      strain-dependent antibiofilm activity, which was not correlated to hydrophobicity
      or pellicle formation ability of the tested strains, and suggested a real
      diversity in cell-to-cell communication systems involved in A. baumannii biofilm
      formation.

PMID- 29320464
TI  - STI Knowledge in Berlin Adolescents.
AB  - Sexually transmitted infections (STIs) pose a significant threat to individual
      and public health. They disproportionately affect adolescents and young adults.
      In a cross-sectional study, we assessed self-rated and factual STI knowledge in a
      sample of 9th graders in 13 secondary schools in Berlin, Germany. Differences by
      age, gender, migrant background, and school type were quantified using bivariate
      and multivariable analyses. A total of 1177 students in 61 classes participated.
      The mean age was 14.6 (SD = 0.7), 47.5% were female, and 52.9% had at least one
      immigrant parent. Knowledge of human immunodeficiency virus (HIV) was widespread,
      but other STIs were less known. For example, 46.2% had never heard of chlamydia,
      10.8% knew of the HPV vaccination, and only 2.2% were aware that no cure exists
      for HPV infection. While boys were more likely to describe their knowledge as
      good, there was no general gender superiority in factual knowledge. Children of
      immigrants and students in the least academic schools had lower knowledge
      overall. Our results show that despite their particular risk to contract an STI,
      adolescents suffer from suboptimal levels of knowledge on STIs beyond HIV. Urgent
      efforts needed to improve adolescent STI knowledge in order to improve the uptake
      of primary and secondary prevention.

PMID- 29320466
TI  - An Efficient Wireless Sensor Network for Industrial Monitoring and Control.
AB  - This paper presents the design of a wireless sensor network particularly designed
      for remote monitoring and control of industrial parameters. The article describes
      the network components, protocol and sensor deployment, aimed to accomplish
      industrial constraint and to assure reliability and low power consumption. A
      particular case of study is presented. The system consists of a base station, gas
      sensing nodes, a tree-based routing scheme for the wireless sensor nodes and a
      real-time monitoring application that operates from a remote computer and a
      mobile phone. The system assures that the industrial safety quality and the
      measurement and monitoring system achieves an efficient industrial monitoring
      operations. The robustness of the developed system and the security in the
      communications have been guaranteed both in hardware and software level. The
      system is flexible and can be adapted to different environments. The testing of
      the system confirms the feasibility of the proposed implementation and validates
      the functional requirements of the developed devices, the networking solution and
      the power consumption management.

PMID- 29320467
TI  - Accurate Natural Trail Detection Using a Combination of a Deep Neural Network and
      Dynamic Programming.
AB  - This paper presents a vision sensor-based solution to the challenging problem of
      detecting and following trails in highly unstructured natural environments like
      forests, rural areas and mountains, using a combination of a deep neural network
      and dynamic programming. The deep neural network (DNN) concept has recently
      emerged as a very effective tool for processing vision sensor signals. A patch
      based DNN is trained with supervised data to classify fixed-size image patches
      into "trail" and "non-trail" categories, and reshaped to a fully convolutional
      architecture to produce trail segmentation map for arbitrary-sized input images.
      As trail and non-trail patches do not exhibit clearly defined shapes or forms,
      the patch-based classifier is prone to misclassification, and produces sub
      optimal trail segmentation maps. Dynamic programming is introduced to find an
      optimal trail on the sub-optimal DNN output map. Experimental results showing
      accurate trail detection for real-world trail datasets captured with a head
      mounted vision system are presented.

PMID- 29320465
TI  - CRP Genotypes Predict Increased Risk to Co-Present with Low Vitamin D and
      Elevated CRP in a Group of Healthy Black South African Women.
AB  - Low 25-hydroxyvitamin D (25(OH)D) and elevated C-reactive protein (CRP)
      concentrations are independently associated with adverse health outcomes,
      including cardiovascular disease (CVD). Although an inverse association between
      these factors has been described, the underlying mechanisms remain unknown. We
      postulate that environment-gene interactions, through which 25(OH)D interacts
      with single nucleotide polymorphisms (SNPs) within the CRP gene, modulate CRP;
      that certain CRP genotypes predispose individuals to a co-phenotype of low
      25(OH)D and elevated CRP concentrations; and that this co-phenotype is associated
      with higher CVD risk. Twelve CRP SNPs were genotyped, and both 25(OH)D and CRP
      were quantified, in 505 black South African women. Alarmingly, 66% and 60% of the
      women presented with deficient/insufficient 25(OH)D and elevated CRP
      concentrations, respectively. CRP concentrations were higher in individuals with
      lower 25(OH)D concentrations. However, no 25(OH)D-CRP genotype interactions were
      evident. Several genotypes were associated with an altered risk of presenting
      with the co-phenotype, indicating a genetic predisposition. Women presenting with
      this co-phenotype had higher blood pressure and increased anthropometric
      measures, which may predispose them to develop CVD. We recommend increasing
      vitamin D fortification and supplementation efforts to reduce inflammation among
      black women with vitamin D deficiency, thereby possibly curbing diseases
      contingent on the co-phenotype described here.

PMID- 29320468
TI  - Clinical Remission of Cutaneous Squamous Cell Carcinoma of the Auricle with
      Cetuximab and Nivolumab.
AB  - Cutaneous squamous cell carcinomas (SCC) affecting the regions of the head and
      neck can be challenging to resect surgically and refractory to chemotherapy or
      radiation therapy. Consequently; the treatment of squamous cell carcinomas of the
      skin is a focus of current research. One such advancement is immunotherapy.
      Herein we describe clinical remission of invasive, poorly differentiated squamous
      cell carcinoma of the pre-auricular region with external auditory canal
      involvement using cetuximab, an epidermal growth factor receptor (EGFR) antibody;
      and nivolumab, a programmed death receptor-1 (PD-1) antibody. Such durable and
      comprehensive disease resolution demonstrates the therapeutic potential of
      cetuximab and nivolumab in surgically challenging, treatment-resistant cutaneous
      squamous cell carcinoma.

PMID- 29320469
TI  - Evaluation of the Simultaneous Production of Xylitol and Ethanol from Sisal
      Fiber.
AB  - Recent years have seen an increase in the use of lignocellulosic materials in the
      development of bioproducts. Because sisal fiber is a low cost raw material and is
      readily available, this work aimed to evaluate its hemicellulose fraction for the
      simultaneous production of xylitol and ethanol. The sisal fiber presented a
      higher hemicellulose content than other frequently-employed biomasses, such as
      sugarcane bagasse. A pretreatment with dilute acid and low temperatures was
      conducted in order to obtain the hemicellulose fraction. The highest xylose
      contents (0.132 g.g-1 of sisal fiber) were obtained at 120  degrees C with 2.5%
      (v/v) of sulfuric acid. The yeast Candida tropicalis CCT 1516 was used in the
      fermentation. In the sisal fiber hemicellulose hydrolysate, the maximum
      production of xylitol (0.32 g.g-1) and of ethanol (0.27 g.g-1) was achieved in 60
      h. Thus, sisal fiber presents as a potential biomass for the production of
      ethanol and xylitol, creating value with the use of hemicellulosic liquor without
      detoxification and without the additional steps of alkaline pretreatment.

PMID- 29320470
TI  - Unexpected Ground-State Structure and Mechanical Properties of Ir2Zr
      Intermetallic Compound.
AB  - Using an unbiased structure searching method, a new orthorhombic Cmmm structure
      consisting of ZrIr12 polyhedron building blocks is predicted to be the
      thermodynamic ground-state of stoichiometric intermetallic Ir2Zr in Ir-Zr
      systems. The formation enthalpy of the Cmmm structure is considerably lower than
      that of the previously synthesized Cu2Mg-type phase, by ~107 meV/atom, as
      demonstrated by the calculation of formation enthalpy. Meanwhile, the phonon
      dispersion calculations further confirmed the dynamical stability of Cmmm phase
      under ambient conditions. The mechanical properties, including elastic stability,
      rigidity, and incompressibility, as well as the elastic anisotropy of Cmmm-Ir2Zr
      intermetallic, have thus been fully determined. It is found that the predicted
      Cmmm phase exhibits nearly elastic isotropic and great resistance to shear
      deformations within the (100) crystal plane. Evidence of atomic bonding related
      to the structural stability for Ir2Zr were manifested by calculations of the
      electronic structures.

PMID- 29320471
TI  - Achieving High Strength and Good Ductility in As-Extruded Mg-Gd-Y-Zn Alloys by Ce
      Micro-Alloying.
AB  - In this study, the effect of Ce additions on microstructure evolution of Mg-7Gd
      3.5Y-0.3Zn (wt %) alloys during the casting, homogenization, aging and extrusion
      processing are investigated, and novel mechanical properties are also obtained.
      The results show that Ce addition promotes the formation of long period stacking
      ordered (LPSO) phases in the as-cast Mg-Gd-Y-Zn-Ce alloys. A high content of Ce
      addition would reduce the maximum solubility of Gd and Y in the Mg matrix, which
      leads to the higher density of Mg12Ce phases in the as-homogenized alloys. The
      major second phases observed in the as-extruded alloys are micron-sized bulk LPSO
      phases, nano-sized stripe LPSO phases, and broken Mg12Ce and Mg5RE phases.
      Recrystallized grain size of the as-extruded 0.2Ce, 0.5Ce and 1.0Ce alloys can be
      refined to ~4.3 MUm, ~1.0 MUm and ~8.4 MUm, respectively, which is caused by the
      synthesized effect of both micron phases and nano phases. The strength and
      ductility of as-extruded samples firstly increase and then decrease with
      increasing Ce content. As-extruded 0.5Ce alloy exhibits optimal mechanical
      properties, with ultimate strength of 365 MPa and ductility of ~15%
      simultaneously.

PMID- 29320472
TI  - Subjective Complaints of Ocular Dryness and Xerostomia Among the Non-Sjogren
      Adult Population of Lublin Region, Poland.
AB  - BACKGROUND Eye and mouth dryness are the most common symptoms reported during
      ophthalmological and dental examinations, and their frequency increases with age.
      In connection with population aging and the huge variety of factors and
      conditions that can induce this condition, it is becoming a serious and growing
      problem. The purpose of the present study was to determine whether ocular dryness
      and concomitant xerostomia is associated with particular systemic diseases.
      MATERIAL AND METHODS We enrolled 642 non-Sjogren patients referred for
      examination to the ophthalmology or dental clinic of Lublin region, Poland. The
      research was conducted using a standardized interview: The Interview and
      Examination Questionnaire. All patients responded to the survey questions, which
      concerned systemic diseases, lifestyle, with special emphasis on computer work,
      spending time in polluted and air-conditioned rooms, and subsequent questions
      about the subjective symptoms of ocular and mouth dryness. RESULTS There were 424
      patients who presented signs and symptoms of both ocular and mouth dryness. Our
      study showed a statistically significant association between this condition and
      the age and sex of the patients and systemic diseases such as hypertension
      (p=0.0000), cardiovascular disease (p=0.057), and stress (p=0.036), and time
      spent at the computer (p=0.00015). CONCLUSIONS Ocular dryness and concomitant
      xerostomia may occur in apparently healthy individuals, but is more frequent in
      patients with systemic disorders. The lack of dry eye and dry mouth symptoms does
      not exclude insufficient tearing and salivation; thus, the disorders are usually
      underestimated. Our study indicates that ocular and mouth dryness are the most
      common conditions seen in out-patients, due to increased use of medications,
      computers, and air conditioning.

PMID- 29320473
TI  - Systems of mechanized and reactive droplets powered by multi-responsive
      surfactants.
AB  - Although 'active' surfactants, which are responsive to individual external
      stimuli such as temperature, electric or magnetic fields, light, redox processes
      or chemical agents, are well known, it would be interesting to combine several of
      these properties within one surfactant species. Such multi-responsive surfactants
      could provide ways of manipulating individual droplets and possibly assembling
      them into larger systems of dynamic reactors. Here we describe surfactants based
      on functionalized nanoparticle dimers that combine all of these and several other
      characteristics. These surfactants and therefore the droplets that they cover are
      simultaneously addressable by magnetic, optical and electric fields. As a result,
      the surfactant-covered droplets can be assembled into various hierarchical
      structures, including dynamic ones, in which light powers the rapid rotation of
      the droplets. Such rotating droplets can transfer mechanical torques to their non
      nearest neighbours, thus acting like systems of mechanical gears. Furthermore,
      droplets of different types can be merged by applying electric fields and, owing
      to interfacial jamming, can form complex, non-spherical, 'patchy' structures with
      different surface regions covered with different surfactants. In systems of
      droplets that carry different chemicals, combinations of multiple stimuli can be
      used to control the orientations of the droplets, inter-droplet transport, mixing
      of contents and, ultimately, sequences of chemical reactions. Overall, the multi
      responsive active surfactants that we describe provide an unprecedented level of
      flexibility with which liquid droplets can be manipulated, assembled and reacted.

PMID- 29320475
TI  - Warfare and wildlife declines in Africa's protected areas.
AB  - Large-mammal populations are ecological linchpins, and their worldwide decline
      and extinction disrupts many ecosystem functions and services. Reversal of this
      trend will require an understanding of the determinants of population decline, to
      enable more accurate predictions of when and where collapses will occur and to
      guide the development of effective conservation and restoration policies. Many
      correlates of large-mammal declines are known, including low reproductive rates,
      overhunting, and habitat destruction. However, persistent uncertainty about the
      effects of one widespread factor-armed conflict-complicates conservation-planning
      and priority-setting efforts. Case studies have revealed that conflict can have
      either positive or negative local impacts on wildlife, but the direction and
      magnitude of its net effect over large spatiotemporal scales have not previously
      been quantified. Here we show that conflict frequency predicts the occurrence and
      severity of population declines among wild large herbivores in African protected
      areas from 1946 to 2010. Conflict was extensive during this period, occurring in
      71% of protected areas, and conflict frequency was the single most important
      predictor of wildlife population trends among the variables that we analysed.
      Population trajectories were stable in peacetime, fell significantly below
      replacement with only slight increases in conflict frequency (one conflict-year
      per two-to-five decades), and were almost invariably negative in high-conflict
      sites, both in the full 65-year dataset and in an analysis restricted to recent
      decades (1989-2010). Yet total population collapse was infrequent, indicating
      that war-torn faunas can often recover. Human population density was also
      correlated (positively) with wildlife population trajectories in recent years;
      however, we found no significant effect, in either timespan, of species body
      mass, protected-area size, conflict intensity (human fatalities), drought
      frequency, presence of extractable mineral resources, or various metrics of
      development and governance. Our results suggest that sustained conservation
      activity in conflict zones-and rapid interventions following ceasefires-may help
      to save many at-risk populations and species.

PMID- 29320474
TI  - High response rate to PD-1 blockade in desmoplastic melanomas.
AB  - Desmoplastic melanoma is a rare subtype of melanoma characterized by dense
      fibrous stroma, resistance to chemotherapy and a lack of actionable driver
      mutations, and is highly associated with ultraviolet light-induced DNA damage. We
      analysed sixty patients with advanced desmoplastic melanoma who had been treated
      with antibodies to block programmed cell death 1 (PD-1) or PD-1 ligand (PD-L1).
      Objective tumour responses were observed in forty-two of the sixty patients (70%;
      95% confidence interval 57-81%), including nineteen patients (32%) with a
      complete response. Whole-exome sequencing revealed a high mutational load and
      frequent NF1 mutations (fourteen out of seventeen cases) in these tumours.
      Immunohistochemistry analysis from nineteen desmoplastic melanomas and thirteen
      non-desmoplastic melanomas revealed a higher percentage of PD-L1-positive cells
      in the tumour parenchyma in desmoplastic melanomas (P = 0.04); these cells were
      highly associated with increased CD8 density and PD-L1 expression in the tumour
      invasive margin. Therefore, patients with advanced desmoplastic melanoma derive
      substantial clinical benefit from PD-1 or PD-L1 immune checkpoint blockade
      therapy, even though desmoplastic melanoma is defined by its dense desmoplastic
      fibrous stroma. The benefit is likely to result from the high mutational burden
      and a frequent pre-existing adaptive immune response limited by PD-L1 expression.

PMID- 29320476
TI  - Erratum: Runx3 programs CD8+ T cell residency in non-lymphoid tissues and
      tumours.
AB  - This corrects the article DOI: 10.1038/nature24993.

PMID- 29320477
TI  - A global map of travel time to cities to assess inequalities in accessibility in
      2015.
AB  - The economic and man-made resources that sustain human wellbeing are not
      distributed evenly across the world, but are instead heavily concentrated in
      cities. Poor access to opportunities and services offered by urban centres (a
      function of distance, transport infrastructure, and the spatial distribution of
      cities) is a major barrier to improved livelihoods and overall development.
      Advancing accessibility worldwide underpins the equity agenda of 'leaving no one
      behind' established by the Sustainable Development Goals of the United Nations.
      This has renewed international efforts to accurately measure accessibility and
      generate a metric that can inform the design and implementation of development
      policies. The only previous attempt to reliably map accessibility worldwide,
      which was published nearly a decade ago, predated the baseline for the
      Sustainable Development Goals and excluded the recent expansion in infrastructure
      networks, particularly in lower-resource settings. In parallel, new data sources
      provided by Open Street Map and Google now capture transportation networks with
      unprecedented detail and precision. Here we develop and validate a map that
      quantifies travel time to cities for 2015 at a spatial resolution of
      approximately one by one kilometre by integrating ten global-scale surfaces that
      characterize factors affecting human movement rates and 13,840 high-density urban
      centres within an established geospatial-modelling framework. Our results
      highlight disparities in accessibility relative to wealth as 50.9% of individuals
      living in low-income settings (concentrated in sub-Saharan Africa) reside within
      an hour of a city compared to 90.7% of individuals in high-income settings. By
      further triangulating this map against socioeconomic datasets, we demonstrate how
      access to urban centres stratifies the economic, educational, and health status
      of humanity.

PMID- 29320478
TI  - An extracellular network of Arabidopsis leucine-rich repeat receptor kinases.
AB  - The cells of multicellular organisms receive extracellular signals using surface
      receptors. The extracellular domains (ECDs) of cell surface receptors function as
      interaction platforms, and as regulatory modules of receptor activation.
      Understanding how interactions between ECDs produce signal-competent receptor
      complexes is challenging because of their low biochemical tractability. In
      plants, the discovery of ECD interactions is complicated by the massive expansion
      of receptor families, which creates tremendous potential for changeover in
      receptor interactions. The largest of these families in Arabidopsis thaliana
      consists of 225 evolutionarily related leucine-rich repeat receptor kinases (LRR
      RKs), which function in the sensing of microorganisms, cell expansion, stomata
      development and stem-cell maintenance. Although the principles that govern LRR-RK
      signalling activation are emerging, the systems-level organization of this family
      of proteins is unknown. Here, to address this, we investigated 40,000 potential
      ECD interactions using a sensitized high-throughput interaction assay, and
      produced an LRR-based cell surface interaction network (CSILRR) that consists of
      567 interactions. To demonstrate the power of CSILRR for detecting biologically
      relevant interactions, we predicted and validated the functions of
      uncharacterized LRR-RKs in plant growth and immunity. In addition, we show that
      CSILRR operates as a unified regulatory network in which the LRR-RKs most crucial
      for its overall structure are required to prevent the aberrant signalling of
      receptors that are several network-steps away. Thus, plants have evolved LRR-RK
      networks to process extracellular signals into carefully balanced responses.

PMID- 29320479
TI  - Paternal chromosome loss and metabolic crisis contribute to hybrid inviability in
      Xenopus.
AB  - Hybridization of eggs and sperm from closely related species can give rise to
      genetic diversity, or can lead to embryo inviability owing to incompatibility.
      Although central to evolution, the cellular and molecular mechanisms underlying
      post-zygotic barriers that drive reproductive isolation and speciation remain
      largely unknown. Species of the African clawed frog Xenopus provide an ideal
      system to study hybridization and genome evolution. Xenopus laevis is an
      allotetraploid with 36 chromosomes that arose through interspecific hybridization
      of diploid progenitors, whereas Xenopus tropicalis is a diploid with 20
      chromosomes that diverged from a common ancestor approximately 48 million years
      ago. Differences in genome size between the two species are accompanied by
      organism size differences, and size scaling of the egg and subcellular structures
      such as nuclei and spindles formed in egg extracts. Nevertheless, early
      development transcriptional programs, gene expression patterns, and protein
      sequences are generally conserved. Whereas the hybrid produced when X. laevis
      eggs are fertilized by X. tropicalis sperm is viable, the reverse hybrid dies
      before gastrulation. Here we apply cell biological tools and high-throughput
      methods to study the mechanisms underlying hybrid inviability. We reveal that two
      specific X. laevis chromosomes are incompatible with the X. tropicalis cytoplasm
      and are mis-segregated during mitosis, leading to unbalanced gene expression at
      the maternal to zygotic transition, followed by cell-autonomous catastrophic
      embryo death. These results reveal a cellular mechanism underlying hybrid
      incompatibility that is driven by genome evolution and contributes to the process
      by which biological populations become distinct species.

PMID- 29320480
TI  - Pharmacological activation of REV-ERBs is lethal in cancer and oncogene-induced
      senescence.
AB  - The circadian clock imposes daily rhythms in cell proliferation, metabolism,
      inflammation and DNA damage response. Perturbations of these processes are
      hallmarks of cancer and chronic circadian rhythm disruption predisposes
      individuals to tumour development. This raises the hypothesis that
      pharmacological modulation of the circadian machinery may be an effective
      therapeutic strategy for combating cancer. REV-ERBs, the nuclear hormone
      receptors REV-ERBalpha (also known as NR1D1) and REV-ERBbeta (also known as
      NR1D2), are essential components of the circadian clock. Here we show that two
      agonists of REV-ERBs-SR9009 and SR9011-are specifically lethal to cancer cells
      and oncogene-induced senescent cells, including melanocytic naevi, and have no
      effect on the viability of normal cells or tissues. The anticancer activity of
      SR9009 and SR9011 affects a number of oncogenic drivers (such as HRAS, BRAF,
      PIK3CA and others) and persists in the absence of p53 and under hypoxic
      conditions. The regulation of autophagy and de novo lipogenesis by SR9009 and
      SR9011 has a critical role in evoking an apoptotic response in malignant cells.
      Notably, the selective anticancer properties of these REV-ERB agonists impair
      glioblastoma growth in vivo and improve survival without causing overt toxicity
      in mice. These results indicate that pharmacological modulation of circadian
      regulators is an effective antitumour strategy, identifying a class of anticancer
      agents with a wide therapeutic window. We propose that REV-ERB agonists are
      inhibitors of autophagy and de novo lipogenesis, with selective activity towards
      malignant and benign neoplasms.

PMID- 29320481
TI  - Architecture of a channel-forming O-antigen polysaccharide ABC transporter.
AB  - O-antigens are cell surface polysaccharides of many Gram-negative pathogens that
      aid in escaping innate immune responses. A widespread O-antigen biosynthesis
      mechanism involves the synthesis of the lipid-anchored polymer on the cytosolic
      face of the inner membrane, followed by transport to the periplasmic side where
      it is ligated to the lipid A core to complete a lipopolysaccharide molecule. In
      this pathway, transport to the periplasm is mediated by an ATP-binding cassette
      (ABC) transporter, called Wzm-Wzt. Here we present the crystal structure of the
      Wzm-Wzt homologue from Aquifex aeolicus in an open conformation. The transporter
      forms a transmembrane channel that is sufficiently wide to accommodate a linear
      polysaccharide. Its nucleotide-binding domain and a periplasmic extension form
      'gate helices' at the cytosolic and periplasmic membrane interfaces that probably
      serve as substrate entry and exit points. Site-directed mutagenesis of the gates
      impairs in vivo O-antigen secretion in the Escherichia coli prototype. Combined
      with a closed structure of the isolated nucleotide-binding domains, our
      structural and functional analyses suggest a processive O-antigen translocation
      mechanism, which stands in contrast to the classical alternating access mechanism
      of ABC transporters.

PMID- 29320482
TI  - Severe retinopathy of prematurity is associated with reduced cerebellar and
      brainstem volumes at term and neurodevelopmental deficits at 2 years.
AB  - BackgroundTo evaluate the association between severe retinopathy of prematurity
      (ROP), measures of brain morphology at term-equivalent age (TEA), and
      neurodevelopmental outcome.MethodsEighteen infants with severe ROP (median
      gestational age (GA) 25.3 (range 24.6-25.9 weeks) were included in this
      retrospective case-control study. Each infant was matched to two extremely
      preterm control infants (n=36) by GA, birth weight, sex, and brain injury. T2
      weighted images were obtained on a 3 T magnetic resonance imaging (MRI) at TEA.
      Brain volumes were computed using an automatic segmentation method. In addition,
      cortical folding metrics were extracted. Neurodevelopment was formally assessed
      at the ages of 15 and 24 months.ResultsInfants with severe ROP had smaller
      cerebellar volumes (21.4+/-3.2 vs. 23.1+/-2.6 ml; P=0.04) and brainstem volumes
      (5.4+/-0.5 ml vs. 5.8+/-0.5 ml; P=0.01) compared with matched control infants.
      Furthermore, ROP patients showed a significantly lower development quotient
      (Griffiths Mental Development Scales) at the age of 15 months (93+/-15 vs. 102+/
      10; P=0.01) and lower fine motor scores (10+/-3 vs. 12+/-2; P=0.02) on Bayley
      Scales (Third Edition) at the age of 24 months.ConclusionSevere ROP was
      associated with smaller volumes of the cerebellum and brainstem and with poorer
      early neurodevelopmental outcome. Follow-up through childhood is needed to
      evaluate the long-term consequences of our findings.

PMID- 29320483
TI  - Microarray analysis in pregnancies with isolated unilateral kidney agenesis.
AB  - BackgroundThe objective of our study was to examine the risk for submicroscopic
      chromosomal aberrations among fetuses with apparently isolated solitary
      kidney.MethodsData acquisition was performed retrospectively by searching Israeli
      Ministry of Health-computerized database. All cases having chromosomal microarray
      analysis (CMA), referred because of an indication of isolated unilateral kidney
      agenesis between January 2013 and September 2016, were included. Rate of
      clinically significant CMA findings in these pregnancies was compared to
      pregnancies with normal ultrasound, based on a systematic review encompassing
      9,792 cases and local data of 5,541 pregnancies undergoing CMA because of
      maternal request.ResultsOf the 81 pregnancies with isolated solitary kidney, 2
      (2.47%) loss-of-copy number variants compatible with well-described deletion
      syndromes were reported (16p11.2-16p12.2 and 22q11.21 microdeletion syndromes).
      In addition, one variant of unknown significance was demonstrated. The relative
      risk for pathogenic CMA findings among pregnancies with isolated unilateral renal
      agenesis was not significantly different compared with the control
      population.ConclusionCMA analysis in pregnancies with unilateral renal agenesis
      might still be useful, to the same degree as it can be in the general population.

PMID- 29320484
TI  - Brain growth in the NICU: critical periods of tissue-specific expansion.
AB  - ObjectiveTo examine, using serial magnetic resonance imaging (MRI), total and
      tissue-specific brain growth in very-preterm (VPT) infants during the period that
      coincides with the early and late stages of the third trimester.MethodsStructural
      MRI scans were collected from two prospective cohorts of VPT infants (<=30 weeks
      of gestation). A total of 51 MRI scans from 18 VPT subjects were available for
      volumetric analysis. Brain tissue was classified into cerebrospinal fluid,
      cortical gray matter, myelinated and unmyelinated white matter, deep nuclear gray
      matter, and cerebellum. Nine infants had sufficient serial scans to allow
      comparison of tissue growth during the periods corresponding to the early and
      late stages of the third trimester.ResultsTissue-specific differences in ex utero
      brain growth trajectories were observed in the period corresponding to the third
      trimester. Most notably, there was a marked increase in cortical gray matter
      expansion from 34 to 40 weeks of postmenstrual age, emphasizing this critical
      period of brain development.ConclusionUtilizing serial MRI to document early
      brain development in VPT infants, this study documents regional differences in
      brain growth trajectories ex utero during the period corresponding to the first
      and second half of the third trimester, providing novel insight into the
      maturational vulnerability of the rapidly expanding cortical gray matter in the
      NICU.

PMID- 29320485
TI  - Non-invasive ventilation and surfactant treatment as the primary mode of
      respiratory support in surfactant-deficient newborn piglets.
AB  - BackgroundNasal continuous positive airway pressure (NCPAP) and nasal
      intermittent positive pressure ventilation (NIPPV), forms of non-invasive
      ventilation (NIV) for respiratory support, are increasingly being chosen as the
      initial treatment for neonates with surfactant (SF) deficiency. Our objective was
      to compare NCPAP with NIPPV with or without SF administration as a primary mode
      of ventilation.MethodsTwenty-four newborn piglets with SF-deficient lung injury
      produced by repetitive bronchoalveolar lavages were randomly assigned to NCPAP or
      NIPPV, with or without SF administration (InSurE method). We evaluated pulmonary,
      systemic (hemodynamic and oxygen metabolism), and cerebral effects.ResultsSF
      deficient piglets developed respiratory distress (FiO2:1, pH<7.2, PaCO2>70 mm Hg,
      PaO2<70 mm Hg, and Cdyn<0.5 ml/cmH2O/kg). Gradual improvements in pulmonary
      status were observed in both NIV groups, with NIPPV achieving lower lung
      inflammation markers and injury scores. Both SF-treated groups obtained
      significantly better respiratory outcomes than groups not treated with SF before
      NIV. All NIV-treated groups showed low brain injury scores.ConclusionIn
      spontaneously breathing SF-deficient newborn piglets, NIPPV is a suitable NIV
      strategy. SF administration in combination with NCPAP or NIPPV improves pulmonary
      status providing extra protection against pulmonary injury. No injury to the
      developing brain was observed to be associated with these NIV strategies, with or
      without SF therapy.

PMID- 29320486
TI  - Systematic characterization of maturation time of fluorescent proteins in living
      cells.
AB  - The slow maturation time of fluorescent proteins (FPs) limits the temporal
      accuracy of measurements of rapid processes such as gene expression dynamics and
      effectively reduces fluorescence signal in growing cells. We used high-precision
      time-lapse microscopy to characterize the maturation kinetics of 50 FPs that span
      the visible spectrum at two different temperatures in Escherichia coli cells. We
      identified fast-maturing FPs from this set that yielded the highest signal-to
      noise ratio and temporal resolution in individual growing cells.

PMID- 29320487
TI  - Multicolor quantitative confocal imaging cytometry.
AB  - Multicolor 3D quantitative imaging of large tissue volumes is necessary to
      understand tissue development and organization as well as interactions between
      distinct cell types in situ. However, tissue imaging remains technically
      challenging, particularly imaging of bone and marrow. Here, we describe a
      pipeline to reproducibly generate high-dimensional quantitative data from bone
      and bone marrow that may be extended to any tissue. We generate thick bone
      sections from adult mouse femurs with preserved tissue microarchitecture and
      demonstrate eight-color imaging using confocal microscopy without linear
      unmixing. We introduce XiT, an open-access software for fast and easy data
      curation, exploration and quantification of large imaging data sets with single
      cell resolution. We describe how XiT can be used to correct for potential
      artifacts in quantitative 3D imaging, and we use the pipeline to measure the
      spatial relationship between hematopoietic cells, bone matrix and marrow Schwann
      cells.

PMID- 29320488
TI  - Analysis of ferrite nanoparticles in the flow of ferromagnetic nanofluid.
AB  - Theoretical analysis has been carried out to establish the heat transport
      phenomenon of six different ferromagnetic MnZnFe2O4-C2H6O2 (manganese zinc
      ferrite-ethylene glycol), NiZnFe2O4-C2H6O2 (Nickel zinc ferrite-ethylene glycol),
      Fe2O4-C2H6O2 (magnetite ferrite-ethylene glycol), NiZnFe2O4-H2O (Nickel zinc
      ferrite-water), MnZnFe2O4-H2O (manganese zinc ferrite-water), and Fe2O4-H2O
      (magnetite ferrite-water) nanofluids containing manganese zinc ferrite, Nickel
      zinc ferrite, and magnetite ferrite nanoparticles dispersed in a base fluid of
      ethylene glycol and water mixture. The performance of convective heat transfer is
      elevated in boundary layer flow region via nanoparticles. Magnetic dipole in
      presence of ferrites nanoparticles plays a vital role in controlling the thermal
      and momentum boundary layers. In perspective of this, the impacts of magnetic
      dipole on the nano boundary layer, steady, and laminar flow of incompressible
      ferromagnetic nanofluids are analyzed in the present study. Flow is caused by
      linear stretching of the surface. Fourier's law of heat conduction is used in the
      evaluation of heat flux. Impacts of emerging parameters on the magneto
      thermomechanical coupling are analyzed numerically. Further, it is evident that
      Newtonian heating has increasing behavior on the rate of heat transfer in the
      boundary layer. Comparison with available results for specific cases show an
      excellent agreement.

PMID- 29320489
TI  - Study of gas production from shale reservoirs with multi-stage hydraulic
      fracturing horizontal well considering multiple transport mechanisms.
AB  - Development of unconventional shale gas reservoirs (SGRs) has been boosted by the
      advancements in two key technologies: horizontal drilling and multi-stage
      hydraulic fracturing. A large number of multi-stage fractured horizontal wells
      (MsFHW) have been drilled to enhance reservoir production performance. Gas flow
      in SGRs is a multi-mechanism process, including: desorption, diffusion, and non
      Darcy flow. The productivity of the SGRs with MsFHW is influenced by both
      reservoir conditions and hydraulic fracture properties. However, rare simulation
      work has been conducted for multi-stage hydraulic fractured SGRs. Most of them
      use well testing methods, which have too many unrealistic simplifications and
      assumptions. Also, no systematical work has been conducted considering all
      reasonable transport mechanisms. And there are very few works on sensitivity
      studies of uncertain parameters using real parameter ranges. Hence, a detailed
      and systematic study of reservoir simulation with MsFHW is still necessary. In
      this paper, a dual porosity model was constructed to estimate the effect of
      parameters on shale gas production with MsFHW. The simulation model was verified
      with the available field data from the Barnett Shale. The following mechanisms
      have been considered in this model: viscous flow, slip flow, Knudsen diffusion,
      and gas desorption. Langmuir isotherm was used to simulate the gas desorption
      process. Sensitivity analysis on SGRs' production performance with MsFHW has been
      conducted. Parameters influencing shale gas production were classified into two
      categories: reservoir parameters including matrix permeability, matrix porosity;
      and hydraulic fracture parameters including hydraulic fracture spacing, and
      fracture half-length. Typical ranges of matrix parameters have been reviewed.
      Sensitivity analysis have been conducted to analyze the effect of the above
      factors on the production performance of SGRs. Through comparison, it can be
      found that hydraulic fracture parameters are more sensitive compared with
      reservoir parameters. And reservoirs parameters mainly affect the later
      production period. However, the hydraulic fracture parameters have a significant
      effect on gas production from the early period. The results of this study can be
      used to improve the efficiency of history matching process. Also, it can
      contribute to the design and optimization of hydraulic fracture treatment design
      in unconventional SGRs.

PMID- 29320490
TI  - The glutamine synthetase of Trypanosoma cruzi is required for its resistance to
      ammonium accumulation and evasion of the parasitophorous vacuole during host-cell
      infection.
AB  - Trypanosoma cruzi, the etiological agent of Chagas disease, consumes glucose and
      amino acids depending on the environmental availability of each nutrient during
      its complex life cycle. For example, amino acids are the major energy and carbon
      sources in the intracellular stages of the T. cruzi parasite, but their
      consumption produces an accumulation of NH4+ in the environment, which is toxic.
      These parasites do not have a functional urea cycle to secrete excess nitrogen as
      low-toxicity waste. Glutamine synthetase (GS) plays a central role in regulating
      the carbon/nitrogen balance in the metabolism of most living organisms. We show
      here that the gene TcGS from T. cruzi encodes a functional glutamine synthetase;
      it can complement a defect in the GLN1 gene from Saccharomyces cerevisiae and
      utilizes ATP, glutamate and ammonium to yield glutamine in vitro. Overall, its
      kinetic characteristics are similar to other eukaryotic enzymes, and it is
      dependent on divalent cations. Its cytosolic/mitochondrial localization was
      confirmed by immunofluorescence. Inhibition by Methionine sulfoximine revealed
      that GS activity is indispensable under excess ammonium conditions. Coincidently,
      its expression levels are maximal in the amastigote stage of the life cycle, when
      amino acids are preferably consumed, and NH4+ production is predictable. During
      host-cell invasion, TcGS is required for the parasite to escape from the
      parasitophorous vacuole, a process sine qua non for the parasite to replicate and
      establish infection in host cells. These results are the first to establish a
      link between the activity of a metabolic enzyme and the ability of a parasite to
      reach its intracellular niche to replicate and establish host-cell infection.

PMID- 29320492
TI  - Metallochaperone UreG serves as a new target for design of urease inhibitor: A
      novel strategy for development of antimicrobials.
AB  - Urease as a potential target of antimicrobial drugs has received considerable
      attention given its versatile roles in microbial infection. Development of
      effective urease inhibitors, however, is a significant challenge due to the
      deeply buried active site and highly specific substrate of a bacterial urease.
      Conventionally, urease inhibitors are designed by either targeting the active
      site or mimicking substrate of urease, which is not efficient. Up to now, only
      one effective inhibitor-acetohydroxamic acid (AHA)-is clinically available, but
      it has adverse side effects. Herein, we demonstrate that a clinically used drug,
      colloidal bismuth subcitrate, utilizes an unusual way to inhibit urease activity,
      i.e., disruption of urease maturation process via functional perturbation of a
      metallochaperone, UreG. Similar phenomena were also observed in various
      pathogenic bacteria, suggesting that UreG may serve as a general target for
      design of new types of urease inhibitors. Using Helicobacter pylori UreG as a
      showcase, by virtual screening combined with experimental validation, we show
      that two compounds targeting UreG also efficiently inhibited urease activity with
      inhibitory concentration (IC)50 values of micromolar level, resulting in
      attenuated virulence of the pathogen. We further demonstrate the efficacy of the
      compounds in a mammalian cell infection model. This study opens up a new
      opportunity for the design of more effective urease inhibitors and clearly
      indicates that metallochaperones involved in the maturation of important
      microbial metalloenzymes serve as new targets for devising a new type of
      antimicrobial drugs.

PMID- 29320493
TI  - From macro- to microfactors in health: Social science approaches in research on
      sexually transmitted infections.
AB  - Ruth Kutalek and colleagues share their Perspective on Kipruto Chesang and
      colleagues' qualitative study of beliefs and practices among healthcare providers
      managing STIs in Kenya and discuss the value of this type of research for
      addressing biosocial challenges.

PMID- 29320494
TI  - Sexually transmitted infections in the era of antiretroviral-based HIV
      prevention: Priorities for discovery research, implementation science, and
      community involvement.
AB  - Jeanne M. Marrazzo and colleagues join PLOS Medicine's Collection on the
      prevention, diagnosis, and treatment of STIs with a Perspective on HIV research
      imperatives in our time of effective viral suppression and pre-exposure
      prophylaxis.

PMID- 29320491
TI  - Cdc73 suppresses genome instability by mediating telomere homeostasis.
AB  - Defects in the genes encoding the Paf1 complex can cause increased genome
      instability. Loss of Paf1, Cdc73, and Ctr9, but not Rtf1 or Leo1, caused
      increased accumulation of gross chromosomal rearrangements (GCRs). Combining the
      cdc73Delta mutation with individual deletions of 43 other genes, including TEL1
      and YKU80, which are involved in telomere maintenance, resulted in synergistic
      increases in GCR rates. Whole genome sequence analysis of GCRs indicated that
      there were reduced relative rates of GCRs mediated by de novo telomere additions
      and increased rates of translocations and inverted duplications in cdc73Delta
      single and double mutants. Analysis of telomere lengths and telomeric gene
      silencing in strains containing different combinations of cdc73Delta, tel1Delta
      and yku80Delta mutations suggested that combinations of these mutations caused
      increased defects in telomere maintenance. A deletion analysis of Cdc73 revealed
      that a central 105 amino acid region was necessary and sufficient for suppressing
      the defects observed in cdc73Delta strains; this region was required for the
      binding of Cdc73 to the Paf1 complex through Ctr9 and for nuclear localization of
      Cdc73. Taken together, these data suggest that the increased GCR rate of
      cdc73Delta single and double mutants is due to partial telomere dysfunction and
      that Ctr9 and Paf1 play a central role in the Paf1 complex potentially by
      scaffolding the Paf1 complex subunits or by mediating recruitment of the Paf1
      complex to the different processes it functions in.

PMID- 29320495
TI  - The WHO 2016 verbal autopsy instrument: An international standard suitable for
      automated analysis by InterVA, InSilicoVA, and Tariff 2.0.
AB  - BACKGROUND: Verbal autopsy (VA) is a practical method for determining probable
      causes of death at the population level in places where systems for medical
      certification of cause of death are weak. VA methods suitable for use in routine
      settings, such as civil registration and vital statistics (CRVS) systems, have
      developed rapidly in the last decade. These developments have been part of a
      growing global momentum to strengthen CRVS systems in low-income countries. With
      this momentum have come pressure for continued research and development of VA
      methods and the need for a single standard VA instrument on which multiple
      automated diagnostic methods can be developed. METHODS AND FINDINGS: In 2016,
      partners harmonized a WHO VA standard instrument that fully incorporates the
      indicators necessary to run currently available automated diagnostic algorithms.
      The WHO 2016 VA instrument, together with validated approaches to analyzing VA
      data, offers countries solutions to improving information about patterns of cause
      specific mortality. This VA instrument offers the opportunity to harmonize the
      automated diagnostic algorithms in the future. CONCLUSIONS: Despite all
      improvements in design and technology, VA is only recommended where medical
      certification of cause of death is not possible. The method can nevertheless
      provide sufficient information to guide public health priorities in communities
      in which physician certification of deaths is largely unavailable. The WHO 2016
      VA instrument, together with validated approaches to analyzing VA data, offers
      countries solutions to improving information about patterns of cause-specific
      mortality.

PMID- 29320496
TI  - Bayesian inference of phylogenetic networks from bi-allelic genetic markers.
AB  - Phylogenetic networks are rooted, directed, acyclic graphs that model reticulate
      evolutionary histories. Recently, statistical methods were devised for inferring
      such networks from either gene tree estimates or the sequence alignments of
      multiple unlinked loci. Bi-allelic markers, most notably single nucleotide
      polymorphisms (SNPs) and amplified fragment length polymorphisms (AFLPs), provide
      a powerful source of genome-wide data. In a recent paper, a method called SNAPP
      was introduced for statistical inference of species trees from unlinked bi
      allelic markers. The generative process assumed by the method combined both a
      model of evolution for the bi-allelic markers, as well as the multispecies
      coalescent. A novel component of the method was a polynomial-time algorithm for
      exact computation of the likelihood of a fixed species tree via integration over
      all possible gene trees for a given marker. Here we report on a method for
      Bayesian inference of phylogenetic networks from bi-allelic markers. Our method
      significantly extends the algorithm for exact computation of phylogenetic network
      likelihood via integration over all possible gene trees. Unlike the case of
      species trees, the algorithm is no longer polynomial-time on all instances of
      phylogenetic networks. Furthermore, the method utilizes a reversible-jump MCMC
      technique to sample the posterior of phylogenetic networks given bi-allelic
      marker data. Our method has a very good performance in terms of accuracy and
      robustness as we demonstrate on simulated data, as well as a data set of multiple
      New Zealand species of the plant genus Ourisia (Plantaginaceae). We implemented
      the method in the publicly available, open-source PhyloNet software package.

PMID- 29320497
TI  - Survival analysis and classification methods for forest fire size.
AB  - Factors affecting wildland-fire size distribution include weather, fuels, and
      fire suppression activities. We present a novel application of survival analysis
      to quantify the effects of these factors on a sample of sizes of lightning-caused
      fires from Alberta, Canada. Two events were observed for each fire: the size at
      initial assessment (by the first fire fighters to arrive at the scene) and the
      size at "being held" (a state when no further increase in size is expected). We
      developed a statistical classifier to try to predict cases where there will be a
      growth in fire size (i.e., the size at "being held" exceeds the size at initial
      assessment). Logistic regression was preferred over two alternative classifiers,
      with covariates consistent with similar past analyses. We conducted survival
      analysis on the group of fires exhibiting a size increase. A screening process
      selected three covariates: an index of fire weather at the day the fire started,
      the fuel type burning at initial assessment, and a factor for the type and
      capabilities of the method of initial attack. The Cox proportional hazards model
      performed better than three accelerated failure time alternatives. Both fire
      weather and fuel type were highly significant, with effects consistent with known
      fire behaviour. The effects of initial attack method were not statistically
      significant, but did suggest a reverse causality that could arise if fire
      management agencies were to dispatch resources based on a-priori assessment of
      fire growth potentials. We discuss how a more sophisticated analysis of larger
      data sets could produce unbiased estimates of fire suppression effect under such
      circumstances.

PMID- 29320498
TI  - Molecular mapping of QTL alleles of Brassica oleracea affecting days to flowering
      and photosensitivity in spring Brassica napus.
AB  - Earliness of flowering and maturity are important traits in spring Brassica napus
      canola-whether grown under long- or short-day condition. By use of a spring B.
      napus mapping population carrying the genome content of B. oleracea and testing
      this population under 10 to 18 h photoperiod and 18 to 20 0C (day) temperature
      conditions, we identified a major QTL on the chromosome C1 affecting flowering
      time without being influenced by photoperiod and temperature, and a major QTL on
      C9 affecting flowering time under a short photoperiod (10 h); in both cases, the
      QTL alleles reducing the number of days to flowering in B. napus were
      introgressed from the late flowering species B. oleracea. Additive effect of the
      C1 QTL allele at 14 to18 h photoperiod was 1.1 to 2.9 days; however, the same QTL
      allele exerted an additive effect of 6.2 days at 10 h photoperiod. Additive
      effect of the C9 QTL at 10 h photoperiod was 2.8 days. These two QTL also showed
      significant interaction in the control of flowering only under a short-day (10 h
      photoperiod) condition with an effect of 2.3 days. A few additional QTL were also
      detected on the chromosomes C2 and C8; however, none of these QTL could be
      detected under all photoperiod and temperature conditions. BLASTn search
      identified several putative flowering time genes on the chromosomes C1 and C9 and
      located the physical position of the QTL markers in the Brassica genome; however,
      only a few of these genes were found within the QTL region. Thus, the molecular
      markers and the genomic regions identified in this research could potentially be
      used in breeding for the development of early flowering photoinsensitive B. napus
      canola cultivars, as well as for identification of candidate genes involved in
      flowering time variation and photosensitivity.

PMID- 29320499
TI  - Precocious development of self-awareness in dolphins.
AB  - Mirror-self recognition (MSR) is a behavioral indicator of self-awareness in
      young children and only a few other species, including the great apes, dolphins,
      elephants and magpies. The emergence of self-awareness in children typically
      occurs during the second year and has been correlated with sensorimotor
      development and growing social and self-awareness. Comparative studies of MSR in
      chimpanzees report that the onset of this ability occurs between 2 years 4 months
      and 3 years 9 months of age. Studies of wild and captive bottlenose dolphins
      (Tursiops truncatus) have reported precocious sensorimotor and social awareness
      during the first weeks of life, but no comparative MSR research has been
      conducted with this species. We exposed two young bottlenose dolphins to an
      underwater mirror and analyzed video recordings of their behavioral responses
      over a 3-year period. Here we report that both dolphins exhibited MSR, indicated
      by self-directed behavior at the mirror, at ages earlier than generally reported
      for children and at ages much earlier than reported for chimpanzees. The early
      onset of MSR in young dolphins occurs in parallel with their advanced
      sensorimotor development, complex and reciprocal social interactions, and growing
      social awareness. Both dolphins passed subsequent mark tests at ages comparable
      with children. Thus, our findings indicate that dolphins exhibit self-awareness
      at a mirror at a younger age than previously reported for children or other
      species tested.

PMID- 29320500
TI  - Brain structural changes in cynomolgus monkeys administered with 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine: A longitudinal voxel-based morphometry and
      diffusion tensor imaging study.
AB  - In animal models of Parkinson's disease (PD), 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP) is one of the most widely used agents that damages the
      nigrostriatal dopaminergic pathway. However, brain structural changes in response
      to MPTP remain unclear. This study aimed to investigate in vivo longitudinal
      changes in gray matter (GM) volume and white matter (WM) microstructure in
      primate models administered with MPTP. In six cynomolgus monkeys, high-resolution
      magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) scans were
      acquired 7 times over 32 weeks, and assessments of motor symptoms were conducted
      over 15 months, before and after the MPTP injection. Changes in GM volume and WM
      microstructure were estimated on a voxel-by-voxel basis. Mixed-effects regression
      models were used to examine the trajectories of these structural changes. GM
      volume initially increased after the MPTP injection and gradually decreased in
      the striatum, midbrain, and other dopaminergic areas. The cerebellar volume
      temporarily decreased and returned to its baseline level. The rate of midbrain
      volume increase was positively correlated with the increase rate of motor symptom
      severity (Spearman rho = 0.93, p = 0.008). Mean, axial, and radial diffusivity in
      the striatum and frontal areas demonstrated initial increases and subsequent
      decreases. The current multi-modal imaging study of MPTP-administered monkeys
      revealed widespread and dynamic structural changes not only in the nigrostriatal
      pathway but also in other cortical, subcortical, and cerebellar areas. Our
      findings may suggest the need to further investigate the roles of inflammatory
      reactions and glial activation as potential underlying mechanisms of these
      structural changes.

PMID- 29320501
TI  - Uncertainty of future projections of species distributions in mountainous
      regions.
AB  - Multiple factors introduce uncertainty into projections of species distributions
      under climate change. The uncertainty introduced by the choice of baseline
      climate information used to calibrate a species distribution model and to
      downscale global climate model (GCM) simulations to a finer spatial resolution is
      a particular concern for mountainous regions, as the spatial resolution of
      climate observing networks is often insufficient to detect the steep climatic
      gradients in these areas. Using the maximum entropy (MaxEnt) modeling framework
      together with occurrence data on 21 understory bamboo species distributed across
      the mountainous geographic range of the Giant Panda, we examined the differences
      in projected species distributions obtained from two contrasting sources of
      baseline climate information, one derived from spatial interpolation of coarse
      scale station observations and the other derived from fine-spatial resolution
      satellite measurements. For each bamboo species, the MaxEnt model was calibrated
      separately for the two datasets and applied to 17 GCM simulations downscaled
      using the delta method. Greater differences in the projected spatial
      distributions of the bamboo species were observed for the models calibrated using
      the different baseline datasets than between the different downscaled GCM
      simulations for the same calibration. In terms of the projected future
      climatically-suitable area by species, quantification using a multi-factor
      analysis of variance suggested that the sum of the variance explained by the
      baseline climate dataset used for model calibration and the interaction between
      the baseline climate data and the GCM simulation via downscaling accounted for,
      on average, 40% of the total variation among the future projections. Our analyses
      illustrate that the combined use of gridded datasets developed from station
      observations and satellite measurements can help estimate the uncertainty
      introduced by the choice of baseline climate information to the projected changes
      in species distribution.

PMID- 29320502
TI  - Impaired IFN-alpha-mediated signal in dendritic cells differentiates active from
      latent tuberculosis.
AB  - Individuals exposed to Mycobacterium tuberculosis (Mtb) may be infected and
      remain for the entire life in this condition defined as latent tuberculosis
      infection (LTBI) or develop active tuberculosis (TB). Among the multiple factors
      governing the outcome of the infection, dendritic cells (DCs) play a major role
      in dictating antibacterial immunity. However, current knowledge on the role of
      the diverse components of human DCs in shaping specific T-cell response during
      Mtb infection is limited. In this study, we performed a comparative evaluation of
      peripheral blood circulating DC subsets as well as of monocyte-derived Interferon
      alpha DCs (IFN-DCs) from patients with active TB, subjects with LTBI and healthy
      donors (HD). The proportion of circulating myeloid BDCA3+ DCs (mDC2) and
      plasmacytoid CD123+ DCs (pDCs) declined significantly in active TB patients
      compared to HD, whereas the same subsets displayed a remarkable activation in
      LTBI subjects. Simultaneously, the differentiation of IFN-DCs from active TB
      patients resulted profoundly impaired compared to those from LTBI and HD
      individuals. Importantly, the altered developmental trait of IFN-DCs from active
      TB patients was associated with down-modulation of IFN-linked genes, marked
      changes in molecular signaling conveying antigen (Ag) presentation and full
      inability to induce Ag-specific T cell response. Thus, these data reveal an
      important role of IFN-alpha in determining the induction of Mtb-specific
      immunity.

PMID- 29320503
TI  - Pattern of peripapillary capillary density loss in ischemic optic neuropathy
      compared to that in primary open-angle glaucoma.
AB  - PURPOSE: Both non-arteritic anterior ischemic optic neuropathy (NAION) and
      primary open-angle glaucoma (POAG) damage retinal ganglion cell axons, which are
      perfused by the radial peripapillary capillaries. To evaluate the pattern of
      ischemia, we compared peripapillary capillary density (PCD) in NAION eyes to POAG
      eyes matched for visual field mean deviation and retinal nerve fiber layer
      thickness. METHODS: 31 chronic NAION (>6 months after the acute event) and
      unaffected fellow eyes (31 subjects), 42 moderate and severe POAG eyes (27
      subjects), and 77 control eyes (46 healthy subjects) were imaged with a
      commercial optical coherence tomography angiography system (AngioVue, Avanti
      RTVue-XR, Optovue, CA) at two academic institutions. Two concentric circles of
      diameters 1.95mm (inner) and 3.45mm (outer) were manually placed on images
      centered on the optic nerve head, producing an annular region-of-interest. Image
      analysis with major vessel removal was performed using a custom program. Whole
      image, whole-annulus, and sectoral PCDs were measured. RESULTS: Whole-image and
      whole-annulus PCDs in NAION and moderate and severe POAG eyes were significantly
      decreased compared to unaffected fellow eyes and control eyes (all P<0.001).
      Superior and temporal PCD values were affected more than other sectors in both
      NAION and POAG groups compared to control group. Whole-image and whole-annulus
      PCDs were not statistically different between NAION and POAG eyes (both P =
      0.99). However, of all peripapillary sectors, the inferior sector PCD value was
      less affected in POAG eyes compared to NAION eyes (P = 0.001). Univariate
      analysis results also revealed a significant positive correlation between
      superior and inferior PCDs and corresponding RNFL thicknesses. The inferior
      sector correlation was greater in POAG than NAION eyes. CONCLUSION: While the
      whole PCD values were not different in chronic NAION and POAG, the greater
      correlation of inferior PCD with corresponding RNFL sectors in POAG compared to
      NAION suggests greater susceptibility of the inferior radial peripapillary
      capillary in the pathogenesis of POAG.

PMID- 29320504
TI  - Evaluation of the practicability and virological performance of finger-stick
      whole-blood HIV self-testing in French-speaking sub-Saharan Africa.
AB  - BACKGROUND: Opportunities for HIV testing could be enhanced by offering HIV self
      testing (HIVST) in populations that fear stigma and discrimination when accessing
      conventional HIV counselling and testing in health care facilities. Field
      experience with HIVST has not yet been reported in French-speaking African
      countries. METHODS: The practicability of HIVST was assessed using the prototype
      the Exacto(r) Test HIV (Biosynex, Strasbourg, France) self-test in 322 adults
      living in Kisangani and Bunia, Democratic Republic of the Congo, according to
      World Health Organization's recommendations. Simplified and easy-to-read leaflet
      was translated in French, Lingala and Swahili. RESULTS: Forty-nine percent of
      participants read the instructions for use in French, while 17.1% and 33.9% read
      the instructions in Lingala and Swahili, respectively. The instructions for use
      were correctly understood in 79.5% of cases. The majority (98.4%) correctly
      performed the HIV self-test; however, 20.8% asked for oral assistance. Most of
      the participants (95.3%) found that performing the self-test was easy, while 4.7%
      found it difficult. Overall, the results were correctly interpreted in 90.2% of
      cases. Among the positive, negative, and invalid self-tests, misinterpretation
      occurred in 6.5%, 11.2%, and 16.0% of cases, respectively (P<0.0001). The Cohen's
      kappa coefficient was 0.84. The main obstacle for HIVST was educational level,
      with execution and interpretation difficulties occurring among poorly educated
      people. The Exacto(r) Test HIV self-test showed 100.0% (95% CI; 98.8-100.0)
      sensitivity and 99.2% (95% CI; 97.5-99.8) specificity. CONCLUSIONS: Our field
      observations demonstrate: (i) the need to adapt the instructions for use to the
      Congolese general public, including adding educational pictograms as well as
      instructions for use in the local vernacular language(s); (ii) frequent
      difficulties understanding the instructions for use in addition to frequent
      misinterpretation of test results; and (iii) the generally good practicability of
      the HIV self-test despite some limitations. Supervised use of HIVST is
      recommended among poorly-educated people.

PMID- 29320505
TI  - Methodology of mixed load customized bus lines and adjustment based on time
      windows.
AB  - Custom bus routes need to be optimized to meet the needs of a customized bus for
      personalized trips of different passengers. This paper introduced a customized
      bus routing problem in which trips for each depot are given, and each bus stop
      has a fixed time window within which trips should be completed. Treating a trip
      as a virtual stop was the first consideration in solving the school bus routing
      problem (SBRP). Then, the mixed load custom bus routing model was established
      with a time window that satisfies its requirement and the result were solved by
      Cplex software. Finally, a simple network diagram with three depots, four pickup
      stops, and five delivery stops was structured to verify the correctness of the
      model, and based on the actual example, the result is that all the buses ran
      124.42 kilometers, the sum of kilometers was 10.35 kilometers less than before.
      The paths and departure times of the different busses that were provided by the
      model were evaluated to meet the needs of the given conditions, thus providing
      valuable information for actual work.

PMID- 29320506
TI  - Thinking of me: Self-focus reduces sharing and helping in seven- to eight-year
      olds.
AB  - By 7-to 8-years of age, most children readily adhere to prosocial norms aimed at
      benefiting others through giving up time and effort (helping) or resources
      (sharing). Two studies explored whether sharing and helping by 7-to 8-year olds
      (N = 180) could be influenced by priming children's attention on themselves or
      their friends through a semi-structured interview. Results revealed that self
      priming led to reductions in both sharing and helping compared to friendship
      priming or a control condition. These findings are considered as indicative of
      the fragile state of prosocial behaviours at this age that can be easily shifted
      towards more selfish biases by simple priming.

PMID- 29320507
TI  - HPV prevalence and HPV-related dysplasia in elderly women.
AB  - INTRODUCTION: In Sweden, where screening ends at the age of 60, about 30% of the
      cervical cancer cases occur in women older than 60. The aim of the present study
      was to investigate the prevalence of HPV and cervical dysplasia in women of 60
      years and above. PATIENTS AND METHODS: From September 2013 until June 2015, 1051
      women aged 60-89 years (mean 68 years) were sampled for an HPV test when
      attending an outpatient gynecology clinic. Women with positive results had a
      second HPV test and liquid based cytology (LBC), after 3.5 months on average.
      Those with a positive second HPV test were examined by colposcopy, and biopsy and
      a sample for LBC was obtained. RESULTS: The prevalence of HPV was 4.1%, (95%CI
      3.0-5.5, n = 43) at the first test, and at the second test 2.6% remained positive
      (95%CI 1.7-3.8, n = 27). The majority of women positive in both HPV tests, had
      dysplasia in histology, 81.5% (22/27) (4 CIN 2-0.4%, 18 CIN 1-1.7%). HPV-related
      dysplasia was found in 2.1%, (95%CI 1.3-3.2, n = 22) of the 1051 women. Four of
      the 22 women with positive HPV tests also had abnormal cytology, one ASCUS and
      three CIN 1. No cancer or glandular dysplasia was detected. CONCLUSION: A
      significant proportion of elderly women were found to have a persistent cervical
      HPV infection. Among them there was a high prevalence of CIN diagnosed by
      histology. The HPV test showed high sensitivity and specificity in detecting CIN
      in elderly women, while cytology showed extremely low sensitivity.

PMID- 29320508
TI  - Characterizing the field of Atomic Layer Deposition: Authors, topics, and
      collaborations.
AB  - This paper describes how Atomic Layer Deposition (ALD) has evolved over time
      using a combination of bibliometric, social network, and text analysis. We
      examined the rate of knowledge production as well as changes in authors,
      journals, and collaborators, showing a steady growth of ALD research. The study
      of the collaboration network of ALD scientists over time points out that the ALD
      research community is becoming larger and more interconnected, with a largest
      connected component that spans 90% of the authors in 2015. In addition, the
      evolution of network centrality measures (degree and betweenness centrality) and
      author productivity revealed the central figures in ALD over time, including new
      "stars" appearing in the last decade. Finally, the study of the title words in
      our dataset is consistent with a shift in focus on research topics towards energy
      applications and nanotechnology.

PMID- 29320509
TI  - Dynamics of co-authorship and productivity across different fields of scientific
      research.
AB  - We aimed to assess which factors correlate with collaborative behavior and
      whether such behavior associates with scientific impact (citations and becoming a
      principal investigator). We used the R index which is defined for each author as
      log(Np)/log(I1), where I1 is the number of co-authors who appear in at least I1
      papers written by that author and Np are his/her total papers. Higher R means
      lower collaborative behavior, i.e. not working much with others, or not
      collaborating repeatedly with the same co-authors. Across 249,054 researchers who
      had published >=30 papers in 2000-2015 but had not published anything before
      2000, R varied across scientific fields. Lower values of R (more collaboration)
      were seen in physics, medicine, infectious disease and brain sciences and higher
      values of R were seen for social science, computer science and engineering. Among
      the 9,314 most productive researchers already reaching Np >= 30 and I1 >= 4 by
      the end of 2006, R mostly remained stable for most fields from 2006 to 2015 with
      small increases seen in physics, chemistry, and medicine. Both US-based
      authorship and male gender were associated with higher values of R (lower
      collaboration), although the effect was small. Lower values of R (more
      collaboration) were associated with higher citation impact (h-index), and the
      effect was stronger in certain fields (physics, medicine, engineering, health
      sciences) than in others (brain sciences, computer science, infectious disease,
      chemistry). Finally, for a subset of 400 U.S. researchers in medicine, infectious
      disease and brain sciences, higher R (lower collaboration) was associated with a
      higher chance of being a principal investigator by 2016. Our analysis maps the
      patterns and evolution of collaborative behavior across scientific disciplines.

PMID- 29320512
TI  - Killing wolves to prevent predation on livestock may protect one farm but harm
      neighbors.
AB  - Large carnivores, such as gray wolves, Canis lupus, are difficult to protect in
      mixed-use landscapes because some people perceive them as dangerous and because
      they sometimes threaten human property and safety. Governments may respond by
      killing carnivores in an effort to prevent repeated conflicts or threats,
      although the functional effectiveness of lethal methods has long been questioned.
      We evaluated two methods of government intervention following independent events
      of verified wolf predation on domestic animals (depredation) in the Upper
      Peninsula of Michigan, USA between 1998-2014, at three spatial scales. We
      evaluated two intervention methods using log-rank tests and conditional Cox
      recurrent event, gap time models based on retrospective analyses of the following
      quasi-experimental treatments: (1) selective killing of wolves by trapping near
      sites of verified depredation, and (2) advice to owners and haphazard use of non
      lethal methods without wolf-killing. The government did not randomly assign
      treatments and used a pseudo-control (no removal of wolves was not a true
      control), but the federal permission to intervene lethally was granted and
      rescinded independent of events on the ground. Hazard ratios suggest lethal
      intervention was associated with an insignificant 27% lower risk of recurrence of
      events at trapping sites, but offset by an insignificant 22% increase in risk of
      recurrence at sites up to 5.42 km distant in the same year, compared to the non
      lethal treatment. Our results do not support the hypothesis that Michigan's use
      of lethal intervention after wolf depredations was effective for reducing the
      future risk of recurrence in the vicinities of trapping sites. Examining only the
      sites of intervention is incomplete because neighbors near trapping sites may
      suffer the recurrence of depredations. We propose two new hypotheses for
      perceived effectiveness of lethal methods: (a) killing predators may be perceived
      as effective because of the benefits to a small minority of farmers, and (b) if
      neighbors experience side-effects of lethal intervention such as displaced
      depredations, they may perceive the problem growing and then demand more lethal
      intervention rather than detecting problems spreading from the first trapping
      site. Ethical wildlife management guided by the "best scientific and commercial
      data available" would suggest suspending the standard method of trapping wolves
      in favor of non-lethal methods (livestock guarding dogs or fladry) that have been
      proven effective in preventing livestock losses in Michigan and elsewhere.

PMID- 29320510
TI  - Adipose tissue ATGL modifies the cardiac lipidome in pressure-overload-induced
      left ventricular failure.
AB  - Adipose tissue lipolysis occurs during the development of heart failure as a
      consequence of chronic adrenergic stimulation. However, the impact of enhanced
      adipose triacylglycerol hydrolysis mediated by adipose triglyceride lipase (ATGL)
      on cardiac function is unclear. To investigate the role of adipose tissue
      lipolysis during heart failure, we generated mice with tissue-specific deletion
      of ATGL (atATGL-KO). atATGL-KO mice were subjected to transverse aortic
      constriction (TAC) to induce pressure-mediated cardiac failure. The cardiac mouse
      lipidome and the human plasma lipidome from healthy controls (n = 10) and
      patients with systolic heart failure (HFrEF, n = 13) were analyzed by MS-based
      shotgun lipidomics. TAC-induced increases in left ventricular mass (LVM) and
      diastolic LV inner diameter were significantly attenuated in atATGL-KO mice
      compared to wild type (wt) -mice. More importantly, atATGL-KO mice were protected
      against TAC-induced systolic LV failure. Perturbation of lipolysis in the adipose
      tissue of atATGL-KO mice resulted in the prevention of the major cardiac lipidome
      changes observed after TAC in wt-mice. Profound changes occurred in the lipid
      class of phosphatidylethanolamines (PE) in which multiple PE-species were
      markedly induced in failing wt-hearts, which was attenuated in atATGL-KO hearts.
      Moreover, selected heart failure-induced PE species in mouse hearts were also
      induced in plasma samples from patients with chronic heart failure. TAC-induced
      cardiac PE induction resulted in decreased PC/ PE-species ratios associated with
      increased apoptotic marker expression in failing wt-hearts, a process absent in
      atATGL-KO hearts. Perturbation of adipose tissue lipolysis by ATGL-deficiency
      ameliorated pressure-induced heart failure and the potentially deleterious
      cardiac lipidome changes that accompany this pathological process, namely the
      induction of specific PE species. Non-cardiac ATGL-mediated modulation of the
      cardiac lipidome may play an important role in the pathogenesis of chronic heart
      failure.

PMID- 29320511
TI  - Application of a phenotypic drug discovery strategy to identify biological and
      chemical starting points for inhibition of TSLP production in lung epithelial
      cells.
AB  - Thymic stromal lymphopoietin (TSLP) is a cytokine released by human lung
      epithelium in response to external insult. Considered as a master switch in T
      helper 2 lymphocyte (Th2) mediated responses, TSLP is believed to play a key role
      in allergic diseases including asthma. The aim of this study was to use a
      phenotypic approach to identify new biological and chemical starting points for
      inhibition of TSLP production in human bronchial epithelial cells (NHBE), with
      the objective of reducing Th2-mediated airway inflammation. To this end, a
      phenotypic screen was performed using poly I:C / IL-4 stimulated NHBE cells
      interrogated with a 44,974 compound library. As a result, 85 hits which
      downregulated TSLP protein and mRNA levels were identified and a representative
      subset of 7 hits was selected for further characterization. These molecules
      inhibited the activity of several members of the MAPK, PI3K and tyrosine kinase
      families and some of them have been reported as modulators of cellular phenotypic
      endpoints like cell-cell contacts, microtubule polymerization and caspase
      activation. Characterization of the biological profile of the hits suggested that
      mTOR could be a key activity involved in the regulation of TSLP production in
      NHBE cells. Among other targeted kinases, inhibition of p38 MAPK and JAK kinases
      showed different degrees of correlation with TSLP downregulation, while Syk
      kinase did not seem to be related. Overall, inhibition of TSLP production by the
      selected hits, rather than resulting from inhibition of single isolated targets,
      appeared to be due to a combination of activities with different levels of
      relevance. Finally, a hit expansion exercise yielded additional active compounds
      that could be amenable to further optimization, providing an opportunity to
      dissociate TSLP inhibition from other non-desired activities. This study
      illustrates the potential of phenotypic drug discovery to complement target based
      approaches by providing new chemistry and biology leads.

PMID- 29320513
TI  - A harm-reduction model of abortion counseling about misoprostol use in Peru with
      telephone and in-person follow-up: A cohort study.
AB  - BACKGROUND: In Peru, abortion is legal only to preserve the life and health of
      the woman. A non-profit clinic system in Peru implemented a harm-reduction model
      for women with unwanted pregnancy that included pre-abortion care with
      instructions about misoprostol use and post-abortion care; they started offering
      telephone follow-up for clients in 2011. This study aimed to evaluate the
      effectiveness and safety of the harm-reduction model, and to compare outcomes by
      type of follow-up obtained. METHODS: Between January 2012 and March 2013, 500
      adult women seeking harm-reduction services were recruited into the study.
      Telephone surveys were conducted approximately four weeks after their initial
      harm-reduction counseling session with 262 women (response rate 52%); 9
      participants were excluded. The survey focused on whether women pursued an
      abortion, and if so, what their experience was. Demographic and clinical data
      were also extracted from clinic records. RESULTS: Eighty-six percent of
      participants took misoprostol; among those taking misoprostol, 89% reported a
      complete abortion at the time of the survey. Twenty-two percent obtained an
      aspiration after taking misoprostol and 8% self-reported adverse events including
      hemorrhage without transfusion, infection, or severe pain. Among women who took
      misoprostol, 46% reported receiving in-person follow-up (in some cases both
      telephone and in-person), 34% received telephone only, and 20% did not report
      receiving any form of follow-up. Those who had in-person follow-up with the
      counselor were most likely to report a complete abortion (<0.001). Satisfaction
      with both types of follow-up was very high, with 81%-89% reporting being very
      satisfied. CONCLUSIONS: Liberalization of restrictive abortion laws is associated
      with improvements in health outcomes, but the process of legal reform is often
      lengthy. In the interim, giving women information about evidence-based regimens
      of misoprostol, as well as offering a range of follow-up options to ensure high
      quality post-abortion care, may reduce the risks associated with unsafe abortion.

PMID- 29320514
TI  - Sound-mapping a coniferous forest-Perspectives for biodiversity monitoring and
      noise mitigation.
AB  - Acoustic diversity indices have been proposed as low-cost biodiversity monitoring
      tools. The acoustic diversity of a soundscape can be indicative of the richness
      of an acoustic community and the structural/vegetation characteristics of a
      habitat. There is a need to apply these methods to landscapes that are
      ecologically and/or economically important. We investigate the relationship
      between the acoustic properties of a coniferous forest with stand-age and
      structure. We sampled a 73 point grid in part of the UK's largest man-made
      lowland coniferous plantation forest, covering a 320ha mosaic of different aged
      stands. Forest stands ranged from 0-85 years old providing an age-gradient. Short
      soundscape recordings were collected from each grid point on multiple mornings
      (between 6am-11am) to capture the dawn chorus. We repeated the study during
      July/August in 2014 and again in 2015. Five acoustic indices were calculated for
      a total of 889 two minute samples. Moderate relationships between acoustic
      diversity with forest stand-age and vegetation characteristics (canopy height;
      canopy cover) were observed. Ordinations suggest that as structural complexity
      and forest age increases, the higher frequency bands (4-10KHz) become more
      represented in the soundscape. A strong linear relationship was observed between
      distance to the nearest road and the ratio of anthropogenic noise to biological
      sounds within the soundscape. Similar acoustic patterns were observed in both
      years, though acoustic diversity was generally lower in 2014, which was likely
      due to differences in wind conditions between years. Our results suggest that
      developing these relatively low-cost acoustic monitoring methods to inform
      adaptive management of production landscapes, may lead to improved biodiversity
      monitoring. The methods may also prove useful for modelling road noise, landscape
      planning and noise mitigation.

PMID- 29320515
TI  - Vigilant conservatism in evaluating communicated information.
AB  - In the absence of other information, people put more weight on their own opinion
      than on the opinion of others: they are conservative. Several proximal mechanisms
      have been suggested to account for this finding. One of these mechanisms is that
      people cannot access reasons for other people's opinions, but they can access the
      reasons for their own opinions-whether they are the actual reasons that led them
      to hold the opinions (rational access to reasons), or post-hoc constructions
      (biased access to reasons). In four experiments, participants were asked to
      provide an opinion, and then faced with another participant's opinion and asked
      if they wanted to revise their initial opinion. Some questions were manipulated
      so that the advice participants were receiving was in fact their own opinion,
      while what they thought was their own opinion was in fact not. In all
      experiments, the participants were consistently biased towards what they thought
      was their own opinion, showing that conservativeness cannot be explained by
      rational access to reasons, which should have favored the advice. One experiment
      revealed that conservativeness was not decreased under time pressure, suggesting
      that biased access to reasons is an unlikely explanation for conservativeness.
      The experiments also suggest that repetition plays a role in advice taking, with
      repeated opinions being granted more weight than non-fluent opinions. Our results
      are not consistent with any of the established proximal explanations for
      conservatism. Instead, we suggest an ultimate explanation-vigilant conservatism
      that sees conservatism as adaptive since receivers should be wary of senders'
      interests, as they rarely perfectly converge with theirs.

PMID- 29320516
TI  - Impact of mode of delivery on pregnancy outcomes in women with premature rupture
      of membranes after 28 weeks of gestation in a low-resource setting: A prospective
      cohort study.
AB  - BACKGROUND: Despite the high prevalence of premature rupture of membranes (PROM)
      in low-resource settings, the preferred mode of delivery remains unclear. We
      compared the perinatal mortality in a prospective cohort of women with PROM after
      28 weeks following vaginal or caesarean delivery at Mulago Hospital with the aim
      of adopting evidence based practice and improving patient care. METHODS: Between
      November 2015 and May 2016, 1455 women with PROM after 28 weeks of gestation and
      their newborns were prospectively followed from admission to discharge at Mulago
      Hospital. The primary outcome was perinatal mortality. Secondary neonatal
      outcomes included sepsis and admission to the Special Care Unit. Maternal
      outcomes included maternal deaths and complications. Outcomes were compared
      between women who had vaginal vs. caesarean delivery using multivariable logistic
      regression. All statistical tests were 2-sided with the level of statistical
      significance set at p < 0.05. RESULTS: The incidence of PROM was 12.1%. The
      perinatal mortality following PROM was 65 per 1000 live births. Of the 1425 women
      with PROM, 991 (69.5%) had vaginal delivery and 434 (30.5%) underwent Caesarean
      section. There was no statistical difference in perinatal mortality by the mode
      of delivery (vaginal vs. caesarean) in PROM (p = 0.12). The risk factors for
      perinatal mortality included chorioamnionitis, failure to administer
      corticosteroids in preterm PROM, gestational age (28-33 weeks), duration of
      drainage of liquor (24-48 hours), and presence of maternal complications.
      Caesarean delivery was associated with increased maternal postpartum infections,
      admission to the Special Care Unit and maternal death. CONCLUSION: In low
      resource settings, vaginal delivery is the preferred mode of delivery for PROM
      after 28 weeks gestation. It is associated with lesser maternal and perinatal
      morbidity when compared to caesarean delivery.

PMID- 29320517
TI  - Explaining the decline in coronary heart disease mortality rates in the Slovak
      Republic between 1993-2008.
AB  - OBJECTIVE: Between the years 1993 and 2008, mortality rates from coronary heart
      disease (CHD) in the Slovak Republic have decreased by almost one quarter.
      However, this was a smaller decline than in neighbouring countries. The aim of
      this modelling study was therefore to quantify the contributions of risk factor
      changes and the use of evidence-based medical therapies to the CHD mortality
      decline between 1993 and 2008. METHODS: We identified, obtained and scrutinised
      the data required for the model. These data detailed trends in the major
      population cardiovascular risk factors (smoking, blood pressure, total
      cholesterol, diabetes prevalence, body mass index (BMI) and physical activity
      levels), and also the uptake of all standard CHD treatments. The main data
      sources were official statistics (National Health Information Centre and
      Statistical Office of the Slovak Republic) and national representative studies
      (AUDIT, SLOVAKS, SLOVASeZ, CINDI, EHES, EHIS). The previously validated IMPACT
      policy model was then used to combine and integrate these data with effect sizes
      from published meta-analyses quantifying the effectiveness of specific evidence
      based treatments, and population-wide changes in cardiovascular risk factors.
      Results were expressed as deaths prevented or postponed (DPPs) attributable to
      risk factor changes or treatments. Uncertainties were explored using sensitivity
      analyses. RESULTS: Between 1993 and 2008 age-adjusted CHD mortality rates in the
      Slovak Republic (SR) decreased by 23% in men and 26% in women aged 25-74 years.
      This represented some 1820 fewer CHD deaths in 2008 than expected if mortality
      rates had not fallen. The IMPACT model explained 91% of this mortality decline.
      Approximately 50% of the decline was attributable to changes in acute phase and
      secondary prevention treatments, particularly acute and chronic treatments for
      heart failure (~12%), acute coronary syndrome treatments (~9%) and secondary
      prevention following AMI and revascularisation (~8%). Changes in CHD risk factors
      explained approximately 41% of the total mortality decrease, mainly reflecting
      reductions in total serum cholesterol. However, other risk factors demonstrated
      adverse trends and thus generated approximately 740 additional deaths.
      CONCLUSION: Our analysis suggests that approximately half the CHD mortality fall
      recently observed in the SR may be attributable to the increased use of evidence
      based treatments. However, the adverse trends observed in all the major
      cardiovascular risk factors (apart from total cholesterol) are deeply worrying.
      They highlight the need for more energetic population-wide prevention policies
      such as tobacco control, reducing salt and industrial trans fats content in
      processed food, clearer food labelling and regulated marketing of processed foods
      and sugary drinks.

PMID- 29320519
TI  - The effect of small-sided games with different levels of opposition on the
      tactical behaviour of young footballers with different levels of sport expertise.
AB  - To optimize players' tactical abilities, coaches need to design training sessions
      with representative learning tasks, such as, small-sided games. Moreover, it is
      necessary to adapt the complexity of the tasks to the skill level of the athletes
      to maximally improve their perceptual, visual and attentive abilities. The
      objective of this study was to analyze the effect of two teaching programs, each
      utilizing modified games with varied levels of opposition, on decision-making and
      action execution in young players with different levels of sports expertise. 19
      football players (U12), separated into two ability groups (Average versus Low
      skill-level), participated in a series of training sessions that were spread over
      4 phases: Pre-intervention 1, Intervention 1 (teaching program based on modified
      games with numerical superiority in attack), Pre-intervention 2 and Intervention
      2 (teaching program based on modified games with numerical equality). Each
      intervention phase lasted 14 sessions. Decision-making and the execution of pass
      action during league matches over the same period were evaluated using the Game
      Performance Evaluation Tool (GPET). The Average skill-level group showed
      significant differences after the first intervention in decision-making and
      execution of the pass action (decision-making, p = .015; execution, p = .031),
      but not after the second intervention (decision-making, p = 1.000; execution, p =
      1.000). For the Low skill-level group, significant differences were only observed
      in the execution of passing between the first and last phases (p = .014). These
      findings seem to indicate that for groups with an average level of expertise,
      training with numerical superiority in attack provides players with more time to
      make better decisions and to better execute actions. However, for lower-level
      groups programs may take longer to facilitate improvement. Nevertheless,
      numerical equality did not result in improvement for either group.

PMID- 29320518
TI  - Increased mitochondrial DNA diversity in ancient Columbia River basin Chinook
      salmon Oncorhynchus tshawytscha.
AB  - The Columbia River and its tributaries provide essential spawning and rearing
      habitat for many salmonid species, including Chinook salmon (Oncorhynchus
      tshawytscha). Chinook salmon were historically abundant throughout the basin and
      Native Americans in the region relied heavily on these fish for thousands of
      years. Following the arrival of Europeans in the 1800s, salmon in the basin
      experienced broad declines linked to overfishing, water diversion projects,
      habitat destruction, connectivity reduction, introgression with hatchery-origin
      fish, and hydropower development. Despite historical abundance, many native
      salmonids are now at risk of extinction. Research and management related to
      Chinook salmon is usually explored under what are termed "the four H's": habitat,
      harvest, hatcheries, and hydropower; here we explore a fifth H, history. Patterns
      of prehistoric and contemporary mitochondrial DNA variation from Chinook salmon
      were analyzed to characterize and compare population genetic diversity prior to
      recent alterations and, thus, elucidate a deeper history for this species. A
      total of 346 ancient and 366 contemporary samples were processed during this
      study. Species was determined for 130 of the ancient samples and control region
      haplotypes of 84 of these were sequenced. Diversity estimates from these 84
      ancient Chinook salmon were compared to 379 contemporary samples. Our analysis
      provides the first direct measure of reduced genetic diversity for Chinook salmon
      from the ancient to the contemporary period, as measured both in direct loss of
      mitochondrial haplotypes and reductions in haplotype and nucleotide diversity.
      However, these losses do not appear equal across the basin, with higher losses of
      diversity in the mid-Columbia than in the Snake subbasin. The results are
      unexpected, as the two groups were predicted to share a common history as parts
      of the larger Columbia River Basin, and instead indicate that Chinook salmon in
      these subbasins may have divergent demographic histories.

PMID- 29320520
TI  - Not seeing the grass for the trees: Timber plantations and agriculture shrink
      tropical montane grassland by two-thirds over four decades in the Palani Hills, a
      Western Ghats Sky Island.
AB  - Tropical montane habitats, grasslands, in particular, merit urgent conservation
      attention owing to the disproportionate levels of endemic biodiversity they
      harbour, the ecosystem services they provide, and the fact that they are among
      the most threatened habitats globally. The Shola Sky Islands in the Western Ghats
      host a matrix of native forest-grassland matrix that has been planted over the
      last century, with exotic timber plantations. The popular discourse on the
      landscape change is that mainly forests have been lost to the timber plantations
      and recent court directives are to restore Shola forest trees. In this study, we
      examine spatiotemporal patterns of landscape change over the last 40 years in the
      Palani Hills, a significant part of the montane habitat in the Western Ghats.
      Using satellite imagery and field surveys, we find that 66% of native grasslands
      and 31% of native forests have been lost over the last 40 years. Grasslands have
      gone from being the dominant, most contiguous land cover to one of the rarest and
      most fragmented. They have been replaced by timber plantations and, to a lesser
      extent, expanding agriculture. We find that the spatial pattern of grassland loss
      to plantations differs from the loss to agriculture, likely driven by the
      invasion of plantation species into grasslands. We identify remnant grasslands
      that should be prioritised for conservation and make specific recommendations for
      conservation and restoration of grasslands in light of current management policy
      in the Palani Hills, which favours large-scale removal of plantations and
      emphasises the restoration of native forests.

PMID- 29320521
TI  - CD8+ T cell infiltration in breast and colon cancer: A histologic and statistical
      analysis.
AB  - The prevalence of cytotoxic tumor infiltrating lymphocytes (TILs) has
      demonstrated prognostic value in multiple tumor types. In particular, CD8 counts
      (in combination with CD3 and CD45RO) have been shown to be superior to
      traditional UICC staging in colon cancer patients and higher total CD8 counts
      have been associated with better survival in breast cancer patients. However,
      immune infiltrate heterogeneity can lead to potentially significant
      misrepresentations of marker prevalence in routine histologic sections. We
      examined step sections of breast and colorectal cancer samples for CD8+ T cell
      prevalence by standard chromogenic immunohistochemistry to determine marker
      variability and inform practice of T cell biomarker assessment in formalin-fixed,
      paraffin-embedded (FFPE) tissue samples. Stained sections were digitally imaged
      and CD8+ lymphocytes within defined regions of interest (ROI) including the tumor
      and surrounding stroma were enumerated. Statistical analyses of CD8+ cell count
      variability using a linear model/ANOVA framework between patients as well as
      between levels within a patient sample were performed. Our results show that CD8+
      T-cell distribution is highly homogeneous within a standard tissue sample in both
      colorectal and breast carcinomas. As such, cytotoxic T cell prevalence by
      immunohistochemistry on a single level or even from a subsample of biopsy
      fragments taken from that level can be considered representative of cytotoxic T
      cell infiltration for the entire tumor section within the block. These findings
      support the technical validity of biomarker strategies relying on CD8
      immunohistochemistry.

PMID- 29320522
TI  - Do systematic reviews address community healthcare professionals' wound care
      uncertainties? Results from evidence mapping in wound care.
AB  - BACKGROUND: Complex wounds such as leg and foot ulcers are common, resource
      intensive and have negative impacts on patients' wellbeing. Evidence-based
      decision-making, substantiated by high quality evidence such as from systematic
      reviews, is widely advocated for improving patient care and healthcare
      efficiency. Consequently, we set out to classify and map the extent to which up
      to-date systematic reviews containing robust evidence exist for wound care
      uncertainties prioritised by community-based healthcare professionals. METHODS:
      We asked healthcare professionals to prioritise uncertainties based on complex
      wound care decisions, and then classified 28 uncertainties according to the type
      and level of decision. For each uncertainty, we searched for relevant systematic
      reviews. Two independent reviewers screened abstracts and full texts of reviews
      against the following criteria: meeting an a priori definition of a systematic
      review, sufficiently addressing the uncertainty, published during or after 2012,
      and identifying high quality research evidence. RESULTS: The most common
      uncertainty type was 'interventions' 24/28 (85%); the majority concerned wound
      level decisions 15/28 (53%) however, service delivery level decisions (10/28)
      were given highest priority. Overall, we found 162 potentially relevant reviews
      of which 57 (35%) were not systematic reviews. Of 106 systematic reviews, only 28
      were relevant to an uncertainty and 18 of these were published within the
      preceding five years; none identified high quality research evidence.
      CONCLUSIONS: Despite the growing volume of published primary research, healthcare
      professionals delivering wound care have important clinical uncertainties which
      are not addressed by up-to-date systematic reviews containing high certainty
      evidence. These are high priority topics requiring new research and systematic
      reviews which are regularly updated. To reduce clinical and research waste, we
      recommend systematic reviewers and researchers make greater efforts to ensure
      that research addresses important clinical uncertainties and is of sufficient
      rigour to inform practice.

PMID- 29320523
TI  - Risk of pancreatitis after pancreatic duct guidewire placement during endoscopic
      retrograde cholangiopancreatography.
AB  - BACKGROUND & AIMS: Advanced techniques have been developed to overcome difficult
      cannulation cases in endoscopic retrograde cholangiopancreatography (ERCP).
      Pancreatic duct guidewire placement method (PGW) is performed in difficult
      cannulation cases; it is possible that it places patients at risk of post-ERCP
      pancreatitis (PEP). The mechanism of PEP is still unclear, but pancreatic duct
      pressure and injury of pancreatic duct are known causes of PEP. Therefore, we
      hypothesized a relationship between pancreatic duct diameter and PEP and
      predicted that PGW would increase the risk of PEP in patients with non-dilated
      pancreatic ducts. This study aimed to investigate whether PGW increased the risk
      of PEP in patients with pancreatic duct diameter <= 3 mm. METHODS: We analyzed
      332 patients with pancreatic duct <= 3 mm who performed first time ERCP session.
      The primary endpoint was the rate of adverse event of PEP. We evaluated the risk
      of PEP in patients who had undergone PGW compared to those who had not, using the
      inverse probability of treatment weighting (IPTW) analysis. RESULTS: PGW was
      found to be an independent risk factor for PEP by univariate analysis (odds ratio
      [OR], 2.45; 95% confidence interval [CI], 1.12-5.38; p = 0.03) after IPTW in
      patients with pancreatic duct diameter <= 3 mm. Adjusted for all covariates, PGW
      remained an independent risk factor for PEP (OR, 3.12; 95% CI, 1.33-7.33; p =
      0.01). CONCLUSION: Our results indicate that PGW in patients with pancreatic duct
      diameter <= 3 mm increases the risk of PEP.

PMID- 29320524
TI  - Patients with primary biliary cholangitis and fatigue present with depressive
      symptoms and selected cognitive deficits, but with normal attention performance
      and brain structure.
AB  - BACKGROUND: In primary biliary cholangitis (PBC) fatigue is a major clinical
      challenge of unknown etiology. By demonstrating that fatigue in PBC is associated
      with an impaired cognitive performance, previous studies have pointed out the
      possibility of brain abnormalities underlying fatigue in PBC. Whether structural
      brain changes are present in PBC patients with fatigue, however, is unclear. To
      evaluate the role of structural brain abnormalities in PBC patients severely
      affected from fatigue we, therefore, performed a case-control cerebral magnetic
      resonance imaging (cMRI) study and correlated changes of white and grey brain
      matter with the cognitive and attention performance. METHODS: 20 female patients
      with PBC and 20 female age-matched controls were examined in this study. The
      assessment of fatigue, psychological symptoms, cognitive and attention
      performance included clinical questionnaires, established cognition tests and a
      computerized test battery of attention performance. T1-weighted cMRI and
      diffusion tensor imaging (DTI) scans were acquired with a 3 Tesla scanner.
      Structural brain alterations were investigated with voxel-based morphometry (VBM)
      and DTI analyses. Results were correlated to the cognitive and attention
      performance. RESULTS: Compared to healthy controls, PBC patients had
      significantly higher levels of fatigue and associated psychological symptoms.
      Except for an impairment of verbal fluency, no cognitive or attention deficits
      were found in the PBC cohort. The VBM and DTI analyses revealed neither major
      structural brain abnormalities in the PBC cohort nor correlations with the
      cognitive and attention performance. CONCLUSIONS: Despite the high burden of
      fatigue and selected cognitive deficits, the attention performance of PBC
      patients appears to be comparable to healthy people. As structural brain
      alterations do not seem to be present in PBC patients with fatigue, fatigue in
      PBC must be regarded as purely functional. Future studies should evaluate,
      whether functional brain changes underlie fatigue in PBC.

PMID- 29320525
TI  - Seabird parents provision their chick in a coordinated manner.
AB  - Pair collaborative behavior may play an important role in avian reproduction.
      However, evidence for this mainly comes from certain ecological groups (e.g.
      passerines). We studied the coordination of parents in foraging and its effect on
      food provisioning rate and chick growth in a small seabird, the Dovekie (Little
      auk, Alle alle). The species exhibits a dual foraging strategy, where
      provisioning adults make foraging trips of short (mean ~2 h; to provide food for
      the chick) and long duration (mean ~ 13 h; mainly for adults self-maintenance,
      although the food is also brought to the chick). We expected that offspring would
      benefit if parents coordinate their foraging patterns: one making short trips in
      the time when the other performing the long one. We examined this hypothesis
      using Monte Carlo randomization tests on field data collected during observations
      of individually marked birds. We found that parents did indeed adjust
      provisioning, making their long and short trips in an alternating pattern with
      respect to each other. Furthermore, we found that a higher level of coordination
      is associated with a lower variability in the duration of inter-feeding
      intervals, although this does not affect chick growth. Nevertheless, our results
      provide compelling evidence on the coordinated behavior of breeding partners.

PMID- 29320526
TI  - Temporal and spectral characteristics of dynamic functional connectivity between
      resting-state networks reveal information beyond static connectivity.
AB  - Estimation of functional connectivity (FC) has become an increasingly powerful
      tool for investigating healthy and abnormal brain function. Static connectivity,
      in particular, has played a large part in guiding conclusions from the majority
      of resting-state functional MRI studies. However, accumulating evidence points to
      the presence of temporal fluctuations in FC, leading to increasing interest in
      estimating FC as a dynamic quantity. One central issue that has arisen in this
      new view of connectivity is the dramatic increase in complexity caused by dynamic
      functional connectivity (dFC) estimation. To computationally handle this
      increased complexity, a limited set of dFC properties, primarily the mean and
      variance, have generally been considered. Additionally, it remains unclear how to
      integrate the increased information from dFC into pattern recognition techniques
      for subject-level prediction. In this study, we propose an approach to address
      these two issues based on a large number of previously unexplored temporal and
      spectral features of dynamic functional connectivity. A Generalized
      Autoregressive Conditional Heteroskedasticity (GARCH) model is used to estimate
      time-varying patterns of functional connectivity between resting-state networks.
      Time-frequency analysis is then performed on dFC estimates, and a large number of
      previously unexplored temporal and spectral features drawn from signal processing
      literature are extracted for dFC estimates. We apply the investigated features to
      two neurologic populations of interest, healthy controls and patients with
      temporal lobe epilepsy, and show that the proposed approach leads to substantial
      increases in predictive performance compared to both traditional estimates of
      static connectivity as well as current approaches to dFC. Variable importance is
      assessed and shows that there are several quantities that can be extracted from
      dFC signal which are more informative than the traditional mean or variance of
      dFC. This work illuminates many previously unexplored facets of the dynamic
      properties of functional connectivity between resting-state networks, and
      provides a platform for dynamic functional connectivity analysis that facilitates
      its usage as an investigative measure for healthy as well as abnormal brain
      function.

PMID- 29320527
TI  - Transcriptome analysis during ripening of table grape berry cv. Thompson
      Seedless.
AB  - Ripening is one of the key processes associated with the development of major
      organoleptic characteristics of the fruit. This process has been extensively
      characterized in climacteric fruit, in contrast with non-climacteric fruit such
      as grape, where the process is less understood. With the aim of studying changes
      in gene expression during ripening of non-climacteric fruit, an Illumina based
      RNA-Seq transcriptome analysis was performed on four developmental stages,
      between veraison and harvest, on table grapes berries cv Thompson Seedless.
      Functional analysis showed a transcriptional increase in genes related with
      degradation processes of chlorophyll, lipids, macromolecules recycling and
      nucleosomes organization; accompanied by a decrease in genes related with
      chloroplasts integrity and amino acid synthesis pathways. It was possible to
      identify several processes described during leaf senescence, particularly close
      to harvest. Before this point, the results suggest a high transcriptional
      activity associated with the regulation of gene expression, cytoskeletal
      organization and cell wall metabolism, which can be related to growth of berries
      and firmness loss characteristic to this stage of development. This high
      metabolic activity could be associated with an increase in the transcription of
      genes related with glycolysis and respiration, unexpected for a non-climacteric
      fruit ripening.

PMID- 29320528
TI  - Developmental finite element analysis of cichlid pharyngeal jaws: Quantifying the
      generation of a key innovation.
AB  - Advances in imaging and modeling facilitate the calculation of biomechanical
      forces in biological specimens. These factors play a significant role during
      ontogenetic development of cichlid pharyngeal jaws, a key innovation responsible
      for one of the most prolific species diversifications in recent times. MicroCT
      imaging of radiopaque-stained vertebrate embryos were used to accurately capture
      the spatial relationships of the pharyngeal jaw apparatus in two cichlid species
      (Haplochromis elegans and Amatitlania nigrofasciata) for the purpose of creating
      a time series of developmental stages using finite element models, which can be
      used to assess the effects of biomechanical forces present in a system at
      multiple points of its ontogeny. Changes in muscle vector orientations, bite
      forces, force on the neurocranium where cartilage originates, and stress on upper
      pharyngeal jaws are analyzed in a comparative context. In addition, microCT
      scanning revealed the presence of previously unreported cement glands in A.
      nigrofasciata. The data obtained provide an underrepresented dimension of
      information on physical forces present in developmental processes and assist in
      interpreting the role of developmental dynamics in evolution.

PMID- 29320529
TI  - How exogenous nitric oxide regulates nitrogen assimilation in wheat seedlings
      under different nitrogen sources and levels.
AB  - Nitrogen (N) is one of the most important nutrients for plants and nitric oxide
      (NO) as a signaling plant growth regulator involved in nitrogen assimilation.
      Understanding the influence of exogenous NO on nitrogen metabolism at the gene
      expression and enzyme activity levels under different sources of nitrogen is
      vitally important for increasing nitrogen use efficiency (NUE). This study
      investigated the expression of key genes and enzymes in relation to nitrogen
      assimilation in two Australian wheat cultivars, a popular high NUE cv. Spitfire
      and a normal NUE cv. Westonia, under different combinations of nitrogen and
      sodium nitroprusside (SNP) as the NO donor. Application of NO increased the gene
      expressions and activities of nitrogen assimilation pathway enzymes in both
      cultivars at low levels of nitrogen. At high nitrogen supplies, the expressions
      and activities of N assimilation genes increased in response to exogenous NO only
      in cv. Spitfire but not in cv. Westonia. Exogenous NO caused an increase in leaf
      NO content at low N supplies in both cultivars, while under high nitrogen
      treatments, cv. Spitfire showed an increase under ammonium nitrate (NH4NO3)
      treatment but cv. Westonia was not affected. N assimilation gene expression and
      enzyme activity showed a clear relationship between exogenous NO, N concentration
      and N forms in primary plant nitrogen assimilation. Results reveal the possible
      role of NO and different nitrogen sources on nitrogen assimilation in Triticum
      aestivum plants.

PMID- 29320530
TI  - The amyloid precursor protein derivative, APP96-110, is efficacious following
      intravenous administration after traumatic brain injury.
AB  - Following traumatic brain injury (TBI) neurological damage is ongoing through a
      complex cascade of primary and secondary injury events in the ensuing minutes,
      days and weeks. The delayed nature of secondary injury provides a valuable window
      of opportunity to limit the consequences with a timely treatment. Recently, the
      amyloid precursor protein (APP) and its derivative APP96-110 have shown
      encouraging neuroprotective activity following TBI following an
      intracerebroventricular administration. Nevertheless, its broader clinical
      utility would be enhanced by an intravenous (IV) administration. This study
      assessed the efficacy of IV APP96-110, where a dose-response for a single dose of
      0.005mg/kg- 0.5mg/kg APP96-110 at either 30 minutes or 5 hours following moderate
      severe diffuse impact-acceleration injury was performed. Male Sprague-Dawley rats
      were assessed daily for 3 or 7 days on the rotarod to examine motor outcome, with
      a separate cohort of animals utilised for immunohistochemistry analysis 3 days
      post-TBI to assess axonal injury and neuroinflammation. Animals treated with
      0.05mg/kg or 0.5mg/kg APP96-110 after 30 minutes demonstrated significant
      improvements in motor outcome. This was accompanied by a reduction in axonal
      injury and neuroinflammation in the corpus callosum at 3 days post-TBI, whereas
      0.005mg/kg had no effect. In contrast, treatment with 0.005m/kg or 0.5mg/kg APP96
      110 at 5 hours post-TBI demonstrated significant improvements in motor outcome
      over 3 days, which was accompanied by a reduction in axonal injury in the corpus
      callosum. This demonstrates that APP96-110 remains efficacious for up to 5 hours
      post-TBI when administered IV, and supports its development as a novel
      therapeutic compound following TBI.

PMID- 29320531
TI  - Integrating community pharmacy into community based anti-retroviral therapy
      program: A pilot implementation in Abuja, Nigeria.
AB  - BACKGROUND: The landscape of Human Immunodeficiency Virus (HIV) epidemic control
      is shifting with the United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90
      benchmarks for epidemic control. Community-based Antiretroviral Therapy (CART)
      models have improved treatment uptake and demonstrated good clinical outcomes. We
      assessed the feasibility of integrating community pharmacy as a task shift
      structure for differentiated community ART in Abuja-Nigeria. METHODS: Stable
      patients on first line ART regimens from public health facilities were referred
      to community pharmacies in different locations within the Federal Capital
      Territory, Abuja for prescription refills and treatment maintenance. Bio
      demographic and clinical data were collected from February 25, 2016 to May 31st,
      2017 and descriptive statistics analysis applied. The outcomes of measure were
      prescription refill and patient retention in care at the community pharmacy.
      RESULTS: Almost 10% of stable patients on treatment were successfully devolved
      from eight health facilities to ten community pharmacies. Median age of the
      participants was 35 years [interquartile range (IQR); 30, 41] with married women
      in the majority. Prescription refill was 100% and almost all the participants
      (99.3%) were retained in care after they were devolved to the community
      pharmacies. Only one participant was lost-to-follow-up as a result of death.
      CONCLUSION: Excellent prescription refill and high retention in care with very
      low loss-to-follow-up were associated with the community pharmacy model. The use
      of community pharmacy for community ART is feasible in Nigeria. We recommend the
      scale up of the model in all the 36 states of Nigeria.

PMID- 29320532
TI  - Automatic outer and inner breast tissue segmentation using multi-parametric MRI
      images of breast tumor patients.
AB  - The objectives of the study were to develop a framework for automatic outer and
      inner breast tissue segmentation using multi-parametric MRI images of the breast
      tumor patients; and to perform breast density and tumor tissue analysis. MRI of
      the breast was performed on 30 patients at 3T-MRI. T1, T2 and PD-weighted(W)
      images, with and without fat saturation(WWFS), and dynamic-contrast-enhanced(DCE)
      MRI data were acquired. The proposed automatic segmentation approach was
      performed in two steps. In step-1, outer segmentation of breast tissue from rest
      of body parts was performed on structural images (T2-W/T1-W/PD-W without fat
      saturation images) using automatic landmarks detection technique based on
      operations like profile screening, Otsu thresholding, morphological operations
      and empirical observation. In step-2, inner segmentation of breast tissue into
      fibro-glandular(FG), fatty and tumor tissue was performed. For validation of
      breast tissue segmentation, manual segmentation was carried out by two
      radiologists and similarity coefficients(Dice and Jaccard) were computed for
      outer as well as inner tissues. FG density and tumor volume were also computed
      and analyzed. The proposed outer and inner segmentation approach worked well for
      all the subjects and was validated by two radiologists. The average Dice and
      Jaccard coefficients value for outer segmentation using T2-W images, obtained by
      two radiologists, were 0.977 and 0.951 respectively. These coefficient values for
      FG tissue were 0.915 and 0.875 respectively whereas for tumor tissue, values were
      0.968 and 0.95 respectively. The volume of segmented tumor ranged over 2.1 cm3
      7.08 cm3. The proposed approach provided automatic outer and inner breast tissue
      segmentation, which enables automatic calculations of breast tissue density and
      tumor volume. This is a complete framework for outer and inner breast
      segmentation method for all structural images.

PMID- 29320533
TI  - What makes a rhythm complex? The influence of musical training and accent type on
      beat perception.
AB  - Perception of a regular beat in music is inferred from different types of
      accents. For example, increases in loudness cause intensity accents, and the
      grouping of time intervals in a rhythm creates temporal accents. Accents are
      expected to occur on the beat: when accents are "missing" on the beat, the beat
      is more difficult to find. However, it is unclear whether accents occurring off
      the beat alter beat perception similarly to missing accents on the beat.
      Moreover, no one has examined whether intensity accents influence beat perception
      more or less strongly than temporal accents, nor how musical expertise affects
      sensitivity to each type of accent. In two experiments, we obtained ratings of
      difficulty in finding the beat in rhythms with either temporal or intensity
      accents, and which varied in the number of accents on the beat as well as the
      number of accents off the beat. In both experiments, the occurrence of accents on
      the beat facilitated beat detection more in musical experts than in musical
      novices. In addition, the number of accents on the beat affected beat finding
      more in rhythms with temporal accents than in rhythms with intensity accents. The
      effect of accents off the beat was much weaker than the effect of accents on the
      beat and appeared to depend on musical expertise, as well as on the number of
      accents on the beat: when many accents on the beat are missing, beat perception
      is quite difficult, and adding accents off the beat may not reduce beat
      perception further. Overall, the different types of accents were processed
      qualitatively differently, depending on musical expertise. Therefore, these
      findings indicate the importance of designing ecologically valid stimuli when
      testing beat perception in musical novices, who may need different types of
      accent information than musical experts to be able to find a beat. Furthermore,
      our findings stress the importance of carefully designing rhythms for social and
      clinical applications of beat perception, as not all listeners treat all rhythms
      alike.

PMID- 29320534
TI  - The endothelial specific isoform of type XVIII collagen correlates to annual
      bleeding rate in haemophilia patients.
AB  - INTRODUCTION: The medical need in the haemophilic (HF) field to reduce bleeding
      incidents requires measurement of the annual bleeding rate (ABR) in
      haemophiliacs. Vascular rupture is associated with damage to the vascular
      endothelium causing exposure of the basement membrane. Endothelial cells and
      matrix impairment may be associated with joint bleeds and later development of HF
      arthropathy. Imbalanced extracellular matrix turnover is a central pathological
      feature in many diseases consequent to epithelial or endothelial cell damage.
      Type XVIII collagen is an essential basement membrane component, with an
      endothelial specific isoform. AIM: To quantify the basement membrane specifically
      for the endothelial cells, as that may have particular relevance to endothelial
      cell stability and rupture in haemophiliacs. A newly developed ELISA assay
      detecting endothelial type XVIII collagen (COL-18N) was used to assess the
      clinical relevance of endothelial basement membrane turnover in patients
      diagnosed with HF arthropathy and correlation to ABR. METHODS: We developed an
      ELISA assay for quantification of COL-18N. Serum from 35 male HF patients was
      investigated using the COL-18N ELISA. RESULTS: COL-18N correlated to the ABR of
      haemophiliacs, r = 0.45, P<0.006. CONCLUSION: Vascular rupture and consequent
      bleeding are associated with joint damage and deterioration of life quality in
      haemophiliacs. Quantification of ABR is an important part in efficacy assessment
      of different interventions, and the benchmark of these. Objective biomarkers
      reflecting endothelial dysfunction, vascular leaks and rupture, like the COL-18N
      biomarker that associate with ABR, may assist in identifying the most optimal
      treatment and monitoring of HF patients.

PMID- 29320535
TI  - Rhombic organization of microvilli domains found in a cell model of the human
      intestine.
AB  - Symmetry is rarely found on cellular surfaces. An exception is the brush border
      of microvilli, which are essential for the proper function of transport
      epithelia. In a healthy intestine, they appear densely packed as a 2D-hexagonal
      lattice. For in vitro testing of intestinal transport the cell line Caco-2 has
      been established. As reported by electron microscopy, their microvilli arrange
      primarily in clusters developing secondly into a 2D-hexagonal lattice. Here,
      atomic force microscopy (AFM) was employed under aqueous buffer conditions on
      Caco-2 cells, which were cultivated on permeable filter membranes for optimum
      differentiation. For analysis, the exact position of each microvillus was
      detected by computer vision; subsequent Fourier transformation yielded the type
      of 2D-lattice. It was confirmed, that Caco-2 cells can build a hexagonal lattice
      of microvilli and form clusters. Moreover, a second type of arrangement was
      discovered, namely a rhombic lattice, which appeared at sub-maximal densities of
      microvilli with (29 +/- 4) microvilli / MUm2. Altogether, the findings indicate
      the existence of a yet undescribed pattern in cellular organization.

PMID- 29320536
TI  - Socio-economic and demographic determinants affecting participation in the
      Swedish cervical screening program: A population-based case-control study.
AB  - BACKGROUND: Cervical screening programs are highly protective for cervical
      cancer, but only for women attending screening procedure. OBJECTIVE: Identify
      socio-economic and demographic determinants for non-attendance in cervical
      screening. METHODS: Design: Population-based case-control study. Setting: Sweden.
      Population: Source population was all women eligible for screening. Based on
      complete screening records, two groups of women aged 30-60 were compared. The
      case group, non-attending women, (N = 314,302) had no smear registered for 6-8
      years. The control group (N = 266,706) attended within 90 days of invitation.
      Main outcome measures: Risk of non-attendance by 9 groups of socioeconomic and
      demographic variables. Analysis: Unadjusted odds ratios (OR) and OR after
      adjustment for all variables in logistic regression models were calculated.
      RESULTS: Women with low disposable family income (adjOR 2.06; 95% confidence
      interval (CI) 2.01-2.11), with low education (adjOR 1.77; CI 1.73-1.81) and not
      cohabiting (adjOR 1.47; CI 1.45-1.50) were more likely to not attend cervical
      screening. Other important factors for non-attendance were being outside the
      labour force and receiving welfare benefits. Swedish counties are responsible for
      running screening programs; adjusted OR for non-participation in counties ranged
      from OR 4.21 (CI 4.06-4.35) to OR 0.54 (CI 0.52-0.57), compared to the reference
      county. Being born outside Sweden was a risk factor for non-attendance in the
      unadjusted analysis but this disappeared in certain large groups after adjustment
      for socioeconomic factors. CONCLUSION: County of residence and socio-economic
      factors were strongly associated with lower attendance in cervical screening,
      while being born in another country was of less importance. This indicates
      considerable potential for improvement of cervical screening attendance in
      several areas if best practice of routines is adopted.

PMID- 29320537
TI  - Correlation of a new index reflecting the fluctuation of parasympathetic tone and
      fetal acidosis in an experimental study in a sheep model.
AB  - The autonomic nervous system plays a leading role in the control of fetal
      homeostasis. Fetal heart rate variability (HRV) analysis is a reflection of its
      activity. We developed a new index (the Fetal Stress Index, FSI) reflecting
      parasympathetic tone. The objective of this study was to evaluate this index as a
      predictor of fetal acid-base status. This was an experimental study on
      chronically instrumented fetal lambs (n = 11, surgery at 128 +/- 2 days
      gestational age, term = 145 days). The model was based on 75% occlusion of the
      umbilical cord for a maximum of 120 minutes or until an arterial pH <= 7.20 was
      reached. Hemodynamic, gasometric and FSI parameters were recorded throughout the
      experimentation. We studied the FSI during the 10 minutes prior to pH samplings
      and compared values for pH>7.20 and pH<= 7.20. In order to analyze the FSI
      evolution during the 10 minutes periods, we analyzed the minimum, maximum and
      mean values of the FSI (respectively FSImin, FSImax and FSImean) over the
      periods. 11 experimentations were performed. During occlusion, the heart rate
      dropped with an increase in blood pressure (respectively 160(155-182) vs 106(101
      120) bpm and 42(41-45) vs 58(55-62) mmHg after occlusion). The FSImin was 38.6
      (35.2-43.3) in the group pH>7.20 and was higher in the group pH less than 7.20
      (46.5 (43.3-52.0), p = 0.012). The correlation of FSImin was significant for
      arterial pH (coefficient of -0.671; p = 0.004) and for base excess (coefficient
      of -0.632; p = 0.009). The correlations were not significant for the other
      parameters. In conclusion, our new index seems well correlated with the fetal
      acid-base status. Other studies must be carried out in a situation close to the
      physiology of labor by sequential occlusion of the cord.

PMID- 29320538
TI  - Germline and somatic variant identification using BGISEQ-500 and HiSeq X Ten
      whole genome sequencing.
AB  - Technological innovation and increased affordability have contributed to the
      widespread adoption of genome sequencing technologies in biomedical research. In
      particular large cancer research consortia have embraced next generation
      sequencing, and have used the technology to define the somatic mutation landscape
      of multiple cancer types. These studies have primarily utilised the Illumina
      HiSeq platforms. In this study we performed whole genome sequencing of three
      malignant pleural mesothelioma and matched normal samples using a new platform,
      the BGISEQ-500, and compared the results obtained with Illumina HiSeq X Ten.
      Germline and somatic, single nucleotide variants and small insertions or
      deletions were independently identified from data aligned human genome reference.
      The BGISEQ-500 and HiSeq X Ten platforms showed high concordance for germline
      calls with genotypes from SNP arrays (>99%). The germline and somatic single
      nucleotide variants identified in both sequencing platforms were highly
      concordant (86% and 72% respectively). These results indicate the potential
      applicability of the BGISEQ-500 platform for the identification of somatic and
      germline single nucleotide variants by whole genome sequencing. The BGISEQ-500
      datasets described here represent the first publicly-available cancer genome
      sequencing performed using this platform.

PMID- 29320539
TI  - The impact of electronic consultation on a Canadian tertiary care pediatric
      specialty referral system: A prospective single-center observational study.
AB  - BACKGROUND: Champlain BASETM (Building Access to Specialists through
      eConsultation) is a web-based asynchronous electronic communication service that
      allows primary-care- practitioners (PCPs) to submit "elective" clinical questions
      to a specialist. For adults, PCPs have reported improved access and timeliness to
      specialist advice, averted face-to-face specialist referrals in up to 40% of
      cases and high provider satisfaction. OBJECTIVE: To determine whether the
      expansion of eConsult to a pediatric setting would result in similar measures of
      improved healthcare system process and high provider acceptance reported in
      adults. DESIGN: Prospective observational cohort study. SETTING: Single Canadian
      tertiary-care academic pediatric hospital (June 2014-16) servicing 1.2 million
      people. PARTICIPANTS: 1. PCPs already using eConsult. 2.Volunteer pediatric
      specialists provided services in addition to their regular workload. 3.Pediatric
      patients (< 18 years-old) referred for none-acute care conditions. MAIN OUTCOMES
      AND MEASURES: Specialty service utilization and access, impact on PCP course-of
      action and referral-patterns and survey-based provider satisfaction data were
      collected. RESULTS: 1064 eConsult requests from 367 PCPs were answered by 23
      pediatric specialists representing 14 specialty-services. The top three
      specialties represented were: General Pediatrics 393 cases (36.9%), Orthopedics
      162 (15.2%) and Psychiatry 123 (11.6%). Median specialist response time was 0.9
      days (range <1 hour-27 days), most consults (63.2%) required <10minutes to
      complete and 21/21(100%) specialist survey-respondents reported minimal workload
      burden. For 515/1064(48.4%) referrals, PCPs received advice for a new or
      additional course of action; 391/1064(36.7%) referrals resulted in an averted
      face-to-face specialist visit. In 9 specialties with complete data, the median
      wait-time was significantly less (p<0.001) for an eConsult (1 day, 95%CI:0.9-1.2)
      compared with a face-to-face referral (132 days; 95%CI:127-136). The majority
      (>93.3%) of PCPs rated eConsult as very good/excellent value for both patients
      and themselves. All specialist survey-respondents indicated eConsult should be a
      continued service. CONCLUSIONS AND RELEVANCE: Similar to adults, eConsult
      improves PCP access and timeliness to elective pediatric specialist advice and
      influences their care decisions, while reporting high end-user satisfaction.
      Further study is warranted to assess impact on resource utilization and clinical
      outcomes.

PMID- 29320540
TI  - Discerning suicide in drug intoxication deaths: Paucity and primacy of suicide
      notes and psychiatric history.
AB  - OBJECTIVE: A paucity of corroborative psychological and psychiatric evidence may
      be inhibiting detection of drug intoxication suicides in the United States. We
      evaluated the relative importance of suicide notes and psychiatric history in the
      classification of suicide by drug intoxication versus firearm (gunshot wound)
      plus hanging/suffocation-the other two major, but overtly violent methods.
      METHODS: This observational multilevel (individual/county), multivariable study
      employed a generalized linear mixed model (GLMM) to analyze pooled suicides and
      undetermined intent deaths, as possible suicides, among the population aged 15
      years and older in the 17 states participating in the National Violent Death
      Reporting System throughout 2011-2013. The outcome measure was relative odds of
      suicide versus undetermined classification, adjusted for demographics,
      precipitating circumstances, and investigation characteristics. RESULTS: A
      suicide note, prior suicide attempt, or affective disorder was documented in less
      than one-third of suicides and one-quarter of undetermined deaths. The prevalence
      gaps were larger among drug intoxication cases than gunshot/hanging cases. The
      latter were more likely than intoxication cases to be classified as suicide
      versus undetermined manner of death (adjusted odds ratio [OR], 41.14; 95% CI,
      34.43-49.15), as were cases documenting a suicide note (OR, 33.90; 95% CI, 26.11
      44.05), prior suicide attempt (OR, 2.42; 95% CI, 2.11-2.77), or depression (OR,
      1.61; 95% CI, 1.38 to 1.88), or bipolar disorder (OR, 1.41; 95% CI, 1.10-1.81).
      Stratification by mechanism/cause intensified the association between a note and
      suicide classification for intoxication cases (OR, 45.43; 95% CI, 31.06-66.58).
      Prior suicide attempt (OR, 2.64; 95% CI, 2.19-3.18) and depression (OR, 1.48; 95%
      CI, 1.17-1.87) were associated with suicide classification in intoxication but
      not gunshot/hanging cases. CONCLUSIONS: Without psychological/psychiatric
      evidence contributing to manner of death classification, suicide by drug
      intoxication in the US is likely profoundly under-reported. Findings harbor
      adverse implications for surveillance, etiologic understanding, and prevention of
      suicides and drug deaths.

PMID- 29320541
TI  - Agent-based modeling of the interaction between CD8+ T cells and Beta cells in
      type 1 diabetes.
AB  - We propose an agent-based model for the simulation of the autoimmune response in
      T1D. The model incorporates cell behavior from various rules derived from the
      current literature and is implemented on a high-performance computing system,
      which enables the simulation of a significant portion of the islets in the mouse
      pancreas. Simulation results indicate that the model is able to capture the
      trends that emerge during the progression of the autoimmunity. The multi-scale
      nature of the model enables definition of rules or equations that govern cellular
      or sub-cellular level phenomena and observation of the outcomes at the tissue
      scale. It is expected that such a model would facilitate in vivo clinical studies
      through rapid testing of hypotheses and planning of future experiments by
      providing insight into disease progression at different scales, some of which may
      not be obtained easily in clinical studies. Furthermore, the modular structure of
      the model simplifies tasks such as the addition of new cell types, and the
      definition or modification of different behaviors of the environment and the
      cells with ease.

PMID- 29320542
TI  - Ancient mitogenomes of Phoenicians from Sardinia and Lebanon: A story of
      settlement, integration, and female mobility.
AB  - The Phoenicians emerged in the Northern Levant around 1800 BCE and by the 9th
      century BCE had spread their culture across the Mediterranean Basin, establishing
      trading posts, and settlements in various European Mediterranean and North
      African locations. Despite their widespread influence, what is known of the
      Phoenicians comes from what was written about them by the Greeks and Egyptians.
      In this study, we investigate the extent of Phoenician integration with the
      Sardinian communities they settled. We present 14 new ancient mitogenome
      sequences from pre-Phoenician (~1800 BCE) and Phoenician (~700-400 BCE) samples
      from Lebanon (n = 4) and Sardinia (n = 10) and compare these with 87 new complete
      mitogenomes from modern Lebanese and 21 recently published pre-Phoenician ancient
      mitogenomes from Sardinia to investigate the population dynamics of the
      Phoenician (Punic) site of Monte Sirai, in southern Sardinia. Our results
      indicate evidence of continuity of some lineages from pre-Phoenician populations
      suggesting integration of indigenous Sardinians in the Monte Sirai Phoenician
      community. We also find evidence of the arrival of new, unique mitochondrial
      lineages, indicating the movement of women from sites in the Near East or North
      Africa to Sardinia, but also possibly from non-Mediterranean populations and the
      likely movement of women from Europe to Phoenician sites in Lebanon. Combined,
      this evidence suggests female mobility and genetic diversity in Phoenician
      communities, reflecting the inclusive and multicultural nature of Phoenician
      society.

PMID- 29320543
TI  - Distinct expression of functionally glycosylated alpha-dystroglycan in muscle and
      non-muscle tissues of FKRP mutant mice.
AB  - The glycosylation of alpha-dystroglycan (alpha-DG) is crucial in maintaining
      muscle cell membrane integrity. Dystroglycanopathies are identified by the loss
      of this glycosylation leading to a breakdown of muscle cell membrane integrity
      and eventual degeneration. However, a small portion of fibers expressing
      functionally glycosylated alpha-DG (F-alpha-DG) (revertant fibers, RF) have been
      identified. These fibers are generally small in size, centrally nucleated and
      linked to regenerating fibers. Examination of different muscles have shown
      various levels of RFs but it is unclear the extent of which they are present.
      Here we do a body-wide examination of muscles from the FKRP-P448L mutant mouse
      for the prevalence of RFs. We have identified great variation in the distribution
      of RF in different muscles and tissues. Triceps shows a large increase in RFs and
      together with centrally nucleated fibers whereas the pectoralis shows a reduction
      in revertant but increase in centrally nucleated fibers from 6 weeks to 6 months
      of age. We have also identified that the sciatic nerve with near normal levels of
      F-alpha-DG in the P448Lneo- mouse with reduced levels in the P448Lneo+ and absent
      in LARGEmyd. The salivary gland of LARGEmyd mice expresses high levels of F-alpha
      DG. Interestingly the same glands in the P448Lneo-and to a lesser degree in
      P448Lneo+ also maintain considerable amount of F-alpha-DG, indicating the non
      proliferating epithelial cells have a molecular setting permitting glycosylation.

PMID- 29320544
TI  - Diversity patterns, Leishmania DNA detection, and bloodmeal identification of
      Phlebotominae sand flies in villages in northern Colombia.
AB  - Leishmaniases are neglected tropical diseases exhibiting complex transmission
      cycles due to the number of parasite species circulating, sand fly species acting
      as vectors and infected mammals, including humans, which are defined in the New
      World as accidental hosts. However, current transmission scenarios are changing,
      and the disease is no longer exclusively related to forested areas but urban
      transmission foci occur, involving some species of domestic animals as suspected
      reservoirs. The aim of this study was to determine the transmission cycles in
      urban environments by evaluating sand fly diversity, detection of Leishmania DNA,
      and bloodmeal sources through intra and peridomestic collections. The study was
      carried out in Colombia, in 13 municipalities of Cordoba department, implementing
      a methodology that could be further used for the evaluation of vector-borne
      diseases in villages or towns. Our sampling design included 24 houses randomly
      selected in each of 15 villages distributed in 13 municipalities, which were
      sampled in two seasons in 2015 and 2016. Sand flies were collected using CDC
      light traps placed in intra and peridomestic habitats. In addition to the
      morphological identification, molecular identification through DNA barcodes was
      also performed. A total of 19,743 sand flies were collected and 13,848 of them
      (10,268 females and 3,580 males) were used in molecular procedures. Circulation
      of two known parasite species-Leishmania infantum and Leishmania panamensis was
      confirmed. Blood source analyses showed that sand flies fed on humans,
      particularly in the case of the known L. infantum vector, P. evansi; further
      analyses are advised to evaluate the reservoirs involved in parasite
      transmission. Our sampling design allowed us to evaluate potential transmission
      cycles on a department scale, by defining suspected vector species, parasite
      species present in different municipalities and feeding habits.

PMID- 29320545
TI  - Adaptation and validation of the Spanish version of the ORTO-15 questionnaire for
      the diagnosis of orthorexia nervosa.
AB  - The aim of this study was the validation and analysis of the psychometric
      properties of a Spanish translation of the ORTO-15 questionnaire; an instrument
      designed to assess orthorexia nervosa behavior. Four hundred and fifty-four
      Spanish university students (65% women) aged between 18 and 51 years (M = 21.48
      +/- 0.31) completed the Spanish version of ORTO-15 and the Eating Disorders
      Inventory-2 (EDI-2). The Principal Component Analysis suggested a three-factor
      structure for the abbreviated 11-item version of the instrument. The internal
      consistency of the measurement was adequate (Cronbach's alpha = 0.80). The
      proposed test demonstrated a good predictive capacity at a threshold value of <25
      (efficiency 84%, sensitivity 75% and specificity 84%). Our results support the
      psychometric properties of the proposed Spanish shortened-version of the ORTO-15
      as being a reliable tool for assessing orthorexia nervosa. Its use is expected to
      greatly contribute to a better understanding of the impact of this disorder in
      Spain.

PMID- 29320546
TI  - RPA and XPA interaction with DNA structures mimicking intermediates of the late
      stages in nucleotide excision repair.
AB  - Replication protein A (RPA) and the xeroderma pigmentosum group A (XPA) protein
      are indispensable for both pathways of nucleotide excision repair (NER). Here we
      analyze the interaction of RPA and XPA with DNA containing a flap and different
      size gaps that imitate intermediates of the late NER stages. Using gel mobility
      shift assays, we found that RPA affinity for DNA decreased when DNA contained
      both extended gap and similar sized flap in comparison with gapped-DNA structure.
      Moreover, crosslinking experiments with the flap-gap DNA revealed that RPA
      interacts mainly with the ssDNA platform within the long gap and contacts flap in
      DNA with a short gap. XPA exhibits higher affinity for bubble-DNA structures than
      to flap-gap-containing DNA. Protein titration analysis showed that formation of
      the RPA-XPA-DNA ternary complex depends on the protein concentration ratio and
      these proteins can function as independent players or in tandem. Using
      fluorescently-labelled RPA, direct interaction of this protein with XPA was
      detected and characterized quantitatively. The data obtained allow us to suggest
      that XPA can be involved in the post-incision NER stages via its interaction with
      RPA.

PMID- 29320548
TI  - Primed for death: Law enforcement-citizen homicides, social media, and
      retaliatory violence.
AB  - We examine whether retaliatory violence exists between law enforcement and
      citizens while controlling for any social media contagion effect related to prior
      fatal encounters. Analyzed using a trivariate dynamic structural vector
      autoregressive model, daily time-series data over a 21-month period captured the
      frequencies of police killed in the line of duty, police deadly use of force
      incidents, and social media coverage. The results support a significant
      retaliatory violence effect against minorities by police, yet there is no
      evidence of retaliatory violence against law enforcement officers by minorities.
      Also, social media coverage of the Black Lives Matter movement increases the risk
      of fatal victimization to both law enforcement officers and minorities. Possible
      explanations for these results are based in rational choice and terror management
      theories.

PMID- 29320547
TI  - Dyslipidemia, chronic inflammation, and subclinical atherosclerosis in children
      and adolescents infected with HIV: The PositHIVe Health Study.
AB  - HIV-infected children and adolescents may be at risk for cardiovascular disease
      due to chronic inflammation and exacerbation of risk factors. The aim of this
      study was as follows: 1) compare cardiovascular risk factors, chronic
      inflammation, and carotid intima-media thickness (IMTc) between the HIV and
      control groups; 2) determine the association of HIV and antiretroviral (ART)
      regimens with cardiovascular risk factors, chronic inflammation, and IMTc; and 3)
      identify variables associated with elevated IMTc. Cross-sectional analysis of 130
      children and adolescents, 8-15 years of age, divided into HIV-infected (n = 65)
      and healthy control (n = 65) participants. Body fat, blood pressure, glycemia,
      insulin, and glycated hemoglobin, total cholesterol and fractions (LDL-C and HDL
      C), triglycerides, C-reactive protein (CRP), interleukin (IL)-6, tumor necrosis
      factor-alpha (TNF-alpha), and the IMTc were measured. The results showed HIV
      infected children and adolescents had higher levels of glycemia (87.9 vs. 75.9
      mg.dL-1, p< 0.001), LDL-c (94.7 vs. 79.5 mg.dL-1, p = 0.010), triglycerides
      (101.2 vs. 61.6 mg.dL-1, p< 0.001), CRP (1.6 vs. 1.0 mg.L-1, p = 0.007), IL-6
      (1.42 vs. 0.01 pg.mL-1, p< 0.001), TNF-alpha (0.49 vs. 0.01 pg.mL-1, p< 0.001),
      mean IMTc (0.526 vs. 0.499 mm, p = 0.009), and lower HDL-c (53.7 vs. 69.4 mg.dL
      1, p< 0.001) compared to controls. Systolic blood pressure (beta = 0.006, p =
      0.004) and TNF-alpha (beta = -0.033, p = 0.029) accounted for 16% of IMTc
      variability in HIV-infected children and adolescents. In patients using protease
      inhibitors-based ART, male gender (beta = -0.186, p = 0.008), trunk body fat
      (beta = -0.011, p = 0.006), glucose (beta = 0.005, p = 0.046), and IL-6 (beta =
      0.017, p = 0.039) accounted for 28% of IMTc variability. HIV-infected children
      and adolescents may be at risk for premature atherosclerosis due to chronic
      inflammation and dyslipidemia. Interventions with the potential to improve lipid
      profile, mitigate inflammation, and reduce cardiovascular risk are needed.

PMID- 29320550
TI  - Longitudinal micro-CT as an outcome measure of interstitial lung disease in TNF
      transgenic mice.
AB  - INTRODUCTION: Rheumatoid arthritis associated interstitial lung disease (RA-ILD)
      is a debilitating condition with poor survival prognosis. High resolution
      computed tomography (CT) is a common clinical tool to diagnose RA-ILD, and is
      increasingly being adopted in pre-clinical studies. However, murine models
      recapitulating RA-ILD are lacking, and CT outcomes for inflammatory lung disease
      have yet to be formally validated. To address this, we validate MUCT outcomes for
      ILD in the tumor necrosis factor transgenic (TNF-Tg) mouse model of RA. METHODS:
      Cross sectional MUCT was performed on cohorts of male TNF-Tg mice and their WT
      littermates at 3, 4, 5.5 and 12 months of age (n = 4-6). Lung MUCT outcomes
      measures were determined by segmentation of the MUCT datasets to generate Aerated
      and Tissue volumes. After each scan, lungs were obtained for histopathology and 3
      sections stained with hematoxylin and eosin. Automated histomorphometry was
      performed to quantify the tissue area (nuclei, cytoplasm, and extracellular
      matrix) and aerated area (white space) within the tissue sections. Spearman's
      correlation coefficients were used to evaluate the extent of association between
      MUCT imaging and histopathology endpoints. RESULTS: TNF-Tg mice had significantly
      greater tissue volume, total lung volume and mean intensity at all timepoints
      compared to age matched WT littermates. Histomorphometry also demonstrated a
      significant increase in tissue area at 3, 4, and 5.5 months of age in TNF-Tg
      mice. Lung tissue volume was correlated with lung tissue area (rho = 0.81,
      p<0.0001), and normalize lung aerated volume was correlated with normalized lung
      air area (rho = 0.73, p<0.0001). CONCLUSIONS: We have validated in vivo MUCT as a
      quantitative biomarker of ILD in mice. Further, development of longitudinal
      measures is critical for dissecting pathologic progression of ILD, and MUCT is a
      useful non-invasive method to study lung inflammation in the TNF-Tg mouse model.

PMID- 29320549
TI  - Assessing adverse effects of intra-articular botulinum toxin A in healthy Beagle
      dogs: A placebo-controlled, blinded, randomized trial.
AB  - OBJECTIVE: To investigate the clinical, cytological, and histopathological
      adverse effects of intra-articularly injected botulinum toxin A in dogs and to
      study whether the toxin spreads from the joint after the injection. METHODS: A
      longitudinal, placebo-controlled, randomized clinical trial was conducted with
      six healthy laboratory Beagle dogs. Stifle joints were randomized to receive
      either 30 IU of onabotulinum toxin A or placebo in a 1:1 ratio. Adverse effects
      and spread of the toxin were examined by evaluating dynamic and static weight
      bearing of the injected limbs, by assessing painless range of motion and pain on
      palpation of joints, and by performing synovial fluid analysis, neurological
      examination, and electrophysiological recordings at different examination time
      points in a 12-week period after the injections. The dogs were then euthanized
      and autopsy and histopathological examination of joint structures and adjacent
      muscles and nerves were performed. RESULTS: Intra-articular botulinum toxin A did
      not cause local weakness or injection site pain. Instead, static weight-bearing
      and painless range of motion of stifle joints decreased in the placebo limbs. No
      clinically significant abnormalities associated with intra-articular botulinum
      toxin A were detected in the neurological examinations. Electrophysiological
      recordings showed low compound muscle action potentials in two dogs in the
      botulinum toxin A-injected limb. No significant changes were detected in the
      synovial fluid. Autopsy and histopathological examination of the joint and
      adjacent muscles and nerves did not reveal histopathological adverse effects of
      the toxin. CONCLUSION: Intra-articular botulinum toxin A does not produce
      significant clinical, cytological, or histopathological adverse effects in
      healthy dogs. Based on the electrophysiological recordings, the toxin may spread
      from the joint, but its clinical impact seems to be low.

PMID- 29320551
TI  - Are oral deformities in tadpoles accurate indicators of anuran chytridiomycosis?
AB  - We evaluated the use of oral deformities as reliable proxies for determining
      Batrachochytrium dendrobatidis (Bd) infection in tadpoles of six anuran species
      of the Atlantic Forest in southeastern Brazil. We examined oral discs of 2156
      tadpoles of six species of anurans collected in 2016: Aplastodiscus albosignatus,
      Boana albopunctata, Boana faber, Scinax hayii, Crossodactylus caramaschii, and
      Physalaemus cuvieri. Three oral deformities were recognized: lack of
      keratinization only in upper and/or lower jaw sheaths, lack of keratinization
      only in upper or lower tooth rows, and both deformities together. A subsample
      composed of all the individuals possessing oral deformities (N = 195) plus
      randomly selected individuals without oral deformities (N = 184) were tested for
      Bd via qPCR. Oral deformities were observed in all six species, but only five
      were infected with Bd. Since we found that dekeratinization of tooth rows was not
      associated with the presence of Bd in any of the studied species we used a new
      proxy (jaw sheaths dekeratinization with or without dekeratinization in tooth
      rows: JSD-proxy) for Bd detection. Our results showed a nonrandom relationship
      between Bd infection and JSD-proxy in three species of the family Hylidae.
      However, the use of JSD-proxy for Bd detection in these species resulted in up to
      30.8% false positives and up to 29.3% false negatives. The use of the JSD-proxy
      in species for which no relationship was found reached 100% of false positives.
      We conclude that the use of oral dekeratinization as a generalized proxy for Bd
      detection in tadpoles should not be used as a single diagnosis technique.

PMID- 29320552
TI  - First report of occult hepatitis B infection among ART naive HIV seropositive
      individuals in Maputo, Mozambique.
AB  - BACKGROUND: The prevalence of hepatitis B virus (HBV) infection and human
      immunodeficiency virus (HIV) infection in Mozambique is one of the highest in the
      world, though in spite of this the prevalence of occult hepatitis B infection
      (OBI) is unknown. OBJECTIVES: This study was conducted with the aim to
      investigate the prevalence of OBI and frequency of isolated hepatitis B core
      antibody (anti-HBc alone) among antiretroviral (ART) naive HIV-positive patients
      in Mozambique. METHODS: A cross-sectional study was conducted in two health
      facilities within Maputo city. All ART-naive HIV seropositive patients attending
      outpatient clinics between June and October 2012 were consecutively enrolled.
      Blood samples were drawn from each participant and used for serological
      measurement of HBV surface antigen (HBsAg), antibodies against HBV surface
      antigen (anti-HBs) and antibodies against core antigen (anti-HBc) using ELISA.
      Quantification of HBV DNA was performed by real time PCR. A questionnaire was
      used to obtain demographics and clinical data. RESULTS: Of the 518 ART-naive HIV
      positive subjects enrolled in the study, 90.9% (471/518) were HBsAg negative.
      Among HBsAg negative, 45.2% (213/471) had isolated anti-HBc antibodies, and the
      frequency of OBI among patients with anti-HBc alone was 8.3% (17/206). OBI was
      not correlated either with CD4+ T cells count or transaminases levels. A total of
      11.8% of patients with OBI presented elevated HBV DNA level. Frequency of
      individuals with APRI score > 2 and FIB-4 score > 3.25 was higher in patients
      with OBI as compared not exposed, immune and anti-HBc alone patients. CONCLUSION:
      Our data demonstrate for the first time that OBI is prevalent among HIV patients
      in Mozambique, and will be missed using the commonly available serological assays
      that measures HBsAg.

PMID- 29320553
TI  - Undiagnosed abnormal postpartum blood loss: Incidence and risk factors.
AB  - BACKGROUND: We aimed to evaluate the incidence of undiagnosed abnormal postpartum
      blood loss (UPPBL) after vaginal delivery, identify the risk factors and compare
      them to those of postpartum haemorrhage (PPH). METHOD: The study population
      included women who participated in a randomized controlled trial of women with
      singleton low-risk pregnancy who delivered vaginally after 35 weeks' gestation (n
      = 3917). Clinical PPH was defined as postpartum blood loss >= 500 mL measured by
      using a collector bag and UPPBL was defined by a peripartum change in haemoglobin
      >= 2 g/dL in the absence of clinical PPH. Risk factors were assessed by
      multivariate multinomial logistic regression. RESULTS: The incidence of UPPBL and
      PPH was 11.2% and 11.0% of vaginal deliveries, respectively. The median
      peripartum change in Hb level was comparable between UPPBL and PPH groups (2.5
      g/dL interquartile range [2.2-3.0] and 2.4 g/dL IQR [1.5-3.3]). Risk factors
      specifically associated with UPPBL were Asian geographical origin (adjusted OR
      [aOR] 2.3, 95% confidence interval [CI] 1.2-4.2; p = 0.009), previous caesarean
      section (aOR 3.4, 2.1-5.5; p<0.001) and episiotomy (aOR 2.6, 1.8-3.6; p<0.001).
      Risk factors for both UPPBL and PPH were primiparity, long duration of labour,
      instrumental delivery and retained placenta. CONCLUSION: Undiagnosed abnormal
      postpartum blood loss is frequent among women giving birth vaginally and has
      specific risk factors. The clinical importance of this entity needs further
      confirmation, and the benefit of systematic or targeted prevention strategies
      needs to be assessed.

PMID- 29320554
TI  - A census of P. longum's phytochemicals and their network pharmacological
      evaluation for identifying novel drug-like molecules against various diseases,
      with a special focus on neurological disorders.
AB  - Piper longum (P. longum, also called as long pepper) is one of the common
      culinary herbs that has been extensively used as a crucial constituent in various
      indigenous medicines, specifically in traditional Indian medicinal system known
      as Ayurveda. For exploring the comprehensive effect of its constituents in humans
      at proteomic and metabolic levels, we have reviewed all of its known
      phytochemicals and enquired about their regulatory potential against various
      protein targets by developing high-confidence tripartite networks consisting of
      phytochemical-protein target-disease association. We have also (i) studied
      immunomodulatory potency of this herb; (ii) developed subnetwork of human PPI
      regulated by its phytochemicals and could successfully associate its specific
      modules playing important role in diseases, and (iii) reported several novel drug
      targets. P10636 (microtubule-associated protein tau, that is involved in diseases
      like dementia etc.) was found to be the commonly screened target by about seventy
      percent of these phytochemicals. We report 20 drug-like phytochemicals in this
      herb, out of which 7 are found to be the potential regulators of 5 FDA approved
      drug targets. Multi-targeting capacity of 3 phytochemicals involved in
      neuroactive ligand receptor interaction pathway was further explored via
      molecular docking experiments. To investigate the molecular mechanism of P.
      longum's action against neurological disorders, we have developed a computational
      framework that can be easily extended to explore its healing potential against
      other diseases and can also be applied to scrutinize other indigenous herbs for
      drug-design studies.

PMID- 29320555
TI  - Chronic kidney disease associated with decreased bone mineral density, uric acid
      and metabolic syndrome.
AB  - OBJECTIVE: The relationship between decreased bone mineral density (BMD) and
      chronic kidney disease (CKD) is controversial. The associations among metabolic
      syndrome (MetS), serum uric acid and CKD are also unclear. We aimed to
      investigate the relationship between decreased BMD, MetS, serum uric acid and CKD
      in a general population. METHODS: A total of 802 subjects who visited a medical
      center in Southern Taiwan and underwent a BMD measured by dual-energy X-ray
      absorptiometry (DEXA) during a health examination were enrolled in this
      retrospective cross-sectional study. Either osteopenia or osteoporosis was
      defined as decreased BMD. CKD was defined as the estimated glomerular filtration
      rate (eGFR) of less than 60 mL/min/1.73m2. Simple and multivariate logistic
      regression analyses were used to investigate the association between variables,
      decreased BMD and CKD. RESULTS: Of the 802 subjects with a mean age of 54.4+/
      10.2 years, the prevalence of decreased BMD was 62.9%, and CKD was 3.7%. Simple
      logistic analysis showed that sex (OR 3.50, 95% CI 1.21-10.12, p = 0.021), age
      (OR 1.14, 95% CI 1.07-1.21, p<0.001), BMI (OR 1.11, 95% CI 1.01-1.22, p = 0.028),
      waist circumference (OR 1.06, 95% CI 1.02-1.10, p = 0.002), SBP (OR 1.03, 95% CI
      1.01-1.04, p = 0.003), DBP (OR 1.03, 95% CI 1.00-1.06, p = 0.030), HDL-C (OR
      0.97, 95% CI 0.94-1.00, p = 0.026), uric acid (OR 1.84, 95% CI 1.49-2.27,
      p<0.001), metabolic syndrome (OR 2.68, 95% CI 1.29-5.67, p = 0.009), and
      decreased BMD (OR 3.998, 95% CI 1.38-11.57, p = 0.011) were significantly
      associated with CKD. Multivariate analysis showed that age (OR 1.05, 95% CI 1.03
      1.07, p<0.001), decreased BMD (OR 0.64, 95% CI 0.45-0.91, p = 0.013), and uric
      acid (OR 1.40, 95% CI 1.24-1.59, p<0.001) were significantly independently
      associated with CKD. CONCLUSIONS: Decreased BMD, uric acid and MetS were
      significantly associated with CKD.. Further large and prospective cohort studies
      are necessary to investigate whether management of osteoporosis, hyperuricemia,
      or MetS might prevent the progression of CKD.

PMID- 29320556
TI  - Care-seeking patterns among families that experienced under-five child mortality
      in rural Rwanda.
AB  - BACKGROUND: Over half of under-five deaths occur in sub-Saharan Africa and
      appropriate, timely, quality care is critical for saving children's lives. This
      study describes the context surrounding children's deaths from the time the
      illness was first noticed, through the care-seeking patterns leading up to the
      child's death, and identifies factors associated with care-seeking for these
      children in rural Rwanda. METHODS: Secondary analysis of a verbal and social
      autopsy study of caregivers who reported the death of a child between March 2013
      to February 2014 that occurred after discharge from the child's birth facility in
      southern Kayonza and Kirehe districts in Rwanda. Bivariate analyses using
      Fisher's exact tests were conducted to identify child, caregiver, and household
      factors associated with care-seeking from the formal health system (i.e.,
      community health worker or health facility). Factors significant at alpha = 0.10
      significance level were considered for backwards stepwise multivariate logistic
      regression, stopping when remaining factors were significantly associated with
      care-seeking at alpha = 0.05 significance level. RESULTS: Among the 516 eligible
      deaths among children under-five, 22.7% (n = 117) did not seek care from the
      health system. For those who did, the most common first point of contact was
      community health workers (45.8%). In multivariate logistic regression, higher
      maternal education (OR = 3.36, 95% CI: 1.89, 5.98), having diarrhea (OR = 4.21,
      95%CI: 1.95, 9.07) or fever (OR = 2.03, 95%CI: 1.11, 3.72), full household
      insurance coverage (3.48, 95%CI: 1.79, 6.76), and longer duration of illness (OR
      = 22.19, 95%CI: 8.88, 55.48) were significantly associated with formal care
      seeking. CONCLUSION: Interventions such as community health workers and insurance
      promote access to care, however a gap remains as many children had no contact
      with the health system prior to death and those who sought formal care still
      died. Further efforts are needed to respond to urgent cases in communities and
      further understand remaining barriers to accessing appropriate, quality care.

PMID- 29320557
TI  - High AHR expression in breast tumors correlates with expression of genes from
      several signaling pathways namely inflammation and endogenous tryptophan
      metabolism.
AB  - Increasing epidemiological and animal experimental data provide substantial
      support for the role of aryl hydrocarbon receptor (AhR) in mammary tumorigenesis.
      The effects of AhR have been clearly demonstrated in rodent models of breast
      carcinogenesis and in several established human breast cancer cell lines
      following exposure to AhR ligands or AhR overexpression. However, relatively
      little is known about the role of AhR in human breast cancers. AhR has always
      been considered to be a regulator of toxic and carcinogenic responses to
      environmental contaminants such as TCDD (dioxin) and benzo[a]pyrene (BaP). The
      aim of this study was to identify the type of breast tumors (ERalpha-positive or
      ERalpha-negative) that express AHR and how AhR affects human tumorigenesis. The
      levels of AHR, AHR nuclear translocator (ARNT) and AHR repressor (AHRR) mRNA
      expression were analyzed in a cohort of 439 breast tumors, demonstrating a weak
      association between high AHR expression and age greater than fifty years and
      ERalpha-negative status, and HR-/ERBB2 breast cancer subtypes. AHRR mRNA
      expression was associated with metastasis-free survival, while AHR mRNA
      expression was not. Immunohistochemistry revealed the presence of AhR protein in
      both tumor cells (nucleus and/or cytoplasm) and the tumor microenvironment
      (including endothelial cells and lymphocytes). High AHR expression was correlated
      with high expression of several genes involved in signaling pathways related to
      inflammation (IL1B, IL6, TNF, IL8 and CXCR4), metabolism (IDO1 and TDO2 from the
      kynurenine pathway), invasion (MMP1, MMP2 and PLAU), and IGF signaling (IGF2R,
      IGF1R and TGFB1). Two well-known ligands for AHR (TCDD and BaP) induced mRNA
      expression of IL1B and IL6 in an ERalpha-negative breast tumor cell line. The
      breast cancer ER status likely influences AhR activity involved in these
      signaling pathways. The mechanisms involved in AhR activation and target gene
      expression in breast cancers are also discussed.

PMID- 29320558
TI  - Thrombolysis in stroke patients: Comparability of point-of-care versus central
      laboratory international normalized ratio.
AB  - BACKGROUND: In acute stroke patients, thrombolysis is one gold standard therapy
      option within the first four hours after the ischemic event. A contraindication
      for thrombolysis is an International Normalized Ratio (INR) value >1.7. Since
      time is brain, rapid and reliable INR results are fundamental. Aim was to compare
      INR values determined by central laboratory (CL) analyzer and Point-of-Care
      Testing(POCT)-device and to evaluate the quality of POCT performance in cases of
      potential therapeutic thrombolysis at a certified stroke unit. METHODS: In 153
      patients INR measurements using POCT-devices (HEMOCHRON Signature Elite(r)) were
      compared to INR measurements (BCS(r)XP) performed at the central laboratory.
      Outlier evaluation was performed regarding the critical thrombolysis cut-off.
      RESULTS: Overall, we demonstrated a significant correlation (r = 0.809, p<0.0001)
      between both measurement methods. Mean value of the absolute difference between
      CL-INR and POCT-INR measurements was 0.23. In 95.4% of these cases, no
      differences regarding the critical cut-off (INR 1.7) were observed. POCT-INR
      values tended to be higher than the CL-INR values (p = 0.01). In 4.6% cases, a
      different value regarding thrombolysis cut-off was found. All patients were >75
      years. CONCLUSIONS: POCT-INR measurements based on our POCT concept are suitable
      to determine INR values in critical stroke patients. Nevertheless, outlier
      evaluation is mandatory.

PMID- 29320559
TI  - Characterization of the naive murine antibody repertoire using unamplified high
      throughput sequencing.
AB  - Antibody specificity and diversity are generated through the enzymatic splicing
      of genomic gene segments within each B cell. Antibodies are heterodimers of heavy
      and light-chains encoded on separate loci. We studied the antibody repertoire
      from pooled, splenic tissue of unimmunized, adult female C57BL/6J mice, using
      high-throughput sequencing (HTS) without amplification of antibody transcripts.
      We recovered over 90,000 heavy-chain and over 135,000 light-chain immunoglobulin
      sequences. Individual V-, D-, and J-gene segment usage was uniform among the
      three mouse pools, particularly in highly abundant gene segments, with low
      frequency V-gene segments not being detected in all pools. Despite the similar
      usage of individual gene segments, the repertoire of individual B-cell CDR3 amino
      acid sequences in each mouse pool was highly varied, affirming the combinatorial
      diversity in the B-cell pool that has been previously demonstrated. There also
      was some skewing in the V-gene segments that were detected depending on
      chromosomal location. This study presents a unique, non-primer biased glimpse of
      the conventionally housed, unimmunized antibody repertoire of the C57BL6/J mouse.

PMID- 29320560
TI  - Measurements agreement between low-cost and high-level handheld 3D scanners to
      scan the knee for designing a 3D printed knee brace.
AB  - Use of additive manufacturing is growing rapidly in the orthotics field. This
      technology allows orthotics to be designed directly on digital scans of limbs.
      However, little information is available about scanners and 3D scans. The aim of
      this study is to look at the agreement between manual measurements, high-level
      and low-cost handheld 3D scanners. We took two manual measurements and three 3D
      scans with each scanner from 14 lower limbs. The lower limbs were divided into 17
      sections of 30mm each from 180mm above the mid-patella to 300mm below. Time to
      record and to process the three 3D scans for scanners methods were compared with
      Student t-test while Bland-Altman plots were used to study agreement between
      circumferences of each section from the three methods. The record time was 97s
      shorter with high-level scanner than with the low-cost (p = .02) while the
      process time was nine times quicker with the low-cost scanner (p < .01). An
      overestimation of 2.5mm was found in high-level scanner compared to manual
      measurement, but with a better repeatability between measurements. The low-cost
      scanner tended to overestimate the circumferences from 0.1% to 1.5%,
      overestimation being greater for smaller circumferences. In conclusion, 3D
      scanners provide more information about the shape of the lower limb, but the
      reliability depends on the 3D scanner and the size of the scanned segment. Low
      cost scanners could be useful for clinicians because of the simple and fast
      process, but attention should be focused on accuracy, which depends on the
      scanned body segment.

PMID- 29320561
TI  - alpha-smooth muscle actin is not a marker of fibrogenic cell activity in skeletal
      muscle fibrosis.
AB  - alpha-Smooth muscle actin (alpha-SMA) is used as a marker for a subset of
      activated fibrogenic cells, myofibroblasts, which are regarded as important
      effector cells of tissue fibrogenesis. We address whether alpha-SMA-expressing
      myofibroblasts are detectable in fibrotic muscles of mdx5cv mice, a mouse model
      for Duchenne muscular dystrophy (DMD), and whether the alpha-SMA expression
      correlates with the fibrogenic function of intramuscular fibrogenic cells. alpha
      SMA immunostaining signal was not detected in collagen I (GFP)-expressing cells
      in fibrotic muscles of ColI-GFP/mdx5cv mice, but it was readily detected in
      smooth muscle cells lining intramuscular blood vessel walls. alpha-SMA expression
      was detected by quantitative RT-PCR and Western blot in fibrogenic cells sorted
      from diaphragm and quadriceps muscles of the ColI-GFP/mdx5cv mice. Consistent
      with the more severe fibrosis in the ColI-GFP/mdx5cv diaphragm, the fibrogenic
      cells in the diaphragm exerted a stronger fibrogenic function than the fibrogenic
      cells in the quadriceps as gauged by their extracellular matrix gene expression.
      However, both gene and protein expression of alpha-SMA was lower in the diaphragm
      fibrogenic cells than in the quadriceps fibrogenic cells in the ColI-GFP/mdx5cv
      mice. We conclude that myofibroblasts are present in fibrotic skeletal muscles,
      but their expression of alpha-SMA is not detectable by immunostaining. The level
      of alpha-SMA expression by intramuscular fibrogenic cells does not correlate
      positively with the level of collagen gene expression or the severity of skeletal
      muscle fibrosis in the mdx5cv mice. alpha-SMA is not a functional marker of
      fibrogenic cells in skeletal muscle fibrosis associated with muscular dystrophy.

PMID- 29320562
TI  - M1-like macrophages change tumor blood vessels and microenvironment in murine
      melanoma.
AB  - Tumor-associated macrophages (TAMs) play a significant role in at least two key
      processes underlying neoplastic progression: angiogenesis and immune
      surveillance. TAMs phenotypic changes play important role in tumor vessel
      abnormalization/ normalization. M2-like TAMs stimulate immunosuppression and
      formation of defective tumor blood vessels leading to tumor progression. In
      contrast M1-like TAMs trigger immune response and normalize irregular tumor
      vascular network which should sensitize cancer cells to chemo- and radiotherapy
      and lead to tumor growth regression. Here, we demonstrated that combination of
      endoglin-based DNA vaccine with interleukin 12 repolarizes TAMs from tumor growth
      promoting M2-like phenotype to tumor growth-inhibiting M1-like phenotype.
      Combined therapy enhances tumor infiltration by CD4+, CD8+ lymphocytes and NK
      cells. Depletion of TAMs as well as CD8+ lymphocytes and NK cells, but not CD4+
      lymphocytes, reduces the effect of combined therapy. Furthermore, combined
      therapy improves tumor vessel maturation, perfusion and reduces hypoxia. It
      caused that suboptimal doses of doxorubicin reduced the growth of tumors in mice
      treated with combined therapy. To summarize, combination of antiangiogenic drug
      and immunostimulatory agent repolarizes TAMs phenotype from M2-like (pro-tumor)
      into M1-like (anti-tumor) which affects the structure of tumor blood vessels,
      improves the effect of chemotherapy and leads to tumor growth regression.

PMID- 29320564
TI  - A time-lagged effect of conspecific density on habitat selection by snowshoe
      hare.
AB  - Ideal free distribution theory predicts that increased conspecific density
      redistributes individuals to low-density, suboptimal habitat. However, possible
      lags in response to population density remain poorly documented. Snowshoe hares
      (Lepus americanus) may exhibit density-dependent habitat selection due to its
      marked variation in population density. Based on 11 years (2004-2014) of snow
      tracking in Quebec (Canada), we investigated snowshoe hares' short-term and
      delayed habitat selection responses to population density. We predicted that at
      high densities, hare distribution expands into low-density habitat, thus
      weakening the association between hares and high-density habitat. We surveyed
      hare tracks along 95 km of transects on average each year and georeferenced
      14,240 tracks. We used Generalized Estimating Equations for track count per 100 m
      transect segment as a function of the proportion of different forest age classes
      (0-20 y, 20-40 y and 40-80 y) within 50 m of the segments. We used model
      coefficients for each age class as a measure of habitat preference, and modeled
      those coefficients as a function of a population density index in current and
      previous winters. Coefficients for 20- to 40-y-old forests were positive each
      year, indicating that this habitat was preferred. The association between track
      counts and 20- to 40-y-old forest significantly declined with density during the
      previous winter, suggesting that hare spread from preferred forest with a lagged
      response to density. To our knowledge, no previous empirical studies have
      documented a lagged habitat selection response to population density. Time lags
      offer possible explanation for documented deviations from ideal free distribution
      models.

PMID- 29320563
TI  - Field effectiveness of highly pathogenic avian influenza H5N1 vaccination in
      commercial layers in Indonesia.
AB  - Although vaccination of poultry for control of highly pathogenic avian influenza
      virus (HPAIV) H5N1 has been practiced during the last decade in several
      countries, its effectiveness under field conditions remains largely unquantified.
      Effective HPAI vaccination is however essential in preventing incursions, silent
      infections and generation of new H5N1 antigenic variants. The objective of this
      study was to asses the level and duration of vaccine induced immunity in
      commercial layers in Indonesia. Titres of H5N1 haemagglutination inhibition (HI)
      antibodies were followed in individual birds from sixteen flocks, age 18-68 week
      old (wo). The study revealed that H5N1 vaccination had highly variable outcome,
      including vaccination failures, and was largely ineffective in providing long
      lasting protective immunity. Flocks were vaccinated with seven different
      vaccines, administer at various times that could be grouped into three regimes:
      In regime A, flocks (n = 8) were vaccinated two or three times before 19 wo; in
      regime B (n = 2), two times before and once after 19 wo; and in regime C (n = 6)
      three to four times before and two to three times after 19 wo. HI titres in
      regime C birds were significantly higher during the entire observation period in
      comparison to titres of regime A or B birds, which also differed significantly
      from each other. The HI titres of individual birds in each flock differed
      significantly from birds in other flocks, indicating that the effectiveness of
      field vaccination was highly variable and farm related. Protective HI titres of
      >4log2, were present in the majority of flocks at 18 wo, declined thereafter at
      variable rate and only two regime C flocks had protective HI titres at 68 wo.
      Laboratory challenge with HPAIV H5N1 of birds from regime A and C flocks
      confirmed that protective immunity differed significantly between flocks
      vaccinated by these two regimes. The study revealed that effectiveness of the
      currently applied H5N1 vaccination could be improved and measures to achieve this
      are discussed.

PMID- 29320565
TI  - The absence of N-acetylglucosamine in wall teichoic acids of Listeria
      monocytogenes modifies biofilm architecture and tolerance to rinsing and cleaning
      procedures.
AB  - The wall teichoic acid (WTA) is the major carbohydrate found within the
      extracellular matrix of the Listeria monocytogenes biofilm. We first addressed
      the frequency of spontaneous mutations in two genes (lmo2549 and lmo2550)
      responsible for the GlcNAcylation in 93 serotype 1/2a strains that were mainly
      isolated from seafood industries. We studied the impact of mutations in lmo2549
      or lmo2550 genes on biofilm formation by using one mutant carrying a natural
      mutation inactivating the lmo2550 gene (DSS 1130 BFA2 strain) and two EGD-e
      mutants that lack respective genes by in-frame deletion of lmo2549 or lmo2550
      using splicing-by-overlap-extension PCR, followed by allelic exchange
      mutagenesis. The lmo2550 gene mutation, occurring in around 50% isolates, caused
      a decrease in bacterial adhesion to stainless steel compared to wild-type EGD-e
      strain during the adhesion step. On the other hand, bacterial population weren't
      significantly different after 24h-biofilm formation. The biofilm architecture was
      different between the wild-type strain and the two mutants inactivated for
      lmo2549 or lmo2550 genes respectively with the presence of bacterial micro
      colonies for mutants which were not observed in the wild-type EGD-e strain
      biofilm. These differences might account for the stronger hydrophilic surface
      exhibited by the mutant cells. Upon a water flow or to a cleaning procedure at a
      shear stress of 0.16 Pa, the mutant biofilms showed the higher detachment rate
      compared to wild-type strain. Meanwhile, an increase in the amount of residual
      viable but non-culturable population on stainless steel was recorded in two
      mutants. Our data suggests that the GlcNAc residue of WTA played a role in
      adhesion and biofilm formation of Listeria monocyctogenes.

PMID- 29320566
TI  - The effect of time-of-day and chest physiotherapy on multiple breath washout
      measures in children with clinically stable cystic fibrosis.
AB  - BACKGROUND: In this pilot study we investigated daytime variation of multiple
      breath nitrogen washout (N2MBW) measures in children with clinically stable
      cystic fibrosis. To our knowledge the effect of time-of-day on multiple breath
      washout measures in patients with cystic fibrosis has not previously been
      reported. Furthermore, we assessed the influence of chest physiotherapy on N2MBW
      measures. METHODS: Ten school children with cystic fibrosis performed N2MBW
      followed by spirometry and plethysmography in the morning and afternoon at three
      visits that were one month apart. Chest physiotherapy was performed immediately
      before the afternoon measurements at visit 2 and immediately before morning and
      afternoon measurements at visit 3. The influence of time-of-day and chest
      physiotherapy on the measures was evaluated using linear mixed models. RESULTS:
      There were adequate quality data from 8 children with median age (range) 9.6
      (6.0; 15.1) years. Baseline lung clearance index (LCI) (range) was 9.0 (7.1;
      13.0) and baseline FEV1% predicted was 97.5 (78.5; 117.9). No N2MBW measures were
      significantly influenced by time-of-day or chest physiotherapy. LCI (95%
      confidence interval) decreased non-significantly 0.05 (-0.32; 0.22) during the
      day and increased non-significantly 0.08 (-0.26; 0.42) after chest physiotherapy.
      All spirometric measures were unaffected by time-of-day and chest physiotherapy.
      For plethysmographic measures FRCpleth decreased significantly (p<0.01) 110 mL
      during the day, whereas a borderline significant (p = 0.046) decrease in
      DeltaFRCpleth-MBW during the day and a borderline significant (p = 0.03) increase
      in TLC after CPT were observed. CONCLUSION: This study demonstrated that the time
      of-day as well as chest physiotherapy performed immediately prior to N2MBW had no
      consistent or significant influence on N2MBW measures. However, we emphasize that
      further studies of the effect of both daytime variation and the effect of chest
      physiotherapy on multiple breath washout measures are warranted.

PMID- 29320567
TI  - Myocardium of patients with dilated cardiomyopathy presents altered expression of
      genes involved in thyroid hormone biosynthesis.
AB  - BACKGROUND: The association between dilated cardiomyopathy (DCM) and low thyroid
      hormone (TH) levels has been previously described. In these patients abnormal
      thyroid function is significantly related to impaired left ventricular (LV)
      function and increased risk of death. Although TH was originally thought to be
      produced exclusively by the thyroid gland, we recently reported TH biosynthesis
      in the human ischemic heart. OBJECTIVES: Based on these findings, we evaluated
      whether the genes required for TH production are also altered in patients with
      DCM. METHODS: Twenty-three LV tissue samples were obtained from patients with DCM
      (n = 13) undergoing heart transplantation and control donors (n = 10), and used
      for RNA sequencing analysis. The number of LV DCM samples was increased to 23 to
      determine total T4 and T3 tissue levels by ELISA. RESULTS: We found that all
      components of TH biosynthesis are expressed in human dilated heart tissue.
      Expression of genes encoding thyroperoxidase (-2.57-fold, P < 0.05) and dual
      oxidase 2 (2.64-fold, P < 0.01), the main enzymatic system of TH production, was
      significantly altered in patients with DCM and significantly associated with LV
      remodeling parameters. Thyroxine (T4) cardiac tissue levels were significantly
      increased (P < 0.01), whilst triiodothyronine (T3) levels were significantly
      diminished (P < 0.05) in the patients. CONCLUSIONS: Expression of TH biosynthesis
      machinery in the heart and total tissue levels of T4 and T3, are altered in
      patients with DCM. Given the relevance of TH in cardiac pathology, our results
      provide a basis for new gene-based therapeutic strategies for treating DCM.

PMID- 29320568
TI  - Gastrointestinal safety of etoricoxib in osteoarthritis and rheumatoid arthritis:
      A meta-analysis.
AB  - OBJECTIVE: To ascertain if etoricoxib increases the risk of gastrointestinal
      adverse events (GAEs) compared with placebo, diclofenac, and naproxen in the
      treatment of patients with osteoarthritis (OA) or rheumatoid arthritis (RA).
      METHODS: Studies were searched in MEDLINE, EMBASE, Cochrane Central Register of
      Controlled Trials from inception to August 2017. Randomized Clinical Trials
      (RCTs) that compared etoricoxib with placebo and other active drug for patients
      with OA or RA and reported data on gastrointestinal safety (which is of interest
      to patients and clinicians) were included. The follow-up time window for GAEs was
      defined as within 28 days subsequent to the last dose of study medication. A meta
      analysis was conducted using a fixed-effect model. Risk ratios (RRs) and 95%
      confidence intervals (CIs) were measured. RESULTS: We found nine randomized
      clinical trials (RCTs) that included information on gastrointestinal safety
      during follow-up time. Among them, five RCTs compared etoricoxib with placebo,
      four RCTs compared etoricoxib with diclofenac, and three RCTs compared etoricoxib
      with naproxen. Etoricoxib did not increase the risk of GAEs compared with
      placebo. Compared with diclofenac and naproxen, etoricoxib reduced the GAE risk
      (RR, 0.67; 95% CI, 0.59-0.76; p < 0.00001; 0.59; 0.48-0.72; < 0.00001) during
      follow-up time. CONCLUSIONS: In patients with OA or RA, etoricoxib did not
      increase the GAE risk compared with placebo, but reduced the GAE risk effectively
      compared with diclofenac and naproxen during follow-up time.

PMID- 29320569
TI  - Transcriptome profiling of pumpkin (Cucurbita moschata Duch.) leaves infected
      with powdery mildew.
AB  - Cucurbit powdery mildew (PM) is one of the most severe fungal diseases, but the
      molecular mechanisms underlying PM resistance remain largely unknown, especially
      in pumpkin (Cucurbita moschata Duch.). The goal of this study was to identify
      gene expression differences in PM-treated plants (harvested at 24 h and 48 h
      after inoculation) and untreated (control) plants of inbred line "112-2" using
      RNA sequencing (RNA-Seq). The inbred line "112-2" has been purified over 8
      consecutive generations of self-pollination and shows high resistance to PM. More
      than 7600 transcripts were examined in pumpkin leaves, and 3129 and 3080
      differentially expressed genes (DEGs) were identified in inbred line "112-2" at
      24 and 48 hours post inoculation (hpi), respectively. Based on the KEGG (Kyoto
      Encyclopedia of Genes and Genomes) pathway database and GO (Gene Ontology)
      database, a complex regulatory network for PM resistance that may involve hormone
      signal transduction pathways, transcription factors and defense responses was
      revealed at the transcription level. In addition, the expression profiles of 16
      selected genes were analyzed using quantitative RT-PCR. Among these genes, the
      transcript levels of 6 DEGs, including bHLH87 (Basic Helix-loop-helix
      transcription factor), ERF014 (Ethylene response factor), WRKY21 (WRKY domain),
      HSF (heat stress transcription factor A), MLO3 (Mildew Locus O), and SGT1
      (Suppressor of G-Two Allele of Skp1), in PM-resistant "112-2" were found to be
      significantly up- or down-regulated both before 9 hpi and at 24 hpi or 48 hpi;
      this behavior differed from that observed in the PM-susceptible material
      (cultivar "Jiujiangjiaoding"). The transcriptome data provide novel insights into
      the response of Cucurbita moschata to PM stress and are expected to be highly
      useful for dissecting PM defense mechanisms in this major vegetable and for
      improving pumpkin breeding with enhanced resistance to PM.

PMID- 29320570
TI  - Image-guided, whole-pelvic, intensity-modulated radiotherapy for biochemical
      recurrence following radical prostatectomy in high-risk prostate cancer patients.
AB  - BACKGROUND: The optimal field size of salvage radiotherapy (SRT) for biochemical
      recurrence, particularly for patients with high-risk prostate cancer, remains
      undefined. This retrospective analysis was performed to investigate oncological
      outcomes as well as treatment-related toxicity following salvage intensity
      modulated radiotherapy (IMRT) to the whole pelvis and to compare the results with
      other studies implementing a small field size of the prostate bed. METHODS: The
      medical records of 170 patients with high-risk prostate cancer who received SRT
      for biochemical recurrence following prostatectomy were reviewed. Whole-pelvic
      IMRT was administered with a median dose of 66 Gy in 30 fractions. To improve
      treatment accuracy, an endorectal balloon device and daily cone-beam computed
      tomography were utilized. Androgen-deprivation therapy combined with SRT was
      administered to 97 (57.1%) patients. RESULTS: Eventually, 68 (40.0%) patients
      showed biochemical progression (BCP) after SRT. With a median follow-up period of
      56 months, the 5-year BCP-free survival was 38.6%. The overall and cause-specific
      survival rates were 90.9% and 96.7%, respectively. Regarding BCP-free survival
      analysis, pathological T stage, persistent prostate-specific antigen (PSA)
      elevation after prostatectomy, and preSRT PSA level were significant prognostic
      factors on univariate analysis. On multivariate analysis, pathological T stage
      and preSRT PSA value retained their significance. Acute and late grade-3
      genitourinary toxicities were observed in one (0.6%) and five (2.9%) patients,
      respectively. One patient each developed acute and late grade-3 gastrointestinal
      toxicity. CONCLUSION: SRT to whole pelvis using IMRT and image guidance is as
      safe as SRT to the prostate bed, but its efficacy should be confirmed in ongoing
      randomized trials. PreSRT PSA was the only controllable prognostic factor,
      suggesting the benefit of early SRT.

PMID- 29320571
TI  - Inhibitory effect and possible mechanism of a Pseudomonas strain QBA5 against
      gray mold on tomato leaves and fruits caused by Botrytis cinerea.
AB  - The fungal pathogen Botrytis cinerea causes gray mold disease on various hosts,
      which results in serious economic losses. Over the past several decades, many
      kinds of fungicides have been used to successfully control the disease.
      Meanwhile, the uses of fungicides lead to environmental pollution as well as a
      potential threat to the human health by the chemical residues in tomato fruit.
      Also, the gray mold disease is difficult to control with fungicides. Therefore,
      exploring alternative measures such as biological controls could be the best
      choice to control the disease and alleviate damages caused by fungicides. In this
      study, we isolated and identified a novel Pseudomonas strain termed as QBA5 from
      healthy tomato plant based on the morphological, biochemical characteristics and
      molecular detection. The antifungal activity assays revealed that, in the
      presence of QBA5, conidia germination, germ tube elongation and mycelial growth
      of B. cinerea were significantly inhibited. Most importantly, QBA5 exerted a
      significant preventive effectiveness against gray mold on tomato fruits and
      plants. The possible mechanism of QBA5 involved in the inhibition of B. cinerea
      was investigated. It revealed that the conidia plasma membrane of B. cinerea was
      severely damaged by QBA5. Further, four different antifungal compounds in the
      supernatant of QBA5 were separated by preparative high performance liquid
      chromatography (PHPLC). Overall, the data indicate that there is a considerable
      potential for QBA5 to reduce the damage caused by gray mold disease on tomato.

PMID- 29320572
TI  - International migration patterns of Red-throated Loons (Gavia stellata) from four
      breeding populations in Alaska.
AB  - Identifying post-breeding migration and wintering distributions of migratory
      birds is important for understanding factors that may drive population dynamics.
      Red-throated Loons (Gavia stellata) are widely distributed across Alaska and
      currently have varying population trends, including some populations with recent
      periods of decline. To investigate population differentiation and the location of
      migration pathways and wintering areas, which may inform population trend
      patterns, we used satellite transmitters (n = 32) to describe migration patterns
      of four geographically separate breeding populations of Red-throated Loons in
      Alaska. On average (+/- SD) Red-throated Loons underwent long (6,288 +/- 1,825
      km) fall and spring migrations predominantly along coastlines. The most northern
      population (Arctic Coastal Plain) migrated westward to East Asia and traveled
      approximately 2,000 km farther to wintering sites than the three more southerly
      populations (Seward Peninsula, Yukon-Kuskokwim Delta, and Copper River Delta)
      which migrated south along the Pacific coast of North America. These migration
      paths are consistent with the hypothesis that Red-throated Loons from the Arctic
      Coastal Plain are exposed to contaminants in East Asia. The three more southerly
      breeding populations demonstrated a chain migration pattern in which the more
      northerly breeding populations generally wintered in more northerly latitudes.
      Collectively, the migration paths observed in this study demonstrate that some
      geographically distinct breeding populations overlap in wintering distribution
      while others use highly different wintering areas. Red-throated Loon population
      trends in Alaska may therefore be driven by a wide range of effects throughout
      the annual cycle.

PMID- 29320573
TI  - An evaluation of three-dimensional photogrammetric and morphometric techniques
      for estimating volume and mass in Weddell seals Leptonychotes weddellii.
AB  - Body mass dynamics of animals can indicate critical associations between
      extrinsic factors and population vital rates. Photogrammetry can be used to
      estimate mass of individuals in species whose life histories make it logistically
      difficult to obtain direct body mass measurements. Such studies typically use
      equations to relate volume estimates from photogrammetry to mass; however, most
      fail to identify the sources of error between the estimated and actual mass. Our
      objective was to identify the sources of error that prevent photogrammetric mass
      estimation from directly predicting actual mass, and develop a methodology to
      correct this issue. To do this, we obtained mass, body measurements, and scaled
      photos for 56 sedated Weddell seals (Leptonychotes weddellii). After creating a
      three-dimensional silhouette in the image processing program PhotoModeler Pro, we
      used horizontal scale bars to define the ground plane, then removed the below
      ground portion of the animal's estimated silhouette. We then re-calculated body
      volume and applied an expected density to estimate animal mass. We compared the
      body mass estimates derived from this silhouette slice method with estimates
      derived from two other published methodologies: body mass calculated using
      photogrammetry coupled with a species-specific correction factor, and estimates
      using elliptical cones and measured tissue densities. The estimated mass values
      (mean +/- standard deviation 345+/-71 kg for correction equation, 346+/-75 kg for
      silhouette slice, 343+/-76 kg for cones) were not statistically distinguishable
      from each other or from actual mass (346+/-73 kg) (ANOVA with Tukey HSD post-hoc,
      p>0.05 for all pairwise comparisons). We conclude that volume overestimates from
      photogrammetry are likely due to the inability of photo modeling software to
      properly render the ventral surface of the animal where it contacts the ground.
      Due to logistical differences between the "correction equation", "silhouette
      slicing", and "cones" approaches, researchers may find one technique more useful
      for certain study programs. In combination or exclusively, these three
      dimensional mass estimation techniques have great utility in field studies with
      repeated measures sampling designs or where logistic constraints preclude
      weighing animals.

PMID- 29320574
TI  - Acceleration of small bowel motility after oral administration of dai-kenchu-to
      (TJ-100) assessed by cine magnetic resonance imaging.
AB  - Dai-kenchu-to (TJ-100) is an herbal medicine used to shorten the duration of
      intestinal transit by accelerating intestinal movement. However, intestinal
      movement in itself has not been evaluated in healthy volunteers using
      radiography, fluoroscopy, and radioisotopes because of exposure to ionizing
      radiation. The purpose of this study was to evaluate the effect of TJ-100 on
      intestinal motility using cinematic magnetic resonance imaging (cine MRI) with a
      steady-state free precession sequence. Ten healthy male volunteers received 5 g
      of either TJ-100 or lactose without disclosure of the identity of the substance.
      Each volunteer underwent two MRI examinations after taking the substances (TJ-100
      and lactose) on separate days. They drank 1200 mL of tap water and underwent cine
      MRI after 10 min. A steady-state free precession sequence was used for imaging,
      which was performed thrice at 0, 10, 20, 30, 40, and 50 min. The bowel
      contraction frequency and distention score were assessed. Wilcoxon signed-rank
      test was used, and differences were considered significant at a P-value <0.05.
      The bowel contraction frequency tended to be greater in the TJ-100 group and was
      significantly different in the ileum at 20 (TJ-100, 8.95 +/- 2.88; lactose, 4.80
      +/- 2.92; P < 0.05) and 50 min (TJ-100, 9.45 +/- 4.49; lactose, 4.45 +/- 2.65; P
      < 0.05) between the groups. No significant differences were observed in the bowel
      distention scores. Cine MRI demonstrated that TJ-100 activated intestinal
      motility without dependence on ileum distention.

PMID- 29320575
TI  - AZP-531, an unacylated ghrelin analog, improves food-related behavior in patients
      with Prader-Willi syndrome: A randomized placebo-controlled trial.
AB  - CONTEXT AND OBJECTIVE: Prader-Willi syndrome (PWS) is characterized by early
      onset hyperphagia and increased circulating levels of the orexigenic Acylated
      Ghrelin (AG) hormone with a relative deficit of Unacylated Ghrelin (UAG). AZP
      531, a first-in-class UAG analog, was shown to inhibit the orexigenic effect of
      AG in animals, to improve glycemic control and decrease body weight in humans. We
      aimed to investigate the safety and efficacy of AZP-531 in patients with PWS for
      whom no approved treatment for hyperphagia is currently available. METHODS AND
      DESIGN: Multi-center, randomized, double-blind, placebo-controlled trial. Forty
      seven patients with genetically confirmed PWS and evidence of hyperphagia
      received daily subcutaneous injections of AZP-531 (3 and 4 mg for 50-70 kg and
      >70 kg body weight, respectively) or matching placebo for 14 days. Assessments
      included adverse events, vital signs, safety laboratory tests, the Hyperphagia
      Questionnaire (HQ), patient-reported appetite, body composition and glycemic
      measures. RESULTS: AZP-531 was well tolerated. There was a significant
      improvement with AZP-531 versus placebo in the mean total score, the 9-item score
      and the severity domain score of the HQ (p < .05). The highest reduction in the
      total and 9-item scores was observed in AZP-531 subjects with the highest
      hyperphagia score at baseline. Findings were supported by a reduction in appetite
      scores observed with AZP-531 only. Body weight did not change in both groups
      while a significant reduction in waist circumference and fat mass was observed
      only with AZP-531. AZP-531 significantly decreased post-prandial glucose levels
      in a baseline glucose dependent fashion. CONCLUSIONS: AZP-531 may constitute a
      new treatment strategy to improve hyperphagia and metabolic issues in patients
      with PWS. These findings support further investigation in longer-term clinical
      trials.

PMID- 29320576
TI  - Targeting DNA repair with PNKP inhibition sensitizes radioresistant prostate
      cancer cells to high LET radiation.
AB  - High linear energy transfer (LET) radiation or heavy ion such as carbon ion
      radiation is used as a method for advanced radiotherapy in the treatment of
      cancer. It has many advantages over the conventional photon based radiotherapy
      using Co-60 gamma or high energy X-rays from a Linear Accelerator. However,
      charged particle therapy is very costly. One way to reduce the cost as well as
      irradiation effects on normal cells is to reduce the dose of radiation by
      enhancing the radiation sensitivity through the use of a radiomodulator. PNKP
      (polynucleotide kinase/phosphatase) is an enzyme which plays important role in
      the non-homologous end joining (NHEJ) DNA repair pathway. It is expected that
      inhibition of PNKP activity may enhance the efficacy of the charged particle
      irradiation in the radioresistant prostate cancer cell line PC-3. To test this
      hypothesis, we investigated cellular radiosensitivity by clonogenic cell survival
      assay in PC-3 cells.12Carbon ion beam of62 MeVenergy (equivalent 5.16
      MeV/nucleon) and with an entrance LET of 287 kev/MUm was used for the present
      study. Apoptotic parameters such as nuclear fragmentation and caspase-3 activity
      were measured by DAPI staining, nuclear ladder assay and colorimetric caspase
      3method. Cell cycle arrest was determined by FACS analysis. Cell death was
      enhanced when carbon ion irradiation is combined with PNKPi (PNKP inhibitor) to
      treat cells as compared to that seen for PNKPi untreated cells. A low
      concentration (10MUM) of PNKPi effectively radiosensitized the PC-3 cells in
      terms of reduction of dose in achieving the same survival fraction. PC-3 cells
      underwent significant apoptosis and cell cycle arrest too was enhanced at G2/M
      phase when carbon ion irradiation was combined with PNKPi treatment. Our findings
      suggest that combined treatment of carbon ion irradiation and PNKP inhibition
      could enhance cellular radiosensitivity in a radioresistant prostate cancer cell
      line PC-3. The synergistic effect of PNKPi and carbon ion irradiation could be
      used as a promising method for carbon-ion therapy in radioresistant cells.

PMID- 29320577
TI  - Genome-wide profiling of the PIWI-interacting RNA-mRNA regulatory networks in
      epithelial ovarian cancers.
AB  - PIWI-interacting (piRNAs), ~23-36 nucleotide-long small non-coding RNAs
      (sncRNAs), earlier believed to be germline-specific, have now been identified in
      somatic cells, including cancer cells. These sncRNAs impact critical biological
      processes by fine-tuning gene expression at post-transcriptional and epigenetic
      levels. The expression of piRNAs in ovarian cancer, the most lethal gynecologic
      cancer is largely uncharted. In this study, we investigated the expression of
      PIWILs by qRT-PCR and western blotting and then identified piRNA transcriptomes
      in tissues of normal ovary and two most prevalent epithelial ovarian cancer
      subtypes, serous and endometrioid by small RNA sequencing. We detected 219, 256
      and 234 piRNAs in normal ovary, endometrioid and serous ovarian cancer samples
      respectively. We observed piRNAs are encoded from various genomic regions, among
      which introns harbor the majority of them. Surprisingly, piRNAs originated from
      different genomic contexts showed the varied level of conservations across
      vertebrates. The functional analysis of predicted targets of differentially
      expressed piRNAs revealed these could modulate key processes and pathways
      involved in ovarian oncogenesis. Our study provides the first comprehensive piRNA
      landscape in these samples and a useful resource for further functional studies
      to decipher new mechanistic views of piRNA-mediated gene regulatory networks
      affecting ovarian oncogenesis. The RNA-seq data is submitted to GEO database
      (GSE83794).

PMID- 29320579
TI  - Emotional modelling and classification of a large-scale collection of scene
      images in a cluster environment.
AB  - The development of network technology and the popularization of image capturing
      devices have led to a rapid increase in the number of digital images available,
      and it is becoming increasingly difficult to identify a desired image from among
      the massive number of possible images. Images usually contain rich semantic
      information, and people usually understand images at a high semantic level.
      Therefore, achieving the ability to use advanced technology to identify the
      emotional semantics contained in images to enable emotional semantic image
      classification remains an urgent issue in various industries. To this end, this
      study proposes an improved OCC emotion model that integrates personality and mood
      factors for emotional modelling to describe the emotional semantic information
      contained in an image. The proposed classification system integrates the k
      Nearest Neighbour (KNN) algorithm with the Support Vector Machine (SVM)
      algorithm. The MapReduce parallel programming model was used to adapt the KNN-SVM
      algorithm for parallel implementation in the Hadoop cluster environment, thereby
      achieving emotional semantic understanding for the classification of a massive
      collection of images. For training and testing, 70,000 scene images were randomly
      selected from the SUN Database. The experimental results indicate that users with
      different personalities show overall consistency in their emotional understanding
      of the same image. For a training sample size of 50,000, the classification
      accuracies for different emotional categories targeted at users with different
      personalities were approximately 95%, and the training time was only 1/5 of that
      required for the corresponding algorithm with a single-node architecture.
      Furthermore, the speedup of the system also showed a linearly increasing
      tendency. Thus, the experiments achieved a good classification effect and can lay
      a foundation for classification in terms of additional types of emotional image
      semantics, thereby demonstrating the practical significance of the proposed
      model.

PMID- 29320578
TI  - The potent effect of mycolactone on lipid membranes.
AB  - Mycolactone is a lipid-like endotoxin synthesized by an environmental human
      pathogen, Mycobacterium ulcerans, the causal agent of Buruli ulcer disease.
      Mycolactone has pleiotropic effects on fundamental cellular processes (cell
      adhesion, cell death and inflammation). Various cellular targets of mycolactone
      have been identified and a literature survey revealed that most of these targets
      are membrane receptors residing in ordered plasma membrane nanodomains, within
      which their functionalities can be modulated. We investigated the capacity of
      mycolactone to interact with membranes, to evaluate its effects on membrane lipid
      organization following its diffusion across the cell membrane. We used Langmuir
      monolayers as a cell membrane model. Experiments were carried out with a lipid
      composition chosen to be as similar as possible to that of the plasma membrane.
      Mycolactone, which has surfactant properties, with an apparent saturation
      concentration of 1 MUM, interacted with the membrane at very low concentrations
      (60 nM). The interaction of mycolactone with the membrane was mediated by the
      presence of cholesterol and, like detergents, mycolactone reshaped the membrane.
      In its monomeric form, this toxin modifies lipid segregation in the monolayer,
      strongly affecting the formation of ordered microdomains. These findings suggest
      that mycolactone disturbs lipid organization in the biological membranes it
      crosses, with potential effects on cell functions and signaling pathways.
      Microdomain remodeling may therefore underlie molecular events, accounting for
      the ability of mycolactone to attack multiple targets and providing new insight
      into a single unifying mechanism underlying the pleiotropic effects of this
      molecule. This membrane remodeling may act in synergy with the other known
      effects of mycolactone on its intracellular targets, potentiating these effects.

PMID- 29320580
TI  - Detection of fast oscillating magnetic fields using dynamic multiple TR imaging
      and Fourier analysis.
AB  - Neuronal oscillations produce oscillating magnetic fields. There have been trials
      to detect neuronal oscillations using MRI, but the detectability in in vivo is
      still in debate. Major obstacles to detecting neuronal oscillations are (i) weak
      amplitudes, (ii) fast oscillations, which are faster than MRI temporal
      resolution, and (iii) random frequencies and on/off intervals. In this study, we
      proposed a new approach for direct detection of weak and fast oscillating
      magnetic fields. The approach consists of (i) dynamic acquisitions using multiple
      times to repeats (TRs) and (ii) an expanded frequency spectral analysis. Gradient
      echo echo-planar imaging was used to test the feasibility of the proposed
      approach with a phantom generating oscillating magnetic fields with various
      frequencies and amplitudes and random on/off intervals. The results showed that
      the proposed approach could precisely detect the weak and fast oscillating
      magnetic fields with random frequencies and on/off intervals. Complex and phase
      spectra showed reliable signals, while no meaningful signals were observed in
      magnitude spectra. A two-TR approach provided an absolute frequency spectrum
      above Nyquist sampling frequency pixel by pixel with no a priori target frequency
      information. The proposed dynamic multiple-TR imaging and Fourier analysis are
      promising for direct detection of neuronal oscillations and potentially
      applicable to any pulse sequences.

PMID- 29320581
TI  - Prevalence of hand osteoarthritis and knee osteoarthritis in Kashin-Beck disease
      endemic areas and non Kashin-Beck disease endemic areas: A status survey.
AB  - Osteoarthritis (OA) is a considerable health problem worldwide, and the
      prevalence of OA varies in different regions. In this study, the prevalence of OA
      in Kashin-Beck disease (KBD) and non-KBD endemic areas was examined,
      respectively. According to monitoring data, 4 types of regions (including none,
      mild, moderate and high KBD endemic areas) in Heilongjiang and Jilin provinces
      were selected. All local residents were eligible for inclusion criteria have
      undergone X-ray images of hands and anteroposterior image of knees. A total of
      1673 cases were collected, 1446 cases were analyzed after removing the KBD
      patients (227). The overall hand OA and knee OA detection rates were 33.3%
      (481/1446) and 56.6% (818/1446), respectively. After being standardized by age,
      the detection rate of hand OA in the KBD endemic areas was significantly higher
      than that in the non-endemic endemic areas. Differently, there was no significant
      difference in the detection rates of knee OA between the KBD endemic areas and
      the non-endemic area. The correlation coefficient between the severity of OA and
      the severity of knee OA was 0.358 and 0.197 in the KBD and non-KBD endemic areas,
      respectively. Where the KBD historical prevalence level was higher, the severity
      of the residents' hand OA was more serious. The detection rates of hand OA and
      knee OA increased with age. The detection rate of knee OA increased with the
      increase in body mass index. The prevalence of hand OA was closely related to the
      pathogenic factors of Kashin-Beck disease, and the prevalence of knee OA had no
      significant correlation with KBD pathogenic factors.

PMID- 29320584
TI  - The Male Aesthetic Patient: Facial Anatomy, Concepts of Attractiveness, and
      Treatment Patterns.
AB  - <p>BACKGROUND: The number of nonsurgical aesthetic procedures performed in men is
      growing rapidly. However, there are limited data on treatment principles and
      goals for the male aesthetic patient.</p> <p>OBJECTIVE: To review the objective
      data available on male aging and aesthetics and to synthesize with expert opinion
      on treatment considerations specific to male patients.</p> <p>METHODS: Expert
      advisors met to discuss anatomical differences in male versus female facial
      anatomy related to aging, facial treatment preferences in aesthetically oriented
      men, and current dosing data for facial injectable treatments in male versus
      female patients.</p> <p>RESULTS: Symmetry, averageness, sexual dimorphism, and
      youthfulness are generally accepted as factors that contribute to the perception
      of attractiveness. There are differences between men and women in facial anatomy,
      concepts of attractiveness in the context of masculinity and femininity, and
      treatment objectives. A communication gap exists for men, as evidenced by the
      lack of information available online or by word of mouth about injectable
      treatments.</p> <p>CONCLUSIONS: Approaches to aesthetic consultation and
      treatment should differ between men and women based on the fundamental
      dissimilarities between the sexes. Educating men about available aesthetic
      treatments and about the safety and side effects associated with each treatment,
      as well as addressing concerns about their treatment results looking natural, are
      key considerations.</p> <p><em>J Drugs Dermatol. 2018;17(1):19-28.</em></p>.

PMID- 29320583
TI  - A Multi-Center, Open-Label, Prospective Study of Cannula Injection of Small
      Particle Hyaluronic Acid Plus Lidocaine (SPHAL) for Lip Augmentation.
AB  - <p>BACKGROUND: The use of blunt-tipped microcannulas for injection of hyaluronic
      acid (HA) filler in the lip and perioral area has gained popularity as they
      provide important safety-related advantages compared to traditional hypodermic
      needles. This study was conducted to assess the safety and effectiveness
      associated with the use of a blunt-tipped microcannula for lip augmentation and
      correction of perioral rhytids using a small-particle, hyaluronic acid gel plus
      lidocaine (SPHAL).</p> <p>METHODS: A multi-center, open-label, prospective, study
      enrolled 60 subjects. Subjects reported injection-related events (IREs) for 2
      weeks posttreatment via diary. Adverse events (AEs) were collected throughout the
      study. Secondary assessments at 4 and 12 weeks posttreatment included treating
      investigator- and subject-reported improvement in lip fullness using the Global
      Aesthetic Improvement Scale (GAIS) and investigator-assessed improvement in lip
      fullness using the Medicis Lip Fullness Scale (MLFS).</p> <p>RESULTS: Sixty
      subjects were enrolled and treated with a mean total volume (ie, both lips and
      optional perioral rhytids) of 2.2 mL. Treatment-emergent adverse events (TEAEs)
      reported and assessed as related to the product and/or injection procedure
      included injection site swelling (13.3%), injection site bruising (6.7%), and
      injection site pain (1.7%). These were typically mild and transient in nature. No
      serious AEs (SAEs) were reported. Following treatment, clinically significant
      improvement using the GAIS and MLFS was demonstrated throughout the study (GAIS
      improvement at week 12 for both lips: investigator-reported, 98.0%; subject
      reported, 84.3%; MLFS improvement at week 12: investigator-reported, 96.1%).</p>
      <p>CONCLUSION: SPHAL was well tolerated and effective following injection with a
      blunt-tipped microcannula. No unanticipated safety concerns were identified in
      the study population.</p> <p><em>J Drugs Dermatol. 2018;17(1):10-16.</em></p>.

PMID- 29320585
TI  - Liposuction of the Neck: Low Incidence of Nerve Injury and Other Complications in
      987 Patients.
AB  - <p>The neck is one of the most common areas treated by liposuction. Neck
      liposuction decreases fat volume, causes skin contraction, and restores a more
      youthful appearance. We present a large case series (n=987) performed by three
      dermatologic surgeons. Five patients developed temporary post-operative marginal
      mandibular dysfunction, one patient had submandibular gland ptosis and one
      patient had arterial bleeding. Seroma, skin necrosis, scarring, and
      hyperpigmentation did not occur following neck liposuction. Neck liposuction
      performed with tumescent local anesthesia is a safe procedure associated with a
      low incidence of nerve injury and other complications.</p> <p><em>J Drugs
      Dermatol. 2018;17(1):30-34.</em></p>.

PMID- 29320582
TI  - Thyroid transcriptome analysis reveals different adaptive responses to cold
      environmental conditions between two chicken breeds.
AB  - Selection for cold tolerance in chickens is important for improving production
      performance and animal welfare. The identification of chicken breeds with higher
      cold tolerance and production performance will help to target candidates for the
      selection. The thyroid gland plays important roles in thermal adaptation, and its
      function is influenced by breed differences and transcriptional plasticity, both
      of which remain largely unknown in the chicken thyroid transcriptome. In this
      study, we subjected Bashang Long-tail (BS) and Rhode Island Red (RIR) chickens to
      either cold or warm environments for 21 weeks and investigated egg production
      performance, body weight changes, serum thyroid hormone concentrations, and
      thyroid gland transcriptome profiles. RIR chickens had higher egg production than
      BS chickens under warm conditions, but BS chickens produced more eggs than RIRs
      under cold conditions. Furthermore, BS chickens showed stable body weight gain
      under cold conditions while RIRs did not. These results suggested that BS breed
      is a preferable candidate for cold-tolerance selection and that the cold
      adaptability of RIRs should be improved in the future. BS chickens had higher
      serum thyroid hormone concentrations than RIRs under both environments. RNA-Seq
      generated 344.3 million paired-end reads from 16 sequencing libraries, and about
      90% of the processed reads were concordantly mapped to the chicken reference
      genome. Differential expression analysis identified 46-1,211 genes in the
      respective comparisons. With regard to breed differences in the thyroid
      transcriptome, BS chickens showed higher cell replication and development, and
      immune response-related activity, while RIR chickens showed higher carbohydrate
      and protein metabolism activity. The cold environment reduced breed differences
      in the thyroid transcriptome compared with the warm environment. Transcriptional
      plasticity analysis revealed different adaptive responses in BS and RIR chickens
      to cope with the cold, and showed higher responsiveness in BS compared with RIR
      chickens, suggesting greater adaptability of the thyroid in BS chickens.
      Moreover, 10,053 differential splicing events were revealed among the groups,
      with RNA splicing and processing, gene expression, transport, and metabolism
      being the main affected biological processes, identifying a valuable alternative
      splicing repertoire for the chicken thyroid. A short isoform of TPO (encoding
      thyroid peroxidase) containing multiple open reading frames was generated in both
      breeds by skipping exons 4 and 5 in the cold environment. These findings provide
      novel clues for future studies of the molecular mechanisms underlying cold
      adaptation and/or acclimation in chickens.

PMID- 29320586
TI  - Safety and Efficacy of a 1550nm/1927nm Dual Wavelength Laser for the Treatment of
      Photodamaged Skin.
AB  - <p>BACKGROUND: Fractional photothermolysis (FP) is a popular treatment option for
      photodamaged skin and addresses shortcomings of ablative skin resurfacing and
      nonablative dermal remodeling. Previous studies have demonstrated that FP using
      the 1550nm wavelength has led to improvement of ultrastructural changes and
      clinical effects associated with photodamaged skin in the deeper dermal
      structures, while treatment with the 1927nm wavelength has shown clinical effects
      in the superficial dermis. Both wavelengths produce precise microscopic treatment
      zones (MTZs) in the skin. The two wavelengths used in combination may optimize
      the delivery of fractional nonablative resurfacing intended for dermal and
      epidermal coagulation of photodamage skin.</p> <p>OBJECTIVES: To evaluate the
      safety and efficacy of a 1550/1927 Laser System (Fraxel Dual, Solta), using both
      1550nm and 1927nm wavelengths in combination for treatment of facial and non
      facial photodamage.</p> <p>METHODS: Prospective, multi-center, post-market study
      in subjects with clinically identifiable photodamage (N=35) (Fitzpatrick skin
      types I-IV). Both 1550nm and 1927nm wavelengths were used at each treatment
      visit. Investigator assessment of the affected area(s) occurred at one week, one
      month and 3 months after a series of up to four treatments. Severity of adverse
      events (AEs) were assessed using a 4-point scale (where 0=none and 3=marked).
      Assessments included erythema, edema, hyperkeratosis, hyper- and hypo
      pigmentation, scarring, itchiness, dryness, and flaking. Severity of photoaging,
      fine and coarse wrinkling, mottled hyperpigmentation, sallowness, and tactile
      roughness at baseline was assessed using the same scale. Investigators and
      subjects assessed overall appearance of photodamage and pigmentation based on a 5
      point quartile improvement scale at all follow-up visits (where 0=no improvement
      and 4=very significant improvement [76%-100%]).</p> <p>RESULTS: There was a
      positive treatment effect at all study visits, with moderate improvement (average
      reduction in severity of 21%-43%) observed 3-months after final treatment.
      Greatest reduction in severity of other benefit areas was at the 3-month follow
      up visit, with a 21% and 30% decrease in severity in fine wrinkling and tactile
      roughness. No AEs or serious AEs were reported. Pain sensation during treatment
      was tolerable. Anticipated moderate erythema (mean score 1.6+/-0.5) and mild
      edema (mean score 0.8+/-0.7) were transient and resolved within 7-10 days.
      Anticipated and transient mild dryness (52% of subjects) and flaking (30%) were
      reported at the 1-week follow-up. There were no incidences of hyperkeratosis,
      scarring, or itchiness.</p> <p>CONCLUSION: Treatments using both wavelengths
      associated with the combined 1550/1927 Laser System were well tolerated with
      limited, transient anticipated side effects and no serious AEs. Clinical efficacy
      in the appearance of photodamage and pigmentation was greatest following a series
      of up to 3 treatments.</p> <p><em>J Drugs Dermatol. 2018;17(1):41-46.</em></p>.

PMID- 29320587
TI  - A Randomized Study to Assess the Efficacy of Skin Rejuvenation Therapy in
      Combination With Neurotoxin and Full Facial Filler Treatments.
AB  - <p>BACKGROUND: Although non-surgical treatment options for facial rejuvenation
      are well-established, the literature remains limited regarding the combined
      effect of topical skin treatment with filler and neurotoxin on patient appearance
      and satisfaction. The objectives of this study were to assess the impact of a
      skin rejuvenation therapy in combination with neurotoxin or hyaluronic acid
      filler injection on skin quality and general aesthetic improvement as well as on
      short-term self-esteem.</p> <p>METHODS: From 2015 to 2017, 20 female patients
      were enrolled in our study and were randomized into two groups. Patients in Group
      A used a basic skin care regimen following hyaluronic acid filler and neurotoxin
      treatment, while those in Group B utilized the Nu-Derm(r) skin care system (Obagi
      Medical Products, Inc) afterwards. Each subject and the principal investigator
      filled out various assessments pre- and post-treatment to evaluate for change in
      skin quality (Fitzpatrick Wrinkle Assessment Scale [FWAS] and Skin Quality
      Assessments [SQA]), aesthetic appearance (Global Aesthetic Improvement Scale
      [GAIS]), patient satisfaction (Subject Satisfaction Assessment [SSA]), and self
      esteem (State Self-Esteem Scale [SSES]).</p> <p>RESULTS: Subjects in both
      treatment groups demonstrated significant improvement in skin quality, as
      illustrated in the change in FWAS and SQA scores, at 12 weeks after initiating
      full facial rejuvenation treatment. However, there were no significant
      differences in FWAS and SQA ratings between the treatment groups. Regarding
      aesthetic appearance, a statistically significant difference in GAIS scores
      between Groups A and B was observed at 6 weeks after treatment only. In
      evaluating for patient satisfaction and self-esteem, there were no significant
      differences in SSA and SSES ratings over time within each treatment group or
      between the treatment groups.</p> <p>CONCLUSIONS: Our study confirms that facial
      rejuvenation therapy involving hyaluronic acid filler and neurotoxin injections
      combined with a topical skin treatment regimen leads to improvement in skin
      quality and aesthetic appearance as well as to patient satisfaction. Additional
      larger studies are needed to better delineate the most ideal combination facial
      rejuvenation therapy for optimizing patient appearance and satisfaction.</p>
      <p><em>J Drugs Dermatol. 2018;17(1):48-54.</em></p>.

PMID- 29320588
TI  - A Guide to Tissue-Engineered Skin Substitutes.
AB  - <p>Wounds that exhibit delayed healing have a tremendous impact on health care
      expenditures and place patients at serious risk for severe complications
      including death. The healing of a chronic wound requires the restoration of
      multiple factors that normally work in concert to repair the damaged skin
      barrier. Skin substitutes have shown great promise for use as adjunctive
      therapies for refractory wounds by providing cells, soluble mediators, and
      extracellular matrix materials needed to stimulate healing. There are a growing
      variety of skin substitutes available on the market with many indications, and
      appropriate selection can impact healing outcomes. Skin substitutes can be
      broadly divided into cellular and acellular devices, yet within these categories,
      each product has its own unique composition and mechanism for promoting healing.
      Here we summarize the characteristics and indications of cellular and acellular
      matrices commonly used in wound care with the most evidence supported by
      randomized control trials and prospective studies. This review aims to provide
      dermatologists and other wound care clinicians with a helpful guide on how to
      approach skin substitutes, from preparing the wound bed for application, to
      making the proper selection for patients' individual wounds.</p> <p><em>J Drugs
      Dermatol. 2018;17(1):57-64.</em></p>.

PMID- 29320590
TI  - Treatment of Decolletage Photoaging With Fractional Microneedling Radiofrequency.
AB  - OBJECTIVES: The objective of this study was to examine the efficacy and safety of
      a novel fractional microneedling radiofrequency device to improve the appearance
      of rhytides and skin laxity of the decolletage. METHODS: Twelve subjects received
      a total of three fractional microneedling radiofrequency treatments with Endymed
      Intensif (EndyMed Ltd., Cesarea, Israel) at least three weeks apart. Primary
      outcome measure was clinical efficacy quantified by a patient survey to assess
      treatment satisfaction as well as a physician Global Aesthetic Improvement Scale
      (GAIS). Photos were taken before every treatment and at a follow-up appointment.
      RESULTS: Assessments by two board-certified dermatologists revealed an overall
      improvement in 67% of patients. Seventy percent of subjects rated their post
      treatment skin laxity and rhytides as improved, while 60% of patients rated their
      skin texture as improved. Eighty percent of subjects were at least slightly
      satisfied with their treatment. Forty percent of subjects would recommend this
      treatment to others. CONCLUSIONS: Subjects in this study demonstrated an overall
      improvement in decolletage appearance in regard to skin tightening, wrinkles, and
      skin texture suggested by overall patient satisfaction (80%) and physician-rated
      GAIS improvement (67%). This study suggests that fractional microneedling
      radiofrequency devices are a safe and efficacious way to improve overall
      decolletage appearance with little down time. <p><em>J Drugs Dermatol.
      2018;17(1):74-76.</em></p>.

PMID- 29320589
TI  - A Multicenter, Double-Blinded, Randomized, Split-Face Study of the Safety and
      Efficacy of a Novel Hyaluronic Acid Gel for the Correction of Nasolabial Folds.
AB  - BACKGROUND: Injectable hyaluronic acid is frequently used to correct volume loss
      in nasolabial folds. OBJECTIVE: To compare the safety and efficacy of a novel
      hyaluronic acid gel to a non-animal stabilized hyaluronic acid (Comparator) gel
      for the correction of nasolabial folds (NLF). METHODS: Qualified subjects had NLF
      with a Wrinkle Severity Rating Scale (WSRS) score of 3 or 4 (moderate or severe).
      NLFs were treated with Test Product on one side of the face and Comparator on the
      other side of the face (facial side randomly assigned). Improvement from baseline
      was evaluated at weeks 1, 2, 4, 12, and 24 weeks. The primary study endpoint was
      the mean change in WSRS score from baseline to week 24. RESULTS: The mean changes
      in WSRS score from baseline were 1.02 +/-0.689 for Test Product and 0.91+/-0.762
      for Comparator. The mean difference in change from baseline in WSRS scoring
      (Comparator minus Test Product) at week 24 was -0.11 (-0.225-0.001, 95%
      confidence interval [CI]). The upper boundary (0.001) of the 95% CI was less than
      the prespecified non-inferiority limit of 0.50, indicating that the Test Product
      was non-inferior to the Comparator. No subject discontinued the study due to
      adverse events. CONCLUSION: The Test Product is safe and non-inferior to the
      Comparator for the correction of nasolabial folds. The Test Product was
      associated with less swelling, pain, and overall severity of treatment-emergent
      adverse events than the Comparator. <p><em>J Drugs Dermatol. 2018;17(1):66
      73.</em></p>.

PMID- 29320591
TI  - The Use of an Over-the-Counter Hand Cream With Sweet Almond Oil for the Treatment
      of Hand Dermatitis.
AB  - Hand dermatitis is estimated to affect greater than 15% of the general
      population. Childhood eczema, frequent hand washing, and occupational exposure to
      chemicals are predisposing factors. Hand dermatitis treatment involves both
      prevention of outbreaks and treatment of active disease. Moisturizers are
      essential to protect the skin from the environment, enhance hydration, and repair
      the skin barrier. They have been shown in large studies to prevent occupational
      related breakouts. Natural oils are commonly used in moisturizers for their
      moisturizing and emollient properties. Sweet almond oil is an oil that contains
      high levels of fatty acids and has been used for centuries to treat skin diseases
      such as eczema and psoriasis. In this study, a moisturizer with 7% sweet almond
      oil and 2% colloidal oatmeal was found to be both safe and effective in treating
      patients with moderate to severe hand dermatitis. <p><em>J Drugs Dermatol.
      2018;17(1):78-82.</em></p>.

PMID- 29320592
TI  - Injectable Non-Animal Stabilized Hyaluronic Acid as a Skin Quality Booster: An
      Expert Panel Consensus.
AB  - Hyaluronic acid (HA) is used extensively in aesthetic medicine thanks to its
      documented role in skin rejuvenation. The specific applications of HA-based
      products are not always fully acknowledged due to a lack of consistent
      recommendations. In this paper, the authors have summarized available published
      data on the range of applications of non-animal stabilized hyaluronic acid
      (NASHA(r)) gel skin boosters (NSBs) in several anatomical areas and types of
      patient, as well as their own recommendations. Overall, the panel agreed that a
      standard initial protocol treatment of up to 3 sessions, followed by a
      maintenance schedule, would allow patients to improve and then preserve skin
      quality over time. Indeed, distinct effects are evident after the first session,
      but a progressive enhancement of skin texture is detectable for up to 12 months
      after repeat treatment at 4 to 6 month intervals. Moreover, the authors agreed
      that the NASHA gel, reaching the dermis, is able to reestablish a greater degree
      of hydration and stimulate collagen that, in turn, restores the volume and
      density of the skin. Thus, a strong consensus was reached that NSB procedures are
      minimally invasive, safe, and effective, and designed to improve skin texture and
      maintain skin quality. <p><em>J Drugs Dermatol. 2018;17(1):83-88.</em></p>.

PMID- 29320593
TI  - Injection Depth in Intradermal Therapy: Update and Correction of Published Data.
AB  - BACKGROUND: This paper sought to compare calculated injection depth data with
      published report claims concerning intradermal therapy and skin rejuvenation of
      the face, hands, neck, and decollete. OBJECTIVE: A mathematical formula was
      employed to assess the injection depth, and data from literature were retrieved
      and compared with the calculated figures to determine whether the claims about
      the injection depth proved correct. METHODS: Based on a study by Della Volpe et
      al., involving 140 skin residues adapted for plastic surgery, we have calculated
      injection depths from published reports on intradermal therapy and skin
      rejuvenation while comparing these figures with the published injection depth
      claims. RESULTS: Most injections were not performed at the claimed depth, with
      over 70% of them carried out in the fat layer, thus, the hypodermis. This is not
      the recommended depth for a refined injection technique in the intradermal
      therapy field. CONCLUSION: Whilst examining our study results, two different
      possibilities come to mind. We must either: 1) review and correct the existing
      histological classification; and/or 2) better learn to correctly inject in the
      superficial-dermis, mid-dermis, and deep-dermis. In other words, a perfect
      control over the needle penetration angle and implanted part appears urgently
      required. <p><em>J Drugs Dermatol. 2018;17(1):89-96.</em></p>.

PMID- 29320594
TI  - Pivotal Trial of the Efficacy and Safety of Oxymetazoline Cream 1.0% for the
      Treatment of Persistent Facial Erythema Associated With Rosacea: Findings from
      the First REVEAL Trial.
AB  - An unmet need exists for a safe, tolerable, effective treatment for moderate to
      severe persistent facial erythema in patients with rosacea. This pivotal phase 3,
      multicenter, double-blind study evaluated the efficacy and safety of topical
      oxymetazoline in patients with facial erythema associated with moderate to severe
      rosacea. Patients were randomly assigned to treatment with oxymetazoline
      hydrochloride cream 1.0% or vehicle applied once daily for 29 days, and were
      followed for 28 days posttreatment. The primary efficacy outcome was having at
      least a 2-grade decrease from baseline on both the Clinician Erythema Assessment
      (CEA) and the Subject Self-Assessment for rosacea facial redness (SSA) scales
      (composite success) at 3, 6, 9, and 12 hours postdose on day 29. Safety
      assessments included treatment-emergent adverse events (TEAEs) and posttreatment
      worsening of erythema (composite CEA/SSA increase of 1-grade severity from
      baseline; rebound effect). A total of 440 patients (mean age, 49.5 years; 78.9%
      females) were randomized (oxymetazoline, n=222; vehicle, n=218); most had
      moderate erythema. On day 29, significantly greater proportions of oxymetazoline
      recipients achieved the primary efficacy outcome at each time point (P less than
      0.02) and overall (P less than 0.001) compared with vehicle recipients. The
      incidence of discontinuation due to TEAEs was low in both groups (oxymetazoline
      group, 1.8%; vehicle group, 0.5%). The most common TEAEs reported during the
      entire study period were application-site dermatitis, application-site erythema,
      and headache in the oxymetazoline group (1.4% each), and headache (0.9%) in the
      vehicle group. Following cessation of treatment, low proportions of patients
      experienced rebound effect (oxymetazoline group, 2.2%; vehicle group, 1.1%).
      Oxymetazoline applied to the face once daily for 29 days was effective, safe, and
      well tolerated in patients with moderate to severe persistent facial erythema of
      rosacea. <p><em>J Drugs Dermatol. 2018;17(1):97-105.</em></p>.

PMID- 29320595
TI  - Safety and Efficacy of a Non-Invasive 1060 nm Diode Laser for Fat Reduction of
      the Abdomen.
AB  - BACKGROUND: Changes in temperature are known to produce apoptosis in adipocytes.
      This study examines the use of a non-invasive treatment that applies 1060 nm
      laser energy transcutaneously to hyperthermically induce disruption of fat cells
      in the abdomen. METHODS: Thirty-five subjects received application of 1060 nm
      laser on the abdomen for fat reduction. Ultrasound images and high-resolution two
      dimensional photography were recorded at baseline, 6 weeks, and 12 weeks post
      treatment. Subjects maintained a stable diet and exercise routine throughout the
      course of the study. Weight was recorded at baseline and each follow-up visit.
      Three board certified dermatologists were trained as blinded evaluators and
      tasked with identifying before and after photographs from randomized, paired
      baseline, and 12-week photographs. Ultrasound images were used to measure the fat
      thickness change from baseline at 6 and 12 weeks. Level of patient satisfaction
      was graded at 12 weeks using a 6 point Likert scale. REULTS: 23% of subjects were
      Fitzpatrick IV-VI. Blinded evaluators correctly identified the post-treatment
      photograph 95% of the time (88%, 97%, and 100%). Mean reduction in fat layer
      thickness from baseline was statistically significant (P less than 0.001) at both
      6 weeks (1.5 +/-1.23 mm) and 12 weeks (2.65 +/-1.41 mm). Mean weight change was
      +0.1 lb. Side effects were mild to moderate including edema, tenderness, and
      induration mostly resolving within 1-3 weeks post treatment. No serious adverse
      events were reported. CONCLUSION: 1060 nm based laser treatment can consistently
      reduce the fat contour in the abdomen with an excellent safety profile in all
      skin types. The study met all three of its prospectively defined endpoints of
      success. <p><em>J Drugs Dermatol. 2018;17(1):106-112.</em></p> <p>THIS ARTICLE
      HAD BEEN MADE AVAILABLE FREE OF CHARGE.</p> <p>PLEASE SCROLL DOWN TO ACCESS THE
      FULL TEXT OF THIS ARTICLE WITHOUT LOGGING IN.</p> <p>NO PURCHASE NECESSARY.</p>
      <p>PLEASE CONTACT THE PUBLISHER WITH ANY QUESTIONS.</p>.

PMID- 29320596
TI  - Double Blind, Placebo Controlled Evaluation of a Novel Skin Lightening Agent.
AB  - Melasma remains a troubling problem for physicans and patients alike. It is a
      chronic irregular, symmetric hyperpigmentation seen most often in women. In this
      study, a unique combination of ingredients with non-irritating properties was
      tested for treatment of melasma. In a double blind, placebo controlled, split
      face trial, 17 patients with melasma were treated on one half of the face, left
      or right, while the other received placebo control. All patients used sunscreen
      on both sides. Measurement with a colorimeter (Mexameter) was taken at baseline
      and after 8 weeks of daily use. The active side showed an objective decrease in
      hyperpigmentation of 14.60% while the control side showed a decrease of 9.82%. We
      conclude the product provides a non-irritating effective therapy for melasma.
      <p><em>J Drugs Dermatol. 2018;17(1):113-115.</em></p>.

PMID- 29320597
TI  - Realistic Sunscreen Durability: A Randomized, Double-blinded, Controlled Clinical
      Study.
AB  - BACKGROUND: Studies show that sunscreen under real-life conditions is often not
      reapplied and/or applied insufficiently. This study investigated the durability
      of 2 current sunscreens with different SPF protection over an 8-hour period under
      simulated real-life conditions. METHODS: Participants (n=24) were randomized into
      two study groups utilizing either 2 mg/cm2 (FDA testing concentration) or 1
      mg/cm2 (real-life application levels) of sunscreen. Two current SPF 15 and 70
      sunscreens were applied to test spots on each participant's back. SPF values were
      obtained at baseline, 3.5, and 8 hours after initial application, during which
      subjects completed 30 minutes of moderate exercise followed by 80 minutes of
      water exposure. RESULTS: Participants in both dose study groups revealed only a
      15-40% overall decrease in their SPF protection 8 hours after application. The
      study group that received half the FDA test concentration of sunscreen achieved
      approximately half or less the labeled SPF. At 8 hours, the test sites that
      received SPF 70 maintained an average SPF greater than 64 (2 mg/cm2 application)
      and 26 (1 mg/cm2 application). Similarly, the SPF 15 product test sites revealed
      an in vivo protection of 13 (2 mg/cm2) and 7 (1 mg/cm2). CONCLUSION: This study
      demonstrates that current sunscreens may be durable on skin even following
      significant exercise and water exposure, suggesting that reapplication intervals
      may be longer than currently recommended. In addition, the higher SPF sunscreen
      maintained a skin cancer-protective level of SPF following extended use. <p><em>J
      Drugs Dermatol. 2018;17(1):116-117.</em></p>.

PMID- 29320598
TI  - Eruptive Sebaceous Hyperplasia: A Rare Consequence of Systemic Corticosteroids.
AB  - BACKGROUND: Eruptive sebaceous hyperplasia is a rare and poorly understood
      consequence of immunosuppression, most commonly with cyclosporine, following
      organ transplantation. To date, there have been no reports documenting eruptive
      sebaceous hyperplasia associated with the utilization of immunosuppression
      outside of this clinical scenario. OBSERVATION: A 43-year-old Caucasian male with
      a significant history for Crohn's disease presented with the sudden appearance of
      multiple asymptomatic growths now present for several weeks. They were first
      noted two weeks following the initiation of a slow prednisone taper prescribed
      for a recent exacerbation of Crohn's disease. Skin examination revealed multiple
      1-3mm, soft, skin colored to yellowish, dome-shaped, umbilicated papules on the
      forehead and the bilateral lateral/malar cheeks, clinically suggestive and
      confirmed histologically as sebaceous hyperplasia. CONCLUSION: To our knowledge,
      this is the first reported case of eruptive sebaceous hyperplasia secondary to
      the use of prednisone in a patient with Crohn's disease. This case brings
      awareness to the unique side effect of prednisone induced sebaceous hyperplasia,
      and demonstrates the importance of educating patients with Crohn's disease of
      this potential side effect when prescribing this medication. <p><em>J Drugs
      Dermatol. 2018;17(1):118-120.</em></p>.

PMID- 29320599
TI  - Asymmetric Catalytic Preparation of Polysubstituted Cyclopropanol and
      Cyclopropylamine Derivatives.
AB  - The catalytic asymmetric carbometalation of cyclopropenes followed by either an
      electrophilic oxidation or amination reaction provides a unique approach to the
      formation of diastereomerically pure and enantiomerically enriched cyclopropanol
      and cyclopropylamine derivatives, respectively.

PMID- 29320600
TI  - Providing physicians with feedback on medication adherence for people with
      chronic diseases taking long-term medication.
AB  - BACKGROUND: Poor medication adherence decreases treatment efficacy and worsens
      clinical outcomes, but average rates of adherence to long-term pharmacological
      treatments for chronic illnesses are only about 50%. Interventions for improving
      medication adherence largely focus on patients rather than on physicians;
      however, the strategies shown to be effective are complex and difficult to
      implement in clinical practice. There is a need for new care models addressing
      the problem of medication adherence, integrating this problem into the patient
      care process. Physicians tend to overestimate how well patients take their
      medication as prescribed. This can lead to missed opportunities to change
      medications, solve adverse effects, or propose the use of reminders in order to
      improve patients' adherence. Thus, providing physicians with feedback on
      medication adherence has the potential to prompt changes that improve their
      patients' adherence to prescribed medications. OBJECTIVES: To assess the effects
      of providing physicians with feedback about their patients' medication adherence
      for improving adherence. We also assessed the effects of the intervention on
      patient outcomes, health resource use, and processes of care. SEARCH METHODS: We
      conducted a systematic search of the Cochrane Central Register of Controlled
      Trials (CENTRAL), MEDLINE, and Embase, all from database inception to December
      2016 and without any language restriction. We also searched ISI Web of Science,
      two trials registers, and grey literature. SELECTION CRITERIA: We included
      randomised trials, controlled before-after studies, and interrupted time series
      studies that compared the effects of providing feedback to physicians about their
      patients' adherence to prescribed long-term medications for chronic diseases
      versus usual care. We included published or unpublished studies in any language.
      Participants included any physician and any patient prescribed with long-term
      medication for chronic disease. We included interventions providing the
      prescribing physician with information about patient adherence to medication.
      Only studies in which feedback to the physician was the sole intervention or the
      essential component of a multifaceted intervention were eligible. In the
      comparison groups, the physicians should not have had access to information about
      their patients' adherence to medication. We considered the following outcomes:
      medication adherence, patient outcomes, health resource use, processes of care,
      and adverse events. DATA COLLECTION AND ANALYSIS: Two independent review authors
      extracted and analysed all data using standard methodological procedures expected
      by Cochrane and the Effective Practice and Organisation of Care group. Due to
      heterogeneity in study methodology, comparison groups, intervention settings, and
      measurements of outcomes, we did not carry out meta-analysis. We describe the
      impact of interventions on outcomes in tabular form and make a qualitative
      assessment of the effects of studies. MAIN RESULTS: We included nine studies
      (23,255 patient participants): eight randomised trials and one interrupted time
      series analysis. The studies took place in primary care and other outpatient
      settings in the USA and Canada. Seven interventions involved the systematic
      provision of feedback to physicians concerning all their patients' adherence to
      medication, and two interventions involved issuing an alert for non-adherent
      patients only. Seven studies used pharmacy refill data to assess medication
      adherence, and two used an electronic device or self-reporting. The definition of
      adherence differed across studies, making comparisons difficult. Eight studies
      were at high risk of bias, and one study was at unclear risk of bias. The most
      frequent source of bias was lack of protection against contamination.Providing
      physicians with feedback may lead to little or no difference in medication
      adherence (seven studies, 22,924 patients), patient outcomes (two studies, 1292
      patients), or health resource use (two studies, 4181 patients). Providing
      physicians with feedback on medication adherence may improve processes of care
      (e.g. more medication changes, dialogue with patient, management of uncontrolled
      hypertension) compared to usual care (four studies, 2780 patients). None of the
      studies reported an adverse event due to the intervention. The certainty of
      evidence was low for all outcomes, mainly due to high risk of bias, high
      heterogeneity across studies, and indirectness of evidence. AUTHORS' CONCLUSIONS:
      Across nine studies, we observed little or no evidence that provision of feedback
      to physicians regarding their patients adherence to prescribed medication
      improved medication adherence, patient outcomes, or health resource use. Feedback
      about medication adherence may improve processes of care, but due to the small
      number of studies assessing this outcome and high risk of bias, we cannot draw
      firm conclusions on the effect of feedback on this outcome. Future research
      should use a clear, standardised definition of medication adherence and cluster
      randomisation to avoid the risk of contamination.

PMID- 29320601
TI  - Surfactant-Enhanced Electroosmotic Flushing in a Trichlorobenzene Contaminated
      Clayey Soil.
AB  - Remediation of the sites contaminated with organic contaminants, such as
      chlorobenzenes, remains a challenging issue. Electroosmotic flushing can be a
      promising approach which is based on mechanism of electrokinetic remediation for
      removal of organic contaminants from fluids in low-permeability soil. To select
      an optimum surfactant that can effectively enhance electroosmotic flushing, three
      common surfactants, Triton X-100 (EK2), Tween 80 (EK3), and a mixture of sodium
      dodecyl sulfate and Triton X-100 (EK4) buffered with Na2 HPO4 /NaH2 PO4 solution,
      were tested. The efficiency of each kind of surfactant was evaluated using a
      three-dimensional box filled with a clayey soil spiked with 1,2,4
      trichlorobenzene, and compared with a test (EK1) without surfactant. The results
      demonstrated that the buffer solutions efficiently neutralized H+ and OH-
      produced by electrolysis. EK3 with Tween 80 added in the flushing solution
      reached the highest electroosmotic permeability of 10-4  cm2 /v/s and achieved a
      notably high cumulative electroosmotic flow (EOF) of 5067 mL within 6 d, which
      was 6.3, 3.4, and 4.2 times higher than that in EK1, EK2, and EK4, respectively.
      There were 420 mL more cumulative EOF obtained after 50 h of electrical
      application in EK4 than in EK2. The introduction of nonreactive ions can increase
      the current, thereby benefiting the EOF. Both the higher pH caused by the buffer
      and the application of nonionic surfactants can make the zeta potential more
      negative, thereby increasing the EOF. Tween 80 can be recommended as the best
      flushing solution for removing organic contaminants from sites when
      electrokinetic remediation is applied.

PMID- 29320602
TI  - When metformin is not enough: Pros and cons of SGLT2 and DPP-4 inhibitors as a
      second line therapy.
AB  - The newer oral therapies for type 2 diabetes mellitus, dipeptidyl peptidase-4
      (DPP-4) inhibitors and sodium glucose cotransporter 2 (SGLT2) inhibitors, have
      advantages over older agents. Dipeptidyl peptidase-4 inhibitors are weight
      neutral and have few adverse effects. Sodium glucose cotransporter 2 inhibitors
      have additional benefits: weight loss, blood pressure reduction, cardiovascular
      risk reduction, and renoprotective effects. Sodium glucose cotransporter 2
      inhibitors have increased risk of urogenital infections and possible risk of
      "euglycaemic" diabetic ketoacidosis. It is important to balance the benefits over
      the older-oral therapies as these agents are more expensive; yet some analyses
      suggest that they are within the limits of what is considered cost-effective in
      health care. We discuss the relative merits and drawbacks of these 2 classes and
      consider their roles in the treatment of type 2 diabetes mellitus. We suggest a
      number of patient profiles where early use of these agents could be used. We
      favour the use of SGLT2 inhibitors over DPP-4 inhibitors as add on therapy to
      metformin when glycaemic targets have not been achieved given their similar
      glycaemic efficacy and the additional benefits of SGLT2 inhibitors. We
      particularly favour SGLT2 inhibitors in those where additional weight loss and
      blood pressure reductions are desired, and in patients with heart failure or
      cardiovascular disease. Care should be taken to warn patients about genital
      fungal infections and to avoid use in people with risk factors for SGLT2
      associated ketoacidosis. We favour DPP-4 inhibitors in those where side effects
      of other agents are of concern, the frail elderly population, and those with
      renal disease precluding SGTL2 inhibitor use.

PMID- 29320603
TI  - Drug management for acute tonic-clonic convulsions including convulsive status
      epilepticus in children.
AB  - BACKGROUND: Tonic-clonic convulsions and convulsive status epilepticus (currently
      defined as a tonic-clonic convulsion lasting at least 30 minutes) are medical
      emergencies and require urgent and appropriate anticonvulsant treatment.
      International consensus is that an anticonvulsant drug should be administered for
      any tonic-clonic convulsion that has been continuing for at least five minutes.
      Benzodiazepines (diazepam, lorazepam, midazolam) are traditionally regarded as
      first-line drugs and phenobarbital, phenytoin and paraldehyde as second-line
      drugs. This is an update of a Cochrane Review first published in 2002 and updated
      in 2008. OBJECTIVES: To evaluate the effectiveness and safety of anticonvulsant
      drugs used to treat any acute tonic-clonic convulsion of any duration, including
      established convulsive (tonic-clonic) status epilepticus in children who present
      to a hospital or emergency medical department. SEARCH METHODS: For the latest
      update we searched the Cochrane Epilepsy Group's Specialised Register (23 May
      2017), the Cochrane Central Register of Controlled Trials (CENTRAL) via the
      Cochrane Register of Studies Online (CRSO, 23 May 2017), MEDLINE (Ovid, 1946 to
      23 May 2017), ClinicalTrials.gov (23 May 2017), and the WHO International
      Clinical Trials Registry Platform (ICTRP, 23 May 2017). SELECTION CRITERIA:
      Randomised and quasi-randomised trials comparing any anticonvulsant drugs used
      for the treatment of an acute tonic-clonic convulsion including convulsive status
      epilepticus in children. DATA COLLECTION AND ANALYSIS: Two review authors
      independently assessed trials for inclusion and extracted data. We contacted
      study authors for additional information. MAIN RESULTS: The review includes 18
      randomised trials involving 2199 participants, and a range of drug treatment
      options, doses and routes of administration (rectal, buccal, nasal, intramuscular
      and intravenous). The studies vary by design, setting and population, both in
      terms of their ages and also in their clinical situation. We have made many
      comparisons of drugs and of routes of administration of drugs in this review; our
      key findings are as follows:(1) This review provides only low- to very low
      quality evidence comparing buccal midazolam with rectal diazepam for the
      treatment of acute tonic-clonic convulsions (risk ratio (RR) for seizure
      cessation 1.25, 95% confidence interval (CI) 1.13 to 1.38; 4 trials; 690
      children). However, there is uncertainty about the effect and therefore
      insufficient evidence to support its use. There were no included studies which
      compare intranasal and buccal midazolam.(2) Buccal and intranasal anticonvulsants
      were shown to lead to similar rates of seizure cessation as intravenous
      anticonvulsants, e.g. intranasal lorazepam appears to be as effective as
      intravenous lorazepam (RR 0.96, 95% CI 0.82 to 1.13; 1 trial; 141 children; high
      quality evidence) and intranasal midazolam was equivalent to intravenous diazepam
      (RR 0.98, 95% CI 0.91 to 1.06; 2 trials; 122 children; moderate-quality
      evidence).(3) Intramuscular midazolam also showed a similar rate of seizure
      cessation to intravenous diazepam (RR 0.97, 95% CI 0.87 to 1.09; 2 trials; 105
      children; low-quality evidence).(4) For intravenous routes of administration,
      lorazepam appears to be as effective as diazepam in stopping acute tonic clonic
      convulsions: RR 1.04, 95% CI 0.94 to 1.16; 3 trials; 414 children; low-quality
      evidence. Furthermore, we found no statistically significant or clinically
      important differences between intravenous midazolam and diazepam (RR for seizure
      cessation 1.08, 95% CI 0.97 to 1.21; 1 trial; 80 children; moderate-quality
      evidence) or intravenous midazolam and lorazepam (RR for seizure cessation 0.98,
      95% CI 0.91 to 1.04; 1 trial; 80 children; moderate-quality evidence). In
      general, intravenously-administered anticonvulsants led to more rapid seizure
      cessation but this was usually compromised by the time taken to establish
      intravenous access.(5) There is limited evidence from a single trial to suggest
      that intranasal lorazepam may be more effective than intramuscular paraldehyde in
      stopping acute tonic-clonic convulsions (RR 1.22, 95% CI 0.99 to 1.52; 160
      children; moderate-quality evidence).(6) Adverse side effects were observed and
      reported very infrequently in the included studies. Respiratory depression was
      the most common and most clinically relevant side effect and, where reported, the
      frequency of this adverse event was observed in 0% to up to 18% of children. None
      of the studies individually demonstrated any difference in the rates of
      respiratory depression between the different anticonvulsants or their different
      routes of administration; but when pooled, three studies (439 children) provided
      moderate-quality evidence that lorazepam was significantly associated with fewer
      occurrences of respiratory depression than diazepam (RR 0.72, 95% CI 0.55 to
      0.93).Much of the evidence provided in this review is of mostly moderate to high
      quality. However, the quality of the evidence provided for some important
      outcomes is low to very low, particularly for comparisons of non-intravenous
      routes of drug administration. Low- to very low-quality evidence was provided
      where limited data and imprecise results were available for analysis,
      methodological inadequacies were present in some studies which may have
      introduced bias into the results, study settings were not applicable to wider
      clinical practice, and where inconsistency was present in some pooled analyses.
      AUTHORS' CONCLUSIONS: We have not identified any new high-quality evidence on the
      efficacy or safety of an anticonvulsant in stopping an acute tonic-clonic
      convulsion that would inform clinical practice. There appears to be a very low
      risk of adverse events, specifically respiratory depression. Intravenous
      lorazepam and diazepam appear to be associated with similar rates of seizure
      cessation and respiratory depression. Although intravenous lorazepam and
      intravenous diazepam lead to more rapid seizure cessation, the time taken to
      obtain intravenous access may undermine this effect. In the absence of
      intravenous access, buccal midazolam or rectal diazepam are therefore acceptable
      first-line anticonvulsants for the treatment of an acute tonic-clonic convulsion
      that has lasted at least five minutes. There is no evidence provided by this
      review to support the use of intranasal midazolam or lorazepam as alternatives to
      buccal midazolam or rectal diazepam.

PMID- 29320604
TI  - Reconstruction of molecular network evolution from cross-sectional omics data.
AB  - Cross-sectional studies may shed light on the evolution of a disease like cancer
      through the comparison of patient traits among disease stages. This problem is
      especially challenging when a gene-gene interaction network needs to be
      reconstructed from omics data, and, in addition, the patients of each stage need
      not form a homogeneous group. Here, the problem is operationalized as the
      estimation of stage-wise mixtures of Gaussian graphical models (GGMs) from high
      dimensional data. These mixtures are fitted by a (fused) ridge penalized EM
      algorithm. The fused ridge penalty shrinks GGMs of contiguous stages. The (fused)
      ridge penalty parameters are chosen through cross-validation. The proposed
      estimation procedures are shown to be consistent and their performance in other
      respects is studied in simulation. The down-stream exploitation of the fitted
      GGMs is outlined. In a data illustration the methodology is employed to identify
      gene-gene interaction network changes in the transition from normal to cancer
      prostate tissue.

PMID- 29320605
TI  - Activation of seminal root primordia during wheat domestication reveals
      underlying mechanisms of plant resilience.
AB  - Seminal roots constitute the initial wheat root system and provide the main route
      for water absorption during early stages of development. Seminal root number
      (SRN) varies among species. However, the mechanisms through which SRN is
      controlled and in turn contribute to environmental adaptation are poorly
      understood. Here, we show that SRN increased upon wheat domestication from 3 to 5
      due to the activation of 2 root primordia that are suppressed in wild wheat, a
      trait controlled by loci expressed in the germinating embryo. Suppression of root
      primordia did not limit water uptake, indicating that 3 seminal roots is adequate
      to maintain growth during seedling development. The persistence of roots at their
      primordial state promoted seedling recovery from water stress through
      reactivation of suppressed primordia upon rehydration. Our findings suggest that
      under well-watered conditions, SRN is not a limiting factor, and excessive number
      of roots may be costly and maladaptive. Following water stress, lack of
      substantial root system suppresses growth and rapid recovery of the root system
      is essential for seedling recovery. This study underscores SRN as key adaptive
      trait that was reshaped upon domestication. The maintenance of roots at their
      primordial state during seedling development may be regarded as seedling
      protective mechanism against water stress.

PMID- 29320606
TI  - Splitting Water by Electrochemistry and Artificial Photosynthesis: Excellent
      Science but a Nightmare of Translation?
AB  - Water splitting to its elements, either by electrochemistry or by solar light, is
      among the most covered areas in nanostructured functional materials. This
      personal account article analyzes potential downstream translation problems and
      reviews alternative chemistries with a potential higher return. Liberation of
      oxygen for accepting the holes is a kinetically demanding half reaction afflicted
      with kinetic hindrances and high overpotentials, while at the same time no
      marketable value is created (atmospheric oxygen is free to use). In spite of
      exciting science created, application in real industrial set-ups is currently
      impossible, and possible funding promises to contribute to a sustainable society
      become a debt difficult to return. We discuss possible alternative targets of
      (photo)electrochemistry as entry points where chemical value products and
      technical oxidants are created, with partially greater ease, lower losses, and
      higher benefits.

PMID- 29320608
TI  - Corrigenda.

PMID- 29320609
TI  - British Small Animal Veterinary Association annual general meeting.

PMID- 29320607
TI  - Functional analysis of the seven in absentia ubiquitin ligase family in tomato.
AB  - Seven in absentia (SINA) protein is one subgroup of ubiquitin ligases possessing
      an N-terminal cysteine-rich really interesting new gene (RING) domain, two zinc
      finger motifs, and a C-terminal domain responsible for substrate-binding and
      dimerization. In tomato (Solanum lycopersicum), the SINA gene family has six
      members, and we characterize in this study all tomato SINA (SlSINA) genes and the
      gene products. Our results show that SlSINA genes are differentially regulated in
      leaf, bud, stem, flower, and root. All SlSINA proteins possess RING-dependent E3
      ubiquitin ligase activity, exhibiting similar specificity towards the E2
      ubiquitin-conjugating enzyme. SlSINA1/3/4/5/6 are localized in both cytoplasm and
      nucleus, whereas SlSINA2 is exclusively localized in the nucleus. Moreover, all
      SlSINAs can interact with each other for homo- or hetero-dimerization. The
      functionality of SlSINA proteins has been investigated. SlSINA4 plays a positive
      role in defense signalling, as manifested by elicitation of E3-dependent
      hypersensitive response-like cell death; the other SlSINAs are negative regulator
      and capable to suppress hypersensitive response cell death. Transgenic tomato
      plants overexpressing SlSINA2 exhibit pale-green leaf phenotype, suggesting
      SlSINA2 regulates chlorophyll level in plant cells, whereas transgenic tomato
      plants overexpressing SlSINA5 have altered floral structure with exserted stigma,
      implicating SlSINA5 plays a role in flower development.

PMID- 29320610
TI  - Fabry-Perot Oscillation and Room Temperature Lasing in Perovskite Cube-Corner
      Pyramid Cavities.
AB  - Recently, organometal halide perovskite-based optoelectronics, particularly
      lasers, have attracted intensive attentions because of its outstanding spectral
      coherence, low threshold, and wideband tunability. In this work, high-quality CH3
      NH3 PbBr3 single crystals with a unique shape of cube-corner pyramids are
      synthesized on mica substrates using chemical vapor deposition method. These
      micropyramids naturally form cube-corner cavities, which are eminent candidates
      for small-sized resonators and retroreflectors. The as-grown perovskites show
      strong emission ~530 nm in the vertical direction at room temperature. A special
      Fabry-Perot (F-P) mode is employed to interpret the light confinement in the
      cavity. Lasing from the perovskite pyramids is observed from 80 to 200 K, with
      threshold ranging from ~92 uJ cm-2 to 2.2 mJ cm-2 , yielding a characteristic
      temperature of T0 = 35 K. By coating a thin layer of Ag film, the threshold is
      reduced from ~92 to 26 uJ cm-2 , which is accompanied by room temperature lasing
      with a threshold of ~75 uJ cm-2 . This work advocates the prospect of shape
      engineered perovskite crystals toward developing micro-sized optoelectronic
      devices and potentially investigating light-matter coupling in quantum optics.

PMID- 29320611
TI  - Designing Novel Nonsymmetric Ag/AgI Nanoplates for Superior Photocatalytic
      Activity.
AB  - Precisely engineering the decoration of metal nanoparticles on the special
      surface of semiconductor represents a promising strategy to design efficient
      metal-semiconductor heterostructured photocatalysts. This study demonstrates a
      versatile soft-template method to fabricate a novel nonsymmetrical
      heterostructured Ag/AgI nanoplate, in which only one side surface of the
      nanoplate is covered with uniform 2D Ag nanoweb. Compared with symmetrical
      heterostructure, the nonsymmetrical heterostructure may further facilitate the
      separation of photogenerated electron-hole pairs and shows a greatly enhanced
      photocatalytic activity. This study may open up a new way to improve the
      photocatalytic property by synthesizing nonsymmetrical metal-semiconductor
      composites.

PMID- 29320612
TI  - Precise Synthesis of Well-Defined Inorganic-Organic Hybrid Particles.
AB  - Synthesis of hybrid particles toward precisely designed hierarchical
      nanoarchitectures is summarized. In order to satisfy the demands for a variety of
      materials' performances, the selection of materials, composition and synthesis is
      carefully done. Flow reactors are one of the useful synthetic means to prepare
      hybrid materials, especially those with hierarchically and precisely designed
      multi-components hybrid particles, owing to the efficient mixing and heat
      exchange in the reactor as well as its connectable (both parallel and sequential)
      feature. In this review article, after the summary of the preparation of hybrids
      based on oxides and organics through conventional batch reactors, the application
      of flow reactors to the preparation of various hybrid particles is introduced to
      highlight the present status and future possibility of the flow reactor
      synthesis.

PMID- 29320613
TI  - Halloysite Nanotubes for Cleaning, Consolidation and Protection.
AB  - Herein, we report our recent research concerning the development of halloysite
      based protocols for cleaning, consolidation and protection purposes. Surface
      modification of halloysite cavity by anionic surfactants was explored to
      fabricate inorganic micelles able to solubilize hydrophobic contaminants. Hybrid
      dispersions based on halloysite and ecocompatible polymers were tested as
      consolidants for paper and waterlogged archaeological woods. Encapsulation of
      deacidifying and flame retardant agents within the halloysite lumen was conducted
      with aim to obtain nanofiller with a long-term protection ability. The results
      prove the suitability and versatility of halloysite nanotubes, which are
      perspective inorganic nanoparticles within materials science, remedation and
      conservation of cultural heritage fields.

PMID- 29320614
TI  - Deep Tumor Penetrating Bioparticulates Inspired Burst Intracellular Drug Release
      for Precision Chemo-Phototherapy.
AB  - The relevance of personalized medicine has inspired research for individually
      concerted diagnosis and therapy. Numerous efforts are devoted to designing drug
      particulates with capabilities of tumor penetrating and subcellular trafficking
      to concurrently discharge theranostics in response to multistimulations. In this
      study, a bioinspired particulate, formulated with whole components of native high
      density lipoproteins (HDLs) and decorated with the tumor-penetrating peptide
      iRGD, is proposed to promote tumor penetration of HDLs (pHDLs) together with
      payloads. Specifically, paclitaxel (PTX), and the NIR fluorescent probe
      indocyanine green (ICG) are integrated into pHDLs (pHDL/PTX-ICG) for synergetic
      chemo-phototherapy. Inspired by lipoproteins, pHDLs are not only restored from
      naturally occurring materials but also possessed artificially endowed functions,
      leading to an enhanced cellular uptake, higher accumulation, and deep penetration
      into tumors without causing appreciable adverse effects, compared to
      reconstituted HDLs or lipid-based nanoparticles. After intravenous
      administration, pHDL/PTX-ICG performs a burst of intracellular drug release and
      imaging-guided precision chemo-phototherapy upon NIR irradiation that completely
      eradicates xenograft tumors. Neither recurrence nor significant toxicity is
      observed due to maneuvered regional photodynamic and photothermal therapy. Taken
      together, pHDL/PTX-ICG is proven to be a promising platform to achieve deep tumor
      penetration and imaging-guided chemo-phototherapy.

PMID- 29320615
TI  - An intervertebral disc whole organ culture system to investigate proinflammatory
      and degenerative disc disease condition.
AB  - The aim of this study was to compare the effect of different disease initiators
      of degenerative disc disease (DDD) within an intervertebral disc (IVD) organ
      culture system and to understand the interplay between inflammation and
      degeneration in the early stage of DDD. Bovine caudal IVDs were cultured within a
      bioreactor for up to 11 days. Control group was cultured under physiological
      loading (0.02-0.2 MPa; 0.2 Hz; 2 hr/day) and high glucose (4.5 g/L) medium.
      Detrimental loading (0.32-0.5 MPa, 5 Hz; 2 hr/day) and low glucose (2 g/L) medium
      were applied to mimic the condition of abnormal mechanical stress and limited
      nutrition supply. Tumour necrosis factor alpha (TNF-alpha) was injected into the
      nucleus pulposus (100 ng per IVD) as a proinflammatory trigger. TNF-alpha
      combined with detrimental loading and low glucose medium up-regulated interleukin
      1beta (IL-1beta), IL-6, and IL-8 gene expression in disc tissue, nitric oxide,
      and IL-8 release from IVD, which indicate a proinflammatory effect. The combined
      initiators up-regulated matrix metalloproteinase 1 gene expression, down
      regulated gene expression of Type I collagen in annulus fibrosus and Type II
      collagen in nucleus pulposus, and reduced the cell viability. Furthermore, the
      combined initiators induced a degradative effect, as indicated by markedly higher
      glycosaminoglycan release into conditioned medium. The combination of detrimental
      dynamic loading, nutrient deficiency, and TNF-alpha intradiscal injection can
      synergistically simulate the proinflammatory and degenerative disease condition
      within DDD. This model will be of high interest to screen therapeutic agents in
      further preclinical studies for early intervention and treatment of DDD.

PMID- 29320616
TI  - Epoxy Nanocomposites Filled with Carbon Nanoparticles.
AB  - Over the past decades, the development of high performance lightweight polymer
      nanocomposites and, in particular, of epoxy nanocomposites has become one the
      greatest challenges in material science. The ultimate goal of epoxy
      nanocomposites is to extrapolate the exceptional intrinsic properties of the
      nanoparticles to the bulk matrix. However, in spite of the efforts, this
      objective is still to be attained at commercially attractive scales. Key aspects
      to achieve this are ultimately the full understanding of network structure, the
      dispersion degree of the nanoparticles, the interfacial adhesion at the phase
      boundaries and the control of the localization and orientation of the
      nanoparticles in the epoxy system. In this Personal Account, we critically
      discuss the state of the art and evaluate the strategies to overcome these
      barriers.

PMID- 29320617
TI  - Gender-related differences in clinical presentation, electrocardiography signs,
      laboratory markers and outcome in patients with acute pulmonary embolism.
AB  - Background/Aim: Acute pulmonary embolism (PE) is a potentially life threating
      event, but there are scarce data about genderrelated differences in this
      condition. The aim of this study was to identify gender-specific differences in
      clinical presentation, the diagnosis and outcome between male and female patients
      with PE. Methods: We analysed the data of 144 consecutive patients with PE (50%
      women) and compared female and male patients regarding clinical presentation,
      electrocardiography (ECG) signs, basic laboratory markers and six-month outcome.
      All the patients confirmed PE by visualized thrombus on the multidetector
      computed tomography with pulmonary angiography (MDCTPA), ECG and
      echocardiographic examination at admission. Results: Compared to the men, the
      women were older and a larger proportion of them was in the third tertile of age
      (66.0% vs 34.0%, p = 0.008). In univariate analysis the men more often had
      hemoptysis [OR (95% CI) 3.75 (1.16-12.11)], chest pain [OR (95% CI) 3.31 (1.57
      7.00)] febrile state [OR (95% CI) 2.41 (1.12-5.22)] and pneumonia at PE
      presentation [OR (95% CI) 3.40 (1.25-9.22)] and less likely had heart
      decompensation early in the course of the disease [OR (95%CI) 0.48 (0.24-0.97)].
      In the multivariate analysis a significant difference in the rate of pneumonia
      and acute heart failure between genders disappeared due to strong influence of
      age. There was no significant difference in the occurrence of typical ECG signs
      for PE between the genders. Women had higher level of admission glycaemia [7.7
      mmol/L (5.5-8.2 mmol/L) vs 6.9 mmol/L (6.3-9.6 mmol/L), p = 0.006] and total
      number of leukocytes [10.5 x 109/L (8.8-12.7 x 109/L vs 8.7 x 109/L (7.0-11.6 x
      109/L)), p = 0.007]. There was a trend toward higher plasma level of brain
      natriuretic peptide in women compared to men 127.1 pg/mL (55.0-484.0 pg/mL), p =
      0.092] vs [90.3 pg/mL (39.2-308.5 pg/mL). The main 6-month outcomes, death and
      major bleeding, had similar frequencies in both sexes. Conclusion: There are
      several important differences between men and women in the clinical presentation
      of PE and basic laboratory findings which can influence the diagnosis and
      treatment of PE.

PMID- 29320618
TI  - Stenting versus non-stenting following uncomplicated ureteroscopic lithotripsy:
      Comparsion and evaluation of symptoms.
AB  - Background/Aim: Currently, ureterorenoscopic (URS) stone fragmentation and
      removal is the treatment of choice for managing ureteral stones, especially mid
      and distal ones and is advocated as initial management of ureteric stones. The
      aim of this work was to evaluate the symptoms, necessity, potential benefits and
      adverse effects of ureteral stent placement after uncomplicated ureteroscopic
      lithotripsy. Methods: This retrospective-prospective study evaluated a total of
      125 patients who had underwent ureteroscopic lithotripsy (URSL). The patients
      were divided into two groups: stented (59 patients) and unstented (controls, 66
      patients). The outcomes measured and compared between the two groups included:
      stone free rate, postoperative patient pain validated by scale, lower urinary
      tract symptoms (LUTS), the need for unplanned hospital care, stent related
      complications, and functional recovery in the form return to normal physical
      activities. Results: A successful outcome, defined as being stonefree after 12
      weeks, was achieved in all 125 (100%) patients. The stone-free rate showed no
      significant differences between the two groups. LUTS was frequent complaint in
      the stented group, with statistically significant difference in the domain of
      frequency/urgency (p = 0.0314). There was a statistically significant difference
      between the groups in the mean operative time and mean hospitalization time, mean
      pain visual analog scale (VAS) score and in the use of nonnarcotic analgesic. On
      the day of the surgery and until postoperative day 3 (POD 3) and postoperative
      day 5 (POD 5), the pain score was much higher among stented patients than among
      the controls (p = 0.0001) and non-narcotic analgesic use (p = 0.001) was
      frequently required in the stented group. Conclusion: Routine placement of
      ureteral stent after URSL is not mandatory and may be associated with stent side
      effects. Uncomplicated URSL is safe without stent placement after the treatment.

PMID- 29320619
TI  - Some specificities in the management of hyperglycemia in patients with diabetic
      kidney disease.

PMID- 29320620
TI  - Aortoesophageal and aortobronchial fistula caused by Candida albicans after
      thoracic endovascular aortic repair.
AB  - Introduction: Endovascular stent-graft placement has emerged as a minimally
      invasive alternative to open surgery for the treatment of aortic aneurysms and
      dissections. There are few reports of stent graft infections and aortoenteric
      fistula after endovascular thoracic aortic aneurysm repair, and the first
      multicentric study (Italian survey) showed the incidence of about 2%. Case
      report: We presented a 69-year-old male patient admitted to our hospital 9 months
      after thoracic endovascular aortic repair, due to severe chest pain in the left
      hemithorax and arm refractory to analgesic therapy. Multislice computed
      tomography (MSCT) showed a collection between the stent graft and the esophagus
      with thin layers of gas while gastroendoscopy showed visible blood jet 28 cm from
      incisive teeth. Surgical treatment was performed in collaboration of two teams
      (esophageal and vascular surgical team). After explantation of the stent graft
      and in situ reconstruction by using Dacron graft subsequent esophagectomy and
      graft omentoplasty were made. After almost four weeks patient developed
      hemoptisia as a sign of aorto bronchial fistula. Treatment with implantation of
      another aortic cuff of 26 mm was performed. The patient was discharged to the
      regional center with negative blood culture, normal inflammatory parameters and
      respiratory function. Three months later the patient suffered deterioration with
      the severe weight loss and pneumonia caused by Candida albicans and unfortunately
      died. The survival time from the surgical treatment of aortoesophageal fistula
      was 4 months Conclusion: Even if endovascular repair of thoracic aortic diseases
      improves early results, risk of infection should not be forgotten. Postoperative
      respiratory deterioration and finally hemoptisia could be the symptoms of another
      fistula.

PMID- 29320621
TI  - Central retinal vein occlusion: A patient with systemic sclerosis.
AB  - Introduction: Scleroderma (systemic sclerosis) is a severe chronic connective
      tissue disease, which results in involvement of numerous internal organs. Changes
      in the eye are the consequences of organ-specific manifestations of scleroderma
      or adverse effects of immunosuppressive treatment applied. Case report: We
      reported a 42-year-old woman with systemic sclerosis and acute deterioration of
      vision in the left eye, with visual acuity 0.9. After thorough clinical
      examination, including fluorescein angiography and optical coherence tomography,
      the diagnosis of nonischemic central retinal vein occlusion was made. Further
      biochemical, rheumatological and immunological investigation, apart from inactive
      systemic sclerosis, showed normal findings. Therefore, the cause of central
      retinal vein occlusion could only be attributed to the microvascular changes in
      systemic sclerosis. After three months, visual acuity deteriorated to 0.6 due to
      the development of cystoid macular edema. The patient received intravitreal
      injection of bevacizumab and after a single dose visual acuity improved to 0.9.
      After a 6- month follow-up, macular edema resolved and visual acuity stabilized.
      Conclusion: According to our knowledge and current data from the literature,
      central retinal vein occlusion is a rare vision threatening manifestation of
      scleroderma. There are only few published case reports on central vein occlusion
      in scleroderma patients. Examination of the ocular fundus is recommended for
      evaluation of vascular disease in patients with systemic sclerosis.

PMID- 29320622
TI  - Kartagener's syndrome: A case report.
AB  - Introduction: Kartagener's syndrome is a recessive autosomal disease which is
      mainly seen to affect ciliary movement. The symptoms of the syndrome are the
      consequence of the defective motility of the cilia found in the respiratory tract
      and that results with recurrent lung infections caused by mucus stasis in the
      bronchi. Case report: A 37-year-old married, male father of one child, presented
      with a history of productive cough, wheezing, dispnea, headache, temporary fever.
      In his 9th year of age, 1986, situs inversus, sinusitis and pectus excavatum were
      diagnosed. In 1994 he was operated for correction of pectus excavatum. Bronchial
      asthma was diagnosed in 2008 when he was 31. In the last 2 years he had episodes
      of breathlessness, wheezing, cough, expectoration, headache, fever and fast
      declining lung function. The patient was treated with combination of inhaled
      bronchodilatators (inhaled corticosteroids + long-acting beta-2 agonist), and
      occasional administration of antibiotics, oral prednisolone, mucolytics in
      episodes of exacerbations of disease over a period of 7-14 days. Conclusion:
      Treatment for patients with this syndrome has not been established yet, but it is
      important to control chronic lung infections and prevent declining of lung
      function.

PMID- 29320623
TI  - Primary hyperfibrinolysis as the presenting sign of prostate cancer: A case
      report.
AB  - Introduction: A bleeding syndrome in the setting of primary hyperfibrinolysis in
      a prostate cancer patient is only 0.40- 1.65% of cases. The laboratory diagnosis
      of primary hyperfibrinolysis is based on the increase of biomarkers like D-dimer,
      fibrinogen split products, plasminogen, and euglobulin lysis test. These tests
      are not specific for primary hyperfibrinolysis. We reported a rare case of
      hemorrhagic syndrome caused by primary hyperfibrinolysis as the first clinical
      symptom of metastatic prostate cancer. Case report: A 64-year-old male was
      admitted to our hospital with large hematomas in the right pectoral and axillary
      areas (20 x 7 cm), right hemiabdomen (30 x 30 cm) and the left lumbal area, (25 x
      5 cm). The patient had no subjective symptoms nor used any medication. Initial
      coagulation testing, prothrombin time (PT), and activated partial thromboplastin
      time (APTT) were within the normal range, while fibrinogen level was extremely
      low (1.068 g/L) (normal range 2.0-5.0) and the D-dimer assay result was high
      1.122 mg/L (normal range < 0.23). The results obtained by rotation
      thrombelastometry pointed to primary fibrinolysis. Further clinical and
      laboratory examination indicated progressive malignant prostate disease. First
      line treatment for the patient was a combined administration of tranexamic acid
      (3 x 500 mg iv) and transfusion of ten units of cryoprecipitate (400 mL). Next
      day, fibrinolytic function measurements by rotation thrombelastometry were within
      the normal ranges. Fibrinogen level was normalized within two days (2.4 g/L).
      There were no newly developed hematomas. Conclusion: This case report shows
      primary hyperfibrinolysis with bleeding symptoms, which is an uncommon
      paraneoplastic phenomenon within expanded prostate malignancy. Rotation
      thrombelastometry in this severe complication helped to achieve the prompt and
      proper diagnosis and treatment.

PMID- 29320624
TI  - Charles Bonnet syndrome.
AB  - Introduction: Charles Bonnet syndrome (CBS) is a condition that causes visual
      hallucinations in patients without any mental illnesses. CBS is characterized by
      the presence of vivid, complex and recurrent visual hallucinations, and do not
      occur in the setting or as part of delirium or other psychological illnesses. The
      condition is present in patients who have visual loss due to age-related macular
      degeneration (AMD), cataracts and/or other ocular diseases that influence vision.
      Case report: A 81-year-od woman reported to ophthalmologist complaining of visual
      hallucinations that consisted of white pigeons. Hallucinations were present for
      two years and she was well aware that hallucinations were unreal. Mental
      illnesses were excluded by the psychiatrist. Complete ophthalmologic examination
      was performed, and finding revealed visual acuity of 0.3 (right eye) and 0.5
      (left eye), in both eyes cataracts and AMD (wet form). Optical coherence
      tomography confirmed the fundoscopic finding of AMD. The patient rejected
      treatment of cataracts and AMD due to old age, and hallucinations persisted.
      Conclusion: CBS should be considered in patients with visual hallucinations and
      ocular diseases that influence vision. It is essential to distinguish CBS from
      mental illnesses, since patients with CBS are fully aware that hallucinations are
      not real. Awareness of CBS could help physicians upon referring patients to
      ophthalmologists instead of psychiatrists, and therefore avoid patients being
      misdiagnosed.

PMID- 29320625
TI  - Public health risk analysis through evaluation of drinking water safety.

PMID- 29320626
TI  - Directing Nanoparticle Biodistribution through Evasion and Exploitation of Stab2
      Dependent Nanoparticle Uptake.
AB  - Up to 99% of systemically administered nanoparticles are cleared through the
      liver. Within the liver, most nanoparticles are thought to be sequestered by
      macrophages (Kupffer cells), although significant nanoparticle interactions with
      other hepatic cells have also been observed. To achieve effective cell-specific
      targeting of drugs through nanoparticle encapsulation, improved mechanistic
      understanding of nanoparticle-liver interactions is required. Here, we show the
      caudal vein of the embryonic zebrafish ( Danio rerio) can be used as a model for
      assessing nanoparticle interactions with mammalian liver sinusoidal (or
      scavenger) endothelial cells (SECs) and macrophages. We observe that anionic
      nanoparticles are primarily taken up by SECs and identify an essential
      requirement for the scavenger receptor, stabilin-2 ( stab2) in this process.
      Importantly, nanoparticle-SEC interactions can be blocked by dextran sulfate, a
      competitive inhibitor of stab2 and other scavenger receptors. Finally, we exploit
      nanoparticle-SEC interactions to demonstrate targeted intracellular drug delivery
      resulting in the selective deletion of a single blood vessel in the zebrafish
      embryo. Together, we propose stab2 inhibition or targeting as a general approach
      for modifying nanoparticle-liver interactions of a wide range of nanomedicines.

PMID- 29320627
TI  - Wafer-Scale Ultrathin Two-Dimensional Conjugated Microporous Polymers:
      Preparation and Application in Heterostructure Devices.
AB  - In this work, we report a universal surface-assisted oxidative polymerization
      strategy for wafer-scale fabrication of ultrathin two-dimensional conjugated
      microporous polymers (2D CMPs) on arbitrary substrates under ambient conditions.
      Three kinds of 2D CMPs with average thickness of 1.5-3.6 nm were prepared on
      SiO2/Si substrates by using carbazole based monomers. Moreover, 2D CMPs can be
      grown on reduced graphene oxide (rGO) substrate to construct large-area 2D
      CMP/rGO heterostructure. As a proof-of-concept demonstration, an organic vertical
      field-effect transistor based on 2D CMP/rGO heterostructures was fabricated,
      which exhibited typical p-type behavior with high reproducibility and on/off
      current ratio. Most importantly, the direct growth of large-area 2D CMPs on
      arbitrary substrates is compatible with the conventional processes in the
      semiconductor industry, and therefore is expected to expedite the development of
      2D CMPs as building blocks for construction of practical electronic devices.

PMID- 29320628
TI  - Assessing GW Approaches for Predicting Core Level Binding Energies.
AB  - Here we present a systematic study on the performance of different GW approaches:
      G0W0, G0W0 with linearized quasiparticle equation (lin-G0W0), and quasiparticle
      self-consistent GW (qsGW), in predicting core level binding energies (CLBEs) on a
      series of representative molecules comparing to Kohn-Sham (KS) orbital energy
      based results. KS orbital energies obtained using the PBE functional are 20-30 eV
      lower in energy than experimental values obtained from X-ray photoemission
      spectroscopy (XPS), showing that any Koopmans-like interpretation of KS core
      level orbitals fails dramatically. Results from qsGW lead to CLBEs that are
      closer to experimental values from XPS, yet too large. For the qsGW method, the
      mean absolute error is about 2 eV, an order of magnitude better than plain KS PBE
      orbital energies and quite close to predictions from DeltaSCF calculations with
      the same functional, which are accurate within ~1 eV. Smaller errors of ~0.6 eV
      are found for qsGW CLBE shifts, again similar to those obtained using DeltaSCF
      PBE. The computationally more affordable G0W0 approximation leads to results less
      accurate than qsGW, with an error of ~9 eV for CLBEs and ~0.9 eV for their
      shifts. Interestingly, starting G0W0 from PBE0 reduces this error to ~4 eV with a
      slight improvement on the shifts as well (~0.4 eV). The validity of the G0W0
      results is however questionable since only linearized quasiparticle equation
      results can be obtained. The present results pave the way to estimate CLBEs in
      periodic systems where DeltaSCF calculations are not straightforward although
      further improvement is clearly needed.

PMID- 29320629
TI  - The Structural Asymmetry of Mitochondrial Hsp90 (Trap1) Determines Fine Tuning of
      Functional Dynamics.
AB  - The Hsp90 family of molecular chaperones oversees the folding of a wide range of
      client proteins. Hsp90 is a homodimer, whose conformational states and functions
      are regulated by ATP-binding and hydrolysis. The crystal structure of
      mitochondrial Hsp90 (Trap1) showed that one of the two protomers in the active
      state is buckled, resulting in an asymmetric conformation. The asymmetry between
      the two protomers corresponds to the broadly conserved region responsible for
      client binding. Moreover, asymmetry determines differential hydrolysis for each
      protomer, with the buckled conformation favoring ATP processing. Experimental
      results show that after the first hydrolysis the dimer flips to a different
      asymmetric state while remaining in a closed conformation for the second
      hydrolysis. In this model, asymmetry plays a key role in the mechanism that
      drives chaperone function. Herein, we investigate the nucleotide-dependent
      internal dynamics of Trap1 with computational approaches. Our results shed light
      on the relationship between the nucleotide state in the N-terminal domain and the
      asymmetric modulation of the dynamic and structural properties of the client
      binding region in the Middle domain. According to our analysis, this is the
      region that undergoes the most intense dynamic modulation upon nucleotide
      exchange. This result provides molecular insights into the roles of structural
      asymmetry in the regulation of Trap1 and suggests that this substructure is a
      promising target to modulate the functionally oriented aspects of Trap1 dynamics,
      therefore opening fresh opportunities for the design of selective therapeutics
      for Trap1-dependent diseases.

PMID- 29320630
TI  - Structural Insight into the Discrimination between 8-Oxoguanine Glycosidic
      Conformers by DNA Repair Enzymes: A Molecular Dynamics Study of Human Oxoguanine
      Glycosylase 1 and Formamidopyrimidine-DNA Glycosylase.
AB  - hOgg1 and FPG are the primary DNA repair enzymes responsible for removing the
      major guanine (G) oxidative product, namely, 7,8-dihydro-8-oxoguanine (OG), in
      humans and bacteria, respectively. While natural G adopts the anti conformation
      and forms a Watson-Crick pair with cytosine (C), OG can also adopt the syn
      conformation and form a Hoogsteen pair with adenine (A). hOgg1 removes OG paired
      with C but is inactive toward the OG:A pair. In contrast, FPG removes OG from
      OG:C pairs and also exhibits appreciable (although diminished) activity toward
      OG:A pairs. As a first step toward understanding this difference in activity, we
      have employed molecular dynamics simulations to examine how the anti and syn
      conformers of OG are accommodated in the hOgg1 and FPG active sites. When anti-OG
      is bound, hOgg1 active site residues are properly aligned to initiate catalytic
      base departure, while geometrical parameters required for the catalytic reaction
      are not conserved for syn-OG. On the other hand, the FPG catalytic residues are
      suitably aligned for both OG conformers, with anti-OG being more favorably bound.
      Thus, our data suggests that the differential ability of hOgg1 and FPG to
      accommodate the anti- and syn-OG glycosidic conformations is an important factor
      that contributes to the relative experimental excision rates. Nevertheless, the
      positions of the nucleophiles with respect to the lesion in the active sites
      suggest that the reactant complex is poised to initiate catalysis through a
      similar mechanism for both repair enzymes and supports a recently proposed
      mechanism in which sugar-ring opening precedes nucleoside deglycosylation.

PMID- 29320631
TI  - Thermoresponsive- co-Biodegradable Linear-Dendritic Nanoparticles for Sustained
      Release of Nerve Growth Factor To Promote Neurite Outgrowth.
AB  - Thermoresponsive and biodegradable linear-dendritic nanoparticles containing
      poly( N-isopropylacrylamide), poly(l-lactic acid), and poly(l-lysine) dendrons
      were investigated for sustained release of nerve growth factor (NGF) in response
      to temperature change. The nanoparticles and their degradants were not cytotoxic
      to neuron-like PC12 cells for at least one month. The nanoparticles were
      preferentially taken up by PC12 cells 6-13-times more at temperatures above (37 
      degrees C) than below (25  degrees C) the lower critical solution temperature of
      the nanoparticles. NGF could be loaded into the nanoparticles in aqueous solution
      and slowly released from the nanoparticles for 12 and 33 days at 25 and 37 
      degrees C, respectively. The released NGF was biologically active by promoting
      neurite outgrowth of PC12 cells. This work demonstrates a new concept of using
      thermoresponsive and biodegradable linear-dendritic nanoparticles for thermally
      targeted and sustained release of NGF and other protein drugs for the treatment
      of Alzheimer's disease and other neurological disorders.

PMID- 29320633
TI  - Bioaccumulation of Polybrominated Diphenyl Ethers and Alternative Halogenated
      Flame Retardants in a Vegetation-Caribou-Wolf Food Chain of the Canadian Arctic.
AB  - The trophodynamics of halogenated flame retardants (HFRs) including
      polybrominated diphenyl ethers (PBDEs) and alternative HFRs were investigated in
      the terrestrial, vegetation-caribou-wolf food chain in the Bathurst Region of
      northern Canada. The greatest concentrations in vegetation (geometric mean of
      lichens, moss, grasses, willow, and mushrooms) were of the order 2,4,6
      tribromophenyl allyl ether (TBP-AE) (10 ng g-1 lw) > BDE47 (5.5 ng g-1 lw) >
      BDE99 (3.9 ng g-1 lw) > BDE100 (0.82 ng g-1 lw) > 1,2,3,4,5-pentabromobenzene
      (PBBz) (0.72 ng g-1 lw). Bioconcentration among types of vegetation was
      consistent, though it was typically greatest in rootless vegetation (lichens,
      moss). Biomagnification was limited in mammals; only BDE197, BDE206-208 and ?PBDE
      biomagnified to caribou from vegetation [biomagnification factors (BMFs) = 2.0
      5.1]. Wolves biomagnified BDE28/33, BDE153, BDE154, BDE206, BDE207, and ?PBDE
      significantly from caribou (BMFs = 2.9-17) but neither mammal biomagnified any
      alternative HFRs. Only concentrations of BDE28/33, BDE198, nonaBDEs, and ?PBDE
      increased with trophic level, though the magnitude of biomagnification was low
      relative to legacy, recalcitrant organochlorine contaminants [trophic
      magnification factors (TMFs) = 1.3-1.8]. Despite bioaccumulation in vegetation
      and mammals, the contaminants investigated here exhibited limited
      biomagnification potential and remained at low parts per billion concentrations
      in wolves.

PMID- 29320632
TI  - Increasing the Stability of Recombinant Human Green Cone Pigment.
AB  - Three types of cone cells exist in the human retina, each containing a different
      pigment responsible for the initial step of phototransduction. These pigments are
      distinguished by their specific absorbance maxima: 425 nm (blue), 530 nm (green),
      and 560 nm (red). Each pigment contains a common chromophore, 11-cis-retinal
      covalently bound to an opsin protein via a Schiff base. The 11-cis-retinal
      protonated Schiff base has an absorbance maxima at 440 nm in methanol.
      Unfortunately, the chemistry that allows the same chromophore to interact with
      different opsin proteins to tune the absorbance of the resulting pigments to
      distinct lambdamax values is poorly understood. Rhodopsin is the only pigment
      with a native structure determined at high resolution. Homology models for cone
      pigments have been generated, but experimentally determined structures are needed
      for a precise understanding of spectral tuning. The principal obstacle to solving
      the structures of cone pigments has been their innate instability in recombinant
      constructs. By inserting five different thermostabilizing proteins (BRIL, T4L,
      PGS, RUB, and FLAV) into the recombinant green opsin sequence, constructs were
      created that were up to 9-fold more stable than WT. Using cellular retinaldehyde
      binding protein (CRALBP), we developed a quick means of assessing the stability
      of the green pigment. CRALBP testing also confirmed an additional 48-fold
      increase in pigment stability when varying the detergent used. These results
      suggest an efficient protocol for routine purification and stabilization of cone
      pigments that could be used for high-resolution determination of their
      structures, as well as for other studies.

PMID- 29320634
TI  - Continuously Tuning Epitaxial Strains by Thermal Mismatch.
AB  - Strain engineering of thin films is a conventionally employed approach to enhance
      material properties and to energetically prefer ground states that would
      otherwise not be attainable. Controlling strain states in perovskite oxide thin
      films is usually accomplished through coherent epitaxy by using lattice
      mismatched substrates with similar crystal structures. However, the limited
      choice of suitable oxide substrates makes certain strain states experimentally
      inaccessible and a continuous tuning impossible. Here, we report a strategy to
      continuously tune epitaxial strains in perovskite films grown on Si(001) by
      utilizing the large difference of thermal expansion coefficients between the film
      and the substrate. By establishing an adsorption-controlled growth window for
      SrTiO3 thin films on Si using hybrid molecular beam epitaxy, the magnitude of
      strain can be solely attributed to thermal expansion mismatch, which only depends
      on the difference between growth and room temperature. Second-harmonic generation
      measurements revealed that structure properties of SrTiO3 films could be tuned by
      this method using films with different strain states. Our work provides a
      strategy to generate continuous strain states in oxide/semiconductor
      pseudomorphic buffer structures that could help achieve desired material
      functionalities.

PMID- 29320636
TI  - How do London Dispersion Interactions Impact the Photochemical Processes of
      Molecular Switches?
AB  - In the last two decades, linear-response time-dependent density functional theory
      (LR-TDDFT) has become one of the most widely used approaches for the computation
      of the excited-state properties of atoms and molecules. Despite its success in
      describing the photochemistry and the photophysics of a vast majority of
      molecular systems, its domain of applicability has been limited by several
      substantial drawbacks. Commonly identified problems of LR-TDDFT include the
      correct description of Rydberg states, charge-transfer excited states, doubly
      excited states, and nearly degenerate states. In addition to these widely
      recognized shortcomings, the approximate functionals used in LR-TDDFT are unable
      to fully describe London dispersion interactions. In this work, we aim at
      understanding the impact of van der Waals interactions on the properties of
      chemical systems beyond their electronic ground state. For this purpose, we
      compare the results of excited-state energy profiles and dynamic trajectories for
      the prototypical cis-stilbene molecule with its 3-3',5-5'-tetra-tert-butyl
      derivative. While the explicit treatment of London dispersion interactions
      results in negligible changes for the cis-stilbene, we show that these attractive
      forces have a substantial influence on the energetics and structural evolution of
      the substituted derivative. In the latter case, intramolecular dispersion
      interactions impact the outcome of the simulation qualitatively, leading to an
      increased preference for the photocyclization pathway. The methodological
      consequences of this work are not uniquely applicable to the illustrative
      stilbene case. In fact, this molecule is representative of a whole class of
      chemical situations, where dispersion forces dominate the interactions between
      the unexcited substituents of a photoexcited chromophore. This is, for instance,
      a common situation in organic photovoltaics where donor molecules are usually
      functionalized with long alkyl side chains to improve solubility and assembly.

PMID- 29320635
TI  - Extending the Propagation Distance of a Silver Nanowire Plasmonic Waveguide with
      a Dielectric Multilayer Substrate.
AB  - Chemical-synthesized silver nanowires have been proven as an efficient
      architecture for plasmonic waveguides, but the high propagation loss prevents
      their widely applications. Here, we demonstrate that the propagation distance of
      the plasmons along a silver nanowire can be extended if this nanowire was placed
      on a dielectric multilayer substrate containing a photonic band gap but not
      placed on a commonly used glass substrate. The propagation distance at 630 nm
      wavelength can reach 16 MUm, even when the silver nanowire is as thin as 90 nm in
      diameter. Experimental and simulation results further show that the polarization
      of this propagating plasmon mode was nearly parallel to the surface of the
      dielectric multilayer, so it can be excited by a transverse-electric polarized
      Bloch surface wave propagating along a polymer nanowire with diameter at only
      about 170 nm on the same dielectric multilayer. Numerical simulations were also
      carried out and are consistent with the experiment results. Our work provides a
      platform with which to extend the propagation distance of the plasmonic waveguide
      and also for the integration between photonic and plasmonic waveguides on the
      nanometer scale.

PMID- 29320637
TI  - Rejuvenating Regenerative Medicine Regulation.

PMID- 29320638
TI  - What Do We Rate When We Rate Our Health? Decomposing Age-related Contributions to
      Self-rated Health.
AB  - Self-ratings of health (SRH) indicate current health-related quality of life and
      independently predict mortality. Studies show the SRH of older adults appears
      less influenced by physical health than the SRH of younger adults. But if
      physical health accounts less for the SRH of older adults, what factors take its
      place? To understand the relative contributions of social, emotional, and
      physical states to SRH by age, we analyzed data from the National Health
      Interview Survey 2006 to 2011 ( N = 153,341). In age-stratified regressions,
      physical health and functional limitations declined as correlates of SRH for
      older age strata, while social factors, such as gender and race, increased in
      importance. Oaxaca-Blinder decomposition showed that if younger respondents had
      similar health conditions, they would rate their health more poorly than current
      cohorts of older adults do. The declining influence of physical health on SRH in
      old age appears to be due in part to displacement by social factors.

PMID- 29320639
TI  - Minimally Invasive Distal Metatarsal Metaphyseal Osteotomy (DMMO) of the Fifth
      Metatarsal for Bunionette Correction.
AB  - BACKGROUND: Different osteotomies have been proposed for the treatment of
      bunionette deformity. Minimally invasive surgery is now increasingly popular for
      a variety of forefoot conditions. The aim of this study was to evaluate the
      outcome following fifth minimally invasive distal metatarsal metaphyseal
      osteotomy (DMMO) for bunionette deformity. METHODS: Nineteen patients (21 feet)
      who had symptomatic bunionette deformity and failed conservative treatment
      between 2014 and 2016 were included in this retrospective study. Clinical data
      were recorded, and pre- and postoperative Manchester-Oxford Foot Questionnaire
      (MOXFQ) scores and visual analog scale (VAS) pain score were collected. The mean
      follow-up was 28 months (range, 12-47). RESULTS: The mean MOXFQ summary index
      score decreased from 71 (range, 59-81) preoperatively to 10 (range, 0-30)
      postoperatively. All 3 MOXFQ domains also improved. The average improvement in
      VAS score was 7. Forefoot swelling and some painful symptoms took an average of 3
      months to settle. There were no wound or nerve complications. One patient
      required a dorsal cheilectomy for a symptomatic prominent dorsolateral callus
      formation. CONCLUSION: The minimally invasive fifth DMMO for bunionette deformity
      was a safe and effective technique. It had relatively few complications and led
      to good clinical results. We believe it is important to warn patients that the
      forefoot swelling will take months to settle compared to an osteotomy with
      fixation, and there is a 10% chance of a prominent callus over the osteotomy
      site. LEVEL OF EVIDENCE: Level IV, retrospective case series.

PMID- 29320640
TI  - Syme Amputation: A Systematic Review.
AB  - BACKGROUND: In the decision-making process toward an amputation of the lower
      extremity, knowledge about patient-related outcomes after amputation and
      rehabilitation is important. We have not found a systematic review that provides
      this knowledge for Syme amputation. The aim of this study was to present an
      overview of outcomes after a Syme amputation grouped according to the
      International Classification of Functioning, Disability and Health (ICF) model,
      focusing on body structures and functions, activities, and participation.
      METHODS: A systematic literature search was performed. Included studies went
      through 2 selection procedures by 2 independent assessors. Included were all
      studies concerning Syme amputation with patient-related outcomes. RESULTS: Thirty
      six studies were included for data extraction, concerning 1056 patients (238
      children and 818 adults). Heel pad migration was reported in 49 of 176 (28%),
      skin problems in 23 of 128 (18%), and bone problems in 42 of 145 (29%) children.
      No reamputations were reported. All children were fitted with a prosthesis, and
      62 of 90 (69%) children participated in sports. Skin problems were reported in 35
      of 195 (18%), ulceration or infection in 120 of 512 (23%), residual limb pain in
      46 of 181 (25%), and reamputations in 180 of 919 (20%) adults. In total, 247 of
      363 (68%) adults were fitted with a prosthesis. Walking aids were used by 45 of
      135 (33%) adults. Employment status was unchanged in 147 of 209 (72%) adults.
      CONCLUSION: In children, no reamputations were necessary and few complications
      were reported, with good participation in daily life in the majority of children.
      In adults, more complications and reamputations were reported; nevertheless, most
      adult amputees became successful prosthesis users. LEVEL OF EVIDENCE: Therapeutic
      Level III, systematic review containing retrospective cohort studies.

PMID- 29320641
TI  - AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF
      ENDOCRINOLOGY POSITION STATEMENT ON TESTING FOR AUTONOMIC AND SOMATIC NERVE
      DYSFUNCTION.
AB  - This document represents the official position of the American Association of
      Clinical Endocrinologists and the American College of Endocrinology. Where there
      were no randomized controlled trials or specific U.S. FDA labeling for issues in
      clinical practice, the participating clinical experts utilized their judgment and
      experience. Every effort was made to achieve consensus among the committee
      members. Position statements are meant to provide guidance, but they are not to
      be considered prescriptive for any individual patient and cannot replace the
      judgment of a clinician.

PMID- 29320642
TI  - ENDOCRINE TREATMENT OF GENDER-DYSPHORIC/GENDER-INCONGRUENT PERSONS: AN ENDOCRINE
      SOCIETY CLINICAL PRACTICE GUIDELINE.

PMID- 29320644
TI  - CORRECTION.

PMID- 29320643
TI  - 2017 AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS/ENDOCRINE SOCIETY UPDATE
      ON TRANSGENDER MEDICINE: CASE DISCUSSIONS.
AB  - OBJECTIVE: Increased numbers of transgender and gender-nonconforming people are
      presenting to physicians in the United States and abroad due to increased public
      recognition and acceptance and increased access to healthcare facilities.
      However, there are still gaps in medical knowledge among endocrinologists and
      other health care professionals. The purpose of these cases is to present several
      common clinical vignettes of transgender people presenting in an office setting
      that illustrate some of the key recommendations of the Endocrine Society's
      revised Endocrine Treatment of Gender Dysphoria/Gender Incongruent Persons
      guidelines, cosponsored by the American Association of Clinical Endocrinologists.
      METHODS: Cases were developed based on these recently revised guidelines for
      gender-dysphoric and gender-nonconforming persons. RESULTS: Six cases are
      presented that illustrate the diagnosis, treatment, and long-term management of
      trans-gender children and adults based on the revised guidelines for the
      endocrine care of gender-dysphoric and gender-nonconforming persons. Several key
      teaching points are presented from the presentation of these cases. CONCLUSION:
      Endocrinologists should be familiar with the revised guidelines for gender
      dysphoric and gender-nonconforming persons. Important aspects of care are the
      diagnosis of gender dysphoria, the timing of treatment with gender-affirming
      hormones, and the long-term monitoring for potential adverse outcomes. Long-term
      health outcome studies are needed to further help guide care in this unique
      population. ABBREVIATIONS: BMI = body mass index GnRH = gonadotropin-releasing
      hormone HDL = high-density lipoprotein LDL = low-density lipoprotein.

PMID- 29320645
TI  - LETTER TO THE EDITOR.

PMID- 29320646
TI  - Transfer of Fresh versus Frozen Embryos in Ovulatory Women.
AB  - BACKGROUND: Elective frozen-embryo transfer has been shown to result in a higher
      live-birth rate than fresh-embryo transfer among anovulatory women with the
      polycystic ovary syndrome. It is uncertain whether frozen-embryo transfer
      increases live-birth rates among ovulatory women with infertility. METHODS: In
      this multicenter, randomized trial, we randomly assigned 2157 women who were
      undergoing their first in vitro fertilization cycle to undergo either fresh
      embryo transfer or embryo cryopreservation followed by frozen-embryo transfer. Up
      to two cleavage-stage embryos were transferred in each participant. The primary
      outcome was a live birth after the first embryo transfer. RESULTS: The live-birth
      rate did not differ significantly between the frozen-embryo group and the fresh
      embryo group (48.7% and 50.2%, respectively; relative risk, 0.97; 95% confidence
      interval [CI], 0.89 to 1.06; P=0.50). There were also no significant between
      group differences in the rates of implantation, clinical pregnancy, overall
      pregnancy loss, and ongoing pregnancy. Frozen-embryo transfer resulted in a
      significantly lower risk of the ovarian hyperstimulation syndrome than fresh
      embryo transfer (0.6% vs. 2.0%; relative risk, 0.32; 95% CI, 0.14 to 0.74;
      P=0.005). The risks of obstetrical and neonatal complications and other adverse
      outcomes did not differ significantly between the two groups. CONCLUSIONS: The
      live-birth rate did not differ significantly between fresh-embryo transfer and
      frozen-embryo transfer among ovulatory women with infertility, but frozen-embryo
      transfer resulted in a lower risk of the ovarian hyperstimulation syndrome.
      (Funded by the National Key Research and Development Program of China and the
      National Natural Science Foundation of China; Chinese Clinical Trial Registry
      number, ChiCTR-IOR-14005406 .).

PMID- 29320648
TI  - Canakinumab for Atherosclerotic Disease.

PMID- 29320650
TI  - Cowpox Virus Infection.

PMID- 29320649
TI  - Romosozumab versus Alendronate and Fracture Risk in Women with Osteoporosis.

PMID- 29320651
TI  - Oxygen Therapy in Suspected Acute Myocardial Infarction.

PMID- 29320647
TI  - Long-Term Effects of Inhaled Budesonide for Bronchopulmonary Dysplasia.
AB  - BACKGROUND: The long-term effects on neurodevelopment of the use of inhaled
      glucocorticoids in extremely preterm infants for the prevention or treatment of
      bronchopulmonary dysplasia are uncertain. METHODS: We randomly assigned 863
      infants (gestational age, 23 weeks 0 days to 27 weeks 6 days) to receive early
      (within 24 hours after birth) inhaled budesonide or placebo. The prespecified
      secondary long-term outcome was neurodevelopmental disability among survivors,
      defined as a composite of cerebral palsy, cognitive delay (a Mental Development
      Index score of <85 [1 SD below the mean of 100] on the Bayley Scales of Infant
      Development, Second Edition, with higher scores on the scale indicating better
      performance), deafness, or blindness at a corrected age of 18 to 22 months.
      RESULTS: Adequate data on the prespecified composite long-term outcome were
      available for 629 infants. Of these infants, 148 (48.1%) of 308 infants assigned
      to budesonide had neurodevelopmental disability, as compared with 165 (51.4%) of
      321 infants assigned to placebo (relative risk, adjusted for gestational age,
      0.93; 95% confidence interval [CI], 0.80 to 1.09; P=0.40). There was no
      significant difference in any of the individual components of the prespecified
      outcome. There were more deaths in the budesonide group than in the placebo group
      (82 [19.9%] of 413 infants vs. 58 [14.5%] of 400 infants for whom vital status
      was available; relative risk, 1.37; 95% CI, 1.01 to 1.86; P=0.04). CONCLUSIONS:
      Among surviving extremely preterm infants, the rate of neurodevelopmental
      disability at 2 years did not differ significantly between infants who received
      early inhaled budesonide for the prevention of bronchopulmonary dysplasia and
      those who received placebo, but the mortality rate was higher among those who
      received budesonide. (Funded by the European Union and Chiesi Farmaceutici;
      ClinicalTrials.gov number, NCT01035190 .).

PMID- 29320652
TI  - Multiple Sclerosis.

PMID- 29320653
TI  - In-Person Health Care as Option B.

PMID- 29320654
TI  - Immune-Related Adverse Events Associated with Immune Checkpoint Blockade.

PMID- 29320655
TI  - IVF Transfer of Fresh or Frozen Embryos in Women without Polycystic Ovaries.
AB  - BACKGROUND: Among women who are undergoing in vitro fertilization (IVF), the
      transfer of frozen embryos has been shown to result in a higher rate of live
      birth than the transfer of fresh embryos in those with infertility associated
      with the polycystic ovary syndrome. It is not known whether frozen-embryo
      transfer results in similar benefit in women with infertility that is not
      associated with the polycystic ovary syndrome. METHODS: We randomly assigned 782
      infertile women without the polycystic ovary syndrome who were undergoing a first
      or second IVF cycle to receive either a frozen embryo or a fresh embryo on day 3.
      In the frozen-embryo group, all grade 1 and 2 embryos had been cryopreserved, and
      a maximum of two embryos were thawed on the day of transfer in the following
      cycle. In the fresh-embryo group, a maximum of two fresh embryos were transferred
      in the stimulated cycle. The primary outcome was ongoing pregnancy after the
      first embryo transfer. RESULTS: After the first completed cycle, ongoing
      pregnancy occurred in 142 of 391 women (36.3%) in the frozen-embryo group and in
      135 of 391 (34.5%) in the fresh-embryo group (risk ratio in the frozen-embryo
      group, 1.05; 95% confidence interval [CI], 0.87 to 1.27; P=0.65). Rates of live
      birth after the first transfer were 33.8% and 31.5%, respectively (risk ratio,
      1.07; 95% CI, 0.88 to 1.31). CONCLUSIONS: Among infertile women without the
      polycystic ovary syndrome who were undergoing IVF, the transfer of frozen embryos
      did not result in significantly higher rates of ongoing pregnancy or live birth
      than the transfer of fresh embryos. (Funded by My Duc Hospital;
      ClinicalTrials.gov number, NCT02471573 .).

PMID- 29320656
TI  - Electrolyte Disturbances in Chronic Alcohol-Use Disorder.

PMID- 29320657
TI  - Case 1-2018. A 39-Year-Old Woman with Rapidly Progressive Respiratory Failure.

PMID- 29320658
TI  - Osimertinib as First-Line Treatment in EGFR-Mutated Non-Small-Cell Lung Cancer.

PMID- 29320659
TI  - Iris Abscess.

PMID- 29320660
TI  - Nicotine replacement therapy for smoking cessation during pregnancy.
AB  - Nicotine replacement therapy (NRT) is recommended in current Australian clinical
      guidelines for pregnant women who are unable to quit smoking unassisted.
      Clinicians report low levels of prescribing NRT during pregnancy, due to safety
      concerns and low levels of confidence in their ability to prescribe NRT. Animal
      models show that nicotine is harmful to the fetus, especially for brain and lung
      development, but human studies have not found any harmful effects on fetal and
      pregnancy outcomes. Studies of efficacy and effectiveness in the real world
      suggest that NRT use during pregnancy increases smoking cessation rates. These
      rates may be hampered by the fact that studies so far have used an NRT dose that
      does not adequately account for the higher nicotine metabolism during pregnancy
      and, therefore, does not adequately treat withdrawal symptoms. Further research
      is needed to assess the safety and efficacy of higher dosages of NRT in
      pregnancy, specifically of combination treatment using dual forms of NRT. As NRT
      is safer than smoking, clinicians need to offer this option to all pregnant women
      who smoke. A practical guide for initiating and tailoring the dose of NRT in
      pregnancy is suggested.

PMID- 29320661
TI  - Regulating e-cigarettes in Australia: implications for tobacco use by young
      people.

PMID- 29320663
TI  - Investing in men's health in Australia.

PMID- 29320664
TI  - Distributions and what to do when they are non-normal.

PMID- 29320665
TI  - A guide to improving women's health.

PMID- 29320666
TI  - The value of novel oral anticoagulants in rural Australia.

PMID- 29320667
TI  - Surviving breast cancer.

PMID- 29320668
TI  - The impact of non-vitamin K antagonist oral anticoagulants (NOACs) on
      anticoagulation therapy in rural Australia.
AB  - OBJECTIVE: To determine the use of different anticoagulation therapies in rural
      Western Australia; to establish whether remoteness from health care services
      affects the choice of anticoagulation therapy; to gather preliminary data on
      anticoagulation therapy safety and efficacy. DESIGN: Retrospective cohort study
      of patients hospitalised with a principal diagnosis of atrial
      fibrillation/flutter (AF) or venous thromboembolism (VTE) during 2014-2015.
      SETTING: Four hospitals serving two-thirds of the rural population of Western
      Australia. PARTICIPANTS: 609 patients with an indication for anticoagulation
      therapy recorded in their hospital discharge summary for index admission. MAIN
      OUTCOME MEASURES: Prescribing rates of anticoagulation therapies by indication
      for anticoagulation and distance of patient residence from their hospital. The
      primary safety outcome was re-hospitalisation with a major or clinically relevant
      non-major bleeding event; the primary lack-of-efficacy outcome was re
      hospitalisation for a thromboembolic event. RESULTS: The overall rates of
      prescription of NOACs and warfarin were similar (34% v 33%). A NOAC was
      prescribed more often than warfarin for patients with AF (56.0% v 42.2% of those
      who received an anticoagulant; P < 0.001), but less often for patients with VTE
      (29% v 48%; P < 0.001). Warfarin was prescribed for 38% of patients who lived
      locally, a NOAC for 31% (P = 0.013); for non-local patients, the respective
      proportions were 29% and 36% (P = 0.08). 69% of patients with AF and a CHA2DS2
      VASc score >= 1 were prescribed anticoagulation therapy. Patients treated with
      NOACs had fewer bleeding events than patients treated with warfarin (nine events
      [4%] v 20 events [10%]; P = 0.027). CONCLUSIONS: In rural WA, about one-third of
      patients with an indication for anticoagulation therapy receive NOACs, but one
      third of patients with AF and at risk of stroke received no anticoagulant
      therapy, and may benefit from NOAC therapy.

PMID- 29320669
TI  - Comorbidities in Australian women with hormone-dependent breast cancer: a
      population-based analysis.
AB  - OBJECTIVE: To compare how frequently selected chronic diseases developed in women
      with breast cancer receiving endocrine therapy, and in women without cancer.
      DESIGN, SETTING AND PARTICIPANTS: Retrospective, rolling cohort study, analysing
      a random 10% sample of Pharmaceutical Benefits Scheme (PBS) data for the period 1
      January 2003 - 31 December 2014. Women with breast cancer who first commenced
      endocrine therapy between January 2004 and December 2011 were identified, and age
      and sex-matched (1:10) by comorbidity with control groups of women who did not
      have a dispensing record for antineoplastic agents during the study period or the
      comorbidity of interest at baseline. MAIN OUTCOME MEASURES: Development of any of
      eight pre-selected comorbidities, identified in PBS claims data with the RxRisk-V
      model. RESULTS: Women with hormone-dependent breast cancer were significantly
      more likely than women in the control group to develop depression (overall hazard
      ratio [HR], 1.36; 95% CI, 1.26-1.46), pain or pain-inflammation (HR, 1.30; 95%
      CI, 1.23-1.38), osteoporosis (overall HR, 1.27; 95% CI, 1.17-1.39), diabetes (HR,
      1.24; 95% CI, 1.10-1.41), cardiovascular disorders (overall HR, 1.22; 95% CI,
      1.13-1.32), and gastric acid disorders (HR, 1.20; 95% CI, 1.13-1.28). The hazard
      ratios for developing cardiovascular disorders, depression and osteoporosis were
      highest during the first year of endocrine therapy. The risk of hyperlipidaemia
      was lower among women with breast cancer than in the control group (HR, 0.88; 95%
      CI, 0.81-0.96). There was no significant difference between the two groups in the
      risk of reactive airway diseases (HR, 1.05; 95% CI, 0.98-1.13). CONCLUSION:
      Comorbid conditions are more likely to develop in women who have been diagnosed
      with hormone-dependent breast cancer than in women without cancer. Our results
      further support the need to develop appropriate models of care to manage the
      multiple chronic disorders of breast cancer survivors.

PMID- 29320670
TI  - Diagnosing COPD and supporting smoking cessation in general practice: evidence
      practice gaps.
AB  - OBJECTIVES: To review the accuracy of diagnoses of chronic obstructive pulmonary
      disease (COPD) in primary care in Australia, and to describe smokers' experiences
      with and preferences for smoking cessation. DESIGN, SETTING AND PARTICIPANTS:
      Patients were invited to participate if they were at least 40 years old and had
      visited participating general practice clinics in Melbourne at least twice during
      the previous 12 months, reported being current or ex-smokers with a smoking
      history of at least 10 pack-years, or were being managed for COPD. Interviews
      based on a structured questionnaire and case finding (FEV1/FEV6 measurement) were
      followed, when appropriate, by spirometry testing and assessment of health
      related quality of life, dyspnoea and symptoms. RESULTS: 1050 patients attended
      baseline interviews (February 2015 - April 2017) at 41 practices. Of 245
      participants managed for COPD, 130 (53.1%) met the spirometry-based definition
      (post-bronchodilator FEV1/FVC < 0.7) or had a clinical correlation; in 37% of
      cases COPD was not confirmed, and no definitive result was obtained for 9.8% of
      patients. Case finding and subsequent spirometry testing identified 142 new COPD
      cases (17.6% of participants without prior diagnosis; 95% CI, 15.1-20.5%). 690
      participants (65.7%) were current smokers, of whom 360 had attempted quitting
      during the previous 12 months; 286 (81.0% of those attempting to quit) reported
      difficulties during previous quit attempts. Nicotine replacement therapy (205,
      57.4%) and varenicline (110, 30.8%) were the most frequently employed
      pharmacological treatments; side effects were common. Hypnotherapy was the most
      popular non-pharmacological option (62 smokers, 17%); e-cigarettes were tried by
      38 (11%). 187 current smokers (27.6%) would consider using e-cigarettes in future
      attempts to quit. CONCLUSIONS: COPD was both misdiagnosed and missed. Case
      finding and effective use of spirometry testing could improve diagnosis. Side
      effects of smoking cessation medications and difficulties during attempts to quit
      smoking are common. Health professionals should emphasise evidence-based
      treatments, and closely monitor quitting difficulties and side effects of
      cessation aids. TRIAL REGISTRATION: Australian New Zealand Clinical Trials
      Registry ACTRN12614001155684.

PMID- 29320671
TI  - Cognitive impairment during pregnancy: a meta-analysis.
AB  - OBJECTIVES: Many women report declines in cognitive function during pregnancy,
      but attempts to empirically evaluate such changes have yielded inconsistent
      results. We aimed to determine whether pregnancy is associated with objective
      declines in cognitive functioning, and to assess the progression of any declines
      during pregnancy. STUDY DESIGN: We undertook a meta-analysis, applying a random
      effects model, of 20 studies that have reported quantitative relationships
      between pregnancy and changes in cognition. DATA SOURCES: Full text articles
      indexed by Cumulative Index to Nursing and Allied Health Literature (CINAHL)
      Complete, MEDLINE Complete, and PsychINFO. DATA SYNTHESIS: The 20 studies
      assessed included 709 pregnant women and 521 non-pregnant women. Overall
      cognitive functioning was poorer in pregnant women than in non-pregnant women
      (standardised mean difference [SMD], 0.52 [95% CI, 0.07-0.97]; P = 0.025).
      Analysis of cross-sectional studies found that general cognitive functioning
      (SMD, 1.28 [95% CI 0.26-2.30]; P = 0.014), memory (SMD, 1.47 [95% CI, 0.27-2.68];
      P = 0.017), and executive functioning (SMD, 0.46 [95% CI, 0.03-0.89]; P = 0.036)
      were significantly reduced during the third trimester of pregnancy (compared with
      control women), but not during the first two trimesters. Longitudinal studies
      found declines between the first and second trimesters in general cognitive
      functioning (SMD, 0.29 [95% CI, 0.08-0.50]; P = 0.006) and memory (SMD, 0.33 [95%
      CI, 0.12-0.54]; P = 0.002), but not between the second and third trimesters.
      CONCLUSIONS: General cognitive functioning, memory, and executive functioning
      were significantly poorer in pregnant than in control women, particularly during
      the third trimester. The differences primarily develop during the first
      trimester, and are consistent with recent findings of long term reductions in
      brain grey matter volume during pregnancy. The impact of these effects on the
      quality of life and everyday functioning of pregnant women requires further
      investigation.

PMID- 29320672
TI  - Position statement: a clinical approach to the management of adult non-neurogenic
      overactive bladder.
AB  - INTRODUCTION: Overactive bladder (OAB) is a highly prevalent medical condition
      that has an adverse impact on various health-related quality-of-life domains,
      including a significant psychosocial and financial burden. This position
      statement, formulated by members of the Urological Society of Australia and New
      Zealand and the UroGynaecological Society of Australasia, summarises the current
      recommendations for clinical diagnosis and treatment strategies in patients with
      non-neurogenic OAB, and guides clinicians in the decision-making process for
      managing the condition using evidence-based medicine. Main recommendations:
      Diagnosis and initial management should be based on thorough clinical history,
      examination and basic investigations to exclude underlying treatable causes such
      as urinary tract infection and urological malignancy. Initial treatment
      strategies for OAB involve conservative management with behavioural modification
      and bladder retraining. Second-line management involves medical therapy using
      anticholinergic or beta3 agonist drugs provided there is adequate assessment of
      bladder emptying. If medical therapy is unsuccessful, further investigations with
      urodynamic studies and cystourethroscopy are recommended to guide further
      treatment. Intravesical botulinum toxin and sacral neuromodulation should be
      considered in medical refractory OAB. Changes in management as a result of this
      statement: OAB is a constellation of urinary symptoms and is a chronic condition
      with a low likelihood of cure; managing patient expectations is essential because
      OAB is challenging to treat. At present, the exact pathogenesis of OAB remains
      unclear and it is likely that there are multiple factors involved in this disease
      complex. Current medical treatment remains far from ideal, although minimally
      invasive surgery can be effective. Further research into the pathophysiology of
      this common condition will hopefully guide future developments in disease
      management.

PMID- 29320673
TI  - Caution with the forthcoming rescheduling of over-the-counter codeine-containing
      analgesics.

PMID- 29320675
TI  - Leaning in to life.

PMID- 29320674
TI  - No smoker left behind: it's time to tackle tobacco in Australian priority
      populations.

PMID- 29320677
TI  - Warhammers for Peaceful Times.
AB  - The Perkins group has recently developed a number of improved atomic force
      microscopy cantilevers using the focused ion beam technology. They compared the
      performance of these cantilevers in "real-life" biophysical single-molecule force
      spectroscopy measurements on protein unfolding, and the results of this
      comparison are reported in this issue of Biophysical Journal.

PMID- 29320678
TI  - Effect of Ceramide Tail Length on the Structure of Model Stratum Corneum Lipid
      Bilayers.
AB  - Lipid bilayers composed of non-hydroxy sphingosine ceramide (CER NS), cholesterol
      (CHOL), and free fatty acids (FFAs), which are components of the human skin
      barrier, are studied via molecular dynamics simulations. Since mixtures of these
      lipids exist in dense gel phases with little molecular mobility at physiological
      conditions, care must be taken to ensure that the simulations become decorrelated
      from the initial conditions. Thus, we propose and validate an equilibration
      protocol based on simulated tempering, in which the simulation takes a random
      walk through temperature space, allowing the system to break out of metastable
      configurations and hence become decorrelated from its initial configuration.
      After validating the equilibration protocol, which we refer to as random-walk
      molecular dynamics, the effects of the lipid composition and ceramide tail length
      on bilayer properties are studied. Systems containing pure CER NS, CER NS + CHOL,
      and CER NS + CHOL + FFA, with the CER NS fatty acid tail length varied within
      each CER NS-CHOL-FFA composition, are simulated. The bilayer thickness is found
      to depend on the structure of the center of the bilayer, which arises as a result
      of the tail-length asymmetry between the lipids studied. The hydrogen bonding
      between the lipid headgroups and with water is found to change with the overall
      lipid composition, but is mostly independent of the CER fatty acid tail length.
      Subtle differences in the lateral packing of the lipid tails are also found as a
      function of CER tail length. Overall, these results provide insight into the
      experimentally observed trend of altered barrier properties in skin systems where
      there are more CERs with shorter tails present.

PMID- 29320679
TI  - Effect of H-Bond Donor Lipids on Phosphatidylinositol-3,4,5-Trisphosphate
      Ionization and Clustering.
AB  - The phosphoinositide, phosphatidylinositol-3,4,5-trisphosphate (PI(3,4,5)P3), is
      a key signaling lipid in the inner leaflet of the cell plasma membrane,
      regulating diverse signaling pathways including cell growth and migration. In
      this study we investigate the impact of the hydrogen-bond donor lipids
      phosphatidylethanolamine (PE) and phosphatidylinositol (PI) on the charge and
      phase behavior of PI(3,4,5)P3. PE and PI can interact with PI(3,4,5)P3 through
      hydrogen-bond formation, leading to altered ionization behavior and charge
      distribution within the PI(3,4,5)P3 headgroup. We quantify the altered
      PI(3,4,5)P3 ionization behavior using a multistate ionization model to obtain
      micro-pKa values for the ionization of each phosphate group. The presence of PE
      leads to a decrease in the pKa values for the initial deprotonation of
      PI(3,4,5)P3, which describes the removal of the first proton of the three protons
      remaining at the phosphomonoester groups at pH 4.0. The decrease in these micro
      pKa values thus leads to a higher charge at low pH. Additionally, the charge
      distribution changes lead to increased charge on the 3- and 5-phosphates. In the
      presence of PI, the final deprotonation of PI(3,4,5)P3 is delayed, leading to a
      lower charge at high pH. This is due to a combination of hydrogen-bond formation
      between PI and PI(3,4,5)P3, and increased surface charge due to the addition of
      the negatively charged PI. The interaction between PI and PI(3,4,5)P3 leads to
      the formation of PI and PI(3,4,5)P3-enriched domains within the membrane. These
      domains may have a critical impact on PI(3,4,5)P3-signaling. We also reevaluate
      results for all phosphatidylinositol bisphosphates as well as for PI(4,5)P2 in
      complex lipid mixtures with the multistate ionization model.

PMID- 29320680
TI  - K-Ras4B Remains Monomeric on Membranes over a Wide Range of Surface Densities and
      Lipid Compositions.
AB  - Ras is a membrane-anchored signaling protein that serves as a hub for many
      signaling pathways and also plays a prominent role in cancer. The intrinsic
      behavior of Ras on the membrane has captivated the biophysics community in recent
      years, especially the possibility that it may form dimers. In this article, we
      describe results from a comprehensive series of experiments using fluorescence
      correlation spectroscopy and single-molecule tracking to probe the possible
      dimerization of natively expressed and fully processed K-Ras4B in supported lipid
      bilayer membranes. Key to these studies is the fact that K-Ras4B has its native
      membrane anchor, including both the farnesylation and methylation of the terminal
      cysteine, enabling detailed exploration of possible effects of cholesterol and
      lipid composition on K-Ras4B membrane organization. The results from all
      conditions studied indicate that full-length K-Ras4B lacks intrinsic dimerization
      capability. This suggests that any lateral organization of Ras in living cell
      membranes likely stems from interactions with other factors.

PMID- 29320682
TI  - Translational Entropy and DNA Duplex Stability.
AB  - Investigation of folding/unfolding DNA duplexes of various size and composition
      by superprecise calorimetry has revised several long-held beliefs concerning the
      forces responsible for the formation of the double helix. It was established
      that: 1) the enthalpy and the entropy of duplex unfolding are temperature
      dependent, increasing with temperature rise and having the same heat capacity
      increment for CG and AT pairs; 2) the enthalpy of AT melting is greater than that
      of the CG pair, so the stabilizing effect of the CG pair in comparison with AT
      results not from its larger enthalpic contribution (as expected from its extra
      hydrogen bond), but from the larger entropic contribution of the AT pair that
      results from its ability to fix ordered water in the minor groove and release it
      upon duplex unfolding; 3) the translation entropy, resulting from the appearance
      of a new kinetic unit on duplex dissociation, determines the dependence of duplex
      stability on its length and its concentration (it is an order-of-magnitude
      smaller than predicted from the statistical mechanics of gases and is fully
      expressed by the stoichiometric correction term); 4) changes in duplex stability
      on reshuffling the sequence (the "nearest-neighbor effect") result from the
      immobilized water molecules fixed by AT pairs in the minor groove; and 5) the
      evaluated thermodynamic components permit a quantitative expression of DNA duplex
      stability.

PMID- 29320681
TI  - Intrinsic Curvature-Mediated Transbilayer Coupling in Asymmetric Lipid Vesicles.
AB  - We measured the effect of intrinsic lipid curvature, J0, on structural properties
      of asymmetric vesicles made of palmitoyl-oleoyl-phosphatidylethanolamine (POPE;
      J0<0) and palmitoyl-oleoyl-phosphatidylcholine (POPC; J0~0). Electron microscopy
      and dynamic light scattering were used to determine vesicle size and morphology,
      and x-ray and neutron scattering, combined with calorimetric experiments and
      solution NMR, yielded insights into leaflet-specific lipid packing and melting
      processes. Below the lipid melting temperature we observed strong interleaflet
      coupling in asymmetric vesicles with POPE inner bilayer leaflets and outer
      leaflets enriched in POPC. This lipid arrangement manifested itself by lipids
      melting cooperatively in both leaflets, and a rearrangement of lipid packing in
      both monolayers. On the other hand, no coupling was observed in vesicles with
      POPC inner bilayer leaflets and outer leaflets enriched in POPE. In this case,
      the leaflets melted independently and did not affect each other's acyl chain
      packing. Furthermore, we found no evidence for transbilayer structural coupling
      above the melting temperature of either sample preparation. Our results are
      consistent with the energetically preferred location of POPE residing in the
      inner leaflet, where it also resides in natural membranes, most likely causing
      the coupling of both leaflets. The loss of this coupling in the fluid bilayers is
      most likely the result of entropic contributions.

PMID- 29320683
TI  - Changes in Cholesterol Level Alter Integrin Sequestration in Raft-Mimicking Lipid
      Mixtures.
AB  - The influence of cholesterol (CHOL) level on integrin sequestration in raft
      mimicking lipid mixtures forming coexisting liquid-ordered (lo) and liquid
      disordered (ld) lipid domains is investigated using complementary, single
      molecule-sensitive, confocal detection methods. Systematic analysis of membrane
      protein distribution in such a model membrane environment demonstrates that
      variation of CHOL level has a profound influence on lo-ld sequestration of
      integrins, thereby exhibiting overall ld preference in the absence of ligands and
      lo affinity upon vitronectin addition. Accompanying photon-counting histogram
      analysis of integrins in the different model membrane mixtures shows that the
      observed changes of integrin sequestration in response to variations of membrane
      CHOL level are not associated with altering integrin oligomerization states.
      Instead, our experiments suggest that the strong CHOL dependence of integrin
      sequestration can be attributed to CHOL-mediated changes of lipid packing and
      bilayer thickness in coexisting lo and ld domains, highlighting the significance
      of a biophysical mechanism of CHOL-mediated regulation of integrin sequestration.
      We envision that this model membrane study may help clarify the influence of CHOL
      in integrin functionality in plasma membranes, thus providing further insight
      into the role of lipid heterogeneities in membrane protein distribution and
      function in a cellular membrane environment.

PMID- 29320684
TI  - Label-free Imaging and Bending Analysis of Microtubules by ROCS Microscopy and
      Optical Trapping.
AB  - Mechanical manipulation of single cytoskeleton filaments and their monitoring
      over long times is difficult because of fluorescence bleaching or phototoxic
      protein degradation. The integration of label-free microscopy techniques, capable
      of imaging freely diffusing, weak scatterers such as microtubules (MTs) in real
      time, and independent of their orientation, with optical trapping and tracking
      systems, would allow many new applications. Here, we show that rotating-coherent
      scattering microscopy (ROCS) in dark-field mode can also provide strong contrast
      for structures far from the coverslip such as arrangements of isolated MTs and
      networks. We could acquire thousands of images over up to 30 min without loss in
      image contrast or visible photodamage. We further demonstrate the combination of
      ROCS imaging with fast and nanometer-precise 3D interferometric back-focal-plane
      tracking of multiple beads in time-shared optical traps using acoustooptic
      deflectors to specifically construct and microrheologically probe small
      microtubule networks with well-defined geometries. Thereby, we explore the
      frequency-dependent elastic response of single microtubule filaments between 0.5
      Hz and 5 kHz, which allows for investigating their viscoelastic response up to
      the fourth-order bending mode. Our spectral analysis reveals constant filament
      stiffness at low frequencies and frequency-dependent stiffening following a power
      law ~omegap with a length-dependent exponent p(L). We find further evidence for
      the dependence of the MT persistence length on the contour length L, which is
      still controversially debated. We could also demonstrate slower stiffening at
      high frequencies for longer filaments, which we believe is determined by the
      molecular architecture of the MT. Our results shed new light on the nanomechanics
      of this essential, multifunctional cytoskeletal element and pose new questions
      about the adaptability of the cytoskeleton.

PMID- 29320685
TI  - Essential Role of the epsilon Subunit for Reversible Chemo-Mechanical Coupling in
      F1-ATPase.
AB  - F1-ATPase is a rotary motor protein driven by ATP hydrolysis. Among molecular
      motors, F1 exhibits unique high reversibility in chemo-mechanical coupling,
      synthesizing ATP from ADP and inorganic phosphate upon forcible rotor reversal.
      The epsilon subunit enhances ATP synthesis coupling efficiency to > 70% upon
      rotation reversal. However, the detailed mechanism has remained elusive. In this
      study, we performed stall-and-release experiments to elucidate how the epsilon
      subunit modulates ATP association/dissociation and hydrolysis/synthesis process
      kinetics and thermodynamics, key reaction steps for efficient ATP synthesis. The
      epsilon subunit significantly accelerated the rates of ATP dissociation and
      synthesis by two- to fivefold, whereas those of ATP binding and hydrolysis were
      not enhanced. Numerical analysis based on the determined kinetic parameters
      quantitatively reproduced previous findings of two- to fivefold coupling
      efficiency improvement by the epsilon subunit at the condition exhibiting the
      maximum ATP synthesis activity, a physiological role of F1-ATPase. Furthermore,
      fundamentally similar results were obtained upon epsilon subunit C-terminal
      domain truncation, suggesting that the N-terminal domain is responsible for the
      rate enhancement.

PMID- 29320686
TI  - Dynamic Model for Characterizing Contractile Behaviors and Mechanical Properties
      of a Cardiomyocyte.
AB  - Studies on the contractile dynamics of heart cells have attracted broad attention
      for the development of both heart disease therapies and cardiomyocyte-actuated
      micro-robotics. In this study, a linear dynamic model of a single cardiomyocyte
      cell was proposed at the subcellular scale to characterize the contractile
      behaviors of heart cells, with system parameters representing the mechanical
      properties of the subcellular components of living cardiomyocytes. The system
      parameters of the dynamic model were identified with the cellular beating pattern
      measured by a scanning ion conductance microscope. The experiments were
      implemented with cardiomyocytes in one control group and two experimental groups
      with the drugs cytochalasin-D or nocodazole, to identify the system parameters of
      the model based on scanning ion conductance microscope measurements, measurement
      of the cellular Young's modulus with atomic force microscopy indentation,
      measurement of cellular contraction forces using the micro-pillar technique, and
      immunofluorescence staining and imaging of the cytoskeleton. The proposed
      mathematical model was both indirectly and qualitatively verified by the
      variation in cytoskeleton, beating amplitude, and contractility of cardiomyocytes
      among the control and the experimental groups, as well as directly and
      quantitatively validated by the simulation and the significant consistency of
      90.5% in the comparison between the ratios of the Young's modulus and the
      equivalent comprehensive cellular elasticities of cells in the experimental
      groups to those in the control group. Apart from mechanical properties (mass,
      elasticity, and viscosity) of subcellular structures, other properties of
      cardiomyocytes have also been studied, such as the properties of the relative
      action potential pattern and cellular beating frequency. This work has potential
      implications for research on cytobiology, drug screening, mechanisms of the
      heart, and cardiomyocyte-based bio-syncretic robotics.

PMID- 29320687
TI  - Microtubule Polymerization and Cross-Link Dynamics Explain Axonal Stiffness and
      Damage.
AB  - Axonal damage is a critical indicator for traumatic effects of physical impact to
      the brain. However, the precise mechanisms of axonal damage are still unclear.
      Here, we establish a mechanistic and highly dynamic model of the axon to explore
      the evolution of damage in response to physical forces. Our axon model consists
      of a bundle of dynamically polymerizing and depolymerizing microtubules connected
      by dynamically detaching and reattaching cross-links. Although the probability of
      cross-link attachment depends exclusively on thermal fluctuations, the
      probability of detachment increases in the presence of physical forces. We
      systematically probe the landscape of axonal stretch and stretch rate and
      characterize the overall axonal force, stiffness, and damage as a direct result
      of the interplay between microtubule and cross-link dynamics. Our simulations
      reveal that slow loading is dominated by cross-link dynamics, a net reduction of
      cross-links, and a gradual accumulation of damage, whereas fast loading is
      dominated by cross-link deformations, a rapid increase in stretch, and an
      immediate risk of rupture. Microtubule polymerization and depolymerization
      decrease the overall axonal stiffness, but do not affect the evolution of damage
      at timescales relevant to axonal failure. Our study explains different failure
      mechanisms in the axon as emergent properties of microtubule polymerization,
      cross-link dynamics, and physical forces. We anticipate that our model will
      provide insight into causal relations by which molecular mechanisms determine the
      timeline and severity of axon damage after a physical impact to the brain.

PMID- 29320688
TI  - Coevolutionary Landscape of Kinase Family Proteins: Sequence Probabilities and
      Functional Motifs.
AB  - The protein kinase catalytic domain is one of the most abundant domains across
      all branches of life. Although kinases share a common core function of phosphoryl
      transfer, they also have wide functional diversity and play varied roles in cell
      signaling networks, and for this reason are implicated in a number of human
      diseases. This functional diversity is primarily achieved through sequence
      variation, and uncovering the sequence-function relationships for the kinase
      family is a major challenge. In this study we use a statistical inference
      technique inspired by statistical physics, which builds a coevolutionary "Potts"
      Hamiltonian model of sequence variation in a protein family. We show how this
      model has sufficient power to predict the probability of specific subsequences in
      the highly diverged kinase family, which we verify by comparing the model's
      predictions with experimental observations in the Uniprot database. We show that
      the pairwise (residue-residue) interaction terms of the statistical model are
      necessary and sufficient to capture higher-than-pairwise mutation patterns of
      natural kinase sequences. We observe that previously identified functional sets
      of residues have much stronger correlated interaction scores than are typical.

PMID- 29320689
TI  - Collective Cell Migration in Embryogenesis Follows the Laws of Wetting.
AB  - Collective cell migration is a fundamental process during embryogenesis and its
      initial occurrence, called epiboly, is an excellent in vivo model to study the
      physical processes involved in collective cell movements that are key to
      understanding organ formation, cancer invasion, and wound healing. In zebrafish,
      epiboly starts with a cluster of cells at one pole of the spherical embryo. These
      cells are actively spreading in a continuous movement toward its other pole until
      they fully cover the yolk. Inspired by the physics of wetting, we determine the
      contact angle between the cells and the yolk during epiboly. By choosing a
      wetting approach, the relevant scale for this investigation is the tissue level,
      which is in contrast to other recent work. Similar to the case of a liquid drop
      on a surface, one observes three interfaces that carry mechanical tension.
      Assuming that interfacial force balance holds during the quasi-static spreading
      process, we employ the physics of wetting to predict the temporal change of the
      contact angle. Although the experimental values vary dramatically, the model
      allows us to rescale all measured contact-angle dynamics onto a single master
      curve explaining the collective cell movement. Thus, we describe the fundamental
      and complex developmental mechanism at the onset of embryogenesis by only three
      main parameters: the offset tension strength, alpha, that gives the strength of
      interfacial tension compared to other force-generating mechanisms; the tension
      ratio, delta, between the different interfaces; and the rate of tension
      variation, lambda, which determines the timescale of the whole process.

PMID- 29320690
TI  - Sharing of Phosphatases Promotes Response Plasticity in Phosphorylation Cascades.
AB  - Sharing of positive or negative regulators between multiple targets is frequently
      observed in cellular signaling cascades. For instance, phosphatase sharing
      between multiple kinases is ubiquitous within the MAPK pathway. Here we
      investigate how such phosphatase sharing could shape robustness and evolvability
      of the phosphorylation cascade. Through modeling and evolutionary simulations, we
      demonstrate that 1) phosphatase sharing dramatically increases robustness of a
      bistable MAPK response, and 2) phosphatase-sharing cascades evolve faster than
      nonsharing cascades. This faster evolution is particularly pronounced when
      evolving from a monostable toward a bistable phenotype, whereas the transition
      speed of a population from a bistable to monostable response is not affected by
      phosphatase sharing. This property may enable the phosphatase-sharing design to
      adapt better in a changing environment. Analysis of the respective mutational
      landscapes reveal that phosphatase sharing reduces the number of limiting
      mutations required for transition from monostable to bistable responses, hence
      facilitating a faster transition to such response types. Taken together, using
      MAPK cascade as an example, our study offers a general theoretical framework to
      explore robustness and evolutionary plasticity of signal transduction cascades.

PMID- 29320692
TI  - Signaling Architectures that Transmit Unidirectional Information Despite
      Retroactivity.

PMID- 29320691
TI  - Network Features and Dynamical Landscape of Naive and Primed Pluripotency.
AB  - Although the broad and unique differentiation potential of pluripotent stem cells
      relies on a complex transcriptional network centered around Oct4, Sox2, and
      Nanog, two well-distinct pluripotent states, called "naive" and "primed", have
      been described in vitro and markedly differ in their developmental potential,
      their expression profiles, their signaling requirements, and their reciprocal
      conversion. Aiming to determine the key features that segregate and coordinate
      these two states, data-driven optimization of network models is performed to
      identify relevant parameter regimes and reduce network complexity to its core
      structure. Decision dynamics of optimized networks is characterized by signal
      dependent multistability and strongly asymmetric transitions among naive, primed,
      and nonpluripotent states. Further model perturbation and reduction approaches
      reveal that such a dynamical landscape of pluripotency involves a functional
      partitioning of the regulatory network. Specifically, two overlapping positive
      feedback modules, Klf4/Esrrb/Nanog and Oct4/Nanog, stabilize the naive or the
      primed state, respectively. In turn, their incoherent feedforward and negative
      feedback coupling mediated by the Erk/Gsk3 module is critical for robust
      segregation and sequential progression between naive and primed states before
      irreversible exit from pluripotency.

PMID- 29320693
TI  - Mechanical Transduction and the Dark Energy of Biology.

PMID- 29320694
TI  - Dynamic Structural Differences between Human and Mouse STING Lead to Differing
      Sensitivity to DMXAA.
AB  - The stimulator-of-interferon-genes (STING) protein is involved in innate
      immunity. It has recently been shown that modulation of STING can lead to an
      aggressive antitumor response. DMXAA is an antitumor agent that had shown great
      promise in murine models but failed in human clinical trials. The molecular
      target of DMXAA was subsequently shown to be murine STING (mSTING); however,
      human STING (hSTING) is insensitive to DMXAA. Molecular dynamics simulations were
      employed to investigate the differences between hSTING and mSTING that could
      influence DMXAA binding. An initial set of simulations was performed to
      investigate a single lid region mutation G230I in hSTING (corresponding residue
      in mSTING is an Ile), which rendered the protein sensitive to DMXAA. The
      simulations found that an Ile side chain was enough to form a steric barrier that
      prevents exit of DMXAA, whereas in WT hSTING, the Gly residue that lacks a side
      chain formed a porous lid region that allowed DMXAA to exit. A second set of
      molecular dynamics simulations compared the tendency of STING to be in an open
      inactive conformation or a closed-active conformation. The results show that
      hSTING prefers to be in an open-inactive conformation even with cGAMP, the native
      ligand, bound. On the other hand, mSTING prefers a closed-active conformation
      even without a ligand bound. These results highlight the challenges in
      translating a mouse active STING compound into a human active compound, while
      also providing avenues to pursue for designing a small-molecule drug targeting
      human STING.

PMID- 29320695
TI  - Decrypting the Heat Activation Mechanism of TRPV1 Channel by Molecular Dynamics
      Simulation.
AB  - As a prototype cellular sensor, the TRPV1 cation channel undergoes a closed-to
      open gating transition in response to various physical and chemical stimuli
      including noxious heat. Despite recent progress, the molecular mechanism of heat
      activation of TRPV1 gating remains enigmatic. Toward decrypting the structural
      basis of TRPV1 heat activation, we performed extensive molecular dynamics
      simulations (with cumulative simulation time of ~11 MUs) for the wild-type
      channel and a constitutively active double mutant at different temperatures (30,
      60, and 72 degrees C), starting from a high-resolution closed-channel structure
      of TRPV1 solved by cryo-electron microscopy. In the wild-type simulations, we
      observed heat-activated conformational changes (e.g., expansion or contraction)
      in various key domains of TRPV1 (e.g., the S2-S3 and S4-S5 linkers) to prime the
      channel for gating. These conformational changes involve a number of dynamic
      hydrogen-bond interactions that were validated with previous mutational studies.
      Next, our mutant simulations observed channel opening after a series of
      conformational changes that propagate from the channel periphery to the channel
      pore via key intermediate domains (including the S2-S3 and S4-S5 linkers). The
      gating transition is accompanied by a large increase in the protein-water
      electrostatic interaction energy, which supports the contribution of desolvation
      of polar/charged residues to the temperature-sensitive TRPV1 gating. Taken
      together, our molecular dynamics simulations and analyses offered, to our
      knowledge, new structural, dynamic, and energetic information to guide future
      mutagenesis and functional studies of the TRPV1 channels and development of TRPV1
      targeting drugs.

PMID- 29320696
TI  - Using a FRET Library with Multiple Probe Pairs To Drive Monte Carlo Simulations
      of alpha-Synuclein.
AB  - We describe a strategy for experimentally-constraining computational simulations
      of intrinsically disordered proteins (IDPs), using alpha-synuclein, an IDP with a
      central role in Parkinson's disease pathology, as an example. Previously, data
      from single-molecule Forster Resonance Energy Transfer (FRET) experiments have
      been effectively utilized to generate experimentally constrained computational
      models of IDPs. However, the fluorophores required for single-molecule FRET
      experiments are not amenable to the study of short-range (<30 A) interactions.
      Using ensemble FRET measurements allows one to acquire data from probes with
      multiple distance ranges, which can be used to constrain Monte Carlo simulations
      in PyRosetta. To appropriately employ ensemble FRET data as constraints, we
      optimized the shape and weight of constraining potentials to afford ensembles of
      structures that are consistent with experimental data. We also used this approach
      to examine the structure of alpha-synuclein in the presence of the compacting
      osmolyte trimethylamine-N-oxide. Despite significant compaction imparted by 2 M
      trimethylamine-N-oxide, the underlying ensemble of alpha-synuclein remains
      largely disordered and capable of aggregation, also in agreement with
      experimental data. These proof-of-concept experiments demonstrate that our
      modeling protocol enables one to efficiently generate experimentally constrained
      models of IDPs that incorporate atomic-scale detail, allowing one to study an IDP
      under a variety of conditions.

PMID- 29320697
TI  - Effects of pH and Salt Concentration on Stability of a Protein G Variant Using
      Coarse-Grained Models.
AB  - The importance of charge-charge interactions in the thermal stability of proteins
      is widely known. pH and ionic strength play a crucial role in these electrostatic
      interactions, as well as in the arrangement of ionizable residues in each protein
      folding stage. In this study, two coarse-grained models were used to evaluate the
      effect of pH and salt concentration on the thermal stability of a protein G
      variant (1PGB-QDD), which was chosen due to the quantity of experimental data
      exploring these effects on its stability. One of these coarse-grained models, the
      TKSA, calculates the electrostatic free energy of the protein in the native state
      via the Tanford-Kirkwood approach for each residue. The other one, CpHMD-SBM,
      uses a Coulomb screening potential in addition to the structure-based model
      Calpha. Both models simulate the system in constant pH. The comparison between
      the experimental stability analysis and the computational results obtained by
      these simple models showed a good agreement. Through the TKSA method, the role of
      each charged residue in the protein's thermal stability was inferred. Using CpHMD
      SBM, it was possible to evaluate salt and pH effects throughout the folding
      process. Finally, the computational pKa values were calculated by both methods
      and presented a good level of agreement with the experiments. This study
      provides, to our knowledge, new information and a comprehensive description of
      the electrostatic contribution to protein G stability.

PMID- 29320698
TI  - Ion Specificity and Nonmonotonic Protein Solubility from Salt Entropy.
AB  - The addition of salt to protein solutions can either increase or decrease the
      protein solubility, and the magnitude of this effect depends on the salt used. We
      show that these effects can be captured using a theory that includes attractive
      and repulsive electrostatic interactions, nonelectrostatic protein-ion
      interactions, and ion-solvent interactions via an effective solvated ion radius.
      We find that the ion radius has significant effects on the translational entropy
      of the salt, which leads to salt specificity in the protein solubility. At low
      salt, the dominant effect comes from the entropic cost of confining ions within
      the aggregate, whereas at high concentrations, the salt drives a depletion
      attraction that favors aggregation. Our theory explains the reversal in the
      Hofmeister series observed in lysozyme cloud point measurements and semi
      quantitatively describes the solubility of lysozyme and chymosin crystals. We
      present a comparison of the contributions to the free energy and give guidelines
      for when salting in or salting out should be expected.

PMID- 29320699
TI  - LRET Determination of Molecular Distances during pH Gating of the Mammalian
      Inward Rectifier Kir1.1b.
AB  - Gating of the mammalian inward rectifier Kir1.1 at the helix bundle crossing
      (HBC) by intracellular pH is believed to be mediated by conformational changes in
      the C-terminal domain (CTD). However, the exact motion of the CTD during Kir
      gating remains controversial. Crystal structures and single-molecule fluorescence
      resonance energy transfer of KirBac channels have implied a rigid body rotation
      and/or a contraction of the CTD as possible triggers for opening of the HBC gate.
      In our study, we used lanthanide-based resonance energy transfer on single-Cys
      dimeric constructs of the mammalian renal inward rectifier, Kir1.1b, incorporated
      into anionic liposomes plus PIP2, to determine unambiguous, state-dependent
      distances between paired Cys residues on diagonally opposite subunits.
      Functionality and pH dependence of our proteoliposome channels were verified in
      separate electrophysiological experiments. The lanthanide-based resonance energy
      transfer distances measured in closed (pH 6) and open (pH 8) conditions indicated
      neither expansion nor contraction of the CTD during gating, whereas the HBC gate
      widened by 8.8 +/- 4 A, from 6.3 +/- 2 to 15.1 +/- 6 A, during opening. These
      results are consistent with a Kir gating model in which rigid body rotation of
      the large CTD around the permeation axis is correlated with opening of the HBC
      hydrophobic gate, allowing permeation of a 7 A hydrated K ion.

PMID- 29320701
TI  - Aminoacylation of Proteins: New Targets for the Old ARSenal.
AB  - Besides charging tRNAs with their cognate amino acids, aminoacyl-tRNA synthetases
      (ARSs) are involved in a plethora of non-canonical functions, including
      development, immune response, and angiogenesis. In this issue of Cell Metabolism,
      He et al. (2018) report a novel biochemical function of ARSs: posttranslational
      addition of amino acids to lysine residues in proteins.

PMID- 29320700
TI  - Role of Phosphorylation in Moesin Interactions with PIP2-Containing Biomimetic
      Membranes.
AB  - Moesin, a protein of the ezrin, radixin, and moesin family, which links the
      plasma membrane to the cytoskeleton, is involved in multiple physiological and
      pathological processes, including viral budding and infection. Its interaction
      with the plasma membrane occurs via a key phosphoinositide, the
      phosphatidyl(4,5)inositol-bisphosphate (PIP2), and phosphorylation of residue
      T558, which has been shown to contribute, in cellulo, to a conformationally open
      protein. We study the impact of a double phosphomimetic mutation of moesin
      (T235D, T558D), which mimics the phosphorylation state of the protein, on
      protein/PIP2/microtubule interactions. Analytical ultracentrifugation in the
      micromolar range showed moesin in the monomer and dimer forms, with wild-type
      (WT) moesin containing a slightly larger fraction (~30%) of dimers than DD moesin
      (10-20%). Only DD moesin was responsive to PIP2 in its micellar form.
      Quantitative cosedimentation assays using large unilamellar vesicles and quartz
      crystal microbalance on supported lipid bilayers containing PIP2 reveal a
      specific cooperative interaction for DD moesin with an ability to bind two PIP2
      molecules simultaneously, whereas WT moesin was able to bind only one. In
      addition, DD moesin could subsequently interact with microtubules, whereas WT
      moesin was unable to do so. Altogether, our results point to an important role of
      these two phosphorylation sites in the opening of moesin: since DD moesin is
      intrinsically in a more open conformation than WT moesin, this intermolecular
      interaction is reinforced by its binding to PIP2. We also highlight important
      differences between moesin and ezrin, which appear to be finely regulated and to
      exhibit distinct molecular behaviors.

PMID- 29320703
TI  - Three-Dimensional Adipose Tissue Imaging Reveals Regional Variation in Beige Fat
      Biogenesis and PRDM16-Dependent Sympathetic Neurite Density.
AB  - While the cell-intrinsic pathways governing beige adipocyte development and
      phenotype have been increasingly delineated, comparatively little is known about
      how beige adipocytes interact with other cell types in fat. Here, we introduce a
      whole-tissue clearing method for adipose that permits immunolabeling and three
      dimensional profiling of structures including thermogenic adipocytes and
      sympathetic innervation. We found that tissue architecture and sympathetic
      innervation differ significantly between subcutaneous and visceral depots.
      Subcutaneous fat demonstrates prominent regional variation in beige fat
      biogenesis with localization of UCP1+ beige adipocytes to areas with dense
      sympathetic neurites. We present evidence that the density of sympathetic
      projections is dependent on PRDM16 in adipocytes, providing another potential
      mechanism underlying the metabolic benefits mediated by PRDM16. This powerful
      imaging tool highlights the interaction of tissue components during beige fat
      biogenesis and reveals a previously undescribed mode of regulation of the
      sympathetic nervous system by adipocytes.

PMID- 29320702
TI  - Repression of Adipose Tissue Fibrosis through a PRDM16-GTF2IRD1 Complex Improves
      Systemic Glucose Homeostasis.
AB  - Adipose tissue fibrosis is a hallmark of malfunction that is linked to insulin
      resistance and type 2 diabetes; however, what regulates this process remains
      unclear. Here we show that the PRDM16 transcriptional complex, a dominant
      activator of brown/beige adipocyte development, potently represses adipose tissue
      fibrosis in an uncoupling protein 1 (UCP1)-independent manner. By purifying the
      PRDM16 complex, we identified GTF2IRD1, a member of the TFII-I family of DNA
      binding proteins, as a cold-inducible transcription factor that mediates the
      repressive action of the PRDM16 complex on fibrosis. Adipocyte-selective
      expression of GTF2IRD1 represses adipose tissue fibrosis and improves systemic
      glucose homeostasis independent of body-weight loss, while deleting GTF2IRD1
      promotes fibrosis in a cell-autonomous manner. GTF2IRD1 represses the
      transcription of transforming growth factor beta-dependent pro-fibrosis genes by
      recruiting PRDM16 and EHMT1 onto their promoter/enhancer regions. These results
      suggest a mechanism by which repression of obesity-associated adipose tissue
      fibrosis through the PRDM16 complex leads to an improvement in systemic glucose
      homeostasis.

PMID- 29320704
TI  - Extracellular Vesicles Provide a Means for Tissue Crosstalk during Exercise.
AB  - Exercise stimulates the release of molecules into the circulation, supporting the
      concept that inter-tissue signaling proteins are important mediators of
      adaptations to exercise. Recognizing that many circulating proteins are packaged
      in extracellular vesicles (EVs), we employed quantitative proteomic techniques to
      characterize the exercise-induced secretion of EV-contained proteins. Following a
      1-hr bout of cycling exercise in healthy humans, we observed an increase in the
      circulation of over 300 proteins, with a notable enrichment of several classes of
      proteins that compose exosomes and small vesicles. Pulse-chase and intravital
      imaging experiments suggested EVs liberated by exercise have a propensity to
      localize in the liver and can transfer their protein cargo. Moreover, by
      employing arteriovenous balance studies across the contracting human limb, we
      identified several novel candidate myokines, released into circulation
      independently of classical secretion. These data identify a new paradigm by which
      tissue crosstalk during exercise can exert systemic biological effects.

PMID- 29320706
TI  - Human CIA2A-FAM96A and CIA2B-FAM96B Integrate Iron Homeostasis and Maturation of
      Different Subsets of Cytosolic-Nuclear Iron-Sulfur Proteins.

PMID- 29320705
TI  - An Adipose Tissue Atlas: An Image-Guided Identification of Human-like BAT and
      Beige Depots in Rodents.
AB  - [18F]Fluorodeoxyglucose-PET/CT (18F-FDG-PET/CT) imaging has been invaluable for
      visualizing metabolically active adipose tissues in humans with potential anti
      diabetic and anti-obesity effects. To explore whether mice display human-like fat
      depots in anatomically comparable regions, we mapped fat depots using glucose or
      fatty acid imaging tracers, such as 18F-FDG through PET/CT or [123/125I]-beta
      methyl-p-iodophenyl-pentadecanoic acid with SPECT/CT imaging, to analogous depots
      in mice. Using this type of image analysis with both probes, we define a large
      number of additional areas of high metabolic activity corresponding to novel fat
      pads. Histological and gene expression analyses validate these regions as bona
      fide fat pads. Our findings indicate that fat depots of rodents show a high
      degree of topological similarity to those of humans. Studies involving both
      glucose and lipid tracers indicate differential preferences for these substrates
      in different depots and also suggest that fatty acid-based visualized approaches
      may reveal additional brown adipose tissue and beige depots in humans.

PMID- 29320707
TI  - SnapShot: Niche Determines Adipocyte Character I.
AB  - Adipose tissues are complex organs, with central roles in energy homeostasis as
      well as local functions. Adipocytes develop in diverse, discrete locations
      throughout the body. Important regional differences in adipocytes exist, and
      diseases that affect adipose tissues often demonstrate depot-specific effects.
      Herein, we depict the widespread locations of major and minor rodent adipose
      depots. Depot-specific molecular and functional characteristics will be described
      in Part II.

PMID- 29320708
TI  - SnapShot: Niche Determines Adipocyte Character II.
AB  - The intrinsic cellular and metabolic properties of an adipocyte are shaped by the
      specific niche in which it resides. The diverse and discrete locations of major
      and minor rodent adipose depots are depicted in Part I. In Part II, the molecular
      and functional characteristics of four major types of adipocytes are described.
      Identified functions of relatively understudied but undoubtedly important depots
      are also highlighted.

PMID- 29320709
TI  - Metabolic Reprogramming via Targeting CD38 NADase Augments Adoptive T Cell
      Therapy.
AB  - One strategy to improve the potency of adoptive T cell therapy is to augment the
      function and persistence of anti-tumor T cells. In this issue of Cell Metabolism,
      Chatterjee et al. (2018) demonstrate that intratumoral CD4+ T cell functions and
      memory can be improved by targeting a CD38-NAD+-Sirt1-Foxo1 metabolic circuit.

PMID- 29320710
TI  - Apoptotic Regulatory T Cells Retain Suppressive Function through Adenosine.
AB  - Regulatory T cells maintain tolerance and prevent autoimmunity, but their
      suppressive effects can hinder immune responses against cancer. In Nature
      Immunology, Maj et al., 2017 report that regulatory T cells can execute these
      actions through the nucleoside adenosine even after cell death.

PMID- 29320712
TI  - SERCA2b Cycles Its Way to UCP1-Independent Thermogenesis in Beige Fat.
AB  - A new study in Nature Medicine, by Ikeda et al. (2017), reports that calcium
      cycling in beige adipocytes elevates energy expenditure and glucose oxidation in
      the absence of uncoupling protein 1. Thermogenic calcium cycling in beige fat is
      mediated by SERCA2b and improves cold tolerance and metabolic status.

PMID- 29320713
TI  - Recurrent ventricular fibrillation associated with acute ingestion of
      hydrofluoric acid.

PMID- 29320714
TI  - A case report of mesenteric heterotopic ossification: Histopathologic and genetic
      findings.
AB  - Mesenteric heterotopic ossification (MHO) is very rare and occurs in mid- to late
      adulthood, usually in the context of prior abdominal surgery. The mechanisms of
      MHO are unknown. Here we describe the case of a 72-year-old man with MHO.
      Standard histological staining revealed that MHO occurred through an endochondral
      process. By comparison to known mutations in genetic conditions of HO such as
      fibrodysplasia ossificans progressiva (FOP) and progressive osseous heteroplasia
      (POH), DNA sequencing analysis demonstrated the presence of a commonly occurring
      heterozygous synonymous polymorphism (c.690G>A; E230E) in the causative gene for
      FOP (ACVR1/ALK2). However, no frameshift, missense, or nonsense mutations in
      ACVR1, or in the causative gene for POH (GNAS), were found. Although genetic
      predisposition may play a role in MHO, our data suggest that mutations which
      occur in known hereditary conditions of HO are not the primary cause.

PMID- 29320715
TI  - Subcortical pathways to extrastriate visual cortex underlie residual vision
      following bilateral damage to V1.
AB  - Residual vision, or blindsight, following damage to the primary visual cortex
      (V1) has been investigated for almost half a century. While there have been many
      studies of patients with unilateral damage to V1, far fewer have examined
      bilateral damage, mainly due to the rarity of such patients. Here we re-examine
      the residual visual function and underlying pathways of previously studied
      patient SBR who, as a young adult, suffered bilateral damage restricted to V1
      which rendered him cortically blind. While earlier work compared his visual
      cortex to healthy, sighted participants, here we consider how his visual
      responses and connections compare to patients with unilateral damage to V1 in
      addition to sighted participants. Detection of drifting Gabor patches of
      different contrasts (1%, 5%, 10%, 50% and 100%) was tested in SBR and a group of
      eight patients with unilateral damage to V1. Performance was compared to the
      neural activation in motion area hMT+ measured using functional magnetic
      resonance imaging. Diffusion tractography was also used to determine the white
      matter microstructure of the visual pathways in all participants. Like the
      patients with unilateral damage, patient SBR showed increased % BOLD signal
      change to the high contrast stimuli that he could detect compared to the lower
      contrast stimuli that were not detectable. Diffusion tractography suggests this
      information is conveyed by a direct pathway between the lateral geniculate
      nucleus (LGN) and hMT+ since this pathway had microstructure that was comparable
      to the healthy control group. In contrast, the pathway between LGN and V1 had
      reduced integrity compared to controls. A further finding of note was that,
      unlike control participants, SBR showed similar patterns of contralateral and
      ipsilateral activity in hMT+, in addition to healthy white matter microstructure
      in the tract connecting hMT+ between the two hemispheres. This raises the
      possibility of increased connectivity between the two hemispheres in the absence
      of V1 input. In conclusion, the pattern of visual function and anatomy in
      bilateral cortical damage is comparable to that seen in a group of patients with
      unilateral damage. Thus, while the intact hemisphere may play a role in residual
      vision in patients with unilateral damage, its influence is not evident with the
      methodology employed here.

PMID- 29320711
TI  - Anatomical, Physiological, and Functional Diversity of Adipose Tissue.
AB  - Adipose tissue depots can exist in close association with other organs, where
      they assume diverse, often non-traditional functions. In stem cell-rich skin,
      bone marrow, and mammary glands, adipocytes signal to and modulate organ
      regeneration and remodeling. Skin adipocytes and their progenitors signal to hair
      follicles, promoting epithelial stem cell quiescence and activation,
      respectively. Hair follicles signal back to adipocyte progenitors, inducing their
      expansion and regeneration, as in skin scars. In mammary glands and heart,
      adipocytes supply lipids to neighboring cells for nutritional and metabolic
      functions, respectively. Adipose depots adjacent to skeletal structures function
      to absorb mechanical shock. Adipose tissue near the surface of skin and intestine
      senses and responds to bacterial invasion, contributing to the body's innate
      immune barrier. As the recognition of diverse adipose depot functions increases,
      novel therapeutic approaches centered on tissue-specific adipocytes are likely to
      emerge for a range of cancers and regenerative, infectious, and autoimmune
      disorders.

PMID- 29320716
TI  - Distinct roles of systemic and local actions of insulin on pancreatic beta-cells.
AB  - OBJECTIVE: Pancreatic beta-cell mass and function are critical in glucose
      homeostasis. Their regulatory mechanisms have been studied principally under
      experimental conditions of reduced beta-cell numbers, such as beta-cell ablation
      and partial pancreatectomy. In the present study, we generated an opposite mouse
      model with an excessive amount of ectopic beta-cells, and analyzed its
      consequence on beta-cell mass and survival. METHODS: Mice underwent sub-renal
      transplantation (SRT) of pseudo-islets generated from a pancreatic beta-cell line
      MIN6 or intra-pancreatic transplantation (IPT) of MIN6 cells, and morphological
      and functional changes of their endocrine pancreata were analyzed. Cellular fate
      of pancreatic beta-cells after transplantation was traced using RipCre:Rosa26
      tdTomato mice. By using MIN6 cells, we evaluated the roles of extracellular
      glucose, membrane potential, and insulin signaling on beta-cell survival.
      RESULTS: SRT mice developed severe, progressive hypoglycemia associated with
      marked reduction in insulin-positive (Ins+) cell mass and apparent increase in
      apoptotic Ins+ cells. In in vitro experiments of MIN6 cells, insulin signaling
      blockade potently induced cell death, suggesting that local insulin action is
      required for beta-cell survival. In fact, IPT (i.e. transplantation close to
      endogenous beta-cells) resulted in fewer apoptotic Ins+ cells compared with those
      induced by SRT. On the other hand, beta-cell mass was decreased in proportion to
      the decrease in blood glucose levels in both SRT and IPT mice, suggesting a
      contribution of hypoglycemia induced by systemic hyperinsulinemia. CONCLUSION:
      Insulin plays distinct roles in beta-cell survival and beta-cell mass regulation
      through its local and systemic actions on beta-cells, respectively.

PMID- 29320717
TI  - Imitation of phase I metabolism reactions of MAO-A inhibitors by titanium dioxide
      photocatalysis.
AB  - The imitation of phase I metabolism of moclobemide and toloxatone, two monoamine
      oxidase type A (MAO-A) inhibitors, was performed with the use of titanium dioxide
      photocatalytic process. Ultra high pressure liquid chromatography system coupled
      with an accurate hybrid ESI-Q-TOF mass spectrometer was used for the evaluation
      of metabolic profiles, structural elucidation of the identified transformation
      products and quantitative analysis of the process. Based on high resolution MS
      and MS/MS data, eleven transformation products were characterized in
      photocatalytic experiments for moclobemide and seven products for toloxatone. A
      significant number of these products were found as hepatic metabolites under the
      incubation of the selected MAO-A inhibitors with human liver microsomes (HLM).
      What is important, some of these HLM metabolites are not yet described in the
      literature. It was also found that the multivariate chemometric analysis allowed
      an effortless characterization of the registered metabolic profiles which can be
      a useful method for a fast preliminary drug metabolism study. Additionally,
      principal component analysis (PCA) of the registered TOF (MS) photocatalytic and
      HLM profiles of moclobemide and toloxatone shows that shorter irradiation time is
      preferred for photocatalytic metabolism experiments. A heterogeneous
      photocatalysis with the use of titanium dioxide was found to be a powerful tool
      for mimicking phase I metabolic reactions, as a fast, sensitive and inexpensive
      method.

PMID- 29320718
TI  - Adiposity and family history of type 2 diabetes in an admixed population of
      adolescents: Associations with insulin sensitivity, beta-cell function, and
      hepatic insulin extraction in BRAMS study.
AB  - AIMS: Insulin resistance and beta-cell dysfunction manifest differently across
      racial/ethnic groups, and there is a lack of knowledge regarding the
      pathophysiology of type 2 diabetes mellitus (T2DM) for ethnically admixed
      adolescents. This study aimed to investigate the influence of adiposity and
      family history (FH) of T2DM on aspects of insulin sensitivity, beta-cell
      function, and hepatic insulin extraction in Brazilian adolescents. METHODS: A
      total of 82 normoglycemic adolescents were assessed. The positive FH of T2DM was
      defined as the presence of at least one known family member with T2DM. The
      hyperglycemic clamp test consisted of a 120-min protocol. Insulin secretion and
      beta-cell function were obtained from C-peptide deconvolution. Analysis of
      covariance considered pubertal stage as a covariate. RESULTS: Both lean and
      overweight/obese adolescents had similar glycemic profiles and disposition
      indexes. Overweight/obese adolescents had about 1/3 the insulin sensitivity of
      lean adolescents (1.1 +/- 0.2 vs. 3.4 +/- 0.3 mg.kg.min.pmol * 1000), which was
      compensated by an increase around 2.5 times in basal (130 +/- 7 vs. 52 +/- 10
      pmol.l.min) and total insulin secretion (130,091 +/- 12,230 vs. 59,010 +/- 17,522
      pmol.l.min), and in the first and second phases of insulin secretion;
      respectively (p < 0.001). This increase was accompanied by a mean reduction in
      hepatic insulin extraction of 35%, and a 2.7-time increase in beta-cell glucose
      sensitivity (p < 0.05). The positive FH of T2DM was not associated with
      derangements in insulin sensitivity, beta-cell function, and hepatic insulin
      extraction. CONCLUSIONS: In an admixed sample of adolescents, the hyperglycemic
      clamp test demonstrated that adiposity had a strong influence, and FH of T2DM had
      no direct influence, in different aspects of glucose metabolism.

PMID- 29320719
TI  - Genetic diversity of Cryptosporidium isolates from human populations in an urban
      area of Northern Tunisia.
AB  - Cryptosporidium is an enteric parasite infecting a wide range of hosts. It has
      emerged as an important cause of chronic life-threatening diarrhea in humans
      worldwide. Several subtypes of Cryptosporidium sp. have been described to be
      responsible for several large outbreaks related to water contamination in
      developed countries. However, there is a lack of information in the genetic
      diversity of Cryptosporidium among human population especially in developing
      countries. The present study aimed to update and report the genetic diversity of
      human Cryptosporidium spp. at the subtype level in an urban area of Tunisia using
      the 18S rRNA and gp60 gene. Genotyping of 42 Cryptosporidium positive isolates
      from different human populations at the 18S rRNA locus has identified three
      Cryptosporidium species: C. hominis (n = 20), C. parvum (n = 19), C. meleagridis
      (n = 2) and a co-infection C. hominis/C. meleagridis (n = 1). The sub-genotyping
      of these isolates at the 60-kda glycoprotein (gp60) locus was possible in 40
      cases. It showed the presence of three subtype families (IIa, IIb and IIc) within
      C. parvum, a single subtype family within C. hominis and C. meleagridis isolates
      (Ia and IIIb respectively). Several subtypes were implicated in different human
      populations with the dominance of IaA26G1R1, IIaA15G2R1, IIdA16G1R1, IIdA22G2R1
      and IIIbA26G1R1 variant respectively for C. hominis, C. parvum and C.
      meleagridis. The distribution of Cryptosporidium isolates in urban area of
      Northern Tunisia was dominated by the anthroponotic transmission via C. hominis
      species and the IIc subtype of C. parvum. However, zoonotic transmission is still
      possible in this region via zoonotic subtypes of C. parvum (IIa and IId) and C.
      meleagridis (IIIb). Subtype diversity was higher in this area.

PMID- 29320720
TI  - Simultaneous emergence and rapid spread of three OXA-23 producing Acinetobacter
      baumannii ST208 strains in intensive care units confirmed by whole genome
      sequencing.
AB  - Carbapenem-resistant Acinetobacter baumannii (CRAB) is a common nosocomial
      bacterial pathogen with limited treatment options. CRAB outbreaks are disastrous
      for critically ill patients. This study investigated carbapenemase-produced A.
      baumannii outbreaks in a tertiary hospital. Although multiple outbreaks were
      suggested by pulse-field gel electrophoresis, the genetic lineages and evolution
      between these isolates were not clear. To investigate the genomic epidemiology of
      these outbreaks and to reveal possible transmission routes, whole genome
      sequences (WGS) were compared and analyzed. From the WGS data, thirty isolates
      had the same sequence type (ST208); acquired resistance genes and chromosome
      resistant genes were detected and were responsible for multidrug resistance. A
      phylogenetic tree of single-nucleotide polymorphisms (SNPs) compared to the
      earliest index isolate found that three outbreaks had emerged and disseminated
      simultaneously. Of these, <10 SNPs were detected within the cluster, whereas at
      least 600 SNPs were found between the clusters. The probable transmission routes
      of outbreaks were generated combined with the genetic distance of isolates and
      patient epidemiological data. In conclusion, WGS was a convenient and accurate
      monitoring method for genomic epidemiologic investigation of outbreaks, and the
      genomic surveillance of multidrug-resistant bacterial pathogens would be a
      powerful warning system for the surveillance and prevention of outbreaks.

PMID- 29320721
TI  - Strong and biocompatible three-dimensional porous silk fibroin/graphene oxide
      scaffold prepared by phase separation.
AB  - Silk fibroin (SF) is blended with graphene oxide (GO) to prepare the strong and
      biocompatible three dimensional porous SF/GO blended scaffold via phase
      separation. GO could be well dispersed in SF solution and GO could also be well
      distributed in the SF scaffold. Furthermore, the introduction of GO can lead to
      structural change in the bended scaffold. Higher concentration of GO resulted in
      more compact structure and smaller pore size of the composite scaffolds without
      decreasing their porosity. Scanning electron microscopy and energy dispersive
      spectrometry results also reveal that SF and GO are homogeneous blended together.
      Analysis of chemical structures of the scaffold shows that addition of GO do not
      affect the crystalline structure of SF and it is evenly blended with SF. The
      blended scaffold has significantly higher breaking strength than the pure SF
      scaffold. In vitro study indicates that both pure SF scaffold and SF/GO composite
      scaffold support growth and proliferation of MC3T3-E1 osteoprogenitor cells.
      However, the addition of GO contribute to the proliferation of MC3T3-E1
      osteoprogenitor. The testing results show that the blended scaffold is an
      appropriate candidate for tissue engineering.

PMID- 29320722
TI  - Biodegradation and ecotoxicological impact of cellulose nanocomposites in
      municipal solid waste composting.
AB  - Biodegradable nanocomposites were prepared from polyvinyl alcohol (PVA) and
      cellulose nanofiber (CNF) by using liquid nitrogen, freeze drying and hot press
      techniques. The effect of CNF content on the biodegradability of the films was
      investigated by visual observation, scanning electron microscopy (SEM), weight
      loss, CO2 evolution, differential scanning calorimetry, measuring the amount of
      mineralized carbon of the specimens buried in municipal solid waste. Ecotoxicity
      was evaluated by plants growth tests with cress and spinach. The results
      confirmed that the weight loss of nanocomposites was lower than that of neat PVA
      because of the zigzag pathways of microorganisms in the CNF presence. The SEM
      analysis showed extensive surface roughness and cracks for all samples,
      indicating the initiation of biodegradation. The CO2 evolution decreased with
      increasing CNF content from 0% to 10% and then, increased with further increase
      in the filler content (up to 30 wt%). The crystallinity of the PVA and its
      nanocomposites increased as a function of time because of the amorphous parts
      degradation. Preliminary results of the ecotoxicological test revealed that all
      the nanocomposites and neat PVA did not generate any negative effects on
      germination or development of the studied vegetal species.

PMID- 29320723
TI  - Comparative study of structural and functional characterization of bran protein
      concentrates from superfine, fine and coarse rice cultivars.
AB  - Rice bran protein concentrates prepared from superfine, fine and coarse cultivars
      were assessed for their physicochemical, structural, functional properties and
      digestibility. The protein concentrates differed in structural, thermal and
      functional properties. Rice bran protein concentrate of fine cultivar (F-RBPC)
      had relatively more beta-sheets (42.81%) and less alpha-helix (15.03%) and beta
      turns (21.98%) than that of superfine (SF-RBPC) and coarse (C-RBPC) cultivars.
      Thermal denaturation temperature (Td) was similar for all cultivars, whereas
      enthalpy of denaturation (DeltaH) was high for F-RBPC. Essential and uncharged
      polar amino acids were the highest in F-RBPC and the lowest in C-RBPC. SF-RBPC
      had higher digestibility in comparison to F-RBPC and C-RBPC. Surface
      hydrophobicity, protein solubility and foaming capacity were greatest for F-RBPC.
      Whereas, SF-RBPC exhibited better foaming stability and emulsion activity and C
      RBPC displayed more stable emulsion. Principal component analysis revealed that
      Td and DeltaH were positively correlated with beta-sheets content. Foaming
      capacity and protein solubility were related positively with surface
      hydrophobicity and negatively charged or uncharged polar amino acids. Emulsion
      properties were negatively correlated with hydrophobicity. In vitro digestibility
      of protein was negatively correlated to the ratio of Arginine to Lysine.

PMID- 29320724
TI  - Purification and characterization of a novel high molecular weight alkaline
      protease produced by an endophytic Bacillus halotolerans strain CT2.
AB  - A protease-producing strain CT2 isolated from Tunisian potatoes, exhibiting a
      potent protease activity (prot CT2), was identified as Bacillus halotolerans
      according to 16S ribosomal DNA sequence analysis. Maximum prot CT2 production was
      obtained in medium supplemented with bean seed proteins. Proteolytic activity was
      purified by ammonium sulphate precipitation, Sephacryl S-200 gel filtration and
      SP-sepharose cation-exchange chromatography. Optimal enzyme activity was reached
      at pH 9 and temperature of 50  degrees C. Proteolytic activity was enhanced by
      Ca2+ and Mn2+ ions, completely inhibited by PMSF suggesting a serine protease
      nature and exhibited high stability in the presence of commercial detergents.
      Prot CT2 showed broad substrate specificity towards both synthetic and natural
      substrates, with a high capacity to hydrolyze legume seed proteins. Using
      electrophoretic analysis, its molecular weight was around 250 kDa with two major
      subunit showing important homologies with serine proteases belonging to the
      subtilisin-like serine proteases. Based on the Lineweaver-Burk plots Km and Vmax
      values were 10 mg/ml and 50,000 U/mg respectively. This newly described prot CT2
      displays relevant properties which highlight its potential use in various
      industrial and biotechnological applications.

PMID- 29320725
TI  - Keratin based bioplastic film from chicken feathers and its characterization.
AB  - Plastics have been one of the highly valued materials and it plays an significant
      role in human's life such as in food packaging and biomedical applications.
      Bioplastic materials can gradually work as a substitute for various materials
      based on fossil oil. The issue like sustainability and environmental challenges
      which occur due to manufacturing and disposal of synthetic plastics can be
      conquering by bio-based plastics. Feathers are among the most inexpensive
      abundant, and renewable protein sources. Feathers disposal to the landfills leads
      to environmental pollutions and it results into wastage of 90% of protein raw
      material. Keratin is non-burning hydrophilic, and biodegradable due to which it
      can be applicable in various ways via chemical processing. Main objective of this
      research is to synthesis bioplastic using keratin from chicken feathers.
      Extracted keratin solution mixed with different concentration of glycerol (2 to
      10%) to produce plastic films. The mixture was stirred under constant magnetic
      stirring at 60  degrees C for 5 h. The mixtures are then poured into aluminum
      weighing boat and dried in an oven at 60  degrees C for 24 h. The mechanical
      properties of the samples were tested and the physic-chemical properties of the
      bioplastic were studied. According to the results, Scanning Electron Microscopy
      test showed good compatible morphologies without holes, cavity and edge. The
      difference in chemical composition was analyzed using Fourier transform infrared
      spectroscopy (FTIR). The samples were also characterized by thermo gravimetric
      analysis (TGA), differential scanning calorimetry (DSC), X-Ray diffraction (XRD)
      to check the thermal and crystallinity properties. Other than that, bioplastic
      made up from keratin with 2% of glycerol has the best mechanical and thermal
      properties. According to biodegradability test, all bioplastic produced are
      proven biodegradable. Therefore, the results showed possible application of the
      film as an alternative to fossil oil based materials which are harmful to the
      environment.

PMID- 29320726
TI  - Pullulanase treatments to increase resistant starch content of black chickpea
      (Cicer arietinum L.) starch and the effects on starch properties.
AB  - This study aimed to increase resistant starch (RS) content of black chickpeas
      (Cicer arietinum L.) by using pullulanase enzyme. Physicochemical and functional
      properties of enzyme treated starch (NE) was compared with that of enzyme-treated
      and gelatinized starch (GE) and the retrograded control starch (RC). RS contents
      for native black chickpea starch (NS) and black chickpea flour (NF) were measured
      as 15.2% and 5.0%, respectively. While for NE and GE, were found as 16.4% and
      12.3%, respectively. Treatments made on the NS, increased the amount of RDS and
      reduced the amount of SDS significantly (p < .05). When the effect of enzyme
      application-autoclaving and retrogradation were compared, 41.3% increase in RS
      content was measured. In this study; RS3 production from black chickpea starch by
      a pullulanase enzyme was successfully performed. Enzymatic applications also
      improved the functional properties such as water absorption capacity, water
      solubility index value, fat binding capacity and emulsifying capacity. This
      enzyme treated black chickpea starch samples, being functionally improved, will
      possibly help to produce different products with desired quality parameters.
      Therefore, instead of native starch, pullulanase treated black chickpea starch
      may be used as a functional ingredient for increasing the amount of RS in food
      formulations.

PMID- 29320727
TI  - Polysaccharide structure and immunological relationships of RG-I pectin from the
      bee pollen of Nelumbo nucifera.
AB  - From the bee pollen of Nelumbo nucifera, we used hot water extraction and
      chromatographic fractionation on DEAE-cellulose and Sepharose CL-6B to purify
      polysaccharides (WNPP) to homogeneity. WNPP-2-RG (3.8 * 105 Da) consisted
      primarily of Rha (11.5%), GalA (12.0%), Gal (41.2%) and Ara (29.7%). Structure
      analysis showed that this polysaccharide is a RG-I type pectin containing AG-I
      and AG-II side chains comprised of 1,5-L-Ara (25.6%), t-D-Gal (12.0%), and 1,6-D
      Gal (18.3%) as the primary linkage types. Immunological activity assays
      demonstrated that WNPP-2-RG increased lymphocyte proliferation and macrophage
      phagocytosis, and induced production of NO. Compared to WNPP-2-RG, its
      hydrolysates (RG-8H-P) had no effect on lymphocyte proliferation, although they
      did promote macrophage phagocytosis and decreased NO production. Our results
      suggest that Gal side chain residues may play a crucial role in macrophage
      phagocytosis, whereas Ara is unimportant for NO production and neither Gal nor
      Ara impact lymphocyte proliferation.

PMID- 29320728
TI  - In Vivo Function of the Chaperonin TRiC in alpha-Actin Folding during Sarcomere
      Assembly.
AB  - The TCP-1 ring complex (TRiC) is a multi-subunit group II chaperonin that assists
      nascent or misfolded proteins to attain their native conformation in an ATP
      dependent manner. Functional studies in yeast have suggested that TRiC is an
      essential and generalized component of the protein-folding machinery of
      eukaryotic cells. However, TRiC's involvement in specific cellular processes
      within multicellular organisms is largely unknown because little validation of
      TRiC function exists in animals. Our in vivo analysis reveals a surprisingly
      specific role of TRiC in the biogenesis of skeletal muscle alpha-actin during
      sarcomere assembly in myofibers. TRiC acts at the sarcomere's Z-disk, where it is
      required for efficient assembly of actin thin filaments. Binding of ATP
      specifically by the TRiC subunit Cct5 is required for efficient actin folding in
      vivo. Furthermore, mutant alpha-actin isoforms that result in nemaline myopathy
      in patients obtain their pathogenic conformation via this function of TRiC.

PMID- 29320729
TI  - Corneal-Committed Cells Restore the Stem Cell Pool and Tissue Boundary following
      Injury.
AB  - During morphogenesis, preserving tissue boundaries is essential for cell fate
      regulation. While embryonic tissues possess high plasticity and repair ability,
      the questions of whether and how adult tissues cope with acute stem cell (SC)
      loss or boundary disruption have remained unanswered. Here, we report that K15
      GFP transgene labels the murine corneal epithelial boundary and SC niche known as
      the limbus. K15-GFP+ basal cells expressed SC markers and were located at the
      corneal regeneration site, as evident by lineage tracing. Remarkably, following
      surgical deletion of the SC pool, corneal-committed cells dedifferentiated into
      bona fide limbal SCs that retained normal tissue dynamics and marker expression.
      Interestingly, however, damage to the limbal stromal niche abolished K15-GFP
      recovery and led to pathological wound healing. Altogether, this study indicates
      that committed corneal cells possess plasticity to dedifferentiate, repopulate
      the SC pool, and correctly re-form the tissue boundary in the presence of intact
      stroma.

PMID- 29320730
TI  - Esrrb Complementation Rescues Development of Nanog-Null Germ Cells.
AB  - The transcription factors (TFs) Nanog and Esrrb play important roles in embryonic
      stem cells (ESCs) and during primordial germ-cell (PGC) development. Esrrb is a
      positively regulated direct target of NANOG in ESCs that can substitute
      qualitatively for Nanog function in ESCs. Whether this functional substitution
      extends to the germline is unknown. Here, we show that germline deletion of Nanog
      reduces PGC numbers 5-fold at midgestation. Despite this quantitative depletion,
      Nanog-null PGCs can complete germline development in contrast to previous
      findings. PGC-like cell (PGCLC) differentiation of Nanog-null ESCs is also
      impaired, with Nanog-null PGCLCs showing decreased proliferation and increased
      apoptosis. However, induced expression of Esrrb restores PGCLC numbers as
      efficiently as Nanog. These effects are recapitulated in vivo: knockin of Esrrb
      to Nanog restores PGC numbers to wild-type levels and results in fertile adult
      mice. These findings demonstrate that Esrrb can replace Nanog function in germ
      cells.

PMID- 29320731
TI  - Durable Interactions of T Cells with T Cell Receptor Stimuli in the Absence of a
      Stable Immunological Synapse.
AB  - T cells engage in two modes of interaction with antigen-presenting surfaces:
      stable synapses and motile kinapses. Although it is surmised that durable
      interactions of T cells with antigen-presenting cells involve synapses, in situ
      3D imaging cannot resolve the mode of interaction. We have established in vitro
      2D platforms and quantitative metrics to determine cell-intrinsic modes of
      interaction when T cells are faced with spatially continuous or restricted
      stimulation. All major resting human T cell subsets, except memory CD8 T cells,
      spend more time in the kinapse mode on continuous stimulatory surfaces.
      Surprisingly, we did not observe any concordant relationship between the mode and
      durability of interaction on cell-sized stimulatory spots. Naive CD8 T cells
      maintain kinapses for more than 3 hr before leaving stimulatory spots, whereas
      their memory counterparts maintain synapses for only an hour before leaving.
      Thus, durable interactions do not require stable synapses.

PMID- 29320733
TI  - DNA Unwinding Is the Primary Determinant of CRISPR-Cas9 Activity.
AB  - Bacterial adaptive immunity utilizes RNA-guided surveillance complexes comprising
      Cas proteins together with CRISPR RNAs (crRNAs) to target foreign nucleic acids
      for destruction. Cas9, a type II CRISPR-Cas effector complex, can be programed
      with a single-guide RNA that base pairs with the target strand of dsDNA,
      displacing the non-target strand to create an R-loop, where the HNH and the RuvC
      nuclease domains cleave opposing strands. While many structural and biochemical
      studies have shed light on the mechanism of Cas9 cleavage, a clear unifying model
      has yet to emerge. Our detailed kinetic characterization of the enzyme reveals
      that DNA binding is reversible, and R-loop formation is rate-limiting, occurring
      in two steps, one for each of the nuclease domains. The specificity constant for
      cleavage is determined through an induced-fit mechanism as the product of the
      equilibrium binding affinity for DNA and the rate of R-loop formation.

PMID- 29320732
TI  - Stabilization of NF-kappaB-Inducing Kinase Suppresses MLL-AF9-Induced Acute
      Myeloid Leukemia.
AB  - Canonical NF-kappaB signaling is constitutively activated in acute myeloid
      leukemia (AML) stem cells and is required for maintenance of the self-renewal of
      leukemia stem cells (LSCs). However, any potential role for NF-kappaB non
      canonical signaling in AML has been largely overlooked. Here, we report that
      stabilization of NF-kappaB-inducing kinase (NIK) suppresses AML. Mechanistically,
      stabilization of NIK activates NF-kappaB non-canonical signaling and represses NF
      kappaB canonical signaling. In addition, stabilization of NIK-induced activation
      of NF-kappaB non-canonical signaling upregulates Dnmt3a and downregulates Mef2c,
      which suppresses and promotes AML development, respectively. Importantly, by
      querying the connectivity MAP using up- and downregulated genes that are present
      exclusively in NIK-stabilized LSCs, we discovered that verteporfin has anti-AML
      effects, suggesting that repurposing verteporfin to target myeloid leukemia is
      worth testing clinically. Our data provide a scientific rationale for developing
      small molecules to stabilize NIK specifically in myeloid leukemias as an
      attractive therapeutic option.

PMID- 29320734
TI  - The Conformational Dynamics of Cas9 Governing DNA Cleavage Are Revealed by Single
      Molecule FRET.
AB  - Off-target binding and cleavage by Cas9 pose major challenges in its application.
      How the conformational dynamics of Cas9 govern its nuclease activity under on-
      and off-target conditions remains largely unknown. Here, using intra-molecular
      single-molecule fluorescence resonance energy transfer measurements, we revealed
      that Cas9 in apo, sgRNA-bound, and dsDNA/sgRNA-bound forms spontaneously transits
      among three major conformational states, mainly reflecting significant
      conformational mobility of the catalytic HNH domain. We also uncovered surprising
      long-range allosteric communication between the HNH domain and the RNA/DNA
      heteroduplex at the PAM-distal end to ensure correct positioning of the catalytic
      site, which demonstrated that a unique proofreading mechanism served as the last
      checkpoint before DNA cleavage. Several Cas9 residues were likely to mediate the
      allosteric communication and proofreading step. Modulating interactions between
      Cas9 and heteroduplex at the PAM-distal end by introducing mutations on these
      sites provides an alternative route to improve and optimize the CRISPR/Cas9
      toolbox.

PMID- 29320735
TI  - RYBP Is a K63-Ubiquitin-Chain-Binding Protein that Inhibits Homologous
      Recombination Repair.
AB  - Ring1-YY1-binding protein (RYBP) is a member of the non-canonical polycomb
      repressive complex 1 (PRC1), and like other PRC1 members, it is best described as
      a transcriptional regulator. However, several PRC1 members were recently shown to
      function in DNA repair. Here, we report that RYBP preferentially binds K63
      ubiquitin chains via its Npl4 zinc finger (NZF) domain. Since K63-linked
      ubiquitin chains are assembled at DNA double-strand breaks (DSBs), we examined
      the contribution of RYBP to DSB repair. Surprisingly, we find that RYBP is K48
      polyubiquitylated by RNF8 and rapidly removed from chromatin upon DNA damage by
      the VCP/p97 segregase. High expression of RYBP competitively inhibits recruitment
      of BRCA1 repair complex to DSBs, reducing DNA end resection and homologous
      recombination (HR) repair. Moreover, breast cancer cell lines expressing high
      endogenous RYBP levels show increased sensitivity to DNA-damaging agents and poly
      ADP-ribose polymerase (PARP) inhibition. These data suggest that RYBP negatively
      regulates HR repair by competing for K63-ubiquitin chain binding.

PMID- 29320736
TI  - The RNA Polymerase II Factor RPAP1 Is Critical for Mediator-Driven Transcription
      and Cell Identity.
AB  - The RNA polymerase II-associated protein 1 (RPAP1) is conserved across metazoa
      and required for stem cell differentiation in plants; however, very little is
      known about its mechanism of action or its role in mammalian cells. Here, we
      report that RPAP1 is essential for the expression of cell identity genes and for
      cell viability. Depletion of RPAP1 triggers cell de-differentiation, facilitates
      reprogramming toward pluripotency, and impairs differentiation. Mechanistically,
      we show that RPAP1 is essential for the interaction between RNA polymerase II
      (RNA Pol II) and Mediator, as well as for the recruitment of important
      regulators, such as the Mediator-specific RNA Pol II factor Gdown1 and the C
      terminal domain (CTD) phosphatase RPAP2. In agreement, depletion of RPAP1
      diminishes the loading of total and Ser5-phosphorylated RNA Pol II on many genes,
      with super-enhancer-driven genes among the most significantly downregulated. We
      conclude that Mediator/RPAP1/RNA Pol II is an ancient module, conserved from
      plants to mammals, critical for establishing and maintaining cell identity.

PMID- 29320738
TI  - Trapping of Syntaxin1a in Presynaptic Nanoclusters by a Clinically Relevant
      General Anesthetic.
AB  - Propofol is the most commonly used general anesthetic in humans. Our
      understanding of its mechanism of action has focused on its capacity to
      potentiate inhibitory systems in the brain. However, it is unknown whether other
      neural mechanisms are involved in general anesthesia. Here, we demonstrate that
      the synaptic release machinery is also a target. Using single-particle tracking
      photoactivation localization microscopy, we show that clinically relevant
      concentrations of propofol and etomidate restrict syntaxin1A mobility on the
      plasma membrane, whereas non-anesthetic analogs produce the opposite effect and
      increase syntaxin1A mobility. Removing the interaction with the t-SNARE partner
      SNAP-25 abolishes propofol-induced syntaxin1A confinement, indicating that
      syntaxin1A and SNAP-25 together form an emergent drug target. Impaired syntaxin1A
      mobility and exocytosis under propofol are both rescued by co-expressing a
      truncated syntaxin1A construct that interacts with SNAP-25. Our results suggest
      that propofol interferes with a step in SNARE complex formation, resulting in non
      functional syntaxin1A nanoclusters.

PMID- 29320737
TI  - Genomic Circuitry Underlying Immunological Response to Pediatric Acute
      Respiratory Infection.
AB  - Acute respiratory tract viral infections (ARTIs) cause significant morbidity and
      mortality. CD8 T cells are fundamental to host responses, but transcriptional
      alterations underlying anti-viral mechanisms and links to clinical
      characteristics remain unclear. CD8 T cell transcriptional circuitry in acutely
      ill pediatric patients with influenza-like illness was distinct for different
      viral pathogens. Although changes included expected upregulation of interferon
      stimulated genes (ISGs), transcriptional downregulation was prominent upon
      exposure to innate immune signals in early IFV infection. Network analysis linked
      changes to severity of infection, asthma, sex, and age. An influenza pediatric
      signature (IPS) distinguished acute influenza from other ARTIs and outperformed
      other influenza prediction gene lists. The IPS allowed a deeper investigation of
      the connection between transcriptional alterations and clinical characteristics
      of acute illness, including age-based differences in circuits connecting the
      STAT1/2 pathway to ISGs. A CD8 T cell-focused systems immunology approach in
      pediatrics identified age-based alterations in ARTI host response pathways.

PMID- 29320739
TI  - Variation in Activity State, Axonal Projection, and Position Define the
      Transcriptional Identity of Individual Neocortical Projection Neurons.
AB  - Single-cell RNA sequencing has generated catalogs of transcriptionally defined
      neuronal subtypes of the brain. However, the cellular processes that contribute
      to neuronal subtype specification and transcriptional heterogeneity remain
      unclear. By comparing the gene expression profiles of single layer 6
      corticothalamic neurons in somatosensory cortex, we show that transcriptional
      subtypes primarily reflect axonal projection pattern, laminar position within the
      cortex, and neuronal activity state. Pseudotemporal ordering of 1,023 cellular
      responses to sensory manipulation demonstrates that changes in expression of
      activity-induced genes both reinforced cell-type identity and contributed to
      increased transcriptional heterogeneity within each cell type. This is due to
      cell-type biased choices of transcriptional states following manipulation of
      neuronal activity. These results reveal that axonal projection pattern, laminar
      position, and activity state define significant axes of variation that contribute
      both to the transcriptional identity of individual neurons and to the
      transcriptional heterogeneity within each neuronal subtype.

PMID- 29320741
TI  - Endocytosis of KATP Channels Drives Glucose-Stimulated Excitation of Pancreatic
      beta Cells.
AB  - Insulin secretion from pancreatic beta cells in response to high glucose (HG)
      critically depends on the inhibition of KATP channel activity in HG. It is
      generally believed that HG-induced effects are mediated by the increase in
      intracellular ATP, but here, we showed that, in INS-1 cells, endocytosis of KATP
      channel plays a major role. Upon HG stimulation, resting membrane potential
      depolarized by 30.6 mV (from -69.2 to -38.6 mV) and KATP conductance decreased by
      91% (from 0.243 to 0.022 nS/pF), whereas intracellular ATP was increased by only
      47%. HG stimulation induced internalization of KATP channels, causing a
      significant decrease in surface channel density, and this decrease was completely
      abolished by inhibiting endocytosis using dynasore, a dynamin inhibitor, or a PKC
      inhibitor. These drugs profoundly inhibited HG-induced depolarization. Our
      results suggest that the control of KATP channel surface density plays a greater
      role than ATP-dependent gating in regulating beta cell excitability.

PMID- 29320740
TI  - PlexinA2 Forward Signaling through Rap1 GTPases Regulates Dentate Gyrus
      Development and Schizophrenia-like Behaviors.
AB  - Dentate gyrus (DG) development requires specification of granule cell (GC)
      progenitors in the hippocampal neuroepithelium, as well as their proliferation
      and migration into the primordial DG. We identify the Plexin family members
      Plxna2 and Plxna4 as important regulators of DG development. Distribution of
      immature GCs is regulated by Sema5A signaling through PlxnA2 and requires a
      functional PlxnA2 GTPase-activating protein (GAP) domain and Rap1 small GTPases.
      In adult Plxna2-/- but not Plxna2-GAP-deficient mice, the dentate GC layer is
      severely malformed, neurogenesis is compromised, and mossy fibers form aberrant
      synaptic boutons within CA3. Behavioral studies with Plxna2-/- mice revealed
      deficits in associative learning, sociability, and sensorimotor gating-traits
      commonly observed in neuropsychiatric disorder. Remarkably, while morphological
      defects are minimal in Plxna2-GAP-deficient brains, defects in fear memory and
      sensorimotor gating persist. Since allelic variants of human PLXNA2 and RAP1
      associate with schizophrenia, our studies identify a biochemical pathway
      important for brain development and mental health.

PMID- 29320742
TI  - Defective Mitochondrial tRNA Taurine Modification Activates Global Proteostress
      and Leads to Mitochondrial Disease.
AB  - A subset of mitochondrial tRNAs (mt-tRNAs) contains taurine-derived modifications
      at 34U of the anticodon. Loss of taurine modification has been linked to the
      development of mitochondrial diseases, but the molecular mechanism is still
      unclear. Here, we showed that taurine modification is catalyzed by mitochondrial
      optimization 1 (Mto1) in mammals. Mto1 deficiency severely impaired mitochondrial
      translation and respiratory activity. Moreover, Mto1-deficient cells exhibited
      abnormal mitochondrial morphology owing to aberrant trafficking of nuclear DNA
      encoded mitochondrial proteins, including Opa1. The mistargeted proteins were
      aggregated and misfolded in the cytoplasm, which induced cytotoxic unfolded
      protein response. Importantly, application of chemical chaperones successfully
      suppressed cytotoxicity by reducing protein misfolding and increasing functional
      mitochondrial proteins in Mto1-deficient cells and mice. Thus, our results
      demonstrate the essential role of taurine modification in mitochondrial
      translation and reveal an intrinsic protein homeostasis network between the
      mitochondria and cytosol, which has therapeutic potential for mitochondrial
      diseases.

PMID- 29320743
TI  - A p300 and SIRT1 Regulated Acetylation Switch of C/EBPalpha Controls
      Mitochondrial Function.
AB  - Cellular metabolism is a tightly controlled process in which the cell adapts
      fluxes through metabolic pathways in response to changes in nutrient supply.
      Among the transcription factors that regulate gene expression and thereby cause
      changes in cellular metabolism is the basic leucine-zipper (bZIP) transcription
      factor CCAAT/enhancer-binding protein alpha (C/EBPalpha). Protein lysine
      acetylation is a key post-translational modification (PTM) that integrates
      cellular metabolic cues with other physiological processes. Here, we show that
      C/EBPalpha is acetylated by the lysine acetyl transferase (KAT) p300 and
      deacetylated by the lysine deacetylase (KDAC) sirtuin1 (SIRT1). SIRT1 is
      activated in times of energy demand by high levels of nicotinamide adenine
      dinucleotide (NAD+) and controls mitochondrial biogenesis and function. A
      hypoacetylated mutant of C/EBPalpha induces the transcription of mitochondrial
      genes and results in increased mitochondrial respiration. Our study identifies
      C/EBPalpha as a key mediator of SIRT1-controlled adaption of energy homeostasis
      to changes in nutrient supply.

PMID- 29320744
TI  - Consumption of NADPH for 2-HG Synthesis Increases Pentose Phosphate Pathway Flux
      and Sensitizes Cells to Oxidative Stress.
AB  - Gain-of-function mutations in isocitrate dehydrogenase 1 (IDH1) occur in multiple
      types of human cancer. Here, we show that these mutations significantly disrupt
      NADPH homeostasis by consuming NADPH for 2-hydroxyglutarate (2-HG) synthesis.
      Cells respond to 2-HG synthesis, but not exogenous administration of 2-HG, by
      increasing pentose phosphate pathway (PPP) flux. We show that 2-HG production
      competes with reductive biosynthesis and the buffering of oxidative stress,
      processes that also require NADPH. IDH1 mutants have a decreased capacity to
      synthesize palmitate and an increased sensitivity to oxidative stress. Our
      results demonstrate that, even when NADPH is limiting, IDH1 mutants continue to
      synthesize 2-HG at the expense of other NADPH-requiring pathways that are
      essential for cell viability. Thus, rather than attempting to decrease 2-HG
      synthesis in the clinic, the consumption of NADPH by mutant IDH1 may be exploited
      as a metabolic weakness that sensitizes tumor cells to ionizing radiation, a
      commonly used anti-cancer therapy.

PMID- 29320745
TI  - The Foxo1-Inducible Transcriptional Repressor Zfp125 Causes Hepatic Steatosis and
      Hypercholesterolemia.
AB  - Liver-specific disruption of the type 2 deiodinase gene (Alb-D2KO) results in
      resistance to both diet-induced obesity and liver steatosis in mice. Here, we
      report that this is explained by an ~60% reduction in liver zinc-finger protein
      125 (Zfp125) expression. Zfp125 is a Foxo1-inducible transcriptional repressor
      that causes lipid accumulation in the AML12 mouse hepatic cell line and liver
      steatosis in mice by reducing liver secretion of triglycerides and hepatocyte
      efflux of cholesterol. Zfp125 acts by repressing 18 genes involved in lipoprotein
      structure, lipid binding, and transport. The ApoE promoter contains a functional
      Zfp125-binding element that is also present in 17 other lipid-related genes
      repressed by Zfp125. While liver-specific knockdown of Zfp125 causes an "Alb-D2KO
      like" metabolic phenotype, liver-specific normalization of Zfp125 expression in
      Alb-D2KO mice rescues the phenotype, restoring normal susceptibility to diet
      induced obesity, liver steatosis, and hypercholesterolemia.

PMID- 29320746
TI  - SadA-Expressing Staphylococci in the Human Gut Show Increased Cell Adherence and
      Internalization.
AB  - A subgroup of biogenic amines, the so-called trace amines (TAs), are produced by
      mammals and bacteria and can act as neuromodulators. In the genus Staphylococcus,
      certain species are capable of producing TAs through the activity of
      staphylococcal aromatic amino acid decarboxylase (SadA). SadA decarboxylates
      aromatic amino acids to produce TAs, as well as dihydroxy phenylalanine and 5
      hydroxytryptophan to thus produce the neurotransmitters dopamine and serotonin.
      SadA-expressing staphylococci were prevalent in the gut of most probands, where
      they are part of the human intestinal microflora. Furthermore, sadA-expressing
      staphylococci showed increased adherence to HT-29 cells and 2- to 3-fold
      increased internalization. Internalization and adherence was also increased in a
      sadA mutant in the presence of tryptamine. The alpha2-adrenergic receptor is
      required for enhanced adherence and internalization. Thus, staphylococci in the
      gut might contribute to gut activity and intestinal colonization.

PMID- 29320747
TI  - Identification of Cardiomyocyte-Fated Progenitors from Human-Induced Pluripotent
      Stem Cells Marked with CD82.
AB  - Here, we find that human-induced pluripotent stem cell (hiPSC)-derived
      cardiomyocyte (CM)-fated progenitors (CFPs) that express a tetraspanin family
      glycoprotein, CD82, almost exclusively differentiate into CMs both in vitro and
      in vivo. CD82 is transiently expressed in late-stage mesoderm cells during hiPSC
      differentiation. Purified CD82+ cells gave rise to CMs under nonspecific in vitro
      culture conditions with serum, as well as in vivo after transplantation to the
      subrenal space or injured hearts in mice, indicating that CD82 successfully marks
      CFPs. CD82 overexpression in mesoderm cells as well as in undifferentiated hiPSCs
      increased the secretion of exosomes containing beta-catenin and reduced nuclear
      beta-catenin protein, suggesting that CD82 is involved in fated restriction to
      CMs through Wnt signaling inhibition. This study may contribute to the
      understanding of CM differentiation mechanisms and to cardiac regeneration
      strategies.

PMID- 29320748
TI  - True Molecular Scale Visualization of Variable Clustering Properties of Ryanodine
      Receptors.
AB  - Signaling nanodomains rely on spatial organization of proteins to allow
      controlled intracellular signaling. Examples include calcium release sites of
      cardiomyocytes where ryanodine receptors (RyRs) are clustered with their
      molecular partners. Localization microscopy has been crucial to visualizing these
      nanodomains but has been limited by brightness of markers, restricting the
      resolution and quantification of individual proteins clustered within. Harnessing
      the remarkable localization precision of DNA-PAINT (<10 nm), we visualized
      punctate labeling within these nanodomains, confirmed as single RyRs. RyR
      positions within sub-plasmalemmal nanodomains revealed how they are organized
      randomly into irregular clustering patterns leaving significant gaps occupied by
      accessory or regulatory proteins. RyR-inhibiting protein junctophilin-2 appeared
      highly concentrated adjacent to RyR channels. Analyzing these molecular maps
      showed significant variations in the co-clustering stoichiometry between
      junctophilin-2 and RyR, even between nearby nanodomains. This constitutes an
      additional level of complexity in RyR arrangement and regulation of calcium
      signaling, intrinsically built into the nanodomains.

PMID- 29320749
TI  - Atypical multivacuolated lipoblasts and atypical mitoses are not compatible with
      the diagnosis of spindle cell/pleomorphic lipoma-reply.

PMID- 29320750
TI  - The many faces of intestinal tract gastric heterotopia; a series of four cases
      highlighting clinical and pathological heterogeneity.
AB  - Gastric heterotopia of the intestinal tract can have a diverse clinicopathologic
      presentation, resulting in a diagnostic dilemma. We present a series of four
      cases, two male and two female patients with age range of 31-82 years, found in
      the duodenum, jejunum, and transverse colon. The most common and rather unusual
      clinical presentation was iron deficiency anemia, seen in three cases, while one
      patient presented with abdominal pain. Endoscopically, two cases were visualized
      as pedunculated polyps and two as sessile/plaque-like lesions. Polypectomy was
      performed in three patients, and one patient underwent biopsy followed by
      resection. Two cases showed oxyntic-type epithelium, and two cases exhibited
      pyloric-type gastric epithelium. Three patients were relieved of their presenting
      symptoms after therapeutic procedures with no evidence of recurrence noted on
      follow-up. Follow-up was not available on one patient. This case series
      highlights a diverse clinicopathologic spectrum of gastric heterotopia. Accurate
      diagnosis is essential for proper management.

PMID- 29320751
TI  - Uterine rhabdomyosarcoma in adults.
AB  - Rhabdomyosarcoma (RMS) is an aggressive mesenchymal tumor most commonly diagnosed
      in the pediatric population, and when occurring in adults, tends to develop in
      the deep soft tissue of the limbs. Primary uterine RMS comprises an even more
      restricted subset, with little known or reported when compared to most other
      gynecologic sarcomas. Our goal with this study was to retrospectively evaluate
      cases from two academic institutions and describe the main histopathologic
      findings of this rare gynecologic malignancy. A total of 8 cases were identified,
      consisting of 4 pleomorphic rhabdomyosarcomas (PRMS), 2 alveolar
      rhabdomyosarcomas (ARMS), and 2 embryonal rhabdomyosarcomas (ERMS). They occurred
      in patients ranging from 22 to 70 years old, and the most common presenting
      symptom was vaginal bleeding. Most patients presented with advanced stage at
      diagnosis, including metastatic disease to lymph nodes and to distant sites. The
      masses were mostly (6/8) centered in the myometrium, while two cases arose in the
      cervix (2/8). Histologic characteristics of the tumors were dependent on the RMS
      subtype, although all cases demonstrated a similar immunohistochemical profile
      regardless of their subclassification. RMS of the uterus has a very poor
      prognosis, and data regarding treatment of this rare malignancy is limited, and
      usually extrapolated from non-uterine sites.

PMID- 29320752
TI  - The value of detection of S100A8 and ASAH1 in predicting the chemotherapy
      response for breast cancer patients.
AB  - Chemotherapy plays an important role in the treatment of breast cancer. However,
      chemoresistance remains the main obstacle for effective treatment, leading to
      poor prognosis. This study aims to investigate the value of detection of S100A8
      and ASAH1 in predicting the chemotherapy response. Miller and Payne grades were
      used to assess the chemotherapy response in breast cancers. The expression of
      S100A8 and ASAH1, as well as ER, PR, HER2 and Ki-67 were assessed by
      immunohistochemical staining in 120 cases of non-special type invasive ductal
      carcinoma (IDC-NOS). S100A8 expression was higher in chemosensitive breast
      cancers than chemoresistant ones. Moreover, S100A8 expression was significantly
      correlated with the molecular subtypes and histological grade, but not with
      patients' age, tumor size and lymph nodes status. However, there was no
      significant difference in ASAH1 expression between chemoresistant and
      chemosensitive group. We also found that higher ASAH1 expression was correlated
      with positive lymph nodes status, but not with age, tumor size, molecular
      subtypes and histological grade. S100A8 was valuable in predicting chemotherapy
      response in breast cancers. The expression of ASAH1 was associated significantly
      with lymph nodes metastasis, indicating that ASAH1 may serve as a biomarker to
      predict patients' lymph nodes status in breast cancers.

PMID- 29320753
TI  - Prognostic significance of S100A16 subcellular localization in lung
      adenocarcinoma.
AB  - To discover novel tumor markers for lung adenocarcinoma (AC), we performed
      proteomics analysis and reported a correlation between S100A16 membranous
      expression in AC tissues and a poor prognosis. However, some patients with a good
      prognosis also showed S100A16 membranous staining. We re-evaluated
      immunohistochemically stained tissues, and found membrane-positive and nucleus
      negative expressions to be significantly higher in the presence of the following:
      male, smoker, positive nodal metastasis, higher p-TNM stage, larger tumor, poorer
      differentiation, positive for lymphatic invasion, positive for vascular invasion,
      and positive for pleural invasion (all factors P < .05). This pattern of staining
      was also an independent prognostic factor. Furthermore, we analyzed S100A16 mRNA
      expression using TCGA and Kaplan-Meier plotter databases, and found that higher
      S100A16 mRNA expression in AC was significantly correlated with poorer survival.
      To our knowledge, there has been no comprehensive study focused on both S100A16
      protein and mRNA expression levels in AC patients. Our results suggest that the
      subcellular localization of S100A16 and S100A16 mRNA expression levels is a
      promising prognostic marker for AC.

PMID- 29320754
TI  - Characteristics of cribriform morular variant of papillary thyroid carcinoma in
      post-Chernobyl affected region.
AB  - The aim is to study the characteristics of cribriform morular variant of
      papillary thyroid carcinoma (CMV-PTC) in patients living in the radiation
      affected area of Belarus. The clinical and pathological features of 35 patients
      with CMV-PTC from Belarus were studied and compared with those of conventional
      papillary thyroid carcinoma diagnosed in the same period. The patients with CMV
      PTC were all females and were younger at presentation (mean age = 24) than those
      with conventional papillary thyroid carcinoma. Familial adenomatous polyposis
      (FAP) was identified in 20% of the patients with CMV-PTC. The majority of the CMV
      PTCs (29/35; 83%) were staged as pT1 and were less advanced than conventional
      papillary thyroid carcinoma. There was no evidence of lymph node metastases or
      distant metastases. CMV-PTCs were positive for beta-catenin, APC (adenomatous
      polyposis coli) and p53 proteins. No psammoma bodies were identified on
      microscopic examination. Over a median follow-up of 9 years, all the patients
      were alive, and there was no cancer recurrence or mortality related to the
      thyroid cancer. To conclude, CMV-PTC in patients in the radiation-affected region
      behaves in an indolent fashion. They had distinctive features that are different
      from patients with conventional papillary thyroid carcinoma living in the same
      region.

PMID- 29320755
TI  - Downregulated SASH1 expression indicates poor clinical prognosis in gastric
      cancer.
AB  - SASH1 (SAM- and SH3-domain containing 1), a novel candidate tumor suppressor, has
      attracted attention due to its role in intracellular signal transduction and its
      tumor prognostic value in diverse cancers. Reports have demonstrated that reduced
      SASH1 expression correlates with tumor proliferation, invasion, and metastasis.
      However, the expression and prognostic significance of SASH1 in gastric cancer
      (GC) remain unclear. In this study, 8 paired fresh-frozen GC tissues and
      corresponding gastric mucosal tissues were examined by Western blot to analyze
      the protein expression of SASH1. Seven hundred twenty-six formalin-fixed,
      paraffin-embedded (FFPE) gastric tissue samples were evaluated by
      immunohistochemical (IHC) to determine the correlations of SASH1 expression with
      clinicopathological factors and prognosis. Compared with adjacent noncancerous
      tissues, SASH1 was significantly downregulated in GC specimens. Analysis using
      the chi2 test revealed that low SASH1 expression was significantly associated
      with advanced TNM stage (P < .001) in GC. Cox regression multivariable analyses
      demonstrated that SASH1 expression (P < .001), TNM stage (P < .001), preoperative
      CEA level (P = .003) and preoperative CA19-9 level (P = .002) were independent
      prognostic factors. Our clinical findings suggest that downregulated SASH1
      expression could be used as an independent biomarker for poor prognosis in GC.

PMID- 29320756
TI  - Generation of an induced pluripotent stem cell line from an adult male with
      45,X/46,XY mosaicism.
AB  - Turner syndrome (TS) with 45,X/46,XY mosaic karyotype is a rare sex chromosome
      disorder with an occurrence of 0.150/00 at birth. We report the generation of an
      induced pluripotent stem cell (iPSC) line from peripheral blood mononuclear cells
      of a Chinese adult male with 45,X/46,XY mosaicism. The iPSC line retains the
      original 45,X/46,XY mosaic karyotype, expresses pluripotency markers and
      undergoes trilineage differentiation. Therefore, it offers an unprecedented
      cellular model to investigate the profound symptoms like infertility of TS in the
      male, and serve as a useful tool to develop therapies for the disease.

PMID- 29320757
TI  - Expression of hNeuritin protein in a baculovirus expression system and the
      analysis of its activity.
AB  - Neuritin plays an important role in the development and regeneration of the
      nervous system, and shows good prospects in the treatment and protection of the
      nervous system. To characterize neuritin function, we constructed a baculovirus
      expression system of neuritin, and identified the biological activity of the
      neuritin protein. The results and showed that the expression product could
      promote the neurite growth of dorsal root ganglion in chicken embryos. The
      neuritin open reading frame was amplified and cloned into the plasmid
      pFastBacTMHTA. The pFastBacTMHTA-neuritin was confirmed to be correct by PCR and
      DNA sequencing, and then transformed into Escherichia coli DH10Bac. The high
      purity recombinant Bacmid-neuritin (shuttle vectors) was obtained from DH10Bac
      through screening and identification. Recombinant virus, including the neuritin
      gene (virus-neuritin), was produced by transfection of SF9 cells using the bacmid
      neuritin, and then amplified repeatedly to express the neuritin fusion protein.
      Finally, we identified the fusion protein with SDS-PAGE and western blotting, and
      optimized the best expression time of the neuritin fusion protein. We also
      analyzed the activity of the expressed protein by dorsal root ganglion from
      chicken embryos.

PMID- 29320758
TI  - Polymerase epsilon mutations and concomitant beta2-microglobulin mutations in
      cancer.
AB  - Mutations in the exonuclease domain of polymerase epsilon (POLE), an enzyme of
      DNA synthesis, are involved in a newly described syndrome of colorectal polyposis
      and cancer, and have been associated with a high mutation burden with or without
      microsatellite instability (MSI) phenotype. The exonuclease domain of POLE
      executes a proofreading function that decreases the mutation rate during DNA
      replication by an estimated of one to two orders. The high mutation burden
      resulting from its loss of function could create a load of neo-antigens that
      would put the neoplastic cells in severe disadvantage of an immune attack if
      properly presented to the immune system. This paper investigates the mutagenic
      effect of different POLE mutations in various cancers, in published genomic
      studies and the effect that these POLE mutations have in selecting for mutations
      of the beta2 microglobulin (B2M) gene involved in antigen presentation.

PMID- 29320759
TI  - Identification of key microRNAs affecting drip loss in porcine longissimus dorsi
      by RNA-Seq.
AB  - MicroRNAs (miRNAs) are a class of ~22-nt non-coding small RNA that play an
      important role in various metabolic processes, mainly through suppressing the
      expression of protein coding genes at post-transcriptional level. Drip loss (DL)
      is one of the most important meat quality traits affecting the end product yield
      and quality of pork. To date, the underlying regulatory factors involved in DL
      trait are still incompletely understood. In the present study, we constructed two
      small RNA libraries with longissimus dorsi muscles from the higher DL (WJJ-H
      group) and the lower DL (WJJ-L group) individuals, and applied RNA-Seq technology
      to identify the differentially expressed miRNAs between the two extreme
      phenotypes of DL groups. A total of 184 and 176 porcine known miRNAs were
      detected from WJJ-H and WJJ-L groups, respectively. Moreover, 73 differentially
      expressed miRNAs were identified between two groups, of which 40 were up
      regulated and 33 were down-regulated. In addition, 133 and 140 novel potential
      miRNAs were predicted from WJJ-H and WJJ-L groups, respectively. Notably, we
      preliminary confirmed that both miRNA-499 and miRNA-22 were potential candidates
      influencing DL trait by their expression pattern analysis. Overall, our data
      enhance the knowledge of porcine skeletal muscle miRNAs, and provide foundation
      for clarifying the miRNA regulatory mechanisms involved in DL trait.

PMID- 29320760
TI  - A Standard Nomenclature for Referencing and Authentication of Pluripotent Stem
      Cells.
AB  - Unambiguous cell line authentication is essential to avoid loss of association
      between data and cells. The risk for loss of references increases with the
      rapidity that new human pluripotent stem cell (hPSC) lines are generated,
      exchanged, and implemented. Ideally, a single name should be used as a generally
      applied reference for each cell line to access and unify cell-related information
      across publications, cell banks, cell registries, and databases and to ensure
      scientific reproducibility. We discuss the needs and requirements for such a
      unique identifier and implement a standard nomenclature for hPSCs, which can be
      automatically generated and registered by the human pluripotent stem cell
      registry (hPSCreg). To avoid ambiguities in PSC-line referencing, we strongly
      urge publishers to demand registration and use of the standard name when
      publishing research based on hPSC lines.

PMID- 29320761
TI  - Expandable Arterial Endothelial Precursors from Human CD34+ Cells Differ in Their
      Proclivity to Undergo an Endothelial-to-Mesenchymal Transition.
AB  - Arterial diseases continue to pose a major health concern but in vitro studies
      are limited because explanted cells can exhibit poor proliferative capacity and a
      loss of specificity. Here, we find that two transcription factors, MYCN and
      SOX17, induce and indefinitely expand in culture precursors of human arterial
      endothelial cells (expandable arterial endothelial precursors [eAEPs]). The eAEPs
      are derived from CD34+ cells found in umbilical cord blood or adult bone marrow.
      Independent eAEP lines differ in their proclivity to undergo an endothelial-to
      mesenchymal transition (EndoMT), a hallmark event in a broad array of vascular
      diseases and disorders. Some cell lines spontaneously become mesenchymal over
      time in culture, an effect exacerbated by inhibition of the fibroblast growth
      factor receptor, while others do not readily convert. These distinctions were
      exploited to identify genes that correlate with resistance to an EndoMT and to
      elucidate transcriptional changes that underpin the transition.

PMID- 29320763
TI  - A de novo 50-bp GNAS Intragenic Duplication in a Patient with
      Pseudohypoparathyroidism Type 1a.
AB  - Germline intragenic mutations in the GNAS locus result in
      pseudohypoparathyroidism type 1a (PHP1a) and related conditions. Nearly half of
      the previously reported GNAS intragenic mutations were structural variants,
      including 3 tandem duplications of 12-25 bp. However, the precise mutation
      spectrum and the genomic basis of GNAS structural variants remain to be
      clarified. Here, we report a de novo 50-bp tandem duplication in GNAS
      (c.723_772dup50, p.Glu259Leufs*29) identified in a patient with typical clinical
      features of PHP1a. The mutant transcript was predicted to undergo mRNA decay or
      encode a nonfunctional protein. The 2 breakpoints of the duplication shared a 1
      bp microhomology but were not associated with long homology or nucleotide
      stretches. We also examined the breakpoint structures of 3 previously reported
      GNAS duplications and found that 1 had a structure similar to that of our case,
      while the remaining 2 had blunt-ended breakpoints without microhomologies. In
      silico analyses revealed that the GNAS-flanking region was not enriched with
      repeats, palindromes, noncanonical DNA motifs, or GC content. This study expands
      the mutation spectrum of GNAS and provides the first indication that GNAS
      intragenic structural variants are induced by multiple processes, including
      nonhomologous end-joining and/or microhomology-mediated break-induced
      replication, independently of known rearrangement-inducing DNA features.

PMID- 29320762
TI  - Corrected and Republished from: Identification of Peptidoglycan Hydrolase
      Constructs with Synergistic Staphylolytic Activity in Cow's Milk.
AB  - Peptidoglycan hydrolases (PGHs) have been suggested as novel therapeutics for the
      treatment of bovine mastitis. However, activity in the presence of cow's milk is
      an important requirement for drugs administered into the bovine udder. We have
      used a microtiter plate-based protocol to screen a library of >170 recombinant
      PGHs, including engineered bacteriophage endolysins, for enzymes with activity
      against Staphylococcus aureus in milk. Eight suitable PGH constructs were
      identified by this approach, and their efficacies against S. aureus in heat
      treated milk were compared by time-kill assays. The two most active enzymes
      (lysostaphin and CHAPK_CWT-LST) reduced S. aureus numbers in milk to undetectable
      levels within minutes at nanomolar concentrations. Due to their different
      peptidoglycan cleavage sites, these PGH constructs revealed synergistic activity,
      as demonstrated by checkerboard assays, spot assays, and time-kill experiments.
      Furthermore, they proved active against a selection of staphylococcal mastitis
      isolates from different geographical regions when applied individually or in
      synergistic combination. The PGH combination completely eradicated S. aureus from
      milk: no more bacteria were detected within 24 h after the addition of the
      enzymes, corresponding to a reduction of >9 log units from the level in the
      control. Efficacy was also retained at different inoculum levels (3 log versus 6
      log CFU/ml) and when S. aureus was grown in milk as opposed to broth prior to the
      experiments. In raw cow's milk, CHAPK_CWT-LST showed reduced efficacy, whereas
      lysostaphin retained its activity, reducing bacterial numbers by >3.5 log units
      within 3 h.IMPORTANCE Staphylococci, and S. aureus in particular, are a major
      cause of bovine mastitis, an inflammation of the mammary gland in cows that is
      associated with high costs and risks for consumers of milk products. S. aureus
      induced mastitis, commonly treated by intramammary infusion of antibiotics, is
      characterized by low cure rates and increasing antibiotic resistance in bacteria.
      Therefore, alternative treatment options are highly desirable. PGHs, including
      bacteriophage endolysins, rapidly and specifically kill selected pathogens by
      degrading their cell walls and are refractory to resistance development; thus,
      they have promise as novel antibacterial agents. This study employed a screening
      approach to identify PGH constructs with high staphylolytic activity in cow's
      milk among a large collection of enzymes. Our results suggest that the most
      promising enzymes identified by this strategy hold potential as novel mastitis
      therapeutics and thus support their further characterization in animal models.

PMID- 29320764
TI  - Usefulness of Mean Corpuscular Volume for Detection of Advanced Colorectal Cancer
      in Patients Older than 85 Years.
AB  - BACKGROUND/AIMS: The aim of this study was to elucidate clinical indicators for
      the detection of advanced colorectal cancer (ACRC). METHODS: This was a
      retrospective study conducted at a tertiary hospital. This study included 333
      patients older than 85 years who underwent colonoscopy from April 2006 to May
      2010. The detection rate of ACRC was assessed. Then, we analyzed the association
      between the detection of ACRC and various background factors including mean
      corpuscular volume (MCV). We also analyzed the cumulative overall survival of
      patients with detected ACRC. RESULTS: ACRC was found in 37 patients, resulting in
      a detection rate of 15%. Multivariate logistic regression analysis revealed that
      a decreased MCV was an independent predictor for the detection of ACRC (OR 0.88,
      95% CI 0.84-0.94), whereas symptoms such as abdominal pain, hematochezia, or
      anemia were not independent predictors. MCV was an independent predictor
      irrespective of the location of the tumor. The cumulative survival rates at 3 and
      5 years after diagnosis were 78 and 58%, respectively, during a median
      observational period of 30.3 months. CONCLUSION: This study demonstrated the
      usefulness of MCV as an indicator of the necessity of colonoscopy for older
      patients.

PMID- 29320765
TI  - Emerging Treatment Options in Atopic Dermatitis: Systemic Therapies.
AB  - The pathogenesis of atopic dermatitis (AD) is multifactorial and intricate, and
      the clinical presentation of the condition varies greatly. Symptoms and severity
      depend on individual trigger factors and stage of the disease. The majority of AD
      patients are sufficiently treated with emollients in combination with existing
      topical or systemic therapies. Yet treatment failure with existing drugs and
      treatment options can be a significant clinical problem. New treatments are under
      development, and the majority of these new drugs focus on targeting a skewed
      immune response in AD. Novel therapeutic approaches, which target the pathways
      involved in the pathogenesis of AD, may provide a potentially more effective and
      less harmful approach to systemic therapy. These pharmaceutical agents are
      designed to narrowly modify or directly block a specific cellular signal or pro
      inflammatory pathway. We review systemic drugs in the pipeline for AD. To make
      the review as current and pertinent as possible, we selected to focus on AD
      related therapies available in the clinicaltrials.gov database with a first
      received date after January 1, 2014, up until May 31, 2017. We excluded therapies
      that could be categorized as either traditional Chinese medicine, herbal
      medicine, probiotics, histamine/leukotriene blockers, immuno-adsorption, or
      immunostimulants.

PMID- 29320767
TI  - Ecological Approaches to Dental Caries Prevention: Paradigm Shift or Shibboleth?
AB  - Contemporary paradigms of dental caries aetiology focus on the ecology of the
      dental plaque biofilm and how local environmental factors can modulate this to
      cause disease. The crucial role that a healthy oral microbiome plays in
      preventing caries and promoting oral health is also being increasingly
      recognized. Based on these concepts, several ecological preventive approaches
      have been developed that could potentially broaden the arsenal of currently
      available caries-preventive measures. Many of these ecological approaches aim for
      long-term caries control by either disrupting cariogenic virulence factors
      without affecting bacterial viability, or include measures that can enhance the
      growth of health-associated, microbially diverse communities in the oral
      microbiome. This paper argues for the need to develop ecological preventive
      measures that go beyond conventional caries-preventive methods, and discusses
      whether these ecological approaches can be effective in reducing the severity of
      caries by promoting stable, health-associated oral biofilm communities.

PMID- 29320766
TI  - Improved Visibility of Barrett's Esophagus with Linked Color Imaging: Inter- and
      Intra-Rater Reliability and Quantitative Analysis.
AB  - BACKGROUND/AIMS: To evaluate the usefulness of linked color imaging (LCI) and
      blue LASER imaging (BLI) in Barrett's esophagus (BE) compared with white light
      imaging (WLI). METHODS: Five expert and trainee endoscopists compared WLI, LCI,
      and BLI images obtained from 63 patients with short-segment BE. Physicians
      assessed visibility as follows: 5 (improved), 4 (somewhat improved), 3
      (equivalent), 2 (somewhat decreased), and one (decreased). Scores were evaluated
      to assess visibility. The inter- and intra-rater reliability (intra-class
      correlation coefficient) of image assessments were also evaluated. Images were
      objectively evaluated based on L* a* b* color values and color differences
      (DeltaE*) in a CIELAB color space system. RESULTS: Improved visibility compared
      with WLI was achieved for LCI: 44.4%, BLI: 0% for all endoscopists; LCI: 55.6%,
      BLI: 1.6% for trainees; and LCI: 47.6%, BLI: 0% for experts. The visibility score
      of trainees compared with experts was significantly higher for LCI (p = 0.02).
      Intra- and inter-rater reliability ratings for LCI compared with WLI were
      "moderate" for trainees, and "moderate-substantial" for experts. The DeltaE*
      revealed statistically significant differences between WLI and LCI. CONCLUSION:
      LCI improved the visibility of short-segment BE compared with WLI, especially for
      trainees, when evaluated both subjectively and objectively.

PMID- 29320768
TI  - Attention Deficit Hyperactivity Disorder Symptoms are Common in Patients in
      Opioid Maintenance Treatment.
AB  - INTRODUCTION AND AIMS: Knowledge of attention deficit hyperactivity disorder
      (ADHD) symptoms among patients in opioid maintenance treatment (OMT) is important
      for treatment optimization and yet limited. We investigated the prevalence of
      ADHD symptoms, and factors associated with high ADHD symptom burden in a group of
      Norwegian OMT patients. METHODS: We interviewed individuals entering OMT across
      Norway in 2 steps between 2012 and 2016. ADHD symptoms were measured by the Adult
      ADHD Self-Report Scale (ASRS; n = 175). We compared 2 groups of individuals who
      scored above or below the clinical cutoff score. Mental distress was measured
      with the General Symptom Index (GSI) of the Hopkin's Symptom Check-List-25.
      RESULTS: A total of 33% of the OMT patients screened positively for ADHD on the
      ASRS. Participants who scored above the clinical cutoff were younger, and
      reported more severe substance use and mental distress. When controlling for
      other significant variables in a logistic regression analysis, scoring above
      cutoff on the ASRS was associated with higher GSI (OR 1.61; 95% CI 1.03-2.50) and
      use of stimulants (OR 2.55; 1.13-5.76). CONCLUSIONS: ADHD symptoms were common in
      these OMT patients. High ADHD symptom burden was associated with higher mental
      distress and use of stimulants. This underlines a need of more systematic focus
      on ADHD in OMT to plan treatment accordingly.

PMID- 29320769
TI  - Electronic Nose in the Detection of Wound Infection Bacteria from Bacterial
      Cultures: A Proof-of-Principle Study.
AB  - BACKGROUND: Soft tissue infections, including postoperative wound infections,
      result in a significant burden for modern society. Rapid diagnosis of wound
      infections is based on bacterial stains, cultures, and polymerase chain reaction
      assays, and the results are available earliest after several hours, but more
      often not until days after. Therefore, antibiotic treatment is often administered
      empirically without a specific diagnosis. METHODS: We employed our electronic
      nose (eNose) system for this proof-of-concept study, aiming to differentiate the
      most relevant bacteria causing wound infections utilizing a set of clinical
      bacterial cultures on identical blood culture dishes, and established bacterial
      lines from the gaseous headspace. RESULTS: Our eNose system was capable of
      differentiating both methicillin-sensitive Staphylococcus aureus (MSSA) and
      methicillin-resistant Staphylococcus aureus (MRSA), Streptococcus pyogenes,
      Escherichia coli, Pseudomonas aeruginosa, and Clostridium perfringens with an
      accuracy of 78% within minutes without prior sample preparation. Most
      importantly, the system was capable of differentiating MRSA from MSSA with a
      sensitivity of 83%, a specificity of 100%, and an overall accuracy of 91%.
      CONCLUSIONS: Our results support the concept of rapid detection of the most
      relevant bacteria causing wound infections and ultimately differentiating MRSA
      from MSSA utilizing gaseous headspace sampling with an eNose.

PMID- 29320770
TI  - Long-Term Survivor Characteristics in Hemodialysis Patients with Type 2 Diabetes.
AB  - BACKGROUND: Data concerning long-term mortality predictors among large, purely
      diabetic hemodialysis collectives are scarce. METHODS: We used data from a
      multicenter, prospective, randomized trial among 1,255 hemodialysis patients with
      type 2 diabetes mellitus (T2DM) and its observational follow-up study. The
      association of 10 baseline candidate variables with mortality was assessed by Cox
      proportional hazards regression. RESULTS: Overall, 103 participants survived the
      median follow-up of 11.5 years. Significant predictors of mortality were age
      (hazard ratio [HR] 1.03, 95% CI 1.02-1.04), cardiovascular (HR 1.42, 95% CI 1.25
      1.62) and peripheral vascular disease (HR 1.55, 95% CI 1.36-1.76), higher
      hemoglobin A1c (HbA1c; HR 1.08, 95% CI 1.03-1.14), and loss of self-dependency
      (HR 1.20, 95% CI 1.03-1.39). Higher albumin (HR 0.72, 95% CI 0.59-0.89) and body
      mass index (BMI; HR 0.98, 95% CI 0.96-0.99) had protective associations. There
      was no significant association with sex, diabetes duration, and cerebrovascular
      diseases. Subgroup analyses by age and diabetes duration showed stronger
      associations of cardiovascular disease, HbA1c, albumin, BMI, and loss of self
      dependency in younger patients and/or shorter diabetes duration. Loss of self
      dependency and energy resources (albumin, BMI) increased mortality more severely
      in women, whilst the impact of cardiovascular and peripheral vascular diseases
      was more pronounced in men. CONCLUSION: Long-term mortality risk in patients with
      T2DM on hemodialysis was associated with higher age, vascular diseases, HbA1c,
      loss of self-dependency, and low energy resources. Interestingly, it does not
      vary between sexes. Further individualized prognosis estimation and therapy
      should strongly depend on age, diabetes duration, and gender.

PMID- 29320771
TI  - Perianal Infections in the Phase before Engraftment after Allogeneic
      Hematopoietic Stem Cell Transplantations: A Study of the Incidence, Risk Factors,
      and Clinical Outcomes.
AB  - In this study, we aimed to investigate the incidence, risk factors, and clinical
      outcomes of perianal infections during the pre-engraftment phase after allogeneic
      hematopoietic stem cell transplantation (allo-HSCT). Consecutive patients who
      underwent non-T-cell-depleted allo-HSCT at the Peking University Institute of
      Hematology from January 1 to December 31, 2016 were enrolled (n = 646). Ninety
      nine patients were found to have perianal infections during the pre-engraftment
      phase, and 80 were found to have neutropenia on perianal infection diagnosis. The
      cumulative incidence of perianal infection during the pre-engraftment phase after
      allo-HSCT was 15.3%. A history of perianal infection (hazard ratio [HR] = 15.28,
      p < 0.001) or hemorrhoids before allo-HSCT (HR = 3.09, p = 0.001) was
      significantly associated with the new occurrence of perianal infection after allo
      HSCT. All patients received empirical broad-spectrum antimicrobial therapies, and
      97 were cured after treatment. The clinical outcomes at 100 days after allo-HSCT
      were comparable in patients with and without perianal infections. In summary,
      patients who had perianal infection or hemorrhoids before allo-HSCT had a higher
      risk of new occurrence of perianal infection after allo-HSCT. With appropriate
      treatment, perianal infection during the pre-engraftment phase did not influence
      the clinical outcomes.

PMID- 29320772
TI  - A Perfect sTORm: The Role of the Mammalian Target of Rapamycin (mTOR) in
      Cerebrovascular Dysfunction of Alzheimer's Disease: A Mini-Review.
AB  - Cerebrovascular dysfunction is detected prior to the onset of cognitive and
      histopathological changes in Alzheimer's disease (AD). Increasing evidence
      indicates a critical role of cerebrovascular dysfunction in the initiation and
      progression of AD. Recent studies identified the mechanistic/mammalian target of
      rapamycin (mTOR) as a critical effector of cerebrovascular dysfunction in AD.
      mTOR has a key role in the regulation of metabolism, but some mTOR-dependent
      mechanisms are uniquely specific to the regulation of cerebrovascular function.
      These include the regulation of cerebral blood flow, blood-brain barrier
      integrity and maintenance, neurovascular coupling, and cerebrovascular
      reactivity. This article examines the available evidence for a role of mTOR
      driven cerebrovascular dysfunction in the pathogenesis of AD and of vascular
      cognitive impairment and dementia (VCID) and highlights the therapeutic potential
      of targeting mTOR and/or specific downstream effectors for vasculoprotection in
      AD, VCID, and other age-associated neurological diseases with cerebrovascular
      etiology.

PMID- 29320773
TI  - Association between Antioxidant Enzyme Activities and Enterovirus-Infected Type 1
      Diabetic Children.
AB  - OBJECTIVE: To examine the effect of infection with Enterovirus (EV) in children
      with type 1 diabetes (T1D) on the activities of serum antioxidant enzymes in
      diabetic and nondiabetic controls. SUBJECTS AND METHODS: Three hundred and eighty
      two diabetic and 100 nondiabetic children were tested for EV RNA using reverse
      transcriptase (RT)-PCR. The activities of serum superoxide dismutase (SOD),
      glutathione peroxidase (GPx), and catalase (CAT) were also estimated in diabetic
      patients infected with EV (T1D-EV+), those not infected with EV (T1D-EV-), and in
      nondiabetic controls. RESULTS: The frequency of EV was higher in diabetic
      children (100/382; 26.2%) than in healthy controls (0/100). Levels of fasting
      blood glucose (FBG), glycosylated hemoglobin (HbA1c) and C-reactive protein (CRP)
      were significantly higher but C-peptide was significantly lower in diabetic
      children than in controls. CRP levels were higher in the T1D-EV+ group than in
      the T1D-EV- group, and higher in all diabetic children than in nondiabetic
      controls. The activities of the antioxidant enzymes GPx, SOD, and CAT decreased
      significantly in diabetic children compared to in controls. Moreover, the
      activities of the enzymes tested were significantly reduced in the T1D-EV+ group
      compared to in the T1D-EV- group. CONCLUSION: Our data indicate that EV infection
      correlated with a decrease in the activity of antioxidant enzymes in the T1D-EV+
      group compared to in the T1D-EV- group; this may contribute to beta cell damage
      and increased inflammation.

PMID- 29320774
TI  - How Many Passes Are Needed for Endobronchial Ultrasound-Guided Transbronchial
      Needle Aspiration for Sarcoidosis? A Prospective Multicenter Study.
AB  - BACKGROUND: While endobronchial ultrasound-guided transbronchial needle
      aspiration (EBUS-TBNA) is widely used as an initial diagnostic procedure for
      pathological confirmation of sarcoidosis, it is unclear how many passes are
      required to obtain diagnostic materials. OBJECTIVES: The aim of this study was to
      determine the number of needle passes needed for the diagnosis of stage I/II
      sarcoidosis using EBUS-TBNA. METHODS: At three institutions, 109 patients with
      suspected stage I/II sarcoidosis were recruited and underwent 6 passes of EBUS
      TBNA for the main target lesion. Additional EBUS-TBNA for other lesions was
      permitted. The cumulative yields of needle passes for detecting noncaseating
      epithelioid cell granulomas were analyzed. RESULTS: A total of 109 patients
      underwent EBUS-TBNA for 184 lesions. EBUS-TBNA identified specimens containing
      granulomas in 81 of 92 patients (88%) with a final diagnosis of sarcoidosis. The
      cumulative yields through the first, second, third, fourth, fifth, and sixth
      passes for the main target lesion were 63, 75, 82, 85, 86 and 88%, respectively.
      In the 55 patients that underwent EBUS-TBNA for multiple lesions, the cumulative
      yields of 2 passes per lesion for 2 lesions (total of 4 passes) and of 4 passes
      for single lesions were 86 and 84%, respectively (p = 1.00). CONCLUSIONS: If
      rapid on-site cytological evaluation is not available, we recommend at least 4
      passes per patient for either single or multiple lesions with EBUS-TBNA for
      pathological diagnosis of stage I/II sarcoidosis.

PMID- 29320775
TI  - Cholestatic Jaundice as a Paraneoplastic Manifestation of Prostate Cancer
      Aggravated by Steroid Therapy.
AB  - OBJECTIVE: To report a rare case of paraneoplastic jaundice as a manifestation of
      prostate cancer. CLINICAL PRESENTATION AND INTERVENTION: We report on a case of
      paraneoplastic syndrome in a 72-year-old man with prostate cancer that manifested
      with idiopathic jaundice. Although steroids can be used as treatment in patients
      with prostate cancer, they could exacerbate paraneoplastic jaundice. The jaundice
      that flared up after treatment with 40 mg prednisone was improved with
      antiandrogen treatment. CONCLUSION: Physicians should be aware of the possibility
      of paraneoplastic jaundice in patients with prostate cancer. Appropriate
      antiandrogen therapy should be considered for paraneoplastic jaundice in these
      patients.

PMID- 29320776
TI  - V600E BRAF versus Non-V600E BRAF Mutated Lung Adenocarcinomas: Cytomorphology,
      Histology, Coexistence of Other Driver Mutations and Patient Characteristics.
AB  - OBJECTIVES: We analyzed the morphologic features and clinical characteristics of
      lung adenocarcinomas (ACAs) harboring mutated BRAF. STUDY DESIGN: A review of the
      histology/cytology of BRAF-mutated lung ACAs was performed at the Johns Hopkins
      Hospital from January 1, 2013, to January 1, 2015. Patient demographics, clinical
      history, and ACA morphology were assessed. RESULTS: Thirty-six cases were
      identified with a median age of 66 years (range 44-87), 58% (21/36) were female,
      and 94% (34/36) were current or former smokers. In total, 28% (10/36) had a BRAF
      V600E mutation. Concurrent mutations were identified in KRAS in 4 cases (11%),
      PIK3CA in 2 cases (6%), and AKT1 in 2 cases (6%). No cases tested for ALK
      rearrangement were positive. The tumor grading varied from well to poorly
      differentiated, and the architecture assumed various patterns, including
      papillary, micropapillary, solid/cribriform, lepidic, and acinar. Of the cases
      with immunostains, 90% (18/20) were TTF-1 positive, 88% (14/16) were napsin-A
      positive, and 100% (8/8) were P63 negative. CONCLUSION: Mutated-BRAF lung ACA
      arose on average in the seventh decade of life in patients who were current or
      former smokers and was infrequently found in combination with other common lung
      ACA driver mutations. The actionable V600E mutation was present in <30% of cases,
      more commonly in females. The histologic grade and architecture of these tumors
      varied significantly.

PMID- 29320777
TI  - A Case of Giant Supratentorial Choroid Plexus Carcinoma in a Young Girl.

PMID- 29320778
TI  - Five-Year Recurrence Rate and the Predictors Following Stroke in the Mashhad
      Stroke Incidence Study: A Population-Based Cohort Study of Stroke in the Middle
      East.
AB  - BACKGROUND: Little is known about the risk of recurrent stroke in low- and middle
      income countries. This study was designed to identify the long-term risk of
      stroke recurrence and its associated factors. METHODS: From November 21, 2006 for
      a period of 1 year, 624 patients with first-ever stroke (FES) were registered
      from the residents of 3 neighborhoods in Mashhad, Iran. Patients were followed up
      for the next 5 years after the index event for any stroke recurrence or death. We
      used competing risk analysis and cause-specific Cox proportional hazard models to
      estimate the cumulative incidence of stroke recurrence and its associated
      variables. RESULTS: The cumulative incidence of stroke recurrence was 14.5% by
      the end of 5 years, with the largest rate during the first year after FES (5.6%).
      Only advanced age (adjusted hazard ratio [HR] 1.02; 95% CI 1.01-1.04) and severe
      stroke (National Institutes of Health Stroke Scale score >20; HR 2.23; 95% CI
      1.05-4.74) were independently associated with an increased risk of 5-year
      recurrence. Case fatality at 30 days after first recurrent stroke was 43.2%,
      which was significantly greater than the case fatality at 30 days after FES of
      24.7% (p = 0.001). CONCLUSION: A substantial number of our patients either died
      or had stroke recurrences during the study period. Advanced age and the severity
      of the index stroke significantly increased the risk of recurrence. This is an
      important finding for health policy makers and for designing preventive
      strategies in people surviving their stroke.

PMID- 29320779
TI  - Prognostic Factors for Survival among Patients with Small Bowel Neuroendocrine
      Tumours Associated with Mesenteric Desmoplasia.
AB  - BACKGROUND: Small intestinal neuroendocrine tumours (SI NETs) represent 30-50% of
      small bowel neoplasms and are often associated with diverse fibrotic
      complications. Mesenteric fibrosis is a hallmark of SI NETs which may cause
      substantial morbidity and is considered an adverse feature. However, survival
      analyses in this group of patients are lacking. METHODS: The aim of this
      retrospective study was to determine the overall survival (OS) and factors
      affecting prognosis in a large cohort of 147 patients with SI NETs and
      radiological evidence of mesenteric desmoplasia from our centre. The severity of
      desmoplasia was graded radiologically and its effect on OS and long-term
      complications was assessed. The median follow-up period was 82 months. RESULTS:
      The median OS was 8.7 years (95% CI 6.8-9.9) with an overall 5-year survival of
      71%. The univariate analysis demonstrated that an age >65 years, a liver tumour
      burden >50% of the hepatic parenchyma, carcinoid heart disease, chromogranin A
      levels >10 times the upper limit of normal, and urinary 5-hydroxyindoleacetic
      acid (5-HIAA) levels >5 times the upper limit of normal were poor
      prognosticators, while primary resection was associated with a longer OS.
      However, only an age >65 years and urinary 5-HIAA levels >10 times the upper
      limit of normal remained statistically significant after multivariate analysis.
      The severity of mesenteric desmoplasia did not seem to demonstrate a
      statistically significant relationship to OS or long-term outcomes. CONCLUSION:
      This study is the first comprehensive survival analysis of patients with SI NETs
      associated with mesenteric desmoplasia and has provided important and clinically
      relevant epidemiological data for this group of patients.

PMID- 29320780
TI  - The Evolution of Neuroendocrine Tumor Treatment Reflected by ENETS Guidelines.
AB  - In 2016, the third version of guidelines for the diagnosis and treatment of
      neuroendocrine tumors (NETs) has been published by the European Neuroendocrine
      Tumor Society (ENETS). These guidelines reflect the progress in treatment of
      NETs, and by comparing the newest guidelines with the first guidelines of 2001,
      this progress can be clearly recognized. Diagnostic accuracy has been increased
      by the introduction of PET-CT with Ga-labelled somatostatin analogs, and multiple
      new treatments and treatment schedules have been developed, like peptide receptor
      radiotherapy with radiolabeled somatostatin analogs, or targeted therapies.
      Evidence and indications for these therapies are discussed in the ENETS
      guidelines. In this review, we aim to show the progress in NET diagnosis and
      treatment on the basis of the advances in the guidelines, but also to discuss the
      unsolved questions and unmet needs which still remain.

PMID- 29320781
TI  - The Draft Genome Assembly of Dermatophagoides pteronyssinus Supports
      Identification of Novel Allergen Isoforms in Dermatophagoides Species.

PMID- 29320782
TI  - Thyroid Hormone Status in Overweight Children with Attention
      Deficit/Hyperactivity Disorder.
AB  - BACKGROUND: There is an ongoing discussion whether thyroid hormones are involved
      in the development and course of attention deficit/hyperactivity disorder (ADHD).
      Since obesity is associated with both higher thyroid-stimulating hormone (TSH)
      and free triiodothyronine (fT3) concentrations and increased rates of ADHD, we
      hypothesized that overweight children with ADHD show higher TSH and fT3
      concentrations compared to overweight children without ADHD. METHODS: TSH, fT3,
      fT4, and leptin levels were analyzed in 230 children (60.9% boys, 9.3 +/- 1.7
      years old, 35.7% migration background). The children were divided into four
      groups (I = 26 overweight children with ADHD, II = 56 normal-weight children with
      ADHD, III = 66 overweight children without ADHD, and IV = 82 normal-weight
      children without ADHD). Severity of ADHD was determined by the parent version of
      the Connors 3(r) rating scales. RESULTS: Overweight children with ADHD did not
      differ significantly from overweight children without ADHD with respect to TSH,
      fT3, or fT4 concentrations. Comparing the thyroid hormones between the four
      groups also demonstrated no significant differences for TSH and fT4
      concentrations. fT3 concentrations were significantly higher in normal-weight
      children with ADHD compared to normal-weight children without ADHD. Inattention
      and hyperactivity/impulsivity scores were not significantly related to TSH or fT3
      in multiple regression analyses adjusted for age, gender, and migration
      background. In these analyses, TSH was associated with BMI SDS (beta coefficient
      0.19 +/- 0.12, p = 0.002) and leptin (exp[beta coefficient] 1.87 +/- 1.36, p <
      0.001). fT3 (beta coefficient 0.06 +/- 0.05, p = 0.009) and leptin (exp[beta
      coefficient] 1.17 +/- 1.13, p = 0.009) were also associated with BMI SDS.
      CONCLUSIONS: Our findings confirm the relation between overweight and thyroid
      hormones but point against the hypothesis that thyroid hormones might link
      overweight and ADHD in children.

PMID- 29320784
TI  - Going Fishing.

PMID- 29320783
TI  - WT1 Gene Mutation, p.R462W, in a 46,XY DSD Patient from Egypt with Gonadoblastoma
      and Review of the Literature.
AB  - WT1 gene mutations have been described in 46,XY patients with ambiguous genitalia
      or complete gonadal dysgenesis with or without Wilms' tumor, nephropathy,
      gonadoblastoma, and other defects, e.g., cryptorchidism or hypospadias. p.R462W
      is a hot spot mutation in exon 9 and is the most common mutation in patients with
      Denys-Drash syndrome. However, in this study we report an Egyptian patient with a
      novel phenotype carrying the p.R462W mutation. We also review the heterogeneity
      of phenotypes of previously reported patients with the p.R462W (previously
      referred to as Arg394Trp) mutation.

PMID- 29320785
TI  - [Neck swelling - a surprising diagnosis].

PMID- 29320786
TI  - Imaging of Ligamentous Structures within the Knee Includes Much More Than the
      ACL.
AB  - Ligamentous structures of the knee are numerous and complex, including the
      anterior and posterior cruciate ligaments, medial and lateral collateral
      ligaments, ligaments of the posteromedial and posterolateral corners, and the
      anterolateral ligament. Clinical assessment after a knee injury is paramount and
      can direct both the clinician's choice of imaging study and the radiologist's
      interpretation. Imaging is crucial in that it provides additional information for
      diagnosis, management, and surgical planning. Multiple imaging modalities can be
      used in the evaluation of the knee injuries, with radiographs an important
      baseline study, magnetic resonance imaging as the best tool for a comprehensive
      assessment including cruciate ligament evaluation, and ultrasound useful in
      evaluating superficial structures. Knowledge of both normal and pathological
      appearances of ligamentous structures, as well as typical injury patterns, is
      useful not only for radiologists but also for clinicians who manage patients with
      knee pain.

PMID- 29320787
TI  - ?

PMID- 29320788
TI  - [Competence-based Training in the "Protected Environment": From Sheltered Space
      to Real Life].
AB  - The idea of "learning in a protected environment" is frequently used within the
      framework of postgradual education in anaesthesiology. However it remains unclear
      and its exact meaning lies in the eye of the beholder. This paper aims to
      highlight the definition of the term "protected environment" and its relevance in
      anaesthesiology. This includes teaching and learning strategies like competence
      based training and simulation based training in all its variations. We conclude
      with an attempt to classify the wide variety of Simulators and teaching methods
      in use including their individual problems transferred into real life situations.
      Concerning the fact that this paper is supposed to be a review in medical
      education, its structure differs from case related papers with more medical
      content.

PMID- 29320789
TI  - [Simulation as a Training Method for the Professionalization of Teams].
AB  - Simulation as an educational method can be applied to the training of processes,
      technical and non-technical skills. This article focuses on the role of
      simulation in crisis resource management and non-technical skills. A realistic
      work environment requires well-trained staff regarding simulation technology and
      communication. A training (unit) is divided into three sections. During the
      briefing the team is introduced to the scenario. Afterwards, the patient is
      treated by an interdisciplinary team. Communication under the pressure of action,
      even if one does not agree with the approach of the colleagues, should be
      practiced. After the scenario a structured debriefing is conducted. The trainer
      supervises the reflection of the teams' actions. Various methods such as "guided
      team self-correction", "advocacy-inquiry" and the "TeamGAINS"-approach are
      available for this decisive phase of the training. A safe environment is
      guaranteed, video recordings will never leave the training. Active
      experimentation, concrete experiences and accurate reflection are the key factors
      of success for the method simulation. Positive effects on critical incidents,
      resuscitation outcome and improvement of team climate can be observed after
      simulation training.

PMID- 29320790
TI  - ["Learning in Protected Environment"- Implementation in Continuing Medical
      Education].
AB  - Actual concepts in continuing medical education in acute or emergency medicine
      contain skill training as well as simulation training. Methods and mechanisms to
      reduce crisis, like human factor training, shared mental models or closed-loop
      communication are incorporated. It is unknown which training method is optimal
      for individual departments in hospitals or for the individual level of education
      of the healthcare provider. A concept we provide is the so called "learning in
      protected environment": this environment protects the course participants and our
      patients from negative consequences of a conventional hands-on training.
      Concurrently the participants benefit from our standardized course concepts. We
      achieve our goal of an optimal preparation for clinical practice by continuous re
      evaluation of the content and educational objects. The implementation of a
      multimodal team training has to be adopted for each institution individually -
      methods for an implementation should be standardized. We suggest the use of the
      "Kern cycle" for a structured approach to curriculum development. On this
      foundation the combination of "learning in protected environment" and crisis
      training is optimal to achieve an improved patient safety in acute care.

PMID- 29320791
TI  - [What to Do When a Child Is Choking?]
AB  - Both ingestion and aspiration of foreign bodies are common events in children. If
      a child had something in his mouth and thereafter respiratory or swallowing
      complaints occur, both aspiration and ingestion are possible causes. Both events
      can be immediately life threatening or, if a direct threat is absent, cause
      significant long-term impairments for the children. Therefore, the identification
      of any possible threat is essential. This paper identifies the diagnostic and
      therapeutic options and needs that will ensure the best possible safety and the
      least possible consequential harm.

PMID- 29320792
TI  - [Advance Care Planning and its Relevance for Emergency and Intensive Care
      Medicine].
AB  - Like in other countries, advance care planning (ACP) is currently being
      implemented in Germany as a new concept to realise valid and effective advance
      directives. This concept comprises processes to explore and document individual
      preferences for future treatment, and to honour them at a time when the person is
      incapacitated. ACP aims to ensure that patients will be treated according to
      their preferences when they are no longer capable due to acute health crises or
      chronic diseases. This paper gives an overview of the concept of ACP with a focus
      on relevant issues for emergency and intensive care medicine.

PMID- 29320793
TI  - ?

PMID- 29320794
TI  - Assessment of Plasma Sample Quality on Siemens Atellica COAG 360 System.

PMID- 29320795
TI  - Direct Oral Anticoagulants in End-Stage Renal Disease.
AB  - Patients with end-stage renal disease (ESRD) were excluded from pivotal clinical
      trials with oral anticoagulants. While such patients are at an increased risk of
      venous and arterial thromboembolism, their risk of bleeding is also elevated. It
      is thus of little surprise that stroke prevention with vitamin K antagonists
      (VKAs) in ESRD patients with atrial fibrillation is controversial, with
      observational evidence ranging from beneficial to harmful. This uncertainty
      extends to the less studied use of VKAs for venous thromboembolism in ESRD. The
      direct oral anticoagulants (DOACs) apixaban and rivaroxaban have now permissive
      labeling in the United States for atrial fibrillation in patients with ESRD; this
      expanded labeling has not yet occurred either in Europe or for venous
      thromboembolism. This review summarizes the current evidence for the pharmacology
      of DOACs in ESRD as well as their utilization and safety in patients with ESRD
      and atrial fibrillation.

PMID- 29320796
TI  - Prevalence and Risk Factors of Acute Pulmonary Embolism in Patients with Lung
      Cancer Surgery.
AB  - Acute pulmonary embolism (PE) is one of the serious complications with high
      mortality after thoracic surgery. The authors aimed to determine the prevalence
      of PE events and evaluate additional risk factors for PE in patients with lung
      cancer surgery. Patients underwent lung cancer resections during January 2012 to
      July 2015 and had 30-day postoperative follow-up were included. Those with
      incomplete or miscoded data were excluded. The number of postoperative PE events
      was recorded retrospectively. Analyses were used to evaluate risk factors of PE
      during the hospitalization. The authors reviewed 11,474 patients who underwent
      surgery for lung cancer. The overall 30-day incidence of PE after thoracic
      surgery at their institution was 0.53%. The 30-day PE incidence without chemical
      prophylaxis was 0.57% (55/9,726) and the mortality rate was 10%. Multivariate
      analyses revealed that age over 66 (odds ratio [OR]: 1.09, 95% confidence
      interval [CI]: 1.05-1.12, p < 0.001), more extensive surgery than lobectomy (OR:
      2.34, 95% CI: 1.28-4.25, p = 0.006) and stage IV of lung cancer (OR: 4.22, 95%
      CI: 1.50-11.9, p = 0.007) were associated with an increased risk of PE. Using
      these additional risk factors, based on readily available clinical
      characteristics, can help to risk-stratify patients and warrant extended chemical
      prophylaxis for patients to reduce the incidence of acute PE.

PMID- 29320798
TI  - Incorrectly Performed Meaningful Use Audits Hurt Small Practices.

PMID- 29320797
TI  - Measuring Electronic Health Record Use in Primary Care: A Scoping Review.
AB  - BACKGROUND: Simple measures of electronic health record (EHR) adoption may be
      inadequate to evaluate EHR use; and positive outcomes associated with EHRs may be
      better gauged when varying degrees of EHR use are taken into account. In this
      article, we aim to assess the current state of the literature regarding measuring
      EHR use. OBJECTIVE: This article conducts a scoping review of the literature to
      identify and classify measures of primary care EHR use with a focus on the
      Canadian context. METHODS: We conducted a scoping review. Multiple citation
      databases were searched, as well as gray literature from relevant Web sites.
      Resulting abstracts were screened for inclusion. Included full texts were
      reviewed by two authors. Data from the articles were extracted; we synthesized
      the findings. Subsequently, we reviewed these results with seven EHR stakeholders
      in Canada. RESULTS: Thirty-seven articles were included. Eighteen measured EHR
      function use individually, while 19 incorporated an overall level of use. Eight
      frameworks for characterizing overall EHR use were identified. CONCLUSION: There
      is a need to create standardized frameworks for assessing EHR use.

PMID- 29320799
TI  - New Phenylethanoid Glycosides from Cistanche phelypaea and Their Activity as
      Inhibitors of Monoacylglycerol Lipase (MAGL).
AB  - Four new phenylethanoid glycosides (1: -4: ), 1-beta-p-hydroxyphenyl-ethyl-2-O
      acetyl-3,6-di-alpha-l-rhamnopyranosyl-beta-d-glucopyranoside (1: ), 1-beta-p
      hydroxyphenyl-ethyl-3,6-O-di-alpha-l-rhamnopyranosyl-beta-d-glucopyranoside (2:
      ), 1-beta-p-hydroxyphenyl-ethyl-2-O-acetyl-3,6-di-alpha-l-rhamnopyranosyl-4-p
      coumaroyl-beta-d-glucopyranoside (3: ), and 1-beta-p-hydroxyphenyl-ethyl-3,6-di
      alpha-l-rhamnopyranosyl-4-p-coumaroyl-beta-d-glucopyranoside (4: ), together with
      three known compounds, were isolated from the n-butanol extract of Cistanche
      phelypaea aerial parts. The structural characterization of all compounds was
      performed by spectroscopic analyses, including 1D and 2D NMR, and HRESIMS
      experiments. The isolated compounds were assayed for their inhibitory activity on
      two enzymes involved in the peculiar glycolytic or lipidic metabolism of cancer
      cells, human lactate dehydrogenase (LDH), and monoacylglycerol lipase (MAGL),
      respectively. All the compounds showed negligible activity on LDH, whereas some
      of them displayed a certain inhibition activity on MAGL. In particular, compound
      1: was the most active on MAGL, showing an IC50 value of 88.0 uM, and modeling
      studies rationalized the supposed binding mode of 1: in the MAGL active site.

PMID- 29320800
TI  - Risks of Preterm Premature Rupture of Membranes and Preterm Birth Post Fetoscopy
      Based on Location of Trocar Insertion Site.
AB  - OBJECTIVE:  The objective of this study was to assess whether the location of the
      trocar insertion site for laser treatment of twin-twin transfusion syndrome was
      associated with preterm-premature rupture of membranes (PPROM) and preterm birth
      (PTB). STUDY DESIGN:  In this study trocar location was documented in the
      operating room. Lower uterine segment (LUS) location was defined as any insertion
      <10 cm vertically from the pubic symphysis. Lateral location was defined as >=5
      cm horizontally from the midline. Patient characteristics were tested against
      three outcomes: PPROM <= 21 days postoperative, PTB < 28 weeks, and PTB < 32
      weeks. For each outcome, multiple logistic models were fitted to examine the
      effect of trocar location, controlling for potential risk factors. RESULTS:  A
      total of 743 patients were studied. Patients with LUS location were twice as
      likely as those with a more superior location to have PPROM <= 21 days (OR =
      2.33, 1.12-4.83, p = 0.0236). Patients with both a LUS and Lateral location were
      over six times more likely to have PPROM <= 21 days (OR = 6.66, 2.36-18.78, p =
      0.0003). Trocar insertion site was not associated with PTB. CONCLUSION:  We found
      that trocar insertion in the LUS, particularly the lateral LUS, was associated
      with an increased risk of PPROM.

PMID- 29320801
TI  - Fatigue during Chest Compression Using a Neonatal Patient Simulator.
AB  - OBJECTIVE:  The objective of this study was to evaluate chest compression (CC)
      quality and operator fatigue during CC, with coordinated ventilation, on a
      neonatal simulator and to explore its association with provider aerobic activity
      and body mass index. METHODS:  This was a prospective observational experimental
      study on pediatricians, neonatologists, and neonatal nurses who frequently
      deliver newborns and who have signed the informed consent. Subjects performed CC
      coordinated with ventilations at a ratio of 3:1 for 10 minutes on a neonatal
      mannequin. Proxy of fatigue was defined as four consecutive CC below target.
      RESULTS:  Forty subjects participated; 62% were women. Twenty one (52%) evidenced
      weariness, as they performed. No gender-based differences were found in
      weariness. No subject abandoned the procedure due to fatigue. Subjects who
      participated in aerobic exercise had a significantly better performance than
      those who did not participate. Early fatigue was significantly associated with
      higher BMI. The reduction in effectiveness occurred at a mean time of 7.7 minutes
      (range 3.5-9 minutes). CONCLUSION:  CC performance quality decreased and fatigue
      was frequent before 10 minutes had elapsed on a neonatal simulator. Provider
      fatigue was associated with both lack of aerobic activity and BMI >= 25. Our
      findings support the need for guidelines requiring frequent rotation of CC
      providers during prolonged neonatal resuscitation.

PMID- 29320802
TI  - Effect of Maternal Body Mass Index and Amniotic Fluid Index on the Accuracy of
      Sonographic Estimation of Fetal Weight in Late Gestation.
AB  - OBJECTIVE:  The objective of this study was to determine the effect, if any, of
      maternal body mass index (BMI) and amniotic fluid index (AFI) on the accuracy of
      sonographic estimated fetal weight (EFW) at 40 to 42 weeks' gestation. METHODS: 
      This was a retrospective cohort study of singleton gestations with ultrasound
      performed at 40 to 42 weeks from 2010 to 2013. In this study, patients with
      documented BMI and sonographic EFW and AFI, concurrently, within 7 days of
      delivery were included. Chronic medical conditions and fetal anomalies were
      excluded from this study. The primary variable of interest was the rate of
      substantial error in EFW, defined as absolute percentage error (APE) >10%.
      RESULTS:  A total of 1,000 pregnancies were included. Overall, the APE was 6.0 +/
      4.5% and the rate of substantial error was 17.4% (n = 174). There was no
      significant difference in APE or rate of substantial error between BMI groups. In
      the final multivariable logistic regression model, the rate of substantial error
      was increased in women with oligohydramnios (OR 1.79; 95% CI: 1.10-2.92).
      Furthermore, oligohydramnios was significantly more likely to overestimate EFW
      while polyhydramnios was more likely to underestimate EFW. Maternal BMI did not
      affect the accuracy of sonographic EFW. CONCLUSION:  Sonographic EFW may be
      affected by extremes of AFI in the postdates period. Maternal BMI does not affect
      EFW accuracy at 40 to 42 weeks.

PMID- 29320803
TI  - Moving pulmonary rehabilitation forward in COPD: Stepping towards (home-based)
      action.

PMID- 29320804
TI  - Misidentification of genome assemblies in public databases: The case of
      Naumovozyma dairenensis and proposal of a protocol to correct misidentifications.
AB  - Online sequence databases such as NCBI GenBank serve as a tremendously useful
      platform for researchers to share and reuse published data. However, submission
      systems lack control for errors such as organism misidentification, which once
      entered in the database can be propagated and mislead downstream analyses. Here
      we present an illustrating case of misidentification of Candida albicans from a
      clinical sample as Naumovozyma dairenensis based on whole-genome shotgun data.
      Analyses of phylogenetic markers, read mapping and single nucleotide
      polymorphisms served to correct the identification. We propose that the routine
      use of such analyses could help to detect misidentifications arising from
      unsupervised analyses and correct them before they enter the databases. Finally,
      we discuss broader implications of such misidentifications and the difficulty of
      correcting them once they are in the records.

PMID- 29320805
TI  - Success rate of medical thoracoscopy and talc pleurodesis in malignant pleurisy:
      A single-centre experience.
AB  - BACKGROUND AND OBJECTIVE: Malignant pleurisy is associated with advanced
      oncological disease and dyspnoea is the most common presenting symptom.
      Pleurodesis is the preferred palliative and supportive treatment option,
      targeting symptom relief. The identification of clinical and endoscopic features
      that determine the success of talc pleurodesis in malignant pleurisy could guide
      clinical decision-making. METHODS: All symptomatic patients with malignant
      pleurisy subjected to talc pleurodesis through medical thoracoscopy between
      January 2012 and December 2015 were included. Univariate and multivariate
      analyses were performed to identify factors associated with successful
      pleurodesis. RESULTS: Of the 155 patients, 122 (78%) were classified as having a
      successful pleurodesis based on clinical and radiological criteria. Factors
      associated with unsuccessful pleurodesis (univariate analysis) were the presence
      of pleural adhesions (odds ratio (OR): 0.43 (95% CI: 0.19-0.96); P = 0.04),
      extensive spread of pleural lesions (OR: 0.17 (95% CI: 0.05-0.59); P = 0.001),
      the use of systemic corticosteroids (OR: 0.28 (95% CI: 0.10-0.83); P = 0.02) and
      a prolonged time period between the clinical diagnosis of the pleural effusion
      and the moment of pleurodesis (OR: 0.14 (95% CI: 0.06-0.32); P < 0.0001). The
      latter being associated with failure of pleurodesis in a multivariate analysis
      (OR: 0.08 (95% CI: 0.01-0.25); P < 0.0001). Chest ultrasound prior to pleurodesis
      showed a sensitivity of 91% and a specificity of 88% in predicting the success of
      pleurodesis. CONCLUSION: The success rate of pleurodesis in malignant pleurisy
      could potentially be enhanced by correct patient selection and early referral for
      pleurodesis. Ultrasonic assessment of pleural adhesions and potential lung
      expansion prior to pleurodesis is useful in clinical decision-making.

PMID- 29320806
TI  - Experiences of living kidney donors during the donation process.
AB  - BACKGROUND: The shortage of organs from deceased donors has led to more living
      donation. Furthermore, immunological developments have made it possible to
      perform kidney transplantation despite preformed antibodies against the donor
      organ. This has led to a broader recruitment base of living donors. OBJECTIVE:
      The objective was to investigate experiences and considerations on becoming, and
      during the process of being, a living kidney donor. MATERIALS AND METHODS:
      Interviews and participant observation were conducted before, during and after
      the donation. Data were analysed in accordance with Ricoeur's theory of
      interpretation on three levels: naive reading, structural analysis and critical
      interpretation and discussion. Eighteen potential donors over the age of 18 were
      included. RESULTS: Potential donors' decision to donate was based on a desire to
      help the recipient. At all stages of the process, donors experienced joy,
      dilemmas, vulnerability and hope. Rejected donors experienced frustration and
      disappointment. The accepted donors experienced both joy and vulnerability.
      Interaction between the donor and the recipient and the relatives played a
      significant role. The transition from being a healthy individual to being a
      surgical patient was an overwhelming experience. CONCLUSION: The process of
      donating a kidney and the return to everyday life involved significant
      experiences of joy, dilemmas, vulnerability and hope that influenced donors'
      lives on physical, psychological and social levels. Support and clear
      communication from the health professionals was essential.

PMID- 29320807
TI  - Overlap of interstitial pneumonia with autoimmune features with undifferentiated
      connective tissue disease and contribution of UIP to mortality.
AB  - BACKGROUND AND OBJECTIVE: Criteria for interstitial pneumonia with autoimmune
      features (IPAF) were recently established for research purposes in a joint
      statement from the European Respiratory Society (ERS) and American Thoracic
      Society (ATS). We reviewed the utility of these criteria in patients previously
      diagnosed as broadly defined undifferentiated connective tissue disease (UCTD)
      and noted overlapping IPAF findings. Additional review was given to IPAF patients
      with usual interstitial pneumonia (UIP) on histopathology or radiology in terms
      of survival and outcome. METHODS: Patients with prior UCTD-interstitial lung
      disease (ILD) were screened by ERS/ATS criteria for IPAF. Clinical data along
      with all-cause mortality were collated and compared with selected idiopathic
      pulmonary fibrosis (IPF) patients from the same study period. Survival was
      compared between IPAF subgroups with and without UIP features. RESULTS: One
      hundred and one UCTD-ILD subjects (91%) evaluated from 2005 to 2012 also met
      strict criteria for IPAF. Frequent clinical findings included Raynaud's
      phenomenon, positive anti-nuclear antibody (ANA) and non-specific interstitial
      pneumonia (NSIP) pattern on chest computed tomography (CT). Nineteen had features
      of UIP either on histopathology or CT imaging. As compared with IPF, IPAF
      patients had overall better survival except in those with UIP features.
      CONCLUSION: Current IPAF criteria encompassed the majority of broadly defined
      UCTD-ILD and included those with UIP findings. Survival compared with IPF in
      those with UIP was similar. Further studies are necessary to refine IPAF
      definitions for clinical use and guide directed management strategies.

PMID- 29320808
TI  - Paid Family Leave, Fathers' Leave-Taking, and Leave-Sharing in Dual-Earner
      Households.
AB  - Using difference-in-difference and difference-in-difference-in-difference
      designs, we study California's Paid Family Leave (CA-PFL) program, the first
      source of government-provided paid parental leave available to fathers in the
      Unites States. Relative to the pre-treatment mean, fathers of infants in
      California are 46 percent more likely to be on leave when CA-PFL is available. In
      households where both parents work, we find suggestive evidence that CA-PFL
      increases both father-only leave-taking (i.e., father on leave while mother is at
      work) and joint leave-taking (i.e., both parents on leave at the same time).
      Effects are larger for fathers of first-born children than for fathers of later
      born children.

PMID- 29320809
TI  - Does Paid Family Leave Reduce Nursing Home Use? The California Experience.
AB  - The intent of Paid Family Leave (PFL) is to make it financially easier for
      individuals to take time off from paid work to care for children and seriously
      ill family members. Given the linkages between care provided by family members
      and the usage of paid services, we examine whether California's PFL program
      influenced nursing home utilization in California during the 1999 to 2008 period.
      This is the first empirical study to examine the effects of PFL on long-term care
      patterns. Multivariate difference-indifference estimates across alternative
      comparison groups provide consistent evidence that the implementation of PFL
      reduced the proportion of the elderly population in nursing homes by 0.5 to 0.7
      percentage points. Our preferred estimate, employing an empirically-matched group
      of control states, finds that PFL reduced nursing home usage by about 0.65
      percentage points. For California, this represents an 11 percentrelative decline
      in elderly nursing home utilization.

PMID- 29320810
TI  - Breaking Habits: The Effect of the French Vending Machine Ban on School Snacking
      and Sugar Intakes.
AB  - This paper estimates the effect of the 2005 vending machine ban in French
      secondary schools on nutrient intakes and on the frequency of morning snacking at
      school. Using data before and after the ban, and exploiting the discontinuity
      associated with the age-dependent exposure to the ban, we specify a difference-in
      differences regression discontinuity design. Since the relationship between age
      at-interview and school level is not precise, we introduce fuzziness in the
      model. We find that the ban has generated a 10-gram reduction in sugar intakes
      from morning snacks at school, and a significant reduction in the frequency of
      these morning snacks. However, we find no evidence that the intervention affects
      total daily intakes, and our results are suggestive of compensation effects.

PMID- 29320811
TI  - Vaccination Policies: Requirements and Exemptions for Entering School.
AB  - (1) According to the World Health Organization, immunization prevents between 2
      million to 3 million deaths every year across the world. (2) When immunization
      rates are high, herd immunity develops and limits the spread of the disease,
      which helps protect those who cannot be vaccinated. (3) Vaccination rates for
      measles, mumps and rubella vary across the United States, ranging from 85.6
      percent in Washington, D.C., to 99.4 percent in Mississippi.

PMID- 29320812
TI  - Celebrating Ten Years of ACS Applied Materials & Interfaces.

PMID- 29320814
TI  - Genotypic Identification of Cystoisospora in Immunocompromised Patients Using Tm
      Variation Analysis.
AB  - Cystoisospora is responsible for morbidity in immunocompromised patients. PCR is
      sensitive for diagnosing Cystoisospora; however, it needs reevaluation for
      differential molecular diagnosis of cystoisosporiasis. We aimed at evaluating
      melting curve analysis (MCA) after real-time PCR (qPCR) in diagnosis and
      genotyping of Cystoisospora as an alternative to conventional PCR. We included
      293 diarrheic stool samples of patients attending the Department of Clinical
      Oncology and Nuclear Medicine of Cairo University Hospitals, Egypt. Samples were
      subjected to microscopy, nested PCR (nPCR), and qPCR targeting the internal
      transcribed spacer 2 region (ITS2) of the ribosomal RNA (r RNA) gene followed by
      melting temperatures (Tms) analysis and comparing the results to PCR-RFLP banding
      patterns. Using microscopy and ITS2-nPCR, 3.1% and 5.8% of cases were
      Cystoisospora positive, respectively, while 10.9% were positive using qPCR.
      Genotyping of Cystoisospora by qPCR-MCA revealed 2 genotypes. These genotypes
      matched with 2 distinct melting peaks with specified Tms at 85.8 degrees C and
      88.6 degrees C, which indicated genetic variation among Cystoisospora isolates in
      Egypt. Genotype II proved to be more prevalent (65.6%). HIV-related Kaposi
      sarcoma and leukemic patients harbored both genotypes with a tendency to genotype
      II. Genotype I was more prevalent in lymphomas and mammary gland tumors while
      colorectal and hepatocellular tumors harbored genotype II suggesting that this
      genotype might be responsible for the development of cystoisosporiasis in
      immunocompromised patients. Direct reliable identification and differentiation of
      Cystoisospora species could be established using qPCR-Tms analysis which is
      useful for rapid detection and screening of Cystoisospora genotypes principally
      in high risk groups.

PMID- 29320813
TI  - Therapeutic Effects of Resiniferatoxin Related with Immunological Responses for
      Intestinal Inflammation in Trichinellosis.
AB  - The immune response against Trichinella spiralis at the intestinal level depends
      on the CD4+ T cells, which can both suppress or promote the inflammatory response
      through the synthesis of diverse cytokines. During the intestinal phase, the
      immune response is mixed (Th1/Th2) with the initial predominance of the Th1
      response and the subsequent domination of Th2 response, which favor the
      development of intestinal pathology. In this context, the glucocorticoids (GC)
      are the pharmacotherapy for the intestinal inflammatory response in
      trichinellosis. However, its therapeutic use is limited, since studies have shown
      that treatment with GC suppresses the host immune system, favoring T. spiralis
      infection. In the search for novel pharmacological strategies that inhibit the
      Th1 immune response (proinflammatory) and assist the host against T. spiralis
      infection, recent studies showed that resiniferatoxin (RTX) had anti-inflammatory
      activity, which decreased the serum levels of IL-12, INF-gamma, IL-1beta, TNF
      alpha, NO, and PGE2, as well the number of eosinophils in the blood, associated
      with decreased intestinal pathology and muscle parasite burden. These researches
      demonstrate that RTX is capable to inhibit the production of Th1 cytokines,
      contributing to the defense against T. spiralis infection, which places it as a
      new potential drug modulator of the immune response.

PMID- 29320815
TI  - Comparison of Placenta PCR and Maternal Serology of Aborted Women for Detection
      of Toxoplasma gondii in Ardabil, Iran.
AB  - Primary maternal infection with toxoplasmosis during pregnancy is frequently
      associated with transplacental transmission of the parasite to the fetus. This
      study was conducted to test the utility of PCR assay to detect recent infections
      with Toxoplasma in aborted women at various gestational ages who referred to
      Obstetrics and Gynecology Department of Alavi Hospital in Ardabil during 2014 and
      2016. Two hundred women with a history of single or repeated abortion were
      investigated in this study. Blood samples were tested for specific anti
      Toxoplasma IgM and IgG antibodies by ELISA. According to the results, 53.5% of
      the women under study were positive for anti-Toxoplasma antibodies: 4.0% of them
      had IgM, 43.0% had IgG, and 6.5% had both IgM and IgG. Subsequently, Nested-PCR
      analysis was used to detect T. gondii DNA in the placenta of subjects. In 10.5%
      of the women, the results were positive for 529 bp element of T. gondii. Among
      them, 5 (23.8%) cases were IgM positive, 1 (4.8%) case was IgG positive, and 11
      (52.4%) were both IgM and IgG positive. In 4 (19.0%) patients, none of the
      antibodies were found to be positive. In total, 16 patients had positive results
      in both ELISA and PCR methods, and 174 cases had negative results for new
      infection. The findings of this study revealed that T. gondii might be one of the
      significant factors leading to abortion, and that the analysis of placenta can be
      important in order to achieve increased detection sensitivity.

PMID- 29320817
TI  - Development of Monoclonal Antibodies for Diagnosis of Plasmodium vivax.
AB  - Plasmodium lactate dehydrogenase (pLDH) is a strong target antigen for the
      determination of infection with Plasmodium species specifically. However, a more
      effective antibody is needed because of the low sensitivity of the current
      antibody in many immunological diagnostic assays. In this study, recombinant
      Plasmodium vivax LDH (PvLDH) was experimentally constructed and expressed as a
      native antigen to develop an effective P. vivax-specific monoclonal antibody
      (mAb). Two mAbs (2CF5 and 1G10) were tested using ELISA and immunofluorescence
      assays (IFA), as both demonstrated reactivity against pLDH antigen. Of the 2
      antibodies, 2CF5 was not able to detect P. falciparum, suggesting that it might
      possess P. vivax-specificity. The detection limit for a pair of 2 mAbs-linked
      sandwich ELISA was 31.3 ng/ml of the recombinant antigen. The P. vivax-specific
      performance of mAbs-linked ELISA was confirmed by in vitro-cultured P. falciparum
      and P. vivax-infected patient blood samples. In conclusion, the 2 new antibodies
      possessed the potential to detect P. vivax and will be useful in immunoassay.

PMID- 29320816
TI  - IL-12 and IL-23 Production in Toxoplasma gondii- or LPS-Treated Jurkat T Cells
      via PI3K and MAPK Signaling Pathways.
AB  - IL-12 and IL-23 are closely related in structure, and have been shown to play
      crucial roles in regulation of immune responses. However, little is known about
      the regulation of these cytokines in T cells. Here, we investigated the roles of
      PI3K and MAPK pathways in IL-12 and IL-23 production in human Jurkat T cells in
      response to Toxoplasma gondii and LPS. IL-12 and IL-23 production was
      significantly increased in T cells after stimulation with T. gondii or LPS. T.
      gondii and LPS increased the phosphorylation of AKT, ERK1/2, p38 MAPK, and JNK1/2
      in T cells from 10 min post-stimulation, and peaked at 30-60 min. Inhibition of
      the PI3K pathway reduced IL-12 and IL-23 production in T. gondii-infected cells,
      but increased in LPS-stimulated cells. IL-12 and IL-23 production was
      significantly reduced by ERK1/2 and p38 MAPK inhibitors in T. gondii- and LPS
      stimulated cells, but not in cells treated with a JNK1/2 inhibitor. Collectively,
      IL-12 and IL-23 production was positively regulated by PI3K and JNK1/2 in T.
      gondii-infected Jurkat cells, but negatively regulated in LPS-stimulated cells.
      And ERK1/2 and p38 MAPK positively regulated IL-12 and IL-23 production in Jurkat
      T cells. These data indicate that T. gondii and LPS induced IL-12 and IL-23
      production in Jurkat T cells through the regulation of the PI3K and MAPK
      pathways; however, the mechanism underlying the stimulation of IL-12 and IL-23
      production by T. gondii in Jurkat T cells is different from that of LPS.

PMID- 29320818
TI  - Zoonotic Trematode Metacercariae in Fish from Yangon, Myanmar and Their Adults
      Recovered from Experimental Animals.
AB  - A survey was performed to investigate the infection status of zoonotic trematode
      (ZT) metacercariae in fish from a local market in Yangon City, Myanmar. A total
      of 264 fish (12 species) were collected through 4 times from December 2013 to
      June 2015. All collected fish were transferred to our laboratory on ice and
      examined by the artificial digestion method. More than 7 species of ZT
      metacercariae, i.e., Haplorchis taichui, H. pumilio, H. yokogawai, Centrocestus
      spp., Stellantchasmus falcatus, Pygidiopsis cambodiensis, and Procerovum sp. were
      detected. Metacercariae of H. taichui were collected in 58 (42.3%) out of 137
      fish (5 species), and their average density was 42.9 per fish infected.
      Metacercariae of H. pumilio were detected in 96 (49.0%) out of 196 fish (9
      species), and their average density was 23.6 per fish infected. H. yokogawai
      metacercariae were found in 40 (50.0%) out of 80 fish (5 species), and
      Centrocestus spp. metacercariae in 91 (50.8%) out of 179 fish (8 species), and
      their densities were 306 and 25.8 per fish infected, respectively. Metacercariae
      of S. falcatus and P. cambodiensis were detected only in mullets, Chelon
      macrolepis. A total of 280 Procerovum sp. metacercariae were found in 6 out of 12
      climbing perch, Anabas testudineus. Morphological characteristics of adult flukes
      recovered from experimental animals were described. It has been first confirmed
      that fish from Yangon, Myanmar are commonly infected with various species of ZT
      metacercariae.

PMID- 29320819
TI  - Molecular and Biochemical Characterization of Opisthorchis viverrini
      Calreticulin.
AB  - Calreticulin (CALR), a multifunctional protein thoroughly researched in mammals,
      comprises N-, P-, and C-domain and has roles in calcium homeostasis, chaperoning,
      clearance of apoptotic cells, cell adhesion, and also angiogenesis. In this
      study, the spatial and temporal expression patterns of the Opisthorchis viverrini
      CALR gene were analyzed, and calcium-binding and chaperoning properties of
      recombinant O. viverrini CALR (OvCALR) investigated. OvCALR mRNA was detected
      from the newly excysted juvenile to the mature parasite by RT-PCR while specific
      antibodies showed a wide distribution of the protein. OvCALR was localized in
      tegumental cell bodies, testes, ovary, eggs, Mehlis' gland, prostate gland, and
      vitelline cells of the mature parasite. Recombinant OvCALR showed an in vitro
      suppressive effect on the thermal aggregation of citrate synthase. The
      recombinant OvCALR C-domain showed a mobility shift in native gel electrophoresis
      in the presence of calcium. The results imply that OvCALR has comparable function
      to the mammalian homolog as a calcium-binding molecular chaperone. Inferred from
      the observed strong immunostaining of the reproductive tissues, OvCALR should be
      important for reproduction and might be an interesting target to disrupt parasite
      fecundity. Transacetylase activity of OvCALR as reported for calreticulin of
      Haemonchus contortus could not be observed.

PMID- 29320820
TI  - First Molecular Characterization of Hypoderma actaeon in Cattle and Red Deer
      (Cervus elaphus) in Portugal.
AB  - Hypoderma spp. larvae cause subcutaneous myiasis in several animal species. The
      objective of the present investigation was to identify and characterize
      morphologically and molecularly the larvae of Hypoderma spp. collected from
      cattle (Bos taurus taurus) and red deer (Cervus elaphus) in the district of
      Castelo Branco, Portugal. For this purpose, a total of 8 larvae were collected
      from cattle (n=2) and red deer (n=6). After morphological identification of
      Hypoderma spp. larvae, molecular characterization was based on PCR-RFLP and
      mitochondrial CO1 gene sequence analysis. All larvae were morphologically
      characterized as the third instar larvae (L3) of H. actaeon. Two restriction
      enzymes were used for molecular identification of the larvae. TaqI restriction
      enzyme was not able to cut H. actaeon. However, MboII restriction enzyme
      differentiated Hypoderma species showing 210 and 450 bp bands in H. actaeon.
      Furthermore, according to the alignment of the mt-CO1 gene sequences of Hypoderma
      species and to PCR-RFLP findings, all the identified Hypoderma larvae were
      confirmed as H. actaeon. This is the first report of identification of Hypoderma
      spp. (Diptera; Oestridae) from cattle and red deer in Portugal, based on
      morphological and molecular analyses.

PMID- 29320821
TI  - A Case of Biliary Ascariasis in Korea.
AB  - Biliary ascariasis is still the leading cause of surgical complication of
      ascariasis, though its incidence has been dramatically reduced. Herein, we report
      a case of biliary ascariasis for the purpose of enhancing awareness of parasitic
      infections as a possible cause. A 72-year-old male visited the emergency room of
      Dankook University Hospital on 12 July 2015, complaining of right-upper-quadrant
      pain. By endoscopic retrograde cholangiopancreatography (ERCP), a tubular filling
      defect in the right hepatic duct was detected. The defect was endoscopically
      removed and diagnosed as an adult female of Ascaris lumbricoides worm, of 30 cm
      length. Upon removal of the worm, the pain subsided, and the patient was
      discharged without any complication. When treating cases of biliary colic,
      physicians should not neglect biliary ascariasis as the possible cause.

PMID- 29320822
TI  - Antimalarial Activity of C-10 Substituted Triazolyl Artemisinin.
AB  - We synthesized C-10 substituted triazolyl artemisinins by the Huisgen
      cycloaddition reaction between dihydroartemisinins (2) and variously substituted
      1, 2, 3-triazoles (8a-8h). The antimalarial activities of 32 novel artemisinin
      derivatives were screened against a chloroquine-resistant parasite. Among them,
      triazolyl artemisinins with electron-withdrawing groups showed stronger
      antimalarial activities than those shown by the derivatives having electron
      donating groups. In particularly, m-chlorotriazolyl artemisinin (9d-12d) showed
      antimalarial activity equivalent to that of artemisinin and could be a strong
      drug candidate.

PMID- 29320823
TI  - First Blindness Cases of Horses Infected with Setaria Digitata (Nematoda:
      Filarioidea) in the Republic of Korea.
AB  - Ocular setariases of cattle were reported but those of equine hosts have never
      been reported in the Republic of Korea (Korea). We found motile worms in the
      aqueous humor of 15 horses (Equus spp.) from 12 localities in southern parts of
      Korea between January 2004 and November 2017. After the affected animals were
      properly restrained under sedation and local anesthesia, 10 ml disposable syringe
      with a 16-gauge needle was inserted into the anterior chamber of the affected eye
      to successfully remove the parasites. The male worm that was found in 7 of the
      cases showed a pair of lateral appendages near the posterior terminal end of the
      body. The papillar arrangement was 3 pairs of precloacal, a pair of adcloacal,
      and 3 pairs of postcloacal papillae, plus a central papilla just in front of the
      cloaca. The female worms found in the eyes of 8 horses were characterized by the
      tapering posterior terminal end of the body with a smooth knob. Worms were all
      identified as Setaria digitata (von Linstow, 1906) by the morphologic
      characteristics using light and electron microscopic observations. This is the
      first blindness cases of 15 horses infected with S. digitata (Nematoda:
      Filarioidea) in Korea.

PMID- 29320824
TI  - Seroprevalence of Dirofilaria immitis in Cats from Liaoning Province,
      Northeastern China.
AB  - The present study was performed to investigate the seroprevalence and risk
      factors for Dirofilaria immitis infection in cats from Liaoning province,
      northeastern China. From October 2014 to September 2016, sera of 651 cats,
      including 364 domestic cats and 287 feral cats (332 females and 319 males) were
      assessed. They were tested for the presence of D. immitis antigen using SNAP
      Heartworm RT test kit. In this population, the average prevalence was 4.5%. Age
      and rearing conditions (feral or domestic) were found to be associated with the
      prevalence of D. immitis. The prevalence was significantly higher in feral cats
      compared with domestic cats (8.4% vs 1.4%, P<0.01). There was no significant
      difference between males and females (4.7% vs 4.2%, P>0.05), but older cats (>=3
      years old) showed a statistically higher prevalence compared with younger cats
      (<3 years old) in feral populations (16.8 vs 2.4%, P<0.01), while the difference
      between the age groups was not statistically significant in domestic cats (2.4%
      vs 0.51%, P>0.05), all these results suggest that outdoor exposure time may be
      one of the most important factors for D. immitis prevalence in cats. Results
      reveal that D. immitis are prevalence in domestic and feral cats in northeastern
      China, which indicates that appropriate preventive measures should be taken to
      decrease the incidence of feline heartworm disease in Liaoning province,
      northeastern China.

PMID- 29320826
TI  - [Wisdom of the Chinese experts from the "Chinese consensus report on diagnosis
      and management of severe asthma"].

PMID- 29320827
TI  - [Personalized treatment of severe asthma].

PMID- 29320825
TI  - Practical Algorisms for PCR-RFLP-Based Genotyping of Echinococcus granulosus
      Sensu Lato.
AB  - Echinococcus granulosus sensu lato (s.l.) is a causative agent of cystic
      echinococcosis or cystic hydatid disease in humans and domestic and wild animals.
      The disease is a serious health problem in countries associated with poverty and
      poor hygiene practices, particularly in livestock raising. We introduced a
      practical algorism for genotyping the parasite, which may be useful to many
      developing countries. To evaluate the efficiency of the algorism, we genotyped 3
      unknown strains isolated from human patients. We found that unknowns 1 and 3 were
      included in G1, G2, and G3 genotypes group and unknown 2 was included in G4
      genotype (Echinococcus equinus) according to the algorisms. We confirmed these
      results by sequencing the 3 unknown isolates cox1 and nad1 PCR products. In
      conclusion, these new algorisms are very fast genotype identification tools that
      are suitable for evaluating E. granulosus s.l. isolated from livestock or
      livestock holders, particularly in developing countries.

PMID- 29320829
TI  - [Novel insights into the mechanism of airway inflammation in severe asthma].

PMID- 29320828
TI  - [The epidemiology and burden of severe asthma].

PMID- 29320830
TI  - [A multi-center retrospective study of clinical characteristics and
      hospitalization costs of patients hospitalized for asthma exacerbation in China
      during 2013-2014].
AB  - Objective: To study the characteristics of patients hospitalized for asthma
      exacerbation in 29 teaching hospitals in China and to evaluate the
      hospitalization costs of these patients. Methods: This was a retrospective study
      and involved patients hospitalized for asthma exacerbation in 29 hospitals
      throughout China during 2013-2014. Information about the demographic features,
      conditions before the admission, the outcome, the complications, and the costs
      was collected using the pre-designed case report form. The influencing factors of
      the hospitalization costs were analyzed. Results: 3 240 asthmatic patients (1 369
      males and 1 871 females) were included and data were analyzed. There were 41.5%
      (1 346/3 240) patients who had a history of previous hospitalization or emergency
      department visits during the last year. Only 28.0% (907/3 240) patients had used
      asthma-controlling medications regularly before the admission. Seventy
      three(2.3%) patients were admitted to ICU and used mechanical ventilation.
      Mortality among these patients hospitalized for asthma exacerbation was 0.25%
      (8/3 240). The median hospitalization costs was 9 045(6 431, 13 035) RMB. The
      costs of medications, examinations and treatment accounted for 52.1%, 27.6%, and
      9.6% respectively. The costs of asthma medications accounted for only 22.7% of
      the total medication costs, while the costs of antibiotics accounted for 44.0%.
      The patients who were admitted to ICU, used mechanical ventilation, complicated
      with pneumonia, or had a history of hospitalization or emergency department
      visits during the last year due to asthma exacerbations tended to cost more.
      Conclusion: In this study, we demonstrated that only a minority of the patients
      had used asthma controllers regularly before the admissions with exacerbations.
      The in-hospital mortality of asthma patients in this study was much lower than
      that reported in other countries. The average cost of hospitalization was much
      higher than the yearly cost of maintenance therapy. Medication was the
      predominant component of the total hospitalization costs, and the costs of
      antibiotics made up the major part of the total medication costs.

PMID- 29320831
TI  - [Efficacy and safety of anti-interleukin-5 therapy in patients with asthma:
      systematic reviews].
AB  - Objective: To evaluate the efficacy and safety of anti-Interleukin-5 therapy in
      patients with asthma. Methods: Data were collected from PubMed, E-Mbase,
      Springer, Ovid, Cochrane Library, ClinicalTrials.gov, CNKI and Wanfang database (
      Feb 2017). Bibliographies of the retrieved articles were checked and analyzed.
      Results: Twenty publications involving a total of 6 406 patients were used in the
      analysis, including 23 randomly controlled trials (RCTs) which compared anti
      interleukin 5 monoclonal antibody with placebo. Pooled analyses showed that anti
      interleukin 5 monoclonal antibody significantly reduced exacerbation risk
      [RR=0.66, 95%CI(0.59, 0.73)], increased FEV(1)[MD=0.10, 95%CI(0.07, 0.13)] and
      FEV(1)% predicted [MD=3.90, 95%CI(1.86, 5.95)], and improved the scores on the
      Asthma Quality of Life Questionnaire (AQLQ) [MD=0.24, 95%CI(0.16, 0.32)]. Anti
      interleukin 5 monoclonal antibody was also associated with significantly
      decreased risk of adverse events than placebo[OR=0.71, 95%CI(0.58, 0.87)].
      Conclusion: Anti-interleukin 5 monoclonal antibody reduces the risk of
      exacerbations and improves quality of life in patients with asthma, and is
      tolerated well.

PMID- 29320832
TI  - [Diagnostic value of endobronchial ultrasonography with a guide sheath for
      peripheral pulmonary ground glass opacity].
AB  - Objective: To explore the diagnostic value of endobronchial ultrasonography with
      a guide sheath (EBUS-GS) for peripheral pulmonary ground glass opacity (GGO).
      Methods: The clinical data of 27 consecutive patients with 27 GGOs diagnosed by
      EBUS-GS between November 2014 to December 2015 in our Cancer Hospital were
      retrospectively analyzed. The average age of these 27 patients, including 9 males
      and 18 females, was 59+/-11 years. The median lesion size of the 27 GGOs was
      2.9+/-1.2 cm, including 24 mixed GGOs and 3 pure GGOs. EBUS images of all 27 GGOs
      were evaluated, cytological, histological and combination diagnosis analyzed, and
      complications observed. Results: Under thin bronchoscope, 2 out of 27 cases
      showed bronchial stenosis, 1 showed bronchial stenosis with mucosal swelling, and
      the other 24 did not show abnormalities. Twenty-five out of 27 GGOs were found by
      EBUS, including 22 cases of mGGO and 3 of pGGO. In these ultrasonic images of 22
      mGGOs, 18 showed mixed blizzard sign, 3 showed diffusely heterogeneous acoustic
      shadow and 1showed blizzard sign. Ultrasonic images of 3 pGGOs all appeared as
      blizzard sign. Twenty-six cytological specimens were obtained, and 16 were
      diagnosed clearly. All 27 histological specimens were collected, and 18 were
      diagnosed clearly. Nineteen of 27 cases were diagnosed by combination of
      cytological and histological specimens. One complication of EBUS-GS with mild
      bleeding was observed, and hemorrhage was terminated by conservative treatment.
      Conclusions: EBUS-GS is valuable for GGO diagnosis with less complications and
      higher safety. GGO ultrasonic image manifested as mixed blizzard sign, blizzard
      sign or diffusely heterogeneous acoustic shadow.

PMID- 29320833
TI  - [Analysis of 9 cases of nodular type of pulmonary cryptococcosis with coexisting
      lung cancer confirmed by pathological examinations].
AB  - Objective: To describe the characteristics of the nodular type of pulmonary
      cryptococcosis (PC) with coexisting lung cancer. Methods: A total of 9 cases of
      PC with coexisting lung cancer, admitted to Fuzhou Pulmonary Hospital of Fujian
      from 1st January 2009 to 31th December 2016, and confirmed by pathological
      examinations, were studied and the related literature were reviewed. Results: The
      patients consisted of 1 male and 8 females, with a mean age of (53+/-10) years
      (range, 38 to 68 years). Four patients (44.4%) had underlying diseases, 3 with
      diabetes mellitus and 1 with gastric cancer surgery. The main clinical
      manifestations of most cases were cough and phlegm. The lesions of PC on chest CT
      were mostly solitary or multiple nodules with a diameter < 1 cm, and the lesions
      of carcinoma were shown as solitary nodules with a variety of signs suggestive of
      malignancy. All the patients were confirmed to have concomitant PC and lung
      adenocarcinoma by pathological examinations. Lung cancer stage was early (Tis and
      I-II) in 88.9 % (8 cases) of the cases. All the patients received surgery and
      postoperative medical therapy. The prognosis was relatively good in most of them
      except 1 case with death due to lung cancer metastasis and 1 case with lung
      cancer recurrence. Conclusions: Coexistence of PC and lung cancer is rare and the
      clinical symptoms are not specific. When PC coexists with carcinoma and manifests
      as pulmonary nodule, it mimics malignant lesions and is extremely easy to be
      misdiagnosed. Therefore PC must be considered in the differential diagnosis of
      pulmonary nodules.

PMID- 29320834
TI  - [The role and mechanism of mesenchymal stem cell in modulating human pulmonary
      microvascule endothelial cell permeability via paracrine hepatocyte growth
      factor].
AB  - Objective: To explore the role and mechanism of mesenchymal stem cell (MSC) in
      modulating human pulmonary microvascular endothelial cell (HPMECs) permeability
      via hepatocyte growth factor (HGF). Methods: The study introduced a co-cultured
      model between HPMECs and human mesenchymal stem cell conditioned media (MSC-CM)
      collected from MSCs after 24 h hypoxia culture, and meanwhile HGF was neutralized
      in MSC-CM by anti-HGF antibody respectively, followed by lipopolysaccharide (LPS)
      stimulation. Finally, the following measurements were performed: the permeability
      of HPMECs, the protein expression of vascular endothelial cadherin (VE-cadherin),
      Occludin in HPMECs by Western blot, HPMECs apoptosis by Annexin V-FITC/PI and
      HPMECs proliferation by 3-(4, 5)-dimethylthiahiazo (-z-y1)-3, 5-di-
      phenytetrazoliumromide(MTT). Results: Compared to LPS group (4.15+/-0.88), MSC-CM
      reduced endothelial paracellular permeability injured by LPS(1.56+/-0.36,
      P<0.01), however, the MSC-CM effect was significantly blocked by anti-HGF
      antibody(3.11+/-0.74, P<0.05). Furthermore MSC-CM significantly increased the
      expression of VE-cadherin(0.71+/-0.05 vs. 0.38+/-0.19, P<0.05)and Occludin
      protein(0.96+/-0.05 vs. 0.51+/-0.02, P<0.05) in HPMECs, which was significantly
      blocked by anti-HGF antibody (P<0.05). MSC-CM significantly reduced the number of
      early apoptotic cells (6.82+/-1.80 vs. 17.09+/-1.89, P<0.05). However, the effect
      of MSC-CM was significantly blocked by neutralizing HGF (12.07+/-0.98, P<0.01).
      The cell viability results by MTT assay confirmed that MSC-CM(6.82+/-1.80,
      P<0.05)restored cell viability to a greater extent than LPS stimulation
      only(0.47+/-0.09), and meanwhile the MSC-CM effect was significantly inhibited by
      neutralizing HGF from MSC-CM with anti-HGF antibody (0.69+/-0.29, P<0.05).
      Conclusion: HGF secreted by MSCs reduces endothelial cell paracelluar
      permeability induced by LPS, and the possible mechanisms include remodelling of
      endothelial intercellular adherence junction, promoting endothelial cell
      proliferation and restraining endothelial cell apoptosis.

PMID- 29320835
TI  - [Advances in signal pathway of macrophage polarization in tuberculosis].

PMID- 29320836
TI  - [The progress of tracheobronchopathia osteochondroplastica].

PMID- 29320837
TI  - [Role of cigarette smoke in the pathogenesis of pulmonary hypertension].

PMID- 29320838
TI  - [Advances in autoantibodies of idiopathic inflammatory myopathy and interstitial
      lung disease].

PMID- 29320839
TI  - Large vessel vasculitis: is it more common than usually assumed?
AB  - Not available.

PMID- 29320840
TI  - Microvascular damage evaluation in systemic sclerosis: the role of nailfold
      videocapillaroscopy and laser techniques.
AB  - Microvascular damage and a decrease in peripheral blood perfusion are typical
      features of systemic sclerosis (SSc) with serious clinical implications, not only
      for a very early diagnosis, but also for disease progression. Nailfold
      videocapillaroscopy is a validated and safe imaging technique able to detect
      peripheral capillary morphology, as well as to classify and to score any nailfold
      abnormalities into different microangiopathy patterns. Capillaroscopic analysis
      is now included in the ACR/EULAR classification criteria for SSc. The decrease in
      peripheral blood perfusion is usually associated with microvascular damage in
      SSc, which may be studied by different methods. Several of these make use of safe
      laser technologies. This paper focuses on these new clinical aspects to assess
      SSc microvascular impairment.

PMID- 29320841
TI  - The role of klotho in systemic sclerosis.
AB  - The aim was to evaluate the role of klotho in the pathogenesis of systemic
      sclerosis (SSc), through the measurement of its serum concentration in SSc
      patients compared to healthy controls, and to assess the association with
      cutaneous and visceral involvement. Blood samples obtained from both SSc patients
      and healthy controls were analysed by an ELISA assay for the detection of human
      klotho. SSc patients were globally evaluated for disease activity and assessed
      through the modified Rodnan's Skin Score, Medsger's scale, pulmonary function
      tests, 2D-echocardiography, nailfold capillaroscopy and laboratory tests. Our
      cohort consisted of 69 SSc patients (61 females, mean age 64.5+/-12.5 years,
      median disease duration 9.0 (IQR 8) years) and 77 healthy controls (28 females,
      mean age 49.7+/-10.2 years). In the group of SSc patients, 19 (27.5%) suffered
      from a diffuse form of SSc. All patients were receiving IV prostanoids, and some
      of them were concomitantly treated with immunosuppressive drugs (prednisone,
      hydroxychloroquine, mofetil mycophenolate, methotrexate, cyclosporin A and
      azathioprine). The median serum concentration of klotho was significantly lower
      in patients compared to controls (0.23 ng/mL vs 0.60 ng/mL; p<0.001). However,
      Spearman's test showed no significant association between klotho serum levels and
      disease activity, concerning either clinical, laboratory or instrumental
      findings. Our data show a significant deficit of klotho in SSc patients although
      any significant association was detected between klotho serum concentration and
      the clinical, laboratory or instrumental features of the disease. However, due to
      the limits of the study, further investigations are required.

PMID- 29320842
TI  - Carpal tunnel syndrome in HIV-positive patients coinfected with HCV.
AB  - A wide range of rheumatic and peripheral nervous system disorders may develop in
      patients with HIV infection, leading to pain, sensory symptoms, and muscle
      weakness. Over the past three decades, the progress in management of HIV disease
      with anti-retroviral therapy (ART) has resulted in increased life expectancy for
      people living with HIV disease. With this new chronicity of the disease has a
      constellation of chronic musculoskeletal, orthopaedic and rheumatic
      manifestations has emerged, as potential complications of the disease itself
      and/or the results of ART treatment regimen and/or because of expected age
      related symptoms/manifestations. The incidence of CTS in the general population
      is around 3.8% with clinical examination and, when electroneuromyography is used,
      it is 2.7%. In the HIV-positive population, the incidence is very close to that
      of the general population. The aim of this study was to evaluate the incidence of
      CTS and to identify factors influencing the development of CTS in HIV-infected
      patients attending our clinic. This syndrome has been associated with advanced
      HIV disease and the use of ART possibly due to an increased inflammatory state
      and the presence of concurrent HCV infection.

PMID- 29320843
TI  - Diagnostic utility of serum melatonin levels in systemic lupus erythematosus: a
      case-control study.
AB  - Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune inflammatory
      disease and early diagnosis is of clinical and therapeutic importance. Melatonin
      is an endogenous endolamine hormone that plays an important role in the immune
      system due to its anti-inflammatory action. This study was designed to assess
      serum melatonin levels in SLE patients and to evaluate the possible correlation
      between serum melatonin and patients' baseline characteristics. A case-control
      study was performed on 50 SLE patients (48 females and 2 males), diagnosed
      according to the revised 1997 ACR Criteria, and 25 healthy controls (24 females
      and 1 male), matched by age and sex. Daily serum melatonin levels were
      investigated in all participants using human melatonin enzyme linked
      immunosorbent assay (ELISA) kit (MYBIOSOURCE (MBS), United States). Serum
      melatonin concentration was significantly lower in patients with SLE compared to
      healthy controls (19.17+/-6.86 pg/mL vs 23.26+/-6.71 pg/mL, p=0.017). Serum
      melatonin concentration <=18.51 pg/mL was the optimum cut off value to
      differentiate between SLE patients and healthy controls with an accuracy of
      69.3%, a sensitivity of 66%, and a specificity of 76%. The positive predictive
      value (PPV) at pretest 50% was 73.3% and PPV at pretest 90% was 96.1%; the
      negative predictive value (NPV) at 10% was 95.3%. Patients' characteristics were
      not significantly correlated with serum melatonin concentrations using multiple
      logistic regression analysis. Serum melatonin was a valid measure to
      differentiate between SLE patients and healthy controls with good accuracy,
      sensitivity and specificity and PPV and NPV. There was no significant correlation
      between serum melatonin concentrations and patients' baseline characteristics.

PMID- 29320844
TI  - Demyelinating syndrome in SLE: review of different disease subtypes and report of
      a case series.
AB  - Demyelinating syndrome (DS) is a rare manifestation of systemic lupus
      erythematosus (SLE) (1%) with high clinical heterogeneity and potentially severe
      prognosis. It can represent a diagnostic and therapeutic challenge for
      clinicians. A recent study described 5 different patterns of demyelinating
      disease presentation, characterised by specific clinical, laboratory and brain
      and spine magnetic resonance imaging abnormalities: 1) neuromyelitis optica; 2)
      neuromyelitis optica spectrum disorders; 3) DS prevalently involving the brain;
      4) DS prevalently involving the brainstem; 5) clinically isolated syndrome. In
      this review we briefly discuss typical characteristics of each DS presentation in
      SLE and we describe 5 illustrative clinical cases, one for each subset of DS,
      considering both diagnostic and therapeutic options.

PMID- 29320845
TI  - Subcutaneous administration of tocilizumab is effective in myointimal hyperplasia
      remodelling in refractory Takayasu arteritis.
AB  - Takayasu arteritis (TA) is a chronic inflammatory disease of unknown origin that
      involves large and mediumsized arteries, primarily the aorta and its major
      branches. TA is a therapeutic challenge because corticosteroids and conventional
      immunosuppressive agents are not always effective or safe. Interleukin 6 (IL-6)
      has emerged as a key cytokine in the pathogenesis of TA and its serum levels have
      been shown to well correlate with disease activity. We report a 19 years old
      female patient with TA refractory to conventional immunosuppressive agents,
      successfully treated with subcutaneous tocilizumab, a humanized monoclonal
      antibody against IL-6 receptor, in which ultrasonography (US) was used as imaging
      tool to follow up the patient. Currently, clinical indices of disease activity,
      inflammatory markers, carotid intima media thickness (cIMT) as well as carotid
      pulse wave velocity (cPWV) normalised, while the prednisone dosage has been
      tapered. Tocilizumab appears to be a good option in refractory TA, with a
      remarkable steroid-sparing effect. In addition, it seems to have a favourable
      effect on endothelial function, as it improved cIMT and PWV.

PMID- 29320846
TI  - Plantar pain is not always fasciitis.
AB  - The case is described of a patient with chronic plantar pain, diagnosed as
      fasciitis, which was not improved by conventional treatment. Magnetic resonance
      imaging revealed flexor hallucis longus tenosynovitis, which improved after local
      glucocorticoid injection.

PMID- 29320847
TI  - New insights into the role of renal resident cells in the pathogenesis of lupus
      nephritis.
AB  - Systemic lupus erythematosus (SLE), an autoimmune disease of unknown etiology, is
      characterized by the production of autoantibodies and end-organ damage. Lupus
      nephritis affects up to 70% of patients with SLE and is the most critical
      predictor of morbidity and mortality. The immunopathogenesis of SLE is complex
      and most clinical trials of biologics targeting immune cells or their mediators
      have failed to show efficacy in SLE patients. It has therefore become
      increasingly clear that additional, local factors give rise to the inflammation
      and organ damage. In this review, we describe recent advances in the role of
      renal resident cells, including podocytes, mesangial cells, and epithelial cells,
      in the pathogenesis of lupus nephritis.

PMID- 29320848
TI  - Assessment of Metal Immission in Urban Environments Using Elemental
      Concentrations and Zinc Isotope Signatures in Leaves of Nerium oleander.
AB  - A thorough understanding of spatial and temporal emission and immission patterns
      of air pollutants in urban areas is challenged by the low number of air-quality
      monitoring stations available. Plants are promising low-cost biomonitoring tools.
      However, source identification of the trace metals incorporated in plant tissues
      (i.e., natural vs anthropogenic) and the identification of the best plant to use
      remain fundamental challenges. To this end, Nerium oleander L. collected in the
      city of Zaragoza (NE Spain) has been investigated as a biomonitoring tool for
      assessing the spatial immission patterns of airborne metals (Pb, Cu, Cr, Ni, Ce,
      and Zn). N. oleander leaves were sampled at 118 locations across the city,
      including the city center, industrial hotspots, ring-roads, and outskirts. Metal
      concentrations were generally higher within a 4 km radius around the city center.
      Calculated enrichment factors relative to upper continental crust suggest an
      anthropogenic origin for Cr, Cu, Ni, Pb, and Zn. Zinc isotopes showed significant
      variability that likely reflects different pollution sources. Plants closer to
      industrial hotspots showed heavier isotopic compositions (delta66ZnLyon up to
      +0.700/00), indicating significant contributions of fly ash particles, while
      those far away were isotopically light (up to -0.950/00), indicating significant
      contributions from exhaust emissions and flue gas. We suggest that this
      information is applied for improving the environmental and human risk assessment
      related to the exposure to air pollution in urban areas.

PMID- 29320849
TI  - Density Functional Theory Study on the Demethylation Reaction between
      Methylamine, Dimethylamine, Trimethylamine, and Tamoxifen Catalyzed by a Fe(IV)
      Oxo Porphyrin Complex.
AB  - In this work, we studied computationally the N-demethylation reaction of
      methylamine, dimethylamine, and trimethylamine as archetypal examples of primary,
      secondary, and tertiary amines catalyzed by high-field low-spin Fe-containing
      enzymes such as cytochromes P450. Using DFT calculations, we found that the
      expected C-H hydroxylation process was achieved for trimethylamine. When
      dimethylamine and methylamine were studied, two different reaction mechanisms (C
      H hydroxylation and a double hydrogen atom transfer) were computed to be
      energetically accessible and both are equally preferred. Both processes led to
      the formation of formaldehyde and the N-demethylated substrate. Finally, as an
      illustrative example, the relative contribution of the three primary oxidation
      routes of tamoxifen was rationalized through energetic barriers obtained from
      density functional calculations and docking experiments involving CYP3A4 and
      CYP2D6 isoforms. We found that the N-demethylation process was the intrinsically
      favored one, whereas other oxidation reactions required most likely
      preorganization imposed by the residues close to the active sites.

PMID- 29320850
TI  - Uncovering the Origin of Divergence in the CsM(CrO4)2 (M = La, Pr, Nd, Sm, Eu;
      Am) Family through Examination of the Chemical Bonding in a Molecular Cluster and
      by Band Structure Analysis.
AB  - A series of f-block chromates, CsM(CrO4)2 (M = La, Pr, Nd, Sm, Eu; Am), were
      prepared revealing notable differences between the AmIII derivatives and their
      lanthanide analogs. While all compounds form similar layered structures, the
      americium compound exhibits polymorphism and adopts both a structure isomorphous
      with the early lanthanides as well as one that possesses lower symmetry. Both
      polymorphs are dark red and possess band gaps that are smaller than the LnIII
      compounds. In order to probe the origin of these differences, the electronic
      structure of alpha-CsSm(CrO4)2, alpha-CsEu(CrO4)2, and alpha-CsAm(CrO4)2 were
      studied using both a molecular cluster approach featuring hybrid density
      functional theory and QTAIM analysis and by the periodic LDA+GA and LDA+DMFT
      methods. Notably, the covalent contributions to bonding by the f orbitals were
      found to be more than twice as large in the AmIII chromate than in the SmIII and
      EuIII compounds, and even larger in magnitude than the Am-5f spin-orbit splitting
      in this system. Our analysis indicates also that the Am-O covalency in alpha
      CsAm(CrO4)2 is driven by the degeneracy of the 5f and 2p orbitals, and not by
      orbital overlap.

PMID- 29320851
TI  - Stringency of Synthetic Promoter Sequences in Clostridium Revealed and
      Circumvented by Tuning Promoter Library Mutation Rates.
AB  - Collections of characterized promoters of different strengths are key resources
      for synthetic biology, but are not well established for many important organisms,
      including industrially relevant Clostridium spp. When generating promoters,
      reporter constructs are used to measure expression, but classical fluorescent
      reporter proteins are oxygen-dependent and hence inactive in anaerobic bacteria
      like Clostridium. We directly compared oxygen-independent reporters of different
      types in Clostridium acetobutylicum and found that glucuronidase (GusA) from E.
      coli performed best. Using GusA, a library of synthetic promoters was first
      generated by a typical approach entailing complete randomization of a
      constitutive thiolase gene promoter (Pthl) except for the consensus -35 and -10
      elements. In each synthetic promoter, the chance of each degenerate position
      matching Pthl was 25%. Surprisingly, none of the tested synthetic promoters from
      this library were functional in C. acetobutylicum, even though they functioned as
      expected in E. coli. Next, instead of complete randomization, we specified lower
      promoter mutation rates using oligonucleotide primers synthesized using custom
      mixtures of nucleotides. Using these primers, two promoter libraries were
      constructed in which the chance of each degenerate position matching Pthl was 79%
      or 58%, instead of 25% as before. Synthetic promoters from these "stringent"
      libraries functioned well in C. acetobutylicum, covering a wide range of
      strengths. The promoters functioned similarly in the distantly related species
      Clostridium sporogenes, and allowed predictable metabolic engineering of C.
      acetobutylicum for acetoin production. Besides generating the desired promoters
      and demonstrating their useful properties, this work indicates an unexpected
      "stringency" of promoter sequences in Clostridium, not reported previously.

PMID- 29320852
TI  - Exposures to Atmospheric PM10 and PM10-2.5 Affect Male Semen Quality: Results of
      MARHCS Study.
AB  - Studies have shown that the effects of ambient particulate matter (PM) may be
      related to particle's size. However, results on the relationships between
      different PM and reproductive health are controversial. To explore the impacts of
      various PM fractions on male reproductive health, a total of 796 eligible
      subjects recruited in 2013 baseline investigation. In addition, there were 656
      (82.4%) and 568 (71.3%) subjects participated follow-up surveys in 2014 and 2015,
      respectively. We used multivariable regression analysis and mixed-effect model to
      investigate the associations between air pollutants PM10, PM10-2.5, and PM2.5
      exposures and semen quality, sperm DNA fragmentation and serum reproductive
      hormones of subjects. In the preliminary regression analysis, PM10, PM10-2.5, and
      PM2.5 exposure all associated with sperm concentration, morphology, sperm high
      DNA stainability (HDS), serum estradiol and testosterone levels. However, in
      mixed models, we only found that PM10 exposure were negatively associated with
      sperm normal morphology (95% CI: -14.13, -24.47) but positively associated with
      sperm progressive motility (95% CI: 23.00, 8.49), and PM10-2.5 exposure was
      inversely associated with sperm concentration (95% CI: -9.06, -27.31) after
      multiplicity adjustment. Our results provide the evidence that air PM10 and PM10
      2.5 exposures, not PM2.5, are risk factors of semen quality.

PMID- 29320854
TI  - A Highly Resolved Mercury Emission Inventory of Chinese Coal-Fired Power Plants.
AB  - As the largest coal consumer in China, the coal-fired power plants have come
      under increasing public concern in regard to atmospheric mercury pollution. This
      study developed an up-to-date and high-resolution mercury emission inventory of
      Chinese coal-fired power plants using a unit-based method that combined data from
      individual power plants, provincial coal characteristics, and industry removal
      efficiencies. National mercury emissions in 2015 were estimated at 73 tons,
      including 54 tons of elemental mercury, 18 tons of gaseous oxidized mercury and 1
      ton of particle-bound mercury. Pulverized coal boilers emitted 65 tons, mainly in
      the coastal provinces and coal-electricity bases. Circulating fluidized bed
      boilers emitted 8 tons, mainly in Inner Mongolia and Shanxi Province. The average
      mercury emission intensity over the Chinese mainland was 18.3 g/GWh, which was
      similar to the limit for low-rank coal-fired units in the United States. The
      overall uncertainty of national mercury emission was estimated to be -19% to 20%,
      with the mercury content in coal being the major contributor. In most provinces,
      monthly mercury emissions generally peaked in December and August. However,
      monthly partition coefficients of southwest China were obviously lower than other
      regions from June to October due to the high proportion of hydropower generation.

PMID- 29320855
TI  - Sensitive Detection of a Nerve-Agent Simulant through Retightening Internanofiber
      Binding for Fluorescence Enhancement.
AB  - In this work, we develop fluorescent hierarchical nanofiber bundles 1, which
      involve the internanofiber hydrogen-bonding interactions, for rapid and sensitive
      detection of diethyl chlorophosphate (DCP) vapor. First, the internanofiber
      hydrogen-bonding strength can be weakened by photoexcitation, which thereby
      increases the internanofiber spacing and decreases the fluorescence intensity.
      Then, when exposed to trace DCP vapor, the strong interactions between DCP and
      hydroxyl groups on the nanofibers can effectively retighten the nanofibers and
      enhance the fluorescence as the detection signal. In contrast, the interferences,
      such as common organic solvents, cannot retighten nanofiber bundles 1 because of
      the lack of strong interactions with the nanofibers. On the basis of this novel
      detection mechanism, fluorescence detection of DCP with rapid signal response
      (ca. 3 s) and high sensitivity (15 ppb) is achieved.

PMID- 29320853
TI  - High-CO2 Requirement as a Mechanism for the Containment of Genetically Modified
      Cyanobacteria.
AB  - As researchers engineer cyanobacteria for biotechnological applications, we must
      consider potential environmental release of these organisms. Previous theoretical
      work has considered cyanobacterial containment through elimination of the CO2
      concentrating mechanism (CCM) to impose a high-CO2 requirement (HCR), which could
      be provided in the cultivation environment but not in the surroundings. In this
      work, we experimentally implemented an HCR containment mechanism in Synechococcus
      sp. strain PCC7002 (PCC7002) through deletion of carboxysome shell proteins and
      showed that this mechanism contained cyanobacteria in a 5% CO2 environment. We
      considered escape through horizontal gene transfer (HGT) and reduced the risk of
      HGT escape by deleting competence genes. We showed that the HCR containment
      mechanism did not negatively impact the performance of a strain of PCC7002
      engineered for L-lactate production. We showed through coculture experiments of
      HCR strains with ccm-containing strains that this HCR mechanism reduced the
      frequency of escape below the NIH recommended limit for recombinant organisms of
      one escape event in 108 CFU.

PMID- 29320856
TI  - Second-Order Raman Scattering in Exfoliated Black Phosphorus.
AB  - Second-order Raman scattering has been extensively studied in carbon-based
      nanomaterials, for example, nanotube and graphene, because it activates normally
      forbidden Raman modes that are sensitive to crystal disorder, such as defects,
      dopants, strain, and so forth. The sp2-hybridized carbon systems are, however,
      the exception among nanomaterials, where first-order Raman processes usually
      dominate. Here we report the identification of four second-order Raman modes,
      named D1, D1', D2 and D2', in exfoliated black phosphorus (P(black)), an
      elemental direct-gap semiconductor exhibiting strong mechanical and electronic
      anisotropies. Located in close proximity to the Ag1 and Ag2 modes, these new
      modes dominate at an excitation wavelength of 633 nm. Their evolutions as a
      function of sample thickness, excitation wavelength, and defect density indicate
      that they are defect-activated and involve high-momentum phonons in a doubly
      resonant Raman process. Ab initio simulations of a monolayer reveal that the D'
      and D modes occur through intravalley scatterings with split contributions in the
      armchair and zigzag directions, respectively. The high sensitivity of these D
      modes to disorder helps explaining several discrepancies found in the literature.

PMID- 29320857
TI  - Microhydration of 2-Naphthol at Ground, First Excited Triplet, and First Excited
      Singlet States: A Case Study on Photo Acids.
AB  - Molecular interactions of 2-naphthol (nap) with water molecules are studied at
      the ground, first excited triplet and first excited singlet states, applying DFT
      and TD-DFT methods. The minimum energy structure of hydrated clusters of 2
      naphthol up to four water molecules are selected from several possible input
      geometries. It is observed that the minimum energy conformer of the tetra-hydrate
      of 2-naphthol has proton transfer occurring from nap to solvent water molecules,
      in its first excited singlet state. This is however not observed in case of its
      ground or first excited triplet state. It is consistent with the fact that the
      pKa of nap in the first excited singlet state is very much lower compared to the
      ground and first excited triplet state. This is also reflected in the O-H
      potential energy profile of tetrahydrate of nap, obtained by performing a rigid
      potential energy scan of the dissociating O-H bond of nap at ground, first
      excited triplet and first excited singlet states. Frequency of O-H stretching
      vibration of 2-napthol and its hydrated clusters in the ground (S0) as well as in
      the first excited singlet (S1) state are calculated and compared with the
      available experimental data. The performance of macroscopic solvation model is
      also examined in the ground and these excited states.

PMID- 29320858
TI  - Editorial for January 2018 for JPC A/B/C.

PMID- 29320859
TI  - Editorial for January 2018 for JPC A/B/C.

PMID- 29320860
TI  - Time-of-flight secondary ion mass spectrometry analyses of vancomycin.
AB  - As an antibiotic that prevents and treats infections caused by Gram-positive
      bacteria such as Staphylococcus aureus, vancomycin incorporated in a
      biodegradable polymer poly(lactide-co-glycolide) provides opportunities to
      construct controlled-release drug delivery systems. Developments associated with
      this promising system have been largely concentrated on areas of drug delivery
      kinetics and biodegradability. In order to provide surface analytical approaches
      to this important system, the authors demonstrate applicability of time-of-flight
      secondary ion mass spectrometry (TOF-SIMS) in three-dimensional molecular imaging
      for a model system consisting of alternating layers of ploy(lactide-co-glycolide)
      and vancomycin. TOF-SIMS imaging clarified that the two chemicals can undergo
      phase separation when dimethyl sulfoxide is used as the solvent. The authors
      identified two diagnostic ions that are abundant and structural moieties of
      vancomycin. The results on TOF-SIMS imaging and depth profiling vancomycin
      provide useful information for further applications of TOF-SIMS in the
      development of antibiotic drug delivery systems involving the use of vancomycin.

PMID- 29320861
TI  - 3D echoendoscopy and miniprobes for rectal cancer staging.
AB  - BACKGROUND: rectal cancer staging using rigid probes or echoendoscopes has some
      limitations. The aim of the study was to compare rectal cancer preoperative
      staging using conventional endoluminal ultrasonography with three-dimensional
      endoscopic ultrasonography and miniprobes. MATERIALS AND METHODS: sixty patients
      were included and evaluated with: a) a conventional echoendoscope (7.5 and 12
      MHz); b) miniprobes (12 MHz); and c) the Easy 3D Freescan software for three
      dimensional endoscopic ultrasonography. The reference or gold standard was
      conventional endoluminal ultrasonography in all cases and pathological assessment
      for those without preoperative therapy. The differences in T and N staging
      accuracy in both longitudinal and circumferential extension were evaluated.
      RESULTS: with regard to T staging, conventional endoluminal ultrasonography had
      an accuracy of 85% (compared to pathological analysis), and the agreement between
      miniprobes vs conventional endoluminal ultrasonography (kappa = 0.81) and three
      dimensional endoscopic ultrasonography vs conventional endoluminal
      ultrasonography (k = 0.87) was significant. In addition, miniprobes had an
      accuracy of 82% and three-dimensional endoscopic ultrasonography had a higher
      accuracy (96%). With regard to N staging, conventional endoluminal
      ultrasonography had an accuracy of 91% with a sensitivity of 78%. However, the
      agreement between miniprobes and conventional endoluminal ultrasonography and
      three-dimensional endoscopic ultrasonography and conventional endoluminal
      ultrasonography (k = 0.70) was lower. Interestingly, miniprobes had a lower
      accuracy of 81% whereas three-dimensional endoscopic ultrasonography had an
      accuracy of 100% without any false negative. No false positives were observed in
      any of the techniques. Accuracy for T and N staging was not influenced by
      longitudinal or circumferential extensions of the tumor in all types of
      endoscopic ultrasonography analyzed. CONCLUSIONS: miniprobes and especially three
      dimensional endoscopic ultrasonography may be relevant during rectal cancer
      staging.

PMID- 29320862
TI  - Inter and intra-observer concordance for the diagnosis of portal hypertension
      gastropathy.
AB  - INTRODUCTION: At present there is no fully accepted endoscopic classification for
      the assessment of the severity of portal hypertensive gastropathy (PHG). Few
      studies have evaluated inter and intra-observer concordance or the degree of
      concordance between different endoscopic classifications. OBJECTIVES: To evaluate
      inter and intra-observer agreement for the presence of portal hypertensive
      gastropathy and enteropathy using different endoscopic classifications. METHODS:
      Patients with liver cirrhosis were included into the study. Enteroscopy was
      performed under sedation. The location of lesions and their severity was
      recorded. Images were videotaped and subsequently evaluated independently by
      three different endoscopists, one of whom was the initial endoscopist. The
      agreement between observations was assessed using the kappa index. RESULTS:
      Seventy-four patients (mean age 63.2 years, 53 males and 21 females) were
      included. The agreement between the three endoscopists regarding the presence or
      absence of PHG using the Tanoue and McCormack classifications was very low (kappa
      scores = 0.16 and 0.27, respectively). CONCLUSIONS: The current classifications
      of portal hypertensive gastropathy have a very low degree of intra and inter
      observer agreement for the diagnosis and assessment of gastropathy severity.

PMID- 29320863
TI  - Evaluation of an iterative model-based CT reconstruction algorithm by intra
      patient comparison of standard and ultra-low-dose examinations.
AB  - Background The explosive growth of computer tomography (CT) has led to a growing
      public health concern about patient and population radiation dose. A recently
      introduced technique for dose reduction, which can be combined with tube-current
      modulation, over-beam reduction, and organ-specific dose reduction, is iterative
      reconstruction (IR). Purpose To evaluate the quality, at different radiation dose
      levels, of three reconstruction algorithms for diagnostics of patients with
      proven liver metastases under tumor follow-up. Material and Methods A total of 40
      thorax-abdomen-pelvis CT examinations acquired from 20 patients in a tumor follow
      up were included. All patients were imaged using the standard-dose and a specific
      low-dose CT protocol. Reconstructed slices were generated by using three
      different reconstruction algorithms: a classical filtered back projection (FBP);
      a first-generation iterative noise-reduction algorithm (iDose4); and a next
      generation model-based IR algorithm (IMR). Results The overall detection of liver
      lesions tended to be higher with the IMR algorithm than with FBP or iDose4. The
      IMR dataset at standard dose yielded the highest overall detectability, while the
      low-dose FBP dataset showed the lowest detectability. For the low-dose protocols,
      a significantly improved detectability of the liver lesion can be reported
      compared to FBP or iDose4 ( P = 0.01). The radiation dose decreased by an
      approximate factor of 5 between the standard-dose and the low-dose protocol.
      Conclusion The latest generation of IR algorithms significantly improved the
      diagnostic image quality and provided virtually noise-free images for ultra-low
      dose CT imaging.

PMID- 29320864
TI  - Diagnostic performance of static single-scan stress perfusion cardiac computed
      tomography in detecting hemodynamically significant coronary artery stenosis: a
      comparison with combined invasive coronary angiography and cardiovascular
      magnetic resonance-myocardial perfusion imaging.
AB  - Background Non-invasive anatomical and physiological evaluations of coronary
      artery disease (CAD) may be obtained with static single-scan stress perfusion
      cardiac computed tomography (SSPCT). Purpose To determine the diagnostic
      performance of static SSPCT for identifying hemodynamically significant CAD.
      Material and Methods This prospective study included 29 patients with suspected
      or known CAD who underwent static SSPCT, cardiovascular magnetic resonance
      myocardial perfusion imaging (CMR-MPI), and invasive coronary angiography (ICA).
      CT was performed as follows: (i) coronary calcium scan; (ii) static SSPCT for
      both coronary artery (coronary CT angiography [CCTA]) and myocardial perfusion
      (perfusion CT [PCT]) during adenosine infusion; (iii) late-phase scan. The
      diagnostic performance of CCTA alone, PCT alone, and SSPCT for the detection of a
      hemodynamically significant CAD (a perfusion defect in a vascular territory
      subtended by a coronary vessel with >= 50% stenosis) was compared with that of
      combined ICA/CMR-MPI representing the standard of reference. Results Twenty-three
      (79%) patients and 47 (54%) vascular territories manifested ischemia-causing
      coronary stenoses by combined ICA/CMR-MPI. The per-vessel sensitivity,
      specificity, positive and negative predictive values, and area under the receiver
      operating characteristic curve (AUC) of the SSPCT were 92%, 88%, 90%, 90%, and
      0.90, respectively, compared to those of the combined ICA/CMR-MPI. These values
      for the CCTA alone were 96%, 63%, 75%, 93%, and 0.79, respectively; and the
      values for the PCT alone were 94%, 83%, 86%, 92%, and 0.88, respectively. The AUC
      of SSPCT was significantly ( P = 0.013) higher than that of the CCTA alone.
      Conclusion Static SSPCT may facilitate detection of hemodynamically significant
      CAD.

PMID- 29320866
TI  - Paradigm shift in psychiatry: what may it involve?
AB  - OBJECTIVE: This study aims to examine the potential nature of an ongoing paradigm
      shift in psychiatry that has been suggested to be occurring. CONCLUSIONS: New
      findings in traumatology and neuroscience do form a potential platform for a
      paradigm shift. Prior conflicting paradigms are suggested to be due to biases
      arising from mental structures themselves. A new wholist perspective is proposed,
      which makes sense of and incorporates previous paradigms, and coheres recent
      understanding of right- and left-brain functioning and biopsychosocial traumatic
      processes and their ramifications. The perspective makes sense of the great
      variety of post-traumatic manifestations ranging from somatic to meaning-making
      dysfunctions. The wholist perspective may well be an important step in
      solidifying a fresh paradigmatic perspective in psychiatry.

PMID- 29320870
TI  - Transgenic Organisms Meet Redox Bioimaging: One Step Closer to Physiology.
AB  - SIGNIFICANCE: Redox signaling is a common mechanism in the cellular response
      toward a variety of stimuli. For analyzing redox-dependent specific alterations
      in a cell, genetically encoded biosensors were highly instrumental in the past.
      To advance the knowledge about the importance of this signaling mechanism in
      vivo, models that are as close as possible to physiology are needed. Recent
      Advances: The development of transgenic (tg) redox biosensor animal models has
      enhanced the knowledge of redox signaling under patho(physio)logical conditions.
      So far, commonly used small animal models, that is, Caenorhabditis elegans,
      Drosophila melanogaster, and Danio rerio, and genetically modified mice were
      employed for redox biosensor transgenesis. However, especially the available
      mouse models are still limited. CRITICAL ISSUES: The analysis of redox biosensor
      responses in vivo at the tissue level, especially for internal organs, is
      hampered by the detection limit of the available redox biosensors and microscopy
      techniques. Recent technical developments such as redox histology and the
      analysis of cell-type-specific biosensor responses need to be further refined and
      followed up in a systematic manner. FUTURE DIRECTIONS: The usage of tg animal
      models in the field of redox signaling has helped to answer open questions.
      Application of the already established models and consequent development of more
      defined tg models will enable this research area to define the role of redox
      signaling in (patho)physiology in further depth. Antioxid. Redox Signal. 29, 603
      612.

PMID- 29320871
TI  - Can the mental health of Australians be improved by dual strategy for promotion
      and prevention?

PMID- 29320872
TI  - Correction to: Bai et al., Melatonin promotes self-renewal of nestin-positive
      pancreatic stem cells through activation of the MT2/ERK/SMAD/nestin axis.

PMID- 29320873
TI  - Does progressive nuclear staining with hemalum (alum hematoxylin) involve DNA,
      and what is the nature of the dye-chromatin complex?
AB  - Previous investigators have disagreed about whether hemalum stains DNA or its
      associated nucleoproteins. I review here the literature and describe new
      experiments in an attempt to resolve the controversy. Hemalum solutions, which
      contain aluminum ions and hematein, are routinely used to stain nuclei. A
      solution containing 16 Al3+ ions for each hematein molecule, at pH 2.0-2.5,
      provides selective progressive staining of chromatin without cytoplasmic or
      extracellular "background color." Such solutions contain a red cationic dye-metal
      complex and an excess of Al3+ ions. The red complex is converted to an insoluble
      blue compound, assumed to be polymeric, but of undetermined composition, when
      stained sections are blued in water at pH 5.5-8.5. Staining experiments with DNA,
      histone and DNA + histone mixtures support the theory that DNA, not histone, is
      progressively colored by hemalum. Extraction of nucleic acids, by either a strong
      acid or nucleases at near neutral pH, prevented chromatin staining by a simple
      cationic dye, thionine, pH 4, and by hemalum, with pH adjustments in the range,
      2.0-3.5. Staining by hemalum at pH 2.0-3.5 was not inhibited by methylation,
      which completely prevented staining by thionine at pH 4. Staining by hemalum and
      other dye-metal complexes at pH <= 2 may be due to the high acidity of DNA
      phosphodiester (pKa ~ 1). This argument does not explain the requirement for a
      much higher pH to stain DNA with those dyes and fluorochromes not used as dye
      metal complexes. Sequential treatment of sections with Al2(SO4)3 followed by
      hematein provides nuclear staining that is weaker than that attainable with
      hemalum. Stronger staining is seen if the pH is raised to 3.0-3.5, but there is
      also coloration of cytoplasm and other materials. These observations do not
      support the theory that Al3+ forms bridges between chromatin and hematein. When
      staining with hematein is followed by an Al2(SO4)3 solution, there is no
      significant staining. Taken together, the results of my study indicate that the
      red hemalum cation is electrostatically attracted to the phosphate anion of DNA.
      The bulky complex cation is too large to intercalate between base pairs of DNA
      and is unlikely to fit into the minor groove. The short range van der Waals
      forces that bind planar dye cations to DNA probably do not contribute to the
      stability of progressive hemalum staining. The red cation is precipitated in situ
      as a blue compound, insoluble in water, ethanol and water-ethanol mixtures, when
      a stained preparation is blued at pH > 5.5.

PMID- 29320869
TI  - Challenges and Opportunities for Small-Molecule Fluorescent Probes in Redox
      Biology Applications.
AB  - SIGNIFICANCE: The concentrations of reactive oxygen/nitrogen species (ROS/RNS)
      are critical to various biochemical processes. Small-molecule fluorescent probes
      have been widely used to detect and/or quantify ROS/RNS in many redox biology
      studies and serve as an important complementary to protein-based sensors with
      unique applications. Recent Advances: New sensing reactions have emerged in probe
      development, allowing more selective and quantitative detection of ROS/RNS,
      especially in live cells. Improvements have been made in sensing reactions,
      fluorophores, and bioavailability of probe molecules. CRITICAL ISSUES: In this
      review, we will not only summarize redox-related small-molecule fluorescent
      probes but also lay out the challenges of designing probes to help redox
      biologists independently evaluate the quality of reported small-molecule
      fluorescent probes, especially in the chemistry literature. We specifically
      highlight the advantages of reversibility in sensing reactions and its
      applications in ratiometric probe design for quantitative measurements in living
      cells. In addition, we compare the advantages and disadvantages of small-molecule
      probes and protein-based probes. FUTURE DIRECTIONS: The low physiological
      relevant concentrations of most ROS/RNS call for new sensing reactions with
      better selectivity, kinetics, and reversibility; fluorophores with high quantum
      yield, wide wavelength coverage, and Stokes shifts; and structural design with
      good aqueous solubility, membrane permeability, low protein interference, and
      organelle specificity. Antioxid. Redox Signal. 29, 518-540.

PMID- 29320874
TI  - German Version of the Inventory of Motivations for Hospice Palliative Care
      Volunteerism: Are There Gender Differences?
AB  - The present study examined gender differences in motivations for volunteering for
      hospice using a German version of the Inventory of Motivations for Hospice
      Palliative Care Volunteerism (IMHPCV). The IMHPCV was translated into German and
      back-translated into English following the World Health Organization's guidelines
      for the translation and adaptation of instruments. In an online survey, 599
      female and 127 male hospice volunteers from hospice organizations throughout
      Germany completed the translated version of the IMHPCV, the Scales of the
      Attitude Structure of Volunteers as well as questions pertaining to their
      volunteer experience. Based on an exploratory structural equation modeling
      approach, adequate model fit was found for the expected factor structure of the
      German version of the IMHPCV. The IMHPCV showed adequate internal consistency and
      construct validity. Both female and male hospice volunteers found altruistic
      motives and humanitarian concerns most influential in their decision to volunteer
      for hospice. Personal gain was least influential. Men rated self-promotion, civic
      responsibility, and leisure as more important than women. Analyses provided
      support for the use of the IMHPCV as a measurement tool to assess motivations to
      volunteer for hospice. Implications for recruitment and retention of hospice
      volunteers, in particular males, are given.

PMID- 29320875
TI  - Characterization of bacteriophages and their carriage in Staphylococcus aureus
      isolated from broilers in Poland.
AB  - 1. The objective of this study was the isolation and morphological
      characterization of temperate bacteriophages induced from Staphylococcus aureus
      strains isolated from clinical samples from broiler chickens and turkeys. 2.
      Eighty-five S. aureus strains were tested for susceptibility to oxacillin in
      order to determine which were methicillin resistant (MRSA). A total of 24 strains
      showed resistance to methicillin. 3. Thirty-one bacteriophages that were lytic
      against S. aureus strains were isolated and the host range of the bacteriophages
      was evaluated. Based on the presence of a specific nucleotide sequence, molecular
      identification of bacteriophages was performed and the presence of genes
      responsible for the production of classical enterotoxins (A-E) was also analysed.
      4. All the isolated bacteriophages had an icosahedral head and a long, thin, non
      contractile flexible tail, characteristic of the family Siphoviridae of the order
      Caudovirales. Based on multiplex PCR results, the phages were found to belong to
      serogroups A, B and F (Fa, Fb subgroup), which include mostly temperate phages
      infecting S. aureus. 5. The titre of the phages ranged from 10-4 to 10-9 PFU/ml.
      The bacteriophages exhibited strong lytic properties against some of the strains
      of Staphylococcus. The broadest spectrum of activity against the strains was
      observed in the case of phages sa2, sa3, sa6, sa12, sa15 and sa21. 6. The PCR
      results showed that of the 31 bacteriophage DNA samples, 4 (12.9%) appeared to
      have enterotoxigenic genes.

PMID- 29320876
TI  - "It's not really worth my while": understanding contextual factors contributing
      to decisions to participate in community aphasia groups.
AB  - PURPOSE: Community aphasia groups represent a formalised opportunity for social
      participation. The potential barriers and facilitators to accessing and
      maintaining group participation remain poorly understood. The aim of this study
      was to explore environmental and personal factors contributing to community
      aphasia group participation. METHODS: A framework analysis (FA) was used to
      analyse the semi-structured interview data from 22 current and past members of
      community aphasia groups. RESULTS: People with aphasia weigh up the benefits of
      group participation in the context of a range of personal and environmental
      factors. These include personal coping mechanisms, perceptions of existing social
      support as well as the practicalities of accessing the group. CONCLUSIONS:
      Understanding factors that contribute to participation experiences is critical to
      ensure that, people with aphasia are well supported to access and engage in
      community aphasia groups. This study found that people may be more able to
      participate when they are accepting of the chronic nature of the aphasia, when
      they identify tangible benefits to participation, and when they have easy access
      to the group. This suggests a role for speech pathologists to recognise critical
      periods of need and support people with aphasia and their significant others to
      access and engage in group services. Implications for Rehabilitation Critical
      stages exist when people with aphasia may feel more ready and able to participate
      in community aphasia groups. These critical stages include an acceptance of the
      chronic nature of aphasia, as well as a desire to make positive change. There is
      a need for clinicians to minimise barriers to participation early in the
      therapeutic relationship. Proliferation of community aphasia groups will function
      to alleviate environmental barriers associated with poor public awareness of
      groups and group accessibility.

PMID- 29320877
TI  - "I'm still me - I'm still here!" Understanding the person's sense of self in the
      provision of self-management support for people with progressive neurological
      long-term conditions.
AB  - PURPOSE: There is increasing interest in tailoring self-management support, but
      little detail is available on the relevance and impact of such approaches for
      people with progressive neurological conditions. The aim of this study was to
      draw on individuals' experiences to inform the practice of self-management
      support for these groups. METHOD: Community rehabilitation service users were
      purposively recruited and took part in in-depth qualitative interviews.
      Interviews were audio-recorded and transcribed. Data analysis was iterative and
      interpretative, taking a phenomenological approach. Strategies to enhance rigor
      were auditability, peer review, and researcher reflexivity. RESULTS: The sample
      consisted of 10 adults (age 20-79 years) who were living with a range of
      progressive neurological conditions. Individuals demonstrated resourcefulness in
      developing practice-based self-management strategies. Beyond practical
      strategies, interviewees' experiences were signified by reflecting on and
      upholding a sense of identity and a desire for purpose against the background of
      losses and gains over time. Linking with this overarching theme of "Sense of
      self" were aspects of "My body and mind", "Time", "Space", "Relationships", and
      "What I do". CONCLUSIONS: Self-management approaches for individuals with
      progressive neurological conditions will benefit from incorporating ways of
      recognizing, articulating, and supporting the person's sense of identity and
      purpose. Implications for rehabilitation Self-management approaches for people
      with progressive neurological conditions need to take account of individuals'
      wishes to contribute, connect with others, and be valued as a person. Person
      centred self-management support can be realized through a broader approach than
      solely managing disease progression. The experiences and words of people with
      progressive neurological conditions can be used to inform meaningful evaluation
      of self-management support to drive service delivery by measuring what really
      matters. Rehabilitation practitioners need to adapt their conceptualisations of
      goal setting to account for how people with progressive neurological conditions
      themselves interpret "progress" and "improvement". Person-centred conversation
      that values who the person is can be an effective starting point for self
      management interventions in people with progressive neurological conditions.

PMID- 29320878
TI  - Exercise training for improving outcomes post-burns: a systematic review and meta
      analysis.
AB  - OBJECTIVES: To determine the effectiveness of different modalities of exercise
      and to evaluate the safety of exercise-based interventions post-burns. DATA
      SOURCES: Six databases were searched from inception to October 2017 using "burn,"
      "exercise" and synonyms as keywords. Relevant authors, key journals and reference
      lists of included studies were hand-searched. REVIEW METHODS: Articles reporting
      on exercise interventions in patients post-burn and considering physical,
      physiological or psychological outcomes were considered. Two authors
      independently screened 2253 records and selected 19 articles for inclusion. The
      quality of the evidence was assessed at the study level and at the outcome level.
      RESULTS: Unbiased effect size estimators (pooled Hedges' g) with 95% confidence
      intervals (CIs) were calculated if there were two or more trials with homogeneous
      outcomes. There were no significant differences post-exercise training in VO2peak
      ( g = 0.99; 95% CI: -0.4 to 2.4: P = 0.18), resting energy expenditure ( g = 
      0.51; 95% CI: -1.99 to 0.97: P = 0.5) and muscle strength ( g = 0.51; 95% CI: 
      0.03 to 1.05: P = 0.07) between groups. Evidence suggested exercise had a
      beneficial effect on body composition ( g = 0.59; 95% CI: 0.05 to 1.14: P =
      0.03), need of surgical release of contractures (risk ratio = 0.34; 95% CI: 0.2
      to 0.7; P = 0.004) and health-related quality of life. However, a lack of
      evidence existed regarding the safety of exercise training post-burns.
      CONCLUSION: Limited evidence suggests that exercise has a beneficial effect on
      physical and physiological outcomes in patients post-burn. Further trials using
      high-quality methodology are required, with focus on reporting of adverse events,
      health-related quality of life and psychological outcomes.

PMID- 29320879
TI  - Isolation and purification of diterpenoids from the aerial parts of Isodon
      excisoides target-guided by UPLC-LTQ-Orbitrap-MS.
AB  - Cytotoxic diterpenoids were enriched and orientation prepared from the aerial
      parts of Isodon excisoides target-guided by UPLC-LTQ-Orbitrap-MS. Four
      diterpenoids were obtained, including a novel compound: 1alpha-acetoxy-7alpha,
      14beta, 20alpha-trihydroxy-ent-kaur-16-en-15-one (1); together with three known
      compounds kamebakaurin (2), lasiokaurin (3), enmenol-1-beta-glucoside (4). Their
      structures were elucidated on the basis of spectroscopic methods in conjunction
      with published data for their analogues. All compounds were tested for their
      cytotoxic effects against five human cancer cell lines HCT-116, HepG2, A2780, NCI
      H1650 and BGC-823, respectively. Compounds 1 and 2 showed obviously cytotoxic
      activity against the five cancer cell lines with IC50 ranging from 1.06 to 3.60
      MUM. Compounds 3 and 4 showed selective cytotoxic activity.

PMID- 29320880
TI  - Gas-phase relative stabilities of Tl+-crown ether complexes and Rb+-crown ether
      complexes.
AB  - The gas-phase stabilities of Tl+-crown ether complexes and Rb+-crown ether
      complexes were studied using the electrospray ionization-collision-induced
      dissociation-tandem mass spectrometry. Tl+ and Rb+ have identical ionic radii,
      thus a comparison of the properties of the crown ether complexes with these two
      cations seems to be justified. The selected crown ethers were 12C4 (it has a
      cavity smaller than the cation radius), 18C6 (it has a cavity of size similar to
      the cation radius), 24C8 (it has a cavity greater than the cation radius) and
      their conjugates. It has been found that the crown ether complexes of
      stoichiometry 1:1 with Tl+ are more or equally stable in the gas phase than the
      crown ether complexes with Rb+. However, 2:1 complexes with Tl+ are less stable
      than the complexes with Rb+.

PMID- 29320881
TI  - Masculinity and preventing falls: insights from the fall experiences of men aged
      70 years and over.
AB  - PURPOSE: To explore men's fall experiences through the lens of masculine
      identities so as to assist health professionals better engage men in fall
      prevention programs. METHODS: Twenty-five men, aged 70-93 years who had
      experienced a recent fall, participated in a qualitative semi-structured
      interview. Men's willingness to engage in fall prevention programs taking account
      of individual contexts and expressions of masculinity, were conceptualised using
      constant comparative methods. RESULTS: Men's willingness to engage in fall
      prevention programs was related to their perceptions of the preventability of
      falls; personal relevance of falls; and age, health, and capability as well as
      problem-solving styles to prevent falls. Fall prevention advice was rarely given
      when men accessed the health system at the time of a fall. CONCLUSIONS: Contrary
      to dominant expectations about masculine identity, many men acknowledged fall
      vulnerability indicating they would attend or consider attending, a fall
      prevention program. Health professionals can better engage men by providing
      consistent messages that falls can be prevented; tailoring advice, understanding
      men are at different stages in their awareness of fall risk and preferences for
      action; and by being aware of their own assumptions that can act as barriers to
      speaking with men about fall prevention. Implications for rehabilitation Men
      accessing the health system at the time of the fall, and during rehabilitation
      following a fall represent prime opportunities for health professionals to speak
      with men about preventing falls and make appropriate referrals to community
      programs. Tailored advice will take account of individual men's perceptions of
      preventability; personal relevance; perceptions of age, health and capability;
      and problem-solving styles.

PMID- 29320882
TI  - The impact of influenza virus infection in pregnancy.
AB  - Data from previous seasonal epidemics and pandemics have confirmed that pregnant
      women are at increased risk for severe influenza virus infection. Complications
      including fetal loss, higher rates of hospitalization and maternal death are most
      notable during the late gestational period. Antiviral therapy and influenza
      vaccination are recommended in pregnant women as both are effective and safe.
      This review discusses the epidemiology, pathophysiology, treatment and prevention
      of influenza virus infection in pregnancy, with a focus on recent developments.

PMID- 29320883
TI  - The prevalence of oral stage dysphagia in adults presenting with
      temporomandibular disorders: a systematic review and meta-analysis.
AB  - OBJECTIVE: Temporomandibular disorders (TMDs) are the most commonly experienced
      non-dental orofacial pain disorders, with pain and dysfunction potentially
      resulting in oral stage dysphagia (OD). However, limited research has been
      conducted on this condition, with potential negative effects on clinical
      practice. Therefore, the aim of this study was to determine the prevalence of OD
      in adults presenting with TMDs, diagnosed as per the Research Diagnostic Criteria
      for Temporomandibular Disorders or the Diagnostic Criteria for Temporomandibular
      Disorders protocols. MATERIAL AND METHODS: A systematic review of the literature
      was completed. Nine electronic databases were searched from inception to January
      2017, with no date/language restriction applied. Grey literature, conference
      proceedings, and reference lists were also searched. Studies presenting original
      data regarding OD prevalence in adults presenting with TMDs were included if they
      investigated impaired swallowing, mastication, masticatory pain or fatigue, or
      weight loss. Study eligibility and quality were assessed by two independent
      reviewers. Methodological quality was assessed using the Down's and Black tool.
      RESULTS AND CONCLUSIONS: This search yielded 20 eligible studies. Swallowing
      itself was impaired in only 9.3% of patients with TMDs. A range of additional OD
      signs and symptoms were also commonly reported (e.g. masticatory pain (87.4%) and
      fatigue (62%)). Study limitations included the small number of studies which were
      eligible for inclusion. As signs and symptoms of OD are frequently reported by
      patients with TMDs, psychometrically robust prospective research is warranted to
      determine current and optimal management of this condition.

PMID- 29320884
TI  - Correlation Between Third Trimester Glycemic Variability in Non-Insulin-Dependent
      Gestational Diabetes Mellitus and Adverse Pregnancy and Fetal Outcomes.
AB  - BACKGROUND: Gestational diabetes mellitus (GDM) is a pregnancy-related metabolic
      complication. Despite optimal glycemic control from self-monitoring blood glucose
      (SMBG) in non-insulin-dependent GDM, variations in pregnancy outcomes persist.
      Glycemic variability is believed to be a factor that causes adverse pregnancy
      outcomes. Continuous glucose monitoring system (CGMS) detects interstitial
      glucose values every 5 minutes, and glycemic variability data from CGMS during
      the third trimester may be a predictor of fetal birth weight and pregnancy
      outcomes. The aim of this study was to investigate correlation between third
      trimester glycemic variability in non-insulin-dependent GDM and fetal birth
      weight. METHOD: This prospective study was conducted in 55 pregnant volunteers
      with non-insulin-dependent GDM that were recruited at 28 to 32 weeks' gestation
      from the outpatient clinic of the Department of Obstetrics and Gynecology,
      Faculty of Medicine Siriraj Hospital during the study period of August 1 to
      December 31, 2016. Patients had CGMS installed for at least 72 hours and glycemic
      variability data were analyzed. RESULTS: Of 55 enrolled volunteers, the data from
      47 women were included in the analysis. Mean CGMS duration was 85.5 +/- 12.83
      hours. No statistically significant correlation was identified between glycemic
      variability in third trimester and birth weight percentiles, or between third
      trimester CGMS parameters and pregnancy outcomes in the study. CONCLUSION: Based
      on these findings, third trimester glycemic variability data from CGMS are not a
      predictor of fetal birth weight percentile, and no significant association was
      found between CGMS parameters and adverse pregnancy outcomes; thus, CGMS is not
      necessary in non-insulin-dependent GDM.

PMID- 29320885
TI  - A Pilot Study Validating Select Research-Grade and Consumer-Based Wearables
      Throughout a Range of Dynamic Exercise Intensities in Persons With and Without
      Type 1 Diabetes: A Novel Approach.
AB  - BACKGROUND: The increasing popularity of wearable technology necessitates the
      evaluation of their accuracy to differentiate physical activity (PA) intensities.
      These devices may play an integral role in customizing PA interventions for
      primary prevention and secondary management of chronic diseases. For example, in
      persons with type 1 diabetes (T1D), PA greatly affects glucose concentrations
      depending on the intensity, mode (ie, aerobic, anaerobic, mixed), and duration.
      This variability in glucose responses underscores the importance of implementing
      dependable wearable technology in emerging avenues such as artificial pancreas
      systems. METHODS: Participants completed three 40-minute, dynamic non-steady
      state exercise sessions, while outfitted with multiple research (Fitmate, Metria,
      Bioharness) and consumer (Garmin, Fitbit) grade wearables. The data were
      extracted according to the devices' maximum sensitivity (eg, breath by breath,
      beat to beat, or minute time stamps) and averaged into minute-by-minute data. The
      variables of interest, heart rate (HR), breathing frequency, and energy
      expenditure (EE), were compared to validated criterion measures. RESULTS:
      Compared to deriving EE by laboratory indirect calorimetry standard, the Metria
      activity patch overestimates EE during light-to-moderate PA intensities (L-MI)
      and moderate-to-vigorous PA intensities (M-VI) (mean +/- SD) (0.28 +/- 1.62
      kilocalories. minute-1, P < .001, 0.64 +/- 1.65 kilocalories. minute-1, P < .001,
      respectively). The Metria underestimates EE during vigorous-to-maximal PA
      intensity (V-MI) (-1.78 +/- 2.77 kilocalories . minute-1, P < .001). Similarly,
      compared to Polar HR monitor, the Bioharness underestimates HR at L-MI (-1 +/- 8
      bpm, P < .001) and M-VI (5 +/- 11 bpm, P < .001), respectively. A significant
      difference in EE was observed for the Garmin device, compared to the Fitmate ( P
      < .001) during continuous L-MI activity. CONCLUSIONS: Overall, our study
      demonstrates that current research-grade wearable technologies operate within a
      ~10% error for both HR and EE during a wide range of dynamic exercise
      intensities. This level of accuracy for emerging research-grade instruments is
      considered both clinically and practically acceptable for research-based or
      consumer use. In conclusion, research-grade wearable technology that uses EE
      kilocalories . minute-1 and HR reliably differentiates PA intensities.

PMID- 29320886
TI  - Contribution of preventive methods in controlling caries among Saudi primary
      schoolchildren: a population-based cross-sectional study.
AB  - OBJECTIVE: This study assessed the association between caries preventive measures
      including regular dental checkups, twice a day tooth brushing using fluoridated
      toothpaste and pit and fissure sealants on one side and the presence of caries
      among primary schoolchildren in the Eastern Province of Saudi Arabia. MATERIALS
      AND METHODS: A cross-sectional study was conducted in 2016 including 1198, 6-12
      year-old children from 13 randomly selected schools. The outcome variable was
      caries presence. The explanatory variables were brushing twice a day using
      fluoridated toothpaste, the presence of sealant and regular dental checkups.
      Multivariable logistic regression model was conducted to assess the associations
      controlling for confounders (age, gender, ability to get treatment, being health
      insured and school) using SPSS version 20.0. RESULTS: Data of 921 participants
      (83.8%) were available. The prevalence of caries was 63.5%, whereas 67.6% brushed
      their teeth twice a day, 28.3% visited the dentist for regular checkups and 7.6%
      had sealant. In multivariable regression, out of the three main explanatory
      variables, only having regular checkups was significantly associated with caries
      presence (OR = 0.65, 95% CI = 0.48, 0.88). CONCLUSIONS: Lower odds of caries
      presence were associated with regular dental checkups but not with regular
      brushing or having sealant.

PMID- 29320887
TI  - Transducing Airway Basal Cells with a Helper-Dependent Adenoviral Vector for Lung
      Gene Therapy.
AB  - A major challenge in developing gene-based therapies for airway diseases such as
      cystic fibrosis (CF) is sustaining therapeutic levels of transgene expression
      over time. This is largely due to airway epithelial cell turnover and the host
      immunogenicity to gene delivery vectors. Modern gene editing tools and delivery
      vehicles hold great potential for overcoming this challenge. There is currently
      not much known about how to deliver genes into airway stem cells, of which basal
      cells are the major type in human airways. In this study, helper-dependent
      adenoviral (HD-Ad) vectors were delivered to mouse and pig airways via intranasal
      delivery, and direct bronchoscopic instillation, respectively. Vector
      transduction was assessed by immunostaining of lung tissue sections, which
      revealed that airway basal cells of mice and pigs can be targeted in vivo. In
      addition, efficient transduction of primary human airway basal cells was verified
      with an HD-Ad vector expressing green fluorescent protein. Furthermore, we
      successfully delivered the human CFTR gene to airway basal cells from CF
      patients, and demonstrated restoration of CFTR channel activity following cell
      differentiation in air-liquid interface culture. Our results provide a strong
      rationale for utilizing HD-Ad vectors to target airway basal cells for permanent
      gene correction of genetic airway diseases.

PMID- 29320888
TI  - Comparative studies with EPR and MRI on the in vivo tissue redox status
      estimation using redox-sensitive nitroxyl probes: influence of the choice of the
      region of interest.
AB  - In vivo decay rates of a nitroxyl contrast agent were estimated by a MR redox
      imaging (MRRI) technique and compared with the decay rates obtained by the
      electron paramagnetic resonance spectroscopy (EPRS) and imaging (EPRI). MRRI is a
      dynamic imaging technique employing T1-weighted pulse sequence, which can
      visualise a nitroxyl-induced enhancement of signal intensity by T1-weighted
      contrast. EPR techniques can directly measure the paramagnetic nitroxyl radical.
      Both the squamous cell carcinoma (SCC) tumour-bearing and normal legs of a female
      C3H mouse were scanned by T1-weighted SPGR sequence at 4.7 T with the nitroxyl
      radical, carbamoyl-proxyl (CmP), as the contrast agent. Similarly, the time
      course of CmP in normal muscle and tumour tissues was obtained using a 700-MHz
      EPR spectrometer with a surface coil. The time course imaging of CmP was also
      performed by 300 MHz CW EPR imager. EPRS and EPRI gave slower decay rates of CmP
      compared to the MRRI. Relatively slow decay rate at peripheral region of the
      tumour tissues, which was found in the image obtained by MRRI, may contribute to
      the slower decay rates observed by EPRS and/or the EPRI measurements. To reliably
      determine the tissue redox status from the reduction rates of nitroxyls such as
      CmP, heterogenic structure in the tumour tissue must be considered. The high
      spatial and temporal resolution of T1-weighted MRI and the T1-enhancing
      capabilities of nitroxyls support the use of this method to map tissue redox
      status which can be a useful biomarker to guide appropriate treatments based on
      the tumour microenvironment.

PMID- 29320889
TI  - The cardiovascular effect of incretin-based therapies among type 2 diabetes: a
      systematic review and network meta-analysis.
AB  - OBJECTIVE: To evaluate the comparative cardiovascular safety of incretin-based
      therapies in patients with type 2 diabetes mellitus (T2DM). METHODS: Medline,
      Embase, the Cochrane Library and www.clinicaltrials.gov were searched for
      randomized controlled trials (RCTs) with duration>=12 weeks. Network meta
      analysis was performed, followed by subgroup analysis and meta-regression. The
      Grading of Recommendations Assessment, Development and Evaluation system was used
      to assess the quality of evidence. The outcome of interest was a composite of
      cardiovascular death, myocardial infarction, stroke and heart failure. Odds ratio
      (OR) with 95% confidence interval (CI) was calculated as the measure of effect
      size. RESULTS: 281 RCTs (76.9% double-blinded) with 180,000 patients were
      included, comparing incretin-based therapies with other six classes of anti
      diabetic drugs or placebo. A statistically significant reduction in the risk of
      cardiovascular events was found in favour of GLP-1RAs when compared with placebo
      (OR 0.89, 95%CI: 0.80-0.99) and sulfonylurea (OR 0.76, 95%CI: 0.59-0.99), whereas
      DPP-4 inhibitors showed a neutral effect compared with placebo (OR 0.92, 95%CI:
      0.83-1.01). CONCLUSIONS: Incretin-based therapies show similar cardiovascular
      risk in comparison with metformin, insulin, thiazolidinediones, alpha-glucosidase
      inhibitor and sodium-glucose co-transporter 2. GLP-1RA could decrease the risk
      compared with sulfonylurea or placebo, while DPP-4I appears to have neutral
      effect on cardiovascular risk.

PMID- 29320891
TI  - The political economy of the assessment of value of new health technologies.
AB  - Health technology assessment provides a common framework for evaluating the costs
      and benefits of new health technologies to inform decisions on the public funding
      of new pharmaceuticals and other health technologies. In Australia and England,
      empirical analyses of the opportunity costs of government spending on new health
      technologies suggest more quality adjusted life years are being forgone than are
      being gained by a non-trivial proportion of funded health technologies. This
      essay considers the relevance of available empirical estimates of opportunity
      costs and explores the relationship between the public funding of health
      technologies and broader political and economic factors. We conclude that the
      benefits of a general reduction in the prices paid by governments for new
      technologies outweigh the costs, but evidence of informed public acceptance of
      reduced access to new health technologies may be required to shift the current
      approach to assessing the value of new health technologies.

PMID- 29320890
TI  - Chimeric Antigen Receptors in Different Cell Types: New Vehicles Join the Race.
AB  - Adoptive cellular therapy has evolved into a powerful force in the battle against
      cancer, holding promise for curative responses in patients with advanced and
      refractory tumors. Autologous T cells, reprogrammed to target malignant cells via
      the expression of a chimeric antigen receptor (CAR) represent the frontrunner in
      this approach. Tremendous clinical regressions have been achieved using CAR-T
      cells against a variety of cancers both in numerous preclinical studies and in
      several clinical trials, most notably against acute lymphoblastic leukemia, and
      resulted in a very recent United States Food and Drug Administration approval of
      the first CAR-T-cell therapy. In most studies CARs are transferred to
      conventional alphabetaT cells. Nevertheless, transferring a CAR into different
      cell types, such as gammadeltaT cells, natural killer cells, natural killer T
      cells, and myeloid cells has yet received relatively little attention, although
      these cell types possess unique features that may aid in surmounting some of the
      hurdles CAR-T-cell therapy currently faces. This review focuses on CAR therapy
      using effectors beyond conventional alphabetaT cells and discusses those
      strategies against the backdrop of developing a safe, powerful, and durable
      cancer therapy.

PMID- 29320892
TI  - The effect of the global financial crisis on preventable hospitalizations among
      the homeless in New York State.
AB  - Objective Periods of economic instability may increase preventable
      hospitalizations because of increased barriers to accessing primary care. For
      underserved populations such as the homeless, these barriers may be more
      pronounced due to limited resources in the health care safety net. This study
      examined the impact of the global financial crisis of 2007-2008 on access to care
      for the homeless in New York State. Methods Hospitalizations for ambulatory care
      sensitive conditions (ACSCs) were used as a proxy measure for primary care
      access. Admissions for ACSCs were identified in the New York State Inpatient
      Database from 2006 to 2012. Hospitalization rates for ACSCs were calculated for
      the homeless and nonhomeless. Multivariable linear regression was used to
      investigate the impact of the financial crisis on hospitalization rates for
      ACSCs. Results The findings indicate that during the financial crisis, homeless
      adults had significantly higher preventable hospitalizations than nonhomeless
      adults, and the uninsured homeless had significantly higher preventable
      hospitalizations when compared to other homeless subgroups. After the financial
      crisis, preventable hospitalizations for the homeless stabilized but remained at
      higher rates than those for the nonhomeless. Conclusions These findings are
      important to developing health policies designed to provide effective care for
      underserved population such as the homeless.

PMID- 29320893
TI  - Current Status of Nonviral Vectors for Gene Therapy in China.
AB  - With the growing interest in application of nonviral vectors for drug delivery,
      diagnosis, and imaging, progress has been made in the field of nonviral vector
      gene therapy in China. Nanobiotechnology studies are important to the development
      plan for China's research priorities in the 21st century; the National 973 Plan
      and "Strategic Priority Research Program" classify nanobiotechnology as a special
      project and give priority to supporting its development. From 2000 to 2017, many
      articles on nonviral vector gene therapy were published, and cancer gene therapy
      is one of the most active and important gene therapy research fields. Although
      the use of nonviral vectors for gene therapy faces enormous problems, Chinese
      scientists have also begun to realize both the challenges and opportunities that
      lie ahead. However, a nonviral gene therapy drug has yet to be approved for sale.
      Therefore, more work is needed in this field. The present review examines the
      progress and challenges of nonviral gene therapy in China. Efforts to optimize
      nonviral vectors with structural modifications and gene delivery systems are
      described, and clinical translation challenges are highlighted.

PMID- 29320894
TI  - Biomarkers of tumour redox status in response to modulations of glutathione and
      thioredoxin antioxidant pathways.
AB  - The ability of certain cancer cells to maintain a highly reduced intracellular
      environment is correlated with aggressiveness and drug resistance. Since the
      glutathione (GSH) and thioredoxin (TRX) systems cooperate to a tight regulation
      of ROS in cell physiology, and to a stimulation of tumour initiation and
      progression, modulation of the GSH and TRX pathways are emerging as new potential
      targets in cancer. In vivo methods to assess changes in tumour redox status are
      critically needed to assess the relevance of redox-targeted agents. The current
      study assesses in vitro and in vivo biomarkers of tumour redox status in response
      to treatments targeting the GSH and TRX pathways, by comparing cytosolic and
      mitochondrial redox nitroxide electron paramagnetic resonance (EPR) probes, and
      cross-validation with redox dynamic fluorescent measurement. For that purpose,
      the effect of the GSH modulator buthionine sulfoximine (BSO) and of the TRX
      reductase inhibitor auranofin were measured in vitro using both cytosolic and
      mitochondrial EPR and roGFP probes in breast and cervical cancer cells. In vivo,
      mice bearing breast or cervical cancer xenografts were treated with the GSH or
      TRX modulators and monitored using the mito-TEMPO spin probe. Our data highlight
      the importance of using mitochondria-targeted spin probes to assess changes in
      tumour redox status induced by redox modulators. Further in vivo validation of
      the mito-tempo spin probe with alternative in vivo methods should be considered,
      yet the spin probe used in vivo in xenografts demonstrated sensitivity to the
      redox status modulators.

PMID- 29320895
TI  - Effects of telephone support on exercise capacity and quality of life in patients
      with chronic obstructive pulmonary disease: a meta-analysis.
AB  - The aim of this meta-analysis was to evaluate the effects of disease education or
      pulmonary rehabilitation programs assisted with telephone support on physical
      capacity and quality of life (QOL) in chronic obstructive pulmonary disease
      (COPD) patients. A systematic search of PubMed, Embase, Web of Science and The
      Cochrane Library was conducted until May 2017. Randomized controlled trials
      (RCTs) examining the effects of telephone-assisted intervention versus a control
      group on exercise tolerance and QOL in patients with COPD were included. Two
      independent authors assessed the methodological quality of the trials using the
      Cochrane risk of bias tool. A meta-analysis was conducted with the Revman5.3 to
      quantify the effects of telephone-assisted interventions on walking capacity and
      QOL. In total, 10 studies involving 1037 participants were included. Due to the
      effect of telephone-assisted interventions, statistically significant results
      were found on Saint-George's Respiratory Questionnaire (SGRQ) symptom scores
      [standard mean difference (SMD) -.18, 95% confidence interval (CI) -.33, -.03, p
      value .02)], SGRQ impact scores [SMD -.35, 95% CI -.60, -.10, p-value .006)],
      SGRQ activity scores [SMD -.30, 95% CI -.45, -.15, p-value < .0001)], SGRQ total
      score [SMD -.36, 95% CI -.51, -.21, p-value < .00001)]. The effects on 6-min walk
      test (6MWT) and all Chronic Respiratory Questionnaire (CRQ) subscales were not
      significant (p > .05) based on the insufficient evidence. In conclusion, the role
      of telephone-assisted interventions in the management of COPD remains equivocal.
      Some encouraging results were seen with regard to SGRQ symptom, SGRQ impact, SGRQ
      activity and SGRQ total score. We believe that more methodologically rigorous
      large-scale randomized controlled trials are necessary to answer this study
      question.

PMID- 29320896
TI  - Mortality rate and oral health - a cohort study over 44 years in the county of
      Stockholm.
AB  - OBJECTIVE: To study the association between oral health and all-cause mortality
      rate over 44 years. In addition, the specific relations between oral health and
      death caused by cardiovascular disease (CVD), cancer or other reasons were
      investigated. MATERIALS AND METHODS: An epidemiological investigation studying
      the oral health of the population consisting of 1393 randomly selected subjects
      was performed in the County of Stockholm. The individuals were invited to a
      clinical examination, an interview and a radiographic examination. The incidence
      of mortality during the years 1970-2014 as well as the causes of death according
      to the death certificate were registered in 2015. Cox regression survival
      analysis was used for investigating the effect of several variables upon the time
      to the outcome of death. RESULTS: Forty-six percent of the subjects were still
      alive at the end of the year 2014. Cancers caused 27% of the deaths, while 22%
      died due to CVD. The mortality risk was positively and significantly correlated
      to oral health when compensated for age, sex, smoking and social status. In
      addition, the mortality risk caused by CVD, cancer or other reasons was
      significantly increased for those with poor oral health. CONCLUSIONS: Oral health
      was found to be a risk indicator of death caused by CVD and cancer as well as for
      all-cause mortality. Thus, the associations are unspecific. Harmful lifestyle
      factors impact dental health behavior as well as mortality risk. This might
      contribute to the association between oral health and mortality risk.

PMID- 29320897
TI  - Changes in resting motor threshold of the tongue with normal aging and stroke.
AB  - AIM OF STUDY: To examine the resting motor threshold of the tongue in healthy
      adults and stroke survivors. METHODS: Thirty-five healthy adults were classified
      into three groups: Group 1 (19-38 years; n = 11), Group 2 (50-64 years; n = 12)
      and Group 3 (66-78 years; n = 12). Six chronic stroke survivors (mean age =59
      years, SD = 9.1 years) were recruited (Group 4). The resting motor thresholds
      (RMTs) of the tongue were measured and compared (i) among the four groups and
      (ii) between stroke survivors and age-matched healthy adults. RESULTS: Group 3
      showed significantly higher RMTs than Group 1 (p = .001) and 2 (p = 0.007). Group
      4 showed significantly higher RMTs than Group 1 (p = .003) and 2 (p = .001). The
      RMTs of Group 3 and 4 were not significantly different (p = .385). The RMT was
      positively correlated with age (r = 0.534; p = .001). Group 4 showed
      significantly higher RMTs than the age-matched controls (U = 2.5, p = .009, r =
      0.77). CONCLUSIONS: The resting motor threshold of the tongue is significantly
      increased in adults aged above 65 and in stroke survivors when compared with
      healthy adults. The findings suggested that the cortical excitability of the
      tongue deteriorates in the elderly and the stroke population.

PMID- 29320898
TI  - Did I Miss It? Discovering Hidden Coexisting Hematological Neoplasms: A Single
      Institutional Review of 100 Collision Tumors.
AB  - A collision tumor is defined as two histologically distinct tumor types
      identified at the same anatomic site. Hematolymphoid proliferative disorders
      (HLPDs), which coincide with non-hematological neoplasms, can mimic an immune
      response and can easily be overlooked as an immune reaction to a solid organ
      neoplasm, especially when low grade. In order to avoid a delay in the diagnosis
      of a HLPD during the workup for a non-hematological neoplasm, we identified a
      cohort of 100 cases with a HLPD diagnosis during the initial workup and treatment
      of a non-hematological neoplasm, or vice versa. Among the 100 collision tumors,
      the most common non-hematological neoplasms associated with a HLPD were from the
      colon (17%), breast (15%), and prostate (12%). The most commonly identified HLPDs
      were chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL; 18%),
      diffuse large B-cell lymphoma (17%), follicular lymphoma (14%), marginal zone
      lymphoma (10%), acute myeloid leukemia (8%), and classical Hodgkin lymphoma (5%).
      Interestingly, in this cohort 5% of the low-grade HLPDs, all of them CLL/SLL,
      were missed at initial sign-out and subsequently required an addendum report. The
      other 95% of cases were reviewed or signed out by a hematopathologist before the
      report was finalized for the non-hematological neoplasm. In summary, high-grade
      hematological malignancies are less likely to be missed; however, low-grade
      coexisting HLPDs can be overlooked as a reactive immune response to a solid organ
      neoplasm. Therefore, it is important to keep in mind the existence of collision
      low-grade HLPDs before assuming the lymphoid infiltrates as an immunological
      response.

PMID- 29320899
TI  - In vitro analysis of itraconazole cis-diastereoisomers inhibition of nine
      cytochrome P450 enzymes: stereoselective inhibition of CYP3A.
AB  - 1. Itraconazole (ITZ), an antifungal azole derivate is a chiral drug that
      consists of four cis-diastereoisomers ((+)-2R,4S,2'R-ITZ-A; (+)-2R,4S,2'S-ITZ-B;
      (-)-2S,4R,2'S-ITZ-C and (-)-2S,4R,2'R-ITZ-D) which may differ in their
      pharmacokinetics and pharmacodynamics. 2. As ITZ is known as a CYP3A4 inhibitor
      causing severe drug-drug interaction, the inhibitory potencies of its individual
      optical isomers towards nine drug-metabolising cytochrome P450 (including CYP3A,
      CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP2E1), were
      investigated. 3. All ITZ diastereoisomers dose-dependently inhibited CYP3A
      activity in both used assays, midazolam and testosterone hydroxylation. The Ki
      values were assessed: for testosterone ITZ-A/0.085 uM; ITZ-B/0.91 uM, ITZ-C/0.20
      uM and ITZ-D/0.022 uM; for midazolam ITZ-A/0.44 uM; ITZ-B/0.48 uM, ITZ-C/1.56 uM
      and ITZ-D/3.48 uM. The enzyme activity of CYP2C19 was moderately inhibited (IC50
      30-53 uM), but in this case without large differences between the individual
      optical isomers. 4. The significant differences between diastereoisomers were
      presented. Antifungal potency of ITZ stereoisomers also differs so the potential
      enantiopure preparations of ITZ was not of interest.

PMID- 29320901
TI  - If we keep doing what we're doing we'll keep getting what we're getting: A need
      to rethink "academic" medicine.
AB  - PURPOSE: For generations there have been warnings of the need to reform medical
      education at all levels. Today the voices pushing reform are louder, the need is
      greater, and there is an urgency not seen before. Approaches that have worked in
      the past to train physicians are no longer as relevant today as demographics,
      disease patterns, human resources, practice behaviors, technology, and attention
      to costs demand new collaborative approaches to clinical practice. To prepare for
      this practice tomorrow's doctors will need a different type of educational model,
      a different type of learning, in different environments, often taught by
      different faculty. This paper provides one innovative approach to redefine
      "academic medicine". METHODS: After reviewing current trends in medical
      education, this paper describes one approach being taken by a large nonprofit
      American health care system to move medical education and discovery (research)
      out of traditional academic universities and placing it within a health care
      delivery system. CONCLUSIONS: The creation of a learning laboratory in a high
      functioning health care delivery system allows for leveraging the successes in
      quality health care delivery to transform medical education with a focus on
      prevention, improving health care quality, reducing disparities in health, and
      promoting practical evidence-based clinical and outcomes focused research.

PMID- 29320900
TI  - Societal costs of multiple sclerosis in Ireland.
AB  - AIMS: This paper evaluates the impact of multiple sclerosis (MS) in Ireland, and
      estimates the associated direct, indirect, and intangible costs to society based
      on a large nationally representative sample. MATERIALS AND METHODS: A
      questionnaire was developed to capture the demographics, disease characteristics,
      healthcare use, informal care, employment, and wellbeing. Referencing
      international studies, standardized survey instruments were included (e.g. CSRI,
      MFIS-5, EQ-5D) or adapted (EDSS) for inclusion in an online survey platform.
      Recruitment was directed at people with MS via the MS Society mailing list and
      social media platforms, as well as in traditional media. The economic costing was
      primarily conducted using a 'bottom-up' methodology, and national estimates were
      achieved using 'prevalence-based' extrapolation. RESULTS: A total of 594 people
      completed the survey in full. The sample had geographic, disease, and demographic
      characteristics indicating good representativeness. At an individual level,
      average societal cost was estimated at ?47,683; the average annual costs for
      those with mild, moderate, and severe MS were calculated as ?34,942, ?57,857, and
      ?100,554, respectively. For a total Irish MS population of 9,000, the total
      societal costs of MS amounted to ?429m. Direct costs accounted for just 30% of
      the total societal costs, indirect costs amounted to 50% of the total, and
      intangible or QoL costs represented 20%. The societal cost associated with a
      relapse in the sample is estimated as ?2,438. LIMITATIONS AND CONCLUSIONS: The
      findings highlight that up to 70% of the total costs associated with MS are not
      routinely counted. These "hidden" costs are higher in Ireland than the rest of
      Europe, due in part to significantly lower levels of workforce participation, a
      higher likelihood of permanent workforce withdrawal, and higher levels of
      informal care needs. The relationship between disease progression and costs
      emphasize the societal importance of managing and slowing the progression of the
      illness.

PMID- 29320902
TI  - CD33 splicing SNP regulates expression levels of CD33 in normal regenerating
      monocytes in AML patients.

PMID- 29320904
TI  - Free first dorsal metatarsal artery perforator flap for multiple finger defects
      reconstruction: a case report.

PMID- 29320903
TI  - Air Pollution and Human Sperm Sex Ratio.
AB  - The present study was designed to address the hypothesis that exposure to
      specific air pollutants may impact human sperm Y:X chromosome ratio. The study
      population consisted of 195 men who were attending an infertility clinic for
      diagnostic purposes and who had normal semen concentration of 15-300 mln/ml (WHO,
      2010). Participants represented a subset of men in a multicenter parent study
      conducted in Poland to evaluate environmental factors and male fertility.
      Participants were interviewed and provided a semen sample. The Y:X ratio was
      assessed by fluorescent in situ hybridization (FISH). Air quality data were
      obtained from the AirBase database. In multivariate analysis the significant
      reduction was observed in the proportion of Y/X chromosome bearing sperm and
      exposure to particulate matter >10 MUm in aerodynamic diameter PM10 ( p = .009)
      and particulate matter <10 MUm in aerodynamic diameter PM2.5 ( p = .023). The
      observed effects of a lower Y:X sperm chromosome ratio among men exposed to air
      pollution support the evidence that the trend of declining sex ratio in several
      societies over past decades has been due to exposure to air pollution; however
      due to limited data on this issue, the obtained results should be confirmed in
      longitudinal studies.

PMID- 29320905
TI  - Mid- to long-term outcomes of collateral ligament repairs of 18
      metacarpophalangeal joints with bone suture anchors.

PMID- 29320906
TI  - A bifid reversed palmaris longus muscle causing median nerve compression in a
      child.

PMID- 29320907
TI  - A single injection metacarpal block of the second digital ray: an easy, efficient
      and patient friendly technique.

PMID- 29320908
TI  - Psychiatric diagnoses and their influencing factors in patients complaining of
      sleep problems: A study of a psychiatric consultation-liaison service.
AB  - Objective This study aimed to identify misdiagnosed or undiagnosed psychiatric
      disorders and the factors associated with these disorders in patients with sleep
      problems who are referred to a consultation-liaison service. Method Records of
      all inpatients receiving a consultation from the Psychiatry Department between
      January and December 2016 were retrospectively reviewed. Psychiatric diagnoses
      were analyzed using descriptive statistics, and the factors associated with the
      risk of these disorders in patients with sleep problems were determined by
      multiple logistic regression analysis. Results Of the 331 referral patients whose
      referral reason was simply having trouble in sleeping, only 97 patients were
      diagnosed with primary sleep disorder after consultation. The recognition rate of
      psychiatric disorders in inpatients with sleep problems among nonpsychiatric
      physicians was 29.3%. Anxiety (107, 45.7%) was the most common psychiatric
      diagnosis in patients with sleep problems followed by organic mental disorder
      (83, 35.5%), depression (37, 15.8%), and other mental disorders (8, 3.4%).
      Multiple logistic regression analysis revealed that a course >1 month (OR =
      3.656, 95% CI = 2.171-6.156, p = 0.000) and sleep-wake rhythm disturbances (OR =
      25.008, 95% CI = 5.826-107.341, p = 0.000) were associated with increased risks
      of psychiatric disorders. Conclusions The study showed that recognition rate of
      psychiatric disorders in inpatients with sleep problems was very low. A course >1
      month and sleep-wake rhythm disturbances were associated with increased risks of
      disorders and could be used as indicators by nonpsychiatric physicians to improve
      diagnoses.

PMID- 29320909
TI  - Vascularization of Lando(r) dermal scaffold in an acute full-thickness skin
      defect porcine model.
AB  - The Lando(r) dermal scaffold is a newly developed, tissue-engineered dermal
      scaffold material. This study sought to observe its vascularization in an acute
      full-thickness skin-defect porcine model. There were eight Tibetan pigs in this
      research. Six 5 * 5 cm full-thickness skin-defect wounds were prepared on the
      dorsal area of each pig, which were divided into two groups. The experimental
      group wounds were covered by Lando(r) dermal scaffolds, while the other received
      Vaseline gauzes as blank control. At day 3, 7, 14 and 21 after injury, the
      general condition of wounds was observed, and wound specimens were obtained for
      HE staining, Masson staining and the expression of CD31, alpha-SMA and VEGF,
      which were examined by immunohistochemistry. The results showed the wounds in the
      experimental group (Lando) were drier with a lower incidence of infection, and
      the granulation tissues grew better and smoother than the control group. In the
      experimental group, the hyperemia, edema and inflammatory reactions were milder,
      the fibroblasts ingrew earlier, the capillaries grew mostly parallel to the wound
      surface which resembled normal skin, and the collagen fibers were thicker with
      more regular arrangement than in the control group. The CD31 + microvessel count,
      alpha-SMA + microvessel count and VEGF expression of the experimental group were
      significantly higher than the control group at day 7 and 14 after injury (p <
      .05). In conclusion, the Lando(r) dermal scaffold showed good vascularization at
      day 14 post grafting in an acute full-thickness skin-defect porcine model, which
      may be associated with increased expression of VEGF.

PMID- 29320910
TI  - Predicting and explaining inflammation in Crohn's disease patients using
      predictive analytics methods and electronic medical record data.
AB  - Crohn's disease is among the chronic inflammatory bowel diseases that impact the
      gastrointestinal tract. Understanding and predicting the severity of inflammation
      in real-time settings is critical to disease management. Extant literature has
      primarily focused on studies that are conducted in clinical trial settings to
      investigate the impact of a drug treatment on the remission status of the
      disease. This research proposes an analytics methodology where three different
      types of prediction models are developed to predict and to explain the severity
      of inflammation in patients diagnosed with Crohn's disease. The results show that
      machine-learning-based analytic methods such as gradient boosting machines can
      predict the inflammation severity with a very high accuracy (area under the curve
      = 92.82%), followed by regularized regression and logistic regression. According
      to the findings, a combination of baseline laboratory parameters, patient
      demographic characteristics, and disease location are among the strongest
      predictors of inflammation severity in Crohn's disease patients.

PMID- 29320911
TI  - Turning challenges into design principles: Telemonitoring systems for patients
      with multiple chronic conditions.
AB  - People with multiple chronic conditions often struggle with managing their
      health. The purpose of this research was to identify specific challenges of
      patients with multiple chronic conditions and to use the findings to form design
      principles for a telemonitoring system tailored for these patients. Semi
      structured interviews with 15 patients with multiple chronic conditions and 10
      clinicians were conducted to gain an understanding of their needs and preferences
      for a smartphone-based telemonitoring system. The interviews were analyzed using
      a conventional content analysis technique, resulting in six themes. Design
      principles developed from the themes included that the system must be modular to
      accommodate various combinations of conditions, reinforce a routine, consolidate
      record keeping, as well as provide actionable feedback to the patients. Designing
      an application for multiple chronic conditions is complex due to variability in
      patient conditions, and therefore, design principles developed in this study can
      help with future innovations aimed to help manage this population.

PMID- 29320912
TI  - Fostering Transformation by Hearing Voices: Evaluating a 6-Second, Low-Fidelity
      Simulation.
AB  - BACKGROUND: The stigma of psychosis, with the accompanying symptoms of auditory
      and visual hallucinations, can affect a nurse's ability to provide safe,
      effective care. Increasing knowledge of the patient's perspective during auditory
      hallucinations can increase the nurse's ability to be empathetic and engage in a
      therapeutic alliance. OBJECTIVE: To evaluate the efficacy of a six-second
      auditory hallucination simulation to increase empathy in preclinical
      undergraduate nursing students. DESIGN: This descriptive, content analysis,
      qualitative study evaluated narratives written by students in a pre-licensure
      baccalaureate nursing student population, assessing empathy, insight, knowledge,
      and therapeutic communication. Students experienced the 6-second auditory
      hallucination simulation as part of preclinical instruction, and then they wrote
      a self-reflection. RESULTS: More than 200 self-reflections were collected, with a
      randomized final sample of 82 narratives evaluated. CONCLUSION: Self-reflections
      indicated that the experience of the 6-second hearing voices simulation increased
      efficacy, insight, knowledge, and intention to use therapeutic communication.

PMID- 29320913
TI  - A phase 2 study of rituximab, cyclophosphamide, bortezomib and dexamethasone (R
      CyBorD) in relapsed low grade and mantle cell lymphoma.
AB  - In this phase 2 trial, we sought to evaluate the efficacy and safety of
      rituximab, cyclophosphamide, bortezomib, and dexamethasone (R-CyBorD) in patients
      with low-grade NHL. The regimen included rituximab on day 1 with weekly
      cyclophosphamide, dexamethasone, and bortezomib 1.3 mg/m2 IV in a 28-day cycle.
      Twenty one patients were enrolled on the study. Median age was 69 years (range 51
      80) and 17 (81%) patients had two or more prior treatments. Histologies included
      FL (n = 8), MCL (n = 8), and LPL/WM (n = 5). Hematologic toxicity and peripheral
      sensory neuropathy were the most common adverse events. With a median follow-up
      of 38.1 months, ORR was 13/21 (62%), with 4 (19%) CR. The ORR was 7/8 (88%) in FL
      and was 4/5 (80%) in LPL/WM. Median PFS and OS were 11.6 months and 54.8 months,
      respectively. R-CyBorD is an effective regimen in relapsed FL and LPL/WM patients
      with an acceptable safety profile.

PMID- 29320914
TI  - Early treatment of intrapericardial teratoma: a case presentation and systematic
      literature review.
AB  - OBJECTIVE: To present a case of an early treatment of cardiac intraperitoneal
      teratoma (IPT) in a newborn and its associated systematic literature review.
      METHODS: We presented a case of a newborn with IPT but without hydrops and having
      a good perinatal outcome after cardiac surgery. Using the PubMed database, we
      conducted a systematic literature review of articles regarding cases with cardiac
      IPT diagnosed and treated in the neonatal period and published in English from
      2004 onward. We excluded cases that involved fetal death or interrupted gestation
      events. RESULTS: In total, 38 cases of IPT from 31 articles were included. The
      mean +/- standard deviation of the gestational age at diagnosis and delivery were
      27.9 +/- 5.7 and 33.0 +/- 3.5 weeks, respectively, and that of birth weight was
      2373 +/- 834.5 g. The majority of fetuses (42.1%) were males. Pericardial
      effusion was the most common symptom (60.5%) followed by hydrops (42.1%) and
      respiratory distress (42.1%). Intrauterine procedure was not performed in 63.1%
      of cases, and 71.0% of newborns were alive. CONCLUSIONS: IPT in newborns is
      usually associated with a good prognosis without the need for intrauterine
      procedures. Cases with IPT-related death are associated with hemodynamic
      impairment in fetuses with hydrops.

PMID- 29320916
TI  - The reliability of the Montreal Cognitive Assessment using telehealth in a rural
      setting with veterans.
AB  - Background Telehealth neuropsychological services can increase the availability
      of specialised care for individuals in rural areas where barriers to these
      services are faced. As this practice becomes more commonplace, the reliability
      and validity of neuropsychological assessment administered by telehealth
      continues to be established. The Montreal Cognitive Assessment, a screener for
      general neurocognitive dysfunction, may be particularly useful since this measure
      can be given by telehealth with minimal adaptation. Methods Veterans from a rural
      area of the country who were referred to an outpatient neuropsychology clinic
      were administered the Montreal Cognitive Assessment either in-person or by
      telehealth by a clinician. A second clinician observed the administration in
      person or by telehealth and independently scored the each participant's
      performance. The inter-rater reliabilities across conditions were compared to
      assess for differences between in-person and telehealth consultations. Results
      The inter-rater reliability of the Montreal Cognitive Assessment across the three
      conditions of interest was acceptably high and values ranged from r = 0.88 to r =
      0.98. Reliability correlations were compared and no significant differences among
      the conditions were observed ( p's > 0.10). Beyond reliability, univariate
      comparison of the absolute mean differences of clinician scores showed no
      significant differences among the actual raw scores of the three conditions
      tested, indicating good accuracy ( p = 0.56). Conclusions The inter-rater
      reliabilities of Montreal Cognitive Assessment scores across conditions were all
      acceptably high, and administration of the Montreal Cognitive Assessment using
      telehealth technology did not significantly alter the total scores. Overall, the
      lack of significant differences suggests that administering the Montreal
      Cognitive Assessment by telehealth is reliable, accurate and well received by
      participants.

PMID- 29320915
TI  - Healthcare utilization and costs associated with treatment for opioid dependence.
AB  - OBJECTIVE: Opioid use disorder (OUD) can be managed with medication assisted
      therapy (MAT) (methadone [MET], buprenorphine [BUP], or extended-release
      naltrexone [XR-NTX]) or counseling alone (non-pharmacological therapy [NPT]). The
      objective of this study was to evaluate healthcare resource utilization and costs
      associated with XR-NTX compared with alternative treatments for opioid
      dependence. METHODS: Adults with a diagnosis of opioid dependence who initiated
      treatment with XR-NTX, BUP, MET, or NPT between January 1, 2011 and December 31,
      2014 were identified in the Truven Health MarketScan Commercial administrative
      claims database. Healthcare resource utilization, costs (inpatient [IP],
      emergency department [ED], outpatient [OP], and pharmacy) and adherence were
      evaluated for each cohort during 12-month baseline and follow-up periods.
      RESULTS: A total of 29,235 patients were included in the analysis; 1,041, 20,566,
      745, and 6,883 received XR-NTX, BUP, MET, and NPT, respectively. Patients in the
      XR-NTX cohort were significantly younger and had more comorbidities compared with
      the other cohorts. Patients in the XR-NTX group had the largest percentage
      decrease in IP and ED utilization and costs from baseline to follow-up. OP and
      pharmacy costs increased significantly from baseline to follow-up for all
      cohorts. Overall, there was no significant change in total healthcare costs for
      the XR-NTX group, whereas the costs increased significantly for other groups (BUP
      = +43%, MET = +47.7%, NPT = +38.8%). CONCLUSIONS: Healthcare resource utilization
      and costs increased from baseline to follow-up in BUP, MET, and NPT patients,
      whereas patients receiving XR-NTX experienced no such increase. This analysis
      suggests there may be economic value in the use of XR-NTX for OUD.

PMID- 29320917
TI  - Hypoesthesia in generalised anxiety disorder and major depression disorder.
AB  - OBJECTIVE: The determination of soft signs can be a conducive practice to
      understand the differential etiology between depression and anxiety. This study
      aims at examining malleolar hypoesthesia role in distinguishing between patients
      with generalised anxiety disorder (GAD) and major depression disorder (MDD).
      METHODS: This study examines the presence of malleolar hypoesthesia in patients
      with GAD (n = 47) compared to patients with MDD (n = 48) and healthy individuals
      (controls; n = 99). The Wartenberg wheel, a medical device for neurological use,
      was employed to determine the presence of hypoesthesia on both sides of the
      ankles. RESULTS: The data revealed: i) MDD patients showed higher hypoesthesia
      than GAD patients (p = .008), ii) participants with hypoesthesia had higher
      anxiety and depression scores than participants without hypoesthesia (all p <
      .001) and iii) logistic regression model indicated that hypoesthesia can be a
      predictor of MDD relative to GAD diagnosis (Odds Ratio: 17.43 (1.40-217.09; p =
      .026)). CONCLUSIONS: Malleolar hypoesthesia was higher in MDD than GAD. The
      detection of hypoesthesia may help to investigate the differential etiology
      between MDD and GAD diagnosis.

PMID- 29320918
TI  - The rs1256044 polymorphism in the ESR2 gene and the risk for osteoporosis in
      Polish postmenopausal women.
AB  - Population association studies have demonstrated a strong association between
      ESR2 SNPs and BMD, indicating that ESR2 may influence attainment of bone mass.
      The aim of the study was to investigate the ESR2 gene, located on chromosome 14q
      linked with BMD, which demonstrates a correlation with changes in bone mass in
      healthy Caucasian women. The study included 675 unrelated Polish postmenopausal
      women, including 109 with osteopenia, 333 with osteoporosis and 233 healthy
      women. The women were classified into the following groups: osteopenia,
      osteoporosis and normal T-score. Analysis of genotype frequency for the ESR2
      rs1256044 polymorphism revealed no statistically significant differences. No
      statistically significant differences were noted for the allele frequency.
      However, it is noticeable that the CT genotype occurred more often in women with
      osteopenia (50.4%, OR = 1.14) and osteoporosis (54.7%, OR = 1.33) than controls
      (47.7%). There were statistically significant differences between the clinical
      parameters and distribution of genotypes in patients with osteopenia but not
      osteoporosis. ESR2 polymorphisms demonstrate minimal influence on BMD changes in
      women. Identification of various genes with little impact on BMD, such as ESR2,
      might help design a screening panel for osteoporosis risk assessment in healthy
      subjects.

PMID- 29320919
TI  - Does school physical education really contribute to accelerometer-measured daily
      physical activity and non sedentary behaviour in high school students?
AB  - Physical education has been highlighted as an important environment for physical
      activity promotion, however, to our knowledge there are no previous studies
      examining the contribution of physical education to daily accelerometer-measured
      physical activity and non sedentary behaviour. The purpose was to compare the
      accelerometer-measured physical activity and sedentary behaviour between physical
      education, non-physical education and weekend days in adolescents. Of the 394
      students from a Spanish high school that were invited to participate, 158
      students (83 boys and 75 girls) aged 13-16 years were analyzed (wear time >= 600
      min). Participants' physical activity and sedentary behaviour were objectively
      measured by GT3X+ accelerometers during physical education (one session), non
      physical education and weekend days. Results indicated that overall adolescents
      had statistically significant greater physical activity levels and lower values
      of sedentary behaviour on physical education days than on non-physical education
      and weekend days (e.g., moderate-to-vigorous physical activity = 71, 54 and 57
      min; sedentary = 710, 740 and 723 min) (p < 0.05). Physical education contributes
      significantly to reducing students' daily physical inactivity and sedentary
      behaviour. Increasing the number of physical education classes seems to be an
      effective strategy to reduce the high current prevalence of physical inactivity
      and sedentary behaviour in adolescence.

PMID- 29320920
TI  - Patency of uterine wall in pregnancies following assisted and spontaneous
      conception with antecedent laparoscopic and abdominal myomectomies - a difficult
      case and systematic review.
AB  - A case of uterine rupture at 24 weeks in a pregnancy succeeding myomectomy and
      triple embryo transfer is described and literature is reviewed systematically to
      evaluate the importance of uterine rupture in pregnancies after myomectomy in
      general and some important sub-populations. Systematic search identified 179
      papers and following a strategical selection process 45 studies were analyzed in
      detail, including 6 cohort and 19 observational studies, 3 case series and 17
      case reports. Comparison of risk of uterine rupture after abdominal and
      laparoscopic myomectomy is made. In pregnancies after IVF number of embryos
      transferred are determined. Optimal contraceptive intervals and surgical
      techniques are discussed. The consequences of these observations are analyzed and
      conclusions are made which can assist individualizing treatment options and
      improve patient selection.

PMID- 29320921
TI  - Benefits and risks with acellular dermal matrix (ADM) and mesh support in
      immediate breast reconstruction: a systematic review and meta-analysis.
AB  - In modern implant-based immediate breast reconstruction, it has become common to
      use biological acellular dermal and synthetic matrices in combination with a
      tissue expander or an implant. The aim of this systematic review was to examine
      differences in recurrence of cancer, impact on oncological treatment, health
      related quality of life, complications and aesthetic outcome between matrix and
      no matrix in immediate breast reconstruction. Systematic searches, data
      extraction and assessment of methodological quality were performed according to
      predetermined criteria. Fifty-one studies were eligible and included in the
      review. The certainty of evidence for overall complication rate and implant loss
      is low (GRADE ??? ?). The certainty of evidence for delay of adjuvant treatment,
      implant loss, infection, capsular contraction and aesthetic outcome is very low
      (GRADE ?? ? ?). No study reported data on recurrence of cancer or health related
      quality of life. In conclusion, there is a lack of high quality studies that
      compare the use of matrix with no matrix in immediate breast reconstruction.
      Specifically, there are no data on risk of recurrence of cancer, delay of
      adjuvant treatment and Health related quality of life (HRQoL). In addition, there
      is a risk of bias in many studies. It is often unclear what complications have
      been included and how they have been diagnosed, and how and when capsular
      contracture and aesthetic outcome have been evaluated. Controlled trials that
      further analyse the impact of radiotherapy, type of matrix and type of procedure
      (one or two stages) are necessary.

PMID- 29320922
TI  - Co-Emergence of Specialized Endothelial Cells from Embryonic Stem Cells.
AB  - A well-formed and robust vasculature is critical to the health of most organ
      systems in the body. However, the endothelial cells (ECs) forming the vasculature
      can exhibit a number of distinct functional subphenotypes like arterial or venous
      ECs, as well as angiogenic tip and stalk ECs. In this study, we investigate the
      in vitro differentiation of EC subphenotypes from embryonic stem cells (ESCs).
      Using our staged induction methods and chemically defined mediums, highly
      angiogenic EC subpopulations, as well as less proliferative and less migratory EC
      subpopulations, are derived. Furthermore, the EC subphenotypes exhibit distinct
      surface markers, gene expression profiles, and positional affinities during
      sprouting. While both subpopulations contained greater than 80% VE-cad+/CD31+
      cells, the tip/stalk-like EC contained predominantly Flt4+/Dll4+/CXCR4+/Flt-1-
      cells, while the phalanx-like EC was composed of higher numbers of Flt-1+ cells.
      These studies suggest that the tip-specific EC can be derived in vitro from stem
      cells as a distinct and relatively stable EC subphenotype without the benefit of
      its morphological positioning in the sprouting vessel.

PMID- 29320923
TI  - The effect of seated pelvic tilt on posterior edge-loading in total hip
      arthroplasty: A finite element investigation.
AB  - Edge-loading of a ceramic-on-ceramic total hip replacement can lead to
      reproducible squeaking and revision. A patient's functional acetabular cup
      orientation, driven by their pelvic tilt, has been shown to be a significant
      factor in squeaking during hip flexion. The aim of this study was to investigate
      the effect of seated pelvic tilt on the contact mechanics at the ceramic bearing
      surface. A finite element model of a ceramic-on-ceramic total hip replacement was
      created. The cup was orientated at 40 degrees  inclination and 15 degrees 
      anteversion relative to the anterior pelvic plane. The stem was flexed 90 degrees
      to replicate sitting in a chair. The model was loaded using data from in vivo
      measurements taken during a sit-to-stand activity. The pelvis was modelled in
      seven different sagittal positions, ranging from -30 degrees  to 30 degrees  of
      pelvic tilt, where a positive value denotes anterior pelvic tilt. Three different
      head sizes were investigated: 32, 36 and 40 mm. The maximum contact pressure and
      contact patch to rim distance were determined for each of the 21 simulations.
      Edge-loading (contact patch to rim distance < 0 mm) occurred with all head sizes
      when seated pelvic tilt was >=10 degrees  and induced a large increase in contact
      pressure on the liner, with a maximum pressure exceeding 500 MPa. Edge-loading
      initiated at seated pelvic tilts of 7 degrees , 9 degrees  and 5 degrees  for the
      32, 36 and 40 mm heads, respectively. Patients with anterior pelvic tilts in the
      seated position are susceptible to posterior edge-loading. As the position of the
      pelvis when seated is patient specific, cup orientation should be adjusted on an
      individual basis to minimise edge-loading.

PMID- 29320924
TI  - A model to evaluate Pauwels type III femoral neck fractures.
AB  - While many femoral neck fractures can be reliably treated with surgical
      intervention, Pauwels III femoral neck fractures in the young adult population
      continue to be a challenging injury, and there is no consensus on optimal
      treatment. As such, there are past and ongoing biomechanical studies to evaluate
      the fixation provided by different constructs for this inherently unstable
      fracture. While many investigations rely on cadavers to evaluate the
      biomechanical performance of a construct, significant inter-subject variability
      can confound the analysis. Biomechanical femur analogs are being used more
      frequently due to more consistent mechanical properties; however, they have not
      been stringently evaluated for morphology or suitability for instrumentation.
      This study sought to determine the variability among composite femoral analogs as
      well as consistently create a Pauwels III injury and instrument the analogs
      without the need for fluoroscopic guidance. In total, 24 fourth-generation
      composite femoral analogs were evaluated for femoral height, neck-shaft angle,
      anteversion, and cortical thickness. A method was developed to simulate a Pauwels
      III fracture and to prepare three different constructs: an inverted triangle of
      cannulated screws, a sliding hip screw, and a hybrid inverted triangle with
      cannulated screws and a sliding hip screw. Radiographs were utilized to evaluate
      the variation in implant position. All but one of the morphological parameters
      varied by <1%. The tip-to-apex distance for all sliding hip screw hardware was
      18.8 +/- 3.3 mm, and all relevant cannulated screw distances were within 5 mm of
      the adjacent cortex. All screws were parallel, on average, within 1.5 degrees  on
      anterior-posterior and lateral films. Fourth-generation composite femora were
      found to be morphologically consistent, and it is possible to consistently
      instrument the analogs without the use of fluoroscopy. This analog and hardware
      implantation model could serve as a screening model for new fracture repair
      constructs without the need for cadaveric tissues or radiologic technology.

PMID- 29320925
TI  - Self-Perceived and Actual Motor Competence in Young British Children.
AB  - Children's perception of their own motor competence is an important correlate of
      their actual motor competence. The current study is the first to examine this
      association in British children and the first to use both product and process
      measures of actual motor competence. A total of 258 children (139 boys and 119
      girls; aged 4 to 7 years, Mean = 5.6, SD = .96) completed measures of self
      perceived motor competence using the Pictorial Scale for Perceived Movement
      Competence in Young Children. Children were classified as "Low," "Medium," or
      "High" perceived competence based on tertile analysis. Actual motor competence
      was assessed with the Test of Gross Motor Development-2 (a process measure) and a
      composite of 10-m sprint run time, standing long jump distance, and 1-kg seated
      medicine ball throw (collectively, a product measure). Data for process and
      product measures were analyzed using a 2 (sex) * 3 (high, medium, low perceived
      competence) analysis of covariance, with body mass index, calculated from height
      and mass, and age controlled. Boys obtained significantly higher scores than
      girls for both the process ( p = .044) and product ( p = .001) measures of actual
      motor competence. Boys had significantly ( p = .04) higher scores for perceived
      competence compared to girls. Compared to children classified as medium and high
      self-perceived competence, children classified as low self-perceived competence
      had lower process ( p = .001) and product scores (i.e., medium, p = .009 and
      high, p = .0001) of actual motor competence. Age ( p = .0001) and body mass index
      ( p = .0001) were significantly associated with product motor competence.
      Strategies to enhance actual motor competence may benefit children's self
      perceived motor competence.

PMID- 29320926
TI  - Brain perfusion fixation in male pigs using a safer closed system.
AB  - Tissue fixation methods are well established for rodents, but not for large
      animals. We present a simple technique for in situ brain perfusion fixation in a
      male porcine model, using cervical vessels for inflow and outflow and achieving a
      closed system. Thirty-four pigs, aged 4.7 +/- 0.6 months and weighing 60.7 +/-
      10.9 kg, were anaesthetised and mechanically ventilated. The ipsilateral common
      carotid artery and external jugular vein were dissected and constituted the
      inflow and outflow access, respectively. The brains were perfused and fixed in
      situ with heparinised saline followed by buffered formaldehyde. Then, specimens
      (brain, cerebellum and brainstem) were extracted and processed for histology.
      Fixative fluid leakage was avoided, achieving a closed system. This technique
      minimises the exposure to toxic chemicals such as formaldehyde and associated
      hazards (inherent toxicity, eye irritation), thereby increasing operators'
      safety. Perfusion was performed with a peristaltic pump for 20-30 minutes at an
      optimum rate of 0.20 l/min and required only 5 litres of the fixative. The
      specimens were sufficiently hardened to be extracted. High-quality tissues were
      available for histology analysis. This technique offers a user-friendly closed
      system for brain perfusion fixation which can be adapted for other tissues of the
      head, face and neck.

PMID- 29320927
TI  - Benefits of Using High-Volume-Low-Pressure Tracheal Tube in Children Undergoing
      Congenital Cardiac Surgery: Evidence From a Prospective Randomized Study.
AB  - BACKGROUND: In the past 2 decades, usage of high-volume-low-pressure microcuffed
      tracheal tubes in smaller children has increased. However, there is paucity of
      evidence of its usage in smaller children undergoing congenital cardiac surgery.
      The aim of this study was to assess if microcuff endotracheal tubes in neonates
      and younger children undergoing congenital cardiac surgery is associated with
      better outcomes than uncuffed tubes. METHODS: We carried out this single-center,
      prospective, randomized study between June and November 2016. Eighty patients
      were randomized into those receiving microcuff tracheal tubes and conventional
      uncuffed tubes. Primary outcome was stridor postextubation. Secondary outcomes
      measured included number of tube changes, volume of anesthetic gases required,
      and cost incurred. RESULTS: The 2 groups were comparable in terms of baseline
      characteristics and duration of intubation. Incidence of stridor was
      significantly higher in conventional uncuffed tubes (12 [30%] vs 4 [10%]; P =
      .04) and so was the number of tube changes required (17/40 [42.5%] vs 2/40 [5%];
      P <= .001). Tube change was associated with more than 3-fold risk of stridor
      (odds ratio = 3.92; 95% confidence interval = 1.23-12.43). Isoflurane (29.14 +/-
      7.01 mL vs19.2 +/- 4.81 mL; P < .0001) and oxygen flow requirement ( P < .0001)
      and the resultant cost (7.46 +/- 1.4 vs 5.77 +/- 1.2 US$; P < .0001) were all
      significantly higher in the conventional uncuffed group. CONCLUSION: Microcuff
      pediatric tracheal tube is associated with significantly lower incidence of
      stridor, tube changes, and anesthetic gas requirement. This leads to significant
      cost reduction that offsets the higher costs associated with usage of a microcuff
      tracheal tube.

PMID- 29320928
TI  - Interaction of caffeine and sulfadiazine with lysozyme adsorbed at colloidal
      metal nanoparticle interface: influence on drug transport ability and
      antibacterial activity.
AB  - The modulated bioactivity of proteins immobilized on nanoparticle (NP) interfaces
      is of tremendous interest toward designing better therapeutic and diagnostic
      tools. In this work, binding behavior and the antibacterial activity of free
      lysozyme (LYS) as well as its non-covalent assembly with silver (Ag) and gold
      (Au) colloidal NPs were compared in presence of two model drugs, viz.
      sulfadiazine (SDZ) and caffeine (CAF). Intrinsic protein fluorescence was found
      to quench due to the formation drug-protein complex in case of CAF resulting a
      linear Stern-Volmer (SV) plot with KSV = 1.83 * 103 M-1.On the other hand, a
      positive deviation beyond [SDZ] ~0.15 mM is explained due to the formation of a
      fluorophore - quencher sphere with radius of 13.85 +/- 1.80 A that results almost
      one order of magnitude higher KSV (1.75 * 104 M-1). Molecular docking calculation
      also predicts relatively more stabilized complex of SDZ with LYS in comparison to
      CAF (DeltaE ~ 3 kJ mol-1). Synchronous fluorescence results corresponding to Trp
      and Tyr residues as well as FTIR spectra in the amide I region of LYS confirms
      minimal deformation in the LYS secondary structure on adsorption to spherical NP
      surface. Although the nature of LYS-drug interaction remains invariant, the
      extent of quenching interaction as well as the drug binding ability is strongly
      modulated in presence of NPs. Further, the antibacterial activity of LYS in
      presence of the investigated drugs shows 9-14% upsurge with AuNP, in sharp
      contrast to ca. 31-34% decrease in AgNP.

PMID- 29320929
TI  - Metacognitive Reflection as a Moderator of Attitude Strength Versus Attitude
      Bolstering: Implications for Attitude Similarity and Attraction.
AB  - "Strong" attitudes often have greater impact than "weak" attitudes. However,
      emerging research suggests that weak (uncertain) attitudes can substantially
      influence thinking or behavior. We propose metacognitive reflection as a
      moderator between traditional strength patterns and these emerging attitude
      bolstering patterns. Across six studies, research participants encountered a
      target person who agreed or disagreed with participants' attitudes. When focused
      on evaluating the target, attitudes predicted target evaluations better when the
      attitude was held with certainty (Study 1A), or after certainty had been primed
      (Studies 2A and 3; strength effects). However, when engaged in attitudinal social
      comparison (metacognitive reflection), attitudes better predicted target
      evaluation when the attitudes were held with doubt (Study 1B), or after doubt had
      been primed (Studies 2B and 3; bolstering effects). Expected change in certainty
      served as a mediator of attitude effects in metacognitive reflection but not
      target-focus conditions when doubt had been primed (Study 4).

PMID- 29320930
TI  - The Amount and Source of Millionaires' Wealth (Moderately) Predict Their
      Happiness.
AB  - Two samples of more than 4,000 millionaires reveal two primary findings: First,
      only at high levels of wealth-in excess of US$8 million (Study 1) and US$10
      million (Study 2)-are wealthier millionaires happier than millionaires with lower
      levels of wealth, though these differences are modest in magnitude. Second,
      controlling for total wealth, millionaires who have earned their wealth are
      moderately happier than those who inherited it. Taken together, these results
      suggest that, among millionaires, wealth may be likely to pay off in greater
      happiness only at very high levels of wealth, and when that wealth was earned
      rather than inherited.

PMID- 29320931
TI  - Physician decision making in anticoagulating atrial fibrillation: a prospective
      survey of a physician notification system for atrial fibrillation detected on
      cardiac implantable electronic devices of patients at increased risk of stroke.
AB  - OBJECTIVES: The objectives of this study were to evaluate the effectiveness of a
      physician notification system for atrial fibrillation (AF) detected on cardiac
      devices, and to assess predictors of anticoagulation in patients with device
      detected AF. METHODS: In 2013, a physician notification system for AF detected on
      a patient's CIED [including pacemakers, implantable cardioverter defibrillators
      (ICD) or cardiac resynchronization therapy (CRT) devices] was implemented, with a
      recommendation to consider oral anticoagulation in high-risk patients. We
      prospectively investigated the effectiveness of this system, and evaluated both
      patient and physician predictors of anticoagulation, as well as factors
      influencing physician decision making in prescribing anticoagulation. Both uni-
      and multivariable analysis as well as descriptive statistics were used in the
      analysis. RESULTS: We identified 177 patients with device-detected AF, 126 with a
      CHADS2 ?2. Only 41% were prescribed anticoagulation at any point within 12
      months. On multivariable analysis, stroke risk as predicted by CHADS2 was not a
      predictor of anticoagulation. ASA use predicted a lower rate of anticoagulation
      (OR 0.39, 95% CI 0.16-0.97, p = 0.04); physicians in practice for <20 years were
      more likely to prescribe anticoagulation (OR 3.39, 95% CI 1.28-8.93, p = 0.01);
      and physicians who believed both cardiologist and family doctor should be
      involved in managing anticoagulation were more likely to prescribe
      anticoagulation (OR 3.28, 95% CI 1.02-10.5, p = 0.05). CONCLUSIONS: Patients on
      aspirin were less likely to be anticoagulated. Physicians in practice for <20
      years and who believed that both the general practitioner and cardiologist should
      be involved in managing anticoagulants were more likely to prescribe
      anticoagulation.

PMID- 29320932
TI  - Classical molecular dynamics simulation of seryl tRNA synthetase and threonyl
      tRNA synthetase bound with tRNA and aminoacyl adenylate.
AB  - Lacunae of understanding exist concerning the active site organization during the
      charging step of the aminoacylation reaction. We present here a molecular
      dynamics simulation study of the dynamics of the active site organization during
      charging step of subclass IIa dimeric SerRS from Thermus thermophilus (ttSerRS)
      bound with tttRNASer and dimeric ThrRS from Escherichia coli (ecThrRS) bound with
      ectRNAThr. The interactions between the catalytically important loops and tRNA
      contribute to the change in dynamics of tRNA in free and bound states,
      respectively. These interactions help in the development of catalytically
      effective organization of the active site. The A76 end of the tttRNASer exhibits
      fast dynamics in free State, which is significantly slowed down within the active
      site bound with adenylate. The loops change their conformation via multimodal
      dynamics (a slow diffusive mode of nanosecond time scale and fast librational
      mode of dynamics in picosecond time scale). The active site residues of the motif
      2 loop approach the proximal bases of tRNA and adenylate by slow diffusive motion
      (in nanosecond time scale) and make conformational changes of the respective side
      chains via ultrafast librational motion to develop precise hydrogen bond
      geometry. Presence of bound Mg2+ ions around tRNA and dynamically slow bound
      water are other common features of both aaRSs. The presence of dynamically rigid
      Zinc ion coordination sphere and bipartite mode of recognition of ectRNAThr are
      observed.

PMID- 29320933
TI  - Gray matter networks and cognitive impairment in multiple sclerosis.
AB  - BACKGROUND: Coordinated patterns of gray matter morphology can be represented as
      networks, and network disruptions may explain cognitive dysfunction related to
      multiple sclerosis (MS). OBJECTIVE: To investigate whether single-subject gray
      matter network properties are related to impaired cognition in MS. METHODS: We
      studied 148 MS patients (99 female) and 33 healthy controls (HC, 21 female).
      Seven network parameters were computed and compared within MS between cognitively
      normal and impaired subjects, and associated with performance on
      neuropsychological tests in six cognitive domains with regression models.
      Analyses were controlled for age, gender, whole-brain gray matter volumes, and
      education level. RESULTS: Compared to MS subjects with normal cognition, MS
      subjects with cognitive impairment showed a more random network organization as
      indicated by lower lambda values (all p < 0.05). Worse average cognition and
      executive function were associated with lower lambda values. Impaired information
      processing speed, working memory, and attention were associated with lower
      clustering values. CONCLUSION: Our findings indicate that MS subjects with a more
      randomly organized gray matter network show worse cognitive functioning,
      suggesting that single-subject gray matter graphs may capture neurological
      dysfunction due to MS.

PMID- 29320934
TI  - Improving the Care of Youth With Type 1 Diabetes With a Novel Medical-Legal
      Community Intervention: The Diabetes Community Care Ambassador Program.
AB  - Purpose The purpose of this study was to examine the feasibility and efficacy of
      the Diabetes Community Care Ambassador (DCCA) Program, a novel medical-legal
      community intervention designed to support high-risk youth with type 1 diabetes.
      Methods Study eligibility criteria: ages 3-19 years, A1C >=8.5% (>=69 mmol/mol)
      and/or recent diabetic ketoacidosis hospitalization, type 1 diabetes duration >=1
      year, and English- or Spanish-speaking. Eighty-nine youth and their caregivers
      participated in the 9- to 12-month intervention, which included diabetes
      education and support through 3 home visits, 1 to 2 school visits, and phone
      support from a lay health worker, as well as legal support from a medical-legal
      partnership attorney. Feasibility was assessed; change in A1C was compared in a
      linear mixed model. Results Of the 89 DCCA Program participants, 80% completed
      the program, with the majority of participants rating their DCCA favorably. Sixty
      two percent reported >=1 unmet legal need, of whom 29% accepted legal counsel.
      Youth enrolled in the DCCA Program demonstrated an improvement in glycemic
      control as their mean A1C decreased from 9.71% (83 mmol/mol) at the start of the
      program to 9.40% (79 mmol/mol) at the end of the intervention period ( P = .03).
      Participants with public health insurance experienced the greatest differential
      A1C reduction (9.79% to 9.11%, 83 mmol/mol to 76 mmol/mol). Conclusions The DCCA
      Program represents a promising intervention for improving care of high-risk youth
      with type 1 diabetes. A significant proportion of caregivers of youth reported
      having an unmet legal need. Participants remained highly engaged and demonstrated
      improved glycemic control, particularly youth with public health insurance.

PMID- 29320935
TI  - Modified Dorsal Approach in the Management of Lisfranc Injuries.
AB  - BACKGROUND: Open reduction and internal fixation of Lisfranc injuries has
      typically used multiple longitudinal incisions or a single transverse incision to
      approach the tarso-metatarsal joint (TMTJ). The incidence of wound-related
      complications is considerable. We describe a novel single-incision approach that
      utilizes subcutaneous windows to the medial TMTJ. METHODS: A retrospective review
      identified 150 patients who underwent open reduction and internal fixation for
      Lisfranc injuries, via the modified dorsal approach, at our center between
      January 2011 and June 2016. Removal of hardware (ROH) was routinely undertaken in
      105 patients at a median of 210 days postoperatively. Medical records were
      reviewed to record patient demographics, mechanism of injury, and operative
      details. Outpatient notes were reviewed to identify wound-related complications,
      including delayed wound healing, superficial infection, wound dehiscence, deep
      infection, complex regional pain syndrome (CRPS), neuroma, and impaired
      sensation. Median age was 37 years (range, 19-78 years). Seventy-three percent of
      patients (110) were male. Most frequent mechanisms of injury were motor vehicle
      accident (MVA), 39%; motorbike accident (MBA), 19%; and fall, 18%. Sixteen
      percent (24) of injuries were open. Five patients required soft tissue
      reconstruction at the primary operation. Median follow-up was 144 (range, 27-306)
      weeks. RESULTS: Following the primary procedure, 14% of patients experienced
      wound-related complications including delayed healing (3%), superficial infection
      (5%), dehiscence (3%), complex regional pain syndrome (CRPS) (1%), and impaired
      sensation (1%). MBA injuries were at 15.1 times odds of superficial infection ( P
      =.01) than were MVA injuries. Following ROH, 13% of patients experienced wound
      related complications, including delayed healing (2%), superficial infection
      (8%), dehiscence (1%), CRPS (2%), and neuroma (1%). Overall, 5 patients returned
      to surgery for soft tissue reconstruction for wound dehiscence. CONCLUSION: The
      modified dorsal approach using intervals to the midfoot offers a viable
      alternative with comparable wound complication rates to existing midfoot
      approaches. LEVEL OF EVIDENCE: Level IV, case series.

PMID- 29320936
TI  - Role of the Deltoid Ligament in Syndesmotic Instability.
AB  - BACKGROUND: The deltoid ligament (DL) is the principal ligamentous stabilizer of
      the medial ankle joint. Little is known, however, about the contribution of the
      DL toward stabilizing the syndesmosis. The aim of this study was to
      arthroscopically evaluate whether the DL contributes to syndesmotic stability in
      the coronal plane. METHODS: Eight above-knee cadaveric specimens were used in
      this study. A lateral hook test was performed by applying 100 N of lateral force
      to the fibula in the intact state and after sequential transection of the DL,
      anterior-inferior tibiofibular ligament (AITFL), interosseous ligament (IOL), and
      posterior-inferior tibiofibular ligament (PITFL). At each stage, distal
      tibiofibular diastasis was measured arthroscopically at both the anterior and
      posterior third of the incisura and compared to stress measurements of the intact
      syndesmosis. Measurements were performed using probes ranging from 0.1 to 6.0 mm,
      with 0.1-mm increments. RESULTS: There was no significant increase in diastasis
      at either the anterior or posterior third of the tibiofibular articulation after
      isolated DL disruption, nor when combined with AITFL transection. In contrast, a
      significant increase in diastasis was observed following additional disruption of
      the IOL (anterior and posterior third diastasis, P= .012 and .026, respectively),
      and after transection of all 3 syndesmotic ligaments (anterior and posterior
      third diastasis, P=.001 and .001, respectively). CONCLUSION: When evaluating the
      syndesmosis arthroscopically in a cadaveric model under lateral stress, neither
      isolated disruption of the DL nor combined DL and AITFL injuries destabilized the
      syndesmosis in the coronal plane. In contrast, the syndesmosis became unstable if
      the DL was injured in conjunction with partial syndesmotic disruption that
      included the AITFL and IOL. CLINICAL RELEVANCE: Disruption of the DL appeared to
      destabilize the syndesmosis in the coronal plane when associated with partial
      disruption of the syndesmosis (AITFL and IOL).

PMID- 29320937
TI  - Radiographic Measurements Associated With the Natural Progression of the Hallux
      Valgus During at Least 2 Years of Follow-up.
AB  - BACKGROUND: This study aimed to investigate the radiographic measurements
      associated with the progression of hallux valgus during at least 2 years of
      follow-up. METHODS: Seventy adult patients with hallux valgus who were followed
      for at least 2 years and underwent weightbearing foot radiography were included.
      Radiographic measurements included the hallux valgus angle (HVA), hallux
      interphalangeal angle, intermetatarsal angle (IMA), metatarsus adductus angle,
      distal metatarsal articular angle (DMAA), tibial sesamoid position,
      anteroposterior (AP) talo-first metatarsal angle, and lateral talo-first
      metatarsal angle. Patients were divided into progressive and nonprogressive
      groups. Binary logistic regression analysis was performed to identify factors
      that significantly affected the progression of hallux valgus deformity. The
      correlation between change in HVA and changes in other radiographic indices
      during follow-up was analyzed. RESULTS: The DMAA ( P = .027) and AP talo-first
      metatarsal angle ( P = .034) at initial presentation were found to be significant
      factors affecting the progression of hallux valgus deformity. Change in the HVA
      during follow-up was significantly correlated with changes in the IMA ( r =
      0.423; P = .001) and DMAA ( r = 0.541; P < .001). CONCLUSION: The change in the
      HVA was found to be significantly correlated with changes in the IMA and DMAA. A
      future study is required to elucidate whether this correlation can be explained
      by the progressive instability of the first tarsometatarsal joint. We believe
      special attention needs to be paid to patients with pes planus and increased
      DMAA. LEVEL OF EVIDENCE: Level III, comparative study.

PMID- 29320938
TI  - Diagnosing Prosopagnosia: The Utility of Visual Noise in the Cambridge Face
      Recognition Test.
AB  - Adding visual noise to facial images has been used to increase reliance on
      configural processing. Whether this enhances the ability of tests to diagnose
      prosopagnosia is not known. We examined 15 subjects with developmental
      prosopagnosia, 13 subjects with acquired prosopagnosia, and 38 control subjects
      with the Cambridge Face Memory Test. We compared their performance on the second
      phase, without visual noise, and on the third phase, which adds visual noise. We
      analyzed the results with signal detection theory methods. The performance of
      controls worsened more than did that of prosopagnosic subjects when noise was
      added. The second phase showed better ability to discriminate between
      prosopagnosic and control subjects than did the third phase. For developmental
      prosopagnosia, a test using only the 48 trials of the first and second phases
      yielded sensitivity of 88% and specificity of 91% with a criterion of 33/48
      correct, performance characteristics that are similar for a criterion of 43/72
      for the whole test. We conclude that a shortened Cambridge Face Memory Test
      without the noisy images may be a quicker yet equally effective instrument for
      diagnosing prosopagnosia. The theoretical advantage of noisy images is outweighed
      by the poorer performance of control subjects with visual noise.

PMID- 29320939
TI  - New York State's COSH Movement: A Brief History.
AB  - Unions, health and safety activists, and professionals came together to create
      Coalitions for Occupational Safety and Health (COSH groups) in a number of cities
      across the United States beginning in the 1970s. The COSHes have played an
      important and unique role in advocating worker health and safety since that time,
      through activities including technical assistance, training and education, and
      campaigns on workplace and public policies. In New York State, activist
      coalitions created eight COSH groups distributed around the state. This paper
      presents a history of New York's COSHes based on interviews with key
      participants. The interviews shed light on the origins of the COSH movement in
      New York, the development and activities of the COSHes, and the organizational
      trajectory of individual New York COSHes in response to both extra and
      intraorganizational challenges. Participants' accounts of these issues may be
      useful for those seeking to sustain the COSH movement.

PMID- 29320940
TI  - Methylation-mediated loss of SFRP2 enhances invasiveness of non-small cell lung
      cancer cells.
AB  - The malignancy of non-small cell lung cancer (NSCLC) largely results from its
      invasive manner. Secreted frizzled-related proteins (SFRPs) have been recently
      found to suppress the invasiveness of some cancers. On the other hand, the
      methylation of SFRPs increases protein degradation to reduce the activity of
      SFRPs, resulting in increased tumor cell invasion and cancer metastasis. However,
      the role of SFRPs in the invasion of NSCLC has not been reported. Here we
      analyzed the regulation of SFRPs in NSCLC cells and its effects on cell invasion.
      We found that SFRP2 mRNA was significantly decreased and methylation of SFRP2
      gene was significantly increased in NSCLC tissue, compared to the paired adjacent
      nontumor tissue. Moreover, SFRP2 expression was significantly decreased in NSCLC
      cell lines. In NSCLC cell lines, the SFRP2 expression would be restored by the
      demethylation of SFRP2 gene with 5'-aza-deoxycytidine in NSCLC cell lines, at the
      levels of both mRNA and protein. Thus, the cell invasion would be suppressed.
      Furthermore, the demethylation of SFRP2 gene appeared to inhibit Zinc Finger E
      Box Binding Homeobox 1 (ZEB1) and matrix metallopeptidase 9 (MMP9), two key
      factors that enhance NSCLC cell invasion. Thus, SFRP2 may inhibit NSCLC invasion
      by suppressing ZEB1 and MMP9, while its methylation promotes NSCLC invasion.

PMID- 29320942
TI  - Campus Sexual Assault: Future Directions for Research.
AB  - Campus sexual assault (CSA) has received unprecedented attention over recent
      years, resulting in an abundance of federal guidance and mandates. In response,
      efforts to address and prevent CSA at Institutions of Higher Education (IHE)
      across the country have grown quickly, including the development and
      implementation of programs and policies. Because the changes on campuses have
      occurred at such a rapid pace, a number of gaps exist within the field of CSA
      research. To ensure that changes on IHE are evidence-based, there is a need to
      review the existing research available and the inquiry still needed, based on key
      areas outlined in federal guidance, the expressed needs of campus community
      members, survivors, and students who commit sexual offenses on college campuses.
      The purpose of this review is to summarize the empirical research related to CSA
      gained from the past two decades and identify areas in which further work is
      needed, specifically related to key areas identified in recent guidance provided
      to IHE. This article concludes with guidance for research moving forward to help
      strengthen response and prevention efforts.

PMID- 29320941
TI  - Progressive delayed respiratory complications of sulfur mustard poisoning in 43
      Iranian veterans, three decades after exposure.
AB  - The most common delayed complication of sulfur mustard (SM) poisoning has been
      observed in the respiratory tracts. It was thus aimed to investigate the delayed
      respiratory complications in SM-exposed patients around 25 years before the
      study. Forty-three veterans with more than 25% disability of due to SM poisoning
      were investigated. Clinical examinations as well as pulmonary function test (PFT)
      were performed. High-resolution computed tomography (HRCT) of the lungs was done
      as clinically indicated. Triad of chronic cough, dyspnea, and expectoration were
      the most common symptoms that were recorded in 88.2%, 88.2%, and 64.7% of the
      patients, respectively. PFT abnormalities were detected in 44.18% of the
      patients. Restrictive pattern was the most common (41.86%), while pure
      obstructive pattern did not detect at all. Mixed pattern was significantly
      correlated with higher disability percentages among the veterans ( p < 0.001).
      Significant reverse correlation between the disability percentages and forced
      expiratory volume in 1 s/forced vital capacity ratio was obtained ( p = 0.010, r
      = -0.389). Air trapping was the most common abnormality in HRCTs (50%).
      Bronchiectasis (25%), pulmonary fibrosis (25%), and ground-glass attenuation
      (16.66%) were other common HRCT findings. Comparing with the previous studies on
      these patients, more restrictive and mixed pattern were observed. Moreover,
      bronchiolitis, bronchiectasis, and lung fibrosis were the main pathological
      findings in these patients.

PMID- 29320943
TI  - Management training in global health education: a Health Innovation Fellowship
      training program to bring healthcare to low-income communities in Central
      America.
AB  - BACKGROUND: Interprofessional education is increasingly recognized as essential
      for health education worldwide. Although effective management, innovation, and
      entrepreneurship are necessary to improve health systems, business schools have
      been underrepresented in global health education. Central America needs more
      health professionals trained in health management and innovation to respond to
      health disparities, especially in rural communities. OBJECTIVE: This paper
      explores the impact of the Health Innovation Fellowship (HIF), a new training
      program for practicing health professionals offered jointly by the Central
      American Healthcare Initiative and INCAE Business School, Costa Rica. Launched in
      2014, HIF's goal is to create a network of highly trained interdisciplinary
      health professionals in competencies to improve health of Central American
      communities through better health management. METHODS: The program's fellows
      carried out innovative healthcare projects in their local regions. The first
      three annual cohorts (total of 43 fellows) represented all health-related
      professions and sectors (private, public, and civil society) from six Central
      American countries. All fellows attended four 1-week, on-site modular training
      sessions, received ongoing mentorship, and stayed connected through formal and
      informal networks and webinars through which they exchange knowledge and support
      each other. CAHI stakeholders supported HIF financially. RESULTS: Impact
      evaluation of the three-year pilot training program is positive: fellows improved
      their health management skills and more than 50% of the projects found either
      financial or political support for their implementation. CONCLUSIONS: HIF's
      strengths include that both program leaders and trainees come from the Global
      South, and that HIF offers a platform to collaborate with partners in the Global
      North. By focusing on promoting innovation and management at a top business
      school in the region, HIF constitutes a novel capacity-building effort within
      global health education. HIF is a capacity-building effort that can be scaled up
      in the region and other low- and middle-income countries.

PMID- 29320945
TI  - The Influence of Exercise Dosing on Outcomes in Patients With Knee Disorders: A
      Systematic Review.
AB  - Study Design Systematic review. Background Therapeutic exercise is commonly used
      to treat individuals with knee disorders, but dosing parameters for optimal
      outcomes are unclear. Large variations exist in exercise prescription, and
      research related to specific dosing variables for knee osteoarthritis, patellar
      tendinopathy, and patellofemoral pain is sparse. Objectives To identify specific
      doses of exercise related to improved outcomes of pain and function in
      individuals with common knee disorders, categorized by effect size. Methods Five
      electronic databases were searched for studies related to exercise and the 3
      diagnoses. Means and standard deviations were used to calculate effect sizes for
      the exercise groups. The overall quality of evidence was assessed using the
      Physiotherapy Evidence Database scale. Results Five hundred eighty-three studies
      were found after the initial search, and 45 were included for analysis after
      screening. Physiotherapy Evidence Database scale scores were "fair" quality and
      ranged from 3 to 8. For knee osteoarthritis, 24 total therapeutic exercise
      sessions and 8- and 12-week durations of exercise were parameters most often
      associated with large effects. An exercise frequency of once per week was
      associated with no effect. No trends were seen with exercise dosing for patellar
      tendinopathy and patellofemoral pain. Conclusion This review suggests that there
      are clinically relevant exercise dosing variables that result in improved pain
      and function for patients with knee osteoarthritis, but optimal dosing is still
      unclear for patellar tendinopathy and patellofemoral pain. Prospective studies
      investigating dosing parameters are needed to confirm the results from this
      systematic review. Level of Evidence Therapy, level 1a. J Orthop Sports Phys Ther
      2018;48(3):146-161. Epub 10 Jan 2018. doi:10.2519/jospt.2018.7637.

PMID- 29320944
TI  - Effects of Varying Reverberation on Music Perception for Young Normal-Hearing and
      Old Hearing-Impaired Listeners.
AB  - Reverberation enhances music perception and is one of the most important acoustic
      factors in auditorium design. However, previous research on reverberant music
      perception has focused on young normal-hearing (YNH) listeners. Old hearing
      impaired (OHI) listeners have degraded spatial auditory processing; therefore,
      they may perceive reverberant music differently. Two experiments were conducted
      examining the effects of varying reverberation on music perception for YNH and
      OHI listeners. Experiment 1 examined whether YNH listeners and OHI listeners
      prefer different amounts of reverberation for classical music listening.
      Symphonic excerpts were processed at a range of reverberation times using a point
      source simulation. Listeners performed a paired-comparisons task in which they
      heard two excerpts with different reverberation times, and they indicated which
      they preferred. The YNH group preferred a reverberation time of 2.5 s; however,
      the OHI group did not demonstrate any significant preference. Experiment 2
      examined whether OHI listeners are less sensitive to (e, less able to
      discriminate) differences in reverberation time than YNH listeners. YNH and OHI
      participants listened to pairs of music excerpts and indicated whether they
      perceived the same or different amount of reverberation. Results indicated that
      the ability of both groups to detect differences in reverberation time improved
      with increasing reverberation time difference. However, discrimination was poorer
      for the OHI group than for the YNH group. This suggests that OHI listeners are
      less sensitive to differences in reverberation when listening to music than YNH
      listeners, which might explain the lack of group reverberation time preferences
      of the OHI group.

PMID- 29320946
TI  - Cognitive Demands Influence Lower Extremity Mechanics During a Drop Vertical Jump
      Task in Female Athletes.
AB  - Study Design Cross-sectional study. Background The drop vertical jump task is
      commonly used to screen for anterior cruciate ligament injury risk; however, its
      predictive validity is limited. The limited predictive validity of the drop
      vertical jump task may be due to not imposing the cognitive demands that reflect
      sports participation. Objectives To investigate the influence of additional
      cognitive demands on lower extremity mechanics during execution of the drop
      vertical jump task. Methods Twenty uninjured women (age range, 18-25 years) were
      required to perform the standard drop vertical jump task, as well as drop
      vertical jumps that included additional cognitive demands. The additional
      cognitive demands were related to attending to an overhead goal (ball suspended
      overhead) and/or temporal constraints on movement selection (decision making).
      Three-dimensional ground reaction forces and lower extremity mechanics were
      compared between conditions. Results The inclusion of the overhead goal resulted
      in higher peak vertical ground reaction forces and lower peak knee flexion angles
      in comparison to the standard drop vertical jump task. In addition, participants
      demonstrated greater peak knee abduction angles when trials incorporated temporal
      constraints on decision making and/or required participants to attend to an
      overhead goal, in comparison to the standard drop vertical jump task. Conclusion
      Imposing additional cognitive demands during execution of the drop vertical jump
      task influenced lower extremity mechanics in a manner that suggested increased
      loading of the anterior cruciate ligament. Tasks utilized in anterior cruciate
      ligament injury risk screening may benefit from more closely reflecting the
      cognitive demands of the sports environment. J Orthop Sports Phys Ther
      2018;48(5):381-387. Epub 10 Jan 2018. doi:10.2519/jospt.2018.7739.

PMID- 29320947
TI  - From global-to-local: rural mental health in South Africa.
AB  - In this paper, the current situation regarding rural mental health in South
      Africa is explored. The current status is presented, followed by an attempt to
      provide approaches and ideas to improve the situation in order to make it more
      context appropriate and relevant. Issues of staffing, task shifting or sharing,
      and formal vs informal health care systems are considered and discussed as
      possible future approaches to improve rural mental health care in South Africa.

PMID- 29320949
TI  - Absorption, distribution, metabolism and excretion of an isocitrate dehydrogenase
      2 inhibitor enasidenib in rats and humans.
AB  - 1. The absorption, distribution, metabolism and excretion of enasidenib were
      studied following a single oral dose of [14C]enasidenib to rats (10 mg/kg; 100
      MUCi/kg) and healthy volunteers (100 mg; 318 nCi). 2. Enasidenib was readily
      absorbed, extensively metabolized and primarily eliminated via the hepatobiliary
      pathway. Enasidenib-derived radioactivity was widely distributed in rats.
      Excretion of radioactivity was approximately 95-99% of the dose from rats in 168
      h post-dose and 82.4% from human volunteers in 504 h post-dose. In rat bile,
      approximately 35-42% of the administered dose was recovered, with less than 5% of
      the dose excreted as the parent drug. Renal elimination was a minor pathway, with
      <12% of the dose excreted in rat urine and <10% of the dose excreted in human
      urine. 3. Enasidenib was the prominent radioactive component in rat and human
      systemic circulation. Enasidenib was extensively metabolized in rats and human
      volunteers through N-dealkylation, oxidation, direct glucuronidation and
      combinations of these pathways. Glucuronidation was the major metabolic pathway
      in rats while N-dealkylation was the prominent metabolic pathway in human
      volunteers. All human metabolites were detected in rats.

PMID- 29320950
TI  - Reclaim the Menopause: A pilot study of an evidence-based menopause course for
      symptom management and resilience building.
AB  - Reclaim the Menopause is a community-based menopause course developed by Hands
      Inc. and supported by Hackney Learning Trust. The course provides evidence-based
      education, cognitive behaviour therapy and psychosocial support to promote
      menopause awareness, challenge stigma and increase self-management amongst
      menopausal women. Ethnicity was an important aspect of the work, as Hands Inc.
      was keen to reach women who might not otherwise access interventions. All course
      participants were Black British (as were two of the three facilitators). Course
      attendees reported reduced menopausal symptoms as well as improvements in mood
      and the quality of their lives.

PMID- 29320951
TI  - Glutathione conjugated polyethylenimine on the surface of Fe3O4 magnetic
      nanoparticles as a theranostic agent for targeted and controlled curcumin
      delivery.
AB  - Theranostics with the ability to simultaneous monitoring of treatment progress
      and controlled delivery of therapeutic agents has become as an emerging
      therapeutic paradigm in cancer therapy. In this study, we have developed a novel
      surface functionalized iron oxide nanoparticle using polyethyleneimine and
      glutathione for targeted curcumin (CUR) delivery and acceptable pH sensitive
      character. The developed magnetic nanoparticles (MNPs) were physicochemically
      characterized by FT-IR, XRD, FE-SEM and TEM. The MNPs was obtained in spherical
      shape with diameter of 50 nm. CUR was efficiently loaded into the MNPs and then
      in vitro release analyses were evaluated and showed that the prepared MNPs could
      release higher amount of CUR in acidic medium compared to neutral medium due to
      the pH sensitive property of the coated polymer. MTT assay confirmed the superior
      toxicity of CUR loaded MNPs compared to the control nanoparticles. Higher
      cellular uptake of the MNPs than negative control cells was demonstrated in SK-N
      MC cell line. In vitro assessment of MRI properties showed that synthesized MNPs
      could be used as MRI imaging agent. Furthermore, according to hemolysis assay,
      the developed formulation exhibited suitable hemocompatibility. In vivo blood
      circulation analysis of the MNPs also exhibited enhanced serum bioavailability up
      to 2.5 fold for CUR loaded MNPs compared with free CUR.

PMID- 29320953
TI  - Spaceflight Activates Protein Kinase C Alpha Signaling and Modifies the
      Developmental Stage of Human Neonatal Cardiovascular Progenitor Cells.
AB  - Spaceflight impacts cardiovascular function in astronauts; however, its impact on
      cardiac development and the stem cells that form the basis for cardiac repair is
      unknown. Accordingly, further research is needed to uncover the potential
      relevance of such changes to human health. Using simulated microgravity (SMG)
      generated by two-dimensional clinorotation and culture aboard the International
      Space Station (ISS), we assessed the effects of mechanical unloading on human
      neonatal cardiovascular progenitor cell (CPC) developmental properties and
      signaling. Following 6-7 days of SMG and 12 days of ISS culture, we analyzed
      changes in gene expression. Both environments induced the expression of genes
      that are typically associated with an earlier state of cardiovascular
      development. To understand the mechanism by which such changes occurred, we
      assessed the expression of mechanosensitive small RhoGTPases in SMG-cultured CPCs
      and observed decreased levels of RHOA and CDC42. Given the effect of these
      molecules on intracellular calcium levels, we evaluated changes in noncanonical
      Wnt/calcium signaling. After 6-7 days under SMG, CPCs exhibited elevated levels
      of WNT5A and PRKCA. Similarly, ISS-cultured CPCs exhibited elevated levels of
      calcium handling and signaling genes, which corresponded to protein kinase C
      alpha (PKCalpha), a calcium-dependent protein kinase, activation after 30 days.
      Akt was activated, whereas phosphorylated extracellular signal-regulated kinase
      levels were unchanged. To explore the effect of calcium induction in neonatal
      CPCs, we activated PKCalpha using hWnt5a treatment on Earth. Subsequently, early
      cardiovascular developmental marker levels were elevated. Transcripts induced by
      SMG and hWnt5a-treatment are expressed within the sinoatrial node, which may
      represent embryonic myocardium maintained in its primitive state. Calcium
      signaling is sensitive to mechanical unloading and directs CPC developmental
      properties. Further research both in space and on Earth may help refine the use
      of CPCs in stem cell-based therapies and highlight the molecular events of
      development.

PMID- 29320952
TI  - Fatty acid binding protein-4 is associated with disability in multiple sclerosis
      patients.
AB  - BACKGROUND: Increased adiposity is a risk factor for multiple sclerosis (MS) and
      is associated with increased disability scores. Adipokines may mediate the
      effects of adiposity on MS disease course. OBJECTIVE: The objective of this study
      is to examine the association between the adipokines (leptin and fatty acid
      binding protein-4, FABP4) and clinical course in individuals with MS. METHODS:
      Subjects (18-65 years) with relapsing-remitting MS or clinically isolated
      syndrome and <10 year disease duration were selected from a longitudinal clinical
      study. Cross-sectional and longitudinal models assessed the relationship between
      two adipokines (leptin and FABP4) and disease severity in women and men,
      adjusting for age, disease duration and disease type, Vitamin D level,
      testosterone level, and as well by body mass index (BMI). RESULTS: Mean age of
      subjects ( N = 163, 56% women) was 39.3 years. Higher FABP4 levels were
      associated with higher Expanded Disability Status Scale (EDSS) scores in women in
      both univariate and multivariate analyses (odds ratio: 1.30; p = 0.005). In men,
      higher FABP4 level was significantly associated with change in EDSS over time
      (estimate: 0.0062; p = 0.035). We found no association of FABP4 levels with time
      to next relapse or a measure of processing speed. CONCLUSION: FABP4 levels may be
      associated with increased disability in both men and women with MS independent of
      effects of BMI and other hormones. Future studies should expand these analyses
      and further explore downstream mechanisms of adiposity-related effects in MS.

PMID- 29320954
TI  - The value of fixed rasburicase dosing versus weight-based dosing in the treatment
      and prevention of tumor lysis syndrome.
AB  - Background Rasburicase is a recombinant urate oxidase enzyme used for the
      treatment and prevention of tumor lysis syndrome. Our objective was to assess the
      efficacy of indication-based, low-dose rasburicase administration compared to the
      Food and Drug Administration-approved weight-based dosing. Methods This was a
      retrospective cohort study utilizing data from a tertiary medical center
      including patients admitted from 2012 to 2016, who received at least one dose of
      rasburicase. The primary outcome was achieving a uric acid level less than 7.5
      mg/dl after a single dose of rasburicase in the preprotocol (Food and Drug
      Administration-approved weight-based dosing) and postprotocol (indication-based,
      low-dose) groups. Secondary outcomes included the change in uric acid levels
      between the pre- and postprotocol groups, adherence to the new institutional
      protocol, need for repeat rasburicase doses, and a cost analysis. Results Sixty
      four patients received at least one dose of rasburicase between 1 January 2012
      and 1 December 2016. Twenty-seven (79.4%) doses in the preprotocol group and 28
      (82.4%) doses in the postprotocol group successfully achieved a uric acid level
      less than 7.5 mg/dl after a single dose of rasburicase (p=1.000). The average
      total monthly cost of rasburicase was reduced by 59.9% after adoption of the new
      protocol. Conclusions Indication-based, low-dose rasburicase displayed
      significantly more value when compared to weight-based dosing as shown by
      achieving cost savings without compromising clinical efficacy.

PMID- 29320955
TI  - Therapeutic Roles of Statins in Gynecology and Obstetrics: The Current Evidence.
AB  - INTRODUCTION: Statins are a class of drugs, which act by inhibiting the rate
      limiting enzyme of cholesterol biosynthesis (3-hydroxy-3-methyl-glutaryl-CoA
      reductase). The inhibition of mevalonate synthesis leads to subsequent inhibition
      of downstream products of this pathway, which explains the pleiotropic effects of
      these agents in addition to their well-known lipid-lowering effects. Accumulating
      evidence suggests that statins might be beneficial in various obstetric and
      gynecologic conditions. METHODS: Literature searches were performed in PubMed and
      EMBASE for articles with content related to statins in obstetrics and gynecology.
      The findings are hereby reviewed and discussed. RESULTS: Inhibition of mevalonate
      pathway leads to subsequent inhibition of downstream products such as geranyl
      pyrophosphate, farnesyl pyrophosphate, and geranylgeranyl pyrophosphate. These
      products are required for proper intracellular localization of several proteins,
      which play important roles in signaling pathways by regulating membrane
      trafficking, motility, proliferation, differentiation, and cytoskeletal
      organization. The pleiotropic effects of statins can be summarized in 4
      categories: antiproliferative, anti-invasive, anti-inflammatory, and
      antiangiogenic. The growing body of evidence is promising for these agents to be
      beneficial in endometriosis, polycystic ovary syndrome, adhesion prevention,
      ovarian cancer, preeclampsia, and antiphospholipid syndrome. Although in vivo
      studies showed varying degrees of benefit on fibroids and preterm birth,
      appropriately designed clinical trials are needed to make definitive conclusions.
      CONCLUSION: Statins might play a role in the treatment of endometriosis,
      polycystic ovary syndrome, adhesion prevention, ovarian cancer, preeclampsia, and
      antiphospholipid syndrome.

PMID- 29320948
TI  - The profiles of soluble adhesion molecules in the "great obstetrical syndromes".
AB  - OBJECTIVE: The objective of this study was to determine the profiles of maternal
      plasma soluble adhesion molecules in patients with preeclampsia, small-for
      gestational-age (SGA) fetuses, acute pyelonephritis, preterm labor with intact
      membranes (PTL), preterm prelabor rupture of the membranes (preterm PROM), and
      fetal death. MATERIALS AND METHODS: A cross-sectional study was conducted to
      determine maternal plasma concentrations of sE-selectin, sL-selectin, and sP
      selectin as well as sICAM-1, sVCAM-1, and sPECAM-1 in patients with (1) an
      uncomplicated pregnancy (control, n = 100); (2) preeclampsia (n = 94); (3) SGA
      fetuses (in women without preeclampsia/hypertension, n = 45); (4) acute
      pyelonephritis (n = 25); (5) PTL (n = 53); (6) preterm PROM (n = 24); and (7)
      fetal death (n = 34). Concentrations of soluble adhesion molecules and
      inflammatory cytokines (tumor necrosis factor (TNF)-alpha and interleukin (IL)-8)
      were determined with sensitive and specific enzyme-linked immunoassays. RESULTS:
      In comparison to women with a normal pregnancy, (1) women with preeclampsia had
      higher median concentrations of sE-selectin, sP-selectin, and sVCAM-1, and a
      lower concentration of sL-selectin (all p values < .001); (2) patients with SGA
      fetuses had higher median concentrations of sE-selectin, sP-selectin, and sVCAM-1
      (all p values < .05); (3) patients with a fetal death had higher median
      concentrations of sE-selectin and sP-selectin (all p values < .05); (4) patients
      with acute pyelonephritis had higher median plasma concentrations of sE-selectin,
      sICAM-1, and sVCAM-1 (all p values < .001); (5) patients with preeclampsia and
      acute pyelonephritis, plasma concentrations of sVCAM-1, sE-selectin, and sP
      selectin correlated with those of the proinflammatory cytokines TNF-alpha and
      interleukin (IL)-8 (all p values < .05); (6) patients with PTL had a higher
      median concentration of sP-selectin and a lower median concentration of VCAM-1
      (all p values < .05); and (7) women with preterm PROM had lower median
      concentrations of sL-selectin and sVCAM-1 (all p values < .05). CONCLUSIONS: The
      results of this study show that endothelial cell activation/dysfunction reflected
      by the plasma concentration of sE-selectin is not specific to preeclampsia but is
      present in pregnancies complicated by SGA fetuses, acute pyelonephritis, and
      fetal death. Collectively, we report that each obstetrical syndrome appears to
      have a stereotypical profile of soluble adhesion molecules in the peripheral
      circulation.

PMID- 29320956
TI  - Transvaginal Elastosonography as an Imaging Technique for Diagnosing Adenomyosis.
AB  - To test the hypothesis that the lesional stiffness as measured by transvaginal
      elastosonography (TVESG) correlates with the extent of fibrosis in adenomyotic
      (AM) lesions, and thus TVESG can be used to diagnose AM, we conducted 2 studies.
      The first evaluated the relationship, if any, between lesional stiffness and
      lesional histology in 35 women with histologically confirmed AM in comparison
      with tissue stiffness in 11 control myometrial (CM) and 8 uterine fibroids (UFs)
      tissue samples. The second validated the relationship between lesional stiffness
      and the severity of dysmenorrhea and the amount of menses in AM patients by
      recruiting 112 patients diagnosed with AM, 67 with UF, and 130 controls.
      Transvaginal ultrasound and TVESG were both performed. We found that the
      stiffness of AM lesions was significantly higher than that of UF, which, in turn,
      was significantly higher than that of CM. Lesional stiffness correlated
      positively with uterine size and the extent of lesional fibrosis but negatively
      with E-cadherin and progesterone receptor expression levels. Lesional stiffness
      also correlated with the severity of dysmenorrhea as well as the amount of
      menses. Thus, TVESG can improve the diagnostic accuracy for AM, especially in
      differential diagnosis of AM from UF. The correlation between lesional stiffness
      and the extent of fibrosis and hormonal receptor expression and the severity of
      symptomology strongly suggests that TVESG not only can provide an instant
      assessment of the developmental stage of AM lesions but also may be used to guide
      the choice of the best treatment modality for the patient.

PMID- 29320957
TI  - Cardiovascular and Metabolic Health of 74 Children From Women Previously
      Diagnosed With Polycystic Ovary Syndrome in Comparison With a Population-Based
      Reference Cohort.
AB  - Women with polycystic ovary syndrome (PCOS) have compromised cardiovascular
      health profiles and an increased risk of pregnancy complications. In order to
      evaluate potential consequences, we aim to compare the cardiovascular and
      metabolic health of the children from women with PCOS with a population-based
      reference cohort. We included children from women with PCOS between the age of
      2.5 to 4 years (n = 42) and 6 to 8 years (n = 32). The reference groups consisted
      of 168 (3-4 years old) and 130 children (7-8 years old). In an extensive
      cardiovascular screening program, we measured anthropometrics and blood pressure
      (all children), heart function and vascular rigidity (young children), metabolic
      laboratory assessment and carotid intima thickness (old age-group). Results
      showed that young PCOS offspring have a significantly lower diastolic blood
      pressure (beta = 2.3 [95% confidence interval, CI: 0.5-4.0]) and higher aortic
      pulse pressure (beta = -1.4 [95% CI: -2.5 to -0.2]), compared to the reference
      population. Furthermore, a higher left ventricle internal diameter but a lower
      tissue Doppler imaging of the right wall in systole compared to the reference
      group was found. Older offspring of women with PCOS presented with a
      significantly lower breast and abdominal circumference, but higher triglycerides
      (beta = -0.1 [95% CI: -0.2 to -0.1]), LDL-cholesterol (beta = -0.4 [95% CI: -0.6
      to -0.1]), and higher carotid intima-media thickness (beta = -31.7 [95% CI: -46.6
      to -16.9]) compared to the reference group. In conclusion, we observe subtle but
      distinct cardiovascular and metabolic abnormalities already at an early age in
      PCOS offspring compared to a population-based reference group, despite a lower
      diastolic blood pressure, breast, and abdominal circumference. These preliminary
      findings require confirmation in independent data sets.

PMID- 29320958
TI  - Great Debates in Vascular Medicine: Should all inferior vena cava (IVC) filters
      be removed?

PMID- 29320960
TI  - 39th Annual Meeting of the Society for Medical Decision Making Pittsburgh,
      Pennsylvania, October 22-25, 2017.

PMID- 29320959
TI  - Factor V Leiden paradox in a middle-aged Swedish population: A prospective study.
AB  - Few prospective studies have examined the factor V paradox: factor V Leiden (FVL)
      is a stronger risk factor for deep venous thrombosis (DVT) than for pulmonary
      embolism (PE). The present study, to the best of our knowledge, is the first
      population-based study aimed to examine the relationship between FVL and
      incidence of venous thromboembolism (VTE), DVT and PE in a prospective cohort
      study of middle-aged Swedish individuals. FVL was determined in 4890 subjects
      (aged 46-68 years, 57% women) from the general population without previous VTE or
      cancer, who participated in the Malmo Diet and Cancer study between 1991 and
      1994. Incident cases of VTE were identified from the Swedish patient register
      during a mean follow-up of 15.6 years. Of 4890 subjects with determination of FVL
      (10.2% carriers), 220 had VTE during follow-up (113 DVT, 78 PE, 29 both).
      Incidence of VTE was significantly higher in subjects with heterozygous and
      homozygous FVL: adjusted hazard ratios (HR) were 1.8 (95% CI 1.3-2.6, p=0.001)
      and 6.5 (2.1-21, p=0.001), respectively. The population attributable fraction was
      8.7% for FVL. Adjusted HRs for DVT were 2.2 (1.4-3.3, p<0.001) for heterozygotes
      and 3.3 (0.5-24, p=0.233) for homozygotes. Adjusted HRs for PE were 1.2 (0.65
      2.2, p=0.582) for heterozygotes and 8.7 (2.1-36, p=0.003) for homozygotes. The
      FVL paradox was confirmed for heterozygotes for FVL. However, homozygotes for FVL
      had a high risk for PE, suggesting that the FVL paradox is related to the
      carriership of one wild type and one mutated factor V allele.

PMID- 29320962
TI  - Replantation and revascularization of amputated upper limb appendages outcome and
      predicting the factors influencing the success rates of these procedures in a
      tertiary hospital: An 8-year retrospective, cross-sectional study.
AB  - PURPOSE: Worldwide advances in microsurgery have made salvaging of amputated hand
      via replantation and revascularization common procedures. The present study
      examines the outcome of these procedures in a tertiary hospital in Malaysia.
      METHODS: Patients with hand amputation who underwent replantation or
      revascularization from 2005 to 2012 were identified and reviewed for patient
      characteristics, amputation characteristics and survival rates. Successfully
      treated patients were interviewed to assess the functional outcome using Quick
      Disability of the Arm, Shoulder and Hand (Quick-DASH) questionnaire and Michigan
      Hand Outcome Questionnaire (MHQ). Statistical analysis was performed to evaluate
      outcome and elicit predictive factors. RESULTS: Fifty-five patients were
      enrolled: 37 (67.3%) underwent replantation and 18 (32.7%) underwent
      revascularization. The overall success rate of 78% ( n = 43) was within the range
      of previously reported data (61.6% to 96.0%). Ischaemic time <6 h provided
      significantly better survival rates ( p < 0.05). Functional outcomes were
      successfully assessed in 34 patients (79%), at a mean follow-up of 40 months
      (range 11-93 months). The overall Quick-DASH and MHQ scores were 42.82 +/- 23.69
      and 60.94 +/- 12.82, respectively. No previous reports of functional outcome were
      available for comparison. Both Quick-DASH ( p = 0.001) and MHQ scores ( p <
      0.001) were significantly higher for finger injuries, followed by thumb, wrist
      and palm injuries. CONCLUSION: Ischaemic time and level of injury are important
      predictors of success rate of replantation and revascularization of amputated
      upper limb appendages.

PMID- 29320963
TI  - Long-term clinical and radiographic results of the cementless Spotorno stem in
      Japanese patients: A more than 15-year follow-up.
AB  - PURPOSE: Although previous studies have reported encouraging results of
      cementless Spotorno (CLS) stem, studies with more than 15 years of follow-up are
      rare. The objective of this study is to investigate the long-term results of CLS
      stem and the factors potentially influencing the outcomes. METHODS: The clinical
      and radiographic data of 79 hips (64 patients) were reviewed. Clinical outcome
      was determined using the Japanese Orthopedic Association's hip scoring system
      (JOA hip score). Survival rate was assessed by Kaplan-Meier survival analysis.
      The main end point for survival analysis was revision of stem. The correlations
      between patient demographics, radiographic factors, and stem survival rates were
      analyzed. RESULTS: At a mean follow-up period of 20.1 years, the mean JOA hip
      score at final follow-up was 84.7 points. Stem survival rate for all revisions
      was 97.5% at 20 years, and stem survival for aseptic loosening was 98.9%. Varus
      alignment had a significant negative influence on the survival of the femoral
      stem. CONCLUSION: This study demonstrates acceptable long-term clinical and
      radiographic results of the CLS stem in Japanese patients. Caution should be
      exercised to avoid varus stem alignment.

PMID- 29320964
TI  - Autologous US-guided PRP injection versus US-guided focal extracorporeal shock
      wave therapy for chronic lateral epicondylitis: A minimum of 2-year follow-up
      retrospective comparative study.
AB  - PURPOSE: To compare the efficacy of two independent groups of patients treated
      with ultrasound (US)-guided extracorporeal shock wave (ESW) therapy and with US
      guided injection of platelet-rich plasma (PRP) for chronic lateral epicondylitis
      (LE) with a minimum of 2-year follow-up. METHODS: We retrospectively evaluated 63
      patients treated for chronic LE (31 patients with autologous US-guided PRP
      injection and 32 patients with US-guided focal ESW therapy) from 2009 to 2014.
      All the patients were evaluated by means of Roles-Maudsley (RM) score, quick
      Disabilities of Arm, Shoulder, and Hand (QuickDASH) score, visual analogic scale
      (VAS) and patient-rated tennis elbow evaluation (PRTEE) to retrospectively assess
      the pain relief, level of activity, the self-reported function and subjective
      satisfaction at minimum of 2-year follow-up. RESULTS: Both US-guided autologous
      PRP injection and US-guided focal ESW administration proved effective in chronic
      LE with significant improvement in the QuickDASH, VAS, RM and PRTEE scores ( p <
      0.0001). No adverse effects or complications were recorded in any groups. No
      differences were found in recurrence rate and final results of the QuickDASH,
      VAS, RM and PRTEE scores between the two groups ( p > 0.05). The mean time
      between treatment and symptom resolution was significantly shorter for the PRP
      treatment ( p = 0.0212); furthermore, the mean time to return to the normal
      activities was quicker for PRP group ( p = 0.0119). CONCLUSION: Both PRP
      injection and ESW therapy are feasible and safe options for the treatment of
      chronic LE with low risk of complications and with good long-term follow-up
      results. US-guided PRP injection has quick efficacy when compared with US-guided
      focal ESW therapy.

PMID- 29320965
TI  - Alterations of the Gut Microbiota in Hashimoto's Thyroiditis Patients.
AB  - BACKGROUND: Hashimoto's thyroiditis (HT) is an organ-specific autoimmune disease
      in which both genetic predisposition and environmental factors serve as disease
      triggers. Many studies have indicated that alterations in the gut microbiota are
      important environmental factors in the development of inflammatory and autoimmune
      diseases. A comparative analysis was systematically performed of the gut
      microbiota in HT patients and healthy controls. METHODS: First, a cross-sectional
      study of 28 HT patients and 16 matched healthy controls was conducted. Fecal
      samples were collected, and microbiota were analyzed using 16S ribosomal RNA gene
      sequencing. Second, an independent cohort of 22 HT patients and 11 healthy
      controls was used to evaluate the diagnostic potential of the selected
      biomarkers. RESULTS: Similar levels of bacterial richness and diversity were
      found in the gut microbiota of HT patients and healthy controls (p = 0.11). A
      detailed fecal microbiota Mann-Whitney U-test (Q value <0.05) revealed that the
      abundance levels of Blautia, Roseburia, Ruminococcus_torques_group, Romboutsia,
      Dorea, Fusicatenibacter, and Eubacterium_hallii_group genera were increased in HT
      patients, whereas the abundance levels of Fecalibacterium, Bacteroides,
      Prevotella_9, and Lachnoclostridium genera were decreased. A correlation matrix
      based on the Spearman correlation distance confirmed correlations among seven
      clinical parameters. Additionally, the linear discriminant analysis effect size
      method showed significant differences in 27 genera between the two groups that
      were strongly correlated with clinical parameters. The linear discriminant
      analysis value was used to select the first 10 species from the 27 different
      genera as biomarkers, achieving area under the curve values of 0.91 and 0.88 for
      exploration and validation data, respectively. CONCLUSIONS: Characterization of
      the gut microbiota in HT patients confirmed that HT patients have altered gut
      microbiota and that gut microbiota are correlated with clinical parameters,
      suggesting that microbiome composition data could be used for disease diagnosis.
      Further investigation is required to understand better the role of the gut
      microbiota in the pathogenesis of HT.

PMID- 29320966
TI  - Evaluating barriers to adopting telemedicine worldwide: A systematic review.
AB  - Introduction and objective Studies on telemedicine have shown success in reducing
      the geographical and time obstacles incurred in the receipt of care in
      traditional modalities with the same or greater effectiveness; however, there are
      several barriers that need to be addressed in order for telemedicine technology
      to spread. The aim of this review is to evaluate barriers to adopting
      telemedicine worldwide through the analysis of published work. Methods The
      authors conducted a systematic literature review by extracting the data from the
      Cumulative Index of Nursing and Allied Health Literature (CINAHL) and PubMed
      (MEDLINE) research databases. The reviewers in this study analysed 30 articles
      (nine from CINAHL and 21 from Medline) and identified barriers found in the
      literature. This review followed the checklist from Preferred Reporting Items for
      Systematic Reviews and Meta-Analyses (PRISMA) 2009. The reviewers organized the
      results into one table and five figures that depict the data in different ways,
      organized by: barrier, country-specific barriers, organization-specific barriers,
      patient-specific barriers, and medical-staff and programmer-specific barriers.
      Results The reviewers identified 33 barriers with a frequency of 100 occurrences
      through the 30 articles. The study identified the issues with technically
      challenged staff (11%), followed by resistance to change (8%), cost (8%),
      reimbursement (5%), age of patient (5%), and level of education of patient (5%).
      All other barriers occurred at or less than 4% of the time. Discussion and
      conclusions Telemedicine is not yet ubiquitous, and barriers vary widely. The top
      barriers are technology-specific and could be overcome through training, change
      management techniques, and alternating delivery by telemedicine and personal
      patient-to-provider interaction. The results of this study identify several
      barriers that could be eliminated by focused policy. Future work should evaluate
      policy to identify which one to lever to maximize the results.

PMID- 29320967
TI  - Dolutegravir monotherapy in HIV-1-suppressed patients: A feasible regimen in real
      life.

PMID- 29320968
TI  - HIV in prison: results from a national prison census in Peru.

PMID- 29320969
TI  - Differential expression of TGFbeta isoforms in breast cancer highlights different
      roles during breast cancer progression.
AB  - While TGFbeta plays a critical role in tumor formation and progression, the role
      and contribution of its three different isoforms remain unclear. In this study,
      we aimed at elucidating the prognostic value of the TGFbeta isoforms and assessed
      their expression levels in breast cancer patients at different stages of the
      disease. We found higher levels of TGFbeta1 and TGFbeta3 in cancer patients
      compared to normal tissues, with no significant changes in TGFbeta2 expression.
      Similarly, TGFbeta1 and TGFbeta3, but not TGFbeta2, showed higher expression
      levels in advanced lymph node-positive and metastatic tumors, suggesting
      different roles for the different isoforms in tumor progression and the
      metastatic process, while in the least aggressive molecular subtype (luminal A),
      expression of the three TGFbeta isoforms significantly correlated with expression
      of both TGFbeta receptors, such correlation only occurred between TGFbeta1 and
      TGFbeta3 and the TGFbeta type II receptor (TbetaRII) in the highly aggressive
      basal-like subtype. Interestingly, a distinct and somehow opposite pattern was
      observed in HER-2 tumors, only showing significant association pattern between
      TGFbeta2 and the TGFbeta type I receptor (TbetaRI). Finally, the three TGFbeta
      isoforms showed distinct association patterns with patient outcome depending on
      the different molecular subtype, highlighting context-dependent, differential
      prognostic values.

PMID- 29320970
TI  - Modelling endurance and resumption times for repetitive one-hand pushing.
AB  - This study's objective was to develop models of endurance time (ET), as a
      function of load level (LL), and of resumption time (RT) after loading as a
      function of both LL and loading time (LT) for repeated loadings. Ten male
      participants with experience in construction work each performed 15 different one
      handed repetaed pushing tasks at shoulder height with varied exerted force and
      duration. These data were used to create regression models predicting ET and RT.
      It is concluded that power law relationships are most appropriate to use when
      modelling ET and RT. While the data the equations are based on are limited
      regarding number of participants, gender, postures, magnitude and type of exerted
      force, the paper suggests how this kind of modelling can be used in job design
      and in further research. Practitioner Summary: Adequate muscular recovery during
      work-shifts is important to create sustainable jobs. This paper describes
      mathematical modelling and presents models for endurance times and resumption
      times (an aspect of recovery need), based on data from an empirical study. The
      models can be used to help manage fatigue levels in job design.

PMID- 29320971
TI  - The effect of nutritional intervention on the lipid profile and dietary intake of
      adolescents with juvenile systemic lupus erythematosus: a randomized, controlled
      trial.
AB  - Objective This study sought to evaluate the effects of a nutritional intervention
      on the lipid metabolism biomarkers associated with cardiovascular risk, and their
      variation over time, in juvenile systemic lupus erythematosus (JSLE) patients.
      This study also investigated the relationships between these biomarkers and
      dietary intake, nutritional status, disease variables, and medication used.
      Methods A total of 31 10- to 19-year-old female adolescents with JSLE for at
      least six months were analyzed. The participants were randomly allocated to two
      groups: nutritional intervention or control. The intervention group received
      verbal and printed nutritional instructions once per month over nine months.
      Before and after the intervention, the participants underwent assessments of
      anthropometry; dietary intake; physical activity; socioeconomic status; total
      cholesterol and fractions; triglycerides; apolipoprotein A (Apo A-I);
      apolipoprotein B (Apo B); paraoxonase (PON) activity (a) and amount (q);
      myeloperoxidase (MPO); and small, dense LDL-c (sdLDL) particles. Results After
      nine months, we found significant reductions in the calorie, carbohydrate, total
      fat, saturated fat, and trans fat intakes in the intervention compared with the
      control group over time. The PONa/HDL-c ratio increased by 3.18 U/ml/mg/dl in the
      intervention group and by 0.63 U/ml/mg/dl in the control group ( p = 0.037).
      Unlike the intervention group, the sdLDL levels of the control group worsened
      over time ( p = 0.018). Conclusion The present study detected a reduction in
      calorie and fat intake, which indicates an improvement of HDL-c function and
      possible protection against cardiovascular risk for the intervention group.

PMID- 29320972
TI  - Rituximab use in pediatric lupus anticoagulant hypoprothrombinemia syndrome -
      report of three cases and review of the literature.
AB  - Lupus anticoagulant hypoprothrombinemia syndrome (LA-HPS) is a rare condition
      that may predispose both to thrombosis and bleeding due to positive lupus
      anticoagulant (LA) and factor II (FII) deficiency. It can be seen in association
      with infections or systemic lupus erythematosus (SLE) and may require
      glucocorticoids (GCs) and/or immunosuppressive medications. Pediatric LA-HPS
      cases in the literature and three cases that received only rituximab (RTX) for LA
      HPS (in addition to GCs) at two institutions between January 2010 and June 2017
      were analyzed descriptively. Pediatric LA-HPS cases (<=18 years) with bleeding or
      thrombotic events were included. Information obtained included demographics,
      presenting symptoms, diagnoses, treatments, pre-/post-treatment prothrombin time
      (PT)/partial thromboplastin time (PTT)/LA/FII levels, and outcomes. In addition
      to three LA-HPS cases identified at our institutions, as of June 2017, 37
      articles reported 54 pediatric LA-HPS cases (mean age: 8 years (0.9-17 years);
      female/male: (2:1); viral illness 27 (50%), SLE 20 (37%), and other six (11%)).
      All cases had a positive LA and FII deficiency (range: 0%-40%). All cases
      presented with bleeding diathesis and were treated with various regimens, but
      there was no reported use of RTX. The purpose of this report is to describe the
      novel use of RTX as a steroid-sparing agent in three pediatric SLE cases and to
      systematically review the literature on pediatric cases of LA-HPS.

PMID- 29320973
TI  - Secular trends in the impact factors of SLE publications over a 45-year period-a
      systematic review.
AB  - Objective We assessed publication bias in the field of systemic lupus
      erythematosus (SLE) by conducting a search of randomized, controlled trials
      (RCTs) on SLE therapies that had been published over the past 45 years. Our aim
      was to assess a potential publication bias by determining whether RCTs reporting
      positive results, RCTs with placebo arms, biologics RCTs, and industry-funded
      RCTs are more likely to be published in journals with higher impact factors
      (IFs). Methods We conducted a systematic review of all RCTs registered in PubMed
      between 1 January 1975 and 1 November 2016. Each RCT was classified as having a
      positive result (PR) or a negative result (NR). The IF of each journal was
      determined for the year of publication. Results Our search yielded 233 relevant
      RCTs. There was no significant difference in IFs between studies with NRs and
      those with PRs or between studies that were financially supported by commercial
      companies compared to studies that were not. However, there was a significant
      correlation between sample size and the journal's IF. Conclusions IF scores of
      RCTs in the field of SLE are influenced by sample size and not biased by either a
      tendency to report PRs or by being funded by pharmaceutical companies or any
      other commercial sources.

PMID- 29320974
TI  - Head to head comparison of adverse effects and efficacy between high dose
      deflazacort and high dose prednisolone in systemic lupus erythematosus: a
      prospective cohort study.
AB  - Background Deflazacort (DFZ), an oxazoline derivative of prednisolone (PDN), has
      a dose equivalence of 1.2:1 (mg) to PDN. No study to date has compared adverse
      effects and efficacy of high doses of DFZ as against high-dose PDN in systemic
      lupus erythematosus (SLE). Objectives To compare adverse effects of high dose DFZ
      and PDN in SLE patients, especially in terms of cushingoid features and gain in
      body weight, 3 and 6 months after initiation of these agents. Methods In both the
      steroid arms, the following outcome parameters were assessed at 3 and 6 months:
      (a) cushingoid features by Cushing's Severity Index (CSI) (b) hirsutism by
      modified Ferriman Gallwey score (c) weight gain by difference (Delta, delta) of
      weight (in kilograms). Results Patients on PDN had 1.6 kg (3.2%) and 2 kg (5.1%)
      higher median weight gain as compared to those on DFZ at 3 and 6 months
      respectively (  p = 0.012 and 0.001). PDN caused 10% and 22.2% higher increment
      in median hirsutism scores as compared to DFZ at 3 months and 6 months follow-up,
      respectively (  p = 0.004 and 0.002). PDN caused 100% higher increase in median
      CSI scores than DFZ at 6 months (  p = 0.03). There was no significant difference
      by generalized estimation equation between the groups with respect to changes in
      SLEDAI, renal SLEDAI, anti-dsDNA titres and C3/C4 levels. There were two serious
      infections (requiring hospitalization/intravenous antibiotics) in the PDN group,
      while none in the DFZ group. Conclusion Comparable intake and tapering of high
      dose DFZ and PDN in active SLE revealed 2-fold less weight gain, 2.5-fold less
      hirsutism and 1.5-fold lower cushingoid severity index as well as lower glycaemic
      elevation in the DFZ group as compared to PDN group. Both had similar efficacy.

PMID- 29320975
TI  - Systemic lupus erythematosus with inflammatory bowel disease-ulcerative colitis:
      case report.
AB  - A 30-year-old female presented to the rheumatology outpatient clinic of the
      Internal Medicine Department, Ain Shams University Hospital, Cairo, Egypt,
      complaining of a large right leg ulcer consistent with pyoderma gangrenosum.
      There was history of recurrent attacks of bleeding per rectum of one-year
      duration. During hospitalization she noticed blurring of vision in the left eye
      with diffuse blackish discoloration of the feet and toes, consistent with small
      vessel vasculitis. Colonoscopy with biopsy and histopathology confirmed the
      diagnosis of inflammatory bowel disease-ulcerative colitis (IBD-UC). Meanwhile,
      the patient fulfilled the SLICC classification criteria for systemic lupus
      erythematosus (SLE): recurrent oral ulcers, positive antinuclear antibody
      testing, proteinuria >0.5 gm/24-hour urine, positive test for lupus anticoagulant
      and consumed C3 complement component. Herein we report a rare case of coexistence
      of SLE and IBD-UC.

PMID- 29320976
TI  - The mediational role of helplessness in psychological outcomes in systemic lupus
      erythematosus.
AB  - Objective Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that
      can result in disability and psychological distress. Although pain has been
      associated with depressive symptomatology and stress in SLE, a paucity of
      theoretical models have been used to explain the relationship between pain and
      psychological distress in this population. Thus, the present study examined
      helplessness as a mediator of the relationship between pain and psychological
      distress among patients with SLE. Methods Multiple mediation analysis was used to
      examine the hypothesis that learned helplessness mediates the relationship
      between pain and symptoms of anxiety, depression, and stress in a sample of
      patients with SLE ( N = 136) receiving medical care at Cedars Sinai Medical
      Center. Results The mean score on the Helplessness subscale was 14.5 ( SD = 5.4).
      Helplessness fully mediated the relationship between pain vitality and symptoms
      of anxiety (BCa 95% CI (-0.073, -0.015)), depression (BCa 95% CI (-0.502, 
      0.212)), and stress (BCa 95% CI (-0.063, -0.027)). Conclusion Participants
      reported a high level of perceived inability to control one's disease.
      Helplessness fully mediated the relationship between pain and measures of
      anxiety, depression, and perceived stress among patients with SLE.

PMID- 29320977
TI  - Ibrutinib targets microRNA-21 in multiple myeloma cells by inhibiting NF-kappaB
      and STAT3.
AB  - The oncogenic microRNA-21 contributes to the pathogenesis of multiple myeloma.
      Ibrutinib (also referred to as PCI-32765), an inhibitor of Bruton's tyrosine
      kinase, while its effects on multiple myeloma have not been well described. Here,
      we show that microRNA-21 is an oncogenic marker closely linked with progression
      of multiple myeloma. Moreover, ibrutinib attenuates microRNA-21 expression in
      multiple myeloma cells by inhibiting nuclear factor-kappaB and signal transducer
      and activator of transcription 3 signaling pathways. Taken together, our results
      suggest that ibrutinib is a promising potential treatment for multiple myeloma.
      Further investigation of mechanisms of ibrutinib function in multiple myeloma
      will be necessary to evaluate its use as a novel multiple myeloma treatment.

PMID- 29320978
TI  - Two-Vessel Branched Stent Graft for Severely Angulated Aortic Arch Aneurysm in a
      Jehovah's Witness.
AB  - Aneurysmal disease involving the origins of supra aortic vessels often requires
      complex open and/or endovascular repair that is not only associated with
      significant risk of mortality and morbidity but also often with perioperative
      blood loss requiring transfusion. We report a successful repair of a large
      thoracic aortic aneurysm (TAA) involving the aortic arch with a custom-made
      Bolton Relay 2-vessel branched thoracic aortic endograft in a 42-year-old
      Jehovah's Witness who would otherwise be very unlikely to survive an open repair.
      Branched thoracic aortic endografting offers a potentially safe, minimally
      invasive, and effective alternative for TAA disease involving the supra-aortic
      arteries, especially in patients who are at high risk of open surgery.

PMID- 29320979
TI  - Editorial: Natural Product Inhibitors of Enzymatic Targets in Anticancer Drug
      Discovery - Part I.

PMID- 29320981
TI  - Editorial: Early Recognition of Dementia in Primary Care- Current Issues and
      Concepts.

PMID- 29320982
TI  - Global identification, structural analysis and expression characterization of
      cytochrome P450 monooxygenase superfamily in rice.
AB  - BACKGROUND: The cytochrome P450 monooxygenases (CYP450, CYP, P450) catalyze
      numerous monooxygenation/hydroxylation reactions in biochemical pathways.
      Although CYP superfamily has been systematically studied in a few species, the
      genome-scale research about it in rice has not been done. RESULTS: In this study,
      a total of 355 CYPs encoded by 326 genes were identified in japonica genome. The
      OsCYP genes are classified into 10 clans including 45 families according to
      phylogenetic analysis. More than half of the genes are distributed in 53 tandem
      duplicated gene clusters. Intron-exon structure of OsCYPs exhibits highly
      conserved and specificity within a family, and divergences of duplicate genes in
      gene structure result in non-functionalization, neo-functionalization or sub
      functionalization. Selection pressure analysis showed that rice CYPs are under
      purifying selection. The microarray data analysis shows that some genes are
      tissue-specific expression, such as OsCYP710A5 and OsCYP71X14 in endosperm,
      OsCYP99A3 and OsCYP78A16 in root and OsCYP93G2 and OsCYP97D7 in leaf. Analysis of
      RNA-seq data derived from rice leaf developmental gradient indicates that some
      OsCYPs exhibit zone-specific expression patterns. OsCYP87C2, OsCYP96B5, OsCYP96B8
      and OsCYP84A5 were specifically expressed in leaf base and transitional zone. The
      transcripts of lineages II and IV-1 members were highly abundant in maturing
      zone. Eighty three OsCYPs are differentially expressed in response to drought
      stress, of which OsCYP51G3, OsCYP709C9, OsCYP709C5, OsCYP81A6, OsCYP72A18 and
      OsCYP704A5 are strongly induced and OsCYP78A16, OsCYP89C9 and OsCYP704A5 are down
      regulated significantly, and some of the results were validated by qPCR. And 23
      up-regulated and 17 down-regulated genes are specific to Osbhlh148 mutation under
      drought stress. Compared to those in wild type, the changes in transcript levels
      of several genes are slight in the mutant, such as OsCYP51G3, OsCYP94C2,
      OsCYP709C9 and OsCYP709C5. CONCLUSION: The whole-genomic analysis of rice P450
      superfamily provides a clue to understanding biological function of OsCYPs in
      development regulation and drought stress response, and is helpful to rice
      molecular breeding.

PMID- 29320983
TI  - Independent association of resting energy expenditure with blood pressure:
      confirmation in populations of the African diaspora.
AB  - BACKGROUND: Obesity is a major risk factor for hypertension, however, the
      physiologic mechanisms linking increased adiposity to elevations in blood
      pressure are not well described. An increase in resting energy expenditure (REE)
      is an obligatory consequence of obesity. Previous survey research has
      demonstrated that REE is an independent predictor of blood pressure, and
      eliminates the co-linear association of body mass index. This observation has
      received little attention and there have been no attempts to provide a causal
      explanation. METHODS: At baseline in an international comparative study on
      obesity, 289 participants aged 25-44 were recruited from communities in the US,
      the Seychelles, Ghana and South Africa and had REE measured with indirect
      calorimetry. All participants were thought to be free of major illness. RESULTS:
      In multivariate regression models, both systolic and diastolic blood pressure
      were positively associated with REE (p < 0.01), while body mass index and fat
      mass were negatively correlated with systolic blood pressure (p < 0.01, and p <
      0.05 respectively), but not diastolic blood pressure. CONCLUSIONS: These data
      confirm previous reports and suggest that a common physiologic abnormality links
      REE and blood pressure. Elevated catecholamines, a putative metabolic
      characteristic of obesity, is a possible candidate to explain this association.
      The direct role of excess adipose tissue is open to question.

PMID- 29320984
TI  - Prevalence and antibiotic susceptibility of Uropathogens from cases of urinary
      tract infections (UTI) in Shashemene referral hospital, Ethiopia.
AB  - BACKGROUND: Urinary tract infection (UTI) remains to be one of the most common
      infectious diseases diagnosed in developing countries. And a widespread use of
      antibiotics against uropathogens has led to the emergence of antibiotic resistant
      species. A laboratory based cross-sectional survey was conducted in Shashemene
      referral hospital to determine the prevalence and antibiotic susceptibility of
      uropathogens. METHODS: We have collected 384 clean catch mid-stream urine samples
      from all suspected UTI outpatients using sterile screw capped container. The
      urine samples were cultured and processed for subsequent uropathogens isolation.
      The isolated pure cultures were grown on BiOLOG Universal Growth agar (BUG) and
      identified using GEN III OmniLog(r) Plus ID System identification protocols. The
      identified species were then exposed to selected antibiotics to test for their
      susceptibility. RESULTS: The overall prevalence of urinary tract infection in the
      area was 90.1%. Most frequently isolated uropathogen in our study was Escherichia
      coli (39.3%). While, Staphylococcus species (20.2%), Leuconostoc species (11.4%),
      Raoultella terrigena/Klebsiella spp./ (8.4%), Salmonella typhimurium (6.3%),
      Dermacoccus nishinomiyaensis (6.3%), Citerobacter freundii (5.2%) and
      Issatchenkia orientalis/Candida krusei/ (2.7%) were the other isolates. We find
      that the relationship between uropathogens and some of UTI risk factors was
      statistically significant (P < 0.05). Gentamicin was the most effective drug
      against most of the isolates followed by chloramphenicol and nitrofurantoin. In
      contrast, amoxicillin, vancomycin and cephalexin were the antibiotics to which
      most of the isolates developed resistance. CONCLUSION: Urinary tract infection
      was highly prevalent in the study area and all uropathogens isolated developed a
      resistance against mostly used antibiotics.

PMID- 29320985
TI  - Chlorophyll fluorescence analysis revealed essential roles of FtsH11 protease in
      regulation of the adaptive responses of photosynthetic systems to high
      temperature.
AB  - BACKGROUND: Photosynthetic systems are known to be sensitive to high temperature
      stress. To maintain a relatively "normal" level of photosynthetic activities,
      plants employ a variety of adaptive mechanisms in response to environmental
      temperature fluctuations. Previously, we reported that the chloroplast-targeted
      AtFtsH11 protease played an essential role for Arabidopsis plants to survive at
      high temperatures and to maintain normal photosynthetic efficiency at moderately
      elevated temperature. To investigate the factors contributing to the
      photosynthetic changes in FtsH11 mutant, we performed detailed chlorophyll
      fluorescence analyses of dark-adapted mutant plants and compared them to Col-0 WT
      plants under normal, two moderate high temperatures, and a high light conditions.
      RESULTS: We found that mutation of FtsH11 gene caused significant decreases in
      photosynthetic efficiency of photosystems when environmental temperature raised
      above optimal. Under moderately high temperatures, the FtsH11 mutant showed
      significant 1) decreases in electron transfer rates of photosystem II (PSII) and
      photosystem I (PSI), 2) decreases in photosynthetic capabilities of PSII and PSI,
      3) increases in non-photochemical quenching, and a host of other chlorophyll
      fluorescence parameter changes. We also found that the degrees of these negative
      changes for utilizing the absorbed light energy for photosynthesis in FtsH11
      mutant were correlated with the level and duration of the heat treatments. For
      plants grown under normal temperature and subjected to the high light treatment,
      no significant difference in chlorophyll fluorescence parameters was found
      between the FtsH11 mutant and Col-0 WT plants. CONCLUSIONS: The results of this
      study show that AtFtsH11 is essential for normal photosynthetic function under
      moderately elevated temperatures. The results also suggest that the network
      mediated by AtFtsH11 protease plays critical roles for maintaining the
      thermostability and possibly structural integrity of both photosystems under
      elevated temperatures. Elucidating the underlying mechanisms of FtsH11 protease
      in photosystems may lead to improvement of photosynthetic efficiency under heat
      stress conditions, hence, plant productivity.

PMID- 29320986
TI  - Revealing Alzheimer's disease genes spectrum in the whole-genome by machine
      learning.
AB  - BACKGROUND: Alzheimer's disease (AD) is an important, progressive
      neurodegenerative disease, with a complex genetic architecture. A key goal of
      biomedical research is to seek out disease risk genes, and to elucidate the
      function of these risk genes in the development of disease. For this purpose,
      expanding the AD-associated gene set is necessary. In past research, the
      prediction methods for AD related genes has been limited in their exploration of
      the target genome regions. We here present a genome-wide method for AD candidate
      genes predictions. METHODS: We present a machine learning approach (SVM), based
      upon integrating gene expression data with human brain-specific gene network
      data, to discover the full spectrum of AD genes across the whole genome. RESULTS:
      We classified AD candidate genes with an accuracy and the area under the receiver
      operating characteristic (ROC) curve of 84.56% and 94%. Our approach provides a
      supplement for the spectrum of AD-associated genes extracted from more than
      20,000 genes in a genome wide scale. CONCLUSIONS: In this study, we have
      elucidated the whole-genome spectrum of AD, using a machine learning approach.
      Through this method, we expect for the candidate gene catalogue to provide a more
      comprehensive annotation of AD for researchers.

PMID- 29320987
TI  - Effect of intracoronary agents on the no-reflow phenomenon during primary
      percutaneous coronary intervention in patients with ST-elevation myocardial
      infarction: a network meta-analysis.
AB  - BACKGROUND: Despite the restoration of epicardial flow after primary percutaneous
      coronary intervention (PPCI), myocardial reperfusion remains impaired in a
      significant proportion of patients. We performed a network meta-analysis to
      assess the effect of 7 intracoronary agents (adenosine, anisodamine, diltiazem,
      nicorandil, nitroprusside, urapidil, and verapamil) on the no-reflow phenomenon
      in patients with ST-elevation myocardial infarction (STEMI) undergoing PPCI.
      METHODS: Database searches were conducted to identify randomized controlled
      trials (RCTs) comparing the 7 agents with each other or with standard PPCI.
      Outcome measures included thrombolysis in myocardial infarction flow grade (TFG),
      ST-segment resolution (STR), left ventricular ejection fraction (LVEF), major
      adverse cardiovascular events (MACEs), and adverse events. RESULTS: Forty-one
      RCTs involving 4069 patients were analyzed. The addition of anisodamine to
      standard PPCI for STEMI was associated with improved post-procedural TFG, more
      occurrences of STR, and improvement of LVEF. The cardioprotective effect of
      anisodamine conferred a MACE-free survival benefit. Additionally, nitroprusside
      was regarded as efficient in improving coronary flow and clinical outcomes.
      Compared with standard care, adenosine, nicorandil, and verapamil improved
      coronary flow but had no corresponding benefits regarding cardiac function and
      clinical outcomes. The ranking probability for the 7 treatment drugs showed that
      anisodamine consistently ranked the highest in efficacy outcomes (TFG < 3, STR,
      LVEF, and MACEs). No severe adverse events, such as hypotension and malignant
      arrhythmia, were observed in patients treated with anisodamine. Network meta
      regression analysis showed that age, the time to reperfusion, and study follow-up
      did not affect the treatment effects. CONCLUSIONS: The intracoronary
      administration of anisodamine appears to improve myocardial reperfusion, cardiac
      function, and clinical outcomes in patients with STEMI undergoing PPCI. Given the
      limited quality and quantity of the included studies, more rigorous RCTs are
      needed to verify the role of this inexpensive and well-tolerated regimen.

PMID- 29320988
TI  - Prevalence and key radiographic spinal malalignment parameters that influence the
      risk for gastroesophageal reflux disease in patients treated surgically for adult
      spinal deformity.
AB  - BACKGROUND: Gastroesophageal reflux disease (GERD) is a factor that has a
      significant negative impact on the quality of life (QoL). Vertebral fractures
      and/or spinal malalignment may influence the frequency of GERD. However, the
      epidemiology and pathology of GERD in patients with adult spinal deformity (ASD)
      are still largely unknown. To establish the optimal surgical strategy for GERD in
      patients treated surgically for ASD, we sought to clarify the GERD prevalence,
      determine radiographically which spinal malalignment parameters influence GERD
      risk, and evaluate GERD improvement postoperatively. METHODS: Seventy-one
      consecutive patients with ASD who were treated with thoracolumbar corrective
      surgery and followed up for at least 1 year were enrolled. GERD was diagnosed by
      a gastroenterologist based on proton pump inhibitor medication response and/or an
      FSSG score > 8 points. Full-length lateral radiographs in a standing posture and
      in a supine, fulcrum backward-bending (FBB) position were taken preoperatively
      and 1 year postoperatively, and radiographic parameters were obtained.
      Correlations between radiographic parameters and FSSG scores were determined by
      Pearson's correlation coefficient. Multivariate logistic regression analyses were
      performed to evaluate the odds ratio (OR) with a 95% confidence interval (95% CI)
      for potential risk factors for GERD. RESULTS: Patients were classified into two
      groups based on GERD symptoms, with 37 (52%) in the GERD+ group. Thoracolumbar
      kyphosis (TLK) in the FBB position was significantly more common in the GERD+
      versus the GERD- group. Multivariate logistic regression analysis showed that
      lumbar lordosis (LL) and TLK curve in the FBB position significantly influenced
      the presence of GERD. Other factors showed no association with GERD. Significant
      improvements in FSSG scores were noted 1 year postoperatively. However, 20
      (28.2%) patients still had GERD symptoms. The postoperative TLK curve was highly
      significantly correlated with FSSG scores 1 year postsurgery. CONCLUSIONS: Of the
      71 patients treated surgically for ASD, 37 (52%) had a high frequency of GERD
      symptoms. An inflexible thoracolumbar curve with increased TLK in the FBB
      position was significantly associated with GERD symptoms. Despite significant
      improvements in FSSG scores postoperatively, insufficient correction of TLK might
      be a risk factor for persistent GERD symptoms.

PMID- 29320989
TI  - Expression of Vimentin in hair follicle growth cycle of inner Mongolian Cashmere
      goats.
AB  - BACKGROUND: The growth of Inner Mongolian Cashmere goat skin hair follicle
      exhibits a periodic growth pattern. The hair growth cycle is distinguished as
      telogen, anagen, and catagen stages. The role of vimentin in the growth process
      of hair follicles is evident. To elucidate the mechanism underlying the vimentin
      activity in the growth cycle of hair follicles, transcriptome sequencing and
      liquid chromatography-tandem mass spectrometry were used to obtain the nucleic
      acid and amino acid sequences of VIIM gene and vimentin. The amino acid and
      nucleic acid sequences were analyzed by comparison. Real-time quantitative PCR,
      Western blot, and immunohistochemistry analyzed the expression level and sites of
      vimentin in the three growth stages of the Inner Mongolia Cashmere goat skin
      samples. RESULTS: VIM gene cDNA, obtained by transcriptome sequencing, was
      aligned against that of the Capra hircus VIM gene. The amino acid sequence of
      vimentin revealed a high similarity rate across other species. The expressions of
      both VIM gene and vimentin were highest during the growth period and lowest in
      the rest period. Furthermore, vimentin was primarily expressed in the outer root
      sheath of the hair follicle as assessed by staining. CONCLUSIONS: The sequences
      of the gene and protein are similar to that of other species and identical to
      Capra hircus. However, the expression of VIM and vimentin was proportional to
      that of the growth of hair follicles. And vimentin expressed only in the outer
      root sheath of hair follicles. Thus, vimentin was speculated to participate in
      the regulation of the hair follicle growth cycle by affecting the outer root
      sheath.

PMID- 29320990
TI  - Correlation between polymorphisms in toll-like receptor genes and the activity of
      hepatitis B virus among treatment-naive patients: a case-control study in a Han
      Chinese population.
AB  - BACKGROUND: Because of the high prevalence and absence of cure for infection,
      chronic hepatitis B virus (HBV) infection has been acknowledged as a pressing
      public health issue. Toll-like receptors (TLRs) activate the human innate immune
      system and the polymorphisms in TLRs may alter their function. The present study
      aimed to investigate the association between TLR polymorphisms and disease
      progression of chronic HBV infection. METHODS: During the study period, 211
      treatment-naive patients with chronic HBV infection were recruited, and blood
      samples were collected from each individual. Matrix-assisted laser
      desorption/ionization time of flight mass spectrometry was employed to genotype
      the selected TLR polymorphisms after human genome extraction. In addition, HbsAg,
      TNF-alpha, and IL-6 levels were quantified using enzyme linked immunosorbent
      assay (ELISA). Statistical analyses were conducted to investigate the association
      between TLR polymorphisms and hepatitis activity, liver function parameters,
      HbsAg level, and cytokine level. RESULTS: We did not observe any mutations in
      rs4986790, rs4986791, and rs5743708 among all study subjects. A logistic
      regression revealed that mutations in rs3804099 and rs4696480 were associated
      with milder hepatitis activity. Consistent with the logistic regression, improved
      liver function parameters and reduced level of both HbsAg and cytokines were also
      correlated with the mutant carriers of rs3804099 and rs4696480. CONCLUSIONS: TLR
      mutations were significantly associated with milder hepatitis activity among
      patients with chronic HBV infection. Therefore, we conclude that the activation
      of TLR pathways may further intensify the inflammation of hepatocytes, and leads
      to progression of disease.

PMID- 29320991
TI  - An oncogenic mutant of RHEB, RHEB Y35N, exhibits an altered interaction with BRAF
      resulting in cancer transformation.
AB  - BACKGROUND: RHEB is a unique member of the RAS superfamily of small GTPases
      expressed in all tissues and conserved from yeast to humans. Early studies on
      RHEB indicated a possible RHEB-RAF interaction, but this has not been fully
      explored. Recent work on cancer genome databases has revealed a reoccurring
      mutation in RHEB at the Tyr35 position, and a recent study points to the
      oncogenic potential of this mutant that involves activation of RAF/MEK/ERK
      signaling. These developments prompted us to reassess the significance of RHEB
      effect on RAF, and to compare mutant and wild type RHEB. METHODS: To study RHEB
      RAF interaction, and the effect of the Y35N mutation on this interaction, we used
      transfection, immunoprecipitation, and Western blotting techniques. We generated
      cell lines stably expressing RHEB WT, RHEB Y35N, and KRAS G12V, and monitored
      cellular transforming properties through cell proliferation, anchorage
      independent growth, cell cycle analysis, and foci formation assays. RESULTS: We
      observe a strong interaction between RHEB and BRAF, but not with CRAF. This
      interaction is dependent on an intact RHEB effector domain and RHEB-GTP loading
      status. RHEB overexpression decreases RAF activation of the RAF/MEK/ERK pathway
      and RHEB knockdown results in an increase in RAF/MEK/ERK activation. RHEB Y35N
      mutation has decreased interaction with BRAF, and RHEB Y35N cells exhibit greater
      BRAF/CRAF heterodimerization resulting in increased RAF/MEK/ERK signaling. This
      leads to cancer transformation of RHEB Y35N stably expressing cell lines, similar
      to KRAS G12 V expressing cell lines. CONCLUSIONS: RHEB interaction with BRAF is
      crucial for inhibiting RAF/MEK/ERK signaling. The RHEB Y35N mutant sustains
      RAF/MEK/ERK signaling due to a decreased interaction with BRAF, leading to
      increased BRAF/CRAF heterodimerization. RHEB Y35N expressing cells undergo cancer
      transformation due to decreased interaction between RHEB and BRAF resulting in
      overactive RAF/MEK/ERK signaling. Taken together with the previously established
      function of RHEB to activate mTORC1 signaling, it appears that RHEB performs a
      dual function; one is to suppress the RAF/MEK/ERK signaling and the other is to
      activate mTORC1 signaling.

PMID- 29320992
TI  - Caesarean delivery-related blood transfusion: correlates in a tertiary hospital
      in Southwest Nigeria.
AB  - BACKGROUND: Caesarean delivery carries a risk of major intra-operative blood loss
      and its performance is often delayed by non-availability of blood and blood
      products. Unnecessary cross-matching and reservation of blood lead to apparent
      scarcity in centres with limited supply. This study set out to identify the risk
      factors for blood transfusion in women who underwent caesarean delivery at a
      tertiary obstetric unit with a view to ensuring efficient blood utilization.
      METHODS: A prospective cohort analysis of 906 women who had caesarean deliveries
      at the Lagos State University Teaching Hospital, Nigeria between January and
      December, 2011. A comparison was made between 188 women who underwent blood
      transfusion and 718 who did not. Data were obtained on a daily basis by
      investigators from patients, clinical notes and referral letters using structured
      pre-tested data collecting form. Socio-demographic characteristics; antenatal,
      perioperative and intraoperative details; blood loss; transfusion; and puerperal
      observations were recorded. EPI-Info statistical software version 3.5.3 was used
      for multivariable analysis to determine independent risk factors for blood
      transfusion. RESULTS: Of the 2134 deliveries during the study period, 906 (42.5%)
      had caesarean deliveries and of which 188 (20.8%) were transfused. The modal unit
      of blood transfused was 3 pints (41.3%). The most common indication for caesarean
      section was cephalo-pelvic disproportion (25.7%).The independent risk factors for
      blood transfusion at caesarean section were second stage Caesarean Section (aOR =
      76.14, 95% CI = 1.25-4622.06, p = 0.04), placenta previa (aOR = 32.57, 95% CI =
      2.22-476.26, p = 0.01), placental abruption (aOR = 25.35, 95% CI = 3.06-211.02, p
      < 0.001), pre-operative anaemia (aOR = 12.15, 95% = CI 4.02-36.71, p < 0.001),
      prolonged operation time (aOR = 10.72 95% CI = 1.37-36.02, p < 0.001), co
      morbidities like previous uterine scar (aOR = 7.02, 95% CI = 1.37-36.02, p =
      0.02) and hypertensive disorders in pregnancy (aOR = 5.19, 95% CI = 1.84-14.68, p
      < 0.001). Obesity reduced the risk for blood transfusion (aOR = 0.24, 95% CI =
      0.09-0.61, p = 0.0024). CONCLUSION: The overall risk of blood transfusion in
      cesarean delivery is high. Paturients with the second stage Caesarean section,
      placenta previa, abruptio placentae and preoperative maternal anaemia have an
      increased risk of blood transfusion. Hence, adequate peri-operative preparations
      for blood transfusion are essential in these situations. Optimizing maternal
      hemoglobin concentration during antenatal period may reduce the incidence of
      caesarean-associated blood transfusion.

PMID- 29320993
TI  - Distribution of glomerular diseases in Taiwan: preliminary report of National
      Renal Biopsy Registry-publication on behalf of Taiwan Society of Nephrology.
AB  - BACKGROUND: Despite the development of biomarkers and noninvasive imaging tools,
      biopsy remains the only method for correctly diagnosing patients with unexplained
      hematuria, proteinuria and renal failure. Renal biopsy has been performed for
      several decades in Taiwan; however, a national data registry is still lacking
      until 2013. METHODS: The Renal Biopsy Registry Committee was established within
      the Taiwan Society of Nephrology in January 2013. A biopsy registry format,
      including basic demographic data, baseline clinical features, laboratory data,
      and clinical and pathological diagnosis was developed. Approval from the local
      institutional review board was obtained in each participating medical center.
      RESULTS: From January 2014 to September 2016, 1445 renal biopsies were identified
      from 17 medical centers. 53.8% cases were reported in men. After excluding renal
      transplantation, renal biopsies were commonly performed in patients with primary
      glomerulonephritis (48.1%), secondary glomerulonephritis (36.2%), followed by
      tubulointerstitial diseases (12.3%) and vascular nephropathy (3.4%). Among
      primary glomerulonephritis, IgA nephropathy (26.0%), focal segmental
      glomerulosclerosis (21.6%), and membranous nephropathy (20.6%) were most
      frequently diagnosed. Diabetic nephropathy (22.4%) and lupus nephritis (21.8%)
      were the most common among secondary glomerulonephritis. Patients with minimal
      change disease and membranous nephropathy had heavier proteinuria than those with
      focal segmental glomerulosclerosis and IgA nephropathy (P < 0.001). Patients with
      minimal change disease had higher serum IgM and IgE levels. The most common cause
      of nephrotic syndrome in primary glomerular disease was membranous nephropathy
      (28.8%), followed by minimal change disease (28.2%). IgA nephropathy was the
      leading cause of chronic nephritic syndrome, acute nephritic syndrome, and
      persistent hematuria. The incidence of primary glomerulonephritis was
      approximately 2.19 in 100,000/year. CONCLUSIONS: This is the first report of the
      National Renal Biopsy Registry in Taiwan. IgA nephropathy is the most common
      primary glomerulonephritis, while membranous nephropathy is the most common cause
      of nephrotic syndrome. Primary glomerulonephritis distribution in Taiwan is
      slightly different from that in other Asian countries.

PMID- 29320994
TI  - Promoting sustainability in quality improvement: an evaluation of a web-based
      continuing education program in blood pressure measurement.
AB  - BACKGROUND: The accuracy of blood pressure measurement is variable in office
      based settings. Even when staff training programs are effective, knowledge and
      skills decay over time, supporting the need for ongoing staff training. We
      evaluated whether a web-based continuing education program in blood pressure
      measurement reinforced knowledge and skills among clinical staff and promoted
      sustainability of an existing quality improvement program. METHODS: Medical
      assistants and nurses at six primary care clinics within a health system enrolled
      in a 30-min online educational program designed to refresh their knowledge of
      blood pressure measurement. A 20-question pre- and post-intervention survey
      addressed learners' knowledge and attitudes. Direct observation of blood pressure
      measurement technique before and after the intervention was performed.
      Differences in responses to pre- and post-module knowledge and attitudes
      questions and in observation data were analyzed using chi-square tests and simple
      logistic regression. RESULTS: All 88 clinical staff members participated in the
      program and completed the evaluation survey. Participants answered 80.6% of
      questions correctly before the module and 93.4% afterwards (p < 0.01). Scores
      improved significantly among staff from all job types. Licensed practical nurses
      and staff who had been in their current job at least a year were more likely to
      answer questions correctly than registered nurses and those in their current job
      less than a year. Attitudes toward correct blood pressure measurement were high
      at baseline and did not improve significantly. Prior to the intervention, staff
      adhered to 9 of 18 elements of the recommended technique during at least 90% of
      observations. Following the program, staff was more likely to explain the
      protocol, provide a rest period, measure an average blood pressure, and record
      the average blood pressure, but less likely to measure blood pressure with the
      arm at heart level and use the right arm. CONCLUSIONS: We designed, implemented,
      and evaluated a web-based educational program to improve knowledge, skills, and
      attitudes in blood pressure measurement and use of an automated device among
      nurses and medical assistants in ambulatory care. The program reinforced
      knowledge related to recommended blood pressure measurement technique. TRIAL
      REGISTRATION: Retrospectively registered with ClincalTrials.gov on March 22,
      2012; registration number NCT01566864 .

PMID- 29320995
TI  - Metformin, Asian ethnicity and risk of prostate cancer in type 2 diabetes: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Metformin is associated with a reduced risk of some cancers but its
      effect on prostate cancer is unclear. Some studies suggest only Asians derive
      this benefit. Therefore, we undertook a systematic review with particular
      attention to ethnicity. METHODS: Medline, Embase, Scopus, Web of Science, and EBM
      Reviews were searched from inception to 2015. Two reviewers identified and
      abstracted articles. Studies were pooled using random effects model and
      stratified by Western- vs Asian-based populations. RESULTS: We identified 482
      studies; 26 underwent full review. Of Western-based studies (n = 23), two were
      randomized trials and 21 were observational studies. All Asian-based studies (n =
      3) were observational. There were 1,572,307 patients, 1,171,643 Western vs
      400,664 Asian. Across all studies there was no association between metformin and
      prostate cancer (RR: 1.01, 95%CI: 0.86-1.18, I2: 97%), with similar findings in
      Western-based trials (RR: 1.38, 95%CI: 0.72-2.64 I2: 15%) and observational
      studies (RR: 1.03 95%CI: 0.94-1.13, I2: 88%). Asian-based studies suggested a non
      significant reduction (RR: 0.75, 95%CI: 0.42-1.34, I2: 90%), although these
      results were highly influenced by one study of almost 400,000 patients
      (propensity-adjusted RR: 0.47 95%CI 0.45-0.49). Removing this influential study
      yielded an estimate more congruent with Western-based studies (RR: 0.98
      95%CI:0.71-1.36, I2: 0%). CONCLUSION: There is likely no association between
      metformin and risk of prostate cancer, in either Western-based or Asian-based
      populations after removing a highly influential Asian-based study.

PMID- 29320996
TI  - Healthy apple program to support child care centers to alter nutrition and
      physical activity practices and improve child weight: a cluster randomized trial.
AB  - BACKGROUND: North Carolina Nutrition and Physical Activity Self-Assessment for
      Child Care (NAP SACC) resources improve child body mass index (BMI) when the
      resources are introduced by nurses to child care providers, and offered with
      workshops and incentives. In San Francisco, public health and child care agencies
      partnered to adapt NAP SACC resources into an annual "Healthy Apple" quality
      improvement program (HAP). METHODS: This cluster randomized controlled trial
      pilot-tested integration of the HAP with bi-annual public health screenings by
      nurses. All child care centers that participated in Child Care Health Program
      (CCHP) screenings in San Francisco in 2011-2012 were offered routine services
      plus HAP in 2012-2013 (CCHP + HAP, n = 19) or routine services with delayed HAP
      in 2014-2015 (CCHP + HAP Delayed, n = 24). Intention-to-treat analyses (robust SE
      or mixed models) used 4 years of screening data from 12 to 17 CCHP + HAP and 17
      to 20 CCHP + HAP Delayed centers, regarding 791 to 945 children ages 2 to 5y,
      annually. Year-specific, child level models tested if children in CCHP + HAP
      centers had greater relative odds of exposure to 3 index best practices and
      smaller Autumn-to-Spring changes in BMI percentile and z-score than children in
      CCHP + HAP Delayed centers, controlling for age, sex, and Autumn status. Multi
      year, child care center level models tested if HAP support modified year-to-year
      changes (2013-2014 and 2014-2015 vs 2011-2012) in child care center annual mean
      Autumn-to-Spring BMI changes. RESULTS: In 2011-2012, the CCHP + HAP and CCHP +
      HAP Delayed centers had similar index practices (<15% of children were exposed to
      a physical activity curriculum, staff joining in active play, and drinking water
      pitchers) and annual BMI changes. In 2013-2014: 60% of children in CCHP + HAP
      centers were exposed to the 3 index practices vs 19% in CCHP + HAP Delayed
      centers; Mean (SE) child BMI percentile (-2.6 (0.9), p = 0.003) and z-score (
      0.08 (0.03), p = 0.007) decreased more in CCHP + HAP vs CCHP + HAP Delayed
      centers. In 2014-2015, after all centers were offered HAP, the index practices
      and BMI changes were improved for all centers vs 2011-2012. CONCLUSIONS:
      Integration of the HAP with existing public health nursing services was
      associated with significantly more children exposed to best practices and
      improvement in child BMI change. The results warrant continued integration of HAP
      into local public health infrastructure. TRIAL REGISTRATION: ISRCTN18857356
      (24/04/2015) Retrospectively registered.

PMID- 29320997
TI  - Investigating the associations between productive housework activities, sleep
      hours and self-reported health among elderly men and women in western
      industrialised countries.
AB  - BACKGROUND: After retirement, elderly men and women allocate more time to
      housework activities, compared to working-age adults. Nonetheless, sleep
      constitutes the lengthiest time use activity among the elderly, but there has not
      been any study on the associations between time spent on housework activities,
      sleep duration and self-reported health among the older population. This study
      not only examined individual associations between self-reported health and both
      housework activities and sleep duration, but it also explored self-reported
      health by the interaction effect between housework activities and sleep duration
      separately for men and women. METHODS: Pooled data from the Multinational Time
      Use Study (MTUS) on 15,333 men and 20,907 women from Germany, Italy, Spain, UK,
      France, the Netherlands and the US were analysed. Multiple binary logistic
      regression models were used to examine the associations between three broad
      categories of housework activities ((1) cooking, cleaning and shopping, (2)
      gardening and maintenance; (3) childcare) and health. We further investigated the
      extent to which total housework hours and sleep duration were associated with
      self-reported health for men and women separately. RESULTS: We found a positive
      association between time devoted to housework activities, total housework and
      health status among elderly men and women. Compared to those who spent 1 to 3 h
      on total productive housework, elderly people who spent >3 to 6 h/day had higher
      odds of reporting good health (OR = 1.25; 95% CI = 1.14-1.37 among men and OR =
      1.10; 95% CI = 1.01-1.20 among women). Both short (<7 h) and long (>8 h) sleep
      duration were negatively associated with health for both genders. However, the
      interactive associations between total productive housework, sleep duration, and
      self-reported health varied among men and women. Among women, long hours of
      housework combined with either short or long sleep was negatively associated with
      health. CONCLUSIONS: Although time allocation to housework activities may be
      beneficial to the health among both genders, elderly women have higher odds of
      reporting poor health when more time is devoted total housework combined with
      either short or long sleep duration.

PMID- 29320998
TI  - The perceptions and experiences of women who achieved and did not achieve a
      waterbirth.
AB  - BACKGROUND: There is a gap in knowledge and understanding relating to the
      experiences of women exposed to the opportunity of waterbirth. Our aim was to
      explore the perceptions and experiences of women who achieved or did not achieve
      their planned waterbirth. METHODS: An exploratory design using critical incident
      techniques was conducted between December 2015 and July 2016, in the birth centre
      of the tertiary public maternity hospital in Western Australia. Women were
      telephoned 6 weeks post birth. Demographic data included: age; education; parity;
      and previous birth mode. Women were also asked the following: what made you
      choose to plan a waterbirth?; what do you think contributed to you having (or not
      having) a waterbirth?; and which three words would you use to describe your birth
      experience? Frequency distributions and univariate comparisons were employed for
      quantitative data. Thematic analysis was undertaken to extract common themes from
      the interviews. RESULTS: A total of 31% (93 of 296) of women achieved a
      waterbirth and 69% (203 of 296) did not. Multiparous women were more likely to
      achieve a waterbirth (57% vs 32%; p < 0.001). Women who achieved a waterbirth
      were less likely to have planned a waterbirth for pain relief (38% vs 52%; p =
      0.24). The primary reasons women gave for planning a waterbirth were: pain
      relief; they liked the idea; it was associated with a natural birth; it provided
      a relaxing environment; and it was recommended. Two fifths (40%) of women who
      achieved a waterbirth suggested support was the primary reason they achieved
      their waterbirth, with the midwife named as the primary support person by 34 of
      37 women. Most (66%) women who did not achieve a waterbirth perceived this was
      because they experienced an obstetric complication. The words women used to
      describe their birth were coded as: affirming; distressing; enduring; natural;
      quick; empowering; and long. CONCLUSIONS: Immersion in water for birth
      facilitates a shift of focus from high risk obstetric-led care to low risk
      midwifery-led care. It also facilitates evidence based, respectful midwifery care
      which in turn optimises the potential for women to view their birthing experience
      through a positive lens.

PMID- 29321000
TI  - Care quality following intrauterine death in Spanish hospitals: results from an
      online survey.
AB  - BACKGROUND: The objective of the study was to evaluate practices in Spanish
      hospitals after intrauterine death in terms of medical/ technical care and
      bereavement support care. METHODS: A cross-sectional descriptive study using an
      online self-completion questionnaire. The population was defined as women who had
      experienced an intrauterine fetal death between sixteen weeks and birth, either
      through spontaneous late miscarriage/stillbirth or termination of pregnancy for
      medical reasons. Respondents were recruited through an online advertisement on a
      stillbirth charity website and social media. The analysis used Pearson's chi
      squared (p <= 0.05) test of independence to cross-analyse for associations
      between objective measures of care quality and independent variables. RESULTS:
      Responses from 796 women were analysed. Half of the women (52.9%) had postmortem
      contact with their baby. 30.4% left the hospital with a least one linking object
      or a photograph. In 35.8% of cases parents weren't given any option to recover
      the body/remains. 22.9% of births >=26 weeks gestation were by caesarean, with a
      significant (p < 0.001) difference between public hospitals (16.8%) and private
      hospitals (41.5%). 29.3% of respondents were not accompanied during the delivery.
      48.0% of respondents recalled being administered sedatives at least once during
      the hospital stay. The autopsy rate in stillbirth cases (>= 20 weeks) was 70.5%
      and 44.4% in cases of termination of pregnancy (all gestational ages). Consistent
      significant (p < 0.05) differences in care practices were found based on
      gestational age and type of hospital (public or private), but not to other
      variables related to socio-demographics, pregnancy history or details of the
      loss/death. Intrauterine deaths at earlier gestational ages received poorer
      quality care. CONCLUSIONS: Supportive healthcare following intrauterine death is
      important to women's experiences in the hospital and beneficial to the grief
      process. Many care practices that are standard in other high-income countries are
      not routine in Spanish hospitals. Providing such care is a relatively new
      phenomenon in the Spanish health system, the results provide a quality benchmark
      and identify a number of areas where hospitals could make improvements to care
      practices that should have important psychosocial benefits for women and their
      families.

PMID- 29320999
TI  - Gender differences in mental health problems among adolescents and the role of
      social support: results from the Belgian health interview surveys 2008 and 2013.
AB  - BACKGROUND: To investigate how social support relates to mental health problems
      for Belgian late adolescents and young adults 15-25 years of age. Additionally,
      we examine changes in mental health problems between 2008 and 2013 and
      investigate gender differences. METHODS: Multivariate analysis of variance was
      used to investigate (1) psychological distress, (2) anxiety and (3) depression
      among 713 boys and 720 girls taken from two successive waves (2008 and 2013) of a
      representative sample of the Belgian population (Belgian Health Interview
      survey). Psychological distress was measured by the General Health Questionnaire,
      anxiety and depression by the Symptom Check-List-90-Revised. RESULTS: Gender
      differences were found for psychological distress, anxiety and depression with
      girls reporting significantly higher scores than boys. Multivariate analysis of
      variance (MANOVA) revealed that adolescents who are dissatisfied with their
      social contacts and experience poor social support reported more psychological
      distress, anxiety and depression. In addition, young adult boys (20-25 years of
      age) were more likely to experience psychological distress when compared to late
      adolescent boys (15-19 years of age). Finally, the prevalence of anxiety and
      depression increased substantially between 2008 and 2013 for girls and to a
      lesser extent for boys. CONCLUSIONS: Especially girls and young people with poor
      social support experience mental health problems more frequently than boys and
      those with strong social support. Improving social support among young people may
      serve as a protective buffer to mental health problems.

PMID- 29321001
TI  - Dengue virus infection-enhancement activity in neutralizing antibodies of healthy
      adults before dengue season as determined by using FcgammaR-expressing cells.
AB  - BACKGROUND: Antibodies are critical responses to protect the host from dengue
      virus(DENV) infection. Antibodies target DENV by two pathologic mechanisms: virus
      neutralization and infection enhancement. In dengue patients, the absence of
      neutralizing activity in the presence of FcgammaR implies that infection
      enhancing activity hampers the neutralizing activity of antibodies, which could
      potentially lead to symptomatic presentations and severe clinical outcomes.
      METHODS: A total of 100 pair serum samples from adult healthy volunteers were
      obtained during the dengue season in Ha Noi in 2015 for evaluation of
      neutralizing and infection-enhancing activity. Additionally, 20 serum samples
      from acute secondary DENV infection patients were also used as the patient group
      in this study. PRNT was performed on BHK cells and FcgammaR-expressing BHK cell
      lines for all serum samples. RESULTS: Out of 100 residents, positive neutralizing
      antibodies (N.A) were found in 44.23 and 76.92% for DENV-1; 38.46 and 75% for
      DENV-2; 19.23 and 15.38% for DENV-3; and 1.92 and 9.62% for DENV-4 for pre and
      post-dengue season respectively. The percentage of post-exposure residents having
      positive responses against single, two, or more than three DENV serotypes were
      38.46, 44.23 and 15.38%, respectively. A total of 34 residents were DENV
      seropositive before the dengue season and these individuals demonstrated further
      elevation of IgG antibodies after the dengue season. At the end of the season, 18
      residents were confirmed to be new asymptomatic DENV infection cases. In both
      groups, N.A titers determined on BHK cells were higher than that on FcgammaR
      expressing BHK cells. In heterotypic N.A responses, N.A titers to the infecting
      serotype from the samples obtained from pre-exposure group were significantly
      higher than those of the patient group. However, fold enhancement to the
      infecting serotypes from the samples in the pre-exposure group was substantially
      lower as compared to that of the patient group. CONCLUSION: Before and after the
      dengue season, serum samples from healthy volunteers demonstrated high levels of
      neutralizing antibodies and low or absence of infection-enhancement activity. The
      results suggest that while infection-enhancement activity hampers neutralizing
      activity of antibodies, high levels of DENV neutralizing antibodies set a
      critical threshold in facilitating the prevention of disease progression.

PMID- 29321002
TI  - Comparison of nuisance parameters in pediatric versus adult randomized trials: a
      meta-epidemiologic empirical evaluation.
AB  - BACKGROUND: We wished to compare the nuisance parameters of pediatric vs. adult
      randomized-trials (RCTs) and determine if the latter can be used in sample size
      computations of the former. METHODS: In this meta-epidemiologic empirical
      evaluation we examined meta-analyses from the Cochrane Database of Systematic
      Reviews, with at least one pediatric-RCT and at least one adult-RCT. Within each
      meta-analysis of binary efficacy-outcomes, we calculated the pooled-control-group
      event-rate (CER) across separately all pediatric and adult-trials, using random
      effect models and subsequently calculated the control-group event-rate risk-ratio
      (CER-RR) of the pooled-pediatric-CERs vs. adult-CERs. Within each meta-analysis
      with continuous outcomes we calculated the pooled-control-group effect standard
      deviation (CE-SD) across separately all pediatric and adult-trials and
      subsequently calculated the CE-SD-ratio of the pooled-pediatric-CE-SDs vs. adult
      CE-SDs. We then calculated across all meta-analyses the pooled-CER-RRs and pooled
      CE-SD-ratios (primary endpoints) and the pooled-magnitude of effect-sizes of CER
      RRs and CE-SD-ratios using REMs. A ratio < 1 indicates that pediatric trials have
      smaller nuisance parameters than adult trials. RESULTS: We analyzed 208 meta
      analyses (135 for binary-outcomes, 73 for continuous-outcomes). For binary
      outcomes, pediatric-RCTs had on average 10% smaller CERs than adult-RCTs (summary
      CE-RR: 0.90; 95% CI: 0.83, 0.98). For mortality outcomes the summary-CE-RR was
      0.48 (95% CIs: 0.31, 0.74). For continuous outcomes, pediatric-RCTs had on
      average 26% smaller CE-SDs than adult-RCTs (summary-CE-SD-ratio: 0.74).
      CONCLUSIONS: Clinically relevant differences in nuisance parameters between
      pediatric and adult trials were detected. These differences have implications for
      design of future studies. Extrapolation of nuisance parameters for sample-sizes
      calculations from adult-trials to pediatric-trials should be cautiously done.

PMID- 29321004
TI  - RCC2 over-expression in tumor cells alters apoptosis and drug sensitivity by
      regulating Rac1 activation.
AB  - BACKGROUND: Small GTP binding protein Rac1 is a component of NADPH oxidases and
      is essential for superoxide-induced cell death. Rac1 is activated by guanine
      nucleotide exchange factors (GEFs), and this activation can be blocked by
      regulator of chromosome condensation 2 (RCC2), which binds the switch regions of
      Rac1 to prevent access from GEFs. METHODS: Three cancer cell lines with up- or
      down-regulation of RCC2 were used to evaluate cell proliferation, apoptosis, Rac1
      signaling and sensitivity to a group of nine chemotherapeutic drugs. RCC2
      expression in lung cancer and ovarian cancer were studied using immunochemistry
      stain of tumor tissue arrays. RESULTS: Forced RCC2 expression in tumor cells
      blocked spontaneous- or Staurosporine (STS)-induced apoptosis. In contrast, RCC2
      knock down in these cells resulted in increased apoptosis to STS treatment. The
      protective activity of RCC2 on apoptosis was revoked by a constitutively
      activated Rac1, confirming a role of RCC2 in apoptosis by regulating Rac1. In an
      immunohistochemistry evaluation of tissue microarray, RCC2 was over-expressed in
      88.3% of primary lung cancer and 65.2% of ovarian cancer as compared to non
      neoplastic lung and ovarian tissues, respectively. Because chemotherapeutic drugs
      can kill tumor cells by activating Rac1/JNK pathway, we suspect that tumors with
      RCC2 overexpression would be more resistant to these drugs. Tumor cells with
      forced RCC2 expression indeed had significant difference in drug sensitivity
      compared to parental cells using a panel of common chemotherapeutic drugs.
      CONCLUSIONS: RCC2 regulates apoptosis by blocking Rac1 signaling. RCC2 expression
      in tumor can be a useful marker for predicting chemotherapeutic response.

PMID- 29321003
TI  - A prototypical non-malignant epithelial model to study genome dynamics and
      concurrently monitor micro-RNAs and proteins in situ during oncogene-induced
      senescence.
AB  - BACKGROUND: Senescence is a fundamental biological process implicated in various
      pathologies, including cancer. Regarding carcinogenesis, senescence signifies, at
      least in its initial phases, an anti-tumor response that needs to be circumvented
      for cancer to progress. Micro-RNAs, a subclass of regulatory, non-coding RNAs,
      participate in senescence regulation. At the subcellular level micro-RNAs,
      similar to proteins, have been shown to traffic between organelles influencing
      cellular behavior. The differential function of micro-RNAs relative to their
      subcellular localization and their role in senescence biology raises concurrent
      in situ analysis of coding and non-coding gene products in senescent cells as a
      necessity. However, technical challenges have rendered in situ co-detection
      unfeasible until now. METHODS: In the present report we describe a methodology
      that bypasses these technical limitations achieving for the first time
      simultaneous detection of both a micro-RNA and a protein in the biological
      context of cellular senescence, utilizing the new commercially available
      SenTraGorTM compound. The method was applied in a prototypical human non
      malignant epithelial model of oncogene-induced senescence that we generated for
      the purposes of the study. For the characterization of this novel system, we
      applied a wide range of cellular and molecular techniques, as well as high
      throughput analysis of the transcriptome and micro-RNAs. RESULTS: This
      experimental setting has three advantages that are presented and discussed: i) it
      covers a "gap" in the molecular carcinogenesis field, as almost all corresponding
      in vitro models are fibroblast-based, even though the majority of neoplasms have
      epithelial origin, ii) it recapitulates the precancerous and cancerous phases of
      epithelial tumorigenesis within a short time frame under the light of natural
      selection and iii) it uses as an oncogenic signal, the replication licensing
      factor CDC6, implicated in both DNA replication and transcription when over
      expressed, a characteristic that can be exploited to monitor RNA dynamics.
      CONCLUSIONS: Consequently, we demonstrate that our model is optimal for studying
      the molecular basis of epithelial carcinogenesis shedding light on the tumor
      initiating events. The latter may reveal novel molecular targets with clinical
      benefit. Besides, since this method can be incorporated in a wide range of low,
      medium or high-throughput image-based approaches, we expect it to be broadly
      applicable.

PMID- 29321006
TI  - The quality of working life questionnaire for cancer survivors (QWLQ-CS):
      factorial structure, internal consistency, construct validity and
      reproducibility.
AB  - BACKGROUND: To assess the factorial structure, internal consistency, construct
      validity and reproducibility of the Quality of Working Life Questionnaire for
      Cancer Survivors (QWLQ-CS). METHODS: An Exploratory Factor Analysis (EFA) was
      performed on QWLQ-CS data from a sample of employed cancer survivors to establish
      the final number of items and factorial structure of the QWLQ-CS. Internal
      consistency was assessed using Cronbach's alpha. In a second sample of (self
      )employed cancer survivors, construct validity was tested by convergent validity
      (correlations of QWLQ-CS with construct-related questionnaires), and
      discriminative validity (difference in QWLQ-CS scores between cancer survivors
      and employed people without cancer). In a subgroup of stable cancer survivors
      subtracted from the second sample, reproducibility was evaluated by Intraclass
      Correlation Coefficient (ICC) and Standard Error of Measurement (SEM). RESULTS:
      EFA on QWLQ-CS data of 302 cancer survivors resulted in 23 items and five
      factors. The internal consistency of the QWLQ-CS was Cronbach's alpha = 0.91.
      Convergent validity on data of 130 cancer survivors resulted in r = 0.61-0.70.
      QWLQ-CS scores of these cancer survivors statistically differed (p = 0.04) from
      employed people without cancer (N = 45). Reproducibility of QWLQ-CS data from 87
      cancer survivors demonstrated an ICC of 0.84 and a SEM of 9.59. CONCLUSIONS: The
      five-factor QWLQ-CS with 23 items and adequate internal consistency, construct
      validity, and reproducibility at group level can be used in clinical and
      occupational healthcare, and research settings.

PMID- 29321005
TI  - The impact of regular school closure on seasonal influenza epidemics: a data
      driven spatial transmission model for Belgium.
AB  - BACKGROUND: School closure is often considered as an option to mitigate influenza
      epidemics because of its potential to reduce transmission in children and then in
      the community. The policy is still however highly debated because of
      controversial evidence. Moreover, the specific mechanisms leading to mitigation
      are not clearly identified. METHODS: We introduced a stochastic spatial age
      specific metapopulation model to assess the role of holiday-associated behavioral
      changes and how they affect seasonal influenza dynamics. The model is applied to
      Belgium, parameterized with country-specific data on social mixing and travel,
      and calibrated to the 2008/2009 influenza season. It includes behavioral changes
      occurring during weekend vs. weekday, and holiday vs. school-term. Several
      experimental scenarios are explored to identify the relevant social and
      behavioral mechanisms. RESULTS: Stochastic numerical simulations show that
      holidays considerably delay the peak of the season and mitigate its impact.
      Changes in mixing patterns are responsible for the observed effects, whereas
      changes in travel behavior do not alter the epidemic. Weekends are important in
      slowing down the season by periodically dampening transmission. Christmas
      holidays have the largest impact on the epidemic, however later school breaks may
      help in reducing the epidemic size, stressing the importance of considering the
      full calendar. An extension of the Christmas holiday of 1 week may further
      mitigate the epidemic. CONCLUSION: Changes in the way individuals establish
      contacts during holidays are the key ingredient explaining the mitigating effect
      of regular school closure. Our findings highlight the need to quantify these
      changes in different demographic and epidemic contexts in order to provide
      accurate and reliable evaluations of closure effectiveness. They also suggest
      strategic policies in the distribution of holiday periods to minimize the
      epidemic impact.

PMID- 29321007
TI  - Staging laparoscopy for locally advanced gastric cancer in Chinese patients: a
      multicenter prospective registry study.
AB  - BACKGROUND: Staging laparoscopy(SL) is a recommended technique for the staging of
      Gastric Cancer(GC) and provides the indication for a radical surgery. Considering
      the medical practice in China, the standardized and regular usage of SL is yet to
      be spread. However, existing guidelines vary and make an ambiguity of indication
      for SL. Besides, the specific indication for Chinese patients remains a niche.
      This study aims to the essential, missing information of Chinese patients and
      tries to normalize the indication of LS in medical practice in China. METHODS:
      The study is a prospective, multicenter cohort study being conducted in China
      with a total of 450 patients, all diagnosed with locally advanced gastric cancer
      (cT2-4 N0-3 M0, no evidence of intra-abdominal dissemination) through Computed
      Tomography(CT) and/or Endoscopic Ultrasonography(EUS). Peritoneal lavage is
      regularly performed during the SL. Multivariate Cox regression model and receiver
      operator characteristic(ROC) analysis will be used to analyze the significant
      risk factors of intra-abdominal metastasis(including peritoneal dissemination and
      a positive cytological result). DISCUSSION: This confirmatory study will provide
      us with the specific positive rate of intraabdominal metastasis of GC in China,
      compared with empirical evidence of 20%. We expect this trial will contribute to
      our discovery of the specific risk factors of intra-abdominal metastasis of
      Chinese patients and to the stimulating and performing of minimally invasive
      surgical procedures. TRIAL REGISTRATION: ClinicalTrials.gov : registration number
      NCT02172690 .

PMID- 29321008
TI  - Effects of a culturally specific tobacco cessation intervention among African
      American Quitline enrollees: a randomized controlled trial.
AB  - BACKGROUND: African Americans suffer disproportionately from tobacco-related
      illness and have more difficulty quitting smoking than other racial/ethnic
      groups. Previous research indicates that African American treatment-seekers are
      high utilizers of tobacco quitlines, yet cessation rates via quitlines are lower
      relative to whites. The goal of the present study is to test the effectiveness of
      adding a culturally specific, video-based, adjunct to standard quitline care. It
      is hypothesized that the integration of an evidence-based intervention (Pathways
      to Freedom: Leading the Way to a Smoke-Free Community(c); PTF) into quitline
      services will increase cessation and treatment engagement compared to control
      conditions, and that effects will be moderated by sociocultural factors (e.g.,
      culturally specific intervention expectancies, acculturation, and ethnic
      identity). METHODS: This study is a 3-arm semi-pragmatic randomized controlled
      trial (RCT). Participants will be 1050 enrollees in the North Carolina State
      quitline (QuitlineNC) who self-identify as African American. Usual quitline care
      includes up to 4 proactive quit coaching calls, website access, and two-weeks of
      nicotine patch therapy. Eligible study participants will be randomized to receive
      (1) standard quitline services plus PTF (PTF); (2) quitline services plus a
      standard tobacco cessation DVD (attention control); or (3) quitline services
      alone (usual care). Assessments will be conducted at baseline, 3 and 6-months
      post-enrollment. The primary outcome will be biochemically verified 7 day ppa at
      6-months. Generalized linear mixed models (GLMMs) and hierarchical logistic
      regression will be used to assess the effects of treatment group on cessation
      outcomes and to test potential moderators. DISCUSSION: This study will answer
      questions regarding the implementation and effectiveness of integrating a
      culturally specific video intervention into a real-world, population-level
      tobacco intervention. It will also aid our understanding of individual-difference
      variables that are associated with success. If an incremental benefit is found,
      this trial will have implications for increasing the responsiveness of tobacco
      quitlines for African Americans, reducing tobacco cessation disparities, and best
      practices for improving minority health. In addition, the PTF intervention has
      the potential for widespread disseminated through quitlines, which are available
      across the United States. TRIAL REGISTRATION: Clinicaltrials.gov NCT03064971 .
      Registered on February 22, 2017.

PMID- 29321011
TI  - Attractive toxic sugar baits for controlling mosquitoes: a qualitative study in
      Bagamoyo, Tanzania.
AB  - BACKGROUND: Malaria elimination is unlikely to be achieved without the
      implementation of new vector control interventions capable of complementing
      insecticide-treated nets and indoor residual spraying. Attractive-toxic sugar
      baits (ATSBs) are considered a new vector control paradigm. They are
      technologically appropriate as they are simple and affordable to produce. ATSBs
      kill both female and male mosquitoes attracted to sugar feed on a sugary solution
      containing a mosquitocidal agent and may be used indoors or outdoors. This study
      explored the views and perceptions on ATSBs of community members from three
      Coastal Tanzanian communities. METHODS: Three communities were chosen to
      represent coastal urban, peri-urban and rural areas. Sensitization meetings were
      held with a total of sixty community members where ATSBs were presented and
      explained their mode of action. At the end of the meeting, one ATSB was given to
      each participant for a period of 2 weeks, after which they were invited to
      participate in focus group discussions (FGDs) to provide feedback on their
      experience. RESULTS: Over 50% of the participants preferred to use the bait
      indoors although they had been instructed to place it outdoors. Participants who
      used the ATSBs indoors reported fewer mosquitoes inside their homes, but were
      disappointed not to find the dead mosquitoes in the baits, although they had been
      informed that this was unlikely to happen. Most participants disliked the
      appearance of the bait and some thought it to be reminiscent of witchcraft.
      Neighbours that did not participate in the FGDs or sensitizations were sceptical
      of the baits. CONCLUSIONS: This study delivers insight on how communities in
      Coastal Tanzania are likely to perceive ATSBs and provides important information
      for future trials investigating the efficacy of ATSBs against malaria. This new
      vector control tool will require sensitization at community level regarding its
      mode of action in order to increase the acceptance and confidence in ATSBs for
      mosquito control given that most people are not familiar with the new paradigm. A
      few recommendations for product development and delivery are discussed.

PMID- 29321010
TI  - Evaluation of five CAD/CAM materials by microstructural characterization and
      mechanical tests: a comparative in vitro study.
AB  - BACKGROUND: Polymer infiltrated ceramics and nano-ceramic resins are the new
      restorative materials which have been developed in order to enhance the adverse
      properties of glass-matrix ceramics and resin composites. The aim of the present
      in vitro study was to evaluate the characteristics of various CAD/CAM materials
      through mechanical, microstructural, and SEM analysis. METHODS: Five test groups
      (n = 22) were formed by using the indicated CAD/CAM blocks: VITA Enamic (VITA
      Zahnfabrik), Lava Ultimate (3 M ESPE), IPS e.max CAD (Ivoclar Vivadent), IPS
      Empress CAD (Ivoclar Vivadent), and VITA Mark II (VITA Zahnfabrik). Two specimens
      from each test group were used for XRD and EDS analysis. Remaining samples were
      divided into two subgroups (n = 10). One subgroup specimens were thermocycled (5 
      degrees C to 55  degrees C, 30s, 10,000 cycles) whereas the other were not. All
      of the specimens were evaluated in terms of flexural strength, Vickers hardness,
      and fracture toughness. Results were statistically analyzed using two-way ANOVA,
      one-way ANOVA, Tukey's HSD, and Student's t tests (alpha = .05). Fractured
      specimens were evaluated using SEM. RESULTS: The highest Vickers microhardness
      value was found for VITA Mark II (p < .001), however flexural strength and
      fracture toughness results were lowest conversely (p < .05). IPS e.max CAD was
      found to have the highest flexural strength (p < .001). Fracture toughness of IPS
      e.max CAD was also higher than other tested block materials (p < .001). Lava
      Ultimate and VITA Enamic's mechanical properties were affected negatively from
      thermocycling (p < .05). Microhardness, flexural strength, and fracture toughness
      values of Lava Ultimate and VITA Enamic were found to be similar to VITA Mark II
      and IPS Empress CAD groups. CONCLUSIONS: It should be realised that simulated
      aging process seem to affect ceramic-polymer composite materials more
      significantly than glass ceramics.

PMID- 29321009
TI  - Dual action of highbush blueberry proanthocyanidins on Aggregatibacter
      actinomycetemcomitans and the host inflammatory response.
AB  - BACKGROUND: The highbush blueberry (Vaccinium corymbosum) has a beneficial effect
      on several aspects of human health. The present study investigated the effects of
      highbush blueberry proanthocyanidins (PACs) on the virulence properties of
      Aggregatibacter actinomycetemcomitans and macrophage-associated inflammatory
      responses. METHODS: PACs were isolated from frozen highbush blueberries using
      solid-phase chromatography. A microplate dilution assay was performed to
      determine the effect of highbush blueberry PACs on A. actinomycetemcomitans
      growth as well as biofilm formation stained with crystal violet. Tight junction
      integrity of oral keratinocytes was assessed by measuring the transepithelial
      electrical resistance (TER), while macrophage viability was determined with a
      colorimetric MTT assay. Pro-inflammatory cytokine and MMP secretion by A.
      actinomycetemcomitans-stimulated macrophages was quantified by ELISA. The U937
      3xkappaB-LUC monocyte cell line transfected with a luciferase reporter gene was
      used to monitor NF-kappaB activation. RESULTS: Highbush blueberry PACs reduced
      the growth of A. actinomycetemcomitans and prevented biofilm formation at sub
      inhibitory concentrations. The treatment of pre-formed biofilms with the PACs
      resulted in a loss of bacterial viability. The antibacterial activity of the PACs
      appeared to involve damage to the bacterial cell membrane. The PACs protected the
      oral keratinocytes barrier integrity from damage caused by A.
      actinomycetemcomitans. The PACs also protected macrophages from the deleterious
      effect of leukotoxin Ltx-A and dose-dependently inhibited the secretion of pro
      inflammatory cytokines (IL-1beta, IL-6, CXCL8, TNF-alpha), matrix
      metalloproteinases (MMP-3, MMP-9), and sTREM-1 by A. actinomycetemcomitans
      treated macrophages. The PACs also inhibited the activation of the NF-kappaB
      signaling pathway. CONCLUSION: The antibacterial and anti-inflammatory properties
      of highbush blueberry PACs as well as their ability to protect the oral
      keratinocyte barrier and neutralize leukotoxin activity suggest that they may be
      promising candidates as novel therapeutic agents.

PMID- 29321012
TI  - Adaptation of child oral health education leaflets for Arabic migrants in
      Australia: a qualitative study.
AB  - BACKGROUND: The purpose of this study was to gain an in-depth understanding of
      Arabic-speaking mothers views on the usefulness of existing oral health education
      leaflets aimed at young children and also to record their views on the tailored
      versions of these leaflets. METHODS: This qualitative study was nested within a
      large ongoing birth cohort study in South Western Sydney, Australia. Arabic
      speaking mothers (n = 19) with young children were purposively selected and
      approached for a semi-structured interview. Two original English leaflets giving
      advice on young children's oral health were sent to mother's prior to the
      interview. On the day of interview, mothers were given simplified-English and
      Arabic versions of both the leaflets and were asked to compare the three
      versions. Interviews were audio-recorded, subsequently transcribed verbatim and
      analysed by thematic analysis. Ethical approval was obtained from Human Research
      Ethics Committees of the former Sydney South West Area Health Service, University
      of Sydney and Western Sydney University. RESULTS: Mothers reported that
      simplified English together with the Arabic version of the leaflets were useful
      sources of information. Although many mothers favoured the simplified version
      over original English leaflets, the majority favoured the leaflets in Arabic.
      Ideally, a "dual Arabic - simplified English leaflet" was preferred. The
      understanding of key health messages was optimised through a simple layout and
      visual images. CONCLUSIONS: There is a need to tailor oral health education
      leaflets for Arabic-speaking migrants. Producers of dental leaflets should also
      consider a "dual Arabic - simplified English leaflet" to improve oral health
      knowledge of Arabic-speaking migrants. The use of simple layout and pictures
      assists Arabic-speaking migrants to understand the content of dental leaflets.

PMID- 29321013
TI  - Hemoglobin level and lipoprotein particle size.
AB  - BACKGROUND: Alterations in lipoprotein size are associated with increased
      cardiovascular disease risk. Higher hemoglobin levels may indicate a higher risk
      of atherosclerosis and was previously associated with obesity, metabolic
      syndrome, and insulin resistance. No previous studies have investigated an
      association between hemoglobin concentration and lipoprotein particle size.
      METHODS: We conducted a population-based, cross-sectional study of 766 Caucasian,
      middle-aged subjects (341 men and 425 women) born in Pieksamaki, Finland, who
      were categorized into five age groups. The concentrations and sizes of
      lipoprotein subclass particles were analyzed by high-throughput nuclear magnetic
      resonance (NMR) spectroscopy. RESULTS: Larger very low density lipoprotein (VLDL)
      particle diameter was associated with higher hemoglobin concentrations in men (p
      = 0.003). There was a strong relationship between smaller high density
      lipoprotein (HDL) particle size and higher hemoglobin concentration in both men
      and women as well as with smaller low density lipoprotein (LDL) particle size and
      higher hemoglobin concentration in men and women (p < 0.001; p = 0.009, p =
      0.008). VLDL particle concentration had a moderate positive correlation with
      hemoglobin concentration (r = 0.15; p < 0.001). LDL particle concentration showed
      a statistical trend suggesting increasing particle concentration with increasing
      hemoglobin levels (r = 0.08; p = 0.05). CONCLUSION: Higher hemoglobin levels are
      associated with larger VLDL, smaller LDL, and smaller HDL particle sizes and
      increasing amounts of larger VLDL and smaller LDL particles. This suggests that a
      higher hemoglobin concentration is associated with an unfavorable lipoprotein
      particle profile that is part of states that increase cardiovascular disease risk
      like diabetes and metabolic syndrome.

PMID- 29321014
TI  - Current status of nylon teeth myth in Tanzania: a cross sectional study.
AB  - BACKGROUND: Nylon teeth myth is a belief of associating infant illnesses with
      bulges on infants' alveolus that mark the positions of underlying developing
      teeth and that it is necessary to treat the condition mainly by traditional
      healers to prevent infant death. The traditional treatment often leads to serious
      complications that may lead to infant death. Although the government instituted
      educational campaigns against the myth in 1980s to 1990s, to date, repeated
      unpublished reports from different parts of the country indicate continued
      existence of the myth. Therefore, this study aimed to assess the current status
      of the nylon teeth myth in Tanzania. METHODS: The study population was obtained
      using the WHO Oral Health pathfinder methodology. A structured questionnaire
      inquired about socio-demographics as well as experiences with "nylon teeth" myth
      and its related practices. Odds ratios relating to knowledge and experience of
      the nylon teeth myth were estimated. RESULTS: A total of 1359 respondents aged 17
      to 80 years participated in the study. 614 (45%) have heard of nylon teeth myth,
      of whom 46.1% believed that nylon teeth is a reality, and 42.7% reported
      existence of the myth at the time of study. Being residents in regions where
      nylon teeth myth was known before 1990 (OR = 8.39 (6.50-10.83), p < 0.001) and/or
      hospital worker (OR = 2.97 (1.99-4.42), p < 0.001) were associated with having
      have heard of nylon teeth myth. Proportionately more residents in regions where
      nylon teeth myth was not known before 1990 (p < 0.001), the educated (p < 0.001)
      and hospital workers (p < 0.001) believed modern medicine, whereas,
      proportionately more residents in regions where nylon teeth was known before 1990
      (p < 0.001), less educated (p < 0.001) and non-hospital workers (p < 0.001)
      believed traditional medicine to be the best treatment for symptoms related to
      nylon teeth myth respectively. CONCLUSION: The "nylon teeth" myth still exists in
      Tanzania; a substantial proportion strongly believe in the myth and consider
      traditional medicine the best treatment of the myth related conditions.

PMID- 29321015
TI  - Differentials in health-related quality of life of employed and unemployed women
      with normal vaginal delivery.
AB  - BACKGROUND: The combination of child care and domestic work demands on both
      housewives and the employed (hired) women may impact their health-related quality
      of-life. There is paucity of studies to ascertain this. This study investigated
      the differences in health-related quality of life of employed and unemployed
      women with normal vaginal delivery and associated socio-demographic variables.
      METHODS: This longitudinal study was done from March, 2012 to June, 2013.
      Modified SF-36v2TM health-related quality of life questionnaire was administered
      to 234 newly delivered women drawn from six selected hospitals in Enugu,
      Southeast Nigeria at 6, 12 and 18 weeks postpartum. Respondents were reached for
      data collection through personal contacts initially at the hospitals of delivery,
      and subsequently by visits to their homes/workplaces or cell-phone calls. Women
      were asked to indicate how each of 36 items applied to them at each of the three
      times. Data collection lasted for six calendar months and 17 days (from September
      3rd 2012 to 20th March, 2013). RESULTS: All the women had their best HrQoL at 12
      weeks postpartum. Employed women reported lower health-related quality-of-life
      than the unemployed at the three time-points, the lowest mean score being at 18
      weeks postpartum (Mean = 73.9). Multiple comparison of scores of the two groups
      using Tukey HSD Repeated Mean showed significant variation on the eight subscales
      of the health-related quality-of-life. Physical functioning (p = 0.045), Physical
      role limitation (p = 0.000), bodily pain (p = 0.000), social functioning (p =
      0.000) and general health (p = 0.000) were unequal guaranteeing type 1 error.
      Women with higher education and personal income reported higher health-related
      quality-of-life (p < 0.05). Employed women have more problems with physical
      health components and are more negatively affected by increasing age except those
      with higher education and personal income. CONCLUSIONS: Increased
      responsibilities combined with increasing age and low socio-economic status
      reduce women's health-related quality-of-life post-partum. The traditionally
      accepted paid 3 months maternity leave should be elongated by extra months to
      help women balance their daily work with baby care. Gender sensitive employment
      opportunities in favour of women are necessary to empower more women
      economically.

PMID- 29321016
TI  - Long lasting insecticidal net use and its associated factors in Limmu Seka
      District, South West Ethiopia.
AB  - BACKGROUND: Many countries in sub-Saharan Africa, including Ethiopia, are
      focusing on the distribution of Long Lasting Insecticidal Nets (LLINs) to combat
      malaria. However, utilization of the LLIN is low when compared with LLIN
      possession because of various factors. This study was conducted to measure the
      actual LLIN usage and identify factors associated with its utilization in Limmu
      Seka District, South West Ethiopia. METHODS: A community based cross-sectional
      survey was conducted among 830 households from December 25, 2011 to February 29,
      2012. RESULTS: A total of 830 households were selected by stratified systematic
      sampling and surveyed. Ninety percent of those surveyed owned LLINs and 68.3%
      reported that someone had slept under the net on the night prior to the survey.
      The factors associated with LLIN usage were knowledge of the mode of malaria
      transmission (AOR; 0.086, 95% CI 0.03, 0.24), the preferred conical shapes of the
      LLIN (AOR; 1.6, 95% CI 1.31, 4.1), receiving information about their use from
      Health Extension Workers (HEWs) (AOR; 2.4, 95% CI 1.5, 3.9), hearing media
      campaigns (AOR; 3.2 95% CI 3.5, 9.2), education at a health facility (AOR; 2 95%
      CI 1.5, 3.9) or having a family size of three or less (AOR; 2.1, 95% CI 1.3,
      3.5). CONCLUSION: Although ownership of Long Lasting Insecticidal Nets was high
      at 90%, the actual usage of LLIN was low, and not all family members were
      protected. Promoting the usage of LLINs utilization by those at most risk,
      especially the conical shaped ones, through intensified health education using
      HEWs and mass media campaigns at all health facilities, schools and communities
      will improve LLIN utilization.

PMID- 29321017
TI  - Influence of the child's perceived general health on the primary caregiver's
      health status.
AB  - BACKGROUND: In estimating the impact of an intervention, ignoring the effect of
      improving the health of one member of the caregiver/child dyad on the Health
      Related Quality of Life (HRQoL) of the other member may lead to an
      underestimation of the utility gained. This may be particularly true for
      infants/young children and their caregivers. The aim of this study was to
      quantify the interaction between the child's perceived general health as assessed
      by the newly developed Toddler and Infant Questionnaire (TANDI) on the reporting
      of the caregiver's own HRQoL as assessed by the EQ-5D-3 L. METHODS: A sample of
      187 caregivers participated. A total of 60 caregivers of acutely-ill (AI) and 60
      caregivers of chronically-ill (CI) children were recruited from a children's
      hospital. The 67 caregivers of general population (GP) children were recruited at
      a pre-school. Each caregiver completed the proxy rating of their child's HRQoL on
      the TANDI (The TANDI is an experimental HRQoL instrument, modelled on the EQ-5D-Y
      proxy, for children aged 1-36 months), which comprises of six dimensions of
      health and a rating of general health on a Visual Analogue Scale (VAS). The
      caregiver completed the EQ-5D-3 L, a self-report measure of their own HRQoL.
      Forward stepwise regression models were developed with 1) the VAS score of the
      caregiver and 2) the VAS score of the child as dependent variables. The
      independent variables for the caregiver included dummy variables for the presence
      or absence of problems on the EQ-5D-3 L and the VAS score of the child. The
      independent variables for the child included dummy variables for each TANDI
      dimension and the VAS of the caregiver. RESULTS: The TANDI results indicated that
      in five of the six dimensions AI children had more problems than the other two
      groups and the GP children were reported to have a significantly higher VAS than
      the other two groups. The child's VAS was significantly correlated with the
      caregiver's VAS in all groups, but most strongly in the AI group. The preference
      based scores (using the UK TTO tariff) were only correlated in the AI group. The
      inclusion of the child's VAS increased the variance accounted for 11% of the VAS
      score of the caregiver. Anxiety and depression was the only dimension which
      accounted for more variance (18%). Similarly the perceived health state, VAS of
      the caregiver accounted for 14% of the variance in the child's VAS, second only
      to problems with play (25%). CONCLUSION: There does indeed appear to be a strong
      relationship between the VAS scores of the children and their caregivers. The
      perceived general health of the child influences the caregivers reporting of
      their general health, more than their own report of experiencing pain or
      discomfort or problems with mobility. Thus, improving the HRQoL of the very young
      child may improve the caregiver's HRQoL as well. Conversely, if the caregiver has
      a lower perceived HRQoL this may result in a decrement in the reported VAS of the
      child, independent of the presence or absence of problems in the different
      dimensions. This improvement is not currently captured by Cost Utility Analysis
      (CUA). It is recommended that future research investigates this effect with
      regards to CUA calculations.

PMID- 29321018
TI  - Management and attitudes about IPF (Idiopathic Pulmonary Fibrosis) among
      physicians from Latin America.
AB  - BACKGROUND: The aim of our study was to assess current practice patterns and
      attitudes towards diagnosis and management of idiopathic pulmonary fibrosis (IPF)
      patients in Latin America. METHODS: A Cross-sectional survey was developed and up
      to 455 physicians were enrolled. We used a rigorous method of validation using
      the translated version of the AIR Survey. RESULTS: Mean age was 47.5 years (SD
      12.6) with 20.4 years (SD 12.3) of practice. In around 30% of physicians were
      reported access to radiologist, pathologist and multidisciplinary team. Despite
      almost all physicians reported that (ATS/ERS/JRS/ALAT) guidelines are useful,
      half of them prescribed corticoids for treatment of disease. Most respondents
      (69.9%) reported cough as the presenting symptom. Around 80% considered IPF to be
      an important clinical disorder, and felt that identifying patients at risk for
      IPF was important or extremely important. However, only 59.7% felt confident in
      managing patients with IPF, and similar numbers (60.8%) felt confident about
      their knowledge. Pulmonologist have more confidence and management of IPF that no
      pulmonologist. CONCLUSION: The results of this survey of Latin American
      physicians could help to fill gaps regarding awareness, management and treatment
      of IPF and improve earlier diagnosis of IPF.

PMID- 29321019
TI  - A qualitative study on coping behaviors and influencing factors among mothers in
      Japan raising children under three years old while experiencing physical and
      mental subjective symptoms.
AB  - BACKGROUND: No studies illustrating the coping behaviors of mothers experiencing
      physical and mental subjective symptoms, or the factors that contribute to these
      behaviors, have been investigated. Therefore, the present study sought to develop
      a conceptual framework on the coping behaviors and contributing factors of
      mothers experiencing physical and mental subjective symptoms. METHODS: This
      qualitative study involved theoretical sampling and semi-structured interviews of
      mothers who were raising children under 3 years of age in Japan and had
      experienced physical and mental subjective symptoms since giving birth. Women who
      were pregnant, required regular medical exams, or had difficulty communicating in
      Japanese were excluded. All mothers were recruited via personal contacts,
      snowball sampling, and posters at a community center and nursery schools.
      Analysis was conducted using the constant comparative method. The interview data
      were extracted in contextual units based on analytical themes, and concepts were
      generated. Relationships between concepts were investigated and categorized. To
      confirm theoretical saturation and ensure the validity of the data, a study
      supervisor was appointed, four qualitative researchers examined the results, and
      the interview respondents underwent member checking. RESULTS: There were a total
      of 21 participants. Thirteen categories were created from 29 concepts identified
      from the analytical theme "What do mothers do when raising children under 3 years
      of age while experiencing physical and mental subjective symptoms?" While
      experiencing subjective symptoms, mothers raising children under 3 years of age
      tended to lead a child-centric lifestyle and were hesitant to visit the doctor,
      not only because of typical reasons such as time and costs, but also because of
      factors related to their child. Some circumstances occurring while experiencing
      physical and mental subjective symptoms led mothers to put their own needs first
      and attempt to cope on their own as much as possible. As a result, most mothers
      would only visit a doctor after becoming seriously ill. CONCLUSION: Mothers
      raising children under 3 years of age in Japan tend to put their own needs on
      hold when experiencing subjective symptoms. As a result, they attempt to cope on
      their own and, at times, only visit a doctor after becoming seriously ill.

PMID- 29321020
TI  - Meta-analysis of human gene expression in response to Mycobacterium tuberculosis
      infection reveals potential therapeutic targets.
AB  - BACKGROUND: With the global emergence of multi-drug resistant strains of
      Mycobacterium tuberculosis, new strategies to treat tuberculosis are urgently
      needed such as therapeutics targeting potential human host factors. RESULTS: Here
      we performed a statistical meta-analysis of human gene expression in response to
      both latent and active pulmonary tuberculosis infections from nine published
      datasets. We found 1655 genes that were significantly differentially expressed
      during active tuberculosis infection. In contrast, no gene was significant for
      latent tuberculosis. Pathway enrichment analysis identified 90 significant
      canonical human pathways, including several pathways more commonly related to non
      infectious diseases such as the LRRK2 pathway in Parkinson's disease, and PD-1/PD
      L1 signaling pathway important for new immuno-oncology therapies. The analysis of
      human genome-wide association studies datasets revealed tuberculosis-associated
      genetic variants proximal to several genes in major histocompatibility complex
      for antigen presentation. We propose several new targets and drug-repurposing
      opportunities including intravenous immunoglobulin, ion-channel blockers and
      cancer immuno-therapeutics for development as combination therapeutics with anti
      mycobacterial agents. CONCLUSIONS: Our meta-analysis provides novel insights into
      host genes and pathways important for tuberculosis and brings forth potential
      drug repurposing opportunities for host-directed therapies.

PMID- 29321021
TI  - Silver-pig skin nanocomposites and mesenchymal stem cells: suitable antibiofilm
      cellular dressings for wound healing.
AB  - BACKGROUND: Treatment of severe or chronic skin wounds is an important challenge
      facing medicine and a significant health care burden. Proper wound healing is
      often affected by bacterial infection; where biofilm formation is one of the main
      risks and particularly problematic because it confers protection to
      microorganisms against antibiotics. One avenue to prevent bacterial colonization
      of wounds is the use of silver nanoparticles (AgNPs); which have proved to be
      effective against non-multidrug-resistant and multidrug-resistant bacteria. In
      addition, the use of mesenchymal stem cells (MSC) is an excellent option to
      improve wound healing due to their capability for differentiation and release of
      relevant growth factors. Finally, radiosterilized pig skin (RPS) is a biomatrix
      successfully used as wound dressing to avoid massive water loss, which represents
      an excellent carrier to deliver MSC into wound beds. Together, AgNPs, RPS and MSC
      represent a potential dressing to control massive water loss, prevent bacterial
      infection and enhance skin regeneration; three essential processes for
      appropriate wound healing with minimum scaring. RESULTS: We synthesized stable 10
      nm-diameter spherical AgNPs that showed 21- and 16-fold increase in bacteria
      growth inhibition (in comparison to antibiotics) against clinical strains
      Staphylococcus aureus and Stenotrophomonas maltophilia, respectively. RPS samples
      were impregnated with different AgNPs suspensions to develop RPS-AgNPs
      nanocomposites with different AgNPs concentrations. Nanocomposites showed
      inhibition zones, in Kirby-Bauer assay, against both clinical bacteria tested.
      Nanocomposites also displayed antibiofilm properties against S. aureus and S.
      maltophilia from RPS samples impregnated with 250 and 1000 ppm AgNPs suspensions,
      respectively. MSC were isolated from adipose tissue and seeded on nanocomposites;
      cells survived on nanocomposites impregnated with up to 250 ppm AgNPs
      suspensions, showing 35% reduction in cell viability, in comparison to cells on
      RPS. Cells on nanocomposites proliferated with culture days, although the number
      of MSC on nanocomposites at 24 h of culture was lower than that on RPS.
      CONCLUSIONS: AgNPs with better bactericide activity than antibiotics were
      synthesized. RPS-AgNPs nanocomposites impregnated with 125 and 250 ppm AgNPs
      suspensions decreased bacterial growth, decreased biofilm formation and were
      permissive for survival and proliferation of MSC; constituting promising multi
      functional dressings for successful treatment of skin wounds.

PMID- 29321023
TI  - Which risk understandings can be derived from the current disharmonized
      regulation of complementary and alternative medicine in Europe?
AB  - BACKGROUND: Many European citizens are seeking complementary and alternative
      medicine (CAM). These treatments are regulated very differently in the EU/EFTA
      countries. This may demonstrate differences in how risk associated with the use
      of CAM is perceived. Since most CAM treatments are practiced fairly similarly
      across Europe, differing risk understandings may influence patient safety for
      European CAM users. The overall aim of this article is thus to contribute to an
      overview and awareness of possible differing risk understandings in the field of
      CAM at a policymaking/structural level in Europe. METHODS: The study is a re
      analysis of data collected in the CAMbrella EU FP7 document and interview study
      on the regulation of CAM in 39 European countries. The 12 CAM modalities included
      in the CAMbrella study were ranked with regard to assumed risk potential
      depending on the number of countries limiting its practice to regulated
      professions. The 39 countries were ranked according to how many of the included
      CAM modalities they limit to be practiced by regulated professions. RESULTS:
      Twelve of 39 countries generally understand the included CAM treatments to
      represent "high risk", 20 countries "low risk", while the remaining 7 countries
      understand CAM treatments as carrying "very little or no risk". The CAM
      modalities seen as carrying a risk high enough to warrant professional regulation
      in the highest number of countries are chiropractic, acupuncture, massage,
      homeopathy and osteopathy. The countries understanding most of the CAM modalities
      in the study as potentially high-risk treatments are with two exceptions
      (Portugal and Belgium) all concentrated in the southeastern region of Europe.
      CONCLUSION: The variation in regulation of CAM may represent a substantial lack
      of common risk understandings between health policymakers in Europe. We think the
      discrepancies in regulation are to a considerable degree also based on factors
      unrelated to patient risk. We argue that it is important for patient safety that
      policy makers across Europe address this confusing situation. This could be done
      by applying the WHO patient safety definitions and EU's policy to facilitate
      access to "safe and high-quality healthcare", and regulate CAM accordingly.

PMID- 29321022
TI  - Serum metabolic profiling identified a distinct metabolic signature in patients
      with idiopathic pulmonary fibrosis - a potential biomarker role for LysoPC.
AB  - BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease of
      unknown etiology. Patients present loss of lung function, dyspnea and dry cough.
      Diagnosis requires compatible radiologic imaging and, in undetermined cases,
      invasive procedures such as bronchoscopy and surgical lung biopsy. The
      pathophysiological mechanisms of IPF are not completely understood. Lung injury
      with abnormal alveolar epithelial repair is thought to be a major cause for
      activation of profibrotic pathways in IPF. Metabolic signatures might indicate
      pathological pathways involved in disease development and progression. Reliable
      serum biomarker would help to improve both diagnostic approach and monitoring of
      drug effects. METHOD: The global metabolic profiles measured by ultra high
      performance liquid chromatography coupled to high-resolution mass spectrometry
      (UHPLC-HRMS) of ten stable IPF patients were compared to the ones of ten healthy
      participants. The results were validated in an additional study of eleven IPF
      patients and ten healthy controls. RESULTS: We discovered 10 discriminative
      metabolic features using multivariate and univariate statistical analysis. Among
      them, we identified one metabolite at a retention time of 9.59 min that was two
      times more abundant in the serum of IPF patients compared to healthy
      participants. Based on its ion pattern, a lysophosphatidylcholine (LysoPC) was
      proposed. LysoPC is a precursor of lysophosphatidic acid (LPA) - a known mediator
      for lung fibrosis with its pathway currently being evaluated as new therapeutic
      drug target for IPF and other fibrotic diseases. CONCLUSIONS: We identified a
      LysoPC by UHPLC-HRMS as potential biomarker in serum of patients with IPF.
      Further validation studies in a larger cohort are necessary to determine its role
      in IPF. TRIAL REGISTRATION: Serum samples from IPF patients have been obtained
      within the clinical trial NCT02173145 at baseline and from the idiopathic
      interstitial pneumonia (IIP) cohort study. The study was approved by the Swiss
      Ethics Committee, Bern (KEK 002/14 and 246/15 or PB_2016-01524).

PMID- 29321024
TI  - Interprofessional education in graduate medical education: survey study of
      residency program directors.
AB  - BACKGROUND: The overarching purpose of this study is to examine the current
      trends in interprofessional education (IPE) within graduate medical education in
      the Unites States. METHODS: A survey was sent to program directors across with
      different specialties between March and April 2016. The survey was completed by
      233 out of 1757 program directors, which represents a response rate of 13.3%.
      RESULTS: IPE is currently being used by over 60% of the GME program directors
      that completed the survey. The median number of IPE hours is 60. Classroom
      learning (70.8%) and team-based approaches (70.1%) to patient care are the two
      most common forms of IPE. The two most prevalent reasons for implementing IPE are
      improving collaboration (92.2%) and communication (87%). More than half of the
      program directors agreed or strongly agreed that lack of time both for teachers
      (54.4) and for residents (51.5%) are barriers to IPE. About one third of the
      respondents whose programs do not include IPE are interested in implementing some
      IPE in the future. CONCLUSION: IPE in its varying formats has been implemented as
      a training model by many residency programs. Further studies are needed to
      explore the comparative effectiveness of the different modalities of IPE.

PMID- 29321025
TI  - Diagnostic challenges of prolonged post-treatment clearance of Plasmodium nucleic
      acids in a pre-transplant autosplenectomized patient with sickle cell disease.
AB  - BACKGROUND: Autosplenectomy, as a result of sickle cell disease, is an important
      risk factor for severe malaria. While molecular methods are helpful in providing
      rapid and accurate infection detection and species identification, the effect of
      hyposplenism on result interpretation during the course of infection should be
      carefully considered. CASE PRESENTATION: A 32-year old autosplenectomized
      Nigerian male with severe sickle cell disease was referred to the National
      Institutes of Health for allogenic hematopoietic stem cell transplant. Despite
      testing negative for malaria by both smear and PCR 2 weeks after arrival in the
      USA, the patient developed fever and diffuse bilateral lower rib cage and upper
      abdominal pain 2 weeks later and subsequently tested positive for Plasmodium
      falciparum. Parasitaemia was tracked over time by microscopy and nucleic acid
      tests to evaluate the therapeutic response in the setting of hyposplenism. The
      patient showed prompt resolution of patent infection by microscopy but remained
      positive by molecular methods for > 30 days after treatment initiation.
      CONCLUSION: While molecular testing can provide sensitive Plasmodium nucleic acid
      detection, the persistence of Plasmodium nucleic acids following adequate
      treatment in functionally asplenic patients can lead to a diagnostic dilemma. In
      such patients, clinical response and peripheral blood smears should guide patient
      management following treatment. Nonetheless, in pre-transplant patients at high
      risk for pre-existing Plasmodium infections, highly sensitive molecular assays
      can be useful to rule out infection prior to transplantation.

PMID- 29321027
TI  - The role of transportation in the spread of Brachyspira hyodysenteriae in
      fattening farms.
AB  - BACKGROUND: Direct and indirect contact among animals and holdings are important
      in the spread of Brachyspira hyodysenteriae. The objective of this study was to
      investigate the role of slaughterhouse vehicles in spreading B. hyodysenteriae
      between unconnected farms. RESULTS: Multilocus sequence typing (MLST) and
      Multiple Locus Variable number tandem repeat Analysis (MLVA) were used to
      characterize B. hyodysenteriae strains isolated from trucks. Before cleaning, 976
      batches of finishing pigs transported by 174 trucks from 540 herds were sampled.
      After cleaning, 763 of the 976 batches were also sampled. Sixty-one of 976 and 4
      of 763 environmental swabs collected from trucks before and after cleaning and
      disinfection operations, respectively, were positive for B. hyodysenteriae. The
      65 isolates in this study originated from 48 farms. Trucks were classified into
      five categories based on the number of visited farms as follows: category 1: 1-5
      farms, category 2: 6-10 farms, category 3: 11-15 farms, category 4: 16-20 farms,
      category 5: >21 farms. Although the largest number of vehicles examined belonged
      to category 1, the highest percentage of vehicles positive for B. hyodysenteriae
      was observed in categories 3, 4 and 5. Specifically, 90.9% of trucks belonging to
      category 5 were positive for B. hyodysenteriae, followed by categories 4 and 3
      with 85.7% and 83.3%, respectively. The results of MLST and MLVA suggest that
      trucks transporting pigs from a high number of farms also play a critical role in
      spreading different B. hyodysenteriae genetic profiles. STVT 83-3, which seems to
      be the current dominant type in Italy, was identified in 56.25% of genotyped
      isolates. The genetic diversity of isolated strains from trucks was high,
      particularly, in truck categories 3, 4 and 5. This result confirmed that MLST and
      MLVA can support the study of epidemiological links between different B.
      hyodysenteriae farm strains. CONCLUSIONS: This study highlights the potential
      role of shipments in B. hyodysenteriae spread. Moreover, it emphasizes the
      importance of strict vehicle hygiene practices for biosecurity programmes.

PMID- 29321028
TI  - Health condition and familial factors associated with health-related quality of
      life in adolescents with congenital heart disease: a cross sectional study.
AB  - BACKGROUND: The focus of clinical care after the repair of congenital heart
      disease has shifted from saving life of the patient to the patient's quality of
      life. The purpose of this study was to examine the health condition and familial
      factors associated with the health related quality of life of adolescents with
      congenital heart disease. METHODS: Ninety-eight adolescents aged 13-19 years were
      collected from a congenital heart clinic from July 22 to August 23, 2013.
      Perceptions of parental rearing behaviors, health related quality of life of
      adolescent with congenital heart disease, and general characteristics were
      measured. We used multiple linear regression analysis to explore factors that are
      associated with the health related quality of life of adolescents with congenital
      heart disease. RESULTS: New York heart association class (Adj R2 = .186, p =
      .000), presence of siblings (Adj R2 = .240, p = .010), and mother's emotional
      warmth (Adj R2 = .265, p = .043) were significantly associated with the health
      related quality of life of adolescents with congenital heart disease.
      CONCLUSIONS: Emotionally warm parental rearing behaviors and the presence of
      siblings were important familial factors that were positively associated with
      HRQOL in adolescents with CHD. Therefore, it is important for healthcare
      providers to develop a greater sensitivity to, and awareness of, the familial
      influences that may be impacting a subject's HRQOL, as well as the exigencies of
      the CHD, itself.

PMID- 29321026
TI  - Lay health worker experiences administering a multi-level combination
      intervention to improve PMTCT retention.
AB  - BACKGROUND: The recent scale-up of prevention of mother-to-child transmission of
      HIV (PMTCT) services has rapidly accelerated antiretroviral therapy (ART) uptake
      among pregnant and postpartum women in sub-Saharan Africa. The Mother and Infant
      Retention for Health (MIR4Health) study evaluates the impact of a combination
      intervention administered by trained lay health workers to decrease attrition
      among HIV-positive women initiating PMTCT services and their infants through 6
      months postpartum. METHODS: This was a qualitative study nested within the
      MIR4Health trial. MIR4Health was conducted at 10 health facilities in Nyanza,
      Kenya from September 2013 to September 2015. The trial intervention addressed
      behavioral, social, and structural barriers to PMTCT retention and included:
      appointment reminders via text and phone calls, follow-up and tracking for missed
      clinic visits, PMTCT health education at home visits and during clinic visits,
      and retention and adherence support and counseling. All interventions were
      administered by lay health workers. We describe results of a nested small
      qualitative inquiry which conducted two focus groups to assess the experiences
      and perceptions of lay health workers administering the interventions.
      Discussions were recorded and simultaneously transcribed and translated into
      English. Data were analyzed using framework analysis approach. RESULTS: Study
      findings show lay health workers played a critical role supporting mothers in
      PMTCT services across a range of behavioral, social, and structural domains,
      including improved communication and contact, health education, peer support, and
      patient advocacy and assistance. Findings also identified barriers to the uptake
      and implementation of the interventions, such as concerns about privacy and
      stigma, and the limitations of the healthcare system including healthcare worker
      attitudes. Overall, study findings indicate that lay health workers found the
      interventions to be feasible, acceptable, and well received by clients.
      CONCLUSIONS: Lay health workers played a fundamental role in supporting mothers
      engaged in PMTCT services and provided valuable feedback on the implementation of
      PMTCT interventions. Future interventions must include strategies to ensure
      client privacy, decrease stigma within communities, and address the practical
      limitations of health systems. This study adds important insight to the growing
      body of research on lay health worker experiences in HIV and PMTCT care. TRIAL
      REGISTRATION: Clinicaltrials.gov NCT01962220 .

PMID- 29321029
TI  - Association of caries experience and dental plaque with sociodemographic
      characteristics in elementary school-aged children: a cross-sectional study.
AB  - BACKGROUND: Dental caries among Iranian elementary school children aged 6-12
      years continue to rise. To estimate treatment needs and guide health initiatives,
      current epidemiologic data are required. Such data are currently unavailable for
      dental health. The purpose of this study was to assess caries experience, dental
      plaque, and associated factors in elementary school-aged children from Iran.
      METHODS: In this cross-sectional study, 988 elementary school children aged 7-12
      years were selected by multistage cluster sampling. Dental caries was studied
      using the WHO criteria, dental plaque was examined according to O'Leary index.
      Data on parental education and occupation, living district, dental pain within
      the past year, and tooth brushing habits under parental supervision were
      collected through interviews based on questionnaire. The data were analyzed with
      descriptive statistics and logistic and linear regression. RESULTS: The mean (SD)
      age of the elementary school children was 9.64 (1.73) years. The highest dmft was
      seen in elementary school children aged 7-8 years 6.53 (4.37) and the highest
      DMFT and dental plaque was in 12 year olds recorded as 1.17 (1.77) and 51.97
      (25.86), respectively. The proportion of decayed teeth in 7 years old elementary
      school based on dmft index was 80.36%, moreover, the proportion in 12 years old
      elementary school was 40.17% based on the DMFT index. Age, gender, and dental
      pain within the past year were significantly associated with DMFT and dmft. The
      odds of developing dental caries (DMFT) was 1.70 times higher in girls than in
      boys (p < 0.001) and 1.72 times higher in the students that reported dental pain
      frequently than in those who did not (p = 0.005). The chance of developing dental
      caries (dmft) was 0.47 times lower in girls than boys (p < 0.001). Age was
      significantly correlated with dental plaque such that Plaque Index increased by
      2.44 times per one year increase in age (p < 0.001). CONCLUSION: Results
      indicated that dental caries experience and plaque formation among elementary
      school children in Hamadan were high and they were influenced by their
      sociodemographic factors. The associations found can be used as a helpful guide
      for planning accurate preventive programs for elementary school children in this
      region.

PMID- 29321030
TI  - CRABP1, C1QL1 and LCN2 are biomarkers of differentiated thyroid carcinoma, and
      predict extrathyroidal extension.
AB  - BACKGROUND: The prognostic variability of thyroid carcinomas has led to the
      search for accurate biomarkers at the molecular level. Follicular thyroid
      carcinoma (FTC) is a typical example of differentiated thyroid carcinomas (DTC)
      in which challenges are faced in the differential diagnosis. METHODS: We used
      high-throughput paired-end RNA sequencing technology to study four cases of FTC
      with different degree of capsular invasion: two minimally invasive (mFTC) and two
      widely invasive FTC (wFTC). We searched by genes differentially expressed between
      mFTC and wFTC, in an attempt to find biomarkers of thyroid cancer diagnosis
      and/or progression. Selected biomarkers were validated by real-time quantitative
      PCR in 137 frozen thyroid samples and in an independent dataset (TCGA),
      evaluating the diagnostic and the prognostic performance of the candidate
      biomarkers. RESULTS: We identified 17 genes significantly differentially
      expressed between mFTC and wFTC. C1QL1, LCN2, CRABP1 and CILP were differentially
      expressed in DTC in comparison with normal thyroid tissues. LCN2 and CRABP1 were
      also differentially expressed in DTC when compared with follicular thyroid
      adenoma. Additionally, overexpression of LCN2 and C1QL1 were found to be
      independent predictors of extrathyroidal extension in DTC. CONCLUSIONS: We
      conclude that the underexpression of CRABP1 and the overexpression of LCN2 may be
      useful diagnostic biomarkers in thyroid tumours with questionable malignity, and
      the overexpression of LCN2 and C1QL1 may be useful for prognostic purposes.

PMID- 29321031
TI  - Deprescribing preventive cardiovascular medication in patients with predicted low
      cardiovascular disease risk in general practice - the ECSTATIC study: a cluster
      randomised non-inferiority trial.
AB  - BACKGROUND: The use of cardiovascular medication for the primary prevention of
      cardiovascular disease (CVD) is potentially inappropriate when potential risks
      outweigh the potential benefits. It is unknown whether deprescribing preventive
      cardiovascular medication in patients without a strict indication for such
      medication is safe and cost-effective in general practice. METHODS: In this
      pragmatic cluster randomised controlled non-inferiority trial, we recruited 46
      general practices in the Netherlands. Patients aged 40-70 years who were using
      antihypertensive and/or lipid-lowering drugs without CVD and with low risk of
      future CVD were followed for 2 years. The intervention was an attempt to
      deprescribe preventive cardiovascular medication. The primary outcome was the
      difference in the increase in predicted (10-year) CVD risk in the per-protocol
      (PP) population with a non-inferiority margin of 2.5 percentage points. An
      economic evaluation was performed in the intention-to-treat (ITT) population. We
      used multilevel (generalised) linear regression with multiple imputation of
      missing data. RESULTS: Of 1067 participants recruited between 7 November 2012 and
      18 February 2014, 72% were female. Overall, their mean age was 55 years and their
      mean predicted CVD risk at baseline was 5%. Of 492 participants in the ITT
      intervention group, 319 (65%) quit the medication (PP intervention group); 135
      (27%) of those participants were still not taking medication after 2 years. The
      predicted CVD risk increased by 2.0 percentage points in the PP intervention
      group compared to 1.9 percentage points in the usual care group. The difference
      of 0.1 (95% CI -0.3 to 0.6) fell within the non-inferiority margin. After 2
      years, compared to the usual care group, for the PP intervention group, systolic
      blood pressure was 6 mmHg higher, diastolic blood pressure was 4 mmHg higher and
      total cholesterol and low-density lipoprotein-cholesterol levels were both 7
      mg/dl higher (all P < 0.05). Cost and quality-adjusted life years did not differ
      between the groups. CONCLUSIONS: The results of the ECSTATIC study show that an
      attempt to deprescribe preventive cardiovascular medication in low-CVD-risk
      patients is safe in the short term when blood pressure and cholesterol levels are
      monitored after stopping. An attempt to deprescribe medication can be considered,
      taking patient preferences into consideration. TRIAL REGISTRATION: This study was
      registered with Dutch trial register on 20 June 2012 ( NTR3493 ).

PMID- 29321032
TI  - Exploring the small-scale spatial distribution of hypertension and its
      association to area deprivation based on health insurance claims in Northeastern
      Germany.
AB  - BACKGROUND: Hypertension is one of the most frequently diagnosed chronic
      conditions in Germany. Targeted prevention strategies and allocation of general
      practitioners where they are needed most are necessary to prevent severe
      complications arising from high blood pressure. However, data on chronic diseases
      in Germany are mostly available through survey data, which do not only
      underestimate the actual prevalence but are also only available on coarse spatial
      scales. The discussion of including area deprivation for planning of healthcare
      is still relatively young in Germany, although previous studies have shown that
      area deprivation is associated with adverse health outcomes, irrespective of
      individual characteristics. The aim of this study is therefore to analyze the
      spatial distribution of hypertension at very fine geographic scales and to assess
      location-specific associations between hypertension, socio-demographic population
      characteristics and area deprivation based on health insurance claims of the AOK
      Nordost. METHODS: To visualize the spatial distribution of hypertension
      prevalence at very fine geographic scales, we used the conditional autoregressive
      Besag-York-Mollie (BYM) model. Geographically weighted regression modelling (GWR)
      was applied to analyze the location-specific association of hypertension to area
      deprivation and further socio-demographic population characteristics. RESULTS:
      The sex- and age-adjusted prevalence of hypertension was 33.1% in 2012 and varied
      widely across northeastern Germany. The main risk factors for hypertension were
      proportions of insurants aged 45-64, 65 and older, area deprivation and
      proportion of persons commuting to work outside their residential municipality.
      The GWR model revealed important regional variations in the strength of the
      examined associations. CONCLUSION: Area deprivation has only a significant and
      therefore direct influence in large parts of Mecklenburg-West Pomerania. However,
      the spatially varying strength of the association between demographic variables
      and hypertension indicates that there also exists an indirect effect of area
      deprivation on the prevalence of hypertension. It can therefore be expected that
      persons ageing in deprived areas will be at greater risk of hypertension,
      irrespective of their individual characteristics. The future planning and
      allocation of primary healthcare in northeastern Germany would therefore greatly
      benefit from considering the effect of area deprivation.

PMID- 29321033
TI  - Environmental enrichment intervention for Rett syndrome: an individually
      randomised stepped wedge trial.
AB  - BACKGROUND: Rett syndrome is caused by a pathogenic mutation in the MECP2 gene
      with major consequences for motor and cognitive development. One of the effects
      of impaired MECP2 function is reduced production of Brain Derived Neurotrophic
      Factor (BDNF), a protein required for normal neuronal development. When housed in
      an enriched environment, MECP2 null mice improved motor abilities and increased
      levels of BDNF in the brain. We investigated the effects of environmental
      enrichment on gross motor skills and blood BDNF levels in girls with Rett
      syndrome. METHODS: A genetically variable group of 12 girls with a MECP2 mutation
      and younger than 6 years participated in a modified individually randomised
      stepped wedge design study. Assessments were conducted on five occasions, two
      during the baseline period and three during the intervention period. Gross motor
      function was assessed using the Rett Syndrome Gross Motor Scale (maximum score of
      45) on five occasions, two during the baseline period and three during the
      intervention period. Blood levels of BDNF were measured at the two baseline
      assessments and at the end of the intervention period. The intervention comprised
      motor learning and exercise supplemented with social, cognitive and other sensory
      experiences over a six-month period. RESULTS: At the first assessment, the mean
      (SD) age of the children was 3 years (1 year 1 month) years ranging from 1 year 6
      months to 5 years 2 months. Also at baseline, mean (SD) gross motor scores and
      blood BDNF levels were 22.7/45 (9.6) and 165.0 (28.8) ng/ml respectively.
      Adjusting for covariates, the enriched environment was associated with improved
      gross motor skills (coefficient 8.2, 95%CI 5.1, 11.2) and a 321.4 ng/ml (95%CI
      272.0, 370.8) increase in blood BDNF levels after 6 months of treatment. Growth,
      sleep quality and mood were unaffected. CONCLUSIONS: Behavioural interventions
      such as environmental enrichment can reduce the functional deficit in Rett
      syndrome, contributing to the evidence-base for management and further
      understanding of epigenetic mechanisms. Environmental enrichment will be an
      important adjunct in the evaluation of new drug therapies that use BDNF pathways
      because of implications for the strengthening of synapses and improved
      functioning. TRIAL REGISTRATION: ACTRN12615001286538 .

PMID- 29321034
TI  - Diagnostic and prognostic utility of cardiovascular magnetic resonance imaging in
      heart failure with preserved ejection fraction - implications for clinical
      trials.
AB  - BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a poorly
      characterized condition. We aimed to phenotype patients with HFpEF using
      multiparametric stress cardiovascular magnetic resonance imaging (CMR) and to
      assess the relationship to clinical outcomes. METHODS: One hundred and fifty four
      patients (51% male, mean age 72 +/- 10 years) with a diagnosis of HFpEF underwent
      transthoracic echocardiography and CMR during a single study visit. The CMR
      protocol comprised cine, stress/rest perfusion and late gadolinium enhancement
      imaging on a 3T scanner. Follow-up outcome data (death and heart failure
      hospitalization) were captured after a minimum of 6 months. RESULTS: CMR detected
      previously undiagnosed pathology in 42 patients (27%), who had similar baseline
      characteristics to those without a new diagnosis. These diagnoses consisted of:
      coronary artery disease (n = 20, including 14 with 'silent' infarction),
      microvascular dysfunction (n = 11), probable or definite hypertrophic
      cardiomyopathy (n = 10) and constrictive pericarditis (n = 5). Four patients had
      dual pathology. During follow-up (median 623 days), patients with a new CMR
      diagnosis were at higher risk of adverse outcome for the composite endpoint (log
      rank test: p = 0.047). In multivariate Cox proportional hazards analysis, a new
      CMR diagnosis was the strongest independent predictor of adverse outcome (hazard
      ratio: 1.92; 95% CI: 1.07 to 3.45; p = 0.03). CONCLUSIONS: CMR diagnosed new
      significant pathology in 27% of patients with HFpEF. These patients were at
      increased risk of death and heart failure hospitalization. TRIAL REGISTRATION:
      ClinicalTrials.gov Identifier: NCT03050593 . Retrospectively registered; Date of
      registration: February 06, 2017.

PMID- 29321035
TI  - DHEA-induced ovarian hyperfibrosis is mediated by TGF-beta signaling pathway.
AB  - BACKGROUND: The polycystic ovary syndrome (PCOS) is a common metabolic and
      endocrine disorder with pathological mechanisms remain unclear. The following
      study investigates the ovarian hyperfibrosis forming via transforming growth
      factor-beta (TGF-beta) signaling pathway in Dehydroepiandrosterone (DHEA)-
      induced polycystic ovary syndrome (PCOS) rat model. We furthermore explored
      whether TGF-betaRI inhibitor (SB431542) decreases ovarian fibrosis by
      counterbalancing the expression of fibrotic biomarkers. METHODS: Thirty female
      Sprague-Dawley rats were randomly divided into Blank group (n = 6), Oil group (n
      = 6), and Oil + DHEA-induced model group (n = 6 + 12). The model groups were
      established by subcutaneous injection of DHEA for 35 consecutive days. The 12
      successful model rats were additionally divided in vehicle group (n = 6) and
      SB431542-treated group (n = 6). Vehicle group and SB431542-treated group, served
      as administration group and were intraperitoneally injected with DMSO and
      SB431542 for additional 14 consecutive days. Ovarian morphology, fibrin and
      collagen localization and expression in ovaries were detected using H&E staining,
      immunohistochemistry and Sirius red staining. The ovarian protein and RNA were
      examined using Western blot and RT-PCR. RESULTS: In DHEA-induced ovary in rat,
      fibrin and collagen had significantly higher levels, while the main fibrosis
      markers (TGF-beta, CTGF, fibronectin, a-SMA) were obviously upregulated. SB431542
      significantly reduced the expression of pro-fibrotic molecules (TGF-beta, Smad3,
      Smad2, a-SMA) and increased anti-fibrotic factor MMP2. CONCLUSION: TGF-betaRI
      inhibitor (SB431542) inhibits the downstream signaling molecules of TGF-beta and
      upregulates MMP2, which in turn prevent collagen deposition. Moreover, ovarian
      hyperfibrosis in DHEA-induced PCOS rat model could be improved by TGF-betaRI
      inhibitor (SB431542) restraining the transcription of accelerating fibrosis genes
      and modulating EMT mediator.

PMID- 29321037
TI  - Acute aortoiliac occlusive disease during percutaneous transluminal angioplasty
      in the setting of ST-elevation myocardial infarction: a case report.
AB  - BACKGROUND: Aortoiliac occlusive disease, which is also referred to as Leriche
      syndrome, is a chronic atherosclerotic occlusive disease that occurs at the level
      of the aortic bifurcation. It is often thought to present with a triad of
      clinical symptoms: (1) intermittent lower extremity vascular claudication, (2)
      impotence, and (3) weak/absent femoral pulses. CASE PRESENTATION: We report a
      case of a 47-year-old Caucasian woman who presented with an acute inferior ST
      elevation myocardial infarction. During percutaneous transluminal angioplasty,
      our patient suddenly developed severe bilateral lower extremity pain, absent
      femoral pulses, and cool extremities. Distal aortogram revealed 95% stenosis with
      an apple core-like lesion in the mid-abdominal aorta. Stent placement resulted in
      improved blood flow to the distal aortic segment and resolution of symptoms.
      CONCLUSIONS: The presence of significant peripheral vascular disease, significant
      cardiac risk factors, and/or difficulty accessing the femoral artery should
      caution a transfemoral approach during percutaneous transluminal angiography.
      This approach may precipitate aortoiliac occlusion and/or thromboembolism to the
      lower extremities. We encourage interventional cardiologists to (1) take extra
      caution when manipulating the wire and catheter and (2) strongly consider using a
      transradial approach in such patients.

PMID- 29321036
TI  - Maternal engineered nanomaterial inhalation during gestation alters the fetal
      transcriptome.
AB  - BACKGROUND: The integration of engineered nanomaterials (ENM) is well-established
      and widespread in clinical, commercial, and domestic applications. Cardiovascular
      dysfunctions have been reported in adult populations after exposure to a variety
      of ENM. As the diversity of these exposures continues to increase, the fetal
      ramifications of maternal exposures have yet to be determined. We, and others,
      have explored the consequences of ENM inhalation during gestation and identified
      many cardiovascular and metabolic outcomes in the F1 generation. The purpose of
      these studies was to identify genetic alterations in the F1 generation of Sprague
      Dawley rats that result from maternal ENM inhalation during gestation. Pregnant
      dams were exposed to nano-titanium dioxide (nano-TiO2) aerosols (10 +/- 0.5
      mg/m3) for 7-8 days (calculated, cumulative lung deposition = 217 +/- 1 MUg) and
      on GD (gestational day) 20 fetal hearts were isolated. DNA was extracted and
      immunoprecipitated with modified chromatin marks histone 3 lysine 4 tri
      methylation (H3K4me3) and histone 3 lysine 27 tri-methylation (H3K27me3).
      Following chromatin immunoprecipitation (ChIP), DNA fragments were sequenced. RNA
      from fetal hearts was purified and prepared for RNA sequencing and transcriptomic
      analysis. Ingenuity Pathway Analysis (IPA) was then used to identify pathways
      most modified by gestational ENM exposure. RESULTS: The results of the sequencing
      experiments provide initial evidence that significant epigenetic and
      transcriptomic changes occur in the cardiac tissue of maternal nano-TiO2 exposed
      progeny. The most notable alterations in major biologic systems included immune
      adaptation and organismal growth. Changes in normal physiology were linked with
      other tissues, including liver and kidneys. CONCLUSIONS: These results are the
      first evidence that maternal ENM inhalation impacts the fetal epigenome.

PMID- 29321038
TI  - Cross sectional study to assess the accuracy of electronic health record data to
      identify patients in need of lung cancer screening.
AB  - OBJECTIVE: Lung cancer is the leading cause of cancer death in the United States
      [Siegel et al. in CA Cancer J Clin 66:7-30, 1]. However, evidence from clinical
      trials indicates that annual low-dose computed tomography screening reduces lung
      cancer mortality [Humphrey et al. in Ann Intern Med 159:411-420, 2]. The
      objective of this study is to report results of a study designed to assess the
      sensitivity, specificity, and positive and negative predictive value of an
      electronic health record (EHR) query in comparison to patient self-report, to
      identify patients who may benefit from lung cancer screening. Cross sectional
      study comparing patient self report to EHR derived assessment of tobacco status
      and need for lung cancer screening. We invited 200 current or former smokers,
      ages 55-80 to complete a brief paper survey. 26 responded and 24 were included in
      the analysis. RESULTS: For 30% of respondents, there was not adequate EHR data to
      make a lung cancer screening determination. Compared to patient self-report, EHR
      derived data has a 67% sensitivity and 82% specificity for identifying patients
      that meet criteria for lung cancer screening. While the degree of accuracy may be
      insufficient to make a final lung cancer screening determination, EHR data may be
      useful in prompting clinicians to initiate conversations with patients in regards
      to lung cancer screening.

PMID- 29321039
TI  - Strategies to control HIV and HCV in methadone maintenance treatment in Guangdong
      Province, China: a system dynamic modeling study.
AB  - BACKGROUND: Human immunodeficiency virus (HIV) and hepatitis C virus (HCV)
      infections among methadone maintenance treatment (MMT) participants remain high.
      Optimized HIV and HCV prevention strategies for MMT clinics in resource-limited
      regions are urgently needed. This study aims to develop an MMT system dynamic
      model (SDM) to compare and optimize HIV and HCV control strategies in the MMT
      system. METHODS: We developed an MMT-SDM structure based on literature reviews.
      Model parameters were estimated from a cohort study, cross-sectional surveys and
      literature reviews. We further calibrated model outputs to historical data of HIV
      and HCV prevalence among MMT participants in 13 MMT clinics of Guangdong
      Province. Lastly, we simulated the impact of integrated interventions on HIV and
      HCV incidence among MMT participants using the MMT-SDM. RESULTS: The MMT-SDM
      comprises MMT clinics, MMT participants, detoxification centers, and HIV and HCV
      transmission, testing and treatment systems. We determined that condom promotion
      was the most effective way to reduce HIV infection (2013-2020: 2.86% to 1.76%) in
      MMT setting, followed by needle exchange program (2013-2020: 2.86% to 2.56%),
      psychological counseling (2013-2020: 2.86% to 2.71%) and contingency management
      (2013-2020: 2.86% to 2.72%). Health education had marginal impact on reducing HIV
      incidence among MMT participants (2013-2020:2.86% to 2.84%) from 2013 to 2020. By
      contrast, psychological counseling (2013-2020: 7.54% to 2.42%) and contingency
      management (2013-2020: 7.54% to 2.96%) had been shown to be the most effective
      interventions to reduce HCV incidence among MMT participants, followed by needle
      exchange program (2013-2020: 7.54% to 5.76%), health education (2013-2020: 7.54%
      to 6.35%), and condom promotion program (2013-2020: 7.54% to 6.40%). Notably, HCV
      treatment reduced HCV incidence by 0.32% (2013-2020: 7.54% to 7.22%).
      CONCLUSIONS: In conclusion, we generated a valuable system dynamic model to
      analyze the Chinese MMT system and to guide the decision-making process to
      further improve this system. This study underscores the importance of promoting
      condom use in MMT clinics and integrating psychosocial interventions to reduce
      HIV and HCV infections in MMT clinics in China.

PMID- 29321040
TI  - Automated image analysis detects aging in clinical-grade mesenchymal stromal cell
      cultures.
AB  - BACKGROUND: Senescent cells are undesirable in cell therapy products due to
      reduced therapeutic activity and risk of aberrant cellular effects, and methods
      for assessing senescence are needed. Early-passage mesenchymal stromal cells
      (MSCs) are known to be small and spindle-shaped but become enlarged upon cell
      aging. Indeed, cell morphology is routinely evaluated during MSC production using
      subjective methods. We have therefore explored the possibility of utilizing
      automated imaging-based analysis of cell morphology in clinical cell
      manufacturing. METHODS: An imaging system was adopted for analyzing changes in
      cell morphology of bone marrow-derived MSCs during long-term culture. Cells taken
      from the cultures at the desired passages were plated at low density for imaging,
      representing morphological changes observed in the clinical-grade cultures. The
      manifestations of aging and onset of senescence were monitored by population
      doubling numbers, expression of p16INK4a and p21Cip1/Waf1, beta-galactosidase
      activity, and telomeric terminal restriction fragment analysis. RESULTS: Cell
      area was the most statistically significant and practical parameter for
      describing morphological changes, correlating with biochemical senescence
      markers. MSCs from passages 1 (p1) and 3 (p3) were remarkably uniform in size,
      with cell areas between 1800 and 2500 MUm2. At p5 the cells began to enlarge
      resulting in a 4.8-fold increase at p6-9 as compared to p1. The expression of
      p16INK4a and activity of beta-galactosidase had a strong correlation with the
      increase in cell area, whereas the expression of p21Cip1/Waf1 reached its maximum
      at the onset of growth arrest and subsequently decreased. Mean telomere length
      shortened at an apparently constant rate during culture, from 8.2 +/- 0.3 kbp at
      p1, reaching 6.08 +/- 0.6 kbp at senescence. CONCLUSIONS: Imaging analysis of
      cell morphology is a useful tool for evaluating aging in cell cultures throughout
      the lifespan of MSCs. Our findings suggest that imaging analysis can reproducibly
      detect aging-related changes in cell morphology in MSC cultures. These findings
      suggest that cell morphology is still a supreme measure of cell quality and may
      be utilized to develop new noninvasive imaging-based methods to screen and
      quantitate aging in clinical-grade cell cultures.

PMID- 29321041
TI  - Effects of stress ulcer prophylaxis in adult ICU patients receiving renal
      replacement therapy (Sup-Icu RENal, SIREN): Study protocol for a pre-planned
      observational study.
AB  - BACKGROUND: Proton pump inhibitors are often used in critically ill patients to
      prevent gastrointestinal bleeding despite limited evidence for benefit. Patients
      with acute kidney injury requiring renal replacement therapy (RRT) are at high
      risk of gastrointestinal bleeding as (pre-)uremia induces coagulopathy through
      effects on platelets and coagulation cascades. No high-quality randomized
      clinical trials have previously assessed the benefits and harms of prophylactic
      proton pump inhibitor use in this high-risk population of adult critically ill
      patients. METHODS/DESIGN: Among the 3350 patients included in the Stress Ulcer
      Prophylaxis in the Intensive Care Unit (SUP-ICU) trial-an investigator-initiated
      international randomized clinical trial on prophylactic proton pump inhibitor
      versus placebo in acutely admitted adult ICU patients at risk of gastrointestinal
      bleeding-we will compare the benefits and harms of prophylactic use of proton
      pump inhibitor in patients in need of RRT versus those not requiring this
      treatment. We will determine the proportion of patients with clinically important
      bleeding, the proportion of patients with adverse events including pneumonia,
      Clostridium difficile enteritis, or acute myocardial ischemia in the ICU, as well
      as transfusion requirements. Moreover, 90 day and 365 day mortality post
      randomization will be investigated. As a secondary analysis, we will examine the
      association between acute kidney injury and RRT during ICU stay and
      gastrointestinal bleeding. DISCUSSION: With the outlined predefined analysis, we
      will characterize the balance between the benefits and harms of stress ulcer
      prophylaxis in acutely admitted adult ICU patients in need of RRT, including the
      potential interaction of allocation to proton pump inhibitor versus placebo.
      TRIAL REGISTRATION: ClinicalTrials.gov, NCT02718261 . Registered on 14 March
      2016.

PMID- 29321042
TI  - Type I IFN signature in childhood-onset systemic lupus erythematosus: a
      conspiracy of DNA- and RNA-sensing receptors?
AB  - BACKGROUND: Childhood-onset systemic lupus erythematosus (cSLE) is an incurable
      multi-systemic autoimmune disease. Interferon type I (IFN-I) plays a pivotal role
      in the pathogenesis of SLE. The objective of this study was to assess the
      prevalence of the IFN-I signature and the contribution of cytosolic nucleic acid
      receptors to IFN-I activation in a cohort of primarily white cSLE patients.
      METHODS: The IFN-I score (positive or negative), as a measure of IFN-I
      activation, was assessed using real-time quantitative PCR (RT-PCR) expression
      values of IFN-I signature genes (IFI44, IFI44L, IFIT1, Ly6e, MxA, IFITM1) in
      CD14+ monocytes of cSLE patients and healthy controls (HCs). Innate immune
      receptor expression was determined by RT-PCR and flow cytometry. To clarify the
      contribution of RNA-binding RIG-like receptors (RLRs) and DNA-binding receptors
      (DBRs) to IFN-I activation, peripheral blood mononuclear cells (PBMCs) from
      patients were treated with BX795, a TANK-binding kinase 1 (TBK1) inhibitor
      blocking RLR and DBR pathways. RESULTS: The IFN-I signature was positive in 57%
      of cSLE patients and 15% of the HCs. Upregulated gene expression of TLR7, RLRs
      (IFIH1, DDX58, DDX60, DHX58) and DBRs (ZBP-1, IFI16) was observed in CD14+
      monocytes of the IFN-I-positive cSLE patients. Additionally, RIG-I and ZBP-1
      protein expression was upregulated in these cells. Spontaneous IFN-I stimulated
      gene (ISG) expression in PBMCs from cSLE patients was inhibited by a TBK1
      blocker. CONCLUSIONS: IFN-I activation, assessed as ISG expression, in cSLE is
      associated with increased expression of TLR7, and RNA and DNA binding receptors,
      and these receptors contribute to IFN-I activation via TBK1 signaling. TBK1
      blockers may therefore be a promising treatment target for SLE.

PMID- 29321044
TI  - Three unreported cases of TMEM199-CDG, a rare genetic liver disease with abnormal
      glycosylation.
AB  - BACKGROUND: TMEM199 deficiency was recently shown in four patients to cause liver
      disease with steatosis, elevated serum transaminases, cholesterol and alkaline
      phosphatase and abnormal protein glycosylation. There is no information on the
      long-term outcome in this disorder. RESULTS: We here present three novel patients
      with TMEM199-CDG. All three patients carried the same set of mutations (c.13
      14delTT (p.Ser4Serfs*30) and c.92G > C (p.Arg31Pro), despite only two were
      related (siblings). One mutation (c.92G > C) was described previously whereas the
      other was deemed pathogenic due to its early frameshift. Western Blot analysis
      confirmed a reduced level of TMEM199 protein in patient fibroblasts and all
      patients showed a similar glycosylation defect. The patients presented with a
      very similar clinical and biochemical phenotype to the initial publication,
      confirming that TMEM199-CDG is a non-encephalopathic liver disorder. Two of the
      patients were clinically assessed over two decades without deterioration.
      CONCLUSION: A rising number of disorders affecting Golgi homeostasis have been
      published over the last few years. A hallmark finding is deficiency in protein
      glycosylation, both in N- and O-linked types. Most of these disorders have signs
      of both liver and brain involvement. However, the present and the four previously
      reported patients do not show encephalopathy but a chronic, non-progressive (over
      decades) liver disease with hypertransaminasemia and steatosis. This information
      is crucial for the patient/families and clinician at diagnosis, as it
      distinguishes it from other Golgi homeostasis disorders, in having a much more
      favorable course.

PMID- 29321043
TI  - What is in your wallet? A cluster randomized trial of the effects of showing
      comparative patient out-of-pocket costs on primary care prescribing for
      uncomplicated hypertension.
AB  - BACKGROUND: Drug expenditures are responsible for an increasing proportion of
      health costs, accounting for $1.1 trillion in annual expenditure worldwide. As
      hundreds of billions of dollars are being spent each year on overtreatment with
      prescribed medications that are either unnecessary or are in excess of lowest
      cost-effective therapy, programs are needed that optimize fiscally appropriate
      use. We evaluated whether providing physicians with information on the patient
      out-of-pocket payment consequences of prescribing decisions that were in excess
      of lowest cost-effective therapy would alter prescribing decisions using the
      treatment of uncomplicated hypertension as an exemplar. METHODS: A single-blind
      cluster randomized trial was conducted over a 60-month follow-up period in 76
      primary care physicians in Quebec, Canada, and their patients with uncomplicated
      hypertension who were using the MOXXI integrated electronic health record for
      drug and health problem management. Physicians were randomized to an out-of
      pocket expenditure module that provided alerts for comparative out-of-payment
      costs, thiazide diuretics as recommended first-line therapy, and tools to monitor
      blood pressure targets and medication compliance, or alternatively the basic
      MOXXI system. System software and prescription claims were used to analyze the
      impact of the intervention on treatment choice, adherence, and overall and out-of
      pocket payment costs using generalized estimating equations. RESULTS: Three
      thousand five-hundred ninety-two eligible patients with uncomplicated
      hypertension were enrolled, of whom 1261 (35.1%) were newly started (incident
      patient) on treatment during follow-up. There was a statistically significant
      increase in the prescription of diuretics in the newly treated intervention
      (26.6%) compared to control patients (19.8%) (RR 1.65, 95% CI 1.17 to 2.33). For
      patients already treated (prevalent patient), there was a statistically
      significant interaction between the intervention and patient age, with older
      patients being less likely to be switched to a diuretic. Among the incident
      patients, physicians with less than 15 years of experience were much more likely
      to prescribe a diuretic (OR 10.69; 95% CI 1.49 to 76.64) than physicians with 15
      to 25 years (OR 0.67; 95%CI 0.25 to 1.78), or more than 25 years of experience
      (OR 1.80; 95% CI 1.23 to 2.65). There was no statistically significant effect of
      the intervention on adherence or out-of-pocket payment cost. CONCLUSIONS: The
      provision of comparative information on patient out-of-pocket payments for
      treatment of uncomplicated hypertension had a statistically significant impact on
      increasing the initiation of diuretics in incident patients and switching to
      diuretics in younger prevalent patients. The impact of interventions to improve
      the cost-effectiveness of prescribing may be enhanced by also targeting patients
      with tools to participate in treatment decision-making and by providing
      physicians with comparative out-of-pocket information on all evidence-based
      alternatives that would enhance clinical decision-making. TRIAL REGISTRATION:
      ISRCTN96253624.

PMID- 29321045
TI  - Stem cells and anti-aging genes: double-edged sword-do the same job of life
      extension.
AB  - Aging impacts diseases and lifespan. With current knowledge of stem cells, it is
      feasible to design and test interventions that delay aging and improve both
      health and lifespan. Stem cells, together with anti-aging genes such as Klotho,
      play a crucial role in delaying the aging process. Stem cells in combination with
      anti-aging genes make a complex and protective shield, which stand against the
      eroding effects of aging. Increased wear and tear of the stem cells, as well as
      Klotho deficiency, is expected to heavily increase cellular damage and accelerate
      the process of aging. Stem cells in conjugation with anti-aging genes probably
      receive and neutralize most of the devastating signaling effects which are known
      to cause premature aging. The shield of stem cells combined with anti-aging genes
      is a primary target for absorbing the shock of aging. If this shield neutralizes
      the shocks, it could lead to a youthful state, but if not it will accelerate the
      aging journey. In this review, we concisely discuss the neutralizing ability,
      operated and regulated by stem cells and other life-extension factors. We suggest
      that stem cell interventions that increase rejuvenation and keep in balance the
      expression of anti-aging genes could delay the aging phenotypes and result in
      prolonged lifespan.

PMID- 29321046
TI  - Application of causal inference methods in the analyses of randomised controlled
      trials: a systematic review.
AB  - BACKGROUND: Applications of causal inference methods to randomised controlled
      trial (RCT) data have usually focused on adjusting for compliance with the
      randomised intervention rather than on using RCT data to address other, non
      randomised questions. In this paper we review use of causal inference methods to
      assess the impact of aspects of patient management other than the randomised
      intervention in RCTs. METHODS: We identified papers that used causal inference
      methodology in RCT data from Medline, Premedline, Embase, Cochrane Library, and
      Web of Science from 1986 to September 2014, using a forward citation search of
      five seminal papers, and a keyword search. We did not include studies where
      inverse probability weighting was used solely to balance baseline
      characteristics, adjust for loss to follow-up or adjust for non-compliance to
      randomised treatment. Studies where the exposure could not be assigned were also
      excluded. RESULTS: There were 25 papers identified. Nearly half the papers
      (11/25) estimated the causal effect of concomitant medication on outcome. The
      remainder were concerned with post-randomisation treatment regimens (sequential
      treatments, n =5 ), effects of treatment timing (n = 2) and treatment dosing or
      duration (n = 7). Examples were found in cardiovascular disease (n = 5), HIV (n =
      7), cancer (n = 6), mental health (n = 4), paediatrics (n = 2) and transfusion
      medicine (n = 1). The most common method implemented was a marginal structural
      model with inverse probability of treatment weighting. CONCLUSIONS: Examples of
      studies which exploit RCT data to address non-randomised questions using causal
      inference methodology remain relatively limited, despite the growth in
      methodological development and increasing utilisation in observational studies.
      Further efforts may be needed to promote use of causal methods to address
      additional clinical questions within RCTs to maximise their value.

PMID- 29321048
TI  - Danish first aid books compliance with the new evidence-based non-resuscitative
      first aid guidelines.
AB  - BACKGROUND: The European Resuscitation Council (ERC) released new guidelines on
      resuscitation in 2015. For the first time, the guidelines included a separate
      chapter on first aid for laypersons. We analysed the current major Danish
      national first aid books to identify potential inconsistencies between the
      current books and the new evidence-based first aid guidelines. METHODS: We
      identified first aid books from all the first aid courses offered by major Danish
      suppliers. Based on the new ERC first aid guidelines, we developed a checklist of
      26 items within 16 different categories to assess the content; this checklist was
      adapted following the principle of mutually exclusive and collectively exhaustive
      questioning. To assess the agreement between four raters, Fleiss' kappa test was
      used. Items that did not reach an acceptable kappa score were excluded. RESULTS:
      We evaluated 10 first aid books used for first aid courses and published between
      2009 and 2015. The content of the books complied with the new in 38% of the
      answers. In 12 of the 26 items, there was less than 50% consistency. These items
      include proximal pressure points and elevation of extremities for the control of
      bleeding, use of cervical collars, treatment for an open chest wound, burn
      dressing, dental avulsion, passive leg raising, administration of
      bronchodilators, adrenaline, and aspirin. CONCLUSIONS: Danish course material
      showed significant inconsistencies with the new evidence-based first aid
      guidelines. The new knowledge from the evidence-based guidelines should be
      incorporated into revised and updated first aid course material.

PMID- 29321047
TI  - Effects of concentrated long-chain omega-3 polyunsaturated fatty acid
      supplementation before radical prostatectomy on prostate cancer proliferation,
      inflammation, and quality of life: study protocol for a phase IIb, randomized,
      double-blind, placebo-controlled trial.
AB  - BACKGROUND: Prostate cancer is the most commonly diagnosed cancer in north
      American men. Few dietary or lifestyle interventions have been tested to prevent
      prostate cancer progression. Omega-3 fatty acid supplementation represents a
      promising intervention for prostate cancer patients. The aim of the study is to
      evaluate the effects of long-chain omega-3 polyunsaturated fatty acids (LCn3),
      more precisely eicosapentaenoic acid monoacylglyceride (MAG-EPA) supplementation,
      on prostate cancer proliferation, inflammation mediators and quality of life
      among men who will undergo radical prostatectomy. METHODS/DESIGN: We propose a
      phase IIb, randomized, double-blind placebo-controlled trial of MAG-EPA
      supplementation for 130 men who will undergo radical prostatectomy as treatment
      for a prostate cancer of Gleason score >= 7 in an academic cancer center in
      Quebec City. Participants will be randomized to 6 capsules of 625 mg of fish oil
      (MAG-EPA) per capsule containing 500 mg of EPA daily or to identically looking
      capsules of high oleic acid sunflower oil (HOSO) as placebo. The intervention
      begins 4 to 10 weeks prior to radical prostatectomy (baseline) and continues for
      one year after surgery. The primary endpoint is the proliferative index (Ki-67)
      measured in prostate cancer cells at radical prostatectomy. A secondary endpoint
      includes prostate tissue levels of inflammatory mediators (cytokines and
      proteins) at time of radical prostatectomy. Changes in blood levels of
      inflammatory mediators, relative to baseline levels, at time of radical
      prostatectomy and 12 months after radical prostatectomy will also be evaluated.
      Secondary endpoints also include important aspects of psychosocial functioning
      and quality of life such as depression, anxiety, sleep disturbances, fatigue,
      cognitive complaints and prostate cancer-specific quality of life domains. The
      changes in these outcomes, relative to baseline levels, will be evaluated at 3,
      6, 9 and 12 months after radical prostatectomy. DISCUSSION: The results from this
      trial will provide crucial information to clarify the role of omega-3
      supplementation on prostate cancer proliferation, inflammation and quality of
      life. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02333435. Registered
      on December 17, 2014. Last updated September 6, 2016.

PMID- 29321049
TI  - Human liver organoids generated with single donor-derived multiple cells rescue
      mice from acute liver failure.
AB  - BACKGROUND: Acute liver failure (ALF) is a life-threatening disease with a high
      mortality rate. However, there are limited treatments or devices available for
      ALF therapy. Here, we aimed to develop a new strategy for ALF treatment by
      transplanting functional liver organoids (LOs) generated from single donor
      derived human induced pluripotent stem cell (hiPSC) endoderm, endothelial cells
      (ECs), and mesenchymal cells (MCs). METHODS: First, we isolated ECs and MCs from
      a single donor umbilical cord (UC) through enzyme digestion and characterized the
      UC-ECs and UC-MCs by flow cytometry. Second, using a nonviral reprogramming
      method, we generated same donor-derived hiPSCs from the UC-ECs and investigated
      their hepatic differentiation abilities. Finally, we simultaneously plated EC
      hiPSC endoderm, UC-ECs, and UC-MCs in a three-dimensional (3D) microwell culture
      system, and generated single donor cell-derived differentiated LOs for ALF mouse
      treatment. RESULTS: We obtained ECs and MCs from a single donor UC with high
      purity, and these cells provided a multicellular microenvironment that promoted
      LO differentiation. hiPSCs from the same donor were generated from UC-ECs, and
      the resultant EC-hiPSCs could be differentiated efficiently into pure definitive
      endoderm and further into hepatic lineages. Simultaneous plating of EC-hiPSC
      endoderm, UC-ECs, and UC-MCs in the 3D microwell system generated single donor
      cell-derived LOs (SDC-LOs) that could be differentiated into functional LOs with
      enhanced hepatic capacity as compared to that of EC-hiPSC-derived hepatic-like
      cells. When these functional SDC-LOs were transplanted into the renal subcapsules
      of ALF mice, they rapidly assumed hepatic functions and improved the survival
      rate of ALF mice. CONCLUSION: These results demonstrate that functional LOs
      generated from single donor cells can improve the condition of ALF mice.
      Functional SDC-LO transplantation provides a promising novel approach for ALF
      therapy.

PMID- 29321050
TI  - Plasminogen activator inhibitor-1: a risk factor for deep vein thrombosis after
      total hip arthroplasty.
AB  - BACKGROUND: The onset of deep vein thrombosis (DVT) in patients after total hip
      arthroplasty (THA) may expand or enlarge and subsequently lead to significant
      mortality. The objective of this study was to investigate potential risk factors
      for DVT in patients after THA. METHODS: Eligible patients with hip joint diseases
      who were scheduled for unilateral primary THA at our hospital were prospectively
      included into this study. The demographic and clinical features, preoperative
      plasma biomarkers were detailed, recorded, and compared. The multiple logistic
      regression analysis was used to evaluate potential risk factors for DVT. RESULTS:
      A total of 214 subjects were enrolled into our study cohort for the final
      analysis, and 23 of them have suffered DVT with an incidence of 9.5%. The
      performance of logistic regression analysis showed that preoperative expression
      of plasminogen activator inhibitor-1 (PAI-1) was an independent risk factor for
      the onset of DVT in patients after THA (OR 1.18, 95% CI 1.04-1.29; p = 0.011).
      CONCLUSIONS: Our study indicated preoperative plasma PAI-1 expression as an
      independent risk factor for DVT in patients who underwent THA.

PMID- 29321051
TI  - Midwives' respect and disrespect of women during facility-based childbirth in
      urban Tanzania: a qualitative study.
AB  - BACKGROUND: Over the last two decades, facility-based childbirths in Tanzania
      have only minimally increased by 10% partly because of healthcare providers'
      disrespect and abuse (D&A) of women during childbirth. Although numerous studies
      have substantiated women's experience of D&A during childbirth by healthcare
      providers, few have focused on how D&A occurred during the midwives' actual care.
      This study aimed to describe from actual observations the respectful and
      disrespectful care received by women from midwives during their labor period in
      two hospitals in urban Tanzania. METHODS: This descriptive qualitative study
      involved naturalistic observation of two health facilities in urban Tanzania.
      Fourteen midwives were purposively recruited for the one-on-one shadowing of
      their care of 24 women in labor from admission to the fourth stage of labor.
      Observations of their midwifery care were analyzed using content analysis.
      RESULTS: All the 14 midwives showed both respectful and disrespectful care and
      some practices that have not been explicated in previous reports of women's
      experiences. For respectful care, five categories were identified: 1) positive
      interactions between midwives and women, 2) respect for women's privacy, 3)
      provision of safe and timely midwifery care for delivery, 4) active engagement in
      women's labor process, and 5) encouragement of the mother-baby relationship. For
      disrespectful care, five categories were recognized: 1) physical abuse, 2)
      psychological abuse, 3) non-confidential care, 4) non-consented care, and 5)
      abandonment of care. Two additional categories emerged from the unprioritized and
      disorganized nursing and midwifery management: 1) lack of accountability and 2)
      unethical clinical practices. CONCLUSIONS: Both respectful care and disrespectful
      care of midwives were observed in the two health facilities in urban Tanzania.
      Several types of physical and psychological abuse that have not been reported
      were observed. Weak nursing and midwifery management was found to be a
      contributor to the D&A of women. To promote respectful care of women, pre-service
      and in-service trainings, improvement of working conditions and environment,
      empowering pregnant women, and strengthening health policies are crucial.

PMID- 29321052
TI  - ASGDB: a specialised genomic resource for interpreting Anopheles sinensis
      insecticide resistance.
AB  - BACKGROUND: Anopheles sinensis is an important malaria vector in Southeast Asia.
      The widespread emergence of insecticide resistance in this mosquito species poses
      a serious threat to the efficacy of malaria control measures, particularly in
      China. Recently, the whole-genome sequencing and de novo assembly of An. sinensis
      (China strain) has been finished. A series of insecticide-resistant studies in
      An. sinensis have also been reported. There is a growing need to integrate these
      valuable data to provide a comprehensive database for further studies on
      insecticide-resistant management of An. sinensis. RESULTS: A bioinformatics
      database named An. sinensis genome database (ASGDB) was built. In addition to
      being a searchable database of published An. sinensis genome sequences and
      annotation, ASGDB provides in-depth analytical platforms for further
      understanding of the genomic and genetic data, including visualization of genomic
      data, orthologous relationship analysis, GO analysis, pathway analysis,
      expression analysis and resistance-related gene analysis. Moreover, ASGDB
      provides a panoramic view of insecticide resistance studies in An. sinensis in
      China. In total, 551 insecticide-resistant phenotypic and genotypic reports on
      An. sinensis distributed in Chinese malaria-endemic areas since the mid-1980s
      have been collected, manually edited in the same format and integrated into
      OpenLayers map-based interface, which allows the international community to
      assess and exploit the high volume of scattered data much easier. The database
      has been given the URL: http://www.asgdb.org /. CONCLUSIONS: ASGDB was built to
      help users mine data from the genome sequence of An. sinensis easily and
      effectively, especially with its advantages in insecticide resistance
      surveillance and control.

PMID- 29321053
TI  - Data sharing in clinical trials - practical guidance on anonymising trial
      datasets.
AB  - BACKGROUND: There is an increasing demand by non-commercial funders that
      trialists should provide access to trial data once the primary analysis is
      completed. This has to take into account concerns about identifying individual
      trial participants, and the legal and regulatory requirements. METHODS: Using the
      good practice guideline laid out by the work funded by the Medical Research
      Council Hubs for Trials Methodology Research (MRC HTMR), we anonymised a dataset
      from a recently completed trial. Using this example, we present practical
      guidance on how to anonymise a dataset, and describe rules that could be used on
      other trial datasets. We describe how these might differ if the trial was to be
      made freely available to all, or if the data could only be accessed with specific
      permission and data usage agreements in place. RESULTS: Following the good
      practice guidelines, we successfully created a controlled access model for trial
      data sharing. The data were assessed on a case-by-case basis classifying
      variables as direct, indirect and superfluous identifiers with differing methods
      of anonymisation assigned depending on the type of identifier. A final dataset
      was created and checks of the anonymised dataset were applied. Lastly, a
      procedure for release of the data was implemented to complete the process.
      CONCLUSIONS: We have implemented a practical solution to the data anonymisation
      process resulting in a bespoke anonymised dataset for a recently completed trial.
      We have gained useful learnings in terms of efficiency of the process going
      forward, the need to balance anonymity with data utilisation and future work that
      should be undertaken.

PMID- 29321054
TI  - The association between daily concentrations of air pollution and visits to a
      psychiatric emergency unit: a case-crossover study.
AB  - BACKGROUND: Air pollution is one of the leading causes of mortality and morbidity
      worldwide. Experimental studies, and a few epidemiological studies, suggest that
      air pollution may cause acute exacerbation of psychiatric disorders, and even
      increase the rate of suicide attempts, but epidemiological studies on air
      pollution in association with psychiatric disorders are still few. Our aim was to
      investigate associations between daily fluctuations in air pollution
      concentrations and the daily number of visits to a psychiatric emergency unit.
      METHODS: Data from Sahlgrenska University Hospital, Gothenburg, Sweden, on the
      daily number of visits to the Psychiatric emergency unit were combined with daily
      data on monitored concentrations of respirable particulate matter(PM10),
      ozone(O3), nitrogen dioxides(NO2) and temperature between 1st July 2012 and 31st
      December 2016. We used a case-crossover design to analyze data with conditional
      Poisson regression models allowing for over-dispersion. We stratified data on
      season. RESULTS: Visits increased with increasing PM10 levels during the warmer
      season (April to September) in both single-pollutant and two-pollutant models.
      For example, an increase of 3.6% (95% Confidence Interval, CI, 0.4-7.0%) was
      observed with a 10 MUg/m3 increase in PM10 adjusted for NO2. In the three
      pollutant models (adjusting for NO2 and O3 simultaneously) the increase was 3.3%
      (95% CI, -0.2-6.9). There were no clear associations between the outcome and NO2,
      O3, or PM10 during the colder season (October to March). CONCLUSIONS: Ambient air
      particle concentrations were associated with the number of visits to the
      Psychiatric emergency unit in the warm season. The results were only borderline
      statistically significant in the fully adjusted (three-pollutant) models in this
      small study. The observation could be interpreted as indicative of air pollution
      as either exacerbating an underlying psychiatric disorder, or increasing mental
      distress, even in areas with comparatively low levels of air pollution. In
      combination with the severe impact of psychiatric disorders and mental distress
      on society and individuals, our results are a strong warrant for future research
      in this area.

PMID- 29321056
TI  - MRI appearance of ovarian serous borderline tumors of the micropapillary type
      compared to that of typical ovarian serous borderline tumors: radiologic
      pathologic correlation.
AB  - BACKGROUND: Serous borderline tumor (SBT) of the micropapillary type (SBT-MP)
      became one of the major pathological SBT diagnoses in addition to typical SBT,
      and was also defined as "non-invasive" low-gradeserous carcinoma according to the
      World Health Organization (WHO) classification in 2014. In this study, we
      investigated the MRI appearance of SBT-MP compared to that of typical SBT in
      order to identify specific imaging features of SBT-MP that correspond to
      pathological findings. METHODS: MR images of 6 histologically proven ovarian SBT
      MP in four patients and 14 typical SBT in ten patients were reviewed
      retrospectively. Images were evaluated for laterality, size and morphology of the
      lesion and the solid component (SC) and signal intensity (SI) of the SC. MRI
      findings were correlated with pathological findings. RESULTS: The patients with
      SBT-MP (mean 26.3 years) were younger than those with typical SBT (mean 44.5
      years). Postoperative staging in patients with SBT-MP was II in two and III in
      two cases, while staging for typical SBT was I in seven, II in one and III in two
      cases. The morphologic patterns of SBT-MP were a unilateral cystic mass with
      intracystic mural nodules (CwMN) (n = 2), bilateral solid papillary masses (SM),
      and bilateral SM with CwMN. The pattern of typical SBT was CwMN (n = 13) in all
      but one lesion (SM with CwMN). All SCs showed inhomogeneous slight hyperintensity
      on T2 weighted images (WI) and high SI on diffusion-WI (DWI) except for in one
      typical SBT. Although diffuse proliferation of the tumor cells in micropapillary
      projections with little stroma seemed to correspond to inhomogeneous slightly
      hyperintense foci in SC on T2WI and high SI on DWI, similar MR findings were
      observed in typical SBT in all lesions on T2WI and 11 of 12 lesions on DWI. In
      typical SBT, inhomogeneous slightly hyperintense foci in SC on T2WI and high SI
      on DWI corresponded to highly cellular foci with densely branched papillae.
      CONCLUSION: Pathological findings and clinical behavior of SBT-MP differed from
      those of typical SBT, but morphology and SI of SC on MRI were similar, with
      papillary projections demonstrating inhomogeneous slight hyperintensity on T2WI
      and high SI on DWI.

PMID- 29321055
TI  - Trends and correlates of overweight/obesity in Czech adolescents in relation to
      family socioeconomic status over a 12-year study period (2002-2014).
AB  - BACKGROUND: This study examined a) trends in overweight/obesity, moderate-to
      vigorous physical activity (MVPA), and screen time (ST) among Czech adolescents
      over a 12-year study period (2002-2014) in relation to family affluence (FA) and
      b) correlates of adolescent overweight/obesity from different FA categories.
      METHODS: A nationally representative sample of 18,250 adolescents (51.4% girls)
      aged 10.5-16.5 years was drawn from the Czech Health Behaviour in School-aged
      Children questionnaire-based surveys in 2002, 2006, 2010, and 2014. Using the FA
      scale, the socioeconomic status (SES) of the respondents' families was assessed.
      SES-stratified trends in the prevalence of overweight/obesity meeting the MVPA
      (>=60 min/day), and ST (<=2 h/day) recommendations were assessed using logistic
      regression. RESULTS: A trend-related significant increase (p < 0.05) in the
      prevalence of overweight/obesity was observed in low-/medium-FA boys and medium
      /high-FA girls. Unlike in high-FA adolescents, a significant decrease was
      revealed in the rates of meeting the MVPA recommendation in low-FA boys
      (28.9%2002 -> 23.3%2014, OR = 0.75, 95% CI = 0.59-0.95, p < 0.05) and girls
      (22.3%2002 -> 17.3%2014, OR = 0.73, 95% CI = 0.57-0.92, p < 0.01). A significant
      (p < 0.001) trend-related increase in excessive ST was evident in adolescents
      regardless of gender and FA category. Generally, girls and older adolescents had
      lower odds of overweight/obesity than boys and 11-year-old adolescents. While in
      the high-FA category of adolescents, achieving 60 min of MVPA daily and the
      absence of excessive ST on weekdays significantly (p < 0.01) reduced their odds
      of being overweight/obese, in low-FA adolescents this was not the case.
      CONCLUSIONS: High rates of overweight/obesity and a poor level of daily MVPA
      among low-FA children provide disturbing evidence highlighting the necessity of
      public health efforts to implement obesity reduction interventions for this
      disadvantaged population.

PMID- 29321057
TI  - Influenza A virus infection impacts systemic microbiota dynamics and causes
      quantitative enteric dysbiosis.
AB  - BACKGROUND: Microbiota integrity is essential for a growing number of
      physiological processes. Consequently, disruption of microbiota homeostasis
      correlates with a variety of pathological states. Importantly, commensal
      microbiota provide a shield against invading bacterial pathogens, probably by
      direct competition. The impact of viral infections on host microbiota composition
      and dynamics is poorly understood. Influenza A viruses (IAV) are common
      respiratory pathogens causing acute infections. Here, we show dynamic changes in
      respiratory and intestinal microbiota over the course of a sublethal IAV
      infection in a mouse model. RESULTS: Using a combination of 16S rRNA gene
      specific next generation sequencing and qPCR as well as culturing of bacterial
      organ content, we found body site-specific and transient microbiota responses. In
      the lower respiratory tract, we observed only minor qualitative changes in
      microbiota composition. No quantitative impact on bacterial colonization after
      IAV infection was detectable, despite a robust antimicrobial host response and
      increased sensitivity to bacterial super infection. In contrast, in the
      intestine, IAV induced robust depletion of bacterial content, disruption of mucus
      layer integrity, and higher levels of antimicrobial peptides in Paneth cells. As
      a functional consequence of IAV-mediated microbiota depletion, we demonstrated
      that the small intestine is rendered more susceptible to bacterial pathogen
      invasion, in a Salmonella typhimurium super infection model. CONCLUSION: We show
      for the first time the consequences of IAV infection for lower respiratory tract
      and intestinal microbiobiota in a qualitative and quantitative fashion. The
      discrepancy of relative 16S rRNA gene next-generation sequencing (NGS) and
      normalized 16S rRNA gene-specific qPCR stresses the importance of combining
      qualitative and quantitative approaches to correctly analyze composition of organ
      associated microbial communities. The transiently induced dysbiosis underlines
      the overall stability of microbial communities to effects of acute infection.
      However, during a short-time window, specific ecological niches might lose their
      microbiota shield and remain vulnerable to bacterial invasion.

PMID- 29321059
TI  - Intrarater reliability of the Humac NORM isokinetic dynamometer for strength
      measurements of the knee and shoulder muscles.
AB  - OBJECTIVE: To determine the intrarater reliability of the Humac NORM isokinetic
      dynamometer for concentric and eccentric strength tests of knee and shoulder
      muscles. RESULTS: 54 participants (50% female, average age 20.9 +/- 3.1 years)
      performed concentric and eccentric strength measures of the knee extensors and
      flexors, and the shoulder internal and external rotators on two different Humac
      NORM isokinetic dynamometers, which were situated at two different centers. The
      knee extensors and flexors were tested concentrically at 60 degrees  and 180
      degrees /s, and eccentrically at 60 degrees  s. Concentric strength of the
      shoulder internal and external rotators, and eccentric strength of the external
      rotators were measured at 60 degrees  and 120 degrees /s. We calculated
      intraclass correlation coefficients (ICCs), standard error of measurement,
      standard error of measurement expressed as a %, and the smallest detectable
      change to determine reliability and measurement error. ICCs for the knee tests
      ranged from 0.74 to 0.89, whereas ICC values for the shoulder tests ranged from
      0.72 to 0.94. Measurement error was highest for the concentric test of the knee
      extensors and lowest for the concentric test of shoulder external rotators.

PMID- 29321060
TI  - "Available upon request": not good enough for microbiome data!

PMID- 29321058
TI  - Graphene oxide conjugated with polymers: a study of culture condition to
      determine whether a bacterial growth stimulant or an antimicrobial agent?
AB  - BACKGROUND: The results showed that the deciding factor is the culture medium in
      which the bacteria and the graphene oxide (GO) are incubated at the initial
      manipulation step. These findings allow better use of GO and GO-based materials
      more and be able to clearly apply them in the field of biomedical nanotechnology.
      RESULTS: To study the use of GO sheets applied in the field of biomedical
      nanotechnology, this study determines whether GO-based materials [GO, GO
      polyoxyalkyleneamine (POAA), and GO-chitosan] stimulate or inhibit bacterial
      growth in detail. It is found that it depends on whether the bacteria and GO
      based materials are incubated with a nutrient at the initial step. This is a
      critical factor for the fortune of bacteria. GO stimulates bacterial growth and
      microbial proliferation for Gram-negative and Gram-positive bacteria and might
      also provide augmented surface attachment for both types of bacteria. When an
      external barrier that is composed of GO-based materials forms around the surface
      of the bacteria, it suppresses nutrients that are essential to microbial growth
      and simultaneously produces oxidative stress, which causes bacteria to die,
      regardless of whether they have an outer-membrane-Gram-negative-bacteria or lack
      an outer-membrane-Gram-positive-bacteria, even for high concentrations of
      biocompatible GO-POAA. The results also show that these GO-based materials are
      capable of inducing reactive oxygen species (ROS)-dependent oxidative stress on
      bacteria. Besides, GO-based materials may act as a biofilm, so it is hypothesized
      that they suppress the toxicity of low-dose chitosan. CONCLUSION: Graphene oxide
      is not an antimicrobial material but it is a general growth enhancer that can act
      as a biofilm to enhance bacterial attachment and proliferation. However, GO-based
      materials are capable of inducing ROS-dependent oxidative stress on bacteria. The
      applications of GO-based materials can clearly be used in antimicrobial surface
      coatings, surface-attached stem cells for orthopedics, antifouling for biocides
      and microbial fuel cells and microbial electro-synthesis.

PMID- 29321061
TI  - Enoxaparin attenuates doxorubicin induced cardiotoxicity in rats via interfering
      with oxidative stress, inflammation and apoptosis.
AB  - BACKGROUND: Doxorubicin (DOX) is commonly used in the treatment of many types of
      cancers but its cardiotoxicity is limiting its clinical use. Beyond its
      anticoagulant action, enoxaparin (ENX), a low molecular weight heparin, has been
      shown to exert multiple pharmacological actions including antioxidant, anti
      inflammatory and antiapoptotic effects. Therefore, the current study aimed to
      assess if ENX could ameliorate cardiotoxicity induced by DOX. METHODS: Twenty-one
      adult male Wistar albino rats were randomly allocated into three groups (n = 7
      each) of control, receiving 0.9% saline (i.p.), DOX, receiving 2.5 mg/kg of DOX
      (i.p.) thrice weekly; and DOX + ENX, receiving ENX (250 IU/kg/day i.p.) and a DOX
      dose equivalent to that of the DOX only group. RESULTS: DOX-induced
      cardiotoxicity was indicated by marked increases in cardiac troponin I (cTnI) and
      severe histological lesions, which significantly correlated with cardiotoxicity,
      oxidative stress, inflammation and apoptosis markers, compared to controls. DOX
      group also showed elevations in malondialdehyde (MDA), a marker of oxidative
      stress, and reductions in total antioxidant capacity (TAC). Cardiac inflammatory
      markers including tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta
      (IL-1beta) and caspase-3, an apoptotic marker, were also elevated in the DOX
      group. DOX, however, did not significantly alter brain natriuretic peptide (BNP)
      levels. ENX significantly attenuated, but not completely reversed, DOX-induced
      cardiotoxicity through lowering cTnI and improving cardiomyopathy
      histopathological scores as compared to the DOX group. ENX also decreased MDA,
      increased TAC of rats' heart to levels relatively comparable to control.
      Significant reductions in TNF-alpha, IL-1beta and caspase-3 were also observed
      following ENX treatment relative to the DOX only group. CONCLUSIONS:
      Collectively, these results describe a cardioprotective effect for ENX against
      DOX-induced cardiotoxicity which is likely facilitated via suppression of
      oxidative stress, inflammation and apoptosis.

PMID- 29321062
TI  - Notch signaling triggered via the ligand DLL4 impedes M2 macrophage
      differentiation and promotes their apoptosis.
AB  - BACKGROUND: Notch signaling controls many cellular processes, including cell fate
      determination, cell differentiation, proliferation and apoptosis. In mammals,
      four Notch receptors (Notch 1-4) can interact with five distinct ligands
      [Jagged1, Jagged2, Delta-like 1 (DLL1), DLL3, and DLL4]. We previously reported
      that Notch activation is modulated in endothelial cells and monocytes during
      inflammation and showed that inflammation upregulates DLL4 on endothelial cells.
      DLL4 promotes differentiation of blood monocytes into proinflammatory M1
      macrophages. Here, we further investigated the ability of DLL4 to interfere with
      the polarization of blood monocytes into immunosuppressive M2 macrophages.
      METHODS: Human blood monocytes were differentiated in vitro into M0 macrophages
      and then polarized into M1 or M2 macrophages with LPS/IFNgamma and IL-4,
      respectively. Polarization steps were performed in the presence of immobilized
      recombinant DLL4. Immune phenotype and apoptosis of macrophage subsets were
      analyzed and quantified by flow cytometry. Regulatory effects of DLL4 on gene
      expression, cell signaling and apoptotic pathways were investigated by QPCR and
      western blots. RESULTS: The phenotype of M2 macrophages was subject to specific
      alterations in the presence of recombinant DLL4. DLL4 inhibits the upregulation
      of IL-4 induced M2 markers such as CD11b, CD206, and CD200R. Survival of
      macrophages upon M2 polarization was also strongly reduced in the presence of
      DLL4. DLL4 induces a caspase3/7-dependent apoptosis during M2 but not M1
      macrophage polarization. The Notch ligand DLL1 has no apoptotic effect. Both DLL4
      signaling via Notch1 as well as DLL4-mediated apoptosis are Notch-dependent.
      Fully differentiated M2 macrophages became resistant to DLL4 action.
      Mechanistically, DLL4 selectively upregulates gene expression in macrophages upon
      M2 polarization, thereby affecting the Notch pattern (Notch1, 3, Jag1), activity
      (HES1), and transcription (IRF5, STAT1). The pro-apoptotic effectors Bax and Bak
      and the BH3-only proteins Bid and Bim seem to convey DLL4 apoptotic signal.
      CONCLUSION: Interplay between the DLL4/Notch and IL-4/IL-4R signaling pathways
      impairs M2 differentiation. Thus, DLL4 may drive a Notch-dependent selection
      process not only by promoting M1 macrophage differentiation but also by
      preventing M2 macrophage differentiation through inhibition of M2-specific gene
      expression and apoptotic cell death.

PMID- 29321063
TI  - First clinical case report of local microinjection of autologous fat and adipose
      derived stromal vascular fraction for perianal fistula in Crohn's disease.
AB  - : Mesenchymal stem cell therapy is a promising treatment for perianal Crohn's
      fistulas refractory to conventional therapy, which are an extremely morbid
      complication and a true therapeutic challenge. Autologous adipose-derived stromal
      vascular fraction (ADSVF) is an easily accessible source of cells with
      angiogenic, anti-inflammatory, immunomodulatory, and regenerative properties.
      Here, we describe a case involving a patient with severe perianal Crohn's
      fistulas refractory to the best medical and surgical practices who received local
      treatment with ADSVF and microfat. This patient was first examined under
      anesthesia with drainage via seton placement; 1 week later, on a single day, he
      underwent adipose tissue extraction, ADSVF and microfat preparation, and the
      local injection of 14 ml of microfat and approximately 20 million viable ADSVF
      cells into the soft tissue around the fistulas. No serious adverse events were
      observed. At the first endpoint at 12 weeks, the fistula had clinically healed
      with complete re-epithelialization of all external openings; no fistula tract was
      detected on magnetic resonance imaging, confirming this finding. This good
      clinical outcome was sustained at 48 weeks and was associated with a reduction in
      the severity of perianal disease and an improvement in quality of life. The
      current case highlights the therapeutic potential of a new cellular treatment for
      Crohn's patients with refractory perianal fistulas based on the innovative
      hypothesis that the combined action of ADSVF in association with the trophic
      characteristics of a microfat graft could be beneficial for this condition. TRIAL
      REGISTRATION: EudraCT number 201325, NCT02520843 . Registered on 5 August 2015.

PMID- 29321064
TI  - The role of ACE2, angiotensin-(1-7) and Mas1 receptor axis in glucocorticoid
      induced intrauterine growth restriction.
AB  - BACKGROUND: Plasma and urine levels of the potent vasodilator Ang-(1-7) are
      elevated in mid and late pregnancy and are correlated with elevated placental
      angiogenesis, fetal blood flow, and rapid fetal growth. We hypothesized that Ang
      (1-7), its receptor (Mas1) and the enzymes involved in Ang-(1-7) production (ACE2
      and Membrane metallo-endopeptidase; MME) are down regulated in response to
      glucocorticoid administration contributing to IUGR. METHODS: Pregnant female
      Sprague-Dawley rats were injected with dexamethasone (DEX; 0.4 mg/kg/day)
      starting from 14 day gestation (dg) till sacrifice at 19 or 21 dg while control
      groups were injected with saline (n = 6/group). The gene and protein expression
      of ACE2, MME, Ang-(1-7) and Mas1 receptor in the placental labyrinth (LZ) and
      basal zones (BZ) were studied. RESULTS: DEX administration caused a reduction in
      LZ weight at 19 and 21 dg (p < 0.001). IUGR, as shown by decreased fetal weights,
      was evident in DEX treated rats at 21 dg (p < 0.01). ACE2 gene expression was
      elevated in the LZ of control placentas at 21 dg (p < 0.01) compared to 19 dg and
      DEX prevented this rise at both gene (p < 0.01) and protein levels (p < 0.05). In
      addition, Ang-(1-7) protein expression in LZ was significantly reduced in DEX
      treated rats at 21 dg (p < 0.05). On the other hand, Mas1 and MME were
      upregulated in LZ at 21 dg in both groups (p < 0.05 and p < 0.001, respectively).
      CONCLUSION: The results of this study indicate that a reduced expression of ACE2
      and Ang-(1-7) in the placenta by DEX treatment may be responsible for IUGR and
      consequent disease programming later in life.

PMID- 29321065
TI  - Developmental changes in shortening of pro-saccade reaction time while
      maintaining neck flexion position.
AB  - BACKGROUND: We investigated developmental changes in shortening of pro-saccade
      reaction time while maintaining neck flexion. METHODS: Subjects comprised 135
      children (3-14 years) and 29 young adults (19-23 years). Children were divided
      into six groups in 2-year age strata. Pro-saccade reaction tasks for 30 s were
      performed in neck rest and flexion positions. Reaction times under each position
      were averaged in every 10-s period. RESULTS: Under neck rest position, reaction
      time in the 0-10 s period was significantly longer in the 3- to 4-year-old group
      than in the 5- to 6-year-old group and above. No significant age effect was found
      for reaction time in the 0-10 s period in the 5- to 6-year-old group and above.
      Although a significant effect of neck flexion was not observed until the 9- to 10
      year-old group, significant shortening of reaction time with neck flexion was
      found in the 11- to 12-year-old group and above. Furthermore, this shortening was
      maintained until the first 20-s period in the 11- to 12-year-old group and during
      the entire 30 s in the 13- to 14-year-old and above. CONCLUSIONS: These results
      suggest that brain activation with the maintenance of neck flexion, related to
      shortening of the pro-saccade reaction time, was found from a later age of
      approximately 11 years and above, compared with the age at which information
      processing function in the pro-saccade was enhanced. In addition, brain
      activation with the maintenance of neck flexion was sustained longer with age.

PMID- 29321066
TI  - Perioperative management of antiplatelet therapy in patients undergoing non
      cardiac surgery following coronary stent placement: a systematic review.
AB  - BACKGROUND: The correct perioperative management of antiplatelet therapy (APT) in
      patients undergoing non-cardiac surgery (NCS) is often debated by clinicians.
      American College of Cardiology (ACC) and American Heart Association (AHA)
      guidelines recommend postponing elective NCS at least 3 months after stent
      implantation. Regardless of the timing of surgery, ACC/AHA guidelines recommend
      continuing at least ASA throughout the perioperative period and ideally
      continuing dual APT (DAPT) therapy "unless surgery demands discontinuation." The
      objective of this review was to ascertain the risks and benefits of APT in the
      perioperative period, to assess how these risks and benefits vary by APT
      management, and the significance of length of time since stent implantation
      before operative intervention. METHODS: PubMed, Web of Science, and Scopus were
      searched from inception through October 2017. Articles were included if patients
      were post PCI with stent placement (bare metal [BMS] or drug eluting [DES]),
      underwent elective NCS, and had rates of major adverse cardiac events (MACE) or
      bleeding events associated with pre and perioperative APT therapy. RESULTS: Of
      4882 screened articles, we included 16 studies in the review (1 randomized
      controlled trial and 15 observational studies). Studies were small (< 50: n = 5,
      51-150: n = 5, >150: n = 6). All studies included DES with 7 of 16 also including
      BMS. Average time from stent to NCS was variable (< 6 months: n = 3, 6-12 months:
      n = 1, > 12 months: n = 6). At least six different APT strategies were described.
      Six studies further utilized bridging protocols using three different
      pharmacologic agents. Studies typically included multiple surgical fields with
      varying degrees of invasiveness. Across all APT strategies, rates of
      MACE/bleeding ranged from 0 to 21% and 0 to 22%. There was no visible trend in
      MACE/bleeding rates within a given APT strategy. Stratifying the articles by type
      of surgery, timing of discontinuation of APT therapy, bridging vs. no bridging,
      and time since stent placement did not help explain the heterogeneity.
      CONCLUSIONS: Evidence regarding perioperative APT management in patients with
      cardiac stents undergoing NCS is insufficient to guide practice. Other clinical
      factors may have a greater impact than perioperative APT management on MACE and
      bleeding events. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016036607.

PMID- 29321067
TI  - The effects of essential oil mouthrinses with or without alcohol on plaque and
      gingivitis: a randomized controlled clinical study.
AB  - BACKGROUND: The efficacy of several variants of essential oil mouthrinses has
      been studied extensively. This is the first study to compare the anti-plaque and
      anti-gingivitis efficacy of two marketed essential oil mouthrinses: one is an
      alcohol containing mouthrinse and the other one is an alcohol-free mouthrinse.
      METHODS: This examiner-blind, parallel-group study randomized subjects to three
      groups: 1) Mechanical Oral Hygiene (MOH) only; 2) MOH plus Alcohol-Containing
      essential oil Mouthrinse (ACM); 3) MOH plus Alcohol-Free essential oil Mouthrinse
      (AFM). Primary endpoint was whole-mouth mean Modified Gingival Index (MGI) at six
      months. Secondary endpoints included whole-mouth mean MGI at one and three
      months, and whole-mouth mean Plaque Index (PI) and whole-mouth mean Bleeding
      Index (BI) at one, three and six months. Safety assessments were conducted at all
      time points. RESULTS: A total of 370 subjects were enrolled; 348 subjects
      completed the study. After six months, subjects using essential oil mouthrinses
      with or without alcohol showed significant reduction (p < 0.001) in gingivitis
      (28.2% and 26.7%, respectively) and significant reduction (p < 0.001) in plaque
      (37.8% and 37.0%, respectively), compared to those performing MOH only.
      Significant reductions in MGI, PI, and BI (p < 0.001) were observed at one and
      three months and also at six months for mean BI. No statistically significant
      differences were observed for all measured indices between ACM and AFM groups at
      any time point. Both mouthrinses were well tolerated. CONCLUSIONS: No significant
      differences were observed in the efficacy of ACM and AFM to reduce plaque and
      gingivitis, when used in addition to MOH, over six months. TRIAL REGISTRATION:
      The trial was registered on clinicaltrials.gov on November 30, 2016. The
      registration number is NCT02980497 .

PMID- 29321068
TI  - Psychosocial issues discovered through reflective group dialogue between medical
      students.
AB  - BACKGROUND: The biopsychosocial model is a comprehensive approach emphasizing
      holistic medical care. However, medical curricula that incorporate narrative
      reflective writing and group dynamic discussion of psychosocial issues among
      patients and their family members in reflective dialogue groups are currently
      underutilized. The aim of this study was to determine psychosocial issues among
      patients and their family members through medical students' reflective dialogue
      groups. METHODS: This study was completed as part of a pediatric clerkship. Fifty
      medical students were rotated to the department of Pediatrics. They completed a
      narrative writing assignment concerning patients' psychosocial issues and
      participated in a reflective group discussion during the rotation. The recordings
      of the six reflective group sessions were transcribed for thematic analysis. A
      six-step theme generation process was conducted in the first reading stage of all
      transcripts by four researchers. Subsequently, initial codes were generated and
      potential themes sought before possible themes were reviewed and thematic maps
      generated. Names for each theme were defined and a scholarly report of the
      analysis was presented through a consensus-based approach. RESULTS: A total of
      108 psychosocial issues were coded and categorized as the following six main
      themes: medical communication, the intricate medical ecological system, role and
      function of a family, development of medical professionalism, ethical dilemmas,
      and various patient perspectives from diverse cultural backgrounds. All these
      themes underlie the complexity of clinical encounters. CONCLUSIONS: Clinical care
      is an extremely complex interactive ecological network involving human behavior,
      family, and public health care systems. The discovery of psychosocial problems by
      medical students as narrators in this study illustrates that medical care should
      focus not only on illnesses but also patients' psychosocial narratives.

PMID- 29321069
TI  - Gastroenterologist and primary care perspectives on a post-endoscopy discharge
      policy: impact on clinic wait times, provider satisfaction and provider workload.
AB  - BACKGROUND: To reduce unnecessary ambulatory gastroenterology (GI) visits and
      increase access to GI care, San Francisco Health Network gastroenterologists and
      primary care providers implemented guidelines in 2013 that discharged certain
      patients back to primary care after endoscopy with formal written
      recommendations. This study assesses the longer-term impact of this policy on GI
      clinic access, workflow, and provider satisfaction. METHODS: An email-based
      survey assessed gastroenterologist and primary care provider (PCP) opinions about
      the discharge process. Administrative data and chart review were used to assess
      clinic access, intervention fidelity, and re-referral rates. RESULTS: 102/299
      (34%) of PCPs and 5/7 (71%) of gastroenterologists responded to the survey. 74%
      of PCPs and 100% of gastroenterologists were satisfied or very satisfied with the
      discharge process. 80% of gastroenterologists believed the discharge process
      decreased their workload, while 53.5% of primary care providers believed it
      increased their workload. 6.7% of patients discharged to primary care in 2013 had
      re-referrals to GI. Wait time for the third-next-available new outpatient GI
      clinic appointment had previously decreased from 158 days (2012, pre
      intervention) to 74 days (2013, post-intervention). In 2015, wait time was 19
      days (p < 0.001 for 2012 vs. 2015). CONCLUSIONS: Primary care providers and
      gastroenterologists are satisfied with an intervention to discharge patients from
      gastroenterology to primary care after certain endoscopic procedures, although
      this conclusion is limited by a relatively low PCP survey response rate.
      Discharging appropriate patients using consensus criteria from the
      gastroenterology clinic was instrumental in sustainably reducing clinic wait
      times with low re-referral rates.

PMID- 29321070
TI  - The effect of methamphetamine abuse on dental caries and periodontal diseases in
      an Eastern China city.
AB  - BACKGROUND: Dental diseases are among the most frequently reported health
      problems in drug abusers. However, few studies have been conducted on oral health
      of methamphetamine (meth) abusers in China. The aim of the present study was to
      investigate the caries and periodontal health profile of former meth abusers in
      Eastern China. METHODS: A cross-sectional study was conducted on 162 former meth
      abusers in the male Zhoushan Compulsory Detoxification Center. A standardized
      questionnaire, which collected information about age, drug-use duration /
      pattern, oral hygiene habit and systemic diseases, was administered. Then, a
      dental examination was performed to investigate the severity of dental caries and
      periodontal diseases. In evaluating dental caries, the prevalence of dental
      caries, the scores of decayed teeth (DT), missing teeth (MT), filled teeth (FT),
      and decayed, missing, filled teeth (DMFT) were recorded. In evaluating
      periodontal diseases, community periodontal index (CPI), and the prevalence of
      gingival bleeding, dental calculus, periodontal pocket and loose teeth, were
      recorded. Additionally, the non-parametric test was adopted to analyze the
      potential risk factors via SPSS. RESULTS: All the participants abused meth by
      inhalation. The mean scores of DT, MT, FT and DMFT in the former meth users were
      2.72 +/- 2.78, 3.07 +/- 3.94, 0.33 +/- 1.03 and 6.13 +/- 5.20 respectively. The
      prevalence of gingival bleeding, dental calculus, periodontal pocket and loose
      teeth was 97.53%, 95.68%, 51.23% and 9.26% respectively. The DT, DMFT and CPI
      scores in those who had abused meth for longer than 4 years were significantly
      higher than those who abused for less than 4 years (P = 0.039, 0.045, P < 0.001,
      respectively). The DT score in those who brushed their teeth more than twice a
      day were significantly lower than those who brushed less (P = 0.018).
      CONCLUSIONS: The status of caries and periodontal diseases among former male meth
      users in Eastern China was poor. Prolonged drug abuse and lower frequency of
      tooth brushing may be the risk factors of their poor status of caries and
      periodontal diseases.

PMID- 29321071
TI  - Head circumference - a useful single parameter for skull volume development in
      cranial growth analysis?
AB  - BACKGROUND: The measurement of maximal head circumference is a standard procedure
      in the examination of childrens' cranial growth and brain development. The
      objective of the study was to evaluate the validity of maximal head circumference
      to cranial volume in the first year of life using a new method which includes ear
      to-ear over the head distance and maximal cranial length measurement. METHODS: 3D
      surface scans for cranial volume assessment were conducted in this method
      comparison study of 44 healthy Caucasian children (29 male, 15 female) at the
      ages of 4 and 12 months. RESULTS: Cranial volume increased from measurements made
      at 4 months to 12 months of age by an average of 1174 +/- 106 to 1579 +/- 79 ml.
      Maximal cranial circumference increased from 43.4 +/- 9 cm to 46.9 +/- 7 cm and
      the ear-to ear measurement increased from 26.3 +/- 21 cm to 31.6 +/- 18 cm at the
      same time points. There was a monotone association between maximal head
      circumference (HC) and increase in volume, yet a backwards inference from maximal
      circumference to the volume had a predictive value of only 78% (adjusted R2).
      Including the additional measurement of distance from ear to ear strengthened the
      ability of the model to predict the true value attained to 90%. The addition of
      the parameter skull length appeared to be negligible. CONCLUSION: The results
      demonstrate that for a distinct improvement in the evaluation of a physiological
      cranial volume development, the additional measurement of the ear-to ear distance
      using a measuring tape is expedient, and, especially for cases with pathological
      skull changes, such as craniosynostosis, ought to be conducted.

PMID- 29321072
TI  - Tissue-specific transcriptomes of Anisakis simplex (sensu stricto) and Anisakis
      pegreffii reveal potential molecular mechanisms involved in pathogenicity.
AB  - BACKGROUND: Larval stages of the sibling species of parasitic nematodes Anisakis
      simplex (sensu stricto) (s.s.) (AS) and Anisakis pegreffii (AP) are responsible
      for a fish-borne zoonosis, known as anisakiasis, that humans aquire via the
      ingestion of raw or undercooked infected fish or fish-based products. These two
      species differ in geographical distribution, genetic background and peculiar
      traits involved in pathogenicity. However, thus far little is known of key
      molecules potentially involved in host-parasite interactions. Here, high
      throughput RNA-Seq and bioinformatics analyses of sequence data were applied to
      the characterization of the whole sets of transcripts expressed by infective
      larvae of AS and AP, as well as of their pharyngeal tissues, in a bid to identify
      transcripts potentially involved in tissue invasion and host-pathogen interplay.
      RESULTS: Approximately 34,000,000 single-end reads were generated from cDNA
      libraries for each species. Transcripts identified in AS and AP encoded 19,403
      and 10,424 putative peptides, respectively, and were classified based on homology
      searches, protein motifs, gene ontology and biological pathway mapping.
      Differential gene expression analysis yielded 226 and 339 transcripts upregulated
      in the pharyngeal regions of AS and AP, respectively, compared with their
      corresponding whole-larvae datasets. These included proteolytic enzymes,
      molecules encoding anesthetics, inhibitors of primary hemostasis and virulence
      factors, anticoagulants and immunomodulatory peptides. CONCLUSIONS: This work
      provides the scientific community with a list of key transcripts expressed by AS
      and AP pharyngeal tissues and corresponding annotation information which
      represents a ready-to-use resource for future functional studies of biological
      pathways specifically involved in host-parasite interplay.

PMID- 29321073
TI  - Insufficient sensitivity of joint aspiration during the two-stage exchange of the
      hip with spacers.
AB  - BACKGROUND: Evaluation of infection persistence during the two-stage exchange of
      the hip is challenging. Joint aspiration before reconstruction is supposed to
      rule out infection persistence. Sensitivity and specificity of synovial fluid
      culture and synovial leucocyte count for detecting infection persistence during
      the two-stage exchange of the hip were evaluated. METHODS: Ninety-two aspirations
      before planned joint reconstruction during the two-stage exchange with spacers of
      the hip were retrospectively analyzed. RESULTS: The sensitivity and specificity
      of synovial fluid culture was 4.6 and 94.3%. The sensitivity and specificity of
      synovial leucocyte count at a cut-off value of 2000 cells/MUl was 25.0 and 96.9%.
      C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) values were
      significantly higher before prosthesis removal and reconstruction or spacer
      exchange (p = 0.00; p = 0.013 and p = 0.039; p = 0.002) in the infection
      persistence group. Receiver operating characteristic area under the curve values
      before prosthesis removal and reconstruction or spacer exchange for ESR were
      lower (0.516 and 0.635) than for CRP (0.720 and 0.671). CONCLUSIONS: Synovial
      fluid culture and leucocyte count cannot rule out infection persistence during
      the two-stage exchange of the hip.

PMID- 29321076
TI  - Being influential or being misleading? Citation bias in psychiatric research and
      practice.

PMID- 29321074
TI  - Patient and case characteristics associated with 'no paramedic treatment' for low
      acuity cases referred for emergency ambulance dispatch following a secondary
      telephone triage: a retrospective cohort study.
AB  - BACKGROUND: Predicting case types that are unlikely to be treated by paramedics
      can aid in managing demand for emergency ambulances by identifying cases suitable
      for alternative management pathways. The aim of this study was to identify the
      patient characteristics and triage outcomes associated with 'no paramedic
      treatment' for cases referred for emergency ambulance dispatch following
      secondary telephone triage. METHODS: A retrospective cohort analysis was
      conducted of cases referred for emergency ambulance dispatch following secondary
      telephone triage between September 2009 and June 2012. Multivariable logistic
      regression modelling was used to identify explanatory variables associated with
      'no paramedic treatment'. RESULTS: There were 19,041 cases eligible for inclusion
      in this study over almost three years, of which 8510 (44.7%) were not treated
      after being sent an emergency ambulance following secondary triage. Age, time of
      day, pain, triage guideline group, and comorbidities were associated with 'no
      paramedic treatment'. In particular, cases 0-4 years of age or those with
      psychiatric conditions were significantly less likely to be treated by
      paramedics, and increasing pain resulted in higher rates of paramedic treatment.
      CONCLUSIONS: This study highlights that case characteristics can be used to
      identify particular case types that may benefit from care pathways other than
      emergency ambulance dispatch. This process is also useful to identify gaps in the
      alternative care pathways currently available. These findings offer the
      opportunity to optimise secondary telephone triage services to support their
      strategic purpose of minimising unnecessary emergency ambulance demand and to
      match the right case with the right care pathway.

PMID- 29321077
TI  - Social anxiety disorder: looking back and moving forward.
AB  - Fifty years have passed since social anxiety disorder (SAD) was first
      differentiated from other phobias. In the years since research has largely
      aligned with the zeitgeist of categorical classificatory frameworks, and has
      spanned identifying causes, maintenance factors and innovative interventions.
      Despite significant advances in the field, the capacity to conceptualise SAD as
      an independent entity is limited given the heterogeneity and dimensionality of
      diagnostic criteria, high rates of comorbidity, and non-specificity of
      aetiological mechanisms, maintaining factors and approaches to treatment. The
      Research Domain Criteria (RDoC) initiative was developed in an effort to overcome
      the inherent limitations posed by descriptive diagnostic systems - particularly
      in terms of reliability and validity - and in doing so seeks to facilitate
      research into underlying pathophysiological and behavioural mechanisms that cut
      across traditional diagnostic boundaries. The RDoC framework is furnished with a
      'matrix', which in essence corresponds to a set of research principles that
      attempt to reconcile neuroscience and psychopathology. This review outlines a
      rationale for integrating SAD research with the RDoC approach, and offers
      examples of how future studies may wish to frame hypotheses and design
      experiments as the field moves towards classifying dimensions of psychopathology
      through a mechanistic understanding of underlying neurobiological and behavioural
      processes.

PMID- 29321075
TI  - A phase I, open-label trial on the safety and immunogenicity of the adjuvanted
      tuberculosis subunit vaccine H1/IC31(r) in people living in a TB-endemic area.
AB  - BACKGROUND: H1/IC31(r) is a tuberculosis (TB) subunit vaccine candidate
      consisting of the fusion protein of Ag85B and ESAT-6 (H1) formulated with the
      IC31(r) adjuvant. Previous trials have reported on the H1/IC31(r) vaccine in M.
      tuberculosis (Mtb)-naive, BCG-vaccinated and previously Mtb-infected individuals.
      In this trial, conducted between December 2008 and April 2010, the safety and
      immunogenicity of H1/IC31(r) was assessed in participants living in Ethiopia - a
      highly TB-endemic area. METHODS: Healthy male participants aged 18-25 years were
      recruited into four groups. Participants in group 1 (N = 12) and group 2 (N = 12)
      were Tuberculin Skin Test (TST) negative and QuantiFERON-TB Gold in-tube test
      (QFT) negative (Mtb-naive groups), participants in group 3 (N = 3) were TST
      positive and QFT negative (BCG group), and participants in group 4 (N = 12) were
      both TST and QFT positive (Mtb-infected group). H1 vaccine alone (group 1) or H1
      formulated with the adjuvant IC31(r) (groups 2, 3 and 4) was administered
      intramuscularly on day 0 and day 56. Safety and immunogenicity parameters were
      evaluated for up to 32 weeks after day 0. RESULTS: The H1/IC31(r)vaccine was safe
      and generally well tolerated. There was little difference among the four groups,
      with a tendency towards a higher incidence of adverse events in Mtb-infected
      compared to Mtb-naive participants. Two serious adverse events were reported in
      the Mtb-infected group where a relationship to the vaccine could not be excluded.
      In both cases the participants recovered without sequelae within 72 h.
      Immunogenicity assays, evaluated in the 29 participants who received both
      vaccinations, showed a stronger response to TB antigens in the Mtb-naive group
      vaccinated with the adjuvant. CONCLUSION: The trial confirmed the need for an
      adjuvant for the vaccine to be immunogenic and highlighted the importance of
      early phase testing of a novel TB vaccine candidate in TB-endemic areas. TRIAL
      REGISTRATION: ClinicalTrials.gov, ID: NCT01049282. Retrospectively registered on
      14 January 2010.

PMID- 29321078
TI  - Duration of Contact Precautions for Acute-Care Settings.

PMID- 29321079
TI  - The enactment stage of end-of-life decision-making for children.
AB  - OBJECTIVES: Typically pediatric end-of-life decision-making studies have examined
      the decision-making process, factors, and doctors' and parents' roles. Less
      attention has focussed on what happens after an end-of-life decision is made;
      that is, decision enactment and its outcome. This study explored the views and
      experiences of bereaved parents in end-of-life decision-making for their child.
      Findings reported relate to parents' experiences of acting on their decision. It
      is argued that this is one significant stage of the decision-making process.
      METHODS: A qualitative methodology was used. Semi-structured interviews were
      conducted with bereaved parents, who had discussed end-of-life decisions for
      their child who had a life-limiting condition and who had died. Data were
      thematically analysed. RESULTS: Twenty-five bereaved parents participated.
      Findings indicate that, despite differences in context, including the child's
      condition and age, end-of-life decision-making did not end when an end-of-life
      decision was made. Enacting the decision was the next stage in a process. Time
      intervals between stages and enactment pathways varied, but the enactment was
      always distinguishable as a separate stage. Decision enactment involved making
      further decisions - parents needed to discern the appropriate time to implement
      their decision to withdraw or withhold life-sustaining medical treatment.
      Unexpected events, including other people's actions, impacted on parents enacting
      their decision in the way they had planned. Several parents had to re-implement
      decisions when their child recovered from serious health issues without medical
      intervention. Significance of results A novel, critical finding was that parents
      experienced end-of-life decision-making as a sequence of interconnected stages,
      the final stage being enactment. The enactment stage involved further decision
      making. End-of-life decision-making is better understood as a process rather than
      a discrete once-off event. The enactment stage has particular emotional and
      practical implications for parents. Greater understanding of this stage can
      improve clinician's support for parents as they care for their child.

PMID- 29321080
TI  - Prenatal vitamin D status and offspring's growth, adiposity and metabolic health:
      a systematic review and meta-analysis.
AB  - In this systematic review and meta-analysis of observational studies, we aimed to
      estimate the associations between prenatal vitamin D status and offspring growth,
      adiposity and metabolic health. We searched the literature in human studies on
      prenatal vitamin D status and offspring growth in PubMed, up to July 2017.
      Studies were selected according to their methodological quality and outcomes of
      interest (anthropometry, fat mass and diabetes in offspring). The inverse
      variance method was used to calculate the pooled mean difference (MD) with 95 %
      CI for continuous outcomes, and the Mantel-Haenszel method was used to calculate
      the pooled OR with 95 % CI for dichotomous outcomes. In all, thirty observational
      studies involving 35 032 mother-offspring pairs were included. Vitamin D status
      was evaluated by circulating 25-hydroxyvitamin D (25(OH)D) level. Low vitamin D
      status was based on each study's cut-off for low 25(OH)D levels. Low prenatal
      vitamin D levels were associated with lower birth weight (g) (MD -100.69; 95 % CI
      -162.25, -39.13), increased risk of small-for-gestational-age (OR 1.55; 95 % CI
      1.16, 2.07) and an elevated weight (g) in infant at the age of 9 months (g) (MD
      119.75; 95 % CI 32.97, 206.52). No associations were observed between prenatal
      vitamin D status and other growth parameters at birth, age 1 year, 4-6 years or 9
      years, nor with diabetes type 1. Prenatal vitamin D may play a role in infant
      adiposity and accelerated postnatal growth. The effects of prenatal vitamin D on
      long-term metabolic health outcomes in children warrant future studies.

PMID- 29321081
TI  - The clock: Not a question of time.

PMID- 29321082
TI  - Long Noncoding RNA ATB Promotes Proliferation, Migration, and Invasion in Bladder
      Cancer by Suppressing MicroRNA-126.
AB  - This study aimed to explore the biological functions of long noncoding RNA
      activated by transforming growth factor-beta (lncRNA-ATB) in bladder cancer
      cells. For the expressions of lncRNA-ATB, miR-126, and KRAS, T24 cells were
      transfected with their specific vectors/shRNA or mimic/inhibitor. Then cell
      viability, migration, invasion, and apoptosis as well as the protein levels of
      apoptosis-related factors and PI3K/AKT and mTOR signal pathways were measured.
      The relationships of lncRNA-ATB and miR-126 or miR-126 and KRAS were analyzed by
      Dual-Luciferase Reporter assay. Functional experiments showed that lncRNA-ATB
      overexpression significantly promoted cell viability, migration, and invasion in
      T24 cells. lncRNA-ATB was a molecular sponge of miR-126 and exerted tumor
      promoting effects by downregulation of miR-126. Moreover, KRAS was a direct
      target of miR-126 and was negatively regulated by miR-126. Finally,
      overexpression of KRAS increased cell viability, migration, and invasion, as well
      as activated PI3K/AKT and mTOR signaling pathways in T24 cells. The results
      revealed that lncRNA-ATB was an oncogene, which promoted cell proliferation,
      migration, and invasion by regulating miR-126 in bladder cancer. These findings
      may provide a potential prognostic biomarker and a therapeutic target for bladder
      cancer.

PMID- 29321083
TI  - MicroRNA-338-3p Suppresses Proliferation of Human Liver Cancer Cells by Targeting
      SphK2.
AB  - Recent studies have revealed abnormal expression of miRNAs in various tumors.
      Although microRNA-338-3p (miR-338-3p) plays an important role in many types of
      tumors, its influence on liver cancer (LC) is unknown. In this study, we found
      that expression of miR-338-3p was decreased in LC cells and tissues. Colony
      formation and cell proliferation were suppressed by enhanced expression of miR
      338-3p in LC cells. Moreover, miR-338-3p targeted sphingosine kinase 2 (SphK2).
      Silencing of SphK2 had an identical influence as overexpression of miR-338-3p in
      LC cells. Overexpression of SphK2 without the 3'-untranslated region remarkably
      enhanced the growth suppression triggered by miR-338-3p in LC cells. These
      findings indicate that miR-338-3p influences the development of LC by targeting
      SphK2, suggesting that miR-338-3p can be targeted as an innovative therapeutic
      strategy for LC.

PMID- 29321084
TI  - miR-143 Inhibits Cell Proliferation of Gastric Cancer Cells Through Targeting
      GATA6.
AB  - Recent studies have suggested that the dysregulation of microRNAs (miRNAs) plays
      a critical role in the progression of human cancers, including gastric cancer
      (GC). miR-143 had been reported to function as a tumor suppressor in GC. However,
      the exact molecular mechanism of how miR-143 participates in GC progression
      remains to be determined. In this present study, we revealed that the expression
      of miR-143 was significantly downregulated in human GC tissues and cell lines
      compared with normal tissues and a normal gastric epithelium cell line. In
      addition, upregulation of the expression of miR-143 in a GC cell line inhibited
      cell proliferation and induced cell cycle arrested in the G0/G1 phase.
      Furthermore, GATA6 was identified as a direct target of miR-143 in GC using the
      luciferase reporter assay. Upregulation of miR-143 inhibited the expression of
      GATA6 in GC cell lines. Moreover, the overexpression of GATA6 could attenuate the
      effect of miR-143 on cell proliferation in the GC cell lines. Collectively, these
      data indicated that miR-143 plays a tumor suppressor role partly through
      regulating the expression of GATA6 in GC. Therefore, targeting miR-143 may be a
      novel therapeutic method for GC.

PMID- 29321085
TI  - MicroRNA-519d-3p Inhibits Proliferation and Promotes Apoptosis by Targeting HIF
      2alpha in Cervical Cancer Under Hypoxic Conditions.
AB  - HIF-2alpha knockdown inhibits proliferation, arrests the cell cycle, and promotes
      apoptosis and autophagy under hypoxic conditions in cervical cancer. However, the
      upstream regulatory mechanism of HIF-2alpha expression is unclear. MicroRNAs
      (miRNAs) degrade target mRNAs by binding to the 3'-untranslated region of mRNAs.
      In this study, we investigated the role of miRNAs in the regulation of HIF-2alpha
      expression in cervical cancer under hypoxic conditions. miRNAs regulating HIF
      2alpha expression were predicted using TargetScan and miRanda and were determined
      in cervical cancer under hypoxic conditions by qRT-PCR. Additionally, the
      targeted regulation of HIF-2alpha by miR-519d-3p was evaluated by Western blot
      and luciferase reporter assays. Effects of miR-519d-3p and HIF-2alpha on cell
      proliferation, cell cycle, and apoptosis were analyzed by CCK-8 and flow
      cytometry assays, respectively. miR-106a-5p, miR-17-5p, miR-519d-3p, miR-526b-3p,
      and miR-20b-5p are potentially regulatory miRNAs that bound to the HIF-2alpha 3'
      untranslated region as per TargetScan and miRanda predictions. Expression of the
      five miRNAs was inhibited in HeLa cells under hypoxic conditions compared to
      normoxic conditions, and the expression of miR-519d-3p was lower than that of
      other miRNAs. Luciferase reporter assays showed that HIF-2alpha was a target of
      miR-519d-3p. Additionally, miR-519d-3p overexpression inhibited cell
      proliferation, arrested the cell cycle transition from the G1 stage to the S
      stage, and promoted cell apoptosis under hypoxic conditions in cervical cancer.
      HIF-2alpha overexpression partially reversed the effect of miR-519d-3p. In
      conclusion, miR-519d-3p overexpression suppressed proliferation, inhibited the
      cell cycle, and promoted apoptosis of HeLa cells by targeting HIF-2alpha under
      hypoxic conditions.

PMID- 29321086
TI  - MicroRNA-511 inhibits cellular proliferation and invasion in colorectal cancer by
      directly targeting hepatoma-derived growth factor.
AB  - Dysregulated microRNAs (miRNAs) expression is involved in the occurrence and
      development of colorectal cancer (CRC) through the regulation of various
      important physiological events. Hence, miRNAs may be used as effective targets
      for CRC treatment; however, this hypothesis warrants further investigation. MiRNA
      511 (miR511) plays vital roles in the progression of different tumour types.
      However, the expression, exact role and the mechanisms underlying the regulation
      of colorectal carcinogenesis and progression by miR-511 remain poorly understood.
      This study presents that miR-511 expression was decreased in CRC tissues and cell
      lines as compared with that in adjacent non-neoplastic tissues and normal human
      colon epithelium cell lines, respectively. The enforced expression of miR-511 in
      CRC cells significantly reduced cell proliferation and invasion. Hepatoma-derived
      growth factor (HDGF) was mechanically validated as a direct target of miR-511 in
      CRC. Furthermore, miR-511 was negatively associated with HDGF in CRC tissues. The
      restored HDGF expression can abrogate the tumour suppressive roles of miR-511 in
      CRC cells. More importantly, miR-511 overexpression suppressed the PI3K/AKT
      signalling pathway in CRC. These results suggest that miR-511 can potentially
      serve as a therapeutic target for the therapy of patients with CRC.

PMID- 29321087
TI  - CD47 promotes human glioblastoma invasion through activation of PI3K/Akt pathway.
AB  - Excessive expression of Cluster of Differentiation 47 (CD47) is common in various
      malignancies. The aim of this study was to investigate whether CD47 promotes
      human glioblastoma invasion and its underlying mechanism of CD47 in promoting
      glioblastoma invasion. In this study we found that CD47 expression was stronger
      in glioblastoma patients and cells in comparison with normal controls. CD47
      downregulation modulated by siRNA suppressed invasion in vitro. However,
      excessive CD47 expression modulated by transfection exerted opposite influence.
      In the meantime, excessive CD47 or knockdown CD47 expression had no effect on
      proliferation. Moreover, CD47 expression was related to AKT phosphorylation on
      cellular molecular level. AKT suppression with specific inhibitor impaired
      invasion of cells in which excessively expressed CD47, indicating that
      stimulation of PI3K/Akt pathway served as the downstream regulator of invasion
      triggered by CD47. These results suggest that CD47 might serve as a predictor of
      worse development as well as metastasis and brought about an innovative approach
      to treat glioblastoma.

PMID- 29321088
TI  - Upregulation of Long Noncoding RNA TUG1 Promotes Bladder Cancer Cell
      Proliferation, Migration, and Invasion by Inhibiting miR-29c.
AB  - Bladder cancer (BC) is one of the leading causes of cancer-related deaths in the
      world. Long noncoding RNA (lncRNA) taurine-upregulated gene 1 (TUG1) plays an
      important role in the development and progression of numerous cancers, including
      BC. However, the exact role of TUG1 in modulating BC progression is still poorly
      known. In this study, we found that TUG1 was upregulated and microRNA-29c (miR
      29c) was downregulated in BC tissues and cell lines. Overexpression of TUG1
      promoted the cell proliferation of T24 and EJ cells, whereas TUG1 knockdown had
      the opposite effect. Upregulation of TUG1 obviously facilitated the migration and
      invasion of T24 and EJ cells. In contrast, TUG1 silencing repressed the migration
      and invasion of T24 and EJ cells. Furthermore, TUG1 knockdown markedly increased
      the expression of miR-29c in vitro. On the contrary, overexpression of TUG1
      remarkably decreased the expression of miR-29c. Transfection with plasmids
      containing mutant TUG1 has no effect on the expression of miR-29c. There were
      direct interactions between miR-29c and the binding sites of TUG1. In addition,
      the inhibitory effects of small interfering RNA specific for TUG1 on BC cell
      proliferation, migration, and invasion were reversed by downregulation of miR
      29c. Collectively, our study strongly demonstrates that TUG1 promotes BC cell
      proliferation, migration, and invasion by inhibiting miR-29c, suggesting that
      lncRNA TUG1 may be a promising target for BC gene therapy.

PMID- 29321089
TI  - Silencing of E3 ubiquitin ligase RNF8 enhances ionizing radiation sensitivity of
      5 medulloblastoma cells by promoting the deubiquitination of PCNA.
AB  - DNA damage response induced by ionizing radiation (IR) is an important event that
      involved in the sensitivity and efficiency of radiotherapy in human
      medulloblastoma. RNF8 is a E3 ubiquitin ligase and has key roles in the process
      of DNA damage and repair. Our study aimed to evaluate the effect of RNF8 in the
      DNA damage repair induced by IR exposure in medulloblastoma cells. We found that
      the levels of RNF8 were significantly up-regulated by gamma-ray irradiation in a
      dose-dependent manner in medulloblastoma cells, and colocalized with gamma-H2AX,
      a sensitive marker of DNA double strand break induced by gamma-ray radiation.
      RNF8 knockdown was observed to enhanced the sensitivity of IR in medulloblastoma
      cells, as evaluated by reduced cell survival. And the apoptosis as well as cell
      cycle arrest of medulloblastoma cells were dramatically increased by RNF8
      suppression after IR treatment. Furthermore, RNF8 inhibition didn't affect the
      protein levels of BRCA1, a crucial protein involved in IR-induced DNA damage
      repair, but significantly decreased the recruitment of BRCA1 and increased the
      level of gamma-H2AX at DNA damage sites compared to the control. And a
      significant increase of OTM was observed in medulloblastoma cells treated by RNF8
      shRNA after exposure to IR, indicating the effect of RNF8 on DNA damage and
      repair. Additionally, PCNA, a major target for Ub modification during DNA damage
      response, was found to be mono ubiquitinated by E3 ligase RNF8 and might
      contribute to the low radiosensitivity in medulloblastoma cells. Altogether, our
      findings may provide RNF8 as a novel target for the improvement of radiotherapy
      in medulloblastoma.

PMID- 29321090
TI  - Problems and resolutions in dealing with waste disposable paper cups.
AB  - In recent years, the problem caused by waste disposable paper cups (WDPCs) has
      became a topic of great concern to scientists, and commercial companies have also
      begun to take an interest in developing processes for tackling the issue. In this
      review, the inherent problems and social barriers during the recycling of WDPCs
      are described. This review presents the major conclusions of previously published
      works focused on the utilisation of WDPCs for material and energy purposes. The
      commercial utilisation of WDPCs is also described. Some suggestions for better
      recycling of WDPCs are given in the final part of this work.

PMID- 29321091
TI  - The Downregulation of miR-200c Promotes Lactate Dehydrogenase A Expression and
      Non-Small Cell Lung Cancer Progression.
AB  - This study was aimed to investigate the function and mechanism of microRNA-200c
      (miR-200c) in the progression of non-small cell lung cancer (NSCLC). A total of
      76 patients diagnosed as having NSCLC were enrolled in this study. The expression
      level of miR-200c in NSCLC tissues and cell lines was investigated using the
      quantitative real-time polymerase chain reaction (RT-qPCR) method. We found that
      the expression of miR-200c was significantly reduced in NSCLC tissues and cell
      lines compared with normal lung tissues and the human bronchial epithelial cell
      line. Overexpression of miR-200c using the miR-200c mimic significantly
      suppressed cell proliferation and migration of NSCLC cell lines. The results of
      the luciferase reporter assay identified lactate dehydrogenase A (LDHA) as a
      direct target of miR-200c. The expression of LDHA was shown to be suppressed in
      NSCLC cell lines with miR-200c mimic transfection. Furthermore, the transfection
      of small interfering RNA (siRNA) targeting LDHA suppressed the proliferation and
      migration of NSCLC cell lines. In summary, our results presented in this study
      suggested that miR-200c was able to inhibit the proliferation and migration of
      NSCLC cells by downregulating LDHA. Therefore, miR-200c may be considered as a
      potential candidate for the treatment of NSCLC.

PMID- 29321092
TI  - MicroRNA-212 Targets Mitogen-Activated Protein Kinase 1 to Inhibit Proliferation
      and Invasion of Prostate Cancer Cells.
AB  - Prostate cancer (PCa) is the second most commonly diagnosed malignancy and the
      fifth leading cause of cancer-related deaths in males worldwide. MicroRNAs
      (miRNAs) may serve as important regulators in PCa occurrence and development.
      Therefore, understanding the expression and functions of PCa-related miRNAs may
      be beneficial for the identification of novel therapeutic methods for patients
      with PCa. In this study, miRNA-212 (miR-212) was evidently downregulated in PCa
      tissues and several PCa cell lines. Functional assays showed that the resumption
      of miR-212 expression attenuated cell proliferation and invasion and increased
      the apoptosis of PCa. In addition, mitogen-activated protein kinase 1 (MAPK1), a
      well-known oncogene, was identified as a novel target of miR-212 in PCa, as
      confirmed by bioinformatics, luciferase reporter assay, qRT-PCR, and Western blot
      analysis. Furthermore, MAPK1 expression was upregulated in PCa tissues and
      inversely correlated with miR-212 expression. Rescue experiments also
      demonstrated that restored MAPK1 expression reversed the tumor-suppressing
      effects of miR-212 on PCa cell proliferation, invasion, and apoptosis. In
      conclusion, miR-212 may exert tumor-suppressing roles in PCa by regulating MAPK1
      and could be a novel therapeutic target for treatment of patients with this
      malignancy.

PMID- 29321094
TI  - Expression and Function of Long Noncoding RNA NONHSAT129183 in Papillary Thyroid
      Cancer.
AB  - The aberrant expression of long noncoding RNAs (lncRNAs) is implicated in cancer
      development and progression. This study was aimed to investigate the expression
      and clinical significance of lncRNA NONHSAT129183 in papillary thyroid cancer
      (PTC), and to explore its roles in PTC cell proliferation, migration, and
      invasion. Our results demonstrate that lncRNA NONHSAT129183 is upregulated in
      human PTC tissues when compared with that in adjacent noncancerous thyroid
      tissue. Moreover, its expression is correlated with tumor size, lymph node
      metastasis, and TNM stage in PTC patients. lncRNA NONHSAT129183 silencing also
      significantly suppressed cell proliferation, migration, and invasion in PTC cell
      lines. In conclusion, our results suggest that lncRNA NONHSAT129183 plays a
      critical role in the regulation of PTC cell proliferation, migration, and
      invasion, providing new insights into PTC pathogenesis.

PMID- 29321096
TI  - Chemsex as edgework: towards a sociological understanding.
AB  - Sexual sessions between men, organised through mobile technologies and combined
      with stimulants intended to extend and intensify the session have been reified
      into the phenomena of 'chemsex'. Understanding chemsex requires multiple levels
      of analysis and interpretation. This paper considers chemsex through the lens of
      edgework, a sociological category for voluntary risk taking identified in 1990 by
      Stephen Lyng. Edgework activities involve a clear and present danger to the self,
      intense emotions and sensations and an opportunity to exercise specialist skills.
      Using published research and other cultural products, this paper demonstrates
      that chemsex fully exhibits all the defining features of edgework. Chemsex is
      then positioned as an activity that epitomises the (gay) citizen as consumer in a
      technocapitalist age of pharmacopornographic consumption.

PMID- 29321093
TI  - A Retrospective Comparison of the Clinical Efficacy of Gefitinib, Erlotinib, and
      Afatinib in Japanese Patients With Non-Small Cell Lung Cancer.
AB  - Tyrosine kinase inhibitors (TKIs) are very effective against non-small cell lung
      cancer (NSCLC) caused by epidermal growth factor receptor (EGFR) mutation. Before
      the approval of osimertinib in March 2016, there were only three available EGFR
      TKIs (gefitinib, erlotinib, and afatinib) for the therapy of NSCLC in Japan.
      Osimertinib can be indicated only against T790M+ lung cancer as a second-line
      therapy. However, whether gefitinib, erlotinib, or afatinib is most appropriate
      as a first-line therapy is still a controversial issue. The aim of this study was
      to compare the effectiveness of gefitinib, erlotinib, and afatinib. We
      retrospectively reviewed the records of 310 patients with the diagnosis of EGFR
      mutation-associated NSCLC including 147 patients treated with EGFR TKIs. Time to
      treatment failure and overall survival were evaluated. There were no significant
      differences in time to treatment failure (gefitinib: 9.2 months; erlotinib: 9.8
      months; afatinib: 13.1 months) and overall survival (gefitinib: 27.3 months;
      erlotinib: 29.3 months; afatinib data not available) among NSCLC patients treated
      with the three different EGFR TKIs. Subgroup analysis showed that smoking status
      has a significant influence on both time to treatment failure and overall
      survival. In conclusion, this study showed comparable clinical efficacy of
      gefitinib, erlotinib, and afatinib in Japanese patients with NSCLC.

PMID- 29321095
TI  - Sexual content in video games: an analysis of the Entertainment Software Rating
      Board classification from 1994 to 2013.
AB  - : Background Video games are widely used by children and adolescents and have
      become a significant source of exposure to sexual content. Despite evidence of
      the important role of media in the development of sexual attitudes and
      behaviours, little attention has been paid to monitor sexual content in video
      games. METHODS: Data was obtained about sexual content and rating for 23722 video
      games from 1994 to 2013 from the Entertainment Software Rating Board database;
      release dates and information on the top 100 selling video games was also
      obtained. A yearly prevalence of sexual content according to rating categories
      was calculated. Trends and comparisons were estimated using Joinpoint regression.
      RESULTS: Sexual content was present in 13% of the video games. Games rated
      'Mature' had the highest prevalence of sexual content (34.5%) followed by 'Teen'
      (30.7%) and 'E10+' (21.3%). Over time, sexual content decreased in the 'Everyone'
      category, 'E10+' maintained a low prevalence and 'Teen' and 'Mature' showed a
      marked increase. Both top and non-top video games showed constant increases, with
      top selling video games having 10.1% more sexual content across the period of
      study. CONCLUSION: Over the last 20 years, the prevalence of sexual content has
      increased in video games with a 'Teen' or 'Mature' rating. Further studies are
      needed to quantify the potential association between sexual content in video
      games and sexual behaviour in children and adolescents.

PMID- 29321097
TI  - Towards a supportive policy and commissioning environment for chemsex in England.
AB  - The use of drugs in sexual settings among gay men (colloquially referred to as
      'chemsex') was first observed in services supporting gay men in London in the
      late 2000s. A decade on and it now features as a policy issue in the UK
      Government's latest Drug Strategy, with several actions to support a health
      system response. However, reaching this point has been a slow and challenging
      process and much remains to be done to facilitate an environment in which
      evidence-based chemsex interventions can be delivered. With a view to informing
      the development of policies and services in other contexts, this case report
      examines the initiatives that have driven a response to chemsex and contributed
      to policy development in England and highlights remaining challenges to effective
      service provision.

PMID- 29321100
TI  - The changing face of critical care: Task force on tropical diseases.

PMID- 29321098
TI  - Spondylodiscitis: Diagnosis and Treatment Options.
AB  - BACKGROUND: A recent population-based study from Denmark showed that the
      incidence of spondylodiscitis rose from 2.2 to 5.8 per 100 000 persons per year
      over the period 1995-2008; the age-standardized incidence in Germany has been
      estimated at 30 per 250 000 per year on the basis of data from the Federal
      Statistical Office (2015). The early diagnosis and treatment of this condition
      are essential to give the patient the best chance of a good outcome, but these
      are often delayed because it tends to present with nonspecific manifestations,
      and fever is often absent. METHODS: This article is based on a systematic search
      of Medline and the Cochrane Library for the period January 2009 to March 2017. Of
      the 788 articles identified, 30 publications were considered. RESULTS: The goals
      of treatment for spondylodiscitis are to eliminate infection, restore
      functionality of the spine, and relieve pain. Magnetic resonance imaging (MRI)
      remains the gold standard for the radiological demonstration of this condition,
      with 92% sensitivity and 96% specificity. It also enables visualization of the
      spatial extent of the infection and of abscess formation (if present). The most
      common bacterial cause of spondylodiscitis in Europe is Staphylococcus aureus,
      but tuberculous spondylodiscitis is the most common type worldwide. Antibiotic
      therapy is a pillar of treatment for spondylodiscitis and should be a part of the
      treatment in all cases. Neurologic deficits, sepsis, an intraspinal empyema, the
      failure of conservative treatment, and spinal instability are all indications for
      surgical treatment. CONCLUSION: The quality of life of patients who have been
      appropriately treated for spondylodiscitis has been found to be highly
      satisfactory in general, although back pain often persists. The risk of
      recurrence increases in the presence of accompanying illnesses such as diabetes
      mellitus, renal failure, or undrained epidural abscesses.

PMID- 29321101
TI  - Bioremediation and detoxification of industrial wastes by earthworms:
      Vermicompost as powerful crop nutrient in sustainable agriculture.
AB  - Vermicompost is the final product of the vermicomposting process involving the
      collective action of earthworms and microbes. During this process, the waste is
      converted into useful manure by reducing the harmful effects of waste. Toxicity
      of industrial wastes is evaluated by plant bioassays viz. Allium cepa and Vicia
      faba test. These bioassays are sensitive and cost-effective for the monitoring of
      environmental contamination. The valorization potential of earthworms and their
      ability to detoxify heavy metals in industrial wastes is because of their strong
      metabolic system and involvement of earthworm gut microbes and chloragocyte
      cells. Most of the studies reported that the vermicompost produced from organic
      wastes contains higher amounts of humic substances, which plays a major role in
      growth of plants. The present article discusses the detoxification of industrial
      wastes by earthworms and the role of final vermicompost in plant growth and
      development.

PMID- 29321099
TI  - Non-Specific Low Back Pain.
AB  - BACKGROUND: For many years, low back pain has been both the leading cause of days
      lost from work and the leading indication for medical rehabilitation. The goal of
      the German Disease Management Guideline (NDMG) on nonspecific low back pain is to
      improve the treatment of patients with this condition. METHODS: The current
      update of the NDMG on non-specific low back pain is based on articles retrieved
      by a systematic search of the literature for systematic reviews. Its
      recommendations for diagnosis and treatment were developed by a collaborative
      effort of 29 scientific medical societies and organizations and approved in a
      formal consensus process. RESULTS: If the history and physical examination do not
      arouse any suspicion of a dangerous underlying cause, no further diagnostic
      evaluation is indicated for the time being. Passive, reactive measures should be
      taken only in combination with activating measures, or not at all. When drugs are
      used for symptomatic treatment, patients should be treated with the most suitable
      drug in the lowest possible dose and for as short a time as possible. CONCLUSION:
      A physician should be in charge of the overall care process. The patient should
      be kept well informed over the entire course of his or her illness and should be
      encouraged to adopt a healthful lifestyle, including regular physical exercise.

PMID- 29321102
TI  - A longitudinal study into the reciprocal effects of identities and smoking
      behaviour: Findings from the ITC Netherlands Survey.
AB  - OBJECTIVE: Although it has been found that identity constructs related to smoking
      are associated with changes in smoking behaviour, the direction of causal
      associations is as yet unclear. This study aims to clarify the nature and
      direction of these associations. METHODS: In this longitudinal study we examined
      the reciprocal relations between identity constructs (i.e., smoker self-identity,
      quitter self-identity and smoker group-identity), intention to quit and smoking
      and quitting behaviour among a sample of 1036 smokers and ex-smokers, using cross
      lagged structural equation modelling. Moreover, we tested whether these relations
      differed by socio-economic status (SES). RESULTS: Identity and smoking behaviour
      were reciprocally related in that in intention to quit and smoking behaviour
      consistently predicted identity change, and identity predicted (changes in)
      intentions to quit and smoking behaviour. Behaviour appears more important for
      identity change than identity for behaviour change. Furthermore, quitter self
      identity appears more important than smoker self- and group-identity.
      Relationships did not differ significantly between SES-groups. The findings were
      replicated using a cross-validation sample. CONCLUSION: Results imply that
      changing smoking behaviour may be a vehicle to change smoking-related identity.
      Moreover, strengthening identification with quitting is more crucial for quit
      success than decreasing smoker identities. The finding that behaviour may be more
      important for identity than vice versa, if replicated, may call for additions to
      identity theories.

PMID- 29321103
TI  - Does GRIN2B gene influence obsessive-compulsive disorder risk, symptom dimensions
      and treatment response?

PMID- 29321104
TI  - Neurectomy for anterior cutaneous nerve entrapment syndrome in children.
AB  - INTRODUCTION: Anterior cutaneous nerve entrapment syndrome (ACNES) is an
      underrecognized etiology of chronic abdominal pain that causes great morbidity to
      those affected. We sought to determine the outcome of neurectomy for ACNES in
      children. METHODS: Demographic and clinical data on children who underwent
      neurectomy for ACNES by a single surgeon from 10/2011 to 01/2017 were reviewed.
      RESULTS: Twenty-six patients underwent neurectomy for ACNES. Five were male and
      average age was 15years (10-21). Median (IQR) preoperative pain duration was 15
      (8-29) months and 19 reported their pain was 10/10 (6-10). Thirteen patients were
      taking antidepressants, 12 Gabapentin, and 4 narcotics. Most had been
      hospitalized at least once secondary to the pain. All 26 had undergone diagnostic
      studies including: nuclear medicine scan, fluoroscopy, computed tomography,
      magnetic resonance imaging, sonography, endoscopy and surgery. Once the diagnosis
      was suspected, all underwent at least one ultrasound-directed nerve block, which
      provided relief lasting from 6h to 14days. Patients then underwent outpatient
      surgery with division of the involved nerve(s). There were no perioperative
      complications. Most patients reported incisional discomfort for 3-14days
      afterward, and immediate resolution of the nerve pain without cutaneous numbness.
      Postoperatively, 15 patients (58%) were pain free long-term; pain recurred to a
      lesser severity in 8 (31%) and recurred to the same extent in 3 (11%), with
      average time to recurrence of 6.7months. Of those whose pain recurred to a lesser
      extent, all achieved long term relief, 4 improved with time, 1 through repeat
      neurectomy, 2 through medical treatment for underlying psychiatric disorders and
      1 through treatment for newly diagnosed inflammatory bowel disease. Of those
      children with pain recurring to the same extent, all underwent repeat neurectomy,
      none of whom achieved pain relief. CONCLUSION: ACNES should be considered in
      children with chronic abdominal pain. Neurectomy is safe and relieves pain in
      around 88% of selected children. Further investigation is necessary to optimize
      patient selection. LEVEL OF EVIDENCE: IV.

PMID- 29321105
TI  - The Use of Near Infrared Spectroscopy to Assess Infant Pain.

PMID- 29321106
TI  - Segway(r) Personal Transporter-Related Injuries: A Systematic Literature Review
      and Implications for Acute and Emergency Care.
AB  - BACKGROUND: The Segway(r) Personal TransporterTM (SPT) is used widely as a means
      of transport for city sightseeing tours, law enforcement, and professionals
      working in large facilities and factories. METHODS: We conducted a systematic
      review of the literature to assess SPT-related injuries. Following the PRISMA
      (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines,
      we queried PubMed from 1990 to 2017. The search terms Segway, personal
      transporter, and injury were used. Only English-language studies were included.
      Data were extracted from each article, specifically the sample size, study
      setting, and design, as well as the prevalence of specific injuries. RESULTS: A
      total of six articles were included that included data on 135 patients. Sample
      size per study varied from 1 to 41 patients. Studies occurred in both the
      emergency department and inpatient settings, including medical-surgical wards,
      and intensive care units. The most commonly reported injuries were orthopedic
      cases (n = 45), maxillofacial cases (n = 13), neurologic cases (n = 8), and
      thoracic cases (n = 10). CONCLUSIONS: The SPT is an innovative transportation
      method; however, its use is associated with a wide range of injuries. Many of
      these injuries require hospital admission and surgical intervention, incurring
      significant morbidity and high costs.

PMID- 29321107
TI  - Can I Send This Patient with Stroke Home? Strategies Managing Transient Ischemic
      Attack and Minor Stroke in the Emergency Department.
AB  - BACKGROUND: While transient ischemic attack and minor stroke (TIAMS) are common
      conditions evaluated in the emergency department (ED), there is controversy
      regarding the most effective and efficient strategies for managing them in the
      ED. Some patients are discharged after evaluation in the ED and cared for in the
      outpatient setting, while others remain in an observation unit without being
      admitted or discharged, and others experience prolonged and potentially costly
      inpatient admissions. OBJECTIVE OF THE REVIEW: The goal of this clinical review
      was to summarize and present recommendations regarding the disposition of TIAMS
      patients in the ED (e.g., admission vs. discharge). DISCUSSION: An estimated
      250,000 to 300,000 TIA events occur each year in the United States, with an
      estimated near-term risk of subsequent stroke ranging from 3.5% to 10% at 2 days,
      rising to 17% by 90 days. While popular and easy to use, reliance solely on risk
      stratification tools, such as the ABCD2, should not be used to determine whether
      TIAMS patients can be discharged safely. Additional vascular imaging and advanced
      brain imaging may improve prediction of short-term neurologic risk. We also
      review various disposition strategies (e.g., inpatient vs. outpatient/ED
      observation units) with regard to their association with neurologic outcomes,
      such as 30-day or 90-day stroke recurrence or new stroke, in addition to other
      outcomes, such as hospital length of stay and health care costs. CONCLUSIONS:
      Discharge from the ED for rapid outpatient follow-up may be a safe and effective
      strategy for some forms of minor stroke without disabling deficit and TIA
      patients after careful evaluation and initial ED workup. Future research on such
      strategies has the potential to improve neurologic and overall patient outcomes
      and reduce hospital costs and ED length of stay.

PMID- 29321109
TI  - How artificial intelligence could transform emergency department operations.

PMID- 29321110
TI  - Freestanding emergency department visits and disasters: The case of Hurricane
      Harvey.

PMID- 29321108
TI  - Surgical stabilization for first-time shoulder dislocators: a multicenter
      analysis.
AB  - BACKGROUND: Anterior shoulder dislocations in young patients are associated with
      high rates of recurrent instability. Although some surgeons advocate for surgical
      stabilization after a single dislocation event in this population, there is
      sparse research evaluating surgical treatment for first-time dislocators.
      METHODS: Patients undergoing surgical stabilization for anterior shoulder
      instability were prospectively enrolled at multiple institutions from 2015-2017
      and stratified by number of dislocations before surgery. Demographic data,
      preoperative patient-reported outcomes, imaging findings, surgical findings, and
      procedures performed were compared between groups. Analysis of variance, chi2,
      and multivariate logistic regression were used for statistical analysis. RESULTS:
      The study included 172 patients (mean age, 25.3 years; 79.1% male patients) for
      analysis (58 patients with 1 dislocation, 69 with 2-5 dislocations, 45 with >5
      dislocations). There were no intergroup differences in demographic
      characteristics, preoperative patient-reported outcomes, or physical examination
      findings. Preoperative imaging revealed increased glenoid bone loss in patients
      with multiple dislocation events (P = .043). Intraoperatively, recurrent
      dislocators were more likely to have bony Bankart lesions (odds ratio [OR], 3.26;
      P = .024) and biceps pathology (OR, 6.27; P = .013). First-time dislocators more
      frequently underwent arthroscopic Bankart repair and/or capsular plication (OR,
      2.22; P = .016), while recurrent dislocators were more likely to undergo open
      Bristow-Latarjet procedures (OR, 2.80; P = .049) and surgical treatment for
      biceps pathology (OR, 5.03; P = .032). CONCLUSIONS: First-time shoulder
      dislocators who undergo stabilization are more likely to undergo an arthroscopic
      procedure and less likely to have bone loss or biceps pathology compared with
      recurrent dislocators. Future studies are needed to ascertain long-term outcomes
      of surgical stabilization based on preoperative dislocation events.

PMID- 29321111
TI  - A systematic review of the pain scales in adults: Which to use?
AB  - OBJECTIVE: The study analysed the Visual Analogue Scale (VAS), the Verbal Rating
      Scale (VRS) and the Numerical Rating Scale (NRS) to determine: 1. Were the
      compliance and usability different among scales? 2. Were any of the scales
      superior over the other(s) for clinical use? METHODS: A systematic review of
      currently published studies was performed following standard guidelines. Online
      database searches were performed for clinical trials published before November
      2017, on the comparison of the pain scores in adults and preferences of the
      specific patient groups. A literature search via electronic databases was carried
      out for the last fifteen years on English Language papers. The search terms
      initially included pain rating scales, pain measurement, pain intensity, VAS,
      VRS, and NRS. Papers were examined for methodological soundness before being
      included. Data were independently extracted by two blinded reviewers. Studies
      were also assessed for bias using the Cochrane criteria. RESULTS: The initial
      data search yielded 872 potentially relevant studies; of these, 853 were excluded
      for some reason. The main reason for exclusion (33.7%) was that irrelevance to
      comparison of pain scales and scores, followed by pediatric studies (32.1%).
      Finally, 19 underwent full-text review, and were analysed for the study purposes.
      Studies were of moderate (n=12, 63%) to low (n=7, 37%) quality. CONCLUSIONS: All
      three scales are valid, reliable and appropriate for use in clinical practice,
      although the VAS is more difficulties than the others. For general purposes the
      NRS has good sensitivity and generates data that can be analysed for audit
      purposes.

PMID- 29321112
TI  - The evaluation and management of urolithiasis in the ED: A review of the
      literature.
AB  - BACKGROUND: Urolithiasis is a common condition in the U.S. Patients frequently
      present to the emergency department (ED) for care, including analgesia and
      treatments to facilitate stone passage. OBJECTIVE: With the new evidence
      concerning the evaluation and treatment of urolithiasis, this review summarizes
      current literature regarding the ED management of urolithiasis. DISCUSSION:
      Urolithiasis occurs primarily through supersaturation of urine and commonly
      presents with flank pain, hematuria, and nausea/vomiting. History, examination,
      and assessment with several laboratory tests are cornerstones of evaluation.
      Urinalysis is not diagnostic, but it may be used in association with other
      assessments. Risk assessment tools and advanced imaging can assist with
      diagnosis. Computed tomography (CT) is often considered the gold standard. Newer
      low-dose CT imaging may reduce radiation. Recent studies support ultrasound as an
      alternate diagnostic modality, especially in pediatric and pregnant patients.
      Nonsteroidal anti-inflammatory drugs remain first-line therapy, with opioids or
      intravenous lidocaine reserved for refractory pain. Tamsulosin can increase
      passage in larger stones but has not demonstrated benefit in smaller stones.
      Nifedipine and intravenous fluids are not recommended to facilitate passage.
      Surgical intervention is based upon stone size, duration, and modifying factors.
      Patients who are discharged should be advised on dietary changes. CONCLUSION:
      Urolithiasis is a common disease increasing in prevalence with the potential for
      significant morbidity. Focused evaluation with history, examination, and testing
      is important in diagnosis and management. Understanding the clinical features,
      risk assessment tools, imaging options, and treatment options can assist
      emergency physicians in the management of urolithiasis.

PMID- 29321113
TI  - Top-cited publications on point-of-care ultrasound: The evolution of research
      trends.
AB  - STUDY OBJECTIVES: Point-of-care ultrasound (POCUS) has been a rapidly growing and
      broadly used modality in recent decades. The purpose of this study was to
      determine how POCUS is incorporated into clinical medicine by analyzing trends of
      use in the published literature. METHODS: POCUS-related publications were
      retrieved from the Web of Science (WoS) database. The search results were ranked
      according to the number of times an article was cited during three time frames
      and average annual number of citations. Of the top 100 most cited publications in
      the four rankings, information regarding the publication journal, publication
      year, first author's nationality, field of POCUS application, and number of times
      the article was cited was recorded for trend analysis. RESULTS: A total of 7860
      POCUS-related publications were retrieved, and publications related to POCUS
      increased from 8 in 1990 to 754 in 2016. The top 148 cited publications from the
      four ranking groups were included in this study. Trauma was the leading
      application field in which POCUS was studied prior to 2001. After 2004, thorax,
      cardiovascular, and procedure-guidance were the leading fields in POCUS research.
      >79% (118/148) of the top-cited publications were conducted by authors in the
      United States, Italy, and France. The majority of publications were published in
      critical care medicine and emergency medicine journals. CONCLUSIONS: In recent
      years, publications relating to POCUS have increased. POCUS-related research has
      mainly been performed in thorax, cardiovascular, and procedure-guidance
      ultrasonography fields, replacing trauma as the major field in which POCUS was
      previously studied.

PMID- 29321114
TI  - Nebulized ketamine to avoid mechanical ventilation in a pediatric patient with
      severe asthma exacerbation.
AB  - Asthma is a major cause of morbidity and mortality despite advances in outpatient
      treatment. Sometimes, children fail to respond to standard treatment and can
      potentially require mechanical ventilation. We describe a case of a 26-month-old
      girl with a severe asthma exacerbation successfully managed by ketamine
      administration via nebulization route that permitted to avoid mechanical
      ventilation. Nebulized ketamine might be a reasonable option to avoid mechanical
      ventilation in children who fail to respond to standard treatment of severe
      asthma exacerbation.

PMID- 29321115
TI  - Trauma patients presenting with a King laryngeal tubeTM in place can be safely
      intubated in the emergency department.

PMID- 29321116
TI  - All eye complaints are not created equal: The value of hand-held retina camera in
      the Emergency Department.

PMID- 29321117
TI  - Emergency department resuscitation of pediatric trauma patients in Iraq and
      Afghanistan.
AB  - BACKGROUND: Military hospital healthcare providers treated children during the
      recent conflicts in Afghanistan and Iraq. Compared to adults, pediatric patients
      present unique challenges during trauma resuscitations and have notably been
      discussed in few research reports. We seek to describe ED interventions performed
      on pediatric trauma patients in Iraq and Afghanistan. METHODS: We queried the
      Department of Defense Trauma Registry (DODTR) for all pediatric patients in Iraq
      and Afghanistan from January 2007 to January 2016. Subjects were grouped based on
      Centers for Disease Control age categories. We used descriptive statistics.
      RESULTS: During this period, there were 3388 pediatric encounters that arrived at
      the ED with signs of life or on-going interventions. Most subjects were male
      (77.2%), located in Afghanistan (67.9%), injured by explosive (43.2%), and
      admitted to an intensive care unit (57.8%). Most of those arriving to the ED
      alive or with on-going interventions survived to hospital discharge (91.6%). The
      most frequently encountered age group was 5-9years (33.3%) followed by 10-14years
      (31.5%). The most common interventions were vascular access (86.6%), fluid
      administration (85.0%), and external warming (44.6%). Intubation was the most
      frequent airway intervention (18.2%). Packed red blood cells were the most
      frequently administered blood product (33.8% of subjects). CONCLUSIONS: Pediatric
      subjects accounted for a notable portion of care delivered in theater emergency
      departments during the study period. Vascular access and fluid administration
      were the most frequently performed interventions. Pediatric-specific training is
      needed as a part of deployment medicine operations.

PMID- 29321118
TI  - A comparison of carotid doppler ultrasonography and capnography in evaluating the
      efficacy of CPR.
AB  - INTRODUCTION AND PURPOSE: The end-tidal carbon dioxide (ETCO2) measurement is
      accepted as the gold standard method for assessing cardiopulmonary resuscitation
      (CPR) efficacy. In recent studies, the use of Carotid Doppler Ultrasonography has
      become widespread in showing CPR efficacy. In the present study, the carotid
      blood flow measurement was compared with ETCO2 measurement and an evaluation was
      made of whether this method could be used as an alternative method to capnography
      in the assessment of CPR efficacy. MATERIAL AND METHOD: This study was conducted
      on patients who presented at the Emergency Department (ED) with non-traumatic
      arrest or began to suffer from arrest during emergency service follow-up. The
      main carotid artery peak systolic velocity (PSV), end diastolic velocity (EDV)
      and time-dependent mean flow velocity (MNV), and ETCO2 values were measured and
      recorded after the 100th chest pressure of the CPR cycle and the results were
      statistically analyzed. RESULTS: The mean age of the patients was 54.5+/
      12.3years and 65.6% of the patients were male. The mean values of patients
      measured from the carotid artery during the CPR were PSV 67.1+/-17.3, EDV 16.3+/
      4.5, MNV 25.5+/-8.1 and ETCO2 22.2+/-8.1. A significant difference was found
      between in-hospital and out-of-hospital arrests in terms of patient outcome
      (return of spontaneous circulation (ROSC) and death) (p<0.05). The mean ETCO2
      values of those who died were found to be lower than those of the ROSC group
      (p<0.05). Although there was a positive and low-level of correlation between the
      ETCO2 values and PSV values, and a positive and very low-level of correlation
      between the EDV and MNV values of all patients, these correlations were not
      statistically significant. (p>0.05). CONCLUSION: A low correlation was found
      between the PSV and ETCO2 values. With effective CPR, the results close to
      carotid blood flow in normal healthy individuals were obtained. However, the
      study showed that carotid blood flow measurement results during CPR were not as
      valuable as ETCO2 in demonstrating CPR efficacy.

PMID- 29321119
TI  - Treatment and resources for patients with non-occupational HIV exposure
      presenting to the emergency department.

PMID- 29321120
TI  - Evaluating vancomycin and piperacillin-tazobactam in ED patients with severe
      sepsis and septic shock.
AB  - STUDY OBJECTIVE: To determine the frequency and cause of inadequate initial
      antibiotic therapy with vancomycin and piperacillin-tazobactam in patients with
      severe sepsis and septic shock in the emergency department (ED), characterize its
      impact on patient outcomes, and identify patients who would benefit from an
      alternative initial empiric regimen. METHODS: Retrospective cohort study
      conducted between 2012 and 2015 in which 342 patients with culture-positive
      severe sepsis or septic shock who received initial vancomycin and piperacillin
      tazobactam were reviewed to determine appropriateness of antimicrobial therapy,
      risk factors for inappropriate use, and outcome data. Univariate and multivariate
      regression analyses were determined to identify associations between
      inappropriate antibiotic use and outcomes and to identify risk factors that may
      predict which patients would benefit from an alternative initial regimen.
      RESULTS: Vancomycin and piperacillin-tazobactam were inappropriate for 24% of
      patients with severe sepsis or septic shock, largely due to non-susceptible
      infections, particularly ESBL organisms and Clostridium difficile. Risk factors
      included multiple sources of infection (OR 4.383), admission from a skilled
      nursing facility (OR 3.763), a history of chronic obstructive pulmonary disease
      (COPD) (OR 3.175), intra-abdominal infection (OR 2.890), and immunosuppression
      (OR 1.930). We did not find a mortality impact. CONCLUSION: Vancomycin and
      piperacillin-tazobactam were an inappropriate antibiotic combination for
      approximately 24% of patients with either severe sepsis or septic shock in the
      ED. Patients with known COPD, residence at a skilled nursing facility, a history
      concerning for Clostridium difficile, and immunosuppression would benefit from an
      alternative regimen. Future prospective studies are needed to validate these
      findings.

PMID- 29321121
TI  - Seizure Prediction Is Possible-Now Let's Make It Practical.

PMID- 29321122
TI  - Technology-Assisted Behavioral Intervention to Extend Sleep Duration: Development
      and Design of the Sleep Bunny Mobile App.
AB  - BACKGROUND: Despite the high prevalence of short sleep duration (29.2% of adults
      sleep <6 hours on weekdays), there are no existing theory-based behavioral
      interventions to extend sleep duration. The popularity of wearable sleep trackers
      provides an opportunity to engage users in interventions. OBJECTIVE: The
      objective of this study was to outline the theoretical foundation and iterative
      process of designing the "Sleep Bunny," a technology-assisted sleep extension
      intervention including a mobile phone app, wearable sleep tracker, and brief
      telephone coaching. We conducted a two-step process in the development of this
      intervention, which was as follows: (1) user testing of the app and (2) a field
      trial that was completed by 2 participants with short sleep duration and a
      cardiovascular disease risk factor linked to short sleep duration (body mass
      index [BMI] >25). METHODS: All participants had habitual sleep duration <6.5
      hours verified by 7 days of actigraphy. A total of 6 individuals completed
      initial user testing in the development phase, and 2 participants completed field
      testing. Participants in the user testing and field testing responded to open
      ended surveys about the design and utility of the app. Participants in the field
      testing completed the Epworth Sleepiness Scale and also wore an actigraph for a 1
      week baseline period and during the 4-week intervention period. RESULTS: The
      feedback suggests that users enjoyed the wearable sleep tracker and found the app
      visually pleasing, but they suggested improvements to the notification and
      reminder features of the app. The 2 participants who completed the field test
      demonstrated significant improvements in sleep duration and daytime sleepiness.
      CONCLUSIONS: Further testing is needed to determine effects of this intervention
      in populations at risk for the mental and physical consequences of sleep loss.

PMID- 29321123
TI  - Comparative Analysis of Women With Notable Subjective Health Indicators Compared
      With Participants in the Australian Longitudinal Study on Women's Health: Cross
      Sectional Survey.
AB  - BACKGROUND: At least six communities with unusually good health and longevity
      have been identified, but their lifestyles aren't adopted widely. Informal
      evidence suggests that women associated with Universal Medicine (UM), a
      complementary medicine health care organization in Eastern Australia and the
      United Kingdom with normal lifestyles, also have several unusual health
      indicators. OBJECTIVE: Our objective was to determine how UM participants
      compared with women in the Australian population at large on a variety of health
      indicators. METHODS: In an Internet survey conducted July to September 2015, a
      total of 449 female UM participants from 15 countries responded to 43 health
      indicator questions taken from the Australian Longitudinal Study on Women's
      Health (ALSWH). RESULTS: Survey responses revealed large positive differences in
      mental and physical health when compared with the ALSWH respondents, except for
      abnormal Pap test and low iron history. Differences and corresponding effect size
      estimates (Cohen d; >=0.8 is a high difference, >=0.5 a medium and >=0.2 a small
      one with P<.001 except where indicated) included body mass index (BMI; 1.11),
      stress level (0.20, P=.006), depression (0.44), summary physical (0.31) and
      mental health (0.37), general mental health (0.39), emotional (0.15, P=.009) and
      social functioning (0.22), vitality (0.58), and general health (0.49), as well as
      lower incidences of diabetes, hypertension, and thrombosis (P<.001 each). Neither
      education levels nor country of residence had predictive value. Neither education
      levels nor country of residence had predictive value. Age did not predict BMI.
      CONCLUSIONS: The women's responses notably claim substantially lower levels of
      illness and disease than in the general Australian population. TRIAL
      REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR):
      ACTRN12617000972325; https://www.anzctr.
      org.au/Trial/Registration/TrialReview.aspx?id=373120&isReview=true (Archived by
      WebCite at http://www.webcitation.org/ 6wEDDn45O).

PMID- 29321124
TI  - Hearing Tests Based on Biologically Calibrated Mobile Devices: Comparison With
      Pure-Tone Audiometry.
AB  - BACKGROUND: Hearing screening tests based on pure-tone audiometry may be
      conducted on mobile devices, provided that the devices are specially calibrated
      for the purpose. Calibration consists of determining the reference sound level
      and can be performed in relation to the hearing threshold of normal-hearing
      persons. In the case of devices provided by the manufacturer, together with
      bundled headphones, the reference sound level can be calculated once for all
      devices of the same model. OBJECTIVE: This study aimed to compare the hearing
      threshold measured by a mobile device that was calibrated using a model-specific,
      biologically determined reference sound level with the hearing threshold obtained
      in pure-tone audiometry. METHODS: Trial participants were recruited offline using
      face-to-face prompting from among Otolaryngology Clinic patients, who own Android
      based mobile devices with bundled headphones. The hearing threshold was obtained
      on a mobile device by means of an open access app, Hearing Test, with
      incorporated model-specific reference sound levels. These reference sound levels
      were previously determined in uncontrolled conditions in relation to the hearing
      threshold of normal-hearing persons. An audiologist-assisted self-measurement was
      conducted by the participants in a sound booth, and it involved determining the
      lowest audible sound generated by the device within the frequency range of 250 Hz
      to 8 kHz. The results were compared with pure-tone audiometry. RESULTS: A total
      of 70 subjects, 34 men and 36 women, aged 18-71 years (mean 36, standard
      deviation [SD] 11) participated in the trial. The hearing threshold obtained on
      mobile devices was significantly different from the one determined by pure-tone
      audiometry with a mean difference of 2.6 dB (95% CI 2.0-3.1) and SD of 8.3 dB
      (95% CI 7.9-8.7). The number of differences not greater than 10 dB reached 89%
      (95% CI 88-91), whereas the mean absolute difference was obtained at 6.5 dB (95%
      CI 6.2-6.9). Sensitivity and specificity for a mobile-based screening method were
      calculated at 98% (95% CI 93-100.0) and 79% (95% CI 71-87), respectively.
      CONCLUSIONS: The method of hearing self-test carried out on mobile devices with
      bundled headphones demonstrates high compatibility with pure-tone audiometry,
      which confirms its potential application in hearing monitoring, screening tests,
      or epidemiological examinations on a large scale.

PMID- 29321125
TI  - Efficacy of a Web-Based Safety Decision Aid for Women Experiencing Intimate
      Partner Violence: Randomized Controlled Trial.
AB  - BACKGROUND: Intimate partner violence (IPV) is a human rights violation and
      leading health burden for women. Safety planning is a hallmark of specialist
      family violence intervention, yet only a small proportion of women access formal
      services. A Web-based safety decision aid may reach a wide audience of women
      experiencing IPV and offer the opportunity to prioritize and plan for safety for
      themselves and their families. OBJECTIVE: The aim of this study was to test the
      efficacy of a Web-based safety decision aid (isafe) for women experiencing IPV.
      METHODS: We conducted a fully automated Web-based two-arm parallel randomized
      controlled trial (RCT) in a general population of New Zealand women who had
      experienced IPV in the past 6 months. Computer-generated randomization was based
      on a minimization scheme with stratification by severity of violence and
      children. Women were randomly assigned to the password-protected intervention
      website (safety priority setting, danger assessment, and tailored action plan
      components) or control website (standard, nonindividualized information). Primary
      endpoints were self-reported mental health (Center for Epidemiologic Studies
      Depression Scale-Revised, CESD-R) and IPV exposure (Severity of Violence Against
      Women Scale, SVAWS) at 12-month follow-up. Analyses were by intention to treat.
      RESULTS: Women were recruited from September 2012 to September 2014. Participants
      were aged between 16 and 60 years, 27% (111/412) self-identified as Maori
      (indigenous New Zealand), and 51% (210/412) reported at baseline that they were
      unsure of their future plans for their partner relationship. Among the 412 women
      recruited, retention at 12 months was 87%. The adjusted estimated intervention
      effect for SVAWS was -12.44 (95% CI -23.35 to -1.54) for Maori and 0.76 (95% CI 
      5.57 to 7.09) for non-Maori. The adjusted intervention effect for CESD-R was 
      7.75 (95% CI -15.57 to 0.07) for Maori and 1.36 (-3.16 to 5.88) for non-Maori. No
      study-related adverse events were reported. CONCLUSIONS: The interactive,
      individualized Web-based isafe decision aid was effective in reducing IPV
      exposure limited to indigenous Maori women. Discovery of a treatment effect in a
      population group that experiences significant health disparities is a welcome,
      important finding. TRIAL REGISTRATION: Australian New Zealand Clinical Trials
      Registry (ANZCTR): ACTRN12612000708853;
      https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=1261200070885
      (Archived by Webcite at http://www.webcitation/61MGuVXdK).

PMID- 29321126
TI  - Toward mHealth Brief Contact Interventions in Suicide Prevention: Case Series
      From the Suicide Intervention Assisted by Messages (SIAM) Randomized Controlled
      Trial.
AB  - BACKGROUND: Research indicates that maintaining contact either via letter or
      postcard with at-risk adults following discharge from care services after a
      suicide attempt (SA) can reduce reattempt risk. Pilot studies have demonstrated
      that interventions using mobile health (mHealth) technologies are feasible in a
      suicide prevention setting. OBJECTIVE: The aim of this study was to report three
      cases of patients recruited in the Suicide Intervention Assisted by Messages
      (SIAM) study to describe how a mobile intervention may influence follow-up.
      METHODS: SIAM is a 2-year, multicenter randomized controlled trial conducted by
      the Brest University Hospital, France. Participants in the intervention group
      receive SIAM text messages 48 hours after discharge, then at day 8 and day 15,
      and months 1, 2, 3, 4, 5, and 6. The study includes participants aged 18 years or
      older, who have attended a participating hospital for an SA, and have been
      discharged from the emergency department (ED) or a psychiatric unit (PU) for a
      stay of less than 7 days. Eligible participants are randomized between the SIAM
      intervention messages and a control group. In this study, we present three cases
      from the ongoing SIAM study that demonstrate the capability of a mobile-based
      brief contact intervention for triggering patient-initiated contact with a crisis
      support team at various time points throughout the mobile-based follow-up period.
      RESULTS: Out of the 244 patients recruited in the SIAM randomized controlled
      trial, three cases were selected to illustrate the impact of mHealth on suicide
      risk management. Participants initiated contact with the emergency crisis support
      service after receiving text messages up to 6 months following discharge from the
      hospital. Contact was initiated immediately following receipt of a text message
      or up to 6 days following a message. CONCLUSIONS: This text message-based brief
      contact intervention has demonstrated the potential to reconnect suicidal
      individuals with crisis support services while they are experiencing suicidal
      ideation as well as in a period after receiving messages. As follow-up phone
      calls over an extended period of time may not be feasible, this intervention has
      the potential to offer simple technological support for individuals following
      discharge from the ED. TRIAL REGISTRATION: ClinicalTrials.gov NCT02106949;
      https://clinicaltrials.gov/ct2/show/NCT02106949 (Archived by WebCite at
      http://www.webcitation.org/6wMtAFL49).

PMID- 29321128
TI  - Measurement of Lipoprotein-Associated Phospholipase A2 by Use of 3 Different
      Methods: Exploration of Discordance between ELISA and Activity Assays.
AB  - BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA2), an enzyme
      associated with inflammation, is used as a biomarker for cardiovascular disease
      risk. Both the concentration and activity of Lp-PLA2 have been shown to be
      clinically relevant. However, there is a discordance between the serum
      concentration of Lp-PLA2 measured by the standard ELISA-based immunoassays and
      the activity of this enzyme, leading to substantial discordance in risk
      categorization depending on assay format. METHODS: We developed 2 LC-MS/MS-based
      assays to quantify serum Lp-PLA2 activity (multiple reaction monitoring detection
      of product) and concentration [stable isotope standards and capture by
      antipeptide antibody (SISCAPA) immunoaffinity], and we investigated their
      correlation to commercially offered colorimetric activity and immunometric
      concentrations assays. Associations between Lp-PLA2 and lipoproteins and the
      effect of selected detergents in liberating Lp-PLA2 were evaluated by use of
      immunoprecipitation and Western blot analyses. RESULTS: Serum Lp-PLA2
      concentrations measured by quantitative SISCAPA-mass spectrometry were
      substantially higher than concentrations typically measured by immunoassay and
      showed an improved agreement with Lp-PLA2 activity. With detergents, liberation
      of Lp-PLA2 from lipoprotein complexes dramatically increased the amount of
      protein detected by immunoassay and improved the agreement with activity
      measurements. CONCLUSIONS: Quantitative analysis of Lp-PLA2 concentration and
      activity by LC-MS/MS assays provided key insight into resolving the well
      documented discordance between Lp-PLA2 concentration (determined by immunoassay)
      and activity. Quantitative detection of Lp-PLA2 by immunoassay appears to be
      strongly inhibited by interaction of Lp-PLA2 with lipoprotein. Together, the
      results illustrate the advantages of quantitative LC-MS/MS for measurement of Lp
      PLA2 concentration (by SISCAPA) and activity (by direct product detection).

PMID- 29321127
TI  - Effectiveness of a Technology-Based Supportive Educational Parenting Program on
      Parental Outcomes in Singapore: Protocol for a Randomized Controlled Trial.
AB  - BACKGROUND: Supportive educational programs during the perinatal period are
      scarce in Singapore. There is no continuity of care available in terms of support
      from community care nurses in Singapore. Parents are left on their own most of
      the time, which results in a stressful transition to parenthood. There is a need
      for easily accessible technology-based educational programs that can support
      parents during this crucial perinatal period. OBJECTIVE: The aim of this study
      was to describe the study protocol of a randomized controlled trial on a
      technology-based supportive educational parenting program. METHODS: A randomized
      controlled two-group pretest and repeated posttest experimental design will be
      used. The study will recruit 118 parents (59 couples) from the antenatal clinics
      of a tertiary public hospital in Singapore. Eligible parents will be randomly
      allocated to receive either the supportive educational parenting program or
      routine perinatal care from the hospital. Outcome measures include parenting self
      efficacy, parental bonding, postnatal depression, social support, parenting
      satisfaction, and cost evaluation. Data will be collected at the antenatal
      period, immediate postnatal period, and at 1 month and 3 months post childbirth.
      RESULTS: Recruitment of the study participants commenced in December 2016 and is
      still ongoing. Data collection is projected to finish within 12 months, by
      December 2017. CONCLUSIONS: This study will identify a potentially clinically
      useful, effective, and cost-effective supportive educational parenting program to
      improve parental self-efficacy and bonding in newborn care, which will then
      improve parents' social support-seeking behaviors, emotional well-being, and
      satisfaction with parenting. It is hoped that better supported and satisfied
      parents will consider having more children, which may in turn influence
      Singapore's ailing birth rate. TRIAL REGISTRATION: International Standard
      Randomized Controlled Trial Number (ISRCTN): 48536064;
      https://www.isrctn.com/ISRCTN48536064 (Archived by WebCite at
      http://www.webcitation.org/6wMuEysiO).

PMID- 29321130
TI  - Exercise Hemodynamic and Functional Capacity After Mitral Valve Replacement in
      Patients With Ischemic Mitral Regurgitation: A Comparison of Mechanical Versus
      Biological Prostheses.
AB  - BACKGROUND: In patients with ischemic mitral regurgitation requiring mitral valve
      replacement (MVR), the choice of the prosthesis type is crucial. The exercise
      hemodynamic and functional capacity performance in patients with contemporary
      prostheses have never been investigated. To compare exercise hemodynamic and
      functional capacity between biological (MVRb) and mechanical (MVRm) prostheses.
      METHODS AND RESULTS: We analyzed 86 consecutive patients with ischemic mitral
      regurgitation who underwent MVRb (n=41) or MVRm (n=45) and coronary artery bypass
      grafting. All patients underwent preoperative resting echocardiography and 6
      minute walking test. At follow-up, exercise stress echocardiography was
      performed, and the 6-minute walking test was repeated. Resting and exercise
      indexed effective orifice areas of MVRm were larger when compared with MVRb
      (resting: 1.30+/-0.2 versus 1.19+/-0.3 cm2/m2; P=0.03; exercise: 1.57+/-0.2
      versus 1.18+/-0.3 cm2/m2; P=0.0001). The MVRm had lower exercise systolic
      pulmonary arterial pressure at follow-up compared with MVRb (41+/-5 versus 59+/-7
      mm Hg; P=0.0001). Six-minute walking test distance was improved in the MVRm (pre
      operative: 242+/-43, post-operative: 290+/-50 m; P=0.001), whereas it remained
      similar in the MVRb (pre-operative: 250+/-40, post-operative: 220+/-44 m;
      P=0.13). In multivariable analysis, type of prosthesis, exercise indexed
      effective orifice area, and systolic pulmonary arterial pressure were joint
      predictors of change in 6-minute walking test (ie, difference between baseline
      and follow-up). CONCLUSIONS: In patients with ischemic mitral regurgitation,
      bioprostheses are associated with worse hemodynamic performance and reduced
      functional capacity, when compared with MVRm. Randomized studies with longer
      follow-up including quality of life and survival data are required to confirm
      these results.

PMID- 29321129
TI  - Novel Reversible Model of Atherosclerosis and Regression Using Oligonucleotide
      Regulation of the LDL Receptor.
AB  - RATIONALE: Animal models have been used to explore factors that regulate
      atherosclerosis. More recently, they have been used to study the factors that
      promote loss of macrophages and reduction in lesion size after lowering of plasma
      cholesterol levels. However, current animal models of atherosclerosis regression
      require challenging surgeries, time-consuming breeding strategies, and methods
      that block liver lipoprotein secretion. OBJECTIVE: We sought to develop a more
      direct or time-effective method to create and then reverse hypercholesterolemia
      and atherosclerosis via transient knockdown of the hepatic LDLR (low-density
      lipoprotein receptor) followed by its rapid restoration. METHODS AND RESULTS: We
      used antisense oligonucleotides directed to LDLR mRNA to create
      hypercholesterolemia in wild-type C57BL/6 mice fed an atherogenic diet. This led
      to the development of lesions in the aortic root, aortic arch, and
      brachiocephalic artery. Use of a sense oligonucleotide replicating the targeted
      sequence region of the LDLR mRNA rapidly reduced circulating cholesterol levels
      because of recovery of hepatic LDLR expression. This led to a decrease in
      macrophages within the aortic root plaques and brachiocephalic artery, that is,
      regression of inflammatory cell content, after a period of 2 to 3 weeks.
      CONCLUSIONS: We have developed an inducible and reversible hepatic LDLR knockdown
      mouse model of atherosclerosis regression. Although cholesterol reduction
      decreased early en face lesions in the aortic arches, macrophage area was reduced
      in both early and late lesions within the aortic sinus after reversal of
      hypercholesterolemia. Our model circumvents many of the challenges associated
      with current mouse models of regression. The use of this technology will
      potentially expedite studies of atherosclerosis and regression without use of
      mice with genetic defects in lipid metabolism.

PMID- 29321132
TI  - Intersection of Pulmonary Hypertension and Right Ventricular Dysfunction in
      Patients on Left Ventricular Assist Device Support: Is There a Role for Pulmonary
      Vasodilators?
AB  - Left ventricular assist devices (LVADs) improve survival and quality of life in
      patients with advanced heart failure. Despite these benefits, combined post- and
      precapillary pulmonary hypertension can be particularly problematic in patients
      on LVAD support, often exacerbating right ventricular (RV) dysfunction. Both
      persistently elevated pulmonary vascular resistance and RV dysfunction are
      associated with adverse outcomes, including death after LVAD. These observations
      have led to significant interest in the use of pulmonary vasodilators to treat
      pulmonary hypertension and preserve RV function among LVAD-supported patients.
      Although pulmonary vasodilators are commonly used for the treatment of pulmonary
      hypertension and RV dysfunction in LVADs, the benefits of this practice remain
      unclear. The purpose of this review is to highlight the current challenges in
      managing pulmonary vascular disease and RV dysfunction in patients with heart
      failure on LVAD support.

PMID- 29321131
TI  - Efficacy of Ranolazine in Patients With Symptomatic Hypertrophic Cardiomyopathy:
      The RESTYLE-HCM Randomized, Double-Blind, Placebo-Controlled Study.
AB  - BACKGROUND: The late sodium current inhibitor ranolazine reverses the main
      electrophysiological and mechanical abnormalities of human hypertrophic
      cardiomyopathy (HCM) cardiomyocytes in vitro, suggesting potential clinical
      benefit. We aimed to assess the effect of ranolazine on functional capacity,
      symptomatic status, diastolic function, and arrhythmias in HCM. METHODS AND
      RESULTS: In this multicenter, double-blind, phase 2 study, 80 adult patients with
      nonobstructive HCM (age 53+/-14 years, 34 women) were randomly assigned to
      placebo (n=40) or ranolazine 1000 mg bid (n=40) for 5 months. The primary end
      point was change in peak VO2 compared with baseline using cardiopulmonary
      exercise test. Echocardiographic lateral and septal E/E' ratio, prohormone brain
      natriuretic peptide levels, 24-hour Holter arrhythmic profile, and quality of
      life were assessed. Ranolazine was safe and well tolerated. Overall, there was no
      significant difference in VO2 peak change at 5 months in the ranolazine versus
      placebo group (delta 0.15+/-3.96 versus -0.02+/-4.25 mL/kg per minute; P=0.832).
      Ranolazine treatment was associated with a reduction in 24-hour burden of
      premature ventricular complexes compared with placebo (>50% reduction versus
      baseline in 61% versus 31%, respectively; P=0.042). However, changes in
      prohormone brain natriuretic peptide levels did not differ in the ranolazine
      compared with the placebo group (geometric mean median [interquartile range], -3
      pg/mL [-107, 142 pg/mL] versus 78 pg/mL [-71, 242 pg/mL]; P=0.251). Furthermore,
      E/E' ratio and quality of life scores showed no significant difference.
      CONCLUSIONS: In patients with nonobstructive HCM, ranolazine showed no overall
      effect on exercise performance, plasma prohormone brain natriuretic peptide
      levels, diastolic function, or quality of life. The drug showed an excellent
      safety profile and was associated with reduced premature ventricular complex
      burden. Late sodium current inhibition does not seem to improve functional
      capacity in HCM. CLINICAL TRIAL REGISTRATION: URL:
      https://www.clinicaltrialsregister.eu. Unique identifier: 2011-004507-20.

PMID- 29321133
TI  - Evolving Story of Clinical Trials in Hypertrophic Cardiomyopathy.

PMID- 29321134
TI  - Efficacy of a Chronic Care-Based Intervention on Secondary Stroke Prevention
      Among Vulnerable Stroke Survivors: A Randomized Controlled Trial.
AB  - BACKGROUND: Disparities of care among stroke survivors are well documented.
      Effective interventions to improve recurrent stroke preventative care in
      vulnerable populations are lacking. METHODS AND RESULTS: In a randomized
      controlled trial, we tested the efficacy of components of a chronic care model
      based intervention versus usual care among 404 subjects having an ischemic stroke
      or transient ischemic attack within 90 days of enrollment and receiving care
      within the Los Angeles public healthcare system. Subjects had baseline systolic
      blood pressure (SBP) >=120 mm Hg. The intervention included a nurse
      practitioner/physician assistant care manager, group clinics, self-management
      support, report cards, decision support, and ongoing care coordination. Outcomes
      were collected at 3, 8, and 12 months, analyzed as intention-to-treat, and used
      repeated-measures mixed-effects models. Change in SBP was the primary outcome.
      Low-density lipoprotein reduction, antithrombotic medication use, smoking
      cessation, and physical activity were secondary outcomes. Average age was 57
      years; 18% were of black race; 69% were of Hispanic ethnicity. Mean baseline SBP
      was 150 mm Hg in both arms. SBP decreased to 17 mm Hg in the intervention arm and
      14 mm Hg in the usual care arm; the between-arm difference was not significant (
      3.6 mm Hg; 95% confidence interval, -9.2 to 2.2). Among secondary outcomes, the
      only significant difference was that persons in the intervention arm were more
      likely to lower their low-density lipoprotein <100 md/dL (2.0 odds ratio; 95%
      confidence interval, 1.1-3.5). CONCLUSIONS: This intervention did not improve SBP
      control beyond that attained in usual care among vulnerable stroke survivors. A
      community-centered component could strengthen the intervention impact. CLINICAL
      TRIAL REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier:
      NCT00861081.

PMID- 29321136
TI  - Importance and Challenges of Moving Stroke Prevention into the Community.

PMID- 29321135
TI  - Acute Myocardial Infarction Readmission Risk Prediction Models: A Systematic
      Review of Model Performance.
AB  - BACKGROUND: Hospitals are subject to federal financial penalties for excessive 30
      day hospital readmissions for acute myocardial infarction (AMI). Prospectively
      identifying patients hospitalized with AMI at high risk for readmission could
      help prevent 30-day readmissions by enabling targeted interventions. However, the
      performance of AMI-specific readmission risk prediction models is unknown.
      METHODS AND RESULTS: We systematically searched the published literature through
      March 2017 for studies of risk prediction models for 30-day hospital readmission
      among adults with AMI. We identified 11 studies of 18 unique risk prediction
      models across diverse settings primarily in the United States, of which 16 models
      were specific to AMI. The median overall observed all-cause 30-day readmission
      rate across studies was 16.3% (range, 10.6%-21.0%). Six models were based on
      administrative data; 4 on electronic health record data; 3 on clinical hospital
      data; and 5 on cardiac registry data. Models included 7 to 37 predictors, of
      which demographics, comorbidities, and utilization metrics were the most
      frequently included domains. Most models, including the Centers for Medicare and
      Medicaid Services AMI administrative model, had modest discrimination (median C
      statistic, 0.65; range, 0.53-0.79). Of the 16 reported AMI-specific models, only
      8 models were assessed in a validation cohort, limiting generalizability.
      Observed risk-stratified readmission rates ranged from 3.0% among the lowest-risk
      individuals to 43.0% among the highest-risk individuals, suggesting good risk
      stratification across all models. CONCLUSIONS: Current AMI-specific readmission
      risk prediction models have modest predictive ability and uncertain
      generalizability given methodological limitations. No existing models provide
      actionable information in real time to enable early identification and risk
      stratification of patients with AMI before hospital discharge, a functionality
      needed to optimize the potential effectiveness of readmission reduction
      interventions.

PMID- 29321138
TI  - Sensorimotor Functional and Structural Networks after Intracerebral Stem Cell
      Grafts in the Ischemic Mouse Brain.
AB  - Past investigations on stem cell-mediated recovery after stroke have limited
      their focus on the extent and morphological development of the ischemic lesion
      itself over time or on the integration capacity of the stem cell graft ex vivo
      However, an assessment of the long-term functional and structural improvement in
      vivo is essential to reliably quantify the regenerative capacity of cell
      implantation after stroke. We induced ischemic stroke in nude mice and implanted
      human neural stem cells (H9 derived) into the ipsilateral cortex in the acute
      phase. Functional and structural connectivity changes of the sensorimotor network
      were noninvasively monitored using magnetic resonance imaging for 3 months after
      stem cell implantation. A sharp decrease of the functional sensorimotor network
      extended even to the contralateral hemisphere, persisting for the whole 12 weeks
      of observation. In mice with stem cell implantation, functional networks were
      stabilized early on, pointing to a paracrine effect as an early supportive
      mechanism of the graft. This stabilization required the persistent vitality of
      the stem cells, monitored by bioluminescence imaging. Thus, we also observed
      deterioration of the early network stabilization upon vitality loss of the graft
      after a few weeks. Structural connectivity analysis showed fiber-density
      increases between the cortex and white matter regions occurring predominantly on
      the ischemic hemisphere. These fiber-density changes were nearly the same for
      both study groups. This motivated us to hypothesize that the stem cells can
      influence, via early paracrine effect, the functional networks, while observed
      structural changes are mainly stimulated by the ischemic event.SIGNIFICANCE
      STATEMENT In recent years, research on strokes has made a shift away from a focus
      on immediate ischemic effects and towards an emphasis on the long-range effects
      of the lesion on the whole brain. Outcome improvements in stem cell therapies
      also require the understanding of their influence on the whole-brain networks.
      Here, we have longitudinally and noninvasively monitored the structural and
      functional network alterations in the mouse model of focal cerebral ischemia.
      Structural changes of fiber-density increases are stimulated in the endogenous
      tissue without further modulation by the stem cells, while functional networks
      are stabilized by the stem cells via a paracrine effect. These results will help
      decipher the underlying networks of brain plasticity in response to cerebral
      lesions and offer clues to unravelling the mystery of how stem cells mediate
      regeneration.

PMID- 29321137
TI  - Novel function of ceramide for regulation of mitochondrial ATP release in
      astrocytes.
AB  - We reported that amyloid beta peptide (Abeta42) activated neutral SMase 2
      (nSMase2), thereby increasing the concentration of the sphingolipid ceramide in
      astrocytes. Here, we show that Abeta42 induced mitochondrial fragmentation in
      wild-type astrocytes, but not in nSMase2-deficient cells or astrocytes treated
      with fumonisin B1 (FB1), an inhibitor of ceramide synthases. Unexpectedly,
      ceramide depletion was concurrent with rapid movements of mitochondria,
      indicating an unknown function of ceramide for mitochondria. Using
      immunocytochemistry and super-resolution microscopy, we detected ceramide
      enriched and mitochondria-associated membranes (CEMAMs) that were codistributed
      with microtubules. Interaction of ceramide with tubulin was confirmed by cross
      linking to N-[9-(3-pent-4-ynyl-3-H-diazirine-3-yl)-nonanoyl]-D-erythro
      sphingosine (pacFACer), a bifunctional ceramide analog, and binding of tubulin to
      ceramide-linked agarose beads. Ceramide-associated tubulin (CAT) translocated
      from the perinuclear region to peripheral CEMAMs and mitochondria, which was
      prevented in nSMase2-deficient or FB1-treated astrocytes. Proximity ligation and
      coimmunoprecipitation assays showed that ceramide depletion reduced association
      of tubulin with voltage-dependent anion channel 1 (VDAC1), an interaction known
      to block mitochondrial ADP/ATP transport. Ceramide-depleted astrocytes contained
      higher levels of ATP, suggesting that ceramide-induced CAT formation leads to
      VDAC1 closure, thereby reducing mitochondrial ATP release, and potentially
      motility and resistance to Abeta42 Our data also indicate that inhibiting
      ceramide generation may protect mitochondria in Alzheimer's disease.

PMID- 29321140
TI  - Cerebrospinal fluid Alzheimer biomarkers can be useful for discriminating
      dementia with Lewy bodies from Alzheimer's disease at the prodromal stage.
AB  - BACKGROUND: Differential diagnosis between dementia with Lewy bodies (DLB) and
      Alzheimer's disease (AD) is not straightforward, especially in the early stages
      of disease. We compared AD biomarkers (phospho-Tau181, total-Tau, Abeta42 and
      Abeta40) in cerebrospinal fluid (CSF) of patients with DLB and AD, focusing
      especially on the prodromal stage. METHODS: A total of 1221 CSF were collected in
      different memory centres (ePLM network) in France and analysed retrospectively.
      Samples were obtained from patients with prodromal DLB (pro-DLB; n=57), DLB
      dementia (DLB-d; n=154), prodromal AD (pro-AD; n=132) and AD dementia (n=783),
      and control subjects (CS; n=95). These centres use the same diagnostic procedure
      and criteria to evaluate the patients. RESULTS: In patients with pro-DLB, CSF
      Abeta42 levels appeared much less disrupted than in patients at the demented
      stage (DLB-d) (P<0.05 CS>pro-DLB; P<0.001 CS>DLB-d). On average, Abeta40 levels
      in patients with DLB (pro-DLB and DLB-d) were much below those in patients with
      pro-AD (P<0.001 DLB groups<pro-AD). The Abeta42/Abeta40 ratio in patients with
      pro-DLB remained close to that of CS. t-Tau and phospho-Tau181 levels were
      unaltered in patients with DLB (pro-DLB and DLB-d). CONCLUSIONS: Reduced levels
      of CSF Abeta42 were found in patients with DLB but rather at a later stage,
      reaching those of patients with AD, in whom Abeta42 levels were decreased even at
      the prodromal stage. At the prodromal stage of DLB, the majority of patients
      presented a normal CSF profile. CSF t-Tau and phospho-Tau181 were the best
      biomarkers to discriminate between AD and DLB, whatever the stage of disease.

PMID- 29321139
TI  - BMP/SMAD Pathway Promotes Neurogenesis of Midbrain Dopaminergic Neurons In Vivo
      and in Human Induced Pluripotent and Neural Stem Cells.
AB  - The embryonic formation of midbrain dopaminergic (mDA) neurons in vivo provides
      critical guidelines for the in vitro differentiation of mDA neurons from stem
      cells, which are currently being developed for Parkinson's disease cell
      replacement therapy. Bone morphogenetic protein (BMP)/SMAD inhibition is
      routinely used during early steps of stem cell differentiation protocols,
      including for the generation of mDA neurons. However, the function of the
      BMP/SMAD pathway for in vivo specification of mammalian mDA neurons is virtually
      unknown. Here, we report that BMP5/7-deficient mice (Bmp5-/-; Bmp7-/-) lack mDA
      neurons due to reduced neurogenesis in the mDA progenitor domain. As molecular
      mechanisms accounting for these alterations in Bmp5-/-; Bmp7-/- mutants, we have
      identified expression changes of the BMP/SMAD target genes MSX1/2 (msh homeobox
      1/2) and SHH (sonic hedgehog). Conditionally inactivating SMAD1 in neural stem
      cells of mice in vivo (Smad1Nes) hampered the differentiation of progenitor cells
      into mDA neurons by preventing cell cycle exit, especially of TH+SOX6+ (tyrosine
      hydroxylase, SRY-box 6) and TH+GIRK2+ (potassium voltage-gated channel subfamily
      J member-6) substantia nigra neurons. BMP5/7 robustly increased the in vitro
      differentiation of human induced pluripotent stem cells and induced neural stem
      cells to mDA neurons by up to threefold. In conclusion, we have identified
      BMP/SMAD signaling as a novel critical pathway orchestrating essential steps of
      mammalian mDA neurogenesis in vivo that balances progenitor proliferation and
      differentiation. Moreover, we demonstrate the potential of BMPs to improve the
      generation of stem-cell-derived mDA neurons in vitro, highlighting the importance
      of sequential BMP/SMAD inhibition and activation in this process.SIGNIFICANCE
      STATEMENT We identify bone morphogenetic protein (BMP)/SMAD signaling as a novel
      essential pathway regulating the development of mammalian midbrain dopaminergic
      (mDA) neurons in vivo and provide insights into the molecular mechanisms of this
      process. BMP5/7 regulate MSX1/2 (msh homeobox 1/2) and SHH (sonic hedgehog)
      expression to direct mDA neurogenesis. Moreover, the BMP signaling component
      SMAD1 controls the differentiation of mDA progenitors, particularly to substantia
      nigra neurons, by directing their cell cycle exit. Importantly, BMP5/7 increase
      robustly the differentiation of human induced pluripotent and induced neural stem
      cells to mDA neurons. BMP/SMAD are routinely inhibited in initial stages of stem
      cell differentiation protocols currently being developed for Parkinson's disease
      cell replacement therapies. Therefore, our findings on opposing roles of the
      BMP/SMAD pathway during in vitro mDA neurogenesis might improve these procedures
      significantly.

PMID- 29321142
TI  - Differentiating Primary, Genetic, and Secondary FSGS in Adults: A
      Clinicopathologic Approach.
AB  - FSGS describes a renal histologic lesion with diverse causes and pathogenicities
      that are linked by podocyte injury and depletion. Subclasses of FSGS include
      primary, genetic, and secondary forms, the latter comprising maladaptive, viral,
      and drug-induced FSGS. Despite sharing certain clinical and histologic features,
      these subclasses differ noticeably in management and prognosis. Without an
      accepted nongenetic biomarker that discriminates among these FSGS types,
      classification of patients is often challenging. This review summarizes the
      clinical and histologic features, including the onset and severity of proteinuria
      as well as the presence of nephrotic syndrome, that may aid in identifying the
      specific FSGS subtype. The FSGS lesion is characterized by segmental sclerosis
      and must be differentiated from nonspecific focal global glomerulosclerosis. No
      light microscopic features are pathognomonic for a particular FSGS subcategory.
      The characteristics of podocyte foot process effacement on electron microscopy,
      while helpful in discriminating between primary and maladaptive FSGS, may be of
      little utility in detecting genetic forms of FSGS. When FSGS cannot be classified
      by clinicopathologic assessment, genetic analysis should be offered. Next
      generation DNA sequencing enables cost-effective screening of multiple genes
      simultaneously, but determining the pathogenicity of a detected genetic variant
      may be challenging. A more systematic evaluation of patients, as suggested
      herein, will likely improve therapeutic outcomes and the design of future trials
      in FSGS.

PMID- 29321141
TI  - Efficacy of intensive multidisciplinary rehabilitation in Parkinson's disease: a
      randomised controlled study.
AB  - OBJECTIVE: To evaluate whether a 4-week multidisciplinary, aerobic, motor
      cognitive and intensive rehabilitation treatment (MIRT) improves the quality of
      life (QoL) of patients with Parkinson's disease (PD), in the short-term and long
      term period. METHODS: This is a prospective, parallel-group, single-centre,
      single-blind, randomised clinical trial (ClinicalTrials.gov NCT02756676). 186
      patients with PD, assigned to experimental group, underwent MIRT; conversely, 48
      patients, assigned to control group, did not receive rehabilitation. Parkinson's
      Disease Questionnaire-39 was assessed 2 (T0), 10 (T1) and 18 (T2, only
      experimental group) weeks after the enrolment. We compared T1 versus T0 scores
      within subjects and delta scores (T1-T0) between subjects. To investigate the
      long-term effects, we compared T2 and T0 scores in the experimental group.
      RESULTS: At T0, no between-group differences in the Global Index Score (GBI) were
      observed (experimental group: 43.6+/-21.4, controls: 41.6+/-22.9, P=0.50). At T1,
      we did not find significant changes in controls (delta score: 1.2+/-9.9, P=0.23),
      and we found an improvement in GBI in the experimental group (delta score: -8.3+/
      18.0, P<0.0001), significant also between subjects (P<0.0001). Comparing T2
      versus T0 in the experimental group, the GBI maintained a significant improvement
      (delta score: -4.8+/-17.5, P<0.0001). CONCLUSIONS: A rehabilitation treatment
      such as MIRT could improve QoL in patients with PD in the short-term and long
      term period. Even though the single-blind design and the possible role of the
      placebo effect on the conclusive results must be considered as limitations of
      this study, the improvement in outcome measure, also maintained after a 3-month
      follow-up period, suggests the effectiveness of MIRT on the QoL. CLINICAL TRIAL
      REGISTRATION: NCT02756676: Pre-results.

PMID- 29321143
TI  - Control of Humoral Response in Renal Transplantation by Belatacept Depends on a
      Direct Effect on B Cells and Impaired T Follicular Helper-B Cell Crosstalk.
AB  - Generation of de novo donor-specific antibodies (dnDSAs) after renal transplant
      is recognized as the leading cause of late transplant failure. Hence, the optimal
      immunosuppressive strategies to limit dnDSA development need to be defined.
      Recent clinical trials using the novel costimulatory blockade agent CTLA4-Ig
      (Belatacept) have shown that kidney transplant recipients (KTRs) treated with
      Belatacept have better graft survival and function and a lower proportion of
      dnDSAs than control-treated KTRs. Mechanisms involved in the control of humoral
      responses by Belatacept remain to be investigated. Here, we analyzed the effect
      of Belatacept on different steps of the B cell-mediated response in humans. In
      vitro, Belatacept reduced plasmablast differentiation, Ig production, and the
      expression of the major transcription factor involved in plasma cell function,
      Blimp-1, in a T cell-independent manner. Moreover, Belatacept induced activation
      of the STAT3 transcription factor in stimulated B cells and reduced the
      expression of CD86. Additionally, Belatacept blocked CD28-mediated activation of
      T follicular helper cells (Tfhs) in an autologous Tfh-memory B cells model. We
      then validated these observations in KTRs treated with Belatacept, who had a
      reduced proportion of blood effector B cells and activated Tfh (PD1+ICOS+)
      compared with control-treated KTRs. Our in vitro and in vivo results suggest that
      Belatacept modulates B cell function directly and at the level of B cell-Tfh
      interaction. These mechanisms likely account for the optimal control of humoral
      responses observed in KTRs treated with Belatacept.

PMID- 29321144
TI  - Cognitive Control, the Anterior Cingulate, and Nicotinic Receptors: A Case of
      Heterozygote Advantage.

PMID- 29321145
TI  - Does Auditory Cortex Code Temporal Information from Acoustic and Cochlear Implant
      Stimulation in a Similar Way?

PMID- 29321146
TI  - Authors' reply to Madhavan.

PMID- 29321147
TI  - Psychotic symptoms in people with intellectual disability.

PMID- 29321148
TI  - Many smokers overestimate e-cigarette risks, MPs hear.

PMID- 29321149
TI  - Improving the conduct, reporting, and appraisal of animal research.

PMID- 29321150
TI  - Communitisation of healthcare: peer support groups for chronic disease care in
      rural India.

PMID- 29321151
TI  - Diet, genes, and obesity.

PMID- 29321152
TI  - CQC suspends inspections in response to winter pressures.

PMID- 29321153
TI  - Margaret McCartney: When a crisis is the predictable outcome of poor policy
      making.

PMID- 29321154
TI  - Learning lessons from MVA85A, a failed booster vaccine for BCG.

PMID- 29321155
TI  - Plasminogen replacement therapy for the treatment of children and adults with
      congenital plasminogen deficiency.
AB  - Congenital plasminogen deficiency is caused by mutations in PLG, the gene coding
      for production of the zymogen plasminogen, and is an ultrarare disorder
      associated with abnormal accumulation or growth of fibrin-rich pseudomembranous
      lesions on mucous membranes. Left untreated, these lesions may impair organ
      function and impact quality of life. Plasminogen replacement therapy should
      provide an effective treatment of the manifestations of congenital plasminogen
      deficiency. An open-label phase 2/3 study of human Glu-plasminogen administered
      IV at 6.6 mg/kg every 2 to 4 days in 15 patients with congenital plasminogen
      deficiency is ongoing. Reported here are data on 14 patients who completed at
      least 12 weeks of treatment. The primary end point was an increase in trough
      plasminogen activity levels by at least an absolute 10% above baseline. The
      secondary end point was clinical success, defined as >=50% improvement in lesion
      number/size or functionality impact from baseline. All patients achieved at least
      an absolute 10% increase in trough plasminogen activity above baseline. Clinical
      success was observed in all patients with clinically visible (conjunctiva and
      gingiva), nonvisible (nasopharynx, bronchus, colon, kidney, cervix, and vagina),
      and wound-healing manifestations of the disease. Therapeutic effects were rapid,
      as all but 2 lesions resolved or improved after 4 weeks of treatment. Human Glu
      plasminogen was well tolerated in both children and adults. This study provides
      critical first evidence of the clinical utility of ongoing replacement therapy
      with human Glu-plasminogen for the treatment of children and adults with
      congenital plasminogen deficiency. This trial was registered at
      www.clinicaltrials.gov as #NCT02690714.

PMID- 29321156
TI  - Improving adherence to healthy dietary patterns, genetic risk, and long term
      weight gain: gene-diet interaction analysis in two prospective cohort studies.
AB  - OBJECTIVE: To investigate whether improving adherence to healthy dietary patterns
      interacts with the genetic predisposition to obesity in relation to long term
      changes in body mass index and body weight. DESIGN: Prospective cohort study.
      SETTING: Health professionals in the United States. PARTICIPANTS: 8828 women from
      the Nurses' Health Study and 5218 men from the Health Professionals Follow-up
      Study. EXPOSURE: Genetic predisposition score was calculated on the basis of 77
      variants associated with body mass index. Dietary patterns were assessed by the
      Alternate Healthy Eating Index 2010 (AHEI-2010), Dietary Approach to Stop
      Hypertension (DASH), and Alternate Mediterranean Diet (AMED). MAIN OUTCOME
      MEASURES: Five repeated measurements of four year changes in body mass index and
      body weight over follow-up (1986 to 2006). RESULTS: During a 20 year follow-up,
      genetic association with change in body mass index was significantly attenuated
      with increasing adherence to the AHEI-2010 in the Nurses' Health Study (P=0.001
      for interaction) and Health Professionals Follow-up Study (P=0.005 for
      interaction). In the combined cohorts, four year changes in body mass index per
      10 risk allele increment were 0.07 (SE 0.02) among participants with decreased
      AHEI-2010 score and -0.01 (0.02) among those with increased AHEI-2010 score,
      corresponding to 0.16 (0.05) kg versus -0.02 (0.05) kg weight change every four
      years (P<0.001 for interaction). Viewed differently, changes in body mass index
      per 1 SD increment of AHEI-2010 score were -0.12 (0.01), -0.14 (0.01), and -0.18
      (0.01) (weight change: -0.35 (0.03), -0.36 (0.04), and -0.50 (0.04) kg) among
      participants with low, intermediate, and high genetic risk, respectively. Similar
      interaction was also found for DASH but not for AMED. CONCLUSIONS: These data
      indicate that improving adherence to healthy dietary patterns could attenuate the
      genetic association with weight gain. Moreover, the beneficial effect of improved
      diet quality on weight management was particularly pronounced in people at high
      genetic risk for obesity.

PMID- 29321158
TI  - Response to: 'Calprotectin is not independent from baseline erosion in predicting
      radiological progression in early rheumatoid arthritis' by Chevreau et al.

PMID- 29321157
TI  - Calprotectin is not independent from baseline erosion in predicting radiological
      progression in early rheumatoid arthritis. Comment on 'Calprotectin as a marker
      of inflammation in patients with early rheumatoid arthritis' by Jonsson et al.

PMID- 29321160
TI  - Avoid stigmatising language for people who use drugs, global commission urges.

PMID- 29321159
TI  - Impact of specialist palliative care on coping with Parkinson's disease: patients
      and carers.
AB  - OBJECTIVES: UK guidelines recommend palliative care access for people with
      Parkinson's disease; however, this remains sporadic, and it is unknown whether
      specialist palliative care helps patients and carers cope with this distressing
      condition. This study aimed to explore whether, and how, access to specialist
      palliative care services affected patients' and carers' coping with Parkinson's
      disease. METHODS: Semistructured interviews were conducted, audio-recorded and
      verbatim transcribed. Data were analysed using interpretative phenomenological
      analysis. Participants were patients with advanced idiopathic Parkinson's disease
      (n=3), and carers of people with Parkinson's disease (n=5, however, one diagnosis
      was reviewed) receiving care from an integrated specialist palliative care and
      Parkinson's disease service in North East England. RESULTS: Access to specialist
      palliative care helped participants cope with some aspects of advanced
      Parkinson's disease. Three superordinate themes were developed:' managing
      uncertainty', 'impacts on the self' and 'specialist palliative care maintaining a
      positive outlook'. CONCLUSIONS: Specialist palliative care helped patients and
      carers cope with advanced Parkinson's disease. Specialist palliative care is a
      complex intervention that acknowledges the complex and holistic nature of
      Parkinson's disease, enabling health in some domains despite continued presence
      of pathology. These exploratory findings support the utility of this approach for
      people living with Parkinson's disease.

PMID- 29321161
TI  - Simon Denegri: Piloting patient involvement.

PMID- 29321162
TI  - Risk of Suicide Attempt in Poststroke Patients: A Population-Based Cohort Study.
AB  - BACKGROUND: This nationwide population-based cohort study evaluated the risk of
      and risk factors for suicide attempt in poststroke patients in Taiwan. METHODS
      AND RESULTS: The poststroke and nonstroke cohorts consisted of 713 690 patients
      and 1 426 009 controls, respectively. Adults (aged >18 years) who received new
      stroke diagnoses according to the International Classification of Diseases, Ninth
      Revision, Clinical Modification (ICD-9-CM; codes 430-438) between 2000 and 2011
      were included in the poststroke cohort. We calculated the adjusted hazard ratio
      for suicide attempt (ICD-9-CM codes E950-E959) after adjustment for age, sex,
      monthly income, urbanization level, occupation category, and various
      comorbidities. Kaplan-Meier analysis was used to measure the cumulative incidence
      of suicide attempt, and the Fine and Gray method was used as a competing event
      when estimating death subhazard ratios and 95% confidence intervals between
      groups. The cumulative incidence of suicide attempt was higher in the poststroke
      cohort, and the adjusted hazard ratio of suicide attempt was 2.20 (95% confidence
      interval, 2.04-2.37) compared with that of the controls. The leading risk factors
      for poststroke suicide attempt were earning low monthly income (<660 US dollars),
      living in less urbanized regions, doing manual labor, and having a stroke before
      age 50 years. The attempted suicide risk did not differ significantly between
      male and female patients in this study. CONCLUSIONS: These results convey crucial
      information to clinicians and governments for preventing suicide attempt in
      poststroke patients in Taiwan and other Asian countries.

PMID- 29321163
TI  - Antitumor Effects of Blocking Protein Neddylation in T315I-BCR-ABL Leukemia Cells
      and Leukemia Stem Cells.
AB  - Imatinib revolutionized the treatment of chronic myeloid leukemia (CML), but drug
      resistance and disease recurrence remain a challenge. In this study, we suggest a
      novel strategy based on blocking protein neddylation to address BCR-ABL point
      mutations and leukemia stem cells (LSC) that lie at the root of imatinib
      resistant recurrences. On the basis of the finding that the NEDD8-activating
      enzyme subunit NAE1 is overexpressed in CML cells, we hypothesized that the
      function of certain neddylation-dependent protein substrates might be targeted to
      therapeutic ends in imatinib-resistant CML cells and LSCs. In support of this
      hypothesis, we demonstrated that the NAE1 inhibitor MLN4924 induced G2-M-phase
      arrest and apoptosis in bulk CML cells with wild-type p53, regardless of their
      T315I mutation status in BCR-ABL. Moreover, MLN4924 inhibited the survival and
      self-renewal of primary human CML CD34+ cells and LSCs in CML-bearing mice via
      accumulation of p27kip1 in the nucleus. Notably, p27kip1 silencing attenuated the
      suppressive effect of MLN4924 on the maintenance of LSCs in CML-bearing mice.
      Taken together, our findings offer a preclinical proof of concept for targeting
      protein neddylation as a novel therapeutic strategy to override mutational and
      LSC-derived imatinib resistance in CML.Significance: These findings highlight a
      mediator of protein neddylation, a type of protein turnover mechanism, as a
      viable therapeutic target against imatinib-resistant forms of chronic myelogenous
      leukemia. Cancer Res; 78(6); 1522-36. (c)2018 AACR.

PMID- 29321165
TI  - Oxford vaccine study highlights pick and mix approach to preclinical research.

PMID- 29321164
TI  - KRAS Oncoprotein Expression Is Regulated by a Self-Governing eIF5A-PEAK1 Feed
      Forward Regulatory Loop.
AB  - There remains intense interest in tractable approaches to target or silence the
      KRAS oncoprotein as a rational therapeutic strategy to attack pancreatic ductal
      adenocarcinoma (PDAC) and other cancers that overexpress it. Here we provide
      evidence that accumulation of the KRAS oncoprotein is controlled by a self
      regulating feed-forward regulatory loop that utilizes a unique hypusinated
      isoform of the translation elongation factor eIF5A and the tyrosine kinase PEAK1.
      Oncogenic activation of KRAS increased eIF5A-PEAK1 translational signaling, which
      in turn facilitated increased KRAS protein synthesis. Mechanistic investigations
      show that this feed-forward positive regulatory pathway was controlled by
      oncogenic KRAS-driven metabolic demands, operated independently of canonical mTOR
      signaling, and did not involve new KRAS gene transcription. Perturbing eIF5A
      PEAK1 signaling, by genetic or pharmacologic strategies or by blocking glutamine
      synthesis, was sufficient to inhibit expression of KRAS, eIF5A, and PEAK1, to
      attenuate cancer cell growth and migration, and to block tumor formation in
      established preclinical mouse models of PDAC. Levels of KRAS, eIF5A, and PEAK1
      protein increased during cancer progression with the highest levels of expression
      observed in metastatic cell populations. Combinatorial targeting of eIF5A
      hypusination and the RAS-ERK signaling pathway cooperated to attenuate KRAS
      expression and its downstream signaling along with cell growth in vitro and tumor
      formation in vivo Collectively, our findings highlight a new mechanistic strategy
      to attenuate KRAS expression as a therapeutic strategy to target PDAC and other
      human cancers driven by KRAS activation.Significance: These findings highlight a
      new mechanistic strategy to attenuate KRAS expression as a therapeutic strategy
      to target human cancers driven by KRAS activation. Cancer Res; 78(6); 1444-56.
      (c)2018 AACR.

PMID- 29321166
TI  - Fetal and early life antibiotics exposure and very early onset inflammatory bowel
      disease: a population-based study.
AB  - OBJECTIVE: Earlier studies on antibiotics exposure and development of IBD
      (Crohn's disease (CD) and ulcerative colitis (UC)) may have been biased by
      familial factors and gastroenteritis. We aimed to estimate the association
      between antibiotics during pregnancy or infantile age and very early onset (VEO)
      IBD. DESIGN: In this cohort study of 827 239 children born in Sweden between 2006
      and 2013, we examined the link between exposure to systemic antibiotics and VEO
      IBD (diagnosis <6 years of age), using Cox proportional hazard regression models.
      Information on antibiotics and IBD was retrieved from the nationwide population
      based Swedish Prescribed Drug Register and the National Patient Register. We
      specifically examined potential confounding from parental IBD and
      gastroenteritis. RESULTS: Children exposed to antibiotics during pregnancy were
      at increased risk of IBD compared with general population controls (adjusted HR
      (aHR) 1.93; 95% CI 1.06 to 3.50). Corresponding aHRs were 2.48 (95% CI 1.01 to
      6.08) for CD and 1.25 (95% CI 0.47 to 3.26) for UC, respectively. For antibiotics
      in infantile age, the aHR for IBD was 1.11 (95% CI 0.57 to 2.15); for CD 0.72
      (95% CI 0.27 to 1.92) and 1.23 (95% CI 0.45 to 3.39) for UC. Excluding children
      with gastroenteritis 12 months prior to the first IBD diagnosis retained similar
      aHR for antibiotics during pregnancy and CD, while the association no longer
      remained significant for IBD. CONCLUSION: We found that exposure to antibiotics
      during pregnancy, but not in infantile age, is associated with an increased risk
      of VEO-IBD regardless of gastroenteritis. The risk increase for exposure in
      pregnancy may be due to changes in the microbiota.

PMID- 29321167
TI  - Construction of Designer Selectable Marker Deletions with a CRISPR-Cas9 Toolbox
      in Schizosaccharomyces pombe and New Design of Common Entry Vectors.
AB  - Vectors encoding selectable markers have been widely used in yeast to maintain or
      express exogenous DNA fragments. In the fission yeast Schizosaccharomyces pombe,
      several engineered markers have been reported and widely used, such as ura4+ and
      ScLEU2 from Saccharomyces cerevisiae, which complement ura4 and leu1 mutations,
      respectively. These two auxotrophic markers share no homology with the S. pombe
      genome; however, most others can recombine with the genome due to sequence
      homology shared between the genomic and plasmid-borne copies of the markers.
      Here, we describe a CRISPR-Cas9 toolbox that can be used to quickly introduce
      "designer" auxotrophic marker deletions into host strains, including leu1-Delta0,
      his3-Delta0, and lys9-Delta0 Together with ura4-D18, this brings the total number
      of available designer deletion auxotrophic markers to four. The toolbox consists
      of a Cas9-gRNA expression vector and a donor DNA plasmid pair for each designer
      deletion. Using this toolbox, a set of auxotrophic S. pombe strains was
      constructed. Further, we reorganized essential components in the commonly used
      pREP series of plasmids and assembled the corresponding auxotrophic marker gene
      onto these plasmids. This toolbox for producing designer deletions, together with
      the newly developed strains and plasmids, will benefit the whole yeast community.

PMID- 29321168
TI  - Tools Allowing Independent Visualization and Genetic Manipulation of Drosophila
      melanogaster Macrophages and Surrounding Tissues.
AB  - Drosophila melanogaster plasmatocytes, the phagocytic cells among hemocytes, are
      essential for immune responses, but also play key roles from early development to
      death through their interactions with other cell types. They regulate homeostasis
      and signaling during development, stem cell proliferation, metabolism, cancer,
      wound responses, and aging, displaying intriguing molecular and functional
      conservation with vertebrate macrophages. Given the relative ease of genetics in
      Drosophila compared to vertebrates, tools permitting visualization and genetic
      manipulation of plasmatocytes and surrounding tissues independently at all stages
      would greatly aid a fuller understanding of these processes, but are lacking.
      Here, we describe a comprehensive set of transgenic lines that allow this. These
      include extremely brightly fluorescing mCherry-based lines that allow GAL4
      independent visualization of plasmatocyte nuclei, the cytoplasm, or the actin
      cytoskeleton from embryonic stage 8 through adulthood in both live and fixed
      samples even as heterozygotes, greatly facilitating screening. These lines allow
      live visualization and tracking of embryonic plasmatocytes, as well as larval
      plasmatocytes residing at the body wall or flowing with the surrounding
      hemolymph. With confocal imaging, interactions of plasmatocytes and inner tissues
      can be seen in live or fixed embryos, larvae, and adults. They permit efficient
      GAL4-independent Fluorescence-Activated Cell Sorting (FACS) analysis/sorting of
      plasmatocytes throughout life. To facilitate genetic studies of reciprocal
      signaling, we have also made a plasmatocyte-expressing QF2 line that, in
      combination with extant GAL4 drivers, allows independent genetic manipulation of
      both plasmatocytes and surrounding tissues, and GAL80 lines that block GAL4
      drivers from affecting plasmatocytes, all of which function from the early embryo
      to the adult.

PMID- 29321169
TI  - The actin-MRTF-SRF transcriptional circuit controls tubulin acetylation via alpha
      TAT1 gene expression.
AB  - The role of formins in microtubules is not well understood. In this study, we
      have investigated the mechanism by which INF2, a formin mutated in degenerative
      renal and neurological hereditary disorders, controls microtubule acetylation. We
      found that silencing of INF2 in epithelial RPE-1 cells produced a dramatic drop
      in tubulin acetylation, increased the G-actin/F-actin ratio, and impaired
      myocardin-related transcription factor (MRTF)/serum response factor (SRF)
      dependent transcription, which is known to be repressed by increased levels of G
      actin. The effect on tubulin acetylation was caused by the almost complete
      absence of alpha-tubulin acetyltransferase 1 (alpha-TAT1) messenger RNA (mRNA).
      Activation of the MRTF-SRF transcriptional complex restored alpha-TAT1 mRNA
      levels and tubulin acetylation. Several functional MRTF-SRF-responsive elements
      were consistently identified in the alpha-TAT1 gene. The effect of INF2 silencing
      on microtubule acetylation was also observed in epithelial ECV304 cells, but not
      in Jurkat T cells. Therefore, the actin-MRTF-SRF circuit controls alpha-TAT1
      transcription. INF2 regulates the circuit, and hence microtubule acetylation, in
      cell types where it has a prominent role in actin polymerization.

PMID- 29321170
TI  - An interaction between myosin-10 and the cell cycle regulator Wee1 links spindle
      dynamics to mitotic progression in epithelia.
AB  - Anaphase in epithelia typically does not ensue until after spindles have achieved
      a characteristic position and orientation, but how or even if cells link spindle
      position to anaphase onset is unknown. Here, we show that myosin-10 (Myo10), a
      motor protein involved in epithelial spindle dynamics, binds to Wee1, a conserved
      regulator of cyclin-dependent kinase 1 (Cdk1). Wee1 inhibition accelerates
      progression through metaphase and disrupts normal spindle dynamics, whereas
      perturbing Myo10 function delays anaphase onset in a Wee1-dependent manner.
      Moreover, Myo10 perturbation increases Wee1-mediated inhibitory phosphorylation
      on Cdk1, which, unexpectedly, concentrates at cell-cell junctions. Based on these
      and other results, we propose a model in which the Myo10-Wee1 interaction
      coordinates attainment of spindle position and orientation with anaphase onset.

PMID- 29321171
TI  - SGK1/FOXO3 Signaling in Hypothalamic POMC Neurons Mediates Glucocorticoid
      Increased Adiposity.
AB  - Although the central nervous system has been implicated in glucocorticoid-induced
      gain of fat mass, the underlying mechanisms are poorly understood. The aim of
      this study was to investigate the possible involvement of hypothalamic serum- and
      glucocorticoid-regulated kinase 1 (SGK1) in glucocorticoid-increased adiposity.
      It is well known that SGK1 expression is induced by acute glucocorticoid
      treatment, but it is interesting that we found its expression to be decreased in
      the arcuate nucleus of the hypothalamus, including proopiomelanocortin (POMC)
      neurons, following chronic dexamethasone (Dex) treatment. To study the role of
      SGK1 in POMC neurons, we produced mice that developed or experienced adult-onset
      SGK1 deletion in POMC neurons (PSKO). As observed in Dex-treated mice, PSKO mice
      exhibited increased adiposity and decreased energy expenditure. Mice
      overexpressing constitutively active SGK1 in POMC neurons consistently had the
      opposite phenotype and did not experience Dex-increased adiposity. Finally, Dex
      decreased hypothalamic alpha-melanocyte-stimulating hormone (alpha-MSH) content
      and its precursor Pomc expression via SGK1/FOXO3 signaling, and
      intracerebroventricular injection of alpha-MSH or adenovirus-mediated FOXO3
      knockdown in the arcuate nucleus largely reversed the metabolic alterations in
      PSKO mice. These results demonstrate that POMC SGK1/FOXO3 signaling mediates
      glucocorticoid-increased adiposity, providing new insights into the mechanistic
      link between glucocorticoids and fat accumulation and important hints for
      possible treatment targets for obesity.

PMID- 29321174
TI  - Addressing complexity in population health intervention research: the
      context/intervention interface.
AB  - BACKGROUND: Public health interventions are increasingly being recognised as
      complex and context dependent. Related to this is the need for a systemic and
      dynamic conception of interventions that raises the question of delineating the
      scope and contours of interventions in complex systems. This means identifying
      which elements belong to the intervention (and therefore participate in its
      effects and can be transferred), which ones belong to the context and interact
      with the former to influence results (and therefore must be taken into account
      when transferring the intervention) and which contextual elements are irrelevant
      to the intervention. DISCUSSION: This paper, from which derives criteria based on
      a network framework, operationalises how the context and intervention systems
      interact and identify what needs to be replicated as interventions are
      implemented in different contexts. Representing interventions as networks
      (composed of human and non-human entities), we introduce the idea that the
      density of interconnections among the various entities provides a criterion for
      distinguishing core intervention from intervention context without disconnecting
      the two systems. This differentiates endogenous and exogenous intervention
      contexts and the mediators that connect them, which form the fuzzy and constantly
      changing intervention/context interface. CONCLUSION: We propose that a network
      framework representing intervention/context systems constitutes a promising
      approach for deriving empirical criteria to delineate the scope and contour of
      what is replicable in an intervention. This approach should allow better
      identification and description of the entities that have to be transferred to
      ensure the potential effectiveness of an intervention in a specific context.

PMID- 29321172
TI  - Modest Decreases in Endogenous All-trans-Retinoic Acid Produced by a Mouse Rdh10
      Heterozygote Provoke Major Abnormalities in Adipogenesis and Lipid Metabolism.
AB  - Pharmacological dosing of all-trans-retinoic acid (atRA) controls adiposity in
      rodents by inhibiting adipogenesis and inducing fatty acid oxidation. Retinol
      dehydrogenases (Rdh) catalyze the first reaction that activates retinol into
      atRA. This study examined postnatal contributions of Rdh10 to atRA biosynthesis
      and physiological functions of endogenous atRA. Embryonic fibroblasts from Rdh10
      heterozygote hypomorphs or with a total Rdh10 knockout exhibit decreased atRA
      biosynthesis and escalated adipogenesis. atRA or a retinoic acid receptor (RAR)
      pan-agonist reversed the phenotype. Eliminating one Rdh10 copy in vivo (Rdh10+/-
      ) yielded a modest decrease (<=25%) in the atRA concentration of liver and
      adipose but increased adiposity in male and female mice fed a high-fat diet
      (HFD); increased liver steatosis, glucose intolerance, and insulin resistance in
      males fed an HFD; and activated bone marrow adipocyte formation in females,
      regardless of dietary fat. Chronic dosing with low-dose atRA corrected the
      metabolic defects. These data resolve physiological actions of endogenous atRA,
      reveal sex-specific effects of atRA in vivo, and establish the importance of
      Rdh10 to metabolic control by atRA. The consequences of a modest decrease in
      tissue atRA suggest that impaired retinol activation may contribute to diabesity,
      and low-dose atRA therapy may ameliorate adiposity and its sequelae of glucose
      intolerance and insulin resistance.

PMID- 29321173
TI  - An Autophagy-Independent Role for ATG41 in Sulfur Metabolism During Zinc
      Deficiency.
AB  - The Zap1 transcription factor of Saccharomyces cerevisiae is a key regulator in
      the genomic responses to zinc deficiency. Among the genes regulated by Zap1
      during zinc deficiency is the autophagy-related gene ATG41 Here, we report that
      Atg41 is required for growth in zinc-deficient conditions, but not when zinc is
      abundant or when other metals are limiting. Consistent with a role for Atg41 in
      macroautophagy, we show that nutritional zinc deficiency induces autophagy and
      that mutation of ATG41 diminishes that response. Several experiments indicated
      that the importance of ATG41 function to growth during zinc deficiency is not
      because of its role in macroautophagy, but rather is due to one or more autophagy
      independent functions. For example, rapamycin treatment fully induced autophagy
      in zinc-deficient atg41Delta mutants but failed to improve growth. In addition,
      atg41Delta mutants showed a far more severe growth defect than any of several
      other autophagy mutants tested, and atg41Delta mutants showed increased Heat
      Shock Factor 1 activity, an indicator of protein homeostasis stress, while other
      autophagy mutants did not. An autophagy-independent function for ATG41 in sulfur
      metabolism during zinc deficiency was suggested by analyzing the transcriptome of
      atg41Delta mutants during the transition from zinc-replete to -deficient
      conditions. Analysis of sulfur metabolites confirmed that Atg41 is needed for the
      normal accumulation of methionine, homocysteine, and cysteine in zinc-deficient
      cells. Therefore, we conclude that Atg41 plays roles in both macroautophagy and
      sulfur metabolism during zinc deficiency.

PMID- 29321175
TI  - Upregulation of GH, but not IGF1, in the hippocampus of the lactating dam after
      kainic acid injury.
AB  - Lactation embodies a natural model of morphological, neurochemical, and
      functional brain plasticity. In this reproductive stage, the hippocampus of the
      female is less sensitive to excitotoxins in contrast to nulliparity. Growth
      hormone (GH) and insulin-like growth factor 1 (IGF1) are known to be
      neuroprotective in several experimental models of brain lesion. Here, activation
      of the GH-IGF1 pituitary-brain axis following kainic acid (7.5 mg/kg i.p. KA)
      lesion was studied in lactating and nulliparous rats. Serum concentrations of GH
      and IGF1 were uncoupled in lactation. Compared to virgin rats, the basal
      concentration of GH increased up to 40% but IGF1 decreased 58% in dams, and only
      GH increased further after KA treatment. In the hippocampus, basal expression of
      GH mRNA was higher (2.8-fold) in lactating rats than in virgin rats. GH mRNA
      expression in lactating rats increased further after KA administration in the
      hippocampus and in the hypothalamus, in parallel to GH protein concentration in
      the hippocampus of KA-treated lactating rats (43% vs lactating control), as
      detected by Western blot and immunofluorescence. Except for the significantly
      lower mRNA concentration in the liver of lactating rats, IGF1 expression was not
      altered by the reproductive condition or by KA treatment in the hippocampus and
      hypothalamus. Present results indicate upregulation of GH expression in the
      hippocampus after an excitotoxic lesion, suggesting paracrine/autocrine actions
      of GH as a factor underlying neuroprotection in the brain of the lactating dam.
      Since no induction of IGF1 was detected, present data suggest a direct action of
      GH.

PMID- 29321176
TI  - Effects of Diabetes Medications Targeting the Incretin System on the Kidney.

PMID- 29321177
TI  - Plasticity of the Mre11-Rad50-Xrs2-Sae2 nuclease ensemble in the processing of
      DNA-bound obstacles.
AB  - The budding yeast Mre11-Rad50-Xrs2 (MRX) complex and Sae2 function together in
      DNA end resection during homologous recombination. Here we show that the Ku
      complex shields DNA ends from exonucleolytic digestion but facilitates
      endonucleolytic scission by MRX with a dependence on ATP and Sae2. The incision
      site is enlarged into a DNA gap via the exonuclease activity of MRX, which is
      stimulated by Sae2 without ATP being present. RPA renders a partially resected or
      palindromic DNA structure susceptible to MRX-Sae2, and internal protein blocks
      also trigger DNA cleavage. We present models for how MRX-Sae2 creates entry sites
      for the long-range resection machinery.

PMID- 29321178
TI  - Transcription factor-dependent 'anti-repressive' mammalian enhancers exclude
      H3K27me3 from extended genomic domains.
AB  - Compacted chromatin and nucleosomes are known barriers to gene expression; the
      nature and relative importance of other transcriptional constraints remain
      unclear, especially at distant enhancers. Polycomb repressor complex 2 (PRC2)
      places the histone mark H3K27me3 predominantly at promoters, where its silencing
      activity is well documented. In adult tissues, enhancers lack H3K27me3, and it is
      unknown whether intergenic H3K27me3 deposits affect nearby genes. In primary
      intestinal villus cells, we identified hundreds of tissue-restricted enhancers
      that require the transcription factor (TF) CDX2 to prevent the incursion of
      H3K27me3 from adjoining areas of elevated basal marking into large well
      demarcated genome domains. Similarly, GATA1-dependent enhancers exclude H3K27me3
      from extended regions in erythroid blood cells. Excess intergenic H3K27me3 in
      both TF-deficient tissues is associated with extreme mRNA deficits, which are
      significantly rescued in intestinal cells lacking PRC2. Explaining these
      observations, enhancers show TF-dependent binding of the H3K27 demethylase KDM6A.
      Thus, in diverse cell types, certain genome regions far from promoters accumulate
      H3K27me3, and optimal gene expression depends on enhancers clearing this
      repressive mark. These findings reveal new "anti-repressive" function for
      hundreds of tissue-specific enhancers.

PMID- 29321179
TI  - Physiological protein blocks direct the Mre11-Rad50-Xrs2 and Sae2 nuclease
      complex to initiate DNA end resection.
AB  - DNA double-strand break repair by homologous recombination is initiated by DNA
      end resection, which is commenced by the Mre11-Rad50-Xrs2 complex and Sae2 in
      yeast. Here we report that the nonhomologous end joining factor Ku limits the
      exonuclease activity of Mre11 and promotes its endonuclease to cleave 5'
      terminated DNA strands at break sites. Following initial endonucleolytic cleavage
      past the obstacle, Exo1 specifically extends the resection track, leading to the
      generation of long 3' overhangs that are required for homologous recombination.
      These experiments provide mechanistic insights into how short-range and long
      range DNA end resection enzymes overcome obstacles near broken DNA ends to
      initiate recombination.

PMID- 29321180
TI  - Two-year neurodevelopmental outcomes of extremely preterm infants treated with
      early hydrocortisone: treatment effect according to gestational age at birth.
AB  - OBJECTIVE: To determine whether early hydrocortisone treatment in extremely
      preterm infants affects neurodevelopmental outcomes at 2 years of age according
      to gestational age at birth. PATIENTS AND METHODS: This is an exploratory
      analysis of neurodevelopmental outcomes by gestational age strata from the
      PREMILOC trial, in which patients were randomly assigned to receive either
      placebo or low-dose hydrocortisone and randomisation was stratified by
      gestational age groups (24-25 and 26-27 weeks of gestation). Neurodevelopmental
      impairment (NDI) was assessed using a standardised neurological examination and
      the revised Brunet-Lezine scale at 22 months of corrected age. RESULTS: A total
      of 379 of 406 survivors were evaluated, 96/98 in the gestational age group of 24
      25 weeks and 283/308 in the gestational age group of 26-27 weeks. Among surviving
      infants born at 24-25 weeks, significant improvement in global neurological
      assessment was observed in the hydrocortisone group compared with the placebo
      group (P=0.02) with a risk of moderate-to-severe NDI of 2% and 18%, respectively
      (risk difference 16 (95% CI -28% to -5%)). In contrast, no statistically
      significant difference between treatment groups was observed in infants born at
      26-27 weeks (P=0.95) with a similar risk of moderate-to-severe NDI of 9% in both
      groups. The incidence of cerebral palsy or other major neurological impairments
      were found similar between treatment groups in each gestational group.
      CONCLUSIONS: In an exploratory analysis of neurodevelopmental outcomes from the
      PREMILOC trial, early low-dose hydrocortisone was associated with a statistically
      significant improvement in neurodevelopmental outcomes in infants born at 24 and
      25 weeks of gestation.

PMID- 29321182
TI  - And one last thing.

PMID- 29321183
TI  - PTGS2 polymorphism rs689466 favors breast cancer recurrence in obese patients.
AB  - Breast cancer is the leading cancer among women, and its increasing incidence is
      a challenge worldwide. Estrogen exposure is the main risk factor, but obesity
      among postmenopausal women has been shown to favor disease onset and progression.
      The link between obesity and mammary carcinogenesis involves elevated estrogen
      production and proinflammatory stimuli within the adipose tissue, with activation
      of the cyclooxygenase-2 pathway. Here, we evaluate the impact of the four most
      common cyclooxygenase-2 gene polymorphisms (rs689465, rs689466, rs20417 and
      rs20417), in combination with obesity, on the risk of breast cancer progression
      in a cohort of Brazilian breast cancer patients (N = 1038). Disease-free survival
      was evaluated using Kaplan-Meier curves, with multivariate Cox proportional
      hazards regression models for calculation of adjusted hazard ratios (HRadj).
      Obesity did not affect disease progression, whereas rs689466 variant genotypes
      increased the recurrence risk among obese patients (HRadj = 2.5; 95% CI = 1.4
      4.3), either for luminal (HRadj = 2.2; 95% CI = 1.1-4.2) or HER2-like and triple
      negative tumors (HRadj = 3.2; 95% CI = 1.2-8.5). Likewise, the haplotype *4,
      which contains variant rs689466, was associated with shorter disease-free
      survival among obese patients (HRadj = 3.3; 95% CI = 1.8-6.0), either in luminal
      (HRadj = 3.5; 95% CI = 1.6-7.3) or HER2-like and triple-negative (HRadj = 3.1;
      95% CI = 1.1-8.9) tumors. Such deleterious impact of variant rs689466 on disease
      free survival of obese breast cancer patients was restricted to postmenopausal
      women. In conclusion, cyclooxygenase-2 genotyping may add to the prognostic
      evaluation of obese breast cancer patients.

PMID- 29321185
TI  - Non-genetic diversity modulates population performance.

PMID- 29321184
TI  - A Sizer model for cell differentiation in Arabidopsis thaliana root growth.
AB  - Plant roots grow due to cell division in the meristem and subsequent cell
      elongation and differentiation, a tightly coordinated process that ensures growth
      and adaptation to the changing environment. How the newly formed cells decide to
      stop elongating becoming fully differentiated is not yet understood. To address
      this question, we established a novel approach that combines the quantitative
      phenotypic variability of wild-type Arabidopsis roots with computational data
      from mathematical models. Our analyses reveal that primary root growth is
      consistent with a Sizer mechanism, in which cells sense their length and stop
      elongating when reaching a threshold value. The local expression of
      brassinosteroid receptors only in the meristem is sufficient to set this value.
      Analysis of roots insensitive to BR signaling and of roots with gibberellin
      biosynthesis inhibited suggests distinct roles of these hormones on cell
      expansion termination. Overall, our study underscores the value of using
      computational modeling together with quantitative data to understand root growth.

PMID- 29321186
TI  - Cross-species Comparison of Proteome Turnover Kinetics.
AB  - The constitutive process of protein turnover plays a key role in maintaining
      cellular homeostasis. Recent technological advances in mass spectrometry have
      enabled the measurement of protein turnover kinetics across the proteome.
      However, it is not known if turnover kinetics of individual proteins are highly
      conserved or if they have evolved to meet the physiological demands of individual
      species. Here, we conducted systematic analyses of proteome turnover kinetics in
      primary dermal fibroblasts isolated from eight different rodent species. Our
      results highlighted two trends in the variability of proteome turnover kinetics
      across species. First, we observed a decrease in cross-species correlation of
      protein degradation rates as a function of evolutionary distance. Second, we
      observed a negative correlation between global protein turnover rates and maximum
      lifespan of the species. We propose that by reducing the energetic demands of
      continuous protein turnover, long-lived species may have evolved to lessen the
      generation of reactive oxygen species and the corresponding oxidative damage over
      their extended lifespans.

PMID- 29321181
TI  - Mechanisms of erythrocyte development and regeneration: implications for
      regenerative medicine and beyond.
AB  - Hemoglobin-expressing erythrocytes (red blood cells) act as fundamental metabolic
      regulators by providing oxygen to cells and tissues throughout the body. Whereas
      the vital requirement for oxygen to support metabolically active cells and
      tissues is well established, almost nothing is known regarding how erythrocyte
      development and function impact regeneration. Furthermore, many questions remain
      unanswered relating to how insults to hematopoietic stem/progenitor cells and
      erythrocytes can trigger a massive regenerative process termed 'stress
      erythropoiesis' to produce billions of erythrocytes. Here, we review the cellular
      and molecular mechanisms governing erythrocyte development and regeneration, and
      discuss the potential links between these events and other regenerative
      processes.

PMID- 29321187
TI  - Infection by the Helminth Parasite Fasciola hepatica Requires Rapid Regulation of
      Metabolic, Virulence, and Invasive Factors to Adjust to Its Mammalian Host.
AB  - The parasite Fasciola hepatica infects a broad range of mammals with impunity.
      Following ingestion of parasites (metacercariae) by the host, newly excysted
      juveniles (NEJ) emerge from their cysts, rapidly penetrate the duodenal wall and
      migrate to the liver. Successful infection takes just a few hours and involves
      negotiating hurdles presented by host macromolecules, tissues and micro
      environments, as well as the immune system. Here, transcriptome and proteome
      analysis of ex vivo F. hepatica metacercariae and NEJ reveal the rapidity and
      multitude of metabolic and developmental alterations that take place in order for
      the parasite to establish infection. We found that metacercariae despite being
      encased in a cyst are metabolically active, and primed for infection. Following
      excystment, NEJ expend vital energy stores and rapidly adjust their metabolic
      pathways to cope with their new and increasingly anaerobic environment.
      Temperature increases induce neoblast proliferation and the remarkable up
      regulation of genes associated with growth and development. Cysteine proteases
      synthesized by gastrodermal cells are secreted to facilitate invasion and tissue
      degradation, and tegumental transporters, such as aquaporins, are varied to deal
      with osmotic/salinity changes. Major proteins of the total NEJ secretome include
      proteases, protease inhibitors and anti-oxidants, and an array of
      immunomodulators that likely disarm host innate immune effector cells. Thus, the
      challenges of infection by F. hepatica parasites are met by rapid metabolic and
      physiological adjustments that expedite tissue invasion and immune evasion; these
      changes facilitate parasite growth, development and maturation. Our molecular
      analysis of the critical processes involved in host invasion has identified key
      targets for future drug and vaccine strategies directed at preventing parasite
      infection.

PMID- 29321189
TI  - Gut-brain signaling in energy homeostasis: the unexpected role of microbiota
      derived succinate.
AB  - In the context of the obesity epidemic, dietary fibers that are found essentially
      in fruit and vegetables attract more and more attention, since they exert
      numerous metabolic benefits resulting in the moderation of body weight. Short
      chain fatty acids, such as propionate and butyrate, produced through their
      fermentation by the intestinal microbiota, have long been thought to be the
      mediators of these benefits. In fact, propionate and butyrate were recently shown
      to activate intestinal gluconeogenesis, a function exerting metabolic benefits
      via its capacity of signaling to the brain by gastrointestinal nerves. Recently,
      succinate, the precursor of propionate in the bacterial metabolism, has also been
      shown to exert signaling properties, including the activation of intestinal
      gluconeogenesis.

PMID- 29321188
TI  - Far-Red Light Detection in the Shoot Regulates Lateral Root Development through
      the HY5 Transcription Factor.
AB  - Plants in dense vegetation compete for resources and detect competitors through
      reflection of far-red (FR) light from surrounding plants. This reflection causes
      a reduced red (R):FR ratio, which is sensed through phytochromes. Low R:FR
      induces shade avoidance responses of the shoot and also changes the root system
      architecture, although this has received little attention so far. Here, we
      investigate the molecular mechanisms through which light detection in the shoot
      regulates root development in Arabidopsis thaliana We do so using a combination
      of microscopy, gene expression, and mutant study approaches in a setup that
      allows root imaging without exposing the roots to light treatment. We show that
      low R:FR perception in the shoot decreases the lateral root (LR) density by
      inhibiting LR emergence. This decrease in LR emergence upon shoot FR enrichment
      is regulated by phytochrome-dependent accumulation of the transcription factor
      ELONGATED HYPOCOTYL5 (HY5) in the LR primordia. HY5 regulates LR emergence by
      decreasing the plasma membrane abundance of PIN-FORMED3 and LIKE-AUX1 3 auxin
      transporters. Accordingly, FR enrichment reduces the auxin signal in the
      overlaying cortex cells, and this reduces LR outgrowth. This shoot-to-root
      communication can help plants coordinate resource partitioning under competition
      for light in high density fields.

PMID- 29321190
TI  - Genomic landscape of pancreatic neuroendocrine tumours: the International Cancer
      Genome Consortium.
AB  - Neuroendocrine tumours (NETs) may arise throughout the body and are a highly
      heterogeneous, relatively rare class of neoplasms difficult to study also for the
      lack of disease models. Despite this, knowledge on their molecular alterations
      has expanded in the latest years, also building from genetic syndromes causing
      their onset. Pancreatic NETs (PanNETs) have been among the most studied, and
      research so far has outlined a series of recurring features, as inactivation of
      MEN1, VHL, TSC1/2 genes and hyperactivation of the PI3K/mTOR pathway. Next
      generation sequencing has added new information by showing the key role of
      alternative lengthening of telomeres, driven in a fraction of PanNETs by
      inactivation of ATRX/DAXX. Despite this accumulation of knowledge, single studies
      often relied on few cases or were limited to the DNA, RNA, protein or epigenetic
      level with lack of integrative analysis. The International Cancer Genome
      Consortium aimed at removing these barriers through a strict process of data and
      samples collection, to produce whole-genome integrated analyses for many tumour
      types. The results of this effort on PanNETs have been recently published and,
      while confirming previous observations provide a first snapshot of how
      heterogeneous is the combination of genetic alterations that drive this tumour
      type, yet converging into four pathways whose alteration has been enriched by
      newly discovered mechanisms. While calling for further integration of genetic and
      epigenetic analyses, these data allow to reconcile previous findings in a defined
      frame and may provide clinical research with markers for patients stratification
      and to guide targeted therapy decisions.

PMID- 29321191
TI  - Mortality After Magnetic Resonance Imaging of the Brain in Patients With
      Cardiovascular Implantable Devices.
AB  - BACKGROUND: Use of magnetic resonance imaging (MRI) brain is restricted in
      patients with cardiovascular implantable electronic devices (CIEDs). We proposed
      to determine whether mortality difference exists for patients with non-MRI
      conditional CIEDs undergoing brain MRI compared with controls. METHODS AND
      RESULTS: Retrospective analysis of prospectively collected data was performed to
      compare all-cause mortality in patients with CIEDs undergoing brain MRI (CIED
      MRI) with 3 control groups matched for age, sex, imaging year, and type of CIED:
      (1) no CIED, brain MRI (no-CIED-MRI); (2) CIED, brain computerized tomography
      (CT) scan (CIED-CT); and (3) no CIED, brain CT (no-CIED-CT). The primary outcome
      was a significant difference (P<0.05) between estimated mortality rates.
      Secondary outcomes were changes in device function before and after brain MRI.
      The estimated all-cause mortality at 5 years for the CIED-MRI group [mean age (+/
      SD), 68.2 years (15.3 years); 61.2% men] was not significantly different from
      patients who underwent CT with or without a device (CIED-CT group: hazard ratio,
      0.814; 95% confidence interval, 0.593-1.117; P=0.2; no-CIED-CT group: hazard
      ratio, 1.149; 95% confidence interval, 0.818-1.613; P=0.4). There was a
      significant increase in mortality between CIED-MRI and no-CIED-MRI groups (hazard
      ratio, 1.463; 95% confidence interval, 1.019-2.099; P=0.04). CONCLUSIONS: Brain
      MRI in patients with CIEDs does not carry an increased mortality risk compared
      with brain CT and can be performed with adherence to appropriate procedural
      protocols.

PMID- 29321192
TI  - Transvenous Lead Extraction in Chronic Kidney Disease and Dialysis Patients With
      Infected Cardiac Devices.
AB  - BACKGROUND: Cardiac implantable electronic device infections have been on the
      rise. A high-risk population is that with renal disease, especially dialysis. We
      aimed to assess procedural profiles and clinical outcomes of transvenous lead
      extraction for cardiac implantable electronic device infection based on renal
      disease status. METHODS AND RESULTS: In 1420 consecutive patients undergoing
      transvenous lead extraction of infected cardiac implantable electronic devices
      (1996-2012), we assessed procedural profiles and clinical outcomes in 3 groups:
      normal renal function (group 1, n=1159), renal dysfunction not requiring dialysis
      (group 2, n=163), and dialysis (group 3, n=98). A total of 3182 infected leads
      were extracted. Dialysis patients had shorter lead dwell times and were less
      likely to require transvenous lead extraction tools but as likely to require
      femoral workstations. There were higher overall rates of procedure-related
      complications in dialysis patients (12% versus ~6% in nondialysis) with no
      difference in the major complication rates (P=not significant). Complete
      procedural success rates were 94%, 96%, and 94% in groups 1, 2, and 3,
      respectively (P=not significant). There were 4 intraprocedural deaths in group 1
      versus none in groups 2 and 3. Mortality rates were significantly higher in
      dialysis patients both at 1 and 6 months (P<0.0001 for both). In multivariable
      analyses, dialysis status was independently associated with increased mortality
      risk at 1 and 6 months. Other factors associated with mortality were lead
      material retention, functional (New York Heart Association) class, and occurrence
      of procedural complications. CONCLUSIONS: In patients with cardiac implantable
      electronic device infection, dialysis status did not seem to add complexity to
      transvenous lead extraction but was independently associated with increased
      mortality at 1 and 6 months.

PMID- 29321193
TI  - Cardiac Implantable Electronic Device Infections and Lead Extraction: Are
      Patients With Renal Insufficiency Special?

PMID- 29321195
TI  - Whole-Genome Sequencing of Emerging Invasive Neisseria meningitidis Serogroup W
      in Sweden.
AB  - Invasive disease caused by Neisseria meningitidis serogroup W (MenW) has
      historically had a low incidence in Sweden, with an average incidence of 0.03
      case/100,000 population from 1995 to 2014. In recent years, a significant
      increase in the incidence of MenW has been noted in Sweden, to an average
      incidence of 0.15 case/100,000 population in 2015 to 2016. In 2017 (1 January to
      30 June), 33% of invasive meningococcal disease cases (7/21 cases) were caused by
      MenW. In the present study, all invasive MenW isolates from Sweden collected in
      1995 to June 2017 (n = 86) were subjected to whole-genome sequencing to determine
      the population structure and to compare isolates from Sweden with historical and
      international cases. The increase of MenW in Sweden was determined to be due to
      isolates belonging to the South American sublineage of MenW clonal complex 11,
      namely, the novel U.K. 2013 lineage. This lineage was introduced in Sweden in
      2013 and has since been the dominant lineage of MenW.

PMID- 29321196
TI  - Birt-Hogg-Dube syndrome: spontaneous pneumothorax as a first symptom.
AB  - Birt-Hogg-Dube syndrome (BHDS) is a rare hereditary autosomal dominant condition
      characterised by benign cutaneous lesions, lung cysts, increased risk of
      spontaneous pneumothorax and renal cancer. It shows great heterogenous
      presentation within and between affected families. We report a case of a Danish
      female patient with recurrent pneumothoraces as the first symptom of BHDS. Over
      the years, she developed skin changes, and a family history of skin changes,
      pneumothoraces and renal cancer was discovered. BHDS was suspected, a genetic
      analysis was performed and a pathogenic variation c.1285delC in FLCN gene was
      detected in the patient. As we stated the diagnosis BHDS, we discovered several
      undiagnosed family members all of them now entering a lifelong follow-up
      programme with abdominal imaging because of the increased risk of developing
      renal cancer. BHDS should be known to oncologists, dermatologists and
      pulmonologists as the patients most often present to these medical disciplines.

PMID- 29321197
TI  - Iatrogenic foreign body in an adult with presbyacusis.

PMID- 29321198
TI  - Hepatic amyloidosis: a cause of rapidly progressive jaundice.

PMID- 29321199
TI  - Coats disease with exudative retinal detachment simulating cysticercus cyst:
      misleading ultrasonography!

PMID- 29321194
TI  - Polygenic hazard score to guide screening for aggressive prostate cancer:
      development and validation in large scale cohorts.
AB  - OBJECTIVES: To develop and validate a genetic tool to predict age of onset of
      aggressive prostate cancer (PCa) and to guide decisions of who to screen and at
      what age. DESIGN: Analysis of genotype, PCa status, and age to select single
      nucleotide polymorphisms (SNPs) associated with diagnosis. These polymorphisms
      were incorporated into a survival analysis to estimate their effects on age at
      diagnosis of aggressive PCa (that is, not eligible for surveillance according to
      National Comprehensive Cancer Network guidelines; any of Gleason score >=7, stage
      T3-T4, PSA (prostate specific antigen) concentration >=10 ng/L, nodal metastasis,
      distant metastasis). The resulting polygenic hazard score is an assessment of
      individual genetic risk. The final model was applied to an independent dataset
      containing genotype and PSA screening data. The hazard score was calculated for
      these men to test prediction of survival free from PCa. SETTING: Multiple
      institutions that were members of international PRACTICAL consortium.
      PARTICIPANTS: All consortium participants of European ancestry with known age,
      PCa status, and quality assured custom (iCOGS) array genotype data. The
      development dataset comprised 31 747 men; the validation dataset comprised 6411
      men. MAIN OUTCOME MEASURES: Prediction with hazard score of age of onset of
      aggressive cancer in validation set. RESULTS: In the independent validation set,
      the hazard score calculated from 54 single nucleotide polymorphisms was a highly
      significant predictor of age at diagnosis of aggressive cancer (z=11.2, P<10-16).
      When men in the validation set with high scores (>98th centile) were compared
      with those with average scores (30th-70th centile), the hazard ratio for
      aggressive cancer was 2.9 (95% confidence interval 2.4 to 3.4). Inclusion of
      family history in a combined model did not improve prediction of onset of
      aggressive PCa (P=0.59), and polygenic hazard score performance remained high
      when family history was accounted for. Additionally, the positive predictive
      value of PSA screening for aggressive PCa was increased with increasing polygenic
      hazard score. CONCLUSIONS: Polygenic hazard scores can be used for personalised
      genetic risk estimates that can predict for age at onset of aggressive PCa.

PMID- 29321200
TI  - Bilateral haemorrhagic basal ganglia infarction associated with early-onset group
      B streptococcus meningitis.
AB  - A 2-day-old infant presented with poor feeding and grunting. Investigations
      revealed a raised C reactive protein of 164. Full septic screen was done, which
      subsequently confirmed a diagnosis of group B streptococcus meningitis. Baby was
      apyrexial and haemodynamically stable. There were no obvious neurological
      manifestations, and a routine cranial ultrasound scan was done, which revealed
      echogenic changes in the basal ganglia and thalami. MRI brain showed extensive
      haemorrhagic infarction within the lentiform and caudate nuclei with involvement
      of both posterior limbs of the internal capsule. This was followed by
      triventricular hydrocephalus needing shunt procedure. The clinical course was
      complicated by infantile spasms, which were treated with vigabatrin and steroids
      and subsequent global developmental delay and cerebral palsy.

PMID- 29321201
TI  - Brain abscess in a patient with chronic sinusitis.

PMID- 29321203
TI  - Acute-on-chronic mesenteric ischaemia by early and diffuse atherosclerosis in a
      young adult patient.

PMID- 29321202
TI  - Extraocular muscle cysticercosis: never skip steroids.

PMID- 29321204
TI  - Larval infestation of chronic ischaemic leg ulcer.

PMID- 29321205
TI  - Advantages of a distant cellulase catalytic base.
AB  - The inverting glycoside hydrolase Trichoderma reesei (Hypocrea jecorina) Cel6A is
      a promising candidate for protein engineering for more economical production of
      biofuels. Until recently, its catalytic mechanism had been uncertain: The best
      candidate residue to serve as a catalytic base, Asp-175, is farther from the
      glycosidic cleavage site than in other glycoside hydrolase enzymes. Recent
      unbiased transition path sampling simulations revealed the hydrolytic mechanism
      for this more distant base, employing a water wire; however, it is not clear why
      the enzyme employs a more distant catalytic base, a highly conserved feature
      among homologs across different kingdoms. In this work, we describe molecular
      dynamics simulations designed to uncover how a base with a longer side chain, as
      in a D175E mutant, affects procession and active site alignment in the Michaelis
      complex. We show that the hydrogen bond network is tuned to the shorter aspartate
      side chain, and that a longer glutamate side chain inhibits procession as well as
      being less likely to adopt a catalytically productive conformation. Furthermore,
      we draw comparisons between the active site in Trichoderma reesei Cel6A and
      another inverting, processive cellulase to deduce the contribution of the water
      wire to the overall enzyme function, revealing that the more distant catalytic
      base enhances product release. Our results can inform efforts in the study and
      design of enzymes by demonstrating how counterintuitive sacrifices in chemical
      reactivity can have worthwhile benefits for other steps in the catalytic cycle.

PMID- 29321206
TI  - Revealing the protein propionylation activity of the histone acetyltransferase
      MOF (males absent on the first).
AB  - Short-chain acylation of lysine residues has recently emerged as a group of
      reversible posttranslational modifications in mammalian cells. The diversity of
      acylation further broadens the landscape and complexity of the proteome.
      Identification of regulatory enzymes and effector proteins for lysine acylation
      is critical to understand functions of these novel modifications at the molecular
      level. Here, we report that the MYST family of lysine acetyltransferases (KATs)
      possesses strong propionyltransferase activity both in vitro and in cellulo
      Particularly, the propionyltransferase activity of MOF, MOZ, and HBO1 is as
      strong as their acetyltransferase activity. Overexpression of MOF in human
      embryonic kidney 293T cells induced significantly increased propionylation in
      multiple histone and non-histone proteins, which shows that the function of MOF
      goes far beyond its canonical histone H4 lysine 16 acetylation. We also resolved
      the X-ray co-crystal structure of MOF bound with propionyl-coenzyme A, which
      provides a direct structural basis for the propionyltransferase activity of the
      MYST KATs. Our data together define a novel function for the MYST KATs as lysine
      propionyltransferases and suggest much broader physiological impacts for this
      family of enzymes.

PMID- 29321209
TI  - Issues and challenges for research in major trauma.
AB  - The starting point for evidence-based guidelines is the systematic review and
      critical appraisal of the relevant literature. This review highlights the risk of
      bias identified while critically appraising the evidence to inform the National
      Institute of Health and Care Excellence guideline on the assessment and initial
      management of major trauma.

PMID- 29321208
TI  - Engineered synthetic antibodies as probes to quantify the energetic contributions
      of ligand binding to conformational changes in proteins.
AB  - Conformational changes in proteins due to ligand binding are ubiquitous in
      biological processes and are integral to many biological systems. However, it is
      often challenging to link ligand-induced conformational changes to a resulting
      biological function because it is difficult to distinguish between the energetic
      components associated with ligand binding and those due to structural
      rearrangements. Here, we used a unique approach exploiting conformation-specific
      and regio-specific synthetic antibodies (sABs) to probe the energetic
      contributions of ligand binding to conformation changes. Using maltose-binding
      protein (MBP) as a model system, customized phage-display selections were
      performed to generate sABs that stabilize MBP in different conformational states,
      modulating ligand-binding affinity in competitive, allosteric, or peristeric
      manners. We determined that the binding of a closed conformation-specific sAB
      (sAB-11M) to MBP in the absence of maltose is entropically driven, providing new
      insight into designing antibody-stabilized protein interactions. Crystal
      structures of sABs bound to MBP, together with biophysical data, delineate the
      basis of free energy differences between different conformational states and
      confirm the use of the sABs as energy probes for dissecting enthalpic and
      entropic contributions to conformational transitions. Our work provides a
      foundation for investigating the energetic contributions of distinct
      conformational dynamics to specific biological outputs. We anticipate that our
      approach also may be valuable for analyzing the energy landscapes of regulatory
      proteins controlling biological responses to environmental changes.

PMID- 29321207
TI  - Aberrantly high expression of the CUB and zona pellucida-like domain-containing
      protein 1 (CUZD1) in mammary epithelium leads to breast tumorigenesis.
AB  - The peptide hormone prolactin (PRL) and certain members of the epidermal growth
      factor (EGF) family play central roles in mammary gland development and
      physiology, and their dysregulation has been implicated in mammary tumorigenesis.
      Our recent studies have revealed that the CUB and zona pellucida-like domain
      containing protein 1 (CUZD1) is a critical factor for PRL-mediated activation of
      the transcription factor STAT5 in mouse mammary epithelium. Of note, CUZD1
      controls production of a specific subset of the EGF family growth factors and
      consequent activation of their receptors. Here, we found that consistent with
      this finding, CUZD1 overexpression in non-transformed mammary epithelial HC11
      cells increases their proliferation and induces tumorigenic characteristics in
      these cells. When introduced orthotopically in mouse mammary glands, these cells
      formed adenocarcinomas, exhibiting elevated levels of STAT5 phosphorylation and
      activation of the EGF signaling pathway. Selective blockade of STAT5
      phosphorylation by pimozide, a small-molecule inhibitor, markedly reduced the
      production of the EGF family growth factors and inhibited PRL-induced tumor cell
      proliferation in vitro Pimozide administration to mice also suppressed CUZD1
      driven mammary tumorigenesis in vivo Analysis of human MCF7 breast cancer cells
      indicated that CUZD1 controls the production of the same subset of EGF family
      members in these cells as in the mouse. Moreover, pimozide treatment reduced the
      proliferation of these cancer cells. Collectively, these findings indicate that
      overexpression of CUZD1, a regulator of growth factor pathways controlled by PRL
      and STAT5, promotes mammary tumorigenesis. Blockade of the STAT5 signaling
      pathway downstream of CUZD1 may offer a therapeutic strategy for managing these
      breast tumors.

PMID- 29321210
TI  - The Immune Checkpoint Modulator OX40 and Its Ligand OX40L in NK-Cell
      Immunosurveillance and Acute Myeloid Leukemia.
AB  - The TNF receptor family member OX40 promotes activation and proliferation of T
      cells, which fuels efforts to modulate this immune checkpoint to reinforce
      antitumor immunity. Besides T cells, NK cells are a second cytotoxic lymphocyte
      subset that contributes to antitumor immunity, particularly in leukemia.
      Accordingly, these cells are being clinically evaluated for cancer treatment
      through multiple approaches, such as adoptive transfer of ex vivo expanded
      polyclonal NK cells (pNKC). Here, we analyzed whether and how OX40 and its ligand
      (OX40L) influence NK-cell function and antileukemia reactivity. We report that
      OX40 is expressed on leukemic blasts in a substantial percentage of patients with
      acute myeloid leukemia (AML) and that OX40 can, after stimulation with agonistic
      OX40 antibodies, mediate proliferation and release of cytokines that act as
      growth and survival factors for the leukemic cells. We also demonstrate that pNKC
      differentially express OX40L, depending on the protocol used for their
      generation. OX40L signaling promoted NK-cell activation, cytokine production, and
      cytotoxicity, and disruption of OX40-OX40L interaction impaired pNKC reactivity
      against primary AML cells. Together, our data implicate OX40/OX40L in disease
      pathophysiology of AML and in NK-cell immunosurveillance. Our findings indicate
      that effects of the OX40-OX40L receptor-ligand system in other immune cell
      subsets and also malignant cells should be taken into account when developing
      OX40-targeted approaches for cancer immunotherapy. Cancer Immunol Res; 6(2); 209
      21. (c)2018 AACR.

PMID- 29321211
TI  - Pathophysiology of Degenerative Mitral Regurgitation: New 3-Dimensional Imaging
      Insights.
AB  - Despite its high prevalence, little is known about mechanisms of mitral
      regurgitation in degenerative mitral valve disease apart from the leaflet
      prolapse itself. Mitral valve is a complex structure, including mitral annulus,
      mitral leaflets, papillary muscles, chords, and left ventricular walls. All these
      structures are involved in physiological and pathological functioning of this
      valvuloventricular complex but up to now were difficult to analyze because of
      inherent limitations of 2-dimensional imaging. The advent of 3-dimensional
      echocardiography, computed tomography, and cardiac magnetic resonance imaging
      overcoming these limitations provides new insights into mechanistic analysis of
      degenerative mitral regurgitation. This review will detail the contribution of
      quantitative and qualitative dynamic analysis of mitral annulus and mitral
      leaflets by new imaging methods in the understanding of degenerative mitral
      regurgitation pathophysiology.

PMID- 29321212
TI  - Prognostic Value of Right Ventricular Dysfunction in Heart Failure With Reduced
      Ejection Fraction: Superiority of Longitudinal Strain Over Tricuspid Annular
      Plane Systolic Excursion.
AB  - BACKGROUND: In heart failure (HF) with reduced ejection fraction, right
      ventricular (RV) impairment, as defined by reduced tricuspid annular plane
      systolic excursion, is a predictor of poor outcome. However, peak longitudinal
      strain of RV free wall (RVFWS) has been recently proposed as a more accurate and
      sensitive tool to evaluate RV function. Accordingly, we investigated whether
      RVFWS could help refine prognosis of patients with HF with reduced ejection
      fraction in whom tricuspid annular plane systolic excursion is still preserved.
      METHODS AND RESULTS: A total of 200 patients with HF with reduced ejection
      fraction (age, 66+/-11 years; ejection fraction, 30+/-7%) with preserved
      tricuspid annular plane systolic excursion (>16 mm) underwent RV function
      assessment using speckle-tracking echocardiography to measure peak RVFWS. After a
      median follow-up period of 28 months, 62 (31%) patients reached the primary
      composite end point of all-cause death/HF rehospitalization. Median RVFWS was 
      19.3% (interquartile range, -23.3% to -15.0%). By lasso-penalized Cox-hazard
      model, RVFWS was an independent predictor of outcome, along with Eplerenone in
      Mild Patients Hospitalization and Survival Study in Heart Failure-HF score, Echo
      HF score, and severe mitral regurgitation. The best cutoff value of RVFWS for
      prediction of outcome was -15.3% (area under the curve, 0.68; P<0.001;
      sensitivity, 50%; specificity, 80%). In 50 patients (25%), RVFWS was impaired
      (ie, >=-15.3%); event rate (per 100 patients per year) was greater in them than
      in patients with RVFWS <-15.3% (29.5% [95% confidence interval, 20.4-42.7] versus
      9.4% [95% confidence interval, 6.7-13.1]; P<0.001). RVFWS yielded a significant
      net reclassification improvement (0.584 at 3 years; P<0.001), with 68% of
      nonevents correctly reclassified. CONCLUSIONS: In patients with HF with reduced
      ejection fraction with preserved tricuspid annular plane systolic excursion, RV
      free-wall strain provides incremental prognostic information and improved risk
      stratification.

PMID- 29321213
TI  - 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomographic Imaging
      Detects Aortic Wall Inflammation in Patients With Repaired Coarctation of Aorta.

PMID- 29321214
TI  - 18F-Flurodeoxyglucose and 18F-Sodium Fluoride Positron Emission
      Tomography/Computed Tomography Imaging of Arterial and Cutaneous Alterations in
      Pseudoxanthoma Elasticum.

PMID- 29321215
TI  - Right Ventricular Function in Heart Failure: The Long and Short of Free Wall
      Motion Versus Deformation Imaging.

PMID- 29321217
TI  - Erratum. Factors Associated With Diabetes-Specific Health-Related Quality of Life
      in Youth With Type 1 Diabetes: The Global TEENs Study. Diabetes Care 2017;40:1002
      1009.

PMID- 29321218
TI  - Non-uniform relationship between salt status and aldosterone activity in patients
      with chronic kidney disease.
AB  - BACKGROUND: Hypertension is prevalent in chronic kidney disease (CKD). Studies
      suggest that reduction in dietary salt intake reduces blood pressure (BP). We
      studied relationships between salt intake, BP and renin-angiotensin system
      regulation in order to establish if it is disordered in CKD. METHODS: Mechanistic
      crossover study of CKD patients versus non-CKD controls. Participants underwent
      modified saline suppression test prior to randomization to either low or high
      salt diet for 5 days and then crossed over to the alternate diet. Angiotensin-II
      stimulation testing was performed in both salt states. BP, urea and electrolytes,
      and plasma aldosterone concentration (PAC) were measured. RESULTS: Twenty-seven
      subjects were recruited (12 CKD, 15 control). There was no difference in age and
      baseline BP between the groups. Following administration of intravenous saline,
      systolic BP increased in CKD but not controls (131 +/- 16 to 139 +/- 14 mmHg,
      P=0.016 vs 125 +/- 20 to 128 +/- 22 mmHg, P=0.38). Median PAC reduced from 184
      (124,340) to 95 (80,167) pmol in controls (P=0.003), but failed to suppress in
      CKD (230 (137,334) to 222 (147,326) pmol (P=0.17)). Following dietary salt
      modification, there was no change in BP in either group. Median PAC was lower
      following high salt compared with low salt diet in CKD and controls. There was a
      comparable increase in systolic BP in response to angiotensin-II in both groups.
      DISCUSSION: We demonstrate dysregulation of aldosterone in CKD in response to
      salt loading with intravenous saline, but not to dietary salt modification.

PMID- 29321219
TI  - What can the lived experience of participating in risky HIV cure-related studies
      establish?
AB  - This response to Gail Henderson et al argues that they were right that
      interviewees' appraisals of cure study participation should inform (future)
      protocol review decisions, but wrong to take these appraisals at face value.

PMID- 29321220
TI  - Against proportional shortfall as a priority-setting principle.
AB  - As the demand for healthcare rises, so does the need for priority setting in
      healthcare. In this paper, I consider a prominent priority-setting principle:
      proportional shortfall. My purpose is to argue that proportional shortfall, as a
      principle, should not be adopted. My key criticism is that proportional shortfall
      fails to consider past health.Proportional shortfall is justified as it
      supposedly balances concern for prospective health while still accounting for
      lifetime health, even though past health is deemed irrelevant. Accounting for
      this lifetime perspective means that the principle may indirectly consider past
      health by accounting for how far an individual is from achieving a complete,
      healthy life. I argue that proportional shortfall does not account for this
      lifetime perspective as it fails to incorporate the fair innings argument as
      originally claimed, undermining its purported justification.I go on to
      demonstrate that the case for ignoring past health is weak, and argue that past
      health is at least sometimes relevant for priority-setting decisions.
      Specifically, when an individual's past health has a direct impact on current or
      future health, and when one individual has enjoyed significantly more healthy
      life years than another.Finally, I demonstrate that by ignoring past illnesses,
      even those entirely unrelated to their current illness, proportional shortfall
      can lead to instances of double jeopardy, a highly problematic implication. These
      arguments give us reason to reject proportional shortfall.

PMID- 29321221
TI  - Is consistency overrated?

PMID- 29321223
TI  - WESTERN MEDICAL RESEARCH CONFERENCE (FORMERLY WESTERN REGIONAL MEETING).

PMID- 29321227
TI  - Neurofilament light, biomarkers, and Charcot-Marie-Tooth disease.

PMID- 29321225
TI  - Humanized TREM2 mice reveal microglia-intrinsic and -extrinsic effects of R47H
      polymorphism.
AB  - Alzheimer's disease (AD) is a neurodegenerative disease that causes late-onset
      dementia. The R47H variant of the microglial receptor TREM2 triples AD risk in
      genome-wide association studies. In mouse AD models, TREM2-deficient microglia
      fail to proliferate and cluster around the amyloid-beta plaques characteristic of
      AD. In vitro, the common variant (CV) of TREM2 binds anionic lipids, whereas R47H
      mutation impairs binding. However, in vivo, the identity of TREM2 ligands and
      effect of the R47H variant remain unknown. We generated transgenic mice
      expressing human CV or R47H TREM2 and lacking endogenous TREM2 in the 5XFAD AD
      model. Only the CV transgene restored amyloid-beta-induced microgliosis and
      microglial activation, indicating that R47H impairs TREM2 function in vivo.
      Remarkably, soluble TREM2 was found on neurons and plaques in CV- but not R47H
      expressing 5XFAD brains, although in vitro CV and R47H were shed similarly via
      Adam17 proteolytic activity. These results demonstrate that TREM2 interacts with
      neurons and plaques duing amyloid-beta accumulation and R47H impairs this
      interaction.

PMID- 29321226
TI  - The association of neurologists with headache health care utilization and costs.
AB  - OBJECTIVE: To determine the association of a neurologist visit with headache
      health care utilization and costs. METHODS: Utilizing a large privately insured
      health care claims database, we identified patients with an incident headache
      diagnosis (ICD-9 codes 339.xx, 784.0x, 306.81) with at least 5 years follow-up.
      Patients with a subsequent neurologist visit were matched to controls without a
      neurologist visit using propensity score matching, accounting for 54 potential
      confounders and regional variation in neurologist density. Co-primary outcomes
      were emergency department (ED) visits and hospitalizations for headache.
      Secondary outcomes were quality measures (abortive, prophylactic, and opioid
      prescriptions) and costs (total, headache-related, and non-headache-related).
      Generalized estimating equations assessed differences in longitudinal outcomes
      between cases and controls. RESULTS: We identified 28,585 cases and 57,170
      controls. ED visits did not differ between cases and controls (p = 0.05).
      Hospitalizations were more common in cases in year 0-1 (0.2%, 95% confidence
      interval [CI] 0.2%-0.3% vs 0.01%, 95% CI 0.01%-0.02%; p < 0.01), with minimal
      differences in subsequent years. Costs (including non-headache-related costs) and
      high-quality and low-quality medication utilization were higher in cases in the
      first year and decreased toward control costs in subsequent years with small
      differences persisting over 5 years. Opioid prescriptions increased over time in
      both cases and controls. CONCLUSION: Compared with those without a neurologist,
      headache patients who visit neurologists had a transient increase in
      hospitalizations, but the same ED utilization. Confounding by severity is the
      most likely explanation given the non-headache-related cost trajectory. Claims
      based risk adjustment will likely underestimate disease severity of headache
      patients seen by neurologists.

PMID- 29321228
TI  - Comment: Tau CSF proteins for diagnosis but tau PET imaging for AD diagnosis and
      staging.

PMID- 29321224
TI  - Reconsidering an active role for G-actin in cytoskeletal regulation.
AB  - Globular (G)-actin, the actin monomer, assembles into polarized filaments that
      form networks that can provide structural support, generate force and organize
      the cell. Many of these structures are highly dynamic and to maintain them, the
      cell relies on a large reserve of monomers. Classically, the G-actin pool has
      been thought of as homogenous. However, recent work has shown that actin monomers
      can exist in distinct groups that can be targeted to specific networks, where
      they drive and modify filament assembly in ways that can have profound effects on
      cellular behavior. This Review focuses on the potential factors that could create
      functionally distinct pools of actin monomers in the cell, including differences
      between the actin isoforms and the regulation of G-actin by monomer binding
      proteins, such as profilin and thymosin beta4. Owing to difficulties in studying
      and visualizing G-actin, our knowledge over the precise role that specific actin
      monomer pools play in regulating cellular actin dynamics remains incomplete.
      Here, we discuss some of these unanswered questions and also provide a summary of
      the methodologies currently available for the imaging of G-actin.

PMID- 29321230
TI  - Progressive multifocal leukoencephalopathy: Are you aware of it?

PMID- 29321229
TI  - The national incidence of PML in Sweden, 1988-2013.
AB  - OBJECTIVE: To investigate the incidence of progressive multifocal
      leukoencephalopathy (PML) and patient characteristics in Sweden between 1988 and
      2013. METHODS: All PML diagnoses in Sweden between 1988 and 2013 were identified
      in the National Patient Register. Information to validate the diagnosis and
      patient characteristics was obtained from medical records. RESULTS: Medical
      record review classified 108 out of 250 patients (43%) as definite (n = 84),
      probable (n = 4), or possible (n = 20) PML according to diagnostic criteria.
      Accurate diagnoses were more common in records obtained from neurology
      departments (82% of patients seen in neurology departments) compared with other
      departments (31%) (p < 0.001). The incidence of PML increased from a largely
      stable level at 0.026 (95% confidence interval [CI] 0.021-0.031) per 100,000
      individuals per year during 1988-2010 to 0.11 (95% CI 083-0.137) during 2011
      2013, during which time there was a notable increase (p < 0.001). Hematologic
      malignancies (n = 34), HIV/AIDS (n = 33), and autoimmune disease (n = 23) were
      the most common underlying diseases. Treatment with a monoclonal antibody prior
      to PML diagnosis was identified in 26 patients. CONCLUSION: An increased
      incidence of PML in Sweden was observed and coincided with the prior use of
      monoclonal antibody treatment. The high level of misdiagnosis emphasizes the
      importance of immediate contact with a neurology center upon suspicion of PML.

PMID- 29321231
TI  - Chronic traumatic encephalopathy in an epilepsy surgery cohort: Clinical and
      pathologic findings.
AB  - OBJECTIVE: To determine the occurrence of chronic traumatic encephalopathy (CTE)
      in young adult patients undergoing epilepsy surgery. METHODS: Ten patients who
      underwent epilepsy surgery were randomly selected for this retrospective study.
      The patients were 18-45 years of age, had preoperative neuropsychological
      evaluation, and had 1 year postoperative follow-up. Microscopic sections from
      resections were evaluated for the presence of CTE with standard stains and
      antibodies to tau (clone AT8). RESULTS: The median age at resection was 32.5
      years (range 23-43) and the median duration of seizures was 23.5 years (range 3
      28). Eight had a history of head injury. Preoperative neuropsychological testing
      showed mild to moderate cognitive impairment in 8 patients (80%). Pathologic
      examination in one patient showed focal sparse tau-immunoreactive lesions along
      descending rami and cortical gyral depths of the resected frontal lobe. Nine
      patients had no evidence of CTE. All focal cortical resections showed variable
      subpial and subcortical gliosis commonly identified in patients with chronic
      seizure disorders. CONCLUSIONS: The present small retrospective observational
      study suggests that CTE may occur, but appears uncommon, in young adult patients
      undergoing surgical treatment for drug-resistant focal epilepsy. The significance
      of these findings requires further investigation to define the relative
      importance of tau accumulation in younger adult patients with drug-resistant
      focal epilepsy and cognitive decline.

PMID- 29321232
TI  - Hypermyelination of the left auditory cortex in developmental dyslexia.
AB  - OBJECTIVE: Cortical malformations are documented postmortem in speech processing
      areas of the dyslexic human brain. The goal of this pilot study was to find out
      if such anatomic anomalies can be detected noninvasively and in vivo. METHODS: We
      developed a reconstruction of left perisylvian cortex profiles at a resolution of
      400 MUm using T1 data acquired with ultra-high-field MRI at 7T. Cortical
      thickness, myelinated cortical thickness, and layer-wise myelination were then
      compared in 6 men with developmental dyslexia and 6 healthy controls matched for
      age, sex, handedness, education level, and nonverbal IQ. RESULTS: Compared to
      healthy controls, dyslexic individuals showed comparable cortical thickness
      (t[1,10] = 1.98, p = 0.311) but significantly increased myelinated cortical
      thickness ratio (t[1,10] = 3.85, p = 0.013, familywise error-corrected, Cohen d =
      2.03), resulting in an area under the receiver operator characteristic curve of
      0.944 (p = 0.010, standard error 0.067, 95% confidence interval 0.814-1).
      Moreover, T1 relaxation, especially in layer IV of the left auditory cortex, was
      also significantly increased (t[1,10] = 3.32, p = 0.043, familywise-error
      corrected, Cohen d = 1.67). CONCLUSIONS: Our findings provide critical insights
      into the neurobiological manifestation of the most common learning disorder and
      suggest that our approach might also shed new light on other neurodevelopmental
      disorders associated with cortical abnormalities.

PMID- 29321233
TI  - Effect of psychostimulants on blood pressure profile and endothelial function in
      narcolepsy.
AB  - OBJECTIVE: To assess the effect of psychostimulant treatments on the 24-hour
      blood pressure (BP) profile of patients with narcolepsy type 1 (NT1). METHODS:
      Heart rate (HR) and BP were monitored for 24 hours and morning endothelial
      function was evaluated in 160 consecutive patients with NT1: 68 untreated (41
      male, median age 34.9 years), 54 treated (32 male, median age 40.9 years), and 38
      evaluated twice (21 male, median age 32 years), before and during treatment.
      RESULTS: Patients treated for NT1 showed higher 24-hour, daytime, and nighttime
      diastolic BP and HR values compared with the untreated group. Similarly, HR as
      well as 24-hour and daytime systolic BP were increased during treatment in the
      group evaluated twice. The combination of stimulant and anticataplectic drugs
      showed a synergistic effect on BP, without differences among stimulant
      categories. Based on 24-hour BP monitoring, hypertension was diagnosed in 58% of
      treated patients and in 40.6% of untreated patients. After adjustments for age,
      sex, and body mass index, the percentage of REM sleep remained associated with 24
      hour hypertension in untreated and treated patients. Endothelial function was
      comparable in treated and untreated patients. CONCLUSIONS: The finding that
      patients with NT1 treated with psychostimulants have higher diastolic BP and HR
      than untreated patients suggests an increased long-term risk of cardiovascular
      diseases that requires careful follow-up and specific management.

PMID- 29321234
TI  - Plasma neurofilament light chain concentration in the inherited peripheral
      neuropathies.
AB  - OBJECTIVE: To perform a cross-sectional study to determine whether plasma
      neurofilament light chain (NfL) concentration is elevated in patients with
      Charcot-Marie-Tooth disease (CMT) and if it correlates with disease severity.
      METHODS: Blood samples were collected from 75 patients with CMT and 67 age
      matched healthy controls over a 1-year period. Disease severity was measured
      using the Rasch modified CMT Examination and neuropathy scores. Plasma NfL
      concentration was measured using an in-house-developed Simoa assay. RESULTS:
      Plasma NfL concentration was significantly higher in patients with CMT (median
      26.0 pg/mL) compared to healthy controls (median 14.6 pg/mL, p < 0.0001) and
      correlated with disease severity as measured using the Rasch modified CMT
      examination (r = 0.43, p < 0.0001) and neuropathy (r = 0.37, p = 0.044) scores.
      Concentrations were also significantly higher when subdividing patients by
      genetic subtype (CMT1A, SPTLC1, and GJB1) or into demyelinating or axonal forms
      compared to healthy controls. CONCLUSION: There are currently no validated blood
      biomarkers for peripheral neuropathy. The significantly raised plasma NfL
      concentration in patients with CMT and its correlation with disease severity
      suggest that plasma NfL holds promise as a biomarker of disease activity, not
      only for inherited neuropathies but for peripheral neuropathy in general.

PMID- 29321222
TI  - Multiple Inhibitory Factors Act in the Late Phase of HIV-1 Replication: a
      Systematic Review of the Literature.
AB  - The use of lentiviral vectors for therapeutic purposes has shown promising
      results in clinical trials. The ability to produce a clinical-grade vector at
      high yields remains a critical issue. One possible obstacle could be cellular
      factors known to inhibit human immunodeficiency virus (HIV). To date, five HIV
      restriction factors have been identified, although it is likely that more factors
      are involved in the complex HIV-cell interaction. Inhibitory factors that have an
      adverse effect but do not abolish virus production are much less well described.
      Therefore, a gap exists in the knowledge of inhibitory factors acting late in the
      HIV life cycle (from transcription to infection of a new cell), which are
      relevant to the lentiviral vector production process. The objective was to review
      the HIV literature to identify cellular factors previously implicated as
      inhibitors of the late stages of lentivirus production. A search for publications
      was conducted on MEDLINE via the PubMed interface, using the keyword sequence
      "HIV restriction factor" or "HIV restriction" or "inhibit HIV" or "repress HIV"
      or "restrict HIV" or "suppress HIV" or "block HIV," with a publication date up to
      31 December 2016. Cited papers from the identified records were investigated, and
      additional database searches were performed. A total of 260 candidate inhibitory
      factors were identified. These factors have been identified in the literature as
      having a negative impact on HIV replication. This study identified hundreds of
      candidate inhibitory factors for which the impact of modulating their expression
      in lentiviral vector production could be beneficial.

PMID- 29321235
TI  - Comparing 18F-AV-1451 with CSF t-tau and p-tau for diagnosis of Alzheimer
      disease.
AB  - OBJECTIVE: To compare PET imaging of tau pathology with CSF measurements (total
      tau [t-tau] and phosphorylated tau [p-tau]) in terms of diagnostic performance
      for Alzheimer disease (AD). METHODS: We compared t-tau and p-tau and 18F-AV-1451
      in 30 controls, 14 patients with prodromal AD, and 39 patients with Alzheimer
      dementia, recruited from the Swedish BioFINDER study. All patients with AD
      (prodromal and dementia) were screened for amyloid positivity using CSF beta
      amyloid 42. Retention of 18F-AV-1451 was measured in a priori specified regions,
      selected for known associations with tau pathology in AD. RESULTS: Retention of
      18F-AV-1451 was markedly elevated in Alzheimer dementia and moderately elevated
      in prodromal AD. CSF t-tau and p-tau was increased to similar levels in both AD
      dementia and prodromal AD. 18F-AV-1451 had very good diagnostic performance for
      Alzheimer dementia (area under the receiver operating characteristic curve
      [AUROC] ~1.000), and was significantly better than t-tau (0.876), p-tau (0.890),
      hippocampal volume (0.824), and temporal cortical thickness (0.860). For
      prodromal AD, there were no significant AUROC differences between CSF tau and 18F
      AV-1451 measures (0.836-0.939), but MRI measures had lower AUROCs (0.652-0.769).
      CONCLUSIONS: CSF tau and 18F-AV-1451 have equal performance in early clinical
      stages of AD, but 18F-AV-1451 is superior in the dementia stage, and exhibits
      close to perfect diagnostic performance for mild to moderate AD. CLASSIFICATION
      OF EVIDENCE: This study provides Class III evidence that CSF tau and 18F-AV-1451
      PET have similar performance in identifying early AD, and that 18F-AV-1451 PET is
      superior to CSF tau in identifying mild to moderate AD.

PMID- 29321236
TI  - Midregional proatrial natriuretic peptide improves risk stratification after
      ischemic stroke.
AB  - OBJECTIVE: To validate midregional proatrial natriuretic peptide (MR-proANP) for
      outcome prediction and diagnosis of cardioembolic stroke etiology compared to
      established clinical variables. METHODS: In this prospective multicenter cohort
      study, we quantified MR-proANP levels in ischemic stroke patients within 24 hours
      of onset. Primary outcome measures were 90-day mortality, unfavorable functional
      outcome (modified Rankin Scale score >2), and cardioembolic stroke etiology
      diagnosed during hospitalization. RESULTS: Of 788 included patients, 783
      completed their 90-day follow-up, and 118 patients (15%) died. After full
      adjustment, MR-proANP levels were associated with 90-day mortality (adjusted
      hazard ratio 6.12, 95% confidence interval [CI] 2.36-15.84, p = 0.01) and
      functional outcome (adjusted odds ratio [aOR] 2.46, 95% CI 1.05-5.74, p = 0.038).
      For mortality prediction, adding MR-proANP to the regression model increased its
      discriminatory accuracy, and the continuous net reclassification index (cNRI) was
      49% (95% CI 26%-78%, p < 0.001). For functional outcome, there was no significant
      improvement in discrimination or reclassification. Cardioembolic stroke etiology
      and the diagnosis of atrial fibrillation at hospital discharge were associated
      with MR-proANP with an aOR of 2.10 (95% CI 1.11-3.97, p = 0.02) and 18.35 (95% CI
      7.94-42.45, p < 0.001), respectively. The cNRI of MR-proANP for cardioembolic
      stroke etiology was not significant, as opposed to atrial fibrillation (78%, 95%
      CI 60%-89%, p < 0.001). MR-proANP levels >=289 pmol/L had a specificity of 86%
      and sensitivity of 48% for the diagnosis of atrial fibrillation. CONCLUSION: MR
      proANP is a newly validated blood biomarker providing additional prognostic
      information for mortality after stroke. Higher MR-proANP levels were associated
      with cardioembolic stroke etiology and, even more strongly, atrial fibrillation.

PMID- 29321238
TI  - An open-label trial of JAK 1/2 blockade in progressive IFIH1-associated
      neuroinflammation.

PMID- 29321237
TI  - Differences in risk factors for 3 types of stroke: UK prospective study and meta
      analyses.
AB  - OBJECTIVE: To compare associations of behavioral and related factors for incident
      subarachnoid hemorrhage and intracerebral hemorrhage and ischemic stroke.
      METHODS: A total of 712,433 Million Women Study participants without prior
      stroke, heart disease, or cancer reported behavioral and related factors at
      baseline (1999-2007) and were followed up by record linkage to national hospital
      admission and death databases. Cox regression yielded adjusted relative risks
      (RRs) by type of stroke. Heterogeneity was assessed with chi2 tests. When
      appropriate, meta-analyses were done of published prospective studies. RESULTS:
      After 12.9 (SD 2.6) years of follow-up, 8,128 women had an incident ischemic
      stroke, 2,032 had intracerebral hemorrhage, and 1,536 had subarachnoid
      hemorrhage. In women with diabetes mellitus, the risk of ischemic stroke was
      substantially increased (RR 2.01, 95% confidence interval [CI] 1.84-2.20), risk
      of intracerebral hemorrhage was increased slightly (RR 1.31, 95% CI 1.04-1.65),
      but risk of subarachnoid hemorrhage was reduced (RR 0.43, 95% CI 0.26-0.69)
      (heterogeneity by stroke type, p < 0.0001). Stroke incidence was greater in women
      who rated their health as poor/fair compared to those who rated their health as
      excellent/good (RR 1.36, 95% CI 1.30-1.42). Among 565,850 women who rated their
      heath as excellent/good, current smokers were at an increased risk of all 3
      stroke types, (although greater for subarachnoid hemorrhage [>=15 cigarettes/d vs
      never smoker, RR 4.75, 95% CI 4.12-5.47] than for intracerebral hemorrhage [RR
      2.30, 95% CI 1.94-2.72] or ischemic stroke [RR 2.50, 95% CI 2.29-2.72];
      heterogeneity p < 0.0001). Obesity was associated with an increased risk of
      ischemic stroke and a decreased risk of hemorrhagic stroke (heterogeneity p <
      0.0001). Meta-analyses confirmed the associations and the heterogeneity across
      the 3 types of stroke. CONCLUSION: Classic risk factors for stroke have
      considerably different effects on the 3 main pathologic types of stroke.

PMID- 29321241
TI  - Evolution of the shut-off steps of vertebrate phototransduction.
AB  - Different isoforms of the genes involved in phototransduction are expressed in
      vertebrate rod and cone photoreceptors, providing a unique example of parallel
      evolution via gene duplication. In this study, we determine the molecular
      phylogeny of the proteins underlying the shut-off steps of phototransduction in
      the agnathan and jawed vertebrate lineages. For the G-protein receptor kinases
      (GRKs), the GRK1 and GRK7 divisions arose prior to the divergence of tunicates,
      with further expansion during the two rounds of whole-genome duplication (2R);
      subsequently, jawed and agnathan vertebrates retained different subsets of three
      isoforms of GRK. For the arrestins, gene expansion occurred during 2R.
      Importantly, both for GRKs and arrestins, the respective rod isoforms did not
      emerge until the second round of 2R, just prior to the separation of jawed and
      agnathan vertebrates. For the triplet of proteins mediating shut-off of the G
      protein transducin, RGS9 diverged from RGS11, probably at the second round of 2R,
      whereas Gbeta5 and R9AP appear not to have undergone 2R expansion. Overall, our
      analysis provides a description of the duplications and losses of
      phototransduction shut-off genes that occurred during the transition from a
      chordate with only cone-like photoreceptors to an ancestral vertebrate with both
      cone- and rod-like photoreceptors.

PMID- 29321242
TI  - Adhesion/growth-regulatory galectins tested in combination: evidence for
      formation of hybrids as heterodimers.
AB  - The delineation of the physiological significance of protein (lectin)-glycan
      recognition and the structural analysis of individual lectins have directed our
      attention to studying them in combination. In this report, we tested the
      hypothesis of hybrid formation by using binary mixtures of homodimeric galectin-1
      and -7 as well as a proteolytically truncated version of chimera-type galectin-3.
      Initial supportive evidence is provided by affinity chromatography using resin
      presented galectin-7. Intriguingly, the extent of cell binding by cross-linking
      of surface counter-receptor increased significantly for monomeric galectin-3 form
      by the presence of galectin-1 or -7. Pulsed-field gradient NMR (nuclear magnetic
      resonance) diffusion measurements on these galectin mixtures indicated formation
      of heterodimers as opposed to larger oligomers. 15N-1H heteronuclear single
      quantum coherence NMR spectroscopy and molecular dynamics simulations allowed us
      to delineate how different galectins interact in the heterodimer. The possibility
      of domain exchange between galectins introduces a new concept for understanding
      the spectrum of their functionality, particularly when these effector molecules
      are spatially and temporally co-expressed as found in vivo.

PMID- 29321240
TI  - Pigment-Dispersing Factor-expressing neurons convey circadian information in the
      honey bee brain.
AB  - Pigment-Dispersing Factor (PDF) is an important neuropeptide in the brain
      circadian network of Drosophila and other insects, but its role in bees in which
      the circadian clock influences complex behaviour is not well understood. We
      combined high-resolution neuroanatomical characterizations, quantification of PDF
      levels over the day and brain injections of synthetic PDF peptide to study the
      role of PDF in the honey bee Apis mellifera We show that PDF co-localizes with
      the clock protein Period (PER) in a cluster of laterally located neurons and that
      the widespread arborizations of these PER/PDF neurons are in close vicinity to
      other PER-positive cells (neurons and glia). PDF-immunostaining intensity
      oscillates in a diurnal and circadian manner with possible influences for age or
      worker task on synchrony of oscillations in different brain areas. Finally, PDF
      injection into the area between optic lobes and the central brain at the end of
      the subjective day produced a consistent trend of phase-delayed circadian rhythms
      in locomotor activity. Altogether, these results are consistent with the
      hypothesis that PDF is a neuromodulator that conveys circadian information from
      pacemaker cells to brain centres involved in diverse functions including
      locomotion, time memory and sun-compass orientation.

PMID- 29321239
TI  - Comparative genomic analysis of the 'pseudofungus' Hyphochytrium catenoides.
AB  - Eukaryotic microbes have three primary mechanisms for obtaining nutrients and
      energy: phagotrophy, photosynthesis and osmotrophy. Traits associated with the
      latter two functions arose independently multiple times in the eukaryotes. The
      Fungi successfully coupled osmotrophy with filamentous growth, and similar traits
      are also manifested in the Pseudofungi (oomycetes and hyphochytriomycetes). Both
      the Fungi and the Pseudofungi encompass a diversity of plant and animal
      parasites. Genome-sequencing efforts have focused on host-associated microbes
      (mutualistic symbionts or parasites), providing limited comparisons with free
      living relatives. Here we report the first draft genome sequence of a
      hyphochytriomycete 'pseudofungus'; Hyphochytrium catenoides Using phylogenomic
      approaches, we identify genes of recent viral ancestry, with related viral
      derived genes also present on the genomes of oomycetes, suggesting a complex
      history of viral coevolution and integration across the Pseudofungi. H.
      catenoides has a complex life cycle involving diverse filamentous structures and
      a flagellated zoospore with a single anterior tinselate flagellum. We use genome
      comparisons, drug sensitivity analysis and high-throughput culture arrays to
      investigate the ancestry of oomycete/pseudofungal characteristics, demonstrating
      that many of the genetic features associated with parasitic traits evolved
      specifically within the oomycete radiation. Comparative genomics also identified
      differences in the repertoire of genes associated with filamentous growth between
      the Fungi and the Pseudofungi, including differences in vesicle trafficking
      systems, cell-wall synthesis pathways and motor protein repertoire, demonstrating
      that unique cellular systems underpinned the convergent evolution of filamentous
      osmotrophic growth in these two eukaryotic groups.

PMID- 29321243
TI  - Adipose depot-specific effects of ileal interposition surgery in UCD-T2D rats:
      unexpected implications for obesity and diabetes.
AB  - Ileal interposition (IT) surgery delays the onset of diabetes in a rat model of
      type-2 diabetes (UCD-T2DM). Here, to gain a deeper understanding of the molecular
      events underlying the effects of IT surgery, we examined the changes in the
      proteome of four white adipose depots (retroperitoneal, mesenteric, inguinal, and
      epididymal) and plasma-free fatty acid profile in pre-diabetic rats 1.5 months
      following IT or sham surgery. The IT-mediated changes were exerted mainly in
      mesenteric fat and spanned from delayed adipocyte maturation to a neuroendocrine
      remodeling. Conversely, inguinal, retroperitoneal, and epididymal depots showed
      opposite trends consistent with increased adipocyte maturation and adipogenesis
      development prior to overt signs of diabetes, probably orchestrated by peroxisome
      proliferator-activated receptor gamma signaling and higher plasma n-6/n-3 free
      fatty acid ratios. The resulting scenario suggests a targeted use of surgical
      strategies that seek to delay or improve diabetes in order to manipulate adipose
      depot-specific responses to maximize the duration and beneficial effects of the
      surgery.

PMID- 29321245
TI  - Limited support for the X-linked grandmother hypothesis in pre-industrial
      Finland.
AB  - The level of kin help often depends on the degree of relatedness between a helper
      and the helped. In humans, grandmother help is known to increase the survival of
      grandchildren, though this benefit can differ between maternal grandmothers
      (MGMs) and paternal grandmothers (PGMs) and between grandsons and granddaughters.
      The X-linked grandmother hypothesis posits that differential X-chromosome
      relatedness between grandmothers and their grandchildren is a leading driver of
      differential grandchild survival between grandmother lineages and grandchild
      sexes. We tested this hypothesis using time-event models on a large,
      multigenerational dataset from pre-industrial Finland. We found that the presence
      of an MGM increases grandson survival more than PGM presence, and that
      granddaughter survival is higher than that of grandsons in the presence of a PGM.
      However, there was no support for the key prediction that the presence of PGMs
      improves granddaughter survival more than that of MGMs, diminishing the overall
      support for the hypothesis. Our results call for alternative explanations for
      differences in the effects of maternal and paternal kin to grandchild survival in
      humans.

PMID- 29321246
TI  - Unique perceptuomotor control of stone hammers in wild monkeys.
AB  - We analysed the patterns of coordination of striking movement and perceptuomotor
      control of stone hammers in wild bearded capuchin monkeys, Sapajus libidinosus as
      they cracked open palm nut using hammers of different mass, a habitual behaviour
      in our study population. We aimed to determine why these monkeys cannot produce
      conchoidally fractured flakes as do contemporary human knappers or as did
      prehistoric hominin knappers. We found that the monkeys altered their patterns of
      coordination of movement to accommodate changes in hammer mass. By altering their
      patterns of coordination, the monkeys kept the strike's amplitude and the
      hammer's velocity at impact constant with respect to hammer mass. In doing so,
      the hammer's kinetic energy at impact-which determines the propagation of a
      fracture/crack in a nut-varied across hammers of different mass. The monkeys did
      not control the hammer's kinetic energy at impact, the key parameter a perceiver
      actor should control while knapping stones. These findings support the hypothesis
      that the perceptuomotor control of stone hammers in wild bearded capuchin monkeys
      is inadequate to produce conchoidally fractured flakes by knapping stones, as do
      humans.

PMID- 29321244
TI  - Silencing carboxylesterase 1 in human THP-1 macrophages perturbs genes regulated
      by PPARgamma/RXR and RAR/RXR: down-regulation of CYP27A1-LXRalpha signaling.
AB  - Macrophage foam cells store excess cholesterol as cholesteryl esters, which need
      to be hydrolyzed for cholesterol efflux. We recently reported that silencing
      expression of carboxylesterase 1 (CES1) in human THP-1 macrophages [CES1KD (THP-1
      cells with CES1 expression knocked down) macrophages] reduced cholesterol uptake
      and decreased expression of CD36 and scavenger receptor-A in cells loaded with
      acetylated low-density lipoprotein (acLDL). Here, we report that CES1KD
      macrophages exhibit reduced transcription of cytochrome P45027A1 (CYP27A1) in
      nonloaded and acLDL-loaded cells. Moreover, levels of CYP27A1 protein and its
      enzymatic product, 27-hydroxycholesterol, were markedly reduced in CES1KD
      macrophages. Transcription of LXRalpha (liver X receptor alpha) and ABCA1 (ATP
      binding cassette transporter A1) was also decreased in acLDL-loaded CES1KD
      macrophages, suggesting reduced signaling through PPARgamma-CYP27A1-LXRalpha.
      Consistent with this, treatment of CES1KD macrophages with agonists for
      PPARgamma, RAR, and/or RAR/RXR partially restored transcription of CYP27A1 and
      LXRalpha, and repaired cholesterol influx. Conversely, treatment of control
      macrophages with antagonists for PPARgamma and/or RXR decreased transcription of
      CYP27A1 and LXRalpha Pharmacologic inhibition of CES1 in both wild-type THP-1
      cells and primary human macrophages also decreased CYP27A1 transcription. CES1
      silencing did not affect transcript levels of PPARgamma and RXR in acLDL-loaded
      macrophages, whereas it did reduce the catabolism of the endocannabinoid 2
      arachidonoylglycerol. Finally, the gene expression profile of CES1KD macrophages
      was similar to that of PPARgamma knockdown cells following acLDL exposures,
      further suggesting a mechanistic link between CES1 and PPARgamma. These results
      are consistent with a model in which abrogation of CES1 function attenuates the
      CYP27A1-LXRalpha-ABCA1 signaling axis by depleting endogenous ligands for the
      nuclear receptors PPARgamma, RAR, and/or RXR that regulate cholesterol
      homeostasis.

PMID- 29321248
TI  - Early-life maltreatment predicts adult stress response in a long-lived wild bird.
AB  - Persistent phenotypic changes due to early-life stressors are widely
      acknowledged, but their relevance for wild, free-living animals is poorly
      understood. We evaluated effects of two natural stressors experienced when young
      (maltreatment by adults and nutritional stress) on stress physiology in wild
      Nazca boobies (Sula granti) 6-8 years later, an exceptionally long interval for
      such studies. Maltreatment as a nestling, but not nutritional stress, was
      associated years later with depressed baseline corticosterone in females and
      elevated stress-induced corticosterone concentration [CORT] in males. These
      results provide rare evidence of long-term hormonal effects of natural early-life
      stress, which may be adaptive mechanisms for dealing with future stressors.

PMID- 29321249
TI  - Facing each other: mammal mothers and infants prefer the position favouring right
      hemisphere processing.
AB  - The right hemisphere plays a crucial role in social processing. Human mothers
      show a robust left cradling/holding bias providing greater right-hemispheric
      involvement in the exchange of social information between mother and infant.
      Here, we demonstrate that a similar bias is evident in face-to-face spatial
      interactions in marine and terrestrial non-primate mammals. Walruses and Indian
      flying foxes showed a significant population-level preference for the position
      which facilitates the use of the left visual field in both mother and infant.
      This behavioural lateralization may have emerged owing to benefits conferred by
      the enhanced right-hemispheric social processing providing the mother and infant
      an optimal perception of each other.

PMID- 29321247
TI  - Aberrant regulation of autophagy in mammalian diseases.
AB  - Autophagy is a major cellular metabolic pathway that facilitates degradation of a
      subset of long-lived proteins and cytoplasmic organelles in eukaryotic cells.
      This pathway plays a vital role in preserving the cellular homeostasis of the
      cells themselves, in addition to maintaining the normal physiological state of
      cell renewal. Many stressors, such as starvation, ischaemia and oxidative stress
      can induce autophagy. In addition to its physiological roles, autophagy also
      occurs in a wide variety of pathological processes, including tumour progression,
      metabolic disorders, and neurodegenerative and lung diseases. In recent years, a
      growing body of evidence has shown that autophagy also plays a key role in the
      development of mammalian diseases, a function that has garnered substantial
      attention and study. An in-depth understanding of the molecular role that
      autophagy plays in pathological settings is vital for both the diagnosis and
      treatment of mammalian diseases and will aid in the search for novel targets for
      therapeutic drug intervention. Here, we provide an integrated review of recent
      studies implicating autophagy dysfunction in the progression of mammalian
      disorders and summarize research suggesting that the molecular pathways involved
      in autophagy could serve as potential therapeutic targets.

PMID- 29321250
TI  - Myosin II-interacting guanine nucleotide exchange factor promotes bleb retraction
      via stimulating cortex reassembly at the bleb membrane.
AB  - Blebs are involved in various biological processes such as cell migration,
      cytokinesis, and apoptosis. While the expansion of blebs is largely an
      intracellular pressure-driven process, the retraction of blebs is believed to be
      driven by RhoA activation that leads to the reassembly of the actomyosin cortex
      at the bleb membrane. However, it is still poorly understood how RhoA is
      activated at the bleb membrane. Here, we provide evidence demonstrating that
      myosin II-interacting guanine nucleotide exchange factor (MYOGEF) is implicated
      in bleb retraction via stimulating RhoA activation and the reassembly of an
      actomyosin network at the bleb membrane during bleb retraction. Interaction of
      MYOGEF with ezrin, a well-known regulator of bleb retraction, is required for
      MYOGEF localization to retracting blebs. Notably, knockout of MYOGEF or ezrin not
      only disrupts RhoA activation at the bleb membrane, but also interferes with
      nonmuscle myosin II localization and activation, as well as actin polymerization
      in retracting blebs. Importantly, MYOGEF knockout slows down bleb retraction. We
      propose that ezrin interacts with MYOGEF and recruits it to retracting blebs,
      where MYOGEF activates RhoA and promotes the reassembly of the cortical
      actomyosin network at the bleb membrane, thus contributing to the regulation of
      bleb retraction.

PMID- 29321251
TI  - Control of septin filament flexibility and bundling by subunit composition and
      nucleotide interactions.
AB  - Septins self-assemble into heteromeric rods and filaments to act as scaffolds and
      modulate membrane properties. How cells tune the biophysical properties of septin
      filaments to control filament flexibility and length, and in turn the size,
      shape, and position of higher-order septin structures, is not well understood. We
      examined how rod composition and nucleotide availability influence physical
      properties of septins such as annealing, fragmentation, bundling, and bending. We
      found that septin complexes have symmetric termini, even when both Shs1 and Cdc11
      are coexpressed. The relative proportion of Cdc11/Shs1 septin complexes controls
      the biophysical properties of filaments and influences the rate of annealing,
      fragmentation, and filament flexibility. Additionally, the presence and apparent
      exchange of guanine nucleotide also alters filament length and bundling. An Shs1
      mutant that is predicted to alter nucleotide hydrolysis has altered filament
      length and dynamics in cells and impacts cell morphogenesis. These data show that
      modulating filament properties through rod composition and nucleotide binding can
      control formation of septin assemblies that have distinct physical properties and
      functions.

PMID- 29321252
TI  - Analysis of the thresholds for transcriptional activation by the yeast MAP
      kinases Fus3 and Kss1.
AB  - Signaling in the pheromone response pathway of budding yeast activates two
      distinct MAP kinases (MAPKs), Fus3 and Kss1. Either MAPK alone can mediate
      pheromone-induced transcription, but it has been unclear to what degree each one
      contributes to transcriptional output in wild-type cells. Here, we report that
      transcription reflects the ratio of active to inactive MAPK, and not simply the
      level of active MAPK. For Kss1 the majority of MAPK molecules must be converted
      to the active form, whereas for Fus3 only a small minority must be activated.
      These different activation thresholds reflect two opposing effects of each MAPK,
      in which the inactive forms inhibit transcription, whereas the active forms
      promote transcription. Moreover, negative feedback from Fus3 limits activation of
      Kss1 so that it does not meet its required threshold in wild-type cells but does
      so only when hyperactivated in cells lacking Fus3. The results suggest that the
      normal transcriptional response involves asymmetric contributions from the two
      MAPKs, in which pheromone signaling reduces the negative effect of Kss1 while
      increasing the positive effect of Fus3. These findings reveal new functional
      distinctions between these MAPKs, and help illuminate how inhibitory functions
      shape positive pathway outputs in both pheromone and filamentation pathways.

PMID- 29321254
TI  - Surgical Mortality and Race as a Risk Factor: A Compass, Not a Destination.

PMID- 29321253
TI  - Role of the Hof1-Cyk3 interaction in cleavage-furrow ingression and primary
      septum formation during yeast cytokinesis.
AB  - In Saccharomyces cerevisiae, it is well established that Hof1, Cyk3, and Inn1
      contribute to septum formation and cytokinesis. Because hof1? and cyk3? single
      mutants have relatively mild defects but hof1? cyk3? double mutants are nearly
      dead, it has been hypothesized that these proteins contribute to parallel
      pathways. However, there is also evidence that they interact physically. In this
      study, we examined this interaction and its functional significance in detail.
      Our data indicate that the interaction 1) is mediated by a direct binding of the
      Hof1 SH3 domain to a proline-rich motif in Cyk3; 2) occurs specifically at the
      time of cytokinesis but is independent of the (hyper)phosphorylation of both
      proteins that occurs at about the same time; 3) is dispensable for the normal
      localization of both proteins; 4) is essential for normal primary-septum
      formation and a normal rate of cleavage-furrow ingression; and 5) becomes
      critical for growth when either Inn1 or the type II myosin Myo1 (a key component
      of the contractile actomyosin ring) is absent. The similarity in phenotype
      between cyk3? mutants and mutants specifically lacking the Hof1-Cyk3 interaction
      suggests that the interaction is particularly important for Cyk3 function, but it
      may be important for Hof1 function as well.

PMID- 29321255
TI  - Multisite Emergency Department Inpatient Collaborative to Reduce Unnecessary
      Bronchiolitis Care.
AB  - BACKGROUND AND OBJECTIVES: There is high variation in the care of acute viral
      bronchiolitis. We sought to promote collaboration between emergency department
      (ED) and inpatient (IP) units with the goal of reducing unnecessary testing and
      treatment. METHODS: Multisite collaborative with improvement teams co-led by ED
      and IP physicians and a 1-year period of active participation. The intervention
      consisted of a multicomponent change package, regular webinars, and optional
      coaching. Data were collected by chart review for December 2014 through March
      2015 (baseline) and December 2015 to March 2016 (improvement period). Patients
      <24 months of age with a primary diagnosis of bronchiolitis and without ICU
      admission, prematurity, or chronic lung or heart disease were eligible for
      inclusion. Control charts were used to detect improvement. Achievable benchmarks
      of care were calculated for each measure. RESULTS: Thirty-five hospitals with
      5078 ED patients and 4389 IPs participated. Use of bronchodilators demonstrated
      special cause for the ED (mean centerline shift: 37.1%-24.5%, benchmark 5.8%) and
      IP (28.4%-17.7%, benchmark 9.1%). Project mean ED viral testing decreased from
      42.6% to 25.4% after revealing special cause with a 3.9% benchmark, whereas chest
      radiography (30.9%), antibiotic use (6.2%), and steroid use (7.6%) in the ED
      units did not change. IP steroid use decreased from 7.2% to 4.0% after special
      cause with 0.0% as the benchmark. Within-site ED and IP performance was modestly
      correlated. CONCLUSIONS: Collaboration between ED and IP units was associated
      with a decreased use of unnecessary tests and therapies in bronchiolitis; top
      performers used few unnecessary tests or treatments.

PMID- 29321256
TI  - Race, Preoperative Risk Factors, and Death After Surgery.
AB  - BACKGROUND AND OBJECTIVES: African American children are more than twice as
      likely to die after surgery compared with white children. In this study, we
      evaluated whether risk factors for death after surgery differ for African
      American and white children, and we also assessed whether race-specific risk
      stratification models perform better than non-race-specific models. METHODS: The
      National Surgical Quality Improvement Program Pediatric Participant Use Data File
      contains clinical data on operations performed on children at participating
      institutions in the United States. Variables predictive of death within 30 days
      of surgery were analyzed for differences in prevalence and strength of
      association with death for both African American and white children.
      Classification tree and network analysis were used. RESULTS: Network analyses
      revealed that the prevalence of preoperative risk factors associated with death
      after surgery was significantly higher for African American than for white
      children. In addition, many of the risk factors associated with death after
      surgery carried a higher risk when they occurred in African American children.
      Race-specific risk models provided high accuracy, with a specificity of 94% and a
      sensitivity of 83% for African American children and a specificity of 96% and a
      sensitivity of 77% for white children, and yet these 2 models were significantly
      different from each other. CONCLUSIONS: Race-specific models predict outcomes
      after surgery more accurately compared with non-race-specific models.
      Identification of race-specific modifiable risk factors may help reduce racial
      disparities in surgery outcome.

PMID- 29321257
TI  - The antimicrobial peptide SAAP-148 combats drug-resistant bacteria and biofilms.
AB  - Development of novel antimicrobial agents is a top priority in the fight against
      multidrug-resistant (MDR) and persistent bacteria. We developed a panel of
      synthetic antimicrobial and antibiofilm peptides (SAAPs) with enhanced
      antimicrobial activities compared to the parent peptide, human antimicrobial
      peptide LL-37. Our lead peptide SAAP-148 was more efficient in killing bacteria
      under physiological conditions in vitro than many known preclinical- and clinical
      phase antimicrobial peptides. SAAP-148 killed MDR pathogens without inducing
      resistance, prevented biofilm formation, and eliminated established biofilms and
      persister cells. A single 4-hour treatment with hypromellose ointment containing
      SAAP-148 completely eradicated acute and established, biofilm-associated
      infections with methicillin-resistant Staphylococcus aureus and MDR Acinetobacter
      baumannii from wounded ex vivo human skin and murine skin in vivo. Together,
      these data demonstrate that SAAP-148 is a promising drug candidate in the battle
      against antibiotic-resistant bacteria that pose a great threat to human health.

PMID- 29321259
TI  - Plasmacytoid dendritic cells promote systemic sclerosis with a key role for TLR8.
AB  - Systemic sclerosis (SSc) is a multisystem life-threatening fibrosing disorder
      that lacks effective treatment. The link between the inflammation observed in
      organs such as the skin and profibrotic mechanisms is not well understood. The
      plasmacytoid dendritic cell (pDC) is a key cell type mediating Toll-like receptor
      (TLR)-induced inflammation in autoimmune disease patients, including lupus and
      skin diseases with interface dermatitis. However, the role of pDCs in fibrosis is
      less clear. We show that pDCs infiltrate the skin of SSc patients and are
      chronically activated, leading to secretion of interferon-alpha (IFN-alpha) and
      CXCL4, which are both hallmarks of the disease. We demonstrate that the secretion
      of CXCL4 is under the control of phosphatidylinositol 3-kinase delta and is due
      to the aberrant presence of TLR8 on pDCs of SSc patients, which is not seen in
      healthy donors or in lupus pDCs, and that CXCL4 primarily acts by potentiating
      TLR8- but also TLR9-induced IFN production by pDCs. Depleting pDCs prevented
      disease in a mouse model of scleroderma and could revert fibrosis in mice with
      established disease. In contrast, the disease was exacerbated in mice transgenic
      for TLR8 with recruitment of pDCs to the fibrotic skin, whereas TLR7 only
      partially contributed to the inflammatory response, indicating that TLR8 is the
      key RNA-sensing TLR involved in the establishment of fibrosis. We conclude that
      the pDC is an essential cell type involved in the pathogenesis of SSc and its
      removal using depleting antibodies or attenuating pDC function could be a novel
      approach to treat SSc patients.

PMID- 29321260
TI  - Mechanobiologically optimized 3D titanium-mesh scaffolds enhance bone
      regeneration in critical segmental defects in sheep.
AB  - Three-dimensional (3D) titanium-mesh scaffolds offer many advantages over
      autologous bone grafting for the regeneration of challenging large segmental bone
      defects. Our study supports the hypothesis that endogenous bone defect
      regeneration can be promoted by mechanobiologically optimized Ti-mesh scaffolds.
      Using finite element techniques, two mechanically distinct Ti-mesh scaffolds were
      designed in a honeycomb-like configuration to minimize stress shielding while
      ensuring resistance against mechanical failure. Scaffold stiffness was altered
      through small changes in the strut diameter only. Honeycombs were aligned to form
      three differently oriented channels (axial, perpendicular, and tilted) to guide
      the bone regeneration process. The soft scaffold (0.84 GPa stiffness) and a 3.5
      fold stiffer scaffold (2.88 GPa) were tested in a critical size bone defect model
      in vivo in sheep. To verify that local scaffold stiffness could enhance healing,
      defects were stabilized with either a common locking compression plate that
      allowed dynamic loading of the 4-cm defect or a rigid custom-made plate that
      mechanically shielded the defect. Lower stress shielding led to earlier defect
      bridging, increased endochondral bone formation, and advanced bony regeneration
      of the critical size defect. This study demonstrates that mechanobiological
      optimization of 3D additive manufactured Ti-mesh scaffolds can enhance bone
      regeneration in a translational large animal study.

PMID- 29321261
TI  - A model-free method for measuring dimerization free energies of CLC-ec1 in lipid
      bilayers.
AB  - The thermodynamic reasons why membrane proteins form stable complexes inside the
      hydrophobic lipid bilayer remain poorly understood. This is largely because of a
      lack of membrane-protein systems amenable for equilibrium studies and a limited
      number of methods for measuring these reactions. Recently, we reported the
      equilibrium dimerization of the CLC-ec1 Cl-/H+ transporter in lipid bilayers
      (Chadda et al. 2016. eLife https://doi.org/10.7554/eLife.17438), which provided a
      new type of model system for studying protein association in membranes. The
      measurement was conducted using the subunit-capture approach, involving passive
      dilution of the protein in large multilamellar vesicles, followed by single
      molecule photobleaching analysis of the Poisson distribution describing protein
      encapsulation into extruded liposomes. To estimate the fraction of dimers (FDimer
      ) as a function of protein density, the photobleaching distributions for the
      nonreactive, ideal monomer and dimer species must be known so that random co
      capture probabilities can be accounted for. Previously, this was done by
      simulating the Poisson process of protein reconstitution into a known size
      distribution of liposomes composed of Escherichia coli polar lipids (EPLs). In
      the present study, we investigate the dependency of FDimer and DeltaG degrees  on
      the modeling through a comparison of different liposome size distributions (EPL
      versus 2:1 POPE/POPG). The results show that the estimated FDimer values are
      comparable, except at higher densities when liposomes become saturated with
      protein. We then develop empirical controls to directly measure the
      photobleaching distributions of the nonreactive monomer (CLC-ec1 I201W/I422W) and
      ideal dimer (WT CLC-ec1 cross-linked by glutaraldehyde or CLC-ec1 R230C/L249C
      cross-linked by a disulfide bond). The measured equilibrium constants do not
      depend on the correction method used, indicating the robustness of the subunit
      capture approach. This strategy therefore presents a model-free way to quantify
      protein dimerization in lipid bilayers, offering a simplified strategy in the
      ongoing effort to characterize equilibrium membrane-protein reactions in
      membranes.

PMID- 29321262
TI  - Nonsensing residues in S3-S4 linker's C terminus affect the voltage sensor set
      point in K+ channels.
AB  - Voltage sensitivity in ion channels is a function of highly conserved arginine
      residues in their voltage-sensing domains (VSDs), but this conservation does not
      explain the diversity in voltage dependence among different K+ channels. Here we
      study the non-voltage-sensing residues 353 to 361 in Shaker K+ channels and find
      that residues 358 and 361 strongly modulate the voltage dependence of the
      channel. We mutate these two residues into all possible remaining amino acids
      (AAs) and obtain Q-V and G-V curves. We introduced the nonconducting W434F
      mutation to record sensing currents in all mutants except L361R, which requires
      K+ depletion because it is affected by W434F. By fitting Q-Vs with a sequential
      three-state model for two voltage dependence-related parameters (V0, the voltage
      dependent transition from the resting to intermediate state and V1, from the
      latter to the active state) and G-Vs with a two-state model for the voltage
      dependence of the pore domain parameter (V1/2), Spearman's coefficients denoting
      variable relationships with hydrophobicity, available area, length, width, and
      volume of the AAs in 358 and 361 positions could be calculated. We find that
      mutations in residue 358 shift Q-Vs and G-Vs along the voltage axis by affecting
      V0, V1, and V1/2 according to the hydrophobicity of the AA. Mutations in residue
      361 also shift both curves, but V0 is affected by the hydrophobicity of the AA in
      position 361, whereas V1 and V1/2 are affected by size-related AA indices. Small
      to-tiny AAs have opposite effects on V1 and V1/2 in position 358 compared with
      361. We hypothesize possible coordination points in the protein that residues 358
      and 361 would temporarily and differently interact with in an intermediate state
      of VSD activation. Our data contribute to the accumulating knowledge of voltage
      dependent ion channel activation by adding functional information about the
      effects of so-called non-voltage-sensing residues on VSD dynamics.

PMID- 29321263
TI  - Estimating kinetic mechanisms with prior knowledge II: Behavioral constraints and
      numerical tests.
AB  - Kinetic mechanisms predict how ion channels and other proteins function at the
      molecular and cellular levels. Ideally, a kinetic model should explain new data
      but also be consistent with existing knowledge. In this two-part study, we
      present a mathematical and computational formalism that can be used to enforce
      prior knowledge into kinetic models using constraints. Here, we focus on
      constraints that quantify the behavior of the model under certain conditions, and
      on constraints that enforce arbitrary parameter relationships. The penalty-based
      optimization mechanism described here can be used to enforce virtually any model
      property or behavior, including those that cannot be easily expressed through
      mathematical relationships. Examples include maximum open probability, use
      dependent availability, and nonlinear parameter relationships. We use a simple
      kinetic mechanism to test multiple sets of constraints that implement linear
      parameter relationships and arbitrary model properties and behaviors, and we
      provide numerical examples. This work complements and extends the companion
      article, where we show how to enforce explicit linear parameter relationships. By
      incorporating more knowledge into the parameter estimation procedure, it is
      possible to obtain more realistic and robust models with greater predictive
      power.

PMID- 29321258
TI  - Functional variants in the LRRK2 gene confer shared effects on risk for Crohn's
      disease and Parkinson's disease.
AB  - Crohn's disease (CD), a form of inflammatory bowel disease, has a higher
      prevalence in Ashkenazi Jewish than in non-Jewish European populations. To define
      the role of nonsynonymous mutations, we performed exome sequencing of Ashkenazi
      Jewish patients with CD, followed by array-based genotyping and association
      analysis in 2066 CD cases and 3633 healthy controls. We detected association
      signals in the LRRK2 gene that conferred risk for CD (N2081D variant, P = 9.5 *
      10-10) or protection from CD (N551K variant, tagging R1398H-associated haplotype,
      P = 3.3 * 10-8). These variants affected CD age of onset, disease location, LRRK2
      activity, and autophagy. Bayesian network analysis of CD patient intestinal
      tissue further implicated LRRK2 in CD pathogenesis. Analysis of the extended
      LRRK2 locus in 24,570 CD cases, patients with Parkinson's disease (PD), and
      healthy controls revealed extensive pleiotropy, with shared genetic effects
      between CD and PD in both Ashkenazi Jewish and non-Jewish cohorts. The LRRK2
      N2081D CD risk allele is located in the same kinase domain as G2019S, a mutation
      that is the major genetic cause of familial and sporadic PD. Like the G2019S
      mutation, the N2081D variant was associated with increased kinase activity,
      whereas neither N551K nor R1398H variants on the protective haplotype altered
      kinase activity. We also confirmed that R1398H, but not N551K, increased
      guanosine triphosphate binding and hydrolyzing enzyme (GTPase) activity, thereby
      deactivating LRRK2. The presence of shared LRRK2 alleles in CD and PD provides
      refined insight into disease mechanisms and may have major implications for the
      treatment of these two seemingly unrelated diseases.

PMID- 29321264
TI  - Estimating kinetic mechanisms with prior knowledge I: Linear parameter
      constraints.
AB  - To understand how ion channels and other proteins function at the molecular and
      cellular levels, one must decrypt their kinetic mechanisms. Sophisticated
      algorithms have been developed that can be used to extract kinetic parameters
      from a variety of experimental data types. However, formulating models that not
      only explain new data, but are also consistent with existing knowledge, remains a
      challenge. Here, we present a two-part study describing a mathematical and
      computational formalism that can be used to enforce prior knowledge into the
      model using constraints. In this first part, we focus on constraints that enforce
      explicit linear relationships involving rate constants or other model parameters.
      We develop a simple, linear algebra-based transformation that can be applied to
      enforce many types of model properties and assumptions, such as microscopic
      reversibility, allosteric gating, and equality and inequality parameter
      relationships. This transformation converts the set of linearly interdependent
      model parameters into a reduced set of independent parameters, which can be
      passed to an automated search engine for model optimization. In the companion
      article, we introduce a complementary method that can be used to enforce
      arbitrary parameter relationships and any constraints that quantify the behavior
      of the model under certain conditions. The procedures described in this study
      can, in principle, be coupled to any of the existing methods for solving
      molecular kinetics for ion channels or other proteins. These concepts can be used
      not only to enforce existing knowledge but also to formulate and test new
      hypotheses.

PMID- 29321266
TI  - Optimization-based synthesis of stochastic biocircuits with statistical
      specifications.
AB  - Model-guided design has become a standard approach to engineering biomolecular
      circuits in synthetic biology. However, the stochastic nature of biomolecular
      reactions is often overlooked in the design process. As a result, cell-cell
      heterogeneity causes unexpected deviation of biocircuit behaviours from model
      predictions and requires additional iterations of design-build-test cycles. To
      enhance the design process of stochastic biocircuits, this paper presents a
      computational framework to systematically specify the level of intrinsic noise
      using well-defined metrics of statistics and design highly heterogeneous
      biocircuits based on the specifications. Specifically, we use descriptive
      statistics of population distributions as an intuitive specification language of
      stochastic biocircuits and develop an optimization-based computational tool that
      explores parameter configurations satisfying design requirements. Sensitivity
      analysis methods are also performed to ensure the robustness of a biocircuit
      design against extrinsic perturbations. These design tools are formulated with
      convex optimization programs to enable rigorous and efficient quantification of
      the statistics. We demonstrate these features by designing a stochastic negative
      feedback biocircuit that satisfies multiple statistical constraints and perform
      an in-depth study of noise propagation and regulation in negative feedback
      pathways.

PMID- 29321265
TI  - Contribution of low-temperature single-molecule techniques to structural issues
      of pigment-protein complexes from photosynthetic purple bacteria.
AB  - As the electronic energies of the chromophores in a pigment-protein complex are
      imposed by the geometrical structure of the protein, this allows the spectral
      information obtained to be compared with predictions derived from structural
      models. Thereby, the single-molecule approach is particularly suited for the
      elucidation of specific, distinctive spectral features that are key for a
      particular model structure, and that would not be observable in ensemble-averaged
      spectra due to the heterogeneity of the biological objects. In this concise
      review, we illustrate with the example of the light-harvesting complexes from
      photosynthetic purple bacteria how results from low-temperature single-molecule
      spectroscopy can be used to discriminate between different structural models.
      Thereby the low-temperature approach provides two advantages: (i) owing to the
      negligible photobleaching, very long observation times become possible, and more
      importantly, (ii) at cryogenic temperatures, vibrational degrees of freedom are
      frozen out, leading to sharper spectral features and in turn to better resolved
      spectra.

PMID- 29321267
TI  - Extreme call amplitude from near-field acoustic wave coupling in the stridulating
      water insect Micronecta scholtzi (Micronectinae).
AB  - Underwater acoustic transducers, particularly at low frequencies, are beset by
      problems of scale and inefficiency due to the large wavelengths of sound in
      water. In insect mating calls, a high call volume is usually desirable,
      increasing the range of signal transmission and providing a form of advertisement
      of the signaller's quality to a potential mate; however, the strength of the call
      is constrained by body size and by the need to avoid predators who may be
      listening in. Male crickets and water boatmen avoid some of the limitations of
      body size by exploiting resonant structures, which produce sharply tuned species
      specific songs, but call frequency and volume remain linked to body size.
      Recently, the water boatman Micronecta scholtzi was found to circumvent this
      rule, producing a louder mating call than that of similar, but much larger,
      Corixa The resonant structure in Corixidae and Micronectinae is believed to be
      the trapped air reserves around the insect as it dives, driven by a stridulatory
      apparatus. However, the method by which energy is transferred from the striated
      area to the bubble is unknown. Here, we present modelling of a system of near
      field coupling of acoustic sources to bubbles showing an exponential increase in
      sound power gain with decreasing distance that provides a simple solution to the
      stimulus of the air bubbles in Corixidae and Micronectinae and explains the
      discrepancy of M. scholtzi's extreme call volume. The findings suggest a possible
      route to engineered systems using near-field coupling to overcome size
      constraints in low-frequency (less than 500 Hz) underwater transducers, where the
      input efficiency of a piezoelectric device can be coupled through the
      hydrodynamic field to the high radiative efficiency of a near-ideal monopole
      emitter.

PMID- 29321268
TI  - Computational techniques for ECG analysis and interpretation in light of their
      contribution to medical advances.
AB  - Widely developed for clinical screening, electrocardiogram (ECG) recordings
      capture the cardiac electrical activity from the body surface. ECG analysis can
      therefore be a crucial first step to help diagnose, understand and predict
      cardiovascular disorders responsible for 30% of deaths worldwide. Computational
      techniques, and more specifically machine learning techniques and computational
      modelling are powerful tools for classification, clustering and simulation, and
      they have recently been applied to address the analysis of medical data,
      especially ECG data. This review describes the computational methods in use for
      ECG analysis, with a focus on machine learning and 3D computer simulations, as
      well as their accuracy, clinical implications and contributions to medical
      advances. The first section focuses on heartbeat classification and the
      techniques developed to extract and classify abnormal from regular beats. The
      second section focuses on patient diagnosis from whole recordings, applied to
      different diseases. The third section presents real-time diagnosis and
      applications to wearable devices. The fourth section highlights the recent field
      of personalized ECG computer simulations and their interpretation. Finally, the
      discussion section outlines the challenges of ECG analysis and provides a
      critical assessment of the methods presented. The computational methods reported
      in this review are a strong asset for medical discoveries and their translation
      to the clinical world may lead to promising advances.

PMID- 29321269
TI  - Adding levels of complexity enhances robustness and evolvability in a multilevel
      genotype-phenotype map.
AB  - Robustness and evolvability are the main properties that account for the
      stability and accessibility of phenotypes. They have been studied in a number of
      computational genotype-phenotype maps. In this paper, we study a metabolic
      genotype-phenotype map defined in toyLIFE, a multilevel computational model that
      represents a simplified cellular biology. toyLIFE includes several levels of
      phenotypic expression, from proteins to regulatory networks to metabolism. Our
      results show that toyLIFE shares many similarities with other seemingly unrelated
      computational genotype-phenotype maps. Thus, toyLIFE shows a high degeneracy in
      the mapping from genotypes to phenotypes, as well as a highly skewed distribution
      of phenotypic abundances. The neutral networks associated with abundant
      phenotypes are highly navigable, and common phenotypes are close to each other in
      genotype space. All of these properties are remarkable, as toyLIFE is built on a
      version of the HP protein-folding model that is neither robust nor evolvable:
      phenotypes cannot be mutually accessed through point mutations. In addition, both
      robustness and evolvability increase with the number of genes in a genotype.
      Therefore, our results suggest that adding levels of complexity to the mapping of
      genotypes to phenotypes and increasing genome size enhances both these
      properties.

PMID- 29321270
TI  - Phenotypes can be robust and evolvable if mutations have non-local effects on
      sequence constraints.
AB  - The mapping between biological genotypes and phenotypes plays an important role
      in evolution, and understanding the properties of this mapping is crucial to
      determine the outcome of evolutionary processes. One of the most striking
      properties observed in several genotype-phenotype (GP) maps is the positive
      correlation between the robustness and evolvability of phenotypes. This implies
      that a phenotype can be strongly robust against mutations and at the same time
      evolvable to a diverse range of alternative phenotypes. Here, we examine the
      causes for this positive correlation by introducing two analytically tractable GP
      map models that follow the principles of real biological GP maps. The first model
      is based on gene-like GP maps, reflecting the way in which genetic sequences are
      organized into protein-coding genes, and the second one is based on the GP map of
      RNA secondary structure. For both models, we find that a positive correlation
      between phenotype robustness and evolvability only emerges if mutations at one
      sequence position can have non-local effects on the sequence constraints at
      another position. This highlights that non-local effects of mutations are closely
      related to the coexistence of robustness and evolvability in phenotypes, and are
      likely to be an important feature of many biological GP maps.

PMID- 29321272
TI  - Slapped with a fine or a slap on the wrist? Enforcing tobacco licensing
      legislation.

PMID- 29321271
TI  - Incremental distribution of strontium and zinc in great ape and fossil hominin
      cementum using synchrotron X-ray fluorescence mapping.
AB  - Cementum and the incremental markings it contains have been widely studied as a
      means of ageing animals and retrieving information about diet and nutrition. The
      distribution of trace elements in great ape and fossil hominin cementum has not
      been studied previously. Synchrotron X-ray fluorescence (SXRF) enables rapid
      scanning of large tissue areas with high resolution of elemental distributions.
      First, we used SXRF to map calcium, phosphorus, strontium and zinc distributions
      in great ape dentine and cementum. At higher resolution, we compared zinc and
      strontium distributions in cellular and acellular cementum in regions where clear
      incremental markings were expressed. We then mapped trace element distributions
      in fossil hominin dentine and cementum from the 1.55-1.65 million year old site
      of Koobi Fora, Kenya. Zinc, in particular, is a precise marker of cementum
      increments in great apes, and is retained in fossil hominin cementum, but does
      not correspond well with the more diffuse fluctuations observed in strontium
      distribution. Cementum is unusual among mineralized tissues in retaining so much
      zinc. This is known to reduce the acid solubility of hydroxyapatite and so may
      confer resistance to resorption by osteoclasts in the dynamic remodelling
      environment of the periodontal ligament and alveolar bone.

PMID- 29321273
TI  - How tobacco companies in the United Kingdom prepared for, and responded to,
      standardised packaging of cigarettes and rolling tobacco.
AB  - INTRODUCTION: As a result of the Standardised Packaging of Tobacco Products
      Regulations and Tobacco Products Directive, all packs of cigarettes (factory-made
      and hand-rolled) in the UK must be drab brown, display pictorial warnings on the
      principal display areas and contain no less than 20 cigarettes or 30 g of
      tobacco. The legislation was phased in between May 2016 and May 2017. Our
      objective was to monitor pack, brand and product changes preimplementation and
      postimplementation. METHODS: Our surveillance of the cigarette market involved a
      review of the trade press, a monthly monitor of online supermarkets and regular
      visits to stores, from May 2015 to June 2017. RESULTS: Before standardised
      packaging there were changes to the pack graphics (eg, redesigned packs and
      limited editions) and pack structure (eg, resealable inner foil) and the issue of
      a number of reusable tins. After standardised packaging, changes included newer
      cigarette pack sizes for some brand variants (eg, 23 and 24 packs). Changes to
      the branding prestandardised packaging included brand extensions, and
      poststandardised packaging included brand and/or variant name change, often with
      the inclusion of colour descriptors and brand migrations. Product changes
      prestandardised packaging included the introduction of novel filters (eg, filters
      with two flavour-changing capsules, tube filters, firmer filters and filters with
      granular additives). There was non-compliance with the legislation, with slim
      packs, which are not permitted, on sale after standardised packaging was
      implemented. CONCLUSIONS: Our findings highlight the need to monitor developments
      in markets introducing standardised packaging and have policy implications for
      countries considering this measure.

PMID- 29321274
TI  - IRF1 Is a Transcriptional Regulator of ZBP1 Promoting NLRP3 Inflammasome
      Activation and Cell Death during Influenza Virus Infection.
AB  - Innate immune sensing of influenza A virus (IAV) induces activation of various
      immune effector mechanisms, including the nucleotide and oligomerization domain,
      leucine-rich repeat-containing protein family, pyrin domain containing 3 (NLRP3)
      inflammasome and programmed cell death pathways. Although type I IFNs are
      identified as key mediators of inflammatory and cell death responses during IAV
      infection, the involvement of various IFN-regulated effectors in facilitating
      these responses are less studied. In this study, we demonstrate the role of IFN
      regulatory factor (IRF)1 in promoting NLRP3 inflammasome activation and cell
      death during IAV infection. Both inflammasome-dependent responses and induction
      of apoptosis and necroptosis are reduced in cells lacking IRF1 infected with IAV.
      The observed reduction in inflammasome activation and cell death in IRF1
      deficient cells during IAV infection correlates with reduced levels of Z-DNA
      binding protein 1 (ZBP1), a key molecule mediating IAV-induced inflammatory and
      cell death responses. We further demonstrate IRF1 as a transcriptional regulator
      of ZBP1. Overall, our study identified IRF1 as an upstream regulator of NLRP3
      inflammasome and cell death during IAV infection and further highlights the
      complex and multilayered regulation of key molecules controlling inflammatory
      response and cell fate decisions during infections.

PMID- 29321275
TI  - CD40 Mediates Maturation of Thymic Dendritic Cells Driven by Self-Reactive CD4+
      Thymocytes and Supports Development of Natural Regulatory T Cells.
AB  - Thymic dendritic cells (tDCs) play an important role in central tolerance by
      eliminating self-reactive thymocytes or differentiating them to regulatory T
      (Treg) cells. However, the molecular and cellular mechanisms underlying these
      functions are not completely understood. We found that mouse tDCs undergo
      maturation following cognate interaction with self-reactive CD4+ thymocytes and
      that this maturation is dependent on CD40 signaling. Ablation of CD40 expression
      in tDCs resulted in a significant reduction in the number of Treg cells in
      association with a significant reduction in the number of mature tDCs. In
      addition, CD40-deficient DCs failed to fully mature upon cognate interaction with
      CD4+ thymocytes in vitro and failed to differentiate them into Treg cells to a
      sufficient number. These findings suggest that tDCs mature and potentiate Treg
      cell development in feedback response to self-reactive CD4+ thymocytes.

PMID- 29321276
TI  - IFN Regulatory Factor 3 Balances Th1 and T Follicular Helper Immunity during
      Nonlethal Blood-Stage Plasmodium Infection.
AB  - Differentiation of CD4+ Th cells is critical for immunity to malaria. Several
      innate immune signaling pathways have been implicated in the detection of blood
      stage Plasmodium parasites, yet their influence over Th cell immunity remains
      unclear. In this study, we used Plasmodium-reactive TCR transgenic CD4+ T cells,
      termed PbTII cells, during nonlethal P. chabaudi chabaudi AS and P. yoelii 17XNL
      infection in mice, to examine Th cell development in vivo. We found no role for
      caspase1/11, stimulator of IFN genes, or mitochondrial antiviral-signaling
      protein, and only modest roles for MyD88 and TRIF-dependent signaling in
      controlling PbTII cell expansion. In contrast, IFN regulatory factor 3 (IRF3) was
      important for supporting PbTII expansion, promoting Th1 over T follicular helper
      (Tfh) differentiation, and controlling parasites during the first week of
      infection. IRF3 was not required for early priming by conventional dendritic
      cells, but was essential for promoting CXCL9 and MHC class II expression by
      inflammatory monocytes that supported PbTII responses in the spleen. Thereafter,
      IRF3-deficiency boosted Tfh responses, germinal center B cell and memory B cell
      development, parasite-specific Ab production, and resolution of infection. We
      also noted a B cell-intrinsic role for IRF3 in regulating humoral immune
      responses. Thus, we revealed roles for IRF3 in balancing Th1- and Tfh-dependent
      immunity during nonlethal infection with blood-stage Plasmodium parasites.

PMID- 29321277
TI  - Intrathymic Deletion of IL-7 Reveals a Contribution of the Bone Marrow to Thymic
      Rebound Induced by Androgen Blockade.
AB  - Despite the well-documented effect of castration in thymic regeneration, the
      singular contribution of the bone marrow (BM) versus the thymus to this process
      remains unclear. The chief role of IL-7 in pre- and intrathymic stages of T
      lymphopoiesis led us to investigate the impact of disrupting this cytokine during
      thymic rebound induced by androgen blockade. We found that castration promoted
      thymopoiesis in young and aged wild-type mice. In contrast, only young germline
      IL-7-deficient (Il7-/- ) mice consistently augmented thymopoiesis after
      castration. The increase in T cell production was accompanied by the expansion of
      the sparse medullary thymic epithelial cell and the peripheral T cell compartment
      in young Il7-/- mice. In contrast to young Il7-/- and wild-type mice, the poor
      thymic response of aged Il7-/- mice after castration was associated with a defect
      in the expansion of BM hematopoietic progenitors. These findings suggest that BM
      derived T cell precursors contribute to thymic rebound driven by androgen
      blockade. To assess the role of IL-7 within the thymus, we generated mice with
      conditional deletion of IL-7 (Il7 conditional knockout [cKO]) in thymic
      epithelial cells. As expected, Il7cKO mice presented a profound defect in T cell
      development while maintaining an intact BM hematopoietic compartment across life.
      Unlike Il7-/- mice, castration promoted the expansion of BM precursors and
      enhanced thymic activity in Il7cKO mice independently of age. Our findings
      suggest that the mobilization of BM precursors acts as a prime catalyst of
      castration-driven thymopoiesis.

PMID- 29321278
TI  - Spemann-Mangold Grafts.
AB  - In 1924, Hans Spemann and Hilde Mangold (nee Proscholdt) published their famous
      work describing the transplantation of dorsal blastopore lip of one newt gastrula
      embryo onto the ventral side of a host embryo at the same stage. They performed
      these grafts using two newt species with different pigmentation (Triturus
      taeniatus and Triturus cristatus) to follow the fate of the grafted tissue. These
      experiments resulted in the development of conjoined twins attached through their
      belly. Because of the difference in embryo pigmentation between the two Triturus
      species, they determined that the bulk of the secondary embryo arose from the
      host embryo while the grafted tissue per se gave increase to the notochord and a
      few somitic cells. This meant that the dorsal blastopore lip was able to organize
      an almost complete embryo out of ventral tissue. The dorsal blastopore lip is now
      called the Spemann-Mangold organizer. Here, we describe a simple yet efficient
      protocol to perform these grafts using the anuran Xenopus laevis.

PMID- 29321279
TI  - Whole-Mount Immunofluorescence for Visualizing Endogenous Protein and Injected
      RNA in Xenopus Oocytes.
AB  - Asymmetric distribution of mRNA and protein is a hallmark of cell polarity in
      many systems. The Xenopus laevis oocyte provides many technical advantages to
      studying such polarity. Thousands of oocytes at different stages of maturity can
      be harvested from a single ovary and, owing to their relatively large size, even
      the youngest oocytes can be manually microinjected. Microinjection of
      fluorescently labeled RNA combined with immunofluorescence of endogenous proteins
      can provide insight into the cytoplasmic interactions contributing to polarity.
      Here, we present an updated method to image endogenous protein and microinjected
      RNA in X. laevis oocytes.

PMID- 29321280
TI  - Analysis of Mitotic Checkpoint Function in Xenopus Egg Extracts.
AB  - Accurate sister chromatid segregation is pivotal in the faithful transmission of
      genetic information during each cell division. To ensure accurate segregation,
      eukaryotic organisms have evolved a "mitotic (or spindle assembly) checkpoint" to
      prevent premature advance to anaphase before successful attachment of every
      chromosome to the microtubules of the mitotic spindle. An unattached kinetochore
      generates a diffusible signal that inhibits ubiquitination of substrates such as
      cyclin B and securins. This protocol presents an in vitro assay for studying the
      mitotic checkpoint using Xenopus laevis egg extracts. Meiotic spindles assembled
      around nuclei added to egg extracts are synchronized at metaphase by an
      endogenous activity known as cytostatic factor (CSF). Normally, the mitotic
      checkpoint results in continued metaphase arrest following inactivation of CSF
      activity (by addition of calcium) and disassembly of spindle microtubules (with a
      microtubule inhibitor such as nocodazole). Simple DAPI staining for chromatin
      structure or biochemical analysis of Cdc2/cyclin B (cyclin-dependent kinase)
      histone H1 kinase activity can be used to evaluate the stages of the cell cycle
      and the status of the mitotic checkpoint. This cell-free system derived from
      Xenopus eggs has been successfully used to unravel the mechanisms of mitosis, and
      it provides a distinct advantage over cell-based studies in which perturbing
      kinetochore functions often results in lethality.

PMID- 29321281
TI  - Dissecting Protein Complexes in Branching Microtubule Nucleation Using Meiotic
      Xenopus Egg Extracts.
AB  - The mitotic spindle is the microtubule-based apparatus that reliably segregates
      chromosomes during cell division. Recently, it was discovered that microtubules
      originate within the mitotic spindle by nucleating off of existing spindle
      microtubules. This mechanism, termed branching microtubule nucleation, allows the
      efficient amplification of microtubules while preserving their original polarity
      as required in the spindle. Three molecular players are known to be involved in
      this process, namely, the protein TPX2, the protein complex augmin, and the gamma
      tubulin ring complex; however, little is known about the assembly of the protein
      complexes. Here, we use the eight-subunit augmin complex as an example of how to
      dissect the function and assembly of a protein complex using meiotic Xenopus egg
      extracts. Specifically, immunodepletion combined with total internal reflection
      fluorescence (TIRF) microscopy is used to identify the role of the protein
      complex. In parallel, immunoprecipitation (IP) and tandem mass spectrometry
      (MS/MS) are used to infer how it is assembled. This approach can be applied to
      investigate the assembly of other multisubunit protein complexes that function in
      branching microtubule nucleation and mitotic spindle assembly.

PMID- 29321282
TI  - Nucleus Assembly and Import in Xenopus laevis Egg Extract.
AB  - Xenopus egg extract represents a powerful cell-free biochemical tool for studying
      organelle assembly and function. Large quantities of cytoplasm can be isolated,
      and biochemical manipulation of extract composition and cell cycle state is
      relatively straightforward. In this protocol, we describe the reconstitution of
      nuclear assembly by adding a chromatin source to interphasic X. laevis egg
      extract. Intact nuclei assemble within 30-45 min of initiating the reaction,
      followed by nuclear growth. We also describe methods for imaging and quantifying
      nuclear import kinetics. Recombinant proteins or small molecules of interest can
      be added to the extract before or after nuclear assembly, and immunodepletion
      allows for removal of specific proteins from the extract. This approach will
      continue to inform mechanisms of nuclear assembly, nuclear pore complex assembly
      and function, nucleocytoplasmic transport, DNA replication, nuclear envelope
      breakdown, and nuclear size and shape regulation.

PMID- 29321283
TI  - Cranial Neural Crest Explants.
AB  - The cranial neural crest (CNC) explant assay was originally designed to assess
      the basic requirements for CNC migration in vitro. This protocol describes the
      key parameters of CNC explants in Xenopus laevis, with a focus on how to
      extirpate CNC cells and assay their migration in vitro. The protocol can be
      adapted according to the needs of the experimenter, some examples of which are
      discussed here.

PMID- 29321284
TI  - Microinjection of Xenopus Oocytes.
AB  - Microinjection of Xenopus oocytes has proven to be a valuable tool in a broad
      array of studies that require expression of DNA or RNA into functional protein.
      These studies are diverse and range from expression cloning to receptor-ligand
      interaction to nuclear programming. Oocytes offer a number of advantages for such
      studies, including their large size (~1.2 mm in diameter), capacity for
      translation, and enormous nucleus (0.3-0.4 mm). They are cost effective, easily
      manipulated, and can be injected in large numbers in a short time period. Oocytes
      have a large maternal stockpile of all the essential components for transcription
      and translation. Consequently, the investigator needs only to introduce by
      microinjection the specific DNA or RNA of interest for synthesis. Oocytes
      translate virtually any exogenous RNA regardless of source, and the translated
      proteins are folded, modified, and transported to the correct cellular locations.
      Here we present procedures for the efficient microinjection of oocytes and their
      subsequent care.

PMID- 29321285
TI  - Cranial Neural Crest Transplants.
AB  - The transplantation of cranial neural crest (CNC) expressing green fluorescent
      protein (GFP) in Xenopus laevis has allowed researchers not only to assess CNC
      migration in vivo but also to address many other experimental questions. Coupled
      with loss- or gain-of-function experiments, this technique can be used to
      characterize the function of specific genes during CNC migration and
      differentiation. Although targeted injection can also be used to assess gene
      function during CNC migration, CNC transplantation allows one to answer specific
      questions, such as whether a gene's function is tissue autonomous, cell
      autonomous, or exerted in the tissues surrounding the CNC. Here we describe a
      protocol for performing simple CNC grafts.

PMID- 29321286
TI  - Oocyte Host-Transfer and Maternal mRNA Depletion Experiments in Xenopus.
AB  - This protocol details the oocyte host-transfer method in Xenopus, using
      transplantation by intraperitoneal injection. This approach is suitable for the
      overexpression of mRNAs and for the use of antisense oligonucleotides to deplete
      maternal mRNAs, which are not replaced until zygotic genome activation in the mid
      blastula transition. Xenopus oocyte host-transfer can also be used for highly
      efficient mutagenesis in the F0 generation by prefertilization injection of
      genome editing reagents.

PMID- 29321287
TI  - Isolation of Xenopus Oocytes.
AB  - Xenopus oocytes and oocyte extracts are the starting material for a variety of
      experimental approaches. Oocytes are obtained by surgical removal of the ovary
      from anesthetized females. Although oocytes may be used while they remain within
      their ovarian follicle, it is more practical to work with defolliculated oocytes.
      Defolliculation can be performed either manually or enzymatically. Here we
      present a protocol for the isolation and separation of Xenopus oocytes at various
      developmental stages, and guidelines for maintaining oocytes in culture.

PMID- 29321288
TI  - Einsteck Transplants.
AB  - Einsteck procedure refers to a method whereby the experimenter inserts material
      into the blastocoel cavity of an early amphibian embryo. This procedure is
      simpler to perform than other types of grafts, such as Spemann-Mangold, and with
      practice yields a sizable amount of data suitable for statistical analysis. This
      protocol for Einsteck transplantation in Xenopus describes the insertion of the
      gastrula-stage blastopore lip into the blastocoel cavity of a host embryo.

PMID- 29321289
TI  - Connecting to ecology: a challenge for comparative physiologists? Response to
      'Oxygen- and capacity-limited thermal tolerance: blurring ecology and
      physiology'.

PMID- 29321290
TI  - Early-career researchers: an interview with Brooke Flammang.
AB  - Brooke Flammang is an Assistant Professor at the New Jersey Institute of
      Technology, where she investigates how organisms interact with their environment
      and how these interactions drive the evolutionary selection of morphology and
      function. She received her Bachelor's degree in Marine Biology from Fairleigh
      Dickinson University before moving to Moss Landing Marine Laboratories for her
      Master's degree and completing her PhD with George Lauder at Harvard University
      in 2010. She was awarded the Dorothy H. Skinner award in 2013 and the Carl Gans
      award in 2017 by the Society for Integrative and Comparative Biology.

PMID- 29321291
TI  - Oxygen- and capacity-limited thermal tolerance: blurring ecology and physiology.

PMID- 29321292
TI  - Atlantic bluefin tuna spawn at suboptimal temperatures for their offspring.
AB  - Life-history traits such as spawning migrations and timing of reproduction are
      adaptations to specific environmental constraints and seasonal cycles in many
      organisms' annual routines. In this study we analyse how offspring fitness
      constrains spawning phenology in a large migratory apex predator, the Atlantic
      bluefin tuna. The reproductive schedule of Atlantic bluefin tuna varies between
      spawning sites, suggesting plasticity to local environmental conditions.
      Generally, temperature is considered to be the main constraint on tuna spawning
      phenology. We combine evidence from long-term field data, temperature-controlled
      rearing experiments on eggs and larvae, and a model of egg fitness, and show that
      Atlantic bluefin tuna do not spawn to optimize egg and larval temperature
      exposure. The timing of spawning leads to temperature exposure considerably lower
      than optimal at all spawning grounds across the Atlantic Ocean. The early
      spawning is constrained by thermal inhibition of egg hatching and larval growth
      rates, but some other factors must prevent later spawning. Matching offspring
      with ocean productivity and the prey peak might be an important driver for
      bluefin tuna spawning phenology. This finding is important for predictions of
      reproductive timing in future climate warming scenarios for bluefin tuna.

PMID- 29321293
TI  - Individual variation in reproductive behaviour is linked to temporal
      heterogeneity in predation risk.
AB  - Variation in predation risk is a major driver of ecological and evolutionary
      change, and, in turn, of geographical variation in behaviour. While predation
      risk is rarely constant in natural populations, the extent to which variation in
      predation risk shapes individual behaviour in wild populations remains unclear.
      Here, we investigated individual differences in reproductive behaviour in 16
      Trinidadian guppy populations and related it to the observed variation in
      predator biomass each population experienced. Our results show that high
      heterogeneity in predator biomass is linked to individual behavioural
      diversification. Increased within-population heterogeneity in predator biomass is
      also associated with behavioural polymorphism. Some individuals adjust the
      frequency of consensual mating behaviour in response to differences in sex ratio
      context, while others display constantly at elevated frequencies. This pattern is
      analogous to a 'live fast, die young' pace-of-life syndrome. Notably, both high
      and low mean differences in predator biomass led to a homogenization of
      individual frequency of consensual mating displays. Overall, our results
      demonstrate that individual behavioural variation is associated with
      heterogeneity in predator biomass, but not necessarily with changes in mean
      values of predator biomass. We suggest that heterogeneity in predator biomass is
      an informative predictor of adaptive responses to changes in biotic conditions.

PMID- 29321294
TI  - Model recommendations meet management reality: implementation and evaluation of a
      network-informed vaccination effort for endangered Hawaiian monk seals.
AB  - Where disease threatens endangered wildlife populations, substantial resources
      are required for management actions such as vaccination. While network models
      provide a promising tool for identifying key spreaders and prioritizing efforts
      to maximize efficiency, population-scale vaccination remains rare, providing few
      opportunities to evaluate performance of model-informed strategies under
      realistic scenarios. Because the endangered Hawaiian monk seal could be heavily
      impacted by disease threats such as morbillivirus, we implemented a prophylactic
      vaccination programme. We used contact networks to prioritize vaccinating animals
      with high contact rates. We used dynamic network models to simulate morbillivirus
      outbreaks under real and idealized vaccination scenarios. We then evaluated the
      efficacy of model recommendations in this real-world vaccination project. We
      found that deviating from the model recommendations decreased the efficiency;
      requiring 44% more vaccinations to achieve a given decrease in outbreak size.
      However, we gained protection more quickly by vaccinating available animals
      rather than waiting to encounter priority seals. This work demonstrates the value
      of network models, but also makes trade-offs clear. If vaccines were limited but
      time was ample, vaccinating only priority animals would maximize herd protection.
      However, where time is the limiting factor, vaccinating additional lower-priority
      animals could more quickly protect the population.

PMID- 29321295
TI  - Direct and indirect effects of early-life environment on lifetime fitness of
      bighorn ewes.
AB  - Cohort effects, when a common environment affects long-term performance, can have
      a major impact on population dynamics. Very few studies of wild animals have
      obtained the necessary data to study the mechanisms leading to cohort effects. We
      exploited 42 years of individual-based data on bighorn sheep to test for causal
      links between birth density, body mass, age at first reproduction (AFR),
      longevity and lifetime reproductive success (LRS) using path analysis.
      Specifically, we investigated whether the effect of early-life environment on
      lifetime fitness was the result of indirect effects through body mass or direct
      effects of early-life environment on fitness. Additionally, we evaluated whether
      the effects of early-life environment were dependant on the environment
      experienced during adulthood. Contrary to expectation, the effect on LRS mediated
      through body mass was weak compared to the effects found via a delay in AFR,
      reduced longevity and the direct effect of birth density. Birth density also had
      an important indirect effect on LRS through reduced longevity, but only when
      adult density was high. Our results show that the potential long-term
      consequences of a harsh early-life environment on fitness are likely to be
      underestimated if investigations are limited to body mass instead of fitness at
      several life stages, or if the interactions between past and present environment
      are ignored.

PMID- 29321296
TI  - Substrate growth dynamics and biomineralization of an Ediacaran encrusting
      poriferan.
AB  - The ability to encrust in order to secure and maintain growth on a substrate is a
      key competitive innovation in benthic metazoans. Here we describe the substrate
      growth dynamics, mode of biomineralization and possible affinity of Namapoikia
      rietoogensis, a large (up to 1 m), robustly skeletal, and modular Ediacaran
      metazoan which encrusted the walls of synsedimentary fissures within microbial
      metazoan reefs. Namapoikia formed laminar or domal morphologies with an internal
      structure of open tubules and transverse elements, and had a very plastic, non
      deterministic growth form which could encrust both fully lithified surfaces as
      well as living microbial substrates, the latter via modified skeletal holdfasts.
      Namapoikia shows complex growth interactions and substrate competition with
      contemporary living microbialites and thrombolites, including the production of
      plate-like dissepiments in response to microbial overgrowth which served to
      elevate soft tissue above the microbial surface. Namapoikia could also recover
      from partial mortality due to microbial fouling. We infer initial skeletal growth
      to have propagated via the rapid formation of an organic scaffold via a basal
      pinacoderm prior to calcification. This is likely an ancient mode of
      biomineralization with similarities to the living calcified demosponge Vaceletia.
      Namapoikia also shows inferred skeletal growth banding which, combined with its
      large size, implies notable individual longevity. In sum, Namapoikia was a large,
      relatively long-lived Ediacaran clonal skeletal metazoan that propagated via an
      organic scaffold prior to calcification, enabling rapid, effective and dynamic
      substrate occupation and competition in cryptic reef settings. The open tubular
      internal structure, highly flexible, non-deterministic skeletal organization, and
      inferred style of biomineralization of Namapoikia places probable affinity within
      total-group poriferans.

PMID- 29321297
TI  - Gradual plasticity alters population dynamics in variable environments: thermal
      acclimation in the green alga Chlamydomonas reinhartdii.
AB  - Environmental variability is ubiquitous, but its effects on populations are not
      fully understood or predictable. Recent attention has focused on how rapid
      evolution can impact ecological dynamics via adaptive trait change. However, the
      impact of trait change arising from plastic responses has received less
      attention, and is often assumed to optimize performance and unfold on a separate,
      faster timescale than ecological dynamics. Challenging these assumptions, we
      propose that gradual plasticity is important for ecological dynamics, and present
      a study of the plastic responses of the freshwater green algae Chlamydomonas
      reinhardtii as it acclimates to temperature changes. First, we show that C.
      reinhardtii's gradual acclimation responses can both enhance and suppress its
      performance after a perturbation, depending on its prior thermal history. Second,
      we demonstrate that where conventional approaches fail to predict the population
      dynamics of C. reinhardtii exposed to temperature fluctuations, a new model of
      gradual acclimation succeeds. Finally, using high-resolution data, we show that
      phytoplankton in lake ecosystems can experience thermal variation sufficient to
      make acclimation relevant. These results challenge prevailing assumptions about
      plasticity's interactions with ecological dynamics. Amidst the current emphasis
      on rapid evolution, it is critical that we also develop predictive methods
      accounting for plasticity.

PMID- 29321298
TI  - The worldwide importance of honey bees as pollinators in natural habitats.
AB  - The western honey bee (Apis mellifera) is the most frequent floral visitor of
      crops worldwide, but quantitative knowledge of its role as a pollinator outside
      of managed habitats is largely lacking. Here we use a global dataset of 80
      published plant-pollinator interaction networks as well as pollinator
      effectiveness measures from 34 plant species to assess the importance of A.
      mellifera in natural habitats. Apis mellifera is the most frequent floral visitor
      in natural habitats worldwide, averaging 13% of floral visits across all networks
      (range 0-85%), with 5% of plant species recorded as being exclusively visited by
      A. mellifera For 33% of the networks and 49% of plant species, however, A.
      mellifera visitation was never observed, illustrating that many flowering plant
      taxa and assemblages remain dependent on non-A. mellifera visitors for
      pollination. Apis mellifera visitation was higher in warmer, less variable
      climates and on mainland rather than island sites, but did not differ between its
      native and introduced ranges. With respect to single-visit pollination
      effectiveness, A. mellifera did not differ from the average non-A. mellifera
      floral visitor, though it was generally less effective than the most effective
      non-A. mellifera visitor. Our results argue for a deeper understanding of how A.
      mellifera, and potential future changes in its range and abundance, shape the
      ecology, evolution, and conservation of plants, pollinators, and their
      interactions in natural habitats.

PMID- 29321299
TI  - Host size and proximity to diseased neighbours drive the spread of a coral
      disease outbreak in Hawai'i.
AB  - Understanding how disease risk varies over time and across heterogeneous
      populations is critical for managing disease outbreaks, but this information is
      rarely known for wildlife diseases. Here, we demonstrate that variation in host
      and pathogen factors drive the direction, duration and intensity of a coral
      disease outbreak. We collected longitudinal health data for 200 coral colonies,
      and found that disease risk increased with host size and severity of diseased
      neighbours, and disease spread was highest among individuals between 5 and 20 m
      apart. Disease risk increased by 2% with every 10 cm increase in host size.
      Healthy colonies with severely diseased neighbours (greater than 75% affected
      tissue) were 1.6 times more likely to develop disease signs compared with
      colonies with moderately diseased neighbours (25-75% affected tissue). Force of
      infection ranged from 7 to 20 disease cases per 1000 colonies (mean = 15 cases
      per 1000 colonies). The effective reproductive ratio, or average number of
      secondary infections per infectious individual, ranged from 0.16 to 1.22.
      Probability of transmission depended strongly on proximity to diseased
      neighbours, which demonstrates that marine disease spread can be highly
      constrained within patch reefs.

PMID- 29321300
TI  - Tetrapod distribution and temperature rise during the Permian-Triassic mass
      extinction.
AB  - The Permian-Triassic mass extinction (PTME) had an enormous impact on life in
      three ways: by substantially reducing diversity, by reshuffling the composition
      of ecosystems and by expelling life from the tropics following episodes of
      intense global warming. But was there really an 'equatorial tetrapod gap', and
      how long did it last? Here, we consider both skeletal and footprint data, and
      find a more complex pattern: (i) tetrapods were distributed both at high and low
      latitudes during this time; (ii) there was a clear geographic disjunction through
      the PTME, with tetrapod distribution shifting 10-15 degrees  poleward; and (iii)
      there was a rapid expansion phase across the whole of Pangea following the PTME.
      These changes are consistent with a model of generalized migration of tetrapods
      to higher latitudinal, cooler regions, to escape from the superhot equatorial
      climate in the earliest Triassic, but the effect was shorter in time scale, and
      not as pronounced as had been proposed. In the recovery phase following the PTME,
      this episode of forced range expansion also appears to have promoted the
      emergence and radiation of entirely new groups, such as the archosaurs, including
      the dinosaurs.

PMID- 29321301
TI  - Plasmid stability is enhanced by higher-frequency pulses of positive selection.
AB  - Plasmids accelerate bacterial adaptation by sharing ecologically important traits
      between lineages. However, explaining plasmid stability in bacterial populations
      is challenging owing to their associated costs. Previous theoretical and
      experimental studies suggest that pulsed positive selection may explain plasmid
      stability by favouring gene mobility and promoting compensatory evolution to
      ameliorate plasmid cost. Here we test how the frequency of pulsed positive
      selection affected the dynamics of a mercury-resistance plasmid, pQBR103, in
      experimental populations of Pseudomonas fluorescens SBW25. Plasmid dynamics
      varied according to the frequency of Hg2+ positive selection: in the absence of
      Hg2+ plasmids declined to low frequency, whereas pulses of Hg2+ selection allowed
      plasmids to sweep to high prevalence. Compensatory evolution to ameliorate the
      cost of plasmid carriage was widespread across the entire range of Hg2+ selection
      regimes, including both constant and pulsed Hg2+ selection. Consistent with
      theoretical predictions, gene mobility via conjugation appeared to play a greater
      role in promoting plasmid stability under low-frequency pulses of Hg2+ selection.
      However, upon removal of Hg2+ selection, plasmids which had evolved under low
      frequency pulse selective regimes declined over time. Our findings suggest that
      temporally variable selection environments, such as those created during
      antibiotic treatments, may help to explain the stability of mobile plasmid
      encoded resistance.

PMID- 29321302
TI  - Rapid seasonal evolution in innate immunity of wild Drosophila melanogaster.
AB  - Understanding the rate of evolutionary change and the genetic architecture that
      facilitates rapid adaptation is a current challenge in evolutionary biology.
      Comparative studies show that genes with immune function are among the most
      rapidly evolving genes across a range of taxa. Here, we use immune defence in
      natural populations of Drosophila melanogaster to understand the rate of
      evolution in natural populations and the genetics underlying rapid change. We
      probed the immune system using the natural pathogens Enterococcus faecalis and
      Providencia rettgeri to measure post-infection survival and bacterial load of
      wild D. melanogaster populations collected across seasonal time along a
      latitudinal transect along eastern North America (Massachusetts, Pennsylvania and
      Virginia). There are pronounced and repeatable changes in the immune response
      over the approximately 10 generations between spring and autumn collections, with
      a significant but less distinct difference observed among geographical locations.
      Genes with known immune function are not enriched among alleles that cycle with
      seasonal time, but the immune function of a subset of seasonally cycling alleles
      in immune genes was tested using reconstructed outbred populations. We find that
      flies containing seasonal alleles in Thioester-containing protein 3 (Tep3) have
      different functional responses to infection and that epistatic interactions among
      seasonal Tep3 and Drosomycin-like 6 (Dro6) alleles underlie the immune phenotypes
      observed in natural populations. This rapid, cyclic response to seasonal
      environmental pressure broadens our understanding of the complex ecological and
      genetic interactions determining the evolution of immune defence in natural
      populations.

PMID- 29321303
TI  - Infection and Replication of Influenza Virus at the Ocular Surface.
AB  - Although influenza viruses typically cause respiratory tract disease, some
      viruses, particularly those with an H7 hemagglutinin, have been isolated from the
      eyes of conjunctivitis cases. Previous work has shown that isolates of multiple
      subtypes from both ocular and respiratory infections are capable of replication
      in human ex vivo ocular tissues and corneal or conjunctival cell monolayers,
      leaving the determinants of ocular tropism unclear. Here, we evaluated the effect
      of several variables on tropism for ocular cells cultured in vitro and examined
      the potential effect of the tear film on viral infectivity. All viruses tested
      were able to replicate in primary human corneal epithelial cell monolayers
      subjected to aerosol inoculation. The temperature at which cells were cultured
      postinoculation minimally affected infectivity. Replication efficiency, in
      contrast, was reduced at 33 degrees C relative to that at 37 degrees C, and this
      effect was slightly greater for the conjunctivitis isolates than for the
      respiratory ones. With the exception of a seasonal H3N2 virus, the subset of
      viruses studied in multilayer corneal tissue constructs also replicated
      productively after either aerosol or liquid inoculation. Human tears
      significantly inhibited the hemagglutination of both ocular and nonocular
      isolates, but the effect on viral infectivity was more variable, with tears
      reducing the infectivity of nonocular isolates more than ocular isolates. These
      data suggest that most influenza viruses may be capable of establishing infection
      if they reach the surface of ocular cells but that this is more likely for ocular
      tropic viruses, as they are better able to maintain their infectivity during
      passage through the tear film.IMPORTANCE The potential spread of zoonotic
      influenza viruses to humans represents an important threat to public health.
      Unfortunately, despite the importance of cellular and tissue tropism to
      pathogenesis, determinants of influenza virus tropism have yet to be fully
      elucidated. Here, we sought to identify factors that limit the ability of most
      influenza viruses to cause ocular infection. Although ocular symptoms in humans
      caused by avian influenza viruses tend to be relatively mild, these infections
      are concerning due to the potential of the ocular surface to serve as a portal of
      entry for viruses that go on to establish respiratory infections. Furthermore, a
      better understanding of the factors that influence infection and replication in
      this noncanonical site may point toward novel determinants of tropism in the
      respiratory tract.

PMID- 29321304
TI  - Determinants in the Ig Variable Domain of Human HAVCR1 (TIM-1) Are Required To
      Enhance Hepatitis C Virus Entry.
AB  - Hepatitis C virus (HCV) is the leading cause of chronic hepatitis in humans.
      Several host molecules participate in HCV cell entry, but this process remains
      unclear. The complete unraveling of the HCV entry process is important to further
      understand viral pathogenesis and develop therapeutics. Human hepatitis A virus
      (HAV) cellular receptor 1 (HAVCR1), CD365, also known as TIM-1, functions as a
      phospholipid receptor involved in cell entry of several enveloped viruses. Here,
      we studied the role of HAVCR1 in HCV infection. HAVCR1 antibody inhibited entry
      in a dose-dependent manner. HAVCR1 soluble constructs neutralized HCV, which did
      not require the HAVCR1 mucinlike region and was abrogated by a mutation of N to A
      at position 94 (N94A) in the Ig variable (IgV) domain phospholipid-binding
      pocket, indicating a direct interaction of the HAVCR1 IgV domain with HCV
      virions. However, knockout of HAVCR1 in Huh7 cells reduced but did not prevent
      HCV growth. Interestingly, the mouse HAVCR1 ortholog, also a phospholipid
      receptor, did not enhance infection and a soluble form failed to neutralize HCV,
      although replacement of the mouse IgV domain with the human HAVCR1 IgV domain
      restored the enhancement of HCV infection. Mutations in the cytoplasmic tail
      revealed that direct HAVCR1 signaling is not required to enhance HCV infection.
      Our data show that the phospholipid-binding function and other determinant(s) in
      the IgV domain of human HAVCR1 enhance HCV infection. Although the exact
      mechanism is not known, it is possible that HAVCR1 facilitates entry by
      stabilizing or enhancing attachment, leading to direct interactions with specific
      receptors, such as CD81.IMPORTANCE Hepatitis C virus (HCV) enters cells through a
      multifaceted process. We identified the human hepatitis A virus cellular receptor
      1 (HAVCR1), CD365, also known as TIM-1, as a facilitator of HCV entry. Antibody
      blocking and silencing or knockout of HAVCR1 in hepatoma cells reduced HCV entry.
      Our findings that the interaction of HAVCR1 with HCV early during infection
      enhances entry but is not required for infection support the hypothesis that
      HAVCR1 facilitates entry by stabilizing or enhancing virus binding to the cell
      surface membrane and allowing the correct virus-receptor positioning for
      interaction with the main HCV receptors. Furthermore, our data show that in
      addition to the phospholipid-binding function of HAVCR1, the enhancement of HCV
      infection involves other determinants in the IgV domain of HAVCR1. These findings
      expand the repertoire of molecules that HCV uses for cell entry, adding to the
      already complex mechanism of HCV infection and pathogenesis.

PMID- 29321305
TI  - Arabidopsis RNA Polymerase V Mediates Enhanced Compaction and Silencing of
      Geminivirus and Transposon Chromatin during Host Recovery from Infection.
AB  - Plants employ RNA-directed DNA methylation (RdDM) and dimethylation of histone 3
      lysine 9 (H3K9me2) to silence geminiviruses and transposable elements (TEs). We
      previously showed that canonical RdDM (Pol IV-RdDM) involving RNA polymerases IV
      and V (Pol IV and Pol V) is required for Arabidopsis thaliana to recover from
      infection with Beet curly top virus lacking a suppressor protein that inhibits
      methylation (BCTV L2-). Recovery, which is characterized by reduced viral DNA
      levels and symptom remission, allows normal floral development. Here, we used
      formaldehyde-assisted isolation of regulatory elements (FAIRE) to confirm that
      >90% of BCTV L2- chromatin is highly compacted during recovery, and a micrococcal
      nuclease-chromatin immunoprecipitation assay showed that this is largely due to
      increased nucleosome occupancy. Physical compaction correlated with augmented
      cytosine and H3K9 methylation and with reduced viral gene expression. We
      additionally demonstrated that these phenomena are dependent on Pol V and by
      extension the Pol IV-RdDM pathway. BCTV L2- was also used to evaluate the impact
      of viral infection on host loci, including repressed retrotransposons Ta3 and
      Athila6A Remarkably, an unexpected Pol V-dependent hypersuppression of these TEs
      was observed, resulting in transcript levels even lower than those detected in
      uninfected plants. Hypersuppression is likely to be especially important for
      natural recovery from wild-type geminiviruses, as viral L2 and AL2 proteins cause
      ectopic TE expression. Thus, Pol IV-RdDM targets both viral and TE chromatin
      during recovery, simultaneously silencing the majority of viral genomes and
      maintaining host genome integrity by enforcing tighter control of TEs in future
      reproductive tissues.IMPORTANCE In plants, RdDM pathways use small RNAs to target
      cytosine and H3K9 methylation, thereby silencing DNA virus genomes and
      transposable elements (TEs). Further, Pol IV-RdDM involving Pol IV and Pol V is a
      key aspect of host defense that can lead to recovery from geminivirus infection.
      Recovery is characterized by reduced viral DNA levels and symptom remission and
      thus allows normal floral development. Studies described here demonstrate that
      the Pol V-dependent enhanced viral DNA and histone methylation observed during
      recovery result in increased chromatin compaction and suppressed gene expression.
      In addition, we show that TE-associated chromatin is also targeted for
      hypersuppression during recovery, such that TE transcripts are reduced below the
      already low levels seen in uninfected plants. Thus, Pol IV-RdDM at once silences
      the majority of viral genomes and enforces a tight control over TEs which might
      otherwise jeopardize genome integrity in future reproductive tissue.

PMID- 29321306
TI  - Digitoxin Suppresses Human Cytomegalovirus Replication via Na+, K+/ATPase alpha1
      Subunit-Dependent AMP-Activated Protein Kinase and Autophagy Activation.
AB  - Host-directed therapeutics for human cytomegalovirus (HCMV) requires elucidation
      of cellular mechanisms that inhibit HCMV. We report a novel pathway used by
      cardiac glycosides to inhibit HCMV replication: induction of AMP-activated
      protein kinase (AMPK) activity and autophagy flux through the Na+,K+/ATPase
      alpha1 subunit. Our data illustrate an intricate balance between the autophagy
      regulators AMPK, mammalian target of rapamycin (mTOR), and ULK1 during infection
      and treatment with the cardiac glycoside digitoxin. Both infection and digitoxin
      induced AMPK phosphorylation, but ULK1 was differentially phosphorylated at
      unique sites leading to opposing effects on autophagy. Suppression of autophagy
      during infection occurred via ULK1 phosphorylation at Ser757 by enhanced mTOR
      activity. Digitoxin continuously phosphorylated AMPK, leading to ULK1
      phosphorylation at Ser317, and suppressed mTOR, resulting in increased autophagy
      flux and HCMV inhibition. In ATG5-deficient human fibroblasts, digitoxin did not
      inhibit HCMV, supporting autophagy induction as a mechanism for virus inhibition.
      Drug combination studies with digitoxin and 5-aminoimidazole-4-carboxamide
      ribonucleotide (AICAR) further confirmed the role of autophagy activation in HCMV
      inhibition. Individually, each compound phosphorylated AMPK, but their
      combination reduced autophagy rather than inducing it and was antagonistic
      against HCMV, resulting in virus replication. The initial ULK1 activation by
      digitoxin was counteracted by AICAR, which prevented the downstream interaction
      of Beclin1 and phosphatidylinositol 3-kinase class III (PI3K-CIII), further
      supporting digitoxin-mediated HCMV inhibition through autophagy. Finally, the
      alpha1 subunit was required for autophagy induction, since in alpha1-deficient
      cells neither AMPK nor autophagy was activated and HCMV was not inhibited by
      digitoxin. In summary, induction of a novel pathway (alpha1-AMPK-ULK1) induces
      autophagy as a host-directed strategy for HCMV inhibition.IMPORTANCE Infection
      with human cytomegalovirus (HCMV) creates therapeutic challenges in congenitally
      infected children and transplant recipients. Side effects and selection of
      resistant mutants with the limited drugs available prompted evaluation of host
      directed therapeutics. We report a novel mechanism of HCMV inhibition by the
      cardiac glycoside digitoxin. At low concentrations that inhibit HCMV, digitoxin
      induced signaling through the alpha1 subunit of the Na+,K+/ATPase pump and the
      cellular kinase AMPK, resulting in binding and phosphorylation of ULK1 (Ser317)
      and autophagy activation. HCMV suppressed autophagy through ULK1 phosphorylation
      (Ser757) by activating the mTOR kinase. The pump-autophagy pathway was required
      for HCMV inhibition, since in alpha1- or ATG5-deficient cells the virus was not
      inhibited. Furthermore, the AMPK activator AICAR antagonized digitoxin activity
      against HCMV, a phenomenon resulting from opposing effects downstream in the
      autophagy pathway, at the Beclin1 stage. In summary, autophagy may provide a
      strategy for harnessing HCMV replication.

PMID- 29321307
TI  - Kaposi's Sarcoma-Associated Herpesvirus K8 Is an RNA Binding Protein That
      Regulates Viral DNA Replication in Coordination with a Noncoding RNA.
AB  - KSHV lytic replication and constant primary infection of fresh cells are crucial
      for viral tumorigenicity. Virus-encoded b-Zip family protein K8 plays an
      important role in viral DNA replication in both viral reactivation and de novo
      infection. The mechanism underlying the functional role of K8 in the viral life
      cycle is elusive. Here we report that K8 is a RNA binding protein, which also
      associates with many proteins including other RNA binding proteins. Many K8
      involved protein-protein interactions are mediated by RNA. Using a crosslinking
      and immunoprecipitation (CLIP) procedure combined with high-throughput
      sequencing, RNAs that are associated with K8 in BCBL-1 cells were identified,
      that include both viral (PAN, T1.4, T0.7 and etc.) and cellular (MALAT-1, MRP,
      7SK and etc.) RNAs. An RNA-binding motif in K8 was defined, and mutation of the
      motif abolished the ability of K8 binding to many noncoding RNAs as well as viral
      DNA replication during de novo infection, suggesting that the K8 functions in
      viral replication are carried out through RNA association. The function of K8 and
      associated T1.4 RNA was investigated in details and results showed that T1.4
      mediates the binding of K8 with ori-Lyt DNA. T1.4-K8 complex physically bound to
      KSHV ori-Lyt DNA and recruited other proteins and cofactors to assemble
      replication complex. Depletion of T1.4 abolished the DNA replication in primary
      infection. These findings provide mechanistic insights into the role of K8 in
      coordination with T1.4 RNA in regulating KSHV DNA replication during de novo
      infection.ImportanceGenome wide analyses of the mammalian transcriptome revealed
      that a large proportion of sequence previously annotated as noncoding region are
      actually transcribed and give rise to stable RNAs. Emergence of a large number of
      noncoding RNAs suggests that functional RNA-protein complexes exampled by
      ribosome or spliceosome are not ancient relics of the last riboorganism but would
      be well adapted for regulatory role in biology. K8 has been puzzled by its unique
      characteristic such as multiple regulatory roles in gene expression and DNA
      replication without DNA binding capability. This study revealed the mechanism
      underlying its regulatory role by demonstrating that K8 is an RNA binding protein
      that binds to DNA and initiate DNA replication in coordination with a noncoding
      RNA. It is suggested that many of K8 functions, if not all, are carried out
      through its associated RNAs.

PMID- 29321308
TI  - Sustained Specific and Cross-Reactive T Cell Responses to Zika and Dengue Virus
      NS3 in West Africa.
AB  - Recent studies on the role of T cells in Zika virus (ZIKV) infection have shown
      that T cell responses to Asian ZIKV infection are important for protection, and
      that previous dengue virus (DENV) exposure amplifies the protective T cell
      response to Asian ZIKV. Human T cell responses to African ZIKV infection,
      however, remain unexplored. Here, we utilized the modified anthrax toxin delivery
      system to develop a flavivirus enzyme-linked immunosorbent spot (ELISPOT) assay.
      Using human ZIKV and DENV samples from Senegal, West Africa, our results
      demonstrate specific and cross-reactive T cell responses to nonstructural protein
      3 (NS3). Specifically, we found that T cell responses to NS3 protease are ZIKV
      and DENV specific, but responses to NS3 helicase are cross-reactive. Sequential
      sample analyses revealed immune responses sustained many years after infection.
      These results have important implications for African ZIKV/DENV vaccine
      development, as well as for potential flavivirus diagnostics based on T cell
      responses.IMPORTANCE The recent Zika virus (ZIKV) epidemic in Latin America and
      the associated congenital microcephaly and Guillain-Barre syndrome have raised
      questions as to why we have not recognized these distinct clinical diseases in
      Africa. The human immunologic response to ZIKV and related flaviviruses in Africa
      represents a research gap that may shed light on the mechanisms contributing to
      protection. The goal of our study was to develop an inexpensive assay to detect
      and characterize the T cell response to African ZIKV and DENV. Our data show long
      term specific and cross-reactive human immune responses against African ZIKV and
      DENV, suggesting the usefulness of a diagnostic based on the T cell response.
      Additionally, we show that prior flavivirus exposure influences the magnitude of
      the T cell response. The identification of immune responses to African ZIKV and
      DENV is of relevance to vaccine development.

PMID- 29321309
TI  - Specific Mutations in the PB2 Protein of Influenza A Virus Compensate for the
      Lack of Efficient Interferon Antagonism of the NS1 Protein of Bat Influenza A
      Like Viruses.
AB  - Recently, two new influenza A-like viruses have been discovered in bats, A/little
      yellow-shouldered bat/Guatemala/060/2010 (HL17NL10) and A/flat-faced
      bat/Peru/033/2010 (HL18NL11). The hemagglutinin (HA)-like (HL) and neuraminidase
      (NA)-like (NL) proteins of these viruses lack hemagglutination and neuraminidase
      activities, despite their sequence and structural homologies with the HA and NA
      proteins of conventional influenza A viruses. We have now investigated whether
      the NS1 proteins of the HL17NL10 and HL18NL11 viruses can functionally replace
      the NS1 protein of a conventional influenza A virus. For this purpose, we
      generated recombinant influenza A/Puerto Rico/8/1934 (PR8) H1N1 viruses
      containing the NS1 protein of the PR8 wild-type, HL17NL10, and HL18NL11 viruses.
      These viruses (r/NS1PR8, r/NS1HL17, and r/NS1HL18, respectively) were tested for
      replication in bat and nonbat mammalian cells and in mice. Our results
      demonstrate that the r/NS1HL17 and r/NS1HL18 viruses are attenuated in vitro and
      in vivo However, the bat NS1 recombinant viruses showed a phenotype similar to
      that of the r/NS1PR8 virus in STAT1-/- human A549 cells and mice, both in vitro
      and in vivo systems being unable to respond to interferon (IFN). Interestingly,
      multiple mouse passages of the r/NS1HL17 and r/NS1HL18 viruses resulted in
      selection of mutant viruses containing single amino acid mutations in the viral
      PB2 protein. In contrast to the parental viruses, virulence and IFN antagonism
      were restored in the selected PB2 mutants. Our results indicate that the NS1
      protein of bat influenza A-like viruses is less efficient than the NS1 protein of
      its conventional influenza A virus NS1 counterpart in antagonizing the IFN
      response and that this deficiency can be overcome by the influenza virus PB2
      protein.IMPORTANCE Significant gaps in our understanding of the basic features of
      the recently discovered bat influenza A-like viruses HL17NL10 and HL18NL11
      remain. The basic biology of these unique viruses displays both similarities to
      and differences from the basic biology of conventional influenza A viruses. Here,
      we show that recombinant influenza A viruses containing the NS1 protein from
      HL17NL10 and HL18NL11 are attenuated. This attenuation was mediated by their
      inability to antagonize the type I IFN response. However, this deficiency could
      be compensated for by single amino acid replacements in the PB2 gene. Our results
      unravel a functional divergence between the NS1 proteins of bat influenza A-like
      and conventional influenza A viruses and demonstrate an interplay between the
      viral PB2 and NS1 proteins to antagonize IFN.

PMID- 29321310
TI  - Therapeutic Efficacy of Vectored PGT121 Gene Delivery in HIV-1-Infected Humanized
      Mice.
AB  - Broadly neutralizing antibodies (bNAbs) are being explored for HIV-1 prevention
      and cure strategies. However, administration of purified bNAbs poses challenges
      in resource-poor settings, where the HIV-1 disease burden is greatest. In vivo
      vector-based production of bNAbs represents an alternative strategy. We
      investigated adenovirus serotype 5 (Ad5) and adeno-associated virus serotype 1
      (AAV1) vectors to deliver the HIV-1-specific bNAb PGT121 in wild-type and
      immunocompromised C57BL/6 mice as well as in HIV-1-infected bone marrow-liver
      thymus (BLT) humanized mice. Ad5.PGT121 and AAV1.PGT121 produced functional
      antibody in vivo Ad5.PGT121 produced PGT121 rapidly within 6 h, whereas
      AAV1.PGT121 produced detectable PGT121 in serum by 72 h. Serum PGT121 levels were
      rapidly reduced by the generation of anti-PGT121 antibodies in immunocompetent
      mice but were durably maintained in immunocompromised mice. In HIV-1-infected BLT
      humanized mice, Ad5.PGT121 resulted in a greater reduction of viral loads than
      did AAV1.PGT121. Ad5.PGT121 also led to more-sustained virologic control than
      purified PGT121 IgG. Ad5.PGT121 afforded more rapid, robust, and durable
      antiviral efficacy than AAV1.PGT121 and purified PGT121 IgG in HIV-1-infected
      humanized mice. Further evaluation of vector delivery of HIV-1 bNAbs is
      warranted, although approaches to prevent the generation of antiantibody
      responses may also be required.IMPORTANCE Broadly neutralizing antibodies (bNAbs)
      are being explored for HIV-1 prevention and cure strategies, but delivery of
      purified antibodies may prove challenging. We investigated adenovirus serotype 5
      (Ad5) and adeno-associated virus serotype 1 (AAV1) vectors to deliver the HIV-1
      specific bNAb PGT121. Ad5.PGT121 afforded more rapid, robust, and durable
      antiviral efficacy than AAV1.PGT121 and purified PGT121 IgG in HIV-1-infected
      humanized mice.

PMID- 29321311
TI  - Herpes Simplex Virus 1 Mutant with Point Mutations in UL39 Is Impaired for Acute
      Viral Replication in Mice, Establishment of Latency, and Explant-Induced
      Reactivation.
AB  - In the process of generating herpes simplex virus 1 (HSV-1) mutations in the
      viral regulatory gene encoding infected cell protein 0 (ICP0), we isolated a
      viral mutant, termed KOS-NA, that was severely impaired for acute replication in
      the eyes and trigeminal ganglia (TG) of mice, defective in establishing a latent
      infection, and reactivated poorly from explanted TG. To identify the secondary
      mutation(s) responsible for the impaired phenotypes of this mutant, we sequenced
      the KOS-NA genome and noted that it contained two nonsynonymous mutations in
      UL39, which encodes the large subunit of ribonucleotide reductase, ICP6. These
      mutations resulted in lysine-to-proline (residue 393) and arginine-to-histidine
      (residue 950) substitutions in ICP6. To determine whether alteration of these
      amino acids was responsible for the KOS-NA phenotypes in vivo, we recombined the
      wild-type UL39 gene into the KOS-NA genome and rescued its acute replication
      phenotypes in mice. To further establish the role of UL39 in KOS-NA's decreased
      pathogenicity, the UL39 mutations were recombined into HSV-1 (generating
      UL39mut), and this mutant virus showed reduced ocular and TG replication in mice
      comparable to that of KOS-NA. Interestingly, ICP6 protein levels were reduced in
      KOS-NA-infected cells relative to the wild-type protein. Moreover, we observed
      that KOS-NA does not counteract caspase 8-induced apoptosis, unlike wild-type
      strain KOS. Based on alignment studies with other HSV-1 ICP6 homologs, our data
      suggest that amino acid 950 of ICP6 likely plays an important role in ICP6
      accumulation and inhibition of apoptosis, consequently impairing HSV-1
      pathogenesis in a mouse model of HSV-1 infection.IMPORTANCE HSV-1 is a major
      human pathogen that infects ~80% of the human population and can be life
      threatening to infected neonates or immunocompromised individuals. Effective
      therapies for treatment of recurrent HSV-1 infections are limited, which
      emphasizes a critical need to understand in greater detail the events that
      modulate HSV-1 replication and pathogenesis. In the current study, we identified
      a neuroattenuated HSV-1 mutant (i.e., KOS-NA) that contains novel mutations in
      the UL39 gene, which codes for the large subunit of ribonucleotide reductase
      (also known as ICP6). This mutant form of ICP6 was responsible for the
      attenuation of KOS-NA in vivo and resulted in diminished ICP6 protein levels and
      antiapoptotic effect. Thus, we have determined that subtle alteration of the UL39
      gene regulates expression and functions of ICP6 and severely impacts HSV-1
      pathogenesis, potentially making KOS-NA a promising vaccine candidate against HSV
      1.

PMID- 29321312
TI  - The E3 Ubiquitin Ligase Siah-1 Suppresses Avian Reovirus Infection by Targeting
      p10 for Degradation.
AB  - Avian reovirus (ARV) causes viral arthritis, chronic respiratory diseases,
      retarded growth, and malabsorption syndrome. The ARV p10 protein, a viroporin
      responsible for the induction of cell syncytium formation and apoptosis, is
      rapidly degraded in host cells. Our previous report demonstrated that cellular
      lysosome-associated membrane protein 1 (LAMP-1) interacted with p10 and was
      involved in its degradation. However, the molecular mechanism underlying LAMP-1
      mediated p10 degradation remains elusive. We report here that the E3 ubiquitin
      ligase seven in absentia homolog 1 (Siah-1) is critical for p10 ubiquitylation.
      Our data show that Siah-1 ubiquitylated p10 and targeted it for proteasome
      degradation. Furthermore, the ubiquitylation of p10 by Siah-1 required the
      participation of LAMP-1 by forming a multicomponent complex. Thus, LAMP-1
      promotes the proteasomal degradation of p10 via interacting with both p10 and the
      E3 ligase Siah-1. These data establish a novel host defense mechanism where LAMP
      1 serves as a scaffold for both Siah-1 and p10 that allows the E3 ligase
      targeting p10 for ubiquitylation and degradation to suppress ARV
      infection.IMPORTANCE Avian reovirus (ARV) is an important poultry pathogen
      causing viral arthritis, chronic respiratory diseases, retarded growth, and
      malabsorption syndrome, leading to considerable economic losses to the poultry
      industry across the globe. The ARV p10 protein is a virulence factor responsible
      for the induction of cell syncytium formation and apoptosis and is rapidly
      degraded in host cells. We previously found that cellular lysosome-associated
      membrane protein 1 (LAMP-1) interacts with p10 and is involved in its
      degradation. Here we report that the E3 ubiquitin ligase seven in absentia
      homolog 1 (Siah-1) ubiquitylated p10 and targeted it for proteasomal degradation.
      Furthermore, the ubiquitylation of p10 by Siah-1 required the participation of
      LAMP-1 by forming a multicomponent complex. Thus, LAMP-1 serves as an adaptor to
      allow Siah-1 to target p10 for degradation, thereby suppressing ARV growth in
      host cells.

PMID- 29321313
TI  - TIP60 Complex Inhibits Hepatitis B Virus Transcription.
AB  - Hepatitis B virus (HBV) is a global major health problem, with over one million
      deaths annually caused by chronic liver damage. Understanding host factors that
      modulate HBV replication may aid the development of anti-HBV therapies. Our
      recent genome-wide small interfering RNA screen using recombinant HBV
      demonstrated that TIP60 inhibited HBV infection. Here, we show that TIP60 complex
      contributes to anti-HBV defense. The TIP60 complex bound to the HBV promoter and
      suppressed HBV transcription driven by the precore/core promoter. The silencing
      of EP400, TRRAP, BAF53a, RUVBL1, and RUVBL2, which form the TIP60 complex, also
      resulted in increased HBV transcription. These results contribute to our enhanced
      understanding of the molecular mechanism of HBV transcription associated with the
      chromatin structure of HBV covalently closed circular DNA (cccDNA). Exploiting
      these intrinsic cellular defenses might help develop new anti-HBV
      agents.IMPORTANCE Investigating the molecular mechanism of HBV replication is
      important to understand the persistent nature of HBV infection and to aid the
      development of new HBV agents, which are currently limited to HBV polymerase
      inhibitors. Previously, we developed a new reporter HBV. By screening host
      factors using this recombinant virus, we identified several gene products that
      regulate HBV infection, including TIP60. Here, we showed that TIP60, a catalytic
      subunit of the NuA4 complex, inhibited HBV replication. Depletion of TIP60
      increased the level of HBV mRNA. Moreover, TIP60 localized in the HBV cccDNA
      chromatin complex catalyzed the acetylation of histone H4 to recruit Brd4. These
      results suggest that TIP60, in concert with other cellular factors, plays an
      important role in the regulation of the HBV chromatin structure by acting as a
      critical component of the intrinsic antiviral defense, which sheds new light on
      the regulation of HBV replication.

PMID- 29321314
TI  - HLA Class I Downregulation by HIV-1 Variants from Subtype C Transmission Pairs.
AB  - HIV-1 downregulates HLA-A and HLA-B from the surface of infected cells primarily
      to evade CD8 T cell recognition. HLA-C was thought to remain on the cell surface
      and bind inhibitory killer immunoglobulin-like receptors, preventing NK cell
      mediated suppression. However, a recent study found HIV-1 primary viruses have
      the capacity to downregulate HLA-C. The goal of this study was to assess the
      heterogeneity of HLA-A, HLA-B and HLA-C downregulation among full-length primary
      viruses from six chronically infected and six newly infected individuals from
      transmission pairs, and to determine whether transmitted/founder variants exhibit
      common HLA class I downregulation characteristics. We measured HLA-A, HLA-B, HLA
      C and total HLA class I downregulation by flow cytometry of primary CD4 T cells
      infected with 40 infectious molecular clones. Primary viruses mediated a range of
      HLA class I downregulation capacities (1.3-6.1-fold), which could differ
      significantly between transmission pairs. Downregulation of HLA-C surface
      expression on infected cells correlated with susceptibility to in vitro NK cell
      suppression of virus release. Despite this, transmitted/founder variants did not
      share a common downregulation signature and instead were more similar to the
      quasispecies of matched donor partners. These data indicate that a range of viral
      abilities to downregulate HLA-A, HLA-B and HLA-C exist within and between
      individuals, which can have functional consequences on immune
      recognition.IMPORTANCE Subtype C HIV-1 is the predominant subtype involved in
      heterosexual transmission in Sub-Saharan Africa. Authentic subtype C viruses that
      contain natural sequence variations throughout the genome are often not used in
      experimental systems, due to technical constraints and sample availability. In
      this study, authentic full-length subtype C viruses, including
      transmitted/founder viruses, were examined for the ability to disrupt surface
      expression of human leukocyte antigen (HLA) class I molecules, which are central
      to both adaptive and innate immune responses to viral infections. We found that
      HLA class I downregulation capacity of primary viruses varied, and HLA-C
      downregulation capacity impacted viral suppression by natural killer cells.
      Transmitted viruses were not distinct in the capacity for HLA class I
      downregulation or natural killer cell evasion. These results enrich our
      understanding of the phenotypic variation existing among natural HIV-1 viruses,
      and how that might impact the ability of the immune system to recognize infected
      cells in acute and chronic infection.

PMID- 29321315
TI  - Paramyxovirus V Proteins Interact with the RIG-I/TRIM25 Regulatory Complex and
      Inhibit RIG-I Signaling.
AB  - Paramyxovirus V proteins are known antagonists of the RIG-I-like receptor (RLR)
      mediated interferon induction pathway, interacting with and inhibiting the RLR
      MDA5. We report interactions between the Nipah virus V protein and both RIG-I
      regulatory protein TRIM25 and RIG-I. We also observed interactions between these
      host proteins and the V proteins of measles virus, Sendai virus, and
      parainfluenza virus. These interactions are mediated by the conserved C-terminal
      domain of the V protein, which binds to the tandem caspase activation and
      recruitment domains (CARDs) of RIG-I (the region of TRIM25 ubiquitination) and to
      the SPRY domain of TRIM25, which mediates TRIM25 interaction with the RIG-I
      CARDs. Furthermore, we show that V interaction with TRIM25 and RIG-I prevents
      TRIM25-mediated ubiquitination of RIG-I and disrupts downstream RIG-I signaling
      to the mitochondrial antiviral signaling protein. This is a novel mechanism for
      innate immune inhibition by paramyxovirus V proteins, distinct from other known V
      protein functions such as MDA5 and STAT1 antagonism.IMPORTANCE The host RIG-I
      signaling pathway is a key early obstacle to paramyxovirus infection, as it
      results in rapid induction of an antiviral response. This study shows that
      paramyxovirus V proteins interact with and inhibit the activation of RIG-I,
      thereby interrupting the antiviral signaling pathway and facilitating virus
      replication.

PMID- 29321316
TI  - Two Residues in NSP9 Contribute to the Enhanced Replication and Pathogenicity of
      Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus.
AB  - Highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV)
      possesses greater replicative capacity and pathogenicity than classical PRRSV.
      However, the factors that lead to enhanced replication and pathogenicity remain
      unclear. In our study, an alignment of all available full-length sequences of
      North American-type PRRSVs (n = 204) revealed two consistent amino acid mutations
      that differed between HP-PRRSV and classical PRRSV and were located at positions
      519 and 544 in nonstructural protein 9. Next, a series of mutant viruses with
      either single or double amino acid replacements were generated from HP-PRRSV HuN4
      and classical PRRSV CH-1a infectious cDNA clones. Deletion of either of the amino
      acids led to a complete loss of virus viability. In both Marc-145 and porcine
      alveolar macrophages, the replicative efficiencies of mutant viruses based on
      HuN4 were reduced compared to the parent, whereas the replication level of CH-1a
      derived mutant viruses was increased. Plaque growth assays showed clear
      differences between mutant and parental viruses. In infected piglets, the
      pathogenicity of HuN4-derived mutant viruses, assessed through clinical symptoms,
      viral load in sera, histopathology examination, and thymus atrophy, was reduced.
      Our results indicate that the amino acids at positions 519 and 544 in NSP9 are
      involved in the replication efficiency of HP-PRRSV and contribute to enhanced
      pathogenicity. This study is the first to identify specific amino acids involved
      in PRRSV replication or pathogenicity. These findings will contribute to
      understanding the molecular mechanisms of PRRSV replication and pathogenicity,
      leading to better therapeutic and prognostic options to combat the
      virus.IMPORTANCE Porcine reproductive and respiratory syndrome (PRRS), caused by
      porcine reproductive and respiratory syndrome virus (PRRSV), is a significant
      threat to the global pig industry. Highly pathogenic PRRSV (HP-PRRSV) first
      emerged in China in 2006 and has subsequently spread across Asia, causing
      considerable damage to local economies. HP-PRRSV strains possess a greater
      replication capacity and higher pathogenicity than classical PRRSV strains,
      although the mechanisms that underlie these characteristics are unclear. In the
      present study, we identified two mutations in HP-PRRSV strains that distinguish
      them from classical PRRSV strains. Further experiments that swapped the two
      mutations in an HP-PRRSV strain and a classical PRRSV strain demonstrated that
      they are involved in the replication efficiency of the virus and its virulence.
      Our findings have important implications for understanding the molecular
      mechanisms of PRRSV replication and pathogenicity and also provide new avenues of
      research for the study of other viruses.

PMID- 29321318
TI  - Viperin Restricts Zika Virus and Tick-Borne Encephalitis Virus Replication by
      Targeting NS3 for Proteasomal Degradation.
AB  - Flaviviruses are arthropod-borne viruses that constitute a major global health
      problem, with millions of human infections annually. Their pathogenesis ranges
      from mild illness to severe manifestations such as hemorrhagic fever and fatal
      encephalitis. Type I interferons (IFNs) are induced in response to viral
      infection and stimulate the expression of interferon-stimulated genes (ISGs),
      including that encoding viperin (virus-inhibitory protein, endoplasmic reticulum
      associated, IFN inducible), which shows antiviral activity against a broad
      spectrum of viruses, including several flaviviruses. Here we describe a novel
      antiviral mechanism employed by viperin against two prominent flaviviruses, tick
      borne encephalitis virus (TBEV) and Zika virus (ZIKV). Viperin was found to
      interact and colocalize with the structural proteins premembrane (prM) and
      envelope (E) of TBEV, as well as with nonstructural (NS) proteins NS2A, NS2B, and
      NS3. Interestingly, viperin expression reduced the NS3 protein level, and the
      stability of the other interacting viral proteins, but only in the presence of
      NS3. We also found that although viperin interacted with NS3 of mosquito-borne
      flaviviruses (ZIKV, Japanese encephalitis virus, and yellow fever virus), only
      ZIKV was sensitive to the antiviral effect of viperin. This sensitivity
      correlated with viperin's ability to induce proteasome-dependent degradation of
      NS3. ZIKV and TBEV replication was rescued completely when NS3 was overexpressed,
      suggesting that the viral NS3 is the specific target of viperin. In summary, we
      present here a novel antiviral mechanism of viperin that is selective for
      specific viruses in the genus Flavivirus, affording the possible availability of
      new drug targets that can be used for therapeutic intervention.IMPORTANCE
      Flaviviruses are a group of enveloped RNA viruses that cause severe diseases in
      humans and animals worldwide, but no antiviral treatment is yet available.
      Viperin, a host protein produced in response to infection, effectively restricts
      the replication of several flaviviruses, but the exact molecular mechanisms have
      not been elucidated. Here we have identified a novel mechanism employed by
      viperin to inhibit the replication of two flaviviruses: tick-borne encephalitis
      virus (TBEV) and Zika virus (ZIKV). Viperin induced selective degradation via the
      proteasome of TBEV and ZIKV nonstructural 3 (NS3) protein, which is involved in
      several steps of the viral life cycle. Furthermore, viperin also reduced the
      stability of several other viral proteins in a NS3-dependent manner, suggesting a
      central role of NS3 in viperin's antiflavivirus activity. Taking the results
      together, our work shows important similarities and differences among the members
      of the genus Flavivirus and could lead to the possibility of therapeutic
      intervention.

PMID- 29321317
TI  - The Wnt Signaling Pathway Is Differentially Expressed during the Bovine
      Herpesvirus 1 Latency-Reactivation Cycle: Evidence That Two Protein Kinases
      Associated with Neuronal Survival, Akt3 and BMPR2, Are Expressed at Higher Levels
      during Latency.
AB  - Sensory neurons in trigeminal ganglia (TG) of calves latently infected with
      bovine herpesvirus 1 (BoHV-1) abundantly express latency-related (LR) gene
      products, including a protein (ORF2) and two micro-RNAs. Recent studies in mouse
      neuroblastoma cells (Neuro-2A) demonstrated ORF2 interacts with beta-catenin and
      a beta-catenin coactivator, high-mobility group AT-hook 1 (HMGA1) protein, which
      correlates with increased beta-catenin-dependent transcription and cell survival.
      beta-Catenin and HMGA1 are readily detected in a subset of latently infected TG
      neurons but not TG neurons from uninfected calves or reactivation from latency.
      Consequently, we hypothesized that the Wnt/beta-catenin signaling pathway is
      differentially expressed during the latency and reactivation cycle and an active
      Wnt pathway promotes latency. RNA-sequencing studies revealed that 102 genes
      associated with the Wnt/beta-catenin signaling pathway were differentially
      expressed in TG during the latency-reactivation cycle in calves. Wnt agonists
      were generally expressed at higher levels during latency, but these levels
      decreased during dexamethasone-induced reactivation. The Wnt agonist bone
      morphogenetic protein receptor 2 (BMPR2) was intriguing because it encodes a
      serine/threonine receptor kinase that promotes neuronal differentiation and
      inhibits cell death. Another differentially expressed gene encodes a protein
      kinase (Akt3), which is significant because Akt activity enhances cell survival
      and is linked to herpes simplex virus 1 latency and neuronal survival. Additional
      studies demonstrated ORF2 increased Akt3 steady-state protein levels and
      interacted with Akt3 in transfected Neuro-2A cells, which correlated with Akt3
      activation. Conversely, expression of Wnt antagonists increased during
      reactivation from latency. Collectively, these studies suggest Wnt signaling
      cooperates with LR gene products, in particular ORF2, to promote
      latency.IMPORTANCE Lifelong BoHV-1 latency primarily occurs in sensory neurons.
      The synthetic corticosteroid dexamethasone consistently induces reactivation from
      latency in calves. RNA sequencing studies revealed 102 genes associated with the
      Wnt/beta-catenin signaling pathway are differentially regulated during the
      latency-reactivation cycle. Two protein kinases associated with the Wnt pathway,
      Akt3 and BMPR2, were expressed at higher levels during latency but were repressed
      during reactivation. Furthermore, five genes encoding soluble Wnt antagonists and
      beta-catenin-dependent transcription inhibitors were induced during reactivation
      from latency. These findings are important because Wnt, BMPR2, and Akt3 promote
      neurogenesis and cell survival, processes crucial for lifelong viral latency. In
      transfected neuroblastoma cells, a viral protein expressed during latency (ORF2)
      interacts with and enhances Akt3 protein kinase activity. These findings provide
      insight into how cellular factors associated with the Wnt signaling pathway
      cooperate with LR gene products to regulate the BoHV-1 latency-reactivation
      cycle.

PMID- 29321319
TI  - Non-structural protein sigma1s is required for optimal reovirus protein
      expression.
AB  - Reovirus non-structural protein sigma1s is required for the establishment of
      viremia and hematogenous viral dissemination. However, the function of the
      sigma1s protein during the reovirus replication cycle is not known. In this
      study, we found that sigma1s was required for efficient reovirus replication in
      SV40-immortalized endothelial cells (SVECs), mouse embryonic fibroblasts, human
      umbilical vein endothelial cells (HUVECs), and T84 human colonic epithelial
      cells. In each of these cell lines, wild type reovirus produced substantially
      higher viral titers than a sigma1s-deficient mutant. The sigma1s protein was not
      required for early events in the reovirus infection, as no difference in
      infectivity between the wild type and sigma1s-null viruses was observed. However,
      wild type virus produced markedly higher viral protein levels than the sigma1s
      deficient strain. The disparity in viral replication did not result from
      differences in viral transcription or protein stability. We further found that
      the sigma1s protein was dispensable for cell killing and induction of type-1
      interferon responses. In the absence of sigma1s, viral factory (VF) maturation
      was impaired, but sufficient to support low levels of reovirus replication.
      Together, our results indicate that sigma1s is not absolutely essential for viral
      protein production, but rather potentiates reovirus protein expression to
      facilitate reovirus replication. Our findings suggest that sigma1s enables
      hematogenous reovirus dissemination by promoting efficient viral protein
      synthesis, and thereby reovirus replication, in cells that are required for
      reovirus spread to the blood.IMPORTANCEHematogenous dissemination is critical a
      step in the pathogenesis of many viruses. For reovirus, nonstructural protein
      sigma1s is required for viral spread via the blood. However, the mechanism by
      sigma1s promotes reovirus dissemination is unknown. Here, we identified sigma1s
      as a viral mediator of reovirus protein expression. We found several cultured
      cell lines in which sigma1s is required for efficient reovirus replication. In
      these cells, wild type virus produced substantially higher levels of viral
      protein than a sigma1s-deficient mutant. The sigma1s protein was not required for
      viral mRNA transcription or viral protein stability. Owing to reduced levels of
      viral protein synthesized in the absence of sigma1s, maturation of viral
      factories was impaired and significantly fewer viral progeny were produced. Taken
      together, our findings indicate that sigma1s is required for optimal reovirus
      protein production, and thereby viral replication, in cells required hematogenous
      reovirus dissemination.

PMID- 29321321
TI  - Functional Analysis of the Dengue Virus Genome Using an Insertional Mutagenesis
      Screen.
AB  - In the last few decades, dengue virus, an arbovirus, has spread to over 120
      countries. Although a vaccine has been approved in some countries, limitations on
      its effectiveness and a lack of effective antiviral treatments reinforce the need
      for additional research. The functions of several viral nonstructural proteins
      are essentially unknown. To better understand the functions of these proteins and
      thus dengue virus pathogenesis, we embarked on a genomewide transposon
      mutagenesis screen with next-generation sequencing to determine sites in the
      viral genome that tolerate 15-nucleotide insertions. Using this approach, we
      generated support for several published predicted transmembrane and enzymatic
      domains. Next, we created 7 mutants containing the 15-nucleotide insertion from
      the original selection and found 6 of them were capable of replication in both
      mammalian and mosquito tissue culture cells. Interestingly, one mutation had a
      significant impairment of viral assembly, and this mutation may lead to a better
      understanding of viral assembly and release. In addition, we created a fully
      infectious virus expressing a functionally tagged NS4B protein, which will
      provide a much-needed tool to elucidate the role of NS4B in viral
      pathogenesis.IMPORTANCE Dengue virus is a mosquito-borne virus distributed in
      tropical and subtropical regions globally that can result in hospitalization and
      even death in some cases. Although a vaccine exists, its limitations and a lack
      of approved antiviral treatments highlight our limited understanding of dengue
      virus pathogenesis and host immunity. The functions of many viral proteins are
      poorly understood. We used a previously published approach using transposon
      mutagenesis to develop tools to study these proteins' functions by adding
      insertions randomly throughout the viral genomes. These genomes were transferred
      into cells, and infectious progeny were recovered to determine sites that
      tolerated insertions, as only the genomes that tolerated insertions would be able
      to propagate. Using these results, we created viruses with epitope tags, one in
      the viral structural protein Capsid and one in the viral nonstructural protein
      NS4B. Further investigation of these mutants may elucidate the roles of Capsid
      and NS4B during dengue virus infections.

PMID- 29321320
TI  - HIV-1-Specific IgA Monoclonal Antibodies from an HIV-1 Vaccinee Mediate
      Galactosylceramide Blocking and Phagocytosis.
AB  - Vaccine-elicited humoral immune responses comprise an array of antibody forms and
      specificities, with only a fraction contributing to protective host immunity.
      Elucidation of antibody effector functions responsible for protective immunity
      against human immunodeficiency virus type 1 (HIV-1) acquisition is a major goal
      for the HIV-1 vaccine field. Immunoglobulin A (IgA) is an important part of the
      host defense against pathogens; however, little is known about the role of
      vaccine-elicited IgA and its capacity to mediate antiviral functions. To identify
      the antiviral functions of HIV-1-specific IgA elicited by vaccination, we cloned
      HIV-1 envelope-specific IgA monoclonal antibodies (MAbs) by memory B cell
      cultures from peripheral blood mononuclear cells from an RV144 vaccinee and
      produced two IgA clonal cell lines (HG129 and HG130) producing native,
      nonrecombinant IgA MAbs. The HG129 and HG130 MAbs mediated phagocytosis by
      monocytes, and HG129 blocked HIV-1 Env glycoprotein binding to
      galactosylceramide, an alternative HIV-1 receptor. These findings elucidate
      potential antiviral functions of vaccine-elicited HIV-1 envelope-specific IgA
      that may act to block HIV-1 acquisition at the portal of entry by preventing HIV
      1 binding to galactosylceramide and mediating antibody Fc receptor-mediated
      virion phagocytosis. Furthermore, these findings highlight the complex and
      diverse interactions of vaccine-elicited IgA with pathogens that depend on IgA
      fine specificity and form (e.g., multimeric or monomeric) in the systemic
      circulation and mucosal compartments.IMPORTANCE Host-pathogen interactions in
      vivo involve numerous immune mechanisms that can lead to pathogen clearance.
      Understanding the nature of antiviral immune mechanisms can inform the design of
      efficacious HIV-1 vaccine strategies. Evidence suggests that both neutralizing
      and nonneutralizing antibodies can mediate some protection against HIV in animal
      models. Although numerous studies have characterized the functional properties of
      HIV-1-specific IgG, more studies are needed on the functional attributes of HIV-1
      specific IgA, specifically for vaccine-elicited IgA. Characterization of the
      functional properties of HIV-1 Env-specific IgA monoclonal antibodies from human
      vaccine clinical trials are critical toward understanding the capacity of the
      host immune response to block HIV-1 acquisition.

PMID- 29321322
TI  - Dengue Virus Selectively Annexes Endoplasmic Reticulum-Associated Translation
      Machinery as a Strategy for Co-opting Host Cell Protein Synthesis.
AB  - A primary question in dengue virus (DENV) biology is the molecular strategy for
      recruitment of host cell protein synthesis machinery. Here, we combined cell
      fractionation, ribosome profiling, and transcriptome sequencing (RNA-seq) to
      investigate the subcellular organization of viral genome translation and
      replication as well as host cell translation and its response to DENV infection.
      We report that throughout the viral life cycle, DENV plus- and minus-strand RNAs
      were highly partitioned to the endoplasmic reticulum (ER), identifying the ER as
      the primary site of DENV translation. DENV infection was accompanied by an ER
      compartment-specific remodeling of translation, where ER translation capacity was
      subverted from host transcripts to DENV plus-strand RNA, particularly at late
      stages of infection. Remarkably, translation levels and patterns in the cytosol
      compartment were only modestly affected throughout the experimental time course
      of infection. Comparisons of ribosome footprinting densities of the DENV plus
      strand RNA and host mRNAs indicated that DENV plus-strand RNA was only sparsely
      loaded with ribosomes. Combined, these observations suggest a mechanism where ER
      localized translation and translational control mechanisms, likely cis encoded,
      are used to repurpose the ER for DENV virion production. Consistent with this
      view, we found ER-linked cellular stress response pathways commonly associated
      with viral infection, namely, the interferon response and unfolded protein
      response, to be only modestly activated during DENV infection. These data support
      a model where DENV reprograms the ER protein synthesis and processing environment
      to promote viral survival and replication while minimizing the activation of
      antiviral and proteostatic stress response pathways.IMPORTANCE DENV, a prominent
      human health threat with no broadly effective or specific treatment, depends on
      host cell translation machinery for viral replication, immune evasion, and virion
      biogenesis. The molecular mechanism by which DENV commandeers the host cell
      protein synthesis machinery and the subcellular organization of DENV replication
      and viral protein synthesis is poorly understood. Here, we report that DENV has
      an almost exclusively ER-localized life cycle, with viral replication and
      translation largely restricted to the ER. Surprisingly, DENV infection largely
      affects only ER-associated translation, with relatively modest effects on host
      cell translation in the cytosol. DENV RNA translation is very inefficient, likely
      representing a strategy to minimize disruption of ER proteostasis. Overall these
      findings demonstrate that DENV has evolved an ER-compartmentalized life cycle;
      thus, targeting the molecular signatures and regulation of the DENV-ER
      interaction landscape may reveal strategies for therapeutic intervention.

PMID- 29321324
TI  - Influenza C and D Viruses Package Eight Organized Ribonucleoprotein Complexes.
AB  - Influenza A and B viruses have eight-segmented, single-stranded, negative-sense
      RNA genomes, whereas influenza C and D viruses have seven-segmented genomes. Each
      genomic RNA segment exists in the form of a ribonucleoprotein complex (RNP) in
      association with nucleoproteins and an RNA-dependent RNA polymerase in virions.
      Influenza D virus was recently isolated from swine and cattle, but its morphology
      is not fully studied. Here, we examined the morphological characteristics of
      D/bovine/Yamagata/10710/2016 (D/Yamagata) and C/Ann Arbor/50 (C/AA), focusing on
      RNPs packaged within the virions. By scanning transmission electron microscopic
      tomography, we found that more than 70% of D/Yamagata and C/AA virions packaged
      eight RNPs arranged in the "1+7" pattern as observed in influenza A and B
      viruses, even though type C and D virus genomes are segmented into only seven
      segments. These results imply that influenza viruses generally package eight RNPs
      arranged in the "1+7" pattern regardless of the number of RNA segments in their
      genome.IMPORTANCE The genomes of influenza A and B viruses are segmented into
      eight segments of negative-sense RNA, and those of influenza C and D viruses are
      segmented into seven segments. For progeny virions to be infectious, each virion
      needs to package all of their genomic segments. Several studies support the
      conclusion that influenza A and B viruses selectively package eight distinct
      genomic RNA segments; however, the packaging of influenza C and D viruses, which
      possess seven segmented genomes, is less understood. By using electron
      microscopy, we showed that influenza C and D viruses package eight RNA segments
      just as influenza A and B viruses do. These results suggest that influenza
      viruses prefer to package eight RNA segments within virions independent of the
      number of genome segments.

PMID- 29321323
TI  - HIV-1 Vif's Capacity To Manipulate the Cell Cycle Is Species Specific.
AB  - Cells derived from mice and other rodents exhibit profound blocks to HIV-1 virion
      production, reflecting species-specific incompatibilities between viral Tat and
      Rev proteins and essential host factors cyclin T1 (CCNT1) and exportin-1 (XPO1,
      also known as CRM1), respectively. To determine if mouse cell blocks other than
      CCNT1 and XPO1 affect HIV's postintegration stages, we studied HIV-1NL4-3 gene
      expression in mouse NIH 3T3 cells modified to constitutively express HIV-1
      compatible versions of CCNT1 and XPO1 (3T3.CX cells). 3T3.CX cells supported both
      Rev-independent and Rev-dependent viral gene expression and produced relatively
      robust levels of virus particles, confirming that CCNT1 and XPO1 represent the
      predominant blocks to these stages. Unexpectedly, however, 3T3.CX cells were
      remarkably resistant to virus-induced cytopathic effects observed in human cell
      lines, which we mapped to the viral protein Vif and its apparent species-specific
      capacity to induce G2/M cell cycle arrest. Vif was able to mediate rapid
      degradation of human APOBEC3G and the PPP2R5D regulatory B56 subunit of the PP2A
      phosphatase holoenzyme in mouse cells, thus demonstrating that VifNL4-3's
      modulation of the cell cycle can be functionally uncoupled from some of its other
      defined roles in CUL5-dependent protein degradation. Vif was also unable to
      induce G2/M cell cycle arrest in other nonhuman cell types, including cells
      derived from nonhuman primates, leading us to propose that one or more human
      specific cofactors underpin Vif's ability to modulate the cell cycle.IMPORTANCE
      Cells derived from mice and other rodents exhibit profound blocks to HIV-1
      replication, thus hindering the development of a low-cost small-animal model for
      studying HIV/AIDS. Here, we engineered otherwise-nonpermissive mouse cells to
      express HIV-1-compatible versions of two species-specific host dependency
      factors, cyclin T1 (CCNT1) and exportin-1 (XPO1) (3T3.CX cells). We show that
      3T3.CX cells rescue HIV-1 particle production but, unexpectedly, are completely
      resistant to virus-induced cytopathic effects. We mapped these effects to the
      viral accessory protein Vif, which induces a prolonged G2/M cell cycle arrest
      followed by apoptosis in human cells. Combined, our results indicate that one or
      more additional human-specific cofactors govern HIV-1's capacity to modulate the
      cell cycle, with potential relevance to viral pathogenesis in people and existing
      animal models.

PMID- 29321325
TI  - The Identification and Characterization of Sindbis Virus RNA:Host Protein
      Interactions.
AB  - Arthropod-borne viruses, such as the members of genus Alphavirus, are a
      significant concern to global public health. As obligate intracellular pathogens,
      RNA viruses must interact with the host cell machinery to establish, and
      complete, their viral lifecycles. Despite considerable efforts to define the
      host/pathogen interactions essential for alphaviral replication, an unbiased and
      inclusive assessment of alphaviral RNA:protein interactions has not been
      undertaken. Moreover, the biological and molecular importance of these
      interactions, in the full context of their molecular function as RNA-binding
      proteins, has not been fully realized. The data presented here introduces a
      robust viral RNA:protein discovery method to elucidate the Sindbis virus (SINV)
      RNA:Protein host interface. Cross-Link Assisted mRNP Purification (CLAMP)
      assessment reveals an extensive array of host/pathogen interactions centered on
      the viral RNAs (vRNAs). After prioritization of the host proteins associated with
      the vRNAs, we identified the site of Protein:vRNA interaction via a CLIP-seq
      approach and assessed the consequences of the RNA:protein binding event of hnRNP
      K, hnRNP I, and hnRNP M in regards to viral infection. Herein we demonstrate that
      mutation of the prioritized hnRNP:vRNA interaction sites effectively disrupted
      the hnRNP:vRNA interaction. Correlating with disrupted hnRNP:vRNA binding, SINV
      growth kinetics were reduced relative to wild type parental viral infections in a
      vertebrate and invertebrate tissue culture models of infection. The molecular
      mechanism leading to reduced viral growth kinetics were found to be dysregulated
      structural gene expression. Collectively, this study further defines the scope
      and importance of the alphavirus host/pathogen vRNA:protein
      interactions.IMPORTANCE Members of the genus Alphavirus are widely recognized for
      their potential to cause severe disease. Despite this recognition, there are no
      antiviral therapeutics, or safe and effective vaccines, currently available to
      treat alphaviral infection. Alphaviruses utilize the host cell machinery to
      efficiently establish and complete their viral lifecycle. However, the extent,
      and importance, of host/pathogen RNA:protein interactions is woefully under
      characterized. The efforts detailed in this study fulfill this critical gap; and
      the significance of this research is three-fold. First, the data presented here
      fundamentally expands the scope and understanding of alphavirus host/pathogen
      interactions. Secondly, this study identifies the site of interactions for
      several prioritized interactions and defines the contribution of the RNA:protein
      interaction at the molecular level. Finally, these studies build a strategy by
      which the importance of given host/pathogen interactions may be assessed, in the
      future, using a mouse model of infection.

PMID- 29321326
TI  - The Amino Terminus of Herpes Simplex Virus 1 Glycoprotein K (gK) Is Required for
      gB Binding to Akt, Release of Intracellular Calcium, and Fusion of the Viral
      Envelope with Plasma Membranes.
AB  - Previously, we have shown that the amino terminus of glycoprotein K (gK) binds to
      the amino terminus of gB and that deletion of the amino-terminal 38 amino acids
      of gK prevents herpes simplex virus 1 (HSV-1) infection of mouse trigeminal
      ganglia after ocular infection and virus entry into neuronal axons. Recently, it
      has been shown that gB binds to Akt during virus entry and induces Akt
      phosphorylation and intracellular calcium release. Proximity ligation and two-way
      immunoprecipitation assays using monoclonal antibodies against gB and Akt-1
      phosphorylated at S473 [Akt-1(S473)] confirmed that HSV-1(McKrae) gB interacted
      with Akt-1(S473) during virus entry into human neuroblastoma (SK-N-SH) cells and
      induced the release of intracellular calcium. In contrast, the gB specified by
      HSV-1(McKrae) gKDelta31-68, lacking the amino-terminal 38 amino acids of gK,
      failed to interact with Akt-1(S473) and induce intracellular calcium release. The
      Akt inhibitor miltefosine inhibited the entry of McKrae but not the gKDelta31-68
      mutant into SK-N-SH cells. Importantly, the entry of the gKDelta31-68 mutant but
      not McKrae into SK-N-SH cells treated with the endocytosis inhibitors pitstop-2
      and dynasore hydrate was significantly inhibited, indicating that McKrae
      gKDelta31-68 entered via endocytosis. These results suggest that the amino
      terminus of gK functions to regulate the fusion of the viral envelope with
      cellular plasma membranes.IMPORTANCE HSV-1 glycoprotein B (gB) functions in the
      fusion of the viral envelope with cellular membranes during virus entry. Herein,
      we show that a deletion in the amino terminus of glycoprotein K (gK) inhibits gB
      binding to Akt-1(S473), the release of intracellular calcium, and virus entry via
      fusion of the viral envelope with cellular plasma membranes.

PMID- 29321327
TI  - Human Papillomavirus 16 Infection Induces VAP-Dependent Endosomal Tubulation.
AB  - Human papillomavirus (HPV) infection involves complex interactions with the
      endocytic transport machinery, which ultimately facilitates the entry of the
      incoming viral genomes into the trans-Golgi network (TGN) and their subsequent
      nuclear entry during mitosis. The endosomal pathway is a highly dynamic
      intracellular transport system, which consists of vesicular compartments and
      tubular extensions, although it is currently unclear whether incoming viruses
      specifically alter the endocytic machinery. In this study, using MICAL-L1 as a
      marker for tubulating endosomes, we show that incoming HPV-16 virions induce a
      profound alteration in global levels of endocytic tubulation. In addition, we
      also show a critical requirement for the endoplasmic reticulum (ER)-anchored
      protein VAP in this process. VAP plays an essential role in actin nucleation and
      endosome-to-Golgi transport. Indeed, the loss of VAP results in a dramatic
      decrease in the level of endosomal tubulation induced by incoming HPV-16 virions.
      This is also accompanied by a marked reduction in virus infectivity. In VAP
      knockdown cells, we see that the defect in virus trafficking occurs after capsid
      disassembly but prior to localization at the trans-Golgi network, with the
      incoming virion-transduced DNA accumulating in Vps29/TGN46-positive hybrid
      vesicles. Taken together, these studies demonstrate that infection with HPV-16
      virions induces marked alterations of endocytic transport pathways, some of which
      are VAP dependent and required for the endosome-to-Golgi transport of the
      incoming viral L2/DNA complex.IMPORTANCE Human papillomavirus infectious entry
      involves multiple interactions with the endocytic transport machinery. In this
      study, we show that incoming HPV-16 virions induce a dramatic increase in
      endocytic tubulation. This tubulation requires ER-associated VAP, which plays a
      critical role in ensuring the delivery of cargoes from the endocytic compartments
      to the trans-Golgi network. Indeed, the loss of VAP blocks HPV infectious entry
      at a step after capsid uncoating but prior to localization at the trans-Golgi
      network. These results define a critical role for ER-associated VAP in endocytic
      tubulation and in HPV-16 infectious entry.

PMID- 29321328
TI  - Activities of Thrombin and Factor Xa Are Essential for Replication of Hepatitis E
      Virus and Are Possibly Implicated in ORF1 Polyprotein Processing.
AB  - Hepatitis E virus (HEV) is a clinically important positive-sense RNA virus. The
      ORF1 of HEV encodes a nonstructural polyprotein of 1,693 amino acids. It is not
      clear whether the ORF1 polyprotein (pORF1) is processed into distinct enzymatic
      domains. Many researchers have attempted to understand the mechanisms of pORF1
      processing. However, these studies gave various results and could never
      convincingly establish the mechanism of pORF1 processing. In this study, we
      demonstrated the possible role of thrombin and factor Xa in pORF1 processing. We
      observed that the HEV pORF1 polyprotein bears conserved cleavage sites of
      thrombin and factor Xa. Using a reverse genetics approach, we demonstrated that
      an HEV replicon having mutations in the cleavage sites of either thrombin or
      factor Xa could not replicate efficiently in cell culture. Further, we
      demonstrated in vitro processing when we incubated recombinant pORF1 fragments
      with thrombin, and we observed the processing of pORF1 polyprotein. The treatment
      of a liver cell line with a serine protease inhibitor as well as small
      interfering RNA (siRNA) knockdown of thrombin and factor Xa resulted in
      significant reduction in the replication of HEV. Thrombin and factor Xa have been
      well studied for their roles in blood clotting. Both of these proteins are
      believed to be present in the active form in the blood plasma. Interestingly, in
      this report, we demonstrated the presence of biologically active thrombin and
      factor Xa in a liver cell line. The results suggest that factor Xa and thrombin
      are essential for the replication of HEV and may be involved in pORF1 polyprotein
      processing of HEV.IMPORTANCE Hepatitis E virus (HEV) causes a liver disorder
      called hepatitis in humans, which is mostly an acute and self-limiting infection
      in adults. A high mortality rate of about 30% is observed in HEV-infected
      pregnant women in developing countries. There is no convincing opinion about HEV
      ORF1 polyprotein processing owing to the variability of study results obtained so
      far. HEV pORF1 has cleavage sites for two host cellular serine proteases,
      thrombin and factor Xa, that are conserved among HEV genotypes. For the first
      time, this study demonstrated that thrombin and factor Xa cleavage sites on HEV
      pORF1 are obligatory for HEV replication. Intracellular biochemical activities of
      the said serine proteases are also essential for efficient HEV replication in
      cell culture and must be involved in pORF1 processing. This study sheds light on
      the presence and roles of clotting factors with respect to virus replication in
      the cells.

PMID- 29321329
TI  - A Cyclin-Binding Motif in Human SAMHD1 Is Required for Its HIV-1 Restriction,
      dNTPase Activity, Tetramer Formation, and Efficient Phosphorylation.
AB  - Sterile alpha motif and HD domain-containing protein 1 (SAMHD1) regulates
      intracellular deoxynucleoside triphosphate (dNTP) levels and functions as a
      retroviral restriction factor through its dNTP triphosphohydrolase (dNTPase)
      activity. Human SAMHD1 interacts with cell cycle regulatory proteins cyclin A2,
      cyclin-dependent kinase 1 (CDK1), and CDK2. This interaction mediates
      phosphorylation of SAMHD1 at threonine 592 (T592), which negatively regulates HIV
      1 restriction. We previously reported that the interaction is mediated, at least
      in part, through a cyclin-binding motif (RXL, amino acids [aa] 451 to 453). To
      understand the role of the RXL motif in regulating SAMHD1 activity, we performed
      structural and functional analyses of RXL mutants and the effect on HIV-1
      restriction. We found that the RXL mutation (R451A and L453A, termed RL/AA)
      disrupted SAMHD1 tetramer formation and abolished its dNTPase activity in vitro
      and in cells. Compared to wild-type (WT) SAMHD1, the RL/AA mutant failed to
      restrict HIV-1 infection and had reduced binding to cyclin A2. WT SAMHD1 and
      RL/AA mutant proteins were degraded by Vpx from HIV-2 but were not spontaneously
      ubiquitinated in the absence of Vpx. Analysis of proteasomal and autophagy
      degradation revealed that WT and RL/AA SAMHD1 protein levels were enhanced only
      when both pathways of degradation were simultaneously inhibited. Our results
      demonstrate that the RXL motif of human SAMHD1 is required for its HIV-1
      restriction, tetramer formation, dNTPase activity, and efficient phosphorylation
      at T592. These findings identify a new functional domain of SAMHD1 important for
      its structural integrity, enzyme activity, phosphorylation, and HIV-1
      restriction.IMPORTANCE SAMHD1 is the first mammalian dNTPase identified as a
      restriction factor that inhibits HIV-1 replication by decreasing the
      intracellular dNTP pool in nondividing cells, although the critical mechanisms
      regulating SAMHD1 function remain unclear. We previously reported that mutations
      of a cyclin-binding RXL motif in human SAMHD1 significantly affect protein
      expression levels, half-life, nuclear localization, and phosphorylation,
      suggesting an important role of this motif in modulating SAMHD1 functions in
      cells. To further understand the significance and mechanisms of the RXL motif in
      regulating SAMHD1 activity, we performed structural and functional analyses of
      the RXL motif mutation and its effect on HIV-1 restriction. Our results indicate
      that the RXL motif is critical for tetramer formation, dNTPase activity, and HIV
      1 restriction. These findings help us understand SAMHD1 interactions with other
      host proteins and the mechanisms regulating SAMHD1 structure and functions in
      cells.

PMID- 29321330
TI  - Glycosyl-Phosphatidylinositol-Anchored Anti-HIV Env Single-Chain Variable
      Fragments Interfere with HIV-1 Env Processing and Viral Infectivity.
AB  - In previous studies, we demonstrated that single-chain variable fragments (scFvs)
      from anti-human immunodeficiency virus (HIV) Env monoclonal antibodies act as
      entry inhibitors when tethered to the surface of target cells by a glycosyl
      phosphatidylinositol (GPI) anchor. Interestingly, even if a virus escapes
      inhibition at entry, its replication is ultimately controlled. We hypothesized
      that in addition to functioning as entry inhibitors, anti-HIV GPI-scFvs may also
      interact with Env in an infected cell, thereby interfering with the infectivity
      of newly produced virions. Here, we show that expression of the anti-HIV Env GPI
      scFvs in virus-producing cells reduced the release of HIV from cells 5- to 22
      fold, and infectivity of the virions that were released was inhibited by 74% to
      99%. Additionally, anti-HIV Env GPI-scFv X5 inhibited virion production and
      infectivity after latency reactivation and blocked transmitter/founder virus
      production and infectivity in primary CD4+ T cells. In contrast, simian
      immunodeficiency virus (SIV) production and infectivity were not affected by the
      anti-HIV Env GPI-scFvs. Loss of infectivity of HIV was associated with a
      reduction in the amount of virion-associated Env gp120. Interestingly, an
      analysis of Env expression in cell lysates demonstrated that the anti-Env GPI
      scFvs interfered with processing of Env gp160 precursors in cells. These data
      indicate that GPI-scFvs can inhibit Env processing and function, thereby
      restricting production and infectivity of newly synthesized HIV. Anti-Env GPI
      scFvs therefore appear to be unique anti-HIV molecules as they derive their
      potent inhibitory activity by interfering with both early (receptor
      binding/entry) and late (Env processing and incorporation into virions) stages of
      the HIV life cycle.IMPORTANCE The restoration of immune function and persistence
      of CD4+ T cells in HIV-1-infected individuals without antiretroviral therapy
      requires a way to increase resistance of CD4+ T cells to infection by both R5-
      and X4-tropic HIV-1. Previously, we reported that anchoring anti-HIV-1 single
      chain variable fragments (scFvs) via glycosyl-phosphatidylinositol (GPI) to the
      surface of permissive cells conferred a high level of resistance to HIV-1
      variants at the level of entry. Here, we report that anti-HIV GPI-scFvs also
      derive their potent antiviral activity in part by blocking HIV production and Env
      processing, which consequently inhibits viral infectivity even in primary
      infection models. Thus, we conclude that GPI-anchored anti-HIV scFvs derive their
      potent blocking activity of HIV replication by interfering with successive stages
      of the viral life cycle. They may be effectively used in genetic intervention of
      HIV-1 infection.

PMID- 29321331
TI  - Germ Line IgM Is Sufficient, but Not Required, for Antibody-Mediated Alphavirus
      Clearance from the Central Nervous System.
AB  - Sindbis virus (SINV) infection of neurons in the brain and spinal cord in mice
      provides a model system for investigating recovery from encephalomyelitis and
      antibody-mediated clearance of virus from the central nervous system (CNS). To
      determine the roles of IgM and IgG in recovery, we compared the responses of
      immunoglobulin-deficient activation-induced adenosine deaminase-deficient (AID-/
      ), secretory IgM-deficient (sIgM-/-), and AID-/- sIgM-/- double-knockout (DKO)
      mice with those of wild-type (WT) C57BL/6 mice for disease, clearance of
      infectious virus and viral RNA from brain and spinal cord, antibody responses,
      and B cell infiltration into the CNS. Because AID is essential for immunoglobulin
      class switch recombination and somatic hypermutation, AID-/- mice produce only
      germ line IgM, while sIgM-/- mice secrete IgG but no IgM and DKO mice produce no
      secreted immunoglobulin. After intracerebral infection with the TE strain of
      SINV, most mice recovered. Development of neurologic disease occurred slightly
      later in sIgM-/- mice, but disease severity, weight loss, and survival were
      similar between the groups. AID-/- mice produced high levels of SINV-specific
      IgM, while sIgM-/- mice produced no IgM and high levels of IgG2a compared to WT
      mice. All mice cleared infectious virus from the spinal cord, but DKO mice failed
      to clear infectious virus from brain and had higher levels of viral RNA in the
      CNS late after infection. The numbers of infected cells and the amount of cell
      death in brain were comparable. We conclude that antibody is required and that
      either germ line IgM or IgG is sufficient for clearance of virus from the
      CNS.IMPORTANCE Mosquito-borne alphaviruses that infect neurons can cause fatal
      encephalomyelitis. Recovery requires a mechanism for the immune system to clear
      virus from infected neurons without harming the infected cells. Antiviral
      antibody has previously been shown to be a noncytolytic means for alphavirus
      clearance. Antibody-secreting cells enter the nervous system after infection and
      produce antiviral IgM before IgG. Clinical studies of human viral
      encephalomyelitis suggest that prompt production of IgM is associated with
      recovery, but it was not known whether IgM is effective for clearance. Our
      studies used mice deficient in production of IgM, IgG, or both to characterize
      the antibody necessary for alphavirus clearance. All mice developed similar signs
      of neurologic disease and recovered from infection. Antibody was necessary for
      virus clearance from the brain, and either early germ line IgM or IgG was
      sufficient. These studies support the clinical observation that prompt production
      of antiviral antibody is a determinant of outcome.

PMID- 29321332
TI  - ERK Is a Critical Regulator of JC Polyomavirus Infection.
AB  - The human JC polyomavirus (JCPyV) infects the majority of the population
      worldwide and presents as an asymptomatic, persistent infection in the kidneys.
      In individuals who are immunocompromised, JCPyV can become reactivated and cause
      a lytic infection in the central nervous system resulting in the fatal,
      demyelinating disease progressive multifocal leukoencephalopathy (PML). Infection
      is initiated by interactions between the capsid protein viral protein 1 (VP1) and
      the alpha2,6-linked sialic acid on lactoseries tetrasaccharide c (LSTc), while
      JCPyV internalization is facilitated by 5-hydroxytryptamine 2 receptors (5
      HT2Rs). The mechanisms by which the serotonin receptors mediate virus entry and
      the signaling cascades required to drive viral infection remain poorly
      understood. JCPyV was previously shown to induce phosphorylation of extracellular
      signal-regulated kinase (ERK), a downstream target of the mitogen-activated
      protein kinase (MAPK) pathway, upon virus entry. However, it remained unclear
      whether ERK activation was required for JCPyV infection. Both ERK-specific small
      interfering RNA (siRNA) and ERK inhibitor treatments resulted in significantly
      diminished JCPyV infection in both kidney and glial cells yet had no effect on
      the infectivity of the polyomavirus simian virus 40 (SV40). Experiments
      characterizing the role of ERK during steps in the viral life cycle indicate that
      ERK activation is required for viral transcription, as demonstrated by a
      significant reduction in production of large T antigen (TAg), a key viral protein
      associated with the initiation of viral transcription and viral replication.
      These findings delineate the role of the MAPK-ERK signaling pathway in JCPyV
      infection, elucidating how the virus reprograms the host cell to promote viral
      pathogenesis.IMPORTANCE Viral infection is dependent upon host cell factors,
      including the activation of cellular signaling pathways. These interactions
      between viruses and host cells are necessary for infection and play an important
      role in viral disease outcomes. The focus of this study was to determine how the
      human JC polyomavirus (JCPyV), a virus that resides in the kidney of the majority
      of the population and can cause the fatal, demyelinating disease progressive
      multifocal leukoencephalopathy (PML) in the brains of immunosuppressed
      individuals, usurps a cellular signaling pathway to promote its own infectious
      life cycle. We demonstrated that the activation of extracellular signal-regulated
      kinase (ERK), a component of the mitogen-activated protein kinase (MAPK) pathway,
      promotes JCPyV transcription, which is required for viral infection. Our findings
      demonstrate that the MAPK-ERK signaling pathway is a key determinant of JCPyV
      infection, elucidating new information regarding the signal reprogramming of host
      cells by a pathogenic virus.

PMID- 29321333
TI  - MicroRNA 130a Regulates both Hepatitis C Virus and Hepatitis B Virus Replication
      through a Central Metabolic Pathway.
AB  - Hepatitis C virus (HCV) infection has been shown to regulate microRNA 130a (miR
      130a) in patient biopsy specimens and in cultured cells. We sought to identify
      miR-130a target genes and to explore the mechanisms by which miR-130a regulates
      HCV and hepatitis B virus (HBV) replication. We used bioinformatics software,
      including miRanda, TargetScan, PITA, and RNAhybrid, to predict potential miR-130a
      target genes. miR-130a and its target genes were overexpressed or were knocked
      down by use of small interfering RNA (siRNA) or clustered regularly interspaced
      short palindromic repeat (CRISPR)/Cas9 guide RNA (gRNA). Selected gene mRNAs and
      their proteins, together with HCV replication in OR6 cells, HCV JFH1-infected
      Huh7.5.1 cells, and HCV JFH1-infected primary human hepatocytes (PHHs) and HBV
      replication in HepAD38 cells, HBV-infected NTCP-Huh7.5.1 cells, and HBV-infected
      PHHs, were measured by quantitative reverse transcription-PCR (qRT-PCR) and
      Western blotting, respectively. We selected 116 predicted target genes whose
      expression was related to viral pathogenesis or immunity for qPCR validation. Of
      these, the gene encoding pyruvate kinase in liver and red blood cell (PKLR) was
      confirmed to be regulated by miR-130a overexpression. miR-130a overexpression
      (via a mimic) knocked down PKLR mRNA and protein levels. A miR-130a inhibitor and
      gRNA increased PKLR expression, HCV replication, and HBV replication, while miR
      130a gRNA and PKLR overexpression increased HCV and HBV replication. Supplemental
      pyruvate increased HCV and HBV replication and rescued the inhibition of HCV and
      HBV replication by the miR-130a mimic and PKLR knockdown. We concluded that miR
      130a regulates HCV and HBV replication through its targeting of PKLR and
      subsequent pyruvate production. Our data provide novel insights into key
      metabolic enzymatic pathway steps regulated by miR-130a, including the steps
      involving PKLR and pyruvate, which are subverted by HCV and HBV
      replication.IMPORTANCE We identified that miR-130a regulates the target gene PKLR
      and its subsequent effect on pyruvate production. Pyruvate is a key intermediate
      in several metabolic pathways, and we identified that pyruvate plays a key role
      in regulation of HCV and HBV replication. This previously unrecognized, miRNA
      regulated antiviral mechanism has implications for the development of host
      directed strategies to interrupt the viral life cycle and prevent establishment
      of persistent infection for HCV, HBV, and potentially other viral infections.

PMID- 29321334
TI  - Mechanism of HIV-1 Resistance to an Electronically Constrained alpha-Helical
      Peptide Membrane Fusion Inhibitor.
AB  - SC29EK is an electronically constrained alpha-helical peptide HIV-1 fusion
      inhibitor that is highly effective against both wild-type and enfuvirtide (T20)
      resistant viruses. In this study, we focused on investigating the mechanism of
      HIV-1 resistance to SC29EK by two approaches. First, SC29EK-escaping HIV-1
      variants were selected and characterized. Three mutant viruses, which possessed
      two (N43K/E49A) or three (Q39R/N43K/N126K and N43K/E49A/N126K) amino acid
      substitutions in the N- and C-terminal repeat regions of gp41 were identified as
      conferring high resistance to SC29EK and cross-resistance to the first-generation
      (T20 and C34) and newly designed (sifuvirtide, MT-SC29EK, and 2P23) fusion
      inhibitors. The resistance mutations could reduce the binding stability of
      SC29EK, impair viral Env-mediated cell fusion and entry, and change the
      conformation of the gp41 core structure. Further, we determined the crystal
      structure of SC29EK in complex with a target mimic peptide, which revealed the
      critical intra- and interhelical interactions underlying the mode of action of
      SC29EK and the genetic pathway to HIV-1 resistance. Taken together, the present
      data provide new insights into the structure and function of gp41 and the
      structure-activity relationship (SAR) of viral fusion inhibitors.IMPORTANCE T20
      is the only membrane fusion inhibitor available for treatment of viral infection,
      but it has relatively low anti-HIV activity and genetic barriers for resistance,
      thus calling for new drugs blocking the viral fusion process. As an
      electronically constrained alpha-helical peptide, SC29EK is highly potent against
      both wild-type and T20-resistant HIV-1 strains. Here, we report the
      characterization of HIV-1 variants resistant to SC29EK and the crystal structure
      of SC29EK. The key mutations mediating high resistance to SC29EK and cross
      resistance to the first and new generations of fusion inhibitors as well as the
      underlying mechanisms were identified. The crystal structure of SC29EK bound to a
      target mimic peptide further revealed its action mode and genetic pathway to
      inducing resistance. Hence, our data have shed new lights on the mechanisms of
      HIV-1 fusion and its inhibition.

PMID- 29321335
TI  - Serum Hepatocyte Growth Factor Is Probably Associated With 3-Month Prognosis of
      Acute Ischemic Stroke.
AB  - BACKGROUND AND PURPOSE: Serum hepatocyte growth factor (HGF) is positively
      associated with poor prognosis of heart failure and myocardial infarction, and it
      can also predict the risk of ischemic stroke in population. The goal of this
      study was to investigate the association between serum HGF and prognosis of
      ischemic stroke. METHODS: A total of 3027 acute ischemic stroke patients were
      included in this post hoc analysis of the CATIS (China Antihypertensive Trial in
      Acute Ischemic Stroke). The primary outcome was composite outcome of death or
      major disability (modified Rankin Scale score >=3) within 3 months. RESULTS:
      After multivariate adjustment, elevated HGF levels were associated with an
      increased risk of primary outcome (odds ratio, 1.50; 95% confidence interval,
      1.10-2.03; Ptrend=0.015) when 2 extreme quartiles were compared. Each SD increase
      of log-transformed HGF was associated with 14% (95% confidence interval, 2%-27%)
      increased risk of primary outcome. Adding HGF quartiles to a model containing
      conventional risk factors improved the predictive power for primary outcome (net
      reclassification improvement: 17.50%, P<0.001; integrated discrimination index:
      0.23%, P=0.022). The association between serum HGF and primary outcome could be
      modified by heparin pre-treatment (Pinteraction=0.001), and a positive linear
      dose-response relationship between HGF and primary outcome was observed in
      patients without heparin pre-treatment (Plinearity<0.001) but not in those with
      heparin pre-treatment. CONCLUSIONS: Serum HGF levels were higher in the more
      severe stroke at baseline, and elevated HGF levels were probably associated with
      3-month poor prognosis independently of stroke severity among ischemic stroke
      patients, especially in those without heparin pre-treatment. Further studies from
      other samples of ischemic stroke patients are needed to validate our findings.

PMID- 29321336
TI  - Neuroimaging Identifies Patients Most Likely to Respond to a Restorative Stroke
      Therapy.
AB  - BACKGROUND AND PURPOSE: Patient heterogeneity reduces statistical power in
      clinical trials of restorative therapies. Valid predictors of treatment
      responsiveness are needed, and several have been studied with a focus on
      corticospinal tract (CST) injury. We studied performance of 4 such measures for
      predicting behavioral gains in response to motor training therapy. METHODS:
      Patients with subacute-chronic hemiparetic stroke (n=47) received standardized
      arm motor therapy, and change in arm Fugl-Meyer score was calculated from
      baseline to 1 month post-therapy. Injury measures calculated from baseline
      magnetic resonance imaging included (1) percent CST overlap with stroke, (2) CST
      related atrophy (cerebral peduncle area), (3) CST integrity (fractional
      anisotropy) in the cerebral peduncle, and (4) CST integrity in the posterior limb
      of internal capsule. RESULTS: Percent CST overlap with stroke, CST-related
      atrophy, and CST integrity did not correlate with one another, indicating that
      these 3 measures captured independent features of CST injury. Percent injury to
      CST significantly predicted treatment-related behavioral gains (r=-0.41;
      P=0.004). The other CST injury measures did not, neither did total infarct volume
      nor baseline behavioral deficits. When directly comparing patients with mild
      versus severe injury using the percent CST injury measure, the odds ratio was
      15.0 (95% confidence interval, 1.54-147; P<0.005) for deriving clinically
      important treatment-related gains. CONCLUSIONS: Percent CST injury is useful for
      predicting motor gains in response to therapy in the setting of subacute-chronic
      stroke. This measure can be used as an entry criterion or a stratifying variable
      in restorative stroke trials to increase statistical power, reduce sample size,
      and reduce the cost of such trials.

PMID- 29321337
TI  - Associations Between Collateral Status and Thrombus Characteristics and Their
      Impact in Anterior Circulation Stroke.
AB  - BACKGROUND AND PURPOSE: Thrombus characteristics and collateral score are
      associated with functional outcome in patients with acute ischemic stroke. It has
      been suggested that they affect each other. The aim of this study is to evaluate
      the association between clot burden score, thrombus perviousness, and collateral
      score and to determine whether collateral score influences the association of
      thrombus characteristics with functional outcome. METHODS: Patients with baseline
      thin-slice noncontrast computed tomography and computed tomographic angiography
      images from the MR CLEAN trial (Multicenter Randomized Clinical Trial of
      Endovascular Treatment of Acute Ischemic Stroke in the Netherlands) were included
      (n=195). Collateral score and clot burden scores were determined on baseline
      computed tomographic angiography. Thrombus attenuation increase was determined by
      comparing thrombus density on noncontrast computed tomography and computed
      tomographic angiography using a semiautomated method. The association of
      collateral score with clot burden score and thrombus attenuation increase was
      evaluated with linear regression. Mediation and effect modification analyses were
      used to assess the influence of collateral score on the association of clot
      burden score and thrombus attenuation increase with functional outcome. RESULTS:
      A higher clot burden score (B=0.063; 95% confidence interval, 0.008-0.118) and a
      higher thrombus attenuation increase (B=0.014; 95% confidence interval, 0.003
      0.026) were associated with higher collateral score. Collateral score mediated
      the association of clot burden score with functional outcome. The association
      between thrombus attenuation increase and functional outcome was modified by the
      collateral score, and this association was stronger in patients with moderate and
      good collaterals. CONCLUSIONS: Patients with lower thrombus burden and higher
      thrombus perviousness scores had higher collateral score. The positive effect of
      thrombus perviousness on clinical outcome was only present in patients with
      moderate and high collateral scores. CLINICAL TRIAL REGISTRATION: URL:
      http://www.trialregister.nl. Unique identifier: NTR1804 and URL:
      http://www.controlled-trials.com Unique identifier: ISRCTN10888758.

PMID- 29321339
TI  - Detection of Anterior Circulation Large Artery Occlusion in Ischemic Stroke Using
      Noninvasive Cerebral Oximetry.
AB  - BACKGROUND AND PURPOSE: Large artery occlusion (LAO) in ischemic stroke requires
      recognition and triage to an endovascular stroke treatment center. Noninvasive
      LAO detection is needed to improve triage. METHODS: Prospective study to test
      whether noninvasive cerebral oximetry can detect anterior circulation LAO in
      acute stroke. Interhemispheric DeltaBrSO2 in LAO was compared with controls.
      RESULTS: In LAO stroke, mean interhemispheric DeltaBrSO2 was -8.3+/-5.8% (n=19),
      compared with 0.4+/-5.8% in small artery stroke (n=17), 0.4+/-6.0% in hemorrhagic
      stroke (n=14), and 0.2+/-7.5% in subjects without stroke (n=19) (P<0.001).
      Endovascular stroke treatment reduced the DeltaBrSO2 in most LAO subjects
      (16/19). Discrimination of LAO at a -3% DeltaBrSO2 cut had 84% sensitivity and
      70% specificity. Addition of the G-FAST clinical score (gaze-face-arm-speech-
      time) to the BrSO2 measure had 84% sensitivity and 90% specificity. CONCLUSIONS:
      Noninvasive cerebral oximetry may help detect LAO in ischemic stroke,
      particularly when combined with a simple clinical scoring system.

PMID- 29321338
TI  - Improving Access to Thrombolysis and Inhospital Management Times in Ischemic
      Stroke: A Stepped-Wedge Randomized Trial.
AB  - BACKGROUND AND PURPOSE: A suboptimal number of ischemic stroke patients eligible
      for thrombolysis actually receive it, partly because of extended inhospital
      delays. We developed a comprehensive program designed for emergency unit staff
      and evaluated its effectiveness for reducing intrahospital times and improving
      access to thrombolysis. METHODS: We conducted a randomized stepped-wedge
      controlled trial in 18 emergency unit. The sequentially implemented training
      intervention, targeting emergency physicians and nurses, was based on
      specifically designed videos and interactive simulation workshops on
      intrahospital management optimization. The effectiveness was assessed on
      intrahospital times and thrombolysis proportion. During the study period, all
      consecutive patients with confirmed ischemic stroke and no contraindications to
      thrombolysis were included. RESULTS: A total of 328 patients were enrolled in the
      control group and 363 in the intervention group. Mean age was 73.6 years. Overall
      thrombolysis proportion was 34.2% in the intervention group versus 25.6% in the
      control group (adjusted odds ratio, 1.42; 95% confidence interval, 1.01-2.01),
      thrombolysis proportion within 4 hours 30 minutes almost doubled (adjusted odds
      ratio, 1.9; 95% confidence interval, 1.32-2.73). Although imaging-to-stroke unit
      time was significantly decreased in the intervention group (39 versus 53 minutes;
      P=0.03), median door-to-imaging and door-to-needle times were not different
      between groups (P=0.70 and P=0.40, respectively). CONCLUSIONS: An interactive and
      multifaceted training program targeting emergency professionals was significantly
      associated with an increased access to thrombolysis, especially within 4 hours
      and 30 minutes. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov.
      Unique identifier: NCT02814760.

PMID- 29321340
TI  - Retrospective Methods Analysis of Semiautomated Intracerebral Hemorrhage Volume
      Quantification From a Selection of the STICH II Cohort (Early Surgery Versus
      Initial Conservative Treatment in Patients With Spontaneous Supratentorial Lobar
      Intracerebral Haematomas).
AB  - BACKGROUND AND PURPOSE: The ABC/2 method for calculating intracerebral hemorrhage
      (ICH) volume has been well validated. However, the formula, derived from the
      volume of an ellipse, assumes the shape of ICH is elliptical. We sought to
      compare the agreement of the ABC/2 formula with other methods through
      retrospective analysis of a selection of the STICH II cohort (Early Surgery
      Versus Initial Conservative Treatment in Patients With Spontaneous Supratentorial
      Lobar Intracerebral Haematomas). METHODS: From 390 patients, 739 scans were
      selected from the STICH II image archive based on the availability of a CT scan
      compatible with OsiriX DICOM viewer. ICH volumes were calculated by the reference
      standard semiautomatic segmentation in OsiriX software and compared with
      calculated arithmetic methods (ABC/2, ABC/2.4, ABC/3, and 2/3SC) volumes. Volumes
      were compared by difference plots for specific groups: randomization ICH (n=374),
      3- to 7-day postsurgical ICH (n=206), antithrombotic-associated ICH (n=79),
      irregular-shape ICH (n=703) and irregular-density ICH (n=650). Density and shape
      were measured by the Barras ordinal shape and density groups (1-5). RESULTS: The
      ABC/2.4 method had the closest agreement to the semiautomatic segmentation volume
      in all groups, except for the 3- to 7-day postsurgical ICH group where the ABC/3
      method was superior. CONCLUSIONS: Although the ABC/2 formula for calculating
      elliptical ICH is well validated, it must be used with caution in ICH scans where
      the elliptical shape of ICH is a false assumption. We validated the adjustment of
      the ABC/2.4 method in randomization, antithrombotic-associated, heterogeneous
      density, and irregular-shape ICH. CLINICAL TRIAL REGISTRATION: URL:
      http://www.isrctn.com/ISRCTN22153967. Unique identifier: ISRCTN22153967.

PMID- 29321341
TI  - Exercise tolerance and balance of inspiratory-to-expiratory muscle strength in
      relation to breathing timing in patients with chronic obstructive pulmonary
      disease.
AB  - RATIONALE: Little is known about the applicability of respiratory muscle training
      based on exertional pathophysiological conditions in patients with chronic
      obstructive pulmonary disease (COPD). The aim of this study was to investigate
      the relationship between breathing timing and exertional responses, as well as
      whether exertional changes in the inspiratory duty cycle (Ti/Ttot) affect
      pathophysiological conditions, including respiratory muscles. METHODS: Forty-five
      stable COPD patients (mean age: 71.2 years, severe and very severe COPD: 80%)
      were evaluated based on exertional cardiopulmonary function and respiratory
      muscle strength. To compare exertional responses and the balance of inspiratory
      to-expiratory muscle strength, the patients were divided into two groups
      according to whether the Ti/Ttot increased (Ti/Ttot-increased group: resting
      Ti/Ttot <= peak Ti/Ttot, n = 21) or decreased during exercise (Ti/Ttot-decreased
      group: resting Ti/Ttot > peak Ti/Ttot, n = 24). RESULTS: At peak exercise, the
      Ti/Ttot was positively correlated with minute ventilation ([Formula: see text]
      E), and oxygen uptake ([Formula: see text]) in all patients. No significant
      differences were seen in breathing frequency, tidal volume, or [Formula: see
      text] E at peak exercise between the two groups. Compared with the Ti/Ttot
      increased group, the Ti/Ttot-decreased group had significantly lower mean values
      of [Formula: see text] and DeltaFO2 (the inspired minus expired oxygen
      concentration) at peak exercise, and significantly higher mean values of the
      absolute ratio of maximal inspiratory pressure/maximal expiratory pressure.
      CONCLUSIONS: The exertional change of breathing timing affected exercise
      tolerance and the balance of inspiratory-to-expiratory muscle strength; this
      finding might be helpful in making the contradictory choice of managing COPD
      patients with inspiratory or expiratory muscle training.

PMID- 29321342
TI  - Association between SSR markers and fibre traits in sea island cotton (Gossypium
      barbadense) germplasm resources.
AB  - Identification of molecular markers associated with fibre traits can accelerate
      cotton marker-assisted selection (MAS) programmes. In this study, Gossypium
      barbadense germplasm accessions with diverse origins (n = 123) were used to
      perform association analysis of fibre traits with 120 polymorphic simple sequence
      repeat (SSR) markers. In total, 120 polymorphic primer pairs amplified 258 loci
      with a mean of 2.15 loci per primer. Population structure analysis identified
      three main clusters for the accessions, which indicated agreement of genetic and
      predefined populations. Marker-trait associations (n = 58) were detected for 10
      fibre traits with 26 SSR markers located on 15 chromosomes. The R2 (phenotypic
      variation explained) ranged from 3.19 to 15.21%. Two markers (NAU5465 and
      NAU3013) were found to be stably associated with boll number per plant (BNP) and
      fibre uniformity (UI), respectively. Four markers (BNL252, NAU3424,NAU3324 and
      CGR5202) associated with fibre quality traits preferentially clustered on the D8
      chromosome, which was thus identified as an important candidate region for study
      molecular mechanisms underlying fibre quality and for use in breeding cotton
      cultivars for improving fibre quality. This study generated molecular data with a
      potential for better understanding of the genetic basis of the fibre traits and
      provided new markers for MAS in G. barbadense breeding programmes.

PMID- 29321343
TI  - Population genetic diversity of marble goby (Oxyeleotris marmoratus) inferred
      from mitochondrial DNA and microsatellite analysis.

PMID- 29321344
TI  - A genetic variant in COL11A1 is functionally associated with lumbar disc
      herniation in Chinese population.
AB  - This study aimed to explore whether the genetic variant of COL11A1 is
      functionally associated with the development of lumbar disc herniation (LDH) in
      Chinese population. SNP rs1676486 of COL11A1 was genotyped in 647 patients and
      532 healthy controls. The differences of genotype and allele distributions
      between LDH patients and healthy controls were evaluated using the chi2 test. One
      way ANOVA test was used to compare the relationship between genotypes and
      clinical features including tissue expression of COL11A1 and the degree of disc
      degeneration. Patients were found to have a significantly higher frequency of TT
      than the controls (10.2% versus 7.3%, P = 0.004). Besides, the frequency of
      allele T was found to be remarkably higher in the patients than the controls
      (34.8% versus 28.1%, P < 0.001) with an odds ratio of 1.36 (95% confidential
      interval=1.14-1.63). Patients with genotype TT were found to have remarkably more
      severe disc degeneration (P = 0.02). Besides, the expression of COL11A1 in the
      lumbar disc was significantly lower in the patients with genotype TT than in
      those with genotype CT or CC (P < 0.001). Moreover, the expression level was
      inversely correlated with the severity of disc degeneration (P < 0.001). We
      confirmed that the rs1676486 of COL11A may be functionally associated with LDH in
      the Chinese population. Extracellular matrix related proteins may play an
      important role in the pathogenesis of LDH. Our findings shed light on a better
      understanding of the pathogenesis of LDH, which could be a promising target for a
      novel treatment modality of LDH.

PMID- 29321345
TI  - Genetic variability and structure of an isolated population of Ambystoma
      altamirani, a mole salamander that lives in the mountains of one of the largest
      urban areas in the world.
AB  - Amphibians are globally threatened by habitat loss and fragmentation; species
      within the order Ambystoma are not the exception, as there are 18 species of mole
      salamanders in Mexico, of which 16 are endemic and all species are under some
      national or international status of protection. The mole salamander, Ambystoma
      altamirani is a microendemic species, which is distributed in central Mexico,
      within the trans-Mexican volcanic belt, and is one of the most threatened species
      due to habitat destruction and the introduction of exotic species. Nine
      microsatellite markers were used to determine the genetic structure, genetic
      variability, effective population size, presence of bottlenecks and inbreeding
      coefficient of one population of A. altamirani to generate information which
      might help to protect and conserve this threatened species. We found two genetic
      subpopulations with significant level of genetic structure (FST = 0.005) and high
      levels of genetic variability (Ho = 0.883; He = 0.621); we also found a small
      population size (Ne = 8.8), the presence of historical (M = 0.486) and recent
      bottlenecks under IAM and TPM models, with a low, but significant coefficient of
      inbreeding (FIS = -0.451). This information will help us to raise conservation
      strategies of this microendemic mole salamander species.

PMID- 29321346
TI  - Mutational screening of PKD2 gene in the north Indian polycystic kidney disease
      patients revealed 28 genetic variations.
AB  - Polycystic kidney disease (PKD) is a systemic disorder which adds majority of
      renal patients to end stage renal disease. Autosomal dominant polycystic kidney
      disease (ADPKD) is more prevalent and leading cause of dialysis and kidney
      transplant. Linkage analysis revealed some closely linked loci, two of which are
      identified as PKD1, PKD2 and an unidentified locus to ADPKD. This study was
      performed using PCR and automated DNA sequencing in 84 cases and 80 controls to
      test potential candidature of PKD2 as underlying cause of PKD by in silico and
      statistical analyses. Two associated symptoms, hypertension (19%) and liver cyst
      (31%) havemajor contribution to PKD. Gender-based analysis revealed that familial
      female patients (27%) and familialmale patients (33%) are more hypertensive.
      Liver cyst, the second major contributing symptom presented by large percentage
      of sporadic males (46%). Genetic screening of all 15 exons of PKD2 revealed eight
      pathogenic (c.854_854delG, c.915C>A, c.973C>T, c.1050_1050delC, c.1604_1604delT,
      c.1790T>C, c.2182_2183delAG, c.2224C>T) and eight likely pathogenic (g.11732A>G,
      c.646T>C, c.1354A>G, g.39212G>C, c.1789C>A, c.1849C>A, c.2164G>T, c.2494A>G)DNA
      sequence variants. In our study, 27.38% (23/84) cases shown pathogenic / likely
      pathogenic variants in PKD2 gene. Some regions of PKD2 prone for genetic
      variation suggested to be linked with disease pathogenesis. This noticeable hot
      spot regions hold higher frequency (50%) of pathogenic / likely pathogenic
      genetic variants constituting single nucleotide variants than large deletion and
      insertion that actually represents only 41.08% of coding sequence of PKD2.
      Statistically significant association for IVS3-22AA genotype was observed with
      PKD, while association of IVS4+62C>T was found insignificant.

PMID- 29321347
TI  - Identification of housekeeping genes as references for quantitative real-time RT
      PCR analysis in Misgurnus anguillicaudatus.
AB  - Quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR)
      is a well-known method to quantify gene expression by comparing with the
      reference genes. Generally, housekeeping genes were set as references, as for
      their stable expression in varying conditions. Here, we try to evaluate few of
      such genes to identify suitable housekeeping genes as references for qRT-PCR
      analysis of gene expression in Misgurnus anguillicaudatus. This study evaluated
      the expression of four commonly used housekeeping genes, i.e. b-actin (ACTB),
      elongation factor 1 alpha (EF-1a), glyceraldehyde-3-phosphate (GAPDH) and 18S
      ribosomal RNA (18S rRNA), in gender difference, effects of tissue type, different
      developmental stages, chemical treatment of embryos/larvae with commonly used
      vehicles for administration and agents that represent known environmental
      toxicant. Rank ordering of expression stability was done using geNorm, NormFinder
      and BestKeeper algorithms. Results suggested that in the qRTPCR test, in all the
      experimental conditions, EF-1a could be selected as reference gene when analysing
      a target gene. For the study of different development stages, ACTB could be a
      candidate as reference gene. For the studies associated with different gender and
      tissue types, EF-1a would be better targeted as reference gene. Meanwhile, in
      toxicant treatment, expression of EF-1a seems to be more stable than others and
      could be considered as reference gene. This study could provide useful guidelines
      that can be expected to aid M. anguillicaudatus researchers in their initial
      choice of housekeeping genes for future studies and enable more accurate
      normalization of gene expression data.

PMID- 29321348
TI  - Influence of thiopurine methyltransferase gene polymorphism on Egyptian children
      with acute lymphoblastic leukaemia.
AB  - Thiopurine methyltransferase (TPMT) gene polymorphism regulates thiopurine
      therapeutic efficacy and toxicity. The aim of this study was to determine the
      influence of TPMT gene polymorphism in Egyptian children with acute lymphoblastic
      leukaemia (ALL). Sixty-four patients with ALL, T lineage (27%) and pre-B
      phenotype (73%), who were treated with BFM 90 or CCG 1991 standard risk protocol,
      and who also experiencedmyleosuppresion toxicity and required interruption
      and/ormodification of thiopurine chemotherapy were recruited over a year period.
      Thirty-two patients were on maintenance and another 32 completed their
      chemotherapy. Seventy healthy age-matched and sex-matched children served as
      controls. They were subjected to clinical assessment, haematological panel
      investigations and TPMT gene polymorphism for G238C, G460A and A719G alleles
      assessment using PCRfollowed byRFLP analysis.Although none of the studied
      patients had themutantTPMTvariant alleles,myelosuppression toxicity in the form
      of different degree of neutropenia was detected in all patients. As a result of
      myelosuppression toxicity, most of the patients needed 6-MP dose modification
      either once (53.1%), twice (15.6%), or >= thrice (25.1%) during their maintenance
      course and 96.9% of the patients required to stop 6-MP for less than a week
      (62.5%), up to 2 weeks (28.1%), or > 2 weeks (6.3%). Patients also developed
      infection who mostly (71%) needed hospitalization. None of the studied G238C,
      G460A and A719G TPMT variant alleles were detected. Infections and febrile
      neutropenia were common causes of 6-PM dose modification and interruption.

PMID- 29321349
TI  - Analysis of two susceptibility SNPs in HLA region and evidence of interaction
      between rs6457617 in HLA-DQB1 and HLA-DRB1*04 locus on Tunisian rheumatoid
      arthritis.
AB  - Previous genomewide association studies (GWAS) and meta-analyses have enumerated
      several genes/loci in major histocompatibility complex region, which are
      consistently associated with rheumatoid arthritis (RA) in different ethnic
      populations. Given the genetic heterogeneity of the disease, it is necessary to
      replicate these susceptibility loci in other populations. In this case, we
      investigate the analysis of two SNPs, rs13192471 and rs6457617, from the human
      leukocyte antigen (HLA) region with the risk of RA in Tunisian population. These
      SNPs were previously identified to have a strong RA association signal in several
      GWAS studies. A case-control sample composed of 142 RA patients and 123 healthy
      controls was analysed. Genotyping of rs13192471 and rs6457617 was carried out
      using real-time PCR methods by TaqMan allelic discrimination assay. A trend of
      significant association was found in rs6457617 TT genotype with susceptibility to
      RA (P = 0.04, pc = 0.08, OR = 1.73). Moreover, using multivariable analysis, the
      combination of rs6457617*TT-HLA-DRB1*04+ increased risk of RA (OR = 2.38), which
      suggest a gene-gene interaction event between rs6457617 located within the HLA
      DQB1 and HLA-DRB1. Additionally, haplotypic analysis highlighted a significant
      association of rs6457617*T-HLA-DRB1*04+ haplotype with susceptibility to RA (P =
      0.018, pc = 0.036, OR = 1.72). An evidence of association was shown subsequently
      in antiCCP+ subgroup with rs6457617 both in T allele and TT genotype (P = 0.01,
      pc = 0.03, OR = 1.66 and P = 0.008, pc = 0.024, OR = 1.28, respectively).
      However, no association was shown for rs13192471 polymorphism with susceptibility
      and severity to RA. This study suggests the involvement of rs6457617 locus as
      risk variant for susceptibility/severity to RA in Tunisian population. Secondly,
      it highlights the gene-gene interaction between HLA-DQB1 and HLA-DRB1.

PMID- 29321350
TI  - Neuro-fuzzy model of homocysteine metabolism.
AB  - In view of well-documented association of hyperhomocysteinaemia with a wide
      spectrum of diseases and higher incidence of vitamin deficiencies in Indians, we
      proposed a mathematical model to forecast the role of demographic and genetic
      variables in influencing homocysteinemetabolism and investigated the influence of
      life style modulations in controlling homocysteine levels. Total plasma
      homocysteine levels were measured in fasting samples using reverse phase HPLC.
      Multiple linear regression (MLR) and neuro-fuzzy models were developed. The MLR
      model explained 64% variability in homocysteine, while the neurofuzzy model
      showed higher accuracy in predicting homocysteine with a mean absolute error of
      0.00002 MUmol/L. Methylene tetrahydrofolate reductase (MTHFR) C677T, 5
      methyltetrahydrofolate homocysteine methyltransferase (MTR) A2756G and 5-
      methyltetrahydrofolate homocysteine methyltransferase reductase (MTRR) A66G were
      shown to be positively associatiated with homocysteine, while nonvegetarian diet,
      serine hydroxymethyltransferase 1 (SHMT1) C1420T and TYMS 5'-UTR 28 bp tandem
      repeat exhibited negative association with homocysteine. The protective role of
      SHMT1 C1420T was attributed to more H-bonding interactions in the mutant modelled
      compared to the wild type, as shown through in silico analysis. To conclude,
      polymorphisms in genes regulating remethylation of homocysteine strongly
      influence homocysteine levels. The restoration of one-carbon homeostasis by SHMT1
      C1420T or increased flux of folate towards remethylation due to TYMS 5'-UTR 28 bp
      tandem repeat or nonvegetarian diet can lower homocysteine levels.

PMID- 29321351
TI  - Glutathione S-transferase P1 gene polymorphisms and susceptibility to coronary
      artery disease in a subgroup of north Indian population.
AB  - The present study aimed to investigate the association of g.313A>G and g.341C>T
      polymorphisms of GSTP1 with coronary artery disease (CAD) in a subgroup of north
      Indian population. In the present case-control study, CAD patients (n = 200) and
      age-matched, sex-matched and ethnicity-matched healthy controls (n = 200) were
      genotyped for polymorphisms in GSTP1 using polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP) method. Genotype distribution of
      g.313A>Gand g.341C>T polymorphisms of GSTP1 gene was significantly different
      between cases and controls (P = 0.005 and 0.024, respectively). Binary logistic
      regression analysis showed significant association of A/G (odds ratio (OR): 1.6,
      95% CI: 1.08-2.49, P = 0.020) and G/G (OR: 3.1, 95% CI: 1.41-6.71, P = 0.005)
      genotypes of GSTP1 g.313A>G, and C/T (OR: 5.8, 95% CI: 1.26-26.34, P = 0.024)
      genotype of GSTP1 g.341C>T with CAD. The A/G and G/G genotypes of g.313A>G and
      C/T genotype of g.341C>T conferred 6.5-fold increased risk for CAD (OR: 6.5, 95%
      CI: 1.37-31.27, P = 0.018).Moreover, the recessive model of GSTP1 g.313A>G is the
      best fit inheritance model to predict the susceptible gene effect (OR: 2.3, 95%
      CI: 1.11-4.92, P = 0.020). In conclusion, statistically significant associations
      of GSTP1 g.313A>G (A/G, G/G) and g.341C>T (C/T) genotypes with CAD were observed.

PMID- 29321352
TI  - Genetic analysis of 55 northern Vietnamese patients with Wilson disease: seven
      novel mutations in ATP7B.
AB  - Wilson disease (WD) is an autosomal recessive disorder of copper metabolism. The
      gene responsible for WD was discovered in 1993 and is located on chromosome 13 at
      13q14.3. It encodes a copper-specific transporting P-type ATPase. Early diagnosis
      can improve treatment outcome and decrease the rate of disability or even
      mortality.We used Sanger sequencing to identify mutation hot spots in 55 northern
      Vietnamese with a clinical diagnosis of WD. Mutations were screened and detected
      by direct DNA sequencing. A total of 26 different ATP7B gene mutations were
      identified, including seven novel mutations (five nonsense and two missense
      mutations). The most frequent mutations were p.Ser105Ter (24.55%), p.Arg778Leu
      (5.45%) and p.Thr850Ile (4.55%). Mutation detection rate in exon 2 was 34.55% and
      ranked first, followed by exon 8 with 16.36%, and exon 18 with 10.91% each, thus,
      exons 2, 8 and 18 are the mutation hot spots for northern VietnameseWD patients.
      These findings were different from previous studies in Asia. Our research
      established a suitable strategy for ATP7B gene testing in northern Vietnamese WD
      patients.

PMID- 29321353
TI  - Identification and association of novel lncRNA pouMU1 gene mutations with chicken
      performance traits.
AB  - The biological functions of long noncoding RNAs (lncRNAs), which play an
      important role in regulating development and gene expression, may be affected by
      variations in lncRNA gene loci or associated genomic sequences. However, the
      functions of many lncRNAs remain unknown. To analyse correlations between
      mutations in pouMU1 with chicken growth and carcass traits, 860 chickens from a
      Gushi*Anka F2 resource population and 96 Lushi, Xichuan, Changshun and recessive
      white chickens were used to evaluate the genetic effect of the pouMU1 gene. We
      performed quantitative real-time polymerase chain reaction (qRT-PCR) to analyse
      the relative expression levels of pouMU1 in nine different tissues and stages of
      development. pouMU1 expression was highest in pectoralis and leg muscles, whereas
      no expression was observed in the heart, liver and abdominal fat. Using direct
      sequencing and polymerase chain reaction-restriction fragment length polymorphism
      (PCR-RFLP) methods, two novel sequence mutations (g.1198A>G and g.1238
      1239del/insGA) were detected in the pouMU1 gene. SPSS software was used for
      statistical analysis in association studies. Based on the association data, the
      presence of both variants was significantly associated with leg muscle fibre
      width and leg muscle fibre roundness (P < 0.05) and highly associated with leg
      muscle fibre girth and body weight at 0 week of age (P < 0.01). These data
      suggest that pouMU1 might participate in regulating chicken muscle development
      and growth, and the findings offer new insight into the functions of sequence
      mutations in lncRNAs.

PMID- 29321354
TI  - Marker-assisted pyramiding of Thinopyrum-derived leaf rust resistance genes Lr19
      and Lr24 in bread wheat variety HD2733.
AB  - This study was undertaken to pyramid two effective leaf rust resistance genes
      (Lr19 and Lr24) derived from Thinopyrum (syn. Agropyron), in the susceptible, but
      agronomically superior wheat cultivar HD2733 using marker-assisted selection. In
      the year 2001, HD2733 was released for irrigated timely sown conditions of the
      north eastern plains zone (NEPZ) of India became susceptible to leaf rust, a
      major disease of the region. Background selection helped in developing near
      isogenic lines (NILs) of HD2733 with Lr19 and Lr24 with 97.27 and 98.94%,
      respectively, of genomic similarity with the parent cultivar, after two
      backcrossing and one generation of selfing.NILs were intercrossed to combine the
      genes Lr19 and Lr24. The combination of these two genes in the cultivar HD2733 is
      expected to provide durable leaf rust resistance in farmers' fields.

PMID- 29321355
TI  - Genetic diversity, phylogeographic structure and effect of selection at the
      mitochondrial hypervariable region of Nigerian chicken populations.
AB  - In this study, the maternal genetic diversity, phylogenetic relationship and
      effect of natural selection on indigenous chickens from Nigeria were assessed. A
      total of 397-bp fragment of the mitochondrial DNA (mtDNA) D-loop region of 171
      indigenous chickens from four populations of Nigeria and four commercial egg line
      strains (two Anak titan, one Giriraja and one Yaffa) as out-groups were analysed.
      Thirty-one haplotypes (28 from Nigerian chickens and three from commercial
      strains) and 34 polymorphic sites were identified. The mean haplotypic and
      nucleotide diversity were found to be 0.39 +/- 0.05 and 0.02 +/- 0.02,
      respectively. Majority of Nigerian chicken haplotypes observed were grouped into
      haplogroup D which originated from Indian subcontinent, suggesting a single
      maternal lineage. Genetic variation within and between populations accounted for
      97.30 and 2.70% of the total genetic variation, respectively, which is in
      agreement with a recent and maternal founding effect. High number (4) of
      negatively selected sites observed based on single likelihood ancestral counting
      (SLAC) model indicated that the sampled Nigerian chicken populations were
      undergoing purifying selection. This study concluded that there was relatively
      high genetic diversity and differentiation, thus, this information will probably
      paveway for further evaluation studies, preservation and improvement of Nigerian
      chickens as genetic resources towards ensuring food security.

PMID- 29321357
TI  - Mapping of Id locus for dermal shank melanin in a Chinese indigenous chicken
      breed.
AB  - The dermal shank pigmentation, one of the defining traits of chicken breeds, is
      caused by an abnormal deposition of melanin in the dermis of the shank. The
      abnormal deposition is controlled by the sex-linked inhibitor of dermal melanin
      (Id). In this study, we aim to locate the gene responsible for the dermal shank
      pigmentation in chickens by an association analysis and a differential expression
      analysis. Based on our results, 72 single-nucleotide polymorphisms (SNPs) located
      in Z chromosome (chrZ): 71-73 Mb (galGal3) were selected to further explore their
      relationships with the dermal shank pigmentation in pure lines of 96 Gushi hens
      and 96 Gushi hens with a yellow shank skin colour. The results of the association
      analysis showed that the SNPs located in chrZ: 72.58-72.99 Mb (galGal3) (chrZ:
      79.02-79.44 Mb (galGal4)) are significantly associated with the dermal shank
      pigmentation. Based on the results of our previous studies and the present
      association analysis, the zinc-finger protein 608 (ZNF608), GRAM domain
      containing 3 (GRAMD3), aldehyde dehydrogenase 7 family member A1 (ALDH7A1), fem-1
      homologue C (FEM1C), beta-1,4-galactosyltransferase 1 (B4GALT1) and versican
      (VCAN) genes were selected for the differential expression analysis. The gene
      expression profiles showed that the expression of GRAMD3 gene in the dermis
      tissues of the shank was significantly (P = 0.010738 < 0.05) higher in 350-day
      old Gushi chickens characterized by the dermal shank pigmentation than in one-day
      old Gushi chickens. The dermal shank pigmentation was not present in the one-day
      old Gushi chickens. Additionally, the results of the association analysis and the
      expression analysis showed that GRAMD3 could be the most likely candidate gene
      for the Id locus. However, we did not detect a mutation, i.e. significantly
      associated with this trait within GRAMD3. Therefore, we concluded that the
      variations located in the flanking region of GRAMD3 led to the abnormal
      expression of GRAMD3, which requires further study.

PMID- 29321356
TI  - The connexin 46 mutant (V44M) impairs gap junction function causing congenital
      cataract.
AB  - Connexin 46 (Cx46) is important for gap junction channels formation which plays
      crucial role in the preservation of lens homeostasis and transparency.
      Previously, we have identified a missense mutation (p.V44M) of Cx46 in a
      congenital cataract family. This study aims at dissecting the potential
      pathogenesis of the causative mutant of cataract. Plasmids carrying wild-type
      (wt) and mutant (V44M) of Cx46 were constructed and expressed in Hela cells
      respectively.Western blotting and fluorescence microscopy were applied to analyse
      the expression and subcellular localization of recombinant proteins,
      respectively. Scrape loading dye transfer experiment was performed to detect the
      transfer capability of gap junction channels among cells expressed V44Mmutant.
      The results demonstrated that in transfected Hela cells, both wt-Cx46 and Cx46
      V44M were localized abundantly in the plasma membrane. No significant difference
      was found between the protein expressions of the two types of Cx46. The
      fluorescent localization assay revealed the plaque formation, significantly
      reduced in the cells expressing Cx46 V44M. Immunoblotting analysis demonstrated
      that formation of Triton X-100 insoluble complex decreased obviously in mutant
      Cx46. Additionally, the scrape-loading dye-transfer experiment showed a lower dye
      diffusion distance of Cx46 V44M cells, which indicates that the gap junction
      intercellular communication activity was aberrant. Human Cx46 V44M mutant causing
      cataracts result in abnormally decreased formation of gap junction plaques and
      impaired gap junction channel function.

PMID- 29321358
TI  - Genetic variants influencing lipid levels and risk of dyslipidemia in Chinese
      population.
AB  - Recently, several human genetic and genomewide association studies (GWAS) have
      discovered many genetic loci that are associated with the concentration of the
      blood lipids. To confirm the reported loci in Chinese population, we conducted a
      crosssection study to analyse the association of 25 reported SNPs, genotyped by
      the ABI SNaPshot method, with the blood levels of total cholesterol (TC), low
      density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol
      (HDL-C) and triglycerides (TG) in 1900 individuals by multivariate analysis.
      Logistic regression was applied to assess the association of the genetic loci
      with the risk of different types of dyslipidemia. Our study has convincingly
      identified that 12 of 25 studied SNPs were strongly associated with one or more
      blood lipid parameters (TC, LDL, HDL and TG). Among the 12 associated SNPs, 10
      significantly influence the risk of one or more types of dyslipidemia.We firstly
      found four SNPs (rs12654264 in HMGCR; rs2479409 in PCSK9; rs16996148 in CILP2,
      PBX4; rs4420638 in APOE-C1-C4-C2) robustly and independently associate with four
      types of dyslipidemia (MHL, mixed hyperlipidemia; IHTC, isolated
      hypercholesterolemia; ILH, isolated low HDL-C; IHTG, isolated
      hypertriglyceridemia). Our results suggest that genetic susceptibility is
      different on the same candidate locus for the different populations. Meanwhile,
      most of the reported genetic variants strongly influence one or more plasma lipid
      levels and the risk of dyslipidemia in Chinese population.

PMID- 29321359
TI  - Association of lactase 13910 C/T polymorphism with bone mineral density and
      fracture risk: a meta-analysis.
AB  - A number of studies have investigated the association of lactase (LCT,C/T-13910)
      gene polymorphismwith bonemineral density (BMD) and fracture risk, but previous
      results were inconclusive. In this study, a meta-analysis was performed to
      quantify the association of LCT (C/T-13910) polymorphism with BMD and fracture
      risk. Eligible publications were searched in the PubMed, Web of Science, Embase
      databases, Google Scholar, Yahoo and Baidu. Pooled weighed mean difference (WMD)
      or odds ratio (OR) with their 95% confidence interval (CI) were calculated using
      a fixed-effects or random-effects model. A total of nine articles with 8871
      subjects were investigated in the presentmeta-analysis. Overall, the TT/TC
      genotypes of LCT 13910 C/T polymorphism showed significantly higher BMD than
      those with the CC genotype at femur neck (FN) (WMD = 0.011 g/cm2, 95% CI = 0.004
      0.018, P = 0.003). Besides, LCT 13910 C/T polymorphism may decrease the risk of
      any site fractures (for TT versus TC+CC, OR = 0.813, 95% CI = 0.704-0.938, P =
      0.005; for T allele versus C allele, OR = 0.885, 95% CI = 0.792-0.989, P =
      0.032). However, there was no significant association of LCT 13910 C/T
      polymorphism with BMD at lumbar spine and risk of vertebral fractures under all
      genetic contrast models (all P values were >0.05). The meta-analysis suggests
      that there are significant effects of LCT 13910 C/T polymorphism on BMD and
      fracture risk. Large-scale studies with different ethnic populations will be
      needed to further investigate the possible race-specific effect of LCT 13910 C/T
      polymorphism on BMD and fracture risk.

PMID- 29321360
TI  - Ellis-van Creveld syndrome and profound deafness resulted by sequence variants in
      the EVC/EVC2 and TMC1 genes.
AB  - Ellis-van Creveld syndrome is an autosomal recessive skeletal dysplasia primarily
      characterized by the features such as disproportionate dwarfism, short ribs,
      short limbs, dysplastic nails, cardiovascular malformations, post-axial
      polydactyly (PAP) (bilateral) of hands and feet. EVC/EVC2 located in head-to-head
      arrangement on chromosome 4p16 are the causative genes for EvC syndrome. In the
      study, we present two families, A and B, with Pakistani and Republic of Kosovo
      origin, respectively. They showed features of EvC syndrome and were clinically
      and genetically characterized. In family A, the affected members showed an
      additional feature of profound deafness. The whole exome sequencing (WES) in this
      family revealed two homozygous variants in EVC2 (c.30dupC; p.Thr11Hisfs*45) and
      TMC1 (c.1696-1G>A) genes. In family B, WES revealed novel compound heterozygous
      variants (p.Ser307Pro, c.2894+3A>G) in the EVC gene. This study reports first
      case of variants in the genes causing EvC syndrome and profound deafness in the
      same family.

PMID- 29321361
TI  - A novel contiguous deletion involving NDP, MAOB and EFHC2 gene in a patient with
      familial Norrie disease: bilateral blindness and leucocoria without other
      deficits.
AB  - Contiguous microdeletions of the Norrie disease pseudoglioma (NDP) region on
      chromosome Xp11.3 have been widely confirmed as contributing to the typical
      clinical features of Norrie disease (ND). However, the precise relation between
      genotype and phenotype could vary. The contiguous deletion of NDP and its
      neighbouring genes, MAOA/B and EFHC2, reportedly leads to syndromic clinical
      features such as microcephaly, intellectual disability, and epilepsy. Herewe
      report a novel contiguous microdeletion of the NDP region containing the MAOB and
      EFHC2 genes,which causes eye defects but no cognitive disability.We detected a
      deletion of 494.6 kb atXp11.3 in both the proband and carrier mother. This
      deletionwas then used as the molecular marker in prenatal diagnosis for two
      subsequent pregnancies. The deletion was absent in one of the foetuses, who
      remain without any abnormalities at 2 years of age. The proband shows the typical
      ocular clinical features of ND including bilateral retinal detachment,
      microphthalmia, atrophic irides, corneal opacification, and cataracts, but no
      symptoms of microcephaly, intellectual disability, and epilepsy. This familial
      study demonstrates that a deficiency in one of two MAO genes may not lead to
      psychomotor delay, and deletion of EFHC2 may not cause epilepsy. Our observations
      provide new information on the genotype-phenotype relations of MAOA/B and EFHC2
      genes involved in the contiguous deletions of ND.

PMID- 29321362
TI  - A novel missense mutation of ADAR1 gene in a Chinese family leading to
      dyschromatosis symmetrica hereditaria and literature review.
AB  - Dyschromatosis symmetrica hereditaria (DSH) is a rare autosomal dominant
      pigmentary genodermatosis, which is characterized by a mixture of hyperpigmented
      and hypopigmented macules on the dorsal of the hands and feet, and on the face
      presented like freckle. Identification of RNA-specific adenosine deaminase 1
      (ADAR1) gene results in DSH. This study was mainly to explore the pathogenic
      mutation of ADAR1 gene and provide genetics counselling and prenatal diagnostic
      testing for childbearing individuals.Mutational analysis of ADAR1 gene was
      performed by polymerase chain reaction (PCR) and electrophoretic separation of
      PCR products by 1.5% agarose gel electrophoresis. The coding exons and
      intron/exon flanking regions followed by bidirectional sequencing was performed
      on all participants. In this study, we found that a 28 year-old male patient
      harbouring a deleterious substitution of Leu1052Pro in the ADAR1 gene in a
      typical DSH family. His mother suffered from the DSH also owns the same mutation.
      This mutation, however, is not identified in the unaffected members in this
      family and those 200 normal controls. In summary, this new mutation Leu1052Pro
      reported here is pathogenic and detrimental for DSH. Our finding not only
      enriches mutation database and contributes to dissecting further the correlation
      between mutation position and phenotypical features of DSH, but also provides
      genetics counselling and prenatal diagnostic testing for childbearing couple.

PMID- 29321363
TI  - Dominance effects estimation of TLR4 and CACNA2D1 genes for health and production
      traits using logistic regression.
AB  - Knowledge of nonadditive variance and genetic effects can be helpful in
      explaining the total genetic variation formost of the traits. The objective of
      this study was to estimate dominance effects of several single-nucleotide
      polymorphism (SNP) genotypes for the production traits and clinical mastitis
      residual (CMR), in Holstein dairy cattle in a case-control study. Records of 305
      days lactation were obtained for production traits and CMR. Animals were selected
      based on extreme values for CMR from mixed model analyses. Samples were genotyped
      for four SNP-single genotypes and their associations with production traits
      (breeding values for protein and fat yield, and protein and fat percentage) were
      estimated by applying logistic regression analyses. Calculation of contrast
      between both homozygous and heterozygous genotypes permitted to estimate
      dominance effects, which ranged from -0.49 to 0.35 standard deviation units for
      the production traits and clinical mastitis (CM), respectively. Results showed
      that the dominance effects may be important in contribution of total genetic
      effects for production traits and CM. Therefore, evaluation of animals based on
      additive variance alone and disregarding nonadditive effects may lead to failure
      in selection programmes and exactly estimating the genetic variation. The method
      that we used would help breeders in accurately estimation of genotypic values in
      a new genomic selection scenario including dominance effects.

PMID- 29321364
TI  - Illumina-based de novo transcriptome sequencing and analysis of Chinese forest
      musk deer.
AB  - The Chinese forest musk deer (Moschus berezovskii Flerov) is an endangered
      artiodactyl mammal. The musk secreted by sexually mature males is highly valued
      for alleged pharmaceutical properties and perfume manufacturing. However, the
      genomic and transcriptomic resources of musk deer remain deficiently represented
      and poorly understood. Next-generation sequencing technique is an efficient
      method for generating an enormous amount of sequence data that can represent a
      large number of genes and their expression levels. In the present study, we used
      Illumina HiSeq technology to perform de novo assembly of heart and musk gland
      transcriptomes from the Chinese forest musk deer. A total of 239,383 transcripts
      and 176,450 unigenes were obtained, of which 37,329 unigenes were matched to
      known sequences in the NCBI nonredundant protein (Nr) database; 31,039 unigenes
      were assigned to 61 GO terms, and 11,782 to 332 KEGG pathways. Additionally, 592
      and 2282 differentially expressed genes were found to be specifically expressed
      in the heart and musk gland, respectively. The abundant transcriptomic data
      generated in the present report will provide a comprehensive sequence resource
      for Chinese forest musk deer as well as lay down a foundation which will help in
      accelerating genetic and functional genomics research in this species.

PMID- 29321365
TI  - Genome-based exome sequencing analysis identifies GYG1, DIS3L and DDRGK1 are
      associated with myocardial infarction in Koreans.
AB  - Myocardial infarction (MI) is a complex disease caused by combination of genetic
      and environmental factors. Although genome-wide association studies (GWAS)
      identified more than 46 risk loci which are associated with coronary artery
      disease and MI, most of the genetic variability inMI still remains undefined.
      Here, we screened the susceptibility loci for MI using exome sequencing and
      validated candidate variants in replication sets. We identified that three genes
      (GYG1, DIS3L and DDRGK1) were associated with MI at the discovery and replication
      stages. Further research will be required to determine the functional association
      of these genes with MI risk, and these associations have to be confirmed in other
      ethnic populations.

PMID- 29321366
TI  - Venous thromboembolism associated with protein S deficiency due to Arg451*
      mutation in PROS1 gene: a case report and a literature review.
AB  - Protein S (PS) is a vitaminK-dependent glycoproteinwhich plays an important role
      in the regulation of blood coagulation. PS deficiency has been found in 1.5-7% of
      thrombophilic patients. Here, we report the first Polish case with PS deficiency
      caused by the p.Arg451* in the PROS1 gene detected in a 21-year-old man with
      trauma-induced venous thromboembolism. To our knowledge, we provided the review
      of all the available data on this mutation (a total of 56 cases). The proband,
      his mother and his sister were screened for thrombophilia. To elucidate genetic
      background of PS deficiency, all PROS1 genes were subjected to direct sequencing.
      The free PS levels were 35% in the proband, 21% in the proband's mother and 28%
      in the proband's sister and their PS total levels were 37.1, 47.5 and 55.1%,
      respectively. Type I PS deficiency was diagnosed. In all patients, genetic
      analysis revealed the presence of heterozygous nonsense mutation (c.1351C>T;
      p.Arg451*) located in exon 12 of PROS1 gene. This mutation interrupts the reading
      frame by premature termination codon at position 451 and may lead to the
      production of truncated protein. The present case combined with the review of the
      literature suggests that p.Arg451* in the PROS1 gene mainly leads to clinically
      evident thrombosis following trauma, surgery or serious comorbidities especially
      malignancy.

PMID- 29321367
TI  - Drosophila pallidosa: whether a separate species or a light form of D. ananassae.
AB  - Drosophila pallidosa belongs to the D. ananassae complex, which includes a total
      of 10 species. Earlier D. pallidosa was known as light form of D. ananassae but
      later it was described as a new species, sibling of D. ananassae. Both these
      terms, light form and sibling species were used by Futch. This makes the
      taxonomic status of D. pallidosa confusing. In this review we have tried to
      understand the actual status of this sibling species pair. Considering the
      similarities and dissimilarities, we suggest that D. pallidosa does not have the
      full status of a species, rather it is in the process of speciation, statu
      nascendi. Our suggestion is strengthened by the fact that male genitalia are
      identical in both the cases and they lack postmating reproductive isolation since
      hybrids between them are normal and fully fertile.

PMID- 29321368
TI  - VKOR paralog VKORC1L1 supports vitamin K-dependent protein carboxylation in vivo.
AB  - Vertebrates possess 2 proteins with vitamin K oxidoreductase (VKOR) activity:
      VKORC1, whose vitamin K reduction supports vitamin K-dependent (VKD) protein
      carboxylation, and VKORC1-like 1 (VKORC1L1), whose function is unknown. VKD
      proteins include liver-derived coagulation factors, and hemorrhaging and
      lethality were previously observed in mice lacking either VKORC1 or the gamma
      glutamyl carboxylase (GGCX) that modifies VKD proteins. Vkorc1-/- mice survived
      longer (1 week) than Ggcx-/- mice (midembryogenesis or birth), and we assessed
      whether VKORC1L1 could account for this difference. We found that Vkorc1-/
      ;Vkorc1l1-/- mice died at birth with severe hemorrhaging, indicating that
      VKORC1L1 supports carboxylation during the pre- and perinatal periods. Additional
      studies showed that only VKORC1 sustains hemostasis beyond P7. VKORC1 expression
      and VKOR activity increased during late embryogenesis and following birth, while
      VKORC1L1 expression was unchanged. At P0, most (>99%) VKOR activity was due to
      VKORC1. Prothrombin mRNA, protein, and carboxylation also increased during this
      period, as did mRNA levels of coagulation factors encoding genes F7, F9, and F10.
      VKORC1L1 levels in Vkorc1-/- mouse liver may therefore be insufficient for
      supporting carboxylation beyond day 7. In support of this conclusion, VKORC1L1
      overexpression in liver rescued carboxylation and hemostasis in adult Vkorc1-/-
      mice. These findings establish that VKORC1L1 supports VKD protein carboxylation
      in vivo.

PMID- 29321370
TI  - Activation-induced cytidine deaminase deficiency accelerates autoimmune diabetes
      in NOD mice.
AB  - B cells play an important role in type 1 diabetes (T1D) development. However, the
      role of B cell activation-induced cytidine deaminase (AID) in diabetes
      development is not clear. We hypothesized that AID is important in the
      immunopathogenesis of T1D. To test this hypothesis, we generated AID-deficient
      (AID-/-) NOD mice. We found that AID-/-NOD mice developed accelerated T1D, with
      worse insulitis and high levels of anti-insulin autoantibody in the circulation.
      Interestingly, neither maternal IgG transferred through placenta, nor IgA
      transferred through milk affected the accelerated diabetes development. AID-/-NOD
      mice showed increased activation and proliferation of B and T cells. We found
      enhanced T-B cell interactions in AID-/-NOD mice, with increased T-bet and IFN
      gamma expression in CD4+ T cells in the presence of AID-/- B cells. Moreover,
      excessive lymphoid expansion was observed in AID-/-NOD mice. Importantly, antigen
      specific BDC2.5 CD4+ T cells caused more rapid onset of diabetes when
      cotransferred with AID-/- B cells than when cotransferred with AID+/+ B cells.
      Thus, our study provides insights into the role of AID in T1D. Our data also
      suggest that AID is a negative regulator of immune tolerance and ablation of AID
      can lead to exacerbated islet autoimmunity and accelerated T1D development.

PMID- 29321369
TI  - Enhancing CAR T cell persistence through ICOS and 4-1BB costimulation.
AB  - Successful tumor eradication by chimeric antigen receptor-expressing (CAR
      expressing) T lymphocytes depends on CAR T cell persistence and effector
      function. We hypothesized that CD4+ and CD8+ T cells may exhibit distinct
      persistence and effector phenotypes, depending on the identity of specific
      intracellular signaling domains (ICDs) used to generate the CAR. First, we
      demonstrate that the ICOS ICD dramatically enhanced the in vivo persistence of
      CAR-expressing CD4+ T cells that, in turn, increased the persistence of CD8+ T
      cells expressing either CD28- or 4-1BB-based CARs. These data indicate that
      persistence of CD8+ T cells was highly dependent on a helper effect provided by
      the ICD used to redirect CD4+ T cells. Second, we discovered that combining ICOS
      and 4-1BB ICDs in a third-generation CAR displayed superior antitumor effects and
      increased persistence in vivo. Interestingly, we found that the membrane-proximal
      ICD displayed a dominant effect over the distal domain in third-generation CARs.
      The optimal antitumor and persistence benefits observed in third-generation
      ICOSBBz CAR T cells required the ICOS ICD to be positioned proximal to the cell
      membrane and linked to the ICOS transmembrane domain. Thus, CARs with ICOS and 4
      1BB ICD demonstrate increased efficacy in solid tumor models over our current 4
      1BB-based CAR and are promising therapeutics for clinical testing.

PMID- 29321371
TI  - Assessing drug efficacy against Plasmodium falciparum liver stages in vivo.
AB  - Malaria eradication necessitates new tools to fight the evolving and complex
      Plasmodium pathogens. These tools include prophylactic drugs that eliminate
      Plasmodium liver stages and consequently prevent clinical disease, decrease
      transmission, and reduce the propensity for resistance development. Currently,
      the identification of these drugs relies on in vitro P. falciparum liver stage
      assays or in vivo causal prophylaxis assays using rodent malaria parasites; there
      is no method to directly test in vivo liver stage activity of candidate
      antimalarials against the human malaria-causing parasite P. falciparum. Here, we
      use a liver-chimeric humanized mouse (FRG huHep) to demonstrate in vivo P.
      falciparum liver stage development and describe the efficacy of clinically used
      and candidate antimalarials with prophylactic activity. We show that daily
      administration of atovaquone-proguanil (ATQ-PG; ATQ, 30 mg/kg, and PG, 10 mg/kg)
      protects 5 of 5 mice from liver stage infection, consistent with the use in
      humans as a causal prophylactic drug. Single-dose primaquine (60 mg/kg) has
      similar activity to that observed in humans, demonstrating the activity of this
      drug (and its active metabolites) in FRG huHep mice. We also show that DSM265, a
      selective Plasmodial dihydroorotate dehydrogenase inhibitor with causal
      prophylactic activity in humans, reduces liver stage burden in FRG huHep mice.
      Finally, we measured liver stage-to-blood stage transition of the parasite, the
      ultimate readout of prophylactic activity and measurement of infective capacity
      of parasites in the liver, to show that ATQ-PG reduces blood stage patency to
      below the limit of quantitation by quantitative PCR (qPCR). The FRG huHep model,
      thus, provides a platform for preclinical evaluation of drug candidates for liver
      stage causal prophylactic activity, pharmacokinetic/pharmacodynamics studies, and
      biological studies to investigate the mechanism of action of liver stage active
      antimalarials.

PMID- 29321372
TI  - Chronic skin inflammation accelerates macrophage cholesterol crystal formation
      and atherosclerosis.
AB  - Inflammation is critical to atherogenesis. Psoriasis is a chronic inflammatory
      skin disease that accelerates atherosclerosis in humans and provides a compelling
      model to understand potential pathways linking these diseases. A murine model
      capturing the vascular and metabolic diseases in psoriasis would accelerate our
      understanding and provide a platform to test emerging therapies. We aimed to
      characterize a new murine model of skin inflammation (Rac1V12) from a
      cardiovascular standpoint to identify novel atherosclerotic signaling pathways
      modulated in chronic skin inflammation. The RacV12 psoriasis mouse resembled the
      human disease state, including presence of systemic inflammation, dyslipidemia,
      and cardiometabolic dysfunction. Psoriasis macrophages had a proatherosclerotic
      phenotype with increased lipid uptake and foam cell formation, and also showed a
      6-fold increase in cholesterol crystal formation. We generated a triple-genetic
      K14-RacV12-/+/Srb1-/-/ApoER61H/H mouse and confirmed psoriasis accelerates
      atherogenesis (~7-fold increase). Finally, we noted a 60% reduction in superoxide
      dismutase 2 (SOD2) expression in human psoriasis macrophages. When SOD2 activity
      was restored in macrophages, their proatherogenic phenotype reversed. We
      demonstrate that the K14-RacV12 murine model captures the cardiometabolic
      dysfunction and accelerates vascular disease observed in chronic inflammation and
      that skin inflammation induces a proatherosclerotic macrophage phenotype with
      impaired SOD2 function, which associated with accelerated atherogenesis.

PMID- 29321373
TI  - The current state of biomarkers of mild traumatic brain injury.
AB  - Mild traumatic brain injury (mTBI) is a common occurrence, with over 3 million
      cases reported every year in the United States. While research into the
      underlying pathophysiology is ongoing, there is an urgent need for better
      clinical guidelines that allow more consistent diagnosis of mTBI and ensure safe
      return-to-play timelines for athletes, nonathletes, and military personnel. The
      development of a suite of biomarkers that indicate the pathogenicity of mTBI
      could lead to clinically useful tools for establishing both diagnosis and
      prognosis. Here, we review the current evidence for mTBI biomarkers derived from
      investigations of the multifactorial pathology of mTBI. While the current
      literature lacks the scope and size for clarification of these biomarkers'
      clinical utility, early studies have identified some promising candidates.

PMID- 29321374
TI  - Selective CD28 blockade attenuates CTLA-4-dependent CD8+ memory T cell effector
      function and prolongs graft survival.
AB  - Memory T cells pose a significant problem to successful therapeutic control of
      unwanted immune responses during autoimmunity and transplantation, as they are
      differentially controlled by cosignaling receptors such as CD28 and CTLA-4.
      Treatment with abatacept and belatacept impede CD28 signaling by binding to CD80
      and CD86, but they also have the unintended consequence of blocking the ligands
      for CTLA-4, a process that may inadvertently boost effector responses. Here, we
      show that a potentially novel anti-CD28 domain antibody (dAb) that selectively
      blocks CD28 but preserves CTLA-4 coinhibition confers improved allograft survival
      in sensitized recipients as compared with CTLA-4 Ig. However, both CTLA-4 Ig and
      anti-CD28 dAb similarly and significantly reduced the accumulation of donor
      reactive CD8+ memory T cells, demonstrating that regulation of the expansion of
      CD8+ memory T cell populations is controlled in part by CD28 signals and is not
      significantly impacted by CTLA-4. In contrast, selective CD28 blockade was
      superior to CTLA-4 Ig in inhibiting IFN-gamma, TNF, and IL-2 production by CD8+
      memory T cells, which in turn resulted in reduced recruitment of innate CD11b+
      monocytes into allografts. Importantly, this superiority was CTLA-4 dependent,
      demonstrating that effector function of CD8+ memory T cells is regulated by the
      balance of CD28 and CTLA-4 signaling.

PMID- 29321375
TI  - Highly potent visnagin derivatives inhibit Cyp1 and prevent doxorubicin
      cardiotoxicity.
AB  - Anthracyclines such as doxorubicin are highly effective chemotherapy agents used
      to treat many common malignancies. However, their use is limited by
      cardiotoxicity. We previously identified visnagin as protecting against
      doxorubicin toxicity in cardiac but not tumor cells. In this study, we sought to
      develop more potent visnagin analogs in order to use these analogs as tools to
      clarify the mechanisms of visnagin-mediated cardioprotection. Structure-activity
      relationship studies were performed in a zebrafish model of doxorubicin
      cardiomyopathy. Movement of the 5-carbonyl to the 7 position and addition of
      short ester side chains led to development of visnagin analogs with 1,000-fold
      increased potency in zebrafish and 250-fold increased potency in mice. Using
      proteomics, we discovered that doxorubicin caused robust induction of Cytochrome
      P450 family 1 (CYP1) that was mitigated by visnagin and its potent analog 23.
      Treatment with structurally divergent CYP1 inhibitors, as well as knockdown of
      CYP1A, prevented doxorubicin cardiomyopathy in zebrafish. The identification of
      potent cardioprotective agents may facilitate the development of new therapeutic
      strategies for patients receiving cardiotoxic chemotherapy. Moreover, these
      studies support the idea that CYP1 is an important contributor to doxorubicin
      cardiotoxicity and suggest that modulation of this pathway could be beneficial in
      the clinical setting.

PMID- 29321376
TI  - Retinal de novo lipogenesis coordinates neurotrophic signaling to maintain
      vision.
AB  - Membrane lipid composition is central to the highly specialized functions of
      neurological tissues. In the retina, abnormal lipid metabolism causes severe
      forms of blindness, often through poorly understood neuronal cell death. Here, we
      demonstrate that deleting the de novo lipogenic enzyme fatty acid synthase (FAS)
      from the neural retina, but not the vascular retina, results in progressive
      neurodegeneration and blindness with a temporal pattern resembling rodent models
      of retinitis pigmentosa. Blindness was not rescued by protection from light
      evoked activity; by eating a diet enriched in palmitate, the product of the FAS
      reaction; or by treatment with the PPARalpha agonist fenofibrate. Vision loss was
      due to aberrant synaptic structure, blunted responsiveness to glial-derived
      neurotrophic factor and ciliary neurotrophic factor, and eventual apoptotic cell
      loss. This progressive neurodegeneration was associated with decreased membrane
      cholesterol content, as well as loss of discrete n-3 polyunsaturated fatty acid-
      and saturated fatty acid-containing phospholipid species within specialized
      membrane microdomains. Neurotrophic signaling was restored by exogenous
      cholesterol delivery. These findings implicate de novo lipogenesis in
      neurotrophin-dependent cell survival by maintaining retinal membrane
      configuration and lipid composition, and they suggest that ongoing lipogenesis
      may be required to prevent cell death in many forms of retinopathy.

PMID- 29321378
TI  - Glutamine-derived 2-hydroxyglutarate is associated with disease progression in
      plasma cell malignancies.
AB  - The production of the oncometabolite 2-hydroxyglutarate (2-HG) has been
      associated with c-MYC overexpression. c-MYC also regulates glutamine metabolism
      and drives progression of asymptomatic precursor plasma cell (PC) malignancies to
      symptomatic multiple myeloma (MM). However, the presence of 2-HG and its clinical
      significance in PC malignancies is unknown. By performing 13C stable isotope
      resolved metabolomics (SIRM) using U[13C6]Glucose and U[13C5]Glutamine in human
      myeloma cell lines (HMCLs), we show that 2-HG is produced in clonal PCs and is
      derived predominantly from glutamine anaplerosis into the TCA cycle. Furthermore,
      the 13C SIRM studies in HMCLs also demonstrate that glutamine is preferentially
      utilized by the TCA cycle compared with glucose. Finally, measuring the levels of
      2-HG in the BM supernatant and peripheral blood plasma from patients with
      precursor PC malignancies such as smoldering MM (SMM) demonstrates that
      relatively elevated levels of 2-HG are associated with higher levels of c-MYC
      expression in the BM clonal PCs and with a subsequent shorter time to progression
      (TTP) to MM. Thus, measuring 2-HG levels in BM supernatant or peripheral blood
      plasma of SMM patients offers potential early identification of those patients at
      high risk of progression to MM, who could benefit from early therapeutic
      intervention.

PMID- 29321377
TI  - Development of an airway mucus defect in the cystic fibrosis rat.
AB  - The mechanisms underlying the development and natural progression of the airway
      mucus defect in cystic fibrosis (CF) remain largely unclear. New animal models of
      CF, coupled with imaging using micro-optical coherence tomography, can lead to
      insights regarding these questions. The Cftr-/- (KO) rat allows for longitudinal
      examination of the development and progression of airway mucus abnormalities. The
      KO rat exhibits decreased periciliary depth, hyperacidic pH, and increased mucus
      solid content percentage; however, the transport rates and viscoelastic
      properties of the mucus are unaffected until the KO rat ages. Airway submucosal
      gland hypertrophy develops in the KO rat by 6 months of age. Only then does it
      induce increased mucus viscosity, collapse of the periciliary layer, and delayed
      mucociliary transport; stimulation of gland secretion potentiates this evolution.
      These findings could be reversed by bicarbonate repletion but not pH correction
      without counterion donation. These studies demonstrate that abnormal surface
      epithelium in CF does not cause delayed mucus transport in the absence of
      functional gland secretions. Furthermore, abnormal bicarbonate transport
      represents a specific target for restoring mucus clearance, independent of
      effects on periciliary collapse. Thus, mature airway secretions are required to
      manifest the CF defect primed by airway dehydration and bicarbonate deficiency.

PMID- 29321379
TI  - A glucose-responsive insulin therapy protects animals against hypoglycemia.
AB  - Hypoglycemia is commonly associated with insulin therapy, limiting both its
      safety and efficacy. The concept of modifying insulin to render its glucose
      responsive release from an injection depot (of an insulin complexed exogenously
      with a recombinant lectin) was proposed approximately 4 decades ago but has been
      challenging to achieve. Data presented here demonstrate that mannosylated insulin
      analogs can undergo an additional route of clearance as result of their
      interaction with endogenous mannose receptor (MR), and this can occur in a
      glucose-dependent fashion, with increased binding to MR at low glucose. Yet,
      these analogs retain capacity for binding to the insulin receptor (IR). When the
      blood glucose level is elevated, as in individuals with diabetes mellitus, MR
      binding diminishes due to glucose competition, leading to reduced MR-mediated
      clearance and increased partitioning for IR binding and consequent glucose
      lowering. These studies demonstrate that a glucose-dependent locus of insulin
      clearance and, hence, insulin action can be achieved by targeting MR and IR
      concurrently.

PMID- 29321382
TI  - [Chinese Journal of Nuclear Medicine and Molecular Imaging Volume 37, Number 12,
      December 25, 2017].

PMID- 29321381
TI  - Association between genetic polymorphism and levothyroxine bioavailability in
      hypothyroid patients.
AB  - Thyroid hormones play a vital role in the human body for growth and
      differentiation, regulation of energy metabolism, and physiological function.
      Hypothyroidism is a common endocrine disorder, which generally results from
      diminished normal circulating concentrations of serum thyroxine (fT4) and
      triiodothyronine (fT3). The primary choice in hypothyroidism treatment is oral
      administration of levothyroxine (L-T4), a synthetic T4 hormone, as approximately
      100-125 MUg/day. Generally, dose adjustment is made by trial and error approach.
      However, there are several factors which might influence bioavailability of L-T4
      treatment. Genetic background could be an important factor in hypothyroid
      patients as well as age, gender, concurrent medications and patient compliance.
      The concentration of thyroid hormones in tissue is regulated by both deiodinases
      enzyme and thyroid hormone transporters. In the present study, it was aimed to
      evaluate the effects of genetic differences in the proteins and enzymes (DIO1,
      DIO2, TSHR, THR and UGT) which are efficient in thyroid hormone metabolism and
      bioavailability of L-T4 in Turkish population. According to our findings,
      rs225014 and rs225015 variants in DIO2, which catalyses the conversion of
      thyroxine (pro-hormone) to the active thyroid hormone, were associated with TSH
      levels. It should be given lower dose to the patients with rs225014 TT and
      rs225015 GG genotypes in order to provide proper treatment with higher
      effectivity and lower toxicity.

PMID- 29321380
TI  - Renin-angiotensin-aldosterone system activation in long-standing type 1 diabetes.
AB  - BACKGROUND: In type 1 diabetes (T1D), adjuvant treatment with inhibitors of the
      renin-angiotensin-aldosterone system (RAAS), which dilate the efferent arteriole,
      is associated with prevention of progressive albuminuria and renal dysfunction.
      Uncertainty still exists as to why some individuals with long-standing T1D
      develop diabetic kidney disease (DKD) while others do not (DKD resistors). We
      hypothesized that those with DKD would be distinguished from DKD resistors by the
      presence of RAAS activation. METHODS: Renal and systemic hemodynamic function was
      measured before and after exogenous RAAS stimulation by intravenous infusion of
      angiotensin II (ANGII) in 75 patients with prolonged T1D durations and in equal
      numbers of nondiabetic controls. The primary outcome was change in renal vascular
      resistance (RVR) in response to RAAS stimulation, a measure of endogenous RAAS
      activation. RESULTS: Those with DKD had less change in RVR following exogenous
      RAAS stimulation compared with DKD resistors or controls (19%, 29%, 31%, P =
      0.008, DKD vs. DKD resistors), reflecting exaggerated endogenous renal RAAS
      activation. All T1D participants had similar changes in renal efferent arteroilar
      resistance (9% vs. 13%, P = 0.37) irrespective of DKD status, which reflected
      less change versus controls (20%, P = 0.03). In contrast, those with DKD
      exhibited comparatively less change in afferent arteriolar vascular resistance
      compared with DKD resistors or controls (33%, 48%, 48%, P = 0.031, DKD vs. DKD
      resistors), indicating higher endogenous RAAS activity. CONCLUSION: In long
      standing T1D, the intrarenal RAAS is exaggerated in DKD, which unexpectedly
      predominates at the afferent rather than the efferent arteriole, stimulating
      vasoconstriction. FUNDING: JDRF operating grant 17-2013-312.

PMID- 29321383
TI  - Higher Incidence of Sleep Disturbance among Survivors with Musculoskeletal Pain
      after the Great East Japan Earthquake: A Prospective Study.
AB  - Sleep disturbance is a common symptom after natural disasters. Although
      musculoskeletal pain also increases after natural disasters, its relation to
      sleep disturbance is not clear. The purpose of this study was to determine the
      influence of musculoskeletal pain on new-onset sleep disturbance among survivors
      after the Great East Japan Earthquake (GEJE). A prospective cohort study was
      conducted with the survivors of the GEJE at two and three years after the
      earthquake. New-onset sleep disturbance was defined as sleep disturbance absent
      at two years and present at three years after the earthquake. The sites of
      musculoskeletal pain included low back, shoulder, knee, and hand or foot. The
      number of musculoskeletal pain sites at two years after the earthquake was
      divided into three categories (0, 1, and 2 or more). Univariate and multivariate
      logistic regression models were used to calculate the odds ratio (OR) and 95%
      confidence interval (95%CI) for new-onset sleep disturbance according to the
      number of musculoskeletal pain sites. A total of 1,102 survivors were included in
      this study and 14.6% of the participants reported new-onset sleep disturbance.
      Using "0" as a reference, the adjusted ORs (95% CI) for new-onset sleep
      disturbance were 2.43 (1.55-3.80) in "1" and 2.96 (1.88-4.64) in "2 or more",
      respectively (P for trends < 0.001). In conclusion, this is the first study
      showing higher incidence of sleep disturbance among survivors with
      musculoskeletal pain after the GEJE. Care for musculoskeletal pain is important
      to prevent sleep disturbance after natural disasters.

PMID- 29321385
TI  - Severe Compression of the Left Main Coronary Artery in a Patient with Chronic
      Thromboembolic Pulmonary Hypertension.
AB  - Extrinsic compression of the left main coronary artery (LMCA) can occur in
      patients with an enlarged pulmonary artery trunk secondary to severe pulmonary
      hypertension (PH). This phenomenon rarely occurs in PH; moreover, few reports
      have shown that chronic thromboembolic PH can be a triggering factor for this
      syndrome. Herein, we describe a patient with extrinsic compression of the LMCA
      with chronic thromboembolic PH who underwent pulmonary endarterectomy and
      coronary artery bypass grafting successfully. Intravenous ultrasonography (IVUS)
      was effective for detecting and assessing the compression.

PMID- 29321384
TI  - Discovery of a Novel Fluoroquinolone Antibiotic Candidate WFQ-228 with Potent
      Antimicrobial Activity and the Potential to Overcome Major Drug Resistance.
AB  - WFQ-101 with a unique N-1 substituent, 5-amino-4-fluoro-2-(hydroxymethyl)phenyl
      group, was selected as a lead compound through combination screening based on
      antimicrobial activity and the efflux index against quinolone-resistant (QR)
      Pseudomonas aeruginosa (P. aeruginosa). Through structural optimization, we
      identified WFQ-228 as a novel fluoroquinolone antibiotic candidate. WFQ-228 had
      potent and superior activity in comparison to levofloxacin (LVX) and
      ciprofloxacin (CIP) against clinical isolates of P. aeruginosa, Escherichia coli
      and Acinetobacter baumannii, including QR strains. Furthermore, WFQ-228
      demonstrated the potential to overcome major mechanisms of drug resistance; its
      antimicrobial activity was less affected by both pump-mediated efflux and
      mutations of the quinolone resistance-determining region in P. aeruginosa
      compared with LVX and CIP. These results suggest that WFQ-228 is a promising
      candidate for further evaluation in the treatment of infections caused by QR Gram
      negative pathogens.

PMID- 29321386
TI  - [The 68th Regional Meeting (Kita Area)].

PMID- 29321387
TI  - [The 137th Regional Meeting (Kanto Area)].

PMID- 29321388
TI  - Suppression of Abdominal Aortic Aneurysm Formation in Mice by Teneligliptin, a
      Dipeptidyl Peptidase-4 Inhibitor.
AB  - AIM: Dipeptidyl peptidase-4 (DPP-4) inhibitors lower blood glucose levels through
      inhibition of incretin degradation, which stimulates insulin secretion. Recent
      studies reported that DPP-4 inhibitors suppressed atherogenesis in apolipoprotein
      E-knockout (ApoEKO) mice. In this study, we investigated whether teneligliptin, a
      DPP-4 inhibitor, affects the development of abdominal aortic aneurysms (AAA) in
      ApoEKO mice. METHODS: ApoEKO mice were fed a high-fat diet (HFD) and infused with
      angiotensin (Ang) II by osmotic mini pumps for 4 weeks to induce AAA with (DPP-4i
      group) or without (control group) teneligliptin administered orally from 1 week
      before HFD and Ang II infusion to the end of the experiment. Confluent rat
      vascular smooth muscle cells (VSMCs) were serum-starved for 48 hours, then
      incubated with or without teneligliptin for another 24 hours and stimulated with
      Ang II. RESULTS: Treatment with teneligliptin significantly reduced the AAA
      formation rate (30.7% vs. 71.4% vs. control, P<0.05), aortic dilatation (1.32+/
      0.09 mm vs. 1.76+/-0.18 mm in the control, P<0.05) and severity score (0.75+/
      0.28 vs. 1.91+/-0.4 in the control, P<0.05). Elastin degradation grade was also
      attenuated in DPP-4i group (2.83+/-0.17 vs. 3.45+/-0.16 in the control, P<0.05).
      The number of macrophages infiltrating into the abdominal aorta was decreased in
      the DPP-4i group (51.8+/- 29.8/section vs. 219.5+/-78.5/section in the control,
      P<0.05). Teneligliptin attenuated Ang II-induced phosphorylation of extracellular
      signal-regulated kinase (ERK) and Akt, and mRNA expression of monocyte
      chemoattractant protein-1 in VSMCs. CONCLUSION: Treatment with teneligliptin
      suppressed AAA formation in ApoEKO mice with HFD and Ang II infusion. Suppression
      of macrophage infiltration by teneligliptin may be involved in the inhibition of
      AAA formation.

PMID- 29321389
TI  - Aortic Root Calcification Score as an Independent Factor for Predicting Major
      Adverse Cardiac Events in Familial Hypercholesterolemia.
AB  - AIM: The aims of this study were: 1) to determine whether the accumulation of
      aortic root calcification (ARC) assessed using coronary computed tomography
      angiography (CCTA) can predict future cardiovascular events, and 2) to estimate
      the onset and progression of ARC in patients with familial hypercholesterolemia
      (FH). METHODS: One hundred thirteen consecutive Japanese patients with
      heterozygous FH (male=54, mean age=52.1+/-15.6 years, mean LDL-C=299.0+/-94.6
      mg/dL), without known coronary artery disease, who underwent 64-detector row CCTA
      were retrospectively evaluated. ARC was defined as the presence of calcium at the
      aortic root. The extent of ARC was expressed in Agatston units as the ARC-score.
      Major adverse cardiac events (MACE) were defined as either cardiac death, ST
      elevated myocardial infarction (STEMI), non-ST elevated myocardial infarction
      (NSTEMI), unstable angina pectoris (UAP), planned percutaneous coronary
      intervention (PCI), coronary artery bypass grafting (CABG), or stroke. The
      periods to MACE were estimated using multivariate logistic regression analysis.
      RESULTS: During the follow-up period (median 1635 days), 19 instances of MACE
      occurred. Multivariate logistic regression analysis revealed that ARC was a
      significant independent predictor of MACE (OR=1.48; 95% CI 1.11-1.87, p<0.001,
      respectively). The regression equations were Y=0.09X- 1.59 (R2=0.34, p<0.001) in
      males and Y=0.08X-1.60 (R2=0.13, p<0. 05) in females. CONCLUSIONS: ARC was
      significantly associated with future MACE in Japanese patients with heterozygous
      FH. ARC may start to develop, on average, at 17.4 and 19.7 years of age in males
      and females, respectively, with heterozygous FH.

PMID- 29321390
TI  - Unsolved Antiatherogenic Mechanism of n-3 Polyunsaturated Fatty Acids.

PMID- 29321391
TI  - [Prothymosinalpha, as a neuroprotective DAMPs/Alarmins molecule].
AB  - Prothymosin alpha (ProTalpha) has been identified as an anti-necrotic factor from
      the conditioned medium of primary cultured of rat cortical neurons under the
      serum-free starving condition. ProTalpha is released in a non-vesicular manner
      from neurons or astrocytes by the help of cargo protein S100A13. Thus released
      ProTalpha is found to have robustness roles in the brain under the condition of
      neuronal necrosis or apoptosis. ProTalpha inhibits necrosis by plasma membrane
      translocation of glucose transporters endocytosed by ischemia/starving stress,
      through an activation of unidentified G protein-coupled receptor and protein
      kinase Cbeta. In the cerebral or retinal ischemia model, systemic injection of
      ProTalpha protects brain or retina from ischemic damages by converting necrosis
      to apoptosis, which is in turn blocked by neurotrophic factors. In the retinal
      ischemia model, ProTalpha prevents the damages by another mechanism through toll
      like receptor 4 (TLR4) and downstream TRIF signaling. The direct interaction
      between ProTalpha and TLR4/MD2 is also evidenced by the study of molecular
      dynamics and protein-protein interaction. All these findings indicate that
      ProTalpha could be called a cytoprotective member of damage-associated molecular
      patterns (DAMPs) or alarmins. ProTalpha and its modified peptide fragment, NEVDQE
      (P6Q) show the vasculoprotective actions by itself in a model of cerebral
      ischemia as well as neuroprotective actions. The concomitant administration of
      these peptides abolishes the cerebral hemorrhage induced tissue plasminogen
      activator (tPA), which is treated late after cerebral ischemia models. Thus,
      ProTalpha and P6Q seem to have promising therapeutic potencies to directly
      protect neurons and inhibit the hemorrhage by late treatment with tPA against
      stroke.

PMID- 29321393
TI  - [n-3 fatty acids and the maintenance of neuronal functions].
AB  - The functions of n-3 fatty acids are known to be diverse, and they play roles in
      cardiovascular and neuronal systems and in lipid metabolism. Docosahexaenoic acid
      (DHA), which is the most abundant n-3 fatty acid in the brain, is essential for
      the maintenance of brain functions throughout the human lifespan. Epidemiological
      studies have demonstrated that reduced n-3 fatty acid intake is closely
      associated with the onset of mental and neurological diseases such as brain
      developmental disorders, depression, and Alzheimer's disease. DHA is primarily
      involved in neurogenesis, synapse formation, neuronal differentiation, neurite
      outgrowth, maintenance of membrane fluidity, anti-inflammatory action, and
      antioxidant action. Its mechanism of action include: 1) the effects on ion
      channels and membrane bound receptors/enzymes achieved by changing membrane
      fluidity, as a cell membrane constituent, and 2) free DHA molecules, derived from
      the cell membrane that directly or metabolically, by conversion to protectin D1
      and other molecules, indirectly regulates the gene expression and the activity of
      intracellular proteins. Although future studies are required, the supplementation
      of n-3 fatty acids such as DHA may suppress the deterioration of brain functions,
      delay the onset and progression of various mental/neurological diseases, and
      further improve the outcome of the neuronal diseases.

PMID- 29321392
TI  - [The role of brain n-3 fatty acids-GPR40/FFAR1 signaling in pain].
AB  - G-protein-coupled receptor 40 (GPR40)/free fatty acid receptor (FFAR) 1 is
      activated by long-chain fatty acids such as docosahexaenoic acid (DHA). Its
      receptor is expressed predominantly in the central nervous system (CNS) and in
      beta-cells in the pancreatic Islets. We have already demonstrated that the
      intracerebroventricular administration of DHA or GW9508, a GPR40/FFAR1 agonist,
      suppresses formalin-induced pain behavior. It also attenuates complete Freund's
      adjuvant-induced mechanical allodynia and thermal hyperalgesia, suggesting that
      these effects occur by increasing beta-endorphin release from propiomelanocortin
      neurons. Furthermore, we found that the brain GPR40/FFAR1 signaling may involve
      in the regulation of the descending pain control system, whereas the deletion of
      GPR40/FFAR1 might exacerbate mechanical allodynia in postoperative pain.
      Therefore, it is possible that the brain n-3 fatty acid-GPR40/FFAR1 signaling may
      play a key role in the modulation of the endogenous pain control system and
      emotional function. Here, we discuss the role of brain n-3 fatty acids
      GPR40/FFAR1 signaling in a pain, and we review the current status and future
      prospects of the brain GPR40/FFAR1.

PMID- 29321394
TI  - [Chrono-nutrition and n-3 polyunsaturated fatty acid].
AB  - Circadian clock system has been widely maintained in many spices from prokaryote
      to mammals. "Circadian" means "approximately day" in Latin, thus circadian rhythm
      means about 24 hour rhythms. The earth revolves once every 24 hours, and our
      circadian system has been developed for adjusting to this 24 hour cycles, to get
      sun light information for getting their foods or for alive in birds or mammals.
      We have two different circadian systems so-called main oscillator located in the
      suprachiasmatic nucleus (SCN) of the hypothalamus, and local oscillator located
      in the various peripheral organ tissues such as liver, kidney and skeletal
      muscle. The SCN is directly entrained by light-dark information through retinal
      hypothalamic tract, and then organizes local clock in peripheral tissues via many
      pathways including neural and hormonal functions. On the other hand, peripheral
      local clocks are entrained by feeding, exercise and stress stimuli through
      several cell signaling. Foods (protein, carbohydrate, and lipid) are important
      regulator of circadian clocks in peripheral tissues. Thus, controlling the timing
      of food consumption and food composition, a concept known as chrononutrition, is
      one area of active research to aid recovery from many physiological dysfunctions.
      In this review, we focus on molecular mechanisms of entrainment and the
      relationships between circadian clock systems and n-3 polyunsaturated fatty acid.
      We concentrate on experimental data obtained from cells or animals and humans and
      discuss how these findings translate into clinical research, and we highlight the
      latest developments in chrononutritional studies.

PMID- 29321395
TI  - [HMGB1 as a representative DAMP and anti-HMGB1 antibody therapy].
AB  - High mobility group box-1 (HMGB1), a representative damage-associated molecular
      patterns (DAMPs), has been reported to be involved in many inflammatory diseases.
      To validate HMGB1 as a target molecule of inflammatory diseases and to examine
      the effects of inhibition of HMGB1 on the diseases, we raised anti-HMGB1
      monoclonal antibody (mAb) neutralizing extracellular HMGB1 and characterized it.
      We report the effects of anti-HMGB1 mAb on brain infarction, brain hemorrhage,
      brain trauma, epilepsy and neuropathic pain using animal models. In these wide
      range of disease conditions, we found a common event; the injury-induced
      translocation of HMGB1 from nuclei to extracellular space, especially in neurons.
      Released HMGB1 disrupt the integrity of blood-brain barrier (BBB) and increased
      the permeability of BBB, associated with inflammatory responses including the
      induction of pro-inflammatory cytokines. The intravenous injection of anti-HMGB1
      mAb inhibited translocation of HMGB1, BBB disruption, expression of inflammatory
      molecules and improved neurological symptoms of different kinds of disease
      models. These results as a whole indicated that HMGB1 may be a very sensitive
      factor which is mobilized readily by different injurious insults to the brain and
      that HMGB1 release may be present most upstream of cascade of events triggering
      BBB disruption and brain inflammation. Thus, HMGB1 may be an excellent target for
      the treatment of above-mentioned diseases. Anti-HMGB1 mAb provide a novel and
      potential therapy for these severe disease conditions.

PMID- 29321396
TI  - [Molecular and cellular mechanisms underlying the sterile inflammation after
      ischemic stroke].
AB  - Inflammation is an essential step for the pathology of ischemic stroke, and is
      also an important therapeutic target for developing novel therapeutic methods
      which have a wide therapeutic time window. Since there is no pathogen in the
      brain, the inflammation will be triggered by some endogenous molecules which are
      called as danger associated molecular patterns (DAMPs). So far two important
      DAMPs, high mobility group box 1 (HMGB1) and peroxiredoxin (PRX), have been
      recently identified in the ischemic brain. HMGB1 exaggerates the disruption of
      blood brain barrier; on the other hand, PRX activates mononuclear phagocytes and
      induces the inflammatory cytokine production through the activation of Toll-like
      receptor 2 (TLR2) and TLR4. Various inflammatory molecules produced from
      infiltrating immune cells have been known to exacerbate the neurological deficits
      of ischemic stroke patients. Recently, it has been paid attention that the
      inflammation after tissue injury also induces tissue repair, while its mechanisms
      remain to be clarified. Novel therapeutic methods will be established by
      clarifying detailed molecular mechanisms underlying the induction of neural
      repair after cerebral post-ischemic inflammation.

PMID- 29321398
TI  - Where Are the Secrets of Increased Thrombosis and Aneurysm Formation With the
      Current Bioresorbable Vascular Scaffolds Hidden?

PMID- 29321397
TI  - Associations between Socioeconomic Status and the Prevalence and Treatment of
      Hypercholesterolemia in a General Japanese Population: NIPPON DATA2010.
AB  - AIM: To investigate associations between socioeconomic status (SES) and the
      prevalence and treatment status of hypercholesterolemia in a general Japanese
      population. METHODS: In 2010, we established a cohort study of 2417 adults (age
      20-91 yr) from 300 randomly selected areas across Japan who participated in the
      National Health and Nutrition Survey of Japan. We cross-sectionally examined an
      association between SES and (1) prevalence of hypercholesterolemia in 2417
      participants (999 men and 1418 women) and (2) not receiving medication for
      hypercholesterolemia in 654 participants (215 men and 439 women). SES included
      employment status, marital status, length of education, and household
      expenditures. Hypercholesterolemia was defined as a total serum cholesterol level
      of >=6.21 mmol/L (240 mg/dL) or the use of lipid-lowering medications. RESULTS:
      The overall prevalence of hypercholesterolemia was 21.5% in men and 31.0% in
      women. In men, the lowest quintile of household expenditures was associated with
      a higher prevalence of hypercholesterolemia (28.3%) compared with the upper 4
      quintiles (19.9%) (multivariable-adjusted odds ratio 1.66; 95% confidence
      interval [CI] 1.16-2.38). Among participants with hypercholesterolemia, 55.4% of
      men and 55.1% of women were not receiving medication. Unmarried men were more
      likely to be untreated (75.0%) than married men (50.9%) (multivariable-adjusted
      odds ratio 2.53;95%CI 1.05-6.08). SES had no significant effects in women.
      CONCLUSION: In a general population of Japanese men, low household expenditures
      were associated with a higher prevalence of hypercholesterolemia, and unmarried
      men with hypercholesterolemia were less likely to receive medication.

PMID- 29321399
TI  - Where Are the Secrets of Increased Thrombosis and Aneurysm Formation With the
      Current Bioresorbable Vascular Scaffolds Hidden? - Reply.

PMID- 29321400
TI  - Report of the American Heart Association (AHA) Scientific Session 2017, Anaheim,
      California.
AB  - On November 11-15, the American Heart Association (AHA) Scientific Sessions 2017
      were held in Anaheim, California, for the first time in 16 years. The annual
      sessions attracted nearly 18,000 attendees, with a global presence from more than
      100 countries, and featured 5 days of programming for cardiovascular basic
      scientists, clinicians, and researchers. As usual, activities of participants
      from Japan were prominent. From the exciting sessions, I report the topics and
      key presentations including the late-breaking clinical trials.

PMID- 29321401
TI  - Has the Development of Drug-Eluting Stents Ended With Limus-Eluting Stents?

PMID- 29321402
TI  - Cerebrotendinous Xanthomatosis with Nodular-hypertrophy of the Lumbosacral Roots.

PMID- 29321403
TI  - A Patient with a Massive Single Cardiac Metastasis of Lung Adenocarcinoma,
      Diagnosed via a Biopsy.
AB  - A patient with a history of lung adenocarcinoma was admitted because of
      palpitation. Transthoracic echocardiogram revealed a mass (74*42 mm) in the right
      ventricle. Computed tomography showed a tumor lesion in the right ventricular
      cavity but no other distant metastasis. Coronary angiography revealed well
      developed small branches to the tumor. After right heart catheterization, a
      pathological analysis of a tumor biopsy demonstrated adenocarcinoma. We diagnosed
      the patient with right ventricular metastasis of lung cancer. With large cardiac
      metastasis, a tumor biopsy with a right heart catheter may help obtain a
      pathological diagnosis and also serve as a re-biopsy to confirm the gene mutation
      status.

PMID- 29321404
TI  - A Clinicopathological Analysis of Six Autopsy Cases of Sudden Unexpected Death
      due to Infectious Aortitis in Patients with Aortic Tears.
AB  - Objective Cardiovascular disease is a leading cause of sudden unexpected death
      even in hospitalized patients. Infectious aortitis is a rare disease that has the
      potential to cause aortic tears and hemorrhage followed by sudden death. The aim
      of this study was to reveal the clinicopathological features of infectious
      aortitis that are related to sudden unexpected death. Methods We retrospectively
      reviewed 1,310 autopsy cases over 15 years and selected the cases involving
      patients who died suddenly due to aortic tears. We analyzed the clinical
      information and pathological findings. Results One hundred thirty-three of 1,310
      cases (10.2%) were autopsied under the clinical diagnosis of unexpected sudden
      death. Aortic tears were identified in 33 cases (2.5%) and infectious aortitis
      was diagnosed in 6 (18.2%) of these cases. All cases involved male patients
      (middle-aged to elderly) with risk factors for atherosclerosis (i.e.,
      hypertension). The laboratory data showed continuous leukocytosis and C-reactive
      protein elevation, even during the improvement phase, in patients with pre
      existing infectious disease. The autopsy findings revealed three types of aortic
      tears (aneurysms, dissections and penetrating atherosclerotic ulcers with
      moderate to severe atherosclerosis), and the infiltration of numerous neutrophils
      at the site of rupture. Gram-positive bacteria were detected in four cases and
      Gram-negative bacteria were detected in two cases. Discussion We demonstrated
      that sudden unexpected death caused by infectious aortitis rarely occurred in
      hospitalized patients, even in the recovery phase of the preceding infectious
      disease. We therefore recommend that clinicians pay attention to infectious
      aortitis in patients with infectious disease, particularly elderly patients with
      atherosclerotic disease, even those who are in the improvement phase. Conclusion
      Unexpected sudden death by infectious aortitis in the recovery phase of
      antecedent infection.

PMID- 29321405
TI  - Reversible Parkinsonism and Multiple Cerebral Infarctions after Pulmonary
      Endarterectomy in a Patient with Antiphospholipid Syndrome.
AB  - Antiphospholipid syndrome (APS) is a cause of chronic thromboembolic pulmonary
      hypertension (CTEPH) and it is associated with an increased risk of postoperative
      neurological complications. We experienced a case of reversible parkinsonism
      after pulmonary endarterectomy (PEA) and subsequent multiple cerebral infarctions
      under standard anticoagulation therapy in a patient with CTEPH associated with
      APS. Strict management using a combination of antiplatelet and anticoagulation
      therapy should be considered in patients with a high titer of triple
      antiphospholipid antibodies in the perioperative period. We should be aware of
      the high risk of postoperative neurologic manifestations in patients with APS.

PMID- 29321406
TI  - An Acute Case of Granulomatous Amoebic Encephalitis-Balamuthia mandrillaris
      Infection.
AB  - A 74-year-old woman who exhibited drowsiness was referred to our hospital.
      Enhanced head magnetic resonance imaging (MRI) revealed multiple ring-enhancing
      lesions and lesions showing partial mild hemorrhaging. The patient gradually
      progressed to a comatose condition with notable brain deterioration of unknown
      cause on follow-up MRI. On day nine, the patient inexplicably died, although
      brain herniation was suspected. Autopsy and histopathology revealed numerous
      amoebic trophozoites in the perivascular spaces and within the necrotic tissue.
      Brain immunostaining tested positive for Balamuthia mandrillaris. Infection due
      to free-living amoeba is rare in Japan; however, it may increase in the near
      future due to unknown reasons.

PMID- 29321407
TI  - Vertebral Osteomyelitis Caused by Helicobacter cinaedi Identified Using Broad
      range Polymerase Chain Reaction with Sequencing of the Biopsied Specimen.
AB  - A 65-year-old man presented with gradually exacerbating low back pain. Magnetic
      resonance imaging revealed vertebral osteomyelitis in the Th11-L2 vertebral
      bodies and discs. The patient showed negative findings on conventional cultures.
      Direct broad-range polymerase chain reaction (PCR) with sequencing of the
      biopsied specimen had the highest similarity to the 16S rRNA gene of Helicobacter
      cinaedi. This case suggests that direct broad-range PCR with sequencing should be
      considered when conventional cultures cannot identify the causative organism of
      vertebral osteomyelitis, and that this method may be particularly useful when the
      pathogen is a fastidious organism, such as H. cinaedi.

PMID- 29321408
TI  - The Factors Affecting the Non-dipper Pattern in Japanese Patients with Severe
      Obstructive Sleep Apnea.
AB  - Objective Obstructive sleep apnea (OSA) is assumed to influence the circadian
      blood pressure (BP) fluctuation, particularly causing nocturnal hypertension and
      changing the dipping pattern of nocturnal BP. This study aimed to clarify the
      triggers of the non-dipper pattern in nocturnal BP in Japanese patients with
      severe OSA (the apnea-hypopnea index >=30/h). Methods Of 541 patients with OSA
      diagnosed using polysomnography (PSG) and ambulatory BP monitoring (ABPM), 163
      patients <60 years of age (Younger group) and 101 patients >=60 years of age
      (Older group) were stratified into the dipper or non-dipper pattern groups.
      Results A logistic regression analysis was performed using a non-dipper pattern
      as a dependent variable. A multivariate analysis demonstrated that the cumulative
      percentage of time at saturation below 90% was the only independent risk factor
      for the non-dipper and riser patterns in the Younger group (odds ratio, 1.022;
      95% confidence interval, 1.001-1.044; p=0.035), whereas slow-wave sleep (odds
      ratio, 0.941; 95% confidence interval, 0.891-0.990; p=0.019) and the use of
      angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers
      (odds ratio, 2.589; 95% confidence interval, 1.051-6.848; p=0.039) were risk
      factors in the Older group. Conclusion These findings suggested that the degree
      of desaturation in young OSA patients and sleep quality in old OSA patients might
      influence the dipping patterns in nocturnal BP.

PMID- 29321409
TI  - Pulmonary Embolism Caused by Intravenous Leiomyosarcoma of the Lower Limb.
AB  - Pulmonary embolism (PE) is usually caused by thrombosis or tumor. We report the
      long-term survival of a patient with PE due to a leiomyosarcoma in the deep vein.
      A 71-year-old woman complained of dyspnea and swelling of the left lower limb.
      Computed tomography revealed filling defects in the pulmonary arteries and deep
      vein. She was diagnosed with PE caused by venous thrombosis and treated with
      anticoagulant therapy. Her symptoms were prolonged, and D-dimer tests remained
      negative. Biopsy of the substance in the deep vein revealed leiomyosarcoma. The
      possibility of PE caused by extravascular or intravascular tumors should be
      considered when a patient is negative for D-dimer.

PMID- 29321410
TI  - Successful Management of Pregnancy in a Patient with Systemic Lupus Erythematosus
      associated Pulmonary Arterial Hypertension.
AB  - Pregnancy in women with systemic lupus erythematosus (SLE)-associated pulmonary
      arterial hypertension (PAH) remains a high risk. We successfully managed a
      pregnancy in a patient with SLE-PAH. A 31-year-old pregnant woman with SLE-PAH
      had worsening PAH and SLE flare-up during pregnancy and a sudden increase in
      pulmonary arterial pressure after delivery. SLE-PAH was controlled by continuous
      intravenous epoprostenol and inhaled nitric oxide therapy combined with high-dose
      corticosteroids under close hemodynamic monitoring. Women with SLE-PAH should
      avoid pregnancy. However, in case of a similar event, we recommend our case as a
      good reference for improving the outcome of pregnancy with SLE-PAH.

PMID- 29321411
TI  - Cough Headache Presenting with Reversible Cerebral Vasoconstriction Syndrome.
AB  - Cough headache can be a primary benign condition or secondary to underlying
      etiologies. We herein describe a case of a 52-year-old woman with cough headache
      that presented as reversible cerebral vasoconstriction syndrome (RCVS). Some
      cases of RCVS are caused by an aberrant sympathetic response to activities that
      cause an intracranial pressure surge. Therefore, cough headache should be
      recognized as a possible presentation of RCVS, even without thunderclap headache
      or neurological deficits.

PMID- 29321412
TI  - The Successful Treatment of Sodium Polystyrene Sulfonate-induced Enteritis
      Diagnosed by Small Bowel Endoscopy.
AB  - Sodium polystyrene sulfonate (SPS: Kayexalate(r)) is an ion-exchange resin used
      to treat hyperkalemia in patients with chronic kidney disease. It is known that
      this resin sometimes causes colonic necrosis and perforation, but there are few
      reports about small bowel necrosis associated with SPS. We herein report the case
      of a patient who developed SPS-induced small bowel necrosis, which was diagnosed
      based on the examination of a small bowel endoscopic biopsy specimen. The SPS
      induced small bowel necrosis was resistant to conservative treatment including
      the cessation of SPS, and finally required surgical bowel resection.

PMID- 29321413
TI  - Remission of Refractory Ascites and Discontinuation of Hemodialysis after
      Additional Rituximab to Long-term Glucocorticoid Therapy in a Patient with TAFRO
      Syndrome.
AB  - Thrombocytopenia, ascites, myelofibrosis, renal dysfunction, and organomegaly
      (TAFRO) syndrome is a newly recognized but rare disease, and its treatment has
      not yet been established. We reported a 50-year-old woman with TAFRO syndrome
      diagnosed 2 years after the initial symptoms of a fever, fatigue, epigastric
      pain, edema, ascites, lymphadenopathy, thrombocytopenia and renal insufficiency.
      The patient showed refractory ascites and required hemodialysis under
      corticosteroid mono-therapy for suspected immune-mediated disease but was
      successfully treated with additive rituximab, resulting in improvement in her
      laboratory data, the withdrawal of hemodialysis and the disappearance of ascites.
      This case underscores the therapeutic utility of rituximab in patients with
      corticosteroid-resistant TAFRO syndrome, even long after the onset of the
      disease.

PMID- 29321416
TI  - Simultaneous Nontraumatic Spinal and Intracranial Subdural Hematoma.

PMID- 29321415
TI  - Cerebral Toxoplasmosis Diagnosed by Nested-polymerase Chain Reaction in a Patient
      with Rheumatoid Arthritis.
AB  - A 65-year-old woman with rheumatoid arthritis (RA) visited our hospital because
      of right facial sensory hypoesthesia. Cerebral toxoplasmosis was suspected on
      brain magnetic resonance imaging. We discontinued methotrexate for RA and started
      a sulfamethoxazole/trimethoprim (ST) mixture. Although ST treatment was
      interrupted because of adverse reactions, her prognosis was favorable. The
      Toxoplasma 18S rDNA gene was detected by nested-polymerase chain reaction (PCR)
      from blood and cerebrospinal fluid. Detecting the Toxoplasma 18S rDNA gene by
      nested-PCR is useful for the diagnosis and safer than a brain biopsy. In
      addition, the discontinuation of immunosuppressants may be recommended in
      patients compromised by those immunosuppressants.

PMID- 29321414
TI  - The Platelet Count Can Predict In-hospital Death in HIV-negative Smear-positive
      Pulmonary Tuberculosis Inpatients.
AB  - Objective This retrospective cohort study investigated whether the three
      components of the blood cell count have prognostic implications in HIV-negative
      Japanese adult inpatients with smear-positive pulmonary tuberculosis. Methods We
      reviewed patients who were treated by the isoniazid, rifampicin, pyrazinamide,
      and ethambutol regimen or by the isoniazid, rifampicin, and ethambutol regimen.
      The association between the patient data on admission and the survival outcome
      was evaluated. Results We reviewed 367 consecutive patients (male, 60.5%) with a
      median age of 72 [interquartile range (IQR), 54-82] years. While the white blood
      cell count did not differ between the two groups, (discharged alive: 7,000/MUL;
      IQR, 5,500-9,300; died in hospital: 7,200/MUL; IQR, 5,600-9,400; p=0.797),
      hemoglobin level (discharged alive: 11.5 g/dL; IQR, 10.0-13.1; died in hospital:
      9.9 g/dL; IQR, 8.6-11.3; p<0.001) and the platelet count (discharged alive:
      275,000/MUL; IQR, 206,000-345,000; died in hospital: 149,000/MUL; IQR, 93,000
      236,000; p<0.001) were lower in patients who died in hospital. After dividing
      patients into hemoglobin- and platelet-based quantiles, the lower quantile class
      tended to show poorer survival (log-rank test for trend p<0.001 for both). A
      multi-variable Cox proportional hazards model revealed that hazard ratio for in
      hospital death for every 1,000/MUL increase of platelet count was 0.997 (95%CI,
      0.995-0.999; p=0.010); the hazard ratio for the hemoglobin level was not
      significant. Conclusion A low platelet count was clearly related to a poor life
      prognosis in HIV-negative Japanese adult inpatients with smear-positive pulmonary
      tuberculosis.

PMID- 29321418
TI  - Optimal Medications and Appropriate Implantable Cardioverter-defibrillator Shocks
      in Aborted Sudden Cardiac Death Due to Coronary Spasm.
AB  - Objective Life-threatening ventricular arrhythmias are recognized in patients
      with coronary spastic angina. Implantable cardioverter-defibrillators (ICDs) are
      effective in patients with structural heart disease and ventricular fibrillation.
      However, the optimal medication for patients with aborted sudden cardiac death
      (SCD) due to coronary artery spasm after the implantation of ICD remains
      controversial. Methods We investigated the medications and the numbers of
      appropriate ICD shocks in 137 patients with a history of aborted SCD due to
      coronary spasm. Results Appropriate ICD shocks were observed in 24.1% (33/137) of
      patients with aborted SCD due to coronary spasm during 41 months of follow-up.
      Only 15 (15.6%) of the 96 patients with ICDs received aggressive medical therapy,
      including two or three calcium-channel antagonists. The rate of appropriate ICD
      shocks was significantly higher in Western countries than in Asian countries
      (42.9% vs. 19.3%, p<0.01), whereas the medications did not differ between the two
      regions. Appropriate ICD shocks successfully resuscitated 33 patients. Three
      patients died due to second serious fatal arrhythmias. Conclusion Appropriate ICD
      shocks were recognized in a quarter of patients with aborted SCD due to coronary
      spasm and ICD implantation was effective for suppressing the next serious fatal
      arrhythmia in these patients. We should reconsider prescribing more medications
      after ICD implantation in patients with aborted SCD due to coronary artery spasm.

PMID- 29321417
TI  - Peripheral Ulcerative Keratitis Associated with Granulomatosis with Polyangiitis
      Emerging Despite Cyclophosphamide, Successfully Treated with Rituximab.
AB  - A 67-year-old Japanese man was diagnosed with granulomatosis with polyangiitis
      based on the presence of right maxillary sinusitis, proteinase 3 antineutrophil
      cytoplasmic antibody positivity, and right scleritis. A conjunctival biopsy
      specimen showed neutrophil-predominant infiltration around the vessels without
      granuloma. Because there was a risk of blindness, pulsed methylprednisolone and
      intravenous cyclophosphamide pulse therapy (IVCY) were started. However, it was
      ineffective, and peripheral ulcerative keratitis newly emerged. We promptly
      switched the treatment from IVCY to rituximab, and ophthalmologists performed
      amniotic membrane transplantation, which avoided blindness. The close and
      effective working relationship between physicians and ophthalmologists improved
      our patient's ocular prognosis.

PMID- 29321419
TI  - Useful Predictive Factors for Bacteremia among Outpatients with Pyelonephritis.
AB  - Objective The aim of this study was to identify predictive factors for bacteremia
      conveniently and quickly among outpatients diagnosed with pyelonephritis.
      Patients All patients who were diagnosed with pyelonephritis at the outpatient
      clinic in the Department of General Medicine of Juntendo University Hospital from
      April 1, 2008, to June 30, 2015, were enrolled. Patients from whom blood cultures
      had not been taken were excluded. Methods Clinical information was extracted from
      medical charts. Factors potentially predictive of bacteremia were analyzed using
      a t-test and Fisher's exact test, followed by a multivariable logistic regression
      model analysis. Results Blood cultures were drawn from 116 patients, and 25 (22%)
      presented with bacteremia. A multivariate analysis with the age, chills, platelet
      count and urine nitrite test results revealed that older age, positive urinary
      nitrite test results and chills tended to be associated with bacteremia,
      respectively. [older age: unit odds ratio (OR) 1.02, p=0.052, 95% confidence
      interval (CI) 1.00-1.05, positive urinary nitrite test findings: OR 2.5, p=0.092,
      95% CI 0.86-7.7, chills: OR 2.5, p=0.096, 95% CI 0.84-7.65]. The area under the
      receiver operating characteristic (ROC) curve of this model was 0.77. Regardless
      of age, positive urinary nitrite test findings were significantly associated with
      bacteremia (OR 3.1, p=0.033, 95% CI 1.1-9.2), and chills tended to be associated
      with bacteremia (OR 2.7, p=0.07, 95% CI 0.93-7.9) The area under the ROC curve of
      this model was 0.75. Conclusion Bacteremia should be considered in pyelonephritis
      patients with rapidly assessable factors in outpatient clinic. In particular, a
      model including a urinary nitrite test has the potential to aid in the prediction
      of bacteremia.

PMID- 29321420
TI  - Validity of the Pre-endoscopic Scoring Systems for the Prediction of the Failure
      of Endoscopic Hemostasis in Bleeding Gastroduodenal Peptic Ulcers.
AB  - Objective Although several pre-endoscopic scoring systems have been used to
      predict the mortality or the need for intervention for upper gastrointestinal
      bleeding, their usefulness to predict the failure of endoscopic hemostasis in
      bleeding gastroduodenal peptic ulcers has not yet been fully investigated. In
      this study, we evaluated the usefulness of the Glasgow-Blatchford score (GBS),
      the clinical Rockall score (CRS), and the AIMS65 score in predicting the failure
      of endoscopic hemostasis in patients with bleeding gastroduodenal peptic ulcers.
      Methods We retrospectively evaluated 226 consecutive emergency endoscopic cases
      with bleeding gastroduodenal peptic ulcers between April 2010 and September 2016.
      The study outcome was the failure of first endoscopic hemostasis. The GBS, CRS,
      and AIMS65 scores were assessed for their ability to predict the failure of
      endoscopic hemostasis using a receiver-operating characteristic curve. Results
      Eight cases (3.5%) failed to achieve first endoscopic hemostasis. Surgery was
      required in six cases, and interventional radiology was required in two cases.
      The GBS was superior to both the CRS and the AIMS65 score in predicting the
      failure of endoscopic hemostasis [area under the curve, 0.77 (95% confidence
      interval, 0.64-0.90), 0.65 (0.56-0.74) and 0.75 (0.56-0.95), respectively]. No
      failure of endoscopic hemostasis was noted in cases in which the patient scored
      less than GBS 10 and CRS 2. Conclusion The GBS was the most useful scoring system
      for the prediction of failure of endoscopic hemostasis in patients with bleeding
      gastroduodenal peptic ulcers. The GBS was also useful in identifying the patients
      who did not require surgery or interventional radiology.

PMID- 29321421
TI  - A Fatal Case of Super-super Obesity (BMI >80) in a Patient with a Necrotic Soft
      Tissue Infection.
AB  - A 35-year-old man (height, 169 cm; body weight, 240 kg; BMI, 84) visited the
      Department of Dermatology due to left leg pain and swelling. Focused enhanced
      computed tomography (CT) of the left leg ruled out complications of deep venous
      thrombosis. Surgical exploration of the left leg resulted in a diagnosis of
      necrotic soft tissue infection, but amputation was ruled out due to his weight.
      The patient ultimately died of multiple organ failure on the fourth day of
      hospitalization. A culture of the surgical material revealed Streptococcus
      dysgalactiae. The present case suggests that super-obese patients should be
      aggressively treated before lethal complications occur.

PMID- 29321422
TI  - Progressive Restrictive Ventilatory Impairment in Idiopathic Diffuse Pulmonary
      Ossification.
AB  - Diffuse pulmonary ossification (DPO) is a rare disease characterized by
      metaplastic bone formation in the lung. There are few reports with a long-term
      follow-up of this disease. We herein report a 47-year-old man diagnosed with
      idiopathic DPO at 30 years of age. The patient's vital capacity was normal until
      36 years of age (3.39 L, 82.4% predicted), but it was severely decreased when he
      visited the hospital again at 47 years of age due to cough and dyspnea (1.98 L,
      44.6% predicted). Chest computed tomography showed a significant increase in the
      number of high-density nodules, suggesting that the progression of DPO had caused
      restrictive ventilatory impairment.

PMID- 29321423
TI  - Constrictive Pericarditis as a Long-term Undetermined Etiology of Ascites and
      Edema.
AB  - Constrictive pericarditis (CP) is defined as impedance to diastolic filling
      caused by a fibrotic pericardium. The diagnosis of CP is a clinical challenge and
      requires a high index of clinical suspicion. The signs and symptoms of CP include
      fatigue, edema, ascites, and liver dysfunction. These can be mistakenly diagnosed
      as primary liver disease. We present the case of a 69-year-old woman with a 7
      year history of leg edema and a 2-year history of ascites who was initially
      diagnosed with cryptogenic liver cirrhosis and was finally diagnosed with CP.

PMID- 29321425
TI  - Elevation of Plasmin-alpha2-plasmin Inhibitor Complexes in Patients with AL
      Amyloidosis.

PMID- 29321424
TI  - Anti-MuSK Antibody-positive Myasthenia Gravis Successfully Treated with
      Outpatient Periodic Weekly Blood Purification Therapy.
AB  - A 37-year-old man with anti-muscle-specific tyrosine kinase (MuSK) antibody
      positive myasthenia gravis (MG) presented with subacute progressive dysphagia and
      muscle weakness of the neck and bilateral upper extremities. Conventional immune
      suppressive treatments and high-dose intravenous immunoglobulin were ineffective.
      He then displayed repeated exacerbations and remissions over the course of two
      years, despite two to four sessions of plasma exchange (PE) every two months. The
      patient was successfully treated with outpatient periodic weekly blood
      purification therapy with alternative PE and double-filtration plasmapheresis
      using an internal shunt. This case report suggests the benefits of blood
      purification therapy with an internal shunt against anti-MuSK antibody-positive
      MG.

PMID- 29321426
TI  - Percutaneous Coronary Intervention for a Patient with Left Main Coronary
      Compression Syndrome.
AB  - Left main coronary compression syndrome rarely occurs in patients with severe
      pulmonary hypertension. A 65-year-old woman with severe pulmonary hypertension
      due to an atrial septal defect suffered from angina on effort. Cardiac computed
      tomography and coronary angiography revealed considerable stenosis of the left
      main coronary artery (LMA) caused by compression between the dilated main
      pulmonary artery trunk and the sinus of valsalva. Stenting of the LMA under
      intravascular ultrasound imaging was effective for the treatment of angina. We
      herein report the diagnosis and management of this condition with a brief
      literature review.

PMID- 29321427
TI  - Cardiac Sarcoidosis Concomitant with Large-vessel Aortitis Detected by 18F
      fluorodeoxyglucose Positron Emission Tomography.
AB  - We herein report a case of concurrent cardiac sarcoidosis and large-vessel
      aortitis detected by 18F-fluorodeoxyglucose positron emission tomography (FDG
      PET) and followed up during immunosuppressive therapy. After high-dose
      prednisolone administration (1 mg/kg), serial FDG-PET showed that almost all of
      the abnormal FDG uptake in the heart and extracardiac region, including the
      abdominal to bilateral iliac arteries, had been disappeared. During the tapering
      of prednisolone, additive methotrexate therapy was needed to treat the recurrence
      of cardiac sarcoidosis. FDG-PET is a useful tool for detecting cardiac
      sarcoidosis concomitant with large-vessel aortitis and monitoring the
      effectiveness of immunosuppressive therapy.

PMID- 29321428
TI  - Synchronous Occurrence of Mycosis Fungoides, Diffuse Large B Cell Lymphoma and
      Acute Myeloid Leukemia.
AB  - Patients with mycosis fungoides (MF), the most common subtype of primary
      cutaneous T-cell lymphoma, have an increased risk of developing secondary
      malignancies. We herein report two rare cases of MF concurring with diffuse large
      B cell lymphoma (B lymphoid lineage) and acute myeloid leukemia (myeloid lineage)
      in two otherwise healthy elderly patients. Potential etiologic factors, including
      the impact of the therapy-associated inflammatory response on the development of
      secondary tumors in patients with MF, are discussed. Further clinical,
      experimental and genetic studies are needed to elucidate possible
      physiopathogenic associations among the three concurrent malignancies occurring
      in the cases presented here.

PMID- 29321429
TI  - Early Combination Therapy with Corticosteroid and Nucleoside Analogue Induces
      Rapid Resolution of Inflammation in Acute Liver Failure due to Transient
      Hepatitis B Virus Infection.
AB  - Objective Patients with acute hepatitis B sometimes develop acute liver failure
      (ALF), which has a poor prognosis. The efficacy of nucleoside analogue (NA)
      monotherapy for ALF due to transient hepatitis B virus infection (HBV-ALF)
      remains controversial. Further investigations are necessary in nations with a
      shortage of donor livers for liver transplantation. In the present study, we
      aimed to clarify the efficacy of combination therapy with corticosteroid (CS) and
      NA in the treatment HBV-ALF. Patients We examined the clinical and biochemical
      features of 19 patients with HBV-ALF who were treated in the early stage of the
      disease between 2000 and 2015. Results Fourteen patients received CS and NA (CS +
      NA group) and 5 received NA monotherapy (NA group). Eleven patients (58%)
      survived and 8 (42%) died. The survival rates in the CS + NA and NA groups were
      64% and 40%, respectively (p=0.60). The mean alanine aminotransferase (ALT)
      levels declined significantly at week 2 in both groups. The mean PT activities
      improved significantly at weeks 1 and 2 in the CS + NA group (p<0.05) but not in
      the NA group. None of the surviving patients developed persistent infection.
      Conclusion Combination therapy with CS and NA induces the rapid resolution of
      inflammation leading to a rapid recovery of the liver function. When it is
      administered at a sufficiently early stage, it would have a survival benefit and
      prevent persistent infection in HBV-ALF.

PMID- 29321430
TI  - New-onset Takayasu's Arteritis as Acute Myocardial Infarction.
AB  - We herein report the case of a 25-year-old Japanese woman with left-main-trunk
      acute myocardial infarction (LMT-AMI). She had cardiogenic shock, so emergency
      percutaneous intervention was performed. Intravascular ultrasound of LMT-AMI
      showed that the three-layered structure of the intima, tunica media, and
      adventitia was not clearly visible, and the vessel was concentrically thickened;
      unstable plaque and calcification were not seen. AMI is rarely seen in young
      women, but Takayasu's arteritis is one major cause. If a young woman complaining
      of typical chest pain as acute coronary syndrome is encountered, systemic
      diseases must be considered.

PMID- 29321431
TI  - Self-reported Slower Eating Is Associated with a Lower Salt Intake: A Population
      based Cross-sectional Study.
AB  - Objective Evidence suggests that the eating rate is positively associated with
      the body weight and blood pressure. Furthermore, people who are overweight or
      obese tend to have higher salt intakes than those of normal weight. To
      investigate whether or not the eating rate is also associated with the salt
      intake, a cross-sectional study was conducted using health examination survey
      data collected in 2014 from 7,941 residents of Sado City, Niigata, Japan. Methods
      The eating rates were evaluated using a questionnaire; 11.7% of participants
      rated themselves as slow eaters, 65.6% as normal eaters, and 22.7% as fast
      eaters. The salt intake was estimated from sodium and creatinine spot urine
      measurements using Tanaka's formula. Associations with eating rate were evaluated
      using multivariate linear regression analyses, with normal eaters as the
      reference (set at 0). Results Self-reported eating rates were positively
      associated with the salt intake after adjustment for age and sex [beta
      coefficient (95% confidence interval) for slow -0.51 (-0.67, -0.35); fast 0.18
      (0.05, 0.30) ]. Further adjustment for the body mass index showed that slower
      eaters had lower salt intakes than normal eaters, but there was no marked
      difference in the salt intake between normal and fast eaters. The association
      between slower eating and a lower salt intake persisted after further adjustment
      for comorbidities [slow -0.33 (-0.49, -0.18) ]. Conclusion Our results suggest
      that reducing eating rates may be an effective strategy for reducing dietary salt
      intake as well as preventing obesity.

PMID- 29321432
TI  - Acute-onset Autoimmune Hepatitis in a Young Woman with Type 1 Diabetes Mellitus.
AB  - Autoimmune hepatitis (AIH) and type 1 diabetes mellitus (T1DM) are thought to be
      induced by autoimmunity, but their coexistence has rarely been reported. We
      herein report a case in which a patient with T1DM developed acute-onset AIH. A 26
      year-old woman, who had been diagnosed with T1DM in childhood, was transferred to
      our hospital because of acute liver failure of unknown etiology. The
      administration of corticosteroids including steroid pulse therapy was effective.
      Based on the histological finding of massive centrilobular necrosis and a good
      response to steroid therapy, we diagnosed the patient with acute-onset AIH. This
      case indicates that AIH can occur in young T1DM patients.

PMID- 29321435
TI  - Chronic Expanding Hematoma on the Chest Wall after Mastectomy.

PMID- 29321433
TI  - CV2/CRMP5-antibody-related Paraneoplastic Optic Neuropathy Associated with Small
      cell Lung Cancer.
AB  - A 61-year-old woman who had smoked for 41 years developed subacute dizziness,
      ataxic gait, opsoclonus, and right visual impairment. She had right optic disc
      swelling and optic nerve gadolinium enhancement on magnetic resonance imaging.
      She had small-cell lung cancer (SCLC), with CV2/collapsin response mediator
      protein (CRMP) 5 and HuD antibodies in her serum and cerebrospinal fluid. She was
      diagnosed with paraneoplastic optic neuropathy (PON) accompanied by
      paraneoplastic opsoclonus-ataxia syndrome. Her symptoms improved after removing
      the SCLC. Classical PON is rare in Japan. We recommend assaying for CV2/CRMP5
      antibodies and searching for cancer in elderly patients with subacute painless
      visual impairment.

PMID- 29321434
TI  - Tricuspid and Mitral Valve Regurgitation with Bi-fascicular Block Following a
      Horse Kick.
AB  - A 40-year-old man was transferred to our hospital following an isolated horse
      kick injury to the anterior chest wall. The case showed bi-fascicular block,
      severe tricuspid valve regurgitation due to ruptured chordae tendineae of the
      anterior leaflet, moderate mitral valve regurgitation due to prolapse of mitral
      anterior leaflet, and hypokinetic motion of the inferior septal wall. Both
      tricuspid and mitral insufficiency were completely repaired by a surgical
      operation. Fortunately, these injuries were not fatal in this case, but the
      comprehensive assessment of cardiac damage and careful observation are important
      for managing patients with cardiac injury.

PMID- 29321436
TI  - Necrotizing Sarcoid Granulomatosis with Natural Resolution after a Surgical Lung
      Biopsy.
AB  - Necrotizing sarcoid granulomatosis (NSG) is a rare disease that is diagnosed
      based on pathological findings. We herein report the case of a 27-year-old man
      who had multiple nodular shadows in bilateral lung fields on chest radiography
      and elevated levels of C-reactive protein (CRP). The pathological evaluation of a
      lung biopsy specimen showed the infiltration of lymphocytes, granulomas with
      necrosis and granulomatous angiitis. He was therefore diagnosed with NSG. He has
      been followed without treatment, as his fever and CRP levels decreased
      immediately after the surgical lung biopsy. Thereafter, the pulmonary nodular
      shadows gradually recovered without any treatment within a few months. Our
      experience suggests the possibility that surgical invasion might trigger an
      improvement in disease activity.

PMID- 29321437
TI  - Esophageal Granular Cell Tumors Can Be Differentiated from Leiomyomas Using
      Endoscopic Ultrasonography.
AB  - Objective Although esophageal granular cell tumors have been reported to present
      as hypoechoic tumors, we noticed that their echogenicity is similar to that of
      the submucosal layer. We investigated the sonographic features of esophageal
      granular cell tumors and the diagnostic accuracy of the features. Methods Seven
      patients with esophageal granular cell tumors who underwent endoscopic
      ultrasonography were retrospectively reviewed. Thirteen patients with esophageal
      leiomyoma were selected as historical control subjects. The brightness of the
      tumor on ultrasonography images was measured and the echogenicity was
      standardized according to the echogenicity of the proper muscle and submucosal
      layers. Ten board-certified endoscopists then independently evaluated the
      endoscopic pictures of the 20 patients (Test 1), as well as the endoscopic
      ultrasonography images together with endoscopic pictures of the same patient set
      (Test 2). Results The standardized echogenicity in granular cell tumors was
      significantly higher than that in leiomyomas. The diagnostic accuracy of the 10
      evaluators using endoscopic pictures alone (Test 1) was 72.0%. The addition of
      endoscopic ultrasonography images (Test 2) significantly improved the accuracy to
      93.0%. Conclusion The echogenicity of granular cell tumors was similar to that of
      the submucosal layer, and it was significantly higher than that of leiomyomas.
      Endoscopic ultrasonography images facilitate the accurate identification of
      esophageal granular cell tumors.

PMID- 29321438
TI  - Vogt-Koyanagi-Harada Disease Associated with Influenza A Virus Infection.
AB  - We herein report a case of a 31-year-old Japanese man who simultaneously had a
      positive influenza A virus antigen test result and Vogt-Koyanagi-Harada disease
      (VKHD), demonstrated by both diffuse multiple early hyperfluorescent points on
      fluorescein fundus photography and serous retinal detachments on optical
      coherence tomography. He had meningitis. It was difficult to determine whether
      the main cause of meningitis was influenza A or VKHD. After initial treatment
      with peramivir for influenza A and then methylprednisolone pulse with subsequent
      corticosteroid therapy for VKHD, his symptoms improved gradually. These findings
      suggest that influenza A virus infection contributes to the onset or exacerbation
      of VKHD.

PMID- 29321439
TI  - The Association of Bite Instability and Comorbidities in Elderly People.
AB  - Objective The purpose was to evaluate the association between bite instability
      and comorbidities, comprehensive geriatric evaluations, or disabilities in
      elderly people. Methods A dentist examined the oral function, such as the bite
      stability, number of teeth, and the use of dentures, in 119 patients (93 women,
      mean age: 86.7+/-7.8) in 2 nursing homes for the elderly. The association between
      the oral function and the prevalence of diseases, including hypertension,
      diabetes mellitus, and dementia, was analyzed. Results The median number of teeth
      was 0 [0, 4]. The patients were divided into a bite-stable group (n=78, 66%) and
      bite-unstable group (n=41, 34%). The prevalence of hypertension was significantly
      higher in the bite-stable group than in the bite-unstable group (83% vs. 63%,
      respectively; p=0.0149), whereas the prevalence of diabetes mellitus was
      significantly lower in the bite-stable group than in the bite-unstable group (10%
      vs. 27%, respectively; p=0.0190). The prevalence of a cognitive function decline
      was significantly lower in the bite-stable group as well (59% vs. 83%, p=0.0082).
      According to the simplified comprehensive geriatric assessment 7, the bite-stable
      group scored significantly higher for instrumental activities of daily living
      (ADL) than the bite-unstable group (54% vs. 24%, respectively; p=0.0021). A
      multivariate logistic regression analysis demonstrated that bite instability was
      independently correlated with hypertension, diabetes mellitus, and instrumental
      activities of daily living. Conclusion Bite instability was independently
      associated with a decreased prevalence of hypertension or increased prevalence of
      diabetes mellitus and low levels of instrumental ADL in the elderly.

PMID- 29321440
TI  - An Overview of Kidney Disease Following Hematopoietic Cell Transplantation.
AB  - Hematopoietic stem cell transplantation (SCT) recipients are exposed to a large
      amount of anti-cancer drugs, immunosuppressors, and irradiation during the peri
      SCT period. Thus, they have to overcome serious adverse events related to
      unavoidable but toxic procedures, including organ disorders. In particular, acute
      kidney injury (AKI) is one of the most critical complications, because it
      influences the mortality of patients. A few patients who survive AKI may develop
      nephrotic syndrome, and precedent AKI is also closely associated with chronic and
      progressive loss of the renal function in post-SCT patients. These kidney
      diseases place a heavy burden on SCT patients, both medically and economically.
      Therefore, hematologists who evaluate SCT should be fully aware of the
      development of these kidney diseases after SCT. We herein review the common
      course of kidney disease development following allogeneic SCT to provide
      healthcare professionals with practical information on renal disease in SCT
      patients.

PMID- 29321442
TI  - Acquired von Willebrand Syndrome due to Aortic Valve Stenosis in a Case with
      Antiphospholipid Antibody.
AB  - Acquired von Willebrand syndrome (AVWS) is a bleeding disorder caused by an
      acquired deficiency of von Willebrand factor (vWF). Some patients with AVWS show
      a low bleeding tendency and are diagnosed by the presence of a mild prolongation
      of activated partial thromboplastin time (APTT) preoperatively. Another cause of
      APTT prolongation is the presence of antiphospholipid antibody (aPL). We
      experienced a case of AVWS due to aortic valve stenosis in a patient with aPL in
      whom aortic valve replacement surgery was successful with vWF replacement. In
      patients with AVWS-associated disorders who are identified based on APTT
      prolongation at the preoperative examination, both vWF and aPL screening tests
      must be performed.

PMID- 29321441
TI  - Diabetes Mellitus Prevents an Improvement in the Serum Albumin Level During
      Interferon-free Sofosbuvir-based Therapy for Chronic Hepatitis C Patients: A
      Multi-institutional Joint Study.
AB  - Objective Interferon-free regimens of direct-acting antiviral agents have
      improved the treatment response for chronic hepatitis C virus (HCV) infection,
      and improvement in the serum albumin level during interferon-free therapy has
      been reported. The aim of this study was to identify the factors that influence
      the improvement in the serum albumin level in patients receiving interferon-free
      antiviral therapy. Methods This retrospective, multicenter study consisted of 471
      Japanese patients with chronic hepatitis and compensated liver cirrhosis infected
      with HCV who completed 12-week interferon-free sofosbuvir (SOF)-based therapy
      [SOF plus ledipasvir for genotype 1 (n=276) and SOF with ribavirin for genotype 2
      (n=195)]. We evaluated the changes in the serum albumin level from baseline to
      the end of treatment (DeltaAlb). Results When compared with the normal-albumin
      group (baseline serum albumin >35 g/L, n=406), the low-albumin group (baseline
      serum albumin <=35 g/L, n=65) showed a significant increase in the mean DeltaAlb
      (5.5 g/L vs. 1.0 g/L, p<0.001). In the low-albumin group, a multivariate logistic
      regression analysis extracted diabetes mellitus as a negative predictive factor
      of median DeltaAlb >5.0 g/L (odds ratio: 0.19, 95% confidence interval: 0.048
      0.79, p=0.020). In the low-albumin group, the mean DeltaAlb was significantly
      lower in the diabetic patients (n=14) than in the non-diabetic patients (n=51)
      (3.9 g/L and 5.7 g/L, p=0.049). Conclusion Interferon-free SOF-based therapy
      significantly improved the serum albumin in the low-albumin group patients with
      chronic HCV infection. However, the improvement in the serum albumin level was
      significantly lower in the diabetic patients than in the non-diabetic patients.

PMID- 29321444
TI  - Agricultural aspects of radiocontamination induced by the Fukushima nuclear
      accident - A survey of studies by the Univ. of Tokyo Agricultural Dept. (2011
      2016).
AB  - Immediately after the Fukushima nuclear power plant accident, a team of 40-50
      researchers at the Graduate School of Agricultural and Life Sciences at the
      University of Tokyo began to analyze the behavior of radioactive materials in the
      fallout regions. The fallout has remained in situ and become strongly adsorbed
      within the soil over time. 137Cs was found to bind strongly to the fine clay,
      weathered biotite, and organic matter in the soil; therefore, it has not
      mobilized from mountainous regions, even after heavy rainfall. In farmland, the
      quantity of 137Cs in the soil absorbed by crop plants was small. The downward
      migration of 137Cs in soil is now estimated at 1-2 mm/year. The intake of 137Cs
      by trees occurred through the bark and not from the roots. This report summarizes
      the findings of research across a wide variety of agricultural specialties.

PMID- 29321443
TI  - A new arena in cardiac surgery: Pediatric coronary artery bypass surgery.
AB  - Prior to the 1970s, pediatric coronary artery bypass surgery (PCABS) was seldomly
      performed due to the lack of compelling surgical indications. The advent of
      coronary sequelae secondary to Kawasaki disease (KD) and the occurrence of
      coronary artery complications due to newly developed procedures, such as the
      arterial switch operation and early repair for intrinsic congenital coronary
      malformations, necessitated the development of PCABS. Because children grow
      rapidly and their life expectancy is very long, with increasing exercise
      capability requirements, the strategy for PCABS should differ from that for
      bypass surgery in adults. PCABS utilizing unilateral and bilateral internal
      thoracic arteries (ITA) has become the most reliable surgical method for children
      because of the distinct structure of ITAs being resistant to KD, growth potential
      according to the child's somatic growth and long-term patency without wall
      degeneration. This operation utilizing ITA grafts is now being performed
      worldwide and is referred to as the "Kitamura operation" for KD coronary
      sequelae. Notably, the use of vein grafts should be avoided in children.
      Likewise, this operation can now be successfully performed in infants using a
      surgical microscope, for congenital coronary disorders. Currently, PCABS with
      ITAs has been established as a new arena in cardiac surgery, following our
      initial attempts.

PMID- 29321447
TI  - Addendum to "Treatment of rheumatoid arthritis with biological agents - as a
      typical and common immune-mediated inflammatory disease".

PMID- 29321445
TI  - Negative regulation of B cell responses and self-tolerance to RNA-related lupus
      self-antigen.
AB  - The antibody response to RNA-related antigens such as Sm/RNP requires the
      endosomal RNA sensor TLR7, and this process is crucial in the development of
      systemic lupus erythematosus at least in animal models. The inhibitory B cell
      receptor CD72 is unique because it recognizes Sm/RNP and specifically inhibits
      the activation of Sm/RNP-reactive B cells by activating SH2-containing protein
      tyrosine phosphatase 1 (SHP-1). In the normal immune system, Sm/RNP-reactive B
      cells are tolerized by a unique mechanism that probably involves SHP-1. These
      self-reactive B cells appear in the peripheral lymphoid organs, differentiate
      into marginal zone B cells, and then undergo apoptosis without further maturation
      into plasma cells. Thus, CD72 is involved in the suppression of TLR7-mediated
      response to RNA in complexes with nuclear proteins that are resistant to
      nucleases, whereas free RNAs are degraded by nucleases before they encounter the
      endosomal RNA sensor.

PMID- 29321446
TI  - Chemical characteristics of hadal waters in the Izu-Ogasawara Trench of the
      western Pacific Ocean.
AB  - Vertical profiles of potential temperature, salinity, and some chemical
      components were obtained at a trench station (29 degrees 05'N, 142 degrees 51'E;
      depth = 9768 m) in the Izu-Ogasawara (Bonin) Trench in 1984 and 1994 to
      characterize the hadal waters below ~6000 m depth. We compared portions of both
      the 1984 and 1994 profiles with nearby data obtained between 1976 and 2013.
      Results demonstrated that the hadal waters had slightly higher potential
      temperature and nitrate and lower dissolved oxygen than waters at sill depths
      (~6000 m) outside the trench, probably due to the effective accumulation of
      geothermal heat and active biological processes inside the trench. The silicate,
      iron, and manganese profiles in 1984 showed slight but significant increases
      below ~6000 m depth, suggesting that these components may have been
      intermittently supplied from the trench bottom. Significant amounts of 222Rn in
      excess over 226Ra were detected in the hadal waters up to 2675 m from the bottom,
      reflecting laterally supplied 222Rn from the trench walls.

PMID- 29321448
TI  - Detection of Chlorine in a Non-aqueous Solution via Anodic Oxidation and a
      Photochemical Reaction.
AB  - In this study, we developed a new chlorine gas detection method using anodic
      oxidation and a photochemical reaction. Chlorine gas was temporarily solvated
      with an aprotic polar solvent having an extensive potential range in the positive
      direction, and the solvated chlorine molecule was detected by an anodic oxidation
      reaction. In addition, when combined with ultraviolet light irradiation, we could
      detect high sensitivity using the photochemical reaction.

PMID- 29321449
TI  - A Simple Paper-based Colorimetric Device for Rapid and Sensitive Urinary Oxalate
      Determinations.
AB  - In this work, a simple and inexpensive paper-based colorimetric device (cPAD) was
      developed for oxalate measurements. The colorimetric assay is based on the
      formation of formazan via the reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) by oxalate decarboxylase and formate
      dehydrogenase on the paper device. After the sample was spotted on the device,
      MTT changed color from yellow to purple, and the purple color intensity
      correlated with the oxalate concentration. The quantitative detection of oxalate
      ranged from 10 - 1000 MUM, with a linear equation, y = 0.0086x + 34.978, and a
      correlation coefficient (R2) = 0.9994. The detection limit was 10 MUM by the
      naked eye. The recoveries of oxalate spiked in artificial urine samples evaluated
      by our cPADs were in the range of 81 - 92%. This simple cPAD for rapid and
      sensitive oxalate determination should be useful for diagnostic urinary oxalate
      measurements for point-of-care monitoring.

PMID- 29321450
TI  - Microfluidic Paper-based Analytical Devices for Determination of Creatinine in
      Urine Samples.
AB  - Simple, low-cost and portable microfluidic paper-based analytical devices
      (MUPADs) for determination of creatinine in urine samples were developed. The
      methodology was based on Jaffe reaction between the creatinine and picric acid in
      alkaline conditions, generating a colorimetric creatinine-alkaline picrate
      complex. The product exhibits an orange color that is clearly visible on the
      MUPADs. The color intensity of the complex, which is indicative of the
      concentration of creatinine, is then quantitatively determined using ImageJ
      software. Various experimental parameters were optimized to achieve the best
      performance of the MUPADs. Under the optimum conditions, a wide linear range was
      obtained in the range of 0.2 - 1 mM with a limit of detection and limit of
      quantitation of 0.08 and 0.26 mM, respectively. The accuracy of the proposed
      method was in good agreement with the standard Jaffe method. Finally, the
      developed devices were successfully applied for the determination of creatinine
      in urine samples.

PMID- 29321451
TI  - Enzyme Chemotaxis on Paper-based Devices.
AB  - Microfluidics has served as a technology for the design and development of a
      myriad of devices owing to their reduced reagent consumption rate and short
      sampling-to-result time. Chemotaxis is the movement of materials, particularly
      biological species, in response to the influence of chemical stimulation. Herein,
      we describe, for the first time, chemotactic behavior on a microfluidic paper
      based analytical device (MUPAD) to afford a distribution of products not
      obtainable under other (non-MUPAD) experimental conditions using as a model
      enzyme-substrate system glucose oxidase (GOx) and glucose. MUPADs are easily
      fabricated by patterning hydrophobic materials in hydrophilic paper. They are low
      cost, compatible with biological samples, and have shown promise as platforms for
      various applications and in resource-limited settings.

PMID- 29321453
TI  - Nanomaterial-functionalized Cellulose: Design, Characterization and Analytical
      Applications.
AB  - Cellulose-nanomaterial hybrid systems are promising platforms for the development
      of portable devices that can be used for fast and inexpensive analysis in the
      clinical, environmental and food monitoring fields. By combining the chemical and
      physical properties of the cellulosic network with the unique optical, electrical
      and catalytic functions of nanomaterials, it is possible to create versatile
      devices with engineered sensing functions. This review describes the most
      commonly used types of nanomaterials, their unique properties and assembly in
      hybrid structures in conjunction with cellulose paper and provides an overview of
      the most commonly used detection methodologies and their performance for selected
      applications. Finally, future perspectives and challenges to the implementation
      of these devices for real world applications are discussed, with focus on method
      optimization, validation and regulation in order to reach consumers.

PMID- 29321454
TI  - Paper-like Surface Microstructure Fabricated on a Polymer Surface by Femtosecond
      Laser Machining.
AB  - In this study, we demonstrate the precise control of fluid flow using femtosecond
      (FS) laser-induced microstructures. A microgroove structure inscribed on a
      poly(methyl methacrylate) (PMMA) substrate functions as a superhydrophilic
      membrane similar to paper. We first estimated the flow rate for pure water on
      microgrooves fabricated at various laser fluences in the range from 9.2 to 100.8
      J/cm2. The results showed that the flow rate could be tuned in the range from
      0.30 to 12.07 MUL/s by varying the laser irradiation parameters. The fluid flow
      was reproducible, with a calculated relative standard deviation (RSD%) of less
      than 8% in the flow rate. We then fabricated a microfilter for blood separation
      and estimated its filtration ability using artificial blood containing resin
      microparticles. This method would be useful in a technology related to a paper
      based diagnostic device for precise reagent manipulation.

PMID- 29321455
TI  - Characteristics of Microfluidic Paper-based Analytical Devices Fabricated by Four
      Different Methods.
AB  - We report on the effects of fabrication methods, photolithography, wax printing,
      screen printing, and craft cutting, on selected properties of microfluidic paper
      based analytical devices (MUPADs): cost, fabrication precision, wicking rate, and
      analytical accuracy. Photolithography requires numerous fabrication steps, and an
      oxygen plasma treatment is necessary when using an aqueous solution. Although the
      boundary between the hydrophobic and hydrophilic areas in the MUPAD is sharpest,
      the obtained K-scale intensity in measuring of protein concentrations is lower
      than those of the devices by other methods. Wax printing offers the simplest and
      fastest fabrication, although solution leakage measures should be taken to
      improve the wicking rate and to prevent cross-contamination. Screen printing also
      offers easy fabrication. The screen-printed MUPAD has a good wicking performance
      and shows a high detection intensity. Craft cutting allows automated fabrication
      of many MUPADs at once. The craft cut MUPAD has the fastest wicking rate among
      the four MUPADs due to bare cellulose fibers. We consider that the detection
      intensity of this MUPAD can be raised by optimizing the evaporation rate.

PMID- 29321457
TI  - "Paper-based Analytical Devices".

PMID- 29321456
TI  - Detection and Quantification of Polyquaterniums via Polyion-Sensitive Ion
      Selective Optodes Inkjet Printed on Cellulose Paper.
AB  - A universal method for the detection, quantification, and characterization of
      polyquaterniums (PQs) in a simple background electrolyte solution and in more
      complex recreational swimming pool water samples is presented. This method
      involves the application of polycation-sensitive ion-selective optodes (ISOs)
      prepared by inkjet printing dinonylnaphthalenesulfonic acid (H+DNNS-) and
      chromoionophore I directly onto WhatmanTM qualitative filter paper. No
      plasticizer or added polymer matrix is required for the fabrication of the
      sensing layer which is coated on the cellulose fibers of the filter paper. PQ-6,
      PQ-2, PQ-10, and poly(2-methacryloxyethyltrimethylammonium) chloride (PMETAC) are
      used as model PQ species for direct optical detection at ppm levels. We further
      demonstrate that PQ-6 can be detected in recreational swimming pool water samples
      using this new type of sensor, and that detection of polyanions is also possible
      using an indirect detection method. Lastly, to circumvent the challenge of
      polyion-sensitive ISOs exhibiting a pH dependence, the sensors were soaked in
      buffer and dried to provide local buffering for applied liquid samples and an
      optical signal independent of sample pH.

PMID- 29321458
TI  - Wax-Assisted One-Step Enzyme-Linked Immunosorbent Assay on Lateral Flow Test
      Devices.
AB  - Lateral flow tests (LFTs) are widely used analytical tools characterized by
      portability, operator simplicity and short analysis times. A remaining challenge
      is their limited analytical sensitivity, which in classical immunoassay formats
      is overcome by enzyme-linked immunosorbent assay (ELISA) formats. The
      implementation of ELISA to an LFT format however, is hampered by the complexity
      of the procedure requiring the enzyme substrate addition after sample addition.
      In this work, a simple method for automation of this procedure without user
      interference is presented. Originally used sample pads of LFTs have been replaced
      by hydrophobic wax-modified filter paper-based sample pads to realize a delayed
      flow a pre-deposited colorimetric ELISA substrate without other alterations to
      the classical lateral-flow immunoassay format. The performance of the system has
      been characterized by visualizing flow behavior and final proof-of-concept is
      provided by a model mouse IgG assay, achieving a limit of detection of 15.8 ng mL
      1 from just a single application of the sample solution.

PMID- 29321460
TI  - Highly Sensitive Paper-based Analytical Devices with the Introduction of a Large
      Volume Sample via Continuous Flow.
AB  - The implementation of continuous flow in paper-based analytical devices (PADs)
      was challenging because of the large-volume introduction that was created; but
      this allowed for the development of novel types of PADs for preconcentration,
      separation, and sensitive detection. In this study, pump-free continuous flow was
      applied to a distance-based PAD for the determination of iron ions. Continuous
      flow enabled the introduction of a volume that exceeded what was necessary to
      fill the hydrophilic channel of a PAD. Thus, this continuous-flow method
      significantly improved both the limits of detection (LOD) and the limits of
      quantification (LOQ) for a distance-based PAD by increasing the sample volume
      that could be introduced into the PAD. The values for LOD and LOQ were 20 and 26
      ppb, respectively, which were more than 150-times lower than that obtained using
      a small sample volume (50 MUL), and were comparable to those of inductively
      coupled plasma-atomic emission spectrometry. The continuous-flow technique was
      applicable to the determination of iron ions at levels of several tens of ppb in
      natural water without preconcentration.

PMID- 29321459
TI  - Practical High-Performance Lateral Flow Assay Based on Autonomous Microfluidic
      Replacement on a Film.
AB  - Although paper-based microfluidic devices are an ideal platform for point-of-care
      (POC) diagnostics, it is difficult to achieve microfluidic control required for
      sensitive analyses such as ELISA on a paper substrate. Here, we present a novel
      lateral-flow test chip that can perform operations similar to a pump, such as
      flowing, stopping, and replacing a solution, just by adding the solution onto an
      inlet port. The chip was fabricated by laminating paper, film, and adhesive tape.
      For sensitive and accurate detection in an immunoassay, the transparency and
      flatness of the substrate is crucial for precise analysis of weak light generated
      by a specific antigen-antibody reaction; however, paper is not flat and is
      opaque. Therefore, transparent film was applied to the detection area of the chip
      in this study. The chip showed a good correlation at 0.1 - 100 ng ml-1
      concentrations of C-reactive protein, demonstrating high quantitative analysis of
      CRP in serum suitable for clinical trials. The signal intensity of the novel chip
      was higher than that of a chip made of nitrocellulose membrane, and the variation
      was smaller. The limit of detection of the chip was 0.1 ng ml-1, whereas that of
      the nitrocellulose membrane was 100 ng ml-1. This novel chip can be used for
      sensitive sandwich immunoassays just by adding solutions.

PMID- 29321461
TI  - Trends in Paper-based Electrochemical Biosensors: From Design to Application.
AB  - Electrochemical bio-sensing using paper-based detection systems is the main focus
      of this review. The different existing designs of 2-dimensional and 3-dimensional
      sensors, and fabrication techniques are discussed. This review highlights the
      effect of adopting different sensor designs, distinct fabrication techniques, as
      well as different modification methods, in order to produce reliable and
      reproducible reading. The use of various nanomaterials have been demonstrated in
      order to modify the surface of electrodes during fabrication to further enhance
      the signal for subsequent analysis. The reviewed sensors were classified into
      categories based on their applications, such as diagnostics, environmental and
      food testing. One of the major advantages of using paper-based electrochemical
      sensors is the potential for miniaturization, which only requires relatively
      small amount of samples, and the low cost for the purpose of mass production.
      Additionally, most of the devices reviewed were made to be portable, making them
      well-suited for on-site detection. Finally, paper-based detection is an ideal
      platform to fabricate cost-effective, user-friendly and sensitive electrochemical
      biosensors, with large capacity for customization depending on functional needs.

PMID- 29321462
TI  - Microfluidic Paper-based Analytical Device for the Determination of Hexavalent
      Chromium by Photolithographic Fabrication Using a Photomask Printed with 3D
      Printer.
AB  - This article describes a simple and inexpensive microfluidic paper-based
      analytical device (MUPAD) for the determination of hexavalent chromium (CrVI) in
      water samples. The MUPADs were fabricated on paper by photolithography using a
      photomask printed with a 3D printer and functionalized with reagents for a
      colorimetric assay. In the MUPAD, CrVI reacts with 1,5-diphenylcarbazide to form
      a violet-colored complex. Images of MUPADs were captured with a digital camera;
      then the red, green, and blue color intensity of each detection zone were
      measured using images processing software. The green intensity analysis was the
      best sensitive among the RGB color. A linear working range (40 - 400 ppm; R2 =
      0.981) between the CrVI and green intensity was obtained with a detection limit
      of 30 ppm. All of the recoveries were between 94 and 109% in recovery studies on
      water samples, and good results were obtained.

PMID- 29321463
TI  - Use of a Smartphone as a Colorimetric Analyzer in Paper-based Devices for
      Sensitive and Selective Determination of Mercury in Water Samples.
AB  - A smartphone application, called CAnal, was developed as a colorimetric analyzer
      in paper-based devices for sensitive and selective determination of mercury(II)
      in water samples. Measurement on the double layer of a microfluidic paper-based
      analytical device (MUPAD) fabricated by alkyl ketene dimer (AKD)-inkjet printing
      technique with special design doped with unmodified silver nanoparticles (AgNPs)
      onto the detection zones was performed by monitoring the gray intensity in the
      blue channel of AgNPs, which disintegrated when exposed to mercury(II) on MUPAD.
      Under the optimized conditions, the developed approach showed high sensitivity,
      low limit of detection (0.003 mg L-1, 3SD blank/slope of the calibration curve),
      small sample volume uptake (two times of 2 MUL), and short analysis time. The
      linearity range of this technique ranged from 0.01 to 10 mg L-1 (r2 = 0.993).
      Furthermore, practical analysis of various water samples was also demonstrated to
      have acceptable performance that was in agreement with the data from cold vapor
      atomic absorption spectrophotometry (CV-AAS), a conventional method. The proposed
      technique allows for a rapid, simple (instant report of the final mercury(II)
      concentration in water samples via smartphone display), sensitive, selective, and
      on-site analysis with high sample throughput (48 samples h-1, n = 3) of trace
      mercury(II) in water samples, which is suitable for end users who are unskilled
      in analyzing mercury(II) in water samples.

PMID- 29321464
TI  - Microfluidic Paper-based Analytical Device for Quantification of Lead Using
      Reaction Band-length for Identification of Bullet Hole and Its Potential for
      Estimating Firing Distance.
AB  - A low-cost and user-friendly microfluidic paper-based analytical device (MUPAD)
      was developed for identification of bullet hole from gunshot residue (GSR) on
      cotton fabric target. The device (25 * 82 mm) is made of filter paper with a
      printed pattern consisting of a circular sample loading reservoir (6 mm i.d.), a
      circular waste reservoir (4 mm i.d.) and a straight flow channel (3 mm wide and
      60 mm long). A sticker with a ruler scale in millimeters was mounted alongside
      the channel. The straight channel is first impregnated with rhodizonate and dried
      at ambient temperature. Tartrate extract of the target fabric is loaded on the
      sample reservoir. If Pb(II) ions are present in the extract, pink streak of
      Pb(II)-rhodizonate precipitate is formed as the sample solution flows from the
      reservoir along the channel. The length of the pink strip is employed to estimate
      the firing distance.

PMID- 29321465
TI  - Determination of Ascorbic Acid in Commercial Tablets Using Pencil Drawn
      Electrochemical Paper-based Analytical Devices.
AB  - This study describes the use of electrochemical paper-based analytical devices
      (ePADs) drawn with graphite pencil for the determination of ascorbic acid (AA) in
      commercial tablets. ePADs were fabricated using vegetal paper and graphite
      pencil. First, the three-electrode electrochemical cell drawn using a graphical
      software and toner lines were laser printed on the vegetal paper surface to
      delimit the electrode areas. Then, the electrode regions were manually painted
      with graphite pencil. Afterwards, the pseudo-reference electrode was defined with
      the deposition of silver ink over the graphite surface. Cyclic voltammetry and
      square wave voltammetry (SWV) experiments were performed to optimize the
      electroanalytical parameters as well as to quantitatively determine the AA
      concentration in two commercial tables. ePADs exhibited linear behavior for a
      concentration range between 0.5 and 3.0 mmol L-1. The achieved limit of detection
      and sensitivity were 70 MUmol L-1 and 0.47 MUA/mmol L-1, respectively. The AA
      concentration levels found by SWV experiments in both CenevitTM and Energil CTM
      were 2.80 +/- 0.02 and 3.10 +/- 0.01 mmol L-1, respectively. The accuracy of the
      proposed devices was investigated through recovery experiments in three
      concentration levels and it presented values between 95 and 115%.

PMID- 29321466
TI  - An Instrument-free Detection of Antioxidant Activity Using Paper-based Analytical
      Devices Coated with Nanoceria.
AB  - This work reports a portable distance-based detection paper device that has a
      thermometer-like shape for rapid, instrument-free determination of antioxidant
      activity using a nanoceria assay. The assay is based on partial reduction of
      cerium ion from Ce4+ to Ce3+ on nanoceria deposited along the detection channel
      by antioxidants present in food, giving highly reactive oxidation products.
      Either these products or the parent antioxidant compounds could then bind to the
      OH-rich ceria nanoparticles and generate charge transfer ceria-antioxidant
      complexes resulting in a yellow to brown color change. The distance of the brown
      color on the detection channel is directly proportional to antioxidant activity,
      and can be easily measured using an integrated ruler without the need of any
      external sophisticated instrument for detection. The paper sensor has been
      studied for the analysis of common antioxidants and its performance was validated
      against traditional antioxidant assays for 11 tea sample analyses. Using the
      Spearman rank correlation coefficient method, the antioxidant activity of tea
      samples obtained from the paper device correlated with the traditional assay at
      the 95% confidence level. The developed sensor provided a high recovery and
      tolerance limit and was stable for 50 days both when stored at ambient and low
      temperature (6 and -20 degrees C). The results demonstrated that the developed
      paper device is an alternative to allow for fast, simple, instrument-free, cheap,
      portable and high-throughput screening of antioxidant activity analysis in real
      samples.

PMID- 29321469
TI  - Publisher Correction: Superplasticity in a lean Fe-Mn-Al steel.
AB  - The original PDF version of this Article omitted to state that "Jeongho Han and
      Seok-Hyeon Kang contributed equally to this work" in the affiliations section.
      This has now been corrected in the PDF version of the Article. The HTML version
      was correct from the time of publication.

PMID- 29321467
TI  - Importance of Regular and Maintenance Therapy Adherence in Neuromyelitis Optica
      (NMO): Lessons from a Repeating Relapse Case.
AB  - BACKGROUND Neuromyelitis optica (NMO) is a rare demyelinating disease of the
      central nervous system; NMO predominantly affects the spinal cord and optic
      nerves. The diagnosis is based on history, clinical presentation, seropositive
      NMO-IgG antibody, and notably, exclusion of other diseases. Despite the absence
      of definitive therapeutic strategies for NMO, methylprednisolone pulse therapy
      and plasma exchange are used for acute phase treatment, while immunosuppressive
      agent(s) are recommended to prevent relapses and improve prognosis. Here, we
      report a repeating relapse NMO case due to lack of regular and maintenance
      therapy. CASE REPORT A 58-year-old female with chronic NMO presented with a three
      day history of new-onset right leg weakness and pain. The patient was diagnosed
      with NMO three years ago and presented with her fourth attacks. During her
      initial diagnosis, she was initiated on steroids. One year later, she developed
      the first relapse and was treated with steroids and rituximab, leading to 1.5
      year remission. After the second relapse, steroids and rituximab was still given
      as maintenance therapy, but was not followed. Thus, the third relapse occurred in
      five months. During this hospitalization, she received initially high-dose
      solumedrol (1 g daily for five days) in addition to gabapentin 100 mg (gradually
      increased to 300 mg) three times a day for muscle spasms. Due to worsening of
      paresthesia and hemiparesis, it was decided to place her on plasma exchange
      treatment. After two plasma exchanges, the patient's condition was improved and
      she regained strength in her lower extremity. She completed five more cycles of
      plasma exchange, and was then discharged on steroid therapy (prednisone 20 mg
      daily for 10 days then taper) as maintenance therapy and with follow-up in
      neurology clinic. CONCLUSIONS Over the span of three years, the patient has had
      three relapses since her NMO diagnosis where her symptoms have worsened. Steroid
      therapy alone seemed not insufficient in managing her more recent relapses.
      Nonadherence to NMO treatment likely increased her risk for recurrence, thus
      regular and long-term maintenance therapy is imperative to delay the progression
      and prevent relapse in NMO.

PMID- 29321468
TI  - Length of Stay and Functional Outcomes Among Patients with Stroke Discharged from
      an Inpatient Rehabilitation Facility in Saudi Arabia.
AB  - BACKGROUND In many countries, the length of stay (LOS) for inpatient
      rehabilitation following stroke has gradually decreased. It is unclear whether
      this trend is associated with differences in functional outcomes, especially in
      developing countries. This study aimed to examine associations between LOS and
      functional outcomes among patients with stroke discharged from an inpatient
      rehabilitation facility in Saudi Arabia. MATERIAL AND METHODS This retrospective
      study included all patients (N=409) aged >=18 years who were admitted to an
      inpatient rehabilitation for stroke during 2008-2014. There were no deaths in the
      cohort during the study period. Patients were divided into 4 groups according to
      days of rehabilitation: <=30 days (n=114), 31-60 days (n=199), 61-90 days (n=72),
      and >90 days (n=24). Multivariate regression analyses were used to evaluate
      functional outcomes using the functional independence measure (FIM). RESULTS The
      fully adjusted model showed that higher total and subscale FIM scores were
      significantly associated with a LOS <=30 days (total beta: 18.2, standard error
      [SE]=4.43, P<=0.0001; motor-FIM: beta=13.9, SE=3.70, P=0.0002; cognitive-FIM:
      beta=4.3, SE=1.29, P=0.001), and 31-60 days (total beta: 11.3, SE=4.07, P=0.005;
      motor-FIM: beta=8.8, SE=3.40, P=0.009; cognitive-FIM: beta=2.4, SE=1.19, P=0.038)
      compared with >90 days. CONCLUSIONS A short or intermediate LOS is not
      necessarily associated with worse outcomes, assuming adequate care is provided.

PMID- 29321470
TI  - Author Correction: Re-designing Interleukin-12 to enhance its safety and
      potential as an anti-tumor immunotherapeutic agent.
AB  - The originally published version of this Article contained errors in Figure 4. In
      panel b, the square and diamond labels associated with the uppermost survival
      curve were incorrectly displayed as 'n' and 'u', respectively. These errors have
      now been corrected in both the PDF and HTML versions of the Article.

PMID- 29321471
TI  - Author Correction: Signatures of the topological s+- superconducting order
      parameter in the type-II Weyl semimetal T d -MoTe2.
AB  - The original version of this article omitted the following from the
      Acknowledgements: "CAM and AL were supported by the NSF MRSEC program through
      Columbia in the Center for Precision Assembly of Superstratic and Superatomic
      Solids (DMR-1420634). Additionally, this research used resources of the National
      Energy Research Scientific Computing Center, a DOE Office of Science User
      Facility supported by the Office of Science of the U.S. Department of Energy
      under 'Contract No. DE-AC02-05CH11231'." This has now been corrected in both the
      PDF and HTML versions of the article.

PMID- 29321473
TI  - Ancient environmental DNA reveals shifts in dominant mutualisms during the late
      Quaternary.
AB  - DNA-based snapshots of ancient vegetation have shown that the composition of high
      latitude plant communities changed considerably during the late Quaternary.
      However, parallel changes in biotic interactions remain largely uninvestigated.
      Here we show how mutualisms involving plants and heterotrophic organisms varied
      during the last 50,000 years. During 50-25 ka BP, a cool period featuring stadial
      interstadial fluctuations, arbuscular mycorrhizal and non-N-fixing plants
      predominated. During 25-15 ka BP, a cold, dry interval, the representation of
      ectomycorrhizal, non-mycorrhizal and facultatively mycorrhizal plants increased,
      while that of N-fixing plants decreased further. From 15 ka BP, which marks the
      transition to and establishment of the Holocene interglaciation, representation
      of arbuscular mycorrhizal plants decreased further, while that of
      ectomycorrhizal, non-mycorrhizal, N-fixing and wind-pollinated plants increased.
      These changes in the mutualist trait structure of vegetation may reflect
      responses to historical environmental conditions that are without current
      analogue, or biogeographic processes, such as spatial decoupling of mutualist
      partners.

PMID- 29321472
TI  - Desumoylase SENP6 maintains osteochondroprogenitor homeostasis by suppressing the
      p53 pathway.
AB  - The development, growth, and renewal of skeletal tissues rely on the function of
      osteochondroprogenitors (OCPs). Protein sumoylation/desumoylation has emerged as
      a pivotal mechanism for stem cell/progenitor homeostasis, and excessive
      sumoylation has been associated with cell senescence and tissue aging, but its
      role in regulating OCP function is unclear. Here we show that postnatal loss of
      the desumoylase SUMO1/sentrin-specific peptidase 6 (SENP6) causes premature
      aging. OCP-specific SENP6 knockout mice exhibit smaller skeletons, with elevated
      apoptosis and cell senescence in OCPs and chondrocytes. In Senp6 -/- cells, the
      two most significantly elevated pathways are p53 signaling and senescence
      associated secreted phenotypes (SASP), and Trp53 loss partially rescues the
      skeletal and cellular phenotypes caused by Senp6 loss. Furthermore, SENP6
      interacts with, desumoylates, and stabilizes TRIM28, suppressing p53 activity.
      Our data reveals a crucial role of the SENP6-p53 axis in maintaining OCP
      homeostasis during skeletal development.

PMID- 29321474
TI  - Magnetisation process in the rare earth tetraborides, NdB4 and HoB4.
AB  - A field-induced magnetisation process in the frustrated antiferromagnets is often
      much richer compared to the materials without competing interactions. The applied
      field tends to stabilise unusual spin configurations which frequently results in
      the appearance of magnetisation plateaux. Here we report a study into the field
      induced magnetisation of the two frustrated rare earth tetraborides, HoB4 and
      NdB4. NdB4 shows a fractional magnetisation plateau occurring at M/M sat ~
      [Formula: see text] before saturating in a field of 33 kOe. On cooling down to
      0.5 K the temperature dependent susceptibility of NdB4 shows an unconventional
      transition where the system returns to the zero field antiferromagnetic state
      from a higher-temperature ferrimagnetic state. We are able to reconstruct the
      magnetic phase diagram of NdB4 from the magnetisation, susceptibility and
      resistivity measurements for both H [Formula: see text] c and H ? c. For HoB4,
      the most interesting behaviour is found at the lowest temperature of 0.5 K, where
      the field dependent magnetisation demonstrates a new fractional [Formula: see
      text]-magnetisation plateau. Further insight into the relations between the
      exchange interactions and single ion effects is gained through high-field
      magnetisation measurements in both HoB4 and NdB4.

PMID- 29321475
TI  - Intraskeletal histovariability, allometric growth patterns, and their functional
      implications in bird-like dinosaurs.
AB  - With their elongated forelimbs and variable aerial skills, paravian dinosaurs, a
      clade also comprising modern birds, are in the hotspot of vertebrate evolutionary
      research. Inferences on the early evolution of flight largely rely on bone and
      feather morphology, while osteohistological traits are usually studied to explore
      life-history characteristics. By sampling and comparing multiple homologous fore-
      and hind limb elements, we integrate for the first time qualitative and
      quantitative osteohistological approaches to get insight into the intraskeletal
      growth dynamics and their functional implications in five paravian dinosaur taxa,
      Anchiornis, Aurornis, Eosinopteryx, Serikornis, and Jeholornis. Our qualitative
      assessment implies a considerable diversity in allometric/isometric growth
      patterns among these paravians. Quantitative analyses show that neither taxa nor
      homologous elements have characteristic histology, and that ontogenetic stage,
      element size and the newly introduced relative element precocity only partially
      explain the diaphyseal histovariability. Still, Jeholornis, the only avialan
      studied here, is histologically distinct from all other specimens in the
      multivariate visualizations raising the hypothesis that its bone tissue
      characteristics may be related to its superior aerial capabilities compared to
      the non-avialan paravians. Our results warrant further research on the
      osteohistological correlates of flight and developmental strategies in birds and
      bird-like dinosaurs.

PMID- 29321477
TI  - Giant electrocaloric effect in a wide temperature range in PbTiO3 nanoparticle
      with double-vortex domain structure.
AB  - Electrocaloric effect (ECE) has the potential applications in solid-state
      refrigeration with the features of high efficiency and environmentally friendly.
      Large adiabatic temperature change in a wide temperature range is needed for
      electrocaloric effect to meet the requirement of commercially application. In
      this work, giant electrocaloric effect is found in PbTiO3 nanoparticle with
      double-vortex domain structure in a wide temperature range by using phase field
      method, which the lowest and highest adiabatic temperature change (DeltaT) is 7.2
      K and 16.5 K, respectively. The influence of misfit strain on the ECE of PbTiO3
      nanoparticle with the double-vortex domain structure is investigated, and results
      show that the compress misfit strain can enhance the ECE, but the tensile misfit
      strain reduces the ECE. This work reveals a way to obtain giant ECE of
      ferroelectric materials by domain engineering and strain engineering in a wide
      temperature range.

PMID- 29321476
TI  - Sample handling of gastric tissue and O-glycan alterations in paired gastric
      cancer and non-tumorigenic tissues.
AB  - Sample collection, handling and storage are the most critical steps for ensuring
      the highest preservation of specimens. Pre-analytical variability can influence
      the results as protein signatures alter rapidly after tissue excision or during
      long-term storage. Hence, we evaluated current state-of-the-art biobank
      preservation methods from a glycomics perspective and analyzed O-glycan
      alterations occurring in the gastric cancer tissues. Paired tumor and adjacent
      normal tissue samples were obtained from six patients undergoing gastric cancer
      surgery. Collected samples (n = 24) were either snap-frozen or heat stabilized
      and then homogenized. Glycans were released from extracted glycoproteins and
      analyzed by LC-MS/MS. In total, the relative abundance of 83 O-glycans and 17
      derived structural features were used for comparison. There was no statistically
      significant difference found in variables between snap frozen and heat-stabilized
      samples, which indicated the two preservation methods were comparable. The data
      also showed significant changes between normal and cancerous tissue. In addition
      to a shift from high sialylation in the cancer area towards blood group ABO in
      the normal area, we also detected that the LacdiNAc epitope (N,N'
      diacetyllactosamine) was significantly decreased in cancer samples. The O-glycan
      alterations that are presented here may provide predictive power for the
      detection and prognosis of gastric cancer.

PMID- 29321478
TI  - Reprogramming of pro-inflammatory human macrophages to an anti-inflammatory
      phenotype by bile acids.
AB  - Cholestasis is caused by autoimmune reactions, drug-induced hepatotoxicity, viral
      infections of the liver and the obstruction of bile ducts by tumours or
      gallstones. Cholestatic conditions are associated with impaired innate and
      adaptive immunity, including alterations of the cellular functions of monocytes,
      macrophages, NK cells and T-cells. Bile acids act as signalling molecules,
      affecting lipopolysaccharide (LPS)-induced cytokine expression in primary human
      macrophages. The present manuscript investigates the impact of bile acids, such
      as taurolithocholic acid (TLC), on the transcriptome of human macrophages in the
      presence or absence of LPS. While TLC itself has almost no effect on gene
      expression under control conditions, this compound modulates the expression of
      202 out of 865 transcripts in the presence of LPS. Interestingly, pathway
      analysis revealed that TLC specifically supressed the expression of genes
      involved in mediating pro-inflammatory effects, phagocytosis, interactions with
      pathogens and autophagy as well as the recruitment of immune cells, such as NK
      cells, neutrophils and T cells. These data indicate a broad influence of bile
      acids on inflammatory responses and immune functions in macrophages. These
      findings may contribute to the clinical observation that patients with
      cholestasis present a lack of response to bacterial or viral infections.

PMID- 29321479
TI  - Contrasting patterns of leaf trait variation among and within species during
      tropical dry forest succession in Costa Rica.
AB  - A coordinated response to environmental drivers amongst individual functional
      traits is central to the plant strategy concept. However, whether the trait co
      ordination observed at the global scale occurs at other ecological scales
      (especially within species) remains an open question. Here, for sapling
      communities of two tropical dry forest types in Costa Rica, we show large
      differences amongst traits in the relative contribution of species turnover and
      intraspecific variation to their directional changes in response to environmental
      changes along a successional gradient. We studied the response of functional
      traits associated with the leaf economics spectrum and drought tolerance using
      intensive sampling to analyse inter- and intra-specific responses to
      environmental changes and ontogeny. Although the overall functional composition
      of the sapling communities changed during succession more through species
      turnover than through intraspecific trait variation, their relative contributions
      differed greatly amongst traits. For instance, community mean specific leaf area
      changed mostly due to intraspecific variation. Traits of the leaf economics
      spectrum showed decoupled responses to environmental drivers and ontogeny. These
      findings emphasise how divergent ecological mechanisms combine to cause great
      differences in changes of individual functional traits over environmental
      gradients and ecological scales.

PMID- 29321481
TI  - Anomalous Hall-like effect probe of antiferromagnetic domain wall.
AB  - Of crucial importance to antiferromagnetic (AF) spintronic devices, AF domain
      wall (AFDW), created in exchange biased Y3Fe5O12/Ni0.50Co0.50O (NiCoO)/Pt, is
      characterized by anomalous Hall-like effect through magnetic proximity effect and
      spin Hall magnetoresistance at NiCoO/Pt interface. The AFDW thickness, in the
      order of nanometers, has been for the first time proved in experiments to
      increase with increasing temperature. AF spins within AFDW show the same
      chirality in decent and ascent branches of ferromagnetic magnetization reversal
      process. Moreover, the uncompensated magnetic moment at the NiCoO/Pt interface is
      of perpendicular magnetization anisotropy and changes linearly in magnitude with
      temperature due to the reduced coordination of the magnetic atoms on the AF
      surface. This work will help to clarify the mechanism of the spin current
      propagation in AF materials and fully understand the physics behind exchange
      bias.

PMID- 29321480
TI  - Domain swapping and SMYD1 interactions with the PWWP domain of human hepatoma
      derived growth factor.
AB  - The human hepatoma-derived growth factor (HDGF), containing the chromatin
      associated N-terminal PWWP domain capable of binding the SMYD1 promoter,
      participates in various cellular processes and is involved in human cancers. We
      report the first crystal structures of the human HDGF PWWP domain (residues 1
      100) in a complex with SMYD1 of 10 bp at 2.84 A resolution and its apo form at
      3.3 A, respectively. The structure of the apo PWWP domain comprises mainly four
      beta-strands and two alpha-helices. The PWWP domain undergoes domain swapping to
      dramatically transform its secondary structures, altering the overall
      conformation from monomeric globular folding into an extended dimeric structure
      upon DNA binding. The flexible loop2, as a hinge loop with the partially built
      structure in the apo PWWP domain, notably refolds into a visible and stable alpha
      helix in the DNA complex. The swapped PWWP domain interacts with the minor
      grooves of the DNA through residues Lys19, Gly22, Arg79 and Lys80 in varied ways
      on loops 1 and 4 of the two chains, and the structure becomes more rigid than the
      apo form. These novel structural findings, together with physiological and
      activity assays of HDGF and the PWWP domain, provide new insights into the DNA
      binding mechanism of HDGF during nucleosomal functions.

PMID- 29321482
TI  - Enhanced YAP expression leads to EGFR TKI resistance in lung adenocarcinomas.
AB  - Epidermal growth factor receptor (EGFR) mutation is prevalently expressed in lung
      adenocarcinoma cases and acts as one of the major driving oncogenes. EGFR
      tyrosine kinase inhibitors (TKIs) have been used in patients with EGFR-mutant as
      an effective targeted therapy in lung adenocarcinoma, but drug resistance and
      tumor recurrence inevitably occurs. Recently, Yes-associate protein (YAP) has
      been reported to promote multiple cancer cell properties, such as promoting cell
      proliferation, epithelial-mesenchymal transition and drug resistance. This study
      investigated the roles of YAP in TKI-resistant lung adenocarcinoma. In TKI
      sensitive cells, enhanced YAP expression leads to TKI resistant. Also,
      upregulated YAP expression and activation were detected in long-term TKI-induced
      resistant cells. With reduced YAP expression using shRNA or YAP inhibitors, TKI
      resistant cells become TKI-sensitive. reduced xenograft tumor size in nude mice
      and Moreover, combined EGFR TKI and a YAP inhibitor, statin, prolonged survival
      among lung cancer patients analyzed by Taiwan National Health Insurance Research
      database. These observations revealed the importance of YAP in promoting TKI
      resistance and combined YAP inhibition can be a potential therapy delaying the
      occurrence of TKI-resistance in lung adenocarcinoma.

PMID- 29321483
TI  - Extracellular Total Electrolyte Concentration Imaging for Electrical Brain
      Stimulation (EBS).
AB  - Techniques for electrical brain stimulation (EBS), in which weak electrical
      stimulation is applied to the brain, have been extensively studied in various
      therapeutic brain functional applications. The extracellular fluid in the brain
      is a complex electrolyte that is composed of different types of ions, such as
      sodium (Na+), potassium (K+), and calcium (Ca+). Abnormal levels of electrolytes
      can cause a variety of pathological disorders. In this paper, we present a novel
      technique to visualize the total electrolyte concentration in the extracellular
      compartment of biological tissues. The electrical conductivity of biological
      tissues can be expressed as a product of the concentration and the mobility of
      the ions. Magnetic resonance electrical impedance tomography (MREIT) investigates
      the electrical properties in a region of interest (ROI) at low frequencies (below
      1 kHz) by injecting currents into the brain region. Combining with diffusion
      tensor MRI (DT-MRI), we analyze the relation between the concentration of ions
      and the electrical properties extracted from the magnetic flux density
      measurements using the MREIT technique. By measuring the magnetic flux density
      induced by EBS, we propose a fast non-iterative technique to visualize the total
      extracellular electrolyte concentration (EEC), which is a fundamental component
      of the conductivity. The proposed technique directly recovers the total EEC
      distribution associated with the water transport mobility tensor.

PMID- 29321484
TI  - Loss of tolerance to gut immunity protein, glycoprotein 2 (GP2) is associated
      with progressive disease course in primary sclerosing cholangitis.
AB  - Glycoprotein 2[GP2] is a specific target of pancreatic autoantibodies[PAbs] in
      Crohn's disease(CD) and is involved in gut innate immunity processes. Our aim was
      to evaluate the prevalence and prognostic potential of PAbs in primary sclerosing
      cholangitis(PSC). Sixty-five PSC patients were tested for PAbs by indirect
      immunofluorescence and compared with healthy (n = 100) and chronic liver disease
      controls(CLD, n = 488). Additionally, a panel of anti-microbial antibodies and
      secretory (s)IgA levels were measured, as markers of bacterial translocation and
      immune dysregulation. PAbs were more frequent in PSC(46.2%) compared to
      controls(healthy:0% and CLD:4.5%), [P < 0.001, for each]. Occurrence of anti-GP2
      antibody was 30.8% (20/65) and was exclusively of IgA isotype. Anti-GP2 IgA
      positive patients had higher sIgA levels (P = 0.021). With flow-cytometry, 68.4%
      (13/19) of anti-GP2 IgA antibodies were bound with secretory component,
      suggesting an active retro-transportation of anti-GP2 from the gut lumen to the
      mucosa. Anti-GP2 IgA was associated with shorter transplant-free survival
      [PLogRank < 0.01] during the prospective follow-up (median, IQR: 87 [9-99]
      months) and remained an independent predictor after adjusting for Mayo risk
      score(HR: 4.69 [1.05-21.04], P = 0.043). These results highlight the significance
      of gut-liver interactions in PSC. Anti-GP2 IgA might be a valuable tool for risk
      stratification in PSC and considered as a potential therapeutic target.

PMID- 29321486
TI  - New insights on basivenal sclerites using 3D tools and homology of wing veins in
      Odonatoptera (Insecta).
AB  - Being implied in flight, mimetism, communication, and protection, the insect
      wings were crucial organs for the mega diversification of this clade. Despite
      several attempts, the problem of wing evolution remains unresolved because the
      basal parts of the veins essential for vein identification are hidden in the
      basivenal sclerites. The homologies between wing characters thus cannot be
      accurately verified, while they are of primary importance to solve long-standing
      problems, such as the monophyly of the Palaeoptera, viz. Odonatoptera,
      Panephemeroptera, and Palaeozoic Palaeodictyopterida mainly known by their wings.
      Hitherto the tools to homologize venation were suffering several cases of
      exceptions, rendering them unreliable. Here we reconstruct the odonatopteran
      venation using fossils and a new 3D imaging tool, resulting congruent with the
      concept of Riek and Kukalova-Peck, with important novelties, viz. median anterior
      vein fused to radius and radius posterior nearly as convex as radius anterior
      (putative synapomorphies of Odonatoptera); subcostal anterior (ScA) fused to
      costal vein and most basal primary antenodal crossvein being a modified posterior
      branch of ScA (putative synapomorphies of Palaeoptera). These findings may reveal
      critical for future analyses of the relationships between fossil and extant
      Palaeoptera, helping to solve the evolutionary history of the insects as a whole.

PMID- 29321485
TI  - Role of diffusion-weighted imaging in the discrimination of benign and metastatic
      parotid area lymph nodes in patients with nasopharyngeal carcinoma.
AB  - To assess the utility of apparent diffusion coefficient (ADC) determined on
      diffusion-weighted MR imaging (DWI) to differentiate between benign and malignant
      parotid area lymph nodes (PLN) in nasopharyngeal carcinoma (NPC) patients. Thirty
      nine consecutive NPC patients with a total of 40 enlarged, biopsied PLNs
      underwent DWI examination. ADC values for benign and malignant PLNs were measured
      and compared. Receiver operating characteristic (ROC) curve analysis was to
      evaluate the optimal threshold level of ADC values for metastatic PLNs. The kappa
      was to assess the degree of agreement between histopathological diagnoses and ADC
      values, or imaging features of PLNs on MRI. We found the mean ADC value for
      benign PLNs was markedly higher than malignant PLNs. A threshold ADC of 1.01 * 10
      3 mm2/s was associated with a sensitivity of 85.7% and a specificity of 72.7%
      (area under the curve: 0.84). A moderate agreement was observed between the
      histopathological diagnosis and the threshold of ADC value (k value: 0.483).
      However, short axis diameter, necrosis, extranodal extension, and regional
      grouping of PLNs on MRI showed only a fair agreement with the histopathological
      diagnosis (k value: 0.257, 0.305, 0.276, and 0.205, respectively). Therefore, DWI
      may be a promising technique to differentiate metastatic from benign PLNs.

PMID- 29321487
TI  - Rare Earth Elements Removal from Water Using Natural Polymers.
AB  - Adsorption of rare earth metals, Eu (III) and Nd (III) was investigated on a new
      environmental friendly material, thiourea functionalized cellulose. Before usage,
      the synthesized material was characterized by Fourrier Transform Infrared
      spectroscopy and energy dispersive X-ray analysis. The influence of adsorption
      parameters (adsorbent dosage, time, temperature and initial metal concentration)
      on adsorption capacity was investigated. Experimental data were fitted by using
      the pseudo-first-order and pseudo-second-order kinetic models. Simultaneously
      thermodynamic and equilibrium studies have been carried out using Langmuir,
      Freundlich and Sips isotherm. Maximum adsorption capacities were reached in 30
      minutes at 298 K having the value of 27 mg/g for Eu (III) and 73 mg/g for Nd
      (III).

PMID- 29321488
TI  - Bt cotton producing Cry1Ac and Cry2Ab does not harm two parasitoids, Cotesia
      marginiventris and Copidosoma floridanum.
AB  - Cabbage looper, Trichoplusia ni (Hubner) is an important lepidopteran pest on
      many vegetable and greenhouse crops, and some field crops. Although there are no
      commercial transgenic Bt vegetable or greenhouse crops, T. ni is a target of
      Bollgard II cotton, which produces Cry1Ac and Cry2Ab. We expand on previous work
      that examined the effect of Bt crops on parasitoids using Bt-resistant
      lepidopteran populations as hosts. Cry1Ac/Cry2Ab-resistant T. ni larvae were used
      to eliminate host quality effects and to evaluate the direct effects of Bt cotton
      on the parasitoids Copidosoma floridanum (Ashmead) and Cotesia marginiventris
      (Cresson). These tri-trophic studies confirm that Bt cotton had no significant
      impact on development, success of parasitism, survival and adult longevity of C.
      marginiventris when using Bt-resistant T. ni fed on Bt cotton. Similarly, this Bt
      cotton had no significant impact on the development, mummy weight and the number
      of progeny produced by C. floridanum. Our studies verified that lyophilized Bt
      crop tissue maintained its insecticidal bioactivity when incorporated into an
      artificial diet, demonstrating that hosts and parasitoids were exposed to active
      Cry proteins. The egg-larval parasitoid C. floridanum, or similar species that
      consume their entire host, should be considered useful surrogates in risk
      assessment of Bt crops to non-target arthropods.

PMID- 29321489
TI  - Effects of slit width on water permeation through graphene membrane by molecular
      dynamics simulations.
AB  - Graphene membranes can be used for nanoscale filtration to remove atoms and are
      expected to be used for separation. To realize high-permeability and high
      filtration performance, we must understand the flow configuration in the
      nanochannels. In this study, we investigated the applicability of continuum
      dynamics laws to water flow through a graphene slit. We calculated the
      permeability of the flow through a slit using classical molecular dynamics (MD)
      and compared the MD simulation results for different Knudsen numbers (Kn) to
      predictions based on the no-slip model and slip model. Consequently, the flow
      through the graphene nanoslit was treated as slip flow only in the range of Kn <
      0.375. This study provides guidelines for the development of graphene filtration
      membranes.

PMID- 29321490
TI  - The interaction between BSA and DOTAP at the air-buffer interface.
AB  - In this article, the interaction between bovine serum albumin (BSA) and the
      cationic 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) at the air-buffer
      interface was investigated at different subphase's pH values (pH = 3, 5 and 10).
      Surface pressure measurements (pi - A) and penetration kinetics process (pi - t)
      were carried out to reveal the interaction mechanism and the dynamical behavior.
      The data showed that pi - A isotherms moved towards larger mean molecular area
      when the concentration of BSA ([BSA]) increased, the amount of BSA adsorbed onto
      DOTAP monolayer reached a threshold value at a [BSA] of 5 * 10-8 M, and BSA
      desorbed from the lipid monolayer as time goes by. The results revealed that the
      association of BSA with DOTAP at the air-buffer interface was affected by the
      subphase's pH value. When pH = 10, the interaction mechanism between them was a
      combination of hydrophobic interaction and electrostatic attraction, so BSA
      molecules could be well separated and purified from complex mixtures. AFM images
      demonstrated that pH value and [BSA] could affect the morphology feature of DOTAP
      monolayer and the adsorption and desorption processes of BSA. So the study
      provides an important experimental basis and theoretical support for learning the
      interaction mechanism among biomolecules in separation and purification of
      biomolecules and biosensor.

PMID- 29321491
TI  - Selective 6H-SiC White Light Emission by Picosecond Laser Direct Writing.
AB  - Displaying a full or tuneable emission spectrum with highly efficient is
      significant for luminescent materials used in solid-state lighting. Silicon
      carbide (SiC) has potential for use in photoelectric devices that operate under
      extreme conditions. In this paper, we present a method to selectively modify the
      photoluminescence (PL) properties of SiC by ultrafast laser direct writing. Based
      on this method, visible white PL could be observed by the naked eye at room
      temperature under ultraviolet excitation. By increasing the laser power intensity
      from 40 to 80 MW/cm2, the PL of the irradiated samples increased and pure white
      sunlight-like emission with controlled colour temperature was realised. The
      optimised laser power intensity of 65 MW/cm2 achieved a desirable colour
      temperature similar to that of sunlight (x = 0.33, y = 0.33 and colour
      temperature of 5500 K) and suppressed blue emission. By direct laser irradiation
      along designed scanning path, a large-scale and arbitrary pattern white emission
      was fabricated. The origin of the white luminescence was a mixture of multiple
      luminescent transitions of oxygen-related centres that turned the Si-C system
      into silicon oxycarbide. This work sheds light on new luminescent materials and a
      preparation technique for next-generation lighting devices.

PMID- 29321492
TI  - Quantification of silver nanoparticle toxicity to algae in soil via
      photosynthetic and flow-cytometric analyses.
AB  - Soil algae, which have received attention for their use in a novel bioassay to
      evaluate soil toxicity, expand the range of terrestrial test species. However,
      there is no information regarding the toxicity of nanomaterials to soil algae.
      Thus, we evaluated the effects of silver nanoparticles (0-50 mg AgNPs/kg dry
      weight soil) on the soil alga Chlamydomonas reinhardtii after six days, and
      assessed changes in biomass, photosynthetic activity, cellular morphology,
      membrane permeability, esterase activity, and oxidative stress. The parameters
      measured were markedly affected by AgNP-induced stress at 50 mg AgNPs/kg dry
      weight soil, where soil algal biomass, three measures of photosynthetic activity
      (area, reaction center per absorption flux, and reaction center per trapped
      energy flux), and esterase activity decreased. AgNPs also induced increases in
      both cell size and membrane permeability at 50 mg AgNPs/kg dry weight soil. In
      addition to the increase in cell size observed via microscopy, a mucilaginous
      sheath formed as a protective barrier against AgNPs. Thus, the toxicity of AgNPs
      can be effectively quantified based on the physiological, biochemical, and
      morphological responses of soil algae, where quantifying the level of toxicity of
      AgNPs to soil algae could prove to be a useful method in terrestrial
      ecotoxicology.

PMID- 29321493
TI  - Noncontact and instant detection of phosphor temperature in phosphor-converted
      white LEDs.
AB  - Phosphor-converted white light-emitting diodes (pc-WLEDs) have become a major
      light source in general lighting. To stabilize the photometric characteristics of
      pc-WLEDs, much effort has been made to manage the heat dissipation of the LED
      dies. The thermal problems of the phosphor parts, a critical reliability concern
      for pc-WLEDs, have recently attracted academic interest. This study proposed a
      practical approach for measuring phosphor temperature in an operating pc-WLED
      using a noncontact, instant detection method to remotely monitor the emission
      spectrum. Conventionally, an infrared camera or thermocouples have been used to
      measure temperature. An IR camera requires good calibration on the emissivity and
      is usually blocked by the lens or other components covered on the phosphors.
      Moreover, a thermocouple requires time to reach the thermal equivalence between
      the detector and the sample under testing, and this approach is destructive when
      used for inner detection. Our approach has advantages over the conventional
      methods because it is noninvasive, noncontact, and instant, and inner detection.
      The approach is also independent of the peak wavelength of pumping lights, the
      concentration and thickness of phosphor, and correlated color temperatures.

PMID- 29321494
TI  - Transplantation of olfactory ensheathing cells on functional recovery and
      neuropathic pain after spinal cord injury; systematic review and meta-analysis.
AB  - There are considerable disagreements on the application of olfactory ensheathing
      cells (OEC) for spinal cord injury (SCI) rehabilitation. The present meta
      analysis was designed to investigate the efficacy of OEC transplantation on motor
      function recovery and neuropathic pain alleviation in SCI animal models.
      Accordingly, all related studies were identified and included. Two independent
      researchers assessed the quality of the articles and summarized them by
      calculating standardized mean differences (SMD). OEC transplantation was shown to
      significantly improve functional recovery (SMD = 1.36; 95% confidence interval:
      1.05-1.68; p < 0.001). The efficacy of this method was higher in thoracic
      injuries (SMD = 1.41; 95% confidence interval: 1.08-1.74; p < 0.001) and
      allogeneic transplants (SMD = 1.53; 95% confidence interval: 1.15-1.90; p <
      0.001). OEC transplantation had no considerable effects on the improvement of
      hyperalgesia (SMD = -0.095; 95% confidence interval: -0.42-0.23; p = 0.57) but
      when the analyses were limited to studies with follow-up >=8 weeks, it was
      associated with increased hyperalgesia (SMD = -0.66; 95% confidence interval: 
      1.28-0.04; p = 0.04). OEC transplantation did not affect SCI-induced allodynia
      (SMD = 0.54; 95% confidence interval: -0.80-1.87; p = 0.43). Our findings showed
      that OEC transplantation can significantly improve motor function post-SCI, but
      it has no effect on allodynia and might lead to relative aggravation of
      hyperalgesia.

PMID- 29321495
TI  - Tanshinone IIA sulfonate protects against cigarette smoke-induced COPD and down
      regulation of CFTR in mice.
AB  - Chronic obstructive pulmonary disease (COPD) is a chronic lung disease
      characterized by abnormal inflammation, persistent and progressive lung function
      decline. The anti-inflammatory actions of tanshinone IIA, which is the most
      important active component from Chinese herbal medicine Danshen, have been well
      studied. However, it remains unknown whether sodium tanshinone IIA sulfonate
      (STS) protects against the development of COPD. Here we found that STS inhalation
      (5 mg/kg, 30 min per session, twice a day) significantly attenuated lung function
      decline, airspace enlargement, mucus production, bronchial collagen deposition,
      inflammatory responses and oxidative stress caused by cigarette smoke (CS) and
      lipopolysaccharide (LPS) exposures in mice. Moreover, treatment with STS (10
      MUg/ml) reduced CS extract (CSE)-induced IL-6 and IL-8 secretion in human
      bronchial epithelial (16HBE) cells. The anti-inflammatory actions of STS were
      associated with inhibition of ERK1/2 and NF-kappaB activations. Interestingly,
      STS inhibited CS-induced reduction of cystic fibrosis transmembrane conductance
      regulator (CFTR) in mouse lungs and in 16HBE cells. Treatment with a specific
      CFTR inhibitor CFTR-Inh172 augmented CSE-induced ERK1/2 and NF-kappaB-dependent
      inflammatory responses, but abolished the inhibitory action of STS on IL-6 and IL
      8 secretion in 16HBE cells. These results demonstrate that CS-induced COPD and
      down-regulation of CFTR are prevented by STS.

PMID- 29321496
TI  - Genistein promotes ionizing radiation-induced cell death by reducing cytoplasmic
      Bcl-xL levels in non-small cell lung cancer.
AB  - Genistein (GEN) has been previously reported to enhance the radiosensitivity of
      cancer cells; however, the detailed mechanisms remain unclear. Here, we report
      that GEN treatment inhibits the cytoplasmic distribution of Bcl-xL and increases
      nuclear Bcl-xL in non-small cell lung cancer (NSCLC). Interestingly, our in vitro
      data show that ionizing radiation IR treatment significantly increases IR-induced
      DNA damage and apoptosis in a low cytoplasmic Bcl-xL NSCLC cell line compared to
      that of high cytoplasmic Bcl-xL cell lines. In addition, clinical data also show
      that the level of cytoplasmic Bcl-xL was negatively associated with
      radiosensitivity in NSCLC. Furthermore, we demonstrated that GEN treatment
      enhanced the radiosensitivity of NSCLC cells partially due to increases in Beclin
      1-mediated autophagy by promoting the dissociation of Bcl-xL and Beclin-1. Taken
      together, these findings suggest that GEN can significantly enhance
      radiosensitivity by increasing apoptosis and autophagy due to inhibition of
      cytoplasmic Bcl-xL distribution and the interaction of Bcl-xL and Beclin-1 in
      NSCLC cells, respectively.

PMID- 29321497
TI  - Formation of Two-dimensional Electron Gas at Amorphous/Crystalline Oxide
      Interfaces.
AB  - Experimentally, we found the percentage of low valence cations, the ionization
      energy of cations in film, and the band gap of substrates to be decisive for the
      formation of two-dimensional electron gas at the interface of
      amorphous/crystalline oxide (a-2DEG). Considering these findings, we inferred
      that the charge transfer from the film to the interface should be the main
      mechanism of a-2DEG formation. This charge transfer is induced by oxygen defects
      in film and can be eliminated by the electron-absorbing process of cations in the
      film. Based on this, we propose a simple dipole model that successfully explains
      the origin of a-2DEG, our experimental findings, and some important properties of
      a-2DEG.

PMID- 29321499
TI  - May measurement month 2017-a concerted global effort to raise awareness of
      elevated blood pressure.

PMID- 29321498
TI  - The PPI network analysis of mRNA expression profile of uterus from primary
      dysmenorrheal rats.
AB  - To elucidate the mechanisms of molecular regulations underlying primary
      dysmenorrhea (PD), we used our previously published mRNA expression profile of
      uterus from PD syndrome rats to construct protein-protein interactions (PPI)
      network via STRING Interactome. Consequently, 34 subnetworks, including a
      "continent" (Subnetwork 1) and 33 "islands" (Subnetwork 2-34) were generated. The
      nodes, with relative expression ratios, were visualized in the PPI networks and
      their connections were identified. Through path and module exploring in the
      network, the bridges were found from pathways of cellular response to calcium
      ion, SMAD protein signal transduction, regulation of transcription from RNA
      polymerase II promoter in response to stress and muscle stretch that were
      significantly enriched by the up-regulated mRNAs, to the cascades of cAMP
      metabolic processes and positive regulation of cyclase activities by the down
      regulated ones. This link is mainly dependent on Fos/Jun - Vip connection. Our
      data, for the first time, report the PPI network analysis of differentially
      expressed mRNAs in the uterus of PD syndrome rats, to give insight into screening
      drugs and find new therapeutic strategies to relieve PD.

PMID- 29321500
TI  - On-Chip Fluorescence Switching System for Constructing a Rewritable Random Access
      Data Storage Device.
AB  - We report the development of on-chip fluorescence switching system based on DNA
      strand displacement and DNA hybridization for the construction of a rewritable
      and randomly accessible data storage device. In this study, the feasibility and
      potential effectiveness of our proposed system was evaluated with a series of wet
      experiments involving 40 bits (5 bytes) of data encoding a 5-charactered text
      (KRIBB). Also, a flexible data rewriting function was achieved by converting
      fluorescence signals between "ON" and "OFF" through DNA strand displacement and
      hybridization events. In addition, the proposed system was successfully validated
      on a microfluidic chip which could further facilitate the encoding and decoding
      process of data. To the best of our knowledge, this is the first report on the
      use of DNA hybridization and DNA strand displacement in the field of data storage
      devices. Taken together, our results demonstrated that DNA-based fluorescence
      switching could be applicable to construct a rewritable and randomly accessible
      data storage device through controllable DNA manipulations.

PMID- 29321501
TI  - Green synthesis of graphene oxide by seconds timescale water electrolytic
      oxidation.
AB  - Graphene oxide is highly desired for printing electronics, catalysis, energy
      storage, separation membranes, biomedicine, and composites. However, the present
      synthesis methods depend on the reactions of graphite with mixed strong oxidants,
      which suffer from explosion risk, serious environmental pollution, and long
      reaction time up to hundreds of hours. Here, we report a scalable, safe and green
      method to synthesize graphene oxide with a high yield based on water electrolytic
      oxidation of graphite. The graphite lattice is fully oxidized within a few
      seconds in our electrochemical oxidation reaction, and the graphene oxide
      obtained is similar to those achieved by the present methods. We also discuss the
      synthesis mechanism and demonstrate continuous and controlled synthesis of
      graphene oxide and its use for transparent conductive films, strong papers, and
      ultra-light elastic aerogels.

PMID- 29321502
TI  - The peroxisomal AAA-ATPase Pex1/Pex6 unfolds substrates by processive threading.
AB  - Pex1 and Pex6 form a heterohexameric motor essential for peroxisome biogenesis
      and function, and mutations in these AAA-ATPases cause most peroxisome-biogenesis
      disorders in humans. The tail-anchored protein Pex15 recruits Pex1/Pex6 to the
      peroxisomal membrane, where it performs an unknown function required for matrix
      protein import. Here we determine that Pex1/Pex6 from S. cerevisiae is a protein
      translocase that unfolds Pex15 in a pore-loop-dependent and ATP-hydrolysis
      dependent manner. Our structural studies of Pex15 in isolation and in complex
      with Pex1/Pex6 illustrate that Pex15 binds the N-terminal domains of Pex6, before
      its C-terminal disordered region engages with the pore loops of the motor, which
      then processively threads Pex15 through the central pore. Furthermore, Pex15
      directly binds the cargo receptor Pex5, linking Pex1/Pex6 to other components of
      the peroxisomal import machinery. Our results thus support a role of Pex1/Pex6 in
      mechanical unfolding of peroxins or their extraction from the peroxisomal
      membrane during matrix-protein import.

PMID- 29321503
TI  - IL-34 and CSF-1 display an equivalent macrophage differentiation ability but a
      different polarization potential.
AB  - CSF-1 and IL-34 share the CSF-1 receptor and no differences have been reported in
      the signaling pathways triggered by both ligands in human monocytes. IL-34
      promotes the differentiation and survival of monocytes, macrophages and
      osteoclasts, as CSF-1 does. However, IL-34 binds other receptors, suggesting that
      differences exist in the effect of both cytokines. In the present study, we
      compared the differentiation and polarization abilities of human primary
      monocytes in response to CSF-1 or IL-34. CSF-1R engagement by one or the other
      ligands leads to AKT and caspase activation and autophagy induction through
      expression and activation of AMPK and ULK1. As no differences were detected on
      monocyte differentiation, we investigated the effect of CSF-1 and IL-34 on
      macrophage polarization into the M1 or M2 phenotype. We highlighted a striking
      increase in IL-10 and CCL17 secretion in M1 and M2 macrophages derived from IL-34
      stimulated monocytes, respectively, compared to CSF-1 stimulated monocytes.
      Variations in the secretome induced by CSF-1 or IL-34 may account for their
      different ability to polarize naive T cells into Th1 cells. In conclusion, our
      findings indicate that CSF-1 and IL-34 exhibit the same ability to induce human
      monocyte differentiation but may have a different ability to polarize
      macrophages.

PMID- 29321504
TI  - Structural ensemble-based docking simulation and biophysical studies discovered
      new inhibitors of Hsp90 N-terminal domain.
AB  - Heat shock protein 90 (Hsp90) is one of the most abundant cellular proteins and
      plays a substantial role in the folding of client proteins. The inhibition of
      Hsp90 has been regarded as an attractive therapeutic strategy for treating cancer
      because many oncogenic kinases are Hsp90 client proteins. In this study, we
      report new inhibitors that directly bind to N-terminal ATP-binding pocket of
      Hsp90. Optimized structure-based virtual screening predicted candidate molecules,
      which was followed by confirmation using biophysical and cell-based assays. Among
      the reported crystal structures, we chose the two structures that show the most
      favourable early enrichments of true-positives in the receiver operating
      characteristic curve. Four molecules showed significant changes in the signals of
      2D [1H, 15N] correlation NMR spectroscopy. Differential scanning calorimetry
      analysis supported the results indicating direct binding. Quantified dissociation
      constant values of the molecules, determined by a series of 2D NMR experiments,
      lie in the range of 0.1-33 MUM. Growth inhibition assay with breast and lung
      cancer cells confirmed the cellular activities of the molecules. Cheminformatics
      revealed that the molecules share limited chemical similarities with known
      inhibitors. Molecular dynamics simulations detailed the putative binding modes of
      the inhibitors.

PMID- 29321507
TI  - Multifunctional Device based on phosphor-piezoelectric PZT: lighting, speaking,
      and mechanical energy harvesting.
AB  - We demonstrated the tri-functional device based on all powder-processing methods
      by using ZnS powder as phosphor layer and piezoelectric material as dielectric
      layer. The fabricated device generated the electroluminescent (EL) light from
      phosphor and the sound from piezoelectric sheet under a supply of external
      electric power, and additionally harvested the reverse-piezoelectric energy to be
      converted into EL light. Under sinusoidal applied voltage, EL luminances were
      exponentially increased with a maximum luminous efficiency of 1.3 lm/W at 40 V
      and 1,000 Hz, and sound pressure levels (SPLs) were linearly increased. The EL
      luminances were linearly dependent on applied frequency while the SPLs showed the
      parabolic increase behavior below 1,000 Hz and then the flat response. The
      temperature dependence on EL luminances and SPLs was demonstrated; the former was
      drastically increased and the latter was slightly decreased with the increase of
      temperature. Finally, as an energy harvesting application, the piezoelectric
      induced electroluminescence effect was demonstrated by applying only mechanical
      pressure to the device without any external electric power.

PMID- 29321506
TI  - Interference of chemical defence and sexual communication can shape the evolution
      of chemical signals.
AB  - According to current evolutionary theory, insect pheromones can originate from
      extant precursor compounds being selected for information transfer. This is
      exemplified by females of the parasitoid wasp Leptopilina heterotoma whose
      defensive secretion consisting mainly of (-)-iridomyrmecin has evolved secondary
      functions as cue to avoid other females during host search and as female sex
      pheromone. To promote our understanding of pheromone evolution from defensive
      secretions we studied the chemical ecology of Leptopilina clavipes. We show here
      that L. clavipes also produces a defensive secretion that contains (-)
      iridomyrmecin as major component and that females use it to detect and avoid host
      patches occupied by other females. However, the female sex pheromone of L.
      clavipes consists solely of cuticular hydrocarbons (CHCs) and males did not
      respond to female CHCs if presented in combination with the defensive secretion
      containing (-)-iridomyrmecin. This is in contrast to other species of
      Leptopilina, in which the iridoid compounds have no inhibiting effect or even
      function as sex pheromone triggering courtship behaviour. This indicates that
      Leptopilina species differ in the cost-benefit ratio for males searching for
      females, which might explain the strong divergence in the composition of the sex
      pheromone in the genus.

PMID- 29321505
TI  - Highly selective and sensitive macrocycle-based dinuclear foldamer for
      fluorometric and colorimetric sensing of citrate in water.
AB  - The selective detection of citrate anions is essential for various biological
      functions in living systems. A quantitative assessment of citrate is required for
      the diagnosis of various diseases in the human body; however, it is extremely
      challenging to develop efficient fluorescence and color-detecting molecular
      probes for sensing citrate in water. Herein, we report a macrocycle-based
      dinuclear foldamer (1) assembled with eosin Y (EY) that has been studied for
      anion binding by fluorescence and colorimetric techniques in water at neutral pH.
      Results from the fluorescence titrations reveal that the 1.EY ensemble strongly
      binds citrate anions, showing remarkable selectivity over a wide range of
      inorganic and carboxylate anions. The addition of citrate anions to the 1.EY
      adduct led to a large fluorescence enhancement, displaying a detectable color
      change under both visible and UV light in water up to 2 MUmol. The
      biocompatibility of 1.EY as an intracellular carrier in a biological system was
      evaluated on primary human foreskin fibroblast (HF) cells, showing an excellent
      cell viability. The strong binding properties of the ensemble allow it to be used
      as a highly sensitive, detective probe for biologically relevant citrate anions
      in various applications.

PMID- 29321508
TI  - Thrombospondin-1 secreted by human umbilical cord blood-derived mesenchymal stem
      cells rescues neurons from synaptic dysfunction in Alzheimer's disease model.
AB  - Alzheimer's disease (AD) is an incurable neurodegenerative disease characterised
      clinically by learning and memory impairments. Amyloid beta (Abeta) peptide
      induced synaptic dysfunction is a pathological process associated with early
      stage AD. Here, we show that paracrine action of human umbilical cord blood
      derived-mesenchymal stem cells (hUCB-MSCs) protects the hippocampus from synaptic
      density loss in in vitro and in vivo AD models. To identify paracrine factors
      underlying this rescue effect, we analysed hUCB-MSCs' secretome co-cultured with
      Abeta42-treated mouse hippocampal neurons. Thrombospondin-1 (TSP-1), a protein
      secreted by hUCB-MSCs in in vitro and 5XFAD AD mouse models, was selected for
      study. Treatment with exogenous recombinant TSP-1 or co-cultures with hUCB-MSCs
      significantly increased expression of synaptic-density markers, such as
      synaptophysin (SYP) and post-synaptic density protein-95 (PSD-95) in Abeta42
      treated mouse hippocampal neurons. Knockdown of TSP-1 expression in hUCB-MSCs
      through small interfering RNA (siRNA) abolished the reversal of Abeta42-induced
      hippocampal synaptic-density loss. We demonstrate that the rescue effect of hUCB
      MSC-secreted TSP-1 was mediated by neuroligin-1 (NLGN1) or alpha2delta-1
      receptors. Interestingly, NLGN1 and alpha2delta-1 expression, which was reduced
      in Abeta42-treated hippocampal neurons, increased in co-cultures with hUCB-MSCs
      or exogenous TSP-1. Together, these findings suggest that hUCB-MSCs can attenuate
      Abeta42-induced synaptic dysfunction by regulating TSP-1 release, thus providing
      a potential alternative therapeutic option for early-stage AD.

PMID- 29321509
TI  - Novel haemodialysis (HD) treatment employing molecular hydrogen (H2)-enriched
      dialysis solution improves prognosis of chronic dialysis patients: A prospective
      observational study.
AB  - Recent studies have revealed unique biological characteristics of molecular
      hydrogen (H2) as an anti-inflammatory agent. We developed a novel haemodialysis
      (E-HD) system delivering an H2 (30-80 ppb)-enriched dialysis solution by water
      electrolysis, and conducted a non-randomized, non-blinded, prospective
      observational study exploring its clinical impact. Prevalent chronic HD patients
      were allocated to either the E-HD (n = 161) group or the conventional HD (C-HD: n
      = 148) group, and received the respective HD treatments during the study. The
      primary endpoint was a composite of all-cause mortality and development of non
      lethal cardio-cerebrovascular events (cardiac disease, apoplexy, and leg
      amputation due to peripheral artery disease). During the 3.28-year mean
      observation period, there were no differences in dialysis parameters between the
      two groups; however, post-dialysis hypertension was ameliorated with significant
      reductions in antihypertensive agents in the E-HD patients. There were 91 events
      (50 in the C-HD group and 41 in the E-HD group). Multivariate analysis of the Cox
      proportional hazards model revealed E-HD as an independent significant factor for
      the primary endpoint (hazard ratio 0.59; [95% confidence interval: 0.38-0.92])
      after adjusting for confounding factors (age, cardiovascular disease history,
      serum albumin, and C-reactive protein). HD applying an H2-dissolved HD solution
      could improve the prognosis of chronic HD patients.

PMID- 29321510
TI  - A model of human lung fibrogenesis for the assessment of anti-fibrotic strategies
      in idiopathic pulmonary fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease
      with limited therapeutic options. KCa3.1 ion channels play a critical role in
      TGFbeta1-dependent pro-fibrotic responses in human lung myofibroblasts. We aimed
      to develop a human lung parenchymal model of fibrogenesis and test the efficacy
      of the selective KCa3.1 blocker senicapoc. 2 mm3 pieces of human lung parenchyma
      were cultured for 7 days in DMEM +/- TGFbeta1 (10 ng/ml) and pro-fibrotic
      pathways examined by RT-PCR, immunohistochemistry and collagen secretion.
      Following 7 days of culture with TGFbeta1, 41 IPF- and fibrosis-associated genes
      were significantly upregulated. Immunohistochemical staining demonstrated
      increased expression of ECM proteins and fibroblast-specific protein after
      TGFbeta1-stimulation. Collagen secretion was significantly increased following
      TGFbeta1-stimulation. These pro-fibrotic responses were attenuated by senicapoc,
      but not by dexamethasone. This 7 day ex vivo model of human lung fibrogenesis
      recapitulates pro-fibrotic events evident in IPF and is sensitive to KCa3.1
      channel inhibition. By maintaining the complex cell-cell and cell-matrix
      interactions of human tissue, and removing cross-species heterogeneity, this
      model may better predict drug efficacy in clinical trials and accelerate drug
      development in IPF. KCa3.1 channels are a promising target for the treatment of
      IPF.

PMID- 29321511
TI  - Enhancing vestibular function in the elderly with imperceptible electrical
      stimulation.
AB  - Age-related loss of vestibular function can result in decrements in gaze
      stabilization and increased fall risk in the elderly. This study was designed to
      see if low levels of electrical stochastic noise applied transcutaneously to the
      vestibular system can improve a gaze stabilization reflex in young and elderly
      subject groups. Ocular counter-rolling (OCR) using a video-based technique was
      obtained in 16 subjects during low frequency passive roll tilts. Consistent with
      previous studies, there was a significant reduction in OCR gains in the elderly
      compared to the young group. Imperceptible stochastic noise significantly
      increased OCR in the elderly (Mean 23%, CI: 17-35%). Increases in OCR gain were
      greatest for those with lowest baseline gain and were negligible in those with
      normal gain. Since stimulation was effective at low levels undetectable to
      subjects, stochastic noise may provide a new treatment alternative to enhance
      vestibular function, specifically otolith-ocular reflexes, in the elderly or
      patient populations with reduced otolith-ocular function.

PMID- 29321512
TI  - Phenotypic responses to interspecies competition and commensalism in a naturally
      derived microbial co-culture.
AB  - The fundamental question of whether different microbial species will co-exist or
      compete in a given environment depends on context, composition and environmental
      constraints. Model microbial systems can yield some general principles related to
      this question. In this study we employed a naturally occurring co-culture
      composed of heterotrophic bacteria, Halomonas sp. HL-48 and Marinobacter sp. HL
      58, to ask two fundamental scientific questions: 1) how do the phenotypes of two
      naturally co-existing species respond to partnership as compared to axenic
      growth? and 2) how do growth and molecular phenotypes of these species change
      with respect to competitive and commensal interactions? We hypothesized - and
      confirmed - that co-cultivation under glucose as the sole carbon source would
      result in competitive interactions. Similarly, when glucose was swapped with
      xylose, the interactions became commensal because Marinobacter HL-58 was
      supported by metabolites derived from Halomonas HL-48. Each species responded to
      partnership by changing both its growth and molecular phenotype as assayed via
      batch growth kinetics and global transcriptomics. These phenotypic responses
      depended on nutrient availability and so the environment ultimately controlled
      how they responded to each other. This simplified model community revealed that
      microbial interactions are context-specific and different environmental
      conditions dictate how interspecies partnerships will unfold.

PMID- 29321513
TI  - Tousled-like kinase 1 is a negative regulator of core transcription factors in
      murine embryonic stem cells.
AB  - Although the differentiation of pluripotent cells in embryonic stem cells (ESCs)
      is often associated with protein kinase-mediated signaling pathways and Tousled
      like kinase 1 (Tlk1) is required for development in several species, the role of
      Tlk1 in ESC function remains unclear. Here, we used mouse ESCs to study the
      function of Tlk1 in pluripotent cells. The knockdown (KD)-based Tlk1-deficient
      cells showed that Tlk1 is not essential for ESC self-renewal in an
      undifferentiated state. However, Tlk1-KD cells formed irregularly shaped embryoid
      bodies and induced resistance to differentiation cues, indicating their failure
      to differentiate into an embryoid body. Consistent with their failure to
      differentiate, Tlk1-KD cells failed to downregulate the expression of
      undifferentiated cell markers including Oct4, Nanog, and Sox2 during
      differentiation, suggesting a negative role of Tlk1. Interestingly, Tlk1
      overexpression sufficiently downregulated the expression of core pluripotency
      factors possibly irrespective of its kinase activity, thereby leading to a
      partial loss of self-renewal ability even in an undifferentiated state. Moreover,
      Tlk1 overexpression caused severe growth defects and G2/M phase arrest as well as
      apoptosis. Collectively, our data suggest that Tlk1 negatively regulates the
      expression of pluripotency factors, thereby contributing to the scheduled
      differentiation of mouse ESCs.

PMID- 29321515
TI  - Nationwide survey on cerebrotendinous xanthomatosis in Japan.
AB  - Cerebrotendinous xanthomatosis (CTX) is likely to be underdiagnosed and precise
      epidemiological characteristics of CTX are largely unknown as knowledge on the
      disorder is based mainly on case reports. We conducted a nationwide survey on CTX
      to elucidate the frequency, clinical picture, and molecular biological background
      of Japanese CTX patients. In this first Japanese nationwide survey on CTX, 2541
      questionnaires were sent to clinical departments across Japan. A total of 1032
      (40.6%) responses were returned completed for further analysis. Forty patients
      with CTX (50.0% male) were identified between September 2012 and August 2015. The
      mean age of onset was 24.5 +/- 13.6 years, mean age at diagnosis was 41.0 +/-
      11.6 years, and corresponding mean duration of illness from onset to diagnosis
      was 16.5 +/- 13.5 years. The most common initial symptom was tendon xanthoma,
      followed next by spastic paraplegia, cognitive dysfunction, cataract, ataxia, and
      epilepsy. The most predominant mutations in the CYP27A1 gene were c.1214G> A
      (p.R405Q, 31.6%), c.1421G> A (p.R474Q, 26.3%), and c.435G> T (p.G145=, 15.8%).
      Therapeutic interventions that included chenodeoxycholic acid, HMG-CoA reductase
      inhibitor, and LDL apheresis reduced serum cholestanol level in all patients and
      improved clinical symptoms in 40.5% of patients. Although CTX is a treatable
      neurodegenerative disorder, our nationwide survey revealed an average 16.5-year
      diagnostic delay. CTX may be underdiagnosed in Japan, especially during
      childhood. Early diagnosis and treatment are essential to improve the prognosis
      of CTX.

PMID- 29321514
TI  - Flavin Reductase Contributes to Pneumococcal Virulence by Protecting from
      Oxidative Stress and Mediating Adhesion and Elicits Protection Against
      Pneumococcal Challenge.
AB  - Pneumococcal flavin reductase (FlaR) is known to be cell-wall associated and
      possess age dependent antigenicity in children. This study aimed at
      characterizing FlaR and elucidating its involvement in pneumococcal physiology
      and virulence. Bioinformatic analysis of FlaR sequence identified three-conserved
      cysteine residues, suggesting a transition metal-binding capacity. Recombinant
      FlaR (rFlaR) bound Fe2+ and exhibited FAD-dependent NADP-reductase activity,
      which increased in the presence of cysteine or excess Fe2+ and inhibited by
      divalent-chelating agents. flaR mutant was highly susceptible to H2O2 compared to
      its wild type (WT) and complemented strains, suggesting a role for FlaR in
      pneumococcal oxidative stress resistance. Additionally, flaR mutant demonstrated
      significantly decreased mice mortality following intraperitoneal infection.
      Interestingly, lack of FlaR did not affect the extent of phagocytosis by primary
      mouse peritoneal macrophages but reduced adhesion to A549 cells compared to the
      WT and complemented strains. Noteworthy are the findings that immunization with
      rFlaR elicited protection in mice against intraperitoneal lethal challenge and
      anti-FlaR antisera neutralized bacterial virulence. Taken together, FlaR's roles
      in pneumococcal physiology and virulence, combined with its lack of significant
      homology to human proteins, point towards rFlaR as a vaccine candidate.

PMID- 29321516
TI  - Clinical and mutational spectrum of Japanese patients with recessive variants in
      SH3TC2.
AB  - SH3TC2, known as the causative gene of autosomal recessive demyelinating Charcot
      Marie-Tooth type 4C (CMT4C), was also found linked to a mild mononeuropathy of
      the median nerve with an autosomal dominant inheritance pattern. Using DNA
      microarray, Illumina MiSeq, and Ion proton, we carried out gene panel sequencing
      among 1483 Japanese CMT patients, containing 397 patients with demyelinating CMT.
      From seven patients with demyelinating CMT, we identified eight recessive
      variants in the SH3TC2 gene, consisting of five novel (pathogenic/likely
      pathogenic) and three reported variants. Additionally, from two patients with
      axonal CMT, we detected a reported recessive variant, p.Arg77Trp, which was
      herein reclassified as variant with unknown significance. Of the seven CMT4C
      patients (six females and one male), 2/7 patients developed symptoms at their
      first decade, and 5/7 patients lost their ambulation around age 50. Scoliosis was
      observed from more than half (4/7) of these patients, whereas hearing loss is the
      most common symptom of central nervous system (6/7). No median nerve
      mononeuropathy was recorded from their family members. We identified recessive
      variants in SH3TC2 from 1.76% of demyelinating CMT patients. An uncommon gender
      difference was recognized and the wild spectrum of these variants suggests
      mutational diversity of SH3TC2 in Japan.

PMID- 29321517
TI  - Genome-wide association study of homocysteine in African Americans from the
      Jackson Heart Study, the Multi-Ethnic Study of Atherosclerosis, and the Coronary
      Artery Risk in Young Adults study.
AB  - Homocysteine (Hcy) is a heritable biomarker for CVD, peripheral artery disease,
      stroke, and dementia. Little is known about genetic associations with Hcy in
      individuals of African ancestry. We performed a genome-wide association study for
      Hcy in 4927 AAs from the Jackson Heart Study (JHS), the Multi-Ethnic Study of
      Atherosclerosis (MESA), and the Coronary Artery Risk in Young Adults (CARDIA)
      study. Analyses were stratified by sex and results were meta-analyzed within and
      across sex. In the sex-combined meta-analysis, we observed genome-wide
      significant evidence (p < 5.0 * 10-8) for the NOX4 locus (lead variant rs2289125,
      beta = -0.15, p = 5.3 * 1011). While the NOX4 locus was previously reported as
      associated with Hcy in European-American populations, rs2289125 remained genome
      wide significant when conditioned on the previously reported lead variants.
      Previously reported genome-wide significant associations at NOX4, MTR, CBS, and
      MMACHC were also nominally (p < 0.050) replicated in AAs. Associations at the
      CPS1 locus, previously reported in females only, also was replicated specifically
      in females in this analysis, supporting sex-specific effects for this locus.
      These results suggest that there may be a combination of cross-population and
      population-specific genetic effects, as well as differences in genetic effects
      between males and females, in the regulation of Hcy levels.

PMID- 29321518
TI  - Mediation analysis of alcohol consumption, DNA methylation, and epithelial
      ovarian cancer.
AB  - Epigenetic factors and consumption of alcohol, which suppresses DNA methylation,
      may influence the development and progression of epithelial ovarian cancer (EOC).
      However, there is a lack of understanding whether these factors interact to
      affect the EOC risk. In this study, we aimed to gain insight into this
      relationship by identifying leukocyte-derived DNA methylation markers acting as
      potential mediators of alcohol-associated EOC. We implemented a causal inference
      test (CIT) and the VanderWeele and Vansteelandt multiple mediator model to
      examine CpG sites that mediate the association between alcohol consumption and
      EOC risk. We modified one step of the CIT by adopting a high-dimensional
      inference procedure. The data were based on 196 cases and 202 age-matched
      controls from the Mayo Clinic Ovarian Cancer Case-Control Study. Implementation
      of the CIT test revealed two CpG sites (cg09358725, cg11016563), which represent
      potential mediators of the relationship between alcohol consumption and EOC case
      control status. Implementation of the VanderWeele and Vansteelandt multiple
      mediator model further revealed that these two CpGs were the key mediators.
      Decreased methylation at both CpGs was more common in cases who drank alcohol at
      the time of enrollment vs. those who did not. cg11016563 resides in TRPC6 which
      has been previously shown to be overexpressed in EOC. These findings suggest two
      CpGs may serve as novel biomarkers for EOC susceptibility.

PMID- 29321519
TI  - Maturation of the gut microbiome and risk of asthma in childhood.
AB  - The composition of the human gut microbiome matures within the first years of
      life. It has been hypothesized that microbial compositions in this period can
      cause immune dysregulations and potentially cause asthma. Here we show, by
      associating gut microbial composition from 16S rRNA gene amplicon sequencing
      during the first year of life with subsequent risk of asthma in 690 participants,
      that 1-year-old children with an immature microbial composition have an increased
      risk of asthma at age 5 years. This association is only apparent among children
      born to asthmatic mothers, suggesting that lacking microbial stimulation during
      the first year of life can trigger their inherited asthma risk. Conversely,
      adequate maturation of the gut microbiome in this period may protect these pre
      disposed children.

PMID- 29321521
TI  - Coherence measure in terms of the Tsallis relative alpha entropy.
AB  - Coherence is the most fundamental quantum feature of the nonclassical systems.
      The understanding of coherence within the resource theory has been attracting
      increasing interest among which the quantification of coherence is an essential
      ingredient. A satisfactory measure should meet certain standard criteria. It
      seems that the most crucial criterion should be the strong monotonicity, that is,
      average coherence doesn't increase under the (sub-selective) incoherent
      operations. Recently, the Tsallis relative alpha entropy has been tried to
      quantify the coherence. But it was shown to violate the strong monotonicity, even
      though it can unambiguously distinguish the coherent and the incoherent states
      with the monotonicity. Here we establish a family of coherence quantifiers which
      are closely related to the Tsallis relative alpha entropy. It proves that this
      family of quantifiers satisfy all the standard criteria and particularly cover
      several typical coherence measures.

PMID- 29321520
TI  - Essential thrombocythemia treatment algorithm 2018.
AB  - Current drug therapy for myeloproliferative neoplasms, including essential
      thrombocythemia (ET) and polycythemia vera (PV), is neither curative nor has it
      been shown to prolong survival. Fortunately, prognosis in ET and PV is relatively
      good, with median survivals in younger patients estimated at 33 and 24 years,
      respectively. Therefore, when it comes to treatment in ET or PV, less is more and
      one should avoid exposing patients to new drugs that have not been shown to be
      disease-modifying, and whose long-term consequences are suspect (e.g.,
      ruxolitinib). Furthermore, the main indication for treatment in ET and PV is to
      prevent thrombosis and, in that regard, none of the newer drugs have been shown
      to be superior to the time-tested older drugs (e.g., hydroxyurea). We currently
      consider three major risk factors for thrombosis (history of thrombosis, JAK2/MPL
      mutations, and advanced age), in order to group ET patients into four risk
      categories: "very low risk" (absence of all three risk factors); "low risk"
      (presence of JAK2/MPL mutations); "intermediate-risk" (presence of advanced age);
      and "high-risk" (presence of thrombosis history or presence of both JAK2/MPL
      mutations and advanced age). Herein, we provide a point-of-care treatment
      algorithm that is risk-adapted and based on evidence and decades of experience.

PMID- 29321522
TI  - Accelerated proteomic visualization of individual predatory venoms of Conus
      purpurascens reveals separately evolved predation-evoked venom cabals.
AB  - Cone snail venoms have separately evolved for predation and defense. Despite
      remarkable inter- and intra-species variability, defined sets of synergistic
      venom peptides (cabals) are considered essential for prey capture by cone snails.
      To better understand the role of predatory cabals in cone snails, we used a high
      throughput proteomic data mining and visualisation approach. Using this approach,
      the relationship between the predatory venom peptides from nine C. purpurascens
      was systematically analysed. Surprisingly, potentially synergistic levels of
      kappa-PVIIA and delta-PVIA were only identified in five of nine specimens. In
      contrast, the remaining four specimens lacked significant levels of these known
      excitotoxins and instead contained high levels of the muscle nAChR blockers psi
      PIIIE and alphaA-PIVA. Interestingly, one of nine specimens expressed both
      cabals, suggesting that these sub-groups might represent inter-breeding sub
      species of C. purpurascens. High throughput cluster analysis also revealed these
      two cabals clustered with distinct groups of venom peptides that are presently
      uncharacterised. This is the first report showing that the cone snails of the
      same species can deploy two separate and distinct predatory cabals for prey
      capture and shows that the cabals deployed by this species can be more complex
      than presently realized. Our semi-automated proteomic analysis facilitates the
      deconvolution of complex venoms to identify co-evolved families of peptides and
      help unravel their evolutionary relationships in complex venoms.

PMID- 29321524
TI  - Phenotypic divergence despite low genetic differentiation in house sparrow
      populations.
AB  - Studying patterns of phenotypic variation among populations can shed light on the
      drivers of evolutionary processes. The house sparrow (Passer domesticus) is one
      of the world's most ubiquitous bird species, as well as a successful invader. We
      investigated phenotypic variation in house sparrow populations across a climatic
      gradient and in relation to a possible scenario of an invasion. We measured
      variation in morphological, coloration, and behavioral traits (exploratory
      behavior and neophobia) and compared it to the neutral genetic variation. We
      found that sparrows were larger and darker in northern latitudes, in accordance
      with Bergmann's and Gloger's biogeographic rules. Morphology and behavior mostly
      differed between the southernmost populations and the other regions, supporting
      the possibility of an invasion. Genetic differentiation was low and diversity
      levels were similar across populations, indicating high gene flow. Nevertheless,
      the southernmost and northern populations differed genetically to some extent.
      Furthermore, genetic differentiation (F ST) was lower in comparison to phenotypic
      variation (P ST), indicating that the phenotypic variation is shaped by
      directional selection or by phenotypic plasticity. This study expands our
      knowledge on evolutionary mechanisms and biological invasions.

PMID- 29321525
TI  - Exploring the consequences of social defeat stress and intermittent ethanol
      drinking on dopamine dynamics in the rat nucleus accumbens.
AB  - The current study aimed to explore how presynaptic dopamine (DA) function is
      altered following brief stress episodes and chronic ethanol self-administration
      and whether these neuroadaptations modify the acute effects of ethanol on DA
      dynamics. We used fast-scan cyclic voltammetry to evaluate changes in DA release
      and uptake parameters in rat nucleus accumbens brain slices by analyzing DA
      transients evoked through single pulse electrical stimulation. Adult male rats
      were divided into four groups: ethanol-naive or ethanol drinking (six week
      intermittent two-bottle choice) and stressed (mild social defeat) or nonstressed.
      Results revealed that the mild stress significantly increased DA release and
      uptake in ethanol-naive subjects, compared to nonstressed controls. Chronic
      ethanol self-administration increased the DA uptake rate and occluded the effects
      of stress on DA release dynamics. Bath-applied ethanol decreased stimulated DA
      efflux in a concentration-dependent manner in all groups; however, the magnitude
      of this effect was blunted by either stress or chronic ethanol, or by a
      combination of both procedures. Together, these findings suggest that stress and
      ethanol drinking may promote similar adaptive changes in accumbal presynaptic DA
      release measures and that these changes may contribute to the escalation in
      ethanol intake that occurs during the development of alcohol use disorder.

PMID- 29321523
TI  - Integrative genomic and transcriptomic analysis of leiomyosarcoma.
AB  - Leiomyosarcoma (LMS) is an aggressive mesenchymal malignancy with few therapeutic
      options. The mechanisms underlying LMS development, including clinically
      actionable genetic vulnerabilities, are largely unknown. Here we show, using
      whole-exome and transcriptome sequencing, that LMS tumors are characterized by
      substantial mutational heterogeneity, near-universal inactivation of TP53 and
      RB1, widespread DNA copy number alterations including chromothripsis, and
      frequent whole-genome duplication. Furthermore, we detect alternative telomere
      lengthening in 78% of cases and identify recurrent alterations in telomere
      maintenance genes such as ATRX, RBL2, and SP100, providing insight into the
      genetic basis of this mechanism. Finally, most tumors display hallmarks of
      "BRCAness", including alterations in homologous recombination DNA repair genes,
      multiple structural rearrangements, and enrichment of specific mutational
      signatures, and cultured LMS cells are sensitive towards olaparib and cisplatin.
      This comprehensive study of LMS genomics has uncovered key biological features
      that may inform future experimental research and enable the design of novel
      therapies.

PMID- 29321526
TI  - The chemical armament of reef-building corals: inter- and intra-specific
      variation and the identification of an unusual actinoporin in Stylophora
      pistilata.
AB  - Corals, like other cnidarians, are venomous animals that rely on stinging cells
      (nematocytes) and their toxins to catch prey and defend themselves against
      predators. However, little is known about the chemical arsenal employed by stony
      corals, despite their ecological importance. Here, we show large differences in
      the density of nematocysts and whole-body hemolytic activity between different
      species of reef-building corals. In the branched coral Stylophora pistillata, the
      tips of the branches exhibited a greater hemolytic activity than the bases.
      Hemolytic activity and nematocyst density were significantly lower in Stylophora
      that were maintained for close to a year in captivity compared to corals
      collected from the wild. A cysteine-containing actinoporin was identified in
      Stylophora following partial purification and tandem mass spectrometry. This
      toxin, named Delta-Pocilopotoxin-Spi1 (Delta-PCTX-Spi1) is the first hemolytic
      toxin to be partially isolated and characterized in true reef-building corals.
      Loss of hemolytic activity during chromatography suggests that this actinoporin
      is only one of potentially several hemolytic molecules. These results suggest
      that the capacity to employ offensive and defensive chemicals by corals is a
      dynamic trait within and between coral species, and provide a first step towards
      identifying the molecular components of the coral chemical armament.

PMID- 29321527
TI  - A hospital based retrospective study of factors influencing therapeutic
      leukapheresis in patients presenting with hyperleukocytic leukaemia.
AB  - Therapeutic leukapheresis is a rapid and effective method to reduce early
      mortality of patients with hyperleukocytic leukaemia (HLL). However, few studies
      on factors influencing the efficiency have been reported. In this study, 67 cases
      who underwent leukapheresis were retrospectively analysed and factors related to
      the collection efficiency of leukapheresis (CEWBC) were also evaluated. Paired t
      test showed that there was a significant decrease in statistics of white blood
      cell (WBC) counts after apheresis. The results of two independent samples
      nonparametric test suggested that WBC counts, platelet (PLT) counts, haematocrit
      (HCT), hemoglobin (HGB), serum chlorine (Cl) and globulin (GLB) before
      leukapheresis correlated with the CEWBC. Multiple linear regression analysis with
      background stepwise variable selection indicated that only WBC and HCT before
      leukapheresis had an influence on CEWBC significantly. Kaplan-Meier analysis and
      Cox regression model indicated that lymphocyte (LY) and mean corpuscular
      hemoglobin (MCH) pre-apheresis as independent factors significantly affected the
      prognostic survival of patients with HLL. Moreover, platelets and red blood cell
      were contaminated in the product of leukapheresis. It is an urgent problem to be
      solved in order to realise higher efficacy and higher purity of WBC collection to
      improve the survival of patients with HLL through optimising instruments.

PMID- 29321528
TI  - Large-scale ocean connectivity and planktonic body size.
AB  - Global patterns of planktonic diversity are mainly determined by the dispersal of
      propagules with ocean currents. However, the role that abundance and body size
      play in determining spatial patterns of diversity remains unclear. Here we
      analyse spatial community structure - beta-diversity - for several planktonic and
      nektonic organisms from prokaryotes to small mesopelagic fishes collected during
      the Malaspina 2010 Expedition. beta-diversity was compared to surface ocean
      transit times derived from a global circulation model, revealing a significant
      negative relationship that is stronger than environmental differences. Estimated
      dispersal scales for different groups show a negative correlation with body size,
      where less abundant large-bodied communities have significantly shorter dispersal
      scales and larger species spatial turnover rates than more abundant small-bodied
      plankton. Our results confirm that the dispersal scale of planktonic and micro
      nektonic organisms is determined by local abundance, which scales with body size,
      ultimately setting global spatial patterns of diversity.

PMID- 29321529
TI  - Multilayer networks reveal the spatial structure of seed-dispersal interactions
      across the Great Rift landscapes.
AB  - Species interaction networks are traditionally explored as discrete entities with
      well-defined spatial borders, an oversimplification likely impairing their
      applicability. Using a multilayer network approach, explicitly accounting for
      inter-habitat connectivity, we investigate the spatial structure of seed
      dispersal networks across the Gorongosa National Park, Mozambique. We show that
      the overall seed-dispersal network is composed by spatially explicit communities
      of dispersers spanning across habitats, functionally linking the landscape
      mosaic. Inter-habitat connectivity determines spatial structure, which cannot be
      accurately described with standard monolayer approaches either splitting or
      merging habitats. Multilayer modularity cannot be predicted by null models
      randomizing either interactions within each habitat or those linking habitats;
      however, as habitat connectivity increases, random processes become more
      important for overall structure. The importance of dispersers for the overall
      network structure is captured by multilayer versatility but not by standard
      metrics. Highly versatile species disperse many plant species across multiple
      habitats, being critical to landscape functional cohesion.

PMID- 29321530
TI  - The effect of raloxifene augmentation in men and women with a schizophrenia
      spectrum disorder: a systematic review and meta-analysis.
AB  - Recognizing the robust sex differences in schizophrenia prevalence, the selective
      estrogen receptor modulator (SERM) raloxifene is a likely candidate for
      augmentation therapy in this disorder. Therefore, a systematic search was
      performed using PubMed (Medline), Embase, PsychInfo, and Cochrane Database of
      Systematic Reviews. Randomized controlled trials investigating the effect of
      raloxifene in schizophrenia spectrum disorders were included in the quantitative
      analyses. Outcome measures were psychotic symptom severity, depression, and
      cognition. Meta-analyses were performed using Comprehensive Meta-Analysis
      software. A random-effects model was used to compute overall weighted effect
      sizes in Hedges' g. Nine studies were included, investigating 561 patients with a
      schizophrenia spectrum disorder. Raloxifene was superior to placebo in improving
      total symptom severity (N = 482; Hedge's g = .57, p = 0.009), as well as positive
      (N = 561; Hedge's g = 0.32, p = 0.02), negative (N = 561; Hedge's g = 0.40, p =
      0.02), and general (N = 526; Hedge's g = 0.46, p = 0.01) subscales, as measured
      by the Positive and Negative Syndrome Scale. No significant effects were found
      for comorbid depression and cognitive functioning. Altogether, these results
      confirm the potential of raloxifene augmentation in the treatment of
      schizophrenia.

PMID- 29321531
TI  - Biopsy Needle Integrated with Electrical Impedance Sensing Microelectrode Array
      towards Real-time Needle Guidance and Tissue Discrimination.
AB  - A biopsy needle with electrical impedance sensor array based on stainless steel
      microelectrodes (EIS needle) was developed for real-time four electrode
      measurement and multi-spot sensing of tissues during the biopsy process. The
      sensor performance was characterized by using saline solutions with various
      concentrations, which proved accurate, stable and reliable electrical impedance
      measurement. The capability of impedance-based tissue sensing was verified by the
      conductivity measurement of agarose hydrogel based phantom mimicking cancer
      tissue. Furthermore, multi-spot impedance sensing during needle insertion was
      demonstrated using porcine meat with muscle and fat layers, which exhibited a
      clear discrimination between different types of tissues. Also, the electrical
      impedance difference between normal and fatty livers of mouse model was measured
      by the EIS needle. We could successfully demonstrate that the EIS needle can
      provide localized and accurate characterization of biological tissues at the
      needle tip.

PMID- 29321532
TI  - Neural measures of the role of affective prosody in empathy for pain.
AB  - Emotional communication often needs the integration of affective prosodic and
      semantic components from speech and the speaker's facial expression. Affective
      prosody may have a special role by virtue of its dual-nature; pre-verbal on one
      side and accompanying semantic content on the other. This consideration led us to
      hypothesize that it could act transversely, encompassing a wide temporal window
      involving the processing of facial expressions and semantic content expressed by
      the speaker. This would allow powerful communication in contexts of potential
      urgency such as witnessing the speaker's physical pain. Seventeen participants
      were shown with faces preceded by verbal reports of pain. Facial expressions,
      intelligibility of the semantic content of the report (i.e., participants' mother
      tongue vs. fictional language) and the affective prosody of the report (neutral
      vs. painful) were manipulated. We monitored event-related potentials (ERPs) time
      locked to the onset of the faces as a function of semantic content
      intelligibility and affective prosody of the verbal reports. We found that
      affective prosody may interact with facial expressions and semantic content in
      two successive temporal windows, supporting its role as a transverse
      communication cue.

PMID- 29321533
TI  - Increased heart rate after exercise facilitates the processing of fearful but not
      disgusted faces.
AB  - Embodied theories of emotion assume that emotional processing is grounded in
      bodily and affective processes. Accordingly, the perception of an emotion re
      enacts congruent sensory and affective states; and conversely, bodily states
      congruent with a specific emotion facilitate emotional processing. This study
      tests whether the ability to process facial expressions (faces having a neutral
      expression, expressing fear, or disgust) can be influenced by making the
      participants' body state congruent with the expressed emotion (e.g., high heart
      rate in the case of faces expressing fear). We designed a task requiring
      participants to categorize pictures of male and female faces that either had a
      neutral expression (neutral), or expressed emotions whose linkage with high heart
      rate is strong (fear) or significantly weaker or absent (disgust). Critically,
      participants were tested in two conditions: with experimentally induced high
      heart rate (Exercise) and with normal heart rate (Normal). Participants processed
      fearful faces (but not disgusted or neutral faces) faster when they were in the
      Exercise condition than in the Normal condition. These results support the idea
      that an emotionally congruent body state facilitates the automatic processing of
      emotionally-charged stimuli and this effect is emotion-specific rather than due
      to generic factors such as arousal.

PMID- 29321534
TI  - Mitochondrial network complexity emerges from fission/fusion dynamics.
AB  - Mitochondrial networks exhibit a variety of complex behaviors, including
      coordinated cell-wide oscillations of energy states as well as a phase transition
      (depolarization) in response to oxidative stress. Since functional and structural
      properties are often interwinded, here we characterized the structure of
      mitochondrial networks in mouse embryonic fibroblasts using network tools and
      percolation theory. Subsequently we perturbed the system either by promoting the
      fusion of mitochondrial segments or by inducing mitochondrial fission.
      Quantitative analysis of mitochondrial clusters revealed that structural
      parameters of healthy mitochondria laid in between the extremes of highly
      fragmented and completely fusioned networks. We confirmed our results by
      contrasting our empirical findings with the predictions of a recently described
      computational model of mitochondrial network emergence based on fission-fusion
      kinetics. Altogether these results offer not only an objective methodology to
      parametrize the complexity of this organelle but also support the idea that
      mitochondrial networks behave as critical systems and undergo structural phase
      transitions.

PMID- 29321535
TI  - Multi-label Deep Learning for Gene Function Annotation in Cancer Pathways.
AB  - The war on cancer is progressing globally but slowly as researchers around the
      world continue to seek and discover more innovative and effective ways of curing
      this catastrophic disease. Organizing biological information, representing it,
      and making it accessible, or biocuration, is an important aspect of biomedical
      research and discovery. However, because maintaining sophisticated biocuration is
      highly resource dependent, it continues to lag behind the continually being
      generated biomedical data. Another critical aspect of cancer research, pathway
      analysis, has proven to be an efficient method for gaining insight into the
      underlying biology associated with cancer. We propose a deep-learning-based
      model, Stacked Denoising Autoencoder Multi-Label Learning (SdaMLL), for
      facilitating gene multi-function discovery and pathway completion. SdaMLL can
      capture intermediate representations robust to partial corruption of the input
      pattern and generate low-dimensional codes superior to conditional dimension
      reduction tools. Experimental results indicate that SdaMLL outperforms existing
      classical multi-label algorithms. Moreover, we found some gene functions, such as
      Fused in Sarcoma (FUS, which may be part of transcriptional misregulation in
      cancer) and p27 (which we expect will become a member viral carcinogenesis), that
      can be used to complete the related pathways. We provide a visual tool (
      https://www.keaml.cn/gpvisual ) to view the new gene functions in cancer
      pathways.

PMID- 29321536
TI  - Enzymes of the one-carbon folate metabolism as anticancer targets predicted by
      survival rate analysis.
AB  - The significance of mitochondrial metabolism in cancer cells has recently been
      gaining attention. Among other findings, One-carbon folate metabolism has been
      reported to be closely associated with cellular characteristics in cancer. To
      study molecular targets for efficient cancer therapy, we investigated the
      association between the expressions of genes that code enzymes involved in one
      carbon metabolism and survival rate of patients with adenocarcinomas of the
      colorectum and lung. Patients with high expression of genes that control the
      metabolic cycle of tetrahydrofolate (THF) in mitochondria, SHMT2, MTHFD2, and
      ALDH1L2, have a shorter overall survival rate compared with patients with low
      expression of these genes. Our results revealed that these genes could be novel
      and more promising anticancer targets than dihydrofolate reductase (DHFR), the
      current target of drug therapy linked with folate metabolism, suggesting the
      rationale of drug discovery in cancer medicine.

PMID- 29321537
TI  - Computational Investigation of Environment-Noise Interaction in Single-Cell
      Organisms: The Merit of Expression Stochasticity Depends on the Quality of
      Environmental Fluctuations.
AB  - Organisms need to adapt to changing environments and they do so by using a broad
      spectrum of strategies. These strategies include finding the right balance
      between expressing genes before or when they are needed, and adjusting the degree
      of noise inherent in gene expression. We investigated the interplay between
      different nutritional environments and the inhabiting organisms' metabolic and
      genetic adaptations by applying an evolutionary algorithm to an agent-based model
      of a concise bacterial metabolism. Our results show that constant environments
      and rapidly fluctuating environments produce similar adaptations in the
      organisms, making the predictability of the environment a major factor in
      determining optimal adaptation. We show that exploitation of expression noise
      occurs only in some types of fluctuating environment and is strongly dependent on
      the quality and availability of nutrients: stochasticity is generally detrimental
      in fluctuating environments and beneficial only at equal periods of nutrient
      availability and above a threshold environmental richness. Moreover, depending on
      the availability and nutritional value of nutrients, nutrient-dependent and
      stochastic expression are both strategies used to deal with environmental
      changes. Overall, we comprehensively characterize the interplay between the
      quality and periodicity of an environment and the resulting optimal deterministic
      and stochastic regulation strategies of nutrient-catabolizing pathways.

PMID- 29321539
TI  - Phonon laser in the coupled vector cavity optomechanics.
AB  - We presented a method to control the intensity of a phonon-laser mode (the
      vibrational excitations of a mechanical mode) by adjusting the polarization of
      the pump light based on the experimentally achievable parameters, which provides
      an additional degree of freedom to control the phonon laser action. Due to
      orthogonally polarized modes of cavity, the polarization behavior of light field
      which describes it's vector nature is introduced to control phonon laser action
      in our scheme. Compared with the traditional phonon laser scheme, polarization
      related phonon laser in the coupled vector cavity optomechanics can be
      effectively controlled without changing other parameters of the device. This
      result provides an useful approach for acquiring polarization-related phonon
      laser by on-chip optical device.

PMID- 29321540
TI  - Wide Band Low Noise Love Wave Magnetic Field Sensor System.
AB  - We present a comprehensive study of a magnetic sensor system that benefits from a
      new technique to substantially increase the magnetoelastic coupling of surface
      acoustic waves (SAW). The device uses shear horizontal acoustic surface waves
      that are guided by a fused silica layer with an amorphous magnetostrictive
      FeCoSiB thin film on top. The velocity of these so-called Love waves follows the
      magnetoelastically-induced changes of the shear modulus according to the magnetic
      field present. The SAW sensor is operated in a delay line configuration at
      approximately 150 MHz and translates the magnetic field to a time delay and a
      related phase shift. The fundamentals of this sensor concept are motivated by
      magnetic and mechanical simulations. They are experimentally verified using
      customized low-noise readout electronics. With an extremely low magnetic noise
      level of ~100 pT/[Formula: see text], a bandwidth of 50 kHz and a dynamic range
      of 120 dB, this magnetic field sensor system shows outstanding characteristics. A
      range of additional measures to further increase the sensitivity are investigated
      with simulations.

PMID- 29321538
TI  - Sweep Dynamics (SD) plots: Computational identification of selective sweeps to
      monitor the adaptation of influenza A viruses.
AB  - Monitoring changes in influenza A virus genomes is crucial to understand its
      rapid evolution and adaptation to changing conditions e.g. establishment within
      novel host species. Selective sweeps represent a rapid mode of adaptation and are
      typically observed in human influenza A viruses. We describe Sweep Dynamics (SD)
      plots, a computational method combining phylogenetic algorithms with statistical
      techniques to characterize the molecular adaptation of rapidly evolving viruses
      from longitudinal sequence data. SD plots facilitate the identification of
      selective sweeps, the time periods in which these occurred and associated changes
      providing a selective advantage to the virus. We studied the past genome-wide
      adaptation of the 2009 pandemic H1N1 influenza A (pH1N1) and seasonal H3N2
      influenza A (sH3N2) viruses. The pH1N1 influenza virus showed simultaneous amino
      acid changes in various proteins, particularly in seasons of high pH1N1 activity.
      Partially, these changes resulted in functional alterations facilitating
      sustained human-to-human transmission. In the evolution of sH3N2 influenza
      viruses, we detected changes characterizing vaccine strains, which were
      occasionally revealed in selective sweeps one season prior to the WHO
      recommendation. Taken together, SD plots allow monitoring and characterizing the
      adaptive evolution of influenza A viruses by identifying selective sweeps and
      their associated signatures.

PMID- 29321541
TI  - Identification and validation of an 18-gene signature highly-predictive of
      bladder cancer metastasis.
AB  - We found two deviant groups that were unpredictable with clinical models
      predicting bladder cancer metastasis. The group G consists of patients at high
      risk of pN+ , but they have pN0. The group P consists of patients at low risk of
      pN+ , but they have pN+ . We aimed to determine the genetic differences between
      these two groups. 1603 patients from SEER database were enrolled to build a
      multivariate model. This model was applied to patients from the TCGA database to
      distinguish groups G and P. Differentially expressed genes between the two groups
      were identified. RT-qPCR was used to validate the results in a cohort from FUSCC.
      Two deviant groups were identified both in the SEER population and the TCGA
      population. Expression of 183 genes was significantly different between the two
      groups. 18 genes achieved significant statistical power in predicting lymph node
      metastasis excluding these two deviant groups. The 18-gene signature outperformed
      3 other bladder cancer lymph node prediction tools in 2 external GEO datasets. RT
      qPCR results of our own cohort identified NECTIN2 (P = 0.036) as the only gene
      that could predict metastasis. Our study showed a novel gene screening method and
      proposed an 18-gene signature highly predictive of bladder cancer metastasis.

PMID- 29321542
TI  - Timing of spermarche and menarche among urban students in Guangzhou, China:
      trends from 2005 to 2012 and association with Obesity.
AB  - In Guangzhou, China, whether the trend of a decreasing pubertal age has continued
      in recent years remained unknown, and the association between obesity and early
      puberty was still controversial. Herein, we conducted a serial cross-sectional
      study using data from physical fitness surveillance (2005-2012), to determine the
      recent trends in age at spermarche and menarche among students in Guangzhou, and
      to investigate whether elevated BMI modified timing of spermarche and menarche.
      This study included 1,278,258 urban students. In boys, no significant differences
      were observed in median ages of spermarche (MAS) from 2005 to 2012, with
      overlapping 95% CIs. Similar results were observed for median ages of menarche
      (MAM) in girls. The Cox-Stuart trend test showed neither upward nor downward
      shift in MAS and MAM over time (P = 0.625; 1.000). Each year, both MAS and MAM
      decreased with increasing BMI. Furthermore, a higher BMI was associated with
      early age at spermarche and menarche, with ORs of 1.052 (95% CI = 1.045-1.059)
      and 1.233 (95% CI = 1.220-1.247) in 2012 for boys and girls, respectively. In
      conclusion, the pubertal timing has been stable in urban students from 2005 to
      2012. Furthermore, obesity was associated with early timing of spermarche and
      menarche.

PMID- 29321543
TI  - A new, large-bodied omnivorous bat (Noctilionoidea: Mystacinidae) reveals lost
      morphological and ecological diversity since the Miocene in New Zealand.
AB  - A new genus and species of fossil bat is described from New Zealand's only pre
      Pleistocene Cenozoic terrestrial fauna, the early Miocene St Bathans Fauna of
      Central Otago, South Island. Bayesian total evidence phylogenetic analysis places
      this new Southern Hemisphere taxon among the burrowing bats (mystacinids) of New
      Zealand and Australia, although its lower dentition also resembles Africa's
      endemic sucker-footed bats (myzopodids). As the first new bat genus to be added
      to New Zealand's fauna in more than 150 years, it provides new insight into the
      original diversity of chiropterans in Australasia. It also underscores the
      significant decline in morphological diversity that has taken place in the highly
      distinctive, semi-terrestrial bat family Mystacinidae since the Miocene. This bat
      was relatively large, with an estimated body mass of ~40 g, and its dentition
      suggests it had an omnivorous diet. Its striking dental autapomorphies, including
      development of a large hypocone, signal a shift of diet compared with other
      mystacinids, and may provide evidence of an adaptive radiation in feeding
      strategy in this group of noctilionoid bats.

PMID- 29321545
TI  - Mathematical model of salt cavern leaching for gas storage in high-insoluble salt
      formations.
AB  - A mathematical model is established to predict the salt cavern development during
      leaching in high-insoluble salt formations. The salt-brine mass transfer rate is
      introduced, and the effects of the insoluble sediments on the development of the
      cavern are included. Considering the salt mass conservation in the cavern, the
      couple equations of the cavern shape, brine concentration and brine velocity are
      derived. According to the falling and accumulating rules of the insoluble
      particles, the governing equations of the insoluble sediments are deduced. A
      computer program using VC++ language is developed to obtain the numerical
      solution of these equations. To verify the proposed model, the leaching processes
      of two salt caverns of Jintan underground gas storage are simulated by the
      program, using the actual geological and technological parameters. The same
      simulation is performed by the current mainstream leaching software in China. The
      simulation results of the two programs are compared with the available field
      data. It shows that the proposed software is more accurate on the shape
      prediction of the cavern bottom and roof, which demonstrates the reliability and
      applicability of the model.

PMID- 29321544
TI  - A Gaussian extension for Diffraction Enhanced Imaging.
AB  - Unlike conventional x-ray attenuation one of the advantages of phase contrast x
      ray imaging is its capability of extracting useful physical properties of the
      sample. In particular the possibility to obtain information from small angle
      scattering about unresolvable structures with sub-pixel resolution sensitivity
      has drawn attention for both medical and material science applications. We report
      on a novel algorithm for the analyzer based x-ray phase contrast imaging
      modality, which allows the robust separation of absorption, refraction and
      scattering effects from three measured x-ray images. This analytical approach is
      based on a simple Gaussian description of the analyzer transmission function and
      this method is capable of retrieving refraction and small angle scattering angles
      in the full angular range typical of biological samples. After a validation of
      the algorithm with a simulation code, which demonstrated the potential of this
      highly sensitive method, we have applied this theoretical framework to
      experimental data on a phantom and biological tissues obtained with synchrotron
      radiation. Owing to its extended angular acceptance range the algorithm allows
      precise assessment of local scattering distributions at biocompatible radiation
      doses, which in turn might yield a quantitative characterization tool with
      sufficient structural sensitivity on a submicron length scale.

PMID- 29321546
TI  - Tribological Properties of Ultrananocrystalline Diamond Films: Mechanochemical
      Transformation of Sliding Interfaces.
AB  - Improving the tribological properties of materials in ambient and high vacuum
      tribo-conditions is useful for inter-atmospheric applications. Highly
      hydrogenated and less-hydrogenated ultrananocrystalline diamond (UNCD) films with
      distinct microstructural characteristics were deposited on Ti-6Al-4 V alloy, by
      optimizing the plasma conditions in the chemical vapor deposition. Both the UNCD
      films showed less friction coefficient in ambient atmospheric tribo-contact
      conditions due to the passivation. This provides chemical stability to UNCD films
      under the tribo-mechanical stressed conditions which limits the transferlayer
      formation and conversion of UNCD phase into graphitization/amorphization.
      However, in the high vacuum tribo-conditions, highly-hydrogenated UNCD films
      showed low friction value which gradually increased to the higher magnitude at
      longer sliding cycles. The low friction coefficient was indicative of passivation
      provided by the hydrogen network intrinsically present in the UNCD films. It
      gradually desorbs and the dangling bonds are progressively activated in the
      contact regime, leading to a gradual increase in the friction value. In contrast,
      less-hydrogenated UNCD films do not exhibit low friction regime in high vacuum
      conditions due to the lack of internal passivation. In this case, the conversion
      of UNCD to amorphized carbon structure in the wear tracks and amorphous carbon (a
      C) tribofilm formation on ball scars were observed.

PMID- 29321547
TI  - Polycythemia vera treatment algorithm 2018.
AB  - Recently reported mature survival data have confirmed the favorable prognosis in
      polycythemia vera (PV), with an estimated median survival of 24 years, in
      patients younger than age 60 years old. Currently available drugs for PV have not
      been shown to prolong survival or alter the natural history of the disease and
      are instead indicated primarily for prevention of thrombosis. Unfortunately,
      study endpoints that are being utilized in currently ongoing clinical trials in
      PV do not necessarily target clinically or biologically relevant outcomes, such
      as thrombosis, survival, or morphologic remission, and are instead focused on
      components of disease palliation. Even more discouraging has been the lack of
      critical appraisal from "opinion leaders", on the added value of newly approved
      drugs. Keeping these issues in mind, at present, we continue to advocate
      conservative management in low-risk PV (phlebotomy combined with once- or twice
      daily aspirin therapy) and include cytoreductive therapy in "high-risk" patients;
      in the latter regard, our first, second, and third line drugs of choice are
      hydroxyurea, pegylated interferon-alpha and busulfan, respectively. In addition,
      it is reasonable to consider JAK2 inhibitor therapy, in the presence of
      protracted pruritus or markedly enlarged splenomegaly shown to be refractory to
      the aforementioned drugs.

PMID- 29321548
TI  - Role and mechanism of AT1-AA in the pathogenesis of HELLP syndrome.
AB  - HELLP syndrome remains a leading cause of maternal and neonatal mortality and
      morbidity worldwide, which symptoms include hemolysis, elevated liver enzymes and
      low platelet count. The objective of this study was to determine whether HELLP is
      associated with AT1-AA. The positive rate and titer of AT1-AA in plasma from
      pregnant women were determined, and the correlation of AT1-AA titer with the
      grade of HELLP was analyzed. A HELLP rat model established by intravenous
      injection of AT1-AA. Our experimental results show the AT1-AA titer and positive
      rate were significantly higher in HELLP group, and AT1-AA titer were positively
      correlated with the level of TNF-alpha and ET-1 in plasma and the grade of HELLP
      syndrome. The results of animal experiments showed that the typical features of
      HELLP in the pregnant rats after AT1-AA injection. The levels of TNF-alpha and ET
      1 in plasma and liver tissue were significantly increased in AT1-AA-treated rats
      compared with control rats. The HELLP syndrome induced by AT1-AA was attenuated
      markedly after administration of losartan. These data support the hypothesis that
      one the potential pathway that AT1-AA induce damage to capillary endothelial
      cells and liver during pregnancy is through activation of TNF-alpha and ET-1.

PMID- 29321549
TI  - Probing the molecular basis of hERG drug block with unnatural amino acids.
AB  - Repolarization of the cardiac action potential is primarily mediated by two
      voltage-dependent potassium currents: I Kr and I Ks . The voltage-gated potassium
      channel that gives rise to I Kr, Kv11.1 (hERG), is uniquely susceptible to high
      affinity block by a wide range of drug classes. Pore residues Tyr652 and Phe656
      are critical to potent drug interaction with hERG. It is considered that the
      molecular basis of this broad-spectrum drug block phenomenon occurs through
      interactions specific to the aromatic nature of the side chains at Tyr652 and
      Phe656. In this study, we used nonsense suppression to incorporate singly and
      doubly fluorinated phenylalanine residues at Tyr652 and Phe656 to assess cation
      pi interactions in hERG terfenadine, quinidine, and dofetilide block.
      Incorporation of these unnatural amino acids was achieved with minimal alteration
      to channel activation or inactivation gating. Our assessment of terfenadine,
      quinidine, and dofetilide block did not reveal evidence of a cation-pi
      interaction at either aromatic residue, but, interestingly, shows that certain
      fluoro-Phe substitutions at position 652 result in weaker  drug potency.

PMID- 29321550
TI  - Evaluating estimated glomerular filtration rates of creatinine and cystatin C for
      male patients with chronic spinal cord injury.
AB  - STUDY DESIGN: Retrospective study OBJECTIVES: To compare the accuracy of
      estimated serum creatinine (Cre)-based glomerular filtration rates (eGFRcre) and
      serum cystatin C (CysC)-based eGFR (eGFRcys) for determining renal function in
      patients with spinal cord injury (SCI). SETTING: Department of Urology, Tohoku
      Rosai Hospital, Japan METHODS: Male patients with SCI for longer than 5 years
      after injury were eligible for inclusion in this study. eGFRcre and eGFRcys were
      calculated using the following formulas: eGFRcre = 194 * Cre-1.094 * age-0.287;
      eGFRcys = (104 * CysC-0.1019 * 0.996age) - 8. The eGFRcre/eGFRcys ratio between
      0.8 and 1.2 was considered to be equal, and a relationship between them was
      investigated. Demographic data, degree of spinal cord damage, management of
      bladder emptying, post-injury period, and ambulatory status were evaluated.
      RESULTS: A total of 115 male patients were included. eGFRcre overestimated renal
      function in 87 (76%) patients with SCI compared with eGFRcys. On univariate
      analysis, renal function by eGFRcre was overestimated in patients with an eGFRcre
      of more than 60 ml min-1 per 1.73 m2 (P < 0.001), in non-ambulatory patients (P <
      0.001) and, in patients with complete paralysis (P < 0.001). On multivariate
      analysis, an eGFRcre of more than 60 ml min-1 per 1.73 m2 (P < 0.001), non
      ambulatory status (P < 0.001), complete paralysis (P = 0.17), and age (P < 0.001)
      were independent factors for overestimated renal function by eGFRcre.
      CONCLUSIONS: eGFRcre overestimates renal function compared with eGFRcys. eGFRcys
      is beneficial, particularly in patients with an eGFRcre of more than 60 ml min-1
      per 1.73 m2, in non-ambulatory patients, and in older patients with SCI.

PMID- 29321551
TI  - Aster leafhopper survival and reproduction, and Aster yellows transmission under
      static and fluctuating temperatures, using ddPCR for phytoplasma quantification.
AB  - Aster yellows (AY) is an important disease of Brassica crops and is caused by
      Candidatus Phytoplasma asteris and transmitted by the insect vector, Aster
      leafhopper (Macrosteles quadrilineatus). Phytoplasma-infected Aster leafhoppers
      were incubated at various constant and fluctuating temperatures ranging from 0 to
      35  degrees C with the reproductive host plant barley (Hordium vulgare). At 0 
      degrees C, leafhopper adults survived for 18 days, but failed to reproduce,
      whereas at 35  degrees C insects died within 18 days, but successfully reproduced
      before dying. Temperature fluctuation increased thermal tolerance in leafhoppers
      at 25  degrees C and increased fecundity of leafhoppers at 5 and 20  degrees C.
      Leafhopper adults successfully infected and produced AY-symptoms in canola plants
      after incubating for 18 days at 0-20  degrees C on barley, indicating that AY
      phytoplasma maintains its virulence in this temperature range. The presence and
      number of AY-phytoplasma in insects and plants were confirmed by droplet digital
      PCR (ddPCR) quantification. The number of phytoplasma in leafhoppers increased
      over time, but did not differ among temperatures. The temperatures associated
      with a typical crop growing season on the Canadian Prairies will not limit the
      spread of AY disease by their predominant insect vector. Also, ddPCR
      quantification is a useful tool for early detection and accurate quantification
      of phytoplasma in plants and insects.

PMID- 29321552
TI  - Random telegraph noise from resonant tunnelling at low temperatures.
AB  - The Random Telegraph Noise (RTN) in an advanced Metal-Oxide-Semiconductor Field
      Effect Transistor (MOSFET) is considered to be triggered by just one electron or
      one hole, and its importance is recognised upon the aggressive scaling. However,
      the detailed nature of the charge trap remains to be investigated due to the
      difficulty to find out the exact device, which shows the RTN feature over
      statistical variations. Here, we show the RTN can be observed from virtually all
      devices at low temperatures, and provide a methodology to enable a systematic way
      to identify the bias conditions to observe the RTN. We found that the RTN was
      observed at the verge of the Coulomb blockade in the stability diagram of a
      parasitic Single-Hole-Transistor (SHT), and we have successfully identified the
      locations of the charge traps by measuring the bias dependence of the RTN.

PMID- 29321553
TI  - Prediction of co-expression genes and integrative analysis of gene microarray and
      proteomics profile of Keshan disease.
AB  - Keshan disease (KD) is a kind of endemic cardiomyopathy which has a high
      mortality. However, molecular mechanism in the pathogenesis of KD remains poorly
      understood. Serum samples were collected from 112 KD patients and 112 normal
      controls. Gene microarray was used to screen differently expressed genes.
      Genevestigator was applied to forecast co-expression genes of significant gene.
      iTRAQ proteomics analysis was used to verify significant genes and their co
      expression genes. GO, COG, IPA and STRING were applied to undertake function
      categorization, pathway and network analysis separately. We identified 32
      differentially expressed genes; IDH2, FEM1A, SSPB1 and their respective 30 co
      expression genes; 68 differential proteins in KD. Significant proteins were
      categorized into 23 biological processes, 16 molecular functions, 16 cellular
      components, 15 function classes, 13 KD pathways and 1 network. IDH2, FEM1A,
      SSBP1, CALR, NDUFS2, IDH3A, GAPDH, TCA Cycle II (Eukaryotic) pathway and NADP
      repair pathway may play important roles in the pathogenesis of KD.

PMID- 29321554
TI  - Mutations in DNMT3A, U2AF1, and EZH2 identify intermediate-risk acute myeloid
      leukemia patients with poor outcome after CR1.
AB  - Intermediate-risk acute myeloid leukemia (IR-AML) is a clinically heterogeneous
      disease, for which optimal post-remission therapy is debated. The utility of next
      generation sequencing information in decision making for IR-AML has yet to be
      elucidated. We retrospectively studied 100 IR-AML patients, defined by European
      Leukemia Net classification, who had mutational information at diagnosis,
      received intensive chemotherapy and achieved complete remission (CR) at Cleveland
      Clinic (CC). The Cancer Genome Atlas (TCGA) data were used for validation. In the
      CC cohort, median age was 58.5 years, 64% had normal cytogenetics, and 31%
      required >1 induction cycles to achieve CR1. In univariable analysis, patients
      carrying mutations in DNMT3A, U2AF1, and EZH2 had worse overall and relapse-free
      survival. After adjusting for other variables, the presence of these mutations
      maintained an independent effect on survival in both CC and TCGA cohorts.
      Patients who did not have the mutations and underwent hematopoietic cell
      transplant (HCT) had the best outcomes. HCT improved outcomes for patients who
      had these mutations. RUNX1 or ASXL1 mutations did not predict survival, and
      performance of HCT did not confer a significant survival benefit. Our results
      provide evidence of clinical utility in considering mutation screening to
      stratify IR-AML patients after CR1 to guide therapeutic decisions.

PMID- 29321556
TI  - The Water-Alkane Interface at Various NaCl Salt Concentrations: A Molecular
      Dynamics Study of the Readily Available Force Fields.
AB  - In this study, classical molecular dynamic simulations have been used to examine
      the molecular properties of the water-alkane interface at various NaCl salt
      concentrations (up to 3.0 mol/kg). A variety of different force field
      combinations have been compared against experimental surface/interfacial tension
      values for the water-vapour, decane-vapour and water-decane interfaces. Six
      different force fields for water (SPC, SPC/E, TIP3P, TIP3Pcharmm, TIP4P &
      TIP4P2005), and three further force fields for alkane (TraPPE-UA, CGenFF & OPLS)
      have been compared to experimental data. CGenFF, OPLS-AA and TraPPE-UA all
      accurately reproduce the interfacial properties of decane. The TIP4P2005 (four
      point) water model is shown to be the most accurate water model for predicting
      the interfacial properties of water. The SPC/E water model is the best three
      point parameterisation of water for this purpose. The CGenFF and TraPPE
      parameterisations of oil accurately reproduce the interfacial tension with water
      using either the TIP4P2005 or SPC/E water model. The salinity dependence on
      surface/interfacial tension is accurately captured using the Smith & Dang
      parameterisation of NaCl. We observe that the Smith & Dang model slightly
      overestimates the surface/interfacial tensions at higher salinities (>1.5
      mol/kg). This is ascribed to an overestimation of the ion exclusion at the
      interface.

PMID- 29321555
TI  - Fourier Transform Infrared Microscopy Enables Guidance of Automated Mass
      Spectrometry Imaging to Predefined Tissue Morphologies.
AB  - Multimodal imaging combines complementary platforms for spatially resolved tissue
      analysis that are poised for application in life science and personalized
      medicine. Unlike established clinical in vivo multimodality imaging, automated
      workflows for in-depth multimodal molecular ex vivo tissue analysis that combine
      the speed and ease of spectroscopic imaging with molecular details provided by
      mass spectrometry imaging (MSI) are lagging behind. Here, we present an
      integrated approach that utilizes non-destructive Fourier transform infrared
      (FTIR) microscopy and matrix assisted laser desorption/ionization (MALDI) MSI for
      analysing single-slide tissue specimen. We show that FTIR microscopy can
      automatically guide high-resolution MSI data acquisition and interpretation
      without requiring prior histopathological tissue annotation, thus circumventing
      potential human-annotation-bias while achieving >90% reductions of data load and
      acquisition time. We apply FTIR imaging as an upstream modality to improve
      accuracy of tissue-morphology detection and to retrieve diagnostic molecular
      signatures in an automated, unbiased and spatially aware manner. We show the
      general applicability of multimodal FTIR-guided MALDI-MSI by demonstrating
      precise tumor localization in mouse brain bearing glioma xenografts and in human
      primary gastrointestinal stromal tumors. Finally, the presented multimodal tissue
      analysis method allows for morphology-sensitive lipid signature retrieval from
      brains of mice suffering from lipidosis caused by Niemann-Pick type C disease.

PMID- 29321557
TI  - Haptic shape discrimination and interhemispheric communication.
AB  - In three experiments participants haptically discriminated object shape using
      unimanual (single hand explored two objects) and bimanual exploration (both hands
      were used, but each hand, left or right, explored a separate object). Such haptic
      exploration (one versus two hands) requires somatosensory processing in either
      only one or both cerebral hemispheres; previous studies related to the perception
      of shape/curvature found superior performance for unimanual exploration,
      indicating that shape comparison is more effective when only one hemisphere is
      utilized. The current results, obtained for naturally shaped solid objects (bell
      peppers, Capsicum annuum) and simple cylindrical surfaces demonstrate otherwise:
      bimanual haptic exploration can be as effective as unimanual exploration, showing
      that there is no necessary reduction in ability when haptic shape comparison
      requires interhemispheric communication. We found that while successive bimanual
      exploration produced high shape discriminability, the participants' bimanual
      performance deteriorated for simultaneous shape comparisons. This outcome
      suggests that either interhemispheric interference or the need to attend to
      multiple objects simultaneously reduces shape discrimination ability. The current
      results also reveal a significant effect of age: older adults' shape
      discrimination abilities are moderately reduced relative to younger adults,
      regardless of how objects are manipulated (left hand only, right hand only, or
      bimanual exploration).

PMID- 29321558
TI  - Membrane shape-mediated wave propagation of cortical protein dynamics.
AB  - Immune cells exhibit stimulation-dependent traveling waves in the cortex, much
      faster than typical cortical actin waves. These waves reflect rhythmic assembly
      of both actin machinery and peripheral membrane proteins such as F-BAR domain
      containing proteins. Combining theory and experiments, we develop a
      mechanochemical feedback model involving membrane shape changes and F-BAR
      proteins that render the cortex an interesting dynamical system. We show that
      such cortical dynamics manifests itself as ultrafast traveling waves of cortical
      proteins, in which the curvature sensitivity-driven feedback always constrains
      protein lateral diffusion in wave propagation. The resulting protein wave
      propagation mainly reflects the spatial gradient in the timing of local protein
      recruitment from cytoplasm. We provide evidence that membrane undulations
      accompany these protein waves and potentiate their propagation. Therefore,
      membrane shape change and protein curvature sensitivity may have underappreciated
      roles in setting high-speed cortical signal transduction rhythms.

PMID- 29321559
TI  - The Role Of Parafacial Neurons In The Control Of Breathing During Exercise.
AB  - Neuronal cell groups residing within the retrotrapezoid nucleus (RTN) and C1 area
      of the rostral ventrolateral medulla oblongata contribute to the maintenance of
      resting respiratory activity and arterial blood pressure, and play an important
      role in the development of cardiorespiratory responses to metabolic challenges
      (such as hypercapnia and hypoxia). In rats, acute silencing of neurons within the
      parafacial region which includes the RTN and the rostral aspect of the C1 circuit
      (pFRTN/C1), transduced to express HM4D (Gi-coupled) receptors, was found to
      dramatically reduce exercise capacity (by 60%), determined by an intensity
      controlled treadmill running test. In a model of simulated exercise (electrical
      stimulation of the sciatic or femoral nerve in urethane anaesthetised
      spontaneously breathing rats) silencing of the pFRTN/C1 neurons had no effect on
      cardiovascular changes, but significantly reduced the respiratory response during
      steady state exercise. These results identify a neuronal cell group in the lower
      brainstem which is critically important for the development of the respiratory
      response to exercise and, determines exercise capacity.

PMID- 29321560
TI  - Role of cobalt cations in short range antiferromagnetic Co3O4 nanoparticles: a
      thermal treatment approach to affecting phonon and magnetic properties.
AB  - We report the phonon and magnetic properties of various well-stabilized Co3O4
      nanoparticles. The net valence in cobalt (II)/(III) cation can be obtained by
      subtracting the Co2+ ions in tetrahedral interstices and Co3+ ions in the
      octahedral interstices, respectively, which will possess spatial inhomogeneity of
      its magnetic moment via Co2+ in tetrahedra and Co3+ in octahedral configurations
      in the normal spinel structure. Furthermore, the distribution of Co2+/Co3+
      governed by various external (magnetic field and temperature) and internal
      (particle size and slightly distorted CoO6 octahedra) sources, have led to
      phenomena such as a large redshift of phonon-phonon interaction and short-range
      magnetic correlation in the inverse spinel structure. The outcome of our study is
      important in terms of the future development of magnetic semiconductor spintronic
      devices of Co3O4.

PMID- 29321561
TI  - Tumor suppressor activity of miR-451: Identification of CARF as a new target.
AB  - microRNAs (miRs) have recently emerged as small non-coding regulators of gene
      expression. We performed a loss-of-function screening by recruiting retrovirus
      mediated arbitrary manipulation of genome coupled with escape of cells from 5-Aza
      2'-deoxycytidine (5-Aza-dC)-induced senescence. miRNA pool from cells that
      emerged from 5-Aza-dC-induced senescence was subjected to miR-microarray analysis
      with respect to the untreated control. We identified miR-451 as one of the
      upregulated miRs and characterized its functional relevance to drug resistance,
      cell growth, tumor suppressor proteins p53 and pRb, and stress response. We
      report that miR-451 caused growth arrest in cells leading to their resistance to
      5-Aza-dC-induced senescence. Decrease in cyclin D1, CDK4 and phosphorylated pRB
      supported the growth arrest in miR-451 transfected cells. We demonstrate that
      Collaborator of ARF (CARF) protein is a new target of miR-451 that intermediates
      its function in tumor suppressor and stress signaling.

PMID- 29321562
TI  - Perception during double-step saccades.
AB  - How the visual system achieves perceptual stability across saccadic eye movements
      is a long-standing question in neuroscience. It has been proposed that an
      efference copy informs vision about upcoming saccades, and this might lead to
      shifting spatial coordinates and suppressing image motion. Here we ask whether
      these two aspects of visual stability are interdependent or may be dissociated
      under special conditions. We study a memory-guided double-step saccade task,
      where two saccades are executed in quick succession. Previous studies have led to
      the hypothesis that in this paradigm the two saccades are planned in parallel,
      with a single efference copy signal generated at the start of the double-step
      sequence, i.e. before the first saccade. In line with this hypothesis, we find
      that visual stability is impaired during the second saccade, which is consistent
      with (accurate) efference copy information being unavailable during the second
      saccade. However, we find that saccadic suppression is normal during the second
      saccade. Thus, the second saccade of a double-step sequence instantiates a
      dissociation between visual stability and saccadic suppression: stability is
      impaired even though suppression is strong.

PMID- 29321564
TI  - Spin-coupling-induced Improper Polarizations and Latent Magnetization in
      Multiferroic BiFeO3.
AB  - Multiferroic BiFeO3 (BFO) that exhibits a gigantic off-centering polarization
      (OCP) is the most extensively studied material among all multiferroics. In
      addition to this gigantic OCP, the BFO having R3c structural symmetry is expected
      to exhibit a couple of parasitic improper polarizations owing to coexisting spin
      polarization coupling mechanisms. However, these improper polarizations are not
      yet theoretically quantified. Herein, we show that there exist two distinct spin
      coupling-induced improper polarizations in the R3c BFO on the basis of the Landau
      Lifshitz-Ginzburg theory: DeltaP LF arising from the Lifshitz gradient coupling
      in a cycloidal spin-density wave, and DeltaP ms originating from the biquadratic
      magnetostrictive interaction. With the help of ab initio calculations, we have
      numerically evaluated magnitudes of these improper polarizations, in addition to
      the estimate of all three relevant coupling constants. We further predict that
      the magnetic susceptibility increases substantially upon the transition from the
      bulk R3c BFO to the homogeneous canted spin state in a constrained epitaxial
      film, which satisfactorily accounts for the experimental observation. The present
      study will help us understand the magnetoelectric coupling and shed light on
      design of BFO-based materials with improved multiferroic properties.

PMID- 29321563
TI  - Probiotic activities of Rhizobium laguerreae on growth and quality of spinach.
AB  - The growing interest in a healthy lifestyle and in environmental protection is
      changing habits regarding food consumption and agricultural practices. Good
      agricultural practice is indispensable, particularly for raw vegetables, and can
      include the use of plant probiotic bacteria for the purpose of biofertilization.
      In this work we analysed the probiotic potential of the rhizobial strain PEPV40,
      identified as Rhizobium laguerreae through the analysis of the recA and atpD
      genes, on the growth of spinach plants. This strain presents several in vitro
      plant growth promotion mechanisms, such as phosphate solubilisation and the
      production of indole acetic acid and siderophores. The strain PEPV40 produces
      cellulose and forms biofilms on abiotic surfaces. GFP labelling of this strain
      showed that PEPV40 colonizes the roots of spinach plants, forming microcolonies
      typical of biofilm initiation. Inoculation with this strain significantly
      increases several vegetative parameters such as leaf number, size and weight, as
      well as chlorophyll and nitrogen contents. Therefore, our findings indicate, for
      the first time, that Rhizobium laguerreae is an excellent plant probiotic, which
      increases the yield and quality of spinach, a vegetable that is increasingly
      being consumed raw worldwide.

PMID- 29321565
TI  - Characterization of novel endo-beta-N-acetylglucosaminidases from
      Sphingobacterium species, Beauveria bassiana and Cordyceps militaris that
      specifically hydrolyze fucose-containing oligosaccharides and human IgG.
AB  - Endo-beta-N-acetylglucosaminidase (ENGase) catalyzes hydrolysis of N-linked
      oligosaccharides. Although many ENGases have been characterized from various
      organisms, so far no fucose-containing oligosaccharides-specific ENGase has been
      identified in any organism. Here, we screened soil samples, using dansyl chloride
      (Dns)-labeled sialylglycan (Dns-SG) as a substrate, and discovered a strain that
      exhibits ENGase activity in the culture supernatant; this strain, named here as
      strain HMA12, was identified as a Sphingobacterium species by 16S ribosomal RNA
      gene analysis. By draft genome sequencing, five candidate ENGase encoding genes
      were identified in the genome of this strain. Recombinant proteins, purified from
      Escherichia coli expressing candidate genes ORF1152, ORF1188, ORF3046 and ORF3750
      exhibited fucose-containing oligosaccharides-specific ENGase activity. These
      ENGases exhibited optimum activities at very acidic pHs (between pH 2.3-2.5).
      BLAST searches using sequences of these candidate genes identified two fungal
      homologs of ORF1188, one in Beauveria bassiana and the other in Cordyceps
      militaris. Recombinant ORF1188, Beauveria and Cordyceps ENGases released the
      fucose-containing oligosaccharides residues from rituximab (immunoglobulin G) but
      not the high-mannose-containing oligosaccharides residues from RNase B, a result
      that not only confirmed the substrate specificity of these novel ENGases but also
      suggested that natural glycoproteins could be their substrates.

PMID- 29321567
TI  - Structure and elasticity of bush and brush-like models of the endothelial
      glycocalyx.
AB  - The endothelial glycocalyx (EG), a sugar-rich layer that lines the luminal
      surface of blood vessels, is an important constituent of the vascular system.
      Although the chemical composition of the EG is fairly well known, there is no
      consensus regarding its ultrastructure. While previous experiments probed the
      properties of the layer at the continuum level, they did not provide sufficient
      insight into its molecular organisation. In this work, we investigate the EG
      mechanics using two simple brush and bush-like simulation models, and use these
      models to describe its molecular structure and elastic response to indentation.
      We analyse the relationship between the mechanical properties of the EG layer and
      several molecular parameters, including the filament bending rigidity, grafting
      density, and the type of ultrastructure . We show that variations in the glycan
      density determine the elasticity of the EG for small deformations, and that the
      normal stress may be effectively dampened by the EG layer, preventing the stress
      from being transferred to the cell membrane. Furthermore, our bush-like model
      allows us to evaluate the forces and energies required to overcome the mechanical
      resistance of the EG.

PMID- 29321566
TI  - N-domain of angiotensin-converting enzyme hydrolyzes human and rat amyloid-beta(1
      16) peptides as arginine specific endopeptidase potentially enhancing risk of
      Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder. Amyloid
      beta (Abeta) aggregation is likely to be the major cause of AD. In contrast to
      humans and other mammals, that share the same Abeta sequence, rats and mice are
      invulnerable to AD-like neurodegenerative pathologies, and Abeta of these rodents
      (ratAbeta) has three amino acid substitutions in the metal-binding domain 1-16
      (MBD). Angiotensin-converting enzyme (ACE) cleaves Abeta-derived peptide
      substrates, however, there are contradictions concerning the localization of the
      cleavage sites within Abeta and the roles of each of the two ACE catalytically
      active domains in the hydrolysis. In the current study by using mass spectrometry
      and molecular modelling we have tested a set of peptides corresponding to MBDs of
      Abeta and ratAbeta to get insights on the interactions between ACE and these
      Abeta species. It has been shown that the N-domain of ACE (N-ACE) acts as an
      arginine specific endopeptidase on the Abeta and ratAbeta MBDs with C-amidated
      termini, thus assuming that full-length Abeta and ratAbeta can be hydrolyzed by N
      ACE in the same endopeptidase mode. Taken together with the recent data on the
      molecular mechanism of zinc-dependent oligomerization of Abeta, our results
      suggest a modulating role of N-ACE in AD pathogenesis.

PMID- 29321568
TI  - Characterization of the Cry1Ah resistance in Asian corn Borer and its cross
      resistance to other Bacillus thuringiensis toxins.
AB  - Transgenic crops producing insecticidal proteins are effective to manage
      lepidopteran pests. Development of insect-resistance is the major threat to
      Bacillus thuringiensis (Bt) crops such as Cry1Ah-Maize. Laboratory selection with
      Bt-Cry1Ah toxin incorporated in artificial diet, during 48 generations of Asian
      corn borer (ACB) Ostrinia furnacalis produced 200-fold resistance. This resistant
      colony ACB-AhR readily consumed and survived on Cry1Ah-expressing Bt-maize. Cross
      resistance analysis showed high cross-resistance to Cry1F (464-fold), moderate
      cross-resistance to Cry1Ab (28.38-fold), Cry1Ac (22.11-fold) and no cross
      resistance to Cry1Ie toxin. This ACB-AhR cross-resistant phenotype is different
      from ACB-Cry1Fa resistant population that showed no cross resistance to Cry1Ah,
      suggesting that different mechanisms of resistance were selected in these two
      populations. Bioassays of reciprocal F1 crosses-progeny suggested autosomal
      inheritance of Cry1Ah resistance with no maternal effects. The dominance of
      resistance increased as concentration decreased. In Cry1Ah-maize tissues the
      progeny of reciprocal F1 crosses behaved as functionally recessive. Progenies
      analysis from backcrosses (F1 * resistant strain) suggested polygenic
      contribution to Cry1Ah- resistance in ACB-AhR. The use of multiple toxins is an
      imperative factor for delaying evolution of resistance to Cry1Ah-corn in ACB.
      However, the fact that ACB-AhR showed cross resistance to Cry1Fa indicates that
      selection of toxins for pyramided plants should be carefully done.

PMID- 29321569
TI  - Xeno-free pre-vascularized spheroids for therapeutic applications.
AB  - Spheroid culture has gained increasing popularity, arising as a promising tool
      for regenerative medicine applications. Importantly, spheroids may present
      advantages over single-cell suspensions in cell-based therapies (CT).
      Unfortunately, most growth media used for spheroid culture contain animal origin
      components, such as fetal bovine serum (FBS). The presence of FBS compromises the
      safety of CT and presents economic and ethical constraints. SCC (supplement for
      cell culture) is a novel xeno-free (XF) industrial cell culture supplement,
      derived from well-controlled pooled human plasma and processed under good
      manufacturing practice rules. Here, we developed a XF SCC-based formulation for
      2D-culture of outgrowth endothelial cells (OEC), and then used it for generating
      co-culture spheroids of OEC and mesenchymal stem cells (MSC). XF MSC-OEC
      spheroids were characterized in detail and compared to spheroids cultured in FBS
      supplemented medium. XF spheroids presented comparable integrity, size and
      morphology as the reference culture. The use of both media resulted in spheroids
      with similar structure, abundant extracellular matrix deposition and specific
      patterns of OEC distribution and organization. Notably, XF spheroids presented
      significantly enhanced angiogenic potential, both in vitro (fibrin sprouting
      assay) and in vivo (CAM assay). These findings are particularly promising in the
      context of potential therapeutic applications.

PMID- 29321570
TI  - Transfer of a bla CTX-M-1-carrying plasmid between different Escherichia coli
      strains within the human gut explored by whole genome sequencing analyses.
AB  - Horizontal transfer of antibiotic resistance determinants contributes to
      dissemination of antibiotic resistance. Such transfer of resistance genes within
      the human gut has been documented in some in vivo studies. The present study
      investigated seven bla CTX-M-1-carrying Escherichia coli isolates from three
      consecutive faecal samples collected from one cystic fibrosis patient in a nine
      months period, by analysing whole genome sequencing data. The analyses showed
      that the seven E. coli isolates represented three genetically diverse strains.
      All isolates contained bla CTX-M-1-carrying Incl1 plasmids that shared a common
      101 kb backbone differing by only four SNPs. The plasmids harboured by the three
      different E. coli strains varied within limited regions suggestive of
      recombination events, according to the phylogenetic topology of the genomes of
      the isolates harbouring them. The findings strongly suggest that horizontal
      transfer of a bla CTX-M-1-carrying plasmid had occurred within the patient's gut.
      The study illustrates the within-host diversity of faecally carried resistant E.
      coli isolates and highlights the value of collecting multiple bacterial colonies
      from longitudinally collected samples to assess faecal carriage of resistant
      enterobacteria. The clustering of the plasmids with the corresponding E. coli
      strains carrying them indicates that the plasmids appear to have adapted to their
      respective E. coli hosts.

PMID- 29321571
TI  - Thrombin@Fe3O4 nanoparticles for use as a hemostatic agent in internal bleeding.
AB  - Bleeding remains one of the main causes of premature mortality at present, with
      internal bleeding being the most dangerous case. In this paper, magnetic
      hemostatic nanoparticles are shown for the first time to assist in minimally
      invasive treatment of internal bleeding, implying the introduction directly into
      the circulatory system followed by localization in the bleeding zone due to the
      application of an external magnetic field. Nanoparticles were produced by
      entrapping human thrombin (THR) into a sol-gel derived magnetite matrix followed
      by grinding to sizes below 200 nm and subsequent colloidization. Prepared
      colloids show protrombotic activity and cause plasma coagulation in in vitro
      experiments. We also show here using a model blood vessel that the THR@ferria
      composite does not cause systematic thrombosis due to low activity, but being
      concentrated by an external magnetic field with simultaneous fibrinogen injection
      accelerates local hemostasis and stops the bleeding. For instance, a model vessel
      system with circulating blood at the puncture of the vessel wall and the
      application of a permanent magnetic field yielded a hemostasis time by a factor
      of 6.5 shorter than that observed for the control sample. Biocompatibility of
      composites was tested on HELF and HeLa cells and revealed no toxic effects.

PMID- 29321572
TI  - Specific inhibition of acetylcholinesterase as an approach to decrease muscarinic
      side effects during myasthenia gravis treatment.
AB  - Non-selective inhibitors of cholinesterases (ChEs) are clinically used for
      treatment of myasthenia gravis (MG). While being generally safe, they cause
      numerous adverse effects including induction of hyperactivity of urinary bladder
      and intestines affecting quality of patients life. In this study we have compared
      two ChEs inhibitors, a newly synthesized compound C547 and clinically used
      pyridostigmine bromide, by their efficiency to reduce muscle weakness symptoms
      and ability to activate contractions of urinary bladder in a rat model of
      autoimmune MG. We found that at dose effectively reducing MG symptoms, C547 did
      not affect activity of rat urinary bladder. In contrast, at equipotent dose,
      pyridostigmine caused a significant increase in tonus and force of spontaneous
      contractions of bladder wall. We also found that this profile of ChEs inhibitors
      translates into the preparation of human urinary bladder. The difference in
      action observed for C547 and pyridostigmine we attribute to a high level of
      pharmacological selectivity of C547 in inhibiting acetylcholinesterase as
      compared to butyrylcholinesterase. These results raise reasonable hope that
      selective acetylcholinesterase inhibitors should show efficacy in treating MG in
      human patients with a significant reduction in adverse effects related to
      hyperactivation of smooth muscles.

PMID- 29321573
TI  - Correlation of Gli1 and HER2 expression in gastric cancer: Identification of
      novel target.
AB  - HER2 becomes the standard of care for guiding adjuvant treatment of gastric
      cancer with trastuzumab in recent years. However, the usage of this target agent
      is still limited because of the resistance to trastuzumab or the negative
      expression of HER2 in tumor tissues. The Gli1 and HER2 both play an important
      role in the pathogenesis of gastric cancer. However, the correlation of them is
      still unclear. Here we found Gli1 and HER2 are highly expressed in gastric cancer
      tissues, and they are positively related. Next, we found Gli1 positive patients
      live a shorter survival time no matter HER2 positive or negative. Furthermore,
      univariate and multivariate analysis revealed that venous invasion, HER2
      expression, Gli1 expression were independent prognostic factors for the survival
      time in gastric cancer. In addition, suppressing the expression level of Gli1 can
      decrease the cell viability and migration ability in cells and subcutaneous
      tumors. Finally, we found that HER2 may regulate Gli1 by Akt-mTOR-p70S6K pathway.
      Inhibit of HER2 and SMO have synergistic effect on reduction of cell viability.
      In conclusion, Gli1 is a favorable prognostic indicator in gastric cancer. As a
      novel target, Gli1 worth further study, especially in Her2-targeted therapy
      resistant cancers.

PMID- 29321574
TI  - Impact of climate change and human activity on soil landscapes over the past
      12,300 years.
AB  - Soils are key to ecosystems and human societies, and their critical importance
      requires a better understanding of how they evolve through time. However,
      identifying the role of natural climate change versus human activity (e.g.
      agriculture) on soil evolution is difficult. Here we show that for most of the
      past 12,300 years soil erosion and development were impacted differently by
      natural climate variability, as recorded by sediments deposited in Lake Dojran
      (Macedonia/Greece): short-lived ( < 1,000 years) climatic shifts had no effect on
      soil development but impacted soil erosion. This decoupling disappeared between
      3,500 and 3,100 years ago, when the sedimentary record suggests an unprecedented
      erosion event associated with the development of agriculture in the region. Our
      results show unambiguously how differently soils evolved under natural climate
      variability (between 12,300 and 3,500 years ago) and later in response to
      intensifying human impact. The transition from natural to anthropogenic landscape
      started just before, or at, the onset of the Greek 'Dark Ages' (~3,200 cal yr
      BP). This could represent the earliest recorded sign of a negative feedback
      between civilization and environmental impact, where the development of
      agriculture impacted soil resources, which in turn resulted in a slowdown of
      civilization expansion.

PMID- 29321575
TI  - A Complex Network Approach for the Estimation of the Energy Demand of Electric
      Mobility.
AB  - We study how renewable energy impacts regional infrastructures considering the
      full deployment of electric mobility at that scale. We use the Sardinia Island in
      Italy as a paradigmatic case study of a semi-closed system both by energy and
      mobility point of view. Human mobility patterns are estimated by means of census
      data listing the mobility dynamics of about 700,000 vehicles, the energy demand
      is estimated by modeling the charging behavior of electric vehicle owners. Here
      we show that current renewable energy production of Sardinia is able to sustain
      the commuter mobility even in the theoretical case of a full switch from internal
      combustion vehicles to electric ones. Centrality measures from network theory on
      the reconstructed network of commuter trips allows to identify the most important
      areas (hubs) involved in regional mobility. The analysis of the expected energy
      flows reveals long-range effects on infrastructures outside metropolitan areas
      and points out that the most relevant unbalances are caused by spatial
      segregation between production and consumption areas. Finally, results suggest
      the adoption of planning actions supporting the installation of renewable energy
      plants in areas mostly involved by the commuting mobility, avoiding spatial
      segregation between consumption and generation areas.

PMID- 29321576
TI  - The Microwell-mesh: A high-throughput 3D prostate cancer spheroid and drug
      testing platform.
AB  - Treatment following early diagnosis of Prostate cancer (PCa) is increasingly
      successful, whilst the treatment of advanced and metastatic PCa remains
      challenging. A major limitation in the development of new therapies is the
      prediction of drug efficacy using in vitro models. Classic in vitro 2-dimensional
      (2D) cell monolayer cultures are hypersensitive to anti-cancer drugs. As a
      result, there has been a surge in the development of platforms that enable three
      dimensional (3D) cultures thought to better replicate natural physiology and
      better predict drug efficacy. A deficiency associated with most 3D culture
      systems is that their complexity reduces the number of replicates and combination
      therapies that can be feasibly evaluated. Herein, we describe the use of a
      microwell platform that utilises a nylon mesh to retain 3D micro-tumours in
      discrete microwells; termed the Microwell-mesh. The Microwell-mesh enables the
      manufacture of ~150 micro-tumours per well in a 48-well plate, and response to
      anti-tumour drugs can be readily quantified. Our results demonstrate that 3D
      micro-tumours, unlike 2D monolayers, are not hypersensitive to Docetaxel or
      Abiraterone Acetate, providing a superior platform for the evaluation of
      sequential drug treatment. In summary, the Microwell-mesh provides an efficient
      3D micro-tumour platform for single and sequential drug screening.

PMID- 29321577
TI  - 8u, a pro-apoptosis/cell cycle arrest compound, suppresses invasion and
      metastasis through HSP90alpha downregulating and PI3K/Akt inactivation in
      hepatocellular carcinoma cells.
AB  - 8u, an acridine derivative, has been proved effective anti-hepatocarcinoma
      effect, while the underlying mechanism remains unclear. Here, metabolomics and
      proteomics approaches were applied to study its anti-cancer mechanism and explore
      its effect on HepG2 cells' invasion and metastasis abilities. The results showed
      that 8u significantly suppressed HepG2 cells migration and enhanced cell-to-cell
      junctions. The inhibition effect of 8u on invasion and metastasis disappeared
      after HSP90alpha gene silencing, and was reversed after HSP90alpha
      overexpression. The biological experimental results indicated that 8u also
      blocked PI3K/Akt pathway, thereby reducing fatty acid synthase (FASN) protein
      expression and disordering intracellular lipid metabolism to inhibit cell
      invasion and metastasis. In addition, HSP90alpha protein and PI3K/Akt pathway
      could co-adjust to each other. These findings demonstrated that 8u could
      efficiently suppress the invasion and metastasis of HepG2 cells by decreasing the
      expression of HSP90alpha protein and inhibiting the PI3K/Akt signaling pathway,
      which could be used as a potential candidate for the treatment of HCC.

PMID- 29321578
TI  - Distinction of Plasmodium ovale wallikeri and Plasmodium ovale curtisi using
      quantitative Polymerase Chain Reaction with High Resolution Melting revelation.
AB  - Plasmodium ovale curtisi (Poc) and Plasmodium ovale wallikeri (Pow) have been
      described as two distinct species, only distinguishable by molecular methods such
      as PCR. Because of no well-defined endemic area and a variable clinical
      presentation as higher thrombocytopenia and nausea associated with Pow infection
      and asymptomatic forms of the pathology with Poc infection, rapid and specific
      identification of Plasmodium ovale curtisi and Plasmodium ovale wallikeri are
      needed. The aim of the study was to evaluate a new quantitative real-time PCR
      coupled with high resolution melting revelation (qPCR-HRM) for identification of
      both species. Results were compared with a nested-PCR, considered as a gold
      standard for Pow and Poc distinction. 356 samples including all human Plasmodium
      species at various parasitaemia were tested. The qPCR-HRM assay allowed Poc and
      Pow discrimination in 66 samples tested with a limit of detection evaluated at 1
      parasite/uL. All these results were concordant with nested-PCR. Cross-reaction
      was absent with others blood parasites. The qPCR-HRM is a rapid and convenient
      technique to Poc and Pow distinction.

PMID- 29321579
TI  - Differentiation potential of Pluripotent Stem Cells correlates to the level of
      CHD7.
AB  - Embryonic Stem Cells (ESC) possesses two distinct features; self-renewal and the
      potential to differentiate. Here we show the differentiation potential and growth
      rate of ESC correlates positively with the expression level of the gene encoding
      chromodomain helicase DNA binding protein 7 (CHD7). When ESCs are maintained in
      feeder-free conditions and single cell seeding, ESC KhES-1 having 4520 copies or
      more of CHD7 in 5 ng total RNA show differentiation potential, but this is lost
      when the CHD7 copy number is reduced in KhES-1 to less than 696 by alternative
      culture conditions. Introduction of siCHD7 reduced differentiation potential and
      growth rate of KhES-1. Interestingly, KhES-1 underwent spontaneous
      differentiation when mCHD7 was introduced and we could not obtain CHD7
      overexpressing ESC in culture. These data suggest that CHD7 drives
      differentiation, and there is a lower limit for CHD7 to initiate differentiation
      and an upper limit for CHD7 if maintained in undifferentiated state, and such
      upper limit varies depending on culture condition. As CHD7 drives cell growth,
      ESC with the highest permissible CHD7 level in the given culture become dominant
      in a couple of passages. Thus, we can select differentiation resistance-free cell
      clones by optimizing the culture system using CHD7 as an index.

PMID- 29321580
TI  - Genome-wide comparative analysis of papain-like cysteine protease family genes in
      castor bean and physic nut.
AB  - Papain-like cysteine proteases (PLCPs) are a class of proteolytic enzymes
      involved in many plant processes. Compared with the extensive research in
      Arabidopsis thaliana, little is known in castor bean (Ricinus communis) and
      physic nut (Jatropha curcas), two Euphorbiaceous plants without any recent whole
      genome duplication. In this study, a total of 26 or 23 PLCP genes were identified
      from the genomes of castor bean and physic nut respectively, which can be divided
      into nine subfamilies based on the phylogenetic analysis: RD21, CEP, XCP, XBCP3,
      THI, SAG12, RD19, ALP and CTB. Although most of them harbor orthologs in
      Arabidopsis, several members in subfamilies RD21, CEP, XBCP3 and SAG12 form new
      groups or subgroups as observed in other species, suggesting specific gene loss
      occurred in Arabidopsis. Recent gene duplicates were also identified in these two
      species, but they are limited to the SAG12 subfamily and were all derived from
      local duplication. Expression profiling revealed diverse patterns of different
      family members over various tissues. Furthermore, the evolution characteristics
      of PLCP genes were also compared and discussed. Our findings provide a useful
      reference to characterize PLCP genes and investigate the family evolution in
      Euphorbiaceae and species beyond.

PMID- 29321581
TI  - A ruthenium-based 5-fluorouracil complex with enhanced cytotoxicity and apoptosis
      induction action in HCT116 cells.
AB  - Combination of multifunctionalities into one compound is a rational strategy in
      medicinal chemical design, and have often been used with metallodrug-based
      compounds. In the present study, we synthesized a novel ruthenium-based 5
      fluorouracil complex [Ru(5-FU)(PPh3)2(bipy)]PF6 (PPh3 = triphenylphosphine; and
      bipy = 2,2'-bipyridine) with enhanced cytotoxicity in different cancer cells, and
      assessed its apoptosis induction action in human colon carcinoma HCT116 cells.
      The complex was characterized by infrared, cyclic voltammetry, molar conductance
      measurements, elemental analysis, NMR experiments and X-ray crystallographic
      analysis. In both 2D and 3D cell culture models, the complex presented
      cytotoxicity to cancer cells more potent than 5-FU. A typical morphology of
      apoptotic cell death, increased internucleosomal DNA fragmentation, without cell
      membrane permeability, loss of the mitochondrial transmembrane potential,
      increased phosphatidylserine externalization and caspase-3 activation were
      observed in complex-treated HCT116 cells. Moreover, the pre-treatment with Z-DEVD
      FMK, a caspase-3 inhibitor, reduced the apoptosis induced by the complex,
      indicating cell death by apoptosis through caspase-dependent and mitochondrial
      intrinsic pathways. The complex failed to induce reactive oxygen species
      production and DNA intercalation. In conclusion, the novel complex displays
      enhanced cytotoxicity to different cancer cells, and is able to induce caspase
      mediated apoptosis in HCT116 cells.

PMID- 29321582
TI  - Serum podocalyxin levels correlate with carotid intima media thickness,
      implicating its role as a novel biomarker for atherosclerosis.
AB  - Podocalyxin is a cell surface sialomucin, which is expressed in not only
      glomerular podocytes but also vascular endothelial cells. Urinary podocalyxin is
      used as a marker for glomerular disease. However, there are no reports describing
      serum podocalyxin (s-Podxl) levels. Therefore, the association between s-Podxl
      levels and clinical parameters were examined with 52 patients. s-Podxl level was
      evaluated using enzyme-linked immunosorbent assay. The median s-Podxl level was
      14.2 ng/dL (interquartile range: 10.8-22.2 ng/dL). There were significant
      correlations (correlation coefficient: r > 0.2) of s-Podxl levels with carotid
      intima media thickness (IMT) (r = 0.30, p = 0.0307). Multiple logistic regression
      analysis showed that s-Podxl levels remained significantly associated with
      carotid IMT > 1 mm (OR: 1.15; 95% CI 1.02-1.31, p = 0.026) after adjustments for
      traditional cardiovascular risk factors such as age, sex, current smoking status,
      hypertension, dyslipidemias, and diabetes. In conclusion, s-Podxl is
      independently associated with carotid IMT and might be used as a novel biomarker
      for cardiovascular disease.

PMID- 29321583
TI  - Allele-specific repression of Sox2 through the long non-coding RNA Sox2ot.
AB  - The transcription factor Sox2 controls the fate of pluripotent stem cells and
      neural stem cells. This gatekeeper function requires well-regulated Sox2 levels.
      We postulated that Sox2 regulation is partially controlled by the Sox2
      overlapping long non-coding RNA (lncRNA) gene Sox2ot. Here we show that the RNA
      levels of Sox2ot and Sox2 are inversely correlated during neural differentiation
      of mouse embryonic stem cells (ESCs). Through allele-specific enhanced
      transcription of Sox2ot in mouse Sox2eGFP knockin ESCs we demonstrate that
      increased Sox2ot transcriptional activity reduces Sox2 RNA levels in an allele
      specific manner. Enhanced Sox2ot transcription, yielding lower Sox2 RNA levels,
      correlates with a decreased chromatin interaction of the upstream regulatory
      sequence of Sox2 and the ESC-specific Sox2 super enhancer. Our study indicates
      that, in addition to previously reported in trans mechanisms, Sox2ot can regulate
      Sox2 by an allele-specific mechanism, in particular during development.

PMID- 29321584
TI  - The critical role of phase difference in theta oscillation between bilateral
      parietal cortices for visuospatial working memory.
AB  - Visual working memory (VWM) refers to people's ability to maintain and manipulate
      visual information on line. Its capacity varies between individuals, and
      neuroimaging studies have suggested a link between one's VWM capacity and theta
      power in the parietal cortex. However, it is unclear how the parietal cortices
      communicate with each other in order to support VWM processing. In two
      experiments we employed transcranial alternate current stimulation (tACS) to use
      frequency-specific (6 Hz) alternating current to modulate theta oscillation
      between the left and right parietal cortex with either in-phase (0 degrees 
      difference, Exp 1), anti-phase (180 degrees  difference, Exp 2), or sham
      sinusoidal current stimulation. In Experiment 1, in-phase theta tACS induced an
      improved VWM performance, but only in low-performers, whereas high-performers
      suffered a marginally-significant VWM impairment. In Experiment 2, anti-phase
      theta tACS did not help the low-performers, but significantly impaired high
      performers' VWM capacity. These results not only provide causal evidence for
      theta oscillation in VWM processing, they also highlight the intricate
      interaction between tACS and individual differences-where the same protocol that
      enhances low-performers' VWM can backfire for the high-performers. We propose
      that signal complexity via coherent timing and phase synchronization within the
      bilateral parietal network is crucial for successful VWM functioning.

PMID- 29321585
TI  - Site-specific randomization of the endogenous genome by a regulatable CRISPR-Cas9
      piggyBac system in human cells.
AB  - Randomized mutagenesis at an endogenous chromosomal locus is a promising approach
      for protein engineering, functional assessment of regulatory elements, and
      modeling genetic variations. In mammalian cells, however, it is challenging to
      perform site-specific single-nucleotide substitution with single-stranded
      oligodeoxynucleotide (ssODN) donor templates due to insufficient homologous
      recombination and the infeasibility of positive selection. Here, we developed a
      DNA transposon based CRISPR-Cas9 regulated transcription and nuclear shuttling
      (CRONUS) system that enables the stable transduction of CRISPR-Cas9/sgRNA in
      broad cell types, but avoids undesired genome cleavage in the absence two
      chemical inducing molecules. Highly efficient single nucleotide alterations
      induced randomization of desired codons (up to 4 codons) at a defined genomic
      locus in various human cell lines, including human iPS cells. Thus, CRONUS
      provides a novel platform for modeling diseases and genetic variations.

PMID- 29321586
TI  - Chemicals released by male sea cucumber mediate aggregation and spawning
      behaviours.
AB  - The importance of chemical communication in reproduction has been demonstrated in
      many marine broadcast spawners. However, little is known about the use of
      chemical communication by echinoderms, the nature of the compounds involved and
      their mechanism(s) of action. Here, the hypothesis that the sea cucumber
      Holothuria arguinensis uses chemical communication for aggregation and spawning
      was tested. Water conditioned by males, but not females, attracted both males and
      females; gonad homogenates and coelomic fluid had no effect on attraction. Male
      spawning water, but not female spawning water, stimulated males and females to
      release their gametes; the spermatozoa alone did not induce spawning. H.
      arguinensis male spawning water also induced spawning in the phylogenetically
      related H. mammata. This indicates that males release pheromones together with
      their gametes that induce spawning in conspecifics and possibly sympatric
      species. Finally, the male pheromone seems to be a mixture with at least one
      labile compound (biological activity is lost after four hours at ambient
      temperature) possibly including phosphatidylcholines. The identification of
      pheromones in sea cucumbers offers a new ecological perspective and may have
      practical applications for their aquaculture.

PMID- 29321588
TI  - An experimental approach for real time mass spectrometric CVD gas phase
      investigations.
AB  - This is a report on the first setup of a recently developed, extremely sensitive
      and very fast 3D quadrupole ion trap mass spectrometer inline in a metalorganic
      vapour phase epitaxy (MOVPE) system. This setup was developed ultimately for the
      decomposition- and the interaction analysis of various established as well as
      novel metalorganic sources for MOVPE deposition of III/V semiconductors. To make
      in-situ gas phase and growth interaction analysis on a new level of sensitivity
      possible without disturbing the MOVPE growth process itself, an optimized
      experimental connection of the mass spectrometer to the MOVPE system is required.
      This work reports on the realization of such an experimental setup and provides
      first proof of concept for decomposition analysis. In addition, a comparison to
      previous studies and gas-phase analysis at MOVPE systems will be given in this
      work.

PMID- 29321587
TI  - Distribution analysis of epertinib in brain metastasis of HER2-positive breast
      cancer by imaging mass spectrometry and prospect for antitumor activity.
AB  - Epertinib (S-222611) is a potent, reversible, and selective tyrosine kinase
      inhibitor of epidermal growth factor receptor (EGFR), human EGFR2 (HER2), and
      human EGFR4. We developed experimental brain metastasis models by
      intraventricular injection (intraventricular injection mouse model; IVM) of HER2
      positive breast cancer (MDA-MB-361-luc-BR2/BR3) or T790M-EGFR-positive lung
      cancer (NCI-H1975-luc) cells. After a single oral administration, epertinib and
      lapatinib concentrations in brain metastatic regions were analyzed by
      quantitative imaging mass spectrometry. In the NCI-H1975 lung cancer IVM, the
      concentration of epertinib in brain metastasis was comparable to that of
      lapatinib. However, in the MDA-MB-361 breast cancer IVM, the concentration of
      epertinib in brain metastasis was >10 times higher than that of lapatinib.
      Furthermore, the epertinib tumor-to-normal brain ratio was ~4 times higher than
      that of lapatinib. Blood-tumor barrier (BTB) permeability was assessed in each
      brain metastatic region. In the lung cancer model, fluorescently labeled dextran
      was more highly detected in brain metastatic regions than in brain parenchyma.
      However, in breast cancer models, dextran fluorescence intensity in brain
      metastatic regions and brain parenchyma were comparable, suggesting that the BTB
      remained largely intact. Epertinib would be promised as a therapeutic agent for
      HER2-positive breast cancer with brain metastasis.

PMID- 29321589
TI  - Comparative analysis of low complexity regions in Plasmodia.
AB  - Low complexity regions (LCRs) are a common feature shared by many genomes, but
      their evolutionary and functional significance remains mostly unknown. At the
      core of the uncertainty is a poor understanding of the mechanisms that regulate
      their retention in genomes, whether driven by natural selection or neutral
      evolution. Applying a comparative approach of LCRs to multiple strains and
      species is a powerful approach to identify patterns of conservation in these
      regions. Using this method, we investigate the evolutionary history of LCRs in
      the genus Plasmodium based on orthologous protein coding genes shared by 11
      species and strains from primate and rodent-infecting pathogens. We find multiple
      lines of evidence in support of natural selection as a major evolutionary force
      shaping the composition and conservation of LCRs through time and signatures that
      their evolutionary paths are species specific. Our findings add a comparative
      analysis perspective to the debate on the evolution of LCRs and harness the power
      of sequence comparisons to identify potential functionally important LCR
      candidates.

PMID- 29321590
TI  - Six domoic acid related compounds from the red alga, Chondria armata, and domoic
      acid biosynthesis by the diatom, Pseudo-nitzschia multiseries.
AB  - Domoic acid (DA, 1), a potent neurotoxin that causes amnesic shellfish poisoning,
      has been found in diatoms and red algae. While biosynthetic pathway towards DA
      from geranyl diphosphate and L-glutamate has been previously proposed, its late
      stage is still unclear. Here, six novel DA related compounds, 7'-methyl-isodomoic
      acid A (2) and B (3), N-geranyl-L-glutamic acid (4), 7'-hydroxymethyl-isodomoic
      acid A (5) and B (6), and N-geranyl-3(R)-hydroxy-L-glutamic acid (7), were
      isolated from the red alga, Chondria armata, and their structures were
      determined. The compounds 4 and 7, linear compounds, are predictable as the
      precursors to form the DA pyrrolidine ring. The compounds 2 and 3 are thought as
      the cyclized products of 7; therefore, dehydration and electron transfer from the
      internal olefin of 7 is a possible mechanism for the pyrrolidine ring formation.
      One terminal methyl group of the side chain of 2 and 3 is predicted to be
      oxidized to hydroxymethyl (5, 6), and then to carboxylic acids, forming isodomoic
      acids A and B. Finally, the terminal olefin of isodomoic acid A would be
      isomerized to form DA. In addition, [15N, D]-labeled 4 was incorporated into DA
      using the diatom, Pseudo-nitzschia multiseries, demonstrating that 4 is the
      genuine precursor of DA.

PMID- 29321593
TI  - Welcome message from the new Editor-in-Chief.

PMID- 29321591
TI  - Respiratory Syncytial Virus Infection Changes Cargo Composition of Exosome
      Released from Airway Epithelial Cells.
AB  - Exosomes are microvesicles known to carry biologically active molecules,
      including RNA, DNA and proteins. Viral infections can induce profound changes in
      exosome composition, and exosomes have been implicated in viral transmission and
      pathogenesis. No information is current available regarding exosome composition
      and function during infection with Respiratory Syncytial Virus (RSV), the most
      important cause of lower respiratory tract infections in children. In this study,
      we characterized exosomes released from RSV-infected lung carcinoma-derived A549
      cells. RNA deep sequencing revealed that RSV exosomes contain a diverse range of
      RNA species like messenger and ribosomal RNA fragments, as well as small
      noncoding RNAs, in a proportion different from exosomes isolated from mock
      infected cells. We observed that both RNA and protein signatures of RSV were
      present in exosomes, however, they were not able to establish productive
      infection in uninfected cells. Exosomes isolated from RSV-infected cells were
      able to activate innate immune response by inducing cytokine and chemokine
      release from human monocytes and airway epithelial cells. These data suggest that
      exosomes may play an important role in pathogenesis or protection against
      disease, therefore understating their role in RSV infection may open new avenues
      for target identification and development of novel therapeutics.

PMID- 29321592
TI  - Amyloid beta causes excitation/inhibition imbalance through dopamine receptor 1
      dependent disruption of fast-spiking GABAergic input in anterior cingulate
      cortex.
AB  - Alzheimer's disease (AD) is the most common cause of dementia in the elderly. At
      the early stages of AD development, the soluble beta-amyloid (Abeta) induces
      synaptic dysfunction, perturbs the excitation/inhibition balance of neural
      circuitries, and in turn alters the normal neural network activity leading to
      cognitive decline, but the underlying mechanisms are not well established. Here
      by using whole-cell recordings in acute mouse brain slices, we found that 50 nM
      Abeta induces hyperexcitability of excitatory pyramidal cells in the cingulate
      cortex, one of the most vulnerable areas in AD, via depressing inhibitory
      synaptic transmission. Furthermore, by simultaneously recording multiple cells,
      we discovered that the inhibitory innervation of pyramidal cells from fast
      spiking (FS) interneurons instead of non-FS interneurons is dramatically
      disrupted by Abeta, and perturbation of the presynaptic inhibitory
      neurotransmitter gamma-aminobutyric acid (GABA) release underlies this inhibitory
      input disruption. Finally, we identified the increased dopamine action on
      dopamine D1 receptor of FS interneurons as a key pathological factor that
      contributes to GABAergic input perturbation and excitation/inhibition imbalance
      caused by Abeta. Thus, we conclude that the dopamine receptor 1-dependent
      disruption of FS GABAergic inhibitory input plays a critical role in Abeta
      induced excitation/inhibition imbalance in anterior cingulate cortex.

PMID- 29321594
TI  - Estimating the capacity for production of formamide by radioactive minerals on
      the prebiotic Earth.
AB  - Water creates special problems for prebiotic chemistry, as it is
      thermodynamically favorable for amide and phosphodiester bonds to hydrolyze. The
      availability of alternative solvents with more favorable properties for the
      formation of prebiotic molecules on the early Earth may have helped bypass this
      so-called "water paradox". Formamide (FA) is one such solvent, and can serve as a
      nucleobase precursor, but it is difficult to envision how FA could have been
      generated in large quantities or accumulated in terrestrial surface environments.
      We report here the conversion of aqueous acetonitrile (ACN) via hydrogen cyanide
      (HCN) as an intermediate into FA by gamma-irradiation under conditions mimicking
      exposure to radioactive minerals. We estimate that a radioactive placer deposit
      could produce 0.1-0.8 mol FA km-2 year-1. A uraninite fission zone comparable to
      the Oklo reactors in Gabon can produce 0.1-1 mol m-2 year-1, orders of magnitude
      greater than other scenarios of FA production or delivery for which reaching
      sizeable concentrations of FA are problematic. Radioactive mineral deposits may
      be favorable settings for prebiotic compound formation through emergent geologic
      processes and FA-mediated organic chemistry.

PMID- 29321597
TI  - Microbial habitability of Europa sustained by radioactive sources.
AB  - There is an increasing interest in the icy moons of the Solar System due to their
      potential habitability and as targets for future exploratory missions, which
      include astrobiological goals. Several studies have reported new results
      describing the details of these moons' geological settings; however, there is
      still a lack of information regarding the deep subsurface environment of the
      moons. The purpose of this article is to evaluate the microbial habitability of
      Europa constrained by terrestrial analogue environments and sustained by
      radioactive energy provided by natural unstable isotopes. The geological
      scenarios are based on known deep environments on Earth, and the bacterial
      ecosystem is based on a sulfate-reducing bacterial ecosystem found 2.8 km below
      the surface in a basin in South Africa. The results show the possibility of
      maintaining the modeled ecosystem based on the proposed scenarios and provides
      directions for future models and exploration missions for a more complete
      evaluation of the habitability of Europa and of icy moons in general.

PMID- 29321595
TI  - MicroRNA-7 mediates cross-talk between metabolic signaling pathways in the liver.
AB  - MicroRNAs (miRNAs) have emerged as critical regulators of cellular metabolism. To
      characterise miRNAs crucial to the maintenance of hepatic lipid homeostasis, we
      examined the overlap between the miRNA signature associated with inhibition of
      peroxisome proliferator activated receptor-alpha (PPAR-alpha) signaling, a
      pathway regulating fatty acid metabolism, and the miRNA profile associated with
      25-hydroxycholesterol treatment, an oxysterol regulator of sterol regulatory
      element binding protein (SREBP) and liver X receptor (LXR) signaling. Using this
      strategy, we identified microRNA-7 (miR-7) as a PPAR-alpha regulated miRNA, which
      activates SREBP signaling and promotes hepatocellular lipid accumulation. This is
      mediated, in part, by suppression of the negative regulator of SREBP signaling:
      ERLIN2. miR-7 also regulates genes associated with PPAR signaling and sterol
      metabolism, including liver X receptor beta (LXR-beta), a transcriptional
      regulator of sterol synthesis, efflux, and excretion. Collectively, our findings
      highlight miR-7 as a novel mediator of cross-talk between PPAR, SREBP, and LXR
      signaling pathways in the liver.

PMID- 29321598
TI  - A new macrofaunal limit in the deep biosphere revealed by extreme burrow depths
      in ancient sediments.
AB  - Macrofauna is known to inhabit the top few 10s cm of marine sediments, with rare
      burrows up to two metres below the seabed. Here, we provide evidence from deep
      water Permian strata for a previously unrecognised habitat up to at least 8
      metres below the sediment-water interface. Infaunal organisms exploited networks
      of forcibly injected sand below the seabed, forming living traces and reworking
      sediment. This is the first record that shows sediment injections are responsible
      for hosting macrofaunal life metres below the contemporaneous seabed. In
      addition, given the widespread occurrence of thick sandy successions that
      accumulate in deep-water settings, macrofauna living in the deep biosphere are
      likely much more prevalent than considered previously. These findings should
      influence future sampling strategies to better constrain the depth range of
      infaunal animals living in modern deep-sea sands. One Sentence Summary: The
      living depth of infaunal macrofauna is shown to reach at least 8 metres in new
      habitats associated with sand injections.

PMID- 29321596
TI  - High Resolution 31P NMR Spectroscopy Generates a Quantitative Evolution Profile
      of Phosphorous Translocation in Germinating Sesame Seed.
AB  - Phosphorus metabolism and circulation are essential bio-physicochemical processes
      during development of a plant and have been extensively studied and known to be
      affected by temperature, humidity, lighting, hormones etc. However, a
      quantitative description of how various phosphorous species evolve over time has
      not been reported. In this work, a combined 31P liquid and solid state NMR
      spectroscopic methodology is employed, supported by a new extraction scheme and
      data analysis method, to carry out a quantitative investigation of phosphorous
      circulation in germinating sesame seeds in dark and under illumination with and
      without adding a growth hormone. The spectra show that only slight changes occur
      for phosphorous metabolism at the initial stage but a rapid change takes place
      between 48-96 hours after germination is started. The metabolism is found to be
      temperature dependent and affected by illumination and hormone. However, neither
      illumination nor hormone affects the final residual concentration of phytin.
      Moreover, phytin does not flow out of cotyledon and the phosphorous flowing to
      other parts of the plant is always in the inorganic form. The overall evolution
      profile of phytate consumption is found to be a Gaussian decaying function. These
      findings can be explained with a dynamic model on phytin conversion.

PMID- 29321599
TI  - Splicing QTL of human adipose-related traits.
AB  - Recently, genome-wide association studies (GWAS) have identified 11 loci
      associated with adipose-related traits across different populations. However,
      their functional roles still remain largely unknown. In this study, we aimed to
      explore the splicing regulation of these GWAS signals in a tissue-specific
      fashion. For adipose-related GWAS signals, we selected six adipose-related
      tissues (adipose subcutaneous, artery tibial, blood, heart left ventricle, muscle
      skeletal, and thyroid) with the sample size greater than 80 for splicing
      quantitative trait loci (QTL) analysis using GTEx released datasets. We
      integrated GWAS summary statistics of nine adipose-related traits (an average of
      2.6 million SNPs per GWAS), and splicing QTLs from 6 GTEx tissues with an average
      of 337,900 splicing QTL SNPs, and 684,859 junctions. Our filtering process
      generated an average of 86,549 SNPs and 162,841 exon-exon links (junctions) for
      each tissue. A total of seven exon-exon junctions in four genes (AKTIP, DTNBP1,
      FTO and UBE2E1) were found to be significantly associated with four SNPs that
      showed genome-wide significance with body fat distribution (rs17817288,
      rs7206790, rs11710420 and rs2237199). These splicing events might contribute to
      the causal effect on the regulation of ectopic-fat, which warrants further
      experimental validation.

PMID- 29321600
TI  - Fis is a global regulator critical for modulation of virulence factor production
      and pathogenicity of Dickeya zeae.
AB  - Dickeya zeae is the causal agent of rice foot rot disease, which has recently
      become a great threat to rice planting countries and regions. The pathogen
      produces a family of phytotoxins named zeamines that is critical for bacterial
      virulence, but little is known about the signaling pathways and regulatory
      mechanisms that govern zeamine production. In this study, we showed that a
      conserved transcriptional regulator Fis is involved in the regulation of zeamine
      production in D. zeae strain EC1. Deletion mutants were markedly attenuated in
      the virulence against rice seed germination. Transcriptome and phenotype analyses
      showed that Fis is a potent global transcriptional regulator modulating various
      virulence traits, including production of extracellular enzymes and
      exopolysaccharides, swimming and swarming motility, biofilm formation and cell
      aggregation. DNA gel retardation analysis showed that Fis directly regulates the
      transcription of key virulence genes and the genes encoding Vfm quorum sensing
      system through DNA/protein interaction. Our findings unveil a key regulator
      associated with the virulence of D. zeae EC1, and present useful clues for
      further elucidation of the regulatory complex and signaling pathways which govern
      the virulence of this important pathogen.

PMID- 29321601
TI  - CRISPR/Cas9-mediated gene modification and gene knock out in the human-infective
      parasite Trichomonas vaginalis.
AB  - The sexually-transmitted parasite Trichomonas vaginalis infects ~1/4 billion
      people worldwide. Despite its prevalence and myriad adverse outcomes of
      infection, the mechanisms underlying T. vaginalis pathogenesis are poorly
      understood. Genetic manipulation of this single-celled eukaryote has been
      hindered by challenges presented by its complex, repetitive genome and
      inefficient methods for introducing DNA (i.e. transfection) into the parasite.
      Here, we have developed methods to increase transfection efficiency using
      nucleofection, with the goal of efficiently introducing multiple DNA elements
      into a single T. vaginalis cell. We then created DNA constructs required to
      express several components essential to drive CRISPR/Cas9-mediated DNA
      modification: guide RNA (gRNA), the Cas9 endonuclease, short oligonucleotides and
      large, linearized DNA templates. Using these technical advances, we have
      established CRISPR/Cas9-mediated repair of mutations in genes contained on
      circular DNA plasmids harbored by the parasite. We also engineered CRISPR/Cas9
      directed homologous recombination to delete (i.e. knock out) two non-essential
      genes within the T. vaginalis genome. This first report of the use of the
      CRISPR/Cas9 system in T. vaginalis greatly expands the ability to manipulate the
      genome of this pathogen and sets the stage for testing of the role of specific
      genes in many biological processes.

PMID- 29321602
TI  - Multifunctional microfluidic chip for optical nanoprobe based RNA detection -
      application to Chronic Myeloid Leukemia.
AB  - Many diseases have their treatment options narrowed and end up being fatal if
      detected during later stages. As a consequence, point-of-care devices have an
      increasing importance for routine screening applications in the health sector due
      to their portability, fast analyses and decreased cost. For that purpose, a
      multifunctional chip was developed and tested using gold nanoprobes to perform
      RNA optical detection inside a microfluidic chip without the need of molecular
      amplification steps. As a proof-of-concept, this device was used for the rapid
      detection of chronic myeloid leukemia, a hemato-oncological disease that would
      benefit from early stage diagnostics and screening tests. The chip passively
      mixed target RNA from samples, gold nanoprobes and saline solution to infer a
      result from their final colorimetric properties. An optical fiber network was
      used to evaluate its transmitted spectra inside the chip. Trials provided
      accurate output results within 3 min, yielding signal-to-noise ratios up to 9 dB.
      When compared to actual state-of-art screening techniques of chronic myeloid
      leukemia, these results were, at microscale, at least 10 times faster than the
      reported detection methods for chronic myeloid leukemia. Concerning point-of-care
      applications, this work paves the way for other new and more complex versions of
      optical based genosensors.

PMID- 29321603
TI  - Plasma adiponectin levels and type 2 diabetes risk: a nested case-control study
      in a Chinese population and an updated meta-analysis.
AB  - Results from previous prospective studies assessing the relation between
      adiponectin and type 2 diabetes (T2D) were not entirely consistent, and evidence
      in Chinese population is scarce. Moreover, the last meta-analysis did not examine
      the impact of metabolic variables on the adiponectin-T2D association. Therefore,
      we prospectively evaluated the adiponectin-T2D association among 571 T2D cases
      and 571 age-sex-matched controls nested within the Singapore Chinese Health Study
      (SCHS). Furthermore, we conducted an updated meta-analysis by searching
      prospective studies on Pubmed till September 2016. In the SCHS, the odds ratio of
      T2D, comparing the highest versus lowest tertile of adiponectin levels, was 0.30
      (95% confidence interval: 0.17, 0.55) in the fully-adjusted model. The relation
      was stronger among heavier participants (body mass index >=23 kg/m2) compared to
      their leaner counterparts (P for interaction = 0.041). In a meta-analysis of 34
      prospective studies, the pooled relative risk was 0.53 (95% confidence interval:
      0.47, 0.61) comparing the extreme tertiles of adiponectin with moderate
      heterogeneity (I 2 = 48.7%, P = 0.001). The adiponectin-T2D association remained
      unchanged after adjusting for inflammation and dyslipidemia markers, but
      substantially attenuated with adjustment for insulin sensitivity and/or glycaemia
      markers. Overall evidence indicates that higher adiponectin levels are associated
      with decreased T2D risk in Chinese and other populations.

PMID- 29321604
TI  - Trophic transfer and individual impact of nano-sized polystyrene in a four
      species freshwater food chain.
AB  - This study investigated the trophic transfer, individual impact, and embryonic
      uptake of fluorescent nano-sized polystyrene plastics (nanoplastics) through
      direct exposure in a freshwater ecosystem, with a food chain containing four
      species. The alga Chlamydomonas reinhardtii, water flea Daphnia magna, secondary
      consumer fish Oryzias sinensis, and end-consumer fish Zacco temminckii were used
      as test species. In the trophic transfer test, algae were exposed to 50 mg/L
      nanoplastics, defined as plastic particles <100 nm in diameter; higher trophic
      level organisms were exposed through their diet. In the direct exposure test,
      each species was directly exposed to nanoplastics. Microscopic analysis confirmed
      that the nanoplastics adhered to the surface of the primary producer and were
      present in the digestive organs of the higher trophic level species. Nanoplastics
      also negatively affected fish activity, as measured by distance traveled and area
      covered, and induced histopathological changes in the livers of fish that were
      directly exposed. Additionally, nanoplastics penetrated the embryo walls and were
      present in the yolk sac of hatched juveniles. These observations clearly show
      that nanoplastics are easily transferred through food chain, albeit because of
      high experimental dosages. Nevertheless, the results strongly point to the
      potential health risks of nanoplastic exposure.

PMID- 29321606
TI  - Reevaluation of the Dentary Structures of Caenagnathid Oviraptorosaurs
      (Dinosauria, Theropoda).
AB  - Among the characters of caenagnathid oviraptorosaurians, the lateral occlusal
      grooves and ridges on the occlusal surface of the jaw bones often receive special
      attention. Recent studies demonstrated that ontogenetic edentulism is present in
      caenagnathids, and therefore the lateral occlusal grooves and ridges are
      vestigial alveoli and interdental septa, respectively. In the present paper, the
      dentary structures of caenagnathids were reevaluated based on CT images of
      Caenagnathiasia sp. IVPP V20377. Several previously unknown features including
      crateriform vestigial alveoli, the morphology of the dentary interior hollow
      space, and the paired blind tubes beneath the dentary symphyseal shelf are
      recognized. Current lines of evidence suggest different jaw bone morphologies are
      likely produced by various tooth reduction patterns, which indicates ontogenetic
      dietary shift, if once presented in caenagnathids and Sapeornis, may have been
      different from the condition seen in Limusaurus. The 3D images of dentary
      interior spaces suggest that while tooth reduction progresses, the empty alveoli
      are partially modified into structures accommodating blood vessels that nourish
      the rhamphotheca, probably representing a functional compensation for the
      insufficient blood supply in toothed jaw bones.

PMID- 29321605
TI  - Trends and Patterns of Cancer Mortality in North China (Hebei Province), 1973
      2013.
AB  - Little was known about the cancer burden for the last 40 years in middle-income
      province in China. This study aimed to assess the overall, cause-specific
      mortality cancer trend and disability-adjusted life years (DALYs) between 1973
      1975 and 2011-2013 in North China (Hebei Province). The collected data were
      stratified by 5-year age groups, gender and different types of cancer. We found
      that mortality from cancer showed an upward trend in the 1973-2013. The mortality
      rate of 0-79 year-old in 2011-2013 was lower than that in other periods. It was
      about two times higher for the 80+ age group than it was in 1973-1975. The cancer
      pattern in 4 periods presented differently. Esophagus cancer ranked the first in
      1973-1975, whereas in 2011-2013, the most common cancer was lung cancer. DALYs
      also showed an increasing cancer burden in Hebei Province. This study is the
      first to analyze cancer burden for the last 40 years in a middle-income province.
      It could provide a baseline for assessment of effectiveness of cancer prevention
      and control. Esophagus cancer had a significant declining trend because of
      endoscopy screening program. Enhancing screening programs in those aged 40-69
      year-old is necessary for reducing the cancer burden.

PMID- 29321607
TI  - Responses in shoot elongation, carbohydrate utilization and growth recovery of an
      invasive species to submergence at different water temperatures.
AB  - Widely distributed amphibious exotic plant species may respond plastically to
      water temperatures when submerged. Alternanthera philoxeroides, a highly flood
      tolerant species, originates from tropical regions and has successfully invaded
      temperate regions. The wide distribution of this species suggests it can respond
      to flooding at different water temperatures. In this study, the plastic responses
      of A. philoxeroides plants to submergence at water temperatures of 10  degrees C,
      20  degrees C and 30  degrees C were investigated. The A. philoxeroides plants
      had large pools of non-structural carbohydrates, which were readily mobilized
      upon submergence. Submergence hindered biomass accumulation and decreased the
      carbohydrate content level and respiration rate (P < 0.05). Water temperature had
      remarkable effects on shoot elongation, carbohydrate utilization and recovery
      growth. With decreasing water temperature, the respiration rate was lower and
      carbohydrate content decreased more slowly, but the post-submergence biomass
      accumulation was faster (P < 0.05), indicating a beneficial effect of low water
      temperature for recovery. However, high water temperatures accelerated shoot
      elongation (P < 0.05), which benefitted the submerged plants more if contact with
      air was restored. These results suggest that the species can respond to different
      water temperatures plastically, which may provide hints for its invasion success
      in regions with diverse climates.

PMID- 29321608
TI  - The effect of maternal vitamin D deficiency during pregnancy on body fat and
      adipogenesis in rat offspring.
AB  - To evaluate the effects of maternal vitamin D deficiency on body fat and
      adipogenesis in offspring rats, and explore the potential mechanism, we
      constructed a vitamin D deficient rat model and performed metabolic activity
      evaluation, body fat monitoring, biochemical analysis, adipogenesis assay,
      methylation microarray and RNA-seq for their offspring rats. We found the weight
      of vitamin D deficient (VDD) offspring was gradually higher than that of control
      (CLT) offspring, and the difference was significant since 10 weeks old. When
      compared with CTL offspring, the 24 h heat production, peak blood glucose,
      adipose tissue volume and blood lipid indexes were significantly increased in VDD
      offspring at 14 weeks old. Moreover, a significant increase in proliferation rate
      and number of lipid droplets for pre-adipocytes was also observed in VDD
      offspring group. DNA methylation profiling showed that compared to CTL group, 608
      promoters and 204 CpG islands were differentially methylated in the VDD group,
      involving 305 genes. When combined with the results of RNA-seq, 141 genes of the
      methylated genes were differentially expressed. In conclusion, vitamin D
      deficiency during pregnancy may promote the proliferation and differentiation of
      pre-adipocytes, which may be associated with methylation alterations of genes,
      ultimately leading to offspring obesity.

PMID- 29321609
TI  - Complex Formation via Hydrogen bonding between Rhodamine B and Montmorillonite in
      Aqueous Solution.
AB  - This study investigates the adsorption mechanism differences among four
      nitrogenous dyes, sulforhodamine G (SRG), uncharged/deprotonated rhodamine B
      (RhB), orange II (Or II) and methyl blue (MB) by montmorillonite (MMT). MMT
      adsorption capacity for cationic MB was three times that of uncharged RhB and
      anionic SRG, while anionic Or II was not absorbed. Colloidal MMT particles have
      two types of surfaces, basal and edge, that interact with nitrogenous dyes very
      differently. The surface acidity of MMT was characterized with the pyridine
      adsorption method using in-situ diffuse reflectance infrared Fourier transform
      spectroscopy (in-situ DRIFTS). Adsorption of cationic MB was compared with the
      adsorption of RhB. In-situ attenuated total reflectance Fourier transform
      infrared (in-situ ATR-FTIR) spectroscopy indicated that a nitrogen atom on RhB
      complexes with a metal hydroxyl on an MMT edge through a water bridge. The highly
      polar edge hydroxyl is important to hydrogen bond formation. Cation ion exchange
      and washing experiments, as well as studies on the effect of temperature, pH and
      ionic strength on adsorption further clarified the adsorption mechanism. Our
      results provide insights into the effects of molecular structure on the
      adsorption of nitrogenous dyes by clay and the role of edge surfaces in the
      adsorption process.

PMID- 29321610
TI  - Physiological effects of short acute UVB treatments in Chenopodium quinoa Willd.
AB  - Increased ultraviolet B (UVB) radiation due to global change can affect plant
      growth and metabolism. Here, we evaluated the capacity of quinoa to resist under
      short acute UVB irradiation. Quinoa was daily exposed for 30 or 60 min to 1.69 W
      m-2 UVB. The results showed that 30 min exposure in 9 d-course did not cause
      severe alterations on photosynthetic pigments and flavonoids, but a significant
      increase of antioxidant capacity was observed. Otherwise, 60 min UVB in 5 d
      course reduced almost all these parameters except for an increase in the de
      epoxidation of xanthophyll cycle pigments and led to the death of the plants.
      Further studies of gas exchange and fluorescence measurements showed that 30 min
      UVB dramatically decrease stomatal conductance, probably associated to reactive
      oxygen species (ROS) production. Inhibition of photosynthetic electron transport
      was also observed, which could be a response to reduce ROS. Otherwise,
      irreversible damage to the photosynthetic apparatus was found with 60 min UVB
      probably due to severe ROS overproduction that decompensates the redox balance
      inducing UVB non-specific signaling. Moreover, 60 min UVB compromised Rubisco
      carboxylase activity and photosynthetic electron transport. Overall, these data
      suggest that quinoa modulates different response mechanisms depending on the UVB
      irradiation dosage.

PMID- 29321611
TI  - Acetaldehyde inhibits retinoic acid biosynthesis to mediate alcohol
      teratogenicity.
AB  - Alcohol consumption during pregnancy induces Fetal Alcohol Spectrum Disorder
      (FASD), which has been proposed to arise from competitive inhibition of retinoic
      acid (RA) biosynthesis. We provide biochemical and developmental evidence
      identifying acetaldehyde as responsible for this inhibition. In the embryo, RA
      production by RALDH2 (ALDH1A2), the main retinaldehyde dehydrogenase expressed at
      that stage, is inhibited by ethanol exposure. Pharmacological inhibition of the
      embryonic alcohol dehydrogenase activity, prevents the oxidation of ethanol to
      acetaldehyde that in turn functions as a RALDH2 inhibitor. Acetaldehyde-mediated
      reduction of RA can be rescued by RALDH2 or retinaldehyde supplementation.
      Enzymatic kinetic analysis of human RALDH2 shows a preference for acetaldehyde as
      a substrate over retinaldehyde. RA production by hRALDH2 is efficiently inhibited
      by acetaldehyde but not by ethanol itself. We conclude that acetaldehyde is the
      teratogenic derivative of ethanol responsible for the reduction in RA signaling
      and induction of the developmental malformations characteristic of FASD. This
      competitive mechanism will affect tissues requiring RA signaling when exposed to
      ethanol throughout life.

PMID- 29321612
TI  - Blimp-1/PRDM1 is a critical regulator of Type III Interferon responses in mammary
      epithelial cells.
AB  - The transcriptional repressor Blimp-1 originally cloned as a silencer of type I
      interferon (IFN)-beta gene expression controls cell fate decisions in multiple
      tissue contexts. Conditional inactivation in the mammary gland was recently shown
      to disrupt epithelial cell architecture. Here we report that Blimp-1 regulates
      expression of viral defense, IFN signaling and MHC class I pathways, and directly
      targets the transcriptional activator Stat1. Blimp-1 functional loss in 3D
      cultures of mammary epithelial cells (MECs) results in accumulation of dsRNA and
      expression of type III IFN-lambda. Cultures treated with IFN lambda similarly
      display defective lumen formation. These results demonstrate that type III IFN
      lambda profoundly influences the behavior of MECs and identify Blimp-1 as a
      critical regulator of IFN signaling cascades.

PMID- 29321613
TI  - Evaluation of in vivo digital root reconstruction based on anatomical
      characteristics of the periodontal ligament using cone beam computed tomography.
AB  - This study's aim was to develop and validate an approach to automatically extract
      and reconstruct three-dimensional (3D) digital root models from in vivo teeth
      based on the anatomical characteristics of the periodontal ligament using cone
      beam computed tomography (CBCT) data. Prior to undergoing dental extractions for
      orthodontic purposes, the CBCT data of each study participant were collected and
      imported into Mimics software to reconstruct 3D in vivo digital root models (test
      models). Twenty roots of 17 teeth extracted from the study's participants were
      scanned using a dental scanner to obtain 3D in vitro digital root models
      (reference models). The 3D morphological deviation between the reference and test
      models was compared; the 3D size of the bucco-lingual, mesio-distal, and root
      length dimensions were calculated. This approach achieved an average 3D
      morphological deviation of 0.21 mm, and the average size error in the bucco
      lingual, mesio-distal, and root length dimensions were -0.35 mm, -0.17 mm, and
      0.47 mm, respectively. This new automatic extraction approach rapidly and
      accurately reconstructs 3D in vivo root models with detailed morphological
      information, and has the potential to improve diagnostic and treatment work flow
      in orthodontic clinics, as well as in other areas of dentistry.

PMID- 29321614
TI  - Effects on metabolic parameters in young rats born with low birth weight after
      exposure to a mixture of pesticides.
AB  - Pesticide exposure during fetal life can lead to low birth weight and is commonly
      observed in reproductive toxicology studies. Associations have also been found in
      low birth weight babies born from pesticide-exposed gardeners. Since low birth
      weight is also linked to metabolic disorders, it can be speculated that early
      life exposure to pesticides could increase the risk of becoming obese or
      developing diabetes later in life. We have analyzed potential long-term effects
      of gestational and lactational exposure to a low dose mixture of six pesticides
      that individually can cause low birth weight: Cyromazine, MCPB, Pirimicarb,
      Quinoclamine, Thiram, and Ziram. Exposed male offspring, who were smaller than
      controls, displayed some degree of catch-up growth. Insulin and glucagon
      regulation was not significantly affected, and analyses of liver and pancreas did
      not reveal obvious histopathological effects. Efforts towards identifying
      potential biomarkers of metabolic disease-risk did not result in any strong
      candidates, albeit leptin levels were altered in exposed animals. In fat tissues,
      the key genes Lep, Nmb and Nmbr were altered in high dosed offspring, and were
      differentially expressed between sexes. Our results suggest that early-life
      exposure to pesticides may contribute to the development of metabolic disorders
      later in life.

PMID- 29321616
TI  - Defocus and magnification dependent variation of TEM image astigmatism.
AB  - Daily alignment of the microscope is a prerequisite to reaching optimal lens
      conditions for high resolution imaging in cryo-EM. In this study, we have
      investigated how image astigmatism varies with the imaging conditions (e.g.
      defocus, magnification). We have found that the large change of
      defocus/magnification between visual correction of astigmatism and subsequent
      data collection tasks, or during data collection, will inevitably result in
      undesirable astigmatism in the final images. The dependence of astigmatism on the
      imaging conditions varies significantly from time to time, so that it cannot be
      reliably compensated by pre-calibration of the microscope. Based on these
      findings, we recommend that the same magnification and the median defocus of the
      intended defocus range for final data collection are used in the objective lens
      astigmatism correction task during microscope alignment and in the focus mode of
      the iterative low-dose imaging. It is also desirable to develop a fast, accurate
      method that can perform dynamic correction of the astigmatism for different
      intended defocuses during automated imaging. Our findings also suggest that the
      slope of astigmatism changes caused by varying defocuses can be used as a
      convenient measurement of objective lens rotation symmetry and potentially an
      acceptance test of new electron microscopes.

PMID- 29321617
TI  - Alleviation of drought stress in Phyllostachys edulis by N and P application.
AB  - The aim of this study was to explore whether nutrition supply can improve the
      drought tolerance of Moso bamboo under dry conditions. One-year-old seedlings
      were exposed to two soil water content levels [wellwatered, 70 +/- 5% soil
      relative-water-content (SRWC) and drought stress, 30 +/- 5% SRWC] and four
      combinations of nitrogen (N) and phosphorus (P) supply (low-N, low-P, LNLP; low
      N, high-P, LNHP; high-N, high-P, HNHP; and high-N, low-P, HNLP) for four months.
      Plant growth, photosynthesis, chlorophyll fluorescence, water use efficiency and
      cell membrane stability were determined. The results showed that drought stress
      significantly decreased total biomass, net-photosynthesis (Pn), stomatal
      conductance (gs), leaf-chlorophyll-content (Chlleaf), PSII-quantum-yield
      (PhiPSII), maximum-quantum-yield-of-photosynthesis (Fv/Fm), photochemical
      quenching-coefficient (qP), leaf-instantaneous-water-use efficiency (WUEi),
      relative-water-content (RWC), photosynthetic-N-use-efficiency (PNUE), and
      photosynthetic-P-use-efficiency (PPUE). N and P application was found to be
      effective in enhancing the concentration of leaf N, gs, and Pn while reducing the
      production of reactive oxygen species under both water regimes. Under LNHP, HNHP
      and HNLP treatments, the decreases in total biomass, Pn, Chlleaf and Fv/Fm of
      drought-stressed were less evident than the decreases under LNLP. The study
      suggests that nutrient application has the potential to mitigate the drastic
      effects of water stress on Moso bamboo by improving photosynthetic rate, water
      use efficiency, and increasing of membrane integrity.

PMID- 29321615
TI  - Functional Isolation of Tumor-Initiating Cells using Microfluidic-Based Migration
      Identifies Phosphatidylserine Decarboxylase as a Key Regulator.
AB  - Isolation of tumor-initiating cells currently relies on markers that do not
      reflect essential biologic functions of these cells. We proposed to overcome this
      limitation by isolating tumor-initiating cells based on enhanced migration, a
      function tightly linked to tumor-initiating potential through epithelial-to
      mesenchymal transition (EMT). We developed a high-throughput microfluidic
      migration platform with automated cell tracking software and facile recovery of
      cells for downstream functional and genetic analyses. Using this device, we
      isolated a small subpopulation of migratory cells with significantly greater
      tumor formation and metastasis in mouse models. Whole transcriptome sequencing of
      migratory versus non-migratory cells from two metastatic breast cancer cell lines
      revealed a unique set of genes as key regulators of tumor-initiating cells. We
      focused on phosphatidylserine decarboxylase (PISD), a gene downregulated by 8
      fold in migratory cells. Breast cancer cells overexpressing PISD exhibited
      reduced tumor-initiating potential in a high-throughput microfluidic mammosphere
      device and mouse xenograft model. PISD regulated multiple aspects of
      mitochondria, highlighting mitochondrial functions as therapeutic targets against
      cancer stem cells. This research establishes not only a novel microfluidic
      technology for functional isolation of tumor-initiating cells regardless of
      cancer type, but also a new approach to identify essential regulators of these
      cells as targets for drug development.

PMID- 29321618
TI  - Uncoupled mitochondria quickly shorten along their long axis to form indented
      spheroids, instead of rings, in a fission-independent manner.
AB  - Loss of mitochondrial membrane potential (DeltaPsim) triggers dramatic structural
      changes in mitochondria from a tubular to globular shape, referred to as
      mitochondrial fragmentation; the resulting globular mitochondria are called
      swelled or ring/doughnut mitochondria. We evaluated the early period of
      structural changes during the DeltaPsim loss-induced transformation after
      carbonyl cyanide m-chlorophenyl hydrazine (CCCP) administration using a newly
      developed correlative microscopic method combined with fluorescence microscopic
      live imaging and volume electron microscopy. We found that most mitochondria
      changed from a tubular shape to a globular shape without fusion or fission and
      typically showed ring shapes within 10 min after CCCP exposure. In contrast, most
      ring mitochondria did not have a true through hole; rather, they had various
      indents, and 47% showed stomatocyte shapes with vase-shaped cavities, which is
      the most stable physical structure without any structural support if the long
      tubular shape shortens into a sphere. Our results suggested that loss of
      DeltaPsim triggered collapse of mitochondrial structural support mechanisms.

PMID- 29321619
TI  - Ultraviolet-B enhances the resistance of multiple plant species to lepidopteran
      insect herbivory through the jasmonic acid pathway.
AB  - Land plants protect themselves from ultraviolet-B (UV-B) by accumulating UV
      absorbing metabolites, which may also function as anti-insect toxins. Previous
      studies have shown that UV-B enhances the resistance of different plant species
      to pierce-sucking pests; however, whether and how UV-B influences plant defense
      against chewing caterpillars are not well understood. Here we show that UV-B
      treatment increased Spodoptera litura herbivory-induced jasmonic acid (JA)
      production in Arabidopsis and thereby Arabidopsis exhibited elevated resistance
      to S. litura. Using mutants impaired in the biosynthesis of JA and the defensive
      metabolites glucosinolates (GSs), we show that the UV-B-induced resistance to S.
      litura is dependent on the JA-regulated GSs and an unidentified anti-insect
      metabolite(s). Similarly, UV-B treatment also enhanced the levels of JA
      isoleucine conjugate and defense-related secondary metabolites in tobacco, rice,
      and maize after these plants were treated with simulated herbivory of
      lepidopteran insects; consistently, these plants showed elevated resistance to
      insect larvae. Using transgenic plants impaired in JA biosynthesis or signaling,
      we further demonstrate that the UV-B-enhanced defense responses also require the
      JA pathway in tobacco and rice. Our findings reveal a likely conserved JA
      dependent mechanism by which UV-B enhances plant defense against lepidopteran
      insects.

PMID- 29321620
TI  - Lack of PINK1 alters glia innate immune responses and enhances inflammation
      induced, nitric oxide-mediated neuron death.
AB  - Neuroinflammation is involved in the pathogenesis of Parkinson's disease (PD) and
      other neurodegenerative disorders. We show that lack of PINK1- a mitochondrial
      kinase linked to recessive familial PD - leads to glia type-specific
      abnormalities of innate immunity. PINK1 loss enhances LPS/IFN-gamma stimulated
      pro-inflammatory phenotypes of mixed astrocytes/microglia (increased iNOS, nitric
      oxide and COX-2, reduced IL-10) and pure astrocytes (increased iNOS, nitric
      oxide, TNF-alpha and IL-1beta), while attenuating expression of both pro
      inflammatory (TNF-alpha, IL-1beta) and anti-inflammatory (IL-10) cytokines in
      microglia. These abnormalities are associated with increased inflammation-induced
      NF-kappaB signaling in astrocytes, and cause enhanced death of neurons co
      cultured with inflamed PINK1 -/- mixed glia and neuroblastoma cells exposed to
      conditioned medium from LPS/IFN-gamma treated PINK1 -/- mixed glia. Neuroblastoma
      cell death is prevented with an iNOS inhibitor, implicating increased nitric
      oxide production as the cause for enhanced death. Finally, we show for the first
      time that lack of a recessive PD gene (PINK1) increases alpha-Synuclein-induced
      nitric oxide production in all glia types (mixed glia, astrocytes and microglia).
      Our results describe a novel pathogenic mechanism in recessive PD, where PINK1
      deficiency may increase neuron death via exacerbation of inflammatory stimuli
      induced nitric oxide production and abnormal innate immune responses in glia
      cells.

PMID- 29321621
TI  - Functional Brain Network Mechanism of Hypersensitivity in Chronic Pain.
AB  - Fibromyalgia (FM) is a chronic widespread pain condition characterized by
      augmented multi-modal sensory sensitivity. Although the mechanisms underlying
      this sensitivity are thought to involve an imbalance in excitatory and inhibitory
      activity throughout the brain, the underlying neural network properties
      associated with hypersensitivity to pain stimuli are largely unknown. In network
      science, explosive synchronization (ES) was introduced as a mechanism of
      hypersensitivity in diverse biological and physical systems that display
      explosive and global propagations with small perturbations. We hypothesized that
      ES may also be a mechanism of the hypersensitivity in FM brains. To test this
      hypothesis, we analyzed resting state electroencephalogram (EEG) of 10 FM
      patients. First, we examined theoretically well-known ES conditions within
      functional brain networks reconstructed from EEG, then tested whether a brain
      network model with ES conditions identified in the EEG data is sensitive to an
      external perturbation. We demonstrate for the first time that the FM brain
      displays characteristics of ES conditions, and that these factors significantly
      correlate with chronic pain intensity. The simulation data support the conclusion
      that networks with ES conditions are more sensitive to perturbation compared to
      non-ES network. The model and empirical data analysis provide convergent evidence
      that ES may be a network mechanism of FM hypersensitivity.

PMID- 29321623
TI  - A dual layer broadband radar absorber to minimize electromagnetic interference in
      radomes.
AB  - A thin broadband dual-layer radar absorber based on periodic Frequency Selective
      Surfaces (FSS) to tackle Electromagnetic Interference (EMI) in radomes is
      presented in this article. The proposed structure consists of periodically
      arranged metallic patterns printed on two dielectric substrates separated by an
      optimized air gap. Under normal incidence, the proposed structure exhibits at
      least 89.7% of absorption in the whole band of 4.8 GHz to 11.1 GHz for both
      Transverse Electric (TE) and Magnetic (TM) polarizations. For oblique incidences,
      a very slight decrease in the bandwidth is observed in the upper frequency band
      until 30 degrees  and the absorption remains very interesting for higher
      incidences. The structure is lambda/7.2 (lambda is the wavelength in free space)
      thin compared to the center frequency (8.2 GHz). In addition, parametric studies
      have demonstrated that at least 90% of absorption can be produced with our
      structure by adjusting the thicknesses of the dielectric substrates. Another
      issue that is presented and discussed in this paper is a new approach for
      evaluating the performance of absorbers. In fact, studies show that the absorber
      can compete with other recent broadband absorbers. After fabricating the
      structure, the measurements were found to be in good agreement with the
      simulation results.

PMID- 29321622
TI  - Evaluation of a developmental hierarchy for breast cancer cells to assess risk
      based patient selection for targeted treatment.
AB  - This study proposes that a novel developmental hierarchy of breast cancer (BC)
      cells (BCCs) could predict treatment response and outcome. The continued
      challenge to treat BC requires stratification of BCCs into distinct subsets. This
      would provide insights on how BCCs evade treatment and adapt dormancy for
      decades. We selected three subsets, based on the relative expression of octamer
      binding transcription factor 4 A (Oct4A) and then analysed each with Affymetrix
      gene chip. Oct4A is a stem cell gene and would separate subsets based on
      maturation. Data analyses and gene validation identified three membrane proteins,
      TMEM98, GPR64 and FAT4. BCCs from cell lines and blood from BC patients were
      analysed for these three membrane proteins by flow cytometry, along with known
      markers of cancer stem cells (CSCs), CD44, CD24 and Oct4, aldehyde dehydrogenase
      1 (ALDH1) activity and telomere length. A novel working hierarchy of BCCs was
      established with the most immature subset as CSCs. This group was further
      subdivided into long- and short-term CSCs. Analyses of 20 post-treatment blood
      indicated that circulating CSCs and early BC progenitors may be associated with
      recurrence or early death. These results suggest that the novel hierarchy may
      predict treatment response and prognosis.

PMID- 29321624
TI  - Strong trans-Pacific break and local conservation units in the Galapagos shark
      (Carcharhinus galapagensis) revealed by genome-wide cytonuclear markers.
AB  - The application of genome-wide cytonuclear molecular data to identify management
      and adaptive units at various spatio-temporal levels is particularly important
      for overharvested large predatory organisms, often characterized by smaller,
      localized populations. Despite being "near threatened", current understanding of
      habitat use and population structure of Carcharhinus galapagensis is limited to
      specific areas within its distribution. We evaluated population structure and
      connectivity across the Pacific Ocean using genome-wide single-nucleotide
      polymorphisms (~7200 SNPs) and mitochondrial control region sequences (945 bp)
      for 229 individuals. Neutral SNPs defined at least two genetically discrete
      geographic groups: an East Tropical Pacific (Mexico, east and west Galapagos
      Islands), and another central-west Pacific (Lord Howe Island, Middleton Reef,
      Norfolk Island, Elizabeth Reef, Kermadec, Hawaii and Southern Africa). More fine
      grade population structure was suggested using outlier SNPs: west Pacific,
      Hawaii, Mexico, and Galapagos. Consistently, mtDNA pairwise PhiST defined three
      regional stocks: east, central and west Pacific. Compared to neutral SNPs (FST =
      0.023-0.035), mtDNA exhibited more divergence (PhiST = 0.258-0.539) and high
      overall genetic diversity (h = 0.794 +/- 0.014; pi = 0.004 +/- 0.000), consistent
      with the longstanding eastern Pacific barrier between the east and central-west
      Pacific. Hawaiian and Southern African populations group within the west Pacific
      cluster. Effective population sizes were moderate/high for east/west populations
      (738 and 3421, respectively). Insights into the biology, connectivity, genetic
      diversity, and population demographics informs for improved conservation of this
      species, by delineating three to four conservation units across their Pacific
      distribution. Implementing such conservation management may be challenging, but
      is necessary to achieve long-term population resilience at basin and regional
      scales.

PMID- 29321625
TI  - Cerebellar grey matter modifications in lower limb amputees not using prosthesis.
AB  - Plastic brain changes following peripheral deafferentation, in particular those
      following limb amputations, are well-documented, with significant reduction of
      grey matter (GM) in the sensory-motor cerebral areas representing the amputated
      limb. However, few studies have investigated the role played by the use of a
      prosthesis in these structural brain modifications. Here we hypothesized that
      using a functional prosthesis that allows individuals to perform actions may
      reduce grey matter reduction. We investigated the brain structural reorganization
      following lower limb amputation by using a Voxel Based Morphometry (VBM) analysis
      of structural magnetic resonance imaging (MRI) in 8 right-handed individuals with
      lower limb amputation (LLA) fitted with prostheses (LLAwp), compared to 6 LLA who
      had never used a prosthesis (LLAnp). 14 age-matched healthy controls were also
      enrolled (HC). We did not find any significant effect when comparing LLAwp and
      HC. However we found a decreased GM volume in the bilateral cerebellum in LLAnp
      compared with HC. These results suggest that prosthesis use prevents GM decrease
      in the cerebellum after lower limb amputation.

PMID- 29321626
TI  - Routes to Chaos Induced by a Discontinuous Resetting Process in a Hybrid Spiking
      Neuron Model.
AB  - Several hybrid spiking neuron models combining continuous spike generation
      mechanisms and discontinuous resetting processes following spiking have been
      proposed. The Izhikevich neuron model, for example, can reproduce many spiking
      patterns. This model clearly possesses various types of bifurcations and routes
      to chaos under the effect of a state-dependent jump in the resetting process. In
      this study, we focus further on the relation between chaotic behaviour and the
      state-dependent jump, approaching the subject by comparing spiking neuron model
      versions with and without the resetting process. We first adopt a continuous two
      dimensional spiking neuron model in which the orbit in the spiking state does not
      exhibit divergent behaviour. We then insert the resetting process into the model.
      An evaluation using the Lyapunov exponent with a saltation matrix and a
      characteristic multiplier of the Poincar'e map reveals that two types of chaotic
      behaviour (i.e. bursting chaotic spikes and near-period-two chaotic spikes) are
      induced by the resetting process. In addition, we confirm that this chaotic
      bursting state is generated from the periodic spiking state because of the slow-
      and fast-scale dynamics that arise when jumping to the hyperpolarization and
      depolarization regions, respectively.

PMID- 29321627
TI  - Publisher Correction: A cdk1 gradient guides surface contraction waves in
      oocytes.
AB  - A Supplementary Information file from a different paper was inadvertently
      published with the original version of this Article. This file was replaced with
      the correct Supplementary Information file on 24 October 2017.

PMID- 29321628
TI  - Realizing Mitigation Efficiency of European Commercial Forests by Climate Smart
      Forestry.
AB  - European temperate and boreal forests sequester up to 12% of Europe's annual
      carbon emissions. Forest carbon density can be manipulated through management to
      maximize its climate mitigation potential, and fast-growing tree species may
      contribute the most to Climate Smart Forestry (CSF) compared to slow-growing
      hardwoods. This type of CSF takes into account not only forest resource
      potentials in sequestering carbon, but also the economic impact of regional
      forest products and discounts both variables over time. We used the process-based
      forest model 4 C to simulate European commercial forests' growth conditions and
      coupled it with an optimization algorithm to simulate the implementation of CSF
      for 18 European countries encompassing 68.3 million ha of forest (42.4% of total
      EU-28 forest area). We found a European CSF policy that could sequester 7.3-11.1
      billion tons of carbon, projected to be worth 103 to 141 billion euros in the
      21st century. An efficient CSF policy would allocate carbon sequestration to
      European countries with a lower wood price, lower labor costs, high harvest
      costs, or a mixture thereof to increase its economic efficiency. This policy
      prioritized the allocation of mitigation efforts to northern, eastern and central
      European countries and favored fast growing conifers Picea abies and Pinus
      sylvestris to broadleaves Fagus sylvatica and Quercus species.

PMID- 29321629
TI  - Chiloscyphenol A derived from Chinese liverworts exerts fungicidal action by
      eliciting both mitochondrial dysfunction and plasma membrane destruction.
AB  - This study aimed to characterize the antifungal effects of chiloscyphenol A (CA),
      a natural small molecule isolated from Chinese liverworts, and investigate its
      mode of action. CA was effective against five tested Candida species with a
      minimal inhibitory concentration (MIC) of 8-32 MUg/ml and exhibited fungicidal
      activity against Candida albicans in both the planktonic state and mature
      biofilms. The in vivo study using Caenorhabditis elegans showed that CA prolonged
      the survival of C. albicans infected worms. Further investigations revealed that
      CA resulted in mitochondrial dysfunction as indicated by mtDeltapsi
      hyperpolarization, increased ATP production and intracellular ROS accumulation,
      and aggregated distribution of Tom70. In addition, CA caused perturbation of the
      cell membrane and increased membrane permeability, as demonstrated by specific
      staining and confocal microscopic and transmission electron microscopy (TEM)
      observations and by calcein-leakage measurements. This conclusion was further
      confirmed by the decreased cell size of CA-treated cells via three-dimensional
      contour-plot analysis using flow cytometry. Taken together, these results suggest
      that CA exerts fungicidal activity by eliciting both mitochondrial dysfunction
      and plasma membrane destruction in C. albicans. The elucidated mechanism supports
      the potential application of CA against clinical fungal infections.

PMID- 29321630
TI  - Engineered mesenchymal stem-cell-sheets patches prevents postoperative pancreatic
      leakage in a rat model.
AB  - Post-operative pancreatic fistula (POPF) following pancreatic resection is a life
      threatening surgical complication. Cell sheets were prepared and harvested using
      temperature-responsive culture dishes and transplanted as patches to seal POPF.
      Two different mesenchymal stem cell (MSC) sheets were compared in terms of the
      preventative ability for pancreatic leakage in a rat model. Both rat adipose
      derived stem cell (rADSC) and bone marrow-derived stem cell (rBMSC) sheets were
      transplanted. Those rADSC and rBMSC sheets are created without enzymes and thus
      maintained their cell-cell junctions and adhesion proteins with intact
      fibronectin on the basal side, as well as characteristics of MSCs. The rats with
      post-pancreatectomy rADSC- or rBMSC-sheet patches had significantly decreased
      abdominal fluid leakage compared with the control group, demonstrated by MR image
      analysis and measurement of the volume of abdominal fluid. Amylase level was
      significantly lower in the rats with rADSC-sheet and rBMSC-sheet patches compared
      with the control groups. The rADSC sheet patches had increased adhesive and
      immune-cytokine profiles (ICAM-1, L-selectin, TIMP-1), and the rBMSC sheets had
      reduced immune reactions compared to the control. This is first project looking
      at the feasibility of tissue engineering therapy using MSC-sheets as tissue
      patches preventing leakage of abdominal fluid caused by POPF.

PMID- 29321631
TI  - Stability and anisotropy of (FexNi1-x)2O under high pressure and implications in
      Earth's and super-Earths' core.
AB  - Oxygen is thought to be an important light element in Earth's core but the amount
      of oxygen in Earth's core remains elusive. In addition, iron-rich iron oxides are
      of great interest and significance in the field of geoscience and condensed
      matter physics. Here, static calculations based on density functional theory
      demonstrate that I4/mmm-Fe2O is dynamically and mechanically stable and becomes
      energetically favorable with respect to the assemblage of hcp-Fe and [Formula:
      see text]-FeO above 270 GPa, which indicates that I4/mmm-Fe2O can be a strong
      candidate phase for stable iron-rich iron oxides at high pressure, perhaps even
      at high temperature. The elasticity and anisotropy of I4/mmm-(FexNi1-x)2O at high
      pressures are also determined. Based on these results, we have derived the upper
      limit of oxygen to be 4.3 wt% in Earth's lower outer core. On the other hand,
      I4/mmm-(FexNi1-x)2O with high AV S is likely to exist in a super-Earth's or an
      ocean planet's solid core causing the locally seismic heterogeneity. Our results
      not only give some clues to explore and synthesize novel iron-rich iron oxides
      but also shed light on the fundamental information of oxygen in the planetary
      core.

PMID- 29321632
TI  - Genome-wide association study in Asia-adapted tropical maize reveals novel and
      explored genomic regions for sorghum downy mildew resistance.
AB  - Globally, downy mildews are among the important foliar diseases of maize that
      cause significant yield losses. We conducted a genome-wide association study for
      sorghum downy mildew (SDM; Peronosclerospora sorghi) resistance in a panel of 368
      inbred lines adapted to the Asian tropics. High density SNPs from Genotyping-by
      sequencing were used in GWAS after controlling for population structure and
      kinship in the panel using a single locus mixed model. The study identified a set
      of 26 SNPs that were significantly associated with SDM resistance, with
      Bonferroni corrected P values <= 0.05. Among all the identified SNPs, the minor
      alleles were found to be favorable to SDM resistance in the mapping panel. Trend
      regression analysis with 16 independent genetic variants including 12 SNPs and
      four haplotype blocks identified SNP S2_6154311 on chromosome 2 with P value
      2.61E-24 and contributing 26.7% of the phenotypic variation. Six of the
      SNPs/haplotypes were within the same chromosomal bins as the QTLs for SDM
      resistance mapped in previous studies. Apart from this, eight novel genomic
      regions for SDM resistance were identified in this study; they need further
      validation before being applied in the breeding pipeline. Ten SNPs identified in
      this study were co-located in reported mildew resistance genes.

PMID- 29321634
TI  - Navon's classical paradigm concerning local and global processing relates
      systematically to visual object classification performance.
AB  - Forty years ago David Navon tried to tackle a central problem in psychology
      concerning the time course of perceptual processing: Do we first see the details
      (local level) followed by the overall outlay (global level) or is it rather the
      other way around? He did this by developing a now classical paradigm involving
      the presentation of compound stimuli; large letters composed of smaller letters.
      Despite the usefulness of this paradigm it remains uncertain whether effects
      found with compound stimuli relate directly to visual object recognition. It does
      so because compound stimuli are not actual objects but rather formations of
      elements and because the elements that form the global shape of compound stimuli
      are not features of the global shape but rather objects in their own right. To
      examine the relationship between performance on Navon's paradigm and visual
      object processing we derived two indexes from Navon's paradigm that reflect
      different aspects of the relationship between global and local processing. We
      find that individual differences on these indexes can explain a considerable
      amount of variance in two standard object classification paradigms; object
      decision and superordinate categorization, suggesting that Navon's paradigm does
      relate to visual object processing.

PMID- 29321633
TI  - Olfactory memory is enhanced in mice exposed to extremely low-frequency
      electromagnetic fields via Wnt/beta-catenin dependent modulation of
      subventricular zone neurogenesis.
AB  - Exposure to extremely low-frequency electromagnetic fields (ELFEF) influences the
      expression of key target genes controlling adult neurogenesis and modulates
      hippocampus-dependent memory. Here, we assayed whether ELFEF stimulation affects
      olfactory memory by modulating neurogenesis in the subventricular zone (SVZ) of
      the lateral ventricle, and investigated the underlying molecular mechanisms. We
      found that 30 days after the completion of an ELFEF stimulation protocol (1 mT;
      50 Hz; 3.5 h/day for 12 days), mice showed enhanced olfactory memory and
      increased SVZ neurogenesis. These effects were associated with upregulated
      expression of mRNAs encoding for key regulators of adult neurogenesis and were
      mainly dependent on the activation of the Wnt pathway. Indeed, ELFEF stimulation
      increased Wnt3 mRNA expression and nuclear localization of its downstream target
      beta-catenin. Conversely, inhibition of Wnt3 by Dkk-1 prevented ELFEF-induced
      upregulation of neurogenic genes and abolished ELFEF's effects on olfactory
      memory. Collectively, our findings suggest that ELFEF stimulation increases
      olfactory memory via enhanced Wnt/beta-catenin signaling in the SVZ and point to
      ELFEF as a promising tool for enhancing SVZ neurogenesis and olfactory function.

PMID- 29321635
TI  - Pan-genome analysis of the genus Finegoldia identifies two distinct clades,
      strain-specific heterogeneity, and putative virulence factors.
AB  - Finegoldia magna, a Gram-positive anaerobic coccus, is an opportunistic pathogen,
      associated with medical device-related infections. F. magna is the only described
      species of the genus Finegoldia. We report the analysis of 17 genomes of
      Finegoldia isolates. Phylogenomic analyses showed that the Finegoldia population
      can be divided into two distinct clades, with an average nucleotide identity of
      90.7%. One clade contains strains of F. magna, whereas the other clade includes
      more heterogeneous strains, hereafter tentatively named "Finegoldia nericia". The
      latter species appears to be more abundant in the human microbiome. Surface
      structure differences between strains of F. magna and "F. nericia" were detected
      by microscopy. Strain-specific heterogeneity is high and previously identified
      host-interacting factors are present only in subsets of "F. nericia" and F. magna
      strains. However, all genomes encode multiple host factor-binding proteins such
      as albumin-, collagen-, and immunoglobulin-binding proteins, and two to four
      copies of CAMP (Christie-Atkins-Munch-Petersen) factors; in accordance, most
      strains show a positive CAMP reaction for co-hemolysis. Our work sheds new light
      of the genus Finegoldia and its ability to bind host components. Future research
      should explore if the genomic differences identified here affect the potential of
      different Finegoldia species and strains to cause opportunistic infections.

PMID- 29321636
TI  - Tyrosinase-based TLC Autography for anti-melanogenic drug screening.
AB  - Tyrosinase-based TLC (thin layer chromatography) was developed for screening of
      anti-melanogenic drugs. In particular, this technique enables researchers to
      identify melanogenic inhibitor(s) in tested mixtures with the naked eye. In
      comparison with traditional colorimetric screening assays for tyrosinase
      inhibitor(s), not only is tyrosinase-based TLC a more cost-effective option
      (nearly one-tenth the enzyme cost of colorimetric methods) but also is a more
      sensitive detection approach for kojic acid (KA), a standard anti-melanogenic
      drug. The detection limit of tyrosinase-based TLC and colorimetric tyrosinase
      assay for KA was 0.0125 and 1.25 MUg, respectively, demonstrating that the former
      was 100-fold more sensitive than the latter to determine the tyrosinase
      inhibitory rate of KA. Furthermore, the results of this method have demonstrated
      excellent precision by Gage Repeatability and Reproducibility (Gage R&R), with
      the variation of total Gage R&R being 28.24%. To verify the applicability of
      tyrosinase-based TLC, this platform was employed to screen melanogenic
      inhibitor(s) from Ganoderma formosanum extracts and two of all fractions (GFE-EA
      F4, F5) obtained showed depigmenting activity. It is noteworthy that these two
      fractions also exerted anti-melanogenesis activity on zebrafish, therefore
      verifying the credibility of tyrosinase-based TLC. In sum, this technique
      provides new insight into the discovery of novel melanogenic inhibitor(s).

PMID- 29321639
TI  - Antiphospholipid syndrome.

PMID- 29321637
TI  - Detection of American Football Head Impacts Using Biomechanical Features and
      Support Vector Machine Classification.
AB  - Accumulation of head impacts may contribute to acute and long-term brain trauma.
      Wearable sensors can measure impact exposure, yet current sensors do not have
      validated impact detection methods for accurate exposure monitoring. Here we
      demonstrate a head impact detection method that can be implemented on a wearable
      sensor for detecting field football head impacts. Our method incorporates a
      support vector machine classifier that uses biomechanical features from the time
      domain and frequency domain, as well as model predictions of head-neck motions.
      The classifier was trained and validated using instrumented mouthguard data from
      collegiate football games and practices, with ground truth data labels
      established from video review. We found that low frequency power spectral density
      and wavelet transform features (10~30 Hz) were the best performing features. From
      forward feature selection, fewer than ten features optimized classifier
      performance, achieving 87.2% sensitivity and 93.2% precision in cross-validation
      on the collegiate dataset (n = 387), and over 90% sensitivity and precision on an
      independent youth dataset (n = 32). Accurate head impact detection is essential
      for studying and monitoring head impact exposure on the field, and the approach
      in the current paper may help to improve impact detection performance on wearable
      sensors.

PMID- 29321638
TI  - Enhanced electrocaloric analysis and energy-storage performance of lanthanum
      modified lead titanate ceramics for potential solid-state refrigeration
      applications.
AB  - The unique properties and great variety of relaxer ferroelectrics make them
      highly attractive in energy-storage and solid-state refrigeration technologies.
      In this work, lanthanum modified lead titanate ceramics are prepared and studied.
      The giant electrocaloric effect in lanthanum modified lead titanate ceramics is
      revealed for the first time. Large refrigeration efficiency (27.4) and high
      adiabatic temperature change (1.67 K) are achieved by indirect analysis. Direct
      measurements of electrocaloric effect show that reversible adiabatic temperature
      change is also about 1.67 K, which exceeds many electrocaloric effect values in
      current direct measured electrocaloric studies. Both theoretical calculated and
      direct measured electrocaloric effects are in good agreements in high
      temperatures. Temperature and electric field related energy storage properties
      are also analyzed, maximum energy-storage density and energy-storage efficiency
      are about 0.31 J/cm3 and 91.2%, respectively.

PMID- 29321641
TI  - Antiphospholipid syndrome.
AB  - Antiphospholipid syndrome (APS) is an autoimmune disease characterized by the
      presence of antiphospholipid antibodies, such as lupus anticoagulant,
      anticardiolipin antibodies and anti-beta2-glycoprotein 1 antibodies. APS can
      present with a variety of clinical phenotypes, including thrombosis in the veins,
      arteries and microvasculature as well as obstetrical complications. The
      pathophysiological hallmark is thrombosis, but other factors such as complement
      activation might be important. Prevention of thrombotic manifestations associated
      with APS includes lifestyle changes and, in individuals at high risk, low-dose
      aspirin. Prevention and treatment of thrombotic events are dependent mainly on
      the use of vitamin K antagonists. Immunosuppression and anticomplement therapy
      have been used anecdotally but have not been adequately tested. Pregnancy
      morbidity includes unexplained recurrent early miscarriage, fetal death and late
      obstetrical manifestation such as pre-eclampsia, premature birth or fetal growth
      restriction associated with placental insufficiency. Current treatment to prevent
      obstetrical morbidity is based on low-dose aspirin and/or low-molecular-weight
      heparin and has improved pregnancy outcomes to achieve successful live birth in
      >70% of pregnancies. Although hydroxychloroquine and pravastatin might further
      improve pregnancy outcomes, prospective clinical trials are required to confirm
      these findings.

PMID- 29321640
TI  - Initial evenness determines diversity and cell density dynamics in synthetic
      microbial ecosystems.
AB  - The effect of initial evenness on the temporal trajectory of synthetic
      communities in comprehensive, low-volume microcosm studies remains unknown. We
      used flow cytometric fingerprinting and 16S rRNA gene amplicon sequencing to
      assess the impact of time on community structure in one hundred synthetic
      ecosystems of fixed richness but varying initial evenness. Both methodologies
      uncovered a similar reduction in diversity within synthetic communities of medium
      and high initial evenness classes. However, the results of amplicon sequencing
      showed that there were no significant differences between and within the
      communities in all evenness groups at the end of the experiment. Nevertheless,
      initial evenness significantly impacted the cell density of the community after
      five medium transfers. Highly even communities retained the highest cell
      densities at the end of the experiment. The relative abundances of individual
      species could be associated to particular evenness groups, suggesting that their
      presence was dependent on the initial evenness of the synthetic community. Our
      results reveal that using synthetic communities for testing ecological hypotheses
      requires prior assessment of initial evenness, as it impacts temporal dynamics.

PMID- 29321643
TI  - Magnetoelectricity of CoFe2O4 and tetragonal phase BiFeO3 nanocomposites prepared
      by pulsed laser deposition.
AB  - The coupling between the tetragonal phase (T-phase) of BiFeO3 (BFO) and CoFe2O4
      (CFO) in magnetoelectric heterostructures has been studied. Bilayers of CFO and
      BFO were deposited on (001) LaAlO3 single crystal substrates by pulsed laser
      deposition. After 30 min of annealing, the CFO top layer exhibited a T-phase-like
      structure, developing a platform-like morphology with BFO. Magnetic hysteresis
      loops exhibited a strong thickness effect of the CFO layer on the coercive field,
      in particular along the out-of-plane direction. Magnetic force microscopy images
      revealed that the T-phase CFO platform contained multiple magnetic domains, which
      could be tuned by applying a tip bias. A combination of shape, strain, and
      exchange coupling effects are used to explain the observations.

PMID- 29321642
TI  - Profiling of metabolome and bacterial community dynamics in ensiled Medicago
      sativa inoculated without or with Lactobacillus plantarum or Lactobacillus
      buchneri.
AB  - Using gas chromatography mass spectrometry and the PacBio single molecule with
      real-time sequencing technology (SMRT), we analyzed the detailed metabolomic
      profiles and microbial community dynamics involved in ensiled Medicago sativa
      (alfalfa) inoculated without or with the homofermenter Lactobacillus plantarum or
      heterofermenter Lactobacillus buchneri. Our results revealed that 280 substances
      and 102 different metabolites were present in ensiled alfalfa. Inoculation of L.
      buchneri led to remarkable up-accumulation in concentrations of 4-aminobutyric
      acid, some free amino acids, and polyols in ensiled alfalfa, whereas considerable
      down-accumulation in cadaverine and succinic acid were observed in L. plantarum
      inoculated silages. Completely different microbial flora and their successions
      during ensiling were observed in the control and two types of inoculant-treated
      silages. Inoculation of the L. plantarum or L. buchneri alters the microbial
      composition dynamics of the ensiled forage in very different manners. Our study
      demonstrates that metabolomic profiling analysis provides a deep insight in
      metabolites in silage. Moreover, the PacBio SMRT method revealed the microbial
      composition and its succession during the ensiling process at the species level.
      This provides information regarding the microbial processes underlying silage
      formation and may contribute to target-based regulation methods to achieve high
      quality silage production.

PMID- 29321646
TI  - Continuous-wave Y-band planar BWO with wide tunable bandwidth.
AB  - A high performance continuous-wave (CW) backward wave oscillator (BWO) with
      planar slow wave structure (SWS) and sheet electron beam in Y-band is presented
      in this paper. The mode selection is discussed by studying the dispersion curve
      of SWSs, distributions of the electric field, and particle-in-cell simulation
      results, showing that the designed BWO operates in the fundamental mode TM11. The
      planar SWSs are fabricated by using the UV-LIGA technology with the processing
      error less than 0.003 mm. The electron gun can provide the 2.5 mm * 0.14 mm sheet
      electron beam with maximum current density of 57 A/cm2 at the CW mode.
      Experimental results show that the developed BWO can operate in the fundamental
      mode TM11 and generate the state-of-art output power of 182 mW at the frequency
      of 0.3426 THz with a large frequency tuning range from 0.318 THz to 0.359 THz.

PMID- 29321645
TI  - MRI features predictive of negative surgical margins in patients with HER2
      overexpressing breast cancer undergoing breast conservation.
AB  - Here we develop a tool to predict resectability of HER2+ breast cancer at breast
      conservation surgery (BCS) utilizing features identified on preoperative breast
      MRI. We identified patients with HER2+ breast cancer who obtained pre-operative
      breast MRI and underwent BCS between 2002-2013. From the contoured tumor on pre
      operative MRI, shape, histogram, and co-occurrence and size zone matrix texture
      features were extracted. In univariate analysis, Spearman's correlation
      coefficient (Rs) was used to assess the correlation between each image feature
      and an endpoint (surgical re-excision). For multivariate modeling, we employed a
      support vector machine (SVM) method in a manner of leave-one-out cross-validation
      (LOOCV). Of 109 patients with HER2+breast cancer who underwent BCS, 39% underwent
      surgical re-excision. 62% had residual cancer at re-excision. In univariate
      analysis, solidity (Rs = -0.32, p = 0.009) and extent (Rs = -0.29, p = 0.019)
      were significantly associated with re-excision. Skewness in post-contrast 1, 2,
      and 3 (Rs = 0.25, p = 0.045; Rs = 0.30, p = 0.015; Rs = 0.28, p = 0.026) and
      kurtosis in post-contrast 1 (Rs = 0.26, p = 0.035) were also statistically
      significant. LOOCV-based SVM test achieved 74.4% specificity and 71.4%
      sensitivity when 21 features were used. Thus, tumor texture, histogram and
      morphological MRI features may assist surgical planning, encouraging wide margins
      or mastectomy in patients who may otherwise go on to re-excision.

PMID- 29321644
TI  - COX-2 induces oncogenic micro RNA miR655 in human breast cancer.
AB  - We show that Cyclooxygenase-2 over-expression induces an oncogenic microRNA
      miR655 in human breast cancer cells by activation of EP4. MiR655 expression
      positively correlated with COX-2 in genetically disparate breast cancer cell
      lines and increased in all cell lines when grown as spheroids, implicating its
      link with stem-like cells (SLCs). Ectopic miR655 over-expression in MCF7 and
      SKBR3 cells resulted in increased proliferation, migration, invasion, spheroid
      formation and Epithelial to Masenchymal transition (EMT). Conversely, knocking
      down miR655 in aggressive MCF7-COX2 and SKBR3-COX2 cells reverted these
      phenotypes. MCF7-miR655 cells displayed upregulated NOTCH/WNT genes; both pathway
      inhibitors abrogated miR655-induced spheroid formation, linking miR655 with SLC
      related pathways. MiR655 expression was dependent on EP4 activity and EP4
      downstream signaling pathways PI3K/AKT, ERK and NF-kB and led to TGFbeta
      resistance for Smad3 phosphorylation. Tail vein injection of MCF7-miR655 and
      SKBR3-miR655 cells in NOD/SCID/GUSB-null mice revealed increased lung colony
      growth and micrometastases to liver and spleen. MiR655 expression was
      significantly high in human breast tumors (n = 105) compared to non-tumor tissues
      (n = 20) and associated with reduced patient survival. Thus miR655 could serve as
      a prognostic breast cancer biomarker.

PMID- 29321647
TI  - Molecular marker assisted breeding and genome composition analysis of Zhengmai
      7698, an elite winter wheat cultivar.
AB  - Zhengmai 7698 is an elite winter wheat variety widely cultivated in the Southern
      regions of the Yellow-Huai River Valley of China. Here, we report the molecular
      markers used for breeding Zhengmai 7698 and the genome composition of this
      cultivar revealed using genome-wide SNPs. A total of 26 DNA markers derived from
      the genes controlling gluten protein quality, grain hardness, flour color,
      disease resistance, or pre-harvesting sprouting resistance were used during
      breeding. Consequently, Zhengmai 7698 had strong gluten, high grain hardness
      index, white flour color, and high levels of resistance to powdery mildew, stripe
      rust infections, and pre-harvesting sprouting. Using genome complexity reduction,
      28,996 high-quality SNPs distributed on 21 wheat chromosomes were identified
      among Zhengmai 7698 and its three parental lines (4B269, Zhengmai 9405 and
      Zhoumai 16). Zhengmai 7698 shared 12,776, 14,411 and 16,085 SNPs with 4B269,
      Zhengmai 9405 and Zhoumai 16, respectively. Thus, the contributions of 4B269,
      Zhengmai 9405 and Zhoumai 16 to the genome of Zhengmai 7698 were comparable.
      Interestingly, Zhengmai 7698 had 307 unique SNPs that are absent in all three
      parents. We suggest that molecular markers facilitate selection of a wheat
      cultivar with multiple elite traits. Analysis of genome composition with SNPs may
      provide useful clues for further dissecting the genetic basis of improved wheat
      performance.

PMID- 29321648
TI  - Comparative analysis of miRNA expression profiles in transgenic and non
      transgenic rice using miRNA-Seq.
AB  - Safety assessment for genetically modified organisms (GMOs) is required before
      their release. To date, miRNAs that play important roles in eukaryotic gene
      regulation have not been considered in the current assessment system. In this
      study, we identified 6 independent Bt and EPSPS GM rice lines using PCR and
      immune strip. We analyzed the expression levels of Cry1Ac and EPSPS using
      quantitative real-time PCR and western blot. Further, miRNAs from the developing
      seeds of the 6 GM rice lines and the wild-type line were investigated using deep
      sequencing and bioinformatic approaches. Although these GM lines have different
      types of integration sites, copy numbers, and levels of gene expression, 21
      differentially expressed miRNAs have been found compared to wild type. There is
      no correlation between transgenic protein expression level and the quantity of
      differentially expressed miRNAs. This study provides useful data about the miRNA
      composition of GM plants, and it might be helpful for future risk assessments of
      miRNA-based GM plants.

PMID- 29321649
TI  - Face size biases emotion judgment through eye movement.
AB  - Faces are the most commonly used stimuli to study emotions. Researchers often
      manipulate the emotion contents and facial features to study emotion judgment,
      but rarely manipulate low-level stimulus features such as face sizes. Here, I
      investigated whether a mere difference in face size would cause differences in
      emotion judgment. Subjects discriminated emotions in fear-happy morphed faces.
      When subjects viewed larger faces, they had an increased judgment of fear and
      showed a higher specificity in emotion judgment, compared to when they viewed
      smaller faces. Concurrent high-resolution eye tracking further provided
      mechanistic insights: subjects had more fixations onto the eyes when they viewed
      larger faces whereas they had a wider dispersion of fixations when they viewed
      smaller faces. The difference in eye movement was present across fixations in
      serial order but independent of morph level, ambiguity level, or behavioral
      judgment. Together, this study not only suggested a link between emotion judgment
      and eye movement, but also showed importance of equalizing stimulus sizes when
      comparing emotion judgments.

PMID- 29321650
TI  - RNA-Seq analysis and comparison of corneal epithelium in keratoconus and myopia
      patients.
AB  - Keratoconus is a common degenerative corneal disease that can lead to significant
      visual morbidity, and both genetic and environmental factors have been implicated
      in its pathogenesis. We compared the transcriptome of keratoconus and control
      epithelium using RNA-Seq. Epithelial tissues were obtained prior to surgery from
      keratoconus and myopia control patients, undergoing collagen cross-linking and
      photorefractive keratectomy, respectively. We identified major differences in
      keratoconus linked to cell-cell communication, cell signalling and cellular
      metabolism. The genes associated with the Hedgehog, Wnt and Notch1 signaling
      pathways were down-regulated in keratoconus. We also identified plasmolipin and
      Notch1 as being significantly reduced in keratoconus for both gene and protein
      expression (p < 0.05). Plasmolipin is a novel protein identified in human corneal
      epithelium, and has been demonstrated to have a key role in epithelial cell
      differentiation in other tissues. This study shows altered gene and protein
      expression of these three proteins in keratoconus, and further studies are
      clearly warranted to confirm the functional role of these proteins in the
      pathogenesis of keratoconus.

PMID- 29321651
TI  - Auditory Neural Activity in Congenitally Deaf Mice Induced by Infrared Neural
      Stimulation.
AB  - To determine whether responses during infrared neural stimulation (INS) result
      from the direct interaction with spiral ganglion neurons (SGNs), we tested three
      genetically modified deaf mouse models: Atoh1-cre; Atoh1 f/f (Atoh1 conditional
      knockout, CKO), Atoh1-cre; Atoh1 f/kiNeurog1 (Neurog1 knockin, KI), and the
      Vglut3 knockout (Vglut3 -/-) mice. All animals were exposed to tone bursts and
      clicks up to 107 dB (re 20 uPa) and to INS, delivered with a 200 um optical
      fiber. The wavelength (lambda) was 1860 nm, the radiant energy (Q) 0-800
      uJ/pulse, and the pulse width (PW) 100-500 us. No auditory responses to acoustic
      stimuli could be evoked in any of these animals. INS could not evoke auditory
      brainstem responses in Atoh1 CKO mice but could in Neurog1 KI and Vglut3 -/-
      mice. X-ray micro-computed tomography of the cochleae showed that responses
      correlated with the presence of SGNs and hair cells. Results in Neurog1 KI mice
      do not support a mechanical stimulation through the vibration of the basilar
      membrane, but cannot rule out the direct activation of the inner hair cells.
      Results in Vglut3 -/- mice, which have no synaptic transmission between inner
      hair cells and SGNs, suggested that hair cells are not required.

PMID- 29321652
TI  - Innate IFN-gamma ameliorates experimental autoimmune encephalomyelitis and
      promotes myeloid expansion and PDL-1 expression.
AB  - The innate immune system plays a central role in the immune-mediated pathology of
      multiple sclerosis, and is a therapeutic target for progressive disease.
      Recently, it has been demonstrated that MIS416, a novel immunomodulatory
      microparticle that activates NOD-2 and TLR-9-signaling, has disease-modifying
      activity in multiple sclerosis models. This activity is dependent on innate IFN
      gamma; however, the precise immune regulatory mechanisms amplified by MIS416 have
      not previously been determined. Using the experimental autoimmune
      encephalomyelitis model, MIS416 treatment was associated with IFN-gamma-dependant
      expansion of Treg number and increased suppressive function; however, these cells
      did not account for disease reduction. Additionally, MIS416 treatment stimulated
      increased nitric oxide production that was IFN-gamma-dependant but dispensable
      for protection. Finally, MIS416-mediated protection was shown to correlate with
      IFN-gamma-dependant expansion of PDL-1-expressing peripheral myeloid cells, a
      subset of which was found to be selectively recruited to the brain. This central
      nervous system trafficking was independent of neuro-inflammatory signals as it
      occurred in MIS416-treated healthy mice. Together, these findings provide insight
      into regulatory myeloid cell activities amplified by MIS416-mediated NOD-2 and
      TLR-9 signalling and highlight the potential importance of these cells in
      accessing the brain where they may act locally and contribute to the control of
      neuroinflammation.

PMID- 29321653
TI  - Integrated sequencing of exome and mRNA of large-sized single cells.
AB  - Current approaches of single cell DNA-RNA integrated sequencing are difficult to
      call SNPs, because a large amount of DNA and RNA is lost during DNA-RNA
      separation. Here, we performed simultaneous single-cell exome and transcriptome
      sequencing on individual mouse oocytes. Using microinjection, we kept the nuclei
      intact to avoid DNA loss, while retaining the cytoplasm inside the cell membrane,
      to maximize the amount of DNA and RNA captured from the single cell. We then
      conducted exome-sequencing on the isolated nuclei and mRNA-sequencing on the
      enucleated cytoplasm. For single oocytes, exome-seq can cover up to 92% of exome
      region with an average sequencing depth of 10+, while mRNA-sequencing reveals
      more than 10,000 expressed genes in enucleated cytoplasm, with similar
      performance for intact oocytes. This approach provides unprecedented
      opportunities to study DNA-RNA regulation, such as RNA editing at single
      nucleotide level in oocytes. In future, this method can also be applied to other
      large cells, including neurons, large dendritic cells and large tumour cells for
      integrated exome and transcriptome sequencing.

PMID- 29321654
TI  - Motivating Cord Blood Donation with Information and Behavioral Nudges.
AB  - Umbilical cord blood is a source of hematopoietic stem cells essential to treat
      life-threatening diseases, such as leukemia and lymphoma. However, only a very
      small percentage of parents donate upon delivery. The decision to donate the cord
      blood occurs at a very specific time and when parents likely experience
      emotional, informational, and decisional overloads; these features of cord blood
      donation make it different from other pro-social activities. In collaboration
      with an OB-GYN clinic in Milan, Italy, we conducted the first randomized
      controlled trial that applies tools from behavioral science to foster cord blood
      donation, and quantified the gains that informational and behavioral "nudges" can
      achieve. We found that information and "soft" commitments increased donations;
      approaching expecting parents closer to the delivery date and providing them with
      multiple reminders, moreover, had the strongest impact. However, a significant
      portion of women who expressed consent to donate could not do so because of
      organizational constraints. We conclude that simple, non-invasive behavioral
      interventions that address information gaps and procrastination, and that
      increase the salience of the activity can substantially enhance altruistic
      donations of cord blood, especially when coupled with organizational support.

PMID- 29321656
TI  - Evolution of poled state in P(VDF-TrFE)/(Pb,Ba)(Zr,Ti)O3 composites probed by
      temperature dependent Piezoresponse and Kelvin Probe Force Microscopy.
AB  - Polarized states of polymer/inorganic inclusion P(VDF-TrFE)-(Pb,Ba)(Zr,Ti)O3
      composites are studied at the nanoscale using both piezoresponse force microscopy
      (PFM) and Kelvin probe force microscopy (KPFM). It has been shown that inorganic
      inclusions can be visualized using KPFM due to a discontinuity of the surface
      potential and polarization at the interface between the inclusions and the
      polymer matrix. The temperature evolution of the PFM and KPFM signal profiles is
      investigated. Softening of the polymer matrix on approaching the Curie
      temperature limits application of the contact PFM method. However non-contact
      KPFM can be used to probe evolution of the polarization at the phase transition.
      Mechanisms of the KPFM contrast formation are discussed.

PMID- 29321657
TI  - Room temperature stable film formation of pi-conjugated organic molecules on 3d
      magnetic substrate.
AB  - An important step toward molecule-based electronics is to realize a robust and
      well-ordered molecular network at room temperature. To this end, one key
      challenge is tuning the molecule-substrate electronic interactions that influence
      not only the molecular selfassembly but also the stability of the resulting
      structures. In this study, we investigate the film formation of pi-conjugated
      metal-free phthalocyanine molecules on a 3d-bcc-Fe(001) whisker substrate at 300
      K by using ultra-high-vacuum scanning tunneling microscopy. On bare Fe(001),
      hybridization between the molecular pi and the Fe(001) d-states prevents the
      molecular assembly, resulting in the disordered patchy structures. The second-
      and third-layer molecules form densely packed films, while the morphologies show
      clear difference. The second-layer molecules partially form p(5 * 5)-ordered
      films with the rectangular edges aligned along the [100] and [010] directions,
      while the edges of the third-layer films are rounded. Remarkably, such film
      morphologies are stable even at 300 K. These findings suggest that the molecular
      self-assembly and the resulting morphologies in the second and third layers are
      affected by the substrate bcc(001), despite that the Fe-d states hybridize only
      with the first-layer molecules. The possible mechanism is discussed with the
      kinetic Monte Carlo simulation.

PMID- 29321655
TI  - Evaluation of Brain Activity Using Near-infrared Spectroscopy in Inflammatory
      Bowel Disease Patients.
AB  - Depression is implicated as a risk factor for the recurrence of inflammatory
      bowel disease (IBD). Near-infrared spectroscopy (NIRS) and brain-derived
      neurotrophic factor (BDNF) are useful tools for evaluation of brain activity and
      a depressive state, respectively. The aim of this study was to clarify the
      association between brain activity or depressive symptoms and IBD using NIRS and
      BDNF. This study included 36 ulcerative colitis (UC) patients, 32 Crohn's disease
      (CD) patients, and 17 healthy controls (HC). Center for Epidemiologic Studies
      Depression Scale (CES-D) scores were determined, NIRS was performed, and serum
      BDNF levels were measured in all subjects. NIRS showed that the mean oxygenated
      hemoglobin concentration was significantly lower in the frontal lobe in the UC
      group than in the HC group (HC 167 +/- 106 vs. UC 83.1 +/- 85.3, p < 0.05). No
      significant difference was seen between the HC and CD groups. There were also no
      significant differences in CED-D scores and BDNF levels among the groups. Changes
      in the NIRS values of the UC group may indicate decreased brain activity and a
      fundamental difference between UC and CD, which are often lumped together as two
      types of IBD.

PMID- 29321658
TI  - Slower Time estimation in Post-Traumatic Stress Disorder.
AB  - Cognitive deficits in Posttraumatic Stress Disorder (PTSD) and dissociative
      symptoms suggest there may be an underlying and persistent problem with temporal
      processing in PTSD, but this question has not been systematically examined. We
      investigated the ability of a group of PTSD participants in estimating the
      duration of supra-second visual stimuli relative to healthy controls. The data of
      59 participants with PTSD and 62 healthy controls, collected from the BRID
      database, have been examined. Overall, our results indicate that PTSD patients
      overestimate the duration of the displayed stimuli. Moreover, we found that PTSD
      are more variable in the time estimation compared to the control group. Finally,
      we found evidence that working memory and attention impairments were associated
      with time overestimation in PTSD. The finding of time overestimation in PTSD
      accords with previous reports of time overestimation during stressful experiences
      associated with fear and arousal, but extends findings to suggest it remains in
      chronic PTSD populations processing non-emotional stimuli. The evidence of time
      overestimation in PTSD suggests the potential relevance of this factor as a
      cognitive marker in assessing the neuropsychological profile of this clinical
      population.

PMID- 29321661
TI  - Differential recruitment of CD44 isoforms by ErbB ligands reveals an involvement
      of CD44 in breast cancer.
AB  - Members of the CD44 family of transmembrane glycoproteins control cell signaling
      pathways from numerous cell surface receptors, including receptor tyrosine
      kinases (RTKs). The decisive factor (ligand, RTKs or both) that controls the
      recruitment of specific CD44 isoforms is still unknown. We investigated this
      question by using the EGFR signaling pathway, in which one receptor can be
      activated by a broad range of ligands. By means of siRNA-mediated downregulation
      of CD44 expression and blocking experiments, we identified CD44v6 as a co
      receptor for EGF- and ER-induced ErbB1 activation and for NRG1-induced ErbB3 and
      ErbB4 activation. In contrast, TGFalpha is independent of all CD44 isoforms, even
      though it addresses the same receptor pairs as EGF. Moreover, the heparin
      sulfated CD44v3 isoform is required for HB-EGF-induced EGFR signaling. These data
      suggest that specific CD44 isoforms are recruited in a ligand-dependent manner as
      co-receptors in the EGFR signaling pathways and that the specificity is
      determined by the ligand and not by the receptors themselves. The in vivo
      relevance of this interplay between CD44 isoforms and EGFR ligands is underlined
      by the decreased metastatic spreading of mammary carcinomas in mice treated with
      a CD44v6-specific peptide. Most importantly, we found a clear correlation between
      the presence of CD44v6/ErbB1 complexes in breast cancer patients and lymph node
      metastases.

PMID- 29321659
TI  - Epidermal growth factor receptor and EGFRvIII in glioblastoma: signaling pathways
      and targeted therapies.
AB  - Amplification of epidermal growth factor receptor (EGFR) and its active mutant
      EGFRvIII occurs frequently in glioblastoma (GBM). While EGFR and EGFRvIII play
      critical roles in pathogenesis, targeted therapy with EGFR-tyrosine kinase
      inhibitors (TKIs) or antibodies has only shown limited efficacy in patients. Here
      we discuss signaling pathways mediated by EGFR/EGFRvIII, current therapeutics,
      and novel strategies to target EGFR/EGFRvIII-amplified GBM.

PMID- 29321660
TI  - Activated ALK signals through the ERK-ETV5-RET pathway to drive neuroblastoma
      oncogenesis.
AB  - Activating mutations of the ALK receptor occur in a subset of neuroblastoma
      tumors. We previously demonstrated that Alk mutations cooperate with MYCN
      overexpression to induce neuroblastoma in mice and identified Ret as being
      strongly upregulated in MYCN/Alkmut tumors. By a genetic approach in vivo, we now
      document an oncogenic cooperation between activated Ret and MYCN overexpression
      in neuroblastoma formation. We show that MYCN/RetM919T tumors exhibit
      histological features and expression profiles close to MYCN/Alkmut tumors. We
      show that RET transcript levels decrease precedes RET protein levels decrease
      upon ALK inhibition in neuroblastoma cell lines. Etv5 was identified as a
      candidate transcription factor regulating Ret expression from murine MYCN/Alkmut
      tumor transcriptomic data. We demonstrate that ETV5 is regulated both at the
      protein and mRNA levels upon ALK activation or inhibition in neuroblastoma cell
      lines and that this regulation precedes RET modulation. We document that ALK
      activation induces ETV5 protein upregulation through stabilization in a MEK/ERK
      dependent manner. We show that RNAi-mediated inhibition of ETV5 decreases RET
      expression. Reporter assays indicate that ETV5 is able to drive RET gene
      transcription. ChIP-seq analysis confirmed ETV5 binding on the RET promoter and
      identified an enhancer upstream of the promoter. Finally, we demonstrate that
      combining RET and ALK inhibitors reduces tumor growth more efficiently than each
      single agent in MYCN and AlkF1178L-driven murine neuroblastoma. Altogether, these
      results define the ERK-ETV5-RET pathway as a critical axis driving neuroblastoma
      oncogenesis downstream of activated ALK.

PMID- 29321662
TI  - Breast cancer metastasis to liver and lung is facilitated by Pit-1-CXCL12-CXCR4
      axis.
AB  - Development of human tumors is driven by accumulation of alterations in tumor
      suppressor genes and oncogenes in cells. The POU1F1 transcription factor (also
      known Pit-1) is expressed in the mammary gland and its overexpression induces
      profound phenotypic changes in proteins involved in breast cancer progression.
      Patients with breast cancer and elevated expression of Pit-1 show a positive
      correlation with the occurrence of distant metastasis and poor overall survival.
      However, some mediators of Pit-1 actions are still unknown. Here, we show that
      CXCR4 chemokine receptor and its ligand CXCL12 play a critical role in the pro
      tumoral process induced by Pit-1. We found that Pit-1 increases mRNA and protein
      in both CXCR4 and CXCL12. Knock-down of CXCR4 reduces tumor growth and spread of
      Pit-1 overexpressing cells in a zebrafish xenograft model. Furthermore, we
      described for the first time pro-angiogenic effects of Pit-1 through the CXCL12
      CXCR4 axis, and that extravasation of Pit-1 overexpressing breast cancer cells is
      strongly reduced in CXCL12-deprived target tissues. Finally, in breast cancer
      patients, expression of Pit-1 in primary tumors was found to be positively
      correlated with CXCR4 and CXCL12, with specific metastasis in liver and lung, and
      with clinical outcome. Our results suggest that Pit-1-CXCL12-CXCR4 axis could be
      involved in chemotaxis guidance during the metastatic process, and may represent
      prognostic and/or therapeutic targets in breast tumors.

PMID- 29321663
TI  - LPA signaling is regulated through the primary cilium: a novel target in
      glioblastoma.
AB  - The primary cilium is a ubiquitous organelle presented on most human cells. It is
      a crucial signaling hub for multiple pathways including growth factor and G
      protein coupled receptors. Loss of primary cilia, observed in various cancers,
      has been shown to affect cell proliferation. Primary cilia formation is
      drastically decreased in glioblastoma (GBM), however, the role of cilia in normal
      astrocyte or glioblastoma proliferation has not been explored. Here, we report
      that loss of primary cilia in human astrocytes stimulates growth rate in a
      lysophosphatidic acid (LPA)-dependent manner. We show that lysophosphatidic acid
      receptor 1 (LPAR1) is accumulated in primary cilia. LPAR1 signaling through
      Galpha12/Galphaq was previously reported to be responsible for cancer cell
      proliferation. We found that in ciliated cells, Galpha12 and Galphaq are excluded
      from the cilium, creating a barrier against unlimited proliferation, one of the
      hallmarks of cancer. Upon loss of primary cilia, LPAR1 redistributes to the
      plasma membrane with a concomitant increase in LPAR1 association with Galpha12
      and Galphaq. Inhibition of LPA signaling with the small molecule compound Ki16425
      in deciliated highly proliferative astrocytes or glioblastoma patient-derived
      cells/xenografts drastically suppresses their growth both in vitro and in vivo.
      Moreover, Ki16425 brain delivery via PEG-PLGA nanoparticles inhibited tumor
      progression in an intracranial glioblastoma PDX model. Overall, our findings
      establish a novel mechanism by which primary cilium restricts proliferation and
      indicate that loss of primary cilia is sufficient to increase mitogenic
      signaling, and is important for the maintenance of a highly proliferative
      phenotype. Clinical application of LPA inhibitors may prove beneficial to
      restrict glioblastoma growth and ensure local control of disease.

PMID- 29321664
TI  - Mitochondrial fission and mitophagy depend on cofilin-mediated actin
      depolymerization activity at the mitochondrial fission site.
AB  - Mitochondria fission and mitophagy are fundamentally crucial to cellular
      physiology and play important roles in cancer progression. Developing a
      comprehensive understanding of the molecular mechanism underlying mitochondrial
      fission and mitophagy will provide novel strategies for cancer prevention and
      treatment. Actin has been shown to participate in mitochondrial fission and
      mitophagy regulation. Cofilin is best known as an actin-depolymerizing factor.
      However, the molecular mechanism by which cofilin regulates mitochondrial fission
      and mitophagy remains largely unknown. Here we report that knockdown of cofilin
      attenuates and overexpression of cofilin potentiates mitochondrial fission as
      well as PINK1/PARK2-dependent mitophagy induced by staurosporine (STS), etoposide
      (ETO), and carbonyl cyanide 3-chlorophenylhydrazone (CCCP). Cofilin-mediated
      PINK1 (PTEN-induced putative kinase 1) accumulation mainly depends on its
      regulation of mitochondrial proteases, including peptidase mitochondrial
      processing beta (MPPbeta), presenilin-associated rhomboid-like protease (PARL),
      and ATPase family gene 3-like 2 (AFG3L2), via mitochondrial membrane potential
      activity. We also found that the interaction and colocalization of G-actin/F
      actin with cofilin at mitochondrial fission sites undergo constriction after CCCP
      treatment. Pretreatment with the actin polymerization inhibitor latrunculin B
      (LatB) increased and actin-depolymerization inhibitor jasplakinolide (Jas)
      decreased mitochondrial translocation of actin induced by STS, ETO, and CCCP.
      Both LatB and Jas abrogated CCCP-mediated mitochondrial fission and mitophagy.
      Our data suggest that G-actin is the actin form that is translocated to
      mitochondria, and the actin-depolymerization activity regulated by cofilin at the
      mitochondrial fission site is crucial for inducing mitochondrial fission and
      mitophagy.

PMID- 29321665
TI  - FHL2 interacts with EGFR to promote glioblastoma growth.
AB  - Four-and-a-half LIM protein2 (FHL2) is a member of the LIM-only protein family,
      which plays a critical role in tumorigenesis. We previously reported that FHL2 is
      upregulated and plays an oncogenic role in glioblastoma (GBM), the most common
      and aggressive brain tumor. GBM is also marked by amplification of the epidermal
      growth factor receptor (EGFR) gene and its mutations, of which EGFRvIII is the
      most common and functionally significant. Here we report that FHL2 physically
      interacts with the wild-type EGFR and its mutated EGFRvIII form in GBM cells.
      Expression of FHL2 caused increased EGFR and EGFRvIII protein levels and this was
      due to an increase in protein stability rather than an increase in EGFR mRNA
      expression. In contrast, FHL2 knockdown using RNA interference reduced EGFR and
      EGFRvIII protein expression and the phosphorylation levels of EGFR and AKT.
      Consistent with these features, EGFR expression was significantly lower in mouse
      FHL2-null astrocytes, where reintroduction of FHL2 was able to restore EGFR
      levels. Using established GBM cell lines and patient-derived neurosphere lines,
      FHL2 silencing markedly induced cell apoptosis in EGFRvIII-positive cells.
      Targeting FHL2 significantly prevented EGFRvIII-positive GBM tumor growth in
      vivo. FHL2 expression also positively correlated with EGFR expression in GBM
      samples from patients. Taken together, our results demonstrate that FHL2
      interacts with EGFR and EGFRvIII to increase their levels and this promotes
      glioma growth, representing a novel mechanism that may be therapeutically
      targetable.

PMID- 29321666
TI  - Are there multiple cells of origin of Merkel cell carcinoma?
AB  - Merkel cell carcinoma (MCC) is a rare but lethal cancer with the highest case-by
      case fatality rate among all skin cancers. Eighty percent of cancers are
      associated with the Merkel cell polyomavirus (MCPyV). Twenty percent of MCCs are
      virus negative. Recent epidemiological data suggest that there are important,
      clinically relevant differences between these two subtypes of MCC. Recent studies
      in cancer genomics, mouse genetics, and virology experiments have transformed our
      understanding of MCC pathophysiology. Importantly, dramatic differences in the
      genetics of these two MCC subtypes suggest fundamental differences in their
      pathophysiology. We review these recent works and find that they provocatively
      suggest that MCPyV-positive and MCPyV-negative MCCs arise from two different
      cells of origin: the MCPyV-negative MCC from epidermal keratinocytes and the
      MCPyV-positive MCC from dermal fibroblasts. If true, this would represent the
      first cancer that we are aware of that evolves from cells of origin from two
      distinct germ layers: MCPyV-negative MCCs from ectodermal keratinocytes and MCPyV
      positive MCCs from mesodermal fibroblasts. Future epigenetic experiments may
      prove valuable in confirming these distinct lineages for these MCC subtypes,
      especially for the clinical importance the cell of origin has on MCC treatment
      and prevention.

PMID- 29321667
TI  - The management of retinoblastoma.
AB  - Retinoblastoma (Rb) is the most common primary intraocular malignancy of
      childhood, but an uncommon paediatric cancer, with a constant incidence worldwide
      of 1:15,000-1:20,000 live births. Despite its rarity, Rb has served as a
      cornerstone in the field of oncology in many of the aspects that comprise cancer
      management, including classification schemes, treatment modalities, genetic
      testing and screening. Until just over half a century ago, the major treatment
      for Rb was eye removal, and prognosis was poor with outcome fatal for most
      children. The dramatic evolution, in a short period of time across all fields of
      Rb management, as well as the development of specialized centres, better
      infrastructure and introduction of awareness campaigns, has resulted in nearly
      100% survival in developed countries and allowed eye salvage in many of the
      cases. External beam radiotherapy was used as the main treatment choice for four
      decades, but replaced by chemotherapy at the turn of the century. Initially, and
      still in many centres, chemotherapy is administered intravenously, but recently
      is targeted directly into the eye by means of intra-ophthalmic artery and
      intravitreal chemotherapy. To date, a range of treatments is available to the Rb
      expert, including enucleation, but there is lack of consensus in a number of
      scenarios as to what to use and when. In such a rare cancer, treatment outcomes
      are reported usually via retrospective analyses, with few prospective randomized
      controlled trials. Classification schemes have also evolved following the
      introduction of new treatment modalities, but discrepancies exist among centres
      with respect to the preferred schema and its interpretation. Retinoblastoma
      management is a remarkable success story, but the future will require a
      collaborative effort in the form of multicentre randomized controlled trials in
      order to further improve the quality of care for this subset of young children
      with ocular cancer.

PMID- 29321669
TI  - Phenotypic characteristics of colorectal cancer in BRCA1/2 mutation carriers.
AB  - Mutations in the BRCA1/2 genes were recently shown to be associated with an
      increased risk for colorectal cancer. We characterized the largest cohort
      available of BRCA1/2 mutation carriers with colorectal cancer. We analyzed 32
      patients with lower gastrointestinal cancers and germline BRCA1/2 mutations from
      two large academic hospital registries; 91% of patients were of Ashkenazi
      ancestry, 78% were women, and 62.5% were carriers of BRCA1 gene mutations. A high
      percentage of colorectal tumors (34.5%) had a mucinous histology and were located
      atypically in the left colon. Two patients had anal cancer with unusual histology
      and an additional patient had mucinous small bowel carcinoma. Gene expression
      analysis showed significant correlation between the gene signatures of left
      mucinous colorectal cancer and basal-like breast cancer. Our results imply that
      Ashkenazi BRCA1/2 mutation carriers with colorectal cancer might have unique
      characteristics with a high rate of left-sided, mucinous histology colorectal
      cancer, and possibly anal carcinoma. This report suggests a phenotypic influence
      of defects in DNA repair genes on colorectal tumors.

PMID- 29321668
TI  - AATF suppresses apoptosis, promotes proliferation and is critical for Kras-driven
      lung cancer.
AB  - A fundamental principle in malignant tranformation is the ability of cancer cells
      to escape the naturally occurring cell-intrinsic responses to DNA damage. Tumors
      progress despite the accumulation of DNA lesions. However, the underlying
      mechanisms of this tolerance to genotoxic stress are still poorly characterized.
      Here, we show that replication stress occurs in Kras-driven murine lung
      adenocarcinomas, as well as in proliferating murine embryonic and adult tissues.
      We identify the transcriptional regulator AATF/CHE-1 as a key molecule to sustain
      proliferative tissues and tumor progression in parts by inhibiting p53-driven
      apoptosis in vivo. In an autochthonous Kras-driven lung adenocarcinoma model,
      deletion of Aatf delayed lung cancer formation predominantly in a p53-dependent
      manner. Moreover, targeting Aatf in existing tumors through a dual recombinase
      strategy caused a halt in tumor progression. Taken together, these data suggest
      that AATF may serve as a drug target to treat KRAS-driven malignancies.

PMID- 29321671
TI  - Preconception carrier screening for multiple disorders: evaluation of a screening
      offer in a Dutch founder population.
AB  - Technological developments have enabled carrier screening for multiple disorders.
      This study evaluated experiences with a preconception carrier screening offer for
      four recessive disorders in a Dutch founder population. Questionnaires were
      completed by 182 attendees pretesting and posttesting and by 137 non-attendees.
      Semistructured interviews were conducted with seven of the eight carrier couples.
      Attendees were mainly informed about the existence of screening by
      friends/colleagues (49%) and family members (44%). Familiarity with the genetic
      disorders was high. Knowledge after counseling increased (p < 0.001); however,
      still 9%, compared to 29% before counseling, wrongly mentioned an increased risk
      of having an affected child if both parents are carriers of different disorders.
      Most attendees (97%) recalled their test results correctly, but two couples
      reported being carrier of another disorder than reported. Overall, 63% felt
      worried while waiting for results but anxiety levels returned to normal
      afterwards. In all, 2/39 (5%) carriers felt less healthy. Screened individuals
      were very satisfied; they did not regret testing (97%) and would recommend
      testing to others (97%). The majority (94%) stated that couples should always
      have a pretest consultation, preferably by a genetic counselor rather than their
      general practitioner (83%). All carrier couples made reproductive decisions based
      on their results. Main reason for non-attendance was unawareness of the screening
      offer. With expanded carrier screening, adequately informing couples pretest and
      posttesting is of foremost importance. Close influencers (family/friends) can be
      used to raise awareness of a screening offer. Our findings provide lessons for
      the implementation of expanded carrier screening panels in other communities and
      other settings.

PMID- 29321670
TI  - Clinical and experimental evidence suggest a link between KIF7 and C5orf42
      related ciliopathies through Sonic Hedgehog signaling.
AB  - Acrocallosal syndrome (ACLS) is an autosomal recessive neurodevelopmental
      disorder caused by KIF7 defects and belongs to the heterogeneous group of
      ciliopathies related to Joubert syndrome (JBTS). While ACLS is characterized by
      macrocephaly, prominent forehead, depressed nasal bridge, and hypertelorism,
      facial dysmorphism has not been emphasized in JBTS cohorts with molecular
      diagnosis. To evaluate the specificity and etiology of ACLS craniofacial
      features, we performed whole exome or targeted Sanger sequencing in patients with
      the aforementioned overlapping craniofacial appearance but variable additional
      ciliopathy features followed by functional studies. We found (likely) pathogenic
      variants of KIF7 in 5 out of 9 families, including the original ACLS patients,
      and delineated 1000 to 4000-year-old Swiss founder alleles. Three of the
      remaining families had (likely) pathogenic variants in the JBTS gene C5orf42, and
      one patient had a novel de novo frameshift variant in SHH known to cause
      autosomal dominant holoprosencephaly. In accordance with the patients'
      craniofacial anomalies, we showed facial midline widening after silencing of
      C5orf42 in chicken embryos. We further supported the link between KIF7, SHH, and
      C5orf42 by demonstrating abnormal primary cilia and diminished response to a SHH
      agonist in fibroblasts of C5orf42-mutated patients, as well as axonal pathfinding
      errors in C5orf42-silenced chicken embryos similar to those observed after
      perturbation of Shh signaling. Our findings, therefore, suggest that beside the
      neurodevelopmental features, macrocephaly and facial widening are likely more
      general signs of disturbed SHH signaling. Nevertheless, long-term follow-up
      revealed that C5orf42-mutated patients showed catch-up development and fainting
      of facial features contrary to KIF7-mutated patients.

PMID- 29321673
TI  - Genomic analysis of family data reveals additional genetic effects on
      intelligence and personality.
AB  - Pedigree-based analyses of intelligence have reported that genetic differences
      account for 50-80% of the phenotypic variation. For personality traits these
      effects are smaller, with 34-48% of the variance being explained by genetic
      differences. However, molecular genetic studies using unrelated individuals
      typically report a heritability estimate of around 30% for intelligence and
      between 0 and 15% for personality variables. Pedigree-based estimates and
      molecular genetic estimates may differ because current genotyping platforms are
      poor at tagging causal variants, variants with low minor allele frequency, copy
      number variants, and structural variants. Using ~20,000 individuals in the
      Generation Scotland family cohort genotyped for ~700,000 single-nucleotide
      polymorphisms (SNPs), we exploit the high levels of linkage disequilibrium (LD)
      found in members of the same family to quantify the total effect of genetic
      variants that are not tagged in GWAS of unrelated individuals. In our models,
      genetic variants in low LD with genotyped SNPs explain over half of the genetic
      variance in intelligence, education, and neuroticism. By capturing these
      additional genetic effects our models closely approximate the heritability
      estimates from twin studies for intelligence and education, but not for
      neuroticism and extraversion. We then replicated our finding using imputed
      molecular genetic data from unrelated individuals to show that ~50% of
      differences in intelligence, and ~40% of the differences in education, can be
      explained by genetic effects when a larger number of rare SNPs are included. From
      an evolutionary genetic perspective, a substantial contribution of rare genetic
      variants to individual differences in intelligence, and education is consistent
      with mutation-selection balance.

PMID- 29321672
TI  - Phenotypic interpretation of complex chromosomal rearrangements informed by
      nucleotide-level resolution and structural organization of chromatin.
AB  - Molecular characterization of balanced chromosomal abnormalities constitutes a
      powerful tool in understanding the pathogenic mechanisms of complex genetic
      disorders. Here we report a male with severe global developmental delay in the
      presence of a complex karyotype and normal microarray and exome studies. The
      subject, referred to as DGAP294, has two de novo apparently balanced
      translocations involving chromosomes 1 and 14, and chromosomes 4 and 10,
      disrupting several different transcripts of adhesion G protein-coupled receptor
      L2 (ADGRL2) and protocadherin 15 (PCDH15). In addition, a maternally inherited
      inversion disrupts peptidyl arginine deiminase types 3 and 4 (PADI3 and PADI4) on
      chromosome 1. None of these gene disruptions explain the patient's phenotype.
      Using genome regulatory annotations and chromosome conformation data, we predict
      a position effect ~370 kb upstream of a translocation breakpoint located at
      14q12. The position effect involves forkhead box G1 (FOXG1), mutations in which
      are associated with the congenital form of Rett syndrome and FOXG1 syndrome. We
      believe the FOXG1 position effect largely accounts for the clinical phenotype in
      DGAP294, which can be classified as FOXG1 syndrome like. Our findings emphasize
      the significance of not only analyzing disrupted genes by chromosomal
      rearrangements, but also evaluating potential long-range position effects in
      clinical diagnoses.

PMID- 29321674
TI  - Body mass index, waist circumference, and waist-to-height ratio for prediction of
      multiple metabolic risk factors in Chinese elderly population.
AB  - The purpose of this study was to compare the predictive ability of five obesity
      indices, including body mass index (BMI), waist circumference (WC), waist-to
      height ratio (WHtR), waist-to-hip ratio (WHpR) and body adiposity index (BAI), to
      predict multiple non-adipose metabolic risk factors, including elevated blood
      pressure (BP), elevated fasting plasma glucose (FPG), elevated triglyceride (TG),
      reduced high-density lipoprotein cholesterol (HDL-C), elevated serum uric acid
      (SUA) and non-alcoholic fatty liver disease (NAFLD), in an elderly Chinese
      population. A total of 5685 elderly Chinese subjects (>=60 years) were recruited
      into our community-based cross-sectional study. Receiver operating characteristic
      curve (ROC) analyses were used to compare the predictive ability as well as
      determine the optimal cut-off values of the obesity indices for multiple
      metabolic risk factors. According to the areas under the receiver operating
      characteristic curve (AUC), BMI, WC and WHtR were able to similarly predict high
      metabolic risk in males (0.698 vs. 0.691 vs. 0.688), while in females, BMI and WC
      were able to similarly predict high metabolic risk (0.676 vs. 0.669). The optimal
      cut-off values of BMI, WC and WHtR in males were, respectively, 24.12 kg/m2, 83.5
      cm and 0.51, while in females, the values were 23.53 kg/m2 and 77.5 cm.

PMID- 29321676
TI  - Synthesis of Wurtzite Cu2ZnSnS4 Nanosheets with Exposed High-Energy (002) Facets
      for Fabrication of Efficient Pt-Free Solar Cell Counter Electrodes.
AB  - Two-dimensional (2D) semiconducting nanomaterials have generated much interest
      both because of fundamental scientific interest and technological applications
      arising from the unique properties in two dimensions. However, the colloidal
      synthesis of 2D quaternary chalcogenide nanomaterials remains a great challenge
      owing to the lack of intrinsic driving force for its anisotropic growth. 2D
      wurtzite Cu2ZnSnS4 nanosheets (CZTS-NS) with high-energy (002) facets have been
      obtained for the first time via a simple one-pot thermal decomposition method.
      The CZTS-NS exhibits superior photoelectrochemical activity as compared to zero
      dimensional CZTS nanospheres and comparable performance to Pt counter electrode
      for dye sensitized solar cells. The improved catalytic activity can be attributed
      to additional reactive catalytic sites and higher catalytic reactivity in high
      energy (002) facets of 2D CZTS-NS. This is in accordance with the density
      functional theory (DFT) calculations, which indicates that the (002) facets of
      wurtzite CZTS-NS possess higher surface energy and exhibits remarkable
      reducibility for I3- ions. The developed synthetic method and findings will be
      helpful for the design and synthesis of 2D semiconducting nanomaterials,
      especially eco-friendly copper chalcogenide nanocrystals for energy harvesting
      and photoelectric applications.

PMID- 29321675
TI  - Overexpression of a constitutively active truncated form of OsCDPK1 confers
      disease resistance by affecting OsPR10a expression in rice.
AB  - The rice pathogenesis-related protein OsPR10a was scarcely expressed in OsCDPK1
      silenced (Ri-1) rice, which was highly sensitive to pathogen infection. After
      inoculating the leaves with bacterial blight (Xanthomonas oryzae pv. oryzae;
      Xoo), we found that the expression of OsPR10a was up- and down-regulated in OEtr
      1 (overexpression of the constitutively active truncated form of OsCDPK1) and Ri
      1 rice plants, respectively. OsPR10a and OsCDPK1 showed corresponding expression
      patterns and were up-regulated in response to the jasmonic acid, salicylic acid
      and Xoo treatments, and OsPR1 and OsPR4 were significantly up-regulated in OEtr
      1. These results suggest that OsCDPK1 may be an upstream regulator involved in
      rice innate immunity and conferred broad-spectrum of disease resistance.
      Following the Xoo inoculation, the OEtr-1 and Ri-1 seedlings showed enhanced and
      reduced disease resistance, respectively. The dihybrid rice Ri-1/OsPR10a-Ox not
      only bypassed the effect of OsCDPK1 silencing on the susceptibility to Xoo but
      also showed enhanced disease resistance and, consistent with Ri-1 phenotypes,
      increased plant height and grain size. Our results reveal that OsCDPK1 plays
      novel key roles in the cross-talk and mediation of the balance between stress
      response and development and provides a clue for improving grain yield and
      disease resistance simultaneously in rice.

PMID- 29321677
TI  - Recognition by host nuclear transport proteins drives disorder-to-order
      transition in Hendra virus V.
AB  - Hendra virus (HeV) is a paramyxovirus that causes lethal disease in humans, for
      which no vaccine or antiviral agent is available. HeV V protein is central to
      pathogenesis through its ability to interact with cytoplasmic host proteins,
      playing key antiviral roles. Here we use immunoprecipitation, siRNA knockdown and
      confocal laser scanning microscopy to show that HeV V shuttles to and from the
      nucleus through specific host nuclear transporters. Spectroscopic and small angle
      X-ray scattering studies reveal HeV V undergoes a disorder-to-order transition
      upon binding to either importin alpha/beta1 or exportin-1/Ran-GTP, dependent on
      the V N-terminus. Importantly, we show that specific inhibitors of nuclear
      transport prevent interaction with host transporters, and reduce HeV infection.
      These findings emphasize the critical role of host-virus interactions in HeV
      infection, and potential use of compounds targeting nuclear transport, such as
      the FDA-approved agent ivermectin, as anti-HeV agents.

PMID- 29321679
TI  - Responses of Intrinsic Water-use Efficiency and Tree Growth to Climate Change in
      Semi-Arid Areas of North China.
AB  - Tree-level intrinsic water-use efficiency (iWUE) is derived from the tree-ring
      13C isotope composition (delta13C) and is an important indicator of the
      adaptability for trees to climate change. However, there is still uncertainty
      regarding the relationship between long-term forest ecosystem carbon
      sequestration capacity and iWUE. To determine whether elevated atmospheric CO2
      concentration (Ca) increase iWUE and tree growth (basal area increment, BAI),
      dendrochronological methods and stable isotope analyses were used to examine
      annual changes in the tree-ring width and carbon isotope composition (delta13C)
      of Platycladus orientalis in northern China. The iWUE derived from delta13C has
      increased significantly (p < 0.01). Long-term iWUE trend was largely and
      positively driven by the elevated atmospheric CO2 concentration and temperature.
      We observed a general increase in averaged BAI, which had significant positive
      correlation with iWUE (R2 = 0.3186, p < 0.01). Increases in iWUE indeed
      translated into enhanced P. orientalis growth in semi-arid areas of northern
      China. Elevated atmospheric CO2 concentration significantly (p < 0.01) stimulated
      P. orientalis biomass accumulation when Ca was less than approximately 320 ppm in
      the early phase; however, this effect was not pronounced when Ca exceeded 320
      ppm.

PMID- 29321678
TI  - Systems pharmacology analysis of synergy of TCM: an example using saffron
      formula.
AB  - Traditional Chinese medicine (TCM) follows the principle of formulae, in which
      the pharmacological activity of a single herb can be enhanced or potentiated by
      addition of other herbs. Nevertheless, the involved synergy mechanisms in
      formulae remain unknown. Here, a systems-based method is proposed and applied to
      three representative Chinese medicines in compound saffron formula (CSF): two
      animal spices (Moschus, Beaver Castoreum), and one herb Crocus sativus which
      exert synergistic effects for cardiovascular diseases (CVDs). From the formula,
      42 ingredients and 66 corresponding targets are acquired based on the ADME
      evaluation and target fishing model. The network relationships between the
      compounds and targets are assembled with CVDs pathways to elucidate the
      synergistic therapeutic effects between the spices and the herbs. The results
      show that different compounds of the three medicines show similar curative
      activity in CVDs. Additionally, the active compounds from them shared CVDs
      relevant targets (multiple compounds-one target), or functional diversity targets
      but with clinical relevance (multiple compounds-multiple targets-one disease).
      Moreover, the targets of them are largely enriched in the same CVDs pathways
      (multiple targets-one pathway). These results elucidate why animal spices and
      herbs can have pharmacologically synergistic effects on CVDs, which provides a
      new way for drug discovery.

PMID- 29321680
TI  - Cryptic transmission of ST405 Escherichia coli carrying bla NDM-4 in hospital.
AB  - Three carbapenem-resistant Escherichia coli were recovered from rectal swabs of
      different patients in a tertiary hospital and were found carrying bla NDM-4, an
      uncommon bla NDM variant. Genome sequences of the isolates were obtained using
      Illumina technology and the long-read MinION sequencer. The isolates belonged to
      ST405 and phylogenetic group D, a globally distributed lineage associated with
      antimicrobial resistance. In addition to bla NDM-4, the three isolates carried 14
      known resistance genes including the extended-spectrum beta-lactamase gene bla
      CTX-M-15. There were only 1 or 2 SNPs between the isolates, suggesting a common
      origin and cryptic transmission in hospital. bla NDM-4 was located on a 46.5-kb
      IncFIA self-transmissible plasmid, which may facilitate further dissemination of
      bla NDM-4. Two copies of IS26 bracketed a 14.6-kb region containing bla NDM-4 and
      have the potential to form a composite transposon for mediating the mobilization
      of bla NDM-4.

PMID- 29321681
TI  - In vivo monitoring of hair cycle stages via bioluminescence imaging of hair
      follicle NG2 cells.
AB  - Hair growth occurs periodically in a cycle that consists of three different
      phases: growth, regression, and resting. The length of each phase is regulated by
      both intrinsic and extrinsic factors throughout life, and influenced by
      physiological and pathological conditions. Elongation of the resting phase and
      shortening of the growth phase occur during physiological ageing and in baldness,
      respectively. In vivo discrimination of each phase of the hair cycle can be used
      to research for regeneration of hair follicles as well as to evaluate the
      efficacy of hair regrowth treatments in the same individual. Here we show that
      NG2+ epithelial cells in the hair follicles encompass bulge stem cells, and that
      the number of hair follicle NG2 cells underwent dramatic changes during the hair
      cycle. Transgenic rats with expression of firefly luciferase gene in NG2 cells
      were generated to monitor the hair cycle in vivo. Hair follicle NG2 cells were
      clearly visualized via bioluminescence imaging to study each phase of the hair
      cycle in the rats, from infancy to old age.

PMID- 29321685
TI  - Physical activity and diet on atherogenic index of plasma among adults in the
      United States: mediation considerations by central adiposity.
AB  - BACKGROUND/OBJECTIVES: The potential interactive or combined association of
      moderate-to-vigorous physical activity (MVPA) and dietary behavior with
      atherogenic index of plasma (AIP) has yet to be explored in a representative
      sample of US adults. Thus, the study aim was to examine the association of MVPA
      and dietary behavior on AIP, with potential mediation considerations by central
      adiposity. SUBJECTS/METHODS: Data from the National Health and Nutrition
      Examination Survey were used (N = 2701 adults aged 20-85 years). AIP was
      evaluated via blood sample, MVPA was assessed via accelerometry, and two 24-h
      recalls were utilized to calculate Healthy Eating Index (HEI), a metric of
      dietary quality. Android-specific dual energy X-ray absorptiometry (DXA) was used
      to measure central adiposity. RESULTS: Meeting MVPA guidelines (OR = 0.58; 95%
      CI: 0.41-0.82; P = 0.004), but not meeting dietary guidelines (OR = 0.89; 95% CI:
      0.69-1.15; P = 0.37), was associated with reduced odds of having an elevated
      (>0.24 mmol/L) AIP. Having one (OR = 0.68; 95% CI: 0.52-0.89; P = 0.007) or both
      (OR = 0.55; 95% CI: 0.37-0.82; P = 0.005) health-enhancing behaviors (adequate
      physical activity and/or healthy diet), when compared to having neither, was
      associated with reduced odds (32 and 45%) for having an elevated AIP. The
      relative excess risk due to interaction (RERI) was 0.06 (95% CI: -0.06 to 0.18; P
      = 0.31), suggesting there is no additive interaction between MVPA and dietary
      behavior on AIP. All associations were attenuated when including central
      adiposity as a covariate, suggesting a mediation effect of central adiposity.
      CONCLUSIONS: MVPA is independently associated with reduced odds of having an
      elevated AIP, having both adequate levels of MVPA and a healthy diet does not
      substantively reduce the odds of AIP, and there is no additive interaction effect
      between MVPA and diet on AIP. Central adiposity mediated the relationship between
      MVPA and AIP.

PMID- 29321683
TI  - Dual function of thalamic low-vigilance state oscillations: rhythm-regulation and
      plasticity.
AB  - During inattentive wakefulness and non-rapid eye movement (NREM) sleep, the
      neocortex and thalamus cooperatively engage in rhythmic activities that are
      exquisitely reflected in the electroencephalogram as distinctive rhythms spanning
      a range of frequencies from <1 Hz slow waves to 13 Hz alpha waves. In the
      thalamus, these diverse activities emerge through the interaction of cell
      intrinsic mechanisms and local and long-range synaptic inputs. One crucial
      feature, however, unifies thalamic oscillations of different frequencies:
      repetitive burst firing driven by voltage-dependent Ca2+ spikes. Recent evidence
      reveals that thalamic Ca2+ spikes are inextricably linked to global
      somatodendritic Ca2+ transients and are essential for several forms of thalamic
      plasticity. Thus, we propose herein that alongside their rhythm-regulation
      function, thalamic oscillations of low-vigilance states have a plasticity
      function that, through modifications of synaptic strength and cellular
      excitability in local neuronal assemblies, can shape ongoing oscillations during
      inattention and NREM sleep and may potentially reconfigure thalamic networks for
      faithful information processing during attentive wakefulness.

PMID- 29321686
TI  - Effect of monitoring salt concentration of home-prepared dishes and using low
      sodium seasonings on sodium intake reduction.
AB  - BACKGROUND/OBJECTIVES: Objective methods such as the monitoring of salt
      concentrations in home-prepared dishes may be effective in reducing salt intake.
      We investigated the effect of monitoring the salt concentration of home-prepared
      dishes (Monitoring) on salt reduction and change in taste threshold, and the
      effect of the simultaneous use of low-sodium seasonings (Seasoning) to compare
      the effect of Monitoring with the conventional method. SUBJECTS/METHODS: We
      conducted a double-blind randomized controlled study using a 2 * 2 factorial
      design with two interventions. A total of 50 participants (40-75 years-old) were
      recruited among residents of Niigata Prefecture, a high sodium-consuming
      population in Japan, then randomly allocated to four groups. After excluding
      participants with incomplete urine collection, change in salt intake was
      evaluated using 24-hour urinary excretion as a surrogate of intake for 43
      participants. Change in taste threshold was evaluated in 48 participants after
      excluding those with incomplete threshold measurement. RESULTS: The Monitoring
      intervention group showed a significant decrease in sodium intake (-777 mg/24 h),
      whereas the decrease in the Seasoning intervention group was not significant (
      413 mg/24 h). Sodium intake did not statistically differ between the intervention
      and control groups (-1011 mg/24 h and -283 mg/24 h for Monitoring and Seasoning,
      respectively). The changes in taste threshold measurement were very small and did
      not markedly differ between groups. CONCLUSIONS: Monitoring the salt
      concentration of dishes had a potentially stronger salt-reducing effect than the
      use of low-sodium seasonings, a conventional method. Confirmation requires
      additional study with a larger sample size.

PMID- 29321682
TI  - Intermittent metabolic switching, neuroplasticity and brain health.
AB  - During evolution, individuals whose brains and bodies functioned well in a fasted
      state were successful in acquiring food, enabling their survival and
      reproduction. With fasting and extended exercise, liver glycogen stores are
      depleted and ketones are produced from adipose-cell-derived fatty acids. This
      metabolic switch in cellular fuel source is accompanied by cellular and molecular
      adaptations of neural networks in the brain that enhance their functionality and
      bolster their resistance to stress, injury and disease. Here, we consider how
      intermittent metabolic switching, repeating cycles of a metabolic challenge that
      induces ketosis (fasting and/or exercise) followed by a recovery period (eating,
      resting and sleeping), may optimize brain function and resilience throughout the
      lifespan, with a focus on the neuronal circuits involved in cognition and mood.
      Such metabolic switching impacts multiple signalling pathways that promote
      neuroplasticity and resistance of the brain to injury and disease.

PMID- 29321687
TI  - Impact of biofortified maize consumption on serum carotenoid concentrations in
      Zambian children.
AB  - Biofortified maize, designed as an intervention strategy to prevent vitamin A
      deficiency, can provide upwards of 15 MUg beta-carotene per g dry weight. Some
      varieties also have elevated concentrations of other carotenoids. We conducted a
      cluster randomized, controlled feeding trial in rural Zambia to test the impact
      of daily consumption of biofortified maize over a 6-month period on vitamin A
      status. Serum concentrations of retinol and carotenoids were assessed by high
      performance liquid chromatography. Data on circulating carotenoids by
      intervention group in 679 children are reported here. As previously shown,
      consumption of this beta-carotene-rich maize significantly improved serum beta
      carotene concentrations (0.273 vs. 0.147 MUmol/L, p < 0.001, in this subset of
      children). Here we show significant increases in alpha-carotene, beta
      cryptoxanthin, and zeaxanthin (p < 0.001). There was no impact on lutein or
      lycopene concentrations. Consumption of biofortified maize can have broader
      implications beyond the control of vitamin A deficiency (Trial registration:
      NCT01695148).

PMID- 29321684
TI  - Leptin and the maintenance of elevated body weight.
AB  - Obesity represents the single most important risk factor for early disability and
      death in developed societies, and the incidence of obesity remains at staggering
      levels. CNS systems that modulate energy intake and expenditure in response to
      changes in body energy stores serve to maintain constant body adiposity; the
      adipocyte-derived hormone leptin and its receptor (LEPR) represent crucial
      regulators of these systems. As in the case of insulin resistance, a variety of
      mechanisms (including feedback inhibition, inflammation, gliosis and endoplasmic
      reticulum stress) have been proposed to interfere with leptin action and impede
      the systems that control body energy homeostasis to promote or maintain obesity,
      although the relative importance and contribution of each of these remain
      unclear. However, LEPR signalling may be increased (rather than impaired) in
      common obesity, suggesting that any obesity-associated defects in leptin action
      must result from lesions somewhere other than the initial LEPR signal. It is also
      possible that increased LEPR signalling could mediate some of the obesity
      associated changes in hypothalamic function.

PMID- 29321688
TI  - Changes in nutritional care after implementing national guidelines-a 10-year
      follow-up study.
AB  - BACKGROUND/OBJECTIVES: In 2004, a survey conducted in Scandinavia documented
      insufficient knowledge in nutrition care among doctors and nurses. The survey
      also revealed a significant discrepancy in nutritional practice, where Norway
      ranked lowest, thus leading to several actions including elaboration of national
      guidelines. The aim of this study was to evaluate potential changes in
      nutritional practice, as well as assessing barriers to nutrition therapy, 10
      years after the former study. SUBJECTS/METHODS: In the first half of 2014, a
      total of 4000 doctors and nurses received a questionnaire, similar to the one
      used in 2004. The questions dealt with nutritional practice, routines, knowledge,
      barriers, and use of clinical dietitians (CDs) in the hospitals. RESULTS: The
      response rate was 22%. Routines in nutritional practice were significantly
      improved. The level of knowledge among respondents were increased, but lack of
      knowledge and lack of assignment of responsibility were still important barriers.
      The patients' contradiction could be a barrier to the use of enteral nutrition.
      CDs are used in a small amount of patients, and wards with good nutritional
      routines have a better cooperation with CDs than wards with insufficient
      routines. CONCLUSIONS: Routines in clinical nutrition have improved from 2004 to
      2014. Barriers in the daily practice among health care workers like lack of
      knowledge and lack of assignment of responsibility are still important, and
      health care professionals seem to let the patient himself or herself be a barrier
      to the use of enteral nutrition.

PMID- 29321689
TI  - Analysis of Combined Transcriptomes Identifies Gene Modules that Differentially
      Respond to Pathogenic Stimulation of Vascular Smooth Muscle and Endothelial
      Cells.
AB  - Smooth muscle cells (SMCs) and endothelial cells (ECs) are vital cell types
      composing the vascular medial wall and the atheroprotective inner lining,
      respectively. Current treatments for cardiovascular disease inhibit SMC
      hyperplasia but compromise EC integrity, predisposing patients to thrombosis.
      Therapeutics targeting SMCs without collateral damage to ECs are highly
      desirable. However, differential (SMC versus EC) disease-associated regulations
      remain poorly defined. We conducted RNA-seq experiments to investigate SMC-versus
      EC differential transcriptomic dynamics, following treatment of human primary
      SMCs and ECs with TNFalpha or IL-1beta, both established inducers of SMC
      hyperplasia and EC dysfunction. As revealed by combined SMC/EC transcriptomes,
      after TNFalpha or IL-1beta induction, 174 and 213 genes respectively showed
      greater up-regulation in SMCs than in ECs (SMC-enriched), while 117 and 138 genes
      showed greater up-regulation in ECs over SMCs (EC-enriched). Analysis of gene
      interaction networks identified central genes shared in the two SMC-enriched gene
      sets, and a distinct group of central genes common in the two EC-enriched gene
      sets. Significantly, four gene modules (subnetworks) were identified from these
      central genes, including SMC-enriched JUN and FYN modules and EC-enriched SMAD3
      and XPO1 modules. These modules may inform potential intervention targets for
      selective blockage of SMC hyperplasia without endothelial damage.

PMID- 29321690
TI  - Evidence for energetic tradeoffs between physical activity and childhood growth
      across the nutritional transition.
AB  - Despite broad implications for understanding human life history, energetics, and
      health, the impact of physical activity on childhood growth remains unclear.
      Particularly understudied is the effect of secular changes in physical activity
      on child development. We address these shortcomings using data spanning the
      transition from traditional to semi-developed economy among Yucatec Maya
      agriculturalists. Anthropometric and behavioral observation data were collected
      from children living in a subsistence-based rural community in 1992 and again in
      2012 following the introduction of a school and mechanized technologies but
      minimal overt dietary change. Multiple regression analyses demonstrate dramatic
      twenty-year transformations in how children spent their time. This behavioral
      change was associated with large declines in estimated physical activity level
      (PAL), associated activity energy expenditure savings of several hundred
      kilocalories/day, and sizable increases in mean height, weight, and triceps
      skinfold thickness. Controlling for observed frequency of market food
      consumption, PAL was inversely related to child body size and subcutaneous fat
      stores and significantly mediated the effects of data collection year on
      anthropometric indices. These findings indicate that physical activity can
      considerably influence childhood growth, highlighting the role of energy
      allocation tradeoffs between physical activity and competing life tasks in
      shaping patterns of human ontogeny and health.

PMID- 29321691
TI  - Deciphering the nature of the coral-Chromera association.
AB  - Since the discovery of Chromera velia as a novel coral-associated microalga, this
      organism has attracted interest because of its unique evolutionary position
      between the photosynthetic dinoflagellates and the parasitic apicomplexans. The
      nature of the relationship between Chromera and its coral host is controversial.
      Is it a mutualism, from which both participants benefit, a parasitic
      relationship, or a chance association? To better understand the interaction,
      larvae of the common Indo-Pacific reef-building coral Acropora digitifera were
      experimentally infected with Chromera, and the impact on the host transcriptome
      was assessed at 4, 12, and 48 h post-infection using Illumina RNA-Seq technology.
      The transcriptomic response of the coral to Chromera was complex and implies that
      host immunity is strongly suppressed, and both phagosome maturation and the
      apoptotic machinery is modified. These responses differ markedly from those
      described for infection with a competent strain of the coral mutualist
      Symbiodinium, instead resembling those of vertebrate hosts to parasites and/or
      pathogens such as Mycobacterium tuberculosis. Consistent with ecological studies
      suggesting that the association may be accidental, the transcriptional response
      of A. digitifera larvae leads us to conclude that Chromera could be a coral
      parasite, commensal, or accidental bystander, but certainly not a beneficial
      mutualist.

PMID- 29321692
TI  - Geobacteraceae are important members of mercury-methylating microbial communities
      of sediments impacted by waste water releases.
AB  - Microbial mercury (Hg) methylation in sediments can result in bioaccumulation of
      the neurotoxin methylmercury (MMHg) in aquatic food webs. Recently, the discovery
      of the gene hgcA, required for Hg methylation, revealed that the diversity of Hg
      methylators is much broader than previously thought. However, little is known
      about the identity of Hg-methylating microbial organisms and the environmental
      factors controlling their activity and distribution in lakes. Here, we combined
      high-throughput sequencing of 16S rRNA and hgcA genes with the chemical
      characterization of sediments impacted by a waste water treatment plant that
      releases significant amounts of organic matter and iron. Our results highlight
      that the ferruginous geochemical conditions prevailing at 1-2 cm depth are
      conducive to MMHg formation and that the Hg-methylating guild is composed of iron
      and sulfur-transforming bacteria, syntrophs, and methanogens.
      Deltaproteobacteria, notably Geobacteraceae, dominated the hgcA carrying
      communities, while sulfate reducers constituted only a minor component, despite
      being considered the main Hg methylators in many anoxic aquatic environments.
      Because iron is widely applied in waste water treatment, the importance of
      Geobacteraceae for Hg methylation and the complexity of Hg-methylating
      communities reported here are likely to occur worldwide in sediments impacted by
      waste water treatment plant discharges and in iron-rich sediments in general.

PMID- 29321694
TI  - Statistical power to detect violation of the proportional hazards assumption when
      using the Cox regression model.
AB  - The use of the Cox proportional hazards regression model is widespread. A key
      assumption of the model is that of proportional hazards. Analysts frequently test
      the validity of this assumption using statistical significance testing. However,
      the statistical power of such assessments is frequently unknown. We used Monte
      Carlo simulations to estimate the statistical power of two different methods for
      detecting violations of this assumption. When the covariate was binary, we found
      that a model-based method had greater power than a method based on cumulative
      sums of martingale residuals. Furthermore, the parametric nature of the
      distribution of event times had an impact on power when the covariate was binary.
      Statistical power to detect a strong violation of the proportional hazards
      assumption was low to moderate even when the number of observed events was high.
      In many data sets, power to detect a violation of this assumption is likely to be
      low to modest.

PMID- 29321693
TI  - Human mesenchymal stem cells lose their functional properties after paclitaxel
      treatment.
AB  - Mesenchymal stem cells (MSCs) are an integral part of the bone marrow niche and
      aid in the protection, regeneration and proliferation of hematopoietic stem cells
      after exposure to myelotoxic taxane anti-cancer agents, but the influence of
      taxane compounds on MSCs themselves remains incompletely understood. Here, we
      show that bone marrow-derived MSCs are highly sensitive even to low
      concentrations of the prototypical taxane compound paclitaxel. While MSCs
      remained metabolically viable, they were strongly impaired regarding both their
      proliferation and their functional capabilities after exposure to paclitaxel.
      Paclitaxel treatment resulted in reduced cell migration, delays in cellular
      adhesion and significant dose-dependent inhibition of the stem cells'
      characteristic multi-lineage differentiation potential. Cellular morphology and
      expression of the defining surface markers remained largely unaltered. Paclitaxel
      only marginally increased apoptosis in MSCs, but strongly induced premature
      senescence in these stem cells, thereby explaining the preservation of the
      metabolic activity of functionally inactivated MSCs. The reported sensitivity of
      MSC function to paclitaxel treatment may help to explain the severe bone marrow
      toxicities commonly caused by taxane-based anti-cancer treatments.

PMID- 29321695
TI  - ?
AB  - This paper explores the mediating role of post-traumatic stress symptoms in the
      association between sexual abuse and different forms of victimization in dating
      relationships. The study is based on the Quebec Youth Romantic Relationships
      Survey, a survey that explores victimization experiences, including childhood
      sexual abuse, and any emotional, physical, and sexual dating violence in the past
      12 months. The sample involved 8,194 students at 34 secondary schools in Quebec.
      Post-traumatic stress symptoms were evaluated by means of the UCLA PTSD Index. 15
      % of girls and 4 % of boys reported a history of child sexual abuse. Path
      analyses suggest that sexual abuse is positively associated with post-traumatic
      stress symptoms, which in turn are associated with psychological, physical, and
      sexual victimization of dating partners. The study has significant implications
      for prevention of and intervention in dating violence involving victims of sexual
      abuse.

PMID- 29321697
TI  - "We Need to Have a Meeting": Public Housing Demolition and Collective Agency in
      Atlanta, Georgia.
AB  - The last two decades have witnessed widespread demolition of public housing and a
      large-scale relocation of public housing residents. Much of the current
      literature has examined the impact of demolition on relocated residents, focusing
      primarily on individual outcomes such as employment, housing quality, and health.
      This article examines the potential collective consequences of relocation by
      using data from 40 in-depth interviews conducted with relocated public housing
      residents in Atlanta, Georgia, to examine experiences of civic engagement and
      tenant activism before and after relocation. Participants describe frequent
      experiences of civic engagement and tenant activism in their public housing
      communities prior to demolition and also discuss how these collective actions
      often translated into meaningful gains for their communities. Participants also
      describe challenges associated with reestablishing these sources of collective
      agency in their new, post demolition, private-market rental communities where
      opportunities for civic engagement and tenant activism were perceived to be
      limited, where stigma was a barrier to social interaction, and where they
      experienced significant residential instability.

PMID- 29321696
TI  - Security in Father-child Relationship and Behavior Problems in Sexually Abused
      Children.
AB  - While the influence of mother-child relationships on children's recovery
      following sexual abuse has been documented, less is known about the possible
      contribution of father-child relationships on outcomes. The present study
      explored the contribution of children's perception of security in their
      relationship to the father on internalizing and externalizing behavior problems,
      while controlling for sociodemographic variables and variables associated with
      the mother-child relationship. Participants were 142 children who disclosed
      sexual abuse involving a perpetrator other than the biological father. Regression
      analyses indicated that children's perception of security to fathers contributed
      to the prediction of parental reports of children's behavior problems, even after
      controlling for maternal psychological distress and perception of security to
      mothers.

PMID- 29321698
TI  - Reflections on the XVII World Congress of Psychiatry 2017.

PMID- 29321699
TI  - The Association Between Childhood Traumatic Events and Headache-Related
      Parameters in Patients with Migraine: A Cross-Sectional Study in Turkish
      Population.
AB  - Introduction: The aim of this study is to investigate the association between
      childhood traumatic events and headache-related clinical parameters in migraine
      patients. Methods: 95 patients diagnosed with migraine and 50 healthy controls
      were included in the study. A socio-demographic form, the Childhood Trauma
      Questionnaire (CTQ), the Beck Depression Inventory (BDI) and the Beck Anxiety
      Inventory (BAI) were completed by all participants. Additionally, the Visual
      Analog Scale (VAS) and the Migraine Disability Assessment Test (MIDAS) were
      applied to migraine patients. Results: Positive correlations were found between
      emotional abuse, physical abuse, physical neglect, CTQ total scores, and headache
      frequency (r=0.33, r=0.24, r=0.26 and r=0.28 respectively) in migraine patients.
      A positive correlation was found between physical neglect and headache duration
      (r=0.28). Positive correlations were also found between emotional abuse and
      physical neglect, and MIDAS total scores (r=0.22 and r=0.23, respectively).
      Emotional abuse and CTQ total scores were associated with younger mean age of
      headache onset (r=-0.24 and r=-0.23). Conclusion: Childhood traumatic events are
      associated with more frequent and more severe headache episodes, and younger
      headache onset in migraine patients.

PMID- 29321700
TI  - Validation and Reliability Study of the Turkish Version of the Stigma Scale of
      Epilepsy.
AB  - Introduction: We aimed to validate the Turkish version of the Stigma Scale of
      Epilepsy (SSE) (from Brazil) and present the results. Method: The SSE was
      completed by 33 patients with epilepsy (PWE), 25 of the patients' family members,
      and 23 people from the community. Subjects were interviewed on an individual
      basis; a physician read the questions and the subjects wrote the answers on a
      sheet. The form was the same for all subjects. In addition, the Beck Depression
      Inventory (BDI) and the Hamilton Anxiety Inventory (HAI), Short Form-36 (SF-36)
      were completed by the subjects. Results: We interviewed 81 subjects. The internal
      consistency of the SSE showed Cronbach's alpha coefficients of 0.785 for the PWE,
      0.733 for the family members and 0.798 for the people in community. The mean
      scores on the SSE were 57 for patients, 66 for family members and 65 for the
      community where a score of 0 would suggest no stigma and 100 would indicate
      maximum stigma. The SSE scores of patients, family members and the community who
      believed that patients with epilepsy are stigmatized or rejected were higher than
      the SSE scores of who did not believe it. Although there were strong correlation
      between high SSE scores and poor functionality and BDI; there were not any
      correlation between with SSE and HAI, age of epilepsy onset, time of epilepsy,
      education, and social class. Conclusion: The SSE has satisfactory content
      validity and high internal consistency. It allows for the quantification of the
      real perception of the epilepsy associated stigma. Prejudice and discrimination
      are often worse than the seizures themselves in terms of the impact on the daily
      lives of people with epilepsy and their families. Understanding this aspect of
      epilepsy is important for reducing the burden of epilepsy, and the SSE can be
      used for cross cultural, media, and social campaigns aimed at minimizing the
      negative influences of stigma.

PMID- 29321701
TI  - Psychotherapy: Playing the Three Monkeys in Mental Health Service Provision?
AB  - Introduction: The purpose of the present study was to investigate the effect of
      sociodemographic variables on the knowledge of, demand for, and reception of
      psychotherapy as a treatment modality among psychiatric outpatients. Methods:
      Participants of the study were 240 psychiatric outpatients (170 females and 70
      males). Data for mental health services were collected from a subgroup of 103
      "experienced" patients (42.9%) having had received psychiatric help previously.
      All participants were administered a questionnaire containing questions about
      various forms of psychiatric services. Results: Of all participants, 40.83%
      reported having heard of psychotherapy a few of times before, mostly (44.58%)
      from the media and only 3.33% from a mental health professional. Most
      participants with previous applications to psychiatric outpatient clinic had
      first received mental health service from a psychiatrist (93.2%) and at a state
      hospital (72.8%), and a small minority (17.4%) had subsequently received care
      from a psychologist. None had demanded to, but 5 patients (4.86%) had been
      recommended to receive psychotherapy by mental health professionals. Of these
      experienced patients, 20 (19.41%) have an idea that the interviews they had
      previously at the outpatient clinics were sort of psychotherapeutic interviews;
      yet, only 7 (6.79%) retained the same idea after reading the definition of
      appropriate psychotherapy written on the questionnaire. All of these patients
      declared that they have received both their medication and psychotherapy at the
      same time. Thus, only 2.91% of 240 participants received psychotherapy that
      corresponds to the given definition. Conclusions: Findings from this study
      suggest that mental health care is mostly performed by psychiatrists alone, with
      a limited contribution by psychologists. Consequently, the choice of treatment is
      solely pharmacotherapy for most patients, while psychotherapy as a treatment
      modality is neither offered nor demanded in routine practice.

PMID- 29321702
TI  - Carpal Tunnel Syndrome in Obstructive Sleep Apnea Patients.
AB  - Introduction: Carpal tunnel syndrome (CTS) is the most common entrapment
      neuropathy of the upper extremity. It is usually associated with the compression
      of the median nerve in the median groove. Because the main symptoms of CTS pain
      and numbness worsen at night, sleep disorders in CTS patients and the impact of
      preferred sleeping position on CTS development have been formerly studied.
      However, to the best of our knowledge, this is the first study assessing the
      frequency of CTS in obstructive sleep apnea (OSA) patients. This study aimed to
      determine the frequency of CTS in OSA patients and evaluate the causative
      relation between the two diseases. Methods: Records of individuals who were
      admitted to our sleep laboratory were retrospectively scanned. Eighty patients
      who were diagnosed with OSA and did not have comorbidities that might cause OSA
      (e.g., diabetes mellitus, hypothyroiditis, rheumatic diseases, and cervical
      radiculopathy) were included in the study along with 80 healthy controls who
      matched for age, sex, and BMI of OSA patients. To maintain observer blindness,
      patients were not questioned regarding their symptoms or the clinical data that
      would be used in the study. All participants underwent nerve conduction studies.
      Those who were diagnosed with CTS were questioned regarding CTS symptoms and the
      preferred sleeping position. Subsequently, patients were given the Boston CTS
      questionnaire. Results: CTS frequency in OSA patients was found to be 27.5%.
      There was no significant relation between preferred sleeping position or being a
      manual worker and having CTS. Conclusion: CTS frequency in OSA patients is
      significantly higher than that in healthy individuals. In contrast to previous
      studies that have been performed in the absence of polysomnographic and
      electrophysiological data, in our study biomechanical factors were not associated
      with CTS presence. Therefore, we conclude that intermittent hypoxemia is the main
      etiological factor for CTS in OSA patients. Inflammation may be a common factor
      for etiopathogenesis for both diseases, but this hypothesis needs further
      investigation.

PMID- 29321703
TI  - Executive Functions of Obsessive Compulsive Disorder and Panic Disorder Patients
      in Comparison to Healty Controls.
AB  - Introduction: Patients with obsessive compulsive disorder (OCD) have impaired
      cognitive functions, including attention, verbal and visual memory, and visual
      spatial abilities as well as executive function But some studies did not show any
      disturbance in executive function of patients with OCD. To date, only few studies
      have been conducted on neuropsychological functioning of patients with panic
      disorder (PD). There are limited studies to reach a definite conclusion on
      executive functions of patients with OCD and those with PD. In this study, we
      aimed to measure executive functions of patients with OCD and those with PD
      compared with those of healthy controls. Although there are many studies on
      cognitive functions of patients with OCD, there appears to be no consistency in
      results and no findings have been obtained to enable us to reach definite
      conclusions. Although there are very few studies on neuropsychological functions
      of patients with PD, impairments on a set of cognitive functions have been
      demonstrated. To date, no finding with respect to impairment in executive
      functions of patients with PD has been published. PD and OCD are disorders
      manifesting similar characteristics, with the presence of anxiety and avoidance
      behavior. Besides this, patients with OCD also have symptoms such as obsessions
      and compulsions that are characteristics of this disorder. We aim to compare
      executive functions in the three groups (patients with OCD, those with PD, and
      healthy controls) in this study. Method: Seventeen patients with OCD and 15
      patients with PD who were diagnosed according to Diagnostic and Statistical
      Manual of Mental Disorder -IV-TR (DSM-IV-TR) and 26 healthy control subjects were
      included in this study. Patients who used medication as well as those with
      medical illnesses and Axis-I comorbidities were excluded. The healthy control
      group subjects were matched with the patients in terms of age, gender, and
      education. Structured Clinical Interview for DSM-IV Axis-I Disorders-Clinical
      Version (SCID-I), Hamilton Depression Rating Scale (HDRS), and Yale-Brown
      obsessive compulsive scale tests (Y-BOCS) were administered to the patients.
      Trail Making Tests (TMT), verbal fluency tests (Controlled Oral Word Association
      Test and Categorical Naming), Stroop Test, and Wisconsin Card Sorting Test (WCST)
      were administered to the study groups. Results: According to our results, there
      was no statistically significant difference between the three study groups with
      respect to executive functions. There was also no significant correlation between
      executive tests' results and Y-BOCS'in the OCD group. Conclusion: The results of
      the PD group are in line with that reported in literature. The results of the OCD
      group can be explained by a lack of medication usage and any comorbidity
      including depression. A small sample size is the major limitation of our study.

PMID- 29321704
TI  - Efficacy and Safety of Warfarin Experience in a Stroke Polyclinic in Stroke
      Patients.
AB  - Introduction: Cardioembolic stroke is associated with high morbidity and
      mortality, with an increased risk of recurrent stroke. Oral anticoagulation is
      highly effective in reducing the risk of stroke and mortality compared with
      placebo. Our study aimed to highlight the safety and efficacy of warfarin by
      analyzing the 20-year follow-up of patients on warfarin therapy. Methods: A
      retrospective observational study was performed with ischemic stroke patients
      receiving warfarin at our stroke polyclinic between 1992 and 2012. The CHADS2
      scoring system was used to assess the annual risk of stroke, and a bleeding risk
      score termed the HAS-BLED scoring system was calculated to estimate the risk of
      bleeding. Results: In our study, 394 patients who were receiving warfarin therapy
      were included. The patients' median age was 66.35+/-13.602 years. The median
      follow-up period of the patients was 4.85+/-3.572 years. During follow-up, 79.9%
      of the patients revealed no complication on warfarin therapy. Thirty-seven
      patients had hemorrhagic complications; among these, 33 had systemic
      complications (including nose bleeding, hematuria, hematochezia) and 4 patients
      had intracerebral bleeding. The INR value related to hemorrhagic complications
      was >2.5 in 75.8% of 33 patients having systemic bleeding and in 75% of 4
      patients having intracerebral bleeding. The HAS-BLED risk score was >3 in 72.7%
      of the patients experiencing systemic bleeding complications. Forty-one patients
      had a recurrent ischemic stroke/TIA during the follow-up. Of this patient group,
      the INR value at the time of recurrent ischemic stroke was <2 in 41 patients
      (92.7%), while the CHADS2 risk score was low in this group. Sixty-eight patients
      were receiving antiplatelet therapy with warfarin. In these groups, 16 patients
      experienced a complication during the follow-up (bleeding/ischemic), while 10
      patients had bleeding complications (systemic and intracerebral). Conclusion: The
      results suggest that the effectiveness and safety of warfarin depend on
      maintaining its dose at sufficient levels to keep the patient's INR within the
      therapeutic range.

PMID- 29321705
TI  - Attention-Deficit/Hyperactivity Disorder and Nicotine Dependence in Adults.
AB  - Introduction: The aim of this study is to assess clinical characteristics and
      smoking profiles of individuals diagnosed with attention-deficit/hyperactivity
      disorder (ADHD) and compare their nicotine dependence status with healthy
      controls for better understanding the mutual and complex relationship between
      ADHD and smoking. Methods: We included the following participants in the study:
      40 adults with the diagnosis of ADHD, 40 participants who visited the smoking
      cessation polyclinic without any psychiatric disorders, and 40 healthy controls.
      A sociodemographic data form, Wender Utah Rating Scale (WURS), Adult ADD/ADHD
      Diagnosis and Evaluation Inventory, and Fagerstrom Nicotine Dependence Test
      (FNDT) were administered to the participants. Results: Mean age of the ADHD,
      nicotine dependence, and control groups was 28.68+/-7.22, 34.17+/-8.60, 33.70+/
      7.45 years, respectively. Percentages of females and males were 27.5% and 72.5%
      in the ADHD group, 50% and 50% in the nicotine dependence group, 47.5% and 52.5%
      in the control group. The attention-deficit scores in the ADHD, nicotine
      dependence, and control groups were 21.18+/-5.05, 7.23+/-3.96, 4.75+/-2.65,
      respectively (p=0.001), whereas the hyperactivity scores were.73+/-5.84, 6.43+/
      4.2, and 3.58+/-2.27, respectively (p=0.001). The related features scores were
      56.53+/-12.96, 24.30+/-13.93, and 13.13+/-6.11, respectively (p=0.001), whereas
      the WURS scores were 61.88+/-12.69, 23.03+/-16.07, 11.90+/-8.15, respectively
      (p=0.001). FNDT scores in ADHD and nicotine dependence groups were 5.83+/-2.11
      and 6.20+/-2.74, respectively (p=0.495). Conclusion: Considering the argument of
      ADHD being an independent risk factor for nicotine dependence, we think the co
      occurrence of the smoking addiction and ADHD symptoms in the context of dopamine
      dysregulation is important in the clinical setting. Treatment modalities and of
      preventive strategies should be considered while keeping this in mind.

PMID- 29321706
TI  - Validity and Reliability of the Turkish Version of the Multiple Sclerosis-Related
      Symptom Checklist.
AB  - Introduction: Multiple sclerosis (MS) is a disease that causes different symptoms
      in each attack and has an individual-specific course. Detailed questioning and
      recording of MS symptoms is important for developing a management plan for
      individual-specific symptoms. The present study was planned to evaluate the
      validity and reliability of the Turkish version of "Multiple Sclerosis-Related
      Symptom Checklist" (MS-RS), which has been developed for patients to personally
      follow-up the symptoms they experience. Methods: The study was conducted in the
      outpatient MS clinic of the Istanbul University Istanbul Faculty of Medicine
      between January and October 2013 and included a sample group of 148 patients who
      were aged >18 years, could easily communicate, had a definite diagnosis of MS,
      and had no other medical problems besides MS. The data were collected using
      patient information forms, including sociodemographic and MS-RS forms. To assess
      the linguistic validity, the Likert-type scale with 26 items was first applied to
      a group of 30 patients. Confirmatory factor analysis was used to test the
      construct validity. Furthermore, the correlation of the scale with the Expanded
      Disability Status Scale (EDSS), Hospital Anxiety and Depression Scale (HADS),
      Mini-Mental Status Evaluation (MMSE) scale, and Multiple Sclerosis Quality of
      Life Scale-54 (MSQL-54) was evaluated. Results: The scale comprised five factors
      with factor loading values between 0.39 and 0.86. The item-total correlation
      coefficients revealed values of 0.27-0.88. The Cronbach's alpha reliability
      coefficient for the whole scale was determined to be 0.89 and for the subscales
      to be 0.60-0.85. The test-retest analysis revealed no difference between the
      scale and its subscales in terms of invariance with time (p>0.05). Moreover, MS
      RS was significantly correlated with EDSS, HADS, MMSE, and MSQL-54. Conclusion:
      The Turkish version of MS-RS is a valid and reliable scale that can be used in
      the Turkish population.

PMID- 29321707
TI  - Validity and Reliability of the Turkish Version for DSM-5 Level 2 Anger Scale
      (Child Form for Children Aged 11-17 Years and Parent Form for Children Aged 6-17
      Years).
AB  - Introduction: This study aimed to assess the validity and reliability of the
      Turkish version of Diagnostic and Statistical Manual of Mental Disorders (DSM-5)
      Level 2 Anger Scale. Methods: The scale was prepared by translation and back
      translation of DSM-5 Level 2 Anger Scale. Study groups consisted of a clinical
      sample of cases diagnosed with depressive disorder and treated in a child and
      adolescent psychiatry unit and a community sample. The study was continued with
      218 children and 160 parents. In the assessment process, child and parent forms
      of DSM-5 Level 2 Anger Scale and Children's Depression Inventory and Strengths
      and Difficulties Questionnaire-Parent Form were used. Results: In the reliability
      analyses, the Cronbach alpha internal consistency coefficient values were found
      very high regarding child and parent forms. Item-total score correlation
      coefficients were high and very high, respectively, for child and parent forms
      indicating a statistical significance. As for construct validity, one factor was
      maintained for each form and was found to be consistent with the original form of
      the scale. As for concurrent validity, the child form of the scale showed
      significant correlation with Children's Depression Inventory, while the parent
      form showed significant correlation with Strengths and Difficulties Questionnaire
      Parent Form. Conclusion: It was found that the Turkish version of DSM-5 Level 2
      Anger Scale could be utilized as a valid and reliable tool both in clinical
      practice and for research purposes.

PMID- 29321709
TI  - The Probable Prevalence and Sociodemographic Characteristics of Specific Learning
      Disorder in Primary School Children in Edirne.
AB  - Introduction: The aim of this study was to research the probable prevalence of
      Specific Learning Disorder (SLD) in primary school children in Edirne City and
      the relationships with their sociodemographic characteristics. Methods: The
      sample of our study was composed of 2,174 children who were educated in primary
      schools in second, third, and fourth grades in the academic year 2013-2014 in
      Edirne City. The teachers and parents of these children were given Specific
      Learning Difficulties Symptom Scale, Learning Disabilities Symptoms Checklist
      (teacher and parent forms), and sociodemographic data forms to fill in. Binary
      logistic regression analysis was used to assess the risk factors for SLD.
      Results: Our study revealed that the probable prevalence of SLD was 13.6%; 17%
      for boys and 10.4% for girls. Reading impairment was 3.6%, writing impairment was
      6.9%, and mathematic impairment was 6.5%. We determined that consanguineous
      marriages, low income, history of neonatal jaundice were found as risks for SLD;
      born by caesarean, developmental delay of walking, and history of neonatal
      jaundice were found as risks for mathematic impairment. A history of learning
      difficulties of parents was a risk factor for forming SLD and subtypes.
      Conclusion: Our findings were consistent with other study results about the
      prevalence of SLD. The relationships between the probable prevalence rates and
      sociodemographic data were discussed.

PMID- 29321708
TI  - Holter Monitorisation Results in Early Period of Acute Ischemic Stroke.
AB  - Introduction: Paroxysmal atrial fibrillation (PAF) has a similar risk with
      persistent AF for ischemic stroke. Holter monitorization (HM) and other long-term
      monitorization methods increased the detection of PAF and short-lasting runs of
      tachyarrhythmias. Their classification as PAF and roles in the etiology of
      ischemic stroke is controversial. In this study, we aimed to investigate the
      frequency of any duration of PAF and clinical characteristics of the patients
      with acute ischemic stroke who have undergone 24-hrs HM. Methods: Patients with
      acute ischemic stroke and transient ischemic attack (TIA) hospitalized in the
      Neurology ward and undergone 24-hrs of HM during their hospital stay were
      included in the study. HM reports, clinical, and laboratory characteristics were
      analyzed, retrospectively. Patients were grouped into three based on HM: 1st
      group, without PAF; 2nd group, PAF >30 seconds (s) and 3rd group, PAF<30s.
      Results: PAF of any duration was detected in 18.8% (n=49) of 261 patients. The
      duration of PAF was <30s in 16.1% (n=42) and >30s in 2.7% (n=7) of the patients.
      The mean age, left atrium diameter and CHA2DS2-VASc scores of the second group
      were significantly higher than the first group (p<0.001, p<0.001 and p=0.007;
      respectively). The mean age, left atrium diameter, modified Rankin Scores (mRS),
      and CHA2DS2-VASc scores of the third group were significantly higher than the
      first group (p<0.001; for all). There was no difference between the second and
      the third groups in means of mean age, left atrial diameter, MRS, and CHA2DS2
      VASc scores (p<0.017, for all). Conclusion: In this study, 24-hrs HM in the early
      period of acute ischemic stroke results yielded a high frequency of PAF<30s and
      predictive features were in parallel with the literature.

PMID- 29321710
TI  - Cytokine Polymorphism and HLA Genotyping in Patients with Temporal Lobe Epilepsy
      Related to Hippocampal Sclerosis.
AB  - Objective: Hippocampal sclerosis (HS) is the most common pathological substrate
      associated with mesial temporal lobe epilepsy (MTLE), where inflammatory
      processes are known to play an increasingly important role in the pathogenesis.
      To further investigate the role of the immune system, both cytokine gene
      polymorphisms and human leukocyte antigen (HLA) genotyping in patients with MTLE
      HS were investigated. Methods: The DNA samples of 100 patients with MTLE-HS and
      201 healthy individuals were genotyped for cytokines (IL-6,IL-10, TNF-alpha, TGF
      beta1 and IFN-gamma) and HLA using polymerase chain reaction (PCR)-SSP and SSO
      methods. The results were statistically analyzed in patient and healthy control
      groups and then according to the presence of febrile seizures (FS) in the patient
      group. Results: Analysis of cytokine genotyping did not reveal any significant
      difference between patients with MTLE-HS and controls and patients with or
      without FS. However, the HLA DRB1*13 allele was found to be more frequent in the
      patient population after Bonferroni correction. Conclusion: This study suggests
      the possible role of HLA in the pathogenesis of MTLE-HS, although it failed to
      show any relationship with the cytokine system. However, data regarding the role
      of HLA are still lacking, and further studies are necessary to verify our
      results.

PMID- 29321711
TI  - Validity and Reliability of the Turkish version of DSM-5 Social Anxiety Disorder
      Severity Scale- Child Form.
AB  - Introduction: This study aimed to assess the validity and reliability of the
      Turkish version of the Diagnostic and statistical manual of Mental Disorders.
      (5th ed.) (DSM-5) Social Anxiety Disorder Severity Scale- Child Form. Method: The
      scale was prepared by carrying out the translation and back translation of the
      DSM-5 Social Anxiety Disorder Severity Scale - Child Form. The study group
      consisted of 31 patients that had been treated in a child psychiatry unit and
      diagnosed with social anxiety disorder and 99 healthy volunteers that were
      attending middle or high school during the study period. For the assessment, the
      Screen for Child Anxiety and Related Emotional Disorders (SCARED) was also used
      along with the DSM-5 Social Anxiety Disorder Severity Scale - Child Form.
      Results: Regarding reliability analyses, Cronbach's alpha internal consistency
      coefficient was calculated as 0.941, while item-total score correlation
      coefficients were measured between 0.566 and 0.866. A test-retest correlation
      coefficient was calculated as r=0.711. As for construct validity, one factor that
      could explain 66.0 % of the variance was obtained. As for concurrent validity,
      the scale showed a high correlation with the SCARED. Conclusion: It was concluded
      that the Turkish version of the DSM-5 Social Anxiety Disorder Severity Scale -
      Child Form could be utilized as a valid and reliable tool both in clinical
      practice and for research purposes.

PMID- 29321713
TI  - Two Branches of the Same Tree: A Brief History of Turkish Neuropsychiatric
      Society (1914-2016).
AB  - Introduction: The aim of this article is to provide a brief history of Turkish
      Neuropsychiatric Society by examining its institutional background, the
      milestones within its history, and the major activities undertaken by the
      organization during the years. Methods: Firstly, the books, journals, and
      articles that are related to the history of psychiatry and neurology in Turkey
      have been reviewed and the information that can explain the history of the
      society has been brought together. The founding records, regulations, journals,
      and congress booklets of Tababet-i Akliye ve Asabiye Cemiyeti (Society of
      Psychiatry and Neurology) have been examined and the newspapers of the period
      have been reviewed to collect news concerning congresses and meetings. Besides,
      oral history interviews have been conducted with regard to the recent history of
      the society. Results: Although the roots of neuropsychiatry in Turkey date back
      to the mid-nineteenth century, the first society, which was called Tababet-i
      Akliye ve Asabiye Cemiyeti (Society of Psychiatry and Neurology), was founded in
      1914. The organization now maintains its activities under the name Turk
      Noropsikiyatri Dernegi (Turkish Neuropsychiatric Society). Turkish
      Neuropsychiatric Society has organized monthly meetings, conferences, and
      national congresses and has published numerous scientific journals in the field
      of neuropsychiatry over the past century. Conclusion: As one of the earliest
      societies of medical specialty in Turkey, Turkish Neuropsychiatric Society has
      played a crucial role in the development and institutionalization of psychiatry
      and neurology. The administration and activities of the society occurred in the
      following institutions respectively: Toptasi Asylum (1914-1925), Bakirkoy (1925
      1955), and Capa (Psychiatry Clinic of Medical Faculty of Istanbul University).
      The society was mainly composed of psychiatrists and neurologists; however,
      neurosurgeons, psychologists, and neuropsychologists also attended the congresses
      and meetings held by the group.

PMID- 29321712
TI  - Sensorimotor Integration During Motor Learning: Transcranial Magnetic Stimulation
      Studies.
AB  - The effect of sensory signals coming from skin and muscle afferents on the
      sensorimotor cortical networks is entitled as sensory-motor integration (SMI).
      SMI can be studied electrophysiologically by the motor cortex excitability
      changes in response to peripheral sensory stimulation. These changes include the
      periods of short afferent inhibition (SAI), afferent facilitation (AF), and late
      afferent inhibition (LAI). During the early period of motor skill acquisition,
      motor cortex excitability increases and changes occur in the area covered by the
      relevant zone of the motor cortex. In the late period, these give place to the
      morphological changes, such as synaptogenesis. SAI decreases during learning the
      motor skills, while LAI increases during motor activity. In this review, the role
      of SMI in the process of motor learning and transcranial magnetic stimulation
      techniques performed for studying SMI is summarized.

PMID- 29321714
TI  - Cavum Vergae, Liability, and Steroid Treatment: Manic Episode, Brain Imaging
      Findings, and Clinical Follow-up of a Systemic Lupus Erythematosus Case.
AB  - Systemic lupus erythematosus (SLE) or Lupus is a chronic and idiopathic
      autoimmune connective tissue disease that involves several organs and organ
      systems. SLE may lead to a group of psychiatric manifestations, including
      delirium, anxiety disorders, cognitive dysfunction, mood disorders, and
      psychosis, which are caused by organic or non-organic factors. In addition, it is
      thought that the most common cause of neuropsychiatric lupus is corticosteroid
      use; central nervous system involvement and inflammatory processes also have an
      important role in the development of psychiatric manifestations. In other
      respects, structural brain abnormalities induce proneness to psychotic and manic
      symptoms. Along with this proneness, cavum vergae, an anomaly closely related to
      the anatomic areas associated with mood regulation, may precipitate manic
      symptoms. In this case report, we present a manic episode case emerging after
      delirium, with a 1-year history of SLE, which has recently been diagnosed with
      cavum vergae and discuss the process of infection and corticosteroid treatment,
      which contributed to the proneness effect of a structural brain anomaly.

PMID- 29321715
TI  - A Patient with Neuro-Behcet's Syndrome Presenting with Peripheral Nerve
      Involvement.

PMID- 29321717
TI  - Engaging Canadian First Nations Women in Cervical Screening through Education.
AB  - Recognition of the need to decrease cervical cancer rates in Indigenous
      populations has been ongoing-yet few successful interventions have been reported.
      In addition, literature addressing the challenges and barriers associated with
      designing screening programs aimed to specifically reach Indigenous women is
      limited. Here, we report findings from a mixed methods cervical cancer research
      project conducted in partnership with 10 First Nations communities in northwest
      Ontario, Canada. Individual interviews with community health professionals (the
      majority of whom identified as First Nations) stressed that awareness of cervical
      screening benefits is lacking. In contrast, focus group participants (women with
      no formal health education) emphasized the desire to learn more about the science
      of human papillomavirus (HPV), and that a positive HPV or abnormal Papanicolaou
      test need not mean a woman will undoubtedly develop cervical cancer. Both the
      health professionals and the focus group participants highlighted that sexual
      health education must start early, in schools, preferably before girls are
      sexually active and that it has to continue throughout life to create a screening
      culture with a focus on women's wellbeing. Both interview and focus group
      participants highlighted that sexual health education must start early, in
      schools, preferably before girls are sexually active and that it has to continue
      throughout life to create a screening culture with a focus on women's wellbeing.
      Health professionals elaborated mainly on special events for community women
      whereas focus group participants also recognized the need to include community
      men in health education particularly for de-stigmatizing the sexually-transmitted
      HPV infection.

PMID- 29321718
TI  - A novel Notch1 missense mutation (C1133Y) in the Abruptex domain exhibits
      enhanced proliferation and invasion in oral squamous cell carcinoma.
AB  - Background: Notch1 has been regarded as a fundamental regulator in tissue
      differentiation and stem cell properties. Recently, Notch1 mutations have been
      reported intensively both in solid tumors and in hematopoietic malignancies.
      However, little is known about the biological effect and the clinical implication
      of these reported mutations. Previously, we discovered several missense mutations
      in the Notch1 receptor in a Chinese population with oral squamous cell carcinoma
      (OSCC). Methods: We selected a 'hotspot' mutation in the Abruptex domain
      (C1133Y). The expression of Notch1 was determined by western blot and real-time
      qPCR in OSCC cell lines transfected with pcDNA3.1-Notch1WT, pcDNA3.1
      Notch1C1133Y, or pcDNA3.1 empty vector. CCK-8 assays were used to assess cell
      proliferation. Flow cytometry and western blot were used to confirm the
      alteration of cell cycle after transfection. Transwell assays and the detection
      of Epithelial-to-mesenchymal transition (EMT) markers were used to determine the
      invasive ability. The effects of Notch1 C1133Y mutation were analyzed by
      Immunofluorescence staining and the expression of EGFR-PI3K/AKT signaling.
      Results: We demonstrated that Notch1C1133Y mutation inactivated the canonical
      Notch1 signaling. We identified an oncogenic phenotype of this mutation by
      promoting cell proliferation, invasion and by inducing EMT in OSCC cell lines. We
      found that the Notch1C1133Y mutation exhibited a decreased S1-cleavage due to the
      impaired transport of Notch1 protein from the endoplasmic reticulum (ER) to the
      Golgi complex, which was consistent with the observation of the failure of the
      Notch1C1133Y mutated receptor to present at the cell surface. Importantly, the
      mutated Notch1 activated the EGFR-PI3K/AKT signaling pathway, which has been
      confirmed as an overwhelming modulator in OSCC. Conclusions: Taken together, our
      findings revealed for the first time a novel Notch1 mutation that enhances
      proliferation and invasion in OSCC cell lines. The Notch1 C1133Y mutation impairs
      the processing of notch1 protein and the critical links between the mutated
      Notch1 and the activated EGFR-PI3K/AKT signaling pathway.

PMID- 29321720
TI  - Prevalence of Pregnancy Involvement Among Canadian Transgender Youth and its
      Relation to Mental Health, Sexual Health, and Gender Identity.
AB  - While little research has been conducted into the reproductive experiences of
      transgender people, available evidence suggests that like cisgender people, most
      transgender people endorse a desire for these experiences. This study explores
      the pregnancy experiences and related health factors among transgender and gender
      diverse 14-25 year olds using a national Canadian sample (N = 923). Results
      indicated that 26 (5%) transgender youth reported a pregnancy experience in the
      past and the prevalence among 14-18 year olds was comparable to population-based
      estimates using the same question in the British Columbia Adolescent Health
      Survey. Transgender youth with a history of pregnancy involvement reported a
      diverse range of gender identities, and this group did not differ from the
      remainder of the sample on general mental health, social supports, and living in
      felt gender. This group did report over six times greater likelihood of having
      been diagnosed with a sexually transmitted infection by a doctor (19%), but did
      they not differ in reported contraception use during last sexual intercourse.
      These findings suggest that pregnancy involvement is an issue that should not be
      overlooked by health professionals working with transgender youth and that this
      group has particular sexual health needs.

PMID- 29321719
TI  - Cancer chemoprevention and therapy using chinese herbal medicine.
AB  - Traditional Chinese medicine (TCM) plays an indispensable role in cancer
      prevention and treatment. Chinese herbal medicine (CHM) is a key component of TCM
      and has been practiced for thousands of years. A number of naturally occurring
      products from Chinese herbs extracts exhibit strong inhibitory properties against
      carcinogenesis, including CHM single-herb extracts, CHM-derived active
      components, and CHM formulas (the polyherbal combinations), which regulate
      JAK/STAT, MAPK, and NF-?B pathways. The present review aims to report the cancer
      preventive effect of CHM with evidence from cell-line, animal, epidemiological,
      and clinical experiments. We also present several issues that have yet to be
      resolved. In the future, cancer prevention by CHM will face unprecedented
      opportunities and challenges.

PMID- 29321721
TI  - Antigen 85B peptidomic analysis allows species-specific mycobacterial
      identification.
AB  - Background: Nontuberculous mycobacteria (NTM)-mediated infections are a growing
      cause of worldwide morbidity, but lack of rapid diagnostics for specific NTM
      species can delay the initiation of appropriate treatment regimens. We thus
      examined whether mass spectrometry analysis of an abundantly secreted
      mycobacterial antigen could identify specific NTM species. Methods: We analyzed
      predicted tryptic peptides of the major mycobacterial antigen Ag85B for their
      capacity to distinguish Mycobacterium tuberculosis and three NTM species
      responsible for the majority of pulmonary infections caused by slow-growing
      mycobacterial species. Next, we analyzed trypsin-digested culture supernatants of
      these four mycobacterial species by liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) to detect candidate species-specific Ag85B peptides, the
      identity of which were validated by LC-MS/MS performed in parallel reaction
      monitoring mode. Results: Theoretical tryptic digests of the Ag85B proteins of
      four common mycobacterial species produced peptides with distinct sequences,
      including two peptides that could each identify the species origin of each Ag85B
      protein. LC-MS/MS analysis of trypsinized culture supernatants of these four
      species detected one of these species-specific signature peptides in each sample.
      Subsequent LC-MS/MS analyses confirmed these results by targeting these species
      specific Ag85B peptides. Conclusions: LC-MS/MS analysis of Ag85B peptides from
      trypsin-digested mycobacterial culture supernatants can rapidly detect and
      identify common mycobacteria responsible for most pulmonary infections caused by
      slow-growing mycobacteria, and has the potential to rapidly diagnose pulmonary
      infections caused by these mycobacteria through direct analysis of clinical
      specimens.

PMID- 29321722
TI  - Distinct virulent network between healthcare- and community-associated
      Staphylococcus aureus based on proteomic analysis.
AB  - Background: Staphylococcus aureus (S. aureus or SA) is a leading cause of
      healthcare-associated (HA-) and community-associated (CA) infection. HA-SA
      isolates usually cause nosocomial pneumonia, bloodstream infections, catheter
      related urinary tract infections, etc. On the other hand, CA-SA isolates usually
      cause highly fatal diseases, such as SSTIs as well as post influenza necrotic
      hemorrhagic pneumonia. The differences of the infection types are partially due
      to the unique characteristics between HA-SA and CA-SA isolates. For example, HA
      SA isolates showed strong adherence to host epithelial cells, while CA-SA
      isolates displayed higher virulence due to the increased activity of the
      important quorum-sensing system accessory gene regulator (agr). Thus, the aim of
      this study was to characterize the proteomic difference between HA-SA and CA-SA
      lineage. Methods: In this study, the extracted peptides from those representative
      strains were analyzed by LC-MS/MS. The protein-protein interaction network was
      constructed by bioinformatics and their expressions were verified by RT-PCR and
      Western blot. Results: We demonstrated that Agr system (AgrA and AgrC) and its
      interactive factors (PhoP, SrrB, YycG, SarX, SigB and ClpP) based on the protein
      protein interaction network were expressed significantly higher in the epidemic
      Chinese CA-SA lineage ST398 compared to HA-SA lineage ST239 by LC-MS/MS. We
      further verified the increased transcription of all these genes in ST398 by RT
      PCR, suggesting that the higher expression of these genes/proteins probably play
      role in the acute infection of CA-SA. Moreover, surface-related proteins (FnbpA,
      SpA, Atl, ClfA, IsaA, IsaB, LtaS, SsaA and Cna) that are repressed by the Agr
      system have significantly higher expression in the epidemic Chinese HA-SA clone
      ST239 in comparison to CA-SA lineage ST398 by LC-MS/MS. Furthermore, we confirmed
      the significantly increased expression of two important adhesive proteins (Atl
      and ClfA) in ST239 by Western blot, which may contribute to the durative
      infection of HA-SA. Conclusion: The results suggest that the different proteomic
      profile, at least partially, contribute to the pathogenic differences between HA
      SA and CA-SA.

PMID- 29321724
TI  - Netrin-1 Prevents Rat Primary Cortical Neurons from Apoptosis via the DCC/ERK
      Pathway.
AB  - In the nervous system, Netrin-1 serves as a neural guide, mediating the neuronal
      development. However, it remains blurred whether Netrin-1 can protect neurons
      from apoptosis induced by cerebral stroke. In the current study, the cultured rat
      primary cortical neurons were transfected with Netrin-1-encoding lentivirus
      before the oxygen-glucose-deprivation (OGD) treatment. Cell death and apoptosis
      were evaluated by lactate dehydrogenase (LDH) release and flow cytometry. We
      found that Netrin-1 attenuated OGD-induced cell death and neuronal apoptosis at
      24 h after OGD treatment, and that the overexpression of Netrin-1 activated the
      ERK signaling pathway. These effects were partly abolished by blocking its
      receptor deleted in colorectal cancer (DCC) or U0126, an inhibitor of the ERK
      signaling pathway. Netrin-1 overexpression in neurons elevated the expression of
      DCC, on mRNA level and protein level. Netrin-1 also reduced DNA damage. Taken
      together, our findings suggest that Netrin-1 attenuates cell death and neuronal
      apoptosis via the DCC/ERK signaling pathway in the cultured primary cortical
      neurons after OGD injury, which may involve the mediation of DNA damage in the
      neurons.

PMID- 29321723
TI  - Remodeling Functional Connectivity in Multiple Sclerosis: A Challenging
      Therapeutic Approach.
AB  - Neurons in the central nervous system are organized in functional units
      interconnected to form complex networks. Acute and chronic brain damage disrupts
      brain connectivity producing neurological signs and/or symptoms. In several
      neurological diseases, particularly in Multiple Sclerosis (MS), structural
      imaging studies cannot always demonstrate a clear association between lesion site
      and clinical disability, originating the "clinico-radiological paradox." The
      discrepancy between structural damage and disability can be explained by a
      complex network perspective. Both brain networks architecture and synaptic
      plasticity may play important roles in modulating brain networks efficiency after
      brain damage. In particular, long-term potentiation (LTP) may occur in surviving
      neurons to compensate network disconnection. In MS, inflammatory cytokines
      dramatically interfere with synaptic transmission and plasticity. Importantly, in
      addition to acute and chronic structural damage, inflammation could contribute to
      reduce brain networks efficiency in MS leading to worse clinical recovery after a
      relapse and worse disease progression. These evidence suggest that removing
      inflammation should represent the main therapeutic target in MS; moreover, as
      synaptic plasticity is particularly altered by inflammation, specific strategies
      aimed at promoting LTP mechanisms could be effective for enhancing clinical
      recovery. Modulation of plasticity with different non-invasive brain stimulation
      (NIBS) techniques has been used to promote recovery of MS symptoms. Better
      knowledge of features inducing brain disconnection in MS is crucial to design
      specific strategies to promote recovery and use NIBS with an increasingly
      tailored approach.

PMID- 29321725
TI  - alpha-Synuclein Dimers Impair Vesicle Fission during Clathrin-Mediated Synaptic
      Vesicle Recycling.
AB  - alpha-Synuclein is a presynaptic protein that regulates synaptic vesicle (SV)
      trafficking. In Parkinson's disease (PD) and several other neurodegenerative
      disorders, aberrant oligomerization and aggregation of alpha-synuclein lead to
      synaptic dysfunction and neurotoxicity. Despite evidence that alpha-synuclein
      oligomers are generated within neurons under physiological conditions, and that
      altering the balance of monomers and oligomers contributes to disease
      pathogenesis, how each molecular species of alpha-synuclein impacts SV
      trafficking is currently unknown. To address this, we have taken advantage of
      lamprey giant reticulospinal (RS) synapses, which are accessible to acute
      perturbations via axonal microinjection of recombinant proteins. We previously
      reported that acute introduction of monomeric alpha-synuclein inhibited SV
      recycling, including effects on the clathrin pathway. Here, we report the effects
      of alpha-synuclein dimers at synapses. Similar to monomeric alpha-synuclein, both
      recombinant alpha-synuclein dimers that were evaluated bound to small liposomes
      containing anionic lipids in vitro, but with reduced efficacy. When introduced to
      synapses, the alpha-synuclein dimers also induced SV recycling defects, which
      included a build up of clathrin-coated pits (CCPs) with constricted necks that
      were still attached to the plasma membrane, a phenotype indicative of a vesicle
      fission defect. Interestingly, both alpha-synuclein dimers induced longer necks
      on CCPs as well as complex, branching membrane tubules, which were distinct from
      the CCPs induced by a dynamin inhibitor, Dynasore. In contrast, monomeric alpha
      synuclein induced a buildup of free clathrin-coated vesicles (CCVs), indicating
      an inhibition of clathrin-mediated endocytosis at a later stage during the
      clathrin uncoating process. Taken together, these data further support the
      conclusion that excess alpha-synuclein impairs SV recycling. The data
      additionally reveal that monomeric and dimeric alpha-synuclein produce distinct
      effects on clathrin-mediated endocytosis, predicting different molecular
      mechanisms. Understanding what these mechanisms are could help to further
      elucidate the normal functions of this protein, as well as the mechanisms
      underlying PD pathologies.

PMID- 29321726
TI  - The Role of L-type Calcium Channels in Olfactory Learning and Its Modulation by
      Norepinephrine.
AB  - L type calcium channels (LTCCs) are prevalent in different systems and hold
      immense importance for maintaining/performing selective functions. In the nervous
      system, CaV1.2 and CaV1.3 are emerging as critical modulators of neuronal
      functions. Although the general role of these calcium channels in modulating
      synaptic plasticity and memory has been explored, their role in olfactory
      learning is not well understood. In this review article we first discuss the role
      of LTCCs in olfactory learning especially focusing on early odor preference
      learning in neonate rodents, presenting evidence that while NMDARs initiate
      stimulus-specific learning, LTCCs promote protein-synthesis dependent long-term
      memory (LTM). Norepinephrine (NE) release from the locus coeruleus (LC) is
      essential for early olfactory learning, thus noradrenergic modulation of LTCC
      function and its implication in olfactory learning is discussed here. We then
      address the differential roles of LTCCs in adult learning and learning in aged
      animals.

PMID- 29321727
TI  - Spatial Representation of Hippocampal Place Cells in a T-Maze with an Aversive
      Stimulation.
AB  - The hippocampus contains place cells representing spaces in an environment, and
      these place cells have been suggested to play a fundamental role in the formation
      of a cognitive map for spatial processing. However, how alterations in the firing
      patterns of place cells in response to aversive events encode the locations tied
      to these aversive events is unknown. Here, we analyzed spiking patterns of place
      cell ensembles in the dorsal hippocampal CA1 region of rats performing a T-maze
      alternation task with an aversive air-puff stimulation applied at a specific
      location on one side of a trajectory. The intensity of the air puff was adjusted
      so that the rats decreased their running speed before passing the aversive
      location. The addition of the aversive stimulus induced reorganization of place
      cell ensembles on both left and right trajectories with and without the aversive
      stimulus, respectively. Specifically, the animals showed a more abundant spatial
      representation in the vicinity of the aversive location. Removing the aversive
      stimulus induced new spatial firing patterns on both of the trajectories that
      differed from those both before and during application of the aversive stimulus.
      These results demonstrate that hippocampal spatial maps are flexibly reorganized
      to represent particular aversive events.

PMID- 29321729
TI  - The Superior Fronto-Occipital Fasciculus in the Human Brain Revealed by Diffusion
      Spectrum Imaging Tractography: An Anatomical Reality or a Methodological
      Artifact?
AB  - The existence of the superior fronto-occipital fasciculus (SFOF) in the human
      brain remains controversial. The aim of the present study was to clarify the
      existence, course, and terminations of the SFOF. High angular diffusion spectrum
      imaging (DSI) analysis was performed on six healthy adults and on a template of
      842 subjects from the Human Connectome Project. To verify tractography results,
      we performed fiber microdissections of four post-mortem human brains. Based on
      DSI tractography, we reconstructed the SFOF in the subjects and the template from
      the Human Connectome Project that originated from the rostral and medial parts of
      the superior and middle frontal gyri. By tractography, we found that the fibers
      formed a compact fascicle at the level of the anterior horn of the lateral
      ventricle coursing above the head of caudate nucleus, medial to the corona
      radiate and under the corpus callosum (CC), and terminated at the parietal region
      via the lower part of the caudate nucleus. We consider that this fiber bundle
      observed by tractography is the SFOF, although it terminates mainly at the
      parietal region, rather than occipital lobe. By contrast, we were unable to
      identify a fiber bundle corresponding to the SFOF in our fiber dissection study.
      Although we did not provide definite evidence of the SFOF in the human brain,
      these findings may be useful for future studies in this field.

PMID- 29321730
TI  - Rhythmic Calcium Events in the Lamina Propria Network of the Urinary Bladder of
      Rat Pups.
AB  - The lamina propria contains a dense network of cells, including interstitial
      cells (ICs), that may play a role in bladder function by modulating communication
      between urothelium, nerve fibers and smooth muscle or acting as pacemakers.
      Transient receptor potential vanilloid 4 (TRPV4) channels allow cation influx and
      may be involved in sensing stretch or chemical irritation in urinary bladder.
      Urothelium was removed from rats (P0-Adult), cut into strips, and loaded with a
      Ca2+ fluorescent dye (Fluo-2 AM leak resistant or Cal 520) for 90 min (35-37
      degrees C) to measure Ca2+ events. Ca2+ events were recorded for a period of 60
      seconds (s) in control and after drug treatment. A heterogeneous network of cells
      was identified at the interface of the urothelium and lamina propria of postnatal
      rat pups, aged <= postnatal (P) day 21, with diverse morphology (round, fusiform,
      stellate with numerous projections) and expressing platelet-derived growth factor
      receptor alpha (PDGFRalpha)- and TRPV4-immunoreactivity (IR). Ca2+ transients
      occurred at a slow frequency with an average interval of 30 +/- 8.6 s. Waveform
      analyses of Ca2+ transients in cells in the lamina propria network revealed long
      duration Ca2+ events with slow upstrokes. We observed slow propagating waves of
      activity in the lamina propria network that displayed varying degrees of
      coupling. Application of the TRPV4 agonist, GSK1016790 (100 nM), increased the
      duration of Ca2+ events, the number of cells with Ca2+ events and the integrated
      Ca2+ activity corresponding to propagation of activity among cells in the lamina
      propria network. However, GSK2193874 (1 MUM), a potent antagonist of TRPV4
      channels, was without effect. ATP (1 MUM) perfusion increased the number of cells
      in the lamina propria exhibiting Ca2+ events and produced tightly coupled network
      activity. These findings indicate that ATP and TRPV4 can activate cells in the
      laminar propria network, leading to the appearance of organized propagating
      wavefronts.

PMID- 29321732
TI  - Discrete Serotonin Systems Mediate Memory Enhancement and Escape Latencies after
      Unpredicted Aversive Experience in Drosophila Place Memory.
AB  - Feedback mechanisms in operant learning are critical for animals to increase
      reward or reduce punishment. However, not all conditions have a behavior that can
      readily resolve an event. Animals must then try out different behaviors to better
      their situation through outcome learning. This form of learning allows for novel
      solutions and with positive experience can lead to unexpected behavioral
      routines. Learned helplessness, as a type of outcome learning, manifests in part
      as increases in escape latency in the face of repeated unpredicted shocks. Little
      is known about the mechanisms of outcome learning. When fruit fly
      Drosophilamelanogaster are exposed to unpredicted high temperatures in a place
      learning paradigm, flies both increase escape latencies and have a higher memory
      when given control of a place/temperature contingency. Here we describe discrete
      serotonin neuronal circuits that mediate aversive reinforcement, escape
      latencies, and memory levels after place learning in the presence and absence of
      unexpected aversive events. The results show that two features of learned
      helplessness depend on the same modulatory system as aversive reinforcement.
      Moreover, changes in aversive reinforcement and escape latency depend on local
      neural circuit modulation, while memory enhancement requires larger modulation of
      multiple behavioral control circuits.

PMID- 29321728
TI  - Modulation of Hippocampal Circuits by Muscarinic and Nicotinic Receptors.
AB  - This article provides a review of the effects of activation of muscarinic and
      nicotinic receptors on the physiological properties of circuits in the
      hippocampal formation. Previous articles have described detailed computational
      hypotheses about the role of cholinergic neuromodulation in enhancing the
      dynamics for encoding in cortical structures and the role of reduced cholinergic
      modulation in allowing consolidation of previously encoded information. This
      article will focus on addressing the broad scope of different modulatory effects
      observed within hippocampal circuits, highlighting the heterogeneity of
      cholinergic modulation in terms of the physiological effects of activation of
      muscarinic and nicotinic receptors and the heterogeneity of effects on different
      subclasses of neurons.

PMID- 29321733
TI  - Stress Induces Contextual Blindness in Lotteries and Coordination Games.
AB  - In this paper, we study how stress affects risk taking in three tasks: individual
      lotteries, Stag Hunt (coordination) games, and Hawk-Dove (anti-coordination)
      games. Both control and stressed subjects take more risks in all three tasks when
      the value of the safe option is decreased and in lotteries when the expected gain
      is increased. Also, subjects take longer to take decisions when stakes are high,
      when the safe option is less attractive and in the conceptually more difficult
      Hawk-Dove game. Stress (weakly) increases reaction times in those cases. Finally,
      our main result is that the behavior of stressed subjects in lotteries, Stag Hunt
      and Hawk-Dove are all highly predictive of each other (p-value < 0.001 for all
      three pairwise correlations). Such strong relationship is not present in our
      control group. Our results illustrate a "contextual blindness" caused by stress.
      The mathematical and behavioral tensions of Stag Hunt and Hawk-Dove games are
      axiomatically different, and we should expect different behavior across these
      games, and also with respect to the individual task. A possible explanation for
      the highly significant connection across tasks in the stress condition is that
      stressed subjects habitually rely on one mechanism to make a decision in all
      contexts whereas unstressed subjects utilize a more cognitively flexible
      approach.

PMID- 29321731
TI  - Behavioral Modulation by Spontaneous Activity of Dopamine Neurons.
AB  - Dopamine modulates a variety of animal behaviors that range from sleep and
      learning to courtship and aggression. Besides its well-known phasic firing to
      natural reward, a substantial number of dopamine neurons (DANs) are known to
      exhibit ongoing intrinsic activity in the absence of an external stimulus. While
      accumulating evidence points at functional implications for these intrinsic
      "spontaneous activities" of DANs in cognitive processes, a causal link to
      behavior and its underlying mechanisms has yet to be elucidated. Recent
      physiological studies in the model organism Drosophila melanogaster have
      uncovered that DANs in the fly brain are also spontaneously active, and that this
      activity reflects the behavioral/internal states of the animal. Strikingly,
      genetic manipulation of basal DAN activity resulted in behavioral alterations in
      the fly, providing critical evidence that links spontaneous DAN activity to
      behavioral states. Furthermore, circuit-level analyses have started to reveal
      cellular and molecular mechanisms that mediate or regulate spontaneous DAN
      activity. Through reviewing recent findings in different animals with the major
      focus on flies, we will discuss potential roles of this physiological phenomenon
      in directing animal behaviors.

PMID- 29321735
TI  - ArControl: An Arduino-Based Comprehensive Behavioral Platform with Real-Time
      Performance.
AB  - Studying animal behavior in the lab requires reliable delivering stimulations and
      monitoring responses. We constructed a comprehensive behavioral platform
      (ArControl: Arduino Control Platform) that was an affordable, easy-to-use, high
      performance solution combined software and hardware components. The hardware
      component was consisted of an Arduino UNO board and a simple drive circuit. As
      for software, the ArControl provided a stand-alone and intuitive GUI (graphical
      user interface) application that did not require users to master scripts. The
      experiment data were automatically recorded with the built in DAQ (data
      acquisition) function. The ArControl also allowed the behavioral schedule to be
      entirely stored in and operated on the Arduino chip. This made the ArControl a
      genuine, real-time system with high temporal resolution (<1 ms). We tested the
      ArControl, based on strict performance measurements and two mice behavioral
      experiments. The results showed that the ArControl was an adaptive and reliable
      system suitable for behavioral research.

PMID- 29321736
TI  - Commentary: Musicians' Online Performance during Auditory and Visual Statistical
      Learning Tasks.

PMID- 29321737
TI  - Propofol and Sevoflurane Differentially Modulate Cortical Depolarization
      following Electric Stimulation of the Ventrobasal Thalamus.
AB  - The neuronal mechanisms how anesthetics lead to loss of consciousness are
      unclear. Thalamocortical interactions are crucially involved in conscious
      perception; hence the thalamocortical network might be a promising target for
      anesthetic modulation of neuronal information pertaining to arousal and waking
      behavior. General anesthetics affect the neurophysiology of the thalamus and the
      cortex but the exact mechanisms of how anesthetics interfere with processing
      thalamocortical information remain to be elucidated. Here we investigated the
      effect of the anesthetic agents sevoflurane and propofol on thalamocortical
      network activity in vitro. We used voltage-sensitive dye imaging techniques to
      analyze the cortical depolarization in response to stimulation of the thalamic
      ventrobasal nucleus in brain slices from mice. Exposure to sevoflurane globally
      decreased cortical depolarization in a dose-dependent manner. Sevoflurane reduced
      the intensity and extent of cortical depolarization and delayed thalamocortical
      signal propagation. In contrast, propofol neither affected area nor amplitude of
      cortical depolarization. However, propofol exposure resulted in regional changes
      in spatial distribution of maximum fluorescence intensity in deep regions of the
      cortex. In summary, our experiments revealed substance-specific effects on the
      thalamocortical network. Functional changes of the neuronal network are known to
      be pivotally involved in the anesthetic-induced loss of consciousness. Our
      findings provide further evidence that the mechanisms of anesthetic-mediated loss
      of consciousness are drug- and pathway-specific.

PMID- 29321739
TI  - Brain Aging: Uncovering Cortical Characteristics of Healthy Aging in Young
      Adults.
AB  - Despite extensive research in the field of aging neuroscience, it still remains
      unclear whether age related cortical changes can be detected in different
      functional networks of younger adults and whether these networks respond
      identically to healthy aging. We collected high-resolution brain anatomical data
      from 56 young healthy adults (mean age = 30.8 +/- 8.1 years, 29 males). We
      performed whole brain parcellation into seven functional networks, including
      visual, somatomotor, dorsal attention, ventral attention, limbic, frontoparietal
      and default mode networks. We estimated intracranial volume (ICV) and averaged
      cortical thickness (CT), cortical surface area (CSA) and cortical volume (CV)
      over each hemisphere as well as for each network. Averaged cortical measures over
      each hemisphere, especially CT and CV, were significantly lower in older
      individuals compared to younger ones (one-way ANOVA, p < 0.05, corrected for
      multiple comparisons). There were negative correlations between age and averaged
      CT and CV over each hemisphere (p < 0.05, corrected for multiple comparisons) as
      well as between age and ICV (p = 0.05). Network level analysis showed that age
      was negatively correlated with CT for all functional networks (p < 0.05,
      corrected for multiple comparisons), apart from the limbic network. While age was
      unrelated to CSA, it was negatively correlated with CV across several functional
      networks (p < 0.05, corrected for multiple comparisons). We also showed positive
      associations between CV and CT and between CV and CSA for all networks (p < 0.05,
      corrected for multiple comparisons). We interpret the lack of association between
      age and CT of the limbic network as evidence that the limbic system may be
      particularly resistant to age-related declines during this period of life,
      whereas the significant age-related declines in averaged CT over each hemisphere
      as well as in all other six networks suggests that CT may serve as a reliable
      biomarker to capture the effect of normal aging. Due to the simultaneous
      dependence of CV on CT and CSA, CV was unable to identify such effects of normal
      aging consistently for the other six networks, but there were negative
      associations observed between age and averaged CV over each hemisphere as well as
      between age and ICV. Our findings suggest that the identification of early
      cortical changes within various functional networks during normal aging might be
      useful for predicting the effect of aging on the efficiency of functional
      performance even during early adulthood.

PMID- 29321734
TI  - Immediate-Early Genes Modulation by Antipsychotics: Translational Implications
      for a Putative Gateway to Drug-Induced Long-Term Brain Changes.
AB  - An increasing amount of research aims at recognizing the molecular mechanisms
      involved in long-lasting brain architectural changes induced by antipsychotic
      treatments. Although both structural and functional modifications have been
      identified following acute antipsychotic administration in humans, currently
      there is scarce knowledge on the enduring consequences of these acute changes.
      New insights in immediate-early genes (IEGs) modulation following acute or
      chronic antipsychotic administration may help to fill the gap between primary
      molecular response and putative long-term changes. Moreover, a critical appraisal
      of the spatial and temporal patterns of IEGs expression may shed light on the
      functional "signature" of antipsychotics, such as the propensity to induce motor
      side effects, the potential neurobiological mechanisms underlying the differences
      between antipsychotics beyond D2 dopamine receptor affinity, as well as the
      relevant effects of brain region-specificity in their mechanisms of action. The
      interest for brain IEGs modulation after antipsychotic treatments has been
      revitalized by breakthrough findings such as the role of early genes in
      schizophrenia pathophysiology, the involvement of IEGs in epigenetic mechanisms
      relevant for cognition, and in neuronal mapping by means of IEGs expression
      profiling. Here we critically review the evidence on the differential modulation
      of IEGs by antipsychotics, highlighting the association between IEGs expression
      and neuroplasticity changes in brain regions impacted by antipsychotics, trying
      to elucidate the molecular mechanisms underpinning the effects of this class of
      drugs on psychotic, cognitive and behavioral symptoms.

PMID- 29321738
TI  - Cognitive-Motor Interference during Walking in Older Adults with Probable Mild
      Cognitive Impairment.
AB  - Although several studies have shown that dual-tasking (DT) mobility is impaired
      in Alzheimer's disease, studies on the effects of DT conditions in probable Mild
      Cognitive Impairment (pMCI) have not yielded unequivocal results. The objectives
      of the study were to (1) examine the effect of a concurrent task on a complex
      walking task in adults with cognitive impairment; and (2) determine whether the
      effect varied with different difficulty levels of the concurrent task.
      Furthermore, the study was designed to evaluate the Trail-Walking Test (TWT) as a
      potential detection tool for MCI. We examined DT performance in 42 young adults
      (mean age 23.9 +/- 1.98), and 43 older adults (mean age 68.2 +/- 6.42). The MoCA
      was used to stratify the subjects into those with and without pMCI. DT was
      assessed using the TWT: participants completed 5 trials each of walking along a
      fixed pathway, stepping on targets with increasing sequential numbers (i.e., 1-2
      ...-15), and increasing sequential numbers and letters (i.e., 1-A-2-B-3-...-8).
      Motor and cognitive DT effects (DTE) were calculated for each task. ROC curves
      were used to distinguish younger and healthy older adults from older adults with
      pMCI. The TWT showed excellent test-retest reliability across all conditions and
      groups (ICC : 0.83-0.97). SEM% was also low (<11%) as was the MDC95% (<30%).
      Within the DT conditions, the pMCI group showed significantly longer durations
      for all tasks regardless of the cognitive load compared to the younger and the
      healthy older adults. The motor DTEs were greatest for the complex condition in
      older adults with pMCI more so than in comparison with younger and healthy older
      adults. ROC analyses confirmed that only the tasks with higher cognitive load
      could differentiate older adults with pMCI from controls (area under the curve
      >0.7, p < 0.05). The TWT is a reliable DT mobility measure in people with pMCI.
      However, the condition with high cognitive load is more sensitive than the
      condition with low cognitive load in identifying pMCI. The TWT-3 thus could serve
      as a screening tool for early detection of individuals with pMCI. Future studies
      need to determine the neural correlates for cognitive-motor interference in older
      adults with pMCI.

PMID- 29321740
TI  - A Non-imaging High Throughput Approach to Chemical Library Screening at the
      Unmodified Adenosine-A3 Receptor in Living Cells.
AB  - Recent advances in fluorescent ligand technology have enabled the study of G
      protein-coupled receptors in their native environment without the need for
      genetic modification such as addition of N-terminal fluorescent or bioluminescent
      tags. Here, we have used a non-imaging plate reader (PHERAstar FS) to monitor the
      binding of fluorescent ligands to the human adenosine-A3 receptor (A3AR; CA200645
      and AV039), stably expressed in CHO-K1 cells. To verify that this method was
      suitable for the study of other GPCRs, assays at the human adenosine-A1 receptor,
      and beta1 and beta2 adrenoceptors (beta1AR and beta2AR; BODIPY-TMR-CGP-12177)
      were also carried out. Affinity values determined for the binding of the
      fluorescent ligands CA200645 and AV039 to A3AR for a range of classical adenosine
      receptor antagonists were consistent with A3AR pharmacology and correlated well
      (R2 = 0.94) with equivalent data obtained using a confocal imaging plate reader
      (ImageXpress Ultra). The binding of BODIPY-TMR-CGP-12177 to the beta1AR was
      potently inhibited by low concentrations of the beta1-selective antagonist CGP
      20712A (pKi 9.68) but not by the beta2-selective antagonist ICI 118551(pKi 7.40).
      Furthermore, in experiments conducted in CHO K1 cells expressing the beta2AR this
      affinity order was reversed with ICI 118551 showing the highest affinity (pKi
      8.73) and CGP20712A (pKi 5.68) the lowest affinity. To determine whether the
      faster data acquisition of the non-imaging plate reader (~3 min per 96-well
      plate) was suitable for high throughput screening (HTS), we screened the LOPAC
      library for inhibitors of the binding of CA200645 to the A3AR. From the initial
      1,263 compounds evaluated, 67 hits (defined as those that inhibited the total
      binding of 25 nM CA200645 by >=40%) were identified. All compounds within the
      library that had medium to high affinity for the A3AR (pKi >=6) were successfully
      identified. We found three novel compounds in the library that displayed
      unexpected sub-micromolar affinity for the A3AR. These were K114 (pKi 6.43),
      retinoic acid p-hydroxyanilide (pKi 6.13) and SU 6556 (pKi 6.17). Molecular
      docking of these latter three LOPAC library members provided a plausible set of
      binding poses within the vicinity of the established orthosteric A3AR binding
      pocket. A plate reader based library screening using an untagged receptor is
      therefore possible using fluorescent ligand opening the possibility of its use in
      compound screening at natively expressed receptors.

PMID- 29321741
TI  - ATP Modifies the Proteome of Extracellular Vesicles Released by Microglia and
      Influences Their Action on Astrocytes.
AB  - Extracellular ATP is among molecules promoting microglia activation and inducing
      the release of extracellular vesicles (EVs), which are potent mediators of
      intercellular communication between microglia and the microenvironment. We
      previously showed that EVs produced under ATP stimulation (ATP-EVs) propagate a
      robust inflammatory reaction among astrocytes and microglia in vitro and in mice
      with subclinical neuroinflammation (Verderio et al., 2012). However, the proteome
      of EVs released upon ATP stimulation has not yet been elucidated. In this study
      we applied a label free proteomic approach to characterize the proteome of EVs
      released constitutively and during microglia activation with ATP. We show that
      ATP drives sorting in EVs of a set of proteins implicated in cell
      adhesion/extracellular matrix organization, autophagy-lysosomal pathway and
      cellular metabolism, that may influence the response of recipient astrocytes to
      EVs. These data provide new clues to molecular mechanisms involved in microglia
      response to ATP and in microglia signaling to the environment via EVs.

PMID- 29321743
TI  - The Effects of Electronic Cigarette (ECIG)-Generated Aerosol and Conventional
      Cigarette Smoke on the Mucociliary Transport Velocity (MTV) Using the Bullfrog
      (R. catesbiana) Palate Paradigm.
AB  - Background: While ECIGs are under scrutiny concerning safety, particularly in
      reference to the physiological impact that aerosolized ECIG liquid (E-liquid) may
      have on respiratory tissues, others believe that ECIGs are a "Harm Reduction"
      alternative to conventional cigarettes. Previous studies investigating ciliated
      respiratory epithelium indicate that smoking shortens cilia length, reduces cilia
      beat frequency and disrupts respiratory epithelium, which most likely contributes
      to the inhibition of mucocilliary clearance. Monitoring mucous clearance of
      respiratory tissues exposed to ECIG-generated aerosol or conventional cigarette
      smoke, as indexed by mucous transport velocity (MTV), is one way to gauge the
      impact aerosol and smoke have on the respiratory tract. Therefore, we designed an
      experiment to test the effect of ECIG-generated aerosol and smoke on MTV using
      the frog palate paradigm. Methods: Peristaltic pumps transport ECIG-generated
      aerosol and conventional cigarette smoke into custom-made chambers containing
      excised bullfrog palates. MTVs were determined before exposure, immediately after
      exposure and approximately 1 day following exposure. MTVs were also determined
      (at the same time points) for palates exposed to air (control). Surface and cross
      sectional SEM images of palates from all three groups were obtained to support
      MTV data. Results: The results indicate that ECIG-generated aerosol has a modest
      inhibitory effect (p < 0.05) on MTV 1 day post-exposure (0.09 +/- 0.01) compared
      to control MTV (0.16 +/- 0.03 mm/s). In contrast, smoke completely inhibits MTV
      from 0.14 +/- 0.03 mm/s immediately before exposure to 0.00 mm/sec immediately
      after exposure and the MTV is unable to recover 1 day later. SEM images of
      control palates and palates exposed to ECIG-generated aerosol both show cilia
      throughout their epithelial surface, while some areas of palates exposed to smoke
      are completely devoid of cilia. Additionally, the epithelial thickness of aerosol
      exposed palates appears thicker than control palates while smoke-exposed palates
      appear to be thinner due to epithelial disruption. Conclusions: These results
      indicate that ECIG-generated aerosol has only a modest effect on mucocilary
      clearance of bullfrog palates and aerosol sedimentation accounts for epithelial
      thickening. In accordance with the primary literature, conventional cigarette
      smoke dramatically inhibits mucociliary clearance and is, in part, due to
      decreased number of cilia and disruption of the smoke-exposed epithelium.

PMID- 29321742
TI  - Respiratory Frequency during Exercise: The Neglected Physiological Measure.
AB  - The use of wearable sensor technology for athlete training monitoring is growing
      exponentially, but some important measures and related wearable devices have
      received little attention so far. Respiratory frequency (fR), for example, is
      emerging as a valuable measurement for training monitoring. Despite the
      availability of unobtrusive wearable devices measuring fR with relatively good
      accuracy, fR is not commonly monitored during training. Yet fR is currently
      measured as a vital sign by multiparameter wearable devices in the military
      field, clinical settings, and occupational activities. When these devices have
      been used during exercise, fR was used for limited applications like the
      estimation of the ventilatory threshold. However, more information can be gained
      from fR. Unlike heart rate, [Formula: see text]O2, and blood lactate, fR is
      strongly associated with perceived exertion during a variety of exercise
      paradigms, and under several experimental interventions affecting performance
      like muscle fatigue, glycogen depletion, heat exposure and hypoxia. This suggests
      that fR is a strong marker of physical effort. Furthermore, unlike other
      physiological variables, fR responds rapidly to variations in workload during
      high-intensity interval training (HIIT), with potential important implications
      for many sporting activities. This Perspective article aims to (i) present
      scientific evidence supporting the relevance of fR for training monitoring; (ii)
      critically revise possible methodologies to measure fR and the accuracy of
      currently available respiratory wearables; (iii) provide preliminary indication
      on how to analyze fR data. This viewpoint is expected to advance the field of
      training monitoring and stimulate directions for future development of sports
      wearables.

PMID- 29321745
TI  - Commentary: Tensiomyographic Markers Are Not Sensitive for Monitoring Muscle
      Fatigue in Elite Youth Athletes: A Pilot Study.

PMID- 29321744
TI  - Nitrite-Mediated Hypoxic Vasodilation Predicted from Mathematical Modeling and
      Quantified from in Vivo Studies in Rat Mesentery.
AB  - Nitric oxide (NO) generated from nitrite through nitrite reductase activity in
      red blood cells has been proposed to play a major role in hypoxic vasodilation.
      However, we have previously predicted from mathematical modeling that much more
      NO can be derived from tissue nitrite reductase activity than from red blood cell
      nitrite reductase activity. Evidence in the literature suggests that tissue
      nitrite reductase activity is associated with xanthine oxidoreductase (XOR)
      and/or aldehyde oxidoreductase (AOR). We investigated the role of XOR and AOR in
      nitrite-mediated vasodilation from computer simulations and from in vivo
      exteriorized rat mesentery experiments. Vasodilation responses to nitrite in the
      superfusion medium bathing the mesentery equilibrated with 5% O2 (normoxia) or
      zero O2 (hypoxia) at either normal or acidic pH were quantified. Experiments were
      also conducted following intraperitoneal (IP) injection of nitrite before and
      after inhibiting XOR with allopurinol or inhibiting AOR with raloxifene. Computer
      simulations for NO and O2 transport using reaction parameters reported in the
      literature were also conducted to predict nitrite-dependent NO production from
      XOR and AOR activity as a function of nitrite concentration, PO2 and pH.
      Experimentally, the largest arteriolar responses were found with nitrite >10 mM
      in the superfusate, but no statistically significant differences were found with
      hypoxic and acidic conditions in the superfusate. Nitrite-mediated vasodilation
      with IP nitrite injections was reduced or abolished after inhibiting XOR with
      allopurinol (p < 0.001). Responses to IP nitrite before and after inhibiting AOR
      with raloxifene were not as consistent. Our mathematical model predicts that
      under certain conditions, XOR and AOR nitrite reductase activity in tissue can
      significantly elevate smooth muscle cell NO and can serve as a compensatory
      pathway when endothelial NO production is limited by hypoxic conditions. Our
      theoretical and experimental results provide further evidence for a role of
      tissue nitrite reductases to contribute additional NO to compensate for reduced
      NO production by endothelial nitric oxide synthase during hypoxia. Our
      mathematical model demonstrates that under extreme hypoxic conditions with acidic
      pH, endogenous nitrite levels alone can be sufficient for a functionally
      significant increase in NO bioavailability. However, these conditions are
      difficult to achieve experimentally.

PMID- 29321747
TI  - Lower Choline-Containing Metabolites/Creatine (Cr) Rise and Failure to Sustain
      NAA/Cr Levels in the Dorsolateral Prefrontal Cortex Are Associated with
      Depressive Episode Recurrence under Maintenance Therapy: A Proton Magnetic
      Resonance Spectroscopy Retrospective Cohort Study.
AB  - Background: The aim of this study was to evaluate the relationship between
      changes in proton magnetic resonance spectroscopy (1H-MRS) parameters at the
      start of the index episode recovery phase and at recurrence in patients with
      recurrent depression who were treated with prolonged maintenance therapy.
      Methods: 1H-MRS parameters were analyzed in 48 patients with recurrent depression
      who required maintenance therapy with antidepressant medication prescribed by a
      psychiatrist and who continued with the same antidepressant during the
      maintenance phase, either to recurrence of depression, completion of the 10-year
      observation period, or the start of the withdrawal phase (tapering-off
      antidepressant). N-acetylaspartate (NAA), choline-containing metabolites (Cho),
      creatine (Cr), and glutamine/glutamate were measured at the start of the recovery
      phase and 6 months later. Results: Recurrent depressive episodes occurred in 20
      patients. These individuals had a smaller increase in Cho/Cr after the beginning
      of the recovery phase compared to the non-recurrent patient group and also
      exhibited a decreased NAA/Cr ratio. Conclusion: Sustainable NAA and increased Cho
      levels at the onset of the recovery phase of the index episode are early markers
      of antidepressant effectiveness associated with a lower risk of major depressive
      disorder recurrence. The NAA and Cho changes in the non-recurrent group may be
      attributable to increased brain resilience, contrary to the transient temporal
      effect observed in subjects who experienced a depressive episode.

PMID- 29321746
TI  - Identification of Novel Signal Transduction, Immune Function, and Oxidative
      Stress Genes and Pathways by Topiramate for Treatment of Methamphetamine
      Dependence Based on Secondary Outcomes.
AB  - Background: Topiramate (TPM) is suggested to be a promising medication for
      treatment of methamphetamine (METH) dependence, but the molecular basis remains
      to be elucidated. Methods: Among 140 METH-dependent participants randomly
      assigned to receive either TPM (N = 69) or placebo (N = 71) in a previously
      conducted randomized controlled trial, 50 TPM- and 49 placebo-treated
      participants had a total 212 RNA samples available at baseline, week 8, and week
      12 time points. Following our primary analysis of gene expression data, we
      reanalyzed the microarray expression data based on a latent class analysis of
      binary secondary outcomes during weeks 1-12 that provided a classification of 21
      responders and 31 non-responders with consistent responses at both time points.
      Results: Based on secondary outcomes, 1,381, 576, 905, and 711 differentially
      expressed genes at nominal P values < 0.05 were identified in responders versus
      non-responders for week 8 TPM, week 8 placebo, week 12 TPM, and week 12 placebo
      groups, respectively. Among 1,381 genes identified in week 8 TPM responders, 359
      genes were identified in both week 8 and week 12 TPM groups, of which 300 genes
      were exclusively detected in TPM responders. Of them, 32 genes had nominal P
      values < 5 * 10-3 at either week 8 or week 12 and false discovery rates < 0.15 at
      both time points with consistent directions of gene expression changes, which
      include GABARAPL1, GPR155, and IL15RA in GABA receptor signaling that represent
      direct targets for TPM. Analyses of these 300 genes revealed 7 enriched pathways
      belonging to neuronal function/synaptic plasticity, signal transduction,
      inflammation/immune function, and oxidative stress response categories. No
      pathways were enriched for 72 genes exclusively detected in both week 8 and week
      12 placebo groups. Conclusion: This secondary analysis study of gene expression
      data from a TPM clinical trial not only yielded consistent results with those of
      primary analysis but also identified additional new genes and pathways on TPM
      response to METH addiction.

PMID- 29321748
TI  - Silencing of Viral Elements: An Available Cure for Schizophrenia?

PMID- 29321749
TI  - Gender and Age Effects on the Trajectory of Depression in Opioid Users during
      Methadone Maintenance Treatment.
AB  - Introduction: Both heroin use and depression are significant health problems.
      Methadone maintenance treatment (MMT) can be of great benefit to heroin users.
      However, changes in the level of depression in heroin users during MMT are not
      clear. Gender and age are also important factors in the development of
      depression, and whether gender and age moderate changes in depression in heroin
      users during MMT warrants further study. This study aimed to explore: (1) the
      trajectory of depression in opioid users during MMT and (2) the moderating
      effects of gender and age on the trajectory of depression in opioid users
      receiving MMT. Method: A total of 294 intravenous heroin users were recruited
      into this 9-month observational study. The level of depression was measured at
      the intake interview and at follow-up interviews every 3 months. A latent growth
      model was used to analyze the trajectory of the level of depression among the
      participants. Results: Depression improved rapidly during the first 3 months of
      MMT and slowly after the first 3 months in both the female and male heroin users.
      There was no gender difference in the level of depression at each follow-up
      point. The level of depression in the female heroin users decreased faster than
      that in the male heroin users. In addition, the level of depression in the
      younger heroin users decreased faster than that in the older subjects.
      Conclusion: Depression in female and younger heroin users improved more rapidly
      than in male and older subjects, respectively.

PMID- 29321750
TI  - Psychometric Properties of the Cognitive Emotion Regulation Questionnaire (CERQ)
      in Patients with Fibromyalgia Syndrome.
AB  - Given that Fibromyalgia Syndrome (FMS) is associated with problems in emotion
      regulation, the importance of assessing this construct is widely acknowledged by
      clinical psychologists and pain specialists. Although the Cognitive Emotion
      Regulation Questionnaire (CERQ) is a self-report measure used worldwide, there
      are no data on its psychometric properties in patients with FMS. This study
      analyzed the dimensionality, reliability, and validity of the CERQ in a sample of
      231 patients with FMS. Given that "fibrofog" is one of the most disabling FMS
      symptoms, in the present study, items in the CERQ were grouped by dimension. This
      change in item presentation was conceived as an efficient way of facilitating
      responses as a result of a clear understanding of what the items related to each
      dimension are attempting to measure. The following battery of measures was
      administered: the CERQ, the Revised Fibromyalgia Impact Questionnaire, the Pain
      Catastrophizing Scale, the Center for Epidemiologic Studies Depression Scale, and
      the State-Trait Anxiety Inventory. Four models of the CERQ structure were
      examined and confirmatory factor analyses supported the original factor model,
      consisting of nine factors-Self-blame, Acceptance, Rumination, Positive
      refocusing, Refocus on planning, Positive reappraisal, Putting into perspective,
      Catastrophizing, and Other-blame. There was minimal overlap between CERQ
      subscales and their internal consistency was adequate. Correlational and
      regression analyses supported the construct validity of the CERQ. Our findings
      indicate that the CERQ (items-grouped version) is a sound instrument for
      assessing cognitive emotion regulation in patients with FMS.

PMID- 29321751
TI  - Sensation Seeking, Non-contextual Decision Making, and Driving Abilities As
      Measured through a Moped Simulator.
AB  - The general aim of the present study was to explore the relations between driving
      style (assessed through a moped riding simulator) and psychological variables
      such as sensation seeking and decision making. Because the influences of
      sensation seeking and decision making on driving styles have been studied
      separately in the literature, we have tried to investigate their mutual relations
      so as to include them in a more integrated framework. Participants rode the Honda
      Riding Trainer (HRT) simulator, filled in the Sensation Seeking Scale V (SSS V),
      and performed the Iowa Gambling Task (IGT). A cluster analysis of the HRT riding
      indexes identified three groups: Prudent, Imprudent, and Insecure riders. First,
      the results showed that Insecure males seek thrills and adventure less than both
      Prudent males and Insecure females, whereas Prudent females are less disinhibited
      than both Prudent males and Insecure females. Moreover, concerning the relations
      among SSS, decision making as measured by the IGT, and riding performance, high
      thrill and adventure seekers performed worse in the simulator only if they were
      also bad decision makers, indicating that these two traits jointly contribute to
      the quality of riding performance. From an applied perspective, these results
      also provide useful information for the development of protocols for assessing
      driving abilities among novice road users. Indeed, the relation between risk
      proneness and riding style may allow for the identification of road-user
      populations who require specific training.

PMID- 29321752
TI  - Differential Classical Conditioning of the Nocebo Effect: Increasing Heat-Pain
      Perception without Verbal Suggestions.
AB  - Background: Nocebo effects, including nocebo hyperalgesia, are a common
      phenomenon in clinical routine with manifold negative consequences. Both explicit
      expectations and learning by conditioning are known to induce nocebo effects, but
      the specific role of conditioning remains unclear, because conditioning is rarely
      implemented independent of verbal suggestions. Further, although pain is a
      multidimensional phenomenon, nocebo effects are usually assessed in subjective
      ratings only, neglecting, e.g., behavioral aspects. The aim of this study was to
      test whether nocebo hyperalgesia can be learned by conditioning without explicit
      expectations, to assess nocebo effects in different response channels, and to
      exploratively assess, whether contingency awareness is a necessary condition for
      conditioned nocebo hyperalgesia. Methods: Twenty-one healthy volunteers were
      classically conditioned using painful and non-painful heat stimuli that followed
      two different cues. The conditioned nocebo effect was assessed by subjective
      ratings of perceived stimulation intensity on a visual analog scale and a
      behavioral discrimination task, assessing sensitization and habituation in
      response to the same stimulation following the two cues. Results: Results show a
      conditioned nocebo effect indicated by the subjective intensity ratings.
      Conditioned effects were also seen in the behavioral responses, but
      paradoxically, behavioral responses indicated decreased perception after
      conditioning, but only for subjects successfully conditioned as indicated by the
      subjective ratings. Explorative analyses suggested that awareness of the
      contingencies and the different cues was not necessary for successful
      conditioning. Conclusion: Nocebo effects can be learned without inducing
      additional explicit expectations. The dissociation between the two response
      channels, possibly representing the conditioned and a compensatory response,
      highlights the importance of considering different outcomes in nocebo responses
      to fully understand underlying mechanisms. The present results challenge the role
      of explicit expectations in conditioned nocebo effects and are relevant with
      implications in clinical contexts, e.g., when transient adverse effects become
      conditioned.

PMID- 29321754
TI  - The Interplay of Students' School Engagement, School Self-Concept and
      Motivational Relations during Adolescence.
AB  - Existing literature evidences the association between adolescents' school self
      concept and engagement, both concepts being related to students' perception of
      teachers and peers as motivators. However, few longitudinal studies explore the
      interplay of these factors. The present study aims to close this gap, applying
      latent cross-lagged panel design to two-wave data from German adolescent students
      [1088 8th grade students at T1 (Mage = 13.7, SD = 0.53; 53.9% girls) and 845 9th
      grade students at T2 (Mage = 14.86; SD = 0.57; 55% girls) from the initial
      sample]. Besides direct effects, three cross-lagged over-time paths were found to
      be significant: students' perception of peers as positive motivators (PPMs) at
      the beginning of 8th grade (T1) positively predicts their behavioral school
      engagement at the end of 9th grade (T2), as well as emotional school engagement
      at the beginning of 8th grade positively predicts students' perception of PPMs
      1.5 years later. Furthermore, behavioral school engagement at T1 functions as a
      predictor of a student's school self-concept at T2.

PMID- 29321753
TI  - Pragmatic Ability Deficit in Schizophrenia and Associated Theory of Mind and
      Executive Function.
AB  - Deficits in pragmatic abilities have frequently been observed in patients with
      schizophrenia. The objective of the study was to investigate the relationship
      between pragmatic deficits, ToM deficits and executive dysfunctions in
      schizophrenia. A group of 42 schizophrenic patients and 42 healthy controls were
      assessed on irony task (one type of pragmatic language), two subcomponents of ToM
      (cognitive and affective), and three subcomponents of EF (inhibition, updating,
      and switching). The clinical symptoms in schizophrenia were assessed using the
      positive and negative symptoms of schizophrenia. The schizophrenia group
      exhibited significant impairments in all above tasks compared to the control
      group. Correlation results found that irony scores were correlated with the two
      subcomponents of ToM and two of the three subcomponents of EF (inhibition and
      updating). The regression analysis revealed that the cognitive ToM and inhibition
      predicted 9.2% and 29.9% of the variance of irony comprehension in the patient
      group, and inhibition was the best predictor for performance on irony task. Irony
      understanding was related to positive symptoms, but not to negative symptoms. The
      results suggest that the ability to interpret pragmatic language depends on
      schizophrenic patients' ability to infer mental states and the ability of
      inhibition. It provides empirical evidence for a particular target of inhibition
      for rehabilitation and intervention programs developed for schizophrenic
      patients.

PMID- 29321755
TI  - Do Children with Better Inhibitory Control Donate More? Differentiating between
      Early and Middle Childhood and Cool and Hot Inhibitory Control.
AB  - Inhibitory control may play an important part in prosocial behavior, such as
      donating behavior. However, it is not clear at what developmental stage
      inhibitory control becomes associated with donating behavior and which aspects of
      inhibitory control are related to donating behavior during development in early
      to middle childhood. The present study aimed to clarify these issues with two
      experiments. In Experiment 1, 103 3- to 5-year-old preschoolers completed cool
      (Stroop-like) and hot (delay of gratification) inhibitory control tasks and a
      donating task. The results indicated that there were no relationships between
      cool or hot inhibitory control and donating behavior in the whole group and each
      age group of the preschoolers. In Experiment 2, 140 elementary school children in
      Grades 2, 4, and 6 completed cool (Stroop-like) and hot (delay of gratification)
      inhibitory control tasks and a donating task. The results showed that inhibitory
      control was positively associated with donating behavior in the whole group. Cool
      and hot inhibitory control respectively predicted donating behavior in the second
      and sixth graders. Therefore, the present study reveals that donating behavior
      increasingly relies on specific inhibitory control, i.e., hot inhibitory control
      as children grow in middle childhood.

PMID- 29321756
TI  - A Neurodynamic Perspective on Musical Enjoyment: The Role of Emotional
      Granularity.

PMID- 29321757
TI  - Clinical and Phenomenological Characteristics of Patients with Task-Specific
      Lingual Dystonia: Possible Association with Occupation.
AB  - Background: Lingual dystonia is a subtype of oromandibular dystonia, which is a
      movement disorder characterized by involuntary sustained or intermittent
      contraction of the masticatory and/or tongue muscles. Lingual dystonia interferes
      with important daily activities, such as speaking, chewing, and swallowing,
      resulting in vocational and social disability. Objective: The aim of this study
      was to investigate a possible relationship between occupation and the development
      of lingual dystonia. Methods: Phenomenological and clinical characteristics of 95
      patients [53 females (55.8%) and 42 males (44.2%), mean age 48.0 years] with task
      specific, speech-induced lingual dystonia were analyzed. Structured interviews
      were carried out to obtain information regarding primary occupation, including
      overtime work and stress during work. The factors that might have influenced the
      development of lingual dystonia were estimated using multivariate logistic
      regression analysis of the 95 patients with lingual dystonia and 95 controls [68
      females (71.6%) and 27 males (28.4%), mean age 47.2 years] with temporomandibular
      disorders. Results: Overall, 84.2% of the patients had regular occupations; 73.8%
      of the patients with regular occupations reported working overtime more than
      twice a week, and 63.8% of them experienced stress at the workplace. Furthermore,
      82.1% of the patients had engaged in occupations that required them to talk to
      customers or other people under stressful situations over prolonged periods of
      time for many years (mean: 15.6 years). The most common occupation was sales
      representative (17.9%), followed by telephone operator (13.7%), customer service
      representative (10.5%), health care worker (9.5%), waiter or waitress (5.3%),
      receptionist (5.3%), and cashier (5.3%). Twenty-nine patients (30.5%) had tardive
      lingual dystonia. Logistic regression analyses revealed that frequent
      requirements for professional speaking (p = 0.011, odds ratio: 5.66), high stress
      during work (p = 0.043, odds ratio: 5.4), and neuroleptic use (p = 0.032, odds
      ratio: 2.52) were significant contributors to the manifestation of lingual
      dystonia. Conclusion: Professions in which conversations in stressful situations
      are unavoidable may trigger lingual dystonia. Therefore, speech-induced lingual
      dystonia can be regarded as occupational dystonia in certain cases.

PMID- 29321758
TI  - Factors Affecting Volume Changes of the Somatosensory Cortex in Patients with
      Spinal Cord Injury: To Be Considered for Future Neuroprosthetic Design.
AB  - Spinal cord injury (SCI) leads to severe chronic disability, but also to
      secondary adaptive changes upstream to the injury in the brain which are most
      likely induced due to the lack of afferent information. These neuroplastic
      changes are a potential target for innovative therapies such as neuroprostheses,
      e.g., by stimulation in order to evoke sensation or in order to suppress phantom
      limb pain. Diverging results on gray matter atrophy have been reported in
      patients with SCI. Detectability of atrophy seems to depend on the selection of
      the regions of interest, while whole-brain approaches are not sensitive enough.
      In this study, we discussed previous research approaches and analyzed
      differential atrophic changes in incomplete SCI using manual segmentation of the
      somatosensory cortex. Patients with incomplete SCI (ASIA C-D), with cervical (N =
      5) and thoracic (N = 6) injury were included. Time since injury was <=12 months
      in 7 patients, and 144, 152, 216, and 312 months in the other patients. Age at
      the injury was <=26 years in 4 patients and >=50 years in 7 patients. A sample of
      12 healthy controls was included in the study. In contrast to all previous
      studies that used voxel-based morphometry, we performed manual segmentation of
      the somatosensory cortex in the postcentral gyrus from structural magnetic
      resonance images and normalized the calculated volumes against the sum of volumes
      of an automated whole-head segmentation. Volumes were smaller in patients than in
      controls (p = 0.011), and as a tendency, female patients had smaller volumes than
      male patients (p = 0.017, uncorrected). No effects of duration (subacute vs.
      chronic), level of lesion (cervical vs. thoracic), region (left vs. right S1),
      and age at onset (<=26 vs. >=50 years) was found. Our results demonstrate volume
      loss of S1 in incomplete SCI and encourage further research with larger sample
      sizes on volumetric changes in the acute and chronic stage of SCI, in order to
      document the moderating effect of type and location of injury on neuroplastic
      changes. A better understanding of neuroplastic changes in the sensorimotor
      cortex after SCI and its interaction with sex is needed in order to develop
      efficient rehabilitative interventions and neuroprosthetic technologies.

PMID- 29321759
TI  - Deficits in the Proline-Rich Synapse-Associated Shank3 Protein in Multiple
      Neuropsychiatric Disorders.
AB  - Signaling between neurons in the human central nervous system (CNS) is
      accomplished through a highly interconnected network of presynaptic and
      postsynaptic elements essential in the conveyance of electrical and neurochemical
      information. One recently characterized core postsynaptic element essential to
      the efficient operation of this complex network is a relatively abundant ~184.7
      kDa proline-rich synapse-associated cytoskeletal protein known as Shank3 (SH3
      ankyrin repeat domain; encoded at human chr 22q13.33). In this "Perspectives"
      article, we review and comment on current advances in Shank3 research and include
      some original data that show common Shank3 deficits in a number of seemingly
      unrelated human neurological disorders that include sporadic Alzheimer's disease
      (AD), autism spectrum disorder (ASD), bipolar disorder (BD), Phelan-McDermid
      syndrome (PMS; 22q13.3 deletion syndrome), and schizophrenia (SZ). Shank3 was
      also found to be downregulated in the CNS of the transgenic AD (TgAD) 5x familial
      Alzheimer's disease murine model engineered to overexpress the 42 amino acid
      amyloid-beta (Abeta42) peptide. Interestingly, the application of known pro
      inflammatory stressors, such as the Abeta42 peptide and the metal-neurotoxin
      aluminum sulfate, to human neuronal-glial cells in primary culture resulted in a
      significant decrease in the expression of Shank3. These data indicate that
      deficits in Shank3-expression may be one common denominator linking a wide-range
      of human neurological disorders that exhibit a progressive or developmental
      synaptic disorganization that is temporally associated with cognitive decline.

PMID- 29321762
TI  - Aflatoxin-Contaminated Nut Separation by Applied Machinery and Processing Stages
      in Fresh Pistachio Processing Plant.
AB  - In pistachio nuts, aflatoxin is mainly concentrated in the green hull-cracked
      nuts in the orchard even prior to harvest. However, during the hull-removal
      process, the hulls of all nuts including the cracked, identifiable nuts are
      removed causing an important characterization criterion of the contaminated nuts,
      to be lost. This, in turn, makes it harder to detect the contaminated nuts.
      However, during the processing stage, there is a good possibility of sorting the
      contaminated nuts based on their other inherent features, such as specific
      gravity and stain on the hard shell. In this study, we aimed to explore the
      effect of applied processing machinery and related sequences in the aflatoxin
      flow during post-harvest processing and the possible ways of reducing aflatoxin
      contamination in the Iranian pistachio industry. We planned a systematic sampling
      from the main and reject streams in two major prevailing processing methods,
      namely, wet and dry. In the dry processing method, the reject streams such as the
      adhering-hull rejects, air floaters, and manual hand pick-outs from the final
      inspection were found to be significantly more contaminated than the main stream.
      However, in the wet processing method, the input stream was considered highly
      contaminated. Among the sorting stages, only the adhering-hull rejects of the
      sinkers were considered more contaminated than the main stream. A contamination
      removal index was developed and applied to compare the effectiveness of the
      processing procedures. The water flotation tank was deemed responsible for 52.5%
      of aflatoxin contamination removal compared to 2.1% in the air flotation system.
      More effective sorting was achieved by the adhering-hull remover, which was
      preceded by a rubber-drum huller instead of the metal-drum type. Thus, by
      combining the most effective techniques of aflatoxin removal, an improved and
      more efficient method may be designed for pistachio processing plants.

PMID- 29321760
TI  - Optical Coherence Tomography in Patients with Chronic Migraine: Literature Review
      and Update.
AB  - Migraine is a chronic disease characterized by unilateral, pulsating, and often
      moderate-to-severe recurrent episodes of headache with nausea and vomiting. It
      affects approximately 15% of the general population, yet the underlying
      pathophysiological mechanisms are not fully understood. Optical coherence
      tomography (OCT) is a safe and reproducible diagnostic technique that utilizes
      infrared wavelengths and has a sensitivity of 8-10 MUm. It can be used to measure
      thinning of the retinal nerve fiber layer (RNFL) in some neurological disorders.
      Although ophthalmologists are often the first specialists to examine patients
      with migraine, few studies have addressed the involvement of the optic nerve and
      retino-choroidal structures in this group. We reviewed the literature on the
      etiological and pathological mechanisms of migraine and the relationship between
      recurrent constriction of cerebral and retrobulbar vessels and ischemic damage to
      the optic nerve, retina, and choroid. We also assessed the role of OCT for
      measuring peripapillary RNFL thickness and macular and choroidal changes in
      migraine patients. There is considerable evidence of cerebral and retrobulbar
      vascular involvement in the etiology of migraine. Transitory and recurrent
      constriction of the retinal and ciliary arteries may cause ischemic damage to the
      optic nerve, retina, and choroid in patients with migraine. OCT to assess the
      thickness of the peripapillary RNFL, macula, and choroid might increase our
      understanding of the pathophysiology of migraine and facilitate diagnosis of
      retino-choroidal compromise and follow-up of therapy in migraine patients. Future
      studies should determine the usefulness of OCT findings as a biomarker of
      migraine.

PMID- 29321761
TI  - From Bench to Bedside: Translating the Prolactin/Vasoinhibin Axis.
AB  - The prolactin/vasoinhibin axis defines an endocrine system, in which prolactin
      (PRL) and vasoinhibins regulate blood vessel growth and function, the secretion
      of other hormones, inflammatory and immune processes, coagulation, and behavior.
      The core element of the PRL/vasoinhibin axis is the generation of vasoinhibins,
      which consists in the proteolytic cleavage of their precursor molecule PRL.
      Vasoinhibins can interact with multiple different partners to mediate their
      effects in various tissues and anatomical compartments, indicating their
      pleiotropic nature. Based on accumulating knowledge about the PRL/vasoinhibin
      axis, two clinical trials were initiated, in which vasoinhibin levels are the
      target of therapeutic interventions. One trial investigates the effect of
      levosulpiride, a selective dopamine D2-receptor antagonist, on retinal
      alterations in patients with diabetic macular edema and retinopathy. The
      rationale of this trial is that the levosulpiride-induced hyperprolactinemia
      resulting in increased retinal vasoinhibins could lead to beneficiary outcomes in
      terms of a vasoinhibin-mediated antagonization of diabetes-induced retinal
      alterations. Another trial investigated the effect of bromocriptine, a dopamine
      D2-receptor agonist, for the treatment of peripartum cardiomyopathy. The
      rationale of treatment with bromocriptine is the inhibition of vasoinhibin
      generation by substrate depletion to prevent detrimental effects on the
      myocardial microvascularization. The trial demonstrated that bromocriptine
      treatment was associated with a high rate of left ventricular recovery and low
      morbidity and mortality. Therapeutic interventions into the PRL/vasoinhibin axis
      bear the risk of side effects in the areas of blood coagulation, blood pressure,
      and alterations of the mental state.

PMID- 29321763
TI  - Plant Phylogeny and Life History Shape Rhizosphere Bacterial Microbiome of Summer
      Annuals in an Agricultural Field.
AB  - Rhizosphere microbial communities are critically important for soil nitrogen
      cycling and plant productivity. There is evidence that plant species and
      genotypes select distinct rhizosphere communities, however, knowledge of the
      drivers and extent of this variation remains limited. We grew 11 annual species
      and 11 maize (Zea mays subsp. mays) inbred lines in a common garden experiment to
      assess the influence of host phylogeny, growth, and nitrogen metabolism on
      rhizosphere communities. Growth characteristics, bacterial community composition
      and potential activity of extracellular enzymes were assayed at time of
      flowering, when plant nitrogen demand is maximal. Bacterial community composition
      varied significantly between different plant species and genotypes. Rhizosphere
      beta-diversity was positively correlated with phylogenetic distance between plant
      species, but not genetic distance within a plant species. In particular, life
      history traits associated with plant resource acquisition (e.g., longer lifespan,
      high nitrogen use efficiency, and larger seed size) were correlated with
      variation in bacterial community composition and enzyme activity. These results
      indicate that plant evolutionary history and life history strategy influence
      rhizosphere bacterial community composition and activity. Thus, incorporating
      phylogenetic or functional diversity into crop rotations may be a tool to
      manipulate plant-microbe interactions in agricultural systems.

PMID- 29321764
TI  - Fecal Microbiota Transplantation, Commensal Escherichia coli and Lactobacillus
      johnsonii Strains Differentially Restore Intestinal and Systemic Adaptive Immune
      Cell Populations Following Broad-spectrum Antibiotic Treatment.
AB  - The essential role of the intestinal microbiota in the well-functioning of host
      immunity necessitates the investigation of species-specific impacts on this
      interplay. Aim of this study was to examine the ability of defined Gram-positive
      and Gram-negative intestinal commensal bacterial species, namely Escherichia coli
      and Lactobacillus johnsonii, respectively, to restore immune functions in mice
      that were immunosuppressed by antibiotics-induced microbiota depletion.
      Conventional mice were subjected to broad-spectrum antibiotic treatment for 8
      weeks and perorally reassociated with E. coli, L. johnsonii or with a complex
      murine microbiota by fecal microbiota transplantation (FMT). Analyses at days (d)
      7 and 28 revealed that immune cell populations in the small and large intestines,
      mesenteric lymph nodes and spleens of mice were decreased after antibiotic
      treatment but were completely or at least partially restored upon FMT or by
      recolonization with the respective bacterial species. Remarkably, L. johnsonii
      recolonization resulted in the highest CD4+ and CD8+ cell numbers in the small
      intestine and spleen, whereas neither of the commensal species could stably
      restore those cell populations in the colon until d28. Meanwhile less efficient
      than FMT, both species increased the frequencies of regulatory T cells and
      activated dendritic cells and completely restored intestinal memory/effector T
      cell populations at d28. Furthermore, recolonization with either single species
      maintained pro- and anti-inflammatory immune functions in parallel. However, FMT
      could most effectively recover the decreased frequencies of cytokine producing
      CD4+ lymphocytes in mucosal and systemic compartments. E. coli recolonization
      increased the production of cytokines such as TNF, IFN-gamma, IL-17, and IL-22,
      particularly in the small intestine. Conversely, only L. johnsonii recolonization
      maintained colonic IL-10 production. In summary, FMT appears to be most efficient
      in the restoration of antibiotics-induced collateral damages to the immune
      system. However, defined intestinal commensals such as E. coli and L. johnsonii
      have the potential to restore individual functions of intestinal and systemic
      immunity. In conclusion, our data provide novel insights into the distinct role
      of individual commensal bacteria in maintaining immune functions during/following
      dysbiosis induced by antibiotic therapy thereby shaping host immunity and might
      thus open novel therapeutical avenues in conditions of perturbed microbiota
      composition.

PMID- 29321765
TI  - Microbiological and Geochemical Survey of CO2-Dominated Mofette and Mineral
      Waters of the Cheb Basin, Czech Republic.
AB  - The Cheb Basin (NW Bohemia, Czech Republic) is a shallow, neogene
      intracontinental basin. It is a non-volcanic region which features frequent
      earthquake swarms and large-scale diffuse degassing of mantle-derived CO2 at the
      surface that occurs in the form of CO2-rich mineral springs and wet and dry
      mofettes. So far, the influence of CO2 degassing onto the microbial communities
      has been studied for soil environments, but not for aquatic systems. We
      hypothesized, that deep-trenching CO2 conduits interconnect the subsurface with
      the surface. This admixture of deep thermal fluids should be reflected in
      geochemical parameters and in the microbial community compositions. In the
      present study four mineral water springs and two wet mofettes were investigated
      through an interdisciplinary survey. The waters were acidic and differed in terms
      of organic carbon and anion/cation concentrations. Element geochemical and
      isotope analyses of fluid components were used to verify the origin of the
      fluids. Prokaryotic communities were characterized through quantitative PCR and
      Illumina 16S rRNA gene sequencing. Putative chemolithotrophic, anaerobic and
      microaerophilic organisms connected to sulfur (e.g., Sulfuricurvum, Sulfurimonas)
      and iron (e.g., Gallionella, Sideroxydans) cycling shaped the core community.
      Additionally, CO2-influenced waters form an ecosystem containing many taxa that
      are usually found in marine or terrestrial subsurface ecosystems. Multivariate
      statistics highlighted the influence of environmental parameters such as pH, Fe2+
      concentration and conductivity on species distribution. The hydrochemical and
      microbiological survey introduces a new perspective on mofettes. Our results
      support that mofettes are either analogs or rather windows into the deep
      biosphere and furthermore enable access to deeply buried paleo-sediments.

PMID- 29321766
TI  - Untargeted Metabolomics Approach in Halophiles: Understanding the
      Biodeterioration Process of Building Materials.
AB  - The aim of the study was to explore the halophile metabolome in building
      materials using untargeted metabolomics which allows for broad metabolome
      coverage. For this reason, we used high-performance liquid chromatography
      interfaced to high-resolution mass spectrometry (HPLC/HRMS). As an alternative to
      standard microscopy techniques, we introduced pioneering Coherent Anti-stokes
      Raman Scattering Microscopy (CARS) to non-invasively visualize microbial cells.
      Brick samples saturated with salt solution (KCl, NaCl (two salinity levels),
      MgSO4, Mg(NO3)2), were inoculated with the mixture of preselected halophilic
      microorganisms, i.e., bacteria: Halobacillus styriensis, Halobacillus
      naozhouensis, Halobacillus hunanensis, Staphylococcus succinus, Marinococcus
      halophilus, Virgibacillus halodenitryficans, and yeast: Sterigmatomyces
      halophilus and stored at 28 degrees C and 80% relative humidity for a year.
      Metabolites were extracted directly from the brick samples and measured via
      HPLC/HRMS in both positive and negative ion modes. Overall, untargeted
      metabolomics allowed for discovering the interactions of halophilic
      microorganisms with buildings materials which together with CARS microscopy
      enabled us to elucidate the biodeterioration process caused by halophiles. We
      observed that halophile metabolome was differently affected by different salt
      solutions. Furthermore, we found indications for haloadaptive strategies and
      degradation of brick samples due to microbial pigment production as a salt stress
      response. Finally, we detected changes in lipid content related to changes in the
      structure of phospholipid bilayers and membrane fluidity.

PMID- 29321767
TI  - Diversity of Microbial Communities and Quantitative Chemodiversity in Layers of
      Marine Sediment Cores from a Causeway (Kaichu-Doro) in Okinawa Island, Japan.
AB  - Microbial community diversity and chemodiversity were investigated in marine
      sediments adjacent to the Okinawan "Kaichu-Doro" Causeway, which was constructed
      46 years ago to connect a group of four islands (Henza-jima, Miyagi-jima, Ikei
      jima, Hamahiga-jima) to the Okinawan main island. This causeway was not built on
      pilings, but by land reclamation; hence, it now acts as a long, thin peninsula.
      The construction of this causeway was previously shown to have influenced the
      surrounding marine ecosystem, causing ecosystem fragmentation and loss of water
      circulation. In this study, we collected sediment cores (n = 10) from five paired
      sites in 1 m water depths. Each pair of sites consisted of one site each on the
      immediate north and south sides of the causeway. Originally the members of each
      pair were much closer to each other (<150 m) than to other pairs, but now the
      members of each pair are isolated by the causeway. Each core was 60-80 cm long
      and was divided into 15-cm layers. We examined the vertical diversity of
      microbial communities and chemical compounds to determine the correlation between
      chemodiversity and microbial communities among marine sediment cores and layers.
      Principal coordinate analyses (PCoA) of detected compounds and of bacterial and
      archaeal operational taxonomic units (OTUs) revealed that the north and south
      sides of the causeway are relatively isolated, with each side having unique
      microbial OTUs. Additionally, some bacterial families (e.g.,
      Acidaminobacteraceae, Rhizobiaceae, and Xanthomonadaceae) were found only on the
      south side of Kaichu-Doro. Interestingly, we found that the relative abundance of
      OTUs for some microbial families increased from top to bottom, but this was
      reversed in some other families. We conclude that the causeway has altered
      microbial community composition and metabolite profiles in marine sediments.

PMID- 29321768
TI  - Repurposing and Revival of the Drugs: A New Approach to Combat the Drug Resistant
      Tuberculosis.
AB  - Emergence of drug resistant tuberculosis like multi drug resistant tuberculosis
      (MDR-TB), extensively drug-resistant tuberculosis (XDR-TB) and totally drug
      resistant tuberculosis (TDR-TB) has created a new challenge to fight against
      these bad bugs of Mycobacterium tuberculosis. Repurposing and revival of the
      drugs are the new trends/options to combat these worsen situations of
      tuberculosis in the antibiotics resistance era or in the situation of global
      emergency. Bactericidal and synergistic effect of repurposed/revived drugs along
      with the latest drugs bedaquiline and delamanid used in the treatment of MDR-TB,
      XDR-TB, and TDR-TB might be the choice for future promising combinatorial
      chemotherapy against these bad bugs.

PMID- 29321769
TI  - Analysis of Piscirickettsia salmonis Metabolism Using Genome-Scale
      Reconstruction, Modeling, and Testing.
AB  - Piscirickettsia salmonis is an intracellular bacterial fish pathogen that causes
      piscirickettsiosis, a disease with highly adverse impact in the Chilean salmon
      farming industry. The development of effective treatment and control methods for
      piscireckttsiosis is still a challenge. To meet it the number of studies on P.
      salmonis has grown in the last couple of years but many aspects of the pathogen's
      biology are still poorly understood. Studies on its metabolism are scarce and
      only recently a metabolic model for reference strain LF-89 was developed. We
      present a new genome-scale model for P. salmonis LF-89 with more than twice as
      many genes as in the previous model and incorporating specific elements of the
      fish pathogen metabolism. Comparative analysis with models of different bacterial
      pathogens revealed a lower flexibility in P. salmonis metabolic network. Through
      constraint-based analysis, we determined essential metabolites required for its
      growth and showed that it can benefit from different carbon sources tested
      experimentally in new defined media. We also built an additional model for strain
      A1-15972, and together with an analysis of P. salmonis pangenome, we identified
      metabolic features that differentiate two main species clades. Both models
      constitute a knowledge-base for P. salmonis metabolism and can be used to guide
      the efficient culture of the pathogen and the identification of specific drug
      targets.

PMID- 29321770
TI  - The Atypical Guanylate Kinase MoGuk2 Plays Important Roles in Asexual/Sexual
      Development, Conidial Septation, and Pathogenicity in the Rice Blast Fungus.
AB  - Guanylate kinases (GKs), which convert guanosine monophosphate into guanosine
      diphosphate (GDP), are important for growth and mannose outer chain elongation of
      cell wall N-linked glycoproteins in yeast. Here, we identified the ortholog of
      Saccharomyces cerevisiae GK Guk1, named MoGuk1 and a novel family of fungal GKs
      MoGuk2 in the rice blast fungus Magnaporthe oryzae. MoGuk1 contains 242 aa with
      an C-terminal GuKc domain that very similar to yeast Guk1. MoGuk2 contains 810
      amino acids with a C-terminal GuKc domain and an additional N-terminal efThoc1
      domain. Expression of either MoGuk1 or MoGuk2 in heterozygote yeast guk1 mutant
      could increase its GDP level. To investigate the biological role of MoGuk1 and
      MoGuk2 in M. oryzae, the gene replacement vectors were constructed. We obtained
      the DeltaMoguk2 but not DeltaMoguk1 mutant by screening over 1,000 transformants,
      indicating MoGuk1 might be essential for M. oryzae. The DeltaMoguk2 mutant showed
      weak reductions in vegetative growth, conidial germination, appressorial
      formation, and appressorial turgor, and showed significant reductions in
      sporulation and pathogenicity. Moreover, the DeltaMoguk2 mutant failed to produce
      perithecia and was sensitive to neomycin and a mixture of neomycin-tunicamycin.
      Exogenous GDP and ATP partially rescued the defects in conidial germination,
      appressorial formation, and infectious growth of the mutant. Further analysis
      revealed that intracellular GDP and GTP level was decreased, and GMP level was
      increased in the mutant, suggesting that MoGuk2 exhibits enzymatic activity.
      Structural analysis proved that the efThoc1, GuKc, and P-loop domains are
      essential for the full function of MoGuk2. Taken together, our data suggest that
      the guanylate kinase MoGuk2 is involved in the de novo GTP biosynthesis pathway
      and is important for infection-related morphogenesis in the rice blast fungus.

PMID- 29321771
TI  - Dual Regulation of Bacillus subtilis kinB Gene Encoding a Sporulation Trigger by
      SinR through Transcription Repression and Positive Stringent Transcription
      Control.
AB  - It is known that transcription of kinB encoding a trigger for Bacillus subtilis
      sporulation is under repression by SinR, a master repressor of biofilm formation,
      and under positive stringent transcription control depending on the adenine
      species at the transcription initiation nucleotide (nt). Deletion and base
      substitution analyses of the kinB promoter (P kinB ) region using lacZ fusions
      indicated that either a 5-nt deletion (Delta5, nt -61/-57, +1 is the
      transcription initiation nt) or the substitution of G at nt -45 with A (G-45A)
      relieved kinB repression. Thus, we found a pair of SinR-binding consensus
      sequences (GTTCTYT; Y is T or C) in an inverted orientation (SinR-1) between nt 
      57/-42, which is most likely a SinR-binding site for kinB repression. This relief
      from SinR repression likely requires SinI, an antagonist of SinR. Surprisingly,
      we found that SinR is essential for positive stringent transcription control of P
      kinB . Electrophoretic mobility shift assay (EMSA) analysis indicated that SinR
      bound not only to SinR-1 but also to SinR-2 (nt -29/-8) consisting of another
      pair of SinR consensus sequences in a tandem repeat arrangement; the two
      sequences partially overlap the '-35' and '-10' regions of P kinB . Introduction
      of base substitutions (T-27C C-26T) in the upstream consensus sequence of SinR-2
      affected positive stringent transcription control of P kinB , suggesting that
      SinR binding to SinR-2 likely causes this positive control. EMSA also implied
      that RNA polymerase and SinR are possibly bound together to SinR-2 to form a
      transcription initiation complex for kinB transcription. Thus, it was suggested
      in this work that derepression of kinB from SinR repression by SinI induced by
      Spo0A~P and occurrence of SinR-dependent positive stringent transcription control
      of kinB might induce effective sporulation cooperatively, implying an intimate
      interplay by stringent response, sporulation, and biofilm formation.

PMID- 29321772
TI  - Simulation of Escherichia coli Dynamics in Biofilms and Submerged Colonies with
      an Individual-Based Model Including Metabolic Network Information.
AB  - Clustered microbial communities are omnipresent in the food industry, e.g., as
      colonies of microbial pathogens in/on food media or as biofilms on food
      processing surfaces. These clustered communities are often characterized by
      metabolic differentiation among their constituting cells as a result of
      heterogeneous environmental conditions in the cellular surroundings. This paper
      focuses on the role of metabolic differentiation due to oxygen gradients in the
      development of Escherichia coli cell communities, whereby low local oxygen
      concentrations lead to cellular secretion of weak acid products. For this reason,
      a metabolic model has been developed for the facultative anaerobe E. coli
      covering the range of aerobic, microaerobic, and anaerobic environmental
      conditions. This metabolic model is expressed as a multiparametric programming
      problem, in which the influence of low extracellular pH values and the presence
      of undissociated acid cell products in the environment has been taken into
      account. Furthermore, the developed metabolic model is incorporated in MICRODIMS,
      an in-house developed individual-based modeling framework to simulate microbial
      colony and biofilm dynamics. Two case studies have been elaborated using the
      MICRODIMS simulator: (i) biofilm growth on a substratum surface and (ii)
      submerged colony growth in a semi-solid mixed food product. In the first case
      study, the acidification of the biofilm environment and the emergence of typical
      biofilm morphologies have been observed, such as the mushroom-shaped structure of
      mature biofilms and the formation of cellular chains at the exterior surface of
      the biofilm. The simulations show that these morphological phenomena are
      respectively dependent on the initial affinity of pioneer cells for the
      substratum surface and the cell detachment process at the outer surface of the
      biofilm. In the second case study, a no-growth zone emerges in the colony center
      due to a local decline of the environmental pH. As a result, cellular growth in
      the submerged colony is limited to the colony periphery, implying a linear
      increase of the colony radius over time. MICRODIMS has been successfully used to
      reproduce complex dynamics of clustered microbial communities.

PMID- 29321773
TI  - The Potential of Donor T-Cell Repertoires in Neoantigen-Targeted Cancer
      Immunotherapy.
AB  - T cells can recognize peptides encoded by mutated genes, but analysis of tumor
      infiltrating lymphocytes suggests that very few neoantigens spontaneously elicit
      T-cell responses. This may be an important reason why immune checkpoint
      inhibitors are mainly effective in tumors with a high mutational burden. Reasons
      for clinically insufficient responses to neoantigens might be inefficient
      priming, inhibition, or deletion of the cognate T cells. Responses can be
      dramatically improved by cancer immunotherapy such as checkpoint inhibition, but
      often with temporary effects. By contrast, T cells from human leukocyte antigen
      (HLA)-matched donors can cure diseases such as chronic myeloid leukemia. The
      therapeutic effect is mediated by donor T cells recognizing polymorphic peptides
      for which the donor and patient are disparate, presented on self-HLA. Donor T
      cell repertoires are unbiased by the immunosuppressive environment of the tumor.
      A recent study demonstrated that T cells from healthy individuals are able to
      respond to neoantigens that are ignored by tumor-infiltrating T cells of melanoma
      patients. In this review, we discuss possible reasons why neoantigens escape host
      T cells and how these limitations may be overcome by utilization of donor-derived
      T-cell repertoires to facilitate rational design of neoantigen-targeted
      immunotherapy.

PMID- 29321774
TI  - Amino Acid Sensing via General Control Nonderepressible-2 Kinase and
      Immunological Programming.
AB  - Metabolic adaptation to the changing nutrient levels in the cellular
      microenvironment plays a decisive role in the maintenance of homeostasis.
      Eukaryotic cells are equipped with nutrient sensors, which sense the fluctuating
      nutrients levels and accordingly program the cellular machinery to mount an
      appropriate response. Nutrients including amino acids play a vital role in
      maintaining cellular homeostasis. Therefore, over the evolution, different
      species have developed diverse mechanisms to detect amino acids abundance or
      scarcity. Immune responses have been known to be closely associated with the
      cellular metabolism especially amino acid sensing pathway, which influences
      innate as well as adaptive immune-effector functions. Thus, exploring the cross
      talk between amino acid sensing mechanisms and immune responses in disease as
      well as in normal physiological conditions might open up avenues to explore how
      this association can be exploited to tailor immunological functions toward the
      design of better therapeutics for controlling metabolic diseases. In this review,
      we discuss the advances in the knowledge of various amino acid sensing pathways
      including general control nonderepressible-2 kinase in the control of
      inflammation and metabolic diseases.

PMID- 29321776
TI  - Structure-Activity Relationship of Plesiomonas shigelloides Lipid A to the
      Production of TNF-alpha, IL-1beta, and IL-6 by Human and Murine Macrophages.
AB  - Plesiomonas shigelloides is a Gram-negative bacterium that is associated with
      diarrheal disease in humans. Lipopolysaccharide (LPS) is the main surface antigen
      and virulence factor of this bacterium. The lipid A (LA) moiety of LPS is the
      main region recognized by target cells of immune system. Here, we evaluated the
      biological activities of P. shigelloides LA for their abilities to induce the
      productions of proinflammatory cytokines (TNF-alpha, IL-1beta, and IL-6) by human
      and murine macrophages [THP-1 macrophages and immortalized murine bone marrow
      derived macrophages (iBMDM)]. Four native P. shigelloides LA preparations
      differing in their phosphoethanolamine (PEtn) substitution, length, number, and
      saturation of fatty acids were compared with Escherichia coli O55 LA. The
      bisphosphorylated, hexaacylated, and asymmetric forms of the P. shigelloides and
      E. coli LA molecules had similar activities in human and murine macrophages,
      indicating that shortening of the acyl chains in P. shigelloides LA had no effect
      on its in vitro activities. The PEtn decoration also had no impact on the
      interaction with the toll-like receptor 4/MD-2 receptor complex. The
      heptaacylated form of P. shigelloides LA decorated with 16:0 exhibited strong
      effect on proinflammatory activity, significantly decreasing the levels of all
      tested cytokines in both murine and human macrophages. Our results revealed that
      despite the presence of shorter acyl chains and an unsaturated acyl residue
      (16:1), the bisphosphorylated, hexaacylated, and asymmetric forms of P.
      shigelloides LA represent highly immunostimulatory structures.

PMID- 29321775
TI  - Myosin 1g Contributes to CD44 Adhesion Protein and Lipid Rafts Recycling and
      Controls CD44 Capping and Cell Migration in B Lymphocytes.
AB  - Cell migration and adhesion are critical for immune system function and involve
      many proteins, which must be continuously transported and recycled in the cell.
      Recycling of adhesion molecules requires the participation of several proteins,
      including actin, tubulin, and GTPases, and of membrane components such as
      sphingolipids and cholesterol. However, roles of actin motor proteins in adhesion
      molecule recycling are poorly understood. In this study, we identified myosin 1g
      as one of the important motor proteins that drives recycling of the adhesion
      protein CD44 in B lymphocytes. We demonstrate that the lack of Myo1g decreases
      the cell-surface levels of CD44 and of the lipid raft surrogate GM1. In cells
      depleted of Myo1g, the recycling of CD44 was delayed, the delay seems to be
      caused at the level of formation of recycling complex and entry into recycling
      endosomes. Moreover, a defective lipid raft recycling in Myo1g-deficient cells
      had an impact both on the capping of CD44 and on cell migration. Both processes
      required the transportation of lipid rafts to the cell surface to deliver
      signaling components. Furthermore, the extramembrane was essential for cell
      expansion and remodeling of the plasma membrane topology. Therefore, Myo1g is
      important during the recycling of lipid rafts to the membrane and to the
      accompanied proteins that regulate plasma membrane plasticity. Thus, Myosin 1g
      contributes to cell adhesion and cell migration through CD44 recycling in B
      lymphocytes.

PMID- 29321777
TI  - How Endothelial Cells Adapt Their Metabolism to Form Vessels in Tumors.
AB  - Endothelial cells (ECs) line blood vessels, i.e., vital conduits for oxygen and
      nutrient delivery to distant tissues. While mostly present as quiescent "phalanx"
      cells throughout adult life, ECs can rapidly switch to a migratory "tip" cell and
      a proliferative "stalk" cell, and sprout into avascular tissue to form new blood
      vessels. The angiogenic switch has long been considered to be primarily
      orchestrated by the activity of angiogenic molecules. However, recent evidence
      illustrates an instrumental role of cellular metabolism in vessel sprouting,
      whereby ECs require specific metabolic adaptations to grow. Here, we overview the
      emerging picture that tip, stalk, and phalanx cells have distinct metabolic
      signatures and discuss how these signatures can become deregulated in
      pathological conditions, such as in cancer.

PMID- 29321778
TI  - Immunosuppressive Effect of B7-H4 Pathway in a Murine Systemic Lupus
      Erythematosus Model.
AB  - B7-H4, one of the co-stimulatory molecules of the B7 family, has been shown to
      play an important role in negatively regulating the adaptive immune response by
      inhibiting the proliferation, activation, and cytokine production of T cells. In
      this study, we investigate the role of B7-H4 in development of systemic lupus
      erythematosus (SLE). We investigated a murine model of SLE using transfer of bone
      marrow-derived dendritic cells (BMDCs) that were incubated with activated
      syngeneic lymphocyte-derived DNA. The recipient mouse produced anti-ds-DNA
      antibodies as well as displayed splenomegaly and lymphadenopathy as shown by
      significantly increased weights, and the kidneys showed lupus-like pathological
      changes include urine protein and glomerulonephritis with hyperplasia in
      glomeruli and increased mesangial cells and vasculitis with perivascular cell
      infiltration, glomerular deposition of IgG and complement C3. We showed that B7
      H4 deficiency in BMDCs could cause greater production of anti-ds-DNA antibodies
      in transferred mice, and the lymph tissue swelling and the kidney lesions were
      also exacerbated with B7-H4 deficiency. Treatment with a B7-H4 antagonist
      antibody also aggravated the lupus model. Conversely, B7-H4 Ig alleviated the
      lupus manifestations. Therefore, we conclude that B7-H4 is a negative check point
      for the development of SLE in this murine model. These results suggest that this
      approach may have a clinical potential in treating human SLE.

PMID- 29321779
TI  - Exercise Prevents Enhanced Postoperative Neuroinflammation and Cognitive Decline
      and Rectifies the Gut Microbiome in a Rat Model of Metabolic Syndrome.
AB  - Introduction: Postoperative cognitive decline (PCD) can affect in excess of 10%
      of surgical patients and can be considerably higher with risk factors including
      advanced age, perioperative infection, and metabolic conditions such as obesity
      and insulin resistance. To define underlying pathophysiologic processes, we used
      animal models including a rat model of metabolic syndrome generated by breeding
      for a trait of low aerobic exercise tolerance. After 35 generations, the low
      capacity runner (LCR) rats differ 10-fold in their aerobic exercise capacity from
      high capacity runner (HCR) rats. The LCR rats respond to surgical procedure with
      an abnormal phenotype consisting of exaggerated and persistent PCD and failure to
      resolve neuroinflammation. We determined whether preoperative exercise can
      rectify the abnormal surgical phenotype. Materials and methods: Following
      institutional approval of the protocol each of male LCR and male HCR rats were
      randomly assigned to four groups and subjected to isoflurane anesthesia and tibia
      fracture with internal fixation (surgery) or anesthesia alone (sham surgery) and
      to a preoperative exercise regimen that involved walking for 10 km on a treadmill
      over 6 weeks (exercise) or being placed on a stationary treadmill (no exercise).
      Feces were collected before and after exercise for assessment of gut microbiome.
      Three days following surgery or sham surgery the rats were tested for ability to
      recall a contextual aversive stimulus in a trace fear conditioning paradigm.
      Thereafter some rats were euthanized and the hippocampus harvested for analysis
      of inflammatory mediators. At 3 months, the remainder of the rats were tested for
      memory recall by the probe test in a Morris Water Maze. Results: Postoperatively,
      LCR rats exhibited exaggerated cognitive decline both at 3 days and at 3 months
      that was prevented by preoperative exercise. Similarly, LCR rats had excessive
      postoperative neuroinflammation that was normalized by preoperative exercise.
      Diversity of the gut microbiome in the LCR rats improved after exercise.
      Discussion: Preoperative exercise eliminated the metabolic syndrome risk for the
      abnormal surgical phenotype and was associated with a more diverse gut
      microbiome. Prehabilitation with exercise should be considered as a possible
      intervention to prevent exaggerated and persistent PCD in high-risk settings.

PMID- 29321780
TI  - Granulocytes: New Members of the Antigen-Presenting Cell Family.
AB  - Granulocytes, the most abundant types of leukocytes, are the first line of
      defense against pathogen invasion. However, the plasticity and diversity of
      granulocytes have been increasingly revealed, especially with regard to their
      versatile functions in orchestrating adaptive immune responses. A substantial
      body of recent evidence demonstrates that granulocytes can acquire the function
      as antigen-presenting cells under pathological or inflammatory conditions. In
      addition, they can acquire surface expression of MHC class II and costimulatory
      molecules as well as T cell stimulatory behavior when cultured with selected
      cytokines. The classic view of granulocytes as terminally differentiated, short
      lived phagocytes is therefore changing to phenotypically and functionally
      heterogeneous cells that are engaged in cross-talk with other leukocyte
      populations and provide an additional link between innate and adaptive immunity.
      In this brief review, we summarize the current knowledge on the antigen
      presenting capacity of granulocyte subsets (neutrophils, eosinophils, and
      basophils). Underlying mechanisms, relevant physiological significance and
      potential controversies are also discussed.

PMID- 29321781
TI  - Mucosal Mesenchymal Cells: Secondary Barrier and Peripheral Educator for the Gut
      Immune System.
AB  - Stromal connective tissue contains mesenchymal cells, including fibroblasts and
      myofibroblasts, which line the tissue structure. However, it has been identified
      that the function of mesenchymal cells is not just structural-they also play
      critical roles in the creation and regulation of intestinal homeostasis. Thus,
      mucosal mesenchymal cells instruct intestinal immune cell education (or
      peripheral immune education) and epithelial cell differentiation thereby shaping
      the local environment of the mucosal immune system. Malfunction of the
      mesenchymal cell-mediated instruction system (e.g., fibrosis) leads to
      pathological conditions such as intestinal stricture.

PMID- 29321782
TI  - Functional Characterization of the Disease-Associated N-Terminal Complement
      Factor H Mutation W198R.
AB  - Dysregulation of the complement alternative pathway is involved in the
      pathogenesis of several diseases, including the kidney diseases atypical
      hemolytic uremic syndrome (aHUS) and C3 glomerulopathy (C3G). In a patient,
      initially diagnosed with chronic glomerulonephritis, possibly C3G, and who 6
      years later had an episode of aHUS, a heterozygous missense mutation leading to a
      tryptophan to arginine exchange (W198R) in the factor H (FH) complement control
      protein (CCP) 3 domain has previously been identified. The aim of this study was
      to clarify the functional relevance of this mutation. To this end, wild-type (FH1
      4WT) and mutant (FH1-4W198R) CCPs 1-4 of FH were expressed as recombinant
      proteins. The FH1-4W198R mutant showed decreased C3b binding compared with FH1
      4WT. FH1-4W198R had reduced cofactor and decay accelerating activity compared
      with the wild-type protein. Hemolysis assays demonstrated impaired capacity of
      FH1-4W198R to protect rabbit erythrocytes from human complement-mediated lysis,
      and also to prevent lysis of sheep erythrocytes in human serum induced by a
      monoclonal antibody binding in FH CCP5 domain, compared with that of FH1-4WT.
      Thus, the FH W198R exchange results in impaired complement alternative pathway
      regulation. The heterozygous nature of this mutation in the index patient may
      explain the manifestation of two diseases, likely due to different triggers
      leading to complement dysregulation in plasma or on cell surfaces.

PMID- 29321783
TI  - Differential Susceptibility to Infectious Respiratory Diseases between Males and
      Females Linked to Sex-Specific Innate Immune Inflammatory Response.
AB  - It is widely acknowledged that males and females exhibit contrasting degrees of
      susceptibility to infectious and non-infectious inflammatory diseases. This is
      particularly observed in respiratory diseases where human males are more likely
      to be affected by infection-induced acute inflammations compared to females. The
      type and magnitude of the innate immune inflammatory response play a cardinal
      role in this sex bias. Animal models mimicking human respiratory diseases have
      been used to address the biological factors that could explain the distinct
      outcomes. In this review, we focus on our current knowledge about experimental
      studies investigating sex-specific differences in infection-induced respiratory
      diseases and we provide an update on the most important innate immune mechanisms
      that could explain sex bias of the inflammatory response. We also discuss whether
      conclusions drawn from animal studies could be relevant to human.

PMID- 29321784
TI  - Positive Feedback Regulation between Transglutaminase 2 and Toll-Like Receptor 4
      Signaling in Hepatic Stellate Cells Correlates with Liver Fibrosis Post
      Schistosoma japonicum Infection.
AB  - Liver fibrosis induced by Schistosoma japonicum (Sj) infection is characterized
      by the accumulation of extracellular matrix (ECM). The activated and
      differentiated hepatic stellate cells (HSCs) are the predominant ECM-producing
      cell type in the liver. Toll-like receptor (TLR) 4 pathway activation plays a key
      role in mice liver fibrosis models induced by alcohol, biliary ligation, and
      carbon tetrachloride 4. In this work, we found that TLR4 pathway activation
      correlated with the severity of liver fibrosis post Sj infection. The TLR4
      receptor inhibitor TAK242 reduced the extent of liver fibrosis. The increased
      expression of TLR4, alpha-smooth muscle actin (alpha-SMA), and cytoglobin was
      observed in the HSCs of mouse liver after Sj infection. In response to
      stimulation with either lipopolysaccharide or Sj's soluble egg antigen (SEA),
      high levels of TLR4 and alpha-SMA were induced in HSCs and were inhibited by
      TAK242 treatment. In previous work, we had reported that a high level of
      transglutaminase 2 (TGM2) is crucial for liver fibrosis post Sj infection.
      Herein, we found that TLR4 signaling also controlled Tgm2 expression. Inhibition
      of TGM2 activity by cystamine (CTM) in Sj-infected mice or in HSCs induced with
      all-trans-retinoic acid (ATRA) stimulation led to a lowered activation of TLR4
      signaling and a reduced alpha-SMA expression. These results were confirmed by
      downregulating the Tgm2 gene by specific siRNA. These observations implied the
      presence of a positive feedback regulation between TGM2 and TLR4 signaling in
      HSCs that correlated with liver fibrosis post Sj infection. This novel connection
      between TGM2 and TLR4 pathway activation in liver fibrosis induced by Sj
      infection enhances our understanding of liver diseases.

PMID- 29321786
TI  - Arabidopsis Basic Helix-Loop-Helix 34 (bHLH34) Is Involved in Glucose Signaling
      through Binding to a GAGA Cis-Element.
AB  - The modulation of glucose (Glc) homeostasis and signaling is crucial for plant
      growth and development. Nevertheless, the molecular signaling mechanism by which
      a plant senses a cellular Glc level and coordinates the expression of Glc
      responsive genes is still incompletely understood. Previous studies have shown
      that Arabidopsis thaliana plasma membrane Glc-responsive regulator (AtPGR) is a
      component of the Glc-responsive pathway. Here, we demonstrated that a
      transcription factor bHLH34 binds to 5'-GAGA-3' element of the promoter region of
      AtPGR in vitro, and activates beta-glucuronidase (GUS) activity upon Glc
      treatment in AtPGR promoter-GUS transgenic plants. Gain- and loss-of-function
      analyses suggested that the bHLH34 involved in the responses to not only Glc, but
      also abscisic acid (ABA) and salinity. These results suggest that bHLH34
      functions as a transcription factor in the Glc-mediated stress responsive pathway
      as well as an activator of AtPGR transcription. Furthermore, genetic experiments
      revealed that in Glc response, the functions of bHLH34 are different from that of
      a bHLH104, a homolog of bHLH34. Collectively, our findings indicate that bHLH34
      is a positive regulator of Glc, and may affect ABA or salinity response, whereas
      bHLH104 is a negative regulator and epistatic to bHLH34 in the Glc response.

PMID- 29321785
TI  - miR160 and miR166/165 Contribute to the LEC2-Mediated Auxin Response Involved in
      the Somatic Embryogenesis Induction in Arabidopsis.
AB  - MicroRNAs are non-coding small RNA molecules that are involved in the post
      transcriptional regulation of the genes that control various developmental
      processes in plants, including zygotic embryogenesis (ZE). miRNAs are also
      believed to regulate somatic embryogenesis (SE), a counterpart of the ZE that is
      induced in vitro in plant somatic cells. However, the roles of specific miRNAs in
      the regulation of the genes involved in SE, in particular those encoding
      transcription factors (TFs) with an essential function during SE including LEAFY
      COTYLEDON2 (LEC2), remain mostly unknown. The aim of the study was to reveal the
      function of miR165/166 and miR160 in the LEC2-controlled pathway of SE that is
      induced in in vitro cultured Arabidopsis explants.In ZE, miR165/166 controls the
      PHABULOSA/PHAVOLUTA (PHB/PHV) genes, which are the positive regulators of LEC2,
      while miR160 targets the AUXIN RESPONSE FACTORS (ARF10, ARF16, ARF17) that
      control the auxin signaling pathway, which plays key role in LEC2-mediated SE. We
      found that a deregulated expression/function of miR165/166 and miR160 resulted in
      a significant accumulation of auxin in the cultured explants and the spontaneous
      formation of somatic embryos. Our results show that miR165/166 might contribute
      to SE induction via targeting PHB, a positive regulator of LEC2 that controls
      embryogenic induction via activation of auxin biosynthesis pathway (Wojcikowska
      et al., 2013). Similar to miR165/166, miR160 was indicated to control SE
      induction through auxin-related pathways and the negative impact of miR160 on
      ARF10/ARF16/ARF17 was shown in an embryogenic culture. Altogether, the results
      suggest that the miR165/166- and miR160-node contribute to the LEC2-mediated
      auxin-related pathway of embryogenic transition that is induced in the somatic
      cells of Arabidopsis. A model summarizing the suggested regulatory interactions
      between the miR165/166-PHB and miR160-ARF10/ARF16/ARF17 nodes that control SE
      induction in Arabidopsis was proposed.

PMID- 29321788
TI  - Effects of Soil Water Deficit on Insecticidal Protein Expression in Boll Shells
      of Transgenic Bt Cotton and the Mechanism.
AB  - This study was conducted to investigate the effects of soil water deficit on
      insecticidal protein expression in boll shells of cotton transgenic for a Bt
      gene. In 2014, Bt cotton cultivars Sikang 1 (a conventional cultivar) and Sikang
      3 (a hybrid cultivar) were planted in pots and five soil water content treatments
      were imposed at peak boll stage: 15% (G1), 35% (G2), 40% (G3), 60% (G4), and 75%
      field capacity (CK), respectively. Four treatments (G2, G3, G4, and CK) were
      repeated in 2015 in the field. Results showed that the insecticidal protein
      content of boll shells decreased with increasing water deficit. Compared with CK,
      boll shell insecticidal protein content decreased significantly when soil water
      content was below 60% of maximum water holding capacity for Sikang 1 and Sikang
      3. However, increased Bt gene expression was observed when boll shell
      insecticidal protein content was significantly reduced. Activity assays of key
      enzymes in nitrogen metabolism showed that boll shell protease and peptidase
      increased but nitrogen reductase and glutamic-pyruvic transaminase (GPT)
      decreased. Insecticidal protein content exhibited significant positive
      correlation with nitrogen reductase and GPT activities; and significant negative
      correlation with protease and peptidase activities. These findings suggest that
      the decrease of insecticidal protein content associated with increasing water
      deficit was a net result of decreased synthesis and increased decomposition.

PMID- 29321787
TI  - Genetic Variation and Association Mapping of Seed-Related Traits in Cultivated
      Peanut (Arachis hypogaea L.) Using Single-Locus Simple Sequence Repeat Markers.
AB  - Cultivated peanut (Arachis hypogaea L.) is an allotetraploid (AABB, 2n = 4x =
      40), valued for its edible oil and digestible protein. Seed size and weight are
      important agronomical traits significantly influence the yield and nutritional
      composition of peanut. However, the genetic basis of seed-related traits remains
      ambiguous. Association mapping is a powerful approach for quickly and efficiently
      exploring the genetic basis of important traits in plants. In this study, a total
      of 104 peanut accessions were used to identify molecular markers associated with
      seed-related traits using 554 single-locus simple sequence repeat (SSR) markers.
      Most of the accessions had no or weak relationship in the peanut panel. The
      linkage disequilibrium (LD) decayed with the genetic distance of 1cM at the
      genome level and the LD of B subgenome decayed faster than that of the A
      subgenome. Large phenotypic variation was observed for four seed-related traits
      in the association panel. Using mixed linear model with population structure and
      kinship, a total of 30 significant SSR markers were detected to be associated
      with four seed-related traits (P < 1.81 * 10-3) in different environments, which
      explained 11.22-32.30% of the phenotypic variation for each trait. The marker
      AHGA44686 was simultaneously and repeatedly associated with seed length and
      hundred-seed weight in multiple environments with large phenotypic variance
      (26.23 ~ 32.30%). The favorable alleles of associated markers for each seed
      related trait and the optimal combination of favorable alleles of associated
      markers were identified to significantly enhance trait performance, revealing a
      potential of utilization of these associated markers in peanut breeding program.

PMID- 29321789
TI  - Photoperiodic Regulation of Growth-Dormancy Cycling through Induction of Multiple
      Bud-Shoot Barriers Preventing Water Transport into the Winter Buds of Norway
      Spruce.
AB  - Whereas long days (LDs) sustain shoot elongation, short days (SDs) induce growth
      cessation and formation of dormant buds in young individuals of a wide range of
      temperate and boreal tree species. In specific conifers, including Norway spruce,
      photoperiodic control of bud development is associated with the formation of a
      plate of thick-walled cells, denoted as the crown, at the base of the bud.
      Information about cellular characteristics of this crown region is limited. We
      aimed to test whether the crown region is an important SD-induced barrier
      ensuring dehydration of the developing winter bud by preventing water influx.
      Using microscopy and synchrotron techniques, we show here that under LD, cell
      walls in growing shoot tips had highly methyl-esterified homogalacturonan pectin.
      During SD-induced bud development, the homogalacturonan in the crown region was
      de-methyl-esterified, enabling Ca2+ binding and crosslinking, a process known to
      decrease cell wall water permeability by reducing pectin pore size. In addition,
      there was abundant callose deposition at plasmodesmata in the crown region, and
      xylem connections between the bud and the subtending shoot were blocked.
      Consistent with reduced water transport across the crown region into the bud,
      uptake of fluorescein in shoot tips was blocked at the base of the bud under SD.
      Upon transfer from SD to bud-break-inducing LD, these processes were reversed,
      and aquaporin transcript levels significantly increased in young stem tissue
      after 4 weeks under LD. These findings indicate that terminal bud development is
      associated with reduced water transport through decreased cell wall permeability
      and blocking of plasmodesmata and xylem connections in the crown structure. This
      provides further understanding of the regulatory mechanism for growth-dormancy
      cycling in coniferous tree species such as Norway spruce.

PMID- 29321790
TI  - An Advanced Backcross Population through Synthetic Octaploid Wheat as a "Bridge":
      Development and QTL Detection for Seed Dormancy.
AB  - The seed dormancy characteristic is regarded as one of the most critical factors
      for pre-harvest sprouting (PHS) resistance. As a wild wheat relative species,
      Aegilops tauschii is a potential genetic resource for improving common wheat. In
      this study, an advanced backcross population (201 strains) containing only Ae.
      tauschii segments was developed by means of synthetic octaploid wheat (hexaploid
      wheat Zhoumai 18 * Ae. tauschii T093). Subsequently, seed dormancy rate (Dor) in
      the advanced backcross population was evaluated on the day 3, 5 and 7, in which 2
      major QTLs (QDor-2D and QDor-3D) were observed on chromosomes 2D and 3D with
      phenotypic variance explained values (PVEs) of 10.25 and 20.40%, respectively.
      Further investigation revealed significant correlation between QDor-3D and
      Tamyb10 gene, while no association was found between the former and TaVp1 gene,
      implying that QDor-3D site could be of closer position to Tamyb10. The obtained
      quantitative trait locus sites (QTLs) in this work could be applied to develop
      wheat cultivars with PHS resistance.

PMID- 29321791
TI  - Spatial Patterns of Species Diversity and Phylogenetic Structure of Plant
      Communities in the Tianshan Mountains, Arid Central Asia.
AB  - The Tianshan Mountains, located in arid Central Asia, have a humid climate and
      are biodiversity hotspots. Here, we aimed to clarify whether the pattern of
      species diversity and the phylogenetic structure of plant communities is affected
      by environmental variables and glacial refugia. In this study, plant community
      assemblies of 17 research sites with a total of 35 sample plots were investigated
      at the grassland/woodland boundaries on the Tianshan Mountains. Community
      phylogeny of these plant communities was constructed based on two plant DNA
      barcode regions. The indices of phylogenetic diversity and phylogenetic community
      structure were calculated for these sample plots. We first estimated the
      correlation coefficients between species richness (SR) and environmental
      variables as well as the presence of glacial refugia. We then mapped the
      significant values of indices of community phylogeny (PD, RPD, NRI, and NTI) to
      investigate the correlation between community phylogeny and environmental
      structure or macrozones in the study area. The results showed that a
      significantly higher value of SR was obtained for the refugial groups than for
      the colonizing groups (P < 0.05); presence of refugia and environmental variables
      were highly correlated to the pattern of variation in SR. Indices of community
      phylogeny were not significantly different between refugial and colonizing
      regions. Comparison with the humid western part showed that plant communities in
      the arid eastern part of the Tianshan Mountains tended to display more
      significant phylogenetic overdispersion. The variation tendency of the PhyloSor
      index showed that the increase in macro-geographical and environmental distance
      did not influence obvious phylogenetic dissimilarities between different sample
      plots. In conclusion, glacial refugia and environmental factors profoundly
      influenced the pattern of SR, but community phylogenetic structure was not
      affected by glacial refugia among different plant communities on the Tianshan
      Mountains. This pattern of community phylogenetic structure could have resulted
      from shared ancestry and species pool among these sample plots.

PMID- 29321792
TI  - The Challenge to Translate OMICS Data to Whole Plant Physiology: The Context
      Matters.

PMID- 29321793
TI  - Novel Genomic and Evolutionary Perspective of Cyanobacterial tRNAs.
AB  - Transfer RNA (tRNA) plays a central role in protein synthesis and acts as an
      adaptor molecule between an mRNA and an amino acid. A tRNA has an L-shaped clover
      leaf-like structure and contains an acceptor arm, D-arm, D-loop, anti-codon arm,
      anti-codon loop, variable loop, Psi-arm and Psi-loop. All of these arms and loops
      are important in protein translation. Here, we aimed to delineate the genomic
      architecture of these arms and loops in cyanobacterial tRNA. Studies from tRNA
      sequences from 61 cyanobacterial species showed that, except for few tRNAs
      (tRNAAsn, tRNALeu, tRNAGln, and tRNAMet), all contained a G nucleotide at the 1st
      position in the acceptor arm. tRNALeu and tRNAMet did not contain any conserved
      nucleotides at the 1st position whereas tRNAAsn and tRNAGln contained a conserved
      U1 nucleotide. In several tRNA families, the variable region also contained
      conserved nucleotides. Except for tRNAMet and tRNAGlu, all other tRNAs contained
      a conserved A nucleotide at the 1st position in the D-loop. The Psi-loop
      contained a conserved U1-U2-C3-x-A5-x-U7 sequence, except for tRNAGly, tRNAAla,
      tRNAVal, tRNAPhe, tRNAThr, and tRNAGln in which the U7 nucleotide was not
      conserved. However, in tRNAAsp, the U7 nucleotide was substituted with a C7
      nucleotide. Additionally, tRNAArg, tRNAGly, and tRNALys of cyanobacteria
      contained a group I intron within the anti-codon loop region. Maximum composite
      likelihood study on the transition/transversion of cyanobacterial tRNA revealed
      that the rate of transition was higher than the rate of transversion. An
      evolutionary tree was constructed to understand the evolution of cyanobacterial
      tRNA and analyses revealed that cyanobacterial tRNA may have evolved
      polyphyletically with high rate of gene loss.

PMID- 29321794
TI  - Individual Clinically Diagnosed with CHARGE Syndrome but with a Mutation in
      KMT2D, a Gene Associated with Kabuki Syndrome: A Case Report.
AB  - We report a Japanese female patient presenting with classic features of CHARGE
      syndrome, including choanal atresia, growth and development retardation, ear
      malformations, genital anomalies, multiple endocrine deficiency, and unilateral
      facial nerve palsy. She was clinically diagnosed with typical CHARGE syndrome,
      but genetic analysis using the TruSight One Sequence Panel revealed a germline
      heterozygous mutation in KMT2D with no pathogenic CHD7 alterations associated
      with CHARGE syndrome. Kabuki syndrome is a rare multisystem disorder
      characterized by five cardinal manifestations including typical facial features,
      skeletal anomalies, dermatoglyphic abnormalities, mild to moderate intellectual
      disability, and postnatal growth deficiency. Germline mutations in KMT2D underlie
      the molecular pathogenesis of 52-76% of patients with Kabuki syndrome. This is an
      instructive case that clearly represents a phenotypic overlap between Kabuki
      syndrome and CHARGE syndrome. It suggests the importance of considering the
      possibility of a diagnosis of Kabuki syndrome even if patients present with
      typical symptoms and meet diagnostic criteria of CHARGE syndrome. The case also
      emphasizes the impact of non-biased exhaustive genetic analysis by next
      generation sequencing in the genetic diagnosis of rare congenital disorders with
      atypical manifestations.

PMID- 29321795
TI  - Near-infrared spectroscopy in adult cardiac surgery: between conflicting results
      and unexpected uses.

PMID- 29321796
TI  - Heart rate variability: a new tool to predict complications in adult cardiac
      surgery.
AB  - Heart rate variability (HRV) refers to the variations between consecutive
      heartbeats, which depend on the continuous modulation of the sympathetic and
      parasympathetic branches of the autonomic nervous system. HRV has been shown to
      be effective as a predictor of risk after myocardial infarction and an early
      warning sign of diabetic neuropathy, and in the cardiology setting is now
      recognized to be a useful tool for risk-stratification after hospital admission
      and after discharge. Recent evidences suggest that HRV analysis might predict
      complications even in patients undergoing cardiac surgery, and the present review
      summarizes the importance of HRV analysis in adult cardiac surgery and the
      perspectives for HRV use in current clinical practice. Although future larger
      studies are warranted before HRV can be included into daily clinical practice in
      adult cardiac surgery, HRV is a novel tool which might detect autonomic
      instability in the early postoperative phase and during hospital stay, thus
      predicting or prompt-diagnosing many of the post-operative complications.

PMID- 29321797
TI  - Prediction model of in-hospital mortality in elderly patients with acute heart
      failure based on retrospective study.
AB  - Objectives: The aim of this study was to develop a clinical risk model that is
      predictive of in-hospital mortality in elderly patients hospitalized with acute
      heart failure (AHF). Methods: 2486 patients who were 60 years and older from
      intensive care units of Cardiology Department in the hospital were analyzed.
      Independent risk factors for in-hospital mortality were obtained by binary
      logistic regression and then used to establish the risk prediction score system
      (RPSS). The area under the curve (AUC) of receiver operator characteristic and C
      statistic test were adopted to assess the performance of RPSS and to compare with
      previous get with the guidelines-heart failure (GWTG-HF). Results: By binary
      logistic regression analysis, heart rate (OR: 1.043, 95% CI: 1.030-1.057, P <
      0.001), left ventricular ejection fraction (OR: 0.918, 95% CI: 0.833-0.966, P <
      0.001), pH value (OR: 0.001, 95% CI: 0.000-0.002, P < 0.001), renal dysfunction
      (OR: 0.120, 95% CI: 0.066-0.220, P < 0.001) and NT-pro BNP (OR: 3.463, 95% CI:
      1.870-6.413, P < 0.001) were independent risk factors of in-hospital mortality
      for elderly AHF patients. Additionally, RPSS, which was composed of all the above
      mentioned parameters, provided a better risk prediction than GWTG-THF (AUC: 0.873
      vs. 0.818, P = 0.016). Conclusions: Our risk prediction model, RPSS, provided a
      good prediction for in-hospital mortality in elderly patients with AHF.

PMID- 29321798
TI  - Impact of triple antithrombotic therapy in patients with acute coronary syndrome
      undergoing percutaneous coronary intervention in real-world practice.
AB  - Objective: The optimal antithrombotic regimen for patients on oral
      anticoagulation (OAC) after acute coronary syndrome (ACS) and percutaneous
      coronary intervention (PCI) remains debated. This study sought to evaluate the
      efficacy and safety of OAC plus clopidogrel with or without aspirin in a real
      world setting. Methods: We retrospectively analyzed data from an international,
      multi-center registry between 2003 and 2014 (n = 15,401). Patients with ACS and
      receiving OAC after PCI were screened. The composite primary endpoint was 1-year
      all-cause death, re-infarction, or severe bleeding. Results: The final analysis
      enrolled 642 patients including 62 patients (9.7%) with OAC and clopidogrel (dual
      therapy), and 580 patients (90.3%) with the combination of aspirin, OAC and
      clopidogrel (triple therapy). Patients on triple therapy were more often female
      and were more likely to have comorbidities. There was no significant difference
      regarding the primary end point between dual therapy with triple therapy patients
      [17.74% vs. 17.24%; unadjusted hazard ratio (HR): 1.035; 95% confidence interval
      (CI): 0.556-1.929; adjusted HR: 1.026; 95% CI: 0.544-1.937]. However, the re
      infarction rate was significantly higher in dual therapy than triple therapy
      patients (14.52% vs. 5.34%; unadjusted HR: 2.807; 95% CI: 1.329-5.928; adjusted
      HR: 2.333; 95% CI: 1.078-5.047). In addition, there was no difference between two
      regimes in all-cause death and severe bleeding. Conclusions: In real-life
      patients with ACS following PCI and with an indication of OAC, triple therapy was
      not associated with an increased rate of adverse outcomes compared to dual
      therapy. Moreover, it decreased risk of re-infarction and did not increase risk
      of severe bleeding.

PMID- 29321799
TI  - Independent and combined effects of environmental factors and miR-126, miR-143,
      and miR-145 on the risk of coronary heart disease.
AB  - Objective: To evaluate the effects of environmental factors and microRNAs
      (miRNAs) (miR-126, miR-143, and miR-145) on the risk of coronary heart disease
      (CHD). Methods: A frequency-matched case-control study (450 patients, 450
      controls) was conducted from April 2014 to December 2016 in Fuzhou City, China.
      Environmental factors were investigated using a self-administered questionnaire,
      and the expression levels of miR-126, miR-143, and miR-145 were determined by
      quantitative real-time Polymerase Chain Reaction (PCR) in peripheral blood
      mononuclear cells. Unconditional logistic regression models were used for
      statistical evaluation. Results: Alcohol consumption, high-salt diets, high
      intensity work, and lack of physical activity were significantly associated with
      increased CHD risk, whereas light diet was significantly associated with
      decreased risk. MiR-126, miR-143, and miR-145 were highly expressed in the CHD
      group compared with the control group. After adjustment for other environmental
      factors, unconditional logistic regression results revealed that miR-126, miR
      143, and depression were the independent risk factors of CHD, and light diet was
      the independent protective factor of CHD. Conclusions: Our data suggest that a
      family history of CHD, anxiety, and alcohol consumption was significantly
      associated with increased CHD risk, whereas light diet was significantly
      associated with decreased risk. Furthermore, miR-126 and miR-143 in combination
      with several risk factors, could play a joint role in the development of CHD.
      Therefore, it is necessary to manage patients with CHD in all directions and
      multiple level.

PMID- 29321802
TI  - Early prosthetic valve endocarditis after transcatheter aortic valve implantation
      with periannular complication.

PMID- 29321800
TI  - Vascular protection by high-density lipoprotein-associated sphingosine-1
      phosphate.
AB  - Epidemiological studies and animal experiments have consistently demonstrated
      cardiovascular protection by high-density lipoprotein (HDL). Findings from a
      growing number of studies further indicate that sphingosine-1-phosphate (S1P)
      mediates many of the beneficial effects of HDL on the cardiovascular system,
      including vasodilatation, angiogenesis, maintenance of endothelial barrier
      function, and protection against atherosclerosis and ischemia/reperfusion injury.
      In this review, we summarize the most recent literature investigating the effects
      of HDL-S1P on cardiovascular health and highlight potential opportunities for
      clinical translation of these findings.

PMID- 29321801
TI  - The role of immune abnormality in depression and cardiovascular disease.
AB  - Depression and cardiovascular disease (CVD) are both highly prevalent disorders,
      and some evidence shows that there is a 'vicious cycle' linking major depression
      and CVD. There is also growing evidence that immune abnormalities underpin the
      common pathophysiology of both CVD and major depression. The abnormalities
      include the following: abnormal levels of inflammatory markers, such as
      interleukin-6 (IL-6), interleukin-1beta (IL-1beta), tumor necrosis factor alpha
      (TNF-alpha) and interleukin-12 (IL-12); increased acute phase proteins, such as C
      reactive protein, fibrinogen and haptoglobin; and abnormal complement factors.
      The findings show that major depression and CVD patients have greater immune
      abnormalities, which may increase depressive symptoms and cardiovascular
      pathological changes, and that there may be a bidirectional relationship,
      therefore more prospective studies are needed to draw conclusions.

PMID- 29321803
TI  - The eyes are the window to the heart: one case of cardiac amyloidosis with eyelid
      swelling as the initial symptom.

PMID- 29321804
TI  - The relationship between NT-proBNP and Depression in Patients with Heart Failure.

PMID- 29321805
TI  - Simultaneous measurement of formic acid, methanol and ethanol in vitreous and
      blood samples of postmortem by headspace GC-FID.
AB  - Background: Formic acid (formate) is the main reason for toxicity and death
      through methanol poisoning. The simultaneous determination of methanol, ethanol,
      and formate in the body can help to discover the cause of death and is useful in
      the diagnosis of acute methanol poisoning. The measurement of formate is not yet
      available in Iran. With regard to the increasing rate of methanol poisoning and
      its related mortality in Iran, as well as the main role of formate in methanol
      poisoning, this study was designed to set up an analytical method for the
      concurrent determination of ethanol, methanol, and formate. Methods: Following
      the modification of a previously developed gas chromatography method, vitreous
      and blood samples of 43 postmortem cases with a history of methanol intoxication
      were collected over a period of 2 years at the Legal Medicine Organization of
      Mashhad. Thereafter, ethanol, methanol, and formate concentrations were measured
      by headspace GC/FID. Formate esterification was performed by the methylation of
      formate with sulfuric acid and methanol. In order to confirm the esterification
      method for the production of methyl formate, we used gas chromatography with a
      mass detector (GC/MS) because of its higher sensitivity and accuracy.
      Furthermore, the correlations between formate and methanol concentrations in
      blood and vitreous samples, and between formate and methanol were investigated.
      Results: A significant relationship was found only between methanol
      concentrations in blood and vitreous samples (P < 0.03). Conclusions: In
      postmortems, with the passage of time since alcohol ingestion, the measurement of
      only methanol concentration cannot determine the degree of toxicity or the cause
      of death. Therefore, using the present analytical method and measurement of
      formic acid, we can estimate the degree of toxicity and cause of death.

PMID- 29321806
TI  - Development of an in vitro pre-mRNA splicing assay using plant nuclear extract.
AB  - Background: Pre-mRNA splicing is an essential post-transcriptional process in all
      eukaryotes. In vitro splicing systems using nuclear or cytoplasmic extracts from
      mammalian cells, yeast, and Drosophila have provided a wealth of mechanistic
      insights into assembly and composition of the spliceosome, splicing regulatory
      proteins and mechanisms of pre-mRNA splicing in non-plant systems. The lack of an
      in vitro splicing system prepared from plant cells has been a major limitation in
      splicing research in plants. Results: Here we report an in vitro splicing assay
      system using plant nuclear extract. Several lines of evidence indicate that
      nuclear extract derived from Arabidopsis seedlings can convert pre-mRNA substrate
      (LHCB3) into a spliced product. These include: (1) generation of an RNA product
      that corresponds to the size of expected mRNA, (2) a junction-mapping assay using
      S1 nuclease revealed that the two exons are spliced together, (3) the reaction
      conditions are similar to those found with non-plant extracts and (4) finally
      mutations in conserved donor and acceptor sites abolished the production of the
      spliced product. Conclusions: This first report on the plant in vitro splicing
      assay opens new avenues to investigate plant spliceosome assembly and
      composition, and splicing regulatory mechanisms specific to plants.

PMID- 29321807
TI  - Different modulation of Panax notoginseng on the absorption profiling of
      triptolide and tripterine from Tripterygium wilfordii in rat intestine.
AB  - Background: Compatibility with Panax notoginseng (PN) reduced the plasma
      concentration of triptolide and delayed the Tmax of Tripterygium wilfordii (TW),
      the sovereign medicine of Qing-Luo Tong-Bi decoction, which hinted the absorption
      process of triptolide might be involved in decreasing the toxicity in liver and
      kidney. Methods: The absorption of triptolide, triptonide, wilforlide and
      tripterine from monomer, TW, TW-PN, TW-Caulis Sinomenii (TW-CS) and Qing-Luo Tong
      Bi were analyzed in duodenum, jejunum, ileum and colon of rat via single-pass
      intestinal perfusion model. An UPLC-MS/MS analysis method was developed to
      determine the concentration of triptolide, triptonide, wilforlide and tripterine
      in the inlet and outlet. Then Peff, 10 cm%ABS and Ka were calculated based on the
      perfusate flux, perfusate volume and candidate chemicals concentration. Results:
      The absorption of triptolide, triptonide, wilforlide and tripterine in duodenum,
      jejunum, ileum and colon was independent of concentration within range of 3-9
      MUg/mL. The target compounds, triptolide, triptonide, wilforlide and tripterine
      from the TW extract, showed higher absorption extent and rate than those
      administrated alone, and compared with the absorption situation of the chemicals
      of TW extract, the absorption of triptolide, triptonide and wilforlide of the
      extract of TW-PN, TW-CS and Qing-Luo Tong-Bi were decreased in these intestinal
      segments. However, PN-promoted tripterine absorption was observed in the
      intestine. Conclusions: Modulation of absorption of chemicals in TW by subsidiary
      herbs may be responsible for reinforcing the actions and neutralizing the adverse
      effects through compatibility in the formula of Qing-Luo Tong-Bi. PN inhibits the
      absorption of triptolide of TW and promote the absorption of tripterine.

PMID- 29321809
TI  - Quality of life, delinquency and psychosocial functioning of adolescents in
      secure residential care: testing two assumptions of the Good Lives Model.
AB  - Background: In this study, two assumptions derived from the Good Lives Model were
      examined: whether subjective Quality of Life is related to delinquent behaviour
      and psychosocial problems, and whether adolescents with adequate coping skills
      are less likely to commit delinquent behaviour or show psychosocial problems.
      Method: To this end, data of 95 adolescents with severe psychiatric problems who
      participated in a four-wave longitudinal study were examined. Subjective Quality
      of Life was assessed with the ten domains of the Lancashire Quality of Life
      Profile and coping skills with the Utrecht Coping List for Adolescents. Results:
      Results showed that adolescents who reported a lower Quality of Life on the
      health domain had more psychosocial problems at follow-up. No relationship was
      found between Quality of Life and delinquent behaviour. In addition, active and
      passive coping were associated with delinquent behaviour and psychosocial
      functioning at follow-up. Conclusions: Based on the results of this longitudinal
      study, the strongest support was found for the second assumption derived from the
      Good Lives Model. Adolescents with adequate coping skills are less likely to
      commit delinquent behaviour and have fewer psychosocial problems at follow-up.
      The current study provides support for the use of strength-based elements in the
      treatment programmes for adolescents in secure residential care.

PMID- 29321808
TI  - iTRAQ-based proteomic analysis to identify the molecular mechanism of Zhibai
      Dihuang Granule in the Yin-deficiency-heat syndrome rats.
AB  - Background: Zhibai Dihuang Granule (ZDG) is a traditional Chinese medicine which
      has been used to treat Yin-deficiency-heat (YDH) syndrome for thousands of years
      in China. However, little work has been conducted to explore the molecular
      mechanism of ZDG in YDH syndrome, and the processes of YDH syndrome prevention
      and treatment have been developed slowly. The present study was aimed to explore
      the therapeutic mechanism of ZDG on YDH syndrome. Methods: The YDH syndrome rats
      were induced by hot Chinese herbs, then treated by ZDG orally for 1 week. Body
      weight was measured every 2 days. After sacrifice, blood samples were collected
      and the thymus, adrenal glands, spleen, and liver were immediately removed and
      weighed. iTRAQ-based proteomics approach was applied to explore the serum protein
      alterations with the treatment of ZDG, and to investigate the underlying
      mechanism of ZDG in treating YDH syndrome. Results: The body weights of YDH
      syndrome rats were significantly decreased compared with control group, and
      increased in ZDG treated rats. The relative weights of thymus in YDH syndrome
      rats were increased compared with the control rats, and significantly decreased
      in after ZDG treatment. In the proteomic analyses, seventy-one proteins were
      differentially expressed in the YDH syndrome group and the ZDG treated group,
      including 10 up-regulated and 61 down-regulated proteins. Gene ontology analysis
      revealed that the differentially expressed proteins were mostly related to immune
      response, and pathway enrichment analysis showed that these proteins were
      enriched in coagulation and complement cascades. Enzyme-linked immunosorbent
      assay was performed to detect the protein levels in coagulation and complement
      cascades, and the results showed that complement component 5 levels were
      significantly increased, while fibrinogen gamma chain levels were significantly
      decreased in the ZDG treated group. Conclusions: We found that ZDG treatment
      could lead to proteins alteration in immune response, especially in coagulation
      and complement cascades. ZDG can up-regulate the proteins in the complement
      cascade to eliminate pathogens, and down-regulate the proteins in the coagulation
      cascade to suppress inflammation. Our study provides experimental basis to
      understand the therapeutic mechanism of ZDG and revealed that ZDG can regulate
      coagulation and complement cascades in treating YDH syndrome.

PMID- 29321810
TI  - Metabolic engineering of Pichia pastoris for production of isobutanol and
      isobutyl acetate.
AB  - Background: Interests in renewable fuels have exploded in recent years as the
      serious effects of global climate change become apparent. Microbial production of
      high-energy fuels by economically efficient bioprocesses has emerged as an
      attractive alternative to the traditional production of transportation fuels.
      Here, we engineered Pichia pastoris, an industrial workhorse in heterologous
      enzyme production, to produce the biofuel isobutanol from two renewable carbon
      sources, glucose and glycerol. Our strategy exploited the yeast's amino acid
      biosynthetic pathway and diverted the amino acid intermediates to the 2-keto acid
      degradation pathway for higher alcohol production. To further demonstrate the
      versatility of our yeast platform, we incorporated a broad-substrate-range
      alcohol-O-acyltransferase to generate a variety of volatile esters, including
      isobutyl acetate ester and isopentyl acetate ester. Results: The engineered
      strain overexpressing the keto-acid degradation pathway was able to produce 284
      mg/L of isobutanol when supplemented with 2-ketoisovalerate. To improve the
      production of isobutanol and eliminate the need to supplement the production
      media with the expensive 2-ketoisovalerate intermediate, we overexpressed a
      portion of the amino acid l-valine biosynthetic pathway in the engineered strain.
      While heterologous expression of the pathway genes from the yeast Saccharomyces
      cerevisiae did not lead to improvement in isobutanol production in the engineered
      P. pastoris, overexpression of the endogenous l-valine biosynthetic pathway genes
      led to a strain that is able to produce 0.89 g/L of isobutanol. Fine-tuning the
      expression of bottleneck enzymes by employing an episomal plasmid-based
      expression system further improved the production titer of isobutanol to 2.22
      g/L, a 43-fold improvement from the levels observed in the original strain.
      Finally, heterologous expression of a broad-substrate-range alcohol-O
      acyltransferase led to the production of isobutyl acetate ester and isopentyl
      acetate ester at 51 and 24 mg/L, respectively. Conclusions: In this study, we
      engineered high-level production of the biofuel isobutanol and the corresponding
      acetate ester by P. pastoris from readily available carbon sources. We envision
      that our work will provide an economic route to this important class of compounds
      and establish P. pastoris as a versatile production platform for fuels and
      chemicals.

PMID- 29321812
TI  - Construction of an ultrahigh-density genetic linkage map for Jatropha curcas L.
      and identification of QTL for fruit yield.
AB  - Background: As an important biofuel plant, the demand for higher yield Jatropha
      curcas L. is rapidly increasing. However, genetic analysis of Jatropha and
      molecular breeding for higher yield have been hampered by the limited number of
      molecular markers available. Results: An ultrahigh-density linkage map for a
      Jatropha mapping population of 153 individuals was constructed and covered
      1380.58 cM of the Jatropha genome, with average marker density of 0.403 cM. The
      genetic linkage map consisted of 3422 SNP and indel markers, which clustered into
      11 linkage groups. With this map, 13 repeatable QTLs (reQTLs) for fruit yield
      traits were identified. Ten reQTLs, qNF-1, qNF-2a, qNF-2b, qNF-2c, qNF-3, qNF-4,
      qNF-6, qNF-7a, qNF-7b and qNF-8, that control the number of fruits (NF) mapped to
      LGs 1, 2, 3, 4, 6, 7 and 8, whereas three reQTLs, qTWF-1, qTWF-2 and qTWF-3, that
      control the total weight of fruits (TWF) mapped to LGs 1, 2 and 3, respectively.
      It is interesting that there are two candidate critical genes, which may regulate
      Jatropha fruit yield. We also identified three pleiotropic reQTL pairs associated
      with both the NF and TWF traits. Conclusion: This study is the first to report an
      ultrahigh-density Jatropha genetic linkage map construction, and the markers used
      in this study showed great potential for QTL mapping. Thirteen fruit-yield reQTLs
      and two important candidate genes were identified based on this linkage map. This
      genetic linkage map will be a useful tool for the localization of other
      economically important QTLs and candidate genes for Jatropha.

PMID- 29321811
TI  - Gene stacking of multiple traits for high yield of fermentable sugars in plant
      biomass.
AB  - Background: Second-generation biofuels produced from biomass can help to decrease
      dependency on fossil fuels, bringing about many economic and environmental
      benefits. To make biomass more suitable for biorefinery use, we need a better
      understanding of plant cell wall biosynthesis. Increasing the ratio of C6 to C5
      sugars in the cell wall and decreasing the lignin content are two important
      targets in engineering of plants that are more suitable for downstream processing
      for second-generation biofuel production. Results: We have studied the basic
      mechanisms of cell wall biosynthesis and identified genes involved in
      biosynthesis of pectic galactan, including the GALS1 galactan synthase and the
      UDP-galactose/UDP-rhamnose transporter URGT1. We have engineered plants with a
      more suitable biomass composition by applying these findings, in conjunction with
      synthetic biology and gene stacking tools. Plants were engineered to have up to
      fourfold more pectic galactan in stems by overexpressing GALS1, URGT1, and UGE2,
      a UDP-glucose epimerase. Furthermore, the increased galactan trait was engineered
      into plants that were already engineered to have low xylan content by restricting
      xylan biosynthesis to vessels where this polysaccharide is essential. Finally,
      the high galactan and low xylan traits were stacked with the low lignin trait
      obtained by expressing the QsuB gene encoding dehydroshikimate dehydratase in
      lignifying cells. Conclusion: The results show that approaches to increasing C6
      sugar content, decreasing xylan, and reducing lignin content can be combined in
      an additive manner. Thus, the engineered lines obtained by this trait-stacking
      approach have substantially improved properties from the perspective of biofuel
      production, and they do not show any obvious negative growth effects. The
      approach used in this study can be readily transferred to bioenergy crop plants.

PMID- 29321813
TI  - Novel concept of a modular hip implant could contribute to less implant failure
      in THA: a hypothesis.
AB  - Background: The modularity in total hip arthroplasty (THA) allows orthopaedic
      surgeons for an exact reconstruction of hip biomechanical parameters especially
      in revision and tumor arthroplasty. Modular structured femoral stems using taper
      junctions showed increased implant breakage in the recent past. Presentation of
      the hypothesis: We hypothesize that a novel modular stem-neck-interface leads to
      less implant breakage compared to conventional femoral stems. Testing of the
      hypothesis: For this purpose, a novel modular femoral stem for THA was to design
      and manufacture. Therefore, three different variants of interface mechanisms were
      developed that enable a simple connection between the stem and the neck modules
      and allow for intra-operatively adjustment. Three prototypes A, B and C were
      manufactured and subsequently dynamic fatigue (ISO 7206-6) and body donor tested.
      Implication of the hypothesis: Modularity in THA is mainly applied in THA as well
      as in revision and tumor arthroplasty. Modular implants are barely used because
      of the high risk of breakage. Another risks in this context are taper fretting,
      corrosion and disconnection. With the novel design, it should be possible to
      detach the stem and neck module intra-operatively to adapt the anatomical
      situation. The novel coupling mechanism of the rotating interface seems to be the
      most suitable for a secure stem-neck connection and is characterized by good
      intraoperative handling.

PMID- 29321814
TI  - The epigenetic clock and objectively measured sedentary and walking behavior in
      older adults: the Lothian Birth Cohort 1936.
AB  - Background: Estimates of biological age derived from DNA-methylation patterns
      known as the epigenetic clock-are associated with mortality, physical and
      cognitive function, and frailty, but little is known about their relationship
      with sedentary behavior or physical activity. We investigated the cross-sectional
      relationship between two such estimates of biological age and objectively
      measured sedentary and walking behavior in older people. Methods: Participants
      were 248 members of the Lothian Birth Cohort 1936. At age 79 years, sedentary
      behavior and physical activity were measured over 7 days using an activPAL
      activity monitor. Biological age was estimated using two measures of DNA
      methylation-based age acceleration-i.e., extrinsic and intrinsic epigenetic age
      acceleration. We used linear regression to assess the relationship between these
      two estimates of biological age and average daily time spent sedentary, number of
      sit-to-stand transitions, and step count. Results: Of the six associations
      examined, only two were statistically significant in initial models adjusted for
      age and sex alone. Greater extrinsic age acceleration was associated with taking
      fewer steps (regression coefficient (95% CI) - 0.100 (- 0.008, - 0.001), and
      greater intrinsic age acceleration was associated with making more sit-to-stand
      transitions (regression coefficient (95% CI) 0.006 (0.0001, 0.012). When we
      controlled for multiple statistical testing, neither of these associations
      survived correction (both P >= 0.17). Conclusion: In this cross-sectional study
      of 79-year-olds, we found no convincing evidence that biological age, as indexed
      by extrinsic or intrinsic epigenetic age acceleration, was associated with
      objectively measured sedentary or walking behavior.

PMID- 29321815
TI  - Circulating plasma microRNA profiling in patients with
      polymyositis/dermatomyositis before and after treatment: miRNA may be associated
      with polymyositis/dermatomyositis.
AB  - Background: MicroRNAs (miRNAs) are involved in the regulation of key biological
      processes and have been implicated in various diseases, including autoimmune
      disorders. The pathogenesis of polymyositis (PM) and dermatomyositis (DM) is
      considered to be mediated by autoimmune reactions. To determine miRNA role in the
      development and progression of PM and DM, we performed plasma miRNA profiling in
      PM/DM patients before and after treatment. Methods: Total RNA was isolated from
      plasma of 10 patients before and after treatment with prednisolone, or, in case
      of prednisolone resistance or complications, with the combination of calcineurin
      inhibitors (cyclosporine or tacrolims) and/or pulse intravenous cyclophosphamide.
      The expression of miRNAs was determined using miRNA microarray and validated by
      qRT-PCR. Results: More differentially expressed miRNAs were found in plasma of DM
      patients compared to PM patients before and after treatment, and their profiles
      were different. Among the differentially expressed plasma miRNA identified by
      microarray, the levels of hsa-miR-4442 were confirmed by qRT-PCR to be
      significantly decreased by treatment. In addition, plasma hsa-miR-4442 content in
      active PM/DM significantly exceeded that in other active autoimmune diseases such
      as rheumatoid arthritis and systemic lupus erythematosus, as well as in healthy
      individuals. The level of plasma hsa-miR-4442 was positively correlated with
      Skeletal Disease Activity in MITAX (Myositis Intention to Treat Activity Index).
      Conclusion: This is the first report describing plasma miRNA expression profiles
      in PM/DM patients. The present data suggest that plasma levels of miRNAs may be
      associated with polymyositis/dermatomyositis and hsa-miR-4442 could be used as a
      biomarker for PM/DM diagnosis and/or disease activity.

PMID- 29321816
TI  - ERBB signaling in CTCs of ovarian cancer and glioblastoma.
AB  - Circulating Tumor Cells (CTCs) are floating cell populations, which are resistant
      to anoikis after detachment from the primary sites and travel through the
      circulatory and lymphatic systems to disseminate throughout the body. CTCs are
      considered as seed cells for metastasis, and thus isolation of CTCs does not
      require any invasive procedure. Based on the nature and location of ovarian
      cancer and glioblastoma, the role of CTCs and hematogenous (carried by blood)
      spreading of tumor cells in these cancers were not understood well. Dysregulation
      of epidermal growth factor receptor (EGFR/ERBB) family members due to their
      overexpression and/or mutation have been known to contribute to the etiology and
      progression of ovarian cancer and glioblastoma. However, the role of ERBB
      receptors on CTC formation of ovarian cancer and glioblastoma is not well
      established. This report highlights the role of ERBB family receptors on
      resistance to anoikis and CTC formation in ovarian cancer and glioblastoma.
      Recent research on CTCs demonstrates that capturing ERBB receptor positive cells
      from circulating system is an efficient approach to isolate CTCs for genomic and
      proteomic characterization of tumor cells. Therefore, ERBB-targeted isolation of
      CTCs would help to design therapy to treat cancer, determine drug responses and
      drug-resistant mechanisms in cancer patients.

PMID- 29321817
TI  - Enhanced MYC association with the NuA4 histone acetyltransferase complex mediated
      by the adenovirus E1A N-terminal domain activates a subset of MYC target genes
      highly expressed in cancer cells.
AB  - The proto-oncogene MYC is a transcription factor over-expressed in many cancers
      and required for cell survival. Its function is regulated by histone
      acetyltransferase (HAT) complexes, such as the GCN5 complex and the NuA4/Tip60
      complex. However, the roles of the HAT complexes during MYC function in cancer
      have not been well characterized. We recently showed that adenovirus E1A and its
      N-terminal 80 aa region, E1A 1-80, interact with the NuA4 complex, through the
      E1A TRRAP-targeting (ET) domain, and enhance MYC association with the NuA4
      complex. We show here that the ET domain mainly targets the MYC-NuA4 complex. By
      global gene expression analysis using E1A 1-80 and deletion mutants, we have
      identified a panel of genes activated by targeting the MYC-NuA4 complex and
      notably enriched for genes involved in ribosome biogenesis and gene expression. A
      second panel of genes is activated by E1A 1-80 targeting of both the MYC-NuA4
      complex and p300, and is enriched for genes involved in DNA replication and cell
      cycle processes. Both panels of genes are highly expressed in cancer cells. Since
      the ET domain is essential for E1A-mediated cellular transformation, our results
      suggest that MYC and the NuA4 complex function cooperatively in cell
      transformation and cancer.

PMID- 29321818
TI  - EWS-FLI-1 creates a cell surface microenvironment conducive to IGF signaling by
      inducing pappalysin-1.
AB  - Ewing sarcoma is an aggressive cancer of bone and soft tissue in children with
      poor prognosis. It is characterized by the chromosomal translocation between EWS
      and an Ets family transcription factor, most commonly FLI-1. EWS-FLI-1 fusion
      accounts for 85% of Ewing sarcoma cases. EWS-FLI-1 regulates the expression of a
      number of genes important for sarcomagenesis, can transform NIH3T3 and C3H10T1/2
      cells, and is necessary for proliferation and tumorigenicity of Ewing sarcoma
      cells, suggesting that EWS-FLI-1 is the causative oncoprotein. Here we report
      that EWS-FLI-1 induces the expression of pappalysin-1 (PAPPA), a cell surface
      protease that degrades IGF binding proteins (IGFBPs) and increases the
      bioavailability of IGF. EWS-FLI-1 binds to the pappalysin-1 gene promoter and
      stimulates the expression of pappalysin-1, leading to degradation of IGFBPs and
      enhanced IGF signaling. Silencing of pappalysin-1 strongly inhibited anchorage
      dependent and anchorage-independent growth as well as xenograft tumorigenicity of
      Ewing sarcoma cells. These results suggest that EWS-FLI-1 creates a cell surface
      microenvironment conducive to IGF signaling by inducing pappalysin-1, which
      emerged as a novel target to inhibit IGF signaling in Ewing sarcoma.

PMID- 29321819
TI  - The induction of endoreduplication and polyploidy by elevated expression of 14-3
      3gamma.
AB  - Several studies have demonstrated that specific 14-3-3 isoforms are frequently
      elevated in cancer and that these proteins play a role in human tumorigenesis. 14
      3-3gamma, an isoform recently demonstrated to function as an oncoprotein, is
      overexpressed in a variety of human cancers; however, its role in promoting
      tumorigenesis remains unclear. We previously reported that overexpression of 14-3
      3gamma caused the appearance of polyploid cells, a phenotype demonstrated to have
      profound tumor promoting properties. Here we examined the mechanism driving 14-3
      3gamma-induced polyploidization and the effect this has on genomic stability.
      Using FUCCI probes we showed that these polyploid cells appeared when diploid
      cells failed to enter mitosis and subsequently underwent endoreduplication. We
      then demonstrated that 14-3-3gamma-induced polyploid cells experience significant
      chromosomal segregation errors during mitosis and observed that some of these
      cells stably propagate as tetraploids when isolated cells were expanded into
      stable cultures. These data lead us to conclude that overexpression of the 14-3
      3gamma promotes endoreduplication. We further investigated the role of 14-3
      3gamma in human NSCLC samples and found that its expression is significantly
      elevated in polyploid tumors. Collectively, these results suggests that 14-3
      3gamma may promote tumorigenesis through the production of a genetically unstable
      polyploid intermediate.

PMID- 29321820
TI  - Dysregulation of AKT3 along with a small panel of mRNAs stratifies high-grade
      serous ovarian cancer from both normal epithelia and benign tumor tissues.
AB  - Screening methods of High-Grade Serous Ovarian Cancer (HGSOC) lack specificity
      and sensitivity, partly due to benign tumors producing false-positive findings.
      We utilized a differential expression analysis pipeline on malignant tumor (MT)
      and normal epithelial (NE) samples, and also filtered the results to discriminate
      between MT and benign tumor (BT). We report that a panel of 26 dysregulated genes
      stratifies MT from both BT and NE. We further validated our findings by utilizing
      unsupervised clustering methods on two independent datasets. We show that the 26
      genes panel completely distinguishes HGSOC from NE, and produces a more accurate
      classification between HGSOC and BT. Pathway analysis reveals that AKT3 is of
      particular significance, because of its high fold change and appearance in the
      majority of the dysregulated pathways. mRNA patterns of AKT3 suggest essential
      connections with tumor growth and metastasis, as well as a strong biomarker
      potential when used with 3 other genes (PTTG1, MND1, CENPF). Our results show
      that dysregulation of the 26-mRNA signature panel provides an evidence of
      malignancy and contribute to the design of a high specificity biomarker panel for
      detection of HGSOC, potentially in an early more curable stage.

PMID- 29321821
TI  - The influence of glyoxalase 1 gene polymorphism on its expression at different
      stages of breast cancer in Egyptian women.
AB  - Aim: To assess the association of GLO1 C332C gene polymorphism with breast cancer
      risk at different stages of the disease and to investigate the effect of this
      gene polymorphism on its mRNA expression and enzyme activity. Methods: GLO1 C332C
      gene polymorphism was analyzed by PCR-RFLP in 100 healthy controls and 200
      patients with breast cancer (100 patients with stage I & II and 100 patients with
      stage III & IV). GLO1 mRNA expression was measured by real time PCR. Serum GLO1
      enzyme activity was measured colorimetrically. Results: GLO1 A allele was
      associated with increased risk of breast cancer [OR (95%CI)= 2.8(1.9-4.1), P <
      0.001]. Its frequency was significantly higher among advanced stages of breast
      cancer compared with localized tumors (OR (95%CI)= 1.9(1.3-2.9), p < 0.001). GLO1
      mRNA expression and enzyme activity were significantly higher in breast cancer
      patients compared to controls and they were much higher in the advanced stages of
      the disease (P < 0.001). Carriers of AA genotype showed higher GLO1 expression
      and enzyme activity compared with carriers of CC genotype. Conclusion: GLO1 C332C
      SNP was associated with overexpression of GLO1 mRNA and higher enzyme activity in
      breast cancer patients suggesting its role in the development of breast cancer
      and its progression from localized to advanced.

PMID- 29321823
TI  - Yin and Yang of mesenchymal stem cells and aplastic anemia.
AB  - Acquired aplastic anemia (AA) is a bone marrow failure syndrome characterized by
      peripheral cytopenias and bone marrow hypoplasia. It is ultimately fatal without
      treatment, most commonly from infection or hemorrhage. Current treatments focus
      on suppressing immune-mediated destruction of bone marrow stem cells or replacing
      hematopoietic stem cells (HSCs) by transplantation. Our incomplete understanding
      of the pathogenesis of AA has limited development of targeted treatment options.
      Mesenchymal stem cells (MSCs) play a vital role in HSC proliferation; they also
      modulate immune responses and maintain an environment supportive of
      hematopoiesis. Some of the observed clinical manifestations of AA can be
      explained by mesenchymal dysfunction. MSC infusions have been shown to be safe
      and may offer new approaches for the treatment of this disorder. Indeed,
      infusions of MSCs may help suppress auto-reactive, T-cell mediated HSC
      destruction and help restore an environment that supports hematopoiesis. Small
      pilot studies using MSCs as monotherapy or as adjuncts to HSC transplantation
      have been attempted as treatments for AA. Here we review the current
      understanding of the pathogenesis of AA and the function of MSCs, and suggest
      that MSCs should be a target for further research and clinical trials in this
      disorder.

PMID- 29321822
TI  - Pursuing meaningful end-points for stem cell therapy assessment in ischemic
      cardiac disease.
AB  - Despite optimal interventional and medical therapy, ischemic heart disease is
      still an important cause of morbidity and mortality worldwide. Although not
      included in standard of care rehabilitation, stem cell therapy (SCT) could be a
      solution for prompting cardiac regeneration. Multiple studies have been published
      from the beginning of SCT until now, but overall no unanimous conclusion could be
      drawn in part due to the lack of appropriate end-points. In order to appreciate
      the impact of SCT, multiple markers from different categories should be
      considered: Structural, biological, functional, physiological, but also major
      adverse cardiac events or quality of life. Imaging end-points are among the most
      used - especially left ventricle ejection fraction (LVEF) measured through
      different methods. Other imaging parameters are infarct size, myocardial
      viability and perfusion. The impact of SCT on all of the aforementioned end
      points is controversial and debatable. 2D-echocardiography is widely exploited,
      but new approaches such as tissue Doppler, strain/strain rate or 3D
      echocardiography are more accurate, especially since the latter one is comparable
      with the MRI gold standard estimation of LVEF. Apart from the objective
      parameters, there are also patient-centered evaluations to reveal the benefits of
      SCT, such as quality of life and performance status, the most valuable from the
      patient point of view. Emerging parameters investigating molecular pathways such
      as non-coding RNAs or inflammation cytokines have a high potential as prognostic
      factors. Due to the disadvantages of current techniques, new imaging methods with
      labelled cells tracked along their lifetime seem promising, but until now only
      pre-clinical trials have been conducted in humans. Overall, SCT is characterized
      by high heterogeneity not only in preparation, administration and type of cells,
      but also in quantification of therapy effects.

PMID- 29321824
TI  - High frequency of CD34+CD38-/low immature leukemia cells is correlated with
      unfavorable prognosis in acute myeloid leukemia.
AB  - AIM: To evaluate the importance of the CD34+CD38- cell population when compared
      to the CD34+CD38+/low and CD34+CD38+/high leukemic cell sub-populations and to
      determine its correlations with leukemia characteristics and known prognostic
      factors, as well as with response to therapy and survival. METHODS: Two hundred
      bone marrow samples were obtained at diagnosis from 200 consecutive patients with
      newly diagnosed acute myeloid leukemia (AML) were studied between September 2008
      and December 2010 at our Institution (Hematology Department, Lyon, France). The
      CD34/CD38 cell profile was analyzed by multiparameter flowcytometry approach
      using 8C panels and FACS CANTO and Diva software (BD Bioscience). RESULTS: We
      analyzed CD34 and CD38 expression in bone marrow samples of 200 AML patients at
      diagnosis, and investigated the prognostic value of the most immature CD34+CD38-
      population. Using a cut-off value of 1% of CD34+CD38- from total "bulk leukemic
      cells" we found that a high (> 1%) level of CD34+CD38- blasts at diagnosis was
      correlated with advanced age, adverse cytogenetics as well as with a lower rate
      of complete response after induction and shorter disease-free survival. In a
      multivariate analysis considering age, leukocytosis, the % of CD34+ blasts cells
      and the standardized cytogenetic and molecular risk subgroups, a percentage of
      CD34+CD38- leukemic cells > 1% was an independent predictor of DFS [HR = 2.8
      (1.02-7.73), P = 0.04] and OS [HR = 2.65 (1.09-6.43), P = 0.03]. CONCLUSION:
      Taken together, these results show that a CD34/CD38 "backbone" for leukemic cell
      analysis by multicolour flowcytometry at diagnosis provides useful prognostic
      information.

PMID- 29321825
TI  - Umbilical cord blood stem cell treatment for a patient with psoriatic arthritis.
AB  - Clinical and laboratory results document psoriatic arthritis in a 56-year old
      patient. The symptoms did not resolve with standard treatments (nonsteroidal anti
      inflammatory drugs, steroids and methotrexate). TNF-alpha inhibitors
      (certolizumab pegol and adalimumab) were added to the treatment regime, with some
      adverse effects. A trial of human umbilical cord stem cell therapy was then
      initiated. The stem cells were enriched and concentrated from whole cord blood,
      by removal of erythrocytes and centrifugation. The patient received several
      infusions of cord blood stem cells, through intravenous and intra-articular
      injections. These stem cell treatments correlated with remission of symptoms
      (joint pain and psoriatic plaques) and normalized serologic results for the
      inflammatory markers C-reactive protein and erythrocyte sedimentation rate. These
      improvements were noted within the first thirty days post-treatment, and were
      sustained for more than one year. The results of this trial suggest that cord
      blood stem cells may have important therapeutic value for patients with psoriatic
      arthritis, particularly for those who cannot tolerate standard treatments.

PMID- 29321826
TI  - The role of automatic defensive responses in the development of posttraumatic
      stress symptoms in police recruits: protocol of a prospective study.
AB  - Background: Control over automatic tendencies is often compromised in challenging
      situations when people fall back on automatic defensive reactions, such as freeze
      fight-flight responses. Stress-induced lack of control over automatic defensive
      responses constitutes a problem endemic to high-risk professions, such as the
      police. Difficulties controlling automatic defensive responses may not only
      impair split-second decisions under threat, but also increase the risk for and
      persistence of posttraumatic stress disorder (PTSD) symptoms. However, the
      significance of these automatic defensive responses in the development and
      maintenance of trauma-related symptoms remains unclear due to a shortage of large
      scale prospective studies. Objective: The 'Police-in-Action' study is conducted
      to investigate the role of automatic defensive responses in the development and
      maintenance of PTSD symptomatology after trauma exposure. Methods: In this
      prospective study, 340 police recruits from the Dutch Police Academy are tested
      before (wave 1; pre-exposure) and after (wave 2; post-exposure) their first
      emergency aid experiences as police officers. The two waves of data assessment
      are separated by approximately 15 months. To control for unspecific time effects,
      a well-matched control group of civilians (n = 85) is also tested twice,
      approximately 15 months apart, but without being frequently exposed to
      potentially traumatic events. Main outcomes are associations between (changes in)
      behavioural, psychophysiological, endocrine and neural markers of automatic
      defensive responses and development of trauma-related symptoms after trauma
      exposure in police recruits. Discussion: This prospective study in a large group
      of primary responders enables us to distinguish predisposing from acquired
      neurobiological abnormalities in automatic defensive responses, associated with
      the development of trauma-related symptoms. Identifying neurobiological
      correlates of (vulnerability for) trauma-related psychopathology may greatly
      improve screening for individuals at risk for developing PTSD symptomatology and
      offer valuable targets for (early preventive) interventions for PTSD.

PMID- 29321827
TI  - High seroprevalence of Rift Valley fever phlebovirus in domestic ruminants and
      African Buffaloes in Mozambique shows need for intensified surveillance.
AB  - Introduction: Rift Valley fever (RVF) is an arthropod-borne disease that affects
      both animals and humans. RVF phlebovirus (RVFPV) is widespread in Africa and
      Arabian Peninsula. In Mozambique, outbreaks were reported in South;
      seroprevalence studies performed in livestock and water buffaloes were limited to
      central and south regions. We evaluated the seroprevalence of RVFPV among
      domestic ruminants and African buffaloes from 7 of 10 provinces of Mozambique, to
      understand the distribution of RVFPV and provide data for further RVF control
      programs. Materials and methods: A total of 1581 blood samples were collected in
      cattle, 1117 in goats, 85 in sheep and 69 in African buffaloes, between 2013 and
      2014, and the obtained sera were analyzed by ELISA. Results and discussion: The
      overall seroprevalence of RVFPV domestic ruminants and African buffaloes was
      25.6%. The highest was observed in cattle (37.3%) and African buffaloes (30.4%),
      which were higher than in previous studies within Mozambique. In south and
      central regions, the overall seroprevalences were higher (14.9%-62.4%) than in
      the north. Conclusion: This study showed the presence of anti-RVFPV antibodies in
      animals from all sampled provinces, suggesting that RVFPV is actively circulating
      among domestic ruminants and African buffaloes in Mozambique, therefore
      surveillance should be intensified.

PMID- 29321828
TI  - Exendin-4 protects mice from D-galactose-induced hepatic and pancreatic
      dysfunction.
AB  - Investigations into pharmaceutical intervention of pancreatic and hepatic
      dysfunction associated with metabolic disturbances have received relatively
      little attention. The aim of this study was to investigate the protective effects
      of exendin-4 in mice receiving D-galactose, a reducing sugar that triggers ROS
      production and inflammatory mediators affecting the pancreas and liver. Exendin-4
      is an United States Food and Drug Administration (FDA) approved glucagon-like
      peptide that increases insulin dependent glycogen synthesis and glucose uptake.
      Male NMRI mice (20-25 g), 3 months of age, were randomly divided into 6 groups of
      12 mice each: control, exendin-4 (1 nmol/kg), exendin-4 (10 nmol/kg), D
      galactose, D-galactose + exendin-4 (1 nmol/kg) and D-galactose + exendin-4 (10
      nmol/kg). D-galactose (500 mg/kg) was given daily by oral gavage for 6 weeks.
      During the last 10 days, exendin-4 (1 and 10 nmol/kg) was injected
      intraperitoneally daily. Glucose, insulin, insulin resistance, lipid profiles,
      and hepatic enzyme levels significantly increased in the D-galactose group (p <
      0.05), along with a significant decrease in superoxide dismutase activity and
      pancreatic islet insulin secretion (p < 0.05). Exendin-4 decreased D-galactose
      induced increases in serum glucose and insulin, insulin resistance, lipid
      profiles, and hepatic enzymes, and improved pancreatic islet insulin secretion
      and antioxidant defense status. The results show that exendin-4 can prevent
      complications in mice with compromised pancreatic and hepatic function. Long term
      administration of D-galactose in mice may be a useful model to study insulin
      resistance, metabolic syndrome, and aging.

PMID- 29321829
TI  - DNA Methylation in Stroke. Update of Latest Advances.
AB  - Epigenetic modifications are hereditable and modifiable factors that do not alter
      the DNA sequence. These epigenetic factors include DNA methylation, acetylation
      of histones and non-coding RNAs. Epigenetic factors have mainly been associated
      with cancer but also with other diseases and conditions such as diabetes or
      obesity. In addition, epigenetic modifications could play an important role in
      cardiovascular diseases, including stroke. We review the latest advances in
      stroke epigenetics, focusing on DNA methylation studies and the future
      perspectives in this field.

PMID- 29321830
TI  - Cost-effectiveness of evolocumab in treatment of heterozygous familial
      hypercholesterolaemia in Bulgaria: measuring health benefit by effectively
      treated patient-years.
AB  - Background: An elevated level of low-density lipoprotein cholesterol (LDL-C)
      constitutes one of the most important modifiable risk factors for cardiovascular
      disease (CVD). Individuals with heterozygous familial hypercholesterolaemia
      (HeFH) are particularly vulnerable to CVD events. The addition of evolocumab to
      statins has shown marked reductions in LDL-C levels. The objective of this
      analysis is to demonstrate the clinical and economic value of LDL-C lowering with
      evolocumab from the Bulgarian public health care perspective. Methods: A disease
      specific measure of health benefit was devised: Effectively treated patient-years
      (ETPYs) combine length of life with the likelihood of attaining best-practice
      recommendations on LDL-C lowering. "Effective treatment" was defined as a
      reduction in LDL-C levels of >=50%. A Markov cohort state-transition model was
      adapted, considering a life-long treatment duration. Demographics, baseline
      characteristics and efficacy data were taken from the RUTHERFORD-2 trial. The
      model uses the relationship between LDL-C lowering and reduced CVD event rates
      observed in the meta-analyses conducted by the Cholesterol Treatment Trialists'
      Collaboration. Outcomes and costs (from year 2015) were discounted at an annual
      rate of 5%. Sensitivity analyses were conducted to assess uncertainty surrounding
      the results. Results: The total incremental costs of evolocumab added to statins
      versus statins alone are BGN 120,329 while adding 9.30 ETPYs over lifetime. These
      results imply an incremental cost per ETPY of BGN 12,937 (US$ 7,215; ? 6,604).
      The use of evolocumab is associated with a relative reduction in the CVD event
      rate by 38% (18% per 1 mmol/L). Conclusions: Adding evolocumab to statins may be
      considered cost-effective in light of an additional expense per patient-year
      gained in which individuals with HeFH receive effective treatment under the terms
      of international prevention guidelines. ETPYs are an intuitive and clinically
      meaningful measure of patient benefit that, in relation to costs, can support
      health care decision-making that considers quality of care.

PMID- 29321831
TI  - Changes in smoking prevalence and cessation support, and factors associated with
      successful smoking cessation in Swedish patients with asthma and COPD.
AB  - Introduction: Our aim was to investigate changes in smoking prevalence, smoking
      cessation support and factors associated with successful smoking cessation in
      patients with asthma and COPD. Methods: Questionnaires about available smoking
      cessation resources were completed by 54 primary health-care centers and 14
      hospitals in central Sweden in 2005 and 2012. Patient data were collected using
      record reviews and patients questionnaires for two cohorts of randomly selected
      asthma and COPD patients in 2005 (n = 2306; with a follow up in 2012), and in
      2014/2015 (n = 2620). Smoking prevalence, available individual and group smoking
      cessation support, and factors associated with successful smoking cessation were
      explored. Results: Smoking prevalence decreased from 11% to 6% (p < 0.0001) in
      patients with asthma but was almost unchanged in patients with COPD (28 to 26%, p
      = 0.37). Smoking cessation support increased from 53% to 74% (p = 0.01). A high
      cardiovascular risk factor level, including diabetes mellitus and hypertension
      was associated with improved smoking cessation in patients with asthma (OR (95%
      CI) 3.87 (1.04-14.4), p = 0.04). A higher magnitude success was observed in men
      with asthma (OR (95% CI) 27.9 (1.73-449), p = 0.02). More highly educated women
      with asthma had successful greater smoking cessation (4.76 (1.22-18.7), p =
      0.04). No significant associations were found in COPD. Conclusions: The smoking
      prevalence in patients with asthma but not in COPD has almost halved in Sweden
      during a 7-year period. The availability of smoking cessation support has
      increased. Suggested factors related to successful smoking cessation are higher
      level of education in women with asthma and cardiovascular risk factors in men
      and women with asthma.

PMID- 29321832
TI  - Access to Liver Transplantation and Patient Survival among Asian Populations: Pre
      Share 35 vs Post-Share 35.
AB  - Background: Studies addressing ethnic disparities and trends in liver
      transplantation for Asian population are scant. Objective: To examine the impact
      of Share 35 policy on Asian patients' access to liver transplantation and
      outcomes since its implementation in June 2013. Methods: A total of 11,910 adult
      white and Asian patients who were registered for deceased donor liver
      transplantation between 2012 and 2015, was identified from the United Network for
      Organ Sharing database. Logistic regression and proportional hazard models with
      adjustment for demographic, clinical and geographic factors were used to model
      the access to liver transplantation and patient survival. Stratification on pre-
      and post-Share 35 periods was performed to compare the first 18 months of Share
      35 policy to an equivalent period. Results: Comparison of the pre- and post-Share
      35 periods showed a significant decrease in time on waiting list and higher
      proportions of patients receiving liver transplantation for Asian patients.
      Asians shared similar transplant rates as whites (OR: 1.15, 95% CI: 0.80-1.67)
      but experienced significantly longer waiting time (HR: 0.56, 95% CI: 0.34-0.92)
      before they received liver transplantation after Share 35 policy took effect. No
      significant post-transplantation survival difference was observed between Asians
      and whites at the 18-month outcome. Conclusion: Although benefited from the Share
      35 policy, Asian patients are still at greater risk of disparities in access to
      liver transplantation.

PMID- 29321833
TI  - The Learning Curve of Pure Retroperitoneoscopic Donor Nephrectomy.
AB  - Background: Retroperitoneoscopic donor nephrectomy (RDN) is a well-established
      modality for the procurement of kidneys for renal transplantation. However the
      learning curve of pure RDN is not yet defined. Defining the learning curve will
      help in proper mentorship of the new donor surgeons besides providing safety to
      the donors. Objective: To define the learning curve of pure RDN. Methods: We
      analyzed the prospectively collected data of 102 voluntary kidney donors who
      underwent RDN by a single surgeon between August 2012 and April 2015 at our
      center. The donors were classified into group A (1-34), group B (35-68), and
      group C (69-102) according to the chronological order of their surgery. Left RDN
      was performed in 28 (82%), 25 (74%), and 28 (82%) donors of group A, B, and C,
      respectively. Right RDN was performed in 6 (18%), 9 (26%), and 6 (18%) donors of
      group A, B, and C, respectively. The clinical data were analyzed for each group.
      Results: Statistically significant difference was observed for the mean operative
      time (p<0.01) and warm ischemia time (p<0.04). The operative time remained around
      200 minutes after the initial 35 cases. Conclusion: The learning curve of pure
      RDN was 35 cases, although the mastery requires more number of cases to be
      performed.

PMID- 29321834
TI  - Increased c-myc and miR-33 Expression in Expanded Hematopoietic Stem Cells
      Cultured on Adipose Stem Cells Feeder Layer.
AB  - Background: Umbilical cord blood has been used for transplantation in
      regenerative medicine of hematological disorders. MicroRNAs are important
      regulators of gene expression that control both physiological and pathological
      processes such as development and cancer. Some studies have shown that miR-33,
      p53 and c-myc have critical roles in control of self-renewal cells. Objective: To
      understand the effect of adipose-derived mesenchymal stem cells (ADSCs), as a
      feeder layer, on expansion of HSCs, the expression of p53 and miR-33a were
      evaluated. Methods: Isolated human ADSCs in passage 3 were cultured as a feeder
      layer. Ex vivo cultures of cord blood CD34+ cells were performed in three culture
      conditions for 7 days: cytokines with ADSCs feeder layer, cytokines without ADSCs
      feeder layer, and co-culture with ADSCs without cytokine. Expression of genes
      p53, c-myc and miR-33 were analyzed by real-time PCR. Results: The expression of
      p53 was significantly down-regulated in HSCs directly cultured on ADSCs feeder
      layer compared to that cultured without feeder layer. The expression of miR-33a
      was significantly up-regulated in HSCs directly cultured on feeder layer compare
      to that cultured without feeder layer. Conclusion: Defining the role of ADSCs in
      controlling the HSC self-renewal through miR-33, p53 and c-myc may lead to the
      treatment and prevention of hematopoietic disorders.

PMID- 29321836
TI  - Acute Hepatic Allograft Rejection in Pediatric Recipients: Independent Factors.
AB  - Background: Acute cellular rejection (ACR) has a reversible effect on graft and
      its survival. Objective: To evaluate the relation between ACR and clinical
      factors in recipients of liver transplant allografts. Methods: 47 consecutive
      liver recipients were retrospectively studied. Their data were extracted from
      records and analyzed. Results: 38 (81%) of the 47 recipients experienced ACR
      during a 24-month follow-up. The rate of rejection was associated with none of
      the studied factors-recipient's blood group, sex, age, familial history of
      disease, drugs and blood products received, type of donor, and Child score and
      class. Conclusion: During a limited follow-up period, we did not find any
      association between ACR and suspected risk factors.

PMID- 29321835
TI  - Osteoblast Differentiation on Collagen Scaffold with Immobilized Alkaline
      Phosphatase.
AB  - Background: In tissue engineering, scaffold characteristics play an important
      role in the biological interactions between cells and the scaffold. Cell
      adhesion, proliferation, and activation depend on material properties used for
      the fabrication of scaffolds. Objective: In the present investigation, we used
      collagen with proper characteristics including mechanically stability,
      biodegradability and low antigenicity. Optimization of the scaffold was done by
      immobilization of alkaline phosphatase on the collagen surface via cross-linking
      method, because this enzyme is one of the most important markers of osteoblast,
      which increases inorganic phosphate concentration and promote mineralization of
      bone formation. Methods: Alkaline phosphatase was immobilized on a collagen
      surface by 1-ethyl-3-(dimethylaminopropyl) carbodiimide hydrochloride, as a
      reagent. Then, rat mesenchymal stem cells were cultured in osteogenic medium in
      control and treated groups. The osteogenesis-related genes were compared between
      treatments (differentiated cells with immobilized alkaline phosphatase/collagen
      scaffold) and control groups (differentiated cells on collagen surface without
      alkaline phosphatase) on days 3 and 7 by quantitative real-time PCR (QIAGEN
      software). Results: Several genes, including alkaline phosphatase, collagen type
      I and osteocalcine associated with calcium binding and mineralization, showed
      upregulation in expression during the first 3 days, whereas tumor necrosis factor
      alpha, acting as an inhibitor of differentiation, was down-regulated during
      osteogenesis. Conclusion: Collagen scaffold with immobilized alkaline phosphatase
      can be utilized as a good candidate for enhancing the differentiation of
      osteoblasts from mesenchymal stem cells.

PMID- 29321837
TI  - Acute Appendicitis after Liver Transplantation: A Case Report and Review of the
      Literature.
AB  - Acute appendicitis is one of the most common etiologies for acute abdomen.
      However, fewer than 30 cases of acute appendicitis after liver transplantation
      have so far been reported in the literature. Previous case studies have concluded
      that acute appendicitis after liver transplantation may present differently than
      in non-immunosuppressed patients and thus may lead to more complications. Herein,
      we describe the fourth case of laparoscopic appendectomy in a 40-year-old female
      presenting with an acute abdomen, 10 years after orthotopic liver transplantation
      for autoimmune hepatitis. Additionally, we review the literature, and emphasize
      the importance for laparoscopic, rather than open appendectomy after liver
      transplantation. Overall, despite the small number of reported cases of
      appendicitis after orthotopic liver transplantation, we found the incidence and
      clinical presentation are similar to patients without liver transplantation. The
      etiologies for appendicitis in patients after liver transplantation may be
      different than in those not chronically immunosuppressed, with significantly less
      lymphoid hyperplasia and increased fecalith and cytomegaloviral infections.
      Preliminary results showed that laparoscopic appendectomy after liver
      transplantation results in decreased hospital stays and fewer complications.

PMID- 29321838
TI  - Lung Abscess: An Early Complication of Lung Transplantation in a Patient with
      Cystic Fibrosis.
AB  - A 22-year-old woman with cystic fibrosis (CF) developed lung abscess, as a rare
      complication caused by multidrug-resistant (MDR) Acinetobacter baumannii
      infection, after lung transplantation (LT). After 6 months of long-term
      antibiotic therapy, the abscess was successfully eliminated. In reviewed
      published literature, no previous report was found describing this kind of
      complication caused by MDR A. baumannii in post-LT patient with CF. In our
      experience, lung abscess in LT recipients with CF can be successfully treated
      with prolonged antibiotic therapy.

PMID- 29321839
TI  - Liver Transplantation in a Myopathic Patient with Glycogen Storage Disease Type
      IIIa and Decompensated Cirrhosis.
AB  - Glycogen storage disease (GSD) type IIIa (Forbes-Cori disease) can be associated
      with severe liver disease. A patient with GSD type IIIa may therefore be a
      potential candidate for liver transplantation. Progressive myopathy makes
      uncertain the outcome of the patient and the transplant. Herein, we report on the
      good results of liver transplantation up to 28 months after the transplantation
      in a 40-year-old man with liver cirrhosis and significant muscle weakness due to
      GSD type IIIa.

PMID- 29321840
TI  - Should We Use an Orphan Graft?

PMID- 29321842
TI  - Splenic pedicle control during laparoscopic de-capsulation of a giant splenic
      cyst.
AB  - Splenic cysts are a rare entity in the Western population and are either true
      cysts (primary, 25%) or pseudocysts (secondary, 75%) complicating trauma,
      haemorrhage or infarction. Congenital or simple splenic cysts are the commonest
      primary cysts and surgery is recommended for cysts larger than 5 cm as these are
      prone to infection, bleeding or rupture and for symptomatic or complicated cysts.
      Splenic preservation techniques using the laparoscopic approach are the most
      prevalent. We present a case of a giant painful simple splenic cyst treated with
      laparoscopic de-capsulation with application of a new technique for achieving
      vascular control, whereby control of the splenic pedicle was achieved using a
      Nylon tape. This approach was safe and well tolerated with a total splenic
      ischaemia time of 30 min and a successful result. The patient was discharged with
      no antecedent complications and no recurrence of the cyst at 6 months follow up
      ultrasound scan.

PMID- 29321841
TI  - Reversed gender ratio of autism spectrum disorder in Smith-Magenis syndrome.
AB  - Background: A substantial amount of research shows a higher rate of autistic type
      of problems in males compared to females. The 4:1 male to female ratio is one of
      the most consistent findings in autism spectrum disorder (ASD).Lately, the
      interest in studying ASD in genetic disorders has increased, and research has
      shown a higher prevalence of ASD in some genetic disorders than in the general
      population.Smith-Magenis syndrome (SMS) is a rare and complex genetic syndrome
      caused by an interstitial deletion of chromosome 17p11.2 or a mutation on the
      retinoic acid induced 1 gene. The disorder is characterised by intellectual
      disability, multiple congenital anomalies, obesity, neurobehavioural
      abnormalities and a disrupted circadian sleep-wake pattern. Methods: Parents of
      28 persons with SMS between 5 and 50 years old participated in this study. A
      total of 12 of the persons with SMS were above the age of 18 at the time of the
      study. A total of 11 came from Sweden and 17 were from Norway.We collected
      information regarding the number of autism spectrum symptoms using the Social
      Communication Questionnaire (SCQ) and the Social Responsiveness Scale (SRS).
      Adaptive behaviour was also measured using the Vineland Adaptive Behavior Scale
      II. The level of intellectual disability was derived from a review of the medical
      chart. Results: We found significant gender differences in ASD symptomatology
      using the SCQ and SRS questionnaires. We found approximately three females per
      male above the SCQ cutoff. The same differences were not found in the
      intellectual level and adaptive behaviour or for behavioural and emotional
      problems.Gender had an independent contribution in a regression model predicting
      the total SCQ score, and neither the Vineland Adaptive Behavior Scale II nor the
      Developmental Behaviour Checklist had an independent contribution to the SCQ
      scores. Conclusion: We found a clear reversed gender difference in ASD
      symptomatology in persons with SMS. This may be relevant in the search for female
      protective factors assumed to explain the male bias in ASD.

PMID- 29321843
TI  - Esophagocoloplasty fistula successfully treated with vacuum-assisted closure.
AB  - Esophageal fistulas in the cervical region are usually difficult to manage and
      carry a high morbidity. We report a case of an esophago-colonic fistula after
      colonic interposition, successfully managed with vacuum-assisted closure 'V.A.C.
      system', (Kinetic Concepts Inc., San Antonio, TX, USA). The patient initially
      presented with purulent fluid from the cervical wound 13 days after surgery.
      Esophagogram confirmed a leak. Since the patient had a history of anastomotic
      leaks, a surgical intervention was not the treatment of choice. In light of this,
      conservative treatment with V.A.C. system was initiated. She underwent full
      recovery.

PMID- 29321844
TI  - Foreign body reaction with granuloma following Achilles tendon reconstruction
      with the LARS ligament.
AB  - Ligament reconstruction with the LARS ligament has been a popular choice owing to
      its low-complication rates compared with previously commercially available
      grafts. The non-active nature of the implant also meant that there were no
      foreign body reactions that had been described with other synthetic grafts. We
      describe the first reported case of a granulomatous foreign body reaction in a
      LARS ligament Achilles tendon graft and a technique to reconstruct the tendon
      following its excision.

PMID- 29321845
TI  - Failure to define low back pain as a disease or an episode renders research on
      causality unsuitable: results of a systematic review.
AB  - Background: Causative factors may be different for the very first onset of
      symptoms of the 'disease' of low back pain (LBP) than for ensuing episodes that
      occur after a pain-free period. This differentiation hinges on a life-time
      absence of low back pain at first onset and short-term absence for further
      episodes. In this systematic review, we explored whether researchers make these
      distinctions when investigating the causality of LBP. Methods: A literature
      search of PUBMED, CINAHL, and SCOPUS databases was performed from January 2010
      until September 2016 using the search terms 'low back pain' or 'back pain' and
      'risk factor' or 'caus*' or 'predict*' or 'onset' or 'first-time' or 'inception'
      or 'incidence'. Two reviewers extracted information on study design, types of
      episodes of back pain to distinguish the disease of LBP and recurring episodes,
      and also to determine the definitions of disease- or pain-free periods. Results:
      Thirty-three articles purporting to study causes of LBP were included. Upon
      scrutiny, 31 of the 33 articles were unclear as to what type of causality they
      were studying, that of the 'disease' or the episode, or a mere association with
      LBP. Only 9 studies used a prospective study design. Five studies appeared to
      investigate the onset of the disease of LBP, however, only one study truly
      captured the first incidence of LBP, which was the result of sports injury. Six
      appeared to study episodes but only one clearly related to the concept of
      episodes. Therefore, among those 11 studies, nine included both first-time LBP
      and episodes of LBP. Consequently, 22 studies related to the prevalence of LBP,
      as they probably included a mixture of first-time, recurring and ongoing episodes
      without distinction. Conclusion: Recent literature concerning the causality of
      LBP does not differentiate between the 'disease' of LBP and its recurring
      episodes mainly due to a lack of a clear definition of absence of LBP at
      baseline. Therefore, current research is not capable of providing a valid answer
      on this topic.

PMID- 29321846
TI  - Weak whole-plant trait coordination in a seasonally dry South American stressful
      environment.
AB  - A core question involving both plant physiology and community ecology is whether
      traits from different organs are coordinated across species, beyond pairwise
      trait correlations. The strength of within-community trait coordination has been
      hypothesized to increase along gradients of environmental harshness, due to the
      cost of adopting ecological strategies out of the viable niche space supported by
      the abiotic conditions. We evaluated the strength of trait relationship and
      coordination in a stressful environment using 21 leaf and stem traits of 21
      deciduous and evergreen woody species from a heath vegetation growing on coastal
      sandy plain in northeastern South America. The study region faces marked dry
      season, high soil salinity and acidity, and poor nutritional conditions. Results
      from multiple factor analyses supported two weak and independent axes of trait
      coordination, which accounted for 25%-29% of the trait variance using
      phylogenetically independent contrasts. Trait correlations on the multiple factor
      analyses main axis fit well with the global plant economic spectrum, with species
      investing in small leaves and dense stems as opposed to species with softer stems
      and large leaves. The species' positions on the main functional axis corresponded
      to the competitor-stress-tolerant side of Grime's CSR triangle of plant
      strategies. The weak degree of trait coordination displayed by the heath
      vegetation species contradicted our expectation of high trait coordination in
      stressful environmental habitats. The distinct biogeographic origins of the
      species occurring in the study region and the prevalence of a regional
      environmental filter coupled with local homogeneous conditions could account for
      prevalence of trait independence we observed.

PMID- 29321847
TI  - Search and foraging behaviors from movement data: A comparison of methods.
AB  - Search behavior is often used as a proxy for foraging effort within studies of
      animal movement, despite it being only one part of the foraging process, which
      also includes prey capture. While methods for validating prey capture exist, many
      studies rely solely on behavioral annotation of animal movement data to identify
      search and infer prey capture attempts. However, the degree to which search
      correlates with prey capture is largely untested. This study applied seven
      behavioral annotation methods to identify search behavior from GPS tracks of
      northern gannets (Morus bassanus), and compared outputs to the occurrence of
      dives recorded by simultaneously deployed time-depth recorders. We tested how
      behavioral annotation methods vary in their ability to identify search behavior
      leading to dive events. There was considerable variation in the number of dives
      occurring within search areas across methods. Hidden Markov models proved to be
      the most successful, with 81% of all dives occurring within areas identified as
      search. k-Means clustering and first passage time had the highest rates of dives
      occurring outside identified search behavior. First passage time and hidden
      Markov models had the lowest rates of false positives, identifying fewer search
      areas with no dives. All behavioral annotation methods had advantages and
      drawbacks in terms of the complexity of analysis and ability to reflect prey
      capture events while minimizing the number of false positives and false
      negatives. We used these results, with consideration of analytical difficulty, to
      provide advice on the most appropriate methods for use where prey capture
      behavior is not available. This study highlights a need to critically assess and
      carefully choose a behavioral annotation method suitable for the research
      question being addressed, or resulting species management frameworks established.

PMID- 29321848
TI  - Divergent habitat use of two urban lizard species.
AB  - Faunal responses to anthropogenic habitat modification represent an important
      aspect of global change. In Puerto Rico, two species of arboreal lizard, Anolis
      cristatellus and A. stratulus, are commonly encountered in urban areas, yet seem
      to use the urban habitat in different ways. In this study, we quantified
      differences in habitat use between these two species in an urban setting. For
      each species, we measured habitat use and preference, and the niche space of each
      taxon, with respect to manmade features of the urban environment. To measure
      niche space of these species in an urban environment, we collected data from a
      total of six urban sites across four different municipalities on the island of
      Puerto Rico. We quantified relative abundance of both species, their habitat use,
      and the available habitat in the environment to measure both microhabitat
      preference in an urban setting, as well as niche partitioning between the two
      different lizards. Overall, we found that the two species utilize different
      portions of the urban habitat. Anolis stratulus tends to use more "natural"
      portions of the urban environment (i.e., trees and other cultivated vegetation),
      whereas A. cristatellus more frequently uses anthropogenic structures. We also
      found that aspects of habitat discrimination in urban areas mirror a pattern
      measured in prior studies for forested sites in which A. stratulus was found to
      perch higher than A. cristatellus and preferred lower temperatures and greater
      canopy cover. In our study, we found that the multivariate niche space occupied
      by A. stratulus did not differ from the available niche space in natural portions
      of the urban environment and in turn represented a subset of the niche space
      occupied by A. cristatellus. The unique niche space occupied by A. cristatellus
      corresponds to manmade aspects of the urban environment generally not utilized by
      A. stratulus. Our results demonstrate that some species are merely tolerant of
      urbanization while others utilize urban habitats in novel ways. This finding has
      implications for long-term persistence in urban habitats and suggests that loss
      of natural habitat elements may lead to nonrandom species extirpations as
      urbanization intensifies.

PMID- 29321850
TI  - Bird species richness is associated with phylogenetic relatedness, plant species
      richness, and altitudinal range in Inner Mongolia.
AB  - Bird species richness is mediated by local, regional, and historical factors, for
      example, competition, environmental heterogeneity, contemporary, and historical
      climate. Here, we related bird species richness with phylogenetic relatedness of
      bird assemblages, plant species richness, topography, contemporary climate, and
      glacial-interglacial climate change to investigate the relative importance of
      these factors. This study was conducted in Inner Mongolia, an arid and semiarid
      region with diverse vegetation types and strong species richness gradients. The
      following associated variables were included as follows: phylogenetic relatedness
      of bird assemblages (Net Relatedness Index, NRI), plant species richness,
      altitudinal range, contemporary climate (mean annual temperature and
      precipitation, MAT and MAP), and contemporary-Last Glacial Maximum (LGM) change
      in climate (change in MAT and change in MAP). Ordinary least squares linear,
      simultaneous autoregressive linear, and Random Forest models were used to assess
      the associations between these variables and bird species richness across this
      region. We found that bird species richness was correlated negatively with NRI
      and positively with plant species richness and altitudinal range, with no
      significant correlations with contemporary climate and glacial-interglacial
      climate change. The six best combinations of variables ranked by Random Forest
      models consistently included NRI, plant species richness, and contemporary-LGM
      change in MAT. Our results suggest important roles of local ecological factors in
      shaping the distribution of bird species richness across this semiarid region.
      Our findings highlight the potential importance of these local ecological
      factors, for example, environmental heterogeneity, habitat filtering, and biotic
      interactions, in biodiversity maintenance.

PMID- 29321849
TI  - Population genomics and geographical parthenogenesis in Japanese harvestmen
      (Opiliones, Sclerosomatidae, Leiobunum).
AB  - Naturally occurring population variation in reproductive mode presents an
      opportunity for researchers to test hypotheses regarding the evolution of sex.
      Asexual reproduction frequently assumes a geographical pattern, in which
      parthenogenesis-dominated populations are more broadly dispersed than their
      sexual conspecifics. We evaluate the geographical distribution of genomic
      signatures associated with parthenogenesis using nuclear and mitochondrial DNA
      sequence data from two Japanese harvestman sister taxa, Leiobunum manubriatum and
      Leiobunum globosum. Asexual reproduction is putatively facultative in these
      species, and female-biased localities are common in habitat margins. Past
      karyotypic and current cytometric work indicates L. globosum is entirely
      tetraploid, while L. manubriatum may be either diploid or tetraploid. We
      estimated species phylogeny, genetic differentiation, diversity, and mitonuclear
      discordance in females collected across the species range in order to identify
      range expansion toward marginal habitat, potential for hybrid origin, and
      persistence of asexual lineages. Our results point to northward expansion of a
      tetraploid ancestor of L. manubriatum and L. globosum, coupled with support for
      greater male gene flow in southern L. manubriatum localities. Specimens from
      localities in the Tohoku and Hokkaido regions were indistinct, particularly those
      of L. globosum, potentially due to little mitochondrial differentiation or
      haplotypic variation. Although L. manubriatum overlaps with L. globosum across
      its entire range, L. globosum was reconstructed as monophyletic with strong
      support using mtDNA, and marginal support with nuclear loci. Ultimately, we find
      evidence for continued sexual reproduction in both species and describe
      opportunities to clarify the rate and mechanism of parthenogenesis.

PMID- 29321851
TI  - Specificity of herbivore-induced responses in an invasive species, Alternanthera
      philoxeroides (alligator weed).
AB  - Herbivory-induced responses in plants can both negatively affect subsequently
      colonizing herbivores and mitigate the effect of herbivory on the host. However,
      it is still less known whether plants exhibit specific responses to specialist
      and generalist herbivores in non-secondary metabolite traits and how specificity
      to specialists and generalists differs between invasive and native plant
      populations. We exposed an invasive plant, Alternanthera philoxeroides, to
      Agasicles hygrophila (Coleoptera, Chrysomelidae; specialist), Spodoptera litura
      (Lepidoptera, Noctuidae; generalist), manual clipping, or application of
      exogenous jasmonic acid and examined both the specificity of elicitation in
      traits of fitness (e.g., aboveground biomass), morphology (e.g., root:shoot
      ratio), and chemistry (e.g., C/N ratio and lignin), and specificity of effect on
      the subsequent performance of A. hygrophila and S. litura. Then, we assessed
      variation of the specificity between invasive and native populations (USA and
      Argentina, respectively). The results showed S. litura induced higher branching
      intensity and specific leaf area but lower C/N ratio than A. hygrophila, whereas
      A. hygrophila induced higher trichome density than S. litura. The negative effect
      of induction on subsequent larval growth was greater for S. litura than for A.
      hygrophila. Invasive populations had a weaker response to S. litura than to A.
      hygrophila in triterpenoid saponins and C/N ratio, while native populations
      responded similarly to these two herbivores. The specific effect on the two
      herbivores feeding on induced plants did not vary between invasive and native
      populations. Overall, we demonstrate specificity of elicitation to specialist and
      generalist herbivores in non-secondary metabolite traits, and that the generalist
      is more susceptible to induction than the specialist. Furthermore, chemical
      responses specific to specialist and generalist herbivores only exist in the
      invasive populations, consistent with an evolutionary change in specificity in
      the invasive populations.

PMID- 29321852
TI  - Ignorance can be evolutionarily beneficial.
AB  - Information is increasingly being viewed as a resource used by organisms to
      increase their fitness. Indeed, it has been formally shown that there is a
      sensible way to assign a reproductive value to information and it is non
      negative. However, all of this work assumed that information collection is cost
      free. Here, we account for such a cost and provide conditions for when the
      reproductive value of information will be negative. In these instances,
      counterintuitively, it is in the interest of the organism to remain ignorant. We
      link our results to empirical studies where Bayesian behavior appears to break
      down in complex environments and provide an alternative explanation of lowered
      arousal thresholds in the evolution of sleep.

PMID- 29321853
TI  - Tracking plant preference for higher-quality mycorrhizal symbionts under varying
      CO2 conditions over multiple generations.
AB  - The symbiosis between plants and root-colonizing arbuscular mycorrhizal (AM)
      fungi is one of the most ecologically important examples of interspecific
      cooperation in the world. AM fungi provide benefits to plants; in return plants
      allocate carbon resources to fungi, preferentially allocating more resources to
      higher-quality fungi. However, preferential allocations from plants to symbionts
      may vary with environmental context, particularly when resource availability
      affects the relative value of symbiotic services. We ask how differences in
      atmospheric CO 2-levels influence root colonization dynamics between AMF species
      that differ in their quality as symbiotic partners. We find that with increasing
      CO 2-conditions and over multiple plant generations, the more beneficial fungal
      species is able to achieve a relatively higher abundance. This suggests that
      increasing atmospheric carbon supply enables plants to more effectively allocate
      carbon to higher-quality mutualists, and over time helps reduce lower-quality AM
      abundance. Our results illustrate how environmental context may affect the extent
      to which organisms structure interactions with their mutualistic partners and
      have potential implications for mutualism stability and persistence under global
      change.

PMID- 29321854
TI  - Phylogenetic relationships and phylogeography of relevant lineages within the
      complex Campanulaceae family in Macaronesia.
AB  - Macaronesia has long been recognized as a natural model for studying evolutionary
      processes in plant diversification. Several studies have attempted to focus on
      single lineages, and few have covered the diversification of a family across all
      the archipelagos. We used a comprehensive sample to clarify the phylogenetic
      relationships and the biogeographic history of the Macaronesian Campanulaceae.
      Hypotheses related to the colonization of these archipelagos will be used to
      examine the diversification patterns of different lineages. We sequenced the ITS
      region and six cpDNA markers (atpB, matK, petD, rbcL, trnL-F, and psbA-trnH) from
      10 Campanulaceae species, including seven endemic species in Macaronesia. The
      phylogeny of these taxa was reconstructed using maximum parsimony, maximum
      likelihood, and Bayesian inference. To study the relationships within each
      lineage, haplotype networks were calculated using NeighborNet and TCS algorithms.
      Moreover, data were combined with fossil information to construct time-calibrated
      trees for the Macaronesian Campanulaceae species. The phylogenetic analyses are
      largely congruent with current taxon circumscriptions, and all the endemic genera
      formed monophyletic clades, namely Azorina in Azores; Musschia in Madeira; and
      Campanula in Cape Verde. The Azorina clade and the Cape Verde endemic Campanula
      may share a common ancestor in North Africa, and the divergence was dated ca.
      12.3 million years ago (Mya). The divergence of the Musschia clade began in the
      Pliocene ca. 3.4 Mya. Moreover, several examples of intraspecific variation were
      revealed among the native species with a clear geographic structured patterns,
      suggesting that cryptic diversity might exist within the native Macaronesian
      Campanulaceae when compared to the close mainland taxa (e.g., Campanula erinus,
      Trachelium caeruleum), but additional studies are needed to support the molecular
      data. This study highlights the power of combining data (e.g., phylogeny and
      divergence times, with species distribution data) for testing diversification
      hypotheses within the unique Macaronesian flora, providing useful information for
      future conservation efforts.

PMID- 29321855
TI  - Hunting-mediated predator facilitation and superadditive mortality in a European
      ungulate.
AB  - Predator-prey theory predicts that in the presence of multiple types of predators
      using a common prey, predator facilitation may result as a consequence of
      contrasting prey defense mechanisms, where reducing the risk from one predator
      increases the risk from the other. While predator facilitation is well
      established in natural predator-prey systems, little attention has been paid to
      situations where human hunters compete with natural predators for the same prey.
      Here, we investigate hunting-mediated predator facilitation in a hunter-predator
      prey system. We found that hunter avoidance by roe deer (Capreolus capreolus)
      exposed them to increase predation risk by Eurasian lynx (Lynx lynx). Lynx
      responded by increasing their activity and predation on deer, providing evidence
      that superadditive hunting mortality may be occurring through predator
      facilitation. Our results reveal a new pathway through which human hunters, in
      their role as top predators, may affect species interactions at lower trophic
      levels and thus drive ecosystem processes.

PMID- 29321856
TI  - Temporal effects of disturbance on community composition in simulated stage
      structured plant communities.
AB  - In an era of global environmental change, understanding how disturbance affects
      the dynamics of ecological communities is crucial. However, few studies have
      theoretically explored the potential influence of disturbance including both
      intensity and frequency on compositional change over time in communities with
      stage structure. A spatially explicit, individual-based model was constructed
      incorporating the various demographic responses to disturbance of plants at two
      different growth stages: seedlings and adults. In the model, we assumed that
      individuals within each stage were demographically equivalent (neutral) but
      differed between stages. We simulated a common phenomenon that seedlings suffered
      more from disturbance such as grazing and fire than adults. We showed how stage
      structured communities of seedlings and adults responded to disturbance with
      various levels of disturbance frequency and intensity. In "undisturbed"
      simulations, the relationship between average species abundance (defined here as
      the total number of individuals divided by species richness) and community
      composition turnover (measured by the Bray-Curtis similarity index) was
      asymptotic. However, in strongly "disturbed" simulations with the between
      disturbance intervals greater than one, this relationship became unimodal. Stage
      dependent response to disturbance underlay the above discrepancy between
      undisturbed and disturbed communities.

PMID- 29321857
TI  - A holistic approach to determine tree structural complexity based on laser
      scanning data and fractal analysis.
AB  - The three-dimensional forest structure affects many ecosystem functions and
      services provided by forests. As forests are made of trees it seems reasonable to
      approach their structure by investigating individual tree structure. Based on
      three-dimensional point clouds from laser scanning, a newly developed holistic
      approach is presented that enables to calculate the box dimension as a measure of
      structural complexity of individual trees using fractal analysis. It was found
      that the box dimension of trees was significantly different among the tested
      species, among trees belonging to the same species but exposed to different
      growing conditions (at gap vs. forest interior) or to different kinds of
      competition (intraspecific vs. interspecific). Furthermore, it was shown that the
      box dimension is positively related to the trees' growth rate. The box dimension
      was identified as an easy to calculate measure that integrates the effect of
      several external drivers of tree structure, such as competition strength and
      type, while simultaneously providing information on structure-related properties,
      like tree growth.

PMID- 29321858
TI  - How do steppe plants follow their optimal environmental conditions or persist
      under suboptimal conditions? The differing strategies of annuals and perennials.
AB  - For a species to be able to respond to environmental change, it must either
      succeed in following its optimal environmental conditions or in persisting under
      suboptimal conditions, but we know very little about what controls these
      capacities. We parameterized species distribution models (SDMs) for 135 plant
      species from the Algerian steppes. We interpreted low false-positive rates as
      reflecting a high capacity to follow optimal environmental conditions and high
      false-negative rates as a high capacity to persist under suboptimal environmental
      conditions. We also measured functional traits in the field and built a unique
      plant trait database for the North-African steppe. For both perennial and annual
      species, we explored how these two capacities can be explained by species traits
      and whether relevant trait values reflect species strategies or biases in SDMs.
      We found low false-positive rates in species with small seeds, flowers attracting
      specialist pollinators, and specialized distributions (among annuals and
      perennials), low root:shoot ratios, wide root-systems, and large leaves
      (perennials only) (R2 = .52-58). We found high false-negative rates in species
      with marginal environmental distribution (among annuals and perennials), small
      seeds, relatively deep roots, and specialized distributions (annuals) or large
      leaves, wide root-systems, and monocarpic life cycle (perennials) (R2 = .38 for
      annuals and 0.65 for perennials). Overall, relevant traits are rarely indicative
      of the possible biases of SDMs, but rather reflect the species' reproductive
      strategy, dispersal ability, stress tolerance, and pollination strategies. Our
      results suggest that wide undirected dispersal in annual species and efficient
      resource acquisition in perennial species favor both capacities, whereas short
      life spans in perennial species favor persistence in suboptimal environmental
      conditions and flowers attracting specialist pollinators in perennial and annual
      species favor following optimal environmental conditions. Species that neither
      follow nor persist will be at risk under future environmental change.

PMID- 29321859
TI  - Habitat-related seed germination traits in alpine habitats.
AB  - Understanding the key aspects of plant regeneration from seeds is crucial in
      assessing species assembly to their habitats. However, the regenerative traits of
      seed dormancy and germination are underrepresented in this context. In the alpine
      zone, the large species and microhabitat diversity provide an ideal context to
      assess habitat-related regenerative strategies. To this end, seeds of 53 species
      growing in alpine siliceous and calcareous habitats (6230 and 6170 of EU
      Directive 92/43, respectively) were exposed to different temperature treatments
      under controlled laboratory conditions. Germination strategies in each habitat
      were identified by clustering with k-means. Then, phylogenetic least squares
      correlations (PGLS) were fitted to assess germination and dormancy differences
      between species' main habitat (calcareous and siliceous), microhabitat
      (grasslands, heaths, rocky, and species with no specific microhabitats), and
      chorology (arctic-alpine and continental). Calcareous and siliceous grasslands
      significantly differ in their germination behaviour with a slow, mostly
      overwinter germination and high germination under all conditions, respectively.
      Species with high overwinter germination occurs mostly in heaths and have an
      arctic-alpine distribution. Meanwhile, species with low or high germinability in
      general inhabit in grasslands or have no specific microhabitat (they belong to
      generalist), respectively. Alpine species use different germination strategies
      depending on habitat provenance, species' main microhabitat, and chorotype. Such
      differences may reflect adaptations to local environmental conditions and
      highlight the functional role of germination and dormancy in community ecology.

PMID- 29321860
TI  - Incorporating variability in simulations of seasonally forced phenology using
      integral projection models.
AB  - Phenology models are becoming increasingly important tools to accurately predict
      how climate change will impact the life histories of organisms. We propose a
      class of integral projection phenology models derived from stochastic individual
      based models of insect development and demography. Our derivation, which is based
      on the rate summation concept, produces integral projection models that capture
      the effect of phenotypic rate variability on insect phenology, but which are
      typically more computationally frugal than equivalent individual-based phenology
      models. We demonstrate our approach using a temperature-dependent model of the
      demography of the mountain pine beetle (Dendroctonus ponderosae Hopkins), an
      insect that kills mature pine trees. This work illustrates how a wide range of
      stochastic phenology models can be reformulated as integral projection models.
      Due to their computational efficiency, these integral projection models are
      suitable for deployment in large-scale simulations, such as studies of altered
      pest distributions under climate change.

PMID- 29321861
TI  - Low interannual precipitation has a greater negative effect than seedling
      herbivory on the population dynamics of a short-lived shrub, Schiedea obovata.
AB  - Climate projections forecast more extreme interannual climate variability over
      time, with an increase in the severity and duration of extreme drought and
      rainfall events. Based on bioclimatic envelope models, it is projected that
      changing precipitation patterns will drastically alter the spatial distributions
      and density of plants and be a primary driver of biodiversity loss. However, many
      other underlying mechanisms can impact plant vital rates (i.e., survival, growth,
      and reproduction) and population dynamics. In this study, we developed a size
      dependent integral projection model (IPM) to evaluate how interannual
      precipitation and mollusk herbivory influence the dynamics of a Hawaii endemic
      short-lived shrub, Schiedea obovata (Caryophyllaceae). Assessing how wet season
      precipitation effects population dynamics it critical, as it is the timeframe
      when most of the foliar growth occurs, plants flower and fruit, and seedlings
      establish. Temporal variation in wet season precipitation had a greater effect
      than mollusk herbivory on S. obovata population growth rate lambda, and the
      impact of interannual precipitation on vital rates shifted across plant ontogeny.
      Furthermore, wet season precipitation influenced multiple vital rates in
      contrasting ways and the effect of precipitation on the survival of larger
      vegetative and reproductively mature individuals contributed the most to
      variation in the population growth rate. Among all combination of wet season
      precipitation and herbivory intensities, the only scenario that led to a growing
      population was when high wet precipitation was associated with low herbivory. Our
      study highlights the importance of evaluating how abiotic factors and plant
      consumer interactions influence an organism across its life cycle to fully
      understand the underpinning mechanisms that structure its spatial and temporal
      distribution and abundance. Our results also illustrate that for short-lived
      species, like S. obovata, seedling herbivory can have less of an effect on the
      dynamics of plant populations than decreased interannual precipitation.

PMID- 29321862
TI  - Assessing the utility of metabarcoding for diet analyses of the omnivorous wild
      pig (Sus scrofa).
AB  - Wild pigs (Sus scrofa) are an invasive species descended from both domestic swine
      and Eurasian wild boar that was introduced to North America during the early
      1500s. Wild pigs have since become the most abundant free-ranging exotic ungulate
      in the United States. Large and ever-increasing populations of wild pigs
      negatively impact agriculture, sport hunting, and native ecosystems with costs
      estimated to exceed $1.5 billion/year within the United States. Wild pigs are
      recognized as generalist feeders, able to exploit a broad array of locally
      available food resources, yet their feeding behaviors remain poorly understood as
      partially digested material is often unidentifiable through traditional stomach
      content analyses. To overcome the limitation of stomach content analyses, we
      developed a DNA sequencing-based protocol to describe the plant and animal diet
      composition of wild pigs. Additionally, we developed and evaluated blocking
      primers to reduce the amplification and sequencing of host DNA, thus providing
      greater returns of sequences from diet items. We demonstrate that the use of
      blocking primers produces significantly more sequencing reads per sample from
      diet items, which increases the robustness of ascertaining animal diet
      composition with molecular tools. Further, we show that the overall plant and
      animal diet composition is significantly different between the three areas
      sampled, demonstrating this approach is suitable for describing differences in
      diet composition among the locations.

PMID- 29321863
TI  - Impact of moderate and extreme climate change scenarios on growth, morphological
      features, photosynthesis, and fruit production of hot pepper.
AB  - Horticultural crop production and changes in physiological aspects during the
      growing season may be affected by climate change factors (CC), which include
      increased temperature and the associated doubling or tripling of atmospheric CO2
      concentrations. However, the potential effects are complex and many parameters
      might impact on the observed effects. To evaluate the effects of CC, the growth,
      yield, fruit characteristics, photosynthetic traits, and morphological
      characteristics of hot peppers were investigated. The hot peppers were grown
      under two CC scenarios, with the Representative Concentration Pathway (RCP) of
      4.5 (Temp.; +3.4 degrees C, CO2 conc.; 540 MUmol/mol, Precipitation +17.3%) and
      RCP 8.5 (Temp.; +6.0 degrees C and CO2 conc.; 940 MUmol/mol, Precipitation
      +20.3%), respectively, using extreme weather simulators. This was compared with
      existing weather conditions occurring in Jeonju, South Korea in terms of air
      temperature, relative humidity, radiation, and precipitation. Overall, the plant
      height showed the highest under moderate CC conditions (RCP 4.5) among all the
      treatments tested. The number of leaves in the RCP 8.5 condition showed
      7,739/plants, which was 2.2 times higher than that of the control. In addition,
      fruit shape was shortened and percentage dry matter was also the highest. The
      yield of hot pepper in the CC RCP 4.5 and 8.5 conditions were decreased by 21.5%
      and 89.2% when compared with that of the control, respectively. The days to
      harvest in the condition of CC scenarios were shortened from 5 to 13 compared
      with that of control, predominantly due to the increased air temperature. The
      results indicated that the severe RCP CC scenarios made reduction in the yields
      and negative affection on the fruit qualities. Overall, hot pepper was tolerant
      of mild CC scenarios of temperature * CO2 but was significantly affected by more
      extreme CC interacting parameter concentrations (or similar).

PMID- 29321864
TI  - The evolution of sexes: A specific test of the disruptive selection theory.
AB  - The disruptive selection theory of the evolution of anisogamy posits that the
      evolution of a larger body or greater organismal complexity selects for a larger
      zygote, which in turn selects for larger gametes. This may provide the
      opportunity for one mating type to produce more numerous, small gametes, forcing
      the other mating type to produce fewer, large gametes. Predictions common to this
      and related theories have been partially upheld. Here, a prediction specific to
      the disruptive selection theory is derived from a previously published game
      theoretic model that represents the most complete description of the theory. The
      prediction, that the ratio of macrogamete to microgamete size should be above
      three for anisogamous species, is supported for the volvocine algae. A fully
      population genetic implementation of the model, involving mutation, genetic
      drift, and selection, is used to verify the game-theoretic approach and
      accurately simulates the evolution of gamete sizes in anisogamous species. This
      model was extended to include a locus for gamete motility and shows that oogamy
      should evolve whenever there is costly motility. The classic twofold cost of sex
      may be derived from the fitness functions of these models, showing that this cost
      is ultimately due to genetic conflict.

PMID- 29321865
TI  - Responses of soil respiration to soil management changes in an agropastoral
      ecotone in Inner Mongolia, China.
AB  - Studying the responses of soil respiration (Rs) to soil management changes is
      critical for enhancing our understanding of the global carbon cycle and has
      practical implications for grassland management. Therefore, the objectives of
      this study were (1) quantify daily and seasonal patterns of Rs, (2) evaluate the
      influence of abiotic factors on Rs, and (3) detect the effects of soil management
      changes on Rs. We hypothesized that (1) most of daily and seasonal variation in
      Rs could be explained by soil temperature (Ts) and soil water content (Sw), (2)
      soil management changes could significantly affect Rs, and (3) soil management
      changes affected Rs via the significant change in abiotic and biotic factors. In
      situ Rs values were monitored in an agropastoral ecotone in Inner Mongolia,
      China, during the growing seasons in 2009 (August to October) and 2010 (May to
      October). The soil management changes sequences included free grazing grassland
      (FG), cropland (CL), grazing enclosure grassland (GE), and abandoned cultivated
      grassland (AC). During the growing season in 2010, cumulative Rs for FG, CL, GE,
      and AC averaged 265.97, 344.74, 236.70, and 226.42 gC m-2 year-1, respectively.
      The Ts and Sw significantly influenced Rs and explained 66%-86% of the
      variability in daily Rs. Monthly mean temperature and precipitation explained 78%
      96% of the variability in monthly Rs. The results clearly showed that Rs was
      increased by 29% with the conversion of FG to CL and decreased by 35% and 11%
      with the conversion of CL to AC and FG to GE. The factors impacting the change in
      Rs under different soil management changes sequences varied. Our results confirm
      the tested hypotheses. The increase in Q10 and litter biomass induced by
      conversion of FG to GE could lead to increased Rs if the climate warming. We
      suggest that after proper natural restoration period, grasslands should be
      utilized properly to decrease Rs.

PMID- 29321866
TI  - Grazing weakens temporal stabilizing effects of diversity in the Eurasian steppe.
AB  - Many biodiversity experiments have demonstrated that plant diversity can
      stabilize productivity in experimental grasslands. However, less is known about
      how diversity-stability relationships are mediated by grazing. Grazing is known
      for causing species losses, but its effects on plant functional groups (PFGs)
      composition and species asynchrony, which are closely correlated with ecosystem
      stability, remain unclear. We conducted a six-year grazing experiment in a semi
      arid steppe, using seven levels of grazing intensity (0, 1.5, 3.0, 4.5, 6.0, 7.5,
      and 9.0 sheep per hectare) and two grazing systems (i.e., a traditional,
      continuous grazing system during the growing period (TGS), and a mixed one
      rotating grazing and mowing annually (MGS)), to examine the effects of grazing
      system and grazing intensity on the abundance and composition of PFGs and
      diversity-stability relationships. Ecosystem stability was similar between mixed
      and continuous grazing treatments. However, within the two grazing systems,
      stability was maintained through different pathways, that is, along with grazing
      intensity, persistence biomass variations in MGS, and compensatory interactions
      of PFGs in their biomass variations in TGS. Ecosystem temporal stability was not
      decreased by species loss but rather remain unchanged by the strong compensatory
      effects between PFGs, or a higher grazing-induced decrease in species asynchrony
      at higher diversity, and a higher grazing-induced increase in the temporal
      variation of productivity in diverse communities. Ecosystem stability of
      aboveground net primary production was not related to species richness in both
      grazing systems. High grazing intensity weakened the temporal stabilizing effects
      of diversity in this semi-arid grassland. Our results demonstrate that the
      productivity of dominant PFGs is more important than species richness for
      maximizing stability in this system. This study distinguishes grazing intensity
      and grazing system from diversity effects on the temporal stability, highlighting
      the need to better understand how grazing regulates ecosystem stability, plant
      diversity, and their synergic relationships.

PMID- 29321867
TI  - High site fidelity and restricted ranging patterns in southern Australian
      bottlenose dolphins.
AB  - Information on site fidelity and ranging patterns of wild animals is critical to
      understand how they use their environment and guide conservation and management
      strategies. Delphinids show a wide variety of site fidelity and ranging patterns.
      Between September 2013 and October 2015, we used boat-based surveys, photographic
      identification, biopsy sampling, clustering analysis, and geographic information
      systems to determine the site-fidelity patterns and representative ranges of
      southern Australian bottlenose dolphins (Tursiops cf. australis) inhabiting the
      inner area of Coffin Bay, a highly productive inverse estuary located within
      Thorny Passage Marine Park, South Australia. Agglomerative hierarchical
      clustering (AHC) of individuals' site-fidelity index and sighting rates indicated
      that the majority of dolphins within the inner area of Coffin Bay are "regular
      residents" (n = 125), followed by "occasional residents" (n = 28), and
      "occasional visitors" (n = 26). The low standard distance deviation indicated
      that resident dolphins remained close to their main center of use (range = 0.7
      4.7 km, X +/- SD = 2.3 +/- 0.9 km). Representative ranges of resident dolphins
      were small (range = 3.9-33.5 km2, X +/- SD = 15.2 +/- 6.8 km2), with no
      significant differences between males and females (Kruskal-Wallis, chi2 = 0.426,
      p = .808). The representative range of 56% of the resident dolphins was
      restricted to a particular bay within the study area. The strong site fidelity
      and restricted ranging patterns among individuals could be linked to the high
      population density of this species in the inner area of Coffin Bay, coupled with
      differences in social structure and feeding habits. Our results emphasize the
      importance of productive habitats as a major factor driving site fidelity and
      restricted movement patterns in highly mobile marine mammals and the high
      conservation value of the inner area of Coffin Bay for southern Australian
      bottlenose dolphins.

PMID- 29321868
TI  - Global mtDNA genetic structure and hypothesized invasion history of a major pest
      of citrus, Diaphorina citri (Hemiptera: Liviidae).
AB  - The Asian citrus psyllid Diaphorina citri Kuwayama is a key pest of citrus as the
      vector of the bacterium causing the "huanglongbing" disease (HLB). To assess the
      global mtDNA population genetic structure, and possible dispersal history of the
      pest, we investigated genetic variation at the COI gene collating newly collected
      samples with all previously published data. Our dataset consists of 356 colonies
      from 106 geographic sites worldwide. High haplotype diversity (H-mean = 0.702 +/-
      0.017), low nucleotide diversity (pi-mean = 0.003), and significant positive
      selection (Ka/Ks = 32.92) were observed. Forty-four haplotypes (Hap) were
      identified, clustered into two matrilines: Both occur in southeastern and
      southern Asia, North and South America, and Africa; lineages A and B also occur
      in eastern and western Asia, respectively. The most abundant haplotypes were Hap4
      in lineage A (35.67%), and Hap9 in lineage B (41.29%). The haplotype network
      identified them as the ancestral haplotypes within their respective lineages.
      Analysis of molecular variance showed significant genetic structure (FST = 0.62,
      p < .0001) between the lineages, and population genetic analysis suggests
      geographic structuring. We hypothesize a southern and/or southeastern Asia
      origin, three dispersal routes, and parallel expansions of two lineages. The
      hypothesized first route involved the expansion of lineage B from southern Asia
      into North America via West Asia. The second, the expansion of some lineage A
      individuals from Southeast Asia into East Asia, and the third involved both
      lineages from Southeast Asia spreading westward into Africa and subsequently into
      South America. To test these hypotheses and gain a deeper understanding of the
      global history of D. citri, more data-rich approaches will be necessary from the
      ample toolkit of next-generation sequencing (NGS). However, this study may serve
      to guide such sampling and in the development of biological control programs
      against the global pest D. citri.

PMID- 29321869
TI  - Imitating the cost of males: A hypothesis for coexistence of all-female sperm
      dependent species and their sexual host.
AB  - All-female sperm-dependent species are particular asexual organisms that must
      coexist with a closely related sexual host for reproduction. However, demographic
      advantages of asexual over sexual species that have to produce male individuals
      could lead both to extinction. The unresolved question of their coexistence still
      challenges and fascinates evolutionary biologists. As an alternative hypothesis,
      we propose those asexual organisms are afflicted by a demographic cost analogous
      to the production of males to prevent exclusion of the host. Previously proposed
      hypotheses stated that asexual individuals relied on a lower fecundity than
      sexual females to cope with demographic advantage. In contrast, we propose that
      both sexual and asexual species display the same number of offspring, but half of
      asexual individuals imitate the cost of sex by occupying ecological niches but
      producing no offspring. Simulations of population growth in closed systems under
      different demographic scenarios revealed that only the presence of
      nonreproductive individuals in asexual females can result in long-term
      coexistence. This hypothesis is supported by the fact that half of the females in
      some sperm-dependent organisms did not reproduce clonally.

PMID- 29321871
TI  - Leaf trait variations associated with habitat affinity of tropical karst tree
      species.
AB  - Karst hills, that is, jagged topography created by dissolution of limestone and
      other soluble rocks, are distributed extensively in tropical forest regions,
      including southern parts of China. They are characterized by a sharp mosaic of
      water and nutrient availability, from exposed hilltops with poor soil development
      to valleys with occasional flooding, to which trees show species-specific
      distributions. Here we report the relationship of leaf functional traits to
      habitat preference of tropical karst trees. We described leaf traits of 19
      tropical tree species in a seasonal karst rainforest in Guangxi Province, China,
      12 species in situ and 13 ex situ in a non-karst arboretum, which served as a
      common garden, with six species sampled in both. We examined how the measured
      leaf traits differed in relation to species' habitat affinity and evaluated trait
      consistency between natural habitats vs. the arboretum. Leaf mass per area (LMA)
      and optical traits (light absorption and reflectance characteristics between 400
      and 1,050 nm) showed significant associations with each other and habitats, with
      hilltop species showing high values of LMA and low values of photochemical
      reflectance index (PRI). For the six species sampled in both the karst forest and
      the arboretum, LMA, leaf dry matter content, stomatal density, and vein length
      per area showed inconsistent within-species variations, whereas some traits
      (stomatal pore index and lamina thickness) were similar between the two sites. In
      conclusion, trees specialized in exposed karst hilltops with little soils are
      characterized by thick leaves with high tissue density indicative of conservative
      resources use, and this trait syndrome could potentially be sensed remotely with
      PRI.

PMID- 29321870
TI  - Contrasting genetic metrics and patterns among naturalized rainbow trout
      (Oncorhynchus mykiss) in two Patagonian lakes differentially impacted by trout
      aquaculture.
AB  - Different pathways of propagation and dispersal of non-native species into new
      environments may have contrasting demographic and genetic impacts on established
      populations. Repeated introductions of rainbow trout (Oncorhynchus mykiss) to
      Chile in South America, initially through stocking and later through aquaculture
      escapes, provide a unique setting to contrast these two pathways. Using a panel
      of single nucleotide polymorphisms, we found contrasting genetic metrics and
      patterns among naturalized trout in Lake Llanquihue, Chile's largest producer of
      salmonid smolts for nearly 50 years, and Lake Todos Los Santos (TLS), a reference
      lake where aquaculture has been prohibited by law. Trout from Lake Llanquihue
      showed higher genetic diversity, weaker genetic structure, and larger estimates
      for the effective number of breeders (Nb) than trout from Lake TLS. Trout from
      Lake TLS were divergent from Lake Llanquihue and showed marked genetic structure
      and a significant isolation-by-distance pattern consistent with secondary contact
      between documented and undocumented stocking events in opposite shores of the
      lake. Multiple factors, including differences in propagule pressure, origin of
      donor populations, lake geomorphology, habitat quality or quantity, and life
      history, may help explain contrasting genetic metrics and patterns for trout
      between lakes. We contend that high propagule pressure from aquaculture may not
      only increase genetic diversity and Nb via demographic effects and admixture, but
      also may impact the evolution of genetic structure and increase gene flow,
      consistent with findings from artificially propagated salmonid populations in
      their native and naturalized ranges.

PMID- 29321872
TI  - Relative contribution of neutral and deterministic processes in shaping fruit
      feeding butterfly assemblages in Afrotropical forests.
AB  - The unified neutral theory of biodiversity and biogeography has gained the status
      of a quantitative null model for explaining patterns in ecological
      (meta)communities. The theory assumes that individuals of trophically similar
      species are functionally equivalent. We empirically evaluate the relative
      contribution of neutral and deterministic processes in shaping fruit-feeding
      butterfly assemblages in three tropical forests in Africa, using both direct
      (confronting the neutral model with species abundance data) and indirect
      approaches (testing the predictions of neutral theory using data other than
      species abundance distributions). Abundance data were obtained by sampling
      butterflies using banana baited traps set at the forest canopy and understorey
      strata. Our results indicate a clear consistency in the kind of species or
      species groups observed at either the canopy or understorey in the three studied
      communities. Furthermore, we found significant correlation between some flight
      related morphological traits and species abundance at the forest canopy, but not
      at the understorey. Neutral theory's contribution to explaining our data lies
      largely in identifying dispersal limitation as a key process regulating fruit
      feeding butterfly community structure. Our study illustrates that using species
      abundance data alone in evaluating neutral theory can be informative, but is
      insufficient. Species-level information such as habitat preference, host plants,
      geographical distribution, and phylogeny is essential in elucidating the
      processes that regulate biodiversity community structures and patterns.

PMID- 29321873
TI  - Identifying compartments in ecological networks based on energy channels.
AB  - It has been confirmed in many food webs that the interactions between species are
      divided into "compartments," that is, subgroups of highly interacting taxa with
      few weak interactions between the subgroups. Many of the current methods for
      detecting compartments in food webs are borrowed from network theory, which do
      little to improve our understanding of the mechanisms underpinning them.
      Therefore, a method based on ecological context is needed. Here, we develop a new
      method for detecting compartments in food webs based on the reliance of each node
      on energy derived from basal resources (i.e., producers or decomposers).
      Additional Monte Carlo simulations were conducted to test the significance of the
      compartmentalization. Further, we applied a food web dynamics model to test
      whether the effects of permutation would be retained within a single compartment.
      The proposed method identified significant compartments in 23 of the 28 empirical
      food webs that were investigated. We further demonstrated that the effects of
      node removal were significantly higher within compartments than between
      compartments. Our methods and results emphasize the importance of energy channels
      in forming food web structures, which sheds light on the mechanisms of self
      organization within food webs.

PMID- 29321874
TI  - Conservation planning for freshwater-marine carryover effects on Chinook salmon
      survival.
AB  - Experiences of migratory species in one habitat may affect their survival in the
      next habitat, in what is known as carryover effects. These effects are especially
      relevant for understanding how freshwater experience affects survival in
      anadromous fishes. Here, we study the carryover effects of juvenile salmon
      passage through a hydropower system (Snake and Columbia rivers, northwestern
      United States). To reduce the direct effect of hydrosystem passage on juveniles,
      some fishes are transported through the hydrosystem in barges, while the others
      are allowed to migrate in-river. Although hydrosystem survival of transported
      fishes is greater than that of their run-of-river counterparts, their relative
      juvenile-to-adult survival (hereafter survival) can be less. We tested for
      carryover effects using generalized linear mixed effects models of survival with
      over 1 million tagged Chinook salmon, Oncorhynchus tshawytscha (Walbaum)
      (Salmonidae), migrating in 1999-2013. Carryover effects were identified with rear
      type (wild vs. hatchery), passage-type (run-of-river vs. transported), and
      freshwater and marine covariates. Importantly, the Pacific Decadal Oscillation
      (PDO) index characterizing cool/warm (i.e., productive/nonproductive) ocean
      phases had a strong influence on the relative survival of rear- and passage
      types. Specifically, transportation benefited wild Chinook salmon more in cool
      PDO years, while hatchery counterparts benefited more in warm PDO years.
      Transportation was detrimental for wild Chinook salmon migrating early in the
      season, but beneficial for later season migrants. Hatchery counterparts benefited
      from transportation throughout the season. Altogether, wild fish could benefit
      from transportation approximately 2 weeks earlier during cool PDO years, with
      still a benefit to hatchery counterparts. Furthermore, we found some support for
      hypotheses related to higher survival with increased river flow, high predation
      in the estuary and plume areas, and faster migration and development-related
      increased survival with temperature. Thus, pre- and within-season information on
      local- and broad-scale conditions across habitats can be useful for planning and
      implementing real-time conservation programs.

PMID- 29321875
TI  - Drivers of apoplastic freezing in gymnosperm and angiosperm branches.
AB  - It is not well understood what determines the degree of supercooling of
      apoplastic sap in trees, although it determines the number and duration of annual
      freeze-thaw cycles in a given environment. We studied the linkage between
      apoplastic ice nucleation temperature, tree water status, and conduit size. We
      used branches of 10 gymnosperms and 16 angiosperms collected from an arboretum in
      Helsinki (Finland) in winter and spring. Branches with lower relative water
      content froze at lower temperatures, and branch water content was lower in winter
      than in spring. A bench drying experiment with Picea abies confirmed that
      decreasing branch water potential decreases apoplastic ice nucleation
      temperature. The studied angiosperms froze on average 2.0 and 1.8 degrees C
      closer to zero Celsius than the studied gymnosperms during winter and spring,
      respectively. This was caused by higher relative water content in angiosperms;
      when branches were saturated with water, apoplastic ice nucleation temperature of
      gymnosperms increased to slightly higher temperature than that of angiosperms.
      Apoplastic ice nucleation temperature in sampled branches was positively
      correlated with xylem conduit diameter as shown before, but saturating the
      branches removed the correlation. Decrease in ice nucleation temperature
      decreased the duration of freezing, which could have an effect on winter embolism
      formation via the time available for gas escape during ice propagation. The
      apoplastic ice nucleation temperature varied not only between branches but also
      within a branch between consecutive freeze-thaw cycles demonstrating the
      stochastic nature of ice nucleation.

PMID- 29321876
TI  - Effects of social information on life history and mating tactics of males in the
      orb-web spider Argiope bruennichi.
AB  - Informed mating decisions are often based on social cues providing information
      about prospective mating opportunities. Social information early in life can
      trigger developmental modifications and influence later mating decisions. A high
      adaptive value of such adjustments is particularly obvious in systems where
      potential mating rates are extremely limited and have to be carried out in a
      short time window. Males of the sexually cannibalistic spider Argiope bruennichi
      can achieve maximally two copulations which they can use for one (monogyny) or
      two females (bigyny). The choice between these male mating tactics should rely on
      female availability that males might assess through volatile sex pheromones
      emitted by virgin females. We predict that in response to those female cues,
      males of A. bruennichi should mature earlier and at a smaller body size and favor
      a bigynous mating tactic in comparison with controls. We sampled spiders from two
      areas close to the Southern and Northern species range to account for differences
      in mate quality and seasonality. In a fully factorial design, half of the
      subadult males from both areas obtained silk cues of females, while the other
      half remained without female exposure. Adult males were subjected to no-choice
      mating tests and could either monopolize the female or leave her (bigyny). We
      found that Southern males matured later and at a larger size than Northern males.
      Regardless of their origin, males also shortened the subadult stage in response
      to female cues, which, however, had no effects on male body mass. Contrary to our
      prediction, the frequencies of mating tactics were unaffected by the treatment.
      We conclude that while social cues during late development elicit adaptive life
      history adjustments, they are less important for the adjustment of mating
      decisions. We suggest that male tactics mostly rely on local information at the
      time of mate search.

PMID- 29321877
TI  - Phenology largely explains taller grass at successful nests in greater sage
      grouse.
AB  - Much interest lies in the identification of manageable habitat variables that
      affect key vital rates for species of concern. For ground-nesting birds,
      vegetation surrounding the nest may play an important role in mediating nest
      success by providing concealment from predators. Height of grasses surrounding
      the nest is thought to be a driver of nest survival in greater sage-grouse
      (Centrocercus urophasianus; sage-grouse), a species that has experienced
      widespread population declines throughout their range. However, a growing body of
      the literature has found that widely used field methods can produce misleading
      inference on the relationship between grass height and nest success.
      Specifically, it has been demonstrated that measuring concealment following nest
      fate (failure or hatch) introduces a temporal bias whereby successful nests are
      measured later in the season, on average, than failed nests. This sampling bias
      can produce inference suggesting a positive effect of grass height on nest
      survival, though the relationship arises due to the confounding effect of plant
      phenology, not an effect on predation risk. To test the generality of this
      finding for sage-grouse, we reanalyzed existing datasets comprising >800 sage
      grouse nests from three independent studies across the range where there was a
      positive relationship found between grass height and nest survival, including two
      using methods now known to be biased. Correcting for phenology produced equivocal
      relationships between grass height and sage-grouse nest survival. Viewed in
      total, evidence for a ubiquitous biological effect of grass height on sage-grouse
      nest success across time and space is lacking. In light of these findings, a
      reevaluation of land management guidelines emphasizing specific grass height
      targets to promote nest success may be merited.

PMID- 29321878
TI  - Asymmetric reproductive interference: The consequences of cross-pollination on
      reproductive success in sexual-apomictic populations of Potentilla puberula
      (Rosaceae).
AB  - Apomixis evolves from a sexual background and usually is linked to
      polyploidization. Pseudogamous gametophytic apomicts, which require a
      fertilization to initiate seed development, of various ploidy levels frequently
      co-occur with their lower-ploid sexual ancestors, but the stability of such mixed
      populations is affected by reproductive interferences mediated by cross
      pollination. Thereby, reproductive success of crosses depends on the difference
      in ploidy levels of mating partners, that is, on tolerance of deviation from the
      balanced ratio of maternal versus paternal genomes. Quality of pollen can further
      affect reproductive success in intercytotype pollinations. Cross-fertilization,
      however, can be avoided by selfing which may be induced upon pollination with
      mixtures of self- and cross-pollen (i.e., mentor effects). We tested for
      reproductive compatibility of naturally co-occurring tetraploid sexuals and penta
      to octoploid apomicts in the rosaceous species Potentilla puberula by means of
      controlled crosses. We estimated the role of selfing as a crossing barrier and
      effects of self- and cross-pollen quality as well as maternal: paternal genomic
      ratios in the endosperm on reproductive success. Cross-fertilization of sexuals
      by apomicts was not blocked by selfing, and seed set was reduced in hetero-
      compared to homoploid crosses. Thereby, seed set was negatively related to
      deviations from balanced parental genomic ratios in the endosperm. In contrast,
      seed set in the apomictic cytotypes was not reduced in hetero- compared to
      homoploid crosses. Thus, apomictic cytotypes either avoided intercytotype cross
      fertilization through selfing, tolerated intercytotype cross-fertilizations
      without negative effects on reproductive success, or even benefitted from higher
      pollen quality in intercytotype pollinations. Our experiment provides evidence
      for asymmetric reproductive interference, in favor of the apomicts, with
      significantly reduced seed set of sexuals in cytologically mixed populations,
      whereas seed set in apomicts was not affected. Incompleteness of crossing
      barriers further indicated at least partial losses of a parental genomic
      endosperm balance requirement.

PMID- 29321879
TI  - Space-time clusters for early detection of grizzly bear predation.
AB  - Accurate detection and classification of predation events is important to
      determine predation and consumption rates by predators. However, obtaining this
      information for large predators is constrained by the speed at which carcasses
      disappear and the cost of field data collection. To accurately detect predation
      events, researchers have used GPS collar technology combined with targeted site
      visits. However, kill sites are often investigated well after the predation event
      due to limited data retrieval options on GPS collars (VHF or UHF downloading) and
      to ensure crew safety when working with large predators. This can lead to missing
      information from small-prey (including young ungulates) kill sites due to
      scavenging and general site deterioration (e.g., vegetation growth). We used a
      space-time permutation scan statistic (STPSS) clustering method (SaTScan) to
      detect predation events of grizzly bears (Ursus arctos) fitted with satellite
      transmitting GPS collars. We used generalized linear mixed models to verify
      predation events and the size of carcasses using spatiotemporal characteristics
      as predictors. STPSS uses a probability model to compare expected cluster size
      (space and time) with the observed size. We applied this method retrospectively
      to data from 2006 to 2007 to compare our method to random GPS site selection. In
      2013-2014, we applied our detection method to visit sites one week after their
      occupation. Both datasets were collected in the same study area. Our approach
      detected 23 of 27 predation sites verified by visiting 464 random grizzly bear
      locations in 2006-2007, 187 of which were within space-time clusters and 277
      outside. Predation site detection increased by 2.75 times (54 predation events of
      335 visited clusters) using 2013-2014 data. Our GLMMs showed that cluster size
      and duration predicted predation events and carcass size with high sensitivity
      (0.72 and 0.94, respectively). Coupling GPS satellite technology with clusters
      using a program based on space-time probability models allows for prompt visits
      to predation sites. This enables accurate identification of the carcass size and
      increases fieldwork efficiency in predation studies.

PMID- 29321880
TI  - Ocean acidification ameliorates harmful effects of warming in primary consumer.
AB  - Climate change-induced warming and ocean acidification are considered two
      imminent threats to marine biodiversity and current ecosystem structures. Here,
      we have for the first time examined an animal's response to a complete life cycle
      of exposure to co-occurring warming (+3 degrees C) and ocean acidification
      (+1,600 MUatm CO 2), using the key subarctic planktonic copepod, Calanus
      finmarchicus, as a model species. The animals were generally negatively affected
      by warming, which significantly reduced the females' energy status and
      reproductive parameters (respectively, 95% and 69%-87% vs. control).
      Unexpectedly, simultaneous acidification partially offset the negative effect of
      warming in an antagonistic manner, significantly improving reproductive
      parameters and hatching success (233%-340% improvement vs. single warming
      exposure). The results provide proof of concept that ocean acidification may
      partially offset negative effects caused by warming in some species. Possible
      explanations and ecological implications for the observed antagonistic effect are
      discussed.

PMID- 29321881
TI  - An approach based on the total-species accumulation curve and higher taxon
      richness to estimate realistic upper limits in regional species richness.
AB  - Most of accumulation curves tend to underestimate species richness, as they do
      not consider spatial heterogeneity in species distribution, or are structured to
      provide lower bound estimates and limited extrapolations. The total-species (T-S)
      curve allows extrapolations over large areas while taking into account spatial
      heterogeneity, making this estimator more prone to attempt upper bound estimates
      of regional species richness. However, the T-S curve may overestimate species
      richness due to (1) the mismatch among the spatial units used in the accumulation
      model and the actual units of variation in beta-diversity across the region, (2)
      small-scale patchiness, and/or (3) patterns of rarity of species. We propose a
      new framework allowing the T-S curve to limit overestimation and give an
      application to a large dataset of marine mollusks spanning over 11 km2 of
      subtidal bottom (W Mediterranean). As accumulation patterns are closely related
      across the taxonomic hierarchy up to family level, improvements of the T-S curve
      leading to more realistic estimates of family richness, that is, not exceeding
      the maximum number of known families potentially present in the area, can be
      considered as conducive to more realistic estimates of species richness. Results
      on real data showed that improvements of the T-S curve to accounts for true
      variations in beta-diversity within the sampled areas, small-scale patchiness,
      and rarity of families led to the most plausible richness when all aspects were
      considered in the model. Data on simulated communities indicated that in the
      presence of high heterogeneity, and when the proportion of rare species was not
      excessive (>2/3), the procedure led to almost unbiased estimates. Our findings
      highlighted the central role of variations in beta-diversity within the region
      when attempting to estimate species richness, providing a general framework
      exploiting the properties of the T-S curve and known family richness to estimate
      plausible upper bounds in gamma-diversity.

PMID- 29321882
TI  - Timescale effects on the environmental control of carbon and water fluxes of an
      apple orchard.
AB  - Model parameterization and validation of earth-atmosphere interactions are
      generally performed using a single timescale (e.g., nearly instantaneous, daily,
      and annual), although both delayed responses and hysteretic effects have been
      widely recognized. The lack of consideration of these effects hampers our
      capability to represent them in empirical- or process-based models. Here we
      explore, using an apple orchard ecosystem in the North of Italy as a simplified
      case study, how the considered timescale impacts the relative importance of the
      single environmental variables in explaining observed net ecosystem exchange
      (NEE) and evapotranspiration (ET). Using 6 years of eddy covariance and
      meteorological information as input data, we found a decay of the relative
      importance of the modeling capability of photosynthetically active radiation in
      explaining both NEE and ET moving from half-hourly to seasonal timescale and an
      increase in the relative importance of air temperature (T) and VPD. Satellite
      NDVI, used as proxy of leaf development, added little improvement to overall
      modeling capability. Increasing the timescale, the number of variables needed for
      parameterization decreased (from 5 to 1), while the proportion of variance
      explained by the model increased (r2 from 0.56-0.78 to 0.85-0.90 for NEE and ET
      respectively). The wavelet coherence and the phase analyses showed that the two
      variables that increased their relative importance when the scale increased (T,
      VPD) were not in phase at the correlation peak of both ET and NEE. This phase
      shift in the time domain corresponds to a hysteretic response in the
      meteorological variables domain. This work confirms that the model
      parameterization should be performed using parameters calculated at the
      appropriate scale. It suggests that in managed ecosystems, where the interannual
      variability is minimized by the agronomic practices, the use of timescales large
      enough to include hysteretic and delayed responses reduces the number of required
      input variables and improves their explanatory capacity.

PMID- 29321883
TI  - Quantifying the effects of ecological constraints on trait expression using novel
      trait-gradient analysis parameters.
AB  - Complex processes related to biotic and abiotic forces can impose limitations to
      assembly and composition of plant communities. Quantifying the effects of these
      constraints on plant functional traits across environmental gradients, and among
      communities, remains challenging. We define ecological constraint (Ci ) as the
      combined, limiting effect of biotic interactions and environmental filtering on
      trait expression (i.e., the mean value and range of functional traits). Here, we
      propose a set of novel parameters to quantify this constraint by extending the
      trait-gradient analysis (TGA) methodology. The key parameter is ecological
      constraint, which is dimensionless and can be measured at various scales, for
      example, on population and community levels. It facilitates comparing the effects
      of ecological constraints on trait expressions across environmental gradients, as
      well as within and among communities. We illustrate the implementation of the
      proposed parameters using the bark thickness of 14 woody species along an aridity
      gradient on granite outcrops in southwestern Australia. We found a positive
      correlation between increasing environmental stress and strength of ecological
      constraint on bark thickness expression. Also, plants from more stressful
      habitats (shrublands on shallow soils and in sun-exposed locations) displayed
      higher ecological constraint for bark thickness than plants in more benign
      habitats (woodlands on deep soils and in sheltered locations). The relative ease
      of calculation and dimensionless nature of Ci allow it to be readily implemented
      at various scales and make it widely applicable. It therefore has the potential
      to advance the mechanistic understanding of the ecological processes shaping
      trait expression. Some future applications of the new parameters could be
      investigating the patterns of ecological constraints (1) among communities from
      different regions, (2) on different traits across similar environmental
      gradients, and (3) for the same trait across different gradient types.

PMID- 29321885
TI  - Climate change affecting oil palm agronomy, and oil palm cultivation increasing
      climate change, require amelioration.
AB  - Palm oil is used in various valued commodities and is a large global industry
      worth over US$ 50 billion annually. Oil palms (OP) are grown commercially in
      Indonesia and Malaysia and other countries within Latin America and Africa. The
      large-scale land-use change has high ecological, economic, and social impacts.
      Tropical countries in particular are affected negatively by climate change (CC)
      which also has a detrimental impact on OP agronomy, whereas the cultivation of OP
      increases CC. Amelioration of both is required. The reduced ability to grow OP
      will reduce CC, which may allow more cultivation tending to increase CC, in a
      decreasing cycle. OP could be increasingly grown in more suitable regions
      occurring under CC. Enhancing the soil fauna may compensate for the effect of CC
      on OP agriculture to some extent. The effect of OP cultivation on CC may be
      reduced by employing reduced emissions from deforestation and forest degradation
      plans, for example, by avoiding illegal fire land clearing. Other ameliorating
      methods are reported herein. More research is required involving good management
      practices that can offset the increases in CC by OP plantations. Overall, OP
      growing countries should support the Paris convention on reducing CC as the most
      feasible scheme for reducing CC.

PMID- 29321884
TI  - Gut microbiota composition is associated with environmental landscape in honey
      bees.
AB  - There is growing recognition that the gut microbial community regulates a wide
      variety of important functions in its animal hosts, including host health.
      However, the complex interactions between gut microbes and environment are still
      unclear. Honey bees are ecologically and economically important pollinators that
      host a core gut microbial community that is thought to be constant across
      populations. Here, we examined whether the composition of the gut microbial
      community of honey bees is affected by the environmental landscape the bees are
      exposed to. We placed honey bee colonies reared under identical conditions in two
      main landscape types for 6 weeks: either oilseed rape farmland or agricultural
      farmland distant to fields of flowering oilseed rape. The gut bacterial
      communities of adult bees from the colonies were then characterized and compared
      based on amplicon sequencing of the 16S rRNA gene. While previous studies have
      delineated a characteristic core set of bacteria inhabiting the honey bee gut,
      our results suggest that the broad environment that bees are exposed to has some
      influence on the relative abundance of some members of that microbial community.
      This includes known dominant taxa thought to have functions in nutrition and
      health. Our results provide evidence for an influence of landscape exposure on
      honey bee microbial community and highlight the potential effect of exposure to
      different environmental parameters, such as forage type and neonicotinoid
      pesticides, on key honey bee gut bacteria. This work emphasizes the complexity of
      the relationship between the host, its gut bacteria, and the environment and
      identifies target microbial taxa for functional analyses.

PMID- 29321886
TI  - Gap formation and dynamics after long-term steady state in an old-growth Picea
      abies stand in Norway: Above- and belowground interactions.
AB  - Stand dynamics and the gap initiation prior to gap formation are not well
      understood because of its long-term nature and the scarcity of late-successional
      stands. Reconstruction of such disturbance is normally based on historical
      records and dendroecological methods. We investigated gap initiation and
      formation at the fine-scale stand level in the old-growth reserve of Karlshaugen
      in Norway. Given its long-term conservation history, and thorough mapping in
      permanent marked plots with spatially referenced trees, it provides an
      opportunity to present stand development before, during, and after gap formation.
      Late-successional decline in biomass was recorded after more than 50 years of
      close to steady state. Gaps in the canopy were mainly created by large old trees
      that had been killed by spruce bark beetles. Snapping by wind was the main reason
      for treefall. Long-term dominance of Norway spruce excluded downy birch and Scots
      pine from the stand. Comparisons of the forest floor soil properties between the
      gap and nongap area showed significantly higher concentrations of plant available
      Ca within the gap area. Plant root simulator (PRSTM) probes showed significantly
      higher supply rates for Ca and Mg, but significantly lower K for the gap compared
      to the nongap area. Soil water from the gap area had significantly higher C:N
      ratios compared to the nongap area. Fine-scale variation with increasing distance
      to logs indicated that CWD is important for leaking of DOC and Ca. Our long-term
      study from Karlshaugen documents gap dynamics after more than 50 years of steady
      state and a multiscale disturbance regime in an old-growth forest. The observed
      disturbance dynamic caused higher aboveground and belowground heterogeneity in
      plots, coarse woody debris, and nutrients. Our study of the nutrient levels of
      the forest floor suggest that natural gaps of old-growth forest provide a long
      lasting biogeochemical feedback system particularly with respect to Ca and
      probably also N. Norway spruce trees near the gap edge responded with high
      plasticity to reduced competition, showing the importance of the edge zone as hot
      spots for establishing heterogeneity, but also the potential for carbon
      sequestration in old-growth forest.

PMID- 29321887
TI  - Habitat formation prevails over predation in influencing fouling communities.
AB  - Coastal human-made structures, such as marinas and harbors, are expanding
      worldwide. Species assemblages described from these artificial habitats are novel
      relative to natural reefs, particularly in terms of the abundance of
      nonindigenous species (NIS). Although these fouling assemblages are clearly
      distinctive, the ecosystem functioning and species interactions taking place
      there are little understood. For instance, large predators may influence the
      fouling community development either directly (feeding on sessile fauna) or
      indirectly (feeding on small predators associated with these assemblages). In
      addition, by providing refuges, habitat complexity may modify the outcome of
      species interactions and the extent of biotic resistance (e.g., by increasing the
      abundance of niche-specific competitors and predators of NIS). Using experimental
      settlement panels deployed in the field for 2.5 months, we tested the influence
      of predation (i.e., caging experiment), artificial structural complexity (i.e.,
      mimics of turf-forming species), and their interactions (i.e., refuge effects) on
      the development of sessile and mobile fauna in two marinas. In addition, we
      tested the role of biotic complexity-arising from the habitat-forming species
      that grew on the panels during the trial-on the richness and abundance of mobile
      fauna. The effect of predation and artificial habitat complexity was negligible,
      regardless of assemblage status (i.e., native, cryptogenic, and nonindigenous).
      Conversely, habitat-forming species and associated epibionts, responsible for
      biotic complexity, had a significant effect on mobile invertebrates (richness,
      abundance, and community structure). In particular, the richness and abundance of
      mobile NIS were positively affected by biotic complexity, with site-dependent
      relationships. Altogether, our results indicate that biotic complexity prevails
      over artificial habitat complexity in determining the distribution of mobile
      species under low predation pressure. Facilitation of native and non-native
      species thus seems to act upon diversity and community development: This process
      deserves further consideration in models of biotic resistance to invasion in
      urban marine habitats.

PMID- 29321888
TI  - A general modeling framework for describing spatially structured population
      dynamics.
AB  - Variation in movement across time and space fundamentally shapes the abundance
      and distribution of populations. Although a variety of approaches model
      structured population dynamics, they are limited to specific types of spatially
      structured populations and lack a unifying framework. Here, we propose a unified
      network-based framework sufficiently novel in its flexibility to capture a wide
      variety of spatiotemporal processes including metapopulations and a range of
      migratory patterns. It can accommodate different kinds of age structures, forms
      of population growth, dispersal, nomadism and migration, and alternative life
      history strategies. Our objective was to link three general elements common to
      all spatially structured populations (space, time and movement) under a single
      mathematical framework. To do this, we adopt a network modeling approach. The
      spatial structure of a population is represented by a weighted and directed
      network. Each node and each edge has a set of attributes which vary through time.
      The dynamics of our network-based population is modeled with discrete time steps.
      Using both theoretical and real-world examples, we show how common elements recur
      across species with disparate movement strategies and how they can be combined
      under a unified mathematical framework. We illustrate how metapopulations,
      various migratory patterns, and nomadism can be represented with this modeling
      approach. We also apply our network-based framework to four organisms spanning a
      wide range of life histories, movement patterns, and carrying capacities. General
      computer code to implement our framework is provided, which can be applied to
      almost any spatially structured population. This framework contributes to our
      theoretical understanding of population dynamics and has practical management
      applications, including understanding the impact of perturbations on population
      size, distribution, and movement patterns. By working within a common framework,
      there is less chance that comparative analyses are colored by model details
      rather than general principles.

PMID- 29321889
TI  - Using expert knowledge to incorporate uncertainty in cause-of-death assignments
      for modeling of cause-specific mortality.
AB  - Implicit and explicit use of expert knowledge to inform ecological analyses is
      becoming increasingly common because it often represents the sole source of
      information in many circumstances. Thus, there is a need to develop statistical
      methods that explicitly incorporate expert knowledge, and can successfully
      leverage this information while properly accounting for associated uncertainty
      during analysis. Studies of cause-specific mortality provide an example of
      implicit use of expert knowledge when causes-of-death are uncertain and assigned
      based on the observer's knowledge of the most likely cause. To explicitly
      incorporate this use of expert knowledge and the associated uncertainty, we
      developed a statistical model for estimating cause-specific mortality using a
      data augmentation approach within a Bayesian hierarchical framework.
      Specifically, for each mortality event, we elicited the observer's belief of
      cause-of-death by having them specify the probability that the death was due to
      each potential cause. These probabilities were then used as prior predictive
      values within our framework. This hierarchical framework permitted a simple and
      rigorous estimation method that was easily modified to include covariate effects
      and regularizing terms. Although applied to survival analysis, this method can be
      extended to any event-time analysis with multiple event types, for which there is
      uncertainty regarding the true outcome. We conducted simulations to determine how
      our framework compared to traditional approaches that use expert knowledge
      implicitly and assume that cause-of-death is specified accurately. Simulation
      results supported the inclusion of observer uncertainty in cause-of-death
      assignment in modeling of cause-specific mortality to improve model performance
      and inference. Finally, we applied the statistical model we developed and a
      traditional method to cause-specific survival data for white-tailed deer, and
      compared results. We demonstrate that model selection results changed between the
      two approaches, and incorporating observer knowledge in cause-of-death increased
      the variability associated with parameter estimates when compared to the
      traditional approach. These differences between the two approaches can impact
      reported results, and therefore, it is critical to explicitly incorporate expert
      knowledge in statistical methods to ensure rigorous inference.

PMID- 29321890
TI  - Nature versus nurture? Consequences of short captivity in early stages.
AB  - Biological changes occurring as a consequence of domestication and/or captivity
      are not still deeply known. In Atlantic salmon (Salmo salar), endangered
      (Southern Europe) populations are enhanced by supportive breeding, which involves
      only 6 months of captive rearing following artificial spawning of wild-collected
      adults. In this work, we assess whether several fitness-correlated life-history
      traits (migratory behavior, straying rate, age at maturity, and growth) are
      affected by early exposure to the captive environment within a generation, before
      reproduction thus before genetic selection. Results showed significant
      differences in growth and migratory behavior (including straying), associated
      with this very short period of captivity in natural fish populations, changing
      even genetic variability (decreased in hatchery-reared adults) and the native
      population structure within and between rivers of the species. These changes
      appeared within a single generation, suggesting very short time of captivity is
      enough for initiating changes normally attributed to domestication. These results
      may have potential implications for the long-term population stability/viability
      of species subjected to restoration and enhancement processes and could be also
      considered for the management of zoo populations.

PMID- 29321892
TI  - Regional patterns of declining butternut (Juglans cinerea L.) suggest site
      characteristics for restoration.
AB  - Butternut trees dying from a canker disease were first reported in southwestern
      Wisconsin in 1967. Since then, the disease has caused extensive mortality of
      butternut throughout its North American range. The objectives of this study were
      to quantify changes in butternut populations and density across its range and
      identify habitat characteristics of sites where butternut is surviving in order
      to locate regions for potential butternut restoration. The natural range of
      butternut (Juglans cinerea L.) extends over a large region of eastern N. America
      encompassing New Brunswick south to North Carolina, north to Minnesota, and
      southwest to Missouri. Despite the species' large range, it is typically not a
      common tree, comprising a relatively minor component of several different forest
      types. We evaluated change in butternut abundance and volume from current and
      historic data from 21 states in the eastern United States. We related abundance
      and volume at two time periods to a suite of ecological and site factors in order
      to characterize site conditions where butternut survived. We also assessed the
      current level of butternut mortality across its range. Since the 1980s, the
      number of butternut trees and butternut volume have decreased by 58% and 44%,
      respectively, across its US range. Substantial relative decreases in tree numbers
      and volume occurred in most ecoregion sections. Five environmental variables were
      found to be significant predictors of butternut presence. The potential impacts
      of butternut canker are particularly acute as the canker pathogen invasion pushes
      a rare tree species toward extinction, at least at a local scale. Based on the
      results presented here, large-diameter maple/beech/birch stands in dry, upland
      sites in eastern Minnesota, western Wisconsin, and upstate New York appear to
      offer the most favorable conditions for butternut growth and survival and thus
      may be the best stands for planting resistant butternut trees.

PMID- 29321891
TI  - Population genetic structure of the endemic rosewoods Dalbergia cochinchinensis
      and D. oliveri at a regional scale reflects the Indochinese landscape and life
      history traits.
AB  - Indochina is a biodiversity hot spot and harbors a high number of endemic
      species, most of which are poorly studied. This study explores the genetic
      structure and reproductive system of the threatened endemic timber species
      Dalbergia cochinchinensis and Dalbergia oliveri using microsatellite data from
      populations across Indochina and relates it to landscape characteristics and life
      history traits. We found that the major water bodies in the region, Mekong and
      Tonle Sap, represented barriers to gene flow and that higher levels of genetic
      diversity were found in populations in the center of the distribution area,
      particularly in Cambodia. We suggest that this pattern is ancient, reflecting the
      demographic history of the species and possible location of refugia during
      earlier time periods with limited forest cover, which was supported by signs of
      old genetic bottlenecks. The D. oliveri populations had generally high levels of
      genetic diversity (mean He = 0.73), but also strong genetic differentiation among
      populations (global GST = 0.13), while D. cochinchinensis had a moderate level of
      genetic diversity (mean He = 0.55), and an even stronger level of differentiation
      (global GST = 0.25). These differences in genetic structure can be accounted for
      by a higher level of gene flow in D. oliveri due to a higher dispersal capacity,
      but also by the broader distribution area for D. oliveri, and the pioneer
      characteristics of D. cochinchinensis. This study represents the first detailed
      analysis of landscape genetics for tree species in Indochina, and the found
      patterns might be common for other species with similar ecology.

PMID- 29321893
TI  - Opposing deer and caterpillar foraging preferences may prevent reductions in
      songbird prey biomass in historically overbrowsed forests.
AB  - Overbrowsing by ungulates decimates plant populations and reduces diversity in a
      variety of ecosystems, but the mechanisms by which changes to plant community
      composition influence other trophic levels are poorly understood. In addition to
      removal of avian nesting habitat, browsing is hypothesized to reduce bird density
      and diversity through reduction of insect prey on browse-tolerant hosts left
      behind by deer. In this study, we excluded birds from branches of six tree
      species to quantify differences in songbird prey removal across trees that vary
      in deer browse preference. Early in the breeding season, birds preyed on
      caterpillars at levels proportional to their abundance on each host. Combining
      these data with tree species composition data from stands exposed to
      experimentally controlled deer densities over 30 years ago, we tested whether
      overbrowsing by white-tailed deer reduces prey biomass long after deer densities
      are reduced. Our analysis predicts total prey availability in the canopy of
      regenerating forests is fairly robust to historic exposure to high deer
      densities, though distribution of prey available from host species changes
      dramatically. This predicted compensatory effect was unexpected and is driven by
      high prey abundance on a single host tree species avoided by browsing deer,
      Prunus serotina. Thus, while we confirm that prey abundance on host trees can act
      as a reliable predictor for relative prey availability, this study shows that
      quantifying prey abundance across host trees is essential to understanding how
      changes in tree species composition interact with ungulate browse preference to
      determine prey availability for songbirds.

PMID- 29321895
TI  - Impact of male alternative reproductive tactics on female costs of sexual
      conflict under variation in operational sex ratio and population density.
AB  - Sexual conflict over mating rate is both pervasive and evolutionarily costly. For
      females, the lifetime reproductive fitness costs that arise through interactions
      with potential mates will be influenced by the frequency of such interactions,
      and the fitness cost of each interaction. Both of these factors are likely to be
      influenced by variation in operational sex ratio (OSR) and population density.
      Variation in OSR- and density-dependent male alternative reproductive tactics
      (ARTs) may be particularly important if the fitness costs that females experience
      vary with the reproductive tactics that males express. Using a simple model, we
      consider several examples of OSR- and/or density-dependent variation in male ARTs
      and the frequency of male-female interactions, and find that variation in the
      expression of male ARTs has the potential to augment or diminish the costs of
      frequent male interactions for females. Accurately documenting variation in the
      expression of male ARTs and associated female fitness costs will benefit future
      work in this area.

PMID- 29321894
TI  - Development of a genotype-by-sequencing immunogenetic assay as exemplified by
      screening for variation in red fox with and without endemic rabies exposure.
AB  - Pathogens are recognized as major drivers of local adaptation in wildlife
      systems. By determining which gene variants are favored in local interactions
      among populations with and without disease, spatially explicit adaptive responses
      to pathogens can be elucidated. Much of our current understanding of host
      responses to disease comes from a small number of genes associated with an immune
      response. High-throughput sequencing (HTS) technologies, such as genotype-by
      sequencing (GBS), facilitate expanded explorations of genomic variation among
      populations. Hybridization-based GBS techniques can be leveraged in systems not
      well characterized for specific variants associated with disease outcome to
      "capture" specific genes and regulatory regions known to influence expression and
      disease outcome. We developed a multiplexed, sequence capture assay for red foxes
      to simultaneously assess ~300-kbp of genomic sequence from 116 adaptive,
      intrinsic, and innate immunity genes of predicted adaptive significance and their
      putative upstream regulatory regions along with 23 neutral microsatellite regions
      to control for demographic effects. The assay was applied to 45 fox DNA samples
      from Alaska, where three arctic rabies strains are geographically restricted and
      endemic to coastal tundra regions, yet absent from the boreal interior. The assay
      provided 61.5% on-target enrichment with relatively even sequence coverage across
      all targeted loci and samples (mean = 50*), which allowed us to elucidate genetic
      variation across introns, exons, and potential regulatory regions (4,819 SNPs).
      Challenges remained in accurately describing microsatellite variation using this
      technique; however, longer-read HTS technologies should overcome these issues. We
      used these data to conduct preliminary analyses and detected genetic structure in
      a subset of red fox immune-related genes between regions with and without endemic
      arctic rabies. This assay provides a template to assess immunogenetic variation
      in wildlife disease systems.

PMID- 29321896
TI  - How much of the invader's genetic variability can slip between our fingers? A
      case study of secondary dispersal of Poa annua on King George Island
      (Antarctica).
AB  - We studied an invasion of Poa annua on King George Island (Maritime Antarctic).
      The remoteness of this location, its geographic isolation, and its limited human
      traffic provided an opportunity to trace the history of an invasion of the
      species. Poa annua was recorded for the first time at H. Arctowski Polish
      Antarctic Station in the austral summer of 1985/6. In 2008/9, the species was
      observed in a new locality at the Ecology Glacier Forefield (1.5 km from
      "Arctowski"). We used AFLP to analyze the genetic differences among three
      populations of P. annua: the two mentioned above (Station and Forefield) and the
      putative origin of the introduction, Warsaw (Poland). There was 38% genetic
      variance among the populations. Pairwise FPT was 0.498 between the Forefield and
      Warsaw populations and 0.283 between Warsaw and Station. There were 15 unique
      bands in the Warsaw population (frequency from 6% to 100%) and one in the
      Station/Forefield populations (which appears in all analyzed individuals from
      both populations). The Delta(K) parameter indicated two groups of samples:
      Warsaw/Station and Forefield. As indicated by Fu's Fs statistics and an analysis
      of mismatch distribution, the Forefield population underwent a bottleneck and/or
      founder effect. The Forefield population was likely introduced by secondary
      dispersal from the Station population.

PMID- 29321897
TI  - Nutrient stoichiometry and land use rather than species richness determine plant
      functional diversity.
AB  - Plant functional traits reflect individual and community ecological strategies.
      They allow the detection of directional changes in community dynamics and
      ecosystemic processes, being an additional tool to assess biodiversity than
      species richness. Analysis of functional patterns in plant communities provides
      mechanistic insight into biodiversity alterations due to anthropogenic activity.
      Although studies have consi-dered of either anthropogenic management or nutrient
      availability on functional traits in temperate grasslands, studies combining
      effects of both drivers are scarce. Here, we assessed the impacts of management
      intensity (fertilization, mowing, grazing), nutrient stoichiometry (C, N, P, K),
      and vegetation composition on community-weighted means (CWMs) and functional
      diversity (Rao's Q) from seven plant traits in 150 grasslands in three regions in
      Germany, using data of 6 years. Land use and nutrient stoichiometry accounted for
      larger proportions of model variance of CWM and Rao's Q than species richness and
      productivity. Grazing affected all analyzed trait groups; fertilization and
      mowing only impacted generative traits. Grazing was clearly associated with
      nutrient retention strategies, that is, investing in durable structures and
      production of fewer, less variable seed. Phenological variability was increased.
      Fertilization and mowing decreased seed number/mass variability, indicating
      competition-related effects. Impacts of nutrient stoichiometry on trait syndromes
      varied. Nutrient limitation (large N:P, C:N ratios) promoted species with
      conservative strategies, that is, investment in durable plant structures rather
      than fast growth, fewer seed, and delayed flowering onset. In contrast to seed
      mass, leaf-economics variability was reduced under P shortage. Species diversity
      was positively associated with the variability of generative traits. Synthesis.
      Here, land use, nutrient availability, species richness, and plant functional
      strategies have been shown to interact complexly, driving community composition,
      and vegetation responses to management intensity. We suggest that deeper
      understanding of underlying mechanisms shaping community assembly and
      biodiversity will require analyzing all these parameters.

PMID- 29321898
TI  - Sap flow characteristics and responses to summer rainfall for Pinus tabulaeformis
      and Hippophae rhamnoides in the Loess hilly region of China.
AB  - As a major driving element of the structure and function of arid and semiarid
      ecosystems, rainfall is the essential factor limiting plant biological processes.
      To clarify the characteristics of transpiration and responses to summer rainfall,
      sap flow density (Fd) of Pinus tabulaeformis and Hippophae rhamnoides was
      monitored using thermal dissipation probes. In addition, midday leaf water
      potential (psim) and leaf stomatal conductance (Gs) were also analyzed to
      determine water use strategies. The results indicated that the diurnal variation
      in the normalized Fd values exhibited a single-peak curve for P. tabulaeformis,
      while H. rhamnoides showed multiple peaks. The normalized Fd for P. tabulaeformis
      remained relatively stable regardless of rainfall events. However, there was also
      a significant increase in the normalized Fd for H. rhamnoides in response to
      rainfall in June and August (p < .05), although no significant differences were
      observed in July. The normalized Fd values for P. tabulaeformis and H. rhamnoides
      fitted well with the derived variable of transpiration, an integrated index
      calculated from the vapor pressure deficit and solar radiation (Rs), using an
      exponential saturation function. The differences in fitting coefficients
      suggested that H. rhamnoides showed more sensitivity to summer rainfall (p < .01)
      than P. tabulaeformis. Furthermore, during the study period, P. tabulaeformis
      reduced Gs as soil water decreased, maintaining a relatively constant psim; while
      H. rhamnoides allowed large fluctuations in psim to maintain Gs. Therefore, P.
      tabulaeformis and H. rhamnoides should be considered isohydric and anisohydric
      species, respectively. And more consideration should be taken for H. rhamnoides
      in the afforestation activities and the local plantation management under the
      context of the frequently seasonal drought in the loess hilly region.

PMID- 29321899
TI  - Silicon amendment to rice plants contributes to reduced feeding in a phloem
      sucking insect through modulation of callose deposition.
AB  - Silicon (Si) uptake by Poaceae plants has beneficial effects on herbivore
      defense. Increased plant physical barrier and altered herbivorous feeding
      behaviors are documented to reduce herbivorous arthropod feeding and contribute
      to enhanced plant defense. Here, we show that Si amendment to rice (Oryza sativa)
      plants contributes to reduced feeding in a phloem feeder, the brown planthopper
      (Nilaparvata lugens, BPH), through modulation of callose deposition. We
      associated the temporal dynamics of BPH feeding with callose deposition on sieve
      plates and further with callose synthase and hydrolase gene expression in plants
      amended with Si. Biological assays revealed that BPH feeding was lower in Si
      amended than in nonamended plants in the early stages post-BPH infestation.
      Histological observation showed that BPH infestation triggered fast and strong
      callose deposition in Si-amended plants compared with nonamended plants. Analysis
      using qRT-PCR revealed that expression of the callose synthase gene OsGSL1 was up
      regulated more and that the callose hydrolase (beta-1,3-glucanase) gene Gns5 was
      up-regulated less in Si-amended than in nonamended plants during the initial
      stages of BPH infestation. These dynamic expression levels of OsGSL1 and Gns5 in
      response to BPH infestation correspond to callose deposition patterns in Si
      amended versus nonamended plants. It is demonstrated here that BPH infestation
      triggers differential gene expression associated with callose synthesis and
      hydrolysis in Si-amended and nonamended rice plants, which allows callose to be
      deposited more on sieve tubes and sieve tube occlusions to be maintained more
      thus contributing to reduced BPH feeding on Si-amended plants.

PMID- 29321900
TI  - Changing methodology results in operational drift in the meaning of leaf area
      index, necessitating implementation of foliage layer index.
AB  - Leaf area index (LAI) was developed to describe the number of layers of foliage
      in a monoculture. Subsequent expansion into measurement by remote-sensing methods
      has resulted in misrepresentation of LAI. The new name foliage layer index (FLI)
      is applied to a more simply estimated version of Goodall's "cover repetition,"
      that is, the number of layers of foliage a single species has, either within a
      community or in monoculture. The relationship of FLI with cover is demonstrated
      in model communities, and some potential relationships between FLI and species'
      habit are suggested. FLI comm is a new formulation for the number of layers of
      foliage in a mixed-species' community. LAI should now be reserved for remote
      sensing applications in mixed communities, where it is probably a nonlinear
      measure of the density of light-absorbing pigments.

PMID- 29321901
TI  - Proximate causes of altitudinal differences in body size in an agamid lizard.
AB  - Body size is directly linked to key life history traits such as growth,
      fecundity, and survivorship. Identifying the causes of body size variation is a
      critical task in ecological and evolutionary research. Body size variation along
      altitudinal gradients has received considerable attention; however, the
      underlying mechanisms are poorly understood. Here, we compared the growth rate
      and age structure of toad-headed lizards (Phrynocephalus vlangalii) from two
      populations found at different elevations in the Qinghai-Tibetan Plateau. We used
      mark-recapture and skeletochronological analysis to identify the potential
      proximate causes of altitudinal variation in body size. Lizards from the high
      elevation site had higher growth rates and attained slightly larger adult body
      sizes than lizards from the low-elevation site. However, newborns produced by
      high-elevation females were smaller than those by low-elevation females. Von
      Bertalanffy growth estimates predicted high-elevation individuals would reach
      sexual maturity at an earlier age and have a lower mean age than low-elevation
      individuals. Relatively lower mean age for the high-elevation population was
      confirmed using the skeletochronological analysis. These results support the
      prediction that a larger adult body size of high-elevation P. vlangalii results
      from higher growth rates, associated with higher resource availability.

PMID- 29321902
TI  - Early phenology and growth trait variation in closely related European pine
      species.
AB  - Closely related taxa occupying different environments are valuable systems for
      studying evolution. In this study, we examined differences in early phenology
      (bud set, bud burst) and early growth in a common garden trial of closely related
      pine species: Pinus sylvestris, P. mugo, and P. uncinata. Seeds for the trial
      were sourced from populations across the ranges of each species in Europe. Over
      first 4 years of development, clear differences were observed between species,
      while the most significant intraspecific differentiation was observed among
      plants from P. sylvestris populations from continental European locations. Trait
      differences within P. sylvestris were highly correlated with altitude and
      latitude of the site of origin. Meanwhile, P. mugo populations from the
      Carpathians had the earliest bud set and bud flush compared to other populations
      of the species. Overall, populations from the P. mugo complex from heterogeneous
      mountain environments and P. sylvestris from the Scottish Highlands showed the
      highest within-population variation for the focal traits. Although the three
      species have been shown to be genetically highly similar, this study reveals
      large differences in key adaptive traits both among and within species.

PMID- 29321903
TI  - Separating the effects of water quality and urbanization on temperate
      insectivorous bats at the landscape scale.
AB  - Many local scale studies have shown that bats respond to water quality
      degradation or urbanization in a species-specific manner. However, few have
      separated the effects of urbanization versus water quality degradation on bats,
      in single city or single watershed case studies. Across North Carolina, USA, we
      used the standardized North American Bat Monitoring Program mobile transect
      protocol to survey bat activity in 2015 and 2016 at 41 sites. We collected
      statewide water quality and urban land cover data to disentangle the effects of
      urbanization and water quality degradation on bats at the landscape scale. We
      found that statewide, water quality degradation and urbanization were not
      correlated. We found that bats responded to water quality degradation and
      urbanization independently at the landscape scale. Eptesicus fuscus and Lasiurus
      cinereus negatively responded to water quality degradation. Lasiurus borealis and
      Perimyotis subflavus positively responded to water quality degradation.
      Lasionycteris noctivagans did not respond to water quality degradation but was
      more active in more urbanized areas. Tadarida brasiliensis positively responded
      to urbanization and was less active in areas with degraded water quality. We show
      that bat-water quality relationships found at the local scale are evident at a
      landscape scale. We confirm that bats are useful bioindicators for both
      urbanization and water quality degradation. We suggest that water quality can be
      used to predict the presence of bat species of conservation concern, such as P.
      subflavus, in areas where it has not been studied locally.

PMID- 29321904
TI  - Offspring of older parents are smaller-but no less bilaterally symmetrical-than
      offspring of younger parents in the aquatic plant Lemna turionifera.
AB  - Offspring quality decreases with parental age in many taxa, with offspring of
      older parents exhibiting reduced life span, reproductive capacity, and fitness,
      compared to offspring of younger parents. These "parental age effects," whose
      consequences arise in the next generation, can be considered as manifestations of
      parental senescence, in addition to the more familiar age-related declines in
      parent-generation survival and reproduction. Parental age effects are important
      because they may have feedback effects on the evolution of demographic
      trajectories and longevity. In addition to altering the timing of offspring life
      history milestones, parental age effects can also have a negative impact on
      offspring size, with offspring of older parents being smaller than offspring of
      younger parents. Here, we consider the effects of advancing parental age on a
      different aspect of offspring morphology, body symmetry. In this study, we
      followed all 403 offspring of 30 parents of a bilaterally symmetrical, clonally
      reproducing aquatic plant species, Lemna turionifera, to test the hypothesis that
      successive offspring become less symmetrical as their parent ages, using the
      "Continuous Symmetry Measure" as an index. Although successive offspring of aging
      parents older than one week became smaller and smaller, we found scant evidence
      for any reduction in bilateral symmetry.

PMID- 29321905
TI  - Detection and persistence of environmental DNA from an invasive, terrestrial
      mammal.
AB  - Invasive Sus scrofa, a species commonly referred to as wild pig or feral swine,
      is a destructive invasive species with a rapidly expanding distribution across
      the United States. We used artificial wallows and small waterers to determine the
      minimum amount of time needed for pig eDNA to accumulate in the water source to a
      detectable level. We removed water from the artificial wallows and tested eDNA
      detection over the course of 2 weeks to understand eDNA persistence. We show that
      our method is sensitive enough to detect very low quantities of eDNA shed by a
      terrestrial mammal that has limited interaction with water. Our experiments
      suggest that the number of individuals shedding into a water system can affect
      persistence of eDNA. Use of an eDNA detection technique can benefit management
      efforts by providing a sensitive method for finding even small numbers of
      individuals that may be elusive using other methods.

PMID- 29321906
TI  - Advancing breeding phenology does not affect incubation schedules in chestnut
      crowned babblers: Opposing effects of temperature and wind.
AB  - Projecting population responses to climate change requires an understanding of
      climatic impacts on key components of reproduction. Here, we investigate the
      associations among breeding phenology, climate and incubation schedules in the
      chestnut-crowned babbler (Pomatostomus ruficeps), a 50 g passerine with female
      only, intermittent incubation that typically breeds from late winter (July) to
      early summer (November). During daylight hours, breeding females spent an average
      of 33 min on the nest incubating (hereafter on-bouts) followed by 24-min foraging
      (hereafter off-bouts), leading to an average daytime nest attentiveness of 60%.
      Nest attentiveness was 25% shorter than expected from allometric calculations,
      largely because off-bout durations were double the expected value for a species
      with 16 g clutches (4 eggs * 4 g/egg). On-bout durations and daily attentiveness
      were both negatively related to ambient temperature, presumably because
      increasing temperatures allowed more time to be allocated to foraging with
      reduced detriment to egg cooling. By contrast, on-bout durations were positively
      associated with wind speed, in this case because increasing wind speed
      exacerbated egg cooling during off-bouts. Despite an average temperature change
      of 12 degrees C across the breeding season, breeding phenology had no effect on
      incubation schedules. This surprising result arose because of a positive
      relationship between temperature and wind speed across the breeding season: Any
      benefit of increasing temperatures was canceled by apparently detrimental
      consequences of increasing wind speed on egg cooling. Our results indicate that a
      greater appreciation for the associations among climatic variables and their
      independent effects on reproductive investment are necessary to understand the
      effects of changing climates on breeding phenology.

PMID- 29321907
TI  - The Groot Effect: Plant facilitation and desert shrub regrowth following
      extensive damage.
AB  - Deserts are increasing in extent globally, but existing deserts are decreasing in
      health. The basic biology and ecology of foundation plant species in deserts are
      limited. This is a direct study that provides an estimate of the capacity for a
      locally dominant foundation shrub species in California to recover from damage.
      Desert shrubs are cleared and damaged by humans for many purposes including
      agriculture, oil and gas production, and sustainable energy developments; we need
      to know whether foundation species consistently facilitate the abundance and
      diversity of other plants in high-stress ecosystems and whether they can recover.
      A total of 20 Ephedra californica shrubs were clipped to the ground at a single
      site and systematically resampled for regrowth 2 years later. These shrubs were
      damaged once and regrew rapidly, and relatively, larger shrubs were not more
      resilient. This study provides evidence for what we termed the "Groot Effect"
      because smaller individuals of this shrub species can recover from significant
      aboveground damage and continue to have positive effects on other plant species
      (similar to the popular culture reference to a benefactor tree species). The
      density of other plant species was consistently facilitated while effects on
      diversity varied with season. These findings confirm that E. californica is a
      foundation species that can be an important restoration tool within the deserts
      of California in spite of extreme cycles of drought and physical damage to its
      canopy.

PMID- 29321908
TI  - Rapid song divergence leads to discordance between genetic distance and
      phenotypic characters important in reproductive isolation.
AB  - The criteria for species delimitation in birds have long been debated, and
      several recent studies have proposed new methods for such delimitation. On one
      side, there is a large consensus of investigators who believe that the only
      evidence that can be used to delimit species is molecular phylogenetics, and with
      increasing numbers of markers to gain better support, whereas on the other, there
      are investigators adopting alternative approaches based largely on phenotypic
      differences, including in morphology and communication signals. Yet, these
      methods have little to say about rapid differentiation in specific traits shown
      to be important in reproductive isolation. Here, we examine variation in
      phenotypic (morphology, plumage, and song) and genotypic (mitochondrial and
      nuclear DNA) traits among populations of yellow-rumped tinkerbird Pogoniulus
      bilineatus in East Africa. Strikingly, song divergence between the P. b. fischeri
      subspecies from Kenya and Zanzibar and P. b. bilineatus from Tanzania is
      discordant with genetic distance, having occurred over a short time frame, and
      playback experiments show that adjacent populations of P. b. bilineatus and P. b.
      fischeri do not recognize one another's songs. While such rapid divergence might
      suggest a founder effect following invasion of Zanzibar, molecular evidence
      suggests otherwise, with insular P. b. fischeri nested within mainland P. b.
      fischeri. Populations from the Eastern Arc Mountains are genetically more
      distant, yet share the same song with P. b. bilineatus from Coastal Tanzania and
      Southern Africa, suggesting they would interbreed. We believe investigators ought
      to examine potentially rapid divergence in traits important in species
      recognition and sexual selection when delimiting species, rather than relying
      entirely on arbitrary quantitative characters or molecular markers.

PMID- 29321909
TI  - Detecting rare carnivores using scats: Implications for monitoring a fox
      incursion into Tasmania.
AB  - The ability to detect the incursion of an invasive species or destroy the last
      individuals during an eradication program are some of the most difficult aspects
      of invasive species management. The presence of foxes in Tasmania is a
      contentious issue with recent structured monitoring efforts, involving collection
      of carnivore scats and testing for fox DNA, failing to detect any evidence of
      foxes. Understanding the likelihood that monitoring efforts would detect fox
      presence, given at least one is present, is therefore critical for understanding
      the role of scat monitoring for informing the response to an incursion. We
      undertook trials to estimate the probability of fox scat detection through
      monitoring by scat-detector dogs and person searches and used this information to
      critically evaluate the power of scat monitoring efforts for detecting foxes in
      the Tasmanian landscape. The probability of detecting a single scat present in a
      1-km2 survey unit was highest for scat-detector dogs searches (0.053) compared
      with person searches (x-?0.015) for each 10 km of search effort. Simulation of
      the power of recent scat monitoring efforts undertaken in Tasmania from 2011 to
      2015 suggested that single foxes would have to be present in at least 20
      different locations or fox breeding groups present in at least six different
      locations, in order to be detected with a high level of confidence (>0.80). We
      have shown that highly structured detection trials can provide managers with the
      quantitative tools needed to make judgments about the power of large-scale scat
      monitoring programs. Results suggest that a fox population, if present in
      Tasmania, could remain undetected by a large-scale, structured scat monitoring
      program. Therefore, it is likely that other forms of surveillance, in conjunction
      with scat monitoring, will be necessary to demonstrate that foxes are absent from
      Tasmania with high confidence.

PMID- 29321910
TI  - Why does oriental arborvitae grow better when mixed with black locust: Insight on
      nutrient cycling?
AB  - To identify why tree growth differs by afforestation type is a matter of prime
      concern in forestry. A study was conducted to determine why oriental arborvitae
      (Platycladus orientalis) grows better in the presence of black locust (Robinia
      pseudoacacia) than in monoculture. Different types of stands (i.e., monocultures
      and mixture of black locust and oriental arborvitae, and native grassland as a
      control) were selected in the Loess Plateau, China. The height and diameter at
      breast height of each tree species were measured, and soil, shoot, and root
      samples were sampled. The arbuscular mycorrhizal (AM) attributes, shoot and root
      nutrient status, height and diameter of black locust were not influenced by the
      presence of oriental arborvitae. For oriental arborvitae, however, growing in
      mixture increased height and diameter and reduced shoot Mn, Ca, and Mg contents,
      AM fungal spore density, and colonization rate. Major changes in soil properties
      also occurred, primarily in soil water, NO 3-N, and available K levels and in
      soil enzyme activity. The increase in soil water, N, and K availability in the
      presence of black locust stimulated oriental arborvitae growth, and black locust
      in the mixed stand seems to suppress the development of AM symbiosis in oriental
      arborvitae roots, especially the production of AM fungal spores and vesicles,
      through improving soil water and N levels, thus freeing up carbon to fuel plant
      growth. Overall, the presence of black locust favored oriental arborvitae growth
      directly by improving soil water and fertility and indirectly by repressing AM
      symbiosis in oriental arborvitae roots.

PMID- 29321911
TI  - Low genetic variation of invasive Fallopia spp. in their northernmost European
      distribution range.
AB  - Knowledge about the reproduction strategies of invasive species is fundamental
      for effective control. The invasive Fallopia taxa (Japanese knotweed s.l.)
      reproduce mainly clonally in Europe, and preventing spread of vegetative
      fragments is the most important control measure. However, high levels of genetic
      variation within the hybrid F. * bohemica indicate that hybridization and seed
      dispersal could be important. In Norway in northern Europe, it is assumed that
      these taxa do not reproduce sexually due to low temperatures in the autumn when
      the plants are flowering. The main objective of this study was to examine the
      genetic variation of invasive Fallopia taxa in selected areas in Norway in order
      to evaluate whether the taxa may reproduce by seeds in their most northerly
      distribution range in Europe. Fallopia stands from different localities in Norway
      were analyzed with respect to prevalence of taxa, and genetic variation within
      and between taxa was studied using amplified fragment length polymorphism (AFLP).
      Taxonomic identification based on morphology corresponded with identification
      based on simple sequence repeats (SSR) and DNA ploidy levels (8* F. japonica, 6*
      F. * bohemica and 4* F. sachalinensis). No genetic variation within F. japonica
      was detected. All F. * bohemica samples belonged to a single AFLP genotype, but
      one sample had a different SSR genotype. Two SSR genotypes of F. sachalinensis
      were also detected. Extremely low genetic variation within the invasive Fallopia
      taxa indicates that these taxa do not reproduce sexually in the region,
      suggesting that control efforts can be focused on preventing clonal spread.
      Climate warming may increase sexual reproduction of invasive Fallopia taxa in
      northern regions. The hermaphrodite F. * bohemica is a potential pollen source
      for the male-sterile parental species. Targeted eradication of the hybrid can
      therefore reduce the risk of increased sexual reproduction under future warmer
      climate.

PMID- 29321912
TI  - Why georeferencing matters: Introducing a practical protocol to prepare species
      occurrence records for spatial analysis.
AB  - Species Distribution Models (SDMs) are widely used to understand environmental
      controls on species' ranges and to forecast species range shifts in response to
      climatic changes. The quality of input data is crucial determinant of the model's
      accuracy. While museum records can be useful sources of presence data for many
      species, they do not always include accurate geographic coordinates. Therefore,
      actual locations must be verified through the process of georeferencing. We
      present a practical, standardized manual georeferencing method (the Spatial
      Analysis Georeferencing Accuracy (SAGA) protocol) to classify the spatial
      resolution of museum records specifically for building improved SDMs. We used the
      high-elevation plant Saxifraga austromontana Wiegand (Saxifragaceae) as a case
      study to test the effect of using this protocol when developing an SDM. In
      MAXENT, we generated and compared SDMs using a comprehensive occurrence dataset
      that had undergone three different levels of georeferencing: (1) trained using
      all publicly available herbarium records of the species, minus outliers (2)
      trained using herbarium records claimed to be previously georeferenced, and (3)
      trained using herbarium records that we have manually georeferenced to a <= 1-km
      resolution using the SAGA protocol. Model predictions of suitable habitat for S.
      austromontana differed greatly depending on georeferencing level. The SDMs fitted
      with presence locations georeferenced using SAGA outperformed all others.
      Differences among models were exacerbated for future distribution predictions.
      Under rapid climate change, accurately forecasting the response of species
      becomes increasingly important. Failure to georeference location data and cull
      inaccurate samples leads to erroneous model output, limiting the utility of
      spatial analyses. We present a simple, standardized georeferencing method to be
      adopted by curators, ecologists, and modelers to improve the geographic accuracy
      of museum records and SDM predictions.

PMID- 29321913
TI  - Egg size and emergence timing affect morphology and behavior in juvenile Chinook
      Salmon, Oncorhynchus tshawytscha.
AB  - Variation in early life history traits often leads to differentially expressed
      morphological and behavioral phenotypes. We investigated whether variation in egg
      size and emergence timing influence subsequent morphology associated with
      migration timing in juvenile spring Chinook Salmon, Oncorhynchus tshawytscha.
      Based on evidence for a positive relationship between growth rate and migration
      timing, we predicted that fish from small eggs and fish that emerged earlier
      would have similar morphology to fall migrants, while fish from large eggs and
      individuals that emerged later would be more similar to older spring yearling
      migrants. We sorted eyed embryos within females into two size categories: small
      and large. We collected early and late-emerging juveniles from each egg size
      category. We used landmark-based geometric morphometrics and found that egg size
      appears to drive morphological differences. Egg size shows evidence for an
      absolute rather than relative effect on body morphology. Fish from small eggs
      were morphologically more similar to fall migrants, while fish from large eggs
      were morphologically more similar to older spring yearling migrants. Previous
      research has shown that the body morphology of fish that prefer the surface or
      bottom location in a tank soon after emergence also correlates with the
      morphological variations between wild fall and spring migrants, respectively. We
      found that late-emerging fish spent more time near the surface. Our study shows
      that subtle differences in early life history characteristics may correlate with
      a diversity of future phenotypes.

PMID- 29321914
TI  - A hierarchical spatiotemporal analog forecasting model for count data.
AB  - Analog forecasting is a mechanism-free nonlinear method that forecasts a system
      forward in time by examining how past states deemed similar to the current state
      moved forward. Previous applications of analog forecasting has been successful at
      producing robust forecasts for a variety of ecological and physical processes,
      but it has typically been presented in an empirical or heuristic procedure,
      rather than as a formal statistical model. The methodology presented here extends
      the model-based analog method of McDermott and Wikle (Environmetrics, 27, 2016,
      70) by placing analog forecasting within a fully hierarchical statistical
      framework that can accommodate count observations. Using a Bayesian approach, the
      hierarchical analog model is able to quantify rigorously the uncertainty
      associated with forecasts. Forecasting waterfowl settling patterns in the
      northwestern United States and Canada is conducted by applying the hierarchical
      analog model to a breeding population survey dataset. Sea surface temperature
      (SST) in the Pacific Ocean is used to help identify potential analogs for the
      waterfowl settling patterns.

PMID- 29321915
TI  - Comparative genetics of invasive populations of walnut aphid, Chromaphis
      juglandicola, and its introduced parasitoid, Trioxys pallidus, in California.
AB  - Coevolution may be an important component of the sustainability of importation
      biological control, but how frequently introduced natural enemies coevolve with
      their target pests is unclear. Here we explore whether comparative population
      genetics of the invasive walnut aphid, Chromaphis juglandicola, and its
      introduced parasitoid, Trioxys pallidus, provide insights into the localized
      breakdown of biological control services in walnut orchards in California. We
      found that sampled populations of C. juglandicola exhibited higher estimates of
      genetic differentiation (FST) than co-occurring populations of T. pallidus. In
      contrast, estimates of both the inbreeding coefficient (GIS) and contemporary
      gene flow were higher for T. pallidus than for C. juglandicola. We also found
      evidence of reciprocal outlier loci in some locations, but none showed
      significant signatures of selection. Synthesis and applications. Understanding
      the importance of coevolutionary interactions for the sustainability of
      biological control remains an important and understudied component of biological
      control research. Given the observed differences in gene flow and genetic
      differentiation among populations of T. pallidus and C. juglandicola, we suspect
      that temporary local disruption of biological control services may occur more
      frequently than expected while remaining stable at broader regional scales.
      Further research that combines genomewide single nucleotide polymorphism
      genotyping with measurements of phenotypic traits is needed to provide more
      conclusive evidence of whether the occurrence of outlier loci that display
      significant signatures of selection can be interpreted as evidence of the
      presence of a geographic mosaic of coevolution in this system.

PMID- 29321916
TI  - A spatiotemporal analysis of acoustic interactions between great reed warblers
      (Acrocephalus arundinaceus) using microphone arrays and robot audition software
      HARK.
AB  - Acoustic interactions are important for understanding intra- and interspecific
      communication in songbird communities from the viewpoint of soundscape ecology.
      It has been suggested that birds may divide up sound space to increase
      communication efficiency in such a manner that they tend to avoid overlap with
      other birds when they sing. We are interested in clarifying the dynamics
      underlying the process as an example of complex systems based on short-term
      behavioral plasticity. However, it is very problematic to manually collect
      spatiotemporal patterns of acoustic events in natural habitats using data derived
      from a standard single-channel recording of several species singing
      simultaneously. Our purpose here was to investigate fine-scale spatiotemporal
      acoustic interactions of the great reed warbler. We surveyed spatial and temporal
      patterns of several vocalizing color-banded great reed warblers (Acrocephalus
      arundinaceus) using an open-source software for robot audition HARK (Honda
      Research Institute Japan Audition for Robots with Kyoto University) and three new
      16-channel, stand-alone, and water-resistant microphone arrays, named DACHO
      spread out in the bird's habitat. We first show that our system estimated the
      location of two color-banded individuals' song posts with mean error distance of
      5.5 +/- 4.5 m from the location of observed song posts. We then evaluated the
      temporal localization accuracy of the songs by comparing the duration of
      localized songs around the song posts with those annotated by human observers,
      with an accuracy score of average 0.89 for one bird that stayed at one song post.
      We further found significant temporal overlap avoidance and an asymmetric
      relationship between songs of the two singing individuals, using transfer
      entropy. We believe that our system and analytical approach contribute to a
      better understanding of fine-scale acoustic interactions in time and space in
      bird communities.

PMID- 29321917
TI  - Corrigendum.
AB  - [This corrects the article DOI: 10.1002/ece3.1879.].

PMID- 29321919
TI  - Addressing the recruitment shortfall in surgery - How do we inspire the next
      generation?
AB  - *Application rates to surgery by medical students have declined in recent
      years.*More hands-on experience, information and mentorship is needed in medical
      schools.*Within surgery, gendered stereotyping of roles and environments must be
      challenged.*Reform of the current systems of outcome reporting is necessary.

PMID- 29321918
TI  - Reproductive management in dairy cows - the future.
AB  - Background: Drivers of change in dairy herd health management include the
      significant increase in herd/farm size, quota removal (within Europe) and the
      increase in technologies to aid in dairy cow reproductive management. Main body:
      There are a number of key areas for improving fertility management these include:
      i) handling of substantial volumes of data, ii) genetic selection (including
      improved phenotypes for use in breeding programmes), iii) nutritional management
      (including transition cow management), iv) control of infectious disease, v)
      reproductive management (and automated systems to improve reproductive
      management), vi) ovulation / oestrous synchronisation, vii) rapid diagnostics of
      reproductive status, and viii) management of male fertility. This review covers
      the current status and future outlook of many of these key factors that
      contribute to dairy cow herd health and reproductive performance. Conclusions: In
      addition to improvements in genetic trends for fertility, numerous other future
      developments are likely in the near future. These include: i) development of new
      and novel fertility phenotypes that may be measurable in milk; ii) specific
      fertility genomic markers; iii) earlier and rapid pregnancy detection; iv)
      increased use of activity monitors; v) improved breeding protocols; vi) automated
      inline sensors for relevant phenotypes that become more affordable for farmers;
      and vii) capturing and mining multiple sources of "Big Data" available to dairy
      farmers. These should facilitate improved performance, health and fertility of
      dairy cows in the future.

PMID- 29321920
TI  - Impact of medial-to-lateral vs lateral-to-medial approach on short-term and
      cancer-related outcomes in laparoscopic colorectal surgery: A retrospective
      cohort study.
AB  - Background: Laparoscopic surgery is the favoured method of colorectal cancer
      resections. It is surgeon expertise and discretion to choose whether to mobilize
      colon lateral-to-medial or medial-to-lateral. We aim to identify the advantage of
      one approach over the other in short-term and cancerrelated outcomes. Methods: A
      retrospective review of a prospectively maintained database of all laparoscopic
      colorectal resections with curative-intent, in a single unit, from March 2013 to
      October 2014. Data was collected on patient demographics, method of laparoscopic
      mobilisation, operating time, length-of-stay, post-operative complications,
      clearance of circumferential resection margins lymph node harvest and follow-up.
      Results: 137 patients with comparable patient demographics had laparoscopic
      colorectal cancer resection. 76 (60.3%) male and 50 (39.7%) female patients.
      58(46.0%) of resections were performed using medial-to-lateral approach, while
      68(54.0%) lateral-to-medial. Lateral group had on average 14(0-38) lymph nodes
      with specimen compared to 17 (6-45) in medial group. There was a statistically
      significant difference in the major complication rate (Clavien-Dindo IV) between
      the groups with 1(1.7%) in the medial-to-lateral group compared to 7 (10.2%) in
      the lateral-to-medial group, (p .035). Patients in the medial-to-lateral group
      had median length-of-stay of 7 days (range 2-55) compared to 7 days (range 2-75)
      in the lateral-to-medial group. There was no statistically significant difference
      in survival between both groups up-to 1334 days p=.413. Conclusion: Our study
      shows that mobilising the colon medially in laparoscopic colorectal cancer
      resection increases the lymph node harvest, gives comparable CRM clearance,
      similar length of hospital stay and complications. It makes no statistically
      significant difference in the overall patient survival.

PMID- 29321921
TI  - Farming, Q fever and public health: agricultural practices and beyond.
AB  - Since the Neolithic period, humans have domesticated herbivores to have food
      readily at hand. The cohabitation with animals brought various advantages that
      drastically changed the human lifestyle but simultaneously led to the emergence
      of new epidemics. The majority of human pathogens known so far are zoonotic
      diseases and the development of both agricultural practices and human activities
      have provided new dynamics for transmission. This article provides a general
      overview of some factors that influence the epidemic potential of a zoonotic
      disease, Q fever. As an example of a disease where the interaction between the
      environment, animal (domestic or wildlife) and human populations determines the
      likelihood of the epidemic potential, the management of infection due to the Q
      fever agent, Coxiella burnetii, provides an interesting model for the application
      of the holistic One Health approach.

PMID- 29321922
TI  - Longitudinal pharmacoepidemiological and health services research for substance
      users in treatment: protocol of the Belgian TDI-IMA linkage.
AB  - Background: Not much is known about the health seeking behavior of people with
      substance use disorders before they enter specialized treatment and afterwards.
      This paper explains in detail the protocol that has been followed to establish
      the Belgian TDI-IMA-database, which is linking two separate databases: the
      Treatment Demand Indicator (TDI) and the database of the Intermutualistic Agency
      (IMA). The Treatment Demand Indicator is measuring incidence of people with
      substance use disorders entering drug treatment. The IMA-database covers data,
      collected in the framework of the compulsory Belgian health care and benefits
      insurance program, on reimbursed medication and the use of reimbursed health
      services. The linkage results in pharmacoepidemiological and health service data
      for people who were in treatment for substance use disorders and for a group of
      comparators. Methods: The TDI-database was linked to the IMA-database for the
      period between 01/01/2008 and 31/12/2017, based on the national identification
      number of patients who have been in alcohol or drug treatment between 01/01/2011
      and 31/12/2014. Through this linkage, pharmacoepidemiological and health service
      data became available for at least 3 years before the first registered episode in
      the TDI-database till at least 3 years after the first episode. For each person
      in TDI four comparators, who were not in specialized treatment, were matched on
      age, sex and place of residence. Discussion: The TDI-IMA-database allows for an
      analysis of health seeking behavior and health care pathways of people before and
      after they entered specialized alcohol and drug treatment. The presented protocol
      could be used in other European countries to establish a linkage between existing
      health databases. This will allow for a better understanding of the health care
      needs of patients with substance use disorders.

PMID- 29321923
TI  - Idiopathic pulmonary vein thrombosis?
AB  - Idiopathic pulmonary vein thrombosis (PVT) is a rare disease which is likely
      under-diagnosed because of nebulous presentations. Accurate diagnosis is
      essential to prevent complications.

PMID- 29321924
TI  - Lung Mycobacterium avium developed after removing an acupuncture needle from the
      lung.
AB  - Acupuncture needles can cause non-tuberculosis mycobacteria (NTM) infection on
      the skin, but there are no reports that acupuncture needles inserted into the
      lung have caused lung NTM infection. A 63-year-old woman, who underwent removal
      of a broken acupuncture needle inserted into the lung nine years ago, was
      admitted with nodules in the right lung. The shadow was positioned where the
      needle had existed. Partial lung resection of the right lower lobe was performed,
      and the resected area showed caseous necrosis histopathologically. Furthermore,
      Mycobacterium avium was cultured from the specimen. When abnormal lung shadows
      are located where a resected foreign body appeared, NTM infection should be
      considered.

PMID- 29321925
TI  - Lupus pneumonitis presenting with high titre of anti-Ro antibody.
AB  - Lupus pneumonitis carries high mortality and is a rare manifestation of systemic
      lupus erythematosus (SLE). However, it is difficult to diagnose and is often
      mistaken as pneumonia, alveolar haemorrhage, or organizing pneumonia. Previous
      studies demonstrated that serum anti-Ro antibodies are elevated more frequently
      in SLE patients with pneumonitis than in those without. We report a 21-year-old
      female who was newly diagnosed as having SLE with nephritis and who suddenly
      developed right lung opacity and rapidly progressed to severe hypoxaemia despite
      the use of broad-spectrum antibiotics. The serum titre of anti-Ro antibody was
      greater than 240 U/mL. She underwent lung biopsy and lupus pneumonitis was
      confirmed by the pathological findings. Subsequently, she showed a favourable
      response to plasma exchange, steroid pulse therapy, and mycophenolate mofetil
      (MMF) treatment. For SLE patients with pulmonary infiltrates, high degree of
      clinical suspicion of lupus pneumonitis is required and measurement of serum anti
      Ro antibody may help to make the diagnosis.

PMID- 29321926
TI  - Lung injury associated with electronic cigarettes inhalation diagnosed by
      transbronchial lung biopsy.
AB  - A 46-year-old healthy man developed respiratory distress, night sweats, fever,
      and weight loss after using electronic cigarettes (e-cigs) for approximately 1
      month. He presented to the hospital when the symptoms worsened 2 months after
      onset. The findings of bronchoalveolar lavage (BAL) fluid examination and the
      following transbronchial lung biopsy examination led to the diagnosis of acute
      alveolitis: intra-alveolar fibrosis accompanied with exudate containing abundant
      lipid-laden macrophages, eosinophils, and neutrophils. Eventually, e-cig-induced
      acute lung injury was diagnosed. The symptoms were rapidly alleviated upon e-cig
      use termination and methylprednisolone pulse therapy, and no subsequent
      recurrence was observed. There have been only a few reported cases of e-cig
      induced lung injury. In e-cig users presenting with atypical pneumonia, close
      examination by BAL and biopsy should be performed to verify the presence or
      absence of lipid-laden macrophages.

PMID- 29321927
TI  - Pulmonary nocardiosis in a patient with idiopathic CD4 T-lymphocytopenia.
AB  - Idiopathic CD4 T-lymphocytopenia (ICL) is a rare immunodeficiency characterized
      by low CD4 T-lymphocyte count, which usually manifests with opportunistic
      infections. Nocardia as an opportunistic pathogen infecting patients with this
      condition has rarely been reported. Here, we describe the case of a 46-year-old
      male who presented with lung mass and respiratory and systemic symptoms and was
      eventually diagnosed with pulmonary nocardiosis. A workup for predisposing
      immunodeficiencies suggested a picture of ICL. This case illustrates the
      importance of considering ICL as a possible predisposing condition when an
      otherwise healthy individual presents with pulmonary nocardiosis.

PMID- 29321928
TI  - Lung cancer development in the patient with granulomatosis with polyangiitis
      during long term treatment with cyclophosphamide: first documented case.
AB  - A 65-year-old man was diagnosed with granulomatosis with polyangiitis (GPA) at
      the age of 47, when cytoplasmic anti-neutrophil cytoplasmic antibody (C-ANCA)
      serology was positive, and he had multiple nodular shadows in both lungs. He had
      been treated with prednisolone, cyclophosphamide (CPA) and plasma exchange. At
      the age of 64, a nodular shadow was newly detected in the right lower lung field
      and serum tumour marker increased. Subsequent positron emission
      tomography/computed tomography scan demonstrated accumulations of
      fluorodexyglucose (FDG) in the same area, mediastinum lymph nodes, thoracic wall,
      right iliac bone, and right retroperitoneum. The diagnosis of squamous cell lung
      cancer cT2bN2M1b Stage4 was made with endobronchial ultrasound-guided
      transbronchial needle aspiration (EBUS-TBNA). There are no reports of cases that
      lung cancer has developed with GPA during the long-term treatment with CPA. We
      suggest that in such patients, the differential diagnosis should include not only
      the relapse of GPA, but also the rare possibility of development of carcinomas.

PMID- 29321929
TI  - Pleuritis associated with primary Sjogren syndrome.
AB  - We herein present a case of a 71-year-old woman with primary Sjogren's syndrome
      (SjS), who developed bilateral pleural effusion and ground glass opacity during
      treatment with low-dose prednisolone. The pleural effusion and bronchoalveolar
      lavage fluid revealed elevation of lymphocytes. Thoracoscopic pleural biopsy
      showed infiltration of lymphocytes with no evidence of other diseases, confirming
      SjS-related pleuritis. Therefore, we initiated 20 mg prednisolone and pleural
      effusion was rapidly resolved. Our results indicate that SjS can be rarely
      complicated with pleuritis. In addition, thoracoscopic pleural biopsy and a rapid
      response to steroid treatment would be helpful for diagnosing SjS-related
      pleuritis.

PMID- 29321930
TI  - A case of pulmonary cyst and pneumothorax after bronchial thermoplasty.
AB  - Bronchial thermoplasty (BT) is a bronchoscopic treatment for severe asthma using
      thermal energy to reduce smooth muscle in the bronchial wall. A 47-year-old man
      underwent BT for uncontrolled severe asthma despite maximal pharmacological
      treatment. After a third procedure, he experienced hypoxaemia because of complete
      bilateral upper lobe atelectasis. A pulmonary cyst suddenly emerged in to the
      right middle lobe, associated with the pneumothorax on postoperative day 6, and a
      chest drainage tube was inserted. As atelectasis of the right upper lung suddenly
      improved on postoperative day 12, pneumothorax and the cyst improved. Excess
      stress on the middle lobe due to upper lobe collapse, and check valve due to
      airway oedema and phlegm, might be related to pulmonary cyst formation. Tissue
      fragility related to systemic steroid usage and pressure load during pulmonary
      function testing might influence the occurrence of pneumothorax. Severe adverse
      events under complete atelectasis after BT require careful attention.

PMID- 29321931
TI  - Novel hybrid cryo-radial method: an emerging alternative to CT-guided biopsy in
      suspected lung cancer. A prospective case series and description of technique.
AB  - In diagnosing peripheral pulmonary lesions (PPL), radial endobronchial ultrasound
      (R-EBUS) is emerging as a safer method in comparison to CT-guided biopsy. Despite
      the better safety profile, the yield of R-EBUS remains lower (73%) than CT-guided
      biopsy (90%) due to the smaller size of samples. We adopted a hybrid method by
      adding cryobiopsy via the R-EBUS Guide Sheath (GS) to produce larger, non-crushed
      samples to improve diagnostic capability and enhance molecular testing. We report
      six prospective patients who underwent this procedure in our institution. R-EBUS
      samples were obtained via conventional sampling methods (needle aspiration,
      forceps biopsy, and cytology brush), followed by a cryobiopsy. An endobronchial
      blocker was placed near the planned area of biopsy in advance and inflated post
      biopsy to minimize the risk of bleeding in all patients. A chest X-ray was
      performed 1 h post-procedure. All the PPLs were visualized with R-EBUS. The mean
      diameter of cryobiopsy samples was twice the size of forceps biopsy samples. In
      four patients, cryobiopsy samples were superior in size and the number of
      malignant cells per high power filed and was the preferred sample selected for
      mutation analysis and molecular testing. There was no pneumothorax or significant
      bleeding to report. Cryobiopsy samples were consistently larger and were the
      preferred samples for molecular testing, with an increase in the diagnostic yield
      and reduction in the need for repeat procedures, without hindering the marked
      safety profile of R-EBUS. Using an endobronchial blocker improves the safety of
      this procedure.

PMID- 29321932
TI  - Acute onset of ulcerative colitis during chemoradiotherapy for anaplastic
      lymphoma kinase-positive lung adenocarcinoma.
AB  - We report a case of acute onset of ulcerative colitis (UC) during
      chemoradiotherapy in a patient with anaplastic lymphoma kinase (ALK)-positive
      lung adenocarcinoma. A 46-year-old male patient with an abnormal chest shadow was
      referred to our hospital. He was diagnosed with lung adenocarcinoma, clinical
      stage T1aN3M0 and stage IIIB. Concurrent chemoradiotherapy was selected for his
      initial therapy. After two cycles of cisplatin and vinorelbine administration, he
      experienced persistent diarrhoea and anorexia. Findings of the colonoscopy
      revealed a pancolitis type of UC. After discontinuation of chemotherapy, oral
      administration of mesalazine was initiated. The development of UC during
      chemotherapy is very rare and only a few case reports have been published.
      Although adverse events are rare, it is very important to assess the colitis
      precisely by performing a colonoscopy when protracted abdominal pain is
      experienced by the patient, along with diarrhoea or bloody stool during
      chemotherapy.

PMID- 29321933
TI  - Acute progression of aspergillosis in a patient with lung cancer receiving
      nivolumab.
AB  - A 65-year-old man with chronic progressive pulmonary aspergillosis (CPPA) was
      admitted for the treatment of lung adenocarcinoma while receiving an immune
      checkpoint inhibitor, nivolumab. The tumour responded well to the therapy, but
      the cavity of CPPA became large in contrast to the tumour after 20 courses of
      therapy. He was diagnosed as having exacerbation of CPPA and successfully and
      concurrently treated with an antifungal agent and nivolumab. Since there was
      absence of obvious immunosuppression and the presence of a drastic effect on
      tumour remission during nivolumab therapy, this phenomenon suggested that the
      trigger of CPPA progression was dependent not on immunosuppression but on a
      hyperreaction to microorganisms, which was similar to the immune reconstitution
      inflammatory syndrome caused by nivolumab. This was a thought-provoking case in
      which the immune checkpoint inhibitor had a paradoxical effect for the tumour and
      infection.

PMID- 29321934
TI  - An elderly woman with a mediastinal granulosa cell tumour: a rare presentation.
AB  - Mediastinal lesions occur in a wide variety of clinical conditions. Metastatic
      granulosa cell tumour (GCT) in the mediastinum is a rare occurrence. We report a
      case of a woman who had a metastatic (GCT) in her mediastinum 40 years after
      treatment of the initial neoplasm. Surgical resection of the mediastinal mass
      revealed a low-grade epithelioid neoplasm with coffee bean-shaped nuclei and
      immunohistochemical stains that were consistent with metastatic GCT.

PMID- 29321935
TI  - Desquamative interstitial pneumonia complicated by diffuse alveolar haemorrhage.
AB  - We report a rare case of desquamative interstitial pneumonia (DIP) with diffuse
      alveolar haemorrhage (DAH). A 56-year-old man diagnosed with DIP by surgical lung
      biopsy 2 years ago was admitted to our hospital because of severe acute
      respiratory failure. The DIP had progressed despite smoking cessation. On
      admission, the patient appeared extremely ill, and physical examination revealed
      respiratory distress. The patient required mechanical ventilation. High
      resolution computed tomography showed diffuse ground glass opacity in both lungs.
      The bronchoalveolar lavage fluid was bloody, and numerous haemosiderin-laden
      alveolar macrophages were detected. Pulse steroid therapy followed by oral
      prednisolone immediately relieved the respiratory failure and improved the long
      term control of the DIP. Paired sera tests confirmed the diagnosis of influenza
      A/H3N2 virus infection, which was the cause of the DAH. Chronically progressive
      DIP with acute respiratory failure due to DAH was successfully treated by steroid
      therapy.

PMID- 29321936
TI  - Low-voltage electricity-induced lung injury.
AB  - We report a case of bilateral pulmonary infiltrates and haemoptysis following low
      voltage electricity exposure in an agricultural worker. A 58-year-old man
      standing in water reached for an electric watering machine and sustained an
      exposure to 220 V circuit for an uncertain duration. The electricity was turned
      off by another worker, and the patient was asymptomatic for the next 10 h until
      he developed haemoptysis. A chest radiograph demonstrated bilateral infiltrates,
      and chest computed tomography (CT) revealed ground-glass opacities with
      interstitial thickening. Evaluations, including electrocardiogram, serum
      troponin, N-terminal pro-B-type natriuretic peptide (NT-pro BNP), coagulation
      studies, and echocardiogram, found no abnormality. The patient was treated for
      suspected electricity-induced lung injury and bleeding with tranexamic acid and
      for rhabdomyolysis with volume resuscitation. He recovered with complete
      resolution of chest radiograph abnormalities by Day 7. This is the first reported
      case of bilateral lung oedema and/or injury after electricity exposure without
      cardiac arrest.

PMID- 29321937
TI  - Marijuana "bong" pseudomonas lung infection: a detrimental recreational
      experience.
AB  - The use of Cannabis sativa, also known as marijuana, is believed to have dated
      back to thousands of years B.C. More than 200 decades later, it remains a popular
      recreational psychoactive substance that can be smoked through a water pipe. We
      report a case of marijuana smoking via a "bong" device, which has resulted in
      severe Pseudomonas aeruginosa necrotizing pneumonia treated with conservative
      medical therapy. This case highlights the importance of recognizing that life
      threatening pneumonia can potentially be linked to marijuana and "bong" usage.
      Complicated cases should be considered for early surgical intervention.

PMID- 29321939
TI  - Isolation of Rickettsia amblyommatis in HUVEC line.
AB  - Rickettsia amblyommatis, formerly named Rickettsia amblyommii and 'Candidatus
      Rickettsia amblyommii' is an intracellular bacterium belonging to the spotted
      fever group Rickettsia. It is highly prevalent in Amblyomma americanum and in
      other Amblyomma spp. throughout the Western Hemisphere. R. amblyommatis has been
      cultivated in chicken fibroblast, primary embryonated chicken eggs, Vero cells
      and arthropod-derived cells. Because of the affinity of rickettsiae to invade
      vascular endothelial cells, we tried to isolate R. amblyommatis from a nymph of
      Amblyomma cajennense s.l. collected in Saltillo (Coahulia, Mexico) using human
      umbilical vein endothelial cells (HUVEC). One tick half was analysed by ompA PCR
      and was found to be positive for R. amblyommatis. The other half was selected for
      in vitro culture of Rickettsia spp. It was triturated in 1 mL of endothelial cell
      growth medium with 1% antibiotic-antimycotic solution, and the homogenate was
      inoculated into a HUVEC line. Culture was maintained at 33 degrees C in
      endothelial cell growth medium plus 2 mM l-glutamine and 2% fetal calf serum,
      with 5% CO2. The medium was changed weekly. Culture was checked by Gimenez stain
      for Rickettsia-like intracellular organisms. After 48 days of incubation,
      Rickettsia-like organisms were observed in HUVEC. PCR assays and sequencing of
      ompA gene in the culture suspension showed 100% identity with R. amblyommatis.
      This isolate was successfully established in HUVEC, and it has been deposited in
      the collection of the Center of Rickettsioses and Arthropod-Borne Diseases,
      Infectious Diseases Department, Hospital San Pedro-Center of Biomedical Research
      from La Rioja, Logrono, Spain. The HUVEC line is a useful tool for the isolation
      of R. amblyommatis.

PMID- 29321940
TI  - 'Lactomassilus timonensis,' a new anaerobic bacterial species isolated from the
      milk of a healthy African mother.
AB  - We here report the main characteristics of a new anaerobic bacterial genus and
      species 'Lactomassilus timonensis,' strain Marseille-P4641T (CSUR = P4641),
      isolated by microbial culturomics from the milk of a 35-year-old healthy
      lactating mother from Mali.

PMID- 29321938
TI  - Noncontiguous finished genome sequence and description of Mediterranea
      massiliensis gen. nov., sp. nov., a new member of the Bacteroidaceae family
      isolated from human colon.
AB  - Strain Marseille-P2645T was isolated in a colon sample from a Frenchwoman who
      underwent a colonoscopy. Bacterial cells were Gram negative, non-spore forming,
      mobile and strictly anaerobic. The genome of strain Marseille-P2645T is 3 950 441
      bp long and contains 3374 protein-coding genes. The DNA G+C content is of 51.66
      mol%. Strain Marseille-P2645T exhibited a 92.9% sequence similarity with
      Bacteroides helcogenes strain P36-108T (GenBank accession no. CP002352), the
      phylogenetically closest species with standing in nomenclature. Strain Marseille
      P2645T (= CSUR P2645 = DSM 103034) is therefore a candidate as a type species of
      a new genus belonging to the Bacteroidaceae family, for which the name of
      Mediterranea massiliensis gen. nov., sp. nov., is proposed.

PMID- 29321941
TI  - Hygienic measures during animal transport to abattoirs - a status quo analysis of
      the current cleaning and disinfection of animal transporters in Germany.
AB  - Background: The process of cleaning and disinfection of animal transport vehicles
      after unloading animals at the abattoir is a critical control point regarding
      proper hygiene. It is an important step regarding the biosecurity. In the present
      study, a status quo analysis of the currently performed cleaning and disinfection
      measures of animal transport vehicles was carried out at the vehicle washing
      facilities of five different industrial abattoirs in Germany. For this purpose, a
      checklist was developed and validated to assess the washing procedure of
      transport vehicles in a standardised way. The evaluated phases of cleaning
      included the evaluation criteria "length of time per used floor", "visual
      cleaning success" and the "hygienic awareness of the driver". During
      disinfection, attention was paid to the internal and external surfaces of the
      transporter and to the methods used to disinfect them. In addition, the technical
      and structural equipment of the five different washing facilities were recorded
      using a questionnaire and compared to the legal regulations, respectively. At
      each location, approximately 150 vehicles of all delivery types (transport
      vehicles owned by the abattoir, external delivery companies and vehicles owned by
      the supplying farmers) were inspected so that in total a number of more than 750
      vehicles were included in this study. The aim was to develop abattoir specific,
      as well as generally applicable intervention measures and to generate "standard
      operation procedures" (SOP's) for the cleaning and disinfection of animal
      transporters. Results: At two out of five locations vehicles have left the
      abattoir without cleaning and disinfection. In 31-97% of all vehicles, only a
      cleaning of the vehicle was carried out, a subsequent disinfection did not take
      place. A cleaning followed by disinfecting took place in only 3-59% of all
      vehicles. Conclusion: The results indicate a considerable need for improvement
      and standardisation in this relevant field of disease prevention.

PMID- 29321942
TI  - Preventing stress-related ill health among newly registered nurses by supporting
      engagement in proactive behaviors: development and feasibility testing of a
      behavior change intervention.
AB  - Background: Transitioning into a new professional role is a stressful experience
      with consequences for mental and physical health, job satisfaction,
      organizational commitment, and turnover. New registered nurses seem to be at
      particular risk of developing stress-related ill health during their first years
      in the profession. Previous research indicates that engagement in proactive
      behaviors may reduce this risk. Methods: With the work presented in this paper,
      we aimed to test the feasibility of conducting an evaluation of the effect of a
      behavior change intervention to prevent stress-related ill health among new
      registered nurses by supporting their engagement in proactive behaviors.
      Feasibility objectives included recruitment, randomization, data collection and
      analysis, participation, acceptability, and deliverability.We tested the
      feasibility of evaluating the effect of the intervention as part of a transition
      to-practice program for new registered nurses using a non-randomized design with
      one condition. The trial included a sample of 65 new registered nurses who had
      been working for 6 months or less. Results: The feasibility of conducting a full
      scale effect evaluation was confirmed for recruitment, data collection and
      analysis, participation, and acceptability. It was not possible to randomize
      participants, but analyses of between-group differences revealed no selection
      bias. The time of the intervention will need to be extended to ensure the
      deliverability. Conclusion: With some adjustments in the study design, it is
      feasible to evaluate the effect of a behavior change intervention to support new
      registered nurses' engagement in proactive behaviors during their transition into
      the new profession as part of a transition-to-practice program for new nurses.

PMID- 29321943
TI  - Tenecteplase compared with streptokinase and heparin in the treatment of
      pulmonary embolism: an observational study.
AB  - Background: Thrombolytics are recommended in high risk patients with massive
      pulmonary embolism (PE). However, clinical practice seems to be far different and
      questions related to its utility in less severely affected patients remain the
      subject of investigation. The objective of this observational study was to
      compare the efficacy and safety of tenecteplase with streptokinase and heparin.
      Method: A total of 103 patients (tenecteplase: 62, streptokinase: 17, heparin:
      24) diagnosed with PE (massive: 33 [32.04%], submassive: 50 [48.54%], and minor:
      20 [19.42%]) were included. Results: Mean age was 50.04 years and major risk
      factors were immobilization due to hospitalization, history of deep vein
      thrombosis, and diabetes. Common clinical symptoms of dyspnoea, right ventricular
      dysfunction, and cough were found in 94.17%, 81.55%, and 77.67% patients,
      respectively. Between treatment and day 7, death occurred in 4.84%, 5.88%, and
      8.33% patients in the tenecteplase, streptokinase, and heparin groups,
      respectively. The differences among treatment groups were non-significant (p >
      .05). All treatments have demonstrated significant alleviation of dyspnoea and
      heart rate (p < .05). Significant (p < .05) increase in oxygen saturation was
      seen and it was markedly higher in the tenecteplase-treated patients compared
      with the streptokinase- and heparin-treated patients. By day 7, there was 100%
      resolution of right bundle branch block only in the tenecteplase group. No
      intracranial bleeding or fatal bleeding episodes were found in any group.
      Conclusion: Tenecteplase was found to be effective in patients with PE
      irrespective of their clinical status and no major adverse events were noted.

PMID- 29321944
TI  - Myelomeningocele with Unilateral Right Renal Agenesis: A Case Report.
AB  - Congenital anomalies of the spine may occur with malformations of the central
      nervous, cardiovascular, gastrointestinal, respiratory, and genitourinary
      systems. This is a case of myelomeningocele with unilateral right renal agenesis
      in a newborn. The patient suffered complications of cerebrospinal fluid leak and
      meningitis, but was successfully treated and discharged on day 86. In this case,
      unilateral right renal agenesis represented a significant surgical risk because
      failure of the remaining kidney could result in renal failure. Because congenital
      anomalies of the spine may be associated with malformations of the genitourinary
      system, and additional surgeries were necessary in our case following birth, it
      is very important that the presence of genitourinary malformations be evaluated.

PMID- 29321945
TI  - Gaze Compensation as a Technique for Improving Hand-Eye Coordination in
      Prosthetic Vision.
AB  - Purpose: Shifting the region-of-interest within the input image to compensate for
      gaze shifts ("gaze compensation") may improve hand-eye coordination in visual
      prostheses that incorporate an external camera. The present study investigated
      the effects of eye movement on hand-eye coordination under simulated prosthetic
      vision (SPV), and measured the coordination benefits of gaze compensation.
      Methods: Seven healthy-sighted subjects performed a target localization-pointing
      task under SPV. Three conditions were tested, modeling: retinally stabilized
      phosphenes (uncompensated); gaze compensation; and no phosphene movement (center
      fixed). The error in pointing was quantified for each condition. Results: Gaze
      compensation yielded a significantly smaller pointing error than the
      uncompensated condition for six of seven subjects, and a similar or smaller
      pointing error than the center-fixed condition for all subjects (two-way ANOVA, P
      < 0.05). Pointing error eccentricity and gaze eccentricity were moderately
      correlated in the uncompensated condition (azimuth: R2 = 0.47; elevation: R2 =
      0.51) but not in the gaze-compensated condition (azimuth: R2 = 0.01; elevation:
      R2 = 0.00). Increased variability in gaze at the time of pointing was correlated
      with greater reduction in pointing error in the center-fixed condition compared
      with the uncompensated condition (R2 = 0.64). Conclusions: Eccentric eye position
      impedes hand-eye coordination in SPV. While limiting eye eccentricity in
      uncompensated viewing can reduce errors, gaze compensation is effective in
      improving coordination for subjects unable to maintain fixation. Translational
      Relevance: The results highlight the present necessity for suppressing eye
      movement and support the use of gaze compensation to improve hand-eye
      coordination and localization performance in prosthetic vision.

PMID- 29321946
TI  - Clinical and Radiologic Considerations for Idiopathic Superior Mesenteric Artery
      Syndrome.
AB  - Superior mesenteric artery (SMA) syndrome often occurs in the setting of rapid
      weight loss and scoliosis corrective spinal surgery. A reduction of fat around
      the third part of the duodenum can predispose the duodenum to compression and
      obstruction by the SMA as it emerges from the abdominal aorta. In this report, we
      describe this underdiagnosed condition in a previously healthy young female
      presenting with progressive post-prandial emesis, non-specific abdominal pain,
      and weight loss. A critical review of this disease process is explored to
      highlight pathology, imaging characteristics, and essential alternative
      diagnostic considerations. We also discuss potential complications and current
      treatment strategies. SMA syndrome poses unique diagnostic challenges, and an
      awareness of its clinical presentation can further improve patient outcomes and
      avoid potentially life-threatening complications.

PMID- 29321947
TI  - Portal Vein Thrombosis Due to an Increase in Dose of Testosterone in a Young Man
      with Klinefelter Syndrome.
AB  - Klinefelter syndrome (KS) is associated with increased incidence of thrombotic
      events. Hypofibrinolysis is associated with increased risk of thromboembolism.
      Although testosterone replacement therapy (TRT) inhibits the hypofibrinolysis, it
      can still cause thrombosis paradoxically due to increased dose and duration of
      use. Herein, we present a case of a young male diagnosed with KS who was taking
      testosterone. The dose was increased to boost the energy levels, and the patient
      presented with abdominal pain. Computed tomography (CT) of the abdomen showed
      extensive portal vein thrombosis. He was started on enoxaparin followed by
      apixaban. Studies need to be done regarding the need for thromboembolism
      prophylaxis in patients on TRT.

PMID- 29321948
TI  - Performance of an Annular Closure Device in a 'Real-World', Heterogeneous, At
      Risk, Lumbar Discectomy Population.
AB  - Study design/setting Retrospective analysis of single-center registry outcomes
      data. Objective Assess the utility of an annular closure device (ACD) as an
      adjunct to limited discectomy for lumbar disc herniation (LDH). Background
      Recurrent lumbar disc herniation (rLDH) following limited discectomy persists at
      clinically significant rates, especially in large annular defect (at least 6 mm
      width) patients. While the etiology of reherniation is often multifactorial,
      inadequate annular occlusion remains one of the foremost considerations.
      Accordingly, annular closure has emerged as a promising technique and is the
      focus of this analysis. Methods This was a retrospective analysis of 171 patients
      who underwent limited lumbar discectomy with an ACD for LDH. Standardized patient
      assessment was performed preoperatively, three months postoperatively, and 12
      months postoperatively, in addition to self-presented visits. No minimum last
      follow-up was required for inclusion. Oswestry Disability Index (ODI) and Visual
      Analog Scale (VAS Leg/Back) pain scores were collected at all visits. Plain
      radiographs were obtained at all visits, with magnetic resonance imaging (MRI)
      scans performed annually and/or when patients presented as symptomatic. ACD
      related complications due to partial or complete mesh detachment from the
      titanium anchor were reported. All secondary surgical interventions were also
      reported. The Wilcoxon Rank-sum test was used to compare outcomes and events
      between sub-groups (p < 0.05). Results Mean last follow-up for all patients was
      15 months. Large annular defects were present in 154 patients (90%). Symptomatic
      reherniations were observed in six patients (3.5%; five were present in the large
      annular defect subpopulation). All patients demonstrated clinically meaningful
      improvement in clinical outcome scores at both follow-up intervals. ACD mesh
      detachment was observed in 15 patients (8.8%; two underwent a subsequent surgical
      intervention). No symptomatic reherniations were observed in secondary herniation
      patients compared to six (4.1%) in the primary herniation group (p = 0.60).
      Conclusions Annular closure with the ACD results in clinically meaningful
      improvements in both primary and secondary LDH patients, with decreased rates of
      reherniation in high-risk patients compared to previous discectomy reports.

PMID- 29321949
TI  - Piercing of the Lumbocostal Ligament by the Subcostal Nerve: A Previously
      Unreported Case.
AB  - As lateral approaches gain popularity in lumbar spine surgery, detailed
      discussions regarding anatomical variations in the innervation of the
      thoracolumbar region are of increasing importance. Damage to intercostal or
      subcostal nerves can lead to post-operative complications including regional loss
      of sensitivity, motor function, or abdominal wall hernias. More specifically, the
      subcostal nerve has been identified in the literature as one of the more
      vulnerable structures during such procedures. A clear understanding of the
      position of the subcostal nerve relative to nearby anatomical structures is
      therefore important for medical professionals. We herein report a rare anatomical
      variation in which the subcostal nerve pierces the lumbocostal ligament.

PMID- 29321950
TI  - Manifestations of Renal Impairment in Fructose-induced Metabolic Syndrome.
AB  - Introduction International studies show an increased incidence of chronic kidney
      disease (CKD) in patients with metabolic syndrome (MS). It is assumed that the
      major components of MS - obesity, insulin resistance, dyslipidemia, and
      hypertension - are linked to renal damage through the systemic release of several
      pro-inflammatory mediators, such as uric acid (UA), C-reactive protein (CRP), and
      generalized oxidative stress. The aim of the present study was to investigate the
      extent of kidney impairment and manifestations of dysfunction in rats with
      fructose-induced MS. Methods We used a model of high-fructose diet in male Wistar
      rats with 35% glucose-fructose corn syrup in drinking water over a duration of 16
      weeks. The experimental animals were divided into two groups: control and high
      fructose drinking (HFD). Serum samples were obtained from both groups for
      laboratory study, and the kidneys were extracted for observation via light
      microscopy examination. Results All HFD rats developed obesity, hyperglycemia,
      hypertriglyceridemia, increased levels of CRP and UA (when compared to the
      control group), and oxidative stress with high levels of malondialdehyde and low
      levels of reduced glutathione. The kidneys of the HFD group revealed a
      significant increase in kidney weight in the absence of evidence of renal
      dysfunction and electrolyte disturbances. Under light microscopy, the kidneys of
      the HFD group revealed amyloid deposits in Kimmelstiel-Wilson-like nodules and
      the walls of the large caliber blood vessels, early-stage atherosclerosis with
      visible ruptures and scarring, hydropic change (vacuolar degeneration) in the
      epithelial cells covering the proximal tubules, and increased eosinophilia in the
      distant tubules when compared to the control group. Conclusion Under the
      conditions of a fructose-induced metabolic syndrome, high serum UA and CRP
      correlate to the development of early renal disorders without a clinical
      manifestation of renal dysfunction. These phenomena are of particular importance
      for assessing the risk of developing future CKD.

PMID- 29321951
TI  - Utility of the Phenacyl Protecting Group in Traceless Protein Semisynthesis
      through Ligation-Desulfurization Chemistry.
AB  - Semisynthesis of proteins via expressed protein ligation is a widely applicable
      method, even more so because of the possibility of ligation at non-cysteine sites
      using beta-mercapto amino acids that can be converted to the corresponding native
      amino acids by desulfurization. A drawback of this ligation- desulfurization
      approach is the removal of any unprotected native cysteine residues within the
      ligated protein segments. Here, we show that the phenacyl (PAc) moiety can be
      successfully used to protect cysteines within recombinantly generated protein
      segments. As such, this group was selectively appended onto cysteine side chains
      within bacterially expressed polypeptides following intein cleavage, which
      reveals a rather sensitive thioester at the C-terminus. The PAc group proved to
      be compatible with native chemical ligation, radical desulfurization, and reverse
      phase HPLC conditions, and was smoothly removed at the end. The utility of the
      PAc protecting group was then demonstrated by the 'traceless' semisynthesis of
      two proteins containing one or two native cysteines: human small heat shock
      protein Hsp27 and murine prion protein.

PMID- 29321952
TI  - Fasciculation and elongation zeta-1 protein (FEZ1) interacts with the retinoic
      acid receptor and participates in transcriptional regulation of the Hoxb4 gene.
AB  - Fasciculation and elongation zeta-1 (FEZ1) protein is involved in axon outgrowth
      and is highly expressed in the brain. It has multiple interaction partners, with
      functions varying from the regulation of neuronal development and intracellular
      transport mechanisms to transcription regulation. One of its interactors is
      retinoic acid receptor (RAR), which is activated by retinoic acid and controls
      many target genes and physiological process. Based on previous evidence
      suggesting a possible nuclear role for FEZ1, we wanted to deepen our
      understanding of this function by addressing the FEZ1-RAR interaction. We
      performed in vitro binding experiments and assessed the interface of interaction
      between both proteins. We found that FEZ1-RAR interacted with a similar magnitude
      as RAR to its responsive element DR5 and that the interaction occurred in the
      coiled-coil region of FEZ1 and in the ligand-binding domain of RAR. Furthermore,
      cellular experiments were performed in order to confirm the interaction and
      screen for induced target genes from an 86-gene panel. The analysis of gene
      expression showed that only in the presence of retinoic acid did FEZ1 induce
      hoxb4 gene expression. This finding is consistent with data from the literature
      showing the hoxb4 gene functionally involved in development and acute myeloid
      leukemia, as is FEZ1.

PMID- 29321953
TI  - Matrix metalloproteinase-1 facilitates MSC migration via cleavage of IGF-2/IGFBP2
      complex.
AB  - The specific mechanism underlying the tumor tropism of human mesenchymal stem
      cells (MSCs) for cancer is not well defined. We previously showed that the
      migration potential of MSCs correlated with the expression and protease activity
      of matrix metalloproteinase (MMP)-1. Furthermore, highly tumor-tropic MSCs
      expressed higher levels of MMP-1 and insulin-like growth factor (IGF)-2 than
      poorly migrating MSCs. In this study, we examined the functional roles of IGF-2
      and MMP-1 in mediating the tumor tropism of MSCs. Exogenous addition of either
      recombinant IGF-2 or MMP-1 could stimulate MSC migration. The correlation between
      IGF-2, MMP-1 expression, and MSC migration suggests that MMP-1 may play a role in
      regulating MSC migration via the IGF-2 signaling cascade. High concentrations of
      IGF binding proteins (IGFBPs) can inhibit IGF-stimulated functions by blocking
      its binding to its receptors and proteolysis of IGFBP is an important mechanism
      for the regulation of IGF signaling. We thus hypothesized that MMP-1 acts as an
      IGFBP2 proteinase, resulting in the cleavage of IGF-2/IGFBP2 complex and
      extracellular release of free IGF-2. Indeed, our results showed that conditioned
      media from highly migrating MSCs, which expressed high levels of MMP-1, cleaved
      the IGF-2/IGFBP2 complex. Taken together, these results showed that the MMP-1
      secreted by highly tumor-tropic MSCs cleaved IGF-2/IGFBP2 complex. Free IGF-2
      released from the complex may facilitate MSC migration toward tumor.

PMID- 29321954
TI  - A role for caspase-2 in sphingosine kinase 1 proteolysis in response to
      doxorubicin in breast cancer cells - implications for the CHK1-suppressed
      pathway.
AB  - Sphingosine kinase 1 (SK1) is a lipid kinase whose activity produces sphingosine
      1-phosphate, a prosurvival lipid associated with proliferation, angiogenesis, and
      invasion. SK1 overexpression has been observed in numerous cancers. Recent
      studies have demonstrated that SK1 proteolysis occurs downstream of the tumor
      suppressor p53 in response to several DNA-damaging agents. Moreover, loss of SK1
      in p53-knockout mice resulted in complete protection from thymic lymphoma,
      providing evidence that regulation of SK1 constitutes a major tumor suppressor
      function of p53. Given this profound phenotype, this study aimed to investigate
      the mechanism by which wild-type p53 regulates proteolysis of SK1 in response to
      the DNA-damaging agent doxorubicin in breast cancer cells. We find that p53
      mediated activation of caspase-2 was required for SK1 proteolysis and that
      caspase-2 activity significantly alters the levels of endogenous sphingolipids.
      As p53 is mutated in 50% of all cancers, we extended our studies to investigate
      whether SK1 is deregulated in the context of triple-negative breast cancer cells
      (TNBC) harboring a mutation in p53. Indeed, caspase-2 was not activated in these
      cells and SK1 was not degraded. Moreover, caspase-2 activation was recently shown
      to be downstream of the CHK1-suppressed pathway in p53-mutant cells, whereby
      inhibition of the cell cycle kinase CHK1 leads to caspase-2 activation and
      apoptosis. Indeed, knockdown and inhibition of CHK1 led to the loss of SK1 in p53
      mutant TNBC cells, providing evidence that SK1 may be the first identified
      effector of the CHK1-suppressed pathway.

PMID- 29321955
TI  - The central domain of UNC-45 chaperone inhibits the myosin power stroke.
AB  - The multidomain UNC-45B chaperone is crucial for the proper folding and function
      of sarcomeric myosin. We recently found that UNC-45B inhibits the translocation
      of actin by myosin. The main functions of the UCS and TPR domains are known but
      the role of the central domain remains obscure. Here, we show-using in vitro
      myosin motility and ATPase assays-that the central domain alone acts as an
      inhibitor of the myosin power stroke through a mechanism that allows ATP
      turnover. Hence, UNC-45B is a unique chaperone in which the TPR domain recruits
      Hsp90; the UCS domain possesses chaperone-like activities; and the central domain
      interacts with myosin and inhibits the actin translocation function of myosin. We
      hypothesize that the inhibitory function plays a critical role during the
      assembly of myofibrils under stress and during the sarcomere development process.

PMID- 29321956
TI  - An amebic protein disulfide isomerase (PDI) complements the yeast PDI1 mutation
      but is unable to support cell viability under ER or thermal stress.
AB  - In eukaryotic cells, protein disulfide isomerases (PDI) are oxidoreductases that
      catalyze the proper disulfide bond formation during protein folding. The
      pathobiology of the protozoan parasite Entamoeba histolytica, the causative agent
      of human amebiasis, depends on secretion of several virulence factors, such as
      pore-forming peptides and cysteine proteinases. Although the native conformation
      of these factors is stabilized by disulfide bonds, there is little information
      regarding the molecular machinery involved in the oxidative folding of amebic
      proteins. Whereas testing gene function in their physiological background would
      be the most suitable approach, we have taken advantage of the cellular benefits
      offered by the yeast Saccharomyces cerevisiae (as a model of eukaryotic cell) to
      examine the functional role of an amebic PDI (EhPDI). As the yeast PDI homolog is
      essential for cell viability, a functional complementation assay was carried out
      to test the ability of EhPDI to circumvent the lethal phenotype of a yeast PDI1
      mutant. Also, its proficiency under stressful conditions was explored by
      examining the survival outcome following endoplasmic reticulum (ER) stress
      induced by a reductant agent (DTT) or thermal stress promoted by a nonpermissive
      temperature (37  degrees C). Our results indicate that EhPDI is functionally
      active when physiological conditions are stable. Nonetheless, when conditions are
      stressful (e.g., by the accumulation of misfolded proteins in the ER
      compartment), its functionality is exceeded, suggesting an inability to prevent
      unfolding, suppress aggregation, or assist refolding of proteins. Despite the
      latter, our findings constitute the initial step toward determining the
      participation of EhPDI in cellular mechanisms related to protein homeostasis.

PMID- 29321957
TI  - High expression of PALB2 predicts poor prognosis in patients with advanced breast
      cancer.
AB  - PALB2 mutation is associated with increased breast cancer risk; however, PALB2
      mutation is rare in sporadic breast cancer cases and little is known about PALB2
      expression in breast cancer. Here, we evaluated the prognostic effects of PALB2
      with tissue microarray specimens of 117 female breast cancer patients, and
      determined the potential underlying mechanisms in cell models. In
      immunohistochemical analysis, we found increased expression of PALB2 in breast
      cancer tissues compared with the adjacent normal ductal epithelium (P < 0.001).
      Higher PALB2 scores were positively associated with histological grade and higher
      PALB2 expression was found in patients that were Her-2 negative compared with
      those that were positive (P < 0.05). Interestingly, higher expression of PALB2
      was significantly associated with poorer overall survival (P < 0.01) in patients
      with stage III or nearby lymph node metastasis (N1, N2 or N3). In vitro studies
      found that PALB2 may promote the migration and invasion of MDA-MB-231 cells
      through E-cadherin suppression and NF-kappaB activation. In conclusion, these
      results suggest that PALB2 expression levels may serve as a novel prognostic
      factor for breast cancer patients.

PMID- 29321958
TI  - Diagnostic value of strand-specific miRNA-101-3p and miRNA-101-5p for
      hepatocellular carcinoma and a bioinformatic analysis of their possible mechanism
      of action.
AB  - There is accumulating evidence that miRNA might serve as potential diagnostic and
      prognostic markers for various types of cancer. Hepatocellular carcinoma (HCC) is
      the most common type of malignant lesion but the significance of miRNAs in HCC
      remains largely unknown. The present study aimed to establish the diagnostic
      value of miR-101-3p/5p in HCC and then further investigate the prospective
      molecular mechanism via a bioinformatic analysis. First, the miR-101 expression
      profiles and parallel clinical parameters from 362 HCC patients and 50 adjacent
      non-HCC tissue samples were downloaded from The Cancer Genome Atlas (TCGA).
      Second, we aggregated all miR-101-3p/5p expression profiles collected from
      published literature and the Gene Expression Omnibus and TCGA databases.
      Subsequently, target genes of miR-101-3p and miR-101-5p were predicted by using
      the miRWalk database and then overlapped with the differentially expressed genes
      of HCC identified by natural language processing. Finally, bioinformatic analyses
      were conducted with the overlapping genes. The level of miR-101 was significantly
      lower in HCC tissues compared with adjacent non-HCC tissues (P < 0.001), and the
      area under the curve of the low miR-101 level for HCC diagnosis was 0.925 (P <
      0.001). The pooled summary receiver operator characteristic (SROC) of miR-101-3p
      was 0.86, and the combined SROC curve of miR-101-5p was 0.80. Bioinformatic
      analysis showed that the target genes of both miR-101-3p and miR-101-5p are
      involved in several pathways that are associated with HCC. The hub genes for miR
      101-3p and miR-101-5p were also found. Our results suggested that both miR-101-3p
      and miR-101-5p might be potential diagnostic markers in HCC, and that they exert
      their functions via targeting various prospective genes in the same pathways.

PMID- 29321959
TI  - Daily voluntary exercise enhances pilocarpine-induced saliva secretion and
      aquaporin 1 expression in rat submandibular glands.
AB  - Saliva-a water-based fluid containing electrolytes, immunoglobulins, and enzymes
      has many functions, including the protection and hydration of mucosal structures
      within the oral cavity and the initiation of digestion. Aquaporins (AQPs) are
      proteins that act as water channels through membranes. We have previously
      reported upregulation of the expression levels of AQP 1 and 5 in the
      submandibular glands (SMGs) in heat-acclimated rats. In this study, we
      investigated pilocarpine-induced saliva secretion and AQP expression in rats
      after voluntary exercise. Male, 10-week-old Wistar rats were initially maintained
      at an ambient temperature of 24  degrees C for 10 days and were then kept for 40
      days in cages either with a running wheel (exercise rats, n = 6) or with a locked
      wheel [control rats (CN), n = 6]. After the training period, the rats were
      anesthetized and pilocarpine, an M3 muscarinic receptor agonist, was
      intraperitoneally injected (0.5 mg.kg-1) to stimulate saliva secretion. Saliva
      was collected, and the SMGs were sampled and subjected to western blot, RT-PCR,
      and immunohistochemical analyses. Pilocarpine induced a greater amount of saliva
      in the exercised rats than in the CN. Expression levels of AQP1 mRNA and protein
      were significantly higher in SMGs of exercised rats than in those of the CN, but
      the expression of AQP5 was not affected by voluntary exercise. Voluntary exercise
      increased the expression of vascular endothelial growth factor (VEGF) and cluster
      of differentiation 31 (CD31), a marker for endothelial cells, in the SMGs.
      Voluntary exercise promoted pilocarpine-induced saliva secretion, probably via an
      increase in the expression level of AQP1 due to VEGF-induced CD31-positive
      angiogenesis in the SMG.

PMID- 29321960
TI  - The clinical value of miR-193a-3p in non-small cell lung cancer and its potential
      molecular mechanism explored in silico using RNA-sequencing and microarray data.
AB  - miR-193a-3p is a tumor-related miRNA playing an essential role in tumorigenesis
      and progression of non-small cell lung cancer (NSCLC). The objective of the
      present study was to investigate the relationship between miR-193a-3p expression
      and clinical value and to further explore the potential signaling of miR-193a-3p
      in the carcinogenesis of NSCLC. RNA-sequencing and microarray data were collected
      from the databases GEO, ArrayExpress and The Cancer Genome Atlas (TCGA).
      Furthermore, in silico assessments were performed to analyze the prospective
      pathways and networks of the target genes of miR-193a-3p. In total, 453 cases of
      NSCLC patients and 476 normal controls were included in blood samples, while 920
      cases of NSCLC patients and 406 normal controls were included in tissue samples.
      The pooled positive likelihood ratio, the pooled negative likelihood ratio and
      the pooled diagnostic odds ratio were calculated to reflect the diagnostic value
      of miR-193a-3p in blood and tissue samples. Moreover, the areas under the curve
      of the summary receiver operating characteristic curve of blood and tissue were
      0.64 and 0.79, respectively. In addition, we found a lower level of miR-193a in
      NSCLC tissues than in non-cancerous controls based on TCGA. A gene ontology (GO)
      enrichment analysis demonstrated that miR-193a-3p could be related to key
      signaling pathways in NSCLC. Also, several vital pathways were illustrated by
      KEGG. Lower expression of miR-193a-3p in tissue samples of NSCLC may be
      associated with tumorigenesis and be a predictor of deterioration of NSCLC
      patients, and pathway analysis revealed crucial signaling pathways correlated
      with the incidence and progress of NSCLC.

PMID- 29321961
TI  - Biophysical characterization of Atg11, a scaffold protein essential for selective
      autophagy in yeast.
AB  - Autophagy is an intracellular degradation system in which the formation of an
      autophagosome is a key event. In budding yeast, autophagosomes are generated from
      the preautophagosomal structure (PAS), in which Atg11 and Atg17 function as
      scaffolds essential for selective and nonselective types of autophagy,
      respectively. Structural studies have been extensively performed on Atg17, but
      not on Atg11, preventing us from understanding the selective type of the PAS.
      Here, we purified and characterized Atg11. Biophysical analyses, including
      analytical ultracentrifugation and CD, showed that Atg11 behaves as an elongated
      homodimer abundant in alpha-helices in solution. Moreover, truncation analyses
      suggested that Atg11 has a parallel coiled-coil architecture, in contrast to the
      antiparallel dimeric architecture of Atg17.

PMID- 29321962
TI  - Mutual influence of secondary and key drug-resistance mutations on catalytic
      properties and thermal stability of TEM-type beta-lactamases.
AB  - Highly mutable beta-lactamases are responsible for the ability of Gram-negative
      bacteria to resist beta-lactam antibiotics. Using site-directed mutagenesis
      technique, we have produced in vitro a number of recombinant analogs of naturally
      occurring TEM-type beta-lactamases, bearing the secondary substitution Q39K and
      key mutations related to the extended-spectrum (E104K, R164S) and inhibitor
      resistant (M69V) beta-lactamases. The mutation Q39K alone was found to be neutral
      and hardly affected the catalytic properties of beta-lactamases. However, in
      combination with the key mutations, this substitution resulted in decreased KM
      values towards hydrolysis of a chromogenic substrate, CENTA. The ability of
      enzymes to restore catalytic activity after exposure to elevated temperature has
      been examined. All double and triple mutants of beta-lactamase TEM-1 bearing the
      Q39K substitution showed lower thermal stability compared with the enzyme with
      Q39 intact. A sharp decrease in the stability was observed when Q39K was combined
      with E104K and M69V. The key R164S substitution demonstrated unusual ability to
      resist thermal inactivation. Computer analysis of the structure and molecular
      dynamics of beta-lactamase TEM-1 revealed a network of hydrogen bonds from the
      residues Q39 and K32, related to the N-terminal alpha-helix, towards the residues
      R244 and G236, located in the vicinity of the enzyme's catalytic site.
      Replacement of Q39 by lysine in combination with the key drug resistance
      mutations may be responsible for loss of protein thermal stability and elevated
      mobility of its secondary structure elements. This effect on the activity of beta
      lactamases can be used as a new potential target for inhibiting the enzyme.

PMID- 29321963
TI  - A critical role of hepatitis B virus polymerase in cirrhosis, hepatocellular
      carcinoma, and steatosis.
AB  - Hepatitis B is one of the most common infectious diseases in the world; more than
      350 million people are carriers of hepatitis B virus (HBV). Chronic HBV infection
      (CHB) leads to liver diseases such as cirrhosis, hepatocellular carcinoma (HCC),
      and steatosis. Despite its seriousness in terms of public health, the pathogenic
      mechanism of how CHB leads to liver diseases, especially cirrhosis and steatosis,
      remains unclear. We studied the role of HBV polymerase (HBp) reverse
      transcriptase (RT) activity in association with the pathogenesis of liver
      diseases in CHB by developing transgenic mice expressing HBp or the RT domain of
      HBp. Thorough pathological, serological, and histological analyses of the
      transgenic mice, as well as mechanistic studies, were conducted. All of the
      transgenic mice expressing RT in their livers developed early cirrhosis with
      steatosis by 18 months of age, and 10% developed HCC. The RT activity of HBp
      stimulates coordinated proapoptotic and proinflammatory responses involving the
      caspase-9, caspase-3, and caspase-1 pathways that might lead to the development
      of cirrhosis, HCC, and steatosis. The animal model described here should prove
      useful for elucidating the molecular events in the CHB-induced liver diseases.

PMID- 29321964
TI  - Introduction of H2C2-type zinc-binding residues into HIV-2 Vpr increases its
      expression level.
AB  - Human immunodeficiency virus type 2 has two structurally similar proteins, Vpx
      and Vpr. Vpx degrades the host anti-viral protein SAMHD1 and is expressed at high
      levels, while Vpr is responsible for cell cycle arrest and is expressed at much
      lower levels. We constructed a Vpr mutant with a high level of expression by
      replacing the amino acids HHCR/HHCH with a putative H2C2-type zinc-binding site
      that is carried by Vpx. Our finding suggests that during the evolution of Vpr and
      Vpx, zinc-binding likely became a mechanism for regulating their expression
      levels.

PMID- 29321965
TI  - Prognostic score for life expectancy evaluation of lung cancer patients after
      bone metastasis.
AB  - Background: This study identifies the overall survival status of lung cancer
      patients with bone metastasis and metastasis patterns. Poor prognostic factors
      were identified to develop a scoring system for estimating survival period after
      bone metastasis. Methods: A retrospective cohort analysis was performed at Chiang
      Mai University for the period January 1, 2006 and December 31, 2013. Time-to
      event analysis was performed to estimate survival rate. The primary end point was
      death related to lung cancer. Univariate and multivariate analysis of the
      prognostic variables was done using the Cox's regression model. The score was
      derived from the corresponding estimated regression coefficients of significantly
      poor prognostic factors. Results: A total of 505 lung cancer with bone metastasis
      patients were analyzed. Four hundred two cases (79.6%) were concurrent diagnosis
      and 103 (20.4%) were subsequent diagnosis. The median survival time of lung
      cancer after bone metastasis 148 days. Male gender and ECOG 3-4 were significant
      poor prognostic factors for lung cancer after bone metastasis, with hazard ratios
      of 1.42 (95% CI 1.17-1.73), and 1.30 (95% CI 1.06-1.60), respectively. Prognosis
      score was determined using the binary term present/not-present for those factors.
      The curve from prognostic score summations of 2, 1 and 0 presented a good
      discrimination of survival expectancy, showing an expected median survival time
      of approximately 109, 146, and 225 days, respectively. Conclusions: Prognostic
      score is a clinically simple and easy method for estimating life expectancy and
      for guiding interventions in bone metastasis of lung cancer.

PMID- 29321966
TI  - Small interfering RNA-mediated silencing of G-protein-coupled receptor 137
      inhibits growth of osteosarcoma cells.
AB  - Purpose: Osteosarcoma is the most widespread primary carcinoma in bones.
      Osteosarcoma cells are highly metastatic and frequently develop resistance to
      chemotherapy making this disease harder to treat. This identifies an urgent need
      of novel therapeutic strategies for osteosarcoma. G-Protein-coupled receptor 137
      (GPR137) is involved in several human cancers and may be a novel therapeutic
      target. Methods: The expression of GPR137 was assessed in one osteoblast and
      three human osteosarcoma cell lines via the quantitative real-time polymerase
      chain reaction and western blot assays. Stable GPR137 knockdown cell lines were
      established using an RNA interference lentivirus system. Viability, colony
      formation, and flow cytometry assays were performed to measure the effects of
      GPR137 depletion on cell growth. The underlying molecular mechanism was
      determined using signaling array analysis and western blot assays. Results:
      GPR137 expression was higher in the three human osteosarcoma cell lines, Saos-2,
      U2OS, and SW1353, than in osteoblast hFOB 1.19 cells. Lentivirus-mediated small
      interfering RNA targeting GPR137 successfully knocked down GPR137 mRNA and
      protein expression in both Saos-2 and U2OS cells. In the absence of GPR137, cell
      viability and colony formation ability were seriously impaired. The extent of
      apoptosis was also increased in both cell lines. Moreover, AMP-activated protein
      kinase alpha, proline-rich AKT substrate of 40 kDa, AKT, and extracellular signal
      regulated kinase phosphorylation levels were down-regulated in GPR137 knockdown
      cells. Conclusions: The results of this study highlight the crucial role of
      GPR137 in promoting osteosarcoma cell growth in vitro. GPR137 could serve as a
      potential therapeutic target against osteosarcoma.

PMID- 29321967
TI  - Teratoma as unusual cause of chest pain, hemoptysis and dyspnea in a young
      patient.
AB  - A 16-year-old girl presented with intermittent left chest pain and breathlessness
      on exertion for last 4 months with one episode of haemoptysis. There has been
      loss of appetite and weight loss of 4 kg over a period of 1 month. A chest
      radiograph revealed a large mass like opacity with pleural effusion in the left
      lung field. Computerized Tomography scanning (CT scanning) and Positron Emission
      Tomography/Computerized Tomography scanning (PET/CT scanning) demonstrated a 7 cm
      round, cystic lesion in the anterior mediastinum. Pleural fluid cytology did not
      show any malignant cell. The patient was referred to cardiothoracic department
      for thoracotomy and resection. Surgery was uncomplicated with rapid recovery.
      Histologic findings suggested mature teratoma components surrounded by oedematous
      pleura and pericardium with adjacent thymus and lung tissue.

PMID- 29321968
TI  - Achalasia with massive oesophageal dilation causing tracheomalacia and asthma
      symptoms.
AB  - Achalasia is an uncommon oesophageal motor disorder characterized by failure of
      relaxation of the lower oesophageal sphincter and muscle hypertrophy, resulting
      in a loss of peristalsis and a dilated oesophagus. Gastrointestinal symptoms are
      invariably present in all cases of achalasia observed in adults. We report a case
      of a 34 year-old female patient with long standing history of asthma-like
      symptoms, labelled as uncontrolled and steroid resistant asthma with no
      gastrointestinal manifestations. Thoracic CT scan revealed a massive oesophagus
      due to achalasia, which caused severe tracheomalacia as a result of tracheal
      compression. Her symptoms regressed completely after a laparoscopic Heller
      myotomy surgery intervention.

PMID- 29321969
TI  - The two-year progression of structural and functional cerebral MRI in amyotrophic
      lateral sclerosis.
AB  - MRI has emerged as one of several urgently needed candidate disease progression
      biomarkers for the neurodegenerative disorder amyotrophic lateral sclerosis
      (ALS), not least due to its unique ability to non-invasively assess structural
      and functional cerebral pathology. We sought to identify the extent of detectable
      change in cerebral MRI metrics over a more prolonged period. Analysis of multi
      modal MRI data was performed in a cohort of sixteen patients (13 ALS and 3 with
      primary lateral sclerosis) in whom it was possible to acquire six-monthly images
      over two years. Structural brain changes were assessed using voxel-based
      morphometry of grey matter and shape analysis of sub-cortical grey matter
      structures, tract-based spatial statistics of diffusion tensor imaging (DTI)
      metrics optimized for longitudinal analysis in the white matter, as well as whole
      brain voxel-wise statistics of DTI metrics. Changes in resting state functional
      MRI (rs-fMRI) were investigated via independent component and dual regression
      analyses of functional connectivity (FC), controlled for confounding effects of
      grey matter decline. Both linear changes with time and brain changes correlated
      with revised ALS functional rating score (ALSFRS-R) decline were studied.
      Widespread and progressive reductions in grey matter were observed in the
      precentral gyri and posterior cingulate cortex, as well as progressive local
      atrophy of the thalamus, caudate, and pallidum bilaterally, and right putamen,
      hippocampus and amygdala. The most prominent DTI tract-based changes were in the
      superior longitudinal fasciculi and corpus callosum. More widespread areas of DTI
      changes included the thalami and caudate nuclei, hippocampi and parahippocampal
      gyri, insular cortices, anterior and posterior cingulate gyri, frontal operculum
      and cerebellum. FC decreases were noted between the sensorimotor resting state
      network and the frontal pole, between a network comprising both thalami and an
      area in the visual cortex, in relation to both time from baseline and ALSFRS-R
      decline. FC increases between the left primary motor cortex and left fronto
      parietal network were seen for both statistical approaches. A longer period of
      follow-up, though necessarily involving more slowly-progressive cases,
      demonstrated widespread changes in both grey and white matter structural MRI
      measures. The mixed picture of regional decreases and increases in FC is
      compatible with compensatory change, in what should be viewed as a brain-based
      disease characterised by larger-scale disintegration of motor and frontal
      projection cerebral networks.

PMID- 29321970
TI  - DeepIED: An epileptic discharge detector for EEG-fMRI based on deep learning.
AB  - Presurgical evaluation that can precisely delineate the epileptogenic zone (EZ)
      is one important step for successful surgical resection treatment of refractory
      epilepsy patients. The noninvasive EEG-fMRI recording technique combined with
      general linear model (GLM) analysis is considered an important tool for
      estimating the EZ. However, the manual marking of interictal epileptic discharges
      (IEDs) needed in this analysis is challenging and time-consuming because the
      quality of the EEG recorded inside the scanner is greatly deteriorated compared
      to the usual EEG obtained outside the scanner. This is one of main impediments to
      the widespread use of EEG-fMRI in epilepsy. We propose a deep learning based semi
      automatic IED detector that can find the candidate IEDs in the EEG recorded
      inside the scanner which resemble sample IEDs marked in the EEG recorded outside
      the scanner. The manual marking burden is greatly reduced as the expert need only
      edit candidate IEDs. The model is trained on data from 30 patients. Validation of
      IEDs detection accuracy on another 37 consecutive patients shows our method can
      improve the median sensitivity from 50.0% for the previously proposed template
      based method to 84.2%, with false positive rate as 5 events/min. Reproducibility
      validation on 15 patients is applied to evaluate if our method can produce
      similar hemodynamic response maps compared with the manual marking ground truth
      results. We explore the concordance between the maximum hemodynamic response and
      the intracerebral EEG defined EZ and find that both methods produce similar
      percentage of concordance (76.9%, 10 out of 13 patients, electrode was absent in
      the maximum hemodynamic response in two patients). This tool will make EEG-fMRI
      analysis more practical for clinical usage.

PMID- 29321972
TI  - A case of urachal villous adenoma with high grade dysplasia focally bordering on
      adenocarcinoma in situ.

PMID- 29321971
TI  - Processing and regulation of negative emotions in anorexia nervosa: An fMRI
      study.
AB  - Theoretical models and recent advances in the treatment of anorexia nervosa (AN)
      have increasingly focused on the role of alterations in the processing and
      regulation of emotions. To date, however, our understanding of these changes is
      still limited and reports of emotional dysregulation in AN have been based
      largely on self-report data, and there is a relative lack of objective
      experimental evidence or neurobiological data. The current functional magnetic
      resonance imaging (fMRI) study investigated the hemodynamic correlates of passive
      viewing and voluntary downregulation of negative emotions by means of the
      reappraisal strategy detachment in AN patients. Detachment is regarded as
      adaptive regulation strategy associated with a reduction in emotion-related
      amygdala activity and increased recruitment of prefrontal brain regions
      associated with cognitive control processes. Emotion regulation efficacy was
      assessed via behavioral arousal ratings and fMRI activation elicited by an
      established experimental paradigm including negative images. Participants were
      instructed to either simply view emotional pictures or detach themselves from
      feelings triggered by the stimuli. The sample consisted of 36 predominantly
      adolescent female AN patients and a pairwise age-matched healthy control group.
      Behavioral and neuroimaging data analyses indicated a reduction of arousal and
      amygdala activity during the regulation condition for both patients and controls.
      However, compared with controls, individuals with AN showed increased activation
      in the amygdala as well as in the right dorsolateral prefrontal cortex (dlPFC)
      during the passive viewing of aversive compared with neutral pictures. These
      results extend previous findings indicative of altered processing of salient
      emotional stimuli in AN, but do not point to a general deficit in the voluntary
      regulation of negative emotions. Increased dlPFC activation in AN during passive
      viewing of negative stimuli is in line with the hypothesis that the disorder may
      be characterized by excessive self-control. Taken together, the data seem to
      suggest that reappraisal via detachment may be an effective strategy to reduce
      negative arousal for individuals with AN.

PMID- 29321973
TI  - A peripelvic renal cyst resulting in clinically symptomatic ureteropelvic
      junction obstruction.

PMID- 29321974
TI  - An uncommon association with sub-arachnoid hemorrhage in a young man.

PMID- 29321975
TI  - Unilateral renal forniceal rupture - A rare presentation of retroperitoneal
      fibrosis.

PMID- 29321976
TI  - Modified ex-vivo repair of distal renal artery aneurysm in a pediatric patient.

PMID- 29321977
TI  - Imidacloprid exposure cause the histopathological changes, activation of TNF
      alpha, iNOS, 8-OHdG biomarkers, and alteration of caspase 3, iNOS, CYP1A, MT1
      gene expression levels in common carp (Cyprinus carpio L.).
AB  - Imidacloprid (IMI) is a neonicotinoid that is widely used for the protection of
      crops and carnivores from insects and parasites, respectively. It is well known
      that imidacloprid exposure has a harmful effect on several organisms. However,
      there is little information about imidacloprid toxicity in aquatic animals,
      particularly fish. Thus, in the current study, we assessed the histopathological
      changes; activation of iNOS, 8-OHdG and TNF-alpha; and expression levels of
      caspase 3, iNOS, CYP1A and MT1 genes in the common carp exposed to imidacloprid.
      For this purpose, fish were exposed to either a low dose (140 mg/L) or a high
      dose (280 mg/L) of imidacloprid for 24 h, 48 h, 72 h and 96 h. After IMI
      exposure, we detected hyperplasia of secondary lamellar cells and mucous cell
      hyperplasia in the gills, as well as hydropic degeneration in hepatocytes and
      necrosis in the liver. Moreover, 8-OHdG, iNOS and TNF-alpha activation was found
      particularly in the gills and liver but also moderately in the brain.
      Transcriptional analysis showed that caspase 3 expression was altered low dose
      and high doses of IMI for 72 h and 96 h exposure (p < 0.05), iNOS expression was
      up-regulated with both low and high doses of IMI and in a time-dependent manner
      (p < 0.05, p < 0.01, p < 0.001), CYP1A expression was not significantly changed
      regardless of the dose of IMI and exposure time (p > 0.05) except with low and
      high doses of IMI for 96 h (p < 0.05), and lastly, MT1 gene expression was up
      regulated only in the brain with low doses of IMI for 96 h and high doses of IMI
      for 48 h, 72 h and 96 h exposure (p < 0.05, p < 0.01). Our results indicated that
      acute IMI exposure moderately induce apoptosis in the brain but caused severe
      histopathological lesions, inflammation, and oxidative stress in the gills,
      liver, and brain of the common carp.

PMID- 29321978
TI  - Toxicity of formulants and heavy metals in glyphosate-based herbicides and other
      pesticides.
AB  - The major pesticides of the world are glyphosate-based herbicides (GBH), and
      their toxicity is highly debated. To understand their mode of action, the
      comparative herbicidal and toxicological effects of glyphosate (G) alone and 14
      of its formulations were studied in this work, as a model for pesticides. GBH are
      mixtures of water, with commonly 36-48% G claimed as the active principle. As
      with other pesticides, 10-20% of GBH consist of chemical formulants. We
      previously identified these by mass spectrometry and found them to be mainly
      families of petroleum-based oxidized molecules, such as POEA, and other
      contaminants. We exposed plants and human cells to the components of
      formulations, both mixed and separately, and measured toxicity and human cellular
      endocrine disruption below the direct toxicity experimentally measured threshold.
      G was only slightly toxic on plants at the recommended dilutions in agriculture,
      in contrast with the general belief. In the short term, the strong herbicidal and
      toxic properties of its formulations were exerted by the POEA formulant family
      alone. The toxic effects and endocrine disrupting properties of the formulations
      were mostly due to the formulants and not to G. In this work, we also identified
      by mass spectrometry the heavy metals arsenic, chromium, cobalt, lead and nickel,
      which are known to be toxic and endocrine disruptors, as contaminants in 22
      pesticides, including 11 G-based ones. This could also explain some of the
      adverse effects of the pesticides. In in vivo chronic regulatory experiments that
      are used to establish the acceptable daily intakes of pesticides, G or other
      declared active ingredients in pesticides are assessed alone, without the
      formulants. Considering these new data, this assessment method appears
      insufficient to ensure safety. These results, taken together, shed a new light on
      the toxicity of these major herbicides and of pesticides in general.

PMID- 29321979
TI  - Improvement of Aspergillus flavus saponin hydrolase thermal stability and
      productivity via immobilization on a novel carrier based on sugarcane bagasse.
AB  - Soyasapogenol B (SB) is known to have many biological activities such as
      hepatoprotective, anti-inflammatory, anti-mutagenic, antiviral and anticancer
      activities. Enzymatic conversion of soyasaponins to SB was carried out using
      saponin hydrolase (SH) extracted from Aspergillus flavus. The partially purified
      enzyme was immobilized on different carriers by physical adsorption, covalent
      binding or entrapment. Among the investigated carriers, Eupergit C and sugarcane
      bagasse (SCB) activated by DIC and NHS were the most suitable two carriers for
      immobilization (the immobilized forms recovered 46.5 and 37.1% of the loaded
      enzyme activity, respectively). Under optimized immobilization conditions,
      immobilized SH on Eupergit C and on activated SBC recovered 87.7 and 83.3% of its
      original activity, respectively. Compared to free SH, immobilized SH on Eupergit
      C and on activated SCB showed higher optimum pH, activation energy, half-lives
      and lower deactivation constant rate. Also, their SB productivities were improved
      by 2.3- and 2.2-folds compared to free SH (87.7 and 83.3 vs. 37.5%,
      respectively). Hence, being SCB more sustainable and an inexpensive material, it
      can be considered a good alternative to Eupergit C as a support for SH
      immobilization. SH immobilization on industrially applicable and inexpensive
      carrier is necessary to improve SB yield and reduce its production cost. The
      chemical structure of SCB and the resulting cellulose derivatives were studied by
      ATR-IR spectroscopy. The thermal analysis technique was used to study the
      chemical treatment of SCB and coupling with the enzyme. This technique confirmed
      the removal of lignin and hemicellulose by chemical treatment of SCB.

PMID- 29321980
TI  - Transcriptome sequencing and de novo assembly in arecanut, Areca catechu L
      elucidates the secondary metabolite pathway genes.
AB  - Areca catechu L. belongs to the Arecaceae family which comprises many
      economically important palms. The palm is a source of alkaloids and carotenoids.
      The lack of ample genetic information in public databases has been a constraint
      for the genetic improvement of arecanut. To gain molecular insight into the palm,
      high throughput RNA sequencing and de novo assembly of arecanut leaf
      transcriptome was undertaken in the present study. A total 56,321,907 paired end
      reads of 101 bp length consisting of 11.343 Gb nucleotides were generated. De
      novo assembly resulted in 48,783 good quality transcripts, of which 67% of
      transcripts could be annotated against NCBI non - redundant database. The Gene
      Ontology (GO) analysis with UniProt database identified 9222 biological process,
      11268 molecular function and 7574 cellular components GO terms. Large scale
      expression profiling through Fragments per Kilobase per Million mapped reads
      (FPKM) showed major genes involved in different metabolic pathways of the plant.
      Metabolic pathway analysis of the assembled transcripts identified 124 plant
      related pathways. The transcripts related to carotenoid and alkaloid biosynthetic
      pathways had more number of reads and FPKM values suggesting higher expression of
      these genes. The arecanut transcript sequences generated in the study showed high
      similarity with coconut, oil palm and date palm sequences retrieved from public
      domains. We also identified 6853 genic SSR regions in the arecanut. The possible
      primers were designed for SSR detection and this would simplify the future
      efforts in genetic characterization of arecanut.

PMID- 29321981
TI  - Laparoscopic total pancreatectomy with islet autotransplantation for chronic
      pancreatitis.
AB  - Background: Pain from chronic pancreatitis can be debilitating and have far
      reaching personal and societal consequences. These consequences can include
      patient debilitation, worsening of comorbid conditions, narcotic dependence, and
      implications for health care policy. A variety of surgical procedures have shown
      limited efficacy for relieving pain in this cohort of patients, and a highly
      select subset may benefit from a total pancreatectomy (TP). While a brittle form
      of diabetes can result from TP alone, when combined with islet cell
      autotransplantation this procedural complication can be minimized. Further,
      utilizing a minimally invasive approach may be associated with decreased
      periprocedural pain and length of hospital stay. Methods: We describe our
      experience at a single high-volume center in the United States. We present our
      preferred preoperative evaluation, our updated operative techniques, and the
      standard perioperative care required following this complex laparoscopic
      procedure. Results: Between 2013 and 2015, there were 20 patients who underwent
      laparoscopic total pancreatectomy with islet autotransplantation (LTPIAT).
      Perioperative mortality was 0%. Conclusions: At a high volume pancreatic center
      with experienced laparoscopic pancreatic surgeons, LTPIAT is feasible and safe
      for the management of chronic pancreatitis refractory to prior medical and
      surgical therapies.

PMID- 29321982
TI  - Homeopathic Arnica from Boiron and post-operative bleeding in mastectomized women
      in Milan: Statistical flaws and bias to be addressed.
AB  - Image 1.

PMID- 29321983
TI  - Anti-paralytic medicinal plants - Review.
AB  - Paralysis is the loss of the ability of one or more muscles to move, due to
      disruption of signaling between the nervous system and muscles. The most common
      causes of paralysis are stroke, head injury, spinal cord injury (SCI) and
      multiple sclerosis. The search for cure of paralysis is yet to be found. Many
      ethnobotanical surveys have reported the use of medicinal plants by various
      ethnic communities in treating and curing paralysis. The present review discusses
      the use of medicinal plants in India for ameliorating and curing paralytic
      conditions, as well as discuses some of the important developments in future
      possible applications of medicinal plants in treatment of paralysis. This review
      reports the use of 37 medicinal plants for their application and cure of ailments
      related to paralysis. Out of the 37 plants documented, 11 plants have been
      reported for their ability to cure paralysis. However, the information on the
      documented plants were mostly found to be inadequate, requiring proper
      authentication with respect to their specificity, dosage, contradictions etc. It
      is found that despite the claims presented in many ethnobotanical surveys, the
      laboratory analysis of these plants remain untouched. It is believed that with
      deeper intervention on analysis of bioactive compounds present in these plants
      used by ethic traditional healers for paralysis, many potential therapeutic
      compounds can be isolated for this particular ailment in the near future.

PMID- 29321984
TI  - Effects of Bhramari Pranayama on health - A systematic review.
AB  - Pranayama, a branch of yoga practice is extremely beneficial to mankind in
      maintaining sound physical and mental health and this article aims to attain an
      insight on the studies conducted on the effectiveness of Bhramari Pranayama
      (Bhr.P) on health. The studies done until May 2016 were found using Medline,
      Embase, Google scholar and manual search. Studies conducted on the health
      effectiveness of Bhr.P specifically were included on the basis of prisma
      guidelines. The data were defined by their objectives, methodology, study
      setting, findings, interventions done and implications suggested in the study.
      Methodological Quality Rating Scale (MQRS) and Newcastle-Ottawa Scale (NOS) were
      used in reviewing and reporting results of the included studies. 6 studies
      satisfied the inclusion criteria; 2 studies were done on the cold pressor test,
      one on heart rate and BP, one on EEG changes, one each on the inhibitory response
      and tinnitus condition. In the included studies, the Bhr.P practices have shown
      para-sympathetic dominance. There are some encouraging effects of Bhr.P on
      various physiological systems. Methodological quality of the included studies was
      evaluated to be very low and none of them were RCTs. Yet the available studies
      are heterogeneous, dealing in different grounds and this heterogeneity serves as
      a resource for the limited scope of studies on Bhr.P. Therefore, further large
      scale, properly designed, randomized trials of Bhr.P on various systems have to
      be done to justify these effects efficiently.

PMID- 29321985
TI  - Traditional Persian Medicine and management of metabolic dysfunction in
      polycystic ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of
      reproductive age. Its cause is unknown and it remains the most enigmatic of
      reproductive disorders. The extant written documents of Traditional Persian
      Medicine (TPM) - with holistic approaches towards human health - contain remedies
      used for centuries. Before further experimental research on any of these
      treatments, it is appropriate to study current related scientific evidence on
      their possible pharmacological actions. This work aims to study PCOS and its
      treatments in TPM. To collect data from medieval medicinal texts, six of the most
      famous manuscripts of Persian medicine were studied. Medicinal treatments for a
      problem similar to PCOS were searched for in these books. The plants were listed
      and their authentications were confirmed in accordance with botanical books.
      PubMed and ScienceDirect databases were searched for related mechanisms of action
      or pharmacological activities of the medicinal plants reported. From numerous
      articles, the current work tried to cite the latest publications with regard to
      each reported plant and PCOS-related mechanisms of action. We studied herbal
      treatments recommended by ancient Persians to treat a condition called Habs-e
      tams, which had the same symptoms of PCOS. It could be concluded that ancient
      physicians not only wanted to treat the irregular menstrual cycle-which is the
      most obvious symptom of PCOS-but also their treatment options were aimed at
      ameliorating the related underlying metabolic dysfunctions. The recommended
      herbs, which have the most scientific proof for their related actions, can be
      studied further in experimental analyses.

PMID- 29321986
TI  - Traditional uses and pharmacological properties of Clerodendrum phytochemicals.
AB  - Clerodendrum is a genus of ca. 500 species in the family Lamiaceae and widely
      distributed throughout the whole world. Up to now, many species of this genus
      have been described in various indigenous systems of medicine and are used in
      preparation of folklore medicines for the treatment of various life-threatening
      diseases, and more than eleven species of the Clerodendrum genus have been very
      well studied for their chemical constituents and biological activities, and 283
      compounds, including monoterpene and its derivatives, sesquiterpene,
      diterpenoids, triterpenoids, flavonoid and flavonoid glycosides, phenylethanoid
      glycosides, steroids and steroid glycosides, cyclohexylethanoids, anthraquinones,
      cyanogenic glycosides, and others have been isolated and identified.
      Pharmacological studies have shown that these compounds and extracts from the
      Clerodendrum genus have extensive activities, such as anti-inflammatory and anti
      nociceptive, anti-oxidant, anti-hypertensive, anticancer, antimicrobial, anti
      diarrheal, hepatoprotective, hypoglycemic and hypolipidemic, memory enhancing and
      neuroprotective, and other activities. In this review, we attempt to highlight
      over phytochemical progress and list the phytoconstituents isolated from the
      genus Clerodendrum reported so far. The biological activities of this genus are
      also covered.

PMID- 29321987
TI  - Gelam honey attenuates ovalbumin-induced airway inflammation in a mice model of
      allergic asthma.
AB  - Allergic asthma is a chronic inflammatory disorder of the pulmonary airways.
      Gelam honey has been proven to possess anti-inflammatory property with great
      potential to treat an inflammatory condition. However, the effect of ingestion of
      Gelam honey on allergic asthma has never been studied. This study aimed to
      investigate the efficacy of Gelam honey on the histopathological changes in the
      lungs of a mice model of allergic asthma. Forty-two Balb/c mice were divided into
      seven groups: control, I, II, III, IV, V and VI group. All groups except the
      control were sensitized and challenged with ovalbumin. Mice in groups I, II, III,
      IV, and V were given honey at a dose of 10% (v/v), 40% (v/v) and 80% (v/v),
      dexamethasone 3 mg/kg, and phosphate buffered saline (vehicle) respectively,
      orally once a day for 5 days of the challenged period. Mice were sacrificed 24 h
      after the last OVA challenged and the lungs were evaluated for histopathological
      changes by light microscopy. All histopathological parameters such as epithelium
      thickness, the number of mast cell and mucus expression in Group III
      significantly improved when compared to Group VI except for subepithelial smooth
      muscle thickness (p < 0.05). In comparing Group III and IV, all the improvements
      in histopathological parameters were similar. Also, Gelam honey showed a
      significant (p < 0.05) reduction in inflammatory cell infiltration and beta
      hexosaminidase level in bronchoalveolar lavage fluid. In conclusion, we
      demonstrated that administration of high concentration of Gelam honey alleviates
      the histopathological changes of mice model of allergic asthma.

PMID- 29321988
TI  - Hypolipidemic effects of S-(+)-linalool and essential oil from Cinnamomum
      osmophloeum ct. linalool leaves in mice.
AB  - Cinnamomum osmophloeum ( tu rou gui) ct. linalool is one of the chemotypes of the
      indigenous cinnamon in Taiwan. S-(+)-linalool is the major constituent of leaf
      essential oil (LEO) of C. osmophloeum ct. linalool. This study aimed to
      investigate its physiological effects including body weight changes, blood
      biochemical values, and histopathological changes in mice. The mice were treated
      with LEO, S-(+)-linalool, and R-(-)-linalool. Results demonstrated similar
      physiological changes in mice treated with LEO and S-(+)-linalool, but
      significantly different effects in the body weight, TG, TC and blood glucose of R
      (-)-linalool group. S-(+)-linalool-treated mice gained less weight and had
      significant decrease in blood triglyceride levels. No histopathological changes
      were observed in livers, kidneys, and spleens of S-(+)-linalool-treated mice.
      Furthermore, there were no significant differences in aspartate aminotransferase
      (AST) and alanine aminotransferase (ALT) levels between S-(+)-linalool-treated
      mice and the control group. In addition, LEO and S-(+)-linalool significantly
      inhibited lipid accumulation through down-regulation of 3T3-L1 adipocyte
      differentiation. Taken together, the results show that LEO and S-(+)-linalool
      from C. osmophloeum ct. linalool can contribute to body weight management without
      harmful side effects.

PMID- 29321989
TI  - Antidepressant-like effects of Gan-Mai-Dazao-Tang via monoamine regulatory
      pathways on forced swimming test in rats.
AB  - Depression is a highly prevalent and recurrent mental disorder that impacts all
      aspects of human life. Undesirable effects of the antidepressant drugs led to the
      development of complementary and alternative therapies. Gan-Mai-Da-Zao-Tang (,
      gan mai da zao tang) is a traditional herbal formula commonly used for the
      treatment of depression, but lack of scientific proof on its mechanism. It
      consisted of Glycyrrhiza uralensis Fisch. (licorice), Triticum aestivum L.
      (wheat) and Zizphus jujuba Mill. (jujube). The objective of this study is to
      investigate the antidepressant effects of Gan-Mai-Dazao-Tang and its ingredients
      in rats exposed to forced swimming test (FST). The 72 of male Nerl: Wistar rats
      (8 weeks old) were randomized into control (10 mL/kg bw H2O), licorice (0.4 g/kg
      bw), wheat (1.6 g/kg bw), jujube (0.5 g/kg bw), Gan-Mai-Da-Zao-Tang (2.5 g/kg bw
      of licorice: wheat: jujube in ratio of 5:20:6) and Prozac (18 mg/kg bw) groups.
      Samples were administered by oral gavage for 21 days. FST was performed on 21st
      day, with 15 min for pretest followed by 5 min for real test. Then, the animals
      were sacrificed and brain tissues were collected for monoamines analyses. The Gan
      Mai-Da-Zao-Tang (LWJ) showed significantly down-regulation of immobility time,
      3,4-dihydroxyphenylacetic acid (DOPAC) and DOPAC/dopamine (DA) turnover rates,
      and also enhanced the concentration of serotonin (5-HT) and DA in brain tissues,
      as compared with the control. The LWJ stated the potent antidepressant-like
      effect by modulating these monoamines concentration, while the licorice, wheat
      and jujube did not reported significant results as compared with control group.
      The positive control (Prozac) was noted with significantly reduction in body
      weight and appetite. In conclusion, the antidepressant-like effects of LWJ might
      be mediated by the regulation of monoamine neurotransmitters. Thus, it could
      beneficial in depression treatment as a complementary approach.

PMID- 29321990
TI  - In vitro antioxidant activities of root extract of Asparagus racemosus Linn.
AB  - Objective: The purpose of the study is to investigate potential of antioxidant
      property of ethanolic root extract of Asparagus racemosus Linn (EEAR). Methods:
      In vitro evaluation antioxidant property of EEAR was done using various methods
      like DPPH scavenging activity, hydroxyl radical scavenging activity, and nitric
      oxide scavenging activity. HPTLC fingerprint analysis was performed for
      qualitative determination of possible number of components from the ethanolic
      extract. Acute toxicity study was performed in Wistar rat and an OECD guideline
      423 was followed. Results: The yield value was found 0.96% from EEAR. A
      concentration of 468.57 +/- 3.002 MUg/ml of probable antioxidant material from
      EEAR was required to scavenge 50% of DPPH. The IC50 value of EEAR were found to
      be 508.17 +/- 7.37 MUg and 416.57 +/- 5.08 MUg when determined by hydroxyl
      radical and nitric oxide scavenging assay respectively. The reducing powers of
      EEAR was 0.295 +/- 0.0037 at 125 MUg/ml and increased to 0.934 +/- 0.0005 at 500
      MUg/ml. HPTLC fingerprint data supports several basic informations like
      isolation, purification, quality evaluation and standardization. No sign of
      toxicity was observed after treated with 2000 mg/kg of EEAR. Conclusion: The
      obtained data highlight the potential role of EEAR as a source of natural
      antioxidants.

PMID- 29321991
TI  - Buddleja globosa (matico) prevents collagen-induced platelet activation by
      decreasing phospholipase C-gamma 2 and protein kinase C phosphorylation
      signaling.
AB  - Platelets play a key role in thrombosis and cardiovascular diseases. Medicinal
      plants could be one of the most important factors that influence risks for
      platelet activation. Buddleja globosa (known as "matico") is a medicinal plant
      with many biological activities. The high content of polyphenols suggest that
      matico could have antiplatelet activity. The present study was aimed at
      evaluating mechanisms of antiplatelet action of an extract of matico. We
      demonstrated that matico extract at low concentrations and in a concentration
      dependent manner (0.05-1 mg/mL) was a potent inhibitor of platelet aggregation in
      response to collagen, convulsion and ADP (IC50 values was 61 MUg/mL, 72 MUg/mL
      and 290 MUg/mL, respectively). In this sense matico extract exerted the greatest
      antiaggregant activity induced by collagen. Similarly, matico showed a decrease
      in % of positive platelet for P-selectina (vehicle, 0.01, 0.05, 0.1, 0.5 and 1
      mg/mL were 32 +/- 2%, 29 +/- 2 (p < 0.05), 19 +/- 1 (p < 0.01), 15 +/- 2 (p <
      0.01), 10 +/- 1% (p < 0.01) and 7 +/- 2% (p < 0.01), respectively) and PAC-1
      binding (vehicle, 0.01, 0.05, 0.1, 0.5 and 1 mg/mL were 59 +/- 1, 58 +/- 3 (n.s),
      55 +/- 2 (p < 0.05), 50 +/- 2 (p < 0.01), 38 +/- 1 (p < 0.01), 36 +/- 2 (p <
      0.01). The cellular mechanism for the antiplatelet activity of matico might be
      mediated by the inhibition of phospholipase C-gamma 2 and protein kinase C
      phosphorylation. This beneficial property of matico may be of importance in
      thrombosis, in which platelet activation and aggregation are important
      determinants of thrombus initiation and development, and may contribute to the
      beneficial effects of matico intake in the prevention of cardiovascular diseases.

PMID- 29321992
TI  - Alterations of haemodynamic parameters in spontaneously hypertensive rats by
      Aristolochia ringens Vahl. (Aristolochiaceae).
AB  - Aristolochia ringens Vahl. (Aristolochiaceae (AR); ma dou ling) is used
      traditionally in Nigeria for the management of various disorders including
      oedema. Preliminary investigation revealed its modulatory effect on the
      cardiovascular system. This study was aimed at investigating the effect of the
      aqueous root extract of A. ringens (AR) on haemodynamic parameters of
      spontaneously hypertensive rats (SHRs). The effect of oral subacute (21 days) and
      intravenous acute exposure of SHRs to the extract were assessed using tail cuff
      and carotid artery canulation methods respectively. In the latter, the effect of
      chloroform, butanol and aqueous fractions of AR were also evaluated. The extract
      significantly reduced systolic and diastolic blood pressures in SHRs, with peak
      reductions of 20.3% and 26.7% respectively at 50 mg/kg by the 21st day of oral
      subacute exposure. Upon intravenous exposure, AR (50 mg/kg) reduced systolic and
      diastolic blood pressure by as much as 53.4 +/- 2.2 and 49.2 +/- 2.8 mmHg
      respectively. A dose-dependent reduction in heart rate, significant at 25 and 50
      mg/kg was also observed. Hexamethonium (20 mg/kg) and atropine (1 mg/kg)
      inhibited the extract's reduction of systolic blood pressure, diastolic blood
      pressure and heart rate significantly. The extract's butanol fraction produced
      the greatest systolic and diastolic blood pressures reduction of 67.0 +/- 3.8 and
      68.4 mmHg respectively at 25 mg/kg and heart rate reduction of 40 +/- 7 beats per
      minute at 50 mg/kg. HPLC analysis revealed the presence of 4-hydroxybenzoic acid
      and quercetin in AR. The extract's alterations of haemodynamic parameters in this
      study show that it has hypotensive effect on spontaneously hypertensive rats.

PMID- 29321993
TI  - Sansoninto, a traditional herbal medicine, ameliorates behavioral abnormalities
      and down-regulation of early growth response-1 expression in mice exposed to
      social isolation stress.
AB  - Social isolation (SI) mice exhibit behavioral abnormalities such as impairments
      of sociability- and attention-like behaviors, offering an animal model of
      neurodevelopmental disorders such as attention-deficit/hyperactivity disorder
      (ADHD). This study aimed to identify the effects of Sansoninto (SST; suan zao ren
      tang) on the psychiatric symptoms related to ADHD using SI mice. Four-week-old
      mice were socially isolated during the experimental period, and SST
      administration (800 or 2400 mg/kg, p.o.) was started at 2 weeks after starting
      SI. SST ameliorated SI-induced impairments of sociability- and attention-like
      behaviors in a dose-dependent manner, and tended to ameliorate contextual- and
      auditory-dependent fear memory deficit. Moreover, the expression level of Egr-1
      was down-regulated by SI stress, and was restored by a high dose of SST. These
      findings suggest that SST is useful for improvement of psychiatric disorders such
      as ADHD.

PMID- 29321994
TI  - The effect of ethanolic extract of Thymus kotschyanus on cancer cell growth in
      vitro and depression-like behavior in the mouse.
AB  - Cancer and depression are known as two of the most debilitating disease and
      disorder increasing evidence suggest an urgent need for new therapeutic agents
      with lower toxicity and high efficacy. Some Thyme species extracts have
      remarkably been shown to positively affect depression and cancer cells. In the
      present study, we investigated the effect of Thymus kotschyanus on depression and
      cancer cells. To this end, in experiment 1, NMRI mice were treated orally with
      the ethanolic extract of T. kotschyanus (50, 150 and 250 mg/ml) for seven days
      and then depression-like behavior was measured by Forced Swim Test (FST) and Tail
      Suspension Test (TST). In experiment 2, the pharmacological effect of the extract
      on the lung (A549) and cervical (Hela) cancer cell lines was also evaluated by
      MTT (3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide) in various
      concentration_(10, 5, 2.5, 1.25, 0.63, 0.31, 0.15 and 0.08 mg/ml). The results
      indicated that T. kotschyanus extract treatment (150 and 250 mg/kg) decreased
      depression-like behavior in the FST and TST tests in adult mice. Moreover, the
      treatment inhibited cancer cell growth and viability in a dose and time-dependent
      manner. Collectively these findings suggest that T. kotschyanus have
      antidepressant and anticancer effects.

PMID- 29321995
TI  - Anticonvulsant effect of ethanolic extract of Cyperus articulatus L. leaves on
      pentylenetetrazol induced seizure in mice.
AB  - Cyperus articulatus (CA) rhizomes have demonstrated different properties on
      nervous system. However, the leaves still have not studied to treat epilepsy. The
      aim of this study was to determine the effect of CA ethanolic extract on
      pentylenetetrazol (PTZ) induced seizures in mice as well as measuring its
      antioxidant activity in vivo and in vitro. Mice were divided into five groups:
      (1) control (PTZ 80 mg/kg; i.p.), (2) PTZ-Diazepam (1 mg/kg; i.p.), (3-5) PTZ-CA
      50, PTZ-CA 150 and PTZ-CA 300 (50, 150 and 300 mg/kg of CA extract, 30 min prior
      to each PTZ injection). The PTZ-CA 150 group showed lower seizure scores (P <
      0.01), latency (P < 0.01), frequency (P < 0.01) and duration (P < 0.01) than
      control group. The antioxidant activity of CA extract scavenged DPPH radical
      showed IC 50 = 16.9 +/- 0.1 MUg/mL and TEAC = 2.28 +/- 0.08, mmol trolox/g of
      extract, the content of gamma amino butyric acid (GABA) and malondialdehyde (MDA)
      were significantly high (P < 0.01) at dose of 150 mg/kg (82 +/- 1.2 ng/g tissue;
      1.0 +/- 2.2 mol/g tissue, respectively). The present research demonstrated that
      CA extract possesses a potential effect to prevent PTZ induced seizures,
      antioxidant activity in addition to increase GABA levels.

PMID- 29321996
TI  - Comparative evaluation of antimicrobial and antioxidant potential of ethanolic
      extract and its fractions of bark and leaves of Terminalia arjuna from north
      western Himalayas, India.
AB  - The present study was aimed to evaluate the antimicrobial and antioxidant
      potential of ethanolic extract and its different solvent fractions (chloroform,
      ethyl acetate, n-butanol and aqueous fraction) of bark and leaves of Terminalia
      arjuna. The antimicrobial activity was determined by disc diffusion and minimum
      inhibitory concentration (MIC) methods against six bacterial stains. The
      antioxidant activity was evaluated by using DPPH, FRAP and Nitric oxide (NO)
      scavenging assay. The total phenolics and flavonoid content were found to be
      higher in n-butanolic fraction of bark (294.6 +/- 8.1 mg/g GAE and 168.6 +/- 12.3
      mg/g RE, respectively) and leaves (203.7 +/- 7.0 mg/g GAE and 144.8 +/- 11.1 mg/g
      RE, respectively). The maximum antimicrobial activity was shown by n-butanolic
      fraction of bark and leaves. The zone of inhibition of 15.0 +/- 0.7 mm, 15.5 +/-
      0.7 mm, 15.0 +/- 1.5 mm, 15.5 +/- 0.7 mm, 15.0 +/- 0.7 mm, 15.0 +/- 0.7 mm was
      observed against Bacillus subtilis, Staphylococcus aureus, Eschericia coli,
      Klebsiella pneumoniae, Pseudomonas aeruginosa and Salmonella typhi respectively.
      In case of leaves extract, zone of inhibition of 13.5 +/- 0.7 mm, 16.5 +/- 0.7
      mm, 14.0 +/- 0.5 mm, 15.0 +/- 0.5 mm, 13.5 +/- 0.7 mm, 14.0 +/- 0.7 mm was
      observed against B. subtilis, S. aureus, E. coli, K. pneumoniae, P. aeruginosa,
      S. typhi, respectively. The n-butanol fraction of bark [IC50-4.1 MUg/ml (DPPH),
      21.0 MUM (FRAP), 3.3 MUg/ml (NO)] and leaves [IC50-4.8 MUg/ml (DPPH), 28.9 MUM
      (FRAP), 3.2 MUg/ml (NO)] showed more antioxidant potential as compared to that of
      crude ethanolic extract, ethyl acetate fraction, chloroform fraction, aqueous
      fraction and even ascorbic acid. These results clearly indicated comparative
      antioxidant potential and antimicrobial activity in extracts of bark and leaves
      of T. arjuna.

PMID- 29321997
TI  - Ascertainment of pharmacological activities of Allamanda neriifolia Hook and
      Aegialitis rotundifolia Roxb used in Bangladesh: An in vitro study.
AB  - The present study was cherished to investigate in vitro thrombolytic, membrane
      stabilizing and antibacterial activities of Allamanda neriifolia and Aegialitis
      rotundifolia. Different types methanolic extracts of these two medicinal plants
      were tested for determining membrane stabilizing activity at a hypotonic solution
      and heat induce condition by comparing with reference standard acetyl salicylic
      acid (0.10 mg/mL), where thrombolytic activity assessment was done by employing
      Streptokinase as standard drug. Finally, antibacterial activity was performed
      against Staphylococcus aureus as a Gram-positive (+ve) and Salmonella typhi,
      Escherichia coli and Pseudomonas aeruginosa as Gram negative (-ve) bacteria by
      using disc diffusion method. In case of membrane stabilizing studies, crude
      methanolic extracts of A. neriifolia at 10 mg/ml concentration, more importantly,
      showed 45.80% & 23.52% whereas 10 mg/ml concentration of A. rotundifolia more
      significantly (p < 0.01) produced 38.40% and 27.04% inhibition of hemolysis for
      both experimental conditions. Dose-dependently increased activity was found in
      the thrombolytic study where 10 mg/ml concentration of both A. neriifolia and A.
      rotundifolia more significantly (p < 0.01) showed 41.91% and 32.76% lysis of clot
      respectively by in vitro clot lysis assay method. Crude methanolic extracts of A.
      rotundifolia did not show any suitable antibacterial property against the test
      bacteria. However, the gram positive (+ve) bacteria also seemed resistant against
      A. neriifolia extract but this crude methanolic extracts was found to generate
      moderate antibacterial action against gram-negative (-ve) bacteria. The obtained
      results confirmed the presence of thrombolytic, membrane stabilizing activity for
      both plant extract along with moderate antibacterial activity for A. neriifolia.

PMID- 29321998
TI  - Effectiveness of two different herbal toothpaste formulations in the reduction of
      plaque and gingival inflammation in patients with established gingivitis - A
      randomized controlled trial.
AB  - Background: Plant based toothpastes have received great attention in reducing
      gingival inflammation. Studies show contrasting results regarding the
      effectiveness of these toothpastes. In the present study, the effectiveness of
      two herbal tooth paste formulations in the reduction of plaque and gingival
      inflammation was assessed. Nicotine content in the toothpastes was assessed using
      GCMS. Material and methods: 50 patients with established gingivitis were included
      in the study. The subjects were randomly assigned to either the test
      (Parodontax(r)) or the control (Colgate(r) herbal) group. There were 5 drop outs
      in the study in the control group after baseline examination. No prophylaxis was
      undertaken prior to commencement of the study, and no attempt was made to modify
      the participant's oral hygiene habits. A brief case history was recorded at
      baseline. The Turesky (1970) modification of the Quigley, Hein (1962) Plaque
      index (PI), the Loe and Silness (1963) Gingival Index (GI). Unstimulated salivary
      samples were collected at baseline and 30th day and the pH was measured using a
      salivary pH meter (CL-51B; Systronics New Delhi, India).Comparisons (intergroup
      and intragroup) were analysed by the t-test. Groups were also compared regarding
      age by means of t test, and association between group and sex was verified by
      means of the chi-square test. All statistical tests employed a level of
      significance of alpha = 0.05. There were reports of presence of nicotine and its
      derivatives in herbal toothpaste after the study was nearing completion. Hence we
      assessed for the presence of nicotine in both the toothpaste using the methods
      described by Aggarwal et al.24. Results: When the two groups (test and control
      groups) were evaluated, after 30 days, the test group presented an average 21.08%
      reduction in plaque and the control group showed 31.85% reduction in plaque
      scores. The mean reduction in gingival index (GI) scores was 25.92% and 19.14% in
      the test and control groups respectively. There was no significant difference
      between the groups in GI, PI and salivary pH levels. There was no evidence of
      nicotine or related compounds in both the tooth paste. Conclusion: Both herbal
      based dentifrices reduce plaque levels and gingival inflammation. But, it did not
      alter the pH of the saliva. However, there were no additional benefits of the
      Parodontax(r) toothpaste over Colgate(r) Herbal toothpaste. There was no evidence
      of nicotine or related compounds in both herbal toothpaste.

PMID- 29321999
TI  - Antioxidant and hepatoprotective effects of Capparis spinosa L. fractions and
      Quercetin on tert-butyl hydroperoxide- induced acute liver damage in mice.
AB  - The present study investigates the antioxidant and hepatoprotective effects of
      Capparis spinosa L. and Quercetin in tert-butyl hydroperoxide (t-BHP) induced
      acute liver damage. Different fractions of C. spinosa were examined for total
      phenolic content and antioxidant property. Among these fractions, hydroalcoholic
      extract was used to assess the hepatoprotective effect in tert-butyl
      hydroperoxide (t-BHP) induced hepatotoxicity model by determining serum
      biochemical markers, sleeping time and antioxidant assay such as reduced
      glutathione (GSH) as well as histopathological examination of liver tissues. The
      total phenolic and Quercetin contents of hydroalcoholic fraction were
      significantly higher than other fractions. It also showed high antioxidant
      activity. Pretreatment with hydroalcoholic fraction at the dose of 400 mg/kg and
      Quercetin at the dose of 20 mg/kg showed liver protection against t-BHP induced
      hepatic injury, as it was evident by a significant decrease in serum enzymes
      marker, sleeping time and MDA and an increase in the GSH, SOD and CAT activities
      confirmed by pathology tests. The final results ascertained the hepatoprotective
      and antioxidant effects of C. spinosa and Quercetin in a dose-dependent manner.
      Moreover, this study suggests that possible mechanism of this protection may be
      associated with its property of scavenging free radicals which may be due to the
      presence of phenolic compounds.

PMID- 29322000
TI  - Effects of cinnamon supplementation on antioxidant status and serum lipids in
      women with polycystic ovary syndrome.
AB  - Background: The objectives of study were to investigate the effects of cinnamon
      supplementation on antioxidant status and serum lipids in women with polycystic
      ovary syndrome (PCOS). Methods: This double-blind randomized controlled clinical
      trial was conducted on 84 overweight or obese PCOS patients; aged 20-38 years.
      Subjects in cinnamon (n = 42) and placebo (n = 42) groups were given 3 cinnamon
      capsules (each one contained 500 mg cinnamon) or placebo daily for 8 weeks.
      Fasting blood samples, anthropometric measurements and dietary intake data were
      gathered at the beginning and at the end of the study. Independent t test, paired
      t test and analysis of covariance were used to analyze of data. Results: Cinnamon
      significantly increased serum total antioxidant capacity (P = 0.005).
      Malondialdehyde was significantly decreased compared with placebo (P = 0.014).
      Cinnamon supplementation significantly improved serum level of total cholesterol,
      low-density lipoprotein cholesterol and high-density lipoprotein cholesterol (all
      P < 0.05). No significant effect was detected on serum triglyceride level.
      Conclusions: Cinnamon supplementation improved antioxidant status and serum lipid
      profile in women with PCOS and may be applicable for reducing PCOS risk factors.

PMID- 29322001
TI  - Evaluation of the antidiabetic property of aqueous leaves extract of Zanthoxylum
      armatum DC. using in vivo and in vitro approaches.
AB  - The present study was designed to evaluate the antidiabetic potential of the
      aqueous leaves extract of Zanthoxylum armatum DC. leaves using in vivo and in
      vitro approaches. For in vivo studies, blood glucose level was monitored at
      different intervals after administration of varying doses of the extract for its
      hypoglycemic (100-6000 mg/kg b.w.) and antihyperglycemic (250 mg/kg b.w.) effect
      in normoglycemic and diabetic mice. In vitro enzymatic inhibition activity was
      tested against alpha-amylase, alpha- and beta-glucosidase and lipase.
      Additionally hydroxyl radical, hydrogen peroxide scavenging assay and
      phytochemical screening were also performed. Element analysis of the plant was
      studied by Atomic Absorption Spectrometry (AAS) and Inductively Coupled Plasma
      Atomic Emission Spectrometer (ICP-AES). The plant extract showed significant
      hypoglycemic and antihyperglycemic effect in normoglycemic and diabetic mice. The
      IC50 values of extract for alpha-amylase, beta-glucosidase, lipase, hydroxyl
      radical scavenging activity, hydrogen peroxide scavenging activity were 7.40
      mg/ml, 0.30 mg/ml, 8.35 mg/ml, 3.25 mg/ml, 9.62 mg/ml respectively and the
      percentage of inhibition for alpha-glucosidase was 79.82% at 0.8 mg/ml. In vitro
      studies were compared with their respective standards. Elemental analysis
      revealed the presence of essential elements such as Mg, V, Fe, Cr, Zn, Cu, Mo,
      Mn, K, Ca, P and Sr which are all known to play a role in regulating blood
      glucose. The results demonstrate that Z. armatum aqueous leaves extract possess
      antidiabetic property in both in vivo and in vitro condition.

PMID- 29322002
TI  - Complementary and alternative medicine use in thalassemia patients in Shiraz,
      southern Iran: A cross-sectional study.
AB  - This study aimed to determine the frequency and pattern of complementary and
      alternative medicine (CAM) use in thalassemia patients in south of Iran. The
      survey was done using a validated questionnaire which was distributed among 122
      thalassemia patients. Only 108 questionnaires were completed and turned back
      (response rate 88.5%). Patients referred to an outpatient thalassemia clinic in
      Shiraz, southern Iran for blood transfusion. The mean age of the patients was
      22.9 +/- 7.9 years (range 4-45 years) with female/male ratio 1.84. Seventy four
      (68.5%) of the responders used CAM at least once during their life, and about
      half of them used it concurrently with their conventional treatments. The most
      reported CAM product was mint juice (50%). The most common reason of CAM use was
      increased general health. The most common information source about CAM was
      physicians who were the most trusted source as well. CAM is frequently being used
      in thalassemia patients to ensure their sense of well-being and help them
      overcome the complications of their illnesses.

PMID- 29322003
TI  - Preliminary phytochemical analysis and in vivo evaluation of antipyretic effects
      of hydro-methanolic extract of Cleome scaposa leaves.
AB  - Cleome scaposa has been associated with the prevention of many diseases as fever,
      abdominal complaints and cancer. But its antipyretic effect is not reported so
      far. The aim of this study was to assess the efficacy of C. scaposa in reducing
      temperature in Baker's yeast-induced fever model of rabbits. Rabbits were
      randomized into 4 groups (n = 24). Fever was induced in by Saccharomyces
      cerevisae (3 mL/kg of 10% suspension subcutaneous) in all study groups.
      Afterward, group 1, 2, 3 and 4 were orally administered with paracetamol 150
      mg/kg b. wt., distilled water, C. scaposa 250 and 500 mg/kg b. wt. respectively.
      500 mg/kg dosage was selected after dose fixation study. The standard control was
      paracetamol. Rectal temperature was recorded with the help of a digital
      thermometer. ANOVA followed by post hoc test was applied for statistical analysis
      of results. Results of the study indicate that C. scaposa possesses antipyretic
      activity comparable to that of standard drug paracetamol as it exhibited
      comparable antipyretic potential against baker's yeast-induced fever in rabbits.
      This study confirms the traditional use of C. scaposa in fever. So, it can be an
      alternative therapeutic choice in fever. However, specific constituents
      responsible for its antipyretic activity should be evaluated.

PMID- 29322004
TI  - Thoughts modulate the expression of inflammatory genes and may improve the
      coronary blood flow in patients after a myocardial infarction.
AB  - Background: Mental stress is one of the main risk factors for cardiovascular
      disease. Meditation and music listening are two techniques that are able to
      counteract it through the activation of specific brain areas, eliciting the so
      called Relaxing Response (RR). Epidemiological evidence reveals that the RR
      practice has a beneficial prognostic impact on patients after myocardial
      infarction. We aimed to study the possible molecular mechanisms of RR underlying
      these findings. Methods: We enrolled 30 consecutive patients after myocardial
      infarction and 10 healthy controls. 10 patients were taught to meditate, 10 to
      appreciate music and 10 did not carry out any intervention and served as
      controls. After training, and after 60 days of RR practice, we studied the
      individual variations, before and after the relaxation sessions, of the vital
      signs, the electrocardiographic and echocardiographic parameters along with
      coronary flow reserve (CFR) and the carotid's intima media thickness (IMT). Neuro
      endocrine-immune (NEI) messengers and the expression of inflammatory genes (p53,
      Nuclear factor Kappa B (NfKB), and toll like receptor 4 (TLR4)) in circulating
      peripheral blood mononuclear cells were also all observed. Results: The RR
      results in a reduction of NEI molecules (p < 0.05) and oxidative stress (p <
      0.001). The expression of the genes p53, NFkB and TLR4 is reduced after the RR
      and also at 60 days (p < 0.001). The CFR increases with the relaxation (p <
      0.001) and the IMT regressed significantly (p < 0.001) after 6 months of RR
      practice. Conclusions: The RR helps to advantageously modulate the expression of
      inflammatory genes through a cascade of NEI messengers improving, over time,
      microvascular function and the arteriosclerotic process.

PMID- 29322005
TI  - Self microemulsifying formulation of Lagerstroemia speciosa against chemically
      induced hepatotoxicity.
AB  - Self microemulsifying formulation is an approach used for enhancing the
      bioavailability of poorly soluble molecules due to their lipidic nature and small
      particle size. The objective of the present study was to evaluate the
      hepatoprotective activity of poorly soluble hydroxy- and polyhydroxy-organic
      phytomolecules rich Lagerstroemia speciosa leaves extract in modern formulation
      i.e. "Self microemulsifying System". Different doses of SME (Self
      microemulsifying) formulation of L. speciosa leaves extract were evaluated for
      the hepatoprotective activity against carbon tetrachloride induced liver toxicity
      in rats. The parameters evaluated were (a) biochemical parameters like serum
      enzymes: aspartate aminotransferase (AST), serum glutamate pyruvate transaminase
      (ALT), serum alkaline phosphatase (ALP) and total bilirubin (b) liver antioxidant
      parameters as estimation of Lipid peroxidation (LPO), catalase (CAT), Superoxide
      dismutase (SOD) activity and concentration of reduced glutathione (GSH). Oral
      administration of SME formulation provided the significant protection in marker
      enzyme of treated group at 100 mg/kg, p.o. as AST (P < 0.001), ALT (P < 0.001),
      ALP (P < 0.001) and total bilirubin (P < 0.001) comparable to the group treated
      with silymarin. Treatment with SME formulation at the doses of 100 mg/kg, p.o.
      significantly prevented the rise in levels of LPO significantly (P < 0.001). The
      GSH, SOD and CAT contents had significantly (P < 0.001) increased in SME
      formulation treated groups whereas carbon tetrachloride intoxicated group had
      shown significant decrease in these parameters compared to control group.
      Formulation at the dose 100 mg/kg, p.o. has shown maximum protection which was
      almost comparable to those of the normal control and standard. The histological
      observations further uphold the results for hepatoprotective activity.

PMID- 29322006
TI  - Attenuation of quorum-sensing-dependent virulence factors and biofilm formation
      by medicinal plants against antibiotic resistant Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa use small signaling molecules such as acyl homoserine
      lactones (AHLs), which play an important role in release virulence factors and
      toxin for further establishment of host infection. Thus, involving with the QS
      system would provide alternative ways of preventing the pathogenicity. In the
      present study, totally six medicinal plants (Terminalia bellerica, Celastrus
      paniculatus, Kingiodendron pinnatum, Schleichera oleosa, Melastoma malabathricum,
      Garcinia gummi-gutta) were screened for anti-QS activity using biomonitor strain
      of Chromobacterium violaceum CV12472. The primary screening of antimicrobial
      activity of all the plant extracts have inhibited the growth of tested bacterial
      species. Of these at the sub-minimum inhibitory concentration the methanol
      extract of T. bellerica (0.0625-0.5 mg/ml) has significantly inhibited violacein
      production (20.07-66.22%) in C. violaceum (CV12472). Consequently, the extract of
      T. bellerica has reduced the production of pyocyanin, exopolysaccharide and
      biofilm formation in P. aeruginosa strains. Fluorescence and scanning electron
      microscopy analysis confirmed the reduction of biofilm formation in P. aeruginosa
      strains when treated with T. bellerica. GC-MS analysis showed the active
      compounds inhibited the production of virulence factors of P. aeruginosa. The
      results suggest the possible use of this T. bellerica as an anti-QS and anti
      biofilm agent to control Pseudomonas infection. Interference of QS provides an
      important means for the inhibition of bacterial virulence and thus aids in
      treatment strategies.

PMID- 29322007
TI  - Co-administration effects of aqueous extract of turnip leaf and metformin in
      diabetic rats.
AB  - Background: There is a variety of experimentally proven medicinal plants having
      antidiabetic properties but data on herb-drug interaction are very limited.
      Earlier studies indicated that aqueous extract of turnip leaf (AETL) has
      hypoglycemic potential in diabetic animals. The present study was conducted to
      evaluate co-administration effects of AETL and metformin, a commonly used
      antidiabetic drug, in diabetic rats. Methods: Metformin at the two different
      doses (50,100 mg/kg) and AETL at the dose of 400 mg/kg (separately or concurrent
      with metformin) were orally given to streptozotocin-induced diabetic rats for 4
      weeks daily. Fasting blood glucose (FBG) was measured at the times 0, 7, 14, 21
      and 28 days after investigation. At the end of study, liver enzymes activity
      [aspartate aminotransferase (AST) and alanine aminotransferase (ALT)] as well as
      liver histopathology were evaluated. Results: Both treatments could significantly
      decrease FBG levels when they administrated separately. Interestingly, co
      administration of AETL and metformin in a dose dependent manner significantly
      improved hypoglycemic activity of metformin. While neither metformin nor AETL
      could ameliorate liver alterations alone, but in concomitant therapy they
      efficiently attenuated liver enzymes elevation and histological damages.
      Conclusion: The results of the present study demonstrate that combination of
      metformin with AETL enhance the prior effectiveness and reduced the latter
      adverse effects by a synergistic interaction.

PMID- 29322008
TI  - Inhibitory effects of Tabernaemontana divaricata root extract on oxidative stress
      and neuronal loss induced by amyloid beta25-35 peptide in mice.
AB  - In Alzheimer's disease, there are numerous amyloid plaques, neurofibrillary
      tangles, and neuronal loss in several brain areas. Oxidative stress is involved
      in the mechanisms of Abeta-peptide induced neurotoxicity by the generation of
      free radical oxidative stress that may lead to neurodegeneration. Tabernaemontana
      divaricata has various medical properties in Thai folklore medicine including
      prevent forgetfulness or improve memory. The present study aimed to investigate
      the effects of T. divaricata root extract (TDE) on Abeta25-35 peptides induced
      neuronal loss and oxidative stress in mice. Male ICR mice were administered with
      vehicle or TDE (250, 500, and 1000 mg/kg b.w., p.o.) for 28 consecutive days.
      Then, these mice were given a single intracerebroventricular (i.c.v.) injection
      of Abeta25-35 or phosphate buffer saline (PBS) (10 MUg/mouse). The novel object
      recognition (NOR) test was used to determine memory disturbance. In addition, the
      neuronal cells in the cerebral cortex and hippocampus were measured by using
      crystal violet staining and lipid peroxidation was determined by measuring the
      formation of thiobarbituric acid reactive substances. An i.c.v. injection of
      Abeta25-35 peptides could significantly induce memory impairment, increase level
      of lipid peroxidation including the neuronal loss in CA3 of hippocampus. However,
      the mice pretreated with TDE could prevent the memory loss, neuronal loss and
      decrease lipid peroxidation. These results suggest the potential therapeutic
      value in dementia of TDE through its antioxidant property.

PMID- 29322009
TI  - Improvement of spatial learning and memory, cortical gyrification patterns and
      brain oxidative stress markers in diabetic rats treated with Ficus deltoidea leaf
      extract and vitexin.
AB  - Despite the fact that Ficus deltoidea and vitexin played important roles in
      controlling hyperglycemia, an effective mitigation strategy dealing with
      cognitive deficit observed in diabetes, little is known about its neuroprotective
      effects. The study is aimed to determine changes in behavioral, gyrification
      patterns and brain oxidative stress markers in streptozotocin (STZ)-induced
      diabetic rats following F. deltoidea and vitexin treatments. Diabetic rats were
      treated orally with metformin, methanolic extract of F. deltoidea leaves and
      vitexin for eight weeks. Morris water maze (MWM) test was performed to evaluate
      learning and memory functions. The patterns of cortical gyrification were
      subsequently visualized using micro-computed tomography (micro-CT).
      Quantification of brain oxidative stress biomarkers, insulin, amylin as well as
      serum testosterone were measured using a spectrophotometer. The brain fatty acid
      composition was determined using gas chromatography (GC). Biochemical variation
      in brain was estimated using Fourier transform infrared (FT-IR) spectroscopy.
      Results showed that oral administration of F. deltoidea extract and vitexin to
      diabetic rats attenuated learning and memory impairment, along with several
      clusters of improved gyrification. Both treatments also caused a significant
      increase in the superoxide dismutase (SOD) and glutathione peroxidase (GPx)
      values, as well as a significant reduction of TBARS. Strikingly, improvement of
      cortical gyrification, spatial learning and memory are supported by serum
      testosterone levels, fatty acid composition of brain and FT-IR spectra.

PMID- 29322010
TI  - Beneficiary effect of Commiphora mukul ethanolic extract against high fructose
      diet induced abnormalities in carbohydrate and lipid metabolism in wistar rats.
AB  - The present study was proposed to elucidate the effect of Commiphora mukul gum
      resin elthanolic extract treatment on alterations in carbohydrate and lipid
      metabolisms in rats fed with high-fructose diet. Male Wistar rats were divided
      into four groups: two of these groups (group C and C+CM) were fed with standard
      pellet diet and the other two groups (group F and F+CM) were fed with high
      fructose (66 %) diet. C. mukul suspension in 5% Tween-80 in distilled water (200
      mg/kg body weight/day) was administered orally to group C+CM and group F+CM. At
      the end of 60-day experimental period, biochemical parameters related to
      carbohydrate and lipid metabolisms were assayed. C. mukul treatment completely
      prevented the fructose-induced increased body weight, hyperglycemia, and
      hypertriglyceridemia. Hyperinsulinemia and insulin resistance observed in group F
      decreased significantly with C. mukul treatment in group F+CM. The alterations
      observed in the activities of enzymes of carbohydrate and lipid metabolisms and
      contents of hepatic tissue lipids in group F rats were significantly restored to
      near normal values by C. mukul treatment in group F+CM. In conclusion, our study
      demonstrated that C. mukul treatment is effective in preventing fructose-induced
      insulin resistance and hypertriglyceridemia while attenuating the fructose
      induced alterations in carbohydrate and lipid metabolisms by the extract which
      was further supported by histopathological results from liver samples which
      showed regeneration of the hepatocytes. This study suggests that the plant can be
      used as an adjuvant for the prevention and/or management of insulin resistance
      and disorders related to it.

PMID- 29322011
TI  - Safety evaluation of Bon-sante cleanser(r) polyherbal in male Wistar rats:
      Further investigations on androgenic and toxicological profile.
AB  - Background: The global increase in acceptance and use of herbal remedies in
      recent times is still accompanied with poor knowledge of their potential adverse
      effects and the toxicological implications of their use are underestimated.
      Methods: Bon-sante Cleanser(r) (BSC), a polyherbal containing Anogeissus
      leiocarpus, Terminalia ivorensis, Massularia acuminate and Macuna pruriens, is an
      "energizer and hormone booster". We assessed the effect of BSC on reproductive
      function after administration for 60 days in male Wistar rats. Rats (150-300 g)
      were assigned into four groups of 8/group. Control received distilled water (10
      ml/kg) while other groups received BSC 250, 500 and 1000 mg/kg/day p.o.
      respectively. Animals were euthanized by cervical dislocation and samples
      collected for analysis. Results: BSC (250 mg/kg) elevated (p < 0.05) follicle
      stimulating hormone and luteinizing hormone levels respectively. BSC decreased
      sperm motility and the live-dead ratio at 1000 mg/kg and reduced reproductive
      hormone at 500 mg/kg and 1000 mg/kg respectively. BSC at 500 mg/kg increased (p <
      0.05, F = 3.18-13.21) testicular reduced glutathione level (50.3%) and catalase
      (43.7%) but not activities of superoxide dismutase, glutathione S-transferase,
      and malondialdehyde level. Further, BSC influenced Mg, Zn, Cu, P, Mn, Ni and Fe
      levels (p < 0.05). BSC (1000 mg/kg) decreased testis weight (p < 0.05) and
      induced mild inflammation characterized by atrophic tubules. Conclusion: Overall,
      our data suggest BSC at low doses may increase reproductive hormones regulated by
      FSH and LH as observed in this study. However, BSC administration should be done
      with caution as it may induce reproductive toxicity in large doses.

PMID- 29322012
TI  - Inhibition of aqueous extracts of Solanum nigrum (AESN) on oral cancer through
      regulation of mitochondrial fission.
AB  - The present study is designed to investigate the anti-oral cancer properties of
      Solanum nigrum on oral squamous cell carcinoma. S. nigrum is a Chinese herb used
      for suppression of various cancers. However, the inhibition of S. nigrum on oral
      cancer is unclear. Therefore, human oral squamous cancer cells (SCC)-4 were used
      to evaluate the effect of aqueous extracts of S. nigrum (AESN) on cancer cell
      proliferation, cell cycle, mitochondrial function and apoptosis. The SCC-4 cells
      were treated by AESN to evaluate the inhibition of cell proliferation and
      mitochondrial function in vitro. Our results suggested that AESN markedly
      increased reactive oxygen species production. AESN also promoted caspase-9 and
      caspase-3 activation and subsequent triggering of the mitochondrial apoptotic
      pathway. The inhibition of glucose uptake was alleviated mediated by a dose
      dependent manner in SCC-4 cells with AESN treatment for 24 h, resulting in
      mitochondrial fission. These results suggested that AESN has potential to be used
      as a functional food in adjuvant chemotherapy for treating human oral cancer by
      suppression of mitochondrial function.

PMID- 29322013
TI  - Dillenia indica L. attenuates diabetic nephropathy via inhibition of advanced
      glycation end products accumulation in STZ-nicotinamide induced diabetic rats.
AB  - The present study was aimed to evaluate advanced glycation end products (AGEs)
      inhibitory activity of alcohol and hydro-alcohol extract (DAE and DHE) of
      Dillenia indica L. (Family: Dilleniaceae) and its potential in treatment of
      diabetic nephropathy by targeting markers of oxidative stress. D. indica was
      evaluated for its in vitro inhibitory activity against formation of AGEs by using
      bovine serum albumin. Diabetes was induced in male Wistar rats by streptozotocin
      (65 mg/kg i.p.) 15 min after nicotinamide (230 mg/kg, i.p.) administration.
      Diabetic rats were treated with different doses of extracts (100, 200 and 400
      mg/kg) to analyze their nephroprotective effect. Tissue antioxidant enzymes level
      was measured along with the formation of AGEs in kidney to assess the effect of
      D. indica in ameliorating oxidative stress. D. indica showed significant
      inhibition of AGEs formation in vitro. D. indica produced significant attenuation
      in the glycemic status, renal parameter, lipid profile and level of antioxidant
      enzymes proving efficacy in diabetic nephropathy. Moreover, D. indica produced
      significant reduction in the formation of AGEs in kidneys. The present study
      concludes that D. indica as a possible therapeutic agent against diabetic
      nephropathy.

PMID- 29322014
TI  - Protective effects of salep against isoniazid liver toxicity in wistar rats.
AB  - Introduction: Isoniazid is a drug for treatment of tuberculosis. One of the main
      side effects of this drug is hepatotoxicity, which is a major cause of treatment
      interruption in tuberculosis. This study is about the preventive effect of Salep
      on this side effect of isoniazid. Materials and methods: This study is an
      experimental study in which the preventive effect of salep on isoniazid
      hepatotoxicity is evaluated. In this study 56 rats were randomly placed in 7
      eight members groups including: control group, sham, isoniazid and four
      isoniazid/salep groups. At the end of the study the laboratory criteria and
      histological features of liver toxicity were compared in different mentioned
      groups. Results: Significant lower serum levels of liver enzymes, billirubin, MDA
      and TOC; and significant higher levels of TAC and total proteins, were revealed
      in isoniazid/salep group in compare to isoniazid alone group.In addition,
      histological studies had not showed liver injury in isoniazid/salep group, while
      there was significant liver injury in isoniazid alone group. Conclusions: Orchid
      extract (salep), probably because of its antioxidant properties, prevent the
      destructive effects of isoniazid on the liver.

PMID- 29322015
TI  - Kingiodendron pinnatum, a pharmacologically effective alternative for Saraca
      asoca in an Ayurvedic preparation, Asokarishta.
AB  - Saraca asoca (Fabaceae) is a prime ingredient in Asokarishta, a well-known
      Ayurvedic preparation for gynecological ailments. Due to scarcity, adulteration
      or substitution of related raw drugs is a common practice in its preparation. The
      bark of Kingiodendron pinnatum (Roxb. ex DC.) Harms, morphologically similar to
      S. asoca (Asoka) is a widely used substitute. The present study aimed to evaluate
      the pharmacological effectiveness of K. pinnatum as an alternative for S. asoca
      in Asokarishta by determining the inhibitory effect of estrogen induced uterus
      endometrial thickening in immature female rats. Arishta was prepared using S.
      asoca and with the substitute, K. pinnatum as per Ayurvedic Pharmacopeia. Uterus
      endometrial thickening was induced by the administration of estradiol (20 MUg/kg
      b. wt, i.p) to 8-day-old rats for 5 alternate days. On day 16, following
      estradiol administration, the serum estrogen level was found elevated to 156.5 +/
      8 pg/ml from the normal value 32.4 +/- 5 pg/ml and consequently increased the
      thickness of uterus endometrium from 16.7 +/- 1.4 to 75.2 +/- 15.3 MUm. Upon oral
      administration of 400 MUl/kg b. wt Asokarishta (ASA) and Arishta made with K.
      pinnatum (AKP), the thickening was reduced to 42.5 +/- 12.7 and 47.1 +/- 10.5 MUm
      and the estrogen level diminished to 102.6 +/- 10 and 97.3 +/- 8 pg/ml,
      respectively. Arishta also reduced the chronic/acute inflammations in mice and
      improved the antioxidant status of rats. No toxic symptom was observed in the
      animals by the treatment of Arishta. The study supports the use of K. pinnatum as
      an alternative to S. asoca in Asokarishta and gives a scientific validation for
      Asokarishta in gynecological ailments.

PMID- 29322016
TI  - Evaluation of in vitro and in vivo antileishmanial potential of bergenin rich
      Bergenia ligulata (Wall.) Engl. root extract against visceral leishmaniasis in
      inbred BALB/c mice through immunomodulation.
AB  - Background: Medicinal plants with immunomodulatory properties can provide good
      alternative therapeutics for curing visceral leishmaniasis. Bergenia ligulata
      (Wall.) Engl. is an interesting plant with strong antioxidant, antimicrobial,
      immunomodulatory and hepatoprotective properties. Aim: The present study was
      planned to determine the antileishmanial activity of plant extract by modulating
      the immune responses of inbred BALB/c mice. Methodology: Bergenin, the principle
      active component of B. ligulata, was quantitated in crude extract by performing
      RP-HPLC. The therapeutic potential was assessed through in vitro antileishmanial
      activity and in mice model through parasite load, cytokine assays, IgG antibody
      levels, DTH responses, histopathology and biochemical enzyme assays. Results: B.
      ligulata showed the presence of glycosides, saponins, carbohydrates, tannins,
      flavonoids and bergenin which contributed to the antileishmanial activity of
      extract with IC50 of 22.70 MUg/mL. Furthermore, the higher dose significantly
      reduced the parasite load by 95.56 %. The reduction was further associated with
      significant enhancement of IL-12 and IFN-gamma levels in comparison to IL-10 and
      IL-4 cytokines. The switching towards Th1 type of immune response was also
      confirmed by elevated antibody levels of IgG2a isotype as compared to IgG1 as
      well as increased DTH responses. The histology of liver and kidney further
      complimented the non toxic nature of plant extract in addition to its negligible
      toxicity on HeLa cells. Conclusions: The current study revealed the significant
      antileishmanial and immunomodulatory properties of this plant extract against
      murine visceral leishmaniasis. Further, the bioactive components will be explored
      to assess their efficacy for the development of safe and cost effective drug.

PMID- 29322017
TI  - Clinical profile and long-term follow-up of 32 patients with postoperative
      permanent hypoparathyroidism.
AB  - Background: Parathyroid failure is the most common complication after total
      thyroidectomy but permanent impairment of the parathyroid function is unusual.
      Limited data is available assessing long-term follow-up, quality of life and
      complications occurring in patients with permanent hypoparathyroidism (PH). We
      aimed to assess the incidence of complications derived from PH status, their
      influence on the quality of life perceived by PH patients and its relation to
      standard medical treatment with calcium salts and active vitamin D analogues.
      Methods: Cross-sectional observational study of consecutive patients undergoing
      total thyroidectomy who developed PH and were followed at least twice a year at a
      referral endocrine surgery unit. PH was defined as intact parathyroid hormone
      (iPTH) levels <13 pg/mL and the need for replacement therapy with calcium and/or
      vitamin D for at least 1 year after surgery. Quality of life was assessed using
      the SF-36 questionnaire. Data regarding doses and type of vitamin D analogues and
      calcium supplementation, serum calcium fluctuations, bone densitometry and renal
      ultrasound were recorded. Results: The cohort included 32 patients (3 male/29
      female) with a mean age of 51.2+/-15.2 years. The mean follow-up was 78+/-68
      months and the total follow-up length was 70,080 PH patient/days. Five (15.6%)
      patients showed a decreased renal function. At least one clinical adverse event
      was observed in 18 (56.3%) patients. There was a slight decrease of the
      punctuation in the SF-36 questionnaire for the perceived quality of life that was
      only significant for the emotional role. Conclusions: PH and its treatment carry
      a mild to moderate burden of illness if followed closely. During a mean follow-up
      of nearly 6 years, only half of the patients suffered a relevant clinical event
      with little impact on their quality of life.

PMID- 29322018
TI  - A nomogram to predict the likelihood of permanent hypoparathyroidism after total
      thyroidectomy based on delayed serum calcium and iPTH measurements.
AB  - Background: Retrospective studies have shown that delayed high-normal serum
      calcium and detectable iPTH are independent variables positively influencing
      outcome of prolonged parathyroid failure after total thyroidectomy (TT). The aim
      of the present study was to examine prospectively the ability of these two
      variables to predict permanent hypoparathyroidism in patients under replacement
      therapy for postoperative hypocalcemia. Methods: Prospective observational
      multicenter study of patients undergoing TT followed by postoperative parathyroid
      failure (serum calcium <8 mg/dL within 24 h and PTH <15 pg/mL 4 h after surgery).
      Serum calcium, vitamin D and iPTH were determined before thyroidectomy, 24 h
      after surgery, at 1 month and then periodically until recovery of the parathyroid
      function or permanent hypoparathyroidism was diagnosed after at least 1 year
      follow-up. Results: Some 145 patients with postoperative hypocalcemia were
      investigated [s-Ca24h 7.5 (0.5) mg/dL]. Hypocalcemia recovered within 30 days in
      91 (63%) patients and 54 (37%) developed protracted hypoparathyroidism {iPTH 5.8
      [4] pg/mL at 1 month}, of whom 32 recovered within 1 year and 22 developed
      permanent hypoparathyroidism. Protracted hypoparathyroidism was related to few
      parathyroid glands remaining in situ (PGRIS). Serum calcium concentration (mg/dL)
      at 1 postoperative month correlated positively with the rate of recovery
      (percent) from protracted hypoparathyroidism: <8.5 (20%); 8.5-9 (29%); 9.1-9.5
      (70%); 9.6-10 (89%); >10 (83%) (P=0.013). Serum iPTH at 1 month was also higher
      (7.3 vs. 3.7 pg/mL; P=0.002) in recovered protracted hypoparathyroidism. The
      combination of both variables predicts the likelihood of recovery of the
      parathyroid function with >90% accuracy. Conclusions: High-normal serum calcium
      and low but detectable iPTH concentrations at 1 month after TT were associated
      with better outcome of protracted hypoparathyroidism. A nomogram combining both
      variables may guide medical treatment and monitoring of post-thyroidectomy
      prolonged hypoparathyroidism.

PMID- 29322019
TI  - To identify or not to identify parathyroid glands during total thyroidectomy.
AB  - Hypoparathyroidism is one of the most common complications after total
      thyroidectomy and may impose a significant burden to both the patient and
      clinician. The extent of thyroid resection, surgical techniques, concomitant
      central neck dissection, parathyroid gland (PG) autotransplantation and
      inadvertent parathyroidectomy have long been some of the risk factors for
      postoperative hypoparathyroidism. Although routine identification of PGs has
      traditionally been advocated by surgeons, recent evidence has suggested that
      perhaps identifying fewer number of in situ PGs during surgery (i.e., selective
      identification) may further lower the risk of hypoparathyroidism. One explanation
      is that visual identification may often lead to subtle damages to the nearby
      blood supply of the in situ PGs and that may increase the risk of
      hypoparathyroidism. However, it is worth highlighting the current literature
      supporting either approach (i.e., routine vs. selective) remains scarce and
      because of the significant differences in study design, inclusions, definitions
      and management protocol between studies, a pooled analysis on this important but
      controversial topic remains an impossible task. Furthermore, it is worth nothing
      that identification of PGs does not equal safe preservation, as some studies
      demonstrated that it is not the number of PGs identified, but the number of PG
      preserved in situ that matters. Therefore a non-invasive, objective and reliable
      way to localize PGs and assess their viability intra-operatively is warranted. In
      this aspect, modern technology such as the indocyanine green (ICG) as near
      infrared fluorescent dye for real-time in situ PG perfusion monitoring may have a
      potential role in the future.

PMID- 29322020
TI  - A reappraisal of vascular anatomy of the parathyroid gland based on fluorescence
      techniques.
AB  - Identification of the parathyroid glands (PGs) during thyroid surgery may prevent
      their inadvertent surgical removal and prevent postoperative hypoparathyroidism.
      However, identification of the PGs does not guarantee their function, and their
      vascular supply needs to be preserved as well. The recent introduction of
      intraoperative indocyanine green (ICG) fluorescent angiography of the PGs during
      thyroid surgery allows for the appraisal of the vascular anatomy and evaluation
      of PG function. The use of this tool could lead to a significant reduction in the
      rate of postoperative hypoparathyroidism, as it allows surgeons to adapt their
      surgical technique for the preservation of the PGs. ICG fluorescent angiography
      is currently the only available real-time tool to assess the vascular blood
      supply of each individual PG intraoperatively and can thus assist surgeons in
      their decision-making. Herein, we review the relevant literature.

PMID- 29322021
TI  - The role and timing of parathyroid hormone determination after total
      thyroidectomy.
AB  - Postoperative hypocalcemia is a common complication of total thyroidectomy
      resulting from manipulation, resection, or devascularization of the parathyroid
      glands. Parathyroid hormone (PTH) levels assessed in the perioperative period
      have been used to predict development of hypocalcemia. Articles examining the
      role of PTH measurement in the perioperative period following total or completion
      thyroidectomy are reviewed. Focus is placed on the timing of PTH measurement and
      the ability to predict which patients will develop hypocalcemia requiring
      supplementation. Postoperative PTH determination is highly accurate in predicting
      the development of hypocalcemia. Studies have examined PTH levels drawn at
      differing time points, ranging from intraoperatively until postoperative day 1
      (POD1) with similar accuracy. This data is used to guide postoperative selective
      calcium and calcitriol supplementation in patients at highest risk for
      hypocalcemia. When evaluated within the first 4 hours postoperatively, predictive
      accuracy is maintained but can allow for earlier discharge for those patients at
      lower risk. Alternatively, some authors argue for routine supplementation, which
      can reduce the rate of postoperative hypocalcemia but increases the rate of
      unnecessary supplementation and potential risks associated with hypercalcemia.
      PTH determination at four hours after total thyroidectomy is an accurate
      predictor of hypocalcemia and can guide selective calcium supplementation for
      those at high risk, as well as facilitate a safe earlier hospital discharge for
      those at low risk of developing postoperative hypocalcemia.

PMID- 29322022
TI  - Less than total thyroidectomy for goiter: when and how?
AB  - Benign goiter is the most common endocrine disease that requires surgery,
      especially in endemic areas suffering from iodine-deficiency. Recent European and
      American guidelines recommended total thyroidectomy for the surgical treatment of
      multinodular goiter. Total thyroidectomy has now become the technique of choice
      and is widely considered the most reliable approach in preventing recurrence.
      Nevertheless, total thyroidectomy carries a substantial risk in terms of
      hypoparathyroidism and the morbidity associated with injury to the inferior
      laryngeal nerve. In this context, partial/less-than-total thyroidectomy is being
      considered once again as a viable alternative. This review will discuss the
      extent of thyroid surgery for benign disease and the impact of the surgical
      protocol on the patient- and surgeon-specific risk factors for specific
      complication rates.

PMID- 29322023
TI  - Incidence, prevalence and risk factors for post-surgical hypocalcaemia and
      hypoparathyroidism.
AB  - Hypocalcaemia following thyroid surgery is common and is associated with
      significant short and long term morbidity. Damage to or devascularisation of
      parathyroid glands is the predominant underlying mechanism; although other
      factors such as hungry bone syndrome may occasionally contribute to it in the
      immediate post-operative period. The reported incidence of post-surgical
      hypocalcaemia and/or hypoparathyroidism (PoSH) varies significantly in the
      literature; the variation thought to be at least partly due to differences in the
      definitions used. Figures on the prevalence of chronic or long term post-surgical
      hypocalcaemia in the population are unclear. Risk factors for PoSH have been
      extensively studied in recent years and may be classified into patient, disease
      and surgery related factors. Some risk factors are modifiable; but both
      modifiable and non-modifiable factors help in generating a risk profile that may
      be used to select patients for preventative measures and/or changes in surgical
      strategy. This narrative review discusses recent literature on the incidence,
      prevalence and risk factors for PoSH.

PMID- 29322024
TI  - Hypocalcaemia and permanent hypoparathyroidism after total/bilateral
      thyroidectomy in the BAETS Registry.
AB  - The UK Registry of Endocrine and Thyroid Surgeons (UKRETS) has been operated by
      the British Association of Endocrine and Thyroid Surgeons (BAETS) and Dendrite
      Clinical Systems Ltd. in a web-based electronic format since 2004. Data on over
      90,000 endocrine procedures have been collected to date. Analysis of those cases
      undergoing bilateral thyroid resections in the interval July 2010 to June 2015
      demonstrates that hypocalcaemia remains the commonest complication of thyroid
      surgery. After first-time total thyroidectomy, 23.6% of patients develop
      hypocalcaemia, defined as a serum calcium <2.10 mmol/L (or <1.20 mmol/L ionized
      calcium) on the first post-operative day. Most require treatment with calcium +/-
      vitamin D supplements, with around 38% of all patients being treated by the time
      of discharge from the index admission. By 6 months post-operative, 7.3% of
      patients remain on calcium/vitamin D supplements, reflecting persistent (though
      not necessarily permanent) hypoparathyroidism. Risk factors for persistent
      hypocalcaemia are principally concomitant level VI lymph node dissection [odds
      ratio (OR) =2.73]; re-operative surgery (OR =1.44); and inter-surgeon variation.

PMID- 29322026
TI  - The PGRIS and parathyroid splinting concepts for the analysis and prognosis of
      protracted hypoparathyroidism.
AB  - Most patients with hypocalcemia after total thyroidectomy will recover the
      parathyroid function in a few weeks, but some 20-30% of them will still be in the
      need for replacement therapy one month after surgery and about 5-10% of those
      will develop permanent hypoparathyroidism. Although postoperative hypocalcemia
      has been related to several demographic and metabolic causes, parathyroid hormone
      (PTH) decline, resulting from autotransplantation, inadvertent excision or
      devascularization of the parathyroid glands, is the common final pathway. The
      number of parathyroid glands remaining in situ (PGRIS) is a key variable to
      understand the pathogenesis of protracted hypoparathyroidism and the chances for
      restoration of the parathyroid function. Normal-high serum calcium concentration,
      probably achieved by a more intensive medical treatment at the time of hospital
      discharge, has been identified as an independent variable favoring recovery of
      the parathyroid function. This we refer to as parathyroid splinting, a hypothesis
      holding that putting the injured parathyroid parenchyma at rest after
      thyroidectomy may improve long-term outcome of protracted hypoparathyroidism.

PMID- 29322025
TI  - Short and long-term impact of parathyroid autotransplantation on parathyroid
      function after total thyroidectomy.
AB  - The most common complication of total thyroidectomy is parathyroid insufficiency.
      Acute, transient, post-operative hypoparathyroidism increases length of
      hospitalization, morbidity and cost associated with total thyroidectomy. While
      permanent hypoparathyroidism poses a significant medical burden with lifetime
      medication, regular follow up and considerable disease burden related to chronic
      renal failure and other sequelae. Parathyroid autotransplantation has been
      demonstrated to result in biochemically functional grafts, leading to the
      procedures' common use during total thyroidectomy. The clearest indications for
      parathyroid auto transplantation are inadvertently removed or devascularized
      parathyroid glands. Some centers utilize routine autotransplantation to reduce
      the risk of permanent hypoparathyroidism. Novel fluorescence techniques to aid in
      parathyroid detection during thyroid surgery are under evaluation. This review
      aims to define the role and impact of parathyroid autotransplantation undertaken
      during total thyroidectomy.

PMID- 29322027
TI  - Allograft for Myeloma: Examining Pieces of the Jigsaw Puzzle.
AB  - Multiple myeloma (MM) cure remains elusive despite the availability of newer anti
      myeloma agents. Patients with high-risk disease often suffer from early relapse
      and short survival. Allogeneic hematopoietic cell transplantation (allo-HCT) is
      an "immune-based" therapy that has the potential to offer long-term remission in
      a subgroup of patients, at the expense of high rates of transplant-related
      morbidity and mortality. Donor lymphocyte infusion (DLI) upon disease relapse
      after allo-HCT is able to generate an anti-myeloma response suggestive of a graft
      versus-myeloma effect. Allo-HCT provides a robust platform for additional immune
      based therapy upon relapse including DLI and, maintenance with immunomodulatory
      drugs and immunosuppressive therapy. There have been conflicting findings from
      randomized prospective trials questioning the role of allo-HCT. However, to this
      date, allo-HCT remains the only potential curable treatment for MM and its
      therapeutic role needs to be better defined especially for patients with high
      risk disease. This review examines different aspects of this treatment and
      summarizes ongoing attempts at improving its therapeutic index.

PMID- 29322030
TI  - Editorial: Update on the Treatment of Metastatic Non-small Cell Lung Cancer
      (NSCLC) in New Era of Personalised Medicine.

PMID- 29322029
TI  - Influencing Cancer Screening Participation Rates-Providing a Combined Cancer
      Screening Program (a 'One Stop' Shop) Could Be a Potential Answer.
AB  - Introduction: Participation in established cancer screening programs remains
      variable. Therefore, a renewed focus on how to increase screening uptake,
      including addressing structural barriers such as time, travel, and cost is
      needed. One approach could be the provision of combined cancer screening, where
      multiple screening tests are provided at the same time and location (essentially
      a 'One Stop' screening shop). This cohort study explored both cancer screening
      behavior and the acceptability of a combined screening approach. Methods:
      Participants of the North Western Adelaide Health Study (NWAHS), South Australia
      were invited to participate in a questionnaire about cancer screening behaviors
      and the acceptability of a proposed 'One Stop' cancer screening shop. Data were
      collected from 10th August 2015 to 18th January 2016, weighted for selection
      probability, age, and sex and analyzed using descriptive and multivariable
      logistic regression analysis. Results: 1,562 people, 52% female (mean age 54.1
      years +/- 15.2) participated. Reported screening participation was low, the
      highest being for Pap Smear (34.4%). Common reasons for screening participation
      were preventing sickness (56.1%, CI 53.2-59.0%), maintaining health (51%, CI 48
      53.9%), and free program provision (30.9%, CI 28.2-33.6%). Females were less
      likely to state that screening is not beneficial [OR 0.37 (CI 0.21-0.66), p <
      0.001] and to cite sickness prevention [OR 2.10 (CI 1.46-3.00), p < 0.001] and
      free program [OR 1.75 (CI 1.22-2.51), p < 0.003] as reasons for screening
      participation. Of those who did not participate, 34.6% (CI 30.3-39.1%) stated
      that there was nothing that discouraged them from participation, with 55- to 64
      year olds [OR 0.24 (CI 0.07-0.74), p < 0.04] being less likely to cite this
      reason. 21% (CI 17.2-24.8%) thought they did not need screening, while a smaller
      proportion stated not having time (6.9%, CI 4.9-9.7%) and the costs associated
      with screening (5.2%, CI 3.5-7.7%). The majority of participants (85.3%, CI 81.9
      88.2%) supported multiple screening being offered at the same time and location.
      Conclusion: Identified screening behaviors in this study are similar to those
      reported in the literature. The high support for the concept of combined cancer
      screening demonstrates that this type of approach is acceptable to potential end
      users and warrants further investigation.

PMID- 29322028
TI  - High-Content Monitoring of Drug Effects in a 3D Spheroid Model.
AB  - A recent decline in the discovery of novel medications challenges the widespread
      use of 2D monolayer cell assays in the drug discovery process. As a result, the
      need for more appropriate cellular models of human physiology and disease has
      renewed the interest in spheroid 3D culture as a pertinent model for drug
      screening. However, despite technological progress that has significantly
      simplified spheroid production and analysis, the seeming complexity of the 3D
      approach has delayed its adoption in many laboratories. The present report
      demonstrates that the use of a spheroid model may be straightforward and can
      provide information that is not directly available with a standard 2D approach.
      We describe a cost-efficient method that allows for the production of an array of
      uniform spheroids, their staining with vital dyes, real-time monitoring of drug
      effects, and an ATP-endpoint assay, all in the same 96-well U-bottom plate. To
      demonstrate the method performance, we analyzed the effect of the preclinical
      anticancer drug MLN4924 on spheroids formed by VCaP and LNCaP prostate cancer
      cells. The drug has different outcomes in these cell lines, varying from cell
      cycle arrest and protective dormancy to senescence and apoptosis. We demonstrate
      that by using high-content analysis of spheroid arrays, the effect of the drug
      can be described as a series of EC50 values that clearly dissect the cytostatic
      and cytotoxic drug actions. The method was further evaluated using four standard
      cancer chemotherapeutics with different mechanisms of action, and the effect of
      each drug is described as a unique multi-EC50 diagram. Once fully validated in a
      wider range of conditions, this method could be particularly valuable for
      phenotype-based drug discovery.

PMID- 29322031
TI  - Inhibition of Wnt Signaling Pathways Impairs Chlamydia trachomatis Infection in
      Endometrial Epithelial Cells.
AB  - Chlamydia trachomatis infections represent the predominant cause of bacterial
      sexually transmitted infections. As an obligate intracellular bacterium, C.
      trachomatis is dependent on the host cell for survival, propagation, and
      transmission. Thus, factors that affect the host cell, including nutrition, cell
      cycle, and environmental signals, have the potential to impact chlamydial
      development. Previous studies have demonstrated that activation of Wnt/beta
      catenin signaling benefits C. trachomatis infections in fallopian tube epithelia.
      In cervical epithelial cells chlamydiae sequester beta-catenin within the
      inclusion. These data indicate that chlamydiae interact with the Wnt signaling
      pathway in both the upper and lower female genital tract (FGT). However, hormonal
      activation of canonical and non-canonical Wnt signaling pathways is an essential
      component of cyclic remodeling in another prominent area of the FGT, the
      endometrium. Given this information, we hypothesized that Wnt signaling would
      impact chlamydial infection in endometrial epithelial cells. To investigate this
      hypothesis, we analyzed the effect of Wnt inhibition on chlamydial inclusion
      development and elementary body (EB) production in two endometrial cell lines,
      Ishikawa (IK) and Hec-1B, in nonpolarized cell culture and in a polarized
      endometrial epithelial (IK)/stromal (SHT-290) cell co-culture model. Inhibition
      of Wnt by the small molecule inhibitor (IWP2) significantly decreased inclusion
      size in IK and IK/SHT-290 cultures (p < 0.005) and chlamydial infectivity (p <=
      0.01) in both IK and Hec-1B cells. Confocal and electron microscopy analysis of
      chlamydial inclusions revealed that Wnt inhibition caused chlamydiae to become
      aberrant in morphology. EB formation was also impaired in IK, Hec-1B and IK/SHT
      290 cultures regardless of whether Wnt inhibition occurred throughout, in the
      middle (24 hpi) or late (36 hpi) during the development cycle. Overall, these
      data lead us to conclude that Wnt signaling in the endometrium is a key host
      pathway for the proper development of C. trachomatis.

PMID- 29322032
TI  - The Multiple Localized Glyceraldehyde-3-Phosphate Dehydrogenase Contributes to
      the Attenuation of the Francisella tularensis dsbA Deletion Mutant.
AB  - The DsbA homolog of Francisella tularensis was previously demonstrated to be
      required for intracellular replication and animal death. Disruption of the dsbA
      gene leads to a pleiotropic phenotype that could indirectly affect a number of
      different cellular pathways. To reveal the broad effects of DsbA, we compared
      fractions enriched in membrane proteins of the wild-type FSC200 strain with the
      dsbA deletion strain using a SILAC-based quantitative proteomic analysis. This
      analysis enabled identification of 63 proteins with significantly altered amounts
      in the dsbA mutant strain compared to the wild-type strain. These proteins
      comprise a quite heterogeneous group including hypothetical proteins, proteins
      associated with membrane structures, and potential secreted proteins. Many of
      them are known to be associated with F. tularensis virulence. Several proteins
      were selected for further studies focused on their potential role in tularemia's
      pathogenesis. Of them, only the gene encoding glyceraldehyde-3-phosphate
      dehydrogenase, an enzyme of glycolytic pathway, was found to be important for
      full virulence manifestations both in vivo and in vitro. We next created a viable
      mutant strain with deleted gapA gene and analyzed its phenotype. The gapA mutant
      is characterized by reduced virulence in mice, defective replication inside
      macrophages, and its ability to induce a protective immune response against
      systemic challenge with parental wild-type strain. We also demonstrate the
      multiple localization sites of this protein: In addition to within the cytosol,
      it was found on the cell surface, outside the cells, and in the culture medium.
      Recombinant GapA was successfully obtained, and it was shown that it binds host
      extracellular serum proteins like plasminogen, fibrinogen, and fibronectin.

PMID- 29322034
TI  - Increased Neutrophil Secretion Induced by NLRP3 Mutation Links the Inflammasome
      to Azurophilic Granule Exocytosis.
AB  - Heterozygous mutations in the NLRP3 gene in patients with cryopyrin associated
      periodic syndrome (CAPS) lead to hyper-responsive inflammasome function. CAPS is
      a systemic auto-inflammatory syndrome characterized by the activation of the
      innate immune system induced by elevated pro-inflammatory cytokines, but the
      involvement of selective innate immune cells in this process is not fully
      understood. Neutrophil secretion and the toxic components of their granules are
      mediators of inflammation associated with several human diseases and inflammatory
      conditions. Here, using the Nlrp3A350V inducible mouse model (MWS CreT) that
      recapitulates human patients with the A352V mutation in NLRP3 observed in the
      Muckle-Wells sub-phenotype of CAPS, we studied the relationship between hyper
      activation of the inflammasome and neutrophil exocytosis. Using a flow cytometry
      approach, we show that Nlrp3A350V (MWS) neutrophils express normal basal levels
      of CD11b at the plasma membrane and that the upregulation of CD11b from secretory
      vesicles in response to several plasma membrane or endocytic agonist including
      the bacterial-derived mimetic peptide formyl-Leu-Met-Phe (fMLF) and the
      unmethylated oligonucleotide CpG is normal in MWS neutrophils. Significant but
      modest CD11b upregulation in MWS neutrophils compared to wild type was only
      observed in response to GM-CSF and CpG. The same pattern was observed for the
      secretion of matrix metalloproteinase-9 (MMP-9) from gelatinase granules in that
      MMP-9 secretion in MWS neutrophils was not different from that observed in wild
      type neutrophils except when stimulated with GM-CSF and CpG. In contrast,
      azurophilic granule secretion, whose cargoes constitute the most toxic secretory
      and pro-inflammatory factors of the neutrophil, was markedly dysregulated in MWS
      neutrophils under both basal and stimulated conditions. This could not be
      attributed to paracrine effects of secretory cytokines because IL-1beta secretion
      by neutrophils was undetectable under these experimental conditions. The
      increased azurophilic granule exocytosis in MWS neutrophils was attenuated by
      treatment with the neutrophil exocytosis inhibitor Nexinhib20. In agreement with
      a possible neutrophil contribution to systemic inflammation in CAPS, the levels
      of neutrophil secretory proteins were significantly elevated in the plasma from
      Nlrp3A350V mice. Altogether, our data indicates an azurophilic granule-selective
      dysregulation of neutrophil exocytosis in CAPS.

PMID- 29322033
TI  - Cattle Tick Rhipicephalus microplus-Host Interface: A Review of Resistant and
      Susceptible Host Responses.
AB  - Ticks are able to transmit tick-borne infectious agents to vertebrate hosts which
      cause major constraints to public and livestock health. The costs associated with
      mortality, relapse, treatments, and decreased production yields are economically
      significant. Ticks adapted to a hematophagous existence after the vertebrate
      hemostatic system evolved into a multi-layered defense system against foreign
      invasion (pathogens and ectoparasites), blood loss, and immune responses.
      Subsequently, ticks evolved by developing an ability to suppress the vertebrate
      host immune system with a devastating impact particularly for exotic and
      crossbred cattle. Host genetics defines the immune responsiveness against ticks
      and tick-borne pathogens. To gain an insight into the naturally acquired
      resistant and susceptible cattle breed against ticks, studies have been conducted
      comparing the incidence of tick infestation on bovine hosts from divergent
      genetic backgrounds. It is well-documented that purebred and crossbred Bos taurus
      indicus cattle are more resistant to ticks and tick-borne pathogens compared to
      purebred European Bos taurus taurus cattle. Genetic studies identifying
      Quantitative Trait Loci markers using microsatellites and SNPs have been
      inconsistent with very low percentages relating phenotypic variation with tick
      infestation. Several skin gene expression and immunological studies have been
      undertaken using different breeds, different samples (peripheral blood, skin with
      tick feeding), infestation protocols and geographic environments. Susceptible
      breeds were commonly found to be associated with the increased expression of toll
      like receptors, MHC Class II, calcium binding proteins, and complement factors
      with an increased presence of neutrophils in the skin following tick feeding.
      Resistant breeds had higher levels of T cells present in the skin prior to tick
      infestation and thus seem to respond to ticks more efficiently. The skin of
      resistant breeds also contained higher numbers of eosinophils, mast cells and
      basophils with up-regulated proteases, cathepsins, keratins, collagens and
      extracellular matrix proteins in response to feeding ticks. Here we review
      immunological and molecular determinants that explore the cattle tick
      Rhipicephalus microplus-host resistance phenomenon as well as contemplating new
      insights and future directions to study tick resistance and susceptibility, in
      order to facilitate interventions for tick control.

PMID- 29322035
TI  - Evolution of Bordetellae from Environmental Microbes to Human Respiratory
      Pathogens: Amoebae as a Missing Link.
AB  - The genus Bordetella comprises several bacterial species that colonize the
      respiratory tract of mammals. It includes B. pertussis, a human-restricted
      pathogen that is the causative agent of Whooping Cough. In contrast, the closely
      related species B. bronchiseptica colonizes a broad range of animals as well as
      immunocompromised humans. Recent metagenomic studies have identified known and
      novel bordetellae isolated from different environmental sources, providing a new
      perspective on their natural history. Using phylogenetic analysis, we have shown
      that human and animal pathogenic bordetellae have most likely evolved from
      ancestors that originated from soil and water. Our recent study found that B.
      bronchiseptica can evade amoebic predation and utilize Dictyostelium discoideum
      as an expansion and transmission vector, which suggests that the evolutionary
      pressure to evade the amoebic predator enabled the rise of bordetellae as
      respiratory pathogens. Interactions with amoeba may represent the starting point
      for bacterial adaptation to eukaryotic cells. However, as bacteria evolve and
      adapt to a novel host, they can become specialized and restricted to a specific
      host. B. pertussis is known to colonize and cause infection only in humans, and
      this specialization to a closed human-to-human lifecycle has involved genome
      reduction and the loss of ability to utilize amoeba as an environmental
      reservoir. The discoveries from studying the interaction of Bordetella species
      with amoeba will elicit a better understanding of the evolutionary history of
      these and other important human pathogens.

PMID- 29322036
TI  - MHC Class II Activation and Interferon-gamma Mediate the Inhibition of
      Neutrophils and Eosinophils by Staphylococcal Enterotoxin Type A (SEA).
AB  - Staphylococcal enterotoxins are classified as superantigens that act by linking T
      cell receptor with MHC class II molecules, which are expressed on classical
      antigen-presenting cells (APC). Evidence shows that MHC class II is also
      expressed in neutrophils and eosinophils. This study aimed to investigate the
      role of MHC class II and IFN-gamma on chemotactic and adhesion properties of
      neutrophils and eosinophils after incubation with SEA. Bone marrow (BM) cells
      obtained from BALB/c mice were resuspended in culture medium, and incubated with
      SEA (3-30 ng/ml; 1-4 h), after which chemotaxis and adhesion were evaluated.
      Incubation with SEA significantly reduced the chemotactic and adhesive responses
      in BM neutrophils activated with IL-8 (200 ng/ml). Likewise, SEA significantly
      reduced the chemotactic and adhesive responses of BM eosinophils activated with
      eotaxin (300 ng/ml). The inhibitory effects of SEA on cell chemotaxis and
      adhesion were fully prevented by prior incubation with an anti-MHC class II
      blocking antibody (2 MUg/ml). SEA also significantly reduced the intracellular
      Ca2+ levels in IL-8- and eotaxin-activated BM cells. No alterations of MAC-1,
      VLA4, and LFA-1alpha expressions were observed after SEA incubation. In addition,
      SEA elevated by 3.5-fold (P < 0.05) the INF-gamma levels in BM cells. Incubation
      of BM leukocytes with IFN-gamma (10 ng/ml, 2 h) reduced both neutrophil and
      eosinophil chemotaxis and adhesion, which were prevented by prior incubation with
      anti-MHC class II antibody (2 MUg/ml). In conclusion, SEA inhibits neutrophil and
      eosinophil by MHC class II-dependent mechanism, which may be modulated by
      concomitant release of IFN-gamma.

PMID- 29322037
TI  - Persistent Bacterial Bronchitis: Time to Venture beyond the Umbrella.
AB  - Chronic cough in children is common and frequently mismanaged. In the past, cough
      was diagnosed as asthma and inappropriate asthma therapies prescribed and
      escalated. It has been realized that persistent bacterial bronchitis (PBB) is a
      common cause of wet cough and responds to oral antibiotics. The initial
      definition comprised a history of chronic wet cough, positive bronchoalveolar
      (BAL) cultures for a respiratory pathogen and response to a 2-week course of oral
      amoxicillin-clavulanic acid. This is now termed PBB-micro; PBB-clinical
      eliminates the need for BAL. PBB-extended is PBB-micro or PBB-clinical but
      resolution necessitating 4 weeks of antibiotics; and recurrent PBB is >3 attacks
      of PBB-micro or-clinical/year. However, the airway has only a limited range of
      responses to chronic inflammation and infection, and neutrophilic airway disease
      is seen in many other conditions, such as cystic fibrosis and primary ciliary
      dyskinesia, both chronic suppurative lung disease endotypes, whose recognition
      has led to huge scientific and clinical advances. There is an urgent need to
      extend endotyping into PBB, especially PBB-recurrent. We need to move from
      associative studies and, in particular, deploy sophisticated modern -omics
      technologies and systems biology, rather as has been done in the context of
      asthma in U-BIOPRED. In summary, the use of the term PBB has done signal service
      in pointing us away from prescribing asthma therapies to children with infected
      airways, but we now need to move beyond a simple description to teasing out
      underlying endotypes.

PMID- 29322038
TI  - Developing and Implementing a Pediatric Emergency Care Curriculum for Providers
      at District Level Hospitals in Sub-Saharan Africa: A Case Study in Kenya.
AB  - Introduction: Emergency medicine is a relatively new field in sub-Saharan Africa
      and dedicated training in pediatric emergency care is limited. While guidelines
      from the African Federation of Emergency Medicine (AFEM) regarding emergency
      training exist, a core curriculum in pediatric emergency care has not yet been
      established for providers at the district hospital level. Methods: The objective
      of the project was to develop a curriculum for providers with limited training in
      pediatric emergencies, and contain didactic and simulation components with
      emphasis on treatment and resuscitation using available resources. A core
      curriculum for pediatric emergency care was developed using a validated model of
      medical education curriculum development and through review of existing
      guidelines and literature. Based on literature review, as well as a review of
      existent guidelines in pediatric and emergency care, 10 core topics were chosen
      and agreed upon by experts in the field, including pediatric and emergency care
      providers in Kenya and the United States. These topics were confirmed to be
      consistent with the principles of emergency care endorsed by AFEM as well as
      complimentary to existing Kenyan medical school syllabi. A curriculum based on
      these 10 core topics was created and subsequently piloted with a group of medical
      residents and clinical officers at a community hospital in western Kenya.
      Results: The 10 core pediatric topics prioritized were airway management,
      respiratory distress, thoracic and abdominal trauma, head trauma and cervical
      spine management, sepsis and shock, endocrine emergencies, altered mental
      status/toxicology, orthopedic emergencies, burn and wound management, and
      pediatric advanced life support. The topics were incorporated into a curriculum
      comprised of ten 1.5-h combined didactic plus low-fidelity simulation modules.
      Feedback from trainers and participating providers gave high ratings to the ease
      of information delivery, relevance, and appropriateness of the curriculum.
      Conclusion: We present here a core curriculum in pediatric emergency care for
      district hospital level providers in Kenya which can be used as a framework for
      further development and implementation of training programs throughout sub
      Saharan Africa.

PMID- 29322039
TI  - Should Australia Ban the Use of Genetic Test Results in Life Insurance?
AB  - Under current Australian regulation, life insurance companies can require
      applicants to disclose all genetic test results, including results from research
      or direct-to-consumer tests. Life insurers can then use this genetic information
      in underwriting and policy decisions for mutually rated products, including life,
      permanent disability, and total income protection insurance. Over the past
      decade, many countries have implemented moratoria or legislative bans on the use
      of genetic information by life insurers. The Australian government, by contrast,
      has not reviewed regulation since 2005 when it failed to ensure implementation of
      recommendations made by the Australian Law Reform Commission. In that time, the
      Australian life insurance industry has been left to self-regulate its use of
      genetic information. As a result, insurance fears in Australia now are leading to
      deterred uptake of genetic testing by at-risk individuals and deterred
      participation in medical research, both of which have been documented. As the
      potential for genomic medicine grows, public trust and engagement are critical
      for successful implementation. Concerns around life insurance may become a
      barrier to the development of genomic health care, research, and public health
      initiatives in Australia, and the issue should be publicly addressed. We argue a
      moratorium on the use of genetic information by life insurers should be enacted
      while appropriate longer term policy is determined and implemented.

PMID- 29322040
TI  - A Technology-Aided Program to Support Basic Occupational Engagement and Mobility
      in Persons with Multiple Disabilities.
AB  - Background: Persons with severe/profound intellectual and multiple disabilities
      tend to be passive and sedentary. Promoting their occupational engagement and
      mobility (i.e., indoor walking) can help to modify their condition and improve
      their environmental input, health, and social image. Aim: This study assessed
      whether a technology-aided program was suitable to (a) support independent
      occupation and mobility in eight participants with intellectual and sensory
      disabilities and (b) eventually increase the participants' heart rates to levels
      considered beneficial for them. Method: The program, which involved a computer
      system regulating the presentation of auditory or visual cues and the delivery of
      preferred stimulation, was introduced according to a non-concurrent multiple
      baseline design across participants. The auditory or visual cues guided the
      participants to collect objects from different desks and to transport them to a
      final destination (i.e., depositing them into a carton). Preferred stimulation
      was available to the participants for collecting and for depositing the objects.
      Results: During the program, all participants had an increase in their
      independent responses of collecting objects and transporting them to the final
      destination. Their heart rates also increased to levels reflecting moderate
      intensity physical exercise, potentially beneficial for their health. Conclusion:
      A program, such as that used in this study, can promote occupational engagement
      and mobility in persons with multiple disabilities.

PMID- 29322041
TI  - A Model to Promote Public Health by Adding Evidence-Based, Empathy-Enhancing
      Programs to All Undergraduate Health-care Curricula.
AB  - Fostering empathy in future health-care providers through service-learning is
      emerging as central to public health promotion. Patients fare better when their
      caregivers have higher relationship-centered characteristics such as the ones
      measured by the Jefferson Scale of Empathy. Unfortunately, these characteristics
      often deteriorate during health-care professional training. Nevertheless, growing
      literature documents how we can promote empathy, and other patient-centered
      characteristics, throughout health-care professional students' undergraduate
      education. As for proven treatment plans, we believe we should also use evidence
      based guidelines to foster relationship-centered characteristics in our students
      when training them to practice as part of an interdisciplinary health-care team.

PMID- 29322042
TI  - Fine-Tuning the Wall Thickness of Ordered Mesoporous Graphene by Exploiting
      Ligand Exchange of Colloidal Nanocrystals.
AB  - Because of their unique physical properties, three-dimensional (3D) graphene has
      attracted enormous attention over the past years. However, it is still a
      challenge to precisely control the layer thickness of 3D graphene. Here, we
      report a novel strategy to rationally adjust the wall thickness of ordered
      mesoporous graphene (OMG). By taking advantage of ligand exchange capability of
      colloidal Fe3O4 nanocrystals, we are able to fine-tune the wall thickness of OMG
      from 2 to 6 layers of graphene. When evaluated as electrocatalyst for oxygen
      reduction reaction upon S and N doping, the 4-layer OMG is found to show better
      catalytic performance compared with their 2- and 6-layer counterparts, which we
      attribute to the enhanced exposure of active sites arising from the thin wall
      thickness and high surface area.

PMID- 29322043
TI  - Dynamic Mechanical Compression of Chondrocytes for Tissue Engineering: A Critical
      Review.
AB  - Articular cartilage functions to transmit and translate loads. In a classical
      structure-function relationship, the tissue resides in a dynamic mechanical
      environment that drives the formation of a highly organized tissue architecture
      suited to its biomechanical role. The dynamic mechanical environment includes
      multiaxial compressive and shear strains as well as hydrostatic and osmotic
      pressures. As the mechanical environment is known to modulate cell fate and
      influence tissue development toward a defined architecture in situ, dynamic
      mechanical loading has been hypothesized to induce the structure-function
      relationship during attempts at in vitro regeneration of articular cartilage.
      Researchers have designed increasingly sophisticated bioreactors with dynamic
      mechanical regimes, but the response of chondrocytes to dynamic compression and
      shear loading remains poorly characterized due to wide variation in study design,
      system variables, and outcome measurements. We assessed the literature pertaining
      to the use of dynamic compressive bioreactors for in vitro generation of
      cartilaginous tissue from primary and expanded chondrocytes. We used specific
      search terms to identify relevant publications from the PubMed database and
      manually sorted the data. It was very challenging to find consensus between
      studies because of species, age, cell source, and culture differences, coupled
      with the many loading regimes and the types of analyses used. Early studies that
      evaluated the response of primary bovine chondrocytes within hydrogels, and that
      employed dynamic single-axis compression with physiologic loading parameters,
      reported consistently favorable responses at the tissue level, with upregulation
      of biochemical synthesis and biomechanical properties. However, they rarely
      assessed the cellular response with gene expression or mechanotransduction
      pathway analyses. Later studies that employed increasingly sophisticated
      biomaterial-based systems, cells derived from different species, and complex
      loading regimes, did not necessarily corroborate prior positive results. These
      studies report positive results with respect to very specific conditions for
      cellular responses to dynamic load but fail to consistently achieve significant
      positive changes in relevant tissue engineering parameters, particularly collagen
      content and stiffness. There is a need for standardized methods and analyses of
      dynamic mechanical loading systems to guide the field of tissue engineering
      toward building cartilaginous implants that meet the goal of regenerating
      articular cartilage.

PMID- 29322044
TI  - Repositioning Titanium: An In Vitro Evaluation of Laser-Generated Microporous,
      Microrough Titanium Templates As a Potential Bridging Interface for Enhanced
      Osseointegration and Durability of Implants.
AB  - Although titanium alloys remain the preferred biomaterials for the manufacture of
      biomedical implants today, such devices can fail within 15 years of implantation
      due to inadequate osseointegration. Furthermore, wear debris toxicity due to
      alloy metal ion release has been found to cause side-effects including
      neurotoxicity and chronic inflammation. Titanium, with its known
      biocompatibility, corrosion resistance, and high elastic modulus, could if
      harnessed in the form of a superficial scaffold or bridging device, resolve such
      issues. A novel three-dimensional culture approach was used to investigate the
      potential osteoinductive and osseointegrative capabilities of a laser-generated
      microporous, microrough medical grade IV titanium template on human skeletal stem
      cells (SSCs). Human SSCs seeded on a rough 90-um pore surface of ethylene oxide
      sterilized templates were observed to be strongly adherent, and to display early
      osteogenic differentiation, despite their inverted culture in basal conditions
      over 21 days. Limited cellular migration across the template surface highlighted
      the importance of high surface wettability in maximizing cell adhesion, spreading
      and cell-biomaterial interaction, while restricted cell ingrowth within the
      conical-shaped pores underlined the crucial role of pore geometry and size in
      determining the extent of osseointegration of an implant device. The overall
      findings indicate that titanium only devices, with appropriate optimizations to
      porosity and surface wettability, could yet play a major role in improving the
      long-term efficacy, durability, and safety of future implant technology.

PMID- 29322047
TI  - The Value Chain Approach in One Health: Conceptual Framing and Focus on Present
      Applications and Challenges.
AB  - The value chain (VC) is a major operational concept for socioeconomic analysis at
      meso level. Widely mobilized in development practice, it is still undergoing
      conceptual and practical refining, e.g., to take account of environmental and
      social sustainability. Briefly, VC refers to a system of value creation through
      the full set of actors, links, technical and commercial activities and flows
      involved in the provision of a good or service on a market. In the past decade,
      this concept has been promoted in the management of animal health. In particular,
      the emergence of highly pathogenic avian influenza (HPAI) has triggered an
      interdisciplinary dynamic including VC analysis as a central tool. These efforts
      promoted participatory investigation methods in the analysis of health systems.
      Using qualitative and quantitative data, these methods acknowledge the usefulness
      of actors' involvement and knowledge, hence facilitating the transdisciplinarity
      needed for effective action. They fit into adaptive and action-oriented
      strategies, fostering stakeholders' participation. Recent research on HPAI
      surveillance in South-East Asia merged VC and participatory approaches to develop
      innovative tools for analyzing constraints to information flow. On-going
      interventions for HPAI prevention and control as well as the prevention of other
      emerging zoonotic risks in Africa are presently building on this VC framework to
      develop strategies for its application at national and regional scales. Based on
      the latter experiences, this article proposes a field-based perspective on VC
      applications to animal and public health systems, within a One Health approach
      responding to the overall challenge of complexity.

PMID- 29322046
TI  - Extracellular Vesicles As Mediators of Cardiovascular Calcification.
AB  - Involvement of cell-derived extracellular particles, coined as matrix vesicles
      (MVs), in biological bone formation was introduced by Bonucci and Anderson in mid
      1960s. In 1983, Anderson et al. observed similar structures in atherosclerotic
      lesion calcification using electron microscopy. Recent studies employing new
      technologies and high- resolution microscopy have shown that although they
      exhibit characteristics similar to MVs, calcifying extracellular vesicles (EVs)
      in cardiovascular tissues are phenotypically distinct from their bone
      counterparts. EVs released from cells within cardiovascular tissues may contain
      either inhibitors of calcification in normal physiological conditions or
      promoters in pathological environments. Pathological conditions characterized by
      mineral imbalance (e.g., atherosclerosis, chronic kidney disease, diabetes) can
      cause smooth muscle cells, valvular interstitial cells, and macrophages to
      release calcifying EVs, which contain specific mineralization-promoting cargo.
      These EVs can arise from either direct budding of the cell plasma membrane or
      through the release of exosomes from multivesicular bodies. In contrast, MVs are
      germinated from specific sites on osteoblast, chondrocyte, or odontoblast
      membranes. Much like MVs, calcifying EVs in the fibrillar collagen extracellular
      matrix of cardiovascular tissues serve as calcification foci, but the mineral
      that forms appears different between the tissues. This review highlights recent
      studies on mechanisms of calcifying EV formation, release, and mineralization in
      cardiovascular calcification. Furthermore, we address the MV-EV relationship, and
      offer insight into therapeutic implications to consider for potential targets for
      each type of mineralization.

PMID- 29322045
TI  - Multiple Duties for Spindle Assembly Checkpoint Kinases in Meiosis.
AB  - Cell division in mitosis and meiosis is governed by evolutionary highly conserved
      protein kinases and phosphatases, controlling the timely execution of key events
      such as nuclear envelope breakdown, spindle assembly, chromosome attachment to
      the spindle and chromosome segregation, and cell cycle exit. In mitosis, the
      spindle assembly checkpoint (SAC) controls the proper attachment to and alignment
      of chromosomes on the spindle. The SAC detects errors and induces a cell cycle
      arrest in metaphase, preventing chromatid separation. Once all chromosomes are
      properly attached, the SAC-dependent arrest is relieved and chromatids separate
      evenly into daughter cells. The signaling cascade leading to checkpoint arrest
      depends on several protein kinases that are conserved from yeast to man. In
      meiosis, haploid cells containing new genetic combinations are generated from a
      diploid cell through two specialized cell divisions. Though apparently less
      robust, SAC control also exists in meiosis. Recently, it has emerged that SAC
      kinases have additional roles in executing accurate chromosome segregation during
      the meiotic divisions. Here, we summarize the main differences between mitotic
      and meiotic cell divisions, and explain why meiotic divisions pose special
      challenges for correct chromosome segregation. The less-known meiotic roles of
      the SAC kinases are described, with a focus on two model systems: yeast and mouse
      oocytes. The meiotic roles of the canonical checkpoint kinases Bub1, Mps1, the
      pseudokinase BubR1 (Mad3), and Aurora B and C (Ipl1) will be discussed. Insights
      into the molecular signaling pathways that bring about the special chromosome
      segregation pattern during meiosis will help us understand why human oocytes are
      so frequently aneuploid.

PMID- 29322048
TI  - Evaluation of Animal-Based Indicators to Be Used in a Welfare Assessment Protocol
      for Sheep.
AB  - Sheep are managed under a variety of different environments (continually
      outdoors, partially outdoors with seasonal or diurnal variation, continuously
      indoors) and for different purposes, which makes assessing welfare challenging.
      This diversity means that resource-based indicators are not particularly useful
      and, thus, a welfare assessment scheme for sheep, focusing on animal-based
      indicators, was developed. We focus specifically on ewes, as the most numerous
      group of sheep present on farm, although many of the indicators may also have
      relevance to adult male sheep. Using the Welfare Quality(r) framework of four
      Principles and 12 Criteria, we considered the validity, reliability, and
      feasibility of 46 putative animal-based indicators derived from the literature
      for these criteria. Where animal-based indicators were potentially unreliably or
      were not considered feasible, we also considered the resource-based indicators of
      access to water, stocking density, and floor slipperiness. With the exception of
      the criteria "Absence of prolonged thirst," we suggest at least one animal-based
      indicator for each welfare criterion. As a minimum, face validity was available
      for all indicators; however, for many, we found evidence of convergent validity
      and discriminant validity (e.g., lameness as measured by gait score, body
      condition score). The reliability of most of the physical and health measures has
      been tested in the field and found to be appropriate for use in welfare
      assessment. However, for the majority of the proposed behavioral indicators
      (lying synchrony, social withdrawal, postures associated with pain,
      vocalizations, stereotypy, vigilance, response to surprise, and human approach
      test), this still needs to be tested. In conclusion, the comprehensive assessment
      of sheep welfare through largely animal-based measures is supported by the
      literature through the use of indicators focusing on specific aspects of sheep
      biology. Further work is required for some indicators to ensure that measures are
      reliable when used in commercial settings.

PMID- 29322049
TI  - Differential Levels of Cecal Colonization by Salmonella Enteritidis in Chickens
      Triggers Distinct Immune Kinome Profiles.
AB  - Salmonella enterica serovar Enteritidis are facultative intracellular bacteria
      that cause disease in numerous species. Salmonella-related infections originating
      from poultry and/or poultry products are a major cause of human foodborne illness
      with S. Enteritidis the leading cause worldwide. Despite the importance of
      Salmonella to human health and chickens being a reservoir, little is known of the
      response to infection within the chicken gastrointestinal tract. Using chicken
      specific kinome immune peptide arrays we compared a detailed kinomic analysis of
      the chicken jejunal immune response in a single line of birds with high and low
      Salmonella loads. Four-day-old chicks were challenged with S. Enteritidis (105
      cfu) and cecal content and a section of jejunum collected at three times: early
      [4-7 days post-infection (dpi)], middle (10-17 dpi), and late (24-37 dpi).
      Salmonella colonization was enumerated and birds with the highest (n = 4) and
      lowest (n = 4) loads at each time were selected for kinomic analyses. Key
      biological processes associated with lower loads of Salmonella clustered around
      immune responses, including cell surface receptor signaling pathway, positive
      regulation of cellular processes, defense response, innate immune response,
      regulation of immune response, immune system process, and regulation of
      signaling. Further evaluation showed specific pathways including chemokine, Jak
      Stat, mitogen activated protein kinase, and T cell receptor signaling pathways
      were also associated with increased resistance. Collectively, these findings
      demonstrate that it is possible to identify key mechanisms and pathways that are
      associated with increased resistance against S. Enteritidis cecal colonization in
      chickens. Therefore, providing a foundation for future studies to identify
      specific proteins within these pathways that are associated with resistance,
      which could provide breeders additional biomarkers to identify birds naturally
      more resistant to this important foodborne pathogen.

PMID- 29322050
TI  - Effects of umeclidinium/vilanterol on exercise endurance in COPD: a randomised
      study.
AB  - This multicentre, randomised, double-blind, placebo-controlled, two-period
      crossover study assessed the effect of umeclidinium/vilanterol (UMEC/VI) on
      exercise capacity in patients with chronic obstructive pulmonary disease (COPD)
      using the endurance shuttle walk test (ESWT). Patients were randomised 1:1 to one
      of two treatment sequences: 1) UMEC/VI 62.5/25 ug followed by placebo or 2)
      placebo followed by UMEC/VI 62.5/25 ug. Each treatment was taken once daily for
      12 weeks. The primary end-point was 3-h post-dose exercise endurance time (EET)
      at week 12. Secondary end-points included trough forced expiratory volume in 1 s
      (FEV1) and 3-h post-dose functional residual capacity (FRC), both at week 12.
      COPD Assessment Test (CAT) score at week 12 was also assessed. UMEC/VI treatment
      did not result in a statistically significant improvement in EET change from
      baseline at week 12 versus placebo (p=0.790). However, improvements were observed
      in trough FEV1 (206 mL, 95% CI 167-246), 3-h post-dose FRC (-346 mL, 95% CI -487
      to -204) and CAT score (-1.07 units, 95% CI -2.09 to -0.05) versus placebo at
      week 12. UMEC/VI did not result in improvements in EET at week 12 versus placebo,
      despite improvements in measures of lung function, hyperinflation and health
      status.

PMID- 29322051
TI  - Genetic Variation of the beta-tubulin Gene of Babesia caballi Strains.
AB  - Background: Equine piroplasmosis is caused by two haemoprotozoan parasites:
      Babesia caballi and Theileria equi. Negative economic impact on international
      trade has been associated to endemic sites. This is the reason why carrier
      detection requires reliable diagnostic methods. Various diagnostic modalities can
      be used alone or in combination including PCR. However, genetic variation of
      commonly used genes is still of debate. The aim of this research was to sequence
      the beta-tubulin gene of a B. caballi strain from Spain and to compare it with
      known beta-tubulin sequences. Methods: DNA was isolated from a cryopreserved
      strain from Spain and acute and chronic carrier horses. Firstly, degenerated
      primer pairs were designed based on GenBank sequences of different Babesia and
      Theileria species for sequencing. The primers were redesigned to amplify both
      parasites, simultaneously. Finally, a species-specific primer pair for B. caballi
      was designed and a Restriction Fragment Length Polymorphism-PCR (PCR-RFLP) assay
      performed to know the difference of known B. caballi strains. Results: We
      provided new insights of the beta-tubulin gene and a good molecular coverage of
      this gene, contributing with a number of useful primers to amplify T. equi and B.
      caballi. Moreover, PCR-RFLP assays based on the exon II of this gene confirmed
      the causative B. caballi strain in Spanish horses. Conclusion: We reported useful
      primer pairs for diagnostic and a new sequence of the beta-tubulin gene of B.
      caballi, which will facilitate the development of future assays and the detection
      of infected horses, preventing thus the spread of this disease worldwide.

PMID- 29322052
TI  - Composition of Anopheles Species Collected from Selected Malarious Areas of
      Afghanistan and Iran.
AB  - Background: Malarious areas in Iran are close to Afghanistan and Pakistan that
      urge the researchers to extend their knowledge on malaria epidemiology to the
      neighboring countries as well. Vectorial capacity differs at species or even at
      population level, the first essential step is accurate identification of vectors.
      This study aimed to identify Anopheles species composition in selected malarious
      areas of Afghanistan and Iran, providing further applied data for other research
      in two countries. Methods: Adults Anopheles spp. were collected from four
      provinces in Afghanistan (Badakhshan, Herat, Kunduz, Nangarhar) by pyrethrum
      spray catch, hand collection methods through WHO/EMRO coordination and from
      Chabahar County in Iran by pyrethrum spray catch method. Identification was
      performed using reliable identification key. Results: Totally, 800 female
      Anopheles mosquitos, 400 from each country were identified at species level.
      Anopheles composition in Afghanistan was An. superpictus, An. stephensi and An.
      hyrcanus. Most prevalent species in Badakhshan and Kunduz were An. superpictus,
      whereas An. stephensi and An. hyrcanus were respectively found in Nangarhar and
      Heart. Anopheles species in Chabahar County of Iran were An. stephensi, An.
      fluviatilis, An. culicifacies and An. sergentii. The most prevalent species was
      An. stephensi. Conclusion: Current study provides a basis for future research
      such as detection of Plasmodium infection in collected samples which is on
      process by the authors, also for effective implementation of evidence-based
      malaria vector intervention strategies.

PMID- 29322053
TI  - Insect Fauna of Human Cadavers in Tehran District.
AB  - Background: Entomological data can provide valuable information for crime scene
      investigations especially in post-mortem interval (PMI) estimation. This study
      performed to determine insect fauna of human corpses in Tehran district. Methods:
      Insect specimens were collected from 12 human cadavers during spring and summer
      2014 and were identified using morphological characteristics. Results: Four fly
      species including two blowflies Chrysomya albiceps and Lucilia sericata
      (Calliphoridae), one flesh fly Sarcophaga argyrostoma (Sarcophagidae), and one
      phorid fly Megaselia scalaris (Phoridae) and a beetle Dermestes maculatus
      (Dermestidae) was observed on the human cadavers. Chrysomya albiceps was the most
      dominant species on the corpses temporally and spatially. Conclusion: Chrysomya
      albiceps was the most dominant insect species on human cadavers in the area study
      spatio-temporally. The data make C. albiceps as a valuable entomological
      indicator for PMI estimation in Tehran and other parts of the country. However,
      further biological and ecological data such as its behavior, life tables, and
      consistent developmental time should be investigated when establishing a PMI in
      the region.

PMID- 29322054
TI  - Spatial Distribution of Medically Important Scorpions in North West of Iran.
AB  - Background: Scorpions are one of the most important medical arthropods in Iran.
      This study aimed to determine the fauna, spatial distribution and some
      morphological characteristics of these venomous arthropods in the study area.
      Methods: Scorpions were collected using Ultra Violet light, rock rolling and
      digging methods in West Azerbaijan, East Azerbaijan, and Ardabil Provinces during
      2015-2016. The specimens were preserved in 75% ethyl alcohol and transferred to
      the laboratory for species identification and morphological studies. Results:
      Distribution maps were produced using ArcGIS 10.3. Totally, 368 specimens from
      two families of Buthidae (97.1%) and Scorpionidae (2.99%) were collected and
      identified as Mesobuthus eupeus (80.16%), Androctonus crassicauda (10.60%), M.
      caucasicus (4.89%), Hottentotta saulcyi (1.35%) and Scorpio maurus (2.99%).
      Conclusion: The presence of medically important species, including the deadly
      black one in northwestern Iran requires health educational and control programs
      for reduction of these public health problems.

PMID- 29322055
TI  - The PCR-RFLP-Based Detection and Identification of the Leishmania Species Causing
      Human Cutaneous Leishmaniasis in the Khorasan-Razavi Province, Northeast of Iran.
AB  - Background: Leishmania tropica, the causative agent of anthroponotic cutaneous
      leishmaniasis (ACL), and Leishmania major, which causes zoonotic cutaneous
      leishmaniasis (ZCL), are endemic in Iran. Methods: Cross-sectional study was
      designed to identify Leishmania species in cutaneous leishmaniasis patients who
      referred to Mashhad Health Centers from 2013 to 2014 using ITS-PCR-RFLP
      technique. First, physical examinations were performed in all suspected patients
      and CL cases were confirmed with microscopical examinations. A questionnaire was
      prepared and completed for each confirmed patient and DNA from each lesion smear
      was extracted, separately. The ribosomal internal transcribed spacer was
      amplified with appropriate primers and PCR products were digested by enzyme Taq1
      restrict enzyme. Results: From all patients, 51 cases (54.3%) were men and 43 of
      them (45.7%) were women. The most frequent age group was 20-29 years old (27.2%).
      Hands, face and feet were the most common sites for appearance of skin lesions.
      All of the 94 cases (100%) tested found to be positive by ITS-PCR-RFLP. Overall,
      Leishmania species were identified in all of the 94 lesion smears which 33 (35%)
      of them were L. major and 61 (65%) of the remained isolates were identified L.
      tropica. Conclusion: Characterization of Leishmania isolates collected from
      different parts of Khorasan-Razavi Province showed that L. tropica is predominant
      agents of CL, especially in large and medium sized cities such as Mashhad and
      Shandiz. Moreover, this study revealed that ITS-PCR-RFLP based on our designed
      primers is a suitable method for species characterization.

PMID- 29322056
TI  - Field Evaluation of Outdoor Ultra-Low Volume (ULV) Applications against
      Phlebotomine Sand Flies (Diptera: Psychodidae) in Al Rabta, North-West of Libya.
AB  - Background: Al Rabta is a rural area in the North-West of Libya that represents
      an important focus of zoonotic cutaneous leishmaniasis. This study aimed to
      evaluate the effect of Ultra Low Volume (ULV) applications in controlling sand
      flies and its impact on leishmaniasis transmission in this area. Methods: Two
      neighboring villages were selected: Al Rabta West (RW) as cypermethrin treated
      village and Al Rabta East (RE) as check one. The ULV was evaluated through 3
      spraying cycles during Apr, Jun and Sep 2013. In the two villages, a number of
      outdoor sites were selected for sampling of sand flies (twice a month) using the
      CDC light traps. The cases of CL reported in the two villages during the study
      period were obtained from Al Rabta health center. Results: The two villages were
      similar where 9 species of sand flies (6 of Phlebotomu and 3 of Sergentomyia)
      were collected of which S. minuta and P. papatasi were the abundant species. As
      compared to the pre- ULV spraying, during the post- spraying periods: i) the
      reduction in abundance of the different species ranged from 20.85 to 77.52% with
      46.69% as an overall reduction for all species altogether and, ii) in
      significantly (P> 0.05) higher mean ratio of males: females for all species
      altogether (1:2.41). Moreover, ULV spraying resulted in the absence of CL
      (Leishmania major) cases (Passive Case Detection). Conclusion: The efficiency of
      ULV spraying in reducing sand fly population, CL cases and consequently limits
      the disease transmission.

PMID- 29322057
TI  - Epidemiological Study on Cutaneous Leishmaniasis in an Endemic Area, of Qom
      Province, Central Iran.
AB  - Background: Cutaneous leishmaniasis (CL) is one of the most important health
      problems in many areas of Iran. There are two forms of the disease in Iran,
      anthroponotic and zoonotic CL. This study conducted to assess the epidemiological
      situation of CL in an endemic area of Qom Province, central Iran from Apr to Nov
      2015. Methods: The sticky paper traps and aspirating tubes were used for
      collecting adult sand flies. Sherman traps and small insect nets were used to
      capture rodents and small mammals. Giemsa staining was used for preparing the
      expanded smear and followed by PCR for identifying the causative agent in human,
      vectors, and reservoirs. In this study, relative frequency of CL was also
      calculated. Results: Fourteen species of Phlebotomine sand flies were collected.
      Phlebotomus papatasi (61.74%) was the predominant species through the period of
      activity. Overall, 62 Meriones libycus, 8 Nesokia indica, 4 Mus musculus, 16
      Allactaga elater and 2 Hemiechinus auritis were caught. PCR technique showed 6
      out of 150 P. papatasi (2%), two out of 62 M. libycus (3.23%) and all of
      suspected human's skin tissue samples (100%) were infected with Leishmania major.
      The relative frequency of CL was 0.30%. Conclusion: This is the first detection
      of L. major within P. papatasi, M. libycus and human in Kahak District in Qom
      Province of Iran. Zoonotic cycle of CL exists in this area, L. major is the
      causative agent, P. papatasi is the main vector and M. libycus is the main
      reservoir of the disease.

PMID- 29322059
TI  - Citrus Seed Oils Efficacy against Larvae of Aedes aegypti.
AB  - Background: Dengue fever is a serious public health issue in Pakistan for many
      years. Globally plants have been reported to contain compounds with insecticidal
      properties. These properties have been demonstrated more recently on the larval
      stages of mosquitoes. Therefore, Citrus cultivar seeds were evaluated for
      larvicidal potential against the primary dengue vector Aedes aegypti. Methods:
      Extraction of oil was done by a steam distillation method and oils were evaluated
      according to WHO guidelines for larvicides 2005 for evaluation of insecticidal
      properties of citrus seed extracts against mosquito larvae. Result: Among the
      Citrus cultivar seed oil, rough lemon (Citrus jambhiri) had the lowest LC50 value
      (200.79ppm), while musambi (C. sinensis var musambi) had the highest LC50 value
      (457.30ppm) after 24 h of exposure. Conclusion: Citrus cultivars have some
      larvicidal potential but C. jambhiri had the greatest potential against A.
      aegypti larvae. Further small-scale field trials using the extracts of C.
      jambhiri will be conducted to determine operational feasibility.

PMID- 29322058
TI  - Gas Chromatography, GC/Mass Analysis and Bioactivity of Essential Oil from Aerial
      Parts of Ferulago trifida: Antimicrobial, Antioxidant, AChE Inhibitory, General
      Toxicity, MTT Assay and Larvicidal Activities.
AB  - Background: We aimed to investigate different biological properties of aerial
      parts essential oil of Ferulago trifida Boiss and larvicidal activity of its
      volatile oils from all parts of plant. Methods: Essential oil was prepared by
      steam distillation and analyzed by Gas chromatography and GC/Mass. Antioxidant,
      antimicrobial, cytotoxic effects and AChE inhibitory of the oil were investigated
      using DPPH, disk diffusion method, MTT assay and Ellman methods. Larvicidal
      activity of F. trifida essential oil against malaria vector Anopheles stephensi
      was carried out according to the method described by WHO. Results: In GC and
      GC/MS analysis, 58 compounds were identified in the aerial parts essential oil,
      of which E-verbenol (9.66%), isobutyl acetate (25.73%) and E-beta-caryophyllene
      (8.68%) were main compounds. The oil showed (IC50= 111.2MUg/ml) in DPPH and IC50=
      21.5 mg/ml in the investigation of AChE inhibitory. Furthermore, the oil
      demonstrated toxicity with (LD50= 1.1MUg/ml) in brine shrimp lethality test and
      with (IC50= 22.0, 25.0 and 42.55 MUg/ml) on three cancerous cell lines (MCF-7, A
      549 and HT-29) respectively. LC50 of stem, root, aerial parts, fruits, and
      flowers essential oils against larvae of An. stephensi were equal with 10.46,
      22.27, 20.50, 31.93 and 79.87ppm respectively. In antimicrobial activities,
      essential oil was effective on all specimens except Escherichia coli, Aspergillus
      niger and Candida albicans. Conclusion: The essential oil showed moderate
      antioxidant activity, strong antimicrobial properties and good toxic effect in
      brine shrimp test and MTT assay on three cancerous cell lines.

PMID- 29322060
TI  - Geographical Distribution of Scorpion Odontobuthus doriae in Isfahan Province,
      Central Iran.
AB  - Background: Scorpions are among the world's venomous arthropods, they sting
      humans every year, suffering painful symptoms or losing their lives because of
      the venom. Odontobuthus doriae Thorell 1876 (Arachnida: Scorpionida: Buthidae) is
      a scorpion of medical importance and therefore its geographical distribution in
      Isfahan Province has been studied. Methods: This descriptive cross-sectional
      study was designed between Mar and Jun in 2012 and 2013 in Province of Isfahan,
      central Iran. Overall, 164 O. doriae scorpions were collected from their natural
      habitat by identifying the dug burrows. This arthropod's burrows were identified
      based on the presence of tumuli, particularly between May and Jun at the sloping
      foothills of pristine embankments. The sampling data was categorized and
      compared. Results: The relative frequency of collected O. doriae for the counties
      was Mobarakeh (13.5%), Shahinshahre (11.5%), Borkhar (9%), Shahreza (7.5%),
      Kashan (7.5%), Naeen (6%), Natanz (5.5%), Isfahan (4.8%), Najafabad (4.8%), Aran
      and Bidgol (4.8%), Dehaghan (4.8%), Flavarjan (3.7%), Khomeinishahr (3.7%), Tiran
      (3.7%), Golpayegan (3.7%), Ardestan (3.7%) and Lenjan (2.5%). No O. doriae was
      collected from other counties of the province. Conclusion: The habitats of O.
      doriae are more often located in central, eastern and northern regions of the
      province compared to other regions. Counties of southern and western regions are
      among cold parts of the province.

PMID- 29322061
TI  - Histopathological Study of Esophageal Infection with Gasterophilus pecorum
      (Diptera: Oestridae) in Persian Onager (Equus hemionus onager).
AB  - Background: The larval stages of Gasterophilus are obligate parasites in the
      gastrointestinal tract of equine accountable for pathologic ulcers in the Persian
      onager gastrointestinal. The aim of the current report was to study the
      histopathological change with G. pecorum larvae in the esophagus of a Persian
      onager. Methods: This study was performed in Iranian Zebra propagation and
      breeding site in Khartouran National Park, southeast of Shahrud City, Semnan
      Province, Iran in 2014. Following a necropsy with specific refer to esophagus of
      one adult female Persian onager were transmitted to the laboratory. After
      autopsy, parasites collected from the esophagus were transmitted into 70%
      alcohol. For histopathological investigation, tissue samples were collected from
      the esophagus. The tissues were fixed in 10% buffered formalin, and conformity
      routine processing, there were stained with Hematoxylin and eosin. Results: After
      clarity by lactophenol parasites were identified as G. pecorum. Microscopic
      recognition contained hyperemia, inflammatory cell infiltration, epithelial
      destruction, esophageal gland hyperplasia. Conclusion: This is the first survey
      of G. pecorum and histopathological study in the Persian onager esophagus in the
      world.

PMID- 29322063
TI  - Neurological Sequelae of Adult Meningitis in Africa: A Systematic Literature
      Review.
AB  - The high human immunodeficiency virus (HIV) prevalence in sub-Saharan Africa has
      markedly changed the epidemiology and presentation of adult meningitis. We
      conducted a systematic review using PubMed, Embase, Ovid, CENTRAL, and African
      Index Medicus to identify studies in Africa with data on neurological outcomes in
      adults after meningitis. We found 22 articles meeting inclusion criteria. From 4
      studies with predominately pneumococcal meningitis, a median of 19% of survivors
      experienced hearing loss up to 40 days. Two studies of cryptococcal meningitis
      evaluated 6- to 12-month outcomes; in one, 41% of survivors had global
      neurocognitive impairment and 20% severe impairment at 1 year, and in a second
      30% of survivors had intermediate disability and 10% severe disability at 6
      months. A single small study of patients with tuberculosis/HIV found marked
      disability in 20% (6 of 30) at 9 months. Despite the high burden of meningitis in
      sub-Saharan Africa, little is known about neurological outcomes of patients with
      HIV-associated meningitides.

PMID- 29322064
TI  - Sexual Orientation Trends and Disparities in School Bullying and Violence-Related
      Experiences, 1999-2013.
AB  - Numerous recent studies have demonstrated that schools are often unsafe for
      lesbian, gay, and bisexual (LGB) adolescents, who are more likely than
      heterosexual peers to be bullied, harassed, or victimized in school contexts.
      Virtually all of these studies call for change, yet none investigate whether or
      not it has occurred. Using repeated waves of a population-based high school
      survey, we examine (1) the extent to which sexual orientation differences in
      school bullying and violence-related experiences are reported by lesbian/gay,
      bisexual, and heterosexual male and female adolescents; (2) trends in school
      bullying and violence-related experiences for each gender/orientation group, and
      (3) whether disparities have changed over time. Data were drawn from eight
      Massachusetts biennial Youth Risk Behavior Surveys from 1999 to 2013, grouped
      into 4 waves totaling 24,845 self-identified heterosexual, 270 lesbian/gay, and
      857 bisexual youth. Disparities between LGB and heterosexual peers were found in
      all indicators. Heterosexual youth and gay males saw significant reductions in
      every outcome between the first and last waves. Among bisexual males, skipping
      school due to feeling unsafe, carrying weapons in school, and being bullied all
      decreased, but among lesbians and bisexual females only fighting in school
      declined significantly. Improvement trends in school safety were more consistent
      for heterosexual youth and gay males than for bisexual or lesbian females.
      Notably, despite these improvements, almost no reduction was seen in sexual
      orientation disparities. Future research should identify influences leading to
      reduced school victimization, especially focusing on ways of eliminating
      persistent sexual orientation disparities. Future research should identify
      influences leading to reduced school victimization, especially focusing on ways
      of eliminating persistent sexual orientation disparities.

PMID- 29322066
TI  - Special Section Guest Editorial: Radiomics and Deep Learning.
AB  - This guest editorial introduces and summarizes the JMI Special Section on
      Radiomics and Deep Learning.

PMID- 29322065
TI  - Modeling Anti-HIV-1 HSPC-Based Gene Therapy in Humanized Mice Previously Infected
      with HIV-1.
AB  - Investigations of anti-HIV-1 human hematopoietic stem/progenitor cell (HSPC)
      based gene therapy have been performed by HIV-1 challenge after the engraftment
      of gene-modified HSPCs in humanized mouse models. However, the clinical
      application of gene therapy is to treat HIV-1-infected patients. Here, we
      developed a new method to investigate an anti-HIV-1 HSPC-based gene therapy in
      humanized mice previously infected with HIV-1. First, humanized mice were
      infected with HIV-1. When plasma viremia reached >107 copies/mL 3 weeks after HIV
      1 infection, the mice were myeloablated with busulfan and transplanted with anti
      HIV-1 gene-modified CD34+ HSPCs transduced with a lentiviral vector expressing
      two short hairpin RNAs (shRNAs) against CCR5 and HIV-1 long terminal repeat
      (LTR), along with human thymus tissue under the kidney capsule. Anti-HIV-1 vector
      modified human CD34+ HSPCs successfully repopulated peripheral blood and lymphoid
      tissues in HIV-1 previously infected humanized mice. Anti-HIV-1 shRNA vector
      modified CD4+ T lymphocytes showed selective advantage in HIV-1 previously
      infected humanized mice. This new method will be useful for investigations of
      anti-HIV-1 gene therapy when testing in a more clinically relevant experimental
      setting.

PMID- 29322062
TI  - Increased Indoleamine-2,3-Dioxygenase Activity Is Associated With Poor Clinical
      Outcome in Adults Hospitalized With Influenza in the INSIGHT FLU003Plus Study.
AB  - Background: Indoleamine-2,3-dioxygenase (IDO) mediated tryptophan (TRP) depletion
      has antimicrobial and immuno-regulatory effects. Increased kynurenine (KYN)-to
      TRP (KT) ratios, reflecting increased IDO activity, have been associated with
      poorer outcomes from several infections. Methods: We performed a case-control
      (1:2; age and sex matched) analysis of adults hospitalized with influenza
      A(H1N1)pdm09 with protocol-defined disease progression (died/transferred to
      ICU/mechanical ventilation) after enrollment (cases) or survived without
      progression (controls) over 60 days of follow-up. Conditional logistic regression
      was used to analyze the relationship between baseline KT ratio and other
      metabolites and disease progression. Results: We included 32 cases and 64
      controls with a median age of 52 years; 41% were female, and the median durations
      of influenza symptoms prior to hospitalization were 8 and 6 days for cases and
      controls, respectively (P = .04). Median baseline KT ratios were 2-fold higher in
      cases (0.24 mM/M; IQR, 0.13-0.40) than controls (0.12; IQR, 0.09-0.17; P <=
      .001). When divided into tertiles, 59% of cases vs 20% of controls had KT ratios
      in the highest tertile (0.21-0.84 mM/M). When adjusted for symptom duration, the
      odds ratio for disease progression for those in the highest vs lowest tertiles of
      KT ratio was 9.94 (95% CI, 2.25-43.90). Conclusions: High KT ratio was associated
      with poor outcome in adults hospitalized with influenza A(H1N1)pdm09. The
      clinical utility of this biomarker in this setting merits further exploration.
      ClinicalTrialsgov Identifier: NCT01056185.

PMID- 29322067
TI  - Combining multiparametric MRI with receptor information to optimize prediction of
      pathologic response to neoadjuvant therapy in breast cancer: preliminary results.
AB  - Pathologic complete response following neoadjuvant therapy (NAT) is used as a
      short-term surrogate marker of eventual outcome in patients with breast cancer.
      Analyzing voxel-level heterogeneity in MRI-derived parametric maps, obtained
      before and after the first cycle of NAT ([Formula: see text]), in conjunction
      with receptor status, may improve the predictive accuracy of tumor response to
      NAT. Toward that end, we incorporated two MRI-derived parameters, the apparent
      diffusion coefficient and efflux rate constant, with receptor status in a
      logistic ridge-regression model. The area under the curve (AUC) and Brier score
      of the model computed via 10-fold cross validation were 0.94 (95% CI: 0.85, 0.99)
      and 0.11 (95% CI: 0.06, 0.16), respectively. These two statistics strongly
      support the hypothesis that our proposed model outperforms the other models that
      we investigated (namely, models without either receptor information or voxel
      level information). The contribution of the receptor information was manifested
      by an 8% to 15% increase in AUC and a 14% to 21% decrease in Brier score. These
      data indicate that combining multiparametric MRI with hormone receptor status has
      a high likelihood of improved prediction of pathologic response to NAT in breast
      cancer.

PMID- 29322068
TI  - Measuring temporal stability of positron emission tomography standardized uptake
      value bias using long-lived sources in a multicenter network.
AB  - Positron emission tomography (PET) is a quantitative imaging modality, but the
      computation of standardized uptake values (SUVs) requires several instruments to
      be correctly calibrated. Variability in the calibration process may lead to
      unreliable quantitation. Sealed source kits containing traceable amounts of
      [Formula: see text] were used to measure signal stability for 19 PET scanners at
      nine hospitals in the National Cancer Institute's Quantitative Imaging Network.
      Repeated measurements of the sources were performed on PET scanners and in dose
      calibrators. The measured scanner and dose calibrator signal biases were used to
      compute the bias in SUVs at multiple time points for each site over a 14-month
      period. Estimation of absolute SUV accuracy was confounded by bias from the solid
      phantoms' physical properties. On average, the intrascanner coefficient of
      variation for SUV measurements was 3.5%. Over the entire length of the study,
      single-scanner SUV values varied over a range of 11%. Dose calibrator bias was
      not correlated with scanner bias. Calibration factors from the image metadata
      were nearly as variable as scanner signal, and were correlated with signal for
      many scanners. SUVs often showed low intrascanner variability between successive
      measurements but were also prone to shifts in apparent bias, possibly in part due
      to scanner recalibrations that are part of regular scanner quality control.
      Biases of key factors in the computation of SUVs were not correlated and their
      temporal variations did not cancel out of the computation. Long-lived sources and
      image metadata may provide a check on the recalibration process.

PMID- 29322069
TI  - Method comparison for cardiac image registration of coronary computed tomography
      angiography and 3-D echocardiography.
AB  - Treatment decision for coronary artery disease (CAD) is based on both
      morphological and functional information. Image fusion of coronary computed
      tomography angiography (CCTA) and three-dimensional echocardiography (3DE) could
      combine morphology and function into a single image to facilitate diagnosis.
      Three semiautomatic feature-based methods for CCTA/3DE registration were
      implemented and applied on CAD patients. Methods were verified and compared using
      landmarks manually identified by a cardiologist. All methods were found feasible
      for CCTA/3DE fusion.

PMID- 29322070
TI  - Fuzzy c-means segmentation of major vessels in angiographic images of stroke.
AB  - Patients suffering from ischemic stroke develop varying degrees of pial arterial
      supply (PAS), which can affect patient response to reperfusion therapy and risk
      of hemorrhage. Since vessel segmentation may be an important part in identifying
      PAS, we present a fuzzy c-means (FCM) clustering method to segment major vessels
      in x-ray angiograms. Our approach consists of semiautomatic region of interest
      (ROI) delineation, separation of major vessels from capillary blush and/or
      background noise through FCM clustering, and identification of the major vessel
      category. This method was applied to a database of x-ray angiograms of 24
      patients acquired at various frame rates. The ground truth for performance
      evaluation was the designation by an expert radiologist selecting image pixels as
      being vessel or nonvessel. From receiver operating characteristic (ROC) analysis,
      area under the ROC curve (AUC) was the performance metric in the task of
      distinguishing between major vessels and blush or background. When clustering
      data into three categories and performing FCM segmentation on each ROI
      separately, the AUC was 0.89 for the entire database and [Formula: see text] for
      all examined frame-rates. In conclusion, our method showed promising performance
      in identifying major vessels and is anticipated to become an integral part of
      automatic quantification of PAS.

PMID- 29322071
TI  - Algorithm development for intrafraction radiotherapy beam edge verification from
      Cherenkov imaging.
AB  - Imaging of Cherenkov light emission from patient tissue during fractionated
      radiotherapy has been shown to be a possible way to visualize beam delivery in
      real time. If this tool is advanced as a delivery verification methodology, then
      a sequence of image processing steps must be established to maximize accurate
      recovery of beam edges. This was analyzed and developed here, focusing on the
      noise characteristics and representative images from both phantoms and patients
      undergoing whole breast radiotherapy. The processing included temporally
      integrating video data into a single, composite summary image at each control
      point. Each image stack was also median filtered for denoising and ultimately
      thresholded into a binary image, and morphologic small hole removal was used.
      These processed images were used for day-to-day comparison computation, and
      either the Dice coefficient or the mean distance to conformity values can be used
      to analyze them. Systematic position shifts of the phantom up to 5 mm approached
      the observed variation values of the patient data. This processing algorithm can
      be used to analyze the variations seen in patients being treated concurrently
      with daily Cherenkov imaging to quantify the day-to-day disparities in delivery
      as a quality audit system for position/beam verification.

PMID- 29322072
TI  - Plan in 2-D, execute in 3-D: an augmented reality solution for cup placement in
      total hip arthroplasty.
AB  - Reproducibly achieving proper implant alignment is a critical step in total hip
      arthroplasty procedures that has been shown to substantially affect patient
      outcome. In current practice, correct alignment of the acetabular cup is verified
      in C-arm x-ray images that are acquired in an anterior-posterior (AP) view.
      Favorable surgical outcome is, therefore, heavily dependent on the surgeon's
      experience in understanding the 3-D orientation of a hemispheric implant from 2-D
      AP projection images. This work proposes an easy to use intraoperative component
      planning system based on two C-arm x-ray images that are combined with 3-D
      augmented reality (AR) visualization that simplifies impactor and cup placement
      according to the planning by providing a real-time RGBD data overlay. We evaluate
      the feasibility of our system in a user study comprising four orthopedic surgeons
      at the Johns Hopkins Hospital and report errors in translation, anteversion, and
      abduction as low as 1.98 mm, 1.10 deg, and 0.53 deg, respectively. The promising
      performance of this AR solution shows that deploying this system could eliminate
      the need for excessive radiation, simplify the intervention, and enable
      reproducibly accurate placement of acetabular implants.

PMID- 29322074
TI  - Data supporting the understanding of modulatory function of opioid analgesics in
      mouse macrophage activity.
AB  - The data presented herein expand the current understanding of the modulatory
      function of opioid drugs in mouse macrophage activity described in our relevant
      research article (Filipczak-Bryniarska et al., 2017) [1], in which we
      characterize the influence of morphine, buprenorphine and oxycodone on humoral
      and cell-mediated immune response in mice. Among other things, we have shown the
      effects of treatment with assayed analgesics on macrophage ability to induce
      antigen-specific B-cell response to sheep red blood cells as well as to generate
      reactive oxygen intermediates and nitric oxide. The current data demonstrate the
      effects of morphine, buprenorphine or oxycodone administration on phagocytosis of
      sheep red blood cells and zymosan by mouse macrophages, supplementing the data on
      immune modulatory capacities of assayed drugs, recently reported by us (Filipczak
      Bryniarska et al., 2017; Kozlowski et al., 2017) [1,2].

PMID- 29322073
TI  - High-fat/high-sucrose diet results in higher bone mass in aged rats.
AB  - Intake of high-fat/high-sucrose (HFS) diet or high fat diet influences bone
      metabolism in young rodents, but its effects on bone properties of aged rodents
      still remain unclear. This study aimed to examine the effects of HFS diet intake
      on trabecular bone architecture (TBA) and cortical bone geometry (CBG) in aged
      rats. Fifteen male Wistar rats over 1 year were randomly divided into two groups.
      One group was fed a standard laboratory diet (SLD) and the other group was fed a
      HFS diet for six months. The femur/tibia, obtained from both groups at the end of
      experimental period, were scanned by micro-computed tomography for TBA/CBG
      analyses. Serum biochemical analyses were also conducted. Body weight was
      significantly higher in the HFS group than in the SLD group. In both femur and
      tibia, the HFS group showed higher trabecular/cortical bone mass in reference to
      bone mineral content, volume bone mineral density and TBA/CBG parameters compared
      with the SLD group. In addition, serum calcium, inorganic phosphorus, total
      protein, triacylglycerol, HDL and TRACP-5b levels were significantly higher in
      the HFS group than in the SLD group. There were good correlations between body
      weight and bone parameters in the femur and tibia. These results suggest that HFS
      diet intake results in higher bone mass in aged rats. Such effects of HFS diet
      intake might have been induced by increased body weight.

PMID- 29322075
TI  - Data about knowledge and tendency towards organic foods use in Tehran.
AB  - Improper use of chemical fertilizer and pesticide poses not only threats to the
      environmental safety but also major public health issues globally. The adverse
      effects of chemical fertilizers and pesticides forced agricultural scientist to
      look for safer methods such as organic farming. This study was aimed at assessing
      the knowledge and tendency towards organic foods use among people of living in a
      megacity, Tehran. Data was collected from "fall exhibition" and "health food
      exhibition" participants using pretested questionnaire. Data were entered,
      cleaned and analyzed by SPSS version 17. T-test, ANOVA and Regression analysis
      were carried out and the association was considered significant at p-value less
      than 0.05. A total of 400 respondents participated in the study, making a
      response rate of 100%. There were reverse relation between knowledge and
      accessibility and positive relation between trust, marriage and gender and no
      relation with price. Building trust in consumer, and allocation of a special
      label, known logos and ways to track most of the products sold as organic foods
      seems necessary for increasing consumption.

PMID- 29322076
TI  - A spline-based regression parameter set for creating customized DARTEL MRI brain
      templates from infancy to old age.
AB  - This dataset contains the regression parameters derived by analyzing segmented
      brain MRI images (gray matter and white matter) from a large population of
      healthy subjects, using a multivariate adaptive regression splines approach. A
      total of 1919 MRI datasets ranging in age from 1-75 years from four publicly
      available datasets (NIH, C-MIND, fCONN, and IXI) were segmented using the CAT12
      segmentation framework, writing out gray matter and white matter images
      normalized using an affine-only spatial normalization approach. These images were
      then subjected to a six-step DARTEL procedure, employing an iterative non-linear
      registration approach and yielding increasingly crisp intermediate images. The
      resulting six datasets per tissue class were then analyzed using multivariate
      adaptive regression splines, using the CerebroMatic toolbox. This approach allows
      for flexibly modelling smoothly varying trajectories while taking into account
      demographic (age, gender) as well as technical (field strength, data quality)
      predictors. The resulting regression parameters described here can be used to
      generate matched DARTEL or SHOOT templates for a given population under study,
      from infancy to old age. The dataset and the algorithm used to generate it are
      publicly available at https://irc.cchmc.org/software/cerebromatic.php.

PMID- 29322077
TI  - Near infrared hyperspectral dataset of healthy and infected apple tree leaves
      images for the early detection of apple scab disease.
AB  - This dataset presents two series of hyperspectral images of healthy and infected
      apple tree leaves acquired daily, from two days after inoculation until an
      advanced stage of infection (11 days after inoculation). The hyperspectral images
      were calibrated by reflection correction and registered to match the geometry of
      one reference image. On the last experiment day, scab positions are provided.

PMID- 29322078
TI  - Received signal strength and local terrain profile data for radio network
      planning and optimization at GSM frequency bands.
AB  - The behaviour of radio wave signals in a wireless channel depends on the local
      terrain profile of the propagation environments. In view of this, Received Signal
      Strength (RSS) of transmitted signals are measured at different points in space
      for radio network planning and optimization. However, these important data are
      often not publicly available for wireless channel characterization and
      propagation model development. In this data article, RSS data of a commercial
      base station operating at 900 and 1800 MHz were measured along three different
      routes of Lagos-Badagry Highway, Nigeria. In addition, local terrain profile data
      of the study area (terrain elevation, clutter height, altitude, and the distance
      of the mobile station from the base station) are extracted from Digital Terrain
      Map (DTM) to account for the unique environmental features. Statistical analyses
      and probability distributions of the RSS data are presented in tables and graphs.
      Furthermore, the degree of correlations (and the corresponding significance)
      between the RSS and the local terrain parameters were computed and analyzed for
      proper interpretations. The data provided in this article will help radio network
      engineers to: predict signal path loss; estimate radio coverage; efficiently
      reuse limited frequencies; avoid interferences; optimize handover; and adjust
      transmitted power level.

PMID- 29322079
TI  - Fibroblast and keratinocyte gene expression following exposure to extracts of
      neem plant (Azadirachta indica).
AB  - This data article provides gene expression profiles, determined by using real
      time PCR, of fibroblasts and keratinocytes treated with 0.01% and 0.001% extracts
      of neem plant (Azadirachta indica), local name "Kohomba" in Sri Lanka, harvested
      in Sri Lanka. For fibroblasts, the dataset includes expression profiles for genes
      encoding hyaluronan synthase 1 (HAS1), hyaluronan synthase 2 (HAS2),
      hyaluronidase-1 (HYAL1), hyaluronidase-2 (HYAL2), versican, aggrecan, CD44,
      collagen, type I, alpha 1 (COL1A1), collagen, type III, alpha 1 (COL3A1),
      collagen, type VII, alpha 1 (COL7A1), matrix metalloproteinase 1 (MMP1), acid
      ceramidase, basic fibroblast growth factor (bFGF), fibroblast growth factor-7
      (FGF7), vascular endothelial growth factor (VEGF), interleukin-1 alpha (IL
      1alpha), cyclooxygenase-2 (cox2), transforming growth factor beta (TGF-beta), and
      aquaporin 3 (AQP3). For keratinocytes, the expression profiles are for genes
      encoding HAS1, HAS2, HYAL1, HYAL2, versican, CD44, IL-1alpha, cox2, TGF-beta,
      AQP3, Laminin5, collagen, type XVII, alpha 1 (COL17A1), integrin alpha-6 (ITGA6),
      ceramide synthase 3 (CERS3), elongation of very long chain fatty acids protein 1
      (ELOVL1), elongation of very long chain fatty acids protein 4 (ELOVL4), filaggrin
      (FLG), transglutaminase 1 (TGM1), and keratin 1 (KRT1). The expression profiles
      are provided as bar graphs.

PMID- 29322080
TI  - Data on a single oral dose of camu camu (Myrciaria dubia) pericarp extract on
      flow-mediated vasodilation and blood pressure in young adult humans.
AB  - This data article describes the flow-mediated vasodilation (FMD) responses,
      represented by changes in arterial diameter, and blood pressure changes in young
      adults after a single oral dose of camu camu (Myrciaria dubia) pericarp extract
      or placebo (cross-over design). Ten healthy men and 10 healthy women participated
      in this study. Ultrasonic diagnostic equipment was used to monitor arterial
      diameter changes, indicative of FMD, for 110 s after the administration of the
      camu camu extract or placebo. In addition, the systolic and diastolic blood
      pressure values were recorded.

PMID- 29322081
TI  - Data of expression status of miR- 29a and its putative target mitochondrial
      apoptosis regulatory gene DRP1 upon miR-15a and miR-214 inhibition.
AB  - Data is about the mitochondrial apoptosis regulatory framework genes PUMA, DRP1
      (apoptotic), and ARC (anti-apoptotic) analysis after the employment of their
      controlling miRNAs inhibitors. The data represents putative conserved targeting
      of seed regions of miR-15a, miR-29a, and miR-214 with respective target genes
      PUMA, DRP1, and ARC. Data is of cross interference in expression levels of one
      miRNA family, miR-29a and its putative target DRP1 upon the inhibitory treatment
      of other miRNAs 15a and 214.

PMID- 29322082
TI  - Data on microbial and physiochemical characteristics of inlet and outlet water
      from household water treatment devices in Rasht, Iran.
AB  - In this research, we measured various parameters related to drinking water
      quality include turbidity, temperature, pH, EC, TDS, Alkalinity, fecal and total
      coliform, heterotrophic plate count (HPC), free chlorine, Mn, Ca, Mg, Fe, Na, Cl
      , F-, HCO3, in the inlet and outlet of household water treatment devices
      according to the standard methods for the examination of water and wastewater
      (W.E. Federation and Association and A.P.H., 2005) [1]. Sixty four inlet and
      outlet water samples were taken from thirty two household water treatment devices
      from eight different residential blocks in Golsar town of Rasht, Iran. The data
      obtained from experiments were analyzed using the software Special Package for
      Social Sciences (SPSS 24) and MS-Excel.

PMID- 29322083
TI  - Dataset of coded handwriting features for use in statistical modelling.
AB  - The data presented here is related to the article titled, "Using handwriting to
      infer a writer's country of origin for forensic intelligence purposes" (Agius et
      al., 2017) [1]. This article reports original writer, spatial and construction
      characteristic data for thirty-seven English Australian writers and thirty-seven
      Vietnamese writers. All of these characteristics were coded and recorded in
      Microsoft Excel 2013 (version 15.31). The construction characteristics coded were
      only extracted from seven characters, which were: 'g', 'h', 'th', 'M', '0', '7'
      and '9'. The coded format of the writer, spatial and construction characteristics
      is made available in this Data in Brief in order to allow others to perform
      statistical analyses and modelling to investigate whether there is a relationship
      between the handwriting features and the nationality of the writer, and whether
      the two nationalities can be differentiated. Furthermore, to employ mathematical
      techniques that are capable of characterising the extracted features from each
      participant.

PMID- 29322084
TI  - Data on a delivery of biomolecules into Nicothiana benthamiana leaves using
      different nanoparticles.
AB  - Nanoparticles (NPs) have a number of unique properties associated with their
      ultrasmall size and exhibit many advantages compared with existing plant
      biotechnology platforms for delivery of proteins, RNA and DNA of various sizes
      into the plant cells (Arruda et al., 2015; Silva et al., 2010; Martin-Ortigosa et
      al., 2014; Mitter et al., 2017) [1], [2], [3], [4]. The data presented in this
      article demonstrate a delivery of biomolecules into Nicotiana benthamiana plant
      leaves using various types of NPs including gold, iron oxide and chitosan NPs and
      methods of biolistic bombardment and infiltration. The data demonstrate physical
      characteristics of NPs coated with fluorescently labeled protein and small RNA
      (size and zeta-potential) and visualization of nanocomplexes delivery into cells
      of N. benthamiana leaves by fluorescence microscopy.

PMID- 29322085
TI  - Data on the effect of the dispersion of functionalized nanoparticles TiO2 with
      photocatalytic activity in LDPE.
AB  - This article contains the dataset referring to the article "Study of the effect
      of the dispersion of functionalized nanoparticles TiO2 with photocatalytic
      activity in LDPE" (Jahell et al., 2016) [1]. It includes the FT-IR data of the
      functionalized nanoparticles of TiO2 with Hexadecyltrimethoxysilane in different
      degrees of functionalization, thermogravimetric analysis, distribution and
      particle size in the polymer matrix by scanning electron microscopy (SEM),
      carbonyl index, gravimetry and scanning electron microscopy of the nanocomposite
      degraded by UV radiation.

PMID- 29322087
TI  - The Endosomal Protein Endotubin Is Required for Enterocyte Differentiation.
AB  - Background & Aims: During late embryonic development and through weaning,
      enterocytes of the ileum are highly endocytic. Defects in endocytosis and
      trafficking are implicated in neonatal disease, however, the mechanisms
      regulating trafficking during the developmental period are incompletely
      understood. The apical endosomal protein endotubin (EDTB) is highly expressed in
      the late embryonic and neonatal ileum. In epithelial cells in vitro, EDTB
      regulates both trafficking of tight junction proteins and proliferation through
      modulation of YAP activity. However, EDTB function during the endocytic stage of
      development of the intestine is unknown. Methods: By using Villin-CreERT2, we
      induced knockout of EDTB during late gestation and analyzed the impact on
      endocytic compartments and enterocyte structure in neonates using
      immunofluorescence, immunocytochemistry, and transmission electron microscopy.
      Results: Deletion of the apical endosomal protein EDTB in the small intestine
      during development impairs enterocyte morphogenesis, including loss of the apical
      endocytic complex, defective formation of the lysosomal compartment, and some
      cells had large microvillus-rich inclusions similar to those observed in
      microvillus inclusion disease. There also was a decrease in apical endocytosis
      and mislocalization of proteins involved in apical trafficking. Conclusions: Our
      results show that EDTB-mediated trafficking within the epithelial cells of the
      developing ileum is important for maintenance of endocytic compartments and
      enterocyte integrity during early stages of gut development.

PMID- 29322088
TI  - Successful management of persistent lower extremity lymphedema with suction
      assisted lipectomy.
AB  - Introduction: Lower-extremity lymphedema is a significant complication attributed
      to gynecologic cancer surgery, potentially effectuating severe edema and
      discernible pain. Case report: We report on a patient who developed persistent,
      lower-extremity lymphedema following her treatment for cervix cancer. Despite
      repeated efforts to manage the lymphedema with conventional measures, the
      patient's condition had not markedly improved. Thereafter, she underwent a
      suction-assisted lipectomy that effectively resolved her symptoms. Conclusion:
      Since lymphedema often remains disabling and incurable following traditional
      therapy, suction-assisted lipectomy should be considered as an alternative when
      endeavoring to optimally manage this complication.

PMID- 29322086
TI  - Engineered Livers for Infectious Diseases.
AB  - Engineered liver systems come in a variety of platform models, from 2-dimensional
      cocultures of primary human hepatocytes and stem cell-derived progeny, to 3
      dimensional organoids and humanized mice. Because of the species-specificity of
      many human hepatropic pathogens, these engineered systems have been essential
      tools for biologic discovery and therapeutic agent development in the context of
      liver-dependent infectious diseases. Although improvement of existing models is
      always beneficial, and the addition of a robust immune component is a particular
      need, at present, considerable progress has been made using this combination of
      research platforms. We highlight advances in the study of hepatitis B and C
      viruses and malaria-causing Plasmodium falciparum and Plasmodium vivax parasites,
      and underscore the importance of pairing the most appropriate model system and
      readout modality with the particular experimental question at hand, without
      always requiring a platform that recapitulates human physiology in its entirety.

PMID- 29322090
TI  - New 1,1'-Ferrocene Bis(sulfonyl) Reagents.
AB  - Several new 1,1'-bis(sulfonyl)ferrocenes designed for the synthesis of
      sulfonamide linked biological conjugates have been prepared. 1,1'
      Bis(sulfonylbromide)ferrocene can be produced from the corresponding
      sulfonylchloride via a bis(sulfonylhydrazide) intermediate. Bis(sulfonyl-N
      hydroxybenzotriazole)ferrocene can also be synthesized from the sulfonyl
      chloride, and reaction of glycine methyl ester with the sulfonyl chloride affords
      a [3]ferrocenophane complex. All new compounds have been structurally
      characterized by X-ray crystallography.

PMID- 29322089
TI  - The Wisconsin Registry for Alzheimer's Prevention: A review of findings and
      current directions.
AB  - The Wisconsin Registry for Alzheimer's Prevention is a longitudinal observational
      cohort study enriched with persons with a parental history (PH) of probable
      Alzheimer's disease (AD) dementia. Since late 2001, Wisconsin Registry for
      Alzheimer's Prevention has enrolled 1561 people at a mean baseline age of 54
      years. Participants return for a second visit 4 years after baseline, and
      subsequent visits occur every 2 years. Eighty-one percent (1270) of participants
      remain active in the study at a current mean age of 64 and 9 years of follow-up.
      Serially assessed cognition, self-reported medical and lifestyle histories (e.g.,
      diet, physical and cognitive activity, sleep, and mood), laboratory tests,
      genetics, and linked studies comprising molecular imaging, structural imaging,
      and cerebrospinal fluid data have yielded many important findings. In this
      cohort, PH of probable AD is associated with 46% apolipoprotein E (APOE) epsilon4
      positivity, more than twice the rate of 22% among persons without PH. Subclinical
      or worse cognitive decline relative to internal normative data has been observed
      in 17.6% of the cohort. Twenty-eight percent exhibit amyloid and/or tau
      positivity. Biomarker elevations, but not APOE or PH status, are associated with
      cognitive decline. Salutary health and lifestyle factors are associated with
      better cognition and brain structure and lower AD pathophysiologic burden. Of
      paramount importance is establishing the amyloid and tau AD endophenotypes to
      which cognitive outcomes can be linked. Such data will provide new knowledge on
      the early temporal course of AD pathophysiology and inform the design of
      secondary prevention clinical trials.

PMID- 29322092
TI  - Anderson localizations and photonic band-tail states observed in compositionally
      disordered platform.
AB  - Anderson localization in random structures is an intriguing physical phenomenon,
      for which experimental verifications are far behind theoretical predictions. We
      report the first experimental confirmations of photonic band-tail states and a
      complete transition of Anderson localization. An optically activated photonic
      crystal alloy platform enables the acquisition of extensive experimental data
      exclusively on pure eigenstates, revealing direct evidence of band-tail states
      and Anderson localization transition within the band-tail states. Analyses of
      both experimental and simulated data lead to a comprehensive picture of photon
      localization that is highly consistent with theories by Anderson and others. We
      believe that our results provide a strong experimental foundation upon which both
      the fundamental understandings and application possibility of Anderson
      localization can be promoted significantly.

PMID- 29322091
TI  - A Retroviral Replicating Vector Encoding Cytosine Deaminase and 5-FC Induces
      Immune Memory in Metastatic Colorectal Cancer Models.
AB  - Treatment of tumors with Toca 511, a gamma retroviral replicating vector encoding
      cytosine deaminase, followed by 5-fluorocytosine (5-FC) kills tumors by local
      production of 5-fluorouracil (5-FU). In brain tumor models, this treatment
      induces systemic anti-tumor immune responses and long-term immune-mediated
      survival. Phase 1 Toca 511 and Toca FC (extended-release 5-FC) clinical trials in
      patients with recurrent high-grade glioma show durable complete responses and
      promising survival data compared to historic controls. The work described herein
      served to expand on our earlier findings in two models of metastatic colorectal
      carcinoma (mCRC). Intravenous (i.v.) delivery of Toca 511 resulted in substantial
      tumor-selective uptake of vector into metastatic lesions. Subsequent treatment
      with 5-FC resulted in tumor shrinkage, improved survival, and immune memory
      against future rechallenge with the same CT26 CRC cell line. Similar results were
      seen in a brain metastasis model of mCRC. Of note, 5-FC treatment resulted in a
      significant decrease in myeloid-derived suppressor cells (MDSCs) in mCRC tumors
      in both the liver and brain. These results support the development of Toca 511
      and Toca FC as a novel immunotherapeutic approach for patients with mCRC. A phase
      1 study of i.v. Toca 511 and Toca FC in solid tumors, including mCRC, is
      currently underway (NCT02576665).

PMID- 29322093
TI  - Heralded quantum steering over a high-loss channel.
AB  - Entanglement is the key resource for many long-range quantum information tasks,
      including secure communication and fundamental tests of quantum physics. These
      tasks require robust verification of shared entanglement, but performing it over
      long distances is presently technologically intractable because the loss through
      an optical fiber or free-space channel opens up a detection loophole. We design
      and experimentally demonstrate a scheme that verifies entanglement in the
      presence of at least 14.8 +/- 0.1 dB of added loss, equivalent to approximately
      80 km of telecommunication fiber. Our protocol relies on entanglement swapping to
      herald the presence of a photon after the lossy channel, enabling event-ready
      implementation of quantum steering. This result overcomes the key barrier in
      device-independent communication under realistic high-loss scenarios and in the
      realization of a quantum repeater.

PMID- 29322094
TI  - Electrically switchable metadevices via graphene.
AB  - Metamaterials bring subwavelength resonating structures together to overcome the
      limitations of conventional materials. The realization of active metadevices has
      been an outstanding challenge that requires electrically reconfigurable
      components operating over a broad spectrum with a wide dynamic range. However,
      the existing capability of metamaterials is not sufficient to realize this goal.
      By integrating passive metamaterials with active graphene devices, we demonstrate
      a new class of electrically controlled active metadevices working in microwave
      frequencies. The fabricated active metadevices enable efficient control of both
      amplitude (>50 dB) and phase (>90 degrees ) of electromagnetic waves. In this
      hybrid system, graphene operates as a tunable Drude metal that controls the
      radiation of the passive metamaterials. Furthermore, by integrating individually
      addressable arrays of metadevices, we demonstrate a new class of spatially
      varying digital metasurfaces where the local dielectric constant can be
      reconfigured with applied bias voltages. In addition, we reconfigure resonance
      frequency of split-ring resonators without changing its amplitude by damping one
      of the two coupled metasurfaces via graphene. Our approach is general enough to
      implement various metamaterial systems that could yield new applications ranging
      from electrically switchable cloaking devices to adaptive camouflage systems.

PMID- 29322095
TI  - Low-threshold parametric oscillation in organically modified microcavities.
AB  - Coherent frequency generators are an enabling platform in basic science and
      applied technology. Originally reliant on high-power lasers, recently comb
      generation has been demonstrated in ultrahigh-Q microcavities. The large
      circulating intensity within the cavity results in strong light-matter
      interaction, giving rise to Kerr parametric oscillations for comb generation.
      However, the comb generation threshold is limited by competing nonlinear effects
      within the cavity material and low intrinsic material Kerr coefficients. We
      report a new strategy to fabricate near-infrared frequency combs based on
      combining high-Q microcavities with monomolecular layers of highly nonlinear
      small molecules. The functionalized microcavities demonstrate high-efficiency
      parametric oscillation in the near-IR and generate primary frequency combs with
      0.88-mW thresholds, improving optical parametric oscillation generation over
      nonfunctionalized devices by three orders of magnitude. This organic-inorganic
      approach enables otherwise unattainable performance and will inspire the next
      generation of integrated photonic device platforms.

PMID- 29322096
TI  - Dystrophin gene expression and intracellular calcium changes in the giant
      freshwater prawn, Macrobrachium rosenbergii, in response to white spot symptom
      disease infection.
AB  - Background: Dystrophin, an essential protein functional in the maintenance of
      muscle structural integrity is known to be responsible for muscle deterioration
      during white spot syndrome virus (WSSV) infection among prawn species. Previous
      studies have shown the upregulation of dystrophin protein in Macrobrachium
      rosenbergii (the giant freshwater prawn) upon white spot syndrome virus (WSSV)
      infection. The literature has also suggested the important role of calcium ion
      alterations in causing such muscle diseases. Thus, the interest of this study
      lies within the linkage between dystrophin functioning, intracellular calcium and
      white spot syndrome virus (WSSV) infection condition. Methods: In this study, the
      dystrophin gene from M. rosenbergii (MrDys) was first characterised followed by
      the characterization of dystrophin gene from a closely related shrimp species,
      Penaeus monodon (PmDys). Dystrophin sequences from different phyla were then used
      for evolutionary comparison through BLAST analysis, conserved domain analysis and
      phylogenetic analysis. The changes in mRNA expression levels of dystrophin and
      the alteration of intracellular calcium concentrations in WSSV infected muscle
      cells were then studied. Results: A 1246 base pair long dystrophin sequence was
      identified in the giant freshwater prawn, Macrobrachium rosenbergii (MrDys)
      followed by 1082 base pair long dystrophin sequence in P. monodon (PmDys). Four
      conserved domains were identified from the thirteen dystrophin sequences compared
      which were classified into 5 different phyla. From the phylogenetic analysis,
      aside from PmDys, the characterised MrDys was shown to be most similar to the
      invertebrate phylum of Nematoda. In addition, an initial down-regulation of
      dystrophin gene expression followed by eventual up-regulation, together with an
      increase in intracellular calcium concentration [Ca2+] i were shown upon WSSV
      experimental infection. Discussion: Both the functionality of the dystrophin
      protein and the intracellular calcium concentration were affected by WSSV
      infection which resulted in progressive muscle degeneration. An increased
      understanding of the role of dystrophin-calcium in MrDys and the interactions
      between these two components is necessary to prevent or reduce occurrences of
      muscle degeneration caused by WSSV infection, thereby reducing economic losses in
      the prawn farming industry from such disease.

PMID- 29322097
TI  - Toward a leading indicator of catastrophic shifts in complex systems: Assessing
      changing conditions in nation states.
AB  - The 20th century was characterized by substantial change on a global scale. There
      were multiple wars and unrest, social and political transitions, technological
      innovation and widespread development that impacted every corner of the earth. In
      order to assess the sustainability implications of these changes, we conducted a
      study of three advanced nations particularly affected during this time: France,
      Germany and the United States (USA). All three nation states withstood these
      changes and yet continued to thrive, which speaks to their resilience. However,
      we were interested in determining whether any of these countries underwent a
      regime shift during this period and if they did, whether there was advanced
      warning that transition was imminent. This study seeks to evaluate systemic
      trends in each country by exploring key variables that describe its condition
      over time. We use Fisher Information to assess changing conditions in the nation
      states based on trends in social, economic and environmental variables and employ
      Bayes Theorem as an objective means of determining whether declines in Fisher
      information provide early warning signals of critical transitions. Results
      indicate that while the United States was relatively stable and France
      experienced a great deal of change during this period, only Germany appeared to
      undergo a regime shift. Further, each country exhibited decreasing Fisher
      information when approaching significant events (e.g., World Wars, Great
      Depression), and reflected unique mechanisms linked to dynamic changes in each
      nation state. This study highlights the potential of using trends in Fisher
      information as a sentinel for evaluating dynamic change and assessing resilience
      in coupled human and natural systems.

PMID- 29322098
TI  - Diuron degradation by bacteria from soil of sugarcane crops.
AB  - The isolation of microorganisms from soil impacted by xenobiotic chemicals and
      exposing them in the laboratory to the contaminant can provide important
      information about their response to the contaminants. The purpose of this study
      was to isolate bacteria from soil with historical application of herbicides and
      to evaluate their potential to degrade diuron. The isolation media contained
      either glucose or diuron as carbon source. A total of 400 bacteria were isolated,
      with 68% being Gram-positive and 32% Gram-negative. Most isolates showed
      potential to degrade between 10 and 30% diuron after five days of cultivation;
      however Stenotrophomonas acidophila TD4.7 and Bacillus cereus TD4.31 were able to
      degrade 87% and 68%, respectively. The degradation of diuron resulted in the
      formation of the metabolites DCPMU, DCPU, DCA, 3,4-CAC, 4-CA, 4-CAC and aniline.
      Based on these results it was proposed that Pseudomonas aeruginosa TD2.3,
      Stenotrophomonas acidaminiphila TD4.7, B. cereus TD4.31 and Alcaligenes faecalis
      TG 4.48, act on 3,4-DCA and 4-CA by alkylation and dealkylation while Micrococcus
      luteus and Achromobacter sp follow dehalogenation directly to aniline. Growth on
      aniline as sole carbon source demonstrates the capacity of strains to open the
      aromatic ring. In conclusion, the results show that the role of microorganisms in
      the degradation of xenobiotics in the environment depends on their own metabolism
      and also on their synergistic interactions.

PMID- 29322100
TI  - Bglbrick strategy for the construction of single domain antibody fusions.
AB  - Single domain antibodies, recombinantly expressed variable domains derived from
      camelid heavy chain antibodies, are often expressed as multimers for detection
      and therapeutic applications. Constructs in which several single domain
      antibodies are genetically fused serially, as well as those in which single
      domain antibodies are genetically linked with domains that naturally form
      multimers, yield improvement in apparent binding affinity due to avidity. Here,
      using a single domain antibody that binds envelope protein from the Dengue virus,
      we demonstrated the construction of single domain antibody dimers using the
      Bglbrick cloning strategy. Constructing single domain antibodies and
      multimerization domains as Bglbrick parts enables the easy mixing and matching of
      parts. The dimeric constructs provided enhanced fluorescent signal in assays for
      detection of Dengue virus like particles over the monomeric single domain
      antibody.

PMID- 29322099
TI  - Outbreaks caused by vancomycin-resistant Enterococcus faecium in hematology and
      oncology departments: A systematic review.
AB  - Background: Vancomycin-resistance in Enterococcus faecium (VRE) poses a major
      threat in health care settings. It is well known that patients in hematology and
      oncology departments are especially at risk of nosocomial VRE acquisition. This
      systematic review of the literature provides data on the main sources,
      transmission modes and potential risk factors for VRE acquisition as well as
      appropriate infection control measures in order to terminate such nosocomial
      outbreaks. Methods: Data on nosocomial VRE outbreaks on hematology and oncology
      wards was retrieved from the Outbreak Database and PubMed. Results: A total of 35
      VRE outbreaks describing 757 affected patients and 77 deaths were included in
      this review. The most frequent site of pathogen detection were stool samples or
      rectal swabs (57% of all isolation sites), followed by blood cultures (30%). The
      most common outbreak source was an index patient. The main modes of transmission
      were 1) hands of health care workers, 2) contact to a contaminated environment
      and 3) patient-to-patient contact. The most common risk factor for VRE positivity
      was prior antibiotic treatment. The most common infection control measures
      performed were screening and isolating or cohorting of patients. Conclusion: A
      rational use of antibiotics in hematology and oncology units is recommended in
      order to reduce selection pressure on resistant pathogens such as VRE. In
      addition the importance of hand hygiene should be stressed to all staff whenever
      possible.

PMID- 29322101
TI  - A novel individual-level morphological brain networks constructing method and its
      evaluation in PET and MR images.
AB  - Mapping the human brain is one of the great scientific challenges of the 21st
      century. Brain network analysis is an effective technique based on graph theory
      that is widely used to investigate network patterns in the human brain.
      Currently, mapping an individual brain network using a single image has been a
      hotspot in the field of brain science; techniques, such as the Kullback-Leibler
      (KL) method, have applications in structural Magnetic Resonance (MR) imaging.
      However, maintaining an image's intensity, shape, texture and gradient
      information during feature extraction is very challenging. In this study, we
      propose a novel method for individual-level network construction based on the
      high-resolution Brainnetome Atlas, which shows 246 brain regions. Principal
      components (PCs) were obtained for each brain region using principal component
      analysis (PCA) for feature extraction. Individual brain networks were followed
      and used to construct the PC similarity measurement based on the mutual
      information (MI) method. To evaluate the robustness of the proposed method, three
      independent experiments were carried out. In the first, 34 healthy subjects
      underwent two Carbon 11-labeled Pittsburgh compound B Positron emission
      tomography (11C-PiB PET) scans; in the second, 32 healthy subjects underwent two
      structural MRI scans; and in the last, 10 Alzheimer's disease (AD) subjects and
      10Healthy Control (HC) subjects underwent 11C-PiB PET scans. For each subject,
      network metrics including clustering coefficient, path length, small-world
      coefficient, efficiency and node betweenness centrality were calculated. The
      results suggested that both the individual PET and structural MRI networks
      exhibited a good small-word property, and the variances within subjects was also
      quite small in all metrics, The average value of Coefficient of variation (CV)
      map was 0.33 and 0.32 for PiB PET and MR images respectively, and intra-class
      correlation coefficients (ICC) range from approximately 0.4 to 0.7, indicating
      that the new method was well adapted to the subjects. The results of intra-class
      correlation coefficients from the test-retest experiment were consistent with
      previous research employing KL divergence, but with low computational complexity.
      Further, differences between AD subjects and HC subjects can be observed in
      network metrics. The method proposed herein provides a new perspective for
      investigating individual brain connectivity; it would enable neuroscientists to
      further understand the functions of the human brain.

PMID- 29322102
TI  - Analysis of climate and anthropogenic impacts on runoff in the Lower Pra River
      Basin of Ghana.
AB  - The Lower Pra River Basin (LPRB), located in the forest zone of southern Ghana
      has experienced changes due to variability in precipitation and diverse
      anthropogenic activities. Therefore, to maintain the functions of the ecosystem
      for water resources management, planning and sustainable development, it is
      important to differentiate the impacts of precipitation variability and
      anthropogenic activities on stream flow changes. We investigated the variability
      in runoff and quantified the contributions of precipitation and anthropogenic
      activities on runoff at the LPRB. Analysis of the precipitation-runoff for the
      period 1970-2010 revealed breakpoints in 1986, 2000, 2004 and 2010 in the LPRB.
      The periods influenced by anthropogenic activities were categorized into three
      periods 1987-2000, 2001-2004 and 2005-2010, revealing a decrease in runoff during
      1987-2000 and an increase in runoff during 2001-2004 and 2005-2010. Assessment of
      monthly, seasonal and annual runoff depicted a significant increasing trend in
      the runoff time series during the dry season. Generally, runoff increased at a
      rate of 9.98 * 107m3yr-1, with precipitation variability and human activities
      contributing 17.4% and 82.3% respectively. The dominant small scale alluvial gold
      mining activity significantly contributes to the net runoff variability in LPRB.

PMID- 29322103
TI  - A national survey of MRI safety practices in Ghana.
AB  - Objective: The aim of the present study was to assess current MRI safety
      practices among MRI facilities in Ghana, and their compliance with the 2013
      American College of Radiology (ACR) guidance document on MR safe practices.
      Material and methods: A questionnaire developed from the 2013 ACR Guidance
      Document was used to collect information on magnetic field strengths, MR safety
      policy and compliance, patient screening, emergency preparedness, infection
      control, MRI safety accessories, equipment safety, signage and barriers, report
      of adverse incidents, and access and communication. Results: Out of the 13 MRI
      facilities identified, response rate of 92% was obtained. Six (50%) facilities
      indicated they have MRI safety policy and have it present and readily available
      to facility staff. Five (42%) facilities indicated they have handheld magnets,
      and 1(8%) has ferromagnetic detection system. Only one (8%) had crash carts.
      Seven (58%) facilities have zone 4 clearly marked with a red light and lighted
      sign stating "The Magnet is On". One (8%) recorded projectile incident and fire
      outbreak. Eight (67%) facilities have direct visual observation of access
      corridors to zone IV. Conclusion: There was compliance in some areas of MRI
      safety practice, however there were some shortfalls which need to be addressed.
      We therefore recommend improvement in the following areas: (1) establishment,
      implementation, and maintenance of current MRI safety policy, (2) patient
      screening, (3) provision of training and routine drills on emergency response
      protocols with documentations, (4) emergency preparedness, and (5) provision of
      colour codes for equipment used within MRI environment.

PMID- 29322104
TI  - Soil total carbon and nitrogen and crop yields after eight years of tillage, crop
      rotation, and cultural practice.
AB  - Information on the long-term effect of management practices on soil C and N
      stocks is lacking. An experiment was conducted from 2004 to 2011 in the northern
      Great Plains, USA to examine the effects of tillage, crop rotation, and cultural
      practice on annualized crop residue (stems + leaves) returned to the soil and
      grain yield, and soil total C (STC) and total N (STN) stocks at the 0-120 cm
      depth. Tillage practices were no-tillage (NT) and conventional tillage (CT) and
      crop rotations were continuous spring wheat (Triticum aestivum L.) (CW), spring
      wheat-pea (Pisum sativum L.) (W-P), spring wheat-barley (Hordeum vulgaris L.) hay
      pea (W-B-P), and spring wheat-barley hay-corn (Zea mays L.)-pea (W-B-C-P).
      Cultural practices were traditional (conventional seed rates and plant spacing,
      conventional planting date, broadcast N fertilization, and reduced stubble
      height) and improved (variable seed rates and plant spacing, delayed planting,
      banded N fertilization, and increased stubble height). Crop residue and grain
      yield were greater with CW and W-P than W-B-P and grain yield was greater with
      the traditional than the improved practice. The STC at 10-20 and 90-120 cm was
      greater with CW or W-P than other crop rotations in CT and greater with CW than W
      B-P in NT. The STN at 20-40 cm was greater with W-P than CW and W-B-P in CT. With
      NT and the improved cultural practice, STN at 0-5, 5-10, 20-40, and 60-90 cm was
      greater with W-P and W-B-C-P than other crop rotations. The STN at 0-10 cm
      correlated with annualized crop residue and grain yield (r = 0.94-0.97, P <=
      0.05). Increased crop residue returned to the soil increased soil C stock with CW
      and W-P and N stock with W-P, but removal of aboveground crop biomass for hay
      decreased stocks with W-B-P. Increased soil N stock had a beneficial effect on
      crop grain yield.

PMID- 29322105
TI  - Simple visit behavior unifies complex Zika outbreaks.
AB  - New outbreaks of Zika in the U.S. are imminent. Human nature dictates that many
      individuals will continue to revisit affected 'Ground Zero' patches, whether out
      of choice, work or family reasons - yet this feature is missing from traditional
      epidemiological analyses. Here we show that this missing visit-revisit mechanism
      is by itself capable of explaining quantitatively the 2016 human Zika outbreaks
      in all three Ground Zero patches. Our findings reveal counterintuitive ways in
      which this human flow can be managed to tailor any future outbreak's duration,
      severity and time-to-peak. Effective public health planning can leverage these
      results to impact the evolution of future outbreaks via soft control of the
      overall human flow, as well as to suggest best-practice visitation behavior for
      local residents.

PMID- 29322106
TI  - Questioning the role of Facebook in maintaining Syrian social capital during the
      Syrian crisis.
AB  - The Syrian crisis is considered the 'world's single largest crisis for almost a
      quarter of a century that has the biggest refugee population from a single
      conflict in a generation' (UN High Commissioner for Refugees, 2016). The rapid
      adoption of Facebook among Syrians questions whether it helps in maintaining the
      social capital of a war-torn nation and a dispersed Syrian population worldwide.
      Data was collected by means of a Facebook survey from 964 Syrian users. Results
      indicated that Facebook enhanced social identity and social capital through
      facilitating communication, collaboration and resource sharing among dispersed
      Syrians inside and outside the country. However, the offline rift of the nation
      was extended to Facebook through promoting hate speech among opposed parties.
      Results of this study may advance the understanding of the role of Facebook on
      social capital in countries going through similar crisis situations.

PMID- 29322107
TI  - The effect of light touch on balance control during overground walking in healthy
      young adults.
AB  - Balance control is essential for safe walking. Adding haptic input through light
      touch may improve walking balance; however, evidence is limited. This research
      investigated the effect of added haptic input through light touch in healthy
      young adults during challenging walking conditions. Sixteen individuals walked
      normally, in tandem, and on a compliant, low-lying balance beam with and without
      light touch on a railing. Three-dimensional kinematic data were captured to
      compute stride velocity (m/s), relative time spent in double support (%DS), a
      medial-lateral margin of stability (MOSML) and its variance (MOSMLCV), as well as
      a symmetry index (SI) for the MOSML. Muscle activity was evaluated by integrating
      electromyography signals for the soleus, tibialis anterior, and gluteus medius
      muscles bilaterally. Adding haptic input decreased stride velocity, increased the
      %DS, had no effect on the MOSML magnitude, decreased the MOSMLCV, had no effect
      on the SI, and increased activity of most muscles examined during normal walking.
      During tandem walking, stride velocity and the MOSMLCV decreased, while %DS,
      MOSML magnitude, SI, and muscle activity did not change with light touch. When
      walking on a low-lying, compliant balance beam, light touch had no effect on
      walking velocity, MOSML magnitude, or muscle activity; however, the %DS increased
      and the MOSMLCV and SI decreased when lightly touching a railing while walking on
      the balance beam. The decreases in the MOSMLCV with light touch across all
      walking conditions suggest that adding haptic input through light touch on a
      railing may improve balance control during walking through reduced variability.

PMID- 29322108
TI  - Production of biodiesel by enzymatic transesterification of waste sardine oil and
      evaluation of its engine performance.
AB  - Waste sardine oil, a byproduct of fish industry, was employed as a low cost
      feedstock for biodiesel production. It has relatively high free fatty acid (FFA)
      content (32 mg KOH/g of oil). Lipase enzyme immobilized on activated carbon was
      used as the catalyst for the transesterification reaction. Process variables viz.
      reaction temperature, water content and oil to methanol molar ratio were
      optimized. Optimum methanol to oil molar ratio, water content and temperature
      were found to be 9:1, 10 v/v% and 30  degrees C respectively. Reusability of
      immobilized lipase was studied and it was found after 5 cycles of reuse there was
      about 13% drop in FAME yield. Engine performance of the produced biodiesel was
      studied in a Variable Compression Engine and the results confirm that waste
      sardine oil is a potential alternate and low-cost feedstock for biodiesel
      production.

PMID- 29322109
TI  - Influence of hydrodynamic features in the transport and fate of hazard
      contaminants within touristic ports. Case study: Torre a Mare (Italy).
AB  - The environmental quality of Torre a Mare port (Italy) was assessed evaluating on
      one side, the chemical concentration of nine metals and metalloids within bottom
      sediments and on the other one, by exploring the impact of hydrodynamic
      conditions in contaminant's transport within the most polluted basins. The
      investigated port was selected as case study because it resulted much more
      polluted than it was expected based on the touristic port activities and related
      stressors loading on it. In order to determine the origin and fate of
      contaminants in the port basin, 2D numerical simulations were carried out by
      MIKE21 software. The hydrodynamic module (HD) based on a rectangular grid was
      initially used to characterize the flow field into two domains that cover the
      inner and offshore harbor area. Then, advection-dispersion (AD) and water quality
      (WQ) modules were coupled in order to simulate the simultaneous processes of
      transport and dispersion of hypothetical pollutant sources. The
      dissolved/suspended sediment particulates (DSS) were selected as contaminant
      tracers. The comparative analysis between simulation responses and the real metal
      contaminant distribution showed high agreement, suggesting that contaminants
      mainly come from outside port and tend to accumulate in the inner basin. In fact,
      hydrodynamic circulations cause inflowing streams toward the harbor entrance and
      the particular port morphology hampers the exit of fine sediments from the inner
      basin, enhancing thus the accumulation of sediment-associated contaminants within
      the port area. The study confirms that the quality of touristic port areas
      strongly depends on both pollution sources located within and outside the port
      domain and it is controlled mainly by the hydrodynamic-driven processes.

PMID- 29322110
TI  - Mixotrophic transition induced lipid productivity in Chlorella pyrenoidosa under
      stress conditions for biodiesel production.
AB  - Influence of mixotrophic mode and its transition to various trophic modes under
      stress conditions was assessed during two stage cultivation of Chlorella
      pyrenoidosa. Significant lipid productivity was triggered under low light
      intensity, glucose + bicarbonate supplementation and nitrogen starvation. The
      association between biomass and lipid productivity, fatty acid composition during
      mixotrophic transition was critically evaluated. Biomass in growth phase (GP) and
      stress phase (SP) was 6.14 g/l and 5.14 g/l, respectively, in mixotrophic mode.
      Higher lipid productivity of 284 g/kg and 154.3 g/kg of neutral lipids was
      achieved in SP in mixotrophic-mixotrophic (MM) and mixotrophic-heterotrophic (MH)
      modes, respectively. Stress conditions resulted in high unsaturated fatty acid
      methyl esters in MH mode. In addition, neutral lipid content was 58% in MH and
      52% in MM, that can be attributed to carbon source that is supplemented even in
      stress phase. Exploring such novel strategies can generate sustainable avenues
      for biodiesel production.

PMID- 29322111
TI  - A Patient Advocacy Group Summit, Cancer Care in Turkey and The Society of Breast
      Health.

PMID- 29322112
TI  - Managing Male Mammary Maladies.
AB  - This review examines the symptoms, need for referral and management of the benign
      breast conditions which afflict males, together with the steps that are necessary
      to exclude or confirm male breast cancer. The most common complaint is
      gynaecomastia, either true or pseudo, and the majority of these cases need
      reassurance without over-investigation. Drugs that induce breast enlargement are
      described in order that, when possible, a medication switch can be made. Men
      receiving endocrine therapy for prostate cancer may develop painful gynaecomastia
      and this can be relieved with tamoxifen. All men with breast cancer need
      mammography as part of their work-up but this should not be used as a screening
      technique for symptomatic males. Because of lack of lobular development, both
      cysts and fibroadenomas are very rare in men; but those with nipple discharge
      need referral and investigation as some will have underlying malignancy.

PMID- 29322113
TI  - A Systematic Review and Pooled Analysis of Studies of Oral Etoposide in
      Metastatic Breast Cancer.
AB  - Objective: Oral etoposide has been used as a later line therapy for metastatic
      breast cancer for more than twenty years. Its efficacy and clinical usefulness
      has been suggested in small phase II studies in the metastatic breast cancer
      population and the drug has also the added advantage of convenient oral
      administration. Despite these advantages, the place of oral etoposide in
      treatment of metastatic breast cancer has been challenged in the last decade due
      to introduction of several other chemotherapeutics, including options available
      orally, as well as novel targeted therapies. This report pools the data on
      response rates and survival from all available oral etoposide studies in order to
      reach a more precise estimate of the clinical benefit of the drug. Materials and
      methods: A review of the literature was performed for studies of oral etoposide
      in metastatic breast cancer. Data were extracted from eligible studies and
      summary statistics derived. Calculations of pooled response rates and survival
      estimates were performed according to a random or fixed effect model as
      appropriate. Results: The pooled estimate of Response Rate derived from twelve
      studies found in the English literature was 18.5% (95% CI 11.5-25.5%). The pooled
      estimate of Clinical Benefit Rate (CBR) was 45.8% (95% CI 38.6-53.0%) and median
      Overall Survival (OS) approached 1 year. Summarized adverse effects profile data
      show an overall manageable toxicity. Conclusion: This pooled analysis provides
      evidence of a moderate clinical effectiveness of oral etoposide in metastatic
      breast cancer that could be useful in situations that options are limited but
      active treatment still appropriate.

PMID- 29322114
TI  - Characteristics of Special Type Breast Tumors in Our Center.
AB  - Objective: Breast cancer is a heterogeneous disease with different histological
      types. Ductal breast cancer constitutes the vast majority of the breast cancers.
      However limited data are present in the rest of breast cancers called special or
      rare type breast cancers. Here in this study, we tried to describe the clinical
      features of special type breast cancers in our center. Materials and Methods:
      Retrospective descriptive study was performed in Kocaeli University School of
      Medicine, Department of General Surgery between January 2000 and January 2016.
      Women diagnosed with primary breast cancer other than ductal carcinoma were
      included to the study. In total, 101 patients were evaluated according to
      histologic types, molecular types, Tumor Node Metastasis (TNM) stages, and
      grades. Survival of the patients was also evaluated. Results: Medullary and
      metaplastic types showed basal type; tubular, mucinous, micropapillary carcinoma,
      cribriform, lobular and apocrine tumors showed luminal type molecular pattern.
      Neither the existence of ductal carcinoma nor any histologic types had any
      effects on survival. Apocrine tumors were presented in younger ages. Conclusion:
      Histologic types of breast cancer are closely related with the molecular types of
      the breast cancer. Tumor size, grade, stage of the disease can show differences
      among histological types which might be due to the genetic background, late onset
      or limited number of patients. In order to achieve more significant results,
      multicenter national studies are needed.

PMID- 29322115
TI  - Breast Cancer Screening Behaviors of First Degree Relatives of Women Receiving
      Breast Cancer Treatment and the Affecting Factors.
AB  - Objective: First-degree relatives of women with breast cancer are under higher
      risk when compared with the general population. The aim of this study is to
      evaluate breast cancer screening behaviors of women who are first-degree
      relatives of women with breast cancer and factors affecting these behaviors.
      Materials and Methods: This descriptive study included 240 patient relatives, who
      agreed to participate in the study through contact with first-degree relatives of
      133 patients who were receiving breast cancer treatment at the Oncology and
      Chemotherapy unit of an university hospital in Turkey. Data were collected using
      the "Descriptive Characteristics Form," which consisted of socio-demographic
      characteristics, health history, breast cancer risk level and health beliefs as
      well as the "Breast Cancer Screening Behavior Evaluation Form". Results: Out of
      the subjects, 17% reported doing breast self examination (BSE), 18% reported
      getting clinic breast examination (CBE) and 17% reported getting mammography.
      Logistic regression analysis showed that perceived susceptibility increased BSE
      by 0.57 times and increased mammography by 0.77 times. Physical exercise
      increased CBE by 0.21 times and increased mammography by 0.13 times. Conclusions:
      It was found that women with familial breast cancer history (FBCH) had lower
      participation in screening behaviors. Higher susceptibility perception and
      regular physical exercise are the determinant variables. Women with a higher
      susceptibility can be led towards the screening and their participation can be
      increased. In women with family history, the development of healthy lifestyle
      behaviors like physical exercise should be supported.

PMID- 29322116
TI  - Efficiency of Imaging Modalities in Male Breast Disease: Can Ultrasound Give
      Additional Information for Assessment of Gynecomastia Evolution?
AB  - Objective: The purpose of this study is to present mammography and ultrasound
      findings of male breast lesions and to investigate the ability of diagnostic
      modalities in estimating the evolution of gynecomastia. Materials and Methods:
      Sixty-nine male patients who admitted to Taksim and Bakirkoy Education and
      Research Hospitals and underwent mammography (MG) and ultrasonography (US)
      imaging were retrospectively evaluated. Duration of symptoms and mammographic
      types of gynecomastia according to Appelbaum's classifications were evaluated,
      besides the sonographic findings in mammographic types of gynecomastia. Results:
      The distribution of 69 cases were as follows: gynecomastia 47 (68.11%),
      pseudogynecomastia 6 (8.69%) primary breast carcinoma 7 (10.14%), metastatic
      carcinoma 1 (1.4%), epidermal inclusion cyst 2 (2.8%), abscess 2 (2.8%), lipoma 2
      (2.8%), pyogenic granuloma 1 (1.4%), and granulomatous lobular mastitis 1 (1.4%).
      Gynecomastia patients who had symptoms less than 1 year had nodular gynecomastia
      (34.6%) as opposed to dendritic gynecomastia (61.5%) (p<0.01) based on
      mammography results according to Appelbaum's classifications. In patients having
      symptoms for 1 to 2 years, diffuse gynecomastia (70%) had a higher rate than the
      dendritic type (20%). Patients having the symptoms more than 2 years had diffuse
      gynecomastia (57.1%) while 42.9% had dendritic gynecomastia (p<0.001). With
      sonographic examination patients who had symptoms less than 1 year had higher
      rates of dendritic gynecomastia (92.3%) than noduler type (1.9 %). Patients
      having symptoms for 1 to 2 years had more dentritic gynecomastia (70%) than
      diffuse type (30%). Patients having symptoms more than 2 years had diffuse
      gynecomastia (57.1%) comparable to dendritic gynecomastia (42.9 %). Conclusion:
      Diagnostic imaging modalities are efficient tools for estimation of gynecomastia
      evolution as well as the diagnosis of other male breast diseases. There seems to
      be an incongruity between duration of clinical complaints and diagnostic imaging
      classification of gynecomastia. The use of these high resolution US findings may
      demonstrate an early phase fibrosis especially in patients visualized by
      mammography as with nodular phase.

PMID- 29322117
TI  - Oncoplastic Breast Conserving Surgery: Aesthetic Satisfaction and Oncological
      Outcomes.
AB  - Objective: Oncoplastic breast conserving surgery (BCS) involves radical excision
      of tumors while maintaining the natural breast contours. In this study, we
      present the results of the oncoplastic BCS surgeries performed in our clinic.
      Material and Methods: 13 breast cancer patients who had undergone oncoplastic BCS
      were included in this retrospective study. Postoperative photographs and
      retrospective chart reviews were used to evaluate the results. Aesthetic
      satisfaction level was verbally obtained from the patients. Results: Oncoplastic
      BCS was performed using superomedial, superolateral, superior and inferior
      pedicles. All the patients were highly satisfied with the final aesthetic results
      and tumor free at the postoperative 12 months. Conclusion: Oncoplastic BCS can
      achieve favorable results regarding the final aesthetic appearance and tumor
      control.

PMID- 29322118
TI  - MR Imaging Features of Tubular Carcinoma: Preliminary Experience in Twelve
      Masses.
AB  - Objective: We retrospectively analyzed the magnetic resonance (MR) imaging
      features and diffusion-weighted imaging findings of the 12 masses of 10 patients
      with tubular carcinoma (TC), including mammography and sonography findings.
      Materials and Methods: Mammographic, sonographic and magnetic resonance imaging
      features in 12 histopathologically confirmed masses diagnosed as TC of the breast
      within 10 patients were evaluated. Morphologic characteristics, enhancement
      features, apparent diffusion coefficient (ADC) values were reviewed. Results: On
      mammography (n=5), TC appeared as high density masses with indistinct, spiculated
      or obscured margins. Sonographically, TC appeared as a hypoechoic appearance
      (n=12) with posterior acoustic shadowing in nine. On MR imaging, the margins of
      ten of twelve masses were irregular. Internal enhancement patterns were
      heterogeneous in 10 patients. Dynamic enhancement patterns illustrated plateau
      kinetics (n=8). On the T2-weighted images 4 masses were hypointense, and 8 were
      hyperintense; hypointense internal septation was found in seven of these. Tubular
      carcinoma appeared as hyperintense on diffusion-weighted imaging with ADC values
      of 0.85+/-0.16*10-3 mm2/s that was lower than the normal parenchyma of 1.25+/
      0.25*10-3 mm2/s. Conclusion: According to our study with a limited number of
      cases, tubular carcinomas can be described as hyperintense breast carcinomas with
      or without dark internal septation like appearance on T2-weighted images. Low ADC
      values from DW imaging can be used to differentiate TC from hyperintense benign
      breast lesions.

PMID- 29322119
TI  - Breast Injuries in Female Collegiate Basketball, Soccer, Softball and Volleyball
      Athletes: Prevalence, Type and Impact on Sports Participation.
AB  - Objective: In 2015-2016, over 214,000 female athletes competed at the collegiate
      level in the United States (U.S.). The National Collegiate Athletic Association
      (NCAA) collects injury data; however, breast-related injuries do not have a
      specific reporting category. The exact sequelae of breast injury are unknown;
      however, a relationship between breast injury and fat necrosis, which mimics
      breast carcinoma, is documented outside of sports participation. Breast injuries
      related to motor vehicle collisions, seatbelt trauma, and blunt trauma have been
      reported. For these reasons, it is important to investigate female breast
      injuries in collegiate sports. The objectives of this study are to report the
      prevalence of self-reported breast injuries in female collegiate athletes,
      explore injury types and treatments, and investigate breast injury reporting and
      impact on sports participation. Materials and Methods: A cross-sectional study of
      female collegiate athletes at four U.S. universities participating in basketball,
      soccer, softball, or volleyball. Main outcome measure was a questionnaire
      regarding breast injuries during sports participation. Results: Almost half of
      the 194 participants (47.9%) reported a breast injury during their collegiate
      career, less than 10% reported their injury to health personnel with 2.1%
      receiving treatment. Breast injuries reported by breast injuries reported by
      sport include softball (59.5%), basketball (48.8%), soccer (46.7%), and
      volleyball (34.6%). Conclusions: The long-term effects and sequelae of breast
      injuries reported by female collegiate athletes during sport play are unknown.
      Nearly 50% of participants had a breast injury during sports activities. Although
      18.2% indicated that breast injury affected sports participation, only 9.6% of
      the injuries were reported to medical personnel with 2.1% receiving treatment.

PMID- 29322120
TI  - Juvenile Papillomatosis of the Breast in a Pre-Pubertal Girl: An Uncommon
      Diagnosis.
AB  - Juvenile papillomatosis of the breast represents a rare benign proliferative
      disorder that affects women younger than thirty years of age. Although it is a
      localized lesion, it does not have well-demarcated margins. These patients tend
      to have a strong family history for cancer. As it has similar clinical
      presentation with that of a fibroadenoma, it usually receives the diagnosis of
      the latter in the preoperative period. Nonetheless, it has distinct microscopic
      features such as ductal papillomatosis and cysts that are helpful in the
      diagnosis. In this article, a case of juvenile papillomatosis diagnosed in a
      young girl who presented due to a mass of the breast was presented. For the
      fairly rare case, a total mass excision was performed with preserved breast
      tissue. The exact diagnosis was made by postoperative histopathological
      examination.

PMID- 29322121
TI  - Silicone Granuloma Associated with Pectoral Muscle Involvement after Ruptured
      Breast Implant: a Novel case report.
AB  - In this study, an unusual case of a patient who was previously operated on a
      ruptured breast implant following silicone granuloma associated with pectoral
      muscle involvement is reported. A 72-year-old woman had undergone breast
      augmentation surgery when she was 52-year-old and silicone implant rupture 10
      years later. After 10 years of ruptured silicone implant, her mammography showed
      diffuse, multiple high-density nodules in the left breast. The pectoral muscle
      was significantly hypertrophic. The magnetic resonance imaging showed that the
      pectoral muscle was quite hypertrophic and had heterogeneous enhancement. In
      clinical consideration and the presence of the suspected malignancy, a biopsy was
      performed. The histological analysis identified pectoral muscle and breast
      tissue, which had been mainly replaced by giant cells, along with an apparent
      foreign body response. Silicone granuloma can present itself as a soft tissue
      mass. Malignancy is the most important differential diagnosis. Meticulous follow
      up is recommended for these patients.

PMID- 29322122
TI  - Granulomatous Mastitis Concurrence with Breast Cancer.
AB  - Idiopathic Granulomatous Mastitis (IGM) is a rare, chronic, non-malignant and non
      life-threatening breast disease. IGM may mimic carcinoma of the breast. This case
      report is about concurrence of chronic granulomatous mastitis with breast cancer.
      The important aspect of this case is that it is the 4th case where IGM and breast
      cancer are present concurrently.

PMID- 29322123
TI  - Dehydrogenation of dimethylamine-borane mediated by Group 1 pincer complexes.
AB  - Group 1 salts containing carbazolido NNN pincer ligands are precatalysts for the
      dehydrogenation of Me2NH.BH3. NMR monitoring and DOSY studies show a heavy
      dependence on the metal and solvent, allowing in some cases selective formation
      of dehydrogenation products consistent with hydrogen liberation.

PMID- 29322124
TI  - New approaches to the lithiation kinetics in reaction-limited battery electrodes
      through electrochemical impedance spectroscopy.
AB  - Electrochemical impedance spectroscopy is a widely employed technique probing
      kinetic limitations in the charging of battery electrodes. Hindrance mechanisms
      locate at the interfaces between the active material and the electrolyte, and in
      the bulk of the reacting compound. Rate-limiting mechanisms are viewed as
      resistive circuit elements and can be extracted using standard impedance
      analyzers. Classical impedance models consider charge transport, mainly ion
      diffusion as slower carrier, as the principal kinetic limitation impeding full
      electrode charging. This is indeed the case for many technologically relevant
      battery compounds. In other instances, instead of being diffusion-limited,
      electrodes may undergo charging limitation caused by the kinetics of the
      reduction reaction itself. Specific impedance models for reaction-limited
      mechanisms are summarized here and proved for relevant electrode compounds, in
      particular for conversion or alloying electrodes in which Li+ intake produces a
      full rearrangement of the lattice structure with significant atomic displacement.

PMID- 29322125
TI  - A luminescent Schiff-base heterotrinuclear Zn2Dy single-molecule magnet with an
      axial crystal field.
AB  - We report here the synthesis and investigation into the magnetic properties of a
      luminescent trinuclear Zn2Dy Schiff-base complex that exhibits a zero-field
      single-molecule magnet behaviour. Magneto-structural correlation confirms that
      the axial crystal-field is generated by the phenoxide moieties while the
      characteristic Dy3+-based luminescence is observed.

PMID- 29322126
TI  - Electro-click construction of hybrid nanocapsule films with triggered delivery
      properties.
AB  - Hollow nanocapsules (named Hybridosomes(r)) possessing a polymer/nanoparticle
      shell were used to covalently construct hybrid films in a one-pot fashion. The
      alkyne bearing organic/inorganic Hybridosomes(r) were reticulated with azide
      bearing homobifunctional polyethyleneglycol (PEG) linkers, by using an electro
      click reaction on F-SnO2 (FTO) electrodes. The coatings were obtained by
      promoting the Cu(i)-catalyzed click reaction between alkyne and azide moieties in
      the vicinity of the electrode by the electrochemical generation of Cu(i) ions.
      The physicochemical properties of the covalently reticulated hybrid films
      obtained were studied by SEM, AFM, UV-vis and fluorescence spectroscopy. The one
      pot covalent click reaction between the nanocapsules and the PEG linkers in the
      film did not affect the desirable features of the Hybridosomes(r) i.e. their
      hollow nanostructure their chemical versatility and their pH-sensitivity.
      Consequently, both the composition and the cargo-loading of the Hybridosomes(r)
      films could be tuned, demonstrating the versatility of these hybrid coatings. For
      example, the Hybridosome(r) films were used to encapsulate and release a bodipy
      fluorescent probe in response to either a pH drop or the application of an
      oxidative +1 V potential (vs. Ag/AgCl) at the substrate. By advancing the field
      of electro-synthesized films a step further toward the design of complex
      physicochemical interfaces, these results open perspectives for multifunctional
      coatings where chemical versatility, controllable stability and a hollow
      nanostructure are required.

PMID- 29322127
TI  - Chemical tracer diffusion of Sr and Co in polycrystalline Ca-deficient CaMnO3
      delta with CaMn2O4 precipitates.
AB  - Diffusivity on the A- and B-site of polycrystalline perovskite CaMnO3-delta with
      Ca deficiency and spinel CaMn2O4 (marokite) as a secondary phase was studied
      using chemical tracers and secondary ion mass spectrometry (SIMS) complemented by
      electron probe microanalysis (EPMA). Thin films containing Sr and Co chemical
      tracers were deposited on the polished surface of the polycrystalline composite
      sample followed by annealing at 800-1200  degrees C for 96 h. Diffusion profiles
      for each tracer were determined with SIMS, followed by calculation of diffusion
      coefficients by fitting to appropriate models. The Sr tracer showed mainly
      lattice diffusion, with an activation energy of 210 +/- 30 kJ mol-1, whereas the
      Co tracer showed a combination of lattice and enhanced grain-boundary diffusion,
      with activation energies of 270 +/- 30 kJ mol-1 and 380 +/- 40 kJ mol-1,
      respectively. The diffusivities may be used to predict interdiffusion and
      lifetime of junctions between n-type CaMnO3-delta or CaMnO3-delta/CaMn2O4
      composites and metallization interlayers or p-type leg materials in oxide
      thermoelectrics. In particular, the relatively high effective diffusivity of Co
      in polycrystalline CaMnO3-delta may play a role in the reported fast formation of
      the secondary phase (Ca3Co2-yMnyO6) between p-type Ca3Co3.92O9+delta and n-type
      CaMnO3-delta in a direct p-n thermoelectric junction.

PMID- 29322129
TI  - Bulk and surface properties of the Ruddlesden-Popper oxynitride Sr2TaO3N.
AB  - Oxynitrides with the perovskite structure are promising candidates for
      photocatalysis under visible light due to their appropriate optical and
      electronic properties. Recently, layered perovskites have attracted attention for
      their improved performance with respect to bulk perovskites in photocatalytic
      water splitting. In this paper, we investigate the structural and electronic
      properties of the layered Ruddlesden-Popper oxynitride Sr2TaO3N and its (001) and
      (100) surfaces using density functional theory (DFT) calculations. We find that
      the energetically favoured configuration of the bulk has an in-plane cis anion
      order and exhibits rotations of the TaON octahedra. Furthermore, we show that the
      TaON-terminated (001) surface suppresses exciton recombination due to higher
      energy surface states, giving a potential explanation for the good photocatalytic
      performance.

PMID- 29322130
TI  - Systematic charge distribution changes in Bi- and Pb-3d transition metal
      perovskites.
AB  - Charge distribution changes in Bi- and Pb-3d transition metal perovskite type
      oxides were examined by comprehensive precise structural analysis, spectroscopy,
      and theoretical investigations. The change in the depth of the d level of the
      transition metal caused the intermetallic charge transfer. A temperature-induced
      charge-transfer transition in chemically modified BiNiO3 results in
      technologically important negative thermal expansion.

PMID- 29322131
TI  - Steric control in the metal-ligand electron transfer of iminopyridine-ytterbocene
      complexes.
AB  - A systematic study of reactions between Cp*2Yb(THF) (Cp* = eta5-C5Me5, 1) and
      iminopyridine ligands (IPy = 2,6-iPr2C6H3N[double bond, length as m-dash]CH(C5H3N
      R), R = H (2a), 6-C4H3O (2b), 6-C4H3S (2c), 6-C6H5 (2d)) featuring similar
      electron accepting properties but variable denticity and steric demand, has
      provided a new example of steric control on the redox chemistry of ytterbocenes.
      The reaction of the unsubstituted IPy 2a with 1, either in THF or toluene, gives
      rise to the paramagnetic species Cp*2YbIII(IPy)- (3a) as a result of a formal one
      electron oxidation of the YbII ion along with IPy reduction to a radical-anionic
      state. The reactions of 1 with substituted iminopyridines 2b-d, bearing aryl or
      hetero-aryl dangling arms on the 6 position of the pyridine ring occur in a non
      coordinating solvent (toluene) only and afford coordination compounds of a
      formally divalent ytterbium ion, coordinated by neutral IPy ligands
      Cp*2YbII(IPy)0 (3b-d). The X-ray diffraction studies revealed that 2a-c act as
      bidentate ligands; while the radical-anionic IPy in 3a chelates the YbIII ion
      with both nitrogens, neutral IPy ligands in 3b and 3c participate in the metal
      coordination sphere through the pyridine nitrogen and O or S atoms from the furan
      or thiophene moieties, respectively. Finally, in complex 3d the neutral IPy
      ligand formally adopts a monodentate coordination mode. However, an agostic
      interaction between the YbII ion and an ortho C-H bond of the phenyl ring has
      been detected. Imino-nitrogens in 3b-d are not involved in the metal
      coordination. Variable temperature magnetic measurements on 3a are consistent
      with a multiconfigurational ground state of the Yb ion and suggest that the
      largest contribution arises from the 4f13-radical configuration. For complexes 3b
      and 3c the data of magnetic measurements are indicative of a YbII-closed shell
      ligand electronic distribution. Complex 3d is characterized by a complex magnetic
      behavior which does not allow for an unambiguous estimation of its electronic
      structure. The results are rationalized using DFT and CSSCF calculations. Unlike
      diazabutadiene analogues, 3a does not undergo a solvent mediated metal-ligand
      electron transfer and remains paramagnetic in THF solution. On the other hand,
      complexes 3b-d readily react with THF to afford 1 and free IPy 2b-d.

PMID- 29322132
TI  - Facile three-step synthesis and photophysical properties of [8]-, [9]-, and
      [12]cyclo-1,4-naphthalene nanorings via platinum-mediated reductive elimination.
AB  - Herein we report a facile three-step synthesis of [8]-, [9]-, and [12]cyclo-1,4
      naphthalene nanorings as the conjugated segments of carbon nanotubes. The
      nanorings were created via a platinum-mediated assembly of 1,4-naphthalene-based
      units and subsequent reductive elimination in the presence of triphenylphosphine.
      This present platinum-mediated approach is attractive because of its simple three
      step process to produce the targeted nanorings in a high overall yield. In
      addition, their photophysical properties were studied using UV-vis spectroscopy
      and photoluminescence (PL) spectroscopy, which further revealed their unique size
      dependent properties.

PMID- 29322133
TI  - Anti-fibrotic activity of polyphenol-enriched sugarcane extract in rats via
      inhibition of p38 and JNK phosphorylation.
AB  - Sugarcane (Saccharum officinarum L.), which is one of the most important sources
      of sugar, is also rich in polyphenolic compounds. In this study, polyphenols from
      sugarcane were extracted, and the dominant component was characterized
      quantitatively via HPLC to be (-)-epicatechin. Fibrosis occurs in many organs and
      is associated with severe tissue damage. Liver fibrosis is the excessive
      accumulation of extracellular matrix proteins and advanced liver fibrosis,
      resulting in cirrhosis, liver failure and portal hypertension. Thus, the
      prevention and treatment of liver fibrosis is urgent. Therefore, we further
      investigated the protective effect of sugarcane polyphenol extract (SPE) on
      carbon tetrachloride-induced liver fibrosis in rats and observed that SPE (20 or
      50 mg kg-1) improved the serum GOT (glutamic oxaloacetic transferase) and GPT
      (glutamic pyruvate transaminase) levels and decreased the expression of alpha
      smooth muscle actin (alpha-SMA) in liver tissues. The mechanistic study showed
      that in transforming growth factor beta1(TGF-beta1)-induced hepatic stellate
      cells (HSCs), SPE attenuated the phosphorylation of p38 and JNK1/2 and down
      regulated the expression of alpha-SMA. Collectively, SPE mitigated carbon
      tetrachloride-induced liver fibrosis in rats and its mechanism may be related to
      the p38 and JNK signalling pathways.

PMID- 29322134
TI  - Label-free detection of fibrinogen based on the fibrinogen-enhanced peroxidase
      activity of a fibrinogen-hemin composite.
AB  - A simple, label-free colorimetric method for the determination of fibrinogen
      (Fib) in plasma is presented. In this work, it was observed that Fib interacted
      with hemin to form a hemin-Fib composite. Because Fib prevented hemin from the
      formation of m-oxo-dimers, the hemin-Fib composite possesses excellent peroxidase
      like activity. Importantly, the peroxidase-like activity of Fib-hemin increased
      with the increase in the Fib. This allows us to utilize the H2O2-ABTS
      colorimetric system for the quantitative analysis of Fib. This optimized method
      provided a linear determination range of 2.0-100 pM with a correlation of 0.9975.
      The limit of detection for Fib was experimentally determined to be 0.7 pM based
      on a signal-to-noise ratio (S/N) of 3. This novel approach provides a rapid,
      sensitive, cost efficient and robust bioassay for detection of Fib in pathology
      and clinical applications.

PMID- 29322135
TI  - Quinoline-para-quinones and metals: coordination-assisted formation of quinoline
      ortho-quinones.
AB  - The reaction of the para-quinone 6,7-dichloroquinoline-5,8-dione with various
      transition metal dimers led to the unexpected formation of quinoline-ortho
      quinone metal complexes. Systematic variation of the reaction conditions helped
      identify the solvent as the source of the carbonyl oxygen.

PMID- 29322137
TI  - Extremely low loading of Ru species on hydroxyapatite as an effective
      heterogeneous catalyst for olefin epoxidation.
AB  - We report a new class promising heterogeneous catalyst for olefin epoxidation
      based on 0.05 wt% Ru species supported on hydroxyapatite, which was prepared
      through a simple cation-exchange process between RuCl3.nH2O and hydroxyapatite.
      The new catalyst showed high activity, excellent selectivity and good
      recyclability for various olefins in the presence of molecular oxygen and iso
      butyraldehyde as co-oxidants.

PMID- 29322138
TI  - Separation and characterization of cellulose nanocrystals by multi-detector
      asymmetrical-flow field-flow fractionation.
AB  - Cellulose nanocrystals (CNCs) are renewable, naturally derived polymeric
      nanomaterials receiving substantial attention for a wide range of potential
      applications. The recent availability of high quality reference materials will
      facilitate the development and validation of measurement methods needed to
      advance the scientific and commercial use of CNCs. In the present study, we
      demonstrate an optimized method to fractionate CNCs with narrow size dispersion
      based on asymmetrical-flow field-flow fractionation (AF4) coupled with on-line
      multi-angle light scattering (MALS), dynamic light scattering (DLS), and
      differential refractometry (dRI). A stable suspension of CNC (Certified Reference
      Material CNCD-1, National Research Council-Canada) in deionized water was
      prepared using a dispersion method provided by NRC and adopted from a protocol
      originally developed at the National Institute of Standards and Technology. The
      as-prepared material was initially characterized in batch mode to validate the
      NRC dispersion method. AF4 was then optimized for channel and cross flow, mobile
      phase composition, and injection volume, among other parameters. Additionally,
      suspensions containing (1.25-10) mg mL-1 CNC were injected directly into the dRI
      detector (off-line), yielding a dn/dc value of 0.148 +/- 0.003 mL g-1. dRI was
      then used as an on-line mass sensitive detector to quantify recovery. Results
      show that maximum recovery (~ 99%) was achieved under optimized conditions. The
      weight-averaged molar mass (Mw) was estimated at roughly 107 Da from a partial
      Zimm analysis. The optical radius of gyration, Rg, and the hydrodynamic radius,
      Rh, were measured during elution. The shape factor (Rg/Rh) ranged from 1.5 to 1.9
      for the fractionated material, supporting an elongated or rod-like structure. To
      our knowledge, this is the first time that both the morphology and molar mass of
      CNCs have been directly measured for the full distribution of species. Finally,
      we developed and demonstrated a semi-preparatory fractionation method to separate
      CNCs at the milligram scale for off-line research and analysis.

PMID- 29322139
TI  - Effects of polysaccharides from purple sweet potatoes on immune response and gut
      microbiota composition in normal and cyclophosphamide treated mice.
AB  - In this study, three polysaccharides including water-soluble polysaccharide
      (WSP), dilute alkali-soluble polysaccharide (DASP) and concentrated alkali
      soluble polysaccharide (CASP) were extracted from purple sweet potatoes and then
      administered to normal and cyclophosphamide (CTX) treated mice by gavage. The
      results showed that WSP and CASP could restore the spleen index and immune
      cytokine (IL-2 and IL-6) levels in CTX treated mice, while DASP could enhance the
      levels of TNF-alpha, IL-2 and IL-6. As compared to the normal control group, WSP
      and CASP treatment groups exhibited increased levels of Bacteroidetes,
      Lachnospiraceae and Oscillospira, but decreased levels of Firmicutes,
      Alcaligenaceae and Sutterella in normal mice. When compared with a model control
      group, all the three polysaccharide treatment groups showed relatively higher
      abundances of Bacteroidetes, Ruminococcaceae, Lachnospiraceae, Ruminococcus and
      Oscillospira but lower levels of Firmicutes, Proteobacteria, Alcaligenaceae and
      Sutterella in CTX treated mice. Moreover, all the polysaccharides could enhance
      the production of acetic acid, propionic acid and butyric acid in normal mice,
      while WSP could upregulate the production of these short chain fatty acids in CTX
      treated mice.

PMID- 29322140
TI  - Development of antioxidant gliadin particle stabilized Pickering high internal
      phase emulsions (HIPEs) as oral delivery systems and the in vitro digestion fate.
AB  - In this paper, we demonstrate for the first time the use of gliadin particles to
      structure algal oil (rich in DHA) and to exert chemical stability against lipid
      oxidation via the Pickering high internal phase emulsion (HIPE) strategy. The
      gliadin/chitosan colloid particles (GCCPs) were effectively adsorbed and anchored
      at the algal oil-water interface. Concomitantly, the particle-coated droplets as
      building blocks constructed a percolating 3D-network framework, endowing
      Pickering HIPEs with viscoelastic and self-supporting attributes. In addition,
      Pickering HIPEs loaded with shell (HIP-curEs) or core curcumin (HIPEs-cur) were
      constructed to depress the oxidation of algal oil. The content of primary (lipid
      hydroperoxides) and secondary (malondialdehyde and hexanal) oxidation products in
      HIPEs was lower than that in bulk oil. The oxidative stability of HIPEs was
      further improved in shell and core curcumin. An in vitro gastrointestinal (GI)
      model was constructed to characterize the lipid digestion, lipid oxidation as
      well as curcumin bioaccessibility of the ingested Pickering HIPEs. Lipid
      oxidation in the Pickering HIPEs was retarded under GI fluids, especially in the
      presence of core curcumin. The free fatty acid (FFA) fraction released was below
      30% for all HIPEs, reflecting that the Pickering HIPEs formed restrict the
      digestion of fat or oil and potentially help to fight obesity. Interestingly,
      this route enhanced the bioaccessibility of curcumin from only 2.13% (bulk algal
      oil) to 53.61% (core curcumin); in particular, it reached 76.82% for shell
      curcumin. These results help to fill the gap between the physicochemical
      performance of the gliadin particle stabilized Pickering HIPEs and their
      potential applications as oral delivery systems of nutraceuticals. This work
      opens concomitantly an attractive strategy to convert liquid oils into
      antioxidant soft solids without artificial trans fats, as a potential alternative
      for PHOs.

PMID- 29322141
TI  - Polydiacetylenic nanofibers as new siRNA vehicles for in vitro and in vivo
      delivery.
AB  - Polydiacetylenic nanofibers (PDA-Nfs) obtained by photopolymerization of
      surfactant 1 were optimized for intracellular delivery of small interfering RNAs
      (siRNAs). PDA-Nfs/siRNA complexes efficiently silenced the oncogene Lim-1 in the
      renal cancer cells 786-O in vitro. Intraperitoneal injection of PDA-Nfs/siLim1
      downregulated Lim-1 in subcutaneous tumor xenografts obtained with 786-O cells in
      nude mice. Thus, PDA-Nfs represent an innovative system for in vivo delivery of
      siRNAs.

PMID- 29322142
TI  - Nanoconfinement effects of chemically reduced graphene oxide nanoribbons on
      poly(vinyl chloride).
AB  - Polymeric nanocomposites with graphene-based nanocarbons (GNCs) have been
      extensively studied with emphasis on the percolation of nanofillers toward
      electrical, rheological, and mechanical reinforcement. In this study, we report
      an unusual indirect reinforcing phenomenon of highly defective GNCs dispersed in
      the poly(vinyl chloride) (PVC) matrix via densification of the polymer packing
      originating from nanoscale confinement. Herein, chemically reduced graphene oxide
      nanoribbons (C-rGONRs) are employed as a nanofiller. The inclusion of defective
      and oxygen-functionalized C-rGONRs resulted in a dramatic densification of the
      PVC host with extremely low C-rGONR loading, largely exceeding the theoretical
      calculation from a rule of mixture. Along with the densification, the glass
      transition temperature of PVC also increased by 28.6  degrees C at 0.1 wt% filler
      loading. Remarkably, the oxygen barrier property and mechanical toughness under
      tension for the PVC/C-rGONR nanocomposite were the maximum when the greatest
      densification occurred. The structure-property relationship of the nanocomposites
      has been discussed with an emphasis on the nanoscale confinement phenomenon.

PMID- 29322143
TI  - Oxidative dehydrogenation reaction of short alkanes on nanostructured carbon
      catalysts: a computational account.
AB  - Recent progress from first principles computational studies is presented for
      catalytic properties of nanostructured carbon catalysts in the oxidative
      dehydrogenation (ODH) reaction of short alkanes. Firstly, a brief introduction is
      given on the development of carbon catalysts in ODH since 1970. Oxygen functional
      groups have pivotal importance for ODH on nanostructured carbon catalysts. We
      discuss the oxidation process by HNO3 on pristine and defective carbon materials.
      The interactions between the oxygen molecule (oxidant) and the nanostructured
      carbon catalysts are quantitatively calibrated. Moreover the different
      nucleophilic abilities of oxygen functional groups are carefully compared and the
      strongest nucleophilic sites are proposed. The active sites and detailed reaction
      pathway are revealed from several computational studies. Diketone/quinone groups
      are generally considered to be the active centers in ODH. A reaction pathway via
      radical formation is considered as the favorable path. Furthermore, single ketone
      and carbon sites are verified to be active in ODH from the analysis of
      aromaticity. Heteroatom doping effects in ODH are examined. Nitrogen doping is
      found to be very reactive towards oxygen molecule activation. Other dopants such
      as boron, phosphorous and sulfur also have positive effects on the reactivity of
      ODH. Extensive calculations suggest that the BEP relation is applicable for the
      doped nanostructured carbon catalysts. In the end, an outlook for the future
      direction of the computational study is supplied.

PMID- 29322144
TI  - Structure, gelation, and antioxidant properties of curcumin-doped casein micelle
      powder produced by spray-drying.
AB  - The encapsulation of curcumin in micellar caseins (MCs) and the production of
      powder were performed by spray-drying. Nearly 97% of the curcumin was retained
      and the yellow powder showed a typical high casein powder morphology. The
      hygroscopic properties were determined, slight differences reflected less
      available hydrophobic sites when curcumin was bound to casein, favoring
      interactions with water in curcumin-enriched MC powders. No difference was
      detected on the internal MC structure via SAXS. The antioxidant activity of doped
      curcumin powder presented 88% of active curcumin. For 60 days at 40  degrees C
      storage, the antioxidant activity of curcumin measured by ABTS and FRAP assays
      was preserved with a percentage of 82 +/- 2.0% and 84 +/- 1.1%, respectively.
      Curcumin doped powders presented similar features to classical casein powders
      (rehydration and gelling abilities). It was demonstrated that curcumin
      encapsulation in MCs in its powder form helped in protecting its antioxidant
      activity without influencing the techno-functional properties of MCs. This study
      allowed the incorporation of curcumin via the MC matrix as an active food
      ingredient available in a powder state usable as classical milk powder in several
      food formulations.

PMID- 29322146
TI  - KL double core hole pre-edge states of HCl.
AB  - The formation of double core hole pre-edge states of the form 1s-12p
      1(1,3P)sigma*,nl for HCl, located on the binding energy scale as deep as 3 keV,
      has been investigated by means of a high resolution single channel electron
      spectroscopy technique recently developed for the hard X-ray region. A detailed
      spectroscopic assignment is performed based on ab initio quantum chemical
      calculations and by using a sophisticated fit model comprising regular Rydberg
      series. Quantum defects for the different Rydberg series are extracted and the
      energies for the associated double core hole ionization continua are
      extrapolated. Dynamical information such as the lifetime width of these double
      core-hole pre-edge states and the slope of the related dissociative potential
      energy curves are also obtained. In addition, 1s-12p-1V-1nllambdan'l'lambda'
      double shake-up transitions and double core hole states of the form 1s-12s
      1(1,3S)sigma*,4s are observed.

PMID- 29322147
TI  - Self-assembly of 1,3,5-benzenetribenzoic acid on Ag and Cu at the liquid/solid
      interface.
AB  - Assembly of 1,3,5-benzenetribenzoic acid (H3BTB) from solution on Au substrates
      modified by underpotential deposited Ag and Cu layers was studied by near edge X
      ray absorption fine structure spectroscopy, X-ray photoelectron spectroscopy and
      scanning tunneling microscopy. Adsorption of H3BTB on Cu resulted in disordered
      layers with sporadic occurrence of ordered molecular aggregates. In contrast,
      highly ordered layers were obtained on Ag which exhibit a pronounced row
      structure and involve a monopodal bidentate adsorption geometry of the molecules
      through carboxylate coordinating bonding. The row structure arises from pi
      stacking of the molecules and is accompanied by hydrogen bonding interactions
      between the COOH groups of adjacent rows. As a consequence of the geometry of the
      H3BTB molecule and the dominance of intermolecular over molecule-substrate
      interactions, the SAM forms an open structure featuring a grooved surface and
      nanotunnels.

PMID- 29322149
TI  - Exploring physical and chemical properties in new multifunctional indium-,
      bismuth-, and zinc-based 1D and 2D coordination polymers.
AB  - Main group element coordination polymers (MGE-CPs) are important compounds for
      the development of multifunctional materials. However, there has been a shortage
      of studies regarding their structural, optical, catalytic, mechanical, and
      antibacterial properties. This work presents an exhaustive study of a set of
      crystalline MGE-CPs obtained from bismuth and indium metals and iminodiacetate,
      1,2,4,5-benzenetetracarboxylate, and 2,2'-bipyridine as building blocks. An in
      depth topological analysis of the networks was carried out. Additionally,
      nanoindentation studies were performed on two representative low-dimensional
      compounds in order to find the relationships between their structural features
      and their intrinsic mechanical properties (hardness and elasticity). The solid
      state photoluminescence (SSPL) properties were also studied in terms of
      excitation, emission, lifetimes values, and CIE chromaticites. Moreover, the
      heterogeneous catalytic activities of the compounds were evaluated with the
      cyanosilylation reaction using a set of carbonylic substrates under solvent-free
      conditions. Finally, the inhibitory effect of the Bi-CPs on the growth of
      microorganisms such as Escherichia coli, Salmonella enterica serovar Typhimurium,
      and Pseudomonas aeruginosa, which are associated with relevant infectious
      diseases, is reported.

PMID- 29322150
TI  - Water oxidation by simple manganese salts in the presence of cerium(iv) ammonium
      nitrate: towards a complete picture.
AB  - For the first time, using scanning electron microscopy, transmission electron
      microscopy, X-ray absorption near edge structure and extended X-ray absorption
      fine structure X-ray diffraction, it is showed that MnCO3, MnWO4, Mn3(PO4)2.3H2O,
      MnS and Mn(VO3)2.xH2O under the water-oxidation conditions and in the presence of
      cerium(iv) ammonium nitrate, are converted to Mn oxide without a high-range
      order. A mechanism is proposed for such conversion and as Mn oxide is an
      efficient water-oxidizing catalyst, it is thus a candidate as a contributor to
      the observed catalytic activity.

PMID- 29322151
TI  - Hidden aryl-exchange processes in stable 16e RhIII [RhCp*Ar2] complexes, and
      their unexpected transmetalation mechanism.
AB  - Experiments mixing the stable 16e 5-coordinate complexes [RhCp*Ar2] (Cp* = C5Me5;
      Ar = C6F5, C6F3Cl2-3,5) uncover fast aryl transmetalations. Unexpectedly, as
      supported computationally, these exchanges are not spontaneous, but catalyzed by
      minute amounts of 18e (MU-OH)2[RhCp*Ar]2 as a source of 16e [RhCp*Ar(OH)]. The OH
      group is an amazingly efficient bridging partner to diminish the activation
      barrier of transmetalation.

PMID- 29322152
TI  - Computational exploration of Fe55@C240-catalyzed Fischer-Tropsch synthesis.
AB  - Single-shell carbon-encapsulated iron nanoparticles (SCEINs), Fe@C, have been
      shown to be charge-transfer complexes that can act as effective catalysts in the
      hydrogen and oxygen evolution reactions. A new generation of Fe-based catalysts
      for Fischer-Tropsch synthesis (FTS) which resembles SCEINs, e.g. single carbide
      nanoparticles encapsulated in carbon shells, has demonstrated enhanced activity
      and stability for FTS as compared to other carbon-supported Fe-based FTS. Thus
      the catalytic ability of SCEINs for the water splitting reactions and the Fe
      based FTS catalyst with SCEINs-like features stimulated our exploration of SCEINs
      catalyzed FTS. We performed ab initio DFT calculations using a realistic SCEINs
      model system Fe55@C240 to investigate for the first time the adsorption of the
      main reactants in FTS (CO and H/H2) and further to evaluate the catalytic ability
      of Fe55@C240 by reproducing the key steps of the well-known Fe-based FTS
      mechanisms (carbide, enol and CO insertion). Our calculations revealed: (i) a
      determinant role of Fe in enhancing CO adsorption (ii) strong cooperative effects
      with the adsorbates that stabilize the binding (iii) a less favourable two-sites
      reaction on Fe55@C240 due to preferential positions of the reactants farther to
      each other which prevent enol and carbide FTS mechanisms. We propose therefore a
      possible CO insertion path for hydrocarbon growth on Fe55@C240.

PMID- 29322154
TI  - Polyelectrolyte multilayers under compression: concurrent osmotic stress and
      colloidal probe atomic force microscopy.
AB  - Colloidal interactions have been characterised using both osmotic stress and
      surface forces. Here these methods are employed concurrently to measure the
      interaction forces of polyelectrolyte multilayers that when cross-linked form a
      dextran impermeable membrane. The force data, corrected for the thickness of the
      polyelectrolyte multilayer film, has been expressed as pressure versus separation
      enabling the interaction from osmotic stress measurements to be compared to the
      measured interaction from the colloid probe technique. The combined technique is
      valuable in evaluating the interaction forces associated with compression of
      polymer films at different rates and over a wide range of pressure and
      demonstrates features that are not revealed when just one technique is employed.
      The combination of the techniques allows both attractive forces and strongly
      repulsive forces to be measured and shows that the measured repulsion is greater
      in the force data than in the osmotic data. This is due to insufficient
      equilibration time in the AFM measurements, even at the slowest approach rates
      available, indicating that AFM force measurements between polyelectrolytes will
      always contain a dynamic component. That is we demonstrate that colloid probe
      measurements between polymer surfaces overestimate the equilibrium repulsive
      interaction due to the rate at which the measurement is performed.

PMID- 29322155
TI  - Can the Stockholm convention address the spectrum of chemicals currently under
      regulatory scrutiny? Advocating a more prominent role for modeling in POP
      screening assessment.
AB  - Frameworks for chemical regulation are based on the science at the time they were
      written. Today some regulations are being applied to a much broader spectrum of
      chemicals than we had knowledge of when the regulations were written. This
      entails a risk that the regulations are being used outside of their chemical
      application domain. This question is explored using the POP screening assessment
      in the Stockholm convention, which was developed 20 years ago. Using
      perfluorinated alkyl acids (PFAAs) as an example, it is shown that the assessment
      can lead to false negative conclusions. A second case study using
      octamethylcyclotetrasiloxane (D4) illustrates that there is also a risk of false
      positives. The risk for false negative classification of PFAAs is due to the
      inclusion of a screening criterion - bioaccumulation - that is not a requirement
      for adverse effects of chemicals in remote regions. For D4 the risk of false
      positive classification stems from the four screening criteria (persistence,
      bioaccumulation, long-range transport, and adverse effects) applying to different
      environmental media/compartments. The major lesson is that applying the POP
      screening procedure to the broad spectrum of chemicals in modern commerce will
      require that we rely less on the individual screening criteria and more on the
      comparison of estimated exposure and the thresholds for effects stipulated in
      Annex D, paragraph 2 of the convention. Models have an important role to play in
      this context and should become more strongly integrated into the POP screening
      process.

PMID- 29322156
TI  - Effect of lattice strain on the electro-catalytic activity of IrO2 for water
      splitting.
AB  - The lattice strain of IrO2 plays a critical role in determining its OER activity.
      The Ir-O bond length change in IrO6 coordination induces lattice strain.
      Increasing the annealing temperature results in a stretching strain along the c
      axis and a compressive strain on the a and b axes, leading to a larger c/a ratio.
      Enhancing the lattice strain decreases the c/a ratio, which is beneficial for
      improving OER activity.

PMID- 29322157
TI  - Two-way vapochromism of a luminescent platinum(ii) complex with phosphonic-acid
      functionalized bipyridine ligand.
AB  - A luminescent Pt(ii) complex [Pt(CN)2(H4dpbpy)] (1P; H4dpbpy = 2,2'-bipyridine
      4,4'-diphosphonic acid) bearing a phosphonic-acid-functionalized bipyridine
      ligand was successfully synthesized and its unique two-way vapochromic behaviour
      investigated. X-ray structure analyses of both the anhydrous 1P and penta
      hydrated 1P.5H2O phases clearly reveal the activation of intermolecular PtPt
      interactions through the adsorption of water vapour. Emission spectroscopy
      reveals that the penta-hydrated 1P.5H2O complex exhibits an orange emission at
      585 nm that shifts in two directions, to a blue-green emission at 469 nm by
      drying at 100  degrees C or to a red emission at 701 nm by drying under vacuum at
      room temperature. Thermogravimetric analyses and powder X-ray diffraction studies
      clearly reveal that anhydrous 1P, with negligible intermolecular PtPt
      interactions, is formed by drying at 100  degrees C whereas the monohydrate
      1P.H2O phase, with effective PtPt interactions, is formed by drying under vacuum.

PMID- 29322158
TI  - Archaeological evidence for Pott's disease on historical populations: Tomb 05 at
      the Roman Circus maqbara as an example of social solidarity (Toledo, Spain).
AB  - ABSTRACT: World societies can often be characterized by their attitude towards
      elderly and illness. It is well known that most cultures were concerned about
      those who were not able to produce and take care of themselves. This brings to
      the development of social processes that involve such individuals within the
      community, resulting in groups who stick together, and at last, ensuring the
      survival of the group. The contextualization of many of those social processes
      might be studied through Physical Anthropology and Paleopathology. This paper
      presents tomb 05 (T-05) as a new case of probable tuberculosis in Toledo from the
      medieval maqbara of the Roman Circus that provides new paleoanthropological data
      to understand the treatment given to sick people in a sparsely studied context.

PMID- 29322159
TI  - Interpersonal violence among the Chalcolithic and Bronze Ages inhabitants living
      on the Central Plateau of Iran: A voice from Tepe Hissar.
AB  - ABSTRACT: The site of Tepe Hissar (Iran) experienced widespread cultural and
      economic changes during the Chalcolithic and Bronze Ages (5th to the 2nd
      millennium B.C.). The discovery of evidence of burning, including charred human
      remains, the destruction of buildings (Periods II and III), and the presence of
      several mass-burials with comingling of human skeletal remains consisting of ten
      or more individuals (Period III), suggests interpersonal violence during these
      periods. The original excavator of Tepe Hissar, Erich Schmidt, suggested that
      phenomena such as war, massacres, epidemics, or similar catastrophes, may have
      been responsible for the excavated archaeological evidence. This study tests the
      hypothesis that interpersonal violence was responsible for this evidence.
      Patterns of violence related head injury are explored among 129 adult men and
      women from the Chalcolithic and Bronze Ages. Sixty of the 129 (46.5%) crania
      examined presented with cranial trauma, with 25 (19.3%) having evidence of
      perimortem injury, and four (3.1%) and 31 (24%) individuals with signs of healing
      and healed head/facial trauma, respectively. Most of the injuries were located on
      the frontal or parietal bones of the cranium. Such findings may be interpreted as
      a result of the population experiencing a rise in social complexity and
      population increase that accompanied violence related to intra- or inter-group
      competition, often leading to lethal outcomes. These data support the hypothesis
      that the cultural and economic transitions and population changes that occurred
      at Tepe Hissar, and particularly in the Hissar II and III periods, were
      accompanied by tension and interpersonal violence.

PMID- 29322160
TI  - Underweight, overweight and obesity in children and adolescents from Minsk,
      Belarus in the period 2001-2008.
AB  - ABSTRACT: Objective: The aim of the study is to consider the prevalence of all
      deviations from the body weight standard (underweight, overweight and obesity)
      among 4-18 years old children, adolescents and youths of Minsk, Belarus examined
      in the period 2001-2008. Subjects and methods: The measurements of 2969 children,
      teenagers and young adults carried out in the period 2001-2008 were used.
      Children were classified as underweight, normal weight, overweight and obese
      using Body Mass Index (BMI) cutoff points proposed by IOTF. Results: Underweight
      was recorded more often in girls (10.7%) than in boys (7.5%), differences are
      significant (p < 0.05). More frequent occurrence of underweight was typical for
      girls and boys of older age periods (11-18 years) - 11.6-14.2% and 8.9-9.6%,
      respectively. Overweight was found in boys and girls with the same frequency
      (10.9 and 10.7%, respectively). Obesity was more often observed in boys than in
      girls (2.3 and 1.8%). An increase in the proportion of overweight children
      (especially intensive in boys) was observed before the pubertal growth spurt.
      Conclusion: Our analysis showed a fairly low percentage of deviations from the
      standard body weight. The considerable variability of the data on the prevalence
      of overweight and obesity in children of Belarus obtained by different authors
      can be related both to differences in levels of living in different regions of
      the country and fairly rapid changes in this area due to socio-economic changes
      in society.

PMID- 29322161
TI  - Lithium and Dementia-Reply.

PMID- 29322162
TI  - Lithium and Dementia.

PMID- 29322163
TI  - Pragmatic Psychiatric Epidemiology-If You Can't Count It, It Won't Count.

PMID- 29322164
TI  - Efficacy of Transdermal Estradiol and Micronized Progesterone in the Prevention
      of Depressive Symptoms in the Menopause Transition: A Randomized Clinical Trial.
AB  - Importance: The menopause transition and early postmenopausal period are
      associated with a 2- to 4-fold increased risk for clinically significant
      depressive symptoms. Although a few studies suggest that hormone therapy can
      effectively manage existing depression during this time, to our knowledge, there
      have been no studies testing whether hormone therapy can prevent the onset of
      perimenopausal and early postmenopausal depressive symptoms. Objective: To
      examine the efficacy of transdermal estradiol plus intermittent micronized
      progesterone (TE+IMP) in preventing depressive symptom onset among initially
      euthymic perimenopausal and early postmenopausal women. A secondary aim was to
      identify baseline characteristics predicting TE+IMP's beneficial mood effects.
      Design, Setting, and Participants: Double-blind, placebo-controlled randomized
      trial at the University of North Carolina at Chapel Hill from October 2010 to
      February 2016. Participants included euthymic perimenopausal and early
      postmenopausal women from the community, aged 45 to 60 years. Interventions:
      Transdermal estradiol (0.1 mg/d) or transdermal placebo for 12 months. Oral
      micronized progesterone (200 mg/d for 12 days) was also given every 3 months to
      women receiving active TE, and identical placebo pills were given to women
      receiving placebo. Main Outcome Measures: Scores on the Center for
      Epidemiological Studies-Depression Scale (CES-D), assessed at baseline and months
      1, 2, 4, 6, 8, 10, and 12 after randomization, and the incidence of clinically
      significant depressive symptoms, defined as a CES-D score of at least 16.
      Results: Of 172 participants, 130 were white (76%), and 70 were African American
      (19%), with a mean household income of $50 000 to $79 999. The mean age was 51
      years, and 43 developed clinically significant depressive symptoms. Women
      assigned to placebo were more likely than those assigned to TE+IMP to score at
      least 16 on the CES-D at least once during the intervention phase (32.3% vs
      17.3%; odds ratio [OR], 2.5; 95% CI, 1.1-5.7; P = .03) and had a higher mean CES
      D score across the intervention period (P = .03). Baseline reproductive stage
      moderated the effect of treatment (beta, -1.97; SEM, 0.80; P for the interaction
      = .03) such that mood benefits of TE+IMP vs placebo were evident among women in
      the early menopause transition (beta, -4.2; SEM, 1.2; P < .001) but not the late
      menopause transition (beta, -0.9; SEM, 0.3; P = .23) or among postmenopausal
      women (beta, -0.3; SEM, 1.1; P = .92). Stressful life events in the 6 months
      preceding enrollment also moderated the effect of treatment on mean CES-D score
      such that the mood benefits of TE+IMP increased with a greater number of events
      (beta, 1.22; SEM, 0.40; P = .003). Baseline estradiol levels, baseline vasomotor
      symptoms, history of depression, and history of abuse did not moderate treatment
      effects. Conclusions: Twelve months of TE+IMP were more effective than placebo in
      preventing the development of clinically significant depressive symptoms among
      initially euthymic perimenopausal and early postmenopausal women. Trial
      Registration: clinicaltrials.gov Identifier: NCT01308814.

PMID- 29322165
TI  - Visual search in barn owls: Task difficulty and saccadic behavior.
AB  - How do we find what we are looking for? A target can be in plain view, but it may
      be detected only after extensive search. During a search we make directed
      attentional deployments like saccades to segment the scene until we detect the
      target. Depending on difficulty, the search may be fast with few attentional
      deployments or slow with many, shorter deployments. Here we study visual search
      in barn owls by tracking their overt attentional deployments-that is, their head
      movements-with a camera. We conducted a low-contrast feature search, a high
      contrast orientation conjunction search, and a low-contrast orientation
      conjunction search, each with set sizes varying from 16 to 64 items. The barn
      owls were able to learn all of these tasks and showed serial search behavior. In
      a subsequent step, we analyzed how search behavior of owls changes with search
      complexity. We compared the search mechanisms in these three serial searches with
      results from pop-out searches our group had reported earlier. Saccade amplitude
      shortened and fixation duration increased in difficult searches. Also, in
      conjunction search saccades were guided toward items with shared target features.
      These data suggest that during visual search, barn owls utilize mechanisms
      similar to those that humans use.

PMID- 29322166
TI  - Lithium and Dementia.

PMID- 29322167
TI  - Use of High-Risk Coronary Atherosclerotic Plaque Detection for Risk
      Stratification of Patients With Stable Chest Pain: A Secondary Analysis of the
      PROMISE Randomized Clinical Trial.
AB  - Importance: Coronary computed tomographic angiography (coronary CTA) can
      characterize coronary artery disease, including high-risk plaque. A noninvasive
      method of identifying high-risk plaque before major adverse cardiovascular events
      (MACE) could provide practice-changing optimizations in coronary artery disease
      care. Objective: To determine whether high-risk plaque detected by coronary CTA
      was associated with incident MACE independently of significant stenosis (SS) and
      cardiovascular risk factors. Design, Setting, and Participants: This prespecified
      nested observational cohort study was part of the Prospective Multicenter Imaging
      Study for Evaluation of Chest Pain (PROMISE) trial. All stable, symptomatic
      outpatients in this trial who required noninvasive cardiovascular testing and
      received coronary CTA were included and followed up for a median of 25 months.
      Exposures: Core laboratory assessment of coronary CTA for SS and high-risk plaque
      (eg, positive remodeling, low computed tomographic attenuation, or napkin-ring
      sign). Main Outcomes and Measures: The primary end point was an adjudicated
      composite of MACE (defined as death, myocardial infarction, or unstable angina).
      Results: The study included 4415 patients, of whom 2296 (52%) were women, with a
      mean age of 60.5 years, a median atherosclerotic cardiovascular disease (ASCVD)
      risk score of 11, and a MACE rate of 3% (131 events). A total of 676 patients
      (15.3%) had high-risk plaques, and 276 (6.3%) had SS. The presence of high-risk
      plaque was associated with a higher MACE rate (6.4% vs 2.4%; hazard ratio, 2.73;
      95% CI, 1.89-3.93). This association persisted after adjustment for ASCVD risk
      score and SS (adjusted hazard ratio [aHR], 1.72; 95% CI, 1.13-2.62). Adding high
      risk plaque to the ASCVD risk score and SS assessment led to a significant
      continuous net reclassification improvement (0.34; 95% CI, 0.02-0.51). Presence
      of high-risk plaque increased MACE risk among patients with nonobstructive
      coronary artery disease relative to patients without high-risk plaque (aHR, 4.31
      vs 2.64; 95% CI, 2.25-8.26 vs 1.49-4.69). There were no significant differences
      in MACE in patients with SS and high-risk plaque as opposed to those with SS but
      not high-risk plaque (aHR, 8.68 vs. 9.31; 95% CI, 4.25-17.73 vs 4.21-20.61). High
      risk plaque was a stronger predictor of MACE in women (aHR, 2.41; 95% CI, 1.25
      4.64) vs men (aHR, 1.40; 95% CI, 0.81-2.39) and younger patients (aHR, 2.33; 95%
      CI, 1.20-4.51) vs older ones (aHR, 1.36; 95% CI, 0.77-2.39). Conclusions and
      Relevance: High-risk plaque found by coronary CTA was associated with a future
      MACE in a large US population of outpatients with stable chest pain. High-risk
      plaque may be an additional risk stratification tool, especially in patients with
      nonobstructive coronary artery disease, younger patients, and women. The
      importance of findings is limited by low absolute MACE rates and low positive
      predictive value of high-risk plaque. Trial Registration: clinicaltrials.gov
      Indentifier: NCT01174550.

PMID- 29322169
TI  - Intertriginous Condyloma-like Plaques and Ulcers.

PMID- 29322170
TI  - Optimal Use of Preoperative Imaging in Primary Hyperparathyroidism.

PMID- 29322168
TI  - Patient Preferences for Surgery or Antibiotics for the Treatment of Acute
      Appendicitis.
AB  - Importance: Studies have compared surgical with nonsurgical therapy for acute
      uncomplicated appendicitis, but none of these studies have a patient-centered
      perspective. Objectives: To evaluate how patients might choose between surgical
      and nonsurgical therapy for acute uncomplicated appendicitis and to identify
      targets to make antibiotic treatment more appealing. Design, Setting, and
      Participants: This study comprised an online survey and an in-person sensitivity
      analysis survey. For the web survey, a convenience sample of 1728 respondents
      were asked to imagine that they or their child had acute uncomplicated
      appendicitis, provided information about laparoscopic and open appendectomy and
      antibiotic treatment alone, and asked which treatment they might choose. The web
      survey was open from April 17, 2016, through June 16, 2016, and was disseminated
      via email link, a poster with a Quick Response code, and social media. For the
      sensitivity analysis, 220 respondents were given the same scenario and options.
      Those who chose surgery were asked whether certain factors influenced their
      decision; each factor was incrementally improved during questioning about whether
      respondents would consider switching to antibiotics. These participants were
      recruited at public venues from June 3, 2016, to July 31, 2016. Web survey data
      were analyzed from June 17, 2016, to September 21, 2017. Sensitivity analysis
      data were analyzed from August 1, 2016, to September 21, 2017. Main Outcomes and
      Measures: Treatment preferences. Results: Among the 1728 web survey respondents,
      1225 (70.9%) were female and 500 (28.9%) were male (3 [0.2%] either did not
      answer or responded as "gender fluid" within the comments section of the survey),
      and most self-reported being between 50 and 59 years of age (391 [22.6%]) and
      being non-Hispanic white (1563 [90.5%]). For themselves, 1482 respondents (85.8%)
      chose laparoscopic appendectomy, 84 (4.9%) chose open appendectomy, and 162
      (9.4%) chose antibiotics alone. For their child, 1372 respondents (79.4%) chose
      laparoscopic appendectomy, 106 (6.1%) open appendectomy, and 250 (14.5%)
      antibiotics alone. Respondents were somewhat more likely to choose antibiotics
      for themselves if they had education beyond college (105 [12.6%]; P < .001),
      identified as other than non-Hispanic white (24 [14.9%]; P < .001), or did not
      know anyone who had previously been hospitalized (12 [15.8%]; P = .02), but they
      were less likely to choose antibiotics if they were surgeons (11 [5.4%]; P =
      .008). Of the 220 participants interviewed for the sensitivity analysis, 120
      (54.5%) were female and 100 (45.5%) were male, and most self-reported being
      between 18 and 24 years of age (53 [24.1%]) and being non-Hispanic white (204
      [92.7%]). Their responses suggested that improvements in the short- and long-term
      failure rate of antibiotic treatment-rather than reductions in the duration of
      hospitalization or antibiotic treatment-were more likely to increase the
      desirability of choosing antibiotics. Conclusions and Relevance: Most patients
      may choose surgical intervention over antibiotics alone in treatment of acute
      uncomplicated appendicitis, but a meaningful number may choose nonoperative
      management. Therefore, from a patient-centered perspective, this option should be
      discussed with patients, and future research could be directed at reducing the
      failure and recurrence rates of antibiotic treatment for appendicitis.

PMID- 29322171
TI  - Optimal Use of Preoperative Imaging in Primary Hyperparathyroidism-Reply.

PMID- 29322172
TI  - Palliative Care Assessment in the Surgical and Trauma Intensive Care Unit.

PMID- 29322173
TI  - Association of Surgical Practice Patterns and Clinical Outcomes With Surgeon
      Training in University- or Nonuniversity-Based Residency Program.
AB  - Importance: Important metrics of residency program success include the clinical
      outcomes achieved by trainees after transitioning to practice. Previous studies
      have shown significant differences in reported training experiences of general
      surgery residents at nonuniversity-based residency (NUBR) and university-based
      residency (UBR) programs. Objective: To examine the differences in practice
      patterns and clinical outcomes between surgeons trained in NUBR and those trained
      in UBR programs. Design, Setting, and Participants: This observational cohort
      study linked the claims data of patients who underwent general surgery procedures
      in New York, Florida, and Pennsylvania between January 1, 2012, and December 31,
      2013, to demographic and training information of surgeons in the American Medical
      Association Physician Masterfile. Patients who underwent a qualifying procedure
      were grouped by surgeon. Practice pattern analysis was performed on 3638 surgeons
      and 1 237 621 patients, representing 214 residency programs. Clinical outcomes
      analysis was performed on 2301 surgeons and 312 584 patients. Data analysis was
      conducted from February 1, 2017, to July 31, 2017. Exposures: NUBR or UBR
      training status. Main Outcomes and Measures: Inpatient mortality, complications,
      and prolonged length of stay. Results: No significant differences were observed
      between the NUBR-trained surgeons and UBR-trained surgeons in age (mean, 53.3
      years vs 53.7 years), sex (female, 18.2% vs 16.9%), or years of clinical
      experience (mean, 16.5 years vs 16.5 years). Overall, NUBR-trained surgeons
      compared with UBR-trained surgeons performed more procedures (median
      interquartile range [IQR], 328 [93-661] vs 164 [49-444]; P < .001) and performed
      a greater proportion of procedures in the outpatient setting (risk difference,
      6.5; 95% CI, 6.4 to 6.7; P < .001). Before matching, the mean proportion of
      patients with documented inpatient mortality was lower for NUBR-trained surgeons
      than for UBR-trained surgeons (risk difference, -1.01; 95% CI, -1.41 to -0.61; P
      < .001). The mean proportion of patients with complications (risk difference, 
      3.17%; 95% CI, -4.21 to -2.13; P < .001) and prolonged length of stay (risk
      difference, -1.89%; 95% CI, -2.79 to -0.98; P < .001) was also lower for NUBR
      trained surgeons. After matching, no significant differences in patient
      mortality, complications, and prolonged length of stay were found between NUBR-
      and UBR-trained surgeons. Conclusions and Relevance: Surgeons trained in NUBR and
      UBR programs have distinct practice patterns. After controlling for patient,
      procedure, and hospital factors, no differences were observed in the inpatient
      outcomes between the 2 groups.

PMID- 29322174
TI  - Human Herpesvirus 8-Associated Inflammatory Cytokine Syndrome.

PMID- 29322176
TI  - Omitted Conflict of Interest Disclosures.

PMID- 29322177
TI  - High-Risk Coronary Atherosclerotic Plaque Assessment by Coronary Computed
      Tomography Angiography-Should We Use It?

PMID- 29322175
TI  - Association of Psoriasis With Comorbidity Development in Children With Psoriasis.
AB  - Importance: Children with psoriasis are at increased risk for comorbidities. Many
      children with psoriasis are also overweight or obese; it is unknown whether the
      increased risk of comorbidities in these children is independent of obesity.
      Objective: To determine the risk of elevated lipid levels
      (hyperlipidemia/hypertriglyceridemia), hypertension, metabolic syndrome,
      polycystic ovarian syndrome, diabetes, nonalcoholic liver disease, and elevated
      liver enzyme levels in children with and without psoriasis, after accounting for
      obesity. Design, Setting, and Participants: This was a retrospective cohort study
      of claims data from Optum Laboratories Data Warehouse (includes 150 million
      privately insured and Medicare enrollees). A cohort of 29 957 children with
      psoriasis (affected children) and an age-, sex-, and race-matched comparator
      cohort of 29 957 children without psoriasis were identified and divided into 4
      groups: (1) nonobese, without psoriasis (reference cohort); (2) nonobese, with
      psoriasis; (3) obese, without psoriasis; and (4) obese, with psoriasis. Main
      Outcomes and Measures: Risk of developing comorbidities (Cox proportional hazards
      regression). Results: The overall mean (SD) age of those included in the cohort
      was 12.0 (4.4) years, and 16 034 (53.5%) were girls. At baseline, more affected
      children were obese (862 [2.9%] vs 463 [1.5%]; P < .001 for all comparisons).
      Children with psoriasis were significantly more likely to develop each of the
      comorbidities than those without psoriasis (P < .01). Obesity was a strong risk
      factor for development of each comorbidity, even in those without psoriasis
      (hazard ratios [HRs] ranging from 2.26 to 18.11). The risk of comorbidities was
      40% to 75% higher among nonobese children with vs without psoriasis: elevated
      lipid levels (HR, 1.42; 95% CI, 1.25-1.62), hypertension (HR, 1.64; 95% CI, 1.40
      1.93), diabetes (HR, 1.58; 95% CI, 1.27-1.95), metabolic syndrome (HR, 1.62; 95%
      CI, 1.13-2.33), polycystic ovarian syndrome (HR, 1.49; 95% CI, 1.18-1.88),
      nonalcoholic liver disease (HR, 1.76; 95% CI, 1.16-2.65), and elevated liver
      enzyme levels (HR, 1.46; 95% CI, 1.27-1.67). Except for hypertension (P = .03),
      no significant interaction occurred between psoriasis and obesity on the risk of
      comorbidities. Conclusions and Relevance: Children with psoriasis are at greater
      risk of developing obesity, hyperlipidemia, hypertension, diabetes, metabolic
      syndrome, polycystic ovarian syndrome, nonalcoholic liver disease, and elevated
      liver function enzyme levels than children without psoriasis. While psoriasis is
      a small independent risk factor for the development of these comorbidities,
      obesity is a much stronger contributor to comorbidity development in children
      with psoriasis.

PMID- 29322179
TI  - Nonuniversity-Based Surgeons Coming Up Anything but Short in Solutions to the
      Future Surgeon Shortage.

PMID- 29322178
TI  - Early Genetic Diagnosis of Neurofibromatosis Type 2 From Skin Plaque Plexiform
      Schwannomas in Childhood.
AB  - Importance: Neurofibromatosis type 2 (NF2) is a devastating genetic condition
      characterized by the development of multiple tumors of the nervous system. An
      early diagnosis of individuals with NF2 would facilitate treatment and reduction
      of disease impact because most severe effects of the disease do not usually
      develop before adolescence. Little attention has traditionally been paid to
      dermatological signs in NF2. However, skin plaques are commonly seen in patients
      with NF2, normally appearing either at birth or early childhood, providing an
      opportunity for early NF2 detection and testing. Objective: To determine the
      clinical utility of skin plaque identification and characterization in children
      for reaching an early diagnosis of patients with NF2 and to evaluate their
      molecular pathogenesis and their use in the genetic diagnostics of NF2. Design,
      Setting, and Participants: Diagnostic test study by the histological and genetic
      characterization of skin plaques from patients with NF2. Patients were 7
      individuals with NF2 or clinical suspicion of NF2 treated at the Spanish
      Reference Center on Phakomatoses. Main Outcomes and Measures: Histological
      evaluation of all skin plaques was performed. Fresh skin plaques were cultured to
      obtain Schwann cells and the NF2 gene was genetically analyzed. For all 7
      patients, NF2 clinical history was reviewed. Results: In all 7 patients (4 male
      and 3 female), all skin plaques analyzed were histologically characterized as
      plexiform schwannomas. Genetic analysis of primary Schwann cell cultures derived
      from them allowed the identification of a constitutional and a somatic NF2
      mutation. Genetic testing allowed the early diagnosis of NF2 in a child only
      exhibiting the presence of skin plaques. Most of the patients with NF2 analyzed
      had an early presentation of skin plaques and a severe NF2 phenotype. Conclusions
      and Relevance: This work emphasizes the clinical utility of a careful
      dermatological inspection and the correct identification of skin plaques in
      children for an early diagnosis of NF2. We show for the first time that Schwann
      cells derived from skin plaque plexiform schwannomas bear the double inactivation
      of the NF2 gene and thus constitute an excellent source of tissue for genetic
      testing, especially in the context of mosaicism.

PMID- 29322180
TI  - Should Hormone Therapy Be Used to Prevent Depressive Symptoms During the
      Menopause Transition?

PMID- 29322181
TI  - Best Practice for Developmental Stuttering: Balancing Evidence and Expertise.
AB  - Purpose: Best practice for developmental stuttering remains a topic of debate. In
      the clinical forum following this introduction, four fluency experts balance the
      evidence and expertise to describe their approach to assessment and treatment.

PMID- 29322182
TI  - Evidence, Goals, and Outcomes in Stuttering Treatment: Applications With an
      Adolescent Who Stutters.
AB  - Purpose: The purpose of this clinical focus article is to summarize 1 possible
      process that a clinician might follow in designing and conducting a treatment
      program with John, a 14-year-old male individual who stutters. Method: The
      available research evidence, practitioner experience, and consideration of
      individual preferences are combined to address goals, treatment procedures, and
      outcomes for John. Conclusions: The stuttering treatment research literature
      includes multiple well-designed reviews and individual studies that have shown
      the effectiveness of prolonged speech (and smooth speech and related variations)
      for improving stuttered speech and for improving social, emotional, cognitive,
      and related variables in adolescents who stutter. Based on that evidence, and
      incorporating the additional elements of practitioner experience and client
      preferences, this clinical focus article suggests that John would be likely to
      benefit from a treatment program based on prolonged speech. The basic structure
      of 1 possible such program is also described, with an emphasis on the goals and
      outcomes that John could be expected to achieve.

PMID- 29322184
TI  - Comprehensive Stuttering Treatment for Adolescents: A Case Study.
AB  - Purpose: This article will focus on a hypothetical case study to highlight
      comprehensive assessment and treatment for adolescent children who stutter.
      Method: Assessment and treatment are laid out with a literature review utilizing
      the components of the International Classification of Functioning, Disability and
      Health model. Specific assessment and treatment strategies and approaches are
      discussed. Results: Using the International Classification of Functioning,
      Disability and Health model can help guide clinicians through the assessment and
      treatment process to ensure that all areas of stuttering are considered.
      Conclusion: Comprehensive assessment and treatment helps clinicians address all
      relevant elements of a stuttering disorder, rather than focusing exclusively on
      reducing speech disruptions.

PMID- 29322186
TI  - Stuttering in Preschool Children: Direct Versus Indirect Treatment.
AB  - Purpose: The purpose of this article is to discuss the controversial topic of
      stuttering in preschool children and how to evaluate the options for treatment,
      emphasizing the role of external research evidence. Method: A hypothetical but
      realistic case study of a 3-year-old boy who stutters is described. Two
      contrasting approaches to treatment are presented, the Lidcombe Program (LP) and
      the demands and capacities model (DCM). Studies published in peer-reviewed
      research journals that have examined the effectiveness of each approach are
      summarized and critiqued. Results: The review indicates that the LP is the
      preferred treatment approach for stuttering in preschool children and that it
      offers the best opportunity for rapid success. Conclusion: The LP should be
      carried out by knowledgeable, experienced, and flexible speech-language
      pathologists who are able to accommodate the individual needs and differences of
      every child and family.

PMID- 29322187
TI  - Incorrect Data Presentation and Figure Citations.

PMID- 29322185
TI  - Selecting Treatments and Monitoring Outcomes: The Circle of Evidence-Based
      Practice and Client-Centered Care in Treating a Preschool Child Who Stutters.
AB  - Purpose: The purpose of the present clinical forum is to compare how 2 clinicians
      might select among therapy options for a preschool-aged child who presents with
      stuttering close to onset. Method: I discuss approaches to full evaluation of the
      child's profile, advisement of evidence-based practice options open to the
      family, the need for monitoring of the child's response, and selection of other
      approaches, if the child appears nonresponsive to the 1st-line approach. Results:
      Although some researchers and clinicians appear to favor endorsement of a single
      recommended treatment for early stuttering, I do not find this approach helpful
      or consistent with newer mandates for patient-centered care. I am also most
      comfortable recommending RESTART demands and capacities model as the 1st
      treatment approach, with parent consent, because its mechanism of action appears
      transparent and well-documented. Conclusions: There are numerous well-supported
      intervention options for treating preschool children who stutter. No single
      therapy can possibly work for all clients. I discuss available options that I
      feel have sufficient evidence-based support for use with young children who
      stutter. I emphasize the need to consider more, not fewer, acceptable therapy
      options for children who do not respond positively to a selected treatment
      approach within a reasonable time frame.

PMID- 29322188
TI  - Management of Morgellons Disease With Low-Dose Trifluoperazine.

PMID- 29322189
TI  - Error in Figure Legend.

PMID- 29322191
TI  - The Himba and Red Ochre-Aesthetics, Symbolism, and Adaptation.

PMID- 29322193
TI  - To Nitpick.

PMID- 29322192
TI  - A Memorable Touch.

PMID- 29322194
TI  - Spanish Fly-Cantharidin's Alter Ego.

PMID- 29322195
TI  - Sporty Spots.

PMID- 29322196
TI  - Dermatology's Grandest Piano.

PMID- 29322199
TI  - The impact of socioeconomic status on the association between biomedical and
      psychosocial well-being and all-cause mortality in older Spanish adults.
AB  - PURPOSE: The aim of this paper was to analyze the effect of biomedical and
      psychosocial well-being, based on distinct successful aging models (SA), on time
      to mortality, and determine whether this effect was modified by socioeconomic
      status (SES) in a nationally representative sample of older Spanish adults.
      METHODS: Data were taken from a 3-year follow-up study with 2783 participants
      aged 50 or over. Vital status was ascertained using national registers or asking
      participants' relatives. Kaplan-Meier curves were used to estimate the time to
      death by SES, and levels of biomedical and psychosocial SA. Cox proportional
      hazard regression models were conducted to explore interactions between SES and
      SA models while adjusting for gender, age, and marital status. RESULTS: Lower
      levels of SES and biomedical and psychosocial SA were associated with low
      probability of survival. Only the interaction between SES and biomedical SA was
      significant. Biomedical SA impacted on mortality rates among individuals with low
      SES but not on those with medium or high SES, whereas psychosocial SA affected
      mortality regardless of SES. CONCLUSIONS: Promoting equal access to health care
      system and improved psychosocial well-being could be a protective factor against
      premature mortality in older Spanish adults with low SES.

PMID- 29322200
TI  - Prospective associations between recalled parental bonding and perinatal
      depression: a cohort study in urban and rural Turkey.
AB  - PURPOSE: Recalled experiences of parental bonding may be important in the
      aetiology of perinatal depression. We hypothesized that lower recalled parental
      bonding would be associated with perinatal depression. METHOD: In a cohort study
      of perinatal depression in Turkey, 677 women were recruited in their third
      trimester. Parental Bonding Inventory (PBI) scores at baseline were investigated
      as predictors of depression on the Edinburgh Postnatal Depression Scale (EPDS) at
      4, 14 and 21 months after childbirth in mothers without depression at baseline.
      RESULTS: Poor parental bonding scores, apart from paternal control and
      overprotection, were independently associated with antenatal depression. Incident
      postnatal depression at 4 months was predicted by parental overprotection, at 14
      months by parental care and overprotection, and at 21 months by paternal control
      and overprotection. CONCLUSIONS: Less satisfactory parenting recalled in the
      antenatal period was an independent predictor of postnatal depression; however,
      the different bonding subscales varied as predictors according to the timing of
      the depression assessment after childbirth.

PMID- 29322201
TI  - Characterization of corticospinal activation of finger motor neurons during
      precision and power grip in humans.
AB  - Direct and indirect corticospinal pathways to finger muscles may play a different
      role in control of the upper extremity. We used transcranial magnetic stimulation
      (TMS) and coherence analysis to characterize the corticospinal drive to the first
      dorsal interosseous (FDI) and abductor pollicis brevis (APB) when active during a
      precision and power grip task. In experiment 1, single motor units were recorded
      during precision grip and power grip in 20 adults (25.2 +/- 7.1 years). Post
      stimulus time histograms (PSTH) were obtained following TMS. In experiment 2,
      coherence and cross-correlation analysis of the FDI and APB surface EMG were used
      to investigate the temporal organization of corticospinal drive during precision
      grip and power grip in 15 adults (27.4 +/- 8.1 years). We found no significant
      differences in PSTH peak onset (26.6 +/- 1.9 vs. 26.7 +/- 2.0 ms, p = 0.75),
      maximal peak (27.4 +/- 1.9 vs. 27.4 +/- 1.9 ms, p = 1.0) or peak duration (2.3 +/
      1.1 vs. 2.3 +/- 1.0 ms, p = 0.75) for the 11 recovered motor units during
      precision grip and power grip. Also, no significant difference in coherence or
      the width of the synchronization peaks during precision grip (7.2 +/- 3.7 ms) and
      power grip (7.9 +/- 3.1 ms) could be observed (p = 0.59). The short duration of
      peaks elicited in the PSTH of single motor units following TMS and central
      synchronization peaks of voluntarily activated motor units during precision and
      power grip suggests that the direct corticospinal pathway (the
      corticomotoneuronal system) is equally involved in the control of both tasks. The
      data do not support that indirect pathways would make a larger contribution to
      power grip.

PMID- 29322198
TI  - Association of Cardiovascular Biomarkers With Incident Heart Failure With
      Preserved and Reduced Ejection Fraction.
AB  - Importance: Nearly half of all patients with heart failure have preserved
      ejection fraction (HFpEF) as opposed to reduced ejection fraction (HFrEF), yet
      associations of biomarkers with future heart failure subtype are incompletely
      understood. Objective: To evaluate the associations of 12 cardiovascular
      biomarkers with incident HFpEF vs HFrEF among adults from the general population.
      Design, Setting, and Participants: This study included 4 longitudinal community
      based cohorts: the Cardiovascular Health Study (1989-1990; 1992-1993 for
      supplemental African-American cohort), the Framingham Heart Study (1995-1998),
      the Multi-Ethnic Study of Atherosclerosis (2000-2002), and the Prevention of
      Renal and Vascular End-stage Disease study (1997-1998). Each cohort had
      prospective ascertainment of incident HFpEF and HFrEF. Data analysis was
      performed from June 25, 2015, to November 9, 2017. Exposures: The following
      biomarkers were examined: N-terminal pro B-type natriuretic peptide or brain
      natriuretic peptide, high-sensitivity troponin T or I, C-reactive protein (CRP),
      urinary albumin to creatinine ratio (UACR), renin to aldosterone ratio, D-dimer,
      fibrinogen, soluble suppressor of tumorigenicity, galectin-3, cystatin C,
      plasminogen activator inhibitor 1, and interleukin 6. Main Outcomes and Measures:
      Development of incident HFpEF and incident HFrEF. Results: Among the 22 756
      participants in these 4 cohorts (12 087 women and 10 669 men; mean [SD] age, 60
      [13] years) in the study, during a median follow-up of 12 years, 633 participants
      developed incident HFpEF, and 841 developed HFrEF. In models adjusted for
      clinical risk factors of heart failure, 2 biomarkers were significantly
      associated with incident HFpEF: UACR (hazard ratio [HR], 1.33; 95% CI, 1.20-1.48;
      P < .001) and natriuretic peptides (HR, 1.27; 95% CI, 1.16-1.40; P < .001), with
      suggestive associations for high-sensitivity troponin (HR, 1.11; 95% CI, 1.03
      1.19; P = .008), plasminogen activator inhibitor 1 (HR, 1.22; 95% CI, 1.03-1.45;
      P = .02), and fibrinogen (HR, 1.12; 95% CI, 1.03-1.22; P = .01). By contrast, 6
      biomarkers were associated with incident HFrEF: natriuretic peptides (HR, 1.54;
      95% CI, 1.41-1.68; P < .001), UACR (HR, 1.21; 95% CI, 1.11-1.32; P < .001), high
      sensitivity troponin (HR, 1.37; 95% CI, 1.29-1.46; P < .001), cystatin C (HR,
      1.19; 95% CI, 1.11-1.27; P < .001), D-dimer (HR, 1.22; 95% CI, 1.11-1.35; P <
      .001), and CRP (HR, 1.19; 95% CI, 1.11-1.28; P < .001). When directly compared,
      natriuretic peptides, high-sensitivity troponin, and CRP were more strongly
      associated with HFrEF compared with HFpEF. Conclusions and Relevance: Biomarkers
      of renal dysfunction, endothelial dysfunction, and inflammation were associated
      with incident HFrEF. By contrast, only natriuretic peptides and UACR were
      associated with HFpEF. These findings highlight the need for future studies
      focused on identifying novel biomarkers of the risk of HFpEF.

PMID- 29322202
TI  - High-flow nasal cannula oxygen therapy for acute hypoxemic respiratory failure in
      patients with chronic lung disease in terms of hospital outcomes.

PMID- 29322203
TI  - Program death inhibitors in classical Hodgkin's lymphoma: a comprehensive review.
AB  - Cancer cells are able to induce immune system tolerance through different
      mechanisms. Recent achievements in the understanding of tumor microenvironment,
      invasion, and metastasizing have contributed to accelerated drug developments and
      approvals. Hodgkin lymphoma (HL) cells are the minority in a lymphocyte-rich
      microenvironment of HL tissue. The program death-1 (PD-1)/PD-ligand-1 checkpoint
      is one of the known effective pathways in classical HL to escape the immune
      system cells. The approval of PD-1 inhibitors in different cancer types with
      exciting response rates is truly revolutionizing our treatment armamentarium
      against cancer in general and classical HL in specific. Although the disease is
      one of the most curable tumors, we still need better outcome with more gentle
      treatment, especially for relapsed and refractory (r/r) patients. In this
      article, we review the current literature on immune checkpoint inhibitors and
      currently ongoing studies with nivolumab and pembrolizumab in r/r classical HL.

PMID- 29322206
TI  - [Perioperative handling of anticoagulation].
AB  - A growing number of patients in Germany receive a long-term prophylactic
      anticoagulation with phenprocoumone or one of the novel direct oral
      anticoagulants (NOAC), such as dabigatran, rivaroxaban or apixaban. The most
      common indication for an oral anticoagulant therapy is atrial fibrillation
      (approximately 75%) where the anticoagulant therapy can reduce the risk for an
      embolic event, particularly stroke by 60%. Operations carried out during such a
      therapy can result in major bleeding complications. On the other hand, suspending
      anticoagulant therapy can lead to an increased risk of thromboembolisms. Thus,
      the preoperative assessment should address the bleeding risk of the planned
      operation, the individual risk of thromboembolism, as well as other factors, such
      as patient age and renal function. If the individual assessment shows a
      substantial risk of perioperative bleeding when anticoagulant treatment is
      continued and a substantial risk of thromboembolism if the treatment is
      suspended, then a perioperative bridging, for example with low molecular weight
      heparin, is necessary. Perioperative bridging also leads to an increased risk of
      perioperative bleeding. Thus, undifferentiated bridging for all patients with
      atrial fibrillation with anticoagulant treatment is not recommended. Instead, the
      indications for a perioperative bridging should be decided according to
      individual risk profiles.

PMID- 29322207
TI  - [Global Health Care].
AB  - Global health data are changing rapidly and they show large regional differences.
      The incidence and mortality of infectious diseases can be reduced by successes in
      medical research, national health plans and large financial expenditure. In
      contrast, illnesses that are caused by unhealthy and changing environmental and
      living conditions are on the rise. The Global Health Care concept is a cross
      sectoral master plan taking into account that worldwide health cannot be
      established by healthcare workers alone. It was designed to have a lasting impact
      on the cause of disease through global health programs, of which improved medical
      services, including essential surgical treatment need to play a key role.

PMID- 29322205
TI  - The role of albumin-bilirubin grade and inflammation-based index in patients with
      hepatocellular carcinoma treated with stereotactic body radiotherapy.
AB  - PURPOSE: We evaluated the prognostic accuracy of the albumin-bilirubin (ALBI)
      grade and the inflammation-based index (IBI) in estimating overall survival (OS)
      and toxicity in patients with hepatocellular carcinoma (HCC) treated with
      stereotactic body radiotherapy (SBRT). MATERIALS AND METHODS: Forty patients with
      47 HCC lesions with a Barcelona Clinic Liver Cancer (BCLC) classification stage B
      or C were treated with SBRT in 3-12 fractions. The ALBI grade and the IBI were
      calculated at different time points (baseline, during, at the end of treatment
      and at follow-up) and compared with the Child-Pugh (CP) score as well as other
      patient- and treatment-related parameters, concerning OS and toxicity. RESULTS:
      The median follow-up was 14.3 months for patients alive. The median OS from SBRT
      was 10 (95% confidence interval 8.3-11.6) months. The local control at 1 year was
      79%. A lower IBI during treatment was associated with better OS (p = 0.034) but
      not CP and ALBI. Higher C-reactive protein levels as well as higher alpha
      fetoprotein concentrations correlated with worse survival (p = 0.001). Both
      higher ALBI (p = 0.02) and CTP (p = 0.001) at baseline correlated with a higher
      incidence of acute and late toxicities (CTC >=2). Neither the mean radiation dose
      to the liver nor the dose to 700 cc of the liver correlated with the occurrence
      of toxicities. CONCLUSIONS: In this analysis, a higher ALBI grade as well as a
      higher CP were predictors of higher incidence of toxicity, whereas a lower IBI
      during treatment correlated with a better OS. These results should be further
      evaluated in prospective studies.

PMID- 29322208
TI  - The association of the medial joint vacuum phenomenon with ulnar collateral
      ligament injury in symptomatic elbows of younger athletes.
AB  - OBJECTIVE: To determine the prevalence of intra-articular gas (IAG) on elbow
      radiography and evaluate variables, including IAG, as predictors of UCL injury.
      MATERIALS AND METHODS: This IRB-approved retrospective study consisted of 241
      consecutive elbow radiographic studies containing AP radiographs with valgus
      stress of both symptomatic and asymptomatic sides in 234 patients. The IAG,
      medial joint space (MJS), and MJS difference between the symptomatic and
      asymptomatic elbow (MJSD) were evaluated by two readers, as well as patient age,
      gender, sport played, and handedness. Primary outcomes included IAG on valgus
      stress radiographs and UCL injury, which was determined by intraoperative
      findings as the reference standard or MRI if surgery was not performed.
      Univariate analysis with Student's t, Fisher's exact, and chi-square tests were
      performed. RESULTS: IAG only manifested with valgus stress and was demonstrated
      in 30/482 (6.2%) valgus stress radiographs in 27/234 (11.5%) patients. Overall,
      21/241 (8.7%) valgus stress radiographs of the symptomatic elbow demonstrated IAG
      in 21 patients. A total of 128/241 (53.1%) elbow studies had evidence of UCL
      injury. MJS IAG (p = 0.0147) and increased MJSD (p = 0.0088) were significantly
      associated with UCL injury. Patient gender, age, handedness, laterality, sport
      played, and absolute MJS were not associated with UCL injury. MJS IAG with valgus
      stress demonstrates a sensitivity of 11.7% and specificity of 98.3% in detecting
      UCL injury for the symptomatic elbow. CONCLUSIONS: MJS IAG infrequently manifests
      on valgus stress radiographs, but is specific for UCL injury in the symptomatic
      elbow of overhead throwing athletes. MJS IAG and increased MJSD are significantly
      associated with UCL injury.

PMID- 29322209
TI  - Infiltrating angiolipoma of the foot: magnetic resonance imaging features and
      review of the literature.
AB  - Angiolipoma is a benign soft tissue tumor with two subtypes: non-infiltrating and
      infiltrating. Although histologically benign, infiltrating angiolipoma can invade
      surrounding structures. The foot is a very rare location for angiolipoma, with
      only four cases reported in the English literature, including one infiltrating
      type. Here, we report a very rare case of infiltrating angiolipoma of the foot
      with magnetic resonance imaging (MRI) and ultrasonography (US) findings. A 7-year
      old boy presented with a slowly growing foot mass. MRI showed an unencapsulated
      mass involving the third web space extending to the foot dorsum and sole. The
      mass was isointense to subcutaneous fat and was mixed with internal T1 low-signal
      intensity enhancing areas. On US, we observed a heterogeneously hypoechoic mass
      with internal vascularity. Imaging and clinical features of angiolipoma and the
      radiologic differential diagnoses of a fat-containing mass in the pediatric foot
      are reviewed here. When there is an ill-defined foot mass with a fat component
      and variable enhancing portions in a child, infiltrating angiolipoma should be
      included in the differential diagnosis along with other fat-containing tumors.

PMID- 29322204
TI  - Evolving notions on immune response in colorectal cancer and their implications
      for biomarker development.
AB  - INTRODUCTION: Colorectal cancer (CRC) still represents the third most commonly
      diagnosed type of cancer in men and women worldwide. CRC is acknowledged as a
      heterogeneous disease that develops through a multi-step sequence of events
      driven by clonal selections; this observation is sustained by the fact that
      histologically similar tumors may have completely different outcomes, including a
      varied response to therapy. METHODS: In "early" and "intermediate" stage of CRC
      (stages II and III, respectively) there is a compelling need for new biomarkers
      fit to assess the metastatic potential of their disease, selecting patients with
      aggressive disease that might benefit from adjuvant and targeted therapies.
      Therefore, we review the actual notions on immune response in colorectal cancer
      and their implications for biomarker development. RESULTS: The recognition of the
      key role of immune cells in human cancer progression has recently drawn attention
      on the tumor immune microenvironment, as a source of new indicators of tumor
      outcome and response to therapy. Thus, beside consolidated histopathological
      biomarkers, immune endpoints are now emerging as potential biomarkers.
      CONCLUSIONS: The introduction of immune signatures and cellular and molecular
      components of the immune system as biomarkers is particularly important
      considering the increasing use of immune-based cancer therapies as therapeutic
      strategies for cancer patients.

PMID- 29322210
TI  - Correction to: Dosimetry in clinical radionuclide therapy: the devil is in the
      detail.
AB  - The above article which was published in Volume 44/ Issue 12 has incorrect page
      numbers. Instead of 1-3, it should have been 2137-2139.

PMID- 29322211
TI  - "Within ring"-based sacroiliac rod fixation may overcome the weakness of
      spinopelvic fixation for unstable pelvic ring injuries: technical notes and
      clinical outcomes.
AB  - PURPOSE: Spinopelvic fixation and triangular osteosynthesis give firm internal
      fixation for unstable pelvic ring injuries (UPRI), but with sacrifice of mobility
      of the lumbar spine. Here, we describe the procedure and outcomes of a new
      approach, which we refer to as "within ring"-based sacroiliac rod fixation
      (SIRF). METHODS: The patient was placed in a prone position and longitudinal skin
      incisions were made at the medial margins of the bilateral posterior superior
      iliac spines (PSIS). After reduction of fracture, a pedicle screw was inserted
      into the first sacral vertebra on the injured side and iliac screws inserted
      through the bilateral PSIS were bridged using rods. RESULTS: SIRF was performed
      in 15 patients. The AO/OTA classification was 61-B2.3 in 1, C1.3 in 4, C2.3 in 7,
      C3.3 in 1, and H-type spinopelvic dissociation in two cases. The mean operative
      time was 179 (110-298) minutes, mean blood loss was 533 (100-2700) cc. One
      patient died during hospitalization and three patients stopped outpatient
      treatment. The other 11 patients achieved bone union without major loss of
      reduction in a mean post-operative follow-up period of 23.8 (4-50) months. The
      mean Majeed score at final follow-up was 86.7 (73-96) out of 96, excluding
      scoring sexual intercourse. CONCLUSIONS: "Within ring"-based SIRF not including
      the lumbar spine in the fixation range is a simple, safe, and low-invasive
      internal fixation method for UPRI.

PMID- 29322213
TI  - Translation and validation of the International Consultation on Incontinence
      Questionnaire Vaginal Symptoms (ICIQ-VS): the Danish version.
AB  - INTRODUCTION: In the clinical evaluation of women with pelvic organ prolapse
      (POP), it is important to evaluate both objective and subjective presentations.
      The objective evaluation is done by gynecological examination, but the subjective
      presentation is more complex. The International Consultation on Incontinence
      Questionnaire-Vaginal Symptoms (ICIQ-VS) is an important tool for subjective
      evaluation, and a Danish version was developed. MATERIALS AND METHODS: The
      English version was translated into Danish in accordance with guidelines. Eight
      women underwent a semistructured interview showing no misunderstandings. Women
      with and without prolapse completed the questionnaire and underwent a Pelvic
      Organ Prolapse Quantification (POP-Q) examination. Three weeks later a retest was
      done. Women undergoing prolapse surgery completed the questionnaire 3 months
      postoperatively. RESULTS: Ninety-four women with and 98 without prolapse were
      included; 52 underwent surgery. Retest response rate was 88-95%. Mean time
      between test and retest was 24.5 and 92.2 days, respectively. Missing data ranged
      between 0 and 1%. Test-retest reliability was good to excellent (ICC 0.61-0.88)
      and internal consistency was acceptable (Cronbach's alpha 0.79-0.84). The
      questionnaire was excellent when distinguishing between women with and without
      prolapse (p < 0.001). Criterion validity (correlation between POP-Q stage and the
      questionnaire) was perfect (p < 0.001). Sensitivity to change was excellent for
      vaginal symptom score and quality of life (p < 0.001) but not for sexual matters
      (p = 0.059). CONCLUSIONS: The Danish version of ICIQ-VS was successfully
      translated and can be a valuable tool for prolapse research and daily evaluation
      of patients.

PMID- 29322212
TI  - Meta-analysis on Materials and Techniques for Laparotomy Closure: The MATCH
      Review.
AB  - BACKGROUND: The aim of this systematic review and meta-analysis was to evaluate
      closure materials and suture techniques for emergency and elective laparotomies.
      The primary outcome was incisional hernia after 12 months, and the secondary
      outcomes were burst abdomen and surgical site infection. METHODS: A systematic
      literature search was conducted until September 2017. The quality of the RCTs was
      evaluated by at least 3 assessors using critical appraisal checklists. Meta
      analyses were performed. RESULTS: A total of 23 RCTs were included in the meta
      analysis. There was no evidence from RCTs using the same suture technique in both
      study arms that any suture material (fast-absorbable/slowly absorbable/non
      absorbable) is superior in reducing incisional hernias. There is no evidence that
      continuous suturing is superior in reducing incisional hernias compared to
      interrupted suturing. When using a slowly absorbable suture for continuous
      suturing in elective midline closure, the small bites technique results in
      significantly less incisional hernias than a large bites technique (OR 0.41; 95%
      CI 0.19, 0.86). CONCLUSIONS: There is no high-quality evidence available
      concerning the best suture material or technique to reduce incisional hernia rate
      when closing a laparotomy. When using a slowly absorbable suture and a continuous
      suturing technique with small tissue bites, the incisional hernia rate is
      significantly reduced compared with a large bites technique.

PMID- 29322215
TI  - [Assessment of kidney function : Creatinine is not the whole story].
AB  - Chronic renal insufficiency has a high prevalence and leads not only to a severe
      impairment in the quality of life but also to a higher mortality, mainly due to
      cardiovascular complications; however, in the early stages where there is still a
      chance for a therapeutic intervention, it is often underestimated because
      depending on endogenous factors (e.g. age and muscle mass), serum creatinine
      could falsely remain in the normal range while kidney function is already
      impaired. An exact measurement of the glomerular filtration rate (GFR) using
      radionuclide techniques is cumbersome and usually confined to rare cases, such as
      in clinical studies. Creatinine clearance measurement by 24-h urine collection
      requires good patient instructions and is error prone, thus it is limited to
      special circumstances. In routine clinical practice, estimation of the GFR by
      calculation algorithms provides the best approach. In recent years the chronic
      kidney disease epidemiology collaboration (CKD-EPI) formula has become
      established as the most accurate method. This should be used for screening and
      continuous surveillance. In addition, urinalysis including dipstick tests and
      urinary microscopy represent non-invasive, technically simple and economic
      screening tools. Due to its semiquantitative nature, the results of urinalysis
      should only to be interpreted after comprehensive consideration of the diagnostic
      and technical limitations, which are reviewed in this article.

PMID- 29322214
TI  - Protective role of Nrf2 against mechanical-stretch-induced apoptosis in mouse
      fibroblasts: a potential therapeutic target of mechanical-trauma-induced stress
      urinary incontinence.
AB  - INTRODUCTION AND HYPOTHESIS: We investigated the protective effect and underlying
      molecular mechanism of nuclear factor-E2-related factor 2 (Nrf2) against
      mechanical-stretch-induced apoptosis in mouse fibroblasts. METHODS: Normal cells,
      Nrf2 silencing cells, and Nrf2 overexpressing cells were respectively divided
      into two groups-nonintervention and cyclic mechanical strain (CMS)-subjected to
      CMS of 5333 MU (1.0 Hz for 4 h), six groups in total (control, CMS, shNfe212,
      shNfe212 + CMS, LV-shNfe212, and LV-shNfe212 + CMS). After treatment, cell
      apoptosis; cell-cycle distribution; expressions of Nrf2, Bax, Bcl-2, Cyt-C,
      caspase-3, caspase-9, cleaved-caspase-3, and cleaved-caspase-9; mitochondrial
      membrane potential (DeltaPsim); reactive oxygen species (ROS); and
      malondialdehyde (MDA) levels were measured. Thirty virgin female C57BL/6 mice
      were divided into two groups: control (without intervention) and vaginal
      distension (VD) groups, which underwent VD for 1 h with an 8-mm dilator (0.3 ml
      saline). Leak-point pressure (LPP) was tested on day 7 after VD; Nrf2 expression,
      apoptosis, and MDA levels were then measured in urethra and anterior vaginal
      wall. RESULTS: Mechanical stretch decreased Nrf2 messenger RNA (mRNA) and protein
      expressions. Overexpression of Nrf2 alleviated mechanical-stretch-induced cell
      apoptosis; S-phase arrest of cell cycle; up-regulation of Bax, cytochrome C (Cyt
      C), ROS, MDA, ratio of cleaved-caspase-3/caspase-3 and cleaved-caspase-9/caspase
      9; and exacerbated the decrease of Bcl2 and DeltaPsim in L929 cells. On the
      contrary, silencing of Nrf2 showed opposite effects. Besides, VD reduced LPP
      levels and Nrf2 expression and increased cell apoptosis and MDA generation in the
      urethra and anterior vaginal wall. CONCLUSIONS: Nrf2 exhibits a protective role
      against mechanical-stretch -induced apoptosis on mouse fibroblasts, which might
      indicate a potential therapeutic target of mechanical-trauma-induced stress
      urinary incontinence (SUI).

PMID- 29322216
TI  - [Therapy changes after stroke in patients with open foramen ovale? : Patent
      Foramen Ovale Closure or Anticoagulants versus Antiplatelet Therapy to Prevent
      Stroke Recurrence Trial (CLOSE), Randomized Evaluation of Recurrent Stroke
      Comparing PFO Closure to Established Current Standard of Care Treatment
      (RESPECT), and Carotid Revascularization Endarterectomy versus Stenting Trial
      (REDUCE)].

PMID- 29322217
TI  - [Functional diagnostics in pneumology].
AB  - Alongside imaging techniques, pulmonary function testing helps in the diagnosis
      of underlying disorders such as asthma and chronic obstructive pulmonary disease
      (COPD) or fibrosing lung disease. However, disease severity grading is also
      important, as well as disease follow-up under therapy. The value of spirometry as
      a first-line diagnostic test, whole-body plethysmography in advanced diagnostics,
      the measurement of transfer factor, as well as blood gas analysis are outlined.
      The importance of spiroergometry, echocardiography, and right-heart
      catheterization, particularly in the functional assessment of pulmonary vascular
      disorders, is described. Tests in respiratory sleep medicine, such as
      polysomnography, as well as tests for diagnosing chronic respiratory failure, are
      part of the respiratory physician's diagnostic armamentarium.

PMID- 29322218
TI  - [Paraneoplasms of the skin].
AB  - The cutaneous manifestations of malignancies include nonmalignant skin disorders
      that occur in association with malignancies (facultative paraneoplastic
      dermatoses) and skin disorders that are always associated with hematologic
      diseases or solid tumors (obligate paraneoplastic dermatoses). Paraneoplastic
      increase of growth factors or immunological reactions lead to a variety of
      inflammatory, hyperkeratotic or proliferative skin reactions. When paraneoplastic
      dermatoses develop before cancer is diagnosed, recognition of these skin diseases
      can accelerate both the diagnosis and treatment. The presence of unexplained
      cutaneous findings should lead to a multidisciplinary evaluation of the patient.
      This manuscript summarizes the cutaneous manifestations associated with
      hematologic disorders and solid tumors, their localization and treatment options.

PMID- 29322220
TI  - Diabetes and pregnancy: national trends over a 15 year period.
AB  - AIMS/HYPOTHESIS: We aimed to examine time trends in national perinatal outcomes
      in pregnancies complicated by pre-existing type 1 or type 2 diabetes. METHODS: We
      analysed episode-level data on all obstetric inpatient delivery events (live or
      stillbirth) between 1 April 1998 and 31 March 2013 (n = 813,921) using the
      Scottish Morbidity Record (SMR02). Pregnancies to mothers with type 1 (n = 3229)
      and type 2 (n = 1452) diabetes were identified from the national diabetes
      database (Scottish Care Information-Diabetes), and perinatal outcomes were
      compared among women with type 1 diabetes, type 2 diabetes and those without
      diabetes. RESULTS: The number of pregnancies complicated by diabetes increased
      significantly, by 44% in type 1 diabetes and 90% in type 2 diabetes, across the
      15 years examined, to rates of 1 in 210 and 1 in 504 deliveries, respectively.
      Compared with women without diabetes, delivery occurred 2.6 weeks earlier (type 1
      diabetes 36.7 +/- 2.3 weeks) and 2 weeks earlier (type 2 diabetes 37.3 +/- 2.4
      weeks), respectively, showing significant reductions for both type 1 (from 36.7
      weeks to 36.4 weeks, p = 0.03) and type 2 (from 38.0 weeks to 37.2 weeks, p <
      0.001) diabetes across the time period. The proportions of preterm delivery were
      markedly increased in women with diabetes (35.3% type 1 diabetes, 21.8% type 2
      diabetes, 6.1% without diabetes; p < 0.0001), and these proportions increased
      with time for both groups (p < 0.005). Proportions of elective Caesarean sections
      (29.4% type 1 diabetes, 30.5% type 2 diabetes, 9.6% without diabetes) and
      emergency Caesarean sections (38.3% type 1 diabetes, 29.1% type 2 diabetes, 14.6%
      without diabetes) were greatly increased in women with diabetes and increased
      over time except for stable rates of emergency Caesarean section in type 1
      diabetes. Gestational age-, sex- and parity-adjusted z score for birthweight
      (1.33 +/- 1.34; p < 0.001) were higher in type 1 diabetes and increased over time
      from 1.22 to 1.47 (p < 0.001). Birthweight was also increased in type 2 diabetes
      (0.94 +/- 1.34; p < 0.001) but did not alter with time. There were 65 perinatal
      deaths in offspring of mothers with type 1 diabetes and 39 to mothers with type 2
      diabetes, representing perinatal mortality rates of 20.1 (95% CI 14.7, 24.3) and
      26.9 (16.7, 32.9) per 1000 births, respectively, and rates 3.1 and 4.2 times,
      respectively, those observed in the non-diabetic population (p < 0.001).
      Stillbirth rates in type 1 and type 2 diabetes were 4.0-fold and 5.1-fold that in
      the non-diabetic population (p < 0.001). Perinatal mortality and stillbirth rates
      showed no significant fall over time despite small falls in the rates for the non
      diabetic population. CONCLUSIONS/INTERPRETATION: Women with diabetes are
      receiving increased intervention in pregnancy (earlier delivery, increased
      Caesarean section rates), but despite this, higher birthweights are being
      recorded. Improvements in rates of stillbirth seen in the general population are
      not being reflected in changes in stillbirth or perinatal mortality in our
      population with diabetes.

PMID- 29322219
TI  - SIRT6-mediated transcriptional suppression of Txnip is critical for pancreatic
      beta cell function and survival in mice.
AB  - AIMS/HYPOTHESIS: Better understanding of how genetic and epigenetic components
      control beta cell differentiation and function is key to the discovery of novel
      therapeutic approaches to prevent beta cell dysfunction and failure in the
      progression of type 2 diabetes. Our goal was to elucidate the role of histone
      deacetylase sirtuin 6 (SIRT6) in beta cell development and homeostasis. METHODS:
      Sirt6 endocrine progenitor cell conditional knockout and beta cell-specific
      knockout mice were generated using the Cre-loxP system. Mice were assayed for
      islet morphology, glucose tolerance, glucose-stimulated insulin secretion and
      susceptibility to streptozotocin. Transcriptional regulatory functions of SIRT6
      in primary islets were evaluated by RNA-Seq analysis. Reverse transcription
      quantitative (RT-q)PCR and immunoblot were used to verify and investigate the
      gene expression changes. Chromatin occupancies of SIRT6, H3K9Ac, H3K56Ac and
      active RNA polymerase II were evaluated by chromatin immunoprecipitation.
      RESULTS: Deletion of Sirt6 in pancreatic endocrine progenitor cells did not
      affect endocrine morphology, beta cell mass or insulin production but did result
      in glucose intolerance and defective glucose-stimulated insulin secretion in
      mice. Conditional deletion of Sirt6 in adult beta cells reproduced the insulin
      secretion defect. Loss of Sirt6 resulted in aberrant upregulation of thioredoxin
      interacting protein (TXNIP) in beta cells. SIRT6 deficiency led to increased
      acetylation of histone H3 lysine residue at 9 (H3K9Ac), acetylation of histone H3
      lysine residue at 56 (H3K56Ac) and active RNA polymerase II at the promoter
      region of Txnip. SIRT6-deficient beta cells exhibited a time-dependent increase
      in H3K9Ac, H3K56Ac and TXNIP levels. Finally, beta cell-specific SIRT6-deficient
      mice showed increased sensitivity to streptozotocin. CONCLUSIONS/INTERPRETATION:
      Our results reveal that SIRT6 suppresses Txnip expression in beta cells via
      deacetylation of histone H3 and plays a critical role in maintaining beta cell
      function and viability. DATA AVAILABILITY: Sequence data have been deposited in
      the National Institutes of Health (NIH) Gene Expression Omnibus (GEO) with the
      accession code GSE104161.

PMID- 29322221
TI  - Feasibility of opportunistic osteoporosis screening in routine contrast-enhanced
      multi detector computed tomography (MDCT) using texture analysis.
AB  - : This study investigated the feasibility of opportunistic osteoporosis screening
      in routine contrast-enhanced MDCT exams using texture analysis. The results
      showed an acceptable reproducibility of texture features, and these features
      could discriminate healthy/osteoporotic fracture cohort with an accuracy of 83%.
      INTRODUCTION: This aim of this study is to investigate the feasibility of
      opportunistic osteoporosis screening in routine contrast-enhanced MDCT exams
      using texture analysis. METHODS: We performed texture analysis at the spine in
      routine MDCT exams and investigated the effect of intravenous contrast medium
      (IVCM) (n = 7), slice thickness (n = 7), the long-term reproducibility (n = 9),
      and the ability to differentiate healthy/osteoporotic fracture cohort (n = 9 age
      and gender matched pairs). Eight texture features were extracted using gray level
      co-occurrence matrix (GLCM). The independent sample t test was used to rank the
      features of healthy/fracture cohort and classification was performed using
      support vector machine (SVM). RESULTS: The results revealed significant
      correlations between texture parameters derived from MDCT scans with and without
      IVCM (r up to 0.91) slice thickness of 1 mm versus 2 and 3 mm (r up to 0.96) and
      scan-rescan (r up to 0.59). The performance of the SVM classifier was evaluated
      using 10-fold cross-validation and revealed an average classification accuracy of
      83%. CONCLUSIONS: Opportunistic osteoporosis screening at the spine using
      specific texture parameters (energy, entropy, and homogeneity) and SVM can be
      performed in routine contrast-enhanced MDCT exams.

PMID- 29322222
TI  - Urinary Pentosidine levels negatively associates with trabecular bone scores in
      patients with type 2 diabetes mellitus.
AB  - : Pentosidine levels were higher in diabetic patients with vertebral fractures.
      Trabecular bone scores were negatively associated with pentosidine levels in
      diabetic patients only. Our results provide further evidence that AGEs are
      associated with the pathogenesis of bone fragility in patients with T2DM.
      INTRODUCTION: Type 2 diabetes mellitus (T2DM) is associated with fracture risk.
      Pentosidine, an advanced glycation end product (AGE), is associated with
      prevalent vertebral fractures (VFs) in patients with T2DM. Trabecular bone score
      (TBS) has been proposed as an index of bone microarchitecture associated with
      bone quality. This study evaluated the associations of urine pentosidine and TBS
      in T2DM and non-T2DM groups. METHODS: A total of 112 T2DM patients and 62 non
      T2DM subjects were enrolled. TBS was calculated using TBS insight(r) software
      (version 2.1). Pentosidine levels were measured using high-performance liquid
      chromatography method. We compared the BMD, TBS, and pentosidine levels between
      those with and without VFs with or without adjustment for age and sex. The
      association with TBS, lumbar spine BMD, and pentosidine levels were also
      evaluated in both T2DM and non-T2DM groups. RESULTS: Pentosidine levels were
      significantly higher in T2DM patients with VFs. TBSs were significantly lower in
      patients with T2DM and VFs. In non-diabetic patients, there were no significant
      differences in TBS and pentosidine levels for those with and without VFs after
      adjustment for age and sex. Pentosidine levels were negatively associated with
      TBS only in patients with T2DM. In multivariate stepwise regression analysis,
      pentosidine levels were significantly associated with TBS in patients with T2DM.
      CONCLUSIONS: TBS and pentosidine could be used as a method to assess bone quality
      to identify T2DM patients at risk of VFs. Our results also provide further
      evidence that AGEs are associated with the pathogenesis of bone fragility in
      patients with T2DM.

PMID- 29322224
TI  - [Chronic spontaneous urticaria : A disease of civilization?]

PMID- 29322223
TI  - Is the timed loaded standing test a valid measure of back muscle endurance in
      people with vertebral osteoporosis?
AB  - : Timed loaded standing (TLS) is a suggested measure of back muscle endurance for
      people with vertebral osteoporosis. Surface electromyography revealed back
      muscles work harder and fatigue during TLS. The test end-point and total time
      were associated with back fatigue. The findings help demonstrate the concurrent
      validity of the TLS test. INTRODUCTION: The TLS test is suggested as a measure of
      back muscle endurance for patients with vertebral osteoporosis. However, to date,
      no study has demonstrated that TLS does measure back extensor or erector spinae
      (ES) muscle endurance. We used surface electromyography (sEMG) to investigate the
      performance of the thoracic ES muscles during TLS. METHODS: Thirty-six people
      with vertebral osteoporosis with a mean age of 71.6 (range 45-86) years
      participated. sEMG recordings were made of the ES at T3 and T12 bilaterally
      during quiet standing (QS) and TLS. The relative (%) change in sEMG amplitude
      between conditions was compared. Fatigue was evaluated by analysing the change in
      median frequency (MF) of the sEMG signal during TLS, and the correlation between
      maximal TLS time and rate of MF decline was examined. RESULTS: Activity in the ES
      increased significantly during TLS at all electrode locations. During TLS, the MF
      declined at a mean rate of -24.2% per minute (95% C.I. -26.5 to -21.9%). The MF
      slope and test time were strongly correlated (r2 = 0.71), and at test end, the
      final MF dropped to an average 89% (95% C.I. 85 to 93%) of initial MF. Twenty
      eight participants (78%) reported fatigue was the main reason for stopping, and
      for eight (22%), it was pain. CONCLUSIONS: This study demonstrates that TLS
      challenges the ES muscles in the thoracic region and results in ES fatigue.
      Endurance time and the point at which the TLS test ends are strongly related to
      ES fatigue.

PMID- 29322227
TI  - ?

PMID- 29322225
TI  - [Surgical treatment options for hidradenitis suppurativa/acne inversa].
AB  - Hidradenitis suppurativa/acne inversa (HS/AI) is a chronic inflammatory skin
      disease. Therapy consists of conservative and surgical treatment options. In
      Hurley stages II and III, surgical intervention is regarded as the method of
      choice for areas with irreversible tissue destruction. Resection techniques with
      different grades of invasiveness are described in the literature. Nevertheless,
      there is no generally accepted concept regarding resection and reconstruction
      techniques or specific postoperative care. Due to lack of definitions of
      recurrence after surgery and poor study quality, recurrence rates are difficult
      to determine.

PMID- 29322228
TI  - [Necrotizing fasciitis of the hand and forearm : Acute surgical treatment and
      defect reconstruction with MatriDerm(r) and split-thickness skin graft].
AB  - This case report describes a 55-year-old male patient with type II necrotizing
      fasciitis (NF) of the hand and forearm. The rapid progression of the tissue
      infection could be successfully stopped with radical surgical debridement and
      antibiotic therapy. For the reconstruction of the extensive loss of soft tissue a
      combination of split-thickness skin graft (STSG) and the synthetic dermal
      substitute MatriDerm(r) was used. In cases of NF, MatriDerm(r) and STSG provide a
      rapidly available and simple alternative to other reconstruction techniques.

PMID- 29322226
TI  - Nebivolol, a beta-blocker abrogates streptozotocin-induced behavioral,
      biochemical, and neurophysiological deficit by attenuating oxidative-nitrosative
      stress: a possible target for the prevention of diabetic neuropathy.
AB  - Metabolic abnormalities including hyperglycemia, hyperlipidemia, and oxidative
      nitrosative stress are involved in the progression of diabetic neuropathy. In the
      present study, we targeted oxidative-nitrosative stress using nebivolol, a beta1
      receptor antagonist with vasodilator and antioxidant property, to evaluate its
      neuroprotective effect in streptozotocin-induced diabetic neuropathy in rats.
      Diabetic neuropathy develops within 4-6 weeks after administration of
      streptozotocin (55 mg/kg, i.p.). Therefore, after confirmation of diabetes,
      subtherapeutic doses of nebivolol (1 and 2 mg/kg, p.o./day) were given to
      diabetic rats for 8 weeks. Nebivolol treatment significantly improved thermal
      hyperalgesia, grip strength, and motor coordination. Nebivolol also reduced
      levels of malondialdehyde, tumor necrosis factor-alpha, and nitrite in diabetes.
      Moreover, nebivolol increased the levels of superoxide dismutase and catalase in
      sciatic nerve homogenate of diabetic rats. Further, nebivolol exerted positive
      effects on lipid profile, sciatic nerve's morphological changes and nerve
      conduction velocity in diabetic rats. Results of the present study suggest the
      neuroprotective effect of nebivolol through its antioxidant, nitric oxide
      potentiating, and antihyperlipidemic activity.

PMID- 29322229
TI  - Bioanalytical verification of V-type nerve agent exposure: simultaneous detection
      of phosphonylated tyrosines and cysteine-containing disulfide-adducts derived
      from human albumin.
AB  - Nerve agents still represent a serious threat to civilian and military personnel
      as demonstrated by the violent conflict in the Middle East. For verification of
      poisoning, covalent adducts with endogenous proteins (e.g., human serum albumin,
      HSA) are valuable long-term biomarkers. Accordingly, we developed a microbore
      liquid chromatography-electrospray ionization mass spectrometry/high-resolution
      mass spectrometry (MULC-ESI MS/HR MS) method for simultaneous detection of HSA
      adducts with the V-type nerve agents VX, Chinese VX (CVX), and Russian VX (RVX).
      Following Pronase-catalyzed proteolysis, novel disulfide-adducts were detected in
      addition to phosphonylated tyrosine residues. Dipeptide disulfide-adducts were
      formed between the thiol-containing leaving group of the V-type nerve agents (2
      (diisopropylamino)ethanethiol, DPAET, for VX and 2-(diethylamino)ethanethiol,
      DEAET, for CVX and RVX) and the free thiol group of Cys34 in HSA (DPAET-CysPro,
      DEAET-CysPro). We also identified tripeptide disulfide-adducts containing Cys448
      (MetProCys-DPAET, MetProCys-DEAET) and to a lesser extent Cys514 (AspIleCys
      DPAET, AspIleCys-DEAET). Synthetic tripeptide references were used for
      confirmation of the postulated structures by MULC-ESI MS/HR MS. Lower limits of
      detection were determined in human plasma, being nearly identical for the three V
      type nerve agents, and corresponded to 1-6 MUM nerve agent for tyrosine-adducts,
      1-3 MUM nerve agent for CysPro-adducts, and 6 MUM nerve agent for MetProCys
      adducts, thus covering concentrations of toxicological relevance.
      Characterization of proteolysis kinetics revealed stable plateaus for all adducts
      being reached between 60 and 90 min at 37  degrees C. Adduct formation kinetics
      were characterized by simultaneously monitoring the V-type nerve agent, its
      leaving group, and the corresponding disulfide dimer. Furthermore, adduct
      formation patterns were investigated as a function of the molar ratio of HSA to V
      type nerve agent. Graphical abstract Modification of human serum albumin (HSA) by
      V-type nerve agents Chinese VX (CVX) and RussianVX (RVX). Various tyrosine
      residues (Tyr???)n (e.g. most reactive Tyr411) were phosphonylated and disulfide
      adducts were formed between the thiol-containing leaving group 2
      (diethylamino)ethanethiol (DEAET) and at least three cysteine residues (Cys34,
      Cys448 and Cys514). Pronase-mediated proteolysis produced low-molecular cleavage
      products including phosphonylated tyrosines, dipeptide (Cys34Pro) and tripeptide
      (MetProCys448, AspIleCys514) disulfide-adducts that were detected by microbore
      liquid chromatography-electrospray ionization mass spectrometry/high-resolution
      mass spectrometry (MULC-ESI MS/HR MS).

PMID- 29322230
TI  - Migration of Paraburkholderia terrae BS001 Along Old Fungal Hyphae in Soil at
      Various pH Levels.
AB  - The movement of bacterial cells along with fungal hyphae in soil (the mycosphere)
      has been reported in several previous studies. However, how local soil conditions
      affect bacterial migration direction in the mycosphere has not been extensively
      studied. Here, we investigated the influence of two soil parameters, pH and soil
      moisture content, on the migration, and survival, of Paraburkholderia terrae
      BS001 in the mycosphere of Lyophyllum sp. strain Karsten in microcosms containing
      a loamy sand soil. The data showed that bacterial movement along the hyphal
      networks took place in both the "forward" and the "backward" directions. Low soil
      pH strongly restricted bacterial survival, as well as dispersal in both
      directions, in the mycosphere. The backward movement was weakly correlated with
      the amount of fungal tissue formed in the old mycelial network. The initial soil
      moisture content, set at 12 versus 17% (corresponding to 42 and 60% of the soil
      water holding capacity), also significantly affected the bacterial dispersal
      along the fungal hyphae. Overall, the presence of fungal hyphae was found to
      increase the soil pH (under conditions of acidity), which possibly exerted
      protective effects on the bacterial cells. Finally, we provide a refined model
      that describes the bacterial migration patterns with fungal hyphae based on the
      new findings in this study.

PMID- 29322231
TI  - The effect of food on the pharmacokinetics of niraparib, a poly(ADP-ribose)
      polymerase (PARP) inhibitor, in patients with recurrent ovarian cancer.
AB  - PURPOSE: Niraparib is a highly selective inhibitor of PARP-1 and PARP-2 approved
      in the United States for maintenance treatment of adult patients with recurrent
      ovarian cancer in complete or partial response to platinum-based chemotherapy. In
      this open-label crossover study, we evaluated the effects of food on niraparib
      pharmacokinetics (PK) and safety. METHODS: Patients received a single 300-mg dose
      of niraparib either after a high-fat meal or under fasting conditions. After a 7
      day PK assessment, all patients received a second 300-mg dose of niraparib under
      the opposite condition, followed by 7-day PK assessment. Blood samples for PK
      analyses were collected at baseline (on days 1 and 8) and up to 168 h post-dose.
      Bioequivalence between conditions was defined by the 90% confidence intervals
      (CIs) for area under the plasma concentration-time curve (AUC) from 0 to last
      measurable concentration (AUC0-last) and from 0 to infinity (AUC0-infinity) being
      within the 80-125% range. RESULTS: The high-fat meal/fasting ratios of geometric
      least-squares means for AUC0-last and AUC0-infinity were 106.8 (90% CI 97.8
      116.6) and 110.1 (90% CI 99.7-121.6), respectively, indicating bioequivalence
      between conditions. Mean half-life, maximum plasma concentration (Cmax), and time
      to Cmax after the high-fat meal were similar to, 27% smaller than, and 128%
      greater than after fasting, respectively. Adverse events were similar between
      conditions. CONCLUSIONS: A high-fat meal did not impact the PK profile of
      niraparib, indicating that niraparib can be taken with or without food. Niraparib
      was safe and well-tolerated.

PMID- 29322232
TI  - Mechanical Thrombectomy Using the new SolitaireTM Platinum Stent-retriever :
      Reperfusion Results, Complication Rates and Early Neurological Outcome.
AB  - BACKGROUND AND PURPOSE: The application of radiopaque markers to the SolitaireTM
      stent-retriever for better visibility during mechanical thrombectomy (MT) has the
      potential to alter the well-known characteristics of the device; however, it is
      uncertain whether this adjustment influences efficacy or safety of the enhanced
      stent-retriever. METHODS: Retrospective analysis of stroke databases of three
      comprehensive stroke centers. Our investigation was focused on technical and
      angiographic parameters, including procedure times, reperfusion results
      (thrombolysis in cerebral infarction, TICI), periprocedural complications and
      favorable early neurological recovery at discharge (modified Rankin scale <=2 or
      National Institutes of Health Stroke Scale, NIHSS = 0 or ?NIHSS >= 10), from
      consecutive patients with acute anterior circulation ischemic stroke treated with
      a SolitaireTM Platinum stent-retriever between October 2016 and March 2017.
      RESULTS: A total of 75 patients (male: n = 27, 36%, age in years: mean (SD): 75
      (+/-12), median baseline NIHSS: 17 (interquartile range IQR: 11-21), n = 41,
      54.7% received additional i. v. thrombolytics) were treated with a median number
      of 2 device passes (range: 1-5). The median time from groin puncture to final
      TICI was 56 min (IQR: 41-79). In 69 patients (92%) TICI 2b-3 was achieved. Early
      neurological recovery was seen in 47 (62.7%) patients. The following
      periprocedural complications occurred: vasospasms (n = 7, 9.3%), emboli into a
      new territory (n = 4, 5.3%), symptomatic intracranial hemorrhage (n = 3, 4%),
      difficulties during device delivery/deployment (n = 1, 1.3%). CONCLUSION: The
      usage of the SolitaireTM Platinum stent-retriever for MT in acute ischemic stroke
      patients was highly effective and was not accompanied by an increased
      periprocedural complication rate.

PMID- 29322233
TI  - High Isotropic Resolution T2 Mapping of the Lumbosacral Plexus with T2-Prepared
      3D Turbo Spin Echo.
AB  - PURPOSE: Isotropic high-resolution three-dimensional (3D) magnetic resonance
      neurography (MRN) is increasingly used to depict even small and highly oblique
      nerves of the lumbosacral plexus (LSP). The present study introduces a T2 mapping
      sequence (T2-prepared 3D turbo spin echo) that is B1-insensitive and enables
      quantitative assessment of LSP nerves. METHODS: In this study 15 healthy subjects
      (mean age 28.5 +/- 3.8 years) underwent 3 T MRN of the LSP area three times. The
      T2 values were calculated offline on a voxel-by-voxel basis and measured at three
      segments (preganglionic, ganglionic, postganglionic) of three LSP nerves (S1, L5,
      L4) by two independent investigators (experienced and novice). Normative data for
      the different nerves were extracted and intraclass correlation coefficients
      (ICCs) were calculated to assess reproducibility and interobserver reliability of
      T2 measurements. RESULTS: The T2 mapping showed excellent reproducibility with
      ICCs ranging between 0.99 (S1 preganglionic) and 0.89 (L5 postganglionic).
      Interobserver reliability was less robust with ICCs ranging between 0.78 (S1
      preganglionic) and 0.44 (L5 postganglionic) for S1 and L5. A mean T2 value of
      74.6 +/- 4.7 ms was registered for preganglionic segments, 84.7 +/- 4.1 ms for
      ganglionic and 65.4 +/- 2.5 ms for postganglionic segments, respectively. There
      was a statistically significant variation of T2 values across the nerve
      (preganglionic vs ganglionic vs postganglionic) for S1, L5, and L4. CONCLUSION:
      Our approach enables isotropic high-resolution and B1-insensitive T2 mapping of
      LSP nerves with excellent reproducibility. It might reflect a robust and
      clinically useful method for future diagnostics of LSP pathologies.

PMID- 29322234
TI  - [Efficacy of a ketogenic diet in urological cancers patients : A systematic
      review].
AB  - BACKGROUND: Beside the classical anticancer treatment tumor patients try to find
      proactive alternative therapies to fight their disease. Lifestyle changes such as
      introducing a ketogenic diet is one of the most popular among them. The German
      Association of Urological Oncology (AUO, Arbeitsgemeinschaft Urologische
      Onkologie) presents a systematic review investigating the evidence of ketogenic
      diet in cancer patients. MATERIALS AND METHODS: A systematic literature research
      was conducted in the databases Medline, Livivo, and the Cochrane Library. Only
      clinical studies of tumor patients receiving chemotherapy while on a ketogenic
      diet were included. The assessment of the results was performed according to the
      predefined primary endpoints overall survival and progression-free survival and
      secondary endpoints quality of life and reduction of adverse effects induced by
      cytostatics. RESULTS: Nine studies met the inclusion criteria: eight prospective
      and one retrospective study case series respectively cohort-studies, with a total
      of 107 patients. Currently there is no evidence of a therapeutic effect of a
      ketogenic diet in patients with malignant tumors regarding the clinical outcome
      or quality of life. CONCLUSION: Based on the current data, a ketogenic diet can
      not be recommended to cancer patients because prospective, randomized trials are
      missing.

PMID- 29322236
TI  - [Urosepsis].
AB  - Urosepsis is defined as a severe disease due to organ failure caused by a urinary
      tract infection. An empirical antibiotic therapy should be instigated within the
      first hour after diagnosis. Urine cultures and blood cultures should be performed
      before antibiotic treatment. Further diagnostics should be carried out at an
      early stage to enable an interventional focus control in the case of urinary
      tract obstruction or abscess formation, if necessary. Gram-negative pathogens are
      most frequently isolated. Extended spectrum beta-lactamase (ESBL) forming
      bacteria as a cause of urosepsis are increasing. Carbapenemase-forming
      Enterobacteriaceae, on the other hand, are still rare. The empirical treatment
      consists of a broad spectrum beta-lactam antibiotic. While
      piperacillin/tazobactam, carbapenems and the new cephalosporin/beta-lactamase
      inhibitor (BLI) combinations are given as monotherapy, cephalosporins should be
      combined with aminoglycosides (preferred) or fluoroquinolones. If a combination
      therapy is given, it should be de-escalated to a monotherapy after 48-72 h.

PMID- 29322237
TI  - Genome-wide association study of cold tolerance of Chinese indica rice varieties
      at the bud burst stage.
AB  - KEY MESSAGE: A region containing three genes on chromosome 1 of indica rice was
      associated with cold tolerance at the bud burst stage; these results may be
      useful for breeding cold-tolerant lines. Low temperature at the bud burst stage
      is one of the major abiotic stresses limiting rice growth, especially in regions
      where rice seeds are sown directly. In this study, we investigated cold tolerance
      of rice at the bud burst stage and conducted a genome-wide association study
      (GWAS) based on the 5K rice array of 249 indica rice varieties widely distributed
      in China. We improved the method to assess cold tolerance at the bud burst stage
      in indica rice, and used severity of damage (SD) and seed survival rate (SR) as
      the cold-tolerant indices. Population structure analysis demonstrated that the
      Chinese indica panel was divided into three subgroups. In total, 47 significant
      single-nucleotide polymorphism (SNP) loci associated with SD and SR, were
      detected by association mapping based on mixed linear model. Because some loci
      overlapped between SD and SR, the loci contained 13 genome intervals and most of
      them have been reported previously. A major QTL for cold tolerance on chromosome
      1 at the position of 31.6 Mb, explaining 13.2% of phenotypic variation, was
      selected for further analysis. Through LD decay, GO enrichment, RNA-seq data, and
      gene expression pattern analyses, we identified three genes (LOC_Os01g55510,
      LOC_Os01g55350 and LOC_Os01g55560) that were differentially expressed between
      cold-tolerant and cold-sensitive varieties, suggesting they may be candidate
      genes for cold tolerance. Together, our results provide a new method to assess
      cold tolerance in indica rice, and establish the foundation for isolating genes
      related to cold tolerance that could be used in rice breeding.

PMID- 29322235
TI  - [Interrater reliability and clinical impact of the Post-Ureteroscopic Lesion
      Scale (PULS) grading system for ureteral lesions after ureteroscopy : Results of
      the German prospective multicenter BUSTER project].
AB  - BACKGROUND: The Post-ureteroscopic Lesion Scale (PULS) was designed as a
      standardized classification system for ureteral lesions after uretero(reno)scopy
      (URS). This study evaluates its routine use and a possible clinical impact based
      on a representative patient cohort. MATERIALS AND METHODS: Data of 307 patients
      in 14 German centers within the BUSTER project were used to test 3 hypotheses
      (H): PULS score shows a high interrater reliability (IRR) after independent
      assessment by urologic surgeon and assistance personnel (H1); PULS score is
      correlated with the frequency of postoperative complications during hospital stay
      (H2); post-URS stenting of the ureter is associated with higher PULS scores (H3).
      RESULTS: Median age of patients was 54.4 years (interquartile range [IQR] 44.4
      65.8; 65.5% male). Median diameter of index stones was 6 mm (IQR 4-8) with 117
      (38.4%) pyelo-caliceal and 188 (61.6%) ureteral stones. Overall, 70 and 82.4% of
      patients had pre-stenting and post-URS stenting, respectively. Stone-free status
      was achieved in 68.7% after one URS procedure with a complication rate of 10.8%
      (mostly grade 1-2 according to Clavien-Dindo). PULS scores 0, 1, 2 and 3 were
      assessed in 40%, 52.1%, 6.9% and 1% of patients, respectively, when estimated by
      urologic surgeons. PULS score showed a high IRR between the urologic surgeon and
      assistance personnel (kappa = 0.883, p < 0.001), but was not significantly
      correlated with complications (rho = 0.09, p = 0.881). In contrast, a significant
      positive correlation was found between PULS score and post-URS stenting (rho =
      0.287, p < 0.001). A PULS score of 1 multiplied the likelihood of post-URS
      stenting by 3.24 (95% confidence interval 1.43-7.34; p = 0.005) as opposed to
      PULS score 0. CONCLUSIONS: Removal of upper urinary tract stones using URS is
      safe and efficacious. Real-world data provided by this study confirm a high IRR
      of the PULS score and its clinical impact on the indication for post-URS
      stenting. A future prospective randomized trial should evaluate a possible
      standardization of post-URS stenting based on PULS score assessment.

PMID- 29322238
TI  - Development of inhibitory synaptic inputs on layer 2/3 pyramidal neurons in the
      rat medial prefrontal cortex.
AB  - Inhibitory control of pyramidal neurons plays a major role in governing the
      excitability in the brain. While spatial mapping of inhibitory inputs onto
      pyramidal neurons would provide important structural data on neuronal signaling,
      studying their distribution at the single cell level is difficult due to the lack
      of easily identifiable anatomical proxies. Here, we describe an approach where in
      utero electroporation of a plasmid encoding for fluorescently tagged gephyrin
      into the precursors of pyramidal cells along with ionotophoretic injection of
      Lucifer Yellow can reliably and specifically detect GABAergic synapses on the
      dendritic arbour of single pyramidal neurons. Using this technique and focusing
      on the basal dendritic arbour of layer 2/3 pyramidal cells of the medial
      prefrontal cortex, we demonstrate an intense development of GABAergic inputs onto
      these cells between postnatal days 10 and 20. While the spatial distribution of
      gephyrin clusters was not affected by the distance from the cell body at
      postnatal day 10, we found that distal dendritic segments appeared to have a
      higher gephyrin density at later developmental stages. We also show a transient
      increase around postnatal day 20 in the percentage of spines that are carrying a
      gephyrin cluster, indicative of innervation by a GABAergic terminal. Since the
      precise spatial arrangement of synaptic inputs is an important determinant of
      neuronal responses, we believe that the method described in this work may allow a
      better understanding of how inhibition settles together with excitation, and
      serve as basics for further modelling studies focusing on the geometry of
      dendritic inhibition during development.

PMID- 29322239
TI  - The lateralized arcuate fasciculus in developmental pitch disorders among
      mandarin amusics: left for speech and right for music.
AB  - The arcuate fasciculus (AF) is a neural fiber tract that is critical to speech
      and music development. Although the predominant role of the left AF in speech
      development is relatively clear, how the AF engages in music development is not
      understood. Congenital amusia is a special neurodevelopmental condition, which
      not only affects musical pitch but also speech tone processing. Using diffusion
      tensor tractography, we aimed at understanding the role of AF in music and speech
      processing by examining the neural connectivity characteristics of the bilateral
      AF among thirty Mandarin amusics. Compared to age- and intelligence quotient (IQ)
      matched controls, amusics demonstrated increased connectivity as reflected by the
      increased fractional anisotropy in the right posterior AF but decreased
      connectivity as reflected by the decreased volume in the right anterior AF.
      Moreover, greater fractional anisotropy in the left direct AF was correlated with
      worse performance in speech tone perception among amusics. This study is the
      first to examine the neural connectivity of AF in the neurodevelopmental
      condition of amusia as a result of disrupted music pitch and speech tone
      processing. We found abnormal white matter structural connectivity in the right
      AF for the amusic individuals. Moreover, we demonstrated that the white matter
      microstructural properties of the left direct AF is modulated by lexical tone
      deficits among the amusic individuals. These data support the notion of
      distinctive pitch processing systems between music and speech.

PMID- 29322241
TI  - Halorubrum depositum sp. nov., a Novel Halophilic Archaeon Isolated from a Salt
      Deposit.
AB  - A non-motile, pleomorphic rod-shaped or oval, red-pigmented (nearly scarlet),
      extremely halophilic archaeon, strain Y78T, was isolated from a salt deposit of
      Yunnan salt mine, China. Analysis of the 16S rRNA gene sequence showed that it
      was phylogenetically related to species of the genus Halorubrum, with a close
      relationship to Halorubrum rutilum YJ-18-S1T (98.6%), Halorubrum yunnanense Q85T
      (98.3%), and Halorubrum lipolyticum 9-3T (98.1%). The temperature, NaCl, and pH
      ranges for growth were 25-50  degrees C, 12-30% (w/v), and 6.5-9.0, respectively.
      Mg2+ was required for growth. The polar lipids of strain Y78T were
      phosphatidylglycerol, phosphatidylglycerol phosphate methyl ester,
      phosphatidylglycerol sulfate, and a sulfated diglycosyl diether. The DNA G+C
      content was 66.6 mol%. DNA-DNA hybridization values between strain Y78T and two
      closely related species of the genus Halorubrum were far below 70%. Based on the
      data presented in this study, strain Y78T represents a novel species for which
      the name Halorubrum depositum sp. nov. is proposed; the type strain is Y78T (=
      CGMCC 1.15456T = JCM 31272T).

PMID- 29322242
TI  - Utility of fosfomycin as antibacterial prophylaxis in patients with hematologic
      malignancies.
AB  - PURPOSE: Prolonged and profound neutropenia is common among hematology and
      hematopoietic stem cell transplant (HSCT) patients as a result of chemotherapy.
      The National Comprehensive Cancer Network (NCCN) and Infectious Diseases Society
      of America (IDSA) currently recommend antibacterial prophylaxis in patients who
      are deemed at intermediate or high risk for infection. Specifically,
      fluoroquinolone prophylaxis should be considered for high-risk neutropenic
      patients. However, with prolonged and frequent exposure to fluoroquinolones,
      these high-risk patients may develop resistance to these agents. Patients may
      also have allergies or other contraindications which prohibit the use of
      fluoroquinolones for antibacterial prophylaxis. Unfortunately, there is no
      standard recommendation for alternative antimicrobial therapy in this patient
      population, as well as there is a lack of data to support the use of potential
      alternative agents. METHODS: Currently, Yale-New Haven Hospital utilizes
      fosfomycin for antibacterial prophylaxis in patients who are not eligible for
      fluoroquinolone therapy. The primary objective of this study was to assess the
      incidence of breakthrough infections in this population receiving fosfomycin.
      Secondary objectives included organisms identified, types of breakthrough
      infections, resistance patterns, and time from initiation to onset of fever.
      RESULTS: Of the 42 patients who received fosfomycin, 25 patients with 42
      admissions met inclusion criteria. A total of 8 (19%) breakthrough infections
      occurred during the 42 admissions. Organisms included Klebsiella spp. (5),
      Streptococcus mitis/viridans (2), Pseudomonas aeruginosa (1), and coagulase
      negative staphylococcus (1). Infections included the following: bacteremia (7),
      cellulitis (1), and urine (1). CONCLUSION: Given the low rate of breakthrough
      infections, fosfomycin may be a potential alternative option for antibacterial
      prophylaxis.

PMID- 29322240
TI  - Ki-67: more than a proliferation marker.
AB  - Ki-67 protein has been widely used as a proliferation marker for human tumor
      cells for decades. In recent studies, multiple molecular functions of this large
      protein have become better understood. Ki-67 has roles in both interphase and
      mitotic cells, and its cellular distribution dramatically changes during cell
      cycle progression. These localizations correlate with distinct functions. For
      example, during interphase, Ki-67 is required for normal cellular distribution of
      heterochromatin antigens and for the nucleolar association of heterochromatin.
      During mitosis, Ki-67 is essential for formation of the perichromosomal layer
      (PCL), a ribonucleoprotein sheath coating the condensed chromosomes. In this
      structure, Ki-67 acts to prevent aggregation of mitotic chromosomes. Here, we
      present an overview of functional roles of Ki-67 across the cell cycle and also
      describe recent experiments that clarify its role in regulating cell cycle
      progression in human cells.

PMID- 29322244
TI  - Metacontrol and body ownership: divergent thinking increases the virtual hand
      illusion.
AB  - The virtual hand illusion (VHI) paradigm demonstrates that people tend to
      perceive agency and bodily ownership for a virtual hand that moves in synchrony
      with their own movements. Given that this kind of effect can be taken to reflect
      self-other integration (i.e., the integration of some external, novel event into
      the representation of oneself), and given that self-other integration has been
      previously shown to be affected by metacontrol states (biases of information
      processing towards persistence/selectivity or flexibility/integration), we tested
      whether the VHI varies in size depending on the metacontrol bias. Persistence and
      flexibility biases were induced by having participants carry out a convergent
      thinking (Remote Associates) task or divergent-thinking (Alternate Uses) task,
      respectively, while experiencing a virtual hand moving synchronously or
      asynchronously with their real hand. Synchrony-induced agency and ownership
      effects were more pronounced in the context of divergent thinking than in the
      context of convergent thinking, suggesting that a metacontrol bias towards
      flexibility promotes self-other integration.

PMID- 29322243
TI  - Humanistic burden of disease for patients with advanced melanoma in Canada.
AB  - BACKGROUND: Metastatic melanoma is a highly aggressive cancer, often striking in
      the prime of life. This study provides new information directly from advanced
      melanoma (stage III and IV) patients on how their disease impacts their health
      related quality of life (HRQL). METHODS: Twenty-nine in-depth, qualitative
      interviews were conducted with adult patients with advanced melanoma in Canada. A
      semi-structured interview guide was used. Interviews were transcribed verbatim
      and key concepts were identified using a grounded theory analytic approach.
      RESULTS: Many patients' journeys began with the startling diagnosis of an
      invasive disease and a vastly shortened life expectancy. By the time they reached
      an advanced stage of melanoma, these patients' overall functioning and quality of
      life had been greatly diminished by this quickly progressing cancer. The impact
      was described in terms of physical pain and disability, emotional distress,
      diminished interactions with friends and family, and burden on caregivers.
      CONCLUSION: Our findings provide evidence of signs, symptoms, and functional
      impacts of advanced melanoma. Signs and symptoms reported (physical, mental, and
      social) confirm and expand on those reported in the existing clinical literature.
      Primary care physicians should be better trained to identify melanomas early.
      Oncology care teams can improve on their current approaches for helping patients
      navigate treatment options, with information about ancillary services to mitigate
      disease impacts on HRQL, such as mental health and social supports, as well as
      employment or financial support services.

PMID- 29322245
TI  - Interactions between incentive valence and action information in a cued approach
      avoidance task.
AB  - Environmental stimuli can provoke specific response tendencies depending on their
      incentive valence. While some studies report positive-approach and negative
      avoidance biases, others find no such mappings. To further illuminate the
      relationship between incentive valence and action requirement, we combined a cued
      monetary incentive paradigm with an approach/avoidance joystick task. Incentive
      type was manipulated between groups: The reward group won money, while the
      punishment group avoided losing money for correct and fast responses to targets
      following incentive cues. Depending on their orientations, targets had to be
      'approached' or 'avoided'. Importantly, incentive valence (signaled by cue color)
      was orthogonal to action requirement (target orientation). Moreover, targets
      could carry valence-associated information or not (target color), which was,
      however, task-irrelevant. First, we observed that both valence cues
      (reward/punishment) improved performance compared to neutral cues, independent of
      the required action (approach/avoid), suggesting that advance valence cues do not
      necessarily produce specific action biases. Second, task-irrelevant valence
      associations with targets promoted action biases, with valence-associated targets
      facilitating approach and impairing avoid responses. Importantly, this approach
      bias for valence-associated targets was observed in both groups and hence
      occurred independently of absolute valence ('unsigned'). This rather unexpected
      finding might be related to the absence of a direct contrast between positive
      valence and negative valence within groups and the common goal to respond fast
      and accurately in all incentive trials. Together, our results seem to challenge
      the notion that monetary incentives trigger 'hard-wired' valence-action biases in
      that specific design choices seem to modulate the presence and/or direction of
      valence-action biases.

PMID- 29322246
TI  - De novo variants in SETD1B are associated with intellectual disability, epilepsy
      and autism.
AB  - SETD1B (SET domain containing 1B) is a component of SET1 histone
      methyltransferase complex, which mediates the methylation of histone H3 on lysine
      4 (H3K4). Here, we describe two unrelated individuals with de novo variants in
      SETD1B identified by trio-based whole exome sequencing: c.5524C>T, p.(Arg1842Trp)
      and c.5575C>T, p.(Arg1859Cy). The two missense variants occurred at
      evolutionarily conserved amino acids and are located within the SET domain, which
      plays a pivotal role in catalyzing histone methylation. Previous studies have
      suggested that de novo microdeletions in the 12q24.3 region encompassing SETD1B
      were associated with developmental delays, intellectual disabilities,
      autism/autistic behavior, large stature and craniofacial anomalies. Comparative
      mapping of 12q24.3 deletions refined the candidate locus, indicating KDM2B and
      SETD1B to be the most plausible candidate genes for the pathogenicity of 12q24.3
      deletion syndrome. Our cases showed epilepsy, developmental delay, intellectual
      disabilities, autistic behavior and craniofacial dysmorphic features, which are
      consistent with those of individuals with de novo 12q24.31 deletions. Therefore,
      our study suggests that SETD1B aberration is likely to be the core defect in
      12q24.3 deletion syndrome.

PMID- 29322247
TI  - Comparison of the neuroinflammatory responses to selective retina therapy and
      continuous-wave laser photocoagulation in mouse eyes.
AB  - PURPOSE: This study investigated microglia and inflammatory cell responses after
      selective retina therapy (SRT) with microsecond-pulsed laser in comparison to
      continuous-wave laser photocoagulation (cwPC). METHODS: Healthy C57BL/6 J mice
      were treated with either a train of short pulses (SRT; 527-nm, Q-switched, 1.7
      MUs pulse) or a conventional thermal continuous-wave (532-nm, 100-ms pulse
      duration) laser. The mice were sacrificed and their eyes were enucleated 1, 3, 7,
      and 14 days after both laser treatments. Pattern of cell death on retinal section
      was evaluated by TUNEL assay, and the distribution of activated inflammatory
      cells and glial cells were observed under immunohistochemistry. Consecutive
      changes for the expression of cytokines such as IL-1beta, TNF-alpha, and TGF-beta
      were also examined using immunohistochemistry, and compared among each period
      after quantification by Western blotting. RESULTS: The numbers of TUNEL-positive
      cells in the retinal pigment epithelium (RPE) layer did not differ in SRT and
      cwPC lesions, but TUNEL-positive cells in neural retinas were significantly less
      on SRT. Vague glial cell activation was observed in SRT-treated lesions. The
      population of inflammatory cells was also significantly decreased after SRT, and
      the cells were located in the RPE layer and subretinal space. Proinflammatory
      cytokines, including IL-1beta and TNF-alpha, showed significantly lower levels
      after SRT; conversely, the level of TGF-beta was similar to the cwPC-treated
      lesion. CONCLUSIONS: SRT resulted in selective RPE damage without collateral
      thermal injury to the neural retina, and apparently produced negligible glial
      activation. In addition, SRT showed a markedly less inflammatory response than
      cwPC, which may have important therapeutic implications for several macular
      diseases.

PMID- 29322248
TI  - A reversible liquid drop aggregation controls glucose response in yeast.
AB  - Glucose is the preferred carbon of the yeast Saccharomyces cerevisiae. Depletion
      of glucose activates SNF1 (yeast AMP-activated protein kinase-AMPK), allowing
      cells to switch from fermentation to respiration. We have recently characterized
      the mechanism by which SNF1 activity is regulated by the Std1 protein, and its
      regulator Sip5. The hitherto uncharacterized protein kinase Vhs1 phosphorylates
      Sip5 in response to glucose availability, disengaging it from Std1 and promoting
      the sequestering of the SNF1 activator out of the nucleus into cytoplasmic
      puncta. These aggregates, which have the properties of liquid drops, and not of
      amyloids, reside in the nucleus-vacuole junction. The process is reversible, and
      Std1 puncta dissolve when glucose becomes scarce again. This reversible process
      requires protein chaperones, similar to the aggregation of toxic or misfolded
      proteins such as those associated with Huntington's Chorea, Alzheimer's and CJD
      diseases. Our results thus reveal a regulated, non-pathological, physiological
      role of protein aggregation that controls a major metabolic cellular pathway.

PMID- 29322249
TI  - MiR-375 inhibits the hepatocyte growth factor-elicited migration of mesenchymal
      stem cells by downregulating Akt signaling.
AB  - The migration of mesenchymal stem cells (MSCs) is critical for their use in cell
      based therapies. Accumulating evidence suggests that microRNAs are important
      regulators of MSC migration. Here, we report that the expression of miR-375 was
      downregulated in MSCs treated with hepatocyte growth factor (HGF), which strongly
      stimulates the migration of these cells. Overexpression of miR-375 decreased the
      transfilter migration and the migration velocity of MSCs triggered by HGF. In our
      efforts to determine the mechanism by which miR-375 affects MSC migration, we
      found that miR-375 significantly inhibited the activation of Akt by
      downregulating its phosphorylation at T308 and S473, but had no effect on the
      activity of mitogen-activated protein kinases. Further, we showed that
      3'phosphoinositide-dependent protein kinase-1 (PDK1), an upstream kinase
      necessary for full activation of Akt, was negatively regulated by miR-375 at the
      protein level. Moreover, miR-375 suppressed the phosphorylation of focal adhesion
      kinase (FAK) and paxillin, two important regulators of focal adhesion (FA)
      assembly and turnover, and decreased the number of FAs at cell periphery. Taken
      together, our results demonstrate that miR-375 inhibits HGF-elicited migration of
      MSCs through downregulating the expression of PDK1 and suppressing the activation
      of Akt, as well as influencing the tyrosine phosphorylation of FAK and paxillin
      and FA periphery distribution.

PMID- 29322251
TI  - Rhinoplasty: lessons from "errors" : From anatomy and experience to the concept
      of sequential primary rhinoplasty.
AB  - BACKGROUND: Reshaping the nose can be achieved following 3 main concepts:
      preservation and reshaping of normal anatomy, resection of nasal deformities,
      reconstruction of nasal framework. Time, experience and nasal anatomic knowledge
      are keys to understand nasal biomechanics. OBJECTIVES: To describe how experience
      and morphodynamic anatomy lead to a new concept of sequential primary
      rhinoplasty, resulting in reducing revision rhinoplasties. METHODS: Through 36
      years' experience in different rhinoplasty procedures, 25 years in personal
      anatomic studies of the nose and reviewing the last 15 years including 600
      patients who underwent new concepts in primary rhinoplasty out of 1200 patients
      operated during this period, the author analyzes how nasal anatomic layers,
      surgical approaches, and morphological effect of the time interact to modify the
      aesthetic results according to current rhinoplasty concepts. RESULTS: Nasal bony
      cartilaginous vaults biomechanics understanding leads to consider the K-area as a
      flexible joint which can be reshaped without resection of the nasal vaults. The
      role of the subdorsal septum is highlighted as the main anatomic structure which
      can be safely resected in rhinoplasty, and which allows to respect the natural
      anatomy, the nasal valves and the dorsal aesthetic lines. Description of nasal
      compartments divided by the "T" ligament leads to rethink the incisions and
      approaches of the nose: the interseptal-columellar and extended
      infracartilaginous incisions allow to protect nasal ligaments and to perform a
      deep plane undermining. Protection of the anatomic layers allows quick recovery,
      nasal function improvement and long-lasting results. CONCLUSION: The goal to
      reduce the rate of revision rhinoplasty and to improve the natural results can be
      achieved, considering the concept of sequential primary rhinoplasty. Nasal soft
      tissues are protected as far as possible. The current rhinoplasty concepts are
      not antagonist but appear as an intraoperative succession of alternative
      techniques from anatomy and function preservation to reconstruction of the nasal
      framework.

PMID- 29322252
TI  - [Cystic lesions of the jaws].
AB  - Cystic lesions of the jaws comprise a spectrum of inflammatory, developmental and
      neoplastic changes that can clinically appear strikingly similar. Squamous cell
      metaplasia due to superinfection can further blur the histologic hallmarks of the
      individual lesions. In this article an overview of the most important
      differential diagnoses and the novelties of the latest World Health Organisation
      (WHO) classification on head and neck tumours released in early 2017 is provided.
      In contrast to the previous edition, odontogenic cysts have been re-introduced
      and several changes in terminology and taxonomy have been complemented.

PMID- 29322255
TI  - [Electronic vision aids : New options for rehabilitation of the visually
      impaired].
AB  - Due to technical advances, there has been an enormous improvement of electronic
      vision aids in recent years. New developments are especially small portable
      devices which can be easily carried. The majority of electronic vision aids serve
      as a reading aid. Electronic magnifiers are a portable alternative to
      conventional screen readers. In addition, there are mobile reading devices and
      special computer tools. Color recognition devices and barcode scanners are
      helpful in everyday life. Ultrasonic orientation systems enable the recognition
      of obstacles also at head height. Mechanisms incorporated in shoes even comprise
      a navigation system. A brand new development is OrCam (OrCam Technologies Ltd.,
      Israel), a small, inconspicuous camera system which is attached to the
      spectacles. It transmits vision information as a text. Smart phones and tablet
      personal computers have meanwhile been developed to such an extent that they
      replace more expensive special vision aids. Due to the immense technical
      progress, electronic vision aids provide visually impaired people with many
      elegant functions and new possibilities for ophthalmological rehabilitation.
      Besides the technical, mobile and financial aspects, the social acceptance of the
      devices, which should be as unobtrusive as possible, plays an essential role.

PMID- 29322253
TI  - Identification of a mutation in CNNM4 by whole exome sequencing in an Amish
      family and functional link between CNNM4 and IQCB1.
AB  - We investigated an Amish family in which three siblings presented with an early
      onset childhood retinal dystrophy inherited in an autosomal recessive fashion.
      Genome-wide linkage analysis identified significant linkage to marker D2S2216 on
      2q11 with a two-point LOD score of 1.95 and a multi-point LOD score of 3.76.
      Whole exome sequencing was then performed for the three affected individuals and
      identified a homozygous nonsense mutation (c.C1813T, p.R605X) in the cyclin and
      CBS domain divalent metal cation transport mediator 4 (CNNM4) gene located within
      the 2p14-2q14 Jalili syndrome locus. The initial assessment and collection of the
      family were performed before the clinical delineation of Jalili syndrome. Another
      assessment was made after the discovery of the responsible gene and the dental
      abnormalities characteristic of Jalili syndrome were retrospectively identified.
      The p.R605X mutation represents the first probable founder mutation of Jalili
      syndrome identified in the Amish community. The molecular mechanism underlying
      Jalili syndrome is unknown. Here we show that CNNM4 interacts with IQCB1, which
      causes Leber congenital amaurosis (LCA) when mutated. A truncated CNNM4 protein
      starting at R605 significantly increased the rate of apoptosis, and significantly
      increased the interaction between CNNM4 and IQCB1. Mutation p.R605X may cause
      Jalili syndrome by a nonsense-mediated decay mechanism, affecting the function of
      IQCB1 and apoptosis, or both. Our data, for the first time, functionally link
      Jalili syndrome gene CNNM4 to LCA gene IQCB1, providing important insights into
      the molecular pathogenic mechanism of retinal dystrophy in Jalili syndrome.

PMID- 29322254
TI  - The effects of the calcium-magnesium-bicarbonate content in thermal mineral water
      on chronic low back pain: a randomized, controlled follow-up study.
AB  - The aim of this study was to investigate the effects of balneotherapy on chronic
      low back pain. This is a minimized, follow-up study evaluated according to the
      analysis of intention to treat. The subjects included in the study were 105
      patients suffering from chronic low back pain. The control group (n = 53)
      received the traditional musculoskeletal pain killer treatment, while the target
      group (n = 52) attended thermal mineral water treatment for 3 weeks for 15
      occasions on top of the usual musculoskeletal pain killer treatment. The
      following parameters were measured before, right after, and 9 weeks after the 3
      week therapy: the level of low back pain in rest and the level during activity
      are tested using the Visual Analog Scale (VAS); specific questionnaire on the
      back pain (Oswestry); and a questionnaire on quality of life (EuroQual-5D). All
      of the investigated parameters improved significantly (p < 0.001) in the target
      group by the end of the treatment compared to the base period, and this
      improvement was persistent during the follow-up period. There were no significant
      changes in the measured parameters in the control group. Based on our results,
      balneotherapy might have favorable impact on the clinical parameters and quality
      of life of patients suffering from chronic low back pain.

PMID- 29322257
TI  - Repurposing drugs to treat neurological diseases.

PMID- 29322256
TI  - Pilot-scale process development for low-cost production of a thermostable
      biodiesel refining enzyme in Escherichia coli.
AB  - Biodiesels produced from vegetable oils have a major quality problem due to the
      presence of steryl glucosides (SGs), which form precipitates that clog filters
      and cause engine failures. Recently, we described an enzymatic process for
      removing SGs from biodiesel. However, industrial adoption of this technology was
      hindered by the cost of the steryl glucosidase (SGase) enzyme used. Here we
      report the development and validation at the pilot scale of a cost-efficient
      process for manufacturing the SGase. First, we tested various low-cost carbon
      sources for the Escherichia coli producing strain, ultimately developing a fed
      batch fermentation process that utilizes crude glycerol as a feedstock. Next, we
      designed an efficient process for isolating the SGase. That process uses a novel
      thermolysis approach in the presence of a non-ionic detergent, centrifugation to
      separate the solids, and ultrafiltration to concentrate and formulate the final
      product. Our cost analysis indicates that on a large scale, the dose of enzyme
      required to eliminate SGs from each ton of biodiesel will have a manufacturing
      cost below $1. The new process for manufacturing the SGase, which will lead to
      biodiesels of a higher quality, should contribute to facilitate the global
      adoption of this renewable fuel. Our technology could also be used to manufacture
      other thermostable proteins in E. coli.

PMID- 29322258
TI  - Voluntary control of a plegic limb during yawning.

PMID- 29322260
TI  - Minimally invasive opening wedge tibia outpatient osteotomy, using screw-to-plate
      locking technique and a calcium phosphate cement.
AB  - Medial knee osteoarthritis on angular varus deformity of a lower limb is very
      common. Open-wedge high tibial osteotomy is a treatment of choice if cartilage is
      not excessively worn (Allback 1 or 2). The technique based on a plate fixation
      and the bone defect filled with calcium phosphate cement is thoroughly described.
      Data at 1, 3, 6 months and 1 year of a 19 cases continuous and prospective series
      are collected and analysed. Mean age at the time of operation was 55 years. The
      average preoperative varus deformity was 5 degrees  and corrected to an average
      postoperative valgus of 4 degrees  (range 3 degrees -6 degrees ). Each control
      includes the collection of eventual complications, the measurement of health
      status (quality of life and functional scores) and antero-posterior and lateral X
      rays. All osteotomies were considered healed at 6 weeks without any correction
      loss except one, probably result of a technical error. There was no difference in
      clinical and functional results between the group and the literature, but the
      final result occurred earlier in the treatment when the bone defect was filled
      with either calcium phosphate cement. Faster recovery involved no specific
      complication and enabled outpatient treatment in a majority of patients.

PMID- 29322250
TI  - Lactate metabolism: historical context, prior misinterpretations, and current
      understanding.
AB  - Lactate (La-) has long been at the center of controversy in research, clinical,
      and athletic settings. Since its discovery in 1780, La- has often been
      erroneously viewed as simply a hypoxic waste product with multiple deleterious
      effects. Not until the 1980s, with the introduction of the cell-to-cell lactate
      shuttle did a paradigm shift in our understanding of the role of La- in
      metabolism begin. The evidence for La- as a major player in the coordination of
      whole-body metabolism has since grown rapidly. La- is a readily combusted fuel
      that is shuttled throughout the body, and it is a potent signal for angiogenesis
      irrespective of oxygen tension. Despite this, many fundamental discoveries about
      La- are still working their way into mainstream research, clinical care, and
      practice. The purpose of this review is to synthesize current understanding of La
      metabolism via an appraisal of its robust experimental history, particularly in
      exercise physiology. That La- production increases during dysoxia is beyond
      debate, but this condition is the exception rather than the rule. Fluctuations in
      blood [La-] in health and disease are not typically due to low oxygen tension, a
      principle first demonstrated with exercise and now understood to varying degrees
      across disciplines. From its role in coordinating whole-body metabolism as a fuel
      to its role as a signaling molecule in tumors, the study of La- metabolism
      continues to expand and holds potential for multiple clinical applications. This
      review highlights La-'s central role in metabolism and amplifies our
      understanding of past research.

PMID- 29322259
TI  - CSF neurofilament proteins as diagnostic and prognostic biomarkers for
      amyotrophic lateral sclerosis.
AB  - Elevated cerebrospinal fluid (CSF), Neurofilament Light (NF-L) and phosphorylated
      Heavy (pNF-H) chain levels have been found in Amyotrophic Lateral Sclerosis
      (ALS), with studies reporting a correlation of both neurofilaments (NFs) with the
      disease progression. Here, we measured NF-L and pNF-H concentrations in the CSF
      of ALS patients from a single tertiary Center and investigated their relationship
      with disease-related variables. A total of 190 ALS patients (Bulbar, 29.9%;
      Spinal, 70.1%; M/F = 1.53) and 130 controls with mixed neurological diseases were
      recruited. Demographic and clinical variables were recorded, and DeltaFS was used
      to rate the disease progression. Controls were divided into two cohorts: (1)
      patients with non-inflammatory neurological diseases (CTL-1); (2) patients with
      acute/subacute inflammatory diseases and tumors, expected to lead to significant
      axonal and tissue damage (CTL-2). For each patient and control, CSF was taken at
      the time of the diagnostic work-up and stored following the published guidelines.
      CSF NF-L and pNF-H were assayed with commercially available ELISA-based methods.
      Standard curves (from independent ELISA kits) were highly reproducible for both
      NFs, with a coefficient of variation < 20%. We found that CSF NF-L and pNF-H
      levels in ALS were significantly increased when compared to CTL-1 (NF-L: ALS, 4.7
      ng/ml vs CTL-1, 0.61 ng/ml, p < 0.001; pNF-H: ALS, 1.7 ng/ml vs CTL-1, 0.03
      ng/ml, p < 0.0001), but not to CTL-2. Analysis of different clinical and
      prognostic variables disclosed meaningful correlations with both NF-L and pNF-H
      levels. Our results, from a relatively large ALS cohort, confirm that CSF NF-L
      and pNF-H represent valuable diagnostic and prognostic biomarkers in ALS.

PMID- 29322261
TI  - The journey from genetic predisposition to medication overuse headache to its
      acquisition as sequela of chronic migraine.
AB  - Migraine remains one of the biggest clinical case to be solved among the non
      communicable diseases, second to low back pain for disability caused as reported
      by the Global Burden of Disease Study 2016. Despite this, its genetics roots are
      still unknown. Its evolution in chronic forms hits 2-4% of the population and
      causes a form so far defined Medication Overuse Headache (MOH), whose
      pathophysiological basis have not been explained by many dedicated studies. The
      Global Burden of Disease Study 2016 has not recognized MOH as independent entity,
      but as a sequela of Chronic Migraine. This concept, already reported in previous
      studies, has been confirmed by the efficacy of OnabotulinumtoxinA in Chronic
      Migraine independently from the presence of MOH. The consistency of the current
      definitions of both Medication Overuse Headache and Chronic Migraine itself might
      be re-read on the basis of new evidences.

PMID- 29322262
TI  - Partial secretome analysis of Caldariomyces fumago reveals extracellular
      production of the CPO co-substrate H2O2 and provides a coproduction concept for
      CPO and glucose oxidase.
AB  - The culture supernatant of Caldariomyces fumago strains grown in a minimal medium
      with fructose contains mainly the biotechnologically relevant enzyme
      chloroperoxidase (CPO) and only minor amounts of other proteins. Our approach to
      identify the nature of these proteins via peptide mass fingerprinting and
      transcriptome analysis demonstrated the presence of putative glycosyl hydrolase
      and glucose oxidase (GOx) enzymes. These activities had been described earlier as
      parts of the fungus' halogenation machinery, as they provide CPO with the co
      substrate H2O2. The GOx activity was found to have a pH optimum of 5. Compared to
      the wild type values, GOx activity and glucose-driven MCD chlorination activity
      in the culture of a white mutant were found to be strongly increased to values of
      1-2 U mL-1. As most CPO-catalyzed peroxidation reactions also show pH optima at
      around 5, the C. fumago culture supernatant can provide a highly convenient
      CPO/GOx source for many reactions with in situ H2O2 production.

PMID- 29322263
TI  - Comparative transcriptomic analysis of skeletal muscle tissue during prenatal
      stages in Tongcheng and Yorkshire pig using RNA-seq.
AB  - Myogenesis is accompanied by a number of changes in gene expression in mammals,
      and the transcriptional events that underlie these processes have not been yet
      fully elucidated. In this study, RNA-seq was used to comprehensively compare the
      transcription profiles of skeletal muscle between Tongcheng (TC) and Yorkshire
      (YK) pigs at 40, 55, 63, 70, and 90 days of gestation. One thousand three hundred
      seventeen and 691 differentially expressed genes (DEGs) were detected in TC and
      YK, respectively, among which 321 DEGs were shown to be common in TC and YK. STEM
      (Time-series Expression Miner) analysis revealed different gene expression
      profiles between the two breeds. One thousand six hundred seventy-seven genes
      showed significant differential expression between TC and YK at the identical
      stages, while three genes were found to be common in all comparisons. A total of
      3185 new putative transcripts were also predicted. Several gene expression
      profiles were further validated by qRT-PCR. Fifty-five dpc (days post coitum) was
      suggested to be the key stage to contribute developmental differences between TC
      and YK. PTEN, EP300, ENSSSCG00000004979 (Myosin 9A), CDK14, IRS1, PPP1CC, and
      some ribosomal proteins were suggested to be the key candidate genes for
      elucidating the developmental differences between the two breeds. In conclusion,
      we constructed comprehensive high-resolution gene expression maps of these two
      pig breeds, which not only provides an in-depth understanding of the dynamics of
      transcriptional regulation during myogenesis in this study, but also would
      facilitate the elucidation of molecular mechanisms underlying myogenesis in the
      future studies.

PMID- 29322266
TI  - Intraoperative tools for cerebral bypass surgery.

PMID- 29322264
TI  - Cerebral gray matter volume in patients with chronic migraine: correlations with
      clinical features.
AB  - BACKGROUND: To date, few MRI studies have been performed in patients affected by
      chronic migraine (CM), especially in those without medication overuse. Here, we
      performed magnetic resonance imaging (MRI) voxel-based morphometry (VBM) analyses
      to investigate the gray matter (GM) volume of the whole brain in patients
      affected by CM. Our aim was to investigate whether fluctuations in the GM volumes
      were related to the clinical features of CM. METHODS: Twenty untreated patients
      with CM without a past medical history of medication overuse underwent 3-Tesla
      MRI scans and were compared to a group of 20 healthy controls (HCs). We used
      SPM12 and the CAT12 toolbox to process the MRI data and to perform VBM analyses
      of the structural T1-weighted MRI scans. The GM volume of patients was compared
      to that of HCs with various corrected and uncorrected thresholds. To check for
      possible correlations, patients' clinical features and GM maps were regressed.
      RESULTS: Initially, we did not find significant differences in the GM volume
      between patients with CM and HCs (p < 0.05 corrected for multiple comparisons).
      However, using more-liberal uncorrected statistical thresholds, we noted that
      compared to HCs, patients with CM exhibited clusters of regions with lower GM
      volumes including the cerebellum, left middle temporal gyrus, left temporal
      pole/amygdala/hippocampus/pallidum/orbitofrontal cortex, and left occipital areas
      (Brodmann areas 17/18). The GM volume of the cerebellar hemispheres was
      negatively correlated with the disease duration and positively correlated with
      the number of tablets taken per month. CONCLUSION: No gross morphometric changes
      were observed in patients with CM when compared with HCs. However, using more
      liberal uncorrected statistical thresholds, we observed that CM is associated
      with subtle GM volume changes in several brain areas known to be involved in
      nociception/antinociception, multisensory integration, and analgesic dependence.
      We speculate that these slight morphometric impairments could lead, at least in a
      subgroup of patients, to the development and continuation of maladaptive acute
      medication usage.

PMID- 29322267
TI  - Association of decision-making in spinal surgery with specialty and emotional
      involvement-the Indications in Spinal Surgery (INDIANA) survey.
AB  - BACKGROUND: Although recent trials provided level I evidence for the most common
      degenerative lumbar spinal disorders, treatment still varies widely. Thus, the
      Indications in Spinal Surgery (INDIANA) survey explores whether decision-making
      is influenced by specialty or personal emotional involvement of the treating
      specialist. METHOD: Nationwide, neurosurgeons and orthopedic surgeons specialized
      in spine surgery were asked to answer an Internet-based questionnaire with
      typical clinical patient cases of lumbar disc herniation (DH), lumbar spinal
      stenosis (SS), and lumbar degenerative spondylolisthesis (SL). The surgeons were
      assigned to counsel a patient or a close relative, thus creating emotional
      involvement. This was achieved by randomly allocating the surgeons to a patient
      group (PG) and relative group (RG). We then compared neurosurgeons to orthopedic
      surgeons and the PG to the RG regarding treatment decision-making. RESULTS: One
      hundred twenty-two spine surgeons completed the questionnaire (response rate
      78.7%). Regarding DH and SS, more conservative treatment among orthopedic
      surgeons was shown (DH: odds ratio [OR] 4.1, 95% confidence interval [CI] 1.7
      9.7, p = 0.001; SS: OR 3.9, CI 1.8-8.2, p < 0.001). However, emotional
      involvement (PG vs. RG) did not affect these results for any of the three cases
      (DH: p = 0.213; SS: p = 0.097; SL: p = 0.924). CONCLUSIONS: The high response
      rate indicates how important the issues raised by this study actually are for
      dedicated spine surgeons. Moreover, there are considerable variations in decision
      making for the most common degenerative lumbar spinal disorders, although there
      is high-quality data from large multicenter trials available. Emotional
      involvement, though, did not influence treatment recommendations.

PMID- 29322268
TI  - Comment to: Characterization of host response, resorption, and strength
      properties, and performance in the presence of bacteria for fully absorbable
      biomaterials for soft tissue repair. Stoikes NFN, Scott J, Badhwar A, Deeken C,
      Voeller G.

PMID- 29322269
TI  - Prognostic value of simultaneous 18F-FDG PET/MRI using a combination of metabolo
      volumetric parameters and apparent diffusion coefficient in treated head and neck
      cancer.
AB  - BACKGROUND: The aim of this study was to determine the usefulness of combined
      positron emission tomography (PET)/magnetic resonance imaging (MRI) parameters
      provided by simultaneous 18F-fluorodeoxyglucose (FDG) PET/MRI for the prediction
      of treatment failure in surgically resected head and neck cancer. We hypothesized
      that PET parameters corrected by tumor cellularity (combined PET/MRI parameters)
      could predict the prognosis. On regional PET, maximum standardized uptake value
      (SUVmax) was measured as metabolic parameters. In addition, metabolic tumor
      volume (MTV) and total lesion glycolysis (TLG) were checked as metabolo
      volumetric parameters. Mean apparent diffusion coefficient (ADCmean) of tumor was
      evaluated as the MRI parameter on the ADC map. Ratios between metabolic/metabolo
      volumetric parameters and ADC were calculated as combined PET/MRI parameters.
      PET, MRI, and combined PET/MRI parameters were compared with clinicopathologic
      parameters in terms of treatment failure. RESULTS: Seventy-two patients (mean age
      = 55.9 +/- 14.6 year, M: F = 45: 27) who underwent simultaneous 18F-FDG PET/MRI
      before head and neck cancer surgery were retrospectively enrolled. Twenty-two
      patients (30.6%) showed tumor treatment failure after head and neck cancer
      surgery (mean treatment failure = 13.0 +/- 7.0 months). In the univariate
      analysis, MTV (P = 0.044) and ratios between metabolo-volumetric parameters and
      ADC (MTV/ADCmean, P = 0.022; TLG/ADCmean, P = 0.044) demonstrated significance
      among 18F-FDG PET/MRI parameters. Lymphatic invasion (P = 0.044) and perineural
      invasion (P = 0.046) revealed significance among clinicopathologic parameters. In
      the multivariate analysis, MTV (P = 0.026), MTV/ADCmean (P = 0.011), and
      TLG/ADCmean (P = 0.002) with lymphatic invasion (P = 0.026, 0.026, and 0.044,
      respectively) showed significance. CONCLUSIONS: Combined PET/MRI parameters (PET
      metabolo-volumetric parameters corrected by tumor cellularity) could be effective
      predictors of tumor treatment failure after head and neck cancer surgery in
      addition to MTV and clinicopathologic parameter.

PMID- 29322265
TI  - The role of sphingolipids in psychoactive drug use and addiction.
AB  - Psychoactive drug use is a common behavior in many societies worldwide,
      frequently associated with drug instrumentalization. Regular use may develop into
      drug addiction, which is a severe psychiatric disorder with multiple pathological
      effects to virtually all organ systems. Treatment strategies for addiction are
      often insufficient with no broadly working pharmaco-treatment available.
      Recently, lipids, and particularly sphingolipids, have been considered as new
      mediators in the pathogenic pathways and as possible therapeutic targets for the
      treatment of addictive states. In our review, we discuss the contribution of
      sphingolipids in the development of addictive states including alcohol
      consumption, nicotine, amphetamine, morphine, and cocaine dependencies. Recent
      data show that the involvement of various classes of sphingolipids, such as
      sphingomyelins, ceramides, globosides, sulfatides, and cerebrosides, might
      explain the development of some specific features of addictive states, for
      example, apoptotic neurodegeneration induced by psychoactive substances. On the
      other hand, protective effects of sphingolipids are discussed. Sphingolipids
      might be a key mechanism in the development of beneficial effects of moderate
      alcohol consumption. Therefore, sphingolipid systems emerge as possible new
      pathways involved in the development of addiction and its pathophysiological
      consequences. However, further analysis is still needed to investigate the exact
      mechanisms of sphingolipid contribution and possibility of using of sphingolipids
      as new therapeutic targets.

PMID- 29322271
TI  - Responses of macroinvertebrate communities to pesticide application in irrigated
      rice fields.
AB  - The ability to recover to original states after disturbances makes
      macroinvertebrates useful tools for assessing the impacts of pesticides. Many
      studies showed that direct exposure to pesticides decreases macroinvertebrate
      richness and alters their composition. The main objective of this study was to
      assess recovery patterns in macroinvertebrate communities after pesticide
      application in irrigated rice fields. We analyzed short-term temporal dynamics of
      macroinvertebrate communities after application of the herbicides bispyribac
      sodium and clomazone and the insecticide chlorantraniliprole, over the rice
      growing season in southern Brazil. We selected three conventional rice fields and
      the recovery of macroinvertebrate communities was also compared with three
      adjacent natural ponds. The study was developed from November 2011 to February
      2012 (rice-growing season). Five macroinvertebrate collections were carried out
      3, 7, 14, 38, and 60 days after pesticide application (November 25). Rice fields
      showed lower richness and abundance than ponds in the period immediately after
      pesticide application, and recovery rates in the richness of macroinvertebrate
      communities were more conspicuous as pesticide residuals dissipated from the
      fields. Macroinvertebrate community structure in rice fields also became more
      similar to natural ponds as pesticide traces were scarcer. However,
      macroinvertebrate abundance patterns were not related to pesticide concentrations
      in the fields. Our results supported the general hypothesis on the negative
      effects of pesticide application on macroinvertebrate community in irrigated rice
      fields, although other environmental features (e.g., length of the flooded
      period) also contributed to explain temporal dynamics in the macroinvertebrate
      communities from irrigated rice fields.

PMID- 29322272
TI  - A novel passerivirus (family Picornaviridae) in an outbreak of enteritis with
      high mortality in estrildid finches (Uraeginthus sp.).
AB  - An enteric outbreak with high mortality (34/52, 65.4%) was recorded in 2014 in
      home-reared estrildid finches (Estrildidae) in Hungary. A novel passerivirus was
      identified in a diseased violet-eared waxbill using viral metagenomics and
      confirmed by RT-(q)PCR. The complete genome of finch picornavirus strain
      waxbill/DB01/HUN/2014 (MF977321) showed the highest amino acid sequence identity
      of 38.9%, 61.6%, 69.6% in P1cap, 2Chel and 3CproDpol, respectively, to
      passerivirus A1 (GU182406). A high viral load (6.58 * 1010 genomic copies/ml) was
      measured in a cloacal specimen and in the tissues (spinal cord, lung, and the
      intestines) of two additional affected finches. In addition to intestinal
      symptoms (diarrhoea), the presence of extra-intestinal virus suggests a
      generalized infection in this fatal disease, for which the passerivirus might be
      a causative agent.

PMID- 29322270
TI  - Recent developments in evaluation and treatment of lateral patellar instability.
AB  - Recent years have been characterized by an ongoing increase in knowledge about
      the different conditions associated with lateral patellar instability. This
      increase in knowledge provides differentiated approaches to the various
      pathologies of the patellofemoral joint. Though current guidelines consider
      medial patellofemoral ligament (MPFL) reconstruction the basic treatment for the
      unstable patella, medial soft tissue-stabilizing procedures should not be
      interpreted as stand-alone procedures in every case. The influence of different
      anatomical factors leading to patellar instability, as well as their impact on
      clinical outcome measures, is becoming increasingly apparent and deserves further
      attention. Therefore, the purpose of this review was to summarize recent
      developments in lateral patellar instability beyond MPFL reconstruction
      techniques. For this goal, the literature published within the last 3 years
      considering all aspects of lateral patellar instability was analysed. Six main
      topics evolved according to the number of publications and in terms of novel
      aspects and recent developments in the evaluation and treatment of lateral
      patellar instability. Those topics formed the basis of this article: (1)
      treatment of first-time patellar dislocation, (2) the impact of trochlear
      dysplasia and trochleoplasty procedures, (3) the relevance of torsional
      deformities, (4) patellar instability in open physis, (5) the implementation of
      new outcome measures, and (6) rehabilitation after patellar stabilizing
      procedures.

PMID- 29322273
TI  - The emerging influenza virus threat: status and new prospects for its therapy and
      control.
AB  - Influenza A viruses (IAVs) are zoonotic pathogens that cause yearly outbreaks
      with high rates of morbidity and fatality. The virus continuously acquires point
      mutations while circulating in several hosts, ranging from aquatic birds to
      mammals, including humans. The wide range of hosts provides influenza A viruses
      greater chances of genetic re-assortment, leading to the emergence of zoonotic
      strains and occasional pandemics that have a severe impact on human life. Four
      major influenza pandemics have been reported to date, and health authorities
      worldwide have shown tremendous progress in efforts to control epidemics and
      pandemics. Here, we primarily discuss the pathogenesis of influenza virus type A,
      its epidemiology, pandemic potential, current status of antiviral drugs and
      vaccines, and ways to effectively manage the disease during a crisis.

PMID- 29322274
TI  - Evidence of clinical and economic impact of pharmacist interventions related to
      antimicrobials in the hospital setting.
AB  - The purpose of this paper was to review the literature regarding the clinical and
      economic impact of pharmacist interventions (PIs) related to antimicrobials in
      the hospital setting. A PubMed literature search from January 2003 to March 2016
      was conducted using the terms pharmacist* or clinical pharmacist* combined with
      antimicrobial* or antibiotic* or anti-infective*. Comparative studies that
      assessed the clinical and/or economic impact of PIs on antimicrobials in the
      hospital setting were reviewed. Outcomes were classified as: treatment-related
      outcomes (TROs), clinical outcomes (COs), cost and microbiological outcomes
      (MOs). Acceptance of pharmacist recommendations by physicians was collected. PIs
      were grouped into patient-specific recommendations (PSRs), policy, and education.
      Studies' risk of bias was analyzed using Cochrane's tool. Twenty-three studies
      were evaluated. All of them had high risk of bias. The design in most cases was
      uncontrolled before and after. PSRs were included in every study; five also
      included policy and four education. Significant impact of PI was found in 14 of
      the 18 studies (77.8%) that evaluated costs, 15 of the 20 studies (75.0%) that
      assessed TROs, 12 of the 22 studies (54.5%) that analyzed COs, and one of the two
      studies (50.0%) that evaluated MOs. None of the studies found significant
      negative impact of PIs. It could not be concluded that adding other strategies to
      PSRs would improve results. Acceptance of recommendations varied from 70 to
      97.5%. Pharmacists improve TROs and COs, and decrease costs. Additional research
      with a lower risk of bias is unlikely to change this conclusion. Future research
      should focus on identifying the most efficient interventions.

PMID- 29322275
TI  - Outcome of polymerase chain reaction (PCR) analysis in 100 suspected cases of
      infectious uveitis.
AB  - BACKGROUND: Polymerase chain reaction (PCR) analysis is an important tool in the
      diagnosis of infectious uveitis. A retrospective, interventional study of PCR
      analysis of ocular fluid in suspected infectious uveitis cases between January
      2014 to July 2016 was done. Nested, real-time and broad range PCR was performed
      for detection of the genome of Mycobacterium tuberculosis, herpes virus family,
      Chikungunya virus, Toxoplasma gondii, fungus, eubacterium and propionibacterium
      acne. RESULTS: Total of 100 cases included, mean age was 39.2 +/- 15.4 years.
      Uveitis was unilateral in 82% and granulomatous in 40%. Mean visual acuity at the
      initial visit and final visit was 0.73 logMar and 0.63 logMar respectively. PCR
      analysis confirmed the clinical diagnosis in 70.1% patients. The sensitivity,
      specificity, positive predictive value and negative predictive value of PCR
      analysis was 90.2%, 93.9%, 93.9% and 90.2% respectively. The quantitative value
      of real-time M. tb. Positive PCR ranged from 32c/ml to 2722 c/ml. CONCLUSIONS:
      PCR assay is an accurate technique with high sensitivity and specificity to
      diagnose the DNA genome in infectious uveitis.

PMID- 29322276
TI  - Integrating direct observation and GPS tracking to monitor animal behavior for
      resource management.
AB  - Monitoring the behavior of pack animals in protected areas informs management
      about use patterns and the potential associated negative impacts. However,
      systematic assessments of behavior are uncommon due to methodological and
      logistical constraints. This study integrated behavior mapping with GPS tracking,
      and applied behavior change point analysis, as an approach to monitor the
      behaviors of pack animals during overnight periods. The integrated approach
      identified multiple grazing patterns (i.e., locally intense grazing, ambulatory
      grazing) not feasible through a single methodology alone. Monitoring behavior and
      corresponding environmental conditions aid managers in implementing strategies
      designed to mitigate impacts associated with pack animals in natural areas.
      Results also contrast the influence of temporal scale on behavior segmentation to
      inform decisions for further monitoring and management of domestic animal use and
      impacts in natural areas. This integrated approach reduced time and logistical
      constraints of each method individually to promote ongoing monitoring and
      highlight how multiple management tactics could reduce impacts to sensitive
      habitats.

PMID- 29322277
TI  - Language Delay and Externalizing Problems in Preschool Age: A Prospective Cohort
      Study.
AB  - This study sought to examine the direction of causation between language delay
      and two externalizing problems; inattention and aggression. Autoregressive fixed
      effects models were fitted to data from 25,474 children (age 1.5 to 5 years;
      50.8% boys) in the population-based longitudinal Norwegian Mother and Child
      Cohort Study (MoBa), to model the direction of causality for language delay and
      inattention and aggression, respectively. The most parsimonious model for the
      relationship between language delay and inattention was one where both common
      factors and reciprocal causation were estimated. Adjusted for common factors,
      language delay was estimated to have a non-significant effect on inattention by b
      = 0.12 (p = 0.06), and inattention to have a significant effect on language delay
      by b = 0.19 (p = 0.03). The most parsimonious model for the direction of
      causality for language delay and aggression was one where the entire association
      could be explained by language delay having effect on aggression b = 0.12 (p <
      0.02). It appears that while language delay can best be conceptualized as an
      epiphenomenon of inattention partly related to both common factors and causal
      processes, aggression can best be conceptualized as caused by language delay.
      This illumination of the hypothetical causal links between two common problem
      domains in preschool-aged children has clear implications on where to implement
      interventions to prevent co-occurrence of language delay and externalizing
      problems.

PMID- 29322278
TI  - Impacts of chronic non-communicable diseases on households' out-of-pocket
      healthcare expenditures in Sri Lanka.
AB  - This article examines the effects of chronic non-communicable diseases (NCDs) on
      households' out-of-pocket health expenditures in Sri Lanka. We explore the
      disease specific impacts on out-of-pocket health care expenses from chronic NCDs
      such as heart diseases, hypertension, cancer, diabetics and asthma. We use
      nationwide cross-sectional household income and expenditure survey 2012/2013 data
      compiled by the department of census and statistics of Sri Lanka. Employing
      propensity score matching method to account for selectivity bias, we find that
      chronic NCD affected households appear to spend significantly higher out-of
      pocket health care expenditures and encounter grater economic burden than matched
      control group despite having universal public health care policy in Sri Lanka.
      The results also suggest that out-of-pocket expenses on medicines and other
      pharmaceutical products as well as expenses on medical laboratory tests and other
      ancillary services are particularly higher for households with chronic NCD
      patients. The findings underline the importance of protecting households against
      the financial burden due to NCDs.

PMID- 29322279
TI  - Do the more educated utilize more health care services? Evidence from Vietnam
      using a regression discontinuity design.
AB  - In 1991, Vietnam implemented a compulsory primary schooling reform that provides
      this study a natural experiment to estimate the causal effect of education on
      health care utilization with a regression discontinuity design. This paper finds
      that education causes statistically significant impacts on health care
      utilization, although the signs of the impacts change with specific types of
      health care services examined. In particular, education increases the inpatient
      utilization of the public health sector, but it reduces the outpatient
      utilization of both the public and private health sectors. The estimates are
      strongly robust to various windows of the sample choice. The paper also discovers
      that the links between education and the probability of health insurance and
      income play essential roles as potential mechanisms to explain the causal impact
      of education on health care utilization in Vietnam.

PMID- 29322281
TI  - Carbon dioxide absorbents: does it matter which one you use?

PMID- 29322282
TI  - 1st UK Interdisciplinary Breast Cancer Symposium-15th-16th January 2018.

PMID- 29322283
TI  - Rational design of engineered microbial cell surface multi-enzyme co-display
      system for sustainable NADH regeneration from low-cost biomass.
AB  - As an important cofactor, NADH is essential for most redox reactions and biofuel
      cells. However, supply of exogenous NADH is challenged, due to the low production
      efficiency and high cost of NADH regeneration system, as well as low stability of
      NADH. Here, we constructed a novel cell surface multi-enzyme co-display system
      with ratio- and space-controllable manner as exogenous NADH regeneration system
      for the sustainable NADH production from low-cost biomass. Dockerin-fused
      glucoamylase (GA) and glucose dehydrogenase (GDH) were expressed and assembled on
      the engineered bacterial surfaces, which displayed protein scaffolds with various
      combinations of different cohesins. When the ratio of GA and GDH was 3:1, the
      NADH production rate of the whole-cell biocatalyst reached the highest level
      using starch as substrate, which was three times higher than that of mixture of
      free enzymes, indicating that the highly ordered spatial organization of enzymes
      would promote reactions, due to the ratio of enzymes and proximity effect. To
      confirm performance of the established NADH regeneration system, the highly
      efficient synthesis of L-lactic acid (L-LA) was conducted by the system and the
      yield of L-LA (16 g/L) was twice higher than that of the mixture of free enzymes.
      The multi-enzyme co-display system showed good stability in the cyclic
      utilization. In conclusion, the novel sustainable NADH system would provide a
      cost-effective strategy to regenerate cofactor from low-cost biomass.

PMID- 29322284
TI  - Identification of Concepts of Spiritual Care in Iranian Peoples with Multiple
      Sclerosis: A Qualitative Study.
AB  - Living with multiple sclerosis (MS) often needs attention combined with receiving
      the holistic care. Attention to spiritual care dimension is one of the most
      important aspects of care for these patients. This study aims at exploring and
      explaining dimensions of spiritual care for MS patients in care system of Iran.
      This study is conducted to explore the concept of spiritual care in care system
      of Iran during 2015-2016. Purposive sampling is done on 25 participants through
      unstructured interviews and observation of obtained data through conventional
      content analysis approach. Four themes of participants' experiences in spiritual
      care include restoration of identity essence and nature; disease as a factor for
      nearness to God; giving meaning to life; and disease as a facilitator for self
      purification. Clear understanding of spiritual care dimensions and promoting
      knowledge in MS nurses as the caregivers play important roles in achieving the
      goals of health among patients in different cultures and religions. Given the
      results of this study, the themes such as the restoration of identity essence and
      nature, the disease as a factor for nearness to God, giving meaning to life and
      the disease as a facilitator for self-purification play important roles in
      explaining the concept of spiritual care in patients with MS. Therefore, the MS
      nurses and other health professionals need to effectively and successfully
      integrate the concept of spiritual care with their professional performance by
      deep understanding of this concept and try to provide holistic care to respond to
      MS patients' intertwined needs.

PMID- 29322280
TI  - Direct cardiovascular impact of SGLT2 inhibitors: mechanisms and effects.
AB  - Diabetes is a global epidemic and a leading cause of death with more than 422
      million patients worldwide out of whom around 392 million alone suffer from type
      2 diabetes (T2D). Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are novel
      and effective drugs in managing glycemia of T2D patients. These inhibitors gained
      recent clinical and basic research attention due to their clinically observed
      cardiovascular protective effects. Although interest in the study of various SGLT
      isoforms and the effect of their inhibition on cardiovascular function extends
      over the past 20 years, an explanation of the effects observed clinically based
      on available experimental data is not forthcoming. The remarkable reduction in
      cardiovascular (CV) mortality (38%), major CV events (14%), hospitalization for
      heart failure (35%), and death from any cause (32%) observed over a period of 2.6
      years in patients with T2D and high CV risk in the EMPA-REG OUTCOME trial
      involving the SGLT2 inhibitor empagliflozin (Empa) have raised the possibility
      that potential novel, more specific mechanisms of SGLT2 inhibition synergize with
      the known modest systemic improvements, such as glycemic, body weight, diuresis,
      and blood pressure control. Multiple studies investigated the direct impact of
      SGLT2i on the cardiovascular system with limited findings and the
      pathophysiological role of SGLTs in the heart. The direct impact of SGLT2i on
      cardiac homeostasis remains controversial, especially that SGLT1 isoform is the
      only form expressed in the capillaries and myocardium of human and rodent hearts.
      The direct impact of SGLT2i on the cardiovascular system along with potential
      lines of future research is summarized in this review.

PMID- 29322285
TI  - A Longitudinal Study of Religiosity, Spiritual Health Locus of Control, and
      Health Behaviors in a National Sample of African Americans.
AB  - The present longitudinal study examined religious beliefs and behaviors,
      spiritual health locus of control (SHLOC), and selected health-related behaviors
      and outcomes in a national sample of 766 African American adults. Participants
      were interviewed by telephone three times over a 5-year period. Results indicated
      that stronger religious beliefs and religious behaviors were associated with
      greater changes in active SHLOC. There was some evidence of direct effects of
      religious beliefs and behaviors on changes in health behaviors. Religious
      behaviors were related to greater passive SHLOC over time across some health
      outcomes. Passive SHLOC was associated with some less desirable health outcomes
      over time.

PMID- 29322287
TI  - Metaplastic Breast Cancer: Practice Patterns, Outcomes, and the Role of
      Radiotherapy.
AB  - PURPOSE: Metaplastic breast cancer (MBC) is a rare, aggressive form of breast
      cancer with limited data to guide management. This study of a large, contemporary
      US database described national practice patterns and addressed the impact of
      radiotherapy (RT) on survival. METHODS: The National Cancer Data Base was queried
      (2004-2013) for women with non-metastatic MBC. Multivariable logistic regression
      ascertained factors associated with RT administration. Kaplan-Meier analysis
      evaluated overall survival (OS) between patients treated with either lumpectomy
      or mastectomy with or without RT, while substratifying patients into pT1-2N0 and
      pT3-4/N+ subcohorts. Cox proportional hazards modeling determined variables
      associated with OS. RESULTS: Of 5211 total patients, 447 (9%) had lumpectomy
      alone, 1831 (35%) had post-lumpectomy RT, 2020 (39%) had mastectomy alone, and
      913 (18%) had post-mastectomy RT (PMRT). Most patients underwent chemotherapy
      (79%), and mastectomy was the most common surgical approach (56%). RT delivery
      was impacted by many factors, including higher nodal disease (p < 0.001), but not
      T classification or estrogen receptor status (p > 0.05 for both). Post-lumpectomy
      RT was associated with higher OS in both the pT1-2N0 and pT3-4/N+ subsets (p <
      0.001 for both), while PMRT was associated with OS benefits in pT3-4/N+ cases (p
      < 0.001), but not in pT1-2N0 cases (p = 0.259). CONCLUSIONS: In the largest study
      to date evaluating MBC, practice patterns of surgery, systemic therapy, and RT
      are described. The addition of RT in the post-lumpectomy setting was associated
      with higher OS, in addition to pT3-4/N+ in the post-mastectomy setting. Although
      not implying causation, further work is required to corroborate the conclusions
      herein.

PMID- 29322288
TI  - An Exploration of How Simulated Gambling Games May Promote Gambling with Money.
AB  - Portable media devices, such as smartphones, have allowed gambling related
      content to infiltrate into a new market of potential consumers. Simulated
      gambling products are now readily available through multiple online platforms,
      and are becoming a popular form of entertainment for many young media users.
      Despite widespread use of these products, very little is known about how
      continued exposure to and involvement with simulated gambling may impact on real
      money gambling attitudes and behaviours, particularly for young consumers. This
      paper reviews the literature exploring simulated gambling products and how
      consumption may promote monetary gambling, as well as fostering pro-gambling
      attitudes among youth and adolescents. Findings suggest that youth are highly
      exposed to simulated gambling games, and those who engage with these products are
      also more likely to be prone to monetary gambling and gambling problems. Virtual
      currency, in-game events and gambling themed content are also likely to promote
      biases about gambling or desensitise consumers to monetary losses. Simulated
      gambling products may therefore pose a risk to consumers, and particularly young
      consumers, rather than serve as a benign substitute for monetary gambling. To
      date, research has largely focused on correlational relationships between
      simulated and monetary gambling using cross-sectional methodologies. Future
      research should focus on determining the causal pathway between simulated
      gambling involvement and monetary gambling in order to identify and manage any
      risk associated simulated gambling participation.

PMID- 29322289
TI  - The Interaction Between Asthma and Anxiety: An Interpretative Phenomenological
      Analysis of Young People's Experiences.
AB  - Asthma and anxiety are highly co-morbid, and their interaction leads to
      exacerbations for both conditions. This study explored the interplay between
      these two conditions from the perspective of children and adolescents. The
      objective was to identify potential mechanisms of interaction between asthma and
      anxiety, and to derive improvements for prevention and treatment. Eleven semi
      structured interviews of young people (aged 11-15), who met criteria for both
      asthma and anxiety, were analysed using interpretative phenomenological analysis.
      Well-established qualitative research recommendations were followed to promote
      credibility and rigour in the findings. Eight themes emerged that were organised
      in three domains: (i) asthma affecting anxiety by inhibiting coping activities or
      developmental tasks and by triggering unhelpful thinking and behaviour; (ii)
      anxiety affecting asthma by impairing self-care and triggering hyperventilation;
      (iii) interactions between asthma and anxiety, including self-perpetuating
      feedback cycles and symptom confusion. The proposed mechanisms could help tailor
      cognitive-behavioural interventions to reduce anxiety and asthma complications.

PMID- 29322286
TI  - Hyperglycemia and aberrant O-GlcNAcylation: contributions to tumor progression.
AB  - A number of cancer types have shown an increased prevalence and a higher
      mortality rate in patients with hyperglycemic associated pathologies. Although
      the correlation between diabetes and cancer incidence has been increasingly
      reported, the underlying molecular mechanisms beyond this association are not yet
      fully understood. Recent studies have suggested that high glucose levels support
      tumor progression through multiple mechanisms that are hallmarks of cancer,
      including cell proliferation, resistance to apoptosis, increased cell migration
      and invasiveness, epigenetic regulation (hyperglycemic memory), resistance to
      chemotherapy and altered metabolism. Most of the above occur because
      hyperglycemia through hexosamine biosynthetic pathway leads to aberrant O
      GlcNAcylation of many intracellular proteins that are involved in those
      mechanisms. Deregulated O-GlcNAcylation is emerging as a general feature of
      cancer. Despite strong evidence suggesting that aberrant O-GlcNAcylation is or
      may be involved in the acquisition of all cancer hallmarks, it remains out of the
      list of the next generation of emerging hallmarks. Here, we discuss some of the
      current understanding on how hyperglycemia affects cancer cell biology and how
      aberrant O-GlcNAcylation stands in this context.

PMID- 29322290
TI  - Psychologists and Pediatricians in the Primary Care Sandbox: Communication is Key
      to Cooperative Play.
AB  - Recent literature, public policy, and funding opportunities call attention to the
      need for better increased integration of health and mental health care services
      in primary care settings so as to best meet the needs of children and families.
      There are many benefits to such integration, but pediatric primary care providers
      (PCPs) face multiple barriers to identifying and managing patients with mental
      health difficulties. One way to address this problem is through the integration
      of psychologists into primary care settings who can collaborate with PCPs to
      provide integrated behavioral health care to youth and families. However, there
      are challenges to collaboration, which include differences in training,
      professional cultures, and expectations held by professionals from various
      disciplines. Effective communication is a key component in supporting
      interprofessional collaboration between primary care providers and psychologists
      working in primary care settings. This paper reviews aspects of pediatric
      medicine culture, critical components of communication, and strategies to improve
      communication. Three case examples are presented in which some of these
      challenges have been successfully addressed. Implications and future directions
      are discussed.

PMID- 29322291
TI  - Personality Pathology in Primary Care: Ongoing Needs for Detection and
      Intervention.
AB  - Recent studies demonstrate that personality disorders are prevalent within
      outpatient psychiatry clinics, though they also are quite common in primary care
      settings. Studies across multiple health care settings demonstrate that those
      with a known PD have higher incidences of health problems, higher utilization of
      the health care system, and have a life expectancy 17.7 years less than that of
      the population in general. Despite these data, little attention has been directed
      toward detecting, managing, and treating patients with personality pathology in
      primary care settings. Consequently, it is argued that more attention be devoted
      to detecting PDs in this population, training physicians and primary care
      professionals in the rapid screening of personality pathology, the management of
      patients with personality pathology, and utilizing behavioral health specialists
      and reliable referral sources to address these problems as part of their overall
      health care management. Suggestions for how to implement these ideas are offered.

PMID- 29322293
TI  - Correction to: CALB-Catalyzed Two-Step Alcoholytic Desymmetrization of 3
      Methylglutaric Diazolides in MTBE.
AB  - The original version of this article unfortunately contained a mistake in Eq. 3.

PMID- 29322292
TI  - Bilateral symmetrical comparison of the proximal femur using 3D-CT models.
AB  - PURPOSE: Superimposed three-dimensional (3D)-models obtained from CT-images have
      been used to evaluate displacement of femoral neck fractures, but this method
      assumes symmetrical anatomy of normal femurs. The present study aimed to compare
      the spatial orientation of the left and right proximal femur, thus establishing
      if 3D models can be used as a reference standard for the evaluation of fracture
      displacement. METHODS: We generated 3D-CT-models of 20 patients with no skeletal
      pathology of the proximal femurs. Three observers independently determined the
      positions of the fovea and the femoral head, and a vector intersecting the centre
      points of the fovea and the femoral head defined the rotation. Differences in
      positions and rotations were determined by superimposing the 3D-CT-models of both
      femurs. RESULTS: The mean distance (95% CI) between positions of the left and
      right fovea was 3.1 mm (2.7-3.4) and between the left and right femoral head 2.8
      mm (2.6-3.0). The minimal detectable change was 2.8 for the fovea and 2.3 for the
      femoral head, and the repeatability coefficients between 2.1-2.7 and 1.0-2.9,
      respectively. Mean difference in rotation of the femoral head was 6 degrees  (5.3
      6.6) with a minimal detectable change of 8.8 and repeatability coefficients
      ranging from 5.8 to 10.0. CONCLUSIONS: Distances between the left and right
      femoral heads were larger than what could be explained by measurement error
      alone, suggesting that there may be minor side-to-side differences. However,
      these differences are small, and 3D-CT-models can be used as a reference standard
      to evaluate displacement of femoral neck fractures.

PMID- 29322295
TI  - Correction to: Epidemiology of chronic hepatitis B virus in Ireland using
      routinely collected surveillance and administrative data, 2004-2014.
AB  - The original version contained a mistake. The published version of this article
      incorrectly lists Lelia Thornton as Thornton Thornton. The correct author name is
      presented above.

PMID- 29322294
TI  - Ticagrelor inhibits platelet-tumor cell interactions and metastasis in human and
      murine breast cancer.
AB  - Activated platelets promote the proliferation and metastatic potential of cancer
      cells. Platelet activation is largely mediated through ADP engagement of
      purinergic P2Y12 receptors on platelets. We examined the potential of the
      reversible P2Y12 inhibitor ticagrelor, an agent used clinically to prevent
      cardiovascular and cerebrovascular events, to reduce tumor growth and metastasis.
      In vitro, MCF-7, MDA-MB-468, and MDA-MB-231 human mammary carcinoma cells
      exhibited decreased interaction with platelets treated with ticagrelor compared
      to untreated platelets. Prevention of tumor cell-platelet interactions through
      pretreatment of platelets with ticagrelor did not improve natural killer cell
      mediated tumor cell killing of K562 myelogenous leukemia target cells.
      Additionally, ticagrelor had no effect on proliferation of 4T1 mouse mammary
      carcinoma cells co-cultured with platelets, or on primary 4T1 tumor growth. In an
      orthotopic 4T1 breast cancer model, ticagrelor (10 mg/kg), but not clopidogrel
      (10 mg/kg) or saline, resulted in reduced metastasis and improved survival.
      Ticagrelor treatment was associated with a marked reduction in tumor cell
      platelet aggregates in the lungs at 10, 30 and 60 min post-intravenous
      inoculation. These findings suggest a role for P2Y12-mediated platelet activation
      in promoting metastasis, and provide support for the use of ticagrelor in the
      prevention of breast cancer spread.

PMID- 29322296
TI  - Catheter-directed, ultrasound-facilitated fibrinolysis in obese patients with
      massive and submassive pulmonary embolism.
AB  - Obesity is a well-established risk factor for pulmonary embolism (PE). However,
      treatment of PE in obese patients is challenging because of limited outcomes
      data, especially with advanced therapies such as catheter-based fibrinolysis. We
      assessed the efficacy and safety of ultrasound-facilitated, catheter-directed
      fibrinolysis in obese patients with submassive and massive PE enrolled in the
      SEATTLE II Trial. Eligible patients had a right ventricular-to-left ventricular
      (RV/LV) diameter ratio >= 0.9 on chest computed tomography (CT). The primary
      efficacy outcome was the change in chest CT-measured RV/LV diameter ratio at 48 h
      after procedure initiation. The primary safety outcome was GUSTO major bleeding
      within 72 h. One-hundred and four patients were obese, as defined by a BMI >= 30
      kg/m2, and 44 were non-obese. Mean RV/LV ratio was greater in obese patients at
      baseline compared with non-obese patients (1.60 vs. 1.43, p = 0.02). Reduction in
      RV/LV diameter ratio at 48 h was greater in obese patients compared with non
      obese patients (absolute reduction: - 0.47 vs. - 0.30, p = 0.01; relative
      reduction: - 26 vs. - 18%, p = 0.03). Major bleeding occurred in 12 (12%) of
      obese patients and in 3 (7%) in non-obese patients (p = 0.55). In conclusion,
      ultrasound-facilitated, catheter-directed fibrinolysis shows promise in obese
      patients for whom advanced therapy for acute PE is warranted.

PMID- 29322297
TI  - Nuclear distribution of the Trypanosoma cruzi RNA Pol I subunit RPA31 during
      growth and metacyclogenesis, and characterization of its nuclear localization
      signal.
AB  - Trypanosoma cruzi is the aetiologic agent of Chagas disease. Our research group
      studies ribosomal RNA (rRNA) gene transcription and nucleolus dynamics in this
      species of trypanosomes. RPA31 is an essential subunit of RNA polymerase I (Pol
      I) whose presence is apparently restricted to trypanosomes. Using fluorescent
      tagged versions of this protein (TcRPA31-EGFP), we describe its nuclear
      distribution during growth and metacyclogenesis. Our findings indicate that
      TcRPA31-EGFP alters its nuclear presence from concentrated nucleolar localization
      in exponentially growing epimastigotes to a dispersed granular distribution in
      the nucleoplasm of stationary epimastigotes and metacyclic trypomastigotes. These
      changes likely reflect a structural redistribution of the Pol I transcription
      machinery in quiescent cellular stages where downregulation of rRNA synthesis is
      known to occur. In addition, and related to the nuclear internalization of this
      protein, the presence of a classical bipartite-type nuclear localization signal
      was identified towards its C-terminal end. The functionality of this motif was
      demonstrated by its partial or total deletion in recombinant versions of the
      tagged fluorescent protein. Moreover, ivermectin inhibited the nuclear
      localization of the labelled chimaera, suggesting the involvement of the importin
      alpha/beta transport system.

PMID- 29322298
TI  - A new microsporidium Fibrillaspora daphniae g. n. sp. n. infecting Daphnia magna
      (Crustacea: Cladocera) in Siberia and its taxonomic placing within a new family
      Fibrillasporidae and new superfamily Tubulinosematoidea (Opisthosporidia:
      Microsporidia).
AB  - Infection with a new microsporidium, Fibrillaspora daphniae g. n. sp. n., was
      found in a local Daphnia magna population in Tomsk region (Western Siberia,
      Russia) at the prevalence rate of 52%. Histological sections showed parasite
      cells entirely encompassing the host haemocoel. Methanol-fixed spores were
      elongate, oval, 4.8 +/- 0.3 MUm * 2.3 +/- 0.2 MUm in size. All developmental
      stages were in direct contact with the host cell cytoplasm, with single nuclei,
      and division by binary fission. The sporont surface was covered with an
      additional outer layer composed of fine tubules. The spores possessed a thick
      endospore, large posterior vacuole filled with electron-dense granules, and a
      bipartite polaroplast composed of anterior lamellar and posterior globular
      elements. The polar tube was slightly anisofilar, with 13-19 coils arranged in
      one row; the two posterior coils were of lesser diameter. The small subunit
      ribosomal RNA gene sequence was deposited in Genbank under accession # MF278272.
      Considering the sister relationship between Fibrillanosema crangonycis and our
      new isolate described here as Fibrillaspora daphniae, we propose a new family
      Fibrillasporidae fam. n. to contain these two genera and the descendants of their
      common ancestor. A new superfamily Tubulinosematoidea superfam. n. is proposed as
      a monophyletic assemblage of Fibrillasporidae fam. n. and Tubulinosematidae.

PMID- 29322299
TI  - Serum Parathyroid Hormone and 25-Hydroxyvitamin D Concentrations Before and After
      Biliopancreatic Diversion.
AB  - BACKGROUND: Biliopancreatic diversion with duodenal switch (BPD-DS) decreases
      vitamin D and calcium absorption, which may result in secondary
      hyperparathyroidism. This study aimed at evaluating the prevalence of vitamin D
      deficiency and secondary hyperparathyroidism before and after BPD-DS. METHODS: A
      retrospective analysis of patients who had undergone BPD-DS at a tertiary
      bariatric center between 2003 and 2010 and for whom simultaneous measurements of
      serum 25-hydroxyvitamin D and parathyroid hormone were available within 5 years
      post-op was performed. The prevalence of vitamin D deficiency (< 20 ng/ml) and
      secondary hyperparathyroidism (> 65 pg/mL) at different time points was
      calculated. RESULTS: Included were 1436 patients (mean +/- SD, age 42.7 +/- 10.4
      years; BMI 51.5 +/- 8.6 kg/m2; 69.8% women). Prevalence of vitamin D deficiency
      decreased up to 6-12 months after surgery (from 35.8% at baseline down to 6-9%)
      then rose progressively, plateauing at 15.5% after 36 months. Prevalence of
      hyperparathyroidism was 28.5% before surgery and rose progressively after
      surgery, reaching 68.6% at 5 years. Mean serum corrected calcium increased from 0
      to 6 months then decreased up to 36 months. Preoperatively, the prevalence of
      hypocalcemia was 7.3%. It increased after 12 months, attaining 26.9% at 48
      months. CONCLUSIONS: Prevalence of vitamin D deficiency and secondary
      hyperparathyroidism is high before BPD-DS. Despite a low prevalence of vitamin D
      deficiency after surgery, prevalence of hyperparathyroidism increased steadily 1
      year after surgery, preceded by a decrease in serum calcium. Factors explaining
      the high prevalence of secondary hyperparathyroidism after BPD-DS and its long
      term impact on bone health should be addressed.

PMID- 29322300
TI  - Glycemic control in type 2 diabetes: from medication nonadherence to residual
      vascular risk.
AB  - Despite the availability of many new treatment options for type 2 diabetes, the
      proportion of patients achieving the HbA1c target < 7.0% remains around 50%. We
      put forward the hypothesis that the unchanged HbA1c results, observed in the last
      decade in type 2 diabetes patients, are also a consequence of medication
      nonadherence and clinical inertia. Poor medication-taking behavior is usually
      defined as medication nonadherence and is responsible for uncontrolled hemoglobin
      A1c level in 23% of cases. Medication nonadherence may also affect clinical
      outcomes, as diabetic patients with good adherence (>=80%) had a significant 10%
      lower rate of hospitalization events and a significant 28% lower rate of all
      cause mortality when compared with patients with poor adherence (<80%). Residual
      vascular risk may be defined as the risk of macrovascular (major cardiovascular
      events) and microvascular (retinopathy, nephropathy, neuropathy) complications
      that remains after intensive and successful glycemic control in type 2 diabetes.
      For major cardiovascular events, risk reduction following intensive glycemic
      control is 9% and, therefore, residual vascular risk is 91%. For microvascular
      complications, as nephropathy, residual vascular risk is as high as 80%. Residual
      vascular risk remains high in type 2 diabetes despite intensive glycemic control.
      Medication nonadherence by the diabetic patient and clinical inertia by the
      clinician may have contributed to the high level of residual vascular risk (both
      macro and microvascular) of type 2 diabetic patients.

PMID- 29322302
TI  - The Superiority of Sucrose Cushion Centrifugation to Ultrafiltration and
      PEGylation in Generating High-Titer Lentivirus Particles and Transducing Stem
      Cells with Enhanced Efficiency.
AB  - Viral gene delivery is hailed as a great milestone in gene-based therapeutic
      approaches. The human immunodeficiency virus-derived lentiviral vectors (LVs) are
      advantageous in infecting both dividing and non-dividing cells leading to
      continuous expression of transgenes. A variety of protocols are available for
      concentration of LVs. We primarily generated our internal ribosome entry site
      (IRES)-based LVs. Virus titration and transduction efficiency were compared
      between various strategies that included sucrose cushion centrifugation (SCC),
      protein column ultrafiltration and polyethylene glycol precipitation. Among these
      approaches, SCC resulted in concentration of high-titer EGFP-expressing
      lentivirus (1.4 +/- 0.3 * 109 TU/ml) with the lowest protein impurities. Further,
      we examined transduction strengths of our three methods on two challenging stem
      cells. Both human NT2 and mouse bone marrow-derived mesenchymal stem cells
      demonstrated high transduction using SCC of 65 +/- 2.8 and 49 +/- 0.8%,
      respectively. Finally, lentivirus particles harboring IRES-based transfer vectors
      of specific genes, concentrated by SCC, integrated into host genome. Taken
      together, development of cost-effective and efficient concentration strategies
      such as our SCC method is yet highly demanded to broaden the horizons of
      lentivirus application in clinical and translational research.

PMID- 29322301
TI  - Effects of short-term DHEA intake on hormonal responses in young recreationally
      trained athletes: modulation by gender.
AB  - BACKGROUND: Dehydroepiandrosterone (DHEA) figures on the World Anti-Doping Agency
      list of prohibited substances in sport because it is assumed that athletes expect
      a significant increase in testosterone through DHEA administration. The
      literature on the hormonal effects of DHEA intake nevertheless appears to be very
      scant in healthy young subjects, especially women. PURPOSE: We examined the
      effects of DHEA on adrenal and gonadal hormones, IGF1 and free T3 in healthy
      young male and female recreationally trained volunteers. METHODS: The study
      followed a double-blind, randomized-order crossover design. Lean healthy young
      men (n = 10) and women (n = 11), with all women using oral contraceptives, were
      treated daily with 100 mg of DHEA and placebo for 4 weeks. DHEA, DHEA-sulfate
      (DHEA-S), androstenedione, total testosterone (Tes), dihydrotestosterone (DHT),
      SHBG, estrone, cortisol, IGF1, and free T3 were measured before, in the middle
      and at the end of each treatment, as were blood glucose, liver transaminases and
      lipid status. RESULTS: We observed a significant increase in DHEA, DHEA-S,
      androstenedione, Tes, DHT, and estrone in both men and women in the middle and at
      the end of DHEA treatment, but the increase in Tes was more marked in women (p <
      0.001) than men (p < 0.05). No changes were found in the other parameters,
      irrespective of gender. CONCLUSION: In young athletes, DHEA administration
      induces significant blood hormonal changes, some modulated by gender, which can
      be used as biomarkers of doping.

PMID- 29322303
TI  - Salt tolerance of two perennial grass Brachypodium sylvaticum accessions.
AB  - KEY MESSAGE: We studied the salt stress tolerance of two accessions isolated from
      different areas of the world (Norway and Tunisia) and characterized the
      mechanism(s) regulating salt stress in Brachypodium sylvaticum Osl1 and Ain1.
      Perennial grasses are widely grown in different parts of the world as an
      important feedstock for renewable energy. Their perennial nature that reduces
      management practices and use of energy and agrochemicals give these biomass crops
      advantages when dealing with modern agriculture challenges such as soil erosion,
      increase in salinized marginal lands and the runoff of nutrients. Brachypodium
      sylvaticum is a perennial grass that was recently suggested as a suitable model
      for the study of biomass plant production and renewable energy. However, its
      plasticity to abiotic stress is not yet clear. We studied the salt stress
      tolerance of two accessions isolated from different areas of the world and
      characterized the mechanism(s) regulating salt stress in B. sylvaticum Osl1,
      originated from Oslo, Norway and Ain1, originated from Ain-Durham, Tunisia. Osl1
      limited sodium transport from root to shoot, maintaining a better K/Na
      homeostasis and preventing toxicity damage in the shoot. This was accompanied by
      higher expression of HKT8 and SOS1 transporters in Osl1 as compared to Ain1. In
      addition, Osl1 salt tolerance was accompanied by higher abundance of the vacuolar
      proton pump pyrophosphatase and Na+/H+ antiporters (NHXs) leading to a better
      vacuolar pH homeostasis, efficient compartmentation of Na+ in the root vacuoles
      and salt tolerance. Although preliminary, our results further support previous
      results highlighting the role of Na+ transport systems in plant salt tolerance.
      The identification of salt tolerant and sensitive B. sylvaticum accessions can
      provide an experimental system for the study of the mechanisms and regulatory
      networks associated with stress tolerance in perennials grass.

PMID- 29322305
TI  - Construction of mammographic examination process ontology using bottom-up
      hierarchical task analysis.
AB  - Describing complex mammography examination processes is important for improving
      the quality of mammograms. It is often difficult for experienced radiologic
      technologists to explain the process because their techniques depend on their
      experience and intuition. In our previous study, we analyzed the process using a
      new bottom-up hierarchical task analysis and identified key components of the
      process. Leveraging the results of the previous study, the purpose of this study
      was to construct a mammographic examination process ontology to formally describe
      the relationships between the process and image evaluation criteria to improve
      the quality of mammograms. First, we identified and created root classes: task,
      plan, and clinical image evaluation (CIE). Second, we described an "is-a"
      relation referring to the result of the previous study and the structure of the
      CIE. Third, the procedural steps in the ontology were described using the new
      properties: "isPerformedBefore," "isPerformedAfter," and
      "isPerformedAfterIfNecessary." Finally, the relationships between tasks and CIEs
      were described using the "isAffectedBy" property to represent the influence of
      the process on image quality. In total, there were 219 classes in the ontology.
      By introducing new properties related to the process flow, a sophisticated
      mammography examination process could be visualized. In relationships between
      tasks and CIEs, it became clear that the tasks affecting the evaluation criteria
      related to positioning were greater in number than those for image quality. We
      developed a mammographic examination process ontology that makes knowledge
      explicit for a comprehensive mammography process. Our research will support
      education and help promote knowledge sharing about mammography examination
      expertise.

PMID- 29322307
TI  - A Psychiatry Resident's Perspective of the "Virtual Preceptor" as an Electronic
      Medical Record Clinical Education Support Tool.

PMID- 29322308
TI  - Quality of Life of Patients with Type 1 Diabetes Mellitus Using Insulin Analog
      Glargine Compared with NPH Insulin: A Systematic Review and Policy Implications.
AB  - INTRODUCTION: Insulin analog glargine (GLA) has been available as one of the
      therapeutic options for patients with type 1 diabetes mellitus to enhance
      glycemic control. Studies have shown that a decrease in the frequency of
      hypoglycemic episodes improves the quality of life (QoL) of diabetic patients.
      However, there are appreciable acquisition cost differences between different
      insulins. Consequently, there is a need to assess their impact on QoL to provide
      future guidance to health authorities. METHOD: A systematic review of multiple
      databases including Medline, LILACS, Cochrane, and EMBASE databases with several
      combinations of agreed terms involving randomized controlled trials and cohorts,
      as well as manual searches and gray literature, was undertaken. The primary
      outcome measure was a change in QoL. The quality of the studies and the risk of
      bias was also assessed. RESULTS: Eight studies were eventually included in the
      systematic review out of 634 publications. Eight different QoL instruments were
      used (two generic, two mixed, and four specific), in which the Diabetes Treatment
      Satisfaction Questionnaire (DTSQ) was the most used. The systematic review did
      not consistently show any significant difference overall in QoL scores, whether
      as part of subsets or combined into a single score, with the use of GLA versus
      neutral protamine Hagedorn (NPH) insulin. Only in patient satisfaction measured
      by DTSQ was a better result consistently seen with GLA versus NPH insulin, but
      not using the Well-being Inquiry for Diabetics (WED) scale. However, none of the
      cohort studies scored a maximum on the Newcastle-Ottawa scale for quality, and
      they generally were of moderate quality with bias in the studies. CONCLUSION:
      There was no consistent difference in QoL or patient-reported outcomes when the
      findings from the eight studies were collated. In view of this, we believe the
      current price differential between GLA and NPH insulin in Brazil cannot be
      justified by these findings.

PMID- 29322309
TI  - The Global Spine Care Initiative: a summary of guidelines on invasive
      interventions for the management of persistent and disabling spinal pain in low-
      and middle-income communities.
AB  - PURPOSE: The purpose of this study was to synthesize recommendations on the use
      of common elective surgical and interventional procedures for individuals with
      persistent and disabling non-radicular/axial with or without myelopathy,
      radicular back pain, cervical myelopathy, symptomatic spinal stenosis, and
      fractures due to osteoporosis. This review was to inform a clinical care pathway
      on the patient presentations where surgical interventions could reasonably be
      considered. METHODS: We synthesized recommendations from six evidence-based
      clinical practice guidelines and one appropriate use criteria guidance for the
      surgical and interventional management of persistent and disabling spine pain.
      RESULTS: Lower priority surgery/conditions include fusion for lumbar/non
      radicular neck pain and higher priority surgery/conditions include
      discectomy/decompressive surgery for cervical or lumbar radiculopathy, cervical
      myelopathy, and lumbar spinal stenosis. Epidural steroid injections are less
      expensive than most surgeries with fewer harms; however, benefits are small and
      short lived. Vertebroplasty should be considered over kyphoplasty as an option
      for patients with severe pain and disability due to osteoporotic vertebral
      compression fracture. CONCLUSION: Elective surgery and interventional procedures
      could be limited in medically underserved areas and low- and middle-income
      countries due to a lack of resources and surgeons and thus surgical and
      interventional procedures should be prioritized within these settings. There are
      non-invasive alternatives that produce similar outcomes and are a recommended
      option where surgical procedures are not available. These slides can be retrieved
      under Electronic Supplementary Material.

PMID- 29322310
TI  - Relationship between sagittal spinal curves geometry and isokinetic trunk muscle
      strength in adults.
AB  - PURPOSE: Sagittal spinal deviation has been reported to be a significant
      musculoskeletal problem affecting both genders and could develop at any age.
      Factors triggering this issue are still not well defined. The purpose of this
      study was to investigate the relationship between sagittal spine angles and
      isokinetic peak, average torque, and power of trunk muscles in asymptomatic
      adults. METHODS: A convenient sample of 79 subjects with asymptomatic spine
      participated in this study. Thoracic and lumbar curves angles were measured using
      the Formetric 4D device. Thoracolumbar (T/L) ratio was calculated as an indicator
      of spine balance. Isokinetic peak and average torque and average power for trunk
      flexors and extensors were measured at 60 degrees /s in seated and semi-standing
      test positions. RESULTS: Lumbar curve angle was moderately inversely correlated
      (p < 0.001) with peak extension torque (rho = - 0.532 and - 0.495 in seated and
      semi-standing positions, respectively) and peak flexion torque (rho = - 0.604 and
      - 0.542 in seated and semi-standing positions, respectively). The T/L ratio was
      found to be significantly associated (p < 0.001) with trunk extension torque (rho
      = 0.422 and 0.378 in seated and semi-standing positions, respectively) and trunk
      flexion torque (rho = 0.396 and 0.321 in seated and semi-standing positions,
      respectively). Similarly, average torque and power measurements were
      significantly correlated with lumbar curve angle and T/L ratio. CONCLUSIONS:
      Sagittal spine balance is associated with trunk muscles strength in adults,
      particularly, the lumbar spine muscles. Therefore, assessment of sagittal spinal
      balance and trunk muscles strength should be taken into consideration when
      designing rehabilitation programs for correction of sagittal spine curvature.

PMID- 29322304
TI  - Causative Genes in Amyotrophic Lateral Sclerosis and Protein Degradation
      Pathways: a Link to Neurodegeneration.
AB  - Amyotrophic lateral sclerosis (ALS) is a disease caused by the degeneration of
      motor neurons (MNs) leading to progressive muscle weakness and atrophy. Several
      molecular pathways have been implicated, such as glutamate-mediated
      excitotoxicity, defects in cytoskeletal dynamics and axonal transport, disruption
      of RNA metabolism, and impairments in proteostasis. ALS is associated with
      protein accumulation in the cytoplasm of cells undergoing neurodegeneration,
      which is a hallmark of the disease. In this review, we focus on mechanisms of
      proteostasis, particularly protein degradation, and discuss how they are related
      to the genetics of ALS. Indeed, the genetic bases of the disease with the
      implication of more than 30 genes associated with familial ALS to date, together
      with the important increase in understanding of endoplasmic reticulum (ER)
      stress, proteasomal degradation, and autophagy, allow researchers to better
      understand the mechanisms underlying the selective death of motor neurons in ALS.
      It is clear that defects in proteostasis are involved in this type of cellular
      degeneration, but whether or not these mechanisms are primary causes or merely
      consequential remains to be clearly demonstrated. Novel cellular and animal
      models allowing chronic expression of mutant proteins, for example, are required.
      Further studies linking genetic discoveries in ALS to mechanisms of protein
      clearance will certainly be crucial in order to accelerate translational and
      clinical research towards new therapeutic targets and strategies.

PMID- 29322311
TI  - Minimally invasive transforaminal lumbar interbody fusion with unilateral pedicle
      screw fixation (UNILIF): morbidity, clinical and radiological 2-year outcomes of
      a 66-patient prospective series.
AB  - PURPOSE: To assess clinical and radiological outcomes at 2-year follow-up of one
      level minimally invasive transforaminal interbody fusion with unilateral pedicle
      screw fixation (UNILIF) in the treatment of stable lumbar degenerative diseases.
      METHODS: From January 1, 2012 to January 31, 2013, we prospectively collected
      clinical and radiological data on patients with stable degenerative lumbar
      disease managed by UNILIF in a single institution. Preoperatively and at 2 years,
      we recorded ODI, SF-12, Quebec and VAS. Interbody fusion was analyzed on
      radiography and on a CT scan, and sagittal balance was tested on full spine
      radiography. RESULTS: Mean operation time was 74.5 min +/- 16.8, mean blood loss
      was 130.8 ml +/- 210.9. At 2 years, ODI, SF-12, Quebec and VAS were significantly
      improved (p > 0.005).The fusion rate was 96.8% on radiographic analysis and was
      87.9% on CT scan analysis. CONCLUSIONS: One-level UNILIF constitutes an effective
      alternative for management of stable lumbar degenerative diseases. These slides
      can be retrieved under Electronic Supplementary Material.

PMID- 29322312
TI  - Assessment of curve progression on children with idiopathic scoliosis using
      ultrasound imaging method.
AB  - PURPOSE: To investigate the threshold of the curve difference on ultrasound
      measurement relative to the previous radiographic measurements to detect curves
      progression in children who have idiopathic scoliosis (IS). METHODS: Two hundred
      children with IS (F:170, M:30; mean age: 14.6 +/- 1.9) were recruited from a
      single center. A retrospective study on comparing the current ultrasound
      measurements with the previous radiographic measurements with threshold values
      from 3 degrees  to 8 degrees  to detect curve progression was conducted. The
      receiver operating characteristic (ROC) analysis, accuracy (ACC), and odd ratio
      (OR) were calculated to determine the optimal threshold value of the curve
      differences between ultrasound and previous radiographic measurement. RESULTS:
      Both thresholds of 4 degrees  and 5 degrees  for curve difference from ultrasound
      scans presented the sensitivities >= 0.90 and specificities >= 0.85, and can
      reduce by 73 and 79% of radiographs on the studied subjects, respectively.
      Especially, for 4 degrees  threshold, the negative likelihood ratio (LR-) was
      only 0.08, which indicated that there is only 8% probability that the subject has
      progressed if the US measurement detected non-progression. CONCLUSIONS: The
      ultrasound imaging method can be applied to identify curve progression in
      children with IS. Four degree is the preferred threshold value to detect the
      curve which had progressed, since it also had the lower rate of undetected
      progressed cases (false negatives).

PMID- 29322314
TI  - Cognitive impairment is associated with elevated serum homocysteine levels among
      older adults.
AB  - PURPOSE: The aim of this study was to examine the associations between the risk
      of cognitive impairment and the serum levels of folate, vitamin B12, and
      homocysteine (Hcy). METHODS: Subjects were persons aged 60-79 years who
      participated in the Yangpyeong Cohort study between 2011 and 2012. Cognitive
      impairment and normal subjects consisted of 100 pairs of old adults matched by
      age, sex, and education levels. Cognitive function was evaluated with the Korean
      version of the Mini-Mental State Examination for Dementia Screening (MMSE-DS).
      Pearson's partial correlation coefficients and conditional multiple logistic
      regression analysis were applied to determine the associations between cognitive
      function and the serum levels of folate, vitamin B12, and Hcy. RESULTS: Compared
      with the matched normal group, the cognitive impairment group had higher
      proportions of folate deficiency (< 3 ng/mL) and hyperhomocysteinemia (>= 15
      umol/L). Serum Hcy concentrations were inversely associated with serum folate (r
      = - 0.234, p = 0.001) and MMSE-DS score (r = - 0.150, p = 0.037) after adjusting
      for age, sex, and education. The high Hcy group showed a higher prevalence of
      cognitive impairment (4th vs. 1st quartile, OR 3.30, 95% CI 1.12-9.72, p for
      trend = 0.014) after adjusting for exercise. CONCLUSIONS: The present findings
      suggest a putative protective role of high serum folate and normal Hcy against
      cognitive impairment among older adults.

PMID- 29322313
TI  - Implantation of an empty polyetheretherketone cage in anterior cervical
      discectomy and fusion: a prospective randomised controlled study with 2 years
      follow-up.
AB  - PURPOSE: To compare the clinical outcomes, radiographic results and fusion rate
      of ACDF between empty PEEK cages and PEEK cages packed with beta-tricalcium
      phosphate. METHODS: Forty-five patients were prospectively enrolled with cervical
      degenerative disc disease who requiring ACDF with a PEEK cage. 23 patients were
      randomised to the study group (empty cages) and 22 patients were in the control
      group (cages filled with beta-tricalcium phosphate). Both patient groups were
      fixed with a cervical locking plate. A CT scan was performed 12 months
      postoperatively and 24 months if not confirmed fused at 12 months to evaluate the
      status of fusion. Clinical status was evaluated using the Japanese Orthopaedic
      Association (JOA) score, the Oswestry Disability Index (ODI) and the Visual
      Analogue Scale (VAS). RESULTS: 46 levels (97.88%) in the study group and 44
      levels (97.77%) in the control group were confirmed as fused at 24 months. There
      was no significant difference between the fusion rates observed in the study and
      control groups (p = 0.82). There was no significant difference in JOA, ODI, or
      VAS scores at 24 months follow-up. The results showed that the members of the non
      fusion group tended to be older than the individuals in the fusion group at 12
      months, but was not significant in statistics. CONCLUSIONS: Similar fusion rates
      and clinical outcomes were achieved when using ACDF with PEEK cages and
      instrumentation, regardless of whether the cage was filled with bone substitute
      at 24 months follow-up. Fusion rates improved over time and are comparable
      between both groups. These slides can be retrieved under Electronic Supplementary
      material.

PMID- 29322315
TI  - Effects of a casein hydrolysate versus intact casein on gastric emptying and
      amino acid responses.
AB  - PURPOSE: Milk proteins and/or their hydrolysates have been reported to have
      beneficial effects for improving postprandial glycaemia. Gastric emptying is a
      major determinant of postprandial glycaemia, yet limited studies have examined
      the effects of intact milk proteins compared to hydrolysates on gastric emptying.
      We investigated gastric emptying of a casein hydrolysate compared to intact
      casein. METHODS: Nine overweight and obese adults (mean +/- SD age: 59.5 +/- 6.5
      years and BMI 28.4 +/- 2.6 kg/m2) were studied in a randomised crossover design.
      Gastric emptying was assessed by paracetamol absorption test, with HPLC-MS being
      used for determining paracetamol and its primary metabolites in plasma. Glucose,
      insulin and amino acid responses were also assessed. RESULTS: Linear mixed model
      analysis showed no effect of treatment [F(1, 55) = 2.1, P = 0.16] or treatment *
      time interactions [F(6, 54) = 1.5, P = 0.21] for paracetamol concentrations. In
      addition, there were no significant differences between the intact casein and
      hydrolysate for any of the gastric emptying outcome measures (Cmax, AUC0-30min,
      AUC0-60min; AUC0-240min). However, insulin was increased in the early
      postprandial period (iAUC0-15min, iAUC0-30min; P < 0.05) and there was a
      treatment effect for glucose [F(1, 53) = 5.3, P = 0.03] following the casein
      hydrolysate compared to intact casein. No significant differences in amino acids
      were found between the two conditions. CONCLUSIONS: Gastric emptying of a casein
      hydrolysate compared to intact casein does not differ. Mechanisms other than
      gastric emptying, for example the presence of a bioactive peptide sequence, may
      contribute to the glycaemic management effects of certain milk protein
      hydrolysates and warrant further investigation.

PMID- 29322316
TI  - Intentional binding of visual effects.
AB  - When an action produces an effect, the effect is perceived earlier in time
      compared to a stimulus without preceding action. This temporal bias is called
      intentional binding (IB) and serves as an implicit measure of sense of agency.
      Typically, IB is investigated by presenting a rotating clock hand while
      participants execute an action and perceive a resulting tone. Participants are
      asked to estimate the time point of tone onset by referring to the clock hand
      position. This time point estimate is compared to a time point estimate of a tone
      in a condition in which the tone occurs without preceding action. Studies
      employing this classic clock paradigm employed auditory action effects. We
      modified this paradigm to investigate potential IB of visual action effects, and,
      additionally, to investigate how IB differs for visual action effects (Experiment
      1) in comparison to auditory action effects (Experiment 2). Our results show
      that, like the IB of an auditory effect, the time point of a visual action effect
      is shifted toward the causing action, and that the size of the IB depends on the
      delay duration of the effect. Comparable to auditory action effects, earlier
      action effects showed stronger IB compared to later action effects. Yet overall
      IB of the visual effects was weaker than IB of the auditory effects. As IB is
      seen as an indicator of sense of agency, this may have important implications for
      the design of human-machine interfaces.

PMID- 29322317
TI  - Probabilistic versus "Pure" Volitional Orienting: a Monocular Difference.
AB  - Human volitional orienting is typically assessed using Posner's endogenous cuing
      task. As a volitional process, the literature has long emphasized the role of
      neocortical structures in this higher cognitive function. Based on recent data,
      we explored the possibility that subcortical channels may have a functional role
      in volitional orienting as measured by a Posner cuing task in which a nonspatial
      feature of a centrally presented cue is predictively related to the location of
      the target. In addition, we have compared this typical cuing task to a "purer"
      version, which does not involve the probability manipulation. A sensitive
      behavioral method was used to probe the contribution of monocular channels
      (mostly subcortical) in the two types of endogenous orienting tasks. In both
      tasks, a spatially informative cue and its ensuing target were presented to the
      same or different eyes at varying cue-target intervals. In the typically used
      endogenous task, the onset of facilitation was apparent earlier when the cue and
      target were presented to the same eye. In contrast, in the "pure" task no
      difference was found between the two eye-of-origin conditions. These data support
      the notion that endogenous facilitation, as measured in the typical Posner cuing
      task, involves lower monocular regions. Hence, in the typical endogenous task,
      which was developed to explore "volitional" orienting, a simple associative
      learning mechanism might elicit monocular, rapid orienting responses. Notably,
      the typical volitional orienting paradigm might be contaminated by simple
      contingency benefits and thus may not provide a pure measure of volitional
      processes.

PMID- 29322318
TI  - Total knee arthroplasty with unexplained pain: new insights from kinematics.
AB  - INTRODUCTION: Up to 20% of total knee arthroplasty patients remain unsatisfied
      post-surgery, and a large proportion of them report anterior knee pain. This
      study aims to verify whether patients who experience anterior knee pain after
      total knee arthroplasty (TKA) will exhibit kinematic characteristics similar to
      those associated with patellofemoral syndrome, including in the frontal and
      transverse planes. MATERIALS AND METHODS: Using four different assessment methods
      [radiological, patient-reported outcome, musculoskeletal assessment with
      functional performance testing, and a 3D kinematic assessment during gait], the
      clinical and 3D knee kinematic profiles of three groups were compared: a painful
      and an asymptomatic TKA group and a healthy control group. All three groups
      underwent a three-dimensional kinematic knee assessment while walking on a
      treadmill. Prosthetic component rotation was assessed through a CT scan
      measurement performed by one experienced radiologist. Flexion/extension,
      ab/adduction, and tibial internal rotation curves were compared, and significant
      differences were highlighted through ANCOVA analysis performed on SPSS. RESULTS:
      A total of 62 knees were evaluated, 24 asymptomatic, 21 painful, and 17 control.
      A dynamic flexion contracture during gait was observed in the painful group,
      which was associated with a lack of flexibility of the thigh muscles. Moreover,
      painful TKA cases exhibited a valgus alignment (- 1.5 degrees ) during stance,
      which increases the Q angle and lateralizes the patella. Finally, CT scan
      evaluation of painful total knee arthroplasty patients revealed that their
      combined components rotation was in slight internal rotation (- 1.4 degrees , SD
      7.0 degrees ). CONCLUSIONS: Painful TKA patients presented three well-known
      characteristics that tend to increase patellofemoral forces and that could be the
      cause of the unexplained pain: a stiff knee gait, a valgus alignment when
      walking, and combined TKA components slightly internally rotated.

PMID- 29322319
TI  - Intraoperative three-dimensional imaging in the treatment of distal radius
      fractures.
AB  - INTRODUCTION: In operative treatment of distal radius fractures satisfying
      outcome mainly relies on anatomical fracture reduction and correct implant
      placement. Examination with two-dimensional fluoroscopy may not provide reliable
      information about this. The aim of this study was to determine the effectiveness
      of additional intraoperative three-dimensional imaging in the operative treatment
      of comminuted distal radius fractures. MATERIALS AND METHODS: From August 2001 to
      June 2015, patients with a distal radius fracture who were treated operatively
      and received intraoperative three-dimensional scan were included. The findings of
      the three-dimensional scan were documented by the operative surgeon and analyzed
      retrospectively with regard to incidence and the need for intraoperative
      revisions. Clinical evaluation included the patient's medical history, the injury
      pattern of the affected wrist (according to the OTA/AO fracture classification)
      and concomitant injuries. Intraoperative and postoperative complications and
      revision surgeries were evaluated as well. RESULTS: Of 4515 operatively treated
      distal radius fractures, 307 (6.8%) received additional intraoperative three
      dimensional imaging during surgery. 263 of 307 patients (85.7%) had a distal
      radius fracture type C. Intraoperative three-dimensional imaging revealed
      findings in 125 patients (40.7%) that were not detected on conventional two
      dimensional fluoroscopy. In 54 patients (17.6%) these findings led to an
      immediate revision. Most commonly, revision was done in the case of remaining
      steps in the articular surface >= 1 mm (n = 25, 8.1%) followed by intra-articular
      screw placement (n = 23, 7.5%). CONCLUSIONS: Intraoperative three-dimensional
      imaging can provide additional information compared to conventional two
      dimensional fluoroscopy in the operative treatment of distal radius fractures
      with the possibility of immediate intraoperative revision.

PMID- 29322320
TI  - Is there a relationship between the load distribution on the tibial plateau and
      hip knee ankle angle after TKA?
AB  - INTRODUCTION: This study asked whether differences in coronal alignment after
      total knee arthroplasty (TKA) affect the load distribution on the tibial plateau.
      The aim of this study was to investigate the correlation between coronal
      alignment and the load distribution on the tibial plateau after TKA, using three
      dimensional multi-detector-row-computed tomography (3D-MDCT). MATERIALS AND
      METHODS: In this study, we performed 84 cementless TKA with porous tantalum
      modular tibial component (PTMT) and divided into three groups based on post
      operative hip-knee-ankle (HKA) angle: varus alignment group (n = 22), (176
      degrees  ?) neutral alignment group (n = 45), (180 degrees  +/- 3 degrees ), and
      valgus alignment group (n = 17) (184 degrees  ?).The changes in bone quality
      parameters of trabecular patterns under peg of PTMT were interpreted as load
      distribution due to changes in alignment. The relationship between HKA angle and
      load distribution on the tibial plateau was analyzed every 6 months for 4.5 years
      by measuring Bone marrow contents/tissue volumes (mg/cm3) and bone volumes/tissue
      volumes (%) under peg of porous tantalum modular tibial component by visualizing
      three dimensionally with 3D-osteo-morphometry software. RESULTS: There were no
      correlations between HKA angle and the load distribution on the tibial plateau
      after TKA at all periods. There was a significantly higher increase in the medial
      region than the lateral about the BMC/TV and BV/TV values, regardless of the post
      operative alignment after TKA for all periods. The relative BMC/TV and BV/TV
      changes at medial region in varus alignment group were significantly lower than
      the neutral and the valgus alignment groups of pre-operative medial
      osteoarthritis of the knee. CONCLUSIONS: As far, it can be concluded by the study
      and the methods used therein that there were no relationships between the load
      distribution on the tibial plateau and HKA angle after TKA. LEVEL OF EVIDENCE:
      Therapeutic study, Level III.

PMID- 29322321
TI  - Polyphagy by omnivory: scavenging improves performance of a polyphagous
      caterpillar on marginal hosts.
AB  - Few species of insect herbivores are highly polyphagous, but those few species
      are disproportionately ecologically and economically important and include many
      of the most destructive crop pests. Common correlates of extreme polyphagy across
      insects include the related behaviors of cannibalism and omnivory, though any
      functional consequences of these behaviors on the host range are unknown. I
      hypothesized that omnivory may allow these insects to exploit marginal hosts
      successfully (an expansion of realized niche). Using the polyphagous pest
      caterpillar, Heliothis virescens, I tested the polyphagy by omnivory hypothesis
      using ten host plants of varying suitability and small quantities of insect
      carrion. Caterpillars which were allowed omnivory had increased performance on
      lower-quality hosts; this treatment raised survival, growth rate, and pupal mass
      over controls on a strictly plant diet. Omnivory allowed successful development
      on two plants that caterpillars could not exploit alone a potential niche
      expansion. This effect was limited, however: (1) on high-quality hosts, omnivory
      did not improve performance, and (2) omnivory on poor hosts did not increase
      growth rate or pupal mass to levels matching the most suitable hosts and it could
      not permit exploitation of a completely unpalatable plant. Omnivory may therefore
      be an important (and overlooked) factor in determining the success of generalist
      insect herbivores in a variety of ecological settings.

PMID- 29322322
TI  - Functional traits can improve our understanding of niche- and dispersal-based
      processes.
AB  - Ecologists often determine the relative importance of niche- and dispersal-based
      processes via variation partitioning based on species composition. Functional
      traits and their proxies of phylogeny are expected to increase the detection of
      niche-based processes and reduce the unexplained variation relative to species
      identity. We collected eight adult tree traits and phylogenetic data of 41
      species and employed a phylogenetic fuzzy weighting method to address this issue
      in a 9-ha temperate forest dynamics plot. We used redundancy analysis to relate
      species, phylogenetic and functional compositions to environmental (soil
      resources and topography) and spatial variables. We also performed multi-scaled
      analyses on spatial variables by adding environment as the covariates to
      determine if functional traits increase the detection of niche-based processes at
      broad scales. The functional traits and intraspecific variation of the wood
      density among ontogenetic stages could dramatically increase the detection of
      niche-based processes and reduce the unexplained variation relative to species
      identity. Phylogenetic and functional compositions were mainly driven by total
      soil P and elevation, while species composition was weakly affected by multiple
      environmental variables. After controlling for the environment, a larger amount
      of the compositional variations in seed mass and maximum height were explained by
      finer-scaled spatial variables, indicating that dispersal processes may be
      important at fine spatial scales. Our results suggested that considering
      functional traits and their intraspecific variations could improve our
      understanding of ecological processes and increase our ability to predict the
      responses of plants to environmental change.

PMID- 29322323
TI  - Arbuscular mycorrhizal fungi and associated microbial communities from dry
      grassland do not improve plant growth on abandoned field soil.
AB  - After abandonment of agricultural fields, some grassland plant species colonize
      these sites with a frequency equivalent to dry grasslands (generalists) while
      others are missing or underrepresented in abandoned fields (specialists). We
      aimed to understand the inability of specialists to spread on abandoned fields by
      exploring whether performance of generalists and specialists depended on soil
      abiotic and/or biotic legacy. We performed a greenhouse experiment with 12
      species, six specialists and six generalists. The plants were grown in sterile
      soil from dry grassland or abandoned field inoculated with microbial communities
      from one or the other site. Plant growth, abundance of mycorrhizal structures and
      plant response to inoculation were evaluated. We focused on arbuscular
      mycorrhizal fungi (AMF), one of the most important parts of soil communities
      affecting plant performance. The abandoned field soil negatively affected plant
      growth, but positively affected plant response to inoculation. The AMF community
      from both sites differed in infectivity and taxa frequencies. The lower AMF taxa
      frequency in the dry grassland soil suggested a lack of functional
      complementarity. Despite the fact that dry grassland AMF produced more
      arbuscules, the dry grassland inoculum did not improve phosphorus nutrition of
      specialists contrary to the abandoned field inoculum. Inoculum origin did not
      affect phosphorus nutrition of generalists. The lower effectiveness of the dry
      grassland microbial community toward plant performance excludes its inoculation
      in the abandoned field soil as a solution to allow settlement of specialists.
      Still, the distinct response of specialists and generalists to inoculation
      suggested that they differ in AMF responsiveness.

PMID- 29322324
TI  - Molecular mapping of qBK1 WD , a major QTL for bakanae disease resistance in
      rice.
AB  - BACKGROUND: Bakanae or foot rot disease is a prominent disease of rice caused by
      Gibberella fujikuroi. This disease may infect rice plants from the pre-emergence
      stage to the mature stage. In recent years, raising rice seedlings in seed boxes
      for mechanical transplanting has increased the incidence of many seedling
      diseases; only a few rice varieties have been reported to exhibit resistance to
      bakanae disease. In this study, we attempted to identify quantitative trait loci
      (QTLs) conferring bakanae disease resistance from the highly resistant japonica
      variety Wonseadaesoo. RESULTS: A primary QTL study using the genotypes/phenotypes
      of the recombinant inbred lines (RILs) indicated that the locus qBK1 WD
      conferring resistance to bakanae disease from Wonseadaesoo was located in a 1.59
      Mb interval delimited on the physical map between chr01_13542347 (13.54 Mb) and
      chr01_15132528 (15.13 Mb). The log of odds (LOD) score of qBK1 WD was 8.29,
      accounting for 20.2% of the total phenotypic variation. We further identified a
      gene pyramiding effect of two QTLs, qBK WD and previously developed qBK1. The
      mean proportion of healthy plant for 31 F4 RILs that had no resistance genes was
      35.3%, which was similar to that of the susceptible check variety Ilpum. The
      proportion of healthy plants for the lines with only qBK WD or qBK1 was 66.1% and
      55.5%, respectively, which was significantly higher than that of the lines
      without resistance genes and that of Ilpum. The mean proportion of the healthy
      plant for 15 F4 RILs harboring both qBK WD and qBK1 was 80.2%, which was
      significantly higher than that of the lines with only qBK WD or qBK1. CONCLUSION:
      Introducing qBK WD or pyramiding the QTLs qBK WD and qBK1 could provide effective
      tools for breeding rice with bakanae disease resistance. To our knowledge, this
      is the first report on a gene pyramiding effect that provides higher resistance
      against bakanae disease.

PMID- 29322325
TI  - Histochemical evidence of IGF2 mRNA-binding protein 2-mediated regulation of
      osteoclast function and adhesive ability.
AB  - Insulin-like growth factor 2 (IGF2) messenger RNA-binding proteins (IMPs) are a
      family of oncofetal RNA-binding proteins that play important roles in cell
      migration, renewal, and metabolism. IMP2 gene expression may be important in
      determining IGF2 levels and might, thereby, be central to bone metabolism. In our
      present study, IMP2-deficient mice exhibited more immature bone structures,
      characterized by abundant residual cartilage cores; growth plates containing more
      rich cartilage matrix, which was arranged irregularly; and a significantly
      thicker hypertrophic chondrocyte layer in the femoral metaphysis, compared with
      wild-type mice. These abnormalities were associated with profound effects on the
      size and morphology of osteoclasts. Specifically, the osteoclasts exhibited
      various polymorphisms, failed to form resorption lacunae, and were detached from
      the bone surface. Consistent with these findings, IMP2 deficiency reduced the
      expression of two important proteases (cathepsin K and matrix metallopeptidase 9)
      as well as that of C-SRC, a critical regulator of ruffled border formation in
      osteoclasts, indicating impaired osteoclastic activity. IMP2-deficient mice also
      displayed inhibited osteoclast adhesion owing to defects in the CD44-osteopontin
      signaling pathway. In summary, we used IMP2-deficient mice as a model to
      determine whether IMP2 plays a role during bone metabolism. Our results indicate
      that IMP2 deficiency delayed bone remodeling by significantly inhibiting the
      activity of osteoclasts and impairing their adhesion.

PMID- 29322326
TI  - Heparan sulfate accumulation and perlecan/HSPG2 up-regulation in tumour tissue
      predict low relapse-free survival for patients with glioblastoma.
AB  - Glycosaminoglycans are major components of brain extracellular matrix (ECM),
      although heparan sulfate (HS) contribution in brain physiology and carcinogenesis
      remains underinvestigated. This study examined HS content and distribution in
      glioblastoma multiforme (GBM) tissues in the context of potential molecular
      mechanisms underlying its deregulation in brain tumours. Totally, 42 tissue
      samples and paraffin-embedded tissues for 31 patients with different prognosis
      were investigated. HS expression was demonstrated in 50-55% of the GBM tumours by
      immunohistochemistry (IHC), while almost no HS content was detected in the
      surrounding paratumourous brain tissues. Heterogeneous HS distribution in the HS
      positive tumours was more related to the necrosis or glandular-like brain zones
      rather than glioma cells with high or low Ki-67 index. According the Kaplan-Meier
      curves, HS accumulation in glioma cells was associated with low relapse-free
      survival (RS) of the GBM patients (p < 0.05) and was likely to be due to the
      increased transcriptional activity of HSPG core proteins (syndecan-1, 2-3 fold;
      glypican-1, 2,5 fold; perlecan/HSPG2, 13-14 fold). Activation of perlecan/HSPG2
      expression correlated with the patients' survival according Kaplan-Meier (p =
      0.0243) and Cox proportional-hazards regression (HR = 3.1; P(Y) = 0.03) analyses,
      while up-regulation of syndecan-1 and glypican-1 was not associated with the
      patients survival. Taken together, the results indicate that increase of HS
      content and up-regulation of perlecan/HSPG2 expression in glioblastoma tissues
      contribute to tumour development through the transformation of brain
      extracellular matrix into tumour microenvironment, and represent negative
      prognostic factors for glioblastoma progression.

PMID- 29322327
TI  - Combined and sequential liver-kidney transplantation in children.
AB  - Combined and sequential liver-kidney transplantation (CLKT and SLKT) is a
      definitive treatment in children with end-stage organ failure. There are two
      major indications: - terminal insufficiency of both organs, or - need for
      transplanting new liver as a source of lacking enzyme or specific regulator of
      the immune system in a patient with renal failure. A third (uncommon) option is
      secondary end-stage renal failure in liver transplant recipients. These three
      clinical settings use distinct qualification algorithms. The most common
      indications include primary hyperoxaluria type 1 (PH1) and autosomal recessive
      polycystic kidney disease (ARPKD), followed by liver diseases associated with
      occasional kidney failure. Availability of anti-C5a antibody (eculizumab) has
      limited the validity of CLKT in genetic atypical hemolytic uremic syndrome
      (aHUS). The liver coming from the same donor as renal graft (in CLKT) is
      immunologically protective for the kidney and this provides long-term rejection
      free follow-up. No such protection is observed in SLKT, when both organs come
      from different donors, except uncommon cases of living donation of both organs.
      Overall long-term outcome in CLKT in terms of graft survival is good and not
      different from isolated liver or kidney transplantation, however patient survival
      is inferior due to complexity of this procedure.

PMID- 29322329
TI  - In Vitro Validation of a Numerical Simulation of Leaflet Kinematics in a
      Polymeric Aortic Valve Under Physiological Conditions.
AB  - This paper describes a computational method to simulate the non-linear structural
      deformation of a polymeric aortic valve under physiological conditions. Arbitrary
      Lagrangian-Eulerian method is incorporated in the fluid-structure interaction
      simulation, and then validated by comparing the predicted kinematics of the
      valve's leaflets to in vitro measurements on a custom-made polymeric aortic
      valve. The predicted kinematics of the valve's leaflets was in good agreement
      with the experimental results with a maximum error of 15% in a single cardiac
      cycle. The fluid-structure interaction model presented in this study can simulate
      structural behaviour of a stented valve with flexible leaflets, providing insight
      into the haemodynamic performance of a polymeric aortic valve.

PMID- 29322328
TI  - Vaccination titres pre- and post-transplant in paediatric renal transplant
      recipients and the impact of immunosuppressive therapy.
AB  - BACKGROUND: Avoidance of vaccine-preventable infections in paediatric renal
      allograft recipients is of utmost importance. However, the development and
      maintenance of protective vaccination titres may be impaired in this patient
      population owing to their need for immunosuppressive medication. METHODS: In the
      framework of the Cooperative European Paediatric Renal Transplant Initiative
      (CERTAIN), we therefore performed a multi-centre, multi-national study and
      analysed vaccination titres pre- and post-transplant in 155 patients with serial
      titre measurements in comparison with published data in healthy children.
      RESULTS: The percentage of patients with positive vaccination titres before renal
      transplantation (RTx) was low, especially for diphtheria (38.5%, control 75%) and
      pertussis (21.3%, control 96.3%). As few as 58.1% of patients had a hepatitis B
      antibody (HBsAb) titre >100 IU/L before RTx. 38.1% of patients showed a
      vaccination titre loss post-transplant. Patients with an HBsAb titre between 10
      and 100 IU/L before RTx experienced a significantly (p < 0.05) more frequent
      hepatitis B vaccination titre loss post-transplant than patients with an HBsAb
      titre >100 IU/L. The revaccination rate post-transplant was low and revaccination
      failed to induce positive titres in a considerable number of patients (27.3 to
      83.3%). Treatment with rituximab was associated with a significantly increased
      risk of a vaccination titre loss post-transplant (odds ratio 4.26, p = 0.033).
      CONCLUSIONS: These data show a low percentage of patients with positive
      vaccination titres pre-transplant, a low revaccination rate post-transplant with
      limited antibody response, and a high rate of vaccination titre losses.

PMID- 29322330
TI  - Answering letter to remark of Dr's Frank and Fitzgerald.

PMID- 29322331
TI  - Correction to: Magnetic resonance imaging for clinical management of rectal
      cancer: Updated recommendations from the 2016 European Society of
      Gastrointestinal and Abdominal Radiology (ESGAR) consensus meeting.
AB  - The article Magnetic resonance imaging for clinical management of rectal cancer:
      Updated recommendations from the 2016 European Society of Gastrointestinal and
      Abdominal Radiology (ESGAR) consensus meeting, written by [SSS AuthorNames SSS].

PMID- 29322332
TI  - Evaluation of age-dependent morphometrics of the meniscofemoral ligaments in
      reference to the posterior cruciate ligament in routine MRI.
AB  - OBJECTIVES: To quantify the morphological correlation between the posterior
      cruciate ligament (PCL) and the meniscofemoral ligaments (MFLs), to propose
      normal ranges for different age populations, and to define guidelines for correct
      identification and differentiation of MFLs in routine MRI. METHODS: Three hundred
      forty-two subjects were included retrospectively and subdivided into five age
      groups. Morphometrics of the PCL and the MFLs were measured on standard MRI in
      the sagittal, coronal, and axial planes. Student's t test, Mann-Whitney U test,
      and ANOVA and Kruskal-Wallis tests with Bonferroni correction were used for
      comparison. RESULTS: The MFLs did not vary significantly between sexes (p > 0.05)
      or in those older than 10 years (p > 0.05). Longitudinal MFL growth is completed
      before age 11 years, with cross-sectional area (CSA) increasing until age 20. The
      CSA of the PCL was significantly (p = 0.028) larger in knees without a pMFL (Mdn
      = 39.7 mm2) than with a pMFL (Mdn = 35.4 mm2). MFLs were more often detected on
      sagittal than coronal images. CONCLUSIONS: This study describes the morphometric
      relation between the PCL and the MFLs on routine MRI. When reporting imaging
      findings in preparation for arthroscopic knee surgery, evaluation of MFLs, first
      in the sagittal and then the coronal plane, will achieve the best results. KEY
      POINTS: * The MFLs and the PCL have distinct morphological patterns throughout
      life. * These patterns show intimate anatomical relationships and a potential
      biomechanical impact. * Those patterns and relationships can be quantified with
      MRI. * A correlation exists between age and morphometrics of the MFLs. *
      Recommendations for correct identification of the MFLs are provided.

PMID- 29322333
TI  - Whole-body ultra-low dose CT using spectral shaping for detection of osteolytic
      lesion in multiple myeloma.
AB  - OBJECTIVES: The aim of this study was to investigate the radiation dose and image
      quality of a whole-body low-dose CT (WBLDCT) using spectral shaping at 100 kV (Sn
      100 kV) for the assessment of osteolytic lesions in patients with multiple
      myeloma. METHODS: Thirty consecutive patients were retrospectively selected, who
      underwent a WBLDCT on a third-generation dual-source CT (DSCT) (Sn 100 kV, ref.
      mAs: 130). They were matched with patients, who were examined on a second
      generation DSCT with a standard low-dose protocol (100 kV, ref. mAs: 111).
      Objective and subjective image quality, radiation exposure as well as the
      frequency of osteolytic lesions were evaluated. RESULTS: All scans were of
      diagnostic image quality. Subjective overall image quality was significantly
      higher in the study group (p = 0.0003). Objective image analysis revealed that
      signal intensities, signal-to-noise ratio and contrast-to-noise ratio of the bony
      structures were equal or significantly higher in the control group. There was no
      significant difference in the frequency of osteolytic lesions (p = 0.259). The
      median effective dose of the study protocol was significantly lower (1.45 mSv vs.
      5.65 mSv; p < 0.0001). CONCLUSION: WBLDCT with Sn 100 kV can obtain sufficient
      image quality for the depiction of osteolytic lesions while reducing the
      radiation dose by approximately 74%. KEY POINTS: * Spectral shaping using tin
      filtration is beneficial for whole-body low-dose CT * Sn 100 kV yields sufficient
      image quality for depiction of osteolytic lesions * Whole-body low-dose CT can be
      performed with a median dose of 1.5 mSv.

PMID- 29322335
TI  - Mechanobiological modeling of endochondral ossification: an experimental and
      computational analysis.
AB  - Long bone formation starts early during embryonic development through a process
      known as endochondral ossification. This is a highly regulated mechanism that
      involves several mechanical and biochemical factors. Because long bone
      development is an extremely complex process, it is unclear how biochemical
      regulation is affected when dynamic loads are applied, and also how the
      combination of mechanical and biochemical factors affect the shape acquired by
      the bone during early development. In this study, we develop a mechanobiological
      model combining: (1) a reaction-diffusion system to describe the biochemical
      process and (2) a poroelastic model to determine the stresses and fluid flow due
      to loading. We simulate endochondral ossification and the change in long bone
      shapes during embryonic stages. The mathematical model is based on a multiscale
      framework, which consisted in computing the evolution of the negative feedback
      loop between Ihh/PTHrP and the diffusion of VEGF molecule (on the order of days)
      and dynamic loading (on the order of seconds). We compare our morphological
      predictions with the femurs of embryonic mice. The results obtained from the
      model demonstrate that pattern formation of Ihh, PTHrP and VEGF predict the
      development of the main structures within long bones such as the primary
      ossification center, the bone collar, the growth fronts and the cartilaginous
      epiphysis. Additionally, our results suggest high load pressures and frequencies
      alter biochemical diffusion and cartilage formation. Our model incorporates the
      biochemical and mechanical stimuli and their interaction that influence
      endochondral ossification during embryonic growth. The mechanobiochemical
      framework allows us to probe the effects of molecular events and mechanical
      loading on development of bone.

PMID- 29322334
TI  - Detection of beta-lactamase encoding genes in feces, soil and water from a
      Brazilian pig farm.
AB  - beta-lactam antibiotics are widely used for the treatment of different types of
      infections worldwide and the resistance to these antibiotics has grown sharply,
      which is of great concern. Resistance to beta-lactams in gram-negative bacteria
      is mainly due to the production of beta-lactamases, which are classified
      according to their functional activities. The aim of this study was to verify the
      presence of beta-lactamases encoding genes in feces, soil, and water from a
      Brazilian pig farm. Different beta-lactamases encoding genes were found,
      including blaCTX-M-Gp1, blaCTX-M-Gp9, blaSHV, blaOXA-1-like, blaGES, and blaVEB.
      The blaSHV and blaCTX-M-Gp1 genes have been detected in all types of samples,
      indicating the spread of beta-lactam resistant bacteria among farm pigs and the
      environment around them. These results indicate that beta-lactamase encoding
      genes belonging to the cloxacillinase, ESBL, and carbapenemase and they have high
      potential to spread in different sources, due to the fact that genes are closely
      related to mobile genetic elements, especially plasmids.

PMID- 29322336
TI  - Correction to: Meta-analysis of adjunctive dexamethasone to improve clinical
      outcome of bacterial meningitis in children.
AB  - The original version of this article unfortunately contained an error.

PMID- 29322337
TI  - IVH scoring system.

PMID- 29322338
TI  - The oscillatory flow of the cerebrospinal fluid in the Sylvian aqueduct and the
      prepontine cistern measured with phase contrast MRI in children with
      hydrocephalus-a preliminary report.
AB  - INTRODUCTION: Recognizing patients with ventriculomegaly who are at risk of
      developing acute hydrocephalus presents a challenge for the clinician. The
      association between disturbed cerebrospinal fluid flow (CSF) and impaired brain
      compliance may play a role in the pathogenesis of hydrocephalus. Phase contrast
      MRI is a noninvasive technique which can be used to assess CSF parameters. The
      aim of the work is to evaluate the effectiveness of phase contrast MRI in
      recognizing patients at risk of acute hydrocephalus, based on measuring the
      pulsatile CSF flow parameters in the Sylvian aqueduct and prepontine cistern in
      children with ventriculomegaly. AIM: The aim of the work is to characterize the
      parameters of cerebrospinal fluid (CSF) flow in the Sylvian aqueduct and
      prepontine cistern in children with ventriculomegaly with regard to patient age
      and symptoms. We hypothesize that the relationship between CSF flow parameters in
      these two regions will vary according to analyzed factors and it will allow to
      recognize children at risk of hydrocephalus. MATERIALS AND METHODS: A group of 26
      children with ventriculomegaly (five girls and 21 boys) underwent phase contrast
      MRI examinations (Philips 3T Achieva with Q-flow integral application).
      Amplitudes of average and peak velocities of the CSF flow through the Sylvian
      aqueduct and prepontine cistern were used to calculate ratios of oscillation and
      peak velocities, respectively. The relationship between the oscillation
      coefficient, the peak velocity coefficient, and stroke volume was then assessed
      in accordance with age and clinical symptoms. RESULTS: The peak velocity
      coefficient was significantly higher in patients with hyper-oscillating flow
      through the Sylvian aqueduct (3.04 +/- 3.37 vs. 0.54 +/- 0.28; p = 0.0094).
      Moreover, these patients tended to develop symptoms more often (p = 0.0612). No
      significant age-related changes were observed in CSF flow parameters. CONCLUSION:
      Phase contrast MRI is a useful tool for noninvasive assessment of CSF flow
      parameters. The application of coefficients instead of direct values seems to
      better represent hemodynamic conditions in the ventricular system. However,
      further studies are required to evaluate their clinical significance and normal
      limits.

PMID- 29322339
TI  - Dolichoectasia of the anterior cerebral arteries: a rare cause of headache in a
      young child.

PMID- 29322340
TI  - The use of a smartphone-assisted ventricle catheter guide for Ommaya reservoir
      placement-experience of a retrospective bi-center study.
AB  - BACKGROUND: For intraventricular chemotherapy (IVC) as part of many oncological
      treatment protocols, Ommaya reservoir is enabling repeated access to the cerebro
      spinal fluid (CSF). The correct placement of the catheter in the ventricle is
      essential for correct application of drugs, which is enabled by sophisticated
      techniques such as neuronavigation. OBJECTIVE: In a bi-center retrospective
      study, we reviewed our experience using a smartphone-assisted ventricle catheter
      guide as simple solution for correct Ommaya reservoir placement. METHODS: Sixty
      Ommaya reservoirs have been placed in 60 patients between 2011 and 2017 with the
      smartphone-assisted ventricular catheter guidance technique. Patient
      characteristics, preoperative frontal and occipital horn ratio (FOHR),
      postoperative catheter position, and complications were assessed. RESULTS: The
      majority of our patients (71.6%) have got narrow or slit-like ventricles (FOHR <=
      0.4). All Ommaya reservoirs were placed successfully. Fifty-eight ventricular
      catheters (97%) were inserted at the first and 2 (3%) at the second attempt using
      the same technique. No immediate perioperative complications were observed. All
      catheters (100%) could be used for IVC. Postoperative imaging was available in 52
      patients. Thirty-two (61.5%) of ventricular catheters were rated as grade I, 20
      (38.5%) as grade II, and none (0%) as grade III. Four patients (6.7%) showed
      postoperative complications during a median follow-up of 8.5 months
      (hydrocephalus, n = 1; infection, n = 1; parenchymal cyst around catheter, n = 1;
      shunt revision, n = 1). CONCLUSIONS: The smartphone-assisted guide offers decent
      accuracy of ventricle catheter placement with ease and simplicity for a small
      surgical intervention. We propose this technique as routine tool for Ommaya
      reservoir placement independent of lateral ventricular size to decrease the rate
      of ventricle catheter malposition as reasonable alternative to a neuronavigation
      system.

PMID- 29322342
TI  - Alcohol and disease activity in axial spondyloarthritis: a cross-sectional study.
AB  - The objective of this study was to explore associations between alcohol
      consumption and disease activity in axial spondyloarthritis (axSpA). We conducted
      a cross-sectional study of axSpA participants meeting the ASAS criteria.
      Associations between self-reported current alcohol use and disease activity
      (BASDAI, spinal pain, ASDAS), functional impairment (BASFI), and quality of life
      were explored using multivariable linear models, adjusting for age, gender,
      symptom duration, use of TNF inhibition therapy, smoking, deprivation, and
      anxiety and depression (A&D). Within alcohol drinkers, effect of increased
      alcohol intake (defined as > 14 units/week) was explored with moderate drinking
      (<= 14 units/week) as reference. The study cohort comprised 229 axSpA patients
      and 76% were male with mean age 46.5 years (SD +/- 13.8). Alcohol drinking was
      reported by 64%, with a median of 6 units per week among drinkers. Compared with
      non-drinkers, drinkers had lower BASDAI (beta = - 0.83; 95% CI - 1.49, - 0.17),
      ASDAS (beta = - 0.36; 95% CI - 0.66, - 0.05) and BASFI (beta = - 1.40; 95% CI -
      2.12, - 0.68). These associations were in contrast to, and independent of, the
      detrimental effects of smoking, depression, and deprivation. Subgroup analysis in
      alcohol drinkers did not reveal significant associations between disease severity
      and increased alcohol intake. Stratified analyses by smoking revealed that in
      never-smokers without depression, alcohol was associated with greater reduction
      in disease activity: BASDAI (beta = - 1.69; 95% CI - 2.93, - 0.45), ASDAS (beta =
      - 0.60; 95% CI - 1.18, - 0.02). Favourable axSpA disease activity and function
      were observed in association with alcohol consumption in this cross-sectional
      study. Longitudinal study is required to explore whether this relationship is due
      to biological effects of alcohol on disease process or disease-associated
      behaviour modification.

PMID- 29322341
TI  - Interstitial lung disease in systemic sclerosis: data from the spanish
      scleroderma study group.
AB  - OBJECTIVES: To evaluate the clinical characteristics of patients with
      interstitial lung disease (ILD) in the setting of a large cohort of systemic
      sclerosis (SSc) patients, and to analyse the differences according to the SSc
      subtype (following the modification of classification criteria of the American
      College of Rheumatology for SSc proposed by LeRoy and Medsger), factors are
      associated with moderate-to-severe impairment of lung function, as well as
      mortality and causes of death. METHODS: A descriptive study was performed, using
      the available data from the Spanish Scleroderma Study Group. RESULTS: Twenty-one
      referral centers participated in the registry. By April 2014, 1374 patients with
      SSc had been enrolled, and 595 of whom (43%) had ILD: 316 (53%) with limited
      cutaneous SSc (lcSSc), 240 (40%) with diffuse cutaneous SSc (dcSSc), and 39 (7%)
      with SSc sine scleroderma (ssSSc). ILD in the lcSSc and the ssSSc subsets tended
      to develop later, and showed a less impaired forced vital capacity (FVC) and a
      ground glass pattern on high-resolution computed tomography (HRCT) less
      frequently, compared with the dcSSc subset. Factors related to an FVC < 70% of
      predicted in the multivariate analysis were: dcSSc, positivity to anti
      topoisomerase I antibodies, a ground glass pattern on HCRT, an active nailfold
      capillaroscopy pattern, lower DLco, older age at symptoms onset, and longer time
      between symptoms onset and ILD diagnosis. Finally, SSc-associated mortality and
      ILD-related mortality were highest in dcSSc patients, whereas that related to
      pulmonary arterial hypertension was highest in those with lcSSc-associated ILD.
      CONCLUSIONS: Our study indicates that ILD constitutes a remarkable complication
      of SSc with significant morbidity and mortality, which should be borne in mind in
      all three subgroups (lcSSc, dcSSc, and ssSSc).

PMID- 29322343
TI  - Rituximab for anti-neutrophil cytoplasmic antibodies-associated vasculitis:
      experience of a single center and systematic review of non-randomized studies.
AB  - Rituximab (RTX) is becoming a standard treatment for patients with anti
      neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) but
      heterogeneity exists regarding its use. We present our uncontrolled experience
      with RTX in patients with refractory AAV and also the results of a systematic
      review of non-randomized studies on RTX in AAV patients. We retrospectively
      reviewed the records of AAV patients treated with RTX following an inadequate
      response to immunosuppressives between 2011 and 2015. The systematic review
      covered all English articles listed in PubMed until June 2017. There were 25 AAV
      patients (21 GPA, four unclassified) treated with RTX (median 2, IQR 1-3 courses;
      median follow-up 24, IQR 17-50 months). The kidney and the lung were the most
      commonly affected organs, observed in 14 and 16 patients, respectively. Complete
      remission rate was 72% at month 6 and 88% at month 12. Two patients had died and
      three serious adverse events occurred. The systematic review included 56 studies
      on 1422 patients with the majority being on refractory or relapsing disease.
      There was wide variability regarding disease characteristics, endpoints,
      concomitant immunosuppressives and RTX schedule. Most studies reported > 80%
      complete or partial remission rates with the lowest response (37.5%) for
      granulomatous lesions. The relapse rate was 30%. Infections and infusion
      reactions were the main adverse events. Our experience with RTX in refractory AAV
      is in line with the literature in terms of efficacy and safety. The systematic
      review underlines many uncertainties on its optimal use.

PMID- 29322344
TI  - Deadtime effects in quantification of 177Lu activity for radionuclide therapy.
AB  - BACKGROUND: The aim of this study was to investigate the deadtime (DT) effects
      that are present in 177Lu images acquired after radionuclide therapy injection,
      assess differences in DT based on the full spectrum and the photopeak-only
      measurements, and design a method to correct for the deadtime losses. A Siemens
      SymbiaT SPECT/CT camera with a medium energy collimator was used. A 295-mL bottle
      was placed off-center inside a large cylinder filled with water, and 177Lu
      activity was sequentially added up to a maximum of 9.12 GBq. The true count rates
      vs. observed count rates were plotted and fitted to the DT paralyzable model.
      This analysis was performed using counts recorded in the full spectrum and in
      other energy windows. The DT correction factors were calculated using the
      percentage difference between the true and the observed count rates. RESULTS: The
      DT values of 5.99 +/- 0.02 MUs, 4.60 +/- 0.052 MUs, and 0.19 +/- 0.18 MUs were
      obtained for the primary photons (PP) recorded in the 113- and 208-keV photopeaks
      and for the full spectrum, respectively. For the investigated range of count
      rates, the DT correction factors of up to 23% were observed for PP corresponding
      to the 113-keV photopeak, while for the 208-keV photopeak values of up to 20%
      were obtained. These values were almost three times higher than the deadtime
      correction factors derived from the full spectrum. CONCLUSIONS: The paralyzable
      model showed to be appropriate for the investigated range of counts, which were
      five to six times higher than those observed in the patient post-therapy imaging.
      Our results suggest that the deadtime corrections should be based on count losses
      in the scatter-corrected photopeak window and not on the deadtime determined from
      the full spectrum. Finally, a general procedure that can be followed to correct
      patient images for deadtime is presented.

PMID- 29322345
TI  - Freshwater shrimps (Macrobrachium depressimanum and Macrobrachium jelskii) as
      biomonitors of Hg availability in the Madeira River Basin, Western Amazon.
AB  - Total mercury (THg) concentrations measured in two freshwater shrimp species
      (Macrobrachium depressimanum and Macrobrachium jelskii) showed a relationship
      with the location of artisanal and small-scale gold mining (ASGM) from the
      Madeira River Basin, Western Amazon. Between August 2009 and May 2010, 212 shrimp
      samples were collected in the confluence of the Madeira River with three of its
      tributaries (Western Amazon). THg concentration was quantified in the
      exoskeleton, hepatopancreas and muscle tissue of the shrimps by cold vapor atomic
      absorption spectrophotometry. There were no significant differences between the
      two shrimp species when samples came from the Madeira River, but Hg
      concentrations were significantly lower in a tributary outside the influence of
      the gold mining area. Average THg concentrations were higher in the
      hepatopancreas (up to 160.0 ng g-1) and lower in the exoskeleton and muscle
      tissue (10.0-35.0 ng g-1 and < 0.9-42.0 ng g-1, respectively). Freshwater shrimps
      from the Madeira River respond to local environmental levels of Hg and can be
      considered as biomonitors for environmental Hg at this spatial scale. These
      organisms are important for moving Hg up food webs including those that harbor
      economic significant fish species and thus enhancing human exposure.

PMID- 29322347
TI  - All aspect of toxic effect of brilliant blue and sunset yellow in Allium cepa
      roots.
AB  - Substances added to food are considerable for survival and are the oldest
      technologies used in preservation, sweetening and coloring. This work was
      conducted to evaluate the toxicity of the food additives sunset yellow (SY) and
      brilliant blue (BB) on Allium cepa root meristematic cells. Control and treatment
      groups were created from germinated roots. Group 1 (control group) did not
      receive chemicals. Group 2 (SY or BB-treatment group), received increasing doses
      of SY (25, 50, 100 and 500 ppm) and BB (100, 200, 400 and 500 ppm) with time
      periods of 24, 48 and 72 h. After different treatment periods, the roots were
      obtained from all groups and EC50 concentrations, cell death, chromosome
      aberrations, mitotic index were observed by a light microscopy. Changing
      antioxidant capacity of roots was determined by FRAP and TEAC assay. Also, DNA
      damage was measured by comet assay and RAPD-PCR technique. Approximately 50 and
      200 ppm were accepted as EC50 value for SY and BB, respectively. Chromosome
      aberration values were obtained with increasing concentrations and longer
      treatment times such as chromosome bridge, C-mitosis, micronucleus, chromosome
      mis-segregation in both groups. Increasing exposure doses of SY and BB caused
      decreasing mitotic index values at 72 h. FRAP and TEAC assay showed that
      antioxidant capacity of roots was decreased by increasing concentrations of SY
      and BB. The tail DNA% and tail length significantly increased for all exposure
      times when compared to the control group. 50 and 200 ppm of SY and BB caused a
      genotoxic effect on genetic material at 72 h according to RAPD-PCR. Increasing
      the doses of SY and BB resulted in increased toxicity to all studied parameters
      of A. cepa. In conclusion, the SY and BB tested in this study have cytotoxic and
      mutagenic potential. Furthermore, SY is more harmful than BB for use in the A.
      cepa root meristematic cells.

PMID- 29322346
TI  - Study on the incidence and influences on heterotopic pregnancy from embryo
      transfer of fresh cycles and frozen-thawed cycles.
AB  - PURPOSE: The purpose of this study was to determine the heterotopic pregnancy
      rate using fresh versus frozen-thawed embryo transfers and factors associated
      with heterotopic pregnancy (HP). Management and clinical outcomes after
      heterotopic pregnancy were also evaluated. METHODS: In this retrospective cohort
      study, we included 12,484 women who had clinical pregnancies after in vitro
      fertilization treatment at our fertility center between 2012 and 2017. Patients
      received fresh day 3 embryos (F-D3 group), fresh day 5 blastocysts (F-D5 group),
      frozen-thawed day 3 embryos (T-D3 group), or frozen-thawed day 5 or 6 blastocysts
      (T-D5/6 groups) transfers. The primary outcome measure was the occurrence of
      heterotopic pregnancy. Factors associated with heterotopic pregnancy were
      analyzed using logistic regression. RESULTS: The heterotopic pregnancy rates were
      0.58% in the F-D3, 0.39% in F-D5, 0.56% in T-D3, and 0.33% in T-D5/6 groups, but
      no differences were found between groups. The risk factors of HP included a
      history of previous ectopic pregnancy (odds ratio [OR] 5.805, 95% CI 4.578-9.553,
      P = 0.016) and pelvic inflammation diseases (OR 1.129, 95% CI 1.021-3.178, P =
      0.047). Salpingectomy was performed in 62.9% patients either through laparoscopy
      or through laparotomy. The early abortion rate and late abortion rate were 29.03%
      and 1.61%, respectively. In total, 66.13% of the patients had a live birth,
      either a singleton (90.24%) or twins (9.76%). CONCLUSION: No significant
      difference in the incidence of heterotopic pregnancy in fresh IVF cycles vs.
      frozen-thawed cycles could be demonstrated in a large cohort of patients. The
      risk factors of HP included history of ectopic pregnancy and PID. The clinical
      outcome after heterotopic pregnancy appears to be favorable.

PMID- 29322348
TI  - Optimisation of a potency assay for the assessment of immunomodulative potential
      of clinical grade multipotent mesenchymal stromal cells.
AB  - Clinical use of multipotent Mesenchymal Stromal Cell (MSC)-based medicinal
      products requires their production in compliance with Good Manufacturing
      Practices, thus ensuring that the final drug product meets specifications
      consistently from batch to batch in terms of cell viability, identity, purity and
      potency. Potency relates to the efficacy of the medicine in its target clinical
      indication, so adequate release tests need to be defined and validated as quality
      controls. Herein we report the design and optimisation of parameters affecting
      the performance of an in vitro cell-based assay for assessing immunomodulatory
      potential of clinical grade MSC for human use, based on their capacity to inhibit
      proliferation of T lymphocytes under strong polyclonal stimuli. The resulting
      method was demonstrated to be reproducible and relatively simple to execute. Two
      case studies using clinical grade MSC are presented as examples to illustrate the
      applicability of the methodology described in this work.

PMID- 29322349
TI  - Development of a chemically defined platform fed-batch culture media for
      monoclonal antibody-producing CHO cell lines with optimized choline content.
AB  - A chemically defined platform basal medium and feed media were developed using a
      single Chinese hamster ovary (CHO) cell line that produces a monoclonal antibody
      (mAb). Cell line A, which showed a peak viable cell density of 5.9 * 106 cells/mL
      and a final mAb titer of 0.5 g/L in batch culture, was selected for the platform
      media development. Stoichiometrically balanced feed media were developed using
      glucose as an indicator of cell metabolism to determine the feed rates of all
      other nutrients. A fed-batch culture of cell line A using the platform fed-batch
      medium yielded a 6.4 g/L mAb titer, which was 12-fold higher than that of the
      batch culture. To examine the applicability of the platform basal medium and feed
      media, three other cell lines (A16, B, and C) that produce mAbs were cultured
      using the platform fed-batch medium, and they yielded mAb titers of 8.4, 3.3, and
      6.2 g/L, respectively. The peak viable cell densities of the three cell lines
      ranged from 1.3 * 107 to 1.8 * 107 cells/mL. These results show that the
      nutritionally balanced fed-batch medium and feeds worked well for other cell
      lines. During the medium development, we found that choline limitation caused a
      lower cell viability, a lower mAb titer, a higher mAb aggregate content, and a
      higher mannose-5 content. The optimal choline chloride to glucose ratio for the
      CHO cell fed-batch culture was determined. Our platform basal medium and feed
      media will shorten the medium-development time for mAb-producing cell lines.

PMID- 29322350
TI  - Monogenic disorders that mimic the phenotype of Rett syndrome.
AB  - Rett syndrome (RTT) is caused by mutations in methyl-CpG-binding protein 2
      (MECP2), but defects in a handful of other genes (e.g., CDKL5, FOXG1, MEF2C) can
      lead to presentations that resemble, but do not completely mirror, classical RTT.
      In this study, we attempted to identify other monogenic disorders that share
      features with RTT. We performed a retrospective chart review on n = 319 patients
      who had undergone clinical whole exome sequencing (WES) for further etiological
      evaluation of neurodevelopmental diagnoses that remained unexplained despite
      extensive prior workup. From this group, we characterized those who (1) possessed
      features that were compatible with RTT based on clinical judgment, (2)
      subsequently underwent MECP2 sequencing and/or MECP2 deletion/duplication
      analysis with negative results, and (3) ultimately arrived at a diagnosis other
      than RTT with WES. n = 7 patients had clinical features overlapping RTT with
      negative MECP2 analysis but positive WES providing a diagnosis. These seven
      patients collectively possessed pathogenic variants in six different genes: two
      in KCNB1 and one each in FOXG1, IQSEC2, MEIS2, TCF4, and WDR45. n = 2 (both with
      KCNB1 variants) fulfilled criteria for atypical RTT. RTT-associated features
      included the following: loss of hand or language skills (n = 3; IQSEC2, KCNB1 x
      2); disrupted sleep (n = 4; KNCB1, MEIS2, TCF4, WDR45); stereotyped hand
      movements (n = 5; FOXG1, KNCB1 x 2, MEIS2, TCF4); bruxism (n = 3; KCNB1 x 2;
      TCF4); and hypotonia (n = 7). Clinically based diagnoses can be misleading,
      evident by the increasing number of genetic conditions associated with features
      of RTT with negative MECP2 mutations.

PMID- 29322351
TI  - From Pacemaker to Wearable: Techniques for ECG Detection Systems.
AB  - With the alarming rise in the deaths due to cardiovascular diseases (CVD),
      present medical research scenario places notable importance on techniques and
      methods to detect CVDs. As adduced by world health organization, technological
      proceeds in the field of cardiac function assessment have become the nucleus and
      heart of all leading research studies in CVDs in which electrocardiogram (ECG)
      analysis is the most functional and convenient tool used to test the range of
      heart-related irregularities. Most of the approaches present in the literature of
      ECG signal analysis consider noise removal, rhythm-based analysis, and heartbeat
      detection to improve the performance of a cardiac pacemaker. Advancements
      achieved in the field of ECG segments detection and beat classification have a
      limited evaluation and still require clinical approvals. In this paper,
      approaches on techniques to implement on-chip ECG detector for a cardiac
      pacemaker system are discussed. Moreover, different challenges regarding the ECG
      signal morphology analysis deriving from medical literature is extensively
      reviewed. It is found that robustness to noise, wavelet parameter choice,
      numerical efficiency, and detection performance are essential performance
      indicators required by a state-of-the-art ECG detector. Furthermore, many
      algorithms described in the existing literature are not verified using ECG data
      from the standard databases. Some ECG detection algorithms show very high
      detection performance with the total number of detected QRS complexes. However,
      the high detection performance of the algorithm is verified using only a few
      datasets. Finally, gaps in current advancements and testing are identified, and
      the primary challenge remains to be implementing bullseye test for morphology
      analysis evaluation.

PMID- 29322354
TI  - Mutations of key driver genes in colorectal cancer progression and metastasis.
AB  - The association between mutations of key driver genes and colorectal cancer (CRC)
      metastasis has been investigated by many studies. However, the results of these
      studies have been contradictory. Here, we perform a comprehensive analysis to
      screen key driver genes from the TCGA database and validate the roles of these
      mutations in CRC metastasis. Using bioinformatics analysis, we identified six key
      driver genes, namely APC, KRAS, BRAF, PIK3CA, SMAD4 and p53. Through a systematic
      search, 120 articles published by November 30, 2017, were included, which all
      showed roles for these gene mutations in CRC metastasis. A meta-analysis showed
      that KRAS mutations (combined OR 1.18, 95% CI 1.05-1.33) and p53 mutations
      (combined OR 1.49, 95% CI 1.23-1.80) were associated with CRC metastasis,
      including lymphatic and distant metastases. Moreover, CRC patients with a KRAS
      mutation (combined OR 1.29, 95% CI 1.13-1.47), p53 mutation (combined OR 1.35,
      95% CI 1.06-1.72) or SMAD4 mutation (combined OR 2.04, 95% CI 1.41-2.95) were at
      a higher risk of distant metastasis. Subgroup analysis stratified by ethnic
      populations indicated that the BRAF mutation was related to CRC metastasis
      (combined OR 1.42, 95% CI 1.18-1.71) and distant metastasis (combined OR 1.51,
      95% CI 1.20-1.91) in an Asian population. No significant association was found
      between mutations of APC or PIK3CA and CRC metastasis. In conclusion, mutations
      of KRAS, p53, SMAD4 and BRAF play significant roles in CRC metastasis and may be
      both potential biomarkers of CRC metastasis as well as therapeutic targets.

PMID- 29322356
TI  - Inherent health and environmental risk assessment of nanostructured metal oxide
      production processes.
AB  - The health and environmental effects of chemical processes can be assessed during
      the initial stage of their production. In this paper, the Chemical Screening Tool
      for Exposure and Environmental Release (ChemSTEER) software was used to compare
      the health and environmental risks of spray pyrolysis and wet chemical techniques
      for the fabrication of nanostructured metal oxide on a semi-industrial scale with
      a capacity of 300 kg/day in Iran. The pollution sources identified in each
      production process were pairwise compared in Expert Choice software using
      indicators including respiratory damage, skin damage, and environmental damages
      including air, water, and soil pollution. The synthesis of nanostructured zinc
      oxide using the wet chemical technique (with 0.523 wt%) leads to lower health and
      environmental risks compared to when spray pyrolysis is used (with 0.477 wt%).
      The health and environmental risk assessment of nanomaterial production processes
      can help select safer processes, modify the operation conditions, and select or
      modify raw materials that can help eliminate the risks.

PMID- 29322353
TI  - Quercetin exerts cardiovascular protective effects in LPS-induced dysfunction in
      vivo by regulating inflammatory cytokine expression, NF-kappaB phosphorylation,
      and caspase activity.
AB  - Impaired myocardial contractile function, one of the well-documented features of
      sepsis, contributes greatly to the high rate of mortality. Quercetin is widely
      accepted as a potential antioxidant and free radical scavenger. Epidemiologic
      studies have suggested that an increase in the intake of dietary Quercetin can
      reduce the risk of cardiac disease. However, presently there is no report yet on
      the influence of Quercetin on LPS-induced myocardial dysfunction in vivo.
      Cardiovascular protective effects of Quercetin on LPS-induced sepsis in mice were
      measured after intragastric administration, using normal saline as a positive
      control. Quercetin pretreatment significantly alleviated LPS-induced cardiac
      abnormalities in mice. The histopathologic findings in the present study justify
      the findings reported from the biochemical analyses. Our observation from the
      present research work reveals that Quercetin suppressed the production of
      proinflammatory cytokines at different levels, such as TNF-alpha and IL-1beta,
      and inhibits the activation of I-kappaB phosphorylation, whereas the total
      content was not affected. Apoptotic pathways are related to Quercetin protection
      in the development of myocardial dysfunction. In conclusion, our findings
      demonstrate the adjuvant potentials of Quercetin for clinical sepsis treatment.

PMID- 29322352
TI  - Supraclavicular catheterization of the brachiocephalic vein: a way to prevent or
      reduce catheter maintenance-related complications in children.
AB  - : Placement of a central venous catheter (CVC) in the brachiocephalic vein (BCV)
      via the ultrasound (US)-guided supraclavicular approach was recently described in
      children. We aimed to determine the CVC maintenance-related complications at this
      site compared to the others (i.e., the femoral, the subclavian, and the jugular).
      We performed a retrospective data collection of prospectively registered data on
      CVC in young children hospitalized in a pediatric intensive care unit (PICU)
      during a 4-year period (May 2011 to May 2015). The primary outcome was a
      composite of central line-associated bloodstream infection (CLABSI) and deep-vein
      thrombosis (CLAT) according to the CVC site. Two hundred and twenty-five
      children, with respective age and weight of 7.1 (1.3-40.1) months and 7.7 (3.6
      16) kg, required 257 CVCs, including 147 (57.2%) inserted in the BCV. The risk of
      the primary outcome was lower in the BCV than in the other sites (5.4 vs 16.4%;
      OR: 0.29; 95% CI: 0.12-0.70; p = 0.006). CLABSI incidence density rate (2.8 vs
      8.96 per 1000 catheter days, p < 0.001) and CLAT incidence rate (2.7 vs 10%, p =
      0.016) were also lower at this site. CONCLUSION: BCV catheterization via the US
      guided supraclavicular approach may decrease CVC maintenance-related
      complications in children hospitalized in a PICU. What is Known: * Placement of a
      central venous catheter (CVC) in children is associated with mechanical risks
      during insertion, and with infectious and thrombotic complications during its
      maintenance. * Ultrasound (US)-guided supraclavicular catheterization of the
      brachiocephalic vein (BCV) is feasible in infants and children. What is New: *
      This observational study suggested that BCV catheterization via the US-guided
      supraclavicular approach was associated with a lower risk of CVC insertion and
      maintenance-related complications, compared with the other catheterization sites.

PMID- 29322357
TI  - Community Peer-Led Falls Prevention Presentations: What Do the Experts Suggest?
AB  - Falls among older adults are a major problem. Despite considerable progress in
      falls prevention research, older adults often show low motivation to engage in
      recommended preventive strategies. Peer-led falls prevention education for older
      adults may have potential for bridging the research evidence-practice gap,
      thereby promoting the uptake of falls prevention strategies. We evaluated peer
      educators' presentations of falls prevention education to community-dwelling
      older adults in regard to established criteria that were consistent with adult
      learning principles, the framework of health behaviour change, falls prevention
      guidelines, and recommendations for providing falls prevention information. We
      conducted a within-stage mixed model study using purposive and snowball sampling
      techniques to recruit 10 experts to evaluate video recordings of the delivery of
      three peer-led falls prevention presentations. Each expert viewed three videos
      and rated them using a questionnaire containing both open-ended and closed items.
      There was a good level of expert agreement across the questionnaire domains.
      Though the experts rated some aspects of the presentations highly, they thought
      that the presentations were mainly didactic in delivery, not consistently
      personally relevant to the older adult audience, and did not encourage older
      adults to engage in the preventive strategies that were presented. Based on the
      experts' findings, we developed five key themes and recommendations for the
      effective delivery of peer-led falls prevention presentations. These included
      recommending that peer educators share falls prevention messages in a more
      interactive and experiential manner and that uptake of strategies should be
      facilitated by encouraging the older adults to develop a personalised action
      plan. Findings suggest that if peer-led falls prevention presentations capitalise
      on older adults' capability, opportunity, and motivation, the older adults may be
      more receptive to take up falls prevention messages.

PMID- 29322358
TI  - Anti-hypotensive drug induced cardiotoxicity: an in vitro study.
AB  - Cardiotoxic side effects of broad range of drugs have emerged as an important
      cause of developing cardiovascular complications, as patients recover from one
      disease but develop another. Both cardiovascular and non-cardiovascular drugs may
      lead to the toxicity in the heart. Many drugs were initially not screened for
      cardiotoxicity, which is now an essential concern for drug discovery. Levophed is
      used for treating hypotension in critical care patients. Being a
      neurotransmitter, its concentration increases significantly in stress conditions
      and administration of this drug to patients' results in developing acute as well
      as persistent cardiac complications. Therefore, understanding its concentration
      mediated effects and identifying the toxic concentration will serve as a platform
      to develop interventions to prevent adverse drug effects. In the present study,
      concentration and time-dependent effects of Levophed in H9C2 cardiomyoblasts were
      studied in detail by various cytotoxicity assays. Norepinephrine as a Levophed
      substitute was used and apoptotic cellular death was characterized by Annexin V
      and TUNEL DNA fragmentation assays. Morphological alterations, growth inhibition,
      and cellular death were also studied in detail. We observed that Levophed induces
      concentration-mediated deleterious effects in cardiomyoblasts. In-depth analysis
      of these effects will help in designing strategies in near future to combat and
      reduce this drug-induced cardiac toxicity.

PMID- 29322360
TI  - Highly Conserved Arg Residue of ERFNIN Motif of Pro-Domain is Important for pH
      Induced Zymogen Activation Process in Cysteine Cathepsins K and L.
AB  - Pro-domain of a cysteine cathepsin contains a highly conserved Ex2Rx2Fx2Nx3Ix3N
      (ERFNIN) motif. The zymogen structure of cathepsins revealed that the Arg(R)
      residue of the motif is a central residue of a salt-bridge/H-bond network,
      stabilizing the scaffold of the pro-domain. Importance of the arginine is also
      demonstrated in studies where a single mutation (Arg -> Trp) in human lysosomal
      cathepsin K (hCTSK) is linked to a bone-related genetic disorder
      "Pycnodysostosis". In the present study, we have characterized in vitro Arg ->
      Trp mutant of hCTSK and the same mutant of hCTSL. The R -> W mutant of hCTSK
      revealed that this mutation leads to an unstable zymogen that is spontaneously
      activated and auto-proteolytically degraded rapidly. In contrast, the same mutant
      of hCTSL is sufficiently stable and has proteolytic activity almost like its wild
      type counterpart; however it shows an altered zymogen activation condition in
      terms of pH, temperature and time. Far and near UV circular dichroism and
      intrinsic tryptophan fluorescence experiments have revealed that the mutation has
      minimal effect on structure of the protease hCTSL. Molecular modeling studies
      shows that the mutated Trp31 in hCTSL forms an aromatic cluster with Tyr23 and
      Trp30 leading to a local stabilization of pro-domain and supplements the loss of
      salt-bridge interaction mediated by Arg31 in wild-type. In hCTSK-R31W mutant, due
      to presence of a non-aromatic Ser30 residue such interaction is not possible and
      may be responsible for local instability. These differences may cause detrimental
      effects of R31W mutation on the regulation of hCTSK auto-activation process
      compared to altered activation process in hCTSL.

PMID- 29322361
TI  - Homelessness, Mental Health and Suicidality Among LGBTQ Youth Accessing Crisis
      Services.
AB  - LGBTQ youth experience increased risks of homelessness, mental health disorder
      symptoms, and suicidality. Utilizing data from LGBTQ youth contacting a suicide
      crisis services organization, this study examined: (a) rates of homelessness
      among crisis services users, (b) the relationship between disclosure of LGBTQ
      identity to parents and parental rejection and homelessness, and (c) the
      relationship between homelessness and mental health disorder outcomes and
      suicidality. A nationwide sample of LGBTQ youth was recruited for a confidential
      online survey from an LGBTQ-focused crisis services hotline. Overall, nearly one
      third of youth contacting the crisis services hotline had experienced lifetime
      homelessness, and those who had disclosed their LGBTQ identity to parents or
      experienced parental rejection because of LGBTQ status experienced higher rates
      of homelessness. Youth with homelessness experiences reported more symptoms of
      several mental health disorders and higher rates of suicidality. Suggestions for
      service providers are discussed.

PMID- 29322362
TI  - Implementing a Violence Risk Screening Protocol in a Civil Psychiatric Setting:
      Preliminary Results and Clinical Policy Implications.
AB  - Comprehensive violence risk assessment can require substantial time and
      resources, which may be challenging for an already strapped public mental health
      system. Herein, we describe a naturalistic study of the Fordham Risk Screening
      Tool ("FRST"), a violence risk screening instrument designed to quickly identify
      individuals for whom thorough violence risk assessment would be advisable. All
      patients admitted to one of three state hospitals during the study period
      received FRST screening and HCR-20V3 risk assessment. The FRST reliably and
      accurately identified individuals deemed high risk by the HCR-20V3. The
      implications of these findings, and the broader clinical policy choices are
      reviewed.

PMID- 29322359
TI  - Expression profiles of microRNAs in oxidized low-density lipoprotein-stimulated
      RAW 264.7 cells.
AB  - Macrophage-derived foam cells were one of the hallmarks of atherosclerosis, and
      microRNAs played an important role in the formation of foam cells. In order to
      explore the roles of miRNA in the formation of foam cells, we investigated miRNA
      expression profiles in foam cells through high-throughput sequencing technology.
      A total of 84 miRNAs were differentially expressed between RAW 264.7 macrophages
      and foam cells induced by ox-LDL. Thirty miRNAs were upregulated and 54 miRNAs
      were downregulated. GO terms and KEGG pathways analysis revealed that the target
      genes of most of DE miRNAs were mainly enriched in "cell differentiation,"
      "endocytosis," "MAPK signaling pathway," and "FoxO signaling pathway." The target
      genes of some DE miRNAs were enriched in "Insulin signaling pathway," "Hippo
      signaling pathway," "TNF signaling pathway," "NF-kappa B signaling pathway," and
      "cell death." Using bioinformatics analyses and dual-luciferase reporter assays,
      we found that miR-28a-5p and miR-30c-1-3p directly inhibited LRAD3 and LOX-1 mRNA
      expression through targeting the 3'UTR of LRAD3 and LOX-1 mRNA, respectively. Our
      study indicates that miRNAs are extensively involved in the formation of foam
      cells, and provides a valuable resource for further study the role of miRNAs in
      atherosclerosis.

PMID- 29322363
TI  - A Collective Study on Modeling and Simulation of Resistive Random Access Memory.
AB  - In this work, we provide a comprehensive discussion on the various models
      proposed for the design and description of resistive random access memory (RRAM),
      being a nascent technology is heavily reliant on accurate models to develop
      efficient working designs and standardize its implementation across devices. This
      review provides detailed information regarding the various physical methodologies
      considered for developing models for RRAM devices. It covers all the important
      models reported till now and elucidates their features and limitations. Various
      additional effects and anomalies arising from memristive system have been
      addressed, and the solutions provided by the models to these problems have been
      shown as well. All the fundamental concepts of RRAM model development such as
      device operation, switching dynamics, and current-voltage relationships are
      covered in detail in this work. Popular models proposed by Chua, HP Labs,
      Yakopcic, TEAM, Stanford/ASU, Ielmini, Berco-Tseng, and many others have been
      compared and analyzed extensively on various parameters. The working and
      implementations of the window functions like Joglekar, Biolek, Prodromakis, etc.
      has been presented and compared as well. New well-defined modeling concepts have
      been discussed which increase the applicability and accuracy of the models. The
      use of these concepts brings forth several improvements in the existing models,
      which have been enumerated in this work. Following the template presented, highly
      accurate models would be developed which will vastly help future model developers
      and the modeling community.

PMID- 29322366
TI  - Under pressure: an audit of airway device pressures.

PMID- 29322364
TI  - Changes in Neutrophil Metabolism upon Activation and Aging.
AB  - Neutrophil activation is an important mechanism of host defense against
      pathogens. Chronic inflammation and autoimmunity are often associated with
      abnormalities in phenotype and functions of neutrophils. Since effector functions
      of immune cells during inflammation are tightly linked to their metabolic state,
      changes in neutrophil metabolome upon activation have been investigated in this
      study. Human neutrophils from healthy blood donors (n = 6) were treated either
      with tumor necrosis factor alpha (TNF-alpha) or lipopolysaccharide (LPS), whereas
      untreated neutrophils were used as control. Since apoptotic cells are abundant at
      sites of inflammation, the metabolome of aged, mainly apoptotic neutrophils was
      analyzed too. NMR spectroscopy of water-soluble metabolites revealed a clear
      distinction between aged neutrophils and neutrophils in control and activated
      samples. Higher levels of NAD+ (4- to 9-fold) and lower levels of ATP (0.3-fold),
      glutathione (0.8-fold), hypotaurine (0.8-fold), and phosphocholine (0.6-fold)
      were detected in aged neutrophils than in the other samples. Differences in
      metabolic profiles between LPS and TNF-alpha-stimulated cells as well as between
      stimulated and control neutrophils were statistically not significant.
      Replication with additional six blood donors confirmed increased NAD+ levels in
      aged cells compared to activated and control neutrophils.

PMID- 29322365
TI  - Iron Pots for the Prevention and Treatment of Anemia in Preschoolers.
AB  - OBJECTIVE: To assess the effect of food cooked in iron pots for the prevention
      and treatment of iron deficiency anemia. METHODS: In this cluster randomized
      clinical trial, authors evaluated preschoolers aged 4-5 y for 16 wk. Children
      were cluster randomized to either eating from iron pots (Group A) or aluminum
      pots (Group B). Primary outcome variables were change in hemoglobin concentration
      and anemia prevalence. Two biochemical evaluations were performed, to determine
      Hb concentrations, before and after intervention. This study was conducted in two
      public preschools, located in the municipality of Mucambo, Ceara, in the
      northeast of Brazil. RESULTS: At baseline, for group A, mean hemoglobin
      concentration was 12.26 +/- 1.02 g/dL and 12.29 +/- 0.95 g/dL after intervention,
      p = 0.78. In group B, mean baseline hemoglobin was 12.34 +/- 1.04 g/dL, and 12.13
      +/- 0.86 g/dL after intervention, p = 0.07. All ten participants, who were anemic
      at baseline, were no longer anemic after intervention. CONCLUSIONS: Using iron
      cooking pots in developing countries could provide an innovative strategy to
      prevent and treat iron deficiency anemia.

PMID- 29322367
TI  - In reply: Radial artery spasm treatment by radial, median, or musculocutaneous
      nerve block? A potential therapeutic dilemma.

PMID- 29322368
TI  - Postoperative pain and study design: the type of surgical procedure matters.

PMID- 29322370
TI  - Looking back: The Indian Journal of Gastroenterology 2012-2017.

PMID- 29322371
TI  - Relationship of Parental Genetic Distance with Heterosis and Specific Combining
      Ability in Sesame (Sesamum indicum L.) Based on Phenotypic and Molecular Marker
      Analysis.
AB  - The genetic distance analysis for selection of suitable parents has been
      established and effectively used in many crops; however, there is dearth of
      conclusive report of relationship of genetic distance analysis with heterosis in
      sesame. In the present study, an attempt was made to estimate the associations of
      genetic distances using SSR (GDSSR), seed-storage protein profiling (GDSDS) and
      agro-morphological traits (GDMOR) with hybrid performance. Seven parents were
      selected from 60 exotic and Indian genotypes based on genetic distance from
      clustering pattern based on SSR, seed-storage protein, morphological traits and
      per se performance. For combining ability analysis, 7 parents and 21 crosses
      generated from 7 * 7 half diallel evaluated at two environments in a replicated
      field trial during pre-kharif season of 2013. Compared with the average parents
      yield (12.57 g plant-1), eight hybrids had a significant (P < 0.01) yield
      advantage across environments, with averages of 26.94 and 29.99% for better
      parent heterosis (BPH) and mid-parent heterosis (MPH), respectively, across
      environments. Highly significant positive correlation was observed between
      specific combining ability (SCA) and per se performance (0.97), while positive
      non-significant correlation of BPH with GDSSR (0.048), and non-significant
      negative correlations with GDMOR (- 0.01) and GDSDS (- 0.256) were observed. The
      linear regressions of SCA on MPH, BPH and per se performance of F1s were
      significant with R2 value of 0.88, 0.84 and 0.95 respectively. The present
      findings revealed a weak association of GDSSR with F1's performance; however, SCA
      has appeared as an important factor in the determination of heterosis and per se
      performance of the hybrids. The present findings also indicated that parental
      divergence in the intermediate group would likely produce high heterotic crosses
      in sesame.

PMID- 29322369
TI  - Proteomic and metabolomic analysis of marine medaka (Oryzias melastigma) after
      acute ammonia exposure.
AB  - Ammonia is both a highly toxic environmental pollutant and the major nitrogenous
      waste produced by ammoniotelic teleosts. Although the acute toxic effects of
      ammonia have been widely studied in fish, the biochemical mechanisms of its
      toxicity have not been understood comprehensively. In this study, we performed
      comparative proteomic and metabolomic analysis between ammonia-challenged (1.2
      and 2.6 mmol L-1 NH4Cl for 96 h) and control groups of marine medaka (Oryzias
      melastigma) to identify changes of the metabolite and protein profiles in
      response to ammonia stress. The metabolic responses included changes of multiple
      amino acids, carbohydrates (glucose and glycogen), energy metabolism products
      (ATP and creatinine), and other metabolites (choline and phosphocholine) after
      ammonia exposure, indicating that ammonia mainly caused disturbance in energy
      metabolism and amino acids metabolism. The two-dimensional electrophoresis-based
      proteomic study identified 23 altered proteins, which were involved in nervous
      system, locomotor system, cytoskeleton assembly, immune stress, oxidative stress,
      and signal transduction of apoptosis. These results suggested that ammonia not
      only induced oxidative stress, immune stress, cell injury and apoptosis but also
      affected the motor ability and central nervous system in marine medaka. It is the
      first time that metabolomic and proteomic approaches were integrated to elucidate
      ammonia toxicity in marine fishes. This study is of great value in better
      understanding the mechanisms of ammonia toxicity in marine fishes and in
      practical aspects of aquaculture.

PMID- 29322372
TI  - Examination of Patient-Reported Outcomes in Association with TNF-Inhibitor
      Treatment Response: Results from a US Observational Cohort Study.
AB  - INTRODUCTION: Implementation of a treat-to-target strategy is challenging when
      the patient and physician prioritize different goals. This study aimed to
      "translate" improvements in Clinical Disease Activity Index (CDAI) to concepts
      that resonate with patients (such as pain, fatigue, morning stiffness) by
      examining the association between changes in disease activity and patient
      reported outcomes (PROs) in a national cohort of patients with rheumatoid
      arthritis (RA) initiating their first biologic treatment. METHODS: Patients in
      the Corrona registry with moderate or high disease activity (M/HDA) (defined by a
      CDAI score > 10), prior use of at least one conventional synthetic disease
      modifying antirheumatic drug (csDMARD), 12-month follow-up, and initiating their
      first tumor necrosis factor inhibitor (TNFi) between 1 January 2006 through 1
      November 2015 were identified. Patients were stratified on the basis of CDAI
      during follow-up, and changes in PROs were compared with a test of trend using
      CDAI-defined groups. RESULTS: Of 1570 patients, 37% achieved sustained remission
      or low disease activity (remission/LDA), 15% had improving remission/LDA, 12% had
      worsening M/HDA, and 35% were in sustained M/HDA during 12-month follow-up. Those
      in sustained remission/LDA had greater magnitude of improvement in physical
      functioning, pain, fatigue, morning stiffness, patient's global assessment, and
      quality of life compared with patients in sustained M/HDA (p < 0.001).
      CONCLUSION: Reduction in disease activity was associated with improvements in
      PROs, with the greatest improvements seen in those who achieved sustained
      remission/LDA. These results reinforce the benefits of a treat-to-target approach
      to RA care and may improve dialogue between patients and providers, support
      shared decision-making, and reduce "clinical inertia." FUNDING: Corrona, LLC.

PMID- 29322373
TI  - Epac is required for exogenous and endogenous stimulation of adenosine A2B
      receptor for inhibition of angiotensin II-induced collagen synthesis and
      myofibroblast differentiation.
AB  - Angiotensin II (Ang II) plays an important role on the pathogenesis of cardiac
      fibrosis. Prolong and overstimulation of angiotensin II type 1 receptor with Ang
      II-induced collagen synthesis and myofibroblast differentiation in cardiac
      fibroblasts, leading to cardiac fibrosis. Although adenosine and its analogues
      are known to have cardioprotective effects, the mechanistic by which adenosine A2
      receptors (A2Rs) inhibit Ang II-induced cardiac fibrosis is not clearly
      understood. In the present study, we examined the effects of exogenous adenosine
      and endogenous adenosine on Ang II-induced collagen and myofibroblast
      differentiation determined by alpha-smooth muscle action (alpha-SMA)
      overexpression and their underlying signal transduction. Elevation of endogenous
      adenosine levels resulted in the inhibition of Ang II-induced collagen type I and
      III and alpha-SMA synthesis in cardiac fibroblasts. Moreover, treatment with
      exogenous adenosine which selectively stimulated A2Rs also suppressed Ang II
      induced collagen synthesis and alpha-SMA production. These antifibrotic effects
      of both endogenous and exogenous adenosines are mediated through the A2B receptor
      (A2BR) subtype. Stimulation of A2BR exhibited antifibrotic effects via the cAMP
      dependent and Epac-dependent pathways. Our results provide new mechanistic
      insights regarding the role for cAMP and Epac on A2BR-mediated antifibrotic
      effects. Thus, A2BR is one of the potential therapeutic targets against cardiac
      fibrosis.

PMID- 29322374
TI  - Echocardiographic assessment of regional right ventricular systolic function
      using two-dimensional strain echocardiography and evaluation of the predictive
      ability of longitudinal 2D-strain imaging for pulmonary arterial hypertension in
      systemic sclerosis patients.
AB  - Systemic sclerosis (SSc) is a generalized connective tissue disorder, and SSc
      patients are at risk of developing pulmonary arterial hypertension (PAH). The
      aims of this study are to evaluate the right ventricular regional systolic
      function using two-dimensional speckle-tracking echocardiography (2D STE) and to
      determine the predictive ability of peak longitudinal systolic strain (PLSS) at
      the RV lateral wall for PAH in SSc patients. 80 SSc patients (mean age 51 +/- 12
      years) were included in the study. Echocardiography and 2D STE were performed at
      baseline and after 12 months. RHC was performed only in SSc patients with
      clinical indications. PLSS at the apical segment of the RV free wall was
      significantly impaired in PAH patients compared with non-PH patients (-14.6 +/-
      5.9 vs. - 22.2 +/- 7.5%, p = 0.034). PLSS at the basal, mid, and apical segments
      of the RV free wall was lower in both groups at follow-up compared to baseline,
      but the drop in strain values was statistically significant only in the non-PH
      group (p < 0.05). Right atrial area (OR 1.758; p = 0.023), peak tricuspid
      regurgitation velocity (OR 24.23; p = 0.011) and PLSS at the apical segment of
      the RV lateral wall (OR 2.47; p = 0.005) were independent predictors of PAH. A
      cut-off value of - 14.48% PLSS at the apical segment of the RV lateral wall
      resulted in 100% specificity for predicting PAH in SSc patients. RV pressure
      overload affects RV systolic function as manifested by impaired RV longitudinal
      deformation. Evaluating RV regional systolic function with 2D STE could be useful
      as an additional echocardiographic parameter for screening PAH in SSc patients.

PMID- 29322375
TI  - Predictors of short-term LAMA ineffectiveness in treatment naive patients with
      moderate to severe COPD.
AB  - BACKGROUND: No specific (only subgroup) recommendations for the use of long
      acting muscarinic antagonists in chronic obstructive pulmonary disease (COPD)
      exist. The aim of this exploratory hypothesis generating study was to assess
      whether different phenotypic/endotypic characteristics could be determinants of
      the short-term ineffectiveness of the initial tiotropium bromide monotherapy in
      treatment naive moderate to severe COPD patients. METHODS: A total of 51
      consecutively recruited COPD patients were followed for 3 months after the
      initial evaluation and prescribed initial treatment (tiotropium). Short-term
      treatment ineffectiveness was assessed as a composite measure comprising COPD
      exacerbations, need for additional treatment, and no improvement in functional
      parameters, e.g. 6-min walking test (6MWT), body-mass index, airflow obstruction,
      dyspnea, and exercise (BODE) index and forced expiratory volume in 1 s (FEV1),
      and as single components. RESULTS: Treatment ineffectiveness was significantly
      associated with baseline hemoglobin level, COPD assessment test (CAT) score,
      modified Medical Research Council (mMRC) scale and BODE index (p = 0.002).
      Incident exacerbation during the follow-up was associated with baseline
      bronchoalveolar lavage fluid (BALF) alpha-amylase level and CAT score (p <
      0.001), and change in treatment with leukocyte count, 6MWT desaturation and
      fatigue (p < 0.001). No improvement in 6MWT was associated with baseline CAT
      score, body mass index, mMRC, fatigue, 6MWT and BODE index (p = 0.002). No
      improvement in BODE index was associated with leukocyte count, serum interleukin
      8 (IL-8) and BALF albumin levels (p < 0.001); and no improvement in FEV1 with CAT
      score, baseline vital capacity and BALF tumor necrosis factor alpha (TNF-alpha)
      level (p < 0.001). CONCLUSION: Our results suggest that there is a possibility to
      identify predictors of short-term tiotropium ineffectiveness in patients with
      moderate to severe COPD.

PMID- 29322379
TI  - Attenuation correction and metal artifact reduction in FDG PET/CT for prosthetic
      heart valve and cardiac implantable device endocarditis.

PMID- 29322377
TI  - S(+)-ketamine : Current trends in emergency and intensive care medicine.
AB  - S(+)-ketamine, the pure dextrorotatory enantiomer of ketamine has been available
      for clinical use in analgesia and anesthesia for more than 25 years. The main
      effects are mediated by non-competitive inhibition of the N-methyl-D-aspartate
      (NMDA) receptor but S(+)-ketamine also interacts with opioid receptors, monoamine
      receptors, adenosine receptors and other purinergic receptors. Effects on alpha
      amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, metabotropic
      glutamate receptors (mGluR) and L-type calcium chanels have also been described.
      S(+)-ketamine stimulates the sympathetic nerve system, making it an ideal drug
      for analgosedation or induction of anesthesia in instable patients. In addition,
      the neuroprotective properties, bronchodilatory, antihyperalgesic or
      antiepileptic effects provide interesting therapeutic options. In this article we
      discuss the numerous effects of S(+)-ketamine under pharmacological and clinical
      aspects especially for typical indications in emergency medicine as well as
      intensive care.

PMID- 29322378
TI  - Health literacy, pain intensity and pain perception in patients with chronic
      pain.
AB  - BACKGROUND: Chronic pain poses a large burden for the healthcare system and the
      individuals concerned. The impact of health literacy (HL) on health status and
      health outcomes is receiving more and more attention. The aim of this study was
      to evaluate the association of HL with chronic pain intensity and pain
      perception. METHODS: A total of 121 outpatients suffering from chronic pain (pain
      duration >3 months) were evaluated. The HL was measured using the health literacy
      screening questions. Pain intensity was measured with a Visual Analogue Scale
      (VAS) and pain perception with the short-form McGill Pain Questionnaire (SF-MPQ).
      RESULTS: Individuals with low HL had significantly higher VAS values (Pearson
      correlation coefficient= -0.270, p = 0.003). Stepwise regression analysis showed
      that HL has a significant association with pain intensity (odds ratio [OR] =
      2.31; 95% confidence interval [CI] 1.11-4.83), even after controlling for age and
      sex (OR = 2.27; 95% CI 1.07-4.82), but no longer after controlling for education
      (OR = 2.10; 95% CI 0.95-4.64). CONCLUSION: Individuals with a higher HL showed
      less pain intensity, which seems to be caused by a better pain management;
      therefore, supporting the development of HL in patients with chronic pain could
      be seen as an important objective of integrated care.

PMID- 29322380
TI  - RV function improvement following nitric oxide inhalation demonstrated by gated
      blood pool SPECT in a patient with primary pulmonary hypertension.

PMID- 29322381
TI  - The Genus Coccidella Hambleton (Hemiptera: Rhizoecidae) with Description of Two
      New Species.
AB  - A study was conducted on the Neotropical scale insect genus Coccidella Hambleton
      (Hemiptera: Coccomorpha: Rhizoecidae) based on soil sample material deposited at
      the Hungarian Natural History Museum. Descriptions of the adult females of two
      new Coccidella species, i.e., Coccidella hexapora Kaydan & Konczne Benedicty, sp.
      n. and Coccidella kozari Kaydan & Szita, sp. n., are provided, plus a
      redescription and illustration of adult female of Coccidella kissbalazsi Konczne
      Benedicty & Kozar. An identification key and new additional locality records for
      the currently known Coccidella species are provided and the affinities of the new
      species are discussed.

PMID- 29322382
TI  - Tandem Recruitment and Foraging in the Ponerine Ant Pachycondyla harpax
      (Fabricius).
AB  - Tandem running is a common recruitment strategy in ant species with small colony
      sizes. During a tandem run, an informed leader guides a usually naive nestmate to
      a food source or a nest site. Some species perform tandem runs only during house
      hunting, suggesting that tandem running does not always improve foraging success
      in species known to use tandem running as a recruitment strategy, but more
      natural history information on tandem running under natural conditions is needed
      to better understand the adaptive significance of tandem recruitment in foraging.
      Studying wild colonies in Brazil, we for the first time describe tandem running
      in the ponerine ant Pachycondyla harpax (Fabricius). We asked if foragers perform
      tandem runs to carbohydrate- (honey) and protein-rich (cheese) food items.
      Furthermore, we tested whether the speed and success rate of tandem runs depend
      on the foraging distance. Foragers performed tandem runs to both carbohydrate
      food sources and protein-rich food items that exceed a certain size. The
      probability to perform a tandem run and the travelling speed increase with
      increasing foraging distances, which could help colonies monopolize more distant
      food sources in a competitive environment. Guiding a recruit to a food source is
      costly for leaders as ants are ~66% faster when travelling alone. If tandem runs
      break up (~23% of all tandem runs), followers do not usually discover the food
      source on their own but return to the nest. Our results show that tandem running
      to food sources is common in P. harpax, but that foragers modify their behaviour
      according to the type of food and its distance from the nest. Competition with
      other ants was intense and we discuss how tandem running in P. harpax might help
      colonies to build-up a critical number of ants at large food items that can then
      defend the food source against competitors.

PMID- 29322383
TI  - BMI 35 kg/m2 does not fit everyone: a modified STOP-Bang questionnaire for sleep
      apnea screening in the Chinese population.
AB  - PURPOSE: The STOP-Bang questionnaire is the most widely used to detect surgical
      patients at high risk of obstructive sleep apnea (OSA). However, the body mass
      index (BMI) cutoff value in the original STOP-Bang questionnaire is 35 kg/m2; the
      BMI in the Chinese population is lower than that. We aimed to establish a more
      appropriate BMI cutoff value in the STOP-Bang questionnaire for Chinese patients.
      METHODS: A total of 790 consecutive patients scheduled to undergo surgery at our
      hospital were included in this prospective study. All patients were asked to
      complete the STOP-Bang questionnaire and undergo a 7-h overnight polysomnography
      (PSG). The ability of STOP-Bang questionnaire to detect moderate to severe OSA
      (AHI >= 15 events/h) was assessed. RESULTS: When the BMI cutoff value was set at
      28 kg/m2, the questionnaire had the highest Youden index, although no significant
      differences were found in the sensitivity of the test compared with the original
      BMI cutoff in total and in male patients. In females, changing the BMI cutoff
      value from 35 to 28 kg/m2 resulted in the sensitivity of the test significantly
      increasing from 79.2% (74.9-83.5) to 89.3% (84.4-94.1), while the decrease in
      specificity was minor (from 43.6% [41.2-46.0] to 38.2% [36.1-40.3]), and the
      Youden index was highest (0.27) at this cutoff value. When the STOP-Bang
      questionnaire score was 4, the highest Youden index was obtained. CONCLUSIONS: We
      recommend using a BMI cutoff value (28 kg/m2), and a STOP-Bang score >= 4 allows
      the anesthetist to identify patients with high risk of OSA.

PMID- 29322384
TI  - The Relationship Between Social Affect and Restricted and Repetitive Behaviors
      Measured on the ADOS-2 and Maternal Stress.
AB  - This study investigated categories of autism spectrum disorder (ASD) symptoms
      measured by the Autism Diagnostic Observation Schedule-Second Edition and their
      association with maternal stress. Social affect and restricted and repetitive
      behaviors were compared with levels of maternal stress, measured by the Parenting
      Stress Index, in 102 children with ASD ages 2-12 years of age. Results indicated
      that social affect and restricted and repetitive behaviors were associated with
      the mother's stress regarding acceptability of the child's condition.
      Additionally, restricted and repetitive behaviors were significantly related to
      stress involving the child's hyperactivity and impulsivity. These findings
      highlight specific areas of stress experienced by mothers of children with ASD
      that are related to the child's symptoms, providing information for caregiver
      support and intervention.

PMID- 29322385
TI  - Associations Between Resilience and the Well-Being of Mothers of Children with
      Autism Spectrum Disorder and Other Developmental Disabilities.
AB  - There is variability in the extent to which mothers are affected by the behavior
      problems of their children with developmental disabilities (DD). We explore
      whether maternal resilience functions as a protective or compensatory factor. In
      Studies 1 and 2, using moderated multiple regression models, we found evidence
      that maternal resilience functioned as a compensatory factor-having a significant
      independent main effect relationship with well-being outcomes in mothers of
      children with DD and autism spectrum disorder. However, there was no longitudinal
      association between resilience and maternal well-being outcomes. There was little
      evidence of the role of resilience as a protective factor between child behavior
      problems and maternal well-being in both studies.

PMID- 29322387
TI  - Giant panda foraging and movement patterns in response to bamboo shoot growth.
AB  - Diet plays a pivotal role in dictating behavioral patterns of herbivorous
      animals, particularly specialist species. The giant panda (Ailuropoda
      melanoleuca) is well-known as a bamboo specialist. In the present study, the
      response of giant pandas to spatiotemporal variation of bamboo shoots was
      explored using field surveys and GPS collar tracking. Results show the dynamics
      in panda-bamboo space-time relationships that have not been previously
      articulated. For instance, we found a higher bamboo stump height of foraged
      bamboo with increasing elevation, places where pandas foraged later in spring
      when bamboo shoots become more fibrous and woody. The time required for shoots to
      reach optimum height for foraging was significantly delayed as elevation
      increased, a pattern which corresponded with panda elevational migration patterns
      beginning from the lower elevational end of Fargesia robusta distribution and
      gradually shifting upward until the end of the shooting season. These results
      indicate that giant pandas can respond to spatiotemporal variation of bamboo
      resources, such as available shoots. Anthropogenic interference of low-elevation
      F. robusta habitat should be mitigated, and conservation attention and increased
      monitoring should be given to F. robusta areas at the low- and mid-elevation
      ranges, particularly in the spring shooting season.

PMID- 29322386
TI  - Independent risk factors for mortality in critically ill patients with candidemia
      on Italian Internal Medicine Wards.
AB  - Candida is an increasing cause of bloodstream infection and is associated with
      significant morbidity and mortality. The aim of our study is to analyze risk
      factors for short-term mortality in patients with bloodstream Candida spp.
      infections admitted to Internal Medicine Wards (IMWs). This was a retrospective
      case-control study between January 2012 and December 2014 from four University
      Hospitals in Italy, where patients with candidemia dying within 30 days from
      diagnosis were matched to control cases with candidemia who survived in the same
      period of time. Two-hundred and fifty cases of candidemia were registered during
      the 36 months of enrollment. Among these, 112 patients died (45%) within 30 days
      from the first blood culture's positivity for Candida spp. At multivariate
      analysis, septic shock [odds ratio (95% CI) = 2.919 (1.62-5.35), p < 0.001] and
      concomitant chronic kidney failure [odds ratio (95% CI) = 2.296 (1.07-5.12), p =
      0.036] were independent predictors of mortality. Low-dose chronic steroid therapy
      was protective [odds ratio (95% CI) = 0.461 (0.25-0.83), p = 0.011).

PMID- 29322388
TI  - Decision support system for management of reactive nitrogen flows in wastewater
      system.
AB  - The change in nitrogen balance causes many environmental and socioeconomic
      impacts. In relation to food production and nitrogen release in wastewater
      systems, wastewater and sludge discharge and mineral fertilizer use intensify
      nitrogen imbalance of a region. The replacement of mineral fertilizer by nitrogen
      from treated wastewater, biosolids, and treated urine is a promising alternative.
      This work presents a model to support decision taking for the management of
      reactive nitrogen flows in wastewater systems based on system dynamics. Six
      scenarios were simulated for nitrogen flows in wastewater systems and related
      components.

PMID- 29322389
TI  - Performance of ceramic ultrafiltration and reverse osmosis membranes in treating
      car wash wastewater for reuse.
AB  - Reusing treated effluents in industries is a great option to conserve freshwater
      resources. For example, car wash centres all over Australia are estimated to use
      17.5 billion litres of water and discharge it as wastewater and spend $75 million
      a year for both purchasing fresh water and for treating and/or discharging the
      wastewater. Therefore, it is important to develop simple but reliable systems
      that can help to treat and reuse car wash wastewater. Significant savings could
      also be associated with the implementation of such systems. This study evaluates
      the performance of granular and membrane filtration systems with
      coagulation/flocculation and sedimentation in treating car wash wastewater for
      the purpose of reuse. Overall, 99.9% of turbidity, 100% of suspended solids and
      96% of COD were removed from the car wash wastewater after treating by
      coagulation, flocculation, sedimentation, sand filtration, ceramic
      ultrafiltration and reverse osmosis and the treated water meets the standards
      required for class A recycled water in Australia and standards imposed in Belgium
      and China. The treated water can be reused. However, optimisation is required to
      reduce the sludge produced by this system.

PMID- 29322391
TI  - Feet in danger: short exposure to contaminated soil causing health damage-an
      experimental study.
AB  - In this study, hematological and behavioral changes in Wistar rats exposed to
      soil collected from urban areas next to an industrial complex were investigated.
      Animals were exposed to soil samples placed at the bottom of cages for 4 days.
      After this period, behavioral parameters were measured by the open field test and
      the elevated plus-maze. Blood was collected to measure hematological parameters.
      The soil from the vicinity of the oil refining industry caused changes in
      hematological parameters and altered behavioral parameters in both tests. The
      soil from the vicinity of the petroleum refining industry and fertilizer
      industries increased the density of white blood cells and decreased exploratory
      activity in the exposed animals. The results demonstrate that contact with
      contaminated soils, even for short periods, can cause physiological damage in
      organisms and that special attention should be given to people who live under
      constant exposure to these soils.

PMID- 29322392
TI  - Effect of inorganic and organic solutes on zero-valent aluminum-activated
      hydrogen peroxide and persulfate oxidation of bisphenol A.
AB  - The effect of varying inorganic (chloride, nitrate, sulfate, and phosphate) and
      organic (represented by humic acid) solutes on the removal of aqueous
      micropollutant bisphenol A (BPA; 8.8 MUM; 2 mg/L) with the oxidizing agents
      hydrogen peroxide (HP; 0.25 mM) and persulfate (PS; 0.25 mM) activated using zero
      valent aluminum (ZVA) nanoparticles (1 g/L) was investigated at a pH of 3. In the
      absence of the solutes, the PS/ZVA treatment system was superior to the HP/ZVA
      system in terms of BPA removal rates and kinetics. Further, the HP/ZVA process
      was not affected by nitrate (50 mg/L) addition, whereas chloride (250 mg/L)
      exhibited no effect on the PS/ZVA process. The negative effect of inorganic
      anions on BPA removal generally speaking increased with increasing charge in the
      following order: NO3- (no inhibition) < Cl- (250 mg/L) = SO42- < PO43- for HP/ZVA
      and Cl- (250 mg/L; no inhibition) < NO3- < SO42- < PO43- for PS/ZVA. Upon
      addition of 20 mg/L humic acid representing natural organic matter, BPA removals
      decreased from 72 and 100% in the absence of solutes to 24 and 57% for HP/ZVA and
      PS/ZVA treatments, respectively. The solute mixture containing all inorganic and
      organic solutes together partly suppressed the inhibitory effects of phosphate
      and humic acid on BPA removals decreasing to 46 and 43% after HP/ZVA and PS/ZVA
      treatments, respectively. Dissolved organic carbon removals were obtained in the
      range of 30 and 47% (the HP/ZVA process), as well as 47 and 57% (the PS/ZVA
      process) for the experiments in the presence of 20 mg/L humic acid and solute
      mixture, respectively. The relative Vibrio fischeri photoluminescence inhibition
      decreased particularly for the PS/ZVA treatment system, which exhibited a higher
      treatment performance than the HP/ZVA treatment system.

PMID- 29322390
TI  - Authentication of synthetic environmental contaminants and their
      (bio)transformation products in toxicology: polychlorinated biphenyls as an
      example.
AB  - Toxicological studies use "specialty chemicals" and, thus, should assess and
      report both identity and degree of purity (homogeneity) of the chemicals (or
      toxicants) under investigation to ensure that other scientists can replicate
      experimental results. Although detailed reporting criteria for the synthesis and
      characterization of organic compounds have been established by organic chemistry
      journals, such criteria are inconsistently applied to the chemicals used in
      toxicological studies. Biologically active trace impurities may lead to incorrect
      conclusions about the chemical entity responsible for a biological response,
      which in turn may confound risk assessment. Based on our experience with the
      synthesis of PCBs and their metabolites, we herein propose guidelines for the
      "authentication" of synthetic PCBs and, by extension, other organic toxicants,
      and provide a checklist for documenting the authentication of toxicants reported
      in the peer-reviewed literature. The objective is to expand guidelines proposed
      for different types of biomedical and preclinical studies to include a thorough
      authentication of specialty chemicals, such as PCBs and their derivatives, with
      the goal of ensuring transparent and open reporting of scientific results in
      toxicology and the environmental health sciences.

PMID- 29322393
TI  - Contribution of ammonia-oxidizing archaea and ammonia-oxidizing bacteria to
      ammonia oxidation in two nitrifying reactors.
AB  - In this study, two laboratory nitrifying reactors (NRI and NRII), which were
      seeded by sludge from different sources and operated under different operating
      conditions, were found to possess distinct dominant ammonia-oxidizing
      microorganisms. Ammonia-oxidizing archaeal (AOA) amoA genes outnumbered ammonia
      oxidizing bacterial (AOB) amoA genes in reactor NRI, while only AOB amoA genes
      were detectable in reactor NRII. The AOA amoA gene sequences retrieved from NRI
      were characterized within the Nitrososphaera sister cluster of the group 1.1b
      Thaumarchaeota. Two inhibitors for ammonia oxidation, allylthiourea (ATU) and 2
      phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (PTIO), were applied
      individually and as a mixture to observe the ammonia-oxidizing activity of both
      microorganisms in the reactors' sludge. The results indicated that AOA and AOB
      jointly oxidized ammonia in NRI, while AOB played the main role in ammonia
      oxidation in NRII. DNA-stable isotope probing with labeled 13C-HCO3- was
      performed on NRI sludge. Incorporation of 13C into AOA and AOB implied that both
      microorganisms may perform autotrophy during ammonia oxidation. Taken together,
      the results from this study provide direct evidence demonstrating the
      contribution of AOA and AOB to ammonia oxidation in the nitrifying reactors.

PMID- 29322394
TI  - Removal of cadmium in aqueous solution using wheat straw biochar: effect of
      minerals and mechanism.
AB  - The biochars were produced from wheat straw (WSBC) at different pyrolytic
      temperatures. Biochars were characterized by multiple instrumental techniques and
      were applied to remove Cd from aqueous solution. The removal mechanism was
      explored, and the quantitative information regarding the relative contribution of
      related mechanisms to Cd sorption on biochars was provided. The results showed
      that pseudo-second-order kinetic model, TC (two-compartment) model, and
      Freundlich isotherm could well fit the process of Cd sorption on biochars. The
      sorption could be divided into fast and slow adsorption stages. The order of the
      Cd removal capacity by biochar was WSBC700 > WSBC500 > WSBC300. Adsorption amount
      of Cd by biochar reduced when the biochar was rinsed with 1.0 M HCl, which
      indicated that acid-soluble minerals in biochar played an important role during
      the Cd removal process, especially for the biochar obtained at high pyrolytic
      temperature. Various equipments were used to investigate the interaction
      mechanism between biochar and Cd. Mineral precipitation, surface complexation,
      and cation-pi interaction were the main mechanisms of Cd sorption on the
      biochars. The contribution of cation-pi mechanism was in the range of 25.42
      48.58%, 2.18-19.30% for surface complexation and 32.12-72.41% for mineral
      precipitation, respectively. The pyrolytic temperature significantly influenced
      the removal capacity and mechanism of Cd on biochars. The cation-pi mechanism was
      predominant for biochar obtained at lower pyrolytic temperature. However, mineral
      precipitation mechanism played a crucial role for biochar obtained at high
      pyrolytic temperature. These results are helpful for the design or screening of
      "engineered biochar" to act as sorbents to remove or immobilized Cd in polluted
      soil or water. Graphical abstract ?.

PMID- 29322395
TI  - Lead, zinc, and cadmium uptake, accumulation, and phytoremediation by plants
      growing around Tang-e Douzan lead-zinc mine, Iran.
AB  - In the current study, soils of Tang-e Douzan mine, located in Isfahan, Iran, were
      collected and analyzed for soluble, exchangeable, and total amounts of Pb, Zn,
      Cd, Ca, and Mg. The maximum Pb, Zn, Cd, Ca, and Mg concentrations in soils were
      2500, 1100, 59, 43,800, and 1320 mg/kg for total metals, 86, 83, 6.3, 4650, and
      48 mg/kg for their exchangeable fractions, and 59, 3.7, 0.53, 430, and 6.4 mg/kg
      for their soluble fractions, respectively. All specimens collected, including 69
      plant species, were analyzed for Pb, Zn, and Cd. Moreover, their phytoremediation
      potential was investigated by calculating bioconcentration factors (BCF),
      translocation factors (TF), and extraction factors (EF) for each heavy metal.
      Analysis of the leaves for heavy metals showed no metal hyperaccumulation. The
      highest shoot concentrations of Pb (298 mg/kg) and Zn (740 mg/kg) were found in
      Roemeria hybrida subsp. dodecandra and Cd (43 mg/kg) in Chenopodium foliosum.
      Plants having BCFs and TFs > 1 are capable of phytoextraction. Among the analyzed
      species, four had both TFs and BCFs > 1 for Zn, 13 for Cd, and none for Pb. R.
      hybrida, Bromus squarrosus, Descurainia sophia, and Poa bulbosa seem to be the
      best choices for phytoextraction of Zn. Aegilops columnaris, Allium ampeloprasum
      subsp. iranicum, B. squarrosus, and Cousinia piptocephala are the best choices
      for phytoextraction of Cd. Plants with BCF > 1 and TF < 1, including Cerastium
      dichotomum and Muscari neglectum for Pb, Ceratocephala falcata, M. neglectum,
      Ornithogalum orthophyllum, and Ranunculus arvensis for Zn and C. falcata, M.
      neglectum, O. orthophyllum, and R. hybrida subsp. dodecandra for Cd, are proposed
      to be the most efficient species for metal phytostabilization.

PMID- 29322396
TI  - Editorial: Special Issue "Effect-related evaluation of anthropogenic trace
      substances-concepts for genotoxicity, neurotoxicity and endocrine effects".

PMID- 29322397
TI  - Overlapping and distinct neural metabolic patterns related to impulsivity and
      hypomania in Parkinson's disease.
AB  - Impulsivity and hypomania are common non-motor features in Parkinson's disease
      (PD). The aim of this study was to find the overlapping and distinct neural
      correlates of these symptoms in PD. Symptoms of impulsivity and hypomania were
      assessed in 24 PD patients using the Barratt Impulsiveness Scale (BIS-11) and
      Self-Report Manic Inventory (SRMI), respectively. In addition, fluorodeoxyglucose
      positron emission tomography (FDG-PET) imaging for each individual was performed.
      We conducted two separate multiple regression analyses for BIS-11 and SRMI scores
      with FDG-PET data to identify the brain regions that are associated with both
      impulsivity and hypomania scores, as well as those exclusive to each symptom.
      Then, seed-based functional connectivity analyses on healthy subjects identified
      the areas connected to each of the exclusive regions and the overlapping region,
      used as seeds. We observed a positive association between BIS-11 and SRMI scores
      and neural metabolism only in the prefrontal areas. Conjunction analysis revealed
      an overlapping region in the middle frontal gyrus. Regions exclusive to
      impulsivity were found in the medial part of the right superior frontal gyrus and
      regions exclusive to hypomania were in the right superior frontal gyrus, right
      precentral gyrus and right paracentral lobule. Connectivity patterns of seeds
      exclusively related to impulsivity were different from those for hypomania in
      healthy brains. These results provide evidence of both overlapping and distinct
      regions linked with impulsivity and hypomania scores in PD. The exclusive regions
      for each characteristic are connected to specific intrinsic functional networks.

PMID- 29322398
TI  - Hepatitis C virus infection and development of type 2 diabetes mellitus:
      Systematic review and meta-analysis of the literature.
AB  - Type 2 diabetes mellitus (T2DM) is an endocrine disorder encompassing
      multifactorial mechanisms, and chronic hepatitis C virus infection (CHC) is a
      multifaceted disorder, associated with extrahepatic manifestations, including
      endocrinological disorders. CHC and T2DM are associated, but the subject remains
      controversial. We performed a systematic review and meta-analysis evaluating such
      association, searching on PubMed until February 29, 2016. Inclusion criteria
      were: 1) presence of at least one internal control group age- and gender-matched
      (non-hepatopathic controls; and/or hepatopathic, not HCV-positive, controls); 2)
      sufficient data to calculate odds ratio and relative risk. Exclusion criteria
      were: 1) literature reviews on the topic; 2) publications regarding special
      populations [human immunodeficiency virus and human T-lymphotropic virus-1
      coinfections, hepatocellular carcinoma (HCC), post-transplantation DM, gender
      selection]; 3) no clear differentiation among HCV patients with CHC, cirrhosis or
      HCC. Data from each study were independently extracted by two reviewers and cross
      checked by AA. Our systematic review returned 544 records, and 33 were included
      in our meta-analysis. HCV infection is associated with an increased risk of T2DM
      independently from the severity of the associated liver disease, in CHC and
      cirrhotic HCV patients. As expected T2DM risk is higher in cirrhotic HCV
      patients, than CHC, and the prevalence of HCV infection in T2DM patients is
      higher than in non-diabetic controls. Regarding HBV infection prevalence, no
      difference exists in diabetic and non-diabetic subjects. An unequivocal CHC and
      T2DM association was shown. A proactive, integrated approach to HCV and T2DM
      therapies should maximize benefits of both diseases treatment.

PMID- 29322399
TI  - When is best-worst best? A comparison of best-worst scaling, numeric estimation,
      and rating scales for collection of semantic norms.
AB  - Large-scale semantic norms have become both prevalent and influential in recent
      psycholinguistic research. However, little attention has been directed towards
      understanding the methodological best practices of such norm collection efforts.
      We compared the quality of semantic norms obtained through rating scales, numeric
      estimation, and a less commonly used judgment format called best-worst scaling.
      We found that best-worst scaling usually produces norms with higher predictive
      validities than other response formats, and does so requiring less data to be
      collected overall. We also found evidence that the various response formats may
      be producing qualitatively, rather than just quantitatively, different data. This
      raises the issue of potential response format bias, which has not been addressed
      by previous efforts to collect semantic norms, likely because of previous
      reliance on a single type of response format for a single type of semantic
      judgment. We have made available software for creating best-worst stimuli and
      scoring best-worst data. We also made available new norms for age of acquisition,
      valence, arousal, and concreteness collected using best-worst scaling. These
      norms include entries for 1,040 words, of which 1,034 are also contained in the
      ANEW norms (Bradley & Lang, Affective norms for English words (ANEW): Instruction
      manual and affective ratings (pp. 1-45). Technical report C-1, the center for
      research in psychophysiology, University of Florida, 1999).

PMID- 29322400
TI  - General mixture item response models with different item response structures:
      Exposition with an application to Likert scales.
AB  - This article proposes a general mixture item response theory (IRT) framework that
      allows for classes of persons to differ with respect to the type of processes
      underlying the item responses. Through the use of mixture models, nonnested IRT
      models with different structures can be estimated for different classes, and
      class membership can be estimated for each person in the sample. If researchers
      are able to provide competing measurement models, this mixture IRT framework may
      help them deal with some violations of measurement invariance. To illustrate this
      approach, we consider a two-class mixture model, where a person's responses to
      Likert-scale items containing a neutral middle category are either modeled using
      a generalized partial credit model, or through an IRTree model. In the first
      model, the middle category ("neither agree nor disagree") is taken to be
      qualitatively similar to the other categories, and is taken to provide
      information about the person's endorsement. In the second model, the middle
      category is taken to be qualitatively different and to reflect a nonresponse
      choice, which is modeled using an additional latent variable that captures a
      person's willingness to respond. The mixture model is studied using simulation
      studies and is applied to an empirical example.

PMID- 29322401
TI  - Is it possible to cure the symptoms of the overactive bladder in women?
AB  - PURPOSE: To evaluate the feasibility of discontinuing treatment with mirabegron
      once symptoms have subsided in patients with overactive bladder (OAB). METHODS:
      The present study evaluated a total of 159 female OAB patients (age 62.9 +/-
      12.36), each of which were prescribed 50 mg/day mirabegron (Time point 1-T1).
      Data obtained from voiding diaries and patient-reported outcome variables were
      assessed during follow-up visits at months 1, 3, 6, 12, 18 (T2), and 21 (T4). At
      the 18-month visit, patients with an Urgency Bother-Visual Analog Scale score of
      <= 50% were advised to stop treatment with mirabegron. Upon re-emergence or
      worsening of OAB symptoms, patients were allowed to start taking medication again
      at their discretion (T3). Statistical analysis was performed using a Chi-square
      test. An ANOVA analysis and a two-sample t test were used to evaluate differences
      between groups. RESULTS: A total of 56 out of 159 (35.3%) patients took 50 mg of
      mirabegron daily between T1 and T2. A total of 17 out of 56 patients (30.4%) did
      not meet the criteria for mirabegron discontinuation (Group A). A total of 24 out
      of 56 patients (42.9%) stopped taking the medication temporarily, but later
      returned to treatment (Group B). The average time span between T2 and T3 was 53.9
      days. Fifteen of 56 patients (26.8%) ceased treatment with mirabegron without
      starting it again before T4 (Group C). The average time span between T2 and T4,
      in Group C, was 124.7 days. CONCLUSION: A small percentage of OAB patients were
      able to discontinue mirabegron due to symptom cessation.

PMID- 29322402
TI  - Laser treatment of primary axillary hyperhidrosis: a review of the literature.
AB  - Hyperhidrosis o'ccurs when the body produces sweat beyond what is essential to
      maintain thermal homeostasis. The condition tends to occur in areas marked by
      high-eccrine density such as the axillae, palms, and soles and less commonly in
      the craniofacial area. The current standard of care is topical aluminum chloride
      hexahydrate antiperspirant (10-20%), but other treatments such as
      anticholinergics, clonidine, propranolol, antiadrenergics, injections with
      attenuated botulinum toxin, microwave technology, and surgery have been
      therapeutically implicated as well. Yet, many of these treatments have limited
      efficacy, systemic side effects, and may be linked with significant surgical
      morbidity, creating need for the development of new and effective therapies for
      controlling excessive sweating. In this literature review, we examined the use of
      lasers, particularly the Neodynium:Yttrium-Aluminum-Garnet (Nd:YAG) and diode
      lasers, in treating hyperhidrosis. Due to its demonstrated effectiveness and
      limited side effect profile, our review suggests that Nd:YAG laser may be a
      promising treatment modality for hyperhidrosis. Nevertheless, additional large,
      randomized controlled trials are necessary to confirm the safety and efficacy of
      this treatment option.

PMID- 29322403
TI  - Divorce, Separation, and Housing Changes: A Multiprocess Analysis of Longitudinal
      Data from England and Wales.
AB  - This study investigates the effect of marital and nonmarital separation on
      individuals' residential and housing trajectories. Using rich data from the
      British Household Panel Survey (BHPS) and applying multilevel competing-risks
      event history models, we analyze the risk of a move of single, married,
      cohabiting, and separated men and women to different housing types. We
      distinguish moves due to separation from moves of separated people and account
      for unobserved codeterminants of moving and separation risks. Our analysis shows
      that many individuals move due to separation, as expected, but that the
      likelihood of moving is also relatively high among separated individuals. We find
      that separation has a long-term effect on individuals' residential careers.
      Separated women exhibit high moving risks regardless of whether they moved out of
      the joint home upon separation, whereas separated men who did not move out upon
      separation are less likely to move. Interestingly, separated women are most
      likely to move to terraced houses, whereas separated men are equally likely to
      move to flats (apartments) and terraced (row) houses, suggesting that family
      structure shapes moving patterns of separated individuals.

PMID- 29322404
TI  - In Vivo Models of Inflammatory Bowel Disease and Colitis-Associated Cancer.
AB  - A single layer of epithelial cells separates luminal antigens from the host
      immune system throughout the gastrointestinal tract. A breakdown in the integrity
      of the epithelial barrier can lead to chronic inflammation, which is associated
      with numerous complications including cancer. Here we describe three experimental
      protocols to chemically induce acute and chronic inflammatory bowel disease (IBD)
      symptoms and colitis-associated colorectal cancer (CRC) progression. These in
      vivo mouse models are based on the induction of damage to the colonic epithelium,
      resulting in an inflammatory and wound healing response. In addition, we outline
      colonoscopy procedures to monitor the onset of disease in individual live mice.

PMID- 29322405
TI  - Combining Cell Type-Restricted Adenoviral Targeting with Immunostaining and Flow
      Cytometry to Identify Cells-of-Origin of Lung Cancer.
AB  - Lung cancers display considerable intertumoral heterogeneity, leading to the
      classification of distinct tumor subtypes. Our understanding of the genetic
      aberrations that underlie tumor subtypes has been greatly enhanced by recent
      genomic sequencing studies and state-of-the-art gene targeting technologies,
      highlighting evidence that distinct lung cancer subtypes may be derived from
      different "cells-of-origin". Here, we describe the intra-tracheal delivery of
      cell type-restricted Ad5-Cre viruses into the lungs of adult mice, combined with
      immunohistochemical and flow cytometry strategies for the detection of lung
      cancer-initiating cells in vivo.

PMID- 29322406
TI  - Utility of Endoscopic Ultrasound-Guided Fine-Needle Aspiration for Preclinical
      Evaluation of Therapies in Cancer.
AB  - Personalising cancer therapy is a way of improving treatment efficacy, by
      selecting specific treatments for patients with certain molecular changes to
      their tumour. This requires both molecular material to detect these targets and a
      preclinical disease model to demonstrate treatment efficacy. In pancreatic cancer
      this is problematic, as most patients present with advanced disease and are
      therefore ineligible for surgery. As a result, biological material derived from
      such patients has been excluded from all preclinical studies in personalised
      medicine. This chapter presents methodology to achieve both of the above
      mentioned requirements using endoscopic ultrasound-guided fine-needle aspiration,
      which can be offered to nearly all patients with early or advanced disease.

PMID- 29322407
TI  - Modelling Intestinal Carcinogenesis Using In Vitro Organoid Cultures.
AB  - Mouse models of intestinal carcinogenesis are very powerful for studying the
      impact of specific mutations on tumour initiation and progression. Mutations can
      be studied both singularly and in combination using conditional alleles that can
      be induced in a temporal manner. The steps in intestinal carcinogenesis are
      complex and can be challenging to image in live animals at a cellular level. The
      ability to culture intestinal epithelial tissue in three-dimensional organoids in
      vitro provides an accessible system that can be genetically manipulated and
      easily visualised to assess specific biological impacts in living tissue. Here,
      we describe methodology for conditional mutation of genes in organoids from
      genetically modified mice via induction of Cre recombinase induced by tamoxifen
      or by transient exposure to TAT-Cre protein. This methodology provides a rapid
      platform for assessing the cellular changes induced by specific mutations in
      intestinal tissue.

PMID- 29322408
TI  - Protocols to Evaluate Cigarette Smoke-Induced Lung Inflammation and Pathology in
      Mice.
AB  - Cigarette smoking is a major cause of chronic obstructive pulmonary disease
      (COPD). Inhalation of cigarette smoke causes inflammation of the airways, airway
      wall remodelling, mucus hypersecretion and progressive airflow limitation. Much
      of the disease burden and health care utilisation in COPD is associated with the
      management of its comorbidities and infectious (viral and bacterial)
      exacerbations (AECOPD). Comorbidities, in particular skeletal muscle wasting,
      cardiovascular disease and lung cancer markedly impact on disease morbidity,
      progression and mortality. The mechanisms and mediators underlying COPD and its
      comorbidities are poorly understood and current COPD therapy is relatively
      ineffective. Many researchers have used animal modelling systems to explore the
      mechanisms underlying COPD, AECOPD and comorbidities of COPD with the goal of
      identifying novel therapeutic targets. Here we describe a mouse model that we
      have developed to define the cellular, molecular and pathological consequences of
      cigarette smoke exposure and the development of comorbidities of COPD.

PMID- 29322409
TI  - Tracking Competent Host Defence to Chronic Inflammation: An In Vivo Model of
      Peritonitis.
AB  - Anti-microbial host defence is dependent on the rapid recruitment of inflammatory
      cells to the site of infection, the elimination of invading pathogens, and the
      efficient resolution of inflammation so as to minimise damage to the host. The
      peritoneal cavity provides an easily accessible and physiologically relevant
      system where the delicate balance of these processes may be studied. Here, we
      describe murine models of peritoneal inflammation that enable studies of both
      competent anti-microbial immunity and inflammation associated tissue damage as a
      consequence of recurrent bacterial challenge. The inflammatory hallmarks of these
      models reflect the clinical and molecular features of peritonitis episodes seen
      in renal failure patients on peritoneal dialysis. Development of these models
      relies on the preparation of a cell-free supernatant derived from an isolate of
      Staphylococcus epidermidis (termed SES). Intraperitoneal administration of SES
      induces a TLR2-driven acute inflammatory response that is characterised by an
      initial transient influx of neutrophils that are replaced by a more sustained
      recruitment of mononuclear cells and lymphocytes. Adaptation of this model using
      a repeated administration of SES allows investigations into the development of
      adaptive immunity and memory responses, and the hallmarks associated with tissue
      remodelling and fibrosis. These models are therefore clinically relevant and
      provide exciting opportunities to study both innate and adaptive immune responses
      in the control of bacterial infection and pathogenesis.

PMID- 29322410
TI  - Citrobacter rodentium Infection Model for the Analysis of Bacterial Pathogenesis
      and Mucosal Immunology.
AB  - Citrobacter rodentium is a mouse restricted pathogen that was originally isolated
      from laboratory mouse colonies and causes transmissible colonic hyperplasia,
      characterized by thickening of the colon and inflammation. As a natural pathogen
      of mice, the infection model has proven critical to the development of our
      understanding of the pathogenesis of enteric disease and the mucosal immune
      response. In addition to this, some features of disease such as dysbiosis,
      inflammation, and wound healing replicate features of human inflammatory bowel
      diseases. As such, the C. rodentium infection model has become a key tool in
      investigations of many aspects of mucosal immunology.

PMID- 29322411
TI  - In Vivo Infection Model of Severe Influenza A Virus.
AB  - The lung is constantly exposed to both environmental and microbial challenge. As
      a "contained" organ, it also constitutes an excellent "self-contained" tissue to
      examine inflammatory responses and cellular infiltration into a diseased organ.
      Influenza A virus (IAV) causes both mild and severe inflammation that is strain
      specific following infection of the lung epithelium that spreads to other cells
      of the lung environment. Here, we describe a method of intranasal inoculation of
      the lung with IAV that can be used as a preclinical model of infection. Mice can
      be monitored for clinical signs of infection and tissue and lung fluid collected
      for further analysis to dissect the immunological consequences of IAV infection.
      Importantly, this method can be modified to introduce other pathogens, therapies
      and environmental stimuli to examine immune responses in the lung.

PMID- 29322413
TI  - Isolation of Mouse Primary Gastric Epithelial Cells to Investigate the Mechanisms
      of Helicobacter pylori Associated Disease.
AB  - The gastrointestinal epithelium provides the first line of defense against
      invading pathogens, among which Helicobacter pylori is linked to numerous gastric
      pathologies, including chronic gastritis and cancer. Primary gastric epithelial
      cells represent a useful model for the investigation of the underlying molecular
      and cellular mechanisms involved in these H. pylori associated diseases. In this
      chapter, we describe a method for the isolation of primary gastric epithelial
      cells from mice and detection of epithelial cell adhesion molecule (EpCAM)
      expression in the isolated cells.

PMID- 29322412
TI  - In Vivo Models for Inflammatory Arthritis.
AB  - In vivo mouse models of inflammatory arthritis are extensively used to
      investigate pathogenic mechanisms governing inflammation-driven joint damage. Two
      commonly utilized models include collagen-induced arthritis (CIA) and methylated
      bovine serum albumin (mBSA) antigen-induced arthritis (AIA). These offer unique
      advantages for modeling different aspects of human disease. CIA involves breach
      of immunological tolerance resulting in systemic autoantibody-driven arthritis,
      while AIA results in local resolving inflammatory flares and articular T cell
      mediated damage. Despite limitations that apply to all animal models of human
      disease, CIA and AIA have been instrumental in identifying pathogenic mediators,
      immune cell subsets and stromal cell responses that determine disease onset,
      progression, and severity. Moreover, these models have enabled investigation of
      disease phases not easily studied in patients and have served as testing beds for
      novel biological therapies, including cytokine blockers and small molecule
      inhibitors of intracellular signaling that have revolutionized rheumatoid
      arthritis treatment.

PMID- 29322414
TI  - Dissecting Interleukin-6 Classic- and Trans-Signaling in Inflammation and Cancer.
AB  - Interleukin-6 is a cytokine synthesized by many cells in the human body. IL-6
      binds to a membrane bound IL-6R, which is only present on hepatocytes, some
      epithelial cells and some leukocytes. The complex of IL-6 and IL-6R binds to the
      ubiquitously expressed receptor subunit gp130, which forms a homodimer and
      thereby initiates intracellular signaling via the JAK/STAT and the MAPK pathways.
      IL-6R expressing cells can cleave the receptor protein to generate a soluble IL
      6R (sIL-6R), which can still bind IL-6 and can associate with gp130 and induce
      signaling even on cells, which do not express IL-6R. This paradigm has been
      called IL-6 trans-signaling whereas signaling via the membrane bound IL-6R is
      referred to as classic signaling. We have generated several molecular tools to
      differentiate between IL-6 classic- and trans-signaling and to analyze the
      consequence of cellular IL-6 signaling in vivo.

PMID- 29322415
TI  - Laser Microdissection of Cellular Compartments for Expression Analyses in Cancer
      Models.
AB  - Cancer tissues are composed of various cell types including cancer cells, cancer
      associated fibroblasts (CAFs), tumor-associated macrophages (TAMs) and
      endothelial cells. These surrounding stromal cells form the tumor
      microenvironment, partly through the inflammatory response, which plays an
      important role in the development and malignant progression of cancer. It is
      therefore important to examine the expression profiles and protein modifications
      of each cellular component independently to decipher the interaction between the
      tumor cells and the microenvironment. We herein describe a protocol for laser
      microdissection, which allows for the individual cellular compartments to be
      collected separately. This will allow us to perform real-time RT-PCRs and
      microarray analyses of specific cell types in tumor tissues.

PMID- 29322416
TI  - Tissue Processing for Stereological Analyses of Lung Structure in Chronic
      Obstructive Pulmonary Disease.
AB  - Quantitative data on lung structure, such as volume, surface area and length, are
      used for assessment of the functional performance of the lung during normal
      development and inflammatory-related diseases such as chronic obstructive
      pulmonary disorder (COPD), and carcinogenesis, in animal models. Stereology is
      considered as the gold standard to obtain quantitative data on lung structure,
      with a key advantage being to quantify irregular three-dimensional structures on
      the basis of measurement made on two-dimensional sections. Therefore,
      preservation of original tissue dimensions without shrinkage is vital for
      stereology.Three steps, fixation, sampling and embedding, are essential
      requirements to minimise tissue shrinkage to obtain theoretically unbiased
      estimates of stereological parameters of lung structures. Perfusion fixation by
      intratracheal instillation with 1.5% glutaraldehyde/1.5% formaldehyde at a
      pressure of 25 cm fluid column is considered as one of the best methods. A
      systematic uniform random sampling scheme is then applied to the fixed lung to
      ensure each and every part of the lung is analysed, irrespective of homogeneity
      or heterogeneity of the structural distribution. The sampled tissue sections are
      then embedded in glycol methacrylate to minimise further tissue shrinkage. Here
      we describe the accurate fixation, sampling and embedding for stereological
      methods to quantify lung structures in mice.

PMID- 29322417
TI  - Quantifying Caspase-1 Activity in Murine Macrophages.
AB  - The caspase-1 protease is a core component of multiprotein inflammasome
      complexes, which play a critical role in regulating the secretion of mature,
      bioactive pro-inflammatory cytokines interleukin (IL)-1beta and IL-18. The
      activity of caspase-1 is often measured indirectly, by monitoring cleavage of
      cellular caspase-1 substrates, processing of caspase-1 itself, or by quantifying
      cell death. Here we describe methods for eliciting caspase-1 activity in murine
      macrophages, via activation of the NLRP3, NAIP/NLRC4 or AIM2 inflammasomes. We
      then describe a simple fluorogenic assay for directly quantifying cellular
      caspase-1 activity.

PMID- 29322418
TI  - Analysis of Histone Modifications in Acute Myeloid Leukaemia Using Chromatin
      Immunoprecipitation.
AB  - Chromatin Immunoprecipitation (ChIP) using antibodies specific for histone
      modifications is a powerful technique for assessing the epigenetic states of cell
      populations by either quantitative PCR (ChIP-PCR) or next generation sequencing
      analysis (ChIP-Seq). Here we describe the procedure for ChIP of histone marks in
      myeloid leukaemia cell lines and the subsequent purification of genomic DNA
      associated with repressive and activating histone modifications for further
      analysis. This procedure can be widely applied to a variety of histone marks to
      assess both activating and repressive modifications in the context of myeloid
      leukaemia.

PMID- 29322419
TI  - Analysis of DNA Methylation in Tissues Exposed to Inflammation.
AB  - Induction of aberrant DNA methylation is one of the most important mechanisms
      mediating the effect of inflammation on cancer development. Aberrant methylation
      of promoter CpG islands of tumor suppressor genes can silence their downstream
      genes, and that in cancer tissues is associated with prognosis or therapeutic
      effects. In addition, aberrant methylation can occur in tissues exposed to
      specific types of inflammation, producing a so-called "epigenetic field for
      cancerization," and its accumulation is correlated with cancer risk. Thus,
      aberrant methylation at specific loci is an important biomarker and mediator of
      the carcinogenic effect of inflammation. DNA methylation at specific genomic
      regions can be analyzed by various methods based upon bisulfite-mediated DNA
      conversion, which specifically converts unmethylated cytosines into uracils under
      appropriate conditions. Methylation-specific PCR (MSP), quantitative MSP, and
      bisulfite sequencing are widely used, and this chapter provides protocols for
      bisulfite-mediated conversion, quantitative MSP, and bisulfite sequencing.

PMID- 29322420
TI  - A Comprehensive Protocol Resource for Performing Pooled shRNA and CRISPR Screens.
AB  - This chapter details a compendium of protocols that collectively enable the
      reader to perform a pooled shRNA and/or CRISPR screen-with methods to identify
      and validate positive controls and subsequent hits; establish a viral titer in
      the cell line of choice; create and screen libraries, sequence strategies, and
      bioinformatics resources to analyze outcomes. Collectively, this provides an
      overarching resource from the start to finish of a screening project, making this
      technology possible in all laboratories.

PMID- 29322421
TI  - Immuno-detection of Immature and Bioactive Forms of the Inflammatory Cytokine IL
      18.
AB  - Gastric cancer (GC) is the third most lethal cancer worldwide, and like many
      other types of cancers, it is associated with precursory chronic inflammatory
      responses. In the context of many inflammation-associated cancers such as GC,
      activation of the innate immune response by infectious microbes and/or host
      derived molecules is often characterized by production of the cytokines
      interleukin (IL)-1beta and IL-18, which can often have divergent and opposing
      (i.e., pro or anti) roles in inflammation and oncogenesis. The processing of
      these mature bioactive cytokines from their inactive precursor polypeptides is
      dependent upon the enzyme Caspase-1, which is part of multiprotein complexes
      called "inflammasomes." Considering the recent mounting evidence for the role of
      IL-18 in the pathogenesis of GC, here, we describe a Western blotting technique
      used on genetic mouse models for GC to detect and characterize both pro-Il-18 and
      mature IL-18 proteins.

PMID- 29322422
TI  - Optimization Techniques for miRNA Expression in Low Frequency Immune Cell
      Populations.
AB  - In this chapter we outline a RNA extraction method for very low immune cell
      populations isolated from the central nervous system of mice undergoing
      experimental autoimmune encephalomyelitis. We compare various normalization and
      quantification techniques to examine miRNA expression. Our data highlight that
      employing a mean normalization procedure using a number of well-selected
      housekeeping miRNA genes, followed by absolute quantification with a standard
      curve generated from a commercial miRNA oligo, gave the most robust and
      reproducible miRNA expression results.

PMID- 29322423
TI  - Assessing the cGAS-cGAMP-STING Activity of Cancer Cells.
AB  - DNA sensing by the STING pathway is emerging to be a crucial component of the
      antitumor immune response. Although it plays a key role in the activation of
      tumor immune cells, exactly how STING is activated by tumor cells is not fully
      understood. Recent evidence suggests that cGAS can be directly engaged and
      produces 2'3'-cyclic-GMP-AMP (cGAMP) within certain tumor cells upon stimulation
      with DNA damaging agents. Because cGAMP can transfer between adjacent cells, the
      capacity of tumor cells to produce cGAMP may activate tumor immune cells, even in
      the absence of functional STING signaling within the tumor. Here we describe a
      simple coculture protocol allowing for the functional characterization of
      cGAS/STING activity in tumor cells, together with cGAMP transfer to adjacent
      cells. This approach will help define how different tumors engage the STING
      pathway, and whether synthetic STING agonists should be used to potentiate the
      antitumor effects of chemotherapies.

PMID- 29322424
TI  - Expression and Purification of JAK1 and SOCS1 for Structural and Biochemical
      Studies.
AB  - Interferon gamma (IFNgamma) is a potent inflammatory and immune cytokine.
      IFNgamma signals via the interferon gamma receptor (IFNGR), which is
      constitutively bound to Janus Kinase (JAK) 1 and JAK2 via its intracellular
      domain. These two JAK proteins then initiate the inflammatory signaling cascade.
      The most potent inhibitor of IFNgamma signaling is Suppressor of Cytokine
      Signaling 1 (SOCS1). SOCS1 negatively regulates IFNgamma signaling pathway (and
      other pathways) by directly inhibiting JAKs. Here, we describe a protocol for the
      recombinant production and purification of the JAK1 kinase domain and its
      inhibitor SOCS1, for structural and biochemical studies.

PMID- 29322425
TI  - Production of Recombinant Killer Immunoglobulin-Like Receptors for
      Crystallography and Luminex-Based Assays.
AB  - The killer immunoglobulin-like receptors (KIR) are a highly diverse family of
      cell-surface receptors that are of importance to the effector function of Natural
      Killer cells. KIR have been implicated in the detection and clearance of
      malignantly transformed cells and in the immune-control of viruses including HIV,
      HCV and CMV. Recently, the mismatching of donor and recipient KIR has been
      demonstrated to improve success of hematopoietic stem cell transplantation
      treatments of leukemias. Due to the high degree of diversity amongst the KIR, a
      number of strategies are required for the production of recombinant protein for
      medical, biochemical and structural applications. Each of these strategies has
      advantages and limitations and is suitable for different subsets of the KIR and
      their intended use. Here we describe the preparation of these proteins for
      crystallography and the novel adaptation of tetramer production for this protein
      family that is suitable for a number of assays including single-antigen bead
      binding by Luminex. These methods are intended to provide comprehensive details
      for the production and characterization of each KIR and to be broadly applicable
      to other cell surface receptors of the immune system.

PMID- 29322426
TI  - Isolation and Characterization of Mouse Intrahepatic Lymphocytes by Flow
      Cytometry.
AB  - In the field of cellular immunology multicolor flow cytometry is a frequently
      applied method that allows for the simultaneously detection of multiple
      parameters on an individual cell basis. Flow cytometry can be used to
      characterize a wide range of immune cell subsets using fluorophore-conjugated
      antibodies to a wide range of cellular antigens. The isolation of immune cells
      from nonlymphoid tissue and their preparation for flow cytometry can be a
      challenging process with respect to immune cell yields and viability. Here we
      describe a method for the efficient isolation of viable mouse intrahepatic
      lymphocytes (IHL) from normal liver tissue and liver cancer and their subsequent
      characterization by multicolor flow cytometry.

PMID- 29322427
TI  - Immunophenotyping of pediatric brain tumors: correlating immune infiltrate with
      histology, mutational load, and survival and assessing clonal T cell response.
AB  - There is little known regarding the immune infiltrate present in pediatric brain
      tumors and how this compares to what is known about histologically similar adult
      tumors and its correlation with survival. Here, we provide a descriptive analysis
      of the immune infiltrate of 22 fresh pediatric brain tumor tissue samples of
      mixed diagnoses and 40 peripheral blood samples. Samples were analyzed using a
      flow cytometry panel containing markers for immune cell subtypes, costimulatory
      markers, inhibitory signals, and markers of activation. This was compared to the
      standard method of immunohistochemistry (IHC) for immune markers for 89 primary
      pediatric brain tumors. Both flow cytometry and IHC data did not correlate with
      the grade of tumor or mutational load and IHC data was not significantly
      associated with survival for either low grade or high grade gliomas. There is a
      trend towards a more immunosuppressive phenotype in higher grade tumors with more
      regulatory T cells present in these tumor types. Both PD1 and PDL1 were present
      in only a small percentage of the tumor infiltrate. T cell receptor sequencing
      revealed up to 10% clonality of T cells in tumor infiltrates and no significant
      difference in clonality between low and high grade gliomas. We have shown the
      immune infiltrate of pediatric brain tumors does not appear to correlate with
      grade or survival for a small sample of patients. Further research and larger
      studies are needed to fully understand the interaction of pediatric brain tumors
      and the immune system.

PMID- 29322428
TI  - Feasibility of the evidence-based cognitive telerehabilitation program Remind for
      patients with primary brain tumors.
AB  - Many patients with primary brain tumors experience cognitive deficits. Cognitive
      rehabilitation programs focus on alleviating these deficits, but availability of
      such programs is limited. Our large randomized controlled trial (RCT)
      demonstrated positive effects of the cognitive rehabilitation program developed
      by our group. We converted the program into the iPad-based cognitive
      rehabilitation program ReMind, to increase its accessibility. The app
      incorporates psychoeducation, strategy training and retraining. This pilot study
      in patients with primary brain tumors evaluates the feasibility of the use of the
      ReMind-app in a clinical (research) setting in terms of accrual, attrition,
      adherence and patient satisfaction. The intervention commenced 3 months after
      resective surgery and patients were advised to spend 3 h per week on the program
      for 10 weeks. Of 28 eligible patients, 15 patients with presumed low-grade glioma
      or meningioma provided informed consent. Most important reason for decline was
      that patients (7) experienced no cognitive complaints. Participants completed on
      average 71% of the strategy training and 76% of the retraining. Some patients
      evaluated the retraining as too easy. Overall, 85% of the patients evaluated the
      intervention as "good" or "excellent". All patients indicated that they would
      recommend the program to other patients with brain tumors. The ReMind-app is the
      first evidence-based cognitive telerehabilitation program for adult patients with
      brain tumors and this pilot study suggests that postoperative cognitive
      rehabilitation via this app is feasible. Based on patients' feedback, we have
      expanded the retraining with more difficult exercises. We will evaluate the
      efficacy of ReMind in an RCT.

PMID- 29322429
TI  - Comment on "Serum Hepcidin and Soluble Transferrin Receptor in the Assessment of
      Iron Metabolism in Children on a Vegetarian Diet".

PMID- 29322430
TI  - Serum Copper Homeostasis in Hypertensive Intracerebral Hemorrhage and its
      Clinical Significance.
AB  - This study was to investigate the alterations of serum copper homeostasis after
      hypertensive intracerebral hemorrhage (ICH), which is not yet clear. We recruited
      85 hypertensive ICH patients and determined their serum levels of total copper
      (TCu), small molecule copper (SMC), and ceruloplasmin (Cp). Sera from 32 healthy
      persons and 12 primary hypertension patients were collected and analyzed as well.
      Serum TCu levels in ICH patients were tested at three time points (on admission,
      day 3, and day 7) and found to be higher than that in hypertension patients (p <
      0.05). The serum SMC levels in hypertension patients and ICH patients at three
      time points were higher than that in healthy controls (p < 0.05). Higher serum
      SMC levels on days 3 and 7 were associated with death in the hospital.
      Additionally, higher serum SMC levels on the seventh day were associated with
      poor outcome at discharge. High serum Cp levels on admission, as well as low
      serum Cp levels on the seventh day, were associated with death in the hospital (p
      = 0.002 and p = 0.034, respectively). Our findings indicated that declines in
      serum Cp and increases in serum SMC are correlated with lethal or poor outcome in
      hypertensive ICH patients, possibly as a result of contributions to secondary
      injury of brain after hemorrhage due to impairment of iron transport and enhanced
      oxidative stress.

PMID- 29322431
TI  - Daylight Photodynamic Therapy Versus 5-Fluorouracil for the Treatment of Actinic
      Keratosis: A Case Series.
AB  - INTRODUCTION: The incidence of actinic keratosis (AK) continues to increase
      worldwide. Currently available options for the treatment of AK include topical 5
      fluorouracil (5-FU) and daylight-mediated photodynamic therapy (DL-PDT). This
      split-face pilot study compared DL-PDT using 16% methyl aminolevulinate (MAL)
      cream versus 5-FU cream in patients with AK on the face/scalp. METHODS: Five male
      subjects (mean age 70 years) with grade I-III AK on the face/scalp were enrolled.
      Subjects received a single session of DL-PDT with 16% MAL on one side and topical
      5% 5-FU for 21 days on the other side. Evaluations of efficacy, safety, and
      subject satisfaction were conducted 48 h, 7 days, 14 days, 1 month, and 3 months
      after treatment. RESULTS: At 3 months, the lesion complete response rate was 80%
      and 93% for DL-PDT and 5-FU, respectively. Lesion partial response was 20% and
      7%, respectively. Fewer treatment-related adverse events (AEs) were reported with
      DL-PDT than with 5-FU, and they resolved spontaneously in 5-7 and 27-30 days,
      respectively. Subjects preferred DL-PDT because of the lower incidence of AEs and
      rapid recovery compared with 5-FU. CONCLUSION: DL-PDT is a convenient alternative
      to 5-FU with good efficacy and a favorable safety profile, allowing patients to
      effectively treat their AK without compromising their social life. FUNDING:
      Galderma.

PMID- 29322432
TI  - Renal histopathological findings of retinal vasculopathy with cerebral
      leukodystrophy.
AB  - Retinal vasculopathy with cerebral leukodystrophy (RVCL) is a rare autosomal
      dominant systemic microvascular disease. Neurological disorders and visual
      disturbance are highlighted as manifestations of RVCL; however, there are few
      reports focused on nephropathy. Herein, we describe detailed renal
      histopathological findings in a daughter and father with RVCL, proven by TREX1
      genetic analysis. A kidney biopsy of the daughter, 35-year-old with asymptomatic
      proteinuria, revealed unique and various glomerular changes. Atypical double
      contour (not tram track-like) of the capillary wall was widely found, an apparent
      characteristic finding. Glomerular findings were varied due to a combination of
      new and old segmental mesangial proliferative changes, mesangiolysis, and
      segmental glomerulosclerosis-like lesions; these changes may be related to
      endothelial cell damage. Collapsed tufts were also found and thought to be the
      result of ischemia due to arterial changes. Glomerular findings in a kidney
      biopsy of the father revealed similarity to the daughter's glomerulus at a
      relatively advanced stage, but the degree of variety in the glomerular findings
      was much less. Kidney biopsy findings suggesting endothelial cell damage of
      unknown etiology need to be considered for possible RVCL.

PMID- 29322433
TI  - Biological aortic valve replacement: advantages and optimal indications of
      stentless compared to stented valve substitutes. A review.
AB  - Controversy still surrounds the optimal biological valve substitute for aortic
      valve replacement. In light of the current literature, we review advantages and
      optimal indications of stentless compared to stented aortic bio-prostheses.
      Recent meta-analyses, prospective randomized controlled trials and retrospective
      studies comparing the most frequently used stentless and stented aortic bio
      prostheses were analyzed. In the present review, the types and implantation
      techniques of the bio-prosthesis that are seldom taken into account by most
      studies and reviews were integrated in the interpretation of the relevant
      reports. For stentless aortic root bio-prostheses, full-root vs. sub-coronary
      implantation offered better early transvalvular gradients, effective orifice area
      and left ventricular mass regression as well as late freedom from structural
      valve deterioration in retrospective studies. Early mortality and morbidity did
      not differ between the stentless and stented aortic bio-prostheses. Early
      transvalvular gradients, effective orifice area and regression of left
      ventricular hypertrophy were significantly better for stentless, especially as
      full-root, compared to stented bio-prostheses. The long-term valve-related
      survival for stentless aortic root and Toronto SPV bio-prosthesis was as good as
      that for stented pericardial aortic bio-prostheses. For full-root configuration
      this survival advantage was statistically significant. There seems to be not one
      but different ideal biological valve substitutes for different subgroups of
      patients. In patients with small aortic root or exposed to prosthesis-patient
      mismatch full-root implantation of stentless bio-prostheses may better meet
      functional needs of individual patients. Longer follow-ups on newer generation of
      stented bio-prostheses are needed for comparison of their hemodynamic performance
      with stentless counterparts especially in full-root configuration.

PMID- 29322434
TI  - Protection from Reperfusion Injury with Intracoronary N-Acetylcysteine in
      Patients with STEMI Undergoing Primary Percutaneous Coronary Intervention in a
      Cardiac Tertiary Center.
AB  - BACKGROUND: Evidence suggests that oxidative stress plays a principal role in
      myocardial damage following ischemia/reperfusion events. Recent studies have
      shown that the antioxidant properties of N-acetylcysteine (NAC) may have
      cardioprotective effects in high doses, but-to the best of our knowledge-few
      studies have assessed this. OBJECTIVES: Our objective was to investigate the
      impact of high-dose NAC on ischemia/reperfusion injury. METHODS: We conducted a
      randomized double-blind placebo-controlled trial in which 100 consecutive
      patients with ST-elevation myocardial infarction undergoing percutaneous coronary
      intervention (PCI) were randomly assigned to the case group (high-dose NAC 100
      mg/kg bolus followed by intracoronary NAC 480 mg during PCI then intravenous NAC
      10 mg/kg for 12 h) or the control group (5% dextrose). We measured differences in
      peak creatine kinase-myocardial band (CK-MB) concentration, highly sensitive
      troponin T (hs-TnT), thrombolysis in myocardial infarction (TIMI) flow,
      myocardial blush grade (MBG), and corrected thrombolysis in myocardial infarction
      frame count (cTFC). RESULTS: The peak CK-MB level was comparable between the two
      groups (P = 0.327), but patients receiving high-dose NAC demonstrated a
      significantly larger reduction in hs-TnT (P = 0.02). In total, 94% of the NAC
      group achieved TIMI flow grade 3 versus 80% of the control group (P = 0.03). No
      significant differences were observed between the two groups in terms of changes
      in the cTFC and MBG. CONCLUSIONS: In this study, NAC improved myocardial
      reperfusion markers and coronary blood flow, as revealed by differences in peak
      hs-TnT and TIMI flow grade 3 levels, respectively. Further studies with large
      samples are warranted to elucidate the role of NAC in this population.
      ClinicalTrials.gov identifier: NCT01741207, and the Iranian Registry of Clinical
      Trials (IRCT; http://irct.ir ) registration number: IRCT201301048698N8.

PMID- 29322435
TI  - Vaccine-associated paralytic poliomyelitis in a patient with acute lymphocytic
      leukemia.
AB  - We report a case of vaccine-associated paralytic poliomyelitis (VAPP) in an
      immunocompromised patient with acute lymphocytic leukemia who was initially
      diagnosed with aseptic meningitis. Isolation of Sabin-like type 1 poliovirus from
      the patient's cerebrospinal fluid made this a case of vaccine-related poliovirus
      (VRPV) infection. The patient developed paralysis and respiratory distress and
      deceased a few months after onset of paralysis with respiratory failure. This
      tragic case report highlights the emergence of VAPP and indicates the importance
      of timely diagnosis of VRPV infections to improve clinical management of VRPV
      infected patients and to prevent the devastating consequences of silent
      introduction of VRPVs in treatment wards and eventually in the society.

PMID- 29322436
TI  - Detection and Reconstruction of Circular RNAs from Transcriptomic Data.
AB  - Recent studies have shown that circular RNAs (circRNAs) are a novel class of
      abundant, stable, and ubiquitous noncoding RNA molecules in eukaryotic organisms.
      Comprehensive detection and reconstruction of circRNAs from high-throughput
      transcriptome data is an initial step to study their biogenesis and function.
      Several tools have been developed to deal with this issue, but they require many
      steps and are difficult to use. To solve this problem, we provide a protocol for
      researchers to detect and reconstruct circRNA by employing CIRI2, CIRI-AS, and
      CIRI-full. This protocol can not only simplify the usage of above tools but also
      integrate their results.

PMID- 29322437
TI  - Deep Computational Circular RNA Analytics from RNA-seq Data.
AB  - Circular RNAs (circRNAs) have been first described as "scrambled exons" in the
      1990s. CircRNAs originate from back splicing or exon skipping of linear RNA
      templates and have continuously gained attention in recent years due to the
      availability of high-throughput whole-transcriptome sequencing methods. Numerous
      manuscripts describe thousands of circRNAs throughout uni- and multicellular
      eukaryote species and demonstrated that they are conserved, stable, and abundant
      in specific tissues or conditions. This manuscript provides a walk-through of our
      bioinformatics toolbox, which covers all aspects of in silico circRNA analysis,
      starting from raw sequencing data and back-splicing junction discovery to circRNA
      quantitation and reconstruction of internal the circRNA structure.

PMID- 29322438
TI  - Genome-Wide circRNA Profiling from RNA-seq Data.
AB  - The genome-wide expression patterns of circular RNAs (circRNAs) are of increasing
      interest for their potential roles in normal cellular homeostasis, development,
      and disease. Thousands of circRNAs have been annotated from various species in
      recent years. Analysis of publically available or user-generated rRNA-depleted
      total RNA-seq data can be performed to uncover new circRNA expression trends.
      Here we provide a primer for profiling circRNAs from RNA-seq datasets. The
      description is tailored for the wet lab scientist with limited or no experience
      in analyzing RNA-seq data. We begin by describing how to access and interpret
      circRNA annotations. Next, we cover converting circRNA annotations into junction
      sequences that are used as scaffolds to align RNA-seq reads. Lastly, we visit
      quantifying circRNA expression trends from the alignment data.

PMID- 29322439
TI  - Analysis of Circular RNAs Using the Web Tool CircInteractome.
AB  - Circular RNAs (circRNAs) are generated through nonlinear back splicing, during
      which the 5' and 3' ends are covalently joined. Consequently, the lack of free
      ends makes them very stable compared to their counterpart linear RNAs. By
      selectively interacting with microRNAs and RNA-binding proteins (RBPs), circRNAs
      have been shown to influence gene expression programs. We designed a web tool,
      CircInteractome, in order to (1) explore potential interactions of circRNAs with
      RBPs, (2) design specific divergent primers to detect circRNAs, (3) study tissue-
      and cell-specific circRNAs, (4) identify gene-specific circRNAs, (5) explore
      potential miRNAs interacting with circRNAs, and (6) design specific siRNAs to
      silence circRNAs. Here, we review the CircInteractome tool and explain recent
      updates to the site. The database is freely accessible at
      http://circinteractome.nia.nih.gov .

PMID- 29322440
TI  - Characterization and Validation of Circular RNA and Their Host Gene mRNA
      Expression Using PCR.
AB  - Polymerase chain reaction enables the detection and characterization of circular
      RNA expression. The use of divergent primer pairs flanking the back-splice site,
      being the unique sequence element of a circular RNA, enables the detection of
      circular RNA expression. Here we describe the basic techniques to detect
      different circular transcripts of a gene or one circular RNA specifically by PCR
      and highlight the advantages and drawbacks of both.

PMID- 29322441
TI  - Detecting Circular RNAs by RNA Fluorescence In Situ Hybridization.
AB  - Fluorescence in situ hybridization (FISH) coupled to high-resolution microscopy
      is a powerful method for analyzing the subcellular localization of RNA. However,
      the detection of circular RNAs (circRNAs) using microscopy is challenging because
      the only feature of a circRNA that can be used for the probe design is its
      junction. Circular RNAs are expressed at varying levels, and for their efficient
      monitoring by FISH, background fluorescence levels need to be kept low. Here, we
      describe a FISH protocol coupled to high-precision localizations using a single
      fluorescently labeled probe spanning the circRNA junction; this allows circRNA
      detection in mammalian cells with high signal-to-noise ratios.

PMID- 29322442
TI  - Single-Molecule Fluorescence In Situ Hybridization (FISH) of Circular RNA CDR1as.
AB  - Individual mRNA molecules can be imaged in fixed cells by hybridization with
      multiple, singly labeled oligonucleotide probes, followed by computational
      identification of fluorescent signals. This approach, called single-molecule RNA
      fluorescence in situ hybridization (smRNA FISH), allows subcellular localization
      and absolute quantification of RNA molecules in individual cells. Here, we
      describe a simple smRNA FISH protocol for two-color imaging of a circular RNA,
      CDR1as, simultaneously with an unrelated messenger RNA. The protocol can be
      adapted to circRNAs that coexist with overlapping, noncircular mRNA isoforms
      produced from the same genetic locus.

PMID- 29322444
TI  - Constructing GFP-Based Reporter to Study Back Splicing and Translation of
      Circular RNA.
AB  - Human transcriptome contains a large number of circular RNAs (circRNAs) that are
      mainly produced by back splicing of pre-mRNA. Here we describe a minigene
      reporter system containing a single exon encoding split GFP in reverse order,
      which can be efficiently back spliced to produce a circRNA encoding intact GFP
      gene. This simple reporter system can be adopted to study how different cis
      elements and trans-factors affect circRNA production, and also can serve as a
      reliable system to measure the activity of IRES-mediated translation. Therefore
      this system can serve as a platform for mechanistic studies on the circRNA
      biogenesis and its function.

PMID- 29322443
TI  - A Highly Efficient Strategy for Overexpressing circRNAs.
AB  - Circular RNAs (circRNAs) constitute an emerging class of widespread, abundant,
      and evolutionarily conserved noncoding RNA. They play important and diverse roles
      in cell development, growth, and tumorigenesis, but functions of the majority of
      circRNAs remain enigmatic. In order to investigate circRNA function it is
      necessary to manipulate its expression. While various standard approaches exist
      for circRNA knockdown, here we present cloning vectors for simplifying the
      laborious process of cloning circRNAs to achieve high-efficiency overexpression
      in mammalian cell lines.

PMID- 29322445
TI  - Northern Blot Analysis of Circular RNAs.
AB  - Northern blotting enables the specific detection and characterization of RNA
      molecules. Recently, circular RNAs (circRNAs) were described as a new class of
      cell type-specific noncoding RNAs. With the discovery of many novel circRNAs on
      the basis of high-throughput sequencing and bioinformatics, a solid biochemical
      approach is required to directly detect and validate specific circRNA species.
      Here we give a detailed overview of how different Northern blot methods can be
      employed to validate specific circRNAs. Different Northern gel and detection
      systems are introduced, in combination with additional tools for circRNA
      characterization, such as RNase R and RNase H treatments.

PMID- 29322446
TI  - Nonradioactive Northern Blot of circRNAs.
AB  - Circular RNAs (circRNAs) are recognized as a special species of transcripts in
      metazoans with increasing studies, and northern blotting is a direct way to
      confirm the existence and to evaluate the size of individual circRNAs. Northern
      blotting probes can be radioactive isotope (32P) labeled, which is not
      environment-friendly and sometimes inconvenient to use. Here, we describe a
      nonradioactive northern blot protocol with digoxigenin-labeled probe to detect
      circRNA.

PMID- 29322447
TI  - Characterization of Circular RNA Concatemers.
AB  - Circular RNAs (circRNAs) constitute a novel subset in the fascinating world of
      noncoding RNA, and they are found in practically all eukaryotes. Most of them
      exhibit low expression levels but some are extremely abundant. Typically,
      circRNAs are studied by RT-PCR-based assays, but for certain types of analyses
      this technique is not suitable. Circular RNA with repetitive exons (circular
      concatemers) has been observed by us and others when transiently expressing
      circRNAs in cells, however techniques and assays to study these species have not
      been established. Here, this chapter outlines three biochemical assays (RNase R-,
      RNase H-, and alkaline-treatment) that combined with northern blotting are useful
      to study circRNAs in general and circular RNA concatemers in particular.

PMID- 29322448
TI  - Characterization of Circular RNAs (circRNA) Associated with the Translation
      Machinery.
AB  - A substantial proportion of the currently annotated genes in eukaryotes are
      proposed to function as RNA molecules (>200 bp) with no significant protein
      coding potential, currently classified as long noncoding RNAs (lncRNA). A
      distinct subgroup of lncRNAs is circular RNAs (circRNAs), which can be easily
      identified by unique junction reads, resulting from their biogenesis. CircRNAs
      are largely cytosolic and thought to either code for micro-peptides or facilitate
      gene regulation by sequestering microRNAs (miRNAs) or RNA-binding proteins (RBPs)
      from their targets. Interrogation of the interaction of circRNAs with cellular
      macromolecular machineries could indicate their mode of action. Here, we detail a
      sucrose gradient-based method to pinpoint association of a given circRNA (or any
      transcript of interest) with distinct ribosomal fractions. This method can
      evaluate the coding potential of candidate circRNAs (or any transcript of
      interest) and its association with the translation machinery.

PMID- 29322449
TI  - Synthesis and Engineering of Circular RNAs.
AB  - Circular RNAs (circRNAs) have been discovered in all kingdoms of life. They are
      produced from introns as well as from exons. However, strongest interest is in
      circRNAs that are transcribed and spliced from exons of protein and noncoding
      genes in eukaryotic cells including humans. Therefore, synthesis and engineering
      of circRNAs as models for structure and function studies are strongly required.
      In vitro, methods for RNA synthesis and circularization are available. Chemical
      synthesis allows for preparation of RNAs incorporating nonnatural nucleotides in
      small RNA segments, whereas enzymatic synthesis is advantageous for production of
      long RNAs, however, without the possibility for site-specific modification.
      Strategies for chemical and enzymatic RNA synthesis may be combined to obtain
      long modified linear RNA strands for subsequent circularization. Here, we
      describe two alternative protocols for synthesis and circularization in
      dependence on downstream applications and template structure.

PMID- 29322450
TI  - Preparation of Circular RNA In Vitro.
AB  - This chapter describes a simple and straightforward way to obtain single-stranded
      circular RNA sequences in vitro. Linear RNA that is phosphorylated at the 5' end
      is first prepared by a chemical or enzymatic method, then circularized using
      ligase. The function of the prepared circular RNA molecule, such as an ability to
      induce translation, can then be investigated.

PMID- 29322451
TI  - Discovering circRNA-microRNA Interactions from CLIP-Seq Data.
AB  - Circular RNAs (circRNAs) represent an abundant group of noncoding RNAs in
      eukaryotes and are emerging as important regulatory molecules in physiological
      and pathological processes. However, the precise mechanisms and functions of most
      of circRNAs remain largely unknown. In this chapter, we describe how to identify
      circRNA-microRNA interactions from Argonaute (AGO) cross-linking and
      immunoprecipitation followed by sequencing (CLIP-Seq) and RNA-Seq data using
      starBase platform and software. We developed three stand-alone computational
      software, including circSeeker, circAnno, and clipSearch, to identify and
      annotate circRNAs and their interactions with microRNAs (miRNAs). In addition, we
      developed interactive Web applications to evaluate circRNA-miRNA interactions
      identified from CLIP-Seq data and discover the miRNA-sponge circRNAs. starBase
      platform provides a genome browser to comparatively analyze these interactions at
      multiple levels. As a means of comprehensively integrating CLIP-Seq and RNA-Seq
      data, starBase platform is expected to reveal the regulatory networks involving
      miRNAs and circRNAs. The software and platform are available at
      http://starbase.sysu.edu.cn/circTools.php.

PMID- 29322452
TI  - Identification of circRNAs for miRNA Targets by Argonaute2 RNA
      Immunoprecipitation and Luciferase Screening Assays.
AB  - Circular RNAs from back-spliced exons (circRNAs) represent a novel class of
      widespread and endogenous RNAs in eukaryotes. circRNAs may bind to microRNAs
      (miRNAs) and inhibit the activity of miRNAs. Alternatively, miRNAs could also
      directly target circRNAs and regulate the expression of circRNAs. Here we
      describe the Argonaute2 (AGO2) RNA immunoprecipitation (RIP) and luciferase
      screening assays to identify the interaction between circRNAs and miRNAs. The
      AGO2 RIP assay evaluates the potential of the interaction between circRNAs and
      miRNAs. The luciferase screening assay investigates the targeting miRNAs and the
      detail binding sites for a specific circRNA.

PMID- 29322453
TI  - Mothering matters: Maternal style predicts puppies' future performance.
AB  - Bray et al. (2017, Proceedings of the National Academy of Sciences, 113(32), 9128
      9133) recently showed that maternal interactions between service dog mothers and
      their puppies were predictive of puppies' future success as a candidate service
      dog. These findings prompt questions into the role of genetics and early
      experiences and may provide useful selection tools for working dog breeding
      programs.

PMID- 29322454
TI  - Methods for Measuring the Production of Quorum Sensing Signal Molecules.
AB  - One relevant aspect for understanding the bottlenecks that modulate the spread of
      resistance among bacterial pathogens consists in the effect that the acquisition
      of resistance may have on the microbial physiology . Whereas studies on the
      effect of acquiring resistance of bacterial growth are frequently performed, more
      detailed analyses aiming to understand in depth the cross talk between resistance
      and virulence, including bacterial communication are less frequent. The bacterial
      quorum sensing system, is an important intraspecific and interspecific
      communication system highly relevant for many physiological processes, including
      virulence and bacterial/host interactions. Some works have shown that the
      acquisition of antibiotic resistance may impair the quorum sensing response. In
      addition, some antibiotics as antimicrobial peptides can affect the production
      and accumulation of the quorum sensing signal molecules. Given the relevance that
      this system has in the bacterial behavior in the human host, it is important to
      study the effect that the acquisition of antibiotic resistance may have on the
      production of quorum sensing signals. In this chapter we present a set of methods
      for measuring quorum sensing signals based on the use of biosensor strains,
      either coupled to Thin Layer Chromatography or for performing automated
      luminometry/spectrophotometry assays. We use Pseudomonas aeruginosa as bacterial
      model because it has a complex quorum system than encloses different signals.
      Namely, P. aeruginosa quorum sensing system consists in three different
      interconnected regulatory networks, each one presenting a specific autoinducer
      molecule: the las system, which signal is N-(3-oxo-dodecanoyl)-L-homoserine
      lactone, the rhl system, which signal is N-butanoyl-homoserine lactone and the
      pqs system, which signals are 2-heptyl-3-hydroxy-4(1H)-quinolone together with
      its immediate precursor 2-heptyl-4-hydroxy-quinoline.

PMID- 29322455
TI  - Construction and Use of Staphylococcus aureus Strains to Study Within-Host
      Infection Dynamics.
AB  - The study of the dynamics that occur during the course of a bacterial infection
      has been attempted using several methods. Here we discuss the construction of a
      set of antibiotic-resistant, otherwise-isogenic Staphylococcus aureus strains
      that can be used to observe the progress of systemic disease in a mouse model at
      various time-points postinfection. The strains can likewise be used to study the
      progression of infection in other animal infection models, such as the zebrafish
      embryo. Furthermore, the use of antibiotic resistance tags provides a convenient
      system with which to investigate the effect of antimicrobial chemotherapy during
      disease.

PMID- 29322456
TI  - Method for Detecting and Studying Genome-Wide Mutations in Single Living Cells in
      Real Time.
AB  - DNA sequencing and fluctuation test have been choice methods for studying DNA
      mutations for decades. Although invaluable tools allowing many important
      discoveries on mutations, they are both highly influenced by fitness effects of
      mutations, and therefore suffer several limits. Fluctuation test is for example
      limited to mutations that produce an identifiable phenotype, which is the
      minority of all generated mutations. Genome-wide extrapolations using this method
      are therefore difficult. DNA sequencing detects almost all DNA mutations in
      population of cells. However, the obtained population mutation spectrum is biased
      because of the fitness effects of newly generated mutations. For example,
      mutations that affect fitness strongly and negatively are underrepresented, while
      those with a strong positive effect are overrepresented. Single-cell genome
      sequencing can solve this problem. However, sufficient amount of DNA for this
      approach is obtained by massive whole-genome amplification, which produces many
      artifacts.We describe the first direct method for monitoring genome-wide
      mutations in living cells independently of their effect on fitness. This method
      is based on the following three facts. First, DNA replication errors are the
      major source of DNA mutations. Second, these errors are the target for an
      evolutionarily conserved mismatch repair (MMR) system, which repairs the vast
      majority of replication errors. Third, we recently showed that the fluorescently
      labeled MMR protein MutL forms fluorescent foci on unrepaired replication errors.
      If not repaired, the new round of DNA synthesis fixes these errors in the genome
      permanently, i.e., they become mutations. Therefore, visualizing foci of the
      fluorescently tagged MutL in individual living cells allows detecting mutations
      as they appear, before the expression of the phenotype.

PMID- 29322457
TI  - Detecting Phenotypically Resistant Mycobacterium tuberculosis Using Wavelength
      Modulated Raman Spectroscopy.
AB  - Raman spectroscopy is a non-destructive and label-free technique. Wavelength
      modulated Raman (WMR) spectroscopy was applied to investigate Mycobacterium
      tuberculosis cell state, lipid rich (LR) and lipid poor (LP). Compared to LP
      cells, LR cells can be up to 40 times more resistant to key antibiotic regimens.
      Using this methodology single lipid rich (LR) from lipid poor (LP) bacteria can
      be differentiated with both high sensitivity and specificity. It can also be used
      to investigate experimentally infected frozen tissue sections where both cell
      types can be differentiated. This methodology could be utilized to study the
      phenotype of mycobacterial cells in other tissues.

PMID- 29322458
TI  - A Flow Cytometry Method for Assessing M. tuberculosis Responses to Antibiotics.
AB  - Traditional drug susceptibility methods can take several days or weeks of
      incubation between drug exposure and confirmation of sensitivity or resistance.
      In addition, these methods do not capture information about viable organisms that
      are not immediately culturable after drug exposure. Here, we present a rapid
      fluorescence detection method for assessing the susceptibility of M. tuberculosis
      to antibiotics. Fluorescent markers Calcein violet-AM and SYTOX-green are used
      for measuring cell viability or cell death and to capture information about the
      susceptibility of the whole population and not just those bacteria that can grow
      in media postexposure. Postexposure to the antibiotic, the method gives a rapid
      readout of drug susceptibility, as well as insights into the concentration and
      time-dependent drug activity following antibiotic exposure.

PMID- 29322459
TI  - Application of Continuous Culture for Assessing Antibiotic Activity Against
      Mycobacterium tuberculosis.
AB  - There is a proportion of the M. tuberculosis population that is refractory to the
      bactericidal action of antituberculosis antibiotics due to phenotypic tolerance.
      This tolerance can be impacted by environmental stimuli and the subsequent
      physiological state of the organism. It may be the result of preexisting
      populations of slow growing/non replicating bacteria that are protected from
      antibiotic action. It still remains unclear how the slow growth of M.
      tuberculosis contributes to antibiotic resistance and antibiotic tolerance. Here,
      we present a method for assessing the activity of antibiotics against M.
      tuberculosis using continuous culture, which is the only system that can be used
      to control bacterial growth rate and study the impact of slow or fast growth on
      the organism's response to antibiotic exposure.

PMID- 29322460
TI  - Real-Time Digital Bright Field Technology for Rapid Antibiotic Susceptibility
      Testing.
AB  - Optical scanning through bacterial samples and image-based analysis may provide a
      robust method for bacterial identification, fast estimation of growth rates and
      their modulation due to the presence of antimicrobial agents. Here, we describe
      an automated digital, time-lapse, bright field imaging system (oCelloScope,
      BioSense Solutions ApS, Farum, Denmark) for rapid and higher throughput
      antibiotic susceptibility testing (AST) of up to 96 bacteria-antibiotic
      combinations at a time. The imaging system consists of a digital camera, an
      illumination unit and a lens where the optical axis is tilted 6.25 degrees 
      relative to the horizontal plane of the stage. Such tilting grants more freedom
      of operation at both high and low concentrations of microorganisms. When
      considering a bacterial suspension in a microwell, the oCelloScope acquires a
      sequence of 6.25 degrees -tilted images to form an image Z-stack. The stack
      contains the best-focus image, as well as the adjacent out-of-focus images (which
      contain progressively more out-of-focus bacteria, the further the distance from
      the best-focus position). The acquisition process is repeated over time, so that
      the time-lapse sequence of best-focus images is used to generate a video. The
      setting of the experiment, image analysis and generation of time-lapse videos can
      be performed through a dedicated software (UniExplorer, BioSense Solutions ApS).
      The acquired images can be processed for online and offline quantification of
      several morphological parameters, microbial growth, and inhibition over time.

PMID- 29322461
TI  - Enhanced Methodologies for Detecting Phenotypic Resistance in Mycobacteria.
AB  - Lipid droplets found in algae and other microscopic organisms have become of
      interest to many researchers partially because they carry the capacity to produce
      bio-oil for the mass market. They are of importance in biology and clinical
      practice because their presence can be a phenotypic marker of an altered
      metabolism, including reversible resistance to antibiotics, prompting intense
      research.A useful stain for detecting lipid bodies in the lab is Nile red. It is
      a dye that exhibits solvatochromism; its absorption band varies in spectral
      position, shape and intensity with the nature of its solvent environment, it will
      fluoresce intensely red in polar environment and blue shift with the changing
      polarity of its solvent. This makes it ideal for the detection of lipid bodies
      within Mycobacterium spp. This is because mycobacterial lipid bodies' primary
      constituents are nonpolar lipids such as triacylglycerols but bacterial cell
      membranes are primarily polar lipid species. In this chapter we describe an
      optimal method for using Nile red to distinguish lipid containing (Lipid rich or
      LR cells) from those without lipid bodies (Lipid Poor or LP). As part of the
      process we have optimized a method for separating LP and LR cells that does not
      require the use of an ultracentrifuge or complex separation media. We believe
      that these methods will facilitate further research in these enigmatic, transient
      and important cell states.

PMID- 29322463
TI  - Selection of ESBL-Producing E. coli in a Mouse Intestinal Colonization Model.
AB  - Asymptomatic human carriage of antimicrobially drug-resistant pathogens prior to
      infection is increasing worldwide. Further investigation into the role of this
      fecal reservoir is important for combatting the increasing antimicrobial
      resistance problems. Additionally, the damage on the intestinal microflora due to
      antimicrobial treatment is still not fully understood. Animal models are powerful
      tools to investigate bacterial colonization subsequent to antibiotic treatment.
      In this chapter we present a mouse-intestinal colonization model designed to
      investigate how antibiotics select for an ESBL-producing E. coli isolate. The
      model can be used to study how antibiotics with varying effect on the intestinal
      flora promote the establishment of the multidrug-resistant E. coli. Colonization
      is successfully investigated by sampling and culturing stool during the days
      following administration of antibiotics. Following culturing, a precise
      identification of the bacterial strain found in mice feces is applied to ensure
      that the isolate found is in fact identical to the strain used for inoculation.
      For this purpose random amplified of polymorphic DNA (RAPD) PCR specifically
      developed for E. coli is applied. This method allows us to distinguish E. coli
      with more than 99.95% genome similarity using a duplex PCR method.

PMID- 29322462
TI  - Methods to Determine Mutational Trajectories After Experimental Evolution of
      Antibiotic Resistance.
AB  - The evolution of bacterial resistance to antibiotics by mutation within the
      genome (as distinct from horizontal gene transfer of new material into a genome)
      could occur in a single step but is usually a multistep process. Resistance
      evolution can be studied in laboratory environments by serial passage of bacteria
      in liquid culture or on agar, with selection at constant, or varying,
      concentrations of drug. Whole genome sequencing can be used to make an initial
      analysis of the evolved mutants. The trajectory of evolution can be determined by
      sequence analysis of strains from intermediate steps in the evolution,
      complemented by phenotypic analysis of genetically reconstructed isogenic strains
      that recapitulate the intermediate steps in the evolution.

PMID- 29322464
TI  - Transcriptional Profiling Mycobacterium tuberculosis from Patient Sputa.
AB  - The emergence of drug resistance threatens to destroy tuberculosis control
      programs worldwide, with resistance to all first-line drugs and most second-line
      drugs detected. Drug tolerance (or phenotypic drug resistance) is also likely to
      be clinically relevant over the 6-month long standard treatment for drug
      sensitive tuberculosis. Transcriptional profiling the response of Mycobacterium
      tuberculosis to antimicrobial drugs offers a novel interpretation of drug
      efficacy and mycobacterial drug-susceptibility that likely varies in dynamic
      microenvironments, such as the lung. This chapter describes the noninvasive
      sampling of tuberculous sputa and techniques for mRNA profiling M. tb bacilli
      during patient therapy to characterize real-world drug actions.

PMID- 29322465
TI  - Direct in Gel Genomic Detection of Antibiotic Resistance Genes in S1 Pulsed Field
      Electrophoresis Gels.
AB  - S1 pulsed field gel electrophoresis (PFGE) is a method to separate the bacterial
      chromosome(s) from plasmid nucleic acids. When combined with ethidium bromide
      staining and UV visualization this method is excellent at assessing the number of
      plasmids in individual bacterial strains. It is also good at approximating the
      true size of each individual plasmid when run against a DNA molecular marker.
      However, downstream applications such as: the location of individual resistance
      genes on individual plasmids or the chromosome are hampered by very poor transfer
      of large DNA molecules from agarose gels to adsorbent nylon or nitrocellulose
      membranes. Herein, we describe a method to directly probe agarose PFGE gels
      eliminating the necessity of transfer and generating excellent genomic location
      results.

PMID- 29322466
TI  - Using RT qPCR for Quantifying Mycobacteria marinum from In Vitro and In Vivo
      Samples.
AB  - Mycobacterium marinum, the causative agent of fish tuberculosis, is rarely a
      human pathogen causing a chronic skin infection. It is now wildely used as a
      model system in animal models, especially in zebra fish model, to study the
      pathology of tuberculosis and as a means of screening new anti-tuberculosis
      agent. To facilitate such research, quantifying the viable count of M. marinum
      bacteria is a crucial step. The main approach used currently is still by counting
      the number of colony forming units (cfu), a method that has been in place for
      almost 100 years. Though this method well established, understood and relatively
      easy to perform, it is time-consuming and labor-intensive. The result can be
      compromised by failure to grow effectively and the relationship between count and
      actual numbers is confused by clumping of the bacteria where a single colony is
      made from multiple organisms. More importantly, this method is not able to detect
      live but not cultivable bacteria, and there is increasing evidence that
      mycobacteria readily enter a "dormant" state which confounds the relationship
      between bacterial number in the host and the number detected in a cfu assay. DNA
      based PCR methods detect both living and dead organisms but here we describe a
      method, which utilizes species specific Taq-Man assay and RT-qPCR technology for
      quantifying the viable M. marinum bacterial load by detecting 16S ribosomal RNA
      (16S rRNA).

PMID- 29322467
TI  - Use of Larval Zebrafish Model to Study Within-Host Infection Dynamics.
AB  - Investigating bacterial dynamics within the infected host has proved very useful
      for understanding mechanisms of pathogenesis. Here we present the protocols we
      use to study bacterial dynamics within infected embryonic zebrafish. This chapter
      encompasses basic techniques used to study bacterial infection within larval
      zebrafish, including embryonic zebrafish maintenance, injections of morpholino
      oligonucleotides, intravenous injections of bacterial suspensions, and
      fluorescence imaging of infected zebrafish. Specific methods for studying
      bacterial within-host population dynamics are also described.

PMID- 29322468
TI  - A Method to Evaluate Persistent Mycobacterium tuberculosis In Vitro and in the
      Cornell Mouse Model of Tuberculosis.
AB  - Persistent Mycobacterium tuberculosis will not grow on solid or liquid media.
      They will, however, grow in the presence of resuscitation promoting factors
      (RPF). Here we describe the production of RPF rich culture supernatants, and
      their use for the stimulation of growth of persisters in vitro as well as in the
      Cornell model of tuberculosis.

PMID- 29322469
TI  - Removal of muscular artifacts in EEG signals: a comparison of linear
      decomposition methods.
AB  - The most common approach to reduce muscle artifacts in electroencephalographic
      signals is to linearly decompose the signals in order to separate artifactual
      from neural sources, using one of several variants of independent component
      analysis (ICA). Here we compare three of the most commonly used ICA methods
      (extended Infomax, FastICA and TDSEP) with two other linear decomposition methods
      (Fourier-ICA and spatio-spectral decomposition) suitable for the extraction of
      oscillatory activity. We evaluate the methods' ability to remove event-locked
      muscle artifacts while maintaining event-related desynchronization in data from
      18 subjects who performed self-paced foot movements. We find that all five
      analyzed methods drastically reduce the muscle artifacts. For the three ICA
      methods, adequately high-pass filtering is very important. Compared to the effect
      of high-pass filtering, differences between the five analyzed methods were small,
      with extended Infomax performing best.

PMID- 29322471
TI  - Correction to: Pharmacists' confidence when providing pharmaceutical care on
      anticoagulants, a multinational survey.
AB  - In the original publication of this article, the article note has been missed and
      published online.

PMID- 29322470
TI  - Associations between the Drug Burden Index, Potentially Inappropriate Medications
      and Quality of Life in Residential Aged Care.
AB  - BACKGROUND: Inappropriate polypharmacy may negatively impact the quality of life
      of residents in aged care facilities, but it remains unclear which medications
      may influence this reduced quality of life. OBJECTIVE: The objective of this
      study was to examine whether the Drug Burden Index and potentially inappropriate
      medications were associated with quality of life in older adults living in
      residential care with a high prevalence of cognitive impairment and dementia.
      METHODS: We conducted cross-sectional analyses of 541 individuals recruited from
      17 residential aged care facilities in Australia in the Investigating Services
      Provided in the Residential Environment for Dementia (INSPIRED) study. Quality of
      life was measured using the EuroQol Five Dimensions Questionnaire (a measure of
      generic quality of life) and the Dementia Quality of Life Questionnaire completed
      by the participant or a proxy. RESULTS: In the 100 days prior to recruitment,
      83.1% of the participants received at least one anticholinergic or sedative
      medication included in the Drug Burden Index and 73.0% received at least one
      potentially inappropriate medication according to the Beers Criteria. Multi-level
      linear models showed there was a significant association between a higher Drug
      Burden Index and lower quality of life according to the EuroQol Five Dimensions
      Questionnaire [beta (standard error): - 0.034 (0.012), p = 0.006] after
      adjustment for potential confounding factors. Increasing numbers of potentially
      inappropriate medications were also associated with lower EuroQol Five Dimensions
      Questionnaire scores [- 0.030 (0.010), p = 0.003] and Dementia Quality of Life
      Questionnaire-Self-Report-Utility scores [- 0.020 (0.009), p = 0.029]. Exposure
      to both Drug Burden Index-associated medications and potentially inappropriate
      medications was associated with lower Dementia Quality of Life Questionnaire-Self
      Report-Utility scores [- 0.034 (0.017), p = 0.049]. CONCLUSION: Exposure to
      anticholinergic and sedative medications and potentially inappropriate
      medications occurred in over three-quarters of a population of older adults in
      residential care and was associated with a lower quality of life.

PMID- 29322472
TI  - The prevalence and risk factors of hepatitis B flares in chronic hepatitis B
      patients receiving glucocorticoid pulse therapy.
AB  - Background The frequency and risks of hepatitis B reactivation in patients
      receiving glucocorticoid pulse therapy has not been reported. Objective The aim
      of our study was to investigate the possibility of glucocorticoid pulse therapy
      related hepatitis B flare. Setting A Taiwanese tertiary hospital. Methods Chronic
      hepatitis B patients underwent glucocorticoid pulse therapy were retrospectively
      collected. The prevalence of hepatitis B flare was counted, and the statistic
      analysis with logistic regression was adapted to assess the associated risk
      factors. Main outcome measure The prevalence and associated risk factors of the
      individuals with hepatitis B flare after glucocorticoid pulse therapy were
      collected and analyzed. Results A total of 112 patients were identified. Forty
      patients had received prophylactic antiviral therapy and none of them developed
      hepatitis B flare. Among the 72 patients who had not received antiviral
      prophylaxis, 11 of them (15.3%) experienced hepatitis B flares. Those individuals
      with hepatitis B flares, comparing to those without, were younger (37.4 +/- 13.3
      vs. 46.0 +/- 11.1, p = 0.038), had higher ratio of HBeAg positivity (50 vs.
      15.9%, p = 0.017), higher percentage of high hepatitis B viral load (81.8 vs.
      8.3%, p = 0.002), higher maintenance glucocorticoid dose (prednisone or
      equivalent 22.7 +/- 14.9 vs. 10.7 +/- 12.4 mg, p = 0.003) and higher ratio of
      cyclophosphamide use (27.3 vs. 1.6%, p = 0.010). After multivariate analysis,
      only higher dose of maintenance glucocorticoid was related to hepatitis B flare
      (odds ratio, 1.08; 95% CI, 1.01-1.16). Conclusion A higher maintenance
      glucocorticoid dosage is associated with the risk of hepatitis B flare after
      glucocorticoid pulse therapy. No hepatitis B flare occurred in patients receiving
      prophylactic antiviral therapy before glucocorticoid pulse therapy.

PMID- 29322474
TI  - Pharmacovigilance in developing countries (part II): a path forward.
AB  - In recent years, attention to pharmacovigilance has gained momentum in developing
      countries, however awareness of, and policies or systems for pharmacovigilance in
      most developing countries still lags sharply behind developed countries. This
      article proposes different strategies to encourage the introduction and sustain
      the advancement of robust pharmacovigilance systems in developing countries. To
      this end, this article seeks to accomplish the ultimate goal of pharmacovigilance
      in a developing country context; ensuring patient safety and promoting safe and
      rational use of drugs.

PMID- 29322473
TI  - Pharmaceutical care and health related quality of life outcomes over the past 25
      years: Have we measured dimensions that really matter?
AB  - Background Several measures of Health-Related Quality of Life (HRQoL) have been
      used to evaluate Pharmaceutical Care (PC) interventions in the past decades.
      However, their suitability for evaluation of PC services has not been
      comprehensively evaluated. Aim of the review The aim of this review was to
      perform content analysis of HRQoL measures used in PC studies to gain an insight
      into their suitability for evaluation of PC services. Method PC studies
      evaluating HRQoL as a primary or secondary outcomes were retrieved based on a
      literature search of articles published from 1990 to 2015, on Medline, Embase,
      International Pharmaceutical Abstracts, Global Health, PsycInfo, Web of Science,
      Cinahl, HealthStar, Cochrane Library, AUSThealth, Australian Medical Index, and
      Current content. Measures of HRQoL used in the studies were identified and
      relevant information was extracted. A conceptual model of a patient reported
      Medication-Related Burden Quality of Life was used to guide the analysis. Results
      117 studies were retrieved. Thirty-seven: 10 generic, 27 condition-specific HRQoL
      measures with a total of 1019 items about physical functioning (n = 430),
      psychological wellbeing (n = 288), social wellbeing (n = 119), physical burden (n
      = 69) and others (n = 113) were used in the studies. Only 34 of 1019 items were
      specifically related to medicines. Of these, the majority of items focused on
      other aspects of medicine such as adherence, rather than the burden imposed by
      medicine on quality of life. Conclusion A holistic analysis of HRQoL measures
      used in PC studies published over two and half decades provided a better insight
      into sensitivity and specificity of the measures to PC services. This review
      found that HRQoL measures used in PC studies provide a very limited coverage of
      themes related to the burden of medicine on quality of life. Therefore, may have
      limited potential for use as a sole humanistic measure when evaluating PC
      interventions. There is a scope for future research in the development of an
      alternative measure suitable for evaluation of the burden of medicine and the
      impact of PC interventions on quality of life outcomes.

PMID- 29322476
TI  - Negative regulators of cell death pathways in cancer: perspective on biomarkers
      and targeted therapies.
AB  - Cancer is a primary cause of human fatality and conventional cancer therapies,
      e.g., chemotherapy, are often associated with adverse side-effects, tumor drug
      resistance, and recurrence. Molecularly targeted therapy, composed of small
      molecule inhibitors and immunotherapy (e.g., monoclonal antibody and cancer
      vaccines), is a less harmful alternative being more effective against cancer
      cells whilst preserving healthy tissues. Drug-resistance, however, caused by
      negative regulation of cell death signaling pathways, is still a challenge.
      Circumvention of negative regulators of cell death pathways or development of
      predictive and response biomarkers is, therefore, quintessential. This review
      critically discusses the current state of knowledge on targeting negative
      regulators of cell death signaling pathways including apoptosis, ferroptosis,
      necroptosis, autophagy, and anoikis and evaluates the recent advances in clinical
      and preclinical research on biomarkers of negative regulators. It aims to provide
      a comprehensive platform for designing efficacious polytherapies including novel
      agents for restoring cell death signaling pathways or targeting alternative
      resistance pathways to improve the chances for antitumor responses. Overall, it
      is concluded that nonapoptotic cell death pathways are a potential research arena
      for drug discovery, development of novel biomarkers and targeted therapies.

PMID- 29322477
TI  - Aortic stenosis with right-sided aortic arch treated with transfemoral aortic
      valve implantation.

PMID- 29322475
TI  - The scope of drug-related problems in the home care setting.
AB  - Introduction While drug-related problems (DRPs) in the inpatient setting are well
      known, the scope of these problems in home care has not been critically
      evaluated. Aim of the Review Our primary objective was to evaluate the incidence
      and demographics of DRPs in home care. Our specific aims were to characterize the
      rate of potentially inappropriate medications (PIMs), medication errors (MEs) and
      adverse drug events (ADEs) and to identify risk factors which contribute to DRPs
      in the home care setting. Methods Pubmed, Embase and CiNAHL databases were
      systematically searched from January 2000 to December 2016 for all publications
      which quantitatively characterized DRPs in the home care setting. Results The
      most commonly reported DRPs characterized in studies were PIMs (n = 16), MEs (n =
      4) and the ME-subcategory medication-related discrepancies (n = 7). The frequency
      of PIMs ranged from 19.8 to 48.4%; up to 26% PIMs were considered severe.
      Polypharmacy (>= 9 drugs) and increasing age were the most common risk factors
      for DRPs. Insufficient interdisciplinary teamwork and inconsistent performance of
      medication reviews were also risks factors for DRPs. Patients and/or caregivers
      were responsible for 42.3% of DRPs. Discussion Compared with acute inpatient
      care, DRPs are more frequently reported in home care. The rate of DRPs varies
      depending upon the reference used to define the problem. Conclusion Transfer of
      complete medical records and the use of an interdisciplinary team have the
      potential to reduce DRPs, including MEs, specifically when integrating a
      pharmacist providing regular medication review. Importantly, patients and
      informal caregivers must be significant partners with this interdisciplinary
      team.

PMID- 29322478
TI  - Effect of health literacy on the quality of life of older patients with long-term
      conditions: a large cohort study in UK general practice.
AB  - PURPOSE: The levels of health literacy in patients with long-term conditions
      (LTCs) are critical for better disease management and quality of life (QoL).
      However, the impact of health literacy on QoL in older adults with LTCs is
      unclear. This study examined the association between health literacy and domains
      of QoL in older people with LTCs, investigating key socio-demographic and
      clinical variables, as confounders. METHODS: A prospective cohort study was
      conducted on older adults (n = 4278; aged 65 years and over) with at least one
      LTC, registered in general practices in Salford, UK. Participants completed
      measures of health literacy, QoL, multi-morbidity, depression, social support,
      and socio-demographic characteristics. Multivariate linear regressions were
      performed to examine the effects of health literacy on four QoL domains at
      baseline, and then changes in QoL over 12 months. RESULTS: At baseline, poor
      health literacy was associated with lower scores in all four QoL domains
      (physical, psychological, social relationships and environment), after adjusting
      for the effects of multi-morbidity, depression, social support and socio
      demographic factors. At 12-month follow-up, low health literacy significantly
      predicted declines in the physical, psychological and environment domains of QoL,
      but not in social relationships QoL. CONCLUSIONS: This is the largest, most
      complete assessment of the effects of health literacy on QoL in older adults with
      LTCs. Low health literacy is an independent indicator of poor QoL older patients
      with LTCs. Interventions to improve health literacy in older people with LTCs are
      encouraged by these findings.

PMID- 29322479
TI  - Do the Risk Factors Determine the Severity and Outcome of Cerebral Venous Sinus
      Thrombosis?
AB  - We report the burden of risk factors in cerebral venous sinus thrombosis (CVST)
      and its relationship with the clinical severity, extent of MRI and MRV
      abnormality, and outcome. One hundred and twenty-eight consecutive patients with
      CVST were included. Their demographic, presenting symptoms and neurological
      findings were noted and risk factors of CVST were evaluated. The outcomes were
      assessed using modified Rankin Scale (mRS). Based on the risk factors, the
      patients could be categorized as prothrombotic conditions only in 46 (35.9%),
      prothrombotic with other risk factors in 36 (28.1%), non-prothrombotic risk
      factors in 20 (15.6%), and no risk factors in 26 (20.3%). More than two risk
      factors were present in 33 (25.8%). Sixteen out of 22 (72.7%) patients with
      female gender-specific risk factors also had other prothrombotic conditions. On
      MRV, more than two sinuses were involved in 35 (27.3%) patients and 94 (73.4%)
      patients had parenchymal lesions on MRI. Thirty-one (24.2%) patients had poor
      outcome (mRS > 2) at discharge and 25/122 (20.5%) at 3 months. The number of risk
      factors was not related to clinical severity and extent of MRI or MRV
      abnormality. On multivariate analysis, age (OR 1.05, 95%CI 1.00-1.09, P = 0.03),
      GCS score (OR 5.30, 95%CI 1.25-22.24, P = 0.02), and mechanical ventilation (OR
      196.17, 95%CI 16.05, P = 0.001) predicted the outcome at 3 months.

PMID- 29322480
TI  - Intra-operative Video Characterization of Carotid Artery Pulsation Patterns in
      Case Series with Post-endarterectomy Hypertension and Hyperperfusion Syndrome.
AB  - Cerebral hyperperfusion syndrome (CHS) is a complication that can occur after
      carotid endarterectomy (CEA), the treatment of choice to decrease the subsequent
      risk of fatal or disabling stroke for patients with symptomatic severe stenosis
      of the carotid artery. Because of its rarity and complexity, the mechanism of the
      condition is still unclear, making its prevention via prediction and monitoring
      challenging. This is especially true during surgery, when multiple factors can
      induce physiological changes, including blood pressure and baroreceptor
      functions, which are crucial factors for post-CEA hypertension and CHS. Thus,
      with intra-operative videos taken by surgical microscopes, we employed a new
      video processing technique to magnify ordinarily invisible carotid artery
      pulsation patterns as rhythmic color fluctuations. We applied the technique for
      three CEA cases, two of which developed CHS with post-CEA hypertension. For those
      with CHS, abnormal pulsation patterns were detected at the site of the
      baroreceptors. The results suggested that intra-operative baroreceptor
      dysfunction can potentially be linked with post-operative hypertension, as well
      as the occurrence of CHS. Guided by the preliminary discovery, further
      investigation may help establish the introduced technique as a simple and
      contactless technique to help predict post-CEA hypertension and CHS in order to
      facilitate the management and understanding of the condition and improve the care
      of CEA.

PMID- 29322481
TI  - Influence of Thrombolysis on the Safety and Efficacy of Blocking Platelet
      Adhesion or Secretory Activity in Acute Ischemic Stroke in Mice.
AB  - In acute ischemic stroke (AIS), there is an alarming discrepancy between
      recanalization rates of up to 70% by combined recombinant tissue-type plasminogen
      activator (rt-PA) therapy and mechanical thrombectomy, and no clinical benefit in
      at least every second stroke patient. This is partly due to ischemia/reperfusion
      (I/R) injury. In a translational approach, we used mice lacking dense- (Unc13d-/
      ) or alpha-granules (Nbeal2-/-) and mice after blocking of platelet glycoprotein
      receptor (GP) Ib conferring protection from I/R injury. These mice underwent
      transient middle cerebral artery occlusion (tMCAO) and, as in the clinic, were
      treated with rt-PA. Our data show that rt-PA treatment is still safe in
      conjunction with selected anti-platelet therapies and pave the way for eagerly
      awaited additive treatment options in acute human stroke.

PMID- 29322482
TI  - Variation in cell size of the diatom Coscinodiscus granii influences
      photosynthetic performance and growth.
AB  - Cell size has implications for the package effect in photon absorption as well as
      for metabolic scaling of metabolism. In this study, we have avoided species
      related differences by using isolates of the marine planktonic diatom
      Coscinodiscus granii with cells of different sizes and grown at different light
      intensities to investigate their energy allocation strategies. To make full use
      of incident light, several fold variations in cellular chlorophyll a content were
      employed across cell size. This modulation of pigment-related light absorbance
      was deemed effective as similar light absorbing capacities were found in all
      treatments. Unexpected low values of O2 evolution rate at the highest irradiance
      level of 450 MUmol photons m-2 s-1 were found in medium and large cells,
      regardless of more photons being absorbed under these conditions, suggesting the
      operation of alternative electron flows acting as electron sinks. The growth rate
      was generally larger at higher irradiance levels except for the large cells, in
      which growth slowed at 450 MUmol photons m-2 s-1, suggesting that larger cells
      achieved a balance between growth and photoprotection by sacrificing growth rate
      when exposed to high light. Although the ratio of carbon demand to rates of
      uncatalysed CO2 diffusion to the cell surface reached around 20 in large cells
      grown under higher irradiance, the carbon fixation rate was not lowered, due to
      the presence of a highly effective carbon dioxide concentrating mechanism.

PMID- 29322483
TI  - Structural integrity of Synechocystis sp. PCC 6803 phycobilisomes evaluated by
      means of differential scanning calorimetry.
AB  - Phycobilisomes (PBSs) are supramolecular pigment-protein complexes that serve as
      light-harvesting antennae in cyanobacteria. They are built up by
      phycobiliproteins assembled into allophycocyanin core cylinders (ensuring the
      physical interaction with the photosystems) and phycocyanin rods (protruding from
      the cores and having light-harvesting function), the whole PBSs structure being
      maintained by linker proteins. PBSs play major role in light-harvesting
      optimization in cyanobacteria; therefore, the characterization of their
      structural integrity in intact cells is of great importance. The present study
      utilizes differential scanning calorimetry and spectroscopy techniques to explore
      for the first time, the thermodynamic stability of PBSs in intact Synechocystis
      sp. PCC 6803 cells and to probe its alteration as a result of mutations or under
      different growth conditions. As a first step, we characterize the thermodynamic
      behavior of intact and dismantled PBSs isolated from wild-type cells (having
      fully assembled PBSs) and from CK mutant cells (that lack phycocyanin rods and
      contain only allophycocyanin cores), and identified the thermal transitions of
      phycocyanin and allophycocyanin units in vitro. Next, we demonstrate that in
      intact cells PBSs exhibit sharp, high amplitude thermal transition at about 63 
      degrees C that strongly depends on the structural integrity of the PBSs
      supercomplex. Our findings implicate that calorimetry could offer a valuable
      approach for the assessment of the influence of variety of factors affecting the
      stability and structural organization of phycobilisomes in intact cyanobacterial
      cells.

PMID- 29322485
TI  - Effects of Ipragliflozin on Postprandial Glucose Metabolism and Gut Peptides in
      Type 2 Diabetes: A Pilot Study.
AB  - INTRODUCTION: Ipragliflozin is a novel antidiabetic drug that inhibits renal
      tubular sodium-glucose cotransporter-2 (SGLT2). The aim of this study was to
      evaluate the effects of ipragliflozin on glucose, insulin, glucagon, and
      gastrointestinal peptide responses to a meal tolerance test, as well as to
      investigate the glucose-lowering mechanisms of ipragliflozin. METHODS: Nine
      Japanese patients with obesity and type 2 diabetes mellitus were treated with
      ipragliflozin (50 mg/day) for 12 weeks. The postprandial profiles of glucose,
      insulin, glucagon, active glucagon-like peptide-1 (GLP-1), active glucose
      dependent insulinotropic polypeptide (GIP), ghrelin, and des-acyl ghrelin were
      measured before and 12 weeks after ipragliflozin treatment. RESULTS: Body weight,
      body fat mass, systolic blood pressure, and HbA1c and serum uric acid levels were
      significantly decreased after the treatment. Postprandial glucose and insulin
      levels were also significantly decreased. Postprandial glucagon increased both
      before and after ipragliflozin treatment; however, the increment tended to be
      smaller after treatment. Active GLP-1, active GIP, ghrelin, and des-acyl ghrelin
      did not change after treatment. CONCLUSION: Ipragliflozin improved glycemic
      control by reducing body weight, postprandial inappropriate glucagon secretion,
      and the postprandial insulin requirement. Although this was a short-term study
      with a small sample size, ipragliflozin may offer benefits for patients with
      obesity and type 2 diabetes mellitus. TRIAL REGISTRATION: University Hospital
      Medical Information Network (UMIN No. 000017195).

PMID- 29322487
TI  - Sydney Nano: small matters for big impact.

PMID- 29322486
TI  - Dapagliflozin and Empagliflozin Ameliorate Hepatic Dysfunction Among Chinese
      Subjects with Diabetes in Part Through Glycemic Improvement: A Single-Center,
      Retrospective, Observational Study.
AB  - INTRODUCTION: Sodium-glucose co-transporter 2 inhibitors (SGLT2i) improve hepatic
      dysfunction, although studies focusing on their underlying mechanisms are
      lacking, especially ones on dapagliflozin and empagliflozin. Here, we
      investigated the relationship between amelioration of hepatic dysfunction and
      improvement in various metabolic parameters among Chinese subjects with type 2
      diabetes (T2DM). METHODS: This was a single-center, retrospective, observational
      study that involved 115 Chinese participants with T2DM treated with either
      dapagliflozin or empagliflozin for at least 6 months between July 2016 and
      February 2017. RESULTS: Of the 115 participants included in this study, 69
      received dapagliflozin and 46 received empagliflozin. After 6 months of
      treatment, all patients showed significant improvements in body weight (BW),
      systolic blood pressure (SBP) and fasting glucose (FG) and glycated hemoglobin
      (HbA1c) levels. All participants also showed a significant reduction in serum
      alanine aminotransferase (ALT) levels, from 40.3 +/- 28.0 to 29.0 +/- 14.1 U/L (p
      < 0.001). Pearson's correlation analysis revealed a positive correlation between
      the reduction in ALT levels after treatment with the respective SGLT2i and
      changes in FG (p = 0.014) and HbA1c (p = 0.043) levels over 6 months, but not
      with changes in BW and SBP. Multiple linear regression analysis revealed that the
      reduction in serum ALT levels was independently associated with changes in both
      HbA1c and FG but not with the changes in the other clinical variables, including
      BW. CONCLUSIONS: Dapagliflozin and empagliflozin improved both metabolic and
      hepatic dysfunction as a class effect. The amelioration of hepatic dysfunction
      was mediated partly through an alleviation of hyperglycemia and possibly through
      an improvement in insulin resistance, independent of BW.

PMID- 29322484
TI  - Acute low-dose ketamine produces a rapid and robust increase in plasma BDNF
      without altering brain BDNF concentrations.
AB  - Peripheral BDNF changes after ketamine administration have been proposed as a
      biomarker for brain BDNF changes. However, published data are conflicting and
      come from studies in paired animal groups. This study determined the time course
      of plasma BDNF concentrations following the administration of a single 10 mg/kg
      dose of ketamine by different routes of administration in rats. Brain BDNF
      concentrations in prefrontal cortex, hippocampus and cortex were measured in the
      same animals. Ketamine administration resulted in a rapid and robust increase in
      plasma BDNF concentrations that were sustained for 240 min. In contrast, there
      were no changes in brain BDNF concentrations in prefrontal cortex, hippocampus or
      cortex and there were no correlations between peripheral and central BDNF
      concentrations. These data suggest that peripheral BDNF is unlikely to be a
      useful biomarker of acute central BDNF changes following ketamine.

PMID- 29322488
TI  - Difficulties with Fine Motor Skills and Cognitive Impairment in an Elderly
      Population: The Progetto Veneto Anziani.
AB  - OBJECTIVES: To investigate dysfunction in fine motor skills in a cohort of older
      Italian adults, identifying their prevalence and usefulness as indicators and
      predictors of cognitive impairment. DESIGN: Population-based longitudinal study
      with mean follow-up of 4.4 years. SETTING: Community. PARTICIPANTS: Older men and
      women enrolled in the Progetto Veneto Anziani (Pro.V.A.) (N = 2,361); 1,243
      subjects who were cognitively intact at baseline were selected for longitudinal
      analyses. MEASUREMENTS: Fine motor skills were assessed by measuring the time
      needed to successfully complete two functional tasks: putting on a shirt and a
      manual dexterity task. Cognitive impairment was defined as a Mini-Mental State
      Examination (MMSE) score less than 24. RESULTS: On simple correlation, baseline
      MMSE score was significantly associated with the manual dexterity task
      (correlation coefficient (r) = -0.25, P < .001) and time needed to put on a shirt
      (r = -0.29, P < .001). Over the study period, changes in time needed to perform
      the fine motor tasks were significantly associated with changes in MMSE (putting
      on a shirt: beta = 0.083, P = .003; manual dexterity task: beta = 0.098, P <
      .001). Logistic regression analyses confirmed that worse results on tasks were
      associated with cognitive impairment at baseline (odds ratio (OR) = 2.47, 95%
      confidence interval (CI) = 1.74-3.50, for the fourth quartile of time needed to
      put on a shirt; OR = 1.98, 95% CI = 1.42-2.76, for the fourth manual dexterity
      task quartile) and greater risk of cognitive impairment developing during follow
      up (OR = 4.38, 95% CI = 2.46-7.80, for the fourth quartile of time needed to put
      on a shirt; OR = 2.20, 95% CI = 1.30-3.72, for the fourth manual dexterity task
      quartile). CONCLUSIONS: Difficulties with fine motor skills are common in older
      adults, and assessing them may help to identify early signs of dementia, subjects
      at high risk to develop cognitive decline, and individuals who can be referred to
      specialists.

PMID- 29322489
TI  - Measurement in pediatric epilepsy self-management: A critical review.
AB  - : Given the paucity of information available regarding self-management, the aims
      of this paper are to synthesize the literature on factors associated with and
      measures to assess self-management in pediatric epilepsy. INCLUSION CRITERIA:
      youth birth to 18 years with a seizure disorder or an epilepsy diagnosis and/or
      their caregivers, published 1985-2014 in English, and conducted in countries with
      a very high human development index. The review was conducted in 6 phases: (1)
      identification of bibliographical search criteria and databases; (2) abstract
      assessment; (3) full article review; (4) organization of final citations into
      categories; (5) identification of predictors, potential mediators/moderators, and
      outcomes associated with self-management factors and categorization of factors as
      influences, processes, or behaviors across individual, family, community, and
      health care domains; and (6) critique of self-management instrument studies.
      Twenty-five studies that evaluated factors associated with self-management were
      identified. Individual and family-focused factors were the most commonly studied
      predictors of self-management, with psychosocial care needs and self-efficacy for
      seizure management identified as key factors associated with pediatric epilepsy
      self-management. Few studies have included mediator and moderator analyses.
      Measures of adherence were the most commonly used outcome. There has been a
      predominant focus on pediatric epilepsy influences and processes that are
      modifiable in nature, potentially at the expense of evidence for the role of
      community and health systems in pediatric epilepsy self-management. The 6 self
      management instrument tools reported scientific rationale and good psychometric
      properties. Results highlight several key modifiable cognitive and behavioral
      targets for skills development: adherence, self-efficacy for seizure management,
      attitudes toward epilepsy, and family variables. Moving forward, a comprehensive
      pediatric epilepsy self-management model, well-validated measures of self
      management behaviors, mediator/moderator designs to examine the complex
      relationships between predictors and pediatric epilepsy self-management outcomes,
      and studies examining the community and health care domains of self-management
      are necessary.

PMID- 29322490
TI  - The rs75932628 and rs2234253 polymorphisms of the TREM2 gene were associated with
      susceptibility to frontotemporal lobar degeneration in Caucasian populations.
AB  - Polymorphisms of the triggering receptor expressed on myeloid cells 2 (TREM2)
      gene have been reported to be potentially associated with the risks of developing
      frontotemporal lobar degeneration (FTLD), with inconsistent conclusions. This
      study aims to comprehensively investigate the potential role of TREM2 variants in
      FTLD risks via a meta-analysis. We included a total of eight eligible articles.
      For TREM2 rs75932628, we observed a significantly increased FTLD risk in the
      models of T vs. C [Association Test, odds ratio (OR) = 2.43, 95% confidence
      interval (CI) = 1.43~4.14, P = 0.001], CT vs. CC (OR = 2.27, 95% CI = 1.39~3.71,
      P = 0.001), CT + TT vs. CC (OR = 2.27, 95% CI = 1.38~3.71, P = 0.001), and
      Carrier T vs. C (OR = 2.26, 95% CI = 1.38~3.69, P = 0.001). Similarly, we
      observed positive results for TREM2 rs2234253 in all of the genetic models (all
      OR > 1, P = 0.030). Nevertheless, we did not observe any statistical difference
      between the case and control groups in the pooled analyses of TREM2 rs142232675
      and rs143332484 (all P > 0.05). Our findings identified the rs75932628 and
      rs2234253 polymorphisms of the TREM2 gene as risk factors for FTLD in Caucasian
      populations.

PMID- 29322492
TI  - Have we reached the end for throat packs inserted by anaesthetists?

PMID- 29322493
TI  - The struggle for Via Bologna street market: crisis, racial denial and speaking
      back to power in Naples Italy.
AB  - This paper is based on ethnographic research conducted with migrant and Italian
      street vendors in Naples, southern Italy, in 2012. It tells the story of Via
      Bologna market which was nearly closed down by the City Hall at the time. Naples
      is a city where issues of poverty and unemployment pre-date and have been
      exacerbated by manifold narratives of crisis now unfolding across Europe
      regarding the economy, political legitimacy, security and migration. Street
      markets have always been an important and visible economic survival strategy for
      both Neapolitans and migrants there. This article shows how the Via Bologna
      street vendors appropriated and adapted discourses about crisis to form their own
      cosmopolitan social movement that halted the closure of the market. It argues
      that, in the age of globalized migration, the multilingual nature of such
      collective action is central to understanding social struggles that must be
      organized between marginalized groups of people divided by race, religion,
      politics and legal status. This, frequently ambiguous, transcultural solidarity
      speaks back against a mainstream post-racial discourse - often articulated by the
      Neapolitan street vendors at the market - that would reduce the complexity of
      such collective action to questions of poverty and class struggle.

PMID- 29322491
TI  - Influence of Prehospital Function and Strength on Outcomes of Critically Ill
      Older Adults.
AB  - OBJECTIVES: To understand the influence of prehospital physical function and
      strength on clinical outcomes of critically ill older adults. DESIGN: Secondary
      analysis of prospective cohort study. SETTING: Health, Aging and Body Composition
      (Health ABC) Study. PARTICIPANTS: Of 3,075 older adult Health ABC participants,
      we identified 575 (60% white, 61% male, mean age 79) with prehospital function or
      grip strength measurements within 2 years of an intensive care unit stay.
      MEASUREMENTS: The primary analysis evaluated the association between prehospital
      walk speed and mortality, and secondary analyses focused on associations between
      function or grip strength and mortality or hospital length of stay. Function and
      grip strength were analyzed as continuous and categorical predictors. RESULTS:
      Slower prehospital walk speed was associated with greater risk of 30-day
      mortality (for each 0.1 m/s slower, odds ratio = 1.13, 95% confidence interval
      (CI) = 1.04-1.23, P = .004). Grip strength, chair stands, and balance had weaker,
      non-statistically significant associations with 30-day mortality. Participants
      with slower prehospital walk speed (hazard ratio (HR) = 0.94, 95% CI = 0.90-0.98,
      P = .005) and weak grip strength (HR = 0.85, 95% CI = 0.73-0.99, P = .03) were
      less likely to be discharged from the hospital alive. All function and strength
      measures were significantly associated with 1-year mortality. CONCLUSION: Slow
      prehospital walk speed was strongly associated with greater 30-day mortality and
      longer hospital stay in critically ill older adults, and measures of function and
      strength were associated with 1-year mortality. These data add to the
      accumulating evidence on the relationship between physical function and critical
      care outcomes.

PMID- 29322494
TI  - Common Primary and Secondary Causes of Headache in the Elderly.
AB  - OBJECTIVE/BACKGROUND: Headache in the elderly, defined as individuals aged 65 and
      older, although less prevalent than younger individuals, can present as a
      diagnostic challenge, given the increase in potentially fatal diseases within
      this population. METHODS: These individuals require a complete history,
      neurological examination, and assessment of potential secondary causes of
      headaches. RESULTS: Secondary causes include temporal or giant cell arteritis,
      subdural hematomas, central nervous system (CNS) tumors, strokes, and CNS
      infections. Once secondary conditions are ruled out, then primary causes of
      headache are considered such as tension-type headache, migraine, cluster
      headache, or hypnic headache. CONCLUSION: This article reviews the distinguishing
      characteristics of the most common types of headache in patients over the age of
      65 years old, along with potential diagnostic tests and treatment.

PMID- 29322495
TI  - Doing better (or worse) than one's parents: Social status, mobility, and
      performance-avoidance goals.
AB  - BACKGROUND: Previous research has shown that, when succeeding in higher
      education, first-generation (FG) students endorse more performance-avoidance
      goals (i.e., the fear of performing poorly) than continuing-generation (CG)
      students. AIMS: In this study, individual mobility is examined as a predictor of
      performance-avoidance goal endorsement. It is argued that FG students endorse
      more these goals than CG students because in higher education, the former (but
      not the latter) experience upward mobility. In addition, CG can also be at risk
      of endorsing these goals when they are confronted with downward mobility.
      SAMPLE(S): Two studies were conducted with psychology students (N = 143 in Study
      1; N = 176 in Study 2). METHODS: In Study 1, FG and CG students' perceived upward
      mobility was measured. In Study 2, FG and CG students were provided with a
      feedback that suggested either upward or downward mobility. In both studies,
      participants reported their level of performance-avoidance goal endorsement.
      RESULTS: Results from Study 1 supported an indirect effect of status on
      performance-avoidance goals via a higher perception of upward mobility. Results
      from Study 2 supported that psychology students who face mobility (i.e., FG
      students who received better feedback than their usual level of performance, CG
      students who received worse feedback than their usual level of performance)
      increased their performance-avoidance goals the most. CONCLUSIONS: Taken
      together, the results of these studies support that one's actual social position
      and, even more, the social position one is about to reach are reliable predictors
      of performance-avoidance goals.

PMID- 29322497
TI  - Genetics of patella hypoplasia/agenesis.
AB  - The patella is a sesamoid bone, crucial for knee stability. When absent or
      hypoplastic, recurrent knee subluxations, patellofemoral dysfunction and early
      gonarthrosis may occur. Patella hypoplasia/agenesis may be isolated or observed
      in syndromic conditions, either as the main clinical feature (Nail-patella
      syndrome, small patella syndrome), as a clue feature which can help diagnosis
      assessment, or as a background feature that may be disregarded. Even in the
      latter, the identification of patella anomalies is important for an appropriate
      patient management. We review the clinical characteristics of these rare
      diseases, provide guidance to facilitate the diagnosis and discuss how the genes
      involved could affect patella development.

PMID- 29322498
TI  - Response to 'Serological diagnostics in the detection of IgG autoantibodies
      against human collagen VII in epidermolysis bullosa acquisita: a multicentre
      analysis': reply from authors.

PMID- 29322496
TI  - WT1 peptide-based immunotherapy for advanced thymic epithelial malignancies.
AB  - Thymic epithelial tumors are rare malignancies, and no optimal therapeutic
      regimen has been defined for patients with advanced disease. Patients with
      advanced thymic epithelial tumors, which were resistant or intolerable to prior
      therapies, were eligible for this study. Patients received 9 mer-WT1-derived
      peptide emulsified with Montanide ISA51 adjuvant via intradermal administration
      once a week as a monotherapy. After the 3-month-protocol treatment, the treatment
      was continued mostly at intervals of 2-4 weeks until disease progression or
      intolerable adverse events occurred. Of the 15 patients enrolled, 11 had thymic
      carcinoma (TC) and 4 had invasive thymoma (IT). Median period from diagnosis to
      the start of treatment was 13.3 and 65.5 months for TC and IT, respectively. No
      patients achieved a complete or partial response. Of the 8 evaluable TC patients,
      6 (75.0%) had stable disease (SD) and 2 had progressive disease (PD). Of the 4
      evaluable IT patients, 3 (75.0%) had SD and 1 (25.0%) had PD. Median period of
      monotherapy treatment was 133 and 683 days in TC and IT patients, respectively.
      No severe adverse events occurred during the 3-month-protocol treatment. As
      adverse events in long responders, thymoma-related autoimmune complications, pure
      red cell aplasia and myasthenia gravis occurred in two IT patients. Cerebellar
      hemorrhage developed in a TC patient complicated with Von Willebrand disease.
      Induction of WT1-specific immune responses was observed in the majority of the
      patients. WT1 peptide vaccine immunotherapy may have antitumor potential against
      thymic malignancies.

PMID- 29322499
TI  - Effect of body weight and behavioural factors on caries severity in Mexican rural
      and urban adolescents.
AB  - OBJECTIVES: To investigate if, in Mexican adolescents, body weight and caries
      severity are associated, and if this association differs between rural and urban
      populations. METHODS: Adolescents from the rural area of Tepancan and the city of
      Veracruz were enrolled. Caries was recorded using the International Caries
      Detection and Assessment System and the body mass index (BMI) was calculated.
      Oral habits (toothbrushing, flossing, dental check-ups) and dietary patterns
      (sweets intake) were assessed. A dummy variable between BMI and living area
      (BMI/Area) was generated. Data were analysed using STATA and a multinomial
      logistic regression model was run, using caries severity as the dependent
      variable. RESULTS: Four-hundred and sixty-four subjects, 12-15 years of age,
      participated (rural = 240; urban = 224). The BMI and area of residence were
      significantly associated (chi2 = 12.59, P < 0.01). Area was also associated with
      caries severity (chi2 = 24.23, P < 0.01), with the highest number of caries in
      dentine recorded in participants from the rural area. The dummy variable BMI/Area
      was related to caries severity (chi2 = 27.47, P < 0.01): overweight adolescents
      with caries in dentine were most frequently found in the rural area. A higher
      prevalence of caries in enamel and a lower prevalence of caries in dentine (P <
      0.01) were recorded in adolescents from the urban area, where better oral habits,
      but higher sweets intake (P = 0.04), were encountered. According to the
      multinomial logistic regression model, BMI/Area was significantly associated with
      caries severity (P < 0.01). CONCLUSIONS: Overweight was not associated with
      caries severity in the overall population, but it became a statistically
      significant risk indicator in adolescents living in the rural area.

PMID- 29322500
TI  - Seizure onset predicts its type.
AB  - OBJECTIVE: Epilepsy is characterized by transient alterations in brain
      synchronization resulting in seizures with a wide spectrum of manifestations.
      Seizure severity and risks for patients depend on the evolution and spread of the
      hypersynchronous discharges. With standard visual inspection and pattern
      classification, this evolution could not be predicted early on. It is still
      unclear to what degree the seizure onset zone determines seizure severity. Such
      information would improve our understanding of ictal epileptic activity and the
      existing electroencephalogram (EEG)-based warning and intervention systems,
      providing specific reactions to upcoming seizure types. We investigate the
      possibility of predicting the future development of an epileptic seizure during
      the first seconds of recordings after their electrographic onset. METHODS: Based
      on intracranial EEG recordings of 493 ictal events from 26 patients with focal
      epilepsy, a set of 25 time and frequency domain features was computed using
      nonoverlapping 1-second time windows, from the first 3, 5, and 10 seconds of
      ictal EEG. Three random forest classifiers were trained to predict the future
      evolution of the seizure, distinguishing between subclinical events, focal onset
      aware and impaired awareness, and focal to bilateral tonic-clonic seizures.
      RESULTS: Results show that early seizure type prediction is possible based on a
      single EEG channel located in the seizure onset zone with correct prediction
      rates of 76.2 +/- 14.5% for distinguishing subclinical electrographic events from
      clinically manifest seizures, 75 +/- 16.8% for distinguishing focal onset
      seizures that are or are not bilateral tonic-clonic, and 71.4 +/- 17.2% for
      distinguishing between focal onset seizures with or without impaired awareness.
      All predictions are above the chance level (P < .01). SIGNIFICANCE: These
      findings provide the basis for developing systems for specific early warning of
      patients and health care providers, and for targeting EEG-based closed-loop
      intervention approaches to electrographic patterns with a high inherent risk to
      become clinically manifest.

PMID- 29322501
TI  - Response to "Antiretroviral Therapy With Efavirenz in HIV-Infected Pregnant
      Women: Understanding the Possible Mechanisms for Drug-Drug Interaction".

PMID- 29322502
TI  - Systematic review of benefits or harms of routine anaesthetist-inserted throat
      packs in adults: practice recommendations for inserting and counting throat
      packs: An evidence-based consensus statement by the Difficult Airway Society
      (DAS), the British Association of Oral and Maxillofacial Surgery (BAOMS) and the
      British Association of Otorhinolaryngology, Head and Neck Surgery (ENT-UK).
AB  - Throat packs are commonly inserted by anaesthetists after induction of
      anaesthesia for dental, maxillofacial, nasal or upper airway surgery. However,
      the evidence supporting this practice as routine is unclear, especially in the
      light of accidentally retained throat packs which constitute 'Never Events' as
      defined by NHS England. On behalf of three relevant national organisations, we
      therefore conducted a systematic review and literature search to assess the
      evidence base for benefit, and also the extent and severity of complications
      associated with throat pack use. Other than descriptions of how to insert throat
      packs in many standard texts, we could find no study that sought to assess the
      benefit of their insertion by anaesthetists. Instead, there were many reports of
      minor and major complications (the latter including serious postoperative airway
      obstruction and at least one death), and many descriptions of how to avoid
      complications. As a result of these findings, the three national organisations no
      longer recommend the routine insertion of throat packs by anaesthetists but
      advise caution and careful consideration. Two protocols for pack insertion are
      presented, should their use be judged necessary.

PMID- 29322503
TI  - Antiretroviral Therapy With Efavirenz in HIV-Infected Pregnant Women:
      Understanding the Possible Mechanisms for Drug-Drug Interaction.

PMID- 29322504
TI  - A randomised controlled trial comparing needle movements during combined spinal
      epidural anaesthesia with and without ultrasound assistance.
AB  - Ultrasound assistance for neuraxial techniques may improve technical performance;
      however, it is unclear which populations benefit most. Our study aimed to
      investigate the efficacy of neuraxial ultrasound in women having caesarean
      section with combined spinal-epidural anaesthesia, and to identify factors
      associated with improved technical performance. Two-hundred and eighteen women
      were randomly allocated to ultrasound-assisted or control groups. All the women
      had a pre-procedure ultrasound, but only women in the ultrasound group had this
      information conveyed to the anaesthetist. Primary outcomes were first-pass
      success (a single needle insertion with no redirections) and procedure
      difficulty. Secondary outcomes were block quality, patient experience and
      complications. Exploratory sub-group analysis and regression analysis were used
      to identify factors associated with success. Data from 215 women were analysed.
      First-pass success was achieved in 67 (63.8%) and 42 (38.2%) women in the
      ultrasound and control groups, respectively (adjusted p = 0.001). Combined spinal
      epidural anaesthesia was 'difficult' in 19 (18.1%) and 33 (30.0%) women in the
      ultrasound and control groups, respectively (adjusted p = 0.09). Secondary
      outcomes did not differ significantly. Anaesthetists misidentified the
      intervertebral level by two or more spaces in 23 (10.7%) women. Sub-group
      analysis demonstrated a benefit for ultrasound in women with easily palpable
      spinous processes (adjusted p = 0.027). Regression analysis identified use of
      ultrasound and easily palpable spinous processes to be associated with first-pass
      success.

PMID- 29322506
TI  - Relationship between alpha-melanocyte stimulating hormone levels and therapeutic
      outcome of melanocyte transplantation and phototherapy in non-segmental patients
      with vitiligo: A prospective study.

PMID- 29322505
TI  - Impact of bistrand abasic sites and proximate orientation on DNA global structure
      and duplex energetics.
AB  - Bistrand lesions embedded within a single helical turn of tridecameric
      deoxyoligonucleotide duplexes represent a model system for exploring the impact
      of clustered lesions that occur in vivo and pose a significant challenge to
      cellular repair machineries. Such investigations are essential for understanding
      the forces that dictate lesion-induced mutagenesis, carcinogenesis, and
      cytotoxicity within a context that mimics local helical perturbations caused by
      an ionizing radiation event. This study characterizes the structural and energy
      profiles of DNA duplexes harboring synthetic abasic sites (tetrahydrofuran, F) as
      models of clustered bistrand abasic (AP) lesions. The standard tridecameric
      dGCGTACCCATGCG.dCGCATGGGTACGC duplex is employed to investigate the energetic
      impact of single and bistrand AP sites by strategically replacing one or two
      bases within the central CCC/GGG triplet. Our combined analysis of temperature
      dependent UV and circular dichroism (CD) profiles reveals that the proximity and
      relative orientation of AP sites within bistrand-damaged duplexes imparts a
      significant thermodynamic impact. Specifically, 3'-staggered lesions (CCF/GFG)
      exert a greater destabilizing effect when compared with their 5'-counterpart
      (FCC/GFG). Moreover, a duplex harboring the central bistrand AP lesion (CFC/GFG)
      is moderately destabilized yet exhibits distinct properties relative to both the
      3' and 5'-orientations. Collectively, our energetic data are consistent with
      structural studies on bistrand AP-duplexes of similar sequence in which a 3'
      staggered lesion exerts the greatest perturbation, a finding that provides
      significant insight regarding the impact of orientation on lesion repair
      processing efficiency.

PMID- 29322507
TI  - Adherence to Mediterranean Diet Reduces Incident Frailty Risk: Systematic Review
      and Meta-Analysis.
AB  - OBJECTIVES: To conduct a systematic review of the literature on prospective
      cohort studies examining associations between adherence to a Mediterranean diet
      and incident frailty and to perform a meta-analysis to synthesize the pooled risk
      estimates. DESIGN: Systematic review and meta-analysis. SETTING: Embase, MEDLINE,
      CINAHL, PsycINFO, and Cochrane Library were systematically searched on September
      14, 2017. We reviewed references of included studies and relevant review papers
      and performed forward citation tracking for additional studies. Corresponding
      authors were contacted for additional data necessary for a meta-analysis.
      PARTICIPANTS: Community-dwelling older adults (mean age >=60). MEASUREMENTS:
      Incident frailty risk according to adherence to a Mediterranean diet. RESULTS:
      Two reviewers independently screened the title, abstract, and full text to
      ascertain the eligibility of 125 studies that the systematic search of the
      literature identified, and four studies were included (5,789 older people with
      mean follow-up of 3.9 years). Two reviewers extracted data from the studies
      independently. All four studies provided adjusted odds ratios (ORs) of incident
      frailty risk according to three Mediterranean diet score (MDS) groups (0-3, 4-5,
      and 6-9). Greater adherence to a Mediterranean diet was associated with
      significantly lower incident frailty risk (pooled OR = 0.62, 95% CI = 0.47-0.82,
      P = .001 for MDS 4-5; pooled OR = 0.44, 95% CI = 0.31-0.64, P < .001 for MDS 6-9)
      than poorer adherence (MDS 0-3). Neither significant heterogeneity (I2  = 0-16%,
      P = .30) nor evidence of publication bias was observed. CONCLUSION: Greater
      adherence to a Mediterranean diet is associated with significantly lower risk of
      incident frailty in community-dwelling older people. Future studies should
      confirm these findings and evaluate whether adherence to a Mediterranean diet can
      reduce the risk of frailty, including in non-Mediterranean populations.

PMID- 29322508
TI  - A novel homozygous variant in BMPR1B underlies acromesomelic dysplasia Hunter
      Thompson type.
AB  - Acromesomelic dysplasia is genetically heterogeneous group of skeletal disorders
      characterized by short stature and acromelia and mesomelia of limbs.
      Acromesomelic dysplasia segregates in an autosomal recessive pattern and is
      caused by biallelic sequence variants in three genes (NPR2, GDF5, and BMPR1B). A
      consanguineous family of Pakistani origin segregating a subtype of acromesomelic
      dysplasia called Hunter-Thompson was clinically and genetically evaluated.
      Genotyping of microsatellite markers and linkage analysis revealed a 7.78 Mb
      homozygous region on chromosome 4q22.3, which harbors BMPR1B. Sequence analysis
      of the gene revealed a novel homozygous missense variant (c.1190T > G,
      p.Met397Arg) that segregates with the disease phenotype within the family and
      produced a Logarithm of odds (LOD) score of 3.9 with the disease phenotype. This
      study reports on the first familial case of acromesomelic dysplasia Hunter
      Thompson type. It is also the first report of BMPR1B underlying the etiology of
      acromesomelic dysplasia Hunter-Thompson type.

PMID- 29322509
TI  - Identity fusion predicts endorsement of pro-group behaviours targeting
      nationality, religion, or football in Brazilian samples.
AB  - A visceral feeling of oneness with a group - identity fusion - has proven to be a
      stronger predictor of pro-group behaviours than other measures of group bonding,
      such as group identification. However, the relationship between identity fusion,
      other group alignment measures and their different roles in predicting pro-group
      behaviour is still controversial. Here, we test whether identity fusion is
      related to, but different from, unidimensional and multidimensional measures of
      group identification. We also show that identity fusion explains further variance
      of the endorsement of pro-group behaviour than these alternative measures and
      examine the structural and discriminant properties of identity fusion and group
      identification measures in three different contexts: nationality, religion, and
      football fandom. Finally, we extend the fusion literature to a new culture:
      Brazil. To the best of our knowledge, this is the first research explicitly
      addressing a comparison between these two forms of group alignment, identity
      fusion and identification with a group, and their role in predicting pro-group
      behaviours.

PMID- 29322511
TI  - Discrimination, religious and cultural factors, and Middle Eastern/Arab
      Americans' psychological distress.
AB  - OBJECTIVE(S): We investigated (1) the moderating role of religiosity in the link
      between religious affiliation and ethnic discrimination and (2) the moderating
      roles of religiosity, ethnic identity, and family connectedness in the relations
      between ethnic discrimination and psychological distress. METHOD: Our sample
      consisted of 122 (60% women, 40% men) Middle Eastern/Arab Americans (MEAAs),
      ranging in age from 18 to 82 years old, who completed an online survey. RESULTS:
      Muslim identification predicted discrimination for MEAAs with high but not low
      religiosity. Higher levels of discrimination, more family connectedness, the
      interaction of discrimination and religiosity, and the interaction of
      discrimination and family connectedness were unique predictors of psychological
      distress. CONCLUSIONS: Religiosity is a risk factor for experiencing ethnic
      discrimination among Muslim identified MEAAs. MEAAs who have high religiosity and
      low to moderate levels of family connectedness are vulnerable to psychological
      distress associated with ethnic discrimination.

PMID- 29322510
TI  - Lolium perenne peptide immunotherapy is well tolerated and elicits a protective B
      cell response in seasonal allergic rhinitis patients.
AB  - BACKGROUND: Systemic allergic reactions are a risk for allergen immunotherapy
      that utilizes intact allergen preparations. We evaluated the safety, efficacy and
      immune mechanisms of short-course treatment with adjuvant-free Lolium perenne
      peptides (LPP) following a 6-week dose-escalation protocol. METHODS: In a
      prospective, dose-escalation study, 61 grass pollen-allergic patients received 2
      subcutaneous injections of LPP once weekly for 6 weeks. Safety was assessed
      evaluating local reactions, systemic reactions and adverse events. The clinical
      effect of LPP was determined by reactivity to the conjunctival provocation test
      (CPT). Specific IgE, IgG4 and blocking antibodies were measured at baseline (V1),
      during (V6) and after treatment (V8). RESULTS: No fatality, serious adverse event
      or epinephrine use was reported. Mean wheal diameters after injections were <0.6
      cm and mean redness diameters <2.5 cm, independent of dose. Transient and mostly
      mild adverse events were reported in 33 patients. Two patients experienced a
      grade I and 4 patients a grade II reaction (AWMF classification). At V8, 69.8% of
      patients became nonreactive to CPT. sIgG4 levels were higher at V6 (8.1-fold, P <
      .001) and V8 (12.2-fold, P < .001) than at V1. The sIgE:sIgG4 ratio decreased at
      V6 (-54.6%, P < .001) and V8 (-71.6%, P < .001) compared to V1. The absolute
      decrease in IgE-facilitated allergen binding was 18% (P < .001) at V6 and 25% (P
      < .001) at V8. CONCLUSION: Increasing doses of subcutaneous LPP appeared safe,
      substantially diminished reactivity to CPT and induced blocking antibodies as
      early as 4 weeks after treatment initiation. The benefit/risk balance of LPP
      immunotherapy remains to be further evaluated in large studies.

PMID- 29322512
TI  - Serum inflammatory markers in relation to prostate cancer severity and death in
      the Swedish AMORIS study.
AB  - Inflammation is a well-documented driver of cancer development and progression.
      However, little is known about its role in prostate carcinogenesis. Thus, we
      examined the association of C-reactive protein (CRP), haptoglobin, albumin and
      white blood cells (WBC) with prostate cancer (PCa) severity (defined by PCa risk
      category and clinicopathological characteristics) and progression (defined by PCa
      death). We selected 8,471 Swedish men with newly diagnosed PCa who had exposure
      measurements taken approximately 14 years prior to diagnosis. We calculated odds
      ratio (OR) and 95% confidence interval (CI) for the associations between the
      inflammatory markers and PCa severity using logistic regression, while Cox
      proportional hazard regression was used for the associations with overall and PCa
      death. Serum CRP levels were associated with increased odds of high risk and
      metastatic PCa, and high PSA levels (>=20 ug/L) (OR: 1.29; 95% CI: 1.06-1.56,
      1.32; 1.05-1.65 and 1.51; 1.26-1.81, respectively). Similarly, higher haptoglobin
      levels were associated with increased odds of metastatic PCa, high PSA level and
      possibly high grade PCa (1.38; 1.10-1.74, 1.50; 1.17-1.93 and 1.25; 1.00-1.56,
      respectively). Albumin was positively associated with Gleason 4 + 3 tumour (1.38;
      1.02-1.86) and overall death (HRunit increase in log : 1.60; 95% CI: 1.11-2.30),
      but inversely associated with high risk PCa and high PSA levels (>=20 ug/L)
      (0.71; 0.56-0.89 and 0.72; 0.5 9-0.90). WBC was associated with increased odds of
      T3-T4 PCa. Except for albumin, none of these markers were associated with PCa
      death or overall death. Systemic inflammation as early as 14 years prior to
      diagnosis may influence prostate cancer severity.

PMID- 29322513
TI  - Periodontitis and cancer mortality: Register-based cohort study of 68,273 adults
      in 10-year follow-up.
AB  - Periodontitis, a multifactorial infection-induced low-grade chronic inflammation,
      can influence the process of carcinogenesis. We studied with 10 years follow-up
      of 68,273 adults-based cohort the involvement of periodontitis as a risk factor
      for cancer mortality. Periodontal status was defined based on procedure codes of
      periodontal treatment. Rate ratios and absolute differences of overall and cancer
      mortality rates were assessed with respect to periodontal status using
      multiplicative and additive Poisson regression models, respectively. We adjusted
      for effect of age, sex, calendar time, socio-economic status, oral health, dental
      treatments and diabetes. Data about smoking or alcohol consumption were not
      available. Altogether 797 cancer deaths occurred during 664,020 person-years
      accumulated over a mean 10.1-year follow-up. Crude cancer mortality rate per
      10,000 person-years for participants without and with periodontitis was 11.36
      (95% CI 10.47-12.31) and 14.45 (95% CI 12.51-16.61), respectively. Crude rate
      ratios for periodontitis indicated an increased risk of overall (RR 1.27, 95% CI
      1.08-1.39) and pancreatic cancer (RR 1.69, 95% CI 1.04-2.76) mortality. After
      adjustment, the results showed even stronger associations of periodontitis with
      increased overall (RR 1.33, 95% CI 1.10-1.58) and pancreatic cancer (RR 2.32, 95%
      CI 1.31-3.98) mortality. A higher pancreatic cancer mortality among individuals
      with periodontitis contributed considerably to the difference in overall cancer
      mortality, but this difference was not due to pancreatic cancer deaths alone.

PMID- 29322514
TI  - The Yin and Yang of YY1 in tumor growth and suppression.
AB  - Yin Yang-1 (YY1) is a zinc finger protein and member of the GLI-Kruppel family
      that can activate or inactivate gene expression depending on interacting
      partners, promoter context and chromatin structure, and may be involved in the
      transcriptional control of ~10% of the total mammalian gene set. A growing body
      of literature indicates that YY1 is overexpressed in multiple cancer types and
      that increased YY1 levels correlate with poor clinical outcomes in many cancers.
      However, the role of YY1 in the promotion or suppression of tumor growth remains
      controversial and its regulatory effects may be tumor cell type dependent at
      least in experimental systems. The molecular mechanisms responsible for the
      apparently conflicting roles of YY1 are not yet fully elucidated. This review
      highlights recent advances in our understanding of regulatory insights involving
      YY1 function in a range of cancer types. For example, YY1's roles in tumor growth
      involve stabilization of hypoxia-inducible factor HIF-1alpha in a p53 independent
      manner, negative regulation of miR-9 transcription, control of MYCT1
      transcription, a novel miR-193a-5p-YY1-APC axis, intracellular ROS and
      mitochondrial superoxide generation, p53 reduction and EGFR activation, control
      of genes associated with mitochondrial energy metabolism and miRNA regulatory
      networks involving miR-7, miR-9, miR-34a, miR-186, miR-381, miR-584-3p and miR
      635. On the other hand, tumor suppressor roles of YY1 appear to involve YY1
      stimulation of tumor suppressor BRCA1, increased Bax transcription and apoptosis
      involving cytochrome c release and caspase-3/-7 cleavage, induction of heme
      oxygenase-1, inhibition of pRb phosphorylation and p21 binding to cyclin D1 and
      cdk4, reduced expression of long noncoding RNA of SOX2 overlapping transcript,
      and MUC4/ErbB2/p38/MEF2C-dependent downregulation of MMP-10. YY1 expression is
      associated with that of cancer stem cell markers SOX2, BMI1 and OCT4 across many
      cancers suggesting multidynamic regulatory control and groups of cancers with
      distinct molecular signatures. Greater understanding of the mechanistic roles of
      YY1 will in turn lead to the development of more specific approaches to modulate
      YY1 expression and activity with therapeutic potential.

PMID- 29322515
TI  - Current practices in perioperative blood management for patients undergoing liver
      resection: a survey of surgeons and anesthesiologists.
AB  - BACKGROUND: Development of intraoperative techniques and blood management
      strategies in liver resection, and the multidisciplinary nature of perioperative
      transfusion decision making, creates an opportunity for practice variation. The
      aim of this study was to describe the current practices in perioperative blood
      management and explore differences between surgeons and anesthesiologists. STUDY
      DESIGN AND METHODS: A Web-based survey was developed, piloted, and circulated to
      Canadian liver surgeons and anesthesiologists. The survey focused on management
      of preoperative anemia, blood conservation strategies, estimation of blood loss,
      and transfusion decision making in a multidisciplinary setting. RESULTS: A total
      of 198 physicians received the survey, with 117 responding (59%). Most responding
      surgeons (67%) perform more than 20 liver resections per year, while most
      responding anesthesiologists (90%) take part in fewer than 20. Anesthesiologists
      most commonly stated that preoperative anemia is managed by someone else (38%),
      while surgeons most commonly reported "no specific treatment" (45%). The most
      common intraoperative blood conservation technique used is administration of
      antifibrinolytics (63% used them at least occasionally). The most important
      factor for anesthesiologists when deciding on an intraoperative transfusion was
      hemoglobin value (47%); for surgeons, it was patient hemodynamics (33%). Compared
      to when they started their career, 60% of respondents felt that they were less
      likely to transfuse a patient now. CONCLUSION: The results of our survey provide
      insights into current transfusion practice and decision making in liver
      resection, including a comparison between anesthesiologist and surgeon
      transfusion behavior. Management of preoperative anemia, increased use of
      intraoperative blood conservation techniques, and improved communication between
      providers were identified as targets for quality improvement.

PMID- 29322516
TI  - A fully analytical integration of properties over the 3D volume of the beta
      sphere in topological atoms.
AB  - Atomic multipole moments associated with a spherical volume fully residing within
      a topological atom (i.e., the beta sphere) can be obtained analytically. Such an
      integration is thus free of quadrature grids. A general formula for an arbitrary
      rank spherical harmonic multipole moment is derived, for an electron density
      comprising Gaussian primitives of arbitrary angular momentum. The closed
      expressions derived here are also sufficient to calculate the electrostatic
      potential, the two types of kinetic energy, as well as the potential energy
      between atoms. Some integrals have not been solved explicitly before but through
      recursion and substitution are broken down to more elementary listed integrals.
      The proposed method is based on a central formula that shifts Gaussian primitives
      from one center to another, which can be derived from the well-known plane-wave
      expansion (or Rayleigh equation). (c) 2018 The Authors. Journal of Computational
      Chemistry Published by Wiley Periodicals, Inc.

PMID- 29322517
TI  - Discordant human T-lymphotropic virus screening with Western blot confirmation:
      evaluation of the dual-test algorithm for US blood donations.
AB  - BACKGROUND: Human T-lymphotropic virus (HTLV) blood donation screening has used a
      dual-testing algorithm beginning with either a chemiluminescent immunoassay or
      enzyme-linked immunosorbent screening assay (ELISA). Before the availability of a
      licensed HTLV supplemental assay, repeat-reactive (RR) samples on a first assay
      (Assay 1) were retested with a second screening assay (Assay 2). Donors with RR
      results by Assay 2 were deferred from blood donation and further tested using an
      unlicensed supplemental test to confirm reactivity while nonreactive (NR) donors
      remained eligible for donation until RR on a subsequent donation. This "dual
      test" algorithm was replaced in May 2016 with the requirement that all RRs by
      Assay 1 be further tested by a licensed HTLV supplemental test (Western blot
      [WB]). In this study, we have requalified the dual-test algorithm using the
      available licensed HTLV WB. STUDY DESIGN AND METHODS: We tested 100 randomly
      selected HTLV RRs on screening Assay 1 (Abbott PRISM chemiluminescent
      immunoassay) but NR on screening Assay 2 (Avioq ELISA) by a Food and Drug
      Administration-licensed WB (MP Biomedicals) to ensure that no confirmed positives
      were among those that were RR by Assay 1 but NR by Assay 2. RESULTS: Of the 100
      samples evaluated, 79 of 100 were WB seronegative, 21 of 100 indeterminate, and 0
      of 100 seropositive. Of the 79 of 100 seronegative specimens, 73 of 79 did not
      express any bands on WB. CONCLUSIONS: We demonstrated that none of the 100
      samples RR on Assay 1 but NR on Assay 2 were confirmed positive. This algorithm
      prevents such donors from requiring further testing and from being deferred.

PMID- 29322518
TI  - Pediatric heart transplantation-What are the risk factors for pacemaker
      implantation and how much pacing is required?
AB  - BACKGROUND: In an attempt to improve pacemaker therapy after pediatric
      transplantation, we investigated risk factors, indication for pacing, and pacing
      burden after pediatric heart transplantation. METHODS AND RESULTS: In this
      retrospective study, 139 pediatric heart transplant recipients, of whom 122 did
      not and 17 did require pacemakers, were investigated. Eleven of the 17 patients
      requiring a permanent pacemaker (PPM) received their heart from a female donor
      (68.8%); this compares to 48 of 122 patients (43.2%, P  =  0.082) in the group
      not requiring a pacemaker (No PPM). The donor age and height were significantly
      greater in the PPM group at a median of 25.26 years (16.29-48.00) and 160 cm (153
      170) compared with 11.96 years (1.73-19.95) and 141 cm (89-165) in the No PPM
      group (P  =  0.003 and 0.015, respectively). Of the 17 patients requiring
      pacemakers, 13 presented with sinus node dysfunction (SND) and four with
      atrioventricular block. The atrial pacing burden in patients with SND remained
      above 60% within the 5 years of follow-up investigated. There was no significant
      difference in mortality between those patients requiring a PPM and those not (Log
      Rank test: P  =  0.672). CONCLUSION: We found that in our cohort donor
      characteristics were key risk factors for pacemaker implantation in transplanted
      children. The data suggest that when patients require a pacemaker in
      posttransplant SND, they will require a relevant amount of pacing for at least 5
      years. The pacing burden after this point remains to be investigated. Mortality
      does not differ between pediatric heart transplant patients with and without
      pacemakers.

PMID- 29322520
TI  - Muscle cooling: too much of a good thing?

PMID- 29322519
TI  - Inactivation of chikungunya virus in blood components treated with
      amotosalen/ultraviolet A light or amustaline/glutathione.
AB  - BACKGROUND: Chikungunya virus, a mosquito-borne arbovirus, often co-circulates
      with the Zika, dengue, and yellow fever viruses in Aedes mosquito-infested areas
      where cases of arbovirus transfusion-transmitted infections have been reported.
      Building on past experience to help maintain the availability of safe components
      during major outbreaks of chikungunya virus in La Reunion, Italy, and Thailand
      and of Zika virus in the Pacific, the Caribbean, and the Americas, pathogen
      inactivation is a mitigation strategy to reduce the risk of transfusion
      transmitted infection. Inactivation of chikungunya virus was investigated for
      platelets in 100% plasma using amotosalen/ultraviolet A light, and in red blood
      cells using amustaline/glutathione. STUDY DESIGN AND METHODS: Platelets in 100%
      plasma and red blood cells (RBCs) were spiked with chikungunya virus. Infectious
      chikungunya virus titers were measured in contaminated blood products before and
      after treatment with amotosalen/ultraviolet A light for platelets in 100% plasma
      and after treatment with amustaline/glutathione for RBCs. Viral infectivity was
      quantified by plaque assay. RESULTS: The mean chikungunya virus infectivity
      titers before inactivation were 6.50 log10 plaque-forming units/mL for platelets
      in 100% plasma and 7.60 log10 plaque-forming units/mL for RBCs. No infectivity
      was detected after amotosalen/ultraviolet A light or amustaline/glutathione
      treatment, corresponding to greater than 6.5 log10 plaque-forming units/mL and
      greater than 7.1 log10 plaque-forming units/mL of inactivation, respectively.
      CONCLUSION: Robust levels of chikungunya virus inactivation were achieved for
      platelets in 100% plasma and for RBC components. The licensed
      amotosalen/ultraviolet A light technology and the amustaline/glutathione pathogen
      reduction system under development may provide an opportunity for comprehensive
      mitigation of the risk of chikungunya virus transfusion-transmitted infection by
      plasma, platelets, and RBCs.

PMID- 29322521
TI  - Fitting unanchored puzzle pieces in the skeleton: appropriate 3D scapular
      positions for the quadrupedal support in tetrapods.
AB  - Deducing the scapular positions of extinct tetrapod skeletons remains difficult,
      because the scapulae and rib cage are connected with each other not directly by
      skeletal joint, but by thoracic muscles. In extant non-testudine quadrupedal
      tetrapods, the top positions of the scapulae/suprascapulae occur at the anterior
      portion of the rib cage, above the vertebral column and near the median plane.
      The adequacy of this position was tested using three-dimensional mechanical
      models of Felis, Rattus and Chamaeleo that assumed stances on a forelimb on a
      single side and the hindlimbs. The net moment about the acetabulum generated by
      the gravity force and the contractive forces of the anti-gravity thoracic
      muscles, and the resistance of the rib to vertical compression between the
      downward gravity and upward lifting force from the anti-gravity thoracic muscle
      depend on the scapular position. The scapular position common among quadrupeds
      corresponds to the place at which the roll and yaw moments of the uplifted
      portion of the body are negligible, where the pitch moment is large enough to
      lift the body, and above the ribs having high strength against vertical
      compression. These relationships between scapular position and rib cage
      morphology should allow reliable reconstruction of limb postures of extinct taxa.

PMID- 29322522
TI  - Eye-specific segregation and differential fasciculation of developing retinal
      ganglion cell axons in the mouse visual pathway.
AB  - Prior to forming and refining synaptic connections, axons of projection neurons
      navigate long distances to their targets. While much is known about guidance cues
      for axon navigation through intermediate choice points, whether and how axons are
      organized within tracts is less clear. Here we analyze the organization of
      retinal ganglion cell (RGC) axons in the developing mouse retinogeniculate
      pathway. RGC axons are organized by both eye-specificity and topography in the
      optic nerve and tract: ipsilateral RGC axons are segregated from contralateral
      axons and are offset laterally in the tract relative to contralateral axon
      topographic position. To identify potential cell-autonomous factors contributing
      to the segregation of ipsilateral and contralateral RGC axons in the visual
      pathway, we assessed their fasciculation behavior in a retinal explant assay.
      Ipsilateral RGC neurites self-fasciculate more than contralateral neurites in
      vitro and maintain this difference in the presence of extrinsic chiasm cues. To
      further probe the role of axon self-association in circuit formation in vivo, we
      examined RGC axon organization and fasciculation in an EphB1-/- mutant, in which
      a subset of ipsilateral RGC axons aberrantly crosses the midline but targets the
      ipsilateral zone in the dorsal lateral geniculate nucleus on the opposite side.
      Aberrantly crossing axons retain their association with ipsilateral axons in the
      contralateral tract, indicating that cohort-specific axon affinity is maintained
      independently of guidance signals present at the midline. Our results provide a
      comprehensive assessment of RGC axon organization in the retinogeniculate pathway
      and suggest that axon self-association contributes to pre-target axon
      organization.

PMID- 29322524
TI  - A comprehensive analysis of neurotrophins and neurotrophin tyrosine kinase
      receptors expression during development of zebrafish.
AB  - Neurotrophins (NTF) are a family of secreted nerve growth factors with affinity
      for tyrosine kinase (Ntrk) and p75 receptors. To fully understand the variety of
      developmental roles played by NTFs, it is critical to know when and where genes
      encoding individual ligands and receptors are transcribed. Identification of ntf
      and ntrk transcripts in zebrafish development remains to be fully characterized
      for further uncovering the potential function(s) of the NTF signal transduction
      pathway. Here, we conducted a systematic analysis of the expression profiles of
      four ntf and five ntrk genes during zebrafish development using whole-mount in
      situ hybridization. Our study unveils new expression domains in the developing
      embryo, confirms those previously known, and shows that ntf and ntrk genes have
      different degrees of cell- and tissue-type specificity. The unique and
      overlapping expression patterns here depicted indicate the coordination of the
      redundant and divergent functions of NTFs and represent valuable tools for
      deciphering the molecular pathways involved in the specification and function of
      embryonic cell types.

PMID- 29322525
TI  - Zika virus RNA polymerase chain reaction on the utility channel of a commercial
      nucleic acid testing system.
AB  - BACKGROUND: Several countries have implemented safety strategies to reduce the
      risk of Zika virus (ZIKV) transmission through blood transfusion. These
      strategies have included nucleic acid amplification testing (NAT) of blood
      donations. In this study, a new real-time polymerase chain reaction (PCR) assay
      including internal control for the detection of ZIKV on the cobas omni Utility
      Channel (UC) on the cobas 6800 system is presented. STUDY DESIGN AND METHODS: PCR
      conditions and primer/probe concentrations were optimized on the LightCycler 480
      instrument. Optimized conditions were transferred to the cobas omni UC on the
      cobas 6800 system. Subsequently, the limit of detection (LOD) in plasma and
      urine, genotype inclusivity, specificity, cross-reactivity, and clinical
      sensitivity were determined. RESULTS: The 95% LOD of the ZIKV PCR assay on the
      cobas 6800 system was 23.0 IU/mL (95% confidence interval [CI], 16.5-37.5) in
      plasma and 24.5 IU/mL (95% CI, 13.4-92.9) in urine. The assay detected African
      and Asian lineages of ZIKV. The specificity was 100%. The clinical concordance
      between the newly developed ZIKV PCR assay and the investigational Roche cobas
      Zika NAT test was 83% (24/29). CONCLUSIONS: We developed a sensitive ZIKV PCR
      assay on the cobas omni UC on the cobas 6800 system. The assay can be used for
      large-scale screening of blood donations for ZIKV or for testing of blood donors
      returning from areas with ZIKV to avoid temporal deferral. This study also
      demonstrates that the cobas omni UC on the cobas 6800 system can be used for in
      house-developed PCR assays.

PMID- 29322523
TI  - Prevalence of pollen-induced allergic rhinitis with high pollen exposure in
      grasslands of northern China.
AB  - BACKGROUND: The aim of this study was to investigate the prevalence of
      epidemiologic and physician-diagnosed pollen-induced AR (PiAR) in the grasslands
      of northern China and to study the impact of the intensity and time of pollen
      exposure on PiAR prevalence. METHODS: A multistage, clustered and proportionately
      stratified random sampling with a field interviewer-administered survey study was
      performed together with skin prick tests (SPT) and measurements of the daily
      pollen count. RESULTS: A total of 6043 subjects completed the study, with a
      proportion of 32.4% epidemiologic AR and 18.5% PiAR. The prevalence was higher in
      males than females (19.6% vs 17.4%, P = .024), but no difference between the two
      major residential and ethnic groups (Han and Mongolian) was observed. Subjects
      from urban areas showed higher prevalence of PiAR than rural areas (23.1% vs
      14.0%, P < .001). Most PiAR patients were sensitized to two or more pollens
      (79.4%) with artemisia, chenopodium, and humulus scandens being the most common
      pollen types, which were similarly found as the top three sensitizing pollen
      allergens by SPT. There were significant regional differences in the prevalence
      of epidemiologic AR (from 18.6% to 52.9%) and PiAR (from 10.5% to 31.4%) among
      the six areas investigated. PiAR symptoms were positively associated with pollen
      counts, temperature, and precipitation (P < .05), but negatively with wind speed
      and pressure P < .05). CONCLUSION: Pollen-induced AR (PiAR) prevalence in the
      investigated region is extremely high due to high seasonal pollen exposure, which
      was influenced by local environmental and climate conditions.

PMID- 29322526
TI  - How are the charge transfer descriptors affected by the quality of the
      underpinning electronic density?
AB  - With the aim of investigating qualitatively and quantitatively the impact of
      using excited state relaxed or unrelaxed density for the estimation of nature and
      characteristic of electronic excited states, we analyzed the behavior of 52
      exchange correlation functionals for the prediction of density-based indexes such
      as those recently introduced in literature to evaluate the charge transfer
      distance (DCT ) (Le Bahers et al. J. Chem. Theory Comput. 2011, 7, 2498) in the
      case of a prototype family of push-pull dyes. Our results show that while a
      qualitatively consistent assessment of the nature of the excited states is
      obtained using either the unrelaxed or the relaxed density, from a quantitative
      standpoint we observe large discrepancies in the charge transfer distance for
      electronic transitions having substantial CT character. This behavior is
      independent of nature of the exchange-correlation functional used. (c) 2018 Wiley
      Periodicals, Inc.

PMID- 29322527
TI  - Thalamo-cortical projections to the macaque superior parietal lobule areas PEc
      and PE.
AB  - The exposed surface of the superior parietal lobule in macaque brain contains two
      architectonically defined areas named PEc and PE. The aim of the present study is
      the characterization of thalamic afferents of these two areas. For this purpose,
      retrograde neuronal tracers were injected, or placed in crystal form, in areas
      PEc and PE. We found that the two areas show a similar pattern of thalamic
      inputs, mainly originating from Lateral Posterior (LP), Pulvinar (Pul), Ventral
      Posterior Lateral (VPL), and Ventral Lateral (VL) nuclei, all structures known to
      be involved in visual, somatosensory, and/or sensorimotor processing. Minor
      afferents were observed from the Centromedian/Parafascicular complex (CM/PF),
      Central Lateral (CL), Ventral Anterior (VA), and Medial Dorsal (MD) nuclei. LP
      and VL were more strongly connected to PEc than to PE, while the other main
      thalamic inputs to the two areas showed slight differences in strength. The part
      of the Pul mostly connected with areas PEc and PE was the Medial Pul. No labeled
      cells were found in the retinotopically organized Lateral and Inferior Pul. In
      the somatotopically organized VPL and VL nuclei, labeled neurons were mainly
      found in regions likely to correspond to the trunk and limb representations (in
      particular the legs). These findings are in line with the sensory-motor nature of
      areas PEc and PE, and with their putative functional roles, being them suggested
      to be involved in the preparation and control of limb interaction with the
      environment, and in locomotion.

PMID- 29322529
TI  - Therapeutic action and aesthetic experience: Resonance and reorganization.
AB  - Is there an aesthetic dimension to therapeutic action? The author proposes that
      while the arts, in this example, dance, can serve as a bridge to give form and
      expression to the ineffable for both the artist and the observer, language,
      especially metaphorical language, in the context of a resonating therapeutic
      relationship, similarly gives form and enhanced meaning to what has been felt but
      not yet understood. Even if the content is painful, the process of mutually
      creating a common language that reorganizes the mind is aesthetically pleasing.

PMID- 29322528
TI  - MR and CT data with multiobserver delineations of organs in the pelvic area-Part
      of the Gold Atlas project.
AB  - PURPOSE: We describe a public dataset with MR and CT images of patients performed
      in the same position with both multiobserver and expert consensus delineations of
      relevant organs in the male pelvic region. The purpose was to provide means for
      training and validation of segmentation algorithms and methods to convert MR to
      CT like data, i.e., so called synthetic CT (sCT). ACQUISITION AND VALIDATION
      METHODS: T1- and T2-weighted MR images as well as CT data were collected for 19
      patients at three different departments. Five experts delineated nine organs for
      each patient based on the T2-weighted MR images. An automatic method was used to
      fuse the delineations. Starting from each fused delineation, a consensus
      delineation was agreed upon by the five experts for each organ and patient.
      Segmentation overlap between user delineations with respect to the consensus
      delineations was measured to describe the spread of the collected data. Finally,
      an open-source software was used to create deformation vector fields describing
      the relation between MR and CT images to further increase the usability of the
      dataset. DATA FORMAT AND USAGE NOTES: The dataset has been made publically
      available to be used for academic purposes, and can be accessed from
      https://zenodo.org/record/583096. POTENTIAL APPLICATIONS: The dataset provides a
      useful source for training and validation of segmentation algorithms as well as
      methods to convert MR to CT-like data (sCT). To give some examples: The T2
      weighted MR images with their consensus delineations can directly be used as a
      template in an existing atlas-based segmentation engine; the expert delineations
      are useful to validate the performance of a segmentation algorithm as they
      provide a way to measure variability among users which can be compared with the
      result of an automatic segmentation; and the pairwise deformably registered MR
      and CT images can be a source for an atlas-based sCT algorithm or for validation
      of sCT algorithm.

PMID- 29322531
TI  - A study to evaluate the primary causes associated with Pseudomonas otitis in 60
      dogs.
AB  - OBJECTIVES: To evaluate the primary causes, age of onset and time from diagnosis
      of otitis to development of Pseudomonas otitis in each case. MATERIALS AND
      METHODS: Data from clinical records of 60 dogs were extracted to address the
      study objectives. Pseudomonas otitis was diagnosed by clinical signs and positive
      culture. RESULTS: In total, 57 purebred dogs and three crossbreed dogs were
      included: 32 dogs had unilateral and 28 bilateral disease. Underlying primary
      causes of otitis were allergy (42), masses (8), endocrine disease (7) and
      autoimmune disease (3). The mean age of onset of otitis (and subsequent time to
      development of Pseudomonas otitis) in dogs with allergic otitis was 40 months (28
      months), with endocrine disease was 56 months (19 months) and masses 99 months
      (10 months). CLINICAL SIGNIFICANCE: The most common primary causes of otitis in
      dogs with Pseudomonas infections are, in decreasing frequency: allergies, masses,
      endocrine disease and autoimmune disease. Secondary infections with Pseudomonas
      developed more quickly if there was a mass or autoimmune disease, as compared
      with allergies and endocrinopathies.

PMID- 29322530
TI  - Chromium(III) release from chromium-tanned leather elicits allergic contact
      dermatitis: a use test study.
AB  - BACKGROUND: Chromium (Cr) is a common skin sensitizer. The use of Cr(VI) in
      leather is restricted in the EU, but that of Cr(III) is not. OBJECTIVES: To
      assess whether prolonged exposure to Cr-tanned leather with mainly Cr(III)
      release may elicit allergic contact dermatitis in Cr-allergic individuals.
      METHOD: Ten Cr-allergic subjects and 22 controls were patch tested with serial
      dilutions of Cr(III) and Cr(VI), and with leather samples. They then conducted a
      use test with a Cr-tanned and a Cr-free leather bracelet over a period of 3
      weeks, for 12 h per day. Cr deposited on the skin from the bracelets was measured
      in the controls, and the diphenylcarbazide test for Cr(VI) and extraction tests
      for Cr(III) and Cr(VI) were conducted for the different leathers. RESULTS: Four
      of 10 Cr-allergic subjects developed positive reactions to the Cr-tanned bracelet
      within 7-21 days, whereas only 1 of 10 had a positive patch test reaction to this
      leather. Cr released from the Cr-tanned leather was most probably entirely
      Cr(III), with a quantifiable amount being deposited on the skin. CONCLUSIONS:
      This study strongly suggests that prolonged and repeated exposure to Cr-tanned
      leather with mainly Cr(III) release is capable of eliciting allergic contact
      dermatitis in Cr-allergic individuals.

PMID- 29322533
TI  - Serenity: A subsystem quantum chemistry program.
AB  - We present the new quantum chemistry program Serenity. It implements a wide
      variety of functionalities with a focus on subsystem methodology. The modular
      code structure in combination with publicly available external tools and
      particular design concepts ensures extensibility and robustness with a focus on
      the needs of a subsystem program. Several important features of the program are
      exemplified with sample calculations with subsystem density-functional theory,
      potential reconstruction techniques, a projection-based embedding approach and
      combinations thereof with geometry optimization, semi-numerical frequency
      calculations and linear-response time-dependent density-functional theory. (c)
      2018 Wiley Periodicals, Inc.

PMID- 29322532
TI  - Factors associated with p-phenylenediamine sensitization: data from the
      Information Network of Departments of Dermatology, 2008-2013.
AB  - BACKGROUND: Risk factors for p-phenylenediamine (PPD) sensitization include the
      use of hair dyes, the application of temporary black henna tattoos, working as a
      hairdresser, and, possibly, exposure to hair dye pretests. OBJECTIVES: To
      quantify the impact of these (putative) risk factors on PPD sensitization.
      METHODS: Six items related to PPD exposure were added to the routine Information
      Network of Departments of Dermatology questionnaire from 2008 to 2013. A
      retrospective analysis of data from 4314 patients tested with PPD 1% pet. was
      conducted. RESULTS: Of the PPD-positive patients (n = 271), 80% had their hair
      dyed, and, of these, 57% subsequently developed scalp dermatitis, whereas only
      11% had had a henna tattoo. The self-administrated pretest with hair dye was
      performed by only a few patients, precluding a more detailed analysis. Hair
      dyeing [odds ratio (OR) 6.0; 95% confidence interval (CI): 3.9-9.4], henna
      tattoos (OR 2.4; 95%CI: 1.5-3.7) and being a hairdresser (OR 2.1; 95%CI: 1.3-3.2)
      increased the risk of PPD sensitization. Neither dyeing of own hair nor
      application of a temporary henna tattoo seemed to affect PPD sensitization in
      hairdressers. p-Aminoaryl compounds more often gave positive reactions in
      patients with henna tattoo. CONCLUSIONS: Hair dyeing is the major risk factor for
      PPD sensitization in this clinical setting, and application of a temporary black
      henna tattoo may also lead to (strong) PPD sensitization.

PMID- 29322534
TI  - Current controversies in prenatal diagnosis 1: All prenatally detected lower
      urinary tract obstructions should be shunted.

PMID- 29322535
TI  - Anatomy of the upper respiratory tract in domestic birds, with emphasis on
      vocalization.
AB  - This work reviews the anatomy of the upper respiratory tract in domestic birds
      including the chicken and pigeon. Non-exhaustive additional information on other
      bird species, illustrating the extraordinary diversity in the biological class
      Aves, can be found in several footnotes. The described anatomical structures are
      functionally considered in view of avian sound production. In particular, the
      Syrinx is invaluable. Its most important structures are the Labia and the lateral
      and medial tympaniform membranes in non-songbirds and songbirds, respectively.
      These structures produce sound by vibrating during expiration and eventually
      inspiration.

PMID- 29322536
TI  - Two-step estimation in ratio-of-mediator-probability weighted causal mediation
      analysis.
AB  - This study investigates appropriate estimation of estimator variability in the
      context of causal mediation analysis that employs propensity score-based
      weighting. Such an analysis decomposes the total effect of a treatment on the
      outcome into an indirect effect transmitted through a focal mediator and a direct
      effect bypassing the mediator. Ratio-of-mediator-probability weighting estimates
      these causal effects by adjusting for the confounding impact of a large number of
      pretreatment covariates through propensity score-based weighting. In step 1, a
      propensity score model is estimated. In step 2, the causal effects of interest
      are estimated using weights derived from the prior step's regression coefficient
      estimates. Statistical inferences obtained from this 2-step estimation procedure
      are potentially problematic if the estimated standard errors of the causal effect
      estimates do not reflect the sampling uncertainty in the estimation of the
      weights. This study extends to ratio-of-mediator-probability weighting analysis a
      solution to the 2-step estimation problem by stacking the score functions from
      both steps. We derive the asymptotic variance-covariance matrix for the indirect
      effect and direct effect 2-step estimators, provide simulation results, and
      illustrate with an application study. Our simulation results indicate that the
      sampling uncertainty in the estimated weights should not be ignored. The standard
      error estimation using the stacking procedure offers a viable alternative to
      bootstrap standard error estimation. We discuss broad implications of this
      approach for causal analysis involving propensity score-based weighting.

PMID- 29322537
TI  - Comparative evaluations of hypertrophic scar formation in in vivo models.
AB  - BACKGROUND AND OBJECTIVE: Hypertrophic scar (HTS) results from a connective
      tissue reaction to trauma, inflammation, surgery, or burn on skin. In spite of
      various techniques for wound generation, the degree of scar in animal models
      after healing is still unpredictable and less reproducible. The objective of the
      current study was to identify the appropriate method to create the maximal HTS
      tissue in a reliable manner by comparing three different methods in vivo.
      MATERIALS AND METHODS: A 27 ICR mice were tested for the in vivo evaluations.
      Three different methods were applied to develop wounds on the back of each mice
      for quantitative evaluations on collagen formation: Group 1 (thermal burn), Group
      2 (chemical burn), and Group 3 (physical punch). After injury, each lesion was
      photographed to examine physical variations in the wound areas. Histological
      analysis was conducted on days 0, 7, and 28 to assess the extent of the injury in
      the tissue and to quantitatively compare the amount of collagen formation after
      wound healing. RESULTS: Compared with Groups 1 and 3, Group 2 demonstrated the
      largest wound area that gradually decreased with healing time. However, the
      minimal axial damage (along tissue depth) occurred to Group 2 at day 0 (183.7 +/-
      28.9, 38.1 +/- 9.2, and 296.0 +/- 81.7 um for Groups 1, 2, and 3, respectively).
      After 28 days, all the groups showed the complete healing and accompanied a
      significant increase in the number of fibroblast and collagen generation with
      well-oriented and denser collagen fibers, in comparison with normal skin. Group 2
      yielded twice thicker skin (both epidermis and dermis) than the other groups
      (970.8 +/- 108.8 um for Group 2 vs. 381.5 +/- 30.8 um for Group 1 and 442.9 +/-
      56.3 um for Group 3; P < 0.001). CONCLUSION: The proposed chemical burn can be
      the optimal method to create collagenous scar tissue in the mouse model. Further
      in vivo investigations with rat models will be performed to validate the current
      technique for laser scar treatment in terms of reliability and
      immunohistochemical responses. Lasers Surg. Med. 9999:XX-XX, 2017. (c) 2017 Wiley
      Periodicals, Inc.

PMID- 29322538
TI  - Predicting reduction potentials of 1,3,6-triphenyl fulvenes using molecular
      electrostatic potential analysis of substituent effects.
AB  - The influence of mono- and multiple substituent effect on the reduction potential
      (E0 ) of 1,3,6-triphenyl fulvenes is investigated using B3LYP-SMD/6-311+G(d,p)
      level density functional theory. The molecular electrostatic potential (MESP)
      minimum at the fulvene pi-system (Vmin ) and the change in MESP at any of the
      fulvene carbon atoms (DeltaVC ) for both neutral and reduced forms are used as
      excellent measures of substituent effect from the para and meta positions of the
      1,3 and 6-phenyl moieties. Substitution at 6-phenyl para position has led to
      significant change in E0 than any other positions. By applying the additivity
      rule of substituent effects, an equation in DeltaVC is derived to predict E0 for
      multiply substituted fulvenes. Further, E0 is predicted for a set of 2000 hexa
      substituted fulvene derivatives where the substituents and their positions in the
      system are chosen in a random way. The calculated E0 agreed very well with the
      experimental E0 reported by Godman et al. Predicting E0 solely by substituent
      effect offers a simple and powerful way to select suitable combinations of
      substituents on fulvene system for light harvesting applications. (c) 2018 Wiley
      Periodicals, Inc.

PMID- 29322539
TI  - Inhaled corticosteroid use to prevent severe vaso-occlusive episode recurrence in
      children between 1 and 4 years of age with sickle cell disease: a multicenter
      feasibility trial.

PMID- 29322540
TI  - Review article: coeliac disease in later life must not be missed.
AB  - BACKGROUND: The presenting symptoms of coeliac disease are often subtle and the
      diagnosis is frequently delayed or overlooked. Therefore, especially elderly
      patients may be denied the benefits conferred by gluten free diet which can be
      dramatically life-changing. AIM: To review the occurrence, clinical features,
      diagnosis and management in coeliac patients detected later in life. METHODS: To
      review manuscripts concerned with coeliac disease in the elderly and to derive
      subgroups of elderly people from publications on the disorder. RESULTS:
      Approximately a quarter of all diagnoses are now made at the age of 60 years or
      more and a fifth at 65 years or over. About 4% are diagnosed at 80 years or
      above. Around 60% remain undetected, since their symptoms are often subtle:
      tiredness, indigestion, reduced appetite. Good compliance with gluten free diet,
      resolution of symptoms and improvement in laboratory indices can be achieved in
      over 90% of patients. CONCLUSIONS: Coeliac disease not uncommonly presents for
      the first time in older patients and is an important diagnosis to make.

PMID- 29322541
TI  - In case you missed it: The Prenatal Diagnosis editors bring you the most
      significant advances of 2017.

PMID- 29322542
TI  - A nonparametric method to detect increased frequencies of adverse drug reactions
      over time.
AB  - Signal detection is routinely applied to spontaneous report safety databases in
      the pharmaceutical industry and by regulators. As an example, methods that search
      for increases in the frequencies of known adverse drug reactions for a given drug
      are routinely applied, and the results are reported to the health authorities on
      a regular basis. Such methods need to be sensitive to detect true signals even
      when some of the adverse drug reactions are rare. The methods need to be specific
      and account for multiplicity to avoid false positive signals when the list of
      known adverse drug reactions is long. To apply them as part of a routine process,
      the methods also have to cope with very diverse drugs (increasing or decreasing
      number of cases over time, seasonal patterns, very safe drugs versus drugs for
      life-threatening diseases). In this paper, we develop new nonparametric signal
      detection methods, directed at detecting differences between a reporting and a
      reference period, or trends within a reporting period. These methods are based on
      bootstrap and permutation distributions, and they combine statistical
      significance with clinical relevance. We conducted a large simulation study to
      understand the operating characteristics of the methods. Our simulations show
      that the new methods have good power and control the family-wise error rate at
      the specified level. Overall, in all scenarios that we explored, the method
      performs much better than our current standard in terms of power, and it
      generates considerably less false positive signals as compared to the current
      standard.

PMID- 29322543
TI  - Effect of eptifibatide on inflammation during acute pain episodes in sickle cell
      disease.

PMID- 29322544
TI  - Role of bisphenol A as environmental factor in the promotion of non-alcoholic
      fatty liver disease: in vitro and clinical study.
AB  - BACKGROUND: Bisphenol A is an endocrine disrupting chemical associated with type
      2 diabetes mellitus (T2DM), cardiovascular disease and liver enzyme
      abnormalities. AIM: To evaluate bisphenol A plasma and urine levels in non
      alcoholic fatty liver disease (NAFLD) patients compared to healthy subjects.
      Furthermore, we evaluated, in human HepG2 cells, the effects of exposure to
      different concentrations of bisphenol A on both oxidative stress induction and
      cell proliferation. METHODS: We enrolled 60 patients with histological diagnosis
      of NAFLD with or without T2DM and sixty healthy subjects. In vitro, the
      proliferation of bisphenol A-exposed HepG2 cells at two different concentrations
      (0.025 and 0.05 MUM) was evaluated, both at high (H-HepG2) and at low (L-HepG2)
      glucose concentrations for 48 h. Lipoperoxidation was assessed by thiobarbituric
      acid reactive substances (TBARS) assay. RESULTS: Bisphenol A levels were
      significantly higher in 60 NAFLD subjects, both in urine and in plasma (P <
      0.0001) when compared to controls and, in this group, it appeared to be higher in
      30 non-alcoholic steatohepatitis patients compared to 30 simple steatosis
      subjects (P < 0.05), independently from the presence of T2DM. After a bisphenol A
      free diet for 1 month, NAFLD patients showed a significant reduction in bisphenol
      A circulating levels (P < 0.05), without a significant reduction in urine levels.
      H-HepG2 cells treated with bisphenol A (0.05 MUM) increased proliferation
      compared to controls at 48 h (P < 0.0001). Bisphenol A increased TBARS levels at
      48 h versus controls. CONCLUSIONS: Our study reveals a possible role of bisphenol
      A as an environmental factor involved in the promotion of NAFLD, particularly in
      T2DM patients.

PMID- 29322545
TI  - Acute toxicity of Corexit EC9500A and assessment of dioctyl sulfosuccinate as an
      indicator for monitoring four oil dispersants applied to diluted bitumen.
AB  - The present study investigated oil dispersant toxicity to fish species typical of
      the cooler regions of Canada, together with less well-documented issues
      pertaining to oil dispersant monitoring. The oil dispersant toxicity of Corexit
      EC9500A was assessed for the freshwater fish species rainbow trout and the
      seawater species coho, chinook, and chum, with a final median lethal
      concentration (LC50) acute lethality range between 35.3 and 59.8 mg/L. The LC50
      range was calculated using confirmed 0-h dispersant concentrations that were
      justified by fish mortality within the first 24 h of exposure and by variability
      of the dispersant indicator dioctyl sulfosuccinate (DOSS) used to monitor
      concentrations at later time points. To investigate DOSS as an oil dispersant
      indicator in the environment, microcosm systems were prepared containing Corexit
      EC9500A, Finasol OSR52, Slickgone NS, and Slickgone EW dispersants together with
      diluted bitumen. The DOSS indicator recovery was found to be stable for up to 13
      d at 5  degrees C, 8 d at 10  degrees C, but significantly less than 8 d at >=15 
      degrees C. After 3 d at temperatures >=15  degrees C, the DOSS indicator recovery
      became less accurate and was dependent on multiple environmental factors
      including temperature, microbial activity, and aeration, with potential for loss
      of solvents and stabilizers. A final assessment determined DOSS to be a
      discrepant indicator for long-term monitoring of oil dispersant in seawater.
      Environ Toxicol Chem 2018;37:1309-1319. (c) 2018 SETAC.

PMID- 29322546
TI  - Simulation of the effect of an external GHz electric field on the potential
      energy profile of Ca2+ ions in the selectivity filter of the CaV Ab channel.
AB  - CaV channels are transmembrane proteins that mediate and regulate ion fluxes
      across cell membranes, and they are activated in response to action potentials to
      allow Ca2+ influx. Since ion channels are composed of charge or polar groups, an
      external alternating electric field may affect the ion-selective membrane
      transport and the performance of the channel. In this article, we have
      investigated the effect of an external GHz electric field on the dynamics of
      calcium ions in the selectivity filter of the CaV Ab channel. Molecular dynamics
      (MD) simulations and the potential of mean force (PMF) calculations were carried
      out, via the umbrella sampling method, to determine the free energy profile of
      Ca2+ ions in the CaV Ab channels in presence and absence of an external field.
      Exposing CaV Ab channel to 1, 2, 3, 4, and 5 GHz electric fields increases the
      depth of the potential energy well and this may result in an increase in the
      affinity and strength of Ca2+ ions to binding sites in the selectivity filter the
      channel. This increase of strength of Ca2+ ions binding in the selectivity filter
      may interrupt the mechanism of Ca2+ ion conduction, and leads to a reduction of
      Ca2+ ion permeation through the CaV Ab channel.

PMID- 29322547
TI  - Improvement of the salvage-rate of flap after venous thrombosis with
      intraparenchymatous venous pressure monitoring.
AB  - PURPOSE: Intraparenchymatous venous pressure (IVP) monitoring in flap can measure
      venous pressure with catheter placement. Among patients with IVP monitoring, this
      study reviewed postoperative microvascular complications for investigating the
      transplanted-tissue salvage-rate. PATIENTS AND METHODS: Two hundred and seventy
      one patients (male, 132; female, 139; mean age, 52.3 years; age range, 9-82
      years) underwent free flap transfer and postoperative continuous IVP monitoring,
      which performed as follows; a venous catheter was connected to a transducer, and
      venous pressure in the flap was recorded for three consecutive days
      postoperatively. The threshold of alarm for elevated venous pressure was set at
      50 mm Hg. When abnormal measurements or fluctuation were observed, the vascular
      anastomotic site was exposed immediately. The flap salvage-rate of non-IVP
      monitoring group (n = 393; male, 305; female, 81; mean age, 61.3 years; age
      range, 23-83 years), which were confirmed by a portable ultrasonographic device,
      was compared with that of IVP-monitoring group. RESULTS: Twenty-one patients
      developed postoperative microvascular complications at the vascular anastomosis
      sites. Sensitivity rate of IVP monitoring was 86%; specificity rate, 96%;
      positive predictive value rates, 64%; negative predictive value rate, 99%; false
      positive rate, 4%. The flap salvage-rate was 83% in venous thrombosis cases and
      only 33% in arterial thrombosis cases. In non-IVP monitoring group, flap salvage
      rate was 20% with arterial thrombosis and 36% with venous thrombosis, resulting
      in an increasing the salvage-rate (P = .021). CONCLUSIONS: IVP monitoring could
      visualize and quantify venous pressure waves in flap and detect early
      microvascular complications, resulting in a marked improvement in the graft
      tissue salvage-rate.

PMID- 29322548
TI  - Validation study of the hoehn and yahr scale included in the MDS-UPDRS.

PMID- 29322549
TI  - Noise properties of proton density fat fraction estimated using chemical shift
      encoded MRI.
AB  - PURPOSE: The purpose of this work is to characterize the noise distribution of
      proton density fat fraction (PDFF) measured using chemical shift-encoded MRI, and
      to provide alternative strategies to reduce bias in PDFF estimation. THEORY: We
      derived the probability density function for PDFF estimated using chemical shift
      encoded MRI, and found it to exhibit an asymmetric noise distribution that
      contributes to signal-to-noise-ratio dependent bias. METHODS: To study PDFF noise
      bias, we performed (at 1.5 T) numerical simulations, phantom acquisitions, and a
      retrospective in vivo experiment. In each experiment, we compared the performance
      of three statistics (mean, median, and maximum likelihood estimator) in
      estimating the PDFF in a region of interest. RESULTS: We demonstrated the
      presence of the asymmetric noise distribution in simulations, phantoms, and in
      vivo. In each experiment we demonstrated that both the median and proposed
      maximum likelihood estimator statistics outperformed the mean statistic in
      mitigating noise-related bias for low signal-to-noise-ratio acquisitions.
      CONCLUSIONS: Characterization of the noise distribution of PDFF estimated using
      chemical shift-encoded MRI enabled new strategies based on median and maximum
      likelihood estimator statistics to mitigate noise-related bias for accurate PDFF
      measurement from a region of interest. Such strategies are important for
      quantitative chemical shift-encoded MRI applications that typically operate in
      low signal-to-noise-ratio regimes. Magn Reson Med 80:685-695, 2018. (c) 2018
      International Society for Magnetic Resonance in Medicine.

PMID- 29322550
TI  - Hyposalivation and 10-year all-cause mortality in an elderly Japanese population.
AB  - OBJECTIVE: To evaluate the association of salivary flow rate with all-cause
      mortality among older Japanese adults. We hypothesised that hyposalivation would
      be a marker for mortality. BACKGROUND: Hyposalivation, which is an objectively
      measurable decrease in salivary flow, is highly prevalent among older adults. It
      is associated with malnutrition and poor general health. METHODS: The study
      population comprised 600 community-dwelling Japanese adults (306 men and 294
      women), who were 70 years old at baseline. They underwent stimulated salivary
      flow rate (SSFR) measurements and were followed up during a 10-year study period.
      After stratification by sex, the hazard ratios of all-cause mortality were
      estimated using Cox proportional hazards regression analysis comparing groups
      with and without hyposalivation (ie, SSFR < 0.7 mL/min). RESULTS: The baseline
      prevalence of hyposalivation was 27.8% (85/306) among men and 47.3% (139/294)
      among women. During a mean (standard deviation) follow-up period of 104 (27)
      months, 80 deaths occurred: 60 (75.0%) deaths among men and 20 (25.0%) deaths
      among women. After adjusting for the number of remaining teeth, smoking status,
      exercise, hypoalbuminemia, diabetes and cardiovascular disease, hyposalivation at
      baseline was significantly associated with all-cause mortality among men
      (adjusted hazard ratio, 1.71; 95% confidence interval, 1.01-2.89). In contrast,
      no association between SSFR and all-cause mortality existed among women.
      CONCLUSION: Hyposalivation could be a marker for all-cause mortality among older
      community-dwelling Japanese men. Future studies investigating the association
      between SSFR and cause-specific mortality are warranted.

PMID- 29322552
TI  - Gene-gene and gene-environment interactions in complex traits in yeast.
AB  - One of the fundamental questions in biology is how the genotype regulates the
      phenotype. An increasing number of studies indicate that, in most cases, the
      effect of a genetic locus on the phenotype is context-dependent, i.e. it is
      influenced by the genetic background and the environment in which the phenotype
      is measured. Still, the majority of the studies, in both model organisms and
      humans, that map the genetic regulation of phenotypic variation in complex traits
      primarily identify additive loci with independent effects. This does not reflect
      an absence of the contribution of genetic interactions to phenotypic variation,
      but instead is a consequence of the technical limitations in mapping gene-gene
      interactions (GGI) and gene-environment interactions (GEI). Yeast, with its
      detailed molecular understanding, diverse population genomics and ease of genetic
      manipulation, is a unique and powerful resource to study the contributions of GGI
      and GEI in the regulation of phenotypic variation. Here we review studies in
      yeast that have identified GGI and GEI that regulate phenotypic variation, and
      discuss the contribution of these findings in explaining missing heritability of
      complex traits, and how observations from these GGI and GEI studies enhance our
      understanding of the mechanisms underlying genetic robustness and adaptability
      that shape the architecture of the genotype-phenotype map.

PMID- 29322551
TI  - Improving parallel imaging by jointly reconstructing multi-contrast data.
AB  - PURPOSE: To develop parallel imaging techniques that simultaneously exploit coil
      sensitivity encoding, image phase prior information, similarities across multiple
      images, and complementary k-space sampling for highly accelerated data
      acquisition. METHODS: We introduce joint virtual coil (JVC)-generalized
      autocalibrating partially parallel acquisitions (GRAPPA) to jointly reconstruct
      data acquired with different contrast preparations, and show its application in
      2D, 3D, and simultaneous multi-slice (SMS) acquisitions. We extend the joint
      parallel imaging concept to exploit limited support and smooth phase constraints
      through Joint (J-) LORAKS formulation. J-LORAKS allows joint parallel imaging
      from limited autocalibration signal region, as well as permitting partial Fourier
      sampling and calibrationless reconstruction. RESULTS: We demonstrate highly
      accelerated 2D balanced steady-state free precession with phase cycling, SMS
      multi-echo spin echo, 3D multi-echo magnetization-prepared rapid gradient echo,
      and multi-echo gradient recalled echo acquisitions in vivo. Compared to
      conventional GRAPPA, proposed joint acquisition/reconstruction techniques provide
      more than 2-fold reduction in reconstruction error. CONCLUSION: JVC-GRAPPA takes
      advantage of additional spatial encoding from phase information and image
      similarity, and employs different sampling patterns across acquisitions. J-LORAKS
      achieves a more parsimonious low-rank representation of local k-space by
      considering multiple images as additional coils. Both approaches provide dramatic
      improvement in artifact and noise mitigation over conventional single-contrast
      parallel imaging reconstruction. Magn Reson Med 80:619-632, 2018. (c) 2018
      International Society for Magnetic Resonance in Medicine.

PMID- 29322553
TI  - Systematic reviews versus narrative reviews in clinical anatomy: Methodological
      approaches in the era of evidence-based anatomy.
AB  - Two main types of review articles with distinct characteristics and goals are
      commonly found in the scientific literature: systematic reviews and narrative
      (also called expert or traditional) reviews. Narrative reviews are publications
      that describe and discuss the state of science on a specific topic or theme from
      a theoretical and contextual point of view with little explicit structure for
      gathering and presenting evidence. Systematic reviews are overviews of the
      literature undertaken by identifying, critically appraising and synthesizing the
      results of primary research studies using an explicit methodological approach.
      With the recent rise of evidence-based anatomy, important questions arise with
      respect to the utility of narrative reviews in clinical anatomy. The goal of this
      perspective article is to address the key differences between narrative and
      systematic reviews in the context of clinical anatomy, to provide guidance on
      which type of review is most appropriate for a specific issue, and to summarize
      how the two types of reviews can work in unison to enhance the quality of
      anatomical research and its delivery to clinicians and anatomists alike. Clin.
      Anat. 31:364-367, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 29322554
TI  - Transcription factor Foxc1 is involved in anterior part of cranial base
      formation.
AB  - The cranial base is a structure mainly formed through endochondral ossification
      and integrated into the craniofacial complex, which acts as an underlying
      platform for the developing brain. Foxc1 is an indispensable regulator during
      intramembranous and endochondral ossification. In this study, we found that the
      spontaneous loss of Foxc1 function in a mouse (congenital hydrocephalous),
      Foxc1ch/ch , demonstrated the anterior cranial base defects, including unossified
      presphenoid and lack of middle part of the basisphenoid bone. Hypoplastic
      presphenoid primordial cartilage (basal portion of the trabecular cartilage
      [bTB]) and a lack of the middle part of basisphenoid primordial cartilage (the
      hypophyseal cartilage) were consistently observed at earlier developmental stage.
      Foxc1 was expressed robustly and ubiquitously in undifferentiated mesenchyme of
      the cranial base-forming area in E11.0 wild-type fetuses. Once chondrogenesis
      commenced, the expression was downregulated and later limited to the
      perichondrium. Detection of transcripts of Collagen type2 A1 (Col2a1) revealed
      that both bTB and the anterior part of the hypophyseal cartilage developing
      anterior to the persistent epithelial stalk of the anterior lobe of the pituitary
      gland were suppressed in the Foxc1ch/ch . Proliferation activity of chondrocyte
      precursor cells was higher in the Foxc1ch/ch . Loss of Foxc1 function only in the
      neural crest cell lineage (Wnt1-cre;Foxc1ch/flox ) showed ossification of the
      posterior part of the hypophyseal cartilage derived from the mesoderm. These
      findings suggest that Foxc1 is an important regulator to further chondrogenesis
      and initiate the ossification of the presphenoid and basisphenoid bones.

PMID- 29322555
TI  - Evaluating Factors Impacting Medication Adherence Among Rural, Urban, and
      Suburban Populations.
AB  - PURPOSE: To evaluate differences in prescription medication adherence rates, as
      well as influencing factors, in rural and urban adults. METHODS: This is a
      retrospective analysis of the 2015 National Consumer Survey on the Medication
      Experience and Pharmacists' Role. A total of 26,173 participants completed the
      survey and provided usable data. Participants using between 1 and 30 prescription
      medications and living more than 0 miles and up to 200 miles from their nearest
      pharmacy were selected for the study, resulting in a total of 15,933
      participants. Data from the 2010 US Census and Rural Health Research Center were
      used to determine the population density of each participant's ZIP code.
      Participant adherence to reported chronic medications was measured based on the 8
      item Morisky Medication Adherence Scale (MMAS-8). FINDINGS: Overall adherence
      rates did not differ significantly between rural and urban adults with average
      adherence based on MMAS-8 scores of 5.58 and 5.64, respectively (P = .253). Age,
      income, education, male sex, and white race/ethnicity were associated with higher
      adherence rates. While the overall adherence rates between urban and rural adults
      were not significantly different, the factors that influenced adherence varied
      between age-specific population density groupings. CONCLUSION: These analyses
      suggest that there is no significant difference in adherence between rural and
      urban populations; however, the factors contributing to medication adherence may
      vary based on age and population density. Future adherence intervention methods
      should be designed with consideration for these individualized factors.

PMID- 29322556
TI  - Relationships between lewy and tau pathologies in 375 consecutive non-Alzheimer's
      olfactory bulbs.

PMID- 29322558
TI  - "The Masks We Wear": A Qualitative Study of Suicide in Australian Farmers.
AB  - PURPOSE: Farmer suicide is a major public issue in Australia. Using the
      psychological autopsy method, this study aimed to examine the life and death
      circumstances of Australian male farmers who died by suicide through verbal
      reports from their close significant others. METHODS: Individual semistructured
      interviews were conducted with 12 relatives of male farmers who had died by
      suicide in Queensland or New South Wales, Australia (2006-2014). This study
      followed the COREQ checklist criteria for the reporting of qualitative research.
      FINDINGS: Six interrelated themes were identified: (1) masculinity, (2)
      uncertainty and lack of control in farming, (3) feelings of failure in
      relationships and farming, (4) escalating health problems, (5) maladaptive
      coping, and (6) acquired capability with access to means. CONCLUSIONS: Effective
      clinical interventions, as well as suicide prevention strategies, need to
      consider the importance of 3 key issues in suicide among farmers: adherence to
      masculine norms and socialization; expectations of self in maintaining family
      traditions and occupation; and a male subtype of depression.

PMID- 29322557
TI  - Veni, vidi, vici: the success of wtf meiotic drivers in fission yeast.
AB  - Meiotic drivers are selfish DNA loci that can bias their own transmission into
      gametes. Owing to their transmission advantages, meiotic drivers can spread in
      populations even if the drivers or linked variants decrease organismal fitness.
      Meiotic drive was first formally described in the 1950s and is thought to be a
      powerful force shaping eukaryotic genomes. Classic genetic analyses have detected
      the action of meiotic drivers in plants, filamentous fungi, insects and
      vertebrates. Several of these drive systems have limited experimental
      tractability and relatively little is known about the molecular mechanisms of
      meiotic drive. Recently, however, meiotic drivers were discovered in a yeast
      species. The Schizosaccharomyces pombe wtf gene family contains several active
      meiotic drive genes. This review summarizes what is known about the wtf family
      and highlights its potential as a highly tractable experimental model for
      molecular and evolutionary characterization of meiotic drive.

PMID- 29322559
TI  - CEST-Dixon for human breast lesion characterization at 3 T: A preliminary study.
AB  - PURPOSE: Chemical exchange saturation transfer (CEST) MRI for breast lesion
      characterization is promising. However, artifacts are prone to develop in breast
      CEST imaging as a result of strong lipid signals. The aims of the study are (i)
      to develop and validate the CEST-Dixon imaging sequence for simultaneous water
      fat separation and B0 mapping; and (ii) use the CEST-Dixon method to characterize
      suspicious lesions in patients undergoing percutaneous biopsy. METHODS: The
      gradient-echo multi-echo Dixon acquisition is used to create fat-free CEST and B0
      maps. The sequence has been validated in phantoms and in vivo. Five healthy
      volunteers and 10 patients were scanned to compare the CEST contrast in three
      frequency ranges centered at 1, 2, and 3.5 ppm. The correlation between the CEST
      contrast and pathology markers (tumor type, estrogen receptor (ER) status, and Ki
      67) was also investigated by stratifying the patients into ER-negative invasive
      ductal carcinoma (IDC) (more aggressive), ER-positive IDC (less aggressive), and
      benign groups. RESULTS: The CEST-Dixon sequence shows homogenous fat removal in
      the water-only images. The ER-negative IDC tissues display a trend to higher CEST
      contrast in all three frequency ranges, whereas the ER-positive IDC, benign, and
      normal tissues have lower CEST contrast. No significant differences were observed
      among the ER-positive IDC, benign, and normal tissues. Of the three frequencies
      ranges, the CEST contrasts at 1 ppm are high in the ER-negative IDC group, have
      the largest difference among the ER-negative IDC and the other groups, and have
      the highest correlation with Ki-67. CONCLUSION: Breast CEST-Dixon imaging shows
      potential to differentiate more aggressive from less aggressive cancers. Magn
      Reson Med 80:895-903, 2018. (c) 2018 International Society for Magnetic Resonance
      in Medicine.

PMID- 29322560
TI  - Fast nonlinear susceptibility inversion with variational regularization.
AB  - PURPOSE: Quantitative susceptibility mapping can be performed through the
      minimization of a function consisting of data fidelity and regularization terms.
      For data consistency, a Gaussian-phase noise distribution is often assumed, which
      breaks down when the signal-to-noise ratio is low. A previously proposed
      alternative is to use a nonlinear data fidelity term, which reduces streaking
      artifacts, mitigates noise amplification, and results in more accurate
      susceptibility estimates. We hereby present a novel algorithm that solves the
      nonlinear functional while achieving computation speeds comparable to those for a
      linear formulation. METHODS: We developed a nonlinear quantitative susceptibility
      mapping algorithm (fast nonlinear susceptibility inversion) based on the variable
      splitting and alternating direction method of multipliers, in which the problem
      is split into simpler subproblems with closed-form solutions and a decoupled
      nonlinear inversion hereby solved with a Newton-Raphson iterative procedure. Fast
      nonlinear susceptibility inversion performance was assessed using numerical
      phantom and in vivo experiments, and was compared against the nonlinear
      morphology-enabled dipole inversion method. RESULTS: Fast nonlinear
      susceptibility inversion achieves similar accuracy to nonlinear morphology
      enabled dipole inversion but with significantly improved computational
      efficiency. CONCLUSION: The proposed method enables accurate reconstructions in a
      fraction of the time required by state-of-the-art quantitative susceptibility
      mapping methods. Magn Reson Med 80:814-821, 2018. (c) 2018 International Society
      for Magnetic Resonance in Medicine.

PMID- 29322562
TI  - Pure 21q22.3 deletion identified in a patient with mild phenotypic features.

PMID- 29322561
TI  - Effect of an oxygen-generating scaffold on the viability and insulin secretion
      function of porcine neonatal pancreatic cell clusters.
AB  - BACKGROUND: Islet encapsulation techniques have shown limited success in
      maintaining islet survival and function because encapsulation decreases oxygen
      supply. In this study, an oxygen-generating scaffold was fabricated to prevent
      hypoxic cell damage and improve the viability and insulin secretion of islets.
      METHODS: We fabricated an oxygen-generating scaffold by mixing calcium peroxide
      (CaO2 ) with polydimethylsiloxane (PDMS). We evaluated the effects of the oxygen
      generating PDMS + CaO2 scaffold on viability, caspase-3 and caspase-7 activity,
      oxygen consumption rate (OCR), glucose-stimulated insulin secretion (GSIS),
      hypoxic cell marker expression, and reactive oxygen species (ROS) levels in
      porcine neonatal pancreatic cell clusters (NPCCs). We also fabricated a
      microfluidic device that allowed measuring the effects of the oxygen-generating
      scaffold on viability. RESULTS: Oxygen generation by the PDMS + CaO2 scaffold was
      sustained for more than 24 hours in vitro. NPCCs encapsulated in PDMS + CaO2
      showed higher viability than NPCCs in PDMS scaffolds and control NPCCs grown
      without a scaffold. PDMS + CaO2 -encapsulated NPCCs showed lower caspase-3 and
      caspase-7 activity, hypoxic cell expression, and ROS levels, and higher OCR and
      GSIS than those in PDMS or control cells. Using the microfluidic device, we
      observed that the viability of PDMS + CaO2 -encapsulated NPCCs was higher than
      that of PDMS-encapsulated NPCCs. CONCLUSIONS: NPCCs in PDMS + CaO2 scaffolds show
      higher viability and insulin secretion than do NPCCs in PDMS scaffolds and
      control cells. Therefore, this oxygen-generating scaffold has potential for
      application in future islet transplantation studies.

PMID- 29322563
TI  - Microfluidics-based LC-MS MRM approach for the relative quantification of
      Burkholderia cenocepacia secreted virulence factors.
AB  - Burkholderia cenocepacia is an opportunistic pathogen that is commonly isolated
      from patients with cystic fibrosis (CF). Several virulence factors have been
      identified, including extracellular enzymes that are secreted by type II and type
      VI secretion systems. The activity of these secretion systems is modulated by
      quorum sensing. Apart from the classical acylhomoserine lactone quorum sensing,
      B. cenocepacia also uses the diffusible signal factor system (DSF) i.e. 2
      undecenoic acid derivatives that are recognized by specific receptors resulting
      in changes in biofilm formation, motility and virulence. However, quantitative
      information on alterations in the actual production and release of virulence
      factors upon exposure to DSF is lacking. We here describe an approach
      implementing microfluidics based chromatography combined with single reaction
      monitoring to quantify protein virulence factors in the secretome of B.
      cenocepacia.

PMID- 29322564
TI  - Can fortified foods and snacks increase the energy and protein intake of
      hospitalised older patients? A systematic review.
AB  - BACKGROUND: Undernutrition affects over 44% of hospitalised older people, who
      often dislike oral nutritional supplements (ONS). This review summarises the
      evidence for an alternative strategy, using energy and protein dense meals (via
      fortification) or snacks (supplementation) to increase the dietary energy and
      protein intake of older inpatients. METHODS: A search was conducted through
      PubMed, EMBASE, CINAHL and the Cochrane database of systematic reviews (May 1996
      to May 2016) that used fortification or supplementation to increase the energy or
      protein intake of patients (mean age >=60 years) in hospitals or rehabilitation
      centres. RESULTS: Ten articles (546 patients, mean age 60-83 years) were
      identified. Compared with usual nutritional care, six studies using either energy
      or protein based fortification and supplementation significantly increased intake
      of energy (250-450 kcal day-1 ) or protein (12-16 g day-1 ). Two studies enriched
      menus with both energy and protein, and significantly increased both energy (698
      kcal day-1 and 21 kJ kg-1 ) and protein (16 g and 0.2 g kg-1 ) intake compared to
      usual care. ONS was similar to supplementation in one study but superior to
      fortification in another. Four studies reported good acceptability of enriched
      products and two studies that found they were cost-effective. CONCLUSIONS:
      Compared with usual nutritional care, energy- and protein-based fortification and
      supplementation could be employed as an effective, well-tolerated and cost
      effective intervention to improve dietary intake amongst older inpatients. This
      strategy may be particularly useful for patients with cognitive impairment who
      struggle with ONS, and clinical trials are required to compare these approaches
      and establish their impact on functional outcomes.

PMID- 29322565
TI  - On the Variable Reactivity of Phosphine-Functionalized [Ge9 ] Clusters: Zintl
      Cluster-Substituted Phosphines or Phosphine-Substituted Zintl Clusters.
AB  - The reaction of [(Ge9 {Si(TMS)3 }2 PtBu2 )]- with NHCMes CuCl yields [(Ge9
      {Si(TMS)3 }2 )(tBu2 P)]Cu(NHCMes ) (1), which is a new derivative of the recently
      reported monomeric zwitterionic tetrel cluster compounds [(Ge9 {Si(TMS)3 }2
      )(tBu2 P)]M(NHCDipp ) (M: Cu, Ag, Au). By contrast, the reaction of the same
      anion [(Ge9 {Si(TMS)3 }2 PtBu2 )]- with the more labile copper phosphine complex
      Cy3 PCuCl leads to the formation of [Ge9 {Si(TMS)3 }2 {(tBu)2 PCu}2 Ge9 {Si(TMS)3
      }2 ] (2), which is a neutral dimeric twofold-bridged [Ge9 ] cluster compound,
      with the exo-bonded phosphine substituent being involved in the cluster bridging.
      In case of the presence of sterically more demanding phosphines in [Ge9 {Si(TMS)3
      }2 PR2 ]- [R: Mes (3) and NiPr2 (4)], reactions with NHCDipp CuCl yielded the
      complexes NHCDipp Cu[eta3 -Ge9 {Si(TMS)3 }2 (PR2 )] [R: Mes (5) and NiPr2 (6)],
      comprising exclusively Cu-Ge bonds. Compounds 5 and 6 show varying reactivity in
      dependence of the identity of the phosphine group and represent the first
      examples of fourfold-substituted [Ge9 ] clusters with three different ligands
      bound to the [Ge9 ] cluster core. All compounds were characterized by 1 H, 13 C,
      31 P, and 29 Si NMR spectroscopy. Additionally, compounds 3 and 4 were analyzed
      by ESI-MS, and the structures of compounds 1, 2, and 5 were characterized by
      single-crystal X-ray diffraction.

PMID- 29322566
TI  - Nursing a media grievance.

PMID- 29322567
TI  - Oral delivery system enhanced the bioavailability of stilbenes: Resveratrol and
      pterostilbene.
AB  - Stilbenes are a large group of compounds with the C6 ?C2 ?C6 skeleton, in which
      two aromatic rings are connected by an ethylene bridge. Resveratrol and its
      structural analog, pterostilbene, are by far the two most widely researched
      stilbenes in terms of their beneficial bioactivities. However, the bioefficacy of
      these compounds is greatly reduced when consumed orally due to their poor aqueous
      solubility, which leads to poor bioavailability. To overcome the limitation,
      strategies improving their solubility, absorption, and systemic concentration
      were applied when designing a suitable edible delivery system. This review will
      summarize the findings from the studies evaluating the oral bioavailability of
      stilbenes with emphasize on the resveratrol and pterostilbene. It will also
      include the edible delivery systems currently available and their effect on the
      oral bioavailability. (c) 2018 BioFactors, 44(1):5-15, 2018.

PMID- 29322568
TI  - Energy Transfer in Supramolecular Heteronuclear Lanthanide Dimers and Application
      to Fluoride Sensing in Water.
AB  - In the presence of fluoride anions, [LnL(H2 O)]+ complexes, based on the
      coordination of a lanthanide (Ln) cation into the cavity of a C2v symmetrical
      cyclen-based ligand (L), self-assemble in water to form [(LnL)2 F]+ dimers. The
      crystal structures of the Yb hydrated monomer and of the fluorinated dimer are
      reported and analyzed to unravel the impact of the cumulative effect of weak
      hydrogen bonding and aromatic stacking interactions in the supramolecular
      assembly. The assembly is stable over a broad range of pH 3-8. A combination of
      equimolar amounts of Eu and Tb complexes led to a quasistatistical mixture of
      homo- and heterodimers, as observed by using electrospray mass spectrometry. In
      the heterodimers, selective excitation into the 7 F6 ->5 D4 absorption band of
      the Tb center at lambda=488 nm allowed the observation of a Tb-to-Eu downshifting
      energy transfer, not observed in the absence of fluoride ions. Analysis of the
      excited-state lifetimes of the dimers within the frame of the Forster theory of
      energy transfer showed the transfer to have an efficiency of 34 %, with a
      corresponding Forster radius of 4.1 A; thereby, unraveling the short Ln-Ln
      distance as a crucial parameter of the energy-transfer process. By using
      equimolar mixtures of the Tb and Eu complexes, the energy-transfer phenomenon was
      used for a ratiometric sensing of fluoride anions in water with a detection limit
      of 17.7 nm.

PMID- 29322569
TI  - A Copper(II) Molecular Catalyst for Efficient and Selective Photochemical
      Reduction of CO2 to CO in a Water-Containing System.
AB  - A catalyst developed from a CuII complex of (Et4 N)[Cu(pyN2Me2 )(HCO2 )]?0.5 CH3
      OH?H2 O (1?0.5 CH3 OH?H2 O; pyN2Me2 =bis(2,6-dimethylphenyl)-2,6
      pyridinedicarboxamidate(2-)) shows a high activity to catalyze the reduction
      reaction of CO2 to CO driven by visible light in 4:1 acetonitrile/water (v:v)
      using [Ru(phen)3 ](PF6 )2 as photosensitizer and TEOA as sacrificial reductant,
      with a high TON of 9900 and a high CO selectivity of 98 %. The results of isotope
      labeling experiment, durability tests and energy dispersive spectroscopy reveal
      that 1 is robust during the photocatalytic process.

PMID- 29322570
TI  - Two-Pot Synthesis of Chiral 1,3-syn-Diols through Asymmetric Organocatalytic
      Aldol and Wittig Reactions Followed by Domino Hemiacetal/Oxy-Michael Reactions.
AB  - A two-pot synthetic method to construct the chiral syn-1,3-diol unit has been
      developed from three aldehydes and either Wittig or Horner-Wadsworth-Emmons
      reagents. In the first pot, chiral delta-hydroxy alpha,beta-unsaturated ketones
      are synthesized with excellent enantioselectivity by the organocatalyst-mediated
      asymmetric direct aldol reaction of two different aldehydes, followed by either
      Wittig or Horner-Wadsworth-Emmons reactions. In the second pot, domino
      acetalization with an aldehyde and subsequent oxy-Michael reaction proceeds in
      the presence of NaClO4 and a catalytic amount of Bi(OTf)3
      (OTf=trifluoromethanesulfonate) to provide the chiral 1,3-syn-diol derivative
      with excellent diastereoselectivity. Diospongin C and yashabushidiol A have been
      synthesized efficiently by using the present method as a key step.

PMID- 29322571
TI  - Selective Single-Site Pd-In Hydrogenation Catalyst for Production of Enhanced
      Magnetic Resonance Signals using Parahydrogen.
AB  - Pd-In/Al2 O3 single-site catalyst was able to show high selectivity (up to 98 %)
      in the gas phase semihydrogenation of propyne. Formation of intermetallic Pd-In
      compound was studied by XPS during reduction of the catalyst. FTIR-CO
      spectroscopy confirmed single-site nature of the intermetallic Pd-In phase
      reduced at high temperature. Utilization of Pd-In/Al2 O3 in semihydrogenation of
      propyne with parahydrogen allowed to produce ~3400-fold NMR signal enhancement
      for reaction product propene (polarization=9.3 %), demonstrating the large
      contribution of pairwise hydrogen addition route. Significant signal enhancement
      as well as the high catalytic activity of the Pd-In catalyst allowed to acquire 1
      H MR images of flowing hyperpolarized propene gas selectively for protons in CH,
      CH2 and CH3 groups. This observation is unique and can be easily transferred to
      the development of a useful MRI technique for an in situ investigation of
      selective semihydrogenation in catalytic reactors.

PMID- 29322573
TI  - Narrow band imaging versus laryngovideostroboscopy in precancerous and malignant
      vocal fold lesions.
AB  - BACKGROUND: This is a comparative analysis of the diagnostic accuracy of narrow
      band imaging (NBI) and laryngovideostroboscopy (LVS) in the assessment of
      premalignant and malignant vocal fold lesions. METHODS: A prospective analysis
      was performed on 105 consecutive patients with vocal fold lesions. The NBI and
      LVS were obtained before the microsurgery. RESULTS: The NBI and LVS showed no
      significant differences in identifying premalignant and malignant pathologies.
      However, in analysis restricted to identification of only malignant lesions, the
      specificity (88.9% vs 20.6%), accuracy (90.5% vs 51.4%), and positive predictive
      value (PPV; 84.8% vs 45.1%) were significantly higher for NBI (P value < .001;
      .015; and .045, respectively). A comparison of LVS scored results relative to
      each NBI type revealed statistically significant differences (P < .001). A
      moderate positive correlation between NBI and LVS was demonstrated (P = .54).
      CONCLUSION: The NBI and LVS are useful, complementary tools in evaluating early
      potential vocal fold malignancies. The NBI was superior to LVS on several
      statistical analyses.

PMID- 29322572
TI  - Burnout among direct-care workers in nursing homes: Influences of organisational,
      workplace, interpersonal and personal characteristics.
AB  - AIMS AND OBJECTIVES: The many negative effects of burnout have prompted
      researchers to better understand the factors contributing to it. The purpose of
      this paper is to add to this body of knowledge through the study of burnout among
      direct-care workers in nursing homes. BACKGROUND: Perhaps the factor most often
      associated with employee burnout is the level of staffing-insufficient staffing
      results in work overload and eventually employee burnout. A closer look at
      research findings suggests that there are many other factors also contributing to
      burnout. These range from those at the organisational level, such as availability
      of training and resources to individual characteristics such as self-esteem and
      length of employment. METHODS: A self-administered survey instrument was
      completed by 410 direct-care workers working within 11 nursing homes in the north
      Texas region. Regression analyses were performed, adjusting for clustering by
      nursing home. Beta coefficients and structure coefficients are reported. Burnout
      was measured through three dimensions: emotional exhaustion, depersonalisation
      and personal accomplishment. RESULTS: Organisational, work design, interpersonal
      and individual characteristics were found to be associated with one or more
      dimensions of burnout. CONCLUSIONS: The analyses largely support previous
      research. Organisational variables of significance included the availability of
      resources to do the work, available training and fair pay. Work design variables
      of significance included adequate staffing. The individual characteristic, self
      esteem, appeared to have the strongest impact on burnout. Commitment to the
      organisation also had a large impact. RELEVANCE TO CLINICAL PRACTICE: While the
      data do not allow for the testing of causal relationships, the data do suggest
      that providing adequate staffing, perceived fair pay, sufficient work resources
      (e.g., towels, gowns), management support and adequate training may result in
      less direct-care worker burnout on the job.

PMID- 29322574
TI  - Effects of sleep on the realization of complex plans.
AB  - Sleep consolidates newly encoded memories, particularly those memories that are
      relevant for future behaviour. This study explored whether sleep facilitates the
      successful execution of relatively complex plans in the future. We applied the
      Dresden Breakfast Task, in which subjects are instructed to prepare a virtual
      breakfast comprising several tasks (e.g. table-setting, preparing eggs). After
      forming a detailed plan how to realize these tasks, the sleep group (n = 17)
      spent a night of sleep at home, monitored by polysomnography, and the wake group
      (n = 19) spent a normal day awake, monitored by actigraphy. After a 12-h
      interval, all participants were asked to prepare the virtual breakfast. Contrary
      to our hypothesis, overall performance in breakfast preparation did not differ
      significantly between the sleep and wake groups. However, sleep participants
      performed better in one of six tasks, specifically the 'table-setting' task (P <
      0.01), which was driven by higher scores in a subtask measuring the correct
      position of the tableware (P < 0.01). Additional exploratory analyses revealed
      that a significant number of wake participants performed below the minimal score
      of the sleep group (P < 0.01) and sleep participants achieved the maximal score
      in significantly more subtasks than wake participants (57% versus 27%; P =
      0.018). Plan adherence, assessing how well participants adhered to their own
      previously developed plan, did not differ between the sleep and wake groups.
      These findings provide the first evidence that sleep may support some aspects of
      the realization of complex, somewhat naturalistic plans.

PMID- 29322575
TI  - Vaccine-preventable child deaths in New South Wales from 2005 to 2014: How much
      is preventable?
AB  - AIM: To identify and describe potentially vaccine-preventable child deaths in New
      South Wales (NSW). METHODS: Child deaths in NSW from 2005 to 2014 potentially
      preventable by vaccination were identified from the NSW Child Death Register
      (maintained by the NSW Ombudsman) and the Notifiable Conditions Information
      Management System (NSW Health). Medical and post-mortem records were reviewed.
      Cases were classified as vaccine-preventable based on the strength of evidence
      for the relevant infection causing death and likelihood that death was
      preventable through vaccination. A two-source capture-recapture method was used
      to estimate the true number of deaths. Age-specific mortality rate and number of
      deaths by disease, area of residence and comorbidity were analysed. Deaths were
      classified as preventable based on vaccine availability, eligibility under the
      National Immunisation Program, age and presence of any contraindications.
      RESULTS: Fifty-four deaths were identified as definitely or probably due to
      diseases for which a vaccine was available, with a total average annual mortality
      rate of 0.33 per 100 000 children and 2.1 per 100 000 infants. Two thirds of
      deaths occurred in children with no identified comorbidities. Twenty-three deaths
      were classified as preventable or potentially preventable by vaccination, with
      influenza (12 deaths) and meningococcal disease (five deaths) most common. An
      additional 15 deaths would be potentially preventable as of August 2016 due to
      immunisation recommendation changes including maternal vaccination. CONCLUSION:
      Maternal vaccination along with increased uptake of childhood influenza
      vaccination could reduce child deaths, particularly from influenza.

PMID- 29322576
TI  - A mixed methods thematic review: Health-related decision-making by the older
      person.
AB  - AIMS AND OBJECTIVES: To undertake a mixed methods thematic literature review that
      explored how elderly adults approached decision-making in regard to their health
      care following discharge. BACKGROUND: A critical time for appropriate health
      decisions occurs during hospital discharge planning with nursing staff. However,
      little is known how the 89% of elderly living at home make decisions regarding
      their health care. Research into older adults' management of chronic conditions
      emerges as an important step to potentially encourage symptom monitoring, prevent
      missed care and detect deterioration. All should reduce the risk of hospital re
      admission. DESIGN: A mixed methods thematic literature review was undertaken. The
      structure followed the PRISMA reporting guidelines for systematic reviews
      recommended by the EQUATOR network. METHODS: PubMed, Cumulative Index to Nursing
      and Allied Health Literature (CINAHL) and Scopus online databases were searched
      using keywords, inclusion and exclusion criteria. References drawn from relevant
      publications, identified by experts and published between 1995 and 2017 were also
      considered. Twenty-five qualitative, quantitative and mixed methods studies and
      reviews were critically appraised (CASP 2013) before inclusion in the review.
      Analysis of each study's findings was undertaken using Braun and Clarke's (2006)
      steps to identify major themes and sub-themes. RESULTS: Four main themes
      associated with health-related decision-making in the elderly were identified:
      "the importance of maintaining independence," "decision making style,"
      "management of conditions at home" and "discharge planning." CONCLUSION: Health
      care decision preferences in the elderly emerged as highly complex and influenced
      by multiple factors. Development of a tool to assess these components has been
      recommended. RELEVANCE TO CLINICAL PRACTICE: Nurses play a vital role in
      exploring and understanding the influence that maintaining independence has with
      each patient. This understanding provides an initial step toward development of a
      tool to assist collaboration between patients and healthcare professionals
      involved in their care.

PMID- 29322577
TI  - I just can't please them all and stay sane: Adult child caregivers' experiences
      of family dynamics in care-giving for a parent with dementia in Australia.
AB  - Family caregivers of people with dementia who live within the community often
      experience stress and poor quality of life due to their care-giving role. While
      there are many factors that affect this, one influential factor is the family
      context. This study focussed on adult child caregivers. It examined the specific
      ways that family dynamics contribute to adult child caregivers' distress in the
      context of caring for a parent with dementia. Semi-structured interviews were
      conducted with 17 participants who were adult child primary caregivers for a
      parent with dementia who was living within the community. Interviews were
      audiotaped and transcribed verbatim. Transcripts were analysed using thematic
      analysis. Four themes were identified that represented areas of particular
      concern and distress for the caregivers: family expectations and caregivers' lack
      of choice in adopting the care-giving role; denial and differential
      understandings of dementia among family members; differential beliefs and
      approaches to care-giving among family members; and communication breakdown
      between family members. The findings demonstrate several avenues for further
      research including the development of interventions to support adult child
      caregivers and address problematic family dynamics within the context of caring
      for a parent with dementia.

PMID- 29322578
TI  - The different outcomes of legislative- versus advocacy-led development of
      cannabis policy.

PMID- 29322579
TI  - The employee retention triad in health care: Exploring relationships amongst
      organisational justice, affective commitment and turnover intention.
AB  - AIMS AND OBJECTIVES: To increase understanding of the relationships between
      organisational justice, affective commitment and turnover intention in health
      care. BACKGROUND: Turnover in health care is a serious concern, as it contributes
      to the global nursing shortage and is associated with declines in quality of
      care, patient safety and patient outcomes. Turnover also impacts care teams and
      is associated with decreased staff cohesion and morale. METHODS: A survey was
      developed and administered to frontline nurses working in the Province of
      Ontario, Canada. The data were used to test a hypothetical model developed from a
      review of the literature. The relationships amongst the three constructs were
      evaluated using structural equation modelling and mediation analysis. RESULTS:
      The hypothesised model was generally supported, although we were limited to
      considerations of interpersonal justice, affective commitment to one's
      organisation and turnover intention. Interpersonal justice is associated with
      affective commitment to one's organisation, which is negatively associated with
      turnover intention. Interpersonal justice was also found to be directly and
      negatively associated with turnover intention. Affective commitment to one's
      organisation was also found to mediate the relationship between interpersonal
      justice and turnover intention. CONCLUSIONS: The examination of relationships
      within the "employee retention triad" in a single, comprehensive model is novel
      and provides new information regarding relational complexity and insights into
      what healthcare leaders can do to retain employees. RELEVANCE TO CLINICAL
      PRACTICE: Reducing turnover may help to decrease some of the stressors related to
      turnover for clinical staff remaining at the organisation such as constant
      onboarding and orientation of new hires, working with less experienced staff and
      increased workload due to decreased staffing.

PMID- 29322580
TI  - A study of environmental factors affecting nurses' comfort and protection in
      wearing N95 respirators during bedside procedures.
AB  - AIMS AND OBJECTIVES: To investigate room temperature and relative humidity
      affecting nurses' comfort and protection in wearing N95 respirators during
      clinical bedside procedures. BACKGROUND: N95 respirators are most commonly used
      to protect healthcare workers against airborne diseases. The elastic head straps
      required for tight-fit may cause headache, facial pain and/or ear lobe
      discomfort. Although some past fit test results showed that these respirators are
      likely to fit comfortably, in reality, any discomfort from use may influence
      negatively their appeal and acceptability and thus lower their effectiveness to
      protect the wearers. DESIGN: This study used a comparative study design to
      compare nurses' comfort and protection in wearing N95 respirator during clinical
      nursing procedures. METHOD: The participants (84) were first-year undergraduate
      nursing students from a university in Hong Kong. They were divided randomly into
      four groups (A, B, C and D), with 21 in each group. In this study, they performed
      the Personal Respirator Sampling Test (PRST), a self-developed portable, real
      time fit test method based on the conventional fit test set-up. After this, they
      were asked to complete a usability questionnaire, which was used to record their
      evaluations of the six perceptions of comfort of wearing N95 respirators.
      RESULTS: The participants expressed being comfortable with the respirators at
      warm temperatures of 20 to 24 degrees C. For those participants in Group A who
      had performed fit tests and fit checks, they did not feel hot nor had
      difficulties with breathing. However, they did feel tightness in the respirators
      and experienced discomfort on their ear lobes. CONCLUSION: Room temperature is
      the significant factor affecting the comfort in wearing N95 respirators. It is
      noteworthy that any discomforts from wearing respirators will negatively
      influence their appeal and proper use. Without doubt, comfortable fit makes
      healthcare workers more likely use respirators, hence complying with occupational
      health and safety regulations. RELEVANCE TO CLINICAL PRACTICE: N95 respirator
      wearer's comfort is affected by room temperature. Wearer's comfort can affect
      his/her morale in performing bedside procedures in clinical practice.

PMID- 29322581
TI  - Technical implementations of light sheet microscopy.
AB  - Fluorescence-based microscopy is among the most successful methods in biological
      studies. It played a critical role in the visualization of subcellular structures
      and in the analysis of complex cellular processes, and it is nowadays commonly
      employed in genetic and drug screenings. Among the fluorescence-based microscopy
      techniques, light sheet fluorescence microscopy (LSFM) has shown a quite
      interesting set of benefits. The technique combines the speed of epi-fluorescence
      acquisition with the optical sectioning capability typical of confocal
      microscopes. Its unique configuration allows the excitation of only a thin plane
      of the sample, thus fast, high resolution imaging deep inside tissues is nowadays
      achievable. The low peak intensity with which the sample is illuminated
      diminishes phototoxic effects and decreases photobleaching of fluorophores,
      ensuring data collection for days with minimal adverse consequences on the
      sample. It is no surprise that LSFM applications have raised in just few years
      and the technique has been applied to study a wide variety of samples, from whole
      organism, to tissues, to cell clusters, and single cells. As a consequence, in
      recent years numerous set-ups have been developed, each one optimized for the
      type of sample in use and the requirements of the question at hand. Hereby, we
      aim to review the most advanced LSFM implementations to assist new LSFM users in
      the choice of the LSFM set-up that suits their needs best. We also focus on new
      commercial microscopes and "do-it-yourself" strategies; likewise we review recent
      designs that allow a swift integration of LSFM on existing microscopes.

PMID- 29322582
TI  - Large-scale disturbance legacies and the climate sensitivity of primary Picea
      abies forests.
AB  - Determining the drivers of shifting forest disturbance rates remains a pressing
      global change issue. Large-scale forest dynamics are commonly assumed to be
      climate driven, but appropriately scaled disturbance histories are rarely
      available to assess how disturbance legacies alter subsequent disturbance rates
      and the climate sensitivity of disturbance. We compiled multiple tree ring-based
      disturbance histories from primary Picea abies forest fragments distributed
      throughout five European landscapes spanning the Bohemian Forest and the
      Carpathian Mountains. The regional chronology includes 11,595 tree cores, with
      ring dates spanning the years 1750-2000, collected from 560 inventory plots in 37
      stands distributed across a 1,000 km geographic gradient, amounting to the
      largest disturbance chronology yet constructed in Europe. Decadal disturbance
      rates varied significantly through time and declined after 1920, resulting in
      widespread increases in canopy tree age. Approximately 75% of current canopy area
      recruited prior to 1900. Long-term disturbance patterns were compared to an
      historical drought reconstruction, and further linked to spatial variation in
      stand structure and contemporary disturbance patterns derived from LANDSAT
      imagery. Historically, decadal Palmer drought severity index minima corresponded
      to higher rates of canopy removal. The severity of contemporary disturbances
      increased with each stand's estimated time since last major disturbance,
      increased with mean diameter, and declined with increasing within-stand
      structural variability. Reconstructed spatial patterns suggest that high small
      scale structural variability has historically acted to reduce large-scale
      susceptibility and climate sensitivity of disturbance. Reduced disturbance rates
      since 1920, a potential legacy of high 19th century disturbance rates, have
      contributed to a recent region-wide increase in disturbance susceptibility.
      Increasingly common high-severity disturbances throughout primary Picea forests
      of Central Europe should be reinterpreted in light of both legacy effects
      (resulting in increased susceptibility) and climate change (resulting in
      increased exposure to extreme events).

PMID- 29322583
TI  - Motor imagery training: Kinesthetic imagery strategy and inferior parietal fMRI
      activation.
AB  - Motor imagery (MI) is the mental simulation of action frequently used by
      professionals in different fields. However, with respect to performance, well
      controlled functional imaging studies on MI training are sparse. We investigated
      changes in fMRI representation going along with performance changes of a finger
      sequence (error and velocity) after MI training in 48 healthy young volunteers.
      Before training, we tested the vividness of kinesthetic and visual imagery.
      During tests, participants were instructed to move or to imagine moving the
      fingers of the right hand in a specific order. During MI training, participants
      repeatedly imagined the sequence for 15 min. Imaging analysis was performed using
      a full-factorial design to assess brain changes due to imagery training. We also
      used regression analyses to identify those who profited from training
      (performance outcome and gain) with initial imagery scores (vividness) and fMRI
      activation magnitude during MI at pre-test (MIpre ). After training, error rate
      decreased and velocity increased. We combined both parameters into a common
      performance index. FMRI activation in the left inferior parietal lobe (IPL) was
      associated with MI and increased over time. In addition, fMRI activation in the
      right IPL during MIpre was associated with high initial kinesthetic vividness.
      High kinesthetic imagery vividness predicted a high performance after training.
      In contrast, occipital activation, associated with visual imagery strategies,
      showed a negative predictive value for performance. Our data echo the importance
      of high kinesthetic vividness for MI training outcome and consider IPL as a key
      area during MI and through MI training.

PMID- 29322584
TI  - Effects of fixation on electrophysiology and structure of human jejunal villi.
AB  - The villi of human jejunum vary in size and shape during different functional
      conditions. In the base the lamina propria is isotonic with blood, in the tip
      hyperosmotic. Here we study electrophysiological and morphological effects of
      incubation in hypotonic, isotonic, or hypertonic solutions, and to test various
      isotonic fixatives for microscopy. Samples of jejunal mucosae, obtained during
      surgery in obese patients, were studied in Ussing chambers where electrical
      parameters were registered during incubation in Krebs solution at various
      osmolarities, and during fixation in formaldehyde, glutaraldehyde, or osmium
      tetroxide (OsO4 ). The same fixatives were used for other jejunal specimens that
      were fixed directly for light microscopy. Morphometry was carried out to
      determine size and height of villi, proportion of lamina propria, and surface
      enlargement due to villi. Ussing chamber incubation in fluids with low osmolarity
      resulted in increased electrical resistance and epithelial swelling. Opposite
      results were obtained at high osmolality. Fixation was faster in formaldehyde
      than in glutaraldehyde or OsO4 . In biopsies processed directly for light
      microscopy the proportions of lamina propria of the mucosa, and of lamina propria
      of villi, were significantly larger in biopsies fixed in formaldehyde than after
      fixation in glutaraldehyde or OsO4 . The villus tips sometimes ended with a bleb
      with prominent spaces between the epithelial cells. In summary, jejunal villi
      swell in vitro when exposed to hypotonic solutions, and shrink in hypertonic
      solutions. Much of the morphological changes occurring during fixation can be
      related to the physiological hyperosmolar milieu in villus tips.

PMID- 29322585
TI  - Scapular Fractures in the Pan-scan Era.
AB  - BACKGROUND: Scapular fractures have been traditionally taught to be associated
      with significant injuries and major morbidity. As we demonstrated with sternal
      fracture, pulmonary contusion, and rib fracture, increased chest computed
      tomography (CT) utilization and head-to-pelvis CT (pan-scan) protocols in blunt
      trauma evaluation, however, may diagnose minor, clinically irrelevant scapular
      fractures, possibly rendering previous teachings obsolete. OBJECTIVES: The
      objectives were to determine the 1) percentages of scapular fractures seen on
      chest CT only (SOCTO) versus seen on both chest x-ray (CXR) and CT and of
      isolated scapular fracture (scapular fracture without other thoracic injuries);
      2) frequencies of associated thoracic injury with scapular fracture; and 3)
      proportion of patients admitted, mortality, hospital length of stay, and injury
      severity scores (ISS), comparing four patient groups: scapular fracture,
      nonscapular fracture, scapular fracture SOCTO, and isolated scapular fracture.
      METHODS: We conducted a preplanned analysis of patients prospectively enrolled in
      the NEXUS Chest CT study at nine Level I trauma centers with the following
      inclusion criteria: age > 14 years, blunt trauma within 6 hours of ED
      presentation, and receiving chest imaging during ED trauma evaluation. RESULTS:
      Of 11,477 subjects, 4,501 (39.2%) patients who had both CXR and chest CT and 2.7%
      of these had scapular fractures; 60.3% of these were SOCTO and 23 (19.0%) were
      isolated scapular fracture. The most commonly associated thoracic injuries were
      rib fracture, pulmonary contusion, pneumothorax, and thoracic spine fracture and
      all injuries were more common in scapular fracture patients than nonscapular
      fracture patients. Although scapular fracture patients had higher admission rates
      (86.8% vs. 47.4%; difference in proportions = 39.4% [95% confidence interval {CI}
      = 32.8% to 44.1%]), ISS (21 vs. 5), and length of stay (9.2 days vs. 5.6 days;
      mean difference = 3.4 days [95% CI = 2.1 to 4.7 days]) than patients without
      scapular fracture, their hospital mortality was not significantly different (5.6%
      vs. 3.0%; difference in proportions = 2.6% [95% CI = -8.2% to 0.3%]; unadjusted
      odds ratio = 1.9 [95% CI = 0.9 to 4.2]). Patients with scapular fracture SOCTO
      and isolated scapular fracture had higher admission rates and median ISS than
      nonscapular fracture patients, but their mortality was similar. CONCLUSIONS:
      Under current blunt trauma imaging protocols that commonly include chest CT, most
      scapular fractures are SOCTO and most are associated with other thoracic
      injuries. Although patients with scapular fracture SOCTO and isolated scapular
      fracture have higher admission rates and ISS than nonscapular fracture patients,
      their hospital mortality is similar.

PMID- 29322586
TI  - Functional connectivity predicts gender: Evidence for gender differences in
      resting brain connectivity.
AB  - Prevalence of certain forms of psychopathology, such as autism and depression,
      differs between genders and understanding gender differences of the neurotypical
      brain may provide insights into risk and protective factors. In recent research,
      resting state functional magnetic resonance imaging (rfMRI) is widely used to map
      the inherent functional networks of the brain. Although previous studies have
      reported gender differences in rfMRI, the robustness of gender differences is not
      well characterized. In this study, we use a large data set to test whether rfMRI
      functional connectivity (FC) can be used to predict gender and identify FC
      features that are most predictive of gender. We utilized rfMRI data from 820
      healthy controls from the Human Connectome Project. By applying a predefined
      functional template and partial least squares regression modeling, we achieved a
      gender prediction accuracy of 87% when multi-run rfMRI was used. Permutation
      tests confirmed that gender prediction was reliable ( p<.001). Effects of motion,
      age, handedness, blood pressure, weight, and brain volume on gender prediction
      are discussed. Further, we found that FC features within the default mode (DMN),
      fronto-parietal and sensorimotor networks contributed most to gender prediction.
      In the DMN, right fusiform gyrus and right ventromedial prefrontal cortex were
      important contributors. The above regions have been previously implicated in
      aspects of social functioning and this suggests potential gender differences in
      social cognition mediated by the DMN. Our findings demonstrate that gender can be
      reliably predicted using rfMRI data and highlight the importance of controlling
      for gender in brain imaging studies.

PMID- 29322587
TI  - Growth rings in roots of medicinal perennial dicotyledonous herbs from temperate
      and subtropical zones in China.
AB  - Growth years are closely related to the quality of Chinese medicinal materials,
      and they can provide a reliable basis for quality evaluation on crude drugs in
      accordance with the suitable growth years. Herbchronology, the numerical and
      pattern analysis of annual growth rings in herbaceous perennials, has emerged to
      be a recognized science that is applied in age determination of perennial forbs.
      Fifty medicinal species growing in temperate and subtropical zones of China were
      examined by microstructure observation to determine the presence of growth rings
      in the secondary root xylem of medicinal perennial dicotyledonous herbs. Nearly
      half of the surveyed species showed clearly or relatively clearly demarcated
      growth rings in their roots, and additional anatomical patterns have been
      observed in different species. Clear variations in growth rings of different
      genus or species were characterized in this study, and these findings proved the
      feasibility of applying herbaceous plant growth rings in age identification of
      traditional Chinese medicine.

PMID- 29322588
TI  - Two-frequency CARS imaging by switching fiber laser excitation.
AB  - To fully exploit the power of coherent Raman imaging, techniques are needed to
      image more than one vibrational frequency simultaneously. We describe a method
      for switching between two vibrational frequencies based on a single fiber-laser
      source. Stokes pulses were generated by soliton self-frequency shifting in a
      photonic crystal fiber. Pump and Stokes pulses were stretched to enhance
      vibrational resolution by spectral focusing. Stokes pulses were switched between
      two wavelengths on the millisecond time scale by a liquid-crystal retarder. Proof
      of-principle is demonstrated by coherent anti-Stokes Raman imaging of polystyrene
      beads embedded in a poly(methyl methacrylate) (PMMA) matrix. The Stokes shift was
      switched between 3,050 cm-1 , where polystyrene has a Raman transition, and 2,950
      cm-1 , where both polystyrene and PMMA have Raman resonances. The method can be
      extended to multiple vibrational modes.

PMID- 29322589
TI  - The Direct Cytotoxic Effects of Different Hemostatic Agents on Human Gingival
      Fibroblasts.
AB  - PURPOSE: To evaluate the cytotoxic effects of different hemostatic agents
      (including Expasyl) on human gingival fibroblasts (HGFs) in vitro. MATERIALS AND
      METHODS: HGFs were cultured and exposed to either no medicament treatment or
      1:200 dilution of six different hemostatic agents (Hemox-A, Hemodent,
      Astringedent, Vicostat, Expasyl, 3M ESPE) for 2, 5, 10 minutes, 1 hour, and 24
      hours. Toxicity to HGFs was determined by lactate dehydrogenase activity (LDH)
      and colorimetric (WST-1) assays. Two-tailed t-test was used for statistical
      analyses with alpha level set at 0.05. RESULTS: The group-by-time interactions
      were significant for the LDH and WST-1 assays (p < 0.001). Evaluation of the
      cytotoxic effect of different hemostatic agents at different incubation time
      intervals on the cell membrane damage revealed that Astringedent showed the
      highest cytotoxic effect on HGFs compared to other agents with regards to
      untreated negative control cells at all incubation time intervals (p < 0.001). On
      the other hand, Expasyl showed the least cytotoxic effect with significant
      differences at 5 minutes and 1 hour (p < 0.001) in comparison to other agents.
      CONCLUSIONS: LDH and WST-1 assays of hemostatic agents showed significant
      cytotoxic effect on HGFs at different time intervals. The data suggest that the
      risk for permanent tissue damage might be less significant when Expasyl is used
      during final impression procedure compared to when Astringedent is used.

PMID- 29322590
TI  - Cocoa agroforestry is less resilient to suboptimal and extreme climate than cocoa
      in full sun: Reply to Norgrove (2017).
AB  - Resilience of cocoa agroforestry vs. full sun under extreme climatic conditions.
      In the specific case of our study, the two shade tree species associated with
      cocoa resulted in strong competition for water and became a disadvantage to the
      cocoa plants contrary to expected positive effects.

PMID- 29322591
TI  - Inter-rater agreement of novel high-resolution impedance manometry metrics: Bolus
      flow time and esophageal impedance integral ratio.
AB  - BACKGROUND: Novel high-resolution impedance manometry (HRIM) metrics of bolus
      flow time (BFT) and esophageal impedance integral (EII) ratio have demonstrated
      clinical utility, though the reliability of their analysis has not been assessed.
      We aimed to evaluate the inter-rater agreement of the BFT and EII ratio. METHODS:
      HRIM studies including five upright, liquid swallows from 40 adult patients were
      analyzed by two raters using a customized MATLAB program to generate the BFT and
      EII ratio. Inter-rater agreement was assessed using the intraclass correlation
      coefficient (ICC) for median values generated per patient and also for all 200
      swallows. KEY RESULTS: The ICC (95% confidence interval, CI) for BFT was 0.873
      (0.759-0.933) for median values and 0.838 (0.778-0.881) for all swallows. The ICC
      (95% CI) for EII ratio was 0.983 (0.968-0.991) for median values and 0.905 (0.875
      0.928) for all swallows. Median values for both BFT and EII ratio were similar
      between the two raters (P-values .05). CONCLUSIONS AND INFERENCES: The BFT and
      EII ratio can be reliably calculated as supported by generally excellent inter
      rater agreement. Thus, broader utilization of these measures appears feasible and
      would facilitate further evaluation of their clinical utility.

PMID- 29322592
TI  - Predicting the intrauterine fetal death of fetuses with cystic hygroma in early
      pregnancy.
AB  - We investigated whether it was possible to predict the prognosis of fetuses with
      cystic hygroma in early pregnancy based on the degree of neck thickening. We
      retrospectively analyzed 57 singleton pregnancies with fetuses with cystic
      hygroma who were examined before the 22nd week of pregnancy. The fetuses were
      categorized according to the outcome, structural abnormalities at birth, and
      chromosomal abnormalities. Here, we proposed a new sonographic predictor with
      which we assessed neck thickening by dividing the width of the neck thickening by
      the biparietal diameter, which is expressed as the cystic hygroma
      width/biparietal diameter ratio. The median cystic hygroma width/biparietal
      diameter ratio in the intrauterine fetal death group (0.51) was significantly
      higher than that in the live birth group (0.27). No significant difference in the
      median cystic hygroma width/biparietal diameter ratio was found between the
      structural abnormalities group at birth and the no structural abnormalities
      group, and no significant difference in the median cystic hygroma
      width/biparietal diameter ratio was found between the chromosomal abnormality
      group and the no chromosomal abnormality group. We used receiver operating
      characteristic analysis to evaluate the cystic hygroma width/biparietal diameter
      ratio to predict intrauterine fetal death. When the cystic hygroma
      width/biparietal diameter ratio cut-off value was 0.5, intrauterine fetal death
      could be predicted with a sensitivity of 52.9% and a specificity of 100%. It is
      possible to predict intrauterine fetal death in fetuses with cystic hygroma in
      early pregnancy if cystic hygroma width/biparietal diameter ratio is measured.
      However, even if cystic hygroma width/biparietal diameter ratio is measured,
      predicting the presence or absence of a structural abnormality at birth or a
      chromosomal abnormality is difficult.

PMID- 29322593
TI  - A Simplified Approach to Fabricate a Hollow Ocular Prosthesis.
AB  - The prosthetic rehabilitation of a large anophthalmic socket is always a
      challenge. It demands an equally sized ocular prosthesis to replace lost tissue
      volume. A conventional solid acrylic ocular prosthesis may be deterrent to
      retention and esthetics because of its weight, which can be reduced by
      eliminating the mass of material within it. This article attempts to present a
      simplified and accurate technique to fabricate a hollow ocular prosthesis using
      silicone putty cavity form. It is removed prior to final processing and serves to
      ensure appropriate uniform thickness of acrylic resin and optimal weight
      reduction of the definitive prosthesis without compromising mobility, esthetics,
      and structural integrity.

PMID- 29322594
TI  - Rasagiline improves polysomnographic sleep parameters in patients with
      Parkinson's disease: a double-blind, baseline-controlled trial.
AB  - BACKGROUND AND PURPOSE: The aim was to study the effects of rasagiline on sleep
      quality in patients with Parkinson's disease (PD) with sleep disturbances. Sleep
      disorders are common in PD. Rasagiline is widely used in patients with PD, but
      double-blind polysomnographic trials on its effects on sleep disturbances are
      missing. METHODS: This was a single-center, double-blind, baseline-controlled
      investigator-initiated clinical trial of rasagiline (1 mg/day) over 8 weeks in
      patients with PD with sleep disturbances. Blinding was achieved by running a
      strategic matched placebo parallel group. Co-primary outcome measures were the
      changes between baseline and end of the treatment period in sleep
      maintenance/efficiency as assessed by polysomnography and the Parkinson's Disease
      Sleep Scale Version 2 (PDSS-2) score. RESULTS: A total of 20 of 30 patients were
      randomized to rasagiline (mean +/- SD age, 69.9 +/- 6.9 years; 10 male; Hoehn
      Yahr stage, 1.9 +/- 0.8). Compared with baseline, sleep maintenance was
      significantly increased at the end of the treatment period (relative change
      normalized to baseline, +16.3 +/- 27.9%; P = 0.024, paired two-sided t-test) and
      a positive trend for sleep efficiency was detected (+12.1 +/- 28.6%; P = 0.097).
      Treatment with rasagiline led to significantly decreased wake time after sleep
      onset, number of arousals, percentage of light sleep and improved daytime
      sleepiness as measured by the Epworth Sleepiness Scale. We did not observe
      changes in the co-primary endpoint PDSS-2 score, and no correlations of
      polysomnographic sleep parameters or PDSS-2 score with motor function (Unified
      Parkinson's Disease Rating Scale motor score). Rasagiline was well tolerated with
      no unexpected adverse events. CONCLUSIONS: In patients with PD with sleep
      disturbances, rasagiline showed beneficial effects on sleep quality as measured
      by polysomnography. These effects were probably not related to motor improvement
      or translated into improved overall sleep quality perception by patients.

PMID- 29322595
TI  - Identification of new alpha-synuclein regulator by nontraditional drug
      development pipeline.

PMID- 29322596
TI  - Subclinical depressive symptoms during late midlife and structural brain
      alterations: A longitudinal study of Danish men born in 1953.
AB  - We explored whether depressive symptoms measured three times during midlife were
      associated with structural brain alterations quantified using magnetic resonance
      imaging measurements of volume, cortical thickness, and intensity texture. In 192
      men born in 1953 with depressive symptoms measured at age 51, 56, and 59 years,
      magnetic resonance imaging was performed at age 59. All data processing was
      performed using the Freesurfer software package except for the texture-scores
      that were computed using in-house software. Structural brain alterations and
      associations between depressive symptoms and brain structure outcomes were tested
      using Pearson's correlation, t test, and linear regression. Depressive symptoms
      at age 51 showed clear inverse correlations with total gray matter, pallidum, and
      hippocampal volume with the strongest estimate for hippocampal volume (r = -.22,
      p < .01). After exclusion of men (n = 3) with scores in the range of clinical
      depression the inverse correlation between depressive symptoms and hippocampal
      volume became insignificant (r = -13, p = .08). Depressive symptoms at age 59
      correlated positively with hippocampal and amygdala texture-potential early
      markers of atrophy. Inverse relations with total gray matter and pallidum volumes
      lost significance when the analysis was adjusted for intracranial volume. In men,
      depressive symptoms at age 51 were associated with a reduced volume of the
      hippocampus at age 59 independent of later symptoms. Amygdala and hippocampal
      textures might be the early markers for brain alterations associated with
      depression in midlife.

PMID- 29322597
TI  - The implementation of a successful medication safety program in a primary care.
AB  - RATIONALE, AIMS, AND OBJECTIVES: Improving patient safety is now a government
      priority in many economically developed and underdeveloped countries. Various
      medication safety interventions and programs that have been described in the
      literature focus on hospital settings, and only very few studies report on the
      implementation of such interventions in primary care. The main objectives of this
      study were firstly to describe the steps involved for the successful
      implementation of a medication safety program in primary care in rural Australia
      and secondly to report on its evaluation and provide recommendations for future
      initiatives. METHOD: The implementation of the medication safety program within
      the study organization included several steps, and these were as follows:
      collection of baseline medications incidents within the organization over the
      last 2 years, delivery of a medication safety training to clinicians working
      within the organization, formation of a medication safety group, and
      implementation of the newly developed medication safety guidelines within the
      organization. Clinicians' knowledge, behaviour, confidence, and satisfaction were
      also collected before and after the implementation. RESULTS: The results show
      that medication safety training has improved clinicians' knowledge, confidence,
      behaviour, and utilization positively. There was a significant increase in the
      clinicians' confidence and satisfaction in applying the training to their daily
      practice (P value of 0.02). The implementation of the medication safety program
      across the study organization sites relied on 3 main stages. These were connect
      and communicate, collaboration, and consolidation. In the first stage of the
      project, we focused on identifying the key issues contributing to medication
      errors across the organization using an evidence-based approach to identify the
      types of medications errors. CONCLUSION: The success of the implementation of a
      collaborative medication safety program within a large organization is dependent
      on emphasizing a wide culture of patient safety and understanding the medication
      incident reports within an organization.

PMID- 29322598
TI  - Erythritol production by yeasts: a snapshot of current knowledge.
AB  - Erythritol is a four-carbon sugar alcohol produced by microorganisms as an
      osmoprotectant. It could be used as a natural sweetener in the pharmaceutical and
      food industries. Here, a snapshot of current knowledge on erythritol metabolism
      and synthesis, optimization of its production and more precise process and
      producer strain improvement is presented.

PMID- 29322599
TI  - Non-invasive evaluation of portal hypertension using shear-wave elastography:
      analysis of two algorithms combining liver and spleen stiffness in 191 patients
      with cirrhosis.
AB  - BACKGROUND: Two algorithms based on sequential measurements of liver and spleen
      stiffness using two-dimensional shearwave elastography (2D-SWE) have been
      recently proposed to estimate clinically significant portal hypertension (hepatic
      venous pressure gradient [HVPG] >=10 mm Hg) in patients with cirrhosis, with
      excellent diagnostic accuracy. AIM: To validate externally these algorithms in a
      large cohort of patients with cirrhosis. METHODS: One hundred and ninety-one
      patients with stable cirrhosis (Child-Pugh class A 39%, B 29% and C 31%) who
      underwent liver and spleen stiffness measurements using 2D-SWE at the time of
      HVPG measurement were included. Diagnostic accuracy of the 2 algorithms was
      assessed by calculating sensitivity, specificity, positive and negative
      predictive values. RESULTS: The first algorithm, using liver stiffness <16.0
      kilopascals (kPa) and then spleen stiffness <26.6 kPa, was used to rule-out HVPG
      >=10 mm Hg. In our population, its sensitivity and negative predictive value were
      95% and 63% respectively. The second algorithm, using liver stiffness >38.0 kPa,
      or liver stiffness <=38.0 kPa but spleen stiffness >27.9 kPa, was used to rule-in
      HVPG >=10 mm Hg. In our population, its specificity and positive predictive value
      were 52% and 83% respectively. Restricting the analyses to the 74 patients
      without any history of decompensation of cirrhosis or to the 65 patients with
      highly reliable liver stiffness measurement did not improve the results.
      CONCLUSION: In our population, diagnostic accuracies of non-invasive algorithms
      based on sequential measurements of liver and spleen stiffness using 2D-SWE were
      acceptable, but not good enough to replace HVPG measurement or to base clinical
      decisions.

PMID- 29322600
TI  - Using Enamel Matrix Derivative to Improve Treatment Efficacy in Periodontal
      Furcation Defects.
AB  - PURPOSE: Furcations are complicated periodontal defects. Untreated furcations
      lead to loss of the involved teeth and supporting tissues. It has been
      demonstrated that regenerative biomaterials are beneficial in reconstruction of
      the bone surrounding furcation-affected teeth. These biomaterials range from bone
      grafts and nonresorbable/resorbable barrier membranes to biologics that are able
      to trigger inactive regenerative processes in periodontal tissues. Selection of
      appropriate material(s) to treat furcations is challenging. The aim of this
      article is to provide a comparative outlook on different biomaterials applicable
      in regeneration of furcations with a focus on enamel matrix derivative (EMD).
      METHODS: Scientific databases including PubMed/MEDLINE, ScienceDirect, and EMBASE
      were searched, and 28 articles were found primarily for this specific study. Full
      texts were studied to identify relevant studies; 17 studies were excluded because
      of irrelevancy, while 11 main studies were ultimately selected. Other references
      have been used for general statements. RESULTS: EMD is a protein complex widely
      used in the regeneration of different periodontal defects. To assess the effects
      of EMD for treatment of root furcations, clinical studies involving EMD with and
      without barrier membranes and bone grafts were selected and compared. Briefly,
      this study reveals that when EMD is combined with open flap debridement (OFD),
      guided tissue regeneration (GTR), or bone grafting (BG), the amount of class II
      furcations converted to class I increases significantly. EMD also reduces tissue
      swelling and patient discomfort after treatment. CONCLUSIONS: This study provides
      evidence to find the best combination of biomaterials to treat furcation defects.
      The best results are obtained if EMD is combined with beta-TCP/HA alloplastic
      bone grafts.

PMID- 29322601
TI  - Temperature sensitivities of extracellular enzyme Vmax and Km across thermal
      environments.
AB  - The magnitude and direction of carbon cycle feedbacks under climate warming
      remain uncertain due to insufficient knowledge about the temperature
      sensitivities of soil microbial processes. Enzymatic rates could increase at
      higher temperatures, but this response could change over time if soil microbes
      adapt to warming. We used the Arrhenius relationship, biochemical transition
      state theory, and thermal physiology theory to predict the responses of
      extracellular enzyme Vmax and Km to temperature. Based on these concepts, we
      hypothesized that Vmax and Km would correlate positively with each other and show
      positive temperature sensitivities. For enzymes from warmer environments, we
      expected to find lower Vmax , Km , and Km temperature sensitivity but higher Vmax
      temperature sensitivity. We tested these hypotheses with isolates of the
      filamentous fungus Neurospora discreta collected from around the globe and with
      decomposing leaf litter from a warming experiment in Alaskan boreal forest. For
      Neurospora extracellular enzymes, Vmax Q10 ranged from 1.48 to 2.25, and Km Q10
      ranged from 0.71 to 2.80. In agreement with theory, Vmax and Km were positively
      correlated for some enzymes, and Vmax declined under experimental warming in
      Alaskan litter. However, the temperature sensitivities of Vmax and Km did not
      vary as expected with warming. We also found no relationship between temperature
      sensitivity of Vmax or Km and mean annual temperature of the isolation site for
      Neurospora strains. Declining Vmax in the Alaskan warming treatment implies a
      short-term negative feedback to climate change, but the Neurospora results
      suggest that climate-driven changes in plant inputs and soil properties are
      important controls on enzyme kinetics in the long term. Our empirical data on
      enzyme Vmax , Km , and temperature sensitivities should be useful for
      parameterizing existing biogeochemical models, but they reveal a need to develop
      new theory on thermal adaptation mechanisms.

PMID- 29322602
TI  - Outcomes of more than 1 000 percutaneous nephrolithotomies and validation of
      Guy's stone score.
AB  - OBJECTIVE: To present the experience with percutaneous nephrolithotomy (PCNL) at
      a high-volume Brazilian centre and to evaluate Guy's stone score (GSS) as a
      predictor of success and complications in PCNL. PATIENTS AND METHODS: We
      prospectively evaluated patients who underwent PCNL between June 2011 and October
      2016. Indications for PCNL included renal stones >2 cm in size and stones <2 cm
      in size in which first-line techniques had failed. All patients underwent a
      complete preoperative evaluation, including non-contrast-enhanced abdominal
      computed tomography (CT). Stone complexity was assessed using GSS. Success was
      defined as the absence of fragments >2 mm on CT on postoperative day 1.
      Complications were classified according to the Clavien grade. RESULTS: A total of
      1 066 PCNLs were performed on 891 patients. In all, 20.2% were classified as
      GSS1, 27.4% as GSS2, 35.0% as GSS3, and 17.4% as GSS4. The mean operating time
      was 108.44 min, and the mean fluoroscopy time was 13.57 min. The overall
      immediate success rate based on postoperative day 1 CT was 43.8%. Complications
      occurred in 14.9% of cases, and the mean length of hospital stay was 54.55 h.
      Stratifying patients according to GSS, success rate was inversely proportional to
      the calculus complexity: GSS1: 87.9%; GSS2: 62.1%; GSS3: 44.0%; and GSS4: 24.3%
      (P < 0.001). Higher GSS categories were significantly correlated with the number
      of puncture tracts (P < 0.001), operating time (P < 0.001), fluoroscopy time (P <
      0.001), blood transfusion rate (P < 0.001), complications (P < 0.001) and length
      of stay (P < 0.001). CONCLUSION: In a high-volume centre, PCNL was a reliable
      surgical technique, with low morbidity and short hospital stay. GSS was confirmed
      to be a very useful tool for predicting the outcomes of PCNL, and its use should
      be encouraged.

PMID- 29322603
TI  - The nerve supply of zygomaticus major: Variability and distinguishing zygomatic
      from buccal facial nerve branches.
AB  - The zygomaticus major (ZM) is important for the human smile. There are
      conflicting data about whether the zygomatic or buccal branches of the facial
      nerve are responsible for its motor innervation. The literature provides no
      precise distinction of the transition zone between these two branch systems. In
      this study, a definition to distinguish the facial nerve branches at the level of
      the body of the zygoma is proposed. In the light of this definition, we conducted
      an anatomical study to determine how the source of innervation of the ZM was
      distributed. A total of 96 fresh-frozen cadaveric facial halves were dissected
      under loupe magnification. A hemiparotidectomy was followed by antegrade
      microsurgical dissection. Any branch topographically lying superficial to the
      zygoma or touching it was classed as zygomatic, and any neighboring inferior
      branch was considered buccal. The arborization of the facial nerve was diffuse in
      all cases. In 64 out of 96 specimens (67%, 95% CI: 56% to 76%), zygomatic
      branches innervated the ZM. Buccal branches innervated ZM in the other 32 facial
      halves (33%, 95% CI: 24% to 44%). There were no differences in respect of sex or
      facial side. All facial halves displayed additional branches, which crossed the
      muscle on its inner surface without supplying it. In 31 specimens, a nerve branch
      ran superficial to ZM in its cranial third. According to our classification, the
      zygomaticus major is innervated by zygomatic branches in 67% of cases and by
      buccal branches in 33%. Clin. Anat. 31:560-565, 2018. (c) 2018 Wiley Periodicals,
      Inc.

PMID- 29322604
TI  - Clinical characteristics and outcome in dogs with small cell T-cell intestinal
      lymphoma.
AB  - Small cell intestinal lymphoma has not been well characterized in dogs. The
      objective of this study was to describe clinical characteristics and outcome in
      dogs with small cell intestinal lymphoma. We hypothesized that affected dogs
      would have prolonged survival compared with high-grade gastrointestinal (GI)
      lymphoma. Pathology records were searched for dogs with histologically confirmed
      small cell GI lymphoma. Seventeen dogs with confirmed small cell intestinal
      lymphoma were identified, and clinical and outcome data were retrospectively
      collected. Histopathology was reviewed by a board-certified pathologist, and
      tissue sections were subjected to immunophenotyping and molecular clonality
      assessment. All dogs had small cell, T-cell, lymphoma confirmed within various
      regions of small intestine, with 1 dog also having disease in abdominal lymph
      nodes. All dogs had clinical signs attributable to GI disease; diarrhoea (n = 13)
      was most common. Ultrasonographic abnormalities were present in 8 of 13 dogs with
      abnormal wall layering (n = 7) and hyperechoic mucosal striations (n = 7)
      representing the most common findings. In total, 14 dogs received some form of
      treatment. The median survival time (MST) for all dogs was 279 days and the MST
      for the 14 dogs that received any treatment was 628 days. Dogs with anaemia and
      weight loss at presentation had significantly shorter survival times and dogs
      that received a combination of steroids and an alkylating agent had significantly
      longer survival times. Small cell, T-cell, intestinal lymphoma is a distinct
      disease process in dogs, and those undergoing treatment may experience prolonged
      survival.

PMID- 29322605
TI  - DECLARE-TIMI 58: Participants' baseline characteristics.
AB  - AIM: To describe the baseline characteristics of participants randomized in the
      Dapagliflozin Effect on CardiovascuLAR Events (DECLARE-TIMI 58) trial, the
      pivotal study conducted to assess cardiovascular (CV) outcomes with
      dapagliflozin. METHODS: The DECLARE-TIMI 58 trial will analyse 17 160 patients
      with type 2 diabetes randomized to treatment with dapagliflozin (10 mg/d) or
      matching placebo. We analysed their baseline characteristics. RESULTS: The
      participants' mean +/- SD age was 63.8 +/- 6.8 years, 62.6% were male, and their
      mean +/- SD diabetes duration was 11.8 +/- 7.8 years, glycated haemoglobin 8.3%
      +/- 1.2% (67 mmol/mol +/- 9.7 mmol/mol) and body mass index 32.1 +/- 6.0 kg/m2 .
      Randomization included 6971 (40.6%) patients with atherosclerotic CV disease
      (CVD), and 10 189 (59.4%) patients with multiple risk factors (MRF) for CVD
      (defined as men age >= 55 years or women >=60 years, with at least one of
      dyslipidaemia, hypertension or smoking). Patients with CVD compared with patients
      with MRF were younger (62.5 +/- 8.1 vs 64.7 +/- 5.6 years), more frequently male
      (72.1% vs 56.1%), less often used metformin (74.6% vs 81.2%), more often used
      insulin (44.2% vs 36.4%), and more frequently used statins, aspirin, clopidogrel
      and beta-blockers (82.2%, 71.1%, 24.7% and 66.6% vs 63.7%, 39.1%, 1.5% and 32.3%,
      respectively). CONCLUSION: The DECLARE-TIMI 58 trial is expected to provide
      conclusive data on the effect of treatment with dapagliflozin in addition to
      standard of care, on CV outcomes in a broad patient population with type 2
      diabetes and CVD or MRF for CVD.

PMID- 29322606
TI  - Association of tumour-infiltrating regulatory T cells with adverse outcomes in
      dogs with malignant tumours.
AB  - Regulatory T cells (Tregs) infiltrate into a variety of tumour tissues and
      associate with poor prognosis in humans. However, data on association of Treg
      infiltration with prognosis is limited in canine tumours. The purpose of this
      study was to examine the number of tumour-infiltrating Tregs and its association
      with overall survival (OS) in dogs with malignant tumours. The following 168
      canine tumours were included: 37 oral malignant melanomas (OMMs); 14 oral
      squamous cell carcinomas (OSCCs); 16 pulmonary adenocarcinomas (PAs); 37 mammary
      carcinomas (MCs); 36 mast cell tumours (MCTs) and 28 hepatocellular carcinomas
      (HCCs). Normal tissues were obtained from 8 healthy dogs as controls. The number
      of forkhead box P3 (Foxp3)-positive Tregs in intratumoral and peritumoral areas
      was investigated by immunohistochemistry. OS was compared between high and low
      Treg groups. The number of intratumoral and peritumoral Foxp3-positive Tregs was
      significantly higher in OMM, OSCC, PA and MC compared with each normal tissue.
      There were few Foxp3-positive Tregs in MCT and HCC. With intratumoral Tregs, the
      OS in the high Treg group was significantly shorter than that in the low Treg
      group in OMM, OSCC and PA. With peritumoral Tregs, there was no significant
      difference for OS between the 2 groups in each tumour type. These results suggest
      that Tregs infiltrate into a variety of canine tumours and the abundance of Tregs
      are associated with poor prognosis in some solid tumour types.

PMID- 29322607
TI  - Stenting of the inter-atrial septum in infants and small children: Indications,
      techniques and outcomes.
AB  - OBJECTIVES: To evaluate the procedural success and outcome of inter-atrial
      stenting. BACKGROUND: Inter-atrial stenting has been shown to be an effective way
      to maintain inter-atrial blood flow, however it is considered a high risk
      procedure, usually performed urgently in patients with significant hemodynamic
      compromise. METHODS: Between September 2004 and August 2016, inter-atrial
      stenting was attempted in 29 children. Procedural, clinical, and follow-up data
      were collected retrospectively. RESULTS: The procedures were completed
      successfully in 27 patients. Twenty-five procedures were undertaken
      percutaneously, with the remaining four being performed as hybrid procedures. The
      patients were considered as high risk for adverse events (82% scored as CRISP 4
      and 5) with four deaths during the first 24 hr (14%). Procedural complications
      occurred in eight patients (28%) with related death in three patients (10%). One
      further patient died after an uncomplicated technically successful stent
      implantation performed as a salvage procedure. Procedural complications (71% vs.
      14%) and mortality (43% vs. 5%) were higher in those, who weighed 3 kg or less (P
      < 0.05). Patency of the stents was maintained until planned staged surgery in 22
      patients at a mean of 302 days. Three patients underwent further balloon dilation
      for flow restriction at 58-201 days. In two un-operated patients the stents
      remained patent at follow-up. One patient with severe pulmonary hypertension died
      with a patent stent. CONCLUSIONS: Inter-atrial stenting produces reliable patency
      with a very good success rate. Morbidity and mortality were related to low weight
      at the time of the procedure.

PMID- 29322609
TI  - Peer teaching and information retrieval: the role of the NICE Evidence search
      student champion scheme in enhancing students' confidence.
AB  - BACKGROUND: This research reports on the NICE Evidence search (ES) student
      champion scheme (SCS) first five years of activity (2011-2016) in terms of its
      impact on health care undergraduate students' information search skills and
      search confidence. OBJECTIVES: A review of students' evaluation of the scheme was
      carried out to chart the changes in attitude towards NICE Evidence search as an
      online health care information source and to monitor students' approach to
      information seeking. METHODS: This study is based on the results of
      questionnaires distributed to students before and after attending a training
      session on NICE Evidence search delivered by their own peers. The exercise was
      implemented in health related universities in England over a period of five
      consecutive academic years. RESULTS: (i) Students' search confidence improved
      considerably after the training; (ii) ES was perceived as being an increasingly
      useful resource of evidence based information for their studies; (iii) the
      training helped students develop discerning search skills and use evidence based
      information sources more consistently and critically. CONCLUSIONS: The NICE SCS
      improves confidence in approaching information tasks amongst health care
      undergraduate students. Future developments could involve offering the training
      at the onset of a course of study and adopting online delivery formats to expand
      its geographical reach.

PMID- 29322608
TI  - Comparison of listeriolysin O and phospholipases PlcA and PlcB activities, and
      initial intracellular growth capability among food and clinical strains of
      Listeria monocytogenes.
AB  - AIMS: We investigated whether Listeria monocytogenes strains differ in their
      ability to escape from the primary phagosome after internalization into human
      intestinal epithelial cells. METHODS AND RESULTS: Food and clinical strains were
      used to study specific alleles; the activities of listeriolysin O (LLO) and
      phospholipases PlcA and PlcB, which promote rupture of the phagocytic vacuole;
      and initial intracellular bacterial growth in Caco-2 cells. Results showed no
      difference in LLO activities between food and clinical strains or among
      serotypes. In contrast, the LLO truncation mutant lacked detectable haemolytic
      activity and intracellular growth. PlcA and PlcB produced by the strains of
      serotypes 4b/4e and 1/2b exhibited significantly lower activities than those of
      serotypes 1/2a and 1/2c. In contrast, the strains of serotype 1/2b grew
      significantly faster than those of serotypes 4b/4e and 1/2a. Moreover, the PrfA
      truncation mutants lacked LLO and phospholipases activities and did not show
      intracellular growth. CONCLUSIONS: We determined that LLO and PrfA mutants exert
      a significant effect on intracellular growth, although it was unclear from this
      study whether PlcA and PlcB alleles affect escape from vacuoles. SIGNIFICANCE AND
      IMPACT OF THE STUDY: This study estimates that low-virulence L. monocytogenes
      strains associated with escape ability from the primary vacuoles are not widely
      distributed among food strains.

PMID- 29322610
TI  - Safety and efficacy of once-weekly semaglutide vs additional oral antidiabetic
      drugs in Japanese people with inadequately controlled type 2 diabetes: A
      randomized trial.
AB  - AIM: To evaluate the safety and efficacy of once-weekly subcutaneous semaglutide
      as monotherapy or combined with an oral antidiabetic drug (OAD) vs an additional
      OAD added to background therapy in Japanese people with type 2 diabetes (T2D)
      inadequately controlled on diet/exercise or OAD monotherapy. METHODS: In this
      phase III, open-label trial, adults with T2D were randomized 2:2:1 to semaglutide
      0.5 mg or 1.0 mg, or one additional OAD (a dipeptidyl peptidase-4 inhibitor,
      biguanide, sulphonylurea, glinide, alpha-glucosidase inhibitor or
      thiazolidinedione) with a different mode of action from that of background
      therapy. The primary endpoint was number of adverse events (AEs) after 56 weeks.
      RESULTS: Baseline characteristics were balanced between treatment arms (601
      randomized). More AEs were reported in the semaglutide 0.5 mg (86.2%) and 1.0 mg
      (88.0%) groups than in the additional OAD group (71.7%). These were typically
      mild/moderate. Gastrointestinal AEs were most frequent with semaglutide, which
      diminished over time. The mean glycated haemoglobin (HbA1c) concentration
      (baseline 8.1%) was significantly reduced with semaglutide 0.5 mg and 1.0 mg vs
      additional OAD (1.7% and 2.0% vs 0.7%, respectively; estimated treatment
      difference [ETD] vs additional OAD -1.08% and -1.37%, both P < .0001). Body
      weight (baseline 71.5 kg) was reduced by 1.4 kg and 3.2 kg with semaglutide 0.5
      mg and 1.0 mg, vs a 0.4-kg increase with additional OAD (ETD -1.84 kg and -3.59
      kg; both P < .0001). For semaglutide-treated participants, >80% achieved an HbA1c
      concentration <7.0% (Japanese Diabetes Society target). CONCLUSIONS: Semaglutide
      was well tolerated, with no new safety issues identified. Semaglutide treatment
      significantly reduced HbA1c and body weight vs additional OAD treatment in
      Japanese people with T2D.

PMID- 29322611
TI  - Impact of pre-procedural hyponatremia on clinical outcomes after transcatheter
      aortic valve replacement: A propensity-matched analysis.
AB  - BACKGROUND: Hyponatremia is associated with the increased risk of early and late
      mortality in patients with cardiac disease. This study aimed to assess the
      prognostic value of hyponatremia in patients who had undergone transcatheter
      aortic valve replacement (TAVR). METHODS: We investigated 1,215 consecutive
      patients (mean age: 84.4 +/- 5.0 years) who underwent TAVR using data from the
      Optimized CathEter vAlvular iNtervention (OCEAN)-TAVR Japanese multicenter
      registry. Hyponatremia was defined as a serum sodium value less than 135 mEq/L.
      The baseline characteristics, procedural outcomes, all-cause, cardiovascular, and
      non-cardiovascular mortality were compared between patients with hyponatremia (n
      = 106, 8.7%) and without hyponatremia (n = 1,109, 91.3%). A propensity-matching
      analysis was used to adjust for the non-uniform patient characteristics. RESULTS:
      Differences in the baseline characteristics were observed between the two groups
      regarding the prevalence of pulmonary disease (37.7% vs. 28.9%, P = 0.04) and the
      performance of non-elective TAVR (10.4% vs. 4.2%, P = 0.01), although these were
      minimized in the matched model. The 30-day mortality rates differed between the
      two groups (7.6% vs. 1.4%, P < 0.001). During a mean follow-up of 330 days, the
      all-cause and cardiovascular mid-term mortality were higher in the hyponatremia
      group than in the non-hyponatremia group (log-rank test: P = 0.0047, and P <
      0.001, respectively). The three findings above were not attenuated in the
      propensity-matched model (P < 0.001, P = 0.0044, and P = 0.014, respectively). In
      contrast, there was no difference in non-cardiovascular mortality between the two
      groups in both the overall and matched model (P = 0.40 and P = 0.13,
      respectively). CONCLUSIONS: Pre-procedural hyponatremia may be a useful marker
      for predicting early and mid-term clinical outcomes after TAVR.

PMID- 29322612
TI  - Validation of contemporary risk scores in predicting coronary thrombotic events
      and major bleeding in patients with acute coronary syndrome after drug-eluting
      stent implantations.
AB  - OBJECTIVES: We aimed to assess the prognostic ability of the ST score, DAPT
      score, and PARIS score in a Chinese population. BACKGROUND: Recently, several
      risk scores predicting the long-term risk of coronary thrombotic events [CTE,
      defined as the composite of definite or probable stent thrombosis (ST) and
      myocardial infarction] and bleeding have been developed and initially validated
      in Western populations. METHODS: A total of 6,088 consecutive patients with acute
      coronary syndrome (mean age 58.3 +/- 10.4; women 23.1%) treated with drug-eluting
      stents in 2013 at our single institution were enrolled. We calculated risk scores
      and evaluated their performance for predicting definite or probable ST, CTE and
      major bleeding (MB, defined as the occurrence of a Bleeding Academic Research
      Consortium type 3 or 5 bleed). The prognostic value of risk scores was assessed
      by receiver-operating characteristic curves. RESULTS: The ST score, DAPT score,
      and PARIS score all showed unsatisfactory discrimination to predict 2-year or 1-
      to 2-year ST and CTE (c-statistic = 0.51-0.59). With respect to bleeding
      outcomes, the PARIS score showed unsatisfactory discrimination in predicting 2
      year MB (c-statistic = 0.56); the DAPT score performed slightly better than the
      PARIS score in predicting occurrence of later MB events between 1 and 2 years,
      whereas its discriminative capacity was only modest (c-statistic = 0.71).
      CONCLUSIONS: The current three risk scores, derived and initially validated in
      Western populations, may not be applicable to the Chinese population, although
      DAPT score was determined to be a modestly accurate quantitative tool for
      prediction of later MB.

PMID- 29322613
TI  - Forward view: advancing health library and knowledge services in England.
AB  - This article is the fourth in a series on New Directions. The National Health
      Service is under pressure, challenged to meet the needs of an ageing population,
      whilst striving to improve standards and ensure decision making is underpinned by
      evidence. Health Education England is steering a new course for NHS library and
      knowledge services in England to ensure access to knowledge and evidence for all
      decision makers. Knowledge for Healthcare calls for service transformation, role
      redesign, greater coordination and collaboration. To meet user expectations,
      health libraries must achieve sustainable, affordable access to digital content.
      Traditional tasks will progressively become mechanised. Alongside supporting
      learners, NHS librarians and knowledge specialists will take a greater role as
      knowledge brokers, delivering business critical services. They will support the
      NHS workforce to signpost patients and the public to high-quality information.
      There is a need for greater efficiency and effectiveness through greater co
      operation and service mergers. Evaluation of service quality will focus more on
      outcomes, less on counting. These changes require an agile workforce, fit for the
      future. There is a bright future in which librarians' expertise is used to
      mobilise evidence, manage and share knowledge, support patients, carers and
      families, optimise technology and social media and provide a keystone for
      improved patient care and safety.

PMID- 29322615
TI  - Melatonin protects against Abeta-induced neurotoxicity in primary neurons via miR
      132/PTEN/AKT/FOXO3a pathway.
AB  - Alzheimer's disease (AD) is a kind of neurodegenerative disorder associated with
      age. Investigations suggest that amyliod-beta (Abeta) is implicated in the
      pathogenesis of AD. The accumulation of Abeta in the brain causes oxidative
      stress and synaptic toxicity, leads to synaptic dysfunction and neuronal death.
      Previous investigations suggest that melatonin an endogenous hormone can
      counteract Abeta-induced neurotoxicity. However, the molecular mechanisms of
      Abeta-induced toxicity and melatonin treatment remain elusive. Studies indicate
      that microRNA-132 is crucial for neuronal survival and plays a key role in the
      pathological process of AD. Moreover, PTEN and FOXO3a two key targets of miR-132
      are upregulated in the AD brain. Here, we exposed the primary cultured cortical
      neurons with Abeta25-35 and treated with melatonin. Our investigations
      demonstrated that Abeta25-35 exposure significantly decreased the expression of
      miR-132 and elevated the expression of PTEN and FOXO3a. Whereas, melatonin
      treatment could rescue the expression of miR-132 and downregulate the level of
      PTEN and FOXO3a. Moreover, melatonin blocked the nuclear translocation of FOXO3a
      and thereby suppressed its pro-apoptotic pathways. In addition, our
      investigations suggested that the over-expression of miR-132 could block Abeta
      induced neurotoxicity. We also found that VO-OHpic (PTEN inhibitor) could
      counteract Abeta-induced neuronal damage, and LY294002 (AKT inhibitor) suppressed
      the protective effect of melatonin. Together, these results indicate that
      melatonin exerts its neuroprotective effect in Abeta-induced neurotoxicity via
      miR-132/PTEN/AKT/FOXO3a pathway. (c) 2018 BioFactors, 00(00):000-000, 2018.

PMID- 29322614
TI  - Method for automatic detection of defective ultrasound linear array transducers
      based on uniformity assessment of clinical images - A case study.
AB  - The purpose of the present study was to test an idea of and describe a concept of
      a novel method of detecting defects related to horizontal nonuniformities in
      ultrasound equipment. The method is based on the analysis of ultrasound images
      collected directly from the clinical workflow. In total over 31000 images from
      three ultrasound scanners from two vendors were collected retrospectively from a
      database. An algorithm was developed and applied to the images, 150 at a time,
      for detection of systematic dark regions in the superficial part of the images.
      The result was compared with electrical measurements (FirstCall) of the
      transducers, performed at times when the transducers were known to be defective.
      The algorithm made similar detection of horizontal nonuniformities for images
      acquired at different time points over long periods of time. The results showed
      good subjective visual agreement with the available electrical measurements of
      the defective transducers, indicating a potential use of clinical images for
      early and automatic detection of defective transducers, as a complement to
      quality control.

PMID- 29322617
TI  - PREVIEW (Prevention of Diabetes Through Lifestyle Intervention and Population
      Studies in Europe and Around the World) study in children aged 10 to 17 years:
      Design, methods and baseline results.
AB  - Insulin resistance (IR) in adolescence is associated with type 2 diabetes
      mellitus [T2DM]. The PREVIEW (Prevention of Diabetes Through Lifestyle
      Intervention and Population Studies in Europe and Around the World) study
      assessed the effectiveness of a high-protein, low-glycaemic-index diet and a
      moderate-protein, moderate-glycaemic-index diet to decrease IR in insulin
      resistant children who were overweight or obese. Inclusion criteria were age 10
      to 17 years, homeostatic model assessment of IR (HOMA-IR) >=2.0 and
      overweight/obesity. In 126 children (mean +/- SD age 13.6 +/- 2.2 years, body
      mass index [BMI] z-score 3.04 +/- 0.66, HOMA-IR 3.48 +/- 2.28) anthropometrics,
      fat mass percentage (FM%), metabolic characteristics, physical activity, food
      intake and sleep were measured. Baseline characteristics did not differ between
      the groups. IR was higher in pubertal children with morbid obesity than in
      prepubertal children with morbid obesity (5.41 +/- 1.86 vs 3.23 +/- 1.86; P =
      .007) and prepubertal and pubertal children with overweight/obesity (vs 3.61 +/-
      1.60, P = .004, and vs 3.40 +/- 1.50, P < .001, respectively). IR was associated
      with sex, Tanner stage, BMI z-score and FM%. Fasting glucose concentrations were
      negatively associated with Baecke sport score (r = -0.223, P = .025) and
      positively with daytime sleepiness (r = 0.280, P = .016) independent of sex,
      Tanner stage, BMI z-score and FM%. In conclusion, IR was most severe in pubertal
      children with morbid obesity. The associations between fasting glucose
      concentration and Baecke sport score and sleepiness suggest these might be
      possible targets for diabetes prevention.

PMID- 29322616
TI  - Development of methods and feasibility of using hyperpolarized carbon-13 imaging
      data for evaluating brain metabolism in patient studies.
AB  - PURPOSE: Hyperpolarized carbon-13 (13 C) metabolic imaging is a noninvasive
      imaging modality for evaluating real-time metabolism. The purpose of this study
      was to develop and implement experimental strategies for using [1-13 C]pyruvate
      to probe in vivo metabolism for patients with brain tumors and other neurological
      diseases. METHODS: The 13 C radiofrequency coils and pulse sequences were tested
      in a phantom and were performed using a 3 Tesla whole-body scanner. Samples of [1
      13 C]pyruvate were polarized using a SPINlab system. Dynamic 13 C data were
      acquired from 8 patients previously diagnosed with brain tumors, who had received
      treatment and were being followed with serial magnetic resonance scans. RESULTS:
      The phantom studies produced good-quality spectra with a reduction in signal
      intensity in the center attributed to the reception profiles of the 13 C receive
      coils. Dynamic data obtained from a 3-cm slice through a patient's brain
      following injection with [1-13 C]pyruvate showed the anticipated arrival of the
      agent, its conversion to lactate and bicarbonate, and subsequent reduction in
      signal intensity. A similar temporal pattern was observed in 2D dynamic patient
      studies, with signals corresponding to pyruvate, lactate, and bicarbonate being
      in normal appearing brain, but only pyruvate and lactate being detected in
      regions corresponding to the anatomical lesion. Physiological monitoring and
      follow-up confirmed that there were no adverse events associated with the
      injection. CONCLUSION: This study has presented the first application of
      hyperpolarized 13 C metabolic imaging in patients with brain tumor and
      demonstrated the safety and feasibility of using hyperpolarized [1-13 C]pyruvate
      to evaluate in vivo brain metabolism. Magn Reson Med 80:864-873, 2018. (c) 2018
      International Society for Magnetic Resonance in Medicine.

PMID- 29322618
TI  - Genome-enabled metabolic reconstruction of dominant chemosynthetic colonizers in
      deep-sea massive sulfide deposits.
AB  - Deep-sea massive sulfide deposits remaining after ceasing of hydrothermal
      activity potentially provide energy for a chemosynthetic ecosystem in the dark,
      cold marine environments. Although yet-uncultivated bacteria in the phylum
      Nitrospirae and the class Deltaproteobacteria are known to dominate the microbial
      communities of sulfide deposits at and below the seafloor, their metabolic
      capabilities remain largely elusive. Here, we reveal the metabolic potential of
      these yet-uncultivated bacteria in hydrothermally inactive sulfide deposits
      collected at the Southern Mariana Trough by seafloor drilling. Near-complete
      genomes of the predominant bacterial members were recovered from shotgun
      metagenomic sequences. The genomic capabilities for CO2 and N2 fixation suggest
      that these bacteria are primary producers in the microbial ecosystem. Their
      genomes also encode versatile chemolithotrophic energy metabolisms, such as the
      oxidation of H2 , sulfide and intermediate sulfur species including thiosulfate,
      all of which can be supplied by chemical reactions between seawater and metal
      sulfides. Notably, the presence of genes involved in thiosulfate oxidation in
      Nitrospirae and Deltaproteobacteria genomes is unusual. Our study strongly
      support the presence of a chemosynthetic ecosystem fuelled by the Earth's
      internal energy in the deep-sea massive sulfide deposits, and illustrates the
      unexpected metabolic capability of known bacterial taxonomic groups.

PMID- 29322619
TI  - Randomized comparison of novel biodegradable polymer and durable polymer-coated
      cobalt-chromium sirolimus-eluting stents: Three-Year Outcomes of the I-LOVE-IT 2
      Trial.
AB  - OBJECTIVES: We aimed to compare the long-term outcomes of the novel biodegradable
      polymer cobalt-chromium sirolimus-eluting stent (BP-SES) versus the durable
      polymer sirolimus-eluting stent (DP-SES) in the I-LOVE-IT2 trial. BACKGROUNDS:
      Comparisons of the long-term safety and efficiency of the BP-DES versus the DP
      DES are limited. METHODS: A total of 2,737 patients eligible for coronary
      stenting were randomized to the BP-SES or DP-SES group at a 2:1 ratio. The
      primary endpoint of target lesion failure (TLF) was defined as a composite of
      cardiac death, target vessel myocardial infarction (MI), or clinically indicated
      target lesion revascularization. RESULTS: A three-year clinical follow-up period
      was available for 2,663 (97.3%) patients. There were no significant differences
      in TLF (8.9% vs. 8.6%, P = 0.81), patient-oriented composite endpoint (PoCE)
      (15.2% vs.14.5%, P = 0.63), or individual components between the BP-SES and DP
      SES. Definite/probable stent thrombosis (ST) was low and similar at 3 years (0.8%
      vs. 1.0%, P = 0.64). Landmark analysis of 1-3 years showed that the TLF (2.7% vs.
      2.6%, P = 0.81), PoCE (6.2% vs. 5.1%, P = 0.28), and definite/probable ST (0.4%
      vs. 0.4%, P = 1.00) were comparable between the 2 arms. CONCLUSIONS: In this
      prospective randomized trial, the BP-SES showed similar clinical results versus
      the DP-SES in terms of safety and efficacy outcomes over a 3-year follow-up
      period.

PMID- 29322620
TI  - Rice Protein Matrix Enhances Circulating Levels of Xanthohumol Following Acute
      Oral Intake of Spent Hops in Humans.
AB  - SCOPE: Xanthohumol (XN), a prenylated flavonoid found in hops, exhibits anti
      inflammatory and antioxidant properties. However, poor bioavailability may limit
      therapeutic applications. As food components are known to modulate polyphenol
      absorption, the objective is to determine whether a protein matrix could enhance
      the bioavailability of XN post oral consumption in humans. METHODS AND RESULTS:
      This is a randomized, double-blind, crossover study in healthy participants (n =
      6) evaluating XN and its major metabolites (isoxanthohumol [IX], 6- and 8
      prenylnaringenin [6-PN, 8-PN]) for 6 h following consumption of 12.4 mg of XN
      delivered via a spent hops-rice protein matrix preparation or a control spent
      hops preparation. Plasma XN and metabolites are measured by LC-MS/MS. Cmax , Tmax
      , and area-under-the-curve (AUC) values were determined. Circulating XN and
      metabolite response to each treatment was not bioequivalent. Plasma
      concentrations of XN and XN + metabolites (AUC) are greater with consumption of
      the spent hops-rice protein matrix preparation. CONCLUSION: Compared to a
      standard spent hops powder, a protein-rich spent hops matrix demonstrates
      enhanced plasma levels of XN and metabolites following acute oral intake.

PMID- 29322621
TI  - Reply: i-IFTA is better appreciated by its pathology rather than molecules.

PMID- 29322622
TI  - Ten years of clinical trial registration in a resource-limited setting:
      Experience of the Sri Lanka clinical trials registry.
AB  - AIM: We describe our experience of the first 10 years at the Sri Lanka Clinical
      Trials Registry (SLCTR). METHODS: We analyzed all trial records of the SLCTR over
      the study period. We collected information regarding trial characteristics and
      completeness of data entry in the SLCTR data set. RESULTS: During the study
      period, 210 trials (63% of all applications) were registered with the SLCTR. The
      number of registered trials showed an increasing trend over the years. All trial
      registrations had complete entries for all the data fields studied. Only 17.6% of
      the trials were registered retrospectively. All the registered trials were
      interventional studies, and the majority (87.6%) were randomized controlled
      trials. A significant proportion of trials (28.6%) were on noncommunicable
      diseases, and 12.4% were on pregnancy and its outcomes. Several trials (9.5%)
      were international collaborative studies. A majority of the Principal
      Investigators (70.9%) were affiliated to a university. Most of the studies
      (41.9%) were self-funded by the investigators. Details of ethics review committee
      approval were available for 96.7% of registered trials. Over a third of the
      registered trials (37.1%) had completed recruitment at the time of analysis. A
      majority of the trials (72.8%) had updated trial data since registration.
      CONCLUSIONS: There is a steady increase in the number of trials registered at the
      SLCTR. Complete entries for all the data fields were seen in all trial
      registrations. The SLCTR has made a positive contribution to the emergence of a
      healthy clinical research environment in Sri Lanka.

PMID- 29322623
TI  - Clinical practice guidelines in India: Quality appraisal and the use of evidence
      in their development.
AB  - BACKGROUND: Guideline development in India has come under increased scrutiny with
      a growing interest in the use of evidence for guideline development. METHODS:
      Guidelines on the four leading causes of disability adjusted life years in India
      (ischemic heart disease, lower respiratory infections, chronic obstructive
      pulmonary diseases, tuberculosis), published on or after 2010 was searched in
      electronic databases and by other methods and their quality appraised by using
      the AGREE-II appraisal tool. In-depth, semistructured interviews were conducted
      with 15 individuals involved with the development of the included guidelines and
      the transcripts were analyzed using the framework approach. RESULTS: We included
      eleven guidelines. The median AGREE II domain scores was highest for "scope and
      purpose" (81%) and "clarity of presentation" (76%), and lowest for "rigor of
      development" (31%) and "editorial independence" (33%). Four main themes emerged
      from the interviews: (1) Guideline development in India was undergoing transition
      toward adoption of systematic, transparent and evidence-based approaches but
      several barriers in the form of attitudes toward use of evidence, lack of
      methodological capacity, inadequate governance structure and funding exist; (2)
      guideline development was an academic activity restricted to elite institutions
      and this affects panel composition, the consultative process and implementation
      of guidelines; (3) mixed views on patient involvement in guideline development;
      and (4) Taboo & Poor understanding of issues surrounding conflict of interests.
      CONCLUSION: A multitude of efforts is needed by issuing agencies and the
      government to ensure development of guidelines in transparent, evidence-based and
      a systematic manner with high quality in India.

PMID- 29322624
TI  - Nasogastric tube and outcomes of Clostridium difficile infection: A systematic
      review and meta-analysis.
AB  - AIMS: Clostridium difficile infection (CDI) is a major concern for public health
      worldwide. Interestingly, the risk of poor clinical outcomes of CDI in patients
      with nasogastric tube (NGT) insertion is still controversial. The aim of this
      study was to assess the outcomes of CDI in patients with NGT insertion. METHODS:
      A literature search was performed using MEDLINE, EMBASE, and The Cochrane
      Database of Systematic Reviews from inception through November 2017. Studies that
      reported relative risks, odds ratios, or hazard ratios comparing the clinical
      outcome of CDI in patients with NGT versus those who did not were included.
      Pooled risk ratios (RR) and 95% confidence interval (CI) were calculated using a
      random-effect, generic inverse variance method. RESULTS: Eight observational
      studies were included in our analysis to assess the association between NGT
      insertion and risk of poor outcome of CDI. The pooled RR of severe or complicated
      clinical outcomes of CDI in patients with NGT insertion was 1.81 (95% CI: 1.17 to
      2.81). CONCLUSIONS: This study demonstrated a statistically significant
      association between NGT insertion and risk of poor outcomes of CDI. This finding
      may impact clinical management and primary prevention of CDI. Avoidance of
      unnecessary NGT uses would improve the clinical outcomes of CDI.

PMID- 29322625
TI  - Variations in dosimetric distribution and plan complexity with collimator angles
      in hypofractionated volumetric arc radiotherapy for treating prostate cancer.
AB  - PURPOSE: Hypofractionated radiotherapy can reduce treatment durations and produce
      effects identical to those of conventionally fractionated radiotherapy for
      treating prostate cancer. Volumetric arc radiotherapy (VMAT) can decrease the
      treatment machine monitor units (MUs). Previous studies have shown that VMAT with
      multileaf collimator (MLC) rotation exhibits better target dose distribution.
      Thus, VMAT with MLC rotation warrants further investigation. METHODS AND
      MATERIALS: Ten patients with prostate cancer were included in this study. The
      prostate gland and seminal vesicle received 68.75 and 55 Gy, respectively, in 25
      fractions. A dual-arc VMAT plan with a collimator angle of 0 degrees  was
      generated and the same constraints were used to reoptimize VMAT plans with
      different collimator angles. The conformity index (CI), homogeneity index (HI),
      gradient index (GI), normalized dose contrast (NDC), MU, and modulation
      complexity score (MCSV ) of the target were analyzed. The dose-volume histogram
      of the adjacent organs was analyzed. A Wilcoxon signed-rank test was used to
      compare different collimator angles. RESULTS: Optimum values of CI, HI, and MCSV
      were obtained with a collimator angle of 45 degrees . The optimum values of GI,
      and NDC were observed with a collimator angle of 0 degrees . In the rectum, the
      highest values of maximum dose and volume receiving 60 Gy (V60 Gy ) were obtained
      with a collimator angle of 0 degrees , and the lowest value of mean dose (Dmean )
      was obtained with a collimator angle of 45 degrees . In the bladder, high values
      of Dmean were obtained with collimator angles of 75 degrees  and 90 degrees . In
      the rectum and bladder, the values of V60 Gy obtained with the other tested
      angles were not significantly higher than those obtained with an angle of 0
      degrees . CONCLUSION: This study found that MLC rotation affects VMAT plan
      complexity and dosimetric distribution. A collimator angle of 45 degrees 
      exhibited the optimal values of CI, HI, and MCSv among all the tested collimator
      angles. Late side effects of the rectum and bladder are associated with high-dose
      volumes by previous studies. MLC rotation did not have statistically
      significantly higher values of V60 Gy in the rectum and bladder than did the 0
      degrees  angle. We thought a collimator angle of 45 degrees  was an optimal angle
      for the prostate VMAT treatment plan. The findings can serve as a guide for
      collimator angle selection in prostate hypofractionated VMAT planning.

PMID- 29322626
TI  - Restorations in primary teeth: a systematic review on survival and reasons for
      failures.
AB  - BACKGROUND: Several restorative materials with specific indications are used for
      filling cavities in primary teeth. AIM: To systematically review the literature
      in order to investigate the longevity of primary teeth restorations and the
      reasons for failure. DESIGN: Electronic databases were screened, and eligible
      studies were hand-searched to find longitudinal clinical studies evaluating the
      survival of restorations (class I, class II, and crown) placed with different
      materials in primary teeth with at least one year of follow-up. RESULTS: Thirty
      one studies were included, and a high bias risk was observed. Overall, 12,047
      restorations were evaluated with 12.5% of failure rate. A high variation on
      annual failure rate (AFR) was detected (0-29.9%). Composite resin showed the
      lowest AFRs (1.7-12.9%). Stainless steel crowns (SSC) had the highest success
      rate (96.1%). Class I restorations and restorations placed using rubber dam
      presented better AFR. The main reason for failure observed was secondary caries
      (36.5%). CONCLUSIONS: An elevated number of failures were observed due to
      recurrent caries, highlighting the need for professionals to work with a health
      promoting approach. The high variation on failure rate among the materials can be
      due to children's behavior during the procedure, which demands short dental
      appointments and a controlled environment.

PMID- 29322627
TI  - Safety and feasibility of laparoscopic reoperation for treatment of anastomotic
      leakage after laparoscopic colorectal cancer surgery.
AB  - INTRODUCTION: The safety and feasibility of laparoscopic reoperation for
      anastomotic leakage remain unclear. METHODS: A total of 3321 patients underwent
      laparoscopic surgery for primary colorectal cancer at a tertiary referral center
      from September 2002 to May 2016. Of these, 31 patients who underwent reoperation
      for treatment of anastomotic leakage were enrolled in this study and divided into
      two reoperation groups: laparoscopic (n = 15) and open (n = 16). Data regarding
      patient demographics, operative outcomes, morbidity, length of hospital stay,
      mortality, and stoma closure after reoperation in the two groups were compared.
      RESULTS: No significant difference was observed in the primary surgery procedure
      between the two groups. Estimated blood loss (1 vs 9 mL, P = 0.020), total
      postoperative complications (26.7% vs 68.8%, P = 0.032), wound infection (0.0% vs
      31.2%, P = 0.043), and postoperative hospital stay (18 vs 31 days, P = 0.017)
      were significantly better in the laparoscopic group than in the open group.
      Although the rate of stoma closure after reoperation was higher in the
      laparoscopic group, the difference was not significant (86.7% vs 62.5%, P =
      0.220). CONCLUSIONS: Laparoscopic reoperation exhibited better short-term
      outcomes than open reoperation for selected patients with anastomotic leakage.

PMID- 29322628
TI  - Case of cecal volvulus successfully treated with endoscopic colopexy.
AB  - We herein report a case of cecal volvulus successfully treated with endoscopic
      colopexy. A 73-year-old man with a high fever and abdominal fullness was
      diagnosed with ileus caused by cecal volvulus. CT showed a dilated cecum and
      small intestine without bowel strangulation as well as acute pneumonia. Because
      the pneumonia increased the risk associated with general anesthesia, we attempted
      decompression of the bowel using endoscopy to avoid surgery. On day 1, a
      transanal ileus tube was inserted to the terminal ileum through the dilated
      cecum. On day 7, the bowel torsion spontaneously released. On day 8, we performed
      percutaneous endoscopic colopexy to fix the cecum on the abdominal wall and
      prevent re-twisting. The patient was discharged on day 15 without postoperative
      complications. Percutaneous endoscopic colopexy for cecal volvulus may be a
      treatment option when the risk associated with general anesthesia or surgery is
      high because of a comorbidity.

PMID- 29322629
TI  - Material dependent fretting corrosion in spinal fusion devices: Evaluation of
      onset and long-term response.
AB  - Posterior spinal fusion implants include number of interconnecting components,
      which are subjected to micromotion under physiological loading conditions
      inducing a potential for fretting corrosion. There is very little known about the
      fretting corrosion in these devices in terms of the minimum angular displacement
      (threshold) necessary to induce fretting corrosion or the amount of fretting
      corrosion that can arise during the life of the implant. Therefore, the first
      goal was to evaluate the threshold fretting corrosion in three anatomical
      orientations and second the long-term fretting corrosion for the three different
      material types of spinal implants under physiological loading conditions. In
      threshold test, axial rotation exhibited highest changes in open circuit
      potential (VOCP in mV) and induced fretting currents (Ifrett in uA) for cobalt
      chrome (DeltaVOCP : 24.71 +/- 5.53; DeltaIfrett : 4.03 +/- 0.51) and stainless
      steel (DeltaVOCP : 28.21 +/- 6.97; DeltaIfrett : 2.98 +/- 0.42) constructs
      whereas it was flexion-extension for titanium constructs (DeltaVOCP : 4.51 +/-
      2.48; DeltaIfrett : 0.38 +/- 0.12). Long-term test indicated that the titanium
      (VOCP :101 +/- 0.06; Ifrett : 0.07 +/- 0.02) and cobalt chrome (VOCP : 140.67 +/-
      0.04; Ifrett : 0.12 +/- 0.05) constructs were more resistant to the fretting
      corrosion compared to stainless steel (VOCP : -135.33 +/- 0.31; Ifrett : 2.63 +/-
      1.06). (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater,
      106B: 2858-2868, 2018.

PMID- 29322630
TI  - Interlaboratory variability in the measurement of direct oral anticoagulants:
      results from the external quality assessment scheme.
AB  - : Essentials Tests for direct oral anticoagulants (DOACs) are not widely applied.
      These tests are perceived to be difficult to run and subjected to large between
      lab variation. We carried out proficiency testing surveys for DOAC testing in
      Italy. Interlab variability was small and similar to that of the international
      normalised ratio. SUMMARY: Background Tests for direct oral anticoagulants
      (DOACs) are not widely available. The perception that they are difficult to
      perform and are subject to large between-laboratory variation makes their
      implementation difficult. Aims We carried out proficiency-testing surveys for
      DOACs within the activity of the external quality-assessment scheme of the
      Italian Federation of Thrombosis Centers. Design Participants were provided with
      coded freeze-dried plasmas without or with graded concentrations of the three
      main DOACs, and asked to measure prothrombin time (PT), activated partial
      thromboplastin time (APTT), thrombin time and DOAC concentrations with dedicated
      tests. The results were centralized for statistical analysis. Results and
      conclusions All participants (n = 235) reported results for PT and APTT, and
      approximately one-third reported results for DOAC concentration. PT and APTT
      showed variable responsiveness to DOACs: PT was more responsive to rivaroxaban
      than to dabigatran or apixaban. APTT was more responsive to dabigatran than to
      rivaroxaban or apixaban. The thrombin time ratio (test/normal) was close to unity
      for plasmas without dabigatran, and was high (i.e. 7.6-fold or 15.4-fold longer
      than the plasma free from the drug) for plasmas containing dabigatran at low
      (i.e. 42 ng mL-1 ) or high (i.e. 182 ng mL-1 ) concentration. Dedicated tests
      were responsive to the respective drugs, and their interlaboratory variability
      was relatively small (overall coefficients of variation of 8.7%, 8.4% or 10.3%
      for dabigatran, rivaroxaban and apixaban, respectively) and was comparable to
      that observed within the same survey for the International Normalized Ratio (i.e.
      11.4%). In conclusion, tests for DOAC measurement performed reasonably well in a
      national quality-control scheme. Regulatory authorities should urgently issue
      recommendations on their use, and clinical laboratories should make them
      available.

PMID- 29322632
TI  - Approaches to sample size calculation for clinical trials in rare diseases.
AB  - We discuss 3 alternative approaches to sample size calculation: traditional
      sample size calculation based on power to show a statistically significant
      effect, sample size calculation based on assurance, and sample size based on a
      decision-theoretic approach. These approaches are compared head-to-head for
      clinical trial situations in rare diseases. Specifically, we consider 3 case
      studies of rare diseases (Lyell disease, adult-onset Still disease, and cystic
      fibrosis) with the aim to plan the sample size for an upcoming clinical trial. We
      outline in detail the reasonable choice of parameters for these approaches for
      each of the 3 case studies and calculate sample sizes. We stress that the
      influence of the input parameters needs to be investigated in all approaches and
      recommend investigating different sample size approaches before deciding finally
      on the trial size. Highly influencing for the sample size are choice of treatment
      effect parameter in all approaches and the parameter for the additional cost of
      the new treatment in the decision-theoretic approach. These should therefore be
      discussed extensively.

PMID- 29322631
TI  - Cold-inducible RNA binding protein in cancer and inflammation.
AB  - RNA binding proteins (RBPs) play key roles in RNA dynamics, including subcellular
      localization, translational efficiency and metabolism. Cold-inducible RNA binding
      protein (CIRP) is a stress-induced protein that was initially described as a DNA
      damage-induced transcript (A18 hnRNP), as well as a cold-shock domain containing
      cold-stress response protein (CIRBP) that alters the translational efficiency of
      its target messenger RNAs (mRNAs). This review summarizes recent work on the
      roles of CIRP in the context of inflammation and cancer. The function of CIRP in
      cancer appeared to be solely driven though its functions as an RBP that targeted
      cancer-associated mRNAs, but it is increasingly clear that CIRP also modulates
      inflammation. Several recent studies highlight roles for CIRP in immune
      responses, ranging from sepsis to wound healing and tumor-promoting inflammation.
      While modulating inflammation is an established role for RBPs that target
      cytokine mRNAs, CIRP appears to modulate inflammation by several different
      mechanisms. CIRP has been found in serum, where it binds the TLR4-MD2 complex,
      acting as a Damage-associated molecular pattern (DAMP). CIRP activates the NF
      kappaB pathway, increasing phosphorylation of Ikappakappa and IkappaBalpha, and
      stabilizes mRNAs encoding pro-inflammatory cytokines. While CIRP promotes higher
      levels of pro-inflammatory cytokines in certain cancers, it also decreases
      inflammation to accelerate wound healing. This dichotomy suggests that the
      influence of CIRP on inflammation is context dependent and highlights the
      importance of detailing the mechanisms by which CIRP modulates inflammation.
      WIREs RNA 2018, 9:e1462. doi: 10.1002/wrna.1462 This article is categorized
      under: RNA in Disease and Development > RNA in Disease RNA Interactions with
      Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications.

PMID- 29322633
TI  - Preclinical evaluation of melanocyte transplantation by chitosan-based melanocyte
      spheroid patch to skin prepared by controlled sunburn blistering.
AB  - Transplantation of autologous cultured melanocytes as cell suspension has been
      used for the treatment of vitiligo. The recipient site is often prepared by laser
      mediated dermabrasion. Such procedures encounter disadvantages including
      prolonged transplantation duration, unsecured cell adherence to lesional skin and
      potential scarring. To improve this, here we propose a method by preparing
      recipient sites before transplantation by psoralen and ultraviolet A (PUVA)
      induced sunburn followed by transplanting cells with a chitosan-based melanocyte
      spheroid patch. We evaluated the method in nude mice. Application of methoxsalen
      soaked filter paper on skin for 30 min followed by ultraviolet A exposure induced
      controlled sunburn blisters in 2 days. Upon transplantation, the blister roof
      could be quickly peeled off by a waxing patch. The chitosan membrane on which
      melanocytes were precultured into multicellular spheroids was transplanted with
      cells facing the skin. The chitosan patch adhered well to skin and secured the
      contact of melanocytes with the recipient site. One day later, melanocyte
      spheroids already detached from the chitosan membrane and adhered to the
      recipient skin. Our results suggest that the combination of chitosan-based
      melanocyte spheroid patch with epidermal ablation by PUVA-induced sunburn
      reaction can be a feasible method to facilitate melanocyte transplantation. (c)
      2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2535
      2543, 2018.

PMID- 29322634
TI  - Structure-Property Relations in Carbon Nanotube Fibers by Downscaling Solution
      Processing.
AB  - At the microscopic scale, carbon nanotubes (CNTs) combine impressive tensile
      strength and electrical conductivity; however, their macroscopic counterparts
      have not met expectations. The reasons are variously attributed to inherent CNT
      sample properties (diameter and helicity polydispersity, high defect density,
      insufficient length) and manufacturing shortcomings (inadequate ordering and
      packing), which can lead to poor transmission of stress and current. To
      efficiently investigate the disparity between microscopic and macroscopic
      properties, a new method is introduced for processing microgram quantities of
      CNTs into highly oriented and well-packed fibers. CNTs are dissolved into
      chlorosulfonic acid and processed into aligned films; each film can be peeled and
      twisted into multiple discrete fibers. Fibers fabricated by this method and
      solution-spinning are directly compared to determine the impact of alignment,
      twist, packing density, and length. Surprisingly, these discrete fibers can be
      twice as strong as their solution-spun counterparts despite a lower degree of
      alignment. Strength appears to be more sensitive to internal twist and packing
      density, while fiber conductivity is essentially equivalent among the two sets of
      samples. Importantly, this rapid fiber manufacturing method uses three orders of
      magnitude less material than solution spinning, expanding the experimental
      parameter space and enabling the exploration of unique CNT sources.

PMID- 29322635
TI  - The effect of cell density, proximity, and time on the cytotoxicity of magnesium
      and galvanically coupled magnesium-titanium particles in vitro.
AB  - Magnesium (Mg) and galvanically coupled magnesium-titanium (Mg-Ti) particles in
      vitro have been reported previously to kill cells in a dosage-dependent manner.
      Mg-Ti particles kill cells more effectively than Mg alone, due to the galvanic
      effect of Mg and Ti. This study further investigated the in vitro cytotoxicity of
      Mg and Mg-Ti in terms of particle concentration, cell density, time, and
      proximity. Cell density has an effect on cell viability only at low particle
      concentrations (below 250 ug/mL), where cell viability dropped only for lower
      cell densities (5000-10,000 cells/cm2 ) and not for higher cell densities (20,000
      30,000 cells/cm2 ), showing that the particles cannot kill if there are more
      cells present. Cytotoxicity of Mg and Mg-Ti particles is quick and temporary,
      where the particles kill cells only during particle corrosion (first 24 h).
      Depending on the percentage of surviving cells, particle concentrations, and
      ongoing corrosion activity, the remaining live cells either proliferated and
      recovered, or just remained viable and quiescent. The particle killing is also
      proximity-dependent, where cell viability was significantly higher for cells far
      away from the particles (greater than ~1 mm) compared to those close to the
      particles (less than ~1 mm). Although the increase of pH does affect cell
      viability negatively, it is not the sole killing factor since cell viability is
      significantly dependent on particle type and proximity but not pH. Mg and Mg-Ti
      particles used in this study are large enough to prevent direct cell phagocytosis
      so that the cell killing effect may be attributed to solely electrochemical
      reactions. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1428
      1439, 2018.

PMID- 29322636
TI  - Lower urinary tract dysfunction in pediatric patients after ureteroneocystostomy
      due to vesicoureteral reflux: Long-term follow-up.
AB  - OBJECTIVE: The aim of the present study was to evaluate long-term lower urinary
      tract dysfunction (LUTD) in pediatric patients who underwent ureteroneocystostomy
      due to vesicoureteral reflux. METHODS: The present retrospective study was
      performed on 61 patients. Patients were divided into 3 groups: Group 1 (n = 26),
      did not have LUTD; Group 2 (n = 23), had LUTD; and Group 3 (n = 12), was not
      toilet trained preoperatively. Patients were reassessed regarding de novo LUTD or
      the persistence of LUTD at least 7 years after the ureteroneocystostomy. RESULTS:
      Mean patient age was 7 years (range 1-15) when ureteroneocystostomy was performed
      and the surgery was associated with a 92% success rate. The mean follow-up period
      was 10 years (range 7-12 years). Postoperative LUTD was present in 6 (23%), 12
      (52%), and 1 (8.3%) patients in Groups 1, 2, and 3, respectively. The presence of
      LUTD before surgery and bilateral repair in the same setting were predictive risk
      factors for the presence of LUTD during the long-term follow-up. LUTD occurred at
      higher rate in Group 2 than in Groups 1 and 3 (52% vs. 23% and 8.3%,
      respectively; P = .015). The presence of de novo LUTD was significant in Group 1
      compared with the presence of preoperative and postoperative LUTD (P = .031,
      Wilcoxon analysis). CONCLUSIONS: LUTD may not resolve after a
      ureteroneocystostomy, and additional therapy could be necessary. Due to the
      probability of damage to the ureterovesical nerve and/or disturbed bladder
      dynamics, de novo LUTD may occur in patients with bilateral high-grade reflux
      without LUTD before a ureteroneocystostomy.

PMID- 29322637
TI  - Maternal exposures and risk of oral clefts in South Vietnam.
AB  - BACKGROUND: Oral clefts are among the most common congenital anomalies. Most
      studies on risk factors of oral clefts have been carried out in developed
      countries. We investigated the associations between maternal exposures in the
      first trimester and oral clefts in South Vietnam. METHODS: We conducted a
      hospital-based case-control study during October 2014-November 2015. Cases
      included 170 patients with nonsyndromic cleft lip with or without cleft palate
      and those with cleft palate only. Controls were 170 children without oral clefts,
      matched to each case by age and gender. Mothers were interviewed using structured
      questionnaire. We performed conditional logistic regression to estimate odds
      ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Passive smoking was
      associated with increased risk of oral clefts in univariate analysis, but not in
      multivariable analysis (adjusted OR [aOR] = 1.68; 95% CI, 0.53-5.37). No
      association was observed between liver intake and oral clefts. Compared with
      nondrinkers, mothers who reported consumption of caffeine-containing beverages
      were more likely to have an infant with oral cleft (aOR = 5.89; 95% CI, 1.08
      32.00). Periconceptional use of folic acid and multivitamins supplementation was
      associated with reduced risk of oral clefts (aOR = 0.01; 95% CI, 0.00-0.09 and
      aOR = 0.03; 95% CI, 0.01-0.13, respectively). CONCLUSIONS: The results suggest no
      associations of maternal passive smoking or liver intake with oral clefts.
      Periconceptional use of folic acid or multivitamins may protect against oral
      clefts. Further studies are warranted to examine the roles of caffeine
      consumption in pregnant mothers on occurrence of oral clefts in offspring.

PMID- 29322638
TI  - Comparative evaluation of the use of magnification loupes in supragingival
      scaling procedures.
AB  - AIM: The main aim of the present investigation was to evaluate clinical and
      patient-centered outcomes of supragingival scaling performed with or without the
      use of 2.5* magnification loupes and illumination. METHODS: A total of 30
      patients, divided into three groups, were treated with 2.5* loupes and 2.5*
      loupes and illumination, and without any magnification device. Full-mouth plaque
      score percentage (FMPS%) and full-mouth bleeding score percentage (FMBS%) were
      registered before and after the treatment. Moreover, perceived pain and quality
      of the treatment were recorded using a visual analog scale. Appropriate
      statistical analysis was adopted to analyze between-group differences for the
      investigated parameters. RESULTS: All of the patients completed the study
      protocol. All the groups were homogeneous at baseline. Supragingival scaling
      caused a significant reduction of FMPS% and FMBS% in all groups without
      differences among them. Moreover, no differences could be found for patient
      centered outcomes. The duration of the treatment was significantly higher in the
      group in which loupes and illumination was used than in the control group.
      CONCLUSIONS: The use of magnification loupes (with or without illumination) did
      not significantly improve clinical and patient-centered outcomes of supragingival
      scaling procedures.

PMID- 29322639
TI  - Prokaryotes in the WAIS Divide ice core reflect source and transport changes
      between Last Glacial Maximum and the early Holocene.
AB  - We present the first long-term, highly resolved prokaryotic cell concentration
      record obtained from a polar ice core. This record, obtained from the West
      Antarctic Ice Sheet (WAIS) Divide (WD) ice core, spanned from the Last Glacial
      Maximum (LGM) to the early Holocene (EH) and showed distinct fluctuations in
      prokaryotic cell concentration coincident with major climatic states. The time
      series also revealed a ~1,500-year periodicity with greater amplitude during the
      Last Deglaciation (LDG). Higher prokaryotic cell concentration and lower
      variability occurred during the LGM and EH than during the LDG. A sevenfold
      decrease in prokaryotic cell concentration coincided with the LGM/LDG transition
      and the global 19 ka meltwater pulse. Statistical models revealed significant
      relationships between the prokaryotic cell record and tracers of both marine (sea
      salt sodium [ssNa]) and burning emissions (black carbon [BC]). Collectively,
      these models, together with visual observations and methanosulfidic acid (MSA)
      measurements, indicated that the temporal variability in concentration of
      airborne prokaryotic cells reflected changes in marine/sea-ice regional
      environments of the WAIS. Our data revealed that variations in source and
      transport were the most likely processes producing the significant temporal
      variations in WD prokaryotic cell concentrations. This record provided strong
      evidence that airborne prokaryotic cell deposition differed during the LGM, LDG,
      and EH, and that these changes in cell densities could be explained by different
      environmental conditions during each of these climatic periods. Our observations
      provide the first ice-core time series evidence for a prokaryotic response to
      long-term climatic and environmental processes.

PMID- 29322640
TI  - Conserved roles of Osiris genes in insect development, polymorphism and
      protection.
AB  - Much of the variation among insects is derived from the different ways that
      chitin has been moulded to form rigid structures, both internal and external. In
      this study, we identify a highly conserved expression pattern in an insect-only
      gene family, the Osiris genes, that is essential for development, but also plays
      a significant role in phenotypic plasticity and in immunity/toxicity responses.
      The majority of Osiris genes exist in a highly syntenic cluster, and the cluster
      itself appears to have arisen very early in the evolution of insects. We used
      developmental gene expression in the fruit fly, Drosophila melanogaster, the
      bumble bee, Bombus terrestris, the harvester ant, Pogonomyrmex barbatus, and the
      wood ant, Formica exsecta, to compare patterns of Osiris gene expression both
      during development and between alternate caste phenotypes in the polymorphic
      social insects. Developmental gene expression of Osiris genes is highly conserved
      across species and correlated with gene location and evolutionary history. The
      social insect castes are highly divergent in pupal Osiris gene expression. Sets
      of co-expressed genes that include Osiris genes are enriched in gene ontology
      terms related to chitin/cuticle and peptidase activity. Osiris genes are
      essential for cuticle formation in both embryos and pupae, and genes co-expressed
      with Osiris genes affect wing development. Additionally, Osiris genes and those
      co-expressed seem to play a conserved role in insect toxicology defences and
      digestion. Given their role in development, plasticity, and protection, we
      propose that the Osiris genes play a central role in insect adaptive evolution.

PMID- 29322641
TI  - Case of laparoscopic right hemicolectomy for ascending colon cancer after aortic
      graft replacement and revascularization of the superior mesenteric artery.
AB  - A 67-year-old man who presented with a bloody stool was diagnosed with ascending
      colon cancer. He had previously experienced thoracic and abdominal aortic
      dissections, which were treated with thoracic and abdominal aortic grafts and
      superior mesenteric artery revascularization. We performed a laparoscopic right
      hemicolectomy with a D3 lymph node dissection. During the laparotomy, we
      identified the superior mesenteric artery and an enlarged anterior superior
      pancreaticoduodenal artery. Injury to the latter artery could lead to severe
      ischemia in multiple organs; therefore, it was crucial to identify the primary
      feeding artery and vascular anatomy before and during surgery. We chose the
      laparoscopic right hemicolectomy to avoid injuring the anterior superior
      pancreaticoduodenal artery and the intra-abdominal abscess. This case study was
      the first to describe a laparoscopic hemicolectomy after thoracic and abdominal
      aortic grafts and superior mesenteric artery revascularization.

PMID- 29322642
TI  - Peste des petits ruminants in China since its first outbreak in 2007: A 10-year
      review.
AB  - Peste des petits ruminants (PPR) is a highly infectious disease of small
      ruminants and caused by small ruminant morbillivirus (SRMV), formerly called
      peste-des-petits-ruminants virus (PPRV). This disease is circulating in Africa
      (except most countries in southern Africa), the Arabian Peninsula, the Middle
      East, and Central, East and South-East Asia. Peste des petits ruminants is still
      regarded as an exotic disease in China, where its first outbreak was reported in
      the Ngari region of Tibet in 2007, but effectively controlled by slaughter,
      vaccination and animal movement restriction in PPR-infected areas. However, PPR
      re-emerged in Xinjiang of China in December 2013, rapidly spread into much of
      China in the first half of 2014, but since then was substantially inhibited
      countrywide. Phylogenetic analysis shows that SRMVs from China share the highest
      homology with others from its neighbouring countries, possibly indicating the
      transboundary transmission of SRMVs. In 2015, a national eradication program for
      PPR was issued and has been being implemented in China, expecting to achieve a
      PPR-eradicating aim countrywide by 2020. Here, we reviewed a 10-year history
      (2007-2017) of PPR in China, including two major outbreaks, its infection in wild
      species, development of diagnostics and vaccines, and implementation of the
      national eradication program.

PMID- 29322644
TI  - Rosemary, Castor Oils, and Propolis Extract: Activity Against Candida Albicans
      and Alterations on Properties of Dental Acrylic Resins.
AB  - PURPOSE: To evaluate the in vitro activity of 8% rosemary, 2% castor oils, and
      12% propolis glycolic extract against Candida albicans, as well as the physical
      changes of properties in colorless and pink acrylic resins after immersion in
      these liquids. MATERIALS AND METHODS: Colorimetric, roughness, and Knoop
      microhardness assays were evaluated in 25 specimens distributed into five groups
      (3 test groups and 2 control groups - distilled water and hypochlorite 1%),
      totaling five specimens per group for each acrylic resin (colorless and pink).
      The specimens were individually immersed for 30 minutes in 10 mL of these
      liquids, washed, and dried once a week. They were maintained in distilled water
      at 37 degrees C between processes during all experiments. The analyses were
      performed before immersion and in the 4th and/or 12th month. In vitro, 18 acrylic
      resins were exposed to C. albicans and, after a process of 30 minutes in
      immersion in the five groups cited and oil vehicle control of vesicle (liquid
      Vaseline), the specimens were washed and incubated for 24 hours in 37 degrees C.
      The growth was determined by colony counting. For comparisons between the groups
      in each trial and the disinfection test, paired Student's t-tests and ANOVA with
      post hoc Tukey were performed by the SPSS program, considering alpha = 0.05.
      RESULTS: None of the liquids altered the microhardness, but all the natural
      compounds and 1% sodium hypochlorite (control) altered color and roughness after
      the 12th month of immersion in these agents. In the colorless specimens, 8%
      rosemary oil caused a color change similar to water, and less color and roughness
      alterations when compared to 2% castor oil and 1% sodium hypochlorite,
      respectively. There was no growth of yeast colonies after immersion in rosemary
      oil, propolis glycolic extract, and 1% sodium hypochlorite. CONCLUSION: Eight
      percent rosemary oil has the potential to be used as an acrylic resin
      disinfectant.

PMID- 29322643
TI  - Disparities in cancer outcomes across age, sex, and race/ethnicity among patients
      with pancreatic cancer.
AB  - Age, sex, and racial/ethnic disparities exist, but are understudied in pancreatic
      adenocarcinoma (PDAC). We used the Surveillance, Epidemiology, and End Results
      (SEER)-Medicare linked database to determine whether survival and treatment
      disparities persist after adjusting for demographic and clinical characteristics.
      Our study included PDAC patients diagnosed between 1992 and 2011. We used Cox
      regression to compare survival across age, sex, and race/ethnicity within early
      stage and late-stage cancer subgroups, adjusting for marital status, urban
      location, socioeconomics, SEER region, comorbidities, stage, lymph node status,
      tumor location, tumor grade, diagnosis year, and treatment received. We used
      logistic regression to compare differences in treatment received across age, sex,
      and race/ethnicity. Among 20,896 patients, 84% were White, 9% Black, 5% Asian,
      and 2% Hispanic. Median age was 75; 56% were female and 53% had late-stage
      cancer. Among early-stage patients in the adjusted Cox model, older patient
      subgroups had worse survival compared with ages 66-69 (HR > 1.1, P < 0.01 for
      groups >69); no survival differences existed between sexes. Black (HR = 1.1, P =
      0.01) and Hispanic (HR = 1.2, P < 0.01) patients had worse survival compared with
      White. Among late-stage cancer patients, patients over age 84 had worse survival
      than those aged 66-69 (HR = 1.1, P < 0.01), and males (HR = 1.08, P < 0.01) had
      worse survival than females; there were no racial/ethnic differences. Older age
      and minority race/ethnicity were associated with lower likelihood of receiving
      chemotherapy, radiation, and/or surgery. Age and racial/ethnic disparities in
      survival outcomes and treatment received exist for PDAC patients; these
      disparities persist after adjusting for differences in demographic and clinical
      characteristics.

PMID- 29322645
TI  - Faecal Escherichia coli as biological indicator of spatial interaction between
      domestic pigs and wild boar (Sus scrofa) in Corsica.
AB  - On the Mediterranean island of Corsica, cohabitation between sympatric domestic
      pigs and Eurasian wild boar (Sus scrofa) is common and widespread and can
      facilitate the maintenance and dissemination of several pathogens detrimental for
      the pig industry or human health. In this study, we monitored a population of
      free-ranging domestic pigs reared in extensive conditions within a 800-ha
      property located in Central Corsica which was frequently visited by a sympatric
      population of wild boar between 2013 and 2015. We used GPS collars to assess
      evidence of a spatially shared environment. Subsequently, we analysed by PFGE of
      XbaI-restricted DNA if those populations shared faecal Escherichia coli clones
      that would indicate contact and compared these results with those collected in a
      distant (separated by at least 50 km) population of wild boar used as control.
      Results showed that one of eight wild boars sampled in the study area shed E.
      coli XbaI clones identical to clones isolated from domestic pig sounders from the
      farm, while wild boar populations sampled in distant parts of the study area
      shared no identical clone with the domestic pigs monitored. Interestingly, within
      the sampled pigs, two identical clones were found in 2013 and in 2015, indicating
      a long-time persisting colonization type. Although the method of isolation of E.
      coli and PFGE typing of the isolates requires intensive laboratory work, it is
      applicable under field conditions to monitor potential infectious contacts. It
      also provides evidence of exchange of microorganisms between sympatric domestic
      pigs and wild boar populations.

PMID- 29322647
TI  - Max Bergmann award lecture:Macromolecular medicinal chemistry as applied to
      metabolic diseases.
AB  - This review presents the scope of research presented in an October 2016 lecture
      pertaining to the award of the 2015 Max Bergmann Medal. The advancement in
      synthetic and biosynthetic chemistry as applied to the discovery of novel
      macromolecular drug candidates is reviewed. The evolution of the technology from
      the design, synthesis, and development of the first biosynthetic peptides through
      the emergence of peptide-based incretin agonists that function by multiple
      biological mechanisms is exemplified by the progression of such peptides from
      preclinical to clinical study. A closing section highlights recent progress made
      in total chemical synthesis of insulin and related peptides.

PMID- 29322646
TI  - Comparison of hook wire versus coil localization for video-assisted thoracoscopic
      surgery.
AB  - BACKGROUND: A hook wire has been most widely used for computed tomography (CT)
      guided localization before video-assisted thoracoscopic surgery (VATS). However,
      microcoils have been suggested to replace wires. The purpose of this study was to
      compare the efficacy, VATS procedure time, and excised volume of specimens of CT
      guided localization using a hook wire and microcoil. METHODS: The medical records
      of 106 patients with 110 pulmonary nodules who underwent CT-guided localization
      using a hook wire (group A) or microcoil (group B) before VATS performed between
      March 2013 and January 2017 were retrospectively reviewed. RESULTS: The procedure
      success rate was 100% in both groups. Dislodgement occurred in four patients in
      group A and not in group B. Patient pain score was significantly lower for group
      B than group A (4.0 vs. 6.3; P < 0.001). The VATS success rate was higher in
      group B than in group A (98.1% vs. 91.1%; P = 0.174). The VATS procedure time was
      significantly shorter for group B than group A (18.8 vs. 23.6 minutes; P =
      0.004). The excised volume of surgical specimens was significantly smaller for
      group B than group A (8.5 vs. 11.7 cm3 ; P = 0.043). No major complications
      related to the localization procedure were noted in either group. CONCLUSIONS:
      This study showed similar effectiveness of VATS localization between groups.
      However, microcoil is superior to hook wire for localization of pulmonary nodules
      in terms of VATS procedure time and excised volume of surgical specimens, with
      the advantages of no dislodgement and less patient pain.

PMID- 29322648
TI  - Max-Bergmann award lecture:A RaPID way to discover bioactive nonstandard peptides
      assisted by the flexizyme and FIT systems.
AB  - Although general review articles should cover various people's achievements
      related to the subject, this review is privileged to describe the technology
      developed by Suga (and colleagues) as a recipient of the Max-Bergmann Medal in
      2016. The technology consists of 3 unique and essential tools, flexizymes, FIT,
      and RaPID systems. This review describes the history of the development of each
      tool and discusses the recent applications of the RaPID system to discover potent
      nonstandard peptides for therapeutic and diagnostic uses.

PMID- 29322649
TI  - Design, expression, and characterization of the hybrid antimicrobial peptide T
      catesbeianin-1 based on FyuA.
AB  - The overuse of antibiotics has resulted in the emergence of antibiotic-resistant
      bacteria, which presents an urgent need for new antimicrobial agents. At present,
      antimicrobial peptides have attracted a great deal of attention from researchers.
      However, antimicrobial peptides often affect a broad range of microorganisms,
      including the normal flora in a host organism. In the present study, we designed
      a novel hybrid antimicrobial peptide, expressed the hybrid peptide, and studied
      its specific target. The hybrid peptide, named T-catesbeianin-1, which includes
      the FyuA-binding domain of pesticin and the peptide catesbeianin-1, was designed
      and expressed in Pichia pastoris X-33. Then, we determined the antimicrobial
      activity, cytotoxicity, and specific target of the peptide. T-catesbeianin-1 has
      strong antimicrobial activity and binds to FyuA to inhibit or kill Escherichia
      coli present in clinical specimens and mixed-species culture. In summary, these
      findings suggested that T-catesbeianin-1 might be promising and specific
      antibiotic agent for therapeutic application against fyuA+ E. coli.

PMID- 29322650
TI  - Molecular characterization of the beta-amyloid(4-10) epitope of plaque specific
      Abeta antibodies by affinity-mass spectrometry using alanine site mutation.
AB  - Alzheimer disease is a neurodegenerative disease affecting an increasing number
      of patients worldwide. Current therapeutic strategies are directed to molecules
      capable to block the aggregation of the beta-amyloid(1-42) (Abeta) peptide and
      its shorter naturally occurring peptide fragments into toxic oligomers and
      amyloid fibrils. Abeta-specific antibodies have been recently developed as
      powerful antiaggregation tools. The identification and functional
      characterization of the epitope structures of Abeta antibodies contributes to the
      elucidation of their mechanism of action in the human organism. In previous
      studies, the Abeta(4-10) peptide has been identified as an epitope for the
      polyclonal anti-Abeta(1-42) antibody that has been shown capable to reduce
      amyloid deposition in a transgenic Alzheimer disease mouse model. To determine
      the functional significance of the amino acid residues involved in binding to the
      antibody, we report here the effects of alanine single-site mutations within the
      Abeta-epitope sequence on the antigen-antibody interaction. Specific
      identification of the essential affinity preserving mutant peptides was obtained
      by exposing a Sepharose-immobilized antibody column to an equimolar mixture of
      mutant peptides, followed by analysis of bound peptides using high-resolution
      MALDI-Fourier transform-Ion Cyclotron Resonance mass spectrometry. For the
      polyclonal antibody, affinity was preserved in the H6A, D7A, S8A, and G9A mutants
      but was lost in the F4, R5, and Y10 mutants, indicating these residues as
      essential amino acids for binding. Enzyme-linked immunosorbent assays confirmed
      the binding differences of the mutant peptides to the polyclonal antibody. In
      contrast, the mass spectrometric analysis of the mutant Abeta(4-10) peptides upon
      affinity binding to a monoclonal anti-Abeta(1-17) antibody showed complete loss
      of binding by Ala-site mutation of any residue of the Abeta(4-10) epitope.
      Surface plasmon resonance affinity determination of wild-type Abeta(1-17) to the
      monoclonal Abeta antibody provided a binding constant KD in the low nanomolar
      range. These results provide valuable information in the elucidation of the
      binding mechanism and the development of Abeta-specific antibodies with improved
      therapeutic efficacy.

PMID- 29322652
TI  - Introducing the new journal design for the Journal of Peptide Science.

PMID- 29322651
TI  - Antifungal dipeptides incorporating an inhibitor of homoserine dehydrogenase.
AB  - The antifungal activity of 5-hydroxy-4-oxo-l-norvaline (HONV), exhibited under
      conditions mimicking human serum, may be improved upon incorporation of this
      amino acid into a dipeptide structure. Several HONV-containing dipeptides
      inhibited growth of human pathogenic yeasts of the Candida genus in the RPMI-1640
      medium, with minimal inhibitory concentration values in the 32 to 64 MUg mL-1
      range. This activity was not affected by multidrug resistance that is caused by
      overexpression of genes encoding drug efflux proteins. The mechanism of
      antifungal action of HONV dipeptides involved uptake by the oligopeptide
      transport system, subsequent intracellular cleavage by cytosolic peptidases, and
      inhibition of homoserine dehydrogenase by the released HONV. The relative
      transport rates determined the anticandidal activity of HONV dipeptides.

PMID- 29322654
TI  - Brand-to-generic levetiracetam switching: a 4-year prospective observational real
      life study.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to determine whether
      switching from branded levetiracetam (Keppra(r) ) to a levetiracetam generic
      equivalent product (Matever(r) ) in an epilepsy cohort could provide adequate
      results in terms of seizure control and tolerability. METHODS: To be eligible for
      the study, patients had to have been taking Keppra(r) as monotherapy or
      polytherapy for at least 6 months. Between March 2013 and April 2017, patients
      were invited to switch to Matever(r) as part of their follow-up. We evaluated the
      number of seizures per month, drug-related adverse events and
      electroencephalography before the switch (T0, baseline) and 6 months after
      switching (T1). Furthermore, we reported the long-term follow-up of patients who
      continued to use Matever(r) after the end of the study, considering the most
      recent visit for each patient (T2). RESULTS: A total of 55 patients refused the
      switch. Among the remaining 125 patients, 59 (47%) were treated using Keppra(r)
      as monotherapy and 66 (53%) were on Keppra(r) as polytherapy. All 125 patients
      were subjected to switching from Keppra(r) to Matever(r) . Comparing patients
      before (T0) and after (T1) switching, we found no statistically significant
      differences in terms of seizure frequency and occurrence of adverse effects.
      There were no significant differences (number of seizures/month and drug-related
      adverse events) between patients treated with Matever(r) as monotherapy and
      patients who refused the switch and continued to use Keppra(r) as monotherapy for
      a long-term follow-up of 48 months. Electroencephalography findings were also
      unchanged. CONCLUSION: In our sample, brand-to-generic levetiracetam switching
      was effective and safe in both monotherapy and polytherapy regardless of the
      epilepsy syndrome.

PMID- 29322656
TI  - Iatrogenic punctal prolapse.

PMID- 29322655
TI  - Efficiency of Er:YAG laser in debonding of porcelain laminate veneers by contact
      and non-contact laser application modes (in vitro study).
AB  - OBJECTIVE: To determine the efficiency of debonding porcelain laminate veneers
      (PLV) by using several laser parameters and two different application modes of
      Er:YAG laser [contact (CM) and non-contact (NCM)], by verification of the
      consumed PLV debonding time and the changes in dental pulp temperature. MATERIALS
      AND METHODS: Forty extracted non-carious human maxillary premolars were prepared
      for receiving PLV. Sixteen of them were divided into two groups, each of them
      comprised eight samples based on the application mode; group A with NCM, and
      group B with CM. Veneers of both groups were debonded by the same laser
      parameters (360 mJ, 15 Hz) during loading of a 15 N force on specially fabricated
      veneer cervical margins. The primary results showed that the NCM was more
      efficient, thus, additional groups (C, D, and E) of the same mode and number of
      samples were tested with different laser parameters of energy and frequency;
      group C (400 mJ, 10 Hz), group D (270 mJ, 15 Hz), group E (300 mJ, 10 Hz). The
      failure mode was determined and classified for the debonded samples of all
      groups. RESULTS: All veneers were debonded and samples of the NCM group had
      considerably lower debonding time (12.6 seconds) than the CM samples (96.3
      seconds), however, higher changes of temperature in NCM (4.2 degrees C) than in
      CM were observed (2.9 degrees C). The failure mode of samples was either type 1
      or 3. CONCLUSION: Er:YAG laser is an effective tool in debonding PLVs. The NCM
      application mode was more efficient in reducing debonding time than CM
      application mode but with a higher change in pulp temperature. CLINICAL
      SIGNIFICANCE: Investigating the efficacy of Er:YAG laser as a non-invasive
      particle technique for debonding of failed or malpositioned of porcelain
      laminated veneers.

PMID- 29322657
TI  - Polyetheretherketone Overlay Prosthesis over High Noble Ball Attachments to
      Overcome Base Metal Sensitivity: A Clinical Report.
AB  - A modified polyetheretherketone (PEEK) framework material in combination with
      heat-polymerized denture base acrylic resin was used for the fabrication of an
      overlay prosthesis for a patient sensitive to base metals. High noble metal was
      used for the fabrication of the post/coping/ball attachment assemblies to promote
      retention and stability. These protruding attachments into the acrylic resin
      could result in stress concentration; therefore, a framework is often used to
      strengthen the prosthesis. PEEK frameworks could be a treatment alternative to
      high noble or Ti frameworks since they combine good mechanical properties with
      biocompatibility, reduced cost, and common laboratory procedures.

PMID- 29322653
TI  - Viruses associated with congenital tremor and high lethality in piglets.
AB  - The recently described atypical porcine pestivirus (APPV) has been associated
      with congenital tremor (CT) type A-II in piglets in different countries. Another
      important neurological pathogen of pigs is porcine teschovirus (PTV), which has
      been associated with non-suppurative encephalomyelitis in pigs with severe or
      mild neurological disorders. There have been no reports of APPV and/or PTV
      coinfection associated with CT or encephalomyelitis in Brazilian pig herds. The
      aim of this study was to describe the pathological and molecular findings
      associated with simultaneous infection of APPV and PTV in piglets with clinical
      manifestations of CT that were derived from a herd with high rates of CT
      associated lethality. In 2017, three piglets from the same litter with CT died
      spontaneously. The principal pathological alterations in all piglets were
      secondary demyelination and hypomyelination at the cerebellum, brainstem and
      spinal cord confirmed by histopathology and luxol fast blue-cresyl violet stain.
      Additional significant pathological findings included multifocal neuronal
      necrosis, neuronophagia and gliosis found in the cerebral cortex and spinal cord
      of all piglets, while atrophic enteritis and mesocolonic oedema were observed in
      some of them. APPV and PTV RNA were detected in the central nervous system of
      affected piglets, and PTV was also detected in the intestine and faeces. The
      pathological alterations and molecular findings together suggest a dual infection
      due to APPV and PTV at this farm. Moreover, the combined effects of these
      pathogens can be attributed to the elevated piglet mortality, as coinfections
      involving PTV have a synergistic effect on the affected animals.

PMID- 29322658
TI  - Successful resection to treat idiopathic azygos vein aneurysm.
AB  - Azygos vein aneurysm is a rare disease. Surgical resection is usually performed
      when it ruptures. To avoid the thromboembolism, procedures that do not touch or
      push the aneurysm are recommended. Herein, we report a case of idiopathic azygos
      vein aneurysm. A 56-year-old woman was admitted to the hospital for right lateral
      chest pain. Chest enhanced multi-detector CT revealed an azygos vein aneurysm in
      the posterior mediastinal space. No thrombus in the aneurysm was detected before
      surgery. Video-assisted thoracic surgery was performed to treat the aneurysm. The
      patient was discharged from the hospital 4 days after surgery. Video-assisted
      thoracic surgery was a good option to treat an azygos vein aneurysm, and an
      enhanced multi-detector CT was useful for performing surgery safely.

PMID- 29322659
TI  - Integrating dose estimation into a decision-making framework for model-based drug
      development.
AB  - Model-informed drug discovery and development offers the promise of more
      efficient clinical development, with increased productivity and reduced cost
      through scientific decision making and risk management. Go/no-go development
      decisions in the pharmaceutical industry are often driven by effect size
      estimates, with the goal of meeting commercially generated target profiles.
      Sufficient efficacy is critical for eventual success, but the decision to advance
      development phase is also dependent on adequate knowledge of appropriate dose and
      dose-response. Doses which are too high or low pose risk of clinical or
      commercial failure. This paper addresses this issue and continues the evolution
      of formal decision frameworks in drug development. Here, we consider the
      integration of both efficacy and dose-response estimation accuracy into the go/no
      go decision process, using a model-based approach. Using prespecified target and
      lower reference values associated with both efficacy and dose accuracy, we build
      a decision framework to more completely characterize development risk. Given the
      limited knowledge of dose response in early development, our approach
      incorporates a set of dose-response models and uses model averaging. The approach
      and its operating characteristics are illustrated through simulation. Finally, we
      demonstrate the decision approach on a post hoc analysis of the phase 2 data for
      naloxegol (a drug approved for opioid-induced constipation).

PMID- 29322660
TI  - Hepatitis C virus infection and risk of osteoporotic fracture: A systematic
      review and meta-analysis.
AB  - BACKGROUND/OBJECTIVES: Hepatitis C virus (HCV) infection is one of the most
      common causes of chronic liver disease. Several epidemiologic studies have
      suggested that patients with HCV infection might have a higher risk of
      osteoporotic fracture. However, the data are inconclusive. This systematic review
      and meta-analysis was conducted with the aims to summarize all available
      evidence. METHODS: A literature search was performed using MEDLINE and EMBASE
      database from inception to June 2016. Studies that reported relative risks, odd
      ratios, or hazard ratios comparing the risk of osteoporotic fracture among HCV
      infected patients versus subjects without HCV infection were included. Pooled
      risk ratio (RR) and 95% confidence interval (CI) were calculated using a random
      effect, generic inverse variance method. RESULTS: Three studies with 362,285
      participants met our eligibility criteria and were included in analysis. We found
      a significantly higher risk of osteoporotic fracture among patients with HCV
      infection with RR of 1.53 (95% CI 1.09 to 2.14). CONCLUSIONS: Our study
      demonstrated an increased risk of osteoporotic fracture among HCV-infected
      patients. Further studies are required to clarify how this risk should be
      addressed in clinical practice.

PMID- 29322661
TI  - Utility of three novel insulin resistance-related lipid indices for predicting
      type 2 diabetes mellitus among people with normal fasting glucose in rural China.
AB  - BACKGROUND: Inexpensive and easily measured indices are needed for the early
      prediction of type 2 diabetes mellitus (T2DM) in rural areas of China. The aim of
      this study was to compare triglyceride glucose (TyG), visceral adiposity (VAI),
      and lipid accumulation product (LAP) with traditional individual measures and
      their ratios for predicting T2DM. METHODS: Data for 11 113 people with baseline
      normal fasting glucose in a rural Chinese cohort were followed for a median of
      6.0 years. Cox proportional hazards regression was used to calculate covariate
      adjusted hazard ratios (aHRs) and 95% confidence intervals (95% CIs) and receiver
      operating characteristic analysis was used to compare the ability of traditional
      measures and TyG, VAI, and LAP at baseline to predict T2DM at follow-up. RESULTS:
      Among individual measures, fasting plasma glucose (FPG) and waist circumference
      (WC) were strongly associated with T2DM. Of all lipid ratios, an elevated
      triglycerides (TG) to high-density lipoprotein cholesterol (HDL-C) ratio was
      associated the most with T2DM. Compared with the first quartiles of TyG, VAI, and
      LAP, their fourth quartiles were associated with T2DM for men (aHR 3.54 [95% CI
      2.08-6.03], 2.89 [1.72-4.87], and 5.02 [2.85-8.85], respectively) and women (6.15
      [3.48-10.85], 4.40 [2.61-7.42], and 6.49 [3.48-12.12], respectively). For
      predicting T2DM risk, TyG, VAI, and LAP were mostly superior to the TG:  HDL-C
      ratio, but did not differ from FPG and WC. CONCLUSIONS: Prediction of T2DM was
      not improved by TyG, VAI, and LAP versus FPG or WC alone. Therefore, TyG, VAI,
      and LAP may not be inexpensive tools for predicting T2DM in rural Chinese people.

PMID- 29322663
TI  - Superficial thrombophlebitis of the legs: still a lot to learn. A rebuttal.

PMID- 29322662
TI  - Reply to more on: the role of thrombin in gliomas.

PMID- 29322664
TI  - Further evidence that fibrillar collagen is unable to promote platelet shape
      change and aggregation in the absence of secondary agonists. Reply to a rebuttal.

PMID- 29322665
TI  - Superficial thrombophlebitis of the legs: still a lot to learn. Reply to a
      rebuttal.

PMID- 29322668
TI  - Discovery of thrombin activatable fibrinolysis inhibitor (TAFI).

PMID- 29322666
TI  - Discovery of thrombin activatable fibrinolysis inhibitor (TAFI).

PMID- 29322669
TI  - Editorial.

PMID- 29322670
TI  - More on: the role of thrombin in gliomas.

PMID- 29322671
TI  - Discovery of thrombin activatable fibrinolysis inhibitor (TAFI).

PMID- 29322672
TI  - Discovery of thrombin activatable fibrinolysis inhibitor (TAFI).

PMID- 29322673
TI  - Attentional bias towards sleep-related stimuli in insomnia disorder: a
      behavioural and ERP study.
AB  - Many studies have used behavioural experiments to show an attentional bias
      towards sleep-related stimuli in people with insomnia disorder. A measurement of
      event-related potential is needed to investigate the cognitive processing
      mechanism of the attentional process. The present study used the emotional Stroop
      paradigm and event-related potentials to measure attentional bias towards sleep
      negative, sleep-positive and sleep-unrelated neutral words. The study comprised
      16 participants with insomnia disorder and 15 participants who were good
      sleepers. Behavioural data indicated that there was a significant interference
      effect of sleep-positive words between the insomnia group and the good sleepers,
      and a marginally significant interference effect from sleep-negative words
      between groups. In the insomnia group, event-related potential data showed that
      sleep-negative words elicited higher amplitudes of P1 and N1 components than did
      sleep-positive and sleep-unrelated words. Our results provide evidence for the
      early cognitive processing of sleep-negative stimuli, which suggests that the
      psychological treatment of insomnia could benefit from addressing early
      hypervigilance towards these stimuli.

PMID- 29322676
TI  - The full-length sequence of the HLA-C allele, HLA-C*03:02:01.
AB  - Confirmed the full-length sequence of HLA-C*03:02:01 by cloning and sequencing in
      a Chinese donor.

PMID- 29322674
TI  - Exposure to West Nile virus and tick-borne encephalitis virus in dogs in Spain.
AB  - In the past decade, the spread of emerging zoonotic flaviviruses (genus
      Flavivirus, family Flaviviridae) has been reported in many regions worldwide,
      representing a threat to both human and animal health. A serosurvey was carried
      out to assess exposure and risk factors associated with antigenically related
      flaviviruses, particularly West Nile virus (WNV), Usutu virus (USUV) and tick
      borne encephalitis virus (TBEV), in dogs in Spain. Flavivirus antibodies were
      detected in 39 of 815 dogs (4.8%; 95% CI: 3.3-6.3) by bELISA. Significantly
      higher seropositivity was observed in hunting dogs compared to pet dogs. Virus
      neutralization tests confirmed WNV-specific and TBEV-specific antibodies in 11
      and 14 bELISA-positive dogs, respectively. This is the first serosurvey of WNV
      and TBEV in dogs in Spain and the first report of TBEV circulation in this
      country. The seropositivity obtained indicates widespread, but not homogeneous,
      distribution of WNV and TBEV in dogs in Spain. In 2013 and 2015, WNV-seropositive
      dogs were detected in those areas of Andalusia where the highest number of WNV
      outbreaks were reported in both horses and humans. Antibodies against TBEV have
      been found in dogs sampled in two different periods and regions in Spain.
      Serosurveillance in dogs could be a complementary way of monitoring the activity
      of emerging flaviviruses in Spain.

PMID- 29322677
TI  - Corrigendum.

PMID- 29322678
TI  - Alteration of IgG4 levels in cerebrospinal fluid in IgG4-related disease.

PMID- 29322679
TI  - Maximising direct observation of procedural skills for learning in the emergency
      department.

PMID- 29322680
TI  - Microbial chemotaxis in the environment: An annotated selection of World Wide Web
      sites relevant to the topics in environmental microbiology.

PMID- 29322681
TI  - Gut microbiome contributes to impairment of immunity in pulmonary tuberculosis
      patients by alteration of butyrate and propionate producers.
AB  - Tuberculosis (TB) is primarily associated with decline in immune health status.
      As gut microbiome (GM) is implicated in the regulation of host immunity and
      metabolism, here we investigate GM alteration in TB patients by 16S rRNA gene and
      whole-genome shotgun sequencing. The study group constituted of patients with
      pulmonary TB and their healthy household contacts as controls (HCs). Significant
      alteration of microbial taxonomic and functional capacity was observed in
      patients with active TB as compared to the HCs. We observed that Prevotella and
      Bifidobacterium abundance were associated with HCs, whereas butyrate and
      propionate-producing bacteria like Faecalibacterium, Roseburia, Eubacterium and
      Phascolarctobacterium were significantly enriched in TB patients. Functional
      analysis showed reduced biosynthesis of vitamins and amino acids in favour of
      enriched metabolism of butyrate and propionate in TB subjects. The TB subjects
      were also investigated during the course of treatment, to analyse the variation
      of GM. Although perturbation in microbial composition was still evident after a
      month's administration of anti-TB drugs, significant changes were observed in
      metagenome gene pool that pointed towards recovery in functional capacity.
      Therefore, the findings from this pilot study suggest that microbial dysbiosis
      may contribute to pathophysiology of TB by enhancing the anti-inflammatory milieu
      in the host.

PMID- 29322682
TI  - Stereotactic ablative radiotherapy versus lobectomy for stage I non-small cell
      lung cancer: A systematic review.
AB  - BACKGROUND: There is debate regarding the use of stereotactic ablative
      radiotherapy (SABR) or surgery for patients with early stage non-small cell lung
      cancer (NSCLC). This meta-analysis compared the clinical efficacy of SABR and
      lobectomy in stage I NSCLC patients. METHODS: An online search identified eight
      eligible articles (including 2 trials and 7 cohort studies) for inclusion. The
      odds ratio (OR) was used as a summary statistic. Overall survival (OS), cause
      specific survival (CSS), and recurrence-free survival (RFS) were selected to
      calculate ORs with 95% confidence intervals (CI). Fixed-effects or random-effects
      models were conducted according to study heterogeneity. RESULTS: There were no
      significant differences between SABR and lobectomy in terms of one-year OS or
      CSS. Significant benefits of surgery were observed in three-year OS (OR 2.11, 95%
      CI 1.55-2.86), three-year CSS (OR 1.94, 95% CI 1.05-3.57), three-year RFS (OR
      1.63, 95% CI 1.12-2.36), and five-year OS (OR 2.40, 95% CI 1.71-3.36). In
      addition, lobectomy demonstrated a beneficial trend in one-year RFS, five-year
      RFS, and CSS. CONCLUSION: Meta-analyses of current evidence suggested that
      lobectomy provides better long-term survival outcomes for stage I NSCLC patients.

PMID- 29322683
TI  - Exploring the research culture of nurses and allied health professionals (AHPs)
      in a research-focused and a non-research-focused healthcare organisation in the
      UK.
AB  - AIMS AND OBJECTIVES: To explore the research culture of nurses and allied health
      professionals (AHPs) in the UK and the influence of a dedicated research strategy
      and funding. It is important to understand the culture in order to effectively
      promote evidence-based patient care. The primary aim of this research was to
      explore the influence of research-focused exposure on the research culture of
      nurses and AHPs in the UK and to identify whether there was a difference in the
      research culture between a research-focused and non-research-focused clinical
      area (City and Riverside Hospitals). BACKGROUND: This is a unique and novel study
      that explored and compared the research culture stance of both AHPs and nurses.
      DESIGN: METHODS: A mixed methods design was used in this study. Tools used
      included the "Research Capacity and Culture tool" as an online survey, three
      focus group discussions and five semi-structured interviews with senior managers.
      Focus groups included research-naive groups from both hospitals and a research
      active group from City Hospital. RESULTS: There were 224 responses received from
      941 surveys with a 24% response rate. Descriptive statistics of the survey
      results indicated that there was a difference (p = .001) in the mean score of the
      research culture between City Hospital (5.35) and Riverside Hospital (3.90), but
      not between nurses and AHPs (p = .12). Qualitative data findings from the
      framework analysis were congruent and supported the survey results. The results
      provided empirical evidence to support a whole-level approach in order to improve
      the research culture. Both findings showed that there may not be any difference
      in the research culture between professional groups. Importantly, new evidence is
      presented to suggest that there were crucial communication issues which were
      hampering the research culture and there was a lack of support at the middle
      management level which needed to be tackled to improve the research culture of
      nurses and AHPs. RELEVANCE TO CLINICAL PRACTICE: The study highlighted the need
      to include a whole-level approach in organisation to improve research culture and
      to include communication within the Cooke's framework if evidence-based practice
      is to influence the quality of patient care.

PMID- 29322684
TI  - Non-surgical periodontal therapy reduces salivary adipocytokines in chronic
      periodontitis patients with and without obesity.
AB  - AIM: The aim of the present study was to assess the effect of scaling and root
      planing (SRP) on periodontal parameters and whole salivary resistin and
      interleukin (IL)-6 levels in chronic periodontitis (CP) patients with and without
      obesity. METHODS: Participants were divided into two groups; group 1 included
      obese and non-obese individuals with CP; and group 2 included obese and non-obese
      individuals without CP. In both groups, bleeding on probing (BOP) and probing
      depth (PD) >=4 mm and whole salivary resistin and IL-6 levels were measured using
      enzyme-linked immunosorbent assay at baseline and 6 months after SRP. The number
      of missing teeth was counted, and marginal bone loss was measured on digital
      panoramic radiographs at baseline and 6 months' postoperatively. RESULTS: BOP was
      significantly higher among obese patients in group 1 than obese (P < .001) and
      non-obese (P < .001) individuals in group 2. At 6 months' follow up, BOP (P <
      .001) and PD >=4 mm (P < .001) were significantly lower among obese and non-obese
      patients in group 1 than their respective baseline values. At 6 months' follow
      up, BOP (P < .001) and PD >=4 mm (P < .001) were significantly higher among obese
      and non-obese individuals in group 1 compared with individuals in group 2.
      CONCLUSION: SRP is effective in reducing periodontal inflammation in CP patients
      with and without obesity. CP seems to be the primary factor that influences
      periodontal status and the expression of resistin and IL-6 levels in obese and
      non-obese patients.

PMID- 29322685
TI  - Feasibility, Safety, and Tolerance of Mesenchymal Stem Cell Therapy for
      Obstructive Chronic Lung Allograft Dysfunction.
AB  - Feasibility, tolerance, and safety of intravenous infusions of allogeneic
      mesenchymal stem cell (MSC) therapy in lung transplant recipients with
      bronchiolitis obliterans syndrome (BOS) are not well established. MSCs were
      manufactured, cryopreserved, transported to our facility, thawed, and infused
      into nine recipients with moderate BOS (average drop in forced expiratory volume
      in 1 second was 56.8% +/- 3.2% from post-transplant peak) who were refractory to
      standard therapy and not candidates for retransplant. Cells were viable and
      sterile prior to infusion. Patients received a single infusion of either 1 (n =
      3), 2 (n = 3), or 4 (n = 3) million MSCs per kg. Patients were medically
      evaluated before; during; and at 24 hours, 1 week, and 1 month after infusion for
      evidence of infusion-related adverse events and tolerance of therapy. Vital
      signs, pulmonary function test results, Borg Dyspnea Index, and routine
      laboratory data were recorded. Vital signs and O2 saturation did not
      significantly change during or up to 2 hours after MSC infusion. There were no
      significant changes in gas exchange variables, pulmonary function test results,
      or laboratory values at 1, 7, and 30 days postinfusion compared with preinfusion
      values. Infusion of MSCs in patients with BOS was feasible, safe, and well
      tolerated and did not produce any significant adverse changes in clinical,
      functional, or laboratory variables during or up to 30 days after infusion.
      Manufacturing, transport, and administration of intravenous, allogeneic bone
      marrow-derived MSCs in doses from 1 to 4 million MSCs per kg is safe in lung
      transplant recipients with BOS. Stem Cells Translational Medicine 2018;7:161-167.

PMID- 29322686
TI  - Human papilloma virus: An etiological and prognostic factor for oral cancer?
AB  - The increasing prevalence of human papilloma virus (HPV)-positive oral tumors can
      be considered an epidemic. Although the incidence of HPV cervical cancer is
      decreasing, the incidence of oral cavity and oropharyngeal cancers associated
      with HPV is increasing. The presence of certain HPV genotypes could be a
      predictor of future oral cancer lesions, although lesions associated with HPV
      could be less aggressive and exhibit a higher survival rate. In the present
      study, we review the most important biologic, clinic, epidemiologic, and
      prognostic factors associated with HPV infection and oral cancer.

PMID- 29322687
TI  - Abnormal fronto-striatal activation as a marker of threshold and subthreshold
      Bulimia Nervosa.
AB  - This study aimed to determine whether functional disturbances in fronto-striatal
      control circuits characterize adolescents with Bulimia Nervosa (BN) spectrum
      eating disorders regardless of clinical severity. FMRI was used to assess
      conflict-related brain activations during performance of a Simon task in two
      samples of adolescents with BN symptoms compared with healthy adolescents. The BN
      samples differed in the severity of their clinical presentation, illness duration
      and age. Multi-voxel pattern analyses (MVPAs) based on machine learning were used
      to determine whether patterns of fronto-striatal activation characterized
      adolescents with BN spectrum disorders regardless of clinical severity, and
      whether accurate classification of less symptomatic adolescents (subthreshold BN;
      SBN) could be achieved based on patterns of activation in adolescents who met
      DSM5 criteria for BN. MVPA classification analyses revealed that both BN and SBN
      adolescents could be accurately discriminated from healthy adolescents based on
      fronto-striatal activation. Notably, the patterns detected in more severely ill
      BN compared with healthy adolescents accurately discriminated less symptomatic
      SBN from healthy adolescents. Deficient activation of fronto-striatal circuits
      can characterize BN early in its course, when clinical presentations are less
      severe, perhaps pointing to circuit-based disturbances as useful biomarker or
      risk factor for the disorder, and a tool for understanding its developmental
      trajectory, as well as the development of early interventions.

PMID- 29322689
TI  - The limits of TEM and beyond - a video vignette.

PMID- 29322688
TI  - Phylodynamics of classical swine fever virus with emphasis on Ecuadorian strains.
AB  - Classic swine fever virus (CSFV) is a Pestivirus from the Flaviviridae family
      that affects pigs worldwide and is endemic in several Latin American countries.
      However, there are still some countries in the region, including Ecuador, for
      which CSFV molecular information is lacking. To better understand the
      epidemiology of CSFV in the Americas, sequences from CSFVs from Ecuador were
      generated and a phylodynamic analysis of the virus was performed. Sequences for
      the full-length glycoprotein E2 gene of twenty field isolates were obtained and,
      along with sequences from strains previously described in the Americas and from
      the most representative strains worldwide, were used to analyse the phylodynamics
      of the virus. Bayesian methods were used to test several molecular clock and
      demographic models. A calibrated ultrametric tree and a Bayesian skyline were
      constructed, and codons associated with positive selection involving immune scape
      were detected. The best model according to Bayes factors was the strict molecular
      clock and Bayesian skyline model, which shows that CSFV has an evolution rate of
      3.2 * 10-4 substitutions per site per year. The model estimates the origin of
      CSFV in the mid-1500s. There is a strong spatial structure for CSFV in the
      Americas, indicating that the virus is moving mainly through neighbouring
      countries. The genetic diversity of CSFV has increased constantly since its
      appearance, with a slight decrease in mid-twentieth century, which coincides,
      with eradication campaigns in North America. Even though there is no evidence of
      strong directional evolution of the E2 gene in CSFV, codons 713, 761, 762 and 975
      appear to be selected positively and could be related to virulence or
      pathogenesis. These results reveal how CSFV has spread and evolved since it first
      appeared in the Americas and provide important information for attaining the goal
      of eradication of this virus in Latin America.

PMID- 29322690
TI  - Microbially mediated aluminosilicate formation in acidic anaerobic environments:
      A cell-scale chemical perspective.
AB  - Through the use of scanning transmission electron microscopy (STEM) combined with
      other complementary techniques (SEM, cryo-TEM, HRTEM, and EELS), we have studied
      the interaction of microorganisms inhabiting deep anoxic waters of acidic pit
      lakes with dissolved aluminum, silica, sulfate, and ferrous iron. These elements
      were close to saturation (Al, SiO2 ) or present at very high concentrations (0.12
      m Fe(II), 0.12-0.22 m SO42- ) in the studied systems. The anaerobic conditions of
      these environments allowed investigation of geomicrobial interactions that are
      difficult to see in oxidized, Fe(III)-rich environments. Detailed chemical maps
      and through-cell line scans suggest both extra- and intracellular accumulation of
      Al, Si, S, and Fe(II) in rod-like cells and other structures (e.g., spherical
      particles and bacteriomorphs) of probable microbial origin. The bacterial rods
      showed external nanometric coatings of adsorbed Fe(II) and Al on the cell surface
      and cell interiors with significant presence of Al, Si, and S. These microbial
      cells coexist with spherical particles showing similar configuration (Fe(II)
      external coatings and [Al, Si, S]-rich cores). The Al:Si and Al:S ratios and the
      good Al-Si correlation in the cell interiors suggest the concurrent formation of
      two amorphous phases, namely a proto-aluminosilicate with imogolite-like
      composition and proto-hydrobasaluminite. In both cases, the mineralization
      appears to comprise two stages: a first stage of aluminosilicate and Al
      hydroxysulfate precipitation within the cell or around cellular exudates, and a
      second stage of SO42- and Fe(II) adsorption on surface sites existing on the
      mineral phases in the case of (SO42- ) or on presumed organic molecules [in the
      case of Fe(II)]. These microbially related solids could have been formed by
      permineralization and mineral replacement of senescent microbial cells. However,
      these features could also denote biomineralization by active bacterial cells as a
      detoxification mechanism, a possibility which should be further explored. We
      discuss the significance of the observed Al/microbe and Si/microbe interactions
      and the implications for clay mineral formation at low pH.

PMID- 29322692
TI  - Patient characteristics associated with treatment response in patients receiving
      salvianolate injection for stable angina.
AB  - OBJECTIVE: To explore patient characteristics associated with treatment response
      in patients receiving salvianolate injection for stable angina. METHODS: An
      analysis was conducted of data from a multicenter, phase IV clinical trial
      undertaken in China that enrolled 2150 patients hospitalized for stable angina
      from 50 hospitals. The treatment outcomes were changes of angina severity and
      nitroglycerin use between baseline and the last day of treatment. We used
      logistic regression models to explore patient characteristics associated with the
      treatment response. RESULTS: Patients who were overweight or obese (ORa 1.20, 95%
      CI 1.01 to 1.44), present with hypertension (ORa 1.23, 95% CI 1.01 to 1.49),
      experienced with 3 or more episodes of angina per week (ORa 1.77, 95% CI 1.44 to
      2.17), or concomitantly using antiplatelet agents (ORa 1.44, 95% CI 1.17 to 1.78)
      were associated with better treatment response defined with the change of angina
      severity. Those of overweight or obesity (ORa 1.57, 95% CI 1.17 to 2.12) or
      concomitantly using calcium antagonists (ORa 2.38, 95% CI 1.39 to 4.08) fared
      better treatment response according to discontinuation or reduction of
      nitroglycerin use. CONCLUSIONS: Patients diagnosed with stable angina and
      receiving salvianolate injection might fare better treatment response if they
      were overweight or obese, experienced with hypertension, three or more episodes
      of angina per week, or concomitantly using antiplatelet agents and calcium
      antagonists.

PMID- 29322691
TI  - Raspberry Supplementation Improves Insulin Signaling and Promotes Brown-Like
      Adipocyte Development in White Adipose Tissue of Obese Mice.
AB  - SCOPE: Excessive lipid accumulation in white adipose tissue (WAT) leads to
      chronic inflammation and metabolic dysfunction. Raspberry (RB) contains high
      amount of polyphenols and dietary fibers. The objective of the study is to
      evaluate the effects of RB supplementation on WAT morphology, inflammation, and
      insulin signaling in high fat diet (HFD)-induced obese mice, and further explore
      the underlying mechanisms. METHODS AND RESULTS: C57BL/6J mice are fed with a
      control diet or a HFD supplemented with 0 or 5% freeze dried RB for 12 weeks. RB
      supplementation decreases WAT hypertrophy induced by HFD and suppresses pro
      inflammatory cytokines expression and macrophage infiltration in WAT. Meanwhile,
      RB addition improves insulin sensitivity of HFD-mice. Additionally, RB
      supplementation drives the browning of WAT (beige adipogenesis), which is
      associated with elevated PGC-1alpha and FNDC5/irisin contents. Consistently, the
      content of beige adipocyte markers including UCP1, PRDM16, Cytochrome C, Cidea,
      and Elvol3 is enhanced in HFD-mice, which are correlated with increased AMPK
      phosphorylation and Sirt1 protein contents. CONCLUSION: Dietary RB attenuated
      adipocyte hypertrophy and inflammation of WAT in HFD-mice and improves insulin
      sensitivity and beige adipogenesis, which is associated with increased
      FNDC5/irisin content and activation of AMPK/Sirt1 pathway. RB supplementation
      provides a promising strategy to prevent diet-induced obesity.

PMID- 29322693
TI  - See one, do one, teach one: Is it enough? No.

PMID- 29322695
TI  - Bioresorbable Scaffolds in Coronary Intervention: Unmet Needs and Evolution.
AB  - Bioresorbable scaffolds (BRS) represent a novel paradigm in the 40-year history
      of interventional cardiology. Restoration of cyclic pulsatility and physiologic
      vasomotion, adaptive vascular remodeling, plaque regression, and removal of the
      trigger for late adverse events are expected BRS benefits over current metallic
      drug-eluting stents. However, first-generation BRS devices have significant
      manufacturing limitations and rely on optimal implantation technique to avoid
      experiencing an excess of clinical events. There are currently at least 22 BRS
      devices in different stages of development, including many trials of device
      iterations with thinner (<150 MUm) struts than first-generation BRS. This article
      reviews the outcomes of commercially available and potentially upcoming BRS,
      focusing on the most recent stages of clinical development and future directions
      for each scaffold type.

PMID- 29322696
TI  - The J-curve between Diastolic Blood Pressure and Risk of All-cause and
      Cardiovascular Death.
AB  - BACKGROUND AND OBJECTIVES: The J-curve phenomenon between diastolic blood
      pressure (DBP) and mortality has been reported repeatedly in treated patients.
      However, the baseline risk of low DBP has not been fully explored. This study was
      to examine the relationship between DBP and risk of mortality from all-cause,
      atherosclerotic vascular diseases (ASCVD), and ischemic heart disease (IHD) using
      a prospective cohort of general population. METHODS: We analyzed 1,234,435
      participants of the Korean Cancer Prevention Study cohort (789,255 men, 30-95
      years of age) who had a medical evaluation from 1992 to 1995 using Cox
      proportional hazards models. RESULTS: A total of 22.5 million person-years were
      followed up (mean age 46.6 years, deaths 193,903 cases). The hazard ratios of
      mortality from all-cause and ASCVD, among those with DBP <60 mmHg compared to 70
      79 mmHg were 1.23 (95% confidence interval [CI], 1.16-1.30) and 1.37 (95% CI,
      1.20-1.57), respectively, after adjustment for multivariable including systolic
      blood pressure. Increased risks of all-cause death in the lowest DBP category
      group were maintained in men or women, 30-59 or >=60 years of age, smoker or non
      smoker and diabetes mellitus (DM) or non-DM subgroups. The risk in DBP 60-69 mmHg
      groups increased in several subgroups. However, the risk for ASCVD death in 30-59
      years and DM group, and risk for IHD death in most subgroups except for elderly
      (>=60 years) decreased. CONCLUSION: A J-curve relationship between low DBP and
      all-cause death was found consistently. The baseline risk in the general
      population may be considered for risk assessment, particularly in case of
      interventions that lower DBP below 60 mmHg.

PMID- 29322697
TI  - J-curve Phenomenon Might Be Inherent: How to Know If It Is Treatment Induced?

PMID- 29322698
TI  - Timing and Indications for Aortic Valve Surgery in Korean Bicuspid Aortic Valve
      Patients.

PMID- 29322699
TI  - Contrast-induced Acute Kidney Injury and Inflammation.

PMID- 29322700
TI  - Factors Predicting Resistance to Intravenous Immunoglobulin and Coronary
      Complications in Kawasaki Disease: IVIG Resistance in Kawasaki Disease.

PMID- 29322701
TI  - Can Pre-analytical Mistake Bearing Irisin Concentrations Be an Indicator of
      Coronary Artery Disease?

PMID- 29322702
TI  - Factors Affecting Outcome and the Role of Plasmapheresis in Guillain-Barre
      Syndrome.

PMID- 29322703
TI  - Impact of Electrophysiological and Clinical Variants, and Timing of
      Plasmapheresis on Outcome of Guillain-Barre Syndrome.
AB  - Introduction: Guillain-Barre syndrome (GBS) is an autoimmune polyneuropathy
      causing acute flaccid paralysis and it is known to improve with plasmapheresis.
      Objective: To study effects of electrophysiological type of GBS, clinical variant
      of GBS and time taken for initiation of plasmapheresis on outcome of disease.
      Methods: 50 consecutive patients of GBS attending tertiary care hospital
      underwent clinical examination and electrophysiological studies. Disability grade
      was calculated and patients were observed for full functional recovery for 6
      months. Results: In this study, patients in whom plasmapheresis was started
      within 7 days (n=39) were observed to have significantly better improvement in
      terms of smaller peak disability and rapid functional recovery compared to those
      in whom plasmapheresis was started after 7 days (n=11). (p<0.002). Demyelinating
      pattern on electrophysiology was observed to have better outcome in terms of all
      parameters compared to axonal. AIDP variant was observed to have best outcome and
      AMSAN variant was associated with worst outcome. Conclusions: Rapid institution
      of plasmapheresis is the most important outcome determining factor. Irrespective
      of the variant specific comorbidity, early plasmapheresis improves outcome in all
      parameters.

PMID- 29322704
TI  - Evaluation of Cerebral Venous Thrombosis by CT, MRI and MR Venography.
AB  - Objective: To study and compare cerebral parenchymal changes and sinuses
      involvement in CT with MRI and MRV in Cerebral Venous Thrombosis patients.
      Method: This study was carried out in the Department of Radiodiagnosis, JLN
      Hospital and Research Center, Bhilai, Chhattisgarh from October 2012 to Nov 2014
      and includes fifty patients of all age groups presenting with clinical symptoms
      of CVT, admitted in Neurology, Neurosurgery, Medicine, Pediatric, obstetric and
      Gynecology wards. CT, MRI and MRV findings were noted and statistical analysis
      was done using SPSS (Statistical package for Social science) 17.0 software.
      Categorical variables are expressed as frequencies and percentages. Sensitivity,
      Specificity, PPV and NPV of CT were calculated with respect to MRI in the
      diagnosis of cerebral venous thrombosis and associated brain parenchymal changes.
      Result: Out of fifty cases of cerebral venous thrombosis, thirty-one were females
      and nineteen were males. Age range was newborn to seventy-one years with female
      predominance in young age. Majority of the patients presented with headache (78%)
      followed by seizures (32%). Out of the total 50 cases, superior sagittal sinus
      were involved in 24 cases, left transverse sinus in 22 cases, right transverse in
      12 cases, left sigmoid in 20 cases, right sigmoid in 13 cases, left internal
      jugular vein in 12 cases, right internal jugular vein in 7cases, straight sinus
      in 5cases, superficial cortical veins in 6 cases, vein of Galen in 3 cases and
      internal cerebral veins in 2 cases. Cerebral parenchymal changes were associated
      with thrombosis in 26 patients, hemorrhagic infarct in 13 cases, only hemorrhage
      in 4 cases and only infarct in 5 cases. CT scan was able to diagnose sinus
      abnormality in 36% and parenchymal abnormality in 42% of cases as compare to 100%
      and 52% in MRI. Conclusion: In the emergency setting CT scan plays an important
      role in evaluating patients clinically suspected CVT, whereas MRI combine with MR
      Venography is the best imaging technique for diagnosis of CVT in patients with
      equivocal findings on CT.

PMID- 29322705
TI  - A Comparative Study of In-Hospital Outcome of Patients with ST-Segment Elevation
      Myocardial Infarction with and Without Diabetes Mellitus, after Thrombolytic
      Therapy; In Government Hospital of Rajkot, Gujarat, India.
AB  - Background: Diabetes mellitus is considered as a major health problem and an
      epidemic throughout the world. The mortality of patients with diabetes is almost
      twice that of non-diabetic. The outcome of in-hospital patients with myocardial
      infarction with and without diabetes after thrombolytic therapy is presented
      here. Aim: To compare the outcome of patients with myocardial infarction after
      thrombolysis in diabetics and non-diabetics in government hospital of Rajkot,
      India. Methods: A retrospective, observational study was carried out between the
      period of March-2014 to April-2015. Patients who presented with acute myocardial
      infarction having ST-elevation as MI picture, were admitted to the emergency room
      of medicine department. All these patients were treated with streptokinase as a
      thrombolytic agent. Baseline ECG was taken on admission and the one after 60
      minutes of thrombolysis. The study group involved two types: (i) diabetic (ii)
      nondiabetics. Results: A total of 395 patients were included in the study. Out of
      them around 104 were females and 291 were males. ST-segment resolution in non
      diabetic patients was found in 180 patients out of 186 and in diabetics it was
      found in 174 patients out of 208. Complications related to post fibrinolytic
      therapy was more prevalent in diabetics 148 patients (71.15%) as compared to
      those in non-diabetics 47 patients (25.26%). Mortality was observed only with
      diabetics (23.52%) as compared to no mortality in non-diabetics. Conclusion:
      Overall, morbidity and mortality of diabetic patients with Acute Myocardial
      Infarction was found to be greater as compared to non-diabetics; post
      thrombolysis.

PMID- 29322706
TI  - Osteoporosis in Postmenopausal Females with Primary Knee Osteoarthritis in a
      Vitamin D Deficient Population.
AB  - Aim and Objective: To find prevalence of osteoporosis (OP) in postmenopausal
      females with primary knee osteoarthritis (OA) in India, where there is widespread
      Vitamin D deficiency (VDD). Material and Methods: 75 postmenopausal women (PMW)
      fulfilling ACR criteria for Knee OA between 40 - 60 years of age, having OA grade
      2 or more as per Kellgren Lawrence grade on anterior- posterior radiograph of the
      right knee were enrolled. 34 PMW of the same age with normal right knee
      radiograph were taken as controls. Bone mineral density (BMD) of lumber spine (L1
      L4), total hip and left forearm was performed using DXA in all patients and
      controls. The results were expressed in absolute values (g/cm2) and as per WHO
      criteria - Osteoporosis: T score < -2.5, Osteopenia: T score between -1 and -2.5.
      Vitamin D Level was done by ELISA. Results: Body mass index (BMI) of patients was
      significantly higher than controls (p 0.006). There was no difference in BMD
      between patients and controls at any site. Forty percent patients and 53%
      controls had osteopenia (p ns), while 34.6% patients and 41.1% controls had
      osteoporosis at any site (p ns). When this comparison was made at each site there
      was no difference between patients and controls. Conclusion: Prevalence of
      osteoporosis in PMW with primary knee OA is similar to that in general
      population.

PMID- 29322707
TI  - Knowledge, Attitudes, Beliefs and Practices of Physicians Regarding Idiopathic
      Pulmonary Fibrosis and the Impact of a Continuing Medical Education Program.
AB  - Background: Significant deficiencies have been identified previously in the
      knowledge of physicians regarding the current diagnosis and management of
      idiopathic pulmonary fibrosis (IPF). Whether a continuing medical education (CME)
      program helps in overcoming these deficiencies has never been studied. Methods:
      This was a questionnaire-based study performed to assess the knowledge,
      attitudes, beliefs and practices of physicians regarding IPF before and after
      attending a CME program at a tertiary care teaching Institute in northern India.
      A questionnaire comprising of 18 questions on knowledge, attitudes, beliefs and
      practices regarding IPF (designed by Delphi method) was self-administered by the
      participants prior to (pretest) and after (posttest) attending the program. The
      pretest and posttest knowledge and belief scores (maximum achievable score 17)
      were compared. Results: Of the total 98 physicians who agreed to participate, 84
      completed the pretest questionnaire. The mean (SD) total score for knowledge and
      beliefs questionnaire was 10.7 (3.5). The mean (SD) pretest and posttest scores
      of 52 subjects, who completed both the questionnaires were 10.3 (3.4) and 11.1
      (2.9) respectively with a mean increase of 0.8 (p=0.048). The proportion of
      participants who scored >50% increased (p=0.046) from 41 (78.8%) to 48 (92.3%)
      between the pretest and posttest questionnaires. Only 54.8% and 47.6% of the
      participants responded correctly to the questions on CT features and drugs useful
      for IPF, respectively. Conclusions: Significant deficiencies were noted in the
      knowledge of IPF among a small group of physicians attending a CME. A CME program
      with didactic lectures helps improving the knowledge only marginally.

PMID- 29322708
TI  - High Prevalence of Obstructive Sleep Apnea among People with Type 2 Diabetes
      Mellitus in a Tertiary Care Center.
AB  - Purpose: Untreated obstructive sleep apnea (OSA) is a risk factor for
      hypertension and cardiac events, and is associated with increased mortality.
      Recent studies indicate that majority of people with type 2 diabetes also has
      OSA. The aim of this study was to assess the prevalence and severity of OSA and
      risk factors contributing to it among people with chronic and severe type 2
      diabetes. Methods: A total of 203 people with type 2 diabetes (mean age: 54+/-8
      years, 145 males, 58 females, HbA1c >=7% [53mmol/mol]) attending a diabetes
      specialty hospital were included in the study; all were subjected to
      comprehensive diabetic evaluation and Apnea Hypopnea Index (AHI) was used to
      evaluate OSA. Results: 23.65% of the study subjects had OSA (AHI >=15). OSA was
      more prevalent among men compared to women. BMI, was significantly higher among
      subjects with OSA (P=0.01). People with OSA had higher percentage of diabetic
      complications such as cardiovascular disease (CVD), retinopathy and neuropathy.
      Hypertension was identified as independent predictors of OSA. Conclusions:
      Prevalence of OSA was higher in this study compared to Indian studies hitherto.
      Since OSA is treatable, people with diabetes should be screened for this
      condition to reduce their CVD risk.

PMID- 29322709
TI  - Study of Association of Thyroid Hormone in Pre-Eclampsia and Normal Pregnancy.
AB  - Aim: The aim of the study was to assess association of thyroid hormone in
      preeclampsia and normal pregnancy. Material and Method: This was a hospital based
      observational case control study. Total 100 women were included, out of them 50
      normal pregnant women in control group and 50 pre-eclamptic women in case group
      were included. Result: In this study no significant difference was found in FT3
      (p value 0.085) and FT4 (p value 0.065) in control and case group. TSH and Anti
      TPO levels in control and case group were statistically significant (p value
      <0.001 and <0.000). Conclusion: We observed that thyroid hormones (TSH and Anti
      TPO) have statistically significant relation in pre-eclamptic women.

PMID- 29322710
TI  - Etiology and Outcomes of Lower Limb Ulcers in Non-Diabetic Patients, An
      Experience from Government Hospital in Western India.
AB  - Aim: To study the Etiology and Outcomes of Lower Extremity Ulcer in Non- Diabetic
      Patients. Method: A total number of 40 patients were collected from Rheumatology
      services (Department of Medicine), Venous Clinic (Department of Surgery) and
      Dermatology Clinic (Department of Dermatology) of a tertiary care hospital in
      Mumbai over a period of 48 months from January 2013 to December 2016. The study
      included serial recruitment of lower limb ulcer fulfilling inclusion criteria.
      Results: Patients with lower limb ulcers presented with a wide range of
      pathology. Ulcers due to Vasculitis was the most common etiology (40%) and
      affected females predominantly (12/16). Venous ulcers were the second most common
      etiology and predominantly affected men (8/10). Conclusion: It is important to
      consider differential diagnosis of Vasculitic ulcer in chronic non healing ulcers
      as they show rapid response to treatment with immunosuppressant. If such ulcers
      are not promptly diagnosed and treated properly, systemic vasculitis can cause
      end organ damage or even endanger patient life.

PMID- 29322711
TI  - High Prevalence of Hypovitaminosis D in Patients Presenting with Proximal Muscle
      Weakness: A Sub-Himalayan Study.
AB  - Background: Hypovitaminosis D has emerged as a major public health problem and 25
      50% of patients encountered in clinical practice are deficient in vitamin D. This
      study was conducted to estimate the prevalence of hypovitaminosis D among
      patients presenting with proximal muscle weakness. Study Design: It was a cross
      sectional study done on patients >=18 years presenting in outdoor clinic from May
      2008 to April 2013, with difficulty in standing and going up stairs/ diffuse
      musculoskeletal pains. Proximal muscle weakness due to other causes were excluded
      through investigations and those taking steroids and/or indigenous drugs were
      also excluded. Vitamin D levels measured by radioimmunoassay (RIA) in all
      eligible patients and individuals included in the study were those with
      hypovitaminosis D (<30ng/dl) and proximal muscle weakness. Patients reassessed
      after supplementation with vitamin D at 2 and 6 months. Results: 99 patients with
      hypovitaminosis D associated proximal myopathy included in study. Of these 55
      (55.55%) were males and 44 (44.44%) were females. Age ranged from 22 to 82 years
      with a mean of 52.84 +/- 12.6 years. Of 99 patients, 55 (55.55%) were from the
      rural area and 44 (44.44%) from urban area. Mean duration of symptoms was 22.7
      months (range 6-60 months). The level of 25(OH) Vitamin D ranged from 2.0 ng/dl
      to 35.7 ng/dl with the mean level of 13.18 +/- 5.80 ng/dl (males = 12.76+/-
      4.85ng/dl and females = 13.60+/-6.70ng/dl). Hypovitaminosis D was present in
      98.98%. A direct relationship was found between the vitamin D levels (<10 ng/dl)
      and severity of weakness. Of 83 patients, who reported at the end of two and six
      months of treatment, 71 (85.54%) patients were able to stand-up from squatting
      position. Conclusion: Muscle weakness is common among vitamin-D deficient
      individuals. Our study indicates that more focus should be on muscle symptoms in
      at risk population groups. The vitamin D deficiency related myopathy should not
      be missed due to its potential reversibility with vitamin D supplementation.

PMID- 29322712
TI  - A Cross-sectional Study of Cardiovascular Involvement in Systemic Lupus
      Erythematosus in an Urban Indian Tertiary Care Centre with Emphasis on 2-D
      Echocardiography.
AB  - Background: Cardiovascular manifestations are responsible for considerable
      morbidity and mortality in patients with SLE. A wide range of manifestations due
      to active lupus, like pericarditis, valvular affection, myocarditis, and less
      commonly pulmonary hypertension, are described. This study was undertaken to
      study cardiovascular manifestations in SLE, with a focus on echocardiography
      findings, in an urban Indian setting. Methodology: Fifty consecutive cases of SLE
      following up in the Rheumatology Clinic of TNMC and BYL Nair Charitable hospital,
      an Indian tertiary care hospital were studied. They were subjected to an
      echocardiographic examination if not already done. Detailed history, examination,
      study of past medical records and investigations were carried out, especially
      related to cardiovascular system. Treatment details, flares, other systemic
      involvement were noted. Serial echocardiography if done previously were noted
      down. The data was analysed using descriptive statistics. Results: An
      echocardiographic abnormality was noted in 25 (50%) of the 50 subjects. Pulmonary
      hypertension in 21(42%); valvular abnormalities in 16 (32 %); pericardial
      effusion in 9 (18%) and diastolic dysfunction in 6(12%) were the echocardiography
      findings. Six out of the 7 cases with moderately to severe pulmonary hypertension
      seemed to be responding to immunosuppressive therapy clinically as well as on
      echocardiography; 1 did not respond. At least 1 traditional risk factor for
      atherosclerosis was present in 58% of cases. Conclusions: Screening
      echocardiography may be recommended, especially at presentation, during SLE
      flare, or in the presence of cardiac symptoms. Moderate to severe pulmonary
      hypertension can develop any time in the course of the disease. It may be
      responsive to immunosuppression. Further detailed studies including multiple
      echocardiographic parameters and right heart catheterisation need to be
      undertaken to study the responsiveness of pulmonary hypertension to
      immunosuppresssive therapy.

PMID- 29322713
TI  - Communication Adaptations for a Diverse International Patient Population.
AB  - We live in an age of hyper connectivity, people from around the world are looking
      outside their own national borders to receive medical care. As more people are
      learning about the quality that the elite Indian hospitals provide at a
      competitive, and often more affordable, price compared to other institutions
      around the world, they are becoming increasingly interested in receiving their
      medical care in Indian hospitals. It is for this exact reason that it is very
      important to learn the importance of communicating effectively with people from a
      diverse background. Over the next decade, the number of international patients
      that Indian hospitals will provide care for is set to dramatically increase. In
      this new age of medicine in India, it is imperative that doctors are adequately
      equipped with the communication skills to appropriately connect with patients
      coming from very different cultural backgrounds. The interaction with an
      international patient can be tremendously deepened through effective
      communication that adheres to the cultural beliefs of the patient. In this
      article, we detail how to effectively communicate with people from different
      backgrounds. We explore how to speak with patients and connect on a deeper level
      and respect the cultural differences that exist. We will also discuss how to
      avoid offending your patients or miscommunicating your plans to them. Overall,
      improved awareness of cultural differences will ensure higher patient
      satisfaction as well as an improved doctor patient interaction.

PMID- 29322714
TI  - Novel Regimens in the Treatment of Paracetamol (Acetaminophen) Poisoning.

PMID- 29322715
TI  - Heart Failure and the Iron Deficiency.
AB  - Iron deficiency anemia is a significant problem worldwide and more so in
      developing countries, like India. The prevention and treatment of iron deficiency
      is a major public health goal in India It is now well recognized that iron
      deficiency has detrimental effects in patients with coronary artery disease,
      heart failure, and pulmonary hypertension, and possibly in patients undergoing
      cardiac surgery. Around one-third of all patients with HF, and around one-half of
      patients with pulmonary hypertension, are affected by iron deficiency.1.

PMID- 29322716
TI  - Common Statistical Errors and how to Avoid them.

PMID- 29322717
TI  - Giant Intraparanchymal Neurocysticercosis.

PMID- 29322718
TI  - Crochetage Sign.

PMID- 29322719
TI  - Life-threatening Medical Complications Due to Ovarian Hyperstimulation Syndrome:
      A Hidden Etiology.
AB  - Ovarian hyperstimulation syndrome is usually an iatrogenic complication in women
      taking ovulation induction medications during assisted reproduction. We hereby
      report the case of a 25 years old female who presented with hypertension,
      polyserositis with tense ascites and large cystic ovaries. She developed sigmoid
      and transverse sinus thrombosis. She had undergone a clandestine ovulation
      induction therapy as a commercial ovum donor. She fitted in severe category of
      ovarian hyperstimulation syndrome.

PMID- 29322720
TI  - Invasive Aspergillus Pseudomembranous and Obstructive Tracheo-bronchitis in an
      Immuno-competent Patient.
AB  - A 19 year female, presented with life threatening haemoptysis and cough with
      minimum expectoration for 3 months. Bronchoscopy showed multiple nodules in
      airway. The direct microscopy and culture of sputum revealed fungal elements and
      Aspergillus flavus respectively. Serum Galactomannan was positive. Thus diagnosis
      of invasive aspergillus tracheo-bronchitis made. She responded to voriconazole.
      Aspergillus tracheo-bronchitis is a rare form of invasive pulmonary aspergillosis
      in immuno-competent host. Aspergillus spp in respiratory samples should not be
      routinely discarded as colonization.

PMID- 29322721
TI  - Mandibular AV Malformation: A Rare Cause of Massive Bleeding from Mouth Managed
      with Multiple Vessel Embolization.
AB  - An arteriovenous malformation (AVM) is a site of abnormal connectivity between
      arteries and veins. Arteriovenous malformations of jaw are extremely rare
      conditions that can result in disastrous complications, if handled carelessly.
      Although various treatment modalities have been advocated in the literature,
      there seems to be no complete consensus on a suitable treatment in these cases.
      We describe a case of mandibular AVM, who presented with massive bleeding from
      mouth and each time, embolization of one vessel was done, it recruited new
      vessel.

PMID- 29322722
TI  - Unusual Presentation of Injection Site Adverse Effect.
AB  - Insulin is an integral part of Type 1 diabetes management. Patient education is
      of utmost importance to ensure proper injection technique for getting appropriate
      glycaemic control and to avoid injection site adverse effects. Commonest
      injection site adverse effect is lipodystrophy.1 We present a case where
      incorrect injection technique led to an unusual presentation of injection site
      adverse effect, which is resolving after correction of the injection technique.

PMID- 29322724
TI  - Medical Symbols: Part-1.

PMID- 29322723
TI  - Thyrotoxic Channelopathies.
AB  - Thyrotoxic periodic paralysis (TPP), a disorder most commonly seen in Asian men,
      is characterized by abrupt onset of hypokalemia and paralysis. The condition
      primarily affects the lower extremities and is secondary to thyrotoxicosis. Early
      recognition of TPP is vital to initiating appropriate treatment and to avoiding
      the risk of rebound hyperkalemia that may occur if high-dose potassium
      replacement is given. Here we present a case of 31 year old male with thyrotoxic
      periodic paralysis with diagnostic and therapeutic approach.

PMID- 29322725
TI  - Painless Krait Bite in a Sleeping Victim: Delayed Diagnosis and High Mortality.

PMID- 29322726
TI  - Thrombocytopenia as Harbinger of Graves' Disease: A Rare Presentation.

PMID- 29322727
TI  - [Demographic Aspects of Population Aging in Saint-Petersburg at the End of XX-the
      beginning of XXI Century. Part II. Prospective Aging Measures.]
AB  - The paper is the second part of the series of two articles on demographic aspects
      of population aging in Saint-Petersburg in 1990-2010/2014 compared to the
      situation in the Russian Federation as a whole. In the first part, the situation
      with population aging in Saint-Petersburg and Russia was considered based on
      traditional aging measures. In the second part, a number of prospective aging
      measures that take account of remaining life expectancy are studied, such as
      Prop. RLE 15 (proportion of population with remaining life expectancy 15 years or
      less), POADR (prospective old-age dependency ratio), population average remaining
      years of life (PARIL). Prospective aging indicators are compared with their
      traditional analogues. Gender imbalance of prospective aging measures has been
      considered.

PMID- 29322728
TI  - [Population aging in Kazakhstan. 2. Public policy responses.]
AB  - This article consists of the concluding sections of the review devoted to the
      issues of population aging in the Republic of Kazakhstan. The presented material
      is intended to substantiate strategic approaches for addressing the evolving
      process of population aging in Kazakhstan.

PMID- 29322729
TI  - [Age-related changes in the content of serine-arginine protein kinase 1 (SRPK1)
      in human dermis.]
AB  - The aim of our work was to examine content of serine-arginine protein kinase 1
      (SRPK1) in human dermis at different ages (from 20 weeks of pregnancy to 85 years
      old). SRPK1, proliferating cells nuclear antigen (PCNA ), endothelial marker CD31
      were detected in sections of the skin by indirect immunohistochemistry. Results
      showed, that content of SRPK1 in dermal fibroblasts was increased form antenatal
      period to 20 years of life followed by a decrease until 61-85 years period. SRPK1
      content in dermal blood vessels is slowly gradually increased from antenatal
      period to 61-85 age interval. The number of fibroblasts and their proliferative
      activity, the number of CD31 positive blood vessels in dermis were decreased from
      antenatal period to 61-85 years period of life. Age-dependent decrease in SRPK1
      in dermal fibroblasts from 20 years is associated with a reduction in the number
      and proliferative activity of fibroblasts. Age-related increase in SRPK1 content
      in dermal blood vessels is associated with a diminishing of the number of blood
      vessels. Hence, it can be supposed that SRPK1 has different actions on
      proliferation of differ components of dermis during aging.

PMID- 29322730
TI  - [Age-related changes of water transport by corneal endothelial cells in rats.]
AB  - Senescence-associated alterations in structure and function of cornea make it
      more sensitive to traumas and disease. Trauma of cornea leads to edema and vision
      impairment and only corneal transplantation remains the effective for vision
      correction. Role of aquaporins for cornea endothelium function, as well as age
      related changes of their activity, are not entirely understood. Herein, we
      studied changes with age the water permeability (Pf) of the plasma membranes of
      the corneal endothelial cells and the level of expression in them of the mRNA
      genes of the water channels of the aquaporins AQP1 and AQP3 in Wistar and
      senescence-accelerated OXYS rats. From the age of 3 to 18 months, Pf in Wistar
      rats increased, in OXYS - decreased and was twice lower than in Wistar rats. The
      expression of aqp1 mRNA (studied by RT-PCR) in the endothelium was the same in
      Wistar and OXYS rats at the age of 3 months. By the age of 18 months, it
      increased only in Wistar rats and became twice higher than in OXYS rats. The
      expression of aqp3 mRNA in the endothelium of 3-month-old OXYS rats was half that
      of Wistar rats and did not change with age, while in Wistar rats it decreased and
      at 18 months was 4 times lower than in 3 months. We supposed that increased water
      permeability of endothelial cells in Wistar rats is adaptive and compensates for
      the decrease in endothelial cell density with age, while the accelerated aging of
      OXYS rats abolishes this compensation.

PMID- 29322731
TI  - [Age changes in connective tissue structures of the stomach.]
AB  - The study of paravasal connective tissue of the stomach was carried out on the
      preparations of 80 men corpses of three age groups: the first period of adulthood
      (n=20), the elderly (n=30) and senile (n=30) ages. With the help of standard
      histological and histochemical methods, the features of the age-related
      variability of the fiber composition were established; the level of apoptosis and
      proliferation in fibroblasts has been investigated with the help of
      immunohistochemical methods. The regularities of the structural organization of
      the paravasal connective tissue of the stomach during the period of biological
      stability (the first period of adulthood), as well as its age transformations at
      the stages of postnatal ontogeny (in the older age groups), were revealed.

PMID- 29322732
TI  - [Functional cumulation of influence of vascular peptide bioregulator on
      microcirculation in the brain cortex of spontaneously hypertensive rats.]
AB  - We investigated the influence of vascular peptide bioregulator on
      microcirculation in the brain cortex of spontaneously hypertensive rats of
      different ages and figured out whether there is functional cumulation during two
      time application of the drug "Slavinorm" by above-mentioned animals. It was shown
      that a single course treatment with vascular peptide bioregulator had increased
      the density of microvascular network of the pia mater in young animals ca. 1,2
      fold and had not affected the perfusion and oxygen saturation of sensorimotor
      cortex. The second course treatment with "Slavinorm" was provided in a 6 months.
      Functional cumulation was revealed in 12 month-aged rats which had 2 course
      treatments with vascular peptide bioregulation: the density of microvascular
      network of the pia mater was increased ca. 1,6-fold; level of perfusion was
      increased ca. 15% in comparison with intact animals of the same age. These
      animals were more tolerant to cerebral vasospasm (the application of
      vasoconstrictor on the surface of the brain): the highest level of tissue oxygen
      saturation was remained at fairly constant perfusion in comparison with other
      animals.

PMID- 29322733
TI  - [Blue death of nematodes.]
AB  - This paper shows that the aging and death of nematodes, accompanied by the
      ignition of a blue glow under fluorescent microscopy, are not directly linked to
      any lipofuscin (aging pigment), nor with the anthranilic acid (a product of
      degradation of tryptophan residues of proteins). The main contribution in the
      blue flash of the dying nematodes belongs to parasitic light, scattered on the
      cuticle and bodies of the worm. The main contribution in the blue region at
      spectrofluorometry of homogenates, obtained from nematodes, really gives
      anthranilic acid. However, the content of anthranilic acid, measured by
      spectrofluorimetry, in adult nematodes is lower than that in the young ones.
      Artificial aging of nematodes by moderate heating revealed no accumulation of
      anthranilate and no loss of tryptophan, from which it must be formed. Thus, it is
      hardly lipofuscin or anthranilic acid. The cause of aging and death of nematodes
      is the formation of strong cross-links between proteins. This is supported by
      data on tryptophan fluorescence and light scattering of homogenates: the old
      worms show a large number of denaturated proteins and large protein particles
      with a strong cross-links, which are not destroyed be detergent.

PMID- 29322734
TI  - [The geriatric status in patients with the breast cancer in the conditions of
      comorbidity.]
AB  - The article represents the results of a comparative analysis of the geriatric
      status, the Charlson comorbidity index and the geriatric variant of the
      cumulative illness rating scale for geriatrics (CIRS-G) in patients of different
      age groups with breast cancer, considering the concomitant pathology (CHF). It
      was revealed that the age classification of the WHO is more valid in determining
      the somatic and geriatric status of women with breast cancer. Also the evaluation
      of the severity of geriatric syndromes is given. It was revealed that the
      malnutrition syndrome and cognitive impairment syndrome are more expressed in
      people of middle age and elderly with breast cancer As well the importance of
      detecting both frailty and comorbidity is determined with the aim of increasing
      the accuracy of prediction of adverse events of treatment.

PMID- 29322735
TI  - [Age specific recurrent cancer disability of adult population in the Belgorod
      region in dynamics in 2000-2015.]
AB  - In the Belgorod region for 16 years of observation (2000-2015) number of persons
      who are annually recognized as recurrently disabled due to cancer increased by
      113,4 %. Their specific weight increased from 6,9 up to 24,2 % and its average
      annual rate is 11,3%+/-5,9 of total number of recurrently disabled persons. In
      2015 cancer as a reason of recurrent disability was on the 2d ranking place after
      cardiovascular system diseases. Cohort of persons recognized as recurrently
      disabled due to cancer include mainly persons of average (46,4%+/-9,9) and
      pension (27,7%+/-19,7) age, persons with disability groups II and III (37,2%+/
      4,3 and 50,8%+/-4,1 respectively). With increasing age the degree of the
      recurrently granted disability group gets heavier. Specified negative dynamisc of
      levels, structure and trends of recurrent cancer disability of adult population
      shows the importance and great medical and social as well as economical
      significance of the problem.

PMID- 29322736
TI  - [Effect of combined application of ozone therapy and gravitational therapy on the
      remote results of complex treatment of geriatric patients].
AB  - Skin aging is one of the topical issues in modern gerontocosmetology. Application
      of cosmetic products with short peptides is a promising measure for retardation
      of skin aging. This research is aimed at investigation of KE (Lys-Glu, Vilon)
      dipeptide influence on the expression of markers of aging in human skin
      fibroblasts in vitro. Collagen type I and sirtuin-6 expression in "young" and
      "old" skin cell fibroblasts cultures was studied using immunofluorescence
      confocal microscopy method. The areas of expression of collagen type I and
      sirtuin-6 are known to decrease in skin fibroblasts with aging by 3,5 and 3,6
      times accordingly. KE dipeptide increases collagen type I expression area in
      "old" skin fibroblasts cultures by 83%. KE dipeptide increases expression area of
      sirtuin-6 in "young" and "old" skin fibroblasts cultures by 1,6 and 2,6 times
      correspondingly. Thus, KE dipeptide promotes functional activity of skin
      fibroblasts and inhibits their aging.

PMID- 29322737
TI  - Pulmonary embolism in the hospitalized patients 65+ in relation to presence of
      diabetes in 2007-2015.
AB  - : The aim was to compare an occurrence of acute PE in hospitalized patients 65+
      years old with diabetes mellitus (DM) with those without any DM. It was a
      retrospective analysis of data collected in documentation of patients who were
      hospitalized at the geriatric department in the years 2007-2015. In this period
      we had 11 947 patients of an average age of 79,9+/-8,5 years (min - 65, max - 103
      years). Out of this number there were 4 069 diabetics. Acute PE was found in 344
      patients of an average age 80,3+/-7,4 years. 121 of them died (35,3%) and 223
      survived (64,7%). From total patients 88 were diabetics with PE. Mortality on PE
      did not influence the presence of DM. She was the same in both groups of patients
      (p=NS) - with and without DM. RESULTS: Prevalence PE in the hospitalized 65+
      years old was 2,9%. Mortality of PE among all the hospitalized 65+ was 1,0%.
      Higher prevalence of PE was found in non-diabetics - 3,2%, as compared to the
      diabetics - 2,3% (p<0,025). The average age of patients with diabetes both with
      and without PE was lower as compared to the non-diabetics (p<0,01). Among risk
      factors we found significantly more frequently obesity in the diabetics as
      compared to the non-diabetics both surviving (p<0,001) and those who died
      (p<0,05). The most important risk factor of PE was in all the patient's
      immobility. One risk factor appeared in the set of survivors more frequently in
      the non-diabetics as compared to the diabetics (p<0,05). Simultaneous occurrence
      of three risk factors appeared more frequently in the surviving diabetics
      (p<0,001) as compared to the non-diabetics. Although overall presence of risk
      factors was higher in the diabetics, PE prevalence in the DM patients was lower
      as compared to the non-diabetics. The immobility in general was the most
      important risk factor for PE occurrence, in the diabetics then also obesity.

PMID- 29322738
TI  - [Longterm survival of elderly patients after myocardial infarction depending on
      management in the acute period of the disease.]
AB  - The paper presents the results of study 5-year survival of elderly patient after
      acute myocardial infarction. It is shown that this category of patients, used
      less invasive diagnostic and treatment strategy, compared with younger. In our
      study the effectiveness of primary percutaneous coronary intervention confirmed
      in patients with myocardial infarction with ST-segment elevation (STEMI) in
      relation to long-term survival. However, between the groups of successful
      thrombolytic therapy and pharmacoinvasive treatment strategy, no significant
      differences have been identified. This fact and the conflicting data of modern
      researches in this area confirm that the choice of treatment strategy of acute
      myocardial infarction in the elderly is challenging and requires an individual
      approach.

PMID- 29322739
TI  - [Bone quality of lower limbs in patients with chronic osteomyelitis aged over 60
      years according to multi-slice computed tomography.]
AB  - Radiography and multi-slice computed tomography (MSCT) were used to examine 30
      patients with chronic osteomyelitis of lower limb whose age was over 60 years.
      There were more male patients with posttraumatic osteomyelitis of tibia. 16
      patients were treated for chronic osteomyelitis for more than 5 years and 9
      patients for more than 15 years. Control groups included 30 patients with chronic
      osteomyelitis of long bone aged 20 to 45 years and 30 patients aged 46 to 59
      years. Radiographs of 19 patients of index group (63,3%) showed osteomyelitic
      cavities in the femur and tibia. Radiomorphological changes were observed in the
      adjacent segment of all the patients. Changes in bone architechtonics were
      manifested in expressed polymorphism, without evident signs of osteoporosis due
      to the spread sclerosis in osteomyelitic nidus. Information obtained with MSCT
      preoperatively was comprehensive and revealed location of purulent and necrotic
      nidus, type of destruction, extent and location of involved bone tissue that
      provided a possibility of choice of the most efficient surgical intervention.

PMID- 29322740
TI  - [Hip arthroplasty as a chance to improve quality of life in eldery group of
      patients.]
AB  - Hip arthroplasty outcomes for "difficult" eldery group of patient, aged 75-89
      years, with femoral neck pseudarthrosis were analyzed. All patients were divided
      into 3 groups depending on the type of treatment (surgical or conservative) and
      terms of the removal of previously implanted metal constructions (before or
      during surgical procedure). Good and satisfactory results by Harris hip score
      were achieved in 94,8% of observations. The reasons of postoperative
      complications were considered for every group of patients.

PMID- 29322741
TI  - [Age peculiar by endonasal homeostasis in humans.]
AB  - The state of protective functions of the nasal cavity determines its homeostasis.
      At the stages of postnatal development and involution of functional parameters by
      endonasal homeostasis undergo a number of specific changes, the study of which
      has not only scientific value but also practical value for experimental
      physiology and clinical medicine. The article presents data on the age dynamics
      of functional indicators by endonasal homeostasis of human as buffer properties
      and morphological features of nasal secret. These indicators are examined at the
      stages of postnatal development in a comparative perspective based on the study
      of the age gradients and the position of the doctrine of entropy.

PMID- 29322742
TI  - [The functional state of nasal cavity in the aspect of structural-functional
      changes of the human organism in postnatal ontogenesis.]
AB  - Nasal cavity - "the primary line of defense" and a major division of the
      respiratory tract. A variety of functional areas and regions, structural
      formations of the nasal cavity allows, at the present stage of development of
      biology and medicine, consider it as a complex functional subsystem in the
      structure of the respiratory system. The age transformations of morphological and
      functional parameters of the nasal cavity are polymorphic and specific. An
      important aspect of developmental physiology of the respiratory system is a study
      of the relationship of these changes with morphological and functional
      transformations of other systems of the body. The article presents the results of
      the analysis of such contingency-for example, by endonasal correlations with
      amount of blood flow hemodynamics and functional state of the autonomic nervous
      system, respiratory function of the nasal cavity and respiratory system, as well
      as other functions of the nasal cavity and their relationship with general growth
      processes, critical periods of development and involution. In the process of this
      analysis revealed a close correlation with complex changes of the
      morphofunctional parameters of the systems of the human body, most pronounced
      during in critical periods of postnatal ontogenesis.

PMID- 29322743
TI  - [Studies of the dc-potential of the brain level distribution in elderly women
      with high anxiety.]
AB  - The article presents the results of studies of the direct current (DC) potential
      of the brain level distribution in elderly women with high anxiety. Analysis of
      the DC-potential of the brain level distribution was held by mapping obtained by
      measuring the monopolar values of the DC-potential of the brain and calculating
      deviations in each of the leads from the average records which were registrated
      in all areas of the head. The results of the study indicate an increase in the
      background level of the DC-potential in most parts of the brain and the
      peculiarity of its distribution in elderly women with a high level of anxiety. A
      tendency to deformation of interhemispheric asymmetry with a predominance of
      energy costs in the central region of the right hemisphere and a smoothing of
      interhemispheric asymmetry in the temporal and parietal regions have been
      revealed. The obtained data allow to assume the influence of high anxiety on the
      change in energy metabolism of the brain in the ederly.

PMID- 29322744
TI  - [The compliance of elderly women being at the social institution.]
AB  - The aim of the work is to analyze the prevalence and severity of the
      psychological characteristics of the compliance of elderly women being at the
      social institution in comparison with the same age group living in the family and
      receiving support from relatives. The experimental group of the research
      consisted of 27 women at the age of 70-79 years being at the social institution,
      named Regional State Autonomous Institution Social Welfare "Sedankinsky nursing
      house for the disabled and aged people" of Vladivostok, from 6 to 12 months. As
      well as the comparative group included 27 women at the age of 72-79 years, who
      became widowed and lived in families. The following psychodiagnostic techniques
      were used in the research: Questionnaire "The level of compliance", the technique
      of diagnostics of psychological well-being of the individual, Hospital Anxiety
      and Depression Scale (HADS). The results of this study showed that the low level
      of general, emotional, behavioral and social compliance dominated in the group of
      the elderly women, who lived in the nursing house, in comparison with the group
      of the elderly women living in families. Besides, the level of psychological well
      being is below normal combined with a raised level of depression. In the group
      living in favorable social conditions, viz. in families, the level of general
      compliance is average. Furthermore, the level of psychological well-being is
      characterized as one with better focus on building emotionally close relations
      combined with a sense of meaningfulness of life. The level of depression in the
      comparative group is significantly lower, than in the experimental group. The
      achieved characteristics show the necessity of increasing a compliance level of
      the patients living in the social institutions by carrying out a set of measures
      to optimize the conditions and quality of physician-patient interaction.
      Moreover, it is important not only to teach them to take medicine systematically,
      but also to take an active deliberate position on their own health care.

PMID- 29322745
TI  - [Peculiarities of clinical and psychophysiological status of elderly patients
      with osteochondrosis.]
AB  - We conducted a study of 220 patients in polyclinic No 91 in St. Petersburg. It
      was revealed that elderly patients with osteochondrosis are characterized by a
      high prevalence and severity of osteochondrosis against the background of
      metabolic disorders in the structures of the spine. At the same time, the actual
      condition of the spine does not always determine the severity of the pain
      syndrome. The effect of osteochondrosis on the development of comorbid pathology
      has been clarified. The ways of correction of the clinical and
      psychophysiological status of elderly patients with osteochondrosis such as
      appointment of Cytoflavin, behavioral therapy and biofeed back therapy are
      suggested.

PMID- 29322746
TI  - [Correction of anxiety-depressive disorders in Parkinson's Disease.]
AB  - In the formation of a common age-associated pathological process in patients with
      Parkinson's disease along with movement disorders so-called "non-motorized"
      clinical symptoms (including anxiety and depression) play an important role.
      These pathological manifestations can reduce the quality of life of the patient
      and require specific therapeutic measures. The picker is the use of drugs -
      antidepressants. The article discusses the opportunity for the effective and safe
      use of such drug - sertraline combined with basic therapy, which is widely used
      in Parkinson's disease. Distinct positive results were obtained in the process of
      using the proposed scheme of treatment in 35 patients at the age of 62,3+/-3,6
      years and with disease duration of 3,9+/-2,6 years. We observed decrease
      depressive symptoms, improve sleep, decrease anxiety levels while improving the
      quality of life of patients. No unwanted side effects of the treatment were
      observed. The possibility to use of sertraline for the relief of anxiety and
      depressive disorders in the elderly suffering from Parkinson's disease was shown.

PMID- 29322747
TI  - [Psychophysiological monitoring of women teachers at the turn of the body of
      middle and old age.]
AB  - Objective - to create and hold psychophysiological monitoring elderly organism
      female teachers in the school year dynamics. The study was conducted with the
      participation of 30 female teachers aged 60-61 years at the beginning of the year
      (background level) and 5, and 9 months of teaching in the school. We studied 5
      minute recording portions of the electrocardiogram using a program "Poly-Spectrum
      Rhythm" (the limited liability company "Neurosoft"); lung function - using the
      apparatus "Spirosoft-5000"; psycho-emotional state of teachers in the dynamics of
      the school year - on the method of SUN (state of health, activity, mood). By the
      end of the school year biased increased sympathetic influence of the autonomic
      nervous system on the body of teachers that have been associated with some
      violation of the rhythmic activity of the heart on the background of
      destabilization of sinus rhythm and vegetative balance of the organism;
      indicators of forced expiratory volume in the first second the teachers were not
      significantly below baseline values, indicating a decline in the functional
      reserves of the respiratory system; there has been a strong tendency to
      deterioration of mental and emotional state of women teachers elderly.
      Consequently, the dynamics of the school year it is advisable to monitor the
      activities of the body of female teachers the elderly with a view to the possible
      prevention of various diseases and abnormalities in health status.

PMID- 29322748
TI  - [Features of the new minimally invasive techniques facet fixation system "Facet
      Wedge" in the treatment of degenerative diseases of the lumbar spine in elderly
      patients.]
AB  - The aim of the study was a comparative analysis of the clinical and radiographic
      effectiveness of the use of interbody fusion and open pedicle screw stabilization
      of simultaneous and new minimally invasive techniques facet fixation system
      "Facet Wedge" in the treatment of degenerative diseases of the lumbar spine in
      elderly patients. The study included 39 elderly patients (older than 60), which
      carries out the transforaminal interbody fusion Cage "T-pal": open
      transpedicaular stabilization was used in 1st group (n=23), ipsilateral open
      transpedicular stabilization with contralateral transfaset installing titanium
      Cage "facet Wedge" -in 2nd group (n=16). We used intraoperative interventions and
      specific post-operative patient management, clinical data and radiographic
      outcomes for a comparative analysis of the parameters. Dynamic assessment was
      made in a period of 8 to 36 months after surgery (median 24 mo.). As a result, it
      found that the use of the system "facet Wedge" allows you to achieve the best
      clinical outcomes and fewer postoperative complications compared with open
      transpedicular stabilization in similar radiographic findings of bone block
      formation. Low traumatic facet fixation makes it possible to use methods for the
      treatment of elderly patients with degenerative diseases of the lumbosacral
      spine.

PMID- 29322749
TI  - Time-reversed ultrasonically encoded optical focusing through highly scattering
      ex vivo human cataractous lenses.
AB  - Normal development of the visual system in infants relies on clear images being
      projected onto the retina, which can be disrupted by lens opacity caused by
      congenital cataract. This disruption, if uncorrected in early life, results in
      amblyopia (permanently decreased vision even after removal of the cataract).
      Doctors are able to prevent amblyopia by removing the cataract during the first
      several weeks of life, but this surgery risks a host of complications, which can
      be equally visually disabling. Here, we investigated the feasibility of focusing
      light noninvasively through highly scattering cataractous lenses to stimulate the
      retina, thereby preventing amblyopia. This approach would allow the cataractous
      lens removal surgery to be delayed and hence greatly reduce the risk of
      complications from early surgery. Employing a wavefront shaping technique named
      time-reversed ultrasonically encoded optical focusing in reflection mode, we
      focused 532-nm light through a highly scattering ex vivo adult human cataractous
      lens. This work demonstrates a potential clinical application of wavefront
      shaping techniques.

PMID- 29322750
TI  - Use of Streptococcus salivarius K12 to reduce the incidence of pharyngo
      tonsillitis and acute otitis media in children: a retrospective analysis in not
      recurrent pediatric subjects.
AB  - BACKGROUND: Previous trials, performed in subjects affected by recurrent
      streptococcal pharyngo-tonsillar infection, have shown that the use for 90 days
      of Streptococcus salivarius K12 (K12), an oral colonizing probiotic producing
      lantibiotic bacteriocins, reduces the occurrence of streptococcal and viral
      pharyngitis and acute otitis media (AOM). The aim was to evaluate the role of K12
      in reducing the incidence of streptococcal and viral pharyngo-tonsillitis and AOM
      when administered in two separate trimesters, from October to December and then
      from April to June, in pediatric subjects with non-recurrent streptococcal
      infection. METHODS: We retrospectively analyzed the incidence of pharyngo
      tonsillitis and AOM in 133 children by comparing the number of episodes occurring
      between September 1st, 2014 and August 31st, 2015, when no treatment with K12 was
      given, with the period between September 1st, 2015 and August 31st, 2016, when
      K12 was administered. RESULTS: Analysis of the findings for the 133 children
      demonstrated that K12 use decreased the incidence of pharyngo-tonsillitis by
      about 90% (P<0.001) and the occurrence of AOM by about 70% (P<0.001) and confirms
      the high safety profile of the strain. CONCLUSIONS: As already demonstrated in
      subjects with recurrent streptococcal pharyngo-tonsillar infection, K12, if
      administered for two trimesters out of 12 months, is associated with a reduced
      incidence of pharyngitis and AOM in pediatric subjects with non-recurrent
      streptococcal infection.

PMID- 29322751
TI  - Romosozumab versus Alendronate and Fracture Risk in Women with Osteoporosis.

PMID- 29322752
TI  - Romosozumab versus Alendronate and Fracture Risk in Women with Osteoporosis.

PMID- 29322753
TI  - Romosozumab versus Alendronate and Fracture Risk in Women with Osteoporosis.

PMID- 29322754
TI  - Canakinumab for Atherosclerotic Disease.

PMID- 29322755
TI  - Canakinumab for Atherosclerotic Disease.

PMID- 29322756
TI  - Canakinumab for Atherosclerotic Disease.

PMID- 29322758
TI  - Canakinumab for Atherosclerotic Disease.

PMID- 29322757
TI  - Canakinumab for Atherosclerotic Disease.

PMID- 29322759
TI  - Oxygen Therapy in Suspected Acute Myocardial Infarction.

PMID- 29322760
TI  - Oxygen Therapy in Suspected Acute Myocardial Infarction.

PMID- 29322761
TI  - Electrolyte Disturbances in Chronic Alcohol-Use Disorder.

PMID- 29322762
TI  - Electrolyte Disturbances in Chronic Alcohol-Use Disorder.

PMID- 29322763
TI  - Electrolyte Disturbances in Chronic Alcohol-Use Disorder.

PMID- 29322764
TI  - Rapid Veterinary Diagnosis of Bovine Reproductive Infectious Diseases from Semen
      Using Paper-Origami DNA Microfluidics.
AB  - The health and well-being of cattle is an important issue in maintaining and
      increasing global agricultural output. In dairy production within low and middle
      income countries (LMICs), there is a significant biosensing challenge in
      detecting sexually transmitted infection (STI) pathogens during animal husbandry,
      due in part to difficulties associated with the limited infrastructure for
      veterinary medicine. Here we demonstrate low-cost, multiplexed, and sample-to
      answer paper-origami tests for the detection of three bovine infectious
      reproductive diseases in semen samples, collected at a test site in rural India.
      Pathogen DNA from one viral pathogen, bovine herpes virus-1 (BoHV-1), and two
      bacteria (Brucella and Leptospira) was extracted, amplified (using loop-mediated
      isothermal amplification, LAMP), and detected fluorescently, enabling <1 pg (~
      from 115 to 274 copies per reaction) of target genomic DNA to be measured. Data
      was collected as a fluorescence signal either visually, using a low-cost hand
      held torch, or digitally with a mobile-phone camera. Limits of detection and
      sensitivities of the paper-origami device for the three pathogens were also
      evaluated using pathogen-inoculated semen samples and were as few as 50
      Leptospira organisms, 50 CFU Brucella, and 1 TCID50 BoHV-1. Semen samples from
      elite bulls at a germplasm center were also tested in double-blind tests, as a
      demonstrator for a low-cost, user-friendly point-of-care sensing platform, for in
      the-field resource-limited regions. The sensors showed excellent levels of
      sensitivity and specificity, and for the first time a demonstrated ability of the
      application of paper microfluidics devices for the diagnosis multiple infectious
      diseases from semen samples.

PMID- 29322765
TI  - Influence of Nonstoichiometry on Proton Conductivity in Thin-Film Yttrium-Doped
      Barium Zirconate.
AB  - Proton-conducting perovskites have been widely studied because of their potential
      application as solid electrolytes in intermediate temperature solid oxide fuel
      cells. Structural and chemical heterogeneities can develop during synthesis,
      device fabrication, or service, which can profoundly affect proton transport.
      Here, we use time-resolved Kelvin probe force microscopy, scanning transmission
      electron microscopy, atom probe tomography, and density functional theory
      calculations to intentionally introduce Ba-deficient planar and spherical defects
      and link the resultant atomic structure with proton transport behavior in both
      stoichiometric and nonstoichiometric epitaxial, yttrium-doped barium zirconate
      thin films. The defects were intentionally induced through high-temperature
      annealing treatment, while maintaining the epitaxial single crystalline structure
      of the films, with an overall relaxation in the atomic structure. The annealed
      samples showed smaller magnitudes of local lattice distortions because of the
      formation of proton polarons, thereby leading to decreased proton-trapping
      effect. This resulted in a decrease in the activation energy for proton
      transport, leading to faster proton transport.

PMID- 29322766
TI  - Largely Tunable Band Structures of Few-Layer InSe by Uniaxial Strain.
AB  - Because of the strong quantum confinement effect, few-layer gamma-InSe exhibits a
      layer-dependent band gap, spanning the visible and near infrared regions, and
      thus recently has been drawing tremendous attention. As a two-dimensional
      material, the mechanical flexibility provides an additional tuning knob for the
      electronic structures. Here, for the first time, we engineer the band structures
      of few-layer and bulk-like InSe by uniaxial tensile strain and observe a salient
      shift of photoluminescence peaks. The shift rate of the optical gap is
      approximately 90-100 meV per 1% strain for four- to eight-layer samples, which is
      much larger than that for the widely studied MoS2 monolayer. Density functional
      theory calculations well reproduce the observed layer-dependent band gaps and the
      strain effect and reveal that the shift rate decreases with the increasing layer
      number for few-layer InSe. Our study demonstrates that InSe is a very versatile
      two-dimensional electronic and optoelectronic material, which is suitable for
      tunable light emitters, photodetectors, and other optoelectronic devices.

PMID- 29322767
TI  - pH-Dependent Switching of Base Pairs Using Artificial Nucleobases with Carboxyl
      Groups.
AB  - In this study, we report the synthesis of modified oligonucleotides consisting of
      benzoic acid or isophthalic acid residues as new nucleobases. As evaluated by UV
      thermal denaturation analysis at different pH conditions (5.0, 6.0, 7.0, and
      8.0), these modified oligonucleotides exhibited pH-dependent recognition of
      natural nucleobases and one is first found to be capable of base pair switching
      in response to a pH change. The isophthalic acid residue incorporated into the
      oligonucleotide on a d-threoninol backbone could preferentially bind with adenine
      but with guanine in response to a change in the pH conditions from pH 5 to pH 7
      (or 8) without significant difference in duplex stability. These findings would
      be valuable for further developing pH-responsive DNA-based molecular devices.

PMID- 29322768
TI  - Identification of Novel "Inks" for 3D Printing Using High-Throughput Screening:
      Bioresorbable Photocurable Polymers for Controlled Drug Delivery.
AB  - A robust methodology is presented to identify novel biomaterials suitable for
      three-dimensional (3D) printing. Currently, the application of additive
      manufacturing is limited by the availability of functional inks, especially in
      the area of biomaterials; this is the first time when this method is used to
      tackle this problem, allowing hundreds of formulations to be readily assessed.
      Several functional properties, including the release of an antidepressive drug
      (paroxetine), cytotoxicity, and printability, are screened for 253 new ink
      formulations in a high-throughput format as well as mechanical properties. The
      selected candidates with the desirable properties are successfully scaled up
      using 3D printing into a range of object architectures. A full drug release study
      and degradability and tensile modulus experiments are presented on a simple
      architecture to validating the suitability of this methodology to identify
      printable inks for 3D printing devices with bespoke properties.

PMID- 29322769
TI  - Composition, Microstructure, and Electrical Performance of Sputtered SnO Thin
      Films for p-Type Oxide Semiconductor.
AB  - p-Type SnO thin films were deposited on a Si substrate by a cosputtering process
      using ceramic SnO and metal Sn targets at room temperature without adding oxygen.
      By varying the dc sputtering power applied to the Sn target while maintaining a
      constant radio frequency power to the SnO target, the Sn/O ratio varied from
      56:44 to 74:26 at the as-deposited state. After thermal annealing at 180  degrees
      C for 25 min under air atmosphere using a microwave annealing system, the films
      were crystallized into tetragonal SnO when the Sn/O ratio increased from 44:56 to
      57:43. Notably, the metallic Sn remained when the Sn/O ratio was higher than
      55:45 at an annealed state. When the ratio was lower than 55:45 at the annealed
      state, the incorporated Sn fully oxidized to SnO, making the films useful p-type
      semiconductors, whereas the films became metallic conductors at higher Sn/O
      ratios. At the Sn/O ratio of 55:45 at the annealed state, the film showed the
      highest Hall mobility of 8.8 cm2 V-1 s-1 and a hole concentration of 5.4 * 1018
      cm-3. Interestingly, the electrical conduction behavior showed trap-mediated
      hopping when the Sn metal was cosputtered, whereas the single SnO film showed
      regular band conduction behavior. The residual stress effect could interpret such
      property variation originated from the sputtering power and postoxidation-induced
      volumetric effects. This report makes a critical contribution to the in-depth
      understanding of the composition-structure-property relationship of this
      technically important thin film material.

PMID- 29322770
TI  - High-Performance Quantum Dot Thin-Film Transistors with Environmentally Benign
      Surface Functionalization and Robust Defect Passivation.
AB  - The recent development of high-performance colloidal quantum dot (QD) thin-film
      transistors (TFTs) has been achieved with removal of surface ligand, defect
      passivation, and facile electronic doping. Here, we report on high-performance
      solution-processed CdSe QD-TFTs with an optimized surface functionalization and
      robust defect passivation via hydrazine-free metal chalcogenide (MCC) ligands.
      The underlying mechanism of the ligand effects on CdSe QDs has been studied with
      hydrazine-free ex situ reaction derived MCC ligands, such as Sn2S64-, Sn2Se64-,
      and In2Se42-, to allow benign solution-process available. Furthermore, the defect
      passivation and remote n-type doping effects have been investigated by
      incorporating indium nanoparticles over the QD layer. Strong electronic coupling
      and solid defect passivation of QDs could be achieved by introducing
      electronically active MCC capping and thermal diffusion of the indium
      nanoparticles, respectively. It is also noteworthy that the diffused indium
      nanoparticles facilitate charge injection not only inter-QDs but also between
      source/drain electrodes and the QD semiconductors, significantly reducing contact
      resistance. With benign organic solvents, the Sn2S64-, Sn2Se64-, and In2Se42-
      ligand based QD-TFTs exhibited field-effect mobilities exceeding 4.8, 12.0, and
      44.2 cm2/(V s), respectively. The results reported here imply that the
      incorporation of MCC ligands and appropriate dopants provide a general route to
      high-performance, extremely stable solution-processed QD-based electronic devices
      with marginal toxicity, offering compatibility with standard complementary metal
      oxide semiconductor processing and large-scale on-chip device applications.

PMID- 29322771
TI  - Tunable Valley and Spin Polarizations in BiXO3/BiIrO3 (X = Fe, Mn) Ferroelectric
      Superlattices.
AB  - The generation and modulation on valley and spin degrees of freedom are essential
      for multifunctional electronic devices. Herewith, the electronic structures in
      BiXO3/BiIrO3 (X = Fe, Mn) ferroelectric superlattices are studied by first
      principles calculations with spin-orbital coupling. Different from the previous
      BiAlO3/BiIrO3 system, both valley and spin polarizations in bilayered BiIrO3 are
      achieved in BiXO3/BiIrO3 superlattices, where the spin polarization in the valley
      can be engineered by the spin orientation of Fe or Mn owing to the xy-plane
      orbitals. Especially, the relatively parallel and antiparallel directions of
      ferroelectric polarization in BiFeO3 and BiIrO3 can switch the valley injection
      in BiFeO3/BiIrO3 superlattices. Overall, the tunable valley and spin
      polarizations in BiFeO3/BiIrO3 ferroelectric superlattices pave a way for
      developing nonvolatile data memories and valley-spin devices.

PMID- 29322772
TI  - Stable Aluminum Metal-Organic Frameworks (Al-MOFs) for Balanced CO2 and Water
      Selectivity.
AB  - Three new Al-MOFs in the formation of [Al4(OH)2(OCH3)4(OH-BDC)3].xH2O (BIT-72),
      [Al4(OH)2(OCH3)4(CH3-BDC)3].xH2O (BIT-73) and {Al4(OH)2(OCH3)4[(CH3)2-BDC]3}.xH2O
      (BIT-74) have been synthesized by assembling Al3+ ion with terephthalic acid ions
      decorated with monohydroxyl, monomethyl or dimethyl groups, respectively. All of
      these three MOFs exhibit high stability in boiling water and acidic conditions.
      Among them, BIT-72 shows the highest surface area of 1618 m2.g-1 and IAST CO2/N2
      selectivity of 48, while BIT-73 and BIT-74 present moderate IAST CO2/N2
      selectivity and much lower H2O capacity below P/P0 = 0.3. The high CO2/N2
      selectivity together with alleviative H2O sorption at low water relative pressure
      may provide promising potential in postcombustion CO2 capture.

PMID- 29322773
TI  - Surface-Enhanced Raman Spectroscopy-Based Label-Free Insulin Detection at
      Physiological Concentrations for Analysis of Islet Performance.
AB  - Label-free optical detection of insulin would allow in vitro assessment of
      pancreatic cell functions in their natural state and expedite diabetes-related
      clinical research and treatment; however, no existing method has met these
      criteria at physiological concentrations. Using spatially uniform 3D gold
      nanoparticle sensors, we have demonstrated surface-enhanced Raman sensing of
      insulin in the secretions from human pancreatic islets under low and high glucose
      environments without the use of labels such as antibodies or aptamers. Label-free
      measurements of the islet secretions showed excellent correlation among the
      ambient glucose levels, secreted insulin concentrations, and measured Raman
      emission intensities. When excited at 785 nm, plasmonic hotspots of the densely
      arranged 3D gold-nanoparticle pillars as well as strong interaction between
      sulfide linkages of the insulin molecules and the gold nanoparticles produced
      highly sensitive and reliable insulin measurements down to 100 pM. The sensors
      exhibited a dynamic range of 100 pM to 50 nM with an estimated detection limit of
      35 pM, which covers the reported concentration range of insulin observed in
      pancreatic cell secretions. The sensitivity of this approach is approximately 4
      orders of magnitude greater than previously reported results using label-free
      optical approaches, and it is much more cost-effective than immunoassay-based
      insulin detection widely used in clinics and laboratories. These promising
      results may open up new opportunities for insulin sensing in research and
      clinical applications.

PMID- 29322774
TI  - Visible-Light-Induced Decarboxylation Coupling/Intramolecular Cyclization: A One
      Pot Synthesis for 4-Aryl-2-quinolinone Derivatives.
AB  - A visible-light-induced decarboxylation coupling/intramolecular cyclization is
      reported. The one-pot synthesis system provides mild, efficient, and atom
      economical access to the synthesis of 4-aryl-2-quinolinone derivatives. It is
      notable that the necessary oxidant in the traditional decarboxylation coupling is
      replaced by the visible-light irradiation in this paper. In addition, the HBV
      inhibitor is synthesized by the one-pot synthesis system in an atom economical
      manner.

PMID- 29322775
TI  - Effect of Metal Doping and Vacancies on the Thermal Conductivity of Monolayer
      Molybdenum Diselenide.
AB  - It is well understood that defect engineering can give rise to exotic electronic
      properties in transition-metal dichalcogenides, but to this date, there is no
      detailed study to illustrate how defects can be engineered to tailor their
      thermal properties. Here, through combined experimental and theoretical
      approaches based on the first-principles density functional theory and Boltzmann
      transport equations, we have explored the effect of lattice vacancies and
      substitutional tungsten (W) doping on the thermal transport of the suspended
      molybdenum diselenide (MoSe2) monolayers grown by chemical vapor deposition
      (CVD). The results show that even though the isoelectronic substitution of the W
      atoms for Mo atoms in CVD-grown Mo0.82W018Se2 monolayers reduces the Se vacancy
      concentration by 50% compared to that found in the MoSe2 monolayers, the thermal
      conductivity remains intact in a wide temperature range. On the other hand, Se
      vacancies have a detrimental effect for both samples and more so in the
      Mo0.82W018Se2 monolayers, which results in thermal conductivity reduction up to
      72% for a vacancy concentration of 4%. This is because the mass of the W atom is
      larger than that of the Mo atom, and missing a Se atom at a vacancy site results
      in a larger mass difference and therefore kinetic energy and potential energy
      difference. Furthermore, the monotonically increasing thermal conductivity with
      temperature for both systems at low temperatures indicates the importance of
      boundary scattering over defects and phonon-phonon scattering at these
      temperatures.

PMID- 29322776
TI  - Altered Serum Metabolite Profiling and Relevant Pathway Analysis in Rats
      Stimulated by Honeybee Venom: New Insight into Allergy to Honeybee Venom.
AB  - To improve our understanding of the disturbed metabolic pathways and cellular
      responses triggered by honeybee venom stimulation, we compared the changes in
      serum metabolites in rats, either stimulated or not by honeybee venom, by
      performing 1H nuclear magnetic resonance (NMR) spectrometry-based metabonomics to
      identify potential biomarkers. In this study, 65 metabolites were structurally
      confirmed and quantified and the following results were obtained. First, by
      pattern recognition analysis, 14 metabolites were selected as potential
      biomarkers 3 h after venom stimulation. Second, metabolic pathway analysis showed
      that methane metabolism, glyoxylate and dicarboxylate metabolism, tricarboxylic
      acid cycle, glycine, serine, and threonine metabolism, arginine and proline
      metabolism were affected. Finally, the time-dependent metabolic modifications
      indicated that rats could recover without medical treatment 24 h after venom
      stimulation. In summary, this new insight into the changes in serum metabolites
      in rats after honeybee venom stimulation has enhanced our understanding of the
      response of an organism to honeybee venom.

PMID- 29322777
TI  - Skeletal Reorganization: Synthesis of Diptoindonesin G from Pauciflorol F.
AB  - Described herein is a novel synthetic approach to diptoindonesin G, a highly
      potent anticancer oligostilbenoid natural product, from pauciflorol F pentamethyl
      ether through a skeletal reorganization strategy where oxidative cleavage of the
      indanone ring system of pauciflorol F and sequential cyclization of the key
      intermediate allowed direct access to the target skeleton.

PMID- 29322780
TI  - Signal and Noise in FET-Nanopore Devices.
AB  - The combination of a nanopore with a local field-effect transistor (FET
      nanopore), like a nanoribbon, nanotube, or nanowire, in order to sense single
      molecules translocating through the pore is promising for DNA sequencing at
      megahertz bandwidths. Previously, it was experimentally determined that the
      detection mechanism was due to local potential fluctuations that arise when an
      analyte enters a nanopore and constricts ion flow through it, rather than the
      theoretically proposed mechanism of direct charge coupling between the DNA and
      nanowire. However, there has been little discussion on the experimentally
      observed detection mechanism and its relation to the operation of real devices.
      We model the intrinsic signal and noise in such an FET-nanopore device and
      compare the results to the ionic current signal. The physical dimensions of DNA
      molecules limit the change in gate voltage on the FET to below 40 mV. We discuss
      the low-frequency flicker noise (<10 kHz), medium-frequency thermal noise (<100
      kHz), and high-frequency capacitive noise (>100 kHz) in FET-nanopore devices. At
      bandwidths dominated by thermal noise, the signal-to-noise ratio in FET-nanopore
      devices is lower than in the ionic current signal. At high frequencies, where
      noise due to parasitic capacitances in the amplifier and chip is the dominant
      source of noise in ionic current measurements, high-transconductance FET-nanopore
      devices can outperform ionic current measurements.

PMID- 29322779
TI  - Mining the Secretome of C2C12 Muscle Cells: Data Dependent Experimental Approach
      To Analyze Protein Secretion Using Label-Free Quantification and Peptide Based
      Analysis.
AB  - Secretome analysis faces several challenges including detection of low abundant
      proteins and the discrimination of bona fide secreted proteins from false
      positive identifications stemming from cell leakage or serum. Here, we developed
      a two-step secretomics approach and applied it to the analysis of secreted
      proteins of C2C12 skeletal muscle cells since the skeletal muscle has been
      identified as an important endocrine organ secreting myokines as signaling
      molecules. First, we compared culture supernatants with corresponding cell
      lysates by mass spectrometry-based proteomics and label-free quantification. We
      identified 672 protein groups as candidate secreted proteins due to their higher
      abundance in the secretome. On the basis of Brefeldin A mediated blocking of
      classical secretory processes, we estimated a sensitivity of >80% for the
      detection of classical secreted proteins for our experimental approach. In the
      second step, the peptide level information was integrated with UniProt based
      protein information employing the newly developed bioinformatics tool "Lysate and
      Secretome Peptide Feature Plotter" (LSPFP) to detect proteolytic protein
      processing events that might occur during secretion. Concerning the proof of
      concept, we identified truncations of the cytoplasmic part of the protein Plexin
      B2. Our workflow provides an efficient combination of experimental workflow and
      data analysis to identify putative secreted and proteolytic processed proteins.

PMID- 29322781
TI  - Ab Initio Study Predicts That Enigmatic Isonitrosyl Fluoride Should Be Stable at
      Low Temperatures yet Unnoticeable Due to Its Photoreactivity.
AB  - Isonitrosyl fluoride F-ON remains an undetected molecule despite multiple
      attempts to generate it and successful identification of other isonitrosyl
      halides (X-ONs) via phototransformations of corresponding X-NOs. We investigated
      this problem using ab initio methods and found no evidence of instability of F-ON
      at low temperatures of 8-10 K. Instead, experimental observation of F-ON is
      likely challenged by the (1) different nature of photoexcitation of F-NO and its
      quantum yield being lower than those of other X-NOs and (2) the presence of a
      bright charge-transfer transition in the F-ON spectrum that likely overlaps with
      the weak band of F-NO used for photoexcitation. Formation of F-ON via symmetry
      prohibited photoexcitation of F-NO is followed by its immediate
      photodecomposition to the charge-transfer excited state and its conversion to F
      NO upon de-excitation. Thus, F-ON should be readily observable using non
      photochemistry methods such as microwave spectroscopy.

PMID- 29322782
TI  - Aerobic Oxidation of Alkyl 2-Phenylhydrazinecarboxylates Catalyzed by CuCl and
      DMAP.
AB  - Recently, various fruitful organic reactions such as a catalytic Mitsunobu
      reaction were reported by virtue of alkyl 2-phenylazocarboxylates, however, the
      synthesis of alkyl 2-phenylazocarboxylates largely depended on the stoichiometric
      use of toxic oxidants. In this manuscript, an environment-friendly aerobic
      oxidative transformation of alkyl 2-phenylhydrazinecarboxylates to alkyl 2
      phenylazocarboxylates is disclosed. The use of CuCl and DMAP system efficiently
      catalyzed the aerobic oxidation of alkyl 2-phenylhydrazinecarboxylates under mild
      conditions. The reaction rate of the present Cu-catalysis was much faster than
      that of the previously reported Fe-catalysis, and a variety of azo products were
      synthesized within 3 h. The present protocol was effective on larger scale. It
      was observed that the produced azo compound could undergo various reactions
      without isolation through one-pot sequential protocols.

PMID- 29322783
TI  - MicroRNAs in triple-negative breast cancer.
AB  - Triple-negative breast cancer (TNBC) is a molecular subtype of breast cancer with
      one of the worst prognoses. Current treatment is based on chemo- and/or
      radiotherapy and surgery. New targets, however, offering other therapeutic
      approaches, have been identified. These involve poly (ADP-ribose) polymerase
      (PARP), vascular endothelial growth factor receptor (VEGFR), epidermal growth
      factor receptor (EGFR), androgen receptor (AR), long non-coding RNAs (lncRNAs)
      and microRNAs (miRs). The latter are non-coding RNAs which control the expression
      of more than 50% of human genes via regulation of basic cellular processes at
      post-transcriptional level and dysregulation of miRs is found in many types of
      tumors. The role of dysregulated miRs in carcinogenesis lies in their acting as
      tumor suppressors or oncogenes, and in resistance to treatment (chemotherapy,
      hormonal and targeted therapy or radiotherapy). Circulating miRs are also
      promising prognostic and predictive biomarkers in patients with breast cancer.
      The aim of this review is to analyze recently published data on miRs and
      therapeutic targets potentially influenced by miRs in TNBC.

PMID- 29322784
TI  - Bioinformatic analysis of changes in RNA polymerase II transcription stimulated
      by estradiol in MCF7 cells.
AB  - Estradiol (E2) is the most potent estrogen and RNA polymerase II (Pol II)
      regulates a great mass of gene expression. This study was designed to illustrate
      the mechanisms of estrogen-dependent human breast cancer (BC) through Pol II.
      ChIP-seq data, DNase-seq data and other sequencing data of human BC MCF-7 cells
      were downloaded from Gene Expression Omnibus database. Each of these datasets
      included one control and one E2 treated sample. Sequence alignment was performed
      and Pol II factor binding signal was determined. Functional enrichment analysis
      of particular genes was performed, along with transcription factor (TF) motif
      enrichment analysis. Sites with enhanced Pol II binding were identified in
      intergenic regions. Pol II binding sites with increased binding signal
      facilitated chromosome switching from a closed to an open state. A total of 59
      TFs, including KLF4 (Kruppel-like factor 4), were identified. Besides, enrichment
      analysis revealed that protein synthesis and metabolic processes as well as cell
      cycle processes were highlighted. The KLF4 motif was found to be enriched and was
      significantly enhanced in the promoter region for Pol II binding. Cell cycle
      processes, protein synthesis and metabolism play critical roles in the
      progression of E2-stimulated BC. In addition, KLF4 may be important for the
      progression.

PMID- 29322785
TI  - Triptolide induces mitochondrial apoptosis through modulating dual specificity
      phosphatase 1/mitogen-activated protein kinases cascade in osteosarcoma cells.
AB  - Due to chemoresistance and metastasis, the overall prognosis of osteosarcoma (OS)
      has not improved over the last two decades. Exploring novel therapeutic agents
      that can circumvent theses malignant phenotypes of OS would be essential to
      improve the survival of OS patients. Triptolide is a unique diterpene triepoxide
      that possesses potent antitumor activities.However, the effects and mechanism of
      triptolide on OS cells remain unknown. The effects of triptolide on viability,
      apoptosis, cell cycle distribution and migratory ability of OS cells were
      measured using MTT, flow cytometry and wound healing and transwell invasion
      assays. And an OS tumor xenograft mouse model was produced to further study the
      in vivo antitumor effects of triptolide. The expression of DUSP1 at the protein
      and mRNA level in OS cells was detected by western blot and qPCR. We report that
      triptolide exhibits multidimensional antitumor activities in OS cells, including
      the induction of apoptosis and G1 phase accumulation, inhibition of cell
      viability, migration, and invasion. We further demonstrate that triptolide
      inhibits the expression of dual-specificity protein phosphatase1 (DUSP1) through
      inhibiting its promoter activity, which causes sustained activation of three
      subfamilies of mitogen-activated protein kinase (MAPK). And the modulation of
      DUSP1/MAPK cascade is associated with the apoptosis of OS cells, since the
      ectopic expression of DUSP1 or the inhibition of MAPK using specific inhibitors
      can counteract triptolide-induced apoptosis. In addition, triptolide enhances
      doxorubicin-induced apoptosis. In summary, our study suggests that DUSP1 is an
      important cellular target of triptolide, and triptolide may be a promising
      treatment option for OS as a single agent or combined with other
      chemotherapeutics.

PMID- 29322786
TI  - CCAAT enhancer binding protein beta promotes tumor growth and inhibits apoptosis
      in prostate cancer by methylating estrogen receptor beta.
AB  - The CCAAT enhancer binding protein beta (C/EBPbeta) is overexpressed at late
      stages in carcinogenesis of prostate cancer (PCa), suggesting that it could
      potentially contribute to progression of PCa. Estrogen receptor beta (ERbeta) is
      a tumor suppressor gene in PCa. However, whether C/EBPbeta could regulate ERbeta
      by promoter methylation is still poorly understood.In this study, expression
      levels of C/EBPbeta and ERbeta in two PC lines (LNCap and PC-3), prostatic
      epithelial cell line (RWPE-1), forty-eight paired non-cancerous and cancerous
      peripheral blood samples were examined via qRT-PCR, western blotting and
      methylation-specific PCR. In addition, PCa cell line was infected with pCDH
      C/EBPbeta and pLKO.1-C/EBPbeta and expression levels of C/EBPbeta, ERbeta and DNA
      methyltransferases were detected. Finally, the role of C/EBPbeta in proliferation
      and apoptosis of PCa cell lines was examined by MTT and flow cytometer assay. Our
      results show a higher frequency of promoter methylation of ERbeta levels in blood
      samples from PCa patients (16 of 48 cases) compared with that from healthy
      controls (3 of 48). Besides, elevated expression levels of C/EBPbeta were found
      in PCa patients and two PCa lines (LNCap and PC-3) compared to non-cancerous
      cases or prostatic epithelial cell line (RWPE-1), while opposite expression
      levels of ERbeta were found. Overexpression of C/EBPbeta could regulate ERbeta
      expression, DNA methyltransferases expression, cell proliferation and apoptosis.
      Our results support the conclusion that C/EBPbeta down-regulated ERbeta
      expression through increasing its promoter methylation, and then regulated
      proliferation and apoptosis in PCa.

PMID- 29322787
TI  - Beclin1 enhances cisplatin-induced apoptosis via Bcl-2-modulated autophagy in
      laryngeal carcinoma cells Hep-2.
AB  - To investigate the role of Beclin1 in cisplatin-induced apoptosis in laryngeal
      carcinoma cells Hep-2 and to explore the potential mechanism. We up-regulated
      Beclin1 expression in Hep-2 cells. The survival rate and apoptotic rate were
      evaluated by MTT and flow cytometry (FCM). The Beclin1 overexpression group and
      the control group were treated with cisplatin for 24 hours. The proliferation and
      cell apoptosis of laryngeal cancer cell lines were evaluated. The mitochondrial
      membrane potentials were detected by DiOC6(3). Activities of Caspase-8/9/3 and
      convention of microtubule-associated protein one light chain 3 (LC3) were
      detected by western blot. The effect of Bcl-2 overexpression on increased
      cisplatin-sensitivity and autophagy induced by Beclin1 was investigated using Bcl
      2 cDNA transfection. Expression of Beclin1 in Hep-2 cells was meaningfully
      enhanced by transfection, and the proliferation and the apoptosis were not
      considerably affected. By cisplatin treatment, the Beclin1 overexpression group
      showed lower survival rate and higher apoptotic rate than the control group
      (p<0.05). Decrease of mitochondrial membrane potential and increase of activities
      of Caspase-8, Caspase-9 and Caspase-3 were detected. Beclin1 overexpression
      increase the convention of LC3, especially after the cisplatin treatment.
      Overexpression of Bcl-2 decreased the cisplatin-induced apoptosis and inhibited
      Beclin1-induced autophagy. In conclusion, Beclin1 enhances cisplatin-induced
      apoptosis in laryngeal carcinoma cells Hep-2 via Bcl-2 modulated autophagy.

PMID- 29322788
TI  - MicroRNA-421 inhibits caspase-10 expression and promotes breast cancer
      progression.
AB  - Breast cancer is one of the most prevalent and fatal diseases around the world.
      The mechanism of tumorigenesis in breast cancer remains to be clarified. miR-421
      plays an oncogenic role in many cancers. Although, the clinical significance of
      miR-421 in patients with breast cancer is still to be investigated. Caspase-10 is
      one of the initiator of apoptosis. But the relationship between miR-421 and
      caspase-10 has not been investigated. In the present study, we found that miR-421
      was expressed much higher in breast cancer tissues compared to those in adjacent
      non-tumor tissues. Furthermore, miR-421 promotes cell proliferation and colony
      formation in vitro. miR-421 inhibits cell apoptosis probably through restraining
      caspase-10 expression. Thus, miR-421 might be a potential diagnostic maker and
      therapeutic target for breast cancer.

PMID- 29322789
TI  - RNA interference-mediated silencing of aquaporin (AQP)-5 hinders angiogenesis of
      colorectal tumor by suppressing the production of vascular endothelial growth
      factor.
AB  - Aquaporin (AQP)-5 is an essential member of AQP family involved in the
      tumorigenesis of various malignant tumors. However, its role in the angiogenesis
      of colorectal cancer is unclear and requires further investigation. In this
      study, a pRNA-H1.1 vector containing the short hairpin RNA (shRNA) targeting AQP5
      mRNA was constructed to inhibit the endogenous expression of AQP5 in human
      umbilical vein endothelial cells (HUVECs). We found that the AQP5-silenced HUVECs
      acquired decreased proliferation, migration and tube formation ability. AQP5
      shRNA also inhibited the enzyme activity of matrix metalloprotease (MMP)-9 in
      HUVECs without affecting the MMP-2. Further, two colorectal cancer cell lines
      (HT29 and HCT116) stably transfected with scrambled or AQP5 shRNA were
      established. The expression and secretion of vascular endothelial growth factor
      (VEGF)-A (a pro-angiogenic factor) in colorectal cancer cells were downregulated
      by AQP5 shRNA. HUVECs cultured in low-VEGF conditioned media (CM) obtained from
      cancer cells developed less vessel-like tubes and had decreased proliferation and
      migration. The growth and angiogenesis of xenograft tumors were suppressed when
      the endogenous AQP5 in HT29 cells was knocked down. Tumor samples were
      additionally collected from patients with colorectal cancer to analyze the
      expression of AQP5. The immunofluorescence data indicated that AQP5 was expressed
      in both inner cancer areas and CD31-positive vessels. Taken together, our study
      suggests AQP5 as a novel anti-angiogenesis target for colorectal cancer.

PMID- 29322790
TI  - Integrated network analysis to identify the key genes, transcription factors, and
      microRNAs involved in hepatocellular carcinoma.
AB  - HCC (hepatocellular carcinoma), which can be induced by cirrhosis and viral
      hepatitis infection, is the most frequent form of liver cancer. This study is
      performed to investigate the mechanisms of HCC. GSE57957 was obtained from Gene
      Expression Omnibus database, including 39 HCC samples and 39 adjacent non
      tumorous samples. The DEGs (differentially expressed genes) were screened using
      the limma package in R, and then were conducted with enrichment analysis using
      "BioCloud" platform. Using STRING database, WebGestalt tool, as well as ITFP and
      TRANSFAC databases, PPI (protein-protein interaction) pairs, miRNA (microRNA)
      target pairs, and TF (transcription factor)-target pairs separately were
      predicted. Followed by integrated network was constructed by Cytoscape software
      and module analysis was performed using the MCODE plugin of Cytoscape software.
      There were 518 DEGs identified from the HCC samples, among which 17 up-regulated
      genes (including MCM2, MCM6, and CDC20) and 5 down-regulated genes could also
      function as TFs. In the integrated network for the down-regulated genes, FOS and
      ESR1 had higher degrees, and both of them were targeted by miR-221 and miR-222.
      Additionally, MCM2 had interaction with MCM6 in the up-regulated module with the
      highest score. MCM2, MCM6, CDC20, FOS, ESR1, miR-221 and miR-222 might affect the
      pathogenesis of HCC.

PMID- 29322791
TI  - Targeting RAD50 increases sensitivity to radiotherapy in colorectal cancer cells.
AB  - Radiotherapy resistance remains the major factor limiting the radiotherapy
      efficacy in colorectal cancer. The Mre11-RAD50-Nbs1 (MRN) complex is known to
      play a critical role in the DNA double strand breaks (DSBs) repair pathways and
      thus facilitates radioresistance. Targeting MRN function can sensitize cancer
      cells to irradiation in some malignancies. In this study, we stably knocked down
      RAD50 protein in colorectal cancer (CRC) cell lines, HCT116 and DLD1, and
      evaluated their response to irradiation as well as the DSB repair dynamics. We
      observed that downregulation of RAD50 sensitized CRC cells to irradiation with
      reduction in DSB repair efficiency after exposure to irradiation. In addition,
      RAD50 was found to be upregulated in CRC cancerous tissue samples compared to non
      cancerous adjacent tissues (NATs) and in patients who were resistant to RT.
      Elevated RAD50 expression was associated with poor patient survival in CRC. In
      conclusion, targeting RAD50 can serve as an efficient strategy to sensitize CRC
      cells to irradiation. RAD50 protein may be used as a biomarker for patient
      survival in CRC.

PMID- 29322792
TI  - KrasG12D-LOH promotes malignant biological behavior and energy metabolism of
      pancreatic ductal adenocarcinoma cells through the mTOR signaling pathway.
AB  - Oncogenic Kras with loss of heterozygosity (LOH) is frequently detected in
      various tumours. However, the exact function and mechanism by which KrasG12D-LOH
      operates remain unclear. Therefore, the current study investigated the effect of
      KrasG12D-LOH on the malignant phenotype of pancreatic ductal adenocarcinoma
      (PDAC) cells. Our investigation revealed that KrasG12D-LOH is associated with
      increased proliferation, invasion and reduced apoptosis in PDAC cells. The
      results also exhibited enhanced glycolytic phenotype of KrasG12D-LOH PDAC cells.
      Hyperactive mTOR plays a significant role in the initiation and maintenance of
      tumors. To investigate the correlation between KrasG12D-LOH and mTOR, the mTOR
      signaling pathway was detected by western blot analysis. We found that KrasG12D
      LOH up-regulated Akt, AMPK, REDD1 and mTOR in PDAC cells. In summary, our results
      demonstrated that KrasG12D-LOH promotes oncogenic Kras-induced PDAC by regulating
      energy metabolism and mTOR signaling pathway. These data may provide novel
      therapeutic perspectives for PDAC.

PMID- 29322793
TI  - MiR-1-3p inhibits cell proliferation and invasion by regulating BDNF-TrkB
      signaling pathway in bladder cancer.
AB  - Recent studies have confirmed the existence of BDNF and tropomyosin-related
      kinase B (TrkB) in normal and cancerous urothelium. However, the corresponding
      mechanisms and upstream signal pathways of BDNF/TrkB have not been fully
      discovered. This study aimed to investigate the effects of miR-1-3p on bladder
      cancer (BC) by regulating BDNF-TrkB signal pathway. The expression of miR-1-3p
      and BDNF in BC tissues and cell lines were detected by Cancer Genome Atlas (TCGA)
      microarray analysis, RT-qPCR and western blot. Cell transfection was done using
      Lipofectamine 2000. Then cell viability, proliferation, migration and apoptosis
      were measured by MTT, colony formation assay, Transwell assay and flow cytometry,
      respectively. The relationship between miR-1-3p and BDNF was confirmed by
      luciferase reporter gene assay. MiR-1-3p was significantly down-regulated in BC
      tissues and cell lines, while BDNF was significantly up-regulated compared to
      normal samples. MiR-1-3p targeted BDNF and suppressed its expression.
      Transfections of miR-1-3p mimics and BDNF siRNAs can suppress BC cell
      proliferation, invasion and induce cell apoptosis. In addition, miR-1-3p can
      inhibit phosphorylation of the TrkB by regulating BDNF.In conclusion, MiR-1-3p
      has significant effects on viability, proliferation, invasion and apoptosis of BC
      cells by regulating BDNF-TrkB pathway.

PMID- 29322794
TI  - Integrated analysis of the RNA-Seq data of liver hepatocellular carcinoma.
AB  - The present study aimed to explore the genetic changes involved in the liver
      hepatocellular carcinoma (HCC) development. The RNA-Seq data of 212 HCC tissue
      samples and 50 normal tissue samples were downloaded using TCGA-Assembler. A
      total of 4 subgroups were obtained, and 4167, 6279, 5379, and 2548 DEGs were
      screened in group 1, group 2, group 3, and group 4, respectively. Enrichment
      analysis found that cell cycle, metabolism, and translation related terms were
      the most significantly changed functions and pathways. There were 454 genes (1114
      pairs), 803 genes (722 pairs), and 788 genes (724 pairs), separately interacted
      in the condition specific PPI network of group 1, 2, 3, and 4, with MMP2, ATNXN1,
      F2, and HDAC1 as the hub genes. What's more, using these genes, total 7, 20, 198,
      and 1 subtype related miRNAs; 35, 50, 47, and 17 subtype related TFs; 1, 1, 0,
      and 2 subtype related drugs were screened in group 1, 2, 3, and 4, respectively.
      The integrated biological analysis on RNA-Seq data provided substantial of bio
      molecular related to the HCC development. miR-147b, SP1, and Riboflavin were the
      subtype-related regulator/drug for HCC. The study about the big data of HCC RNA
      Seq data reveals the intrinsic gene expression pattern of the tumor, which
      provides a novel perspective to understand the heterogeneity of pathogenesis in
      HCC tumorigenesis.

PMID- 29322796
TI  - Pitfalls of Contrast Enhanced Ultrasound (CEUS) in determination of breast tumor
      biological dignity.
AB  - The aim of this prospective study was to identify characteristics of breast
      lesions on contrast enhanced ultrasound (CEUS) that can be a source of diagnostic
      ambiguity and cause under- or overestimation of examined breast lesions. 215
      women (range 23-76 y., mean age 53.16 y) with 215 breast lesions were examined by
      B-mode ultrasound, followed by CEUS and core biopsy. CEUS parameters: degree of
      opacification, character of washout and preliminary CEUS result (suspicious, non
      suspicious, uncertain) were subsequently correlated with histopathological
      outcomes. Observed qualitative variables, CEUS results and their analysis with
      respect to histological type were evaluated using Pearson chi2 square test,
      p<0.05 was statistically significant. Differences in mean lesion size, mean age
      of patients, mean size between groups (malignant/benign) with respect to CEUS
      result were evaluated by t-test. 215 tumors, 116 (53.93%) benign and 99 (46.05%)
      malignant lesions. 17 (14.66%) benign and 15 (15.15%) malignant lesions expressed
      atypical washout, 5 (4.31%) benign lesions had early washout and 38 (38.38%) had
      continuous washout (p<0.0001). 56 (48.28%) benign and 55 (55.56%) malignant
      lesions had middle degree of opacification, 19 (16.38%) benign had high and 5
      (5.05%) malignant lesions low degree of opacification (p<0.0001). Finally, 38
      (32.72%) benign and 20 (20.20%) malignant were marked CEUS uncertain. As risk
      lesions are considered fibroadenomas, fibrocystic lesions, papillomas and low
      grade DCIS or invasive breast tumors, especially lesions smaller than 10
      mm.Identification of CEUS pitfalls with respect to problematic histopathologic
      entities can reduce the risk of misdiagnosis and improve further management of
      breast lesions.

PMID- 29322795
TI  - Analysis of DNA methylation and microRNA expression in NUT (nuclear protein in
      testis) midline carcinoma of the sinonasal tract: a clinicopathological,
      immunohistochemical and molecular genetic study.
AB  - The aim of this study was a detailed clinicopathological investigation of
      sinonasal NUT midline carcinoma (NMC), including analysis of DNA methylation and
      microRNA (miRNA) expression. Three (5%) cases of NMC were detected among 56
      sinonasal carcinomas using immunohistochemical screening and confirmed by
      fluorescence in situ hybridization. The series comprised 2 males and 1 female,
      aged 46, 60, and 65 years. Two tumors arose in the nasal cavity and one in the
      maxillary sinus. The neoplasms were staged pT1, pT3, and pT4a (all cN0M0). All
      patients were treated by radical resection with adjuvant radiotherapy. Two
      patients died 3 and 8 months after operation, but one patient (pT1 stage; R0
      resection) experienced no evidence of disease at 108 months. Microscopically, all
      tumors consisted of infiltrating nests of polygonal cells with vesicular nuclei,
      prominent nucleoli and basophilic cytoplasm. Abrupt keratinization was present in
      only one case. Immunohistochemically, there was a diffuse expression of
      cytokeratin (CK) cocktail, CK7, p40, p63, and SMARCB1/INI1. All NMCs tested
      negative for EBV and HPV infection. Two NMCs showed methylation of RASSF1 gene.
      All other genes (APC, ATM, BRCA1, BRCA2, CADM1, CASP8, CD44, CDH13, CDKN1B,
      CDKN2A, CDKN2B, CHFR, DAPK1, ESR1, FHIT, GSTP1, HIC1, KLLN, MLH1a, MLH1b, RARB,
      TIMP3, and VHL) were unmethylated. All NMCs showed upregulation of miR-9 and
      downregulation of miR-99a and miR-145 and two cases featured also upregulation of
      miR-21, miR-143, and miR-484. In summary, we described three cases of sinonasal
      NMCs with novel findings on DNA methylation and miRNA expression, which might be
      important for new therapeutic strategies in the future.

PMID- 29322797
TI  - Effectiveness of nanoparticle albumin-bound paclitaxel plus carboplatin in non
      small lung cancer patients with malignant pleural effusion.
AB  - Malignant pleural effusion (MPE) is a common complication occurring in cancer
      patients, and its management affects the prognosis of these patients. Preclinical
      and clinical studies have reported that treatment with nanoparticle albumin-bound
      paclitaxel (nab-paclitaxel) plus carboplatin (CBDCA) is effective against
      intraperitoneal malignant tumors. To investigate the effectiveness of nab
      paclitaxel plus CBDCA therapy for MPEs arising in patients with non-small cell
      lung cancer (NSCLC), we retrospectively analyzed the clinicopathological
      characteristics of 40 patients with stage IIIb or IV NSCLC who were treated with
      nab-paclitaxel plus CBDCA from 2013 to 2016. Out of 26 patients with MPEs who
      were treated with nab-paclitaxel plus CBDCA in this study, 21 patients (80.8%)
      had effective responses in MPEs; 6 of 21 patients exhibited complete responses
      (23.1%) and 15 of 21 had partial responses (57.7%). Kaplan-Meier survival curves
      and log-rank tests to evaluate the effectiveness of nab-paclitaxel plus CBDCA
      therapy against MPEs showed longer median progression-free survival (323 days vs.
      26 days; p=0.009) and overall survival (not reached vs. 199 days; p=0.047) in
      patients with complete responses compared with those who achieved no response.
      There were no statistical differences between therapeutic effects on MPEs and
      those on systemic lesions. Nab-paclitaxel plus CBDCA therapy may be a preferred
      therapeutic option for patients with NSCLC who experience MPEs, and its
      effectiveness in treatment of MPEs may need to be evaluated separately from its
      therapeutic responses in systemic lesions.

PMID- 29322798
TI  - PD-L1 expression can be regarded as prognostic factor for survival of non-small
      cell lung cancer patients after chemoradiotherapy.
AB  - Inoperable locally advanced non-small cell lung cancer (LA NSCLC) is treated with
      concurrent or sequential chemotherapy (ChT) and radiation therapy (RT). Survival
      rates with this treatment remains poor, reported 5-year survival is about 15%.
      New treatment strategies, including immunotherapy with programmed death ligand-1
      (PD-L1) check point inhibitors are being investigated. The clinical significance
      of PD-L1 expression in tumor samples from patients with inoperable LA NSCLC who
      underwent concurrent chemoradiotherapy (CRT) in our institution between 2005 and
      2010 was evaluated. The expression of PD-L1 was correlated with clinical and
      pathological parameters and outcome of treatment. We analysed 107 patients
      treated with concurrent CRT. Only 43 patients (36 males and 7 females) had
      sufficient tissue for immunohistochemical (IHC) staining. PD-L1 expression was
      demonstrated in 7 tumors. No statistical significant differences in patient
      characteristics, including age, smoking status and gender, were found according
      to the PD-L1 expression. After a median follow up of 103.6 months, median
      progression free survival (PFS) was 19.9 months in patients without and 10.1
      months in patients with PD-L1 expression (p=0.006). Median overall survival (OS)
      was 28.4 and 12.1 months for PD-L1 negative and PD-L1 positive patients,
      respectively (p=0.012).In conclusions, PD-L1 expression was negative prognostic
      factor for PFS and OS after concurrent CRT in LA NSCLC. As only small number of
      patients had enough tissue for the IHC testing, no firm conclusions could be made
      and further investigation is warranted.

PMID- 29322799
TI  - Predictors and prognostic implications of clinical decisions in patients with
      primary high-risk non-muscle-invasive bladder cancer - results of a cross country
      retrospective study.
AB  - Adjuvant diagnostic and therapeutic procedures are available to reduce the risk
      of recurrence or progression in patients with high-risk non-muscle-invasive
      bladder cancer (NMIBC). However, their indications and efficacy remain a matter
      of debate. The aim of this study was to analyze therapeutic decisions in patients
      with primary high-risk NMIBC and to analyze the adherence to clinical guidelines
      in this field.545 consecutive patients, aged a median of 70.3 years, diagnosed
      with primary high-risk NMIBC in thirteen urological institutions, were enrolled
      into this retrospective study. Diagnostic and therapeutic decisions after
      transurethral resection (TUR) were recorded, and predictive factors were
      analyzed.Restaging TUR was offered to 260 patients (47.7%), up-front intravesical
      Bacillus Calmette-Guerin (BCG) therapy to 74 patients (13.6%), immediate radical
      cystectomy to 38 patients (7.0%), and intravesical chemotherapy with the
      maintenance therapy to 12 patients (2.2%). No additional procedure was performed
      in 161 patients (29.5%). The strongest predictive factor for restaging TUR was G3
      or high-grade cancer (RR 1.68, p<0.01), for upfront BCG therapy it was carcinoma
      in situ (RR 3.20, p=0.01), for immediate cystectomy it was stage T1 tumor (RR
      3.71, p<0.01), for no additional procedures it was G2 or low-grade cancer (RR
      2.18, p<0.01).Clinical management of patients with high-risk NMIBC is suboptimal
      and not standardized. As this can directly influence patients' survival, urgent
      improvement of urological care in this field should be considered.

PMID- 29322800
TI  - USF1 gene polymorphisms may associate with the efficacy and safety of
      chemotherapy based on paclitaxel and prognosis in the treatment of ovarian
      cancer.
AB  - This study was supposed to investigate the correlation between the functional
      single nucleotide polymorphisms (SNPs) (rs2516839 and rs3737787) in USF1 gene and
      the efficacy and safety of paclitaxel-based chemotherapy and prognosis in the
      treatment of ovarian cancer (OC). In total 100 OC patients were selected and
      divided into the sensitive group and the resistantgroup according to the tumor
      response to paclitaxel-based chemotherapy after surgery, and the incidence of
      observed and recorded toxic reaction. Polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP) method was applied to test the
      polymorphisms of rs2516839 and rs3737787 in USF1 gene after extraction of DNA.
      The correlation between USF1 gene polymorphisms and paclitaxel-based chemotherapy
      resistance was analyzed using Logistic regression analysis. Stratified analysis
      was used to test the incidence of toxic reaction in OC patients. Cox proportional
      hazard model was adapted to make a multiple-factor survival analysis. Significant
      differences exhibited in the genotype and the allele frequencies of rs2516839
      between the sensitive and resistant groups, which showed no obvious difference in
      the genotype and allele frequencies of rs3737787. OC patients carrying the GA+AA
      genotype had higher incidence of serious toxic reaction than those carrying the
      GG genotype. Physical status score, tumor type, maximum tumor diameter and
      rs2516839 were the independent risk factors for the prognosis of OC patients.
      Taken together, our results suggest that the rs2516839 polymorphism in USF1 gene
      may associate with the efficacy and safety of paclitaxel-based chemotherapy and
      prognosis in the treatment of OC.

PMID- 29322778
TI  - Using Genome Sequence to Enable the Design of Medicines and Chemical Probes.
AB  - Rapid progress in genome sequencing technology has put us firmly into a
      postgenomic era. A key challenge in biomedical research is harnessing genome
      sequence to fulfill the promise of personalized medicine. This Review describes
      how genome sequencing has enabled the identification of disease-causing
      biomolecules and how these data have been converted into chemical probes of
      function, preclinical lead modalities, and ultimately U.S. Food and Drug
      Administration (FDA)-approved drugs. In particular, we focus on the use of
      oligonucleotide-based modalities to target disease-causing RNAs; small molecules
      that target DNA, RNA, or protein; the rational repurposing of known therapeutic
      modalities; and the advantages of pharmacogenetics. Lastly, we discuss the
      remaining challenges and opportunities in the direct utilization of genome
      sequence to enable design of medicines.

PMID- 29322801
TI  - Paraoxonase activity in sera of patients with non-alcoholic fatty liver disease.
AB  - The results of our study showed significantly decreased levels of PON1 in
      patients with chronic liver diseases (controls 185 +/- 14 U/l, NAFLD 160 +/- 15
      U/l, chronic hepatitis 99 +/- 18 U/l, cirrhosis 52 +/- 11 U/l). There were
      significant correlations of PON activities with standard liver function tests
      (Tab. 1, Ref. 5).

PMID- 29322802
TI  - Cardiac telocytes as principal interstitial cells for myocardial reparation and
      regeneration after infarction - our hope.
AB  - According to our knowledge, this is the first research experiment that focuses on
      the study of the distribution of c-kit positive cells at the sites of myocardial
      infarction in human hearts (Fig. 3, Ref. 16).

PMID- 29322804
TI  - Conservative management of biopsy confirmed high-grade squamous intraepithelial
      lesions.
AB  - OBJECTIVES: Follow-up of women with biopsy-confirmed CIN2+ who were either
      treated immediately with LLETZ or managed conservatively to determine the rates
      of patients back on routine screening programme after a median of three years in
      two groups. METHODS: In this retrospective study, 310 patients were involved who
      had undergone biopsy with result of CIN2+ between January 2011 and December 2014.
      Depending on the management, i.e. based on whether cytology and colposcopy follow
      up or immediate treatment were performed, they were divided in two groups. Then
      the number of patients back on routine screening up to 15/2/2016 as well as the
      results of last cytology were compared within both groups. RESULTS: A total of
      310 women at average age of 30 years met the inclusion criteria. Of them, 230 (74
      %) had immediate treatment whereas 80 (26 %) were managed conservatively. There
      were no statistically significant demographic differences between the two groups.
      The mean time of follow up was 1.091 days (2.98 years). The patients managed
      conservatively required more follow-up visits at colposcopy clinic (p<0.001). The
      last documented cytology in the immediate treatment group was negative in 93 %
      and low-grade/borderline in 7 % of patients, while in the conservative management
      group, it was negative in 84 %, low-grade/borderline in 15 % and high-grade in 1
      % of patients (p = 0.015). Overall, the proportions of patients who are back on
      routine screening recall are 96 % and 87.5 % for the immediate treatment and
      conservatively managed groups, respectively (p=0.022). CONCLUSION: The
      conservative management of high-grade CIN with cytology and colposcopic follow up
      is an OPTION in selected group of patients, but it cannot be routinely
      recommended (Tab. 2, Ref. 20).

PMID- 29322803
TI  - Is the prevalence of the medication-related osteonecrosis of the jaws
      underestimated, evaluation in oncological and non-oncological disease.
AB  - OBJECTIVES: The purpose of this study was to evaluate the prevalence of
      medication-related osteonecrosis of the jaw in Slovak population and compare the
      literature findings, whether the prevalence of MRONJ is underestimated.
      BACKGROUND: Antiresorptive drugs significantly increase quality of life, although
      during therapy, or in post-treatment period, osteonecrosis of the jaws might
      occur as a severe adverse effect. Medication-related osteonecrosis of the jaws
      (MRONJ) is a severe problem that has been observed in the past few years.
      METHODS: This multi-centric study evaluates the prevalence in Slovak population,
      assesses the values from 4 largest centres of maxillofacial surgery in Slovakia
      (1166 patients with MRONJ) and provides the comparison of literature review.
      RESULTS: Between 2010-2015, there was increasing number of newly diagnosed
      patients with MRONJ (1166 overall MRONJ patients) annually, except 2012 (mean
      growth of 123.88 %). This finding was supported by a statistical analysis of the
      rising tendency of prevalence in literature, where there was a significant
      difference in prevalence of non-oncologic patients before and after 2010 t(15) =
      2.725, p = 0.016. The 6-year prevalence was 1.34 % in population with
      antiresorptive drugs intake, for osteoporosis 0.47 %, for breast cancer 4.10 %,
      prostate cancer 3.99 % and multiple myeloma 21.26 %. CONCLUSION: This study
      considers that there is a significant rising tendency of MRONJ in non-oncological
      patients, what could be caused by underestimation of the risk for development
      MRONJ in these patients. There should be a better cooperation and information
      among dentists and doctors indicating the antiresorptive treatment and strong
      emphasis on primary prevention before the initial treatment even in non
      oncological patients (Tab. 5, Fig. 7, Ref. 69).

PMID- 29322805
TI  - Wound infections after median sternotomy treated by VAC therapy, summary of
      results, and risk factor analysis.
AB  - INTRODUCTION: The aim of this study is to summarize results and analyze risk
      factors for the development of wound infection in heart surgery patients after
      median sternotomy. METHOD: In this retrospective analysis with assessment of
      multiple risk factors, we examined 143 patients with infection after median
      sternotomy treated with VAC therapy from total of 4,650 patients operated in our
      department from 2012 to 2015. RESULTS: Total of 143 patients developed
      significant SSI treated by VAC therapy following cardiac surgery. Of these, only
      14 patients developed DSWI and one patient was diagnosed with suspected
      osteomyelitis. BMI, female gender, and use of BIMA proved to be statistically
      significant risk factors in our study (p < 0.001). The acuteness of operations
      did not have a statistically significant effect. However, it had a significant
      effect on the severity of infection (p < 0.01). The severity of infection proved
      to be a significant prognostic factor for patients' outcome (p < 0.01).
      CONCLUSION: In our study, BMI, female gender, and use of BIMA (bilateral internal
      mammary artery) in patients with DM were predictors for the development of SWI.
      The acuteness of operation did not have a statistically significant effect.
      However, it had a statistically significant effect on the severity of infection
      (Tab. 3, Ref. 30).

PMID- 29322806
TI  - Periodontitis aggravates kidney damage in obese mice by MMP2 regulation.
AB  - OBJECTIVE:   To investigate the effect of periodontitis on the development of
      kidney damage in obese mice and its possible mechanism. METHODS:   C57 BL/6J mice
      were fed high-fat (HF) or low-fat (LF) diet and then divided into four groups: 
      obesity with periodontitis (HFP), obesity without periodontitis (HFC), normal
      mice with periodontitis (LFP) and normal mice without periodontitis (LFC). Serum
      indicators of renal function, namely serum total protein (TP), albumin (ALB),
      creatinine (Cr) and blood urea nitrogen (UREA) were measured. The
      histopathological examination of kidney tissues was performed. The expressions of
      transforming growth factor-beta1 (TGF-beta1), matrix metalloproteinase-2 (MMP2)
      and tissue inhibitors of metalloproteinases-1 (TIMP1) were detected by
      immunohistochemistry and real time RT-PCR. RESULTS:   Obesity decreased TP and
      ALB, and increased serum Cr and UREA levels in normal and periodontitis mice
      groups, as well as induced glomerular and tubulointerstitial pathologic changes.
      Tubulointerstitial fibrosis was more severe in HFP group. In obese mice,
      periodontitis caused the downregulation of MMP2, and upregulation of TIMP1 and
      TGF-beta1 at transcriptional and translational levels. CONCLUSIONS:   In obese
      mice, periodontitis may aggravate pathological changes in the kidney. The
      possible mechanism might lie in downregulation of MMP2 and upregulation of MMP
      inhibitor, TIMP1, and TGF-beta1 (Tab. 1, Fig. 4, Ref. 16).

PMID- 29322807
TI  - Chronic postsurgical pain in mixed surgical population. Does an acute pain
      service make a difference?
AB  - OBJECTIVES: To investigate the influence of an Acute Pain Service (APS) on the
      incidence of chronic postsurgical pain (CPSP). To assess the acute pain intensity
      as a risk factor for CPSP. The impact of an APS on the incidence of CPSP has not
      yet been studied. METHODS: Retrospective questionnaire given to randomized
      cohorts study, performed in two hospitals - Hospital A with an APS and Hospital B
      without such service. 1444 patients underwent eight different surgical procedures
      in both hospitals within one year, 175 patients from each hospital were
      randomized. RESULTS: 208 questionnaires were analysed. There was a significant
      difference in acute pain intensity in the first 24 hours after surgery. The
      difference of CPSP incidence between hospitals was not significant (Hospital A
      nine patients (8.6 %), Hospital B sixteen patients (15.5 %). The patients with
      CPSP experienced significantly more intensive pain in the first 24 hours and at
      discharge than patients without CPSP regardless of the hospital. CONCLUSION: The
      study did not demonstrate the incidence of CPSP was lower in the hospital with an
      APS despite the lower postoperative pain scores. However there was a noticeable
      trend toward higher incidence of CPSP in the hospital without an APS. The study
      demonstrated that APS decreases intensity of an acute postoperative pain and
      acute pain intensity is a risk factor for CPSP incidence (Tab. 5, Ref. 27).

PMID- 29322808
TI  - Effects of epidermal growth factor on reduction of the formation of thrombus and
      vessel wall healing in an experimental rat model.
AB  - OBJECTIVES: The aim of the current study was to investigate the synergistic
      effects of epidermal growth factor (EGF) and Enoxaparin in thrombus resolution.
      METHOD: Forty rats were divided into five groups (n = 8/group). Thrombosis was
      induced in all groups except the Sham group. Group 1: Sham; Group 2: Phosphate
      buffered saline; Group 3: Enoxaparin; Group 4: EGF; Group 5: EGF+Enoxaparin. The
      treatments were applied 2 hours preoperatively, then postoperatively at 48 hours.
      Rats were sacrificed 7 days after the 2nd injection. Tissue samples were examined
      with hematoxylin-eosin, trichrome, vascular endothelial growth factors (VEGF),
      von Villebrand factor (VWF), CD34 and CD68 for histopathological and
      immunohistochemical analyses. RESULTS: Neovascularisation, recanalization and
      macrophage accumulation were statistically significantly higher in the
      EGF+Enoxaparin group than the other groups (p < 0.05), and the volume of thrombus
      was determined to be significantly lower. Recanalization was found to be higher
      in the Enoxaparin group than in the other groups. As for the thrombus resolution,
      statistically significant regress in the EGF+Enoxaparin group (p < 0.05) compared
      to the other groups was found. Immunohistochemical antibodies were statistically
      higher in the EGF+Enoxaparin group than in the other groups (p < 0.05).
      CONCLUSION: The results of this study demonstrate that concomitant use of EGF and
      Enoxparin has a synergistic effect and contributes significantly to thrombus
      resolution (Fig. 10, Ref. 35).

PMID- 29322809
TI  - Effects of 2100 MHz radio frequency radiation on ductus epididymis tissue in
      rats.
AB  - PURPOSE: The use of mobile phones is widespread since the beginning of 1990s. A
      great debate exists about the possible damage that the Radio Frequency - RF
      radiation from mobile phones exerts on different organs. The objective of this
      study was to investigate the possible histopathological effects of 2100 MHz RF
      radiation on rat ductus epididymis tissue using a light microscopy and
      immunohistochemical method after one or two month exposure. MATERIALS AND
      METHODS: The study was performed on 36 adult Wistar albino rats. 2100 MHz RF
      radiation was used with a specific absorption rate (SAR) of 0.36 W/kg for 30
      min/day, 6 days per week for one or two months. There were 3 groups (n = 6 for
      each group): one month RF exposed group, two months RF exposed group, and the
      control group. RESULTS: At the end of the study, the structural changes in ductus
      epididymis tissue were evaluated. In both 2100 MHz RF exposed groups, the rat
      ductus epididymis sperm were not observed in some channels, a reduction in sperm
      density in some of the channels drew an attention. The loss of connective tissue
      and edematous areas were observed in cross channel interstitial connective
      tissue. In addition, it was observed that vascularization was highly increased
      with respect to the control group in cross-channel interstitial connective
      tissue. CONCLUSION: 2100 MHz RF exposure resulted in some structural changes in
      the male genital ducts of rats (Tab. 1, Fig. 5, Ref 20).

PMID- 29322810
TI  - Therapeutic hypothermia and myocardium in perinatal asphyxia: a microvolt T-wave
      alternans and Doppler echocardiography study.
AB  - OBJECTIVES: This is the first study evaluating the predictive value of myocardial
      performance on arrhythmia and mortality via tissue-Doppler and microvolt T-wave
      alternans in infants with hypoxic-ischemic encephalopathy treated with
      therapeutic hypothermia-rewarming. METHODS: The study included 23 term newborns
      having criteria for hypoxic-ischemic encephalopathy, and 12 controls. Tissue
      Doppler imaging and T-wave alternans were performed in the first six hours after
      birth in patients from both groups and after hypothermia-rewarming treatment on
      the fifth day. RESULTS: The basal T-wave alternans values were higher in patients
      in lead aVF(p < 0.001) which also correlated with existing acidemia (r = 0.517; p
      = 0.012). Basal T-wave alternans and post-treatment values of patients were
      compared in leads V1 (p < 0.001) and aVF (p < 0.001); a significant decrease was
      found on the fifth day. Moreover, right ventricle diastolic diameter and
      estimated systolic pulmonary artery pressure of patients in the first 6 hours
      were higher (p = 0.03, p < 0.001, respectively). Although, the ejection fraction
      of patients did not decrease, basal values of left and right ventricular systolic
      and diastolic functions were lower initially, and increased significantly after
      treatment. CONCLUSION: The global cardiac functions and myocardial performance of
      newborns with hypoxic-ischemia might be improved with therapeutic hypothermia
      which can be determined by using T-wave alternans and tissue-Doppler
      measurements. However, further studies are needed to assess whether these
      measurements are prognostic in determining the myocardial dysfunction and
      arrhythmias (Tab. 2, Fig. 3, Ref. 26).

PMID- 29322811
TI  - Establishment of reverse transcription polymerase chain reaction assay for
      simultaneous detection of human parainfluenza virus types 1 to 4 in children with
      influenza like illnesses.
AB  - OBJECTIVES: The aim of this study was to develop an in-house multiplex reverse
      transcription polymerase chain reaction (mRT-PCR), which can recognize HPIV1-4 in
      clinical samples. BACKGROUND: Human parainfluenza virus (HPIV) is one of the
      major causes of viral respiratory infections and can affect people at any age,
      especially infants and young children. METHODS: Four sets of specific primers
      targeting conserved areas of hemagglutinin-neuraminidase (HN) genes of HPIV1-4,
      were designed and tested with type-related plasmid controls. Specificity and
      sensitivity of mPCR were tested. One-step mRT-PCR was set up using a viral panel
      containing 10 respiratory viruses, including HPIVs. One hundred nasopharyngeal
      samples of respiratory infection patients were tested using the set One-step mRT
      PCR. RESULTS: The specificity of set mPCR for HPIV1-4 using plasmid positive
      controls was proved and reaction sensitivity was measured. The specificity of set
      mRT-PCR was confirmed and 4 and 5 out of 100 clinical samples were HPIV1 and
      HPIV2 positive, respectively. CONCLUSION: The developed one-step mRT-PCR in this
      study is an effective and specific assay for clinical diagnosis of HPIV1 to 4
      (Tab. 1, Fig. 6, Ref. 28).

PMID- 29322812
TI  - Adjustment to finger amputation and silicone finger prosthesis use.
AB  - PURPOSE: Finger amputations are the most common amputations of upper limbs. They
      influence hand function, general functioning and quality of life. One of the
      possibilities for rehabilitation after finger amputation is fitting a silicone
      finger prosthesis. We wanted to evaluate the adjustment to amputation and
      prosthesis use in patients after finger amputation. METHODS: We included 42
      patients with partial or complete single or multiple finger amputation of one
      hand who visited the outpatient clinic for prosthetics and orthotics at our
      institute and received a silicone prosthesis. We assessed their adjustment to
      amputation and prosthesis with the Trinity Amputation and Prosthesis Experience
      Scales (TAPES). RESULTS: Most of the patients (28, 67%) had a single finger
      amputated. The average scores on all TAPES subscales (except adjustment to
      limitation) were above 50% of the maximum possible score. On average, the scores
      were the highest on the general adjustment and satisfaction with the prosthesis
      subscales. CONCLUSIONS: Silicone prostheses for finger amputation of upper limb
      play an important role in the process of adaptation to amputation. They offer
      aesthetically satisfying results and alleviate social interactions, which
      influences overall quality of life. Implications for Rehabilitation Silicone
      prostheses for finger amputation of upper limb offer an aesthetically satisfying
      result and alleviate problems with social interactions. Their influence on hand
      function is not optimal, but the prosthesis improves the amputee's quality of
      life.

PMID- 29322813
TI  - Opioid drug poisonings in Ohio adolescents and young adults, 2002-2014.
AB  - CONTEXT: Opioids represent a drug class that adolescents and young adults
      intentionally misuse and abuse. When taken on their own or with other substances
      in this manner, opioids pose an increased risk of overdose and potential death.
      OBJECTIVE: To determine trends of opioid drug poisonings among adolescents and
      young adults in Ohio from 2002 to 2014 using Poison Control Center (PCC) data.
      METHODS: Data were obtained from Ohio PCCs from 2002 to 2014 for opioid drug
      poisonings amongst 10-29 year olds. Trends were evaluated with Poisson
      regression. Ohio counties with higher opioid drug poisoning rates were identified
      using age-adjusted resident population estimates. Chi-square tests were conducted
      to compare these county rates to the Ohio rate. RESULTS: Both unintentional and
      intentional Ohio PCC opioid drug poisonings peaked in 2009, and there were
      significant declines through 2014. Almost 40% of intentional opioid drug
      poisonings were for young adults aged 18-24 years. Suspected suicide poisonings
      were 64.9% female, misuse poisonings were 54.5% male, and abuse poisonings were
      60.1% male. Commonly reported substances included tramadol, heroin, and
      acetaminophen combinations with hydrocodone or oxycodone. Benzodiazepines and
      ethanol were the most common substances reported in conjunction with opioids. The
      top four Ohio counties with significantly higher opioid drug poisoning rates than
      the state average in 2014 were Hamilton, Mahoning, Butler, and Fairfield.
      CONCLUSION: This study enhances the understanding of Ohio's opioid epidemic so
      that future prevention efforts and legislation can better target needed
      resources. Both males and females would benefit from opioid education early in
      their lives.

PMID- 29322814
TI  - Contraceptive counselling and care: a personalized interactive approach.
AB  - AIM: Various studies have shown deficiencies and gaps in contraceptive
      counselling and care (CCC) in Europe as well as globally. These deficiencies
      include the lack of personalized communication integrating the individual woman's
      needs and her biopsychosocial profile into the interaction with the Health Care
      Professional (HCP). OBJECTIVE: Based on the standards summarized in the
      literature and based on the concept of interactive shared decision, we developed
      a structured approach as a proposal for CCC. RESULT: Integrating principles of
      patient-centred communication and trustful relationship, we propose a stepwise
      process of interactive counselling and care allowing women to express their needs
      and priorities, then help the HCP by taking into the account the biopsychosocial
      profile of the woman to exclude methods together with the woman which do not
      correspond to her needs or which are contraindicated; then look for additional
      benefits of contraceptive methods for the individual woman to finally come to a
      shared transparent decision. CONCLUSION: This personalized interactive counseling
      approach may serve as an orientation for HCPs to find their individual way to
      tailor contraception to the individual woman.

PMID- 29322816
TI  - Correction to: Garratt and Turner, Progesterone for preventing pregnancy
      termination after initiation of medical abortion with mifepristone.

PMID- 29322815
TI  - Bioinformatic analysis of PFN2 dysregulation and its prognostic value in head and
      neck squamous carcinoma.
AB  - AIM: This study aimed to identify PFN2 expression profile, its prognostic value
      and the mechanism of its dysregulation in head and neck squamous cell carcinoma
      (HNSC). MATERIALS & METHODS: Bioinformatic analysis was performed using data in
      the Gene Expression Omnibus Datasets, Human Protein Atlas and The Cancer Genome
      Atlas-HNSC. RESULTS: PFN2 was upregulated in HNSC than in normal head and neck
      tissues. High PFN2 expression independently predicted poor overall survival in
      primary HNSC (hazard ratio: 1.548, 95% CI: 1.174-2.042; p = 0.002). Fourteen
      percent of HNSC cases had PFN2 amplification. PFN2 DNA methylation was negatively
      correlated with its mRNA expression (Pearson's r = -0.713). CONCLUSION: High PFN2
      expression might serve as a valuable predictor for poor overall survival of HNSC.
      DNA amplification and hypomethylation might be two mechanisms of PFN2
      dysregulation.

PMID- 29322818
TI  - Evolution of pH buffers and water homeostasis in eukaryotes: homology between
      humans and Acanthamoeba proteins.
AB  - AIM: This study intended to trace the evolution of acid-base buffers and water
      homeostasis in eukaryotes. Acanthamoeba castellanii  was selected as a model
      unicellular eukaryote for this purpose. Homologies of proteins involved in pH and
      water regulatory mechanisms at cellular levels were compared between humans and
      A. castellanii. MATERIALS & METHODS: Amino acid sequence homology, structural
      homology, 3D modeling and docking prediction were done to show the extent of
      similarities between carbonic anhydrase 1 (CA1), aquaporin (AQP), band-3 protein
      and H+ pump. Experimental assays were done with acetazolamide (AZM), brinzolamide
      and mannitol to observe their effects on the trophozoites of  A. castellanii.
      RESULTS: The human CA1, AQP, band-3 protein and H+-transport proteins revealed
      similar proteins in Acanthamoeba. Docking showed the binding of AZM on amoebal
      AQP-like proteins.  Acanthamoeba showed transient shape changes and encystation
      at differential doses of brinzolamide, mannitol and AZM.  Conclusion: Water and
      pH regulating adapter proteins in Acanthamoeba and humans show significant
      homology, these mechanisms evolved early in the primitive unicellular eukaryotes
      and have remained conserved in multicellular eukaryotes.

PMID- 29322817
TI  - Endovascular coil embolization and stenting for the treatment of iatrogenic right
      internal mammary artery injury: A case report.
AB  - A 54-year-old Chinese woman presented with a 10-year history of repeated
      paroxysmal palpitations. She was diagnosed with paroxysmal supraventricular
      tachycardia by 12-lead electrocardiogram and was advised to undergo catheter
      based radiofrequency ablation. During the procedure, a rare complication occurred
      that was diagnosed as a right internal mammary artery penetrating injury. After
      appropriate emergency treatment with arterial embolization and membrane-covered
      stent implantation, the patient was out of immediate danger of haemorrhaging.
      Follow-up computed tomography angiography of the subclavian artery at 3 months
      after she was discharged from hospital revealed stent-graft patency with no
      evidence of in-stent thrombosis or stent stenosis. No problems were observed at
      the 6-month follow-up visit.

PMID- 29322819
TI  - A novel cyclohexenone from Trachyspermum roxburghianum.
AB  - A novel cyclohexenone, roxydienone (1), together with 13 known compounds (2-14),
      were isolated from the seeds of Trachyspermum roxburghianum. The structures of
      these compounds were established on the basis of their 1D and 2D NMR
      spectroscopic data. Compounds 1, 2, 7-9 and 14 showed cytotoxicity against NCI
      H187 cell line while compounds 1 and 9 showed cytotoxicity against KB cell line.
      In addition, only compound 13 showed cytotoxicity against MCF-7 cell line.

PMID- 29322820
TI  - Reevaluation of the Critically Ill Patients With Nonconvulsive Status Epilepticus
      by Using Salzburg Consensus Criteria.
AB  - OBJECTIVE: We aimed to assess the usefulness of the Salzburg Consensus Criteria
      (SCC) for determining the prognosis of critically ill patients with nonconvulsive
      status epilepticus (NCSE). METHODS: We retrospectively reviewed consecutive
      patients with unconsciousness followed up in the intensive care unit (ICU). Three
      clinical neurophysiologists, one of them blinded to clinical and laboratory data,
      reevaluated all EEG data independently and determined NCSE according to SCC. The
      incidence of NCSE and ictal EEG patterns and their relationship to clinical,
      laboratory, neuroradiological, and prognostic findings were assessed. RESULTS: A
      total of 107 consecutive patients with mean age 68.2 +/- 15.3 years (57 females)
      were enrolled in the study. Primary neuronal injury was detected in 59 patients
      (55.7%). Thirty-three patients (30.8%) were diagnosed as NCSE. While authors
      decided to treat 33 patients (30.8%), 32 patients (29.9%) had been treated in
      real-life evaluation. Clinical and EEG improvement were detected in 12 patients
      (11.3%) in real-life treatment group showing correlation with lack of intubation
      and ICU stay related to postsurgical event. Rate of mortality (45.8%) was high
      showing association with systemic-metabolic etiology, severity of coma and
      presence of "plus" modifiers in the EEG. CONCLUSION AND SIGNIFICANCE: Our
      findings suggest that SCC is highly compatible with clinical practice in the
      decision for treatment of patients with NCSE. The presence of "plus" modifiers in
      the EEG was found to be associated with mortality in these patients and was a
      significant marker for the high mortality rate.

PMID- 29322821
TI  - Moderately hypofractionated prostate external-beam radiotherapy: an emerging
      standard.
AB  - Research over recent years has demonstrated that curative external-beam
      radiotherapy can be safely and efficaciously delivered with roughly half the
      number of treatments which was previously considered standard. We review the data
      supporting this change in practice, methods for implementation, as well as
      emerging future directions.

PMID- 29322822
TI  - Assessment of aided language comprehension and use in children and adolescents
      with severe speech and motor impairments.
AB  - There is limited knowledge about aided language comprehension and use in children
      who use aided communication and who are considered to have a relatively good
      comprehension of spoken language. This study's purpose was to assess their aided
      language skills. The participants were 96 children and adolescents who used
      communication aids (aided group) and 73 children and adolescents with natural
      speech (reference group), aged 5 to 15 years. All of the participants who used
      aided communication were regarded by their teachers or professionals as having
      age-appropriate language comprehension. All of the participants completed (a)
      standardized tests of visual perception, non-verbal reasoning, and comprehension
      of spoken language, and (b) tasks designed for this study that measured
      comprehension and production of graphic utterances through communicative problem
      solving. Using their own communication systems, the participants achieved an
      average of 72% correct on the graphic symbol comprehension task items, and 63% on
      the expressive tasks. The participants with natural speech achieved an average of
      88% correct on comprehension items, and 93-96% accuracy on production items. The
      differences between groups were significant on all the tasks and standardized
      tests. There was considerable variation within the group of participants who used
      aided communication, and the results reveal a need to develop instruments with
      norms for aided language competence that can inform the implementation of
      interventions to support aided language development.

PMID- 29322823
TI  - Use of space and behavior of weaned piglets kept in enriched two-level housing
      system.
AB  - In this study, the possibility of introducing an elevated platform to a piglet
      pen was explored as a way of increasing available space and creating functional
      areas. On the platform, nine different manipulable materials were offered. In
      four batches, 40 weaned piglets were kept for five weeks in the two-level pen.
      Video recordings were taken two days per week. In the afternoon, more piglets
      were on the platform than in the morning or at night (7.2 +/- 0.1 vs. 4.9 +/- 0.1
      vs. 0.6 +/- 0.1 piglets/5 minutes; p < .05). The area under the platform was
      preferred more in the morning and at night than in the afternoon (18.5 +/- 0.1
      vs. 21.6 +/- 0.2 vs. 12.5 +/- 0.1 piglets/5 minutes; p < .05). Up to 36 piglets
      were counted there simultaneously, mainly in the recumbent position. On and under
      the platform, air velocity and ammonia concentration were within the recommended
      ranges. The study concluded that a two-level pen is a feasible option to increase
      space allowance and to create functional areas in a piglet pen.

PMID- 29322825
TI  - Blood Glucose Monitoring Data Should Be Reported in Detail When Studies About
      Efficacy of Continuous Glucose Monitoring Systems Are Published.
AB  - Recently, two clinical trials about a "sensor-based flash glucose monitoring
      system" and its efficacy in reducing time in hypoglycemia were published.
      Interestingly, patients spent more time at low glucose concentrations in these
      studies than in other studies related to the efficacy of real-time continuous
      glucose monitoring (rtCGM). Although it is possible that the study populations
      differed from those in other studies, another potential explanation is that the
      CGM system used in these two studies had a negative glucose measurement bias.
      Such a negative bias was reported in recent literature, suggesting that the CGM
      system may inaccurately indicate hypoglycemia. Reporting blood glucose monitoring
      data would help to interpret the CGM data at least in the context of time spent
      in various glucose ranges as a parameter with which quality of diabetes therapy
      is measured.

PMID- 29322824
TI  - Detection and analysis of variants of JC polyomavirus in urine samples from HIV-1
      infected patients in China's Zhejiang Province.
AB  - Objectives Human JC polyomavirus (JCPyV) infection has an increased risk of
      developing progressive multifocal leukoencephalopathy (PML). Different JCPyV
      subtypes differ in the virulence with which they cause PML. Currently, the JCPyV
      infection status and subtype distribution in patients with human immunodeficiency
      virus-1 (HIV-1) in China are still unclear. This study aimed to investigate the
      epidemiology and subtype distribution of JCPyV in HIV-1-infected patients in
      China. Methods Urine samples from 137 HIV-1-infected patients in Zhejiang
      Province in China were tested for the presence of JCPyV DNA. The detected VP1
      sequences were aligned and analysed using BioEdit and MEGA software. Results
      Among urine samples from HIV-1-infected patients, 67.2% were positive for JCPyV
      DNA (92/137). Primarily, the type 7 strains of JCPyV were detected, among which
      45.5% (15/33) were subtype 7A, 30.3% (10/33) were 7B, and 24.2% (8/33) were 7C.
      Six nucleotide mutations, as well as one amino acid substitution, were isolated
      from the patients. Conclusions Urine samples from HIV-1-infected patients from
      Zhejiang Province show a high JCPyV infection rate. The most common JCPyV strains
      are subtypes 7A, 7B, and 7C.

PMID- 29322826
TI  - Evaluation of the eighth American Joint Committee on Cancer staging system for
      malignant melanoma of the skin.
AB  - AIM: To validate the changes among the American Joint Committee on Cancer (AJCC)
      eighth staging system for cutaneous melanoma. METHODOLOGY: Surveillance,
      Epidemiology and End Results database (2004-2014) was queried. Kaplan-Meier
      survival estimates were evaluated according to both AJCC seventh and eighth
      systems. RESULTS: Overall survival was assessed according to the two editions and
      p-values for overall trend were significant (p < 0.001) for all scenarios.
      Notably for pathologically staged patients, the mean survival for stage IIC was
      lower than that for stage IIIA and IIIB. Likewise, among clinically staged
      patients the mean survival for stage IIC was lower than that for stage III (these
      findings were identical among both editions). CONCLUSION: AJCC eighth system
      holds comparable performance to AJCC seventh system.

PMID- 29322828
TI  - Population survey and management strategies of free-roaming dogs (Canis
      familiaris) on Saipan, Commonwealth of the Northern Mariana Islands.
AB  - The island of Saipan, Commonwealth of the Northern Mariana Islands, is populated
      by free-roaming dogs who were introduced during World War II. The local nonhuman
      animal control agency manages this population; however, the demographic
      information and public perception of this population remain unknown. To
      characterize the free-roaming dog population, an island-wide survey on Saipan was
      conducted. Photographic, mark-recapture data were used to estimate the population
      size per land type. Age, sex, sociality, and behavior per land type were
      documented and associations between these variables were tested using G tests.
      The effects of land type and urbanization on dog abundance were also analyzed.
      Lastly, in-person surveys provided data on the public perception of free-roaming
      dogs. Four main findings are reported: (a) The population size of free-roaming
      dogs on Saipan is estimated at 21,316. (b) Most dogs encountered were sentry
      adults. (c) Dog abundance increased with urbanization level and was highest in
      urban areas. (d) The public perceived free-roaming dogs as a health concern and
      suggested the implementation of leash laws and sheltering initiatives. This
      article discusses potential and existing population management strategies for
      free-roaming dogs on Saipan.

PMID- 29322829
TI  - Chemical composition and antimicrobial activity of the essential oils from
      flowers and leaves of Grindelia integrifolia DC.
AB  - Essential oils from flowers and leaves of Grindelia integrifolia DC. were
      investigated for the first time in terms of chemical composition and
      antimicrobial activity. The GC-FID/MS analysis allowed for the identification of
      58 and 72 volatiles, comprising 92.4 and 90.1% of the oils, respectively. The
      major components of the flower oil were alpha-pinene (34.9%) and limonene
      (13.1%), while myrcene (16.9%), spathulenol (12.3%), beta-eudesmol (11.9%) and
      limonene (10.1%) dominated among the leaf volatiles. The antimicrobial activity,
      evaluated against 12 selected bacteria and fungus, was found moderate, with the
      strongest effect of both oils observed against C. albicans (MIC = MBC: 0.63 and
      0.31 mg/mL for flower and leaf oil, respectively).

PMID- 29322827
TI  - Hypofractionated volumetric modulated arc therapy in ductal carcinoma in situ:
      toxicity and cosmetic outcome from a prospective series.
AB  - OBJECTIVE: Hypofractionated radiotherapy in early stage breast cancer is an
      effective adjuvant treatment, but there is a lack of randomized data for patients
      with ductal carcinoma in situ (DCIS). The aim of this study is the evaluation of
      skin toxicity and cosmesis, and early clinical outcome of DCIS patients enrolled
      in an institutional Phase II trial of hypofractionated breast irradiation.
      METHODS: 137 DCIS patients were enrolled in the trial. All patients underwent
      volumetric modulated arc therapy (VMAT) to the whole breast with a total dose of
      40.5 Gy in 15 fractions over 3 weeks, without tumour bed boost. Acute and late
      skin toxicities were recorded. Cosmetic outcomes were assessed as excellent/good
      or fair/poor. Early clinical outcome was reported. RESULTS: Median age was 58
      y.o. (range 30-86). The median follow-up time was 22 months (range 6-45). At the
      end of the radiotherapy, skin toxicity was grade G1 in 56% of the patients, G2 in
      15%, no patients presented G3 toxicity. In the range of 3-9 months of follow-up,
      the skin toxicity was G1 in 28% of patients, no G2-G3 cases; cosmetic outcome was
      good/excellent in 95% of patients. In the follow-up interval of 9-24 months, the
      skin toxicity was G1 in 12% of patients, no G2-G3 toxicity; cosmetic outcome was
      good/excellent in 96% of patients. After an early evaluation of clinical
      outcomes, 5 patients (3.6%) presented an in-breast recurrence. CONCLUSION:
      Hypofractionated radiotherapy using VMAT is a viable option for DCIS. A longer
      follow-up is needed to assess clinical outcomes and late toxicity. Advances in
      knowledge: The use of hypofractionated VMAT is dosimetrically feasible for
      treating breast DCIS.

PMID- 29322830
TI  - Waiting for multidisciplinary chronic pain services: A prospective study over 2.5
      years.
AB  - Despite many patients waiting more than 2 years for treatment at publicly funded
      multidisciplinary chronic pain services, waitlist studies rarely examine beyond 6
      months. We investigated psychological adjustment and health-care utilisation of
      individuals ( N = 339) waiting <=30 months for appointments at an Australian
      tertiary pain unit. Outcomes were relatively stable during the first 6 months,
      but long-term deteriorations in pain-related interference, distress and pain
      acceptance were evident, albeit with sex differences. Sexes also differed in
      uptake of new treatments. Medication use increased over time, but pain severity
      and medication relief did not. Results suggest that early intervention is
      important, especially for women.

PMID- 29322831
TI  - Spiritual Health and Life-Orientation Measure: Psychometric properties of the
      Brazilian Portuguese version.
AB  - This study aimed to translate into Brazilian Portuguese and evaluate the main
      psychometric properties from Spiritual Health and Life-Orientation Measure in a
      sample of 487 students aged 9-15 years in Southern Brazil. Spiritual Health and
      Life-Orientation Measure is divided into Ideals and Lived Experience sections and
      showed high internal consistency reliability (Cronbach's alpha = 0.94).
      Comparison of mean values between age showed a tendency to decrease spirituality
      scores with increasing age. Discriminate validity of mean scores between groups
      of atheists, "spiritual, but not religious," and religious was significant in all
      domains (0.026 <  p < 0.001). Spiritual Health and Life-Orientation Measure
      presents adequate psychometric properties and may contribute to study
      spirituality in children and adolescents.

PMID- 29322832
TI  - Corrigendum.

PMID- 29322833
TI  - Genitourinary involvement of lymphomas on FDG-PET.
AB  - Primary extranodal lymphomatous involvement of the genitourinary tract is rare
      and secondary extranodal involvement in disseminated disease occurs more
      frequently. Imaging of metabolic activity with 2-(fluorine-18) fluoro-2-deoxy-d
      glucose (FDG) used in PET facilitates the identification of these extranodal
      sites of disease, particularly in the absence of structural lesions on
      conventional imaging modalities. Primary extranodal lymphoma affecting the
      genitourinary system is often caused by high-grade Non-Hodgkin's Lymphoma (NHL)
      with the most common subtype being diffuse large B-cell lymphoma (DLBCL).
      Although rare, the incidence of extranodal lymphoproliferative disease is
      increasing and a delay in diagnosis holds a poor prognosis. Familiarity with
      benign and physiological causes of FDG uptake, particularly due to the urinary
      tracer excretion is crucial in identifying sites of lymphomatous involvement in
      the genitourinary system. Additionally, non-lymphomatous malignancies are usually
      treated surgically, whereas lymphoma is primarily treated with chemotherapy
      and/or radiotherapy. Therefore, accurate identification and staging together with
      histological confirmation significantly impacts management of these patients.
      This article serves to review and illustrate the imaging findings on FDG-PET/CT
      of primary extranodal lymphoma affecting the genitourinary system.

PMID- 29322834
TI  - A tertiary centre experience of thoracic CT and cardiac MRI scanning in the
      presence of a reveal LINQ insertable cardiac monitoring system: a case series
      review of artefact, patient safety and data preservation.
AB  - OBJECTIVE: At our tertiary cardiothoracic centre, cardiac MRI and thoracic CT
      scans are performed in patients with implanted LINQ devices. The degree of
      foreign body artefact associated with the LINQ device, and its clinical
      importance, has not previously been assessed. A case series review was therefore
      performed with a simultaneous review of patient safety and data loss events,
      secondary to the MRI environment. METHODS: A local database search identified
      LINQ device patients who underwent thoracic CT or cardiac MRI scans between March
      2014 and December 2016. Images were reviewed by two radiologists, recording the
      presence of subcutaneous and intrathoracic artefact, and its clinical
      significance. Furthermore a specialist in cardiac rhythm management reviewed all
      LINQ data downloads undertaken before and after MRI scanning, and a search of the
      trust incident reporting system was performed. RESULTS: Minor subcutaneous
      artefact was present on all scans. Intrathoracic artefact was observed in 25.6%
      of thoracic CT scans and 33.3% of cardiac MRIs; however no clinically significant
      artefact was observed. Device downloads were only performed by 53.8% of patients
      prior to their MRI scan and 56.5% after their MRI scan. No adverse patient safety
      or data loss events were noted. CONCLUSION: The LINQ device does not produce
      clinically significant artefact, even when artefact extends into the
      intrathoracic space, which occurs in a third of MRIs and a quarter of CTs. MRI
      scanning of the LINQ device is safe with no evidence of inappropriate data loss.
      Advances in knowledge: This is the first published case series of CT and MRI
      scanning in LINQ patients and the first performed quantification of artefact
      related to the LINQ device.

PMID- 29322835
TI  - Toxic epidermal necrolysis versus cutaneous Graft-Versus-Host Disease in a
      hematopoietic stem cell transplant recipient: the role of elafin.

PMID- 29322836
TI  - Activation studies with amines and amino acids of the beta-carbonic anhydrase
      encoded by the Rv3273 gene from the pathogenic bacterium Mycobacterium
      tuberculosis.
AB  - The activation of a beta-class carbonic anhydrase (CAs, EC 4.2.1.1) from
      Mycobacterium tuberculosis, encoded by the gene Rv3273 (mtCA 3), was investigated
      using a panel of natural and non-natural amino acids and amines. mtCA 3 was
      effectively activated by D-DOPA, L-Trp, dopamine and serotonin, with KAs ranging
      between 8.98 and 12.1 uM. L-His and D-Tyr showed medium potency activating
      effects, with KAs in the range of 17.6-18.2 uM, whereas other amines and amino
      acids were relatively ineffective activators, with KAs in the range of 28.9-52.2
      uM. As the physiological roles of the three mtCAs present in this pathogen are
      currently poorly understood and considering that inhibition of these enzymes has
      strong antibacterial effects, discovering molecules that modulate their enzymatic
      activity may lead to a better understanding of the factors related to the
      invasion and colonisation of the host during Mycobacterium tuberculosis
      infection.

PMID- 29322838
TI  - Chronic myelomonocytic leukemia with central nervous system involvement.

PMID- 29322837
TI  - Association of advanced glycation end products, evaluated by skin
      autofluorescence, with lifestyle habits in a general Japanese population.
AB  - Objective Accumulation of advanced glycation end products (AGEs) occurs during
      normal aging but markedly accelerates in people with diabetes. AGEs may play a
      role in various age-related disorders. Several studies have demonstrated that
      skin autofluorescence (SAF) reflects accumulated tissue levels of AGEs. However,
      very few studies have investigated SAF in the general population. The purpose of
      the present study was to more thoroughly evaluate the potential association among
      SAF, chronological age, and lifestyle habits in the general population. Methods A
      large cross-sectional survey of 10,946 Japanese volunteers aged 20 to 79 years
      was conducted. Volunteers completed a self-administered questionnaire and
      underwent SAF measurement on their dominant forearms. The associations of SAF
      with age and lifestyle habits were analyzed using a multiple stepwise regression
      analysis. Results Age was independently correlated with SAF. Lifestyle habits
      such as physical activity, nonsmoking, adequate sleep, low mental stress level,
      eating breakfast, and abstaining from sugary food were each independently
      associated with lower SAF. Conclusions SAF was associated with age and healthy
      lifestyle habits in this general Japanese population. The present study suggests
      that SAF measurement is a convenient tool for evaluating habitual lifestyle
      behaviors and may have potential for preventative health education.

PMID- 29322839
TI  - Feasibility study of a human papillomavirus E6 and E7 oncoprotein test for the
      diagnosis of cervical precancer and cancer.
AB  - Objective To evaluate the clinical value of human papillomavirus (HPV) E6 and E7
      oncoprotein (HPV E6/E7) detection in the early screening of cervical cancer.
      Methods This prospective study evaluated all patients with suspected cervical
      intraepithelial neoplasia (CIN) as identified by the presence of at least one
      positive indicator from a ThinPrep cytologic test (TCT) and/or a Hybrid Capture 2
      (HC2) HPV DNA test. The levels of E6/E7 oncoproteins were determined using
      Western blot analysis. The diagnostic value of the HPV E6/E7 protein assay was
      compared with the clinical diagnosis from TCT, HC2 and the gold standard of
      cervical biopsy histology. Results A total of 450 patients were enrolled in the
      study and based on histological findings, 102 patients were diagnosed with CIN1
      (22.7%), 241 with CIN2 (53.6%), 96 with CIN3 (21.3%) and 11 with squamous cell
      carcinoma (2.4%). For a diagnosis of CIN2+, although the sensitivity of the HPV
      E6/E7 assay was lower than HC2 (65.5% versus 96.6%, respectively), the
      specificity was higher (38.2% versus 5.9%, respectively). The sensitivity of the
      HPV E6/E7 assay was higher than TCT (65.5% versus 36.2%, respectively).
      Conclusion Measuring HPV E6/E7 oncoprotein levels is a potential new biomarker
      for HPV type 16.

PMID- 29322841
TI  - The effect of lycopene on cytochrome P450 isoenzymes and P-glycoprotein by using
      human liver microsomes and Caco-2 cell monolayer model.
AB  - Lycopene is widely used as a dietary supplement. However, the effects of lycopene
      on cytochrome P450 (CYP) enzymes or P-glycoprotein (P-gp) are not comprehensive.
      The present study was performed to investigate the effects of lycopene on the CYP
      enzymes and P-gp activity. A cocktail method was used to evaluate the activities
      of CYP3A4, CYP2C9, CYP2C19, CYP2D6 and CYP2E1. Caco-2 cell monolayer model was
      carried out to assay lycopene on P-gp activity. The results indicated that
      lycopene had a moderate inhibitory effect on CYP2E1, with IC50 value of 43.65
      MUM, whereas no inhibitory effects on CYP3A4, CYP2C19, CYP2D6 and CYP2E1, with
      IC50 values all over 100 MUM. In addition, lycopene showed almost no inhibitory
      effect on rhodamine-123 efflux and uptake (p > .05), indicated no effects on P-gp
      activity. In conclusion, there should be required attention when lycopene are
      coadministered with other drugs that are metabolised by CYP2E1.

PMID- 29322840
TI  - Biochemical characterisation of a Kunitz-type inhibitor from Tamarindus indica L.
      seeds and its efficacy in reducing plasma leptin in an experimental model of
      obesity.
AB  - A trypsin inhibitor isolated from tamarind seed (TTI) has satietogenic effects in
      animals, increasing the cholecystokinin (CCK) in eutrophy and reducing leptin in
      obesity. We purified TTI (pTTI), characterised, and observed its effect upon CCK
      and leptin in obese Wistar rats. By HPLC, and after amplification of resolution,
      two protein fractions were observed: Fr1 and Fr2, with average mass of [M + 14H]+
      = 19,594,690 Da and [M + 13H]+ = 19,578,266 Da, respectively. The protein
      fractions showed 54 and 53 amino acid residues with the same sequence. pTTI
      presented resistance to temperature and pH variations; IC50 was 2.7 * 10-10 mol.L
      1 and Ki was 2.9 * 10-11 mol.L-1. The 2-DE revealed spots with isoelectric points
      between pH 5 and 6, and one near pH 8. pTTI action on leptin decrease was
      confirmed. We conclude that pTTI is a Kunitz trypsin inhibitor with possible
      biotechnological health-related application.

PMID- 29322842
TI  - CD133 expression and MYCN amplification induce chemoresistance and reduce average
      survival time in pediatric neuroblastoma.
AB  - Objectives Neuroblastoma (NB) is the most common pediatric solid tumor derived
      from the sympathetic nervous system. MYCN is amplified in nearly half of patients
      with NB, and its association with rapid disease progression and poor outcome is
      controversial. Characterization of cancer stem cells (CSCs) in NBs has been
      rarely studied. This study was performed to determine whether MYCN and CD133+
      CSCs are associated with chemotherapy resistance and the survival time of
      patients with NB. Methods Fifty patients with an unequivocal pathological
      diagnosis of NB were recruited. MYCN expression levels were measured before
      therapy. CSCs were derived and their multipotency tested by directed
      differentiation. The patients' responses to chemotherapy and average survival
      time were compared among the groups as follows: CD133+, CD133-, MYCN
      amplification >=5 times (i.e. MYCN>=5), MYCN<5, CD133+ plus MYCN>=5, and CD133-
      plus MYCN<5. Results CD133+ CSCs differentiated into neuron-like cells. CD133+
      patients had a significantly poorer response to chemotherapy than did CD133-
      patients. CD133+ plus MYCN>=5 patients had a significantly shorter average
      survival time than did CD133- plus MYCN<5 patients. Conclusions CD133+ CSCs are
      chemoresistance. CD133 expression and MYCN amplification can be used together as
      a prognostic indicator of disease outcome.

PMID- 29322843
TI  - Immunotherapy for brain tumors: understanding early successes and limitations.
AB  - INTRODUCTION: Adverse effects and toxicities related to standard treatments for
      brain tumors significantly reduce patients' quality of life. Although most
      immunotherapy approaches for solid tumors have not been successful, several early
      phase clinical trials are beginning to reveal a potential role for immunotherapy
      in the treatment of brain tumors. In particular, methods that activate the innate
      immune system and induce a polyclonal anti-cancer response have demonstrated that
      brain tumors are susceptible to immune-mediated tumor destruction. Compared with
      conventional therapies, modulation of the immune system may improve both
      survivorship and quality of life during and following treatment. Areas covered:
      An overview of mechanisms of immunotherapy in the context of current treatments
      for adult and pediatric brain tumors is provided. Results from recent clinical
      trials will be discussed, focusing on the favorable safety and efficacy profiles
      of immunotherapeutics. Expert commentary: Although it is too early to judge the
      long-term safety of immunotherapy for the treatment of patients with brain
      tumors, early results suggest that these drugs are well-tolerated and may improve
      survival and quality of life. Importantly, approaches that activate an anti-tumor
      immune response lay the framework for iterative development of immunotherapies
      that can reliably treat patients with brain tumors.

PMID- 29322844
TI  - Among middle-aged adults, snoring predicted hypertension independently of sleep
      apnoea.
AB  - Objective While the link between obstructive sleep apnoea (OSA) and hypertension
      is well established, the relationships between snoring, OSA, and hypertension
      remain unclear. This study aimed to evaluate the association between hypertension
      and snoring independently of OSA. Methods Adults with sleep difficulties
      underwent a one-night polysomnographic sleep assessment, including a thorough
      assessment of apnoea and snoring. Upon waking, blood pressure was measured, the
      measurement repeated after 15 min, in a resting position. Anthropometric data
      were recorded. Hypertension was defined as blood pressure >=140/90 mmHg or the
      use of antihypertensive medications. Results The study enrolled 181 adults (mean
      age 48.8 years; 119 males). Snoring, apnoea, blood pressure and anthropometric
      dimensions were highly associated. Patients with hypertension had higher levels
      of snoring and apnoea, as well as indicators of excess weight. Snoring was the
      most robust predictor of hypertension. Conclusions Snoring is a risk factor for
      hypertension independently of apnoea and anthropometric dimensions. While the
      presence of snoring is not able to replace a thorough polysomnographic evaluation
      of the apnoea-hypopnoea index and OSA, snoring as an acoustic signal is easily
      detectable. The early identification and management of snoring may reduce
      cardiovascular risk.

PMID- 29322846
TI  - PI3K/AKT/mTOR pathway in multiple myeloma: from basic biology to clinical
      promise.
AB  - Multiple myeloma (MM), a cancer of terminally differentiated plasma cells, is the
      second most common hematological malignancy. The disease is characterized by the
      accumulation of abnormal plasma cells in the bone marrow that remains in close
      association with other cells in the marrow microenvironment. In addition to the
      genomic alterations that commonly occur in MM, the interaction with cells in the
      marrow microenvironment promotes signaling events within the myeloma cells that
      enhances survival of MM cells. The phosphoinositide 3-kinase (PI3K)/protein
      kinase B (AKT)/mammalian target of rapamycin (mTOR) is such a pathway that is
      aberrantly activated in a large proportion of MM patients through numerous
      mechanisms and can play a role in resistance to several existing therapies making
      this a central pathway in MM pathophysiology. Here, we review the pathway, its
      role in MM, promising preclinical results obtained thus far and the clinical
      promise that drugs targeting this pathway have in MM.

PMID- 29322845
TI  - Medication disposal practices: Increasing patient and clinician education on safe
      methods.
AB  - Recent research suggests that the nation's water supply is contaminated with
      trace pharmaceuticals that exert a negative environmental and public health
      impact. Incorrect medication disposal methods (e.g. flushing medications down the
      toilet or drain) are a significant factor contributing to the presence of
      medication compounds in the aquatic environment. In this commentary, we provide a
      summary of the existing data on pharmaceuticals in the nation's water as well as
      the role of improper medication disposal methods on water contamination. We
      discuss statistics on improper medication disposal practices among patients and
      clinicians as well as recent advances in proper medication disposal methods as a
      solution to this problem. Currently, many patients and clinicians are not aware
      of proper medication disposal practices. We summarize the importance of patient
      and clinician education in advancing environmental-safe medication disposal
      methods.

PMID- 29322847
TI  - Tissue expanders with a focus on extremity reconstruction.
AB  - INTRODUCTION: Acute traumatic or surgical wounds that cannot be primarily closed
      often cause substantial morbidity and mortality. This often leads to increased
      costs from higher material expenses, more involved nursing care, and longer
      hospital stays. Advancements in soft tissue expansion has made it a popular
      alternative to facilitate early closure without the need for more complicated
      plastic surgical procedures. Areas covered: In this review, we briefly elaborate
      on the history and biomechanics of tissue expansion and provide comprehensive
      descriptions of traditional internal tissue expanders and a variety of
      contemporary external tissue expanders. We describe their uses, advantages,
      disadvantages, and clinical outcomes. The majority of articles reviewed include
      case series with level IV evidence. Outcome data was collected for studies after
      1990 using PubMed database. Expert commentary: An overall reduction in cost, time
      to-wound closure, hospital length-of-stay, and infection rate may be expected
      with most tissue expanders. However, further studies comparing outcomes and cost
      effectiveness of various expanders may be beneficial. Surgeons should be aware of
      the wide array of tissue expanders that are commercially available to
      individualize treatment based on thorough understanding of their advantages and
      disadvantages to optimize outcomes. We predict the use of external expanders to
      increase in the future and the need for more invasive procedures such as flaps to
      decrease.

PMID- 29322848
TI  - Inpatient satisfaction at different public sector hospitals of a metropolitan
      city in Pakistan: a comparative cross-sectional study.
AB  - OBJECTIVE: To observe inpatient satisfaction at different public sector hospitals
      of Karachi, Pakistan. METHODS: A cross sectional study was carried out during
      2010-2012 in four major public sector hospitals of Karachi. A total of 710
      patients completed the study. Responses were gathered in a self-structured
      questionnaire that comprised of four dimensions of satisfaction with doctor,
      staff, administration and treatment. Average Score of each dimension was taken
      and compared using one way analysis of variance. RESULT: Satisfaction with
      doctors, staff and administration of provincial and federal hospitals were
      comparatively similar (P > 0.05). However, satisfaction with treatment
      significantly differed in all four hospitals (P < 0.0001). Highest satisfaction
      with treatment was observed among inpatients of hospital running by medical
      institute (P < 0.0001). Comparison with respect to different departments revealed
      significant difference for treatment satisfaction of medicine and surgery units.
      Patients who were admitted from emergency mode acquired lowest satisfaction in
      all aspects. CONCLUSION: Response of inpatients from public sector hospitals
      showed satisfaction with healthcare personnel and related administration.
      However, treatment dimension needs to be improved to get more satisfaction.

PMID- 29322849
TI  - Safety profile of lenalidomide in patients with lower-risk myelodysplastic
      syndromes without del(5q): results of a phase 3 trial.
AB  - : The safety profile of lenalidomide use in lower-risk myelodysplastic syndromes
      (MDS) patients with del(5q) is well-established, but less is known in non-del(5q)
      patients. We provide safety data from a randomized, phase 3 trial evaluating
      lenalidomide in 239 patients with lower-risk non-del(5q) MDS
      ineligible/refractory to erythropoiesis-stimulating agents (ESAs). Compared with
      placebo, lenalidomide was associated with a higher incidence of grade 3-4
      treatment-emergent adverse events (TEAEs; 86% vs. 44%), but not risk of infection
      (p = .817) or hemorrhagic events (p = 1.000). Grade 3-4 non-hematologic TEAEs
      were rare (the incidence of grade 3-4 pneumonia, e.g. was 5.6% in the
      lenalidomide group and 2.5% in the placebo group). Common grade 1-2 non
      hematologic TEAEs did not require dose modifications or treatment
      discontinuation. Acute myeloid leukemia and second primary malignancies incidence
      was similar across treatment groups. Lenalidomide had a predictable and
      manageable safety profile in lower-risk non-del(5q) MDS patients
      ineligible/refractory to ESAs. Guidance on managing lenalidomide-related TEAEs is
      provided to help maintain patients on therapy to achieve maximum clinical
      benefit. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01029262.

PMID- 29322850
TI  - Clinical significance of intrapancreatic choledochal cyst excision in surgical
      management of type I choledochal cyst.
AB  - Objective To investigate the effectiveness of intrapancreatic choledochal cyst
      excision in treating type I choledochal cyst, and increase understanding of the
      need for thorough surgical management of the disease. Methods Primary and
      secondary (including multiple) surgical cases, treated between 2005 and 2015,
      were retrospectively analysed, and follow-up data of post-treatment effectiveness
      to date were reviewed. Differences in curative effects were compared between
      whole and partial excision of the choledochal cyst. Results Out of 350 cases,
      patients with whole excision of the choledochal cyst ( n = 272) experienced no
      associated symptoms in the long-term (3/272 [1.1%] experienced stomach ache or
      fever). Patients with partial resection of the choledochal cyst ( n = 78)
      developed associated symptoms, including new cyst, calculus of the bile duct
      (51/78 [65.4%]), and carcinogenesis (11/78 [14.1%]) in the residual
      intrapancreatic biliary duct. Post-treatment clinical manifestations were
      significantly different between patients with partial resection versus whole
      excision of the choledochal cyst ( P<0.05). Conclusion Surgical re-excision
      should be considered in patients with a residual intrapancreatic portion of the
      choledochal cyst due to prior incomplete surgery, regardless of clinical
      symptoms.

PMID- 29322851
TI  - Clinical and virological implications of A1846T and C1913A/G mutations of
      hepatitis B virus genome in severe liver diseases.
AB  - OBJECTIVE: Mutations occurring within different genes of hepatitis B virus (HBV)
      genome may have different clinical implications. This study aimed to observe the
      clinical and virological implications of the A1846T and C1913A/G mutations of HBV
      genome in the development and treatment outcome of severe liver diseases, which
      has not been previously determined. MATERIALS AND METHODS: A total of 438 cases
      of patients with liver diseases were retrospectively reviewed, including 146 with
      mild chronic hepatitis B infection (CHB-M), 146 with severe chronic hepatitis B
      infection (CHB-S), and 146 with acute-on-chronic liver failure (ACLF). Partial or
      full-length HBV genome was directly sequenced. Replicons containing A1846T,
      C1913A or other mutant sequences, or the wild-type counterparts were constructed
      respectively, and then transfected into HepG2 cells for phenotype analysis.
      RESULTS: There was significant difference in the detection rates of A1846T
      (30.82%, 40.41% and 55.48%, respectively) and C1913A/G (15.52%, 28.77%, and
      35.62%, respectively) among patients with CHB-M, those with CHB-S, and those with
      ACLF (p < .01). A1846T was significantly associated with the mortality of ACLF
      patients within six months after the disease onset (OR 1.704, p = .041). In vitro
      experiment revealed that A1846T mutant resulted in 3.20-fold and 1.85-fold
      increase of replication capacity and promoter activity, respectively compared
      with wild type counterpart (p < .001), while C1913A led to a significant decrease
      of core protein expression (p < .05). CONCLUSION: Occurrence of A1846T and C1913A
      is positively associated with clinical presentations of severe liver disease.
      A1846T mutation is significantly associated with poor prognosis of ACLF.

PMID- 29322852
TI  - Anion inhibition studies of a beta carbonic anhydrase from the malaria mosquito
      Anopheles gambiae.
AB  - An anion inhibition study of the beta-class carbonic anhydrase, AgaCA, from the
      malaria mosquito Anopheles gambiae is reported. A series of simple as well as
      complex inorganic anions, and small molecules known to interact with CAs were
      included in the study. Bromide, iodide, bisulphite, perchlorate, perrhenate,
      perruthenate, and peroxydisulphate were ineffective AgaCA inhibitors, with KIs >
      200 mM. Fluoride, chloride, cyanate, thiocyanate, cyanide, bicarbonate,
      carbonate, nitrite, nitrate, sulphate, stannate, selenate, tellurate,
      diphosphate, divanadate, tetraborate, selenocyanide, and trithiocarbonate showed
      KIs in the range of 1.80-9.46 mM, whereas N,N-diethyldithiocarbamate was a
      submillimolar AgaCA inhibitor (KI of 0.65 mM). The most effective AgaCA
      inhibitors were sulphamide, sulphamic acid, phenylboronic acid and phenylarsonic
      acid, with inhibition constants in the range of 21-84 uM. The control of insect
      vectors responsible of the transmission of many protozoan diseases is rather
      difficult nowadays, and finding agents which can interfere with these processes,
      as the enzyme inhibitors investigated here, may arrest the spread of these
      diseases worldwide.

PMID- 29322853
TI  - Laser ablation of the biliary tree: in vivo proof of concept as potential
      treatment of unresectable cholangiocarcinoma.
AB  - OBJECTIVES: The palliative treatment of cholangiocarcinoma is based on stent
      placement with well-known procedure-related complications. Consequently,
      alternative energy-based techniques were put forward with controversial long-term
      results. This study aims to evaluate the safety and effectiveness of biliary tree
      laser ablation (LA) in terms of: (i) absence of perforation, (ii) temperature
      increase, (iii) induced thermal damage in in vivo models. MATERIALS AND METHODS:
      The common bile duct and cystic ducts of two pigs were ablated with a diode laser
      (circumferential irradiation pattern) for 6 and 3 min at 7 W. Laser settings were
      chosen from previous ex vivo experiments. Local temperature was monitored through
      a fibre Bragg grating (FBG) sensor embedded into the laser delivery probe.
      Histopathological analysis of the ablated specimen was performed through in situ
      endomicroscopy, haematoxylin and eosin (H&E) and nicotinamide adenine
      dinucleotide (NADH) stains. RESULTS: Temperature reached a plateau of 53  degrees
      C with consequent thermal damage on the application area, regardless of laser
      settings and application sites. No perforation was detected macroscopically or
      microscopically. At the H&E stain, wall integrity was always preserved. The NADH
      stain allowed to evaluate damage extension. It turned out that the ablation
      spreading width depended on application time and duct diameter. In situ
      endomicroscopy revealed a clear distinction between ablated and non-ablated
      areas. CONCLUSIONS: The temperature distribution obtained through LA proved to
      induce a safe and effective intraductal coagulative necrosis of biliary ducts.
      These results represent the basis for further experiments on tumour-bearing
      models for the treatment of obstructive cholangiocarcinoma.

PMID- 29322855
TI  - Fatigue in pediatric patients with familial Mediterranean fever.
AB  - OBJECTIVES: Familial Mediterranean fever (FMF) is characterized by recurrent,
      self-limited attacks of fever with serositis involving the peritoneum, pleura and
      joints. Fatigue is a common problem in many pediatric rheumatic diseases;
      however, has not been evaluated systematically in FMF patients. Accordingly, the
      aim of this study was to evaluate fatigue and its possible allied factors in
      patients with FMF. METHODS: Patients with FMF, aged between 10 and 21 years, were
      assessed by completed validated fatigue questionnaire (Checklist Individual
      Strength-20). As a control group, patients with chronic rheumatic diseases and
      healthy children without any chronic disease were included. RESULTS: The study
      group comprised 111 patients with FMF, 54 with other chronic rheumatic diseases
      and 79 healthy subjects. While the CIS-20 total score and subscale scores
      (including subjective experience of fatigue) were similar between patients with
      FMF and those with other chronic rheumatic diseases (p > .05); both groups had
      significantly higher scores when compared with healthy subjects (p < .05). FMF
      patients with musculoskeletal complaints had significantly higher scores of
      subjective experiences of fatigue when compared to those without those
      complaints. CONCLUSIONS: Fatigue is a common but unrecognized complaint in
      patients with FMF. Familial Mediterranean fever seems to be a chronic disease
      with inter attack ongoing complaints.

PMID- 29322854
TI  - Are platelet volume indices related to mortality in hospitalized children on
      mechanical ventilation?
AB  - Objectives To investigate platelet volume indices and in-hospital mortality in
      children on mechanical ventilation. Methods This retrospective study included
      children aged <16 years on mechanical ventilation, and compared parameters,
      measured on admission, between survivors and non-survivors. Dynamic platelet
      volume indices over the first 7 days were visualized. Independent risk factors of
      mortality were identified using multivariate logistic regression analysis.
      Results Out of 2 319 children aged 28 days-3 years, serum albumin (odds ratio
      [OR] 0.9, 95% confidence interval [CI] 0.85, 0.96), bilirubin (OR 1.01, 95% CI
      1.0, 1.77), and lactic acid (OR 1.22, 95% CI 1.05, 1.38) levels were associated
      with mortality. Out of 2 415 children aged > 3 years, procalcitonin (OR 1.01, 95%
      CI 1.0, 1.01) and lactic acid (OR 1.22, 95% CI 1.09, 1.35) were associated with
      mortality. Platelet volume indices on admission were not independently associated
      with mortality in either group. Mean platelet volume (MPV) and platelet
      distribution width (PDW) showed different trends in non-survivors versus
      survivors over 1 week in both age groups. Conclusions Platelet volume indices may
      be associated with mortality in critically ill children receiving mechanical
      ventilation.

PMID- 29322856
TI  - Perforation risk and intra-uterine devices: results of the EURAS-IUD 5-year
      extension study.
AB  - OBJECTIVES: The objective of this analysis was to identify intra-uterine devices
      (IUD) perforations detected from 12 to 60 months following IUD insertion, and to
      combine this information with (our previously published) data about perforations
      detected in the first 12 months to calculate cumulative perforation rates.
      METHODS AND MATERIALS: Prospective, non-interventional cohort study with new
      users of levonorgestrel-releasing intra-uterine systems (LNG-IUS) and copper-IUD.
      The original cohort included 61,448 women followed for 12 months. Of these, we
      had sufficient resources to perform an additional follow-up and analysis at 60
      months in 39,009 women. Inclusion criteria for this analysis was insertion prior
      to 31 July 2010. All potential cases were validated via the health care
      professional or medical records. Crude and adjusted relative risks were
      calculated using a logistic regression model. RESULTS: We identified 23
      additional perforations (19 LNG-IUS and 4 copper-IUD) more than 12 months after
      insertion. Added to perforations detected at 12 months, the overall perforation
      rate was 2.1 per 1000 insertions (95% CI: 1.6-2.8) for LNG-IUS users (40 + 19
      perforations/27,630 insertions) and 1.6 per 1000 insertions (95% CI: 0.9-2.5) for
      copper-IUD users (14 + 4 perforations/11,379 insertions). LNG-IUS users had a
      borderline higher risk of perforation compared with copper-IUD users (ORadj 1.7;
      95% CI: 1.0-2.8). Forty-five (58%) of the 77 perforations were associated with
      suspected risk factors. Breastfeeding (RR 4.9, 95% CI: 3.0-7.8) and time since
      delivery (RR 3.0, CI: 1.5-5.4) remained significant risk factors in perforations
      detected after 12 months. No perforations resulted in serious injury to intra
      abdominal or pelvic structures. CONCLUSIONS: The incidence of uterine
      perforations in this study was low, although higher than the commonly reported
      rate. Approximately one third of perforations are detected 12 months after
      insertion. Clinical sequalae of perforations are generally mild and associated
      with a very low risk of injury to intra-abdominal and pelvic structures.
      Implications Uterine perforation is a rare risk associated with intra-uterine
      device use. Late diagnosed perforations can occur, although women can be
      reassured that the morbidity associated with detection and removal is low.

PMID- 29322857
TI  - Morphometric analysis for evaluating the relation between incisal guidance angle,
      occlusal plane angle, and functional temporomandibular joint shape variation.
AB  - OBJECTIVE: The correlations between morphology of the temporomandibular joint
      structure, the anterior guidance angle, and occlusal plane were investigated.
      MATERIALS AND METHODS: A cone beam computed tomography analysis was performed in
      158 patients (86 women and 72 men). 3D software was employed to obtain the
      coordinates of the shape of the incisal guidance angle, occlusal guidance angle,
      articular fossa, and mandibular condyle. Generalized Procrustes analysis
      including principal components analysis (PCA) were performed and produced
      principal components (PCs) scores of each shape and their centroid size (CS).
      RESULTS: A significant Pearson correlation coefficient of 0.3451 (p < .001) was
      observed between the incisal guidance angle and occlusal plane. The CS also
      showed a correlation with the incisal guidance angle, but not with the occlusal
      plane angle. The PCA results revealed that there were no significant correlations
      between the temporomandibular joint structure (TMJ) shape (fossa and condyle) and
      the incisal guidance angle. CONCLUSIONS: Incisor guidance angle and occlusal
      plane angle were correlated. In addition, there was a correlation between CS and
      incisal guidance angle. In the PCA, It can be concluded that the size is more
      related to the incisor guidance angle than the morphological factors of the
      constituent components of the TMJ.

PMID- 29322858
TI  - Epidemiology of mental health conditions in incoming division I collegiate
      athletes.
AB  - OBJECTIVES: The purpose of this study is to examine the epidemiology of mental
      health conditions in incoming American Division I collegiate athletes. METHODS:
      Pre-participation physical questionnaires from 1118 incoming student athletes at
      a Division I Institution were collected retrospectively from 2011-2017. Data
      collected included lifetime history of any mental health condition,
      musculoskeletal injuries, concussions, and post-concussion depression. History of
      any mental health condition was evaluated by gender and sport played. It was also
      evaluated in comparison to musculoskeletal injuries and concussions. RESULTS: The
      lifetime prevalence of any mental health condition was 14.0% for all athletes,
      14.2% for male athletes, and 13.6% for female athletes. Individual sports
      reported a greater prevalence (17.2%) than did team sports (11.8%) (p = 0.010).
      The prevalence was also higher in contact sports (16.4%) than in non-contact
      sports (12.5%), although this difference was not statistically significant (p =
      0.072). There was a significant association between mental health condition and
      all four major groups of injuries examined: upper extremity (p = 0.043), lower
      extremity (p = 0.007), axial skeletal (p < 0.001), and concussions (p = 0.039).
      Post-concussion depression occurred in 2.0% of all athletes reporting a
      concussion. CONCLUSION: The lifetime prevalence of mental health conditions in
      this population (14.0%) is far less than estimates in the general population.
      This observation may be due to a combination of factors including
      exercise/athletic participation mitigating depressive symptoms, competitive
      selection, and underreporting. History of a mental health condition may be
      associated with injury, although causation cannot be determined.

PMID- 29322859
TI  - Electrostatic hazards of charging of bedclothes and ignition in medical
      facilities.
AB  - We investigated the charge generated on bedclothes (cotton and polyester) during
      bedding exchange with different humidities and the ignitability of an alcohol
      based hand sanitizer (72.3 mass% ethanol) due to static spark with different
      temperatures to identify the hazards of electrostatic shocks and ignitions
      occurring previously in medical facilities. The results indicated that charging
      of the polyester bedclothes may induce a human body potential of over about 10
      kV, resulting in shocks even at a relative humidity of 50%, and a human body
      potential of higher than about 8 kV can cause a risk for the ignition of the hand
      sanitizer. The grounding of human bodies via footwear and flooring, therefore, is
      essential to avoid such hazards (or to reduce such risks).

PMID- 29322861
TI  - Community mobility after stroke: a systematic review.
AB  - : Background Stroke is the leading cause of severe disability and many survivors
      report long-term physical or cognitive impairments that may impact their ability
      to achieve community mobility (CM). PURPOSE: To determine the extent to which
      people with chronic stroke achieve CM compared to age-matched norms or non
      neurologically impaired controls. Methods The StrokEDGE outcome measures were
      searched to identify validated tools that included >25% of items addressing CM.
      MEDLINE, CINAHL, Google Scholar, PubMed, PEDro and the Cochrane databases were
      searched from 2001 to 2015 with the identified outcome measures cross-referenced
      against search terms related to stroke and CM. INCLUSION CRITERIA: utilized a
      validated CM outcome measure, chronic (>3 months post) stroke survivors, and
      randomized controlled trial, observational or cohort study design. One reviewer
      screened the studies and performed data extraction and three performed quality
      appraisal. Fourteen studies met all inclusion criteria. Results Stroke survivors
      have impaired CM as demonstrated by 30-83% of normative or non-stroke subject CM
      scores. As time post-stroke increased, CM improved only slightly. Factors found
      to correlate with the CM were age, education, general well-being, emotional
      state, motor function and coordination, independence in activities of daily
      living, balance, endurance and driving status. Limitations of this review include
      a relatively high functioning cohort, no meta-analysis and reliance on outcome
      measures not specifically designed to measure CM. Conclusion Survivors of stroke
      may experience a significant decrease in CM compared to people without
      neurological injury. Rehabilitation addressing motor function, coordination,
      independence in activities of daily living, balance and endurance may be
      important for achieving higher levels of CM. Outcome measures directly addressing
      CM are needed.

PMID- 29322862
TI  - Feasibility of developing a passive sampler for sampling heavy metals in BMPs for
      stormwater runoff management.
AB  - Structural Best Management Practices (BMPs) have been used for stormwater
      treatment and management for several decades. How to monitor these BMPs
      performance reliably and economically is a challenge. This paper reports the
      feasibility of developing a flow through passive sampler (PS) based on Amberlite
      IRC748 ion exchange resin operated in kinetic regime for sampling heavy metals in
      BMPs (infiltration systems) for stormwater treatment and management. Tests were
      conducted using batch reactors and laboratory-scale BMPs. Batch reactor results
      indicate that PSs performed desirably with consistent and rapid metal uptake, and
      thus, the resin-based PS is feasible to be used for stormwater sampling. In lab
      scale BMPs tests, the resin PSs were employed for sampling influent and effluent
      of BMPs loaded with synthetic stormwater for storm durations of 0.5, 3, and 12
      hours. The removal efficiency of heavy metals in the BMPs as predicted by PSs was
      very similar to the actual treatment efficiencies obtained from control BMPs,
      with errors ranging from -5% to 2%, indicating that the PSs can be used for
      sampling stormwater and monitoring BMPs. The next step for this sampler will be
      to develop a method for evaluating the volume of water passing the PS during the
      sampling period.

PMID- 29322860
TI  - Antenatal and Neonatal Antecedents of Executive Dysfunctions in Extremely Preterm
      Children.
AB  - To find out why children born extremely preterm are at heightened risk of
      executive dysfunctions, the authors assessed 716 children who were 10 years old
      born extremely preterm whose IQ was >= 70. A working memory dysfunction (n =
      169), an inhibition dysfunction (n = 360), a switching dysfunction (355), and all
      3 (executive dysfunction; n = 107) were defined on the basis of Z-scores <= -1 on
      the Differential Ability Scales-II Working Memory composite, and/or on the NEPSY
      II Inhibition-Inhibition and Inhibition-Switching subtests. All risk profiles
      include an indicator of socioeconomic disadvantage. The risk profile of each of
      the 3 individual dysfunctions includes an indicator of the newborn's immaturity,
      and the risk profiles of the inhibition dysfunction and switching dysfunction
      also include an indicator of inflammation. Only the switching dysfunction was
      associated with fetal growth restriction. The risk factors for executive
      dysfunction can be subsumed under the 4 themes of socioeconomic disadvantage,
      immaturity/vulnerability, inflammation, and fetal growth restriction.

PMID- 29322863
TI  - Transcultural factors related to depressive psychopathology in Sri Lankan
      migrants living in Australia.

PMID- 29322864
TI  - Effects of Danshen tablets on pharmacokinetics of atorvastatin calcium in rats
      and its potential mechanism.
AB  - CONTEXT: Danshen tablets (DST), an effective traditional Chinese multi-herbal
      formula, are often combined with atorvastatin calcium (AC) for treating coronary
      heart disease in the clinic. OBJECTIVE: This study investigated the effects of
      DST on the pharmacokinetics of AC and the potential mechanism. MATERIALS AND
      METHODS: The pharmacokinetics of AC (1 mg/kg) with or without pretreatment of DST
      (100 mg/kg) were investigated using LC-MS/MS. The effects of DST (50 MUg/mL) on
      the metabolic stability of AC were also investigated using rat liver microsome
      incubation systems. RESULTS: The results indicated that Cmax (23.87 +/- 4.27 vs.
      38.94 +/- 5.32 ng/mL), AUC(0-t) (41.01 +/- 11.32 vs. 77.28 +/- 12.92 ng h/mL),
      and t1/2 (1.91 +/- 0.18 vs. 2.74 +/- 0.23 h) decreased significantly (p < 0.05)
      when DST and AC were co-administered, which suggested that DST might influence
      the pharmacokinetic behavior of AC when they are co-administered. The metabolic
      stability (t1/2) of AC was also decreased (25.7 +/- 5.2 vs. 42.5 +/- 6.1) with
      the pretreatment of DST. DISCUSSION AND CONCLUSIONS: This study indicated that
      the main components in DST could accelerate the metabolism of AC in rat liver
      microsomes and change the pharmacokinetic behaviors of AC. So these results
      showed that the herb-drug interaction between DST and AC might occur when they
      were co-administered. Therefore, the clinical dose of AC should be adjusted when
      DST and AC are co-administered.

PMID- 29322865
TI  - A mathematical model of tumour growth with Beddington-DeAngelis functional
      response: a case of cancer without disease.
AB  - A previously published mathematical model, governing tumour growth with mixed
      immunotherapy and chemotherapy treatments, is modified and studied. The search
      time, which is assumed to be neglectable in the previously published model, is
      incorporated into the functional response for tumour-cell lysis by effector
      cells. The model exhibits bistability where a tumour-cell population threshold
      exists. A tumour with an initial cell population below the threshold can be
      controlled by the immune system and remains microscopic and asymptomatic called
      cancer without disease while that above the threshold grows to lethal size.
      Bifurcation analysis shows that (a) the chemotherapy-induced damage may cause a
      microscopic tumour, which would never grow to become lethal if untreated, to grow
      to lethal size, (b) applying chemotherapy alone requires a large dosage to be
      successful,

PMID- 29322866
TI  - How does language change after an intensive treatment on imitation?
AB  - The main aim of our study was to investigate the role of imitation in improving
      word-finding difficulties in a group of aphasic subjects. For this purpose, we
      designed software based on the computerised program described by Lee et al.
      (2010). Seven subjects with aphasia resulting from a brain injury were enrolled
      in the study. A battery of tests was administered to participants one month
      before the treatment (T0) and immediately before its beginning (T1) with the aim
      of detecting their language difficulties. In the period between T0 and T1
      sessions, participants underwent traditional logopaedic and neuropsychological
      rehabilitation. The treatment lasted 45 days with 90-minute sessions per day and
      it was personalised in terms of difficulty for each of the subjects. During every
      session the task required participants to carefully observe and then imitate six
      actors while pronouncing aloud a series of words and sentences describing a set
      of items. The results showed a significant improvement in the whole sample and in
      all the analysed measures only between T1 and T2 (post-training evaluation),
      while, as expected, no improvement was registered between T0 and T1. Such
      outcomes are consistent with research showing the key role played by imitation in
      the word retrieval process following aphasia.

PMID- 29322868
TI  - In silico approaches to evaluate the molecular properties of organophosphate
      compounds to inhibit acetylcholinesterase activity in housefly.
AB  - Organophosphate compounds (OPC) have become the primary choice as insecticides
      and are widely used across the world. Additionally, OPCs were also commonly used
      as a chemical warfare agent that triggers a great challenge to public safety.
      Exposure of OPCs to human causes immediate excitation of cholinergic
      neurotransmission through transient elevation of synaptic acetylcholine (ACh)
      levels and accumulations. Likewise, prolonged exposure of OPCs can affect the
      processes in immune response, carbohydrate metabolism, cardiovascular toxicity,
      and several others. Studies revealed that the toxicity of OPCs was provoked by
      inhibition of acetylcholinesterase (AChE). Therefore, combined in silico
      approaches - pharmacophore-based 3D-QSAR model; docking and Molecular Dynamics
      (MD) - were used to assess the precise and comprehensive effects of series of
      known OP-derived compounds together with its -log LD50 values. The selected five
      featured pharmacophore model - AAHHR.61 - displayed the highest correlation (R2 =
      .9166), cross-validated coefficient (Q2 = .8221), F = 63.2, Pearson-R = .9615
      with low RMSE = .2621 values obtained using five component PLS factors.
      Subsequently, the well-validated model was then used as a 3D query to search
      novel OPCs using a high-throughput virtual screening technique. Simultaneously,
      the docking studies predicted the binding pose of the most active OPC in the
      MdAChE binding pocket. Additionally, the stability of docking was verified using
      MD simulation. The results revealed that OP22 and predicted lead compounds bound
      tightly to S315 of MdAChE through potential hydrogen bond interaction over time.
      Overall, this study might provide valuable insight into binding mode of OPCs and
      hit compounds to inhibit AChE in housefly.

PMID- 29322867
TI  - Implementing voluntary medical male circumcision using an innovative, integrated,
      health systems approach: experiences from 21 districts in Zimbabwe.
AB  - BACKGROUND: Despite increased support for voluntary medical male circumcision
      (VMMC) to reduce HIV incidence, current VMMC progress falls short. Slow progress
      in VMMC expansion may be partially attributed to emphasis on vertical (stand
      alone) over more integrated implementation models that are more responsive to
      local needs. In 2013, the ZAZIC consortium began implementation of a 5-year,
      integrated VMMC program jointly with Ministry of Health and Child Care (MoHCC) in
      Zimbabwe. OBJECTIVE: To explore ZAZIC's approach emphasizing existing healthcare
      workers and infrastructure, increasing program sustainability and resilience.
      METHODS: A process evaluation utilizing routine quantitative data. Interviews
      with key MoHCC informants illuminate program strengths and weaknesses. METHODS: A
      process evaluation utilizing routine quantitative data. Interviews with key MoHCC
      informants illuminate program strengths and weaknesses. RESULTS: In start-up and
      year 1 (March 2013-September, 2014), ZAZIC expanded from two to 36 static VMMC
      sites and conducted 46,011 VMMCs; 39,840 completed from October 2013 to September
      2014. From October 2014 to September 2015, 44,868 VMMCs demonstrated 13%
      increased productivity. In October, 2015, ZAZIC was required by its donor to
      consolidate service provision from 21 to 10 districts over a 3-month period.
      Despite this shock, 57,282 VMMCs were completed from October 2015 to September
      2016 followed by 44,414 VMMCs in only 6 months, from October 2016 to March 2017.
      Overall, ZAZIC performed 192,575 VMMCs from March 2013 to March, 2017. The vast
      majority of VMMCs were completed safely by MoHCC staff with a reported moderate
      and severe adverse event rate of 0.3%. CONCLUSION: The safety, flexibility, and
      pace of scale-up associated with the integrated VMMC model appears similar to
      vertical delivery with potential benefits of capacity building, sustainability
      and health system strengthening. These models also appear more adaptable to local
      contexts. Although more complicated than traditional approaches to program
      implementation, attention should be given to this country-led approach for its
      potential to spur positive health system changes, including building local
      ownership, capacity, and infrastructure for future public health programming.

PMID- 29322869
TI  - Identifying, organizing and prioritizing ideas on how to enhance ADL ability.
AB  - BACKGROUND: There is a need to develop evidence-based occupational therapy
      programs aiming at enhancing the ability to perform Activities of Daily Living
      (ADL) among persons living with chronic conditions. Information from different
      sources is to be integrated in the development process. Thus, it is necessary to
      engage both occupational therapists and persons living with chronic conditions in
      suggesting ideas on how to enhance the ADL ability. OBJECTIVE: To identify,
      organize and prioritize ideas on how to enhance ability to perform ADL in persons
      with chronic conditions. MATERIAL AND METHOD: Group Concept Mapping, involving
      brainstorming, sorting, labeling, rating and validation of ideas, was applied
      among persons with chronic conditions (n = <= 18) and occupational therapists (n
      = <= 23). Multidimensional scaling analysis and cluster analyzes were applied.
      RESULTS: 149 ideas were identified and organized into seven clusters related to
      applying new adaptational strategies, personal factors, social surroundings and
      relevant services and opportunities. Each cluster contained ideas of high
      priority to persons with chronic conditions and/or occupational therapists.
      CONCLUSION: A span of highly relevant themes, illustrated the complexity of
      enhancing ADL ability. This should be considered in the development of
      interventions aiming at enhancing ADL ability in persons with chronic conditions.

PMID- 29322872
TI  - A Collaborative Approach to Improve Consistent Use of Procalcitonin in Lower
      Respiratory Tract Infections.
AB  - BACKGROUND: Procalcitonin (PCT) is a biomarker that can help differentiate
      bacterial from viral infections and has been extensively studied in patients with
      sepsis and pneumonia to guide antibiotic therapy. However, there is poor
      adherence to prescribed algorithms when used to discontinue antibiotics in the
      real world. A quality improvement project was implemented to increase consistent
      use of PCT. OBJECTIVE: To evaluate use of PCT and impact on antibiotic length of
      therapy (LOT) preimplementation and postimplementation of a quality improvement
      initiative. METHODS: This was a single-center retrospective cohort study in
      patients with lower respiratory tract infections (LRTIs). RESULTS: In all, 330
      patients were included in this study. Following implementation of the quality
      improvement initiative, ordering PCT in the first 24 hours increased from 59.6%
      to 75.5% ( P = 0.011). Documentation to discontinue antibiotics in patients with
      low initial PCT values increased from 13.2% to 28.6% ( P = 0.100). Increased PCT
      use correlated with an overall mean reduction of 1.05 antibiotic days between
      cohorts (6.82 +/- 3.88 vs 5.77 +/- 3.43, P = 0.028). There was no difference in
      incidence of antibiotic-associated adverse effects or 30-day hospital readmission
      rates attributed to pneumonia. CONCLUSIONS: Consistent use of PCT was achieved
      through a collaborative effort with the clinical pharmacy and hospitalist staff.
      Increased use of PCT was associated with a significant reduction in antibiotic
      LOT among patients with LRTIs. When controlling for other factors, low initial
      PCT values had the strongest influence on discontinuing antibiotics within 72
      hours in the intervention group.

PMID- 29322871
TI  - Are Extremely Low Gestational Age Newborns Born to Obese Women at Increased Risk
      of Cerebral Palsy at 2 Years?
AB  - The authors hypothesized that the risk of cerebral palsy at 2 years in children
      born extremely preterm to overweight and obese women is increased relative to the
      risk among children born to neither overweight nor obese women. In a multicenter
      prospective cohort study, the authors created multinomial logistic regression
      models of the risk of diparetic, quadriparetic, and hemiparetic cerebral palsy
      that included the prepregnancy body mass index of mothers of 1014 children born
      extremely preterm, cerebral palsy diagnoses of children at 2 years, as well as
      information about potential confounders. Overweight and obese women were not at
      increased risk of giving birth to a child who had cerebral palsy. The risk ratios
      associated with overweight varied between 1.1 for quadriparesis (95% CI = 0.5,
      2.1) to 2.0 for hemiparesis (95% CI = 0.4, 9.8). The risk ratios associated with
      obesity varied between 0.7 for diparesis (95% CI = 0.2, 2.5) to 2.5 for
      hemiparesis (95% CI = 0.4, 13).

PMID- 29322873
TI  - Trends and Complications in Open Versus Endoscopic Carpal Tunnel Release in
      Private Payer and Medicare Patient Populations.
AB  - PURPOSE: The purpose of this study was to report trends, complications, and costs
      associated with endoscopic carpal tunnel release (ECTR) and open carpal tunnel
      release (OCTR). METHODS: Using Current Procedural Terminology (CPT) and
      International Classification of Diseases, Ninth Revision (ICD-9) codes, patients
      who had open versus endoscopic carpal tunnel release (CTR) were identified
      retrospectively in the PearlDiver database from both the Medicare and Humana (a
      private payer health insurance) populations from 2005 to 2014. These groups were
      then evaluated for postoperative complications, including wound infection within
      90 days, wound dehiscence within 90 days, and intraoperative median nerve injury.
      We also used the data output for each group to compare the cost of the 2
      procedure types. Data were analyzed via the Student t test. Statistical
      significance was set at P < .05. RESULTS: A significantly lower percentage of
      patients in the endoscopic CTR group had a postoperative infection (5.21 vs 7.97
      per 1000 patients per year, P < .001; 7.36 vs 11.23 per 1000 patients per year, P
      < .001) and wound dehiscence (1.58 vs 2.87 per 1000 patients per year, P < .001;
      2.14 vs 3.73 per 1000 patients per year, P < .05) than open CTR group in the
      Medicare and Humana populations, respectively. Median nerve injury occurred
      0.59/1000 ECTRs versus 1.69/1000 OCTRs (Medicare) and 1.96/1000 ECTRs versus
      3.72/1000 OCTRs (Humana). Endoscopic CTR cost was more than open CTR for both the
      Medicare population ($1643 vs $1015 per procedure, P < .001) and Humana
      population ($1928 vs $1191 per procedure, P < .001). CONCLUSIONS: In both the
      Medicare and private insurance patient populations, endoscopic CTR is associated
      with fewer postoperative complications than open CTR, but is associated with
      greater expenses.

PMID- 29322874
TI  - MRSA Incidence and Antibiotic Trends in Urban Hand Infections: A 10-Year
      Longitudinal Study.
AB  - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is the most
      reported pathogen in hand infections at urban medical centers throughout the
      country. Antibiotic sensitivity trends are not well known. The purposes of this
      study were to examine and determine the drug resistance trends for MRSA
      infections of the hand and to provide recommendations for empiric antibiotic
      treatment based on sensitivity profiles. METHODS: A 10-year longitudinal,
      retrospective chart review was performed on all culture-positive hand infections
      encountered at a single urban medical center from 2005 to 2014. The proportions
      of all organisms were calculated for each year and collectively. MRSA infections
      were additionally subanalyzed for antibiotic sensitivity. RESULTS: A total of 815
      culture-positive hand infections were identified. Overall, MRSA grew on culture
      in 46% of cases. A trend toward decreasing annual MRSA incidence was noted over
      the 10-year study period. There was a steady increase in polymicrobial infections
      during the same time. Resistance to clindamycin increased steadily during the 10
      year study, starting at 4% in 2008 but growing to 31% by 2014. Similarly,
      levofloxacin resistance consistently increased throughout the study, reaching its
      peak at 56% in 2014. CONCLUSIONS: The annual incidence of MRSA in hand infections
      has declined overall but remains the most common pathogen. There has been an
      alternative increase in the number of polymicrobial infections. MRSA resistance
      to clindamycin and levofloxacin consistently increased during the study period.
      Empiric antibiotic therapy for hand infections should not only avoid penicillin
      and other beta-lactams but should also consider avoiding clindamycin and
      levofloxacin for empiric treatment.

PMID- 29322875
TI  - Biomechanical Analysis of Capsular Repair Versus Arthrex TFCC Ulnar Tunnel Repair
      for Triangular Fibrocartilage Complex Tears.
AB  - BACKGROUND: This study compares the effectiveness of a peripheral capsular repair
      with a knotless arthroscopic transosseous ulnar tunnel repair (TR) in restoring
      distal radioulnar joint (DRUJ) stability and stiffness in the setting of a
      massive triangular fibrocartilage complex (TFCC) tear. METHODS: Eight matched
      pairs of fresh-frozen cadaveric forearms were tested. Each forearm was tested in
      supination and pronation using 3-dimensional (3D) optical tracking devices prior
      to any intervention. Each specimen then underwent a diagnostic wrist arthroscopy
      and sectioning of the TFCC's deep and superficial fibers. All specimens were then
      retested to assess instability secondary to the tear. The TFCC was repaired with
      either a peripheral capsular repair (CR) using three 2-0 polydioxanone sutures or
      a transosseous ulnar TR using a 2-0 FiberWire, and then retested (statistical
      significance; P < .05). RESULTS: After TFCC arthroscopic sectioning, all
      specimens were unstable with a significant increase in translation and a
      significant decrease in stiffness. TFCC repair with TR resulted in displacement
      and stiffness similar to the native tissue. CR specimens were found to have
      significantly greater displacement and significantly decreased stiffness compared
      with the intact state. CONCLUSIONS: Arthroscopic sectioning of the TFCC resulted
      in DRUJ instability, as measured by stiffness and ulnar translation. TR
      effectively restored DRUJ stability and demonstrated no significant difference in
      postoperative stiffness or maximal displacement when compared with the intact
      specimen in pronation and supination. This study provides biomechanical evidence
      that an arthroscopic ulnar tunnel technique can restore stability to the DRUJ
      after a massive TFCC tear.

PMID- 29322876
TI  - Study of Telomere Length in Preimplanted Cultured Chondrocytes.
AB  - Design In the process of cell division, the extremes of the eukaryotic
      chromosomes are progressively shortening, and this phenomenon is related to cell
      degeneration and senescence. The treatment of cartilage lesions with autologous
      chondrocytes implies that cells proliferate in an artificial environment. We have
      studied the viability of cultured chondrocytes after measurement of their
      telomere length before implantation. Methods Articular cartilage biopsies (B1,
      B2, and B3) were obtained from 3 patients (2 males and 1 female) with knee
      cartilage defects, who were going to be treated with chondrocyte implantation.
      Chondrocytes were cultured in DMEM with autologous serum. After the third
      passage, an aliquot of 1 million cells was removed to estimate the telomere
      length and the remaining cells were implanted. Telomere length was measured by
      quantitative fluorescent in situ hybridization (Q-FISH). Patients' clinical
      outcome was determined preoperatively, and 12 and 24 months postimplantation with
      the International Knee Documentation Committee (IKDC) questionnaire. Results
      After chondrocyte implantation, IKDC score doubled at 12 and 24 months with
      regard to the basal value. After 3 passages, chondrocytes were cultured for a
      mean of 45.67 days, the mean duplication time being 4.53 days and the mean number
      of cell divisions being 10.04 during the culture period. The 20th percentile of
      telomere lengths were 6.84, 6.96, and 7.06 kbp and the median telomere lengths
      10.30, 10.47, and 10.73 kbp, respectively. No significant correlation was found
      between IKDC score and telomere length. Conclusion Culturing autologous
      chondrocytes for implantation is not related to cell senescence in terms of
      telomere length.

PMID- 29322877
TI  - Topographical Variation of Human Femoral Articular Cartilage Thickness, T1rho and
      T2 Relaxation Times Is Related to Local Loading during Walking.
AB  - Objective Early detection of degenerative changes in the cartilage matrix
      composition is essential for evaluating early interventions that slow down
      osteoarthritis (OA) initiation. T1rho and T2 relaxation times were found to be
      effective for detecting early changes in proteoglycan and collagen content. To
      use these magnetic resonance imaging (MRI) methods, it is important to document
      the topographical variation in cartilage thickness, T1rho and T2 relaxation times
      in a healthy population. As OA is partially mechanically driven, the relation
      between these MRI-based parameters and localized mechanical loading during
      walking was investigated. Design MR images were acquired in 14 healthy adults and
      cartilage thickness and T1rho and T2 relaxation times were determined.
      Experimental gait data was collected and processed using musculoskeletal modeling
      to identify weight-bearing zones and estimate the contact force impulse during
      gait. Variation of the cartilage properties (i.e., thickness, T1rho, and T2) over
      the femoral cartilage was analyzed and compared between the weight-bearing and
      non-weight-bearing zone of the medial and lateral condyle as well as the
      trochlea. Results Medial condyle cartilage thickness was correlated to the
      contact force impulse ( r = 0.78). Lower T1rho, indicating increased proteoglycan
      content, was found in the medial weight-bearing zone. T2 was higher in all weight
      bearing zones compared with the non-weight-bearing zones, indicating lower
      relative collagen content. Conclusions The current results suggest that medial
      condyle cartilage is adapted as a long-term protective response to localized
      loading during a frequently performed task and that the weight-bearing zone of
      the medial condyle has superior weight bearing capacities compared with the non
      weight-bearing zones.

PMID- 29322878
TI  - Mechanical, Cellular, and Proteomic Properties of Laryngotracheal Cartilage.
AB  - The larynx sometimes requires repair and reconstruction due to cancer resection,
      trauma, stenosis, or developmental disruptions. Bioengineering has provided some
      scaffolding materials and initial attempts at tissue engineering, especially of
      the trachea, have been made. The critical issues of providing protection,
      maintaining a patent airway, and controlling swallowing and phonation, require
      that the regenerated laryngotracheal cartilages must have mechanical and material
      properties that closely mimic native tissue. These properties are determined by
      the cellular and proteomic characteristics of these tissues. However, little is
      known of these properties for these specific cartilages. This review considers
      what is known and what issues need to be addressed.

PMID- 29322879
TI  - Puerarin prevents diabetic cardiomyopathy in vivo and in vitro by inhibition of
      inflammation.
AB  - Diabetic cardiomyopathy (DCM) is one of the chief diabetes mellitus
      complications. Inflammation factors may be one reason for the damage from DM. The
      purpose of this research is to study the potential protective effects of puerarin
      on DM and the possible mechanisms of action related to NF-kappaB signal pathway.
      Following administration of puerarin to the disease model rat, several changes
      were observed including the changes of serum biochemical index, improved
      diastolic dysfunction, and enhanced endogenous antioxidant enzymes activities,
      further NF-kappaB signaling activation. Puerarin showed cardio-protective effects
      on DCM by inhibiting inflammation, and it might be a potential candidate for the
      treatment of DCM.

PMID- 29322880
TI  - Reversible splenial lesion syndrome due to oxcarbazepine withdrawal: case report
      and literature review.
AB  - Background Reversible splenial lesion syndrome is a distinct entity
      radiologically characterized by a reversible lesion in the splenium of the corpus
      callosum. According to previous reports, this condition may be associated with
      antiepileptic drug use or withdrawal. We herein report a case of reversible
      splenial lesion syndrome associated with oxcarbazepine withdrawal. Case Report A
      39-year-old man presented with an 8-year history of epileptic seizures. During
      the previous 3 years, he had taken oxcarbazepine irregularly. One week prior to
      admission, he withdrew the oxcarbazepine on his own, and the epilepsy became
      aggravated. Magnetic resonance imaging (MRI) revealed an isolated lesion in the
      splenium of the corpus callosum with slight hypointensity on T1-weighted imaging
      and slight hyperintensity on T2-weighted imaging. Regular oxcarbazepine was
      prescribed. Over a 5-month follow-up period, repeat MRI showed that the abnormal
      signals in the splenium of the corpus callosum had completely disappeared.
      Conclusion Reversible splenial lesion syndrome is a rare clinicoradiological
      disorder that can resolve spontaneously with a favorable outcome. Clinicians
      should be aware of this condition and that oxcarbazepine withdrawal is a possible
      etiological factor.

PMID- 29322881
TI  - Radiofrequency ablation of primary thyroid carcinoma: efficacy according to the
      types of thyroid carcinoma.
AB  - OBJECTIVE: To evaluate the efficacy of ultrasound (US)-guided radiofrequency
      ablation (RFA) according to the types of thyroid carcinoma, particularly in
      patients with a high-surgical risk. MATERIALS AND METHODS: Eight patients with
      nine tumours of pathologically proven papillary and anaplastic carcinoma were
      treated by US-guided RFA. Patients with primary thyroid carcinoma were divided
      into three groups; group (1) Anaplastic carcinoma, group (2) papillary
      macrocarcinoma, and group (3) papillary microcarcinoma. We evaluated changes in
      clinical symptoms, tumour volume and local tumour recurrence/metastasis after
      RFA. Patients were followed up at 1, 6 and 12 months and annually thereafter.
      RESULTS: Among nine tumours, one anaplastic carcinoma was treated three times and
      the other anaplastic carcinoma and one papillary macrocarcinoma were treated
      twice. Group 3 were treated once. The initial mean tumour volume was 107.9 +/-
      78.6 (with neck bulging), 126.9 (with neck bulging) and 0.16 +/- 0.08 mL (without
      cosmetic or symptomatic problems) in groups 1-3, respectively. Group 1 showed no
      improvement in clinical symptoms or neck bulging after RFA, whereas group 2
      demonstrated a decreased tumour volume measuring 0.7 mL with improved neck
      bulging. In group 3, mean volume decreased measuring 0.07 +/- 0.12 mL. No local
      tumour recurrence or metastatic lesion was detected during the mean follow-up of
      19.3 months in papillary carcinomas. No major complications were encountered.
      CONCLUSIONS: In patients with primary thyroid carcinoma, RFA achieved excellent
      local tumour control for papillary macro- and microcarcinoma; however, its
      clinical effect on anaplastic carcinoma was questionable.

PMID- 29322882
TI  - Molecular detection and characterization of transient bovine viral diarrhea virus
      (BVDV) infections in cattle commingled with ten BVDV persistently infected
      cattle.
AB  - Fifty-three cattle of unknown serologic status that were not persistently
      infected (PI) with bovine viral diarrhea virus (BVDV) were commingled with 10
      cattle that were PI with different strains of BVDV, and were monitored for an
      extended commingle period using a reverse-transcription real-time PCR (RT-rtPCR)
      BVDV assay on various sample types. Transient infections with BVDV were also
      assessed by virus isolation, virus neutralization (VN) assays, and direct buffy
      coat 5'-UTR sequencing. Infections were demonstrated in all cattle by RT-rtPCR;
      however, the detection rate was dependent on the type of sample. Buffy coat
      samples demonstrated a significantly greater number of positive results ( p <=
      0.05) than either serum or nasal swab samples. Presence of elevated BVDV VN
      titers at the onset inversely correlated with the number of test days positive
      that an individual would be identified by RT-rtPCR from buffy coat samples, and
      directly correlated with the average Ct values accumulated over all RT-rtPCR test
      days from buffy coat samples. Both single and mixed genotype/subgenotype/strain
      infections were detected in individual cattle by direct sample 5'-UTR sequencing.
      A BVDV-2a strain from a PI animal was found to be the predominant strain
      infecting 64% of all non-PI cattle; BVDV-1b strains originating from 3 PI cattle
      were never detected in non-PI cattle. Although direct sample 5'-UTR sequencing
      was capable of demonstrating mixed BVDV infections, identifying all strains
      suspected was not always efficient or possible.

PMID- 29322883
TI  - Cardiac mesothelial papillary hyperplasia in four dogs.
AB  - Mesothelial papillary hyperplasia (MPH) has been described as an incidental
      finding on the epicardial surface of clinically normal laboratory Beagle dogs. We
      describe MPH in 4 dogs diagnosed with acute cardiac tamponade (1 case) or chronic
      cardiac disease (3 cases). Cardiac MPH appeared as distinct, soft, irregular
      villous plaques on the epicardial surface of the auricles and occasionally the
      ventricles. Histologically, areas of MPH were composed of multiple papillary
      fronds arising from the epicardial surface and projecting into the pericardial
      space. Fronds were covered by cuboidal and occasionally vacuolated mesothelial
      cells and were supported by loose fibrovascular stroma with various degrees of
      edema and inflammation. Although these may represent incidental findings with no
      clinical significance, the gross appearance warrants differentiation from other
      conditions. Additional insight into the pathogenesis of MPH is needed to fully
      understand its significance in the face of concurrent cardiac disease.

PMID- 29322884
TI  - High mortality in foals associated with Salmonella enterica subsp. enterica
      Abortusequi infection in Italy.
AB  - Salmonella enterica subsp. enterica serovar Abortusequi is frequently reported as
      a cause of abortion in mares and neonatal septicemia and polyarthritis in Asian
      and African countries, but only sporadically in Europe and the United States. We
      report an outbreak of S. Abortusequi in foals in Italy, characterized by high
      mortality. In a herd of Murgese horses, 10 of 34 newborns died at birth and a
      further 7 died, after developing severe clinical signs, during the first 10 d of
      life. Tissue specimens from different organs of 2 dead foals, synovial fluids
      from 4 sick foals, and vaginal and rectal swabs from their dams were cultured. A
      total of 16 isolates, all as pure cultures, were obtained and identified as
      Salmonella. The isolates exhibited the same antimicrobial resistance pattern and
      the same sequence type, ST251, a type that has been associated with S.
      Abortusequi. Six of 16 isolates were serotyped and found to be S. Abortusequi
      4,12:-:e,n,x. Equine practitioners should be aware of S. Abortusequi infection as
      a cause of neonatal mortality in foals.

PMID- 29322885
TI  - Analysis of a 15-years' experience in including shoulder muscles, when treating
      upper-limb spasticity post-stroke with botulinum toxin type A.
AB  - Background Botulinum toxin type-A (BoNTA) is a recognized treatment for upper
      limb spasticity (ULS) after stroke, but there aren't many studies analyzing its
      effect in shoulder muscles. Objective To evaluate the efficacy of BoNTA
      injections for ULS, when shoulder muscles are included. Methods A cross-sectional
      study. Data from clinical forms of outpatients, treated at a Rehabilitation
      Center (2001-2016). Analyzes: goals of treatment; demographic
      characteristics/goal; treatment success, using Goal Attainment Scaling. Results
      Eighty-six stroke-patients, submitted to 547 BoNTA treatment sessions. The most
      injected shoulder muscles were subscapularis (SC) 35%, pectoralis major (PM) 31%,
      deltoideus 14%. The most selected goals for treatment were: involuntary movements
      (IM) 33%, pain/discomfort (PD) 26%, and mobility (MOB) 18%. Patients achieved or
      overachieved the IM goal in 76%, PD in 78%, and MOB in 79%. Patients with IM goal
      were younger (p < 0.01), than those setting other goal types; PD patients, were
      older (p < 0.019), treated half a year earlier (p < 0.01), and had more
      spasticity (MAS ? 0.15); MOB patients were younger (p = 0.04) and less spastic
      (MAS ? 0.12). Achieving PD goal impacted positively in improving MOB (p = 0.042)
      and passive function (p = 0.018). Conclusion When treating ULS, including
      shoulder muscles, the most frequent goals were IM, PD e MOB. The most injected
      muscles were SC and PM. The treatment was successful in a large percentage of
      cases. Achieving the PD goal was associated with greater success at other goals
      of treatment. BoNTA demonstrated a positive effect in controlling symptoms and
      improving function.

PMID- 29322887
TI  - Functional outcome after proximal humerus fracture fixation : understanding the
      risk factors.
AB  - The purpose is to identify risk factors of functional outcome following proximal
      humerus open reduction and internal fixation. Patients treated for proximal
      humerus fractures with open reduction and internal fixation were enrolled in a
      prospective data registry. Patients were evaluated for function using the
      Disability of the Arm, Shoulder and Hand score for 12 months and as available
      beyond 12 months. Univariate analyses were conducted to identify variables
      associated with functional outcome. Significant variables were included in a
      multivariate regression predicting functional outcome. Demographics and minimum
      of 12 month follow-up were available for 129 patients (75%). Multiple regression
      demonstrated postoperative complication (B=8.515 p=0.045), education level (B=
      6.269p<0.0005), age (B=0.241p=0.049) and Charlson Comorbidity Index (B=6.578,
      p=0.001) were all significant predictors of functional outcome. Orthopaedic
      surgeons can use education level, comorbidities, age, and postoperative
      complication information to screen patients for worse outcomes, establish
      expectations, and guide care.

PMID- 29322886
TI  - Chronicity, crisis, and the 'end of AIDS'.
AB  - In biomedical, public health, and popular discourses, the 'end of AIDS' has
      emerged as a predominant way to understand the future of HIV research and
      prevention. This approach is predicated on structuring and responding to HIV in
      ways that underscore its presumed lifelong nature. In this article, I examine the
      phenomenon of HIV chronicity that undergirds the 'end of AIDS' discourse. In
      particular, I explore how the logic of HIV chronicity, induced by technological
      advances in treatment and global financial and political investments, intensifies
      long-term uncertainty and prolonged crisis. Focusing on over 10 years of
      anthropological and public health research in the United States, I argue that HIV
      chronicity, and subsequently, the 'end of AIDS' discourse, obscure the on-going
      HIV crisis in particular global communities, especially among marginalised and
      ageing populations who live in under-resourced areas. By tracing the 'end of
      AIDS' discourse in my field sites and in other global locations, I describe how
      HIV chronicity signals a continuing global crisis and persistent social precarity
      rather than a 'break' with a hopeless past or a promising future free from AIDS.

PMID- 29322888
TI  - Epidemiology of scapular fractures.
AB  - The aim of the study has been to acquire basic epidemiological data based on a
      representative group of patients with scapular fractures treated in one centre.
      The study analyses group of 250 patients. Diagnostics was based on CT
      examinations, in 227 cases with 3D reconstructions, in 97 cases compared with
      operative findings. Fractures were classified according to the modified
      anatomical classification of Tscherne and Christ. The analysed groups of patients
      include only the fracture lines whose existence has been verified by 3D CT
      reconstructions and intraoperative findings. The most common fracture in the
      group was that of the scapular body (52%), followed by fractures of the glenoid
      fossa (29%), fractures of the processes (11%) and fractures of the scapular neck
      (8%). The most frequent associated injuries to the ipsilateral shoulder girdle
      were clavicular fractures (19%). Scapular fractures occur primarily in men,
      predominantly in 4th - 6th decades (66 % patients). The group of women was
      significantly older as compared to men (p = 0.017). The group of patients with
      scapular neck fractures was significantly younger as compared to the age of
      patients with glenoid fracture (p = 0.021) and scapular body fracture (p =
      0.035).

PMID- 29322889
TI  - Outcomes of open reduction and internal fixation in displaced intra-articular
      scapular fractures : a case series.
AB  - Scapular fractures are rare injuries and usually occur due to high energy trauma.
      Displaced Intra articular fractures usually require operative treatment and
      yields better outcomes as compared to conservative management. To assess the
      functional and radiological outcomes of displaced intra-articular scapular
      fractures managed with open reduction and internal fixation. 12 patients were
      retrospectively reviewed and included in the study. Post-operative functional
      outcomes were assessed using mean quick DASH (Disability of arm, hand and
      shoulder) score while radiological outcomes were analyzed as percentage of
      implant cut-through, mal-union, non-union or infection.  The mean follow up was
      14 months. Mean age was 40 years. The mean quick DASH score was 7.19 +/- 4.86.
      All of the patients had successful clinical and radiological healing and pain
      free movements. Open reduction and internal fixation in displaced intra-articular
      scapular-fractures yields excellent and promising outcomes.

PMID- 29322890
TI  - An analysis of the course of carpal tunnel syndrome before operation.
AB  - : This work reports the results of an analysis into the course of carpal tunnel
      syndrome before operation in 479 patients, predominantly women, aged a mean of 58
      years, who were scheduled for carpal tunnel operation. The patients were asked to
      characterise in detail the course of the disease and what determined the decision
      to undergo surgery. RESULTS: We identified two specific patterns of CTS course:
      progressive and preservative/mild. Patients with short-lasting disease suffer
      first of all from symptoms, but the longer the duration, the more pronounced the
      functional impairment. In a proportion of patients with longer-lasting disease,
      spontaneous resolution may occur, for up to a year or more. Bilateral involvement
      is more common than unilateral and the interval between involvement of the other
      hand is a mean of 10 months. For most patients the primary motivation to undergo
      surgery is troublesome symptoms (pain and paraesthesia). Functional impairment is
      of secondary importance, however, its prominence increases in older patients and
      in those with longer-lasting disease.

PMID- 29322891
TI  - Eaton and Littler Ligament Reconstruction for the Painful first Carpometacarpal
      Joint : Patient satisfaction.
AB  - The ligamentous reconstruction according to Eaton and Littler (7) was designed to
      restore the stability of the carpometacarpal joint of the thumb. We evaluated the
      patients' satisfaction after an Eaton and Littler-procedure as well as possible
      risk factors in the development of thumb basal joint instability. A retrospective
      chart review and clinical assessment or telephone survey are executed in 33
      patients, with a mean follow-up of 7 years. Only 45% of the patients were
      satisfied. Within the group of clinical assessed patients, there were significant
      differences in thumb function comparing operated with not operated side. Overall
      joint hypermobility can be a contributing factor for this thumb basal joint
      instability, but has no effect on the outcome after an Eaton-Littler procedure.

PMID- 29322892
TI  - Could the orthopaedic surgeon deployed in austere setting perform flaps on the
      leg?
AB  - The orthopaedic military surgeons deployed in operations are led to perform soft
      tissue coverage on the lower limb. The purpose of this study was to evaluate if
      flaps performed by surgeons' non-specialist in reconstructive surgery are
      associated with good outcome. All patients operated for a flap on the leg in
      French Forward Surgical Team deployed in theatre of operations between 2003 and
      2013 were retrospectively reviewed. Forty-nine patients were included, for a
      total of 54 flaps' procedures. Indications were open fractures in 25 cases and
      osseous infections in 29 cases. No flap was performed on French soldiers. All the
      flaps were pedicle. Outcome was favourable for more than 90% of flaps with no
      statistical difference between muscular and fasciocutaneous flap and with regard
      to the indication. In conclusion, an orthopaedic surgeon deployed in austere
      setting with significant good outcome can perform reconstructive surgery with
      legs' flaps.

PMID- 29322893
TI  - Long term self esteem assessment after height increase by lengthening and then
      nailing.
AB  - The purpose of the study is to assess the long term psychosocial functioning
      after height increase, using the external fixation then nailing method. Rosenberg
      Self-esteem scale and a questionnaire to assess social functioning were completed
      by 28 patients both preoperatively and at a mean follow-up of 7 years. The mean
      total score of RSE self-esteem for the 28 patients before lengthening was 21.5
      (SD 1.03) (20-24). The mean total score of RSE for the patients 1 year after
      lengthening was 22 (SD 1.17) (20-24) with highly significant difference (p =
      0.002).The mean total RSE self-esteem score after 7 years was 21.7 (SD 1.12) (21
      25) with no significant difference (p = 0.11) Improvement was an evident in the
      short term self esteem after 1 year of follow up of the patients with height
      increase. On the other hand, there was an evident deterioration in the long term
      psychosocial evaluation during follow up after 7 years of height increase,
      returning to near pre-operative levels of self esteem.

PMID- 29322894
TI  - Patient restrictions following total hip arthroplasty: A national survey.
AB  - In this prospective nation-wide web based survey we describe the current practice
      regarding patient restrictions following total hip arthroplasty. A web-based
      survey involving 20 items was developed and tested prior to administration. The
      questionnaire included general information, type of restrictions, specification
      and duration of restrictions. The target population consisted of all orthopaedic
      surgeons registered with the Dutch Orthopaedic Association working at one of the
      94 orthopaedic departments in the Netherlands. The response rate of the
      orthopaedic departments was 78% (n=74). The majority of orthopaedic departments
      use patient restrictions following THA. Restrictions were used with different
      rates per type of surgical approach: anterior (69%), anterolateral (100%),
      straight lateral (94%) and posterolateral (93%). The duration of these
      restrictions is generally six weeks. Patient restrictions following THA are
      current practice, regardless of the surgical approach.

PMID- 29322895
TI  - Union rates and midterm results after Extended Trochanteric Osteotomy in Revision
      Hip Arthroplasty. Useful and safe technique.
AB  - Aim of this study was to evaluate the outcome fol-lowing extended trochanteric
      osteotomy in series of single surgeon, with emphasis on complications and union
      of osteotomy. Retrospective Case Series of all patients who had revision total
      hip replacement surgery performed by senior author between 2003 and 2012, with
      follow up between 1 and 10 years. 108 cases of revision hip arthroplasty with use
      of Extended Trochanteric Osteotomy were evaluated. In 101 cases solid bony union
      was achieved. In 7 cases where the bony union was not established, an
      asymptomatic and stable position was achieved. In 12 cases greater trochanter
      fracture was noted postoperatively with proximal migration 5 to 15mm. 1 patient
      required surgery to re-attach greater trochanter. Extended Trochanteric Osteotomy
      is a safe and very useful technique that can be used in revision hip surgery.

PMID- 29322896
TI  - Influence of varus/valgus positioning of the Nanos(r) and Metha(r) short-stemmed
      prostheses on stress shielding of metaphyseal bone.
AB  - The aim of this study was to analyze bone remodeling around the Nanos(r) (Smith &
      Nephew) and Metha(r) (Aesculap AG) implants as a function of varus/valgus stem
      positioning. In 75 patients with diagnosed coxarthrosis, either Nanos(r) (n= 51)
      or Metha(r) (n= 24) prostheses were implanted. Digital assessment of plain
      radiographs immediately, 97 days, and 381 days after THA showed no clinically
      relevant migration, angulation, or change in offset and center of rotation. The
      DEXA scans showed significant BMD changes in Gruen zones 1 (-12.8%), 2 (-3.3%), 6
      (+6.4%), and 7(-7.8%)(t-test). The pre/postoperative CCD for the Nanos(r) was 129
      degrees / 135 degrees  and for the Metha(r) 131 degrees / 127 degrees . Linear
      regression analysis showed no prediction for BMD by postoperative CCD or stem
      type. In conclusion, there was no clinically-relevant influence on proximal femur
      BMD according to varus/valgus implantation of the Nanos(r) or Metha(r)
      prostheses.

PMID- 29322897
TI  - Survival of the Birmingham hip resurfacing in young men up to 13 years post
      operatively.
AB  - The aim of this study was to determine the medium to long term survivorship of
      the Birmingham Hip Resurfacing prosthesis in an independent series of young men.
      The medical records and radiographs of all men aged 55 and under who had
      undergone Birmingham hip resurfacing by the senior author were reviewed. Patients
      who had not attended recent follow-up or had been previously discharged were
      contacted by telephone. Between 1999 and 2011 a total of 147 hips were resurfaced
      in 155 patients (mean age 47 years (19 to 55)) with minimum 5 year follow-up
      (mean 8.2, range 5 to 13.9 years). Eleven hips were revised giving overall
      cumulative survival of 88.8% at 13 years. In conclusion, this independent, single
      surgeon series demonstrates acceptable survival of the Birmingham Hip resurfacing
      in young men. It remains a valid option in certain cases but we believe
      alternative bearings are more suitable for most patients.

PMID- 29322898
TI  - The complications after open hip dislocation in hip surgery.
AB  - Our purpose is to evaluate the complications of open hip dislocation, which is
      used as a helpful technique in hip surgery. We have retrospectively reviewed 45
      hips of 44 cases who applied open hip dislocation with various indications in our
      institute between the years 2006-2013. There were 27 males and 17 females whose
      mean age was 31,9 (range, 11-58) years with mean follow-up time of 56,9 months
      (range, 13-106). The number of cases with at least one complication related to
      open hip dislocation was 27. Within our series 14 hips have developed only 1
      complication, 1 hip have 2, 10 hips have 3 and 2 hips have 4 different
      complications. Regarding Dindo-Clavien classification 17 hips were evaluated as
      Grade I (38%), 3 hips were Grade IIa (7%), 2 hips were Grade IIb (4%) and 5 hips
      were Grade III (11%). In conclusion, the absence of major complications after
      open hip dislocation does not make it absolutely safe. Open hip dislocations can
      only be indicated when trochanteric complications are considered. The patients
      need to be well informed on potential issues and risks.

PMID- 29322899
TI  - Is the pelvis stable during supine total hip arthroplasty?
AB  - Intra- operative changes in pelvic position during total hip arthroplasty (THA)
      can affect acetabular orientation. We evaluated these changes during supine THA
      using a proprietary mobile application called PelvicTracker. Twenty- two patients
      undergoing THA using direct anterior approach were included in the study. In the
      sagittal plane, the pelvis was extended (anterior tilt) as compared to the start
      of surgery in 19/ 22 hips at the time of cup implantation (mean extension: 3.1
      degrees ; range: 1 degrees -6 degrees ). In the transverse plane, the pelvis was
      rolled to the opposite side of surgery in 12 hips (mean roll: 2.8 degrees ;
      range: 1 degrees -5 degrees ), to the same side in 8 hips (mean roll: 3.9 degrees
      , range: 1 degrees -9 degrees ) and unchanged in 2 hips at the time of cup
      implantation. Predicted change in cup version of >=5 degrees  due to changes in
      pelvic position was seen in 7/22 (32%) patients. Although minor, changes in
      pelvic position do occur during supine THA which may affect acetabular
      orientation.

PMID- 29322900
TI  - Surgical technique description : Transosseous 'over the top' reconstruction of
      capsule and tendons in primary total hip arthroplasty using a posterior approach.
AB  - Dislocation after total hip arthroplasty (THA) remains a devastating complication
      and a primary cause for revision arthroplasty. Historical data indicate that a
      posterior approach is associated with a higher dislocation rate. In this study,
      we present a highly reliable and anatomical reconstruction, based on the
      biomechanical findings of a previous cadaveric experiment. The posterior soft
      tissues were repaired in 2 layers. First a reattachment of the posterior
      orbicular ligament is performed at the anterior capsule. Subsequently a
      transosseous 'over the top' reinsertion of both capsule and tendons is performed
      close to there anatomical insertion. We prospectively collected data of 408 THAs
      from January 2004 until December 2013, through a posterior approach and with a
      capsule and tendon reconstruction based on a previous cadaveric study. There was
      a low early dislocation rate in primary THA (one of 408 THAs, 0,2%) and no
      complications related to the technique. This anatomical reconstruction of both
      capsule and tendons is associated with a low dislocation rate without
      complications at the level of the greater trochanter.

PMID- 29322901
TI  - Primary total hip arthroplasty after acetabular fracture using intra-acetabular
      bended plates.

PMID- 29322902
TI  - Comparison between the Harris- and Oxford Hip Score to evaluate outcomes one-year
      after total hip arthroplasty.
AB  - Harris Hip Score (HHS) is a surgeon administered measurement for assessing hip
      function before and after total hip arthroplasties (THA). Patient reported
      outcome measurements (PROMs) such as the Oxford Hip Score (OHS) are increasingly
      used. HHS was compaired to the OHS assessing whether the HHS can be replaced by
      the OHS for clinical evaluation of THAs. All 155 patients (167 THAs) were asked
      to complete an OHS before and one-year after surgery. The surgeon independently
      scored the HHS at the same time points. We examined and compared the clinimetric
      properties of both instruments. Internal consistency reliability of the OHS was
      notably higher than that of the HHS at all occasions. HHS had a higher effect
      size (4.1) than the OHS (2.1). Ceiling effect at follow up was 55.6% (HHS) and
      36.4% (OHS). Spearman's rank correlation between HHS and OHS was 0.57 at baseline
      and 0.65 and after one year. The correlation between the change scores was 0.50.
      The Oxford Hip Score is of good use in quality assessment after THA.

PMID- 29322903
TI  - Difficult to treat osteoarticulars infections : Focus on Mycobacterial and Fungal
      infection.
AB  - Bone and joint infections are rare but often devastating. While bacteria are most
      commonly encountered organisms, mycobacteria and fungi are less frequent.
      Management of the latter is often more complex, especially in the presence of
      foreign material. We will increasingly be faced with mycobacterial and fungal
      bone infections, as medical conditions and newer therapeutics lead to more
      immunosuppression. In this article, we will review osteomyelitis, septic
      arthritis and peri-prosthetic joint infections related to mycobacteria and fungi.

PMID- 29322904
TI  - Modular bicompartmental knee arthroplasty : Indications, technique, prosthetic
      design, and results.
AB  - The shifting demographics of patients with localized knee arthritis, including
      younger, more active patients, is a chief motivation for mounting interest in
      tissue preserving surgical substitutes for total knee arthroplasty (TKA).
      Unlinked, modular bi-compartmental knee arthroplasty (MBKA) is an emerging knee
      resurfacing approach that provides a conservative alternative to TKA. Arthritis
      involving both patellofemoral and either medial or lateral tibiofemoral
      compartments, with no significant deformity or bone deficiency, preserved motion,
      and intact cruciate ligaments, can be effectively managed with MBKA. It is
      tailored to treat the pathologic areas of knees with bicompartmental arthritis
      with the benefit of improved function and tissue conservation. MBKA done in
      appropriate patients, using precise technique, with appropriate implants has
      shown to give good short and long term functional results. Long term results
      using modern MBKA implants are awaited and may further establish the durability
      and success of the procedure.

PMID- 29322905
TI  - Pre-discharge postoperative radiographs after primary total knee replacement :
      tradition or science?
AB  - Consistent evidence exists on the inutility of immediate postoperative
      radiographs after a total knee replacement (TKR). We hypothesized that
      eliminating the pre-discharge film would not have any effect on the postoperative
      patient outcomes. Retrospective analysis of prospectively collected data was
      performed on 220 knees. Patients undergoing a simple primary TKR operated by 2
      surgeons (Surgeon A and B) from January 2013 to July 2015 were divided into 2
      groups (Groups 1 and 2 having 112 and 108 knees respectively). While Surgeon A
      routinely asked for the second postoperative day pre-discharge radiograph,
      Surgeon B directly performed weight bearing radiographs 6 weeks postoperatively.
      Greater knee pain was seen in Group 1 (p = 0.01). No changes in rehabilitation
      protocols based on pre-discharge radiographs, complications, medico-legal issues
      or revision surgery could be identified in any patient. The quality of the pre
      discharge radiographs was adequate in 65 of the 112 knees (58%). A cost reduction
      of approximately $220 per patient was observed with the exclusion of the pre
      discharge film. Eliminating routine inpatient pre-discharge radio-graphs after
      simple primary TKR does not alter the rehabilitation protocol, identify any of
      the standard complication or have any medico-legal implications. On the contrary,
      these films seem to increase postoperative pain and costs.

PMID- 29322906
TI  - Distal femoral medial closing wedge osteotomy for degenerative valgus knee : mid
      term results in active patients.
AB  - Distal femoral medial closing wedge osteotomy (DFMCWO) may be a valuable
      treatment for arthritic valgus knees in young and active adults, with the
      possible aim of procrastinating knee replacement. 32 valgus knees (mean age :
      41.4+/-11.2) treated with DFMCWO were retrospectively reviewed. All the knees had
      a lateral compartment osteoarthritis graded I-II-III according to Kellgren
      Lawrence classification. 20 knees had osteochondral lesions, treated with
      microfractures (8) or bone marrow derived cells transplantation (12). Patients
      were clinically (IKDC, KOOS, NRS, Tegner) and radiologically evaluated. A mean
      follow-up of 62.12+/-15.65 was achieved. KOOS score peaked at 24 months, showed a
      decremental trend, achieved a final results of 79,59+/-17,14. Similar trend was
      evident for IKDC. The final NRS score was 2.73+/-1.82 ; the final Tegner score
      was 4.81+/-1.56. Radiographs showed degenerative progression in 5 knees : 2
      patients underwent knee replacement at the final follow-up. DFMCWO is an
      effective treatment to treat osteoarthritic symptomatology, delay degenerative
      progression and avoid knee replacement in valgus knees at mid-term follow-up.

PMID- 29322907
TI  - "Turn laterally to the left!". The need for uniform C-arm communication
      terminology during orthopaedic trauma surgery.
AB  - To avoid disturbed teamwork, unnecessary radiation exposure, and procedural
      delays, we designed and tested a uniform communication language for use in
      fluoroscopy-assisted surgical procedures. Input of surgeons and radiographers was
      used to create a set of commands. The potential benefit of this terminology was
      explored in an experimental setting. There was a tremendous diversity in the
      currently used terminology. Use of the newly designed terminology showed a
      reduction of procedural time and amount of images needed. Our first standardized
      Dutch language terminology can reduce total fluoroscopy time, number of images
      acquired, and potentially radiation exposure. For Dutch speaking colleagues, the
      developed terminology is freely available for use in their OR.

PMID- 29322908
TI  - Prevalence of Bilateral Involvement in Patients with Discoid Lateral Meniscus : a
      Systematic Literature Review.
AB  - We assessed the prevalence of bilateral discoid lateral meniscus (BDLM), as well
      as its subtypes, among patients with symptomatic DLM. Medline, Cochrane, EMBASE,
      and Google Scholar were searched until September 18, 2015. All studies evaluating
      patients with BDLM who underwent MRI, macroscopic observation, and/or arthroscopy
      for the diagnosis of discoid meniscus/menisci were included. Eight clinical
      studies with a total of 583 DLM patients examined including 103 cadavers. There
      was a male predominance and average age of BDLM patients ranged from 10.4 to 39.9
      years. The reported prevalence was higher in East Asian countries (72.7 to 97%)
      than rest of the world (6.8 to 90%). Homotypes were much more common than
      heterotype, and ranged from 82.9 to 91.7% of all BDLM patients. The actual
      prevalence of BDLM is likely higher. The findings provide a glimpse of the wide
      spread this disorder potentially has in East Asia.

PMID- 29322909
TI  - Operative versus Non operative treatment of displaced intraarticular fracture of
      calcaneum: a meta-analysis of randomized controlled trials.
AB  - Various studies comparing operative and non-operative intervention for displaced
      intrarticular calcaneal fractures have reported conflicting findings in the past.
      The objective of this meta-analysis was to compare the efficacy and safety of
      open reduction and internal fixation (ORIF) vis-a-vis conservative management.
      Relevant randomized controlled trials (RCTs) comparing operative and non
      operative intervention for displaced intraarticular calcaneal fractures were
      assessed and included in this meta-analysis. Data was extracted independently and
      methodological quality was further assessed. The inclusion criteria of this meta
      analysis were: randomized controlled trials comparing operative with non
      operative intervention for displaced intra-articular fractures of calcaneum and
      reporting atleast one of the main outcomes as failure to resume pre-injury work,
      residual pain and other complications. Eight randomized controlled trials
      fulfilled the criteria for this meta-analysis. Pooled results showed that
      patients managed conservatively failed to resume pre-injury work (RR 0.60, 95% CI
      = 0.37-0.98, P = 0.04). However operative intervention was associated with more
      complications (RR 1.74, 95% CI = 1.28 to 2.37, P = 0.0005). There was no
      statistically significant difference in residual pain (RR 0.73 95% CI = 0.40
      1.36, P = 0.33) and reoperation (RR = 0.75, 95% CI = 0.48-1.16, P = 0.20) between
      the two groups. Surgery can benefit patients with calcaneal fracture and
      increases their likelihood to resume pre-injury work. However, the complication
      rates are significantly higher in the operative group. Since the included trials
      have used different scores to measure patient outcomes, hence little effective
      data could.

PMID- 29322910
TI  - Flexible memory-alloy instrumentation for unilateral transpedicular kyphoplasty
      and guided cement augmentation of the thoracic spine.
AB  - The purpose of this novel study was to investigate the feasibility of unilateral
      transpedicular balloon kyphoplasty particularly of the upper thoracic vertebrae
      using an 11- gauge balloon and cement inserter, and to study the morphological
      parameters of the thoracic spine pedicles. We used four fresh frozen cadaveric
      thoracic spines with intact rib cages and skin for kyphoplasty from T1 to T12
      vertebrae under C-arm fluoroscopy. The most limiting width of the pedicles 2.46+/
      0.32mm was in the middle levels (T5-T8). The absolute minimum height of the
      pedicles was at T1 (3.80-3.87mm). All regions of the vertebral body were
      effectively targeted for cement augmentation. The average cement load of all the
      vertebral bodies was 43,22%. Using the kyphoplasty technique in combination with
      the pre-bent 11mm memory-alloy cement inserter allowed targeting of the desired
      position of the vertebral body for effective vertebral body cement augmentation.

PMID- 29322911
TI  - Comparison of lumbar pedicular dynamic stabilisation systems versus fusion for
      the treatment of lumbar degenerative disc disease: A meta-analysis.
AB  - This study aimed to systematically compare the safety, effectiveness and
      radiological changes after lumbar pedicular dynamic stabilisation systems and
      fusion to treat lumbar degenerative disc disease . All studies that were
      performed to compare various lumbar pedicular dynamic stabilisation systems with
      any lumbar fusion to treat lumbar degenerative disc disease and were published
      until April 30, 2015 were acquired through a comprehensive search in various
      databases. A meta-analysis was performed after the methodological qualities of
      trials were assessed and after data were extracted. Sixteen trials with 881
      patients with a short-term follow-up (within 2 years) and a middle-term follow-up
      (2 to 4 years) were identified. Patients treated with lumbar pedicular dynamic
      stabilisation systems experienced more significant advantages in terms of
      operation time, intra-operative blood loss, complications and adjacent segment
      degeneration/disease development than those treated with lumbar fusion. The two
      groups did not significantly differ in terms of improvement in Oswestry
      Disability Index, visual analogue scale scores, satisfaction rate of operation
      and range of motion of adjacent segments. Lumbar pedicular dynamic stabilisation
      systems is superior to lumbar fusion to some extent, although some of its
      advantages have yet to be verified and compared with those of lumbar fusion.
      However, the two interventions were not significantly different in terms of
      relief in symptoms, functional recovery and motion preservation. Thus, lumbar
      pedicular dynamic stabilisation systems is recommended for its safety. A prudent
      attitude is necessary to choose between these interventions on the basis of
      effectiveness and changes in adjacent segments before a large-scale and long-term
      follow-up study can be performed.

PMID- 29322912
TI  - Usage of cell nomenclature in biomedical literature.
AB  - BACKGROUND: Cell lines and cell types are extensively studied in biomedical
      research yielding to a significant amount of publications each year. Identifying
      cell lines and cell types precisely in publications is crucial for science
      reproducibility and knowledge integration. There are efforts for standardisation
      of the cell nomenclature based on ontology development to support FAIR principles
      of the cell knowledge. However, it is important to analyse the usage of cell
      nomenclature in publications at a large scale for understanding the level of
      uptake of cell nomenclature in literature by scientists. In this study, we
      analyse the usage of cell nomenclature, both in Vivo, and in Vitro in biomedical
      literature by using text mining methods and present our results. RESULTS: We
      identified 59% of the cell type classes in the Cell Ontology and 13% of the cell
      line classes in the Cell Line Ontology in the literature. Our analysis showed
      that cell line nomenclature is much more ambiguous compared to the cell type
      nomenclature. However, trends indicate that standardised nomenclature for cell
      lines and cell types are being increasingly used in publications by the
      scientists. CONCLUSIONS: Our findings provide an insight to understand how
      experimental cells are described in publications and may allow for an improved
      standardisation of cell type and cell line nomenclature as well as can be
      utilised to develop efficient text mining applications on cell types and cell
      lines. All data generated in this study is available at
      https://github.com/shenay/CellNomenclatureStudy.

PMID- 29322913
TI  - Cell type discovery and representation in the era of high-content single cell
      phenotyping.
AB  - BACKGROUND: A fundamental characteristic of multicellular organisms is the
      specialization of functional cell types through the process of differentiation.
      These specialized cell types not only characterize the normal functioning of
      different organs and tissues, they can also be used as cellular biomarkers of a
      variety of different disease states and therapeutic/vaccine responses. In order
      to serve as a reference for cell type representation, the Cell Ontology has been
      developed to provide a standard nomenclature of defined cell types for
      comparative analysis and biomarker discovery. Historically, these cell types have
      been defined based on unique cellular shapes and structures, anatomic locations,
      and marker protein expression. However, we are now experiencing a revolution in
      cellular characterization resulting from the application of new high-throughput,
      high-content cytometry and sequencing technologies. The resulting explosion in
      the number of distinct cell types being identified is challenging the current
      paradigm for cell type definition in the Cell Ontology. RESULTS: In this paper,
      we provide examples of state-of-the-art cellular biomarker characterization using
      high-content cytometry and single cell RNA sequencing, and present strategies for
      standardized cell type representations based on the data outputs from these
      cutting-edge technologies, including "context annotations" in the form of
      standardized experiment metadata about the specimen source analyzed and marker
      genes that serve as the most useful features in machine learning-based cell type
      classification models. We also propose a statistical strategy for comparing new
      experiment data to these standardized cell type representations. CONCLUSION: The
      advent of high-throughput/high-content single cell technologies is leading to an
      explosion in the number of distinct cell types being identified. It will be
      critical for the bioinformatics community to develop and adopt data standard
      conventions that will be compatible with these new technologies and support the
      data representation needs of the research community. The proposals enumerated
      here will serve as a useful starting point to address these challenges.

PMID- 29322914
TI  - Cell ontology in an age of data-driven cell classification.
AB  - BACKGROUND: Data-driven cell classification is becoming common and is now being
      implemented on a massive scale by projects such as the Human Cell Atlas. The
      scale of these efforts poses a challenge. How can the results be made searchable
      and accessible to biologists in general? How can they be related back to the rich
      classical knowledge of cell-types, anatomy and development? How will data from
      the various types of single cell analysis be made cross-searchable? Structured
      annotation with ontology terms provides a potential solution to these problems.
      In turn, there is great potential for using the outputs of data-driven cell
      classification to structure ontologies and integrate them with data-driven cell
      query systems. RESULTS: Focusing on examples from the mouse retina and Drosophila
      olfactory system, I present worked examples illustrating how formalization of
      cell ontologies can enhance querying of data-driven cell-classifications and how
      ontologies can be extended by integrating the outputs of data-driven cell
      classifications. CONCLUSIONS: Annotation with ontology terms can play an
      important role in making data driven classifications searchable and query-able,
      but fulfilling this potential requires standardized formal patterns for
      structuring ontologies and annotations and for linking ontologies to the outputs
      of data-driven classification.

PMID- 29322915
TI  - Comparison, alignment, and synchronization of cell line information between CLO
      and EFO.
AB  - BACKGROUND: The Experimental Factor Ontology (EFO) is an application ontology
      driven by experimental variables including cell lines to organize and describe
      the diverse experimental variables and data resided in the EMBL-EBI resources.
      The Cell Line Ontology (CLO) is an OBO community-based ontology that contains
      information of immortalized cell lines and relevant experimental components. EFO
      integrates and extends ontologies from the bio-ontology community to drive a
      number of practical applications. It is desirable that the community shares
      design patterns and therefore that EFO reuses the cell line representation from
      the Cell Line Ontology (CLO). There are, however, challenges to be addressed when
      developing a common ontology design pattern for representing cell lines in both
      EFO and CLO. RESULTS: In this study, we developed a strategy to compare and map
      cell line terms between EFO and CLO. We examined Cellosaurus resources for EFO
      CLO cross-references. Text labels of cell lines from both ontologies were
      verified by biological information axiomatized in each source. The study resulted
      in the identification 873 EFO-CLO aligned and 344 EFO unique immortalized
      permanent cell lines. All of these cell lines were updated to CLO and the cell
      line related information was merged. A design pattern that integrates EFO and CLO
      was also developed. CONCLUSION: Our study compared, aligned, and synchronized the
      cell line information between CLO and EFO. The final updated CLO will be examined
      as the candidate ontology to import and replace eligible EFO cell line classes
      thereby supporting the interoperability in the bio-ontology domain. Our mapping
      pipeline illustrates the use of ontology in aiding biological data
      standardization and integration through the biological and semantics content of
      cell lines.

PMID- 29322916
TI  - Cells in experimental life sciences - challenges and solution to the rapid
      evolution of knowledge.
AB  - Cell cultures used in biomedical experiments come in the form of both sample
      biopsy primary cells, and maintainable immortalised cell lineages. The rise of
      bioinformatics and high-throughput technologies has led us to the requirement of
      ontology representation of cell types and cell lines. The Cell Ontology (CL) and
      Cell Line Ontology (CLO) have long been established as reference ontologies in
      the OBO framework. We have compiled a series of the challenges and the proposals
      of solutions in this CELLS (Cells in ExperimentaL Life Sciences) thematic series
      that cover the grounds of standing issues and the directions, which were
      discussed in the First International Workshop on CELLS at the the International
      Conference on Biomedical Ontology (ICBO). This workshop focused on the extension
      of the current CL and CLO to cover a wider set of biological questions and
      challenges needing semantic infrastructure for information modeling. We discussed
      data-driven use cases that leverage linkage of CL, CLO and other bio-ontologies.
      This is an established approach in data-driven ontologies such as the
      Experimental Factor Ontology (EFO), and the Ontology for Biomedical Investigation
      (OBI). The First International Workshop on CELLS at the International Conference
      on Biomedical Ontology has brought together experimental biologists and
      biomedical ontologists to discuss solutions to organizing and representing the
      rapidly evolving knowledge gained from experimental cells. The workshop has
      successfully identified the areas of challenge, and the gap in connecting the two
      domains of knowledge. The outcome of this workshop yielded practical
      implementation plans to filled in this gap.This CELLS workshop also provided a
      venue for panel discussions of innovative solutions as well as challenges in the
      development and applications of biomedical ontologies to represent and analyze
      experimental cell data.

PMID- 29322917
TI  - Identification of natural antimicrobial peptides from bacteria through
      metagenomic and metatranscriptomic analysis of high-throughput transcriptome data
      of Taiwanese oolong teas.
AB  - BACKGROUND: Anti-microbial peptides (AMPs), naturally encoded by genes and
      generally containing 12-100 amino acids, are crucial components of the innate
      immune system and can protect the host from various pathogenic bacteria and
      viruses. In recent years, the widespread use of antibiotics has resulted in the
      rapid growth of antibiotic-resistant microorganisms that often induce critical
      infection and pathogenesis. Recently, the advent of high-throughput technologies
      has led molecular biology into a data surge in both the amount and scope of data.
      For instance, next-generation sequencing technology has been applied to generate
      large-scale sequencing reads from foods, water, soil, air, and specimens to
      identify microbiota and their functions based on metagenomics and
      metatranscriptomics, respectively. In addition, oolong tea is partially fermented
      and is the most widely produced tea in Taiwan. Many studies have shown the
      benefits of oolong tea in inhibiting obesity, reducing dental plaque deposition,
      antagonizing allergic immune responses, and alleviating the effects of aging.
      However, the microbes and their functions present in oolong tea remain unknown.
      RESULTS: To understand the relationship between Taiwanese oolong teas and
      bacterial communities, we designed a novel bioinformatics scheme to identify AMPs
      and their functional types based on metagenomics and metatranscriptomic analysis
      of high-throughput transcriptome data. Four types of oolong teas (Dayuling tea,
      Alishan tea, Jinxuan tea, and Oriental Beauty tea) were subjected to 16S
      ribosomal DNA and total RNA extraction and sequencing. Metagenomics analysis
      results revealed that Oriental Beauty tea exhibited greater bacterial diversity
      than other teas. The most common bacterial families across all tea types were
      Bacteroidaceae (21.7%), Veillonellaceae (22%), and Fusobacteriaceae (12.3%).
      Metatranscriptomics analysis results revealed that the dominant bacteria species
      across all tea types were Escherichia coli, Bacillus subtilis, and
      Chryseobacterium sp. StRB126, which were subjected to further functional
      analysis. A total of 8194 (6.5%), 26,220 (6.1%), 5703 (5.8%), and 106,183 (7.8%)
      reads could be mapped to AMPs. CONCLUSION: We found that the distribution of anti
      gram-positive and anti-gram-negative AMPs is highly correlated with the
      distribution of gram-positive and gram-negative bacteria in Taiwanese oolong tea
      samples.

PMID- 29322918
TI  - A linear programming computational framework integrates phosphor-proteomics and
      prior knowledge to predict drug efficacy.
AB  - BACKGROUND: In recent years, the integration of 'omics' technologies, high
      performance computation, and mathematical modeling of biological processes marks
      that the systems biology has started to fundamentally impact the way of
      approaching drug discovery. The LINCS public data warehouse provides detailed
      information about cell responses with various genetic and environmental
      stressors. It can be greatly helpful in developing new drugs and therapeutics, as
      well as improving the situations of lacking effective drugs, drug resistance and
      relapse in cancer therapies, etc. RESULTS: In this study, we developed a Ternary
      status based Integer Linear Programming (TILP) method to infer cell-specific
      signaling pathway network and predict compounds' treatment efficacy. The novelty
      of our study is that phosphor-proteomic data and prior knowledge are combined for
      modeling and optimizing the signaling network. To test the power of our approach,
      a generic pathway network was constructed for a human breast cancer cell line
      MCF7; and the TILP model was used to infer MCF7-specific pathways with a set of
      phosphor-proteomic data collected from ten representative small molecule chemical
      compounds (most of them were studied in breast cancer treatment). Cross
      validation indicated that the MCF7-specific pathway network inferred by TILP were
      reliable predicting a compound's efficacy. Finally, we applied TILP to re
      optimize the inferred cell-specific pathways and predict the outcomes of five
      small compounds (carmustine, doxorubicin, GW-8510, daunorubicin, and verapamil),
      which were rarely used in clinic for breast cancer. In the simulation, the
      proposed approach facilitates us to identify a compound's treatment efficacy
      qualitatively and quantitatively, and the cross validation analysis indicated
      good accuracy in predicting effects of five compounds. CONCLUSIONS: In summary,
      the TILP model is useful for discovering new drugs for clinic use, and also
      elucidating the potential mechanisms of a compound to targets.

PMID- 29322919
TI  - Hadamard Kernel SVM with applications for breast cancer outcome predictions.
AB  - BACKGROUND: Breast cancer is one of the leading causes of deaths for women. It is
      of great necessity to develop effective methods for breast cancer detection and
      diagnosis. Recent studies have focused on gene-based signatures for outcome
      predictions. Kernel SVM for its discriminative power in dealing with small sample
      pattern recognition problems has attracted a lot attention. But how to select or
      construct an appropriate kernel for a specified problem still needs further
      investigation. RESULTS: Here we propose a novel kernel (Hadamard Kernel) in
      conjunction with Support Vector Machines (SVMs) to address the problem of breast
      cancer outcome prediction using gene expression data. Hadamard Kernel outperform
      the classical kernels and correlation kernel in terms of Area under the ROC Curve
      (AUC) values where a number of real-world data sets are adopted to test the
      performance of different methods. CONCLUSIONS: Hadamard Kernel SVM is effective
      for breast cancer predictions, either in terms of prognosis or diagnosis. It may
      benefit patients by guiding therapeutic options. Apart from that, it would be a
      valuable addition to the current SVM kernel families. We hope it will contribute
      to the wider biology and related communities.

PMID- 29322920
TI  - Investigation and identification of functional post-translational modification
      sites associated with drug binding and protein-protein interactions.
AB  - BACKGROUND: Protein post-translational modification (PTM) plays an essential role
      in various cellular processes that modulates the physical and chemical
      properties, folding, conformation, stability and activity of proteins, thereby
      modifying the functions of proteins. The improved throughput of mass spectrometry
      (MS) or MS/MS technology has not only brought about a surge in proteome-scale
      studies, but also contributed to a fruitful list of identified PTMs. However,
      with the increase in the number of identified PTMs, perhaps the more crucial
      question is what kind of biological mechanisms these PTMs are involved in. This
      is particularly important in light of the fact that most protein-based
      pharmaceuticals deliver their therapeutic effects through some form of PTM. Yet,
      our understanding is still limited with respect to the local effects and
      frequency of PTM sites near pharmaceutical binding sites and the interfaces of
      protein-protein interaction (PPI). Understanding PTM's function is critical to
      our ability to manipulate the biological mechanisms of protein. RESULTS: In this
      study, to understand the regulation of protein functions by PTMs, we mapped
      25,835 PTM sites to proteins with available three-dimensional (3D) structural
      information in the Protein Data Bank (PDB), including 1785 modified PTM sites on
      the 3D structure. Based on the acquired structural PTM sites, we proposed to use
      five properties for the structural characterization of PTM substrate sites: the
      spatial composition of amino acids, residues and side-chain orientations
      surrounding the PTM substrate sites, as well as the secondary structure, division
      of acidity and alkaline residues, and solvent-accessible surface area. We further
      mapped the structural PTM sites to the structures of drug binding and PPI sites,
      identifying a total of 1917 PTM sites that may affect PPI and 3951 PTM sites
      associated with drug-target binding. An integrated analytical platform (CruxPTM),
      with a variety of methods and online molecular docking tools for exploring the
      structural characteristics of PTMs, is presented. In addition, all tertiary
      structures of PTM sites on proteins can be visualized using the JSmol program.
      CONCLUSION: Resolving the function of PTM sites is important for understanding
      the role that proteins play in biological mechanisms. Our work attempted to
      delineate the structural correlation between PTM sites and PPI or drug-target
      binding. CurxPTM could help scientists narrow the scope of their PTM research and
      enhance the efficiency of PTM identification in the face of big proteome data.
      CruxPTM is now available at http://csb.cse.yzu.edu.tw/CruxPTM/ .

PMID- 29322921
TI  - Tensor decomposition-based unsupervised feature extraction identifies candidate
      genes that induce post-traumatic stress disorder-mediated heart diseases.
AB  - BACKGROUND: Although post-traumatic stress disorder (PTSD) is primarily a mental
      disorder, it can cause additional symptoms that do not seem to be directly
      related to the central nervous system, which PTSD is assumed to directly affect.
      PTSD-mediated heart diseases are some of such secondary disorders. In spite of
      the significant correlations between PTSD and heart diseases, spatial separation
      between the heart and brain (where PTSD is primarily active) prevents researchers
      from elucidating the mechanisms that bridge the two disorders. Our purpose was to
      identify genes linking PTSD and heart diseases. METHODS: In this study, gene
      expression profiles of various murine tissues observed under various types of
      stress or without stress were analyzed in an integrated manner using tensor
      decomposition (TD). RESULTS: Based upon the obtained features, ~ 400 genes were
      identified as candidate genes that may mediate heart diseases associated with
      PTSD. Various gene enrichment analyses supported biological reliability of the
      identified genes. Ten genes encoding protein-, DNA-, or mRNA-interacting proteins
      ILF2, ILF3, ESR1, ESR2, RAD21, HTT, ATF2, NR3C1, TP53, and TP63-were found to be
      likely to regulate expression of most of these ~ 400 genes and therefore are
      candidate primary genes that cause PTSD-mediated heart diseases. Approximately
      400 genes in the heart were also found to be strongly affected by various drugs
      whose known adverse effects are related to heart diseases and/or fear memory
      conditioning; these data support the reliability of our findings. CONCLUSIONS: TD
      based unsupervised feature extraction turned out to be a useful method for gene
      selection and successfully identified possible genes causing PTSD-mediated heart
      diseases.

PMID- 29322922
TI  - Analysis of viral diversity for vaccine target discovery.
AB  - BACKGROUND: Viral vaccine target discovery requires understanding the diversity
      of both the virus and the human immune system. The readily available and rapidly
      growing pool of viral sequence data in the public domain enable the
      identification and characterization of immune targets relevant to adaptive
      immunity. A systematic bioinformatics approach is necessary to facilitate the
      analysis of such large datasets for selection of potential candidate vaccine
      targets. RESULTS: This work describes a computational methodology to achieve this
      analysis, with data of dengue, West Nile, hepatitis A, HIV-1, and influenza A
      viruses as examples. Our methodology has been implemented as an analytical
      pipeline that brings significant advancement to the field of reverse vaccinology,
      enabling systematic screening of known sequence data in nature for identification
      of vaccine targets. This includes key steps (i) comprehensive and extensive
      collection of sequence data of viral proteomes (the virome), (ii) data cleaning,
      (iii) large-scale sequence alignments, (iv) peptide entropy analysis, (v) intra-
      and inter-species variation analysis of conserved sequences, including human
      homology analysis, and (vi) functional and immunological relevance analysis.
      CONCLUSION: These steps are combined into the pipeline ensuring that a more
      refined process, as compared to a simple evolutionary conservation analysis, will
      facilitate a better selection of vaccine targets and their prioritization for
      subsequent experimental validation.

PMID- 29322923
TI  - A polynomial based model for cell fate prediction in human diseases.
AB  - BACKGROUND: Cell fate regulation directly affects tissue homeostasis and human
      health. Research on cell fate decision sheds light on key regulators, facilitates
      understanding the mechanisms, and suggests novel strategies to treat human
      diseases that are related to abnormal cell development. RESULTS: In this study,
      we proposed a polynomial based model to predict cell fate. This model was derived
      from Taylor series. As a case study, gene expression data of pancreatic cells
      were adopted to test and verify the model. As numerous features (genes) are
      available, we employed two kinds of feature selection methods, i.e. correlation
      based and apoptosis pathway based. Then polynomials of different degrees were
      used to refine the cell fate prediction function. 10-fold cross-validation was
      carried out to evaluate the performance of our model. In addition, we analyzed
      the stability of the resultant cell fate prediction model by evaluating the
      ranges of the parameters, as well as assessing the variances of the predicted
      values at randomly selected points. Results show that, within both the two
      considered gene selection methods, the prediction accuracies of polynomials of
      different degrees show little differences. Interestingly, the linear polynomial
      (degree 1 polynomial) is more stable than others. When comparing the linear
      polynomials based on the two gene selection methods, it shows that although the
      accuracy of the linear polynomial that uses correlation analysis outcomes is a
      little higher (achieves 86.62%), the one within genes of the apoptosis pathway is
      much more stable. CONCLUSIONS: Considering both the prediction accuracy and the
      stability of polynomial models of different degrees, the linear model is a
      preferred choice for cell fate prediction with gene expression data of pancreatic
      cells. The presented cell fate prediction model can be extended to other cells,
      which may be important for basic research as well as clinical study of cell
      development related diseases.

PMID- 29322924
TI  - Detecting causality from short time-series data based on prediction of
      topologically equivalent attractors.

PMID- 29322925
TI  - Subtype identification from heterogeneous TCGA datasets on a genomic scale by
      multi-view clustering with enhanced consensus.
AB  - BACKGROUND: The Cancer Genome Atlas (TCGA) has collected transcriptome, genome
      and epigenome information for over 20 cancers from thousands of patients. The
      availability of these diverse data types makes it necessary to combine these data
      to capture the heterogeneity of biological processes and phenotypes and further
      identify homogeneous subtypes for cancers such as breast cancer. Many multi-view
      clustering approaches are proposed to discover clusters across different data
      types. The problem is challenging when different data types show poor agreement
      of clustering structure. RESULTS: In this work, we first propose a multi-view
      clustering approach with consensus (CMC), which tries to find consensus kernels
      among views by using Hilbert Schmidt Independence Criterion. To tackle the
      problem when poor agreement among views exists, we further propose a multi-view
      clustering approach with enhanced consensus (ECMC) to solve this problem by
      decomposing the kernel information in each view into a consensus part and a
      disagreement part. The consensus parts for different views are supposed to be
      similar, and the disagreement parts should be independent with the consensus
      parts. Both the CMC and ECMC models can be solved by alternative updating with
      semi-definite programming. Our experiments on both simulation datasets and real
      world benchmark datasets show that ECMC model could achieve higher clustering
      accuracies than other state-of-art multi-view clustering approaches. We also
      apply the ECMC model to integrate mRNA expression, DNA methylation and microRNA
      (miRNA) expression data for five cancer data sets, and the survival analysis show
      that our ECMC model outperforms other methods when identifying cancer subtypes.
      By Fisher's combination test method, we found that three computed subtypes
      roughly correspond to three known breast cancer subtypes including luminal B,
      HER2 and basal-like subtypes. CONCLUSION: Integrating heterogeneous TCGA datasets
      by our proposed multi-view clustering approach ECMC could effectively identify
      cancer subtypes.

PMID- 29322926
TI  - Construction and analysis of gene-gene dynamics influence networks based on a
      Boolean model.
AB  - BACKGROUND: Identification of novel gene-gene relations is a crucial issue to
      understand system-level biological phenomena. To this end, many methods based on
      a correlation analysis of gene expressions or structural analysis of molecular
      interaction networks have been proposed. They have a limitation in identifying
      more complicated gene-gene dynamical relations, though. RESULTS: To overcome this
      limitation, we proposed a measure to quantify a gene-gene dynamical influence
      (GDI) using a Boolean network model and constructed a GDI network to indicate
      existence of a dynamical influence for every ordered pair of genes. It represents
      how much a state trajectory of a target gene is changed by a knockout mutation
      subject to a source gene in a gene-gene molecular interaction (GMI) network.
      Through a topological comparison between GDI and GMI networks, we observed that
      the former network is denser than the latter network, which implies that there
      exist many gene pairs of dynamically influencing but molecularly non-interacting
      relations. In addition, a larger number of hub genes were generated in the GDI
      network. On the other hand, there was a correlation between these networks such
      that the degree value of a node was positively correlated to each other. We
      further investigated the relationships of the GDI value with structural
      properties and found that there are negative and positive correlations with the
      length of a shortest path and the number of paths, respectively. In addition, a
      GDI network could predict a set of genes whose steady-state expression is
      affected in E. coli gene-knockout experiments. More interestingly, we found that
      the drug-targets with side-effects have a larger number of outgoing links than
      the other genes in the GDI network, which implies that they are more likely to
      influence the dynamics of other genes. Finally, we found biological evidences
      showing that the gene pairs which are not molecularly interacting but dynamically
      influential can be considered for novel gene-gene relationships. CONCLUSION:
      Taken together, construction and analysis of the GDI network can be a useful
      approach to identify novel gene-gene relationships in terms of the dynamical
      influence.

PMID- 29322928
TI  - Constraint-based perturbation analysis with cluster Newton method: a case study
      of personalized parameter estimations with irinotecan whole-body physiologically
      based pharmacokinetic model.
AB  - BACKGROUND: Drug development considering individual varieties among patients
      becomes crucial to improve clinical development success rates and save healthcare
      costs. As a useful tool to predict individual phenomena and correlations among
      drug characteristics and individual varieties, recently, whole-body
      physiologically based pharmacokinetic (WB- PBPK) models are getting more
      attention. WB-PBPK models generally have a lot of drug-related parameters that
      need to be estimated, and the estimations are difficult because the observed data
      are limited. Furthermore, parameter estimation in WB-PBPK models may cause
      overfitting when applying to individual clinical data such as urine/feces drug
      excretion for each patient in which Cluster Newton Method (CNM) is applicable for
      parameter estimation. In order to solve this issue, we came up with the idea of
      constraint-based perturbation analysis of the CNM. The effectiveness of our
      approach is demonstrated in the case of irinotecan WB-PBPK model using common
      organ-specific tissue-plasma partition coefficients (Kp) among the patients as
      constraints in WB-PBPK parameter estimation. RESULTS: We find strong correlations
      between age, renal clearance and liver functions in irinotecan WB-PBPK model with
      personalized physiological parameters by observing the distributions of optimized
      values of strong convergence drug-related parameters using constraint-based
      perturbation analysis on CNM. The constraint-based perturbation analysis consists
      of the following three steps: (1) Estimation of all drug-related parameters for
      each patient; the parameters include organ-specific Kp. (2) Fixing suitable
      values of Kp for each organ among all patients identically. (3) Re-estimation of
      all drug-related parameters other than Kp by using the fixed values of Kp as
      constraints of CNM. CONCLUSIONS: Constraint-based perturbation analysis could
      yield new findings when using CNM with appropriate constraints. This method is a
      new technique to find suitable values and important insights that are masked by
      CNM without constraints.

PMID- 29322927
TI  - CPredictor3.0: detecting protein complexes from PPI networks with expression data
      and functional annotations.
AB  - BACKGROUND: Effectively predicting protein complexes not only helps to understand
      the structures and functions of proteins and their complexes, but also is useful
      for diagnosing disease and developing new drugs. Up to now, many methods have
      been developed to detect complexes by mining dense subgraphs from static protein
      protein interaction (PPI) networks, while ignoring the value of other biological
      information and the dynamic properties of cellular systems. RESULTS: In this
      paper, based on our previous works CPredictor and CPredictor2.0, we present a new
      method for predicting complexes from PPI networks with both gene expression data
      and protein functional annotations, which is called CPredictor3.0. This new
      method follows the viewpoint that proteins in the same complex should roughly
      have similar functions and are active at the same time and place in cellular
      systems. We first detect active proteins by using gene express data of different
      time points and cluster proteins by using gene ontology (GO) functional
      annotations, respectively. Then, for each time point, we do set intersections
      with one set corresponding to active proteins generated from expression data and
      the other set corresponding to a protein cluster generated from functional
      annotations. Each resulting unique set indicates a cluster of proteins that have
      similar function(s) and are active at that time point. Following that, we map
      each cluster of active proteins of similar function onto a static PPI network,
      and get a series of induced connected subgraphs. We treat these subgraphs as
      candidate complexes. Finally, by expanding and merging these candidate complexes,
      the predicted complexes are obtained. We evaluate CPredictor3.0 and compare it
      with a number of existing methods on several PPI networks and benchmarking
      complex datasets. The experimental results show that CPredictor3.0 achieves the
      highest F1-measure, which indicates that CPredictor3.0 outperforms these existing
      method in overall. CONCLUSION: CPredictor3.0 can serve as a promising tool of
      protein complex prediction.

PMID- 29322929
TI  - Ontology-based systematic representation and analysis of traditional Chinese
      drugs against rheumatism.
AB  - BACKGROUND: Rheumatism represents any disease condition marked with inflammation
      and pain in the joints, muscles, or connective tissues. Many traditional Chinese
      drugs have been used for a long time to treat rheumatism. However, a
      comprehensive information source for these drugs is still missing, and their anti
      rheumatism mechanisms remain unclear. An ontology for anti-rheumatism traditional
      Chinese drugs would strongly support the representation, analysis, and
      understanding of these drugs. RESULTS: In this study, we first systematically
      collected reported information about 26 traditional Chinese decoction pieces
      drugs, including their chemical ingredients and adverse events (AEs). By mostly
      reusing terms from existing ontologies (e.g., TCMDPO for traditional Chinese
      medicines, NCBITaxon for taxonomy, ChEBI for chemical elements, and OAE for
      adverse events) and making semantic axioms linking different entities, we
      developed the Ontology of Chinese Medicine for Rheumatism (OCMR) that includes
      over 3000 class terms. Our OCMR analysis found that these 26 traditional Chinese
      decoction pieces are made from anatomic entities (e.g., root and stem) from 3
      Bilateria animals and 23 Mesangiospermae plants. Anti-inflammatory and
      antineoplastic roles are important for anti-rheumatism drugs. Using the total of
      555 unique ChEBI chemical entities identified from these drugs, our ChEBI-based
      classification analysis identified 18 anti-inflammatory, 33 antineoplastic
      chemicals, and 9 chemicals (including 3 diterpenoids and 3 triterpenoids) having
      both anti-inflammatory and antineoplastic roles. Furthermore, our study detected
      22 diterpenoids and 23 triterpenoids, including 16 pentacyclic triterpenoids that
      are likely bioactive against rheumatism. Six drugs were found to be associated
      with 184 unique AEs, including three AEs (i.e., dizziness, nausea and vomiting,
      and anorexia) each associated with 5 drugs. Several chemical entities are
      classified as neurotoxins (e.g., diethyl phthalate) and allergens (e.g.,
      eugenol), which may explain the formation of some TCD AEs. The OCMR could be
      efficiently queried for useful information using SPARQL scripts. CONCLUSIONS: The
      OCMR ontology was developed to systematically represent 26 traditional anti
      rheumatism Chinese drugs and their related information. The OCMR analysis
      identified possible anti-rheumatism and AE mechanisms of these drugs. Our novel
      ontology-based approach can also be applied to systematic representation and
      analysis of other traditional Chinese drugs.

PMID- 29322930
TI  - Ontological representation, integration, and analysis of LINCS cell line cells
      and their cellular responses.
AB  - BACKGROUND: Aiming to understand cellular responses to different perturbations,
      the NIH Common Fund Library of Integrated Network-based Cellular Signatures
      (LINCS) program involves many institutes and laboratories working on over a
      thousand cell lines. The community-based Cell Line Ontology (CLO) is selected as
      the default ontology for LINCS cell line representation and integration. RESULTS:
      CLO has consistently represented all 1097 LINCS cell lines and included
      information extracted from the LINCS Data Portal and ChEMBL. Using MCF 10A cell
      line cells as an example, we demonstrated how to ontologically model LINCS
      cellular signatures such as their non-tumorigenic epithelial cell type, three
      dimensional growth, latrunculin-A-induced actin depolymerization and apoptosis,
      and cell line transfection. A CLO subset view of LINCS cell lines, named LINCS
      CLOview, was generated to support systematic LINCS cell line analysis and
      queries. In summary, LINCS cell lines are currently associated with 43 cell
      types, 131 tissues and organs, and 121 cancer types. The LINCS-CLO view
      information can be queried using SPARQL scripts. CONCLUSIONS: CLO was used to
      support ontological representation, integration, and analysis of over a thousand
      LINCS cell line cells and their cellular responses.

PMID- 29322931
TI  - Differential responses of innate immunity triggered by different subtypes of
      influenza a viruses in human and avian hosts.
AB  - BACKGROUND: Innate immunity provides first line of defense against viral
      infections. The interactions between hosts and influenza A virus and the response
      of host innate immunity to viral infection are critical determinants for the
      pathogenicity or virulence of influenza A viruses. This study was designed to
      investigate global changes of gene expression and detailed responses of innate
      immune systems in human and avian hosts during the course of infection with
      various subtypes of influenza A viruses, using collected and self-generated
      transcriptome sequencing data from human bronchial epithelial (HBE), human
      tracheobronchial epithelial (HTBE), and A549 cells infected with influenza A
      virus subtypes, namely H1N1, H3N2, H5N1 HALo mutant, and H7N9, and from ileum and
      lung of chicken and quail infected with H5N1, or H5N2. RESULTS: We examined the
      induction of various cytokines and chemokines in human hosts infected with
      different subtypes of influenza A viruses. Type I and III interferons were found
      to be differentially induced with each subtype. H3N2 caused abrupt and the
      strongest response of IFN-beta and IFN-lambda, followed by H1N1 (though much
      weaker), whereas H5N1 HALo mutant and H7N9 induced very minor change in
      expression of type I and III interferons. Similarly, differential responses of
      other innate immunity-related genes were observed, including TMEM173, MX1, OASL,
      IFI6, IFITs, IFITMs, and various chemokine genes like CCL5, CX3CL1, and chemokine
      (C-X-C motif) ligands, SOCS (suppressors of cytokine signaling) genes. Third, the
      replication kinetics of H1N1, H3N2, H5N1 HALo mutant and H7N9 subtypes were
      analyzed, H5N1 HALo mutant was found to have the highest viral replication rate,
      followed by H3N2, and H1N1, while H7N9 had a rate similar to that of H1N1 or H3N2
      though in different host cell type. CONCLUSION: Our study illustrated the
      differential responses of innate immunity to infections of different subtypes of
      influenza A viruses. We found the influenza viruses which induced stronger innate
      immune responses replicate slower than those induces weaker innate immune
      responses. Our study provides important insight into links between the
      differential innate immune responses from hosts and the pathogenicity/ virulence
      of different subtypes of influenza A viruses.

PMID- 29322932
TI  - Identification of prognostic signature in cancer based on DNA methylation
      interaction network.
AB  - BACKGROUND: The identification of prognostic biomarkers for cancer patients is
      essential for cancer research. These days, DNA methylation has been proved to be
      associated with cancer prognosis. However, there are few methods which identify
      the prognostic markers based on DNA methylation data systematically, especially
      considering the interaction among DNA methylation sites. METHODS: In this paper,
      we first evaluated the stabilities of microRNA, mRNA, and DNA methylation data in
      prognosis of cancer. After that, a rank-based method was applied to construct a
      DNA methylation interaction network. In this network, nodes with the largest
      degrees (10% of all the nodes) were selected as hubs. Cox regression was applied
      to select the hubs as prognostic signature. In this prognostic signature, DNA
      methylation levels of each DNA methylation site are correlated with the outcomes
      of cancer patients. After obtaining these prognostic genes, we performed the
      survival analysis in the training group and the test group to verify the
      reliability of these genes. RESULTS: We applied our method in three cancers
      (ovarian cancer, breast cancer and Glioblastoma Multiforme). In all the three
      cancers, there are more common ones of prognostic genes selected from different
      samples in DNA methylation data, compared with gene expression data and miRNA
      expression data, which indicates the DNA methylation data may be more stable in
      cancer prognosis. Power-law distribution fitting suggests that the DNA
      methylation interaction networks are scale-free. And the hubs selected from the
      three networks are all enriched by cancer related pathways. The gene signatures
      were obtained for the three cancers respectively, and survival analysis shows
      they can distinguish the outcomes of tumor patients in both the training data
      sets and test data sets, which outperformed the control signatures. CONCLUSIONS:
      A computational method was proposed to construct DNA methylation interaction
      network and this network could be used to select prognostic signatures in cancer.

PMID- 29322933
TI  - Integrating transcriptional activity in genome-scale models of metabolism.
AB  - BACKGROUND: Genome-scale metabolic models provide an opportunity for rational
      approaches to studies of the different reactions taking place inside the cell.
      The integration of these models with gene regulatory networks is a hot topic in
      systems biology. The methods developed to date focus mostly on resolving the
      metabolic elements and use fairly straightforward approaches to assess the impact
      of genome expression on the metabolic phenotype. RESULTS: We present here a
      method for integrating the reverse engineering of gene regulatory networks into
      these metabolic models. We applied our method to a high-dimensional gene
      expression data set to infer a background gene regulatory network. We then
      compared the resulting phenotype simulations with those obtained by other
      relevant methods. CONCLUSIONS: Our method outperformed the other approaches
      tested and was more robust to noise. We also illustrate the utility of this
      method for studies of a complex biological phenomenon, the diauxic shift in
      yeast.

PMID- 29322934
TI  - Computational analysis reveals the coupling between bistability and the sign of a
      feedback loop in a TGF-beta1 activation model.
AB  - BACKGROUND: Bistable behaviors are prevalent in cell signaling and can be modeled
      by ordinary differential equations (ODEs) with kinetic parameters. A bistable
      switch has recently been found to regulate the activation of transforming growth
      factor-beta1 (TGF-beta1) in the context of liver fibrosis, and an ordinary
      differential equation (ODE) model was published showing that the net activation
      of TGF-beta1 depends on the balance between two antagonistic sub-pathways.
      RESULTS: Through modeling the effects of perturbations that affect both sub
      pathways, we revealed that bistability is coupled with the signs of feedback
      loops in the model. We extended the model to include calcium and Kruppel-like
      factor 2 (KLF2), both regulators of Thrombospondin-1 (TSP1) and Plasmin (PLS).
      Increased levels of extracellular calcium, which alters the TSP1-PLS balance,
      would cause high levels of TGF-beta1, resembling a fibrotic state. KLF2, which
      suppresses production of TSP1 and plasminogen activator inhibitor-1 (PAI1), would
      eradicate bistability and preclude the fibrotic steady-state. Finally, the loop
      PLS - TGF-beta1 - PAI1 had previously been reported as negative feedback, but the
      model suggested a stronger indirect effect of PLS down-regulating PAI1 to produce
      positive (double-negative) feedback in a fibrotic state. Further simulations
      showed that activation of KLF2 was able to restore negative feedback in the PLS -
      TGF-beta1 - PAI1 loop. CONCLUSIONS: Using the TGF-beta1 activation model as a
      case study, we showed that external factors such as calcium or KLF2 can induce or
      eradicate bistability, accompanied by a switch in the sign of a feedback loop
      (PLS - TGF-beta1 - PAI1) in the model. The coupling between bistability and
      positive/negative feedback suggests an alternative way of characterizing a
      dynamical system and its biological implications.

PMID- 29322935
TI  - Classifying cancer genome aberrations by their mutually exclusive effects on
      transcription.
AB  - BACKGROUND: Malignant tumors are typically caused by a conglomeration of genomic
      aberrations-including point mutations, small insertions, small deletions, and
      large copy-number variations. In some cases, specific chemotherapies and targeted
      drug treatments are effective against tumors that harbor certain genomic
      aberrations. However, predictive aberrations (biomarkers) have not been
      identified for many tumor types and treatments. One way to address this problem
      is to examine the downstream, transcriptional effects of genomic aberrations and
      to identify characteristic patterns. Even though two tumors harbor different
      genomic aberrations, the transcriptional effects of those aberrations may be
      similar. These patterns could be used to inform treatment choices. METHODS: We
      used data from 9300 tumors across 25 cancer types from The Cancer Genome Atlas.
      We used supervised machine learning to evaluate our ability to distinguish
      between tumors that had mutually exclusive genomic aberrations in specific genes.
      An ability to accurately distinguish between tumors with aberrations in these
      genes suggested that the genes have a relatively different downstream effect on
      transcription, and vice versa. We compared these findings against prior knowledge
      about signaling networks and drug responses. RESULTS: Our analysis recapitulates
      known relationships in cancer pathways and identifies gene pairs known to predict
      responses to the same treatments. For example, in lung adenocarcinomas, gene
      expression profiles from tumors with somatic aberrations in EGFR or MET were
      negatively correlated with each other, in line with prior knowledge that MET
      amplification causes resistance to EGFR inhibition. In breast carcinomas, we
      observed high similarity between PTEN and PIK3CA, which play complementary roles
      in regulating cellular proliferation. In a pan-cancer analysis, we found that
      genomic aberrations in BRAF and VHL exhibit downstream effects that are clearly
      distinct from other genes. CONCLUSION: We show that transcriptional data offer
      promise as a way to group genomic aberrations according to their downstream
      effects, and these groupings recapitulate known relationships. Our approach shows
      potential to help pharmacologists and clinical trialists narrow the search space
      for candidate gene/drug associations, including for rare mutations, and for
      identifying potential drug-repurposing opportunities.

PMID- 29322936
TI  - Investigation on changes of modularity and robustness by edge-removal mutations
      in signaling networks.
AB  - BACKGROUND: Biological networks consisting of molecular components and
      interactions are represented by a graph model. There have been some studies based
      on that model to analyze a relationship between structural characteristics and
      dynamical behaviors in signaling network. However, little attention has been paid
      to changes of modularity and robustness in mutant networks. RESULTS: In this
      paper, we investigated the changes of modularity and robustness by edge-removal
      mutations in three signaling networks. We first observed that both the modularity
      and robustness increased on average in the mutant network by the edge-removal
      mutations. However, the modularity change was negatively correlated with the
      robustness change. This implies that it is unlikely that both the modularity and
      the robustness values simultaneously increase by the edge-removal mutations.
      Another interesting finding is that the modularity change was positively
      correlated with the degree, the number of feedback loops, and the edge
      betweenness of the removed edges whereas the robustness change was negatively
      correlated with them. We note that these results were consistently observed in
      randomly structure networks. Additionally, we identified two groups of genes
      which are incident to the highly-modularity-increasing and the highly-robustness
      decreasing edges with respect to the edge-removal mutations, respectively, and
      observed that they are likely to be central by forming a connected component of a
      considerably large size. The gene-ontology enrichment of each of these gene
      groups was significantly different from the rest of genes. Finally, we showed
      that the highly-robustness-decreasing edges can be promising edgetic drug
      targets, which validates the usefulness of our analysis. CONCLUSIONS: Taken
      together, the analysis of changes of robustness and modularity against edge
      removal mutations can be useful to unravel novel dynamical characteristics
      underlying in signaling networks.

PMID- 29322937
TI  - Predicting binary, discrete and continued lncRNA-disease associations via a
      unified framework based on graph regression.
AB  - BACKGROUND: In human genomes, long non-coding RNAs (lncRNAs) have attracted more
      and more attention because their dysfunctions are involved in many diseases.
      However, the associations between lncRNAs and diseases (LDA) still remain unknown
      in most cases. While identifying disease-related lncRNAs in vivo is costly,
      computational approaches are promising to not only accelerate the possible
      identification of associations but also provide clues on the underlying mechanism
      of various lncRNA-caused diseases. Former computational approaches usually only
      focus on predicting new associations between lncRNAs having known associations
      with diseases and other lncRNA-associated diseases. They also only work on binary
      lncRNA-disease associations (whether the pair has an association or not), which
      cannot reflect and reveal other biological facts, such as the number of proteins
      involved in LDA or how strong the association is (i.e., the intensity of LDA).
      RESULTS: To address abovementioned issues, we propose a graph regression-based
      unified framework (GRUF). In particular, our method can work on lncRNAs, which
      have no previously known disease association and diseases that have no known
      association with any lncRNAs. Also, instead of only a binary answer for the
      association, our method tries to uncover more biological relationship between a
      pair of lncRNA and disease, which may provide better clues for researchers. We
      compared GRUF with three state-of-the-art approaches and demonstrated the
      superiority of GRUF, which achieves 5%~16% improvement in terms of the area under
      the receiver operating characteristic curve (AUC). GRUF also provides a predicted
      confidence score for the predicted LDA, which reveals the significant correlation
      between the score and the number of RNA-Binding Proteins involved in LDAs.
      Lastly, three out of top-5 LDA candidates generated by GRUF in novel prediction
      are verified indirectly by medical literature and known biological facts.
      CONCLUSIONS: The proposed GRUF has two advantages over existing approaches.
      Firstly, it can be used to work on lncRNAs that have no known disease association
      and diseases that have no known association with any lncRNAs. Secondly, instead
      of providing a binary answer (with or without association), GRUF works for both
      discrete and continued LDA, which help revealing the pathological implications
      between lncRNAs and diseases.

PMID- 29322939
TI  - Public health psychopharmacology: a new research discipline comes of age?
AB  - Research evidence guiding the identification of pragmatic and effective actions
      aimed at improving the selection, availability, affordability and rational
      prescribing of medicines for mental disorders is sparse and inconsistent. In
      order to boost the development of new research, in this commentary we suggest to
      organise and classify all the activities in this area under a common theoretical
      framework and nomenclature, adopting the term 'public health psychopharmacology'.
      Public health psychopharmacology is proposed as a research discipline, based on
      contributions from the fields of regulatory science, health services research and
      implementation science. Implementing the term public health psychopharmacology
      may offer advantages, as the scientific community would be more focused on common
      goals and objectives, with, likely, an increasing body of research evidence of
      practical use.

PMID- 29322938
TI  - MDD-carb: a combinatorial model for the identification of protein carbonylation
      sites with substrate motifs.
AB  - BACKGROUND: Carbonylation, which takes place through oxidation of reactive oxygen
      species (ROS) on specific residues, is an irreversibly oxidative modification of
      proteins. It has been reported that the carbonylation is related to a number of
      metabolic or aging diseases including diabetes, chronic lung disease, Parkinson's
      disease, and Alzheimer's disease. Due to the lack of computational methods
      dedicated to exploring motif signatures of protein carbonylation sites, we were
      motivated to exploit an iterative statistical method to characterize and identify
      carbonylated sites with motif signatures. RESULTS: By manually curating
      experimental data from research articles, we obtained 332, 144, 135, and 140
      verified substrate sites for K (lysine), R (arginine), T (threonine), and P
      (proline) residues, respectively, from 241 carbonylated proteins. In order to
      examine the informative attributes for classifying between carbonylated and non
      carbonylated sites, multifarious features including composition of twenty amino
      acids (AAC), composition of amino acid pairs (AAPC), position-specific scoring
      matrix (PSSM), and positional weighted matrix (PWM) were investigated in this
      study. Additionally, in an attempt to explore the motif signatures of
      carbonylation sites, an iterative statistical method was adopted to detect
      statistically significant dependencies of amino acid compositions between
      specific positions around substrate sites. Profile hidden Markov model (HMM) was
      then utilized to train a predictive model from each motif signature. Moreover,
      based on the method of support vector machine (SVM), we adopted it to construct
      an integrative model by combining the values of bit scores obtained from profile
      HMMs. The combinatorial model could provide an enhanced performance with evenly
      predictive sensitivity and specificity in the evaluation of cross-validation and
      independent testing. CONCLUSION: This study provides a new scheme for exploring
      potential motif signatures at substrate sites of protein carbonylation. The
      usefulness of the revealed motifs in the identification of carbonylated sites is
      demonstrated by their effective performance in cross-validation and independent
      testing. Finally, these substrate motifs were adopted to build an available
      online resource (MDD-Carb, http://csb.cse.yzu.edu.tw/MDDCarb/ ) and are also
      anticipated to facilitate the study of large-scale carbonylated proteomes.

PMID- 29322940
TI  - Mental health capacity building in low and middle income countries: the Emerald
      Programme.

PMID- 29322941
TI  - Persistent activity in a recurrent circuit underlies courtship memory in
      Drosophila.
AB  - Recurrent connections are thought to be a common feature of the neural circuits
      that encode memories, but how memories are laid down in such circuits is not
      fully understood. Here we present evidence that courtship memory in Drosophila
      relies on the recurrent circuit between mushroom body gamma (MBgamma), M6 output,
      and aSP13 dopaminergic neurons. We demonstrate persistent neuronal activity of
      aSP13 neurons and show that it transiently potentiates synaptic transmission from
      MBgamma>M6 neurons. M6 neurons in turn provide input to aSP13 neurons, prolonging
      potentiation of MBgamma>M6 synapses over time periods that match short-term
      memory. These data support a model in which persistent aSP13 activity within a
      recurrent circuit lays the foundation for a short-term memory.

PMID- 29322942
TI  - Purulent pericarditis, an unusual complication of pneumococcal pneumonia: a case
      report.
AB  - Purulent pericarditis has become rare since the advent of antibiotics. Among the
      involved germs, S. pneumoniae remains the most implicated pathogen to evoke in
      principle, especially that prescription of systematic antibiotics for any febrile
      condition can considerably mask the clinical picture. A 36-year-old pregnant
      woman was visiting the emergency department for dyspnea and flu-like syndrom that
      had been going on for a week. The chest X-ray showed a white lung on the left and
      the transthoracic ultrasound revealed a pericardial effusion, resulting in
      pericardial drainage and pleural puncture that allows the evacuation of a
      purulent fluid. S. pneumoniae was identified on the pericardial fluid. Antibiotic
      therapy and resuscitation measures have allowed a good evolution. Even if it has
      become exceptional, pneumococcal pericarditis must not be overlooked since the
      evolution is often favorable in triple conditions: early recognition, prompt
      institution of appropriate antibiotic therapy, and early surgical drainage.

PMID- 29322943
TI  - Ultra-sensitive and selective detection of mercury ion (Hg2+) using free-standing
      silicon nanowire sensors.
AB  - In this paper, ultra-sensitive and highly selective Hg2+ detection in aqueous
      solutions was studied by free-standing silicon nanowire (SiNW) sensors. The all
      around surface of SiNW arrays was functionalized with (3
      Mercaptopropyl)trimethoxysilane serving as Hg2+ sensitive layer. Due to effective
      electrostatic control provided by the free-standing structure, a detection limit
      as low as 1 ppt was obtained. A linear relationship (R 2 = 0.9838) between
      log(CHg2+ ) and a device current change from 1 ppt to 5 ppm was observed.
      Furthermore, the developed SiNW sensor exhibited great selectivity for Hg2+ over
      other heavy metal ions, including Cd2+. Given the extraordinary ability for real
      time Hg2+ detection, the small size and low cost of the SiNW device, it is
      expected to be a potential candidate in field detection of environmentally toxic
      mercury.

PMID- 29322944
TI  - Evidence for nodal superconductivity in a layered compound Ta4Pd3Te16.
AB  - We report an investigation of the London penetration depth [Formula: see text] on
      single crystals of the layered superconductor Ta4Pd3Te16, where the crystal
      structure has quasi-one-dimensional characteristics. A linear temperature
      dependence of [Formula: see text] is observed for [Formula: see text], in
      contrast to the exponential behavior of fully gapped superconductors. This
      indicates the existence of line nodes in the superconducting energy gap. A
      detailed analysis shows that the normalized superfluid density [Formula: see
      text], which is converted from [Formula: see text], can be well described by a
      multigap scenario, with nodes in one of the superconducting gaps, providing clear
      evidence for nodal superconductivity in Ta4Pd3Te16.

PMID- 29322946
TI  - The cover page.

PMID- 29322945
TI  - Observation of layered antiferromagnetism in self-assembled parallel NiSi
      nanowire arrays on Si(110) by spin-polarized scanning tunneling
      spectromicroscopy.
AB  - The layered antiferromagnetism of parallel nanowire (NW) arrays self-assembled on
      Si(110) have been observed at room temperature by direct imaging of both the
      topographies and magnetic domains using spin-polarized scanning tunneling
      microscopy/spectroscopy (SP-STM/STS). The topographic STM images reveal that the
      self-assembled unidirectional and parallel NiSi NWs grow into the Si(110)
      substrate along the [Formula: see text] direction (i.e. the endotaxial growth)
      and exhibit multiple-layer growth. The spatially-resolved SP-STS maps show that
      these parallel NiSi NWs of different heights produce two opposite magnetic
      domains, depending on the heights of either even or odd layers in the layer stack
      of the NiSi NWs. This layer-wise antiferromagnetic structure can be attributed to
      an antiferromagnetic interlayer exchange coupling between the adjacent layers in
      the multiple-layer NiSi NW with a B2 (CsCl-type) crystal structure. Such an
      endotaxial heterostructure of parallel magnetic NiSi NW arrays with a layered
      antiferromagnetic ordering in Si(110) provides a new and important perspective
      for the development of novel Si-based spintronic nanodevices.

PMID- 29322947
TI  - Neurosurgery as it was.

PMID- 29322948
TI  - Changing trends in surgery for suprasellar lesions.

PMID- 29322949
TI  - Evolution of concepts in the management of vestibular schwannomas: Lessons learnt
      from Prof B R Ramamurthi's article published in 1970.

PMID- 29322950
TI  - A medical-legal perspective on overlapping surgery.
AB  - In the U.S., there has recently been increased scrutiny on the appropriateness of
      surgeons performing overlapping cases and the potential for adverse consequences.
      This article describes the current literature on overlapping surgery and the
      ethics that guide behavior by performing a review of the PUBMED literature on
      overlapping surgery and analysis. Although the literature on overlapping surgery
      supports it as a safe practice, some public opinion runs contrary to the data,
      which is driving changes in policy. Surgeons should become familiar with the
      overlapping surgery policy in the hospital(s) in which they practice and be
      mindful of the potential consequences of performing overlapping surgeries.

PMID- 29322951
TI  - Cerebrospinal fluid shunts - How they work: The basics.

PMID- 29322952
TI  - Current status of dystonias including Meige's syndrome.

PMID- 29322953
TI  - Botulinum toxin in patients with Meige's syndrome.

PMID- 29322954
TI  - Management of intracranial arterial dissection.

PMID- 29322955
TI  - Endovascular management of vertebral artery dissecting aneurysms.

PMID- 29322956
TI  - Dissecting aneurysms of the vertebrobasilar system with non-traumatic
      subarachnoid haemorrhage: Therapeutic considerations.

PMID- 29322957
TI  - Is intraoperative lumbar subarachnoid drainage necessary for endoscopic endonasal
      pituitary surgery?

PMID- 29322958
TI  - The case for using lumbar drainage intraoperatively to help curb the number of
      iatrogenic CSF leaks.

PMID- 29322959
TI  - Neurological manifestations of renal disease.

PMID- 29322960
TI  - Neurology of renal disorders.

PMID- 29322961
TI  - Perioperative strokes following combined coronary artery bypass grafting and
      carotid endarterectomy: A nationwide perspective.
AB  - BACKGROUND: To assess the risk of perioperative stroke on in-hospital morbidity
      and mortality following combined coronary artery bypass grafting (CABG) and
      carotid endarterectomy (CEA). MATERIALS AND METHODS: Data from the National
      Inpatient Sample (NIS) database for all patients who underwent CABG with CEA were
      identified using ICD-9 codes. Combined procedures were identified as CEA and CABG
      procedures that happened on the same day. Various preoperative and perioperative
      risk factors and their association with in-hospital mortality and morbidity were
      studied. RESULTS: A total of 8457 patients underwent combined CABG and CEA from
      1999 to 2011. The average age of the patient population was 69.98 years. A total
      of 6.17% (n = 521) of the patients developed perioperative strokes following
      combined CABG and CEA. An in-hospital mortality of 4.96% and morbidity of 66.35%
      was observed in the patient cohort. Patients with perioperative strokes showed a
      mortality of 19% and a morbidity of 89.34%. Other notable risk factors for in
      hospital mortality and morbidity were heart failure, paralysis, renal failure,
      coagulopathy, weight loss and fluid and electrolyte disturbances, and
      postoperative myocardial infarction. CONCLUSION: A strong association was found
      to exist between perioperative stroke and in-hospital mortality and morbidity
      after combined CABG and CEA. CEA procedures are thought to mitigate the high
      stroke rate of 3-5% post-CABG, but our study found that combined procedures
      exhibit a similar stroke risk undercutting their effectiveness. Further
      investigative studies on combined CABG+CEA are needed to assess risk
      stratification for better patient selection and examine other preventative
      strategies to minimize the risk of ischemic strokes.

PMID- 29322962
TI  - Etiologic spectrum and prognosis in noncompressive acute transverse myelopathies:
      An experience of 80 patients at a tertiary care facility.
AB  - INTRODUCTION: We evaluated the spectrum of acquired demyelinating and
      inflammatory disorders in patients presenting with an acute transverse
      myelopathy. We also studied differences between an acute idiopathic transverse
      myelitis and myelitis resulting from other etiologies. MATERIALS AND METHODS:
      Eighty consecutive patients with acute transverse myelopathy were included. At
      inclusion, clinical profile, serum and cerebrospinal fluid parameters, brain and
      spinal cord magnetic resonance imaging, and visual evoked potentials were
      obtained. All patients were given methylprednisolone therapy. Patients were
      followed up for 6 months. Outcome was assessed using modified Barthel index. A
      modified Barthel index score of <=12 indicated a poor prognosis. RESULTS:
      Majority (n = 49; 61.25%) of patients had idiopathic acute transverse myelitis.
      Eleven cases had neuromyelitis optica spectrum disorders (8 had anti-aquaporin
      antibody positivity). Multiple sclerosis was diagnosed in 7 cases. Eight cases
      had infectious or parainfectious myelitis. Longitudinally extensive transverse
      myelitis was noted in 66 (82.5%) patients. Seventeen patients had abnormalities
      in the brain. Majority of patients improved following methylprednisolone therapy.
      On univariate analysis, delay in administering methylprednisolone therapy, poor
      modified Barthel index at discharge, and extensive cord involvement were
      associated with severe residual disability. On multivariate analysis, delayed
      initiation of methylprednisolone was identified as a poor prognostic factor.
      CONCLUSION: A variety of inflammatory, infective, demyelinating, and autoimmune
      disorders present with acute transverse myelopathy. Early institution of
      methylprednisolone reduces the disability in these patients.

PMID- 29322963
TI  - Botulinum toxin in Meige's syndrome: A video-based case series.
AB  - CONTEXT: Despite being the most common cause of cranial dystonia, Meige's
      syndrome remains a rare clinical entity. Characterized by blepharospasm and
      orofacial dystonia, patients suffering from Meige's syndrome benefit from the
      injection of botulinum toxin (BTX). AIMS: As the majority of the studies tend to
      discuss Meige's syndrome with blepharospasm patients, there is a paucity of case
      based studies dealing exclusively with this syndrome. Hence, we intended to
      characterize and define the evolution of this syndrome and objectively determine
      the response of the patients suffering from this entity to BTX therapy. MATERIALS
      AND METHODS: Eight patients with Meige's syndrome who had never been injected
      with BTX in the past were evaluated at our movement disorder clinic using a
      structured questionnaire. Videotaping of abnormal movements was done for 5
      minutes before the BTX injection and at a 1-month follow-up. All patients
      received electromyography-guided injection of BTX and the dosage was decided
      using clinical evaluation. Their demography, clinical features, and treatment
      response to BTX were analyzed using the "Burke-Fahn-Marsden dystonia rating
      scale" (BFMDRS) before injection and at a 1-month follow-up. RESULTS: The peak
      age of symptom onset was 46.4 years with a male: female ratio of 1:1. The average
      duration of symptoms was 6.43 years. Majority of the patients (6/8) manifested
      their disease with blepharospasm, including five patients who had clonic
      blepharospasm. Lingual dystonia (6/8) and pharyngeal involvement (4/8) were
      commonly noted. Sensory tricks were present in all, with placement of the fingers
      over eyelids being the commonest trick (7/8). The average BTX dose administered
      was 51.58 units, and the peak onset of relief was noted at 8.62 days after the
      injection. The duration of the effect lasted for 82.5 days on an average. Only
      one patient reported mild weakness of the muscles of mastication following BTX
      injection. The average BFMDRS improved from the preprocedural score of 25.06 to
      13.12 following the BTX injection. CONCLUSIONS: In this series exclusively
      dealing with Meige's syndrome patients, tongue involvement was found to be very
      common (6/8, 75%), and the response to the first dose of BTX treatment was found
      to be excellent without the occurrence of any major side effects.

PMID- 29322964
TI  - Natural history of a cohort of Duchenne muscular dystrophy children seen between
      1998 and 2014: An observational study from South India.
AB  - BACKGROUND: Duchenne muscular dystrophy (DMD) is the most common muscular
      dystrophy. There are no large studies describing its natural course from India.
      MATERIALS AND METHODS: Immunohistochemically/genetically confirmed DMD patients
      diagnosed between 1998 and 2014 were ambispectively included. The main aim was to
      study the natural course of motor milestones, i.e., age at onset of wheelchair
      status, bedbound state, and age at death, which were considered as primary
      outcome measures. We also correlated the DMD genotype with the motor milestones
      and other phenotypic features. RESULTS: A total of 500 DMD patients were included
      and 275 participated in the study. The mean age at symptom onset was 3.7 +/- 1.9
      years, mean age at presentation was 8.1 +/- 2.5 years, and mean duration of
      illness was 4.4 +/- 2.6 years. On following them over 15 years, 155 (56.4%) had
      attained at least one of the primary outcome measures. Wheelchair status was
      attained in 124 (45.1%) [mean age: 10.4 +/- 1.6 years] and bedbound state in 24
      (8.7%; mean age: 11.8 +/- 2.2 years) patients. Seven patients (2.6%) died during
      the follow-up period (mean age: 15.2 +/- 2.4 years). There was no significant
      impact of the genotypic or phenotypic features on the primary outcome.
      CONCLUSION: The pattern of major motor milestones (primary outcome measures) in
      this large cohort is comparable with that of the Western population despite
      variability in medical care. The genotypic pattern was also similar to other
      large studies, which suggests that DMD is a more homogeneous disorder with
      limited ethnic variability in its geno-phenotypic expression.

PMID- 29322965
TI  - Endovascular strategies for management of intradural vertebral artery dissecting
      aneurysms.
AB  - OBJECTIVE: Endovascular treatment of vertebral intradural dissecting aneurysms is
      complex and requires different strategies for each case. The current study aims
      to classify these aneurysms for an easy selection of optimal strategies for
      endovascular therapy. MATERIALS AND METHODS: This study is a retrospective
      evaluation of 10 patients harbouring a vertebral intradural dissecting aneurysm
      (including 6 female and 4 male patients). The clinical, procedural, and
      angiographic data were evaluated. RESULTS: Nine patients presented with acute
      subarachnoid hemorrhage and 1 with acute-onset headache. The aneurysms were
      classified into two types, depending on the developmental state of the
      contralateral vertebral artery: Dominant (A) and hypoplastic (B). Type A (n = 7)
      group was further divided into three subtypes on the basis of location of the
      aneurysm in relation to the posterior inferior cerebellar artery (PICA): aneurysm
      proximal to the PICA, Type I (n = 3); involving the PICA, Type II (n = 2); and,
      distal to the PICA, Type III (n = 2). Internal trapping was done for 4 patients
      in this group, 2 patients with aneurysm involving the PICA underwent proximal
      occlusion and 1 patient underwent stent-assisted coiling since he refused to
      undergo vertebral artery sacrifice. B Type patients (n = 3) were treated with
      reconstructive endovascular management. No symptomatic complication was seen in
      the patients with trapping. Antiplatelet medication-related complication was seen
      in 2 patients who underwent stent-assisted coiling. Clinical outcome at the time
      of discharge was good [modified Rankin score (mRS) 0-2] in 8 and poor (mRs >2) in
      2 patients. At follow-up visit, one patient had developed severe cognitive
      impairment but was independent in activities of daily living. CONCLUSION: The
      classification of vertebral artery aneurysms based on their location and on the
      status of the contralateral vertebral artery appears to be an effective method
      for the selection of safe and appropriate endovascular therapy.

PMID- 29322966
TI  - The influence of adjunctive caudal epidural steroid injection on the therapeutic
      effect of transforaminal epidural steroid injection.
AB  - BACKGROUND: Epidural steroid injection is widely used to treat the short and long
      term symptoms of low back and radicular pain. To the best of our knowledge, the
      influence of transforaminal epidural steroid injection (TFSI) combined with
      caudal epidural steroid injection (CESI) on pain intensity, patient satisfaction,
      and quality of life in lumbar radiculopathy has not been examined. AIM: To
      evaluate the short and long-term efficacy of TFSI, and TFSI combined with CESI
      (TFSI + CESI) in patients with lumbar radiculopathy. MATERIALS AND METHODS: We
      retrospectively examined the records of 104 patients with lumbar radicular pain
      and L4/5 and/or L5/S1 intervertebral disc disease who underwent TFSI or TFSI +
      CESI. We compared the pain intensity using a Visual Numeric Scale (VNS), North
      American Spine Society (NASS) pain satisfaction index, and EuroQol five
      dimensions (EQ-5D) quality of life scores before intervention, and after 1, 6 and
      12 months. RESULTS: In the TFSI group, the mean pre-treatment VNS score was 9.2,
      which improved to 4.9 after 1 month and to 7.2 after 12 months. In the TFSI +
      CESI group, the mean pre-treatment VNS score was 9.4, which improved to 2.6 and
      4.6 after 1 and 12 months, respectively. Improvement in the VNS scores was
      significantly higher in the TFSI + CESI group (P < 0.0001 for each). Mean EQ-5D
      quality of life index in the TFSI group improved from 0.59 in the pre-treatment
      phase to 0.76 after 12 months of intervention, while it improved from 0.62 in the
      pre-treatment phase to 0.84 at 12 months of intervention in the TFSI + CESI
      group. The EQ-5D scores were significantly better in the TFSI + CESI group at 1,
      6, and 12 months after the procedure (P = 0.004, 0.036, and 0.042, for 1, 6, and
      12 months, respectively). The NASS scores were significantly better in the TFSI +
      CESI group at 6 and 12 months after the intervention (P = 0.025 and 0.001 for 6
      months and 12 months, respectively). CONCLUSION: In patients with lower lumbar
      radiculopathy, a combined TFSI + CESI technique offers superior short and long
      term pain relief, quality of life, and long-term patient satisfaction, than when
      TFSI is performed alone.

PMID- 29322967
TI  - Alternative bibliometrics from the web of knowledge surpasses the impact factor
      in a 2-year ahead annual citation calculation: Linear mixed-design models'
      analysis of neuroscience journals.
AB  - CONTEXT: The decision about which journal to choose for the publication of
      research deserves further investigation. AIMS: In this study, we evaluate the
      predictive ability of seven bibliometrics in the Web of Knowledge to calculate
      total cites over a 7-year period in neuroscience journals. SETTINGS AND DESIGN:
      Coincidental bibliometrics appearing during 2007, 2008, 2009, 2010, and 2011,
      along with their corresponding cites in 2009, 2010, 2011, 2012, and 2013, were
      recorded from the journal citation reports (JCR) Science Edition. This was a
      retrospective study. MATERIALS AND METHODS: This was a bibliographic research
      using data from the Web of Knowledge in the neuroscience category. STATISTICAL
      ANALYSIS USED: A linear-mixed effects design using random slopes and intercepts
      was performed on 275 journals in the neuroscience category. RESULTS: We found
      that Eigenfactor score, cited half-life, immediacy index, and number of articles
      are significant predictors of 2-year-ahead total cites (P <= 0.010 for all
      variables). The impact factor, 5-year impact factor, and article influence score
      were not significant predictors; the global effect size was significant (R2=
      0.999; P < 0.001) with a total variance of 99.9%. CONCLUSIONS: An integrative
      model using a set of several metrics could represent a new standard to assess the
      influence and importance of scientific journals, and may simultaneously help
      researchers to rank journals in their decision-making during the manuscript
      submission phase.

PMID- 29322968
TI  - Treatment strategies for traumatic cervico-cranial pseudoaneurysms: A single
      institution experience.
AB  - AIM: Limited clinical and angiographic data exists for patients with traumatic
      cervico-cerebral pseudoaneurysms. In this paper, we present our limited
      experience with various management strategies for traumatic cervico-cranial
      pseudoaneurysms. MATERIALS AND METHODS: We retrospectively analyzed 37
      consecutive cases of traumatic pseudoaneurysms involving the cervico-cranial or
      the cerebral arteries diagnosed at our center from September 2009 to December
      2014. The demographic data, etiology, clinical presentation, lesion location,
      treatment modality, and follow-up outcomes of these patients were reviewed. Among
      these 37 patients, 5 patients were treated by surgery, while 29 patients were
      treated by the endovascular approach and 3 received conservative treatment.
      RESULTS: During the study period, 42 pseudoaneurysms were identified in 37
      patients with a history of head or neck injury. Five patients underwent surgical
      exploration of the lesion with an uneventful postoperative course. Twenty-nine
      patients were treated by endovascular interventions with various embolization
      materials including coils, stents, detachable balloons, liquid embolic agents,
      and a combination of these agents. The angiographic follow-up imaging
      demonstrated complete exclusion of the aneurysm from the circulation with the
      patient being free from any additional neurological deficits. CONCLUSION: Proper
      selection of an appropriate approach is essential to address the management of
      traumatic cervico-cerebral pseudoaneurysms. The treatment of traumatic cervico
      cerebral pseudoaneurysms should be selected according to the location and the
      clinical features of the pseudoaneurysms. The endovascular treatment is a safe
      and effective modality and should be the first-line choice for treatment of
      traumatic pseudoaneurysms.

PMID- 29322969
TI  - Pseudoaneurysms of the craniocervical region.

PMID- 29322970
TI  - Minimally invasive transforaminal lumbar interbody fusion using bone cement
      augmented pedicle screws for lumbar spondylolisthesis in patients with
      osteoporosis. Case series and review of literature.
AB  - BACKGROUND: Instrumentation in patients with osteoporosis is challenging. Bone
      cement-augmented fenestrated pedicle screw fixation is a new procedure for
      fixation in the osteoporotic bone; and, applying minimally invasive techniques to
      the above is a challenging and novel concept. AIMS: To evaluate the clinical and
      radiological outcome of minimally invasive spine surgery transforaminal lumbar
      interbody fusion (MIS-TLIF) in patients with spondylolisthesis and poor bone
      quality, performed with rigid instrumentation using bone cement
      [poly(methylmethacrylate)]-augmented fenestrated pedicle screws. SETTINGS AND
      DESIGN: Prospective, observational, single-center study. STATISTICAL ANALYSIS
      USED: Wilcoxon nonparametric test for paired samples with a level of significance
      of 0.05. METHODS: A clinical series of 25 patients with lumbar spondylolisthesis
      and osteoporosis who underwent minimally invasive TLIF with bone cement-augmented
      pedicle screws were included in the study. Clinical outcome and the function were
      assessed using the visual analog scale (VAS) score for pain and the Oswestry
      Disability Index (ODI). Perioperative, postoperative, and long-term complications
      were monitored with a mean follow-up of 18 months. RESULTS: A total of 25 (20
      female and 5 male) patients were included in the study with an average age of
      61.05 years. The major symptom was low back pain with radiating pain to lower
      limbs. The average T-score was -3.0. All the patients were followed clinically
      and radiologically. There was a statistically significant improvement in the VAS
      scores and ODI scores postoperatively. No events of cement extravasation,
      radiological loosening, or pulling out of screws were observed. CONCLUSIONS:
      Fenestrated pedicle screw fixation with bone cement augmentation in patients with
      osteoporosis is a well-established alternative to increase the pullout strength
      of screws placed in the osteoporotic bone. Applying the concept of minimally
      invasive surgery to this procedure makes it a more complete solution for
      instrumentation in osteoporotic spine. Our series is the largest in literature on
      spondylolisthesis and confirms the feasibility and safety of this procedure in
      treating spondylolisthesis in the aging population.

PMID- 29322971
TI  - Osteoporotic lumbar spine - Principles of pedicle screw fixation and interbody
      fusion.

PMID- 29322972
TI  - A randomized controlled trial to determine the role of intraoperative lumbar
      cerebrospinal fluid drainage in patients undergoing endoscopic transsphenoidal
      surgery for pituitary adenomas.
AB  - BACKGROUND: Intraoperative cerebrospinal fluid (CSF) leaks are a frequent cause
      of morbidity in patients undergoing transsphenoidal surgery. This prospective
      study was performed to examine the impact of intraoperative lumbar subarachnoid
      drainage (LSAD) on the incidence of this complication and on the extent of
      resection in patients undergoing endoscopic transsphenoidal surgery for pituitary
      adenomas. MATERIALS AND METHODS: This prospective study was conducted in a single
      large academic medical center. All patients with pituitary adenomas who had not
      undergone prior transsphenoidal surgery were eligible for inclusion in the study.
      Patients were randomly assigned to undergo transsphenoidal surgery with
      intraoperative lumbar drain insertion (LSAD group) or no lumbar drain insertion
      (no LSAD group). An otolaryngologist independently determined the occurrence of
      an intraoperative CSF leak. Extent of tumor resection was determined by
      volumetric analysis of postoperative magnetic resonance images in patients with
      nonfunctional tumors or functional adenomas with a large suprasellar component.
      RESULTS: Sixty patients were eligible for inclusion, of which 30 were assigned to
      the LSAD group and 30 to the no LSAD group. There were no statistically
      significant differences in patient demographics, tumor pathology, or radiology
      between the two groups. The LSAD catheter was successfully inserted in all
      patients in the LSAD group. Intraoperative CSF drainage significantly reduced the
      incidence of CSF leak from 46.7% in the no LSAD group to 3.3% in the LSAD group
      (P < 0.001). However, there were no statistically significant differences in the
      incidence of postoperative CSF rhinorrhea between the two groups. There were no
      major catheter-related complications. There was no statistically significant
      difference in the extent of resection between the two groups. CONCLUSIONS:
      Controlled intraoperative CSF drainage significantly reduces the incidence of
      intraoperative CSF leakage in patients undergoing endoscopic transsphenoidal
      surgery for pituitary adenomas.

PMID- 29322974
TI  - Facial schwannomas: Diagnosis and surgical perspectives.

PMID- 29322973
TI  - Facial nerve schwannomas: A case series with an analysis of imaging findings.
AB  - Facial nerve schwannomas (FNSs) are rare benign tumors arising from the Schwann
      cells of the sheath of the facial nerve. These tumors may arise anywhere along
      the course of the facial nerve. Owing to their rarity and nonspecific clinical
      and radiological presentations, the preoperative diagnosis of FNSs is exceedingly
      difficult. In this study, we present four cases of histopathologically proven
      extratemporal schwannomas and a solitary case of intratemporal schwannoma. The
      purpose of this study was mainly focused on analyzing the imaging findings of
      extratemporal and intratemporal schwannomas in an effort to better characterize
      these lesions preoperatively. An early diagnosis of FNSs is helpful for the
      management and rehabilitation of these cases.

PMID- 29322975
TI  - Atlantoaxial instability associated with pan cervical vertebral fusion: Report on
      management of 4 cases.
AB  - We report a series of four patients aged 4, 5, 14, and 27 years (1 male and 3
      female patients) with severe shortening of the neck and torticollis since early
      childhood who presented with complaint of pain in the nape of neck as the primary
      symptom. All four patients had relatively well preserved neurological functions.
      One patient had vertical mobile and reducible atlantoaxial dislocation, and 3
      patients had anteroposterior mobile and reducible dislocation. There was
      assimilation of atlas in 1 patient. The arch of atlas was bifid in 3 patients.
      Two patients underwent atlantoaxial fixation. Both the patients were relieved of
      neck pain after their surgery. The potential surgical difficulties due to the
      presence of severe shortening of neck height and marginal presenting symptoms
      favored conservative observation in the other 2 patients. Follow-up ranged from 6
      to 84 months. All patients are functionally and socially active.

PMID- 29322976
TI  - "Fusing the appropriate" in complex craniovertebral junction anomalies.

PMID- 29322977
TI  - The chicken or the egg - Pancervical fusion with atlantoaxial dislocation.

PMID- 29322978
TI  - Chromosomal aberrations in chordoid meningioma - An analysis.
AB  - INTRODUCTION: Chordoid meningiomas (CMs) are a rare subgroup of tumors,
      accounting for approximately 0.5% of all meningiomas. These tumors correspond to
      World Health Organization (WHO) Grade II lesions and behave aggressively, with an
      increased likelihood of recurrence. There are only two studies that have
      described the genetic alterations in CMs. While a majority of meningiomas are
      known to have deletion at many chromosomal loci such as 22q, 18p, 14q, and 1p,
      which are found to be associated with initiation, progression, and malignancy of
      these tumors, these have not yet been studied in CMs. Thus, our aim was to
      evaluate the status of these four chromosomal aberrations in CMs and correlate
      the findings with the clinical outcome of patients. MATERIALS AND METHODS: A
      total of 15 cases of CM operated over a period of 12 years from 2001 to 2013 were
      analyzed. The archival paraffin blocks were retrieved and sections were subjected
      to locus-specific fluorescent in situ hybridization (FISH) using 22q12.2,
      18p11.3, 14q32.2, and 1p32.3 probes. Immunohistochemistry (IHC) was done on all
      cases using MIB-1, vimentin, glial fibrillary acidic protein (GFAP), and
      epithelial membrane antigen (EMA) antibodies. RESULTS: All cases had
      characteristic features of CM, and were positive for EMA and vimentin and
      negative for GFAP. The mean labeling index for MIB-1 was 2.7 +/- 0.8%. Of the 15
      cases, 5 cases showed recurrence with a median follow-up period of 28 months.
      Patients who underwent Simpson's grade I excision did not show any relapse of the
      tumor. Of the 5 recurrent cases, 4 had complete deletion of all four chromosomal
      loci. Among the 10 nonrecurrent cases, 9 (90%) showed either partial deletion or
      an intact status. CONCLUSIONS: This is the first study to evaluate the combined
      chromosomal status of 22q, 18p, 14q, and 1p in CMs. Our study shows that there
      was a higher propensity of recurrence in tumors, even with complete excision,
      with complete deletion in all four chromosomal loci.

PMID- 29322979
TI  - Meningiomas: A continuum of progress in risk-stratification.

PMID- 29322980
TI  - Neurology of renal disorders.
AB  - Chronic kidney disease (CKD) is a critical and rapidly growing global health
      problem. Neurological complications occur in almost all patients with severe CKD,
      potentially affecting all levels of the nervous system, from the central nervous
      system (CNS) through to the peripheral nervous system (PNS). Patients with CKD
      exhibit a high incidence of symptomatic and occult cerebrovascular diseases,
      associated tremendously high levels of inflammatory factors and homocysteine, as
      well as anemia, hypertension, and diabetes. As these risk factors overshadow
      aging and nonvascular factors, CKD patients represent a potential model of
      accelerated vascular cognitive impairment. In this article, the disease-related
      and treatment-related neurological complications of renal disorders will be
      reviewed.

PMID- 29322981
TI  - Expansile manubriotomy for ventral cervicothoracic junction disease.
AB  - Cervicothoracic junction can be approached anteriorly, anterolaterally,
      posterolaterally, and posteriorly. The anterior approaches in this region best
      address the ventral vertebral body disease but may cause significant morbidity.
      Twelve patients with their disease process located ventral to the spinal cord in
      the cervicothoracic junction underwent expansile manubriotomy and corpectomy.
      Eleven patients underwent fusion. One patient underwent an oblique corpectomy.
      All patients had their disease process from T1 to T3 vertebral levels. After
      dissection, the manubrium was cut open in the midline until the sternal notch.
      Further manubrial cut was extended laterally to just below the second rib. A self
      retaining retractor was placed and opened. This gave an additional exposure of 10
      cm from the midline towards the right side. It also opened the thoracic inlet.
      The superior mediastinum was dissected. Brachiocephalic vessels were looped down
      and a plane was made between the carotid artery laterally, and the trachea and
      esophagus medially. The prevertebral fascia was reached and opened to access the
      vertebral body. The procedure could be carried out successfully in all the
      patients. A patient with uncontrolled diabetes mellitus and end-stage renal
      disease with pyogenic epidural abscess succumbed to her illness after 3 weeks.
      Expansile manubriotomy is technically feasible, less invasive, and least morbid
      of all the anterior approaches for accessing the anteriorly located disease
      process above the T4 vertebral level.

PMID- 29322982
TI  - Expansile manubriotomy versus standard approach for accessing ventral
      cervicothoracic junction disease: Methods to improve the decision-making process.

PMID- 29322985
TI  - PGIMER, Chandigarh: A temple of holistic Neurology.
AB  - History helps us to become better students, judge wisely, understand change, and
      most importantly, it tells us who we are. It helps us to understand what
      happened, why it happened and what its ramifications are. Winston Churchill once
      said: "Study history, study history. In history lie all the secrets of
      statecraft." Here, we take this opportunity to pay our gratitude to our esteemed
      teachers who worked relentlessly for uplifting of the department of Neurology,
      PGIMER, Chandigarh; and, narrate chronicles of all those people who made this
      department reach the heights where it stands today.

PMID- 29322984
TI  - A device for three-dimensional quantitative assessment and alignment of C1-2
      vertebrae during posterior distraction and fusion technique for atlantoaxial
      dislocation and/or basilar invagination.
AB  - The most common type of congenital C1-2 dislocation is a combined type in which
      atlanto-axial dislocation (AAD) and basilar invagination (BI) are often
      associated with a rotational dislocation and coronal tilt. An optimal surgical
      treatment involves reduction of AAD and BI with simultaneous correction of the
      rotation and coronal tilt to achieve an optimal cervical canal decompression,
      sagittal and coronal realignment and bony fusion. The most acceptable technique
      to facilitate this correction is the C1-C2 distraction technique, which is
      accomplished by the manual joint manipulation. In this study, the authors
      describe an instrument that accomplishes distraction of the C12 joint space along
      with its quantitative assessment, permits the easy installation of a joint spacer
      without damage to the articular surfaces, brings about reduction of AAD and BI,
      while simultaneously also helping in the correction of the coexisting coronal
      tilt and rotational dislocation. This distractor not only achieves a multi-planar
      three-dimensional correction of the displacements at the C1-2 vertebral level,
      but may be used for the quantitative assessment of the correction and is
      compatible with the related surgical instruments of all standard companies
      utilized in this operative procedure.

PMID- 29322986
TI  - A summary of some of the recently published, seminal papers in neurosciences.

PMID- 29322983
TI  - Auditory P300 event-related potential: Normative data in the Indian population.
AB  - OBJECTIVE: To generate the normative data of auditory P300 event-related
      potential for various age groups in the Indian population. MATERIALS AND METHODS:
      Auditory P300 event-related potentials, using the oddball paradigm, of healthy
      control participants in studies carried out at our institute were included to
      generate normative data in the age range of 10-50 years. The amplitude and
      latency of P300 for Fz, Cz, and Pz were selected for analysis. RESULTS: For P300
      amplitude, overall multivariate analysis of variance (MANOVA) was significant
      [Pillai's Trace F (9/453) = 3.46, P < 0.001]. Follow-up ANOVA showed significant
      difference across age groups at Fz, Cz, and Pz. For P300 latency, there was a
      trend towards significance for overall MANOVA [Pillai's Trace F (9/453) = 1.68, P
      = 0.09]. Follow-up ANOVA showed a trend towards significant difference across age
      groups at Fz only. CONCLUSION: Our study generated a P300 amplitude and frequency
      normative database at Fz, Cz, and Pz, which will serve as a reference for future
      studies attempting to define P300 abnormalities in various psychiatric disorders
      in Indian population.

PMID- 29322987
TI  - Complications related to sitting position during Pediatric Neurosurgery: An
      institutional experience and review of literature.
AB  - BACKGROUND: Sitting position is preferred during posterior fossa surgeries as it
      provides better anatomical orientation and a clear surgical field. However, its
      use has been declining due to its propensity to cause life-threatening
      complications. This study was carried out to analyze the perioperative
      complications and postoperative course of children who underwent neurosurgery in
      sitting position. MATERIALS AND METHODS: Medical records of 97 children (<18
      years) who underwent neurosurgery in sitting position over a period of 12 years,
      were retrospectively analyzed. Data pertaining to the perioperative course such
      as demographics, hemodynamic changes, various complications, duration of
      intensive care unit (ICU) and hospital stay, and neurological status at discharge
      were recorded. Statistical analysis was done by chi-square and Mann-Whitney test,
      and a P value <0.05 was considered as significant. RESULTS: The median age of
      these children was 12 (3-18) years. Hemodynamic instability was observed in 12
      (12.3%) children. A total of 38 episodes of venous air embolism (VAE) were
      encountered in 21 (21.6%) children; nine experienced multiple episodes. VAE was
      associated with hypotension in five (23.8%) and desaturation in four (19.1%)
      children. Six children presented with postoperative tension pneumocephalus; three
      were managed with twist drill burr-hole evacuation. Brainstem handling was the
      most common indication (42.5%) for the requirement of elective postoperative
      ventilation. The duration of ICU and hospital stays were comparable among the
      children who experienced VAE and those who did not (P > 0.05). Neurological
      status at discharge was also comparable between these two groups (P = 0.83).
      CONCLUSIONS: This study observed a lesser incidence of VAE and associated
      complications. Tension pneumocephalus was managed successfully without any
      adverse outcome. Hence, it is believed that with meticulous anesthetic and
      surgical techniques, sitting position can safely be practiced in children
      undergoing neurosurgery.

PMID- 29322988
TI  - The sitting position for Neurosurgery: A bane or a boon.

PMID- 29322989
TI  - Association of hemolysis, elevated liver enzymes, low platelets syndrome with
      posterior reversible encephalopathy and intracranial hypotension.

PMID- 29322990
TI  - Carotid stump syndrome treated with endovascular coiling: A rare cause of stroke
      in young patients.

PMID- 29322991
TI  - Sporadic spinocerebellar ataxia, type 5: First report from India.

PMID- 29322992
TI  - CARASIL, a rare genetic cause of stroke in the young.

PMID- 29322993
TI  - Sertraline-induced reversible myopathy with rhabdomyolysis and trismus.

PMID- 29322994
TI  - Ictal bradycardia: A missed etiology for intraoperative bradycardia.

PMID- 29322995
TI  - Familial amyloid polyneuropathy due to p.ALA140 SER mutation.

PMID- 29322996
TI  - Disseminated cysticercosis presenting as status epilepticus, rhabdomyolysis, and
      acute kidney injury: An unreported complication.

PMID- 29322997
TI  - Lumber nerve root cavernous angioma.

PMID- 29322998
TI  - Primary sphenoid wing meningioma in contiguity with a glioblastoma.

PMID- 29322999
TI  - Sacral Ewing's tumor: Use of neoadjuvant chemotherapy for preoperative
      cytoreduction of the tumor.

PMID- 29323000
TI  - Primary diffuse leptomeningeal gliomatosis: A coveted diagnosis we think of less.

PMID- 29323001
TI  - Dirofilariasis mimicking an osteoma.

PMID- 29323002
TI  - Trans-third ventricular approach to basilar top aneurysm.

PMID- 29323003
TI  - Primary lymphoma of the radial nerve presenting as nerve sheath tumor.

PMID- 29323004
TI  - Middle meningeal arteriovenous fistula causing unilateral proptosis.

PMID- 29323005
TI  - Nasu-Hakola Disease.

PMID- 29323006
TI  - Spastic paraparesis with basal ganglia changes: Infantile neuroaxonal dystrophy.

PMID- 29323007
TI  - Triad of gloom in a girl child: Aicardi syndrome.

PMID- 29323008
TI  - Multiple extraneural metastases from a benign intracranial meningioma.

PMID- 29323009
TI  - Reversible symptoms present in a patient with Balo's concentric sclerosis.

PMID- 29323010
TI  - Revisiting a historical phenomenon: Myodil droplets in the subarachnoid space.

PMID- 29323011
TI  - Multiple cranial nerve enhancement as a rare presentation of secondary brain
      lymphoma.

PMID- 29323012
TI  - Senior citizenship in neurosurgery.

PMID- 29323014
TI  - India and its potential for neuroinformatics.

PMID- 29323015
TI  - Anesthetic considerations for intraoperative neurophysiological monitoring in
      patients undergoing scoliosis surgery.

PMID- 29323016
TI  - Magnesium: Hope for prehospital care in intracranial hemorrhage.

PMID- 29323013
TI  - The Indo-US Collaborative Stroke Registry and infrastructure development project.

PMID- 29323017
TI  - Authors' Reply: Magnesium supplementation in intracerebral hematoma: The hope and
      the hype!

PMID- 29323018
TI  - Arterial spin labeling.

PMID- 29323019
TI  - Authors' Reply: Arterial spin labeling: Clarifying the apparent contradiction.

PMID- 29323020
TI  - Author's Reply: Arterial spin labeling.

PMID- 29323021
TI  - Subgaleoatrial or subgaleopleural shunt?

PMID- 29323022
TI  - Authors' Reply: In defence of subgaleoatrial shunt!

PMID- 29323023
TI  - Visual outcome following microscopic transsphenoidal surgery for pituitary
      adenomas: A few concerns.

PMID- 29323024
TI  - Authors' Reply: How long can the optic nerve defy compression?

PMID- 29323025
TI  - Non-invasive brain stimulation to promote motor and functional recovery following
      spinal cord injury.
AB  - We conducted a systematic review of studies using non-invasive brain stimulation
      (NIBS: repetitive transcranial magnetic stimulation (rTMS) and transcranial
      direct current stimulation (tDCS)) as a research and clinical tool aimed at
      improving motor and functional recovery or spasticity in patients following
      spinal cord injury (SCI) under the assumption that if the residual corticospinal
      circuits could be stimulated appropriately, the changes might be accompanied by
      functional recovery or an improvement in spasticity. This review summarizes the
      literature on the changes induced by NIBS in the motor and functional recovery
      and spasticity control of the upper and lower extremities following SCI.

PMID- 29323026
TI  - The contribution of oligodendrocytes and oligodendrocyte progenitor cells to
      central nervous system repair in multiple sclerosis: perspectives for
      remyelination therapeutic strategies.
AB  - Oligodencrocytes (OLs) are the main glial cells of the central nervous system
      involved in myelination of axons. In multiple sclerosis (MS), there is an
      imbalance between demyelination and remyelination processes, the last one
      performed by oligodendrocyte progenitor cells (OPCs) and OLs, resulting into a
      permanent demyelination, axonal damage and neuronal loss. In MS lesions,
      astrocytes and microglias play an important part in permeabilization of blood
      brain barrier and initiation of OPCs proliferation. Migration and differentiation
      of OPCs are influenced by various factors and the process is finalized by
      insufficient acummulation of OLs into the MS lesion. In relation to all these
      processes, the author will discuss the potential targets for remyelination
      strategies.

PMID- 29323028
TI  - Surgical reconstruction of spinal cord circuit provides functional return in
      humans.
AB  - This mini review describes the current surgical strategy for restoring function
      after traumatic spinal nerve root avulsion in brachial or lumbosacral plexus
      injury in man. As this lesion is a spinal cord or central nervous injury
      functional return depends on spinal cord nerve cell growth within the central
      nervous system. Basic science, clinical research and human application has
      demonstrated good and useful motor function after ventral root avulsion followed
      by spinal cord reimplantation. Recently, sensory return could be demonstrated
      following spinal cord surgery bypassing the injured primary sensory neuron.
      Experimental data showed that most of the recovery depended on new growth
      reinnervating peripheral receptors. Restored sensory function and the return of
      spinal reflex was demonstrated by electrophysiology and functional magnetic
      resonance imaging of human cortex. This spinal cord surgery is a unique treatment
      of central nervous system injury resulting in useful functional return. Further
      improvements will not depend on surgical improvements. Adjuvant therapy aiming at
      ameliorating the activity in retinoic acid elements in dorsal root ganglion
      neurons could be a new therapeutic avenue in restoring spinal cord circuits after
      nerve root avulsion injury.

PMID- 29323027
TI  - MicroRNAs in Parkinson's disease and emerging therapeutic targets.
AB  - Parkinson's disease (PD) is the second most common age-related neurodegenerative
      disorder, with the clinical main symptoms caused by a loss of dopaminergic
      neurons in the substantia nigra, corpus striatum and brain cortex. Over 90% of
      patients with PD have sporadic PD and occur in people with no known family
      history of the disorder. Currently there is no cure for PD. Treatment with
      medications to increase dopamine relieves the symptoms but does not slow down or
      reverse the damage to neurons in the brain. Increasing evidence points to
      inflammation as a chief mediator of PD with inflammatory response mechanisms,
      involving microglia and leukocytes, activated following loss of dopaminergic
      neurons. Oxidative stress is also recognized as one of the main causes of PD, and
      excessive reactive oxygen species (ROS) and reactive nitrogen species can lead to
      dopaminergic neuron vulnerability and eventual death. MicroRNAs control a range
      of physiological and pathological functions, and may serve as potential targets
      for intervention against PD to mitigate damage to the brain. Several studies have
      demonstrated that microRNAs can regulate oxidative stress and prevent ROS
      mediated damage to dopaminergic neurons, suggesting that specific microRNAs may
      be putative targets for novel therapeutic strategies in PD. Recent human and
      animal studies have identified a large number of dysregulated microRNAs in PD
      brain tissue samples, many of which were downregulated. The dysregulated
      microRNAs affect downstream targets such as SNCA, PARK2, LRRK2, TNFSF13B, LTA,
      SLC5A3, PSMB2, GSR, GBA, LAMP-2A, HSC. Apart from one study, none of the studies
      reviewed had used agomirs or antagomirs to reverse the levels of downregulated or
      upregulated microRNAs, respectively, in mouse models of PD or with isolated human
      or mouse dopaminergic cells. Further large-scale studies of brain tissue samples
      collected with short postmortem interval from human PD patients are warranted to
      provide more information on the microRNA profiles in different brain regions and
      to test for gender differences.

PMID- 29323030
TI  - Formin' bridges between microtubules and actin filaments in axonal growth cones.

PMID- 29323031
TI  - Advanced diffusion-weighted magnetic resonance imaging in the evaluation of white
      matter axons in patients with idiopathic normal pressure hydrocephalus.

PMID- 29323029
TI  - Environmental cues determine the fate of astrocytes after spinal cord injury.
AB  - Reactive astrogliosis occurs after central nervous system (CNS) injuries whereby
      resident astrocytes form rapid responses along a graded continuum. Following CNS
      lesions, naive astrocytes are converted into reactive astrocytes and eventually
      into scar-forming astrocytes that block axon regeneration and neural repair. It
      has been known for decades that scarring development and its related
      extracellular matrix molecules interfere with regeneration of injured axons after
      CNS injury, but the cellular and molecular mechanisms for controlling astrocytic
      scar formation and maintenance are not well known. Recent use of various genetic
      tools has made tremendous progress in better understanding genesis of reactive
      astrogliosis. Especially, the latest experiments demonstrate environment
      dependent plasticity of reactive astrogliosis because reactive astrocytes
      isolated from injured spinal cord form scarring astrocytes when transplanted into
      injured spinal cord, but revert in retrograde to naive astrocytes when
      transplanted into naive spinal cord. The interactions between upregulated type I
      collagen and its receptor integrin beta1 and the N-cadherin-mediated cell
      adhesion appear to play major roles for local astrogliosis around the lesion.
      This review centers on the environment-dependent plasticity of reactive
      astrogliosis after spinal cord injury and its potential as a therapeutic target.

PMID- 29323032
TI  - Conductive polymer scaffolds to improve neural recovery.

PMID- 29323033
TI  - Coenzyme Q10 as a therapeutic candidate for treating inherited photoreceptor
      degeneration.

PMID- 29323034
TI  - Implications of periostin in the development of subarachnoid hemorrhage-induced
      brain injuries.

PMID- 29323035
TI  - Intentional and unintentional impacts of anaesthesia: insights from experiments
      in pain and injury.

PMID- 29323036
TI  - The Drosophila adult neuromuscular junction as a model for unravelling amyloid
      peptide influence on synapse dynamics.

PMID- 29323037
TI  - Bone marrow-derived mesenchymal stem cells ameliorate sodium nitrite-induced
      hypoxic brain injury in a rat model.
AB  - Sodium nitrite (NaNO2) is an inorganic salt used broadly in chemical industry.
      NaNO2 is highly reactive with hemoglobin causing hypoxia. Mesenchymal stem cells
      (MSCs) are capable of differentiating into a variety of tissue specific cells and
      MSC therapy is a potential method for improving brain functions. This work aims
      to investigate the possible therapeutic role of bone marrow-derived MSCs against
      NaNO2 induced hypoxic brain injury. Rats were divided into control group (treated
      for 3 or 6 weeks), hypoxic (HP) group (subcutaneous injection of 35 mg/kg NaNO2
      for 3 weeks to induce hypoxic brain injury), HP recovery groups N-2wR and N-3wR
      (treated with the same dose of NaNO2 for 2 and 3 weeks respectively, followed by
      4-week or 3-week self-recovery respectively), and MSCs treated groups N-2wSC and
      N-3wSC (treated with the same dose of NaNO2 for 2 and 3 weeks respectively,
      followed by one injection of 2 * 106 MSCs via the tail vein in combination with 4
      week self-recovery or intravenous injection of NaNO2 for 1 week in combination
      with 3 week self-recovery). The levels of neurotransmitters (norepinephrine,
      dopamine, serotonin), energy substances (adenosine monophosphate, adenosine
      diphosphate, adenosine triphosphate), and oxidative stress markers
      (malondialdehyde, nitric oxide, 8-hydroxy-2'-deoxyguanosine, glutathione reduced
      form, and oxidized glutathione) in the frontal cortex and midbrain were measured
      using high performance liquid chromatography. At the same time, hematoxylin-eosin
      staining was performed to observe the pathological change of the injured brain
      tissue. Compared with HP group, pathological change of brain tissue was milder,
      the levels of malondialdehyde, nitric oxide, oxidized glutathione, 8-hydroxy-2'
      deoxyguanosine, norepinephrine, serotonin, glutathione reduced form, and
      adenosine triphosphate in the frontal cortex and midbrain were significantly
      decreased, and glutathione reduced form/oxidized glutathione and adenosine
      monophosphate/adenosine triphosphate ratio were significantly increased in the
      MSCs treated groups. These findings suggest that bone marrow-derived MSCs exhibit
      neuroprotective effects against NaNO2-induced hypoxic brain injury through
      exerting anti-oxidative effects and providing energy to the brain.

PMID- 29323038
TI  - Electroacupuncture improves neurovascular unit reconstruction by promoting
      collateral circulation and angiogenesis.
AB  - Acupuncture at Shuigou (GV26) shows good clinical efficacy for treating stroke,
      but its mechanism remains poorly understood. In this study, a cerebral infarction
      model of ischemia/reperfusion injury received electroacupuncture at GV26 (15 Hz
      and 1 mA, continuous wave [biphasic pulses], for 5 minutes). Electroacupuncture
      effectively promoted regional cerebral blood flow on the infarct and non-infarct
      sides, increased infarct lesions, lectin, and number of blood vessels,
      upregulated von Willebrand factor and cell proliferation marker Ki67 expression,
      and diminished neurological severity score. These findings confirm that
      electroacupuncture at GV26 promotes establishment of collateral circulation and
      angiogenesis, and improves neurological function.

PMID- 29323039
TI  - Neuronal injury and tumor necrosis factor-alpha immunoreactivity in the rat
      hippocampus in the early period of asphyxia-induced cardiac arrest under
      normothermia.
AB  - Low survival rate occurs in patients who initially experience a spontaneous
      return of circulation after cardiac arrest (CA). In this study, we induced
      asphyxial CA in adult male Sprague-Daley rats, maintained their body temperature
      at 37 +/- 0.5 degrees C, and then observed the survival rate during the post
      resuscitation phase. We examined neuronal damage in the hippocampus using cresyl
      violet (CV) and Fluore-Jade B (F-J B) staining, and pro-inflammatory response
      using ionized calcium-binding adapter molecule 1 (Iba-1), glial fibrillary acidic
      protein (GFAP), and tumor necrosis factor-alpha (TNF-alpha) immunohistochemistry
      in the hippocampus after asphyxial CA in rats under normothermia. Our results
      show that the survival rate decreased gradually post-CA (about 63% at 6 hours,
      37% at 1 day, and 8% at 2 days post-CA). Rats were sacrificed at these points in
      time post-CA, and no neuronal damage was found in the hippocampus until 1 day
      post-CA. However, some neurons in the stratum pyramidale of the CA region in the
      hippocampus were dead 2 days post-CA. Iba-1 immunoreactive microglia in the CA1
      region did not change until 1 day post-CA, and they were activated (enlarged cell
      bodies with short and thicken processes) in all layers 2 days post-CA. Meanwhile,
      GFAP-immunoreactive astrocytes did not change significantly until 2 days post-CA.
      TNF-alpha immunoreactivity decreased significantly in neurons of the stratum
      pyramidale in the CA1 region 6 hours post-CA, decreased gradually until 1 day
      post-CA, and increased significantly again 2 days post-CA. These findings suggest
      that low survival rate of normothermic rats in the early period of asphyxia
      induced CA is related to increased TNF-alpha immunoreactivity, but not to
      neuronal damage in the hippocampal CA1 region.

PMID- 29323040
TI  - D-dimer may predict poor outcomes in patients with aneurysmal subarachnoid
      hemorrhage: a retrospective study.
AB  - Serum biomarkers may play a reliable role in predicting the outcomes of patients
      with aneurysmal subarachnoid hemorrhage. This study retrospectively analyzed the
      relationship between serum biomarkers on admission and outcomes in patients with
      aneurysmal subarachnoid hemorrhage. We recruited 146 patients with aneurysmal
      subarachnoid hemorrhage who were treated in Renmin Hospital of Wuhan University
      of China between 1 May 2014 and 30 March 2016. There were 57 males and 89 females
      included and average age of included patients was 57.03 years old. Serum samples
      were taken immediately on admission (within 48 hours after initial hemorrhage)
      and the levels of serum biomarkers were detected. Baseline information,
      complications, and outcomes at 6 months were recorded. Univariate and
      multivariate logistic regression analyses were used to explore the relationship
      between biomarkers and clinical outcomes. Receiver operating characteristic
      curves were obtained to investigate the possibility of the biomarkers predicting
      prognosis. Of the 146 patients, 102 patients achieved good outcomes and 44
      patients had poor outcomes. Univariate and multivariate analyses showed that high
      World Federation of Neurosurgical Societies grade, high serum D-dimer levels, and
      high neurological complications were significantly associated with poor outcomes.
      Receiver operating characteristic curves verified that D-dimer levels were
      associated with poor outcomes. D-dimer levels strongly correlated with
      neurological complications. In conclusion, we suggest that D-dimer levels are a
      good independent prognostic factor for poor outcomes in patients with aneurysmal
      subarachnoid hemorrhage.

PMID- 29323041
TI  - Central post-stroke pain due to injury of the spinothalamic tract in patients
      with cerebral infarction: a diffusion tensor tractography imaging study.
AB  - Many studies using diffusion tensor tractography (DTT) have demonstrated that
      injury of the spinothalamic tract (STT) is the pathogenetic mechanism of central
      post-stroke pain (CPSP) in intracerebral hemorrhage; however, there is no DTT
      study reporting the pathogenetic mechanism of CPSP in cerebral infarction. In
      this study, we investigated injury of the STT in patients with CPSP following
      cerebral infarction, using DTT. Five patients with CPSP following cerebral
      infarction and eight age- and sex-matched healthy control subjects were recruited
      for this study. STT was examined using DTT. Among DTT parameters of the affected
      STT, fractional anisotropy and tract volume were decreased by more than two
      standard deviations in two patients (patients 1 and 2) and three patients
      (patients 3, 4, and 5), respectively, compared with those of the control
      subjects, while mean diffusivity value was increased by more than two standard
      deviations in one patient (patient 2). Regarding DTT configuration, all affected
      STTs passed through adjacent part of the infarct and three STTs showed narrowing.
      These findings suggest that injury of the STT might be a pathogenetic etiology of
      CPSP in patients with cerebral infarction.

PMID- 29323042
TI  - Mitochondrial protective and anti-apoptotic effects of Rhodiola crenulata extract
      on hippocampal neurons in a rat model of Alzheimer's disease.
AB  - In our previous study, we found that the edible alcohol extract of the root of
      the medicinal plant Rhodiola crenulata (RCE) improved spatial cognition in a rat
      model of Alzheimer's disease. Another study from our laboratory showed that RCE
      enhanced neural cell proliferation in the dentate gyrus of the hippocampus and
      prevented damage to hippocampal neurons in a rat model of chronic stress-induced
      depression. However, the mechanisms underlying the neuroprotective effects of RCE
      are unclear. In the present study, we investigated the anti-apoptotic effect of
      RCE and its neuroprotective mechanism of action in a rat model of Alzheimer's
      disease established by intracerebroventricular injection of streptozotocin. The
      rats were pre-administered RCE at doses of 1.5, 3.0 or 6.0 g/kg for 21 days
      before model establishment. ATP and cytochrome c oxidase levels were
      significantly decreased in rats with Alzheimer's disease. Furthermore, neuronal
      injury was obvious in the hippocampus, with the presence of a large number of
      apoptotic neurons. In comparison, in rats given RCE pretreatment, ATP and
      cytochrome c oxidase levels were markedly increased, the number of apoptotic
      neurons was reduced, and mitochondrial injury was mitigated. The 3.0 g/kg dose of
      RCE had the optimal effect. These findings suggest that pretreatment with RCE
      prevents mitochondrial dysfunction and protects hippocampal neurons from
      apoptosis in rats with Alzheimer's disease.

PMID- 29323043
TI  - Neural computational modeling reveals a major role of corticospinal gating of
      central oscillations in the generation of essential tremor.
AB  - Essential tremor, also referred to as familial tremor, is an autosomal dominant
      genetic disease and the most common movement disorder. It typically involves a
      postural and motor tremor of the hands, head or other part of the body. Essential
      tremor is driven by a central oscillation signal in the brain. However, the
      corticospinal mechanisms involved in the generation of essential tremor are
      unclear. Therefore, in this study, we used a neural computational model that
      includes both monosynaptic and multisynaptic corticospinal pathways interacting
      with a propriospinal neuronal network. A virtual arm model is driven by the
      central oscillation signal to simulate tremor activity behavior. Cortical
      descending commands are classified as alpha or gamma through monosynaptic or
      multisynaptic corticospinal pathways, which converge respectively on alpha or
      gamma motoneurons in the spinal cord. Several scenarios are evaluated based on
      the central oscillation signal passing down to the spinal motoneurons via each
      descending pathway. The simulated behaviors are compared with clinical essential
      tremor characteristics to identify the corticospinal pathways responsible for
      transmitting the central oscillation signal. A propriospinal neuron with strong
      cortical inhibition performs a gating function in the generation of essential
      tremor. Our results indicate that the propriospinal neuronal network is essential
      for relaying the central oscillation signal and the production of essential
      tremor.

PMID- 29323044
TI  - Magnetic resonance imaging-guided focused ultrasound to increase localized blood
      spinal cord barrier permeability.
AB  - Spinal cord injury (SCI) affects thousands of people every year in the USA, and
      most patients are left with some permanent paralysis. Therapeutic options are
      limited and only modestly affect outcome. To address this issue, we used magnetic
      resonance imaging-guided focused ultrasound (MRgFUS) as a non-invasive approach
      to increase permeability in the blood-spinal cord barrier (BSCB). We hypothesize
      that localized, controlled sonoporation of the BSCB by MRgFUS will aid delivery
      of therapeutics to the injury. Here, we report our preliminary findings for the
      ability of MRgFUS to increase BSCB permeability in the thoracic spinal cord of a
      normal rat model. First, an excised portion of normal rat spinal column was used
      to characterize the acoustic field and to estimate the insertion losses that
      could be expected in an MRgFUS blood spinal cord barrier opening. Then, in normal
      rats, MRgFUS was applied in combination with intravenously administered
      microbubbles to the spinal cord region. Permeability of the BSCB was indicated as
      signal enhancement by contrast administered prior to T1-weighted magnetic
      resonance imaging and verified by Evans blue dye. Neurological testing using the
      Basso, Beattie, and Breshnahan scale and the ladder walk was normal in 8 of 10
      rats tested. Two rats showed minor impairment indicating need for further
      refinement of parameters. No gross tissue damage was evident by histology. In
      this study, we have opened successfully the blood spinal cord barrier in the
      thoracic region of the normal rat spine using magnetic resonance-guided focused
      ultrasound combined with microbubbles.

PMID- 29323045
TI  - Does vitamin C have the ability to augment the therapeutic effect of bone marrow
      derived mesenchymal stem cells on spinal cord injury?
AB  - Methylprednisolone (MP) is currently the only drug confirmed to exhibit a
      neuroprotective effect on acute spinal cord injury (SCI). Vitamin C (VC) is a
      natural water-soluble antioxidant that exerts neuroprotective effects through
      eliminating free radical damage to nerve cells. Bone marrow mesenchymal stem
      cells (BMMSCs), as multipotent stem cells, are promising candidates in SCI
      repair. To evaluate the therapeutic effects of MP, VC and BMMSCs on traumatic
      SCI, 80 adult male rats were randomly divided into seven groups: control, SCI
      (SCI induction by weight-drop method), MP (SCI induction, followed by
      administration of 30 mg/kg MP via the tail vein, once every other 6 hours, for
      five times), VC (SCI induction, followed by intraperitoneal administration of 100
      mg/kg VC once a day, for 28 days), MP + VC (SCI induction, followed by
      administration of MP and VC as the former), BMMSCs (SCI induction, followed by
      injection of 3 * 106 BMMSCs at the injury site), and BMMSCs + VC (SCI induction,
      followed by BMMSCs injection and VC administration as the former). Locomotor
      recovery was assessed using the Basso Mouse Scale. Injured spinal cord tissue was
      evaluated using hematoxylin-eosin staining and immunohistochemical staining.
      Expression of transforming growth factor-beta, tumor necrosis factor-alpha, and
      matrix metalloproteinase-2 genes was determined using real-time quantitative PCR.
      BMMSCs intervention better promoted recovery of nerve function of rats with SCI,
      mitigated nerve cell damage, and decreased expression of transforming growth
      factor-beta, tumor necrosis factor-alpha, and matrix metalloproteinase-2 genes
      than MP and/or VC. More importantly, BMMSCs in combination with VC induced more
      obvious improvements. These results suggest that VC can enhance the
      neuroprotective effects of BMMSCs against SCI.

PMID- 29323046
TI  - Non-concomitant cortical structural and functional alterations in sensorimotor
      areas following incomplete spinal cord injury.
AB  - Brain plasticity, including anatomical changes and functional reorganization, is
      the physiological basis of functional recovery after spinal cord injury (SCI).
      The correlation between brain anatomical changes and functional reorganization
      after SCI is unclear. This study aimed to explore whether alterations of cortical
      structure and network function are concomitant in sensorimotor areas after
      incomplete SCI. Eighteen patients with incomplete SCI (mean age 40.94 +/- 14.10
      years old; male:female, 7:11) and 18 healthy subjects (37.33 +/- 11.79 years old;
      male:female, 7:11) were studied by resting state functional magnetic resonance
      imaging. Gray matter volume (GMV) and functional connectivity were used to
      evaluate cortical structure and network function, respectively. There was no
      significant alteration of GMV in sensorimotor areas in patients with incomplete
      SCI compared with healthy subjects. Intra-hemispheric functional connectivity
      between left primary somatosensory cortex (BA1) and left primary motor cortex
      (BA4), and left BA1 and left somatosensory association cortex (BA5) was
      decreased, as well as inter-hemispheric functional connectivity between left BA1
      and right BA4, left BA1 and right BA5, and left BA4 and right BA5 in patients
      with SCI. Functional connectivity between both BA4 areas was also decreased. The
      decreased functional connectivity between the left BA1 and the right BA4
      positively correlated with American Spinal Injury Association sensory score in
      SCI patients. The results indicate that alterations of cortical anatomical
      structure and network functional connectivity in sensorimotor areas were non
      concomitant in patients with incomplete SCI, indicating the network functional
      changes in sensorimotor areas may not be dependent on anatomic structure. The
      strength of functional connectivity within sensorimotor areas could serve as a
      potential imaging biomarker for assessment and prediction of sensory function in
      patients with incomplete SCI. This trial was registered with the Chinese Clinical
      Trial Registry (registration number: ChiCTR-ROC-17013566).

PMID- 29323047
TI  - Diffusion tensor imaging of spinal microstructure in healthy adults: improved
      resolution with the readout segmentation of long variable echo-trains.
AB  - Diffusion tensor imaging plays an important role in the accurate diagnosis and
      prognosis of spinal cord diseases. However, because of technical limitations, the
      imaging sequences used in this technique cannot reveal the fine structure of the
      spinal cord with precision. We used the readout segmentation of long variable
      echo-trains (RESOLVE) sequence in this cross-sectional study of 45 healthy
      volunteers aged 20 to 63 years. We found that the RESOLVE sequence significantly
      increased the resolution of the diffusion images and improved the median signal
      to-noise ratio of the middle (C4-6) and lower (C7-T1) cervical segments to the
      level of the upper cervical segment. In addition, the values of fractional
      anisotropy and radial diffusivity were significantly higher in white matter than
      in gray matter. Our study verified that the RESOLVE sequence could improve
      resolution of diffusion tensor imaging in clinical applications and provide
      accurate baseline data for the diagnosis and treatment of cervical spinal cord
      diseases.

PMID- 29323048
TI  - Topiramate as a neuroprotective agent in a rat model of spinal cord injury.
AB  - Topiramate (TPM) is a widely used antiepileptic and antimigraine agent which has
      been shown to exert neuroprotective effects in various experimental traumatic
      brain injury and stroke models. However, its utility in spinal cord injury has
      not been studied extensively. Thus, we evaluated effects of TPM on secondary
      cellular injury mechanisms in an experimental rat model of traumatic spinal cord
      injury (SCI). After rat models of thoracic contusive SCI were established by free
      weight-drop method, TPM (40 mg/kg) was given at 12-hour intervals for four times
      orally. Post TPM treatment, malondialdehyde and protein carbonyl levels were
      significantly reduced and reduced glutathione levels were increased, while
      immunoreactivity for endothelial nitric oxide synthase, inducible nitric oxide
      synthase, and apoptotic peptidase activating factor 1 was diminished in SCI rats.
      In addition, TPM treatment improved the functional recovery of SCI rats. This
      study suggests that administration of TPM exerts neuroprotective effects on SCI.

PMID- 29323049
TI  - Autologous transplantation with fewer fibers repairs large peripheral nerve
      defects.
AB  - Peripheral nerve injury is a serious disease and its repair is challenging. A
      cable-style autologous graft is the gold standard for repairing long peripheral
      nerve defects; however, ensuring that the minimum number of transplanted nerve
      attains maximum therapeutic effect remains poorly understood. In this study, a
      rat model of common peroneal nerve defect was established by resecting a 10-mm
      long right common peroneal nerve. Rats receiving transplantation of the common
      peroneal nerve in situ were designated as the in situ graft group. Ipsilateral
      sural nerves (10-30 mm long) were resected to establish the one sural nerve graft
      group, two sural nerves cable-style nerve graft group and three sural nerves
      cable-style nerve graft group. Each bundle of the peroneal nerve was 10 mm long.
      To reduce the barrier effect due to invasion by surrounding tissue and connective
      tissue overgrowth between neural stumps, small gap sleeve suture was used in both
      proximal and distal terminals to allow repair of the injured common peroneal
      nerve. At three months postoperatively, recovery of nerve function and morphology
      was observed using osmium tetroxide staining and functional detection. The
      results showed that the number of regenerated nerve fibers, common peroneal nerve
      function index, motor nerve conduction velocity, recovery of myodynamia, and wet
      weight ratios of tibialis anterior muscle were not significantly different among
      the one sural nerve graft group, two sural nerves cable-style nerve graft group,
      and three sural nerves cable-style nerve graft group. These data suggest that the
      repair effect achieved using one sural nerve graft with a lower number of nerve
      fibers is the same as that achieved using the two sural nerves cable-style nerve
      graft and three sural nerves cable-style nerve graft. This indicates that
      according to the 'multiple amplification' phenomenon, one small nerve graft can
      provide a good therapeutic effect for a large peripheral nerve defect.

PMID- 29323050
TI  - Long non-coding RNA NONMMUG014387 promotes Schwann cell proliferation after
      peripheral nerve injury.
AB  - Schwann cells play a critical role in peripheral nerve regeneration through
      dedifferentiation and proliferation. In a previous study, we performed microarray
      analysis of the sciatic nerve after injury. Accordingly, we predicted that long
      non-coding RNA NONMMUG014387 may promote Schwann cell proliferation after
      peripheral nerve injury, as bioinformatic analysis revealed that the target gene
      of NONMMUG014387 was collagen triple helix repeat containing 1 (Cthrc1). Cthrc1
      may promote cell proliferation in a variety of cells by activating Wnt/PCP
      signaling. Nonetheless, bioinformatic analysis still needs to be verified by
      biological experiment. In this study, the candidate long non-coding RNA,
      NONMMUG014387, was overexpressed in mouse Schwann cells by recombinant adenovirus
      transfection. Plasmid pHBAd-MCMV-GFP-NONMMUG014387 and pHBAd-MCMV-GFP were
      transfected into Schwann cells. Schwann cells were divided into three groups:
      control (Schwann cells without intervention), Ad-GFP (Schwann cells with GFP
      overexpression), and Ad-NONMMUGO148387 (Schwann cells with GFP and NONMMUGO148387
      overexpression). Cell Counting Kit-8 assay was used to evaluate proliferative
      capability of mouse Schwann cells after NONMMUG014387 overexpression. Polymerase
      chain reaction and western blot assay were performed to investigate target genes
      and downstream pathways of NONMMUG014387. Cell proliferation was significantly
      increased in Schwann cells overexpressing lncRNA NONMMUG014387 compared with the
      other two groups. Further, compared with the control group, mRNA and protein
      levels of Cthrc1, Wnt5a, ROR2, RhoA, Rac1, JNK, and ROCK were visibly up
      regulated in the Ad-NONMMUGO148387 group. Our findings confirm that long non
      coding RNA NONMMUG014387 can promote proliferation of Schwann cells surrounding
      the injury site through targeting Cthrc1 and activating the Wnt/PCP pathway.

PMID- 29323051
TI  - Notch pathway inhibitor DAPT enhances Atoh1 activity to generate new hair cells
      in situ in rat cochleae.
AB  - Atoh1 overexpression in cochlear epithelium induces new hair cell formation. Use
      of adenovirus-mediated Atoh1 overexpression has mainly focused on the rat lesser
      epithelial ridge and induces ectopic hair cell regeneration. The sensory region
      of rat cochlea is difficult to transfect, thus new hair cells are rarely produced
      in situ in rat cochlear explants. After culturing rat cochleae in medium
      containing 10% fetal bovine serum, adenovirus successfully infected the sensory
      region as the width of the supporting cell area was significantly increased.
      Adenovirus encoding Atoh1 infected the sensory region and induced hair cell
      formation in situ. Combined application of the Notch inhibitor DAPT and Atoh1
      increased the Atoh1 expression level and decreased hes1 and hes5 levels, further
      promoting hair cell generation. Our results demonstrate that DAPT enhances Atoh1
      activity to promote hair cell regeneration in rat cochlear sensory epithelium in
      vitro.

PMID- 29323052
TI  - Quantification of intermuscular and intramuscular adipose tissue using magnetic
      resonance imaging after neurodegenerative disorders.
AB  - Ectopic adiposity has gained considerable attention because of its tight
      association with metabolic and cardiovascular health in persons with spinal cord
      injury (SCI). Ectopic adiposity is characterized by the storage of adipose tissue
      in non-subcutaneous sites. Magnetic resonance imaging (MRI) has proven to be an
      effective tool in quantifying ectopic adiposity and provides the opportunity to
      measure different adipose depots including intermuscular adipose tissue (IMAT)
      and intramuscular adipose tissue (IntraMAT) or intramuscular fat (IMF). It is
      highly important to distinguish and clearly define these compartments, because
      controversy still exists on how to accurately quantify these adipose depots.
      Investigators have relied on separating muscle from fat pixels based on their
      characteristic signal intensities. A common technique is plotting a threshold
      histogram that clearly separates between muscle and fat peaks. The cut-offs to
      separate between muscle and fat peaks are still not clearly defined and different
      cut-offs have been identified. This review will outline and compare the Midpoint
      and Otsu techniques, two methods used to determine the threshold between muscle
      and fat pixels on T1 weighted MRI. The process of water/fat segmentation using
      the Dixon method will also be outlined. We are hopeful that this review will
      trigger more research towards accurately quantifying ectopic adiposity due to its
      high relevance to cardiometabolic health after SCI.

PMID- 29323054
TI  - From Editor's desk.

PMID- 29323055
TI  - Immunohistochemical and molecular markers in urothelial carcinoma.

PMID- 29323053
TI  - Roles of neural stem cells in the repair of peripheral nerve injury.
AB  - Currently, researchers are using neural stem cell transplantation to promote
      regeneration after peripheral nerve injury, as neural stem cells play an
      important role in peripheral nerve injury repair. This article reviews recent
      research progress of the role of neural stem cells in the repair of peripheral
      nerve injury. Neural stem cells can not only differentiate into neurons,
      astrocytes and oligodendrocytes, but can also differentiate into Schwann-like
      cells, which promote neurite outgrowth around the injury. Transplanted neural
      stem cells can differentiate into motor neurons that innervate muscles and
      promote the recovery of neurological function. To promote the repair of
      peripheral nerve injury, neural stem cells secrete various neurotrophic factors,
      including brain-derived neurotrophic factor, fibroblast growth factor, nerve
      growth factor, insulin-like growth factor and hepatocyte growth factor. In
      addition, neural stem cells also promote regeneration of the axonal myelin
      sheath, angiogenesis, and immune regulation. It can be concluded that neural stem
      cells promote the repair of peripheral nerve injury through a variety of ways.

PMID- 29323056
TI  - Role of salivary biomarkers in early detection of oral squamous cell carcinoma.
AB  - INTRODUCTION: Oral cancer is prevalent worldwide and is a common cause of
      morbidity and mortality. Despite advances in treatment, the survival of patients
      with oral cancer has not significantly improved over the past several decades
      owing to late detection and treatment failures. The present study was undertaken
      with an objective to explore the role of salivary CYFRA 21-1, CA 19-9, lactate
      dehydrogenase (LDH), total proteins, and amylase as biochemical markers of oral
      squamous cell carcinoma (OSCC) and premalignant lesions (PML). MATERIALS AND
      METHODS: This was a cross-sectional study for diagnostic test evaluation
      conducted in KGMC Lucknow, between 2010 and 2011. The study population comprised
      newly diagnosed cases of OSCC (Group I) and PML of oral cavity (Group II) who had
      not yet received any definitive therapy along with age- and gender-matched
      healthy controls (Group III). Unstimulated whole saliva was collected from the
      cases and controls. CYFRA 21-1 and CA19-9 were estimated by ELISA while LDH,
      total proteins, and amylase were evaluated as per standard kit method. RESULTS:
      Both OSCC and PML group showed increased salivary CYFRA 21-1, LDH, and total
      protein concentrations as compared to controls, but the increase in PML was
      significantly lower as compared to OSCC. A considerable decrease in concentration
      of amylase was seen in OSCC and PML as compared to control group. CONCLUSION: The
      outcome of this study suggests that concurrent analysis of salivary CYFRA 21-1,
      LDH, total protein, and amylase can be utilized for early detection of oral
      cancer.

PMID- 29323057
TI  - Hypoxia-induced factor-1 alpha, vascular endothelial growth factor expression in
      BRCA1-related breast cancer: A prospective study in tertiary care hospital.
AB  - INTRODUCTION: Breast cancer is the commonest cause of death among middle aged
      women. BRCA1 associated tumors carry a poor prognosis. Angiogenesis is considered
      necessary for tumor growth and for its metastasis. Hypoxia stimulates HIF-1alpha
      which then activates transcription of various proangiogenic cytokines like VEGF.
      In the present study we examined HIF-1alpha expression, sVEGF levels and BRCA1
      mutations and their relation with clinicopathological parameters. We also
      determined whether the angiogenic markers have different role in angiogenesis in
      BRCA1 related cancers as compared to sporadic breast cancers. MATERIALS AND
      METHODS: The study was conducted on 50 cases of breast cancer specimens.
      Histopathological typing and grading was done followed by immunohistochemistry
      for BRCA1 and HIF-1alpha. VEGF was done in the serum by ELISA. RESULTS: All the
      tumors were infiltrating ductal carcinoma NOS. 16 cases were reported grade II
      and 34 cases as grade III. On immunohistochemistry, 27 cases showed BRCA1
      positivity and HIF-1alpha was positive in 39 cases. sVEGF levels were increased
      in 21 cases (42%). BRCA1 positivity, HIF-1alpha expression and increased VEGF
      levels were significantly associated with higher grade and lymph node metastasis.
      There was significant correlation of BRCA1 positivity with increased HIF-1alpha
      expression (P = 0.009) and increased sVEGF levels (P = 0.005). CONCLUSION: Our
      findings suggest that BRCA 1 positive tumors have unique molecular profile and
      different mechanism of tumorigenesis. Such tumors are associated with increased
      HIF-1alpha expression and VEGF levels.

PMID- 29323058
TI  - Assessment of topoisomerase II-alpha gene status by dual color chromogenic in
      situ hybridization in a set of Iraqi patients with invasive breast carcinoma.
AB  - BACKGROUND: The human epidermal growth factor receptor 2(HER2) proto-oncogene is
      overexpressed or amplified in approximately 15%-25% of invasive breast cancers.
      Approximately 35% of HER2-amplified breast cancers have coamplification of the
      topoisomerase II-alpha (TOP2A) gene encoding an enzyme that is a major target of
      anthracyclines. Hence, the determination of genetic alteration (amplification or
      deletion) of both genes is considered as an important predictive factor that
      determines the response of breast cancer patients to treatment. The aims of this
      study are to determinate TOP2A status gene amplification in a set of Iraqi
      patients with breast cancer that have had an equivocal (2+) and positive HER2/neu
      by immunohistochemistry (IHC) and to compare the results with estrogen receptor
      (ER) and progesterone receptor (PR) and HER2/neu status. PATIENTS AND METHODS: A
      cross-sectional prospective study done on 53 patients with invasive breast
      carcinoma. Twenty-six out of total 53 cases were positive HER2/neu (3+), the
      remaining 27 equivocal HER2-IHC (2+) cases reanalyzed using dual-color
      chromogenic in situ hybridization (ZytoVision) probe kit for further
      identification of HER2/neu gene amplification. Using chromogenic in situ
      hybridization (CISH), TOP2A gene status determination was done for all cases.
      RESULTS: There is a direct significant correlation between TOP2A gene
      amplification and HER2/neu positivity, P < 0.05 in that 15 (39.4%) out of 38
      positive HER2/neu cases were associated with topoisomerase gene amplification.
      Regarding relation of topoisomerase gene to hormone receptor status (ER and PR),
      there was a significant negative relationship between the gene and ER receptor
      status. The higher level of gene amplification was noticed in ER and PR negative
      cases in about 13 (43.3%) and 14 (48.2%) for ER and PR, respectively. CONCLUSION:
      TOP2A gene status has a significantly positive correlation with HER2/neu status
      while it has a significantly negative correlation with hormone receptor status.

PMID- 29323059
TI  - Histological and morphometric analysis of dilated cardiomyopathy with special
      reference to collagen IV expression.
AB  - INTRODUCTION: Collagen distribution alterations are well known in dilated
      cardiomyopathy. There are also changes in microvasculature along with other
      histomorphorphological features. AIMS AND OBJECTIVES: To study the
      histomorphological features of DCM along with their quantitative correlation with
      LVEF. Alterations in collagen IV distribution pattern and microvasculature in DCM
      were also evaluated. MATERIALS AND METHODS: The present study includes 34 right
      ventricular endomyocardial biopsies, 7 explanted native hearts and 41 autopsy
      control hearts. Sections were taken from lower half of right interventricular
      septum and stained for H and E, Masson trichrome and immunohistochemistry for
      CD34, SMA and Collagen IV to study the histological features, pattern of
      fibrosis, capillary and arteriolar distribution and collagen IV expression
      respectively. Morphometric analysis was carried out in all cases and controls
      using Image analysis software Image pro plus 7 and correlated with left
      ventricular ejection fraction. RESULTS: The histomorphological changes of DCM
      include myocyte hypertrophy, nucleomegaly, and interstitial fibrosis. Interfiber
      fibrosis was the commonest. There was evidence of myocarditis, ischemic change
      and vessel wall alterations. Considerable alteration in Collagen IV distribution
      was observed with reduction in intensity and proportion of staining around
      myocytes quantified using Allred scoring against uniform pericellular staining in
      controls. Morphometric analysis revealed significant increase in nuclear area,
      myocyte width, percentage of fibrosis and reduction in capillary myocyte ratio in
      cases as compared to controls. There was no significant difference in arteriolar
      density. No significant association was observed between morphometric parameters
      and LVEF. CONCLUSION: Histomorphological changes in DCM are non-specific.
      Quantitation of histological parameters cannot be used to predict the disease
      progression as there was no significant correlation with LVEF. There is
      appreciable alteration in Collagen IV distribution in DCM owing to extracellular
      matrix alterations.

PMID- 29323060
TI  - Spectrum of hepatobiliary cystic lesions: A 7-year experience at a tertiary care
      referral center in North India and review of literature.
AB  - CONTEXT: Cysts arising from the hepatobiliary tree are a group of heterogeneous
      lesions with regard to pathogenesis, clinical presentation, and radiological
      finding. They can be intrahepatic or extrahepatic, developmental, secondary to
      infective/inflammatory etiologies, as well as neoplastic. This study was
      conducted to determine the spectrum of hepatobiliary cysts in surgically
      intervened cases, with regard to their prevalence, histological spectrum, and
      clinicoradiological correlation, wherever possible. METHODS: In this
      retrospective observational study, hematoxylin and eosin stained slides of all
      cases of hepatobiliary cystic lesions, operated between 2009 and 2016 were
      reviewed. Special stains as reticulin, Masson's trichrome, and periodic acid
      Schiff were done wherever necessary. Overall prevalence, age-sex distribution,
      clinical presentation and histopathological patterns were studied. Relevant
      imaging findings were correlated wherever possible. RESULTS: A total of 312 cases
      of hepatobiliary cysts were identified, the majority in females. Choledochal
      cysts (CCs) were the most common type (n = 198,63.5%), followed by hydatid cysts
      (n = 73,23.3%), simple hepatic cysts (n = 10,3.2%), congenital hepatic fibrosis
      (n = 10,3.2%), biliary cystadenomas (n = 4,1.2%) hepatic mesenchymal hamartomas
      (n = 7,2.2%), and cavernous hemangiomas (n = 3,0.9%). Fibropolycystic liver
      disease (n = 2,0.6%), Caroli's disease (n = 1, 0.3%), liver abscess (n = 2,
      0.6%), infantile hemangioendothelioma (n = 1,0.3%), and biliary
      cystadenocarcinomas (n = 1,0.3%) were rare. Lesions noted mostly in 1st decade of
      life were: CCs, fibrocystic liver disease, Caroli's syndrome, cystic mesenchymal
      hamartoma, and infantile hemangioendotheliomas. CONCLUSION: In our cohort of
      surgically intervened cases of hepatobiliary cystic lesions from a tertiary care
      hospital in North India, the CCs, followed by hydatid cyst were the most common
      lesions. Histology can play vital role in characterization, as often clinical
      findings and radiology can overlap.

PMID- 29323061
TI  - Accuracy of vascular invasion reporting in hepatocellular carcinoma before and
      after implementation of subspecialty surgical pathology sign-out.
AB  - CONTEXT: Liver cancers (including hepatocellular carcinoma [HCC] and
      cholangiocarcinoma) are the fifth most common cause of cancer death. The most
      powerful independent histologic predictor of overall survival after
      transplantation for HCC is the presence of microscopic vascular invasion (VI).
      AIMS: Given that VI is known to have somewhat high interobserver variability in
      both HCC and other tumors, we hypothesized that pathologists with special
      interest and training in liver pathology would be more likely to identify and
      report VI in HCC than would general surgical pathologists. SETTINGS AND DESIGN:
      We searched our departmental surgical pathology archives for transplant
      hepatectomies performed for HCC. SUBJECTS AND METHODS: We identified 143 such
      cases with available sign-out reports and hematoxylin and eosin-stained slides.
      STATISTICAL ANALYSIS USED: Kappa results (level of agreement) were calculated.
      RESULTS: Before surgical pathology subspecialty sign-out (SSSO) implementation,
      49 of 88 HCC cases were reported as negative for VI; on rereview, 20 of these had
      VI. After SSSO implementation, 39 of 55 cases were reported as negative for VI;
      on our review, 8 of these had VI. Kappa (agreement) between general SO and
      subspecialty rereview was 0.562 (95% confidence interval [CI] = 0.411-0.714)
      "weak agreement." Kappa (agreement) between SSSO and rereview by select liver
      pathologists was 0.693 (95% CI = 0.505-0.880) "moderate agreement." CONCLUSIONS:
      Our study is one of only a few so far that have suggested improved accuracy of
      certain parameters under SSSO.

PMID- 29323062
TI  - Role of p53 and Ki-67 immunomarkers in carcinoma of urinary bladder.
AB  - BACKGROUND: Urothelial carcinoma is common urinary malignancy responsible for a
      significant proportion of cancer morbidity and mortality. We carried out the
      present study to demonstrate the clinicohistopathological features and to
      correlate the p53 and Ki-67 immunoexpression with grade and stage of bladder
      carcinomas. MATERIALS AND METHODS: We investigated 110 cases of bladder tumor.
      Grading and staging were done according to the WHO-2004 and American Joint
      Committee on Cancer-TNM staging recommendations. Immunohistochemical staining for
      p53 and Ki-67 was performed in all the cases, categorized as high and low
      expression taking 20% positivity as cutoff value. Statistical analysis was done
      using McNemar's Chi-square test and Fisher's exact test. RESULTS: There were 61
      cases of high grade and 49 cases of low grade exhibiting urothelial carcinoma as
      the most common variant (97.3%). Muscle invasive carcinomas (pT2) noted in 29
      cases whereas 23 and 58 cases revealed stage pTa and pT1, respectively.
      Evaluation of p53 and Ki-67 immunoexpression showed a significant association
      with histological grade and stage individually and also in combination (P <
      0.05). CONCLUSION: Our results corroborate with the opinion that combined use of
      p53 and Ki-67 immunomarkers may provide additional prognostic information along
      with histological grading and staging in bladder carcinomas.

PMID- 29323063
TI  - Evaluation of MUC1 and P53 expressions in noninvasive papillary urothelial
      neoplasms of bladder, their relationship with tumor grade and role in the
      differential diagnosis.
AB  - PURPOSE: The aim of this study was to investigate the usability of MUC1 and p53
      for differential diagnosis of noninvasive papillary urothelial neoplasias,
      especially for distinguishing papillary urothelial neoplasm of low malignant
      potential (PUNLMP) from low-grade papillary urothelial carcinoma (LGPUC) when the
      histologic signs are not obvious. MATERIALS AND METHODS: Seventeen biopsy
      specimens of the patients with PUNLMP, 20 with LGPUC and 13 with high-grade
      papillary urothelial carcinoma (HGPUC) were stained for MUC1 and p53 protein by
      immunohistochemical methods. Histological grading was performed according to an
      algorithm, which allows histological parameters used in 2004 WHO/ISUP 1998.
      RESULTS: We had obvious statistical difference for aberrant expression pattern of
      MUC1 between PUNLMP and LGPUC-HGPUC (P = 0.007). Positivity of MUC1 expression in
      cytoplasm of basal cells was more observed in HGPUC and LGPUC, whereas PUNLMP was
      more often showing apical and superficial positivity of MUC1 expression (P =
      0.001 and 0.011). Nuclear p53 protein in HGPUC was obviously more frequent than
      that in LGPUC and PUNLMP (P < 0.001). Measures showed statistical difference
      among aberrant MUC1 expression, p53 overexpression, and tumor grade (P < 0.001).
      CONCLUSIONS: MUC1 and p53 may be helpful immunohistochemical markers for
      distinguishing PUNLMP from LGPUC and HGPUC, when the histologic signs are not
      obvious.

PMID- 29323064
TI  - Vascular endothelial growth factor expression in placenta of hypertensive
      disorder in pregnancy.
AB  - INTRODUCTION: Hypertensive disorder in pregnancy (HDP) represents the most common
      medical complication in pregnancy. It is the leading cause of maternal and
      perinatal mortality and morbidity. Vascular endothelial growth factor (VEGF)
      stimulates vascular endothelial cell growth, survival, and proliferation, and
      they are known to be expressed in human placenta. The aim of this study was to
      determine the VEGF expression in the placenta of hypertensive and normotensive
      patients. MATERIALS AND METHODS: This is a retrospective, cross-sectional study
      from January 1, 2015 to December 31, 2015. A total of 30 placentae comprised of
      15 hypertensive and 15 normotensive cases were assessed. VEGF expression in
      placenta was assessed by immunohistochemistry, and the number of syncytial knots
      was counted. RESULTS: Our study showed an increased syncytial knot formation in
      the placenta of hypertensive mothers. VEGF expression was seen in
      syncytiotrophoblasts of 14 of the hypertensive cases (14/15, 93.3%), while only
      two of the normotensive cases were positive (2/15, 13.3%). There were no
      statistically significant differences in VEGF expression in other placenta cells,
      that is, cytotrophoblasts (P = 1.0), decidual cells (0.1394), maternal
      endothelial cells (0.5977), and fetal endothelial cells (P = 1.0). CONCLUSIONS:
      This study showed an increased number of syncytial knots is a consistent
      histological finding in the placenta of patient with HDP. VEGF expression was
      significantly increased in syncytiotrophoblasts in placenta of hypertensive
      group, and it could be used as a biomarker for hypertension.

PMID- 29323065
TI  - Emerging role of preputial vascular pattern and postoperative microvessel density
      in cases of proximal hypospadias: A pilot study.
AB  - INTRODUCTION: Understanding of anatomical vascular patterns and anatomy of
      prepuce is critical for a good outcome in hypospadias surgery. A well
      vascularized neourethral and preputial flaps used for repair are exceptionally
      important for a successful outcome, especially in cases of proximal hypospadias
      undergoing one-stage procedures. OBJECTIVE: To evaluate the vascular anatomy of
      prepuce in cases of proximal hypospadias and to evaluate microvessel density
      (MVD) by immunohistochemistry and its correlation with postoperative
      complications. MATERIAL AND METHODS: This was a prospective observational study
      done between November 2013 and March 2015; 33 cases of proximal hypospadias
      undergoing surgery were evaluated for vascular pattern by intraoperative cold
      light method and postoperatively by MVD. RESULTS: Twenty-six cases with a
      predominant vessel pattern were identified (18 of type 1, 7 of type 2, and 1 of
      type 3), while seven cases had a reticular pattern (type 4) on cold light
      transillumination. The mean MVD in cases with predominant vascular pattern (Type
      1-3) was 64.83. In cases of Type 4 pattern, mean MVD was found to be low 55.57 (P
      = 0.37). Patients who underwent single-stage surgery and developed postoperative
      complications had a low MVD score (mean 45.88, P = 0.040). CONCLUSION: Cold light
      transillumination is an effective perioperative test, reliable in the assessment
      of preputial vascularity. There is no statistically significant difference
      between the MVD of predominant vascular pattern and reticular pattern signifying
      that MVD may or may not be good in a given vascular pattern. MVD can be a helpful
      marker in assessing prognosis of repair in proximal hypospadias.

PMID- 29323066
TI  - Familiar trespassers in histopathology: An obstacle in diagnosis? A single-blind
      study.
AB  - BACKGROUND: Histopathologists encounter strange structures in tissue sections
      that appear unrelated to tissues, and these artifacts may be misinterpreted and
      misdiagnosed as pathological lesions. These substances may either be present
      within the tissues or can get implanted into tissue during biopsy procedure or
      laboratory handling or processing. AIMS: The aim of this study is to observe the
      microscopic appearance of different abnormal structures like commonly implanted
      food particles or easily incorporated substances during tissue processing with
      their probable histological misdiagnosis. MATERIALS AND METHODS: Certain food
      particles, suture materials, wood pieces, insects, and filter paper were
      intentionally introduced in the tissue specimens of uterus and lung. Following
      routine processing and hematoxylin and eosin staining, the slides were subjected
      to single-blind study and viewed under light and polarizing microscope. RESULTS:
      The vivid appearances of these structures lead to histological misdiagnosis.
      CONCLUSION: Knowledge and familiarity of these commonly encountered extraneous
      substances will help to prevent misinterpretation.

PMID- 29323067
TI  - Modified Cajal's trichrome stain as a diagnostic aid in the study of epithelial
      pathology.
AB  - BACKGROUND: Diagnosis of initial epithelial pathology maybe difficult in Squamous
      Cell Carcinoma (SCC), Carcinoma In Situ and other atypical epithelial
      malignancies, under routine Haematoxylin and Eosin (H and E) stain. The detection
      of minor basement membrane alterations in doubtful cases is both time consuming
      and confusing. AIMS: To evaluate efficacy of Modified Cajal's Trichrome Stain
      (CTS) in relation to Haematoxylin and Eosin for study of epithelial dysplasia,
      carcinoma in situ, micro invasive SCC, frank SCC, and SCC in lymph nodes.
      MATERIALS AND METHODS: Formalin-fixed, paraffin-embedded tissue blocks of mild
      epithelial dysplasia (n = 2), moderate epithelial dysplasia (n = 2), severe
      epithelial dysplasia (n = 4), carcinoma in situ (n = 1), micro-invasive SCC (n =
      4), verrucous carcinoma (n = 1), and frank OSCC (n = 5) were stained with CTS and
      H&E. The sections were compared based on set histopathological criteria. RESULTS
      AND CONCLUSION: In SCC cases stained with CTS, invasion into connective tissue
      and keratin pearls were strikingly evident. Depth of invasion could be more
      accurately determined. Tumour cells in lymph node were intensely contrasted and
      easily discernible. Thus, CTS is a good differential stain, clearly delineating
      the epithelial elements from the connective tissue elements visually. This helps
      in tracing the basement membrane very clearly. It is an economic, rapid and easy
      to use method which cannot replace Haematoxylin and Eosin stain in cancer
      diagnosis, but can definitely be used adjunctive to it. Prompt diagnosis is
      crucial to effective treatment, and this stain assists in early and rapid
      diagnosis of cancer.

PMID- 29323068
TI  - Story of survival in anaplastic large cell lymphoma - sometimes more than the
      anaplastic lymphoma kinase status: An evaluation of pathologic prognostic factors
      in 102 cases.
AB  - INTRODUCTION: Systemic anaplastic large cell lymphoma (ALCL) accounts for 5%-10%
      of adult non Hodgkin's lymphoma (NHL) and 10%-30% of childhood NHL. Owing to
      significant differences in survival and gene expression profile, current WHO
      classifies ALCL into two distinct entities as anaplastic lymphoma receptor
      tyrosine kinase (ALK) positive and ALK negative ALCL with ALK expression by
      tumour as a good prognostic indicator. However, in our institute which is a
      cancer referral institute, our preliminary experience was that even ALK positive
      tumours did not fare well as compared to ALK- negative ALCL. So, the current
      study aims at exploring more clinical and pathological factors impacting survival
      in ALCL patients. OBJECTIVE: To study clinical and pathological prognostic
      factors in cases of ALCL. METHODS: 102 cases of ALCL were retrieved from
      pathology database. Pathological features and clinical features of these cases
      were recorded and factors found to impact overall survival (OAS) and disease-free
      survival (DFS) curves were identified based on univariate and multivariate
      analysis. RESULTS: ALK 1 expression was seen in 71/102 (69.6%) cases and was not
      found to impact OAS or DFS. The 2 year OAS rate for ALK positive patients was
      63.5% and DFS rate was 54.4%, while for ALK negative patients, the OAS was 60.5%
      and DFS was 43.5%. The Ann Arbor stage, performance status, international
      prognostic index, histological subtype, and the degree of the background
      inflammatory infiltrate were found to impact the OAS significantly. Increased
      reactive inflammatory component also negatively impacted DFS. In the multivariate
      analysis, only the histologic type emerged as significant for OAS. CONCLUSION:
      Though ALK plays a role in prognostication of systemic ALCL, advanced stage
      disease and an inflammatory milieu may modulate the final outcome. We report a
      study of clinical and pathologic prognostic features in 102 cases of anaplastic
      large cell lymphoma (ALCL) from a cancer referral institute in India. Anaplastic
      lymphoma receptor tyrosine kinase (ALK-1) expression was seen in 71/102 (69.6%)
      cases and was not found to impact overall survival (OAS) or disease-free survival
      (DFS). The 2-year OAS rate for ALK-positive patients was 63.5% and DFS rate was
      54.4%, while for ALK-negative patients, the OAS was 60.5% and DFS was 43.5%. The
      Ann Arbor stage, performance status, international prognostic index, histological
      subtype, and the degree of the background inflammatory infiltrate were found to
      impact the OAS significantly. Increased reactive inflammatory component also
      negatively impacted DFS. In the multivariate analysis, only the histologic type
      emerged as significant for OAS. Thus, though ALK plays a role in prognostication
      of systemic ALCL, advanced stage disease and an inflammatory milieu may modulate
      the final outcome.

PMID- 29323069
TI  - Recurrent dermatophytosis: A rising problem in Sikkim, a Himalayan state of
      India.
AB  - Changing pattern of dermatophytic infection among people of Sikkim over the past
      few years and its recurrence rate has brought a need to do a study on clinical
      pattern and its recurrence from this part of the country. The objectives of this
      study are to discern the clinical patterns of dermatophytosis, identification of
      the isolated fungi to its species level and to see the pattern of its recurrence.
      The study was carried out from January 2015 to May 2016. A total of 192 samples
      were collected from the patients with clinical findings of dermatophytic
      infection. Required history of the patients was taken, followed by clinical
      examination of the lesions and sample collection. The samples were processed for
      mycological study till species identification and a follow up of patients were
      done to assess its recurrence pattern. The age distribution of the patients was
      from 2 to 80 years. The mean and median age was 30.33 and 33 years respectively.
      The male female ratio was 1.8:1. Dermatophytosis was noted more commonly in
      students (n = 64, 33.33%) and jawans (n = 44, 22.92%). Maximum occurrence was
      noted from April to July (n = 106, 55.20%) and was seen mainly in young Hindu
      males. Tinea corporis (n = 104, 54.16%) was the most common clinical
      manifestation followed by tinea unguium (n = 30, 15.63%). T. mentagrophyte (40%)
      was the most common species followed by T. schoenleinii (33.3%), T. tonsurans
      (16.6%) and T. rubrum (6.6%). The recurrence rate was seen most commonly in
      clinical cases of tinea faciei 100%, followed by tinea pedis 80% and tinea
      unguium 46.6%. Overall clinical cure rate was 58.3% and recurrence rate was
      34.3%. In the isolated species of dermatophytes, the recurrence rate was 73.68%
      and that of non-dermatophytes it was 28.07%. Dermatophytosis is an important
      health problem with high recurrence in Sikkim with difference in the etiological
      agent from other parts of India.

PMID- 29323070
TI  - Is diabetes mellitus an important risk factor for the antibiotic resistance in
      extraintestinal pathogenic Escherichia coli?
AB  - Escherichia coli is a major cause of extraintestinal infections in all age group.
      However, the infection becomes more severe when patients have some underlying
      condition such as Diabetes Mellitus. The aim of the study was to determine
      whether diabetic mellitus may act as an important risk factor for the E. coli to
      express drug resistance property. This descriptive study was carried out in a
      multi-specialty tertiary care hospital. One hundred and twenty-seven E. coli
      isolates from diabetic patients, and one hundred seventy-three isolates from
      nondiabetic patients were studied. Possession drug resistance genes were
      determined by multiplex polymerase chain reaction (PCR). Phylogenetic analysis
      was performed by triplex PCR. Antibiotic sensitivity testing was performed by
      Kirby-Bauer disk diffusion method. Among the study isolates from Diabetic
      patients maximum numbers were from phylogroup B2 (42.5%) and D (33%) similarly in
      case of nondiabetic patients B2 (29%) and D (38%) were the most common
      phylogroup. Presence of drug resistance genes among the diabetic and nondiabetic
      patient's isolates were as followed extended-spectrum beta-lactamase (70% and
      70.5%) AmpC (9.5% and 14.5%) and NDM-1 ( 7% and 4.5%) and by disk diffusion
      methods susceptibility pattern were meropenem (94% and 94%), imipenem (92% and
      92%), amikacin (76% and 74%), and ampicillin/sulbactam (68% and 69%),
      respectively. The proportion of diabetic patients strains with the drug
      resistance characteristics were not significantly different from that seen in
      nondiabetic patients strains, which indicating that in a predisposed host
      additional or subtraction bacterial aids for drug resistance property are not a
      necessity.

PMID- 29323071
TI  - Scedosporium apiospermum, an emerging pathogen in India: Case series and review
      of literature.
AB  - Scedosporium apiospermum is a rare cause of infection but is increasingly being
      reported among immunocompromised individuals around the world. We report two
      cases of S. apiospermum, one of keratitis and the other of nasal polyp both from
      immunocompetent patients. The two cases were successfully treated with
      voriconazole. It is important to diagnose such infections as their antifungal
      susceptibility to amphotericin B is variable.

PMID- 29323072
TI  - Orofacial granulomatosis: A disease or a concealed warning.??
AB  - Granulomatosis is any condition characterized by the formation of multiple
      nodules or granulomas in the soft tissues. Differential diagnosis for orofacial
      region includes a wide spectrum of diseases, but most of these lesions present
      histopathologically as noncaseating granulomas, giving a nonspecific depiction
      and leading to a diagnostic impasse. In the absence of any diagnosable entity,
      the disease is labelled as "orofacial granulomatosis". A nine-year-old girl child
      reported with recurrent gingival enlargement and persistent macrochelia which
      histopathologically presented as noncaseating granulomas. The disease was
      progressive raising the suspicion of being oral manifestation of a systemic
      disorder such as Sarcoidosis or Crohn's disease. This paper throws some light on
      this rare entity and reports rarer features of this disease, like eye involvement
      and staphylococcal mucositis in the case report.

PMID- 29323073
TI  - Myoepithelial carcinoma of the tongue- spindle cell morphology with high mitosis:
      A case report and review of literature.
AB  - Myoepithelial carcinomas represent <1% of salivary gland tumors. Tongue is a rare
      site of occurrence. We present a case of a 30 year old female with myoepithelial
      carcinoma seen over dorsum of tongue with predominantly spindle cell morphology
      with clear cytoplasm and mitotic count of 6-7/10 hpf. We need to differentiate it
      from a spindle cell squamous cell carcinoma which can be seen at this location,
      i.e., tongue. In our case, there was no connection of the tumor with overlying
      squamous epithelium.

PMID- 29323074
TI  - Small cell medullary thyroid carcinoma: A diagnostic dilemma.
AB  - Small cell variant of medullary thyroid carcinoma (MTC) is a rare variant. In the
      past, primary thyroid lymphomas were thought to be small cell MTC (SCMTC).
      However, with the advent of immunohistochemistry, it was realized that SCMTC is
      rare. Our patient presented with neck mass for 1 year with an outside laboratory
      report of neoplastic lesion. His serum calcitonin levels were normal, but serum
      carcinoembryonic antigen (CEA) levels were high. He underwent total thyroidectomy
      and was diagnosed to have small cell variant of MTC. Immunohistochemistry for
      AE1/AE3 and CEA were positive while calcitonin was negative. The patient
      underwent radiotherapy but developed metastasis 3 months later. Thus, SCMTC is a
      rare and aggressive variant of MTC. In the absence of raised serum calcitonin
      levels, raised serum CEA levels are helpful. It is necessary to identify this
      rare variant as it connotes a poor prognosis and should be treated aggressively.

PMID- 29323075
TI  - Bilateral lung metastases unveils an asymptomatic sacrococcygeal yolk sac tumor.
AB  - Sacrococcygeal yolk sac tumor is an uncommon pediatric neoplasm. It usually
      presents with intra-abdominal or gluteal pain and mass. At later stage, it
      disseminates to regional nodes and distant organs. We describe one such neoplasm
      in an 18-month-old male child who turned symptomatic with multiple bilateral lung
      metastases. The tumor produced the least deformity to his physique, to become
      detectable on routine inspection and clinical examination. Finally, a combined
      approach through clinical, radiological, pathological, and biochemical
      perspectives established the diagnosis.

PMID- 29323076
TI  - Familial biatrial cardiac myxoma with glandular elements: A Rare entity with
      review of literature.
AB  - Cardiac myxomas are benign neoplasm of the heart with an incidence of 0.3%.
      Glandular cardiac myxomas are very rare and accounts for less than 3% of all
      cardiac myxomas. Here, we report a case of familial glandular cardiac myxoma in a
      35 year old male who complained of exertional dyspneoa and weakness of right side
      of body on clinical presentation. Associated features of Carney's complex were
      not present. Family history revealed presence of cardiac myxoma in younger
      brother and sister. Transthoracic echocardiography detected biatrial myxoma.
      Excision of both lesions was done under cardiopulmonary bypass. Histopathology
      confirmed myxoma with glandular elements. Postoperative course was uneventful.

PMID- 29323077
TI  - Epidermoid cyst of the renal pelvis masquerading as malignancy.
AB  - Epidermoid cyst of the renal pelvis is exceptionally rare. The histogenetic
      mechanism has not been well characterized. Herein, we report a case of intrarenal
      epidermoid cyst in a 62-year-old woman who had undergone left nephrolithotomy for
      a staghorn calculus. She was being followed up for bilateral renal cysts when a
      complex mass was noted arising from the lower pole of the left kidney. Renal
      ultrasound showed a small left kidney with a solid vascular echogenic mass. A
      laparoscopic radical nephrectomy was performed. Gross examination revealed a well
      circumscribed cystic mass with friable tan-yellow contents. Microscopically, a
      cystic structure lined by mature epidermis without atypia indicating epidermoid
      cyst was noted. The lesion appeared to be in continuity with the pelvicalyceal
      urothelium which displayed extensive squamous metaplasia. The patient is disease
      free and is doing well. Better clinical awareness of this benign entity and a
      preoperative biopsy may help preserve a kidney.

PMID- 29323078
TI  - Renal cell carcinoma with t(6,11): A case report and review of literature.
AB  - Renal cell carcinomas (RCCs) with t(6,11) are very rare tumours. Only a few cases
      have been reported so far. t(6,11) results in fusion of alpha gene and
      transcription factor EB (TFEB) gene resulting in the overexpression of TFEB. The
      specific light and immunohistochemical features help in the diagnosis of this
      rare type of tumor. We report a case of t(6,11) RCC in a 38-year-old female who
      was incidentally found to have a right renal mass. We present this case to
      emphasize the typical light microscopic picture of this extremely rare tumor. Two
      population of cells are seen: larger cells with abundant cytoplasm and smaller
      cells with scant cytoplasm. Smaller cells are arranged around hyaline nodules
      resulting in the formation of characteristic pseudorosettes.
      Immunohistochemically, these tumors are diffusely positive for vimentin and
      focally positive for HMB 45 and CD 117. Knowledge about the typical biphasic
      light microscopic appearance and the characteristic immunohistochemical features
      help in the diagnosis of this rare type of translocation associated RCC.

PMID- 29323079
TI  - Immunoglobulin G4-related tubulointerstitial nephritis: A not to be missed
      diagnosis.
AB  - Immunoglobulin G4-related tubulointerstitial nephritis (IgG4-TIN) is a newly
      recognized clinicopathological entity characterized by a dense interstitial
      infiltrate of IgG4-positive plasma cells accompanied by fibrosis and obliterative
      phlebitis causing acute or chronic renal dysfunction amenable to corticosteroid
      therapy. IgG4-TIN is the dominant manifestation of renal involvement in IgG4
      related disease (IgG4-RD) which is a novel, immune-mediated, fibroinflammatory
      and multiorgan disorder. We describe a case of IgG4-TIN with isolated renal
      involvement in an elderly male patient with poor response to corticosteroid
      therapy. The distinctive serological, histopathological, and ultrastructural
      features of this condition which can facilitate differential diagnosis of TIN are
      highlighted to emphasize the need for early diagnosis and preservation of kidney
      function.

PMID- 29323080
TI  - Recurrent leiomyosarcoma scrotum: An important differential in scrotal masses.
AB  - Soft tissue sarcomas of the genitourinary tract are rare. Paratesticular sarcomas
      are extremely rare with majority of scrotal masses localizing to the testis and
      being neoplastic in nature. Paratesticular leiomyosarcomas (LMSs) are located in
      the spermatic cord, epididymis, or scrotum. However, their location in the
      scrotal skin or subcutaneous tissue is extremely rare. Only 10 cases have been
      reported from India previously. Ours is the 11th case. A 50-year-old male
      presented with a recurrent scrotal mass which was painless and gradually
      increasing in size. Histopathology and immunohistochemistry confirmed it to be
      paratesticular LMS. A rare case report with the review of literature is
      presented.

PMID- 29323081
TI  - Primary signet cell adenocarcinoma of bladder.
AB  - Primary signet cell cancer of the urinary bladder is a relatively rare entity.
      Since there is no mucinous epithelium in the bladder, It is proposed that the
      tumor arises from metaplastic urothelium. Two thirds of the tumours are mucin
      secreting, in most of which the site of the deposition is either extracellular or
      intracellular displacing the nucleus to a peripheral crescent, giving the cells a
      signet ring appearance. The tumours are most often infiltrative and diffusely
      involving the majority of the bladder akin to its name sake in stomach. It is
      essential to distinguish this carcinoma from gastrointestinal metastases as
      different therapeutic strategies are often necessary.

PMID- 29323082
TI  - Pyogenic liver abscess associated with oral flora bacterium, Streptococcus
      anginosus in a patient with underlying tuberculosis.
AB  - Streptococcus anginosus forms a part of the commensal flora of the oral cavity.
      However, it can be aggressive and may lead to gastrointestinal and urogenital
      infections. We present an interesting case and course in a 38-year-old
      immunocompetent female patient with pyogenic liver abscess due to S. anginosus
      infection who had multiple carious teeth and underlying pulmonary tuberculosis.

PMID- 29323083
TI  - Monoclonal gammopathy with double M-bands: An atypical presentation on serum
      protein electrophoresis simulating biclonal gammopathy.
AB  - Monoclonal gammopathies, such as multiple myeloma, typically exhibit high levels
      of a monoclonal immunoglobulin (M-protein), produced by a clone of abnormally
      proliferating B-lymphocytes and/or plasma cells. The M-protein can be evaluated
      by serum protein electrophoresis (SPEP), which yields a single discrete band (M
      band), usually in the gamma-globulin region. Rarely, two M-bands appear
      simultaneously at different positions during SPEP - a condition known as biclonal
      gammopathy, which is a result of clonal expansion of two different neoplastic
      cell lines. Here, we describe an atypical case of IgA-lambda multiple myeloma,
      where double M-bands (one in beta- and the other in gamma-globulin region) were
      found during SPEP simulating biclonal gammopathy, although it was monoclonal in
      nature. This peculiar presentation of double M-bands in monoclonal gammopathy was
      attributed to polymeric forms of IgA by systematic workup. Further, we discuss
      how true and apparent biclonality can be distinguished by inexpensive analytical
      techniques in resource-constrained settings.

PMID- 29323084
TI  - Fibroblast growth factor receptor-1 associated myeloproliferative neoplasm and T
      lymphoblastic lymphoma.
AB  - Myeloid and lymphoid hematological malignancies with eosinophilia and
      abnormalities of fibroblast growth factor receptor-1 (FGFR1) result from the
      formation of abnormal fusion genes that encode constitutively activated tyrosine
      kinases. The WHO classification (2008) of hematolymphoid neoplasms recognizes a
      category of myeloid and lymphoid neoplasms with eosinophilia and abnormalities of
      FGFR1. Here, we present the case of a 30-year-old-woman who was diagnosed with T
      lymphoblastic lymphoma from lymph node biopsy and myeloproliferative neoplasm
      with eosinophilia from bone marrow studies. She was treated with combination
      chemotherapy with cyclophosphamide, vincristine, doxorubicin, and dexamethasone
      (Hyper-CVAD regimen) and is on maintenance chemotherapy for the past 2 months. We
      present this case to create awareness among physicians about this rare condition
      associated with dual malignancies.

PMID- 29323085
TI  - CD19-negative B-lineage acute lymphoblastic leukemia: A diagnostic and
      therapeutic challenge.
AB  - B-lineage acute lymphoblastic leukemia (B-ALL) is an aggressive neoplasm of B
      lymphocyte precursors that express the pan B-cell marker CD19 in all the cases.
      Rarely, a case may be assigned as B-lineage even if CD19 is negative. Here, a 16
      year-old male presented with complaints of pain abdomen, on and off fever, joint
      pain, and hepatosplenomegaly for 2 months. Bone marrow examination was suggestive
      of acute leukemia with numerous leukoblasts on aspiration. On flow cytometry,
      gated blast population was negative for CD19, cytoCD3, and myeloperoxidase MPO
      and positive for CD34, TdT, HLA-DR, CD22, CD79a, and CD10. Immunohistochemistry
      study showed positivity for TdT, CD34, CD10 (focal), and PAX 5 and negativity for
      CD20, CD3, MPO, CD117, and CD68. Lack of awareness of negative CD19 expression in
      B-ALL can lead to incorrect immunophenotypic diagnosis, treatment, and monitoring
      of B-ALL. Proper diagnosis should be based on clinical features, immunophenotypic
      profiles, immunohistochemistry findings, and molecular analysis.

PMID- 29323086
TI  - A rare case of Shewanella putrefaciens bacteremia in a patient of road traffic
      accident.
AB  - Shewanella putrefaciens rarely causes human infection. These are mostly found in
      environment and food stuffs. Shewanella are often found in mixed culture. It has
      been implicated in cellulitis, otitis media, and septicemia. It may be found in
      respiratory tract, urine, feces, and pleural fluid. There is no definite
      guideline for therapeutic option. In general, these are susceptible to various
      antimicrobial agents but are often resistant to penicillin and cephalothin. We
      report a rare case of bacteremia by S. putrefaciens in a patient of head injury
      with polytrauma after a road traffic accident.

PMID- 29323087
TI  - Opportunistic free: Living amoeba now becoming a usual pathogen?
AB  - Acanthamoeba species cause granulomatous Acanthamoeba encephalitis in
      immunocompromised patients. We report a case of acute purulent
      meningoencephalitis with a focal neurological deficit caused by Acanthamoeba
      species in a 2 years immunocompetent child.

PMID- 29323088
TI  - Salivary amylase crystalloids: An aspiration cytodiagnosis.

PMID- 29323089
TI  - Gliomatosis peritonei in mature cystic teratoma.

PMID- 29323090
TI  - Hepatic, splenic and thyroidal nodular sarcoidosis.

PMID- 29323091
TI  - Nerve sheath myxoma: Unusual location and a diagnostic pitfall.

PMID- 29323092
TI  - Addison's darling crisis.

PMID- 29323093
TI  - Urinary schistosomiasis: Schistosoma haematobium infection diagnosed by
      histopathology.

PMID- 29323094
TI  - Lepromatous leprosy-negative images giving the diagnostic clue.

PMID- 29323095
TI  - Intracytoplasmic inclusions in plasma cells: A diagnostic adjunct in monoclonal
      gammopathy of undetermined significance.

PMID- 29323096
TI  - Polypoid adenosarcoma of uterus with chondroid differentiation: A rare diagnosis.

PMID- 29323097
TI  - Balloon cell melanoma metastasis to the temporal lobe.

PMID- 29323098
TI  - An easy way of performing reticulocyte count by manual method.

PMID- 29323099
TI  - Leiomyosarcoma of parotid gland.

PMID- 29323100
TI  - Elizabethkingia meningoseptica peritonitis in continuous ambulatory peritoneal
      dialysis patient: A rare case report with diagnostic challenges.

PMID- 29323101
TI  - Actin Filament-Associated Protein 1-Like 1 Mediates Proliferation and Survival in
      Non-Small Cell Lung Cancer Cells.
AB  - BACKGROUND The actin filament-associated protein (AFAP) family consists of 3
      novel adaptor proteins: AFAP1, AFAP1L1, and AFAP1L2/XB130. Although evidence
      shows that AFAP1 and AFAP1L2 play an oncogenic role, the effect of AFAP1L1 on
      tumor cell behavior has not been fully elucidated, and it remains unknown whether
      AFAP1L1 could be a prognostic marker and/or therapeutic target of lung cancer.
      MATERIAL AND METHODS Human A549 non-small cell lung cancer (NSCLC) cells were
      used in this study. AFAP1L1 gene was knocked down by AFAP1L1 short hairpin RNA
      (shRNA) transfection. Cell proliferation was analyzed using Celigo image
      cytometry and MTT [3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium
      bromide] assay, cell cycle progression was assessed with flow cytometry, and cell
      apoptosis was determined by flow cytometry after annexin-n staining. The PathScan
      intracellular signaling array was used to investigate cancer-related signaling
      proteins influenced by knocking down AFAP1L1 in A549. RESULTS AFAP1L1 gene
      expression was successfully inhibited by the AFAP1L1-shRNA transfection. Cell
      proliferation was inhibited and cell proportions in G1 and G2/M phases were
      increased, and cell apoptosis was increased in the AFAP1L1-shRNA transfected
      cells as compared with negative control shRNA transfected cells. Using the
      PathScan intracellular signaling array, we found that downregulation of AFAP1L1
      significantly activated P38 and caspase 3, and inhibited PRAS40 activation.
      CONCLUSIONS Our data show that AFAP1L1 promotes cell proliferation, accelerates
      cell cycle progression, and prevents cell apoptosis in lung cancer cells.
      Therefore, AFAP1L1 might play an oncogenic role in NSCLC.

PMID- 29323102
TI  - Propionibacterium acnes induces intervertebral disc degeneration by promoting
      nucleus pulposus cell apoptosis via the TLR2/JNK/mitochondrial-mediated pathway.
AB  - Evidence suggests that intervertebral disc degeneration (IVDD) can be induced by
      Propionibacterium acnes (P. acnes), although the underlying mechanisms are
      unclear. In this study, we analyzed the pathological changes in degenerated human
      intervertebral discs (IVDs) infected with P. acnes. Compared with P. acnes
      negative samples, P. acnes-positive IVDs showed increased apoptosis of nucleus
      pulposus cells (NPCs) concomitant with severe IVDD. Then, a P. acnes-inoculated
      IVD animal model was established, and severe IVDD was induced by P. acnes
      infection by promoting NPC apoptosis. The results suggested that P.acnes-induced
      apoptosis of NPCs via the Toll-like receptor 2 (TLR2)/c-Jun N-terminal kinase
      (JNK) pathway and mitochondrial-mediated cell death. In addition, P. acnes was
      found to activate autophagy, which likely plays a role in apoptosis of NPCs.
      Overall, these findings further validated the involvement of P. acnes in the
      pathology of IVDD and provided evidence that P. acnes-induced apoptosis of NPCs
      via the TLR2/JNK pathway is likely responsible for the pathology of IVDD.

PMID- 29323103
TI  - Oridonin exerts anticancer effect on osteosarcoma by activating PPAR-gamma and
      inhibiting Nrf2 pathway.
AB  - Osteosarcoma is the most common high-grade human primary malignant bone sarcoma
      with lower survival in the past decades. Oridonin, a bioactive diterpenoid
      isolated from Rabdosia rubescens, has been proved to possess potent anti-cancer
      effects. However, its potential mechanism still remains not fully clear nowadays.
      In this study, we investigated the anticancer effect of oridonin on human
      osteosarcoma and illuminated the underlying mechanisms. In vitro, oridonin
      inhibited the cell viability of various osteosarcoma cells. We demonstrated that
      oridonin induced mitochondrial-mediated apoptosis by increasing Bax/Bcl-2 ratio,
      loss of mitochondrial membrane potential (MMP), triggering reactive oxygen
      species (ROS) generation and activating caspase-3 and caspase-9 cleavage in MG-63
      and HOS cells. Moreover, we found that oridonin triggered ROS by inhibiting NF-E2
      related factor 2 (Nrf2) pathway and induced mitochondrial apoptosis via
      inhibiting nuclear factor-kappaB (NF-kappaB) activation by activating Peroxisome
      Proliferator-Activated Receptor gamma (PPAR-gamma) in MG-63 and HOS cells. We
      further confirmed the results by PPAR-gamma inhibitor GW9662, PPAR-gamma siRNA as
      well as overexpression of PPAR-gamma and Nrf2 in vitro. Furthermore, our in vivo
      study showed that oridonin inhibited tumor growth with high safety via inducing
      apoptosis through activating PPAR-gamma and inhibiting Nrf2 activation in
      xenograft model inoculated HOS tumor. Taken together, oridonin exerted a dramatic
      pro-apoptotic effect by activating PPAR-gamma and inhibiting Nrf2 pathway in
      vitro and in vivo. Therefore, oridonin may be a promising and effective agent for
      human osteosarcoma in the future clinical applications.

PMID- 29323104
TI  - The mechanism of glycosphingolipid degradation revealed by a GALC-SapA complex
      structure.
AB  - Sphingolipids are essential components of cellular membranes and defects in their
      synthesis or degradation cause severe human diseases. The efficient degradation
      of sphingolipids in the lysosome requires lipid-binding saposin proteins and
      hydrolytic enzymes. The glycosphingolipid galactocerebroside is the primary lipid
      component of the myelin sheath and is degraded by the hydrolase beta
      galactocerebrosidase (GALC). This enzyme requires the saposin SapA for lipid
      processing and defects in either of these proteins causes a severe
      neurodegenerative disorder, Krabbe disease. Here we present the structure of a
      glycosphingolipid-processing complex, revealing how SapA and GALC form a
      heterotetramer with an open channel connecting the enzyme active site to the SapA
      hydrophobic cavity. This structure defines how a soluble hydrolase can cleave the
      polar glycosyl headgroups of these essential lipids from their hydrophobic
      ceramide tails. Furthermore, the molecular details of this interaction provide an
      illustration for how specificity of saposin binding to hydrolases is encoded.

PMID- 29323105
TI  - Enterovirus D68 virus-like particles expressed in Pichia pastoris potently induce
      neutralizing antibody responses and confer protection against lethal viral
      infection in mice.
AB  - Enterovirus D68 (EV-D68) has been increasingly associated with severe respiratory
      illness and neurological complications in children worldwide. However, no vaccine
      is currently available to prevent EV-D68 infection. In the present study, we
      investigated the possibility of developing a virus-like particle (VLP)-based EV
      D68 vaccine. We found that co-expression of the P1 precursor and 3CD protease of
      EV-D68 in Pichia pastoris yeast resulted in the generation of EV-D68 VLPs, which
      were composed of processed VP0, VP1, and VP3 capsid proteins and were visualized
      as ~30 nm spherical particles. Mice immunized with these VLPs produced serum
      antibodies capable of specifically neutralizing EV-D68 infections in vitro. The
      in vivo protective efficacy of the EV-D68 VLP candidate vaccine was assessed in
      two challenge experiments. The first challenge experiment showed that neonatal
      mice born to the VLP-immunized dams were fully protected from lethal EV-D68
      infection, whereas in the second experiment, passive transfer of anti-VLP sera
      was found to confer complete protection in the recipient mice. Collectively,
      these results demonstrate the proof-of-concept for VLP-based broadly effective EV
      D68 vaccines.

PMID- 29323106
TI  - Sequential forward and reverse transport of the Na+ Ca2+ exchanger generates Ca2+
      oscillations within mitochondria.
AB  - Mitochondrial Ca2+ homoeostasis regulates aerobic metabolism and cell survival.
      Ca2+ flux into mitochondria is mediated by the mitochondrial calcium uniporter
      (MCU) channel whereas Ca2+ export is often through an electrogenic Na+-Ca2+
      exchanger. Here, we report remarkable functional versatility in mitochondrial Na+
      Ca2+ exchange under conditions where mitochondria are depolarised. Following
      physiological stimulation of cell-surface receptors, mitochondrial Na+-Ca2+
      exchange initially operates in reverse mode, transporting cytosolic Ca2+ into the
      matrix. As matrix Ca2+ rises, the exchanger reverts to its forward mode state,
      extruding Ca2+. Transitions between reverse and forward modes generate repetitive
      oscillations in matrix Ca2+. We further show that reverse mode Na+-Ca2+ activity
      is regulated by the mitochondrial fusion protein mitofusin 2. Our results
      demonstrate that reversible switching between transport modes of an ion exchanger
      molecule generates functionally relevant oscillations in the levels of the
      universal Ca2+ messenger within an organelle.

PMID- 29323107
TI  - Serological survey of neutralizing antibodies to eight major enteroviruses among
      healthy population.
AB  - Human enteroviruses (EVs) are the most common causative agents infecting human,
      causing many harmful diseases, such as hand, foot, and mouth disease (HFMD),
      herpangina (HA), myocarditis, encephalitis, and aseptic meningitis. EV-related
      diseases pose a serious worldwide threat to public health. To gain comprehensive
      insight into the seroepidemiology of major prevalent EVs in humans, we firstly
      performed a serological survey for neutralizing antibodies (nAbs) against
      Enterovirus A71 (EV-A71), Coxsackie virus A16 (CV-A16), Coxsackie virus A6 (CV
      A6), Coxsackie virus A10 (CV-A10), Coxsackie virus B3 (CV-B3), Coxsackie virus B5
      (CV-B5), Echovirus 25 (ECHO25), and Echovirus 30 (ECHO30) among the healthy
      population in Xiamen City in 2016, using micro-neutralization assay. A total of
      515 subjects aged 5 months to 83 years were recruited by stratified random
      sampling. Most major human EVs are widely circulated in Xiamen City and usually
      infect infants and children. The overall seroprevalence of these eight EVs were
      ranged from 14.4% to 42.7%, and most of them increased with age and subsequently
      reached a plateau. The co-existence of nAbs against various EVs are common among
      people >= 7 years of age, due to the alternate infections or co-infections with
      different serotypes of EVs, while most children were negative for nAb against
      EVs, especially those < 1 year of age. This is the first report detailing the
      seroepidemiology of eight prevalent EVs in the same population, which provides
      scientific data supporting further studies on the improvement of EV-related
      disease prevention and control.

PMID- 29323108
TI  - Clinical study of tuberculosis in the head and neck region-11 years' experience
      and a review of the literature.
AB  - Tuberculosis (TB) is an infectious disease and major health concern. Head and
      neck tuberculosis (HNTB) is relatively rare, but can arise in many regions,
      including the lymph nodes, larynx, oral cavity and pharynx. We retrospectively
      reviewed the clinical records of 60 patients diagnosed with HNTB in our
      department between March 2005 and January 2016. A review and summary of previous
      HNTB articles published in PubMed since 1885 was also performed. The subjects
      consisted of 17 males and 43 females, and the average age of patients was 45 +/-
      14.67 years. The major clinical presentation was a lump or swelling, followed by
      an oral ulcer and skin fistula. The most common site of tuberculosis was in the
      cervical lymph node. Three patients also suffered from a malignant tumor in the
      head and neck region. A total of 980 papers involving 5881 patients were included
      in our literature review. The included subjects ranged in age from 15 months to
      100 years with a male-to-female ratio of 1.5:1. The larynx (38.92%), cervical
      lymph nodes (38.28%) and oral cavity (9.92%) were the three most common
      development sites. 465 patients were positive according to a HIV test, and 40
      patients had comorbidities with different types of tumors. Head and neck
      tuberculosis should always be considered during a differential diagnosis for
      lesions in the head and neck region. Early diagnosis and treatment can greatly
      enhance the therapeutic effect and patients' quality of life.

PMID- 29323109
TI  - Quantum engine efficiency bound beyond the second law of thermodynamics.
AB  - According to the second law, the efficiency of cyclic heat engines is limited by
      the Carnot bound that is attained by engines that operate between two thermal
      baths under the reversibility condition whereby the total entropy does not
      increase. Quantum engines operating between a thermal and a squeezed-thermal bath
      have been shown to surpass this bound. Yet, their maximum efficiency cannot be
      determined by the reversibility condition, which may yield an unachievable
      efficiency bound above unity. Here we identify the fraction of the exchanged
      energy between a quantum system and a bath that necessarily causes an entropy
      change and derive an inequality for this change. This inequality reveals an
      efficiency bound for quantum engines energised by a non-thermal bath. This bound
      does not imply reversibility, unless the two baths are thermal. It cannot be
      solely deduced from the laws of thermodynamics.

PMID- 29323111
TI  - Author Correction: Rationalizing the light-induced phase separation of mixed
      halide organic-inorganic perovskites.
AB  - The original version of this Article contained an error in the spelling of the
      author Joseph S. Manser, which was incorrectly given as Joseph M. Manser. This
      has now been corrected in both the PDF and HTML versions of the Article.

PMID- 29323110
TI  - Free choice shapes normalized value signals in medial orbitofrontal cortex.
AB  - Normalization is a common cortical computation widely observed in sensory
      perception, but its importance in perception of reward value and decision making
      remains largely unknown. We examined (1) whether normalized value signals occur
      in the orbitofrontal cortex (OFC) and (2) whether changes in behavioral task
      context influence the normalized representation of value. We record medial OFC
      (mOFC) single neuron activity in awake-behaving monkeys during a reward-guided
      lottery task. mOFC neurons signal the relative values of options via a divisive
      normalization function when animals freely choose between alternatives. The
      normalization model, however, performed poorly in a variant of the task where
      only one of the two possible choice options yields a reward and the other was
      certain not to yield a reward (so called: "forced choice"). The existence of such
      context-specific value normalization may suggest that the mOFC contributes
      valuation signals critical for economic decision making when meaningful
      alternative options are available.

PMID- 29323113
TI  - MXene molecular sieving membranes for highly efficient gas separation.
AB  - Molecular sieving membranes with sufficient and uniform nanochannels that break
      the permeability-selectivity trade-off are desirable for energy-efficient gas
      separation, and the arising two-dimensional (2D) materials provide new routes for
      membrane development. However, for 2D lamellar membranes, disordered interlayer
      nanochannels for mass transport are usually formed between randomly stacked
      neighboring nanosheets, which is obstructive for highly efficient separation.
      Therefore, manufacturing lamellar membranes with highly ordered nanochannel
      structures for fast and precise molecular sieving is still challenging. Here, we
      report on lamellar stacked MXene membranes with aligned and regular subnanometer
      channels, taking advantage of the abundant surface-terminating groups on the
      MXene nanosheets, which exhibit excellent gas separation performance with H2
      permeability >2200 Barrer and H2/CO2 selectivity >160, superior to the state-of
      the-art membranes. The results of molecular dynamics simulations quantitatively
      support the experiments, confirming the subnanometer interlayer spacing between
      the neighboring MXene nanosheets as molecular sieving channels for gas
      separation.

PMID- 29323112
TI  - Signaling ammonium across membranes through an ammonium sensor histidine kinase.
AB  - Sensing and uptake of external ammonium is essential for anaerobic ammonium
      oxidizing (anammox) bacteria, and is typically the domain of the ubiquitous
      Amt/Rh ammonium transporters. Here, we report on the structure and function of an
      ammonium sensor/transducer from the anammox bacterium "Candidatus Kuenenia
      stuttgartiensis" that combines a membrane-integral ammonium transporter domain
      with a fused histidine kinase. It contains a high-affinity ammonium binding site
      not present in assimilatory Amt proteins. The levels of phosphorylated histidine
      in the kinase are coupled to the presence of ammonium, as conformational changes
      during signal recognition by the Amt module are transduced internally to modulate
      the kinase activity. The structural analysis of this ammonium sensor by X-ray
      crystallography and small-angle X-ray-scattering reveals a flexible, bipartite
      system that recruits a large uptake transporter as a sensory module and modulates
      its functionality to achieve a mechanistic coupling to a kinase domain in order
      to trigger downstream signaling events.

PMID- 29323114
TI  - Publisher Correction: Causes of model dry and warm bias over central U.S. and
      impact on climate projections.
AB  - The original version of this Article contained an error in Figure 2. In panel a,
      the x axis of the graph was incorrectly labeled 'precipitation bias', and should
      have read 'negative precipitation bias'. This error has been corrected in both
      the PDF and HTML versions of the Article.

PMID- 29323115
TI  - Wet-dry cycles enable the parallel origin of canonical and non-canonical
      nucleosides by continuous synthesis.
AB  - The molecules of life were created by a continuous physicochemical process on an
      early Earth. In this hadean environment, chemical transformations were driven by
      fluctuations of the naturally given physical parameters established for example
      by wet-dry cycles. These conditions might have allowed for the formation of
      (self)-replicating RNA as the fundamental biopolymer during chemical evolution.
      The question of how a complex multistep chemical synthesis of RNA building blocks
      was possible in such an environment remains unanswered. Here we report that
      geothermal fields could provide the right setup for establishing wet-dry cycles
      that allow for the synthesis of RNA nucleosides by continuous synthesis. Our
      model provides both the canonical and many ubiquitous non-canonical purine
      nucleosides in parallel by simple changes of physical parameters such as
      temperature, pH and concentration. The data show that modified nucleosides were
      potentially formed as competitor molecules. They could in this sense be
      considered as molecular fossils.

PMID- 29323116
TI  - Impact on short-lived climate forcers increases projected warming due to
      deforestation.
AB  - The climate impact of deforestation depends on the relative strength of several
      biogeochemical and biogeophysical effects. In addition to affecting the exchange
      of carbon dioxide (CO2) and moisture with the atmosphere and surface albedo,
      vegetation emits biogenic volatile organic compounds (BVOCs) that alter the
      formation of short-lived climate forcers (SLCFs), which include aerosol, ozone
      and methane. Here we show that a scenario of complete global deforestation
      results in a net positive radiative forcing (RF; 0.12 W m-2) from SLCFs, with the
      negative RF from decreases in ozone and methane concentrations partially
      offsetting the positive aerosol RF. Combining RFs due to CO2, surface albedo and
      SLCFs suggests that global deforestation could cause 0.8 K warming after 100
      years, with SLCFs contributing 8% of the effect. However, deforestation as
      projected by the RCP8.5 scenario leads to zero net RF from SLCF, primarily due to
      nonlinearities in the aerosol indirect effect.

PMID- 29323118
TI  - Effects of crystallographic and geometric orientation on ion beam sputtering of
      gold nanorods.
AB  - Nanostructures may be exposed to irradiation during their manufacture, their
      engineering and whilst in-service. The consequences of such bombardment can be
      vastly different from those seen in the bulk. In this paper, we combine
      transmission electron microscopy with in situ ion irradiation with complementary
      computer modelling techniques to explore the physics governing the effects of 1.7
      MeV Au ions on gold nanorods. Phenomena surrounding the sputtering and associated
      morphological changes caused by the ion irradiation have been explored. In both
      the experiments and the simulations, large variations in the sputter yields from
      individual nanorods were observed. These sputter yields have been shown to
      correlate with the strength of channelling directions close to the direction in
      which the ion beam was incident. Craters decorated by ejecta blankets were found
      to form due to cluster emission thus explaining the high sputter yields.

PMID- 29323120
TI  - Solving the mystery of the yellow zone of the asthma action plan.

PMID- 29323119
TI  - CUG initiation and frameshifting enable production of dipeptide repeat proteins
      from ALS/FTD C9ORF72 transcripts.
AB  - Expansion of G4C2 repeats in the C9ORF72 gene is the most prevalent inherited
      form of amyotrophic lateral sclerosis and frontotemporal dementia. Expanded
      transcripts undergo repeat-associated non-AUG (RAN) translation producing
      dipeptide repeat proteins from all reading frames. We determined cis-factors and
      trans-factors influencing translation of the human C9ORF72 transcripts. G4C2
      translation operates through a 5'-3' cap-dependent scanning mechanism, requiring
      a CUG codon located upstream of the repeats and an initiator Met-tRNAMeti.
      Production of poly-GA, poly-GP, and poly-GR proteins from the three frames is
      influenced by mutation of the same CUG start codon supporting a frameshifting
      mechanism. RAN translation is also regulated by an upstream open reading frame
      (uORF) present in mis-spliced C9ORF72 transcripts. Inhibitors of the pre
      initiation ribosomal complex and RNA antisense oligonucleotides selectively
      targeting the 5'-flanking G4C2 sequence block ribosomal scanning and prevent
      translation. Finally, we identified an unexpected affinity of expanded
      transcripts for the ribosomal subunits independently from translation.

PMID- 29323117
TI  - Impaired autophagy bridges lysosomal storage disease and epithelial dysfunction
      in the kidney.
AB  - The endolysosomal system sustains the reabsorptive activity of specialized
      epithelial cells. Lysosomal storage diseases such as nephropathic cystinosis
      cause a major dysfunction of epithelial cells lining the kidney tubule, resulting
      in massive losses of vital solutes in the urine. The mechanisms linking lysosomal
      defects and epithelial dysfunction remain unknown, preventing the development of
      disease-modifying therapies. Here we demonstrate, by combining genetic and
      pharmacologic approaches, that lysosomal dysfunction in cystinosis results in
      defective autophagy-mediated clearance of damaged mitochondria. This promotes the
      generation of oxidative stress that stimulates Galpha12/Src-mediated
      phosphorylation of tight junction ZO-1 and triggers a signaling cascade involving
      ZO-1-associated Y-box factor ZONAB, which leads to cell proliferation and
      transport defects. Correction of the primary lysosomal defect, neutralization of
      mitochondrial oxidative stress, and blockage of tight junction-associated ZONAB
      signaling rescue the epithelial function. We suggest a link between defective
      lysosome-autophagy degradation pathways and epithelial dysfunction, providing new
      therapeutic perspectives for lysosomal storage disorders.

PMID- 29323121
TI  - The Endogenous GRP78 Interactome in Human Head and Neck Cancers: A Deterministic
      Role of Cell Surface GRP78 in Cancer Stemness.
AB  - Cell surface glucose regulated protein 78 (GRP78), an endoplasmic reticulum (ER)
      chaperone, was suggested to be a cancer stem cell marker, but the influence of
      this molecule on cancer stemness is poorly characterized. In this study, we
      developed a mass spectrometry platform to detect the endogenous interactome of
      GRP78 and investigated its role in cancer stemness. The interactome results
      showed that cell surface GRP78 associates with multiple molecules. The influence
      of cell population heterogeneity of head and neck cancer cell lines (OECM1, FaDu,
      and BM2) according to the cell surface expression levels of GRP78 and the GRP78
      interactome protein, Progranulin, was investigated. The four sorted cell groups
      exhibited distinct cell cycle distributions, asymmetric/symmetric cell divisions,
      and different relative expression levels of stemness markers. Our results
      demonstrate that cell surface GRP78 promotes cancer stemness, whereas drives
      cells toward a non-stemlike phenotype when it chaperones Progranulin. We conclude
      that cell surface GRP78 is a chaperone exerting a deterministic influence on
      cancer stemness.

PMID- 29323123
TI  - Publisher Correction: Imaging spectroscopy of solar radio burst fine structures.
AB  - The original version of this article contained errors in Refs 15, 27, 32, 33 and
      43, which were incorrectly given with the wrong journal name "Solid Phys." rather
      than the correct "Sol. Phys.". This has now been corrected in the PDF and HTML
      versions of the article.

PMID- 29323125
TI  - Author Correction: Hot carrier cooling mechanisms in halide perovskites.
AB  - The original version of this Article omitted an affiliation of Cheng Hon Alfred
      Huan: 'Institute of Materials Research and Engineering (IMRE), A*STAR, 2
      Fusionopolis Way, Innovis #08-03 138634, Singapore'.This has now been corrected
      in both the PDF and HTML versions of the article.

PMID- 29323124
TI  - MiR-770 suppresses the chemo-resistance and metastasis of triple negative breast
      cancer via direct targeting of STMN1.
AB  - Chemo-resistance and metastasis of triple negative breast cancer (TNBC)
      contributed the most of treatment failure in the clinic. MicroRNAs (miRNAs) have
      been proved to be involved in many biological processes and diseases. In this
      study, we aimed to determine the role of miR-770 in the regulation of chemo
      resistance and metastasis of TNBC. Clinically, miR-770 was highly expressed in
      chemo-sensitive tissues and predicted a better prognosis of TNBC. Functionally,
      ectopic expression of miR-770 suppressed the doxorubicin-resistance of TNBC cell
      lines via regulation of apoptosis and tumor microenvironment, which was mediated
      by exosomes. Moreover, miR-770 overexpression inhibited the migration and
      invasion. Rescue of STMN1 could partly reverse the effect of miR-770 in TNBC
      behaviors. Furthermore, we also demonstrated that overexpression of miR-770
      inhibited DOX resistance and metastasis in vivo. Taken together, our results
      proved that miR-770 could suppress the doxorubicin-resistance and metastasis of
      TNBC cells, which broaden our insights into the underlying mechanisms in chemo
      resistance and metastasis, and provided a new prognostic marker for TNBC cells.

PMID- 29323126
TI  - Discovery of superconductivity in quasicrystal.
AB  - Superconductivity is ubiquitous as evidenced by the observation in many crystals
      including carrier-doped oxides and diamond. Amorphous solids are no exception.
      However, it remains to be discovered in quasicrystals, in which atoms are ordered
      over long distances but not in a periodically repeating arrangement. Here we
      report electrical resistivity, magnetization, and specific-heat measurements of
      Al-Zn-Mg quasicrystal, presenting convincing evidence for the emergence of bulk
      superconductivity at a very low transition temperature of [Formula: see text] K.
      We also find superconductivity in its approximant crystals, structures that are
      periodic, but that are very similar to quasicrystals. These observations
      demonstrate that the effective interaction between electrons remains attractive
      under variation of the atomic arrangement from periodic to quasiperiodic one. The
      discovery of the superconducting quasicrystal, in which the fractal geometry
      interplays with superconductivity, opens the door to a new type of
      superconductivity, fractal superconductivity.

PMID- 29323122
TI  - Effect of rhythmic auditory cueing on parkinsonian gait: A systematic review and
      meta-analysis.
AB  - The use of rhythmic auditory cueing to enhance gait performance in parkinsonian
      patients' is an emerging area of interest. Different theories and underlying
      neurophysiological mechanisms have been suggested for ascertaining the
      enhancement in motor performance. However, a consensus as to its effects based on
      characteristics of effective stimuli, and training dosage is still not reached. A
      systematic review and meta-analysis was carried out to analyze the effects of
      different auditory feedbacks on gait and postural performance in patients
      affected by Parkinson's disease. Systematic identification of published
      literature was performed adhering to PRISMA guidelines, from inception until May
      2017, on online databases; Web of science, PEDro, EBSCO, MEDLINE, Cochrane,
      EMBASE and PROQUEST. Of 4204 records, 50 studies, involving 1892 participants met
      our inclusion criteria. The analysis revealed an overall positive effect on gait
      velocity, stride length, and a negative effect on cadence with application of
      auditory cueing. Neurophysiological mechanisms, training dosage, effects of
      higher information processing constraints, and use of cueing as an adjunct with
      medications are thoroughly discussed. This present review bridges the gaps in
      literature by suggesting application of rhythmic auditory cueing in conventional
      rehabilitation approaches to enhance motor performance and quality of life in the
      parkinsonian community.

PMID- 29323128
TI  - Majorana zero modes and long range edge correlation in interacting Kitaev chains:
      analytic solutions and density-matrix-renormalization-group study.
AB  - We study Kitaev model in one-dimension with open boundary condition by using
      exact analytic methods for non-interacting system at zero chemical potential as
      well as in the symmetric case of Delta = t, and by using density-matrix
      renormalization-group method for interacting system with nearest neighbor
      repulsion interaction. We suggest and examine an edge correlation function of
      Majorana fermions to characterize the long range order in the topological
      superconducting states and study the phase diagram of the interating Kitaev
      chain.

PMID- 29323127
TI  - Differential proteomics of lesional vs. non-lesional biopsies revealed non-immune
      mechanisms of alopecia areata.
AB  - Alopecia areata (AA) is one of the common hair disorders for which treatment is
      frequently ineffective and associated with relapsing episodes. Better
      understanding of disease mechanisms and novel therapeutic targets are thus
      required. From 10 AA patients, quantitative proteomics using LTQ-Orbitrap-XL mass
      spectrometer revealed 104 down-regulated, 4 absent, 3 up-regulated and 11 newly
      present proteins in lesional vs. non-lesional biopsies. Among these, the
      decreased levels of alpha-tubulin, vimentin, heat shock protein 70 (HSP70),
      HSP90, annexin A2 and alpha-enolase were successfully confirmed by Western
      blotting. Protein-protein interactions network analysis using STRING tool
      revealed that the most frequent biological processes/networks of the down
      regulated proteins included tissue development, cell differentiation, response to
      wounding and catabolic process, whereas those for the up-regulated proteins
      included biological process, metabolic process, cellular transport, cellular
      component organization and response to stimulus. Interestingly, only 5
      increased/newly present proteins were associated with the regulation of immune
      system, which may not be the predominant pathway in AA pathogenic mechanisms as
      previously assumed. In summary, we report herein the first proteome dataset of AA
      demonstrating a number of novel pathways, which can be linked to the disease
      mechanisms and may lead to discovery of new therapeutic targets for AA.

PMID- 29323129
TI  - Comparison of Adaptation between the Major Connectors Fabricated from Intraoral
      Digital Impressions and Extraoral Digital Impressions.
AB  - The objective was to compare the adaptation between the major connectors of
      removable partial dentures derived from intraoral digital impressions and
      extraoral digital impressions. Twenty-four volunteers were enrolled. Each
      volunteer received an intraoral digital impression and one extraoral digital
      impression digitized from conventional gypsum impression. A software was used to
      create the major connectors on digital impression datasets. After all the virtual
      major connectors designed from Group intraoral digital impressions (Group I) and
      Group extraoral digital impressions (Group E) were directly fabricated by 3D
      printing technique, the adaptation of the final major connectors in volunteers'
      mouths were measured. The adaptation ranged from 159.87 to 577.99 MUm in Group I
      while from 120.83 to 536.17 MUm in Group E. The adaptation of major connectors in
      Group I were found better at the midline palatine suture while the adaptation of
      major connectors in Group E were found better at the two sides of the palatal
      vault. In both groups, the highest accuracy in adaptation was revealed at the
      anterior margin of the major connectors. It is feasible to manufacture the major
      connectors by digital impression and 3D printing technique. Both the adaptation
      of the two kinds of digital impressions were clinical acceptable.

PMID- 29323131
TI  - Optimal swimming strategies and behavioral plasticity of oceanic whitetip sharks.
AB  - Animal behavior should optimize the difference between the energy they gain from
      prey and the energy they spend searching for prey. This is all the more critical
      for predators occupying the pelagic environment, as prey is sparse and patchily
      distributed. We theoretically derive two canonical swimming strategies for
      pelagic predators, that maximize their energy surplus while foraging. They
      predict that while searching, a pelagic predator should maintain small dive
      angles, swim at speeds near those that minimize the cost of transport, and
      maintain constant speed throughout the dive. Using biologging sensors, we show
      that oceanic whitetip shark (Carcharhinus longimanus) behavior matches these
      predictions. We estimate that daily energy requirements of an adult shark can be
      met by consuming approximately 1-1.5 kg of prey (1.5% body mass) per day; shark
      borne video footage shows a shark encountering potential prey numbers exceeding
      that amount. Oceanic whitetip sharks showed incredible plasticity in their
      behavioral strategies, ranging from short low-energy bursts on descents, to high
      speed vertical surface breaches from considerable depth. Oceanic whitetips live a
      life of energy speculation with minimization, very different to those of tunas
      and billfish.

PMID- 29323130
TI  - In vivo effect of opticin deficiency in cartilage in a surgically induced mouse
      model of osteoarthritis.
AB  - The SLRP opticin (OPTC) has been demonstrated to be produced and degraded in
      osteoarthritic (OA) human cartilage. Here, we investigated the in vivo effect of
      OPTC deficiency in OA cartilage. OA was induced in 10-week-old Optc -/- and Optc
      +/+ mice. Ten weeks post-surgery, cartilage was processed for histology and
      immunohistochemistry. SLRP expression was determined in non-operated mouse
      cartilage. OA Optc -/- demonstrated significant protection against cartilage
      degradation. Data revealed that in non-operated Optc -/- cartilage, expression of
      SLRPs lumican and epiphycan was up-regulated at day 3 and in 10-week-olds (p <=
      0.039), and fibromodulin down-regulated in 10-week-olds (p = 0.001).
      Immunohistochemistry of OA mice showed a similar pattern. In OA Optc -/-
      cartilage, markers of degradation and complement factors were all down-regulated
      (p <= 0.038). In OA Optc -/- cartilage, collagen fibers were thinner and better
      organized (p = 0.038) than in OA Optc +/+ cartilage. The protective effect of
      OPTC deficiency during OA results from an overexpression of lumican and
      epiphycan, known to bind and protect collagen fibers, and a decrease in
      fibromodulin, contributing to a reduction in the complement
      activation/inflammatory process. This work suggests that the evaluation of the
      composition of the different SLRPs in OA cartilage could be applied as a new tool
      for OA prognosis classification.

PMID- 29323132
TI  - Assembly of an atypical alpha-macroglobulin complex from Pseudomonas aeruginosa.
AB  - Alpha-2-macroglobulins (A2Ms) are large spectrum protease inhibitors that are
      major components of the eukaryotic immune system. Pathogenic and colonizing
      bacteria, such as the opportunistic pathogen Pseudomonas aeruginosa, also carry
      structural homologs of eukaryotic A2Ms. Two types of bacterial A2Ms have been
      identified: Type I, much like the eukaryotic form, displays a conserved thioester
      that is essential for protease targeting, and Type II, which lacks the thioester
      and to date has been poorly studied despite its ubiquitous presence in Gram
      negatives. Here we show that MagD, the Type II A2M from P. aeruginosa that is
      expressed within the six-gene mag operon, specifically traps a target protease
      despite the absence of the thioester motif, comforting its role in protease
      inhibition. In addition, analytical ultracentrifugation and small angle
      scattering show that MagD forms higher order complexes with proteins expressed in
      the same operon (MagA, MagB, and MagF), with MagB playing the key stabilization
      role. A P. aeruginosa strain lacking magB cannot stably maintain MagD in the
      bacterial periplasm, engendering complex disruption. This suggests a regulated
      mechanism of Mag complex formation and stabilization that is potentially common
      to numerous Gram-negative organisms, and that plays a role in periplasm
      protection from proteases during infection or colonization.

PMID- 29323133
TI  - The effect of image position on the Independent Components of natural binocular
      images.
AB  - Human visual performance degrades substantially as the angular distance from the
      fovea increases. This decrease in performance is found for both binocular and
      monocular vision. Although analysis of the statistics of natural images has
      provided significant insights into human visual processing, little research has
      focused on the statistical content of binocular images at eccentric angles. We
      applied Independent Component Analysis to rectangular image patches cut from
      locations within binocular images corresponding to different degrees of
      eccentricity. The distribution of components learned from the varying locations
      was examined to determine how these distributions varied across eccentricity. We
      found a general trend towards a broader spread of horizontal and vertical
      position disparity tunings in eccentric regions compared to the fovea, with the
      horizontal spread more pronounced than the vertical spread. Eccentric locations
      above the centroid show a strong bias towards far-tuned components, eccentric
      locations below the centroid show a strong bias towards near-tuned components.
      These distributions exhibit substantial similarities with physiological
      measurements in V1, however in common with previous research we also observe
      important differences, in particular distributions of binocular phase disparity
      which do not match physiology.

PMID- 29323134
TI  - Theoretical prediction of a charge-transfer phase transition.
AB  - Phase transition materials are attractive from the viewpoints of basic science as
      well as practical applications. For example, optical phase transition materials
      are used for optical recording media. If a phase transition in condensed matter
      could be predicted or designed prior to synthesizing, the development of phase
      transition materials will be accelerated. Herein we show a logical strategy for
      designing a phase transition accompanying a thermal hysteresis loop. Combining
      first-principles phonon mode calculations and statistical thermodynamic
      calculations considering cooperative interaction predicts a charge-transfer phase
      transition between the A-B and A+-B- phases. As an example, we demonstrate the
      charge-transfer phase transition on rubidium manganese hexacyanoferrate. The
      predicted phase transition temperature and the thermal hysteresis loop agree well
      with the experimental results. This approach will contribute to the rapid
      development of yet undiscovered phase transition materials.

PMID- 29323135
TI  - Peptide-based coatings for flexible implantable neural interfaces.
AB  - In the last decade, the use of flexible biosensors for neuroprosthetic and
      translational applications has widely increased. Among them, the polyimide (PI)
      based thin-film electrodes got a large popularity. However, the usability of
      these devices is still hampered by a non-optimal tissue-device interface that
      usually compromises the long-term quality of neural signals. Advanced strategies
      able to improve the surface properties of these devices have been developed in
      the recent past. Unfortunately, most of them are not easy to be developed and
      combined with micro-fabrication processes, and require long-term efforts to be
      testable with human subjects. Here we show the results of the design and in vitro
      testing of an easy-to-implement and potentially interesting coating approach for
      thin-film electrodes. In particular, two biocompatible coatings were obtained via
      covalent conjugation of a laminin-derived peptide, CAS-IKVAV-S (IKV), with
      polyimide sheets that we previously functionalized with vinyl- and amino- groups
      (PI_v and PI_a respectively). Both the engineered coatings (PI_v+IKV and
      PI_a+IKV) showed morphological and chemical properties able to support neuronal
      adhesion, neurite sprouting, and peripheral glial cell viability while reducing
      the fibroblasts contamination of the substrate. In particular, PI_v+IKV showed
      promising results that encourage further in vivo investigation and pave the way
      for a new generation of peptide-coated thin-film electrodes.

PMID- 29323136
TI  - Magnetically induced transparency of a quantum metamaterial composed of twin flux
      qubits.
AB  - Quantum theory is expected to govern the electromagnetic properties of a quantum
      metamaterial, an artificially fabricated medium composed of many quantum objects
      acting as artificial atoms. Propagation of electromagnetic waves through such a
      medium is accompanied by excitations of intrinsic quantum transitions within
      individual meta-atoms and modes corresponding to the interactions between them.
      Here we demonstrate an experiment in which an array of double-loop type
      superconducting flux qubits is embedded into a microwave transmission line. We
      observe that in a broad frequency range the transmission coefficient through the
      metamaterial periodically depends on externally applied magnetic field. Field
      controlled switching of the ground state of the meta-atoms induces a large
      suppression of the transmission. Moreover, the excitation of meta-atoms in the
      array leads to a large resonant enhancement of the transmission. We anticipate
      possible applications of the observed frequency-tunable transparency in
      superconducting quantum networks.

PMID- 29323137
TI  - Issues with the Specificity of Immunological Reagents for NLRP3: Implications for
      Age-related Macular Degeneration.
AB  - Contradictory data have been presented regarding the implication of the NACHT,
      LRR and PYD domains-containing protein 3 (NLRP3) inflammasome in age-related
      macular degeneration (AMD), the leading cause of vision loss in the Western
      world. Recognizing that antibody specificity may explain this discrepancy and in
      line with recent National Institutes of Health (NIH) guidelines requiring
      authentication of key biological resources, the specificity of anti-NLRP3
      antibodies was assessed to elucidate whether non-immune RPE cells express NLRP3.
      Using validated resources, NLRP3 was not detected in human primary or human
      established RPE cell lines under multiple inflammasome-priming conditions,
      including purported NLRP3 stimuli in RPE such as DICER1 deletion and Alu RNA
      transfection. Furthermore, NLRP3 was below detection limits in ex vivo macular
      RPE from AMD patients, as well as in human induced pluripotent stem cell (hiPSC)
      derived RPE from patients with overactive NLRP3 syndrome (Chronic infantile
      neurologic cutaneous and articulate, CINCA syndrome). Evidence presented in this
      study provides new data regarding the interpretation of published results
      reporting NLRP3 expression and upregulation in RPE and addresses the role that
      this inflammasome plays in AMD pathogenesis.

PMID- 29323138
TI  - Whole-Mount Adult Ear Skin Imaging Reveals Defective Neuro-Vascular Branching
      Morphogenesis in Obese and Type 2 Diabetic Mouse Models.
AB  - Obesity and type 2 diabetes are frequently associated with peripheral neuropathy.
      Though there are multiple methods for diagnosis and analysis of morphological
      changes of peripheral nerves and blood vessels, three-dimensional high-resolution
      imaging is necessary to appreciate the pathogenesis with an anatomically
      recognizable branching morphogenesis and patterning. Here we established a novel
      technique for whole-mount imaging of adult mouse ear skin to visualize branching
      morphogenesis and patterning of peripheral nerves and blood vessels. Whole-mount
      immunostaining of adult mouse ear skin showed that peripheral sensory and
      sympathetic nerves align with large-diameter blood vessels. Diet-induced obesity
      (DIO) mice exhibit defective vascular smooth muscle cells (VSMCs) coverage, while
      there is no significant change in the amount of peripheral nerves. The leptin
      receptor-deficient db/db mice, a severe obese and type 2 diabetic mouse model,
      exhibit defective VSMC coverage and a large increase in the amount of smaller
      diameter nerve bundles with myelin sheath and unmyelinated nerve fibers.
      Interestingly, an increase in the amount of myeloid immune cells was observed in
      the DIO but not db/db mouse skin. These data suggest that our whole-mount imaging
      method enables us to investigate the neuro-vascular and neuro-immune phenotypes
      in the animal models of obesity and diabetes.

PMID- 29323139
TI  - Reverse micelle Extraction of Antibiotics using an Eco-friendly Sophorolipids
      Biosurfactant.
AB  - Reverse micelles extraction of erythromycin and amoxicillin were carried out
      using the novel Sophorolipids biosurfactant. By replacing commonly used chemical
      surfactants with biosurfactant, reverse micelle extraction can be further
      improved in terms of environmental friendliness and sustainability. A central
      composite experimental design was used to investigate the effects of solution pH,
      KCl concentration, and sophorolipids concentration on the reverse micelle
      extraction of antibiotics. The most significant factor identified during the
      reverse micelle extraction of both antibiotics is the pH of aqueous solutions.
      Best forward extraction performance for erythromycin was found at feed phase pH
      of approximately 8.0 with low KCl and sophorolipids concentrations. Optimum
      recovery of erythromycin was obtained at stripping phase pH around 10.0 and with
      low KCl concentration. On the other hand, best forward extraction performance for
      amoxicillin was found at feed phase pH around 3.5 with low KCl concentration and
      high sophorolipids concentration. Optimum recovery of erythromycin was obtained
      at stripping phase pH around 6.0 with low KCl concentration. Both erythromycin
      and amoxicillin were found to be very sensitive toaqueous phase pH and can be
      easily degraded outside of their stable pH ranges.

PMID- 29323142
TI  - An application of machine learning to haematological diagnosis.
AB  - Quick and accurate medical diagnoses are crucial for the successful treatment of
      diseases. Using machine learning algorithms and based on laboratory blood test
      results, we have built two models to predict a haematologic disease. One
      predictive model used all the available blood test parameters and the other used
      only a reduced set that is usually measured upon patient admittance. Both models
      produced good results, obtaining prediction accuracies of 0.88 and 0.86 when
      considering the list of five most likely diseases and 0.59 and 0.57 when
      considering only the most likely disease. The models did not differ
      significantly, which indicates that a reduced set of parameters can represent a
      relevant "fingerprint" of a disease. This knowledge expands the model's utility
      for use by general practitioners and indicates that blood test results contain
      more information than physicians generally recognize. A clinical test showed that
      the accuracy of our predictive models was on par with that of haematology
      specialists. Our study is the first to show that a machine learning predictive
      model based on blood tests alone can be successfully applied to predict
      haematologic diseases. This result and could open up unprecedented possibilities
      for medical diagnosis.

PMID- 29323140
TI  - Loss of A20 in BM-MSCs regulates the Th17/Treg balance in Rheumatoid Arthritis.
AB  - Mesenchymal stem cells (MSCs) are multi-potent cells that are self-renewable and
      possess the potential to differentiate into multiple lineages. Several studies
      demonstrated that MSCs could regulate a Th17/Treg balance and could be a
      potential therapeutic target for Rheumatoid Arthritis (RA). A20 is highly
      expressed in many cell types after the stimulation of TNF-alpha, where it may
      inhibit pro-inflammatory cytokine secretion. However, the expression of A20 in BM
      MSCs in RA is not fully understood. In our study, we found that A20 was decreased
      in RA patients' bone marrow MSCs (BM-MSCs), and with more IL-6 secretion, the
      balance of Th17/Treg was broken. In CIA mice, we found a moderate A20 decrease in
      mice MSCs as compared with those of control group in mRNA and protein levels.
      However, the IL-6 expression was increased. After umbilical cord MSCs treatment,
      A20 and IL-6 expressions were equal to the control group. Thus, our study
      indicates that loss of A20 in MSCs regulates the Th17/Treg balance in RA and the
      regulatory role of A20 in pro-inflammatory IL-6 production could be a potential
      target for the transfer of MSCs in RA adoptive therapy.

PMID- 29323141
TI  - Comparison Long-term Outcome of Definitive Radiotherapy plus Different
      Chemotherapy Schedules in Patients with Advanced Nasopharyngeal Carcinoma.
AB  - Concurrent chemoradiotherapy (CCRT) is the current standard of care for advanced
      nasopharyngeal carcinoma (NPC). We hypothesize that shifting CCRT to neoadjuvant
      chemotherapy followed by radiotherapy (NeoCT-RT) is an alternative option. From
      December 2004 to January 2009, 256 NPC patients with stage II-IVB were treated by
      either CCRT or NeoCT-RT. All patients received the same dosage and fractionation
      schedule of RT. After long-term follow-up, 26.8% (34/127) and 23.3% (30/129) of
      patients who received CCRT and NeoCT-RT respectively, developed a tumor relapse
      (P = 0.6134). Overall survival (HR = 1.52, 95%CI = 0.91-2.55, P = 0.1532) and
      progression-free survival (HR = 1.22, 95%CI = 0.75-1.99, P = 0.4215) were similar
      in both groups. However, acute toxicities during RT period revealed a significant
      reduction of grade 3/4 vomiting (23% vs. 0%, P < 0.0001), mucositis (55% vs. 16%,
      P < 0.0001), and neck dermatitis (31% vs. 16%, P = 0.0041) in the NeoCT-RT group,
      resulting in fewer emergency room visits (10.2% vs. 1.6%, P = 0.0071). Severe
      treatment-related late toxicity (15% vs. 14%, P = 0.9590) and the occurrence of
      second malignancy (3.9% vs. 5.4%, P = 0.7887) also showed no differences. We
      concluded that NeoCT-RT could be an attractive alternative option of CCRT for
      advanced NPC.

PMID- 29323144
TI  - Defining tissue proteomes by systematic literature review.
AB  - Defining protein composition is a key step in understanding the function of both
      healthy and diseased biological systems. There is currently little consensus
      between existing published proteomes in tissues such as the aorta, cartilage and
      organs such as skin. Lack of agreement as to both the number and identity of
      proteins may be due to issues in protein extraction, sensitivity/specificity of
      detection and the use of disparate tissue/cell sources. Here, we developed a
      method combining bioinformatics and systematic review to screen >32M articles
      from the Web of Science for evidence of proteins in healthy human skin. The
      resulting Manchester Proteome ( www.manchesterproteome.manchester.ac.uk )
      collates existing evidence which characterises 2,948 skin proteins, 437 unique to
      our database and 2011 evidenced by both mass spectrometry and immune-based
      techniques. This approach circumvents the limitations of individual proteomics
      studies and can be applied to other species, organs, cells or disease-states.
      Accurate tissue proteomes will aid development of engineered constructs and offer
      insight into disease treatments by highlighting differences in proteomic
      composition.

PMID- 29323143
TI  - Optimizing human Treg immunotherapy by Treg subset selection and E-selectin
      ligand expression.
AB  - While human Tregs hold immense promise for immunotherapy, their biologic
      variability poses challenges for clinical use. Here, we examined clinically
      relevant activities of defined subsets of freshly-isolated and culture-expanded
      human PBMC-derived Tregs. Unlike highly suppressive but plastic memory Tregs
      (memTreg), naive Tregs (nvTreg) exhibited the greatest proliferation, suppressive
      capacity after stimulation, and Treg lineage fidelity. Yet, unlike memTregs,
      nvTregs lack Fucosyltransferase VII and display low sLeX expression, with
      concomitant poor homing capacity. In vitro nvTreg expansion augmented their
      suppressive function, but did not alter the nvTreg sLeX-l degrees w glycome.
      However, exofucosylation of the nvTreg surface yielded high sLeX expression,
      promoting endothelial adhesion and enhanced inhibition of xenogeneic aGVHD. These
      data indicate that the immature Treg glycome is under unique regulation and that
      adult PBMCs can be an ideal source of autologous-derived therapeutic Tregs,
      provided that subset selection and glycan engineering are engaged to optimize
      both their immunomodulation and tropism for inflammatory sites.

PMID- 29323145
TI  - Xyloglucan Fucosylation Modulates Arabidopsis Cell Wall Hemicellulose Aluminium
      binding Capacity.
AB  - Although xyloglucan (XyG) is reported to bind Aluminium (Al), the influence of
      XyG fucosylation on the cell wall Al binding capacity and plant Al stress
      responses is unclear. We show that Arabidopsis T-DNA insertion mutants with
      reduced AXY3 (XYLOSIDASE1) function and consequent reduced levels of fucosylated
      XyG are more sensitive to Al than wild-type Col-0 (WT). In contrast, T-DNA
      insertion mutants with reduced AXY8 (FUC95A) function and consequent increased
      levels of fucosylated XyG are more Al resistant. AXY3 transcript levels are
      strongly down regulated in response to 30 min Al treatment, whilst AXY8
      transcript levels also repressed until 6 h following treatment onset. Mutants
      lacking AXY3 or AXY8 function exhibit opposing effects on Al contents of root
      cell wall and cell wall hemicellulose components. However, there was no
      difference in the amount of Al retained in the pectin components between mutants
      and WT. Finally, whilst the total sugar content of the hemicellulose fraction did
      not change, the altered hemicellulose Al content of the mutants is shown to be a
      likely consequence of their different XyG fucosylation levels. We conclude that
      variation in XyG fucosylation levels influences the Al sensitivity of Arabidopsis
      by affecting the Al-binding capacity of hemicellulose.

PMID- 29323146
TI  - Ca2+-permeable mechanosensitive channels MCA1 and MCA2 mediate cold-induced
      cytosolic Ca2+ increase and cold tolerance in Arabidopsis.
AB  - Cold shock triggers an immediate rise in the cytosolic free calcium concentration
      ([Ca2+]cyt) in Arabidopsis thaliana and this cold-induced elevation of [Ca2+]cyt
      is inhibited by lanthanum or EGTA. It is suggested that intracellular calcium
      mainly contributes to the cold-induced [Ca2+]cyt response by entering into the
      cytosol. Two calcium-permeable mechanosensitive channels, MCA1 and MCA2 (mid1
      complementing activity), have been identified in Arabidopsis. Here, we
      demonstrate that MCA1 and MCA2 are involved in a cold-induced increase in
      [Ca2+]cyt. The cold-induced [Ca2+]cyt increase in mca1 and mca2 mutants was
      markedly lower than that in wild types. The mca1 mca2 double mutant exhibited
      chilling and freezing sensitivity, compared to wild-type plants. Expression of
      At5g61820, At3g51660, and At4g15490, which are not regulated by the CBF/DREB1s
      transcription factor, was down-regulated in mca1 mca2. These results suggest that
      MCA1 and MCA2 are involved in the cold-induced elevation of [Ca2+]cyt, cold
      tolerance, and CBF/DREB1-independent cold signaling.

PMID- 29323149
TI  - Winner-take-all in a phase oscillator system with adaptation.
AB  - We consider a system of generalized phase oscillators with a central element and
      radial connections. In contrast to conventional phase oscillators of the Kuramoto
      type, the dynamic variables in our system include not only the phase of each
      oscillator but also the natural frequency of the central oscillator, and the
      connection strengths from the peripheral oscillators to the central oscillator.
      With appropriate parameter values the system demonstrates winner-take-all
      behavior in terms of the competition between peripheral oscillators for the
      synchronization with the central oscillator. Conditions for the winner-take-all
      regime are derived for stationary and non-stationary types of system dynamics.
      Bifurcation analysis of the transition from stationary to non-stationary winner
      take-all dynamics is presented. A new bifurcation type called a Saddle Node on
      Invariant Torus (SNIT) bifurcation was observed and is described in detail.
      Computer simulations of the system allow an optimal choice of parameters for
      winner-take-all implementation.

PMID- 29323147
TI  - Laboratory Study on Disconnection Events in Comets.
AB  - When comets interacting with solar wind, straight and narrow plasma tails will be
      often formed. The most remarkable phenomenon of the plasma tails is the
      disconnection event, in which a plasma tail is uprooted from the comet's head and
      moves away from the comet. In this paper, the interaction process between a comet
      and solar wind is simulated by using a laser-driven plasma cloud to hit a
      cylinder obstacle. A disconnected plasma tail is observed behind the obstacle by
      optical shadowgraphy and interferometry. Our particle-in-cell simulations show
      that the difference in thermal velocity between ions and electrons induces an
      electrostatic field behind the obstacle. This field can lead to the convergence
      of ions to the central region, resulting in a disconnected plasma tail. This
      electrostatic-field-induced model may be a possible explanation for the
      disconnection events of cometary tails.

PMID- 29323150
TI  - Stratification-induced reorientation of disk settling through ambient density
      transition.
AB  - Settling due to gravity force is a basic transport mechanism of solid particles
      in fluids in the Earth. A large portion of particles occurring in nature and used
      in technical applications are non-spherical. Settling of particles is usually
      studied in homogeneous ambient conditions, however, stratification is inherent of
      natural fluids. It has been acknowledged that stratification modifies the
      velocity of settling spheres and amorphous aggregates. However, the effect of
      particle shape on the dynamics of settling through density-stratified ambient
      fluid has not been recognized well enough. Here I show experimental evidence that
      continuous density transition markedly modifies the settling dynamics of a disk
      in terms of settling velocity and orientation of a particle. Settling dynamics of
      a disk are more complex than dynamics of spheres and aggregates studied
      previously. I found that in a two-layer ambient with density transition, a disk
      settling in a low Reynolds number regime undergoes five phases of settling with
      the orientation varying from horizontal to vertical, and it may achieve two local
      minimum settling velocities in the density transition layer. Moreover, I found
      that the settling dynamics depends on a density difference between upper and
      lower homogeneous layers, stratification strength and thickness of density
      transition.

PMID- 29323148
TI  - Reference gene identification and validation for quantitative real-time PCR
      studies in developing Xenopus laevis.
AB  - Reference genes are essential for gene expression analysis when using real-time
      quantitative PCR (RT-qPCR). Xenopus laevis is a popular amphibian model for
      studying vertebrate embryogenesis and development. Further, X. laevis is ideal
      for studying thyroid signaling due to its thyroid dependent metamorphosis, a
      stage comparable to birth in humans. When using PCR based studies, a primary
      concern is the choice of reference genes. Commonly used references are eef1a1,
      odc1, rpl8, and actnB, although there is a lack of ad hoc reference genes for X.
      laevis. Here, we used previously published RNA-seq data on different X. laevis
      stages and identified the top 14 candidate genes with respect to their expression
      levels as a function of developmental stage and degree of variation. We further
      evaluated the stability of these and other candidate genes using RT-qPCR on
      various stages including the unfertilised eggs, whole embryos during early
      development and brains during late development. We used four different
      statistical software packages: deltaCT, geNorm, NormFinder and BestKeeper. We
      report optimized reference gene pair combinations for studying development (early
      whole embryos), brains at later stages (metamorphosis and adult), and  thyroid
      signalling. These reference gene pairs are suitable for studying different
      aspects of X. laevis development and organogenesis.

PMID- 29323151
TI  - Downregulation of Heat Shock Protein 70 Impairs Osteogenic and Chondrogenic
      Differentiation in Human Mesenchymal Stem Cells.
AB  - Human mesenchymal stem cells (hMSCs) show promise for bone and cartilage
      regeneration. Our previous studies demonstrated that hMSCs with periodic mild
      heating had enhanced osteogenic and chondrogenic differentiation with
      significantly upregulated heat shock protein 70 (HSP70). However, the role of
      HSP70 in adult tissue regeneration is not well studied. Here, we revealed an
      essential regulatory mechanism of HSP70 in osteogenesis and chondrogenesis using
      adult hMSCs stably transfected with specific shRNAs to knockdown HSP70. Periodic
      heating at 39  degrees C was applied to hMSCs for up to 26 days. HSP70 knockdown
      resulted in significant reductions of alkaline phosphatase activity, calcium
      deposition, and gene expression of Runx2 and Osterix during osteogenesis. In
      addition, knockdown of HSP70 led to significant decreases of collagens II and X
      during chondrogenesis. Thus, downregulation of HSP70 impaired hMSC osteogenic and
      chondrogenic differentiation as well as the enhancement of these processes by
      thermal treatment. Taken together, these findings suggest a putative mechanism of
      thermal-enhanced bone and cartilage formation and underscore the importance of
      HSP70 in adult bone and cartilage differentiation.

PMID- 29323152
TI  - Unravelling the effects of mechanical physiological conditioning on cardiac
      adipose tissue-derived progenitor cells in vitro and in silico.
AB  - Mechanical conditioning is incompletely characterized for stimulating therapeutic
      cells within the physiological range. We sought to unravel the mechanism of
      action underlying mechanical conditioning of adipose tissue-derived progenitor
      cells (ATDPCs), both in vitro and in silico. Cardiac ATDPCs, grown on 3 different
      patterned surfaces, were mechanically stretched for 7 days at 1 Hz. A custom
      designed, magnet-based, mechanical stimulator device was developed to apply ~10%
      mechanical stretching to monolayer cell cultures. Gene and protein analyses were
      performed for each cell type and condition. Cell supernatants were also collected
      to analyze secreted proteins and construct an artificial neural network. Gene and
      protein modulations were different for each surface pattern. After
      mechanostimulation, cardiac ATDPCs increased the expression of structural genes
      and there was a rising trend on cardiac transcription factors. Finally, secretome
      analyses revealed upregulation of proteins associated with both myocardial
      infarction and cardiac regeneration, such as regulators of the immune response,
      angiogenesis or cell adhesion. To conclude, mechanical conditioning of cardiac
      ATDPCs enhanced the expression of early and late cardiac genes in vitro.
      Additionally, in silico analyses of secreted proteins showed that mechanical
      stimulation of cardiac ATDPCs was highly associated with myocardial infarction
      and repair.

PMID- 29323153
TI  - Skeletal Characterization of the Fgfr3 Mouse Model of Achondroplasia Using Micro
      CT and MRI Volumetric Imaging.
AB  - Achondroplasia, the most common form of dwarfism, affects more than a quarter
      million people worldwide and remains an unmet medical need. Achondroplasia is
      caused by mutations in the fibroblast growth factor receptor 3 (FGFR3) gene which
      results in over-activation of the receptor, interfering with normal skeletal
      development leading to disproportional short stature. Multiple mouse models have
      been generated to study achondroplasia. The characterization of these preclinical
      models has been primarily done with 2D measurements. In this study, we explored
      the transgenic model expressing mouse Fgfr3 containing the achondroplasia
      mutation G380R under the Col2 promoter (Ach). Survival and growth rate of the Ach
      mice were reduced compared to wild-type (WT) littermates. Axial skeletal defects
      and abnormalities of the sternebrae and vertebrae were observed in the Ach mice.
      Further evaluation of the Ach mouse model was performed by developing 3D
      parameters from micro-computed tomography (micro-CT) and magnetic resonance
      imaging (MRI). The 3-week-old mice showed greater differences between the Ach and
      WT groups compared to the 6-week-old mice for all parameters. Deeper
      understanding of skeletal abnormalities of this model will help guide future
      studies for evaluating novel and effective therapeutic approaches for the
      treatment of achondroplasia.

PMID- 29323155
TI  - Canopy nitrogen distribution is optimized to prevent photoinhibition throughout
      the canopy during sun flecks.
AB  - As photoinhibition primarily reduces the photosynthetic light use efficiency at
      low light, sunfleck-induced photoinhibition might result in a fatal loss of
      carbon gain in the shade leaves within a canopy with barely positive carbon
      balance. We hypothesized that shade leaves at the lower canopy might retain a
      certain amount of leaf nitrogen (NL) to maintain energy consumption via electron
      transport, which contributes to circumventing photoinhibition during sunflecks to
      keep efficient utilization of low light during the rest period of daytime. We
      investigated excess energy production, a potential measure of susceptibility to
      photoinhibition, as a function of NL distribution within a Japanese oak canopy.
      Optimal NL distribution, which maximizes canopy carbon gain, may lead to a higher
      risk of photoinhibition in shade leaves during sunflecks. Conversely, uniform NL
      distribution would cause a higher risk of photoinhibition in sun leaves under the
      direct sunlight. Actual NL distribution equalized the risk of photoinhibition
      throughout the canopy indicated by the constant excess energy production at the
      highest light intensities that the leaves received. Such a homeostatic adjustment
      as a whole canopy concerning photoinhibition would be a key factor to explain why
      actual NL distribution does not maximize canopy carbon gain.

PMID- 29323154
TI  - Effects of metformin on colorectal cancer stem cells depend on alterations in
      glutamine metabolism.
AB  - Metformin has been known to suppress cancer stem cells (CSCs) in some cancers.
      However, the differential effects of metformin on CSCs and their mechanisms have
      not been reported. Herein, metformin induced pAMPK activation and pS6 suppression
      in metformin-sensitive (HT29) cells, but not in metformin-resistant (SW620)
      cells. The oxygen consumption rate was higher in HT29 cells than in SW620 cells
      and showed a prominent decrease after metformin treatment in HT29 cells. In
      glutamine-depleted medium, but not in low-glucose medium, SW620 cells became
      sensitive to the CSC-suppressing effect of metformin. A combination of metformin
      and glutaminase C inhibitor (compound 968) suppressed CSCs in SW620 cells and
      enhanced that effect in HT29 cells. SW620 cells showed higher expression of
      glutaminase 1 and glutamine transporter (ASCT2) than HT29 cells, especially ASCT2
      in CSCs. Knockdown of glutaminase 1, ASCT2, and c-Myc induced significant CSC
      suppression and enhanced CSC-suppressing effect of metformin and compound 968. In
      xenografts and human cancer organoids, combined treatment with metformin and
      compound 968 showed the same results as those shown in vitro. In conclusion, the
      effect of metformin on CSCs varies depending on the AMPK-mTOR and glutamine
      metabolism. The inhibition of glutamine pathway could enhance the CSC-suppressing
      effect of metformin, overcoming metformin resistance.

PMID- 29323156
TI  - Ischemia-induced Neuronal Cell Death Is Mediated by Chemokine Receptor CX3CR1.
AB  - The chemokine fractalkine (CX3CL1) and its receptor CX3CR1 play a fundamental
      role in the pathophysiology of stroke. Previous studies have focused on a
      paracrine interaction between neurons that produce fractalkine and microglia that
      express CX3CR1 receptors in the central nervous system. Recent findings have
      demonstrated the functional expression of CX3CR1 receptors by hippocampal
      neurons, suggesting their involvement in neuroprotective and neurodegenerative
      actions. To elucidate the roles of neuronal CX3CR1 in neurodegeneration induced
      by ischemic stroke, a mouse model of permanent middle cerebral artery occlusion
      (pMCAO) was employed. In the pMCAO mice, increased CX3CR1 levels, apoptosis
      associated morphological changes, and Caspase 3-positive neuronal cells were
      observed in the striatum and in the hippocampus 24 hours after occlusion.
      Upregulation of CX3CR1 in ischemic neurons is associated with neuronal apoptotic
      cell death. In contrast, ischemia-induced apoptotic neuronal cell death was
      decreased in CX3CR1 deficient mice. Cultured primary hippocampal neurons obtained
      from CX3CR1 deficient mice were more resistant to glutamate-induced
      excitotoxicity by blocking calcium influx than those from wild-type mice. For the
      first time, we reported that neuronal CXCR1 mediates neuronal apoptotic cell
      death in ischemia. Our results suggest that modulating CXCR1 activity offers a
      novel therapeutic strategy for stroke.

PMID- 29323157
TI  - Microwave measurement of giant unilamellar vesicles in aqueous solution.
AB  - A microwave technique is demonstrated to measure floating giant unilamellar
      vesicle (GUV) membranes in a 25 MUm wide and 18.8 MUm high microfluidic channel.
      The measurement is conducted at 2.7 and 7.9 GHz, at which a split-ring resonator
      (SRR) operates at odd modes. A 500 nm wide and 100 MUm long SRR split gap is used
      to scan GUVs that are slightly larger than 25 MUm in diameter. The smaller
      fluidic channel induces flattened GUV membrane sections, which make close contact
      with the SRR gap surface. The used GUVs are synthesized with POPC (16:0-18:1 PC 1
      palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine), SM (16:0 Egg Sphingomyelin) and
      cholesterol at different molecular compositions. It is shown that SM and POPC
      bilayers have different dielectric permittivity values, which also change with
      measurement frequencies. The obtained membrane permittivity values, e.g. 73.64
      j6.13 for POPC at 2.7 GHz, are more than 10 times larger than previously reported
      results. The discrepancy is likely due to the measurement of dielectric
      polarization parallel with, other than perpendicular to, the membrane surface.
      POPC and SM-rich GUV surface sections are also clearly identified. Further work
      is needed to verify the obtained large permittivity values and enable accurate
      analysis of membrane composition.

PMID- 29323158
TI  - Climate change risk to forests in China associated with warming.
AB  - Variations in forest net primary productivity (NPP) reflects the combined effects
      of key climate variables on ecosystem structure and function, especially on the
      carbon cycle. We performed risk analysis indicated by the magnitude of future
      negative anomalies in NPP in comparison with the natural interannual variability
      to investigate the impact of future climatic projections on forests in China.
      Results from the multi-model ensemble showed that climate change risk of
      decreases in forest NPP would be more significant in higher emission scenario in
      China. Under relatively low emission scenarios, the total area of risk was
      predicted to decline, while for RCP8.5, it was predicted to first decrease and
      then increase after the middle of 21st century. The rapid temperature increases
      predicted under the RCP8.5 scenario would be probably unfavorable for forest
      vegetation growth in the long term. High-level risk area was likely to increase
      except RCP2.6. The percentage area at high risk was predicted to increase from
      5.39% (2021-2050) to 27.62% (2071-2099) under RCP8.5. Climate change risk to
      forests was mostly concentrated in southern subtropical and tropical regions,
      generally significant under high emission scenario of RCP8.5, which was mainly
      attributed to the intensified dryness in south China.

PMID- 29323159
TI  - Temperature-induced surface reconstruction and interface structure evolution on
      ligament of nanoporous copper.
AB  - Micromorphology and atomic arrangement on ligament surface of nanoporous metals
      play a vital role in maintaining the structural stability, adjusting the reaction
      interface and endowing the functionality. Here we offer an instructive scientific
      understanding for temperature-induced surface reconstruction and interface
      structure evolution on ligament of nanoporous copper (NPC) based on
      systematically experimental observations and theoretical calculations. The
      results show that with dealloying temperature increasing, ligament surface
      micromorphology of NPC evolves from smooth to irregularity and to uniformly
      compressed semisphere, and finally to dispersed single-crystal nanoparticles
      accompanying with significant changes of interface structure from coherence to
      semi-coherence and to noncoherence. It can guide us to impart multifunctionality
      and enhanced reaction activity to porous materials just through surface self
      modification of homogeneous atoms rather than external invasion of heteroatoms
      that may bring about unexpected ill effects, such as shortened operation life
      owing to poisoning.

PMID- 29323160
TI  - Glutathione S-transferase (GST) of American Cockroach, Periplaneta americana:
      Classes, Isoforms, and Allergenicity.
AB  - Insect glutathione S-transferases (GSTs) play important roles in insecticide/drug
      resistance and stress response. Medically, GSTs of house dust mites
      (Dermatophagoides pteronyssinus and Blomia tropicalis) and German cockroach
      (Blattella germanica) are human allergens. In this study, classes, isoforms and B
      cell and allergenic epitopes of GST of American cockroach, Periplaneta americana,
      the predominant species in the tropics and subtropics were investigated for the
      first time. Enzymatically active native and recombinant P. americana-GSTs bound
      to IgE in sera of all P. americana allergic patients that were tested. By gel
      based proteomics and multiple sequence alignments, the native GST comprises three
      isoforms of delta and sigma classes. All isoforms interacted with serum IgE of
      the cockroach allergic subjects. Molecularly, the protein contains six B-cell
      epitopes; two epitopes located at beta1-alpha1 and beta4-alpha3 regions bound to
      patients' serum IgE, indicating that they are allergenic. P. americana are
      ubiquitous and their GST can sensitize humans to allergic diseases; thus, the
      protein should be included in the allergen array for component resolved diagnosis
      (CRD) of allergic patients, either by skin prick test or specific IgE
      determination. The GST is suitable also as a target of environmental allergen
      detection and quantification for intervention of cockroach sensitization and
      allergic morbidity.

PMID- 29323161
TI  - Lack of Fgf18 causes abnormal clustering of motor nerve terminals at the
      neuromuscular junction with reduced acetylcholine receptor clusters.
AB  - FGF receptor 2 is involved in the formation of the neuromuscular junction (NMJ),
      but its in vivo ligand remains to be determined. Laser capture microdissection of
      the mouse spinal motor neurons (SMNs) revealed that Fgf18 mRNA is highly
      expressed in SMNs in adults. Expression of Fgf18 mRNA was the highest in the
      spinal cord at embryonic day (E) 15.5, which gradually decreased to postnatal day
      7. FGF18 protein was localized at the NMJs of the tibialis anterior muscle at
      E18.5 and in adults. Fgf18-/- mice at E18.5 showed decreased expressions of the
      NMJ-specific Chrne and Colq genes in the diaphragm. In Fgf18-/- diaphragms, the
      synaptophysin-positive areas at the nerve terminals and the acetylcholine
      receptor (AChR)-positive areas at the motor endplates were both approximately one
      third of those in wild-type embryos. Fgf18-/- diaphragms ultrastructurally showed
      abnormal aggregation of multiple nerve terminals making a gigantic presynapse
      with sparse synaptic vesicles, and simplified motor endplates. In Fgf18-/-
      diaphragms, miniature endplate potentials were low in amplitude with markedly
      reduced frequency. In C2C12 myotubes, FGF18 enhanced AChR clustering, which was
      blocked by inhibiting FGFRs or MEK1. We propose that FGF18 plays a pivotal role
      in AChR clustering and NMJ formation in mouse embryogenesis.

PMID- 29323163
TI  - Carrier Dynamics and Electro-Optical Characterization of High-Performance
      GaN/InGaN Core-Shell Nanowire Light-Emitting Diodes.
AB  - In this work, we demonstrate high-performance electrically injected GaN/InGaN
      core-shell nanowire-based LEDs grown using selective-area epitaxy and
      characterize their electro-optical properties. To assess the quality of the
      quantum wells, we measure the internal quantum efficiency (IQE) using
      conventional low temperature/room temperature integrated photoluminescence. The
      quantum wells show a peak IQE of 62%, which is among the highest reported values
      for nanostructure-based LEDs. Time-resolved photoluminescence (TRPL) is also used
      to study the carrier dynamics and response times of the LEDs. TRPL measurements
      yield carrier lifetimes in the range of 1-2 ns at high excitation powers. To
      examine the electrical performance of the LEDs, current density-voltage (J-V) and
      light-current density-voltage (L-J-V) characteristics are measured. We also
      estimate the peak external quantum efficiency (EQE) to be 8.3% from a single side
      of the chip with no packaging. The LEDs have a turn-on voltage of 2.9 V and low
      series resistance. Based on FDTD simulations, the LEDs exhibit a relatively
      directional far-field emission pattern in the range of [Formula: see text]15
      degrees . This work demonstrates that it is feasible for electrically injected
      nanowire-based LEDs to achieve the performance levels needed for a variety of
      optical device applications.

PMID- 29323162
TI  - High co-expression of IL-34 and M-CSF correlates with tumor progression and poor
      survival in lung cancers.
AB  - Despite recent advances in diagnosis and treatment of lung cancers, the 5-year
      survival rate remains unsatisfactory, which necessitates the identification of
      novel factors that associates with disease progression and malignant degree for
      improving diagnostic and therapeutic strategies. Recent progress in cancer
      immunology research has unveiled critical roles for colony stimulating factor 1
      receptor (CSF1R) in multiple aspects of the tumor microenvironment. CSF1R is
      expressed on tumor-associated macrophages (TAMs), and mediates important pro
      tumorigenic functions. CSF1R also provides critical autocrine signals that
      promote cancer cell survival and proliferation. Activation of CSF1R can be
      achieved by two independent ligands; macrophage colony-stimulating factor (M-CSF)
      and interleukin 34 (IL-34). Accordingly, the expression of these ligands in
      cancer is expected to result in poor prognosis. In this study, we show that IL-34
      and M-CSF expression correlates with poor survival in a cohort of lung cancer
      patients. Importantly, high co-expression of IL-34 and M-CSF associates with the
      poorest survival compared to cancers that show weak or absent expression of the
      two ligands. Furthermore, high expression of IL-34 and M-CSF associates with
      advanced stages of lung cancers. Together, these results indicate a correlation
      between IL-34/M-CSF expression with poor survival and disease progression in lung
      cancer patients.

PMID- 29323164
TI  - Tailoring Lattice Strain and Ferroelectric Polarization of Epitaxial BaTiO3 Thin
      Films on Si(001).
AB  - Ferroelectric BaTiO3 films with large polarization have been integrated with
      Si(001) by pulsed laser deposition. High quality c-oriented epitaxial films are
      obtained in a substrate temperature range of about 300  degrees C wide. The
      deposition temperature critically affects the growth kinetics and thermodynamics
      balance, resulting on a high impact in the strain of the BaTiO3 polar axis, which
      can exceed 2% in films thicker than 100 nm. The ferroelectric polarization scales
      with the strain and therefore deposition temperature can be used as an efficient
      tool to tailor ferroelectric polarization. The developed strategy overcomes the
      main limitations of the conventional strain engineering methodologies based on
      substrate selection: it can be applied to films on specific substrates including
      Si(001) and perovskites, and it is not restricted to ultrathin films.

PMID- 29323165
TI  - Biotransformation and tissue distribution of protopine and allocryptopine and
      effects of Plume Poppy Total Alkaloid on liver drug-metabolizing enzymes.
AB  - In this study, the biotransformation in the plasma, urine and feces of rats
      following oral administration of protopine (PRO) and allocryptopine (ALL)were
      explored using HPLC-QqTOF MS. An HPLC-MS/MS method for the determination of
      tissues was developed and applied to the tissue distribution study in rats
      following intragastric administration of Plume Poppy Total Alkaloid for 3 weeks.
      A total of ten PRO metabolites and ten ALL metabolites were characterized in rats
      in vivo. Among these metabolites, six PRO metabolites and five ALL metabolites
      were reported for the first time. The predicated metabolic pathways including
      ring cleavage, demethylation following ring cleavage, and glucuronidation were
      proposed. The low-concentration residue of PRO and ALL in various tissues was
      detected at 24 h and 48 h after dosing, which indicated that both compounds could
      be widely distributed in tissues and exist as low levels of residue. The
      activities of erythromycin N-demethylase, aminopyrine N-demethylase and NAD (P)H
      quinone oxidoreductase in female rats can be induced post-dose, but these
      activities were inhibited in male rats. The proposed biotransformation and
      residues of PRO and ALL and their effects on enzymes may provide a basis for
      clarifying the metabolism and interpreting pharmacokinetics.

PMID- 29323166
TI  - Characterization of a new Pm2 allele associated with broad-spectrum powdery
      mildew resistance in wheat line Subtil.
AB  - Wheat powdery mildew is a severe disease affecting yield and quality. Host
      resistance was proved to be effective and environment-friendly. Wheat line Subtil
      is an elite germplasm resource resistant to 28 of 30 tested Bgt isolates. Genetic
      analysis showed that the powdery mildew resistance in Subtil was conferred by a
      single dominant gene, temporarily designated PmSub. Using bulked segregant
      analysis, PmSub was mapped to chromosome arm 5DS, and flanked by the markers
      Bwm16 and Cfd81/Bwm21 at 5.0 and 0.9 cM, respectively. Allelism tests further
      confirmed PmSub was allelic with documented Pm2 alleles. Then, homologous
      sequences of Pm2a related sequence was cloned from Subtil and Chinese Spring. It
      was completely identical to the reported Pm2a sequence, but significantly
      different from that of Chinese Spring. A marker SWGI067 was developed based on
      the sequence divergence of homologous sequence in Subtil and Chinese Spring.
      SWGI067 was closely linked to PmSub, indicating that the gene PmSub itself was
      different from the cloned Pm2a related sequence. Meanwhile, Subtil produced
      significantly different reaction pattern compared with other genotypes with Pm
      genes at or near Pm2 locus. Therefore, PmSub was most likely a new allele of Pm2.
      PmSub has opportunities for marker-assisted selecting for high-efficiency wheat
      improvement.

PMID- 29323167
TI  - Neural correlates of perceptual separation-induced enhancement of prepulse
      inhibition of startle in humans.
AB  - Prepulse inhibition (PPI) is the suppression of the startle reflex when the
      intense startling stimulus is shortly preceded by a weaker non-startling stimulus
      (prepulse). In rats, the auditory precedence-effect-induced perceived spatial
      separation between the fear-conditioned prepulse and a noise masker facilitates
      selective attention to the prepulse and enhances PPI. However, whether the
      perceptual separation between the prepulse and a noise masker can also enhance
      PPI in humans remains unclear. Also, the relationship between the PPI enhancement
      and the change in early cortical representations of prepulse signals is unclear.
      This study for the first time reveals that in a sound-attenuated laboratory
      environment, relative to the listening condition with perceptual co-location
      between the prepulse stimulus and a noise-masking stimulus, the perceptual
      separation between the two stimuli significantly enhances the group-mean PPI.
      More importantly, the early cortical responses (N1/P2 complex) to the prepulse
      stimulus are also enhanced by the perceptual separation in most listeners, and
      the perceptual-separation-induced enhancement of the N1 component is positively
      correlated with the perceptual-separation-induced PPI enhancement. Thus, the
      perceptual separation enhances PPI through facilitating selective attention to
      the prepulse, leading to an enhancement of the early cortical representation of
      the prepulse signal in temporal auditory cortical fields.

PMID- 29323169
TI  - Reconstruction of the domain orientation distribution function of polycrystalline
      PZT ceramics using vector piezoresponse force microscopy.
AB  - Lead zirconate titanate (PZT) is one of the prominent materials used in
      polycrystalline piezoelectric devices. Since the ferroelectric domain orientation
      is the most important parameter affecting the electromechanical performance,
      analyzing the domain orientation distribution is of great importance for the
      development and understanding of improved piezoceramic devices. Here, vector
      piezoresponse force microscopy (vector-PFM) has been applied in order to
      reconstruct the ferroelectric domain orientation distribution function of
      polished sections of device-ready polycrystalline lead zirconate titanate (PZT)
      material. A measurement procedure and a computer program based on the software
      Mathematica have been developed to automatically evaluate the vector-PFM data for
      reconstructing the domain orientation function. The method is tested on
      differently in-plane and out-of-plane poled PZT samples, and the results reveal
      the expected domain patterns and allow determination of the polarization
      orientation distribution function at high accuracy.

PMID- 29323168
TI  - Variations in bacterial and archaeal communities along depth profiles of Alaskan
      soil cores.
AB  - Understating the microbial communities and ecological processes that influence
      their structure in permafrost soils is crucial for predicting the consequences of
      climate change. In this study we investigated the bacterial and archaeal
      communities along depth profiles of four soil cores collected across Alaska. The
      bacterial and archaeal diversity (amplicon sequencing) overall decreased along
      the soil depth but the depth-wise pattern of their abundances (qPCR) varied by
      sites. The community structure of bacteria and archaea displayed site-specific
      pattern, with a greater role of soil geochemical characteristics rather than soil
      depth. In particular, we found significant positive correlations between methane
      trapped in cores and relative abundance of methanogenic archaeal genera,
      indicating a strong association between microbial activity and methane production
      in subsurface soils. We observed that bacterial phylogenetic community assembly
      tended to be more clustered in surface soils than in deeper soils. Analyses of
      phylogenetic community turnover among depth profiles across cores indicated that
      the relative influence of deterministic and stochastic processes was mainly
      determined by soil properties rather than depth. Overall, our findings emphasize
      that the vertical distributions of bacterial and archaeal communities in
      permafrost soils are to a large extent determined by the variation in site
      specific soil properties.

PMID- 29323171
TI  - New anti-inflammatory guaianes from the Atlantic hydrotherm-derived fungus
      Graphostroma sp. MCCC 3A00421.
AB  - Nine new guaianes (graphostromanes A-I, 1-9) were isolated from the deep-sea
      derived fungus Graphostroma sp. MCCC 3A00421, along with four known ones (10-13).
      The relative configurations were established mainly by detailed analysis of the
      NMR and HRESIMS data, while the absolute configurations were assigned using the X
      ray crystallography and modified Mosher's method. All isolates were evaluated for
      their inhibitory effects against lipopolysaccharide (LPS)-induced nitric oxide
      (NO) production in RAW264.7 macrophages. Graphostromanes F (6) showed remarkable
      inhibitory effect with an IC50 value of 14.2 MUM, which was even stronger than
      that of aminoguanidine, a positive control with an IC50 value of 23.4 MUM.

PMID- 29323170
TI  - Droplet digital PCR-based EGFR mutation detection with an internal quality
      control index to determine the quality of DNA.
AB  - In clinical translational research and molecular in vitro diagnostics, a major
      challenge in the detection of genetic mutations is overcoming artefactual results
      caused by the low-quality of formalin-fixed paraffin-embedded tissue (FFPET)
      derived DNA (FFPET-DNA). Here, we propose the use of an 'internal quality control
      (iQC) index' as a criterion for judging the minimum quality of DNA for PCR-based
      analyses. In a pre-clinical study comparing the results from droplet digital PCR
      based EGFR mutation test (ddEGFR test) and qPCR-based EGFR mutation test (cobas
      EGFR test), iQC index >= 0.5 (iQC copies >= 500, using 3.3 ng of FFPET-DNA [1,000
      genome equivalents]) was established, indicating that more than half of the input
      DNA was amplifiable. Using this criterion, we conducted a retrospective
      comparative clinical study of the ddEGFR and cobas EGFR tests for the detection
      of EGFR mutations in non-small cell lung cancer (NSCLC) FFPET-DNA samples.
      Compared with the cobas EGFR test, the ddEGFR test exhibited superior analytical
      performance and equivalent or higher clinical performance. Furthermore, iQC index
      is a reliable indicator of the quality of FFPET-DNA and could be used to prevent
      incorrect diagnoses arising from low-quality samples.

PMID- 29323172
TI  - Predictions through evidence accumulation over time.
AB  - It has been proposed that the brain specializes in predicting future states of
      the environment. These predictions are probabilistic, and must be continuously
      updated on the basis of their mismatch with actual evidence. Although
      electrophysiological data disclose neural activity patterns in relation to
      predictive processes, little is known about how this activity supports prediction
      build-up through evidence accumulation. Here we addressed this gap. Participants
      were required to make moment-by-moment predictions about stimuli presented in
      sequences in which gathering evidence from previous items as they were presented
      was either possible or not. Two event-related potentials (ERP), a frontocentral
      P2 and a central P3, were sensitive to information accumulation throughout the
      sequence. Time-frequency (TF) analyses revealed that prediction build-up process
      also modulated centrally distributed theta activity, and that alpha power was
      suppressed in anticipation to fully predictable stimuli. Results are in agreement
      with the notion of predictions as probability distributions and highlight the
      ability of observers to extract those probabilities in a changing environment and
      to adjust their predictions consequently.

PMID- 29323173
TI  - Electroporation of mice zygotes with dual guide RNA/Cas9 complexes for simple and
      efficient cloning-free genome editing.
AB  - In this report, we present an improved protocol for CRISPR/Cas9 genome editing in
      mice. The procedure consists in the electroporation of intact mouse zygotes with
      ribonucleoprotein complexes prepared in vitro from recombinant Cas9 nuclease and
      synthetic dual guide RNA. This simple cloning-free method proves to be extremely
      efficient for the generation of indels and small deletions by non-homologous end
      joining, and for the generation of specific point mutations by homology-directed
      repair. The procedure, which avoids DNA construction, in vitro transcription and
      oocyte microinjection, greatly simplifies genome editing in mice.

PMID- 29323174
TI  - Large-scale transcriptome changes in the process of long-term visual memory
      formation in the bumblebee, Bombus terrestris.
AB  - Many genes have been implicated in mechanisms of long-term memory formation, but
      there is still much to be learnt about how the genome dynamically responds,
      transcriptionally, during memory formation. In this study, we used high
      throughput sequencing to examine how transcriptome profiles change during visual
      memory formation in the bumblebee (Bombus terrestris). Expression of fifty-five
      genes changed immediately after bees were trained to associate reward with a
      single coloured chip, and the upregulated genes were predominantly genes known to
      be involved in signal transduction. Changes in the expression of eighty-one genes
      were observed four hours after learning a new colour, and the majority of these
      were upregulated and related to transcription and translation, which suggests
      that the building of new proteins may be the predominant activity four hours
      after training. Several of the genes identified in this study (e.g. Rab10, Shank1
      and Arhgap44) are interesting candidates for further investigation of the
      molecular mechanisms of long-term memory formation. Our data demonstrate the
      dynamic gene expression changes after associative colour learning and identify
      genes involved in each transcriptional wave, which will be useful for future
      studies of gene regulation in learning and long-term memory formation.

PMID- 29323176
TI  - Crystallization and Polymorphism of Organic Semiconductor in Thin Film Induced by
      Surface Segregated Monolayers.
AB  - Preparation of highly crystalline organic semiconductor films is vital to
      achieving high performance in electronic devices. Here we report that surface
      segregated monolayers (SSMs) on top of phenyl-C61-butyric acid methyl ester
      (PCBM) thin films induce crystal growth in the bulk, resulting in a dramatic
      change in the structure to form a new crystal phase. Highly ordered crystalline
      films with large domain sizes of several hundreds of nanometers are formed with
      uniaxial orientation of the crystal structure perpendicular to the substrate. The
      molecular rearrangements in SSMs trigger the nucleation at a lower temperature
      than that for the spontaneous nucleation in PCBM. The vertical charge mobility in
      the SSM-induced crystal domains of PCBM is five times higher than in the ordinary
      polycrystalline domains. Using surface monolayers may be a new strategy for
      controlling crystal structures and obtaining high-quality organic thin films by
      post-deposition crystallization.

PMID- 29323175
TI  - Functional Antibody Response Against V1V2 and V3 of HIV gp120 in the VAX003 and
      VAX004 Vaccine Trials.
AB  - Immunization with HIV AIDSVAX gp120 vaccines in the phase III VAX003 and VAX004
      trials did not confer protection. To understand the shortcomings in antibody (Ab)
      responses induced by these vaccines, we evaluated the kinetics of Ab responses to
      the V1V2 and V3 regions of gp120 and the induction of Ab-mediated antiviral
      functions during the course of 7 vaccinations over a 30.5-month period. Plasma
      samples from VAX003 and VAX004 vaccinees and placebo recipients were measured for
      ELISA-binding Abs and for virus neutralization, Ab-dependent cellular
      phagocytosis (ADCP), and Ab-dependent cellular cytotoxicity (ADCC). Ab responses
      to V1V2 and V3 peaked after 3 to 4 immunizations and declined after 5 to 7
      immunizations. The deteriorating responses were most evident against epitopes in
      the underside of the V1V2 beta-barrel and in the V3 crown. Correspondingly,
      vaccinees demonstrated higher neutralization against SF162 pseudovirus sensitive
      to anti-V1V2 and anti-V3 Abs after 3 or 4 immunizations than after 7
      immunizations. Higher levels of ADCP and ADCC were also observed at early or mid
      time points as compared with the final time point. Hence, VAX003 and VAX004
      vaccinees generated V1V2- and V3-binding Abs and functional Abs after 3 to 4
      immunizations, but subsequent boosts did not maintain these responses.

PMID- 29323177
TI  - Kirigami-based Elastic Metamaterials with Anisotropic Mass Density for
      Subwavelength Flexural Wave Control.
AB  - A novel design of an elastic metamaterial with anisotropic mass density is
      proposed to manipulate flexural waves at a subwavelength scale. The three
      dimensional metamaterial is inspired by kirigami, which can be easily
      manufactured by cutting and folding a thin metallic plate. By attaching the
      resonant kirigami structures periodically on the top of a host plate, a
      metamaterial plate can be constructed without any perforation that degrades the
      strength of the pristine plate. An analytical model is developed to understand
      the working mechanism of the proposed elastic metamaterial and the dispersion
      curves are calculated by using an extended plane wave expansion method. As a
      result, we verify an anisotropic effective mass density stemming from the
      coupling between the local resonance of the kirigami cells and the global
      flexural wave propagations in the host plate. Finally, numerical simulations on
      the directional flexural wave propagation in a two-dimensional array of kirigami
      metamaterial as well as super-resolution imaging through an elastic hyperlens are
      conducted to demonstrate the subwavelength-scale flexural wave control abilities.
      The proposed kirigami-based metamaterial has the advantages of no-perforation
      design and subwavelength flexural wave manipulation capability, which can be
      highly useful for engineering applications including non-destructive evaluations
      and structural health monitoring.

PMID- 29323178
TI  - MiR-152 Regulates Apoptosis and Triglyceride Production in MECs via Targeting
      ACAA2 and HSD17B12 Genes.
AB  - Mammary epithelial cells (MECs) affect milk production capacity during lactation
      and are critical for the maintenance of tissue homeostasis. Our previous studies
      have revealed that the expression of miR-152 was increased significantly in MECs
      of cows with high milk production. In the present study, bioinformatics analysis
      identified ACAA2 and HSD17B12 as the potential targets of miR-152, which were
      further validated by dual-luciferase repoter assay. In addition, the expressions
      of miR-152 was shown to be negatively correlated with levels of mRNA and protein
      of ACAA2, HSD17B12 genes by qPCR and western bot analysis. Furthermore,
      transfection with miR-152 significantly up-regulated triglyceride production,
      promoted proliferation and inhibited apoptosis in MECs. Furthermore,
      overexpression of ACAA2 and HSD17B12 could inhibit triglyceride production, cells
      proliferation and induce apoptosis; but sh234-ACAA2-181/sh234-HSD17B12-474 could
      reverse the trend. These findings suggested that miR-152 could significantly
      influence triglyceride production and suppress apoptosis, possibly via the
      expression of target genes ACAA2 and HSD17B12.

PMID- 29323179
TI  - Neither action nor phonological video games make dyslexic children read better.
AB  - The prevalence and long-term consequences of dyslexia make it crucial to look for
      effective and efficient ways of its therapy. Action video games (AVG) were
      implied as a possible remedy for difficulties in reading in Italian and English
      speaking children. However, the studies examining the effectiveness of AVG
      application in dyslexia suffered from significant methodological weaknesses such
      as small sample sizes and lack of a control group with no intervention. In our
      study, we tested how two forms of training: based on AVG and on phonological non
      action video games (PNAVG), affect reading in a group of fifty-four Polish
      children with dyslexia. Both speed and accuracy of reading increased in AVG as
      much as in PNAVG group. Moreover, both groups improved in phonological awareness,
      selective attention and rapid naming. Critically, the reading progress in the two
      groups did not differ from a dyslexic control group which did not participate in
      any training. Thus, the observed improvement in reading in AVG and PNAVG can be
      attributed either to the normal reading development related to schooling or to
      test practice effect. Overall, we failed to replicate previous studies: Neither
      AVG nor PNAVG remedy difficulties in reading in school children.

PMID- 29323180
TI  - Low amounts of dietary fibre increase in vitro production of short-chain fatty
      acids without changing human colonic microbiota structure.
AB  - This study investigated the effect of various prebiotics (indigestible dextrin,
      alpha-cyclodextrin, and dextran) on human colonic microbiota at a dosage
      corresponding to a daily intake of 6 g of prebiotics per person (0.2% of dietary
      intake). We used an in vitro human colonic microbiota model based on batch
      fermentation starting from a faecal inoculum. Bacterial 16S rRNA gene sequence
      analysis showed that addition of 0.2% prebiotics did not change the diversity and
      composition of colonic microbiota. This finding coincided with results from a
      clinical study showing that the microbiota composition of human faecal samples
      remained unchanged following administration of 6 g of prebiotics over seven days.
      However, compared to absence of prebiotics, their addition reduced the pH and
      increased the generation of acetate and propionate in the in vitro system. Thus,
      even at such relatively low amounts, prebiotics appear capable of activating the
      metabolism of colonic microbiota.

PMID- 29323182
TI  - Thickness Control of the Spin-Polarized Two-Dimensional Electron Gas in
      LaAlO3/BaTiO3 Superlattices.
AB  - We explored the possibility of increasing the interfacial carrier quantum
      confinement, mobility and conductivity in the (LaAlO3)n/(BaTiO3)n superlattices
      by thickness regulation using the first-principles electronic structure
      calculations. Through constructing two different interfacial types of
      LaAlO3/BaTiO3 superlattices, we discovered that the LaO/TiO2 interface is
      preferred from cleavage energy consideration. We then studied the electronic
      characteristics of two-dimensional electron gas (2DEG) produced at the LaO/TiO2
      interface in the LaAlO3/BaTiO3 superlattices via spin-polarized density
      functional theory calculations. The charge carrier density of 2DEG has a
      magnitude of 1014 cm-2 (larger than the traditional system LaAlO3/SrTiO3), which
      is mainly provided by the interfacial Ti 3dxy orbitals when the thicknesses of
      LaAlO3 and BaTiO3 layers are over 4.5 unit cells. We have also revealed the
      interfacial electronic characteristics of the LaAlO3/BaTiO3 system, by showing
      the completely spin-polarized 2DEG mostly confined at the superlattice interface.
      The interfacial charge carrier mobility and conductivity are found to be
      converged beyond the critical thickness. Therefore, we can regulate the
      interfacial confinement for the spin-polarized 2DEG and quantum transport
      properties in LaAlO3/BaTiO3 superlattice via controlling the thicknesses of the
      LaAlO3 and BaTiO3 layers.

PMID- 29323181
TI  - Oral exposure of low-dose bisphenol A promotes proliferation of dorsolateral
      prostate and induces epithelial-mesenchymal transition in aged rats.
AB  - Bisphenol A (BPA) is a well-known endocrine disruptor compound reported to have
      prostate toxicity. This study aimed to assess the effect of BPA on the
      proliferation of dorsolateral prostate (DLP) and the expression of epithelial
      mesenchymal transition (EMT)-related genes in aged rats. Male aged SD rats were
      treated with BPA (10.0, 30.0, and 90.0 ug/kg i.g., daily) or vehicle (i.g.,
      daily) for 3 months. Treatment with BPA resulted in increased the expression of
      PCNA, DLP weight and DLP epithelial height compared with the control group (P <
      0.01); such effects were more obvious at higher BPA doses. 90 ug/kg BPA
      significantly increased the estrogen to androgen ratio (P < 0.05). The EMT chip
      showed the BPA induced upregulation of vimentin, Snail, Twist1, and transforming
      growth factor beta 1, as well as the downregulation of E-cadherin in the DLP.
      Immunohistochemical data showed that the expression of vimentin, estrogen
      receptor subtypes, and androgen receptor increased and the expression of E
      cadherin decreased in 30 and 90 ug/kg BPA groups. It was concluded that
      environmental exposure to low doses of BPA might promote the proliferation of DLP
      in aged rats by increasing the estrogen to androgen ratio and inducing EMT.

PMID- 29323184
TI  - Microbial synthesis of a useful optically active (+)-isomer of lactone with
      bicyclo[4.3.0]nonane structure.
AB  - Lactone 2a of a bicyclo[4.3.0]nonane structure is a good starting material for
      synthesis of many attractive compounds. Enantiomerically enriched (-)-(3aR,7aS)
      lactone 2a is produced by whole cells of bacteria. In order to examine the impact
      of the absolute configuration on biological activity we evaluated the process
      affording the opposite isomer. To this purpose Candida pelliculosa ZP22
      characterized by high dehydrogenase activity was used. The goal of presented work
      was to perform bioreactor scale microbial one-pot oxidation of diol with selected
      yeast strain C. pelliculosa ZP22 to obtain chiral (+)-(3aS,7aR)-lactone 2a. The
      idea was to influence on alcohol dehydrogenase activity by increasing the
      activity of pro-(+)-ADH and simultanously diminishing the activity of pro-(-)
      ADH. The optimization of biotransformation conditions involved the manipulation
      of the nutritional and physical parameters. Selection of the optimal medium in
      order to improve yield and process enantioselectivity was based on a two-level
      factorial design methodology. We have also studied the relationship between
      microbial growth and biosynthesis of lactone 2a. Preparative oxidation of diol 3a
      (400 mg/L, 2.9 mM) catalyzed by C. pelliculosa ZP22 in an optimized conditions
      afforded enantiomerically enriched (+)-(3aS,7aR)-isomer of lactone 2a with the
      isolated yield (30%).

PMID- 29323183
TI  - Delivery of xenon-containing echogenic liposomes inhibits early brain injury
      following subarachnoid hemorrhage.
AB  - Xenon (Xe), a noble gas, has promising neuroprotective properties with no proven
      adverse side-effects. We evaluated neuroprotective effects of Xe delivered by Xe
      containing echogenic liposomes (Xe-ELIP) via ultrasound-controlled cerebral drug
      release on early brain injury following subarachnoid hemorrhage (SAH). The Xe
      ELIP structure was evaluated by ultrasound imaging, electron microscopy and gas
      chromatography-mass spectroscopy. Animals were randomly divided into five groups:
      Sham, SAH, SAH treated with Xe-ELIP, empty ELIP, or Xe-saturated saline.
      Treatments were administrated intravenously in combination with ultrasound
      application over the common carotid artery to trigger Xe release from circulating
      Xe-ELIP. Hematoma development was graded by SAH scaling and quantitated by a
      colorimetric method. Neurological evaluation and motor behavioral tests were
      conducted for three days following SAH injury. Ultrasound imaging and electron
      microscopy demonstrated that Xe-ELIP have a unique two-compartment structure,
      which allows a two-stage Xe release profile. Xe-ELIP treatment effectively
      reduced bleeding, improved general neurological function, and alleviated motor
      function damage in association with reduced apoptotic neuronal death and
      decreased mortality. Xe-ELIP alleviated early SAH brain injury by inhibiting
      neuronal death and bleeding. This novel approach provides a noninvasive strategy
      of therapeutic gas delivery for SAH treatment.

PMID- 29323185
TI  - Biogenesis of podosome rosettes through fission.
AB  - Podosomes are dynamic actin-based membrane protrusions that are important for
      extracellular matrix degradation and invasive cell motility. Individual podosomes
      are often found to organize into large rosette-like structures in some types of
      cells, such as osteoclasts, endothelial cells, Src-transformed fibroblasts, and
      certain highly invasive cancer cells. In this study, we show that new podosome
      rosettes arise through one of two mechanisms; de novo assembly or fission of a
      pre-existing podosome rosette in Src-transformed fibroblasts. Fission is a more
      efficient way than de novo assembly to generate new podosome rosettes in these
      cells. Podosome rosettes undergoing fission possess higher motility and a
      stronger matrix-degrading capability. Podosome rosette fission may be the result
      of polarized myosin II-mediated contractility of these structures, which is
      coordinately regulated by myosin light chain kinase and Rho-associated kinase II.
      Collectively, this study unveils a previously unknown mechanism-fission for the
      biogenesis of podosome rosettes.

PMID- 29323187
TI  - Strain effects on rotational property in nanoscale rotation system.
AB  - This paper presents a study of strain effects on nanoscale rotation system
      consists of double-walls carbon nanotube and graphene. It is found that the
      strain effects can be a real-time controlling method for nano actuator system.
      The strain effects on rotational property as well as the effect mechanism is
      studied systematically through molecular dynamics simulations, and it obtains
      valuable conclusions for engineering application of rotational property
      management of nanoscale rotation system. It founds that the strain effects tune
      the rotational property by influencing the intertube supporting effect and
      friction effect of double-walls carbon nanotube, which are two critical factors
      of rotational performance. The mechanism of strain effects on rotational property
      is investigated in theoretical level based on analytical model established
      through lattice dynamics theory. This work suggests great potentials of strain
      effects for nanoscale real-time control, and provides new ideas for design and
      application of real-time controllable nanoscale rotation system.

PMID- 29323186
TI  - Combination of high-fat/high-fructose diet and low-dose streptozotocin to model
      long-term type-2 diabetes complications.
AB  - The epidemic of type 2 diabetes mellitus (T2DM) is fueled by added fructose
      consumption. Here, we thus combined high-fat/high-fructose diet, with multiple
      low-dose injections of streptozotocin (HF/HF/Stz) to emulate the long-term
      complications of T2DM. HF/HF/Stz rats, monitored over 56 weeks, exhibited
      metabolic dysfunctions associated with the different stages of the T2DM disease
      progression in humans: an early prediabetic phase characterized by an
      hyperinsulinemic period with modest dysglycemia, followed by a late stage of T2DM
      with frank hyperglycemia, normalization of insulinemia, marked dyslipidemia,
      hepatic fibrosis and pancreatic beta-cell failure. Histopathological analyses
      combined to [18F]-FDG PET imaging further demonstrated the presence of several
      end-organ long-term complications, including reduction in myocardial glucose
      utilization, renal dysfunction as well as microvascular neuropathy and
      retinopathy. We also provide for the first time a comprehensive u-PET whole brain
      imaging of the changes in glucose metabolic activity within discrete cerebral
      regions in HF/HF/Stz diabetic rats. Altogether, we developed and characterized a
      unique non-genetic preclinical model of T2DM adapted to the current diet and
      lifestyle that recapitulates the major metabolic features of the disease
      progression, from insulin resistance to pancreatic beta-cell dysfunction, and
      closely mimicking the target-organ damage occurring in type 2 diabetic patients
      at advanced stages.

PMID- 29323188
TI  - A Tet-Off gene expression system for validation of antifungal drug targets in a
      murine invasive pulmonary aspergillosis model.
AB  - Aspergillus fumigatus is one of the major causes of invasive pulmonary
      aspergillosis in immunocompromised patients. Novel antifungal therapy is in
      urgent need due to emerging resistance and adverse toxicity of current antifungal
      drugs. Gene products that are essential for Aspergillus viability during
      infection are attractive drug targets. To characterize these genes in vivo we
      developed a Tet-Off gene expression system in A. fumigatus, whereby the
      administration of doxycycline resulted in down regulation of the gene whose
      expression is under the control of the Tet-Off promoter. We tested the system on
      two potential drug targets, inosine 5'-monophosphate dehydrogenase (IMPDH) and L
      ornithine N5-oxygenase (sidA) in a murine invasive pulmonary aspergillosis model.
      We show that depletion of IMPDH attenuated but did not completely abolish
      virulence in vivo whereas turning off the expression of sidA, which is required
      for iron acquisition, resulted in avirulence. We also investigated whether sidA
      expression could be controlled in a time-dependent manner in mice. Our results
      demonstrated that timing of doxycycline administration dramatically affects
      survival rate, suggesting that this genetic system can be used for testing
      whether an antifungal drug target is critical for fungal growth post-infection.

PMID- 29323189
TI  - IL-13 in LPS-Induced Inflammation Causes Bcl-2 Expression to Sustain Hyperplastic
      Mucous cells.
AB  - Exposure to lipopolysaccharides (LPS) causes extensive neutrophilic inflammation
      in the airways followed by mucous cell hyperplasia (MCH) that is sustained by the
      anti-apoptotic protein, Bcl-2. To identify inflammatory factor(s) that are
      responsible for Bcl-2 expression, we established an organ culture system
      consisting of airway epithelial tissue from the rat nasal midseptum. The highest
      Muc5AC and Bcl-2 expression was observed when organ cultures were treated with
      brochoalveolar lavage (BAL) fluid harvested from rats 10 h post LPS instillation.
      Further, because BAL harvested from rats depleted of polymorphonuclear cells
      compared to controls showed increased Bcl-2 expression, analyses of cytokine
      levels in lavages identified IL-13 as an inducer of Bcl-2 expression. Ectopic IL
      13 treatment of differentiated airway epithelial cells increased Bcl-2 and MUC5AC
      expression in the basal and apical regions of the cells, respectively. When Bcl-2
      was blocked using shRNA or a small molecule inhibitor, ABT-263, mucous cell
      numbers were reduced due to increased apoptosis that disrupted the interaction of
      Bcl-2 with the pro-apoptotic protein, Bik. Furthermore, intranasal instillation
      of ABT-263 reduced the LPS-induced MCH in bik +/+ but not bik -/- mice,
      suggesting that Bik mediated apoptosis in hyperplastic mucous cells. Therefore,
      blocking Bcl-2 function could be useful in reducing IL-13 induced mucous
      hypersecretion.

PMID- 29323191
TI  - Abnormally Low or High Ankle-Brachial Index Is Associated With the Development of
      Diabetic Retinopathy in Type 2 Diabetes Mellitus.
AB  - Although some studies have reported an association between peripheral artery
      disease (PAD) and diabetic retinopathy (DR) in patients with diabetes, whether or
      not a causal relationship exists is unknown. The aim of this study was to
      investigate whether PAD, as indicated by an abnormally low or high ankle-brachial
      index (ABI), is associated with the development of DR in patients with type 2
      diabetes mellitus (DM) without DR. We enrolled 414 (221 men and 193 women)
      patients with type 2 DM who underwent ABI measurements at our outpatient clinic.
      PAD was defined as an abnormally low (<0.9) or high (>=1.3) ABI in either leg,
      and DR was defined as being non-proliferative or proliferative. Of the enrolled
      patients, 69 (16.7%) had an ABI <0.9 or >=1.3. The median follow-up period was 23
      (15-40) months, during which 74 (17.9%) patients developed DR. In multivariate
      analysis, an ABI <0.9 or >=1.3 was independently associated with the development
      of DR (vs. ABI >=0.9 to <1.3; hazard ratio, 2.186; 95% confidence interval, 1.261
      to 3.789; p = 0.005). An abnormal ABI was associated with the development of DR
      in our patients with type 2 DM without DR.

PMID- 29323193
TI  - Rapid Thermal Processing to Enhance Steel Toughness.
AB  - Quenching and Tempering (Q&T) has been utilized for decades to alter steel
      mechanical properties, particularly strength and toughness. While tempering
      typically increases toughness, a well-established phenomenon called tempered
      martensite embrittlement (TME) is known to occur during conventional Q&T. Here we
      show that short-time, rapid tempering can overcome TME to produce unprecedented
      property combinations that cannot be attained by conventional Q&T. Toughness is
      enhanced over 43% at a strength level of 1.7 GPa and strength is improved over
      0.5 GPa at an impact toughness of 30 J. We also show that hardness and the
      tempering parameter (TP), developed by Holloman and Jaffe in 1945 and ubiquitous
      within the field, is insufficient for characterizing measured strengths,
      toughnesses, and microstructural conditions after rapid processing. Rapid
      tempering by energy-saving manufacturing processes like induction heating creates
      the opportunity for new Q&T steels for energy, defense, and transportation
      applications.

PMID- 29323190
TI  - Angiopoietins bind thrombomodulin and inhibit its function as a thrombin
      cofactor.
AB  - Angiopoietin-1 (Ang1) and Angiopoietin-2 (Ang2) are ligands for Tie2, an
      endothelial-specific receptor tyrosine kinase that is an essential regulator of
      angiogenesis. Here we report the identification, via expression cloning, of
      thrombomodulin (TM) as another receptor for Ang1 and Ang2. Thrombomodulin is an
      endothelial cell surface molecule that plays an essential role as a coagulation
      inhibitor via its function as a cofactor in the thrombin-mediated activation of
      protein C, an anticoagulant protein, as well as thrombin-activatable fibrinolysis
      inhibitor (TAFI). Ang1 and Ang2 inhibited the thrombin/TM-mediated generation of
      activated protein C and TAFI in cultured endothelial cells, and inhibited the
      binding of thrombin to TM in vitro. Ang2 appears to bind TM with higher affinity
      than Ang1 and is a more potent inhibitor of TM function. Consistent with a
      potential role for angiopoietins in coagulation, administration of thrombin to
      mice rapidly increased plasma Ang1 levels, presumably reflecting release from
      activated platelets (previously shown to contain high levels of Ang1). In
      addition, Ang1 levels were significantly elevated in plasma prepared from wound
      blood, suggesting that Ang1 is released from activated platelets at sites of
      vessel injury. Our results imply a previously undescribed role for angiopoietins
      in the regulation of hemostasis.

PMID- 29323192
TI  - Baseline IL-2 and the AIH score can predict the response to standard therapy in
      paediatric autoimmune hepatitis.
AB  - Although autoimmune hepatitis (AIH) can be treated with corticosteroid-based
      first-line therapy, incomplete remission is associated with progressive liver
      fibrosis. So far accepted predictors of the subsequent treatment response of AIH
      patients are lacking. Therefore, we analysed baseline parameters, including iron
      homeostasis and cytokine levels, in 60 children with paediatric AIH (pAIH). In
      contrast to adults, elevated serum markers indicating iron overload were not
      commonly found in children. Therefore, ferritin was not predictive of the
      treatment response in pAIH. Although baseline immunoglobulins were lower in pAIH
      children with subsequent complete biochemical remission (BR) upon standard first
      line therapy, only lower AIH scores (<=16 points) could predict BR upon standard
      therapy in our training and validation cohorts. Additionally, higher baseline IL
      2 and MCP-1/CCL2 levels were associated with BR in a sub-cohort. A combined score
      of IL-2 level and a simplified AIH score predicted treatment response more
      precisely than both parameter alone in this sub-cohort. In conclusion, the
      baseline AIH score could be validated as a predictor of treatment response in
      pAIH. Additionally, low baseline IL-2 may help identify children who need salvage
      therapy. This could be important because the use of low-dose IL-2 therapies is
      being tested in various autoimmune diseases.

PMID- 29323195
TI  - Gastropod shell size and architecture influence the applicability of methods used
      to estimate internal volume.
AB  - Obtaining accurate and reproducible estimates of internal shell volume is a vital
      requirement for studies into the ecology of a range of shell-occupying organisms,
      including hermit crabs. Shell internal volume is usually estimated by filling the
      shell cavity with water or sand, however, there has been no systematic assessment
      of the reliability of these methods and moreover no comparison with modern
      alternatives, e.g., computed tomography (CT). This study undertakes the first
      assessment of the measurement reproducibility of three contrasting approaches
      across a spectrum of shell architectures and sizes. While our results suggested a
      certain level of variability inherent for all methods, we conclude that a single
      measure using sand/water is likely to be sufficient for the majority of studies.
      However, care must be taken as precision may decline with increasing shell size
      and structural complexity. CT provided less variation between repeat measures but
      volume estimates were consistently lower compared to sand/water and will need
      methodological improvements before it can be used as an alternative. CT indicated
      volume may be also underestimated using sand/water due to the presence of air
      spaces visible in filled shells scanned by CT. Lastly, we encourage authors to
      clearly describe how volume estimates were obtained.

PMID- 29323194
TI  - Human Mesenchymal Stromal Cell-Derived Extracellular Vesicles Modify Microglial
      Response and Improve Clinical Outcomes in Experimental Spinal Cord Injury.
AB  - No current clinical intervention can alter the course of acute spinal cord injury
      (SCI), or appreciably improve neurological outcome. Mesenchymal stromal cells
      (MSCs) have been shown to modulate the injury sequelae of SCI largely via
      paracrine effects, although the mechanisms remain incompletely understood. One
      potential modality is through secretion of extracellular vesicles (EVs). In this
      study, we investigate whether systemic administration of EVs isolated from human
      MSCs (MSCEv) has the potential to be efficacious as an alternative to cell-based
      therapy for SCI. Additionally, we investigate whether EVs isolated from human
      MSCs stimulated with pro-inflammatory cytokines have enhanced anti-inflammatory
      effects when administered after SCI. Immunohistochemistry supported the
      quantitative analysis, demonstrating a diminished inflammatory response with
      apparent astrocyte and microglia disorganization in cord tissue up to 10 mm
      caudal to the injury site. Locomotor recovery scores showed significant
      improvement among animals treated with MSCEv. Significant increases in mechanical
      sensitivity threshold were observed in animals treated with EVs from either naive
      MSC (MSCEvwt) or stimulated MSC (MSCEv+), with a statistically significant
      increase in threshold for MSCEv+-treated animals when compared to those that
      received MSCEvwt. In conclusion, these data show that treatment of acute SCI with
      extracellular vesicles derived from human MSCs attenuates neuroinflammation and
      improves functional recovery.

PMID- 29323196
TI  - The Rotation of Microrobot Simplifies 3D Control Inside Microchannels.
AB  - This paper focuses on the control of rotating helical microrobots inside
      microchannels. We first use a 50 MUm long and 5 MUm in diameter helical robot to
      prove that the proximity of the channel walls create a perpendicular force on the
      robot. This force makes the robot orbit around the channel center line. We also
      demonstrate experimentally that this phenomenon simplifies the robot control by
      guiding it on a channel even if the robot propulsion is not perfectly aligned
      with the channel direction. We then use numerical simulations, validated by real
      experimental cases, to show different implications on the microrobot control of
      this orbiting phenomenon. First, the robot can be centered in 3D inside an in
      plane microchannel only by controlling its horizontal direction (yaw angle). This
      means that a rotating microrobot can be precisely controlled along the center of
      a microfluidic channel only by using a standard 2D microscopy technology. Second,
      the robot horizontal (yaw) and vertical (pitch) directions can be controlled to
      follow a 3D evolving channel only with a 2D feedback. We believe this could lead
      to simplify imaging systems for the potential in vivo integration of such
      microrobots.

PMID- 29323197
TI  - Outcomes of ureteroscopy miniaturization on tissue damage and tissue hypoxia in a
      pig model.
AB  - Miniaturization of ureteroscopy materials is intended to decrease tissue damage.
      However, tissue hypoxia and the gross and microscopic effects on tissue have not
      been adequately assessed. We compared the gross and microscopic effects of micro
      ureteroscopy (m-URS) and conventional ureteroscopy (URS) on the urinary tract. We
      employed 14 pigs of the Large White race. URS was performed in one of the ureters
      with an 8/9.8 F ureteroscope, while a 4.85 F m-URS sheath was used in the
      contralateral ureter. Gross assessment of ureteral wall damage and ureteral
      orifice damage was performed. For microscopic assessment hematoxylin-eosin
      staining and immunohistochemistry for detection of tissue hypoxia were conducted.
      Regarding the macroscopic assessment of ureteral damage, substantial and
      significant differences were recorded using URS (C = 0.8), but not with m-URS.
      Microscopic assessment after staining with hematoxylin-eosin revealed greater
      epithelial desquamation in the URS group (p < 0.05). Pimonidazole staining
      revealed greater hypoxia in the epithelial cells than in the remainder of the
      ureteral layers. We conclude that m-URS causes less damage to the ureteral
      orifice than URS. Histopathological findings show m-URS reduces ureteral
      epithelial damage compared with conventional ureteroscopy. Both URS and m-URS
      cause cellular hypoxia.

PMID- 29323199
TI  - Observation of carrier localization in cubic crystalline Ge2Sb2Te5 by field
      effect measurement.
AB  - The tunable disorder of vacancies upon annealing is an important character of
      crystalline phase-change material Ge2Sb2Te5 (GST). A variety of resistance states
      caused by different degrees of disorder can lead to the development of multilevel
      memory devices, which could bring a revolution to the memory industry by
      significantly increasing the storage density and inspiring the neuromorphic
      computing. This work focuses on the study of disorder-induced carrier
      localization which could result in multiple resistance levels of crystalline GST.
      To analyze the effect of carrier localization on multiple resistant levels, the
      intrinsic field effect (the change in surface conductance with an applied
      transverse electric field) of crystalline GST was measured, in which GST films
      were annealed at different temperatures. The field effect measurement is an
      important complement to conventional transport measurement techniques. The field
      effect mobility was acquired and showed temperature activation, a hallmark of
      carrier localization. Based on the relationship between field effect mobility and
      annealing temperature, we demonstrate that the annealing shifts the mobility edge
      towards the valence-band edge, delocalizing more carriers. The insight of carrier
      transport in multilevel crystalline states is of fundamental relevance for the
      development of multilevel phase change data storage.

PMID- 29323198
TI  - Paroxysmal Nocturnal Hemoglobinuria (Pnh): Brain Mri Ischemic Lesions In
      Neurologically Asymtomatic Patients.
AB  - This study investigated for the first time brain ischemic involvement in 19
      consecutive neurologically asymptomatic PNH patients by non-enhanced cerebral
      MRI, and by intracranial arterial and venous angio-MRI. Eleven cases (58%, 7 aged
      <65) showed pathological findings: 9 white matter (WM) abnormalities related to
      chronic ischemic small vessel disease, 2 a focal abnormality >5 mm, and 5 cases a
      score >4 by the age-related white matter changes (ARWMC) scale. Compared with age
      and sex-matched controls (1:2 ratio), patients showed an increased frequency of
      periventricular WM vascular degeneration (32% versus 5.2%, p = 0.04) and of
      severe lesions (ARWMC scale score >4) (26% versus 2.6%, p = 0.05), and a higher
      overall ARWMC scale score (3.5 +/- 1.07 versus 2.0 +/- 0.8, mean +/- SD, p <
      0.0001). Notably, vascular abnormalities suspected for prior partial venous
      thrombosis, were observed in PNH cases only. MRI lesions were not related to
      blood counts, hemolytic markers, clone size, disease duration, and therapy with
      eculizumab. Neurological examination was unremarkable in all patients but one
      (Parkinson disease). Psychiatric assessment revealed a case of generalized
      anxiety disorder, 1 bipolar disorder type 2, and 1 adjustment disorder. In
      conclusion, brain MRI may be useful at diagnosis and during the course of the
      disease to explore subclinical neurological involvement.

PMID- 29323200
TI  - Heat Transfer Enhancement During Water and Hydrocarbon Condensation on Lubricant
      Infused Surfaces.
AB  - Vapor condensation is routinely used as an effective means of transferring heat
      or separating fluids. Dropwise condensation, where discrete droplets form on the
      condenser surface, offers a potential improvement in heat transfer of up to an
      order of magnitude compared to filmwise condensation, where a liquid film covers
      the surface. Low surface tension fluid condensates such as hydrocarbons pose a
      unique challenge since typical hydrophobic condenser coatings used to promote
      dropwise condensation of water often do not repel fluids with lower surface
      tensions. Recent work has shown that lubricant infused surfaces (LIS) can promote
      droplet formation of hydrocarbons. In this work, we confirm the effectiveness of
      LIS in promoting dropwise condensation by providing experimental measurements of
      heat transfer performance during hydrocarbon condensation on a LIS, which
      enhances heat transfer by ~450% compared to an uncoated surface. We also explored
      improvement through removal of noncondensable gases and highlighted a failure
      mechanism whereby shedding droplets depleted the lubricant over time. Enhanced
      condensation heat transfer for low surface tension fluids on LIS presents the
      opportunity for significant energy savings in natural gas processing as well as
      improvements in thermal management, heating and cooling, and power generation.

PMID- 29323201
TI  - Landmark detection in 2D bioimages for geometric morphometrics: a multi
      resolution tree-based approach.
AB  - The detection of anatomical landmarks in bioimages is a necessary but tedious
      step for geometric morphometrics studies in many research domains. We propose
      variants of a multi-resolution tree-based approach to speed-up the detection of
      landmarks in bioimages. We extensively evaluate our method variants on three
      different datasets (cephalometric, zebrafish, and drosophila images). We identify
      the key method parameters (notably the multi-resolution) and report results with
      respect to human ground truths and existing methods. Our method achieves
      recognition performances competitive with current existing approaches while being
      generic and fast. The algorithms are integrated in the open-source Cytomine
      software and we provide parameter configuration guidelines so that they can be
      easily exploited by end-users. Finally, datasets are readily available through a
      Cytomine server to foster future research.

PMID- 29323203
TI  - An epidemiological study of the risk factors associated with myopia in young
      adult men in Korea.
AB  - The prevalence of myopia has been increasing worldwide. Its causes are not
      completely clear, although genetic and environmental factors are thought to play
      a role. Data were collected by the Korean Military Manpower Administration.
      Frequency analysis was used for comparisons of general characteristics. Pearson's
      chi-square tests and logistic regression analysis were used to verify the
      correlations between possible risk factors and the prevalence of myopia or high
      myopia. The prevalence of myopia (50.6-53.0%) and high myopia (11.3-12.9%)
      increased each year. These tended to be the highest in patients born in spring,
      and decreased in the following order according to education level: 4- or 6-year
      university education or more, high school education or less, and 2- to 3-year
      college education. Moreover, the prevalence of myopia and high myopia was
      significantly higher in patients <= 60 kg and with a body mass index <= 18.5
      kg/m2. The prevalence of high myopia was significantly higher in taller patients
      (>=175 cm). The prevalence of myopia and high myopia increased each year in
      Korean young adult men and was associated with birth season, education level,
      height, weight, and body mass index. Tall, lean men were more likely to have high
      myopia.

PMID- 29323205
TI  - Unsupervised Learning and Pattern Recognition of Biological Data Structures with
      Density Functional Theory and Machine Learning.
AB  - By introducing the methods of machine learning into the density functional
      theory, we made a detour for the construction of the most probable density
      function, which can be estimated by learning relevant features from the system of
      interest. Using the properties of universal functional, the vital core of density
      functional theory, the most probable cluster numbers and the corresponding
      cluster boundaries in a studying system can be simultaneously and automatically
      determined and the plausibility is erected on the Hohenberg-Kohn theorems. For
      the method validation and pragmatic applications, interdisciplinary problems from
      physical to biological systems were enumerated. The amalgamation of uncharged
      atomic clusters validated the unsupervised searching process of the cluster
      numbers and the corresponding cluster boundaries were exhibited likewise. High
      accurate clustering results of the Fisher's iris dataset showed the feasibility
      and the flexibility of the proposed scheme. Brain tumor detections from low
      dimensional magnetic resonance imaging datasets and segmentations of high
      dimensional neural network imageries in the Brainbow system were also used to
      inspect the method practicality. The experimental results exhibit the successful
      connection between the physical theory and the machine learning methods and will
      benefit the clinical diagnoses.

PMID- 29323204
TI  - Calcium-phosphate complex increased during subchondral bone remodeling affects
      earlystage osteoarthritis.
AB  - An activation of osteoclasts and subchondral bone remodeling is a major
      histologic feature of early-stage osteoarthritis (OA), which can be accompanied
      by an increase of calcium (Ca) and phosphate (Pi) level in the subchondral
      milieu. Considering articular cartilage gets most of nutrition from subchondral
      bone by diffusion, these micro-environmental changes in subchondral bone can
      affect the physiology of articular chondrocytes. Here, we have shown that Ca is
      increased and co-localized with Pi in articular cartilage of early-stage OA. The
      Ca-Pi complex increased the production of MMP-3 and MMP-13 in the hypertrophic
      chondrocytes, which was dependent on nuclear factor-kappa B (NF-kB), p38 and
      extracellular signal-regulated kinase (Erk) 1/2 mitogen-activated protein (MAP)
      kinase and Signal transducer and activator of transcription 3 (STAT3) signaling.
      The Ca-Pi complexes increased the expression of endocytosis markers, and the
      inhibition of the formation of the Ca-Pi complex ameliorated the Ca-Pi complex
      mediated increases of MMPs expression in hypertrophic chondrocytes. Our data
      provide insight regarding the Ca-Pi complex as a potential catabolic mediator in
      the subchondral milieu and support the pathogenic role of subchondral bone in the
      early stages of cartilage degeneration.

PMID- 29323206
TI  - Effects of Bt cabbage pollen on the honeybee Apis mellifera L.
AB  - Honeybees may be exposed to insecticidal proteins from transgenic plants via
      pollen during their foraging activity. Assessing effects of such exposures on
      honeybees is an essential part of the risk assessment process for transgenic
      Bacillus thuringiensis (Bt) cabbage. Feeding trials were conducted in a
      laboratory setting to test for possible effects of Cry1Ba3 cabbage pollen on
      Italian-derived honeybees Apis mellifera L. Newly emerged A. mellifera were fed
      transgenic pollen, activated Cry1Ba3 toxin, pure sugar syrup (60% w/v sucrose
      solution), and non-transgenic cabbage pollen, respectively. Then the effects on
      survival, pollen consumption, weight, detoxification enzyme activity and midgut
      enzyme activity of A. mellifera were monitored. The results showed that there
      were no significant differences in survival, pollen consumption, weight,
      detoxification enzyme activity among all treatments. No significant differences
      in the activities of total proteolytic enzyme, active alkaline trypsin-like
      enzyme and weak alkaline trypsin-like enzyme were observed among all treatments.
      These results indicate that the side-effects of the Cry1Ba3 cabbage pollen on A.
      mellifera L. are unlikely.

PMID- 29323202
TI  - Genome-based classification of micromonosporae with a focus on their
      biotechnological and ecological potential.
AB  - There is a need to clarify relationships within the actinobacterial genus
      Micromonospora, the type genus of the family Micromonosporaceae, given its
      biotechnological and ecological importance. Here, draft genomes of 40
      Micromonospora type strains and two non-type strains are made available through
      the Genomic Encyclopedia of Bacteria and Archaea project and used to generate a
      phylogenomic tree which showed they could be assigned to well supported phyletic
      lines that were not evident in corresponding trees based on single and
      concatenated sequences of conserved genes. DNA G+C ratios derived from genome
      sequences showed that corresponding data from species descriptions were
      imprecise. Emended descriptions include precise base composition data and
      approximate genome sizes of the type strains. antiSMASH analyses of the draft
      genomes show that micromonosporae have a previously unrealised potential to
      synthesize novel specialized metabolites. Close to one thousand biosynthetic gene
      clusters were detected, including NRPS, PKS, terpenes and siderophores clusters
      that were discontinuously distributed thereby opening up the prospect of
      prioritising gifted strains for natural product discovery. The distribution of
      key stress related genes provide an insight into how micromonosporae adapt to key
      environmental variables. Genes associated with plant interactions highlight the
      potential use of micromonosporae in agriculture and biotechnology.

PMID- 29323207
TI  - Discovery of Hepatotoxic Equivalent Combinatorial Markers from Dioscorea
      bulbifera tuber by Fingerprint-Toxicity Relationship Modeling.
AB  - Due to extremely chemical complexity, identification of potential toxicity
      related constituents from an herbal medicine (HM) still remains challenging.
      Traditional toxicity-guided separation procedure suffers from time- and labor
      consumption and neglects the additive effect of multi-components. In this study,
      we proposed a screening strategy called "hepatotoxic equivalent combinatorial
      markers (HECMs)" for a hepatotoxic HM, Dioscorea bulbifera tuber (DBT). Firstly,
      the chemical constituents in DBT extract were globally characterized. Secondly,
      the fingerprints of DBT extracts were established and their in vivo
      hepatotoxicities were tested. Thirdly, three chemometric tools including partial
      least squares regression (PLSR), back propagation-artificial neural network (BP
      ANN) and cluster analysis were applied to model the fingerprint-hepatotoxicity
      relationship and to screen hepatotoxicity-related markers. Finally, the chemical
      combination of markers was subjected to hepatotoxic equivalence evaluation. A
      total of 40 compounds were detected or tentatively characterized. Two diterpenoid
      lactones, 8-epidiosbulbin E acetate (EEA) and diosbulbin B (DIOB), were
      discovered as the most hepatotoxicity-related markers. The chemical combination
      of EEA and DIOB, reflecting the whole hepatotoxicity of original DBT extract with
      considerable confidential interval, was verified as HECMs for DBT. The present
      study is expected not only to efficiently discover hepatotoxicity-related markers
      of HMs, but also to rationally evaluate/predict the hepatotoxicity of HMs.

PMID- 29323209
TI  - Hydrological simulation and uncertainty analysis using the improved TOPMODEL in
      the arid Manas River basin, China.
AB  - Understanding the mechanism of complicated hydrological processes is important
      for sustainable management of water resources in an arid area. This paper carried
      out the simulations of water movement for the Manas River Basin (MRB) using the
      improved semi-distributed Topographic hydrologic model (TOPMODEL) with a snowmelt
      model and topographic index algorithm. A new algorithm is proposed to calculate
      the curve of topographic index using internal tangent circle on a conical
      surface. Based on the traditional model, the improved indicator of temperature
      considered solar radiation is used to calculate the amount of snowmelt. The
      uncertainty of parameters for the TOPMODEL model was analyzed using the
      generalized likelihood uncertainty estimation (GLUE) method. The proposed model
      shows that the distribution of the topographic index is concentrated in high
      mountains, and the accuracy of runoff simulation has certain enhancement by
      considering radiation. Our results revealed that the performance of the improved
      TOPMODEL is acceptable and comparable to runoff simulation in the MRB. The
      uncertainty of the simulations resulted from the parameters and structures of
      model, climatic and anthropogenic factors. This study is expected to serve as a
      valuable complement for widely application of TOPMODEL and identify the mechanism
      of hydrological processes in arid area.

PMID- 29323208
TI  - Composition of salivary microbiota in elderly subjects.
AB  - Frailty is gaining attention worldwide with the aging of society. Despite the
      potential lethality and multiple signs and symptoms in affected individuals,
      preclinical detection of early manifestations leading to frailty syndrome have
      not been established. We speculated that the composition of the oral microbiota
      is associated with general frailty, as well as a relationship between gut
      microbiota and general health condition. In the present study, we investigated
      the salivary microbiota composition in samples from healthy and frail elderly
      individuals using 16S rRNA sequencing analysis for characterization. We found a
      significant difference in diversity between elderly individuals living in a
      nursing home (EN) and healthy control (HC) subjects, as well as in the microbiota
      composition at the phyla level. A supervised orthogonal partial least squared
      discriminant analysis (OPLS-DA) revealed a significant difference in clear
      classification trend between the EN and HC groups, with all observations falling
      within the Hotellings T2 (0.95) ellipse, with model fitness parameters of R
      2(cum) = 0.937 and Q 2(cum) = 0.888, respectively. In addition, the score plots
      by unsupervised principal component analysis (PCA) showed a clear classification
      trend in both groups. Our findings suggest that general frailty is associated
      with oral microbiota composition and formation.

PMID- 29323211
TI  - Single-pixel imaging with Morlet wavelet correlated random patterns.
AB  - Single-pixel imaging is an indirect imaging technique which utilizes simplified
      optical hardware and advanced computational methods. It offers novel solutions
      for hyper-spectral imaging, polarimetric imaging, three-dimensional imaging,
      holographic imaging, optical encryption and imaging through scattering media. The
      main limitations for its use come from relatively high measurement and
      reconstruction times. In this paper we propose to reduce the required signal
      acquisition time by using a novel sampling scheme based on a random selection of
      Morlet wavelets convolved with white noise. While such functions exhibit random
      properties, they are locally determined by Morlet wavelet parameters. The
      proposed method is equivalent to random sampling of the properly selected part of
      the feature space, which maps the measured images accurately both in the spatial
      and spatial frequency domains. We compare both numerically and experimentally the
      image quality obtained with our sampling protocol against widely-used sampling
      with Walsh-Hadamard or noiselet functions. The results show considerable
      improvement over the former methods, enabling single-pixel imaging at low
      compression rates on the order of a few percent.

PMID- 29323210
TI  - Anticancer potentiality of lignan rich fraction of six Flaxseed cultivars.
AB  - The objective of our study is to highlight the therapeutic effect and mechanism
      of action by which purified Flaxseed hydrolysate (PFH) which is a lignan rich
      fraction exerts its anticancer activity on a human breast cancer cell line (T47D)
      and in mice bearing tumor. HPLC analysis of PFH of six flaxseed cultivars had
      shown that PFH of the cultivar Giza 9 (PFH-G9) contains the highest concentration
      of SDG (81.64 mg/g). The in vitro cytotoxic potentiality of PFH's of six flaxseed
      cultivars was screened against a panel of human cancer cell lines. PFH -G9 showed
      the most significant cytotoxic activity against ER-receptor positive breast cell
      lines MCF7 and T47D with IC50 13.8 and 15.8 ug/ml, respectively. Moreover, PFH-G9
      reduced the expression of the metastasis marker, 1-alpha, metalloproteinases and
      vascular endothelial growth factor (VEGF), one of the most potent stimulators of
      angiogenesis, while it increased the caspase-3 dependent apoptosis. Our study
      also showed that dietary intake of 10% of Giza 9 Flaxseeds (FS), fixed oil (FSO)
      or Flax meal (FSM) twice daily for 3 weeks in mice-bearing solid Ehrlich ascites
      carcinoma (EAC) resulted in reducing the tumor volume, the expression of
      estrogen, insulin growth factor, progesterone, VEGF and MMP-2, but enhanced
      expression of caspase-3.

PMID- 29323213
TI  - High-temperature quantum oscillations of the Hall resistance in bulk Bi2Se3.
AB  - Helically spin-polarized Dirac fermions (HSDF) in protected topological surface
      states (TSS) are of high interest as a new state of quantum matter. In three
      dimensional (3D) materials with TSS, electronic bulk states often mask the
      transport properties of HSDF. Recently, the high-field Hall resistance and low
      field magnetoresistance indicate that the TSS may coexist with a layered two
      dimensional electronic system (2DES). Here, we demonstrate quantum oscillations
      of the Hall resistance at temperatures up to 50 K in nominally undoped bulk
      Bi2Se3 with a high electron density n of about 2.1019 cm-3. From the angular and
      temperature dependence of the Hall resistance and the Shubnikov-de Haas
      oscillations we identify 3D and 2D contributions to transport. Angular resolved
      photoemission spectroscopy proves the existence of TSS. We present a model for
      Bi2Se3 and suggest that the coexistence of TSS and 2D layered transport
      stabilizes the quantum oscillations of the Hall resistance.

PMID- 29323212
TI  - Multimodal tumor-homing chitosan oligosaccharide-coated biocompatible palladium
      nanoparticles for photo-based imaging and therapy.
AB  - Palladium, a near-infrared plasmonic material has been recognized for its use in
      photothermal therapy as an alternative to gold nanomaterials. However, its
      potential application has not been explored well in biomedical applications. In
      the present study, palladium nanoparticles were synthesized and the surface of
      the particles was successfully modified with chitosan oligosaccharide (COS),
      which improved the biocompatibility of the particles. More importantly, the
      particles were functionalized with RGD peptide, which improves particle
      accumulation in MDA-MB-231 breast cancer cells and results in enhanced
      photothermal therapeutic effects under an 808-nm laser. The RGD peptide-linked,
      COS-coated palladium nanoparticles (Pd@COS-RGD) have good biocompatibility, water
      dispersity, and colloidal and physiological stability. They destroy the tumor
      effectively under 808-nm laser illumination at 2 W cm-2 power density. Further,
      Pd@COS-RGD gives good amplitude of photoacoustic signals, which facilitates the
      imaging of tumor tissues using a non-invasive photoacoustic tomography system.
      Finally, the fabricated Pd@COS-RGD acts as an ideal nanotheranostic agent for
      enhanced imaging and therapy of tumors using a non-invasive near-infrared laser.

PMID- 29323214
TI  - Real-time Humidity Sensor Based on Microwave Resonator Coupled with PEDOT:PSS
      Conducting Polymer Film.
AB  - A real-time humidity sensor based on a microwave resonator coupled with a
      poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) conducting
      polymer (CP) film is proposed in this paper. The resonator is patterned on a
      printed circuit board and is excited by electromagnetic field coupling. To
      enhance the sensitivity of the sensor, the CP film is located in the area with
      the strongest electric field in the resonator. To investigate the performance,
      the proposed sensor is placed alongside a reference sensor in a humidity chamber,
      and humidity is injected at room temperature. The experimental results indicate
      that the electrical properties of the resonator with the CP film, such as the
      transmission coefficient (S 21) and resonance frequency, change with the relative
      humidity (RH). Specifically, as the RH changes from 5% to 80%, S 21 and the
      resonance frequency change simultaneously. Moreover, the proposed sensor exhibits
      great repeatability in the middle of the sensing range, which is from 40% to 60%
      RH. Consequently, our resonator coupled with the CP film can be used as a real
      time humidity-sensing device in the microwave range, where various radio
      frequency devices are in use.

PMID- 29323215
TI  - Green tea extract attenuates LPS-induced retinal inflammation in rats.
AB  - Inflammation is in a wide spectrum of retinal diseases, causing irreversible
      blindness and visual impairment. We have previously demonstrated that Green Tea
      Extract (GTE) is a potent anti-inflammatory agent for anterior uveitis. Here we
      investigated the anti-inflammatory effect of GTE on lipopolysaccharides (LPS)
      induced retinal inflammation in rats and explored the underlying mechanism. Adult
      rats were injected with LPS and GTE was administered intra-gastrically at 2, 8,
      26 and 32 hours post-injection. Staining of whole-mount retina showed that the
      number of activated microglia cells was significantly increased at 48 hours post
      injection, which was suppressed after GTE treatment in a dose-dependent manner.
      Activation of astrocytes and Muller glia in the retina was also suppressed after
      GTE treatment. Meanwhile, GTE reduced the expression of pro-inflammatory
      cytokines including IL-1beta, TNF-alpha and IL-6 in retina and vitreous humor.
      These anti-inflammatory effects were associated with a reduced phosphorylation of
      STAT3 and NF-kappaB in the retina. Furthermore, the surface receptor of EGCG,
      67LR, was localized on the neurons and glia in the retina. These findings
      demonstrate that GTE is an effective agent in suppressing LPS-induced retinal
      inflammation, probably through its potent anti-oxidative property and a receptor
      mediated action on transcription factors that regulate production of pro
      inflammatory cytokines.

PMID- 29323216
TI  - Characterization of isoprene-derived secondary organic aerosols at a rural site
      in North China Plain with implications for anthropogenic pollution effects.
AB  - Isoprene is the most abundant non-methane volatile organic compound (VOC) and the
      largest contributor to secondary organic aerosol (SOA) burden on a global scale.
      In order to examine the influence of high concentrations of anthropogenic
      pollutants on isoprene-derived SOA (SOA i ) formation, summertime PM2.5 filter
      samples were collected with a three-hour sampling interval at a rural site in the
      North China Plain (NCP), and determined for SOA i tracers and other chemical
      species. RO2+NO pathway derived 2-methylglyceric acid presented a relatively
      higher contribution to the SOA i due to the high-NOx (~20 ppb) conditions in the
      NCP that suppressed the reactive uptake of RO2+HO2 reaction derived isoprene
      epoxydiols. Compared to particle acidity and water content, sulfate plays a
      dominant role in the heterogeneous formation process of SOA i . Diurnal variation
      and correlation of 2-methyltetrols with ozone suggested an important effect of
      isoprene ozonolysis on SOA i formation. SOA i increased linearly with
      levoglucosan during June 10-18, which can be attributed to an increasing emission
      of isoprene caused by the field burning of wheat straw and a favorable aqueous
      SOA formation during the aging process of the biomass burning plume. Our results
      suggested that isoprene oxidation is highly influenced by intensive anthropogenic
      activities in the NCP.

PMID- 29323217
TI  - Node of Ranvier as an Array of Bio-Nanoantennas for Infrared Communication in
      Nerve Tissue.
AB  - Electromagnetic radiation, in the visible and infrared spectrum, is increasingly
      being investigated for its possible role in the most evolved brain capabilities.
      Beside experimental evidence of electromagnetic cellular interactions, the
      possibility of light propagation in the axon has been recently demonstrated using
      computational modelling, although an explanation of its source is still not
      completely understood. We studied electromagnetic radiation onset and propagation
      at optical frequencies in myelinated axons, under the assumption that ion channel
      currents in the node of Ranvier behave like an array of nanoantennas emitting in
      the wavelength range from 300 to 2500 nm. Our results suggest that the
      wavelengths below 1600 nm are most likely to propagate throughout myelinated
      segments. Therefore, a broad wavelength window exists where both generation and
      propagation could happen, which in turn raises the possibility that such a
      radiation may play some role in neurotransmission.

PMID- 29323218
TI  - Scanning electron microscopy assessment of the Descemet membrane interface during
      DMEK graft preparation.
AB  - We set out to determine microscopic characteristics of the Descemet membrane
      interface during Descemet membrane endothelial keratoplasty (DMEK) graft
      preparation. Ten corneas were partially prepared, preserving half of the Descemet
      membrane attached to the stroma to enable visualisation of the Descemet-stroma
      interface. This tissue was prepared for viewing with a scanning electron
      microscope. The Descemet-stroma interface was categorised into three regions:
      centre, mid-periphery and periphery. We classified adhesions in these regions as
      either minor thread-like adhesions or major bridge-like adhesions with stromal
      detachments. We found a region-specific differentiation of the Descemet-stroma
      morphology. The presence of minor (P = 0,0001) and major (P = 0,0001) adhesions
      at the explored regions of the Descemet-stroma interface were found to be
      statistically significant. Fibrotic linear adhesions were predominant in the
      centre and mid-periphery, whereas the larger bridge-like adhesions were found
      mainly in the periphery. In addition, we observed a positive correlation between
      the size of the adhesions and the presence of ruptures in the underlying stromal
      bed. Viewing of the Descemet-stroma interface with electron microscopy reveals
      morphological differences between the centre of a graft and its periphery. These
      findings are of potential clinical relevance in terms of developing a better
      understanding of tissue behaviour during graft preparation.

PMID- 29323219
TI  - Electromagnetic Radiation Disturbed the Photosynthesis of Microcystis aeruginosa
      at the Proteomics Level.
AB  - Photosynthesis of Microcystis aeruginosa under Electromagnetic Radiation (1.8
      GHz, 40 V/m) was studied by using the proteomics. A total of 30 differentially
      expressed proteins, including 15 up-regulated and 15 down-regulated proteins,
      were obtained in this study. The differentially expressed proteins were
      significantly enriched in the photosynthesis pathway, in which the protein
      expression levels of photosystems II cytochrome b559 alpha subunit, cytochrome
      C550, PsbY, and F-type ATP synthase (a, b) decreased. Our results indicated that
      electromagnetic radiation altered the photosynthesis-related protein expression
      levels, and aimed at the function of photosynthetic pigments, photosystems II
      potential activity, photosynthetic electron transport process, and photosynthetic
      phosphorylation process of M. aeruginosa. Based on the above evidence, that
      photoreaction system may be deduced as a target of electromagnetic radiation on
      the photosynthesis in cyanobacteria; the photoreaction system of cyanobacteria is
      a hypothetical "shared target effector" that responds to light and
      electromagnetic radiation; moreover, electromagnetic radiation does not act on
      the functional proteins themselves but their expression processes.

PMID- 29323220
TI  - An efficient, flexible perovskite solar module exceeding 8% prepared with an
      ultrafast PbI2 deposition rate.
AB  - Large-area, pinhole-free CH3NH3PbI3 perovskite thin films were successfully
      fabricated on 5 cm * 5 cm flexible indium tin oxide coated polyethylene
      naphthalate (ITO-PEN) substrates through a sequential evaporation/spin-coating
      deposition method in this research. The influence of the rate-controlled
      evaporation of PbI2 films on the quality of the perovskite layer and the final
      performance of the planar-structured perovskite solar cells were investigated. An
      ultrafast evaporation rate of 20 A s-1 was found to be most beneficial for the
      conversion of PbI2 to CH3NH3PbI3 perovskite. Based on this high-quality
      CH3NH3PbI3 film, a resultant flexible perovskite solar sub-module (active area of
      16 cm2) with a power conversion efficiency of more than 8% and a 1.2 cm2 flexible
      perovskite solar cell with a power conversion efficiency of 12.7% were obtained.

PMID- 29323221
TI  - Chemotherapy plus Panitumumab Versus Chemotherapy plus Bevacizumab in Metastatic
      Colorectal Cancer: A Meta-analysis.
AB  - Panitumumab and bevacizumab have been widely used in combination with
      chemotherapy for patients with wild type RAS metastatic colorectal cancer (mCRC).
      Whether panitumumab or bevacizumab was the optimal option remained controversial.
      Thus, we conducted a meta-anaylsis to evaluate chemotherapy plus panitumumab (C +
      P) versus chemotherapy plus bevacizumab (C + B) in wild type RAS mCRC. Electronic
      databases including PubMed, Embase, and Web of Science, Cochrane Library,
      ClinicalTrials.gov, were searched. This meta-analysis estimated the progression
      free survival (PFS), overall survival (OS), overall response rate (ORR) and
      adverse events (AEs). Three randomized controlled trials with a total number of
      577 patients were included. In wild type RAS population, PFS [hazard ratio (HR) =
      0.96; 95% confidence interval (CI), 0.76 to 1.15] and OS (HR = 0.90; 95% CI, 0.54
      to 1.27) and ORR [relative ratio (RR) = 2.06; 95% CI, 0.86 to 4.90] appeared
      similar between the two treatments, the incidence of AEs slightly increased (RR =
      1.16; 95% CI 1.08 to 1.26). In conclusion, there was insufficient evidence to
      precisely conclude that combination treatment of C + P had an improved efficacy
      compared with C + B. Further large-scale and better-designed clinical trials are
      still needed to evaluate the combination treatment of C + P in patients with wild
      type RAS mCRC.

PMID- 29323223
TI  - On the efficiency of nature-inspired metaheuristics in expensive global
      optimization with limited budget.
AB  - Global optimization problems where evaluation of the objective function is an
      expensive operation arise frequently in engineering, decision making, optimal
      control, etc. There exist two huge but almost completely disjoint communities
      (they have different journals, different conferences, different test functions,
      etc.) solving these problems: a broad community of practitioners using stochastic
      nature-inspired metaheuristics and people from academia studying deterministic
      mathematical programming methods. In order to bridge the gap between these
      communities we propose a visual technique for a systematic comparison of global
      optimization algorithms having different nature. Results of more than 800,000
      runs on 800 randomly generated tests show that both stochastic nature-inspired
      metaheuristics and deterministic global optimization methods are competitive and
      surpass one another in dependence on the available budget of function
      evaluations.

PMID- 29323222
TI  - A triangle study of human, instrument and bioelectronic nose for non-destructive
      sensing of seafood freshness.
AB  - Because the freshness of seafood determines its consumer preference and food
      safety, the rapid monitoring of seafood deterioration is considered essential.
      However, the conventional analysis of seafood deterioration using chromatography
      instruments and bacterial colony counting depends on time-consuming and food
      destructive treatments. In this study, we demonstrate a non-destructive and rapid
      food freshness monitoring system by a triangular study of sensory evaluation, gas
      chromatography-mass spectroscopy (GC-MS), and a bioelectronic nose. The sensory
      evaluation indicated that the acceptability and flavor deteriorated gradually
      during post-harvest storage (4  degrees C) for 6 days. The GC-MS analysis
      recognized the reduction of freshness by detecting a generation of dimethyl
      sulfide (DMS) from the headspace of oyster in a refrigerator (4  degrees C) at 4
      days post-harvest. However, the bioelectronic nose incorporating human olfactory
      receptor peptides with the carbon nanotube field-effect transistor sensed
      trimethylamine (TMA) from the oyster at 2 days post-harvest with suggesting early
      recognition of oysters' quality and freshness deterioration. Given that the
      bacterial species producing DMS or TMA along with toxins were found in the
      oyster, the bacterial contamination-driven food deterioration is rapidly
      monitored using the bioelectronic nose with a targeted non-destructive freshness
      marker.

PMID- 29323224
TI  - X-ray diffraction tomography with limited projection information.
AB  - X-ray diffraction tomography (XDT) records the spatially-resolved X-ray
      diffraction profile of an extended object. Compared to conventional transmission
      based tomography, XDT displays high intrinsic contrast among materials of similar
      electron density and improves the accuracy in material identification thanks to
      the molecular structural information carried by diffracted photons. However, due
      to the weak diffraction signal, a tomographic scan covering the entire object
      typically requires a synchrotron facility to make the acquisition time more
      manageable. Imaging applications in medical and industrial settings usually do
      not require the examination of the entire object. Therefore, a diffraction
      tomography modality covering only the region of interest (ROI) and subsequent
      image reconstruction techniques with truncated projections are highly desirable.
      Here we propose a table-top diffraction tomography system that can resolve the
      spatially-variant diffraction form factor from internal regions within extended
      samples. We demonstrate that the interior reconstruction maintains the material
      contrast while reducing the imaging time by 6 folds. The presented method could
      accelerate the acquisition of XDT and be applied in portable imaging applications
      with a reduced radiation dose.

PMID- 29323225
TI  - Frequent implementation of interventions may increase HIV infections among MSM in
      China.
AB  - Intervention measures among men who have sex with men (MSM) are usually designed
      to reduce the frequency of high risk behaviors (within-community level), but
      unfortunately may change the contact network and consequently increase the
      opportunity for them to have sex with new partners (between-community level). A
      multi-community periodic model on complex network is proposed to study the two
      side effects of interventions on HIV transmission among MSM in China, in which
      the wanning process of the impacts of interventions are modelled. The basic
      reproduction number for the multi-community periodic system is defined and
      calculated numerically. Based on the number of annual reported HIV/AIDS cases
      among MSM in China, the unknown parameters are estimated by using MCMC method and
      the basic reproduction number is estimated as 3.56 (95%CI [3.556, 3.568]). Our
      results show that strong randomness of the community-connection networks leads to
      more new infections and more HIV/AIDS cases. Moreover, main conclusion indicates
      that implementation of interventions may induce more new infections, depending on
      relative level of between- and within-community impacts, and the frequency of
      implementation of interventions. The findings can help to guide the policy maker
      to choose the appropriate intervention measures, and to implement the
      interventions with proper frequency.

PMID- 29323226
TI  - Lateral and Basal Amygdala Account for Opposite Behavioral Responses during the
      Long-Term Expression of Fearful Memories.
AB  - Memories of fearful events can be maintained throughout the lifetime of animals.
      Here we showed that lesions of the lateral nucleus (LA) performed shortly after
      training impaired the retention of long-term memories, assessed by the
      concomitant measurement of two dissociable defensive responses, freezing and
      avoidance in rats. Strikingly, when LA lesions were performed four weeks after
      training, rats did not show freezing to a learned threat stimulus, but they were
      able to direct their responses away from it. Similar results were found when the
      central nucleus (CeA) was lesioned four weeks after training, whereas lesions of
      the basal nucleus (BA) suppressed avoidance without affecting freezing. LA and BA
      receive parallel inputs from the auditory cortex, and optogenetic inhibition of
      these terminals hampered both freezing and avoidance. We therefore propose that,
      at variance with the traditional serial flow of information model, long-term
      fearful memories recruit two parallel circuits in the amygdala, one relying on
      the LA-to-CeA pathway and the other relying solely on BA, which operate
      independently and mediate distinct defensive responses.

PMID- 29323227
TI  - Rapid Biochemical Mixture Screening by Three-Dimensional Patterned
      Multifunctional Substrate with Ultra-Thin Layer Chromatography (UTLC) and Surface
      Enhanced Raman Scattering (SERS).
AB  - We present a three-dimensional patterned (3DP) multifunctional substrate with the
      functions of ultra-thin layer chromatography (UTLC) and surface enhanced Raman
      scattering (SERS), which simultaneously enables mixture separation, target
      localization and label-free detection. This multifunctional substrate is
      comprised of a 3DP silicon nanowires array (3DP-SiNWA), decorated with silver
      nano-dendrites (AgNDs) atop. The 3DP-SiNWA is fabricated by a facile
      photolithographic process and low-cost metal assisted chemical etching (MaCE)
      process. Then, the AgNDs are decorated onto 3DP-SiNWA by a wet chemical reduction
      process, obtaining 3DP-AgNDs@SiNWA multifunctional substrates. With various
      patterns designed on the substrates, the signal intensity could be maximized by
      the excellent confinement and concentrated effects of patterns. By using this 3DP
      AgNDs@SiNWA substrate to scrutinize the mixture of two visible dyes, the
      individual target could be recognized and further boosted the Raman signal of
      target 15.42 times comparing to the un-patterned AgNDs@SiNWA substrate.
      Therefore, such a three-dimensional patterned multifunctional substrate empowers
      rapid mixture screening, and can be readily employed in practical applications
      for biochemical assays, food safety and other fields.

PMID- 29323228
TI  - Relationships between type of pain and work participation in people with long
      standing spinal cord injury: results from a cross-sectional study.
AB  - STUDY DESIGN: Multicentre, cross-sectional study. OBJECTIVES: To describe the
      relationships between the presence of (different types of) pain and participation
      in paid work in people with long-standing spinal cord injury (SCI). Furthermore,
      the associations of pain-related work limitations, age, gender, relationship,
      education, lesion level, and time since injury (TSI) with work participation (WP)
      were investigated. SETTING: The Netherlands. METHODS: Individuals (n = 265) with
      SCI for >= 10 years were included. Data were collected through a structured
      consultation with a rehabilitation physician and self-report questionnaire.
      Descriptive statistics and logistic regression analysis were performed. RESULTS:
      Median age of participants was 47.9 years, median time since injury was 22 years,
      73% were male, 69% had complete SCI and 59% had paraplegia, 50% had paid work,
      63% reported musculoskeletal pain, 49% reported neuropathic pain, and 31%
      reported other pain. Self-reported pain-related work limitations were
      significantly (V = 0.26 and V = 0.27) related to WP. In bivariable logistic
      regression analyses, no statistically significant relationships between type of
      pain and WP were observed. Younger age (OR=0.96), male gender (OR=0.52), a stable
      relationship (OR = 1.70), and shorter time since SCI (OR = 0.97) were
      significantly associated with a higher chance of being employed. Multivariable
      analysis confirmed these findings and in addition showed a higher level of
      education to be positively related with WP. CONCLUSION: Age, gender,
      relationship, education, TSI and self-reported work limitations showed a
      relationship with WP. Different types of pain were unrelated to WP. SPONSORSHIP:
      Fonds NutsOHRA through the Dutch Organization for Health Research and Development
      (ZonMw), Project number 89000006.

PMID- 29323229
TI  - Facile synthesis of TiO2/ZrO2 nanofibers/nitrogen co-doped activated carbon to
      enhance the desalination and bacterial inactivation via capacitive deionization.
AB  - Capacitive deionization, as a second generation electrosorption technique to
      obtain water, is one of the most promising water desalination technologies. Yet;
      in order to achieve high CDI performance, a well-designed structure of the
      electrode materials is needed, and is in high demand. Here, a novel composite
      nitrogen-TiO2/ZrO2 nanofibers incorporated activated carbon (NACTZ) is
      synthesized for the first time with enhanced desalination efficiency as well as
      disinfection performance towards brackish water. Nitrogen and TiO2/ZrO2
      nanofibers are used as the support of activated carbon to improve its low
      capacitance and hydrophobicity, which had dramatically limited its adequacy
      during the CDI process. Importantly, the as-fabricated NACTZ nanocomposite
      demonstrates enhanced electrochemical performance with significant specific
      capacitance of 691.78 F g-1, low internal resistance and good cycling stability.
      In addition, it offers a high capacitive deionization performance of NACTZ yield
      with electrosorptive capacity of 3.98 mg g-1, and, good antibacterial effects as
      well. This work will provide an effective solution for developing highly
      performance and low-cost design for CDI electrode materials.

PMID- 29323230
TI  - Developing an in silico minimum inhibitory concentration panel test for
      Klebsiella pneumoniae.
AB  - Antimicrobial resistant infections are a serious public health threat worldwide.
      Whole genome sequencing approaches to rapidly identify pathogens and predict
      antibiotic resistance phenotypes are becoming more feasible and may offer a way
      to reduce clinical test turnaround times compared to conventional culture-based
      methods, and in turn, improve patient outcomes. In this study, we use whole
      genome sequence data from 1668 clinical isolates of Klebsiella pneumoniae to
      develop a XGBoost-based machine learning model that accurately predicts minimum
      inhibitory concentrations (MICs) for 20 antibiotics. The overall accuracy of the
      model, within +/-1 two-fold dilution factor, is 92%. Individual accuracies are
      >=90% for 15/20 antibiotics. We show that the MICs predicted by the model
      correlate with known antimicrobial resistance genes. Importantly, the genome-wide
      approach described in this study offers a way to predict MICs for isolates
      without knowledge of the underlying gene content. This study shows that machine
      learning can be used to build a complete in silico MIC prediction panel for K.
      pneumoniae and provides a framework for building MIC prediction models for other
      pathogenic bacteria.

PMID- 29323231
TI  - Mice deficient in the Shmt2 gene have mitochondrial respiration defects and are
      embryonic lethal.
AB  - Accumulation of somatic mutations in mitochondrial DNA (mtDNA) has been proposed
      to be responsible for human aging and age-associated mitochondrial respiration
      defects. However, our previous findings suggested an alternative hypothesis of
      human aging-that epigenetic changes but not mutations regulate age-associated
      mitochondrial respiration defects, and that epigenetic downregulation of nuclear
      coded genes responsible for mitochondrial translation [e.g., glycine C
      acetyltransferase (GCAT), serine hydroxymethyltransferase 2 (SHMT2)] is related
      to age-associated respiration defects. To examine our hypothesis, here we
      generated mice deficient in Gcat or Shmt2 and investigated whether they have
      respiration defects and premature aging phenotypes. Gcat-deficient mice showed no
      macroscopic abnormalities including premature aging phenotypes for up to 9 months
      after birth. In contrast, Shmt2-deficient mice showed embryonic lethality after
      13.5 days post coitum (dpc), and fibroblasts obtained from 12.5-dpc Shmt2
      deficient embryos had respiration defects and retardation of cell growth. Because
      Shmt2 substantially controls production of N-formylmethionine-tRNA (fMet-tRNA) in
      mitochondria, its suppression would reduce mitochondrial translation, resulting
      in expression of the respiration defects in fibroblasts from Shmt2-deficient
      embryos. These findings support our hypothesis that age-associated respiration
      defects in fibroblasts of elderly humans are caused not by mtDNA mutations but by
      epigenetic regulation of nuclear genes including SHMT2.

PMID- 29323232
TI  - Comparison of Bladder Carcinogens in the Urine of E-cigarette Users Versus Non E
      cigarette Using Controls.
AB  - Electronic cigarette (EC) use is gaining popularity as a substitute for
      conventional smoking due to the perception and evidence it represents a safer
      alternative. In contrast to the common perception amongst users that ECs
      represent no risk initial studies have revealed a complex composition of e
      cigarette liquids. Conventional cigarette smoking is a known risk factor for
      developing bladder cancer and prior reports raise concern some of those causative
      compounds may exist in EC liquids or vapor. Urine samples were collected from 13
      e-cigarette using subjects and 10 non e-cigarette using controls. Five known
      bladder carcinogens that are either present in conventional cigarettes, products
      of combustion, or solvents believed to be used in some e-cigarette formulations
      were quantified by liquid chromatography - mass spectrometry (LC-MS). Analysis of
      e-cigarette user urine revealed the presence of two carcinogenic compounds, o
      toluidine and 2-naphthylamine, at a mean 2.3 and 1.3 fold higher concentration (p
      value of 0.0013 and 0.014 respectively). Many of these subjects (9/13) were long
      term nonsmokers (>12 months). Further study is needed to clarify the safety
      profile of e-cigarettes and their contribution to the development of bladder
      cancer given the greater concentration of carcinogenic aromatic amines in the
      urine of e-cigarette users.

PMID- 29323233
TI  - Graphene analogue in (111)-oriented BaBiO3 bilayer heterostructures for
      topological electronics.
AB  - Topological electronics is a new field that uses topological charges as current
      carrying degrees of freedom. For topological electronics applications, systems
      should host topologically distinct phases to control the topological domain
      boundary through which the topological charges can flow. Due to their multiple
      Dirac cones and the pi-Berry phase of each Dirac cone, graphene-like electronic
      structures constitute an ideal platform for topological electronics; graphene can
      provide various topological phases when incorporated with large spin-orbit
      coupling and mass-gap tunability via symmetry-breaking. Here, we propose that a
      (111)-oriented BaBiO3 bilayer (BBL) sandwiched between large-gap perovskite
      oxides is a promising candidate for topological electronics by realizing a gap
      tunable, and consequently a topology-tunable, graphene analogue. Depending on how
      neighboring perovskite spacers are chosen, the inversion symmetry of the BBL
      heterostructure can be either conserved or broken, leading to the quantum spin
      Hall (QSH) and quantum valley Hall (QVH) phases, respectively. BBL sandwiched by
      ferroelectric compounds enables switching of the QSH and QVH phases and generates
      the topological domain boundary. Given the abundant order parameters of the
      sandwiching oxides, the BBL can serve as versatile topological building blocks in
      oxide heterostructures.

PMID- 29323234
TI  - Caveolin 1 Promotes Renal Water and Salt Reabsorption.
AB  - Caveolin-1 (Cav1) is essential for the formation of caveolae. Little is known
      about their functional role in the kidney. We tested the hypothesis that caveolae
      modulate renal salt and water reabsorption. Wild-type (WT) and Cav1-deficient
      (Cav1-/-) mice were studied. Cav1 expression and caveolae formation were present
      in vascular cells, late distal convoluted tubule and principal connecting tubule
      and collecting duct cells of WT but not Cav1-/- kidneys. Urinary sodium excretion
      was increased by 94% and urine flow by 126% in Cav1-/- mice (p < 0.05). A
      decrease in activating phosphorylation of the Na-Cl cotransporter (NCC) of the
      distal convoluted tubule was recorded in Cav1-/- compared to WT kidneys (-40%; p
      < 0.05). Isolated intrarenal arteries from Cav1-/- mice revealed a fourfold
      reduction in sensitivity to phenylephrine (p < 0.05). A significantly diminished
      maximal contractile response (-13%; p < 0.05) was suggestive of enhanced nitric
      oxide (NO) availability. In line with this, the abundance of endothelial NO
      synthase (eNOS) was increased in Cav1-/- kidneys +213%; p < 0.05) and cultured
      caveolae-deprived cells showed intracellular accumulation of eNOS, compared to
      caveolae-intact controls. Our results suggest that renal caveolae help to
      conserve water and electrolytes via modulation of NCC function and regulation of
      vascular eNOS.

PMID- 29323235
TI  - The value of narrow band imaging in diagnosis of head and neck cancer: a meta
      analysis.
AB  - Head and neck cancer is difficult to diagnose early. We aimed to estimate the
      diagnosis value of narrow band imaging(NBI) in head and neck cancers. We
      identified relevant studies through a search of PubMed, Embase and the Cochrane
      Library. We used a random effect model. Subgroup analysis and meta-regression
      analysis were performed to estimate the factors which may influence the
      sensitivity and specificity of the NBI. We included 25 studies with total 6187
      lesions. The pooled sensitivity, specificity, positive likelihood rate, negative
      likelihood rate and diagnostic odds ratios of NBI were 88.5%, 95.6%, 12.33, 0.11
      and 121.26, respectively. The overall area under the curve of SROC was 96.94%.
      The location, type of assessment, type of endoscope system and high definition
      were not significant sources of heterogeneity (P > 0.05). However, magnification
      may be related to the source of heterogeneity (P = 0.0065). Therefore, NBI may be
      a promising endoscopic tool in the diagnosis of head and neck cancer.

PMID- 29323237
TI  - Racial Differences in Four Leukemia Subtypes: Comprehensive Descriptive
      Epidemiology.
AB  - : Leukemia is a malignant progressive disease and has four major subtypes.
      Different racial groups differ significantly in multiple aspects. Our goal is to
      systematically and comprehensively quantify racial differences in leukemia. The
      SEER database is analyzed, and comprehensive descriptive analysis is provided for
      the four major subtypes, namely ALL (acute lymphoblastic leukemia), CLL (chronic
      lymphoblastic leukemia), AML (acute myeloid leukemia), and CML (chronic myeloid
      leukemia), and for two age groups (<=14 and >14) separately. The racial groups
      studied include NHW (non-Hispanic White), HW (Hispanic White), BL (Black), and
      API (Asian and Pacific Islander). Univariate and multivariate analyses are
      conducted to quantify racial differences in patients' characteristics, incidence,
      and survival. For patients' characteristics, significant racial differences are
      observed in gender, age at diagnosis, diagnosis era, using radiation for
      treatment, registry, cancer history, and histology type. For incidence,
      significant racial differences are observed, and the patterns vary across
      subtypes, gender, and age groups. For most of the subtypes and gender and age
      groups, Blacks have the worst five-year survival, and significant racial
      differences exist. This study provides a comprehensive epidemiologic description
      of racial differences for the four major leukemia subtypes in the U.S.
      POPULATION: 

PMID- 29323236
TI  - Molecular determinants of Ca2+ sensitivity at the intersubunit interface of the
      BK channel gating ring.
AB  - The large-conductance calcium-activated K+ (BK) channel contains two
      intracellular tandem Ca2+-sensing RCK domains (RCK1 and RCK2), which tetramerize
      into a Ca2+ gating ring that regulates channel opening by conformational
      expansion in response to Ca2+ binding. Interestingly, the gating ring's
      intersubunit assembly interface harbors the RCK2 Ca2+-binding site, known as the
      Ca2+ bowl. The gating ring's assembly interface is made in part by intersubunit
      coordination of a Ca2+ ion between the Ca2+ bowl and an RCK1 Asn residue, N449,
      and by apparent intersubunit electrostatic interactions between E955 in RCK2 and
      R786 and R790 in the RCK2 of the adjacent subunit. To understand the role of the
      intersubunit assembly interface in Ca2+ gating, we performed mutational analyses
      of these putative interacting residues in human BK channels. We found that N449,
      despite its role in Ca2+ coordination, does not set the channel's Ca2+
      sensitivity, whereas E955 is a determinant of Ca2+ sensitivity, likely through
      intersubunit electrostatic interactions. Our findings provide evidence that the
      intersubunit assembly interface contains molecular determinants of Ca2+
      sensitivity in BK channels.

PMID- 29323238
TI  - Human complement receptor type 1 (CR1) protein levels and genetic variants in
      chronic Chagas Disease.
AB  - Complement is an essential element in both innate and acquired immunity
      contributing to the immunopathogenesis of many disorders, including Chagas
      Disease (CD). Human complement receptor 1 (CR1) plays a role in the clearance of
      complement opsonized molecules and may facilitate the entry of pathogens into
      host cells. Distinct CR1 exon 29 variants have been found associated with CR1
      expression levels, increased susceptibility and pathophysiology of several
      diseases. In this study, CR1 plasma levels were assessed by ELISA and CR1
      variants in exon 29 by sequencing in a Brazilian cohort of 232 chronic CD
      patients and 104 healthy controls. CR1 levels were significantly decreased in CD
      patients compared to controls (p < 0.0001). The CR1 rs1704660G, rs17047661G and
      rs6691117G variants were significantly associated with CD and in high linkage
      disequilibrium. The CR1*AGAGTG haplotype was associated with T. cruzi infection
      (p = 0.035, OR 3.99, CI 1.1-14.15) whereas CR1*AGGGTG was related to the risk of
      chagasic cardiomyopathy (p = 0.028, OR 12.15, CI 1.13-113). This is the first
      study that provides insights on the role of CR1 in development and clinical
      presentation of chronic CD.

PMID- 29323239
TI  - Specific Phospholipids Regulate the Acquisition of Neuronal and Astroglial
      Identities in Post-Mitotic Cells.
AB  - Hitherto, the known mechanisms underpinning cell-fate specification act on neural
      progenitors, affecting their commitment to generate neuron or glial cells. Here,
      we show that particular phospholipids supplemented in the culture media modify
      the commitment of post-mitotic neural cells in vitro. Phosphatidylcholine
      (PtdCho)-enriched media enhances neuronal differentiation at the expense of
      astroglial and unspecified cells. Conversely, phosphatidylethanolamine (PtdEtn)
      enhances astroglial differentiation and accelerates astrocyte maturation. The
      ability of phospholipids to modify the fate of post-mitotic cells depends on its
      presence during a narrow time-window during cell differentiation and it is
      mediated by the selective activation of particular signaling pathways. While
      PtdCho-mediated effect on neuronal differentiation depends on cAMP-dependent
      kinase (PKA)/calcium responsive element binding protein (CREB), PtdEtn stimulates
      astrogliogenesis through the activation of the MEK/ERK signaling pathway.
      Collectively, our results provide an additional degree of plasticity in neural
      cell specification and further support the notion that cell differentiation is a
      reversible phenomenon. They also contribute to our understanding of neuronal and
      glial lineage specification in the central nervous system, opening up new avenues
      to retrieve neurogenic capacity in the brain.

PMID- 29323240
TI  - Engineered 3D-printed artificial axons.
AB  - Myelination is critical for transduction of neuronal signals, neuron survival and
      normal function of the nervous system. Myelin disorders account for many
      debilitating neurological diseases such as multiple sclerosis and
      leukodystrophies. The lack of experimental models and tools to observe and
      manipulate this process in vitro has constrained progress in understanding and
      promoting myelination, and ultimately developing effective remyelination
      therapies. To address this problem, we developed synthetic mimics of neuronal
      axons, representing key geometric, mechanical, and surface chemistry components
      of biological axons. These artificial axons exhibit low mechanical stiffness
      approaching that of a human axon, over unsupported spans that facilitate
      engagement and wrapping by glial cells, to enable study of myelination in
      environments reflecting mechanical cues that neurons present in vivo. Our 3D
      printing approach provides the capacity to vary independently the complex
      features of the artificial axons that can reflect specific states of development,
      disease, or injury. Here, we demonstrate that oligodendrocytes' production and
      wrapping of myelin depend on artificial axon stiffness, diameter, and ligand
      coating. This biofidelic platform provides direct visualization and
      quantification of myelin formation and myelinating cells' response to both
      physical cues and pharmacological agents.

PMID- 29323241
TI  - Integrative approach using liver and duodenum RNA-Seq data identifies candidate
      genes and pathways associated with feed efficiency in pigs.
AB  - This study aims identifying candidate genes and pathways associated with feed
      efficiency (FE) in pigs. Liver and duodenum transcriptomes of 37 gilts showing
      high and low residual feed intake (RFI) were analysed by RNA-Seq. Gene expression
      data was explored through differential expression (DE) and weighted gene co
      expression network analyses. DE analysis revealed 55 and 112 differentially
      regulated genes in liver and duodenum tissues, respectively. Clustering genes
      according to their connectivity resulted in 23 (liver) and 25 (duodenum) modules
      of genes with a co-expression pattern. Four modules, one in liver (with 444 co
      expressed genes) and three in duodenum (gathering 37, 126 and 41 co-expressed
      genes), were significantly associated with FE indicators. Intra-module analyses
      revealed tissue-specific candidate genes; 12 of these genes were also identified
      as DE between individuals with high and low RFI. Pathways enriched by the list of
      genes showing DE and/or belonging to FE co-expressed modules included response to
      oxidative stress, inflammation, immune response, lipid metabolism and
      thermoregulation. Low overlapping between genes identified in duodenum and liver
      tissues was observed but heat shock proteins were associated to FE in both
      tissues. Our results suggest tissue-specific rather than common transcriptome
      regulatory processes associated with FE in pigs.

PMID- 29323242
TI  - Adipose-specific lipin1 overexpression in mice protects against alcohol-induced
      liver injury.
AB  - Excessive fatty acid release from the white adipose tissue (WAT) contributes to
      the development of alcoholic liver disease (ALD). Lipin1 (LPIN1), as a co
      regulator of DNA-bound transcription factors and a phosphatidic acid (PA)
      phosphatase (PAP) enzyme that dephosphorylates PA to form diacylglycerol (DAG),
      is dramatically reduced by alcohol in the WAT. This study aimed at determining
      the role of adipose LPIN1 in alcohol-induced lipodystrophy and the development of
      ALD. Transgenic mice overexpressing LPIN1 in adipose tissue (LPIN1-Tg) and wild
      type (WT) mice were fed a Lieber-DeCarli alcohol or isocaloric maltose dextrin
      control liquid diet for 8 weeks. Alcohol feeding to WT mice resulted in
      significant liver damage, which was significantly alleviated in the LPIN1-Tg
      mice. Alcohol feeding significantly reduced epididymal WAT (EWAT) mass, inhibited
      lipogenesis, and increased lipolysis in WT mice, which were attenuated in the
      LPIN1-Tg mice. LPIN1 overexpression also partially reversed alcohol-reduced
      plasma leptin levels. In WT mice, alcohol feeding induced hepatic lipid
      accumulation and down-regulation of beta-oxidation genes, which were dramatically
      alleviated in the LPIN1-Tg mice. LPIN1 overexpression also significantly
      attenuated alcohol-induced hepatic ER stress. These results suggest that
      overexpression of LPIN1 in adipose tissue restores WAT lipid storage function and
      secretive function to alleviate alcohol-induced liver injury.

PMID- 29323243
TI  - Expression of cry2Ah1 and two domain II mutants in transgenic tobacco confers
      high resistance to susceptible and Cry1Ac-resistant cotton bollworm.
AB  - To improve the novel Bacillus thuringiensis insecticidal gene cry2Ah1 toxicity,
      two mutants cry2Ah1-vp (V354VP) and cry2Ah1-sp (V354SP) were performed. SWISS
      MODEL analysis showed two mutants had a longer loop located between beta-4 and
      beta-5 of domain II, resulting in higher binding affinity with brush border
      membrane vesicles (BBMV) of Helicoverpa armigera comparing with Cry2Ah1. The
      cry2Ah1, cry2Ah1-vp, and cry2Ah1-sp were optimized codon usage according to plant
      codon bias, and named mcry2Ah1, mcry2Ah1-vp, and mcry2Ah1-sp. They were
      transformed into tobacco via Agrobacterium-mediated transformation and a total of
      4, 8, and 24 transgenic tobacco plants were obtained, respectively. The molecular
      detection showed the exogenous gene was integrated into tobacco genome, and
      successfully expressed at the transcript and translation levels. Cry2Ah1 protein
      in transgenic tobacco plants varied from 4.41 to 40.28 MUg g-1 fresh weight.
      Insect bioassays indicated that all transgenic tobacco plants were highly toxic
      to both susceptible and Cry1Ac-resistant cotton bollworm larvae, and the insect
      resistance efficiency to Cry1Ac-resistant cotton bollworm was highest in mcry2Ah1
      sp transgenic tobacco plants. The results demonstrated that cry2Ah1 was a useful
      Bt insecticidal gene to susceptible and Cry1Ac-resistant cotton bollworm and had
      potential application for insect biocontrol and as a candidate for pyramid
      strategy in Bt crops.

PMID- 29323244
TI  - Validity of Valence Estimation of Dopants in Glasses using XANES Analysis.
AB  - X-ray absorption near edge structure (XANES) measurement is one of the most
      powerful tools for the evaluation of a cation valence state. XANES measurement is
      sometimes the only available technique for the evaluation of the valence state of
      a dopant cation, which often occurs in phosphor materials. The validity of the
      core excitation process should be examined as a basis for understanding the
      applicability of this technique. Here, we demonstrate the validity of valence
      estimation of tin in oxide glasses, using Sn K-edge and L-edge XANES spectra, and
      compare the results with 119Sn Mossbauer analysis. The results of Sn K-edge XANES
      spectra analysis reveal that this approach cannot evaluate the actual valence
      state. On the contrary, in LII-edge absorption whose transition is 2p1/2-d, the
      change of the white line corresponds to the change of the valence state of tin,
      which is calculated from the 119Sn Mossbauer spectra. Among several analytical
      approaches, valence evaluation using the peak area, such as the absorption edge
      energy E 0 at the fractions of the edge step or E 0 at the zero of the second
      derivative, is better. The observed findings suggest that the valence state of a
      heavy element in amorphous materials should be discussed using several different
      definitions with error bars, even though L-edge XANES analyses are used.

PMID- 29323245
TI  - Author Correction: Multiple similarly effective solutions exist for biomedical
      feature selection and classification problems.
AB  - A correction to this article has been published and is linked from the HTML
      version of this paper. The error has been fixed in the paper.

PMID- 29323246
TI  - ModuleDiscoverer: Identification of regulatory modules in protein-protein
      interaction networks.
AB  - The identification of disease-associated modules based on protein-protein
      interaction networks (PPINs) and gene expression data has provided new insights
      into the mechanistic nature of diverse diseases. However, their identification is
      hampered by the detection of protein communities within large-scale, whole-genome
      PPINs. A presented successful strategy detects a PPIN's community structure based
      on the maximal clique enumeration problem (MCE), which is a non-deterministic
      polynomial time-hard problem. This renders the approach computationally
      challenging for large PPINs implying the need for new strategies. We present
      ModuleDiscoverer, a novel approach for the identification of regulatory modules
      from PPINs and gene expression data. Following the MCE-based approach,
      ModuleDiscoverer uses a randomization heuristic-based approximation of the
      community structure. Given a PPIN of Rattus norvegicus and public gene expression
      data, we identify the regulatory module underlying a rodent model of non
      alcoholic steatohepatitis (NASH), a severe form of non-alcoholic fatty liver
      disease (NAFLD). The module is validated using single-nucleotide polymorphism
      (SNP) data from independent genome-wide association studies and gene enrichment
      tests. Based on gene enrichment tests, we find that ModuleDiscoverer performs
      comparably to three existing module-detecting algorithms. However, only our NASH
      module is significantly enriched with genes linked to NAFLD-associated SNPs.
      ModuleDiscoverer is available at http://www.hki-jena.de/index.php/0/2/490
      (Others/ModuleDiscoverer).

PMID- 29323247
TI  - Leakage correction improves prognosis prediction of dynamic susceptibility
      contrast perfusion MRI in primary central nervous system lymphoma.
AB  - To evaluate whether the cerebral blood volume (CBV) measurement with leakage
      correction from dynamic susceptibility contrast perfusion weighted imaging can be
      useful in predicting prognosis for primary central nervous system lymphoma
      (PCNSL). 46 PCNSL patients were included and classified by radiation therapy (RT)
      stratification into RT (n = 30) and non-RT (n = 16) groups. The corresponding
      histogram parameters of normalized CBV (nCBV) maps with or without leakage
      correction were calculated on contrast-enhanced T1 weighted image (CE T1WI) or on
      fluid attenuated inversion recovery image. The 75th percentile nCBV with leakage
      correction based on CE T1WI (T1 nCBVL75%) had a significant difference between
      the short and long progression free survival (PFS) subgroups of the RT group and
      the non-RT group, respectively. Based on the survival analysis, patients in the
      RT group with high T1 nCBVL75% had earlier progression than the others with a low
      T1 nCBVL75%. However, patients in the non-RT group with a high T1 nCBVL75% had
      slower progression than the others with a low T1 nCBVL75%. Based on RT
      stratification, the CBV with leakage correction has potential as a noninvasive
      biomarker for the prognosis prediction of PCNSL to identify high risk patients
      and it has a different correlation with the PFS based on the presence of combined
      RT.

PMID- 29323248
TI  - Exploring the utility of alcohol flushing as an instrumental variable for alcohol
      intake in Koreans.
AB  - Previous studies have indicated an association of higher alcohol intake with
      cardiovascular disease and related traits, but causation has not been
      definitively established. In this study, the causal effect of alcohol intake on
      hypertension in 2,011 men and women from the Ansan-Ansung cohort was estimated
      using an instrumental variable (IV) approach, with both a phenotypic and
      genotypic instrument for alcohol intake: alcohol flushing and the rs671 genotype
      (in the alcohol dehydrogenase 2 [ALDH2] gene), respectively. Both alcohol
      flushing and the rs671 genotype were associated with alcohol intake (difference
      in alcohol intake with alcohol flushers vs. non-flushers: -9.07 g/day; 95%
      confidence interval [CI]: -11.12, -7.02; P-value: 8.3 * 10-18 and with the rs671
      GA + AA vs. GG genotype: -7.94 g/day; 95% CI: -10.20, -5.69; P-value: 6.1 * 10
      12). An increase in alcohol intake, as predicted by both the absence of alcohol
      flushing and the presence of the rs671 GG genotype in the IV analyses, was
      associated with an increase in blood pressure in men from this Korean population.
      In conclusion, this study supports a causal effect of alcohol intake on
      hypertension and indicated that alcohol flushing may be a valid proxy for the
      ALDH2 rs671 polymorphism, which influences alcohol intake in this Korean
      population.

PMID- 29323250
TI  - A biofilm and organomineralisation model for the growth and limiting size of
      ooids.
AB  - Ooids are typically spherical sediment grains characterised by concentric layers
      encapsulating a core. There is no universally accepted explanation for ooid
      genesis, though factors such as agitation, abiotic and/or microbial
      mineralisation and size limitation have been variously invoked. Here we examine
      the possible influence of microbial organomineralisation on the formation of some
      naturally occurring ooids. We develop a mathematical model for ooid growth,
      inspired by work on avascular brain tumours, that assumes mineralisation in a
      biofilm to form a central core which then nucleates the progressive growth of
      concentric laminations. The model predicts a limiting size with the sequential
      width variation of growth rings comparing favourably with those observed in
      experimentally grown ooids generated from biomicrospheres. In reality, this model
      pattern may be complicated during growth by syngenetic aggrading neomorphism of
      the unstable mineral phase, followed by diagenetic recrystallisation that further
      complicates the structure. Our model provides a potential key to understanding
      the genetic archive preserved in the internal structures of some ooids.

PMID- 29323249
TI  - Probabilistic data integration identifies reliable gametocyte-specific proteins
      and transcripts in malaria parasites.
AB  - Plasmodium gametocytes are the sexual forms of the malaria parasite essential for
      transmission to mosquitoes. To better understand how gametocytes differ from
      asexual blood-stage parasites, we performed a systematic analysis of available
      'omics data for P. falciparum and other Plasmodium species. 18 transcriptomic and
      proteomic data sets were evaluated for the presence of curated "gold standards"
      of 41 gametocyte-specific versus 46 non-gametocyte genes and integrated using
      Bayesian probabilities, resulting in gametocyte-specificity scores for all P.
      falciparum genes. To illustrate the utility of the gametocyte score, we explored
      newly predicted gametocyte-specific genes as potential biomarkers of gametocyte
      carriage and exposure. We analyzed the humoral immune response in field samples
      against 30 novel gametocyte-specific antigens and found five antigens to be
      differentially recognized by gametocyte carriers as compared to malaria-infected
      individuals without detectable gametocytes. We also validated the gametocyte
      specificity of 15 identified gametocyte transcripts on culture material and
      samples from naturally infected individuals, resulting in eight transcripts that
      were >1000-fold higher expressed in gametocytes compared to asexual parasites and
      whose transcript abundance allowed gametocyte detection in naturally infected
      individuals. Our integrated genome-wide gametocyte-specificity scores provide a
      comprehensive resource to identify targets and monitor P. falciparum
      gametocytemia.

PMID- 29323251
TI  - Vitamin E inhibits the UVAI induction of "light" and "dark" cyclobutane
      pyrimidine dimers, and oxidatively generated DNA damage, in keratinocytes.
AB  - Solar ultraviolet radiation (UVR)-induced DNA damage has acute, and long-term
      adverse effects in the skin. This damage arises directly by absorption of UVR,
      and indirectly via photosensitization reactions. The aim of the present study was
      to assess the effects of vitamin E on UVAI-induced DNA damage in keratinocytes in
      vitro. Incubation with vitamin E before UVAI exposure decreased the formation of
      oxidized purines (with a decrease in intracellular oxidizing species), and
      cyclobutane pyrimidine dimers (CPD). A possible sunscreening effect was excluded
      when similar results were obtained following vitamin E addition after UVAI
      exposure. Our data showed that DNA damage by UVA-induced photosensitization
      reactions can be inhibited by the introduction of vitamin E either pre- or post
      irradiation, for both oxidized purines and CPD (including so-called "dark" CPDs).
      These data validate the evidence that some CPD are induced by UVAI initially via
      photosensitization, and some via chemoexcitation, and support the evidence that
      vitamin E can intervene in this pathway to prevent CPD formation in
      keratinocytes. We propose the inclusion of similar agents into topical sunscreens
      and aftersun preparations which, for the latter in particular, represents a means
      to mitigate on-going DNA damage formation, even after sun exposure has ended.

PMID- 29323252
TI  - Clinical Value of 99mTc-3PRGD2 SPECT/CT in Differentiated Thyroid Carcinoma with
      Negative 131I Whole-Body Scan and Elevated Thyroglobulin Level.
AB  - The aim of this study was to assess the usefulness of integrin imaging with 99mTc
      PEG4-E[PEG4-c(RGDfK)]2 (99mTc-3PRGD2) single photon emission computed tomography
      (SPECT)/computed tomography (CT) in detecting recurrent disease in patients with
      differentiated thyroid cancer (DTC), negative radioiodine whole-body scan (WBS)
      and high serum thyroglobulin (Tg). Thirty-seven patients who underwent total
      thyroidectomy followed by radioactive iodine ablation and had negative
      radioiodine WBS but elevated Tg levels were included. 99mTc-3PRGD2 SPECT/CT was
      performed 1 week after the negative diagnostic 131I WBS. Diagnostic performance
      indicators, including sensitivity, specificity, positive predictive value (PPV),
      and negative predictive value (NPV), for 99mTc-3PRGD2 SPECT/CT was calculated.
      The correlations between SPECT/CT results and clinic-pathological characteristics
      were examined. In 30 (81.1%) of the 37 patients, 99mTc-3PRGD2 SPECT/CT showed
      positive uptake. The sensitivity, specificity, PPV, and NPV of SPECT/CT to detect
      recurrent disease at follow-up were 96.6%, 75%, 93.3% and 85.7%, respectively.
      The sensitivity and PPV of SPECT/CT increased with increasing serum Tg levels.
      99mTc-3PRGD2 SPECT/CT showed high sensitivity and PPV in the detection of
      recurrence among DTC patients with higher Tg levels and negative WBS, and the
      probability of obtaining a positive SPECT/CT result was related with the level of
      Tg.

PMID- 29323253
TI  - Assessing kinetic fractionation in brachiopod calcite using clumped isotopes.
AB  - Brachiopod shells are the most widely used geological archive for the
      reconstruction of the temperature and the oxygen isotope composition of
      Phanerozoic seawater. However, it is not conclusive whether brachiopods
      precipitate their shells in thermodynamic equilibrium. In this study, we
      investigated the potential impact of kinetic controls on the isotope composition
      of modern brachiopods by measuring the oxygen and clumped isotope compositions of
      their shells. Our results show that clumped and oxygen isotope compositions
      depart from thermodynamic equilibrium due to growth rate-induced kinetic effects.
      These departures are in line with incomplete hydration and hydroxylation of
      dissolved CO2. These findings imply that the determination of taxon-specific
      growth rates alongside clumped and bulk oxygen isotope analyses is essential to
      ensure accurate estimates of past ocean temperatures and seawater oxygen isotope
      compositions from brachiopods.

PMID- 29323255
TI  - Counting statistics of photon emissions detected in non-Markovian environment.
AB  - In this work we present a large-deviation analysis for the counting statistics of
      atomic spontaneous emissions continuously detected in finite-bandwidth non
      Markovian environment. We show that the statistics of the spontaneous emissions
      depends on the time interval (tau) of successive detections, which can result in
      big differences such as dynamical phase transition. This feature excludes the
      idea of regarding the spontaneous emissions as detection-free objective events.
      Possible experiment is briefly discussed in connection with the state-of-the-art
      optical cavity set-up.

PMID- 29323254
TI  - Genome-wide association study reveals candidate genes influencing lipids and
      diterpenes contents in Coffea arabica L.
AB  - Lipids, including the diterpenes cafestol and kahweol, are key compounds that
      contribute to the quality of coffee beverages. We determined total lipid content
      and cafestol and kahweol concentrations in green beans and genotyped 107 Coffea
      arabica accessions, including wild genotypes from the historical FAO collection
      from Ethiopia. A genome-wide association study was performed to identify genomic
      regions associated with lipid, cafestol and kahweol contents and cafestol/kahweol
      ratio. Using the diploid Coffea canephora genome as a reference, we identified
      6,696 SNPs. Population structure analyses suggested the presence of two to three
      groups (K = 2 and K = 3) corresponding to the east and west sides of the Great
      Rift Valley and an additional group formed by wild accessions collected in
      western forests. We identified 5 SNPs associated with lipid content, 4 with
      cafestol, 3 with kahweol and 9 with cafestol/kahweol ratio. Most of these SNPs
      are located inside or near candidate genes related to metabolic pathways of these
      chemical compounds in coffee beans. In addition, three trait-associated SNPs
      showed evidence of directional selection among cultivated and wild coffee
      accessions. Our results also confirm a great allelic richness in wild accessions
      from Ethiopia, especially in accessions originating from forests in the west side
      of the Great Rift Valley.

PMID- 29323256
TI  - Splicing of platelet resident pre-mRNAs upon activation by physiological stimuli
      results in functionally relevant proteome modifications.
AB  - Platelet activation triggers thrombus formation in physiological and pathological
      conditions, such as acute coronary syndromes. Current therapies still fail to
      prevent thrombotic events in numerous patients, indicating that the mechanisms
      modulating platelet response during activation need to be clarified. The evidence
      that platelets are capable of de novo protein synthesis in response to stimuli
      raised the issue of how megakaryocyte-derived mRNAs are regulated in these
      anucleate cell fragments. Proteogenomics was applied here to investigate this
      phenomeon in platelets activated in vitro with Collagen or Thrombin Receptor
      Activating Peptide. Combining proteomics and transcriptomics allowed in depth
      platelet proteome characterization, revealing a significant effect of either
      stimulus on proteome composition. In silico analysis revealed the presence of
      resident immature RNAs in resting platelets, characterized by retained introns,
      while unbiased proteogenomics correlated intron removal by RNA splicing with
      changes on proteome composition upon activation. This allowed identification of a
      set of transcripts undergoing maturation by intron removal during activation and
      resulting in accumulation of the corresponding peptides at exon-exon junctions.
      These results indicate that RNA splicing events occur in platelets during
      activation and that maturation of specific pre-mRNAs is part of the activation
      cascade, contributing to a dynamic fine-tuning of the transcriptome.

PMID- 29323257
TI  - Dengue virus-induced ER stress is required for autophagy activation, viral
      replication, and pathogenesis both in vitro and in vivo.
AB  - Dengue virus (DENV) utilizes the endoplasmic reticulum (ER) for replication and
      assembling. Accumulation of unfolded proteins in the ER lumen leads to ER stress
      and unfolded protein response (UPR). Three branches of UPRs temporally modulated
      DENV infection. Moreover, ER stress can also induce autophagy. DENV infection
      induces autophagy which plays a promotive role in viral replication has been
      reported. However, the role of ER stress in DENV-induced autophagy, viral titer,
      and pathogenesis remain unclear. Here, we reveal that ER stress and its
      downstream UPRs are indispensable for DENV-induced autophagy in various human
      cells. We demonstrate that PERK-eIF2alpha and IRE1alpha-JNK signaling pathways
      increased autophagy and viral load after DENV infection. However, ATF6-related
      pathway showed no effect on autophagy and viral replication. IRE1alpha-JNK
      downstream molecule Bcl-2 was phosphorylated by activated JNK and dissociated
      from Beclin 1, which playing a critical role in autophagy activation. These
      findings were confirmed as decreased viral titer, attenuated disease symptoms,
      and prolonged survival rate in the presence of JNK inhibitor in vivo. In summary,
      we are the first to reveal that DENV2-induced ER stress increases autophagy
      activity, DENV replication, and pathogenesis through two UPR signaling pathways
      both in vitro and in vivo.

PMID- 29323258
TI  - Association between arsenic metabolism gene polymorphisms and arsenic-induced
      skin lesions in individuals exposed to high-dose inorganic arsenic in northwest
      China.
AB  - Individuals in a given environment contaminated with arsenic have different
      susceptibilities to disease, which may be related to arsenic metabolism, age,
      gender, genetics and other factors. This study recruited 850 subjects, including
      331 cases and 519 controls, from populations exposed to high levels of arsenic in
      drinking water in northwest China. Genotypes were determined using a custom-by
      design 48-Plex SNPscanTM kit. The results indicated that subjects who carried at
      least one C allele for GSTO1 rs11191979 polymorphism, at least one A allele for
      GSTO1 rs2164624, at least one A allele for GSTO1 rs4925, the AG genotype for
      GSTO2 rs156697, the AG genotype or at least one G allele for GSTO2 rs2297235 or
      the GG genotype or at least one G allele for PNP rs3790064 had an increased risk
      of arsenic-related skin lesions. In addition, the haplotype CT between rs4925 and
      rs11191979 appeared to confer a high risk of arsenic-included skin lesions (OR =
      1.377, 95% CI = 1.03-1.84), as did the haplotype GCG among rs156697, rs157077 and
      rs2297235 (OR = 2.197, 95% CI = 1.08-4.44). The results showed that the variants
      of GSTO1, GSTO2 and PNP render the susceptible toward developing arsenic-induced
      skin lesions in individuals exposed to high-dose inorganic arsenic in northwest
      China.

PMID- 29323259
TI  - Impacts of feeding preweaned calves milk containing drug residues on the
      functional profile of the fecal microbiota.
AB  - Feeding drug residue-containing milk to calves is common worldwide and no
      information is currently available on the impact on the functional profile of the
      fecal microbiota. Our objective was to characterize the functional profile of the
      fecal microbiota of preweaned dairy calves fed raw milk with residual
      concentrations of antimicrobials commonly found in waste milk from birth to
      weaning. Calves were assigned to a controlled feeding trial being fed milk with
      no drug residues or milk with antibiotic residues. Fecal samples collected from
      each calf once a week starting at birth, prior to the first feeding in the trial,
      until 6 weeks of age. Antibiotic residues resulted in a significant difference in
      relative abundance of microbial cell functions, especially with genes linked with
      stress response, regulation and cell signaling, and nitrogen metabolism. These
      changes could directly impacts selection and dissemination of virulence and
      antimicrobial. Our data also identified a strong association between age in weeks
      and abundance of Resistance to Antibiotics and Toxic Compounds. Findings from
      this study support the hypothesis that drug residues, even at very low
      concentrations, impact the gut microbiota of calves and result in changes in the
      functional profile of microbial populations.

PMID- 29323260
TI  - Dietary fatty acids sex-specifically modulate guinea pig postnatal development
      via cortisol concentrations.
AB  - Early ontogenetic periods and postnatal maturation in organisms are sex
      specifically sensitive to hypothalamic-pituitary-adrenal (HPA)-axis activities,
      related glucocorticoid secretions, and their effects on energy balance and
      homeostasis. Dietary polyunsaturated (PUFAs) and saturated (SFAs) fatty acids
      potentially play a major role in this context because PUFAs positively affect HPA
      axis functions and a shift towards SFAs may impair body homeostasis. Here we show
      that dietary PUFAs positively affect postnatal body mass gain and diminish
      negative glucocorticoid-effects on structural growth rates in male guinea pigs.
      In contrast, SFAs increased glucocorticoid concentrations, which positively
      affected testes size and testosterone concentrations in males, but limited their
      body mass gain and first year survival rate. No distinct diet-related effects
      were detectable on female growth rates. These results highlight the importance of
      PUFAs in balancing body homeostasis during male's juvenile development, which
      clearly derived from a sex-specific energetic advantage of dietary PUFA intakes
      compared to SFAs.

PMID- 29323261
TI  - Neoadjuvant therapy in relation to lymphadenectomy and resection margins during
      surgery for oesophageal cancer.
AB  - Differences in lymph node yield and tumour-involved resection margins comparing
      neoadjuvant therapy plus surgery with surgery alone for oesophageal cancer are
      unclear. Patients who underwent oesophageal cancer surgery in Sweden in 1987-2010
      were included. Patients treated with neoadjuvant therapy were compared with those
      who underwent surgery alone. Outcomes were the number of examined lymph nodes
      (main outcome), number metastatic lymph nodes, and resection margin status. Rate
      ratios (RRs) and 95% CIs of lymph node yield were calculated by Poisson
      regression, and odds ratios (ORs) and 95% CIs of resection margin status by
      multivariable logistic regression, both adjusted for confounders. Among 1818
      patients, 587 (32%) had received neoadjuvant therapy and 1231 (68%) had not.
      Lymph node yield was lower in the neoadjuvant therapy group (median 6 versus 8;
      adjusted RR 0.75, 0.73-0.78). Fewer metastatic nodes were identified following
      neoadjuvant therapy (median 0 versus 1; adjusted RR 0.76, 0.69-0.84). Neoadjuvant
      therapy associated to decreased risk of tumour-involved resection margins when
      adjusted for confounders except T-stage (OR 0.52, 0.38-0.70), but the association
      did not remain after adjustment for T-stage (OR 0.91, 0.64-1.29). Neoadjuvant
      therapy seems to decrease the lymph node yield and decrease the risk of tumour
      involved resection margins by shrinking primary tumour.

PMID- 29323262
TI  - Cooperative standing-horizontal-standing reentrant transition for numerous solid
      particles under external vibration.
AB  - We report the collective behavior of numerous plastic bolt-like particles
      exhibiting one of two distinct states, either standing stationary or horizontal
      accompanied by tumbling motion, when placed on a horizontal plate undergoing
      sinusoidal vertical vibration. Experimentally, we prepared an initial state in
      which all of the particles were standing except for a single particle that was
      placed at the center of the plate. Under continuous vertical vibration, the
      initially horizontal particle triggers neighboring particles to fall over into a
      horizontal state through tumbling-induced collision, and this effect gradually
      spreads to all of the particles, i.e., the number of horizontal particles is
      increased. Interestingly, within a certain range of vibration intensity, almost
      all of the horizontal particles revert back to standing in association with the
      formation of apparent 2D hexagonal dense-packing. Thus, phase segregation between
      high and low densities, or crystalline and disperse domains, of standing
      particles is generated as a result of the reentrant transition. The essential
      features of such cooperative dynamics through the reentrant transition are
      elucidated with a simple kinetic model. We also demonstrate that an excitable
      wave with the reentrant transition is observed when particles are situated in a
      quasi-one-dimensional confinement on a vibrating plate.

PMID- 29323263
TI  - Putative sex pheromone of the Asian citrus psyllid, Diaphorina citri, breaks down
      into an attractant.
AB  - Under laboratory conditions, mating activity in Asian citrus psyllid (ACP)
      started 4 days after emergence, peaked at day 7, and showed a clear window of
      activity starting 8 h into the photophase and extending through the first hour of
      the scotophase. We confirmed that ACP males are attracted to emanations from
      conspecific females. Traps loaded with a candidate compound enriched with female
      extract, lignoceryl acetate (24Ac), at various doses were active only after being
      deployed for several weeks in the field, suggesting that a degradation product,
      not the test compound, was the active ingredient(s). Lignocerol, a possible
      product of 24Ac degradation, was not active, whereas acetic acid, another
      possible degradation product, was found in the airborne volatile collections from
      lures matured under field conditions and detected in higher amounts in volatiles
      collected from females at the peak of mating activity than in male samples.
      Acetic acid elicited dose-dependent electroantennographic responses and attracted
      ACP males, but not females, in Y-type and 4-way olfactometers. Field tests showed
      that acetic acid-baited traps captured significantly more males than control
      traps. Surprisingly, captures of females in acetic acid-baited traps were also
      higher than in control traps, possibly because of physical stimuli emitted by
      captured males.

PMID- 29323264
TI  - Orai3 calcium channel and resistance to chemotherapy in breast cancer cells: the
      p53 connection.
AB  - Orai proteins are highly selective calcium channels playing an important role in
      calcium entry. Orai3 channels are overexpressed in breast cancer (BC) tissues,
      and involved in their proliferation, cell cycle progression and survival. Herein,
      we sought to address the involvement of Orai3 in resistance to chemotherapeutic
      drugs. Using high-throughput approaches, we investigated major changes induced by
      Orai3 overexpression, including downstream signaling mechanisms involved in BC
      chemotherapy resistance. Resistance was dependent on external calcium presence
      and thus Orai3 functionality. This effect allowed a downregulation of the p53
      tumor suppressor protein expression via the pro-survival PI3K/Sgk-1/Sek-1
      pathway. We demonstrated that p53 degradation occurred not only via Mdm2, but
      also via another unexpected E3 ubiquitin ligase, Nedd4-2. We found supporting
      bioinformatic evidence linking Orai3 overexpression and chemoresistance in large
      human BC data sets. Altogether, our results shed light on the molecular
      mechanisms activated in BC cells commonly found to overexpress Orai3, allowing
      resistance to chemotherapeutic drugs.

PMID- 29323265
TI  - Redox-dependent BMI1 activity drives in vivo adult cardiac progenitor cell
      differentiation.
AB  - Accumulation of reactive oxygen species (ROS) is associated with several
      cardiovascular pathologies and with cell cycle exit by neonanatal cardiomyocytes,
      a key limiting factor in the regenerative capacity of the adult mammalian heart.
      The polycomb complex component BMI1 is linked to adult progenitors and is an
      important partner in DNA repair and redox regulation. We found that high BMI1
      expression is associated with an adult Sca1+ cardiac progenitor sub-population
      with low ROS levels. In homeostasis, BMI1 repressed cell fate genes, including a
      cardiogenic differentiation program. Oxidative damage nonetheless modified BMI1
      activity in vivo by derepressing canonical target genes in favor of their
      antioxidant and anticlastogenic functions. This redox-mediated mechanism is not
      restricted to damage situations, however, and we report ROS-associated
      differentiation of cardiac progenitors in steady state. These findings
      demonstrate how redox status influences the cardiac progenitor response, and
      identify redox-mediated BMI1 regulation with implications in maintenance of
      cellular identity in vivo.

PMID- 29323266
TI  - AIF loss deregulates hematopoiesis and reveals different adaptive metabolic
      responses in bone marrow cells and thymocytes.
AB  - Mitochondrial metabolism is a tightly regulated process that plays a central role
      throughout the lifespan of hematopoietic cells. Herein, we analyze the
      consequences of the mitochondrial oxidative phosphorylation (OXPHOS)/metabolism
      disorder associated with the cell-specific hematopoietic ablation of apoptosis
      inducing factor (AIF). AIF-null (AIF-/Y ) mice developed pancytopenia that was
      associated with hypocellular bone marrow (BM) and thymus atrophy. Although
      myeloid cells were relatively spared, the B-cell and erythroid lineages were
      altered with increased frequencies of precursor B cells, pro-erythroblasts I, and
      basophilic erythroblasts II. T-cell populations were dramatically reduced with a
      thymopoiesis blockade at a double negative (DN) immature state, with DN1
      accumulation and delayed DN2/DN3 and DN3/DN4 transitions. In BM cells, the
      OXPHOS/metabolism dysfunction provoked by the loss of AIF was counterbalanced by
      the augmentation of the mitochondrial biogenesis and a shift towards anaerobic
      glycolysis. Nevertheless, in a caspase-independent process, the resulting excess
      of reactive oxygen species compromised the viability of the hematopoietic stem
      cells (HSC) and progenitors. This led to the progressive exhaustion of the HSC
      pool, a reduced capacity of the BM progenitors to differentiate into colonies in
      methylcellulose assays, and the absence of cell-autonomous HSC repopulating
      potential in vivo. In contrast to BM cells, AIF-/Y thymocytes compensated for the
      OXPHOS breakdown by enhancing fatty acid beta-oxidation. By over-expressing CPT1,
      ACADL and PDK4, three key enzymes facilitating fatty acid beta-oxidation (e.g.,
      palmitic acid assimilation), the AIF-/Y thymocytes retrieved the ATP levels of
      the AIF +/Y cells. As a consequence, it was possible to significantly reestablish
      AIF-/Y thymopoiesis in vivo by feeding the animals with a high-fat diet
      complemented with an antioxidant. Overall, our data reveal that the mitochondrial
      signals regulated by AIF are critical to hematopoietic decision-making. Emerging
      as a link between mitochondrial metabolism and hematopoietic cell fate, AIF
      mediated OXPHOS regulation represents a target for the development of new
      immunomodulatory therapeutics.

PMID- 29323269
TI  - Postmitotic nuclear pore assembly proceeds by radial dilation of small membrane
      openings.
AB  - The nuclear envelope has to be reformed after mitosis to create viable daughter
      cells with closed nuclei. How membrane sealing of DNA and assembly of nuclear
      pore complexes (NPCs) are achieved and coordinated is poorly understood. Here, we
      reconstructed nuclear membrane topology and the structures of assembling NPCs in
      a correlative 3D EM time course of dividing human cells. Our quantitative
      ultrastructural analysis shows that nuclear membranes form from highly
      fenestrated ER sheets whose holes progressively shrink. NPC precursors are found
      in small membrane holes and dilate radially during assembly of the inner ring
      complex, forming thousands of transport channels within minutes. This mechanism
      is fundamentally different from that of interphase NPC assembly and explains how
      mitotic cells can rapidly establish a closed nuclear compartment while making it
      transport competent.

PMID- 29323268
TI  - Evaluation of animal-to-human and human-to-human transmission of influenza A
      (H7N9) virus in China, 2013-15.
AB  - A novel avian-origin influenza A(H7N9) virus emerged in China in March 2013 and
      by 27 September 2017 a total of 1533 laboratory-confirmed cases have been
      reported. Occurrences of animal-to-human and human-to-human transmission have
      been previously identified, and the force of human-to-human transmission is an
      important component of risk assessment. In this study, we constructed an
      ecological model to evaluate the animal-to-human and human-to-human transmission
      of H7N9 during the first three epidemic waves in spring 2013, winter/spring 2013
      2014 and winter/spring 2014-2015 in China based on 149 laboratory-confirmed urban
      cases. Our analysis of patterns in incidence in major cities allowed us to
      estimate a mean incubation period in humans of 2.6 days (95% credibility
      interval, CrI: 1.4-3.1) and an effective reproduction number Re of 0.23 (95% CrI:
      0.05-0.47) for the first wave, 0.16 (95% CrI: 0.01-0.41) for the second wave, and
      0.16 (95% CrI: 0.01-0.45) for the third wave without a significant difference
      between waves. There was a significant decrease in the incidence of H7N9 cases
      after live poultry market closures in various major cities. Our analytic
      framework can be used for continued assessment of the risk of human to human
      transmission of A(H7N9) virus as human infections continue to occur in China.

PMID- 29323267
TI  - Scaffold-free generation of uniform adipose spheroids for metabolism research and
      drug discovery.
AB  - Adipose tissue dysfunction is critical to the development of type II diabetes and
      other metabolic diseases. While monolayer cell culture has been useful for
      studying fat biology, 2D culture often does not reflect the complexity of fat
      tissue. Animal models are also problematic in that they are expensive, time
      consuming, and may not completely recapitulate human biology because of species
      variation. To address these problems, we have developed a scaffold-free method to
      generate 3D adipose spheroids from primary or immortal human or mouse pre
      adipocytes. Pre-adipocytes self-organize into spheroids in hanging drops and upon
      transfer to low attachment plates, can be maintained in long-term cultures. Upon
      exposure to differentiation cues, the cells mature into adipocytes, accumulating
      large lipid droplets that expand with time. The 3D spheroids express and secrete
      higher levels of adiponectin compared to 2D culture and respond to stress, either
      culture-related or toxin-associated, by secreting pro-inflammatory adipokines. In
      addition, 3D spheroids derived from brown adipose tissue (BAT) retain expression
      of BAT markers better than 2D cultures derived from the same tissue. Thus, this
      model can be used to study both the maturation of pre-adipocytes or the function
      of mature adipocytes in a 3D culture environment.

PMID- 29323270
TI  - Two three-strand intermediates are processed during Rad51-driven DNA strand
      exchange.
AB  - During homologous recombination, Rad51 forms a nucleoprotein filament with single
      stranded DNA (ssDNA) that undergoes strand exchange with homologous double
      stranded DNA (dsDNA). Here, we use real-time analysis to show that strand
      exchange by fission yeast Rad51 proceeds via two distinct three-strand
      intermediates, C1 and C2. Both intermediates contain Rad51, but whereas the donor
      duplex remains intact in C1, the ssDNA strand is intertwined with the
      complementary strand of the donor duplex in C2. Swi5-Sfr1, an evolutionarily
      conserved recombination activator, facilitates the C1-C2 transition and
      subsequent ssDNA release from C2 to complete strand exchange in an ATP-hydrolysis
      dependent manner. In contrast, Ca2+, which activates the Rad51 filament by
      curbing ATP hydrolysis, facilitates the C1-C2 transition but does not promote
      strand exchange. These results reveal that Swi5-Sfr1 and Ca2+ have different
      activation modes in the late synaptic phase, despite their common function in
      stabilizing the presynaptic filament.

PMID- 29323271
TI  - Cryo-EM structures of the human INO80 chromatin-remodeling complex.
AB  - Access to chromatin for processes such as transcription and DNA repair requires
      the sliding of nucleosomes along DNA. This process is aided by chromatin
      remodeling complexes, such as the multisubunit INO80 chromatin-remodeling
      complex. Here we present cryo-EM structures of the active core complex of human
      INO80 at 9.6 A, with portions at 4.1-A resolution, and reconstructions of
      combinations of subunits. Together, these structures reveal the architecture of
      the INO80 complex, including Ino80 and actin-related proteins, which is assembled
      around a single RUVBL1 (Tip49a) and RUVBL2 (Tip49b) AAA+ heterohexamer. An
      unusual spoked-wheel structural domain of the Ino80 subunit is engulfed by this
      heterohexamer; both, in combination, form the core of the complex. We also
      identify a cleft in RUVBL1 and RUVBL2, which forms a major interaction site for
      partner proteins and probably communicates these interactions to its nucleotide
      binding sites.

PMID- 29323273
TI  - Histone octamer rearranges to adapt to DNA unwrapping.
AB  - Nucleosomes, the basic units of chromatin, package and regulate expression of
      eukaryotic genomes. Although the structure of the intact nucleosome is well
      characterized, little is known about structures of partially unwrapped, transient
      intermediates. In this study, we present nine cryo-EM structures of distinct
      conformations of nucleosome and subnucleosome particles. These structures show
      that initial DNA breathing induces conformational changes in the histone octamer,
      particularly in histone H3, that propagate through the nucleosome and prevent
      symmetrical DNA opening. Rearrangements in the H2A-H2B dimer strengthen
      interaction with the unwrapping DNA and promote nucleosome stability. In
      agreement with this, cross-linked H2A-H2B that cannot accommodate unwrapping of
      the DNA is not stably maintained in the nucleosome. H2A-H2B release and DNA
      unwrapping occur simultaneously, indicating that DNA is essential in stabilizing
      the dimer in the nucleosome. Our structures reveal intrinsic nucleosomal
      plasticity that is required for nucleosome stability and might be exploited by
      extrinsic protein factors.

PMID- 29323274
TI  - APOBEC3 induces mutations during repair of CRISPR-Cas9-generated DNA breaks.
AB  - The APOBEC-AID family of cytidine deaminase prefers single-stranded nucleic acids
      for cytidine-to-uridine deamination. Single-stranded nucleic acids are commonly
      involved in the DNA repair system for breaks generated by CRISPR-Cas9. Here, we
      show in human cells that APOBEC3 can trigger cytidine deamination of single
      stranded oligodeoxynucleotides, which ultimately results in base substitution
      mutations in genomic DNA through homology-directed repair (HDR) of Cas9-generated
      double-strand breaks. In addition, the APOBEC3-catalyzed deamination in genomic
      single-stranded DNA formed during the repair of Cas9 nickase-generated single
      strand breaks in human cells can be further processed to yield mutations mainly
      involving insertions or deletions (indels). Both APOBEC3-mediated deamination and
      DNA-repair proteins play important roles in the generation of these indels.
      Therefore, optimizing conditions for the repair of CRISPR-Cas9-generated DNA
      breaks, such as using double-stranded donors in HDR or temporarily suppressing
      endogenous APOBEC3s, can repress these unwanted mutations in genomic DNA.

PMID- 29323272
TI  - Dominant-negative SMARCA4 mutants alter the accessibility landscape of tissue
      unrestricted enhancers.
AB  - Mutation of SMARCA4 (BRG1), the ATPase of BAF (mSWI/SNF) and PBAF complexes,
      contributes to a range of malignancies and neurologic disorders. Unfortunately,
      the effects of SMARCA4 missense mutations have remained uncertain. Here we show
      that SMARCA4 cancer missense mutations target conserved ATPase surfaces and
      disrupt the mechanochemical cycle of remodeling. We find that heterozygous
      expression of mutants alters the open chromatin landscape at thousands of sites
      across the genome. Loss of DNA accessibility does not directly overlap with
      Polycomb accumulation, but is enriched in 'A compartments' at active enhancers,
      which lose H3K27ac but not H3K4me1. Affected positions include hundreds of sites
      identified as superenhancers in many tissues. Dominant-negative mutation induces
      pro-oncogenic expression changes, including increased expression of Myc and its
      target genes. Together, our data suggest that disruption of enhancer
      accessibility represents a key source of altered function in disorders with
      SMARCA4 mutations in a wide variety of tissues.

PMID- 29323276
TI  - Chd1 bends over backward to remodel.

PMID- 29323275
TI  - RNA-DamID reveals cell-type-specific binding of roX RNAs at chromatin-entry
      sites.
AB  - Thousands of long noncoding RNAs (lncRNAs) have been identified in eukaryotic
      genomes, many of which are expressed in spatially and temporally restricted
      patterns. Nonetheless, the roles of the majority of these transcripts are still
      unknown. One of the mechanisms by which lncRNAs function is through the
      modulation of chromatin states. To assess the functions of lncRNAs, we developed
      RNA-DamID, a novel approach that detects lncRNA-genome interactions in a cell
      type-specific manner in vivo with high sensitivity and accuracy. Identifying the
      cell-type-specific genome occupancy of lncRNAs is vital to understanding their
      mechanisms of action in development and disease. We used RNA-DamID to investigate
      targeting of the lncRNAs in the Drosophila dosage-compensation complex (DCC) and
      show that initial targeting is cell-type specific.

PMID- 29323277
TI  - Structure and dynamics of GPCR signaling complexes.
AB  - G-protein-coupled receptors (GPCRs) relay numerous extracellular signals by
      triggering intracellular signaling through coupling with G proteins and
      arrestins. Recent breakthroughs in the structural determination of GPCRs and GPCR
      transducer complexes represent important steps toward deciphering GPCR signal
      transduction at a molecular level. A full understanding of the molecular basis of
      GPCR-mediated signaling requires elucidation of the dynamics of receptors and
      their transducer complexes as well as their energy landscapes and conformational
      transition rates. Here, we summarize current insights into the structural
      plasticity of GPCR-G-protein and GPCR-arrestin complexes that underlies the
      regulation of the receptor's intracellular signaling profile.

PMID- 29323278
TI  - Structural biology of Zika virus and other flaviviruses.
AB  - Zika virus (ZIKV) is an enveloped, icosahedral flavivirus that has structural and
      functional similarities to other human flavivirus pathogens such as dengue
      (DENV), West Nile (WNV) and Japanese encephalitis (JEV) viruses. ZIKV infections
      have been linked to fetal microcephaly and the paralytic Guillain-Barre syndrome.
      This review provides a comparative structural analysis of the assembly,
      maturation and host-cell entry of ZIKV with other flaviviruses, especially DENV.
      We also discuss the mechanisms of neutralization by antibodies.

PMID- 29323280
TI  - Nucleotide exchange factors Fes1 and HspBP1 mimic substrate to release misfolded
      proteins from Hsp70.
AB  - Protein quality control depends on the tight regulation of interactions between
      molecular chaperones and polypeptide substrates. Substrate release from the
      chaperone Hsp70 is triggered by nucleotide-exchange factors (NEFs) that control
      folding and degradation fates via poorly understood mechanisms. We found that the
      armadillo-type NEFs budding yeast Fes1 and its human homolog HspBP1 employ
      flexible N-terminal release domains (RDs) with substrate-mimicking properties to
      ensure the efficient release of persistent substrates from Hsp70. The RD contacts
      the substrate-binding domain of the chaperone, competes with peptide substrate
      for binding and is essential for proper function in yeast and mammalian cells.
      Thus, the armadillo domain engages Hsp70 to trigger nucleotide exchange, whereas
      the RD safeguards the release of substrates. Our findings provide fundamental
      mechanistic insight into the functional specialization of Hsp70 NEFs and have
      implications for the understanding of proteostasis-related disorders, including
      Marinesco-Sjogren syndrome.

PMID- 29323279
TI  - Structural basis of TRPV5 channel inhibition by econazole revealed by cryo-EM.
AB  - The transient receptor potential vanilloid 5 (TRPV5) channel is a member of the
      transient receptor potential (TRP) channel family, which is highly selective for
      Ca2+, that is present primarily at the apical membrane of distal tubule
      epithelial cells in the kidney and plays a key role in Ca2+ reabsorption. Here we
      present the structure of the full-length rabbit TRPV5 channel as determined using
      cryo-EM in complex with its inhibitor econazole. This structure reveals that
      econazole resides in a hydrophobic pocket analogous to that occupied by
      phosphatidylinositides and vanilloids in TRPV1, thus suggesting conserved
      mechanisms for ligand recognition and lipid binding among TRPV channels. The
      econazole-bound TRPV5 structure adopts a closed conformation with a distinct
      lower gate that occludes Ca2+ permeation through the channel. Structural
      comparisons between TRPV5 and other TRPV channels, complemented with molecular
      dynamics (MD) simulations of the econazole-bound TRPV5 structure, allowed us to
      gain mechanistic insight into TRPV5 channel inhibition by small molecules.

PMID- 29323281
TI  - Bap (Sil1) regulates the molecular chaperone BiP by coupling release of
      nucleotide and substrate.
AB  - BiP is the endoplasmic member of the Hsp70 family. BiP is regulated by several co
      chaperones including the nucleotide-exchange factor (NEF) Bap (Sil1 in yeast).
      Bap is a two-domain protein. The interaction of the Bap C-terminal domain with
      the BiP ATPase domain is sufficient for its weak NEF activity. However,
      stimulation of the BiP ATPase activity requires full-length Bap, suggesting a
      complex interplay of these two factors. Here, single-molecule FRET experiments
      with mammalian proteins reveal that Bap affects the conformation of both BiP
      domains, including the lid subdomain, which is important for substrate binding.
      The largely unstructured Bap N-terminal domain promotes the substrate release
      from BiP. Thus, Bap is a conformational regulator affecting both nucleotide and
      substrate interactions. The preferential interaction with BiP in its ADP state
      places Bap at a late stage of the chaperone cycle, in which it coordinates
      release of substrate and ADP, thereby resetting BiP for ATP and substrate
      binding.

PMID- 29323283
TI  - NSMB at 25.

PMID- 29323282
TI  - MLL2 conveys transcription-independent H3K4 trimethylation in oocytes.
AB  - Histone 3 K4 trimethylation (depositing H3K4me3 marks) is typically associated
      with active promoters yet paradoxically occurs at untranscribed domains. Research
      to delineate the mechanisms of targeting H3K4 methyltransferases is ongoing. The
      oocyte provides an attractive system to investigate these mechanisms, because
      extensive H3K4me3 acquisition occurs in nondividing cells. We developed low-input
      chromatin immunoprecipitation to interrogate H3K4me3, H3K27ac and H3K27me3 marks
      throughout oogenesis. In nongrowing oocytes, H3K4me3 was restricted to active
      promoters, but as oogenesis progressed, H3K4me3 accumulated in a transcription
      independent manner and was targeted to intergenic regions, putative enhancers and
      silent H3K27me3-marked promoters. Ablation of the H3K4 methyltransferase gene
      Mll2 resulted in loss of transcription-independent H3K4 trimethylation but had
      limited effects on transcription-coupled H3K4 trimethylation or gene expression.
      Deletion of Dnmt3a and Dnmt3b showed that DNA methylation protects regions from
      acquiring H3K4me3. Our findings reveal two independent mechanisms of targeting
      H3K4me3 to genomic elements, with MLL2 recruited to unmethylated CpG-rich regions
      independently of transcription.

PMID- 29323284
TI  - Phases and rates of iron and magnetism changes during paddy soil development on
      calcareous marine sediment and acid Quaternary red-clay.
AB  - Dynamic changes in Fe oxides and magnetic properties during natural pedogenesis
      are well documented, but variations and controls of Fe and magnetism changes
      during anthropedogenesis of paddy soils strongly affected by human activities
      remain poorly understood. We investigated temporal changes in different Fe pools
      and magnetic parameters in soil profiles from two contrasting paddy soil
      chronosequences developed on calcareous marine sediment and acid Quaternary red
      clay in Southern China to understand the directions, phases and rates of Fe and
      magnetism evolution in Anthrosols. Results showed that paddy soil evolution under
      the influence of artificial submergence and drainage caused changes in soil
      moisture regimes and redox conditions with both time and depth that controlled Fe
      transport and redistribution, leading to increasing profile differentiation of Fe
      oxides, rapid decrease of magnetic parameters, and formation of diagnostic
      horizons and features, irrespective of the different parent materials. However,
      the initial parent material characteristics (pH, Fe content and composition,
      weathering degree and landscape positions) exerted a strong influence on the
      rates and trajectories of Fe oxides evolution as well as the phases and rates of
      magnetism changes. This influence diminished with time as prolonged rice
      cultivation drove paddy soil evolving to common pedogenic features.

PMID- 29323285
TI  - A set of synthetic versatile genetic control elements for the efficient
      expression of genes in Actinobacteria.
AB  - The design and engineering of secondary metabolite gene clusters that are
      characterized by complicated genetic organization, require the development of
      collections of well-characterized genetic control elements that can be reused
      reliably. Although a few intrinsic terminators and RBSs are used routinely, their
      translation and termination efficiencies have not been systematically studied in
      Actinobacteria. Here, we analyzed the influence of the regions surrounding RBSs
      on gene expression in these bacteria. We demonstrated that inappropriate RBSs can
      reduce the expression efficiency of a gene to zero. We developed a genetic device
      - an in vivo RBS-selector - that allows selection of an optimal RBS for any gene
      of interest, enabling rational control of the protein expression level. In
      addition, a genetic tool that provides the opportunity for measurement of
      termination efficiency was developed. Using this tool, we found strong
      terminators that lead to a 17-100-fold reduction in downstream expression and are
      characterized by sufficient sequence diversity to reduce homologous recombination
      when used with other elements. For the first time, a C-terminal degradation tag
      was employed for the control of protein stability in Streptomyces. Finally, we
      describe a collection of regulatory elements that can be used to control
      metabolic pathways in Actinobacteria.

PMID- 29323286
TI  - Conditional punishment is a double-edged sword in promoting cooperation.
AB  - Punishment is widely recognized as an effective approach for averting from
      exploitation by free-riders in human society. However, punishment is costly, and
      thus rational individuals are unwilling to take the punishing action, resulting
      in the second-order free-rider problem. Recent experimental study evidences that
      individuals prefer conditional punishment, and their punishing decision depends
      on other members' punishing decisions. In this work, we thus propose a
      theoretical model for conditional punishment and investigate how such conditional
      punishment influences cooperation in the public goods game. Considering
      conditional punishers only take the punishing action when the number of
      unconditional punishers exceeds a threshold number, we demonstrate that such
      conditional punishment induces the effect of a double-edged sword on the
      evolution of cooperation both in well-mixed and structured populations.
      Specifically, when it is relatively easy for conditional punishers to engage in
      the punishment activity corresponding to a low threshold value, cooperation can
      be promoted in comparison with the case without conditional punishment. Whereas
      when it is relatively difficult for conditional punishers to engage in the
      punishment activity corresponding to a high threshold value, cooperation is
      inhibited in comparison with the case without conditional punishment. Moreover,
      we verify that such double-edged sword effect exists in a wide range of model
      parameters and can be still observed in other different punishment regimes.

PMID- 29323288
TI  - Impacts of simulated erosion and soil amendments on greenhouse gas fluxes and
      maize yield in Miamian soil of central Ohio.
AB  - Erosion-induced topsoil loss is a threat to sustainable productivity. Topsoil
      removal from, or added to, the existing surface is an efficient technique to
      simulate on-site soil erosion and deposition. A 15-year simulated erosion was
      conducted at Waterman Farm of Ohio State University to assess impacts of topsoil
      depth on greenhouse gas (GHG) emissions and maize yield. Three topsoil treatments
      were investigated: 20 cm topsoil removal, 20 cm topsoil addition, and undisturbed
      control. Results show that the average global warming potential (GWP) (Mg CO2 Eq
      ha-1 growing season-1) from the topsoil removal plot (18.07) exhibited roughly
      the same value as that from the undisturbed control plot (18.11), but declined
      evidently from the topsoil addition plot (10.58). Maize yield decreased by 51% at
      the topsoil removal plot, while increased by 47% at the topsoil addition plot,
      when compared with the undisturbed control (7.45 Mg ha-1). The average GWP of
      erosion-deposition process was 21% lower than that of the undisturbed control,
      but that greenhouse gas intensity (GHGI) was 22% higher due to lower yields from
      the topsoil removal plot. Organic manure application enhanced GWP by 15%, and
      promoted maize yield by 18%, but brought a small reduction GHGI (3%) against the
      N-fertilizer application.

PMID- 29323287
TI  - Disposition of a Glucose Load into Hepatic Glycogen by Direct and Indirect
      Pathways in Juvenile Seabass and Seabream.
AB  - In carnivorous fish, conversion of a glucose load to hepatic glycogen is widely
      used to assess their metabolic flexibility towards carbohydrate utilization, but
      the activities of direct and indirect pathways in this setting are unclear. We
      assessed the conversion of an intraperitoneal glucose load (2 g.kg-1) enriched
      with [U-13C6]glucose to hepatic glycogen in juvenile seabass and seabream. 13C
      NMR analysis of glycogen was used to determine the contribution of the load to
      glycogen synthesis via direct and indirect pathways at 48-hr post-injection. For
      seabass, [U-13C6]glucose was accompanied by deuterated water and 2H-NMR analysis
      of glycogen 2H-enrichment, allowing endogenous substrate contributions to be
      assessed as well. For fasted seabass and seabream, 47 +/- 5% and 64 +/- 10% of
      glycogen was synthesized from the load, respectively. Direct and indirect
      pathways contributed equally (25 +/- 3% direct, 21 +/- 1% indirect for seabass;
      35 +/- 7% direct, 29 +/- 4% indirect for seabream). In fasted seabass,
      integration of 2H- and 13C-NMR analysis indicated that endogenous glycerol and
      anaplerotic substrates contributed an additional 7 +/- 2% and 7 +/- 1%,
      respectively. In fed seabass, glucose load contributions were residual and
      endogenous contributions were negligible. Concluding, direct and indirect
      pathways contributed equally and substantially to fasting hepatic glycogen
      repletion from a glucose load in juvenile seabream and seabass.

PMID- 29323289
TI  - Hypertension: New US blood-pressure guidelines - who asked the patients?

PMID- 29323290
TI  - Clonal analysis of lineage fate in native haematopoiesis.
AB  - Haematopoiesis, the process of mature blood and immune cell production, is
      functionally organized as a hierarchy, with self-renewing haematopoietic stem
      cells and multipotent progenitor cells sitting at the very top. Multiple models
      have been proposed as to what the earliest lineage choices are in these primitive
      haematopoietic compartments, the cellular intermediates, and the resulting
      lineage trees that emerge from them. Given that the bulk of studies addressing
      lineage outcomes have been performed in the context of haematopoietic
      transplantation, current models of lineage branching are more likely to represent
      roadmaps of lineage potential than native fate. Here we use transposon tagging to
      clonally trace the fates of progenitors and stem cells in unperturbed
      haematopoiesis. Our results describe a distinct clonal roadmap in which the
      megakaryocyte lineage arises largely independently of other haematopoietic fates.
      Our data, combined with single-cell RNA sequencing, identify a functional
      hierarchy of unilineage- and oligolineage-producing clones within the multipotent
      progenitor population. Finally, our results demonstrate that traditionally
      defined long-term haematopoietic stem cells are a significant source of
      megakaryocyte-restricted progenitors, suggesting that the megakaryocyte lineage
      is the predominant native fate of long-term haematopoietic stem cells. Our study
      provides evidence for a substantially revised roadmap for unperturbed
      haematopoiesis, and highlights unique properties of multipotent progenitors and
      haematopoietic stem cells in situ.

PMID- 29323291
TI  - Neurexin controls plasticity of a mature, sexually dimorphic neuron.
AB  - During development and adulthood, brain plasticity is evident at several levels,
      from synaptic structure and function to the outgrowth of dendrites and axons.
      Whether and how sex impinges on neuronal plasticity is poorly understood. Here we
      show that the sex-shared GABA (gamma-aminobutyric acid)-releasing DVB neuron in
      Caenorhabditis elegans displays experience-dependent and sexually dimorphic
      morphological plasticity, characterized by the stochastic and dynamic addition of
      multiple neurites in adult males. These added neurites enable synaptic rewiring
      of the DVB neuron and instruct a functional switch of the neuron that directly
      modifies a step of male mating behaviour. Both DVB neuron function and male
      mating behaviour can be altered by experience and by manipulation of postsynaptic
      activity. The outgrowth of DVB neurites is promoted by presynaptic neurexin and
      antagonized by postsynaptic neuroligin, revealing a non-conventional activity and
      mode of interaction of these conserved, human-disease-relevant factors.

PMID- 29323292
TI  - Bright triplet excitons in caesium lead halide perovskites.
AB  - Nanostructured semiconductors emit light from electronic states known as
      excitons. For organic materials, Hund's rules state that the lowest-energy
      exciton is a poorly emitting triplet state. For inorganic semiconductors, similar
      rules predict an analogue of this triplet state known as the 'dark exciton'.
      Because dark excitons release photons slowly, hindering emission from inorganic
      nanostructures, materials that disobey these rules have been sought. However,
      despite considerable experimental and theoretical efforts, no inorganic
      semiconductors have been identified in which the lowest exciton is bright. Here
      we show that the lowest exciton in caesium lead halide perovskites (CsPbX3, with
      X = Cl, Br or I) involves a highly emissive triplet state. We first use an
      effective-mass model and group theory to demonstrate the possibility of such a
      state existing, which can occur when the strong spin-orbit coupling in the
      conduction band of a perovskite is combined with the Rashba effect. We then apply
      our model to CsPbX3 nanocrystals, and measure size- and composition-dependent
      fluorescence at the single-nanocrystal level. The bright triplet character of the
      lowest exciton explains the anomalous photon-emission rates of these materials,
      which emit about 20 and 1,000 times faster than any other semiconductor
      nanocrystal at room and cryogenic temperatures, respectively. The existence of
      this bright triplet exciton is further confirmed by analysis of the fine
      structure in low-temperature fluorescence spectra. For semiconductor
      nanocrystals, which are already used in lighting, lasers and displays, these
      excitons could lead to materials with brighter emission. More generally, our
      results provide criteria for identifying other semiconductors that exhibit bright
      excitons, with potential implications for optoelectronic devices.

PMID- 29323293
TI  - Precision editing of the gut microbiota ameliorates colitis.
AB  - Inflammatory diseases of the gastrointestinal tract are frequently associated
      with dysbiosis, characterized by changes in gut microbial communities that
      include an expansion of facultative anaerobic bacteria of the Enterobacteriaceae
      family (phylum Proteobacteria). Here we show that a dysbiotic expansion of
      Enterobacteriaceae during gut inflammation could be prevented by tungstate
      treatment, which selectively inhibited molybdenum-cofactor-dependent microbial
      respiratory pathways that are operational only during episodes of inflammation.
      By contrast, we found that tungstate treatment caused minimal changes in the
      microbiota composition under homeostatic conditions. Notably, tungstate-mediated
      microbiota editing reduced the severity of intestinal inflammation in mouse
      models of colitis. We conclude that precision editing of the microbiota
      composition by tungstate treatment ameliorates the adverse effects of dysbiosis
      in the inflamed gut.

PMID- 29323294
TI  - Terminal Pleistocene Alaskan genome reveals first founding population of Native
      Americans.
AB  - Despite broad agreement that the Americas were initially populated via Beringia,
      the land bridge that connected far northeast Asia with northwestern North America
      during the Pleistocene epoch, when and how the peopling of the Americas occurred
      remains unresolved. Analyses of human remains from Late Pleistocene Alaska are
      important to resolving the timing and dispersal of these populations. The remains
      of two infants were recovered at Upward Sun River (USR), and have been dated to
      around 11.5 thousand years ago (ka). Here, by sequencing the USR1 genome to an
      average coverage of approximately 17 times, we show that USR1 is most closely
      related to Native Americans, but falls basal to all previously sequenced
      contemporary and ancient Native Americans. As such, USR1 represents a distinct
      Ancient Beringian population. Using demographic modelling, we infer that the
      Ancient Beringian population and ancestors of other Native Americans descended
      from a single founding population that initially split from East Asians around 36
      +/- 1.5 ka, with gene flow persisting until around 25 +/- 1.1 ka. Gene flow from
      ancient north Eurasians into all Native Americans took place 25-20 ka, with
      Ancient Beringians branching off around 22-18.1 ka. Our findings support a long
      term genetic structure in ancestral Native Americans, consistent with the
      Beringian 'standstill model'. We show that the basal northern and southern Native
      American branches, to which all other Native Americans belong, diverged around
      17.5-14.6 ka, and that this probably occurred south of the North American ice
      sheets. We also show that after 11.5 ka, some of the northern Native American
      populations received gene flow from a Siberian population most closely related to
      Koryaks, but not Palaeo-Eskimos, Inuits or Kets, and that Native American gene
      flow into Inuits was through northern and not southern Native American groups.
      Our findings further suggest that the far-northern North American presence of
      northern Native Americans is from a back migration that replaced or absorbed the
      initial founding population of Ancient Beringians.

PMID- 29323296
TI  - A rapid decrease in the rotation rate of comet 41P/Tuttle-Giacobini-Kresak.
AB  - Cometary outgassing can produce torques that change the spin state of the
      cometary nucleus, which in turn influences the evolution and lifetime of the
      comet. If these torques increase the rate of rotation to the extent that
      centripetal forces exceed the material strength of the nucleus, the comet can
      fragment. Torques that slow down the rotation can cause the spin state to become
      unstable, but if the torques persist the nucleus can eventually reorient itself
      and the rotation rate can increase again. Simulations predict that most comets go
      through a short phase of rapid changes in spin state, after which changes occur
      gradually over longer times. Here we report observations of comet 41P/Tuttle
      Giacobini-Kresak during its close approach to Earth (0.142 astronomical units,
      approximately 21 million kilometres, on 1 April 2017) that reveal a rapid
      decrease in rotation rate. Between March and May 2017, the apparent rotation
      period of the nucleus increased from 20 hours to more than 46 hours-a rate of
      change of more than an order of magnitude larger than has hitherto been measured.
      This phenomenon must have been caused by the gas emission from the comet aligning
      in such a way that it produced an anomalously strong torque that slowed the spin
      rate of the nucleus. The behaviour of comet 41P/Tuttle-Giacobini-Kresak suggests
      that it is in a distinct evolutionary state and that its rotation may be
      approaching the point of instability.

PMID- 29323295
TI  - Alcohol and endogenous aldehydes damage chromosomes and mutate stem cells.
AB  - Haematopoietic stem cells renew blood. Accumulation of DNA damage in these cells
      promotes their decline, while misrepair of this damage initiates malignancies.
      Here we describe the features and mutational landscape of DNA damage caused by
      acetaldehyde, an endogenous and alcohol-derived metabolite. This damage results
      in DNA double-stranded breaks that, despite stimulating recombination repair,
      also cause chromosome rearrangements. We combined transplantation of single
      haematopoietic stem cells with whole-genome sequencing to show that this damage
      occurs in stem cells, leading to deletions and rearrangements that are indicative
      of microhomology-mediated end-joining repair. Moreover, deletion of p53
      completely rescues the survival of aldehyde-stressed and mutated haematopoietic
      stem cells, but does not change the pattern or the intensity of genome
      instability within individual stem cells. These findings characterize the
      mutation of the stem-cell genome by an alcohol-derived and endogenous source of
      DNA damage. Furthermore, we identify how the choice of DNA-repair pathway and a
      stringent p53 response limit the transmission of aldehyde-induced mutations in
      stem cells.

PMID- 29323297
TI  - An extreme magneto-ionic environment associated with the fast radio burst source
      FRB 121102.
AB  - Fast radio bursts are millisecond-duration, extragalactic radio flashes of
      unknown physical origin. The only known repeating fast radio burst source-FRB
      121102-has been localized to a star-forming region in a dwarf galaxy at redshift
      0.193 and is spatially coincident with a compact, persistent radio source. The
      origin of the bursts, the nature of the persistent source and the properties of
      the local environment are still unclear. Here we report observations of FRB
      121102 that show almost 100 per cent linearly polarized emission at a very high
      and variable Faraday rotation measure in the source frame (varying from +1.46 *
      105 radians per square metre to +1.33 * 105 radians per square metre at epochs
      separated by seven months) and narrow (below 30 microseconds) temporal structure.
      The large and variable rotation measure demonstrates that FRB 121102 is in an
      extreme and dynamic magneto-ionic environment, and the short durations of the
      bursts suggest a neutron star origin. Such large rotation measures have hitherto
      been observed only in the vicinities of massive black holes (larger than about
      10,000 solar masses). Indeed, the properties of the persistent radio source are
      compatible with those of a low-luminosity, accreting massive black hole. The
      bursts may therefore come from a neutron star in such an environment or could be
      explained by other models, such as a highly magnetized wind nebula or supernova
      remnant surrounding a young neutron star.

PMID- 29323300
TI  - Chemists go green to make better blue jeans.

PMID- 29323299
TI  - Rotation in [C ii]-emitting gas in two galaxies at a redshift of 6.8.
AB  - The earliest galaxies are thought to have emerged during the first billion years
      of cosmic history, initiating the ionization of the neutral hydrogen that
      pervaded the Universe at this time. Studying this 'epoch of reionization'
      involves looking for the spectral signatures of ancient galaxies that are, owing
      to the expansion of the Universe, now very distant from Earth and therefore
      exhibit large redshifts. However, finding these spectral fingerprints is
      challenging. One spectral characteristic of ancient and distant galaxies is
      strong hydrogen-emission lines (known as Lyman-alpha lines), but the neutral
      intergalactic medium that was present early in the epoch of reionization scatters
      such Lyman-alpha photons. Another potential spectral identifier is the line at
      wavelength 157.4 micrometres of the singly ionized state of carbon (the [C ii]
      lambda = 157.74 MUm line), which signifies cooling gas and is expected to have
      been bright in the early Universe. However, so far Lyman-alpha-emitting galaxies
      from the epoch of reionization have demonstrated much fainter [C ii] luminosities
      than would be expected from local scaling relations, and searches for the [C ii]
      line in sources without Lyman-alpha emission but with photometric redshifts
      greater than 6 (corresponding to the first billion years of the Universe) have
      been unsuccessful. Here we identify [C ii] lambda = 157.74 MUm emission from two
      sources that we selected as high-redshift candidates on the basis of near
      infrared photometry; we confirm that these sources are two galaxies at redshifts
      of z = 6.8540 +/- 0.0003 and z = 6.8076 +/- 0.0002. Notably, the luminosity of
      the [C ii] line from these galaxies is higher than that found previously in star
      forming galaxies with redshifts greater than 6.5. The luminous and extended [C
      ii] lines reveal clear velocity gradients that, if interpreted as rotation, would
      indicate that these galaxies have similar dynamic properties to the turbulent yet
      rotation-dominated disks that have been observed in Halpha-emitting galaxies two
      billion years later, at 'cosmic noon'.

PMID- 29323302
TI  - Typhoid vaccine, dementia research and discrimination in science.

PMID- 29323301
TI  - Scientific ballooning takes off.

PMID- 29323298
TI  - A metabolic function of FGFR3-TACC3 gene fusions in cancer.
AB  - Chromosomal translocations that generate in-frame oncogenic gene fusions are
      notable examples of the success of targeted cancer therapies. We have previously
      described gene fusions of FGFR3-TACC3 (F3-T3) in 3% of human glioblastoma cases.
      Subsequent studies have reported similar frequencies of F3-T3 in many other
      cancers, indicating that F3-T3 is a commonly occuring fusion across all tumour
      types. F3-T3 fusions are potent oncogenes that confer sensitivity to FGFR
      inhibitors, but the downstream oncogenic signalling pathways remain unknown. Here
      we show that human tumours with F3-T3 fusions cluster within transcriptional
      subgroups that are characterized by the activation of mitochondrial functions. F3
      T3 activates oxidative phosphorylation and mitochondrial biogenesis and induces
      sensitivity to inhibitors of oxidative metabolism. Phosphorylation of the
      phosphopeptide PIN4 is an intermediate step in the signalling pathway of the
      activation of mitochondrial metabolism. The F3-T3-PIN4 axis triggers the
      biogenesis of peroxisomes and the synthesis of new proteins. The anabolic
      response converges on the PGC1alpha coactivator through the production of
      intracellular reactive oxygen species, which enables mitochondrial respiration
      and tumour growth. These data illustrate the oncogenic circuit engaged by F3-T3
      and show that F3-T3-positive tumours rely on mitochondrial respiration,
      highlighting this pathway as a therapeutic opportunity for the treatment of
      tumours with F3-T3 fusions. We also provide insights into the genetic alterations
      that initiate the chain of metabolic responses that drive mitochondrial
      metabolism in cancer.

PMID- 29323303
TI  - How to see a memory.

PMID- 29323306
TI  - Combinations on trial.

PMID- 29323304
TI  - Tooth scratches reveal new clues to pterosaur diets.

PMID- 29323307
TI  - Images of the year.

PMID- 29323308
TI  - Climate scientists unlock secrets of 'blue carbon'.

PMID- 29323309
TI  - Gene-drive e-mails were legally requested.

PMID- 29323311
TI  - Germany vs Elsevier: universities win temporary journal access after refusing to
      pay fees.

PMID- 29323312
TI  - Test climate targets using fragile ecosystems.

PMID- 29323313
TI  - Mystery funders of Arecibo radio telescope can celebrate an early success.

PMID- 29323314
TI  - Gender pay gap persists.

PMID- 29323315
TI  - Tumour lymph vessels boost immunotherapy.

PMID- 29323316
TI  - A quality-control test for predatory journals.

PMID- 29323317
TI  - Funders should mandate open citations.

PMID- 29323318
TI  - Protect the high seas from harm.

PMID- 29323319
TI  - Silicon gains ground in quantum-computing race.

PMID- 29323320
TI  - Telling details of breast-cancer recurrence.

PMID- 29323321
TI  - When sickness interrupts science.

PMID- 29323322
TI  - Neuronal plasticity in nematode worms.

PMID- 29323323
TI  - Rule-breaking perovskites.

PMID- 29323325
TI  - An ode to gene edits that prevent deafness.

PMID- 29323326
TI  - Male scientists given more opportunities to address colloquia.

PMID- 29323327
TI  - Indonesian scientists embrace preprint server.

PMID- 29323328
TI  - Exoplanet science 2.0.

PMID- 29323329
TI  - Cometary spin-down.

PMID- 29323331
TI  - Dogma-breaking catalysis.

PMID- 29323330
TI  - Step aside CERN: There's a cheaper way to break open physics.

PMID- 29323333
TI  - Controlling lightwave in Riemann space by merging geometrical optics with
      transformation optics.
AB  - In geometrical optical design, we only need to choose a suitable combination of
      lenses, prims, and mirrors to design an optical path. It is a simple and classic
      method for engineers. However, people cannot design fantastical optical devices
      such as invisibility cloaks, optical wormholes, etc. by geometrical optics.
      Transformation optics has paved the way for these complicated designs. However,
      controlling the propagation of light by transformation optics is not a direct
      design process like geometrical optics. In this study, a novel mixed method for
      optical design is proposed which has both the simplicity of classic geometrical
      optics and the flexibility of transformation optics. This mixed method overcomes
      the limitations of classic optical design; at the same time, it gives intuitive
      guidance for optical design by transformation optics. Three novel optical devices
      with fantastic functions have been designed using this mixed method, including
      asymmetrical transmissions, bidirectional focusing, and bidirectional cloaking.
      These optical devices cannot be implemented by classic optics alone and are also
      too complicated to be designed by pure transformation optics. Numerical
      simulations based on both the ray tracing method and full-wave simulation method
      are carried out to verify the performance of these three optical devices.

PMID- 29323334
TI  - Unveiling the piezoelectric nature of polar alpha-phase P(VDF-TrFE) at quasi-two
      dimensional limit.
AB  - Piezoelectric response of P(VDF-TrFE), which is modulated by the dipole density
      due to the polarization switching on applying an electric field, allows it act as
      the fundamental components for electromechanical systems. As proposed since the
      1970s, its polar alpha-phase is supposed to yield an enhanced piezoelectric
      activity. However, its experimental verification has never been reported,
      hampered by a substantial challenge for the achievement of a smooth, neat alpha
      phase film. Here, we prepare ultrathin crystalline alpha-phase P(VDF-TrFE) films
      on the AlOx/Al-coated SiO2/Si substrates via a solution-based approach at room
      temperature. Thus, we unveil the piezoelectric nature of the polar alpha-phase
      P(VDF-TrFE) at a quasi-two-dimensional limit. The obtained values of the relative
      morphological deformation, the local effective piezoelectric coefficient, and the
      electric field-induced strain reach up to 37 pm, -46.4 pm V-1, and 4.1%,
      respectively. Such a robust piezoelectric response is even higher than that of
      the beta-phase. Besides, the evolution of piezoelectricity, which is related to
      the piezoelectric properties of two polarization states, is also studied. Our
      work can enable the exploration of the prospective applications of polar alpha
      phase P(VDF-TrFE) films.

PMID- 29323337
TI  - Regulatory T cells as a new therapeutic target for atherosclerosis.
AB  - Atherosclerosis is an autoimmune disease caused by self- and non-self-antigens
      contributing to excessive activation of T and B cell immune responses. These
      responses further aggravate vascular infiammation and promote progression of
      atherosclerosis and vulnerability to plaques via releasing pro-infiammatory
      cytokines. Regulatory T cells (Tregs) as the major immunoregulatory cells, in
      particular, induce and maintain immune homeostasis and tolerance by suppressing
      the immune responses of various cells such as T and B cells, natural killer (NK)
      cells, monocytes, and dendritic cells (DCs), as well as by secreting inhibitory
      cytokines interleukin (IL)-10, IL-35 and transcription growth factor beta (TGF
      beta) in both physiological and pathological states. Numerous evidence
      demonstrates that reduced numbers and dysfunction of Treg may be involveved in
      atherosclerosis pathogenesis. Increasing or restoring the numbers and improving
      the immunosuppressive capacity of Tregs may serve as a fundamental immunotherapy
      to treat atherosclerotic cardiovascular diseases. In this article, we briefiy
      present current knowledge of Treg subsets, summarize the relationship between
      Tregs and atherosclerosis development, and discuss the possibilities of
      regulating Tregs for prevention of atherosclerosis pathogenesis and enhancement
      of plaque stability. Although the exact molecular mechanisms of Treg-mediated
      protection against atherosclerosis remain to be elucidated, the strategies for
      targeting the regulation of Tregs may provide specific and significant approaches
      for the prevention and treatment of atherosclerotic cardiovascular diseases.

PMID- 29323335
TI  - Tanshinol alleviates impaired bone formation by inhibiting adipogenesis via
      KLF15/PPARgamma2 signaling in GIO rats.
AB  - Glucocorticoid (GC)-induced osteoporosis (GIO) is characterized by impaired bone
      formation, which can be alleviated by tanshinol, an aqueous polyphenol isolated
      from Salvia miltiorrhiza Bunge. In this study we investigated the molecular
      mechanisms underlying GC-induced modulation of osteogenesis as well as the
      possibility of using tanshinol to interfere with GIO. Female SD rats aged 4
      months were orally administered distilled water (Con), prednisone (GC, 5 mg.kg
      1.d-1), GC plus tanshinol (Tan, 16 mg.kg-1.d-1) or GC plus resveratrol (Res, 5
      mg.kg-1.d-1) for 14 weeks. After the rats were sacrificed, samples of bone
      tissues were collected. The changes in bone formation were assessed using Micro
      CT, histomorphometry, and biomechanical assays. Expression of Kruppel-like factor
      15 (KLF15), peroxisome proliferator-activated receptor gamma 2 (PPARgamma 2) and
      other signaling proteins in skeletal tissue was measured with Western blotting
      and quantitative RT-PCR. GC treatment markedly increased the expression of KLF15,
      PPARgamma2, C/EBPalpha and aP2, which were related to adipogenesis, upregulated
      FoxO3a pathway proteins (FoxO3a and Gadd45a), and suppressed the canonical Wnt
      signaling (beta-catenin and Axin2), which was required for osteogenesis. Thus, GC
      significantly decreased bone mass and bone quality. Co-treatment with Tan or Res
      effectively counteracted GC-impaired bone formation, suppressed GC-induced
      adipogenesis, and restored abnormal expression of the signaling molecules in GIO
      rats. We conclude that tanshinol counteracts GC-decreased bone formation by
      inhibiting marrow adiposity via the KLF15/PPARgamma2/FoxO3a/Wnt pathway.

PMID- 29323336
TI  - Schisandrin ameliorates cognitive impairment and attenuates Abeta deposition in
      APP/PS1 transgenic mice: involvement of adjusting neurotransmitters and their
      metabolite changes in the brain.
AB  - Neurotransmitters (NTs) in the brain are involved in neurodegenerative diseases,
      such as Alzheimer's disease (AD). Schisandrin is a major ingredient of Schisandra
      chinensis (Turcz.) Baill and has been used for the treatment of AD. In this study
      we examined the therapeutic effects of schisandrin in APP/PS1 transgenic mice,
      and correlated the beneficial effects on cognitive impairment with the
      adjustments in NTs and their metabolites in the mouse brains. APP/PS1 mice were
      treated with schisandrin (2 mg.kg-1.d-1, ip) for 2 weeks. In Morris Water Maze
      test; untreated APP/PS1 mice displayed significant cognitive impairment compared
      with normal mice; schisandrin administration ameliorated the cognitive impairment
      and significantly decreased Abeta deposition in the hippocampus. In order to
      assess the effects of schisandrin on NTs and their metabolites, we developed a
      rapid and sensitive UPLC-MS/MS method for simultaneous determination of
      serotonin, 5-hydroxyindole acetic acid, dopamine, norepinephrine, gamma
      aminobutyric acid, glutamic acid, homovanillic acid, 3,4-dihydroxyphenylacetic
      acid and acetylcholine in mouse brains. This method conformed to methodology
      validation requirements. We found that there were statistically significant
      differences in these NTs and their metabolites between untreated APP/PS1 mice and
      normal mice, whereas schisandrin administration restored the abnormal NTs and
      their metabolites levels. These results suggest that schisandrin could alter the
      levels of these NTs and their metabolites in the brain, thus ameliorating
      learning and memory impairments in APP/PS1 mice.

PMID- 29323338
TI  - Ulinastatin attenuates LPS-induced inflammation in mouse macrophage RAW264.7
      cells by inhibiting the JNK/NF-kappaB signaling pathway and activating the
      PI3K/Akt/Nrf2 pathway.
AB  - Ulinastatin (UTI) is a broad-spectrum serine protease inhibitor isolated and
      purified from human urine with strong anti-inflammatory and cytoprotective
      actions, which is widely used for the treatment of various diseases, such as
      pancreatitis and sepsis. Although the therapeutic effects of UTI are reported to
      be associated with a variety of mechanisms, the signaling pathways mediating the
      anti-inflammatory action of UTI remain to be elucidated. In the present study we
      carried out a systematic study on the anti-inflammatory and anti-oxidative
      mechanisms of UTI and their relationships in LPS-treated RAW264.7 cells.
      Pretreatment with UTI (1000 and 5000 U/mL) dose-dependently decreased the mRNA
      levels of pro-inflammatory cytokines (IL-1beta, IL-6, TNF-alpha, iNOS) and
      upregulated anti-inflammatory cytokines (IL-10 and TGF-beta1) in LPS-treated
      RAW264.7 cells. UTI pretreatment significantly inhibited the nuclear
      translocation of NF-kappaB by preventing the degradation of IkappaB-alpha. UTI
      pretreatment only markedly inhibited the phosphorylation of JNK at Thr183, but it
      did not affect the phosphorylation of JNK at Tyr185, ERK-1/2 and p38 MAPK; JNK
      was found to function upstream of the IkappaB-alpha/NF-kappaB signaling pathway.
      Furthermore, UTI pretreatment significantly suppressed LPS-induced ROS production
      by activating PI3K/Akt pathways and the nuclear translocation of Nrf2 via
      promotion of p62-associated Keap1 degradation. However, JNK was not involved in
      mediating the anti-oxidative stress effects of UTI. In summary, this study shows
      that UTI exerts both anti-inflammatory and anti-oxidative effects by targeting
      the JNK/NF-kappaB and PI3K/Akt/Nrf2 pathways.

PMID- 29323339
TI  - A green method to leach vanadium and chromium from residue using NaOH-H2O2.
AB  - Hydrogen peroxide as an oxidant was applied in leaching of vanadium and chromium
      in concentrated NaOH solution. Under the optimal reaction conditions (the liquid
      to solid ratio of 4.0 ml/g, residue particle size of <200 mesh, the mass ratio of
      NaOH-to-residue of 1.0 g/g, the volume ratio of H2O2-to-residue of 1.2 ml/g,
      reaction temperature of 90  degrees C and reaction time of 120 min), the leaching
      efficiency of vanadium and chromium could reach up to 98.60% and 86.49%,
      respectively. Compared with the current liquid-phase oxidation technologies, the
      reaction temperature was 90-310  degrees C lower, and the NaOH concentration of
      the reaction medium is lower by more than 50 wt% (the mass ratio of NaOH-to
      residue of 1.0 g/g equals to concentration of 20 wt%). The kinetics study
      revealed that leaching process of chromium and vanadium were interpreted with
      shrinking core model under chemical reaction control. The apparent activation
      energy of chromium and vanadium dissolution was 22.19 kJ/mol and 6.95 kJ/mol,
      respectively.

PMID- 29323340
TI  - Osteoarthritis in 2017: Latest advances in the management of knee OA.

PMID- 29323341
TI  - Rheumatoid arthritis in 2017: Protective dietary and hormonal factors brought to
      light.

PMID- 29323342
TI  - Paediatric rheumatology in 2017: Child-centred research is the key to progress.

PMID- 29323345
TI  - Osteoporosis in 2017: Addressing the crisis in the treatment of osteoporosis.

PMID- 29323346
TI  - Inflammation in 2017: Connectivity to other fields brings new ideas.

PMID- 29323347
TI  - Rheumatoid arthritis: IFNgamma drives synovial tissue remodelling.

PMID- 29323343
TI  - Targeting lymphatic function as a novel therapeutic intervention for rheumatoid
      arthritis.
AB  - Although clinical outcomes for patients with rheumatoid arthritis (RA) have
      greatly improved with the use of biologic and conventional DMARDs, approximately
      40% of patients do not achieve primary clinical outcomes in randomized trials,
      and only a small proportion achieve lasting remission. Over the past decade,
      studies in murine models point to the critical role of the lymphatic system in
      the pathogenesis and therapy of inflammatory-erosive arthritis, presumably by the
      removal of catabolic factors, cytokines and inflammatory cells from the inflamed
      synovium. Murine studies demonstrate that lymphatic drainage increases at the
      onset of inflammatory-erosive arthritis but, as inflammation progresses to a more
      chronic phase, lymphatic clearance declines and both structural and cellular
      changes are observed in the draining lymph node. Specifically, chronic damage to
      the lymphatic vessel from persistent inflammation results in loss of lymphatic
      vessel contraction followed by lymph node collapse, reduced lymphatic drainage,
      and ultimately severe synovitis and joint erosion. Notably, clinical pilot
      studies in patients with RA report lymph node changes following treatment, and
      thus draining lymphatic vessels and nodes could represent a potential biomarker
      of arthritis activity and response to therapy. Most importantly, targeting
      lymphatics represents an innovative strategy for therapeutic intervention for RA.

PMID- 29323344
TI  - Updating osteoimmunology: regulation of bone cells by innate and adaptive
      immunity.
AB  - Osteoimmunology encompasses all aspects of the cross-regulation of bone and the
      immune system, including various cell types, signalling pathways, cytokines and
      chemokines, under both homeostatic and pathogenic conditions. A number of key
      areas are of increasing interest and relevance to osteoimmunology researchers.
      Although rheumatoid arthritis has long been recognized as one of the most common
      autoimmune diseases to affect bone integrity, researchers have focused increased
      attention on understanding how molecular triggers and innate signalling pathways
      (such as Toll-like receptors and purinergic signalling pathways) related to
      pathogenic and/or commensal microbiota are relevant to bone biology and rheumatic
      diseases. Additionally, although most discussions relating to osteoimmune
      regulation of homeostasis and disease have focused on the effects of adaptive
      immune responses on bone, evidence exists of the regulation of immune cells by
      bone cells, a concept that is consistent with the established role of the bone
      marrow in the development and homeostasis of the immune system. The active
      regulation of immune cells by bone cells is an interesting emerging component of
      investigations that seek to understand how to control immune-associated diseases
      of the bone and joints.

PMID- 29323349
TI  - Establishing stability: exploring the meaning of 'home' for women who have
      experienced intimate partner violence.
AB  - There is evidence that involuntary housing instability may undermine health and
      well-being. For women who have experienced intimate partner violence (IPV),
      achieving stability is likely as important for other groups, but can be
      challenging. Through our analysis of 41 interviews with women who have
      experienced low income and IPV, we argue that definitions of housing stability
      are multifaceted and for many centred on a shared understanding of the importance
      of creating an environment of "home". We found that obtaining housing that
      satisfied material needs was important to women. However, in asking women to
      define what housing stability meant to them, we found that other factors related
      to ontological security and the home, such as safety, community, and comfort,
      contributed to women's experiences of stability. Through our discussion of the
      importance these women placed on establishing stable homes, we argue that future
      research on women's experiences with housing stability and IPV should include
      definitions of stability that capture both material security and women's
      experiences with building emotionally stable homes.

PMID- 29323348
TI  - Mouse Antibody of IgM Class is Prone to Non-Enzymatic Cleavage between CH1 and
      CH2 Domains.
AB  - IgM is a multivalent antibody which evolved as a first line defense of adaptive
      immunity. It consists of heavy and light chains assembled into a complex
      oligomer. In mouse serum there are two forms of IgM, a full-length and a
      truncated one. The latter contains MU' chain, which lacks a variable region.
      Although MU' chain was discovered many years ago, its origin has not yet been
      elucidated. Our results indicate that MU' chain is generated from a full-length
      heavy chain by non-enzymatic cleavage of the protein backbone. The cleavage
      occurred specifically after Asn209 and is prevented by mutating this residue into
      any other amino acid. The process requires the presence of other proteins,
      preferentially with an acidic isoelectric point, and is facilitated by neutral or
      alkaline pH. This unique characteristic of the investigated phenomenon
      distinguishes it from other, already described, Asn-dependent protein reactions.
      A single IgM molecule is able to bind up to 12 epitopes via its antigen binding
      fragments (Fabs). The cleavage at Asn209 generates truncated IgM molecules and
      free Fabs, resulting in a reduced IgM valence and probably affecting IgM
      functionality in vivo.

PMID- 29323350
TI  - Regionalization of housing policies? An exploratory study of Andalusia, Catalonia
      and the Basque Country.
AB  - The Spanish home ownership sector has been hit hard by the economic crisis.
      Repossessions stand at around half a million in the period from 2008 to 2014.
      This article investigates how the authorities, both at the level of the Spanish
      state and of the autonomous communities (regions), have responded to this
      problem. We investigated whether they assist troubled home owners and aim to
      design a less risky housing system, with more (social) rental housing. Our
      research in Catalonia, the Basque Country and Andalusia shows that Autonomous
      Communities are playing an increasingly important role in this matter. This
      finding fits well with theories on the formation of regional varieties of
      welfare, which indicate that flaws of the central governments in providing social
      welfare, are increasingly addressed by regions. The Basque Country seems to be on
      the way of designing the most comprehensive system of housing policies of the
      three regions, including a strong Right to Housing. All three regions regard the
      mobilisation of the large vacant dwelling stock as an important means to provide
      more affordable rental housing. However, the owners are often unwilling and the
      three regions have proposed drastic measures, such as fines and even temporary
      expropriations. The central government resists such measures, because they might
      interfere with the proper working of the country's financial system. It shows
      that certain policy competences can never be totally isolated from other policy
      fields and multi-level distribution of competences makes it all the more complex.

PMID- 29323351
TI  - Ethnic differences in realising desires to leave urban neighbourhoods.
AB  - Selective mobility into and out of urban neighbourhoods is one of the main
      driving forces of segregation. Earlier research has found group differences in
      who wants to leave or who leaves certain types of neighbourhoods. A factor that
      has received little attention so far is that some residents will have a desire to
      leave their neighbourhood, but are unable to do so. If there are differences
      between population groups in the realisation of desires to leave the
      neighbourhood, this might lead to involuntary segregation. This paper uses a
      unique combination of register data and survey data. We combine data from a large
      housing survey in the Netherlands (WoON) with longitudinal register data from the
      Netherlands (SSD) which contains individual-level information on residential
      mobility histories. This allows us to study whether households with a desire to
      leave their neighbourhood do realise this desire and which households are
      successful in leaving which neighbourhoods. A more thorough insight in who wants
      to leave which neighbourhoods but is unable to do so will contribute to a better
      understanding of selective mobility and segregation. We find that ethnic
      minorities and low-income households are less likely to realise a desire to leave
      their neighbourhood. We expected that ethnic minorities would be especially
      unsuccessful in realising desires to leave minority concentration neighbourhoods;
      however, for none of the ethnic groups we found an effect of neighbourhood ethnic
      composition on the realisation of desires to leave.

PMID- 29323352
TI  - The end of mass homeownership? Changes in labour markets and housing tenure
      opportunities across Europe.
AB  - With continued economic growth and expanding mortgage markets, until recently the
      pattern across advanced economies was of growing homeownership sectors. The Great
      Financial Crisis (GFC) has however, undercut this growth resulting in the
      contraction of homeownership access in many countries and the revival of private
      renting. This paper argues that these tenure changes are not solely a consequence
      of the GFC, and therefore, reversible once long-term growth returns. Rather, they
      are the consequences of more fundamental changes especially in labour markets.
      The very financialisation that fuelled the growth of homeownership has also led
      to a hollowing out of well-paid, secure jobs-exactly those that fit best with the
      taking of housing loans. We examine longer-term declines in labour market
      security across Europe from before the GFC, identifying an underlying correlation
      between deteriorated labour market conditions and homeownership access for young
      adults. While variations exist across European countries, there is evidence of
      common trends. We argue that the GFC both accelerated pre-existing labour
      insecurity dynamics and brought an end to offsetting such dynamics through the
      expansion of credit access with the likelihood of a return to an era of
      widespread homeownership growth starkly decreased.

PMID- 29323353
TI  - Housing system reform: the opinion of advisory boards versus political reality in
      the Netherlands.
AB  - This paper describes to what extent a more or less collective feeling of urgency
      to reform the Dutch housing market is addressed in the political arena. By doing
      that, it sheds some light on the effectiveness and influence of academic research
      and recommendations on the political decision making process. We conclude that
      the suggestion of several advisory bodies to start a serious reform of the
      housing system in the Netherlands is, due to coalition considerations, almost
      fully neglected by the Dutch Government. Although there is a common understanding
      among experts and interest organisations in the Netherlands that the current
      housing systems needs radical changes, coalition politics in the Netherlands are
      apparently more important to explain current housing policies. We conclude that
      the effectiveness and influence of academic research and recommendations on the
      political decision making process was quite modest in the last couple of years
      and try to explain the gap between academic research and political decision
      making on Dutch housing policy.

PMID- 29323354
TI  - Utility indifference pricing of insurance catastrophe derivatives.
AB  - We propose a model for an insurance loss index and the claims process of a single
      insurance company holding a fraction of the total number of contracts that
      captures both ordinary losses and losses due to catastrophes. In this model we
      price a catastrophe derivative by the method of utility indifference pricing. The
      associated stochastic optimization problem is treated by techniques for piecewise
      deterministic Markov processes. A numerical study illustrates our results.

PMID- 29323355
TI  - Competition between social and market renting: a theoretical application of the
      structure-conduct-performance paradigm.
AB  - Housing policies in many countries have become more market orientated as the role
      of governments has shifted from the direct supply and funding of non-market
      housing towards the role of a regulator and facilitator. Central to this
      development is the notion that providers of social housing have to become more
      competitive. Arguably, these social housing changes have important implications
      for the relationship between social and market rented housing and thus the rental
      market as a whole. Conceptual frameworks that facilitate the understanding of
      this relationship are sparse commodities. This paper seeks to develop a
      theoretical framework that can be used to shed light on the conditions,
      processes, and effects of the new relation between the two rental tenures from an
      economic competition viewpoint. Therefore, this paper adapts the structure
      conduct-performance paradigm to rented housing and discusses the framework's
      applicability and value on a theoretical level.

PMID- 29323357
TI  - The distribution of housing wealth in 16 European countries: accounting for
      institutional differences.
AB  - Housing wealth is the largest source of household wealth, but we know little
      about the distribution of housing wealth and how institutions have shaped this
      distribution. Subsidies for homeownership, privatisation of social housing and
      mortgage finance liberalisation are likely to have influenced the distribution of
      housing wealth in recent decades. To examine their impact, we describe housing
      wealth inequalities across occupational classes for two birth cohorts aged fifty
      and older. The analysis is conducted across 16 European countries with divergent
      welfare states and housing systems using the fourth wave of the survey of health,
      ageing and retirement in Europe (SHARE; 2011/2012). Our results indicate that the
      expansion of homeownership in a market-based housing system is associated with a
      more unequal distribution of housing wealth across occupational classes, as an
      increasing number of 'marginal' owners are drawn into precarious homeownership.
      Such a pattern is not found in housing wealth accumulation regimes with a less
      market-based provision of housing. When the state or the family drive
      homeownership expansion, a de-coupling of labour market income and housing
      consumption results in a more equal distribution of housing wealth.

PMID- 29323358
TI  - Solvency II solvency capital requirement for life insurance companies based on
      expected shortfall.
AB  - This paper examines the consequences for a life annuity insurance company if the
      solvency II solvency capital requirements (SCR) are calibrated based on expected
      shortfall (ES) instead of value-at-risk (VaR). We focus on the risk modules of
      the SCRs for the three risk classes equity risk, interest rate risk and longevity
      risk. The stress scenarios are determined using the calibration method proposed
      by EIOPA in 2014. We apply the stress-scenarios for these three risk classes to a
      fictitious life annuity insurance company. We find that for EIOPA's current
      quantile 99.5% of the VaR, the stress scenarios of the various risk classes based
      on ES are close to the stress scenarios based on VaR. Might EIOPA choose to
      calibrate the stress scenarios on a smaller quantile, the longevity SCR is
      relatively larger and the equity SCR is relatively smaller if ES is used instead
      of VaR. We derive the same conclusion if stress scenarios are determined with
      empirical stress scenarios.

PMID- 29323359
TI  - Scale, mergers and efficiency: the case of Dutch housing corporations.
AB  - The efficiency of social housing providers is a contentious issue. In the
      Netherlands, there is a widespread belief that housing corporations have
      substantial potential for efficiency improvements. A related question is whether
      scale influences efficiency, since recent decades have shown a trend of mergers
      among corporations. This paper offers a framework to assess the effects of scale
      and mergers on the efficiency of Dutch housing corporations by using both a data
      envelopment analysis and a stochastic frontier analysis, using panel data for
      2001-2012. The results indicate that most housing corporations operate under
      diseconomies of scale, implying that merging would be undesirable in most cases.
      However, merging may have beneficial effects on pure technical efficiency as it
      forces organizations to reconsider existing practices. A data envelopment
      analysis indeed confirms this hypothesis, but these results cannot be replicated
      by a stochastic frontier analysis, meaning that the evidence for this effect is
      not robust.

PMID- 29323360
TI  - The mismatch between conventional house price modeling and regulated markets:
      insights from The Netherlands.
AB  - House price modeling has been frequently used to investigate the dynamics of
      housing markets, especially competitive markets; yet less attention has been
      given to markets that have experienced considerable interventions. The aim of
      this study is to demonstrate a mismatch between conventional house price models
      and the case of the Netherlands and to provide reasons of such mismatch. We first
      describe and classify the conventional house price models into asset-pricing
      house price model, stock-flow model, multi-period utility model, and repayment
      model. These models are subsequently applied to the Netherlands, where
      considerable government interventions took place. As expected, the empirical
      results are unsatisfactory to explain the Dutch house price development. The
      degree of mismatch of the repayment model and the multi-period utility model,
      however, seems to be fairly limited.

PMID- 29323361
TI  - Small population bias and sampling effects in stochastic mortality modelling.
AB  - We propose the use of parametric bootstrap methods to investigate the finite
      sample distribution of the maximum likelihood estimator for the parameter vector
      of a stochastic mortality model. Particular emphasis is placed on the effect that
      the size of the underlying population has on the distribution of the MLE in
      finite samples, and on the dependency structure of the resulting estimator: that
      is, the dependencies between estimators for the age, period and cohort effects in
      our model. In addition, we study the distribution of a likelihood ratio test
      statistic where we test a null hypothesis about the true parameters in our model.
      Finally, we apply the LRT to the cohort effects estimated from observed mortality
      rates for females in England and Wales and males in Scotland.

PMID- 29323362
TI  - A pH responsive AIE probe for enzyme assays.
AB  - By combining leucine (Leu) and tetraphenylethene (TPE), a pH-sensitive
      aggregation induced emission (AIE) probe TPE-Leu was developed. The aliphatic
      amine in TPE-Leu was more easily protonated under acidic conditions, which made
      TPE-Leu more water soluble. Therefore, the protonated AIE probe showed weak
      fluorescence under acidic conditions. When the pH was changed to basic
      conditions, it showed strong fluorescence due to the hydrophobic nature of TPE
      Leu. We demonstrated that the probe showed high selectivity toward pH changes
      with the coexistence of other potential species such as metal ions, redox agents,
      and biomolecules. In contrast, TPE-NH2 did not exhibit obvious pH-sensitive
      properties. Moreover, TPE-Leu was further utilized to develop a sensitive and
      selective sensing platform for urease and acetylcholinesterase (AChE) detection.
      The current study not only provides a new strategy for designing pH-sensitive
      fluorescent probes for bioassays but also broadens the applications of AIE
      probes.

PMID- 29323363
TI  - High-efficiency X-ray luminescence in Eu3+-activated tungstate nanoprobes for
      optical imaging through energy transfer sensitization.
AB  - X-ray luminescence optical imaging has been recognized as a powerful technique
      for medical diagnosis due to its deep penetration and low auto-fluorescence in
      tissues. However, the low luminescence efficiency of current X-ray luminescence
      nanoprobes remains a major hurdle for sensitive bioimaging in practical medical
      applications. Here we present a new kind of energy transfer-sensitized X-ray
      luminescence nanoprobe (PEG-NaGd(WO4)2:Eu) for highly effective optical
      bioimaging. Under X-ray excitation, the tungstate host absorbs the X-ray photons
      and then transfers the energy to the Eu3+ luminescence center, thus enhancing the
      luminescence efficiency of the nanoprobes for high sensitivity optical in vivo
      imaging. Moreover, the shortened T1 relaxation response of Gd3+ ions and X-ray
      attenuation capability of W atoms enable the nanoprobes to serve as efficient
      contrast agents for magnetic resonance imaging (MRI) and computed tomography (CT)
      imaging. Therefore, combined with the MRI, CT and X-ray luminescence imaging
      capabilities, the present PEG-NaGd(WO4)2:Eu nanoprobes could be used as promising
      multimodal imaging contrast agents in biological systems.

PMID- 29323364
TI  - Graphene template-induced growth of single-crystalline gold nanobelts with high
      structural tunability.
AB  - Assembling Au nanocrystals with tunable dimensions and shapes on graphene
      templates has attracted increasing attention recently. However, directly growing
      anisotropic Au nanobelts on a graphene support has been rarely reported. Here, a
      facile, one-pot, and surfactant-free route is demonstrated to synthesize well
      defined Au nanobelts with the induction of a multilayer graphene (mlG) template.
      The obtained Au nanobelts are single-crystalline with a preferable (111)
      orientation. More importantly, their structural evolution starting from Au
      clusters is systematically investigated using scanning electron microscopy (SEM)
      and transmission electron microscopy (TEM). The results confirm that mlG
      consistently induces the growth of Au nanobelts from nucleation to the growth
      completion. The interfacial interaction between Au atoms and the graphene lattice
      is a predominant factor to direct the shapes and structures of Au nanocrystals,
      which makes the structures of Au nanobelts highly tunable with the surface
      modification of the mlG template. The assembly of mlG-Au nanobelts also presents
      extraordinary detection sensitivity when employed as a flexible surface-enhanced
      Raman scattering (SERS) substrate, suggesting their great potential application
      in high-performance sensors. This report strengthens the fundamental
      understanding of the interactions between noble metals and carbon interfaces,
      which paves the way to construct and manipulate the complex structures of metals
      on graphitic substrates.

PMID- 29323365
TI  - Iridium complexes of perimidine-based N-heterocyclic carbene pincer ligands via
      aminal C-H activation.
AB  - The reactions of N,N'-bis(phosphinomethyl)dihydroperimidine pro-ligands
      H2C(NCH2PR2)2C10H6-1,8 (R = Ph 1a, R = Cy 1b) with iridium(i) substrates have
      been investigated and shown to readily result in chelate-assisted C-H activation
      processes. The reaction of 1b with [Ir2Cl2(COE)4] (COE = cyclo-octene) affords
      the 18-electron iridium(iii) dihydrido complex [IrH2Cl{kappa3-C,P,P'
      C(NCH2PCy2)2C10H6}], which forms [IrHCl2{kappa3-C,P,P'-C(NCH2PCy2)2C10H6}] under
      acidic (HCl) conditions. In contrast, reaction of 1a with [Ir2Cl2(COD)2] (COD =
      1,5-cyclo-octadiene) affords the complex [IrCl(COD){kappa2-P,P'
      H2C(NCH2PPh2)2C10H6}], thermolysis of which affords cyclo-octene and the pincer
      NHC complex [IrCl{kappa3-C,P,P'-C(NCH2PPh2)2C10H6}]. The reaction of 1a with two
      equivalents of [Ir2Cl2(COD)2] provides the binuclear complex [Ir2{MU
      H2C(NCH2PPh2)2C10H6}Cl2(COD)2] which is also observed to accumulate and then
      dissipate during the preceding thermolysis. Related binuclear complexes [M2{MU
      H2C(NCH2PPh2)2C10H6}Cl4(eta-C5Me5)2] (M = Ir, Rh) which obviate C-H activation
      were similarly synthesised.

PMID- 29323366
TI  - Largely enhanced dielectric constant of PVDF nanocomposites through a core-shell
      strategy.
AB  - Core-shell structured TiO2@carbon nanowire (TiO2@C NW) hybrids with different
      carbon shell thicknesses were synthesized by a combination of a hydrothermal
      reaction and the chemical vapor deposition (CVD) method. Pristine TiO2 NWs with a
      high aspect ratio were obtained by a hydrothermal reaction and the as-synthesized
      TiO2 NWs were subsequently employed as the template for carbon shell deposition
      during the CVD procedure. The obtained TiO2@C NW hybrids have a uniform carbon
      shell and the thickness of the carbon shell could be precisely designed from 4 nm
      to 40 nm by controlling the deposition time. With the help of solution and melt
      blending methods, the TiO2@C NW hybrids were subsequently incorporated into the
      PVDF matrix to fabricate TiO2@C NWs/PVDF nanocomposites, which exhibit a similar
      percolative dielectric behavior to that reported in other percolative
      nanocomposites. Moreover, the dielectric properties of the TiO2@C NWs/PVDF
      nanocomposites could be accurately adjusted by tuning the carbon shell thickness
      of the TiO2@C NW hybrids. The highest dielectric constant (2171) of the TiO2@C
      NWs/PVDF nanocomposites is 80 times larger than those of the pristine TiO2-filled
      ones at the same filler loading, and 241 times higher than that of the pure PVDF
      matrix. The enhanced dielectric performance could be attributed to the improved
      interfacial polarizations of TiO2/C and C/PVDF interfaces. This approach provides
      an interesting alternative to fabricate high-performance dielectric
      nanocomposites for practical applications in the electronic industry.

PMID- 29323369
TI  - Organic semiconductor perylenetetracarboxylic diimide (PTCDI) electrodes for
      electrocatalytic reduction of oxygen to hydrogen peroxide.
AB  - Hydrogen peroxide is one of the most important industrial chemicals and there is
      great demand for the production of H2O2 using more sustainable and
      environmentally benign methods. We show electrochemical production of H2O2 by the
      reduction of O2, enabled by an organic semiconductor catalyst, N,N'-dimethyl
      perylenetetracarboxylic diimide (PTCDI). We make PTCDI cathodes that are capable
      of stable and reusable operation in aqueous electrolytes in a pH range of 1-13
      with a catalytic figure of merit as high as 26 kg H2O2 per g catalyst per h.
      These performance and stability open new avenues for organic small molecule
      semiconductors as electrocatalysts.

PMID- 29323367
TI  - Quantitative mass spectrometry imaging of glutathione in healthy and cancerous
      hen ovarian tissue sections by infrared matrix-assisted laser desorption
      electrospray ionization (IR-MALDESI).
AB  - A quantitative mass spectrometry imaging (QMSI) method for absolute
      quantification of glutathione (GSH) in healthy and cancerous hen ovarian tissues
      using infrared matrix-assisted laser desorption electrospray ionization (IR
      MALDESI) is presented. Using this technique, the ion abundance of GSH was
      normalized to that of a structural analogue, which was sprayed on the slide prior
      to mounting the tissue sections. This normalization strategy significantly
      improved the voxel-to-voxel variability; the variability is attributed to the
      overall ionization process. Subsequently, a series of calibration spots of stable
      isotope-labeled (SIL) GSH were pipetted on top of the tissue to construct a
      spatial calibration curve, and calculate the concentration of GSH in both tissue
      sections. The QMSI results were verified by LC-MS/MS quantification of GSH for
      the same tissues. GSH was extracted from tissue sections in a slightly acidic
      buffer and was then alkylated using N-ethylmaleimide to minimize autoxidation of
      GSH to glutathione disulfide. The alkylated GSH was separated from other
      contaminants using reversed phase liquid chromatography (RPLC) coupled to a
      triple quadrupole mass spectrometer, and the z-ion transition of NEM-GSH was used
      to quantify GSH in each tissue section. While the absolute values obtained using
      IR-MALDESI QMSI and LC-MS/MS were different, a ~2-fold increase in the
      concentration of GSH in cancer tissue compared to the healthy tissue was observed
      using both techniques. Possible reasons for the difference between absolute
      concentration values obtained using IR-MALDESI QMSI and LC-MS/MS are also
      discussed.

PMID- 29323370
TI  - Photocatalytic partial oxidation of limonene to 1,2 limonene oxide.
AB  - The silylation of crystalline TiO2 P25, commonly used for photocatalytic
      degradation of pollutants, results in an exceptionally selective catalyst for the
      aerobic limonene epoxidation to 1,2-limonene oxide under solar light irradiation.
      The hypothesized mechanism involves the singlet oxygen generated through energy
      transfer from the excited TiO2 to adsorbed O2 molecules. The reaction product is
      the valued precursor of bio-based poly(limonene carbonate), a thermoplastic
      polymer of superior thermal and optical properties whose industrial production is
      in need of an efficient green synthesis of limonene oxide.

PMID- 29323371
TI  - Combining experimental and modelling approaches to study the sources of reactive
      species induced in water by the COST RF plasma jet.
AB  - The vast biomedical potential of cold atmospheric pressure plasmas (CAPs) is
      governed by the formation of reactive species. These biologically active species
      are formed upon the interaction of CAPs with the surroundings. In biological
      milieu, water plays an essential role. The development of biomedical CAPs thus
      requires understanding of the sources of the reactive species in aqueous media
      exposed to the plasma. This is especially important in case of the COST RF plasma
      jet, which is developed as a reference microplasma system. In this work, we
      investigated the formation of the OH radicals, H atoms and H2O2 in aqueous
      solutions exposed to the COST plasma jet. This was done by combining experimental
      and modelling approaches. The liquid phase species were analysed using UV-Vis
      spectroscopy and spin trapping with hydrogen isotopes and electron paramagnetic
      resonance (EPR) spectroscopy. The discrimination between the species formed from
      the liquid phase and the gas phase molecules was performed by EPR and 1H-NMR
      analyses of the liquid samples. The concentrations of the reactive species in the
      gas phase plasma were obtained using a zero-dimensional (0D) chemical kinetics
      computational model. A three-dimensional (3D) fluid dynamics model was developed
      to provide information on the induced humidity in the plasma effluent. The
      comparison of the experimentally obtained trends for the formation of the species
      as a function of the feed gas and effluent humidity with the modelling results
      suggest that all reactive species detected in our system are mostly formed in the
      gas phase plasma inside the COST jet, with minor amounts arising from the plasma
      effluent humidity.

PMID- 29323372
TI  - Highly stable lipid-encapsulation of fluorescent nanodiamonds for bioimaging
      applications.
AB  - Highly stable lipid-encapsulated fluorescent nanodiamonds (FNDs) are produced by
      photo-crosslinking of diacetylene-containing lipids physically attached to the
      FND surface. Not only is this coating method simple and fast, but also it gives
      the FND-lipid hybrids favorable properties for bioapplications. The hybrids are
      useful as fluorescent biolabels as well as fiducial markers for correlative light
      and electron microscopy.

PMID- 29323373
TI  - New electron delocalization tools to describe the aromaticity in porphyrinoids.
AB  - The role of aromaticity in porphyrinoids is a current subject of debate due to
      the intricate structure of these macrocycles, which can adopt Huckel, Mobius and
      even figure-eight conformers. One of the main challenges in these large pi
      conjugated structures is identifying the most conjugated pathway because, among
      aromaticity descriptors, there are very few that can be applied coherently to
      this variety of conformers. In this paper, we have investigated the conjugated
      pathways in nine porphyrinoid compounds using several aromaticity descriptors,
      including BLA, BOA, FLU and HOMA, as well as the recently introduced AV1245 and
      AVmin indices. All the indices agree on the general features of these compounds,
      such as the fulfillment of Huckel's rule or which compounds should be more or
      less aromatic from the series. However, our results evince the difficulty of
      finding the most aromatic pathway in the macrocycle for large porphyrinoids. In
      fact, only AVmin is capable of recognizing the annulene pathway as the most
      aromatic one in the nine studied structures. Finally, we study the effect of the
      exchange in DFT functionals on the description of the aromaticity of the
      porphyrinoids. The amount of exact exchange quantitatively changes the picture
      for most aromaticity descriptors, AVmin being the only exception that shows the
      same qualitative results in all cases.

PMID- 29323374
TI  - Frustrated Lewis pairs incorporating the bifunctional Lewis acid 1,1'
      fc{B(C6F5)2}2: reactivity towards small molecules.
AB  - Applications of the bifunctional ferrocenediyl Lewis acid 1,1'-fc{B(C6F5)2}2 in
      frustrated Lewis pair (FLP) chemistry are described. The coordination (or
      otherwise) of a range of sterically encumbered C-, N- and P-centred Lewis bases
      has been investigated, with lutidine, tetramethylpiperidine, PPh3, PtBu3 and the
      expanded ring carbene 6Dipp being found to be sterically incapable of coordinate
      bond formation. The chemistry of a range of these FLPs in the presence of H2O,
      NH3, CO2 and cyclohexylisocyanate (CyNCO) has been investigated, with the
      patterns of reactivity identified including simple coordination chemistry, E-H
      bond cleavage and C-B insertion.

PMID- 29323375
TI  - Confinement of polysulfides within bi-functional metal-organic frameworks for
      high performance lithium-sulfur batteries.
AB  - A lithium-sulfur (Li-S) battery is regarded as the most promising candidate for
      next generation energy storage systems, because of its high theoretical specific
      capacity (1675 mA h g-1) and specific energy (2500 W h kg-1), as well as the
      abundance, low cost and environmental benignity of sulfur. However, the soluble
      polysulfides Li2Sx (4 <= x <= 8) produced during the discharge process can cause
      the so-called "shuttle effect" and lead to low coulombic efficiency and rapid
      capacity fading of the batteries, which seriously restrict their practical
      application. Using porous materials as hosts to immobilize the polysulfides is
      proved to be an effective strategy. In this article, a dual functional cage-like
      metal-organic framework (Cu-MOF), Cu-TDPAT, combining the Lewis basic sites from
      the nitrogen atoms of the ligand H6TDPAT with the Lewis acidic sites from Cu(ii)
      open metal sites (OMSs), was employed as the sulfur host in a Li-S battery for
      lithium ions and polysulfide anions (Sx2-). In addition, the size of nano-Cu
      TDPAT was also optimized by microwave synthesis to reduce the internal resistance
      of the batteries. The electrochemical test results showed that the optimized Cu
      TDPAT material can efficiently confine the polysulfides within the MOF, and the
      resultant porous S@Cu-TDPAT composite cathode material with the size of 100 nm
      shows good cycling performance with a reversible capacity of about 745 mA h g-1
      at 1C (1C = 1675 mA g-1) after 500 cycles, to the best of our knowledge, which is
      higher than those of all reported S@MOF cathode materials. The DFT calculation
      and XPS data indicate that the good cycling performance mainly results from the
      dual functional binding sites (that is, Lewis acid and base sites) in nanoporous
      Cu-TDPAT, providing the comprehensive and robust interaction with the
      polysulfides to overcome their dissolution and diffusion into the electrolyte.
      Clearly, our work provides a good example of designing MOFs with suitable
      interaction sites for the polysulfides to achieve S@MOF cathode materials with
      excellent cycling performance by multiple synergistic effects between nanoporous
      host MOFs and the polysulfides.

PMID- 29323376
TI  - A multifunctional wearable sensor based on a graphene/inverse opal cellulose film
      for simultaneous, in situ monitoring of human motion and sweat.
AB  - A multifunctional, wearable sensor based on a reduced oxide graphene (rGO) film
      onto a porous inverse opal acetylcellulose (IOAC) film has been developed and can
      perform simultaneous, in situ monitoring of various human motions and ion
      concentrations in sweat. The rGO film is used as a strain-sensing layer for
      monitoring human motion via its resistance change, whereas the porous IOAC film
      is used as a flexible microstructured substrate not only for high sensitive
      motion sensing, but also for collection and analysis of ion concentrations in
      sweat by its simple colorimetric changes or reflection-peak shifts. Studies on
      humans demonstrated that the devices have excellent capability for monitoring
      various human motions, such as finger bending motion, wrist bending motion, head
      rotation motion and various small-scale motions of the throat. Simultaneous, in
      situ analysis of the ion concentration in sweat during these motions shows that
      the IOAC substrate can detect a wide range of NaCl concentrations in sweat from
      normal 30 to 680 mM under the conditions of severe dehydration. This
      investigation provides new horizons toward the design and fabrication of
      multifunctional, wearable health monitoring devices and the proposed wearable
      sensor shows promising applications in healthcare and preventive medicine.

PMID- 29323377
TI  - A novel strategy for thermometry based on the temperature-induced red shift of
      the charge transfer band edge.
AB  - We report a novel strategy for optical temperature sensing using the temperature
      induced red shift of the charge transfer band (CTB) edge of the VO43- groups in
      GdVO4:5% Sm3+. Excitation spectra were recorded at a series of temperatures
      ranging from 300 to 480 K. It is demonstrated that an excitation intensity of
      around 360 nm corresponding to the tail of the CTB and an excitation intensity of
      407.6 nm corresponding to the 6H5/2 -> 4F7/2 transition of Sm3+ exhibit opposite
      temperature dependence. Based on this, the relative sensitivity was obtained to
      be 3313/T2 in our investigated temperature range, which is remarkable progress
      compared with the optical temperature sensors reported previously. We believe
      that this work broadens the pathway for the design of highly sensitive
      temperature sensing materials.

PMID- 29323378
TI  - From ligand exchange to reaction intermediates: what does really happen during
      the synthesis of emissive complexes?
AB  - In situ monitoring of the formation of emissive complexes is essential to enable
      the development of rational synthesis protocols, to provide accurate control over
      the generation of structure-related properties (such as luminescence) and to
      facilitate the development of new compounds. In situ luminescence analysis of
      coordination sensors (ILACS) utilizes the sensitivity of the spectroscopic
      properties of lanthanide ions to their coordination environment to detect
      structural changes during crystallization processes. Here, ILACS was utilized to
      monitor the formation of [Eu(bipy)2(NO3)3] (bipy = 2,2'-bipyridine) during co
      precipitation synthesis. Validity of the ILACS results was ensured by concomitant
      utilization of in situ monitoring of other reaction parameters, including in situ
      measurements of pH value, ionic conductivity, and infrared spectra, as well as ex
      situ and synchrotron-based in situ X-ray diffraction analyses. Gradual
      desolvation of the Eu3+ ions and attachment of ligands were detected by an
      exponential increase of the intensity of the 5D0 -> 7FJ (J = 0-4) transitions in
      the emission spectrum. Additionally, the in situ emission spectra show a decrease
      in the crystallization rate and an increase in the induction time in response to
      a reduction in the concentration of the starting solutions from 12 mM until
      crystallization ceased at starting reactant concentrations <6 mM. An increase to
      a three-fold higher concentration leads to the formation of a reaction
      intermediate, and its stability was determined to be highly concentration
      dependent. The in situ luminescence measurements also demonstrated the existence
      of a ligand exchange process within the [Eu(bipy)2(NO3)3] complex upon addition
      of a phen (phen = 1,10'-phenanthroline) solution and the generation of a new phen
      containing emissive complex. In attempting to solve the structure of this new
      phen-containing complex, a different, but nevertheless previously unsynthesized
      complex, [Eu(phen)2(NO3)3]bipy, was obtained, which shows characteristic Eu3+
      luminescence in the red spectral range.

PMID- 29323379
TI  - Chemical profiling of two congeneric sea mat corals along the Brazilian coast:
      adaptive and functional patterns.
AB  - Metabolomic profiles were explored to understand environmental and taxonomic
      influences on the metabolism of two congeneric zoanthids, Palythoa caribaeorum
      and P. variabilis, collected across distinct geographical ranges. Integrated mass
      spectrometry data suggested the major influence of geographical location on
      chemical divergence when compared to species differentiation.

PMID- 29323380
TI  - Aldehyde-functionalized metal-organic frameworks for selective sensing of
      homocysteine over Cys, GSH and other natural amino acids.
AB  - A novel aldehyde-functionalized porous metal-organic framework (MOF) material has
      been constructed that can act as the first example of MOF-implicated sensors for
      discriminating Hcy from natural amino acids and even thiol-related peptides (GSH)
      with high sensitivity (LOD = 40 nM). The sensing mechanism is also discussed.

PMID- 29323381
TI  - Lifted graphene nanoribbons on gold: from smooth sliding to multiple stick-slip
      regimes.
AB  - Graphene nanoribbons (GNRs) physisorbed on a Au(111) surface can be picked up,
      lifted at one end, and made to slide by means of the tip of an atomic-force
      microscope. The dynamic transition from smooth sliding to multiple stick-slip
      regimes, the pushing/pulling force asymmetry, the presence of pinning, and its
      origin are real frictional processes in a nutshell, in need of a theoretical
      description. To this purpose, we conduct classical simulations of frictional
      manipulations of a 30 nm-long GNR, one end of which is pushed or pulled
      horizontally while held at different heights above the Au surface. These
      simulations allow us to clarify theoretically the emergence of stick-slip
      originating from the short 1D edges rather than the 2D "bulk", the role of
      adhesion, of lifting, and of graphene bending elasticity in determining the GNR
      sliding friction. The understanding obtained in this simple context is of
      additional value for more general cases.

PMID- 29323382
TI  - Probing transcription factor binding activity and downstream gene silencing in
      living cells with a DNA nanoswitch.
AB  - Transcription factor DNA binding activity is of pivotal importance in living
      systems because of its primary involvement in the regulation of genetic
      machinery. The analysis of transient expression levels of transcription factors
      in response to a certain cell status is a powerful means for investigating
      cellular dynamics at the biomolecular level. Herein, a DNA-based molecular switch
      that enables probing of transcription factor DNA binding activity is directly
      used in living cells. We demonstrate that the DNA nanoswitch allows for dynamic
      fluorescence imaging of NF-kappaB and quantification of downstream gene silencing
      in real time. The present strategy is based on a functional DNA nanodevice that
      transduces, through a binding-induced conformational change, the recognition of a
      specific transcription factor into a fluorescent signal. In addition, stochastic
      optical resolution microscopy, a super-resolution microscopy technique, is used
      to track the internalization and intracellular trafficking of the DNA nanodevice
      with high spatial resolution. Overall, it has been shown that a rationally
      designed DNA nanodevice can be used to achieve rapid, simple, and cost-effective
      real-time determination of transcription factor binding activity and downstream
      gene silencing.

PMID- 29323383
TI  - Field-dependent dynamic responses from dilute magnetic nanoparticle dispersions.
AB  - The response of magnetic nanoparticles (MNPs) to an oscillating magnetic field
      outside the linear response region is important for several applications
      including magnetic hyperthermia, magnetic resonance imaging and biodetection. The
      size and magnetic moment are two critical parameters for the performance of a
      colloidal MNP dispersion. We present and demonstrate the use of optomagnetic (OM)
      and AC susceptibility (ACS) measurements vs. frequency and magnetic field
      strength to obtain the size and magnetic moment distributions including the
      correlation between the distributions. The correlation between the size and the
      magnetic moment contains information on the morphology and intrinsic structure of
      the particle. In OM measurements, the variation of the second harmonic light
      transmission through a dispersion of MNPs is measured in response to an
      oscillating magnetic field. We solve the Fokker-Planck equations for MNPs with a
      permanent magnetic moment, and develop analytical approximations to the ACS and
      the OM signals that also account for the change in the curve shapes with
      increasing field strength. Further, we describe the influence of induced magnetic
      moments on the signals, by solving the Fokker-Planck equation for particles,
      which apart from the permanent magnetic moment may also have an induced magnetic
      moment and shape anisotropy. Using the results from the Fokker-Planck
      calculations we fit ACS and OM measurements on two multi-core particle systems.
      The obtained fit parameters also describe the correlations between the magnetic
      moment and size of the particles. From such an analysis on a commercially
      available polydisperse multicore particle system with an average particle size of
      80 nm, we find that the MNP magnetic moment is proportional to the square root of
      the hydrodynamic size.

PMID- 29323384
TI  - Tracking iron-associated proteomes in pathogens by a fluorescence approach.
AB  - Porphyromonas gingivalis is a key oral anaerobic bacterium involved in human
      periodontitis, which may affect up to 15% adults worldwide. Using the membrane
      permeable fluorescent probe Fe-TRACER, we identified 17 iron-associated proteins
      in Porphyromonas gingivalis. We demonstrated the specific binding of the probe
      towards iron-associated proteins using transferrin as an example and provided an
      X-ray structure of the fluorescent probe-bound transferrin. Our study provides a
      basis for the understanding of iron homeostasis in pathogens, and our approach
      based on the integration of fluorescence imaging with proteomics and
      bioinformatics can be readily extended to mine other metalloproteomes in
      microbials.

PMID- 29323385
TI  - 2D end-to-end carbon nanotube conductive networks in polymer nanocomposites: a
      conceptual design to dramatically enhance the sensitivities of strain sensors.
AB  - New generation wearable devices require mechanically compliant strain sensors
      with a high sensitivity in a full detecting range. Herein, novel 2D end-to-end
      contact conductive networks of multi-walled carbon nanotubes (MWCNTs) were
      designed and realized in an ethylene-alpha-octene block copolymer (OBC) matrix.
      The prepared strain sensor showed a high gauge factor (GF) of 248 even at a small
      strain (5%) and a linear resistance response throughout the whole strain range.
      The sensors also exhibited very good stretchability up to 300% and high cycling
      durability. This novel design solved the intrinsic problem of sensors based on
      carbon nanotube bundles, i.e., a long sliding phase before the disconnection of
      CNTs in a cost-effective and scalable way. This study rationalizes the 2D end-to
      end contact concept to improve the sensitivity of the existing sensors and has
      great potential to be used in a wide variety of polymer based sensors.

PMID- 29323386
TI  - Highly robust, uniform and ultra-sensitive surface-enhanced Raman scattering
      substrates for microRNA detection fabricated by using silver nanostructures grown
      in gold nanobowls.
AB  - Highly sensitive and reproducible surface enhanced Raman spectroscopy (SERS)
      requires not only a nanometer-level structural control, but also superb
      uniformity across the SERS substrate for practical imaging and sensing
      applications. However, in the past, increased reproducibility of the SERS signal
      was incompatible with increased SERS sensitivity. This work presents multiple
      silver nanocrystals inside periodically arrayed gold nanobowls (SGBs) via an
      electrochemical reaction at an overpotential of -3.0 V (vs. Ag/AgCl). The gaps
      between the silver nanocrystals serve as hot spots for SERS enhancement, and the
      evenly distributed gold nanobowls lead to a high device-to-device signal
      uniformity. The SGBs on the large sample surface exhibit an excellent SERS
      enhancement factor of up to 4.80 * 109, with excellent signal uniformity (RSD <
      8.0 +/- 2.5%). Furthermore, the SGBs can detect specific microRNA (miR-34a),
      which plays a widely acknowledged role as biomarkers in diagnosis and treatment
      of diseases. Although the small size and low abundance of miR-34a in total RNA
      samples hinder their detection, by utilizing the advantages of SGBs in SERS
      sensing, reliable and direct detection of human gastric cancer cells has been
      successfully accomplished.

PMID- 29323387
TI  - Synergistic effects of stellated fibrous mesoporous silica and synthetic dsRNA
      analogues for cancer immunotherapy.
AB  - Stellated fibrous mesoporous silica nanospheres significantly improve the
      cellular uptake of cancer antigen and the maturation of bone marrow derived
      dendritic cells in vitro. Moreover, the combination of poly(I:C) with stellated
      fibrous MS nanospheres markedly decreases the necessary dose of poly(I:C) for
      anti-tumor immunity, and thus opens new opportunities for the future clinical
      application of poly(I:C) in cancer immunotherapy.

PMID- 29323388
TI  - A novel thermal detection method based on molecularly imprinted nanoparticles as
      recognition elements.
AB  - Molecularly Imprinted Polymers (MIPs) are synthetic receptors that are able to
      selectively bind their target molecule and, for this reason, they are currently
      employed as recognition elements in sensors. In this work, MIP nanoparticles
      (nanoMIPs) are produced by solid-phase synthesis for a range of templates with
      different sizes, including a small molecule (biotin), two peptides (one derived
      from the epithelial growth factor receptor and vancomycin) and a protein
      (trypsin). NanoMIPs are then dipcoated on the surface of thermocouples that
      measure the temperature inside a liquid flow cell. Binding of the template to the
      MIP layer on the sensitive area of the thermocouple tip blocks the heat-flow from
      the sensor to the liquid, thereby lowering the overall temperature measured by
      the thermocouple. This is subsequently correlated to the concentration of the
      template, enabling measurement of target molecules in the low nanomolar regime.
      The significant improvement in the limit of detection (a magnitude of three
      orders compared to previously used MIP microparticles) can be attributed to their
      high affinity, enhanced conductivity and increased surface-to-volume ratio. It is
      the first time that these nanosized recognition elements are used in combination
      with thermal detection, and it is the first report on MIP-based thermal sensors
      for determining protein levels. The developed thermal sensors have a high
      selectivity, fast measurement time (<5 min), and data analysis is
      straightforward, which makes it possible to monitor biomolecules in real-time.
      The set of biomolecules discussed in this manuscript show that it is possible to
      cover a range of template molecules regardless of their size, demonstrating the
      general applicability of the biosensor platform. In addition, with its high
      commercial potential and biocompatibility of the MIP receptor layer, this is an
      important step towards sensing assays for diagnostic applications that can be
      used in vivo.

PMID- 29323389
TI  - Theoretical insight into the regioselective ring-expansions of bicyclic
      aziridinium ions.
AB  - Transient bicyclic aziridinium ions are known to undergo ring-expansion
      reactions, paving the way to functionalized nitrogen-containing heterocycles. In
      this study, the regioselectivity observed in the ring-expansion reactions of 1
      azoniabicyclo[n.1.0]alkanes was investigated from a computational viewpoint to
      study the ring-expansion pathways of two bicyclic systems with different ring
      sizes. Moreover, several nucleophiles leading to different experimental results
      were investigated. The effect of solvation was taken into account using both
      explicit and implicit solvent models. This theoretical rationalization provides
      valuable insight into the observed regioselectivity and may be used as a
      predictive tool in future studies.

PMID- 29323390
TI  - Bimetal-organic frameworks for functionality optimization: MnFe-MOF-74 as a
      stable and efficient catalyst for the epoxidation of alkenes with H2O2.
AB  - In this work, we synthesized a series of microcrystalline MnxN100-x-MOF-74 (N =
      Fe, Co and Ni) materials by a one-pot reaction. Powder X-ray diffraction (PXRD)
      patterns of MnxN100-x-MOF-74 matched well with those of single-metal MOF-74, and
      the scanning electron microscopy (SEM) images exhibited homogeneous
      nanocrystallites aggregated together. The amounts and dispersion of metals were
      analyzed by using inductively coupled plasma (ICP) and energy-dispersive X-ray
      spectroscopy (EDS), separately. MnxN100-x-MOF-74 could remain crystalline and
      efficiently catalyze the epoxidation of alkenes in DMF with NaHCO3 and 30% H2O2.
      In particular, Mn29.39Fe70.61-MOF-74 can achieve almost 100% conversion for
      styrene with 95.0% selectivity towards styrene oxide and be reused at least five
      times without loss of activity.

PMID- 29323391
TI  - Growth of regular nanometric molecular arrays on a functional 2D template based
      on a chemical guest-host approach.
AB  - A regular 2D array of crown molecules, which would spontaneously self-assemble
      into disordered molecular clusters, is obtained by exploiting a guest-host
      process, based on the chemical affinity between amino and carboxylic groups on a
      gold surface. First a carboxylic organic template is formed, which then serves as
      a host for amino-functionalized crown molecules. The amino-carboxylic interaction
      thereby drives the formation of a monolayer of guest molecules, regularly
      distributed at the nanometer scale, preventing their aggregation in unordered
      clusters observed on a bare gold surface. This method, which can be applied to
      other guest molecules, represents a novel route to overcome the shape-matching
      requirements of the standard guest-host architectures. Furthermore, it is
      intrinsically selective, due to the chemical nature of the anchoring process.

PMID- 29323392
TI  - High-Q and highly reproducible microdisks and microlasers.
AB  - High quality (Q) factor microdisks are fundamental building blocks of on-chip
      integrated photonic circuits and biological sensors. The resonant modes in
      microdisks circulate near their boundaries, making their performances strongly
      dependent upon surface roughness. Surface-tension-induced microspheres and
      microtoroids are superior to other dielectric microdisks when comparing Q
      factors. However, most photonic materials such as silicon and negative
      photoresists are hard to be reflowed and thus the realizations of high-Q
      microdisks are strongly dependent on electron-beam lithography. Herein, we
      demonstrate a robust, cost-effective, and highly reproducible technique to
      fabricate ultrahigh-Q microdisks. By using silica microtoroids as masks, we have
      successfully replicated their ultrasmooth boundaries in a photoresist via
      anisotropic dry etching. The experimentally recorded Q factors of passive
      microdisks can be as large as 1.5 * 106. Similarly, ultrahigh Q microdisk lasers
      have also been replicated in dye-doped polymeric films. The laser linewidth is
      only 8 pm, which is limited by the spectrometer and is much narrower than that in
      previous reports. Meanwhile, high-Q deformed microdisks have also been fabricated
      by controlling the shape of microtoroids, making the internal ray dynamics and
      external directional laser emissions controllable. Interestingly, this technique
      also applies to other materials. Silicon microdisks with Q > 106 have been
      experimentally demonstrated with a similar process. We believe this research will
      be important for the advances of high-Q micro-resonators and their applications.

PMID- 29323393
TI  - Nano-beam and nano-target effects in ion radiation.
AB  - Full three dimensional (3D) simulations of ion implantation are necessary in a
      wide range of nanoscience and nanotechnology applications to capture the
      increasing effect of ion leakage out of surfaces. Using a recently developed 3D
      Monte Carlo simulation code IM3D, we first quantify the relative error of the 1D
      approach in three applications of nano-scale ion implantation: (1) nano-beam for
      nitrogen-vacancy (NV) center creation, (2) implantation of nanowires to fabricate
      p-n junctions, and (3) irradiation of nano-pillars for small-scale mechanical
      testing of irradiated materials. Because the 1D approach fails to consider the
      exchange and leakage of ions from boundaries, its relative error increases
      dramatically as the beam/target size shrinks. Lastly, the "Bragg peak"
      phenomenon, where the maximum radiation dose occurs at a finite depth away from
      the surface, relies on the assumption of broad beams. We discovered a topological
      transition of the point-defect or defect-cluster distribution isosurface when one
      varies the beam width, in agreement with a previous focused helium ion beam
      irradiation experiment. We conclude that full 3D simulations are necessary if
      either the beam or the target size is comparable or below the SRIM longitudinal
      ion range.

PMID- 29323394
TI  - Box-like gel capsules from heterostructures based on a core-shell MOF as a
      template of crystal crosslinking.
AB  - New polymer capsules (PCs) were obtained using a crystal crosslinking (CC) method
      on core-shell MOF crystals. The latter are based on the epitaxial growth of two
      isostructural coordination polymers which are then selectively crosslinked.
      Decomposition of the non-reticulated phase leads to new PCs, possessing a well
      defined hollow cubic shape reflecting the heterostructure of the template.

PMID- 29323395
TI  - Self-powered implantable electronic-skin for in situ analysis of urea/uric-acid
      in body fluids and the potential applications in real-time kidney-disease
      diagnosis.
AB  - As the concentration of different biomarkers in human body fluids are an
      important parameter of chronic disease, wearable biosensors for in situ analysis
      of body fluids with high sensitivity, real-time detection, flexibility and
      biocompatibility have significant potential therapeutic applications. In this
      paper, a flexible self-powered implantable electronic-skin (e-skin) for in situ
      body fluids analysis (urea/uric-acid) as a real-time kidney-disease diagnoser has
      been proposed based on the piezo-enzymatic-reaction coupling process of ZnO
      nanowire arrays. It can convert the mechanical energy of body movements into a
      piezoelectric impulse, and the outputting piezoelectric signal contains the
      urea/uric-acid concentration information in body fluids. This piezoelectric
      biosensing process does not need an external electricity supply or battery. The e
      skin was implanted under the abdominal skin of a mouse and provided in situ
      analysis of the kidney-disease parameters. These results provide a new approach
      for developing a self-powered in situ body fluids-analysis technique for chronic
      disease diagnosis.

PMID- 29323396
TI  - Using DNA strand displacement to control interactions in DNA-grafted colloids.
AB  - Grafting DNA oligonucleotides to colloidal particles leads to specific,
      reversible interactions between those particles. However, the interaction
      strength varies steeply and monotonically with temperature, hindering the use of
      DNA-mediated interactions in self-assembly. We show how the dependence on
      temperature can be modified in a controlled way by incorporating DNA strand
      displacement reactions. The method allows us to make multicomponent systems that
      can self-assemble over a wide range of temperatures, invert the dependence on
      temperature to design colloidal systems that melt upon cooling, controllably
      transition between structures with different compositions, or design systems with
      multiple melting transitions. This wide range of behaviors can be realized simply
      by adding a small number of DNA strands to the solution, making the approach
      modular and straightforward to implement. We conclude with practical
      considerations for designing systems of DNA-mediated colloidal interactions.

PMID- 29323397
TI  - Spontaneous symmetry breaking of charge-regulated surfaces.
AB  - The interaction between two chemically identical charge-regulated surfaces is
      studied using the classical density functional theory. In contrast to common
      expectations and assumptions, under certain realistic conditions we find a
      spontaneous emergence of disparate charge densities on the two surfaces. The
      surface charge densities can differ not only in their magnitude, but quite
      unexpectedly, even in their sign, implying that the electrostatic interaction
      between the two chemically identical surfaces can be attractive instead of
      repulsive. Moreover, an initial symmetry with equal charge densities on both
      surfaces can also be broken spontaneously upon decreasing the separation between
      the two surfaces. The origin of this phenomenon is a competition between the
      adsorption of ions from the solution to the surface and the interaction between
      the adsorbed ions already on the surface. These findings are fundamental for the
      understanding of the forces between colloidal objects and, in particular, they
      are bound to strongly influence the present picture of protein interaction.

PMID- 29323398
TI  - Night-shift work and hematological cancers: a population based case-control study
      in three Nordic countries.
AB  - Objective The aim of this case-control study was to assess the effect of night
      shift work on the risk of hematological cancers. Methods The study included 39
      371 leukemia, 56 713 non-Hodgkin lymphoma, 9322 Hodgkin lymphoma, and 26 188
      multiple myeloma cases diagnosed between 1961 and 2005 in Finland, Sweden, and
      Iceland. Five controls for each case were selected from the Nordic Occupational
      Cancer Study (NOCCA) cohort, matched by year of birth, sex and country. Night
      shift exposure was assessed by using the NOCCA job-exposure matrix (JEM). Odds
      ratios (OR) and 95% confidence intervals (95% CI) were calculated from
      conditional logistic regression models. Results Overall, night work was not
      associated with a risk of hematological cancers. We observed a small but non
      significantly increased risk for leukemia (OR 1.07, 95% CI 0.99-1.16), especially
      for acute myeloid leukemia (OR 1.15, 95% CI 0.97-1.36) among workers exposed to a
      high level of cumulative night work exposure. Night work exposure was not
      associated with lymphatic cancers and multiple myeloma. Conclusion This study did
      not support associations between night-shift work and hematological cancers.

PMID- 29323399
TI  - [Usability and acceptability of portable exoskeletons for gait training in
      subjects with spinal cord injury: a systematic review].
AB  - INTRODUCTION: Spinal cord injury limits severely life expectancy and it causes in
      a restriction in the activities of the daily life of the subjects who suffer it.
      Training the gait with portable exoskeletons in subjects with spinal cord injury
      is a new approach to rehabilitation. AIM: To examine the usability and
      acceptability of these devices for gait training in subjects with spinal cord
      injury. PATIENTS AND METHODS: A literature search was conducted until February
      2017 in the databases: Medline (PubMed, EBSCO), PEDro, Scopus and Web of Science.
      The methodological quality, the level of scientific evidence and the strength of
      recommendation were evaluated. RESULTS: Finally, eight studies were considered
      recruiting a total of 45 patients. The training programs had an average of 35
      sessions and a duration 60 minutes approximately. In general, no adverse events
      and no relevant increases in pain, blood pressure, heart rate or fatigue were
      reported. In addition, the satisfaction with the intervention and the perception
      of quality of life of the participants were quite high. CONCLUSIONS: The
      rehabilitation of the gait with portable exoskeletons seems to be a safe
      intervention that generates acceptance and satisfaction among patients with
      spinal cord injury.

PMID- 29323400
TI  - [Amimia in Parkinson's disease. Significance and correlation with the clinical
      features].
AB  - INTRODUCTION: Reduced facial expression or amimia is one of the most typical
      characteristics of Parkinson's disease (PD). Despite being described in classic
      texts, its significance, physiopathology and correlation with motor and non-motor
      symptoms is largely unknown. PATIENTS AND METHODS: We have studied facial
      bradykinesia in a group of 84 de novo PD patients prospectively evaluated for
      five years. We also studied the relationship of facial bradykinesia with
      depression in a subgroup of 30 patients. RESULTS: Baseline and follow-up
      assessments were performed with the Unified Parkinson's Disease Rating Scale
      (UPDRS). Baseline facial bradykinesia was rated according to item 19 of UPDRS.
      Baseline facial bradykinesia correlated with total and motor baseline UPDRS. In
      addition, baseline bradykinesia correlated with total and motor UPDRS at five
      years. However baseline bradykinesia did not influence the presence of motor
      (motor fluctuation, dyskinesias and freezing of gait) or non-motor complications
      (delusion, behavior abnormalities and dementia) at five years. Finally a subgroup
      of 30 patients completed the self-report version of the Quick Inventory of
      Depressive Symptoms (QIDS-SR16) questionnaire, facial bradykinesia did not
      correlate with QIDS-SR16 scores. CONCLUSION: Our study suggests that baseline
      facial bradykinesia correlates with general baseline situation in PD and even
      might predict the motor and functional status at five years.

PMID- 29323401
TI  - [Efficacy of interventions with video games consoles in stroke patients: a
      systematic review].
AB  - INTRODUCTION: In recent years video games and games consoles have been developed
      that are potentially useful in rehabilitation, which has led to studies conducted
      to evaluate the degree of efficacy of these treatments for people following a
      stroke. AIM: To analyse the literature available related to the effectiveness of
      applying video games consoles in the functional recovery of the upper extremities
      in subjects who have survived a stroke. PATIENTS AND METHODS: A review of the
      literature was conducted in the CINHAL, Medline, PEDro, PsycArticles, PsycInfo,
      Science Direct, Scopus and Web of Science databases, using the query terms 'video
      game', 'stroke', 'hemiplegia', 'upper extremity' and 'hemiparesis'. After
      applying the eligibility criteria (clinical trials published between 2007 and
      2017, whose participants were adults who had suffered a stroke with involvement
      of the upper extremity and who used video games), the scientific quality of the
      selected studies was rated by means of the PEDro scale. Eleven valid clinical
      trials were obtained for the systematic review. RESULTS: The studies that were
      selected, all of which were quantitative, presented different data and the
      inferential results indicated different levels of significance between control
      and experimental groups (82%) or between the different types of treatment (18%).
      CONCLUSIONS: The use of video games consoles is a useful complement for the
      conventional rehabilitation of the upper extremities of persons who have survived
      a stroke, since it increases rehabilitation time and enhances the recovery of
      motor functioning. Nevertheless, homogeneous intervention protocols need to be
      implemented in order to standardise the intervention.

PMID- 29323402
TI  - Neurogenic stuttering: a review of the literature.
AB  - INTRODUCTION: Neurogenic stuttering is a disorder of neurologic origin in the
      rhythm of speech during which the patient knows exactly what he wants to say but
      is unable to because of an involuntary prolongation, cessation or repetition of a
      sound. AIM: To assemble new insights regarding the epidemiology, pathophysiology,
      diagnosis, evaluation and treatment of neurogenic stuttering. DEVELOPMENT: A
      review of all PubMed and Scopus published articles between January 2000 and
      September 2016 was performed. Thirty-three publications were analyzed. Neurogenic
      stuttering is a rare entity whose epidemiological incidence is yet not fully
      established. It is correlated with several neurological diseases and with several
      possible localizations within the nervous system. Notwithstanding the recent
      advances in the understanding of the underlying mechanism, it is not yet possible
      to establish a single pathophysiological mechanism of neurogenic stuttering. The
      differential diagnosis is complex and requires the detailed knowledge of other
      language disorders. The treatment is currently based on specific speech language
      therapy strategies. CONCLUSION: Neurogenic stuttering is a complex disorder which
      is not fully understood. Additional studies might help to better explain the
      underlying pathophysiological mechanism and to open doors to novel therapeutic
      methods.

PMID- 29323403
TI  - [Ultrasound study of the vagal nerve as a diagnostic tool in Guillain-Barre
      syndrome].

PMID- 29323404
TI  - [Occipital intermittent rhythmic delta activity as the interictal pattern in an
      adult with focal epilepsy].

PMID- 29323405
TI  - [The challenges of a re-emerging disease: tuberculous meningo-encephalitis].

PMID- 29323406
TI  - Type and timing of dietary acid intake and tooth wear among American adults.
AB  - OBJECTIVES: To explore the interrelationship between type and timing of dietary
      acid intake and tooth wear among American adults. METHODS: This study used data
      from 3,586 adults, aged 18 years and older, who participated in the National
      Health and Nutrition Examination Survey (NHANES) 2003-04. Information on four
      types of acidic food and beverages (fruits, fruit juices, alcoholic drinks, and
      soft drinks) and timing of consumption (meals versus snacks, defined according to
      percentage of total energy intake, self-reported eating occasion, and time of
      day) was extracted from two 24-hour dietary recalls. The association of the type
      and timing of dietary acid intake with the number of surfaces with moderate-to
      severe tooth wear was assessed in Hurdle models to account for the excess zero
      counts and over-dispersion. Models were adjusted for socio-demographic factors,
      acid reflux medication, and dental insurance coverage. RESULTS: The daily intake
      of soft drinks was associated with tooth wear, while those of fruits, fruit
      juices, and alcoholic drinks were not. The consumption of soft drinks with meals
      was the only factor consistently associated with tooth wear, irrespective of the
      method used to define meals versus snacks. The above associations were found with
      the number of surfaces with tooth wear (among those with the condition), but not
      with the odds of having tooth wear (among all participants). CONCLUSION: The
      consumption of soft drinks with meals was associated with moderate-to-severe
      tooth wear among American adults. Other acidic foods and beverages were not
      associated with tooth wear, regardless of their timing of consumption.

PMID- 29323407
TI  - Behind the lines: Toward an aesthetic framework for psychoanalytic psychotherapy.
AB  - This article describes the author's development of an aesthetic approach to
      psychoanalytic psychotherapy of patients suffering from traumatic levels of grief
      by describing her experiences as a patient, a therapist, and a consultant to the
      design firm that partnered with the National September 11 Memorial and Museum.
      Using Aristotle's On Poetics as an inspiration, this article explores the ways
      dialogical storytelling creates a therapeutic "action-plot" that transforms
      reversals of fortune. Attending to patients' first-person phenomenological
      experience (without attributing cause), therapists help them transform their
      losses by listening to their stories. Therapists dwell with them in uncertainties
      while marking time in regularly scheduled meetings; they accompany their patients
      on a journey while also orienting to their modes of travel. They simultaneously
      co-construct tales of the journey, attentive to the poetic dimensions of sight,
      sound, and space that they encounter. In so doing, therapists serve not just
      guides and judges, but artists, bringing meanings to the trail.

PMID- 29323408
TI  - Prediction analysis and quality assessment of microwell array images.
AB  - Microwell arrays are widely used for the analysis of fluorescent-labelled
      biomaterials. For rapid detection and automated analysis of microwell arrays, the
      computational image analysis is required. Support Vector Machines (SVM) can be
      used for this task. Here, we present a SVM-based approach for the analysis of
      microwell arrays consisting of three distinct steps: labeling, training for
      feature selection, and classification into three classes. The three classes are
      filled, partially filled, and unfilled microwells. Next, the partially filled
      wells are analyzed by SVM and their tendency towards filled or unfilled tested
      through applying a Gaussian filter. Through this, all microwells can be
      categorized as either filled or unfilled by our algorithm. Therefore, this SVM
      based computational image analysis allows for an accurate and simple
      classification of microwell arrays.

PMID- 29323409
TI  - In Vitro Comparison of Two Neonatal ECMO Circuits Using a Roller or Centrifugal
      Pump With Three Different In-Line Hemoconcentrators for Maintaining Hemodynamic
      Energy Delivery to the Patient.
AB  - The objective of this study was to compare three different hemoconcentrators
      (Hemocor HPH 400, Mini, and Junior) with two different neonatal ECMO circuits
      using a roller or a centrifugal pump at different pseudo-patient pressures and
      flow rates in terms of hemodynamic properties. This evidence-based research is
      necessary to optimize the ECMO circuitry for neonates. The circuits used a 300-mL
      soft-shell reservoir as a pseudo-patient approximating the blood volume of a 3 kg
      neonate, two blood pumps, and a Quadrox-iD Pediatric oxygenator with three
      different in-line hemoconcentrators (Hemocor HPH 400, Mini, and Junior). One
      circuit used a Maquet H20 roller pump and another circuit used a Maquet RotaFlow
      centrifugal pump. The circuit was primed with lactated Ringer's solution followed
      by heparinized packed red blood cells with a hematocrit of 40%. The pseudo
      patient's pressure was manually maintained at 40, 60, or 80 mm Hg and the flow
      rate was maintained at 200, 400, or 600 mL/min with a circuit temperature of 36
      degrees C. Pressure and flow data was recorded using a custom-made data
      acquisition device. Mean pressures, diverted blood flow, pressure drops, and
      total hemodynamic energy (THE) were calculated for each experimental condition.
      The roller pump and centrifugal pump performed similarly for all hemodynamic
      properties with all experimental conditions. The Hemocor HPH Junior
      hemoconcentrator added the highest resistance to the circuit. The Hemocor HPH
      Junior provided the highest circuit pressures, lowest diverted blood flow,
      highest pressure drop across the circuit, and highest THE generated by the pump.
      The Hemocor HPH 400 added the least resistance to the circuit, providing the
      lowest circuit pressures, more diverted flow, lowest pressure drop, and the
      lowest THE generated by the pump. However, the THE delivered to the patient was
      the same for the three hemoconcentrators. While the three hemoconcentrators
      performed differently in terms of hemodynamic properties throughout the circuit,
      the THE transmitted to the patient was similar for all three hemoconcentrators
      due to the consistent pseudo-patient's pressure that was manually maintained for
      each trial. While the THE delivered to the patient indicates similar perfusion
      for these patients with any of the three hemoconcentrators, the differences in
      added resistance to the circuit may impact the decision of which hemoconcentrator
      is used. There was no clinically significant difference between the two circuits
      with the roller versus centrifugal pump in terms of hemodynamic properties in
      this study. Further in vivo research is warranted to confirm our findings.

PMID- 29323410
TI  - Housing First and Photovoice: Transforming Lives, Communities, and Systems.
AB  - This article presents findings from a community-based participatory evaluation of
      a Housing First program on the Island of O'ahu. In this study, clients in a
      Housing First program used Photovoice to evaluate the program and to advocate for
      progressive housing policies. Written together by members of the Housing First
      Photovoice group, this collaborative article describes the outcomes from both the
      Housing First program and the Photovoice project and demonstrates the ways in
      which participatory program evaluations can interact with client-driven programs
      like Housing First to produce a cumulative, transformative impact. Findings
      suggest that community psychologists hoping to re-engage with community mental
      health systems through enacting transformative change should consider taking a
      community-based participatory approach to program evaluation because increased
      client voice in community mental health programs and their evaluations can have
      far-reaching, transformative impacts for research, practice, and policy.

PMID- 29323411
TI  - Demographic quantification of carbon and nitrogen dynamics associated with root
      turnover in white clover.
AB  - As well as capturing resources, roots lose resources during their lives. We
      quantified carbon (C) and nitrogen (N) losses associated with root turnover in
      white clover (Trifolium repens L.). We grew contrasting cultivars for 18 weeks in
      soil microcosms. Using repeated in situ observations, destructive sampling, and
      demographic analysis, we measured changes in C and N concentrations in dry matter
      of 1st- or 2nd-order (terminal) roots to derive C and N fluxes into and out of
      root cohorts. C and N fluxes from roots during turnover depended on cohort age
      and order. Ninety per cent of losses occurred from 2nd-order cohorts younger than
      18 weeks. Losses were greater from roots of the larger, faster growing cultivar
      Alice than from the smaller lower yielding cultivar S184. C:N ratios of roots and
      lost material were similar within each order and between cultivars but smaller in
      2nd- compared with 1st-order roots. C and N losses during root turnover could be
      equivalent to at least 6% of aboveground dry matter production in S184 and 12% in
      Alice at the field scale. C and N losses associated with root turnover will have
      potentially significant and previously unrecognized impacts on crop productivity,
      resource dynamics, and long-term soil fertility.

PMID- 29323412
TI  - Microsystems of Recovery in Homeless Services: The Influence of Service Provider
      Values on Service Users' Recovery Experiences.
AB  - There is still much to learn about how aspects of the ecology of homelessness
      shape homeless adults' recovery experiences. In the present mixed-methods study,
      the relationship of service providers' work-related values to their service
      users' recovery experiences in the microsystem of homelessness were examined.
      Service providers completed semi-structured qualitative interviews about their
      service users, daily work activities, and work-related goals. At three time
      points, their service users completed quantitative measures of choice, mastery,
      and recovery in four life domains: physical health, psychiatric symptoms,
      substance use, and community integration. Service providers' interview
      transcripts were coded for three indicators of values: assumptions, actions, and
      end-states. Summative Content Analysis was used to transform qualitative codes
      into numeric data so they could be used to predict service users' recovery. In a
      series of growth curve models, the extent to which service providers' end-state
      values, as an indicator of consumer-led values, was shown to indirectly predict
      service users' recovery experiences, through their perceived choice and mastery.
      Findings confirm that providers' values are an important influence on service
      users' recovery. Results are discussed in terms of their implications for
      recovery-oriented theory and practice.

PMID- 29323413
TI  - Extracorporeal Membrane Oxygenation for Refractory Severe Respiratory Failure in
      Acute Interstitial Pneumonia.
AB  - Acute interstitial pneumonia (AIP) is a rare idiopathic interstitial lung disease
      with rapid progressive respiratory failure and high mortality. In the present
      report, three cases of AIP complicated by refractory respiratory failure
      supported with extracorporeal membrane oxygenation (ECMO) are presented. One male
      and two female patients (ages 27-59) were included. Venovenous ECMO support was
      provided using miniaturized systems, with two-site femoro-jugular circuit
      configuration. Despite lung protective ventilation, prone position and
      neuromuscular blockade, refractory respiratory failure of unknown etiology
      supervened (ratio of arterial oxygen partial pressure to fractional inspired
      oxygen 46-130) and ECMO was initiated after 3-7 days of mechanical ventilation.
      AIP diagnosis was established after exclusion of infectious and noninfectious
      acute respiratory distress syndrome on the basis of clinical and analytical data,
      bronchoalveolar lavage analysis and lung imaging, with a confirmatory surgical
      lung biopsy revealing diffuse alveolar damage of unknown etiology.
      Immunosuppressive treatment consisted in high-dose corticosteroids and
      cyclophosphamide in one case. Two patients survived to hospital discharge. ECMO
      allowed AIP diagnosis and treatment in the presence of refractory respiratory
      failure, therefore reducing ventilator-induced lung injury and bridging lung
      recovery in two patients. ECMO referral should be considered in refractory
      respiratory failure if AIP is suspected.

PMID- 29323414
TI  - On the solution multiplicity of the Fleishman method and its impact in simulation
      studies.
AB  - The Fleishman third-order polynomial algorithm is one of the most-often used non
      normal data-generating methods in Monte Carlo simulations. At the crux of the
      Fleishman method is the solution of a non-linear system of equations needed to
      obtain the constants to transform data from normality to non-normality. A rarely
      acknowledged fact in the literature is that the solution to this system is not
      unique, and it is currently unknown what influence the different types of
      solutions have on the computer-generated data. To address this issue, analytical
      and empirical investigations were conducted, aimed at documenting the impact that
      each solution type has on the design of computer simulations. In the first study,
      it was found that certain types of solutions generate data with different
      multivariate properties and wider coverage of the theoretical range spanned by
      population correlations. In the second study, it was found that previously
      published recommendations from Monte Carlo simulations could change if different
      types of solutions were used to generate the data. A mathematical description of
      the multiple solutions to the Fleishman polynomials is provided, as well as
      recommendations for users of this method.

PMID- 29323415
TI  - Selecting polychoric instrumental variables in confirmatory factor analysis: An
      alternative specification test and effects of instrumental variables.
AB  - The polychoric instrumental variable (PIV) approach is a recently proposed method
      to fit a confirmatory factor analysis model with ordinal data. In this paper, we
      first examine the small-sample properties of the specification tests for testing
      the validity of instrumental variables (IVs). Second, we investigate the effects
      of using different numbers of IVs. Our results show that specification tests
      derived for continuous data are extremely oversized at all sample sizes when
      applied to ordinal variables. Possible modifications for ordinal data are
      proposed in the present study. Simulation results show that the modified
      specification tests with all available IVs are able to detect model
      misspecification. In terms of estimation accuracy, the PIV approach where the IVs
      outnumber the endogenous variables by one produces a lower bias but a higher
      variation than the PIV approach with more IVs for correctly specified factor
      loadings at small samples.

PMID- 29323416
TI  - Citizenship and Community Mental Health Care.
AB  - Citizenship is an approach to supporting the social inclusion and participation
      in society of people with mental illnesses. It is receiving greater attention in
      community mental health discourse and literature in parallel with increased
      awareness of social determinants of health and concern over the continued
      marginalization of persons with mental illness in the United States. In this
      article, we review the definition and principles of our citizenship framework
      with attention to social participation and access to resources as well as rights
      and responsibilities that society confers on its members. We then discuss our
      citizenship research at both individual and social-environmental levels,
      including previous, current, and planned efforts. We also discuss the role of
      community psychology and psychologists in advancing citizenship and other themes
      relevant to a citizenship perspective on mental health care and persons with
      mental illness.

PMID- 29323418
TI  - Synthesis of 2-d-acrylamide.
AB  - 2-d-Acrylamide was synthesized via the 2-step procedure starting from
      acrylonitrile and deuterium oxide. This procedure affords 2-d-acrylamide in 99.9%
      chemical purity and 98.4% isotopic enrichment.

PMID- 29323417
TI  - Loss of Ethanol Inhibition of N-Methyl-D-Aspartate Receptor-Mediated Currents and
      Plasticity of Cerebellar Synapses in Mice Expressing the GluN1(F639A) Subunit.
AB  - BACKGROUND: Glutamatergic N-methyl-d-aspartate receptors (NMDARs) are well known
      for their sensitivity to ethanol (EtOH) inhibition. However, the specific manner
      in which EtOH inhibits channel activity and how such inhibition affects
      neurotransmission, and ultimately behavior, remains unclear. Replacement of
      phenylalanine 639 with alanine (F639A) in the GluN1 subunit reduces EtOH
      inhibition of recombinant NMDARs. Mice expressing this subunit show reduced EtOH
      induced anxiolysis, blunted locomotor stimulation following low-dose EtOH
      administration, and faster recovery of motor function after moderate doses of
      EtOH, suggesting that cerebellar dysfunction may contribute to some of these
      behaviors. In the mature mouse cerebellum, NMDARs at the cerebellar climbing
      fiber (CF) to Purkinje cell (PC) synapse are inhibited by low concentrations of
      EtOH and the long-term depression (LTD) of parallel fiber (PF)-mediated currents
      induced by concurrent activation of PFs and CFs (PF-LTD) requires activation of
      EtOH-sensitive NMDARs. In this study, we examined cerebellar NMDA responses and
      NMDA-mediated synaptic plasticity in wild-type (WT) and GluN1(F639A) mice.
      METHODS: Patch-clamp electrophysiological recordings were performed in acute
      cerebellar slices from adult WT and GluN1(F639A) mice. NMDAR-mediated currents at
      the CF-PC synapse and NMDAR-dependent PF-LTD induction were compared for genotype
      dependent differences. RESULTS: Stimulation of CFs evoked robust NMDA-mediated
      excitatory postsynaptic currents (EPSCs) in PCs that were similar in amplitude
      and kinetics between WT and GluN1(F639A) mice. NMDA-mediated CF-PC EPSCs in WT
      mice were significantly inhibited by EtOH (50 mM) while those in mutant mice were
      unaffected. Concurrent stimulation of CF and PF inputs induced synaptic
      depression of PF-PC EPSCs in both WT and mutant mice, and this depression was
      blocked by the NMDA antagonist DL-APV. The synaptic depression of PF-PC EPSCs in
      WT mice was also blocked by a low concentration of EtOH (10 mM) that had no
      effect on plasticity in GluN1(F639A) mice. CONCLUSIONS: These results demonstrate
      that inhibition of cerebellar NMDARs may be a key mechanism by which EtOH affects
      cerebellar-dependent behaviors.

PMID- 29323419
TI  - Evaluation of viral contamination in a baculovirus expression system.
AB  - Insect expression systems based on baculovirus are widely used for generating
      recombinant proteins. Here, the infectivity of baculoviruses under the
      physiological stresses of 'freeze-thaw' and sonication and the baculoviral
      contamination of recombinant proteins after protein purification were evaluated.
      Our findings suggest that Nonidet P-40 (NP-40) treatment of baculoviruses
      completely abolishes their infectivity and that recombinant proteins purified
      with affinity beads do not include infectious baculoviruses. We therefore suggest
      that baculovirus is completely inactivated by NP-40 treatment and that
      recombinant proteins are unlikely to be contaminated with infectious
      baculoviruses after their affinity purification.

PMID- 29323420
TI  - On the influence of lipid-induced optical anisotropy for the bioimaging of exo-
      or endocytosis with interference microscopic imaging.
AB  - Some implementations of interference microscopy imaging use digital holographic
      measurements of complex scattered fields to reconstruct three-dimensional
      refractive index maps of weakly scattering, semi-transparent objects, frequently
      encountered in biological investigations. Reconstruction occurs through
      application of the object scattering potential which assumes an isotropic
      refractive index throughout the object. Here, we demonstrate that this assumption
      can in some circumstances be invalid for biological imaging due to the presence
      of lipid-induced optical anisotropy. We show that the nanoscale organization of
      lipids in the observation of cellular endocytosis with polarized light induces a
      significant change in far-field scattering. We obtain this result by presenting a
      general solution to Maxwell's equations describing light scattering of core-shell
      particles near an isotropic substrate covered with an anisotropic thin film. This
      solution is based on an extension of the Bobbert-Vlieger solution for particle
      scattering near a substrate delivering an exact solution to the scattering
      problem in the near field as well as far field. By applying this solution to
      study light scattering by a lipid vesicle near a lipid bilayer, whereby the
      lipids are represented through a biaxial optical model, we conclude through
      ellipsometry concepts that effective amounts of lipid-induced optical anisotropy
      significantly alter far-field optical scattering in respect to an equivalent
      optical model that neglects the presence of optical anisotropy.

PMID- 29323421
TI  - Head and Neck Cancer Tumor Seeding at the Percutaneous Endoscopic Gastrostomy
      Site.
AB  - The National Institutes of Health National Cancer Institute estimates that over
      13,000 new cases of head and neck cancer (HNC) will be diagnosed in 2017.
      Patients with HNC often require enteral nutrition (EN) via gastrostomy tube to
      provide nutrition support and hydration because of tumor obstruction of the
      oropharynx and/or cumulative effects of chemoradiation therapy. The percutaneous
      endoscopic gastrostomy (PEG) tube has become the preferred technique for EN
      access because placement is considered a minimally invasive procedure. There are
      3 methods of PEG placement: Gauderer-Ponsky "pull," Sachs-Vine "push," and
      Russell "push" method. The Gauderer-Ponsky "pull" method has become the preferred
      method of PEG placement. It has been previously reported that the rate of stomal
      metastasis can be 0.5%-1% of those undergone the Gauderer-Ponsky "pull" method
      that is consistent with HNC morphology. Other researchers believe the rate may be
      as high as 0.5%-3%. This article reviews the 3 methods of PEG placement, as well
      as all potential complications, including metastatic seeding at the PEG site. In
      addition, 1 additional case of tumor seeding at the PEG site will be reviewed.
      Consideration for avoidance of the Gauderer-Ponsky pull method of PEG placement
      or other methods of feeding tube placement where the gastrostomy tube has to pass
      through the oral cavity before exiting the abdominal wall in patients with
      squamous cell carcinoma of the head and neck should be considered.

PMID- 29323422
TI  - Community interest and feasibility of using a novel smartphone-based formaldehyde
      exposure detection technology.
AB  - OBJECTIVE: This study is the first community engagement phase of a project to
      develop a residential formaldehyde detection system. The objectives were to
      conduct a feasibility assessment for device use, and identify factors associated
      with concerns about environmental exposure and community interest in this device.
      DESIGN AND SAMPLE: A cross-sectional, internet-based survey employing community
      based participatory research principles was utilized. 147 individuals
      participated from a focused Waycross, Georgia (58.5%) and broader national sample
      (41.5%). MEASURES: Variables included acceptable cost and number of testing
      samples, interest in conducting tests, levels of concern over pollutants, health
      status, housing, and demographics. RESULTS: The majority of participants desired
      a system with fewer than 10 samples at <=$15.00 per sample. Statistically
      significant higher levels of concern over air quality, formaldehyde exposure, and
      interest in testing formaldehyde were observed for those with overall worse
      health status and living in the Waycross, Georgia geographic region. Significant
      differences in formaldehyde testing interest were observed by health status (OR =
      0.31, 95% CI = 0.12-0.81 for home testing) and geographic location (OR = 3.16,
      95% CI = 1.22-8.14 for home and OR = 4.06, 95% CI = 1.48-11.12 for ambient
      testing) in multivariate models. CONCLUSIONS: Geographic location and poorer
      general health status were associated with concerns over and interest in
      formaldehyde testing.

PMID- 29323423
TI  - Enteral Feeding Tube Clogging: What Are the Causes and What Are the Answers? A
      Bench Top Analysis.
AB  - BACKGROUND: Clogged enteral feeding tubes remain a significant barrier to the
      delivery of nutrition, hydration, and medications to patients who cannot tolerate
      oral intake. There is limited research that compares the relative efficacy of
      different methods used to clear a clogged feeding tube. The objectives of this
      study were to better understand the factors that contribute to enteral feeding
      tube clogging and to test the efficacy of 3 methods for clearing clogged feeding
      tubes. METHODS: Three formulations of clogs were artificially created and tested
      in vitro and composed of various quantities of crushed medication (ie, aspirin)
      and 0.15 g coagulated protein (ie, tofu). The following 3 clog clearing
      strategies were tested on all clog types (n = 5 clogs/formulation/treatment):
      warm water flushes, an enzyme treatment, and an actuated mechanical occlusion
      clearing device. RESULTS: The variable among the clog types that appears most
      responsible for decreased clearing success is the state of the coagulated
      protein. Dried-out protein appears to makes a greater difference than increasing
      the medication quantity. The actuated mechanical occlusion clearing device was
      significantly more successful (93%) when compared with warm water flushes (20%)
      and the commercially available enzyme treatment (33%; P < .005) at clearing the
      clogs. The actuated device required significantly less total procedure time (P <
      .005) and total nursing time (P < .005) when compared with the other 2 clearing
      methods. CONCLUSIONS: When clogs occur, they can be quickly and effectively
      resolved by the actuated device, but other methodologies such as water and enzyme
      treatments may be of assistance.

PMID- 29323424
TI  - In vitro and in vivo effects of ophthalmic solutions on silicone hydrogel bandage
      lens material Senofilcon A.
AB  - BACKGROUND: Acuvue Oasys silicone hydrogel contact lenses (Senofilcon A) are used
      as bandage lenses and often combined with ophthalmic solutions in the treatment
      of ocular diseases. Concerns have been raised regarding the compatibility and
      effect of eye-drop solutions on the bandage lenses, which have led to frequent
      replacement of lenses causing clinical problems. Some patients experience pain or
      discomfort during treatments and the accumulation of drugs and preservatives in
      lenses has been suggested as a possible reason. The aim with this study was to
      investigate the effect of ophthalmic solutions on silicone hydrogel bandage lens
      material Senofilcon A in vitro and in vivo. METHODS: The effect of three common
      ophthalmic solutions Isopto-Maxidex, Timosan and Oftaquix on Acuvue Oasys
      (Senofilcon A) bandage lenses was evaluated. An in vitro model method was
      developed where drug and preservative uptake by Acuvue Oasys was monitored with
      ultraviolet-visible spectroscopy and laser desorption ionisation mass
      spectrometry. Surface morphology changes of the lenses were evaluated using
      scanning electron microscopy. The method was then implemented for the in vivo
      pilot study evaluating lenses worn by patients. RESULTS: In vitro model study
      monitoring the drug and preservatives uptake showed that the active ingredients
      from all the eye drops together with preservatives were taken up by the lenses in
      significant amounts. For the in vivo study no traces of active ingredients or
      preservatives could be found on the worn and treated lenses regardless of time
      being worn or dosage profiles. The surface morphology changes in the in vivo
      study were also minor in contrast to the changes observed in the in vitro
      scanning electron microscopy images. CONCLUSION: The in vivo results demonstrate
      minor effects of the ophthalmic solutions on the worn lenses. These results do
      not support the building up of preservatives and drugs on the contact lenses as
      the cause of pain or discomfort experienced by some patients, which is
      encouraging for the use of bandage lenses in combination with ophthalmic
      solutions.

PMID- 29323425
TI  - Evaluating Mid-Upper Arm Circumference Z-Score as a Determinant of Nutrition
      Status.
AB  - BACKGROUND: Mid-upper arm circumference (MUAC) z-score, has recently been listed
      as an independent indicator for pediatric malnutrition. This investigation
      examined the relationship between MUAC z-score and the z-scores for conventional
      indicators (ie, weight-for-length and body mass index) to expand the available
      evidence for nutrition classification z-score threshold ranges in U.S. practice
      settings. METHODS: This was a single-center study of children through 18 years of
      age seen between October 2015 and September 2016. Height and weight were obtained
      on intake. MUAC was measured at midpoint of the humerus, between the acromion and
      olecranon. Age-specific and gender-specific z-score values were calculated using
      published lambda, MU, and sigma values derived from Centers for Disease Control
      and Prevention reference data. Nutrition status was determined from biochemical
      data; prior history; anthropometrics; weight gain velocity; weight loss, if
      present; and nutrient intake. RESULTS: 5,004 children (7.5 +/- 5.7 years, 53%
      boys) were evaluated. As expected, MUAC z-scores were significantly correlated
      with body mass index (r = 0.789, P < .01) and weight-for-length (r = 0.638, P <
      .01) z-scores. There was a large degree of overlap in z-scores for all indicators
      between nutrition status groups; however, MUAC z-scores spanned a narrower range
      of values such that mean MUAC z-scores are lower in children classified as
      overweight/obese and higher in children who were severely malnourished than the
      corresponding body mass index or weight-for-length z-scores. CONCLUSION: These
      data are the first to suggest that the z-score ranges used to define various
      stages of malnutrition may not be the same for all indicators.

PMID- 29323426
TI  - Vision in children with autism spectrum disorder: a critical review.
AB  - Autism spectrum disorder (ASD) is a common neurodevelopmental condition with
      approximately 1-2 per cent prevalence in the population. The condition has
      lifelong effects for the individual and family, and early intervention and
      management helps maximise quality of life and outcomes. Many studies of vision in
      ASD have attempted to link the behavioural and sensory deficits in ASD with
      underlying visual processing. From this work, it is clear that individuals with
      ASD 'see' and process the world differently, but there remain gaps in our
      understanding. This review will summarise our current knowledge of key aspects of
      visual functions and the optometric profile of ASD. This includes findings
      regarding visual acuity and contrast sensitivity, refractive error, eye
      movements, binocular vision, near visual functions and retinal structure in ASD.
      From this, a pattern of knowledge emerges for children with ASD: we should expect
      normal visual acuity; there will likely be atypical eye movements and
      susceptibility for subtle visuo-motor deficits, there is an increased prevalence
      of strabismus; an increased likelihood of astigmatism and possibly other
      refractive errors; attention, crowding and task complexity will likely be
      problematic; and retinal structure and function may be compromised. Bringing this
      together, these findings highlight that further work is necessary, not only to
      understand how higher-level functions link to behaviours, but also to ensure
      there is a sound understanding of the building-blocks of vision to fully grasp
      the profile of visual processing as a whole in ASD. This review will give a
      translational viewpoint for clinicians, and underline the benefits of
      comprehensive vision care in ASD.

PMID- 29323427
TI  - Duration of androgen deprivation therapy and nadir of testosterone at 20 ng/dL
      predict testosterone recovery to supracastrate level in prostate cancer patients
      who received external beam radiotherapy.
AB  - OBJECTIVES: To determine the predictors of testosterone recovery after
      termination of androgen deprivation therapy in high/intermediate-risk prostate
      cancer patients receiving external beam radiation therapy with neoadjuvant and
      adjuvant androgen deprivation therapy. METHODS: A total of 82 patients who
      underwent external beam radiation therapy with androgen deprivation therapy for
      prostate cancer were retrospectively analyzed. Serum testosterone levels after
      androgen deprivation therapy terminations were studied. Cox proportional hazard
      models and the Kaplan-Meier method were used for statistical analysis. RESULTS:
      Median age, baseline testosterone, nadir testosterone and duration of androgen
      deprivation therapy were 73 years, 456 ng/dL, 16 ng/dL and 26 months,
      respectively. Androgen deprivation therapy duration of 33 months (hazard ratio
      0.13; P = 0.0018), nadir testosterone of 20 ng/dL (hazard ratio 0.35; P = 0.0112)
      and testosterone >50 ng/dL at 6 months after androgen deprivation therapy
      termination (hazard ratio 0.21; P = 0.0075) were significantly associated with
      testosterone recovery to normal levels (200 ng/dL) on multivariate analysis.
      Androgen deprivation therapy duration of 33 months (hazard ratio 0.31; P =
      0.0023) and nadir testosterone of 20 ng/dL (hazard ratio 0.38; P = 0.0012) were
      significantly associated with testosterone recovery to the supracastrate level
      (50 ng/dL) on multivariate analysis. After dividing patients into three risk
      groups, the rate of testosterone recovery to the normal level after 2 years of
      androgen deprivation therapy termination was 100% in the low-risk group versus
      20.8% in the high-risk group (P < 0.0001); the rate of testosterone recovery to
      the supracastrate level was 100% in the low-risk group versus 51.5% in the high
      risk group (P < 0.0001). CONCLUSIONS: Duration of androgen deprivation therapy
      and achievement of nadir testosterone 20 ng/dL both predict testosterone recovery
      to the supracastrate level in prostate cancer patients undergoing external beam
      radiation therapy with androgen deprivation therapy.

PMID- 29323429
TI  - Editor's Note.

PMID- 29323428
TI  - Enteral Nutrition in the Management of Crohn's Disease: Reviewing Mechanisms of
      Actions and Highlighting Potential Venues for Enhancing the Efficacy.
AB  - Crohn's disease (CD) is a chronic condition that affects the gut and has adverse
      effects on growth and development. There is a global increase in the incidence
      and prevalence rates, and several factors are believed to contribute to this
      rise, including dietary habits. In contrast, the use of enteral nutrition (EN) as
      an exclusive source of nutrition is increasingly becoming the preferred induction
      treatment of pediatric CD patients in part to address the nutrition
      complications. However, EN therapy is considered less effective in adults with
      CD. A better understanding of the molecular mechanisms of enteral therapy will
      help improve the clinical management of CD. It is increasingly becoming evident
      that the therapeutic utility of EN is in part due to the reversal of the
      microbial changes and the direct immunomodulatory effects. Moreover, there is a
      potential tendency for enhancing the efficacy of EN therapy by improving the
      palatability of the given formulas and, more important, by magnifying the anti
      inflammatory properties. Recent observations have shown that the immunomodulatory
      effects of EN are mediated at least in part by blocking nuclear factor-kappaB.
      Furthermore, it is likely that several ingredients of EN contribute to this
      activity, in particular glutamine and arginine amino acids. In addition,
      manipulating the composition of EN therapy by altering concentrations of the key
      ingredients is found to have the potential for more efficient therapy. In this
      review, the underlying mechanisms of EN actions will be discussed further with a
      focus on the potential methods for enhancing the efficacy.

PMID- 29323430
TI  - Transsphincteric repair of rectourethral fistulas: 15 years of experience with
      the York Mason approach.
AB  - OBJECTIVES: To evaluate the surgical and functional outcomes of our single
      institution's 15-year experience with surgically treated rectourethral fistulas
      using a modification of the York Mason technique. METHODS: Prospectively recorded
      data between 2002 and 2016 of all patients who underwent transsphincteric repair
      of rectourethral fistula using a modified York Mason technique at Eskilstuna
      County Hospital, Eskilstuna, Sweden, were assessed. A total of 20 consecutive
      patients, including 17 referrals (85%) and three patients (15%) from our hospital
      have undergone the modified York Mason procedure. The surgical and functional
      outcomes were evaluated. RESULTS: Of the 20 patients, 18 were repaired
      successfully (90%), and one was combined with a dartos muscle interposition flap.
      No fistula recurrence occurred in the 18 successful repairs during the median
      follow-up time of 84.7 months. Before fistula repair, 12 patients (60%) underwent
      a diverting stoma. The remaining eight patients (40%) underwent repair and
      synchronous diverting stoma. We did not find any significant differences between
      patients in which the repair was successful compared with patients with failed
      repair, but diabetes, smoking and preoperative irradiation were much more
      frequent in the failed group. Of the 18 patients who had a successful repair, 17
      patients experienced normal voiding and no urinary incontinence. One patient was
      suffering from postprostatectomy incontinence before rectourethral fistula
      repair, and was successfully treated with Scott prosthesis. All the 13 patients
      in whom the stoma had been closed reported intact fecal continence and no anal
      stenosis postoperatively. CONCLUSIONS: The transsphincteric modified York Mason
      approach offers excellent exposure and a high fistula closure rate without fecal
      and urinary incontinence.

PMID- 29323431
TI  - Revisiting empirical rules for the determination of the absolute configuration of
      cascarosides and other (ox-)anthrones.
AB  - The introduction of the C10 -stereocenter of (ox-)anthrones by plant organisms is
      not stereospecific. Consequently, often, both (10S)- and (10R)-diastereomers can
      be found in the same plant. Motivated by the importance of a correct assignment
      of the configuration at C10 , this study revisits the nuclear magnetic resonance
      and electronic circular dichroism-based empirical rules for the determination of
      the absolute configuration by molecular dynamic simulations and electronic
      circular dichroism spectrum calculations. Furthermore, a vibrational circular
      dichroism spectroscopic characterization of these large and conformationally very
      flexible molecules reveals spectral signatures, which can be used to specifically
      distinguish the C10 stereochemistry. A detailed analysis of the underlying
      vibrational modes suggests that the observed spectral pattern of the investigated
      cascarosides may be generally characteristic for the C10 -stereocenter of (ox
      )anthrones and that they can be used for empirical spectra-structure
      correlations.

PMID- 29323432
TI  - Orthogonal 19 F-Labeling for Solid-State NMR Spectroscopy Reveals the
      Conformation and Orientation of Short Peptaibols in Membranes.
AB  - Peptaibols are promising drug candidates in view of their interference with
      cellular membranes. Knowledge of their lipid interactions and membrane-bound
      structure is needed to understand their activity and should be, in principle,
      accessible by solid-state NMR spectroscopy. However, their unusual amino acid
      composition and noncanonical conformations make it very challenging to find
      suitable labels for NMR spectroscopy. Particularly in the case of short
      sequences, new strategies are required to maximize the structural information
      that can be obtained from each label. Herein, l-3
      (trifluoromethyl)bicyclopent[1.1.1]-1-ylglycine, (R)- and (S)
      trifluoromethylalanine, and 15 N-backbone labels, each probing a different
      direction in the molecule, have been combined to elucidate the conformation and
      membrane alignment of harzianin HK-VI. For the short sequence of 11 amino acids,
      12 orientational constraints have been obtained by using 19 F and 15 N NMR
      spectroscopy. This strategy revealed a beta-bend ribbon structure, which becomes
      realigned in the membrane from a surface-parallel state towards a membrane
      spanning state, with increasing positive spontaneous curvature of the lipids.

PMID- 29323434
TI  - Thulium laser ablation facilitates retrograde intra-renal surgery for upper
      urinary tract urothelial carcinoma.

PMID- 29323433
TI  - Electrically Driven Microengineered Bioinspired Soft Robots.
AB  - To create life-like movements, living muscle actuator technologies have borrowed
      inspiration from biomimetic concepts in developing bioinspired robots. Here, the
      development of a bioinspired soft robotics system, with integrated self-actuating
      cardiac muscles on a hierarchically structured scaffold with flexible gold
      microelectrodes is reported. Inspired by the movement of living organisms, a
      batoid-fish-shaped substrate is designed and reported, which is composed of two
      micropatterned hydrogel layers. The first layer is a poly(ethylene glycol)
      hydrogel substrate, which provides a mechanically stable structure for the robot,
      followed by a layer of gelatin methacryloyl embedded with carbon nanotubes, which
      serves as a cell culture substrate, to create the actuation component for the
      soft body robot. In addition, flexible Au microelectrodes are embedded into the
      biomimetic scaffold, which not only enhance the mechanical integrity of the
      device, but also increase its electrical conductivity. After culturing and
      maturation of cardiomyocytes on the biomimetic scaffold, they show excellent
      myofiber organization and provide self-actuating motions aligned with the
      direction of the contractile force of the cells. The Au microelectrodes placed
      below the cell layer further provide localized electrical stimulation and control
      of the beating behavior of the bioinspired soft robot.

PMID- 29323435
TI  - Soluble CD14 levels in plasma and breastmilk of Malawian HIV+ women: Lack of
      association with morbidity and mortality in their exposed infants.
AB  - PROBLEM: Data on soluble CD14 (sCD14) during pregnancy and lactation are scarce.
      We assessed the levels of sCD14 in plasma and breastmilk of Malawian HIV-positive
      women and evaluated the possible association with morbidity and mortality in the
      HIV-exposed children. METHOD OF STUDY: One hundred and forty-nine mother/child
      pairs were studied. Women received antiretroviral therapy from 26 weeks of
      gestation to at least 6 months of exclusive breastfeeding. sCD14 concentrations
      were determined using an enzyme-linked immunosorbent assay. RESULTS: sCD14 levels
      measured at 26 weeks of pregnancy (median: 1418 ng/mL, IQR: 1086-1757) were
      inversely correlated to maternal CD4+ cell count (r = -.283, P = .001) and to
      neonatal birthweight (r = -.233, P = .008). At 6 months, sCD14 plasma levels were
      significantly higher compared to baseline (1993 ng/mL, IQR: 1482-2604, P < .001),
      and breastmilk sCD14 levels (7668 ng/mL, IQR: 5495-10207) were 4-fold higher than
      in plasma (although the concentrations in the two compartments were not
      correlated). No association was found between sCD14 levels in plasma or
      breastmilk and morbidity or mortality in children. CONCLUSION: Higher sCD14
      levels in HIV-positive women were associated with a more compromised maternal
      immunological status and to a lower neonatal birthweight, but not to poorer
      clinical outcomes in the HIV-exposed children.

PMID- 29323436
TI  - Molecular characterization and gene silencing of Laccase 1 in the grain aphid,
      Sitobion avenae.
AB  - Laccase 1 (Lac1), a polyphenol oxidase, has been proposed to be involved in
      insect iron metabolism and immunity responses. However, little information is
      available on the roles of Lac 1 in insect-plant interactions. The grain aphid
      Sitobion avenae is one of the most destructive pests of cereal, directly drawing
      phloem sap and transmitting viruses. In the present study, we first cloned the
      open reading frame (ORF) of Lac 1 from S. avenae, and the putative protein
      sequence was predicted to have a carboxyl-terminal transmembrane domain. We found
      that SaLac1 had higher expression levels in the fourth and adult stages using
      reverse transcription real-time quantitative PCR (RT-qPCR). SaLac 1 was highly
      expressed in the salivary gland and midgut and also in wingless compared with
      winged morphs. After feeding on aphid-resistant wheat with a high total phenol
      content, the expression level of SaLac 1 increased significantly. RNA
      interference (RNAi) by oral feeding successfully inhibited the transcript levels
      of SaLac 1, and the knockdown of Lac 1 significantly decreased the survival rate
      of S. avenae on aphid-resistant wheat. Our study demonstrated that S. avenae Lac1
      was involved in the detoxification of phenolic compounds in wheat and was
      essential for the aphid to adapt to resistant plants.

PMID- 29323437
TI  - Parenteral Nutrition Safety: The Story Continues.
AB  - Parenteral nutrition (PN) is an important therapeutic modality used for a variety
      of indications in adults, children, and infants. PN is a complex, high-alert
      medication that requires appropriate education and ongoing competency assessment
      to ensure a safe process. PN is not recognized by many organizations as a
      medication, which leads to underreporting of errors. This article will provide
      important insight and recommendations to promote a safe PN process.

PMID- 29323438
TI  - Understanding the Unexpected Product Distribution in the Aerial Oxidation of
      Carbene-Stabilized Diphosphorus Complex.
AB  - Oxidation of nonmetallic singlet molecules by oxygen has its own share of
      intricacies. Herein, by means of DFT and ab initio techniques, mechanistic
      details of the aerial oxidation of an N-heterocyclic carbene (NHC) stabilized
      diphosphorus complex are revealed. This particular oxidation process is known to
      produce an unexpected P-P bond containing diphosphorus tetroxide complex, instead
      of the more thermodynamically stable oxo-bridged (P-O-P) compound. These findings
      suggest that the P-P bond containing less stabilized species is a kinetically
      controlled product (KCP) and obtained due to the presence of lower lying
      transition states (TSs) in the pathway leading to its formation, relative to the
      higher lying corresponding minimum-energy crossing points (MECPs) present in the
      pathway involved in the formation of the oxo-bridged species, which is the
      thermodynamically controlled product (TCP). Thus, an intriguing variant of the
      well-known KCP/TCP phenomenon is presented here, in which the KCP is formed not
      by merely traditionally known lower barrier heights of TSs involved in the
      formation of KCP, but by faster transmission of a system through a low barrier TS
      relative to a higher lying MECP. Additionally, the faster kinetics of an
      irreversible unimolecular O-O dissociation step, which avoids the formation of
      the TCP is a contributing factor in dictating the fate of the reaction. The
      insights provided herein may help to understand the oxidation of other P-P
      containing species, such as black phosphorene.

PMID- 29323439
TI  - A Synthetic Binder of Breast Cancer Stem Cells.
AB  - Cancer stem cells (CSCs) are associated with drug resistance, metastasis and
      recurrence of cancer. A synthetic binder of CSCs can provide a valuable tool to
      study the biology of CSCs and a lead to develop imaging, diagnostic and
      therapeutic agents targeting CSCs. Herein, a synthetic ligand (1) that
      specifically binds to CSCs over non-CSCs of breast cancer cells was identified
      for the first time via a cell-binding screening of a chemical library. The ligand
      1 showed specific binding to CD24- /CD44+ /ALDH+ CSC population of MCF-7 and MDA
      MB-231. We have demonstrated that 1-immobilized beads can be used as matrices for
      affinity isolation of 1-binding CSC population from breast cancer cells. The 1
      binding population showed significantly increased expressions of stemness
      associated transcription factors. Importantly, the 1-binding population
      demonstrated accelerated tumor growth in vivo, and the resulting tumor displayed
      an increased migratory activity and high expressions of CSC markers.

PMID- 29323440
TI  - Synthesis of Benzofuranones via Palladium-Catalyzed Intramolecular
      Alkoxycarbonylation of Alkenylphenols.
AB  - Herein, a new catalytic system to synthesize benzofuranones is reported. A
      palladium-catalyzed intramolecular alkoxycarbonylation is employed to generate 3
      substituted-benzofuran-2(3H)-ones from alkenylphenols under mild reaction
      conditions, linked to an ex situ formation of CO from N-formylsaccharin. The
      carefully chosen catalytic system enables an efficient reaction with a novel
      functional group tolerance, despite the high polymerization tendency of the
      starting material.

PMID- 29323441
TI  - A low muscle mass increases mortality in compensated cirrhotic patients with
      sepsis.
AB  - BACKGROUND & AIMS: Severe infections and muscle wasting are both associated to
      poor outcome in cirrhosis. A possible synergic effect of these two entities in
      cirrhotic patients has not been previously investigated. We aimed at analysing if
      a low muscle mass may deteriorate the outcome of cirrhotic patients with sepsis.
      METHODS: Consecutive cirrhotic patients hospitalized for sepsis were enrolled in
      the study. Patients were classified for the severity of liver impairment (Child
      Pugh class) and for the presence of "low muscle mass" (mid-arm muscle
      circumference<5th percentile). The development of complication during
      hospitalization and survival was analysed. RESULTS: There were 74 consecutive
      cirrhotics with sepsis. Forty-three of these patients showed low muscle mass. In
      patients with and without low muscle mass, severity of liver disease and
      characteristics of infections were similar. Mortality tended to be higher in
      patients with low muscle mass (47% vs 26%, P = .06). A multivariate analysis
      selected low muscle mass (P < .01, HR: 3.2, IC: 1.4-4.8) and Child-Pugh C (P <
      .01, HR: 3.3, 95% IC: 1.5-4.9) as independent predictors of in-hospital
      mortality. In Child-Pugh A-B patients, mortality was higher in patients with low
      muscle mass compared with those without (50% vs 16%; P = .01). The mortality rate
      and the incidence of complications in malnourished patients classified in Child
      Pugh A-B were similar to those Child-Pugh C. CONCLUSIONS: Low muscle mass worsen
      prognosis in cirrhotic patients with severe infections. This is particularly
      evident in patients with Child A-B cirrhosis in whom the coexistence of low
      muscle mass and sepsis caused a negative impact on mortality similar to that
      observable in all Child C patients with sepsis.

PMID- 29323442
TI  - Mental health inpatients' and staff members' suggestions for reducing physical
      restraint: A qualitative study.
AB  - : WHAT IS KNOWN ON THE SUBJECT?: Restraint has negative psychological, physical
      and relational consequences for mental health patients and staff. Restraint
      reduction interventions have been developed (e.g., "Safewards"). Limited
      qualitative research has explored suggestions on how to reduce physical restraint
      (and feasibility issues with implementing interventions) from those directly
      involved. WHAT DOES THIS PAPER ADD TO EXISTING KNOWLEDGE?: This paper explores
      mental health patients' and staff members' suggestions for reducing physical
      restraint, whilst addressing barriers to implementing these. Findings centred on
      four themes: improving communication and relationships; staffing factors;
      environment and space; and activities and distraction. Not all suggestions are
      addressed by currently available interventions. Barriers to implementation were
      identified, centring on a lack of time and/or resources; with the provision of
      more time for staff to spend with patients and implement interventions seen as
      essential to reducing physical restraint. WHAT ARE THE IMPLICATIONS FOR
      PRACTICE?: Improving communication and relationships between staff/patients,
      making staffing-related changes, improving ward environments and providing
      patient activities are central to restraint reduction in mental healthcare.
      Fundamental issues related to understaffing, high staff turnover, and lack of
      time and resources need addressing in order for suggestions to be successfully
      implemented. ABSTRACT: Introduction Physical restraint has negative consequences
      for all involved, and international calls for its reduction have emerged. Some
      restraint reduction interventions have been developed, but limited qualitative
      research explores suggestions on how to reduce physical restraint (and
      feasibility issues with implementation) from those directly involved. Aims To
      explore mental health patients' and staff members' suggestions for reducing
      physical restraint. Methods Interviews were conducted with 13 inpatients and 22
      staff members with experience of restraint on adult mental health inpatient wards
      in one UK National Health Service Trust. Results Findings centred on four
      overarching themes: improving communication and relationships between
      staff/patients; making staff-related changes; improving ward environments/spaces;
      and having more activities. However, concerns were raised around
      practicalities/feasibility of their implementation. Discussion Continued research
      is needed into best ways to reduce physical restraint, with an emphasis on
      feasibility/practicality and how to make time in busy ward environments.
      Implications for Practice Improving communication and relationships between
      staff/patients, making staffing-related changes, improving ward environments and
      providing patient activities are central to restraint reduction in mental
      healthcare. However, fundamental issues related to understaffing, high staff
      turnover and lack of time/resources need addressing in order for these
      suggestions to be successfully implemented.

PMID- 29323443
TI  - Dicationic E4 Chains (E=P, As, Sb, Bi) Embedded in the Coordination Sphere of
      Transition Metals.
AB  - The oxidation chemistry of the complexes [{CpMo(CO)2 }2 (MU,eta2 :eta2 -E2 )]
      (E=P (A), As (B), Sb (C), Bi (D)) is compared. The oxidation of A-D with [Thia]+
      (=[C12 H8 S2 ]+ ) results in the selective formation of the dicationic E4
      complexes [{CpMo(CO)2 }4 (MU4 ,eta2 :eta2 :eta2 :eta2 -E4 )]2+ (E=P (1), As (2),
      Sb (3), Bi (4)), stabilized by four [CpMo(CO)2 ] fragments. The formation of the
      corresponding monocations [A]+ , [C]+ , and [D]+ could not be detected by cyclic
      voltammetry, EPR, or NMR spectroscopy. This finding suggests that dimerization is
      fast and that there is no dissociation in solution, which was also predicted by
      DFT calculations. However, EPR measurements of 2 confirmed the presence of small
      amounts of the radical cation [B]+ in solution. Single-crystal X-ray diffraction
      revealed that the products 1 and 2 feature a zigzag E4 chain in the solid state
      while 3 and 4 bear a central E4 cage with a distorted "butterfly-like" geometry.
      Additionally, 1 can be easily and reversibly converted into a symmetric and an
      unsymmetric form.

PMID- 29323444
TI  - Impact of new diagnostic criteria for gestational diabetes.
AB  - AIM: In January 2015, the diagnostic and therapeutic criteria for gestational
      diabetes changed, with the goal of increasing the sensitivity of diagnosis and
      improving overall glycemic control, and thus reducing adverse pregnancy outcomes.
      Our primary aim was to evaluate the effect of the new guidelines on the incidence
      of diagnosis of gestational diabetes and the incidence of therapeutic
      interventions. Our secondary aim was to look at the incidence of adverse
      pregnancy outcomes. METHODS: A retrospective clinical audit was conducted at a
      regional hospital to compare the incidence of gestational diabetes, and the
      specific maternal and neonatal outcomes before and after the change in guidelines
      was implemented. Data were collected via chart review for a 6-month period before
      and after the change in guidelines in January 2015. Data collected included
      demographics, neonatal and maternal outcomes, and the treatment type used for
      patients diagnosed with gestational diabetes. RESULTS: There was a significant
      increase in the incidence of diagnosis of gestational diabetes (9.8-19.6%; P <
      0.001), and an overall increase in the use of pharmacological treatments for
      gestational diabetes. There was no significant difference in the incidence of the
      adverse outcomes measured, including cesarean delivery and macrosomia. There was
      no significant change in mean fetal weight. CONCLUSION: Despite a doubling of the
      incidence of diagnosis of gestational diabetes, and a consequent increase in
      pharmacological interventions, the change in diagnostic and therapeutic criteria
      did not significantly reduce the neonatal or maternal adverse outcomes measured.

PMID- 29323446
TI  - Response to 'Gum chewing aids bowel function return and analgesic requirements
      after bowel surgery: a randomised controlled trial'.

PMID- 29323447
TI  - Solvation-Induced Changes in the Mechanism of Alcohol Oxidation at Gold/Titania
      Nanocatalysts in the Aqueous Phase versus Gas Phase.
AB  - Gold/titania catalysts are widely used for key reactions, notably including the
      selective oxidation of alcohols in the liquid phase. Our large-scale ab initio
      simulations disclose that the liquid-phase reaction mechanism is distinctly
      different from that in the gas phase because of active participation of water
      molecules. While concerted charge transfers related to O2 splitting and
      abstraction of both protonic and hydridic hydrogens are enforced under dry
      conditions, stepwise charge transfer is preferred in the condensed phase.
      Dissociation of reactive water molecules and subsequent Grotthuss migration of
      protonic defects, H+ (aq), allows for such a decoupling of the oxidation process,
      both in time and space. It is expected that these observations are paradigmatic
      for heterogeneous catalysis in aqueous phases.

PMID- 29323448
TI  - Catalytic Desymmetrizing Dehydrogenation of 4-Substituted Cyclohexanones through
      Enamine Oxidation.
AB  - A desymmetrizing dehydrogenation process catalyzed by a chiral primary amine is
      described herein. The reaction proceeds through the oxidation of a ketone enamine
      by IBX and enables the highly enantioselective desymmetrization of 4-substituted
      cyclohexanones with the generation of chiral 4-substituted cyclohexenones
      containing a remote gamma-stereocenter.

PMID- 29323449
TI  - Enhanced Ultrafast Nonlinear Optical Response in Ferrite Core/Shell
      Nanostructures with Excellent Optical Limiting Performance.
AB  - Nonlinear optical nanostructured materials are gaining increased interest as
      optical limiters for various applications, although many of them suffer from
      reduced efficiencies at high-light fluences due to photoinduced deterioration.
      The nonlinear optical properties of ferrite core/shell nanoparticles showing
      their robustness for ultrafast optical limiting applications are reported. At 100
      fs ultrashort laser pulses the effective two-photon absorption (2PA) coefficient
      shows a nonmonotonic dependence on the shell thickness, with a maximum value
      obtained for thin shells. In view of the local electric field confinement, this
      indicates that core/shell is an advantageous morphology to improve the nonlinear
      optical parameters, exhibiting excellent optical limiting performance with
      effective 2PA coefficients in the range of 10-12 cm W-1 (100 fs excitation), and
      optical limiting threshold fluences in the range of 1.7 J cm-2 . These values are
      comparable to or better than most of the recently reported optical limiting
      materials. The quality of the open aperture Z-scan data recorded from repeat
      measurements at intensities as high as 35 TW cm-2 , indicates their considerably
      high optical damage thresholds in a toluene dispersion, ensuring their robustness
      in practical applications. Thus, the high photostability combined with the
      remarkable nonlinear optical properties makes these nanoparticles excellent
      candidates for ultrafast optical limiting applications.

PMID- 29323450
TI  - Theoretical Investigation of the Infrared Spectrum of 5-Bromo-2,4
      pentadiynenitrile from a CCSD(T)/B3LYP Anharmonic Potential.
AB  - On the grounds of a hybrid CCSD(T)/B3LYP/aug-cc-pVTZ anharmonic potential and the
      use of a variational and variational-perturbational methods, the IR spectra of 5
      bromo-2,4-pentadiynenitrile (BrC5 N) is revisited in the mid-infrared region up
      to 4500 cm-1 . A position and intensity analysis of our theoretical results allow
      us to assign the fundamental bands together with their combinations and
      overtones, in the aforementioned range of frequencies. The main objective of this
      work is to give an "a priori" complete IR spectrum of BrC5 N, which can be used
      as a guide for the low-intensity bands in areas not completely studied so far.

PMID- 29323452
TI  - Laparoscopic lateral pelvic lymph node dissection for rectal cancer - a video
      vignette.

PMID- 29323451
TI  - Microvascular involvement in Systemic Sclerosis and Systemic Lupus Erythematosus.
AB  - Microvascular changes play central roles in the pathophysiology of systemic
      sclerosis (SSc) and systemic lupus erythematosus (SLE), and represent major
      causes of morbidity and mortality in these patients. Therefore, clinical tools
      that can assess the microvasculature are of great importance both at the time of
      diagnosis and follow up of these cases. These tools include capillaroscopy, laser
      imaging techniques, infrared thermography and iontophoresis. In this review, we
      examined the clinical manifestations and pathobiology of microvascular
      involvement in SSc and SLE as well as the methodologies used to evaluate the
      microvasculature. This article is protected by copyright. All rights reserved.

PMID- 29323453
TI  - Patterning Graphene Surfaces with Iron-Oxide-Embedded Mesoporous Polypyrrole and
      Derived N-Doped Carbon of Tunable Pore Size.
AB  - This study develops a novel strategy, based on block copolymer self-assembly in
      solution, for preparing two-dimensional (2D) graphene-based mesoporous
      nanohybrids with well-defined large pores of tunable sizes, by employing
      polystyrene-block-poly(ethylene oxide) (PS-b-PEO) spherical micelles as the pore
      creating template. The resultant 2D nanohybrids possess a sandwich-like structure
      with Fe2 O3 nanoparticle-embedded mesoporous polypyrrole (PPy) monolayers grown
      on both sides of reduced graphene oxide (rGO) nanosheets (denoted as mPPy-Fe2 O3
      @rGO). Serving as supercapacitor electrode materials, the 2D ternary nanohybrids
      exhibit controllable capacitive performance depending on the pore size, with high
      capacitance (up to 1006 F/g at 1 A/g), good rate performance (750 F/g at 20 A/g)
      and excellent cycling stability. Furthermore, the pyrolysis of mPPy-Fe2 O3 @rGO
      at 800  degrees C yields 2D sandwich-like mesoporous nitrogen-doped carbon/Fe3 O4
      /rGO (mNC-Fe3 O4 @rGO). The mNC-Fe3 O4 @rGO nanohybrids with a mean pore size of
      12 nm show excellent electrocatalytic activity as an oxygen reduction reaction
      (ORR) catalyst with a four-electron transfer nature, a high half-wave-potential
      of +0.84 V and a limiting current density of 5.7 mA/cm2 , which are well
      comparable with those of the best commercial Pt/C catalyst. This study takes
      advantage of block copolymer self-assembly for the synthesis of 2D
      multifunctional mesoporous nanohybrids, and helps to understand the control of
      their structures and electrochemical performance.

PMID- 29323454
TI  - A Bifunctional Highly Efficient FeNx /C Electrocatalyst.
AB  - Herein, a type of Fe, N-codoped carbon electrocatalyst (FeNx /C, Fe-N-BCNT#BP)
      containing bamboo carbon nanotubes and displaying bifunctional high catalytic
      efficiency for both oxygen reduction reaction (ORR) and carbon dioxide reduction
      reaction (CO2RR) is reported. It shows high electrocatalytic activity and
      stability for both the ORR process with onset potential of 1.03 VRHE in alkaline
      and the CO2RR to CO with high faradic efficiency up to 90% and selectivity of
      about 100% at low overpotential of 0.49 V. For CO2RR to CO, it is revealed that
      Fe3 C is active but the activity of FeNx centers is lower than that of C-N-based
      centers, contrary with that observed for ORR. Due to its low cost and high
      electrocatalytic performance for these two reduction reactions, the obtained
      catalyst is very promising for extensive application in future. The revealed huge
      activity difference of the same types of active sites for different reactions can
      efficiently guide the synthesis of advanced materials with multifunction.

PMID- 29323455
TI  - Selenocysteine inhibits human osteosarcoma cells growth through triggering
      mitochondrial dysfunction and ROS-mediated p53 phosphorylation.
AB  - Osteosarcoma represents the most common primary malignant bone tumor in children
      and adolescents, which shows severe resistance toward standard chemotherapy
      because of high invasive capacity and growing incidence. Selenocysteine (SeC) is
      a naturally available Se-containing amino acid that displays splendid anticancer
      activities against several human tumors. However, little information about SeC
      induced growth inhibition against human osteosarcoma is available. Herein, the
      anticancer efficiency and underlying mechanism of SeC against human osteosarcoma
      were evaluated in vitro and in vivo. The results revealed that SeC significantly
      inhibited MG-63 human osteosarcoma cells growth in vitro through induction of S
      phase arrest and apoptosis, as reflected by the decrease of cyclin A and CDK-2,
      PARP cleavage, and caspases activation. SeC treatment also resulted in
      mitochondrial dysfunction through affecting Bcl-2 family expression. Moreover,
      SeC triggered p53 phosphorylation by inducing reactive oxygen species (ROS)
      overproduction. ROS inhibition effectively blocked SeC-induced cytotoxicity and
      p53 phosphorylation. Importantly, MG-63 human osteosarcoma xenograft growth in
      nude mice was significantly suppressed in vivo through triggering apoptosis and
      p53 phosphorylation. These results indicated that SeC had the potential to
      inhibit human osteosarcoma cells growth in vitro and in vivo through triggering
      mitochondrial dysfunction and ROS-mediated p53 phosphorylation, which validated
      the potential application of Se-containing compounds in treatment of human
      osteosarcoma.

PMID- 29323456
TI  - Tuning the Carrier Confinement in GeS/Phosphorene van der Waals Heterostructures.
AB  - Van der Waals (vdW) heterostructures, which have the advantage of integrating
      excellent properties of the stacked 2D materials by vdW interactions, have gained
      increasing attention recently. In this work, within the framework of density
      functional theory calculations, the electronic properties of vdW heterostructure
      composed of phosphorene (BP) in black phosphorus phase and GeS monolayer are
      systematically explored. The results show that the carriers are not separated for
      both lattice-match and lattice-mismatch heterostructures. For the lattice-match
      heterostructure, it is found that changing monolayer of GeS to bilayer can
      increase the energy difference of valence band offsets between GeS and BP, thus
      realizing electron-hole separation. For the lattice-mismatch heterostructure,
      altering the layer distance can transform the heterostructure into a typical type
      I alignment, but applying the electric field or doping with 2, 3, 5, 6
      tetrafluoro-7, 7, 8, 8-tetracyanoquinodimethane (F4TCNQ) can make it display a
      perfect desirable type-II alignment, where holes migration and electrons transfer
      are revealed to account respectively for the phenomenon of carrier separation. It
      is believed that the work would greatly enlarge the potential application of the
      BP-based heterostructures in photoelectronics and further stimulate the
      investigation enthusiasms on other fashionable heterostructures and even
      unassuming heterostructures in which the charming electronic properties can be
      modulated to emerge by various general methods.

PMID- 29323458
TI  - Metal-Organic Framework Encapsulation for the Preservation and Photothermal
      Enhancement of Enzyme Activity.
AB  - Interfacing biomolecules with functional materials is a key strategy toward
      achieving externally-triggered biological function. The rational integration of
      functional proteins, such as enzymes, with plasmonic nanostructures that exhibit
      unique optical properties such as photothermal effect provides a means to
      externally control the enzyme activity. However, due to the labile nature of
      enzymes, the photothermal effect of plasmonic nanostructures is mostly utilized
      for the enhancement of the biocatalytic activity of thermophilic enzymes. In
      order to extend and utilize the photothermal effect to a broader class of
      enzymes, a means to stabilize the immobilized active protein is essential.
      Inspired by biomineralization for the encapsulation of soft tissue within
      protective exteriors in nature, metal-organic framework is utilized to stabilize
      the enzyme. This strategy provides an effective route to enhance and externally
      modulate the biocatalytic activity of enzymes bound to functional nanostructures
      over a broad range of operating environments that are otherwise hostile to the
      biomolecules.

PMID- 29323457
TI  - Impact of subchronic exposure to triclosan and/or fluoride on estrogenic activity
      in immature female rats: The expression pattern of calbindin-D9k and estrogen
      receptor alpha genes.
AB  - This study explored the influence of triclosan (TCS) in the absence and presence
      of sodium fluoride (NaF) on estrogenic activity and thyroid function of
      adolescent female rats. The results indicated that the individual exposure to TCS
      evoked a significant decline in T3 and T4 but the levels of estradiol, FSH, and
      LH were significantly elevated beside marked up regulation of calbindin-D9k and
      estrogen alpha mRNA expression. On the other hand, the single exposure to NaF
      causes insignificant changes in thyroid hormones, but evoked a trend toward an
      increase in both estradiol and LH levels. No significant differences in the TSH
      level were recorded among the experimental groups. The joint exposure to TCS and
      NaF induced a significant improvement in thyroid and reproductive hormone levels.
      Overall, these findings revealed that exposure to TCS resulted in significant
      endocrine and reproductive alterations in immature female rats, while TCS + NaF
      coexposure resulted in lessening most effects.

PMID- 29323459
TI  - Reliability and safety of transnasal compared to conventional endoscopy for
      detecting oesophageal varices in cirrhotic patients.
AB  - BACKGROUND & AIMS: Unsedated transnasal endoscopy may be used for detecting
      oesophageal varices. However, few studies evaluated feasibility and accuracy of
      this technique. We aimed to evaluate accuracy, interobserver agreement and safety
      of the transnasal ultrathin compared to conventional endoscopy in patients with
      cirrhosis. METHODS: This cross-sectional study included consecutive patients
      referred for screening or surveillance of oesophageal varices. Patients underwent
      unsedated transnasal and sedated conventional endoscopies at the same day, which
      were recorded in a digital video file and randomly analysed by two double-blinded
      endoscopists. High-risk varices were defined by the presence of large calibre or
      red wale marks. Accuracy, interobserver agreement and safety of transnasal were
      compared to conventional endoscopy. RESULTS: One hundred and thirty-three
      cirrhotic patients (48% male, aged of 60 +/- 5, 34% Child-Pugh B/C and 71% of
      cases for variceal screening) were included in the study. The prevalence of
      oesophageal varices and high-risk oesophageal varices were 59% (n = 79) and 29%
      (n = 39) respectively. For the presence of oesophageal varices, transnasal GIE
      yielded sensitivity of 94% [95% Confidence Interval, CI 88-99], specificity of
      89% [81-97] as well as positive and negative predictive value of 93% and 91%
      respectively. A satisfactory interobserver agreement was observed for the
      presence of oesophageal varices (kappa = 0.89) and high-risk varices (kappa =
      0.65). No serious adverse events were recorded; transnasal GIE was safe and
      significantly associated with lower rates of hypoxaemia (P < .0001) and
      hypotension (P < .0001) compared to conventional endoscopy. CONCLUSIONS:
      Unsedated transnasal endoscopy was safe and had an excellent accuracy and high
      interobserver agreement for detecting oesophageal varices and for identifying
      high-risk varices in cirrhotic patients.

PMID- 29323460
TI  - A New Fluorogenic Probe for the Detection of endo-beta-N-Acetylglucosaminidase.
AB  - We developed a fluorescence-quenching-based assay system to determine the
      hydrolysis activity of endo-beta-N-acetylglucosaminidases (ENGases). The
      pentasaccharide derivative 1 was labeled with an N-methylanthraniloyl group as a
      reporter dye at the non-reducing end and with a 2,4-dinitrophenyl group as a
      quencher molecule at the reducing end. This derivative is hydrolyzed by ENGase,
      resulting in an increase in fluorescence intensity. Thus, the fluorescence signal
      is directly proportional to the amount of the tetrasaccharide derivative, hence
      allowing ENGase activity to be evaluated easily and quantitatively. Using this
      system, we succeeded in measuring the hydrolysis activities of ENGases and thus
      the inhibitory activities of known inhibitors. We confirmed that this assay
      system is suitable for high-throughput screening for potential inhibitors of
      human ENGase that might serve as therapeutic agents for the treatment of N
      glycanase 1 (NGLY1) deficiency.

PMID- 29323462
TI  - Letter to 'Repair of damaged ligaments with tissue fixation system minisling is
      sufficient to cure major prolapse in all three compartments: 5-year data'.

PMID- 29323463
TI  - Ultrathin Bismuth Nanosheets as a Highly Efficient CO2 Reduction Electrocatalyst.
AB  - Electrochemical reduction of CO2 to value-added products is an important and
      challenging reaction for sustainable energy study. Herein, bismuth nanosheets
      with thickness of around 10 nm were prepared through the electrochemical
      reduction of Bi3+ . Ultrathin Bi nanosheets with numerous low-coordination sites
      can efficiently reduce CO2 to formate in aqueous solution. Within the potential
      range of -0.9 to -1.2 V vs. reversible hydrogen electrode (RHE), the faradaic
      efficiency of formate is over 90 %, outperforming many Bi catalysts. At -0.7 V,
      the Bi nanosheets exhibit much higher current for formate generation than that of
      bulk Bi, attributed to a high surface area and also modified intrinsic electronic
      properties brought about by the ultrathin structure. DFT calculations demonstrate
      that Bi nanosheets have much higher density of states at the Fermi level compared
      to bulk Bi, favoring improved CO2 reduction on Bi nanosheets. At -1.0 V, Bi
      nanosheets exhibit high selectivity for formate and excellent stability during 5
      h of electrolysis.

PMID- 29323461
TI  - N-Benzyl Substitution of Polyhydroxypyrrolidines: The Way to Selective Inhibitors
      of Golgi alpha-Mannosidase II.
AB  - Inhibition of the biosynthesis of complex N-glycans in the Golgi apparatus
      influences progress of tumor growth and metastasis. Golgi alpha-mannosidase II
      (GMII) has become a therapeutic target for drugs with anticancer activities. One
      critical task for successful application of GMII drugs in medical treatments is
      to decrease their unwanted co-inhibition of lysosomal alpha-mannosidase (LMan), a
      weakness of all known potent GMII inhibitors. A series of novel N-substituted
      polyhydroxypyrrolidines was synthesized and tested with modeled GH38 alpha
      mannosidases from Drosophila melanogaster (GMIIb and LManII). The most potent
      structures inhibited GMIIb (Ki =50-76 MUm, as determined by enzyme assays) with a
      significant selectivity index of IC50 (LManII)/IC50 (GMIIb) >100. These compounds
      also showed inhibitory activities in in vitro assays with cancer cell lines
      (leukemia, IC50 =92-200 MUm) and low cytotoxic activities in normal fibroblast
      cell lines (IC50 >200 MUm). In addition, they did not show any significant
      inhibitory activity toward GH47 Aspergillus saitoialpha1,2-mannosidase. An
      appropriate stereo configuration of hydroxymethyl and benzyl functional groups on
      the pyrrolidine ring of the inhibitor may lead to an inhibitor with the required
      selectivity for the active site of a target alpha-mannosidase.

PMID- 29323464
TI  - Light-Driven Shape-Memory Porous Films with Precisely Controlled Dimensions.
AB  - Shape-memory polymers (SMPs) are an intriguing class of smart materials
      possessing reversible shape change and recovery capabilities. Effective routes to
      shape-memory porous films (SMPFs) are few and limited in scope owing to the
      difficulty in manipulating the shape change of pores by conventional methods.
      Herein we report an unconventional strategy for crafting light-driven SMPFs by
      judiciously constructing highly ordered porous films via a facile "breath figure"
      approach, followed by sequential vapor crosslinking and nondestructive
      directional light manipulation. Micropores can thus be transformed into other
      shapes including rectangle, rhombus and size-reduced micropores at room
      temperature. The transformed micropores can be reverted to their original shapes
      by either thermal annealing or UV irradiation. As such, this strategy expands the
      rich diversity of SMPs accessible.

PMID- 29323465
TI  - Multiplexed Digital mRNA Expression Analysis Profiles System-Wide Changes in mRNA
      Abundance and Responsiveness of UPR-Specific Gene Expression Changes During Batch
      Culture of Recombinant Chinese Hamster Ovary Cells.
AB  - The unfolded protein response (UPR) signaling pathway is viewed as critical for
      setting the effectiveness of recombinant protein expression in CHO cells. In this
      study, Nanostring nCounter technology is used to study expression of a group of
      genes associated with cellular processes linked to UPR activation under ER stress
      and the changing environment of a batch culture. Time course induction of ER
      stress, using tunicamycin (TM), shows a group of genes such as Chop, Trb3,
      Sqstm1, Grp78, and Herpud1 respond rapidly to TM inhibition of N-glycosylation,
      while others such as Atf5, Odz4, and Birc5 exhibits a delayed response. In batch
      culture, expression of "classical" UPR markers only increases when cells enter
      decline phase. In addition to providing a detailed analysis of the expression of
      process-relevant UPR markers during batch culture and in response to imposed
      chemical stress, we also highlighted six genes (Herpud1, Odz4, Sqstm1, Trb3,
      Syvn1, and Birc5) associated with the perception of ER stress responses in
      recombinant CHO cells. Herpud1 (involved in ER-associated degradation) exhibits a
      rapid (primary) response to stress and its relationship (and that of the other
      five genes) to the overall cellular UPR may identify novel targets to modulate
      recombinant protein production in CHO cells.

PMID- 29323466
TI  - Design and Synthesis of A-Ring Simplified Pyripyropene A Analogues as Potent and
      Selective Synthetic SOAT2 Inhibitors.
AB  - Currently, pyripyropene A, which is isolated from the culture broth of
      Aspergillus fumigatus FO-1289, is the only compound known to strongly and
      selectively inhibit the isozyme sterol O-acyltransferase 2 (SOAT2). To aid in the
      development of new cholesterol-lowering or anti-atherosclerotic agents, new A
      ring simplified pyripyropene A analogues have been designed and synthesized based
      on total synthesis, and the results of structure-activity relationship studies of
      pyripyropene A. Among the analogues, two A-ring simplified pyripyropene A
      analogues exhibited equally efficient SOAT2 inhibitory activity to that of
      natural pyripyropene A. These new analogues are the most potent and selective
      SOAT2 inhibitors to be used as synthetic compounds and attractive seed compounds
      for the development of drug for dyslipidemia, including atherosclerotic disease
      and steatosis.

PMID- 29323467
TI  - Interactions between Clinically Used Bisphosphonates and Bone Mineral: from
      Coordination Chemistry to Biomedical Applications and Beyond.
AB  - Bisphosphonates (BPs) are well-established, widely used first-choice drugs for
      bone-related diseases and are one of the few classes of molecules for selective
      bone targeting. Their binding to calcium cations within hydroxyapatite (HA) is a
      key physicochemical event that takes place on the bone surface. It is the
      starting point for a cascade of biochemical reactions and cellular effects that
      lead to the pharmacological activity of BPs. The phenomenon has been known for
      years, yet its physicochemical nature is still not fully understood. In
      particular, the adsorption/release processes and structure-function relationships
      of BPs remain to be clarified. These are elementary, yet crucial factors, which
      should influence the design and development of new delivery tools or drugs with
      improved characteristics. This review summarizes the current understanding of the
      chemical interactions between clinically used BPs and bone mineral, starting from
      basic Ca2+ coordination chemistry through to interactions with hydroxyapatite,
      nanocrystalline apatites, and natural bone mineral.

PMID- 29323468
TI  - In Silico Studies Designed to Select Sesquiterpene Lactones with Potential
      Antichagasic Activity from an In-House Asteraceae Database.
AB  - Chagas disease is an endemic disease caused by Trypanosoma cruzi, which affects
      more than eight million people, mostly in the Americas. A search for new
      treatments is necessary to control and eliminate this disease. Sesquiterpene
      lactones (SLs) are an interesting group of secondary metabolites characteristic
      of the Asteraceae family that have presented a wide range of biological
      activities. From the ChEMBL database, we selected a diverse set of 4452, 1635,
      and 1322 structures with tested activity against the three T. cruzi parasitic
      forms: amastigote, trypomastigote, and epimastigote, respectively, to create
      random forest (RF) models with an accuracy of greater than 74 % for cross
      validation and test sets. Afterward, a ligand-based virtual screen of the entire
      SLs of the Asteraceae database stored in SistematX (1306 structures) was
      performed. In addition, a structure-based virtual screen was also performed for
      the same set of SLs using molecular docking. Finally, using an approach combining
      ligand-based and structure-based virtual screening along with the equations
      proposed in this study to normalize the probability scores, we verified
      potentially active compounds and established a possible mechanism of action.

PMID- 29323469
TI  - Self-Collapsing of Single Molecular Poly-Propylene Oxide (PPO) in a 3D DNA
      Network.
AB  - On the basis of DNA self-assembly, a thermal responsive polymer polypropylene
      oxide (PPO) is evenly inserted into a rigid 3D DNA network for the study of
      single molecular self-collapsing process. At low temperature, PPO is hydrophilic
      and dispersed uniformly in the network; when elevating temperature, PPO becomes
      hydrophobic but can only collapse on itself because of the fixation and
      separation of DNA rigid network. The process has been characterized by
      rheological test and Small Angle X-Ray Scattering test. It is also demonstrated
      that this self-collapsing process is reversible and it is believed that this
      strategy could provide a new tool to study the nucleation-growing process of
      block copolymers.

PMID- 29323470
TI  - Alkylation-, Heating-, and Doping-Induced Emission Enhancement of a Polyaromatic
      Tube in the Solid State.
AB  - A polyaromatic tube with a subnanometer-sized cavity was efficiently prepared on
      a gram-scale through the stereo-controlled cyclotrimerization of a
      diphenylanthracene derivative as a key step. The facile exterior alkylation of
      the polyaromatic framework leads to a moderately fluorescent tube (R=-OC10 H21 ;
      PhiF =20 %) in the solid state. The emission intensity of the solid-state alkyl
      substituted tube is remarkably enhanced upon heating (up to 1.6 times, PhiF =31
      %) as well as doping with fluorescent dyes (up to 4.2 times, PhiF =83 %) through
      efficient energy transfer.

PMID- 29323471
TI  - Synthesis of N-Substituted Iminosugar Derivatives and Evaluation of Their
      Immunosuppressive Activities.
AB  - It is important to find more effective and safer immunosuppressants, because
      clinically used immunosuppressive agents have significant side effects. A series
      of N-substituted iminosugar derivatives were designed and synthesized, and their
      immunosuppressive effects were evaluated by the CCK-8 assay. The results revealed
      that iminosugars 10 e and 10 i, that is, (3R,4S)-1-(4
      heptyloxylphenylethyl)pyrrolidine-3,4-diol and (3R,4S)-1-[2-(2-chloro-4-(p
      tolylthio)-phenyl-1-yl)ethyl]pyrrolidine-3,4-diol, respectively, exhibited the
      strongest inhibitory effects on mouse splenocyte proliferation (IC50 =2.16 and
      2.48 MUm, respectively), whereas the iminosugars containing an amide group near
      the hydrophilic head (compounds 10 j-n) exhibited no inhibitory effects. Further
      studies revealed that the inhibitory effects on splenocyte proliferation may have
      come from the suppression of both IFN-gamma and IL-4 cytokines. Our results
      suggest that synthetic iminosugars, especially compounds 10 e and 10 i, hold
      potential as immunosuppressive agents.

PMID- 29323472
TI  - Integrated Analysis of the Transcriptome and Metabolome of Corynebacterium
      glutamicum during Penicillin-Induced Glutamic Acid Production.
AB  - Corynebacterium glutamicum is known for its ability to produce glutamic acid and
      has been utilized for the fermentative production of various amino acids.
      Glutamic acid production in C. glutamicum is induced by penicillin. In this
      study, the transcriptome and metabolome of C. glutamicum is analyzed to
      understand the mechanism of penicillin-induced glutamic acid production.
      Transcriptomic analysis with DNA microarray revealed that expression of some
      glycolysis- and TCA cycle-related genes, which include those encoding the enzymes
      involved in conversion of glucose to 2-oxoglutaric acid, is upregulated after
      penicillin addition. Meanwhile, expression of some TCA cycle-related genes,
      encoding the enzymes for conversion of 2-oxoglutaric acid to oxaloacetic acid,
      and the anaplerotic reactions decreased. In addition, expression of NCgl1221 and
      odhI, encoding proteins involved in glutamic acid excretion and inhibition of the
      2-oxoglutarate dehydrogenase, respectively, is upregulated. Functional category
      enrichment analysis of genes upregulated and downregulated after penicillin
      addition revealed that genes for signal transduction systems are enriched among
      upregulated genes, whereas those for energy production and carbohydrate and amino
      acid metabolisms are enriched among the downregulated genes. As for the
      metabolomic analysis using capillary electrophoresis time-of-flight mass
      spectrometry, the intracellular content of most metabolites of the glycolysis and
      the TCA cycle decreased dramatically after penicillin addition. Overall, these
      results indicate that the cellular metabolism and glutamic acid excretion are
      mainly optimized at the transcription level during penicillin-induced glutamic
      acid production by C. glutamicum.

PMID- 29323473
TI  - ZnO Nanorod-Induced Heteroepitaxial Growth of SOD Type Co-Based Zeolitic
      Imidazolate Framework Membranes for H2 Separation.
AB  - Up to now, the fabrication of well-intergrown Co-based zeolitic imidazolate
      framework (ZIF) membranes on porous tubular supports is still a major challenge.
      We report here a heteroepitaxial growth for preparing well-intergrown Co-based
      ZIFs (ZIF-67 and ZIF-9) tubular membranes with high performance and excellent
      thermal stability by employing a thin layer of ZnO nanorods acting as both
      nucleation centers and anchor sites for the growth of metal-organic framework
      membranes. The results show that well-intergrown Co-ZIF-67 and Co-ZIF-9 membranes
      are successfully achieved on the ZnO nanorod-modified porous ceramic tubes. This
      highly active heteroepitaxial growth may be attributed to the fact that the
      (Zn,Co) hydroxy double salt intermediate produced in situ from ZnO nanorods acts
      as heteroseeds and enables the uniform growth of Co-based membranes. The H2/CO2
      selectivity of the as-prepared Co-ZIF-9 tubular membrane could reach about 23.8
      and the H2/CH4 selectivity of Co-ZIF-67 tubular membrane is as high as 45.4.
      Moreover, the membranes demonstrate excellent stability because of the ZnO
      nanorods as linkers between the membrane and substrate.

PMID- 29323474
TI  - Caspase-1 Specific Light-Up Probe with Aggregation-Induced Emission
      Characteristics for Inhibitor Screening of Coumarin-Originated Natural Products.
AB  - Caspase-1 is a key player in pyroptosis and inflammation. Caspase-1 inhibition is
      found to be beneficial to various diseases. Coumarin-originated natural products
      have an anti-inflammation function, but their direct inhibition effect to caspase
      1 remains unexplored. To evaluate their interactions, the widely used commercial
      coumarin-based probe (Ac-YVAD-AMC) is not suitable, as the background signal from
      coumarin-originated natural products could interfere with the screening results.
      Therefore, fluorescent probes using a large Stokes shift could help solve this
      problem. In this work, we chose the fluorophore of tetraphenylethylene-thiophene
      (TPETH) with aggregation-induced emission characteristics and a large Stokes
      shift of about 200 nm to develop a molecular probe. Bioconjugation between TPETH
      and hydrophilic peptides (DDYVADC) through a thiol-ene reaction generated a light
      up probe, C1-P3. The probe has little background signal in aqueous media and
      exerts a fluorescent turn-on effect in the presence of caspase-1. Moreover, when
      evaluating the inhibition potency of coumarin-originated natural products, the
      new probe could generate a true and objective result but not for the commercial
      probe (Ac-YVAD-AMC), which is evidenced by HPLC analysis. The quick light-up
      response and accurate screening results make C1-P3 very useful in fundamental
      study and inhibitior screening toward caspase-1.

PMID- 29323475
TI  - Broadband Tunable THz Absorption with Singular Graphene Metasurfaces.
AB  - By exploiting singular spatial modulations of the graphene conductivity, we
      design a broadband, tunable THz absorber whose efficiency approaches the
      theoretical upper bound for a wide absorption band with a fractional bandwidth of
      185%. Strong field enhancement is exhibited by the modes of this extended
      structure, which is able to excite a wealth of high-order surface plasmons,
      enabling deeply subwavelength focusing of incident THz radiation. Previous
      studies have shown that the conductivity can be modulated at GHz frequencies,
      which might lead to the development of efficient high-speed broadband switching
      by an atomically thin layer.

PMID- 29323476
TI  - Localized Electrothermal Annealing with Nanowatt Power for a Silicon Nanowire
      Field-Effect Transistor.
AB  - This work investigates localized electrothermal annealing (ETA) with extremely
      low power consumption. The proposed method utilizes, for the first time,
      tunneling-current-induced Joule heat in a p-i-n diode, consisting of p-type,
      intrinsic, and n-type semiconductors. The consumed power used for dopant control
      is the lowest value ever reported. A metal-oxide-semiconductor field-effect
      transistor (MOSFET) composed of a p-i-n silicon nanowire, which is a substructure
      of a tunneling FET (TFET), was fabricated and utilized as a test platform to
      examine the annealing behaviors. A more than 2-fold increase in the on-state
      (ION) current was achieved using the ETA. Simulations are conducted to
      investigate the location of the hot spot and how its change in heat profile
      activates the dopants.

PMID- 29323477
TI  - Synthesis of Structurally Defined Cationic Polythiophenes for DNA Binding and
      Gene Delivery.
AB  - Water-soluble conjugated polymers (WCPs) have prospective applications in the
      field of bioimaging, disease diagnosis, and therapy. However, the use of WCPs
      with controllability and regioregularity for bioapplications have scarcely been
      reported. In this work, we synthesized polythiophenes containing ester side
      chains (P3ET) via Kumada catalyst-transfer polycondensation (KCTP) and confirmed
      a quasi-"living" chain-growth mechanism. In addition, we obtained cationic
      regioregular polythiophenes (cPTs) by aminolysis of P3ET with varied chain
      lengths, and studied DNA binding capability and gene delivery performance.
      Benefiting from photocontrolled generation of intracellular reactive oxygen
      species (ROS), the cationic polythiophenes successfully delivered DNA into tumor
      cells without additional polymer species.

PMID- 29323478
TI  - Simultaneous Detection of Antibiotic Resistance Genes on Paper-Based Chip Using
      [Ru(phen)2dppz]2+ Turn-on Fluorescence Probe.
AB  - Antibiotic resistance, the ability of some bacteria to resist antibiotic drugs,
      has been a major global health burden due to the extensive use of antibiotic
      agents. Antibiotic resistance is encoded via particular genes; hence the specific
      detection of these genes is necessary for diagnosis and treatment of antibiotic
      resistant cases. Conventional methods for monitoring antibiotic resistance genes
      require the sample to be transported to a central laboratory for tedious and
      sophisticated tests, which is grueling and time-consuming. We developed a paper
      based chip, integrated with loop-mediated isothermal amplification (LAMP) and the
      "light switch" molecule [Ru(phen)2dppz]2+, to conduct turn-on fluorescent
      detection of antibiotic resistance genes. In this assay, the amplification
      reagents can be embedded into test spots of the chip in advance, thus simplifying
      the detection procedure. [Ru(phen)2dppz]2+ was applied to intercalate into
      amplicons for product analysis, enabling this assay to be operated in a wash-free
      format. The paper-based detection device exhibited a limit of detection (LOD) as
      few as 100 copies for antibiotic resistance genes. Meanwhile, it could detect
      antibiotic resistance genes from various bacteria. Noticeably, the approach can
      be applied to other genes besides antibiotic resistance genes by simply changing
      the LAMP primers. Therefore, this paper-based chip has the potential for point-of
      care (POC) applications to detect various gene samples, especially in resource
      limited conditions.

PMID- 29323479
TI  - Solution-Processed n-Type Graphene Doping for Cathode in Inverted Polymer Light
      Emitting Diodes.
AB  - n-Type doping with (4-(1,3-dimethyl-2,3-dihydro-1H-benzoimidazol-2-yl)phenyl)
      dimethylamine (N-DMBI) reduces a work function (WF) of graphene by ~0.45 eV
      without significant reduction of optical transmittance. Solution process of N
      DMBI on graphene provides effective n-type doping effect and air-stability at the
      same time. Although neutral N-DMBI act as an electron receptor leaving the
      graphene p-doped, radical N-DMBI acts as an electron donator leaving the graphene
      n-doped, which is demonstrated by density functional theory. We also verify the
      suitability of N-DMBI-doped n-type graphene for use as a cathode in inverted
      polymer light-emitting diodes (PLEDs) by using various analytical methods.
      Inverted PLEDs using a graphene cathode doped with N-DMBI radical showed
      dramatically improved device efficiency (~13.8 cd/A) than did inverted PLEDs with
      pristine graphene (~2.74 cd/A). N-DMBI-doped graphene can provide a practical way
      to produce graphene cathodes with low WF in various organic optoelectronics.

PMID- 29323480
TI  - Tailoring the Fluorescence of AIE-Active Metal-Organic Frameworks for Aqueous
      Sensing of Metal Ions.
AB  - A hydroxyl-functionalized ligand was designed for the construction of metal
      organic framework (MOF) materials with the aggregation-induced emission (AIE)
      feature, in which the fluorescence can be deliberately tailored: quenching the
      fluorescence to an "off" state by the decoration with heterocyclic auxiliary
      ligand 4,4'-bypyridine (Bpy) in the framework as a quenching agent and triggering
      the enhanced fluorescence to an "on" state by removal of Bpy through the metal
      competitive coordination substitution strategy. Our study shows that the
      occurrence of exciton migration between the AIE linker and conjugated auxiliary
      ligand Bpy causes fluorescence quenching. Time-dependent density functional
      theory was employed to understand the photoinduced electron transfer process and
      explain the origins of fluorescence quenching. Using this strategy, the prepared
      MOF material can perform as a fluorescence "off-on" probe for highly sensitive
      detection of Al3+ in aqueous media. The hydroxyl group plays a crucial role in
      sensing as it can selectively chelate Al3+, which is directly related to the
      dissociation of nonfluorescent MOF and consequent activation of the AIE process.

PMID- 29323481
TI  - New Mechanism of Extractive Electrospray Ionization Mass Spectrometry for
      Heterogeneous Solid Particles.
AB  - Real-time in situ mass spectrometry analysis of airborne particles is important
      in several applications, including exposure studies in ambient air, industrial
      settings, and assessing impacts on visibility and climate. However, obtaining
      molecular and 3D structural information is more challenging, especially for
      heterogeneous solid or semisolid particles. We report a study of extractive
      electrospray ionization mass spectrometry (EESI-MS) for the analysis of solid
      particles with an organic coating. The goal is to elucidate how much of the
      overall particle content is sampled, and determine the sensitivity of this
      technique to the surface layers. It is shown that, for NaNO3 particles coated
      with glutaric acid (GA), very little of the solid NaNO3 core is sampled compared
      to the GA coating, whereas for GA particles coated with malonic acid (MA),
      significant signals from both the MA coating and the GA core are observed.
      However, conventional ESI-MS of the same samples collected on a Teflon filter
      (and then extracted) detects much more core material compared to EESI-MS in both
      cases. These results show that, for the experimental conditions used here, EESI
      MS does not sample the entire particle but, instead, is more sensitive to surface
      layers. Separate experiments on single-component particles of NaNO3, GA, or
      citric acid show that there must be a kinetics limitation to dissolution that is
      important in determining EESI-MS sensitivity. We propose a new mechanism of EESI
      solvent droplet interaction with solid particles that is consistent with the
      experimental observations. In conjunction with previous EESI-MS studies of
      organic particles, these results suggest that EESI does not necessarily sample
      the entire particle when solid, and that not only solubility but also surface
      energies and the kinetics of dissolution play an important role.

PMID- 29323482
TI  - A Fluorine-free Slippery Surface with Hot Water Repellency and Improved Stability
      against Boiling.
AB  - Inspired by natural living things such as lotus leaves and pitcher plants,
      researchers have developed many excellent antifouling coatings. In particular,
      hot-water-repellent surfaces have received much attention in recent years because
      of their wide range of applications. However, coatings with stability against
      boiling in hot water have not been achieved yet. Long-chain perfluorinated
      materials, which are often used for liquid-repellent coatings owing to their low
      surface energy, hinder the potential application of antifouling coatings in food
      containers. Herein, we design a fluorine-free slippery surface that immobilizes a
      biocompatible lubricant layer on a phenyl-group-modified smooth solid surface
      through OH-pi interactions. The smooth base layer was fabricated by modification
      of phenyltriethoxysilane through a sol-gel method. The pi-electrons of the phenyl
      groups interact with the carboxyl group of the oleic acid used as a lubricant,
      which facilitates immobilization on the base layer. Water droplets slid off the
      surface in the temperature range from 20 to 80  degrees C at very low sliding
      angles (<2 degrees ). Furthermore, we increased the pi-electron density in the
      base layer to strengthen the OH-pi interactions, which improved long-term boiling
      stability under hot water. We believe that this surface will be applied in fields
      in which the practical use of antifouling coatings is desirable, such as food
      containers, drink cans, and glassware.

PMID- 29323483
TI  - Correction to Synthesis of Potent and Selective Inhibitors of Aldo-Keto Reductase
      1B10 and Their Efficacy against Proliferation, Metastasis, and Cisplatin
      Resistance of Lung Cancer Cells.

PMID- 29323484
TI  - Quaternary Layered Semiconductor Ba2Cr4GeSe10: Synthesis, Crystal Structure, and
      Thermoelectric Properties.
AB  - A quaternary narrow-band-gap semiconductor, Ba2Cr4GeSe10, has been discovered by
      solid-state reaction. It features a new structure type and crystallizes in the
      triclinic space group P1 (No. 2). The featured 2D anionic layers are constructed
      by condensed CrSe6 octahedra that are stacking along the c axis, with dispersed
      GeSe4 tetrahedra and located Ba2+ cations forming these layers. The energy-band
      structure shows a clear separation between the region of electronic conduction
      and the zone of electronic insulation. Significantly, an undoped Ba2Cr4GeSe10
      sample shows a desirable low thermal conductivity kappaT (0.51-0.87 W/m.K) and a
      high Seebeck coefficient S (351-404 MUV/K) and reaches a ZT ~ 0.08 at 773 K.

PMID- 29323485
TI  - Spark Plasma Sintering (SPS)-Assisted Synthesis and Thermoelectric
      Characterization of Magneli Phase V6O11.
AB  - The Magneli phase V6O11 was synthesized in gram amounts from a powder mixture of
      V6O11/V7O13 and vanadium metal, using the spark plasma sintering (SPS) technique.
      Its structure was determined with synchrotron X-ray powder diffraction data from
      a phase-pure sample synthesized by conventional solid-state synthesis. A special
      feature of Magneli-type oxides is a combination of crystallographic shear and
      intrinsic disorder that leads to relatively low lattice thermal conductivities.
      SPS prepared V6O11 has a relatively low thermal conductivity of kappa = 2.72 +/-
      0.06 W (m K)-1 while being a n-type conductor with an electrical conductivity of
      sigma = 0.039 +/- 0.005 (MUOmega m)-1, a Seebeck coefficient of alpha = -(35 +/-
      2) MUV K-1, which leads to a power factor of PF = 4.9 +/- 0.8 * 10-5W (m K2)-1 at
      ~600 K. Advances in the application of Magneli phases are mostly hindered by
      synthetic and processing challenges, especially when metastable and
      nanostructured materials such as V6O11 are involved. This study gives insight
      into the complications of SPS-assisted synthesis of complex oxide materials,
      provides new information about the thermal and electrical properties of vanadium
      oxides at high temperatures, and supports the concept of reducing the thermal
      conductivity of materials with structural building blocks such as
      crystallographic shear (CS) planes.

PMID- 29323487
TI  - Nanocoating of Hydrophobic Mesoporous Silica around MIL-101Cr for Enhanced
      Catalytic Activity and Stability.
AB  - The metal-organic framework (MOF) MIL-101Cr was readily encapsulated by a very
      thin shell (around 30 nm) of hydrophobic mesoporous silica, which replicates the
      irregular shape of the MOF nanocrystals. Such a silica shell facilitates the
      diffusion of hydrophobic reactants with enhancement of the catalytic activity of
      the MOF and significantly improved catalytic stability of the MOF in the
      oxidation of indene.

PMID- 29323486
TI  - A pH-Sensing Optode for Mapping Spatiotemporal Gradients in 3D Paper-Based Cell
      Cultures.
AB  - Paper-based cultures are an emerging platform for preparing 3D tissue-like
      structures. Chemical gradients can be imposed upon these cultures, generating
      microenvironments similar to those found in poorly vascularized tumors. There is
      increasing evidence that the tumor microenvironment is responsible for promoting
      drug resistance and increased invasiveness. Acidosis, or the acidification of the
      extracellular space, is particularly important in promoting these aggressive
      cancer phenotypes. To better understand how cells respond to acidosis there is a
      need for 3D culture platforms that not only model relevant disease states but
      also contain sensors capable of quantifying small molecules in the extracellular
      environment. In this work, we describe pH-sensing optodes that are capable of
      generating high spatial and temporal resolution maps of pH gradients in paper
      based cultures. This sensor was fabricated by suspending microparticles
      containing pH-sensitive (fluorescein) and pH-insensitive (diphenylanthracene)
      dyes in a polyurethane hydrogel, which was then coated onto a transparent film.
      The pH-sensing films have a fast response time, are reversible, stable in long
      term culture environments, have minimal photobleaching, and are not cytotoxic.
      These films have a pKa of 7.61 +/- 0.04 and are sensitive in the pH range
      corresponding to normal and tumorigenic tissues. With these optodes, we measured
      the spatiotemporal evolution of pH gradients in paper-based tumor models.

PMID- 29323488
TI  - Functional Implications of Intracellular Phase Transitions.
AB  - Intracellular environments are heterogeneous milieus comprised of macromolecules,
      osmolytes, and a range of assemblies that include membrane-bound organelles and
      membraneless biomolecular condensates. The latter are nonstoichiometric
      assemblies of protein and RNA molecules. They represent distinct phases and form
      via intracellular phase transitions. Here, we present insights from recent
      studies and provide a perspective on how phase transitions that lead to
      biomolecular condensates might contribute to cellular functions.

PMID- 29323489
TI  - Correction to "A Synthetically Tunable System To Control MLCT Excited-State
      Lifetimes and Spin States in Iron(II) Polypyridines".

PMID- 29323490
TI  - Activity-Related Microsecond Dynamics Revealed by Temperature-Jump Forster
      Resonance Energy Transfer Measurements on Thermophilic Alcohol Dehydrogenase.
AB  - Previous studies of a thermophilic alcohol dehydrogenase (ht-ADH) demonstrated a
      range of discontinuous transitions at 30  degrees C that include catalysis,
      kinetic isotope effects, protein hydrogen-deuterium exchange rates, and intrinsic
      fluorescence properties. Using the Forster resonance energy transfer response
      from a Trp-NADH donor-acceptor pair in T-jump studies of ht-ADH, we now report
      microsecond protein motions that can be directly related to active site
      chemistry. Two distinctive transients are observed: a slow, kinetic process
      lacking a temperature break, together with a faster transient that is only
      detectable above 30  degrees C. The latter establishes a link between enzyme
      activity and microsecond protein motions near the cofactor binding site, in a
      region distinct from a previously detected protein network that communicates with
      the substrate binding site. Though evidence of direct dynamical links between
      microsecond protein motions and active site bond cleavage events is extremely
      rare, these studies highlight the potential of T-jump measurements to uncover
      such properties.

PMID- 29323493
TI  - Luminescent Dinuclear Copper(I) Complexes as Potential Thermally Activated
      Delayed Fluorescence (TADF) Emitters: A Theoretical Study.
AB  - The excited state properties of a series of binuclear NHetPHOS-Cu(I) complexes
      (NHetPHOS) have been investigated by means of density functional theory (DFT) and
      time-dependent DFT (TD-DFT). It is shown that experimental trends observed in
      powder, generally explored via S1 and T1 excited state energetics and S1 <=> T1
      intersystem crossing (ISC) efficiency, are hardly analyzed on the basis of
      excited state properties calculated in solution. Indeed, several local minima
      corresponding to various structural deformations are evident on the lowest
      excited state potential energy surfaces (PES) when solvent correction is applied,
      leading to a four-state thermally activated delayed fluorescence (TADF)
      mechanism. In contrast, preliminary simulations performed in the solid point to
      the reduction of nuclear flexibility and consequently to a rather simple two
      state model.

PMID- 29323492
TI  - Total Synthesis of (+)-Pleuromutilin.
AB  - An 18-step synthesis of the antibiotic (+)-pleuromutilin is disclosed. The key
      steps of the synthesis include a highly stereoselective SmI2-mediated cyclization
      to establish the eight-membered ring and a stereospecific transannular [1,5]
      hydrogen atom transfer to set the C10 stereocenter. This strategy was also used
      to prepare (+)-12-epi-pleuromutilin. The chemistry described here will enable
      efforts to prepare new mutilin antibiotics.

PMID- 29323494
TI  - Iridium-Catalyzed Hydroarylation of Conjugated Dienes via pi-Allyliridium
      Intermediates.
AB  - A hydroxoiridium/cod complex efficiently catalyzed hydroarylation of conjugated
      dienes with arenes bearing an acidic N-H bond as a directing group, which can
      form an amidoiridium species as an active intermediate for C-H activation. A pi
      allyliridium(III) complex was isolated as a key intermediate leading to the
      addition product.

PMID- 29323491
TI  - G-Quadruplex Identification in the Genome of Protozoan Parasites Points to
      Naphthalene Diimide Ligands as New Antiparasitic Agents.
AB  - G-quadruplexes (G4) are DNA secondary structures that take part in the regulation
      of gene expression. Putative G4 forming sequences (PQS) have been reported in
      mammals, yeast, bacteria, and viruses. Here, we present PQS searches on the
      genomes of T. brucei, L. major, and P. falciparum. We found telomeric sequences
      and new PQS motifs. Biophysical experiments showed that EBR1, a 29 nucleotide
      long highly repeated PQS in T. brucei, forms a stable G4 structure. G4 ligands
      based on carbohydrate conjugated naphthalene diimides (carb-NDIs) that bind G4's
      including hTel could bind EBR1 with selectivity versus dsDNA. These ligands
      showed important antiparasitic activity. IC50 values were in the nanomolar range
      against T. brucei with high selectivity against MRC-5 human cells. Confocal
      microscopy confirmed these ligands localize in the nucleus and kinetoplast of T.
      brucei suggesting they can reach their potential G4 targets. Cytotoxicity and
      zebrafish toxicity studies revealed sugar conjugation reduces intrinsic toxicity
      of NDIs.

PMID- 29323495
TI  - Cascade Reaction of Isatins with 1,1-Enediamines: Synthesis of Multisubstituted
      Quinoline-4-carboxamides.
AB  - A one-step methodology for the synthesis of multisubstituted quinoline-4
      carboxamides was developed by simply refluxing a mixture of isatins 1 and various
      kinds of 1,1-enediamines 2-4 in a reaction catalyzed by NH2SO3H. As a result, a
      series of quinolone-4-carboxamides were produced through a novel cascade reaction
      mechanism. This reaction involved the formation of the quinoline ring accompanied
      by the formation of an amide bond in one step. Accordingly, this protocol is
      suitable for combinatorial and parallel syntheses of quinolone-4-carboxamide
      drugs or natural products.

PMID- 29323496
TI  - Direct Synthesis of Quinolines via Co(III)-Catalyzed and DMSO-Involved C-H
      Activation/Cyclization of Anilines with Alkynes.
AB  - A unique Co(III)-catalyzed and DMSO-involved C-H activation/cyclization of
      simple, cheap, and easily available anilines with alkynes for direct and highly
      efficient synthesis of privileged quinolines with exclusive regioselectivity and
      broad substrate/functional group tolerance and in good to excellent yields, where
      DMSO was employed as both the solvent and the C1 building block of quinoline
      products, is reported. Mechanistic experiments revealed that the versatile
      reaction might employ the 2-vinylbenzenamine species as the active intermediate.

PMID- 29323498
TI  - Scaling Laws in Directional Spreading of Droplets on Wettability-Confined
      Diverging Tracks.
AB  - Spontaneous pumpless transport of droplets on wettability-confined tracks is
      important for various applications, such as rapid transport and mixing of fluid
      droplets, enhanced dropwise condensation, biomedical devices, and so forth.
      Recent studies have shown that on an open surface, a superhydrophilic track of
      diverging width, laid on a superhydrophobic background, facilitates the transport
      of water from the narrower end to the wider end at unprecedented rates (up to 40
      cm/s) without external actuation. The spreading behavior on such surfaces,
      however, has only been characterized for water. Keeping in mind that such designs
      play a key role for a diverse range of applications, such as handling organic
      liquids and in point-of-care devices, the importance of characterizing the
      spreading behavior of viscous liquids on such surfaces cannot be overemphasized.
      In the present work, the spreading behavior on the aforementioned wettability
      patterned diverging tracks was observed for fluids of different viscosities. Two
      dimensionless variables were identified, and a comprehensive relationship was
      obtained. Three distinct temporal regimes of droplet spreading were established:
      I), a Washburn-type slow spreading, II) a much faster Laplace pressure-driven
      spreading, and III), a sluggish density-augmented Tanner-type film spreading. The
      results offer design guidance for tracks that can pumplessly manage fluids of
      various viscosities and surface tensions.

PMID- 29323497
TI  - Multifunnel Landscape of the Fold-Switching Protein RfaH-CTD.
AB  - Proteins such as the transcription factor RfaH can change biological function by
      switching between distinct three-dimensional folds. RfaH regulates transcription
      if the C-terminal domain folds into a double helix bundle and promotes
      translation when this domain assumes a beta-barrel form. This fold-switch has
      been also observed for the isolated C-terminal domain, dubbed by us as RfaH-C
      terminal domain (RfaH-CTD), and is studied here with a variant of the replica
      exchange-with-tunneling approach recently introduced by us. We use the enhanced
      sampling properties of this technique to map the free-energy landscape of RfaH
      CTD and to propose a mechanism for the conversion process.

PMID- 29323500
TI  - Interfacial Layering and Screening Behavior of Glyme-Based Lithium Electrolytes.
AB  - Understanding of electrical double layers is essential to all electrochemical
      devices, particularly at high charge carrier concentrations. Using a combined
      approach (surface force apparatus, zeta potential, infrared spectroscopy), we
      propose a model for the interfacial structure of triglyme electrolytes on
      muscovite mica. In contact with the pure triglyme, a brush-like polymeric
      structure grows on the mica surface. When lithium triflate is present in the
      triglyme, this structure is suppressed by anion adsorption and an extended double
      layer is formed. A surprising result of great fundamental significance is that
      the effective screening length measured by surface force apparatus at
      considerable lithium triflate concentrations (above 0.2 M) is substantially
      higher than expected from the Debye-Huckel theory. This suggests a high degree of
      complex salt association as a novel characteristic feature of salt-containing
      electrolytes.

PMID- 29323499
TI  - Nanometer Resolution Elemental Mapping in Graphene-Based TEM Liquid Cells.
AB  - We demonstrate a new design of graphene liquid cell consisting of a thin
      lithographically patterned hexagonal boron nitride crystal encapsulated on both
      sides with graphene windows. The ultrathin window liquid cells produced have
      precisely controlled volumes and thicknesses and are robust to repeated vacuum
      cycling. This technology enables exciting new opportunities for liquid cell
      studies, providing a reliable platform for high resolution transmission electron
      microscope imaging and spectral mapping. The presence of water was confirmed
      using electron energy loss spectroscopy (EELS) via the detection of the oxygen K
      edge and measuring the thickness of full and empty cells. We demonstrate the
      imaging capabilities of these liquid cells by tracking the dynamic motion and
      interactions of small metal nanoparticles with diameters of 0.5-5 nm. We further
      present an order of magnitude improvement in the analytical capabilities compared
      to previous liquid cell data with 1 nm spatial resolution elemental mapping
      achievable for liquid encapsulated bimetallic nanoparticles using energy
      dispersive X-ray spectroscopy (EDXS).

PMID- 29323501
TI  - The Pivotal Role of Copper in Neurodegeneration: A New Strategy for the Therapy
      of Neurodegenerative Disorders.
AB  - Copper is an essential trace element for the human body since it is a cofactor of
      several enzymes and proteins and plays a pivotal role in several biological
      functions (e.g., respiration, protection from oxidative damage, iron metabolism,
      etc.), also including the central nervous system development and functioning
      (e.g., synthesis of neurotransmitters, myelination, activation of neuropeptides,
      etc.). Therefore, copper dysmetabolism is associated with different toxic
      effects, mainly represented by oxidative stress, and it has been reported in many
      neurodegenerative disorders, such as Wilson's disease, Menkes disease,
      Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. This
      paper shows a detailed report of how copper is involved in the pathophysiology of
      these diseases. Moreover, a hint on novel therapeutic approaches based on
      restoring copper homeostasis through metal chelators will be pointed out.

PMID- 29323502
TI  - Regioselective Neighboring-Group-Participated 2,4-Dibromohydration of Conjugated
      Enynes: Synthesis of 2-(2,4-Dibromobut-2-enoyl)benzoate and Its Applications.
AB  - A regioselective 2,4-dibromohydration of conjugated enynes is reported for the
      synthesis of 2-(2,4-dibromobut-2-enoyl)benzoate. In the presence of tetra-n
      butylammonium bromide and H2O the transformation proceeds smoothly with good
      reaction efficiency and a broad reaction scope. Mechanism studies indicate that
      the neighboring ester group participates in the 2,4-dibromohydration, and the
      oxygen atom of ester is transferred into the C-C triple bond to form the keto
      carbonyl group in the product. 2-(2,4-Dibromobut-2-enoyl)benzoate is recognized
      as an important synthon toward phthalazin-1(2H)-one and the natural product
      Shihunine.

PMID- 29323503
TI  - Effective coping with supervisor conflict depends on control: Implications for
      work strains.
AB  - This study examined the interactive effects of interpersonal conflict at work,
      coping strategy, and perceived control specific to the conflict on employee work
      strain using multisource and time-lagged data across two samples. In Sample 1,
      multisource data was collected from 438 employees as well as data from
      participant-identified secondary sources (e.g., significant others, best
      friends). In Sample 2, time-lagged data from 100 full-time employees was
      collected in a constructive replication. Overall, findings suggested that the
      success of coping efforts as indicated by lower strains hinges on the combination
      of the severity of the stressor, perceived control over the stressor, and coping
      strategy used (problem-focused vs. emotion-focused coping). Results from the
      current study provide insights for why previous efforts to document the
      moderating effects of coping have been inconsistent, especially with regards to
      emotion-focused coping. (PsycINFO Database Record (c) 2018 APA, all rights
      reserved).

PMID- 29323504
TI  - Protective behavioral strategies mediate the relationship between behavioral
      economic risk factors and alcohol-related problems.
AB  - Behavioral economic measures of alcohol reward value and future orientation have
      received support as predictors of alcohol consumption, alcohol-related problems,
      and response to intervention. Protective behavioral strategies (PBS) have been
      shown to be a significant mediator between a variety of risk factors and alcohol
      related problems. The current article examines direct and mediating associations
      between measures of alcohol reward value (proportionate substance-related
      activity participation and enjoyment) and future orientation, use of PBS, and
      alcohol-related problems. Participants were 393 undergraduates (39.2% male, 78.9%
      Caucasian) who reported at least 2 past-month binge drinking episodes (5 and 4
      drinks for men and women, respectively). This study is a secondary analysis of
      data collected previously as part of a brief intervention study. Alcohol reward
      value and future orientation were significantly associated with both protective
      behavioral strategies and alcohol problems. PBS was a significant partial
      mediator between these variables and alcohol-related problems after controlling
      for gender, level of alcohol consumption, and sensation seeking. This study
      provides support for the hypothesis that high levels of reinforcement from
      alcohol relative to alternatives and low consideration of the future may lead to
      patterns of dysregulated drinking with few harm-reduction strategies that
      increase risk for alcohol problems. In addition to directly targeting PBS, brief
      alcohol interventions for college students should attempt to increase future
      orientation and substance-free activities. (PsycINFO Database Record

PMID- 29323506
TI  - Demand characteristics in episodic future thinking: Delay discounting and healthy
      eating.
AB  - Steep delay discounting, or rapid devaluation of future outcomes, is one
      mechanism that can account for the chronic selection of smaller-sooner over
      larger-later outcomes; that is, impulsive choice. Because steep delay discounting
      is correlated with maladaptive behavior, researchers have explored methods for
      reducing discounting. One empirically supported method is episodic future
      thinking (EFT), or vividly imagining one's future before completing the
      discounting task. However, EFT procedures may include demand characteristics,
      which could account for some its beneficial effects. In two experiments, demand
      characteristics were evaluated by having participants read a description of the
      interactions between a fictional experimenter and a human subject in a typical
      EFT study. When subsequently asked to indicate what the fictional experimenter
      expected the human subject to do after the EFT exercise, participants correctly
      deduced the experimenter's hypotheses: that EFT would reduce impulsive choice
      (Experiment 1A) and consumption of junk food (Experiment 1B). Future research
      should evaluate and control for the possibility that demand characteristics are
      at least partially responsible for the beneficial effects of EFT. (PsycINFO
      Database Record

PMID- 29323507
TI  - The Chains on All My People Are the Chains on Me: Restrictions to Collective
      Autonomy Undermine the Personal Autonomy and Psychological Well-Being of Group
      Members.
AB  - Four studies assessed the potentially detrimental effects that restrictions to
      collective autonomy (i.e., a group's freedom to determine and practice its own
      identity) may have for the personal autonomy and psychological well-being of
      group members. In Study 1, using 3 distinct samples (NSample1a = 123, NSample1b =
      129, NSample1c = 370), correlational and cross-cultural evidence indicates that
      perceived restrictions to the collective autonomy of one's group is directly
      associated with reduced personal autonomy, and indirectly associated with
      diminished well-being through personal autonomy. In Study 2 (N = 411), a
      longitudinal assessment of group members over 3 time-points during a 4-month
      period found that group members who perceived greater collective autonomy
      restriction also experienced reduced personal autonomy, and in turn, reduced
      psychological well-being over time. In Study 3 (N = 255), group members described
      a time during which their ingroup had (or did not have) its collective autonomy
      unduly restricted by other groups. Participants who were primed to think that
      their group lacked collective autonomy reported reduced feelings of personal
      autonomy, and reduced psychological well-being (compared with those primed to
      think their group had collective autonomy). In Study 4 (N = 389), collective
      autonomy was manipulated within the context of an intensive laboratory
      simulation. Collective autonomy-restricted group members experienced less
      personal autonomy than those who did not have their collective autonomy
      restricted. Together these findings suggest that restrictions to a group's
      collective autonomy may have detrimental consequences for the personal autonomy
      and psychological well-being of group members. (PsycINFO Database Record

PMID- 29323505
TI  - Effects of experimental pain induction on alcohol urge, intention to consume
      alcohol, and alcohol demand.
AB  - Research suggests one determinant of alcohol consumption may be physical pain,
      but there is no empirical evidence that pain has a causal effect on drinking.
      Therefore, the primary aim of this study was to test experimental pain as a
      determinant of several alcohol consumption proxies: self-reported urge to drink,
      intention to consume alcohol, and alcohol demand. This study also was designed to
      test negative affect as a mediator of the effects of pain on alcohol use proxies.
      We hypothesized that participants randomized to experimental pain induction (vs.
      no pain) would report greater urge, intention, and alcohol demand, and that these
      effects would be mediated by increased negative affect. Participants were healthy
      undergraduates who were moderate-heavy drinkers (N = 61). Experimental pain was
      induced using a novel capsaicin-heat model intended to approximate key features
      of clinical pain. Results indicated that participants in the pain condition
      subsequently endorsed greater urge and intention to drink. Furthermore, these
      effects were mediated by pain-induced negative affect. We observed no effect of
      pain on alcohol demand. This is the first study to demonstrate a causal effect of
      acute pain on urge and intention to drink. Given the close association between
      alcohol consumption, urge and intention to drink, these findings suggest that
      pain may influence alcohol consumption, which can have implications for
      individuals with co-occurring pain and alcohol use disorder (AUD). Specifically,
      individuals with co-occurring pain and AUD may drink to alleviate pain-related
      negative affect. Therefore, improving pain-coping skills may enhance pain
      management abilities, subsequently reducing coping-motivated drinking. (PsycINFO
      Database Record

PMID- 29323508
TI  - Past-focused temporal communication overcomes conservatives' resistance to
      liberal political ideas.
AB  - Nine studies and a meta-analysis test the role of past-focused temporal
      communication in reducing conservatives' disagreement with liberal political
      ideas. We propose that conservatives are more prone to warm, affectionate, and
      nostalgic feelings for past society. Therefore, they are more likely to support
      political ideas-including those expressing liberal values-that can be linked to a
      desirable past state (past focus), rather than a desirable future state (future
      focus) of society. Study 1 supports our prediction that political conservatives
      are more nostalgic for the past than liberals. Building on this association, we
      demonstrate that communicating liberal ideas with a past focus increases
      conservatives' support for leniency in criminal justice (Studies 2a and 2b), gun
      control (Study 3), immigration (Study 4), social diversity (Study 5), and social
      justice (Study 6). Communicating messages with a past focus reduced political
      disagreement (compared with a future focus) between liberals and conservatives by
      between 30 and 100% across studies. Studies 5 and 6 identify the mediating role
      of state and trait nostalgia, respectively. Study 7 shows that the temporal
      communication effect only occurs under peripheral (and not central) information
      processing. Study 8 shows that the effect is asymmetric; a future focus did not
      increase liberals' support for conservative ideas. A mixed-effects meta-analysis
      across all studies confirms that appealing to conservatives' nostalgia with a
      past-focused temporal focus increases support for liberal political messages
      (Study 9). A large portion of the political disagreement between conservatives
      and liberals appears to be disagreement over style, and not content of political
      issues. (PsycINFO Database Record

PMID- 29323509
TI  - Five Factor Model personality disorder scales: An introduction to a special
      section on assessment of maladaptive variants of the five factor model.
AB  - The Five-Factor Model (FFM) is a dimensional model of general personality
      structure, consisting of the domains of neuroticism (or emotional instability),
      extraversion versus introversion, openness (or unconventionality), agreeableness
      versus antagonism, and conscientiousness (or constraint). The FFM is arguably the
      most commonly researched dimensional model of general personality structure.
      However, a notable limitation of existing measures of the FFM has been a lack of
      coverage of its maladaptive variants. A series of self-report inventories has
      been developed to assess for the maladaptive personality traits that define
      Diagnostic and Statistical Manual of Mental Disorders (fifth edition; DSM-5)
      Section II personality disorders (American Psychiatric Association [APA], 2013)
      from the perspective of the FFM. In this paper, we provide an introduction to
      this Special Section, presenting the rationale and empirical support for these
      measures and placing them in the historical context of the recent revision to the
      APA diagnostic manual. This introduction is followed by 5 papers that provide
      further empirical support for these measures and address current issues within
      the personality assessment literature. (PsycINFO Database Record

PMID- 29323510
TI  - Consensual lay profiles of narcissism and their connection to the Five-Factor
      Narcissism Inventory.
AB  - Although there is evidence that experts agree on the traits that characterize
      narcissism, this agreement may be due, in part, to the influence of the
      operationalizations based on the American Psychiatric Association's series of
      Diagnostic and Statistical Manuals of Mental Disorders (American Psychiatric
      Association [APA], 1980, 1994, 2013). Because these trait descriptions are
      important in shaping conceptualizations and serving as empirical criteria for
      construct validation, we explored their generalizability. In Study 1, we
      collected lay ratings (N = 1,792) of prototypical cases of narcissism across 15
      different categories (e.g., gender, age, occupational status) on the 30 traits of
      the five-factor model (FFM). There was good agreement within and across rating
      categories and the trait profiles were quite similar to existing ratings made by
      academicians and clinicians. In Study 2 (N = 603), we examined the degree to
      which various scores from the Five-Factor Narcissism Inventory-Short Form (FFNI
      SF; Sherman et al., 2015) provided empirical matches to these FFM profiles (mean
      lay ratings from Study 1; existing expert-based and meta-analytically derived
      profiles). In general, scores from the FFNI-SF grandiose scale, as well as the
      empirically derived FFNI-SF Antagonism and Agentic Extraversion components
      yielded FFM profiles closely aligned to the various consensus profiles. These
      results are generally consistent with a burgeoning literature that suggests that
      the FFNI/FFNI-SF is a promising tool for the study of narcissism given its
      comprehensiveness, flexibility, and ties to the predominant model of personality.
      (PsycINFO Database Record

PMID- 29323511
TI  - Representing schizotypal thinking with dimensional traits: A case for the Five
      Factor Schizotypal Inventory.
AB  - Building on support for the five-factor model (FFM) of personality disorder, the
      Five Factor Schizotypal Inventory (FFSI) was developed to assess maladaptive
      traits relevant to schizotypal personality disorder. While the development of the
      FFSI supports a continuity between schizotypal thinking and perception (STAP) and
      the FFM domain of Openness to Experience, other studies show inconsistent
      findings concerning the strength of this relationship. The current study
      evaluates these relationships by investigating specific components of a short
      form of the FFSI (e.g., the FFSI-SF) and 2 other measures of maladaptive traits
      with the lower order components within commonly employed measures of Openness to
      Experience. Nomological network similarities were evaluated for the relation of
      these scales with a series of conceptually relevant variables including
      intelligence, creativity, and positive schizotypy in a sample of 403
      undergraduates, including 102 that were prescreened for elevated symptoms of
      schizotypal personality disorder (PD). These analyses revealed strong relations
      across the 3 measures of traits relevant to STAP, supporting the validity of the
      FFSI-SF. Most notably, 2 specific scales-Multidimensional Personality
      Questionnaire (MPQ) Absorption and Openness to Fantasy appeared to best capture
      the core variance across these measures. Furthermore, a nuanced pattern of
      relations suggested that specific components of STAP (e.g., oddity and fantasy
      proneness) matched closely with components of Openness to Experience. The results
      provide additional support for view that schizotypal thinking can be well
      captured by personality dimensions that run continuously across normal and
      pathological levels. (PsycINFO Database Record

PMID- 29323512
TI  - Informant assessment: The Informant Five-Factor Narcissism Inventory.
AB  - A series of self-report measures of personality disorder from the perspective of
      the five-factor model (FFM) have been published; however, no informant-report
      versions have been developed. An informant version of the Five Factor Narcissism
      Inventory (FFNI) is particularly apt, given the degree of distortion in self
      description inherent to narcissism. The present study provides initial validation
      for the Informant Five-Factor Narcissism Inventory (IFFNI). In Study 1, informant
      reports from friends, romantic partners, parents, and other family members were
      compared with self-reports provided by undergraduate college students on the
      IFFNI, FFM personality, and social dysfunction. Self-other agreement for IFFNI
      Grandiose (G) was higher than what has been found with other narcissism measures.
      No self-informant convergence, though, was found for IFFNI Vulnerable (V). From
      the informant view, IFFNI-G and V narcissism were associated with social
      dysfunction, whereas from the self-view only FFNI-V was associated with social
      dysfunction. In Study 2, grandiose and vulnerable narcissists, identified by
      participants recruited from MTurk, were described in terms of the IFFNI, FFM, and
      Pathological Narcissism Inventory (PNI). Results indicated that the IFFNI
      discriminated well between G and V narcissism for all but a few scales. The
      exceptions may reflect vulnerable narcissistic traits within grandiose
      narcissists. In comparison, the PNI obtained a very similar informant profile for
      the G and V narcissists. In sum, the results of the current study suggest value
      in having an informant-based measure of narcissism. (PsycINFO Database Record

PMID- 29323513
TI  - The Five Factor Borderline Inventory: Behavioral outcomes across time.
AB  - The Five-Factor Borderline Inventory Short Form (FFBI-SF) is a 48-item
      dimensional measure of borderline personality disorder (BPD) that was developed
      from the Five-factor model (FFM). Previous research has examined the
      relationships of the FFBI-SF to the FFM and BPD. The purpose of the current study
      was to investigate the relationship of FFBI-SF scales with behavioral outcomes,
      such as self-injury, physical fights, panic symptoms, promiscuous sex, theft,
      attempted suicide, reckless driving, and binge eating. A potential advantage of
      the FFBI-SF, relative to other measures of BPD, is the provision of subscales,
      which provides a more precise and differentiated assessment. In the current
      study, the predictive validity of the FFBI-SF in relation to various impulsive
      behaviors was investigated across a 2-month time period. Additional comparisons
      were also made with respect to a more traditional measure of borderline
      personality disorder and an assessment of the normal range of the FFM.
      Undergraduate students in psychology courses (T1 = 938, T2 = 284, T3 = 163) and
      workers from Amazon Mechanical Turk (T1 = 215, T2 = 167, T3 = 157) were
      administered personality measures and a measure of impulsive behaviors across 3
      time points. The results are discussed with respect to the comparative validity
      of the FFBI-SF, relative to traditional measures of borderline personality
      disorder and the FFM. Overall, the study provided evidence that the FFBI-SF is
      able to predict specific maladaptive behaviors over time and therefore may be
      useful in clinical and research settings. (PsycINFO Database Record

PMID- 29323514
TI  - FFMPD scales: Comparisons with the FFM, PID-5, and CAT-PD-SF.
AB  - A series of 8 Five Factor Model Personality Disorder (FFMPD) scales have been
      developed to assess, from the perspective of the Five Factor Model (FFM), the
      maladaptive traits included within DSM-5 Section II personality disorders. An
      extensive body of FFMPD research has accumulated. However, for the most part,
      each study has been confined to the scales within 1 particular FFMPD Inventory.
      The current study considered 36 FFMPD scales, at least 1 from each of the 8 FFMPD
      inventories, including 8 scales considered to be from neuroticism, 8 from
      extraversion, 5 from openness, 8 from agreeableness, and 7 from
      conscientiousness. Their convergent, discriminant, and structural relationship
      with the FFM was considered, and compared with the structural relationship with
      the FFM obtained by the Personality Inventory for DSM-5 (PID-5) and the
      Computerized Adaptive Test-Personality Disorder-Static Form (CAT-PD-SF). Support
      for an FFM structure was obtained (albeit with agreeableness defining 1 factor
      and antagonism a separate factor). Similarities and differences across the FFMPD,
      PID-5, and CAT-PD-SF scales were highlighted. (PsycINFO Database Record

PMID- 29323515
TI  - Suboptimal choice, reward-predictive signals, and temporal information.
AB  - Suboptimal choice refers to preference for an alternative offering a low
      probability of food (suboptimal alternative) over an alternative offering a
      higher probability of food (optimal alternative). Numerous studies have found
      that stimuli signaling probabilistic food play a critical role in the development
      and maintenance of suboptimal choice. However, there is still much debate about
      how to characterize how these stimuli influence suboptimal choice. There is
      substantial evidence that the temporal information conveyed by a food-predictive
      signal governs its function as both a Pavlovian conditioned stimulus and as an
      instrumental conditioned reinforcer. Thus, we explore the possibility that food
      predictive signals influence suboptimal choice via the temporal information they
      convey. Application of this temporal information-theoretic approach to suboptimal
      choice provides a formal, quantitative framework that describes how food
      predictive signals influence suboptimal choice in a manner consistent with
      related phenomena in Pavlovian conditioning and conditioned reinforcement. Our
      reanalysis of previous data on suboptimal choice suggests that, generally
      speaking, preference in the suboptimal choice procedure tracks relative temporal
      information conveyed by food-predictive signals for the suboptimal and optimal
      alternatives. The model suggests that suboptimal choice develops when the food
      predictive signal for the suboptimal alternative conveys more temporal
      information than that for the optimal alternative. Finally, incorporating a role
      for competition between temporal information provided by food-predictive signals
      and relative primary reinforcement rate provides a reasonable account of existing
      data on suboptimal choice. (PsycINFO Database Record

PMID- 29323516
TI  - The probability of reinforcement per trial affects posttrial responding and
      subsequent extinction but not within-trial responding.
AB  - During magazine approach conditioning, rats do not discriminate between a
      conditional stimulus (CS) that is consistently reinforced with food and a CS that
      is occasionally (partially) reinforced, as long as the CSs have the same overall
      reinforcement rate per second. This implies that rats are indifferent to the
      probability of reinforcement per trial. However, in the same rats, the per-trial
      reinforcement rate will affect subsequent extinction-responding extinguishes more
      rapidly for a CS that was consistently reinforced than for a partially reinforced
      CS. Here, we trained rats with consistently and partially reinforced CSs that
      were matched for overall reinforcement rate per second. We measured conditioned
      responding both during and immediately after the CSs. Differences in the per
      trial probability of reinforcement did not affect the acquisition of responding
      during the CS but did affect subsequent extinction of that responding, and also
      affected the post-CS response rates during conditioning. Indeed, CSs with the
      same probability of reinforcement per trial evoked the same amount of post-CS
      responding even when they differed in overall reinforcement rate and thus evoked
      different amounts of responding during the CS. We conclude that reinforcement
      rate per second controls rats' acquisition of responding during the CS, but at
      the same time, rats also learn specifically about the probability of
      reinforcement per trial. The latter learning affects the rats' expectation of
      reinforcement as an outcome of the trial, which influences their ability to
      detect retrospectively that an opportunity for reinforcement was missed, and, in
      turn, drives extinction. (PsycINFO Database Record

PMID- 29323517
TI  - Individual differences are more than a gene * environment interaction: The role
      of learning.
AB  - Individual differences in behavior are understood generally as arising from an
      interaction between genes and environment, omitting a crucial component. The
      literature on animal and human learning suggests the need to posit principles of
      learning to explain our differences. One of the challenges for the advancement of
      the field has been to establish how general principles of learning can explain
      the almost infinite variation in behavior. We present a case that: (a) individual
      differences in behavior emerge, in part, from principles of learning; (b)
      associations provide a descriptive mechanism for understanding the contribution
      of experience to behavior; and (c) learning theories explain dissociable aspects
      of behavior. We use 4 examples from the field of learning to illustrate the
      importance of involving psychology, and associative theory in particular, in the
      analysis of individual differences, these are (a) fear learning; (b) behavior
      directed to cues for outcomes (i.e., sign- and goal- tracking); (c) stimulus
      learning related to attention; and (d) human causal learning. (PsycINFO Database
      Record

PMID- 29323518
TI  - Variety overcomes the specificity of cue-potentiated feeding in rats.
AB  - Cue-potentiated feeding (CPF) describes the stimulation of food consumption by
      cues that have become associated with food. Determining under what Conditions CPF
      occurs is important to better understand how exposure to food cues contributes to
      overeating. CPF is typically found to be specific: cues enhance consumption only
      of the food they have signaled. Further, previous research has focused largely on
      discrete cues rather than multimodal cues such as a feeding environment. The
      present experiments paired a "Plus" context with highly palatable food and a
      "Minus" context with no food or chow in adult female rats. Experiment 1 confirmed
      that the Plus context enhanced consumption of the paired food (Froot Loops) but
      not a different food (banana bread). Experiments 2 and 3 tested whether pairing a
      variety of foods with the Plus context would overcome this specificity. In
      Experiment 2 the Plus context either contained bland chow (Chow group), 1 (Single
      group), or 3 palatable foods (Variety group). The test food, Froot Loops, was
      familiar but never paired with the Plus context. The Variety group exhibited CPF
      by eating more Froot Loops in the Plus than in the Minus context, while Single
      and Chow groups ate equivalently in the 2 contexts. Experiment 3 replicated this
      effect when the Minus context contained chow during training and when a novel
      food was tested. These findings have important implications for overeating given
      that modern food environments are typified by variety and that food consumption
      often occurs outside the home. (PsycINFO Database Record

PMID- 29323519
TI  - Pigeons in control of their actions: Learning and performance in stop-signal and
      change-signal tasks.
AB  - In human participants, 2 paradigms commonly assumed to measure the executive
      control processes involved in response inhibition are the stop-signal and change
      signal tasks. There is, however, also considerable evidence that performance in
      these tasks can be mediated by associative processes. To assess which components
      of inhibitory response control might be associative, we developed analogues of
      these tasks for pigeons. We trained pigeons to peck quickly at 1 of 2 keys of
      different colors to obtain a food reward. On some trials, the rewarded key was
      replaced (after a varying interval) by a signal of a different color. For some
      birds, this was a change signal: pecking the signal had no effect, but pecking
      the usually unrewarded alternative key led to a reward, so the response had to be
      changed. For other birds, the change in color was a stop signal: pecking the
      alternative key remained ineffective, but pecking the signal now led to a timeout
      instead of the usual reward, so responses had to be withheld. Pigeons succeeded
      in both tasks, but performance declined with increasing signal delay. The details
      of performance in both tasks were consistent with the independent horse-race
      model of inhibitory control often applied to studies of human participants. This
      outcome further suggests that stop-signal tasks of the kind used here might not
      necessarily be suitable for assessing top-down executive-control processes in
      humans. (PsycINFO Database Record

PMID- 29323520
TI  - Spectrum of embitterment manifestations.
AB  - OBJECTIVE: Embitterment is seen in reaction to injustice, vilification, or
      humiliation. Similar to anxiety, it is known to everybody, but it can also occur
      in the context of mental disorders and even become an illness in itself. The goal
      of the present study is to describe the spectrum of the types, rate, intensity,
      and clinical context of embitterment manifestations. METHOD: The posttraumatic
      embitterment disorder (PTED) self-rating scale was used to screen for reactive
      embitterment in 1,479 psychosomatic inpatients. Of these, 489 patients showed
      increased scores and were interviewed with a standardized diagnostic interview
      investigating embitterment and the life events that elicit it. RESULTS: Feelings
      of embitterment, irrespective of intensity, were known to 86.5% of the sample and
      associated with impairment in daily life. Four different types of patients could
      be identified: (a) nonreactive embitterment or embitterment-prone personality
      (i.e., increased embitterment without reports about specific negative life
      events), (b) complex embitterment (i.e., increased embitterment in the context of
      multiple negative life events), (c) PTED in reaction to a single traumatic event,
      and (d) secondary embitterment (i.e., increased embitterment in the context of
      other mental disorders). CONCLUSIONS: Embitterment is part of the normal spectrum
      of emotions, but it is also relevant in mental disorders. Increased embitterment
      can be part of other mental illnesses, such as personality disorders, but it also
      constitutes a state of illness in itself in the form of embitterment-prone
      personality, PTED, or complex PTED. (PsycINFO Database Record

PMID- 29323521
TI  - Psychological processes in chronic embitterment: The potential contribution of
      rumination.
AB  - OBJECTIVE: Chronic embitterment has received considerable attention in terms of
      its presentation and epidemiology, but there has been relatively little focus on
      its psychology. The present study aimed to test the hypothesis that embitterment
      is positively correlated with rumination, and that this effect is influenced by
      positive beliefs about rumination. METHOD: A convenience sample (N = 79) of staff
      of a health care facility attending its occupational health service completed
      questionnaires assessing chronic embitterment, work-related rumination
      (distinguishing affective rumination and problem solving pondering), positive
      beliefs about rumination, and depression. RESULTS: Embitterment scores correlated
      positively with affective rumination and depression. Positive beliefs about
      rumination correlated positively with problem-solving pondering but not with
      affective rumination. Regression analysis revealed that affective rumination
      contributed to embitterment independently of depression. CONCLUSIONS: Previous
      research has demonstrated that rumination impairs executive functions and problem
      solving. The association of affective rumination with embitterment may contribute
      to the explanation for why embitterment becomes chronic and is often difficult to
      alleviate. However, this association also opens up possibilities of intervention,
      in light of research evidence of the effectiveness of rumination-focused
      therapies. (PsycINFO Database Record

PMID- 29323522
TI  - Demoralization and embitterment.
AB  - OBJECTIVE: Individuals may experience a wide range of psychological reactions in
      response to negative life events. Even if events that threaten life have been
      always played a central role in research, recent studies have outlined that
      experiences, considered exceptional but part of the human existence (e.g.,
      divorce, unemployment, or chronic illness) may also lead individuals to
      experience enduring emotional states of suffering. Demoralization has been
      substantially described as an important condition occurring in response to
      stressful events, while a recent interest is growing on embitterment as a common
      reaction. METHOD: By analyzing the most relevant studies (MEDLINE, EMBASE,
      PsycLit, and Cochrane Library), this article discusses the main features of
      embitterment and demoralization, summarizing the similarities as well as the
      differences detectable between the 2 constructs. RESULTS: Some authors have
      described these phenomena as spectrum or gradients that start with normal human
      responses until getting to pathological conditions, characterized by prolonged
      intense psychological distress in relation to stressful events. Both have shown
      distinct psychopathological features than other stress-related mental disorders
      and have been recognized as predictors of negative outcomes, such as impairment
      in work and social functioning, reduction of quality of life, risk for mental and
      physical disorders, and suicidality. CONCLUSIONS: Demoralization and embitterment
      are multidimensional phenomena, connected to each other by bridge dimensions and
      in the meanwhile characterized by distinct features. Accurately exploring these
      clinical conditions is an ongoing challenge to clinicians and researchers, who
      are called for improving their recognition and proper therapeutic interventions
      that can ameliorate patients quality of life. (PsycINFO Database Record

PMID- 29323523
TI  - Trauma across generations and paths to adaptation and resilience.
AB  - OBJECTIVE: There is a growing literature on the intergenerational transmission of
      trauma, representing approaches across psychodynamic, family systems,
      epidemiological, sociological, and biological levels of analysis. Embitterment
      has been proposed as a response to severe, but normative, stressful events,
      different from the life-threatening trauma that precedes posttraumatic stress
      disorder (PTSD). METHOD: This article reviews the potential applicability of the
      construct of embitterment to trauma and intergenerational effects through (a) a
      historical review of the intergenerational transmission of trauma literature, (b)
      a discussion of embitterment versus PTSD, (c) a brief review of theories of
      mechanisms of transmission, and (d) a discussion of biological findings and their
      interpretation. RESULTS: Mechanisms of intergenerational transmission of trauma,
      which may include psychodynamic processes, vicarious trauma, learning and
      modeling, parenting and family environment, and biological influences, are
      reviewed. Survivor coping and resilience, and specifically the presence of PTSD,
      has emerged as an important moderator of parental trauma effects on the second
      generation. A table comparing posttraumatic embitterment disorder and PTSD is
      provided. CONCLUSION: The discussion emphasizes the importance of construing
      biological findings as flexible adaptations to stressors rather than
      deterministic indicators of damage, the relevance of context in interpreting such
      findings, and the role of community-level processes for healing. (PsycINFO
      Database Record

PMID- 29323524
TI  - Work disability in soldiers with posttraumatic stress disorder, posttraumatic
      embitterment disorder, and not-event-related common mental disorders.
AB  - OBJECTIVE: Posttraumatic mental disorders may occur with different affect
      qualities. Best known is posttraumatic stress disorder (PTSD), a conditioned
      anxiety reaction with intrusions. Another event-related mental disorder is
      posttraumatic embitterment (PTED), characterized by affect of embitterment and
      thoughts of revenge, occurring after an event deeply hurting basic beliefs.
      Knowing about associated disability is important for treatment and sociomedical
      decisions. This is the first study to explore work-disability in patients with
      PTSD, PTED, and not-event-related common mental disorder (CMD). METHOD: In this
      observational study, 101 soldiers (85% men, 31 years, 50% experienced expedition
      abroad) with different mental disorders were investigated concerning common
      mental disorders (MINI) and accompanying work capacity impairment (Mini-ICF-APP).
      Interviews were conducted by a state-licensed psychotherapist with expertise in
      sociomedical description of (work) capacity impairment. Patients with PTSD, PTED,
      and other CMD were compared concerning their degrees and pattern of work capacity
      impairment. RESULTS: PTSD patients (n = 23) were more strongly impaired in
      mobility as compared to patients with other CMD (n = 64) or PTED. Patients with
      PTED (n = 14) were more impaired in interactional capacities (contacts with
      others, group integration) as compared to patients with other CMD or PTSD.
      CONCLUSIONS: PTSD patients need support to improve mobility in (work-relevant)
      traffic situations. Apart from this, they are not specifically more or less
      impaired than patients with other CMD. PTED patients should get attention
      concerning their interactional problems as these may disturb esprit de corps,
      which is an essential requirement for service in the armed forces. (PsycINFO
      Database Record

PMID- 29323525
TI  - Embitterment and bereavement: The Sewol ferry accident example.
AB  - OBJECTIVE: On Wednesday, April 16, 2014, 261 high school students on a field trip
      died in the sinking of the Sewol ferry. The bereaved family of the Sewol ferry
      accident experienced one of the most painful traumatic losses such as the sudden
      death of one's child through an accident. This article reviewed and discussed
      embitterment related to traumatic loss through the example of the Sewol ferry
      accident. METHOD: Embitterment-related issues and problems in coping with the
      accident that is caused by societal factors were described. In addition,
      embitterment-related findings of several previous studies based on bereaved
      families' mental health cohort study were reviewed. RESULTS: Traumatic loss of
      the human-made ferry accident was accompanied with feelings of being cheated,
      injustice, incompetence, wrongdoing by a perpetrator, and the destruction of
      one's belief and value system, causing severe embitterment. Embitterment was
      related to other mental health problems including depression, anxiety, and
      complicated grief. CONCLUSION: Social support and positive individual resource
      including optimism and wisdom can be helpful for recovery from posttraumatic
      embitterment. The goal of grief is to remember the decedent, understand the
      changes created by the loss, and determine how to reinvest in life. Embitterment
      may disturb the process of grief. Without the management of the embitterment,
      true grief may not be possible. The breakdown of value systems and severe
      embitterment should get more attention in future research. (PsycINFO Database
      Record

PMID- 29323526
TI  - Psychological and neural correlates of embitterment in old age.
AB  - OBJECTIVE: Posttraumatic embitterment disorder (PTED) comprises a stress-related
      response to a negative life event that violates the belief system of the
      individual. Characteristic symptoms involve repeated intrusive thoughts,
      emotional arousal when reminded of the event, and decreases in well-being.
      METHOD: Within the scope of the present study, embitterment was treated as a
      continuous rather than categorical concept, and we investigated its psychological
      and brain structural correlates in a sample of healthy older adults. RESULTS: We
      found a negative association between the PTED self-rating score and self-reported
      well-being, life satisfaction, and future time perspective and a positive
      association with loneliness, perceived stress, chronic strain, and external
      control beliefs. We found no significant association between embitterment and
      brain regions that have been associated with stress exposure and posttraumatic
      stress disorder (PTSD)-hippocampus and the medial prefrontal cortex. This may
      emphasize the fundamental difference between PTED and PTSD. In a whole-brain
      analysis, we found a positive correlation between embitterment and gray matter
      volume in the precuneus and white matter volume in the bilateral uncinate
      fasciculus. CONCLUSIONS: The precuneus and uncinate fasciculus are brain regions
      that have been related to episodic memory retrieval, matching well to the
      symptoms of intrusive thoughts and an overwhelming preoccupation with the event
      that caused the PTED. Further longitudinal research is needed to unravel whether
      these structural correlates represent preconditions or rather the consequence of
      embitterment. (PsycINFO Database Record

PMID- 29323527
TI  - PDTRT special section: Methodological issues in personality disorder research.
AB  - Provides an introduction to the ongoing Special Section of Personality Disorders:
      Theory, Research, and Treatment. This special section is concerned with
      methodological issues in personality disorder research. This fourth edition of
      this series includes two articles which should be excellent resources for future
      research and manuscripts submitted to this journal. (PsycINFO Database Record

PMID- 29323528
TI  - Current directions in laboratory studies of personality pathology: Examples from
      borderline personality disorder, psychopathy, and schizotypy.
AB  - Much of the earliest research on personality pathology was observational and
      descriptive in nature, drawing heavily on subjective self-reports, however, the
      last 20 years have seen a surge of interest in laboratory-based studies.
      Laboratory research offers a number of benefits for researchers interested in
      personality disorders and personality pathology including the opportunities to
      use objective performance-based and behavioral measures, reveal the
      neuropsychological and biobehavioral processes that may help shape the experience
      and behavior of individuals with personality disorders, and create experimental
      designs that allow researchers to systematically explore the effect of context on
      emotional, behavioral and cognitive responding. Along with these benefits,
      laboratory research on personality disorders has its share of methodological and
      interpretive challenges and raise several key questions, including (a) How should
      we interpret findings that diverge from theory-driven predictions? (b) How do we
      reconcile discrepant results from subjective and performance-based assessments?
      and (c) Are these discrepancies due to methodological artifact, a hallmark of the
      disorder, or cause for theoretical reconsideration? The goal of this article is
      to review studies aimed at answering a key research question in the domains of
      borderline personality disorder, psychopathy, and schizotypy. Our review
      highlights significant progress in laboratory research on personality disorders,
      and identifies challenges that must be addressed to capitalize on the promise of
      laboratory methods. It is our hope that future experimental work proceeds with an
      eye toward theoretical coherence, methodological rigor, ecological validity, and
      clinical utility. (PsycINFO Database Record

PMID- 29323529
TI  - Applying causal mediation analysis to personality disorder research.
AB  - This article is designed to address fundamental issues in the application of
      causal mediation analysis to research on personality disorders. Causal mediation
      analysis is used to identify mechanisms of effect by testing variables as
      putative links between the independent and dependent variables. As such, it would
      appear to have relevance to personality disorder research. It is argued that
      proper implementation of causal mediation analysis requires that investigators
      take several factors into account. These factors are discussed under 5 headings:
      variable selection, model specification, significance evaluation, effect size
      estimation, and sensitivity testing. First, care must be taken when selecting the
      independent, dependent, mediator, and control variables for a mediation analysis.
      Some variables make better mediators than others and all variables should be
      based on reasonably reliable indicators. Second, the mediation model needs to be
      properly specified. This requires that the data for the analysis be prospectively
      or historically ordered and possess proper causal direction. Third, it is
      imperative that the significance of the identified pathways be established,
      preferably with a nonparametric bootstrap resampling approach. Fourth, effect
      size estimates should be computed or competing pathways compared. Finally,
      investigators employing the mediation method are advised to perform a sensitivity
      analysis. Additional topics covered in this article include parallel and serial
      multiple mediation designs, moderation, and the relationship between mediation
      and moderation. (PsycINFO Database Record

PMID- 29323530
TI  - Prevalence and Molecular Characterization of Antimicrobial Resistance in
      Escherichia coli Isolated from Raw Milk and Raw Milk Cheese in Egypt.
AB  - The goal of this study was to examine antimicrobial resistance and characterize
      the implicated genes in 222 isolates of Escherichia coli from 187 samples of raw
      milk and the two most popular cheeses in Egypt. E. coli isolates were tested for
      susceptibility to 12 antimicrobials by a disk diffusion method. Among the 222 E.
      coli isolates, 66 (29.7%) were resistant to one or more antimicrobials, and half
      of these resistant isolates showed a multidrug resistance phenotype (resistance
      to at least three different drug classes). The resistance traits were observed to
      tetracycline (27.5%), ampicillin (18.9%), streptomycin (18.5%), sulfamethoxazole
      trimethoprim (11.3%), cefotaxime (4.5%), kanamycin (4.1%), ceftazidime (3.6%),
      chloramphenicol (2.3%), nalidixic acid (1.8%), and ciprofloxacin (1.4%). No
      resistance to fosfomycin and imipenem was observed. Tetracycline resistance genes
      tetA, tetB, and tetD were detected in 53 isolates, 9 isolates, and 1 isolate,
      respectively, but tetC was not detected. Aminoglycoside resistance genes strA,
      strB, aadA, and aphA1 were detected in 41, 41, 11, and 9 isolates, respectively.
      Sulfonamide resistance genes sul1, sul2, and sul3 were detected in 7, 25, and 3
      isolates, respectively. Of 42 ampicillin-resistant isolates, blaTEM, blaCTX-M,
      and blaSHV were detected in 40, 9, and 3 isolates, respectively, and 10 (23.8%)
      ampicillin-resistant isolates were found to produce extended-spectrum beta
      lactamase. Each bla gene of extended-spectrum beta-lactamase-producing E. coli
      was further subtyped to be blaCTX-M-15, blaCTX-M-104, blaTEM-1, and blaSHV-12.
      The class 1 integron was also detected in 28 resistant isolates, and three
      different patterns were obtained by PCR-restriction fragment length polymorphism.
      Sequencing analysis of the variable region revealed that four isolates had
      dfrA12/orfF/aadA2, two had aadA22, and one had dfrA1/aadA1. These data suggest
      that antimicrobial-resistant E. coli are widely distributed in the milk
      production and processing environment in Egypt and may play a role in
      dissemination of antimicrobial resistance to other pathogenic and commensal
      bacteria.

PMID- 29323531
TI  - An Efficient Gas Chromatography-Mass Spectrometry Approach for the Simultaneous
      Analysis of Deoxynivalenol and Its Bacterial Metabolites 3-keto-DON and 3- epi
      DON.
AB  - Deoxynivalenol (DON) is one of the major toxic secondary metabolites produced by
      Fusarium fungi in cereal grains. Among the many promising strategies of DON
      detoxification are the microbial and enzymatic ones, which transform DON to
      nontoxic DON metabolites. Thus, proper analytical methods are needed for those
      DON metabolites. In this study, a robust gas chromatography-mass spectrometry (GC
      MS) procedure was developed and validated for the simultaneous analysis of DON
      and two of its bacterial metabolites, 3-keto-DON and 3- epi-DON. The procedure
      involves a straightforward vacuum drying and derivatization step before the
      subsequent GC-MS analysis. Following the optimized protocol, DON and these two
      metabolites were separated on a capillary column within 15 min. The linear ranges
      for the these compounds were 10 to 2,000 ng mL-1 with correlation coefficients
      >0.99. For DON, 3- epi-DON, and 3-keto-DON, the limits of detection were 0.8,
      3.0, and 0.05 ng mL-1, and the limits of quantification were 2.6, 10.0, and 1.0
      ng mL-1, respectively. For all three compounds, the obtained relative standard
      deviation was 1.2 to 5.5%, and the recovery rates were 89.5 to 103.6%. The
      developed method was further validated by analyzing DON metabolites resulting
      from the biotransformation of DON initiated by cell-free lysates of the bacterium
      Devosia mutans 17-2-E-8. The developed protocol was sensitive, precise, accurate,
      and robust for the determination of DON, 3- epi-DON, and 3-keto-DON in liquid
      media and potentially other complex matrices without interference from other
      compounds.

PMID- 29323532
TI  - Identification of CDK2 as a novel target in treatment of prostate cancer.
AB  - AIM: This study aims the potential gene involved in the metastasis of prostate
      cancer (Pca). METHODS: PubMed GEO datasets (GSE6605 and GSE6606) were downloaded.
      We used multiple bioinformatics methods to screen differentially expressed genes
      in Pca. Gene network was built by STRING and visualized by Cytoscape. All of the
      hub genes were analyzed by cBioPortal. Inhibition of CDK2 including siRNA,
      inhibitor and cas9-induced CDK2 knockout was followed by an invasion assay.
      Downstream genes of CDK2 were analyzed by western blot. RESULTS: Sequencing data
      were analyzed to screen the genes with expression alterations. The top genes were
      validated in our samples. 11 hub genes were screened out. Among these genes,
      STAT3 and CDK2 were significantly associated with recurrence. Further study
      suggested that inhibition of CDK2 reduced invasion of Pca cell lines. The
      invasion ability was rescued after reintroduction of CDK2. CONCLUSION: These data
      indicated that CDK2 was a crucial factor in metastasis of Pca and might be a
      novel therapy target. [Formula: see text].

PMID- 29323533
TI  - Comparison of repair characteristics of artificial dermis composite tissue with
      traditional prefabricated flap.
AB  - BACKGROUND: We compared the application of artificial dermis composite tissue and
      the traditional prefabricated flap in a rat model of an exposed bone and tendon
      injury. METHODS: Sprague Dawley rats were randomly divided into two groups (A and
      B, n = 40). Group A rats received artificial dermis composite tissue flaps while
      group B rats received traditional prefabricated flaps. Flap appearance, range of
      motion, degree of swelling, tissue histology, and imaging were compared between
      groups at 7, 14, 21, and 28 days. RESULTS: There was no difference in flap
      appearance, range of motion, and degree of swelling between groups. However,
      blood perfusion of the artificial dermis composite tissue flap was better than in
      the traditional prefabricated flap; artificial dermis was also found to be
      thicker than the traditional prefabricated flap. CONCLUSIONS: The artificial
      dermis composite tissue flap is an ideal method for repairing exposed bone and
      tendon, and displays a comparable repair effects and that it may be a better
      alternative compared with the traditional prefabricated flap.

PMID- 29323534
TI  - Healthy foods prepared at home: Diet and support as protective strategies during
      pregnancy for Hispanic women.
AB  - Birth outcomes tend to be better among Hispanics than among other ethnic groups,
      even when matched for poverty and education, and foreign-born Latinas compared to
      their US-born counterparts. These patterns suggest that sociocultural factors
      exhibited by recent immigrants have the potential to protect birth outcomes
      against the instability of minority and low socioeconomic status. To discover
      potential sociocultural factors, a pilot qualitative study was carried out in
      Tucson, Arizona, with 18 Hispanic mothers. The two most prevalent factors
      reported were (1) a healthy diet prepared at home from minimally processed
      ingredients, and (2) constant and comprehensive social support. When comparing
      responses related to diet by interview language preference, a proxy for
      acculturation, there was very little difference between participants who
      interviewed in Spanish and those who interviewed in English. This result may be
      explained by greater maternal social support and higher education levels among
      those who interviewed in English.

PMID- 29323535
TI  - Testing Process Factor Analysis Models Using the Parametric Bootstrap.
AB  - Process factor analysis (PFA) is a latent variable model for intensive
      longitudinal data. It combines P-technique factor analysis and time series
      analysis. The goodness-of-fit test in PFA is currently unavailable. In the paper,
      we propose a parametric bootstrap method for assessing model fit in PFA. We
      illustrate the test with an empirical data set in which 22 participants rated
      their effects everyday over a period of 90 days. We also explore Type I error and
      power of the parametric bootstrap test with simulated data.

PMID- 29323537
TI  - Investigational therapies targeting CD37 for the treatment of B-cell lymphoid
      malignancies.
AB  - INTRODUCTION: While chemotherapy still remains a cornerstone of oncologic
      therapy, immunotherapy with monoclonal antibodies has steadily improved the
      treatment strategy for several hematologic malignancies. New treatment options
      need to be developed for relapsed and refractory non-Hodgkin lymphoma (NHL)
      patients. Currently, novel agents targeting specific molecules on the surface of
      lymphoma cells, such as anti-CD37 antibodies, are under considerable
      investigation. Here we report on anti-CD37 targeting for the treatment of
      patients with B-cell NHL. Areas covered: CD37 seems to be the perfect therapeutic
      target in patients with NHL. The CD37 antigen is abundantly expressed in B-cells,
      but is absent on normal stem cells and plasma cells. It is hoped that anti-CD37
      monoclonal antibodies will increase the efficacy and reduce toxicity in patients
      with both newly diagnosed and relapsed and refractory disease. Recent clinical
      trials have shown promising outcomes for these agents, administered both as
      monotherapy and in combination with standard chemotherapeutics. Expert opinion:
      The development of new therapeutic options might help to avoid cytotoxic
      chemotherapy entirely in some clinical settings. This article presents the latest
      state of the art on the new treatment strategies in NHL patients. It also
      discusses recently approved agents and available clinical trial data.

PMID- 29323536
TI  - High Positive End-Expiratory Pressure Renders Spontaneous Effort Noninjurious.
AB  - RATIONALE: In acute respiratory distress syndrome (ARDS), atelectatic solid-like
      lung tissue impairs transmission of negative swings in pleural pressure (Ppl)
      that result from diaphragmatic contraction. The localization of more negative Ppl
      proportionally increases dependent lung stretch by drawing gas either from other
      lung regions (e.g., nondependent lung [pendelluft]) or from the ventilator.
      Lowering the level of spontaneous effort and/or converting solid-like to fluid
      like lung might render spontaneous effort noninjurious. OBJECTIVES: To determine
      whether spontaneous effort increases dependent lung injury, and whether such
      injury would be reduced by recruiting atelectatic solid-like lung with positive
      end-expiratory pressure (PEEP). METHODS: Established models of severe ARDS
      (rabbit, pig) were used. Regional histology (rabbit), inflammation (positron
      emission tomography; pig), regional inspiratory Ppl (intrabronchial balloon
      manometry), and stretch (electrical impedance tomography; pig) were measured.
      Respiratory drive was evaluated in 11 patients with ARDS. MEASUREMENTS AND MAIN
      RESULTS: Although injury during muscle paralysis was predominantly in
      nondependent and middle lung regions at low (vs. high) PEEP, strong inspiratory
      effort increased injury (indicated by positron emission tomography and histology)
      in dependent lung. Stronger effort (vs. muscle paralysis) caused local
      overstretch and greater tidal recruitment in dependent lung, where more negative
      Ppl was localized and greater stretch was generated. In contrast, high PEEP
      minimized lung injury by more uniformly distributing negative Ppl, and lowering
      the magnitude of spontaneous effort (i.e., deflection in esophageal pressure
      observed in rabbits, pigs, and patients). CONCLUSIONS: Strong effort increased
      dependent lung injury, where higher local lung stress and stretch was generated;
      effort-dependent lung injury was minimized by high PEEP in severe ARDS, which may
      offset need for paralysis.

PMID- 29323539
TI  - An Introduction to Kristof's Theorem for Solving Least-Square Optimization
      Problems Without Calculus.
AB  - Kristof's Theorem (Kristof, 1970 ) describes a matrix trace inequality that can
      be used to solve a wide-class of least-square optimization problems without
      calculus. Considering its generality, it is surprising that Kristof's Theorem is
      rarely used in statistics and psychometric applications. The underutilization of
      this method likely stems, in part, from the mathematical complexity of Kristof's
      ( 1964 , 1970 ) writings. In this article, I describe the underlying logic of
      Kristof's Theorem in simple terms by reviewing four key mathematical ideas that
      are used in the theorem's proof. I then show how Kristof's Theorem can be used to
      provide novel derivations to two cognate models from statistics and
      psychometrics. This tutorial includes a glossary of technical terms and an online
      supplement with R (R Core Team, 2017 ) code to perform the calculations described
      in the text.

PMID- 29323538
TI  - Clinical characteristics and outcomes of traditional Chinese medicine-induced
      liver injury: a systematic review.
AB  - BACKGROUNDS: Traditional Chinese medicine (TCM) is becoming increasingly popular
      and related adverse events are often ignored or underestimated. AIMS: This
      systematic review aimed to evaluate the clinical characteristics and outcomes of
      TCM-induced liver injury (TCM-ILI) and to estimate the proportion of TCM-ILI in
      all drug-induced liver injuries (DILI). METHODS: China National Knowledge
      Infrastructure, Wanfang, VIP, PubMed, and Embase databases were searched.
      Demographic, clinical, and survival data were extracted and pooled. Factors
      associated with worse outcomes were calculated. For the proportion meta-analyses,
      the data were pooled by using a random-effects model. RESULTS: Overall, 21,027
      articles were retrieved, of which 625 were finally included. There was a
      predominance of female and older patients. The proportion of liver
      transplantation was 2.18% (7/321). The mortality was 4.67% (15/321). Male, higher
      aspartate aminotransferase and direct bilirubin, and lower albumin were
      significantly associated with an increased risk of death/liver transplantation in
      TCM-ILI patients. The proportion of TCM-ILI in all DILI was 25.71%. The
      proportion was gradually increased with year. CONCLUSIONS: Our work summarises
      current knowledge regarding clinical presentation, disease course, and prognosis
      of TCM-ILI. TCM can result in hepatotoxicity, even death or necessitate life
      saving liver transplantation. Governmental regulation of TCM products should be
      strictly established.

PMID- 29323540
TI  - Poisoning by non-edible squash: retrospective series of 353 patients from French
      Poison Control Centers.
AB  - CONTEXT: Among the numerous varieties of squash that exist, some are edible while
      other bitter-tasting ones are not fit for human consumption. Cases of confusion
      seem to be multiplying and are characterized by digestive problems (diarrhea,
      vomiting, and abdominal pain). METHODS: This is a descriptive retrospective study
      of cases of exposure reported to French Poison Control Centers between 1 January
      2012 and 12 December 2016. RESULTS: 353 patients were included, with 71.7%
      belonging to collective cases of poisoning. The male to female sex ratio was 0.75
      for an average age of 38.2 +/- 23.6 years. The circumstances of exposure were
      dietary for 337 patients (95.5%). The majority of the squash consumed was
      purchased at a store (55.8%) but some also came from the garden (25.5%). 204
      patients (57.8%) mostly presented with diarrhea, vomiting, abdominal pain,
      sometimes with the consequent dehydration, hypotension, tachycardia, headaches,
      or vertigo. There were no deaths or severe (Poisoning Severity Score (PSS) 3)
      cases, but there were 14 patients (4.0%) of moderate severity, 190 patients
      (53.8%) of minor severity (PSS 1), and 149 patients (42.2%) without severity (PSS
      0) but among which we include the bitter taste of the squash. The average age of
      PSS 2 patients was significantly (p = .003) older than that of the PSS <2
      patients. CONCLUSION: As the first consequential series in Europe, our study
      shows that exposure to non-edible squash is frequent. Usually benign, poisoning
      could be the consequence of the irritating effect of certain cucurbits, the
      molecules responsible for the taste and toxicity of the fruits. In terms of
      prevention therefore, we recommend disposing of any squash with a bitter taste.

PMID- 29323541
TI  - Development of a Targeted Next-Generation Sequencing Assay to Detect
      Diagnostically Relevant Mutations of JAK2, CALR, and MPL in Myeloproliferative
      Neoplasms.
AB  - BACKGROUND: The classical Philadelphia chromosome-negative myeloproliferative
      neoplasms (MPNs), consisting of polycythemia vera, essential thrombocythemia, and
      primary myelofibrosis, are a heterogeneous group of neoplasms that harbor driver
      mutations in the JAK2, CALR, and MPL genes. The detection of mutations in these
      genes has been incorporated into the recent World Health Organization (WHO)
      diagnostic criteria for MPN. Given a pressing clinical need to screen for
      mutations in these genes in a routine diagnostic setting, a targeted next
      generation sequencing (NGS) assay for the detection of MPN-associated mutations
      located in JAK2 exon 14, JAK2 exon 12, CALR exon 9, and MPL exon 10 was developed
      to provide a single platform alternative to reflexive, stepwise diagnostic
      algorithms. METHODS: Polymerase chain reaction (PCR) primers were designed to
      target mutation hotspots in JAK2 exon 14, JAK2 exon 12, MPL exon 10, and CALR
      exon 9. Multiplexed PCR conditions were optimized by using qualitative PCR
      followed by NGS. Diagnostic genomic DNA from 35 MPN patients, known to harbor
      driver mutations in one of the target genes, was used to validate the assay.
      RESULTS: One hundred percent concordance was observed between the previously
      identified mutations and those detected by NGS, with no false positives, nor any
      known mutations missed (specificity = 100%, CI = 0.96, sensitivity = 100%, CI =
      0.89). Improved resolution of mutation sequences was also revealed by NGS
      analysis. CONCLUSION: Detection of diagnostically relevant driver mutations of
      MPN is enhanced by employing a targeted multiplex NGS approach. This assay
      presents a robust solution to classical MPN mutation screening, providing an
      alternative to time-consuming sequential analyses.

PMID- 29323543
TI  - Effects of molsidomine on retinal ischemia/reperfusion injury in rabbits.
AB  - We investigated the effect of molsidomine (MOL) on ischemia/reperfusion (I/R)
      injury. Rabbits were assigned to four groups: group 1, sham; group 2, I/R; group
      3, MOL treatment for 4 days after I/R; group 4, MOL treatment for 1 day before
      I/R and 3 days after I/R. Retinal I/R was produced by elevating the intraocular
      pressure to 150 mm Hg for 60 min. Seven days after I/R, the eyes were enucleated.
      Retinal changes were examined using histochemistry. The levels of malondialdehyde
      (MDA), glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GSH
      Px) and catalase (CAT) also were measured. We found a significant increase in the
      thickness of the outer nuclear layer of group 3 compared to the other groups. In
      groups 3 and 4, caspase-3 stained cells in the ganglion cell layer were decreased
      compared to group 2. We found a significant increase in caspase-3 stained cells
      in the inner nuclear layer (INL) of group 2 compared to the other groups. We
      found a significant increase in caspase-3 stained cells in group 3 compared to
      group 4 in the INL. The MDA level in group 2 was significantly higher than group
      1 and MOL significantly decreased MDA levels in groups 3 and 4. We found that MOL
      protected the retina from I/R injury by enhancing antioxidative effects and
      inhibiting apoptosis of retinal cells.

PMID- 29323542
TI  - The comparative efficacy of brodalumab in patients with moderate-to-severe
      psoriasis: a systematic literature review and network meta-analysis.
AB  - PURPOSE: To evaluate the relative efficacy of brodalumab compared with approved
      biologic therapies and apremilast for moderate-to-severe psoriasis. METHODS: We
      searched MEDLINE, Embase, and Cochrane for randomized controlled trials reporting
      induction phase responses. The primary analysis examined the proportion of
      patients achieving Psoriasis Area Severity Index (PASI) 50, 75, 90, or 100
      responses using a random-effects Bayesian multinomial likelihood model with
      probit link, with and without adjustment for variation in study-level placebo
      responses. RESULTS: A total of 54 studies were included. Based on PASI 100
      response, the most efficacious therapies were brodalumab 210 mg every two weeks
      (Q2W) and ixekizumab. Brodalumab 210 mg Q2W was significantly more efficacious
      than adalimumab, apremilast, brodalumab 140 mg Q2W, etanercept, infliximab,
      secukinumab, and ustekinumab. Results were consistent for PASI 50, 75, and 90
      outcomes and all sensitivity analyses. CONCLUSIONS: Our findings are consistent
      with pivotal trials which indicate that high levels of complete clearance can be
      achieved with brodalumab. Based on existing evidence, induction-phase efficacy of
      brodalumab is similar to ixekizumab and superior to other approved therapies,
      including anti-TNFs, apremilast, secukinumab, and ustekinumab.

PMID- 29323544
TI  - Transabdominal Ultrasound Detection of Pancreatic Cysts Incidentally Detected at
      CT, MRI, or Endoscopic Ultrasound.
AB  - OBJECTIVE: The objective of our study was to evaluate the detection rate of
      incidental pancreatic cysts on transabdominal ultrasound (TAUS) as well as
      factors influencing detection rates. MATERIALS AND METHODS: Nine hundred thirty
      eight patients with 1064 pancreatic cysts who underwent both TAUS and other
      imaging examinations including CT, MRI, or endoscopic ultrasound (EUS) were
      enrolled. We reviewed formal reports and assessed the effect of cyst size and
      location and the effect of the correlative images for cyst detection on TAUS.
      Statistical analyses were performed using the chi-square test, t test, and Cramer
      value (V). RESULTS: The overall detection rate of TAUS was 88.3% (940/1064).
      Cysts detected on TAUS were more often in younger patients and male patients. The
      detected cysts (median, 13 mm; interquartile range [IQR], 8-18 mm) were
      significantly larger than the undetected cysts (median, 10 mm; IQR, 6-14 mm) (p <
      0.0001). However, waist circumference did not affect the detection rate. The
      detection rate was significantly improved from 49.2% (289/587) to 86.7% (830/957)
      when TAUS was performed after correlative imaging (p < 0.001). Although the
      detection rate for cysts in the entire pancreas was significantly increased with
      correlative images (p < 0.001), the detection rate for cysts in the uncinate
      process showed a much greater increase using correlative images (p < 0.001).
      However, detection of cysts in the tail of the pancreas showed the least
      improvement using correlative images. The detection rate was significantly
      improved with correlative images for cysts 25 mm or smaller. CONCLUSION: Because
      the detection rate of TAUS for pancreatic cysts was significantly improved after
      CT, MRI, or EUS, TAUS could be a useful surveillance imaging tool for pancreatic
      cysts incidentally detected on CT, MRI, or EUS.

PMID- 29323545
TI  - Focal Nodular Hyperplasia After Treatment With Oxaliplatin: A Multiinstitutional
      Series of Cases Diagnosed at MRI.
AB  - OBJECTIVE: Benign hepatic lesions may occur after chemotherapy treatment and may
      mimic metastases at imaging. We describe focal nodular hyperplasia (FNH) lesions
      diagnosed at MRI that occurred de novo after treatment with oxaliplatin.
      MATERIALS AND METHODS: This is a multiinstitutional case series. We report 14
      adult patients with cancer (eight men and six women) with a history of treatment
      with oxaliplatin and development of new hepatic lesions diagnosed as FNH at
      pathologic analysis or MRI or both. Imaging and pathology features of the
      included lesions, the interval since chemotherapy, and the temporal evolution
      were reviewed. RESULTS: The mean interval between the completion of oxaliplatin
      treatment and the identification of new hepatic FNH at imaging was 47.6 months.
      In seven of 14 (50%) patients, the index lesion was diagnosed at pathologic
      analysis (biopsy or resection) as FNH. In the remaining seven cases, the
      diagnosis was based on highly accurate MRI features (e.g., hyper- or isointensity
      of the lesion on hepatobiliary phase images). Lesion growth or occurrence of new
      lesions was present in 75% of patients at imaging follow-up. CONCLUSION: FNH
      lesions can occur de novo after treatment with oxaliplatin. Recognizing the
      typical MRI appearance of these lesions may avoid unnecessary biopsy or surgery
      and reduce patients' anxiety.

PMID- 29323546
TI  - Validation of the 2015 American Thyroid Association Management Guidelines for
      Thyroid Nodules With Benign Cytologic Findings in the Era of the Bethesda System.
AB  - OBJECTIVE: The purpose of this study is to investigate follow-up strategies for
      cytologically benign thyroid nodules according to size and ultrasound (US)
      pattern according to the 2015 American Thyroid Association (ATA) guidelines in
      the era of the Bethesda system. MATERIALS AND METHODS: This retrospective study
      included 1208 patients with 1230 nodules that were cytologically benign at
      initial fine-needle aspiration performed from June 2012 to December 2014. False
      negative rates (FNRs) were calculated by considering nodule size and US pattern
      according to the 2015 ATA guidelines and were compared between nodules with the
      high-suspicion US pattern and nodules with the high- or intermediate-suspicion US
      patterns according to size. RESULTS: Twenty-five of the 1230 nodules (2.0%) were
      malignant. The FNRs were 5.1% (8/158) for nodules with the high-suspicion US
      pattern and 1.6% (17/1072) for nodules with other US patterns. With regard to
      nodule size, the FNRs were 3.2% (9/277) for nodules 3 cm or larger and 5.2%
      (6/115) for nodules 4 cm or larger. The FNRs of nodules with the high-suspicion
      pattern were not significantly higher than those of nodules with the high- or
      intermediate-suspicion patterns among nodules 2 cm or larger (2.5% vs 1.9%; p =
      0.208), 3 cm or larger (3.4% vs 2.9%; p = 0.498), and 4 cm or larger (5.4% vs
      3.8%; p = 0.353). CONCLUSION: Thyroid nodules with initial benign cytologic
      findings had a low malignancy rate in the era of the Bethesda system, regardless
      of US pattern and size. Therefore, any immediate diagnostic intervention may be
      discouraged in cytologically benign nodules.

PMID- 29323547
TI  - Accuracy of CT Attenuation Measurement for Differentiating Treated Osteoblastic
      Metastases From Enostoses.
AB  - OBJECTIVE: The objective of our study was to assess whether the maximum and mean
      CT attenuations are accurate for differentiating between enostoses and treated
      sclerotic metastases. MATERIALS AND METHODS: We retrospectively reviewed CT
      studies of 165 patients (167 lesions) that included 49 patients with 49 benign
      lesions, 69 patients with 71 sclerotic treated lesions, and 47 patients with 47
      untreated lesions, and calculated the mean and maximum CT attenuations of each
      lesion. ROC curves were used to identify thresholds for differentiating enostoses
      from treated sclerotic metastases and from untreated sclerotic metastases.
      RESULTS: The maximum CT attenuation of enostoses (1212.0 HU) was higher from that
      of untreated (754.7 HU) (p = 9.7 * 10-16) and that of treated (891.7 HU) (p = 9.9
      * 10-10) sclerotic metastases. The maximum CT attenuation of treated sclerotic
      metastases (891.7 HU) was higher than that of untreated sclerotic metastases
      (754.7 HU) (p = 0.003). Enostoses had higher mean CT attenuation (1123.0 HU) than
      untreated (602.0 HU) (p < 2.2 * 10-16) and treated (731.7 HU) (p = 9.6 * 10-15)
      sclerotic metastases. A threshold mean CT attenuation of 885 HU had an accuracy
      of 91.7% and 81.7% to differentiate enostoses from untreated and treated
      metastases, respectively, whereas a threshold maximum CT attenuation of 1060.0 HU
      had an accuracy of 81.3% and 72.5% to differentiate enostoses from untreated and
      treated metastases. CONCLUSION: The mean and maximum CT attenuations can
      differentiate between enostoses and sclerotic metastases; however, the accuracy
      of both metrics decreases after treatment.

PMID- 29323548
TI  - 18F-Fluorocholine PET Whole-Body MRI in the Staging of High-Risk Prostate Cancer.
AB  - OBJECTIVE: The purpose of this study was to determine whether integrated 18F
      fluorocholine (FCH) PET whole-body MRI (PET/WBMRI) depicts lymph node and distant
      metastases in patients with high-risk prostate cancer more frequently than does
      conventional staging. SUBJECTS AND METHODS: A prospective study included 58
      patients with untreated high-risk prostate cancer. After conventional staging (CT
      and bone scintigraphy), patients underwent FCH PET/WBMRI (n = 10) or FCH PET/CT
      and WBMRI (n = 48). Metastatic sites and disease stage were recorded for each
      modality (conventional imaging, PET, WBMRI, and PET/WBMRI) and compared with a
      standard of reference (histopathologic examination, imaging, and clinical follow
      up) and early clinical outcomes. RESULTS: In the detection of metastases, PET had
      significantly higher sensitivity (72/77 [93.5%]) than conventional imaging (49/77
      [63.6%]; p < 0.001) and WBMRI (56/77 [72.7%]; p = 0.002). There was a trend
      toward improved detection with PET/WBMRI (77/77 [100%]) compared with PET alone
      (p = 0.059). For correct NM staging, PET and PET/WBMRI performed better than
      conventional imaging (p = 0.002) and WBMRI (p = 0.008). Twelve of 56 patients
      (21.4%) had early biochemical failure after radical treatment (median, 7 months;
      range, 1-20 months). This rate was higher for patients with M1a or M1b disease at
      PET/WBMRI than for others, but this finding did not reach statistical
      significance (4/8 [50%] vs 8/48 [16.7%]; p = 0.055). CONCLUSION: In patients with
      high-risk prostate cancer, FCH PET and FCH PET/WBMRI depict significantly more
      metastatic lesions than do conventional imaging and WBMRI. Stage determined with
      PET/WBMRI may correlate with early outcomes.

PMID- 29323549
TI  - Predicting Parametrial Invasion in Cervical Carcinoma (Stages IB1, IB2, and IIA):
      Diagnostic Accuracy of T2-Weighted Imaging Combined With DWI at 3 T.
AB  - OBJECTIVE: The objective of our study was to retrospectively evaluate the
      efficacy of combined analysis of T2-weighted imaging and DWI in the diagnosis of
      parametrial invasion (PMI) in cervical carcinoma. MATERIALS AND METHODS: The
      clinical records of 192 patients with cervical carcinoma who met the study
      requirements were reviewed for this retrospective study. The signal intensities
      of suspicious PMI tissue were assessed on T2-weighted images, DW images, and
      apparent diffusion coefficient maps independently by two experienced
      radiologists. The radiologist observers predicted the presence of PMI by scoring
      T2-weighted imaging alone and then by scoring T2-weighted imaging and DWI
      combined. The results were compared with histopathologic findings. RESULTS:
      Histopathologic findings revealed PMI in 24 of 192 study subjects. In positively
      predicting the presence of PMI, T2-weighted imaging and DWI combined scored
      significantly better than T2-weighted imaging alone, as proven by high
      sensitivity (T2-weighted imaging alone vs T2-weighted imaging and DWI combined:
      observer 1, 75.0% vs 83.3% [p = 0.477]; observer 2, 66.7% vs 91.7% [p < 0.05]),
      high specificity (T2-weighted imaging alone vs T2-weighted imaging and DWI
      combined: observer 1, 84.5% vs 98.8% [p < 0.001]; observer 2, 85.7% vs 98.8% [p <
      0.001]), and high accuracy (T2-weighted imaging alone vs T2-weighted imaging and
      DWI combined: observer 1, 83.3% vs 96.9% [p < 0.001]; observer 2, 83.3% vs 97.9%
      [p < 0.001]). The area under the ROC curve was also significantly higher for T2
      weighted imaging and DWI combined (observer 1, 0.911; observer 2, 0.952) than for
      T2-weighted imaging alone (observer 1, 0.798; observer 2, 0.762). Although the
      interobserver agreement was good for T2-weighted imaging (kappa = 0.695) and
      excellent for T2-weighted imaging and DWI combined (kappa = 0.753), the
      improvement failed to achieve statistical significance (p = 0.28). CONCLUSION:
      Combined analysis of T2-weighted imaging and DWI enhances the accuracy of
      diagnosing PMI in patients with cervical cancer compared with T2-weighted imaging
      alone.

PMID- 29323550
TI  - Assessing the Effect of Weight-Based Protocol Modifications to Lower Dose for CT
      Guided Hepatic and Renal Tumor Radiofrequency Ablations.
AB  - OBJECTIVE: This study assessed radiation dose after CT-guided percutaneous
      radiofrequency ablations (RFAs) of hepatic and renal tumors and the effect of
      weight-based CT protocol modification for lowering overall dose in these
      procedures. MATERIALS AND METHODS: CT-guided RFA for renal and hepatic ablations
      performed from January 1, 2009, through December 31, 2009, were retrospectively
      reviewed (90 men and 48 women; age, 42-81 years). The radiation dose was recorded
      during each of the following steps: planning, performing, and postprocedure.
      Weight-based protocol modification changes in tube voltage and tube current were
      then applied to renal and hepatic ablations performed subsequently (18 men and 11
      women; age, 48-82 years). Image quality, needle localization, lesion detection,
      ability to detect complications, and overall operator satisfaction were noted for
      each case (score, 1-5). Dose reduction after modification was then calculated.
      RESULTS: Retrospective analysis found a mean (+/- SD) overall CT dose index
      (CTDI) for CT-guided RFA to be 16.5 +/- 2.3 mGy. After protocol modification, the
      mean CTDI decreased to 6.63 +/- 0.67 mGy, a 59.6% reduction overall; for hepatic
      ablations, the reduction was 65.96% (p < 0.0001) and the reduction for renal
      ablations was 38.97% (p = 0.0153). Image quality analysis showed high operator
      satisfaction (3-5), including adequate needle localization (4-5), lesion
      visibility (3-5), and high performer confidence (4-5). Higher dose reduction was
      noted for patients weighing more than 180 lb (82 kg) (p < 0.0001). CONCLUSION:
      Simple weight-based CT protocol modifications can significantly reduce radiation
      dose during CT-guided percutaneous ablations in the liver and kidneys without
      significantly sacrificing image quality.

PMID- 29323552
TI  - Using the American College of Radiology Dose Index Registry to Evaluate Practice
      Patterns and Radiation Dose Estimates of Pediatric Body CT.
AB  - OBJECTIVE: Imaging registries afford opportunities to study large, heterogeneous
      populations. The purpose of this study was to examine the American College of
      Radiology CT Dose Index Registry (DIR) for dose-related demographics and metrics
      of common pediatric body CT examinations. MATERIALS AND METHODS: Single-phase CT
      examinations of the abdomen and pelvis and chest submitted to the DIR over a 5
      year period (July 2011-June 2016) were evaluated (head CT frequency was also
      collected). CT examinations were stratified into five age groups, and examination
      frequency was determined across age and sex. Standard dose indexes (volume CT
      dose index, dose-length product, and size-specific dose estimate) were
      categorized by body part and age. Contributions to the DIR were also categorized
      by region and practice type. RESULTS: Over the study period 411,655 single-phase
      pediatric examinations of the abdomen and pelvis, chest, and head, constituting
      5.7% of the total (adult and pediatric) examinations, were submitted to the DIR.
      Head CT was the most common examination across all age groups. The majority of
      all scan types were performed for patients in the second decade of life. Dose
      increased for all scan types as age increased; the dose for abdominopelvic CT was
      the highest in each age group. Even though the DIR was queried for single-phase
      examinations only, as many as 32.4% of studies contained multiple irradiation
      events. When these additional scans were included, the volume CT dose index for
      each scan type increased. Among the studies in the DIR, 99.8% came from
      institutions within the United States. Community practices and those that
      specialize in pediatrics were nearly equally represented. CONCLUSION: The DIR
      provides valuable information about practice patterns and dose trends for
      pediatric CT and may assist in establishing diagnostic reference levels in the
      pediatric population.

PMID- 29323553
TI  - Revealing the Structural Neural Circuitry of Attention Deficit Hyperactivity
      Disorder With Diffusion MRI: Implications for Future Diagnosis and Treatment.
AB  - OBJECTIVE: Rates of attention deficit hyperactivity disorder (ADHD) diagnosis and
      psychostimulant prescriptions continue to rise, yet there are no clear diagnostic
      tests or biomarkers for the disorder. The purpose of this article is to highlight
      the role of diffusion MRI in bolstering a neurobiologic conceptualization of ADHD
      and how this holds promise for optimizing future diagnosis. CONCLUSION: Diffusion
      MRI is a powerful neuroimaging tool for noninvasive assessment of the structural
      neural circuitry underlying brain function and behavior. Though the modality is
      still in its infancy, diffusion MRI studies are showing neural network disruption
      in ADHD consistent with findings from other imaging modalities. Given the
      mounting evidence of brain-behavior correlates in ADHD, it is likely that imaging
      based biomarkers will one day be incorporated into clinical diagnosis and
      treatment evaluation. Until then, diffusion MRI findings serve to validate ADHD
      as a brain-based disorder with immediate public health implications for
      individuals with ADHD.

PMID- 29323551
TI  - Gamma Imaging-Guided Minimally Invasive Breast Biopsy: Initial Clinical
      Experience.
AB  - OBJECTIVE: The purpose of this study was to evaluate our initial experience with
      gamma imaging-guided vacuum-assisted breast biopsy in women with abnormal
      findings. MATERIALS AND METHODS: A retrospective review of patients undergoing
      breast-specific gamma imaging (BSGI), also known as molecular breast imaging
      (MBI), between April 2011 and October 2015 found 117 nonpalpable mammographically
      and sonographically occult lesions for which gamma imaging-guided biopsies were
      recommended. Biopsy was performed with a 9-gauge vacuum-assisted device with
      subsequent placement of a titanium biopsy site marker. Medical records and
      pathologic findings were evaluated. RESULTS: Of the 117 biopsies recommended, 104
      were successful and 13 were canceled. Of the 104 performed biopsies, 32 (30.8%)
      had abnormal pathologic findings. Of those 32 biopsies, nine (28.1%) found
      invasive cancers, six (18.8%) found ductal carcinoma in situ (DCIS), and 17
      (53.1%) found high-risk lesions. Of the 17 high-risk lesions, there were three
      (17.6%) lobular carcinomas in situ, five (29.4%) atypical ductal hyperplasias,
      two (11.8%) atypical lobular hyperplasias, one (5.9%) flat epithelial atypia, and
      six (35.3%) papillomas. Two cases of atypical ductal hyperplasia were upgraded to
      DCIS at surgery. The overall cancer detection rate for gamma imaging-guided
      biopsy was 16.3%. In this study, gamma imaging-guided biopsy had a positive
      predictive value of total successful biopsies of 16.3% for cancer and 30.8% for
      cancer and high-risk lesions. CONCLUSION: Gamma imaging-guided biopsy is a viable
      approach to sampling BSGI-MBI-detected lesions without sonographic or
      mammographic correlate. Our results compare favorably to those reported for MRI
      guided biopsy.

PMID- 29323554
TI  - Insights Into Breast Cancer Screening: A Computer Simulation of Two Contemporary
      Screening Strategies.
AB  - OBJECTIVE: The debate over the value of screening mammography is rekindled with
      each new published study or guideline. Central to the discussion are the
      uncertainties about screening benefits and harms and the criteria used to assess
      them. Today, the magnitude of benefits for a population is less certain, and the
      evolving concept of harm has come to encompass false-positives (FPs), unnecessary
      biopsies, overdiagnosis, and overtreatment. This study uses a Monte Carlo
      computer simulation to study the balance of benefits and harms of mammographic
      breast cancer screening for average-risk women. MATERIALS AND METHODS: This
      investigation compares the American Cancer Society's 2015 mixed annual-biennial
      guideline with the U.S. Preventive Services Task Force's 2016 fixed biennial
      guideline. Screening strategies are compared using cost-effectiveness
      acceptability curves, an economic analysis describing uncertainty in evaluating
      costs and health outcomes. Strategy preference is examined under changing
      assumptions of willingness to pay for a quality-adjusted life-year. Additionally,
      comparative effectiveness analysis is performed using FP screens and unnecessary
      biopsies per life-year gained. Alternative scenarios are compared assuming a
      reduced mortality benefit of screening. RESULTS: In general, results using both
      cost-effectiveness and clinical measures indicate that American Cancer Society's
      2015 mixed annual-biennial guideline is preferred. Assuming decreases in the
      mortality benefit of mammography, no screening may be reasonable. CONCLUSION: The
      use of a mixed annual-biennial strategy for population screening takes advantage
      of the nonuniformity of occurrence of mammography benefits and harms over the
      duration of screening. This approach represents a step toward improving
      guidelines by exploiting age dependencies at which benefits and harms accrue.

PMID- 29323555
TI  - Practical Suggestions on How to Move From Peer Review to Peer Learning.
AB  - OBJECTIVE: The purpose of this article is to outline practical steps that a
      department can take to transition to a peer learning model. CONCLUSION: The 2015
      Institute of Medicine report on improving diagnosis emphasized that organizations
      and industries that embrace error as an opportunity to learn tend to outperform
      those that do not. To meet this charge, radiology must transition from a peer
      review to a peer learning approach.

PMID- 29323557
TI  - Neuropsychological Assessment of 412 HIV-Infected Individuals in Sao Paulo,
      Brazil.
AB  - HIV-associated neurocognitive disorders (HAND) remain frequent even among
      individuals receiving combined antiretroviral therapy (cART). In addition, HAND
      may adversely affect the quality of life and adherence to cART. There is scarce
      epidemiological information about HAND in Latin America. This cross-sectional
      study recruited HIV-infected patients from a tertiary teaching institution in Sao
      Paulo, Brazil, between May 2013 and February 2015. The patients were adults with
      at least 4 years of education and patients with current neurological or
      psychiatric diseases were excluded. HAND remain frequent even among individuals
      receiving cART, use of psychoactive substance, or inability to understand the
      content for neuropsychological evaluation. We used standardized tools to evaluate
      depression, use of psychoactive substances, and daily life activities, and we
      performed a comprehensive neuropsychological examination. HAND was classified
      using the Frascati criteria. Prevalence of HAND was estimated, and an associated
      variable of symptomatic HAND was identified by logistic regression. Four-hundred
      twelve HIV-infected patients were included [male: 281 (68%), mean age of 45.3
      years]. Most of them [n = 340 (83.7%)] had an undetectable viral load. The
      prevalence of HAND was 73.6% (n = 303): 210 (50.9%) had asymptomatic
      neurocognitive involvement (ANI), 67 (16.2%) had mild neurocognitive disorder
      (MND), and 26 (6.3%) had HIV-associated dementia (HAD). The univariate logistic
      regression analysis showed that female gender, age older than 50 years, <11 years
      of schooling, CD4 count below 200 cells/mm3, presence of previous illnesses
      (e.g., diabetes, hypertension), opportunistic disease history, and a Beck
      Depression Inventory (BDI) score between 13 and 19 points were factors associated
      with symptomatic HAND (MND and HAD). However, a BDI score between 13 and 19
      points was the single independent variable associated with symptomatic HAND. HAND
      was highly prevalent in Sao Paulo, Brazil, and ANI was the more frequent category
      of HAND. However, 22.5% of participants had symptomatic HAND. This finding
      constitutes a challenge in clinical practice. A BDI score between 13 and 19
      points was the single independent variable associated with symptomatic HAND.

PMID- 29323556
TI  - Modality of Primary HIV Disclosure and Association with Mental Health, Stigma,
      and Antiretroviral Therapy Adherence in Tanzanian Youth Living with HIV.
AB  - Disclosing HIV status to children before adolescence is a major challenge facing
      families and healthcare providers. This study used a mixed methods approach to
      explore the youth perspective of how youth living with HIV (YLHIV) found out
      their status and to quantify the association of disclosure modality with mental
      health, stigma, adherence, and HIV outcomes in adolescence. Youth 11-24 years of
      age attending adolescent HIV clinic in Moshi, Tanzania were included. Adolescents
      answered questions, including when and how they found out they had HIV, mental
      health surveys (nine-item Patient Health Questionnaire, Strengths and
      Difficulties Questionnaire, and modified University of California Los Angeles
      trauma screen), modified Berger's stigma scale, and self-reported adherence. HIV
      1 RNA and latest CD4 were obtained. In-depth interviews were conducted using a
      convenience sample. The majority of youth reported that they found out their HIV
      status on their own (80%). Youth attending the government site were less likely
      to be purposefully told their HIV status compared with those attending the
      referral site (p < 0.01). Depressive and emotional/behavioral symptoms, internal
      stigma, and incomplete adherence were significantly more likely among those who
      figured out their HIV status on their own as compared with those who were
      purposefully told. Youth discussed how they figured out their HIV status on their
      own during in-depth interviews. These findings demonstrated that youth who
      figured out their HIV status on their own had increased mental health symptoms
      and worse adherence to antiretroviral therapy (ART). It is imperative to
      implement disclosure protocols in early childhood to reduce mental health
      difficulties, internal stigma, and promote ART adherence in YLHIV.

PMID- 29323559
TI  - Reply to letter to editor regarding: Risk of bacterial vaginosis, Trichomonas
      vaginalis and Candida albicans infection among new users of combined hormonal
      contraception compared to levonorgestrel-releasing intrauterine system.

PMID- 29323558
TI  - Optimizing Delivery of HIV Preexposure Prophylaxis for Women in the United
      States.
AB  - Preexposure prophylaxis (PrEP) is a highly effective HIV prevention method;
      however, it is underutilized among women who are at risk for acquisition of HIV.
      Women comprise one in five HIV diagnoses in the United States, and significant
      racial disparities in new HIV diagnoses persist. The rate of new HIV diagnoses
      among black and African American women in 2015 was 16 times greater than that of
      white women. These disparities highlight the importance of HIV prevention
      strategies for women, including the use of PrEP. PrEP is the first highly
      effective HIV prevention method available to women that is entirely within their
      control. However, because so few women who may benefit from PrEP are aware of it,
      few women's healthcare providers offer PrEP to their patients, PrEP has not yet
      achieved its potential to reduce HIV infections in women. This article describes
      individual and systemic barriers for women related to the uptake of PrEP
      services; explains how providers can identify women at risk for HIV; reviews how
      to provide PrEP to women; and outlines client-centered models for HIV prevention
      services. Better access to culturally acceptable and affordable medical and
      social services may offer support to women for consistent and ongoing use of
      PrEP. This discussion may be used to inform HIV prevention activities for women
      and guide interventions to decrease racial/ethnic disparities in rates of HIV
      infection among US women.

PMID- 29323560
TI  - The prospects for combination therapy with capecitabine in the rapidly evolving
      treatment landscape of renal cell carcinoma.
AB  - INTRODUCTION: Although significant advances have been made in the treatment of
      advanced renal cell carcinoma (RCC), patients still develop resistance to
      standard therapies and require the administration of subsequent lines of
      treatment. New therapeutic approaches are thus imperative to improve the
      prognosis for patients with RCC. Areas covered: Based on the current literature,
      we summarize the treatment of metastatic RCC, including the use of cytotoxic
      chemotherapy, in this review article. We also review the existing scientific
      literature regarding the role of capecitabine in the treatment of RCC. Expert
      opinion: Currently, targeted therapies including vascular endothelial growth
      factor (VEGF) and mammalian target of rapamycin (mTOR) inhibitors are widely used
      in the treatment of metastatic RCC. More recently, the role of immune checkpoint
      inhibitors has been established in the treatment of advanced RCC. Traditionally,
      the use of cytotoxic chemotherapy in the treatment of RCC is limited. However,
      cytotoxic chemotherapy may have benefit in different types of RCC, such as
      variant histology. Furthermore, new combinations of chemotherapy with immune
      checkpoint inhibitors may provide new treatment options for our patients.

PMID- 29323561
TI  - Developing a nursing approach to managing dyspnoea in lung cancer.
AB  - Dyspnoea, or breathlessness, is a common problem in lung cancer and is frequently
      difficult to alleviate. Most studies exploring strategies for dyspnoea
      intervention have focused on pharmacological intervention. The approach described
      in this article has been developed through an evaluative study of a nursing
      clinic for lung cancer patients with breathlessness. It used an integrative model
      of dyspnoea and techniques derived from chronic pulmonary disease rehabilitation.
      Case examples suggest that this may offer a positive intervention approach in
      breathlessness management by nurses.

PMID- 29323562
TI  - The need for an International Journal of Palliative Nursing.
AB  - Responses to the launch of a new journal may vary from pleasure and satisfaction,
      to a total lack of interest or even frustration. 'Oh no, not another journal!',
      someone will exclaim and, in certain circumstances, this may be a reasonable
      reaction. However, in the case of the International Journal of Palliative
      Nursing, it certainly is not. For a variety of reasons, I believe its launch is
      both timely and appropriate. So, why do we need this journal?

PMID- 29323563
TI  - The challenges of conducting clinical trials in palliative care.
AB  - Research is a prerequisite for every specialty; palliative care is no exception.
      Clinical observation and anecdotal evidence are insufficient, and well designed
      scientific clinical research trials are required to promote advances within the
      specialty. Certain challenges exist for the researcher. This article will discuss
      these demands with reference to informed consent, factors which influence accrual
      (recruitment) and attrition rates (the loss of participants during the course of
      a study (Polit and Hungler, 1991), prevailing attitudes and clinical research
      design.

PMID- 29323564
TI  - Development of palliative care in Norway: an overview.
AB  - This article looks at the development of palliative care and the hospice movement
      in Norway during the last 15 years. The development of specialist hospital and
      community services and the hospice movement in Norway are discussed. These are
      considered against the background of similar developments elsewhere in Europe and
      the USA and in the context of research into care of the dying. Key events, such
      as the formation of the Norwegian Committee on Terminal Care (NCTC) and
      government directives and their influence are described.

PMID- 29323565
TI  - Conducting research with the dying: ethical considerations and experience.
AB  - This article explores the ethical considerations that arose during a qualitative
      evaluation study of an Australian domiciliary palliative care agency. The
      research sought to answer the question: 'What is the relationship between
      palliative care philosophy and that received by dying clients and their primary
      carer?'. Interviews were conducted with clients, carers and agency staff, which
      exposed particular issues relating to the protection of vulnerable groups such as
      the dying. The fact that key aspects of research ethics can only be understood
      when the context of people's lives and experiences are taken into account is
      explained. Questions raised during the implementation of the study illustrate the
      complexity of research ethics and form the basis of the discussion.

PMID- 29323566
TI  - Comments welcoming the launch of the International Journal of Palliative Nursing.
AB  - Madam, It was with great delight that I learnt of your new journal. I am sure
      that other nurses will be just as enthusiastic. Palliative nursing needs a
      scholarly vehicle to encourage research-based practice and to im prove care.
      Researchers also need a journal in which to publish the ever increasing number of
      studies in this area. May you be overwhelmed with manuscripts!

PMID- 29323567
TI  - The development of an audit tool for Macmillan nurses.
AB  - Recent NHS reforms in the UK have stressed the importance of developing services
      that are in line with the preferences of patients. The desire to gauge the
      satisfaction of patients and carers with Macmillan nursing services led to the
      development of an audit tool for Macmillan nurses to use in hospitals or the
      community. This article describes the components of the audit tool and discusses
      its development. It concludes with a brief discussion of the issues arising from
      the pilot phase of the audit tool.

PMID- 29323568
TI  - A reflection on 6 years of hospice work.
AB  - Six years of working in palliative care have left me with a need to explain my
      experiences.

PMID- 29323569
TI  - Nurses' estimations of patients' prognoses in the last days of life.
AB  - This study was based on two medical wards in a teaching hospital. It examined the
      accuracy with which nurses estimated patients' prognoses in the last days and
      hours of life and the cues used to make such assessments. An exploratory and
      descriptive approach was adopted. The study was divided into two parts: a cross
      sectional interview study and a prospective patient follow-up study. The cues
      used by the nurses were identified and categorised and estimates of life
      expectancy were assessed for accuracy. Results showed that multiple cues were
      used and that although nurses were able to identify patients who were dying
      imminently, their accuracy regarding precise prognosis varied considerably. They
      also revealed that the most accurate assessments were made by nurses carrying out
      basic patient care, rather than the most experienced staff.

PMID- 29323570
TI  - Aromatherapy and massage in palliative care.
AB  - Aromatherapy and massage have gained wide popularity among nurses in clinical
      practice in recent years. Many nurses in palliative care settings are using these
      therapies with the assumption that they improve patients' quality of life, but no
      research has yet investigated their effectiveness. A study was set up to assess
      the effects of massage and aromatherapy massage on cancer patients receiving
      palliative care. Patients received three full body massages over a 3-week period,
      with or without the essential oil Roman Chamomile. The measurements used were the
      Rotterdam Symptom Checklist (RSCL) and State-Trait Anxiety Inventory. Post-test
      scores for all patients improved. These were statistically significant in the
      aromatherapy group on the RSCL physical symptom subscale, quality of life
      subscale and state anxiety scale. Responses to the post-therapy questionnaire
      indicate that patients consider the massage or aromatherapy to be beneficial in
      reducing anxiety, tension, pain and depression.

PMID- 29323571
TI  - Sociological factors and psychosocial implications of lymphoedema.
AB  - Lymphoedema can affect many patients with cancer, either as a result of treatment
      or in the advanced stages of disease. This article outlines some of the
      sociological and psychosocial factors that were found to be significant in the
      management of arm swelling. Older and working women were found to have
      significantly larger swollen arms. Arm size also increased when swelling had been
      present for a greater period. The psychosocial implications of lymphoedema
      appeared to be complex and unique to the individual.

PMID- 29323572
TI  - Palliative care in developing countries: luxury or necessity?
AB  - Palliative care is not a luxury in developing countries. This article challenges
      the assumption that money spent on the care of people who are terminally ill
      cannot be justified in the face of many competing claims. The absence of
      screening and diagnostic services, combined with a cultural reluctance to seek
      help, frequently results in patients presenting at a late stage in the natural
      history of their disease. Pain and symptom relief remain the only options. In
      developing countries, the health care systems and social networks are often
      inadequate to support terminally ill members of society and it is argued that
      palliative care home teams would provide the ideal model of care. Palliative
      care's eligibility for inclusion in the health care budget of Kenya is
      demonstrated in this article and the difficulties it is facing in other
      developing countries are described. A case history seeks to show the necessity of
      palliative care in these areas of the world.

PMID- 29323574
TI  - Authors' reply to letter to the editor: Lidocaine gel vs lidocaine spray in
      reducing pain during insertion of the intrauterine contraceptive device.

PMID- 29323575
TI  - Phase II investigational oral drugs for the treatment of radio/chemotherapy
      induced oral mucositis.
AB  - INTRODUCTION: Oral mucositis is a significant unmet clinical need for many cancer
      patients. The biological complexity of mucositis' pathogenesis provides a number
      of mechanistic targets suitable as pharmacologic targets. The diversity of
      targets has stimulated drug development in search of an effective intervention.
      In this paper, we review a range of agents that are currently being evaluated.
      Areas covered: Drugs for management of oral mucositis vary in formulation, route
      of administration and biological target. Most propose to interrupt the initiation
      of injury by suppressing activation of the innate immune response or countering
      oxidative stress, or minimizing downstream inflammatory responses.
      Overwhelmingly, the population most studied is patients being treated with
      concomitant chemoradiation for cancers of the head and neck as this is the cohort
      that most consistently suffers severe mucositis for long periods of time. The
      Phase 2 pipeline is robust. Preliminary data reported for a number of agents is
      optimistic. Genomics may be important in interpreting and comparing responses to
      agents across widely demographically diverse populations. Expert opinion: Oral
      mucositis remains a significant toxicity for patients undergoing cancer
      treatment. Incremental reports of successes have been noted for a number of
      targeted agents.

PMID- 29323576
TI  - Preserving the reproductive potential of transgender and intersex people.
AB  - BACKGROUND: The bodies of some transgender and intersex people have been
      mutilated and their minds subjected to immense distress. Their gender has often
      been determined by others. Loss of fertility used to be considered an inevitable
      consequence of treatment. OBJECTIVE: To review the issue of preserving the
      reproductive potential of transgender and intersex people. METHODS: A narrative
      review based on a wide-ranging search of the literature in multiple disciplines.
      RESULTS: Major technological advances have facilitated reproduction for
      transgender and intersex people in the last few years. A majority of trans-adults
      believe that fertility preservation should be offered to them. Deferment of
      surgery for intersex people is often best practice; gonadectomy in infancy closes
      off fertility options and determines a gender they may later regret. CONCLUSIONS:
      Transgender and intersex people should be able to consent to or decline
      treatment, especially radical surgery, themselves. Preservation of reproductive
      potential and sexual function must be given a high priority. Treatment by
      multidisciplinary teams can provide a strong emphasis on mental health and well
      being. Detailed information about options, an absence of any coercion and enough
      time are all needed in order to make complex, life-changing decisions.

PMID- 29323578
TI  - Effects of black cohosh and estrogen on core body and tail-skin temperatures in
      ovariectomized rats by telemetric monitoring with dual thermistor probes.
AB  - OBJECTIVES: To investigate the effects of black cohosh and estrogen on the
      temperature in ovariectomized rats, the core body temperature (CBT) and tail-skin
      temperature (TST) were simultaneously monitored and the relationship between
      these two temperatures was explored. METHODS: Twenty-four female Sprague-Dawley
      rats aged 8 weeks were randomly divided into four groups: sham-operated (SHAM),
      ovariectomized (OVX), OVX treated with estradiol valerate (OVX + E), and OVX
      treated with isopropanolic black cohosh extract (OVX + ICR). Rats were sham
      operated or ovariectomized and were implanted with telemetry transmitters with
      dual thermistor probes. Two weeks after surgery, the animals were treated with
      drugs for 4 weeks. During the last week of the treatments, the dynamic
      temperature profiles of the CBT and TST were collected. RESULTS: The average CBT
      and TST, TST fluctuation frequency, and the average amplitude fluctuation were
      significantly higher in OVX than in SHAM rats. In addition, dramatic fluctuations
      of TST in OVX rats occurred at the time points of the day when the CBTs were
      lower in OVX rats than in SHAM rats. Treatment of OVX rats with estradiol
      valerate or isopropanolic black cohosh extract markedly decreased the average CBT
      and TST, TST fluctuation frequency, and the average amplitude fluctuation.
      Moreover, CBT was found to be significantly higher, while TST was lower in OVX +
      E than in OVX + ICR rats. CONCLUSIONS: Both black cohosh and estradiol treatments
      ameliorated the abnormal thermoregulation in OVX rats. In particular, black
      cohosh reduced CBT better than estradiol and estradiol reduced TST better than
      black cohosh.

PMID- 29323577
TI  - Ongoing or previous mental disorders predispose to adverse mood reporting during
      combined oral contraceptive use.
AB  - PURPOSE: Previous studies have emphasised that women with pre-existing mood
      disorders are more inclined to discontinue hormonal contraceptive use. However,
      few studies have examined the effects of combined oral contraceptives (COC) on
      mood in women with previous or ongoing mental disorders. MATERIALS AND METHODS:
      This is a supplementary analysis of an investigator-initiated, double-blinded,
      randomised clinical trial during which 202 women were treated with either a COC
      (1.5 mg estradiol and 2.5 mg nomegestrolacetate) or placebo during three
      treatment cycles. The Mini International Neuropsychiatric Interview was used to
      collect information on previous or ongoing mental disorders. The primary outcome
      measure was the total change score in five mood symptoms on the Daily Record of
      Severity of Problems (DRSP) scale in the intermenstrual phase of the treatment
      cycle. RESULTS: Women with ongoing or previous mood, anxiety or eating disorders
      allocated to COC had higher total DRSP Delta-scores during the intermenstrual
      phase of the treatment cycle in comparison with corresponding women randomised to
      placebo, mean difference 1.3 (95% CI 0.3-2.3). In contrast, among women without
      mental health problems, no difference in total DRSP Delta-scores between COC- and
      placebo users was noted. Women with a risk use of alcohol who were randomised to
      the COC had higher total DRSP Delta-scores than women randomised to placebo, mean
      difference 2.1 (CI 95% 1.0-3.2). CONCLUSIONS: Women with ongoing or previous
      mental disorders or risk use of alcohol have greater risk of COC-induced mood
      symptoms. This may be worth noting during family planning and contraceptive
      counselling.

PMID- 29323579
TI  - A comparative study of patients' and nurses' perceptions of pain relief.
AB  - Visual analogue scales were used to assess pain and pain relief in a sample of 20
      cancer patients. Simultaneously, the nurse caring for the patient was asked to
      assess the status of the patient's pain. The scores were compared to distinguish
      any differences between the two groups. The two groups were also asked to mark on
      a schematic body diagram the location of the patient's pain. Six nurses were
      interviewed to elicit information about their approach to pain relief. The
      results suggest that there is a discrepancy between the patients' and the nurses'
      pain ratings. The nurses overestimated the patients' pain in the majority of
      cases. These results were not anticipated as recent studies have shown that
      nurses generally underestimate patients' pain. This highlights the nurses' lack
      of detailed knowledge concerning the patients' pain. In the interviews the nurses
      demonstrated an awareness of the basis of pain assessment; however, the results
      of the study suggest that this knowledge is not applied in practice.

PMID- 29323580
TI  - Quality through partnership.
AB  - Examination of the relationship between practice and education inspired the
      development of a model demonstrating that their partnership is essential in order
      to assure quality palliative care. The political, professional and personal
      influences that form the model's boundaries highlight the fact that palliative
      care is not only in a position to adopt change, but also to be proactive in
      influencing and effecting change. While the model was developed in the context of
      palliative care, it is equally applicable to other specialties.

PMID- 29323581
TI  - Palliative nursing and managed care.
AB  - The origins of modern palliative nursing lay in social changes during the 1950s
      and 1960s. In Europe and North America, pioneers in the social sciences cracked
      open the cultural silence about death and dying which was pervasive at that time.
      Pioneers in clinical practice fostered the establishment of the hospice as a
      service to humanise the experience of terminal illness and treat the distressing
      symptoms of painful dying. Both efforts were part of a social movement to improve
      the health and wellbeing of vulnerable people isolated from effective care by
      cultural norms and taboos about death.

PMID- 29323582
TI  - Implications of pet-facilitated therapy in palliative nursing.
AB  - Pet therapy is reviewed in terms of its history, physical and psychological
      benefits and potential problems. There are many reasons why pet therapy is
      ideally suited to palliative care and these are discussed. The introduction of an
      appropriate pet to a hospice or palliative care unit/service is described and
      possible pitfalls are identified.

PMID- 29323583
TI  - Developing a home chemotherapy service.
AB  - Achemotherapy at home service was established to meet the needs of the Walsall
      community by providing greater flexibility of choice for patients requiring
      outpatient chemotherapy. The aim was to extend existing services to meet the
      individual needs of patients with advanced disease who would benefit from
      palliative chemotherapy treatment but, who may, for physical or social reasons,
      find it difficult to attend hospital. Multidisciplinary collaboration, a home
      nursing assessment and a joint care plan with ongoing patient education and
      support, formed key elements of the home chemotherapy programme. Specific
      considerations regarding the safe handling of cytotoxic drugs and waste products
      in the community had to be addressed. The treatment of a sample of five patients
      in their own homes has been achieved, demonstrating the effectiveness and
      feasibility of such a service. A patient satisfaction survey and professional
      audit system are used, in order to measure its progress and assess future
      development needs.

PMID- 29323584
TI  - Readers react to the launch of the IJPN and highlight a promising future for
      nursing research in palliative care.
AB  - Madam, Congratulations on a most timely, well-presented and highquality
      publication. We in New Zealand are particularly impressed with the international
      scope of your journal, being isolated in distance from Europe. We are developing
      closer ties with Australia and the Pacific Rim, but we have a lot to offer and
      learn, and therefore an international forum to share expertise is timely.

PMID- 29323585
TI  - Role of complementary therapies in HIV/AIDS.
AB  - Complementary is a commonly used term to describe therapies that were viewed as
      alternatives to conventional medicine. This change in thinking is important when
      considering their use for people with human immunodeficiency virus (HIV) or
      acquired immunodeficiency syndrome (AIDS). As orthodox medicine can offer support
      but not a cure for this condition, people with HIV/AIDS are seeking help from a
      variety of complementary therapies to enhance wellbeing and quality of life. This
      approach has also been adopted by many people living with other life-threatening
      illnesses such as cancer, where conventional medicine currently offers few
      guarantees of cure or remission. This article will focus on complementary
      therapies and the reasons for their use by people with HIV and AIDS, given the
      limits of current scientific research in this field. The qualities required by
      professionals offering complementary therapies and the close link of these
      therapies to the psychological and spiritual aspects of care for people with
      HIV/AIDS will be addressed.

PMID- 29323586
TI  - Research priorities in palliative care.
AB  - Using the Delphi technique, social workers, occupational therapists,
      physiotherapists, chaplains, doctors and two groups of nurses were surveyed to
      determine priorities for clinical research in palliative care. The total number
      of panellists was 1304 and, of these, 821 completed all three rounds of the
      survey. Problem statements were generated from data supplied by panellists in
      each of the six groups. Subsequent rounds were conducted to enable panellists to
      (a) rank questions to determine their top 10 priority items and (b) indicate
      those items for which their own professional group should take research
      leadership. None of the items identified as research priorities appeared in the
      top 10 lists of all six groups. However, a number of items were selected by
      several of the groups. These included multi-professional teamwork and symptom
      management. A number of items, including the needs of informal carers and aspects
      of spiritual care, were selected by only one of the groups.

PMID- 29323587
TI  - Specialist nursing practice.
AB  - April 1st was an important date for nurses in the UK as, after several years of
      preparation and planning, the long-awaited standards for postregistration
      education and practice (PREP) finally became a reality. Formulated by the United
      Kingdom Central Council for Nursing, Midwifery and Health Visiting (UKCC), these
      standards define what nurses must do in order to maintain their status on the
      UKCC register. They also set out the framework of postregistration education and
      practice required for specialist, community and advanced nursing practice (UKCC,
      1994).

PMID- 29323588
TI  - An evaluation of the use of massage and essential oils on the wellbeing of cancer
      patients.
AB  - Massage and aromatherapy are being used increasingly by nurses to enhance the
      wellbeing of patients in palliative care settings, yet little evaluation of these
      therapies has been undertaken. This article reports a quasi experimental study
      comparing the effects of an 8-week course of massage, with or without the
      addition of a blend of essential oils, on patients undergoing cancer treatment.
      Findings from the study suggest that massage has a significant effect on anxiety
      and this was found to be greater where essential oils were used, although the
      small sample prevented this from being established conclusively. Massage was
      reported to be universally beneficial by patients, it assisted relaxation and
      reduced physical and emotional symptoms. The authors call for more research to be
      conducted in this area with larger cohorts of patients. Copies of the full
      research report for this study may be obtained from the Macmillan Practice
      Development Unit, Centre for Cancer and Palliative Care Studies, Institute of
      Cancer Research/Royal Marsden NHS Trust, Fulham Road, London SW3 6JJ. Price
      L6.00.

PMID- 29323589
TI  - Palliative care services for ethnic groups in Leicester.
AB  - The objectives of this study were to examine current palliative care service
      provision and its use by the black and minority ethnic (BME) groups in
      Leicester.* The study comprised two stages, an initial pilot study using
      semistructured tape recorded interviews, followed by a structured interview
      schedule. It was set in the voluntary sector, a local hospice and one trust
      hospital in Leicester. The subjects were 33 palliative care patients and carers
      from BME groups. The findings identify some deficiencies in access to and
      provision of palliative care services to BME communities in the city of
      Leicester. There appears to be a low level of satisfaction among the sample.
      There are also differences within the group, with 50% indicating that things are
      unsatisfactory. The main area of need identified was information about illness
      and available services. The study concluded that providers of palliative care
      need to examine their policy and practices with regards to whether they are
      acceptable, accessible and culturally sensitive to the needs of BME groups. A low
      uptake of services is more likely to suggest inappropriate provision rather than
      lack of need. An extended version of this article appears in Richardson and
      Wilson Barnett (1995). *The term black and minority ethnic (BME) group has been
      used to refer to people from racial or other minorities who may be disadvantaged
      because of their racial bakground. There is no single accepted term, nor one that
      can be seen as politically correct or incorrect. It should, however, be
      recognised that there may be some people who do not identify themselves as black
      or a minority but who share a common experience of racism (Anthias, 1992; Cole,
      1993).

PMID- 29323590
TI  - Feasibility of education programmes in palliative care for nurses in Europe.
AB  - In September 1994, a group of nurses met for 3 days in London under the auspices
      of the European Oncology Nursing Society (EONS), supported by funds from the
      European Community Europe Against Cancer Programme (ECEACP) and the UK charity,
      the Cancer Relief Macmillan Fund (CRMF).

PMID- 29323591
TI  - Inside story: chaplain at work.
AB  - This is a personal account of how I seek to accompany a person who is dying.

PMID- 29323592
TI  - Truth-telling and collusion: the ethical dilemmas of palliative nursing.
AB  - Within the context of caring for a patient receiving palliative care, it is
      probable that a nurse will encounter a number of ethical dilemmas. Controversy
      will often be the partner of ethics in any discussion. This article looks at
      differing stances taken by opposing camps and offers an unbiased look at both
      sides of the debate, focusing on truth-telling and collusion. Case histories are
      analysed within a framework of ethical theory.

PMID- 29323593
TI  - Short reports.
AB  - American Oncology Nursing Society congress The third international conference on
      children and death Annual scientific meeting of the European Association of
      Cancer Education Launch of nurse-led initiatives in lung cancer care.

PMID- 29323594
TI  - District nurses' views on the role of rehabilitation in palliative care.
AB  - Recently, there has been a surge of interest in the notion that rehabilitation
      should become an integral part of palliative care. The World Health Organization
      (WHO; 1987) asserts that integrating a rehabilitative approach will assist in
      achieving the aims of palliative care by enhancing the patient's quality of life.
      However, WHO suggests that health-care workers have not yet appreciated the
      opportunities presented by this approach in order to be able to succeed in
      achieving the aims of palliative care. District nurses (DNs) are in a key
      position to integrate the philosophy of rehabilitation and their approach to
      palliative care. A small study was undertaken to investigate the beliefs of DNs
      in relation to rehabilitation in palliative care, specifically with regards to
      patients with cancer. The findings demonstrated that DNs generally support the
      view that rehabilitation has a role to play in palliative care. However, barriers
      which, according to the literature, prevent a rehabilitative approach being used
      were identified as problematic for this sample group. The findings have helped to
      identify areas that should be addressed; these have implications for clinical
      practice, management of resouces and education.

PMID- 29323595
TI  - Palliative care nursing in France: a personal perspective.
AB  - This article gives an account of a visit to palliative care services in France
      and identifies the benefits to be gained from the cross-fertilisation of ideas
      from a different European culture. Most of the challenging issues around terminal
      illness and death are experienced by the French, but palliative care provision
      has not been developed and established within the health-care system to the
      extent that it has in Britain. The role of the clinical nurse specialist (CNS) in
      palliative care in France closely matches the role of the palliative care CNS in
      Britain. Nurse-led community teams in France have the potential to develop
      specialist care practice in a way that will maximise the nursing role, enhance
      patient care and disseminate the principles of good practice.

PMID- 29323596
TI  - Stress and staff support in hospice: a review of the literature.
AB  - An extensive review of the literature was carried out which highlighted the
      causes and effects of stress, both generally and in palliative care, along with
      the coping strategies for stress. The literature emphasised the intense nature of
      palliative care and the importance of having effective support mechanisms in
      place for staff.

PMID- 29323597
TI  - Development of hospice care at Methodist Hospital.
AB  - Patients who are terminally ill in hospital are one type of the patient
      population affected by health-care reform. A hospital-hospice programme may be an
      appropriate alternative for their care. This article describes the process of
      creating a hospital-hospice programme. In order to identify the potential patient
      population, a review of the charts of all patients who died at Methodist Hospital
      over a 3-month period was carried out by the hospice medical director. The
      purpose of this review was to identify 'hospice-appropriate' patients and to
      determine the number of days of the patients' hospital stay that were appropriate
      for hospice care. The costs of the 'appropriate' hospice patients were reviewed
      to evaluate whether a reduction in charges would be accomplished by the
      implementation of this programme. The reduction in charges included treatment and
      tests that would not have been undertaken had the 'hospice-appropriate' patient
      been admitted to the hospital-hospice programme. A reduction in charges totalling
      several hundred thousand dollars occurred during the first year of the hospital
      hospice programme's existence.

PMID- 29323598
TI  - The partner's experience of breast cancer: a phenomenological approach.
AB  - The aim of this study is to describe the immediate 'lived experience' of partners
      of breast cancer patients. Previous attempts to explore the reactions and
      feelings of partners have been restricted mainly to quantitative research
      methods. While these methods are valuable in collecting information on specific
      areas of concern, they are limited to gathering information that the researcher
      sees as important. Thus, the value of phenomenology is demonstrated in describing
      the experience as a whole. A problem in using this method is that it can be time
      consuming, hence only seven participants were included in the study. The
      participants were selected on the basis that they had personally lived the
      experience and were willing to participate. Data collection was by means of in
      depth, tape-recorded interviews that were transcribed and analysed. Significant
      statements were extracted from the data and linked to each other to form separate
      themes. The six themes which were identified are described: anticipating fate;
      fear; denial; helplessness; sharing of altered body image; and diversity of
      emotions. Finally, the implications for nursing are discussed.

PMID- 29323599
TI  - Nurses in the front lines of palliative care.
AB  - Nurses generally serve in the front lines of action; this is particularly true
      for those involved in palliative care. Informed nurses are essential around the
      world, especially in developing countries, where 39 of the 51 million individuals
      who die every year are to be found. Nurses are key in the delivery of palliative
      care and are in great need of the sort of timely and readily understandable in
      formation to be provided by the International Journal of Palliative Nursing
      (IJPN).

PMID- 29323601
TI  - After diagnosis of cancer: the patient's view of life.
AB  - This research was undertaken to increase our understanding of cancer patients'
      perceptions of their needs, and how these changed over time. Sixty five patients
      with breast, prostate/testes or colorectal cancer were each interviewed at 5 and
      13 months. Concrete accounts were elicited of good and bad experiences that were
      significant to patients. Three dimensions of need were identified: care
      availability and quality in disease management; good information and sympathetic
      communication; and, most importantly, regaining control of life.

PMID- 29323602
TI  - Macmillan carers: a practical approach to home care.
AB  - This article describes a service development in palliative care which aims to
      offer practical support and caring skills to patients and their families at home.
      The concept of home care in the UK distinguishes between health-care and social
      care needs and workers are allocated from different departments to provide that
      care. Such a distinction is not always clear and there is much debate about how
      needs are split. The continued allocation of funding from separate health and
      social services resources exacerbates the issue. The Macmillan Carer Scheme,
      which offers both health and social care to patients and their families, is an
      important and significant step in the move towards needs-based service
      development.

PMID- 29323603
TI  - Correspondence.
AB  - Madam, Thank you for an excellent second edition of the International journal o f
      Palliative Nursing. I am excited by the development of the journal and eagerly
      await each edition.

PMID- 29323604
TI  - Preconception Health Indicators for Public Health Surveillance.
AB  - OBJECTIVES: In response to an expressed need for more focused measurement of
      preconception health (PCH), we identify a condensed set of PCH indicators for
      state and national surveillance. METHODS: We used a systematic process to
      evaluate, prioritize, and select 10 PCH indicators that maternal and child health
      programs can use for surveillance. For each indicator, we assessed prevalence,
      whether it was addressed by professional recommendations, Healthy People 2020
      objectives, or Centers for Disease Control and Prevention winnable battles,
      measurement simplicity, data completeness, and stakeholders' input. RESULTS:
      Fifty PCH indicators were evaluated and prioritized. The condensed set includes
      indicators that rely on data from the Pregnancy Risk Assessment Monitoring System
      (n = 4) and the Behavioral Risk Factor Surveillance System (n = 6). The content
      encompasses heavy alcohol consumption, depression, diabetes, folic acid intake,
      hypertension, normal weight, recommended physical activity, current smoking,
      unwanted pregnancy, and use of contraception. CONCLUSIONS: Having a condensed set
      of PCH indicators can facilitate surveillance of reproductive-aged women's health
      status that supports monitoring, comparisons, and benchmarking at the state and
      national levels.

PMID- 29323606
TI  - Response to Dr Pedersen's article.

PMID- 29323605
TI  - Outcomes for Gestational Carriers Versus Traditional Surrogates in the United
      States.
AB  - BACKGROUND: Little is known about the obstetric and procedural outcomes of
      traditional surrogates and gestational carriers. MATERIALS AND METHODS:
      Participants included 222 women living in the United States who completed a brief
      online survey between November 2015 and February 2016. Differences between
      gestational carriers (n = 204) and traditional surrogates (n = 18) in demographic
      characteristics, pregnancy outcomes, and procedural outcomes were examined using
      chi-squared tests, Fisher's exact tests, and t-tests. RESULTS: Out of 248
      eligible respondents, 222 surveys were complete, for a response rate of 89.5%.
      Overall, obstetric outcomes were similar among gestational carriers and
      traditional surrogates. Traditional surrogates were more likely than gestational
      carriers to have a Center for Epidemiologic Studies Depression Scale Revised
      score of 16 or higher (37.5% vs. 4.0%). Gestational carriers reported higher mean
      compensation ($27,162.80 vs. $17,070.07) and were more likely to travel over 400
      miles (46.0% vs. 0.0%) than traditional surrogates. CONCLUSIONS: Procedural
      differences, but not differences in obstetric outcomes, emerged between
      gestational carriers and traditional surrogates. To ensure that both traditional
      surrogates and gestational carriers receive optimal medical care, it may be
      necessary to extend practice guidelines to ensure that traditional surrogates are
      offered the same level of care offered to gestational carriers.

PMID- 29323607
TI  - Efficacy of oral vancomycin in primary prevention of Clostridium Difficile
      infection in elderly patients treated with systemic antibiotic therapy.

PMID- 29323608
TI  - The Association Between Low 50 g Glucose Challenge Test Values and Adverse
      Pregnancy Outcomes.
AB  - BACKGROUND: The implications of low values on the 50 g glucose challenge test
      (GCT) in pregnancy are not clearly defined. Few studies have evaluated the
      influence of maternal low GCT values on obstetrical outcomes. This study aimed to
      compare pregnancy outcomes between women with low 50 g GCT values and those with
      normal values. MATERIALS AND METHODS: Women undergoing gestational diabetes
      mellitus screening at 24-28 weeks of gestational age between January 2010 and
      December 2016 were retrospectively evaluated. Women with multifetal pregnancies,
      prepregnancy type I or II diabetes, GCT performed before 24 or after 28 weeks of
      gestational age, and women undergoing multiple GCTs in the same pregnancy were
      excluded. Low GCT values and normal GCT values were defined as <=85 mg/dL and 86
      130 mg/dL, respectively. RESULTS: Of 3875 screened subjects, 519 (13.4%) women
      were included in the low GCT group and 3356 (86.6%) in the normal GCT group. Low
      GCT women had a significantly higher rate of small for gestational age (SGA)
      infants than normal GCT women (10.8% vs. 7.9%, p = 0.02). Cesarean section and
      postpartum hemorrhage (PPH) were less frequent in low GCT women than in normal
      women (32.6% vs. 42.8%, p < 0.01 and 0.2% vs. 1.2%, p = 0.03, respectively). Low
      GCT women had a 1.38-fold increased risk of bearing SGA infants (95% confidence
      intervals: 1.01-1.88, p = 0.04). CONCLUSIONS: Rate of SGA infants was
      significantly higher and cesarean delivery and PPH rates were significantly lower
      in women with low GCT values. Low GCT values were independently associated with
      an increased risk of SGA.

PMID- 29323610
TI  - The Debate About Electronic Cigarettes: Harm Minimization or the Precautionary
      Principle.
AB  - Two contrasting reviews (authored by Abrams et al. and Glantz & Bareham) in this
      volume have reached opposing conclusions on the effects of electronic cigarettes
      in a debate that is dividing the scientific and professional communities that
      have devoted careers to controlling the manufacture, advertising, sale, and use
      of combustible cigarettes. The research on the types, degree, and extent of harm
      from e-cigarettes is far from complete and, together with trends in teenage
      smoking and vaping, has raised new questions and prospects about the potential
      benefits that the new electronic products offer smokers of combustible cigarettes
      in quitting or at least cutting back on the known risks associated with the
      traditional forms of smoking. The rapidly morphing forms, constituents,
      promotions, and uses of the electronic varieties of the new nicotine delivery
      products (in this case electronic cigarettes) make research on their biological
      and behavioral effects moving targets. The two sides of this argument have
      produced a global divide on policy strategies.

PMID- 29323611
TI  - Harm Minimization and Tobacco Control: Reframing Societal Views of Nicotine Use
      to Rapidly Save Lives.
AB  - Inhalation of the toxic smoke produced by combusting tobacco products, primarily
      cigarettes, is the overwhelming cause of tobacco-related disease and death in the
      United States and globally. A diverse class of alternative nicotine delivery
      systems (ANDS) has recently been developed that do not combust tobacco and are
      substantially less harmful than cigarettes. ANDS have the potential to disrupt
      the 120-year dominance of the cigarette and challenge the field on how the
      tobacco pandemic could be reversed if nicotine is decoupled from lethal inhaled
      smoke. ANDS may provide a means to compete with, and even replace, combusted
      cigarette use, saving more lives more rapidly than previously possible. On the
      basis of the scientific evidence on ANDS, we explore benefits and harms to public
      health to guide practice, policy, and regulation. A reframing of societal
      nicotine use through the lens of harm minimization is an extraordinary
      opportunity to enhance the impact of tobacco control efforts.

PMID- 29323612
TI  - Pharmacokinetic Analysis of Intraocular Penetration of Latanoprost Solutions with
      Different Preservatives in Human Eyes.
AB  - PURPOSE: To investigate the effect of excipients on latanoprost penetration into
      the aqueous humor with clinically available 6 products with different solutions
      mainly in the types and concentrations of preservatives. METHODS: In 363 patients
      with cataracts, we instilled 1 latanoprost drop in 1 eye before surgery. The drop
      was randomly selected by brand name product (A) and 5 generic products (B-F)
      composed with different excipients. B contains similar excipients to A. C and D
      contain lower concentrations of benzalkonium chloride than A. E includes sodium
      benzoate, and F contains no preservatives. At 0.5-1, 3, and 6 h after
      instillation, samples of aqueous humor were collected to determine the
      latanoprost free acid by mass spectrometry. The time course of intraocular
      concentration and the areas under the aqueous humor latanoprost free acid
      concentration-time curves (AUCs) were calculated. RESULTS: At 0.5-1 h, the
      aqueous humor concentration of latanoprost free acid was 8.5 +/- 1.0 ng/mL for C,
      which was significantly higher (P < 0.01) than that of A (3.4 +/- 0.5 ng/mL). At
      3 and 6 h, however, no significant difference was noted in the concentrations of
      latanoprost free acid between the brand name and generic products. For each of
      the generic products, the peak free acid concentration was above the known
      threshold concentration for biological activity. At 6 h postdose, however, the
      levels of latanoprost free acid were below the threshold for Products C, E, and
      F. Comparisons of AUC0-6h and AUC0-24h values showed that these parameters were
      the greatest with A, and E was significantly inferior to A (P < 0.05).
      CONCLUSIONS: Currently available latanoprost solutions with different
      preservatives showed sufficient intraocular concentration to activate the FP
      receptor, but different pharmacokinetic profiles of absorption or elimination.

PMID- 29323609
TI  - E-Cigarettes: Use, Effects on Smoking, Risks, and Policy Implications.
AB  - Since e-cigarettes appeared in the mid-2000s, some practitioners, researchers,
      and policy makers have embraced them as a safer alternative to conventional
      cigarettes and an effective way to stop smoking. While e-cigarettes deliver lower
      levels of carcinogens than do conventional cigarettes, they still expose users to
      high levels of ultrafine particles and other toxins that may substantially
      increase cardiovascular and noncancer lung disease risks, which account for more
      than half of all smoking-caused deaths, at rates similar to conventional
      cigarettes. Moreover, rather than stimulating smokers to switch from conventional
      cigarettes to less dangerous e-cigarettes or quitting altogether, e-cigarettes
      are reducing smoking cessation rates and expanding the nicotine market by
      attracting youth.

PMID- 29323613
TI  - iDrugs and iDevices Discovery Research: Preclinical Assays, Techniques, and
      Animal Model Studies for Ocular Hypotensives and Neuroprotectants.
AB  - Discovery ophthalmic research is centered around delineating the molecular and
      cellular basis of ocular diseases and finding and exploiting molecular and
      genetic pathways associated with them. From such studies it is possible to
      determine suitable intervention points to address the disease process and
      hopefully to discover therapeutics to treat them. An investigational new drug
      (IND) filing for a new small-molecule drug, peptide, antibody, genetic treatment,
      or a device with global health authorities requires a number of preclinical
      studies to provide necessary safety and efficacy data. Specific regulatory
      elements needed for such IND-enabling studies are beyond the scope of this
      article. However, to enhance the overall data packages for such entities and
      permit high-quality foundation-building publications for medical affairs,
      additional research and development studies are always desirable. This review
      aims to provide examples of some target localization/verification, ocular drug
      discovery processes, and mechanistic and portfolio-enhancing exploratory
      investigations for candidate drugs and devices for the treatment of ocular
      hypertension and glaucomatous optic neuropathy (neurodegeneration of retinal
      ganglion cells and their axons). Examples of compound screening assays, use of
      various technologies and techniques, deployment of animal models, and data
      obtained from such studies are also presented.

PMID- 29323614
TI  - Evaluation of anionic surfactants effects on the skin barrier function based on
      skin permeability.
AB  - Anionic surfactants are often used for cleaning and pharmaceutical purposes
      because of their strong surfactancy and foaming property. However, they are
      rarely ingested orally, the skin is a part of the human body most affected by
      surfactants. Barrier function of the skin is very strong, but the anionic
      surfactants can cause serious damages to it. Recently, amino acid-based
      surfactants have attracted attention as a safer option owing to their
      biocompatibility. Cytotoxicity examinations revealed that the amino acid-based
      surfactants are superior to sulfate-based surfactants. However, a systematical
      and comprehensive study related to the effect of these surfactants on skin
      barrier function has not yet been reported. In this work, skin permeation test
      using the skin of hairless mice and HPLC method is carried out. The material
      transmission speed through skin in a steady state was different between each
      surfactant treatment. We performed a comprehensive analysis of the effect of
      surfactants on skin barrier function and defined Transmission Index as an index
      for the degree of effect of surfactants. Glutamate series amino acid-based
      surfactant were effective to Transmission Index and we guessed the cause was due
      to adsorption. Based on the finding this study, we suggest using adsorptive
      property as a measure to the effect on the skin barrier function.

PMID- 29323615
TI  - Short-Term and Long-Term Outcomes of Laparoscopic Versus Open Surgery for Low
      Rectal Cancer.
AB  - AIM: To compare the short-term and long-term outcomes of laparoscopic versus open
      surgery for low rectal cancer. METHODS: Patients with low rectal cancer who
      underwent laparoscopic or open surgery at our department from January 2009 to
      December 2013 were enrolled in this retrospective study. The primary end points
      were 3-year local recurrence and overall and disease-free survival (DFS) rates.
      Secondary end points were intraoperative and postoperative outcomes. RESULTS:
      Laparoscopic group had longer operative time (165.0 versus 140.0, P < .001), less
      blood loss (20.0 versus 40.0, P < .001), shorter length of incision (5.0 versus
      18.0, P < .001), and more lymph node harvested (11.0 versus 9.0, P = .002).
      However, time to first flatus (P = .941), postoperative hospital stay (P = .095),
      postoperative complications (P = .155), and 30-day mortality (P = .683) was
      similar between two groups. With the median follow-up period of 65 months, the 3
      year local recurrence rate was 4.3% in laparoscopic group and 7.5% in open group
      (P = .077); the 3-year overall and DFS rates were similar in two groups (85.9%
      versus 88.8%, P = .229 and 76.9% versus 79.2%, P = .448, respectively); and the
      overall and DFS curves were comparable between two groups (hazard ratio [HR] =
      0.858, 95% confidence intervals [CI] 0.709-1.037, P = .112 and HR = 1.076, 95% CI
      0.834-1.389, P = .275, respectively). CONCLUSIONS: Laparoscopic surgery is safe
      and has equivalent long-term oncologic outcomes for low rectal cancer when
      compared to open surgery. Furthermore, large-scale, prospective randomized
      clinical trials are needed to confirm the present findings.

PMID- 29323616
TI  - Bipolar Energy Instruments in Laparoscopic Uterine Cancer Surgery: A Randomized
      Study.
AB  - OBJECTIVE: To compare the perioperative outcomes of patients with uterine cancer,
      who were operated using advanced or conventional bipolar instruments. MATERIALS
      AND METHODS: Patients with clinically early-stage endometrial cancer were
      randomized to advanced (LigaSure) or conventional (Robi forceps) bipolar groups.
      Surgeries were performed by laparoscopy. Hysterectomy and bilateral salpingo
      oophorectomy with retroperitoneal lymphadenectomy were done in all cases. Primary
      endpoint of the study was to compare operation time for 2 groups. Other
      perioperative outcomes were also compared. ClinicalTrials.gov identifier number
      of the study was NCT02822820. RESULTS: Sixty-eight cases with endometrial cancer
      were randomized to 2 groups and each group included 34 subjects. Mean age and
      body mass index of all cases were 56.8 +/- 10.4 years and 31.1 +/- 5.3 kg/m2,
      respectively. Mean operation time was found significantly shorter in advanced
      bipolar group (134.2 +/- 29.7 minutes versus 163.5 +/- 27.7 minutes, P < .001).
      The other variables investigated such as intraoperative blood loss, duration of
      hospital stay, and postoperative pain scores did not show statistically
      significant difference between the groups. CONCLUSION: Operation time was shorter
      in advanced bipolar group, however, advanced and conventional bipolar energy
      instruments were comparable for other perioperative outcomes in laparoscopic
      endometrial cancer surgery.

PMID- 29323617
TI  - Differential effects of early palliative care based on the age and sex of
      patients with advanced cancer from a randomized controlled trial.
AB  - BACKGROUND: Early palliative care interventions enhance patient outcomes,
      including quality of life, mood, and coping, but it remains unclear whether
      certain subgroups of patients are more likely to benefit from early palliative
      care. We explored whether age and sex moderate the improved outcomes seen with
      early palliative care. METHODS: We performed a secondary analysis of data from a
      randomized trial of 350 patients with advanced lung and non-colorectal
      gastrointestinal cancer. Patients received an early palliative care intervention
      integrated with oncology care or usual oncology care alone. We used linear
      regression to determine if age (older or younger than 65) and sex moderated the
      effects of the intervention on quality of life (Functional Assessment of Cancer
      Therapy-General (FACT-G)), depression symptoms (Patient Health Questionnaire 9
      (PHQ-9)), and coping (Brief COPE) within lung and gastrointestinal subgroups.
      RESULTS: At 24 weeks, younger patients with lung cancer receiving early
      palliative care reported increased use of active coping ( B = 1.74; p = 0.02) and
      decreased use of avoidant coping ( B = -0.97; p = 0.02), but the effects of early
      palliative care on these outcomes were not significant for older patients. Male
      patients with lung cancer assigned to early palliative care reported better
      quality of life (FACT-G: B = 9.31; p = 0.01) and lower depression scores (PHQ-9:
      B = -2.82; p = 0.02), but the effects of early palliative care on these outcomes
      were not significant for female patients. At 24 weeks, we found no age or sex
      moderation effects within the gastrointestinal cancer subgroup. CONCLUSION: Age
      and sex moderate the effects of early palliative care for patients with advanced
      lung cancer. Early palliative care may need to be tailored to individuals' unique
      sociodemographic and clinical characteristics.

PMID- 29323618
TI  - Measuring attitudes towards the dying process: A systematic review of tools.
AB  - BACKGROUND: At the end of life, anxious attitudes concerning the dying process
      are common in patients in Palliative Care. Measurement tools can identify
      vulnerabilities, resources and the need for subsequent treatment to relieve
      suffering and support well-being. AIM: To systematically review available tools
      measuring attitudes towards dying, their operationalization, the method of
      measurement and the methodological quality including generalizability to
      different contexts. DESIGN: Systematic review according to the PRISMA Statement.
      Methodological quality of tools assessed by standardized review criteria. DATA
      SOURCES: MEDLINE, PsycINFO, PsyndexTests and the Health and Psychosocial
      Instruments were searched from their inception to April 2017. RESULTS: A total of
      94 identified studies reported the development and/or validation of 44 tools. Of
      these, 37 were questionnaires and 7 alternative measurement methods (e.g.
      projective measures). In 34 of 37 questionnaires, the emotional evaluation (e.g.
      anxiety) towards dying is measured. Dying is operationalized in general items ( n
      = 20), in several specific aspects of dying ( n = 34) and as dying of others ( n
      = 14). Methodological quality of tools was reported inconsistently. Nine tools
      reported good internal consistency. Of 37 tools, 4 were validated in a clinical
      sample (e.g. terminal cancer; Huntington disease), indicating questionable
      generalizability to clinical contexts for most tools. CONCLUSION: Many tools
      exist to measure attitudes towards the dying process using different endpoints.
      This overview can serve as decision framework on which tool to apply in which
      contexts. For clinical application, only few tools were available. Further
      validation of existing tools and potential alternative methods in various
      populations is needed.

PMID- 29323619
TI  - RNF8 - The Achilles heel of DNA repair when splicing rules.

PMID- 29323620
TI  - Enhanced visible light photocatalytic activity of N, F-codoped TiO2 powders with
      high thermal stability.
AB  - Doping non-metals onto TiO2 has been regarded as a promising way to gain a more
      effective photocatalyst. In this paper, N, F-codoped TiO2 was synthesized by the
      sol-gel method, demonstrating both high adsorption capacity and high
      photocatalytic activity under visible light irradiation. Samples were
      characterized by X-ray diffraction, scanning electron microscopy (SEM), X-ray
      photoelectron spectroscopy and UV-visible diffuse reflectance spectra (UV-vis
      DRS). The results show that N, F-codoping can reduce the impact of calcination
      temperature on the structure and morphology of the sample, resulting in the
      sample exhibiting good thermal stability, even when the calcination temperature
      changes in a large range, instead of rutile, the anatase around 20 nm is the only
      phase in N, F-codoped samples. It can be clearly observed from the SEM images
      that N, F-codoped samples calcined at different temperatures are in the state of
      scattered particles with small size and good dispersed property. And it is vivid
      that the absorption intensity of N, F-codoped TiO2 samples in the visible light
      range increases substantially in DRS. According to the result of photocatalytic
      activity experiment, N, F-codoped TiO2 samples calcined at 973 K exhibited the
      highest degradation rate for Methylene Blue.

PMID- 29323622
TI  - Enhancing health care professionals' and trainees' knowledge of physical activity
      guidelines for adults with and without SCI.
AB  - BACKGROUND: Health care providers (HCPs) are preferred sources of physical
      activity (PA) information; however, minimal research has explored HCPs' knowledge
      of spinal cord injury (SCI) PA guidelines, and no research has examined HCP
      trainees' PA guideline knowledge. OBJECTIVE: The current study explored HCPs' and
      trainees' initial knowledge of PA guidelines for both adults with SCI and the
      general population, and the utility of an event-based intervention for improving
      this knowledge. METHODS: Participants (HCPs n = 129; trainees n = 573) reported
      guideline knowledge for both sets of guidelines (SCI and general population)
      immediately after, one-month, and six-months following the intervention.
      Frequencies determined guideline knowledge at each timepoint, while chi-squared
      tests examined differences in knowledge of both guidelines, as well as knowledge
      differences in the short- and long-term. RESULTS: Results demonstrated that HCPs
      and trainees lack knowledge of PA guidelines, particularly guidelines for adults
      with SCI. The results further suggest that a single event-based intervention is
      not effective for improving long-term guideline knowledge. CONCLUSION:
      Suggestions are made for future research with the aim of improving interventions
      that target HCP and HCP trainees' long-term guideline knowledge for adults with
      SCI and the general population.

PMID- 29323623
TI  - Bladder management practices in spinal cord injury patients: A single center
      experience from a developing country.
AB  - CONTEXT/OBJECTIVE: Inadequate bladder management in spinal cord injury (SCI)
      patients results in significant morbidity and even mortality. Clean intermittent
      catheterization (CIC) is the recommended option for SCI patients. The objective
      of the study was to document the bladder management practices of SCI patients in
      a developing country. DESIGN: Questionnaire based cross sectional survey Setting:
      Armed Forces Institute of Rehabilitation Medicine, Rawalpindi, Pakistan
      Participants: All patients with SCI (irrespective of duration, level and
      etiology) Interventions: Data documentation included demographics, level,
      severity and time since injury, bladder management techniques used, details of
      CIC, results of Urodynamic studies (if available), complications resulting from
      bladder management technique and patient awareness of the yearly follow up. SPSS
      V 20 was used for analysis. OUTCOME MEASURES: Not applicable Results: Thirty four
      consenting patients were enrolled. All were males. Mean age was 31.24 +/- 10.9.
      Most (17) of the patients were thoracic level paraplegics, while 12 patients had
      sustained a cervical SCI. Majority (23) had complete injury (ASIA A). Fifteen
      patients used CIC for bladder management followed by in dwelling Foley catheters
      in thirteen patients Those using CIC performed the procedure every four hours and
      used disposable catheters. The same 'disposable' catheter was used for 5-7 days
      by half of these patients. Only Six patients independently performed CIC. Three
      patients on CIC reported urinary tract infection. CONCLUSIONS: In the largest
      spinal rehabilitation unit of a developing country; Pakistan CIC was the
      preferred method of bladder management followed by indwelling catheter. Re-use of
      disposable catheters is a common practice due to cost issues. The rate of UTI was
      significantly lower in patients on CIC.

PMID- 29323621
TI  - Vaccines for the Paramyxoviruses and Pneumoviruses: Successes, Candidates, and
      Hurdles.
AB  - Human parainfluenza viruses (family Paramyxoviridae), human metapneumovirus, and
      respiratory syncytial virus (family Pneumoviridae) infect most infants and
      children within the first few years of life and are the etiologic agents for many
      serious acute respiratory illnesses. These virus infections are also associated
      with long-term diseases that impact quality of life, including asthma. Despite
      over a half-century of vaccine research, development, and clinical trials, no
      vaccine has been licensed to date for the paramyxoviruses or pneumoviruses for
      the youngest infants. In this study, we describe the recent reclassification of
      paramyxoviruses and pneumoviruses into distinct families by the International
      Committee on the Taxonomy of Viruses. We also discuss some past unsuccessful
      vaccine trials and some currently preferred vaccine strategies. Finally, we
      discuss hurdles that must be overcome to support successful respiratory virus
      vaccine development for the youngest children.

PMID- 29323624
TI  - Sella turcica bridging and ossified carotico-clinoid ligament: Correlation with
      sex and age.
AB  - Aim Sella turcica bridging and ossified carotico-clinoid ligament are two
      variants of the sella turcica, the origin of which is partially unknown. These
      variations should be properly recognised, as they may hamper the removal of the
      anterior clinoid process in surgical procedures. Therefore, our aim was to
      determine the prevalence of these two anatomical variants and to investigate
      their prevalence according to patient sex and age in a series of maxilla computed
      tomography scans. Materials and methods We revised 300 computed tomography scans
      of the head from northern Italian patients, stratified into three age groups (18
      40 years, 41-60 years, >60 years): a logistic regression analysis was used to
      explore an association of sella turcica bridging with age and sex through Matlab
      software, also including a test for the extracted model ( P < 0.05). Results The
      mean prevalence of sella turcica bridging and ossified carotico-clinoid ligament
      were 0.16 +/- 0.06 (48/300, 16.0%) and 0.09 +/- 0.03 (26/300, 8.7%),
      respectively. Statistically significant differences according to sex were found
      neither for sella turcica bridging ( P = 0.345) nor for ossified carotico-clinoid
      ligament ( P = 0.412). Only sella turcica bridging showed a correlation with age
      ( P = 0.007). In addition, the two variants were often associated, as patients
      without sella turcica bridging usually did not show ossified carotico-clinoid
      ligament ( P < 0.001). Discussion Our results suggest an association between the
      two variants, and provide a novel contribution to the debate around their origin.

PMID- 29323626
TI  - A Scenario-Based Cognitive Behavioral Therapy Mobile App to Reduce Dysfunctional
      Beliefs in Individuals with Depression: A Randomized Controlled Trial.
AB  - INTRODUCTION: While self-administered mobile app-based cognitive behavioral
      therapy (CBT) has shown efficiency and effectiveness over the past decade,
      attempts to address automatic and negative beliefs have been lacking. The purpose
      of this study was to introduce and verify a mobile app that directly intervenes
      in dysfunctional thoughts. This app-based treatment includes recognizing
      automatic and negative thoughts of the protagonist of scenarios, writing advice
      directly to the main character, and sharing advice provided by other
      participants. MATERIALS AND METHODS: Thirty-four participants diagnosed with
      Other Specified Depressive Disorder were recruited and randomly allocated to a
      CBT-based mobile-app program, the Todac Todac (TT group), or a daily mood chart
      app program (control group). Participants were asked to use the software for 3
      weeks. Assessments for autonomic thoughts and clinical symptoms were administered
      at baseline and at a follow-up evaluation. RESULTS: After completing the 3-week
      program, Dysfunctional Attitude Scale (DAS) scores in TT group were lower than
      they were in the control group. In clinical measures, both TT group and control
      group showed reduced Beck Depression Inventory-II (BDI-II) scores and situation
      dependent trait version of State-Trait Anxiety Inventory (STAI-X2) at follow-up.
      However, TT group showed significantly reduced STAI-X2 scores compared to control
      group. For all participants, changes in DAS scores were correlated with BDI-II
      and STAI-X2 scores. CONCLUSIONS: Our preliminary findings provide promising
      evidence that scenario-based CBT mobile apps can be used to deliver feasible and
      efficacious cognitive therapy. Long-term research is needed to determine the
      impact and effectiveness of this new treatment format.

PMID- 29323625
TI  - Catheter-associated urinary tract infections in persons with neurogenic bladders.
AB  - This review is based on the author's Donald Munro Lecture given at the annual
      conference of the Academy of Spinal Cord Injury Professionals in New Orleans, LA.
      Indwelling catheters play an important role in bladder management following SCI
      for many individuals with neurogenic bladders. There is an increased risk of UTI
      compared to other types of bladder management with indwelling urethral catheters
      but not SP catheters. To minimize the risk of symptomatic UTI, the following
      steps are essential: prevent bladder wall distention and resulting ischemia,
      maintain colonization with "good" bacteria, and prevent bladder stones. For
      individuals with recurrent symptomatic UTIs, try to change the environment,
      prevent bladder over distention, and make sure the bladder is "quiet" by using
      strategies such as adequate dosages of anticholinergics, onabotulinum toxin A,
      and preventing catheter blockage. Bacterial colonization of the bladder is
      common. However, bacterial colonization may have a positive effect by inhibition
      of colonization of pathogenic bacteria. Judicious use of antibiotics is important
      since antibiotics hasten the evolution of more resistant organisms. Potential
      prevention and treatment strategies include killing the offending organisms,
      changing the environment (such as urinary acidification), and modifying virulence
      factors and the bacterial microbiome.

PMID- 29323627
TI  - A Phase 3, Multicenter, Prospective, Open-Label Study to Evaluate the Safety of a
      Single Dose of Secnidazole 2 g for the Treatment of Women and Postmenarchal
      Adolescent Girls with Bacterial Vaginosis.
AB  - BACKGROUND: A novel formulation of secnidazole is under development in the United
      States for the treatment of bacterial vaginosis (BV). Efficacy and safety of
      other formulations of secnidazole have been reported. The objective of this study
      is to evaluate the safety of a single-dose oral granule formulation of
      secnidazole in a U.S. population of women with BV. METHODS: In this open-label
      study, patients were enrolled based on the following criteria: off-white, thin,
      homogeneous vaginal discharge; vaginal pH >=4.7; presence of >=20% clue cells;
      and positive potassium hydroxide whiff test. Eligible patients received a single
      dose of secnidazole 2 g at baseline. Patients were contacted on days 8-10 and
      were assessed for safety at an end-of-study visit (days 21-30). Additional
      endpoints included investigator assessment of the need for additional treatment
      and a post hoc analysis of clinical response to treatment. RESULTS: Of 321
      patients, 283 (88.2%) completed the study. The mean age was 32 +/- 8.5 years;
      most patients were white (51.4%) or black/African American (46.1%). Most (79.1%)
      reported <=3 episodes of BV in the past year. The overall number of treatment
      emergent adverse events (TEAEs) was 95 (29.6%), of which 53 (16.5%) were
      treatment related. Common treatment-related TEAEs were vulvovaginal mycotic
      infection (5.3%), nausea (4.4%), and dysgeusia (3.1%). The proportion of patients
      not requiring additional BV treatment, as assessed by investigators, was 72.5%.
      CONCLUSIONS: Single-dose secnidazole 2 g was well tolerated, with a low overall
      number of TEAEs, most of which were mild to moderate.

PMID- 29323628
TI  - Use of Telehealth as a New Model for Following Intermittent Claudication and
      Promoting Patient Expertise.
AB  - BACKGROUND: A change in healthcare systems is needed, due to the increased
      prevalence of chronic diseases. Patient empowerment improves results in terms of
      patient quality of life (QoL) and satisfaction. INTRODUCTION: We have developed a
      telehealth program Control Telehealth Claudication Intermittent (CONTECI) for
      patients with peripheral arterial disease (PAD), aimed at enhancing patient
      satisfaction and QoL, while improving health system efficiency. MATERIALS AND
      METHODS: We conducted a randomized clinical trial of patients with PAD, at the
      intermittent claudication stage. Study subjects were randomized into either (1)
      an intervention arm (IA), which utilized our CONTECI program for promoting
      patient self-management, or (2) a control arm (CA), utilizing the familiar system
      of in-person patient visits. All patients were followed up at 1 year. RESULTS:
      The trial included 150 patients, 75 in each arm. Complications were diagnosed
      more quickly in the IA (7.85 days standard deviation (SD) 9.95 vs. 53.89 days SD
      41.56; p = 0.016) compared with the CA. Rest pain decreased (1.4% vs. 8.4%; p =
      0.05) in the IA group, as did the number of scheduled visits-decreased by 95.95%
      and the number of emergency visits (p = 0.017). QoL scores in IA patients
      improved from baseline (67.87 vs. 72.25; p = 0.047), as did patient satisfaction
      (67.36 vs. 76.78; p = 0.03). DISCUSSION: Telemedicine can improve health results
      and aid communication and visit scheduling. Our e-Health programs are financially
      viable. CONCLUSIONS: Self-management using the CONTECI telehealth program is
      feasible for patients with PAD. The program promotes patient expertise,
      encourages proactivity, increases QoL and satisfaction with disease control, and
      improves health resource use, with no evidence of clinical inferiority to
      conventional practices.

PMID- 29323629
TI  - RETRACTED: Three-Minutes Sitting Test for evaluating lumbar foraminal stenosis: A
      preliminary report.
AB  - This article has been retracted.

PMID- 29323630
TI  - Fatal innominate artery hemorrhage in a patient with tetraplegia: Case report and
      literature review.
AB  - Context Hemorrhage is one of the potentially fatal complications of tracheostomy.
      A rare but lethal cause of tracheostomy related bleeding is hemorrhage from the
      innominate artery. This occurs following tracheo-innominate artery fistula (TIF)
      formation, which is associated with a mortality rate of more than 85%. Here, we
      report the case of an individual with tetraplegia and a tracheostomy who died as
      a result of innominate artery hemorrhage. This case highlights the possible
      causes and interventions associated with this complication, and provides insight
      into tracheostomy related bleeding in patients with spinal cord injury (SCI).
      Findings A 15-year-old boy with a diagnosis of incomplete SCI at the C5 level was
      admitted for rehabilitation 4 months after injury. He required a tracheostomy for
      ventilation, and underwent subglottic stenosis dilatation thrice. Multiple
      decannulation attempts were performed without success. He received intensive care
      on several occasions for respiratory failure. During the course of his
      rehabilitation, a minimal tracheostomy bleed was observed, which became profuse
      within a few hours and led to hypoxia with loss of consciousness. An urgent
      sternotomy identified bleeding from a TIF. He suffered severe brain damage
      following massive tracheal hemorrhage and died. Conclusion/clinical relevance
      Given the morbidity of TIF-related hemorrhage, it is important to increase
      awareness of this rare condition among health-care providers, especially those in
      non-acute settings. Patients with SCI and a tracheostomy pose unique challenges
      related to respiratory compromise, which may accentuate TIF formation.

PMID- 29323631
TI  - Endovascular treatment with tirofiban during the acute stage of cervical spinal
      cord infarction due to vertebral artery dissection.
AB  - CONTEXT: Cervical spinal cord infarction is a rare and severe complication of
      vertebral artery dissection (VAD). We report a case of VAD in an acute stage
      followed by cervical spinal cord infarction that was treated using direct
      endovascular tirofiban infusion via digital subtraction angiography (DSA)
      monitoring. FINDINGS: A 48-year-old man presented with vertigo, neck pain,
      numbness and weakness in four limbs with subsequent cardiac and respiratory
      arrest. Neurological examination revealed hypoesthesia below the neck with grade
      one myodynamia on the right side of the limbs and zero on the left side. The
      diagnosis of VAD-related cervical spinal infarction was confirmed using DSA
      imaging and cervical vertebra magnetic resonance imaging (MRI). The patient
      received timely treatment with endovascular tirofiban infusion and achieved good
      outcome without any sequelae. CONCLUSION: Endovascular treatment with tirofiban
      may be a selective choice for cervical spinal cord infarction due to VAD in acute
      stage and warrants further study.

PMID- 29323632
TI  - Recycling of neodymium enhanced by functionalized magnetic ferrite.
AB  - This study systematically evaluates Neodymium (Nd) recovery from actual seawaters
      and wastewater using functionalized magnetic ferrite (3-mercaptopropionic acid
      tetraethyl orthosilicate ferrite, MPA-TEOS-ferrite). The recovery of Nd by MPA
      TEOS-ferrite displayed an L-shaped nonlinear isotherm, suggesting limiting
      binding sites on the adsorbent surface. At room temperature, a significant
      recovery of Nd by MPA-TEOS-ferrite increased from 8.99% to 99.99% with increasing
      pH (2.89-8.16) and an enhanced maxima Nd recovery capacity was observed on MPA
      TEOS-ferrite (25.58 mg/g) when compared with pure ferrite (22.27 mg/g). The L3
      edge X-ray absorption near-edge structure (XANES) spectra for the adsorbents
      collected after Nd recovery indicated that Nd(III) was still the predominant
      oxidation species on the surface of MPA-TEOS-ferrite. Only slightly change in the
      oxidation state or electronic structure around the Nd ions could be found during
      the adsorption process. Importantly, no significant change was found on Nd
      recovery while the NaCl ionic strength increased from 0.01 to 0.5 N. Furthermore,
      the results also displayed that the synthesized MPA-TEOS-ferrite has a great
      potential in efficient and rapid recovery of Nd from seawaters and wastewater.

PMID- 29323633
TI  - Prevalence of metabolic syndrome in veterans with spinal cord injury.
AB  - CONTEXT/OBJECTIVE: Recent literature would suggest the prevalence of metabolic
      syndrome in persons with spinal cord injury (SCI) is higher than that of the
      general population, although no large cohorts have yet been reported. Part of the
      controversy relates to the differing definitions provided for metabolic syndrome
      and the characterization of obesity in persons with SCI. DESIGN/PARTICIPANTS: The
      current retrospective investigation represents a cross-sectional cohort of 473
      veterans with SCI from a single center in the mid-Atlantic region of the United
      States for whom modified International Diabetes Federation (IDF) criterion
      variables for the metabolic syndrome were available in the computerized personal
      record system (CPRS). OUTCOME MEASURES: These variables included a surrogate
      marker of obesity appropriate to SCI (Body Mass Index (BMI) >= 22 kg/m2), as well
      as indicators of diabetes, dyslipidemia and hypertension. RESULTS: Over 57% of
      the veterans assessed were determined to have metabolic syndrome by modified IDF
      criteria, including 76.7% with BMI >= 22 kg/m2, 55.1% with or under treatment for
      hypertension, 49.7% with or previously diagnosed with diabetes mellitus, and
      69.7% with or under treatment for high density lipoprotein (HDL) cholesterol
      under 40 mg/dl. CONCLUSION: Metabolic syndrome and its constituent components
      appear to be more prevalent in veterans with SCI than in the general population,
      suggesting a greater need for identification and treatment interventions in this
      specialty population.

PMID- 29323634
TI  - Epidemiology of traumatic spinal cord injury in Tianjin, China: An 18-year
      retrospective study of 735 cases.
AB  - STUDY DESIGN: Hospital-based retrospective study Objectives: To evaluate the
      pathogenetic features of traumatic spinal cord injury (TSCI) during 1999-2016
      according to changed injury etiology with time, explore different characteristics
      of patients suffered a TSCI during 1999-2007 and 2008-2016 in Tianjin, China.
      SETTING: Tianjin Medical University General Hospital Methods: In this study, the
      medical records of TSCI patients were obtained from Tianjin Medical University
      General Hospital (TMUGH) from 1st January 1999 to 31th December 2016. Variables
      were recorded, including age, gender occupation, etiology, the level of injury,
      America Spinal Injury Association (ASIA) impairment scale, the severity,
      concomitant injuries, death and its cause. To explore the differences in
      characteristics by etiology and by two periods, related statistical methods were
      used to calculate the correlation of some variables. Differences in etiology of
      TSCI during 1999-2016 were evaluated and differences in epidemiological
      characteristics were separately compared and analyzed between the 1999-2007
      period and the 2008-2016 period. RESULTS: From 1999-2016, 831 TSCI cases were
      identified and 96 cases were excluded from analyses. The male-to-female ratio was
      2.9:1 and the mean age was 49.7+/-15.2 years, which changed significantly between
      1999-2007 (45.1+/-14.2) and 2008-2016 (51.6+/-15.2). Traffic accidents (45.8%)
      were the leading cause of TSCI during the 1999-2007 period, followed by low falls
      (30.7%). However, the opposite result was observed during the 2008-2016 period.
      Significant difference was observed compared with thoracic, lumbar and sacral
      levels, cervical level was the most commonly affected levels and the percentage
      decreased to a certain degree between 1999-2007 and 2008-2016 (from 84.4% to
      68.9%). The proportions of ASIA grades A, B, C, and D were 20.5%, 10.3%, 23.3%,
      and 45.9%, respectively. The percentage of complete tetraplegia decreased from
      22.9% in 1999-2007 to 13.2% in 2008-2016, and the percentage of incomplete
      paraplegia increased from 9.7% to 27.9%. CONCLUSION: According to the changes in
      the epidemiological characteristics of TSCI, relevant health service, laws and
      regulations, preventative strategies should be readjusted to follow up the
      changing situation and epidemiological characteristics of TSCI.

PMID- 29323635
TI  - MukB ATPases are regulated independently by the N- and C-terminal domains of MukF
      kleisin.
AB  - The Escherichia coli SMC complex, MukBEF, acts in chromosome segregation. MukBEF
      shares the distinctive architecture of other SMC complexes, with one prominent
      difference; unlike other kleisins, MukF forms dimers through its N-terminal
      domain. We show that a 4-helix bundle adjacent to the MukF dimerisation domain
      interacts functionally with the MukB coiled-coiled 'neck' adjacent to the ATPase
      head. We propose that this interaction leads to an asymmetric tripartite complex,
      as in other SMC complexes. Since MukF dimerisation is preserved during this
      interaction, MukF directs the formation of dimer of dimer MukBEF complexes,
      observed previously in vivo. The MukF N- and C-terminal domains stimulate MukB
      ATPase independently and additively. We demonstrate that impairment of the MukF
      interaction with MukB in vivo leads to ATP hydrolysis-dependent release of MukBEF
      complexes from chromosomes.

PMID- 29323636
TI  - An optimized method for 3D fluorescence co-localization applied to human
      kinetochore protein architecture.
AB  - Two-color fluorescence co-localization in 3D (three-dimension) has the potential
      to achieve accurate measurements at the nanometer length scale. Here, we
      optimized a 3D fluorescence co-localization method that uses mean values for
      chromatic aberration correction to yield the mean separation with ~10 nm accuracy
      between green and red fluorescently labeled protein epitopes within single human
      kinetochores. Accuracy depended critically on achieving small standard deviations
      in fluorescence centroid determination, chromatic aberration across the
      measurement field, and coverslip thickness. Computer simulations showed that
      large standard deviations in these parameters significantly increase 3D
      measurements from their true values. Our 3D results show that at metaphase, the
      protein linkage between CENP-A within the inner kinetochore and the microtubule
      binding domain of the Ndc80 complex within the outer kinetochore is on average
      ~90 nm. The Ndc80 complex appears fully extended at metaphase and exhibits the
      same subunit structure in vivo as found in vitro by crystallography.

PMID- 29323638
TI  - The NHS at 70 and Alma-Ata at 40.

PMID- 29323637
TI  - Autocatalytic microtubule nucleation determines the size and mass of Xenopus
      laevis egg extract spindles.
AB  - Regulation of size and growth is a fundamental problem in biology. A prominent
      example is the formation of the mitotic spindle, where protein concentration
      gradients around chromosomes are thought to regulate spindle growth by
      controlling microtubule nucleation. Previous evidence suggests that microtubules
      nucleate throughout the spindle structure. However, the mechanisms underlying
      microtubule nucleation and its spatial regulation are still unclear. Here, we
      developed an assay based on laser ablation to directly probe microtubule
      nucleation events in Xenopus laevis egg extracts. Combining this method with
      theory and quantitative microscopy, we show that the size of a spindle is
      controlled by autocatalytic growth of microtubules, driven by microtubule
      stimulated microtubule nucleation. The autocatalytic activity of this nucleation
      system is spatially regulated by the limiting amounts of active microtubule
      nucleators, which decrease with distance from the chromosomes. This mechanism
      provides an upper limit to spindle size even when resources are not limiting.

PMID- 29323640
TI  - Offline: From 1918 to 2018-the lessons of influenza.

PMID- 29323639
TI  - The polio endgame: securing a world free of all polioviruses.

PMID- 29323641
TI  - Syria: 7 years into a civil war.

PMID- 29323642
TI  - Zimbabwe post-Mugabe era: reconstructing a health system.

PMID- 29323643
TI  - Tuberculosis: criteria for global leadership?

PMID- 29323644
TI  - Vision quest: gene therapy for inherited vision loss.

PMID- 29323645
TI  - In search of a teacher.

PMID- 29323646
TI  - WHO washes its hands of older people.

PMID- 29323647
TI  - Another perspective on the Foundation for a Smoke-Free World.

PMID- 29323648
TI  - Targeted radiotherapy for early breast cancer.

PMID- 29323649
TI  - Reducing childhood obesity in the UK and France.

PMID- 29323650
TI  - Reducing childhood obesity in the UK.

PMID- 29323651
TI  - Targeted radiotherapy for early breast cancer - Authors' reply.

PMID- 29323652
TI  - How does azithromycin improve asthma exacerbations? - Author's reply.

PMID- 29323653
TI  - How does azithromycin improve asthma exacerbations?

PMID- 29323654
TI  - Hypothyroidism and hypertension: fact or myth?

PMID- 29323655
TI  - Hypothyroidism and hypertension: fact or myth? - Authors' reply.

PMID- 29323656
TI  - Department of Error.

PMID- 29323657
TI  - Renewing the focus on health care for sexually assaulted children and
      adolescents.

PMID- 29323659
TI  - Production, deformation and mechanical investigation of magnetic alginate
      capsules.
AB  - In this article we investigated the deformation of alginate capsules in magnetic
      fields. The sensitivity to magnetic forces was realised by encapsulating an oil
      in water emulsion, where the oil droplets contained dispersed magnetic
      nanoparticles. We solved calcium ions in the aqueous emulsion phase, which act as
      crosslinking compounds for forming thin layers of alginate membranes. This
      encapsulating technique allows the production of flexible capsules with an
      emulsion as the capsule core. It is important to mention that the magnetic
      nanoparticles were stable and dispersed throughout the complete process, which is
      an important difference to most magnetic alginate-based materials. In a series of
      experiments, we used spinning drop techniques, capsule squeezing experiments and
      interfacial shear rheology in order to determine the surface Young moduli, the
      surface Poisson ratios and the surface shear moduli of the magnetically sensitive
      alginate capsules. In additional experiments, we analysed the capsule deformation
      in magnetic fields. In spinning drop and capsule squeezing experiments, water
      droplets were pressed out of the capsules at elevated values of the mechanical
      load. This phenomenon might be used for the mechanically triggered release of
      water-soluble ingredients. After drying the emulsion-filled capsules, we produced
      capsules, which only contained a homogeneous oil phase with stable suspended
      magnetic nanoparticles (organic ferrofluid). In the dried state, the thin
      alginate membranes of these particles were rather rigid. These dehydrated
      capsules could be stored at ambient conditions for several months without
      changing their properties. After exposure to water, the alginate membranes
      rehydrated and became flexible and deformable again. During this swelling
      process, water diffused back in the capsule. This long-term stability and
      rehydration offers a great spectrum of different applications as sensors, soft
      actuators, artificial muscles or drug delivery systems.

PMID- 29323660
TI  - Laser Doppler sensing for blood vessel detection with a biologically inspired
      steerable needle.
AB  - Puncturing blood vessels during percutaneous intervention in minimally invasive
      brain surgery can be a life threatening complication. Embedding a forward looking
      sensor in a rigid needle has been proposed to tackle this problem but, when using
      a rigid needle, the procedure needs to be interrupted and the needle extracted if
      a vessel is detected. As an alternative, we propose a novel optical method to
      detect a vessel in front of a steerable needle. The needle itself is based on a
      biomimetic, multi-segment design featuring four hollow working channels.
      Initially, a laser Doppler flowmetry probe is characterized in a tissue phantom
      with optical properties mimicking those of human gray matter. Experiments are
      performed to show that the probe has a 2.1 mm penetration depth and a 1 mm off
      axis detection range for a blood vessel phantom with 5 mm s-1 flow velocity. This
      outcome demonstrates that the probe fulfills the minimum requirements for it to
      be used in conjunction with our needle. A pair of Doppler probes is then embedded
      in two of the four working channels of the needle and vessel reconstruction is
      performed using successive measurements to determine the depth and the off-axis
      position of the vessel from each laser Doppler probe. The off-axis position from
      each Doppler probe is then used to generate a 'detection circle' per probe, and
      vessel orientation is predicted using tangent lines between the two. The vessel
      reconstruction has a depth root mean square error (RMSE) of 0.3 mm and an RMSE of
      15 degrees  in the angular prediction, showing real promise for a future clinical
      application of this detection system.

PMID- 29323661
TI  - Versatile technique for assessing thickness of 2D layered materials by XPS.
AB  - X-ray photoelectron spectroscopy (XPS) has been utilized as a versatile method
      for thickness characterization of various two-dimensional (2D) films. Accurate
      thickness can be measured simultaneously while acquiring XPS data for chemical
      characterization of 2D films having thickness up to approximately 10 nm. For
      validating the developed technique, thicknesses of few-layer graphene (FLG), MoS2
      and amorphous boron nitride (a-BN) layer, produced by microwave plasma chemical
      vapor deposition (MPCVD), plasma enhanced chemical vapor deposition (PECVD), and
      pulsed laser deposition (PLD) respectively, were accurately measured. The
      intensity ratio between photoemission peaks recorded for the films (C 1s, Mo 3d,
      B 1s) and the substrates (Cu 2p, Al 2p, Si 2p) is the primary input parameter for
      thickness calculation, in addition to the atomic densities of the substrate and
      the film, and the corresponding electron attenuation length (EAL). The XPS data
      was used with a proposed model for thickness calculations, which was verified by
      cross-sectional transmission electron microscope (TEM) measurement of thickness
      for all the films. The XPS method determines thickness values averaged over an
      analysis area which is orders of magnitude larger than the typical area in cross
      sectional TEM imaging, hence provides an advanced approach for thickness
      measurement over large areas of 2D materials. The study confirms that the
      versatile XPS method allows rapid and reliable assessment of the 2D material
      thickness and this method can facilitate in tailoring growth conditions for
      producing very thin 2D materials effectively over a large area. Furthermore, the
      XPS measurement for a typical 2D material is non-destructive and does not require
      special sample preparation. Therefore, after XPS analysis, exactly the same
      sample can undergo further processing or utilization.

PMID- 29323662
TI  - CRISPR-Cas9-based genome-wide screening of Toxoplasma gondii.
AB  - Apicomplexan parasites, such as Toxoplasma gondii, cause extensive morbidity and
      mortality in humans and livestock, highlighting the need for a deeper
      understanding of their molecular biology. Although techniques for the generation
      of targeted gene disruptions have long been available for apicomplexans, such
      methods are not readily scalable to the entire genome. We recently used CRISPR
      Cas9 to disrupt all nuclear protein-coding genes in T. gondii using a pooled
      format. The method relies on transfection of a guide RNA library into parasites
      constitutively expressing Cas9. Here, we present the complete workflow of such a
      screen, including preparation of the guide RNA library, growth and testing of the
      recipient strain, generation of the mutant population, culture conditions for the
      screen, preparation of genomic DNA libraries, next-generation sequencing of the
      guide RNA loci, and analysis to detect fitness-conferring genes. This method can
      be deployed to study how culture conditions affect the repertoire of genes needed
      by parasites, which will enable studies of their metabolic needs, host
      specificity, and drug-resistance mechanisms. In addition, by manipulating the
      background in which the screen is performed, researchers will be able to
      investigate genetic interactions, which may help uncover redundancy or epistasis
      in the parasite genome. Using this method, a genome-wide screen and its analysis
      can be completed in 3 weeks, after ~1 month of preparation to generate the
      library and grow the cells needed, making it a powerful tool for uncovering
      functionally important genes in apicomplexan parasites.

PMID- 29323663
TI  - Multiplexed proteome analysis with neutron-encoded stable isotope labeling in
      cells and mice.
AB  - We describe a protocol for multiplexed proteomic analysis using neutron-encoded
      (NeuCode) stable isotope labeling of amino acids in cells (SILAC) or mice
      (SILAM). This method currently enables simultaneous comparison of up to nine
      treatment and control proteomes. Another important advantage over traditional
      SILAC/SILAM is that shorter labeling times are required. Exploiting the small
      mass differences that correspond to subtle differences in the neutron-binding
      energies of different isotopes, the amino acids used in NeuCode SILAC/SILAM
      differ in mass by just a few milliDaltons. Isotopologs of lysine are introduced
      into cells or mammals, via the culture medium or diet, respectively, to
      metabolically label the proteome. Labeling time is ~2 weeks for cultured cells
      and 3-4 weeks for mammals. The proteins are then extracted, relevant samples are
      combined, and these are enzymatically digested with lysyl endopeptidase (Lys-C).
      The resultant peptides are chromatographically separated and then mass analyzed.
      During mass spectrometry (MS) data acquisition, high-resolution MS1 spectra
      (>=240,000 resolving power at m/z = 400) reveal the embedded isotopic signatures,
      enabling relative quantification, while tandem mass spectra, collected at lower
      resolutions, provide peptide identities. Both types of spectra are processed
      using NeuCode-enabled MaxQuant software. In total, the approximate completion
      time for the protocol is 3-5 weeks.

PMID- 29323664
TI  - On-demand synthesis of organozinc halides under continuous flow conditions.
AB  - Organozinc reagents are versatile building blocks for introducing C(sp2)-C(sp3)
      and C(sp3)-C(sp3) bonds into organic structures. However, despite their ample
      synthetic versatility and broad functional group tolerance, the use of organozinc
      reagents in the laboratory is limited because of their instability, exothermicity
      and water sensitivity, as well as their labor-intensive preparation. Herein, we
      describe an on-demand synthesis of these useful reagents under continuous flow
      conditions, overcoming these primary limitations and supporting widespread
      adoption of these reagents in synthetic organic chemistry. To exemplify this
      procedure, a solution of ethyl zincbromoacetate is prepared by flowing ethyl
      bromoacetate through a column containing metallic zinc. The temperature of the
      column is controlled by a heating jacket and a thermocouple in close contact with
      it. Advice on how to perform the procedure using alternative equipment is also
      given to allow a wider access to the methodology. Here we describe the
      preparation of 50 ml of solution, which takes 1 h 40 min, although up to 250-300
      ml can be prepared with the same column setup at a rate of 30 ml per h. The
      procedure provides the reagent as a clean solution with reproducible
      concentration. Organozinc solutions generated in flow can be coupled to a second
      flow reactor to perform a Reformatsky reaction or can be collected over a flask
      containing the required reagents for a batch Negishi reaction.

PMID- 29323666
TI  - The differential diagnosis of a TP53 genetic testing result.

PMID- 29323665
TI  - Arterial tortuosity syndrome: 40 new families and literature review.
AB  - PURPOSE: We delineate the clinical spectrum and describe the histology in
      arterial tortuosity syndrome (ATS), a rare connective tissue disorder
      characterized by tortuosity of the large and medium-sized arteries, caused by
      mutations in SLC2A10. METHODS: We retrospectively characterized 40 novel ATS
      families (50 patients) and reviewed the 52 previously reported patients. We
      performed histology and electron microscopy (EM) on skin and vascular biopsies
      and evaluated TGF-beta signaling with immunohistochemistry for pSMAD2 and CTGF.
      RESULTS: Stenoses, tortuosity, and aneurysm formation are widespread occurrences.
      Severe but rare vascular complications include early and aggressive aortic root
      aneurysms, neonatal intracranial bleeding, ischemic stroke, and gastric
      perforation. Thus far, no reports unequivocally document vascular dissections or
      ruptures. Of note, diaphragmatic hernia and infant respiratory distress syndrome
      (IRDS) are frequently observed. Skin and vascular biopsies show fragmented
      elastic fibers (EF) and increased collagen deposition. EM of skin EF shows a
      fragmented elastin core and a peripheral mantle of microfibrils of random
      directionality. Skin and end-stage diseased vascular tissue do not indicate
      increased TGF-beta signaling. CONCLUSION: Our findings warrant attention for IRDS
      and diaphragmatic hernia, close monitoring of the aortic root early in life, and
      extensive vascular imaging afterwards. EM on skin biopsies shows disease-specific
      abnormalities.

PMID- 29323668
TI  - Professional responsibilities regarding the provision, publication, and
      dissemination of patient phenotypes in the context of clinical genetic and
      genomic testing: points to consider-a statement of the American College of
      Medical Genetics and Genomics (ACMG).
AB  - Disclaimer: This Points to Consider document is designed as an educational
      resource to provide best practices for medical genetic clinicians, laboratories,
      and journals regarding the provision, publication, and dissemination of patient
      phenotypes in the context of genomic testing, clinical genetic practice, and
      research. While the goal of the document is the improvement of patient care, the
      considerations and practices described should not be considered inclusive of all
      proper considerations and practices or exclusive of others that are reasonably
      directed to obtaining the same goal. In determining the value of any practice,
      clinicians, laboratories, and journals should apply their own professional
      standards and judgment to the specific circumstances presented.The content of
      this article is solely the responsibility of the authors and does not necessarily
      represent the official views of the authors' affiliated institutions.

PMID- 29323667
TI  - Making new genetic diagnoses with old data: iterative reanalysis and reporting
      from genome-wide data in 1,133 families with developmental disorders.
AB  - PURPOSE: Given the rapid pace of discovery in rare disease genomics, it is likely
      that improvements in diagnostic yield can be made by systematically reanalyzing
      previously generated genomic sequence data in light of new knowledge. METHODS: We
      tested this hypothesis in the United Kingdom-wide Deciphering Developmental
      Disorders study, where in 2014 we reported a diagnostic yield of 27% through
      whole-exome sequencing of 1,133 children with severe developmental disorders and
      their parents. We reanalyzed existing data using improved variant calling
      methodologies, novel variant detection algorithms, updated variant annotation,
      evidence-based filtering strategies, and newly discovered disease-associated
      genes. RESULTS: We are now able to diagnose an additional 182 individuals, taking
      our overall diagnostic yield to 454/1,133 (40%), and another 43 (4%) have a
      finding of uncertain clinical significance. The majority of these new diagnoses
      are due to novel developmental disorder-associated genes discovered since our
      original publication. CONCLUSION: This study highlights the importance of
      coupling large-scale research with clinical practice, and of discussing the
      possibility of iterative reanalysis and recontact with patients and health
      professionals at an early stage. We estimate that implementing parent-offspring
      whole-exome sequencing as a first-line diagnostic test for developmental
      disorders would diagnose >50% of patients.

PMID- 29323669
TI  - Cost-effectiveness and comparative effectiveness of cancer risk management
      strategies in BRCA1/2 mutation carriers: a systematic review.
AB  - PURPOSE: To review the evidence for the effectiveness and cost-effectiveness of
      cancer risk management interventions for BRCA carriers. METHODS: Comparative
      effectiveness and cost-effectiveness analyses were identified by searching
      scientific and health economic databases. Eligible studies modeled the impact of
      a cancer risk management intervention in BRCA carriers on life expectancy (LE),
      cancer incidence, or quality-adjusted life years (QALYs), with or without costs.
      RESULTS: Twenty-six economic evaluations and eight comparative effectiveness
      analyses were included. Combined risk-reducing salpingo-oophorectomy and
      prophylactic mastectomy resulted in the greatest LE and was cost-effective in
      most analyses. Despite leading to increased LE and QALYs, combined mammography
      and breast magnetic resonance imaging (MRI) was less likely to be cost-effective
      than either mammography or MRI alone, particularly for women over 50 and BRCA2
      carriers. Variation in patient compliance to risk management interventions was
      incorporated in 11/34 studies with the remaining analyses assuming 100%
      adherence. CONCLUSION: Prophylactic surgery and intensive breast screening are
      effective and cost-effective in models of BRCA carrier risk management. Findings
      were based predominantly on assuming perfect adherence to recommendations without
      assessment of the health-care resource use and costs related to engaging patients
      and maximizing compliance, meaning the real-world impact on clinical outcomes and
      resource use remains unclear.

PMID- 29323670
TI  - Response to Wald et al.

PMID- 29323672
TI  - Quantitative Raman microspectroscopy for water permeability parameters at a
      droplet interface bilayer.
AB  - Using confocal Raman microspectroscopy, we derive parameters for bilayer water
      transport across an isolated nanoliter aqueous droplet pair. For a bilayer formed
      with two osmotically imbalanced and adherent nanoliter aqueous droplets in a
      surrounding oil solvent, a droplet interface bilayer (DIB), the water
      permeability coefficient across the lipid bilayer was determined from monitoring
      the Raman scattering from the C[triple bond, length as m-dash]N stretching mode
      of K3Fe(CN)6 as a measure of water uptake into the swelling droplet of a DIB
      pair. We also derive passive diffusional permeability coefficient for D2O
      transport across a droplet bilayer using O-D Raman signal. This method provides a
      significant methodological advance in determining water permeability coefficients
      in a convenient and reliable way.

PMID- 29323673
TI  - Realization of toroidal magnetic moments in heterometallic 3d-4f metallocycles.
AB  - Toroidal arrangements of magnetic moments are realized in heterometallic Ln6Cu6
      (Ln = Tb and Dy) macrocycles thanks to the magnetic coupling between lanthanide
      and 3d metal ions.

PMID- 29323675
TI  - A systematic examination of classical and multi-center bonding in heteroborane
      clusters.
AB  - This paper presents a systematic study of multicenter and classical bonding on a
      broad series of experimentally known heteroboranes covering closo, nido, arachno
      and hypho types of cages with incorporated tetrel, pnictogen or chalcogen
      heterovertices up to the third-row elements. The nature of bonding is studied
      using a novel quantum-chemical tool, the intrinsic atomic/bond orbital (IAO/IBO)
      approach, which provides a direct connection between quantum chemistry and
      chemical concepts. We also discuss how the computed IBO properties are related to
      molecular observables such as interatomic distances, molecular electrostatic
      potential surfaces and dipole moments.

PMID- 29323674
TI  - Can 5-methylcytosine analogues with extended alkyl side chains guide DNA
      methylation?
AB  - 5-Methylcytosine (MeC) is an endogenous modification of DNA that plays a crucial
      role in DNA-protein interactions, chromatin structure, epigenetic regulation, and
      DNA repair. MeC is produced via enzymatic methylation of the C-5 position of
      cytosine by DNA-methyltransferases (DNMT) which use S-adenosylmethionine (SAM) as
      a cofactor. Hemimethylated CG dinucleotides generated as a result of DNA
      replication are specifically recognized and methylated by maintenance DNA
      methyltransferase 1 (DNMT1). The accuracy of DNMT1-mediated methylation is
      essential for preserving tissue-specific DNA methylation and thus gene expression
      patterns. In the present study, we synthesized DNA duplexes containing MeC
      analogues with modified C-5 side chains and examined their ability to guide
      cytosine methylation by the human DNMT1 protein. We found that the ability of 5
      alkylcytosines to direct cytosine methylation decreased with increased alkyl
      chain length and rigidity (methyl > ethyl > propyl ~ vinyl). Molecular modeling
      studies indicated that this loss of activity may be caused by the distorted
      geometry of the DNA-protein complex in the presence of unnatural alkylcytosines.

PMID- 29323671
TI  - Neurobiology of social behavior abnormalities in autism and Williams syndrome.
AB  - Social behavior is a basic behavior mediated by multiple brain regions and neural
      circuits, and is crucial for the survival and development of animals and humans.
      Two neuropsychiatric disorders that have prominent social behavior abnormalities
      are autism spectrum disorders (ASD), which is characterized mainly by
      hyposociability, and Williams syndrome (WS), whose subjects exhibit
      hypersociability. Here we review the unique properties of social behavior in ASD
      and WS, and discuss the major theories in social behavior in the context of these
      disorders. We conclude with a discussion of the research questions needing
      further exploration to enhance our understanding of social behavior
      abnormalities.

PMID- 29323676
TI  - Facile construction of organometallic rotaxane-terminated dendrimers using
      neutral platinum-acetylides as the main scaffold.
AB  - We present the successful construction of a new family of organometallic rotaxane
      terminated dendrimers using neutral platinum-acetylides as the main scaffold. The
      fourth generation dendrimer has 24 rotaxane moieties on the surface termini in a
      monodisperse manner.

PMID- 29323677
TI  - Displacement of carbonates in Ca2UO2(CO3)3 by amidoxime-based ligands from free
      energy simulations.
AB  - Amidoxime-based ligands are effective in uranium extraction by displacing
      carbonates in Ca2UO2(CO3)3, the dominant uranyl species in seawater. However, a
      detailed understanding of the displacement process has been lacking. Here we use
      classical molecular dynamics combined with umbrella sampling to map the complete
      displacement process and the free-energy profiles by the simple acetamidoximate
      (AO-) and the more complex glutardiamidoximate (B2- and HB-) ligands.
      Interestingly, we find that the two Ca2+ ions in Ca2UO2(CO3)3 can greatly
      facilitate the displacement of the first two carbonate groups. Displacing the
      third carbonate is however significantly more uphill than the first two. With the
      help of an additional Ca2+ ion, the third carbonate displacement can be made less
      uphill. Comparing AO- and B2-/HB- ligands, we find that the displacement by the
      latter is thermodynamically more favorable due to the chelate effect. Our free
      energy simulations based on classical molecular dynamics simulations reveal key
      atomistic details and quantify the thermodynamic driving force during the
      carbonate displacement of Ca2UO2(CO3)3 by amidoxime-based ligands. These findings
      will be useful in understanding seawater uranium extraction by amidoxime-grafted
      polymeric sorbents.

PMID- 29323678
TI  - Catalytic nucleophilic 'umpoled' pi-allyl reagents.
AB  - After seminal Tsuji-Trost reactions (palladium catalyzed allylation of
      nucleophiles via pi-allyl intermediates as electrophiles), the idea of reversal
      reactivity of pi-allyl intermediates (i.e. pi-allyl as nucleophiles) has been
      stated since the eighties. Thanks to different transition metal sources and the
      modification of their electronic environment through the use of additives and
      ligands, such 'reactivity switch' of pi-allyl intermediates proved its
      powerfulness allowing high control in regio-, diastereo- and enantio
      selectivities. These methodologies have thus emerged as efficient methods in the
      catalytic enantioselective allylation of carbonyl compounds and imines with a
      deep impact on natural product and/or drug elaboration. This tutorial review
      highlights the concept of 'umpoled' reactivity of pi-allyl intermediates, relying
      on selected recent examples.

PMID- 29323679
TI  - Reaction-based fluorescent probe for the selective and sensitive detection of
      thiophenols with a large Stokes shift and its application in water samples.
AB  - Although widely used in organic synthesis, pharmaceuticals and agrochemicals,
      thiophenol has brought about a series of ecological problems due to its high
      toxicity. Therefore, the development of efficient methods to discriminate
      thiophenols from aliphatic thiols is of great importance. In this work, a new
      reaction-based turn-on red fluorescence probe for the detection of thiophenols
      has been developed for the first time by employing dicyanomethylene-4H-pyran
      (DCM) as a fluorescence reporter and 2,4-dinitrobenzene-sulfonate (DNBS) as a
      recognition unit. The probe displayed a highly selective and sensitive (63 fold
      fluorescence enhancement) response to thiophenols over aliphatic thiols.
      Additionally, the probe also exhibited a large Stokes shift (159 nm) and the
      detection limit reached as low as 8.3 nM. Moreover, this probe was also proved
      suitable for the quantification of thiophenol in real environmental water
      samples.

PMID- 29323680
TI  - Controlling orthogonal self-assembly through cis-trans isomerization of a non
      covalent palladium complex dimer.
AB  - The trans-configured square-planar complex of dichloropalladium and chiral
      monodentate phosphine ligands forms self-complementary dimers through 16 hydrogen
      bonded amides and pi-pi stacking in chlorinated solvents. The self-assembly is
      controlled by cis-trans isomerisation of the metal center, where the trans
      configuration governs the dimer formation.

PMID- 29323681
TI  - The structure of a lanthanide complex at an extractant/water interface studied
      using heterodyne-detected vibrational sum frequency generation.
AB  - Solvent extraction plays an integral part in the separation and purification of
      metals. Because extractants generally used as complexing agents for metal
      extractions, such as di-(2-ethylhexyl)phosphoric acid (HDEHP) for lanthanide
      extractions, are amphiphilic, they come to an organic/water interface, and the
      interface plays a crucial role as the site of the formation of metal complexes
      and the subsequent transfer reaction to an organic phase. Despite the importance
      of the interface for metal solvent extractions, its molecular-level structure is
      unclear because of the experimental difficulties. Here we studied the structure
      of a trivalent europium (Eu3+) complex with HDEHP formed at the HDEHP
      monolayer/water interface using heterodyne-detected vibrational sum frequency
      generation (HD-VSFG) spectroscopy. The study on the HDEHP/water interface enables
      us to investigate the structure of the interfacial Eu3+ complex by excluding the
      migration of Eu3+ into an organic phase after the complex formation at the
      interface. The interface-selective vibrational Imchi(2) spectra observed using HD
      VSFG of the interface of HDEHP/aqueous Eu(NO3)3 solution in the 2800-3500 cm-1
      region indicate that Eu3+ at the HDEHP/water interface is bonded by HDEHP from
      the air side and by water molecules from the water side. To the best of our
      knowledge, such metal complex structures have not been identified in organic or
      water solutions.

PMID- 29323682
TI  - Two polymorphic Co(ii) field-induced single-ion magnets with enormous angular
      distortion from the ideal octahedron.
AB  - A mononuclear complex [Co(neo)(PhCOO)2,], neo = neocuproine, PhCOO- = the
      benzoate anion, was prepared in two polymorph forms crystallizing in the C2/c,
      (1) and P21/c, (2) space groups. The polymorphs differ in the Co-O bond lengths
      and the level of trigonal distortion of their coordination polyhedra. The static
      and dynamic magnetic properties of these compounds were thoroughly studied by
      experimental (magnetometry) and theoretical (ab initio calculations) methods. The
      analysis of magnetic data was performed using the spin Hamiltonian formalism or
      the L-S model considering also the orbital angular momentum. It was revealed that
      both polymorphs possess a very large magnetic anisotropy with a pronounced
      rhombic character leading to the separation of the Kramers doublets larger than
      120 cm-1. The measurements of alternating current susceptibility revealed that
      both polymorphs behave as field induced single molecule magnets with a small
      barrier of spin reversal (U = 22.1 K (for 1) and 17.1 K (for 2)) which indicates
      that relaxation processes other than the thermally activated Orbach process take
      place.

PMID- 29323684
TI  - Maximizing the absorption of small cosolutes inside neutral hydrogels: steric
      exclusion versus hydrophobic adhesion.
AB  - In this work the equilibrium absorption of nanometric cosolutes (which could
      represent drugs, reactants, small globular proteins and other kind of
      biomacromolecules) inside neutral hydrogels is studied. We specially focus on
      exploring, for different swelling states, the competition between the steric
      exclusion induced by the cross-linked polymer network constituting the hydrogel,
      and the solvent-induced short-range hydrophobic attraction between the polymer
      chains and the cosolute particle. For this purpose, the cosolute partition
      coefficient is calculated by means of coarse-grained grand canonical Monte Carlo
      simulations, and the results are compared to theoretical predictions based on the
      calculation of the excluded and binding volume around the polymer chains. For
      small hydrophobic attractions or large cosolute sizes, the steric repulsion
      dominates, and the partition coefficient decreases monotonically with the polymer
      volume fraction, phim. However, for large enough hydrophobic attraction strength,
      the interplay between hydrophobic adhesion and the steric exclusion leads to a
      maximum in the partition coefficient at certain intermediate polymer density.
      Good qualitative and quantitative agreement is achieved between simulation
      results and theoretical predictions in the limit of small phim, pointing out the
      importance of geometrical aspects of the cross-linked polymer network, even for
      hydrogels in the swollen state. In addition, the theory is able to predict
      analytically the onset of the maximum formation in terms of the details of the
      cosolute-monomer pair interaction, in good agreement with simulations too.
      Finally, the effect of the many-body attractions between the cosolute and
      multiple polymer chains is quantified. The results clearly show that these many
      body attractions play a very relevant role determining the cosolute binding,
      enhancing its absorption in more than one order of magnitude.

PMID- 29323685
TI  - Coarsening dynamics of ferromagnetic granular networks-experimental results and
      simulations.
AB  - We investigate the phase separation of a shaken mixture of glass and magnetised
      steel spheres after a sudden quench of the shaker amplitude. After quenching,
      transient networks of steel spheres emerge in the experiment. For the developing
      network clusters we estimate the number of spheres in them, and the
      characteristic path lengths. We find that both quantities follow a log-normal
      distribution function. Moreover, we study the temporal evolution of the networks.
      In the sequence of snapshots we observe an initial regime, where the network
      incubates, followed by a temporal regime where network structures are elongated
      and broken, and finally a regime where the structures have relaxed to compact
      clusters of rounded shapes. This phaenomenology resembles the initial, elastic
      and hydrodynamic regimes observed by H. Tanaka [J. Phys.: Condens. Matter, 2000,
      12, R207] during the viscoelastic phase separation for dynamically asymmetric
      mixtures of polymers. In order to discriminate the three regimes we investigate
      in the experiment order parameters like the mean number of neighbors and the
      efficiency of the networks. In order to capture the origin for a viscoelastic
      phase separation in our granular mixture, we use a simple simulation approach.
      Not aiming at a quantitative description of the experimental results, we rather
      use the simulations to define the key interactions in the experimental system.
      This way, we discover that along with dipolar and steric interactions, there is
      an effective central attraction between the magnetised spheres that is
      responsible for the coarsening dynamics. Our simulations show as well three
      regimes in the evolution of characteristic order parameters.

PMID- 29323686
TI  - Negative Poisson's ratio and high-mobility transport anisotropy in SiC6
      siligraphene.
AB  - The diverse forms of silicon carbides lead to versatile properties, but an
      auxetic allotrope at zero pressure has never been reported. Here, using first
      principles calculations we propose a two-dimensional (2D) auxetic silicon carbide
      material, namely SiC6 siligraphene. The plausibility of the SiC6 siligraphene is
      verified by the low formation energy, positive phonon spectrum and high
      mechanical stability. The unique framework of sp2 carbon and sp3 silicon atoms
      leads to unusual in-plane negative Poisson's ratios and electronic properties
      superior to both graphene and silicene. SiC6 siligraphene possesses a natural
      band gap of 0.73 eV and a high carrier mobility. The theoretical mobility in the
      order of 104 cm2 V-1 s-1 for electrons along the [1[combining macron]10]
      direction is comparable to the hole mobility in black phosphorene, whereas the
      hole transport along the [110] direction is blocked. Both the electronic band
      structure and carrier mobility of the SiC6 siligraphene can be tuned by applying
      external strain. A possible synthetic route is also proposed. The exotic
      properties make SiC6 siligraphene a versatile and promising 2D material for
      applications in nanomechanics and nanoelectronics.

PMID- 29323683
TI  - Ru(ii) polypyridyl complexes as photocages for bioactive compounds containing
      nitriles and aromatic heterocycles.
AB  - Photocaging allows for precise spatiotemporal control over the release of
      biologically active compounds with light. Most photocaged molecules employ
      organic photolabile protecting groups; however, biologically active compounds
      often contain functionalities such as nitriles and aromatic heterocycles that
      cannot be caged with organic groups. Despite their prevalence, only a few studies
      have reported successful caging of nitriles and aromatic heterocycles. Recently,
      Ru(ii)-based photocaging has emerged as a powerful method for the release of
      bioactive molecules containing these functional groups, in many cases providing
      high levels of spatial and temporal control over biological activity. This
      Feature Article discusses recent developments in applying Ru(ii)-based
      photocaging towards biological problems. Our groups designed and synthesized
      Ru(ii)-based platforms for the photoinduced delivery of cysteine protease and
      cytochrome P450 inhibitors in order to achieve selective control over enzyme
      inhibition. We also reported Ru(ii) photocaging groups derived from higher
      denticity ancillary ligands that possess photophysical and photochemical
      properties distinct from more traditional Ru(ii)-based caging groups. In
      addition, for the first time, we are able to rapidly synthesize and screen Ru(ii)
      polypyridyl complexes that elicit desired properties by solid-phase synthesis.
      Finally, our work also defined steric and orbital mixing effects that are
      important factors in controlling photoinduced ligand exchange.

PMID- 29323688
TI  - Preventing HIV Infection-What Pediatricians Should Know About HIV Pre-Exposure
      Prophylaxis.
AB  - I recently diagnosed my first adolescent patient with new-onset HIV. As a primary
      care pediatrician, these cases are rare. I cried with the shock of the initial
      diagnosis, just as the patient did when I told him. One of my first thoughts was
      how could I have served him better. He had been inconsistent with condom use, and
      had several partners. I had encouraged safe sex practices, told him to talk to
      his partners about pregnancy prevention, and screened for sexually transmitted
      disease nearly every time he came into my office. However, there was one more
      thing I could have done that may have spared him this diagnosis in the first
      place. I could have prescribed HIV Pre-Exposure Prophylaxis (PrEP). This article
      is meant to introduce primary care pediatricians to the idea of HIV PrEP. The
      article reviews patient eligibility, how to prescribe HIV PrEP, as well as drug
      monitoring and follow-up. [Pediatr Ann. 2018;47(1):e2-e4.].

PMID- 29323689
TI  - Pediatric Endocrinology.

PMID- 29323690
TI  - Premature Adrenarche.
AB  - Adrenarche is when a child's adrenal cortex starts to secrete adrenal androgen
      precursors. Dehydroepiandrosterone (DHEA) is the most abundant product of the
      adrenal cortex, and is a weak androgen agonist thought to be responsible for the
      clinical signs of pubarche by conversion to more potent androgens, testosterone,
      and dihydrotestosterone. DHEA's extra-adrenal sulfation product,
      dehydroepiandrosterone sulfate, is a stable marker for adrenal androgenic
      activity. Pubarche is the physical manifestation of androgenic hormone
      production, and includes the development of pubic and axillary hair, adult body
      odor, and acne. This stage is usually considered premature if it commences before
      age 8 years in girls or age 9 years in boys. Premature adrenarche is a diagnosis
      of exclusion, as true centrally mediated precocious puberty, congenital adrenal
      hyperplasia, exogenous androgen exposure, and androgen-secreting tumors must be
      ruled out. Premature adrenarche may be associated with a history of an infant who
      was small for gestational age at birth who then gained weight rapidly thereafter
      or became obese. In some instances, premature adrenarche may predict functional
      ovarian hyperandrogenism in adolescence. Management of premature adrenarche is
      largely aimed at observation, lifestyle adjustments for weight concerns, and
      monitoring for future possible persistent androgen excess and insulin resistance.
      [Pediatr Ann. 2018;47(1):e7-e11.].

PMID- 29323691
TI  - Premature Thelarche.
AB  - Premature thelarche is a benign condition that affects young girls and may be
      interpreted as a sign of central precocious puberty (CPP). Parental concern is
      common when breast development is noted in a young girl. It is important to
      differentiate premature thelarche from CPP, as the latter is a more serious
      disorder that may affect final adult height and menarcheal age, and may have
      psychological implications as well. Distinguishing between the two conditions
      clinically may help the patients avoid unnecessary testing. Pediatricians can
      play a pivotal role by providing reassurance to families and helping alleviate
      parental anxiety. This article reviews the clinical presentation of premature
      thelarche, its usual course, and implications. [Pediatr Ann. 2018;47(1):e12
      e15.].

PMID- 29323692
TI  - Delayed Puberty.
AB  - Delayed puberty is defined as the absence of physical signs of puberty 2 to 2.5
      standard deviations above the mean age and affects approximately 2% of
      adolescents. Causes of delayed puberty are broadly divided into two categories:
      hypergonadotropic hypogonadism and hypogonadotropic hypogonadism. One exception
      to this classification system is constitutional delay of growth and puberty, the
      most common cause of delayed puberty. For the general pediatrician, knowledge of
      the different causes and initial steps to evaluation is crucial when a patient
      with delayed puberty presents. [Pediatr Ann. 2018;47(1):e16-e22.].

PMID- 29323693
TI  - Menstrual Irregularities.
AB  - Irregular menstrual cycles are a common complaint among adolescents. There are
      multiple etiologies for menstrual irregularities. It is important to have a
      stepwise approach, including obtaining a thorough medical history and performing
      a physical examination, when patients present. Understanding the characteristics
      of the menstrual cycle helps determine the etiology. This article discusses the
      differential diagnosis of irregular menstrual cycles, as well as the approach to
      evaluation and management. The common conditions and defining characteristics are
      also discussed. [Pediatr Ann. 2018;47(1):e23-e28.].

PMID- 29323694
TI  - The Short Child.
AB  - Growth is one of the most important characteristics of human development. This
      process occurs from the moment of conception through the final stages of puberty.
      There are multiple factors that contribute to growth in humans. Although it may
      seem complex, a pediatrician should note that growth can be fairly predictable.
      The advantage to predictable changes in growth is that clinicians should be able
      to promptly detect any deviation and evaluate it in a timely manner. One of the
      most helpful tools to assess changes in growth is the use of a growth chart. This
      article provides the clinician with the necessary tools to identify growth
      abnormalities, investigate appropriately to arrive at an accurate diagnosis, and
      either treat or, when indicated, provide a timely referral to a pediatric
      endocrinologist. [Pediatr Ann. 2018;47(1):e29-e35.].

PMID- 29323695
TI  - Lead Toxicity in the Pediatric Patient with Sickle Cell Disease: Unique Risks and
      Management.
AB  - Lead toxicity is the result of lead ingestion, one of the most common ingestions
      in the pediatric population. Nationwide and statewide efforts to recognize and
      curtail this epidemic have led to declining rates of toxicity. In patients with
      sickle cell disease (SCD), lead toxicity can be an elusive diagnosis due to
      overlapping symptom profiles, and inconsistent follow-up with a primary care
      physician can make the diagnosis even more difficult. In this article, two
      illustrative cases of lead toxicity in patients with SCD are described. The
      discussion reviews the current risk factors, screening, and inpatient management
      of lead toxicity, as well as describing the unique and sometimes confounding
      presentations of lead toxicity versus sickle cell crisis. [Pediatr Ann.
      2018;47(1):e36-e40.].

PMID- 29323698
TI  - XIST accelerates neuropathic pain progression through regulation of miR-150 and
      ZEB1 in CCI rat models.
AB  - LncRNAs are reported to participate in neuropathic pain development. LncRNA X
      inactive specific transcript (XIST) is involved in the progression of various
      cancers. However, the role of XIST in neuropathic pain remains unclear. In our
      present study, we established a chronic constriction injury (CCI) rat model and
      XIST was found to be greatly upregulated both in the spinal cord tissues and in
      the isolated microglias of CCI rats. Inhibition of XIST inhibited neuropathic
      pain behaviors including mechanical and thermal hyperalgesia. Moreover, decrease
      of XIST repressed neuroinflammation through inhibiting COX-2, tumor necrosis
      factor (TNF)-alpha and IL-6 and in CCI rats. Previously, miR-150 has been
      reported to restrain neuropathic pain by targeting TLR5. Currently, miR-150 was
      predicted to be a microRNA target of XIST, which indicated a negative correlation
      between miR-150 and XIST. miR-150 was remarkably decreased in CCI rats and
      overexpression of miR-150 can significantly suppress neuroinflammation-related
      cytokines. Furthermore, ZEB1 was exhibited to be a direct target of miR-150 and
      we found it was overexpressed in CCI rats. Silencing ZEB1 was able to inhibit
      neuropathic pain in vivo and downreguation of XIST decreased ZEB1, which can be
      reversed by miR-150 inhibitors. Taken these together, we indicated that XIST can
      induce neuropathic pain development in CCI rats via upregulating ZEB1 by acting
      as a sponge of miR-150. It was revealed that XIST/miR-150/ZEB1 axis can be
      provided as a therapeutic target in neuropathic pain.

PMID- 29323697
TI  - Identification of a novel botulinum neurotoxin gene cluster in Enterococcus.
AB  - The deadly neurotoxins of Clostridium botulinum (BoNTs) comprise eight serotypes
      (A-G; X). The neurotoxin gene cluster encoding BoNT and its accessory proteins
      includes an operon containing an ntnh gene upstream of the boNT gene. Another
      operon contains either ha (haemagglutinin) or orfX genes (of unknown function).
      Here we describe a novel boNT gene cluster from Enterococcus sp. 3G1_DIV0629,
      with a typical ntnh gene and an uncommon orfX arrangement. The neurotoxin
      (designated putative eBoNT/J) contains a metallopeptidase zinc-binding site, a
      translocation domain and a target cell attachment domain. Structural properties
      of the latter suggest a novel targeting mechanism with consequent implications
      for application by the pharmaceutical industry. This is the first complete boNT
      gene cluster identified in a non-clostridial genome.

PMID- 29323696
TI  - Regulation of neuronal development and function by ROS.
AB  - Reactive oxygen species (ROS) have long been studied as destructive agents in the
      context of nervous system ageing, disease and degeneration. Their roles as
      signalling molecules under normal physiological conditions is less well
      understood. Recent studies have provided ample evidence of ROS-regulating
      neuronal development and function, from the establishment of neuronal polarity to
      growth cone pathfinding; from the regulation of connectivity and synaptic
      transmission to the tuning of neuronal networks. Appreciation of the varied
      processes that are subject to regulation by ROS might help us understand how
      changes in ROS metabolism and buffering could progressively impact on neuronal
      networks with age and disease.

PMID- 29323699
TI  - Leukotriene B4 receptor 2 regulates the proliferation, migration, and barrier
      integrity of bronchial epithelial cells.
AB  - The airway epithelium plays a crucial role in the pathogenesis of asthma. The
      functions of leukotriene B4 receptor 2 (BLT2) on the airway epithelial cells
      remains unknown. In our study, BLT2 expression in 16HBE bronchial epithelial
      cells were manipulated by transfection with BLT2 overexpression plasmid or BLT2
      small interference RNA. 16HBE cells were then exposed to BLT2 antagonist
      (LY255283) or BLT2 agonist (12(S)-hydroxyheptadeca-5Z,8E,10E-trienoic acid [12
      HHT] or CAY10583). The results showed that BLT2 overexpression, 12-HHT
      stimulation, or CAY10583 treatment resulted in the enhanced proliferation and
      migration of 16HBE cells. In addition, BLT2 showed an inhibitory effect on
      epithelial permeability as illustrated by the measurement of transepithelial
      electrical resistance (TER) and epithelial permeability, and a promoting effect
      on the levels of tight junction proteins (occludin and claudin-4) and
      phosphorylated p38 as demonstrated by real-time PCR and Western blotting
      analyses. These results suggest BLT2 as a key determinant of airway epithelial
      barrier integrity. On the contrary, RNAi-mediated knockdown or LY255283 treatment
      had reversed effects on the proliferation, migration, and epithelial barrier
      integrity. Together, our findings suggest the critical roles of BLT2 on the
      functions of bronchial epithelial cells and that BLT2 agonists are potential
      therapeutic agents for asthma treatment.

PMID- 29323700
TI  - Heat shock protein (Hsp) regulation by muscarinic acetylcholine receptor (mAChR)
      activation in the rat hippocampus.
AB  - The cholinergic system plays a crucial role in modulating in the central nervous
      system physiological responses such as neurogenesis, neuronal differentiation,
      synaptic plasticity, and neuroprotection. In a recent study, we showed that
      Oxotremorine-M, a non-selective muscarinic acetylcholine receptor agonist, is
      able to transactivate the fibroblast growth factor receptor and to produce a
      significant increase in the hippocampal primary neurite outgrowth. In the present
      study we aimed to explore in the rat hippocampus the possible effect of acute or
      chronic treatment with Oxotremorine-M on some heat shock proteins (Hsp60, Hsp70,
      Hsp90) and on activation of related transcription factor heat shock factor 1
      (HSF1). Following single injection of Oxotremorine-M (0.4 mg/kg) all Hsps
      examined were significantly increased in at least one of the time points studied
      (24, 48, and 72 hr). Treatment with Oxotremorine-M significantly increased the
      level of phosphorylated HSF1 in all time points studied, without change of
      protein levels. Similar pattern of Hsps changes was obtained following chronic
      Oxotremorine-M treatment (0.2 mg/kg) for 5 days. Surprisingly, following chronic
      treatment for 10 days no changes were observed in Hsps. The muscarinic
      acetylcholine receptor antagonist scopolamine (1 mg/kg) was able to completely
      block Oxotremorine-M effects on Hsps. In conclusion, considering the function of
      Hsps in protecting neuronal cells from deleterious proteotoxic stress, for
      example, protein mis-folding and aggregation, the results obtained indicate that
      muscarinic acetylcholine receptor activation may have implications in potential
      treatment of neurodegenerative disorders linked to protein aggregation, such as
      Alzheimer disease.

PMID- 29323701
TI  - Positive diversity-functioning relationships in model communities of
      methanotrophic bacteria.
AB  - Biodiversity enhances ecosystem functions such as biomass production and nutrient
      cycling. Although the majority of the terrestrial biodiversity is hidden in
      soils, very little is known about the importance of the diversity of microbial
      communities for soil functioning. Here, we tested effects of biodiversity on the
      functioning of methanotrophs, a specialized group of soil bacteria that plays a
      key role in mediating greenhouse gas emissions from soils. Using pure strains of
      methanotrophic bacteria, we assembled artificial communities of different
      diversity levels, with which we inoculated sterile soil microcosms. To assess the
      functioning of these communities, we measured methane oxidation by gas
      chromatography throughout the experiment and determined changes in community
      composition and community size at several time points by quantitative PCR and
      sequencing. We demonstrate that microbial diversity had a positive overyielding
      effect on methane oxidation, in particular at the beginning of the experiment.
      This higher assimilation of CH4 at high diversity translated into increased
      growth and significantly larger communities towards the end of the study. The
      overyielding of mixtures with respect to CH4 consumption and community size were
      positively correlated. The temporal CH4 consumption profiles of strain
      monocultures differed, raising the possibility that temporal complementarity of
      component strains drove the observed community-level strain richness effects;
      however, the community niche metric we derived from the temporal activity
      profiles did not explain the observed strain richness effect. The strain richness
      effect also was unrelated to both the phylogenetic and functional trait diversity
      of mixed communities. Overall, our results suggest that positive biodiversity
      ecosystem-function relationships show similar patterns across different scales
      and may be widespread in nature. Additionally, biodiversity is probably also
      important in natural methanotrophic communities for the ecosystem function
      methane oxidation. Therefore, maintaining soil conditions that support a high
      diversity of methanotrophs may help to reduce the emission of the greenhouse gas
      methane.

PMID- 29323703
TI  - Integrative omics analysis of p53-dependent regulation of metabolism.
AB  - Accumulated evidence in the last decade implies that regulation of metabolism by
      p53 represents a reviving mechanism vital to prevent tumorigenesis. To gain a
      more in-depth understanding of metabolic regulation by baseline levels of p53, we
      employed both metabolomics and transcriptomics analysis with human colon cancer
      cell-line HCT116 depleted of p53. Metabolomics analyses with UPLC/quadrupole time
      of-flight mass spectrometry identified 283 significantly changed metabolites
      including 138 important metabolites. Transcriptomics analysis with microarray
      revealed 1317 differentially expressed genes. By integrated analysis of both
      omics data, we found nucleotides metabolism and sulfur-related metabolism are of
      great importance. Our study provided a pilot comprehensive view of the metabolism
      regulated by p53 and suggests several potential p53 targets in metabolism for
      further study.

PMID- 29323702
TI  - Sirtuin 3 silencing improves oxaliplatin efficacy through acetylation of MnSOD in
      colon cancer.
AB  - Sirtuin 3 (SIRT3) is the major mitochondria deacetylase and regulates ROS levels
      by targeting several key proteins, such as those involved in mitochondrial
      function and antioxidant defenses. This way, SIRT3 balances ROS production and
      scavenging and promotes cell survival. The aim of this study was to analyze the
      effect of SIRT3 silencing on the antioxidant response in SW620 colon cancer cell
      line, and whether this intervention could improve efficacy of oxaliplatin, a
      common drug used to treat colon cancer. For this purpose, we obtained stable
      clones of SW620 with SIRT3 knockdown and determined parameters such as ROS levels
      and ROS production, levels of several antioxidant enzymes, cell viability, and
      apoptosis. Results showed that after SIRT3 silencing, both ROS levels and
      production were increased, and antioxidant enzymes gene expression was
      significantly reduced. Furthermore, manganese superoxide dismutase levels and
      enzymatic activity were reduced. Combination of SIRT3 knockdown with oxaliplatin
      treatment further increased ROS production and apoptosis, reducing cell
      viability. Finally, survival curves on colon cancer patients suggested that SIRT3
      expression is related to a poorer prognosis. In conclusion, SIRT3 could be a
      target for colon cancer, since it regulates the antioxidant response and its
      knockdown improves the efficacy of oxaliplatin treatment.

PMID- 29323704
TI  - Reply to The Reply to the letter on the cost-effectiveness of human
      papillomavirus in Punjab further distorts the scientific record.

PMID- 29323705
TI  - The protective effects of distal ischemic treatment on apoptosis and
      mitochondrial permeability in the hippocampus after cardiopulmonary
      resuscitation.
AB  - Apoptosis and mitochondrial dysfunction are the main cause of neurological injury
      after cardiopulmonary resuscitation (CPR). However, the effects of distal
      ischemic treatments on ischemia induced apoptosis are rarely studied, and the
      mechanism by which mitochondrial dysfunction contributes to CPR still unclear. A
      rat model of distal ischemia was established by clipping the right femoral
      artery. Rats were divided into blank, model, pre distal ischemic treatment, per
      treatment, and post-treatment groups. Neurological deficit score was scored to
      evaluate neurologic function after cardiopulmonary resuscitation for 72 hr. We
      employed TUNEL and flow cytometry to measure the rate of apoptosis of hippocampal
      neurons, the integrity of mitochondrial membrane and the degree of mitochondrial
      permeability transition pore (mPTP) opening. The rate of apoptosis rate of
      hippocampal CA1 neurons in the pre-treatment and post-treatment groups were
      significantly lower than that of the model group. Moreover, the integrity of the
      mitochondrial membrane in the pre-treatment and post-treatment groups was higher
      than that in the model and per- treatment groups. Furthermore, the degree of mPTP
      opening was lower in the pre-treatment and post-treatment groups than the
      untreated and per-treatment groups. Taken together, our results show that
      ischemic preconditioning and post processing can maintain the integrity of
      mitochondria, perhaps by inhibiting the opening of mPTP, and reducing apoptosis
      of hippocampal neurons by regulating expression of apoptosis related proteins
      after CPR, to improve neurological function. This study highlights a novel target
      pathway for treatment of CPR.

PMID- 29323706
TI  - The origins and homeostasis of monocytes and tissue-resident macrophages in
      physiological situation.
AB  - Monocytes and macrophages are critical effectors and regulators of innate immune
      response. They not only play crucial and distinctive roles in homeostasis, but
      also contribute to some pathologic processes. The heterogeneity of the macrophage
      lineage has been widely recognized and, in part, is a result of the
      specialization of resident macrophages in particular tissue microenvironments.
      Monocytes are usually known to originate in the bone marrow from a common myeloid
      progenitor that is shared with neutrophils, and they are then released into the
      peripheral blood. However, the origin of tissue-resident macrophages, crucial for
      homeostasis and immunity, has remained controversial until recently. During
      embryonic organogenesis, macrophages derived from yolk sac and fetal liver
      precursors are seeded throughout tissues, persisting in the adulthood as
      resident, self-maintaining populations. After birth, bone marrow-derived
      monocytes can replenish tissue resident macrophages following injury, infection
      and inflammation. In this review, we will mainly summarize our current
      understanding on the origin, ontogeny and fates of tissue macrophages and will
      briefly discuss the molecular regulation of resident macrophage homeostasis in
      physiological situation.

PMID- 29323707
TI  - Ox-LDL induces endothelial cell apoptosis and macrophage migration by regulating
      caveolin-1 phosphorylation.
AB  - Oxidative low-density lipoprotein (ox-LDL) is a risk factor for atherosclerosis.
      Ox-LDL leads to endothelial injury in the initial stage of atherosclerosis. In
      this study, we investigated the role of ox-LDL in endothelial injury and
      macrophage recruitment. We demonstrated that ox-LDL promoted a dose-dependent
      phosphorylation of caveolin-1 in human umbilical vein endothelial cells.
      Phosphorylated caveolin-1 increased ox-LDL uptake. Intracellular accumulation of
      ox-LDL induced NF-kappaB p65 phosphorylation, promoted HMGB1 translocation from
      nucleus to cytoplasm and cytochrome C release from mitochondria to cytoplasm, and
      activated caspase 3, resulting in cell apoptosis. NF-kappaB activation also
      facilitated cavolin-1 phosphorylation and HMGB1 expression. In addition, caveolin
      1 phosphorylation favored HMGB1 release and nuclear translocation of EGR1.
      Nuclear translocation of EGR1 contributed to cytoplasmic translocation of HMGB1.
      The extracellular HMGB1 induced the migration of PMBC-derived macrophages toward
      HUVECs in a TLR4-dependent manner. Our results suggested that ox-LDL promoted
      HUVECs apoptosis and macrophage recruitment by regulating caveolin-1
      phosphorylation.

PMID- 29323708
TI  - MicroRNA501-5p induces p53 proteasome degradation through the activation of the
      mTOR/MDM2 pathway in ADPKD cells.
AB  - Cell proliferation and apoptosis are typical hallmarks of autosomal dominant
      polycystic kidney disease (ADPKD) and cause the development of kidney cysts that
      lead to end-stage renal disease (ESRD). Many factors, impaired by polycystin
      complex loss of function, may promote these biological processes, including cAMP,
      mTOR, and EGFR signaling pathways. In addition, microRNAs (miRs) may also
      regulate the ADPKD related signaling network and their dysregulation contributes
      to disease progression. However, the role of miRs in ADPKD pathogenesis has not
      been fully understood, but also the function of p53 is quite obscure, especially
      its regulatory contribution on cell proliferation and apoptosis. Here, we
      describe for the first time that miR501-5p, upregulated in ADPKD cells and
      tissues, induces the activation of mTOR kinase by PTEN and TSC1 gene repression.
      The increased activity of mTOR kinase enhances the expression of E3 ubiquitin
      ligase MDM2 that in turn promotes p53 ubiquitination, leading to its degradation
      by proteasome machinery in a network involving p70S6K. Moreover, the
      overexpression of miR501-5p stimulates cell proliferation in kidney cells by the
      inhibition of p53 function in a mechanism driven by mTOR signaling. In fact, the
      downregulation of this miR as well as the pharmacological treatment with
      proteasome and mTOR inhibitors in ADPKD cells reduces cell growth by the
      activation of apoptosis. Consequently, the stimulation of cell death in ADPKD
      cells may occur through the inhibition of mTOR/MDM2 signaling and the restoring
      of p53 function. The data presented here confirm that the impaired mTOR signaling
      plays an important role in ADPKD.

PMID- 29323709
TI  - Osteosarcoma-derived extracellular vesicles induce a tumor-like phenotype in
      normal recipient cells.
AB  - Osteosarcoma is the most common primary bone cancer and the most frequent cause
      of bone cancer-related deaths in children and adolescents. Osteosarcoma cells are
      able to establish a crosstalk with resident bone cells leading to the formation
      of a deleterious vicious cycle. We hypothesized that osteosarcoma cells can
      release, in the bone microenvironment, transforming Extracellular Vesicles (EVs)
      involved in regulating bone cell proliferation and differentiation, thereby
      promoting tumor growth. We assessed EV production by three osteosarcoma cell
      lines with increasing aggressiveness in order to investigate their roles in the
      communication between osteosarcoma cells and normal recipient cells. Osteosarcoma
      derived EVs were used to treat the murine fibroblast cell line NIH3T3 and to
      study the induction of tumor-like phenotypes. Our results showed that
      osteosarcoma cell lines are able to produce EVs that fuse to recipient cells,
      with a very high uptake efficiency. The treatment of recipient NIH3T3 with
      osteosarcoma-derived EVs induced substantial biological and functional effects,
      as an enhanced proliferation and survival capability under starved conditions,
      high levels of activated survival pathways, an increased migration, adhesion, and
      3D sphere formation and the acquired capability to grow in an anchorage
      independent manner. Moreover, in murine NIH3T3 we found human mRNAs of TNF-alpha,
      IL-6, and TGF-beta, as well as a de novo expression of murine MMP-9 and TNF-alpha
      following the treatment of human osteosarcoma-derived EVs.

PMID- 29323710
TI  - Blocking PI3K/AKT signaling inhibits bone sclerosis in subchondral bone and
      attenuates post-traumatic osteoarthritis.
AB  - PI3K/AKT signaling is essential in regulating pathophysiology of osteoarthritis
      (OA). However, its potential modulatory role in early OA progression has not been
      investigated yet. Here, a mouse destabilization OA model in the tibia was used to
      investigate roles of PI3K/AKT signaling in the early subchondral bone changes and
      OA pathological process. We revealed a significant increase in PI3K/AKT signaling
      activation which was associated with aberrant bone formation in tibial
      subchondral bone following destabilizing the medial meniscus (DMM), which was
      effectively prevented by treatment with PI3K/AKT signaling inhibitor LY294002.
      PI3K/AKT signaling inhibition attenuated articular cartilage degeneration. Serum
      and bone biochemical analyses revealed increased levels of MMP-13, which was
      found expressed mainly by osteoblastic cells in subchondral bone. However, this
      MMP-13 induction was attenuated by LY294002 treatment. Furthermore, PI3K/AKT
      signaling was found to enhance preosteoblast proliferation, differentiation, and
      expression of MMP-13 by activating NF-kappaB pathway. In conclusion, inhibition
      of PI3K/AKT/NF-kappaB axis was able to prevent aberrant bone formation and
      attenuate cartilage degeneration in OA mice.

PMID- 29323711
TI  - HIV-1 increases extracellular amyloid-beta levels through neprilysin regulation
      in primary cultures of human astrocytes.
AB  - Since the success of combined antiretroviral therapy, HIV-1-infected individuals
      are now living much longer. This increased life expectancy is accompanied by a
      higher prevalence of HIV-1 associated neurocognitive disorders. Rising too is the
      incidence in these patients of pathological hallmarks of Alzheimer's disease such
      as increased deposition of amyloid beta protein (Abeta). Although neurons are
      major sources of Abeta in the brain, astrocytes are the most numerous glial
      cells, therefore, even a small level of astrocytic Abeta metabolism could make a
      significant contribution to brain pathology. Neprilysin (NEP) is a
      decisive/crucial regulator of Abeta levels. We evaluated the effects of HIV-1 on
      Abeta deposition and the expression and activity of NEP in primary human
      astrocytes. Specifically, no differences in intracellular amyloid deposits were
      found between infected and control cells. However, primary cultures of infected
      astrocytes showed more extracellular Abeta levels compared to controls. This was
      accompanied by reduced expression of NEP and to a significant decrease on its
      activity. These results indicate that the presence of HIV-1 in the brain could
      contribute to the increase of the total burden of cerebral Abeta. This article is
      protected by copyright. All rights reserved.

PMID- 29323712
TI  - Paradoxical side effects of bisphosphonates on the skeleton: What do we know and
      what can we do?
AB  - Bisphosphonates are considered the most effective drugs for controlling adult and
      pediatric osteolytic diseases. Although they have been used successfully for many
      years, several side effects, such as osteonecrosis of the jaw, delayed dental
      eruption, atypical femoral fracture, and alterations to the bone growth system,
      have been described. After an overview of nitrogenous bisphosphonate, the purpose
      of this article is to describe their mechanisms of action and current
      applications, review the preclinical and clinical evidence of their side effects
      in the skeleton ("what we know"), and describe current recommendations for
      preventing and managing these effects ("what we can do"). Finally, promising
      future directions on how to limit the occurrence of these side effects will be
      presented.

PMID- 29323713
TI  - NEAT1 contributes to breast cancer progression through modulating miR-448 and
      ZEB1.
AB  - Breast cancer is a kind of common female cancers. Increasing evidence has
      exhibited that lncRNAs exert a crucial role in breast cancer. So far, the
      mechanism of lncRNAs in breast cancer is still not well established. In our
      current study, we focused on the biological role of lncRNA Nuclear Enriched
      Abundant Transcript 1 (NEAT1) in breast cancer. We observed that NEAT1 levels
      were significantly increased in human breast cancer cells including MCF-7, MDA-MB
      453, MDA-MB-231, and SKBR3 cells compared to normal mammary epithelial cells MCF
      10A while miR-448 was decreased. We found that downregulation of NEAT1 was able
      to inhibit the growth of breast cancer cells and miR-448 mimic exerted the
      similar function. Bioinformatics analysis and dual luciferase reporter assays
      confirmed the negative correlation between NEAT1 and miR-448 in vitro. In
      addition, ZEB1 was predicted as a novel mRNA target of miR-448. Overexpression of
      NEAT1 can induce breast cancer cell growth, migration, and invasion by inhibiting
      miR-448 and upregulating ZEB1. It was demonstrated that NEAT1 can increase ZEB1
      levels while miR-448 mimic can repress ZEB1. It was speculated in our study that
      NEAT1 can serve as a competing endogenous lncRNA (ceRNA) to modulate ZEB1 by
      sponging miR-448 in breast cancer. To conclude, we uncovered that NEAT1
      participated in breast cancer progression by regulating miR-448 and ZEB1. NEAT1
      can be provided as a vital biomarker in breast cancer diagnosis and treatment
      therapy.

PMID- 29323714
TI  - A new gold standard approach to characterize the transport of Si across cell
      membranes in animals.
AB  - Silicon (Si) is increasingly recognized as an essential trace element in animals,
      especially since the identification of mammalian Si transport systems and Si
      responsive genes not long ago. During many years, however, efforts to gain
      substantial insight into the biological role of this element in animals have
      achieved partial success due in part to the unavailability of validated protocols
      to study Si movement across biological membranes. To circumvent such limitations,
      we have developed a general transport assay in which cellular Si content was
      determined by automated electrothermal atomic absorption spectrophotometry. We
      have found this assay to provide great analytic sensitivity with Si detection
      thresholds of less than 1 uM, that is, below or very close to the concentration
      range of animal cells. We have also found this assay to provide valid and cost
      effective determinations in Si transport studies while requiring workable
      quantities of samples. The protocol described here should thus become gold
      standard toward accelerated progress in the field of Si transport.

PMID- 29323715
TI  - Alleviation of palmitic acid-induced endoplasmic reticulum stress by augmenter of
      liver regeneration through IP3R-controlled Ca2+ release.
AB  - The aberrant release of Ca2+ from the endoplasmic reticulum (ER) contributes to
      the onset of ER stress, which is closely related to the pathogenesis of non
      alcoholic fatty liver disease. We previously reported that augmenter of liver
      regeneration (ALR) alleviates ER stress and protects hepatocytes from
      lipotoxicity. However, the link between ALR protection and the suppression of ER
      stress remains unclear. In this study, we investigated whether the protection
      against liver steatosis afforded by ALR is related to its inhibition of calcium
      overflow from the ER to the mitochondria. The treatment of HepG2 cells with
      palmitic acid (PA) upregulated IP3R expression, triggering ER-luminal Ca2+
      release and inducing ER stress. However, in ALR-transfected (ALR-Tx) HepG2 cells,
      PA-induced cell injury was clearly alleviated compared with that in vector-Tx
      cells. After exposure to PA, IP3R expression was downregulated and ER stress was
      effectively inhibited in the ALR-Tx cells, and ER-Ca2+ release and simultaneous
      mitochondrial Ca2+ uptake were lower than those in vector-Tx cells. The knockdown
      of ALR expression with shRNA abolished the protective effects afforded by ALR
      transfection. PA treatment also suppressed the interaction between BCL-2 and IP3R
      in HepG2 cells, whereas this interaction was massively enhanced in the ALR-Tx
      cells, effectively reducing the IP3R-mediated ER-Ca2+ release and thus
      mitochondrial Ca2+ influx. Our results suggest that the inhibition of ER stress
      by ALR is related to the interruption of the interaction between BCL2 and IP3R,
      demonstrating a novel mechanism of ER stress resistance in ALR-Tx cells.

PMID- 29323716
TI  - Oxidative burden in familial hypercholesterolemia.
AB  - Familial hypercholesterolemia (FH) is a genetic disorder characterized by high
      serum levels of low-density lipoprotein cholesterol (LDL-c). FH is characterized
      by accelerated development of atherosclerosis and represents the most frequent
      hereditary cause of premature coronary heart disease. Mutations of the LDL
      receptor gene are the genetic signature of FH, resulting in abnormal levels of
      circulating LDLs. Moreover, FH promotes the generation of reactive oxygen species
      (ROS) which is another key mechanism involved in atherosclerosis development and
      progression. The aim of this narrative review is to update the current knowledge
      on the pathophysiological mechanisms linking FH to ROS generation and their
      detrimental impact on atherosclerotic pathophysiology. With this purpose, we
      reviewed experimental and clinical data on the association between FH and OS and
      the functional role of OS as a promoter of inflammation and atherosclerosis. In
      this regard, oxidant species such as oxidized LDL, malondialdehyde, ROS, and
      isoprostanes emerged as leading mediators of the oxidative injury in FH. In
      conclusion, targeting oxidative stress may be a promising therapeutic strategy to
      reduce atherogenesis in patients with FH.

PMID- 29323717
TI  - Chondrogenic differentiation of human scalp adipose-derived stem cells in
      Polycaprolactone scaffold and using Freeze Thaw Freeze method.
AB  - Human adipose tissue has been identified as a viable alternative source for
      mesenchymal stem cells. SADSCs were isolated from human scalp biopsy and then
      were characterized by Flow cytometry. SADSCS expressed CD90, CD44, and CD105 but
      did not express CD45 surface marker. Growth factors were used for chondrogenesis
      induction. Histology and immunohistology methods and gene expression by real-time
      PCR 14 days after induced cells have shown the feature of chondrocytes in their
      morphology and extracellular matrix in both inducing patterns of combination and
      cycling induction. Moreover, the expression of gene markers of chondrogenesis for
      example collagen type II aggrecan and SOX9 has shown by real-time PCR assay.
      Then, SADSCs were seeded alone on polycaprolatone (PCL) and with Freeze thaw
      Freeze (PCL+FTF) scaffolds and SADSCs differentiated toward the chondrogenic
      lineage and chondrogenesis induction were evaluated using scanning electron
      microcopy (SEM) and MTT assay. Our results showed that SADSCs were also similar
      to the other adipose-derived stem cells. Using TGF-beta3 and BMP-6 were effective
      for chondrogenesis induction. Therefore using of TGF-beta3 and BMP-6 growth
      factors may be the important key for in vitro chondrogenesis induction. The bio
      composite of PCL+FTF nanofibrous scaffolds enhance the chondroblast
      differentiation and proliferation compared to PCL scaffolds .Therefore, our model
      will make it possible to study the mechanism of transition from chondroblast to
      chondrocyte.

PMID- 29323718
TI  - Effect of miR-182 on hepatic fibrosis induced by Schistosomiasis japonica by
      targeting FOXO1 through PI3K/AKT signaling pathway.
AB  - The study aimed to investigate the impact of miR-182 and FOXO1 on S. japonica
      induced hepatic fibrosis. Microarray analysis was performed to screen out
      differential expressed miRNAs and mRNAs. Rat hepatic fibrosis model and human
      hepatocellular cell line LX-2 were used to study the effect of miR-182 and FOXO1.
      qRT-PCR and Western blot were used to detect the expression of miR-182, FOXO1 or
      other fibrosis markers. The targeting relationship between FOXO1 and miR-182 was
      verified by luciferase reporter assay. Immunohistochemistry or immunofluorescence
      staining was conducted to detect FOXO1 or alpha-SMA in rat hepatic tissues. Cell
      viability and apoptosis were detected by MTT assay and flow cytometry. The
      expression of PI3K/AKT pathway-related proteins was detected by Western blot. miR
      182 was highly expressed in liver fibrosis samples, and FOXO1 expression was
      negatively correlated with miR-182 expression. After transfection of miR-182,
      FOXO1 expression was down-regulated, with the results of LX-2 cells proliferation
      inhibition and apoptosis induction, as well as the aggravation of rat hepatic
      fibrosis. The expression of p-AKT/AKT and p-S6/S6 was increased, meaning that the
      PI3K/AKT signal pathway was activated. The results were reversed when treated
      with Wortmannin (PI3K inhibitor). After transfection of miR-182 inhibitor, FOXO1
      expression was up-regulated, LX-2 cell proliferation was inhibited, and apoptosis
      rate was increased. High-expressed miR-182 and low-expressed FOXO1 promoted
      proliferation and inhibiting apoptosis on liver fibrosis cells, stimulating the
      development of S. japonica-induced hepatic fibrosis through feeding back to
      PI3K/AKT signaling pathway.

PMID- 29323719
TI  - The multifaceted link between inflammation and human diseases.
AB  - Increasing reports on epidemiological, diagnostic, and clinical studies suggest
      that dysfunction of the inflammatory reaction results in chronic illnesses such
      as cancer, arthritis, arteriosclerosis, neurological disorders, liver diseases,
      and renal disorders. Chronic inflammation might progress if injurious agent
      persists; however, more typically than not, the response is chronic from the
      start. Distinct to most changes in acute inflammation, chronic inflammation is
      characterized by the infiltration of damaged tissue by mononuclear cells like
      macrophages, lymphocytes, and plasma cells, in addition to tissue destruction and
      attempts to repair. Phagocytes are the key players in the chronic inflammatory
      response. However, the important drawback is the activation of pathological
      phagocytes, which might result from continued tissue damage and lead to harmful
      diseases. The longer the inflammation persists, the greater the chance for the
      establishment of human diseases. The aim of this review was to focus on advances
      in the understanding of chronic inflammation and to summarize the impact and
      involvement of inflammatory agents in certain human diseases.

PMID- 29323720
TI  - Tfcp2l1 safeguards the maintenance of human embryonic stem cell self-renewal.
AB  - Tfcp2l1 is a transcription factor critical for mouse embryonic stem cell (mESC)
      maintenance. However, its role in human ESCs (hESCs) remains unclear. Here, we
      investigated the role of Tfcp2l1 in controlling hESC activity and showed that
      Tfcp2l1 is functionally important in the maintenance of hESC identity. Tfcp2l1
      expression is highly enriched in hESCs and dramatically decreases upon
      differentiation. Forced expression of Tfcp2l1 promoted hESC self-renewal.
      Functional analysis of the mutant forms of Tfcp2l1 revealed that both the CP2-
      and SAM-like domains are indispensable for Tfcp2l1 to maintain the
      undifferentiated state of hESCs. Notably, the CP2-like domain is closely related
      to the suppression of definitive endoderm and mesoderm commitment. Accordingly,
      knockdown of Tfcp2l1 significantly induced differentiation preferentially into
      definitive endoderm and mesoderm. Further studies found that inhibition of
      Wnt/beta-catenin signaling pathway by IWR1 is able to eliminate the
      differentiation caused by Tfcp2l1 downregulation. Taken together, these findings
      reveal the unique and crucial role of Tfcp2l1 in the determination of hESC fate
      and will expand our understanding of the self-renewal and differentiation
      circuitry in hESCs.

PMID- 29323721
TI  - Brain-derived neurotrophic factor modulates cholesterol homeostasis and
      Apolipoprotein E synthesis in human cell models of astrocytes and neurons.
AB  - In the central nervous system, cholesterol is critical to maintain membrane
      plasticity, cellular function, and synaptic integrity. In recent years, much
      attention was focused on the role of cholesterol in brain since a breakdown of
      cholesterol metabolism has been associated with different diseases. Brain-derived
      neurotrophic factor (BDNF) was previously reported to elicit cholesterol
      biosynthesis and promote the accumulation of presynaptic proteins in cholesterol
      rich lipid rafts, but no data are available on its ability to modulate
      physiological mechanisms involved in cholesterol homeostasis. Major aim of this
      research was to investigate whether BDNF influences cholesterol homeostasis,
      focusing on the effect of the neurotrophin on Apolipoprotein E (ApoE) synthesis,
      cholesterol efflux from astrocytes and cholesterol incorporation into neurons.
      Our results show that BDNF significantly stimulates cholesterol efflux by
      astrocytes, as well as ATP binding cassette A1 (ABCA1) transporter and ApoE
      expression. Conversely, cholesterol uptake in neurons was downregulated by BDNF.
      This effect was associated with the increase of Liver X Receptor (LXR)-beta
      expression in neuron exposed to BDNF. The level of apoptosis markers, that is,
      cleaved caspase 3 and poly ADP ribose polymerase (PARP), was found increased in
      neurons treated with high cholesterol, but significantly lower when the cells
      were exposed to cholesterol in the presence of BDNF, thus suggesting a
      neuroprotective role of the neurotrophin, likely through its reducing effect of
      neuronal cholesterol uptake. Interestingly, cholesterol stimulates BDNF
      production by neurons. Overall, our findings evidenced a novel role of BDNF in
      the modulation of ApoE and cholesterol homeostasis in glial and neuronal cells.

PMID- 29323722
TI  - Exosomal miRNAs as novel cancer biomarkers: Challenges and opportunities.
AB  - A biomarker with high specificity and sensitivity, is a basic requirement for non
      invasive cancer diagnosis. Exosomes are a type of lipid bilayer extracellular
      vesicles (EVs), containing different components, including proteins, lipids, DNA,
      messenger RNA (mRNA), and non-coding RNAs. Increasing evidence indicates that
      nucleic acids are protected by exosome lipid membrane. These vesicles are almost
      released from all cell types, into biological fluids. In cancer, the expression
      of microRNAs (miRNAs), located in the tumor cell-derived exosomes, is deregulated
      and it could be led to metastasis and therapy resistance. Due to the presence of
      exosomes in various body fluids and the stability of miRNAs in exosomes, exosomal
      miRNAs can provide a new class of biomarkers for early and minimally invasive
      cancer diagnosis. In this article, we review the miRNAs and their roles in
      cancer. Furthermore, we explain the different types of EVs, especially exosomes,
      and their functional roles in cancer. At the end, we discuss about the importance
      of exosomal miRNAs for cancer diagnosis. As well as, we briefly summarize the
      exosome isolation techniques and obstacles, limiting the clinical applications of
      exosomal miRNAs.

PMID- 29323724
TI  - Autoregulation of RANK ligand in oral squamous cell carcinoma tumor cells.
AB  - Oral squamous cell carcinoma (OSCC) is the most common malignancy among oral
      cancers and shows potent activity for local bone invasion. Receptor activator of
      nuclear factor kappaB (RANK) ligand (RANKL) is critical for bone-resorbing
      osteoclast formation. We previously demonstrated that OSCC tumor cells express
      high levels of RANKL. In this study, confocal microscopy demonstrated RANKL
      specific receptor, RANK expression in OSCC tumor cell lines (SCC1, SCC12, and
      SCC14a). We also confirmed the expression of RANK and RANKL in primary human OSCC
      tumor specimens. However, regulatory mechanisms of RANKL expression and a
      functional role in OSCC tumor progression are unclear. Interestingly, we
      identified that RANKL expression is autoregulated in OSCC tumor cells. The RANKL
      specific inhibitor osteoprotegerin (OPG) treatment to OSCC cells inhibits
      autoregulation of RANKL expression. Further, we showed conditioned media from
      RANKL CRISPR-Cas9 knockout OSCC cells significantly decreased osteoclast
      formation and bone resorption activity. In addition, RANKL increases OSCC tumor
      cell proliferation. RANKL treatment to OSCC cells demonstrated a dose-dependent
      increase in RANK intracellular adaptor protein, TRAF6 expression, and activation
      of IKK and IkappaB signaling molecules. We further identified that transcription
      factor NFATc2 mediates autoregulation of RANKL expression in OSCC cells. Thus,
      our results implicate RANKL autoregulation as a novel mechanism that facilitates
      OSCC tumor cell growth and osteoclast differentiation/bone destruction.

PMID- 29323723
TI  - Haplo-insufficiency of Bcl2-associated athanogene 3 in mice results in
      progressive left ventricular dysfunction, beta-adrenergic insensitivity, and
      increased apoptosis.
AB  - Bcl2-associated athanogene 3 (BAG3) is a 575 amino acid protein that is found
      predominantly in the heart, skeletal muscle, and many cancers. Deletions and
      truncations in BAG3 that result in haplo-insufficiency have been associated with
      the development of dilated cardiomyopathy. To study the cellular and molecular
      events attributable to BAG3 haplo-insufficiency we generated a mouse in which one
      allele of BAG3 was flanked by loxP recombination sites (BAG3fl/+ ). Mice were
      crossed with alpha-MHC-Cre mice in order to generate mice with cardiac-specific
      haplo-insufficiency (cBAG3+/-) and underwent bi-weekly echocardiography to assess
      their cardiac phenotype. By 10 weeks of age, cBAG3+/- mice demonstrated increased
      heart size and diminished left ventricular ejection fraction when compared with
      non-transgenic littermates (Cre-/- BAG3fl/+ ). Contractility in adult myocytes
      isolated from cBAG3+/- mice were similar to those isolated from control mice at
      baseline, but showed a significantly decreased response to adrenergic
      stimulation. Intracellular calcium ([Ca2+ ]i ) transient amplitudes in myocytes
      isolated from cBAG3+/- mice were also similar to myocytes isolated from control
      mice at baseline but were significantly lower than myocytes from control mice in
      their response to isoproterenol. BAG3 haplo-insufficiency was also associated
      with decreased autophagy flux and increased apoptosis. Taken together, these
      results suggest that mice in which BAG3 has been deleted from a single allele
      provide a model that mirrors the biology seen in patients with heart failure and
      BAG3 haplo-insufficiency.

PMID- 29323725
TI  - Serum IgG antibodies from healthy subjects up to 100 years old react to JC
      polyomavirus.
AB  - JC polyomavirus (JCPyV) was identified in 1971 in the brain tissue of a patient
      (J.C.) affected by the progressive multifocal leukoencephalopathy (PML). JCPyV
      encodes for the oncoproteins large T antigen (Tag) and small t-antigen (tag).
      These oncoproteins are responsible of the cell transformation and tumorigenesis
      in experimental animals. JCPyV is ubiquitous in human populations. After the
      primary infection, which is usually asymptomatic, JCPyV remains lifelong in the
      host in a latent phase. Its reactivation may occur in heathy subjects and
      immunocompromised patients. Upon reactivation, JCPyV could reach (i) the CNS
      inducing the PML, (ii) the kidney of transplant patients causing the organ
      rejection. Association between JCPyV, which is a small DNA tumor virus, and
      gliomas and colorectal carcinomas has been published. In the present
      investigation, we report on a new indirect ELISA with two specific synthetic
      peptides mimicking JCPyV VP1 immunogenic epitopes to detect specific serum IgG
      antibodies against JCPyV. Serum samples of healthy subjects (n = 355) ranging 2
      100 years old, were analyzed by this new indirect ELISA. The linear peptides VP1
      K and VP1 N resemble the natural JCPyV VP1 capsidic epitopes constituting a
      docking site for serum antibodies. Data from this innovative immunologic assay
      indicate that the overall prevalence of JCPyV-VP1 antibodies in healthy subjects
      is at 39%. The innovative indirect ELISA with JCPyV VP1 mimotopes seems to be a
      useful method to detect specific IgG antibodies against this virus, without cross
      reactivity with the closely related SV40 and BKPyV polyomaviruses.

PMID- 29323726
TI  - Computational chemical biology and drug design: Facilitating protein structure,
      function, and modulation studies.
AB  - Over the past quarter of a century, there has been rapid development in
      structural biology, which now can provide solid evidence for understanding the
      functions of proteins. Concurrently, computational approaches with particular
      relevance to the chemical biology and drug design (CBDD) field have also
      incrementally and steadily improved. Today, these methods help elucidate detailed
      working mechanisms and accelerate the discovery of new chemical modulators of
      proteins. In recent years, integrating computational simulations and predictions
      with experimental validation has allowed for more effective explorations of the
      structure, function and modulation of important therapeutic targets. In this
      review, we summarize the main advancements in computational methodology
      development, which are then illustrated by several successful applications in
      CBDD. Finally, we conclude with a discussion of the current major challenges and
      future directions in the field.

PMID- 29323727
TI  - Alternative diagnostic criteria for idiopathic hypersomnia: A 32-hour protocol.
AB  - OBJECTIVE: To assess the diagnostic value of extended sleep duration on a
      controlled 32-hour bed rest protocol in idiopathic hypersomnia (IH). METHODS: One
      hundred sixteen patients with high suspicion of IH (37 clear-cut IH according to
      multiple sleep latency test criteria and 79 probable IH), 32 with hypersomnolence
      associated with a comorbid disorder (non-IH), and 21 controls underwent
      polysomnography, modified sleep latency tests, and a 32-hour bed rest protocol.
      Receiver operating characteristic curves were used to find optimal total sleep
      time (TST) cutoff values on various periods that discriminate patients from
      controls. RESULTS: TST was longer in patients with clear-cut IH than other groups
      (probable IH, non-IH, and controls) and in patients with probable IH than non-IH
      and controls. The TST cutoff best discriminating clear-cut IH and controls was 19
      hours for the 32-hour recording (sensitivity = 91.9%, specificity = 85.7%) and 12
      hours (100%, 85.7%) for the first 24 hours. The 19-hour cutoff displayed a
      specificity and sensitivity of 91.9% and 81.2% between IH and non-IH patients.
      Patients with IH above the 19-hour cutoff were overweight, had more sleep
      inertia, and had higher TST on all periods compared to patients below 19 hours,
      whereas no differences were found for the 12-hour cutoff. An inverse correlation
      was found between the mean sleep latency and TST during 32-hour recording in IH
      patients. INTERPRETATION: In standardized and controlled stringent conditions,
      the optimal cutoff best discriminating patients from controls was 19 hours over
      32 hours, allowing a clear-cut phenotypical characterization of major interest
      for research purposes. Sleepier patients on the multiple sleep latency test were
      also the more severe in terms of extended sleep. Ann Neurol 2018;83:235-247.

PMID- 29323728
TI  - Three-dimensional reconstruction of prostate cancer architecture with serial
      immunohistochemical sections: hallmarks of tumour growth, tumour
      compartmentalisation, and implications for grading and heterogeneity.
AB  - AIMS: Conventional morphology of prostate cancer considers only the two
      dimensional (2D) architecture of the tumour. Our aim was to examine the
      feasibility of three-dimensional (3D) reconstruction of tumour morphology based
      on multiple consecutive histological sections and to decipher relevant features
      of prostate cancer architecture. METHODS AND RESULTS: Seventy-five consecutive
      histological sections (5 MUm) of a typical prostate adenocarcinoma (Gleason score
      of 3 + 4 = 7) were immunostained (pan-cytokeratin) and scanned for further 3D
      reconstructions with fiji/imagej software. The main findings related to the
      prostate cancer architecture in this case were: (i) continuity of all glands,
      with the tumour being an integrated system, even in Gleason pattern 4 with poorly
      formed glands-no short-range migration of cells by Gleason pattern 4 (poorly
      formed glands); (ii) no repeated interconnections between the glands, with a
      tumour building a tree-like branched structure with very 'plastic' branches
      (maximal depth of investigation 375 MUm); (iii) very stark compartmentalisation
      of the tumour related to extensive branching, the coexistence of independent
      terminal units of such branches in one 2D slice explaining intratumoral
      heterogeneity; (iv) evidence of a craniocaudal growth direction in interglandular
      regions of the prostate and for a lateromedial growth direction in subcapsular
      posterolateral regions; and (v) a 3D architecture-based description of Gleason
      pattern 4 with poorly formed glands, and its continuum with Gleason pattern 3.
      CONCLUSIONS: Consecutive histological sections provide high-quality material for
      3D reconstructions of the tumour architecture, with excellent resolution. The
      reconstruction of multiple regions in this typical case of a Gleason score 3 + 4
      = 7 tumour provides insights into relevant aspects of tumour growth, the
      continuity of Gleason patterns 3 and 4, and tumour heterogeneity.

PMID- 29323729
TI  - Measurement of two-photon-absorption spectra through nonlinear fluorescence
      produced by a line-shaped excitation beam.
AB  - We propose an innovative experimental approach to estimate the two-photon
      absorption (TPA) spectrum of a fluorescent material. Our method develops the
      standard indirect fluorescence-based method for the TPA measurement by employing
      a line-shaped excitation beam, generating a line-shaped fluorescence emission.
      Such a configuration, which requires a relatively high amount of optical power,
      permits to have a greatly increased fluorescence signal, thus avoiding the photon
      counterdetection devices usually used in these measurements, and allowing to
      employ detectors such as charge-coupled device (CCD) cameras. The method is
      finally tested on a fluorescent isothiocyanate sample, whose TPA spectrum, which
      is measured with the proposed technique, is compared with the TPA spectra
      reported in the literature, confirming the validity of our experimental approach.

PMID- 29323730
TI  - Biochemical and molecular study on interleukin-1beta gene expression and relation
      of single nucleotide polymorphism in promoter region with Type 2 diabetes
      mellitus.
AB  - : Interleukin-1beta (IL-1beta) assumes a centric role in the regulation of immune
      and inflammatory responses and thus has been recognized in immune mediated
      diseases like type 2 diabetes mellitus (T2DM). We aimed to investigate expressed
      level of IL-1beta and its relation with IL-1beta -511T>C polymorphism in T2DM
      patients. This study enrolled 80 subjects (50 patients with T2DM and 30 healthy
      control subjects). Laboratory investigations included fasting (FBG) and 2 h
      postprandial blood sugar (2 h PBG), HBA1c, lipid profile, and renal function
      tests. Genotyping of IL-1beta -511T>C (rs16944) SNP assay by real-time PCR and
      relative quantitation of IL-1beta gene expression transcript by real-time PCR.
      RESULTS: T2DM patients had significantly higher FBG and 2 h PBG, HBA1c, LDLc, TC,
      TG, systolic, and diastolic BP while lower HDLc compared with control group. IL 1
      beta -511 T>C, CC genotype and C allele were significantly associated with risk
      of T2DM with odds ratio (OR) 4.73, 95%CI (1.21-18.39) and OR 2.27, 95%CI (1.72
      4.40), respectively. Moreover, diabetic patients had significantly higher IL 1-
      beta gene transcript compared with control group (P < 0.001). CC genotype of IL 1
      beta -511 T > C had the highest significant level of IL 1- beta gene transcript
      demonstrated compared with C/T and T/T genotypes (P < 0.001) in patients.
      CONCLUSION: C allele of IL-1 beta -511 T >C could be considered risk factor
      contributor to T2DM and excess level of IL-1 beta transcript may disclose to some
      degree the inflammatory role of cytokines in T2DM.

PMID- 29323731
TI  - Expression of PD-L1 correlates with pleomorphic morphology and histological
      patterns of non-small-cell lung carcinomas.
AB  - AIMS: As immunomodulatory therapy is being integrated into treatment regimens for
      non-small-cell lung carcinoma, we aimed to prospectively collect data on the
      immunohistochemical profile of tumours assessed in our institution and to
      correlate this with morphological tumour features. METHODS AND RESULTS:
      Immunohistochemistry for programmed death-ligand 1 (PD-L1) was considered to be
      adequate when >100 tumour cells were seen microscopically. When adequate, PD-L1
      staining was scored as <1%, >=1-49% or >=50% positive membrane staining within
      tumour cells only. There were 197 assessable cases, of which 87% of those with
      pleomorphic features (n = 39) showed >=50% positivity for PD-L1 expression, as
      compared with only 33% of cases without pleomorphic features (P < 0.05) (90%
      versus 25% in resected cases). Further correlation of PD-L1 expression with
      architectural patterns within the tumours was performed in 74 adenocarcinoma
      resections. All invasive mucinous adenocarcinomas scored <1%. All lepidic
      components in non-mucinous adenocarcinoma resections scored <1%. Thirty-five per
      cent of the acinar/papillary components and 53% of the solid/micropapillary
      components were positive for PD-L1 expression. CONCLUSIONS: There are significant
      differences in PD-L1 expression in relation to histological patterns, with
      particularly high levels in those with pleomorphic features and low/undetectable
      levels in invasive mucinous adenocarcinomas and the lepidic components of non
      mucinous adenocarcinomas. Assessment of PD-L1 expression in a resected
      adenocarcinoma with a lepidic component may therefore not be reliable when
      immumodulatory therapy for recurrent disease is being considered, and either re
      biopsy or limiting assessment to the invasive component may be more appropriate.

PMID- 29323732
TI  - Analogous on-axis interference topographic phase microscopy (AOITPM).
AB  - The refractive index (RI) of a sample as an endogenous contrast agent plays an
      important role in transparent live cell imaging. In tomographic phase microscopy
      (TPM), 3D quantitative RI maps can be reconstructed based on the measured
      projections of the RI in multiple directions. The resolution of the RI maps not
      only depends on the numerical aperture of the employed objective lens, but also
      is determined by the accuracy of the quantitative phase of the sample measured at
      multiple scanning illumination angles. This paper reports an analogous on-axis
      interference TPM, where the interference angle between the sample and reference
      beams is kept constant for projections in multiple directions to improve the
      accuracy of the phase maps and the resolution of RI tomograms. The system has
      been validated with both silica beads and red blood cells. Compared with
      conventional TPM, the proposed system acquires quantitative RI maps with higher
      resolution (420 nm @lambda = 633 nm) and signal-to-noise ratio that can be
      beneficial for live cell imaging in biomedical applications.

PMID- 29323733
TI  - Photo-induced toxicity following exposure to crude oil and ultraviolet radiation
      in 2 Australian fishes.
AB  - Some polycyclic aromatic hydrocarbons (PAHs), components of crude oil, are known
      to cause increased toxicity when organisms are co-exposed with ultraviolet
      radiation, resulting in photo-induced toxicity. The photodynamic characteristics
      of some PAHs are of particular concern to places like Australia with high
      ultraviolet radiation levels. The objective of the present study was to
      characterize the photo-induced toxicity of an Australian North West Shelf oil to
      early life stage yellowtail kingfish (Seriola lalandi) and black bream
      (Acanthopagrus butcheri). The fish were exposed to high-energy water accommodated
      fractions for 24 to 36 h. During the exposure, the fish were either co-exposed to
      full-intensity or filtered natural sunlight and then transferred to clean water.
      At 48 h, survival, cardiac effects, and spinal deformities were assessed.
      Yellowtail kingfish embryos co-exposed to oil and full-spectrum sunlight
      exhibited decreased hatching success and a higher incidence of cardiac
      arrhythmias, compared with filtered sunlight. A significant increase in the
      incidence of pericardial edema occurred in black bream embryos co-exposed to full
      spectrum sunlight. These results highlight the need for more studies
      investigating the effects of PAHs and photo-induced toxicity under environmental
      conditions relevant to Australia. Environ Toxicol Chem 2018;37:1359-1366. (c)
      2018 SETAC.

PMID- 29323734
TI  - Inhibitory effect of circulating fibrocytes on injury repair in acute lung
      injury/acute respiratory distress syndrome mice model.
AB  - The study was aimed to explore the functions of circulating fibrocytes (CFs) on
      injury repair in acute lung injury/acute respiratory distress syndrome (ALI/ARDS)
      mice model and its clinical value as a biomarker for ALI/ARDS. ALI/ARDS mice
      model was established by intratracheal instillation of lipopolysaccharide (LPS).
      Mononuclear cells were isolated from peripheral blood of ALI/ARDS model and flow
      cytometry was used to measure CFs defined as cells positive for CD45 and collagen
      1. Histological changes of lung tissues were evaluated by H&E staining and
      Masson's trichrome staining. The correlations of CFs counts with damnification of
      lung tissue and the severity of pulmonary fibrosis were evaluated by Pearson
      correlation analyses. Western blot was used to detect the protein expression of
      collagen-1. ELISA was applied to determine cytokine CXCL12 concentration.
      Clinical relevance between CFs and ALI/ARDS was investigated. The greater number
      of CFs in the ALI/ARDS group implied higher degree of lung injury and more severe
      pulmonary fibrosis. The protein expression of collagen-1 and concentration of
      cytokine CXCL12 in ALI/ARDS group were higher than that in control group.
      Clinical and prognostic analysis revealed the higher injury degree and death
      rates in ALI/ARDS group than those in control group, and identified a greater
      severity and mortality for patients with ARDS than those with ALI. ROC curve
      analysis indicated the counts of CFs greater than 5.85% can predict death rates
      with AUC = 0.928. CFs had an inhibitory effect on injury repair in ALI/ARDS mice
      model. This might be unfavorable as a clinical marker for progression of
      ALI/ARDS.

PMID- 29323735
TI  - The basis of behavioral momentum in the nonlinearity of strength.
AB  - The persistence of operant responding in the context of distractors and opposing
      forces is of central importance to the success of behavioral interventions. It
      has been successfully analyzed with Behavioral Momentum Theory. Key data from the
      research inspired by that theory are reanalyzed in terms of more molecular
      behavioral mechanisms: the demotivational effects of disruptors, and their
      differential impacts on the target response and other responses that interact
      with them. Behavioral momentum is regrounded as a nonlinear effect of motivation
      and reinforcement rate on response probability and persistence. When response
      probabilities are high, more energy is required to further increase or to
      decrease them than when they are low. Classic Behavioral Momentum Theory effects
      are reproduced with this account. Finally, it is shown how the new account
      involving motivation and competition is closely related to the metaphor of force
      and action that is at the core of Behavioral Momentum Theory.

PMID- 29323736
TI  - MAPK and NF-kappaB signalling pathways regulate the expression of miRNA, let-7f
      in human endocervical epithelial cells.
AB  - MicroRNAs (miRNAs) mediate post-transcriptional gene suppression and are a
      critical component of the complex regulatory networks in epithelial immune
      responses. Transcription of miRNA genes in epithelial cells can be elaborately
      controlled through Toll-like receptors (TLRs), and associated nuclear factor
      kappa-light-chain-enhancer of activated B cells (NF-kappaB) and mitogen-activated
      protein kinase (MAPK) pathways, leading to nuclear transcription factor
      associated-transactivation and transrepression of miRNAs. MiRNA, let-7f is
      involved in the regulation of innate immune responses post TLR3 stimulation in
      human endocervical cells (End1/E6E7) and decreased let-7f is associated with poor
      immune activation. Thus, expression of let-7f is under strict control. However,
      the mechanism by which let-7f is regulated in these cells is not known.
      Therefore, in the present study, we have investigated the role of MAPK and NF
      kappaB in the transcription of let-7f. We report that signalling of TLR3, results
      in activation of multiple signalling pathways including MAPK/ERK, JNK, p38, and
      NF-kappaB. Of these MAPK/ p38 and JNK directly influence the expression of let-7f
      in End1/E6E7 cells. Inhibition of ERK and NF-kappaB up regulates the expression
      of let-7f and its transcription factor, C/EBPbeta. In conclusion, we have
      identified a system through which TLR3 mediated immune response is regulated by
      C/EBPbeta and let-7f through the temporal activation of MAPK and NF-kappaB in
      human endocervical cells.

PMID- 29323737
TI  - MiR-15b/HOTAIR/p53 form a regulatory loop that affects the growth of glioma
      cells.
AB  - Among the malignant tumors of the human central nervous system, gliomas have the
      highest incidence and recurrence rate. Therefore, exploration of the molecular
      mechanism that underlies the development and progression of gliomas is of great
      clinical significance. Many studies have demonstrated that long non-coding RNAs
      (lncRNAs) and microRNAs (miRNAs) play important roles in the development and
      progression of tumors. In the present study, both an RNAhybrid analysis and a
      dual-luciferase reporter gene assay confirmed that microRNA-15b (miR-15b) binding
      sites were present in the sequence of HOX transcript antisense RNA (HOTAIR). The
      present study further demonstrated that miR-15b, HOTAIR, and p53 formed a
      mutually regulated loop. MiR-15b upregulated the expression of p53 but inhibited
      the expression of HOTAIR. In addition, miR-15b was able to regulate the
      expression of HOTAIR through p53. P53 promoted miR-15b expression but inhibited
      HOTAIR expression. Furthermore, the examination of cell proliferation, apoptosis,
      and invasion revealed that both miR-15b and p53 inhibited the proliferation and
      invasion, but promoted the apoptosis, of glioma cells. In contrast, HOTAIR
      exerted effects that were the opposite of those exerted by miR-15b and p53 on
      glioma cells. The upregulation of HOTAIR suppressed the inhibitory effects of miR
      15b and p53 on cell proliferation and invasion as well as the promoting effect of
      miR-15b and p53 on apoptosis. Therefore, it can be concluded that miR-15b,
      HOTAIR, and p53 constitute a regulatory loop that is capable of regulating the
      growth of glioma cells. This finding provides a new target for the treatment of
      gliomas.

PMID- 29323738
TI  - An epididymis-specific secretory protein Clpsl2 critically regulates sperm
      motility, acrosomal integrity, and male fertility.
AB  - The epididymis performs an important role in the maturation of spermatozoa
      including their acquisition of progressive motility and fertilizing ability.
      However, the molecular mechanisms that govern these maturational events are still
      poorly defined. Here we report that Clpsl2, a novel colipase homology, is
      exclusively expressed in the caupt epididymis and conserved in mammalian. Clpsl2
      was secreted into the lumen and covered the acrosome region and principal piece
      of spermatozoa tail. And during epididymal transit, the binding rate between
      Clpsl2 protein and the spermatozoa gradually decreased. Though Clpsl2 had the
      highest identifies with pancreatic colipase (Clps), Clpsl2 lacked those conserved
      amino acids in pancreatic Clps that interacting with lipase, correspondingly, the
      recombinant Clpsl2 protein did not possess the Clps function such as promoting
      the hydrolysis of lipase to its substrate glycerine trioleate. However, sequence
      analysis showed that Clpsl2 has the potency to bind with lipid. Knockdown
      expression of Clpsl2 by lentivirus-mediated RNAi in vivo caused an attenuation of
      spermatozoa motility, a suppressed acrosomal reaction, a decrease of cauda
      spermatozoa number, and subfertility. This study identified a novel and conserved
      molecule, Clpsl2, was specifically expressed in epididymis and involved in the
      regulation of spermatozoa motility, acrosomal integrity, and male fertility.

PMID- 29323739
TI  - Fasudil alleviates pressure overload-induced heart failure by activating Nrf2
      mediated antioxidant responses.
AB  - The RhoA/Rho-kinase cascade plays an important role in many aspects of
      cardiovascular function. This study aims to investigate the protective effects of
      fasudil, a Rho-kinase inhibitor, on pressure overload induced heart failure in
      rats. Pressure overload induced heart failure was induced in SD rats by banding
      the abdominal aorta for 8 weeks. The rats were divided into four groups: Sham,
      TAC, TAC plus low dose of fasudil, and TAC plus high dose of fasudil group. Low
      dose and high dose fasudil were 5 and 10 mg/kg/day, respectively. Rats in the
      Sham and TAC groups were treated with vehicle. Fasudil effectively inhibited TAC
      induced heart failure, as evaluated by echocardiography and transmission electron
      microscopy. Fasudil could significantly promote superoxide dismutase (SOD),
      catalase (CAT), and glutathione peroxidase (GPx) activity and significantly
      decrease malondialdehyde (MDA) content in a dose-dependent maner in TAC rats.
      Consistently, fasudil evoked significant nuclear translocation of Nuclear factor
      (erythroid-derived 2)-like 2 (Nrf2) with increased DNA/promoter binding and
      transactivation of Nrf2 targets. In addition, fasudil increased the content of
      iron as well as transferrin receptor 1 (TfR1) in TAC rats. A mild oxidative
      stress induced by iron may activate the antioxidant enzymes by feedback response.
      Taken together, these results indicate that the protective effect of fasudil may
      be due to its strong antioxidative activities which related with the activated
      Nrf2 and its down-regulated genes. These findings provide a new treatment concept
      and support the benefit of fasudil treatment in heart failure.

PMID- 29323740
TI  - Long non-coding RNA ASBEL promotes osteosarcoma cell proliferation, migration,
      and invasion by regulating microRNA-21.
AB  - Osteosarcoma is the most common malignant bone tumor in children and adolescents
      with high rate of incidence, high frequency of recurrence, and high degree of
      metastasis. This study aimed to investigate the effects of long noncoding RNA
      antisense ncRNA in the abundant in neuroepithelium area (ANA)/B-cell
      translocation gene 3 (BTG3) locus (lncRNA ASBEL) on the pathogenesis of
      osteosarcoma. The expression levels of ASBEL in human osteoblast cells and human
      osteosarcoma cells were evaluated using qRT-PCR. Effects of ASBEL knockdown on
      cell viability, migration, and invasion were detected using trypan blue exclusion
      assay, cell migration, and cell invasion assay, respectively. The regulatory
      effects of ASBEL on microRNA-21 (miR-21) were analyzed using qRT-PCR. The roles
      of miR-21 and protein phosphatase 2A (PP2A), the possible downstream factor of
      miR-21, in osteosarcoma cell proliferation, migration, and invasion were also
      explored. The results showed that ASBEL was highly expressed in osteosarcoma
      cells. Knockdown of ASBEL inhibited osteosarcoma cell viability, migration, and
      invasion, as well as the expression level of miR-21. PP2A was a direct target of
      miR-21, which participated in the effects of ASBEL and miR-21 on the activation
      of phosphatidylinositol 3-kinase/protein kinase 3/glycogen synthase kinase-3beta
      (PI3K/AKT/GSK3beta) and mitogen-activated protein kinase/extracellular regulated
      protein kinase (MEK/ERK) signaling pathways as well as the enhancement of
      osteosarcoma cell proliferation, migration, and invasion. In conclusion, we
      verified that ASBEL-miR-21-PP2A pathway might play critical regulatory effects on
      the pathogenesis of osteosarcoma and could be as the potential therapeutic target
      and biomarker for osteosarcoma treatment.

PMID- 29323741
TI  - Stainless steel wear debris of a scoliotic growth guidance system has little
      local and systemic effect in an animal model.
AB  - Options to treat early-onset scoliosis include guided-growth systems with sliding
      action between rods and pedicle screws. The wear was previously measured in an in
      vitro test, and in this in vivo rabbit model, we evaluated the local and systemic
      biological response to the stainless steel debris. Compared to the previous
      study, a relatively higher volume of representative wear particles with a median
      particle size of 0.84 MUm were generated. Bolus dosages were injected into the
      epidural space at L4-L5 for a minimum of 36 rabbits across three treatment groups
      (negative control, 1.5 mg, and 4.0 mg) and two timepoints (12 and 24 weeks).
      Gross pathology evaluated distant organs and the injection site with a dorsal
      laminectomy to examine the epidural space and dosing site. Peri-implanted
      particle tissues were stained for immunohistochemical and quantitatively analyzed
      for IL-6 and TNF-alpha cytokines. Based on ISO 10993-6:2007 scoring, particles in
      the high-dose group were primarily non-irritant (12 weeks) with one slightly
      irritant. At 24 weeks, inflammatory cell infiltration was non-existent to minimal
      with all groups considered non-irritant at the injection site. Material
      characterization confirmed that particles detected in distant organs were
      stainless steel or contaminants. At 12 weeks, stainless steel groups demonstrated
      statistically increased amounts of cytokine levels compared to control but there
      was a statistical decrease for both at 24 weeks. These findings indicate that
      stainless steel wear debris, comparable to the expected usage from a simulated
      growth guidance system, had no discernible untoward biological effects locally
      and systemically in an animal model. (c) 2018 Orthopaedic Research Society.
      Published by Wiley Periodicals, Inc. J Orthop Res 36:1980-1990, 2018.

PMID- 29323742
TI  - A molecular dynamics investigation into the mechanisms of alectinib resistance of
      three ALK mutants.
AB  - Alectinib, a highly selective next-genetation anaplastic lymphoma kinase (ALK)
      inhibitor, has demonstrated promising antitumor activity in patients with ALK
      positive non-small cell lung carcinomas (NSCLC). However, the therapeutic
      benefits of alectinib is inescapably hampered by the development of acquired
      resistant mutations in ALK. Despite the availability of ample experimental
      mutagenesis data, the molecular origin and the structural motifs under alectinib
      binding affinity deficiencies are still ambiguous. Here, molecular dynamics (MD)
      simulations and molecular mechanics generalized born surface area (MM-GBSA)
      calculation approaches were employed to elucidate the mechanisms of alectinib
      resistance induced by the mutations I1171N, V1180L, and L1198F. The MD results
      reveal that the studied mutations could trigger the dislocation of alectinib as
      well as conformational changes at the inhibitor binding site, thus induce the
      interactional changes between alectinib and mutants. The most influenced regions
      are the ligand binding entrance and the hinge region, which are considered to be
      the dominant binding motifs accounting for the binding affinity loss in mutants.
      The "key and lock mechanism" between the ethyl group at position 9 of alectinib
      and a recognition cavity in the hinge region of ALK is presented to illustrate
      the major molecular origin of drug resistance. Our results provide mechanistic
      insight into the effect of ALK mutations resistant to alectinib, which could
      contribute to further rational design of inhibitors to combat the acquired
      resistance.

PMID- 29323743
TI  - Differential expression profile of long non-coding RNAs in human thoracic aortic
      aneurysm.
AB  - Thoracic aortic aneurysm (TAA) is progressive fatal aortic pathological dilation,
      which is characterized by increased proteoglycans and loss of elastic fibers.
      Recent advances in long non-coding RNAs (lncRNAs), an important regulator in many
      biological processes, suggested the close correlation between expression patterns
      and disease progression. In the present study, the ascending aortic tissues were
      collected from ascending TAA patients (n = 33) and organ donors (n = 16).
      Microarray analysis and real-time PCR were then applied to detect the lncRNA
      expression profiles. A total of 147 differentially expressed lncRNAs were
      determined, including 104 upregulated and 43 downregulated lncRNAs.
      Bioinformatics analysis showed 51.7% of differentially expressed lncRNAs were
      sense-overlapping, and most of the down-regulated lncRNAs were located on
      chromosome 1, 7, and 12. Subgroup analysis of TAA patients indicated that the
      expression of lnc-HLTF-5 was significantly higher in hypertension group than non
      hypertension group (P < 0.05). Spearman correlation analysis further confirmed
      that the lnc-HLTF-5 level was positively correlated with the expanded ascending
      aortic diameter (rs  = 0.483, P = 0.004) and MMP9 level (rs  = 0.465, P = 0.006).
      Our results expanded the lncRNA expression patterns in aortic disease, and
      provided experimental basis for future investigation on TAA pathogenesis.

PMID- 29323744
TI  - MicroRNA-193b-3p regulates matrix metalloproteinase 19 expression in interleukin
      1beta-induced human chondrocytes.
AB  - Micro(mi)RNAs are small, non-coding RNA molecules known to play a significant
      role in osteoarthritis (OA) initiation and development, and similar to matrix
      metalloproteinases (MMPs), they participate in cartilage degeneration and cleave
      multiple extracellular matrices. The aim of this study was to determine whether
      the expression of MMP-19 in interleukin (IL)-1beta-induced human chondrocytes is
      directly regulated by miR-193b-3p. Expression levels of miR-193b-3p and MMP-19 in
      normal and osteoarthritis (OA) human cartilage, and interleukin-1 beta (IL-1beta)
      induced human chondrocytes were determined by real-time polymerase chain
      reaction. Additionally, expression level of MMP-19 in IL-1beta-induced human
      chondrocytes was estimated by Western blotting and immunohistochemistry analyses.
      The effect of miR-193b-3p on MMP-19 expression was evaluated using transient
      transfection of normal human chondrocytes with miR-193b-3p mimic or its antisense
      inhibitor (miR-193b-3p inhibitor), and siMMP-19. The putative binding site of miR
      193b-3p in the 3'-untranslated region (UTR) of MMP-19 mRNA was validated by
      luciferase reporter assay. miR-193b-3p expression was reduced in OA cartilage
      compared to that in normal chondrocytes, while the opposite was observed for MMP
      19. Upregulation of MMP-19 expression was correlated with downregulation of miR
      193b-3p in IL-1beta-stimulated normal chondrocytes. Increase in miR-193b-3p
      levels was associated with silencing of MMP-19. Overexpression of miR-193b-3p
      suppressed the activity of the reporter construct containing the 3'-UTR of human
      MMP-19 mRNA and inhibited the IL-1beta-induced expression of MMP-19 and iNOS in
      chondrocytes, while treatment with miR-193b-3p inhibitor enhanced MMP-19
      expression. MiR-193b-3p is an important regulator of MMP-19 in human chondrocytes
      and may relieve the inflammatory response in OA.

PMID- 29323745
TI  - The dancing thrombus: 4D transesophageal echocardiography in the diagnosis of a
      pedunculated left atrial appendage thrombus.
AB  - It is rare that a left atrial appendage thrombus will grow to the extent that it
      can prolapse into the left ventricle. We report the case of a large prolapsing
      left atrial thrombus diagnosed by 3D echocardiography in a patient presenting
      with a transient ischemic attack.

PMID- 29323746
TI  - Acetabular and spino-pelvic morphologies are different in subjects with
      symptomatic cam femoro-acetabular impingement.
AB  - Acetabular and spino-pelvic (SP) morphological parameters are important
      determinants of hip joint dynamics. This prospective study aimed to determine
      whether acetabular and SP morphological differences exist between hips with and
      without cam morphology and between symptomatic and asymptomatic hips with cam
      morphology. A cohort of 67 patients/hips was studied. Hips were either
      asymptomatic with no cam (Controls, n = 18), symptomatic with cam (n = 26) or
      asymptomatic with cam (n = 23). CT-based quantitative assessments of femoral,
      acetabular, pelvic, and spino-pelvic parameters were performed. Measurements were
      compared between controls and those with a cam deformity, as well as between the
      three groups. Morphological parameters that were independent predictors of a
      symptomatic cam were determined using a regression analysis. Hips with cam
      deformity had slightly smaller subtended angles superior-anteriorly (87 degrees 
      vs. 84 degrees , p = 0.04) and greater pelvic incidence (53 degrees  vs. 48
      degrees , p = 0.003) compared to controls. Symptomatic cams had greater
      acetabular version (p < 0.01), greater subtended angles superiorly and superior
      posteriorly (p = 0.01), higher pelvic incidence (p = 0.02), greater alpha angles
      and lower femoral neck-shaft angles compared to asymptomatic cams (p < 0.01) and
      controls (p < 0.01). The four predictors of symptomatic cam included antero
      superior alpha angle, femoral neck-shaft angle, acetabular depth, and pelvic
      incidence. In conclusion, this study illustrates that symptomatic hips had a
      greater amount of supero-posterior coverage; which would be the contact area
      between a radial cam and the acetabulum, when the hip is flexed to 90 degrees .
      Furthermore, individuals with symptomatic cam morphology had greater PI.
      Acetabular- and SP parameters should be part of the radiological assessment of
      femoro-acetabular impingement. (c) 2018 Orthopaedic Research Society. Published
      by Wiley Periodicals, Inc. J Orthop Res 36:1840-1848, 2018.

PMID- 29323747
TI  - Comprehensive intraoperative transesophageal echocardiography of anomalous left
      coronary artery from pulmonary artery: What to look for and where to look?
AB  - Anomalous origin of left coronary artery from pulmonary artery (ALCAPA) accounts
      for 0.4% of the congenital heart diseases. Comprehensive 2D and 3D
      transesophageal echocardiographic imaging of a well-collateralized subset of
      ALCAPA is described. A nonstandard short-axis view of both aorta and pulmonary
      arteries showed the origin of left coronary artery from the posterior sinus of
      the pulmonary artery and right coronary artery in its usual position. Pulse-wave
      interrogation of the coronary arteries showed the direction of flow in opposite
      directions. Using the real time-3D, the en-face views of the origins of both
      coronaries were also demonstrated.

PMID- 29323748
TI  - The gain-of-function mutation E76K in SHP2 promotes CAC tumorigenesis and induces
      EMT via the Wnt/beta-catenin signaling pathway.
AB  - SHP2 is encoded by the protein tyrosine phosphatase 11 (Ptpn11) gene. Several
      gain-of-function (GOF) mutations in Ptpn11 have been identified in human
      hematopoietic malignancies and solid tumors. In addition, the mutation rate for
      SHP2 is the highest for colorectal cancer (CRC) among solid tumors. The E76K GOF
      mutation is the most common and active SHP2 mutation; however, the pathogenic
      effects and function of this mutation in CRC tumor progression have not been well
      characterized. The Wnt/beta-catenin (CTNNB1) signaling pathway is crucial for
      CRC, and excessive activation of this pathway has been observed in several
      tumors. We used Ptpn11E76K conditional knock-in mice to study this GOF mutation
      in colitis-associated CRC (CAC) and used the CRC cell lines HT29 and HCT116 to
      determine the relationship between SHP2 and Wnt/beta-catenin signaling.
      Ptpn11E76K conditional knock-in mice exhibited aggravated inflammation and
      increased CAC tumorigenesis. In vitro, SHP2E76K and SHP2WT promoted malignant
      biological behaviors of CRC cells and induced epithelial-mesenchymal transition
      (EMT) via the Wnt/beta-catenin signaling pathway. Together, our results showed
      that SHP2E76K acts as an oncogene that promotes the tumorigenesis and metastasis
      of CRC.

PMID- 29323749
TI  - Synthesis and biological evaluation of phloroglucinol derivatives possessing
      alpha-glycosidase, acetylcholinesterase, butyrylcholinesterase, carbonic
      anhydrase inhibitory activity.
AB  - A series of novel phloroglucinol derivatives were designed, synthesized,
      characterized spectroscopically and tested for their inhibitory activity against
      selected metabolic enzymes, including alpha-glycosidase, acetylcholinesterase
      (AChE), butyrylcholinesterase (BChE), and human carbonic anhydrase I and II (hCA
      I and II). These compounds displayed nanomolar inhibition levels and showed Ki
      values of 1.14-3.92 nM against AChE, 0.24-1.64 nM against BChE, 6.73-51.10 nM
      against alpha-glycosidase, 1.80-5.10 nM against hCA I, and 1.14-5.45 nM against
      hCA II.

PMID- 29323750
TI  - Design, synthesis, and molecular docking of novel indole scaffold-based VEGFR-2
      inhibitors as targeted anticancer agents.
AB  - A series of new indole derivatives 1-18 was synthesized and tested for their
      cytotoxic activity on a panel of 60 tumor cell lines. Additionally, molecular
      docking was carried out to study their binding pattern and binding affinity in
      the VEGFR-2 active site using sorafenib as a reference VEGFR-2 inhibitor. Based
      on the molecular docking results, compounds 5a, 5b, 6, 7, 14b, 18b, and 18c were
      selected to be evaluated for their VEGFR-2 inhibitory activity. Compound 18b
      exhibited a broad-spectrum antiproliferative activity on 47 cell lines, with GI %
      ranging from 31 to 82.5%. Moreover, compound 18b was the most potent VEGFR-2
      inhibitor with an IC50 value of 0.07 MUM, which is more potent than that of
      sorafenib (0.09 MUM). A molecular docking study attributed the promising activity
      of this series to their hydrophobic interaction with the VEGFR-2 binding site
      hydrophobic side chains and their hydrogen bonding interaction with the key amino
      acids Glu885 and/or Asp1046.

PMID- 29323752
TI  - Congenital aortocaval fistula between right aortic sinus of Valsalva and superior
      vena cava: A rare case report.
AB  - Thoracic aortocaval fistula is a very rare cause of left to right shunt. Drainage
      of fistula into the superior vena cava (SVC) is very uncommon. Clinical symptoms
      depend on the size of the shunt. We report a rare case of an asymptomatic 27-year
      old woman with congenital aortocaval fistula to the SVC with a small amount of
      left to right shunt that was considered for serial medical follow-up.

PMID- 29323751
TI  - [18 F]AV-1451 clustering of entorhinal and cortical uptake in Alzheimer's
      disease.
AB  - OBJECTIVE: To use a cluster analysis of [18 F]AV-1451 tau-PET data to determine
      how subjects with Alzheimer's disease (AD) vary in the relative involvement of
      the entorhinal cortex and neocortex, and determine whether relative involvement
      of these two regions can help explain variability in age and clinical phenotype
      in AD. METHODS: We calculated [18 F]AV-1451 uptake in entorhinal cortex and
      neocortex in 62 amyloid-positive AD patients (39 typical and 23 atypical
      presentation). tau-PET (positron emission tomography) values were normalized to
      the cerebellum to create standard uptake value ratios (SUVRs). tau-PET SUVRs were
      log-transformed and clustered blinded to clinical information into three groups
      using K-median cluster analysis. Demographics, clinical phenotype, cognitive
      performance, and apolipoprotein e4 frequency were compared across clusters.
      RESULTS: The cluster analysis identified a cluster with low entorhinal and
      cortical uptake (ELo /CLo ), one with low entorhinal but high cortical uptake
      (ELo /CHi ), and one with high cortical and entorhinal uptake (EHi /CHi ).
      Clinical phenotype differed across clusters, with typical AD most commonly
      observed in the ELo /CLo and EHi /CHi clusters, and atypical AD most commonly
      observed in the ELo /CHi cluster. The ELo /CLo cluster had an older age at PET
      and onset than the other clusters. Apolipoprotein e4 frequency was lower in the
      ELo /CHi cluster. The EHi /CHi cluster had the worst memory impairment, whereas
      the ELo /CHi cluster had the worst impairment in nonmemory domains.
      INTERPRETATION: This study demonstrates considerable variability in [18 F]AV-1451
      tau-PET uptake in AD, but shows that a straightforward clustering based on
      entorhinal and cortical uptake maps well onto age and clinical presentation in
      AD. Ann Neurol 2018 Ann Neurol 2018;83:248-257.

PMID- 29323753
TI  - Associations of mitochondrial polymorphisms with sporadic colorectal adenoma.
AB  - Somatic mutations in mitochondrial DNA have been reported in colorectal
      adenomatous polyps (adenomas), the precursors to most colorectal cancers.
      However, there are no reports of associations of germline variation in
      mitochondrial DNA with adenoma risk. We investigated associations of germline
      polymorphisms in the displacement loop (D-loop) and non-D-loop region of the
      mitochondrial genome with incident, sporadic colorectal adenoma in three pooled
      colonoscopy-based case-control studies (n = 327 adenoma cases, 420 controls) that
      used identical methods for case and risk factor ascertainment. We sequenced a
      1124 bp fragment to identify all genetic variation in the mitochondrial D-loop
      region, and used the Sequenom platform to genotype 64 tagSNPs in the non-D-loop
      region. We used multivariable unconditional logistic regression to estimate
      associations of the polymorphisms with adenoma. The odds ratios (OR) for
      associations of four polymorphisms in the HV1 region (mt16294, mt16296, mt16278,
      mt16069) with adenoma were 2.30, 2.63, 3.34, and 0.56, respectively; all 95%
      confidence intervals (CI) excluded 1.0, however, after correction for multiple
      comparisons, none of the findings remained statistically significant. Similar
      results were found for six polymorphisms in the non-D-loop region. In the HV1
      region poly C tract, relative to those with 5 repeats, the ORs for those with
      fewer or more repeats were, respectively, 2.29 (95%CI 1.07-4.89) and 0.63 (95%CI
      0.36-1.08), but repeat numbers in the HV2 region were not associated with
      adenoma. These findings suggest that mitochondrial D-loop HV1 region
      polymorphisms may be associated with colorectal adenoma risk and support further
      investigation.

PMID- 29323755
TI  - Direct-acting antiviral regimens are safe and effective in the treatment of
      hepatitis C in simultaneous liver-kidney transplant recipients.
AB  - Hepatitis C (HCV) remains the single most common etiology of end-stage liver
      disease leading to simultaneous liver/kidney transplant (SLKT) and has worse post
      transplant survival compared to non-HCV patients. We aim to assess the
      effectiveness and tolerance of the all-oral direct-acting antiviral (DAA) agents
      with or without ribavirin (RBV) in the treatment of HCV recurrence post-SLKT.
      Thirty-four patients were studied retrospectively, composed predominantly of
      treatment-naive (73.5%) non-Caucasian (61.8%) males (82.4%) infected with
      genotype 1a (64.7%). 94.1% reached a sustained virologic response (SVR) after 24
      weeks (32/34 patients), without difference between 12 and 24 weeks of therapy.
      64.7% had no clinical side effects. Three deaths occurred, all unrelated to
      treatment. One patient had liver rejection; tacrolimus was increased and
      prednisone was initiated while HCV treatment was continued and the patient
      ultimately achieved SVR. No liver graft losses. No kidney rejection or losses. We
      demonstrated that DAA combinations with or without RBV result in a remarkable SVR
      rate and tolerated in the majority of the studied SLKT patients. It is safe to
      wait to treat until post-kidney transplant and therefore increase the donor pool
      for these patients. Our cohort is ethnically diverse, making our results
      generalizable.

PMID- 29323754
TI  - A rare cause of retinal artery embolism: Accessory mitral valve tissue.
AB  - A 42-year-old female patient was referred our clinic for investigation of a
      history of acute retinal artery occlusion. Transthoracic echocardiography showed
      a cyst-like, mobile formation on posterior mitral valve leaflet. 2D and real time
      3D transesophageal echocardiography showed a flexible circular mobile structure
      which was attached to posterior mitral valve leaflet. Echocardiographic
      appearance and morphological characteristics were suggestive of accessory mitral
      valve tissue.

PMID- 29323756
TI  - Juvenile Taiep rats have shorter dendritic trees in the dorsal field of the
      hippocampus without spatial learning disabilities.
AB  - Myelin mutant taiep rats show a progressive demyelination in the central nervous
      system due to an abnormal accumulation of microtubules in the cytoplasm and the
      processes on their oligodendrocytes. Demyelination is associated with
      electrophysiological alterations and the mutant had a progressive astrocytosis.
      The illness is associated with change in cytokine levels and in the expression of
      different nitric oxide synthase and concomitantly lipoperoxidation in several
      areas of the brain. However, until now there has been no detailed anatomical
      analysis of neurons in this mutant. The aim of this study was to analyze the
      dendritic morphology in the hippocampus using Golgi-Cox staining and spatial
      memory through Morris water maze test in young adult (3 months old) taiep rats
      and compare them with normal Sprague-Dawley. Our results showed that taiep rats
      have altered dendritic tree morphology in pyramidal neurons in the CA1 field of
      the hippocampus, but not in the CA3 region. These morphological changes did not
      produce a concomitant deficit in spatial memory acquisition or recall at this
      early stage of the disease. Our results suggest that impairment of dendritic
      morphology in the CA1 field of the hippocampus is a landmark of the pathology of
      this progressive multiple sclerosis model.

PMID- 29323758
TI  - Highly Stable, New, Organic-Inorganic Perovskite (CH3 NH3 )2 PdBr4 : Synthesis,
      Structure, and Physical Properties.
AB  - Lead halide perovskites have attracted striking attention recently, due to their
      appealing properties. However, toxicity and stability are two main factors
      restricting their application. In this work, a less toxic and highly stable Pd
      based hybrid perovskite was experimentally synthesized, after exploring different
      experimental conditions. This new hybrid organic-inorganic perovskite (CH3 NH3 )2
      PdBr4 was found to be an orthorhombic crystal (Cmce, Z=4) with lattice parameters
      a=8.00, b=7.99, c=18.89 A. The Cmce symmetry and lattice parameters were
      confirmed using Pawley refinement and the atoms positions were confirmed based on
      DFT calculation. This perovskite compound was determined to be a p-type
      semiconductor, with a resistivity of 102.9 kOmega cm, a carrier concentration of
      3.4 *1012  cm-3 , and a mobility of 23.4 cm2  (V s)-1 . Interestingly, XRD and
      UV/Vis measurements indicated that the phase of this new perovskite was
      maintained with an optical gap of 1.91 eV after leaving in air with a high
      humidity of 60 % for 4 days, and unchanged for months in N2 atmosphere; much more
      stable than most existing organic-inorganic perovskites. The synthesis and
      various characterizations of this work further the understanding of this (CH3 NH3
      )2 PdBr4 organic-inorganic hybrid perovskite material.

PMID- 29323757
TI  - Differentiation-associated urothelial cytochrome P450 oxidoreductase predicates
      the xenobiotic-metabolizing activity of "luminal" muscle-invasive bladder
      cancers.
AB  - Extra-hepatic metabolism of xenobiotics by epithelial tissues has evolved as a
      self-defence mechanism but has potential to contribute to the local activation of
      carcinogens. Bladder epithelium (urothelium) is bathed in excreted urinary
      toxicants and pro-carcinogens. This study reveals how differentiation affects
      cytochrome P450 (CYP) activity and the role of NADPH:P450 oxidoreductase (POR).
      CYP1A1 and CYP1B1 transcripts were inducible in normal human urothelial (NHU)
      cells maintained in both undifferentiated and functional barrier-forming
      differentiated states in vitro. However, ethoxyresorufin O-deethylation (EROD)
      activity, the generation of reactive BaP metabolites and BaP-DNA adducts, were
      predominantly detected in differentiated NHU cell cultures. This gain-of-function
      was attributable to the expression of POR, an essential electron donor for all
      CYPs, which was significantly upregulated as part of urothelial differentiation.
      Immunohistology of muscle-invasive bladder cancer (MIBC) revealed significant
      overall suppression of POR expression. Stratification of MIBC biopsies into
      "luminal" and "basal" groups, based on GATA3 and cytokeratin 5/6 labeling, showed
      POR over-expression by a subgroup of the differentiated luminal tumors. In
      bladder cancer cell lines, CYP1-activity was undetectable/low in basal PORlo T24
      and SCaBER cells and higher in the luminal POR over-expressing RT4 and RT112
      cells than in differentiated NHU cells, indicating that CYP-function is related
      to differentiation status in bladder cancers. This study establishes POR as a
      predictive biomarker of metabolic potential. This has implications in bladder
      carcinogenesis for the hepatic versus local activation of carcinogens and as a
      functional predictor of the potential for MIBC to respond to prodrug therapies.

PMID- 29323759
TI  - Barriers and Solutions to Delivery of Intensive Care Unit Nutrition Therapy.
AB  - Despite recommendations for early enteral nutrition (EN) in critically ill
      patients, numerous factors contribute to incomplete delivery of EN, including
      insufficient nutrition risk screening in critically ill patients,
      underutilization of enteral feeding protocols, fixed rate-based enteral infusion
      targets with frequent EN interruption, and suboptimal provider practices
      regarding nutrition support therapy. The purpose of this narrative review is to
      identify common barriers to optimizing and delivering nutrition in critically ill
      patients, and suggest strategies and solutions to overcome barriers.

PMID- 29323760
TI  - Donor CD163 and nestin-positive cells predict graft function in living donor
      liver transplant.
AB  - AIMS: To evaluate the effect of donor liver resident mesenchymal cells, M2
      macrophages on liver graft outcome after living donor liver transplantation.
      MATERIALS AND METHODS: Seventy donor biopsies were included in the study.
      Outcomes at day 3, 7, 30, and 180 postliver transplantation were assessed.
      Mesenchymal stem cells and M2 macrophages in donor liver biopsies were evaluated.
      RESULTS: Mean age of recipients was 40.9 +/- 13.6 years. Sex mismatched
      transplants were 44 (M->F = 9; F->M = 35). On area under receiver operative curve
      analysis, donor biopsy (DB) nestin >=3 and CD 163 >= 32/200x at day 3; CD163 >=
      32 at day 7; CD 163 > 32, pRBC of <6.5 units at day 30, and DB nestin >=3, CD 163
      >= 32 and pRBC<6.5 units at day 180 predicted adequate graft functions. On
      multivariate analysis, higher DB nestin (P = .009) and lower cryoprecipitate (P =
      .009) usage at day 3, higher DB CD163 (P = .006) at day 7, higher DB CD163 (P =
      .018) and reduced transfusion of packed cell (pRBC) (P = .014) at day 30 and
      higher DB nestin (P = .011), higher CD163 (P = .009), and reduced pRBC (P = .045)
      at day 180 were the predictors of better outcome. CONCLUSIONS: Donor liver biopsy
      nestin+ and CD163+ can predict early graft outcome in living donor liver
      transplantation.

PMID- 29323762
TI  - Pentacene Dimers as a Critical Tool for the Investigation of Intramolecular
      Singlet Fission.
AB  - Singlet fission (SF) involves the spontaneous splitting of a photoexcited singlet
      state into a pair of triplets, and it holds great promise toward the realization
      of more efficient solar cells. Although the process of SF has been known since
      the 1960s, debate regarding the underlying mechanism continues to this day,
      especially for molecular materials. A number of different chromophores have been
      synthesized and studied in order to better understand the process of SF. These
      previous reports have established that pentacene and its derivatives are
      especially well-suited for the study of SF, since the energetic requirement E(S1
      )>=2E(T1 ) is fulfilled rendering the process exothermic and unidirectional.
      Dimeric pentacene derivatives, in which individual pentacene chromophores are
      tethered by a "spacer", have emerged as the system of choice toward exploring the
      mechanism of intramolecular singlet fission (iSF). The dimeric structure, and in
      particular the spacer, allows for controlling and tuning the distance, geometric
      relationship, and electronic coupling between the two pentacene moieties. This
      Minireview describes recent advances using pentacene dimers for the investigation
      of iSF.

PMID- 29323763
TI  - Calcium-Responsive Liposomes via a Synthetic Lipid Switch.
AB  - Liposomal drug delivery would benefit from enhanced control over content release.
      Here, we report a novel avenue for triggering release driven by chemical
      composition using liposomes sensitized to calcium-a target chosen due to its key
      roles in biology and disease. To demonstrate this principle, we synthesized
      calcium-responsive lipid switch 1, designed to undergo conformational changes
      upon calcium binding. The conformational change perturbs membrane integrity,
      thereby promoting cargo release. This was shown through fluorescence-based
      release assays via dose-dependent response depending on the percentage of 1 in
      liposomes, with minimal background leakage in controls. DLS experiments indicated
      dramatic changes in particle size upon treatment of liposomes containing 1 with
      calcium. In a comparison of ten naturally occurring metal cations, calcium
      provided the greatest release. Finally, STEM images showed significant changes in
      liposome morphology upon treatment of liposomes containing 1 with calcium. These
      results showcase lipid switches driven by molecular recognition principles as an
      exciting avenue for controlling membrane properties.

PMID- 29323764
TI  - Integrative neuro-humoral regulation of oxytocin neuron activity in pregnancy and
      lactation.
AB  - Oxytocin is required for normal birth and lactation. Oxytocin is synthesised by
      hypothalamic supraoptic and paraventricular nuclei neurons and is released into
      the circulation from the posterior pituitary gland. Under basal conditions,
      circulating oxytocin levels are relatively constant but during birth and
      lactation, pulsatile oxytocin release triggers rhythmic contraction of the uterus
      during birth and milk ejection during suckling. Oxytocin levels are principally
      determined by the pattern of action potential firing that is, in turn, determined
      by the interplay between the intrinsic properties of the oxytocin neurons,
      regulation of their excitability by surrounding glia as well as by synaptic drive
      from their afferent inputs. During birth and suckling, oxytocin neurons fire high
      frequency bursts of action potentials that are coordinated across the population
      of neurons and these bursts underpin the pulsatile secretion of oxytocin required
      for normal birth and lactation. Neuroglial regulation of oxytocin neurons changes
      during pregnancy to favour burst firing. However, these changes still require
      afferent input activity to drive activity. While it has long been known that
      noradrenergic inputs to oxytocin neurons are activated during birth and
      lactation, the involvement of other afferent inputs is less clear. Here, we
      provide a brief overview of the current understanding of the mechanisms that
      regulate oxytocin neuron activity during pregnancy and lactation, and focus on
      recent evidence from our laboratory identifying an input that increases
      kisspeptin production to excite oxytocin neurons in late pregnancy. This article
      is protected by copyright. All rights reserved.

PMID- 29323761
TI  - Chronic Critical Illness: Application of What We Know.
AB  - Over the last decade, chronic critical illness (CCI) has emerged as an epidemic
      in intensive care unit (ICU) survivors worldwide. Advances in ICU technology and
      implementation of evidence-based care bundles have significantly decreased early
      deaths and have allowed patients to survive previously lethal multiple organ
      failure (MOF). Many MOF survivors, however, experience a persistent dysregulated
      immune response that is causing an increasingly predominant clinical phenotype
      called the persistent inflammation, immunosuppression, and catabolism syndrome
      (PICS). The elderly are especially vulnerable; thus, as the population ages the
      prevalence of this CCI/PICS clinical trajectory will undoubtedly grow.
      Unfortunately, there are no proven therapies to prevent PICS, and multimodality
      interventions will be required. The purpose of this review is to: (1) discuss CCI
      as it relates to PICS, (2) identify the burden on healthcare and poor outcomes of
      these patients, and (3) describe possible nutrition interventions for the
      CCI/PICS phenotype.

PMID- 29323765
TI  - Human papillomavirus and nasopharyngeal cancer.
AB  - BACKGROUND: There are no existing high-volume studies characterizing human
      papillomavirus (HPV)-associated nasopharyngeal cancer (NPC). METHODS: The
      National Cancer Data Base (NCDB) was queried for NPC with known HPV (2004-2013).
      Logistic regression ascertained factors associated with HPV-positivity. Kaplan
      Meier overall survival (OS) was evaluated between HPV-positive and HPV-negative
      cohorts; Cox proportional hazards modeling assessed factors associated with OS.
      Patients with nonmetastatic disease receiving definitive chemoradiotherapy
      underwent propensity-matched OS analysis. RESULTS: Altogether, 956 patients were
      analyzed (32% HPV-positive and 68% HPV-negative). Median follow-up was 23 months
      (range 0-67 months). The patients with HPV-positive disease were younger, less
      likely to be uninsured, lived in more educated areas, and presented with more
      advanced T (but not N/overall) classification. Median OS for HPV-positive and HPV
      negative groups were 50 and 43 months, respectively (P = .171). The HPV status
      did not independently predict for OS (P = .183). No OS differences were observed
      after propensity matching (P = .734). CONCLUSION: In what we believe as the only
      large study of HPV-associated NPC, HPV neither correlates with nor predicts
      survival in NPC. Owing to the difficulty of addressing causality in database
      studies, further work must corroborate the findings herein.

PMID- 29323766
TI  - Acupuncture in hospice settings: A qualitative exploration of patients'
      experiences.
AB  - Whilst acupuncture has the potential to impact on many aspects of health and well
      being, including end-of-life care, there is little research regarding patients'
      experiences of its effects within the context of palliative care in hospice
      settings. The aim of this study was to address this gap, by exploring patients'
      experiences of acupuncture within this setting. In-depth, semi-structured
      interviews were conducted with a sample of eighteen patients who had received
      acupuncture as part of hospice care. Transcription of data, with thematic
      analysis, identified two overarching themes: (1) participant perceptions of the
      effects of acupuncture including pain control, improved physical and emotional
      health, spiritual well-being and awareness of health as a holistic phenomenon;
      and (2) factors which participants believed enabled acupuncture to have these
      effects including the quality of the practitioner relationship, engagement of
      participants in the process of their treatment and prior expectations that
      acupuncture could work. Acupuncture was found to be a highly acceptable,
      accessible and popular treatment with positive holistic effects reported across
      the domains of physical, mental and spiritual health and no serious adverse
      effects. By enabling awareness of the holistic nature of health and well-being,
      acupuncture was experienced as having the potential to contribute to a better
      death, an emergent theory that needs testing in further studies. In the
      meanwhile, the results of this study offer encouragement to hospices currently
      providing or considering investing in acupuncture provision.

PMID- 29323767
TI  - High land-use intensity exacerbates shifts in grassland vegetation composition
      after severe experimental drought.
AB  - Climate change projections anticipate increased frequency and intensity of
      drought stress, but grassland responses to severe droughts and their potential to
      recover are poorly understood. In many grasslands, high land-use intensity has
      enhanced productivity and promoted resource-acquisitive species at the expense of
      resource-conservative ones. Such changes in plant functional composition could
      affect the resistance to drought and the recovery after drought of grassland
      ecosystems with consequences for feed productivity resilience and environmental
      stewardship. In a 12-site precipitation exclusion experiment in upland grassland
      ecosystems across Switzerland, we imposed severe edaphic drought in plots under
      rainout shelters and compared them with plots under ambient conditions. We used
      soil water potentials to scale drought stress across sites. Impacts of
      precipitation exclusion and drought legacy effects were examined along a gradient
      of land-use intensity to determine how grasslands resisted to, and recovered
      after drought. In the year of precipitation exclusion, aboveground net primary
      productivity (ANPP) in plots under rainout shelters was -15% to -56% lower than
      in control plots. Drought effects on ANPP increased with drought severity,
      specified as duration of topsoil water potential psi < -100 kPa, irrespective of
      land-use intensity. In the year after drought, ANPP had completely recovered, but
      total species diversity had declined by -10%. Perennial species showed elevated
      mortality, but species richness of annuals showed a small increase due to
      enhanced recruitment. In general, the more resource-acquisitive grasses increased
      at the expense of the deeper-rooted forbs after drought, suggesting that
      community reorganization was driven by competition rather than plant mortality.
      The negative effects of precipitation exclusion on forbs increased with land-use
      intensity. Our study suggests a synergistic impact of land-use intensification
      and climate change on grassland vegetation composition, and implies that biomass
      recovery after drought may occur at the expense of biodiversity maintenance.

PMID- 29323768
TI  - Copper-Catalyzed Enantioselective Arylative Desymmetrization of Prochiral
      Cyclopentenes with Diaryliodonium Salts.
AB  - A copper-catalyzed enantioselective arylative desymmetrization of prochiral
      cyclopentenes with diaryliodonium salts was developed. In the presence of a
      catalytic amount of a chiral copper-bisoxazoline complex, which was generated in
      situ, the reaction of 4-substituted or 4,4-disubstituted cyclopent-1-enes with
      diaryliodonium hexafluoroarsenates afforded the chiral arylated products in good
      yields with excellent enantioselectivity. A cyclohexyl-containing Box ligand was
      essential for the high enantioselectivity. Transformation of the enantiomerically
      enriched adducts into other chiral building blocks is also documented.

PMID- 29323769
TI  - Systolic heart failure after liver transplantation: Incidence, predictors, and
      outcome.
AB  - Although most patients presenting for liver transplantation have normal left
      ventricular function, some develop left ventricular failure after
      transplantation. The primary objective of our study was to determine the
      predictors of systolic heart failure (HF) occurring immediately after liver
      transplantation. Its etiology, prospects of recovery, and factors associated with
      nonrecovery were also studied. Liver transplantations performed at our
      institution from January 2006 to February 2015 were evaluated using prospectively
      collected institutional registries. Patients with echocardiographically
      documented decline in ejection fraction to <45% within 6 months after liver
      transplantation were identified. Four controls were chosen per case: matched for
      age, gender, transplant year, and model for end-stage liver disease score.
      Conditional multivariable logistic regression was used for primary analysis and
      nonparametric tests for comparison between groups. In a cohort of 1284 adult
      patients, 45 cases and 180 controls were identified. Diastolic dysfunction (DD)
      was an independent predictor (OR 5.26, 95% CI 1.03-28.57, P = .04) of systolic HF
      in multivariable analysis. Stress-induced cardiomyopathy was the most common
      etiology. Left ventricular function recovered in 21 patients. Pretransplant DD
      decreased the chances of recovery (P = .05). In conclusion, patients with
      pretransplant DD need close post-transplant follow-up for timely identification
      of HF.

PMID- 29323770
TI  - Human papillomavirus in the nasopharynx: A true entity?

PMID- 29323771
TI  - Association of IGFN1 variant with polypoidal choroidal vasculopathy.
AB  - BACKGROUND: Polypoidal choroidal vasculopathy (PCV) and neovascular age-related
      macular degeneration (nAMD) share a similar phenotype but are different in their
      clinical manifestations, responses to treatment and prognosis. Whether PCV is a
      subtype of AMD or a distinct entity from nAMD remains unknown. Therefore, we
      performed a whole-exome sequencing based association analysis to compare the
      genetic architecture of PCV and nAMD in Han Chinese. METHODS: Whole-exome
      sequencing analysis was performed on 21 nAMD cases, 20 PCV cases and 20 healthy
      controls. As a follow-up validation, 145 nAMD cases, 160 PCV cases and 193
      controls were genotyped using the Sequenom MassARRAY platform (Sequenom, San
      Diego, CA, USA). RESULTS: A novel variant, c.6196A>G in the IGFN1 gene, was
      significantly associated with only PCV (combined p = 7.1 * 10-11 , odds ratio =
      9.44), but not with nAMD (combined p = 0.683, odds ratio = 1.30). The minor
      allele G conferred an increased risk of PCV. CONCLUSIONS: The findings of the
      present study indicate that, although some of the susceptibility loci are shared
      between PCV and nAMD, a unique genetic signature may decide the pathogenesis of
      PCV.

PMID- 29323773
TI  - Direct Fiber-Reinforced Interim Fixed Partial Dentures: Six-Year Survival Study.
AB  - PURPOSE: Mechanical and optical studies of glass fiber composites have revealed
      great resistance and satisfactory bonds between the glass fibers and composite
      resins. This study aimed to evaluate the long-term survival of anterior and
      posterior direct glass fiber-reinforced composite (FRC) fixed partial dentures
      (FPD). MATERIALS AND METHODS: Twenty-three patients (9 men, 14 women) aged 18 to
      67 received 23 d-FRC-FPDs. The frameworks of the FPDs were unidirectional pre
      impregnated glass fibers (ever Stick C&B). The retainers were inlay composite
      resin retainers (n1 = 19) and composite resin wings (n2 = 4). The FPD that used
      inlay retainers and composite resin wing retainers was called the hybrid design.
      The mean follow-up period was 4.91 years with 12-month check-ups performed by two
      independent operators. The survival rates of the glass fiber FPDs were
      determined. RESULTS: Six-year survival rates for the two types of FPDs were 94.7%
      for the inlay retainer type versus 25% for the hybrid type, with a statistically
      significant difference (log-rank test chi2 (1) = 11.422, p = 0.001). The inlay
      retainers were functional, with only one patient with a fracture line in the
      connector held by the glass fibers. Kaplan-Meier survival curves were drawn to
      show the difference between the two types of retainers. CONCLUSION: According to
      the results of this study, these long-term interim FRC-FPD were resistant enough
      to allow mastication, minimally invasive and also esthetic, with inlay composite
      retainers as the better solution.

PMID- 29323774
TI  - Obesity Impairs Oligopeptide/Amino Acid-Induced Ghrelin Release and Smooth Muscle
      Contractions in the Human Proximal Stomach.
AB  - SCOPE: The satiation properties of proteins involve effects on gut peptide
      release and gastrointestinal motility which may be altered during obesity. This
      study compares the in vitro response and role of amino acid (AA) taste receptors
      (TASR) in the effect of AAs and a casein hydrolysate on ghrelin release and
      smooth muscle (SM) contractions in the proximal gut of lean and obese patients.
      METHODS AND RESULTS: Basal ghrelin release, measured from mucosal segments, is
      maximal in the fundus and decreased distally. Obesity selectively impaires the
      stimulatory effect of a casein hydrolyaste on ghrelin release in the fundus but
      does not affect its inhibitory effect in the small intestine (SI). The SM
      contractions induced by a casein hydrolysate and AAs are stronger in strips from
      the SI than from the fundus but are reduced in the stomach of obese patients. The
      region-dependent expression of AA-TASRs in the mucosa and SM layer is affected by
      obesity. Most of the AA-induced responses are reduced by the umami antagonist,
      lactisole. l-Met-induced responses involve bitter taste receptors. CONCLUSION:
      Region-specific targeting of AA taste receptors on both enteroendocrine and SM
      cells with specific AA-enriched diets might be a useful strategy to combat
      obesity as well as hypomotility disorders.

PMID- 29323775
TI  - Van't Hoff analysis in chiral chromatography.
AB  - The present review discusses the theory and application of van't Hoff analysis in
      chiral chromatography, with main focus on liquid chromatography. The topics
      considered include the physical meaning of van't Hoff equation's parameters,
      interpretation of thermodynamic data in terms of retention and enantioseparation
      mechanisms, abnormal behavior of van't Hoff plots, and best practices to avoid
      biased results.

PMID- 29323772
TI  - The role of Nrf2 signaling in counteracting neurodegenerative diseases.
AB  - The transcription factor Nrf2 (nuclear factor-erythroid 2 p45-related factor 2)
      functions at the interface of cellular redox and intermediary metabolism. Nrf2
      target genes encode antioxidant enzymes, and proteins involved in xenobiotic
      detoxification, repair and removal of damaged proteins and organelles,
      inflammation, and mitochondrial bioenergetics. The function of Nrf2 is altered in
      many neurodegenerative disorders, such as Huntington's disease, Alzheimer's
      disease, amyotrophic lateral sclerosis, and Friedreich's ataxia. Nrf2 activation
      mitigates multiple pathogenic processes involved in these neurodegenerative
      disorders through upregulation of antioxidant defenses, inhibition of
      inflammation, improvement of mitochondrial function, and maintenance of protein
      homeostasis. Small molecule pharmacological activators of Nrf2 have shown
      protective effects in numerous animal models of neurodegenerative diseases, and
      in cultures of human cells expressing mutant proteins. Targeting Nrf2 signaling
      may provide a therapeutic option to delay onset, slow progression, and ameliorate
      symptoms of neurodegenerative disorders.

PMID- 29323776
TI  - Remineralization of Natural Human Carious Dentin Lesions with an Experimental
      Whisker-Reinforced Atraumatic Restorative Treatment Composite.
AB  - PURPOSE: To evaluate the remineralization of natural human dentin caries with an
      experimental whisker-reinforced Atraumatic Restorative Treatment (ART) composite.
      MATERIALS AND METHODS: Teeth with moderate active dentin caries were prepared
      with caries-disclosing dye and hand instruments, restored with ART or resin
      modified glass ionomer cement (RM-GIC), and then wet sliced into 120-MUm sections
      with 15 sections in each group. After taking transverse microradiographs and
      implementing digital image analysis to determine the "mineral-loss-before," each
      section was incubated in artificial saliva solution (pH = 7.0) for 4 weeks and 8
      weeks with 1 hour each workday in demineralization solution (pH = 4.3).
      Transverse microradiographs of each section were retaken, and the "mineral-loss
      after" was determined. The remineralization was calculated from [1-("mineral-loss
      after"/"mineral-loss-before")] * 100%. Results were statistically analyzed with a
      repeated-measures ANOVA with one within-subject factor (time: 4 and 8 weeks) and
      one between-subject factor (material: ART and RM-GIC) (alpha = 0.05). RESULTS:
      The statistical analysis indicated that ART composite resulted in significantly
      higher remineralization than the RM-GIC (p <= 0.05). For the remineralization of
      each material, there was a statistical difference between 4 weeks and 8 weeks (p
      <= 0.05). CONCLUSIONS: This experimental ART composite remineralized natural
      human dentin caries better than the RM-GIC.

PMID- 29323777
TI  - Optimization of the surface modification process of cross-linked polythiol-coated
      chiral stationary phases synthesized by a two-step thiol-ene click reaction.
AB  - A new platform technology for the preparation of stable chiral stationary phases
      was successfully optimized. The chiral selector tert-butylcarbamoylquinine was
      firstly covalently connected to the polymer poly(3-mercaptopropyl)methylsiloxane
      by thiol-ene click reaction. Secondly, the quinine carbamate functionalized
      polysiloxane conjugate was coated onto the surface of vinyl modified silica
      particles and cross-linked via thiol-ene click reaction. The amount of
      polysiloxane, chiral selector, radical initiator, reaction solvent (chloroform
      and methanol), reaction time, and pore size of the supporting silica particles
      were varied and systematically optimized in terms of achievable plate numbers
      while maintaining simultaneously enantioselectivity. The optimization was based
      on elemental analysis data, chromatographic results, and H/u-curves (Van Deemter)
      of the resultant chiral stationary phases. The results suggest that better
      chromatographic efficiency (higher plate numbers) at equal enantioselectivity can
      be achieved with methanol (a poor solvent for the polysiloxane that is dispersed
      rather than dissolved) and a lower film thickness of quinine carbamate
      functionalized polysiloxane. In this study, chiral stationary phases based on 100
      A silica slightly outperformed 200 A silica particles (each 5 MUm). The optimized
      two step material exhibited significantly reduced mass transfer resistance
      compared to the one step material and equal performance as a brush-type chiral
      stationary phase.

PMID- 29323778
TI  - Antibiotics versus no antibiotics in the treatment of acute uncomplicated
      diverticulitis - a systematic review and meta-analysis.
AB  - BACKGROUND: Acute uncomplicated diverticulitis (AUD) is common and antibiotics
      are the cornerstone of traditional conservative management. This approach lacks
      clear evidence base and studies have recently suggested that avoidance of
      antibiotics is a safe and efficacious way to manage AUD. The aim of this
      systematic review is to determine the safety and efficacy of treating AUD without
      antibiotics. METHODS: A systematic search of Embase, Cochrane library, MEDLINE,
      Science Citation Index Expanded, and ClinicalTrials. gov was performed. Studies
      comparing antibiotics versus no antibiotics in the treatment of AUD were
      included. Meta-analysis was performed using the random effects model with the
      primary outcome measure being diverticulitis-associated complications. Secondary
      outcomes were readmission rate, diverticulitis recurrence, mean hospital stay,
      requirement for surgery and requirement for percutaneous drainage. RESULTS: Eight
      studies were included involving 2469 patients; 1626 in the non-antibiotic group
      (NAb) and 843 in the antibiotic group (Ab). There was a higher complication rate
      in the Ab group however this was not significant (1.9% versus 2.6%) with a
      combined risk ratio (RR) of 0.63 (95% CI, 0.25 to 1.57, p=0.32). There was a
      shorter mean length of hospital stay in the Nab group (standard mean difference
      of -1.18 (95% CI, -2.34 to -0.03 p= 0.04). There was no significant difference in
      readmission, recurrence and surgical intervention rate or requirement for
      percutaneous drainage. CONCLUSION: Treatment of AUD without antibiotics may be
      feasible with outcomes that are comparable to antibiotic treatment and with
      potential benefits for patients and the NHS. Large scale randomised multicentre
      studies are needed. This article is protected by copyright. All rights reserved.

PMID- 29323779
TI  - Effect of Different Liners on Fracture Resistance of Premolars Restored with
      Conventional and Short Fiber-Reinforced Composite Resins.
AB  - PURPOSE: To see whether applying four different liners under short fiber
      reinforced composite (SFRC), everX Posterior, compared to conventional composite
      resin, Z250, affected their strengthening property in premolar MOD cavities.
      MATERIALS AND METHODS: Mesio-occluso-distal (MOD) cavities were prepared in 120
      sound maxillary premolars divided into 10 groups (n = 12) in terms of two
      composite resin types and 4 liners or no liner. For each composite resin, in 5
      groups no liner, resin-modified glass ionomer (RMGI), conventional flowable
      composite (COFL), self-adhesive flowable composite resin (SAFL), and self
      adhesive resin cement (SARC) were applied prior to restoring incrementally. After
      water storage and thermocycling, static fracture resistance was tested. Data (in
      Newtons) were analyzed using two-way ANOVA (alpha = 0.05). RESULTS: Fracture
      resistance was significantly affected by composite resin type (p = 0.02), but not
      by the liner (p > 0.05). The interaction of the two factors was not statistically
      significant (p > 0.05). SFRC exhibited higher fracture strength (1470 +/- 200 N)
      compared to conventional composite resin (1350 +/- 290), irrespective of the
      application of liners. Application of SARC and SAFL liners led to a higher number
      of restorable fractures for both composite resins. CONCLUSIONS: The four liners
      can be used without interfering with the higher efficacy of SFRC, compared to
      conventional composite resins, to improve the fracture strength of premolar MOD
      cavities.

PMID- 29323780
TI  - Nurses' Perceptions on the Overuse of Health Services: A Qualitative Study.
AB  - PURPOSE: To examine whether nurses in Israel think there is overuse of health
      services, the reasons behind the issue, and ways to reduce the overuse. DESIGN:
      This was a qualitative study using semistructured interviews. A convenience
      sample of community care nurses from health clinics across Israel was
      interviewed. Interviews focused on common areas of overuse, outcomes of overuse,
      causes of overuse, and potential ways to address the issue. Interviews were
      recorded, transcribed, and analyzed thematically. FINDINGS: Overuse of
      antibiotics, imaging, blood tests, and prenatal surveillance were cited as main
      areas of health service overuse. Participants stated that negative outcomes of
      overuse could be seen at patient, health system, and population levels. Factors
      influencing overuse included patient satisfaction, physician fears, and
      insecurities. Potential interventions included improving physicians' diagnostic
      confidence, increasing appointment times, providing patients with more treatment
      information, and implementing a unified computerized system across medical
      institutions. CONCLUSIONS: Nurses mentioned physicians and patients as main
      actors in influencing overuse; hence, those populations should be researched
      further. The health system was identified as the responsible party to address the
      issue. Health system leaders must consider potential barriers, and investigate
      interventions that match current culture and context within the health system.
      CLINICAL RELEVANCE: Nurses can play an essential role in limiting overuse and
      mitigating subsequent harms to patients.

PMID- 29323781
TI  - Soil phosphorus does not keep pace with soil carbon and nitrogen accumulation
      following woody encroachment.
AB  - Soil carbon, nitrogen, and phosphorus cycles are strongly interlinked and
      controlled through biological processes, and the phosphorus cycle is further
      controlled through geochemical processes. In dryland ecosystems, woody
      encroachment often modifies soil carbon, nitrogen, and phosphorus stores,
      although it remains unknown if these three elements change proportionally in
      response to this vegetation change. We evaluated proportional changes and spatial
      patterns of soil organic carbon (SOC), total nitrogen (TN), and total phosphorus
      (TP) concentrations following woody encroachment by taking spatially explicit
      soil cores to a depth of 1.2 m across a subtropical savanna landscape which has
      undergone encroachment by Prosopis glandulosa (an N2 fixer) and other woody
      species during the past century in southern Texas, USA. SOC and TN were coupled
      with respect to increasing magnitudes and spatial patterns throughout the soil
      profile following woody encroachment, while TP increased slower than SOC and TN
      in topmost surface soils (0-5 cm) but faster in subsurface soils (15-120 cm).
      Spatial patterns of TP strongly resembled those of vegetation cover throughout
      the soil profile, but differed from those of SOC and TN, especially in subsurface
      soils. The encroachment of woody species dominated by N2 -fixing trees into this
      P-limited ecosystem resulted in the accumulation of proportionally less soil P
      compared to C and N in surface soils; however, proportionally more P accrued in
      deeper portions of the soil profile beneath woody patches where alkaline soil pH
      and high carbonate concentrations would favor precipitation of P as relatively
      insoluble calcium phosphates. This imbalanced relationship highlights that the
      relative importance of biotic vs. abiotic mechanisms controlling C and N vs. P
      accumulation following vegetation change may vary with depth. Our findings
      suggest that efforts to incorporate effects of land cover changes into coupled
      climate-biogeochemical models should attempt to represent C-N-P imbalances that
      may arise following vegetation change.

PMID- 29323782
TI  - The Effect of Surface Treatments on the Mechanical and Optical Behaviors of
      CAD/CAM Restorative Materials.
AB  - PURPOSE: To evaluate the effect of different surface treatments on mechanical and
      optical properties of lithium disilicate ceramic (IPS e.max CAD), 2 resin
      nanoceramics (Lava Ultimate, GC Cerasmart), and polymer-infiltrated ceramic
      network material (Vita Enamic). MATERIALS AND METHODS: CAD/CAM blocks were
      sectioned into 4 * 1 * 14 mm3 bars for three-point bending test and 1 * 8 * 8 mm3
      square specimens were obtained for color and translucency measurements. Bar
      shaped and square specimens were divided into five groups according to the
      surface treatment method as: control (no treatment), hydrofluoric acid etching,
      airborne-particle abrasion, 2 W and 3 W Er,Cr:YSGG laser irradiation (n = 10).
      Three-point bending test was carried out on a universal test machine with a 1
      mm/min crosshead speed. Color and translucency measurements were performed with a
      spectrophotometer and repeated after surface treatments. Flexural strength,
      translucency parameter, and DeltaE values were calculated and data were
      statistically analyzed using one-way ANOVA and Bonferroni post hoc tests. DeltaE
      values >1.2 and >2.7 were considered as perceptible and unacceptable,
      respectively. RESULTS: All surface treatment methods decreased the flexural
      strength of all tested materials (P < 0.05) except for 2 W laser-irradiated and
      airborne-particle abraded Vita Enamic and 2 W laser irradiated Lava Ultimate (P >
      0.05). Color changes of lithium disilicate specimens were not perceptible except
      for airborne-particle abraded specimens. All DeltaE values of resin-based
      materials were above the perceptibility threshold. Acid-etched and 3 W laser
      irradiated GC Vita Enamic specimens revealed unacceptable color changes. The
      translucencies of resin-based materials significantly decreased after all surface
      treatment applications. CONCLUSIONS: Surface treatments affected the flexural
      strength and optical properties of CAD/CAM restorative materials. Er,Cr:YSGG
      laser irradiation with 2 W energy level may be an alternative surface treatment
      method for CAD/CAM materials.

PMID- 29323783
TI  - Chiral ligand exchange countercurrent chromatography: Enantioseparation of amino
      acids.
AB  - This work deals with the enantioseparation of alpha-amino acids by chiral ligand
      exchange high-speed countercurrent chromatography using N-n-dodecyl-l
      hydroxyproline as a chiral ligand and copper(II) as a transition metal ion. A
      biphasic solvent system composed of n-hexane/n-butanol/aqueous phase with
      different volume ratios was selected for each alpha-amino acid. The
      enantioseparation conditions were optimized by enantioselective liquid-liquid
      extractions, in which the main influence factors, including type of chiral
      ligand, concentration of chiral ligand and transition metal ion, separation
      temperature, and pH of the aqueous phase, were investigated for racemic
      phenylalanine. Altogether, we tried to enantioseparate 15 racemic alpha-amino
      acids by the analytical countercurrent chromatography, of which only five of them
      could be successfully enantioseparated. Different elution sequence for
      phenylalanine enantiomer was observed compared with traditional liquid
      chromatography and the proposed interactions between chiral ligand, transition
      metal ion (Cu2+ ), and enantiomer are discussed.

PMID- 29323784
TI  - Nano Silver Vanadate AgVO3 : Synthesis, New Functionalities and Applications.
AB  - Silver vanadates have been widely investigated because of their many interesting
      properties and their potential use in several applications. In addition to this,
      a large number of groups have investigated silver vanadates in the form of
      nanostructures. Here, we address first the synthesis and properties of nanosilver
      vanadate. Different techniques, such as precipitation, thermal decomposition,
      hydrothermal treatment, and sol-gel, are among the methods that have been
      employed for the controlled synthesis of silver vanadate. The use of nanosilver
      vanadate for the development of novel electronic devices, catalysts, and
      antibacterial agents for industry and biomedical applications will then be
      discussed. In this sense, the present review highlights the major advances
      regarding the synthesis, properties and applications of nanostructured silver
      vanadates.

PMID- 29323785
TI  - Crystal structure of the DNA-binding domain of the LysR-type transcriptional
      regulator CbnR in complex with a DNA fragment of the recognition-binding site in
      the promoter region.
AB  - : LysR-type transcriptional regulators (LTTRs) are among the most abundant
      transcriptional regulators in bacteria. CbnR is an LTTR derived from Cupriavidus
      necator (formerly Alcaligenes eutrophus or Ralstonia eutropha) NH9 and is
      involved in transcriptional activation of the cbnABCD genes encoding
      chlorocatechol degradative enzymes. CbnR interacts with a cbnA promoter region of
      approximately 60 bp in length that contains the recognition-binding site (RBS)
      and activation-binding site (ABS). Upon inducer binding, CbnR seems to undergo
      conformational changes, leading to the activation of the transcription. Since the
      interaction of an LTTR with RBS is considered to be the first step of the
      transcriptional activation, the CbnR-RBS interaction is responsible for the
      selectivity of the promoter to be activated. To understand the sequence
      selectivity of CbnR, we determined the crystal structure of the DNA-binding
      domain of CbnR in complex with RBS of the cbnA promoter at 2.55 A resolution. The
      crystal structure revealed details of the interactions between the DNA-binding
      domain and the promoter DNA. A comparison with the previously reported crystal
      structure of the DNA-binding domain of BenM in complex with its cognate RBS
      showed several differences in the DNA interactions, despite the structural
      similarity between CbnR and BenM. These differences explain the observed promoter
      sequence selectivity between CbnR and BenM. Particularly, the difference between
      Thr33 in CbnR and Ser33 in BenM appears to affect the conformations of
      neighboring residues, leading to the selective interactions with DNA. DATABASE:
      Atomic coordinates and structure factors for the DNA-binding domain of
      Cupriavidus necatorNH9 CbnR in complex with RBS are available in the Protein Data
      Bank under the accession code 5XXP.

PMID- 29323786
TI  - Pulmonary endoplasmic reticulum stress-scars, smoke, and suffocation.
AB  - Protein misfolding within the endoplasmic reticulum (ER stress) can be a cause or
      consequence of pulmonary disease. Mutation of proteins restricted to the alveolar
      type II pneumocyte can lead to inherited forms of pulmonary fibrosis, but even
      sporadic cases of pulmonary fibrosis appear to be strongly associated with
      activation of the unfolded protein response and/or the integrated stress
      response. Inhalation of smoke can impair protein folding and may be an important
      cause of pulmonary ER stress. Similarly, tissue hypoxia can lead to impaired
      protein homeostasis (proteostasis). But the mechanisms linking smoke and hypoxia
      to ER stress are only partially understood. In this review, we will examine the
      role of ER stress in the pathogenesis of lung disease by focusing on fibrosis,
      smoke, and hypoxia.

PMID- 29323787
TI  - Inhibition of UVSSA ubiquitination suppresses transcription-coupled nucleotide
      excision repair deficiency caused by dissociation from USP7.
AB  - Transcription-coupled nucleotide excision repair (TC-NER) is a subpathway of
      nucleotide excision repair that efficiently removes transcription-blocking DNA
      damage from the transcribed strands of active genes. UVSSA is a causative gene
      for UV-sensitive syndrome (UVS S), which is an autosomal recessive disorder
      characterized by hypersensitivity to UV light and deficiency in TC-NER. UV
      stimulated scaffold protein A (UVSSA), the product of UVSSA, forms a complex with
      ubiquitin-specific peptidase 7 (USP7) and is stabilized by interaction with USP7.
      The central region of UVSSA, which contains the tumor necrosis factor receptor
      associated factor (TRAF)-binding motif, is required for the interaction with the
      N-terminal TRAF domain of USP7. Here, we showed that UVSSA is mono-ubiquitinated
      in vitro and identified a lysine residue (Lys414 ) in UVSSA as the target of
      ubiquitination. The deubiquitination activity of USP7 was inhibited by the
      ubiquitin-conjugating enzyme UbcH6. Lys414 was also modified by poly-ubiquitin
      chains in vivo. UVSSA deficient in the interaction with USP7 is ubiquitinated and
      degraded by the proteasome, and the degradation leads to deficiency in TC-NER.
      The substitution of Lys414 by Arg of UVSSA inhibited its degradation and thereby
      suppressed the deficiency in TC-NER.

PMID- 29323788
TI  - Constructing Ordered Three-Dimensional TiO2 Channels for Enhanced Visible-Light
      Photocatalytic Performance in CO2 Conversion Induced by Au Nanoparticles.
AB  - As a typical photocatalyst for CO2 reduction, practical applications of TiO2
      still suffer from low photocatalytic efficiency and limited visible-light
      absorption. Herein, a novel Au-nanoparticle (NP)-decorated ordered mesoporous
      TiO2 (OMT) composite (OMT-Au) was successfully fabricated, in which Au NPs were
      uniformly dispersed on the OMT. Due to the surface plasmon resonance (SPR) effect
      derived from the excited Au NPs, the TiO2 shows high photocatalytic performance
      for CO2 reduction under visible light. The ordered mesoporous TiO2 exhibits
      superior material and structure, with a high surface area that offers more
      catalytically active sites. More importantly, the three-dimensional transport
      channels ensure the smooth flow of gas molecules, highly efficient CO2
      adsorption, and the fast and steady transmission of hot electrons excited from
      the Au NPs, which lead to a further improvement in the photocatalytic
      performance. These results highlight the possibility of improving the
      photocatalysis for CO2 reduction under visible light by constructing OMT-based Au
      SPR-induced photocatalysts.

PMID- 29323789
TI  - Mucosal ischaemia and bowel gangrene can have different treatment options in
      sigmoid volvulus.

PMID- 29323790
TI  - RNA-Templated Concatenation of Triplet Nucleic-Acid Probe.
AB  - Template-directed synthesis offers several distinct benefits over conventional
      laboratory creation, including unsurpassed reaction rate and selectivity.
      Although it is central to many biological processes, such an approach has rarely
      been applied to the in situ synthesis and recognition of biomedically relevant
      target. Towards this goal, we report the development of a three-codon nucleic
      acid probe containing a C-terminal thioester group and an N-terminal cysteine
      that is capable of undergoing template-directed oligomerization in the presence
      of an RNA target and self-deactivation in its absence. The work has implications
      for the development of millamolecular nucleic-acid probes for targeting RNA
      repeated expansions associated with myotonic dystrophy type 1 and other related
      neuromuscular and neurodegenerative disorders.

PMID- 29323791
TI  - Imine-Based Architectures at Surfaces and Interfaces: From Self-Assembly to
      Dynamic Covalent Chemistry in 2D.
AB  - Within the last two decades, dynamic covalent chemistry (DCC) has emerged as an
      efficient and versatile strategy for the design and synthesis of complex
      molecular systems in solution. While early examples of supramolecularly assisted
      covalent synthesis at surfaces relied strongly on kinetically controlled
      reactions for post-assembly covalent modification, the DCC method takes advantage
      of the reversible nature of bond formation and allows the generation of the new
      covalently bonded structures under thermodynamic control. These structurally
      complex architectures obtained by means of DCC protocols offer a wealth of
      solutions and opportunities in the generation of new complex materials that
      possess sophisticated properties. In this focus review we examine the formation
      of covalently bonded imine-based discrete nanostructures as well as one
      dimensional (1D) polymers and two-dimensional (2D) covalent organic frameworks
      (COFs) physisorbed on solid substrates under various experimental conditions, for
      example, under ultra-high vacuum (UHV) or at the solid-liquid interface. Scanning
      tunneling microscopy (STM) was used to gain insight, with a sub-nanometer
      resolution, into the structure and properties of those complex nanopatterns.

PMID- 29323792
TI  - The retinamide VNLG-152 inhibits f-AR/AR-V7 and MNK-eIF4E signaling pathways to
      suppress EMT and castration-resistant prostate cancer xenograft growth.
AB  - VNLG-152 is a novel retinamide (NR) shown to suppress growth and progression of
      genetically diverse prostate cancer cells via inhibition of androgen receptor
      signaling and eukaryotic initiation factor 4E (eIF4E) translational machinery.
      Herein, we report therapeutic effects of VNLG-152 on castration-resistant
      prostate cancer (CRPC) growth and metastatic phenotype in a CRPC tumor xenograft
      model. Administration of VNLG-152 significantly and dose-dependently suppressed
      the growth of aggressive CWR22Rv1 tumors by 63.4% and 76.3% at 10 and 20 mg.kg-1
      bw, respectively (P < 0.0001), vs. vehicle with no host toxicity. Strikingly, the
      expression of full-length androgen receptor (f-AR)/androgen receptor splice
      variant-7 (AR-V7), mitogen-activated protein kinase-interacting kinases 1 and 2
      (MNK1/2), phosphorylated eIF4E and their associated target proteins, including
      prostate-specific antigen, cyclin D1 and Bcl-2, were strongly decreased in VNLG
      152-treated tumors signifying inhibition of f-AR/AR-V7 and MNK-eIF4E signaling in
      VNLG-152-treated CWR22Rv1 tumors as observed in vitro. VNLG-152 also suppressed
      the epithelial to mesenchymal transition in CWR22Rv1 tumors as evidenced by
      repression of N-cadherin, beta-catenin, claudin, Slug, Snail, Twist, vimentin and
      matrix metalloproteinases (MMP-2 and MMP-9) with upsurge in E-cadherin. These
      results highlight the promising use of VNLG-152 in CRPC therapy and justify its
      further development towards clinical trials.

PMID- 29323793
TI  - Atmospheric nitrogen deposition on petals enhances seed quality of the forest
      herb Anemone nemorosa.
AB  - Elevated atmospheric input of nitrogen (N) is currently affecting plant
      biodiversity and ecosystem functioning. The growth and survival of numerous plant
      species is known to respond strongly to N fertilisation. Yet, few studies have
      assessed the effects of N deposition on seed quality and reproductive
      performance, which is an important life-history stage of plants. Here we address
      this knowledge gap by assessing the effects of atmospheric N deposition on seed
      quality of the ancient forest herb Anemone nemorosa using two complementary
      approaches. By taking advantage of the wide spatiotemporal variation in N
      deposition rates in pan-European temperate and boreal forests over 2 years, we
      detected positive effects of N deposition on the N concentration (percentage N
      per unit seed mass, increased from 2.8% to 4.1%) and N content (total N mass per
      seed more than doubled) of A. nemorosa seeds. In a complementary experiment, we
      applied ammonium nitrate to aboveground plant tissues and the soil surface to
      determine whether dissolved N sources in precipitation could be incorporated into
      seeds. Although the addition of N to leaves and the soil surface had no effect, a
      concentrated N solution applied to petals during anthesis resulted in increased
      seed mass, seed N concentration and N content. Our results demonstrate that N
      deposition on the petals enhances bioaccumulation of N in the seeds of A.
      nemorosa. Enhanced atmospheric inputs of N can thus not only affect growth and
      population dynamics via root or canopy uptake, but can also influence seed
      quality and reproduction via intake through the inflorescences.

PMID- 29323794
TI  - Skills transfer to sinus surgery via a low-cost simulation-based curriculum.
AB  - BACKGROUND: Surgical skill development outside the operating room aims to improve
      technique and subsequent patient safety. The purpose of this study was to
      evaluate the correlation between technical and cognitive skills with cadaveric
      endoscopic sinus surgery (ESS) performance and change in ESS performance before
      and after implementation of a dedicated ESS simulation-based and knowledge-based
      curriculum. METHODS: A before-after study design was implemented among 10 medical
      students and 10 junior otolaryngology residents. Participants completed a
      knowledge-based, multiple-choice ESS pretest and watched an ESS prosection video.
      Participants performed 9 tasks on a previously validated low-cost, low
      technology, nonbiologic sinus surgery task trainer followed by cadaveric
      maxillary antrostomy and anterior ethmoidectomy. Participants then completed a
      simulation-based and knowledge-based ESS curriculum followed by a repeat
      cadaveric maxillary antrostomy and anterior ethmoidectomy. Performance was graded
      with a 5-point global rating scale (GRS) and a 5-point ESS-specific checklist.
      RESULTS: We observed a stronger correlation between the multiple-choice,
      knowledge-based, ESS pretest scores and cadaveric ESS GRS score (r = 0.73) than
      between task trainer performance and cadaveric ESS GRS score (r = 0.43). We also
      noted a significant increase in precurriculum vs postcurriculum mean +/- standard
      deviation (SD) cadaveric ESS checklist scores for both medical students (1.18 +/-
      0.25 vs 2.58 +/- 0.57; p = 0.0002) and residents (2.09 +/- 0.78 vs 2.88 +/- 0.54;
      p = 0.023). The greatest improvements for residents were in performance of
      uncinectomy, enlargement of maxillary os, and identification of the bulla.
      CONCLUSION: These findings provide evidence supporting the use of ESS training
      curricula outside the operating room.

PMID- 29323795
TI  - A Pharmacokinetic Study of an Ibuprofen Topical Patch in Healthy Male and Female
      Adult Volunteers.
AB  - The pharmacokinetics of a novel locally applied ibuprofen topical patch was
      evaluated. Healthy subjects (n = 28) were administered a 200-mg ibuprofen patch
      every 24 hours for 5 days, and steady-state pharmacokinetics was determined. The
      amount of ibuprofen remaining in the patch following each patch removal was also
      assessed. The maximum steady-state drug concentration and area under the
      concentration curve from time 0 on day 5 (t = 0) to the 24-hours sample on day 6
      were 514 ng/mL (95% CI 439 to 603 ng/mL) and 9.78 kg.h/mL (95% CI 8.43 to 11.4
      kg.h/mL), respectively. Maximum ibuprofen concentration on day 5 occurred at 20
      hours post-patch application. No evidence of drug accumulation was observed, and
      steady state was achieved between days 2 and 5. Ibuprofen levels attenuated
      rapidly to baseline within 24 hours after treatment discontinuation. The amount
      of ibuprofen remaining in the patch was high (>=80%). Treatment-emergent adverse
      events were generally mild, with the most prevalent being headache (n = 6;
      21.4%). Only 4 TEAEs were considered related to the ibuprofen patch: paresthesia
      (n = 1), headache (n = 2), and pruritic rash (n = 1). The study found that the
      systematic absorption of ibuprofen from a 200-mg patch was low and that the
      levels of ibuprofen leaving the patch over a 24-hour period are consistent with
      levels required for therapeutic relief as shown in other studies.

PMID- 29323796
TI  - Treatment of chronic rhinosinusitis with dornase alfa in patients with cystic
      fibrosis: a systematic review.
AB  - BACKGROUND: A major component of sputum in cystic fibrosis (CF) patients is
      polymerized DNA, a byproduct of degraded neutrophils. Dornase alfa (dornase)
      selectively cleaves extracellular DNA and reduces the viscosity of sputum. It
      improves mucociliary clearance and pulmonary function. The benefit of dornase on
      CF-associated sinusitis is less clear. Therefore, the objective of this study was
      to systematically review the use of dornase on chronic rhinosinusitis (CRS) in CF
      patients. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta
      Analyses statement was followed for this systematic review. Ovid Medline, EMBASE,
      PubMed, and the Cochrane Library were searched. The search terms "dornase alfa,"
      "deoxyribonucleases," "rhinosinusitis," and "cystic fibrosis" were used to find
      articles published between 1990 and 2016. The articles were reviewed for study
      design, level of evidence, and clinical outcomes. RESULTS: Sixty-two articles
      were identified; 6 met the inclusion criteria (104 patients). Improvement
      measured by sinonasal symptoms, endoscopic and radiographic findings, and
      pulmonary function was variably reported between the studies. Sinonasal symptoms
      were shown to improve in all studies with use of intranasal topical dornase.
      Three placebo-controlled studies showed that topical dornase significantly
      improved sinonasal symptoms more than saline alone. The impact on pulmonary
      function and radiographic and endoscopy findings was variable. CONCLUSION:
      Topical intranasal dornase appears to improve sinonasal symptoms in CF patients
      to a greater degree than saline alone. The impact on other outcomes is less
      clear. Larger studies are needed to fully elucidate the true efficacy of dornase
      alfa in the treatment of CRS in CF patients.

PMID- 29323798
TI  - Regarding Nursing Languages: Moving Beyond How We Feel.

PMID- 29323799
TI  - Knowledge, Perception, and Utilization of Standardized Nursing Language (SNL)
      (NNN) among Nurses in Three Selected Hospitals in Ondo State, Nigeria.
AB  - The use of standardized nursing languages helps nurses understand patients' needs
      with precision and speed. This study assessed the knowledge of standardized
      nursing languages (SNL); how nurses perceive SNL and nurses utilization of SNL.
      The study adopted a cross sectional research design. Participants were recruited
      using convenience sampling technique. Data was collected using 5-sectioned self
      structured questionnaires whose validity and reliability had been previously
      ascertained. Data collected was analyzed using Statistical Package for Social
      Sciences (SPSS) version 20. Results showed that majority of the nurses that
      participated in the study are female (83.8%). Only 60.0% of the nurses know the
      number of steps in nursing process while very few (5.4%) can correctly define
      what SNLs is. Knowledge of SNLs shows that 26.2% have high knowledge; 44.6%
      moderate knowledge while 29.2% had low knowledge. Utilization of SNL by nurses
      showed that Majority (83.8%) of the nurses in the study agreed that utilization
      of SNL help nurses to deliver quality nursing care; 67.7% of nurses agreed that
      the use of SNL makes nursing practice unique, 55.4% opined that the use of SNL
      can be cumbersome while only 24.6% often use nursing process for patients' care.
      Although, participants in this study agreed that the use of SNL is crucial to
      quality nursing care, with poor utilization.

PMID- 29323800
TI  - Erratum.

PMID- 29323803
TI  - Climate Change and Agriculture: Future Implications.

PMID- 29323804
TI  - The Changing Face of Hospital Medicine.

PMID- 29323805
TI  - Wisconsin Firearm Mortality, 2000-2014.
AB  - BACKGROUND: Despite low firearm mortality rates in Wisconsin, overall firearm
      fatalities continue to rise in recent years. In 2013, the statewide age-adjusted
      death rate due to firearms was 9.6 per 100,000 persons, the highest mark since
      the new millennium. This raises not only public safety concerns, but also raises
      questions regarding ongoing gun violence. OBJECTIVES: To describe the population
      and geographic characteristics of firearm mortality rates on population and
      geographic characteristics in Wisconsin. METHODS: Mortality data for firearm
      deaths caused by suicides, homicides and other death intent were obtained from
      the Wisconsin Interactive Statistics on Health (WISH) query system from 2000
      through 2014. The probability of firearm fatality was analyzed through log-linear
      Poisson regression models to assess the variations of firearm mortality risks in
      relation to a person's sex, age, race/ethnicity, and region. RESULTS: Firearm
      violence is responsible for 14% of injury-related deaths in Wisconsin. Seventy
      two percent of firearm-related deaths were attributed to suicides; the majority
      of decedents were white men aged 45 years or older. The proportion of homicides
      by gun to all homicides increased from 63% in 2000 to 72% in 2014.
      Disproportionally high firearm homicides were found among black men aged 18 to 34
      years in southeastern Wisconsin, accounting for 38% of the entire gun-related
      murder deaths. CONCLUSION: Our study shows that the association of the
      demographic and geographic characteristics with mortality rates differs among
      suicides, homicides and the other intent. Understanding characteristics
      associated with firearm related-deaths is the first step toward addressing them.

PMID- 29323806
TI  - Spine and Spinal Cord Injuries After Falls From Tree Stands During the Wisconsin
      Deer Hunting Season.
AB  - BACKGROUND: Deer hunting is popular in much of the United States. In Wisconsin,
      use of tree stands for hunting is common. Spine surgeons at a Level 1 Trauma
      Center observed a high incidence of spine and spinal cord injury due to falls
      from tree stands while hunting. This study's purpose is to systematically
      characterize and classify those injuries. METHODS: We reviewed the University of
      Wisconsin Hospital and Clinics' trauma database for tree stand-related injuries
      from 1999 to 2013. We collected and analyzed data pertaining to hunters'
      demographics, comorbidities, type and mechanism of injury, injury severity, and
      management. RESULTS: We identified 117 patients evaluated after a tree stand
      fall. Sixty-five (ages 16-76) suffered spine fractures that occurred at all
      levels, from occipital condyle to sacrum, with thoracolumbar compression and
      burst fractures being most common. Fractures occurred in the following locations:
      cranio-cervical junction (8.7%), cervical spine (7.6%), cervical-thoracic
      junction (6.5%), thoracic spine (32.6%), thoracolumbar junction (33.7%), and
      lumbar spine (10.9%). Twenty-one patients (32%) experienced a single spinal
      fracture; 44 patients (68%) suffered multiple spinal fractures. Twenty-five
      patients (38%) required surgical fixation; 19 patients experienced loss of
      neurologic function: 5 complete spinal cord injuries (SCI), 5 incomplete SCI, 2
      central cord syndromes, and 8 radiculopathies. Two mortalities, both of
      cardiopulmonary etiology, were noted-one in a patient without a spine fracture
      and the other in a patient with a complete spinal cord injury at T4. CONCLUSIONS:
      The majority of spine fractures are treated nonoperatively. However, enough
      patients require surgical intervention that consultation with a neurosurgical or
      orthopedic spine surgeon is prudent. It is more common to have multiple spine
      fractures from a tree stand fall, therefore, it is recommended that if 1 fracture
      is identified the entire spine be evaluated for additional fractures. For safety,
      it is recommended that hunters wear and use safety harnesses appropriately.
      Additionally, keeping the height of the tree stand at 10 feet or less is
      associated with a lower likelihood of spinal cord injury. Further study is needed
      to determine additional interventions such as education that might reduce the
      injury frequency in this population.

PMID- 29323807
TI  - Impact of Obesity on Cesarean Delivery Outcomes.
AB  - BACKGROUND: The rate of cesarean delivery has increased over the last 2 decades.
      Obesity is a risk factor for complications during pregnancy and cesarean
      procedures. The objective of this study was to evaluate cesarean delivery
      outcomes in patients with vs without obesity, and determine the impact of obesity
      on complications. METHODS: The medical records of patients who underwent a
      cesarean delivery from 2010 to 2014 were reviewed. Patients were grouped by body
      mass index (BMI) into obese (>=30kg/m2) and non-obese (<30kg/m2) cohorts for
      comparison. RESULTS: Nine hundred seventy-one patients were included; 432 whom
      had obesity, and 539 did not have obesity. The rate of gestational diabetes was
      increased among patients with vs without obesity (15.3% vs 5.8%; P<0.001).
      Obesity was associated with an increased incidence of surgical site infections
      (8.1% vs 2.4%; P<0.001), yeast infection (2.8% vs 0.2%; P<0.001), and seroma
      (2.8% vs 0.4%; P=0.002). Obesity was an independent risk factor for surgical site
      infections, regardless of wound closure technique (adjusted odds ratio=3.24, 95%
      CI, 1.66-6.32; P<0.001). CONCLUSIONS: Obesity is a risk factor for wound
      infections after a cesarean delivery. As obesity rates increase, it is important
      to be aware of these risks after performing a cesarean delivery.

PMID- 29323797
TI  - Relations between cortical thickness, serotonin 1A receptor binding, and
      structural connectivity: A multimodal imaging study.
AB  - Serotonin 1A (5-HT1A ) receptors play a direct role in neuronal development, cell
      proliferation, and dendritic branching. We hypothesized that variability in 5
      HT1A binding can affect cortical thickness, and may account for a subtype of
      major depressive disorder (MDD) in which both are altered. To evaluate this, we
      measured cortical thickness from structural magnetic resonance imaging (MRI) and
      5-HT1A binding by positron emission tomography (PET) in an exploratory study. To
      examine a range of 5-HT1A binding and cortical thickness values, we recruited 25
      healthy controls and 19 patients with MDD. We hypothesized increased 5-HT1A
      binding in the raphe nucleus (RN) would be negatively associated with cortical
      thickness due to reduced serotonergic transmission. Contrary to our hypothesis,
      raphe 5-HT1A binding was positively correlated with cortical thickness in right
      posterior cingulate cortex (PCC), a region implicated in the default mode
      network. Cortical thickness was also positively correlated with 5-HT1A in each
      cortical region. We further hypothesized that the strength of 5-HT1A -cortical
      thickness correlation depends on the number of axons between the raphe nucleus
      and each region. To explore this we related 5-HT1A -cortical thickness
      correlation coefficients to the number of tracts connecting that region and the
      raphe, as measured by diffusion tensor imaging (DTI) in an independent sample.
      The 5-HT1A -cortical thickness association correlated significantly with the
      number of tracts to each region, supporting our hypothesis. We posit a defect in
      the raphe may affect the PCC within the default mode network in MDD through
      serotonergic fibers, resulting in increased ruminative processing.

PMID- 29323808
TI  - Adolescent Preferences for Topics Addressed During Well Visits.
AB  - BACKGROUND: Current evidence is limited regarding the topics adolescents want to
      discuss with clinicians during routine well visits. High school students were
      surveyed to determine potential adolescent discussion topics, barriers to
      discussion, and ways to promote dialogue. METHODS: Surveys were distributed
      between October 2014 and January 2015 to 102 students in the Verona Area High
      School in Verona, Wisconsin. RESULTS: Of the topics presented, teens preferred to
      discuss vaccines and mood/stress with their clinicians. Young women were more
      likely to prefer gender congruent clinicians, especially when discussing sex or
      body image. The majority of teens felt that information discussed with their
      physician would be revealed to parents or the authorities. CONCLUSIONS: In
      limited time with teens, it is important for clinicians to reinforce
      confidentiality to gain their trust. Clinicians can improve rapport with
      adolescents by revealing information about themselves, conveying genuine caring,
      and considering community involvement. Male clinicians need to work on improving
      rapport, especially when talking with female adolescents about sex, body image,
      stress, and mood. Clinicians should consider including mood, stress, and vaccine
      discussions in their adolescent well visits.

PMID- 29323809
TI  - Case Report of an Ectopic Molar Pregnancy in the Presence of an Intrauterine
      Device.
AB  - BACKGROUND: Ectopic molar pregnancy is a rare phenomenon and has not been
      reported in the presence of an intrauterine device (IUD). Clinical diagnosis of
      molar pregnancy is challenging and requires careful follow-up. CASE: A 25-year
      old woman (gravida 2, para 0) with a copper IUD in place presented with a
      positive pregnancy test. Diagnosis of the complete hydatidiform mole was
      pathologically confirmed after surgery following clinical and sonographic
      investigations that identified a left-sided ectopic pregnancy. CONCLUSION:
      Gestational trophoblastic disease (GTD) presenting as an ectopic pregnancy is a
      very rare occurrence. This patient recovered without event through a combined
      management and follow-up for ectopic pregnancy and gestational trophoblastic
      disease. Appropriate identification and management of this clinical problem is
      essential in order to prevent initial complications as well as subsequent
      malignant sequelae.

PMID- 29323810
TI  - Hospital Medicine and Fellowship Program in Rural North Dakota - A Multifaceted
      Success Story.
AB  - INTRODUCTION: Recruitment of hospitalists and primary care physicians for
      Critical Access Hospitals and tertiary care hospitals in North Dakota is
      difficult. To address this challenge, 2 programs were implemented in Bismarck,
      North Dakota. METHODS: St. Alexius Medical Center created a hospitalist
      fellowship training program in collaboration with the University of North Dakota
      School of Medicine and Health Sciences and physicians willing to work in Critical
      Access Hospitals were offered a joint appointment to teach hospitalist fellows
      and obtain a clinical academic appointment at the university. RESULTS: Since it
      was created in 2012, 84 physicians have applied for 13 fellowships. Of the 11
      fellows who have completed the program, 64% (7/11) remained in North Dakota to
      practice. CONCLUSIONS: Physicians are more likely to work in a rural Critical
      Access Hospital if they spend time working at a tertiary care center and have
      clinical academic appointments. Where recruitment is challenging, hospitalist
      fellowship programs are helpful in meeting the health care workforce demand.

PMID- 29323811
TI  - 'Are You the Man?' and 'Patriotism'.

PMID- 29323812
TI  - The United States' Research Enterprise.

PMID- 29323813
TI  - Antibiotic Stewardship in the Outpatient Setting.

PMID- 29323814
TI  - Physician Advocacy is ProAssurance's Specialty.

PMID- 29323815
TI  - How Physicians Can Save 56 Hours Per Year.

PMID- 29323816
TI  - An Epidemic, a Scourge, or a Plague.

PMID- 29323817
TI  - The National Opioid Epidemic: Local, State, and National Responses.

PMID- 29323818
TI  - Opioid Use for Treatment of Chronic Pain: An Overview and Treatment Guideline for
      Injured Workers Responses.

PMID- 29323819
TI  - The Use of a Statewide Prescription Drug Monitoring Program by Emergency
      Department Physicians.
AB  - BACKGROUND: Little is known about how emergency physicians have used Wisconsin's
      Prescription Drug Monitoring Program (PDMP). OBJECTIVE: To characterize emergency
      physician knowledge and utilization of the program and how it modifies practice.
      METHODS: Online survey data were collected 1 year after program implementation.
      Descriptive statistics were generated and qualitative responses were grouped by
      content. RESULTS: Of the 63 respondents, 64.1% had used the program. Lack of a
      DEA number and knowledge about how to sign up were the most common barriers to
      registration. Over 97% of program users found it useful for confirming suspicion
      of drug abuse and 90% wrote fewer prescriptions after program implementation.
      Time constraints and the difficult log-in process were common barriers to use.
      More users than nonusers stated that their workplace was supportive of program
      use. CONCLUSIONS: Although barriers exist, PDMP utilization appears useful to
      emergency physicians and associated with modifications to patient management.

PMID- 29323820
TI  - Genetics and Genomics in Clinical Practice: The Views of Wisconsin Physicians.
AB  - INTRODUCTION: Decreasing costs and increased availability of genetic testing and
      genome sequencing mean many physicians will consider using these services over
      the next few years. Despite this promising future, some argue the present roadmap
      for translating genetics and genomics into routine clinical practice is unclear.
      OBJECTIVE: We conducted a pilot study to explore Wisconsin physicians' views,
      practices and educational desires regarding genetic and genomic testing. METHODS:
      Our study consists of an Internet survey (n=155) conducted in August and
      September 2015 and follow-up phone interviews with a portion of survey
      participants. Physicians of all specialties were invited to participate.
      Variables measured include physicians' general knowledge and experience regarding
      genetic and genomic testing, attitudes and perceptions toward these tests,
      testing intentions, and educational desires. Sociodemographic variables included
      gender, age, and medical specialty. RESULTS: In our exploratory survey of
      Wisconsin physicians, adult primary care providers (PCPs) lagged behind other
      providers in terms of familiarity and experience with genetic and genomic
      testing. PCPs in our sample were less likely than other physicians to feel their
      training in genetics and genomics is adequate. Physicians younger than 50 were
      more likely than older colleagues to feel their training is adequate.
      CONCLUSIONS: Our exploratory study suggests a gap in physician education and
      understanding regarding genomic testing, which is fast becoming part of
      personalized medical care. Future studies with larger samples should examine ways
      for physicians to close this gap, with special focus on the needs of PCPs.

PMID- 29323822
TI  - Hand Hygiene Among Health Care Workers: Is Educating Patients and Families a
      Feasible Way to Increase Rates?
AB  - BACKGROUND: The Centers for Disease Control and Prevention has recommended
      teaching patients to remind health care workers to disinfect their hands.
      However, cognitive impairment among patients may hamper such efforts. METHODS:
      The St. Louis University Mental Status (SLUMS) Examination was administered to
      randomly selected inpatients at the Omaha VA Medical Center in Omaha, Nebraska.
      We asked patients and their families about attitudes toward reminding health care
      workers to disinfect their hands: willingness, feeling comfortable, and feeling
      responsible. RESULTS: Of 143 patients, 94 completed SLUMS; 9 had normal mental
      status and appropriate attitudes. Overall, 16 encounters involved patients or
      family who were well-suited for giving reminders. CONCLUSION: Programs to
      encourage hospitalized adults to remind staff to perform hand hygiene may
      encounter barriers related to cognitive impairment and attitudes.

PMID- 29323821
TI  - Implementing Population Medicine in a Pain Management Practice.
AB  - PURPOSE: To document and improve the quality of our chronic pain management using
      population management methods. METHODS: An analytic registry was developed, and
      all new patients were enrolled for 12 months. Patient demographics, standardized
      pain and function measures, and treatments were recorded. Usual care was
      provided. The registry was used to organize care and analyze management and
      outcomes. RESULTS: Of 454 total patients, only 154 (34%) completed a 6-month
      cycle of care. High no-show rates were documented for follow-up appointments for
      several reasons. The majority of 6-month completers showed improved pain levels.
      DISCUSSION: This quality improvement project identified assessment and care gaps
      and led to improvements. An ongoing need to improve measures of pain and function
      was documented.

PMID- 29323823
TI  - Atrioesophageal Fistula: A Rare Complication of Radiofrequency Ablation.
AB  - 75-year-old woman was admitted with fever, chills, altered mentation, and right
      sided weakness. A month earlier, she had undergone catheter radiofrequency
      ablation for treatment of chronic atrial fibrillation. A magnetic resonance
      imaging scan of her brain revealed septic emboli with multiple bilateral cerebral
      and cerebellar infarcts, as well as extensive bilateral leptomeningeal
      enhancement. Blood cultures were positive for Streptococcus mitis, Rothia
      mucilaginosa, Streptococcus pneumonia, and Candida albicans, which suggested a
      connection between gastrointestinal and cardiovascular systems. A chest computed
      tomography scan with contrast showed a curvilinear low attenuation structure
      communicating between the esophagus and the left pulmonary vein-an
      atrioesophageal fistula. Ten days after admission, the patient died from multiple
      cerebral septic emboli secondary to atrioesophageal fistula following
      radiofrequency ablation.

PMID- 29323824
TI  - A Case of Atypical Synovitis-Acne-Pustulosis-Hyperostosis-Osteitis (SAPHO)
      Syndrome Presenting With Osteomyelitis of the Clavicle.
AB  - Synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO) syndrome is considered
      after exclusion of infection and arthritis; however, microbial infection may be
      present in osteoarticular lesions of these patients. Chronic osteomyelitis and
      associated bacterial infection were detected in a recurrent osteoarticular lesion
      in an adolescent patient with a history of clavicle pain, who complained of
      recurrent swelling in the left clavicle. Most pediatric case reports of SAPHO
      syndrome describe patients with associated skin conditions. This case report
      describes a patient diagnosed with SAPHO syndrome with no associated skin
      condition. Although SAPHO syndrome is characterized by dermatological and
      osteological symptoms, this acronym describes a collection of recurring symptoms.
      Complete patient medical history and thorough testing, including radiology and
      biopsy, are critical for prompt diagnosis and treatment of this condition,
      particularly in pediatric patients with persistent skeletal pain.

PMID- 29323826
TI  - Transforming Medical Education.

PMID- 29323825
TI  - Working to Address the Opioid Crisis.

PMID- 29323827
TI  - Understanding the Medicare Quality Payment Program.

PMID- 29323828
TI  - The Problem With US Health Care: It Ain't Obamacare!

PMID- 29323829
TI  - Working With Communities Toward Health Equity.

PMID- 29323830
TI  - The Vision Spirit.

PMID- 29323832
TI  - Influences of a Church-Based Intervention on Falls Risk Among Seniors.
AB  - BACKGROUND AND OBJECTIVES: Prior studies illustrate that community-based programs
      effectively decrease falls risk in older adults and that faith-based programs
      improve health behaviors. The literature is unclear whether faith-based
      initiatives reduce seniors' fall risks. To tackle this gap, a long-term
      partnership led by 10 urban churches, a nearby nursing school, and a medical
      school developed a study with 3 objectives: determine baseline health concerns
      associated with falls (eg, depression, polypharmacy), implement a nurse-led,
      faith-based health education initiative for community-dwelling African American
      seniors at-risk of hospitalization, and assess pre- to post -program fall
      frequency. METHODS: The 100 Healthy, At-Risk Families study team implemented 8
      monthly educational health sessions promoting self-care and social support.
      Community nurses led the 60- to 90-minute sessions at each of 10 churches. To
      collect study data, nurses interviewed enrolled seniors pre- and post
      intervention. Descriptive and comparison statistics were analyzed in Excel and
      Statistical Package for Social Sciences. RESULTS: Senior data at baseline found
      high rates of polypharmacy and physical imbalance, and no significant depression
      or gaps in social support. There was not a statistically significant change pre-
      to post-program in fall frequency "in prior year." CONCLUSIONS: Study findings
      reveal insights about African American senior health and fall risks. Church
      settings may provide a protective, psychosocial buffer for seniors, while
      polypharmacy and mobility/balance concerns indicate need for continued attention
      to fall risks. No increase in pre- to post-program falls was encouraging.

PMID- 29323833
TI  - Wheels For All: Addressing Social Determinants of Health One Bicycle at a Time.
AB  - BACKGROUND: Wheels For All provides bicycles to individuals in La Crosse,
      Wisconsin to address the transportation barrier that often inhibits low-income
      individuals' ability to access community resources. METHODS: Recipients are
      referred by social service, health care, or other community agencies based on
      their need for transportation or exercise. Donated bicycles are matched to a
      recipient, repaired, and delivered personally by volunteers. RESULTS: Through
      collaboration with social service agencies, health care systems, and the
      community at-large, Wheels For All received referrals from 21 different sources
      and provided 101 recipients with bicycles from April 2015 to July 2017.
      CONCLUSION: Using a cost-effective, community-engagement model, Wheels For All
      provides a means of transportation for recipients, resulting in an enhanced
      ability to access community resources.

PMID- 29323831
TI  - Biking for Health: Results of a Pilot Randomized Controlled Trial Examining the
      Impact of a Bicycling Intervention on Lower-Income Adults.
AB  - INTRODUCTION: This pilot study tested the efficacy of a bicycling intervention
      targeting inactive, low-income, overweight adults on reducing perceived barriers
      to bicycling, increasing physical activity, and improving health. METHODS: A
      nonblinded 2-site randomized controlled trial was conducted in Milwaukee,
      Wisconsin, in summer 2015. Participants included members from 1 largely Latino
      community and a second primarily African American neighborhood. A certified
      bicycling instructor led a 12-week bicycling intervention. Outcome measures
      including biking-related attitudes, self-reported physical activity, fitness as
      measured by the 6-minute step test, and biometric data were collected at
      baseline, 12 weeks, and 20 weeks. RESULTS: Thirty-eight participants completed
      the study. Barriers to bicycling declined significantly among intervention group
      participants at 12 weeks with some declines persisting to 20 weeks. Bicycling for
      leisure or non work transportation increased significantly more in the
      intervention than control group from baseline to 12 weeks but this difference
      attenuated by 20 weeks. Both groups increased their fitness between baseline and
      12 weeks, with a trend towards greater gains in the bicycling intervention group.
      No significant change in biometric measurements was seen at either 12 weeks or 20
      weeks. CONCLUSION: Despite the small study size, this bicycling intervention
      decreased perceived barriers to bicycling and increased bicycling activity in low
      income minority participants. These findings support a larger-scale study to
      measure fitness and health changes from bicycling interventions.

PMID- 29323834
TI  - !Venga Y Relajese! Pilot Stress Reduction Program for Migrant Latina Women Living
      in Low-Resource Settings From Milwaukee to Lima.
AB  - Latina women living in low-income communities frequently report a high prevalence
      of feeling physically and/or emotionally "unwell." Formative focus groups were
      used to design a 3-session stress reduction curriculum called !Venga y Relajese!
      (Come and relax yourself!). Survey data from 5 Milwaukee cohorts and 1 Peruvian
      cohort revealed statistically significant improvements in general health status,
      perceived stress status, and confidence to manage future stress among women who
      completed all sessions (n=54). The pilot !Venga y Relajese! stress reduction
      curriculum yielded benefits for Latina women living in low-income neighborhoods
      in Milwaukee, Wisconsin and Lima, Peru.

PMID- 29323835
TI  - Recurring Vivid Dreams in an Older Hmong Man With Complex Trauma Experience and
      Cognitive Impairment.
AB  - INTRODUCTION: Health care workers need to consider the culture and ethnic
      preferences prevalent in the Hmong community in order to provide optimal care. We
      describe an older Hmong man to illustrate the challenges faced and competencies
      needed by primary care. CASE PRESENTATION: An 80-year-old non-English speaking
      Hmong man with diabetes, nerve sheath tumor, and hypertension presented to the
      outpatient clinic with his grandson complaining of sleep problems. He had had 2
      vivid recurring dreams during the previous few months. Memory assessment was
      significant for dementia. DISCUSSION: This case addresses the complexity in
      taking care of a non-English speaking Hmong older man who has memory loss, trauma
      in adulthood, multiple caregivers, and sleep problems. CONCLUSIONS: A careful
      history from patient and family to get to know their cultural preferences and
      attitudes was helpful. Identification of the primary caregiver was critical in
      providing care.

PMID- 29323837
TI  - What Constitutes Prosperity.

PMID- 29323836
TI  - Segmental Arterial Mediolysis: An Unusual Case Mistaken to be a Strangulated
      Hernia.
AB  - INTRODUCTION: Segmental arterial mediolysis (SAM) is a rare nonatherosclerotic,
      noninflammatory vasculopathy causing arterial wall necrosis that leads to
      strictures, dissections, and aneurysms, particularly in medium-sized abdominal
      arteries. Awareness of SAM is important because, unlike vasculitides,
      immunosuppressive treatment may worsen the disease process. CASE: A 58-year-old
      man with multiple medical comorbidities presented with acute epigastric pain and
      a right incarcerated inguinal hernia that was interpreted as showing bowel
      strangulation on computed tomography. The hernia was unable to be reduced in the
      emergency department, so the patient was taken for open reduction by the surgical
      service. Intraoperatively, he was noted to have a ruptured superior mesenteric
      artery aneurysm. Conventional angiography demonstrated a bead-like appearance of
      several jejunal branches of the superior mesenteric artery, raising concern for a
      vasculitis. His hospital course included rheumatologic consultation, and initial
      recommendations were to start immunosuppressive therapy for treatment of
      polyarteritis nodosa. Further testing demonstrated normal antinuclear antibody,
      antineutrophil cytoplasmic antibodies, and complement levels. Due to a lack of
      systemic symptoms or signs and otherwise unremarkable laboratory evaluation, the
      patient ultimately was diagnosed with SAM and immunosuppressive therapy was
      halted. DISCUSSION: Unexplained medium arterial stenosis, dissection, aneurysm,
      and hemorrhage should raise suspicion for possible SAM. The initial management
      approach should focus on treatment of the acute hemorrhage, usually involving
      endovascular stenting or coil embolization. Unlike vasculitides, SAM does not
      benefit from, and may actually be harmed by, immunosuppressive therapy.
      CONCLUSIONS: Clinicians involved in the longitudinal care of emergency department
      patients should be aware of this rare clinical entity in order to initiate
      appropriate treatment.

PMID- 29323838
TI  - Embracing Innovation in Medical Education.

PMID- 29323839
TI  - Alcohol Use Increasing Among Adults 65 and Older.

PMID- 29323840
TI  - Phosphazide (nikavir) is a highly effective drug for the treatment of HIV/AIDS
      infection.
AB  - Federation Convincing evidence for high therapeutic activity and tolerability of
      Phosphazide in the treatment of HIV/AIDS-infection is given. Phosphazide is
      currently used in various regimens of highly active antiretroviral therapy, as
      well as in the HIV therapy in patients with simultaneously acquired chronic
      hepatitis C or tuberculosis. Therapeutic possibilities of Phosphazide were
      clearly manifested in the prevention of HIV transmission from mother to child.
      There is every reason to use Phosphazide in first-line antiretroviral therapy.

PMID- 29323841
TI  - Influenza A virus in the Western Arctic.
AB  - Small bays of bird bazaars of the Arctic Kola Peninsula (Barents Sea) have been
      studied. RNA of influenza A virus was found in the surface microlayer (SM) and
      aerosol samples from the bays located beneath bird colonies. The nucleotide
      sequencing of the PCR fragments from the SM and the sea aerosol showed their
      identity for each bay. Virus transfer mechanism along the "surface microlayer -
      sea aerosol" path has been proposed. The kinetic scheme of the virus-host
      environment interaction, which allows the dependence of the viral population size
      on the temperature to be simulated, has been developed.

PMID- 29323842
TI  - A new method of producing NS5A antigen of hepatitis C virus.
AB  - A task of creating a universal platform for engineering affordable recombinant
      producers of viral proteins conserving immunogenicity has not been solved yet.
      High toxicity of the viral proteins for the host cells, low yield and abnormal
      folding of the products often present severe obstacles to obtaining producers of
      the viral proteins. In this work, we report a new method of engineering and
      screening of deletion libraries from the viral antigen genes. This method allows
      selection of artificial derivatives of these genes adapted for expression in
      microbial producer cells. The method involves PCR amplification of the gene
      fragments using a system of randomized and adapter primers, which allows the
      spontaneous formation of duplexes from the random primers in the absence of the
      template DNA to be prevented. For selecting variants capable of in vivo
      expression, the obtained PCR products are cloned to a special vector of a direct
      phenotypical selection pQL30. It contains E. coli beta-galactosidase gene with an
      inserted polylinker producing a frame-shift mutation. Using this screening
      method, an artificial variant of hepatitis C (HCV) NS5a gene with optimal
      biotechnological properties was established. 27 clinical specimens of 1670 bp
      long HCV1b NS5a fragments were used as a source gene. A PCR bank of the deletion
      derivatives was produced. 40 LacZ-positive clones based on pQL30 vector with a 50
      700 bp long insertion were selected. The LacZ activity of the cell lysates and
      the immunogenicity of the products were tested. As a result, a single clone
      encoding a soluble protein with Mr = 114 kDa was selected. Its yield reached 0.3%
      of the total cell protein. It was highly reactive with sera of HCV 1b infected
      patients but not with sera of the healthy donors.

PMID- 29323843
TI  - An experience in the clinical use of specific immunoglobulin from horse blood
      serum for prophylaxis of Ebola haemorrhagic fever.
AB  - The aim of this work was to estimate the efficacy and safety of single
      intramuscular introduction of specific heterologous immunoglobulin as
      prophylactic drug against Ebola hemorrhagic fever. Materials and methods. The
      specific heterologous immunoglobulin was introduced as a special prophylactic
      drug to 28 patients in epidemic situations, after skin hurt with infectious
      materials or contact with infectious blood. Clinico-laboratory observation was
      performed in 24 subjects after single intramuscular introduction of heterologous
      immunoglobulin Ebola. The samples of blood serum were investigated for
      immunoglobulin Ebola and antibodies to horse gamma-globulin on the 30th and 60th
      days after prophylaxis. Results. None of the subjects of the study contracted
      Ebola fever. There were no anaphylactic reactions after special prophylaxis with
      specific heterologous immunoglobulin. Among the subjects with normal allergic
      state 31% responded with local reactions; 13%, with a general reaction (mild case
      of the serum disease). Almost no reaction was observed in patients with
      unfavorable allergic state subjected to desensitizing therapy; in the absence of
      desensitizing therapy, 50% of patients with unfavorable allergic state exhibited
      local reactions; 17%, mild cases of the serum disease; 33%, moderate cases of the
      serum disease. In summary, if the tactics of immunoglobulin application was
      right, the quantity of local allergic reactions was 28%; of wide spread
      reactions, 6%. Weak serum disease was observed in 11% of the subjects. The
      prognostic period of resistance to Ebola fever was less than 30 days. Conclusion.
      The prophylactic use of specific immunoglobulin from horse blood serum against
      hemorrhagic Ebola fever is effective and relatively safe in patients subjected to
      desensitizing therapy.

PMID- 29323844
TI  - Comparative analysis of genomes of tick-borne encephalitis virus strains isolated
      from mosquitoes and ticks.
AB  - The tick-borne encephalitis virus (TBEV) strain Lazo MP36 was isolated from the
      pool of mosquitoes Aedes vexans collected in Lazo region of Khabarovsk territory
      in August 2014. Phylogenetic analysis of the strain Lazo MP36 complete genome
      (GenBank accession number KT001073) revealed its correspondence to the TBEV Far
      Eastern subtype and differences from the following strains: 1) from ticks Ixodes
      persulcatus P. Schulze, 1930 [vaccine strain 205 (JX498939) and strains Khekhtzir
      1230 (KF880805), Chichagovka (KP844724), Birobidzhan 1354 (KF880805) isolated in
      2012-2013]; 2) from mosquitoes [strain Malyshevo (KJ744034) isolated in 1978 from
      Aedes vexans nipponii in Khabarovsk territory; strain Sakhalin 6-11 isolated from
      the pool of mosquitoes in 2011 (KF826916)]; 3) from human brain [vaccine strain
      Sofjin (JN229223), Glubinnoe/2004(DQ862460). Kavalerovo (DQ862460), Svetlogorie
      (DQ862460)]. The fusion peptide necessary for flavivirus entry to cells of the
      three TBEV strains isolated from mosquitoes (Lazo MP36, Malyshevo and Sakhalin 6
      11) has the canonical structure 98-DRGWGNHCGLFGKGSI-113 for the tick-borne
      flaviviruses. Amino acid transition H104G typical for the mosquito-borne
      flaviviruses was not found. Structures of 5'- and 3'-untranslated (UTR) regions
      of the TBEV strains from mosquitoes were 85-98% homologous to the TBEV strains of
      all subtypes without recombination with mosquito-borne flaviviruses found in the
      Far East of Russia. Secondary structures of 5'- and 3'-UTR as well as cyclization
      sequences (CS) of types a and B are highly homologous for all TBEV isolates
      independently of the biological hosts and vectors. similarity of the genomes of
      the TBEV isolates from mosquitoes, ticks and patients as well as pathogenicity of
      the isolates for new-borne laboratory mice and tissue cultures might suggest a
      possible role of mosquitoes in the TBEV circulation in natural foci as an
      accidental or additional virus carrier.

PMID- 29323845
TI  - Development of the suppository form of human immunoglobulin preparation with high
      titers of antibodies to herpes simplex virus types 1 and 2 for the treatment of
      chronic forms of herpetic disease.
AB  - In spite of the vast arsenal of therapeutic agents, therapy of herpes virus
      infection (HVI) is very difficult, particularly in pregnant women, newborns and
      children in the first years of life, as well as in patients with immune
      deficiency. In this regard, possibility of using immunoglobulins for the
      treatment of HVI is currently attracting the attention of doctors. The aim of
      this work was to develop a suppository form of the drug containing donor
      immunoglobulins with high levels of neutralizing antibodies to herpes simplex
      virus types 1 and 2 for the treatment of chronic forms of herpetic disease. The
      study included the following steps: 1) selection of gamma-globulins with high
      antibody titer for HSV-1 and HSV-2 ELISA test; 2) determination of the level of
      neutralizing antibodies in the selected series of gamma-globulins in tests in
      tissue cultures and animals; 3) lyophilization of immunoglobulins; 4) development
      of the suppository form of the preparation containing gamma-globulin donors with
      high levels of neutralizing antibodies to HSV-1 and HSV-2; 5) study of the safety
      of the activity of neutralizing antibodies to HSV-1 and HSV-2 in the suppository
      form of the drug with hyaluronic acid used as immunomodulator. As the result of
      this work, immunoglobulin preparation in the suppository form was developed. The
      developed preparation meets the requirements for safety and efficacy. It is not
      toxic or pyrogenic. The problems of clinical use of this drug as a method of HVI
      therapy are discussed.

PMID- 29323846
TI  - A comparative analysis of virucidal efficiency of biocide agents.
AB  - The main groups of biocide agents used for inactivation of bacteria and viruses
      were studied for their virucidal activity against enveloped (HIV, viral hepatitis
      C, influenza virus A) and non-enveloped viruses (poliovirus, adenovirus). Their
      efficiency was analyzed. Quarterly ammonium compounds (QAC) themselves are not
      able to properly inactivate non-enveloped viruses. However, they can be
      successfully applied in combination with other biocides (guanidines, aldehydes).
      Effective composition of QAC with amines and guanidines provided inactivation of
      viruses (4.0 lgTCID50) in concentrations of 0.166-0.280% for non-enveloped
      viruses and 0.080-00.185% for enveloped viruses. The combination of QAC with
      aldehydes is especially effective (0.04-0.64% for non-enveloped viruses). The
      virucidal efficiency does not directly depend on the QAC concentration in the
      chemical disinfectants.

PMID- 29323851
TI  - Buffalopox.
AB  - Buffalopox is a contagious viral disease affecting milch buffaloes (Bubalus
      Bubalis) and, rarely, cows. The disease has zoonotic implications, as outbreaks
      are frequently associated with human infections, particularly in the milkers.
      Buffalopox is associated with high morbidity (80%). The clinical symptoms of the
      disease are characterized by wartline lesions on the udder, teats, inguinal
      region, base of the ears, and over the parotid. In the severe form, generalized
      rash is observed. Although the disease does not lead to high mortality, it has an
      adverse effect on the productivity and working capacity of the animals resulting
      in large economic losses. The outbreaks of buffalopox occurred frequently in
      India, Pakistan, Bangladesh, Nepal, Iran, Egypt, and Indonesia, where buffaloes
      are reared as milch animals. The buffalopox is closely related with other
      Orthopoxviruses. In particular, it is close to the vaccinia virus. There is a
      view that the buffalopox virus might be derived from the vaccinia virus. It is
      possible that it became pathogenic to humans and animals through adaptive
      evolution of the genome by obtaining the virulence genes. PCR is performed for
      the C18L gene for the purpose of specific detection and differentiation of the
      buffalopox virus from other orthopoxviruses. The C18L gene encodes the ankyrin
      repeat protein, which determines the virus host range. The open reading frame of
      this gene is only 150-nucleotide long as against 453 nucleotide in the vaccinia
      virus, 756 - in the camelpox virus, and 759 - in the cowpox virus. It can be
      concluded that a systematic study based on the epidemiology of the virus,
      existence of reservoirs, biological transmission, and the molecular organization
      of the buffalopox virus from buffalo, cow, and humans may pave the way to a
      better understanding of the circulating virus and contribute to the control of
      the disease using the suitable diagnostic and prophylactic measures.

PMID- 29323852
TI  - Diagnostic value of the Epstein-Barr virus serological markers in patients with
      nasopharyngeal carcinoma in cases of undetectable primary tumor location.
AB  - The goal of this work was to describe a method for diagnosis of the non
      keratinizing nasopharyngeal carcinoma (nNPC) in cases of the undetectable primary
      tumor location. The method is based on evaluation of IgG and IgA antibody levels
      to the capsid (VCA) and early antigens (EA) of the Epstein-Barr virus (EBV). The
      diagnosis of nNPC is established by a so-called decision rule. The latter was
      created by mathematical processing of the method of multifactor analysis of the
      results of anti-EBV antibody testing of 72 patients with clinically and
      morphologically confirmed nNPC and 72 patients with other head and neck benign
      tumors (OHNT) not associated with EBV, which were tested as a control group. The
      diagnostic value of the decision rule which was tested in the group of 77
      patients with confirmed nNPC and 231 patients of a control group was high. The
      numbers of false negative and false positive cases were equal to 5.2% (4/77) and
      6.5% (17/231), respectively. Among 32 patients with undetectable primary tumors
      the decision rule was able to identify 11 cases of nNPC. This diagnosis later was
      confirmed by morphological and instrumental methods of study. Only in two cases,
      false negative result was obtained (2/32; 6.3%) indicating that the serological
      diagnostics of nNPC with the decision rule is highly specific but not exact.
      Thus, the data obtained allowed us to conclude that the serological testing of
      EBV specific antibody evaluated by the decision rule can be recommended as an
      important test supplementing the standard methods of pdNPC diagnostics including
      cases with undetected primary tumor location.

PMID- 29323853
TI  - IL17A gene polymorphisms: relationship to predisposition for chronic viral
      hepatitis and progression to liver cirrhosis in kazakh population.
AB  - Introduction: This work is the first genetic association study of a potential
      relationship of single nucleotide polymorphisms rs8193036 and rs2275913 located
      in the IL17A promoter on chromosome 6p12 to chronic viral hepatitis and its
      progression in Kazakh population. Purpose: Evaluation of the effect of IL17A
      polymorphism on predisposition for chronic hepatitis B and C and its progression
      to liver cirrhosis. Materials and Methods: A total of 862 individuals were
      enrolled in the retrospective case-control association study. Among the
      participants, 100 patients had chronic hepatitis B and/or C and liver cirrhosis,
      and 341 patients had chronic viral hepatitis only. Four hundred twenty-one (421)
      healthy HBV- and HCV-negative donors without liver diseases were recruited as
      population control. single nucleotide polymorphisms rs8193036[T/C] and
      rs2275913[G/A] were genotyped by TaqMan assays using genomic DNA extracted from
      peripheral blood cells. Results. Minor allele frequencies of rs8193036[C] and
      rs2275913[A] in the groups of patients were very similar to those observed in the
      control population, 0.4 and 0.3, respectively. Multivariate logistic regression
      analysis revealed odds ratios close to 1.0 and confidence intervals overlapping
      with the value of 1.0 and statistical significance p > 0.4 for any groups under
      comparison in the multiplicative model of inheritance. conclusion: No significant
      association between two single nucleotide polymorphisms, rs8193036 and rs2275913
      in the IL17A promoter, and susceptibility to chronic viral hepatitis C and/or B
      and disease progression to liver cirrhosis in Kazakh population were found.

PMID- 29323855
TI  - Analysis of the env gene variability of the IDU-A HIV-1 variant in the outbreak
      of the HIV infection epidemic in Perm region of Russia (1996-2011).
AB  - In the present work, a total of 132 HIV-1 env gene C2-V3-C3 sequences belonging
      to the IDU-A genetic variant were analyzed. The variants were obtained from the
      viruses circulating among IDUs and heterosexuals in the Perm region at different
      periods. It was shown that the rate of the divergence of the IDU-A HIV-1 viruses
      from a common ancestor increased 4.3 times (p < 0.001) in 2011 as compared with
      the onset of the epidemics. The rate of the HIV-1 evolution was different in the
      two risk groups of the infection. The mean genetic distance of HIV-1 variants
      circulating among heterosexuals was 1.3 times longer (p = 0.008) than that among
      IDUs. The accumulation rate of the nucleotide (including nonsynonymous)
      substitutions in the C2-V3-C3 HIV-1 env gene region among individuals infected by
      heterosexual contacts was 1.7 times higher than that among IDUs. The differences
      in the positions of the codons subjected to positive selection were demonstrated
      depending on the infection risk group tested.

PMID- 29323854
TI  - Immunofluorescence diagnosis of the herpesvirus stillborn infection.
AB  - Congenital herpes infection belongs to the category of actual problems of
      Perinatal Medicine. Pathological diagnosis of this disease is not effective in
      the routine method of autopsy studies without virological research. Objective.
      Determination of the value of the fluorescent antibody technique in the diagnosis
      of congenital herpes infection of the stillborn is a promising approach to
      medical diagnosis. subjects and methods. In 96 cases of stillbirth
      immunofluorescent identification of herpes simplex virus types 1 and 2 and
      cytomegalovirus in the placenta and internal organs (brain, heart, lungs, and
      liver) was implemented. The findings were compared with the results of a complete
      histological examination of the heart, including its rhythmogenic centers.
      Results. The herpes viruses were found in 51 observations (53.1%). Among them,
      HSV-1 were found in 16 observations (16.7%), HSV-2, in 19 (19.7%), CMV, in 16
      (16.7%). In 34 stillbirths (35.8%) the pathological signs of herpetic atrial
      myocarditis were observed, which were regarded as the cause of death. Conclusion.
      The use of the fluorescent antibody technique in the autopsy practice is an
      effective way of diagnosis of intrauterine infection caused by the herpes simplex
      virus and cytomegalovirus.

PMID- 29323856
TI  - Tick-borne encephalitis virus isolates from natural foci of the Irkutsk region:
      clarification of the genotype landscape.
AB  - The Irkutsk region is the unique territory where all known subtypes of tick-borne
      encephalitis virus (TBEV) circulate. In the last years, the phenomenon of changes
      in TBEV subtypes (substitution of the Far-Eastern subtype by the Siberian one)
      was noted in some regions of the Russian Federation. The results of individual
      investigation of 11522 Ixodes persulcatus ticks and brain specimens from 81 small
      mammals collected in natural foci of the Irkutsk region during 2006-2014 are
      presented in the article. More than 60 TBEV strains have been isolated and
      studied by virological methods; E gene fragments (1193 b.p.) of 68 isolates have
      been typed. The majority of the strains (irrespective of subtype) were of high
      virulence for laboratory mice (LM) in case of both intracerebral and subcutaneous
      inoculation of virus. All isolates from warm-blooded small mammals and humans
      were of high virulence for LM, but placed in the same clusters of the
      phylogenetic tree with ticks collected in the same area. Tick-borne strains of
      different virulence also did not form separate clusters on the tree. Phylogenetic
      analysis showed that modern TBEV genotypic landscape of the studied territory is
      changing toward absolute predominance of the Siberian subtype (94.1%). This
      subtype is represented by two groups with prototype strains "Zausaev" and
      "Vasilchenko". The "Vasilchenko" group of strains is spread on the whole
      territory under study; the strains of "Zausaev" group were isolated previously in
      the Irkutsk suburbs. The European subtype of TBEV circulates in natural foci of
      Pribaikalie permanently (at least 5% of the random sampling); the strains are of
      high virulence for LM. The Far-Eastern TBEV subtype was not found within the
      group of isolates collected in 20062014. The phylogenetic relationship of the
      strains under study had a higher correlation with the place of isolation than
      with the year or source.

PMID- 29323857
TI  - Development and evaluation of the RT-PCR kit for the rabies virus diagnosis.
AB  - To improve the diagnosis, surveillance, and control for the rabies virus, a kit
      for hybridization-triggered fluorescence detection of rabies virus DNA by the RT
      PCR technique was developed and evaluated. The analytical sensitivity of the kit
      was 4*10 GE per ml. High specificity of the kit was shown using representative
      sampling of viral, bacterial, and human nucleic acids.

PMID- 29323858
TI  - Calculated decisions: Absolute neutrophil count

PMID- 29323859
TI  - Calculated decisions: MASCC Risk Index for febrile neutropenia

PMID- 29323860
TI  - Editorial - Seeking a new 'normal' in the Canadian food environment.

PMID- 29323861
TI  - Commentary - What about the mouth? Connecting oral health and food environments.

PMID- 29323863
TI  - At-a-glance - "A tough sell": findings from a qualitative analysis on the
      provision of healthy foods in recreation and sports settings.
AB  - Recreation and sport settings (RSS) typically promote health in the form of
      physical activity, but the healthfulness of their food environment is often
      neglected. We explored stakeholder perspectives on barriers to healthy food
      provision in RSS through telephone interviews with ten representatives from RSS
      across Nova Scotia. Three key barriers were identified: 1) cultural norms
      associated with food in RSS and the broader environment, 2) the persisting notion
      of personal choice and responsibility, and 3) financial implications of healthy
      food provision. These barriers challenge healthy food provision in RSS and
      require multi-faceted strategies to overcome social norms that undermine health
      behaviours.

PMID- 29323862
TI  - Healthy food procurement and nutrition standards in public facilities: evidence
      synthesis and consensus policy recommendations.
AB  - INTRODUCTION: Unhealthy foods are widely available in public settings across
      Canada, contributing to diet-related chronic diseases, such as obesity. This is a
      concern given that public facilities often provide a significant amount of food
      for consumption by vulnerable groups, including children and seniors. Healthy
      food procurement policies, which support procuring, distributing, selling, and/or
      serving healthier foods, have recently emerged as a promising strategy to counter
      this public health issue by increasing access to healthier foods. Although
      numerous Canadian health and scientific organizations have recommended such
      policies, they have not yet been broadly implemented in Canada. METHODS: To
      inform further policy action on healthy food procurement in a Canadian context,
      we: (1) conducted an evidence synthesis to assess the impact of healthy food
      procurement policies on health outcomes and sales, intake, and availability of
      healthier food, and (2) hosted a consensus conference in September 2014. The
      consensus conference invited experts with public health/nutrition policy research
      expertise, as well as health services and food services practitioner experience,
      to review evidence, share experiences, and develop a consensus
      statement/recommendations on healthy food procurement in Canada. RESULTS:
      Findings from the evidence synthesis and consensus recommendations for healthy
      food procurement in Canada are described. Specifically, we outline
      recommendations for governments, publicly funded institutions, decision-makers
      and professionals, citizens, and researchers. CONCLUSION: Implementation of
      healthy food procurement policies can increase Canadians' access to healthier
      foods as part of a broader vision for food policy in Canada.

PMID- 29323864
TI  - Status report - FoodReach Toronto: lowering food costs for social agencies and
      community groups.
AB  - Toronto has the largest absolute number of food insecure households for any
      metropolitan census area in Canada: of its 2.1 million households, roughly 252
      000 households (or 12%) experience some level of food insecurity. Community
      organizations (including social agencies, school programs, and child care
      centres) serve millions of meals per year to the city's most vulnerable citizens,
      but often face challenges accessing fresh produce at affordable prices. Therefore
      in 2015, Toronto Public Health, in collaboration with public- and private-sector
      partners, launched the FoodReach program to improve the efficiency of food
      procurement among community organizations by consolidating their purchasing
      power. Since being launched, FoodReach has been used by more than 50 community
      organizations to provide many of Toronto's most marginalised groups with regular
      access to healthy produce.

PMID- 29323865
TI  - Building capacity through urban agriculture: report on the askiy project.
AB  - INTRODUCTION: Many North American cities have a built environment that provides
      access to energy-dense food and little opportunity for active living. Urban
      agriculture contributes to a positive environment involving food plant
      cultivation that includes processing, storing, distributing and composting. It is
      a means to increase local food production and thereby improve community health.
      The purpose of this study was to understand how participating in urban
      agriculture can help to empower young adults and build capacity for growing food
      in the city. METHODS: This was a qualitative study of seven participants (five
      Indigenous and two non-Indigenous) between the ages of 19 and 29 years, engaged
      as interns in an urban agriculture project known as "askiy" in Saskatoon,
      Saskatchewan, Canada in 2015. We used a case-study design and qualitative
      analysis to describe the participants' experience based on the sustainable
      livelihoods framework. RESULTS: A collaborative approach had a great effect on
      the interns' experiences, notably the connections formed as they planned,
      planted, tended, harvested and sold the produce. Some of the interns changed
      their grocery shopping habits and began purchasing more vegetables and
      questioning where and how the vegetables were produced. All interns were eager to
      continue gardening next season, and some were planning to take their knowledge
      and skills back to their home reserves. CONCLUSION: Urban agriculture programs
      build capacity by providing skills beyond growing food. Such programs can
      increase local food production and improve food literacy skills, social
      relationships, physical activity and pride in community settings.

PMID- 29323866
TI  - Correction: Soy Intake Is Associated with Increased 2-Hydroxylation and Decreased
      16-Hydroxylation of Estrogens in Asian-American Women

PMID- 29323867
TI  - Correction: Development and Cancer: At the Crossroads of Nodal and Notch
      Signaling

PMID- 29323868
TI  - Sequential Multicomponent Strategy for the Diastereoselective Synthesis of
      Densely Functionalized Spirooxindole-Fused Thiazolidines.
AB  - We developed two Ugi-type three-component reactions of spirooxindole-fused 3
      thiazolines, isocyanides, and either carboxylic acids or trimethylsilyl azide, to
      give highly functionalized spirooxindole-fused thiazolidines. Two diverse
      libraries were generated using practical and robust procedures affording the
      products in typically good yields. The obtained thiazolidines proved to be
      suitable substrates for further transformations. Notably, both the Ugi-Joullie
      and the azido-Ugi reactions resulted highly diastereoselective, affording
      predominantly the trans-configured products, as confirmed by X-ray
      crystallographic analysis.

PMID- 29323869
TI  - Dual-Functional Superhydrophobic Textiles with Asymmetric Roll-Down/Pinned States
      for Water Droplet Transportation and Oil-Water Separation.
AB  - Superhydrophobic surfaces with tunable adhesion from lotus-leaf to rose-petal
      states have generated much attention for their potential applications in self
      cleaning, anti-icing, oil-water separation, microdroplet transportation, and
      microfluidic devices. Herein we report a facile magnetic-field-manipulation
      strategy to fabricate dual-functional superhydrophobic textiles with asymmetric
      roll-down/pinned states on the two surfaces of the textile simultaneously. Upon
      exposure to a static magnetic field, fluoroalkylsilane-modified iron oxide (F
      Fe3O4) nanoparticles in polydimethylsiloxane (PDMS) moved along the magnetic
      field to construct discrepant hierarchical structures and roughnesses on the two
      sides of the textile. The positive surface (closer to the magnet, or P-surface)
      showed a water contact angle up to 165 degrees , and the opposite surface (or O
      surface) had a water contact angle of 152.5 degrees . The P-surface where water
      droplets easily slid off with a sliding angle of 7.5 degrees  appeared in the
      "roll-down" state as Cassie mode, while the O-surface was in the "pinned" state
      as Wenzel mode, where water droplets firmly adhered even at vertical (90 degrees
      ) and inverted (180 degrees ) angles. The surface morphology and wetting mode
      were adjustable by varying the ratios of F-Fe3O4 nanoparticles and PDMS. By
      taking advantage of the asymmetric adhesion behaviors, the as-fabricated
      superhydrophobic textile was successfully applied in no-loss microdroplet
      transportation and oil-water separation. Our method is simple and cost-effective.
      The fabricated textile has the characteristics of superhydrophobicity, magnetic
      responsiveness, excellent chemical stability, adjustable surface morphology, and
      controllable adhesion. Our findings conceivably stand out as a new tool to
      fabricate functional superhydrophobic materials with asymmetric surface
      properties for various potential applications.

PMID- 29323871
TI  - Microfluidic Device for Aptamer-Based Cancer Cell Capture and Genetic Mutation
      Detection.
AB  - We present a microfluidic device for specifically capturing cancer cells and
      isolating their genomic DNA (gDNA) for specific amplification and sequence
      analysis. To capture cancer cells within the device, nucleic acid aptamers that
      specifically bind to cancer cells were immobilized within a channel containing
      micropillars designed to increase capture efficiency. The captured cells were
      lysed in situ, and their gDNA was isolated by physical entanglement within a
      second smaller-dimensioned micropillar array. This type of isolation allows the
      gDNA to be retained and purified within the channel and enables amplification and
      analysis to be performed on the gDNA without the loss of the original template.
      We developed a technique for selectively amplifying genes from whole gDNA using
      multiple displacement amplification. The amplified gene samples were sequenced,
      and the resulting sequence information was compared against the known wild-type
      gene to identify any mutations. We have tested cervical and ovarian cancer cells
      for mutations in the TP53 gene using this technology. This approach offers a way
      to monitor multiple genetic mutations in the same small population of cells,
      which is beneficial given the wide diversity in cancer cells, and therefore it
      requires very few cells to be extracted from a patient sample.

PMID- 29323870
TI  - Cell Membrane Bioconjugation and Membrane-Derived Nanomaterials for
      Immunotherapy.
AB  - Cell membrane engineering, including live cell membrane bioconjugation and cell
      membrane-derived nanomaterials is a highly promising strategy to modulate immune
      responses for treating diseases. Many cell membrane engineering methods have
      potential for translation for human clinical use in the near future. In this
      Topical Review, we summarize the cell membrane conjugation strategies that have
      been investigated for cancer immunotherapy, the prevention of immune rejection to
      donor cells and tissues, and the induction of antigen-specific tolerance in
      autoimmune diseases. Additionally, cell membrane-derived or membrane-coated
      nanomaterials are an emerging class of nanomaterials that is attracting
      significant attention in the field of nanomedicine. Some of these nanomaterials
      have been employed to elicit immune responses against cancer, toxins, and
      bacteria, although their application in establishing immune tolerance has not
      been explored. In addition to discussing potential problems, we provide our
      perspectives for promising future directions.

PMID- 29323872
TI  - Glycodendrimer Nanocarriers for Direct Delivery of Fludarabine Triphosphate to
      Leukemic Cells: Improved Pharmacokinetics and Pharmacodynamics of Fludarabine.
AB  - Fludarabine, a nucleoside analogue antimetabolite, has complicated
      pharmacokinetics requiring facilitated transmembrane transport and intracellular
      conversion to triphosphate nucleotide form (Ara-FATP), causing it to be
      susceptible to emergence of drug resistance. We are testing a promising strategy
      to improve its clinical efficacy by direct delivery of Ara-FATP utilizing a
      biocompatible glycodendrimer nanocarrier system. Here, we present results of a
      proof-of-concept experiment in several in vitro-cultured leukemic cell lines
      (CCRF, THP-1, U937) using noncovalent complexes of maltose-modified
      poly(propyleneimine) dendrimer and fludarabine triphosphate. We show that Ara
      FATP has limited cytotoxic activity toward investigated cells relative to free
      nucleoside (Ara-FA), but complexation with the glycodendrimer (which does not
      otherwise influence cellular metabolism) drastically increases its toxicity.
      Moreover, we show that transport via hENT1 is a limiting step in Ara-FA toxicity,
      while complexation with dendrimer allows Ara-FATP to kill cells even in the
      presence of a hENT1 inhibitor. Thus, the use of glycodendrimers for drug delivery
      would allow us to circumvent naturally occurring drug resistance due to decreased
      transporter activity. Finally, we demonstrate that complex formation does not
      change the advantageous multifactorial intracellular pharmacodynamics of Ara
      FATP, preserving its high capability to inhibit DNA and RNA synthesis and induce
      apoptosis via the intrinsic pathway. In comparison to other nucleoside analogue
      drugs, fludarabine is hereby demonstrated to be an optimal candidate for maltose
      glycodendrimer-mediated drug delivery in antileukemic therapy.

PMID- 29323873
TI  - Silicon Rhodamine-Based Near-Infrared Fluorescent Probe for gamma
      Glutamyltransferase.
AB  - We designed and synthesized an activatable near-infrared (NIR) fluorescent probe
      for gamma-glutamyltransferase, based on an asymmetric silicon rhodamine scaffold
      with an optimized equilibrium of intramolecular spirocyclization. The synthesized
      probe exhibits dramatic NIR fluorescence activation and, in combination with
      previously reported probes, enables discrimination of tumors with different
      enzymatic profiles.

PMID- 29323874
TI  - Strategy of Solution-Processed All-Inorganic Heterostructure for
      Humidity/Temperature-Stable Perovskite Quantum Dot Light-Emitting Diodes.
AB  - Recently, a pressing requirement of solid-state lighting sources with high
      performance and low cost has motivated increasing research in metal halide
      perovskites. However, the relatively low emission efficiency and poor operation
      stability of perovskite light-emitting diodes (LEDs) are still critical
      drawbacks. In this study, a strategy of solution-processed all-inorganic
      heterostructure was proposed to overcome the emission efficiency and operation
      stability issues facing the challenges of perovskite LEDs. Solution-processed n
      ZnO nanoparticles and p-NiO are used as the carrier injectors to fabricate all
      inorganic heterostructured CsPbBr3 quantum dot LEDs, and a high-efficiency green
      emission is achieved with maximum luminance of 6093.2 cd/m2, external quantum
      efficiency of 3.79%, and current efficiency of 7.96 cd/A. More importantly, the
      studied perovskite LEDs possess a good operation stability after a long test time
      in air ambient. Typically, the devices can endure a high humidity (75%, 12 h) and
      a high working temperature (393 K, three heating/cooling cycles) even without
      encapsulation, and the operation stability is better than any previous reports.
      It is anticipated that this work will provide an effective strategy for the
      fabrication of high-performance perovskite LEDs with good stability under ambient
      and harsh conditions, making practical applications of such LEDs a real
      possibility.

PMID- 29323875
TI  - Theranostics of Triple-Negative Breast Cancer Based on Conjugated Polymer
      Nanoparticles.
AB  - Triple-negative breast cancer (TNBC) does not respond to many targeted drugs due
      to the lack of three receptors (i.e., estrogen receptor, progesterone receptor,
      and human epidermal growth factor receptor-2), which makes it difficult for TNBC
      detection and treatment. As compared to traditional breast cancer treatments such
      as surgery and chemotherapy, photodynamic therapy (PDT) has emerged as a
      promising approach for treating TNBC due to its precise controllability, high
      spatiotemporal accuracy, and minimal invasive nature. However, traditional
      photosensitizers used in PDT are associated with limitations of aggregation
      caused quenching (ACQ), and the ACQ induced a significant decrease in reactive
      oxygen species (ROS) generation. To address these, we synthesized a cyclic
      arginine-glycine-aspartic acid (cRGD) peptide-decorated conjugated polymer (CP)
      nanoparticles with poly[2-methoxy-5-(2-ethyl-hexyloxy)-1,4-phenylenevinylene]
      (MEH-PPV) as the photosensitizer for the theranostics of TNBC. The synthesized CP
      nanoparticles show bright fluorescence with high stability and could effectively
      produce ROS under light irradiation. Cell viability studies showed that the CP
      nanoparticles have negligible dark cytotoxicity and could efficiently kill the
      alphavbeta3 integrin-overexpressed MDA-MB-231 cells (one subtype of TNBC cells)
      in a selective way. With the use of cRGD-modified MEH-PPV nanoparticles as the
      theranostic agent, it permits targeted imaging and PDT of TNBC both in the in
      vitro 3D tumor model and in living mice. The application of CP nanoparticles in
      the successful theranostics of TNBC could pave the way for future development of
      CP-based photosensitizers for clinical applications.

PMID- 29323876
TI  - Revolutionizing Our Understanding of Amyloidogenic Proteins by Cryo-Electron
      Microscopy.

PMID- 29323877
TI  - Curcumin-Conjugated Gold Clusters for Bioimaging and Anticancer Applications.
AB  - Curcumin-conjugated gold clusters (CUR-AuNCs) were synthesized using a "green"
      procedure and utilized as an anticancer and a bioimaging agent. Curcumin is a
      well-known anticancer agent, which forms a cluster when reacting with a gold
      precursor under mild alkali condition. A fluorescence spectroscopy analysis
      showed that the CUR-AuNCs emitted red fluorescence (650 nm) upon visible light
      (550) irradiation. Fourier transform infrared spectroscopy analysis confirmed the
      stretching and bending nature between the gold atoms and curcumin. Meanwhile,
      transmission electron microscopy analysis showed a cluster of approximately 1-3
      nm with a uniform size. Time-resolved fluorescence analysis demonstrated that the
      red fluorescence was highly stable. Moreover, laser confocal imaging and atomic
      force microscopy analysis illustrated that a cluster was well distributed in the
      cell. This cluster exhibited less toxicity in the mortal cell line (COS-7) and
      high toxicity in the cervical cancer cell line (HeLa). The results demonstrated
      the conjugation of curcumin into the fluorescent gold cluster as a potential
      material for anticancer therapy and bioimaging applications.

PMID- 29323878
TI  - Electrical Matching at Metal/Molecule Contacts for Efficient Heterogeneous Charge
      Transfer.
AB  - In a metal/molecule hybrid system, unavoidable electrical mismatch exists between
      metal continuum states and frontier molecular orbitals. This causes energy loss
      in the electron conduction across the metal/molecule interface. For efficient use
      of energy in a metal/molecule hybrid system, it is necessary to control
      interfacial electronic structures. Here we demonstrate that electrical matching
      between a gold substrate and pi-conjugated molecular wires can be obtained by
      using monatomic foreign metal interlayers, which can change the degree of d-pi*
      back-donation at metal/anchor contacts. This interfacial control leads to energy
      level alignment between the Fermi level of the metal electrode and conduction
      molecular orbitals, resulting in resonant electron conduction in the
      metal/molecule hybrid system. When this method is applied to molecule-modified
      electrocatalysts, the heterogeneous electrochemical reaction rate is considerably
      improved with significant suppression of energy loss at the internal electron
      conduction.

PMID- 29323880
TI  - Photoactivated in Vitro Anticancer Activity of Rhenium(I) Tricarbonyl Complexes
      Bearing Water-Soluble Phosphines.
AB  - Fifteen water-soluble rhenium compounds of the general formula
      [Re(CO)3(NN)(PR3)]+, where NN is a diimine ligand and PR3 is 1,3,5-triaza-7
      phosphaadamantane (PTA), tris(hydroxymethyl)phosphine (THP), or 1,4-diacetyl
      1,3,7-triaza-5-phosphabicylco[3.3.1]nonane (DAPTA), were synthesized and
      characterized by multinuclear NMR spectroscopy, IR spectroscopy, and X-ray
      crystallography. The complexes bearing the THP and DAPTA ligands exhibit triplet
      based luminescence in air-equilibrated aqueous solutions with quantum yields
      ranging from 3.4 to 11.5%. Furthermore, the THP and DAPTA complexes undergo
      photosubstitution of a CO ligand upon irradiation with 365 nm light with quantum
      yields ranging from 1.1 to 5.5% and sensitize the formation of 1O2 with quantum
      yields as high as 70%. In contrast, all of the complexes bearing the PTA ligand
      are nonemissive and do not undergo photosubstitution upon irradiation with 365 nm
      light. These compounds were evaluated as photoactivated anticancer agents in
      human cervical (HeLa), ovarian (A2780), and cisplatin-resistant ovarian
      (A2780CP70) cancer cell lines. All of the complexes bearing THP and DAPTA
      exhibited a cytotoxic response upon irradiation with minimal toxicity in the
      absence of light. Notably, the complex with DAPTA and 1,10-phenanthroline gave
      rise to an IC50 value of 6 MUM in HeLa cells upon irradiation, rendering it the
      most phototoxic compound in this library. The nature of the photoinduced
      cytotoxicity of this compound was explored in further detail. These data indicate
      that the phototoxic response may result from the release of both CO and the
      rhenium-containing photoproduct, as well as the production of 1O2.

PMID- 29323881
TI  - Markov State Models: From an Art to a Science.
AB  - Markov state models (MSMs) are a powerful framework for analyzing dynamical
      systems, such as molecular dynamics (MD) simulations, that have gained widespread
      use over the past several decades. This perspective offers an overview of the MSM
      field to date, presented for a general audience as a timeline of key developments
      in the field. We sequentially address early studies that motivated the method,
      canonical papers that established the use of MSMs for MD analysis, and subsequent
      advances in software and analysis protocols. The derivation of a variational
      principle for MSMs in 2013 signified a turning point from expertise-driving MSM
      building to a systematic, objective protocol. The variational approach, combined
      with best practices for model selection and open-source software, enabled a wide
      range of MSM analysis for applications such as protein folding and allostery,
      ligand binding, and protein-protein association. To conclude, the current
      frontiers of methods development are highlighted, as well as exciting
      applications in experimental design and drug discovery.

PMID- 29323879
TI  - Malaria Derived Glycosylphosphatidylinositol Anchor Enhances Anti-Pfs25
      Functional Antibodies That Block Malaria Transmission.
AB  - Malaria, one of the most common vector borne human diseases, is a major world
      health issue. In 2015 alone, more than 200 million people were infected with
      malaria, out of which, 429 000 died. Even though artemisinin-based combination
      therapies (ACT) are highly effective at treating malaria infections, novel
      efforts toward development of vaccines to prevent transmission are still needed.
      Pfs25, a postfertilization stage parasite surface antigen, is a leading
      transmission-blocking vaccine (TBV) candidate. It is postulated that Pfs25
      anchors to the cell membrane using a glycosylphosphatidylinositol (GPI) linker,
      which itself possesses pro-inflammatory properties. In this study, Escherichia
      coli derived extract (XtractCF+TM) was used in cell free protein synthesis [CFPS]
      to successfully express >200 mg/L of recombinant Pfs25 with a C-terminal non
      natural amino acid (nnAA), namely, p-azidomethyl phenylalanine (pAMF), which
      possesses a reactive azide group. Thereafter, a unique conjugate vaccine (CV),
      namely, Pfs25-GPI was generated with dibenzocyclooctyne (DBCO) derivatized glycan
      core of malaria GPI using a simple but highly efficient copper free click
      chemistry reaction. In mice immunized with Pfs25 or Pfs25-GPI, the Pfs25-GPI
      group showed significantly higher titers compared to the Pfs25 group. Moreover,
      only purified IgGs from Pfs25-GPI group were able to significantly block
      transmission of parasites to mosquitoes, as judged by a standard membrane feeding
      assay [SMFA]. To our knowledge, this is the first report of the generation of a
      CV using Pfs25 and malaria specific GPI where the GPI is shown to enhance the
      ability of Pfs25 to elicit transmission blocking antibodies.

PMID- 29323882
TI  - Quantitative Shotgun Proteomics Associates Molecular-Level Cadmium Toxicity
      Responses with Compromised Growth and Reproduction in a Marine Copepod under
      Multigenerational Exposure.
AB  - In this study, the copepod Tigriopus japonicus was exposed to different cadmium
      (Cd) treatments (0, 2.5, 5, 10, and 50 MUg/L in seawater) for five generations
      (F0-F4), followed by a two-generation (F5-F6) recovery period in clean seawater.
      Six life-history traits (survival, developmental time of nauplius phase,
      developmental time to maturation, number of clutches, number of nauplii/clutch,
      and fecundity) were examined for each generation. Metal accumulation was also
      analyzed for generations F0-F6. Additionally, proteome profiling was performed
      for the control and 50 MUg/L Cd-treated F4 copepods. In F0-F4 copepods, Cd
      accumulated in a concentration-dependent manner, prolonging the development of
      the nauplius phase and maturation and reducing the number of nauplii/clutch and
      fecundity. However, during F5-F6, Cd accumulation decreased rapidly, and
      significant but subtle effects on growth and reproduction were observed only for
      the highest metal treatment at F5. Proteomic analysis revealed that Cd treatment
      had several toxic effects including depressed nutrient absorption, dysfunction in
      cellular redox homeostasis and metabolism, and oxidative stress, resulting in
      growth retardation and reproduction limitation in this copepod species. Taken
      together, our results demonstrate the relationship between molecular toxicity
      responses and population-level adverse outcomes in T. japonicus under
      multigenerational Cd exposure.

PMID- 29323883
TI  - A Stable Blue Photosensitizer for Color Palette of Dye-Sensitized Solar Cells
      Reaching 12.6% Efficiency.
AB  - We report a blue dye, coded as R6, which features a polycyclic aromatic
      hydrocarbon, 9,19-dihydrobenzo[1',10']phenanthro[3',4':4,5]thieno[3,2
      b]benzo[1,10]phenanthro[3,4-d]thiophene, coupled with a diarylamine electron
      donor and 4-(7-ethynylbenzo[c][1,2,5]thiadiazol-4-yl)benzoic acid acceptor. Dye
      R6 displays a brilliant sapphire color in a sensitized TiO2 mesoporous film with
      a Co(II/III) tris(bipyridyl)-based redox electrolyte. The R6 based dye-sensitized
      solar cell achieves an impressive power conversion efficiency of 12.6% under
      standard air mass 1.5 global, 100 mW cm-2, and shows a remarkable photostability.

PMID- 29323884
TI  - Drastic Redox Shift and Electronic Structural Changes of a Manganese(III)-Salen
      Oxidation Catalyst upon Reaction with Hydroxide and Cyanide Ion.
AB  - Flexible redox properties of a metal complex are important for redox catalysis.
      The present study shows that the reaction of a manganese(III) salen complex,
      which is a well-known oxidation catalyst, with hydroxide ion gives a transient
      manganese(III) species with drastically lowered redox potential, where the redox
      difference is -1.21 V. The reaction with cyanide ion gives a stable
      manganese(III) species with almost the same spectroscopic and redox properties,
      which was characterized as an anionic [MnIII(salen)(CN)2]- of low-spin S = 1
      state, in contrast to the starting MnIII(salen)(OTf) having usual high-spin S = 2
      manganese(III). The present study has thus clarified that the drastic redox shift
      comes from an anionic six-coordinate [MnIII(salen)(X)2]- species where X is
      either OH- or CN-. Resonance Raman measurements show that the stretching band of
      the imino group shifts from 1620 to 1597 cm-1 upon conversion from
      MnIII(salen)(OTf) to [MnIII(salen)(CN)2]-, indicative of lowered C?N double bond
      character for [MnIII(salen)(CN)2]-. The observed deformation of a salen ligand is
      a clear indication of an increased electron population on the imino pi*-orbital
      upon formation of low-spin manganese(III). It was proposed that the electronic
      structure of [MnIII(salen)(CN)2]- may contain only limited contribution from
      valence tautomeric [MnIV(salen- *)(CN)2]-, in which the imino group of a salen
      ligand is reduced by one-electron via intramolecular electron transfer from low
      spin manganese(III). The present study has clarified an unexpected new finding
      that a salen ligand works as a reservoir for negative charge to stabilize low
      spin manganese(III).

PMID- 29323885
TI  - Unraveling Hidden Mg-Mn-H Phase Relations at High Pressures and Temperatures by
      in Situ Synchrotron Diffraction.
AB  - The Mg-Mn-H system was investigated by in situ high pressure studies of reaction
      mixtures MgH2-Mn-H2. The formation conditions of two complex hydrides with
      composition Mg3MnH7 were established. Previously known hexagonal Mg3MnH7 (h
      Mg3MnH7) formed at pressures 1.5-2 GPa and temperatures between 480 and 500 
      degrees C, whereas an orthorhombic form (o-Mg3MnH7) was obtained at pressures
      above 5 GPa and temperatures above 600  degrees C. The crystal structures of the
      polymorphs feature octahedral [Mn(I)H6]5- complexes and interstitial H-.
      Interstitial H- is located in trigonal bipyramidal and square pyramidal
      interstices formed by Mg2+ ions in h- and o-Mg3MnH7, respectively. The hexagonal
      form can be retained at ambient pressure, whereas the orthorhombic form upon
      decompression undergoes a distortion to monoclinic Mg3MnH7 (m-Mg3MnH7). The
      structure elucidation of o- and m-Mg3MnH7 was aided by first-principles density
      functional theory (DFT) calculations. Calculated enthalpy versus pressure
      relations predict m- and o-Mg3MnH7 to be more stable than h-Mg3MnH7 above 4.3
      GPa. Phonon calculations revealed o-Mg3MnH7 to be dynamically unstable at
      pressures below 5 GPa, which explains its phase transition to m-Mg3MnH7 on
      decompression. The electronic structure of the quenchable polymorphs h- and m
      Mg3MnH7 is very similar. The stable 18-electron complex [MnH6]5- is mirrored in
      the occupied states, and calculated band gaps are around 1.5 eV. The study
      underlines the significance of in situ investigations for mapping reaction
      conditions and understanding phase relations for hydrogen-rich complex transition
      metal hydrides.

PMID- 29323886
TI  - Bisphenol F Disrupts Thyroid Hormone Signaling and Postembryonic Development in
      Xenopus laevis.
AB  - The safety of bisphenol A (BPA) alternatives has attracted much attention due to
      their wide use. In this study, we investigated the effects of bisphenol F (BPF),
      an alternative to BPA, on thyroid hormone (TH) signaling and postembryonic
      development in vertebrates using T3-induced and spontaneous Xenopus metamorphosis
      as models. We found that in the T3-induced metamorphosis assay, higher
      concentrations of BPF (100-10000 nM) antagonized T3-induced TH-response gene
      transcription and morphological changes including intestinal remodeling in a
      concentration-dependent manner, whereas 10 nM BPF exerted stimulatory effects on
      T3-induced integral metamorphosis when inhibited T3-induced TH-response gene
      transcription, demonstrating TH signaling disrupting effects of BPF. In the
      spontaneous metamorphosis assay, correspondingly, BPF inhibited development at
      metamorphic climax (with high endogenous TH levels), but promoted pre- and pro
      metamorphic development (with low endogenous TH levels), displaying a
      developmental stage-dependent manner. Importantly, we observed agonistic actions
      of BPF on Notch signaling in intestines, showing that BPF disrupts vertebrate
      development possibly via multi pathways besides TH signaling. Thus, we infer the
      biphasic concentration-response relationship between BPF exposure and T3-induced
      metamorphosis could result from the interactions of TH signaling with other
      signaling pathways such as Notch signaling. Our study highlights the adverse
      influences of BPF on vertebrate development.

PMID- 29323887
TI  - Benchmarking Excited-State Calculations Using Exciton Properties.
AB  - Benchmarking is an every-day task in computational chemistry, yet making
      meaningful comparisons between different methods is nontrivial. Benchmark studies
      often focus on the most obvious quantities such as energy differences. But to
      gain insight, it is desirable to explain the discrepancies between theoretical
      methods in terms of underlying wave functions and, consequently, physically
      relevant quantities. We present a new strategy of benchmarking excited-state
      calculations, which goes beyond excitation energies and oscillator strengths and
      involves the analysis of exciton properties based on the one-particle transition
      density matrix. By using this approach, we compare the performance of many-body
      excited-state methods (equation-of-motion coupled-cluster and algebraic
      diagrammatic construction) and time-dependent density functional theory. The
      selected examples illustrate the utility of different exciton descriptors in
      assigning state character and explaining the discrepancies among different
      methods. The examples include Rydberg, valence, and charge-transfer states, as
      well as delocalized excitonic states in large conjugated systems and states with
      substantial doubly excited character.

PMID- 29323889
TI  - Transmetalation for Flexible Pendant-Armed Schiff-Base Macrocyclic Complexes
      Influenced by Halide Effects.
AB  - Three 46-membered [2 + 2] pendant-armed Schiff-base macrocyclic dinuclear CdII
      and CuII complexes (2a, 2b, and 3b) and one 23-membered [1 + 1] CuII macrocycle
      4a were prepared from the template-directed condensation reactions between 1,2
      bis(2-aminoethoxy)-ethane and extended Cl-dialdehyde in the presence of CdX2 and
      CuX2 (X = Cl and Br), in which halide effects play important roles in the
      organization of final macrocyclic complexes in addition to the dominant influence
      of metal cations. Transmetalation was intensively studied among these CdII and
      CuII complexes with large and flexible macrocyclic ligands, including two
      previously synthesized dinuclear ZnII macrocycles (1a and 1b). Our results
      indicate that ZnII -> CuII and CdII -> CuII transmetalation proceeds more quickly
      than that from CdII to ZnII, and all the processes are found to be irreversible.
      It is noted that a [2 + 2] heterodinuclear CdIIZnII macrocyclic intermediate
      could be detected by ESI-MS together with [2 + 2] homodinuclear CdII and ZnII
      macrocyclic complexes. Furthermore, distinct halide behavior was observed in the
      in situ CdII -> CuII and ZnII -> CuII metal-ion exchange. That is to say, [2 + 2]
      macrocycles (1a and 2a) could be converted to [1 + 1] macrocycles 4a and 4b under
      the reflux condition in the case of CuCl2, accompanied by the configurational
      transformation from half-folded dinuclear ZnII and CdII to unfolded CuII
      macrocyclic skeleton. In contrast, CuBr2 leads to a highly efficient
      transmetalation to corresponding [2 + 2] dinuclear CuII complex 3b from both 1b
      and 2b no matter the experimental condition used.

PMID- 29323888
TI  - Covalent Immobilization of Cellulase Using Magnetic Poly(ionic liquid) Support:
      Improvement of the Enzyme Activity and Stability.
AB  - A magnetic nanocomposite was prepared by entrapment of Fe3O4 nanoparticles into
      the cross-linked ionic liquid/epoxy type polymer. The resulting support was used
      for covalent immobilization of cellulase through the reaction with epoxy groups.
      The ionic surface of the support improved the adsorption of enzyme, and a large
      amount of enzyme (106.1 mg/g) was loaded onto the support surface. The effect of
      the presence of ionic monomer and covalent binding of enzyme was also
      investigated. The structure of support was characterized by various instruments
      such as FT-IR, TGA, VSM, XRD, TEM, SEM, and DLS. The activity and stability of
      immobilized cellulase were investigated in the prepared support. The results
      showed that the ionic surface and covalent binding of enzyme onto the support
      improved the activity, thermal stability, and reusability of cellulase compared
      to free cellulase.

PMID- 29323890
TI  - High-Resolution Magic-Angle-Spinning NMR and Magnetic Resonance Imaging
      Spectroscopies Distinguish Metabolome and Structural Properties of Maize Seeds
      from Plants Treated with Different Fertilizers and Arbuscular mycorrhizal fungi.
AB  - Both high-resolution magic-angle-spinning (HRMAS) and magnetic resonance imaging
      (MRI) NMR spectroscopies were applied here to identify the changes of metabolome,
      morphology, and structural properties induced in seeds (caryopses) of maize
      plants grown at field level under either mineral or compost fertilization in
      combination with the inoculation by arbuscular mycorrhizal fungi (AMF). The
      metabolome of intact caryopses was examined by HRMAS-NMR, while the morphological
      aspects, endosperm properties and seed water distribution were investigated by
      MRI. Principal component analysis (PCA) was applied to evaluate 1H CPMG (Carr
      Purcel-Meiboom-Gill) HRMAS spectra as well as several MRI-derived parameters (
      T1, T2, and self-diffusion coefficients) of intact maize caryopses. PCA score
      plots from spectral results indicated that both seeds metabolome and structural
      properties depended on the specific field treatment undergone by maize plants.
      Our findings show that a combination of multivariate statistical analyses with
      advanced and nondestructive NMR techniques, such as HRMAS and MRI, enables the
      evaluation of the effects induced on maize caryopses by different fertilization
      and management practices at field level. The spectroscopic approach adopted here
      may become useful for the objective appraisal of the quality of seeds produced
      under a sustainable agriculture.

PMID- 29323891
TI  - C-H Arylation of Phenanthrene with Trimethylphenylsilane by Pd/o-Chloranil
      Catalysis: Computational Studies on the Mechanism, Regioselectivity, and Role of
      o-Chloranil.
AB  - The transition-metal-catalyzed C-H arylation of aromatic hydrocarbons represents
      a useful and ideal method for the production of biaryls and multiarylated
      aromatic compounds. We have previously reported the palladium-catalyzed direct C
      H arylation of polycyclic aromatic hydrocarbons, such as phenanthrene, pyrene,
      and corannulene with various organosilicon, -borane, and -germanium compounds. In
      these reactions, o-chloranil proved to be an essential and unique promoter
      (stoichiometrically as an oxidant) and arylation occurred exclusively at the K
      region. Herein, we report our mechanistic investigation of Pd/o-chloranil
      catalysis in C-H arylation of phenanthrene with trimethylphenylsilane by
      computational calculations. The results revealed that C-H arylation occurs
      through a sequence of transmetalation, carbometalation, and trans-beta-hydrogen
      elimination steps. In addition, the triple role of o-chloranil as a ligand,
      oxidant, and base is also elucidated.

PMID- 29323892
TI  - Same Substrate, Many Reactions: Oxygen Activation in Flavoenzymes.
AB  - Over time, organisms have evolved strategies to cope with the abundance of
      dioxygen on Earth. Oxygen-utilizing enzymes tightly control the reactions
      involving O2 mostly by modulating the reactivity of their cofactors. Flavins are
      extremely versatile cofactors that are capable of undergoing redox reactions by
      accepting either one electron or two electrons, alternating between the oxidized
      and the reduced states. The physical and chemical principles of flavin-based
      chemistry have been investigated widely. In the following pages we summarize the
      state of the art on a key area of research in flavin enzymology: the molecular
      basis for the activation of O2 by flavin-dependent oxidases and monooxygenases.
      In general terms, oxidases use O2 as an electron acceptor to produce H2O2, while
      monooxygenases activate O2 by forming a flavin intermediate and insert an oxygen
      atom into the substrate. First, we analyze how O2 reaches the flavin cofactor
      embedded in the protein matrix through dedicated access pathways. Then we
      approach O2 activation from the perspective of the monooxygenases, their
      preferred intermediate, the C(4a)-(hydro)peroxyflavin, and the cases in which
      other intermediates have been described. Finally, we focus on understanding how
      the architectures developed in the active sites of oxidases promote O2 activation
      and which other factors operate in its reactivity.

PMID- 29323894
TI  - Consensus Conformations of Dinucleoside Monophosphates Described with Well
      Converged Molecular Dynamics Simulations.
AB  - Dinucleoside monophosphates (DNMPs) have been described using various
      experimental approaches as flexible molecules which generate ensembles populating
      at least a small set of different conformations in solution. However, due to
      limitations of each approach in its ability to delineate the ensemble of
      conformations, an accurate and quantitative description of certain conformational
      features has not been performed for all DNMPs. Here, we apply a temperature
      replica-exchange molecular dynamics approach to fully and quickly converge
      conformational distributions of all RNA DNMPs immersed in the TIP3P water model
      using the AMBER ff14 force field. For a selection of DNMPs, the conformational
      ensembles were also generated when immersed in the OPC water model using
      alternative AMBER and CHARMM force fields. The OPC water model and other force
      field choices did not introduce new conformational classes but shifted the
      populations among existing conformations. Except for pyrimidine-pyrimidine
      dinucleosides, all other DNMPs populated four major conformations (which are
      defined in the main text and labeled A-form, Ladder, Inverted, and Sheared), in
      addition to an Extended form. Pyrimidine-pyrimidines did not generate the Sheared
      conformation. Distinguishing features and stabilizing factors of each
      conformation were identified and assessed based on the known experimental
      interpretations. The configuration of the glycosidic bond and the nonbonding
      interactions of hydrogen bond acceptors with the 2'-hydroxyl group were found to
      play determining roles in stabilizing particular conformations which could serve
      as a guide for potential force field modifications to improve the accuracy.
      Additionally, we computed stacking free energies based on the DNMP conformational
      distributions and found significant discrepancies with a previous study. Our
      investigation determined that the AMBER force field was incorrectly implemented
      in the previous study. In the future, this simulation approach can be used to
      quickly analyze the effects of new force field modifications in shifting the
      conformational populations of DNMPs, and can can be further applied to foresee
      such effects in larger RNA motifs including tetranucleotides and tetraloops.

PMID- 29323893
TI  - Modular [FeIII8MII6] n+ (MII = Pd, Co, Ni, Cu) Coordination Cages.
AB  - The reaction of the simple metalloligand [FeIIIL3] [HL = 1-(4-pyridyl)butane-1,3
      dione] with a variety of different MII salts results in the formation of a family
      of heterometallic cages of formulae [FeIII8PdII6L24]Cl12 (1),
      [FeIII8CuII6L24(H2O)4Br4]Br8 (2), [FeIII8CuII6L24(H2O)10](NO3)12 (3),
      [FeIII8NiII6L24(SCN)11Cl] (4), and [FeIII8CoII6L24(SCN)10(H2O)2]Cl2 (5). The
      metallic skeleton of each cage describes a cube in which the FeIII ions occupy
      the eight vertices and the MII ions lie at the center of the six faces. Direct
      current magnetic susceptibility and magnetization measurements on 3-5 reveal the
      presence of weak antiferromagnetic exchange between the metal ions in all three
      cases. Computational techniques known in theoretical nuclear physics as
      statistical spectroscopy, which exploit the moments of the Hamiltonian to
      calculate relevant thermodynamic properties, determine JFe-Cu = 0.10 cm-1 for 3
      and JFe-Ni = 0.025 cm-1 for 4. Q-band electron paramagnetic resonance spectra of
      1 reveal a significantly wider spectral width in comparison to [FeL3], indicating
      that the magnitude of the FeIII zero-field splitting is larger in the
      heterometallic cage than in the monomer.

PMID- 29323895
TI  - Computer-Assisted 3D Structure Elucidation (CASE-3D) of Natural Products
      Combining Isotropic and Anisotropic NMR Parameters.
AB  - A computer-assisted structural elucidation (CASE-3D) strategy based on the use of
      isotropic and/or anisotropic NMR data is proposed to elucidate relative
      configuration and preferred conformation in complex natural products. The
      methodology involves the selection of conformational models through the use of
      the Akaike Information Criterion and scoring of the different configurations. As
      illustrative examples, the methodology furnished the correct configuration of the
      already known compounds artemisinin (1) and homodimericin A (2). Revised
      structures (5 and 6), including their absolute configuration, for the recently
      reported curcusones I (3) and J (4) are proposed.

PMID- 29323896
TI  - Different Proteomic Processes Related to the Cultivar-Dependent Cadmium
      Accumulation of Amaranthus gangeticus.
AB  - To deal with the Cd contaminant of agricultural soil, pollution-safe cultivar
      (PSC) is developed to minimize the Cd accumulation risk in crops. The present
      study aimed to investigate the different proteomic responses related to Cd
      accumulation in different tissues between two Amaranthus gangeticus cultivars,
      Pen and Nan. A significantly higher Cd accumulation in Pen than in Nan was
      unraveled, especially in shoot. The proportions of soluble Cd in root and stem of
      Nan were significantly lower than those of Pen, implying lower Cd transportation
      from root to shoot in Nan. Higher contents of NaCl-extracted Cd in Pen than in
      Nan were probably attributed to the enhancement of GSH related metabolism in Pen,
      which activated the transportation of Cd from root to shoot. Alteration of other
      proteins involved in Cd detoxification and energy production also demonstrated
      that Pen had exhibited a stronger tolerance than Nan in dealing with Cd stress.
      Thus, differences in the proteomic processes associated with biochemical
      differences between the two typical cultivars suggested a cultivar-dependent
      capacity of Cd tolerance and accumulation in amaranth for the first time.

PMID- 29323897
TI  - A Series of Weakley-type Polyoxomolybdates: Synthesis, Characterization, and
      Magnetic Properties by a Combined Experimental and Theoretical Approach.
AB  - Using DCC as the dehydrating agent, a series of Weakley-type polyoxomolybdates
      [Bu4N]3{Ln[Mo5O13(OMe)4(NO)]2} (Ln = Tb, Dy, Ho, Er) were synthesized in a one
      pot reaction and structurally characterized by elemental, IR, UV-vis analysis,
      PXRD, and single-crystal X-ray diffraction. Furthermore, the static and dynamic
      measurements were utilized to investigate their magnetic performances. Typically,
      slow relaxation of magnetization was observed for Dy analogues with an energy
      barrier for the reversal of the magnetization of 50 K, which is the highest
      barrier height observed on the polyoxomolybdates-based single-molecule magnets
      (SMMs). For a deep understanding of the appearance of the SMM behavior on Weakley
      type polyoxomolybdates series, ab initio calculations on {Dy[Mo5O13(OMe)4(NO)]2}3
      have been conducted.

PMID- 29323898
TI  - Caliber Corrected Markov Modeling (C2M2): Correcting Equilibrium Markov Models.
AB  - Rate processes are often modeled using Markov State Models (MSMs). Suppose you
      know a prior MSM and then learn that your prediction of some particular
      observable rate is wrong. What is the best way to correct the whole MSM? For
      example, molecular dynamics simulations of protein folding may sample many
      microstates, possibly giving correct pathways through them while also giving the
      wrong overall folding rate when compared to experiment. Here, we describe Caliber
      Corrected Markov Modeling (C2M2), an approach based on the principle of maximum
      entropy for updating a Markov model by imposing state- and trajectory-based
      constraints. We show that such corrections are equivalent to asserting position
      dependent diffusion coefficients in continuous-time continuous-space Markov
      processes modeled by a Smoluchowski equation. We derive the functional form of
      the diffusion coefficient explicitly in terms of the trajectory-based
      constraints. We illustrate with examples of 2D particle diffusion and an
      overdamped harmonic oscillator.

PMID- 29323899
TI  - Optimization of Potent and Selective Tricyclic Indole Diazepinone Myeloid Cell
      Leukemia-1 Inhibitors Using Structure-Based Design.
AB  - Myeloid cell leukemia 1 (Mcl-1), an antiapoptotic member of the Bcl-2 family of
      proteins, has emerged as an attractive target for cancer therapy. Mcl-1
      upregulation is often found in many human cancers and is associated with high
      tumor grade, poor survival, and resistance to chemotherapy. Here, we describe a
      series of potent and selective tricyclic indole diazepinone Mcl-1 inhibitors that
      were discovered and further optimized using structure-based design. These
      compounds exhibit picomolar binding affinity and mechanism-based cellular
      efficacy, including growth inhibition and caspase induction in Mcl-1-sensitive
      cells. Thus, they represent useful compounds to study the implication of Mcl-1
      inhibition in cancer and serve as potentially useful starting points toward the
      discovery of anti-Mcl-1 therapeutics.

PMID- 29323900
TI  - Enantioselective 1,2-Anionotropic Rearrangement of Acylsilane through a
      Bisguanidinium Silicate Ion Pair.
AB  - Highly enantioselective bisguanidinium-catalyzed tandem rearrangements of
      acylsilanes are reported. The acylsilanes were activated via an addition of
      fluoride on the silicon to form a penta-coordinate anionic silicate intermediate.
      The silicate then underwent alkyl or aryl group migration from the silicon atom
      to the neighboring carbonyl carbon atom (1,2-anionotropic rearrangement),
      followed by [1,2]-Brook rearrangement to provide the secondary alcohols in high
      yields with excellent enantioselectivities (up to 95% ee). The isolation of an
      alpha-silylcarbinol intermediate as well as DFT calculations revealed that the
      1,2-anionotropic rearrangement occurred via a bisguanidinium silicate ion pair,
      which is the stereodetermining step. The chiral center formed is then retained
      without inversion through the subsequent [1,2]-Brook rearrangement. Crotyl
      acylsilanes were smoothly transformed into homoallylic linear crotyl alcohols
      with retention of E/Z geometry, and no branched alcohols were detected. This
      clearly suggested that the 1,2-anionotropic rearrangement occurred through a
      three-membered instead of a five-membered transition state.

PMID- 29323901
TI  - Microbial Biosynthesis of Silver Nanoparticles in Different Culture Media.
AB  - Microbial biosynthesis of metal nanoparticles has been extensively studied for
      the applications in biomedical sciences and engineering. However, the mechanism
      for their synthesis through microorganism is not completely understood. In this
      study, several culture media were investigated for their roles in the microbial
      biosynthesis of silver nanoparticles (AgNPs). The size and morphology of the
      synthesized AgNPs were analyzed by UV-vis spectroscopy, Fourier-transform
      infrared (FT-IR), transmission electron microscopy (TEM), and dynamic light
      scattering (DLS). The results demonstrated that nutrient broth (NB) and Mueller
      Hinton broth (MHB) among tested media effectively reduced silver ions to form
      AgNPs with different particle size and shape. Although the involved microorganism
      enhanced the reduction of silver ions, the size and shape of the particles were
      shown to mainly depend on the culture media. Our findings suggest that the growth
      media of bacterial culture play an important role in the synthesis of metallic
      nanoparticles with regard to their size and shape. We believe our findings would
      provide useful information for further exploration of microbial biosynthesis of
      AgNPs and their biomedical applications.

PMID- 29323902
TI  - Maillard Conjugation of Sodium Alginate to Whey Protein for Enhanced Resistance
      to Surfactant-Induced Competitive Displacement from Air-Water Interfaces.
AB  - Whey protein adsorbed to an interface forms a viscoelastic interfacial film but
      is displaced competitively from the interface by a small-molecule surfactant
      added afterward. The present study evaluated the impact of the covalent
      conjugation of high- or low-molecular-weight sodium alginate (HA or LA) to whey
      protein isolate (WPI) via the Maillard reaction on the ability of whey protein to
      resist surfactant-induced competitive displacement from the air-water interface.
      Surfactant added after the pre-adsorption of conjugate to the interface increased
      surface pressure. At a given surface pressure, the WPI-LA conjugate showed a
      significantly higher interfacial area coverage and lower interfacial film
      thickness compared to those of the WPI-HA conjugate or unconjugated WPI. The
      addition of LA to the aqueous phase had little effect on the interfacial area and
      thickness of pre-adsorbed WPI. These results suggest the importance of the
      molecular weight of the polysaccharide moiety in determining interfacial
      properties of whey protein-alginate conjugates.

PMID- 29323904
TI  - [4 + 2] Cyclization of para-Quinone Methide Derivatives with Alkynes.
AB  - The first cyclization of para-quinone methide derivatives with alkynes was
      established by utilizing the [4 + 2] reaction of ortho-hydroxyphenyl-substituted
      para-quinone methides with ynones or benzyne, which efficiently constructed the
      scaffolds of chromene and xanthene in high yields (up to 88%). This protocol has
      not only fulfilled the task of developing cyclization reactions of para-quinone
      methide derivatives but also provided an efficient method for constructing
      chromene and xanthene scaffolds.

PMID- 29323903
TI  - Development of a Scalable, Chromatography-Free Synthesis of t-Bu-SMS-Phos and
      Application to the Synthesis of an Important Chiral CF3-Alcohol Derivative with
      High Enantioselectivity Using Rh-Catalyzed Asymmetric Hydrogenation.
AB  - A chromatography-free, asymmetric synthesis of the C2-symmetric P-chiral
      diphosphine t-Bu-SMS-Phos was developed using a chiral auxiliary-based approach
      in five steps from the chiral auxiliary in 36% overall yield. Separtion and
      recovery of the auxiliary were achieved with good yield (97%) to enable recycling
      of the chiral auxiliary. An air-stable crystalline form of the final ligand was
      identified to enable isolation of the final ligand by crystallization to avoid
      chromatography. This synthetic route was applied to prepare up to 4 kg of the
      final ligand. The utility of this material was demonstrated in the asymmetric
      hydrogenation of trifluoromethyl vinyl acetate at 0.1 mol % Rh loading to access
      a surrogate for the pharmaceutically relavent chiral trifluoroisopropanol
      fragment in excellent yield and enantiomeric excess (98.6%).

PMID- 29323905
TI  - A Palladium Iodide-Catalyzed Oxidative Aminocarbonylation-Heterocyclization
      Approach to Functionalized Benzimidazoimidazoles.
AB  - A novel carbonylative approach to the synthesis of functionalized 1H
      benzo[d]imidazo[1,2-a]imidazoles is presented. The method consists of the
      oxidative aminocarbonylation of N-substituted-1-(prop-2-yn-1-yl)-1H
      benzo[d]imidazol-2-amines, carried out in the presence of secondary nucleophilic
      amines, to give the corresponding alkynylamide intermediates, followed by in situ
      conjugated addition and double-bond isomerization, to give 2-(1-alkyl-1H
      benzo[d]imidazo[1,2-a]imidazol-2-yl)acetamides. Products were obtained in good to
      excellent yields (64-96%) and high turnover numbers (192-288 mol of product per
      mol of catalyst) under relatively mild conditions (100  degrees C under 20 atm of
      a 4:1 mixture of CO-air), using a simple catalytic system, consisting of PdI2
      (0.33 mol %) in conjunction with KI (0.33 equiv).

PMID- 29323906
TI  - Theoretical Study of the Metal-Controlled Dehydrogenation Mechanism of MN2H3BH3
      (M = Li, Na, K): A New Family of Hydrogen Storage Material.
AB  - Metal hydrazineboranes (MHBs), as a kind of new hydrogen storage materials, show
      excellent hydrogen storage performance and dehydrogenation properties. Herein, we
      designed multiple dehydrogenation pathways to compare the metal-controlled
      effect. Quantum chemistry theory is used to calculate the crystal structure for
      determining the molecular structure. With an increase of the metal radius, the
      energy difference of the isomers also increases. The dehydrogenation pathways of
      lithium hydrazineborane (path A) and sodium hydrazineborane (path B) appear
      totally similar to each other in the dehydrogenation process despite the energy
      barrier, as well as the comparison paths A' (for LiHB) and B' (for NaHB). In
      contrast with LiHB and NaHB, the tautomeric reaction occurs in the potassium
      hydrazineborane (KHB) first, and the following dehydrogenation path is similar to
      that of the LiHB and NaHB. It explores the hydrogen-release properties of the
      different metal hydrazineboranes and also indcates the affection of the metal in
      the metal hydrazineboranes hydrogen-storage system.

PMID- 29323907
TI  - Ultrathin Semiconducting Bi2Te2S and Bi2Te2Se with High Electron Mobilities.
AB  - High carrier mobility and moderate band gap are two key properties of electronic
      device applications. Two ultrathin two-dimensional (2D) semiconductors, namely,
      Bi2Te2S and Bi2Te2Se nanosheets, with novel electronic and optical properties are
      predicted based on first-principles calculations. The Bi2Te2S and Bi2Te2Se
      monolayers own moderate band gaps (~0.7 eV) and high electron mobilities (~20 000
      cm2 V-1 s-1), and they can absorb sunlight efficiently through the whole incident
      solar spectrum. Meanwhile, layer-dependent exponential decay band gaps are also
      unveiled. The relatively low interlayer binding energies suggest that these
      monolayers can be easily exfoliated from bulk structures. Their high dynamical
      and thermal stabilities are further verified by phonon dispersion calculations
      and ab initio molecular dynamics simulations. The exceptional properties render
      Bi2Te2X (X = S, Se) monolayers promising candidates in future high-speed
      (opto)electronic devices.

PMID- 29323908
TI  - Correction to "Determination of Equilibrium Constant and Relative Brightness in
      FRET-FCS by Including the Third-Order Correlations".

PMID- 29323909
TI  - Synthesis of an Enantiomerically Pure Inherently Chiral Calix[4]Arene Phosphonic
      Acid and Its Evaluation as an Organocatalyst.
AB  - A facile method for the preparation of enantiomerically pure inherently chiral
      calix[4]arene phosphonic acid (cR,pR)-7 in four steps starting from the readily
      available and previously synthesized (cS)-enantiomer of calix[4]arene acetic acid
      1 or its methyl ester 2 was developed. The first tests of this unique calixarene
      Bronsted acid with inherent chirality in organocatalysis of the aza-Diels-Alder
      reaction of imines with Danishefsky's diene and epoxide ring opening by benzoic
      acid were performed. The calixarene phosphonic acid (cR,pR)-7 shows good
      catalytic activities but with low enantioselectivities in these reactions.

PMID- 29323910
TI  - Direct Synthesis of Prussian Blue Nanoparticles in Liposomes Incorporating
      Natural Ion Channels for Cs+ Adsorption and Particle Size Control.
AB  - Coordination polymer (CP) nanoparticles (NPs) formed by a self-assembly of
      organic ligands and metal ions are one of the attractive materials for molecular
      capture and deliver/release in aqueous media. Control of particle size and
      prevention of aggregation among CP NPs are important factors for improving their
      adsorption capability in water. We demonstrate here the potential of a liposome
      incorporating an antibiotic ion channel as a vessel for synthesizing Prussian
      blue (PB) NPs, being a typical CP. In the formation of PB NPs within liposomes,
      the influx rate of Fe2+ ions into liposome encapsulated [Fe(CN)6]3- through
      channels was fundamental for the change of NPs' sizes. The optimized PB NP
      liposome composite showed higher adsorption capacity of Cs+ ions than that of
      aggregated PB NPs that are prepared without liposome in aqueous media.

PMID- 29323911
TI  - Capillary Condensation in 8 nm Deep Channels.
AB  - Condensation on the nanoscale is essential to understand many natural and
      synthetic systems relevant to water, air, and energy. Despite its importance, the
      underlying physics of condensation initiation and propagation remain largely
      unknown at sub-10 nm, mainly due to the challenges of controlling and probing
      such small systems. Here we study the condensation of n-propane down to 8 nm
      confinement in a nanofluidic system, distinct from previous studies at ~100 nm.
      The condensation initiates significantly earlier in the 8 nm channels, and it
      initiates from the entrance, in contrast to channels just 10 times larger. The
      condensate propagation is observed to be governed by two liquid-vapor interfaces
      with an interplay between film and bridging effects. We model the experimental
      results using classical theories and find good agreement, demonstrating that this
      8 nm nonpolar fluid system can be treated as a continuum from a thermodynamic
      perspective, despite having only 10-20 molecular layers.

PMID- 29323912
TI  - Evaluation of Diarylheptanoid-Terpene Adduct Enantiomers from Alpinia officinarum
      for Neuroprotective Activities.
AB  - Two pairs of new diarylheptanoid-monoterpene adduct enantiomers, (+/-)
      alpininoids A and B [(+/-)-1 and (+/-)-2], as well as three pairs of new
      diarylheptanoid-sesquiterpene adduct enantiomers, (+/-)-alpininoids C-E [(+/-)-3
      (+/-)-5], together with four known diarylheptanoids (6-9) were isolated from the
      rhizomes of Alpinia officinarum. Their structures with absolute configurations
      were elucidated on the basis of comprehensive spectroscopic analyses and
      computational calculation methods. The skeletons of these cyclohexene-containing
      hybrid natural products were hypothesized to be generated via a crucial Diels
      Alder cycloaddition between the diarylheptanoids (7 and 8) and terpenes, of which
      1 represents a new carbon skeleton. All isolated compounds were evaluated for
      their neuroprotective effects against MPP+ (1-methyl-4-phenylpyridinium)-induced
      cortical neuron injury. At a concentration of 16 MUM, (+)-1 significantly
      increased cell viability when compared with MPP+ treatment alone.

PMID- 29323914
TI  - Path to the Desensitized State of Ligand-Gated Ion Channels: Why Are Inhibitory
      and Excitatory Receptors Different?
AB  - The family of pentameric ligand-gated ion channels (pLGICs) includes both
      inhibitory and excitatory receptors. Electrophysiological methods have explored
      the time-dependent ion currents induced by their neurotransmitter agonists.
      Kinetic modeling requires a minimum of three conformational states: resting,
      active, and desensitized. However, current traces of inhibitory and excitatory
      pLGICs differ substantially. Reproducing their basic features requires different
      state connectivity: whether the desensitized state is accessed from the resting
      or active state. It is surprising that a property as fundamental as state
      connectivity would differ within the same family. So, we explore the possibility
      that the connectivity is the same, but corresponding states differ in function:
      Analogous states on the free energy landscape have similar structure, but differ
      in ion conductivity, free energies, and agonist binding affinities. This
      hypothesis is tested using a kinetic model in which agonist and anesthetics
      modulate the receptor free energy landscape by adsorbing to the membrane in which
      the receptor is embedded. It was previously shown that even with only three
      states, the complex behavior observed for GABAAR is reproduced, including its
      response to anesthetics. It is demonstrated here that this hypothesis accounts
      for an important difference between inhibitory and excitatory receptors: their
      opposite responses to inhalation anesthetics.

PMID- 29323913
TI  - Nanoparticles with CD44 Targeting and ROS Triggering Properties as Effective in
      Vivo Antigen Delivery System.
AB  - Currently, development of subunit vaccine based on recombinant antigens or
      peptides has gradually become an important alternative option for traditional
      vaccine. However, induction of potent immune response with desired efficacy
      remains a major challenge. The nanoparticle-based antigen delivery system has
      been considered a potential carrier system to improve the efficacy of subunit
      vaccine. In the present study, we have designed an immune-stimulatory delivery
      system by conjugating three-armed PLGA to PEG via the peroxalate ester bond which
      is sensitive to hydrogen peroxide (H2O2), a major reactive oxygen species (ROS).
      Hyaluronic acid (HA), a ligand for CD44 receptors was also modified onto the
      outer shell of the 3s-PLGA-PEG nanoparticles to promote immune cell uptake. For
      in vitro and in vivo immune response assessment, a model antigen ovalbumin (OVA)
      was enclosed within the core of the 3s-PLGA-PEG nanoparticles to form 3s-PLGA-PO
      PEG/HA nanoparticles (PHO NPs). Our results showed that the PHO NPs enhanced
      dendritic cell maturation, antigen uptake, and antigen presentation in vitro,
      likely due to enhanced lysosomal escape. In vivo experiments further revealed
      that the PHO nanovaccine robustly promoted OVA-specific antibody production and T
      cell response accompanied by modest stimulation of memory T cells. In summary,
      the ROS-responsive PHO NPs with modified HA may be an effective vehicle antigen
      delivery system to promote antigen-induced immune response.

PMID- 29323915
TI  - Resonance Energy Transfer-Promoted Photothermal and Photodynamic Performance of
      Gold-Copper Sulfide Yolk-Shell Nanoparticles for Chemophototherapy of Cancer.
AB  - Gold (Au) core@void@copper sulfide (CuS) shell (Au-CuS) yolk-shell nanoparticles
      (YSNPs) were prepared in the present study for potential chemo-, photothermal,
      and photodynamic combination therapy, so-called "chemophototherapy". The
      resonance energy transfer (RET) process was utilized in Au-CuS YSNPs to achieve
      both enhanced photothermal and photodynamic performance compared with those of
      CuS hollow nanoparticles (HNPs). A series of Au nanomaterials as cores that had
      different localized surface plasmon resonance (LSPR) absorption peaks at 520,
      700, 808, 860, and 980 nm were embedded in CuS HNPs to screen the most effective
      Au-CuS YSNPs according to the RET process. Thermoresponsive polymer was
      fabricated on these YSNPs' surface to allow for controlled drug release. Au808
      CuS and Au980-CuS YSNPs were found capable of inducing the largest temperature
      elevation and producing the most significant hydroxyl radicals under 808 and 980
      nm laser irradiation, respectively, which could accordingly cause the most severe
      4T1 cell injury through oxidative stress mechanism. Moreover, doxorubicin-loaded
      (Dox-loaded) P(NIPAM-co-AM)-coated Au980-CuS (p-Au980-CuS@Dox) YSNPs could more
      efficiently kill cells than unloaded particles upon 980 nm laser irradiation.
      After intravenous administration to 4T1 tumor-bearing mice, p-Au980-CuS YSNPs
      could significantly accumulate in the tumor and effectively inhibit the tumor
      growth after 980 nm laser irradiation, and p-Au980-CuS@Dox YSNPs could further
      potentiate the inhibition efficiency and exhibit excellent in vivo
      biocompatibility. Taken together, this study sheds light on the rational design
      of Au-CuS YSNPs to offer a promising candidate for chemophototherapy.

PMID- 29323916
TI  - Influence of Eugenol on the Organization and Dynamics of Lipid Membranes: A Phase
      Dependent Study.
AB  - Eugenol is known for its antimicrobial effects against microorganisms responsible
      for infectious diseases in humans, food-borne pathogens, and oral pathogens. In
      spite of several reports on the antimicrobial function of eugenol by modulating
      the structural properties of cell membranes, there is limited information on the
      influence of eugenol in the lipid membrane. In this work, we explored the effect
      of eugenol on the organization and dynamics of large unilamellar vesicles (LUVs)
      of DMPC using the intrinsic fluorescence of eugenol and an extrinsic hydrophobic
      probe, DPH, in varying phases. The organization and dynamics of the bilayers of
      DMPC vesicles were monitored by utilizing varieties of steady-state and time
      resolved fluorescence measurements. Our results show that eugenol stabilizes the
      gel phase and elevates the phase-transition temperature of DMPC in a
      concentration-dependent fashion. Fluorescence lifetime measurements demonstrate
      that higher eugenol-induced water penetration was observed in fluid-phase
      membranes. Time-resolved anisotropy measurements demonstrate that eugenol reduces
      the semiangle of DPH wobbling-in-a-cone in gel-phase membranes, whereas the
      semiangle remains unaffected in fluid-phase membrane. This implies that the
      eugenol further orders the gel-phase membrane, and this could be a plausible
      reason for the eugenol-dependent elevation of the phase-transition temperature of
      DMPC. We envisage that these results will contribute important information to
      understand the interaction of eugenol with biological membranes.

PMID- 29323917
TI  - Effects of Acyl Chain Unsaturation on Activation Energy of Water Permeability
      across Droplet Bilayers of Homologous Monoglycerides: Role of Cholesterol.
AB  - Cholesterol is an important component of total lipid in mammalian cellular
      membranes; hence, the knowledge of its association with lipid bilayer membranes
      will be essential to understanding membrane structure and function. A droplet
      interface bilayer (DIB) provides a convenient and reliable platform through which
      values for permeability coefficient and activation energy of water transport
      across the membrane can be extracted. In this study, we investigated the effect
      of acyl chain structure in amphiphilic monoglycerides on the permeability of
      water across DIB membranes composed of cholesterol and these monoglycerides,
      where the acyl chain length, number of double bonds, and the position of double
      bond are varied systematically along the acyl chains. To elucidate the role of
      cholesterol in these membranes, we investigated its influence on water
      permeability and associated activation energies at two different cholesterol
      concentrations. Our systematic studies show dramatic sensitivity and selectivity
      of specific interaction of cholesterol with the monoglyceride bilayer having
      structural variations in acyl chain compositions. Our findings allow us to
      delineate the exquisite interplay between membrane properties and structural
      components and understand the balanced contribution of each.

PMID- 29323918
TI  - Responsive Hydrogel-based Photonic Nanochains for Microenvironment Sensing and
      Imaging in Real Time and High Resolution.
AB  - Microenvironment sensing and imaging are of importance in microscale zones like
      microreactors, microfluidic systems, and biological cells. But they are so far
      implemented only based on chemical colors from dyes or quantum dots, which
      suffered either from photobleaching, quenching, or photoblinking behaviors, or
      from limited color gamut. In contrast, structural colors from hydrogel-based
      photonic crystals (PCs) may be stable and tunable in the whole visible spectrum
      by diffraction peak shift, facilitating the visual detection with high accuracy.
      However, the current hydrogel-based PCs are all inappropriate for microscale
      detection due to the bulk size. Here we demonstrate the smallest hydrogel-based
      PCs, responsive hydrogel-based photonic nanochains with high-resolution and real
      time response, by developing a general hydrogen bond-guided template
      polymerization method. A variety of mechanically separated stimuli-responsive
      hydrogel-based photonic nanochains have been obtained in a large scale including
      those responding to pH, solvent, and temperature. Each of them has a
      submicrometer diameter and is composed of individual one-dimensional periodic
      structure of magnetic particles locked by a tens-of-nanometer-thick peapod-like
      responsive hydrogel shell. Taking the pH-responsive hydrogel-based photonic
      nanochains, for example, pH-induced hydrogel volume change notably alters the
      nanochain length, resulting in a significant variation of the structural color.
      The submicrometer size endows the nanochains with improved resolution and
      response time by 2-3 orders of magnitude than the previous counterparts. Our
      results for the first time validate the feasibility of using structural colors
      for microenvironment sensing and imaging and may further promote the applications
      of responsive PCs, such as in displays and printing.

PMID- 29323919
TI  - Effects of Aggregate Charge and Subphase Ionic Strength on the Properties of
      Spread Polyelectrolyte/Surfactant Films at the Air/Water Interface under Static
      and Dynamic Conditions.
AB  - We demonstrate the ability to tune the formation of extended structures in films
      of poly(sodium styrenesulfonate)/dodecyltrimethylammonium bromide at the
      air/water interface through control over the charge/structure of aggregates as
      well as the ionic strength of the subphase. Our methodology to prepare loaded
      polyelectrolyte/surfactant films from self-assembled liquid crystalline
      aggregates exploits their fast dissociation and Marangoni spreading of material
      upon contact with an aqueous subphase. This process is proposed as a potential
      new route to prepare cheap biocompatible films for transfer applications. We show
      that films spread on water from swollen aggregates of low/negative charge have
      1:1 charge binding and can be compressed only to a monolayer, beyond which
      material is lost to the bulk. For films spread on water from compact aggregates
      of positive charge, however, extended structures of the two components are
      created upon spreading or upon compression of the film beyond a monolayer. The
      application of ellipsometry, Brewster angle microscopy, and neutron reflectometry
      as well as measurements of surface pressure isotherms allow us to reason that
      formation of extended structures is activated by aggregates embedded in the film.
      The situation upon spreading on 0.1 M NaCl is different as there is a high
      concentration of small ions that stabilize loops of the polyelectrolyte upon film
      compression, yet extended structures of both components are only transient.
      Analogy of the controlled formation of extended structures in fluid monolayers is
      made to reservoir dynamics in lung surfactant. The work opens up the possibility
      to control such film dynamics in related systems through the rational design of
      particles in the future.

PMID- 29323920
TI  - Aerobic, Diselenide-Catalyzed Redox Dehydration: Amides and Peptides.
AB  - At 2.5 mol % loadings using reaction temperatures between 30-55  degrees C, ortho
      functionalized diaryl diselenides are highly effective organocatalytic oxidants
      for aerobic redox dehydrative amidic and peptidic bond formation using triethyl
      phosphite as a simple terminal reductant. This simple-to-perform organocatalytic
      reaction relies on the ability of selenols to react directly with dioxygen in air
      without recourse to metal catalysts. It represents an important step toward the
      development of a general, economical, and benign catalytic redox dehydration
      protocol.

PMID- 29323921
TI  - Membrane Anchoring of alpha-Helical Proteins: Role of Tryptophan.
AB  - The function of membrane proteins relies on a defined orientation of protein
      relative to lipid. In apparent correlation to protein anchoring, tryptophan
      residues are enriched in the lipid headgroup region. To characterize the
      thermodynamic and structural basis of this relationship in alpha-helical membrane
      proteins, we examined the role of three conserved tryptophans in the folding of
      the heterodimeric integrin alphaIIbbeta3 transmembrane (TM) complex in
      phospholipid bicelles and mammalian membranes. In the homogenous lipid
      environment of bicelles, tryptophan was replaceable by residues of distinct
      polarities. The appropriate polarity was guided by the electrostatic potential of
      the tryptophan surrounding, suggesting that tryptophan can complement diverse
      environments by adjusting the orientation of its anisotropic side chain to
      achieve site-specific anchoring. As a sole membrane anchor, tryptophan made a
      contribution of 0.4 kcal/mol to TM complex stability in bicelles. In membranes,
      it proved more difficult to replace tryptophan even by tyrosine, indicating a
      superior capacity to interact with heterogeneous lipids of biological membranes.
      Interestingly, at intracellular TM helix ends, where integrin activation is
      initiated, sequence motifs that interact with lipids via opposing polarity
      patterns were found to restrict TM helix orientations beyond tryptophan
      anchoring. In contrast to bicelles, phenylalanine became the least accepted
      substitute in membranes, demonstrating an increased role of the hydrophobic
      effect. Altogether, our study implicates a wide amphiphilic range of tryptophan,
      membrane complexity, and the hydrophobic effect to be important factors in
      tryptophan membrane anchoring.

PMID- 29323922
TI  - Switchable Single-Mode Perovskite Microlasers Modulated by Responsive Organic
      Microdisks.
AB  - Miniaturized lasers with high spectra purity and switchable output are of crucial
      importance for various ultracompact photonic devices. However, it still remains a
      great challenge to simultaneously control the wavelength and mode purity of
      microscale lasers due to the insensitive response of traditional materials to
      external stimuli. In this work, we propose a strategy to realize switchable
      single-mode microlasers in perovskite microwires (MWs) coupled with responsive
      organic microdisk cavities. The perovskite MW therein serves as an excellent
      laser source to deliver multiple lasing modes, while the microdisk functions as a
      spectral filter to achieve single-mode outcoupling. Furthermore, on account of
      the sensitive responsiveness of organic materials, reversible wavelength
      switching of single-mode laser can be realized through adjusting the resonant
      modes of the microdisk cavity filter. The results will provide guidance for the
      rational design of nanophotonic devices with novel performances based on the
      characteristic of organic materials.

PMID- 29323923
TI  - Dynamic Changes of Intracellular Monomer Levels Regulate Block Sequence of
      Polyhydroxyalkanoates in Engineered Escherichia coli.
AB  - Biological polymer synthetic systems, which utilize no template molecules,
      normally synthesize random copolymers. We report an exception, a synthesis of
      block polyhydroxyalkanoates (PHAs) in an engineered Escherichia coli. Using an
      engineered PHA synthase, block copolymers poly[(R)-2-hydroxybutyrate(2HB)-b-(R)-3
      hydroxybutyrate(3HB)] were produced in E. coli. The covalent linkage between
      P(2HB) and P(3HB) segments was verified with solvent fractionation and microphase
      separation. Notably, the block sequence was generated under the simultaneous
      consumption of two monomer precursors, indicating the existence of a rapid
      monomer switching mechanism during polymerization. Based on in vivo metabolic
      intermediate analysis and the relevant in vitro enzymatic activities, we propose
      a model in which the rapid intracellular 3HB-CoA fluctuation during polymer
      synthesis is a major factor in generating block sequences. The dynamic change of
      intracellular monomer levels is a novel regulatory principle of monomer sequences
      of biopolymers.

PMID- 29323924
TI  - Akt Serine/Threonine Kinase 1 Regulates de Novo Fatty Acid Synthesis through the
      Mammalian Target of Rapamycin/Sterol Regulatory Element Binding Protein 1 Axis in
      Dairy Goat Mammary Epithelial Cells.
AB  - Akt serine/threonine kinase acts as a central mediator in the
      phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway, regulating a series
      of biological processes. In lipid metabolism, Akt activation regulates a series
      of gene expressions, including genes related to intracellular fatty acid
      synthesis. However, the regulatory mechanisms of Akt in dairy goat mammary lipid
      metabolism have not been elaborated. In this study, the coding sequences of goat
      Akt1 gene were cloned and analyzed. Gene expression of Akt1 in different
      lactation stages was also investigated. For in vitro studies, a eukaryotic
      expression vector of Akt1 was constructed and transfected to goat mammary
      epithelial cells (GMECs), and specific inhibitors of Akt/mammalian target of
      rapamycin (mTOR) signaling were applied to GMECs. Results showed that Akt1
      protein was highly conserved, and its mRNA was highly expressed in midlactation.
      In vitro studies indicated that Akt1 phosphorylation activated mTOR and
      subsequently enhanced sterol regulatory element binding protein 1 (SREBP1), thus
      increasing intracellular triacylglycerol content. Inhibition of Akt/mTOR
      signaling down-regulated the gene expression of lipogenic genes. Overall, Akt1
      plays an important role in regulating de novo fatty acid synthesis in goat
      mammary epithelial cells, and this process probably is through the mTOR/SREBP1
      axis.

PMID- 29323925
TI  - The Responsiveness of Patient- Reported Outcome Tools in Shoulder Surgery Is
      Dependent on the Underlying Pathological Condition.
AB  - BACKGROUND: Given the high number of available patient-reported outcome (PRO)
      tools for patients undergoing shoulder surgery, comparative information is
      necessary to determine the most relevant forms to incorporate into clinical
      practice. PURPOSE: To determine the utilization and responsiveness of common PRO
      tools in studies involving patients undergoing arthroscopic rotator cuff repair
      or operative management of glenohumeral instability. STUDY DESIGN: Systematic
      review. METHODS: A systematic review of rotator cuff and instability studies from
      multiple databases was performed according to PRISMA guidelines. Means and SDs of
      each PRO tool utilized, study sample sizes, and follow-up durations were
      collected. The responsiveness of each PRO tool compared with other PRO tools was
      determined by calculating the effect size and relative efficiency (RE). RESULTS:
      After a full-text review of 238 rotator cuff articles and 110 instability
      articles, 81 studies and 29 studies met the criteria for final inclusion,
      respectively. In the rotator cuff studies, 25 different PRO tools were utilized.
      The most commonly utilized PRO tools were the Constant (50 studies), visual
      analog scale (VAS) for pain (44 studies), American Shoulder and Elbow Surgeons
      (ASES; 39 studies), University of California, Los Angeles (UCLA; 20 studies), and
      Disabilities of the Arm, Shoulder and Hand (DASH; 13 studies) scores. The ASES
      score was found to be more responsive than all scores including the Constant (RE,
      1.94), VAS for pain (RE, 1.54), UCLA (RE, 1.46), and DASH (RE, 1.35) scores. In
      the instability studies, 16 different PRO tools were utilized. The most commonly
      used PRO tools were the ASES (13 studies), Rowe (10 studies), Western Ontario
      Shoulder Instability Index (WOSI; 8 studies), VAS for pain (7 studies), UCLA (7
      studies), and Constant (6 studies) scores. The Rowe score was much more
      responsive than both the ASES (RE, 22.84) and the Constant (RE, 33.17) scores;
      however, the ASES score remained more responsive than the Constant (RE, 1.93),
      VAS for pain (RE, 1.75), and WOSI (RE, 0.97) scores. CONCLUSION: Despite being
      frequently used in the research community, the Constant score may be less
      clinically useful as it was less responsive. Additionally, it is a greater burden
      on the provider because it requires objective strength and range of motion data
      to be gathered by the clinician. In contrast, the ASES score was highly
      responsive after rotator cuff repair and requires only subjective patient input.
      Furthermore, separate PRO scoring methods appear to be necessary for patients
      undergoing rotator cuff repair and surgery for instability as the instability
      specific Rowe score was much more responsive than the ASES score.

PMID- 29323926
TI  - Investigating Effects of Sex Differences and Prior Concussions on Symptom
      Reporting and Cognition Among Adolescent Soccer Players.
AB  - BACKGROUND: There has been increasing concern regarding the possible effect of
      multiple concussions on the developing brain, especially for adolescent females.
      Hypothesis/Purpose: The objectives were to determine if there are differences in
      cognitive functioning, symptom reporting, and/or sex effects from prior
      concussions. In a very large sample of youth soccer players, it was hypothesized
      that (1) there would be no differences in cognitive test performance between
      those with and without prior concussions, (2) baseline preseason symptoms would
      be better predicted by noninjury factors than concussion history, and (3) males
      and females with prior concussions would not have differences in cognition or
      symptoms. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS:
      Participants included 9314 youth soccer players (mean = 14.8 years, SD = 1.2) who
      completed preseason baseline cognitive testing, symptom reporting, and a
      health/injury history questionnaire from the ImPACT battery (Immediate Post
      concussion Assessment and Cognitive Testing). On the basis of injury history,
      athletes were grouped by number of prior concussions: 0 (boys, n = 4012; girls, n
      = 3963), 1 (boys, n = 527; girls, n = 457), 2 (boys, n = 130; girls, n = 97), or
      >=3 (boys, n = 73; girls, n = 55). The primary measures were the 4 primary
      cognitive scores and the total symptom ratings from ImPACT. Primary outcomes were
      assessed across injury groups, controlling for age, sex, learning disability,
      attention-deficit/hyperactivity disorder (ADHD), treatment for
      headaches/migraines, substance abuse, and mental health problems. RESULTS:
      Cognitive test performance was not associated with concussion history but was
      associated with sex, age, learning disability, ADHD, and prior mental health
      problems. Greater symptom reporting was more strongly associated with psychiatric
      problems, older age, learning disability, substance abuse, headaches, being
      female, and ADHD than with a history of multiple concussions. Boys and girls did
      not differ on cognitive scores or symptom reporting based on a history of
      concussion. CONCLUSION: In this very large sample of youth soccer players with
      prior concussion, there was no evidence of negative effects on cognition, very
      weak evidence of negative effects on symptom reporting, and no evidence of sex *
      concussion differences in cognition or symptom reporting.

PMID- 29323927
TI  - Pulmonary Fibrous Nodule with Ossifications May Indicate Vascular Ehlers-Danlos
      Syndrome with Missense Mutation in COL3A1.

PMID- 29323930
TI  - The Economic Burden of Asthma in the United States, 2008-2013.
AB  - RATIONALE: Asthma is a chronic disease that affects quality of life, productivity
      at work and school, and healthcare use; and it can result in death. Measuring the
      current economic burden of asthma provides important information on the impact of
      asthma on society. This information can be used to make informed decisions about
      allocation of limited public health resources. OBJECTIVES: In this paper, we
      provide a comprehensive approach to estimating the current prevalence, medical
      costs, cost of absenteeism (missed work and school days), and mortality
      attributable to asthma from a national perspective. In addition, we estimate the
      association of the incremental medical cost of asthma with several important
      factors, including race/ethnicity, education, poverty, and insurance status.
      METHODS: The primary source of data was the 2008-2013 household component of the
      Medical Expenditure Panel Survey. We defined treated asthma as the presence of at
      least one medical or pharmaceutical encounter or claim associated with asthma.
      For the main analysis, we applied two-part regression models to estimate asthma
      related annual per-person incremental medical costs and negative binomial models
      to estimate absenteeism associated with asthma. RESULTS: Of 213,994 people in the
      pooled sample, 10,237 persons had treated asthma (prevalence, 4.8%). The annual
      per-person incremental medical cost of asthma was $3,266 (in 2015 U.S. dollars),
      of which $1,830 was attributable to prescription medication, $640 to office
      visits, $529 to hospitalizations, $176 to hospital-based outpatient visits, and
      $105 to emergency room visits. For certain groups, the per-person incremental
      medical cost of asthma differed from that of the population average, namely
      $2,145 for uninsured persons and $3,581 for those living below the poverty line.
      During 2008-2013, asthma was responsible for $3 billion in losses due to missed
      work and school days, $29 billion due to asthma-related mortality, and $50.3
      billion in medical costs. All combined, the total cost of asthma in the United
      States based on the pooled sample amounted to $81.9 billion in 2013. CONCLUSIONS:
      Asthma places a significant economic burden on the United States, with a total
      cost of asthma, including costs incurred by absenteeism and mortality, of $81.9
      billion in 2013.

PMID- 29323928
TI  - Association between Household Air Pollution Exposure and Chronic Obstructive
      Pulmonary Disease Outcomes in 13 Low- and Middle-Income Country Settings.
AB  - RATIONALE: Forty percent of households worldwide burn biomass fuels for energy,
      which may be the most important contributor to household air pollution.
      OBJECTIVES: To examine the association between household air pollution exposure
      and chronic obstructive pulmonary disease (COPD) outcomes in 13 resource-poor
      settings. METHODS: We analyzed data from 12,396 adult participants living in 13
      resource-poor, population-based settings. Household air pollution exposure was
      defined as using biomass materials as the primary fuel source in the home. We
      used multivariable regressions to assess the relationship between household air
      pollution exposure and COPD outcomes, evaluated for interactions, and conducted
      sensitivity analyses to test the robustness of our findings. MEASUREMENTS AND
      MAIN RESULTS: Average age was 54.9 years (44.2-59.6 yr across settings), 48.5%
      were women (38.3-54.5%), prevalence of household air pollution exposure was 38%
      (0.5-99.6%), and 8.8% (1.7-15.5%) had COPD. Participants with household air
      pollution exposure were 41% more likely to have COPD (adjusted odds ratio, 1.41;
      95% confidence interval, 1.18-1.68) than those without the exposure, and 13.5%
      (6.4-20.6%) of COPD prevalence may be caused by household air pollution exposure,
      compared with 12.4% caused by cigarette smoking. The association between
      household air pollution exposure and COPD was stronger in women (1.70; 1.24-2.32)
      than in men (1.21; 0.92-1.58). CONCLUSIONS: Household air pollution exposure was
      associated with a higher prevalence of COPD, particularly among women, and it is
      likely a leading population-attributable risk factor for COPD in resource-poor
      settings.

PMID- 29323929
TI  - Variation in Cilia Protein Genes and Progression of Lung Disease in Cystic
      Fibrosis.
AB  - RATIONALE: Cystic fibrosis, like primary ciliary dyskinesia, is an autosomal
      recessive disorder characterized by abnormal mucociliary clearance and
      obstructive lung disease. We hypothesized that genes underlying the development
      or function of cilia may modify lung disease severity in persons with cystic
      fibrosis. OBJECTIVES: To test this hypothesis, we compared variants in 93
      candidate genes in both upper and lower tertiles of lung function in a large
      cohort of children and adults with cystic fibrosis with those of a population
      control dataset. METHODS: Variants within candidate genes were tested for
      association using the SKAT-O test, comparing cystic fibrosis cases defined by
      poor (n = 127) or preserved (n = 127) lung function with population controls (n =
      3,269 or 3,148, respectively). Associated variants were then tested for
      association with related phenotypes in independent datasets. RESULTS: Variants in
      DNAH14 and DNAAF3 were associated with poor lung function in cystic fibrosis,
      whereas variants in DNAH14 and DNAH6 were associated with preserved lung function
      in cystic fibrosis. Associations between DNAH14 and lung function were replicated
      in disease-related phenotypes characterized by obstructive lung disease in
      adults. CONCLUSIONS: Genetic variants within DNAH6, DNAH14, and DNAAF3 are
      associated with variation in lung function among persons with cystic fibrosis.

PMID- 29323931
TI  - Esophageal Manometry and Regional Transpulmonary Pressure in Lung Injury.
AB  - RATIONALE: Esophageal manometry is the clinically available method to estimate
      pleural pressure, thus enabling calculation of transpulmonary pressure (Pl).
      However, many concerns make it uncertain in which lung region esophageal
      manometry reflects local Pl. OBJECTIVES: To determine the accuracy of esophageal
      pressure (Pes) and in which regions esophageal manometry reflects pleural
      pressure (Ppl) and Pl; to assess whether lung stress in nondependent regions can
      be estimated at end-inspiration from Pl. METHODS: In lung-injured pigs (n = 6)
      and human cadavers (n = 3), Pes was measured across a range of positive end
      expiratory pressure, together with directly measured Ppl in nondependent and
      dependent pleural regions. All measurements were obtained with minimal
      nonstressed volumes in the pleural sensors and esophageal balloons. Expiratory
      and inspiratory Pl was calculated by subtracting local Ppl or Pes from airway
      pressure; inspiratory Pl was also estimated by subtracting Ppl (calculated from
      chest wall and respiratory system elastance) from the airway plateau pressure.
      MEASUREMENTS AND MAIN RESULTS: In pigs and human cadavers, expiratory and
      inspiratory Pl using Pes closely reflected values in dependent to middle lung
      (adjacent to the esophagus). Inspiratory Pl estimated from elastance ratio
      reflected the directly measured nondependent values. CONCLUSIONS: These data
      support the use of esophageal manometry in acute respiratory distress syndrome.
      Assuming correct calibration, expiratory Pl derived from Pes reflects Pl in
      dependent to middle lung, where atelectasis usually predominates; inspiratory Pl
      estimated from elastance ratio may indicate the highest level of lung stress in
      nondependent "baby" lung, where it is vulnerable to ventilator-induced lung
      injury.

PMID- 29323932
TI  - The effects of breath alcohol concentration on postural control.
AB  - BACKGROUND: Two of the 3 standardized field sobriety tests that U.S. law
      enforcement uses at roadside checks have a postural equilibrium component to
      them. Those tests have been validated to detect impairment caused by blood
      alcohol concentrations (BACs) of 0.08 g/dL or above. Many medical and traffic
      safety associations support a lower limit, and one state, Utah, has passed a law
      to lower the limit to 0.05 g/dL. Many studies have examined the effects of
      alcohol on postural control (of which postural equilibrium is a component), with
      a consensus emerging that impairment is usually found at BACs greater than 0.06
      g/dL. Most of these studies, however, had a relatively small number of subjects,
      usually between 10 and 30. The current study collected data from a much larger
      sample. OBJECTIVE: The objective of this study was to provide additional evidence
      that posture control is negatively affected at BACs greater than 0.06 g/dL or
      breath alcohol concentrations (BrACs) of 0.06 g/210 L. METHOD: This was a between
      subjects study, with BrAC group as the independent variable (5 levels: 0.00,
      0.04, 0.06, 0.08, and 0.10 g/210 L); 4 measures of postural control as the
      dependent variables; and age, height, and weight as the covariates. Posture
      control was measured with a force-sensing platform connected to a computer. The
      feet's center of pressure (CoP) on the platform was recorded and the
      corresponding movement of the body in the anterior-posterior and lateral planes
      was derived. Participants (N = 96) were randomly assigned to one of the BrAC
      groups. Positive BrAC groups were compared to the zero BrAC group. Data were
      examined with hierarchical multiple regression. RESULTS: Adjusted for age,
      height, and weight, the main effect of lateral CoP with eyes open was not
      statistically significant. There was a statistically significant main effect of
      alcohol on anterior-posterior CoP excursion with eyes open and with eyes closed
      and lateral CoP excursion with eyes closed. For all 3 of those variables, only
      BrACs of 0.08 and 0.10 g/210 L produced differences against zero BrAC. Although
      the main effect of alcohol on Lateral CoP Excursion with eyes open was not
      statistically significant, the contrasts between 0 and 0.08 and 0 and 0.10 g/210L
      BrAC were in the hypothesized direction. CONCLUSION: The current study did not
      directly address the issue of whether the sobriety tests are sensitive to BrACs
      of 0.05 g/210 L or above; rather, it provides additional evidence that postural
      control, one of the components of those tests, is relatively unaffected by BrACs
      lower than 0.08 g/210 L. Additional research is needed on the diagnostic
      characteristics of the sobriety tests at BrACs lower than 0.08 g/210 L.

PMID- 29323934
TI  - Safe speed limits for a safe system: The relationship between speed limit and
      fatal crash rate for different crash types.
AB  - OBJECTIVE: The objective of this article is to provide empirical evidence for
      safe speed limits that will meet the objectives of the Safe System by examining
      the relationship between speed limit and injury severity for different crash
      types, using police-reported crash data. METHOD: Police-reported crashes from 2
      Australian jurisdictions were used to calculate a fatal crash rate by speed limit
      and crash type. Example safe speed limits were defined using threshold risk
      levels. RESULTS: A positive exponential relationship between speed limit and
      fatality rate was found. For an example fatality rate threshold of 1 in 100
      crashes it was found that safe speed limits are 40 km/h for pedestrian crashes;
      50 km/h for head-on crashes; 60 km/h for hit fixed object crashes; 80 km/h for
      right angle, right turn, and left road/rollover crashes; and 110 km/h or more for
      rear-end crashes. CONCLUSIONS: The positive exponential relationship between
      speed limit and fatal crash rate is consistent with prior research into speed and
      crash risk. The results indicate that speed zones of 100 km/h or more only meet
      the objectives of the Safe System, with regard to fatal crashes, where all crash
      types except rear-end crashes are exceedingly rare, such as on a high standard
      restricted access highway with a safe roadside design.

PMID- 29323935
TI  - Shape-related characteristics of age-related differences in subcortical
      structures.
AB  - OBJECTIVES: With an increasing aging population, it is important to understand
      biological markers of aging. Subcortical volume is known to differ with age;
      additionally considering shape-related characteristics may provide a better index
      of age-related differences. Fractal dimensionality is more sensitive to age
      related differences, but is borne out of mathematical principles, rather than
      neurobiological relevance. We considered four distinct measures of shape and how
      they relate to aging and fractal dimensionality: surface-to-volume ratio,
      sphericity, long-axis curvature, and surface texture. METHODS: Structural MRIs
      from a combined sample of over 600 healthy adults were used to measure age
      related differences in the structure of the thalamus, putamen, caudate, and
      hippocampus. For each, volume and fractal dimensionality were calculated, as well
      as four distinct shape measures. These measures were examined for their utility
      in explaining age-related variability in brain structure. RESULTS: The four shape
      measures were able to account for 80%-90% of the variance in fractal
      dimensionality. Of the distinct shape measures, surface-to-volume ratio was the
      most sensitive biomarker. CONCLUSION: Though volume is often used to characterize
      inter-individual differences in subcortical structures, our results demonstrate
      that additional measures can be useful complements. Our results indicate that
      shape characteristics are useful biological markers of aging.

PMID- 29323933
TI  - Cardioventilatory Control in Preterm-born Children and the Risk of Obstructive
      Sleep Apnea.
AB  - RATIONALE: The contribution of ventilatory control to the pathogenesis of
      obstructive sleep apnea (OSA) in preterm-born children is unknown. OBJECTIVES: To
      characterize phenotypes of ventilatory control that are associated with the
      presence of OSA in preterm-born children during early childhood. METHODS: Preterm
      and term-born children without comorbid conditions were enrolled. They were
      categorized into an OSA group and a non-OSA group on the basis of
      polysomnography. MEASUREMENTS AND MAIN RESULTS: Loop gain, controller gain, and
      plant gain, reflecting ventilatory instability, chemoreceptor sensitivity, and
      blood gas response to a change in ventilation, respectively, were estimated from
      spontaneous sighs identified during polysomnography. Cardiorespiratory coupling,
      a measure of brainstem maturation, was estimated by measuring the interval
      between inspiration and the preceding electrocardiogram R-wave. Cluster analysis
      was performed to develop phenotypes based on controller gain, plant gain,
      cardiorespiratory coupling, and gestational age. The study included 92 children,
      63 of whom were born preterm (41% OSA) and 29 of whom were born at term (48%
      OSA). Three phenotypes of ventilatory control were derived with risks for OSA
      being 8%, 47%, and 77% in clusters 1, 2, and 3, respectively. There was a
      stepwise decrease in controller gain and an increase in plant gain from clusters
      1 to 3. Children in cluster 1 had significantly higher cardiorespiratory coupling
      and gestational age than clusters 2 and 3. No difference in loop gain was found
      between clusters. CONCLUSIONS: The risk for OSA could be stratified according to
      controller gain, plant gain, cardiorespiratory coupling, and gestational age.
      These findings could guide personalized care for children at risk for OSA.

PMID- 29323936
TI  - Sleep Research: A Primer for Media Scholars.
AB  - The average amount of sleep people of all ages get has declined sharply in the
      past 50 years. The detrimental health effects of sleep deprivation are well
      documented and substantial. Even though electronic media use often takes place in
      the hours before sleep, the extent to which media use may interact with sleep is
      understudied and not well understood. Communication scholars are well positioned
      to contribute to this area, as a systematic, theoretical understanding of the
      relationship between media and sleep is still lacking. This primer charts the
      state of knowledge on electronic media and sleep and explores possible next
      steps. First, we introduce the problem of sleep deprivation and describe the
      basic science of sleep with relevant terminology. Then, we review the research on
      electronic media and sleep and offer an agenda for research.

PMID- 29323938
TI  - Rural Nurse Managers' Perspectives into Better Communication Practices.
AB  - The aim of this qualitative study was to describe the communication perceptions
      of nurse managers in rural areas. Prior research in tertiary settings was the
      impetus for studying viewpoints in other settings. Grounded theory methods were
      used to collect and analyze interview data with nine managers from regional,
      critical access hospitals, and home health settings in central Pennsylvania.
      Nurse Managers associated successful communication with job satisfaction, work
      efficiency, and employee retention. Circumstances influencing communication
      involved discussion tones, techniques, resources, and environmental factors.
      Recommended techniques included regular conversations, diverse messaging, and
      conferencing huddles to improve information dissemination and workflow in rural
      settings.

PMID- 29323939
TI  - Prevalence of Pain and Effects of a Brief Mindfulness-Based Intervention on
      Chinese Community-Dwelling Older Adults with Chronic Pain.
AB  - This study aimed to screen the prevalence of pain in Chinese community-dwelling
      older adults and to evaluate the effects of a brief mindfulness-based
      intervention on chronic pain. The prevalence of pain among Chinese older adults
      was 40.5%. The brief mindfulness intervention had significant effects on reducing
      pain intensity (P = 0.004), and increasing the mindfulness measures: observing,
      acting with awareness, non-judging and non-reactivity inner experience (all P
      values < 0.05). Pain prevalence among Chinese older adults was relatively high.
      This study showed that a brief mindfulness-based intervention reduced ratings of
      pain intensity and enhanced ratings of the perception of mindfulness.

PMID- 29323940
TI  - Elevated Blood Pressure in Low-Income, Rural Preschool Children is Associated
      with Maternal Hypertension during Pregnancy.
AB  - Hypertension (HTN) is a significant public health problem in adults, and rates of
      HTN are rising in children as well. The purpose of this study was to determine
      blood pressure (BP) and body mass index (BMI) levels in low-income, rural
      preschool children and investigate the relationship between child and maternal
      factors that impact BP and BMI in these children. Results indicated high rates of
      overweight/obesity and elevated BP levels in this sample. Maternal hypertension
      during pregnancy also emerged as a predictor of elevated BP in their children.

PMID- 29323941
TI  - Barriers to Health Care Access for Low Income Families: A Review of Literature.
AB  - Having a low-income presents a variety of problems for families and children,
      with access to health care being the most complex and prevalent. Although there
      are many challenges for low-income families to access adequate health care in the
      United States, the key barriers identified in this review of literature are a
      lack of education, complications with health insurance, and a distrust of health
      care providers. Each obstacle is influenced by a myriad of factors that affect
      vulnerable sub-groups of low-income families. Acknowledging the barriers that
      prevent access to health care for low-income families is the first step towards
      determining future sustainable solutions.

PMID- 29323943
TI  - Electronic Media Use and Sleep Among Preschoolers: Evidence for Time-Shifted and
      Less Consolidated Sleep.
AB  - This study examined the association between electronic media use and sleep among
      preschoolers, using a national sample of 402 mothers of 3- to 5-year-olds.
      Participants completed an online survey assessing preschoolers' electronic media
      use, bedtime and wake time, sleep time, napping behaviors, and sleep
      consolidation. Results showed that heavier television use and tablet use, both
      overall and in the evening, were associated with later bedtimes and later wake
      times, but not with fewer hours of sleep, providing evidence for a time-shifting
      process. In addition, heavier daily television use and evening smartphone use
      were associated with increased daytime napping. Moreover, heavier daily
      television use, daily and evening smartphone use, and evening tablet use were
      associated with poorer sleep consolidation, suggesting less mature sleep
      patterns. These findings indicate that media effects on the timing of sleep and
      the proportion of sleep that occurs at night are important to consider when
      assessing the health risks of electronic media on children.

PMID- 29323942
TI  - Comparison of Juvenile Allogenous Articular Cartilage and Bone Marrow Aspirate
      Concentrate Versus Microfracture With and Without Bone Marrow Aspirate
      Concentrate in Arthroscopic Treatment of Talar Osteochondral Lesions.
AB  - BACKGROUND: The purpose of this study was to compare the functional and
      radiographic outcomes of patients who received juvenile allogenic chondrocyte
      implantation with autologous bone marrow aspirate (JACI-BMAC) for treatment of
      talar osteochondral lesions with those of patients who underwent microfracture
      (MF). METHODS: A total of 30 patients who underwent MF and 20 who received DeNovo
      NT for JACI-BMAC treatment between 2006 and 2014 were included. Additionally, 17
      MF patients received supplemental BMAC treatment. Retrospective chart review was
      performed and functional outcomes were assessed pre- and postoperatively using
      the Foot and Ankle Outcome Score and Visual Analog pain scale. Postoperative
      magnetic resonance images were reviewed and evaluated using a modified Magnetic
      Resonance Observation of Cartilage Tissue (MOCART) score. Average follow-up for
      functional outcomes was 30.9 months (range, 12-79 months). Radiographically,
      average follow-up was 28.1 months (range, 12-97 months). RESULTS: Both the MF and
      JACI-BMAC showed significant pre- to postoperative improvements in all Foot and
      Ankle Outcome Score subscales. Visual Analog Scale scores also showed improvement
      in both groups, but only reached a level of statistical significance ( P < .05)
      in the MF group. There were no significant differences in patient reported
      outcomes between groups. Average osteochondral lesion diameter was significantly
      larger in JACI-BMAC patients compared to MF patients, but size difference had no
      significant impact on outcomes. Both groups produced reparative tissue that
      exhibited a fibrocartilage composition. The JACI-BMAC group had more patients
      with hypertrophy exhibited on magnetic resonance imaging (MRI) than the MF group
      ( P = .009). CONCLUSION: JACI-BMAC and MF resulted in improved functional
      outcomes. However, while the majority of patients improved, functional outcomes
      and quality of repair tissue were still not normal. Based on our results, lesions
      repaired with DeNovo NT allograft still appeared fibrocartilaginous on MRI and
      did not result in significant functional gains as compared to MF. LEVEL OF
      EVIDENCE: Level III, comparative series.

PMID- 29323944
TI  - MODIFICATION OF SEA ANEMONE BEHAVIOR BY SYMBIOTIC ZOOXANTHELLAE: PHOTOTAXIS.
AB  - The sea anemone Anthopleura elegantissima, with and without endosymbiotic
      zooxanthellae, was tested for evidence of phototactic behavior. Anemones with
      zooxanthellae always displayed phototaxis, either positive or negative depending
      on the experimental light intensity and the light intensity of the habitat from
      which the animals were taken. Anemones without zooxanthellae-even those that had
      previously harbored zooxanthellae and that were genetically identical clone-mates
      of phototactic individuals-never displayed phototaxis, appearing completely
      indifferent to light and shade. The results indicate that phototaxis in this sea
      anemone depends directly on the presence of its symbiotic algae. It is suggested
      that the flexible phototactic behavior of the anemone may play an important role
      in favorably regulating the amount of light to which the zooxanthellae are
      exposed.

PMID- 29323945
TI  - ULTRASTRUCTURE OF A CEPHALOPOD PHOTOPHORE. I. STRUCTURE OF THE PHOTOGENIC TISSUE.
AB  - One type of photophore of the deep sea squid Pterygioteuthis microlampas was
      examined with the electron microscope and its fine structure described. The
      photogenic tissue is composed of four cell types each with distinctive morphology
      which suggests their function. The photocytes branch and ramify throughout the
      central region of the photophore and have an extensive system of microvilli (the
      photogenic organelle) which are arranged about a central blood filled lumen. The
      photocytes apparently develop inside a sheath cell and are surrounded by a sheath
      which is continuous with the basement membrane of the blood vessels. The
      photocytes and associated sheath cells are surrounded by packing cells whose
      cytoplasm is replaced with a homogeneous granular material. Finally, cells
      containing many mitochondria branch and ramify throughout the photogenic area.
      Apparently the circulatory system is in direct contact with the photocytes, and
      acellular blood vessels, composed only of basement membrane, are found throughout
      the photogenic tissue. The similarity between photoproductive organelles and
      photoreceptive organelles is striking.

PMID- 29323946
TI  - MODIFICATION OF SEA ANEMONE BEHAVIOR BY SYMBIOTIC ZOOXANTHELLAE: EXPANSION AND
      CONTRACTION.
AB  - The pattern of expansion and contraction by the sea anemone Anthopleura
      elegantissima differs in individuals with or without endosymbiotic zooxanthellae.
      Anemones without zooxanthellae, found in dark habitats, do not regularly expand
      or contract under changes in light. Anemones with zooxanthellae expand in
      moderate light and contract in intense light or in darkness, with striking
      uniformity. However, this behavior does not always depend directly on the
      presence of zooxanthellae. Anemones that have previously had endosymbiotic
      zooxanthellae subsequently expand and contract with changes in light in the
      absence of these algae. Thus, conditioned responses may be involved. It is
      suggested that expansion and contraction of the anemones may play an important
      role in favorably regulating the amount of light to which their zooxanthellae are
      exposed.

PMID- 29323947
TI  - ULTRASTRUCTURE OF A CEPHALOPOD PHOTOPHORE. II. IRIDOPHORES AS REFLECTORS AND
      TRANSMITTERS.
AB  - The iridophores of one type of photophore of the deep sea squid, Pterygioteuthis
      microlampas were examined with the electron microscope and four different types
      were found. Three of these types have not been previously described. The regular
      iridophores of the posterior cup appear to be one-fourth wave length reflectors
      and redirect the light produced by the photogenic tissue outward. The regular
      iridophores of the anterior cap have a different spacing and platelet thickness
      so they apparently pass blue light. The irregular iridophores form a cone around
      the photogenic tissue and probably randomly reflect light back into the
      photogenic tissue. The iridophores of the lens have many precisely aligned
      iridosomes with platelet spacing and thickness so that they appear to collimate
      light passing through them. It appears that these three types of iridophores
      reflect, transmit and collimate the light produced in the photophore to match the
      background illumination hence making an efficient countershading mechanism. A
      fourth type of iridophore, the wide spaced iridophore, is rarely encountered and
      probably does not have a significant role in light attenuation in the photophore.

PMID- 29323948
TI  - SOME CONSEQUENCES OF SEXUAL DIMORPHISM: FEEDING IN MALE AND FEMALE FIDDLER CRABS,
      UCA PUGNAX (SMITH).
AB  - 1. There were no differences in the respiratory rates of male and female Uca
      pugnax of comparable sizes. 2. The amount of salt marsh sediment ingested by
      starved male and female crabs was similar. 3. The number and weight of fecal
      pellets produced by male and female crabs were similar, as was the organic matter
      content. 4. The above suggests that there are minimal differences in food demands
      and digestive efficiencies between the sexes, yet the enlarged claw of the
      fiddler crabs cannot be used for feeding. This requires some compensatory
      mechanism in male crabs. 5. Male fiddlers do show about half the feeding motions
      per unit time compared to females, but they compensate by feeding about twice as
      long. This is corroborated by field observations. 6. Further compensation, if
      needed, could be achieved by the slightly larger holding surface of the feeding
      claw in males, perhaps allowing the grasping of larger fragments of marsh
      sediment.

PMID- 29323949
TI  - STUDIES ON THE REPRODUCTIVE SYSTEMS OF SEA-STARS. I. THE MORPHOLOGY AND HISTOLOGY
      OF THE GONAD OF ASTERIAS VULGARIS.
AB  - The results reported here provide a detailed account of the general morphology
      and histology of the male and female gonads of the sea-star Asterias vulgaris.
      The reproductive system of this sea-star (normal five-rayed specimens) consists
      of 10 separate units, each located proximally on the lateral wall of the ray, one
      on either side of the ray. Each unit is composed of a gonad, a gonoduct, and
      genital branches of the aboral haemal and coelomic rings. The gonad is a single
      bag-like structure with several protrusions (termed major and minor acini)
      extending from its surface. Its wall is composed of two sacs, one inside the
      other, separated by the genital coelomic (perihaemal) sinus. The outer sac
      consists of visceral peritoneum, an elastic-collagenous connective tissue layer,
      and many epithelial cells and circular muscle fibers. The inner sac comprises
      epithelial cells and longitudinal muscle fibers, the haemal sinus and contents,
      and germinal epithelium. The haemal sinus includes the haemal sinus space, filled
      with granular haemal fluid, cells, and collagen and other fine fibers enclosed by
      two fibrous laminae. Significant modifications in the form of the gonad and in
      the condition and relationships of the tissues which compose it occur during the
      annual reproductive cycle. Both sacs are stretched during growth of the gonad,
      the outer layers becoming attenuated and the inner layers being pressed against
      the outer, often obliterating the genital coelomic (perihaemal) sinus. The inner
      group of tissues is often extensively folded, pushing ridges formed from the
      inner wall of the haemal sinus and germinal epithelium into the lumen of the
      gonad. It is pointed out that previous studies on the gonads of asteroids have
      been relatively few, with no study for any species dealing comprehensively with
      morphological and histological details of the gonad based on both light and
      electron microscopy. Comparison of the results of the present study with
      observations of previous investigators indicates that although significant
      differences occur (especially in morphological terms), the general features of
      the histology of the wall of the gonad of many sea-stars are similar. In order to
      broaden our base for comparative studies, and to pursue significant problems,
      morphological, histological, histochemical, and ultrastructural investigations
      should be extended to as many asteroid species as possible.

PMID- 29323950
TI  - FEEDING OF OVALIPES GUADULPENSIS (SAUSSURE) (DECAPODA: BRACHYURA: PORTUNIDAE),
      AND MORPHOLOGICAL ADAPTATIONS TO A BURROWING EXISTENCE.

PMID- 29323951
TI  - THE OCCURRENCE, DISTRIBUTION AND ATTACHMENT OF THE PEDUNCULATE BARNACLE
      OCTOLASMIS MULLERI (COKER) ON THE GILLS OF CRABS, PARTICULARLY THE BLUE CRAB.
      CALLINECTES SAPIDUS RATHBUN.
AB  - 1. O. mulleri was present on the gills of most crab species in Beaufort Inlet but
      not on C. sapidus further upriver indicating that salinity is probably a factor
      controlling the incidence of the barnacle. 2. The distribution of the barnacle on
      the individual gills of C. sapidus has been analyzed and the factors affecting
      this distribution discussed. The main factors are the cleaning action of the
      epipodites and the respiratory flow of the crab. 3. The barnacle settlement stage
      larva (cyprid) attaches to blue crab gills a short distance in from the gill
      margin. The orientation of the larva at settlement is a response to the
      respiratory flow of the crab resulting in the cirral net of the young barnacle
      facing into the current. 4. The cement apparatus and internal stalk structures of
      O. mulleri and Lepas anatifera are compared.

PMID- 29323952
TI  - LARVAL SETTLEMENT OF A SYMBIOTIC HYDROID: SPECIFICITY AND NEMATOCYST RESPONSES IN
      PLANULAE OF PROBOSCIDACTYLA FLAVICIRRATA.
AB  - Planulae of the symbiotic hydroid Proboscidactyla flavicirrata settle on the rims
      of sabellid tubes by adhering sequentially and specifically to two different
      substrates. For both steps, nematocysts are the agents of adhesion. Although the
      cnidoblasts of these planulae require local excitation, they are subject to
      endogenous controls. Upon being swept into the plumes of tentacular cirri that
      sabellids extend from their tubes, planulae attach to individual pinnules
      (branches of the tentacular cirri) by discharging nematocysts. Within 2 min
      following attachment, the planulae cease discharging nematocysts in response to
      additional pinnule contacts. Planulae transfer to the rims of sabellid tubes by
      adhering with nematocysts when the sabellids retract their plumes. Cnidoblasts of
      planulae only become responsive to contact with sabellid tube after 4 min or more
      of continuous attachment to pinnules. Transfer initiates metamorphosis. Planulae
      are capable of settling and metamorphosing on Eudistylia vancouveri, a sabellid
      species that is sympatric with the normal hosts of Proboscidactyla, but will not
      support colonies. Apparently the deficiencies of Eudistylia as a host are
      manifested only after planula metamorphosis.

PMID- 29323953
TI  - WATER TRANSPORT RATES OF THE TUNICATE CIONA INTESTINALIS.
AB  - Sea water transport rates of the tunicate Ciona intestinalis were determined by
      measuring the volume of sea water transported through the specimen, and measuring
      the number of particles cleared by the specimen in a given time interval. The
      rate was also determined directly by matching the flow produced by the tunicate
      to that produced by a calibrated pump. Ciona transports sea water at variable
      rates; at times, it does not transport at all. The rate limits covering all
      techniques are: lower limit, 2.5 ml/hr/g wet weight and upper limit, 185 ml/hr/g
      wet weight; the average value based on clearance and direct measurements is 50
      ml/ hr/g wet weight. Even at the lowest rate found, transport is rapid enough to
      ensure complete mixing between sea water and reaction or absorption sites in the
      pharyngeal chamber, alimentary tract or atrial chamber. We conclude that the rate
      controlling process for absorption of oxygen, vanadate ions, micro-organisms or
      organic detritus is not the rate of passage of the feeding current, but rather
      the rate of the intrinsic absorption process such as complex formation, ion
      exchange or adsorption.

PMID- 29323954
TI  - DEVELOPMENT OF THE EOLID NUDIBRANCH CUTHONA NANA (ALDER AND HANCOCK, 1842), AND
      ITS RELATIONSHIP WITH A HYDROID AND HERMIT CRAB.
AB  - 1. The larval development, metamorphosis, and postlarval growth of the eolid
      nudibranch, Cuthona nana, is described. Hatching occurred within 19 days at 11-13
      degrees  C. The lecithotrophic veligers remained nonpelagic and proceeded to
      metamorphose within another two days. 2. Adult nutrition did not affect egg size
      or subsequent development and metamorphosis. 3. Embryogenesis, hatching, and
      metamorphosis were unaffected by the presence or absence of the adult
      nudibranch's prey, the hydroid Hydractinia echinata. 4. Different temperatures
      altered the rate of development and of metamorphosis but not the type of
      development. Egg masses collected in the field and incubated at the temperature
      at which they were collected invariably produced nonpelagic lecithotrophic
      veligers which then metamorphosed. 5. Newly metamorphosed specimens of C. nana
      survived for up to six weeks at 11-13 degrees  C and ten weeks at 4 degrees  C in
      the absence of H. echinata. 6. In the presence of abundant food, specimens of C.
      nana deposited fertile egg masses within 11 weeks after metamorphosis at 11-13
      degrees  C, and continued feeding and ovipositing for two months. 7. Cuthona nana
      feeds specifically on Hydractinia echinata, which in Gosport Harbor is found
      predominantly on shells occupied by Pagurus acadianus. As the hermit crabs move
      about, postlarvae of C. nana are swept up by the gastrozooids of H. echinata, are
      not eaten by the polyps but reorient and feed on hydroid tissue. 8. Nonpelagic
      development in C. nana appears to result in a patchy distribution of postlarvae
      on the bottom, and an uneven, nonrandom distribution of young nudibranchs on the
      H. echinata colonies. 9. Cuthona nana does not kill the H. echinata colonies it
      preys upon, but only crops some of the polyps before leaving the colony to find a
      mate or deposit eggs. Lost polyps are subsequently regenerated.

PMID- 29323955
TI  - STUDIES ON FUNCTIONAL MORPHOLOGY IN THE DIGESTIVE SYSTEM OF OREASTER RETICULATUS
      (L.) (ASTEROIDEA).
AB  - This paper presents, with illustrations, a description of the digestive system of
      Oreaster reticulatus, a species for which such anatomical details have hitherto
      been unavailable. Special features of the digestive system include a large,
      highly eversible cardiac stomach with a particularly well-developed system of
      securing and retracting fibers; a highly specialized pyloric stomach giving rise
      to paired pyloric caeca, each of which is associated with an unusually elaborate
      Tiedemann's pouch featuring a series of secondary pouches branching off along its
      length; and a set of very voluminous intestinal caeca. By comparison with other
      asteroids for which anatomical details and feeding biology are known (especially
      Patiria miniata and Porania pulvillus), it is suggested that O. reticulatus is
      equipped for a variety of modes of feeding. The cardiac stomach is well adapted
      for the digestion of large pieces of food outside the body; it may also function
      as a flagellary-mucous particle-collector, as the similar organ of Patiria is
      thought to do. The specializations of the upper part of the digestive system are
      closely similar to corresponding organs in the known particle-feeding species
      Porania pulvillus, and it seems probable that Oreaster may use its Tiedemann's
      pouches and intestinal caeca to bring particle-laden water into the digestive
      system in a manner similar to that described for Porania. Such direct
      observations as are available on the feeding behavior of O. reticulatus tend to
      confirm the conclusions inferred on indirect, anatomical grounds.

PMID- 29323956
TI  - INTERACTION OF IONIZED AND UN-IONIZED AMMONIA ON SHORT-TERM SURVIVAL AND GROWTH
      OF PRAWN LARVAE, MACROBRACHIUM ROSENBERGH.
AB  - 1. The toxicity of ammonia to Macrobrachium larvae was tested at pH 6.83, 7.60,
      and 8.34, and the respective 144 hr LC50 values were 80, 44, and 14 mg
      ammonia/liter. 2. Toxicity of ammonia was not due solely to the NH3 molecule. In
      solutions of different pH and equal NH3 concentrations, survival was greatly
      reduced as NH4+ levels increased. 3. A model is proposed to explain the
      differential effect of ammonia as pH varies. At higher pH (8.4) toxicity results
      from copious diffusion of NH3 into larvae. At lower pH (6.8) toxicity is thought
      to result from competitive inhibition of Na+ transport by NH4+. 4. Retardation of
      growth was documented in sublethal concentrations of ammonia at 6.8 and 7.6. The
      average dry weight was about 26% less than that of controls (P < 0.05) after a
      seven day exposure. 5. Results are discussed relevant to the culture and
      maintenance of crustaceans, and it is concluded that ammonia will not pose a
      substantial threat in adequately managed systems.

PMID- 29323957
TI  - DESCRIPTIONS OF THE LARVAE OF STICHASTER AUSTRALIS (VERRILL) AND COSCINASTERIAS
      CALAMARIA (GRAY) (ECHINODERMATA: ASTEROIDEA) FROM NEW ZEALAND, OBTAINED FROM
      LABORATORY CULTURE.
AB  - 1. Methods for the laboratory rearing of larvae of the starfishes Stichaster
      australis and Coscinasterias calamaria are described. 2. Larval development in S.
      australis and C. calamaria is very similar, although C. calamaria has a slightly
      faster rate of development. Fertilized eggs develop through a bipinnaria to a
      brachiolaria stage. Late brachiolaria larvae were present 38 days after
      fertilization in S. australis and 27 days after fertilization in C. calamaria. 3.
      As in the development of the feeding larvae, the process of metamorphosis is very
      similar in S. australis and C. calamaria. The time from attachment to the
      substratum by the late brachiolaria larvae to the completion of metamorphosis of
      the juvenile starfish is 6-7 days in S. australis and 6 days in C. calamaria. 4.
      Unfavorable culture conditions may have been the cause of abnormal larvae found
      in some cultures. 5. Larval development of S. australis and C. calamaria
      resembles closely that of other starfish species with indirect development,
      especially Asterias rubens. This may reflect the close taxonomic affinities of
      these three species.

PMID- 29323958
TI  - BIPHASIC PARTICULATE MEDIA FOR THE CULTURE OF FILTER-FEEDERS.
AB  - 1. Over 200 parthenogenetic generations of the freshwater Cladocera Moina
      macrocopa were obtained aseptically in three artificial media. 2. The media have
      two phases: a liquid phase supplying mineral salts, water soluble vitamins,
      nucleic acids, and a liver extract and a fine particulate phase made from
      coagulated proteins, starch and lipid factors. 3. The particulate phase supplies
      the bulk nutrients very efficiently; hence, this type of media may be useful for
      growing other filter-feeders.

PMID- 29323959
TI  - DEVELOPMENT OF THE DIMORPHIC CLAW CLOSER MUSCLES OF THE LOBSTER HOMARUS
      AMERICANUS. III. TRANSFORMATION TO DIMORPHIC MUSCLES IN JUVENILES.
AB  - 1. The two chelipeds of the adult lobster are asymmetrical with respect to their
      external morphology, neuromuscular physiology and utilization in behavior;
      however, they are not genetically fixed in terms of placement or handedness. 2.
      The differentiation of muscle fiber types was studied in the cutter and crusher
      claw closer muscles in the early juvenile stages of the lobster Homarus
      americanus. Muscle fibers were characterized on the basis of sarcomere length. 3.
      In contrast to the adult lobster, where the claw closer muscles are asymmetric,
      the closer muscles of the stage 4 lobster are nearly symmetric; both short and
      long sarcomere muscle fibers are present in each claw and both fiber types have
      an identical regional distribution within the closer muscle. 4. By stage 6 one of
      the muscles differentiates into a cutter muscle with over 60% short sarcomere
      fibers and a distinct regional distribution of short and long sarcomere fibers.
      The other claw closer muscle slowly loses its short sarcomere muscle fibers and
      is transformed into a crusher claw, usually by stage 13-15. 5. The change of the
      closer muscles from a symmetric to an asymmetric condition is correlated with the
      loss in ability for the claws to undergo a "reversal" rather than with the
      external appearance of the claw which becomes differentiated several molts later.

PMID- 29323960
TI  - THE ANNUAL REPRODUCTIVE CYCLE OF AN APODOUS HOLOTHURIAN, LEPTOSYNAPTA TENUIS: A
      BIMODAL BREEDING SEASON.
AB  - 1. Gonads of Leptosynapta tenuis were examined histologically, and gametogenesis
      in this apodid holothurian is described. 2. L. tenuis is a simultaneous
      hermaphrodite. Each animal produces and sheds spermatozoa and oocytes during the
      same breeding season, although sperm seem to be shed somewhat earlier than
      oocytes. 3. Testicular maturity indices and oocyte diameter measurements revealed
      a bimodal annual reproductive cycle in a North Carolina population sampled at
      monthly intervals over a fifteen-month period. Breeding occurred for about three
      months both preceding and following a month, or so, of breeding inactivity in
      July or August. 4. The mid-summer absence of mature gametes in the population
      coincided with the highest seawater temperatures, suggesting a temperature
      regulated gametogenic cycle. 5. The high oocyte growth rate leading to the second
      spawning season in the autumn is perhaps five times that of the winter rate.

PMID- 29323961
TI  - DEVELOPMENT OF AMPHIOPLUS ABDITUS (VERRILL) (ECHINODERMATA: OPHIUROIDEA). II.
      DESCRIPTION AND DISCUSSION OF OPHIUROID SKELETAL ONTOGENY AND HOMOLOGIES.
AB  - 1. Amphioplus abditus has a vestigial two-piece larval skeleton that has portions
      with different crystallographic orientations. The larval skeleton is resorbed
      and, unlike that of echinoids, it does not act as a center of formation of the
      plates of the adult. The major skeletal elements of the adult develop from single
      (usually triradiate) spicules, and there is a uniform crystallographic
      orientation within each plate. 2. The radial shields, adoral shields, genital
      plates and genital scales are ophiuroid specializations without homologues in the
      asteroids. Ophiuroids can regenerate radial shields but not the apical primary
      plates (the latter are probably atavistic structures). 3. The madreporite and
      oral plates, generally thought to migrate from the dorsal surface of the disc,
      originate in situ on the ventral surface of A. abditus. A dorsolateral plate,
      probably confused with the madreporite in past studies, is a precociously formed
      interradial-1. The formation of a "precocious interradial plate" could be a
      vestige of the primitive ophiuroid madreporite. In fact, the madreporites of
      asteroids, ancient ophiuroids, and recent ophuroids may not be homologous. 4. The
      origin of each of the oral papillae is described. Buccal scales, previously (and
      incorrectly) thought to develop into peristomial plates, form the second oral
      papillae in A. abditus. Consequently, the second oral papillae of amphiurids
      should not be considered "oral tentacle scales". The true tentacle scales are
      cryptic structures within the buccal cavity. 5. The oral papillae of the
      different amphiurid genera are probably homologous. Judging from differences in
      the oral frame, there are probably two major amphiurid groups composed of taxa
      which retain the buccal scales as oral papillae (Amphioplus and possibly
      Amphiura), and those like Axiognathus (and possibly Amphipholis and Amphiodia)
      which resorb the buccal scales. 6. A new system of homologues is suggested for
      the plates of the ophiuroid oral skeleton. The proximal oral plate is considered
      the ambulacral portion of the first modified arm-segment and buccal scales may be
      the first pair of adambulacrals. The distal oral plates (ambulacral), adoral
      shields (adambulacral), and the first ventral arm-plate (within the buccal slit)
      compose the second transformed arm-segment of the oral frame. This pattern of
      homology, together with the dissimilarities between ophiuroid and asteroid discs
      constitute important differences between the ophiuroids and asteroids.

PMID- 29323962
TI  - A GENERIC REVISION OF THE BRACKISH-WATER SERPULID FICOPOMATUS SOUTHERN 1921
      (POLYCHAETA: SERPULINAE), INCLUDING MERCIERELLA FAUVEL 1923, SPHAEROPOMATUS
      TREADWELL 1934, MERCIERELLOPSIS RIOJA 1945 AND NEOPOMATUS PILLAI 1960.
AB  - The brackish water serpulid genera Mercierella, Mercierellopsis, Neopomatus and
      Sphaeropomatus are synonymized with Ficopomatus, including four species: F.
      enigmaticus, F. macrodon, F. miamiensis and F. uschakovi. The geographical
      distributions of the species are illustrated, and the confused identity of
      tropical specimens has been clarified, at least in part. The generic position of
      Ficopomatus capensis is discussed. Fossil records of Mercierella and related
      genera most probably do not belong to the genus Ficopomatus.

PMID- 29323963
TI  - LIFE CYCLE, DISTRIBUTION AND ABUNDANCE OF CARCINONEMERTES EPIALTI, A NEMERTEAN
      EGG PREDATOR OF THE SHORE CRAB, HEMIGRAPSUS OREGONENSIS, IN RELATION TO HOST
      SIZE, REPRODUCTION AND MOLT CYCLE.
AB  - 1. The geographic range of Carcinonemertes epialti has been greatly extended. The
      worms are found from Bahia San Quintin, Baja California, Mexico, to Page's
      Lagoon, Vancouver Island, British Columbia, Canada. 2. New host records for C.
      epialti include H. oregonensis, and H. nudus. It is rare on its type host
      Pugettia producta. Specimens of Carcinonemertes of uncertain affinities are also
      found on Cancer antennarius, C. anthonyi and C. productus. 3. Carcinonemertes
      epialti adults are egg predators on ovigerous hosts. Growth, demography and
      abundance are described in relation to the embryogenic stage of the host brood at
      Bodega Harbor, California. 4. Nonfeeding juveniles are ensheathed on individuals
      of both host sexes over 8.0 mm carapace width. 5. Transmission experiments show
      that contact transfer of juvenile nemerteans from males to other hosts may occur.
      6. The percentage of infestation and mean density peak in autumn on H.
      oregonensis at Bodega Harbor. 7. Ovigerous female hosts are more frequently
      infested with C. epialti, particularly at small host sizes, than are male or
      nonovigerous female hosts at Bodega Harbor. However, average worm density on
      ovigerous females is low. 8. Mean density of C. epialti rises through late
      postmolt, declines during intermolt and rebuilds to a high level in late premolt
      H. oregonensisfrom Bodega Harbor. 9. Large crabs have a higher percentage of
      infestations and mean densities per infection than do small crabs. Nemerteans are
      more frequently found in the sternal-abdominal furrow and less frequently in the
      limb axillae on large crabs. 10. A model of C. epialti transmission and site
      occupancy is proposed, incorporating the influence of host size, sex,
      reproductive state, embryogenesis, molt cycle stage and molt cycle duration of H.
      oregonensis at Bodega Harbor. Site availability increases with host size. At
      higher densities the juvenile nemerteans increasingly occupy less preferred
      sites. Transferral of juvenile nemerteans occurs and is considered responsible
      for the high frequency of low infestation levels. Ovigerous females are more
      likely to be infested but with low density infestations.

PMID- 29323964
TI  - THE EFFECT OF pH ON OXYGEN CONSUMPTION AND ACTIVITY IN THE BATHYPELAGIC MYSID
      GNATHOPHAUSIA INGENS.
AB  - 1. Pleopod beat of G. ingens was unaffected by pH at pH 7.1 and pH 7.9 but was
      lower at pH 8.7 due to increased cleaning activity. 2. The relationship between
      oxygen consumption rate, and pleopod beat was found to be semi-logarithmic. 3.
      The relationship between oxygen consumption rate and activity was unaffected by
      pH in the range of pH 7.1 and pH 8.7. 4. The per cent O2 extraction of oxygen by
      G. ingens was not statistically different at pH 7.9 and pH 8.7, but was greater
      at pH 7.1. 5. The ability of G. ingens to regulate its oxygen consumption was
      unaffected by pH in the range studied. 6. Since the increase in per cent O2
      extraction at pH 7.1 does not improve the ability of G. ingens to regulate its
      oxygen uptake, it appears that there is a loss in effectiveness elsewhere in its
      respiratory system at this pH.

PMID- 29323965
TI  - BIOMECHANICS OF WATER-PUMPING BY CHAETOPTERUS VARIOPEDATUS RENIER.
      SKELETOMUSCULATURE AND KINEMATICS.
AB  - 1. The skeletomusculature of the water-pumping segments of Chaetopterus
      variopedatus was examined in detail and the behavior of the segments during
      active water-propulsion was analyzed using cinemaphotographic techniques. 2. The
      musculature of the pumping segments consists largely of thin sheets of radial,
      transverse, and circular fibers, located immediately beneath the thin integument.
      Exceptions to this are the numerous isolated fibers running axially across the
      coelomic cavity of the parapodial rim and the major remotor muscles which
      originate in the neuropodial "sucker" of the adjacent posterior segment. 3. The
      motion of the pump segments is basically reciprocative, with the axial
      displacement during power and recovery strokes approximating a sine function.
      Centrifugal radial displacements (during the power stroke) effectively seal the
      lumen of the tube; centripital radial displacements (during the recovery stroke)
      allow water from the inlet side of the tube to by-pass the pump segment. 4.
      Comparison of the muscle anatomy with the displacements and shape changes which
      take place during water-propulsion permitted analysis of the muscle actions
      during the pump cycle. It is concluded that: (a) both axial and radial
      displacements during the power stroke are caused by a single set of muscles
      (remotors); (b) maintenance of the extended-disk configuration is consequent upon
      coelomic fluid being forced into the parapodial rim, with the axial muscle fibers
      acting as guy-wires to resist overexpansion; (c) most of the sheet-like muscle
      groups contract during the recovery stroke, thereby causing the segment to assume
      a nearly spherical configuration; and (d) two sets of muscles (promotors, oblique
      parapodial) are responsible for the axial displacement during recovery. 5. The
      water-pumping mechanism of Chaetopterus is compared to those of the majority of
      worms, which are based on persistaltic or undulatory movements.

PMID- 29323966
TI  - REAPPRAISAL OF PROCTODONE INVOLVEMENT IN THE HORMONAL REGULATION OF LARVAL
      DIAPAUSE.
AB  - 1. No evidence was found that the larval ileum of the corn boners, Diatraea
      grandiosella and Ostrinia nubilalis, secretes a developmental hormone,
      "proctodone." 2. An abdominal ligature which isolated the ileum of diapause
      larvae of both species caused high mortality but did not retard the pupation
      rate. 3. Extracts prepared from the ileal epithelium of mature nondiapause larvae
      of D. grandiosella were injected into diapause larvae and did not cause premature
      diapause termination. 4. Marked cytological changes occurred in the ileum at the
      onset of metamorphosis. At times the ileal epithelium of both species displayed
      auto and acridine orange-induced fluorescence, characteristic of lysosomes. 5. An
      electron microscopic examination of the autofluorescent ileal epithelium of D.
      grandiosella revealed organelles which had typical lysosomal features and stained
      positively for acid phosphatase activity. 6. The secretory activity of the ileum
      can be accounted for by lysosomal involvement in its metamorphic reorganization,
      and by its osmoregulatory functions.

PMID- 29323967
TI  - COLCHICINE, CYTOCHALASIN B, AND PIGMENT MOVEMENTS IN OVARIAN AND INTEGUMENTARY
      ERYTHROPHORES OF THE PRAWN, PALAEMONETES VULGARIS.
AB  - 1. The effects of colchicine and cytochalasin B on pigment migration in
      integumentary erythrophores of the prawn, Palaemonetes vulgaris, were determined.
      2. Colchicine in a concentration of 25 mM inhibited responses to both the red
      pigment-concentrating and red pigment-dispersing hormones by the integumentary
      erythrophores. Colchicine at a concentration of 5 mM did not inhibit the
      responses of these chromatophores to these hormones. 3. Cytochalasin B (10 ug/ml)
      also inhibited both centrifugal and centripetal migrations of the pigment
      granules in these integumentary enythrophores. 4. Colchicine in a 25 mM solution
      almost completely inhibited the response to red pigment-concentrating hormone in
      ovarian erythrophores whereas 1 mM colchicine produced only a slight inhibition
      of this response. 5. The integumentary erythrophores of Palaemonetes vulgaris are
      the first chromatophores that have been observed in any animal where both pigment
      dispersion and aggregation are inhibited by either colchicine or cytochalasin B.
      6. These results are discussed in relation to previously published data from this
      and other laboratories.

PMID- 29323968
TI  - PIGMENTATION IN THE ORANGE TUNICATE, ECTEINASCIDIA TURBINATA.
AB  - Some chemical properties of the orange pigment from eggs and embryos and the
      mantle tissue of adult Ecteinascidia turbinata, as well as ultrastructural
      characteristics of pigment masses in the mantle, have been examined. The diffuse
      egg and embryo pigment has solubility and absorbence characteristics of
      carotenoids, which are solubilized within yolk platelets. The granular mantle
      pigment, however, is not carotenoid. It is soluble only in organic-aqueous
      systems, stable to boiling and gross changes in pH, and absorbs strongly in the
      UV region with a single major peak at 360 nm. Mantle pigment is found in pigment
      bodies which ultrastructurally are composed of apparently straight and continuous
      tubular subunits, approximately 500 to 600 A in diameter, and oriented parallel
      to the long axis of the body. The pigment bodies are not localized in obvious
      cells but found within large areas of fibrillar material that are bound by
      cytoplasmic membranes and occasionally contain an apparently degenerate nucleus.
      It may be that mantle pigment is derived from pigment cells of the blood which
      lose their typical cellular appearance as they become permanent features of the
      mantle tissue.

PMID- 29323969
TI  - LARVAL DEVELOPMENT AND HABITS OF LAEONEREIS CULVERI (WEBSTER) (POLYCHAETA:
      NEREIDAE).
AB  - The nereid polychaete Laeonereis culveri (Webster) reproduces in the atokal
      condition in the Mystic River Estuary, Connecticut. Females spawn demersal eggs,
      135-162 u in diameter, that do not extrude a jelly layer upon fertilization and
      that give rise to unciliated embryos. Embryogenesis leads directly to a 3-setigen
      larva in four days (at 22 +/- 3 degrees  C; 300/00). The trochophore is
      suppressed due to the retarded development of locomotory cilia which do not
      appear until the 3-setiger larva has formed. Although provided with ciliary
      tracts and capable of swimming, L. culveri larvae are normally benthic in habit.
      They reside in burrows within the upper 2 cm of fine, flocculent sediments where
      they feed chiefly on benthic diatoms until developing past the 5-setiger stage
      after which they become non-selective deposit feeders. The primary function of
      the larval ciliature is to pass water currents through the burrow. In the
      laboratory, 3-to 5-setiger larvae alternately swim and crawl in the absence of
      sediments on in the presence of coarse sediments (particle diameters > 250 u);
      but they readily burrow into and remain within fine sediments (particle diameters
      < 250 u) even if the latter are relatively free of organic matter. Swim-crawl
      behavior also appears to be elicited under conditions of unfavorable water
      quality. When the sixth setiger forms, the larva is no longer capable of swimming
      by means of its cilia. Development beyond the 3-setger stage approximates that of
      other species except that L. culveri larvae are apparently unique in ultimately
      developing eight nototrochs (one per each of the first eight trunk segments). The
      nototrochs are retained and function in burrow ventilation until the 16-to 18
      setiger stages when body undulations commence creating ventilation currents.
      Larval development is completed with addition of the eighth trunk segment. At
      this stage, the tentacular segment (first trunk segment) is incorporated into the
      peristomium and the first pair of parapodia are modified to form the
      posterodorsal tentacular cirri. Sigmoid growth curves resulted when either length
      or segment-formation was used as an indicator of growth among laboratory-reared
      worms. Sexually mature, laboratory-reared worms were only about one-half the
      length of sexually mature worms in a natural population. Thirty-two individuals
      (17 females, 15 males) of an F1 generation were reared to maturity and spawned
      after 168-198 days of development. F2 generation larvae were identical in
      morphology to those of the F1 generation.

PMID- 29323970
TI  - THE MARINE BIOLOGICAL LABORATORY.

PMID- 29323971
TI  - AN ANALYSIS OF SHELL OCCUPATION BY TWO SYMPATRIC SPECIES OF HERMIT CRAB. I.
      ECOLOGICAL FACTORS.
AB  - Three series of experiments were conducted on Pagurus longicarpus and Clibanarius
      vittatus at Beaufort, North Carolina. The first series showed that the preferred
      species of shell by either species of crab is determined by the size of the crab
      and that certain species of shells are not available in preferred numbers for the
      hermit crab species. This affects C. vittatus more than P. longicarpus. The
      second series showed that shell fighting is not an important factor in
      determining which species occupies which kind of shell while the third series
      showed that a substrate preference for mud by P. longicarpus may limit it from
      obtaining a preferred species of shell that occurs naturally on sand.

PMID- 29323972
TI  - ELECTRICAL ACTIVITY ASSOCIATED WITH LUMINESCENCE AND OTHER COLONIAL BEHAVIOR IN
      THE PENNATULID RENILLA KOLLIKERI.

PMID- 29323973
TI  - EFFECTS OF HYDROGEN ION CONCENTRATION ON THE MORPHOLOGY OF HEMOCYTES OF THE
      MOLECRAB EMERITA ASIATICA.
AB  - Variations in the pH of the surrounding medium of hemocytes in vitro influence
      the morphology of granular hemocytes, the most predominant cell type in the
      hemocyte population of Emerita asiatica. Qualitative studies reveal that in the
      acidic range these cells become spindle-shaped and pseudopodial. Between pH 7.0
      and 9.0 of the Tris-HCl buffer system, the hemocytes show a sequential change.
      The morphological features of the stages are facsimiles of the major hemocyte
      types occurring in the hemolymph of Emerita asiatica. The granular hemocytes
      become plasmatocyte- and cystocyte-like cells. Differential counts of hemocytes
      and pH-induced variations of granular hemocytes reveal that the rate of change
      decreases with decreasing pH of the surrounding medium. The aggregation of
      hemocytes increases with increase in pH. The pH-dependent variations of hemocytes
      indicate that for a truly objective definition of hemocyte morphology and for a
      strict classification into distinctly separate cell types, experimental analyses
      of hemocyte morphology are required.

PMID- 29323974
TI  - BEHAVIOR AND ELECTRICAL ACTIVITY IN THE HYDROZOAN PROBOSCIDACTYLA FLAVICIRRATA
      (BRANDT). II. THE MEDUSA.
AB  - 1. Feeding in the medusa of Proboscidactyla flavicirrata is accompanied by local,
      small amplitude impulses recorded from the bases of perradial tentacles. 2.
      Medusae, both attached and free, swim spontaneously with electrodes in place thus
      giving data on the temporal patterns of contractions of the swimming muscle. 3.
      Swimming pulses (SP's) can be recorded from the circular muscle of the
      subumbrella. Each SP is preceded by a pre-swim pulse (PSP) which is a neuronal
      pulse conducted in the marginal nerve(s). 4. Marginal pulses (MP's) are neuronal
      pulses conducted in the marginal nerve(s) which can trigger synchronous tentacle
      contraction. 5. MP's originate from pacemaker sites located in tentacle bulbs.
      When new tentacles first appear the firing of MP's from these new sites is not
      synchronized with established pacemakers: eventually they become linked to the
      original pacemaker system. 6. Synchrony between MP pacemakers is lost under Mg++
      anaesthesia. 7. Tentacle contraction pulses (TCP's) are the electrical
      accompaniment to local tentacle contraction. 8. Crumpling pulses (CrP's) are
      epithelial pulses causing the protective behavior known as crumpling. 9. CrP's
      show a decrease in conduction velocity and amplitude as a result of repetitive
      stimulation.

PMID- 29323975
TI  - REPRODUCTION AND LARVAL DEVELOPMENT OF PSEUDOPOLYDORA PAUCIBRANCHIATA (OKUDA) AND
      PSEUDOPOLYDORA KEMPI (SOUTHERN) (POLYCHAETA: SPIONIDAE).
AB  - 1. The larval development of Pseudopolydora paucibranchiata (Okuda) and P. kempi
      (Southern) is described. Both species occur in tidal flats of California bays and
      estuaries. 2. Adult females of P. paucibranchiata deposit eggs in capsules which
      are attached to the inner lining of their tubes. All eggs are fertilized. Larvae
      develop in the capsules until they have 3 setigerous segments at which time they
      enter the plankton. After development of 13-17 setigers they begin to settle out
      of the plankton and assume a benthic life. 3. Eggs of P. kempi are also deposited
      in capsules, but in this case only a small percentage are fertilized. The
      unfertilized eggs fragment into separate yolk granules and are eaten by the
      developing embryos. After all yolk is devoured the larvae continue their
      development sustained by this stored food reserve. They remain in the capsule
      until they have about 15 setigers. They remain in the plankton only a short time
      before settling and taking up a benthic life.

PMID- 29323976
TI  - THE ONTOGENY AND SPECTRAL SENSITIVITY OF POLAROTAXIS IN LARVAE OF THE CRAB
      RHITHROPANOPEUS HARRISI (GOULD).
AB  - 1. To determine the ontogeny plus the intensity and spectral characteristics of
      polarotaxis in larvae of the crab, Rhithropanopeus harrisi, swimming paths in
      relation to the e-vector direction of linearly polarized light were monitored and
      recorded with a closed circuit video system. 2. All four zoeal stages were
      examined. Only stages II and III responded with significant directional swimming
      (stage II, perpendicular to the e-vector, stage III, parallel to the e-vector;
      Figs. 3 and 4). Stages I and IV appeared indifferent to the polarization plane
      (Figs. 2 and 5). Swimming under unpolarized light was consistently random (Table
      I). 3. Polarotaxis disappeared following dark adaptation of stage II larvae (Fig.
      6). 4. The lower intensity threshold at 499-nm light for polarotaxis was found to
      be between 10-4 and 10-3 W/m2, while the upper threshold is in the range 10-1 to
      2 x 10-1 W/m2 (Figs. 3 and 4). 5. Examination of selected wavelengths from 420
      620 nm yielded greatest responsiveness at 499 nm (Fig. 7). A rise evident at 420
      nm suggests a secondary maximum in the violet. 6. Stage II larvae showed
      significant positive phototaxis under depolarized light when a collar of
      alternating black and white quadrants surrounded the experimental vessel. With
      the e-vector of polarized light aligned parallel to the white sectors, phototaxis
      was reduced by polarotactic swimming into the black sectors (approximately
      perpendicular to the e-vector). 7. A comparison with phototaxis (Forward and
      Costlow, 1974) provides two items of evidence that polarotaxis and phototaxis are
      indeed separate responses. First, phototaxis is essentially unchanged during
      larval development, while polarotaxis appears only at stages II and III.
      Secondly, the responses have different optimum intensities.

PMID- 29323977
TI  - The personal tutor as a role model for students: humanising nursing care.
AB  - This article explores how nurse academics in one British university uphold and
      role model the humanising framework developed by Todres et al (2009) . It gives a
      brief overview of nurse education in the UK. Next it outlines the nature of the
      personal tutor role. It then offers an overview of the humanising framework, its
      background and embodiment in the undergraduate nursing curriculum. It explores
      how nurse academics role model humanisation and how this influences and impacts
      on students' ability to live and apply the humanising dimensions of nursing to
      enhance patients' lived experience of care. It concludes with examples of how
      this encourages positive meaningful relationships between students and tutors.

PMID- 29323978
TI  - Nurse-led epistaxis management within the emergency department.
AB  - BACKGROUND: the incidence of epistaxis has increased secondary to increased life
      expectancy and morbidities. This study sought to assess the knowledge, practice
      and opinion relating to adequacy of training of advanced nurse practitioners
      (ANPs) and staff nurses (SNs) in the emergency department. METHODS: a national
      survey was distributed over an 8-week period; this included a 3-point scoring
      system based on the National Institute for Health and Care Excellence Clinical
      Knowledge Summaries guidance on epistaxis management to assess overall
      performance. RESULTS: analysis included 109 ANPs and 101 SNs; 12% of ANPs
      achieved the maximum score, 40% scored 2, 25% scored 1, and 23% scored 0, while
      14% of SNs achieved the maximum score, 24% scored 2, 29% scored 1, and 32% scored
      0. Overall 88% of respondents advocated further training. CONCLUSION: significant
      deficits in knowledge regarding epistaxis management were highlighted. Further
      training could help to empower patients in basic first aid measures, subsequently
      reducing admissions rates.

PMID- 29323979
TI  - Outcomes of very high C-reactive protein levels in paediatric practice.
AB  - Siba Prosad Paul, Alifa De Aguiar, Joanna Barnden, Anna Cannon and Megan Eaton
      discuss the implications of high levels of the inflammatory marker, drawing on
      local audit.

PMID- 29323980
TI  - A commitment to making things better.
AB  - We hope that all nurses are committed to what they do, but what does that really
      mean? Clare Price-Dowd, Senior Programme Lead, NHS Leadership Academy, explores
      why commitment is fundamental for a nurse.

PMID- 29323981
TI  - A good mentor will never make you feel like a burden.
AB  - Ruth Stone, at the time of writing a final-year student at the University of East
      Anglia, reflects on the importance of an approachable, encouraging and sometimes
      challenging mentor for students on placement.

PMID- 29323982
TI  - Preparing for future incapacity: part 2.
AB  - In the second of two articles on the benefits of preparing for future incapacity
      Richard Griffith discusses the formal powers of the Mental Capacity Act 2005 that
      promote autonomy and give effect to a person's wishes and feelings.

PMID- 29323983
TI  - Safeguarding vulnerable adults.
AB  - Sam Foster, Chief Nurse, Oxford University Hospitals, focuses on the use of
      deprivation of liberty safeguards and the Mental Capacity Act and the importance
      of providing clarity for staff.

PMID- 29323984
TI  - Nurses and global health: 'at the table' or 'on the menu'?
AB  - Janet Scammell, Associate Professor (Nursing), Bournemouth University, looks at
      the role of the nursing workforce in shaping wider global health care, and the
      part nurse educators play in promoting international involvement.

PMID- 29323986
TI  - Improving flu campaigns: protecting healthcare workers and patients.

PMID- 29323985
TI  - Promoting improvements in mental health for children and young people.
AB  - Emeritus Professor Alan Glasper, University of Southampton, discusses a report
      from the Care Quality Commission into the current state of services for children
      and young people with mental health problems.

PMID- 29323987
TI  - Care bundles in the management of a COPD exacerbation.
AB  - Chronic obstructive pulmonary disease (COPD), the umbrella term used to describe
      chronic lung diseases that cause limitations in lung airflow, is predicted to be
      the third leading cause of death by 2030. COPD is said to affect 3 million people
      in the UK, resulting in approximately 30 000 deaths each year. Related healthcare
      costs continue to escalate, not least because of increasing readmission rates
      associated with COPD emergencies. The use of care bundles to streamline care is
      becoming more popular in an attempt to tackle this issue. An integrative
      literature review was carried out to examine the effectiveness of the use of care
      bundles. The findings highlighted inconsistencies in the components of bundles,
      leading to inherent difficulties in assessing which specific component of the
      bundles led to positive outcomes. The results of this attempt to establish the
      effectiveness of care bundles in reducing readmission rates and quality of care
      were inconclusive. The authors recommend further research to investigate the
      individual components in the bundles and to introduce internationally agreed care
      bundles for the management of COPD.

PMID- 29323988
TI  - The role of the Health Service Safety Investigations Body.
AB  - John Tingle, Associate Professor (Teaching and Scholarship), Nottingham Trent
      University, discusses the draft Health Service Safety Investigations Bill, which
      will create a new body with far-reaching legal powers.

PMID- 29323989
TI  - Rapid response: a multiprofessional approach to hospital at home.
AB  - The provision of 'hospital at home' is not new to the 21st century but pressure
      from the reduction in the number of hospital beds, population growth, an ageing
      population and subsequent extended time living with long-term conditions means
      such services are increasingly necessary. However, research by the authors found
      services that already exist do not operate 24 hours a day or provide a single
      multiprofessional approach. Gloucestershire's rapid response (RR) service
      provides specialist, coordinated, comprehensive and supportive assessment and
      treatment 24 hours a day in the patient's own home. Data were collected over a 5
      month period detailing the number of patients admitted to the service and its
      impact on hospital admission avoidance and patient outcome. The cost savings and
      reduction in length of hospital stay is considerable (to almost a quarter of the
      cost and number of bed days of an acute hospital admission). The position of the
      hospital as the main provider of urgent/acute care is shifting. The RR service
      demonstrates its position as a provider of an innovative service that breaks down
      the boundaries between acute, primary and social care.

PMID- 29323990
TI  - Ventilator-associated pneumonia and suction: a review of the literature.
AB  - AIM: to identify the most effective suctioning technique for the prevention of
      ventilator-associated pneumonia. BACKGROUND: ventilator-associated pneumonia is
      an important hospital-acquired infection associated with increased mortality and
      morbidity. METHOD: a rapid review included an electronic database search of
      articles published between January 2009 and March 2016. The quality of the seven
      included studies was appraised and data were subjected to tabular and narrative
      syntheses. RESULTS: closed suction systems have no clear advantage over open
      suction, but may better prevent late-onset ventilator-associated pneumonia.
      Subglottic secretion drainage reduces ventilator-associated pneumonia incidence.
      CONCLUSION: open versus closed suction combined with subglottic secretion
      drainage requires ongoing research. Alongside this, policy guidance, education,
      behavioural and managerial strategies must be implemented.

PMID- 29323991
TI  - Accuracy of non-invasive blood pressure measurements in obese patients.
AB  - This article describes an evidence-based literature review, comparing upper arm
      and forearm blood pressure measurements using non-invasive devices on obese
      patients. The focus on blood pressure monitoring was in response to regularly
      witnessing inappropriately applied blood pressure cuffs on obese patient's upper
      arms in practice. An inaccurately obtained blood pressure measurement can result
      in the misdiagnosis and treatment of hypertension. As the prevalence of obesity
      grows worldwide, healthcare settings need to ensure they have the necessary
      equipment and trained staff to accurately measure obese patients' blood pressure.
      The aim of this review was to identify whether a forearm measurement provided a
      suitable alternative to upper arm measurements. The article discusses the
      development and execution of a search strategy, as well as the critical appraisal
      of a selected article. The results of the review demonstrated that forearm blood
      pressure measurements in obese patients do not replace upper arm blood pressure
      measurements taken with an appropriate cuff. It is recommended that further
      research is undertaken in order to identify suitable alternatives for obtaining
      an accurate non-invasive blood pressure measurement in obese patients.

PMID- 29323993
TI  - Why you should be aware of CPE infection and transmission.

PMID- 29323992
TI  - Reducing catheter-associated urinary tract infections: standardising practice.
AB  - Inspired by innovations in catheter practice from the USA, in 2014 Nottingham
      University Hospitals NHS Trust introduced catheterisation standardisation across
      the Trust's two acute sites. Standardisation was achieved by the introduction of
      an all-in one catheterisation tray (Bard(r) Tray), which included all the
      necessary equipment required for catheterisation, coupled with a training
      programme. The introduction of the tray was followed by a clinically significant
      80% reduction in the CAUTI rate from 2014 to 2016. This reduction in CAUTI rate
      provided the Trust with a considerable reduction on annual expenditure (nearly
      L160 000 less in 2016 compared with 2014). The introduction of the tray has
      additionally improved practice with nursing staff now less likely to forget the
      necessary equipment before commencing catheterisation as all the components are
      provided in one place.

PMID- 29323994
TI  - You never stop learning.

PMID- 29323995
TI  - Short but was it sweet?

PMID- 29323996
TI  - ANTENNULAR CHEMOSENSITIVITY IN THE SPINY LOBSTER, PANULIRUS ARGUS: COMPARATIVE
      TESTS OF HIGH AND LOW MOLECULAR WEIGHT STIMULANTS.
AB  - Antennular chemoreceptors in the spiny lobster, P. argus, were surveyed
      electrophysiologically for responsiveness to natural stimuli of different
      molecular weights to gain further insight into the stimulatory role of
      macromolecules. Extracts and body fluids from eight potential food organisms were
      prepared and tested both before and after fractionation by ultrafiltration. Data
      presented verify chemosensitivity of lateral antennular filaments and show that
      for all extract types. the components of low molecular weight (< ca. 10,000) were
      significantly more stimulatory than the components of higher molecular weight;
      and stimulus values of low molecular weight fractions did not differ
      significantly from those of the unfractionated extracts.

PMID- 29323997
TI  - OXYGEN UPTAKE OF THE SOLITARY TUNICATE STYELA PLICATA.
AB  - 1. The oxygen consumption of the solitary tunicate Styela plicata was measured in
      order to estimate routine metabolic maintenance costs of the animal throughout
      the year. 2. The acclimatized oxygen consumption of Styela is proportional to the
      0.7 power of body weight; this value is independent of the acclimatization
      temperature. 3. Q10 declines with increasing temperature, averaging 3 between 10
      degrees  and 20 degrees  C, and 1.7 between 20 degrees  and 30 degrees  C. 4.
      Disproportionately large metabolic costs of routine activity cannot be invoked to
      explain the apparent lack of reproduction by Styela plicata during the warmest
      summer months. 5. The northern limit of Styela plicata is in the vicinity of Cape
      Hatteras, North Carolina. Winter mortality of adults is likely to limit the
      northern extension of Styela beyond Hatteras, and dislodgement from substrate
      during cold (growth inhibited) periods is suggested as one cause of winter
      mortality. 6. At temperatures greater than 10 degrees  C, oxygen uptake of Styela
      is independent of oxygen tension at normoxic conditions. An analysis of the
      critical oxygen tension as a function of temperature and body size suggests that
      ciliary activity may decrease the oxygen diffusion distance in the branchial sac
      at increased temperatures, and that the surface area per unit volume oxygen
      consumed may increase with increasing body size because of the demands of filter
      feeding on the branchial sac.

PMID- 29323998
TI  - SEASONAL VARIATIONS OF SODIUM AND POTASSIUM CONCENTRATIONS IN DIFFERENT PARTS OF
      THE FROG MYOCARDIUM.
AB  - Sodium and potassium concentrations in different parts of the frog heart (sinus
      venosus, atrium and ventricle) were investigated at various seasons of the year.
      The sodium concentration showed a marked periodicity in all three parts of the
      heart: minimum in winter, maximum in summer. Potassium concentration showed no
      seasonal variations, except for reduction in potassium concentration of the
      ventricle in the second half of the year. The experimental results for sodium can
      be fitted by a sine curve, the differences between minimum (in winter) and
      maximum (in summer) representing 46.4% (for sinus venosus), 30.4% (atrium) and
      34.0% (ventricle) of the spring-autumn values. Variation in the electrolyte
      concentration could be explained by changes in salt. and water metabolism induced
      by fluctuations in the temperature on one hand, and by the removal of the animals
      from their natural environment on the other.

PMID- 29323999
TI  - EFFECTS OF TEMPERATURE ON THE NUTRITIONAL REQUIREMENTS OF ARTEMIA SALINA (L.).
AB  - 1. The growth rate of Artemia in a uniform basic medium is faster at 30 degrees 
      C than at 25 degrees  C. 2. Temperature and salinity have opposite effects on the
      quantitative requirement for AMP. 3. At 30 degrees  C maximal growth is achieved
      with more AMP, more albumin, and less starch than at 25 degrees  C. 4. The
      effects of temperature are mediated by the ratio between energetic nutrients and
      AMP.

PMID- 29324000
TI  - COMPARATIVE STUDIES ON THE FUNCTION OF GILLS IN SUSPENSION FEEDING BIVALVES, WITH
      SPECIAL REFERENCE TO EFFECTS OF SEROTONIN.
AB  - 1. Observations were made on muscular and ciliary activity and particle transport
      and retention in intact gills and gill fragments of the suspension-feeding,
      epifaunal bivalves Anomia achaeus Gray, Juxtamusium maldivense (E. A. Smith),
      Pteria macroptera (Lamarck), Pycnodonte hyotis (L.), P. numisma (Lamarck),
      Crassostrea cuccullata (von Born), Crassostrea lugubris (Sowerby), Tridacna
      maxima (Roding), and T. squamosa Lamarck. 2. Gill contractions were especially
      violent in Pteria and both species of Pycnodonte. 5-HT in concentrations of 10-4
      10-5 M caused relaxation of contracted gills, and reduced or abolished the
      response to mechanical stimulation, except in Tridacna. 3. In Juxtamusium, the
      concertina-like movements of the gill plicae could be correlated with the
      functional state of the water-transporting lateral cilia. When all lateral cilia
      were active, and the plicae inflated, movements of the plicae were discontinued.
      At periods of arrest of the lateral cilia the plicae collapsed and resumed
      concertina-like movements. 5-HT had no clear effect on the concertina-like
      movements of the gill plicae, except in Juxtamusium in which addition of 5-HT to
      the ambient medium stimulated the movements. 4. Exposed gills or gill fragments
      of all the species examined continued to transport water, but only inefficiently
      retained particles, 10-20 um Tetraselmis cells, added to the water. 5-HT enhanced
      the rate of water transport in most species by stimulating the activity of the
      lateral cilia, but reduced the ability of the gill to retain Tetraselmis cells.
      The cilio-excitatory nerve transmitter 5-HT of bivalve gill filaments thus did
      not restore normal feeding activity of the gill. 5. Latero-frontal cirri could
      not be distinguished on the gill filaments of Anomia, Juxtamusium, and Pteria. In
      Crassostrea lugubris they were small (ca. 13 um, in length) and inconspicuous.
      They were about 15 um long in the two species of Tridacna, and about 17 um long
      in Crassostrea cuccullata and in the two species of Pycnodonte, spanning about
      half of the interfilamentar space in relaxed plicae. The latero-frontal cirri
      varied greatly in activity and in orientation of inactive cirri. Also the effects
      of 5-HT were variable, but the drug tended to arrest the cirri in an erect
      position. 6. 5-HT reduced the creeping rate of gill fragments of Pycnodonte
      numisma. 7. The gill fragments secreted mucus at low rates even in dense
      suspensions of Tetraselmis cells. The majority of Tetraselmis cells that were
      retained and transported by the gill fragments remained free of mucus, to be
      redispersed in the medium when they arrived at cut ends of the particle
      transporting ciliary tracts along the gill bases or the ventral margins of the
      demibranchs. 8. It is concluded that the feeding state of the bivalve gill, which
      is characterized by high rates of water transport through highly retentive gills,
      is restricted to undisturbed, intact animals. The mechanisms of feeding,
      therefore, cannot be finally understood from studies on exposed gills or gill
      fragments. The physiological significance of the nonretentive gill of disturbed
      animals and gill preparations is not clear.

PMID- 29324002
TI  - ABSTRACTS OF PAPERS PRESENTED AT THE MARINE BIOLOGICAL LABORATORY.

PMID- 29324001
TI  - FLOW AND FEEDING IN FAN-SHAPED COLONIES OF THE GORGONIAN CORAL, LEPTOGORGIA.
AB  - Field studies demonstrate that the gorgonian coral Leptogorgia virgulata assumes
      a fan-shaped morphology oriented at right angles to prevailing tidal currents.
      Laboratory studies using a recirculating water tunnel and Artemia salina nauplii
      as food show that fan-shaped colonies oriented perpendicular to water currents
      capture more Artemia per unit time than the same colonies oriented parallel to
      water currents. Several feeding strategies which may operate at various current
      speeds are suggested. Possible mechanisms controlling feeding response and the
      selective advantage of colony morphology and orientation as related to feeding
      and resistance to hydrodynamic forces are discussed.

PMID- 29324003
TI  - CYTOTOXIC EFFECTS OF THE HERBICIDE 3-AMINO-1,2,4-TRIAZOLE ON DAPHNIA PULEX
      (CRUSTACEA:CLADOCERA).
AB  - Zero to 24 hour old specimens of Daphnia were exposed to 10 ppm 3-amino-1,2,4
      triazole at 24 degrees  C until immobilized. The most consistent alteration in
      cell structure was expressed by the mitochondria especially those of muscle
      fibers. Not all muscle cells within a single animal nor all mitochondria within a
      single cell were affected equally. The most common alteration observed was
      folding of the outer membrane. This was accompanied by organelle swelling and a
      reduction in electron density of the ground matrix and number of cristae. In
      addition other cytotoxic effects were observed. These included general tissue
      swelling, disarrangement of myofilaments and dissociation of membranes. Mobile 0
      24 hr old daphnids which were exposed to the herbicide for up to 15 hr showed no
      cell or organelle damage regardless of length of exposure. Data from acute static
      experiments suggest that the time of immobility is closely related to molt for 0
      24 hr juveniles.

PMID- 29324004
TI  - SCANNING ELECTRON MICROSCOPY OF THE REGENERATED SHELL OF THE MARINE
      ARCHAEOGASTROPOD, TEGULA.
AB  - A window was cut in the first body whorl of the marine snail, Tegula, to induce
      shell regeneration. At various intervals after the shell window was cut, the
      window with the regenerated material and the shell surrounding it were prepared
      for scanning electron microscopy. Initial crystal deposition occurred in
      association with an organic matrix and appeared as small, spindle-shaped crystals
      formed by the aggregation of needle-like subunits. The spindles were frequently
      aggregated into stellate clusters that coalesced to form a sheet of mineralized
      tissue. After about two months of regeneration, dumbbell-shaped crystal
      aggregates and spherulites were apparent on the surface of the regenerated shell.
      The regenerated shell assumed a normal structure after at least four months of
      regeneration. Crystal deposition also occurred on the normal shell bordering the
      shell window. The crystals assumed several forms, and their orientation appeared
      to be determined by the microtopography of the underlying shell.

PMID- 29324005
TI  - MORPHOLOGY AND GENETICS OF REJECTION REACTIONS BETWEEN OOZOOIDS FROM THE TUNICATE
      BOTRYLLUS SCHLOSSERI.
AB  - Botryllus rejection reactions were followed in pairs of oozooids placed together
      immediately after initiation of metamorphosis. Within twelve hours, both
      compatible and incompatible oozooid pairs underwent tunic fusion and initiation
      of ampullar tip-to-side contact. Vascular fusion followed within two days between
      compatible pairs, while the fusion sequence was interrupted in the incompatible
      pairs by a rapid cytotoxic rejection response. Events occurring within and
      outside the ampullae in rejections were effector responses whose consequences
      were separation of the ampullae and isolation of the involved tissues from the
      bodies of the oozooids. Genetics experiments suggested that the four distinct
      types of rejection reflect a hierarchy of histoincompatibility in this system.

PMID- 29324006
TI  - COMPETITIVE DISPLACEMENT OF NATIVE MUD SNAILS BY INTRODUCED PERIWINKLES IN THE
      NEW ENGLAND INTERTIDAL ZONE.
AB  - During the nineteenth century the mud snail Ilyanassa obsoleta was abundant on
      sand and mud flats, wood works, sea walls, salt marshes, eel grass beds, and
      cobble beaches in New England. With the exception of sand and mud flats, these
      habitats are now largely occupied by the introduced periwinkle, Littorina
      littorea. To determine whether Littorina competitively displaces Ilyanassa, an
      experimental study was conducted at a site in Barnstable Harbor, Massachusetts
      where the observed distributions overlapped by 3% by Morisita's index. Mark
      recapture studies suggested that the distribution of Littorina was limited by an
      abiotic factor, currents, through which this species realized its fundamental
      niche. In contrast, density manipulations demonstrated that Ilyanassa emigrated
      from areas where Littorina exceeded densities of 2 to 5 per 0.25 m2. Littorina
      limited the upper and lower distribution of Ilyanassa and affected its
      microhabitat distribution in the mid intertidal zone. Habitat displacement was
      70% for Ilyanassa, calculated as the difference between Ilyanassa's observed
      distribution and its distribution during littorinid removal experiments. The two
      species display reciprocal niche overlap with each possessing an exclusive region
      from which the other is physically restricted. The results suggest that the
      historical change in the distribution of Ilyanassa was due to competitive
      exclusion by introduced Littorina.

PMID- 29324007
TI  - FEEDING STRUCTURES, BEHAVIOR, AND MICROHABITAT OF ECHINOCYAMUS PUSILLUS
      (ECHINOIDEA: CLYPEASTEROIDA).
AB  - In the Firth of Lorne, Scotland, Echinocyamus pusillus was found most abundantly
      in highly variable, poorly sorted substrates at depths of 10-20 m. It was common
      in areas exposed to extensive wave and tidal current activity, but absent in fine
      sediments in sheltered areas. In size, feeding mechanism, and behavior, the
      species is highly adapted for nestling in the interstices between relatively
      large pebbles. The feeding mechanism is atypical for clypeasteroids: substrate
      particles with attached organisms are selected and transported by the suckered
      podia. At the mouth, particles are held in place and slowly rotated by the free
      margin of the peristomial membrane, while the teeth strip away diatoms and
      organic debris. The peristomial membrane and ciliation of spines and podia are
      shown in scanning electron micrographs of critical point dried material. The
      histology of these structures is described with special reference to mucus
      secretion. High resolution SEM micrographs show mucus secreting pores among the
      epithelial microvilli of suckered and buccal podia but not in the epithelium of
      miliary spines. The suggestion that E. pusillus might represent a sand dollar
      ancestor is discussed. The evidence presented supports the view that it is
      specialized rather than primitive.

PMID- 29324008
TI  - THE BIOLOGY OF FISSURELLA MAXIMA SOWERBY (MOLLUSCA: ARCHAEOGASTROPODA) IN
      NORTHERN CHILE. 2. NOTES ON ITS REPRODUCTION.
AB  - For 14 months, monthly samples were collected to study reproduction in Fissurella
      maxima at Huayquique. Results indicate that F. maxima is a dioecious species; no
      sign of hermaphroditism has been observed. The sex ratio is 1:1 in the different
      size classes analyzed. Ovaries are green and testis are median brown to yellowish
      white. Eggs in the ovary measure from 120-280 u without envelopes. The gonads are
      parasitized by adult digenea trematods of the genus Proctoeces. Some effects of
      parasitism are discussed. Variations in mean monthly gonadosomatic index suggest
      that there is a main spawning period in late November-December (late spring-early
      summer) and a secondary period in July-August (winter). Fluctuations in mean
      gonad index show a close correlation with sea water temperature variations. The
      youngest mature specimens detected were about 5 cm in shell length (over two
      years old), but the majority of mature animals were over 6.5 cm.

PMID- 29324009
TI  - THE ROLES OF HEMOCYTES IN TANNING DURING THE MOLTING CYCLE: A HISTOCHEMICAL STUDY
      OF THE FIDDLER CRAB, UCA PUGILATOR.
AB  - Histochemical data support the previous biochemical finding that the blood is a
      major site for the production of proteinaceous and diphenolic substances for
      tanning of the cuticle in the fiddler crab, Uca pugilator. Five types of
      hemocytes are described. Specifically in tanning, the hyaline cells (cystocytes)
      appear responsible for the production of diphenolic tanning agents whereas the
      granulocytes synthesize the proteins involved. Other types of hemocyte may be
      transitional forms involved in clotting (intermediate cells). Various
      histochemical reactions for each type of hemocyte and the cuticle are recorded
      throughout the molting cycle, and appear cyclic. The data suggest there is
      hormonal control of the cyclic events during the tanning process.

PMID- 29324010
TI  - INDUCED DEVELOPMENT OF SWEEPER TENTACLES ON THE REEF CORAL AGARICIA AGARICITES: A
      RESPONSE TO DIRECT COMPETITION.
AB  - The scleractinian coral Agaricia agaricites often has elongate sweeper tentacles
      on colony margins close to other sessile animals. Sweeper tentacles can damage
      tissues of opponents and are probably used in direct competition for substrate
      space. Furthermore, contact with tissues or mesenterial filaments of other
      corals, or with tissues of the gorgonian Erythropodium caribaeorum or the
      zooanthid Palythoa caribbea can stimulate the development of sweeper tentacles by
      A. agaricites. Depending on both the particular competitor species involved and
      the distance separating it from A. agaricites, events leading to the development
      of sweeper tentacles may or may not include tissue loss by A. agaricites. On
      average the development of sweeper tentacles takes thirty days, and is localized
      exclusively on tissues close to the region in contact with competitors. Sweeper
      tentacles do not develop in response to artificial stimuli simulating tactile
      contact or damage such as occur in natural interactions with other corals. Thus,
      recognition of competitor tissues appears to be a necessary stimulus for sweeper
      formation.

PMID- 29324011
TI  - REGENERATION OF INJURIES AMONG JAMAICAN GORGONIANS: THE ROLES OF COLONY
      PHYSIOLOGY AND ENVIRONMENT.
AB  - The consequences of injury to reef dwelling colonial animals are determined
      partly by rates of regeneration of lost tissues. These experiments examined two
      potential influences on regeneration rates of Jamaican gorgonians: 1) intrinsic
      physiological and energetic differences among co-occurring, conspecific colonies
      differing in size, reproductive phase, or injury location; and 2) differential
      responses among three plexaurid species to changing environmental variables
      across their depth range. In Plexaura homomalla, regeneration rate varied with
      the location of injury within colonies, but was unexpectedly independent of
      either colony size or reproductive phase. In addition, colonies of P. homomalla,
      Eunicea mammosa, and Plexaurella dichotoma differed in relative ability to
      regenerate equivalent injuries in different reef zones across their depth range.
      "There is one fact in the life-history of corals which the study of processes of
      repair clearly brings out, and it is this, that all the methods of regeneration
      are more for the life-saving of the colony than of the individual." Wood-Jones,
      1912.

PMID- 29324012
TI  - ANALYSIS OF HEMOLYMPH OXYGEN LEVELS AND ACID-BASE STATUS DURING EMERSION 'IN
      SITU' IN THE RED ROCK CRAB, CANCER PRODUCTUS.
AB  - Hemolymph samples were taken from small (< 100 g) individuals of Cancer productus
      following ca. 3 h air exposure (emersion) on the beach, 'in situ', at Friday
      Harbor, Washington. Compared with crabs of similar size in sea water in the
      laboratory, these crabs emersed 'in situ' had lower Pao2, and Pvo2, but no
      significant change in pH and a small, not significant, internal hypercapnia.
      Total CO2 (Cco2) content of the hemolymph was elevated by 70% (15.2 versus 9.0
      mM), possibly as compensation for input of acid into the hemolymph. These
      responses are qualitatively similar to those resulting from similar treatment in
      the laboratory, but differ in the reduced magnitude of the internal hypercapnia
      and acidosis of the hemolymph. It is suggested that the particular conditions of
      emersion 'in situ' permit some gas exchange with interstitial sea water.
      Interstitial sea water was found to be hypoxic (Po2 = 20-40 torr), which would
      limit oxygen supply yet permit CO2 excretion to continue, in agreement with the
      data.

PMID- 29324013
TI  - MARINE BIOLUMINESCENCE SPECTRA MEASURED WITH AN OPTICAL MULTICHANNEL DETECTION
      SYSTEM.
AB  - The emission spectra of 70 bioluminescent marine species were measured with a
      computer controlled optical multichannel analyzer (OMA). A 350 nm spectral window
      is simultaneously measured using a linear array of 700 silicon photodiodes,
      coupled by fiber optics to a microchannel plate image intensifier on which a
      polychromator generated spectrum is focused. Collection optics include a quartz
      fiber optic bundle which allows spectra to be measured from single photophores.
      Since corrections are not required for temporal variations in emissions, it was
      possible to acquire spectra of transient luminescent events that would be
      difficult or impossible to record with conventional techniques. Use of this
      system at sea on freshly trawled material and in the laboratory has permitted
      acquisition of a large collection of bioluminescence spectra of precision rarely
      obtained previously with such material. Among unusual spectral features revealed
      were organisms capable of emitting more than one color, including: Umbellula
      magniflora and Stachyptilum superbum (Pennatulacea), Parazoanthus lucificum
      (Zoantharia), and Cleidopus gloria-maris (Pisces). Evidence is presented that the
      narrow bandwidth of the emission spectrum for Argyropelecus affinis (Pisces) is
      due to filters in the photophores.

PMID- 29324014
TI  - EXPERIMENTAL STUDIES ON EMBRYOGENESIS IN HYDROZOANS (TRACHYLINA AND SIPHONOPHORA)
      WITH DIRECT DEVELOPMENT.
AB  - The normal embryology of the trachymedusa Aglantha digitale and the siphonophores
      Nanomia cara and Muggiaea atlantica is described. Marking experiments on these
      embryos indicate that the site of first cleavage initiation corresponds to the
      oral pole of the oral-aboral axis. In Muggiaea the plane of the first cleavage
      corresponds to the plane of bilateral symmetry. Experiments in which presumptive
      aboral and oral regions are isolated from these embryos at different stages of
      development indicate that there is an early determination of different regions
      along this axis. Only the oral region of the Muggiaea embryo has the ability to
      regulate. These eggs have a pronounced centrolecithal organization. As a
      consequence of cleavage, the outer ectoplasmic layer of the egg ends up in the
      cells that form the ectoderm, while the inner or endoplasmic region of the egg
      ends up in the cells that form the endoderm. Experimentally created fragments of
      fertilized eggs that contain only ectoplasm differentiate to form an unorganized
      ectodermal cell mass, indicating that endoplasm is necessary in order to
      differentiate endoderm. The process of embryogenesis in these animals and the
      developmental mechanisms they use are very different from those used by
      hydrozoans with indirect development. These embryos use a suite of developmental
      mechanisms which are very similar to those used by ctenophores. The significance
      of this similarity is discussed.

PMID- 29324015
TI  - CIRCULATION OF FLUIDS IN THE GASTROVASCULAR SYSTEM OF THE REEF CORAL ACROPORA
      CERVICORNIS.
AB  - Circulation of fluids in the gastrovascular system of A. cervicornis was
      determined by observing the movement of fluorescein dye injected via a lateral
      polyp and viewed in the dark under ultra-violet light. Scanning electron
      microscopy and petrographic thin sections were used to describe the general
      morphology of the gastrovascular system. This consists of two functional units:
      an axial unit composed of the coelenteron of the axial polyps and a peripheral
      unit composed of tubes oriented axially ramifying through the skeleton lying just
      beneath the outer ectoderm. These units are connected by radially oriented tubes
      including the coelenterons of the lateral polyps. The entire gastrovascular
      system is lined by flagellated endoderm cells. Flow in the axial unit is always
      proximal. Flow in the peripheral unit is both distal and proximal and the
      velocity is always less than the flow in the axial unit. Light does not appear to
      change the rate of flow. Rates of flow in the peripheral unit show a diel cycle,
      with increased flow rates occurring between 2100 and 0600.

PMID- 29324016
TI  - SPATIAL AND TEMPORAL PATTERNS OF MITOSIS IN THE CELLS OF THE AXIAL POLYP OF THE
      REEF CORAL ACROPORA CERVICORNIS.
AB  - The fluorescent stain DAPI was used to observe mitoses in the endoderm and the
      calicoblastic ectoderm of the axial polyp of the reef coral Acropora cervicornis.
      A diel periodicity in the mitotic index (defined as the percentage of cells in
      some stage of mitosis) of each tissue occurred with a maximum of about 2% at
      midnight and a minimum of 0.5% at midday. Dividing cells were located from the
      tip of the column (when the polyp was contracted into the calyx) to 10 mm
      proximal to this point suggesting that there is no narrow zone of proliferating
      cells. The magnitude of the mitotic indices of these tissues suggests that it may
      account for the observed daily growth rate of ca. 300 um in the axial polyp.

PMID- 29324017
TI  - SURVIVAL, GROWTH, AND BEHAVIOR OF THE LOLIGINID SQUIDS LOLIGO PLEI, LOLIGO
      PEALEI, AND LOLLIGUNCULA BREVIS (MOLLUSCA: CEPHALOPODA) IN CLOSED SEA WATER
      SYSTEMS.
AB  - Over 1200 squids were captured by night lighting, trawling, or seining in the
      northern Gulf of Mexico for laboratory maintenance. Two types of recirculating
      sea water systems were designed and evaluated: a 2 m circular tank (1500 liter
      capacity) and a 10 m long raceway (10,000 liters). Mean laboratory survival was:
      Loligo plei (12 to 252 mm mantle length, ML) 11 days, maximum 84 days; Loligo
      pealei (109 to 285 mm ML) 28 days, maximum 71 days; Lolliguncula brevis (27 to 99
      mm ML) 19 days, maximum 125 days. Smaller squids showed significantly poorer
      survival than larger ones. All squids fed well on a variety of live estuarine
      fishes and shrimps. Growth rates depended upon stage of maturity. The highest
      rates were Loligo plei 59 mm/month (23.8 g/mo), Loligo pealei 77 mm/mo (67.3
      g/mo), and Lolliguncula brevis 31 mm/mo (17.2 g/mo). General aspects of behavior
      and body patterning were species-specific and were useful indices of the squids'
      condition. Key factors for laboratory survival were (1) prevention of skin
      damage, (2) tank systems with sufficiently large horizontal dimensions, (3) high
      quality water, (4) ample food supply, (5) no crowding, (6) maintaining squids of
      similar size to reduce aggression and cannibalism, and (7) segregating sexes to
      reduce aggression associated with courtship, mating, and egg laying.

PMID- 29324018
TI  - THE LATITUDINAL COMPENSATION HYPOTHESIS: GROWTH DATA AND A MODEL OF LATITUDINAL
      GROWTH DIFFERENTIATION BASED UPON ENERGY BUDGETS. I. INTERSPECIFIC COMPARISON OF
      OPHRYOTROCHA (POLYCHAETA: DORVILLEIDAE).
AB  - A northern (North Carolina) sibling species of Ophryotrocha grew more rapidly
      than a southern sibling species (Florida); this presumed advantage, however,
      diminished to zero as temperature increased from 15 to 30 degrees C. Survival of
      the northern sibling species was low at 30 degrees C. The differential response
      probably had a genetic basis since both species had been reared for 2-3
      generations under the same conditions. The effect lasted in laboratory
      populations reared for a year in the laboratory at 25 degrees C (ca. 10
      generations). My results are consistent with a graphical model that suggests an
      evolutionary shift of metabolism-temperature curves and feeding efficiency curves
      for the two sibling species. These shifts predict a changing advantage of growth
      of one species relative to the other as temperature increases.

PMID- 29324019
TI  - THE LATITUDINAL COMPENSATION HYPOTHESIS: GROWTH DATA AND A MODEL OF LATITUDINAL
      GROWTH DIFFERENTIATION BASED UPON ENERGY BUDGETS. II. INTRASPECIFIC COMPARISONS
      BETWEEN SUBSPECIES OF OPHRYOTROCHA PUERILIS (POLYCHAETA: DORVILLEIDAE).
AB  - Individuals of two subspecies of Ophryotrocha puerilis (Polychaeta; Dorvilleidae)
      were collected from differing thermal regimes, and cultures were maintained for
      over a year. Despite common rearing, the two subspecies show substantial
      differences in somatic growth rate. At 15 degrees C, the warm-water subspecies
      grew more slowly, while at 20 degrees C growth for the two subspecies was not
      significantly different. At 24 degrees C, the warm-water subspecies grew more
      rapidly and suffered substantially less mortality than the northern subspecies.
      These results conform to a model predicting genetic differentiation of metabolic
      efficiency, leading to differences in growth efficiency among populations
      adapting to thermally differentiated habitats. The problems faced by the cold
      water subspecies at 24 degrees C conforms to expectations based upon natural
      habitat temperatures.

PMID- 29324020
TI  - ENERGY METABOLISM DURING AIR EXPOSURE AND RECOVERY IN THE HIGH INTERTIDAL BIVALVE
      MOLLUSC GEUKENSIA DEMISSA GRANOSISSIMA AND THE SUBTIDAL BIVALVE MOLLUSC MODIOLUS
      SQUAMOSUS.
AB  - Metabolic responses to air exposure and recovery were investigated in the
      adductor muscles of the high intertidal mussel Geukensia demissa granosissima and
      the subtidal mussel Modiolus squamosus. Exposure to air for 12 h had no
      significant effect on the levels of high energy phosphates (arginine phosphate,
      ATP) in the adductor muscles of G. demissa granosissima, indicating minimal
      metabolic stress in this species. In contrast, there was a considerable decline
      in arginine phosphate and ATP during air exposure in the phasic and tonic
      adductor muscles of M. squamosus. In addition, there was a substantial
      accumulation of alanine and succinate under these conditions. Furthermore, D
      lactate accumulated in the phasic muscle of M. squamosus during air exposure.
      During recovery, there were transient accumulations of alanopine/ strombine in
      both G. demissa granosissima and M. squamosus. The differences in metabolic
      responses between these two species reflect adaptations to specific micro
      habitats. It appears that metabolism in the posterior adductor muscle of G.
      demissa granosissima is largely aerobic during air exposure. The subtidal species
      M. squamosus displays a much greater reliance on anaerobic pathways of energy
      production under these conditions.

PMID- 29324021
TI  - STUDIES ON THE REPRODUCTIVE SYSTEMS OF SEA-STARS. II. THE MORPHOLOGY AND
      HISTOLOGY OF THE GONODUCT OF ASTERIAS VULGARIS.
AB  - In Asterias vulgaris there are 10 separate units of the reproductive system, each
      with its own distinct gonoduct. The gonoduct forms late in the life of the sea
      star as an outgrowth of the inner sac of the gonad. During its formation, each
      gonoduct grows from the gonad to the body wall where it burrows through a layer
      of connective tissue located below the parietal peritoneum. The gonoduct follows
      this subperitoneal connective tissue into a coelomic pocket (which ends
      externally in several dermal branchiae) and ultimately penetrates the dermis,
      where it divides into subsidiary ducts which open separately in the external
      epithelium of the interradius. The gonoduct consists of an outer elastic
      connective tissue layer continuous with both walls of the haemal sinus of the
      inner sac of the gonad and an inner epithelial layer continuous with the germinal
      epithelium of the gonad. Near the point where the gonoduct opens into the lumen
      of the gonad, the epithelial layer of the gonoduct forms cross-ridges which span
      the lumen of the duct and imbricate, partially blocking the lumen.

PMID- 29324022
TI  - SHELL GROWTH IN THE SCALLOP ARGOPECTEN IRRADIANS. I. ISOTOPE INCORPORATION WITH
      REFERENCE TO DIURNAL GROWTH.
AB  - 1. Incorporation of calcium and carbonate into shell has been studied in the
      scallop Argopecten irradians using 45Ca and 14C-bicarbonate. 2. The incorporation
      of 45Ca and 14C-carbonate into shell was linear with time after a lag period of 1
      to 2 hours. The shell-forming mantle tissue attained a steady state with respect
      to 45Ca in the sea water medium within 2 hours. 3. The molar ratio of 45Ca to 14C
      carbonate deposited in shell was not significantly different from unity during 5
      hours. 4. The rate of incorporation of 14C-carbonate into shell was highest at
      the ventral edge and extremely low in the central and hinge areas. 5. The rate of
      incorporation at the ventral shell edge did not change with increase in shell
      size. 6. The rate of incorporation of carbonate was low at night when growth
      ridges form and increased 3-fold at midday when growth ridges are not being
      formed. 7. The protein content of the shell ridges was 32.9 +/- 3.9% and the
      protein content of the shell including ridges was 16.0 +/- 2.1%.

PMID- 29324023
TI  - AGONISM IN ASTEROIDS.
AB  - 1. Intraspecific agonistic behavior, called bouts, which involves ray
      interactions between individual sea stars, is reported in species from all three
      living orders of asteroids and described for Patiria miniata and Pycnopodia
      helianthoides. This behavior indicates a certain sensitivity to conspecific
      contact on the aboral surface, in which each individual attempts to place a ray
      or rays on top of its opponent, an act which may initiate opponent withdrawal.
      Agonistic intraspecific bouts affect the distribution and feeding of both species
      although bouts may take place where food is not present. 2. Patiria bouts may
      last over two hours and sometimes terminate by individuals overlapping and
      sharing food. Evidence suggests that Patiria bouts are: (a) quite common; (b) not
      related to sexual behavior; (c) territorial; and (d) influenced as to outcome by
      relative body orientation; however, when territorial behavior is involved,
      relative body orientation does not affect bout outcomes. Pycnopodia bouts are of
      shorter duration (up to 10 minutes), terminating with the withdrawal of one or
      both animals, and sometimes resulting in an extensive pursuit. 3. Two forms of
      intraspecific Patiria bouts are noted: continuous-contact and intermittent
      contact. Intermittent-contact bouts appear less intensive, permitting individuals
      to feed and to engage in bouts with more than one opponent at a time. It is
      speculated that intermittent-contact bouts are a type of ritualized activity of a
      fairly complex nature. 4. Interspecific bouts between specimens of Pycnopodia and
      two species of Pisaster (P. giganteus and P. brevispinus) have been observed only
      when the Pisaster sp. is in possession of food. Pycnopodia individuals approach
      and place rays on the aboral surface of the feeding sea star while attempting to
      obtain the food with other rays. The specimen of Pisaster sp. actively
      counterattacks using its pedicellariae.

PMID- 29324024
TI  - NON-EQUIVALENCE FOR BEAN SEEDS OF CLOCKWISE AND COUNTERCLOCKWISE MAGNETIC MOTION:
      A NOVEL TERRESTRIAL ADAPTATION?
AB  - 1. Three experiments on water-uptake in pinto beans, Phaseolus vulgaris, during
      their first four hours in water have all indicated that clockwise and
      counterclockwise rotating magnetic fields have statistically significantly
      different effects upon the rate of the process. 2. The results suggest that this
      difference is independent of time and place. Critically performed experiments at
      Evanston, Illinois and Woods Hole, Massachusetts, over more than a two-year span,
      all gave essentially the same results. 3. A clockwise rotating magnetic field
      abolished, for the beans, a correlation with concurrent control beans without
      magnet, while a counterclockwise rotating magnet failed to do so. 4. In a
      concurrent series involving rotating beans (1 rpm, clockwise and
      counterclockwise) and beans in fields of a weak rotating magnet (1 rpm, clockwise
      and counterclockwise), the effects of counterclockwise magnet and
      counterclockwise table rotations were of opposite character and highly
      significantly different from one another. Effects of clockwise magnet and
      clockwise table rotations differed significantly, in turn, from their opposite
      directions of rotations. 5. The results uniformly support the hypothesis that the
      different effects reported between clockwise and counterclockwise rotation of
      organisms result from their systematic, directional motions relative to the
      geomagnetic field. 6. It is postulated that this non-equivalence for organisms of
      clockwise and counterclockwise rotations of such extremely weak magnetic fields
      reflects a novel and fundamental adaptation of organisms to their rotating and
      sun-orbiting environments.

PMID- 29324025
TI  - DEVELOPMENT OF BIOLUMINESCENCE AND OTHER EFFECTOR RESPONSES IN THE PENNATULID
      COELENTERATE RENILLA KOLLIKERI.
AB  - 1. The development of the pennatulid coelenterate Renilla kollikeri was followed
      from fertilized egg to primary polyp stage, including observations on the
      development of effector responses such as ciliary swimming, muscular reactions
      and bioluminescence. 2. Ciliary swimming is first apparent in the early planula,
      32 hr after the spawn. Ciliary activity persists until settlement, at
      approximately 130 hr. 3. Muscular reactions are first evident as local
      contractions in the swimmer stage (about 60 hr). Conducted contractions can be
      elicited at 80 hr, suggesting that a functional conduction system is present in
      the planula larva. At settlement, separate peduncular and anthocodial muscular
      responses and peristaltic contractions are evident. 4. The future photocytes
      first fluoresce at about 80 hr, and thereafter fluorescence intensity increases
      until the time of settlement. The first sign of bioluminescence follows
      settlement, and is delayed if settlement is prevented. Bioluminescent responses
      do not exhibit normal facilitation until the primary polyp stage, and responses
      of the preceding stages may reflect maturation of the colonial and polyp
      conduction systems as well as of connections between the two systems. 5.
      Settlement and metamorphosis are delayed when planulae are reared in containers
      without sand.

PMID- 29324026
TI  - ON FEEDING MECHANISMS AND CLEARANCE RATES OF MOLLUSCAN VELIGERS.
AB  - 1. Beat of preoral cilia and particle paths were filmed for veligers of
      Crassostrea gigas, Tritonia diomedea, Nassarius obsoletus and an unidentified
      prosobranch. Particle captures were filmed for the three identified species. 2.
      Clearance rates per unit length of velar edge are estimated from the equation (L2
      R2)WPF/2C, where L is cilium length, R a correction for recovery stroke, W
      angular velocity, C/P the ratio of velocities of cilium and particle, and F the
      fraction of particles captured. The clearance rates are in rough agreement with
      Bayne's values for veligers of Mytilus edulis. 3. In the three identified
      species, longer preoral cilia clear particles at a higher rate but with less
      efficiency. Since veligers from larger eggs generally have both longer preoral
      cilia and a longer velar edge, a larger egg generally produces a veliger with a
      higher maximum clearance rate when the veliger begins to feed. 4. Angular
      velocities increase with cilium length in the three identified species of
      veligers but the larger unidentified species did not continue this trend. 5.
      Preoral cilia in their effective strokes move 1 to 3 times faster than particles
      travelling in about the same arc with a mean of about 1.5 times the speed of the
      particles. In mid effective stroke, the ratio of velocities of cilia and
      particles is not significantly different for captured and non-captured particles,
      nor does the ratio vary significantly with angular velocity of cilium. The ratio
      does vary significantly among species. 6. Particles passing closer to the base of
      the preoral cilia are more likely to be captured. 7. We hypothesize that
      suspended particles are concentrated when they are overtaken by preoral cilia in
      their effective stroke, weakly adhere to the preoral cilia, and are pushed faster
      than the water. Capture is completed when particles are drawn into the food
      groove, probably by the action of the recovery stroke of preoral cilia, the
      current from postoral cilia, or both.

PMID- 29324027
TI  - IRREVERSIBLE NONGENETIC TEMPERATURE ADAPTATION OF OXYGEN UPTAKE IN CLONES OF THE
      SEA ANEMONE HALIPLANELLA LUCIAE (VERRILL).
AB  - 1. Isogenic clones of H. luciae were raised at each of two developmental
      temperatures, 18 degrees  and 28 degrees  C. Despite prolonged acclimation to
      common thermal conditions, oxygen uptake rates differ according to the
      temperature of reproduction, regeneration and development. 2. The effects of
      developmental temperature, however, are masked by body size differences. Only
      when this variable is eliminated can the underlying effect of developmental
      temperature be detected. 3. The irreversible change is not due to an increase in
      the gas exchange surface area at the primary site of O2 uptake, the tentacles. 4.
      No qualitative changes in banding patterns for five enzymes (HK, PGI, IDH, MDH, G
      6-PDH) were found.

PMID- 29324028
TI  - A FIELD STUDY OF GROWTH AND REPRODUCTION IN APLYSIA CALIFORNICA.
AB  - 1. Observations of field growth rates, reproductive activities, and abundance of
      Aplysia calfiornica were made over a three-year period on Santa Catalina Island
      off southern California. 2. The mean weight of the population was found to vary
      with the location in which the animals were collected, presumably as a result of
      differing availability of food. 3. Seasonal weight differences were also
      apparent. In general, small specimens of A. californica appear between February
      and May. Mean weight reached a maximum between June and August. Considerable
      variability was encountered from year to year. 4. Tagging and recapture showed
      that growth rates reached a maximum in the spring just prior to breeding. The
      rate decreased thereafter until weight loss was experienced in August and
      September. 5. A. californica was usually most abundant in the spring, with
      numbers decreasing during the summer. The animals almost completely disappeared
      during the months of October, November, and December with the exception of
      extremely small specimens found on algae. 6. Breeding activity was occasionally
      observed as early as April and reached its greatest intensity during July and
      August when at least 80% of the animals collected were in breeding aggregations.
      7. Histological examination of gonads showed maximum oocyte diameter between June
      and October, and minimum between January and March. 8. Data are consistent with
      an annual species whose extended summer breeding period is terminated by the
      death of mature individuals during the fall.

PMID- 29324029
TI  - SALT AND WATER BALANCE IN TWO MARINE SPIDER CRABS, LIBINIA EMARGINATA AND
      PUGETTIA PRODUCTA. II. APPARENT WATER PERMEABILITY.
AB  - 1. Estimates of osmotic water permeability suggest that Libinia emarginata [166
      ul/(g.hr.osmol)] is less permeable to water than Pugettia producta [338 ul/
      (g.hr.osmol)]. Data on tracer water exchange supports this conclusion and the
      differences in apparent permeability can be correlated with differences in
      habitat. 2. Short-term changes in D2O water exchange were examined in specimens
      of Carcinus maenas and Libinia emarginata. When these crabs were transferred from
      100 to 80% sea water, there was an initial reduction in k in (1/hr), the hourly
      water exchange fraction, of from 1.9 to 1.4 and from 5.8 to 4.3 in Carcinus and
      Libinia, respectively. In both crabs, the initial response to the dilute medium
      is similar; however, in Libinia, the reduction in k is transient while in
      Carcinus it is a long-term response. 3. Estimates of osmotic (Posm*) and
      diffusive (Pd*) water permeabilities for Carcinus, Libinia and Pugettia indicate
      that the ratio of Posm*/Pd* is about 2, which suggests that unstirred layers
      could have a major influence on tracer water movement in all of these crabs. It
      is proposed that the initial changes in k, which occur during adaptation to a
      dilute medium, are at least partly the result of an increase in thickness of the
      unstirred layers surrounding the gills, caused by a reduction in the flow of
      medium through the gill chamber.

PMID- 29324030
TI  - UPTAKE OF AMINO ACIDS BY MARINE POLYCHAETES UNDER ANOXIC CONDITIONS.
AB  - 1. The effect of anoxia on influx and net flux of amino acids from dilute
      solutions into two species of marine polychaetes was studied. 2. Rates of influx
      and net flux correspond quite closely at ambient concentrations greater than 10
      uM. Anoxic conditions, produced by incubating specimens of Marphysa and
      Pareurythoe in solutions containing 2 mM KCN or through which N2 was bubbled, did
      not affect the tight correspondence between influx and net flux, though rates
      were reduced by approximately 50%. 3. The effect of Po2 on influx and net flux
      was examined using a continuous flow system. Influx and net influx remained at
      control rates down to Po2' s 10 to 20% of air saturation values. 4. Comparisons
      of rates of net flux to measured values of O2 consumption indicate that these
      animals can acquire sufficient reduced carbon to account for their oxidative
      needs if their surfaces are exposed to amino acid levels on the order of 50 to 65
      uM. 5. Primary amines in the interstitial water of sediments in the immediate
      vicinity of populations of these worms averaged between 123 and 131 uM. 6.
      Marphysa and Pareurythoe live in habitats that are relatively rich in amino
      acids, and they possess transport systems capable of the net accumulation of
      these compounds at rates sufficient to provide a significant supplement to other
      forms of feeding. The uptake process continues during periods of anoxia, though
      its rate and overall contribution to metabolic requirements are reduced.

PMID- 29324031
TI  - PARTHENOGENESIS IN COPTOPTERYX VIRIDIS, GIGLIO TOS (1915) (DYCTIOPTERA,
      MANTIDAE).
AB  - Several years of observations of the behavior of the mantid Coptoteryx viridis
      suggested evidence of parthenogenesis in this species. C. viridis is a solitary,
      sedentary animal, where the female often kills the male before copulation takes
      place, and the average male adult life is half that of the female. Virgin females
      were reared in our laboratory from their hatching to the end of their lives;
      these laid oothecas. From these oothecas, parthenogenetic nymphs were born, all
      of the female sex and with a very low viability. The karyo-type of the non
      parthenogenetic individuals of this species was found to be XO-XX with a diploid
      number of 27 chromosomes for the male and 28 for the female. The autosomes were
      acrocentric or "t" type while the X chromosome was subtelocentric or "st" type,
      according to Levan's classification.

PMID- 29324032
TI  - DEVELOPMENTAL PATTERN AND ADAPTATIONS FOR REPRODUCTION IN NUCELLA CRASSILABRUM
      AND OTHER MURICACEAN GASTROPODS.
AB  - 1. Eggs of Nucella crassilabrum range from 204 to 293 um in diameter (mean = 240
      um). Only 6.6 to 7.9% are fertile; the remaining are ingested as nurse eggs. 2.
      Embryos metamorphose before hatching. Pre-hatching time ranges from 55 to 80 days
      according to seasonal temperature fluctuations. 3. Hatching size varies from 0.82
      to 1.3 mm, depending on number of nurse-eggs ingested per embryo (from 3 to 20).
      Number of fertile embryos per capsule (10 to 122) depends on capsule size. 4.
      Hatching type and hatching size shown by N. crassilabrum agree with those of
      other muricaceans living in similar habitat conditions. 5. Pre-hatching time and
      hatching size data of various muricaceans are analyzed to determine to what
      extent they influence embryonic mode of nutrition, namely the presence of nurse
      eggs or alternatively large and fertile self-sufficient eggs. Provision of nurse
      eggs for embryos is of common occurrence among intertidal muricaceans and this
      mode of nutrition seems to have been favored in such habitats to reduce
      developmental time. Providing the yolk as nurse-eggs seems also to contribute to
      a larger hatching size, as suggested by some subtidal muricaceans with such
      embryo support patterns.

PMID- 29324033
TI  - EARLY POST-METAMORPHIC GROWTH, BUDDING AND SPICULE FORMATION IN THE COMPOUND
      ASCIDIAN CYSTODYTES LOBATUS.
AB  - 1. The colonial ascidian Cystodytes lobatus has a long breeding season (at least
      6 months) and releases tadpoles sporadically throughout the day, indicating a
      long period of recruitment. 2. Tadpoles of C. lobatus were settled and reared in
      the laboratory in order to observe early growth, budding and spicule formation.
      3. Budding is preceded by the formation of a new stomach at the posterior end of
      the esophagus and fits Nakauchi's Type I budding pattern. 4. Spicule formation
      begins within 5 days after settlement. The spicules appear to form in a
      particular region at the anterior end of the abdomen and migrate over the abdomen
      to form a single or slightly overlapping layer embedded in a "tunic spicular
      lamina." This lamina lies between the common tunic and the zooid cavity and forms
      a spicular sac in the tunic surrounding but separated from the abdomen of each
      zooid. It stains especially heavily for sulfated acid mucopolysaccharide; the
      spicules are concluded to form by cellular action in this organic matrix. 5.
      There is great variation among zooids in the quantity of spicules formed. These
      differences are maintained in the buds, resulting in colonies in which all zooids
      either have few or many spicules, and are therefore probably genetic in origin.
      6. During budding the spicular sac becomes disrupted and appears to bud,
      resulting in a reallocation of the spicules to the buds and formation of separate
      spicular sacs around the abdomen of each bud. At budding there is apparently no
      disruption of bladder cell membranes in the tunic and no dissolution of spicules
      by the acids contained in the bladder cells.

PMID- 29324034
TI  - CHARACTERISTICS AND REGULATION OF FISSION ACTIVITY IN CLONAL CULTURES OF THE
      COSMOPOLITAN SEA ANEMONE, HALIPLANELLA LUCIAE (VERRILL).
AB  - 1. Permanent cultures of a clone of H. luciae from N. W. Florida were reared
      under different temperature and feeding regimes in order to identifiy and
      quantify parameters of asexual reproduction. 2. The principle components of
      fission activity include fission rate, a delay period following a mechanical
      disturbance, and periodic pulses of increased fission activity; all components
      are regulated by temperature and feeding frequency. 3. A distinction is made
      between fission rate including the delay period (k), and fission rate following
      the delay period (kadj). 4. Fission rates (kadj) ranged from 0.0162 (doubling
      time = 42.8 days) at 17 degrees  C to 0.0727 (doubling time = 9.5 days) at 26
      degrees  C. 5. Temperature is the foremost regulator of k; the greatest influence
      of feeding frequency was upon periodic pulses of fission activity. 6. Culture
      data indicate that recruitment in natural populations of this clone is restricted
      by seasonal temperature; below 20 degrees  C there is a sharp reduction in k. It
      is suggested that inhibition of k by temperatures below 20 degrees  C favors a
      transition from asexual to sexual reproduction. 7. The pulsatile, periodic
      character of fission activity is prominent in laboratory cultures, and suggests
      that such activity in natural habitats may have a phasic dependence upon tidal
      and photoperiodic cycles.

PMID- 29324035
TI  - LOCOMOTOR AND LIGHT RESPONSES OF LARVAE OF THE HORSESHOE CRAB, LIMULUS POLYPHEMUS
      (L.).
AB  - The horseshoe crab Limulus polyphemus lays its eggs on sandy beaches at the level
      of the highest high tide in the northeastern Gulf of Mexico, buried approximately
      18 cm below the surface. When they hatch, the larvae must move from the buried
      nest site into the marine environment. In the field, nests of larvae move to the
      sand surface and emerge at the spring high tide on the night of full moon. They
      may also be released by heavy surf associated with storms. No release occurs on
      the spring high tides associated with new moon. In the laboratory, larvae are
      seen to be nocturnally active, both under ambient and DD photoperiods. Activity
      peaks at times of full and new moons, and larvae are positively phototatic at all
      lunar phases except new moon. A model to account for observed field behavior in
      light of laboratory activity and light responses is presented.

PMID- 29324036
TI  - Entomological Opportunities and Challenges for Sustainable Viticulture in a
      Global Market.
AB  - Viticulture has experienced dramatic global growth in acreage and value. As the
      international exchange of goods has increased, so too has the market demand for
      sustainably produced products. Both elements redefine the entomological
      challenges posed to viticulture and have stimulated significant advances in
      arthropod pest control programs. Vineyard managers on all continents are
      increasingly combating invasive species, resulting in the adoption of novel
      insecticides, semiochemicals, and molecular tools to support sustainable
      viticulture. At the local level, vineyard management practices consider factors
      such as the surrounding natural ecosystem, risk to fish populations, and air
      quality. Coordinated multinational responses to pest invasion have been highly
      effective and have, for example, resulted in eradication of the moth Lobesia
      botrana from California vineyards, a pest found in 2009 and eradicated by 2016.
      At the global level, the shared pests and solutions for their suppression will
      play an increasing role in delivering internationally sensitive pest management
      programs that respond to invasive pests, climate change, novel vector and
      pathogen relationships, and pesticide restrictions.

PMID- 29324037
TI  - Health Hazards Associated with Arthropod Infestation of Stored Products.
AB  - Insects and mites are common inhabitants and accidental invaders of food,
      including durable commodities, and their presence can have both direct and
      indirect effects on human health. The most common direct effect is contamination
      of food with arthropod fragments and related contaminants, which may be
      allergenic or even carcinogenic. The most important indirect effect is that their
      presence can change the storage microenvironment, making durable products
      suitable for the rapid development of fungi and other microorganisms. Some of
      these fungi can produce toxins (e.g., aflatoxins) that endanger human health.
      Insects may actively or passively contribute to the spread of microorganisms,
      increasing product contamination, and they may host bacteria that have developed
      antibiotic resistance, contributing to their spread in food. Several species also
      may host, attract, or transmit tapeworms, predators, or parasitoids that may
      affect health. This review synthesizes research on these topics and suggests
      directions for future research.

PMID- 29324038
TI  - The Evolution and Metamorphosis of Arthropod Proteomics and Genomics.
AB  - This article presents an overview of the development of techniques for analyzing
      cuticular proteins (CPs), their transcripts, and their genes over the past 50
      years based primarily on experience in the laboratory of J.H. Willis. It
      emphasizes changes in the kind of data that can be gathered and how such data
      provided insights into the molecular underpinnings of insect metamorphosis and
      cuticle structure. It describes the techniques that allowed visualization of the
      location of CPs at both the anatomical and intracuticular levels and measurement
      of the appearance and deployment of transcripts from CP genes as well as what was
      learned from genomic and transcriptomic data. Most of the early work was done
      with the cecropia silkmoth, Hyalophora cecropia, and later work was with
      Anopheles gambiae.

PMID- 29324039
TI  - Phylogeny and Evolution of Neuropterida: Where Have Wings of Lace Taken Us?
AB  - The last 25 years of phylogenetic investigation into the three orders
      constituting the superorder Neuropterida-Raphidioptera, Megaloptera, and
      Neuroptera-have brought about a dramatic revision in our understanding of the
      evolution of lacewings, snakeflies, dobsonflies, and their diverse relatives.
      Phylogenetic estimations based on combined analyses of diverse data sources,
      ranging from adult and larval morphology to full mitochondrial genomic DNA, have
      begun to converge on similar patterns, many times in accordance with hypotheses
      put forth by Cyril Withycombe nearly a century ago. These data, in combination
      with information from the fossil record, have given a revised perspective on the
      historical evolution and classification of Neuropterida, necessitating an
      overhaul of their organization and providing focus and insight on fruitful future
      efforts for neuropterology.

PMID- 29324040
TI  - Neonicotinoids and Other Insect Nicotinic Receptor Competitive Modulators:
      Progress and Prospects.
AB  - Neonicotinoids (neonics) are remarkably effective as plant systemics to control
      sucking insects and for flea control on dogs and cats. The nitroimines
      imidacloprid, clothianidin, thiamethoxam, and dinotefuran are the leaders among
      the seven commercial neonics that also include the nitromethylene nitenpyram, the
      nitromethylene-derived cycloxaprid, and the cyanoimines acetamiprid and
      thiacloprid. Honey bees are highly sensitive to the nitroimines and
      nitromethylenes, but the cyanoimines are less toxic. All neonics are nicotinic
      acetylcholine receptor (nAChR) agonists with a common mode of action, target-site
      cross-resistance, and much higher potency on insect than mammalian nAChRs at
      defined binding sites. The structurally related sulfoximine sulfoxaflor and
      butenolide flupyradifurone are also nAChR agonists, and the mesoionic
      triflumezopyrim is a nAChR competitive modulator with little or no target-site
      cross-resistance. Some neonics induce stress tolerance in plants via salicylate
      associated systems. The neonics in general are readily metabolized and, except
      for pollinators, have favorable toxicological profiles.

PMID- 29324041
TI  - Preface: Valedictory from a Gadfly Grammarian.

PMID- 29324042
TI  - Mosquito Immunobiology: The Intersection of Vector Health and Vector Competence.
AB  - As holometabolous insects that occupy distinct aquatic and terrestrial
      environments in larval and adult stages and utilize hematophagy for nutrient
      acquisition, mosquitoes are subjected to a wide variety of symbiotic
      interactions. Indeed, mosquitoes play host to endosymbiotic, entomopathogenic,
      and mosquito-borne organisms, including protozoa, viruses, bacteria, fungi,
      fungal-like organisms, and metazoans, all of which trigger and shape innate
      infection-response capacity. Depending on the infection or interaction, the
      mosquito may employ, for example, cellular and humoral immune effectors for
      septic infections in the hemocoel, humoral infection responses in the midgut
      lumen, and RNA interference and programmed cell death for intracellular
      pathogens. These responses often function in concert, regardless of the infection
      type, and provide a robust front to combat infection. Mosquito-borne pathogens
      and entomopathogens overcome these immune responses, employing avoidance or
      suppression strategies. Burgeoning methodologies are capitalizing on this
      concerted deployment of immune responses to control mosquito-borne disease.

PMID- 29324043
TI  - Tritrophic Interactions Mediated by Herbivore-Induced Plant Volatiles:
      Mechanisms, Ecological Relevance, and Application Potential.
AB  - Tritrophic interactions between plants, herbivores, and their natural enemies are
      an integral part of all terrestrial ecosystems. Herbivore-induced plant volatiles
      (HIPVs) play a key role in these interactions, as they can attract predators and
      parasitoids to herbivore-attacked plants. Thirty years after this discovery, the
      ecological importance of the phenomena is widely recognized. However, the primary
      function of HIPVs is still subject to much debate, as is the possibility of using
      these plant-produced cues in crop protection. In this review, we summarize the
      current knowledge on the role of HIPVs in tritrophic interactions from an
      ecological as well as a mechanistic perspective. This overview focuses on the
      main gaps in our knowledge of tritrophic interactions, and we argue that filling
      these gaps will greatly facilitate efforts to exploit HIPVs for pest control.

PMID- 29324044
TI  - The Management of Insect Pests in Australian Cotton: An Evolving Story.
AB  - The Australian cotton industry progressively embraced integrated pest management
      (IPM) to alleviate escalating insecticide resistance issues. A systems IPM
      approach was used with core principles that were built around pest
      ecology/biology and insecticide resistance management; together, these were
      integrated into a flexible, year-round approach that facilitated easy
      incorporation of new science, strategies, and pests. The approach emphasized both
      strategic and tactical elements to reduce pest abundance and rationalize
      decisions about pest control, with insecticides as a last resort. Industry
      involvement in developing the approach was vital to embedding IPM within the
      farming system. Adoption of IPM was facilitated by the introduction of Bt cotton,
      availability of selective insecticides, economic validation, and an industry-wide
      extension campaign. Surveys indicate IPM is now embedded in industry, confirming
      the effectiveness of an industry-led, backed-by-science approach. The amount of
      insecticide active ingredient applied per hectare against pests has also declined
      dramatically. Though challenges remain, pest management has transitioned from
      reactively attempting to eradicate pests from fields to proactively managing them
      year-round, considering the farm within the wider landscape.

PMID- 29324045
TI  - Neuroparasitology of Parasite-Insect Associations.
AB  - Insect behavior can be manipulated by parasites, and in many cases, such
      manipulation involves the central and peripheral nervous system.
      Neuroparasitology is an emerging branch of biology that deals with parasites that
      can control the nervous system of their host. The diversity of parasites that can
      manipulate insect behavior ranges from viruses to macroscopic worms and also
      includes other insects that have evolved to become parasites (notably, parasitic
      wasps). It is remarkable that the precise manipulation observed does not require
      direct entry into the insect brain and can even occur when the parasite is
      outside the body. We suggest that a spatial view of manipulation provides a
      holistic approach to examining such interactions. Integration across approaches
      from natural history to advanced imaging techniques, omics, and experiments will
      provide new vistas in neuroparasitology. We also suggest that for researchers
      interested in the proximate mechanisms of insect behaviors, studies of parasites
      that have evolved to control such behavior is of significant value.

PMID- 29324046
TI  - Gustatory Processing in Drosophila melanogaster.
AB  - The ability to identify nutrient-rich food and avoid toxic substances is
      essential for an animal's survival. Although olfaction and vision contribute to
      food detection, the gustatory system acts as a final checkpoint control for food
      acceptance or rejection. The vinegar fly Drosophila melanogaster tastes many of
      the same stimuli as mammals and provides an excellent model system for
      comparative studies of taste detection. The relative simplicity of the fly brain
      and behaviors, along with the molecular genetic and functional approaches
      available in this system, allow the examination of gustatory neural circuits from
      sensory input to motor output. This review discusses the molecules and cells that
      detect taste compounds in the periphery and the circuits that process taste
      information in the brain. These studies are providing insight into how the
      detection of taste compounds regulates feeding decisions.

PMID- 29324047
TI  - The Discovery of Arthropod-Specific Viruses in Hematophagous Arthropods: An Open
      Door to Understanding the Mechanisms of Arbovirus and Arthropod Evolution?
AB  - The discovery of an odd virus from hematophagous arthropods 40 years ago by
      Stollar and Thomas described cell fusing agent virus in cells derived from Aedes
      aegypti mosquitoes. Then came the report of Kamiti River virus from Ae.
      macintoshi in 1999, followed by worldwide reports of the discovery of other
      viruses of mosquitoes, ticks, and midges that replicate only in arthropods and
      not in vertebrates or in vertebrate cells. These viruses (now totaling at least
      64 published) have genomes analogous to viruses in various families that include
      arboviruses and nonarboviruses. It is likely that some of these viruses have been
      insufficiently studied and may yet be shown to infect vertebrates. However, there
      is no doubt that the vast majority are restricted to arthropods alone and that
      they represent a recently recognized clade. Their biology, modes of transmission,
      worldwide distribution (some have been detected in wild-caught mosquitoes in both
      Asia and the United States, for example), molecular characteristics of their
      genomes, and potential for becoming vertebrate pathogens, or at least serving as
      virus reservoirs, are fascinating and may provide evidence useful in
      understanding virus evolution. Because metagenomics studies of arthropods have
      shown that arthropod genomes are the sources of arthropod virus genomes, further
      studies may also provide insights into the evolution of arthropods. More
      recently, others have published excellent papers that briefly review discoveries
      of arthropod viruses and that characterize certain genomic peculiarities, but, to
      now, there have been no reviews that encompass all these facets. We therefore
      anticipate that this review is published at a time and in a manner that is
      helpful for both virologists and entomologists to make more sense and
      understanding of this recently recognized and obviously important virus group.
      This review focuses specifically on arthropod viruses in hematophagous
      arthropods.

PMID- 29324048
TI  - Peer Observation of Rounds Leads to Collegial Discussion of Teaching.
AB  - PROBLEM: Faculty in the Division of Hospital Medicine provide most of the
      clinical teaching for learners at our institution. The majority of these faculty
      are Assistant Professors with limited formal instruction in clinical teaching.
      Previous Divisional strategies to improve clinical teaching ability included
      discussion of effective teaching behaviors, developing written expectations for
      teaching faculty, and instituting seminars on effective clinical teaching.
      Heretofore, the Division had not utilized a direct observation exercise.
      INTERVENTION: We developed a direct observation exercise to encourage discussion
      of teaching techniques and contemplation of change. Using a social learning
      model, we developed a peer-to-peer observation followed by a nonevaluative
      discussion. We created a tool for describing teaching behaviors in 5 domains that
      were similar to or different from the usual behavior of the observing peer:
      learner presentations, team leadership, bedside teaching, professionalism, and
      other. After the observation, the observing and observed faculty met to discuss
      observed teaching behaviors. Both faculty members discussed and then recorded any
      teaching behaviors that they planned to adopt or change. CONTEXT: We implemented
      this intervention in a 22-member Academic Division of Hospital Medicine at a
      tertiary care medical center in the United States. A high proportion were junior
      faculty and graduates of our residency program. OUTCOME: We reviewed records of
      28 of 31 observations that were completed during the initial 9-month period of
      implementation and later surveyed faculty. The exercise resulted in planned
      changes in teaching behaviors that included instituting new methods to improve
      teaching team leadership, triaging of patients seen on rounds, faculty behaviors
      during oral presentations, giving real-time feedback, use of technology and
      humor, demonstrating physical examination findings, and modeling professional
      behaviors. Faculty later reported adoption of new teaching behaviors that were
      important to them. LESSONS LEARNED: This exercise was easily implemented,
      resulted in planned changes by both observed and observing peers, and resulted in
      widespread adoption of some specific teaching behaviors. The most commonly
      planned change dealt with team leadership or organizational issues. When given
      the freedom to choose, junior faculty were more likely to observe senior faculty.

PMID- 29324050
TI  - The Roles of Adjuvant Supplements in Colorectal Cancer Patients on Chemotherapy -
      Reaping Benefits from Metabolic Crosstalk.
AB  - The prevalence of colorectal cancer (CRC) is on a steady rise over the years,
      with the World Health Organization (WHO) reporting CRC as the fourth leading
      cause of cancer-related death worldwide. While treatment modalities may differ in
      accordance to the staging and severity of the disease itself, chemotherapy is
      almost unavoidable in most cases. Though effective in its mode of action,
      chemotherapy is commonly associated with undesirable side effects that negatively
      affects the patient in terms of quality of life, and in some cases may actually
      interfere with their treatment regimens, thus escalating to poor prognosis.
      Gastrointestinal disturbances is a major side effect of chemotherapy and in CRC,
      gastrointestinal disturbances may be further aggravated and grave in nature
      mainly due to the affected site, being the gastrointestinal tract. The use of
      complementary therapies as adjuncts to alleviate the side effects of chemotherapy
      in CRC patients is gaining prominence with dietary supplements being the most
      commonly employed adjunct. Some of the frequently used dietary supplements for
      CRC patients are probiotics, omega-3 fatty acid and glutamine. The successful
      crosstalk between these dietary supplements with important metabolic pathways is
      crucial in the alleviation of chemotherapy side effects.

PMID- 29324049
TI  - Extreme Response Style and the Measurement of Intra-Individual Variability in
      Affect.
AB  - Extreme response style (ERS) has the potential to bias the measurement of intra
      individual variability in psychological constructs. This paper explores such bias
      through a multilevel extension of a latent trait model for modeling response
      styles applied to repeated measures rating scale data. Modeling responses to
      multi-item scales of positive and negative affect collected from smokers at
      clinic visits following a smoking cessation attempt revealed considerable ERS
      bias in the intra-individual sum score variances. In addition, simulation studies
      suggest the magnitude and direction of bias due to ERS is heavily dependent on
      the mean affect level, supporting a model-based approach to the study and control
      of ERS effects. Application of the proposed model-based adjustment is found to
      improve intra-individual variability as a predictor of smoking cessation.

PMID- 29324051
TI  - Anti-IL-8 antibody potentiates the effect of exogenous surfactant in respiratory
      failure caused by meconium aspiration.
AB  - AIM: Meconium aspiration syndrome (MAS) is life-threatening respiratory failure
      of newborns which can be treated by exogenous surfactant. In response to
      meconium, increased levels of chemokine IL-8 (CXCL8) stimulate massive neutrophil
      infiltration of the lungs. Local accumulation and activation of neutrophils, on
      going inflammation, lung edema, and oxidative damage contribute to inactivation
      of endogenous and therapeutically given surfactants. Therefore, we have
      hypothesized that addition of monoclonal anti-IL-8 antibody into exogenous
      surfactant can mitigate the neutrophil-induced local injury and the secondary
      surfactant inactivation and may finally result in improvement of respiratory
      functions. METHODS: New Zealand rabbits with intratracheal meconium-induced
      respiratory failure (meconium 25 mg/ml, 4 ml/kg) were divided into three groups:
      untreated (M), surfactant-treated (M + S), and treated with combination of
      surfactant and anti-IL-8 antibody (M + S + anti-IL-8). Surfactant therapy
      consisted of two lung lavages with diluted porcine surfactant Curosurf (10 ml/kg,
      5 mg phospholipids (PL)/ml) followed by undiluted Curosurf (100 mg PL/kg)
      delivered by means of asymmetric high-frequency jet ventilation (f. 300/min, Ti
      20%). In M + S + anti-IL-8 group, anti-IL-8 antibody (100 ug/kg) was added
      directly to Curosurf dose. Animals were oxygen-ventilated for additional 5 h,
      respiratory parameters were measured regularly. Subsequently, cell counts in
      bronchoalveolar lavage fluid (BAL), lung edema formation, oxidative damage,
      levels of interleukins (IL)-1beta and IL-6 in the lung homogenate were evaluated.
      RESULTS: Surfactant instillation significantly improved lung function. Addition
      of anti-IL-8 to surfactant further improved gas exchange and ventilation
      efficiency and had longer-lasting effect than surfactant-only therapy. Combined
      treatment showed the trend to reduce neutrophil count in BAL fluid, local
      oxidative damage, and levels of IL-1beta and IL-6 more effectively than
      surfactant-alone, however, these differences were not significant. CONCLUSION:
      Addition of anti-IL-8 antibody to surfactant could potentiate the efficacy of
      Curosurf on the gas exchange in experimental model of MAS.

PMID- 29324052
TI  - The expression profile of Claudin family members in the developing mouse lung and
      expression alterations resulting from exposure to secondhand smoke (SHS).
AB  - Claudins are tight junctional proteins implicated in cell polarity and epithelial
      barrier maintenance. Claudin misregulation adversely impacts developmental
      aspects of cell differentiation and proliferation. The current research evaluated
      transcriptional expression for Claudins 1-11 and 18 in the developing murine lung
      at embryonic days (E) 14.5, 16.5, and 18.5 and at post-natal day (PN) 3 and PN15.
      Mouse lungs were also assessed by immunohistochemical analysis to qualitatively
      evaluate Claudin protein expression. Pregnant dams were further exposed to
      secondhand smoke (SHS) from embryonic day (E)15.5 to 18.5 and Claudin mRNA was
      immediately screened in pup lungs. Other than Claudin-6, mRNA expression patterns
      for Claudin family members tended to decrease at E16.5, increase at E18.5, and
      decrease again at PN3 before reaching a peak of expression at PN15. Claudin-6
      mRNA expression decreased through gestation and into post-natal periods.
      Immunohistochemical profiling implicated a subset of Claudins as plausible
      orchestrators of proximal vs. distal lung barrier establishment. Assessment of
      Claudin mRNA expression at E18.5 following SHS exposure revealed a significant
      reduction in transcription for all Claudins except Claudin-18 (no change). These
      data support the need for further studies using gene targeted mice that knock
      in/out specific Claudins so that precise functions in the normal and diseased
      lung can be determined.

PMID- 29324053
TI  - Systematic Review Methodology for the Fatigue in Emergency Medical Services
      Project.
AB  - BACKGROUND: Guidance for managing fatigue in the Emergency Medical Services (EMS)
      setting is limited. The Fatigue in EMS Project sought to complete multiple
      systematic reviews guided by seven explicit research questions, assemble the best
      available evidence, and rate the quality of that evidence for purposes of
      producing an Evidence Based Guideline (EBG) for fatigue risk management in EMS
      operations. METHODS: We completed seven systematic reviews that involved searches
      of six databases for literature relevant to seven research questions. These
      questions were developed a priori by an expert panel and framed in the
      Population, Intervention, Comparison, and Outcome (PICO) format and pre
      registered with PROSPERO. Our target population was defined as persons 18 years
      of age and older classified as EMS personnel or similar shift worker groups. A
      panel of experts selected outcomes for each PICO question as prescribed by the
      Grading of Recommendations, Assessment, Development, and Evaluation (GRADE)
      methodology. We pooled findings, stratified by study design (experimental vs.
      observational) and presented results of each systematic review in narrative and
      quantitative form. We used meta-analyses of select outcomes to generate pooled
      effects. We used the GRADE methodology and the GRADEpro software to designate a
      quality of evidence rating for each outcome. RESULTS: We present the results for
      each systematic review in accordance with the Preferred Reporting Items for
      Systematic reviews and Meta-Analyses (PRISMA). More than 38,000 records were
      screened across seven systematic reviews. The median, minimum, and maximum inter
      rater agreements (Kappa) between screeners for our seven systematic reviews were
      0.66, 0.49, and 0.88, respectively. The median, minimum, and maximum number of
      records retained for the seven systematic reviews was 13, 1, and 100,
      respectively. We present key findings in GRADE Evidence Profile Tables in
      separate publications for each systematic review. CONCLUSIONS: We describe a
      protocol for conducting multiple, simultaneous systematic reviews connected to
      fatigue with the goal of creating an EBG for fatigue risk management in the EMS
      setting. Our approach may be informative to others challenged with the creation
      of EBGs that address multiple, inter-related systematic reviews with overlapping
      outcomes.

PMID- 29324054
TI  - Bayesian Diagnostics of Hidden Markov Structural Equation Models with Missing
      Data.
AB  - Cocaine is a type of drug that functions to increase the availability of the
      neurotransmitter dopamine in the brain. However, cocaine dependence or abuse is
      highly related to an increased risk of psychiatric disorders and deficits in
      cognitive performance, attention, and decision-making abilities. Given the
      chronic and persistent features of drug addiction, the progression of abstaining
      from cocaine often evolves across several states, such as addiction to, moderate
      dependence on, and swearing off cocaine. Hidden Markov models (HMMs) are well
      suited to the characterization of longitudinal data in terms of a set of
      unobservable states, and have increasingly been used to uncover the dynamic
      heterogeneity in progressive diseases or activities. However, the existence of
      outliers or influential points may misidentify the hidden states and distort the
      associated inference. In this study, we develop a Bayesian local influence
      procedure for HMMs with latent variables in the presence of missing data. The
      proposed model enables us to investigate the dynamic heterogeneity of
      multivariate longitudinal data, reveal how the interrelationships among latent
      variables change from one state to another, and simultaneously conduct
      statistical diagnosis for the given data, model assumptions, and prior inputs. We
      apply the proposed procedure to analyze a dataset collected by the UCLA center
      for advancing longitudinal drug abuse research. Several outliers or influential
      points that seriously influence estimation results are identified and removed.
      The proposed procedure also discovers the effects of treatment and individuals'
      psychological problems on cocaine use behavior and delineates their dynamic
      changes across the cocaine-addiction states.

PMID- 29324055
TI  - Bayesian PTSD-Trajectory Analysis with Informed Priors Based on a Systematic
      Literature Search and Expert Elicitation.
AB  - There is a recent increase in interest of Bayesian analysis. However, little
      effort has been made thus far to directly incorporate background knowledge via
      the prior distribution into the analyses. This process might be especially useful
      in the context of latent growth mixture modeling when one or more of the latent
      groups are expected to be relatively small due to what we refer to as limited
      data. We argue that the use of Bayesian statistics has great advantages in
      limited data situations, but only if background knowledge can be incorporated
      into the analysis via prior distributions. We highlight these advantages through
      a data set including patients with burn injuries and analyze trajectories of
      posttraumatic stress symptoms using the Bayesian framework following the steps of
      the WAMBS-checklist. In the included example, we illustrate how to obtain
      background information using previous literature based on a systematic literature
      search and by using expert knowledge. Finally, we show how to translate this
      knowledge into prior distributions and we illustrate the importance of conducting
      a prior sensitivity analysis. Although our example is from the trauma field, the
      techniques we illustrate can be applied to any field.

PMID- 29324057
TI  - Evidence-Based Guidelines for Fatigue Risk Management in Emergency Medical
      Services: A Significant Step Forward and a Model for Other High-Risk Industries.

PMID- 29324056
TI  - Cardiopulmonary effects induced by occupational exposure to titanium dioxide
      nanoparticles.
AB  - Although some toxicological studies have reported that exposure to titanium
      dioxide nanoparticles (nano-TiO2) may elicit adverse cardiopulmonary effects,
      related data collected from human are currently limited. The purpose of this
      study is to explore cardiopulmonary effects among workers who were exposed to
      nano-TiO2 and to identify biomarkers associated with exposure. A cross-sectional
      study was conducted in a nano-TiO2 manufacturing plant in eastern China. Exposure
      assessment and characterization of TiO2 particles were performed in a packaging
      workshop. Physical examination and possible biomarkers for cardiopulmonary
      effects were examined among 83 exposed workers and 85 controls. In packaging
      workshop, the total mass concentration of particles was 3.17 mg/m3. The mass
      concentration of nanoparticles was 1.22 mg/m3 accounting for 39% of the total
      mass. Lung damage markers (SP-D and pulmonary function), cardiovascular disease
      markers (VCAM-1, ICAM-1, LDL, and TC), oxidative stress markers (SOD and MDA),
      and inflammation markers (IL-8, IL-6, IL-1beta, TNF-alpha, and IL-10) were
      associated with occupational exposure to nano-TiO2. Among those markers, SP-D
      showed a time (dose)-response pattern within exposed workers. The data strongly
      suggest that nano-TiO2 could contribute, at least in part, to the cardiopulmonary
      effects observed in workers. The studied markers and pulmonary function tests may
      be useful in health surveillance for workers exposed to nanomaterials.

PMID- 29324058
TI  - Evidence-Based Guidelines for Fatigue Risk Management in Emergency Medical
      Services: A Step in the Right Direction Toward Better Sleep Health.

PMID- 29324059
TI  - Effect of Fatigue Training on Safety, Fatigue, and Sleep in Emergency Medical
      Services Personnel and Other Shift Workers: A Systematic Review and Meta
      Analysis.
AB  - BACKGROUND: Fatigue training may be an effective way to mitigate fatigue-related
      risk. We aimed to critically review and synthesize existing literature on the
      impact of fatigue training on fatigue-related outcomes for Emergency Medical
      Services (EMS) personnel and similar shift worker groups. METHODS: We performed a
      systematic literature review for studies that tested the impact of fatigue
      training of EMS personnel or similar shift workers. Outcomes of interest included
      personnel safety, patient safety, personnel performance, acute fatigue,
      indicators of sleep duration and quality, indicators of long-term health (e.g.,
      cardiovascular disease), and burnout/stress. A meta-analysis was performed to
      determine the impact of fatigue training on sleep quality. RESULTS: Of the 3,817
      records initially identified for review, 18 studies were relevant and examined
      fatigue training in shift workers using an experimental or quasi-experimental
      design. Fatigue training improved patient safety, personal safety, and ratings of
      acute fatigue and reduced stress and burnout. A meta-analysis of five studies
      showed improvement in sleep quality (Fixed Effects SMD -0.87; 95% CI -1.05 to 
      0.69; p < 0.00001; Random Effects SMD -0.80; 95% CI -1.72, 0.12; p < 0.00001).
      CONCLUSIONS: Reviewed literature indicated that fatigue training improved safety
      and health outcomes in shift workers. Further research is required to identify
      the optimal components of fatigue training programs to maximize the beneficial
      outcomes.

PMID- 29324060
TI  - Proposed Performance Measures and Strategies for Implementation of the Fatigue
      Risk Management Guidelines for Emergency Medical Services.
AB  - BACKGROUND: Performance measures are a key component of implementation,
      dissemination, and evaluation of evidence-based guidelines (EBGs). We developed
      performance measures for Emergency Medical Services (EMS) stakeholders to enable
      the implementation of guidelines for fatigue risk management in the EMS setting.
      METHODS: Panelists associated with the Fatigue in EMS Project, which was
      supported by the National Highway Traffic Safety Administration (NHTSA), used an
      iterative process to develop a draft set of performance measures linked to 5
      recommendations for fatigue risk management in EMS. We used a cross-sectional
      survey design and the Content Validity Index (CVI) to quantify agreement among
      panelists on the wording and content of draft measures. An anonymous web-based
      tool was used to solicit the panelists' perceptions of clarity and relevance of
      draft measures. Panelists rated the clarity and relevance separately for each
      draft measure on a 4-point scale. CVI scores >=0.78 for clarity and relevance
      were specified a priori to signify agreement and completion of measurement
      development. RESULTS: Panelists judged 5 performance measures for fatigue risk
      management as clear and relevant. These measures address use of fatigue and/or
      sleepiness survey instruments, optimal duration of shifts, access to caffeine as
      a fatigue countermeasure, use of napping during shift work, and the delivery of
      education and training on fatigue risk management for EMS personnel. Panelists
      complemented performance measures with suggestions for implementation by EMS
      agencies. CONCLUSIONS: Performance measures for fatigue risk management in the
      EMS setting will facilitate the implementation and evaluation of the EBG for
      Fatigue in EMS.

PMID- 29324061
TI  - The Prediction of Deterioration of Nutritional Status during Chemoradiation
      Therapy in Patients with Esophageal Cancer.
AB  - Patients with esophageal cancer are at high risk of developing malnutrition
      during neoadjuvant chemoradiation therapy (CRT), which in turn is associated with
      postoperative morbidity. The aim of the study is to explore whether parameters of
      a complete pre-treatment nutritional status may predict deterioration of
      nutritional status during CRT in patients with esophageal cancer. In this
      prospective cohort study, 101 patients with esophageal cancer treated with CRT
      were included. Data of patient characteristics, tumor classification, performance
      score, %weight change, body mass index, fat (free) mass index, phase angle,
      handgrip strength, energy- and protein intake, and use of (additional) dietary
      supplements were collected. A prediction model was constructed to identify
      predictive parameters for deterioration in nutritional status (defined as weight
      loss of >5% and/or decline in fat free mass of >=1.4 kg) during CRT. Nutritional
      status deteriorated in 49 patients (49%) during CRT. The only predictor for
      deterioration in nutritional status was fat free mass index (OR 1.21 (90% CI:
      1.03 - 1.42)). Patients with a higher fat free mass index are at increased risk
      of deterioration in nutrition status during CRT. Results suggest that all
      patients should be carefully supervised during CRT, regardless of their
      nutritional status before start of CRT.

PMID- 29324062
TI  - Four-day pulse of sodium cromoglycate modulates pulmonary vessel wall remodeling
      during 21-day hypoxia in rats.
AB  - AIM OF THE STUDY: Remodeling of pulmonary resistance arteries in rats due to 4
      day hypoxia could be successfully suppressed by sodium cromoglycate. In this
      study, we tested the difference in the suppression between two distinct time
      patterns of cromoglycate administration during 21-day hypoxia. In the experiment,
      we focused on some details in both smooth muscle cells and extracellular matrix
      of pulmonary arterial walls. METHODS: During 21-day hypoxia, rats were treated
      with sodium cromoglycate either in the first four days or in the last four days.
      The first four days were chosen to test efficiency of an initial pulse of
      cromoglycate to suppress pulmonary vascular remodeling. The last four-day
      administration tested possibility to block remodeling post hoc. RESULTS: Initial
      pulse reduced and modified remodeling in all levels of pulmonary arteries, which
      comprises neomuscularization of prealveolar arteries, asymmetrical hypertrophy of
      tunica media in muscular pulmonary arteries and hypertrophy of tunica media and
      tunica adventitia in large conduit arteries. Terminal pulse had only negligible
      effect. CONCLUSIONS: Only the initial cromoglycate therapy led to significant
      morphological suppression of remodeling. We therefore assume important role of
      initial remodeling influencing during long time hypoxia experiment.

PMID- 29324063
TI  - Granulomatous lung inflammation is nanoparticle type-dependent.
AB  - BACKGROUND: Nanoparticles are increasingly suspected as a strong etiologic factor
      of granuloma formation. AIM OF THE STUDY: The aim of our study was to compare
      lung inflammatory response and histology changes following exposure of mice to
      two widely used nanoparticles: carbon nanotubes (MWCNT) and cadmium-based
      nanoparticles (QDOT705) in an attempt to better our understanding of
      granulomatous inflammation. MATERIALS AND METHODS: Various groups of mice were
      included: control mice and mice that were intranasally instilled with QDOT or
      MWCNT. At defined time points post-challenge, bronchoalveolar lavages (BALs) and
      lung tissues were collected to study inflammatory and histologic changes.
      RESULTS: Analyses of lung BAL fluids and tissues of nanoparticles-challenged mice
      in comparison to controls found: (1) increased cellularity in BALs, (2) increase
      of total protein concentration, LDH activity and proteolytic activity in BALs;
      (3) patchy granulomas, (4) macrophages, CD3 +/- T, Treg and B cell infiltration
      in granulomatous areas; and (5) altered regulation of key inflammatory mediators
      and receptors. Importantly, these changes were nanoparticle type-dependent.
      CONCLUSION: Our work enhances understanding of nanoparticles-induced lung
      inflammatory and histological changes that result in granuloma formation. We
      provide compelling evidence that not only exposure to nanoparticles leads to
      granulomatous lung inflammation, but the severity of this latter is nanostructure
      type-dependent. Of importance, while nanotechnology has the potential to
      revolutionize various fields including medicine, nanoparticles form the potential
      for an entirely new lung health risk that it is necessary to take seriously into
      consideration by setting up and/or reinforcing adequate safety measures.

PMID- 29324065
TI  - Fatigue Risk Management in High-Risk Environments: A Call to Action.

PMID- 29324064
TI  - Interchangeability of Results From Computerized and Traditional Administration of
      the BIDR: Convenience Can Match Reality.
AB  - Although interchangeability of results across computer and paper modes of
      administration is commonly assumed, recent meta-analyses and individual studies
      continue to reveal mean differences in scores for measures of socially desirable
      responding (SDR). Results from these studies have also failed to include new
      methods of scoring and crucial aspects of scaling, reliability, validity, and
      administration emphasized in professional standards for assessment that are
      essential in establishing equivalence. We addressed these shortcomings in a
      comprehensive, repeated measures investigation for 6 ways of scoring the Balanced
      Inventory of Desirable Responding (BIDR), one of the most frequently administered
      companion measures of SDR in research and practice. Results for many previously
      unexamined, standards-driven aspects of scaling, reliability, and validity
      strongly supported the interchangeability of scores across modes of
      administration. Computer questionnaires also took considerably less time to
      complete and were overwhelmingly favored by respondents in relation to physical
      characteristics of the measures, appraisals of the the assessment experience, and
      perceived quality of information obtained. Collectively, these results highlight
      the importance of following professional standards when constructing and
      administering computerized assessments and the evolution of computer technology
      in providing viable, effective, and accepted platforms for administering and
      scoring the BIDR in numerous ways.

PMID- 29324066
TI  - Systematic Review and Meta-analysis of the Effects of Caffeine in Fatigued Shift
      Workers: Implications for Emergency Medical Services Personnel.
AB  - BACKGROUND: Emergency Medical Services (EMS) workers may experience fatigue as a
      consequence of shift work. We reviewed the literature to determine the impact of
      caffeine as a countermeasure to fatigue in EMS personnel and related shift
      workers. METHODS: We employed the GRADE methodology to perform a systematic
      literature review and search multiple databases for research that examined the
      impact of caffeine on outcomes of interest, such as patient and EMS personnel
      safety. For selected outcomes, we performed a meta-analysis of pooled data and
      reported the pooled effect in the form of a Standardized Mean Difference (SMD)
      with corresponding 95% confidence intervals. RESULTS: There are no studies that
      investigate caffeine use and its effects on EMS workers or on patient safety.
      Four of 8 studies in shift workers showed that caffeine improved psychomotor
      vigilance, which is important for performance. Caffeine decreased the number of
      lapses on a standardized test of performance [SMD = 0.75 (95% CI: 0.30 to 1.19),
      p = 0.001], and lessened the slowing of reaction time at the end of shifts [SMD =
      0.52 (95% CI: 0.19 to 0.85); p = 0.002]. Finally, 2 studies reported that
      caffeine reduced sleep quality and sleep duration. CONCLUSIONS: Although the
      quality of evidence was judged to be low to moderate, when taken together, these
      studies demonstrate that caffeine can improve psychomotor performance and
      vigilance. However, caffeine negatively affects sleep quality and sleep duration.
      More systematic, randomized studies need to be conducted in EMS workers in order
      to address the critical outcomes of health and safety of EMS personnel and
      patients. The risk/benefit ratio of chronic caffeine use in shift workers is
      currently unknown.

PMID- 29324067
TI  - MAO inhibitors and their wider applications: a patent review.
AB  - INTRODUCTION: Monoamine oxidase (MAO) inhibitors, after the initial 'golden age',
      are currently used as third-line antidepressants (selective MAO-A inhibitors) or
      clinically enrolled as co-adjuvants for neurodegenerative diseases (selective MAO
      B inhibitors). However, the research within this field is always increasing due
      to their pivotal role in modulating synaptic functions and monoamines metabolism.
      Areas covered: In this paper, MAO inhibitors (2015-2017) are disclosed ordering
      all the patents according to their chemical scaffold. Structure-activity
      relationships (SARs) are extrapolated for the most investigated chemotypes
      (coumarins, pyrazole/oxazepinones, (hetero)arylamides). 108 Compounds are divided
      into two main groups: newly synthesized molecules and naturally-occurring
      metabolites. Finally, new therapeutic options are outlined to ensure a more
      complete view on the potential of these inhibitors. Expert opinion: New proposed
      MAO inhibitors are endowed with a marked isoform selectivity, with innovative
      therapeutic potential toward other targets (gliomas, inflammation, muscle
      dystrophies, migraine, chronic pain, pseudobulbar affect), and with a promising
      ability to address multi-faceted pathologies such as Alzheimer's disease. The
      increasing number of patents is analyzed collecting data from 2002 to 2017.

PMID- 29324068
TI  - Reliability and Validity of Survey Instruments to Measure Work-Related Fatigue in
      the Emergency Medical Services Setting: A Systematic Review.
AB  - BACKGROUND: This study sought to systematically search the literature to identify
      reliable and valid survey instruments for fatigue measurement in the Emergency
      Medical Services (EMS) occupational setting. METHODS: A systematic review study
      design was used and searched six databases, including one website. The research
      question guiding the search was developed a priori and registered with the
      PROSPERO database of systematic reviews: "Are there reliable and valid
      instruments for measuring fatigue among EMS personnel?" (2016:CRD42016040097).
      The primary outcome of interest was criterion-related validity. Important
      outcomes of interest included reliability (e.g., internal consistency), and
      indicators of sensitivity and specificity. Members of the research team
      independently screened records from the databases. Full-text articles were
      evaluated by adapting the Bolster and Rourke system for categorizing findings of
      systematic reviews, and the rated data abstracted from the body of literature as
      favorable, unfavorable, mixed/inconclusive, or no impact. The Grading of
      Recommendations, Assessment, Development and Evaluation (GRADE) methodology was
      used to evaluate the quality of evidence. RESULTS: The search strategy yielded
      1,257 unique records. Thirty-four unique experimental and non-experimental
      studies were determined relevant following full-text review. Nineteen studies
      reported on the reliability and/or validity of ten different fatigue survey
      instruments. Eighteen different studies evaluated the reliability and/or validity
      of four different sleepiness survey instruments. None of the retained studies
      reported sensitivity or specificity. Evidence quality was rated as very low
      across all outcomes. CONCLUSIONS: In this systematic review, limited evidence of
      the reliability and validity of 14 different survey instruments to assess the
      fatigue and/or sleepiness status of EMS personnel and related shift worker groups
      was identified.

PMID- 29324069
TI  - Evidence-Based Guidelines for Fatigue Risk Management in Emergency Medical
      Services.
AB  - BACKGROUND: Administrators of Emergency Medical Services (EMS) operations lack
      guidance on how to mitigate workplace fatigue, which affects greater than half of
      all EMS personnel. The primary objective of the Fatigue in EMS Project was to
      create an evidence-based guideline for fatigue risk management tailored to EMS
      operations. METHODS: Systematic searches were conducted from 1980 to September
      2016 and guided by seven research questions framed in the Population,
      Intervention, Comparison, Outcome (PICO) framework. Teams of investigators
      applied inclusion criteria, which included limiting the retained literature to
      EMS personnel or similar shift worker groups. The expert panel reviewed summaries
      of the evidence based on the Grading of Recommendations, Assessment, Development
      and Evaluation (GRADE) methodology. The panel evaluated the quality of evidence
      for each PICO question separately, considered the balance between benefits and
      harms, considered the values and preferences of the targeted population, and
      evaluated the resource requirements/needs. The GRADE Evidence-to-Decision (EtD)
      Framework was used to prepare draft recommendations based on the evidence, and
      the Content Validity Index (CVI) was used to quantify the panel's agreement on
      the relevance and clarity of each recommendation. CVI scores for relevance and
      clarity were measured separately on a 1-4 scale to indicate consensus/agreement
      among panel members and conclusion of recommendation development. RESULTS: The
      EtD framework was applied to all 7 PICO questions, and the panel created 5
      recommendations. PICO1: The panel recommends using fatigue/sleepiness survey
      instruments to measure and monitor fatigue in EMS personnel. PICO2: The panel
      recommends that EMS personnel work shifts shorter than 24 hours in duration.
      PICO3: The panel recommends that EMS personnel have access to caffeine as a
      fatigue countermeasure. PICO4: The panel recommends that, EMS personnel have the
      opportunity to nap while on duty to mitigate fatigue. PICO5: The panel recommends
      that EMS personnel receive education and training to mitigate fatigue and fatigue
      related risks. The panel referenced insufficient evidence as the reason for
      making no recommendation linked to 2 PICO questions. CONCLUSIONS: Based on a
      review of the evidence, the panel developed a guideline with 5 recommendations
      for fatigue risk management in EMS operations.

PMID- 29324070
TI  - Does Implementation of Biomathematical Models Mitigate Fatigue and Fatigue
      related Risks in Emergency Medical Services Operations? A Systematic Review.
AB  - BACKGROUND: Work schedules like those of Emergency Medical Services (EMS)
      personnel have been associated with increased risk of fatigue-related impairment.
      Biomathematical modeling is a means of objectively estimating the potential
      impacts of fatigue on performance, which may be used in the mitigation of fatigue
      related safety risks. In the context of EMS operations, our objective was to
      assess the evidence in the literature regarding the effectiveness of using
      biomathematical models to help mitigate fatigue and fatigue-related risks.
      METHODS: A systematic review of the evidence evaluating the use of
      biomathematical models to manage fatigue in EMS personnel or similar shift
      workers was performed. Procedures proposed by the Grading of Recommendations,
      Assessment, Development, and Evaluation (GRADE) methodology were used to
      summarize and rate the certainty in the evidence. Potential bias attached to
      retained studies was documented using the Cochrane Collaboration's Risk of Bias
      tool for experimental studies. RESULTS: The literature search strategy, which
      focused on both EMS personnel and non-EMS shift workers, yielded n = 2,777 unique
      records. One paper, which investigated non-EMS shift workers, met inclusion
      criteria. As part of a larger effort, managers and dispatchers of a trucking
      operation were provided with monthly biomathematical model analyses of predicted
      fatigue in the driver workforce, and educated on how they could reduce predicted
      fatigue by means of schedule adjustments. The intervention showed a significant
      reduction in the number and cost of vehicular accidents during the period in
      which biomathematical modeling was used. The overall GRADE assessment of evidence
      quality was very low due to risk of bias, indirectness, imprecision, and
      publication bias. CONCLUSIONS: This systematic review identified no studies that
      investigated the impact of biomathematical models in EMS operations. Findings
      from one study of non-EMS shift workers were favorable toward use of
      biomathematical models as a fatigue mitigation scheduling aid, albeit with very
      low quality of evidence pertaining to EMS operations. We propose three focus
      areas of research priorities that, if addressed, could help better elucidate the
      utility and impact of biomathematical models as a fatigue-mitigation tool in the
      EMS environment.

PMID- 29324071
TI  - Effect of Task Load Interventions on Fatigue in Emergency Medical Services
      Personnel and Other Shift Workers: A Systematic Review.
AB  - BACKGROUND: Modifying the task load of Emergency Medical Services (EMS) personnel
      may mitigate fatigue, sleep quality and fatigue related risks. A review of the
      literature addressing task load interventions may benefit EMS administrators as
      they craft policies related to mitigating fatigue. We conducted a systematic
      review of the peer-reviewed literature to address the following question: "In EMS
      personnel, do task load interventions mitigate fatigue, mitigate fatigue-related
      risks, and/or improve sleep?" (PROSPERO 2016:CRD42016040114). METHODS: We
      performed a systematic review of the literature that described use of randomized
      controlled trials, quasi-experimental studies, and observational study designs.
      We retained and reviewed research that involved EMS personnel or similar shift
      worker groups 18 years of age and older. Studies of 'healthy volunteers' and non
      shift worker populations were excluded. Studies were included where the
      methodology of the study implied a theoretical framework of task load (or
      workload) affecting fatigue, and then fatigue related outcomes. Outcomes of
      interest included personnel safety, patient safety, personnel performance, acute
      fatigue, and cost to system. We used the Grading of Recommendations, Assessment,
      Development, and Evaluation (GRADE) methodology to summarize findings and assess
      quality of evidence from very low to high quality. RESULTS: The search strategy
      yielded 3,394 unique records resulting in 58 records included as potentially
      eligible. An additional 69 studies were reviewed in full following searches of
      bibliographies. We detected wide variation in the description and measurement of
      task load in the retained and excluded research. Among 127 potentially relevant
      studies reviewed in full, five were judged eligible. None of the retained studies
      reported findings germane to personnel safety, patient safety, or cost to system.
      We judged most studies to have serious or very serious risk of bias. CONCLUSIONS:
      The effect of task load interventions on fatigue, fatigue-related risks, and/or
      sleep quality was not estimable and the overall quality of evidence was judged
      low or very low. There was considerable heterogeneity in how task load was
      defined and measured.

PMID- 29324073
TI  - Rapid Improvement on a Temporal Attention Task within a Single Session of High
      frequency Transcranial Random Noise Stimulation.
AB  - This study explored the modulatory effects of high-frequency transcranial random
      noise stimulation (tRNS) on visual sensitivity during a temporal attention task.
      We measured sensitivity to different onset asynchronies during a temporal order
      judgment task as a function of active stimulation relative to sham. While
      completing the task, participants were stimulated bilaterally for 20 min over
      either the TPJ or the human middle temporal area. We hypothesized that tRNS over
      the TPJ, which is critical to the temporal attention network, would selectively
      increase cortical excitability and induce cognitive training-like effects on
      performance, perhaps more so in the left visual field [Matthews, N., & Welch, L.
      Left visual field attentional advantage in judging simultaneity and temporal
      order. Journal of Vision, 15, 1-13, 2015; Romanska, A., Rezlescu, C., Susilo, T.,
      Duchaine, B., & Banissy, M. J. High-frequency transcranial random noise
      stimulation enhances perception of facial identity. Cerebral Cortex, 25, 4334
      4340, 2015]. In Experiment 1, we measured the performance of participants who
      judged the order of Gabors temporally imbedded in flickering discs, presented
      with onset asynchronies ranging from -75 msec (left disc first) to +75 msec
      (right disc first). In Experiment 2, we measured whether each participant's
      temporal sensitivity increased with stimulation by using temporal offsets that
      the participant initially perceived as simultaneous. We found that parietal
      cortex stimulation temporarily increased sensitivity on the temporal order
      judgment task, especially in the left visual field. Stimulation over human middle
      temporal area did not alter cortical excitability in a way that affected
      performance. The effects were cumulative across blocks of trials for tRNS over
      parietal cortex but dissipated when stimulation ended. We conclude that single
      session tRNS can induce temporary improvements in behavioral sensitivity and that
      this shows promising insight into the relationship between cortical stimulation
      and neural plasticity.

PMID- 29324072
TI  - Alpha Oscillations during Incidental Encoding Predict Subsequent Memory for New
      "Foil" Information.
AB  - People can employ adaptive strategies to increase the likelihood that previously
      encoded information will be successfully retrieved. One such strategy is to
      constrain retrieval toward relevant information by reimplementing the
      neurocognitive processes that were engaged during encoding. Using EEG, we
      examined the temporal dynamics with which constraining retrieval toward semantic
      versus nonsemantic information affects the processing of new "foil" information
      encountered during a memory test. Time-frequency analysis of EEG data acquired
      during an initial study phase revealed that semantic compared with nonsemantic
      processing was associated with alpha decreases in a left frontal electrode
      cluster from around 600 msec after stimulus onset. Successful encoding of
      semantic versus nonsemantic foils during a subsequent memory test was related to
      decreases in alpha oscillatory activity in the same left frontal electrode
      cluster, which emerged relatively late in the trial at around 1000-1600 msec
      after stimulus onset. Across participants, left frontal alpha power elicited by
      semantic processing during the study phase correlated significantly with left
      frontal alpha power associated with semantic foil encoding during the memory
      test. Furthermore, larger left frontal alpha power decreases elicited by semantic
      foil encoding during the memory test predicted better subsequent semantic foil
      recognition in an additional surprise foil memory test, although this effect did
      not reach significance. These findings indicate that constraining retrieval
      toward semantic information involves reimplementing semantic encoding operations
      that are mediated by alpha oscillations and that such reimplementation occurs at
      a late stage of memory retrieval, perhaps reflecting additional monitoring
      processes.

PMID- 29324074
TI  - Synchronization of Electrophysiological Responses with Speech Benefits Syntactic
      Information Processing.
AB  - In auditory neuroscience, electrophysiological synchronization to low-level
      acoustic and high-level linguistic features is well established-but its
      functional purpose for verbal information transmission is unclear. Based on prior
      evidence for a dependence of auditory task performance on delta-band oscillatory
      phase, we hypothesized that the synchronization of electrophysiological responses
      at delta-band frequency to the speech stimulus serves to implicitly align neural
      excitability with syntactic information. The experimental paradigm of our
      auditory EEG study uniformly distributed morphosyntactic violations across
      syntactic phrases of natural sentences, such that violations would occur at
      points differing in linguistic information content. In support of our hypothesis,
      we found behavioral responses to morphosyntactic violations to increase with
      decreasing syntactic information content-in significant correlation with delta
      band phase, which had synchronized to our speech stimuli. Our findings indicate
      that rhythmic electrophysiological synchronization to the speech stream is a
      functional mechanism that may align neural excitability with linguistic
      information content, optimizing language comprehension.

PMID- 29324075
TI  - Screening of veterinary drug residues in food by LC-MS/MS. Background and
      challenges.
AB  - Regulatory agencies and government authorities have established maximum residue
      limits (MRL) in various food matrices of animal origin for supporting governments
      and food operators in the monitoring of veterinary drug residues in the food
      chain, and ultimately in the consumer's plate. Today, about 200 veterinary drug
      residues from several families, mainly with antibiotic, antiparasitic or
      antiinflammatory activities, are regulated in a variety of food matrices such as
      milk, meat or egg. This article provides a review of the regulatory framework in
      milk and muscle including data from Codex Alimentarius, Europe, the U.S.A.,
      Canada and China for about 220 veterinary drugs. The article also provides a
      comprehensive overview of the challenge for food control, and emphasizes the
      pivotal role of liquid chromatography-mass spectrometry (LC-MS), either in tandem
      with quadrupoles (LC-MS/MS) or high resolution MS (LC-HRMS), for ensuring an
      adequate consumer protection combined with an affordable cost. The capability of
      a streamlined LC-MS/MS platform for screening 152 veterinary drug residues in a
      broad range of raw materials and finished products is highlighted in a production
      line perspective. The rationale for a suite of four methods intended to achieve
      appropriate performance in terms of scope and sensitivity is presented. Overall,
      the platform encompasses one stream for the determination of 105 compounds in a
      run (based on acidic QuEChERS-like), plus two streams for 23 beta-lactams
      (alkaline QuEChERS-like) and 10 tetracyclines (low-temperature partitioning),
      respectively, and a dedicated stream for 14 aminoglycosides (molecularly
      imprinted polymer).

PMID- 29324076
TI  - Brain Functional Changes before, during, and after Clinical Pain.
AB  - This study used an emerging brain imaging technique, functional near-infrared
      spectroscopy (fNIRS), to investigate functional brain activation and connectivity
      that modulates sometimes traumatic pain experience in a clinical setting.
      Hemodynamic responses were recorded at bilateral somatosensory (S1) and
      prefrontal cortices (PFCs) from 12 patients with dentin hypersensitivity in a
      dental chair before, during, and after clinical pain. Clinical dental pain was
      triggered with 20 consecutive descending cold stimulations (32 degrees  to 0
      degrees C) to the affected teeth. We used a partial least squares path modeling
      framework to link patients' clinical pain experience with recorded hemodynamic
      responses at sequential stages and baseline resting-state functional connectivity
      (RSFC). Hemodynamic responses at PFC/S1 were sequentially elicited by
      expectation, cold detection, and pain perception at a high-level coefficient
      (coefficients: 0.92, 0.98, and 0.99, P < 0.05). We found that the pain ratings
      were positively affected only at a moderate level of coefficients by such
      sequence of functional activation (coefficient: 0.52, P < 0.05) and the baseline
      PFC-S1 RSFC (coefficient: 0.59, P < 0.05). Furthermore, when the dental pain had
      finally subsided, the PFC increased its functional connection with the affected
      S1 orofacial region contralateral to the pain stimulus and, in contrast,
      decreased with the ipsilateral homuncular S1 regions ( P < 0.05). Our study
      indicated for the first time that patients' clinical pain experience in the
      dental chair can be predicted concomitantly by their baseline functional
      connectivity between S1 and PFC, as well as their sequence of ongoing hemodynamic
      responses. In addition, this linked cascade of events had immediate after-effects
      on the patients' brain connectivity, even when clinical pain had already ceased.
      Our findings offer a better understating of the ongoing impact of affective and
      sensory experience in the brain before, during, and after clinical dental pain.

PMID- 29324077
TI  - Screening of 23 beta-lactams in foodstuffs by LC-MS/MS using an alkaline QuEChERS
      like extraction.
AB  - A fast and robust high performance LC-MS/MS screening method was developed for
      the analysis of beta-lactam antibiotics in foods of animal origin: eggs, raw
      milk, processed dairy ingredients, infant formula, and meat- and fish-based
      products including baby foods. QuEChERS extraction with some adaptations enabled
      23 drugs to be simultaneously monitored. Screening target concentrations were set
      at levels adequate to ensure compliance with current European, Chinese, US and
      Canadian regulations. The method was fully validated according to the European
      Community Reference Laboratories Residues Guidelines using 93 food samples of
      different composition. False-negative and false-positive rates were below 5% for
      all analytes. The method is adequate for use in high-routine laboratories. A 1
      year study was additionally conducted to assess the stability of the 23 analytes
      in the working standard solution.

PMID- 29324078
TI  - What an Evidence-based Guideline for Fatigue Risk Management Means for Us:
      Statements From Stakeholders.

PMID- 29324079
TI  - Shorter Versus Longer Shift Durations to Mitigate Fatigue and Fatigue-Related
      Risks in Emergency Medical Services Personnel and Related Shift Workers: A
      Systematic Review.
AB  - BACKGROUND: This study comprehensively reviewed the literature on the impact of
      shorter versus longer shifts on critical and important outcomes for Emergency
      Medical Services (EMS) personnel and related shift worker groups. METHODS: Six
      databases (e.g., PubMed/MEDLINE) were searched, including one website. This
      search was guided by a research question developed by an expert panel a priori
      and registered with the PROSPERO database of systematic reviews
      (2016:CRD42016040099). The critical outcomes of interest were patient safety and
      personnel safety. The important outcomes of interest were personnel performance,
      acute fatigue, sleep and sleep quality, retention/turnover, long-term health,
      burnout/stress, and cost to system. Screeners worked independently and full-text
      articles were assessed for relevance. Data abstracted from the retained
      literature were categorized as favorable, unfavorable, mixed/inconclusive, or no
      impact toward the shorter shift duration. This research characterized the
      evidence as very low, low, moderate, or high quality according to the Grading of
      Recommendations, Assessment, Development, and Evaluation (GRADE) methodology.
      RESULTS: The searched yielded n = 21,674 records. Of the 480 full-text articles
      reviewed, 100 reported comparisons of outcomes of interest by shift duration. We
      identified 24 different shift duration comparisons, most commonly 8 hours versus
      12 hours. No one study reported findings for all 9 outcomes. Two studies reported
      findings linked to both critical outcomes of patient and personnel safety, 34
      reported findings for one of two critical outcomes, and 64 did not report
      findings for critical outcomes. Fifteen studies were grouped to compare shifts
      <24 hours versus shifts >=24 hours. None of the findings for the critical
      outcomes of patient and personnel safety were categorized as unfavorable toward
      shorter duration shifts (<24 hours). Nine studies were favorable toward shifts
      <24 hours for at least one of the 7 important outcomes, while findings from one
      study were categorized as unfavorable. Evidence quality was low or very low.
      CONCLUSIONS: The quality of existing evidence on the impact of shift duration on
      fatigue and fatigue-related risks is low or very low. Despite these limitations,
      this systematic review suggests that for outcomes considered critical or
      important to EMS personnel, shifts <24 hours in duration are more favorable than
      shifts >=24 hours.

PMID- 29324081
TI  - Determination of endogenous concentrations of nitrites and nitrates in different
      types of cheese in the United States: method development and validation using ion
      chromatography.
AB  - Nitrites and nitrates can be present in dairy products from both endogenous and
      exogenous sources. In the European Union (EU), 150 mg kg-1 of nitrates are
      allowed to be added to the cheese milk during the manufacturing process. The
      CODEX General Standard for Food Additives has a maximum permitted level of 50 mg
      kg-1 residue in cheese, while in the United States (U.S.) nitrates are unapproved
      for use as food additives in cheese. In order to be able to investigate imported
      cheeses for nitrates intentionally added as preservatives and the endogenous
      concentrations of nitrates and nitrites present in cheeses in the U.S.
      marketplace, a method was developed and validated using ion chromatography with
      conductivity detection. A market sampling of cheese samples purchased in the
      Washington DC metro area was performed. In 64 samples of cheese, concentrations
      ranged from below the method detection limit (MDL) to 26 mg kg-1 for nitrates and
      no concentrations of nitrites were found in any of the cheese samples above the
      MDL of 0.1 mg kg-1. A majority of the samples (93%) had concentrations below 10
      mg kg-1, which indicate the presence of endogenous nitrates. The samples with
      concentrations above 10 mg kg-1 were mainly processed cheese spread, which can
      contain additional ingredients often of plant-based origin. These ingredients are
      likely the cause of the elevated nitrate concentrations. The analysis of 12
      additional cheese samples that are liable to the intentional addition of
      nitrates, 9 of which were imported, indicated that in this limited study,
      concentrations of nitrate in the U.S.-produced cheeses did not differ from those
      in imported samples.

PMID- 29324080
TI  - Risk assessment of dietary exposure to perchlorate for the Austrian population.
AB  - Perchlorate is frequently found as contaminant in a variety of food. Based on
      analytical data of perchlorate occurrence in food products from the Austrian
      market, this study calculated dietary perchlorate exposure of the Austrian
      population for the three age classes of adults, children and infants.
      Furthermore, a detailed risk assessment was conducted based on the tolerable
      daily intake (TDI) of 0.3 ug/kg body weight/day, established by the European Food
      Safety Authority in 2014. Calculations of a scenario of average food consumption
      did not indicate elevated health risks by dietary perchlorate uptake. Exposure
      estimates reached only 12%, 26% and 24% of the TDI for adults, children and
      infants, respectively. However, in a scenario of high consumption, the TDI was
      exceeded by all age classes with 132%, 161% and 156%. The major cause for this
      exceedance is the comparatively high perchlorate contamination of spinach, but
      also other leaf vegetables, legumes and pineapples, leading to elevated exposure
      of high consumers. Our calculations reveal that the current provisional intra
      Union trade reference level for perchlorate in spinach of 0.2 mg/kg, advocated by
      the European Commission, is not sufficient to protect high consumers against
      possible health risks. In order to reduce health risks to a tolerable level for
      all consumers, lowering of the regulatory maximum perchlorate concentrations is
      indicated. Moreover, a generally diversified diet can also counteract excessive
      exposure to perchlorate as well as to other harmful food contaminants.

PMID- 29324082
TI  - Sensory dissociation in chronic low back pain: Two case reports.
AB  - Patients with chronic low back pain often report that they do not perceive their
      painful back accurately. Previous studies confirmed that sensory dissociation
      and/or discrepancy between perceived body image and actual size is one of the
      specific traits of patients with chronic pain. Current approaches for measuring
      sensory dissociation are limited to two-point-discrimination or rely on pain
      drawings not allowing for quantitative analysis. This case study reports the
      sensory dissociation of two cases with chronic low back pain using a recently
      published test (point-to-point-test (PTP)) and a newly developed test (two-point
      estimation (TPE)). Both patients mislocalized tactile stimuli delivered to the
      painful location compared to non-painful locations (PTP test). In addition, both
      patients perceived their painful lumbar region differently from non-painful sites
      above and below and contralateral to the painful site. TPE data showed two
      distinct clinical patterns of sensory dissociation: one patient perceived the two
      point distance in the painful area as expanded, while the other patient perceived
      it as shrunk. The latter pattern of sensory dissociation (i.e., pattern shrunk)
      is likely to respond to sensory training. Whether enlarged patterns of sensory
      dissociation are more resistant to treatment remains unknown but would explain
      the low effectiveness of previous studies using sensory training in chronic low
      back pain populations. Subgrouping patients according to their sensory
      discrimination pattern could contribute to the choice and effectiveness of the
      treatment approach.

PMID- 29324083
TI  - Effects of Napping During Shift Work on Sleepiness and Performance in Emergency
      Medical Services Personnel and Similar Shift Workers: A Systematic Review and
      Meta-Analysis.
AB  - BACKGROUND: Scheduled napping during work shifts may be an effective way to
      mitigate fatigue-related risk. This study aimed to critically review and
      synthesize existing literature on the impact of scheduled naps on fatigue-related
      outcomes for EMS personnel and similar shift worker groups. METHODS: A systematic
      literature review was performed of the impact of a scheduled nap during shift
      work on EMS personnel or similar shift workers. The primary (critical) outcome of
      interest was EMS personnel safety. Secondary (important) outcomes were patient
      safety; personnel performance; acute states of fatigue, alertness, and
      sleepiness; indicators of sleep duration and/or quality; employee
      retention/turnover; indicators of long-term health; and cost to the system. Meta
      analyses were performed to evaluate the impact of napping on a measure of
      personnel performance (the psychomotor vigilance test [PVT]) and measures of
      acute fatigue. RESULTS: Of 4,660 unique records identified, 13 experimental
      studies were determined relevant and summarized. The effect of napping on
      reaction time measured at the end of shift was small and non-significant (SMD
      0.12, 95% CI -0.13 to 0.36; p = 0.34). Napping during work did not change
      reaction time from the beginning to the end of the shift (SMD -0.01, 95% CI -25.0
      to 0.24; p = 0.96). Naps had a moderate, significant effect on sleepiness
      measured at the end of shift (SMD 0.40, 95% CI 0.09 to 0.72; p = 0.01). The
      difference in sleepiness from the start to the end of shift was moderate and
      statistically significant (SMD 0.41, 95% CI 0.09 to 0.72; p = 0.01). CONCLUSIONS:
      Reviewed literature indicated that scheduled naps at work improved performance
      and decreased fatigue in shift workers. Further research is required to identify
      the optimal timing and duration of scheduled naps to maximize the beneficial
      outcomes.

PMID- 29324084
TI  - Protein association of beta-N-methylamino-L-alanine in Triticum aestivum via
      irrigation.
AB  - Bioaccumulation of several cyanotoxins has been observed in numerous food webs.
      More recently, the neurotoxic, non-proteinogenic amino acid beta-N-methylamino-L
      alanine (BMAA) was shown to biomagnify in marine food webs. It was thus necessary
      to assess whether a human exposure risk via a terrestrial food source could
      exist. As shown for other cyanotoxins, spray irrigation of crop plants with
      cyanobacterial bloom-contaminated surface water poses the risk of toxin transfer
      into edible plant parts. Therefore, in the present study, we evaluated a possible
      transfer of BMAA via spray irrigation into the seeds of one of the world's most
      widely cultivated crop plants, Triticum aestivum. Wheat plants were irrigated
      with water containing 10 ug L-1 BMAA until they reached maturity and seed-bearing
      stage (205 days). Several morphological characteristics, such as germination
      rate, number of roots per seedling, length of primary root and cotyledon, and
      diameter of the stems were evaluated to assess the effects of chronic exposure.
      After 205 days, BMAA bioaccumulation was quantified in roots, shoots, and mature
      seeds of T. aestivum. No adverse morphology effects were observed and no free
      intracellular BMAA was detected in any of the exposed plants. However, in mature
      seeds, protein-associated BMAA was detected at 217 +/- 150 ng g FW-1;
      significantly more than in roots and shoots. This result demonstrates the
      unexpected bioaccumulation of a hydrophilic compound and highlights the demand to
      specify in addition to limit values for drinking water, tolerable daily intake
      rates for the cyanobacterial-neurotoxin BMAA.

PMID- 29324085
TI  - Hyperparasitism of an Avian Ectoparasitic Hippoboscid Fly, Ornithomya
      anchineuria, by the Mite, Myialges Cf. Borealis, in Alberta, Canada.
AB  - Hippoboscid flies (Diptera: Hippoboscidae) include species that are ectoparasites
      of birds in the Northern Hemisphere, but little is known regarding their
      taxonomy, parasites, avian host associations, or geographical distribution in
      North America. In late August of 2013 and 2014, we collected hippoboscid flies
      from live birds trapped in mist nets as part of a banding study in Cypress Hills
      Interprovincial Park in southeastern Alberta, Canada. A total of 113 birds
      comprising 9 species was examined in 2013. Of these, 18 individuals were infested
      with 1-3 Ornithomya anchineuria Speiser (n = 22 flies; prevalence = 15.9%). Eight
      of these flies carried 1-8 adult female epidermoptid mites anchored to their
      ventral, posterior abdomens. Each female was associated with clusters of up to 30
      stalked eggs. The first pair of tarsi on adult female mites was highly modified
      as anchors, indicating permanent attachment through the host cuticle.
      Morphological traits identified these mites as Myialges cf. borealis Mironov,
      Skirnisson, Thorarinsdottier and Nielsen. Cytochrome c oxidase subunit 1 ( COX1)
      gene sequences obtained for 2 mites were distinct from those previously reported
      for species of Myialges, being most similar to Myialges trinotoni Cooreman. The
      paucity of available gene sequences for Myialges and related genera of
      epidermoptid mites prevents any further conclusions regarding taxonomy. These
      findings extend previous reports of O. anchineuria from Pacific and Atlantic
      coasts of Canada inland to the central migratory flyway of the Northern Great
      Plains and expand the limited information available for Myialges spp.

PMID- 29324086
TI  - How Robust is the Influence of Causal Explanation on Clinical Judgments?
      Assessments in Structured Clinical Interviews.
AB  - When causal life-event explanations for disorder symptoms are available,
      clinicians tend to explain away those symptoms (Ahn, Novick, & Kim, 2003 ; Meehl,
      1973 ), eschewing formal diagnostic guidelines such as the DSM-5 (American
      Psychiatric Association, 2013 ). We asked whether this effect is attenuated in
      the context of a structured diagnostic clinical interview procedure, which
      deliberately directs evaluators' attention to symptoms alone, or whether it is
      robust enough to continue to emerge. Across two experiments, lay evaluators given
      causal life-event explanations for disordered behaviors gave them lower judgments
      of abnormality and need for treatment compared to evaluators not given such
      explanations, regardless of whether they used a structured clinical interview.
      Thus, causal life-event explanations may have significant impact on clinical
      evaluations regardless of the mode of assessment. Implications for the clinical
      utility of structured interviews and the role of life-event context in diagnosis
      and classification are discussed.

PMID- 29324087
TI  - Spousal age differences and violence against women in Nigeria and Tanzania.
AB  - Much research has been conducted on the extent of violence against women (VAW)
      and the underlying risk factors associated with VAW. Unfortunately, research into
      the implications of spousal age-related factors for VAW remains underexplored.
      This study explored the implications of spousal age gaps for VAW in Tanzania and
      Nigeria. Data from the 2008 Nigeria (n = 33,385) and 2010 Tanzania Demographic
      and Health Surveys (DHS) (n = 10,139) for women aged 15-49 years were used. We
      used univariate and multivariate statistical analyses to assess the relationship
      between VAW and spousal age-related contextual factors. Nearly half (44.00%) of
      Tanzanian participants and 42.48% of Nigerian participants reported having
      experienced VAW. Results from the multiple logistic regression models across the
      two countries showed that a spousal age gap of more than 15 years, region of
      residence, lower age at marriage, and lower educational attainment were
      statistically associated with VAW. The contexts in which women live are
      associated with their experiencing violence. Less educated women and young women
      were more likely to report having experienced partner violence compared to their
      older, more educated counterparts in both countries.

PMID- 29324088
TI  - Validation of a rapid lateral flow method for the detection of cows' milk in
      water buffalo, sheep or goat milk.
AB  - For many years, the adulteration of milk from sheep, goats or water buffalos with
      cows' milk has been a widespread practice due to the higher cost of milk from
      those other species. Because of this, great concern has been shown by many
      Protected Designation of Origin councils that have to assure the quality and
      genuineness of the cheese produced by their associates. Therefore, the whole
      production chain needs analytical tools that allow the control of potential
      adulteration. Rapid methods to be used in the field are scarce and have not been
      validated according to international guidelines. The aim of this work has been to
      validate a rapid test based on lateral flow immunochromatography to detect cows'
      milk in milk from other species, including buffalo's milk, according to AOAC
      guidelines. No false-positive result was found after analysing 146 known negative
      samples from individual animals. The lowest level of adulteration with a
      Probability of Detection (POD) of 1.00 (confidence interval between 0.94 and
      1.00) was found at 0.5% of cows' milk. This level is below the current EU allowed
      level of cows' milk, set at 1%. Variations in the time of assay, volume of the
      analysis buffer and different batches of the test were evaluated to detect any
      effect on the false-positive rate or on the limit of detection of the test. The
      effects of compositional factors (such as high level of fat, protein and somatic
      cell counts) were also evaluated. The new rapid test to detect cows' milk in milk
      from other species is shown to be an adequate tool to control milk quality in
      routine analysis. This kind of test is very easy to use and it can be performed
      by untrained staff during milk collection at the farm or upon arrival at dairies.

PMID- 29324089
TI  - Development and content validation of a questionnaire to assess moral distress
      among social workers in long-term care facilities.
AB  - OBJECTIVE: Despite the significance of ethical issues faced by social workers,
      research on moral distress among social workers has been extremely limited. The
      aim of the current study is to describe the development and content validation of
      a unique questionnaire to measure moral distress among social workers in long
      term care facilities for older adults in Israel. METHODS: The construction of the
      questionnaire was based on a secondary analysis of a qualitative study that
      addressed the moral dilemma of social workers in nursing homes in Israel. A
      content validation included review and evaluation by two experts, a cognitive
      interview with a nursing home social worker, and three focus groups of experts
      and the target population. RESULTS: The initial questionnaire consisted of 25
      items. After the content validation process the questionnaire in its final
      version, consisted of 17 items and included two scales, measuring the frequency
      of morally loaded events and the intensity of distress that followed them.
      CONCLUSIONS: We believe that the questionnaire can contribute by broadening and
      deepening ethics discourse and research, with regard to social workers'
      obligation dilemmas and conflicts.

PMID- 29324090
TI  - Introducing the International Palliative Nursing Network.
AB  - During the Ninth International Cancer Nursing Conference held in Brighton last
      year, an evening symposium was hosted by Alison Ferguson and Jeanette Webber on
      behalf of the Royal College of Nursing Palliative Nursing Group in the United
      Kingdom. The purpose of the meeting was to enable delegates to explore the
      possibility of developing an International Palliative Nursing Network (IPNN).
      Thirty two nurses from fifteen countries attended the symposium and there was a
      strong consensus that the development of the Network was both timely and viable.

PMID- 29324091
TI  - New challenges for palliative nursing.
AB  - Editorials by Jeanette Webber and Libby White (IJPN 2(3)) explored threats to
      both the nursing profession and palliative nursing as the health system faces the
      reality of limited resources and expanding client needs. I wish to pick up on
      these issues in the light of changes proposed for palliative care in one
      Australian state, Victoria. My central argument is that to secure the future of
      palliative nursing, efforts must focus on demonstrating clearly the value and
      contribution of nurses to client and family outcomes. Why do I think we are
      challenged to do this?

PMID- 29324092
TI  - Action research in a palliative care education programme.
AB  - Using an action research approach, the author worked with district nurses to
      enable them to identify their own palliative care education needs and to plan the
      appropriate education programme, with reflective practice enabling the
      identification of further education needs. This approach overcame some of the
      problems of pre-planned, unresponsive palliative care education programmes. Both
      the learning and the action research approach are developed through continual
      reflective practice, which reduces the theory-practice gap as theory is generated
      from practice. The knowledge gained from reflective practice is as relevant to
      nursing as the knowledge derived from academic theories. Reflective practice
      within palliative care education facilitates learning in a relatively new field
      of practice and generates a greater understanding of the complexities of
      palliative care and associated education needs.

PMID- 29324093
TI  - The net is out there.
AB  - This paper seeks to introduce the resources available via the Internet to improve
      information and education provision within palliative care. It describes well
      established online sources and how they may be found, introduces new terms
      related to Internet use and describes some of the equipment required for Internet
      access.

PMID- 29324094
TI  - Quality of life during high dose chemotherapy for breast cancer.
AB  - Asmall sample of women (n=9) receiving high dose chemotherapy for advanced breast
      cancer were asked to complete a quality of life measure (QLQ-C30) at three time
      points: prior to, during and post treatment. Despite the onset of severe side
      effects, no significant deterioration in quality of life was recorded in terms of
      physical, role, emotional, cognitive or social functioning. The role of the
      clinical nurse specialist (CNS) in providing continuity of care as well as
      support and information for these women is discussed. Further work in this area
      with larger sample sizes is needed to confirm these findings and to further
      investigate the role of the CNS in this context.

PMID- 29324095
TI  - Exploring the nature and impact of fatigue in advanced cancer.
AB  - This paper offers an insight into the nature and impact of fatigue through the
      triadic perceptions of patients with advanced cancer, family members or friends,
      and health care professionals involved with their care. Their views were accessed
      through a case study undertaken at a cancer centre and funded by Macmillan Cancer
      Relief. The aim was to identify aspects of the experience that may be amenable to
      future nursing intervention.

PMID- 29324096
TI  - Whom to help? An exploration of the assessment of grief.
AB  - Palliative care, and the nursing care associated with it, includes the time
      around bereavement. Assessment of whether people are at risk of adverse
      bereavement consequences or suffer such consequences during their time of grief
      is important. Such assessment, which palliative care nurses are ideally placed to
      perform, can target those who need more support and intervention. This review
      investigates factors which it is important to recognise during nursing assessment
      of risk and outcome, with particular emphasis on the use of published tools.
      Three main recommendations are made: for provision of education about grief
      assessment for nurses; for more careful choosing and use of assessment tools; and
      for careful consideration of timing of assessment.

PMID- 29324097
TI  - Patient management and docetaxel.
AB  - Potent new drugs such as docetaxel (Taxotere(r)) will alter our perspective on
      advanced breast cancer, allowing significant disease responses and symptom
      palliation in many patients. The toxicities associated with docetaxel are
      generally predictable and manageable and usually reversible. Docetaxel is
      suitable for use in the outpatient setting. This report describes early
      experience with the drug in a nurse-assisted day case chemotherapy clinic at the
      Velindre NHS Trust Hospital and offers practical guidance on the prevention and
      handling of side-effects.

PMID- 29324098
TI  - Dehydration and the dying patient.
AB  - The management of dehydration in the terminally ill is a complex and emotive
      issue. Some health care professionals contend that a reduced fluid intake may
      result in dehydration which is both painful and distressing for the patient.
      Conversely, others suggest that artificial hydration has not been proven to
      benefit dying patients and may even add to their distress both physically and
      psychologically. These benefits and burdens are also of great concern to the
      relatives of dying patients and the health professionals who care for them. This
      paper reviews the literature concerning the pathophysiology of dehydration and
      discusses the effects of dehydration on dying patients.

PMID- 29324099
TI  - Palliative care services and settings: comparing care.
AB  - The focus of this project was to review palliative care literature on services
      and settings to establish whether they meet needs of patients and expectations of
      care providers. In the first part of this two-part article, issues such as the
      actual and preferred location of death, the quality of care given and comparison
      of different care settings providing palliative care are identified. The studies
      were fairly consistent in the information provided regarding care for the
      terminally ill patient. Primarily, hospice and hospice-based home care teams
      emerged as the providers of best care. The literature highlighted the fact that
      dying is a complex process which hinders researchers by making measurement
      difficult; consequently research assessing the effectiveness of palliative care
      has been limited. Since palliative care is multi-dimensional, it cannot be easily
      encompassed by one means of assessment and results gained in one care setting are
      not necessarily applicable to others. Given the variety of services available,
      purchasers, providers and users need to know for which patients hospice is most
      effective and which care models work best. There is therefore a need to design
      and carry out studies which advance the understanding of dying and the care that
      will influence this process.

PMID- 29324100
TI  - New innovative treatment in metastatic colorectal cancer.
AB  - Campto is a useful new agent in the treatment of colorectal cancer that can offer
      good quality palliative care for many metastatic colorectal cancer patients who
      have failed 5-FU. The key to successful treatment with Campto is to prescribe it
      for patients with a good performance status and without bulky disease.

PMID- 29324101
TI  - Beyond Hippocrates: ethics in palliative care.
AB  - Doctors and nurses work together in the care of patients but the practice of
      nursing has a different emphasis from that of medicine. Because of the close
      working relationship, nursing has historically adopted a traditional biomedical
      view to understand practice and assist in decision making. In this article, the
      author argues that the traditional biomedical perspective does not provide a
      framework to explain the unique relationships that develop between nurses and
      their patients. In particular, the wholehearted adoption of bioethics creates a
      foundation for collaboration with doctors but does not allow nurses to articulate
      their unique ethical practice. An argument is presented for the nursing
      discipline to explore the ethic of care as a framework for the ethical analysis
      of clinical nursing practice. Palliative care nurses are well placed to promote
      and research the ethic of care.

PMID- 29324102
TI  - For whenever I am weak, I am strong....
AB  - A large scale empirical study concerning spiritual pain at the end of life was
      set up by a multi-disciplinary group of palliative care specialists in Flanders,
      Belgium. All Flemish speaking palliative care health workers were sent a
      questionnaire concerning spiritual/religious needs, care and growth. This paper
      focuses on issues relating to spiritual needs and growth of the caregivers.
      Although respondents considered the ability to identify personal spiritual needs
      as an important criterion for offering good spiritual care, in-depth analysis
      suggests a considerable gap between theoretical insight and daily practice.
      Findings advocate greater awareness and assertiveness among caregivers regarding
      their own spiritual experiences. A structural implementation of supervision to
      address the hidden spiritual agenda of the palliative team may need to pre-empt
      systems that teach how to respond more adequately to patients' spiritual needs.

PMID- 29324103
TI  - Directions in spirituality: an introduction to the theme.
AB  - When, in 1995, the Editorial Board discussed the subject of spirituality it
      became clear that those of us assembled had very different perceptions of this
      intriguing concept. Spiritual pain, angst, search for meaning, faith, hope,
      humanism and the power of love, all sprang to people's lips. It was abundantly
      clear that, despite the myriad opinions which arose, we were committed to a
      common aim.

PMID- 29324104
TI  - Spirituality, language and depth of reality.
AB  - This paper explores the potential for patients to express spiritual concerns
      other than through a religious vocabulary. The spiritual is presented as an
      indivisible dimension rather than a compartment of existence and spiritual
      expressions are regarded as intertwined with autobiography, and attempts to
      discover ultimate meaning in life's events. It is argued that metaphor and symbol
      may reveal truths as compelling as those disclosed by the natural sciences and
      that multiple layers of meaning exist in all human activity and expression.
      Professionals are invited to reflect upon the authenticity of their communication
      with patients, for the simplest act of care may be deeply significant when a
      patient feels that their own sense of reality has been recognised.

PMID- 29324105
TI  - Caring for dying Buddhists.
AB  - This paper provides information on how to offer help and support to Buddhists who
      are seriously ill or dying at home, in hospitals, hospices or nursing homes. It
      begins with an outline of Buddhism, indicating its main teachings and practices.
      This provides the background for a number of practical suggestions that will help
      non-Buddhist carers to understand and, where possible, to meet the spiritual
      needs of their Buddhist patients as death approaches. In the final part of the
      paper, the work of The Buddhist Hospice Trust is outlined.

PMID- 29324106
TI  - The nurse's role in assessing and responding to patients' spiritual needs.
AB  - The spiritual dimension of health care is becoming increasingly prominent,
      particularly in terminal care. It is not always clear, however, what spiritual
      needs are or who has responsibility for spiritual care. The first part of this
      paper takes the form of a literature review which examines the spiritual
      dimension and spiritual need. Spiritual needs, which may be particularly acute
      during terminal illness, are considered broader than religious needs and include
      the need for meaning, purpose, fulfilment, hope/will to live, and belief and
      faith in self, others and God. The role of the nurse in assessing and responding
      to patients' spiritual needs is addressed in the second part of the paper, with
      specific reference to the author's doctoral study. There is indication from this
      study that certain factors related to the patient, nurse, environment and other
      professionals may hinder the fulfilment of patients' spiritual needs. By
      addressing these factors it may be possible to improve spiritual care and
      therefore the quality of dying patients' remaining days.

PMID- 29324107
TI  - Organisational structures and personal spiritual belief.
AB  - This paper is based on the author's experience of working with NHS chaplains who
      may or may not have worked in palliative care areas. 'A Framework for Spiritual,
      Faith and Related Pastoral Care' (1995), developed in response to 'The Patient's
      Charter' (Department of Health (DoH) 1991) provides much of the material that
      underpins this paper. While certain material within this paper relates directly
      to palliative care, the main thrust concerns the principles that sustain good
      organisational practice when trying to meet the increasingly diverse spiritual
      needs of patients. The Framework paper on which this is based recognises the
      major changes that have occurred in the nature of care delivery and, therefore,
      the way in which traditional approaches to chaplaincy have been modified. This
      paper outlines a number of strategies that can be pursued to facilitate this
      change and concludes with some specific observations about the significance of
      change for the palliative care arena.

PMID- 29324108
TI  - The meaning of hope to palliative care cancer patients.
AB  - This paper describes a phenomenological study which sought to explore the meaning
      of hope to patients with cancer who are receiving palliative care. A purposive
      sample of four patients was interviewed using a semi-structured format. Content
      analysis of the themes arising from the transcripts identified three specific
      areas of meaning as influential in maintaining hope; the maintenance of the
      disease as it existed at the time of interview for the individual, underpinned by
      a hope for cure; the existence and presence of significant family members, and an
      anticipated future with them; the maintenance of a positive interest in the
      individual by health care professionals. All participants identified that loss of
      control over any of the hope maintaining factors, would cause loss of hope.
      Within each description of hope were individual meanings. However, the generic
      themes described the essence of the phenomenon of hope. The study thus identified
      the existence of hope, its nature and meaning, for those who participated and is
      a starting point for further research in this area.

PMID- 29324110
TI  - Multi-faith hospices.
AB  - The United Kingdom (UK) today has developed into a multi-cul-tural society.
      Health care professionals are called upon to care for people from cultures that
      are often different from their own. In order to do this effectively there has to
      be understanding and sensitivity to the needs of these patients. Evidence
      suggests that health care professionals are not alert to these needs. Hospices,
      in particular, need to develop an awareness and a sensitivity to other cultures
      in order to care for the service users in a truly holistic sense. The changes
      required in attitude, practice and environment take time, planning and commitment
      from all members of the multi-disciplinary team, and indeed from the whole
      organisation.

PMID- 29324111
TI  - Spiritual care: the heart of palliative nursing.
AB  - The spiritual realm can be broadly defined as the life force springing from the
      unknown that pervades each person's entire being. It encompasses the volitional,
      emotional, ethical, social, intellectual and physical dimensions. It is the
      centre or core that integrates the whole person, surpassing the biological and
      the psychosocial. It is the self, or I, the essence of person-hood, the God
      within, that which communicates with the transcendent. It is that part of each
      individual that aspires to ultimate awareness, meaning, value, purpose, beauty,
      dignity, relatedness and integrity. The spiritual is the source of faith, hope
      and courage. It inspires theology, artistic inspiration and expression, love and
      healing.

PMID- 29324112
TI  - Signposts on the journey: the place of ritual in spiritual care.
AB  - An exploration of the nature and function of rituals is undertaken in this paper
      to consider the importance and relevance of rituals in spiritual care, within the
      palliative care speciality. Understandings of ritual tend to focus on either
      their association with religious practices or ritualistic action. However,
      rituals can still provide a practical and symbolic way to facilitate change for
      individuals, both within an organisational context and in spiritual journeys
      within their own lives. Empirical work examining the hospice culture, using a
      rites of passage framework, illustrates how the presence of rituals within
      hospice care may be helpful for individuals experiencing the transition from life
      to death.

PMID- 29324113
TI  - An exploration of the concept of spirituality.
AB  - This paper explores the concept of spirituality using the framework developed by
      Walker and Avant (1995). Consideration of the concept, as used within nursing,
      suggested two broad categories: one relating to religious connotations and the
      second relating to non-religious connotations such as belief in the
      source/principle of life the characteristics or attributes of a person. Use of
      the concept analysis framework proved to be limited, because of the subjective
      and often intangible nature of spirituality. It remains a personal and
      individualistic concept which frustrates the development of a simple, standard
      definition. It may therefore be more appropriate for future nursing research and
      practice to explore nursing practices such as interpersonal interaction and
      communication. This may then facilitate nurses' assessment and exploration of
      spirituality with their patients.

PMID- 29324114
TI  - Teaching spiritual care to nurses: an alternative approach.
AB  - This paper presents an approach to teaching spiritual care that is underpinned by
      a traditional philosophy of care as agape. In this approach spiritual care is
      considered a fundamental character of care, not a self-conscious addition. The
      caring function of the nurse is qualitatively differentiated from that of the
      religious minister, whose role is considered to be currently underestimated. From
      this perspective, teaching spiritual care to nurses is not so much achieved
      through theoretical or experiential analysis and reflection, but by following an
      established moral pattern; it is not taught so much as caught. It is argued that
      this traditional approach to spiritual care provides an alternative to current
      educational ideologies in nursing, and reflects patients' and nurses' own
      attitudes to - and expectations of - the spiritual dimension of care.

PMID- 29324115
TI  - The experiences and needs of patients attending a cancer support group.
AB  - This paper explores the experiences of people who, following a diagnosis of
      cancer, initially received treatment in a conventional hospital setting under the
      direction of professional health-care workers and then joined a cancer support
      group. In this study it is assumed that an increased awareness of the experiences
      and needs of patients with a malignant disease will enhance the ability of
      professional health-care workers to provide more effective care and to meet the
      physical, psychological, social and spiritual needs of cancer patients. A
      phenomenological approach was employed in an attempt to understand the
      experiences from the perspective of the respondents in the study.

PMID- 29324116
TI  - Staff support in hospices.
AB  - This article reports on a descriptive study of staff support in 116 hospices in
      the UK. The study took the form of a postal questionnaire survey. Before the
      survey an extensive review of the literature was carried out which highlighted
      the causes and effects of stress, both generally and in palliative care, along
      with coping strategies. The literature emphasised the intense nature of
      palliative care and the importance of having effective support mechanisms in
      place for staff (McKee, 1995). The results of this survey showed that, in
      general, hospices are attempting to deal with staff stress by offering group
      and/or individual support.

PMID- 29324117
TI  - Clinical supervision in sustaining and developing nursing practice.
AB  - Clinical supervision and its influence on practice is of profound importance to
      nursing, midwifery and health visiting. This paper examines the role of clinical
      supervision in context and provides a case study illustration of fundamental
      concepts. A psychodynamic perspective is assumed for the discussion. The case for
      clinical supervision as a means to ensure the safe and effective delivery of
      health care is presented.

PMID- 29324118
TI  - Palliative care in motor neurone disease.
AB  - Motor neurone disease (MND) is a fatal, progressive, neurodegenerative disease
      with no known cure. Deterioration of upper and lower motor neurones leads to
      progressive weakness, and disability and death usually occur within 5 years. The
      symptoms of MND are many and varied, and lead to progressive loss of function and
      potential loss of dignity. Professionals may wrongly give the impression that
      little can be done for patients with this devastating disease. However, symptom
      relief is of paramount importance in maintaining quality of life in MND. Patients
      may suffer from pain and immobility, speech and swallowing problems, emotional
      difficulties, bowel and bladder problems, dyspnoea and ventilatory failure.
      Nurses and therapists involved in palliative care will have met many of these
      symptoms in other diseases and are well placed to extend their expertise to
      patients with MND and their families.

PMID- 29324119
TI  - Body image: using women who have had breast surgery as a case study.
AB  - This paper attempts to bring together some of the social and historical
      influences which impact on body meaning and thereby influence body image
      formation. Using women with breast cancer as a case study, it is argued that the
      resultant body image construct has implications for women's attitudes towards
      their bodies in general and their breasts in particular. These influences are
      considered in relation to women's response to threats against body image
      integrity such as those posed by surgical intervention for breast cancer.
      Knowledge and awareness of the factors which affect body meaning and body image
      can be used to improve our understanding and care of a wide range of patients
      with advanced disease.

PMID- 29324120
TI  - Nurses are expanding their roles despite widespread demoralisation.
AB  - Throughout the world nurses are under pressure. Changes in approaches to health
      care delivery are occurring in m any countries, resulting in a reduction in human
      and financial resources, downsizing of nursing staff and the increased use of
      unregistered health-care personnel. In the UK, the impact on morale has been
      profound. A recent survey by the Department of Health (1995) has revealed that
      one in three nurses who trained in 1991 and before have now left the profession.
      Of those questioned, 43% stated that they would never consider returning to the
      NHS because of their dissatisfaction with nursing.

PMID- 29324121
TI  - The role of Macmillan nurse tutors: an interview study with post-holders.
AB  - This article explores the role of Macmillan nurse tutors through in-depth, semi
      structured tape-recorded interviews with 22 post-holders, focusing on their
      responsibilities, institutional affiliations and career aspirations. After full
      transcription, these qualitative data were subjected to open coding. Many
      tensions and variations within the role were revealed. However, these tutors
      appeared to be extremely committed to cancer and palliative care. They were
      concerned about how their future educational position would be maintained in a
      changing system of health care and health provision.

PMID- 29324122
TI  - Professional support within hospices.
AB  - During a prospective study in two hospices, 41 nurses were interviewed about
      recent critical incidents at work. Questionnaires based on the work of House
      (1985) were used to measure their perceptions of professional support. At each
      interview, nurses detailed an average of four recent occasions when work-related
      support had been received. Overall, nurses were fairly satisfied with the
      professional support they had received, and it was evident that their direct
      supervisor was the most significant figure. However, some interesting
      distinctions were identified. For example, practical (as opposed to emotional)
      support was the most appreciated, and large meetings were frequently viewed as
      unhelpful. Nurses' friends and relatives were unlikely to be able to meet any
      needs for professional support that were not met in the work setting. The study
      demonstrated how helpful and unhelpful management strategies can be identified
      and how an overall picture of the level of professional support can be
      constructed.

PMID- 29324123
TI  - A teacher's return to clinical nursing practice.
AB  - Having been employed as a nurse educationalist for many years, a return to
      clinical nursing care, while having been a big personal ambition, only became a
      reality in 1992.

PMID- 29324124
TI  - Island Hospice Service - Harare.
AB  - Since 1979, Island Hospice Service (IHS) has provided care for patients with a
      life-threatening illness together with their families and the bereaved. This
      article describes the experiences of a volunteer social worker who was a member
      of the IHS team for 3 years. IHS offers not only a nursing service but also a
      bereavement service, and these are free of charge. Group work includes members
      with a wide age range. There is a support and training network for all staff
      members, including volunteers.

PMID- 29324125
TI  - Correspondence.
AB  - Dear Editor, I am a founding member of the Canadian Palliative Care Association.
      I helped my parents (in Canada) and my grandmother (in Holland) live at home
      until they died. I am a writer and educator and have written 16 books, including
      three in the field of hospice/palliative care. I write palliative care books from
      the perspective of the family and the patient. I am, at present, working on a
      fourth palliative care book Successful Hospice Care.

PMID- 29324126
TI  - Group cognitive behavioural therapy: an intervention for cancer patients.
AB  - There is considerable evidence to suggest that cancer patients, including those
      with advanced disease, experience significant and long-term psychosocial
      problems. Work using group cognitive behavioural therapy with cancer patients has
      recently demonstrated a way in which it may be possible to treat emotionally
      distressed individuals effectively. This article reviews the literature on group
      cognitive behavioural psychotherapy and discusses for practitioners of all
      disciplines the important techniques, the value of time-limited interventions,
      the type of patients who may benefit, and where and how to facilitate successful
      interventions. Health workers with an interest in the emotional care of patients
      are thus provided with some understanding of the value that group cognitive
      behavioural psychotherapy may hold for them.

PMID- 29324127
TI  - A different kind of care.
AB  - This article describes an interim home for terminally ill patients who, despite
      an extended prognosis, do not require highly skilled care. Patients are assessed
      for suitability by a professional nurse from the interim home. The assessment,
      although not rigid, is quite specific. Care is provided by community care workers
      under the supervision of, and backup from, a professional nurse. The article
      includes issues of family involvement, the mode of dying and a study of staff
      stress levels. Comparisons are drawn between the interim home and the high care
      hospice centre and some interesting findings emerge.

PMID- 29324128
TI  - Demonstrating the value of palliative care.
AB  - Recently, three issues have been covered in the UK nursing press which have
      highlighted some of the conflicting perspectives confronting nurses today. The
      first has arisen out of work established in 1995 when an Expert Advisory Group
      was set up by the Chief Medical Officers of England and Wales to advise on the
      organization of cancer services. Following wide consultation, the report was
      launched and is now being implemented (Department of Health, 1995). The framework
      identifies three contexts in which cancer treatment and care will be delivered -
      the cancer centre, the cancer unit and the primary care setting - and makes a
      strong case for the establishment of key specialist nursing posts in each of
      these settings.

PMID- 29324129
TI  - It never rained in the house of sleep....
AB  - Night - bat black, brooding, all encompassing darkness, blanketing the colours of
      the day; the outlines blur and shapes become fluid.

PMID- 29324132
TI  - Teenagers and loss.
AB  - The teenage years are a difficult phase of life when many physical and emotional
      changes occur. Although the needs of this age group differ from those of children
      and adults, professionals in the hospital setting have been slow to recognize and
      accommodate problems which are specific to teenagers, particularly at times of
      illness or bereavement. This article offers some thoughts on how to help
      teenagers cope with loss, whether it be their own death or the death of a loved
      one.

PMID- 29324131
TI  - Is there a place for euthanasia in palliative care?
AB  - In the current debate about the legalization of euthanasia the' distinction
      between giving care and bringing about death is blurred. Alongside this there is
      an apparent increased commitment to the further development of palliative care.
      Difficulties arise in palliative care when euthanasia is discussed as there is an
      inference that a request for euthanasia results from a failure on the part of the
      carers. Palliative care aims to relieve distress and suffering, but problems
      arise from unrealistic expectations of what can actually be achieved. There is a
      need for professionals to emphasize what is possible in relation to palliative
      care, to acknowledge that there are limitations, and to set realistic and
      carefully identified goals which are more likely to be achieved than impossible
      expectations which could induce individuals to consider euthanasia when
      impossible expectations are not reached. Euthanasia has an impact on the
      relationships between health-care professionals and their patients which give
      rise to a potential alteration of the traditional role.

PMID- 29324133
TI  - Direct access by GPs to palliative nursing.
AB  - This article presents the results of a pilot study evaluating direct access by
      GPs to specialist community palliative nursing support without an intermediary
      visit from a medical consultant. GPs wishing to refer terminally ill patients to
      the community palliative care team were given access via either medical
      assessment or nursing assessment. Results showed that the overall referral rate
      to the service increased during the period of the study. In addition, the new
      service was well received by the GPs who used it. A large number of referrals
      (75%) requested support for the patient and family. This study contributes to the
      ongoing debate about the need to identify and define supportive interventions and
      the most appropriate providers of these.

PMID- 29324134
TI  - Facilitation: the concepts in use in palliative care nursing.
AB  - Facilitation is a fairly common technique for helping palliative care patients in
      the clinical setting. Reflective practice provides an opportunity for
      practitioners to think out the concepts in use while facilitating care. This
      study reports on the views of practitioners who experienced reflective learning
      and facilitation as part of a Course, and attempted to identify, in their
      practice, the concepts they used to facilitate patient care. The aim was to
      recognize concepts that practitioners (and teachers) can use to facilitate care.
      The methods used for research were participant observation and interviews. Data
      analysis consisted of coding and categorizing the concepts emerging from this
      study. The result was identification of the PACTS mnemonic crystallising the key
      concepts in facilitation: Purpose, Action, Collaboration, critical Thinking, and
      Support and confrontation.

PMID- 29324135
TI  - Palliative nursing in a changing health-care system.
AB  - Although palliative care has been practised since ancient times, its development
      as a recognized discipline within health care began some 30 years ago. The
      resulting benefits to patients, including enhanced relief of distressing symptoms
      and improvement in overall quality of life are best demonstrated in the care of
      people with advanced cancer. Continued growth of palliative care, particularly in
      Western countries, has been assured by the emergence of doctors and nurses
      trained in the specialty, who have become the cornerstone of interdisciplinary
      palliative care teams.

PMID- 29324136
TI  - Patient compliance with medication regimen after discharge from palliative care.
AB  - Patient compliance with prescribed medication has been well researched and there
      is a consensus in the literature that noncompliance exists on a large scale. In
      the studies reviewed the level of non-compliance ranged from 38.5% to 60%, but
      very little of this research related specifically to palliative care patients.
      The present study was undertaken to ascertain the level of compliance in a group
      of patients who had been discharged home from a palliative care centre, and to
      obtain their views on taking their medication in order to identify ways in which
      services could be improved.

PMID- 29324137
TI  - The organization and delivery of palliative care services in India.
AB  - A study/lecture tour of India was undertaken by the authors during October and
      November 1995. The purpose of the visit was to provide a programme of education
      in palliative care and to gain a deeper understanding of the care of dying people
      in India. Seven centres were visited and the distance covered was approximately
      4500 km. This article describes existing palliative care links between India and
      the UK and discusses the organization and delivery of palliative care services in
      the areas visited. Problems such as difficulty in accessing services and
      resources are explored. Psychosocial issues relating to peoples' attitudes
      towards illness and uptake of services are also investigated. Some strategies are
      suggested to support the continued development of palliative care in India This
      journey was an opportunity to gain an empathetic understanding of the spiritual,
      psychological, emotional and multicultural palliative care needs of the Asian
      population.

PMID- 29324138
TI  - What terminally ill patients value in the support provided by GPs, district and
      Macmillan nurses.
AB  - The aim of this project was to investigate how patients view the care and support
      provided by their doctors and nurses. Forty-three patients with a life expectancy
      of 1 year or less who were being looked after in their own homes were asked to
      give their views of the support given by general practitioners, district nurses
      and Macmillan nurses. Patients had predominantly positive views of the support
      received. The content of their positive statements suggested that psychosocial
      aspects of support, including communication and kindness and consideration shown,
      were valued most. Actions in the form of helpfulness, organization of support and
      being accessible were also important, while clinical aspects received less
      emphasis. Clinical aspects of care were emphasized more when patients expressed
      negative views of support. Patients' statements suggested that emotional support
      and information were provided predominantly by Macmillan nurses.

PMID- 29324139
TI  - Palliative nursing in New Zealand.
AB  - New Zealand has a well-developed framework for training and supporting palliative
      nurses. Palliative nursing in New Zealand was built on the pioneering efforts of
      nurses working with others in the setting up of hospices and cancer care services
      in the 1970s. The wisdom of established community and religious nursing services,
      and those travellers amongst us who return with new ideas, also contributed.

PMID- 29324140
TI  - A composite model of palliative care for the UK.
AB  - This paper argues that there has been a paradigm shift in recent times in the
      service needs for palliative care as a result of the UK's National Health Service
      internal market structure, the shift to community care and the rising needs of
      the private sector. Nursing models associated with palliative care are reviewed
      and represented within the 'Composite Model of Palliative Care' which blends
      current and traditional models of care, focusing upon a multidisciplinary
      approach involving professionals, family and friends. The roles of advocate,
      manager, educator, carer/therapist, researcher and communicator/counsellor are
      presented as the vehicle to implement the model of care through a learning
      contract and associated clinical supervision. The paper also argues that there is
      a need for specialist palliative care courses at least at diploma level, with
      appropriate professional recognition, designed to make the paradigm shift and to
      project this into clinical practice through a tripartite learning contract
      involving specialist tutor, clinical supervisor and student. The rationale and
      outline of the course are presented along with the argument that this paradigm
      shift needs to take place if palliative care is to be truly holistic care.

PMID- 29324141
TI  - Problem and management of noisy rattling breathing in dying patients.
AB  - Noisy rattling breathing in dying patients is a symptom control problem which has
      attracted only a fleeting mention within the literature. This study investigated
      palliative care nurses' feelings about the problem and the management of noisy
      rattling breathing in dying patients. The aspects studied were based on the
      literature and multidis-ciplinary team discussion, and included nurses' feelings
      about the distress caused by noisy rattling breathing, their perceived confidence
      in providing related nursing care and their thoughts and feelings about the
      established care options. Data were gathered from a convenience sample of twenty
      three palliative care nurses by means of a questionnaire. This data was analysed
      using descriptive statistics. The results revealed that nurses perceived
      relatives to be particularly distressed by noisy rattling breathing, Several
      nurses felt that they lacked confidence in providing related nursing care and
      there was a felt need for clinical guidelines. The limitations of the study are
      discussed and the conclusion highlights the need for further research into this
      symptom control problem.

PMID- 29324142
TI  - Audit of pain and sleep during sleeping hours.
AB  - This joint audit between nursing and medical staff examines the quality of sleep
      experienced during the night and the degree to which pain is controlled in a
      specialist palliative care unit. Patients and nurses independently completed
      short questionnaires incorporating categorical rating scales for pain and sleep.
      Patients' perceptions were directly sought. Nurses were good at assessing whether
      patients slept well and also whether they were pain free. However assessment was
      less accurate in judging the degree of pain when present or quality of sleep when
      poor. Areas to improve pain control and sleep were identified. This audit
      methodology has the potential to provide outcome measures of quality of
      palliative care not only for the individual palliative care provider but also
      wider purchaser and provider bodies.

PMID- 29324143
TI  - Clinical supervision in moderating organisational conflict and preserving
      effective working relationships.
AB  - This paper examines the role of clinical supervision in relation to the work of a
      palliative care nurse, although the issues discussed relate to all nurses
      whatever specialities. The effects of market forces and organisational culture on
      the delivery of human service are explored in context. The writer draws on
      psychoanalytical ego defence construction and existential-phenomenological ideas
      to throw light on the deliberation. Through a case study illustration the writer
      makes a case for the development of a safe and effective working relationships
      helped by clinical supervision and through agreed working arrangements. The
      discussion concludes with the central recommendation that constructing a safe
      working environment for clinical supervision, through which to explore the
      dynamic forces influencing the organisation of health care, transcends
      methodological considerations. (The writer has changed all names and
      circumstances).

PMID- 29324144
TI  - The role and need of the children's hospice in the United Kingdom.
AB  - Despite the growth of the children's hospice movement the public and many health
      professionals do not appear to understand its true role. It provides relief and
      terminal care with practical and emotional support for children with life
      limiting and life-threatening conditions, and their families. It should, however,
      not be seen as the only option open to these families. It is not a substitute for
      good hospital or community care. Paediatric palliative care is a very specialised
      area which requires expert and individualised care. Children's hospices could be
      seen as local centres of clinical research, education and audit rather than just
      a provision of care.

PMID- 29324145
TI  - Pathophysiology and management of dyspnoea in palliative care and the evolving
      role of the nurse.
AB  - Dyspnoea is a symptom commonly encountered in palliative care, especially with
      patients suffering from advanced cancer. An understanding of the
      pathophysiological mechanisms that are understood to be associated with this
      symptom will enable health professionals to provide more appropriate management
      interventions. A review of the literature was undertaken to explore current
      knowledge on the causes and management of dyspnoea. This paper will describe the
      results of this review by giving an overview of the pathophysiology of dyspnoea,
      and discussing controversial treatment issues. Methods of assessment and the role
      of the nurse in managing this distressing symptom are also explored.

PMID- 29324146
TI  - Palliative nurses' perceptions of the nature and effects of their work.
AB  - This paper presents some of the qualitative findings from a recent research
      project, which explored the nature and effects of palliative nursing care for
      nurses, in New South Wales, Australia. By using story telling as the research
      methodology the participants related their experiences about palliative care
      nursing practice in which they felt they did or did not make a difference to the
      people in their care. The results of this project clearly demonstrated that the
      nature of palliative nursing is expressed by nurses dealing with death, making
      connections, making contracts, demonstrating advocacy, building interpersonal
      relationships, requiring family and colleague support and involvement in issues.
      The effects of palliative nursing were described as whether nurses were able to
      find solutions; facilitate breakthroughs, acceptance and support; reflect of
      their values and feelings.

PMID- 29324147
TI  - Stabilisation in colorectal cancer.
AB  - Stabilisation of disease (as well as objective response) is an important outcome
      in the treatment of cancer. To test the hypothesis that chemotherapy brings
      positive Quality of Life (QoL) benefits when disease stabilisation is achieved, a
      utility study involving 30 UK nurses experienced in oncology care has been
      carried out. Acting as proxies for cancer patients, the nurses were asked to
      assess the values of various health states associated with the treatment of
      metastatic colorectal cancer. The nurses rated the QoL benefits of stabilisation
      almost as highly as those of partial response (Utility score of 0.95 vs. 1). Side
      effects associated with chemotherapy, however, mean that active management of
      toxicity is needed to preserve QoL benefits. More than 50% of metastatic
      colorectal cancer patients have a partial response or have their disease
      stabilised with the new topoisomerase I inhibitor (irinotecan, CAMPTO(r)). It is
      indicated for use when treatment with 5-fluorouracil (5-FU) has failed. Major
      side-effects are short-lived compared with treatment benefits, so it appears
      that, for patients who respond or who are stabilised, the QoL improvements will
      outweigh any short-term costs of toxicity.

PMID- 29324148
TI  - Euthanasia: failure or autonomy?
AB  - When faced with a request for euthanasia, carers should not immediately assume
      that this has been generated by a failure of care. It is possible to distinguish
      between those patients who can be helped to want to live again and those who
      cannot. Within the second group there will be individuals who choose euthanasia
      not because of psychological problems but because they consider it a rational
      choice, given who they are and how they have lived their lives. In dealing with
      such patients, carers must respect their decision, even when they are unable or
      unwilling to accede to it. Such respect is only possible in a context where
      people feel free to discuss and explore the possibility of euthanasia. If the
      institutional philosophy prevents this, a harm is done to those who believe that
      there is nothing wrong with euthanasia in principle, and that, in fact, it is
      right for them in practice.

PMID- 29324149
TI  - Palliative care and the ethics of resource allocation.
AB  - Resources for health care are scarce, and dividing them fairly is both necessary
      and difficult. Palliative care has a claim on these resources because it is
      concerned with improving the quality of life of those who are dying. However,
      some standard ways of allocating resources, such as the use of Quality Adjusted
      Life Years (QALYs), do not favour the funding of palliative care. Even if this
      can be corrected, there are still problems of allocation within palliative care
      itself: a choice has to be made between funding a complete provision of care for
      some but not others, or using resources to provide a more basic service for all
      those who are in need.

PMID- 29324151
TI  - Care, autonomy and nurse education.
AB  - Paternalism in medicine is giving way to consumerism. When doctors sneeze, nurses
      catch cold. Consumerism is having an equal affect on nursing. For example,
      patient autonomy is currently in vogue. A greater emphasis on the needs and
      wishes of patients is a much needed correction to the times when medical and
      nursing staff rode roughshod over those in their care. However, the danger is
      that we go too far and undermine the personal and professional integrity of
      nurses.

PMID- 29324152
TI  - Palliative care nursing in a curative environment: an Australian perspective.
AB  - This article describes the experiences of two nurses who developed palliative
      care specialty practices in acute general hospitals. The principal goal of, their
      work was to facilitate a smooth curative-palliative transition for patients,
      their families and the hospital staff. A major challenge was finding techniques
      to promote the palliative care philosophy in a curative environment. Staff in
      acute hospitals often work in a paradoxical situation between the ideologies of
      curative and palliative care. This situation would not occur in a hospice or
      palliative care unit. Many nurses apparently assume that palliative care is
      synonymous with terminal care and is therefore only needed when the patient is
      near to death. Palliative care is often perceived by acute hospital staff to be a
      separate entity rather than integral to the common goals for good patient care.
      The first part of this article describes the experiences of a palliative care
      clinical nurse working with staff and patients in a private hospital. The second
      part discusses a clinical lecturer post which was established as a joint
      appointment between a university and a major public hospital in Brisbane,
      Australia. The goal of the joint appointment was to enhance the blending of
      theory and practice and to gain deeper understanding about the experience of
      patients who are dealing with life-threatening disease.

PMID- 29324153
TI  - Ethical issues in multicentre collaborative research on breathlessness in lung
      cancer.
AB  - This article describes, the ethical issues involved in developing a multicentre
      collaborative research project to evaluate a nurse-led clinic for breathlessness
      in patients with lung cancer. In this randomized controlled study, the framework
      of relationships between coordinating researchers and researchers in the
      collaborating centres, and between researchers in the collaborating centres and
      research participants, is identified as the focus of ethical attention. The
      principles of new paradigm and action research are identified as providing a
      basis for ethical research which focuses on the quality of the interaction
      between researcher and participant, and some parallels between this project and
      new paradigm research are explored.

PMID- 29324154
TI  - Helping children to grieve.
AB  - The aim of this article is to address the needs of grieving children, who are
      often excluded from the grieving process. Many adults erroneously believe that
      children do not grieve or that their grief is milder and of a shorter duration
      than that of adults. The first section of the article examines the literature
      dealing with the problems of grieving children. Loss of someone close to a child
      can cause great distress and may have an adverse effect on development.
      Repression or denial of grief in childhood may lead to psychiatric illness in
      adulthood. It is therefore vitally important that adults understand children's
      grief and have some idea of how they can help them through the grieving process.
      The second part of the article draws on the published literature to present a
      number of strategies which may be of benefit in helping children through the
      grieving process.

PMID- 29324155
TI  - Dignity and integrity at the end of life.
AB  - This article briefly examines what is meant by a 'good death' and looks in detail
      at the idea of 'death with dignity' as one such concept. This may be best
      understood not as a manner of dying, but as a manner of treating those who are
      dying. The relationships between dignity, self-respect and integrity are explored
      and illustrated with examples from both the literature and clinical practice.
      Nursing in a way that preserves or restores a patients' dignity in the face of
      illness and death makes severe demands on a nurse's integrity. The importance of
      having institutional mechanisms in place which assist the nurse in this work is
      emphasized, as is the need for clinical supervision in nursing.

PMID- 29324156
TI  - Ethical dimensions in palliative nursing.
AB  - Judging by the content and focus of national and international journals and
      conference programmes, it would appear that the preoccupation of health
      professionals with ethical aspects of care has increased dramatically in recent
      years. Nurses in particular are expressing deep concerns about the ethical
      dimensions of their work and many are opting to undertake advanced educational
      programmes dealing with this subject. It is interesting to reflect on the reasons
      for this growing concern. After all, many of the situations which we face today
      and which give rise to ethical dilemmas have been with us for many years. Life
      support machines, clinical trials and the desire of some to end their lives, when
      continued existence seems meaningless or intolerable, are not situations unique
      to the 1980s or 1990s - indeed, even I can remember them being around when I was
      a student nurse and that is going back some years!

PMID- 29324157
TI  - Orem's self-care model and clinical supervision.
AB  - This article explores Orem's self-care model in relation to the care of a dying
      person and his/her family and gives an overview of the model together with
      illustrations of key concepts. The main recommendation of the article is that
      Orem's model should be viewed within the context of existential humanism. It
      concludes with the view that the model should be linked to the concept of
      clinical supervision.

PMID- 29324158
TI  - Hospital nurses' bereavement support for relatives: study report.
AB  - Health carers in the field of palliative care have developed skills in dealing
      not only with dying people but also with their relatives. The same, however,
      cannot be said for carers in other clinical areas. How do nursing staff in these
      other areas feel about the way they respond to the needs of relatives of the dead
      and dying? Do they feel adequately prepared? This article examines the issue of
      bereavement support provided by nurses to relatives in hospital. It is based on
      semi-structured interviews with 50 nurses in one large teaching hospital. It was
      found that bereavement support varied from ward to ward, and that there was a
      need for greater preparation of nursing staff to take account of the needs of
      relatives. These needs range from practical information to emotional support.
      More educational opportunities should be provided for nurses, and joint workshops
      for medical and nursing staff should be established to explore the issues and
      develop a sensitive approach to relatives in all clinical areas.

PMID- 29324159
TI  - AIDS and community nursing care.
AB  - This article reports on a study commissioned by the Department of Health to
      examine community nursing services for people with HIV disease. Data were
      gathered on discharge, referral patterns and coordination of services for people
      with HIV disease in six health authorities in England. Methods included discharge
      surveys, a district nurse survey, and service user focus groups. All data were
      collectively analysed within a structure-process-outcome framework. Findings
      demonstrate that given adequate and appropriate support, education, training and
      clinical preparation, district nurses are effective and willing providers of care
      for people with HIV disease. However, there are problems in care coordination,
      discharge planning and accessing resources. At its best, community nursing is
      providing individualized, holistic and comprehensive care packages, but practice
      in both acute and primary care settings was not always effective.

PMID- 29324160
TI  - Influence of nurse gender on the use of silence, touch and humour.
AB  - A combination of data gathering approaches, i.e. conversation, observation and
      narrative exchange, were used to study the beliefs and actions of exemplary
      nurses. The data were analyzed using hermeneutic phenomenology and grounded
      theory methods and the findings revealed three major themes: dialogue in silence,
      mutual touch and sharing the lighter side of life. Participants in the study were
      chosen by peer nomination and reputational sampling and included both genders.
      The results showed a contrast in the way that exemplary males and females used
      silence, touch and humour in their practice. More specifically, compared with the
      women in the group, the men used silence to achieve different purposes, tended
      towards non-physical touch and used different forms of humour. This paper
      presents an introductory examination of the influence of nurse gender on the use
      of silence, touch and humour.

PMID- 29324161
TI  - Complementary therapies in cancer care: an NHS approach.
AB  - Complementary therapies are increasingly being used worldwide as a method of
      supporting people living with cancer. They offer improved quality of life,
      symptomatic control and self-help. There are established centres for
      complementary therapies in the UK; one such establishment is the Royal London
      Homoeopathic Hospital NHS Trust. This article describes the complementary cancer
      therapy programme offered at the RNHH. The programme includes homoeopathy,
      Iscador therapy, acupuncture, aromatherapy massage, Shiatsu, reflex zone therapy,
      relaxation and visualization training and breathing awareness classes. Other more
      conventional forms of assistance, including dietary advice, physiotherapy,
      occupational therapy and psychological support, are also offered. All therapies
      are advised according to individual need. Several case studies are presented to
      illustrate the use of the programme and its benefits.

PMID- 29324163
TI  - Psychological reactions to cancer recurrence.
AB  - The issue of fear of cancer recurrence in patients is poorly understood despite
      being acknowledged as important by nurses. Patients report feeling more emotional
      distress when a recurrence of their cancer recurs than at initial diagnosis. Many
      patients think that they have overcome the cancer and are bitterly disappointed
      when a recurrence is diagnosed. Courage is a theme that is present in many
      conversations with relatives and friends of cancer patients. This may inhibit the
      patient's need to express his/her distress and disappointment about the
      recurrence. If the patient's feelings cannot be expressed with the family, the
      nursing and medical staff need to work with the patient to allow him/her to
      explore these areas. This review paper draws together some significant findings
      that will assist oncology nurses when caring for patients with cancer.

PMID- 29324162
TI  - Nurses' perceptions of palliative care nursing.
AB  - This exploratory study using a survey design sought to investigate nurses'
      perceptions of palliative care nursing before and after participating in a 60
      hour continuing education programme. The 26 participants, from various nursing
      backgrounds, were enrolled on a joint university/hospital course which used a
      problem-based learning approach. During the course introduction, demographic
      data, together with descriptions of the students' perception/understanding of
      palliative care nursing, were obtained. Students' perceptions became the sole
      focus of the post-course study. Qualitative responses were analysed thematically
      and the remainder were analysed descriptively. The results suggest that those who
      undertook the course were beginning to move from a focus on carrying out nursing
      care to a deeper awareness of the possibilities of simply being with a patient.
      Other implications of the study were that palliative care educational programmes
      should be structured and taught in ways which help students reconceptualize the
      human person more holistically. Other factors emerged that were related to the
      physical environment of care and the wellbeing of staff in the practice setting.

PMID- 29324164
TI  - Management of lymphoedema: a developing specialism in nursing?
AB  - Although there is a long tradition of complex physical treatment of lymphoedema
      in continental Europe, it is only in the past decade that this approach has been
      introduced to Britain. During the 1980s, there was a gradual increase in the
      number of healthcare professionals, in particular nurses, offering treatment
      alongside their existing responsibilities. In the last 2 years, however, there
      has been a significant increase in the number of professionals specializing in
      the management of lymphoedema. Is the management of lymphoedema evolving as a
      specialism? This paper considers the concept of specialism and relates it to the
      development of lymphoedema management in Britain. Parallels with the development
      of an established nursing specialty are also explored.

PMID- 29324167
TI  - Research directions in palliative care nursing.
AB  - One of the most heartening aspects of palliative care and, in particular, the
      nursing contribution, is the rapid expansion of research activity directly
      pertinent to patients and their families. The courage of many research nurses in
      asking penetrating and sensitive questions is admirable. As they have often
      worked in the area and have the relevant skills, it is possible for nurses to
      identify important issues and explore them in a directly applicable way.

PMID- 29324165
TI  - Reflective practice: linking theory and practice in palliative care nursing.
AB  - Reflection is a method of learning and teaching nursing through critical analysis
      of experience. In this study the illuminative research approach is used with
      students on a care of the dying course (at diploma level) to explore the benefits
      of reflective practice. The study concludes that the nurses showed an increase in
      critical thinking, listening and observation skills, and awareness of knowledge
      in-use as a result of reflective learning and practice.

PMID- 29324168
TI  - Caring for dying Jewish people in a multicultural/religious society.
AB  - Despite an increased emphasis on racial awareness in health-care settings,
      religious customs that disrupt routines still unsettle nurses and other health
      workers. Providing education about the beliefs of different ethnic minorities and
      the significance for the different parties of practising specific death-related
      rituals could both prepare nurses for what they may encounter and increase their
      understanding of the responses of patients and their relatives. This article
      explores Jewish beliefs and practices relating to caring for dying and recently
      deceased people as an example of such death-related rituals. It is suggested that
      nurses should not be afraid of asking direct questions about levels of religious
      observance of the relatives of the dying Jewish person. Good communication skills
      and an openness to accept differences are essential if nurses are to respond
      appropriately to reduce the distress bereaved people from ethnic minorities
      experience when carrying out religious practices.

PMID- 29324169
TI  - Absence and Need for Fatigue Risk Management in Emergency Medical Services.

PMID- 29324170
TI  - Letter from the Editor.

PMID- 29324172
TI  - Human Vaccines & Immunotherapeutics: News.

PMID- 29324174
TI  - R. J. Michael Fry, MD 1925-2017.

PMID- 29324176
TI  - Resilience and Action in a Challenging Time for LGBT Rights.

PMID- 29324175
TI  - Radiation- and Age-Associated Changes in Peripheral Blood Dendritic Cell
      Populations among Aging Atomic Bomb Survivors in Japan.
AB  - Previous immunological studies in atomic bomb survivors have suggested that
      radiation exposure leads to long-lasting changes, similar to immunological aging
      observed in T-cell-adaptive immunity. However, to our knowledge, late effects of
      radiation on dendritic cells (DCs), the key coordinators for activation and
      differentiation of T cells, have not yet been investigated in humans. In the
      current study, we hypothesized that numerical and functional decreases would be
      observed in relationship to radiation dose in circulating conventional DCs (cDCs)
      and plasmacytoid DCs (pDCs) among 229 Japanese A-bomb survivors. Overall, the
      evidence did not support this hypothesis, with no overall changes in DCs or
      functional changes observed with radiation dose. Multivariable regression
      analysis for radiation dose, age and gender effects revealed that total DC counts
      as well as subpopulation counts decreased in relationship to increasing age.
      Further analyses revealed that in women, absolute numbers of pDCs showed
      significant decreases with radiation dose. A hierarchical clustering analysis of
      gene expression profiles in DCs after Toll-like receptor stimulation in vitro
      identified two clusters of participants that differed in age-associated
      expression levels of genes involved in antigen presentation and
      cytokine/chemokine production in cDCs. These results suggest that DC counts
      decrease and expression levels of gene clusters change with age. More than 60
      years after radiation exposure, we also observed changes in pDC counts associated
      with radiation, but only among women.

PMID- 29324173
TI  - The Risk of Deterioration in GCS13-15 Patients with Traumatic Brain Injury
      Identified by Computed Tomography Imaging: A Systematic Review and Meta-Analysis.
AB  - The optimal management of mild traumatic brain injury (TBI) patients with
      injuries identified by computed tomography (CT) brain scan is unclear. Some
      guidelines recommend hospital admission for an observation period of at least 24
      h. Others argue that selected lower-risk patients can be discharged from the
      Emergency Department (ED). The objective of our review and meta-analysis was to
      estimate the risk of death, neurosurgical intervention, and clinical
      deterioration in mild TBI patients with injuries identified by CT brain scan, and
      assess which patient factors affect the risk of these outcomes. A systematic
      review and meta-analysis adhering to PRISMA standards of protocol and reporting
      were conducted. Study selection was performed by two independent reviewers. Meta
      analysis using a random effects model was undertaken to estimate pooled risks
      for: clinical deterioration, neurosurgical intervention, and death. Meta
      regression was used to explore between-study variation in outcome estimates using
      study population characteristics. Forty-nine primary studies and five reviews
      were identified that met the inclusion criteria. The estimated pooled risk for
      the outcomes of interest were: clinical deterioration 11.7% (95% confidence
      interval [CI]: 11.7%-15.8%), neurosurgical intervention 3.5% (95% CI: 2.2%-4.9%),
      and death 1.4% (95% CI: 0.8%-2.2%). Twenty-one studies presented within-study
      estimates of the effect of patient factors. Meta-regression of study
      characteristics and pooling of within-study estimates of risk factor effect found
      the following factors significantly affected the risk for adverse outcomes: age,
      initial Glasgow Coma Scale (GCS), type of injury, and anti-coagulation. The
      generalizability of many studies was limited due to population selection. Mild
      TBI patients with injuries identified by CT brain scan have a small but
      clinically important risk for serious adverse outcomes. This review has
      identified several prognostic factors; research is needed to derive and validate
      a usable clinical decision rule so that low-risk patients can be safely
      discharged from the ED.

PMID- 29324177
TI  - Tobacco Use Among Adults by Sexual Orientation: Findings from the Population
      Assessment of Tobacco and Health Study.
AB  - PURPOSE: The aim of this study was to characterize lifetime tobacco use across
      two measures of sexual orientation and six types of tobacco products. METHODS: We
      conducted a cross-sectional analysis of the Population Assessment of Tobacco and
      Health (Wave 1, 2013-2014, USA) to estimate the prevalence of tobacco use
      (cigarettes, e-cigarettes, cigars, pipes, hookah, and smokeless) stratified by
      gender (men/women), age (< 25/>= 25 years old), and sexual orientation. Sexual
      orientation was operationalized as sexual identity and sexual attraction.
      RESULTS: Younger lesbian/gay and bisexual women had higher relative odds of
      experimental use of all six tobacco products compared to heterosexual women,
      whereas lesbian/gay and bisexual women in both age groups had higher odds of
      regular use of cigarettes, e-cigarettes, cigars, and hookah than heterosexual
      women. Younger gay men (but not older gay men) had higher relative odds of
      experimental and regular use of cigarettes compared to heterosexual men. Older
      gay men had higher odds of experimental e-cigarette and hookah use, but lower
      odds of regular cigar and experimental/regular smokeless tobacco use. Measures of
      sexual orientation identity and sexual attraction resulted in similar estimates
      of tobacco use with noted differences in those who identified as "something
      else," as well as among those who indicated asexual attraction. CONCLUSION: Our
      findings reflect a complex relationship between sexual orientation and tobacco
      use. Gender-based and product-specific approaches to tobacco prevention and
      control efforts are needed to address the high use of tobacco among sexual
      minority women.

PMID- 29324178
TI  - Sex Venue-Based Network Analysis to Identify HIV Prevention Dissemination Targets
      for Men Who Have Sex with Men.
AB  - PURPOSE: The aim of this study was to identify sex venue-based networks among men
      who have sex with men (MSM) to inform HIV preexposure prophylaxis (PrEP)
      dissemination efforts. METHODS: Using a cross-sectional design, we interviewed
      MSM about the venues where their recent sexual partners were found. Venues were
      organized into network matrices grouped by condom use and race. We examined
      network structure, central venues, and network subgroups. RESULTS: Among 49
      participants, the median age was 27 years, 49% were Black and 86% reported
      condomless anal sex (ncAS). Analysis revealed a map of 54 virtual and physical
      venues with an overlap in the ncAS and with condom anal sex (cAS) venues. In the
      ncAS network, virtual and physical locations were more interconnected. The ncAS
      venues reported by Blacks were more diffusely organized than those reported by
      Whites. CONCLUSION: The network structures of sex venues for at-risk MSM differed
      by race. Network information can enhance HIV prevention dissemination efforts
      among subpopulations, including PrEP implementation.

PMID- 29324179
TI  - Development and validation of an LC-MS/MS method for the quantification of
      tiamulin, trimethoprim, tylosin, sulfadiazine and sulfamethazine in medicated
      feed.
AB  - A new multi-compound method for the analysis of veterinary drugs, namely
      tiamulin, trimethoprim, tylosin, sulfadiazine and sulfamethazine was developed
      and validated in medicated feeds. After extraction, the samples were centrifuged,
      diluted in Milli-Q water, filtered and analysed by high performance liquid
      chromatography coupled to tandem mass spectrometry. The separation of the
      analytes was performed on a biphenyl column with a gradient of 0.1% formic acid
      in acetonitrile and 0.1% formic acid in Milli-Q water. Quantitative validation
      was done in accordance with the guidelines laid down in European Commission
      Decision 2002/657/EC. Method performances were evaluated by the following
      parameters: linearity (R2 < 0.99), precision (repeatability <14% and within
      laboratory reproducibility <24%), recovery (73.58-115.21%), sensitivity, limit of
      detection (LOD), limit of quantification (LOQ), selectivity and expanded
      measurement uncertainty (k. = 2). The validated method was successfully applied
      to the 2 medicated feeds obtained from the interlaboratory studies and feed
      manufactures from Spain in August 2017. In these samples, tiamulin, tylosin and
      sulfamethazine were detected at the concentration levels declared by the
      manufacturers. The developed method can therefore be successfully used to
      routinely control the content and homogeneity of these antibacterial substances
      in medicated feed. Abbreviations AAFCO - Association of American Feed Control
      Officials; TYL - tylosin; TIAM - tiamulin fumarate; TRIM - trimethoprim; SDZ -
      sulfadiazine; SMZ - sulfamethazine; UV - ultraviolet detector; FLD - fluorescence
      detector; HPLC - high performance liquid chromatography; MS/MS - tandem mass
      spectrometry; LOD - limit of detection; LOQ - limit of quantification; CV -
      coefficient of variation; SD - standard deviation; U - uncertainty.

PMID- 29324181
TI  - Effective antibiotic stewardship in spinal cord injury: Challenges and a way
      forward.
AB  - Context Antibiotic stewardship, defined as a multidisciplinary program to reduce
      the misuse of antibiotics, and in turn, antibiotic resistance, is a high
      priority. Persons with spinal cord injury/disorder (SCI/D) are vulnerable to
      receiving multiple courses of antibiotics over their lifetime given frequent
      healthcare exposure, and have high rates of bacterial infection with multi-drug
      resistant organisms. Additional challenges to evaluating appropriate use of
      antibiotics in this population include bacterial colonization in the urine and
      the differences in the presenting signs and symptoms of infection. Therefore,
      Veterans Health Administration (VHA) facilities with SCI/D centers need effective
      antibiotic stewardship programs. Results We analyzed the results of a 2012 VHA
      wide survey evaluating available antibiotic stewardship resources, and compared
      the resources present at facilities with SCI/D (n=23) versus non-SCI/D facilities
      (n=107). VHA facilities with SCI/D centers are more likely to have components of
      an antibiotic stewardship program that have led to reduced antibiotic use in
      previous studies. They are also more likely to have personnel with infectious
      diseases training. Conclusion VHA facilities with SCI/D centers have the
      resources needed for antibiotic stewardship. The next step will be to determine
      how to implement effective antibiotic stewardship tailored for this patient care
      setting.

PMID- 29324180
TI  - Who Cares about Sleep in Older Adults?

PMID- 29324182
TI  - Recent Advances in Solid-State Nuclear Magnetic Resonance Spectroscopy.
AB  - The sensitivity of nuclear magnetic resonance (NMR) spectroscopy to the local
      atomic-scale environment offers great potential for the characterization of a
      diverse range of solid materials. Despite offering more information than its
      solution-state counterpart, solid-state NMR has not yet achieved a similar level
      of recognition, owing to the anisotropic interactions that broaden the spectral
      lines and hinder the extraction of structural information. Here, we describe the
      methods available to improve the resolution of solid-state NMR spectra and the
      continuing research in this area. We also highlight areas of exciting new and
      future development, including recent interest in combining experiment with
      theoretical calculations, the rise of a range of polarization transfer techniques
      that provide significant sensitivity enhancements, and the progress of in situ
      measurements. We demonstrate the detailed information available when studying
      dynamic and disordered solids and discuss the future applications of solid-state
      NMR spectroscopy across the chemical sciences.

PMID- 29324183
TI  - Technologies for Measuring Pharmacokinetic Profiles.
AB  - The creation of a pharmacokinetic (PK) curve, which follows the plasma
      concentration of an administered drug as a function of time, is a critical aspect
      of the drug development process and includes such information as the drug's
      bioavailability, clearance, and elimination half-life. Prior to a drug of
      interest gaining clearance for use in human clinical trials, research is
      performed during the preclinical stages to establish drug safety and dosing
      metrics from data obtained from the PK studies. Both in vivo animal models and in
      vitro platforms have limitations in predicting human reaction to a drug due to
      differences in species and associated simplifications, respectively. As a result,
      in silico experiments using computer simulation have been implemented to
      accurately predict PK parameters in human studies. This review assesses these
      three approaches (in vitro, in vivo, and in silico) when establishing PK
      parameters and evaluates the potential for in silico studies to be the future
      gold standard of PK preclinical studies.

PMID- 29324184
TI  - Effects of nonsteroidal anti-inflammatory drugs on serum proinflammatory
      cytokines in the treatment of ankylosing spondylitis.
AB  - OBJECTIVE: This study was conducted to investigate the correlation between serum
      levels of proinflammatory cytokines and the clinical efficacy of nonsteroidal
      anti-inflammatory drugs (NSAIDs) in patients with ankylosing spondylitis (AS).
      METHODS: A total of 148 patients with AS were selected and received NSAID
      treatment. ELISA was used to assess cytokine levels, and patients were assigned
      into the following groups: positively effective; effective; moderately effective;
      and ineffective. Spearman and Pearson correlation analyses were used for
      correlation analysis. RESULTS: The erythrocyte sedimentation rates (ESR), C
      reactive protein (CRP) levels, and immunoglobulin A (IgA) levels of the case
      group after NSAID treatment were markedly lower than those before NSAID
      treatment. After treatment, the levels of interleukin (IL)-6, IL-17, and tumor
      necrosis factor (TNF)-alpha were markedly reduced, while IL-10 levels increased
      in the positively effective, effective, and moderately effective groups, and IL
      12 levels decreased in the positively effective and effective groups. In
      addition, the levels of IL-6 and TNF-alpha were correlated with a greater number
      in the efficacy indexes and clinical parameters, followed by IL-10 levels, while
      the levels of IL-17 and IL-12 had relatively weaker correlations with these
      indexes and parameters. CONCLUSION: NSAIDs could promote the clinical efficacy of
      treatment for ankylosing spondylitis by regulating serum levels of
      proinflammatory cytokines.

PMID- 29324185
TI  - Ventilator Circuit Trash May Be a Research Treasure.

PMID- 29324187
TI  - Shock-associated Cardiac Arrest: Vasodilator Therapy May Help.

PMID- 29324186
TI  - Impact of sodium citrate ingestion during recovery after dehydrating exercise on
      rehydration and subsequent 40-km cycling time-trial performance in the heat.
AB  - The purpose of this study was to assess the impact of sodium citrate (CIT)
      ingestion (600 mg.kg-1) during recovery from dehydrating cycling exercise (DE) on
      subsequent 40-km cycling performance in a warm environment (32  degrees C).
      Twenty male nonheat-acclimated endurance athletes exercised in the heat until 4%
      body mass (BM) loss occurred. After 16 h recovery with consumption of water ad
      libitum and prescribed diet (evening meal 20 kcal.kg-1, breakfast 12 kcal.kg-1)
      supplemented in a double-blind, randomized, crossover manner with CIT or placebo
      (PLC), they performed 40-km time-trial (TT) on a cycle ergometer in a warm
      environment. During recovery greater increases in BM and plasma volume (PV)
      concomitant with greater water intake and retention occurred in the CIT trial
      compared with the PLC trial (p < 0.0001). During TT there was greater water
      intake and smaller BM loss in the CIT trial than in the PLC trial (p < 0.05) with
      no between-trial differences (p > 0.05) in sweat loss, PV decrement, ratings of
      perceived exertion, or TT time (CIT 68.10 +/- 3.28 min, PLC 68.11 +/- 2.87 min).
      At the end of TT blood lactate concentration was higher (7.58 +/- 2.44 mmol.L-1
      vs 5.58 +/- 1.32 mmol.L-1; p = 0.0002) and rectal temperature lower (39.54 +/-
      0.50  degrees C vs 39.65 +/- 0.52  degrees C; p = 0.033) in the CIT trial than in
      the PLC trial. Compared with pre-DE time point, PV had decreased to a lower level
      in the PLC trial than in the CIT trial (p = 0.0001). In conclusion, CIT enhances
      rehydration after exercise-induced dehydration but has no impact on subsequent 40
      km cycling TT performance in a warm uncompensable environment.

PMID- 29324188
TI  - "I'm Doing the Best That I Can for Her": Infant-Feeding Decisions of Mothers
      Receiving Medication-Assisted Treatment for an Opioid Use Disorder.
AB  - BACKGROUND: Several professional health organizations have made statements
      endorsing the safety of breastfeeding for women taking medication-assisted
      treatment for an opioid use disorder. Yet, breastfeeding initiation rates for
      this population are approximately 50% lower than the general United States'
      population. Furthermore, little is known about what influences the infant-feeding
      decisions of these women. Research aim: This study aimed to describe what
      influences the infant-feeding decisions of women taking medication-assisted
      treatment for an opioid use disorder. METHODS: Qualitative description was used.
      We conducted semistructured, individual interviews with mothers ( N = 8) who were
      receiving medication-assisted treatment during the postpartum period. We analyzed
      our data using thematic analysis. RESULTS: We identified two themes: (a) what I
      heard about breastfeeding, and (b) doing what I feel is best for my baby. What I
      heard about breastfeeding reflects the information and misinformation that women
      received about breastfeeding. Doing what I feel is best for my baby describes the
      inner conflict that the women experienced. Most of the women in this study
      desired to breastfeed; however, all women reported that the social stigma
      surrounding methadone use strongly influenced their infant-feeding decision.
      CONCLUSION: This study sheds new light on what influences the infant-feeding
      decisions of women taking medication-assisted treatment and represents an initial
      step toward the development of targeted interventions to improve breastfeeding
      rates for this unique population.

PMID- 29324189
TI  - Is Cisatracurium the Neuromuscular Blocking Agent of Choice in Acute Respiratory
      Distress Syndrome?

PMID- 29324191
TI  - STUDIES ON THE LIFE HISTORY OF TWO CORAL-EATING NUDIBRANCHS OF THE GENUS
      PHESTILLA.
AB  - 1. The complete life cycles of two coral-eating aeolid nudibranchs, Phestilla
      melanobranchia Bergh, 1874 and Phestilla sibogae Bergh, 1905, are described.
      Information on their life histories includes developmental stages and timing,
      duration of the veliger stage, veliger behavior, factors necessary for settling
      and metamorphosis, and adult growth rates, fecundity and longevity. The life
      cycles of the two Phestilla are similar and their physical and behavioral
      differences are related to the characteristics of their respective coral prey. 2.
      P. melanobranchia has planktotrophic development, is negatively phototactic when
      ready to settle, requires close proximity to living dendrophylliid coral tissue
      for metamorphosis and has a generation time from egg to egg of 60 days. The
      dendrophylliid corals on which P. melanobranchia feeds are small, patchy and
      photonegative in distribution. 3. P. sibogae which has now been under serial
      cultivation for four years, has lecithotrophic development, is positively
      phototactic when ready to settle, requires only a chemical factor from living
      Porites tissue for metamorphosing and has a generation time of 38 days. The
      Porites corals which P. sibogae feeds on are large, very common and photopositive
      in distribution. 4. Differences in predation pressure and prey tissue utilization
      efficiency are proposed as factors influencing the evolution of a significantly
      faster generation time in Phestilla sibogae than in the closely related P.
      melanobranchia.

PMID- 29324192
TI  - THE ESCAPE OF VELIGERS FROM THE EGG CAPSULES OF NASSARIUS OBSOLETUS AND NASSARIUS
      TRIVITTATUS (GASTROPODA, PROSOBRANCHIA).
AB  - 1. The loosening of the egg capsule plug prior to escape of the veligers is shown
      to be chemically mediated in Nassarius obsoletus and N. trivittatus. 2. The
      hatching substance is not produced continuously during development, but rather in
      a short pulse beginning just prior to hatching and ending within 4 hours of
      escaping from the capsule, for N. obsoletus. 3. The hatching substance produced
      by the embryos of one species is effective only on the capsule plugs of that
      species, for the two species studied. 4. The substance is functionally short
      lived, at room temperature in sea water, losing its potency within three hours
      after its secretion by N. obsoletus. 5. The observed rate at which N. obsoletus
      veligers leave their egg capsules is shown to be in close agreement with the rate
      predicted from an equation assuming random movements of individuals within the
      capsules.

PMID- 29324193
TI  - STAGES IN THE LIFE HISTORY OF A SYMBIOTIC ZOOXANTHELLA IN PELLETS EXTRUDED BY ITS
      HOST AIPTASIA TAGETES (DUCH. AND MICH.) (COELENTERATA, ANTHOZOA).
AB  - 1. Various morphological stages in the life history of the zooxanthella symbiotic
      with Aiptasia tagetes have been identified in pellets extruded by the actinian
      host. One of the stages is a motile zoospore. 2. This zoospore resembles that
      observed by Kawaguti (1944) and differs from those identified in axenic cultures
      of G. microadriaticum in containing a large accumulation body. Suggestions are
      made as to the significance of this difference. 3. It is very likely that the
      zoospore is an infective stage in the life history of the zooxanthella. 4. There
      is some evidence to suggest that indirect infection of hosts by zooxanthellae is
      also possible.

PMID- 29324194
TI  - INVESTIGATION ON THE ECOLOGY AND RESPIRATORY RESPONSES OF THE HEMICHORDATE
      PTYCHODERA FLAVA TO TIDAL CYCLES AND SALINITY CHANGES.
AB  - 1. Some aspects of the ecology and respiratory physiology of Ptychodera flava
      have been studied. 2. Increase in body weight involves a decrease in the rate of
      oxygen consumption. At high tides, the rates of oxygen uptake of nonbreeding P.
      flava are 0.7629 (smallest) and 0.3363 (largest) in ml/g/hr. At high tides,
      mature and spawning female rates are 6.732 (smallest) and 0.8877 (largest)
      ml/g/hr. Rate of oxygen uptake is a function both of body size and of maturity
      stage in P. flava. 3. Respiratory responses of 15 specimens of P. flava fell into
      three classes: 1, showing a rhythm synchronized with tidal phases; 2, showing a
      tidal rhythm with additional peaks during low tides; or 3, with no detectable
      rhythm. 4. P. flava reacts to lowered salinity by showing a sudden rise in
      respiration. The sustained level of respiration is subsequently a little higher
      than in normal sea water. 5. The deep-seated tidal rhythm shows variations, and
      it is suggested that locomotor activity, spawning, temperature, and salinity may
      all be factors involved.

PMID- 29324195
TI  - ULTRASTRUCTURE OF THE PIGMENTARY SYSTEM AND CHROMATOPHOROTROPIC ACTIVITY IN LAND
      ISOPODS.
AB  - 1. The question of the absence of physiological color change in terrestrial
      isopods was investigated with three species of land isopods (Armadillidium
      vulgare, Porcellio laevis and Pardioniscus argentinus) and a marine species
      (Ligia exotica) as reference. 2. The young and adults of the terrestrial isopods
      do not change color when exposed to dark or light conditions, nor to white or
      black backgrounds. 3. Light microscopy showed that the pigmentary System of the
      terrestrial isopods is an apparently syncytial net work containing a dark brown
      pigment. 4. Electron microscopy revealed that the pigmentary network is only
      apparently syncytial; its elements are merely contiguous. As compared to
      chromatophores of Ligia, the elements of the network of land isopods are much
      poorer in smooth endoplasmic reticulum and have no microtubules. 5. Homogenates
      of sinus gland and of nerve cord from land isopods induced pigment dispersion in
      melanophores from Ligia exotica; the effect was proportional to concentration of
      homogenate. Such extracts had no effect on melanophores of darkened animals. 6.
      The results obtained with the terrestrial species indicate that these isopods can
      produce chromatophorotropic-active substances (pigment-dispersing principles)
      despite their lack of physiological color change. 7. The lack of physiological
      color change is associated with the disappearance or absence of microtubules and
      reduction of endoplasmic reticulum, although there is no substantial evidence
      that these organelles play a role in pigment migration.

PMID- 29324196
TI  - THE MATERNAL POUCH AND DEVELOPMENT IN THE MARSUPIAL FROG GASTROTHECA RIOBAMBAE
      (FOWLER).
AB  - The pouch of Gastrotheca riobambae (Fowler) serves as the location for
      development of the embryo up to the swimming tadpole stage. The pouch lies under
      the dorsal integument of the female and, in nonpregnant females, is similar to
      the integument. Pregnancy is accompanied by increased vascularization of the
      pouch. Blood capillaries from the corium become closely associated with the
      epithelial lining of the pouch, and vascularized outgrowths of the pouch
      partially envelop the embryos. Embryonic development in the pouch is
      characterized by the presence of peculiar gills, the highly vascularized "bell
      gills," which expand and flatten against the inner surface of the jelly capsule,
      forming an individual sac about each embryo and thus establishing a close
      relationship between embryonic and maternal circulatory systems. After birth of
      the tadpoles, the gills are soon resorbed and there is regression of the
      vascularization of the pouch. Reorganization of the tissue and shedding of the
      lining epithelium restore the pouch to the condition found in the nonpregnant
      female.

PMID- 29324197
TI  - SUMMER ABUNDANCE AND ECOLOGY OF ZOOPLANKTON IN THE GULF STREAM.
AB  - We have described the results of laboratory analyses of 42 horizontal tows using
      a Clarke-Bumpus plankton sampler with a 100 u emmesh net in the Gulf Stream.
      Classifications of 20 zooplankton taxa have been made for the 42 hauls. Calanoids
      dominate the hauls. It was found that the zooplankton population distribution and
      density varied considerably from haul to haul, but there was no consistent
      buildup or depletion of population with progress of the flow north in the Gulf
      Stream. These biological arguments reinforce previous conjectures that there is a
      geostrophically-balanced inflow of continental shelf and Labrador Sea water that
      gradually mixes with the Gulf Stream water mass. These inflows provide sources of
      zooplankton and phytoplankton to the Gulf Stream as it progresses northward.
      Also, an ecological analysis of the Gulf Stream indicates that the dry organic
      matter is over an order of magnitude below that which is theoretically possible.

PMID- 29324198
TI  - COMPARATIVE CHEMOSENSITIVITY TO AMINO ACIDS AND THEIR ROLE IN THE FEEDING
      ACTIVITY OF BATHYPELAGIC AND LITTORAL CRUSTACEANS.
AB  - 1. Feeding response exhibition in five marine crustaceans was observed in the
      presence of a range of concentrations of an amino acid mixture composed of equal
      parts DL alpha arnino-n-butyric acid, L-glutamic acid and taurine.
      Gnathophausiaingens, Pleuroncodes planipes, and Cancer antennarius displayed
      behavioral thresh olds of between 10-10 and 10-12 M; Spirontocaris taylori and
      Pagurus hirsutiusculus displayed thresholds between 10-7 and 10-9 M. 2.
      Electrophysiological response thresholds to the amino acid mixture were examined
      in G. ingens and C. antennarius. The antennular and dactyl receptors of G. ingens
      displayed thresholds of 10-7 and 10-8 M respectively. Maxilliped and dactyl
      receptors of C. antennarius both displayed a threshold of 5 x 10-5 M. 3.
      Panulirus interruptus antennule receptors displayed a degree of specificity to
      mono- and dicarboxylic amino acids.

PMID- 29324199
TI  - COMPARISON OF CHROMATOPHOROTROPINS FROM THE HORSESHOE CRAB LIMULUS POLYPHEMUS,
      AND THE FIDDLER CRAB, UCA PUGILATOR 1.
AB  - 1. Extracts of the central nervous system of the horseshoe crab, Limulus
      polyphemus, were assayed for chromatophorotropic activity on the fiddler crab,
      Uca pugilator. The extracts caused pigment dispersion in the melanophores and
      pigment concentration in the leucophores but had no effect on the erythrophores.
      2. The ethanol-soluble and 95% methanol:chloroform (2:1)-soluble fractions of the
      central nervous system from the horseshoe crab evoked melanin-dispersing and
      white pigment-concentrating responses which had larger amplitudes and longer
      durations than did the responses caused by extracts prepared directly in saline.
      3. Neither gel filtration nor acetone fractionation was effective in separating
      the melanin-dispersing activity from the white pigment-concentrating activity in
      extracts of the central nervous system of the horseshoe crab. These responses
      appear to be caused by either the same molecule or by different substances having
      similar elution patterns from Bio-Gel P-6. 4. Extracts of the eyestalk of the
      fiddler crab were fractionated on Bio-Gel P-6. The melanin-dispersing, white
      pigment-dispersing and red pigment-dispersing activities were eluted with an Rf
      of 0.57, the same value as that of the major peaks of melanin-dispersing and
      white pigment-concentrating activities from the central nervous system of the
      horseshoe crab. In contrast, the white pigment-concentrating and red pigment
      concentrating activities of the fiddler crab separated from the pigment
      dispersing activities, having been eluted later from the column of Bio-Gel P-6
      with an Rf of 0.28. 5. The chromatophorotropic material in the central nervous
      system of the horseshoe crab is more closely related to the melanin-dispersing
      material of the fiddler crab than to the white pigment-concentrating hormone of
      the fiddler crab. 6. The chromatophorotropins in the central nervous system of
      the horseshoe crab and the radial nerves of the sea star differ from each other
      in their elution patterns from a column of Bio-Gel P-6 and in the chromatophore
      responses they evoke in the fiddler crab.

PMID- 29324200
TI  - TEMPORAL PATTERNS OF SEXUAL AND ASEXUAL REPRODUCTION IN THE COLONIAL ASCIDIAN
      METANDROCARPA TAYLORI HUNTSMAN.
AB  - 1. Metandrocarpa taylori Huntsman (1912) is an ovoviviparous colonial ascidian
      with separate zooids connected by a common basal tunic, which reproduces
      asexually by pallial budding. 2. Specimens in collections from field populations
      show maximum periods of sexual reproduction during the summer months. Although
      approximately 80% of the 1961 summer samples were reproductively active during
      this period, sexual reproduction continued during the remainder of the year with
      no less than 30% of the population active at any time. Eggs and testes develop
      simultaneously within the individual zooids. 3. Asexual reproduction was
      quantitatively studied in colonies cultured in the intertidal zone. Budding rates
      are lowest during the summer and continue at a high level during the remainder of
      the year. These rates are not dependent upon the size or age of the colony, but
      do derive from variations in rates at which successive bud generations follow one
      another and from the number of bud offspring produced by each zooid. 4. Although
      the two modes of reproduction are not mutually exclusive, it is clear that one
      form predominates in activity during any single season. 5. There is a general
      direct relationship between sexual reproductive activity and ocean temperature.
      There is little correlation of reproductive activity with food supply, since
      either phytoplankton or suspended organic detritus are abundant in Monterey Bay
      all year.

PMID- 29324201
TI  - THE MARINE ENCHYTRAEIDAE (ANNELIDA, OLIGOCHAETA) OF THE EASTERN COAST OF NORTH
      AMERICA WITH NOTES ON THEIR GEOGRAPHICAL DISTRIBUTION AND HABITAT.
AB  - 1. Marine Enchytraeidae from the Eastern coast of North America were examined.
      Six genera and thirteen species are reported, four genera and eleven species are
      new to the American continent. 2. One new genus and two new species are described
      on material received from the Biotic Census of the Systematics-Ecology Program at
      the Marine Biological Laboratory: Hemigrania nov. gen., Lumbricillus codensis
      nov. sp. and Marionina welchi nov. sp. Three species are included in the new
      genus: Hemigrania postclitellochaeta (Knollner, 1934), Hemigrania monochaeta
      (Michaelsen, 1888), Hemigrania principissae (Michaelsen, 1907); three species are
      related to Marionina welchi nov. sp.: Marionina subtilis (Ude, 1896), Marionina
      paucispina (Eisen, 1904) and Marionina normani (Michaelsen, 1907). 3. Marine
      Enchytraeidae are found in both littoral and sublittoral biotopes. Four
      categories of habitats are briefly described, (a) salt marshes, (b) the dirftline
      of seaweed deposit, (c) intertidal sand beaches, with well-sorted sediment and
      very small amounts of detritus, (d) the subtidal biotopes with very well-sorted
      sandy sediments. 4. The marine Enchytraeid fauna is composed of eurythermic cold
      water species, very abundant on the north eastern coast of North America (the
      Woods Hole region, Massachusetts), and also present under the warmer latitudes of
      the Beaufort region, North Carolina.

PMID- 29324202
TI  - HISTOCHEMICAL STUDY OF GUT NUTRIENT RESERVES IN RELATION TO REPRODUCTION AND
      NUTRITION IN THE SEA STARS, PISASTER OCHRACEUS AND PATIRIA MINIATA.
AB  - 1. Histochemical procedures indicate that in Pisaster ochraceus and Patiria
      miniata a diastase-labile carbohydrate occurs in small quantities as fine
      granules in the peritoneum and muscle of the gut, and in the columnar epithelia
      of the stomach and ducts of the pyloric caecae. A diastase-resistant carbohydrate
      occurs abundantly in the storage cells of the pyloric caeca, usually as a matrix
      surrounding large granules of protein. Neutral lipid droplets occur in small
      quantities in the columnar epithelium of the cardiac stomach and are abundant in
      the storage cells of the pyloric caeca. 2. In Pisaster the pyloric caeca increase
      in size from June to December and decrease in size during the spring at the time
      when the gonads are growing. The inverse size relationship suggests the
      withdrawal of material from the caeca for use by the gonads. The pyloric caeca of
      Patiria seem to remain fairly constant in size during the breeding cycle. 3. In
      both species prolonged starvation during the breeding period results in shrinkage
      of the pyloric caeca and reduction of the nutrient reserves to levels
      insufficient to support normal gonadal development. Starvation most markedly
      reduces the histochemically detectable carbohydrate in the pyloric caeca. Stomach
      lipid is reduced in both species, and most of the caecal lipid disappears in
      Patiria. Even after twenty months of starvation Pisaster specimens still showed
      considerable lipid in the caeca. 4. The connective tissue and mucus from most
      parts of the gut appeared to contain neutral and weakly acid mucopolysaccharide
      components or a single compound with both neutral and acid residues. Fine
      granules found at the apices of cells in certain regions of the stomach contain a
      more acid mucopolysaccharide. 5. The histochemical results correlate well with
      earlier biochemical data available for the two species.

PMID- 29324203
TI  - A NEW LILJEBORGIID AMPHIPOD (CRUSTACEA) FROM KERALA, INDIA.
AB  - A new gammaridean amphipod, Listriella similis is described in detail. This
      species shows resemblance to L. picta (Norman), L. diffusa J. L. Barnard and L.
      eriopisa J. L. Barnard, but can be easily distinguished by the shape of the third
      pleon epimeron and the appearance of the sixth segment of gnathopods 1 and 2. In
      the light of the present study, the observations of J. L. Barnard (1959) on the
      family Liljeborgiidae are critically examined. It is found that the three
      characters mentioned by him for distinguishing the three existing genera of the
      family, do not go together. Further, it is suggested that the 2-segmented
      accessory flagellum of antenna 1 in Listriella may serve as an additional
      character, differentiating it from Liljeborgia. A brief summary of the annual
      sequence in the salinity fluctuations of the Kayamkulam lake, where from the
      present species was obtained, is given. It is probable that the association of
      the animal with the algal communities of the bar mouth region of the lake affords
      some protection to it in the intertidal.

PMID- 29324204
TI  - LARVAL DEVELOPMENT OF PAGURUS LONGICARPUS SAY REARED IN THE LABORATORY. III.
      BEHAVIORAL RESPONSES TO SALINITY DISCONTINUITIES.
AB  - 1. Each zoeal instar of P. longicarpus was exposed to salinity discontinuities of
      varying magnitudes. Three distinct behavioral responses were observed: telson
      flips regardless of the magnitude of the discontinuity; downward swimming when
      the magnitude of the discontinuity was moderate; passive sinking when the
      magnitude of the discontinuity was extreme. 2. All zoeal instars avoided water
      with a salinity of ca. 200/00 or less, well within the range of salinity
      permitting complete development to the juvenile. 3. Avoidance of low salinity
      layers in stratified columns by Zoea I and II appeared to be a function of an
      absolute salinity (S?20-220/00) when the salinity of the lower layer (SL) was
      less than 250/00 and a function of salinity difference (DeltaS) when SL was
      greater than 250/00 (DeltaS?80/00 for Zoea I; DeltaS?50/00 for Zoea II).
      Avoidance of bow salinity layers by Zoea III and IV appeared to be a fuction of
      absolute salinity (S?200/00) regardless of SL over the range of SL tested. 4.
      Evidence is presented that the antennules and antennae may not be involved in
      detection of salinity discontinuities.

PMID- 29324205
TI  - BEHAVIORAL AND ELECTROPHYSIOLOGICAL STUDIES OF HYDRA. II. PACEMAKER ACTIVITY OF
      ISOLATED TENTACLES.
AB  - 1. Electrical potentials associated with coordinated contraction of the
      longitudinal muscles can be recorded from isolated tentacles of Hydra. In both H.
      pirardi and H. pseudoligactis these Tentacle Contraction Pulses (TCP's) occur
      chiefly in bursts, which are more frequent in H. pirardi. The bursts are
      approximately the same length in the two species but those of H. pirardi contain
      more pulses. 2. Inter-pulse interval lengths within a burst decrease but then
      lengthen again toward the end of the burst. Small segments of a tentacle produce
      the same pulse patterns as whole tentacles, indicating that there are a number of
      potential pacemakers with similar properties dispersed within a tentacle. 3.
      Strong illumination increases the burst frequency and the number of pulses per
      burst. Pulses of mechanical stimuli induce single TCP's and inhibit TCP bursts.
      Isolated tentacles habituate to repeated mechanical stimuli. Exposure of the
      tentacle to live or aqueous extracts of Artemia nauplii, or 10-5 M GSH inhibits
      TCP bursts and monophasic pulses are induced which are associated with asymmetric
      writhing movements.

PMID- 29324206
TI  - REMOVAL OF THE FERTILIZATION MEMBRANE OF FERTILIZED EGGS OF URECHIS CAUPO AND
      DEVELOPMENT OF "MEMBRANELESS" EMBRYOS.
AB  - It has been shown that the fertilization membrane of the Urechis embryo can be
      removed by treatment with a sucrose-EDTA solution. The resulting membraneless
      embryos appear to undergo nearly normal embryogenesis, differing from the
      controls only in shape, degree of motility and ability to form double-embryos.

PMID- 29324207
TI  - Oligometastatic Non-Small-Cell Lung Cancer: How Should We Define and Manage It?

PMID- 29324208
TI  - Solid Organ Transplantation in Patients With a History of Lymphoma.
AB  - There is an increasing number of long-term survivors of Hodgkin and non-Hodgkin
      lymphoma. These people may have a need for subsequent solid organ
      transplantation, often as a result of late effects of their lymphoma treatment.
      There is abundant literature demonstrating that patients with a history of
      lymphoma are appropriate candidates for solid organ transplantation. Long-term
      survival without relapse and with a functioning graft is possible. Patients with
      a history of post-transplantation lymphoproliferative disorders and patients who
      have received a prior hematopoietic stem-cell transplantation may also be
      candidates. Although high-level supporting evidence is not available, most
      guidelines recommend a waiting period of 2 to 5 years after lymphoma treatment
      before patients undergo solid organ transplantation. Each patient with a history
      of lymphoma requires a multidisciplinary approach and should be evaluated on a
      case-by-case basis before consideration of solid organ transplantation.

PMID- 29324209
TI  - Using Process Improvement Tools to Improve the Care of Patients With Neutropenic
      Fever in the Emergency Room.
AB  - PURPOSE: The purpose of this study was to improve the care of patients with
      neutropenic fever in an academic acute care hospital's emergency room (ER).
      METHODS: Using the define, measure, analyze, improve, control method, a two-phase
      project with three critical to quality metrics (reduction in time to antibiotic
      administration, increase in percentage of patients with neutropenic fever
      identified as an oncology emergency, and increase in patients cohorted on
      oncology units) was completed. Phase I consisted of implementation of best
      practices (ie, use of neutropenic fever protocol and order set, altering ER
      workflow, and educating patients and staff). In phase II, the team drew from
      cardiac and stroke alerts and response teams and implemented an innovative
      hospital-wide overhead neutropenic fever alert and an ER neutropenic fever
      response team. RESULTS: After implementing phase I interventions, the time to
      antibiotic administration decreased from a mean of 100 minutes at baseline to a
      mean of 67 minutes. After implementing phase II interventions, the mean decreased
      by 73%, from 100 minutes at baseline to 27 minutes. Furthermore, after phase II
      interventions, 89% of neutropenic patients were assigned an Emergency Severity
      Index of 2 and 88% were placed appropriately in a bed on the oncology floor on
      admission, compared with 11% and 74%, respectively, at baseline. CONCLUSION:
      Interventions were effective at improving three critical to quality metrics.
      Multiple iterations of the define, measure, analyze, improve, control cycle,
      together with new innovative interventions, were crucial to meeting project
      goals.

PMID- 29324210
TI  - Between the Rock and Hard Place: The Evaluation of a Patient With a History of
      Cancer for Solid Organ Transplantation.

PMID- 29324211
TI  - Solid Organ Transplantation in Selected Patients With a History of Lymphoma: Has
      the Time Come?

PMID- 29324213
TI  - JHL News.

PMID- 29324212
TI  - Managing Patients With Oligometastatic Non-Small-Cell Lung Cancer.
AB  - Metastatic lung cancer has long been considered incurable, with the goal of
      treatment being palliation. However, a clinically meaningful number of these
      patients with limited metastases (approximately 25%) are living long term after
      definitive treatment to all sites of active disease. These patients with so
      called oligometastatic disease likely represent a distinct clinical group who may
      possess a more indolent biology compared with their more widely metastatic
      counterparts. Hellman and Weichselbaum proposed the existence of the
      oligometastatic state, on the basis of the spectrum theory of cancer spread. The
      literature suggests that an oligometastatic state exists in patients with non
      small-cell lung cancer (NSCLC). This observation in the setting of rapidly
      evolving systemic therapies, including immune checkpoint inhibitors and an
      increasing number of targeted therapies, represents a unique clinical
      opportunity. Metastasis-directed therapies to address sites of disease include
      surgery (metastasectomy) and/or radiation therapy. Available evidence suggests
      that treating patients with limited or oligometastases may improve outcomes in a
      meaningful way; however, the majority of the randomized data includes patients
      with intracranial metastatic disease, and there are limited robust, randomized
      data available in the setting of NSCLC with only extracranial sites of metastatic
      disease. Ongoing randomized trials, including NRG-LU002 and the UK Conventional
      Care Versus Radioablation (Stereotactic Body Radiotherapy) for Extracranial
      Oligometastases trial, are aimed at evaluating this question further. One of the
      current limitations of aggressive treatment of oligometastatic NSCLC is the
      inability to accurately identify these patients before therapy, yet molecular
      markers, including microRNA profiles, are being investigated as a promising way
      to identify these patients.

PMID- 29324216
TI  - Self-Reported Cognitive Impairment Across Racial/Ethnic Groups in the United
      States, National Health Interview Survey, 1997-2015.
AB  - INTRODUCTION: The primary objectives of this study were 1) to examine trends of
      self-reported cognitive impairment among 5 major racial/ethnic groups during 1997
      2015 in the United States and 2) to examine differences in the trends across
      these groups. METHODS: Data were from the National Health Interview Survey
      (NHIS). The sample consisted of 155,682 people aged 60 or older. Respondents were
      asked to report whether any family member was "limited in any way because of
      difficulty remembering or because of experiencing periods of confusion."
      Race/ethnicity categories were non-Hispanic white, non-Hispanic black, Native
      American, Hispanic, and Asian. We applied hierarchical age-period-cohort cross
      classified random-effects models for the trend analysis. All analyses accounted
      for the complex survey design of NHIS. RESULTS: The overall rate of self-reported
      cognitive impairment increased from 5.7% in 1997 to 6.7% in 2015 (P for trend
      <.001). Among non-Hispanic white respondents, the rate increased from 5.2% in
      1997 to 6.1% in 2015 (slope = 0.14, P for trend <.001). We observed no
      significant trend in rate of cognitive impairment in other groups. After we
      controlled for covariates, we found that Asian (B = 0.31), non-Hispanic black (B
      = 0.37), Hispanic (B = 0.25), and Native American (B = 0.87) respondents were
      more likely than non-Hispanic white respondents to report cognitive impairment (P
      <.001 for all). CONCLUSION: We found an increased rate of self-reported cognitive
      impairment in older adults of 5 major racial/ethnic groups from 1997 through 2015
      in the United States. However, the rate of self-reported cognitive impairment was
      low, which may suggest underreporting. There is a need to further promote
      awareness of the disease among individuals, family members, and health care
      providers.

PMID- 29324218
TI  - Hours Lost to Planned and Unplanned Dental Visits Among US Adults.
AB  - INTRODUCTION: Poor oral health is associated with lost hours at work or school,
      which may affect a person's productivity. The objective of our study was to
      estimate work or school hours lost to dental visits among adults aged 18 and
      older by the types of visits (emergency or unplanned; routine, planned, or
      orthodontic; or cosmetic) and to determine the factors associated with hours
      lost. METHODS: We used the most recent Oral Health Supplement data, from the 2008
      National Health Interview Survey (NHIS), to estimate the total hours lost at work
      or school for dental visits among adults in the United States. The associations
      of the hours lost in unplanned and planned dental visits with socioeconomic
      characteristics, oral health status, and affordability were calculated. We used
      chi2 tests and logistic regression to determine associations at P < .05. RESULTS:
      An average of 320.8 million work or school hours were lost annually for dental
      care in the United States, of which 92.4 million hours were for emergency
      (unplanned) care (0.99 h/adult), 159.8 million for routine (planned) care or
      orthodontic care (1.71 h/adult), and 68.6 million for cosmetic care (0.73
      h/adult). Adults with poor oral health were more likely to lose one or more hours
      in unplanned dental visits (OR = 5.60; 95% confidence interval [CI], 3.25-9.63)
      than those who reported very good oral health. Not being able to afford dental
      care was positively associated with more work hours lost in unplanned care (odds
      ratio [OR] = 2.56; 95% CI, 1.76-3.73). Compared with Hispanic adults, non
      Hispanic white adults (OR = 2.09; 95% CI, 1.40-3.11) and non-Hispanic Asian
      adults and adults of other races/ethnicities (OR =1.91; 95% CI, 1.06-3.47) were
      more likely to lose any hours for planned care. Consistently, those with more
      than a high school education were more likely to lose any hours in planned care
      (OR = 1.39; 95% CI, 1.06-1.83) than those with a high school education or less.
      CONCLUSIONS: Dental problems result in hours lost from work and may adversely
      affect a person's productivity. There is disparity in lost hours at work by
      race/ethnicity and dental care affordability.

PMID- 29324217
TI  - Individual-Level Fitness and Absenteeism in New York City Middle School Youths,
      2006-2013.
AB  - INTRODUCTION: Youth health-related fitness positively affects academic outcomes,
      although limited research has focused on the relationship between fitness and
      school absenteeism. We examined the longitudinal association between individual
      children's fitness and lagged school absenteeism over 4 years in urban middle
      schools. METHODS: Six cohorts of New York City public school students were
      followed from grades 5 through 8 (school years 2006-2007 through 2012-2013; n =
      349,381). A 3-level longitudinal generalized linear mixed model was used to test
      the association of change in fitness composite percentile scores and 1-year
      lagged child-specific days absent. RESULTS: Adjusted 3-level negative binomial
      models showed that students with a more than 20% increase, 10% to 20% increase,
      less than 10% increase or decrease, and 10% to 20% decrease in fitness from the
      year prior had 11.9% (95% confidence interval [CI], 7.2-16.8), 6.1% (95% CI, 1.0
      11.4), 2.6% (95% CI, -1.1 to 6.5), and 0.4% (95% CI, -4.3 to 5.4) lower
      absenteeism compared with students with a more than 20% fitness decrease.
      CONCLUSION: Cumulative effects of fitness improvement could have a significant
      impact on child absenteeism over time, particularly in high-need subgroups.
      Future research should examine the potential for school-based fitness
      interventions to reduce absenteeism rates, particularly for youths who have
      fitness drop-offs in adolescence.

PMID- 29324219
TI  - Changing the Stage, Grade and Histological Subtypes of Renal Cell Carcinomas
      during 10 Years Period.
AB  - Renal cell carcinomas (RCCs) account 80-85% of all primary renal neoplasms and
      originate from the renal cortex. The patients who underwent radical or partial
      nephrectomy for renal tumour in our unit between January 2005 and 2015 were
      evaluated retrospectively. The patients were divided into two groups; group 1
      includes patients who were treated between January 2005 and December 2009, group
      2 those from January 2010 to 2015. There were 103 patients in group 1. The
      patients were between 21 and 89 years with mean age of 61.46 year. Renal cell
      carcinomas account 83.4% of the patients, benign renal tumours were 8.7% and
      transitional cell carcinomas were 7.7% of the patients in group 1. A total of
      32.5% RCCs were classified as pT1a, 24.4% as pT1b, 15.1% as pT2a, 11.6% as pT2b,
      15.1% as pT3a and 1.1% as pT4. There were 202 patients in group 2 and the
      patients were between 27 and 81 years with mean age of 58.5 year. Renal cell
      carcinomas comprised the main bulk of the tumours with 182 nephrectomy specimens.
      According to the pathological classification of RCCs, 51 specimens were found as
      pT1a, 54 were pT1b, 13 were pT2a, 14 were pT2b, 48 were pT3a and 2 were pT4.
      Although, the incidence of small renal masses has been increasing with widespread
      use of imaging techniques and recent advancements, the proportion of high grade
      and advanced stage renal tumours increased during the study period.

PMID- 29324220
TI  - 5-fluorouracil Toxicity Mechanism Determination in Human Keratinocytes: in vitro
      Study on HaCaT Cell Line.
AB  - 5-fluorouracil (5-FU) and capecitabine therapy is often accompanied by palmar
      plantar erythrodysesthesia (PPE) which is manifestation of 5-FU toxicity in
      keratinocytes. The main mechanisms of 5-FU action are thymidylate synthase (TS)
      inhibition which can be abrogated by thymidine and strengthened by
      calciumfolinate (CF) and incorporation of fluorouridinetriphosphate into RNA
      which can be abrogated by uridine. For proper PPE treatment 5-FU mechanism of
      action in keratinocytes needs to be elucidated. We used the 5-FU toxicity
      modulators uridine, thymidine and CF to discover the mechanism of 5-FU action in
      human keratinocyte cell line HaCaT. To measure the cellular viability, we used
      MTT test and RTCA test. CF did not augment 5-FU toxicity and 5-FU toxicity was
      weakened by uridine. Therefore, the primary mechanism of 5-FU toxicity in
      keratinocytes is 5-FU incorporation into RNA. The uridine protective effect
      cannot fully develop in the presence of CF. Thymidine addition to 5-FU and
      uridine treated cells not only prevents the toxicity-augmenting CF effect but it
      also prolongs the 5-FU treated cells survival in comparison to uridine only.
      Therefore, it can be assumed that in the presence of uridine the 5-FU toxicity
      mechanism is switched from RNA incorporation to TS inhibition. Although
      particular 5-FU toxicity mechanisms were previously described in various cell
      types, this is the first time when various combinations of pyrimidine nucleosides
      and CF were used for 5-FU toxicity mechanism elucidation in human keratinocytes.
      We suggest that for PPE treatment ointment containing uridine and thymidine
      should be further clinically tested.

PMID- 29324221
TI  - Catastrophic Left Ventricular Thrombosis Complicating Extra-corporeal Membrane
      Oxygenation: A Case Report.
AB  - A massive left ventricular thrombosis represents a rare however, catastrophic
      complication of a central veno-arterial extra-corporeal membrane oxygenation. We
      report a case of such complication in a patient with severe left ventricular
      dysfunction after cardiac surgery. Its management and preventive measures are
      described and discussed.

PMID- 29324222
TI  - Acquired Amegakaryocytic Thrombocytopenic Purpura Progressing into Aplastic
      Anemia.
AB  - Acquired amegakaryocytic thrombocytopenic purpura (AATP) is a rare hematological
      disorder characterized by severe thrombocytopenia and a complete or near-to
      complete absence of megakaryocytes in the bone marrow, while granulopoiesis, as
      well as erythropoiesis are usually preserved. Although autoimmune mechanisms are
      believed to be causative, the exact underlying pathogenesis is not known. To
      date, only few cases have been reported and management of this disease remains
      controversial with immunosuppression being the treatment modality of choice in
      the majority of patients. In this article, we report a case of newly acquired
      AATP without an associated autoimmune disease, refractory to corticoids,
      intravenous immunoglobulin (IVIG) and second-generation TPO (thrombopoietin)
      agonists, which have recently been approved for the treatment of
      thrombocytopenia. Finally, in accordance with other reports, disease progression
      into aplastic anemia has occurred.

PMID- 29324223
TI  - Navigating the Microbiota Seas: Triangulation Finds a Way Forward.
AB  - Identifying members of the intestinal microbiota that play causal roles in
      shaping human disease susceptibility has been an ongoing challenge. In their
      recent paper in Nature, Surana and Kasper (2017) present a new strategy that may
      help "triangulate" causal and therapeutically useful bacteria from the human gut.

PMID- 29324224
TI  - Good Bug, Bad Bug: Breaking through Microbial Stereotypes.
AB  - Our expanding knowledge of microbial mechanisms is challenging the notion of
      "good" versus "bad" microbes and encouraging a better understanding of their
      roles in various contexts before their widespread therapeutic and clinical
      application. The intestinal microbe Akkermansia muciniphila, a promising
      probiotic with an emerging cautionary tale, best highlights this challenge.

PMID- 29324226
TI  - Human-Specific Adaptations in Vpu Conferring Anti-tetherin Activity Are Critical
      for Efficient Early HIV-1 Replication In Vivo.
AB  - The HIV-1-encoded accessory protein Vpu exerts several immunomodulatory
      functions, including counteraction of the host restriction factor tetherin,
      downmodulation of CD4, and inhibition of NF-kappaB activity to facilitate HIV-1
      infection. However, the relative contribution of individual Vpu functions to HIV
      1 infection in vivo remained unclear. Here, we used a humanized mouse model and
      HIV-1 strains with selective mutations in vpu to demonstrate that the anti
      tetherin activity of Vpu is a prerequisite for efficient viral spread during the
      early phase of infection. Mathematical modeling and gain-of-function mutations in
      SIVcpz, the simian precursor of pandemic HIV-1, corroborate this finding.
      Blockage of interferon signaling combined with transcriptome analyses revealed
      that basal tetherin levels are sufficient to control viral replication. These
      results establish tetherin as a key effector of the intrinsic immune defense
      against HIV-1, and they demonstrate that Vpu-mediated tetherin antagonism is
      critical for efficient viral spread during the initial phase of HIV-1
      replication.

PMID- 29324225
TI  - The Marburgvirus-Neutralizing Human Monoclonal Antibody MR191 Targets a Conserved
      Site to Block Virus Receptor Binding.
AB  - Since their first identification 50 years ago, marburgviruses have emerged
      several times, with 83%-90% lethality in the largest outbreaks. Although no
      vaccines or therapeutics are available for human use, the human antibody MR191
      provides complete protection in non-human primates when delivered several days
      after inoculation of a lethal marburgvirus dose. The detailed neutralization
      mechanism of MR191 remains outstanding. Here we present a 3.2 A crystal structure
      of MR191 complexed with a trimeric marburgvirus surface glycoprotein (GP). MR191
      neutralizes by occupying the conserved receptor-binding site and competing with
      the host receptor Niemann-Pick C1. The structure illuminates previously
      disordered regions of GP including the stalk, fusion loop, CX6CC switch, and an N
      terminal region of GP2 that wraps about the outside of GP1 to anchor a
      marburgvirus-specific "wing" antibody epitope. Virus escape mutations mapped far
      outside the MR191 receptor-binding site footprint suggest a role for these other
      regions in the GP quaternary structure.

PMID- 29324228
TI  - LACTATEing Salmonella: A Host-Derived Fermentation Product Fuels Pathogen Growth.
AB  - Infection by Salmonella enterica serovar Typhimurium is accompanied by dysbiosis
      and a decrease of microbiota-derived butyrate. In this issue of Cell Host &
      Microbe, Gillis et al. (2018) demonstrate that the lack of butyrate reprograms
      colonic epithelial metabolism toward lactate fermentation. Lactate is then used
      as a respiratory electron donor, supporting Salmonella growth and thus promoting
      infection.

PMID- 29324229
TI  - Enteric Viruses Hitch a Ride on the Evolutionary Highway.
AB  - RNA viruses can recombine their genetic material during co-infection. However,
      the in vivo frequency of co-infections is unclear. In this issue of Cell Host &
      Microbe, Erickson et al. (2018) demonstrate that an enteric RNA virus
      concentrates itself through multi-virion binding to bacteria, thus increasing
      genetic recombination and virus adaptability.

PMID- 29324230
TI  - Neutrophils Cause an Intravascular Traffic Jam.
AB  - Neutrophil swarming is defined by large numbers of cells simultaneously and
      rapidly migrating to a site of injury or infection. In this issue of Cell Host &
      Microbe, Lee et al. (2018) demonstrate that intravascular swarming of neutrophils
      occurs in response to Candida albicans infection and causes vascular occlusion
      and pathological sequelae.

PMID- 29324227
TI  - Getting the "Kill" into "Shock and Kill": Strategies to Eliminate Latent HIV.
AB  - Despite the success of antiretroviral therapy (ART), there is currently no HIV
      cure and treatment is life long. HIV persists during ART due to long-lived and
      proliferating latently infected CD4+ T cells. One strategy to eliminate latency
      is to activate virus production using latency reversing agents (LRAs) with the
      goal of triggering cell death through virus-induced cytolysis or immune-mediated
      clearance. However, multiple studies have demonstrated that activation of viral
      transcription alone is insufficient to induce cell death and some LRAs may
      counteract cell death by promoting cell survival. Here, we review new approaches
      to induce death of latently infected cells through apoptosis and inhibition of
      pathways critical for cell survival, which are often hijacked by HIV proteins.
      Given advances in the commercial development of compounds that induce apoptosis
      in cancer chemotherapy, these agents could move rapidly into clinical trials,
      either alone or in combination with LRAs, to eliminate latent HIV infection.

PMID- 29324232
TI  - Insect Gut Microbiota: Accessories to the Bite.
AB  - The Leishmania parasite is transmitted via the bite of a sand fly. In this issue
      of Cell Host & Microbe, Dey et al. (2018) report that sand fly gut microbiota are
      also transferred to the bite site, promoting neutrophil recruitment and parasite
      dissemination to distal organs.

PMID- 29324231
TI  - Decoding a Salmonella Typhi Regulatory Network that Controls Typhoid Toxin
      Expression within Human Cells.
AB  - Salmonella Typhi is the cause of typhoid fever, a major global health concern. An
      essential virulence factor of this pathogen is typhoid toxin. In contrast to most
      AB-type toxins, typhoid toxin is exclusively expressed by intracellular bacteria.
      The regulatory networks that ensure this unique gene expression pattern are
      unknown. Here, we developed FAST-INSeq, a genome-wide screening approach to
      identify S. Typhi genes required for typhoid toxin expression within infected
      cells. We find that typhoid toxin expression is controlled by a silencing and
      counter-silencing mechanism through the opposing actions of the PhoP/PhoQ two
      component regulatory system and the histone-like protein H-NS. The screen also
      identified bacterial mutants that alter the proportion of intracellular S. Typhi
      that reside within an intravacuolar environment, which was essential for toxin
      expression. Collectively, these data describe a regulatory mechanism that allows
      a bacterial pathogen to exclusively express a virulence factor when located
      within a specific intracellular compartment.

PMID- 29324233
TI  - BCG Vaccination Protects against Experimental Viral Infection in Humans through
      the Induction of Cytokines Associated with Trained Immunity.
AB  - The tuberculosis vaccine bacillus Calmette-Guerin (BCG) has heterologous
      beneficial effects against non-related infections. The basis of these effects has
      been poorly explored in humans. In a randomized placebo-controlled human
      challenge study, we found that BCG vaccination induced genome-wide epigenetic
      reprograming of monocytes and protected against experimental infection with an
      attenuated yellow fever virus vaccine strain. Epigenetic reprogramming was
      accompanied by functional changes indicative of trained immunity. Reduction of
      viremia was highly correlated with the upregulation of IL-1beta, a heterologous
      cytokine associated with the induction of trained immunity, but not with the
      specific IFNgamma response. The importance of IL-1beta for the induction of
      trained immunity was validated through genetic, epigenetic, and immunological
      studies. In conclusion, BCG induces epigenetic reprogramming in human monocytes
      in vivo, followed by functional reprogramming and protection against non-related
      viral infections, with a key role for IL-1beta as a mediator of trained immunity
      responses.

PMID- 29324234
TI  - Sphingosine-1-phosphate mediates the therapeutic effects of bone marrow
      mesenchymal stem cell-derived microvesicles on articular cartilage defect.
AB  - Microvesicles (MVs) are emerging as a new mechanism of intercellular
      communication by transferring cellular components to target cells, yet their
      function in disease is just being explored. However, the therapeutic effects of
      MVs in cartilage injury and degeneration remain unknown. We found MVs contained
      high levels of sphingosine-1-phosphate (S1P) compared with the original bone
      marrow mesenchymal stem cells (MSCs). The enrichment of S1P in MVs was mediated
      by sphingosine kinase 1 (SphK1), but not by sphingosine kinase 2 (SphK2). Co
      culture of human chondrocytes with MVs resulted in increased proliferation of
      chondrocytes in vitro, which was mediated by activation of S1P receptor 1 (S1PR1)
      expressed on chondrocytes. Meanwhile, MVs inhibited interleukin 1 beta-induced
      human chondrocytes apoptosis in a dose dependent manner. Furthermore, uptake of
      MVs by primary cultures of human chondrocytes was mediated by CD44 expressed by
      MVs. Anti-CD44 antibody significantly reduced the uptake of fluorescent protein
      labeled MVs by chondrocytes. Further, blocking S1P by its neutralizing antibody
      significantly inhibited the therapeutic effects of MVs in vivo. Taken together,
      MVs showed therapeutic potential for treatment of clinical cartilage injury. This
      therapeutic potential is due to CD44-mediated uptake of MVs by chondrocytes and
      the S1P/S1PR1 axis-mediated proliferative effects of MVs on chondrocytes.

PMID- 29324235
TI  - A biphasic effect of cross-modal priming on visual shape recognition.
AB  - We used a cross-modal priming paradigm to evoke a biphasic effect in visual short
      term memory. Participants were required to match the memorandum (a visual shape,
      either spiky or curvy) to a delayed probe (a shape belonging to the same
      category). In two-thirds of trials the sequence of shapes was accompanied by a
      task-irrelevant sound (either tzk or upo, cross-modally correspondent to spiky
      and curvy shape categories, respectively). The biphasic effect occurred when a
      congruent vs. incongruent sound was presented 200ms after the memorandum, while
      it did not occur when the sound was presented 200ms before or simultaneously with
      it. The biphasic pattern of recognition sensitivities was revealed by an
      interaction between cross-modal congruency and probe delay, such that sensitivity
      was higher for visual shapes paired with a congruent rather than incongruent
      sound with a 300-ms delay, while the opposite was true with a 1300-ms delay. We
      suggest that this biphasic pattern of recognition sensitivities was dependent on
      the task-irrelevant sound activating different levels of shape processing as a
      function of the relative timing of sound, memorandum, and probe.

PMID- 29324236
TI  - IRF1 up-regulates isg15 gene expression in dsRNA stimulation or CSFV infection by
      targeting nucleotides -487 to -325 in the 5' flanking region.
AB  - Interferon (IFN)-stimulated gene 15 (ISG15) encodes a ubiquitin-like protein that
      is heavily involved in immune response elicitation. As an important member of
      interferon regulatory factor (IRF) family, IRF1 can activate the expression of
      multiple genes, including the human optineurin gene (Sudhakar et al., 2013). In
      this study, a sequence in the promoter region of the optineurin gene was compared
      to the 5' flanking region of the porcine isg15 gene. Porcine IRF1 also possesses
      antiviral activity against several swine viruses (Li et al., 2015), but the
      mechanism is not well understood. Herein, we report that porcine IRF1 and ISG15
      were up-regulated in porcine kidney (PK-15) cells following stimulation with
      double-stranded RNA (dsRNA) or classical swine fever virus (CSFV) infection. We
      also found that siRNA-mediated knockdown of IRF1 expression resulted in lower
      ISG15 expression in response to polyinosinic:polycytidylic acid [poly(I:C)] or
      CSFV infection. The overexpression of IRF1 resulted in ISG15 up-regulation. IRF1
      was shown to translocate to the nucleus in response to dsRNA stimulation. To
      further identify the functional domain of the isg15 gene that promotes IRF1
      transcriptional activity, firefly luciferase and ISG15 reporter systems were
      constructed. The results of the firefly luciferase and ISG15 reporter assay
      suggested that IRF1 mediates the up-regulation of ISG15. Nucleotides -487 to 
      325, located in the 5' flanking region of the isg15 gene, constituted the
      promoter region of IRF1. ChIP assay indicated that IRF1 protein was able to
      interact with the DNA in the 5'fr of isg15 gene in cells. As an innate immune
      response protein with broad-spectrum antiviral activity, the up-regulation of
      ISG15 mediated by IRF1 in porcine cells is reported for the first time. These
      results warrant further investigation into the antiviral activity of porcine IRF1
      against reported swine viruses.

PMID- 29324237
TI  - DNA induction of MDM2 promotes proliferation of human renal mesangial cells and
      alters peripheral B cells subsets in pediatric systemic lupus erythematosus.
AB  - The study is aimed to investigate the role of MDM2 in the pathogenesis of lupus
      nephritis (LN) in pediatric SLE (pSLE). We confirmed that MDM2 expression was
      increased in peripheral blood mononuclear cells (PBMCs) as well as renal specimen
      of SLE compared with that of controls by western blot and immunofluorescence
      staining. Percentage of apoptotic and necrotic CD4+T, CD8+T and B cells were
      detected by flow cytometry respectively and levels of plasma cell free DNA
      (cfDNA) were quantified in SLE and healthy controls (HC). We also proved that
      elevated apoptotic and necrotic CD4+T cells were the main cause for increased
      plasma levels of cfDNA in pSLE. Additionally, upon DNA transfection MDM2
      increased while P53 and P21 decreased in human renal mesangial cells (HRMC), with
      concomitant increase in proliferation rate and proportion of cells in S phase, as
      demonstrated by cell proliferation assay and cell cycle analysis. However, MDM2
      inhibition reversed the trend. Furthermore, percentage of switched memory B cells
      decreased and proportion of double negative B cells increased upon blockage of
      MDM2 in PBMC. In summary, our study provided the first evidence that DNA
      induction of MDM2 promotes proliferation of HRMC and alters peripheral B cells
      subsets in pSLE. Thus our study has not only elucidated the pathogenesis of MDM2
      in pediatric LN but also provided a novel target for drug development. In
      conclusion, our data suggested that apoptosis, cfDNA and MDM2 could form a
      pathological axis in SLE, especially in pSLE.

PMID- 29324238
TI  - Immunization with recombinant FliD confers protection against Helicobacter pylori
      infection in mice.
AB  - Nearly half of the world's population is infected with Helicobacter pylori.
      Clinical manifestations of this infection range from gastritis and peptic ulcers
      to gastric adenocarcinoma and lymphoma. Due to the emerging of antibiotic
      resistant strains and poor patient compliance of the antibiotic therapy, there is
      increasing interest in the development of a protective vaccine against H. pylori
      infection. The bacterial protein FliD forms a capping structure on the end of
      each flagellum which is critical to prevent depolymerization and structural
      degradation. In this study, the potential of FliD as a prospective H. pylori
      subunit vaccine was assessed. For this purpose, immunogenicity and protective
      efficacy of recombinant FliD (rFliD) from H. pylori was evaluated in C57BL/6
      mice. Purified rFliD was formulated with different adjuvants and administered via
      subcutaneous or oral route. Subcutaneous immunization with rFliD elicited
      predominantly mixed Th1 and Th17 immune responses, with high titers of specific
      IgG1 and IgG2a. Splenocytes of immunized mice exhibited strong antigen-specific
      memory responses, resulting in the secretion of high amounts of IFN-gamma and IL
      17, and low levels of IL-4. Immunization with rFliD caused a significant
      reduction in H. pylori bacterial load relative to naive control mice (p < 0.001),
      demonstrating a robust protective effect. Taken together, these results suggest
      that subcutaneous vaccination with rFliD formulated with CpG or Addavax could be
      considered as a potential candidate for the development of a subunit vaccine
      against H. pylori infection.

PMID- 29324240
TI  - Cognitive science in the era of artificial intelligence: A roadmap for reverse
      engineering the infant language-learner.
AB  - Spectacular progress in the information processing sciences (machine learning,
      wearable sensors) promises to revolutionize the study of cognitive development.
      Here, we analyse the conditions under which 'reverse engineering' language
      development, i.e., building an effective system that mimics infant's
      achievements, can contribute to our scientific understanding of early language
      development. We argue that, on the computational side, it is important to move
      from toy problems to the full complexity of the learning situation, and take as
      input as faithful reconstructions of the sensory signals available to infants as
      possible. On the data side, accessible but privacy-preserving repositories of
      home data have to be setup. On the psycholinguistic side, specific tests have to
      be constructed to benchmark humans and machines at different linguistic levels.
      We discuss the feasibility of this approach and present an overview of current
      results.

PMID- 29324239
TI  - How do glutathione antioxidant enzymes and total antioxidant status respond to
      air pollution exposure?
AB  - This study aims to investigate how antioxidant enzyme activity and overall
      antioxidant capacity respond to short-term changes in exposure to air pollution.
      201 participants were recruited before- and followed up during- and after- the
      2008 Beijing Olympics. Serum levels of antioxidant enzymes including glutathione
      S-transferases (GST), glutathione peroxidase (GPx), glutathione reductase (GR),
      and total antioxidant status (TAS) were measured. We used linear mixed-effects
      models to compare changes in antioxidant enzymes across the three periods after
      adjusting for potential confounding factors. Among all participants, glutathione
      peroxidase (GPx) levels decreased by 12.0% when air pollution dropped by 50-60%
      during the Olympics and increased by 6.5% when air pollution levels rose after
      the Olympics. The magnitude of increase among males, smokers, and older
      individuals was relatively smaller compared to females, nonsmokers, and younger
      individuals. Among all participants, total antioxidant status (TAS) significantly
      decreased by 6.23% during the games and continued to decrease by 4.41% after the
      games. However, among females, nonsmokers, and younger participants, there was an
      increase in TAS response to the elevated air pollution levels. Our study observed
      strong responses in GPx and TAS levels to the short-term decrease and increase of
      air pollution levels and responses varied among subgroups.

PMID- 29324241
TI  - Low-dimensional representation of cardiac motion using Barycentric Subspaces: A
      new group-wise paradigm for estimation, analysis, and reconstruction.
AB  - One major challenge when trying to build low-dimensional representation of the
      cardiac motion is its natural circular pattern during a cycle, therefore making
      the mean image a poor descriptor of the whole sequence. Therefore, traditional
      approaches for the analysis of the cardiac deformation use one specific frame of
      the sequence - the end-diastolic (ED) frame - as a reference to study the whole
      motion. Consequently, this methodology is biased by this empirical choice.
      Moreover, the ED image might be a poor reference when looking at large
      deformation for example at the end-systolic (ES) frame. In this paper, we propose
      a novel approach to study cardiac motion in 4D image sequences using low
      dimensional subspace analysis. Instead of building subspaces relying on a mean
      value we use a novel type of subspaces called Barycentric Subspaces which are
      implicitly defined as the weighted Karcher means of k+1 reference images instead
      of being defined with respect to one reference image. In the first part of this
      article, we introduce the methodological framework and the algorithms used to
      manipulate images within these new subspaces: how to compute the projection of a
      given image on the Barycentric Subspace with its coordinates, and the opposite
      operation of computing an image from a set of references and coordinates. Then we
      show how this framework can be applied to cardiac motion problems and lead to
      significant improvements over the single reference method. Firstly, by computing
      the low-dimensional representation of two populations we show that the parameters
      extracted correspond to relevant cardiac motion features leading to an efficient
      representation and discrimination of both groups. Secondly, in motion estimation,
      we use the projection on this low-dimensional subspace as an additional prior on
      the regularization in cardiac motion tracking, efficiently reducing the error of
      the registration between the ED and ES by almost 30%. We also derive a symmetric
      and transitive formulation of the registration that can be used both for frame-to
      frame and frame-to-reference registration. Finally, we look at the reconstruction
      of the images using our proposed low-dimensional representation and show that
      this multi-references method using Barycentric Subspaces performs better than
      traditional approaches based on a single reference.

PMID- 29324242
TI  - Expression profiling of the Dolichos lablab lectin during germination and
      development of the seed.
AB  - The temporal expression of the field bean (Dolichos lablab) galactose specific
      lectin, DLL-II, during germination, post-germination and seed development was
      evaluated using Native-PAGE followed by activity staining, immunodetection and
      quantitative Real Time PCR (qPCR). A rapid and steep decline in the polyphenol
      oxidase (PPO) and hemagglutinating activity during the initial stages of
      germination, which did not correlate with the slow decline in total protein was
      observed. During post germination period, PPO and hemagglutination activities
      were negligible, whereas a rapid resorption of the protein was evident. These
      results suggest that DLL-II is not a storage protein. The presence of mRNA in the
      quiescent seed and initial stages of germination are indicative of a very stable
      mRNA. DLL-II was expressed in high copies during seed development and increased
      dramatically between 10 and 20 days after flowering (DAF), suggesting a switch
      over stage in DLL-II expression. Transcript levels reached a maximum at the
      mature stage of seed development. Among the non-seed tissues examined, root
      showed the highest level. The high affinity binding to kinetin and indole acetic
      acid, the key hormones that regulate root development and its vascular
      differentiation add a new dimension to the physiological role of DLL-II in the
      seed. This finding, coupled with the PPO and hemagglutinating activity makes DLL
      II, truly a multifunctional protein.

PMID- 29324243
TI  - Using versus liking: Young children use ownership to predict actions but not to
      infer preferences.
AB  - Three experiments show that young children (N = 384) use ownership to predict
      actions but not to infer preferences. In Experiment 1, 3- to 6-year-olds
      considered ownership when predicting actions but did not expect it to trump
      preferences. In Experiment 2, 4- and 5-year-olds, but not 3-year-olds, used
      ownership to predict actions, and 5-year-olds grasped that an agent would use his
      or her own property despite preferring someone else's. This experiment also
      showed that relating an agent to an object interfered with 3- and 4-year-olds'
      judgments that a more attractive object is preferred. Finally, Experiment 3 found
      that 3- and 4-year-olds do not believe that owning an object increases regard for
      it. These findings are informative about the kinds of information children use to
      predict actions and the inferences they make from ownership. The findings also
      reveal specificity in how children use ownership to make judgments about others,
      and suggest that children more closely relate ownership to people's actions than
      to their desires.

PMID- 29324244
TI  - How social status influences our understanding of others' mental states.
AB  - The current study investigated whether children's relative social status within a
      context influences their ability to identify others' mental states. Across two
      experiments, 3- to 7-year-olds (N = 103) were randomly assigned to hold either an
      advantaged or disadvantaged social status and were assessed on their ability to
      accurately identify others' mental states (via false-belief and belief-emotion
      "theory of mind" assessments). When participants' status was manipulated by a
      structural factor (gender; Experiment 1), participants with disadvantaged status
      were more likely than participants with advantaged status to pass the false
      belief and belief-emotion assessments. When status was manipulated by an
      individual factor (performance; Experiment 2), participants with disadvantaged
      status were more likely to pass the false-belief assessment but not the belief
      emotion assessment. Results provide the first empirical evidence that an
      individual's contextualized perspective (i.e., his or her social status situated
      within a given context) influences the individual's ability to identify others'
      mental states.

PMID- 29324245
TI  - Heavy/light chain assay as a biomarker for diagnosis and follow-up of multiple
      myeloma.
AB  - BACKGROUND: The heavy-light chain (HLC) assay enables the accurate measurement of
      each isotype-specific heavy and light chain (i.e., IgGK, IgGlambda, IgAK, and
      IgAlambda) and the derivation of an HLC-pair ratio. However, to date, only
      limited data have validated the usefulness of serial HLC measurements in the
      routine follow-up of intact immunoglobulin multiple myeloma (MM) patients.
      METHODS: A total of 36 diagnostic and 671 post-treatment sera from 115 IgG and 61
      IgA MM patients were assessed with capillary zone electrophoresis,
      immunosubtraction electrophoresis, total immunoglobulin measurement, free light
      chain, and HLC assay. The correlations between M-protein levels and the HLC and
      FLC assay-derived parameters were examined and the clinical significance of the
      biomarkers was evaluated according to patients' status. RESULTS: Involved HLC
      (iHLC) was the best biomarker correlating with M-protein concentration in both
      IgG and IgA MM, and could provide a surrogate marker substituting M-protein
      levels to follow the course of the disease, especially in beta-migrating IgA M
      proteins. The distribution of iHLC values as well as HLC-pair ratios (rHLC)
      yielded significantly different results among the various response categories in
      both IgG and IgA MM. In addition, we detected 2 cases in which an abnormal rHLC
      in a stringent complete remission (sCR) sample was a marker of early non
      symptomatic relapse. CONCLUSION: In this study of a cohort of 176 patients in a
      routine clinical setting, we have provided evidence of the clinical utility of
      real world HLC assays for the identification of M-proteins and to monitor M
      proteins with an emphasis on IgA monoclonal gammopathies.

PMID- 29324246
TI  - Spin-echo based diagonal peak suppression in solid-state MAS NMR homonuclear
      chemical shift correlation spectra.
AB  - The feasibility of using the spin-echo based diagonal peak suppression method in
      solid-state MAS NMR homonuclear chemical shift correlation experiments is
      demonstrated. A complete phase cycling is designed in such a way that in the
      indirect dimension only the spin diffused signals are evolved, while all signals
      not involved in polarization transfer are refocused for cancellation. A data
      processing procedure is further introduced to reconstruct this acquired spectrum
      into a conventional two-dimensional homonuclear chemical shift correlation
      spectrum. A uniformly 13C, 15N labeled Fmoc-valine sample and the transmembrane
      domain of a human protein, LR11 (sorLA), in native Escherichia coli membranes
      have been used to illustrate the capability of the proposed method in comparison
      with standard 13C-13C chemical shift correlation experiments.

PMID- 29324247
TI  - mGlu5-dependent modulation of anxiety during early withdrawal from binge-drinking
      in adult and adolescent male mice.
AB  - Binge alcohol-drinking elicits symptoms of negative affect such as anxiety upon
      cessation, which is a source of negative reinforcement for perpetuating this
      pattern of alcohol abuse. Binge-induced anxiety during early (24 h) withdrawal is
      associated with increased expression of metabotropic glutamate receptor 5 (mGlu5)
      within the nucleus accumbens shell (AcbSh) of adult male mice, but was unchanged
      in anxiety-resilient adolescents. Herein, we determined the role of mGlu5
      signaling in withdrawal-induced anxiety via pharmacological manipulation using
      the mGlu5 negative allosteric modulator MTEP and the positive allosteric
      modulator CDPPB. Adult (PND 56) and adolescent (PND 28) male C57BL/6J mice binge
      drank for 14 days under 3-bottle-choice procedures for 2 h/day; control animals
      drank water only. Approximately 24 h following the final alcohol presentation,
      animals were treated with 30 mg/kg IP MTEP, CDPPB, or vehicle and then tested,
      thirty minutes later, for behavioral signs of anxiety. Vehicle-treated binge
      drinking adults exhibited hyperanxiety in all paradigms, while vehicle-treated
      binge-drinking adolescents did not exhibit withdrawal-induced anxiety. In adults,
      30 mg/kg MTEP decreased alcohol-induced anxiety across paradigms, while 3 mg/kg
      MTEP was anxiolytic in adult water controls. CDPPB was modestly anxiogenic in
      both alcohol- and water-drinking mice. Adolescent animals showed minimal response
      to either CDPPB or MTEP, suggesting that anxiety in adolescence may be mGlu5
      independent. These results demonstrate a causal role for mGlu5 in withdrawal
      induced anxiety in adults and suggest age-related differences in the behavioral
      pharmacology of the negative reinforcing properties of alcohol.

PMID- 29324249
TI  - Disability in progressive MS is associated with T2 lesion changes.
AB  - BACKGROUND: Progressive multiple sclerosis (MS) is characterised by diffuse
      changes on brain magnetic resonance imaging (MRI), which complicates the use of
      MRI as a diagnostic and prognostic marker. The relationship between MRI measures
      (conventional and non-conventional) and clinical disability in progressive MS
      therefore warrants further investigation. OBJECTIVE: To investigate the
      relationship between clinical disability and MRI measures in patients with
      progressive MS. METHODS: Data from 93 primary and secondary progressive MS
      patients who had participated in 3 phase 2 clinical trials were included in this
      cross-sectional study. From 3T MRI baseline scans we calculated total T2 lesion
      volume and analysed magnetisation transfer ratio (MTR) and the diffusion tensor
      imaging indices fractional anisotropy (FA) and mean diffusivity (MD) in T2
      lesions, normal-appearing white matter (NAWM) and cortical grey matter.
      Disability was assessed by the Expanded Disability Status Scale (EDSS) and the MS
      functional composite. RESULTS: T2 lesion volume was associated with impairment by
      all clinical measures. MD and MTR in T2 lesions were significantly related to
      disability, and lower FA values correlated with worse hand function in NAWM. In
      multivariable analyses, increasing clinical disability was independently
      correlated with increasing T2 lesion volumes and MTR in T2 lesions. CONCLUSION:
      In progressive MS, clinical disability is related to lesion volume and
      microstructure.

PMID- 29324248
TI  - Varenicline for tobacco-dependence treatment in alcohol-dependent smokers: A
      randomized controlled trial.
AB  - BACKGROUND: Tobacco use is prevalent among persons with alcohol abuse and
      dependence. Varenicline has been shown to be the most effective pharmacotherapy
      for smoking cessation and may decrease alcohol consumption. The purpose of this
      study was to evaluate the efficacy of 12 weeks of varenicline for increasing
      smoking abstinence rates in smokers with alcohol abuse or dependence. METHODS:
      Participants were eligible for enrollment if they were 18 years or older, smoked
      10 or more cigarettes per day for at least 6 months, had current alcohol abuse or
      dependence, and were interested in quitting smoking. Participants were randomly
      assigned to receive 12 weeks of varenicline 1 mg twice daily or matching placebo.
      The primary end point was 7-day point prevalence smoking abstinence at week 12.
      RESULTS: The 7-day point prevalence smoking abstinence rate at 12 weeks was
      significantly higher with varenicline (n = 16) than placebo (n = 17) (43.8% vs
      5.9%; P = .01). At 24 weeks, the 7-day point prevalence smoking abstinence rate
      was still significantly higher with varenicline than placebo (31.3% vs 0%; P =
      .02). At 12 weeks, mean (SD) drinks per drinking day was significantly lower with
      varenicline than placebo (5.7 [3.9] vs 9.0 [5.3] drinks; treatment effect
      estimate, -2.8 [90% CI, -6.6 to -1.0]). Adverse events were minor and comparable
      to varenicline clinical trials. CONCLUSIONS: Varenicline is safe and efficacious
      for increasing smoking abstinence rates in smokers with alcohol abuse or
      dependence. Varenicline may decrease alcohol consumption in this population of
      smokers.

PMID- 29324250
TI  - Novel sulfonamide incorporating piperazine, aminoalcohol and 1,3,5-triazine
      structural motifs with carbonic anhydrase I, II and IX inhibitory action.
AB  - A new series of s-triazine derivatives incorporating sulfanilamide,
      homosulfanilamide, 4-aminoethyl-benzenesulfonamide and piperazine or aminoalcohol
      structural motifs is reported. Molecular docking was exploited to select
      compounds from virtual combinatorial library for synthesis and subsequent
      biological evaluation. The compounds were prepared by using step by step
      nucleophilic substitution of chlorine atoms from cyanuric chloride (2,4,6
      trichloro-1,3,5-triazine). The compounds were tested as inhibitors of
      physiologically relevant carbonic anhydrase (CA, EC 4.2.1.1) isoforms.
      Specifically, against the cytosolic hCA I, II and tumor-associated hCA IX. These
      compounds show appreciable inhibition. hCA I was inhibited with KIs in the range
      of 8.5-2679.1 nM, hCA II with KIs in the range of 4.8-380.5 nM and hCA IX with
      KIs in the range of 0.4-307.7 nM. As other similar derivatives, some of the
      compounds showed good or excellent selectivity ratios for inhibiting hCA IX over
      hCA II, of 3.5-18.5. 4-[({4-Chloro-6-[(4-hydroxyphenyl)amino]-1,3,5-triazin-2
      yl}amino)methyl] benzene sulfonamide demonstrated subnanomolar affinity for hCA
      IX (0.4 nM) and selectivity (18.50) over the cytosolic isoforms. This series of
      compounds may be of interest for the development of new, unconventional
      anticancer drugs targeting hypoxia-induced CA isoforms such as CA IX.

PMID- 29324252
TI  - The genetic diversity and applicability assessment of autosomal STRs among
      Chinese populations by a novel Fixation Index and Nei's index.
AB  - The population-specific FST in STR loci of Chinese populations has not been
      focused on. Here, we genotyped 19 STRs in 530 unrelated healthy individuals of
      Xuzhou Han population, and collected data of 30,308 samples from 32 Hans and 50
      minorities nationwide. The population-specific betai and locus-specific betail
      were calculated to evaluate the applicable value of STRs. Next, we generated the
      genetic structure of various ethnic populations by Neighbor-Joining tree and
      Multidimensional Scaling plot based on pairwise Nei's distances. We found that
      TH01 and TPOX possessed high ability in discriminating populations which may be
      reled to the mutation rate of these STRs. Additionally, our data indicated that
      Chinese Han was homogenous and the population-specific betais of northern Hans
      were generally smaller than southern Hans (p > 0.05). We concluded that
      population-specific FST for autosomal STR loci could be used to reveal the unique
      genetic characteristics and thus uncover the genetic relationship among Chinese
      populations.

PMID- 29324251
TI  - Potential role of Plasmodium falciparum exported protein 1 in the chloroquine
      mode of action.
AB  - In the human malaria parasite Plasmodium falciparum, membrane glutathione S
      transferases (GST) have recently emerged as potential cellular detoxifying units
      and as drug target candidates with the artemisinin (ART) class of antimalarials
      inhibiting their activity at single-digit nanomolar potency when activated by
      iron sources such as cytotoxic hematin. Here we put forward the hypothesis that
      the membrane GST Plasmodium falciparum exported protein 1 (PfEXP1, PF3D7_1121600)
      might be directly involved in the mode of action of the unrelated antimalarial 4
      aminoquinoline drug chloroquine (CQ). Along this line we report potent
      biochemical inhibition of membrane glutathione S-transferase activity in
      recombinant PfEXP1 through CQ at half maximal inhibitory CQ concentrations of
      9.02 nM and 19.33 nM when using hematin and the iron deficient 1-chloro-2,4
      dinitrobenzene (CDNB) as substrate, respectively. Thus, in contrast to ART, CQ
      may not require activation through an iron source such as hematin for a potent
      inhibition of membrane GST activity. Arguably, these data represent the first
      instance of low nanomolar inhibition of an essential Plasmodium falciparum enzyme
      through a 4-aminoquinoline and might encourage further investigation of PfEXP1 as
      a potential CQ target candidate.

PMID- 29324253
TI  - A qualitative study comparing physician-reported barriers to treating addiction
      using buprenorphine and extended-release naltrexone in U.S. office-based
      practices.
AB  - AIM: Our aim was to compare physician-reported barriers to sublingual
      buprenorphine (BUP) and extended-release naltrexone (XR-NLT) prescribing in U.S.
      office-based practices, and to identify potential policies for minimizing these
      barriers. Only one previous qualitative study has examined physician-reported
      barriers to prescribing XR-NLT and no qualitative study has compared physician
      reported barriers between the two medications. METHODS: Researchers conducted
      individual semi-structured and in-depth interviews with 20 licensed physicians in
      four U.S. states between January 2016 and May 2017. Interview questions included
      general barriers to addiction treatment in office-based settings, barriers
      specific to BUP and XR-NLT prescribing, and potential government policies to
      decrease barriers. Researchers conducted thematic analysis of transcribed
      interviews. They developed and pilot tested a coding template based on a sample
      of transcripts, independently coded transcripts in Dedoose software, conducted
      consensus coding to eliminate coding discrepancies, and then assessed data for
      themes using research questions as a guide. RESULTS: General barriers to office
      based OUD treatment included limited physician education, limited insurance
      reimbursement, stigma, and perceptions of "difficult" patients. Barriers specific
      to BUP prescribing included regulatory restrictions, liability fears, and
      restrictions imposed by the criminal justice system. Barriers specific to XR-NLT
      prescribing included limited access to medically-supervised opioid
      detoxification, lack of awareness of the medication, and patient fears or
      disinterest. Participants without experience prescribing either medication
      emphasized barriers to treating OUD in general. Participants with experience
      prescribing BUP and/or XR-NLT described barriers to treating OUD in general as
      well as barriers specific to each medication. Policy makers should increase
      access to addiction medicine education, mandate insurance coverage of both
      medications and inpatient detoxification, prohibit excessive insurance prior
      authorization requirements, increase insurance reimbursement for behavioral
      healthcare, and incentivize interdisciplinary collaboration. CONCLUSIONS: While
      overlap exists, some barriers to BUP prescribing differ from barriers to XR-NLT
      prescribing.

PMID- 29324254
TI  - PRDM14 is expressed in germ cell tumors with constitutive overexpression altering
      human germline differentiation and proliferation.
AB  - Germ cell tumors (GCTs) are a heterogeneous group of tumors occurring in gonadal
      and extragonadal locations. GCTs are hypothesized to arise from primordial germ
      cells (PGCs), which fail to differentiate. One recently identified susceptibility
      loci for human GCT is PR (PRDI-BF1 and RIZ) domain proteins 14 (PRDM14). PRDM14
      is expressed in early primate PGCs and is repressed as PGCs differentiate. To
      examine PRDM14 in human GCTs we profiled human GCT cell lines and patient samples
      and discovered that PRDM14 is expressed in embryonal carcinoma cell lines,
      embryonal carcinomas, seminomas, intracranial germinomas and yolk sac tumors, but
      is not expressed in teratomas. To model constitutive overexpression in human
      PGCs, we generated PGC-like cells (PGCLCs) from human pluripotent stem cells
      (PSCs) and discovered that elevated expression of PRDM14 does not block early PGC
      formation. Instead, we show that elevated PRDM14 in PGCLCs causes proliferation
      and differentiation defects in the germline.

PMID- 29324255
TI  - Aberrant, autistic, and food-related behaviors in adults with Prader-Willi
      syndrome. The comparison between young adults and adults.
AB  - This study aims to explore the differences of age as well as genotype in regards
      to the severity of behavioral symptoms in Prader-Willi syndrome (PWS), with
      emphasis on the comparison between youngadults and adults.The Food Related
      Problem Questionnaire (FRPQ), the Aberrant Behavior Checklist Japanese Version
      (ABC-J), and the Pervasive Developmental Disorders Autism Society Japan Rating
      Scale (PARS) were administered to 46 PWS patients, including 33 young adults
      (ages 18-28) and 13 adults(ages 30-45). To examine the differences between young
      adults and adults, Mann-Whitney U tests were conducted. Statistically significant
      differences were found in ABC-J (p = .027) and PARS (p = .046), with higher
      scores in young adults than adults. Such differences between the two age groups
      were still true for the subgroups having a paternal chromosome 15q deletion (DEL)
      for ABC-J (p = .050) and part of PARS ("Problematic behavior"; p = .007). By
      contrast, there was no significant differences between young adults and adults
      regarding FRPQ (p = .65).These results suggest that aberrant behaviors decline
      from around the ages of thirty, in PWS patients in general and in DEL subgroups
      in particular, while food-related behaviors give no indication of diminishing in
      spite of developmental growth.

PMID- 29324256
TI  - DFT/TD-semiempirical study on the structural and electronic properties and
      absorption spectra of supramolecular fullerene-porphyrine-metalloporphyrine
      triads based dye-sensitized solar cells.
AB  - In the present work density functional theory (DFT) and time-dependent
      semiempirical ZNIDO/S (TD-ZNIDO/S) methods have been used to investigate the
      ground state geometries, electronic structures and excited state properties of
      triad systems. The influences of the type of metal in the porphyrin ring, change
      in bridge position and porphyrine-ZnP duplicate on the energies of frontier
      molecular orbital and UV-Vis spectra has been studied. Geometry optimization, the
      energy levels and electron density of the Highest Occupied Molecular Orbital
      (HOMO) and the Lowest Unoccupied Molecular Orbital (LUMO), chemical hardness
      (eta), electrophilicity index (omega), electron accepting power (omega+) were
      calculated using ZINDO/S method to predict which molecule is the most efficient
      with a great capability to be used as a triad molecule in solar industry.
      Moreover the light harvesting efficiency (LHE) was calculated by means of the
      oscillator strengths which are obtained by TD-ZINDO/S calculation. Theoretical
      studies of the electronic spectra by ZINDO/S method were helpful in interpreting
      the observed electronic transitions. This aspect was systematically explored in a
      series of C60-Porphyrine-Metalloporphyrine (C60-P-Mp) triad system with M being
      Fe, Co, Ni, Ti, and Zn. Generally, transition metal coordination compounds are
      used as effective sensitizers, due to their intense charge-transfer absorption
      over the whole visible range and highly efficient metal-to-ligand charge
      transfer. We aim to optimize the performance of the title solar cells by altering
      the frontier orbital energy gaps. The results reveal that cell efficiency can be
      enhanced by metal functionalization of the free base porphyrin. Ti-porphyrin was
      found to be the most efficient dye sensitizer for dye sensitized solar cells
      (DSSCs) based on C60-P-Mptriad system due to C60-Por-TiP complex has lower
      chemical hardness, gap energy and chemical potential as well as higher electron
      accepting power among other complexes. In addition, the performance of solar
      cells favors better with doubly and increasing the pi conjugated of the bridge.

PMID- 29324257
TI  - Effects of pelargonidin-3-O-glucoside and its metabolites on lipopolysaccharide
      stimulated cytokine production by THP-1 monocytes and macrophages.
AB  - Epidemiological evidence suggests cardioprotective effects of anthocyanin
      consumption. This study examined the predominant strawberry anthocyanin,
      pelargonidin-3-O-glucoside (Pg-3-glc), and three of its plasma metabolites
      (protocatechuic acid [PCA], 4-hydroxybenzoic acid, and phloroglucinaldehyde
      [PGA]) for effects on the production of selected cytokines by lipopolysaccharide
      stimulated THP-1 monocytes and macrophages. Concentrations of tumor necrosis
      factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-6, IL-8 and IL-10 were
      determined using a cytometric bead array kit. PCA at 0.31, 1.25 and 20 MUM and
      PGA at 5 and 20 MUM decreased the concentration of IL-6 in the monocyte cultures,
      but there were no effects on TNF-alpha, IL-1beta, IL-8 and IL-10 and there were
      no effects of the other compounds. In the macrophage cultures, PGA at 20 MUM
      decreased the concentrations of IL-6 and IL-10, but there was no effect on TNF
      alpha, IL-1beta and IL-8 and there were no effects of the other compounds. In
      conclusion, while the effects of PGA were only observed at the higher,
      supraphysiological concentration and are thus considered of limited physiological
      relevance overall, the anti-inflammatory properties of PCA were observed at both
      the lower, physiologically relevant, and the higher concentrations; however,
      effects were modest and limited to IL-6 and monocytes. These preliminary data
      suggest potential for physiologically attainable PCA concentrations to modulate
      IL-6 production by monocytes.

PMID- 29324258
TI  - IL-18 and Stem Cell Factor affect hematopoietic progenitor cells in HIV-infected
      patients treated during primary HIV infection.
AB  - The impact of early antiretroviral therapy (ART) during Primary HIV Infection
      (PHI) on the hematopoietic progenitor cells (HPCs) homeostasis is not available.
      This study aimed to characterize HPCs and their relationship with cytokines
      regulating progenitors function in ART-treated patients with PHI. We enrolled HIV
      infected patients treated with ART during PHI. Circulating HPCs, Lymphoid-HPCs (L
      HPCs) frequency and plasmatic concentrations of IL-7, IL-18 and Stem Cell Factor
      (SCF) were analysed at baseline and after 6 months of therapy. ART introduction
      during PHI restored the decline of L-HPCs, induced a decrease in the level of pro
      inflammatory IL-18 cytokine and a parallel increase of SCF. Moreover, L-HPCs
      frequency positively correlated with IL-18 at baseline, and with SCF after 6
      months of therapy, suggesting that different signals impact L-HPCs expansion and
      maintenance before and after treatment. Finally, the SCF receptor expression on
      HPCs decreased after early ART initiation. These insights may open new
      perspectives for the evaluation of cytokine-driven L-HPCs expansion and their
      impact on the homeostasis of hematopoietic compartment during HIV infection.

PMID- 29324260
TI  - Plasma leptin, but not resistin, TNF-alpha and adiponectin, is associated with
      echocardiographic parameters of cardiac remodeling in patients with coronary
      artery disease.
AB  - The aim of this research was to assess the relationship between plasma
      adiponectin, leptin, resistin, tumor necrosis factor alpha (TNF-alpha) levels and
      echocardiographic parameters of ventricular remodeling in patients with coronary
      artery disease, without acute myocardial infarction. The study population
      consisted of 49 patients with echocardiographic measurements performed. After
      adjustment for age, gender, body mass index, systolic and diastolic blood
      pressure, and glycaemia, adiponectin was statistically significant associated
      with interventricular septum thickness (beta = -0.304), left ventricular
      posterior wall thickness (beta = -0.402), left ventricular end diastolic diameter
      (LVEDD; beta = 0.385) and left ventricular relative wall thickness (beta = 
      0.448, p < .05 for all). The associations were no longer significant when only
      patients without diabetes were included in the analysis. Leptin was associated
      with LVEDD (beta = -0.354) and left ventricular relative wall thickness (beta =
      0.385, p < .05 for all). No associations between resistin, TNF-alpha and
      echocardiographic left ventricular parameters assessed were found in these
      patients. In conclusion, in patients with coronary artery disease and without
      acute myocardial infarction leptin may represent a potential mechanism of adverse
      cardiac remodeling. Resistin and TNF-alpha might not be involved in ventricular
      remodeling in these patients.

PMID- 29324259
TI  - Higher serum vitamin D levels are associated with protective serum cytokine
      profiles in patients with ulcerative colitis.
AB  - BACKGROUND & AIMS: Vitamin D has immune modulating effects on cytokines. Serum
      vitamin D levels are associated with the risk of relapse in patients with
      ulcerative colitis (UC), through unknown mechanisms. We tested the hypothesis
      that this beneficial role of vitamin D on UC is mediated through anti
      inflammatory serum cytokine profiles. METHODS: Serum samples from a prospective
      cohort of seventy UC patients in clinical remission were collected and baseline
      histological and endoscopic scores were recorded at enrollment. Clinical relapse
      events were recorded over the 12-month follow-up period. Serum vitamin D and
      cytokines levels (IL-6, IL-8, IL-17A, TNF-alpha, IFN-gamma, IL-4, IL-10) were
      quantified using ELISA. Linear regression was used to determine correlation
      between vitamin D and cytokine profiles. Logistic regression models were used to
      determine the association between serum cytokine profiles and baseline histologic
      mucosal healing and clinical relapse. RESULTS: Higher serum vitamin D levels
      positively correlated with higher ratios of IL-4 + IL-10/IL-17A + TNF-alpha (r =
      0.37, P < .01), and IL-4 + IL-10/IL-6 + TNF-alpha (r = 0.32, P < .01). In
      multivariate analysis, IL-4 + IL-10/IL-17A + TNF-alpha ratios at baseline were
      associated with the presence of histologic mucosal healing (O.R. 1.29, 95% CI
      1.02-1.62, P = .03). A higher ratio of serum IL-4 + IL-10 to IL-6 + TNF-alpha was
      associated with a reduced risk of clinical relapse (O.R. 0.72, 95% CI 0.58-0.89,
      P = .003), and longer time to relapse (p = .03), over the 12-month follow-up
      period. This ratio during remission had an AUC of 0.7 in predicting later
      clinical relapse. CONCLUSIONS: Vitamin D is associated with anti-inflammatory
      serum cytokine profiles. Anti-inflammatory cytokine patterns may mediate the
      protective effects of higher serum vitamin D levels in patients with ulcerative
      colitis.

PMID- 29324261
TI  - Platelet Toll-like receptor and its ligand HMGB-1 expression is increased in the
      left atrium of atrial fibrillation patients.
AB  - BACKGROUND: Atrial fibrillation(AF) is the most common sustained arrhythmia. Its
      most feared sequelae are stroke and peripheral thromboembolism due to atrial
      thrombi formation. Mechanisms underlying the relationship between platelet
      activation and left atrial thrombi have not been clearly elucidated yet. We aimed
      to investigate whether immune-mediated platelet activation occurred in AF
      patients in this cross-sectional study. METHODS: Persistent and paroxysmal AF
      patients who underwent cryoballoon-based AF ablation between March 2015 and July
      2016 were included as the patient group. Patients without AF in whom transseptal
      puncture was performed at the same period for purposes other than AF ablation
      were included as the control group. Peripheral and left atrial blood samples were
      obtained for determination of platelet Toll-like receptor(TLR)-2, TLR-4 and high
      mobility group box-1(HMGB-1) expression levels. RESULTS: A total of 75 subjects
      (53 patients with AF and 22 control subjects) [mean: 60.33 (SD: 6.14) years,
      57.33% male] were included. Left atrial and peripheral TLR-2, 4 and HMGB-1
      expression levels were significantly higher in the patient group when compared to
      the controls. Left atrial platelet TLR-2 and TLR-4 expression and serum HMGB-1
      levels were higher in persistent AF patients compared to paroxysmal AF patients.
      In the patient group, left atrial expression of TLR-2, 4 and HMGB-1 were
      significantly higher than the peripheral expression levels. CONCLUSION: Findings
      of our study suggest evidence for immune-mediated platelet activation in the left
      atria of AF patients.

PMID- 29324262
TI  - Altered regulatory cytokine profiles in cases of pediatric respiratory syncytial
      virus infection.
AB  - OBJECTIVES: Regulatory cytokines are associated with viral infection. The
      objective of this study was to evaluate the relation between serum regulatory
      cytokines concentrations and respiratory syncytial virus (RSV) disease. METHODS:
      We enrolled 325 children aged < 24 months who were diagnosed with acute
      respiratory tract infection. Twenty age-matched healthy children were enrolled as
      controls. Nasopharyngeal swabs were analyzed to identify virus by reverse
      transcription polymerase chain reaction, and blood samples were taken to quantify
      the regulatory cytokine concentrations, including interleukin (IL)-35, IL-10 and
      transforming growth factor (TGF)-beta1 using the Bio-Plex immunoassay or enzyme
      linked immunosorbent assay. RESULTS: RSV disease was associated with a great
      regulatory cytokine response than healthy children, among 89 RSV-infected
      patients, serum IL-35 (P = .0001) and IL-10 (P = .006) was significantly elevated
      in comparison with healthy controls. Young children (0< age <=6 months) with RSV
      infection had significantly lower IL-35 and IL-10 expression but needed more
      oxygen therapy and more severe disease comparing with older children (12< age <24
      months). Comparing with mild group, the expression levels of IL-10 were
      significantly lower in children with moderate and severe disease (P = .012 and P
      = .005, respectively). And levels of IL-10 was inversely associated with total
      duration of RSV infection symptoms (r = - 0.311, P = .019). CONCLUSION: Children
      with RSV infected had increased serum regulatory cytokine IL-10 and IL-35
      concentrations. Elevated expression of IL-10 and IL-35 were contributed to
      protect hypoxia and reduce the severity of disease.

PMID- 29324263
TI  - The role of pro-fibrotic biomarkers in paroxysmal and persistent atrial
      fibrillation.
AB  - PURPOSE: Signaling pathways involved in electrical, structural and contractile
      remodeling processes behind development and progression of atrial fibrillation
      (AF) have not been completely elucidated, but it seems to be related to complex
      interactions among neurohormonal and cellular mediators. We aimed to investigate
      interleukin-6 (IL-6), transforming growth factor-beta1 (TGF-beta1), matrix
      metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), as
      biomarkers of atrial remodeling, in patients with paroxysmal and persistent AF,
      and their correlation with N-terminal prohormone of brain natriuretic peptide (NT
      proBNP) and left atrial (LA) diameter. METHODS: Thirty-seven patients (22M/15F)
      with paroxysmal AF, 32 patients (22M/10F) with persistent AF and 30 healthy
      control subjects (18M/12F) were enrolled in the study. Serum levels of biomarkers
      were measured by ELISA. Cardiac function was assessed echocardiographically.
      RESULTS: IL-6 levels and MMP-9/TIMP-1 ratio were significantly higher in AF
      patients than in non-AF controls (P < .001), and in persistent than in paroxysmal
      AF (P < .001), in line with NT-proBNP and LA diameter. In contrast, TGF
      beta1levels declined with increasing AF duration (from 51.2 pg/mL, IQR: 38.9-87.9
      pg/mL in paroxysmal to 23.9 pg/mL, IQR: 16.9-43.6 pg/mL in persistent AF). TGF
      beta1 was negatively correlated with NT-proBNP (r = -0.53, P = .001 in paroxysmal
      AF and r = -0.71, P < .001 in persistent AF) and LA diameter (r = -0.44, P = .006
      in paroxysmal AF and r = -0.51, P = .003 in persistent AF). CONCLUSIONS: Our
      results demonstrate that AF development and progression (from paroxysmal to
      persistent) is associated with a gradual increase in serum levels of NT-proBNP,
      IL-6 and MMP-9/TIMP-1 ratio. Moreover, this study suggests that the relationship
      between TGF-beta1, NT-proBNP and LA diameter allows for the progression of atrial
      remodeling during AF, despite compensatory changes in the TGF-beta1 signaling
      pathway.

PMID- 29324264
TI  - Driver education: Enhancing knowledge of sleep, fatigue and risky behaviour to
      improve decision making in young drivers.
AB  - This study assessed the impact of an education program on knowledge of sleepiness
      and driving behaviour in young adult drivers and their performance and behaviour
      during simulated night driving. Thirty-four participants (18-26 years old) were
      randomized to receive either a four-week education program about sleep and
      driving or a control condition. A series of questionnaires were administered to
      assess knowledge of factors affecting sleep and driving before and after the four
      week education program. Participants also completed a two hour driving simulator
      task at 1am after 17 h of extended wakefulness to assess the impact on driving
      behaviour. There was an increase in circadian rhythm knowledge in the
      intervention group following the education program. Self-reported risky behaviour
      increased in the control group with no changes in other aspects of sleep
      knowledge. There were no significant differences in proportion of intervention
      and control participants who had microsleeps (p <= .096), stopped driving due to
      sleepiness (p = .107), recorded objective episodes of drowsiness (p = .455), and
      crashed (p = .761), although there was a trend towards more control participants
      having microsleeps and stopping driving. Those in the intervention group reported
      higher subjective sleepiness at the end of the drive [M = 6.25, SD = 3.83, t(31)
      = 2.15, p = .05] and were more likely to indicate that they would stop driving [M
      = 3.08, SD = 1.16, t(31) = 2.24, p = .04]. The education program improved some
      aspects of driver knowledge about sleep and safety. The results also suggested
      that the education program lead to an increased awareness of sleepiness.
      Education about sleep and driving could reduce the risk of drowsy driving and
      associated road trauma in young drivers, but requires evaluation in a broader
      sample with assessment of real world driving outcomes.

PMID- 29324265
TI  - Bayesian spatiotemporal crash frequency models with mixture components for space
      time interactions.
AB  - The traffic safety research has developed spatiotemporal models to explore the
      variations in the spatial pattern of crash risk over time. Many studies observed
      notable benefits associated with the inclusion of spatial and temporal
      correlation and their interactions. However, the safety literature lacks
      sufficient research for the comparison of different temporal treatments and their
      interaction with spatial component. This study developed four spatiotemporal
      models with varying complexity due to the different temporal treatments such as
      (I) linear time trend; (II) quadratic time trend; (III) Autoregressive-1 (AR-1);
      and (IV) time adjacency. Moreover, the study introduced a flexible two-component
      mixture for the space-time interaction which allows greater flexibility compared
      to the traditional linear space-time interaction. The mixture component allows
      the accommodation of global space-time interaction as well as the departures from
      the overall spatial and temporal risk patterns. This study performed a
      comprehensive assessment of mixture models based on the diverse criteria
      pertaining to goodness-of-fit, cross-validation and evaluation based on in-sample
      data for predictive accuracy of crash estimates. The assessment of model
      performance in terms of goodness-of-fit clearly established the superiority of
      the time-adjacency specification which was evidently more complex due to the
      addition of information borrowed from neighboring years, but this addition of
      parameters allowed significant advantage at posterior deviance which subsequently
      benefited overall fit to crash data. The Base models were also developed to study
      the comparison between the proposed mixture and traditional space-time components
      for each temporal model. The mixture models consistently outperformed the
      corresponding Base models due to the advantages of much lower deviance. For cross
      validation comparison of predictive accuracy, linear time trend model was
      adjudged the best as it recorded the highest value of log pseudo marginal
      likelihood (LPML). Four other evaluation criteria were considered for typical
      validation using the same data for model development. Under each criterion,
      observed crash counts were compared with three types of data containing Bayesian
      estimated, normal predicted, and model replicated ones. The linear model again
      performed the best in most scenarios except one case of using model replicated
      data and two cases involving prediction without including random effects. These
      phenomena indicated the mediocre performance of linear trend when random effects
      were excluded for evaluation. This might be due to the flexible mixture space
      time interaction which can efficiently absorb the residual variability escaping
      from the predictable part of the model. The comparison of Base and mixture models
      in terms of prediction accuracy further bolstered the superiority of the mixture
      models as the mixture ones generated more precise estimated crash counts across
      all four models, suggesting that the advantages associated with mixture component
      at model fit were transferable to prediction accuracy. Finally, the residual
      analysis demonstrated the consistently superior performance of random effect
      models which validates the importance of incorporating the correlation structures
      to account for unobserved heterogeneity.

PMID- 29324266
TI  - Collision risk analysis based train collision early warning strategy.
AB  - A Train Collision Early Warning System (TCEWS) has been developed for collision
      avoidance. However, there are few studies regarding how to evaluate the collision
      risk and provide an early warning concerning a preceding train on the railway. In
      this paper, we have found that the time for collision avoidance is constrained by
      the timing of events, such as wireless communication latency, driver reaction,
      safety protection distance and deceleration rate. Considering these timing
      components, the time to avoid a collision is calculated accurately. To evaluate
      the potential collision severity when the following train approaches, the
      collision risk is defined based on the time to avoid a collision. The train
      collision early warning signal is divided into a four-tier color-coded system
      based on the collision risk, with red representing the most severe collision
      risk, followed by orange, yellow and blue. A field test of the train collision
      early warning strategy on the Hankou-Yichang Railway is analysed. It is
      demonstrated that the strategy has sufficient capability to indicate a potential
      collision and warn the following train.

PMID- 29324267
TI  - Clinical validity of the Japanese version of WAIS-III short forms: Adaptation for
      patients with mild neurocognitive disorder and dementia.
AB  - We investigated the Japanese WAIS-III short form utility in mild neurocognitive
      disorder and dementia. Our sample consisted of 108 old patients (ages: 65-89;
      mean age = 78.3). Fifteen short forms (SFs) and full-scale (FS) IQs were
      compared. The SFs included Dyads (SF1, SF2), Triads (SF3), Tetrads (SF4, SF5,
      SF6, SF7), Pentad (SF8), Six-subtest (SF9), Seven-subtests (SF10(a)(b),
      SF11(a)(b), SF12), and Nine-subtest (SF13). Correlations between SFIQs and FSIQ
      were all significant. Significant differences also were found in paired t-test
      between FSIQ and 5 SFIQs (SF2: t = -4.16, SF5: t = -7.06, SF7; t = 2.59, SF10(a):
      t = 2.56, SF12: t = -4.82; p < .05). On the point of clinical accuracy, two SFs
      led to an appropriate estimated IQ (SF11(a): 84.3%, SF13: 91.7%; within 95%
      confidence interval and 2 standard error of measurements of FSIQ). However, SF13
      was considered to still have a long administration time. The present results
      suggest that SF11(a) could be the most useful to estimate IQ for Japanese
      speaking patients with mild neurocognitive disorder and dementia. SF11(a)
      consists of seven subtests of Similarities, Arithmetic, Digit Span, Information,
      Picture Completion, Digit Symbol-Coding, and Matrix Reasoning (Ryan & Ward,
      1999), and the formula (Axelrod et al., 2001) should be adopted to convert scaled
      scores into estimated IQ scores.

PMID- 29324268
TI  - Exploring the role of YouTube in delivering dementia education to older Chinese.

PMID- 29324269
TI  - Surfactant-free synthesis of silica aerogel microspheres with hierarchically
      porous structure.
AB  - In this work, we developed a new method to synthesize silica aerogel microspheres
      via ambient pressure drying (APD) process without applying any surfactants and
      mechanical stirring. An ethanol solution of partially hydrolyzed, partially
      condensed silica (CS) was used as precursor in the synthesis, the water-repellent
      n-Heptane as solvent, while the water-soluble ammonia gas (NH3) as catalyst.
      After a fast sol-gel process and APD process, aerogel microspheres were obtained
      in the form of white powder with packing density ranged from 62 mg/cm3 to 230
      mg/cm3 for different samples. The SEM images exhibited fine spherical morphology
      for these aerogel microparticles, and their statistical average particle diameter
      ranged from 0.8 MUm to 1.5 MUm. Besides, according to the analysis of N2
      adsorption-desorption isotherms, the BET surface area of these aerogel
      microspheres was in the range of 800-960 m2/g, and a considerable volume of
      micropores was detected along with the abundant mesospores in these microspheres,
      which was further confirmed by the TEM image and SAXS curve. Based on the very
      limited solubility of NH3 in the reaction system, a non-emulsion formation
      mechanism was proposed to illustrate the formation of these aerogel microspheres.

PMID- 29324270
TI  - AgCl/Ag3PO4: A stable Ag-Based nanocomposite photocatalyst with enhanced
      photocatalytic activity for the degradation of parabens.
AB  - An AgCl/Ag3PO4 composite has been successfully fabricated by a simple desorption
      precipitation method. Scanning electron microscopy (SEM), transmission electron
      microscopy (TEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy
      (XPS), ultraviolet-visible spectroscopy (UV/Vis), and photoluminescence (PL) have
      been used to study the structural and physicochemical characteristics of the
      AgCl/Ag3PO4 composite. The photocatalytic activity of the AgCl/Ag3PO4 composite
      has been tested by the degradation of parabens under visible-light irradiation.
      100% of MPB was degraded within 40 min in the AgCl/Ag3PO4-visible light system.
      Moreover, the photocatalytic activity of AgCl/Ag3PO4 remained at 94% of the
      original level after five runs, which was much higher than that of pure Ag3PO4
      (25%). The obtained results confirmed that the AgCl/Ag3PO4 composite exhibited
      significantly higher photocatalytic performance and improved stability compared
      with bare Ag3PO4. The enhanced photocatalytic performance of the AgCl/Ag3PO4
      composite could be mainly attributed to highly efficient charge separation
      through a synergistic effect of AgCl, Ag3PO4, and in situ photo-reduced Ag
      nanoparticles. Trapping experiments confirmed h+ and .O2- to be the two main
      active species in the photocatalytic process. Finally, a possible photocatalytic
      mechanism for the charge-transfer process is proposed to account for the enhanced
      photocatalytic performance of the AgCl/Ag3PO4 composite.

PMID- 29324271
TI  - Bifunctional monomer magnetic imprinted nanomaterials for selective separation of
      tetracyclines directly from milk samples.
AB  - Novel magnetic molecularly imprinted nanomaterials (DA + BSA-MMIPs) were prepared
      adopting bovine serum albumin (BSA) and dopamine as bifunctional monomers for the
      first time. Besides the role of assistant functional monomer, BSA can exclude the
      proteins with like charges and promote low molecular weight tetracyclines to be
      adsorbed. Thus, the DA + BSA-MMIPs could fulfil the selective separation of
      tetracyclines directly from milk samples. The characteristics, polymerization
      conditions, and adsorption performances of the resultant nanomaterials were
      investigated in detail. In addition of uniform imprinting layers, stable
      crystalline phase, and good magnetism of the DA + BSA-MMIPs, they have rapid
      binding kinetic, high adsorption capacity, and favorable reusability. The
      imprinted nanomaterials were coupled with HPLC to selectively extract and
      determine trace tetracyclines from untreated milk samples. The recoveries of
      tetracyclines are in the range of 84.1-95.8% with relative standard deviations of
      less than 6.7%. The developed method is especially suitable for the selective
      enrichment and detection of target compounds directly from a complex sample with
      proteins.

PMID- 29324272
TI  - Violence and maltreatment in Tanzanian families-Findings from a nationally
      representative sample of secondary school students and their parents.
AB  - Though the Sustainable Development Goals of the United Nations aim to end all
      forms of violence against minors, child maltreatment remains a globally prevalent
      phenomenon. Despite the fact that parents in numerous countries apply violent
      discipline methods to control children's behavior, little is known about the
      prevalence of maltreatment and violent discipline in Sub-Saharan Africa. In this
      study, we examined the prevalence of maltreatment and violent discipline from
      both the adolescents' and parents' perspectives. In addition, we explored risk
      factors that could be associated with violent discipline by parents. We
      administered questionnaires to a nationally representative sample of 700
      Tanzanian secondary school students (52% girls, mean age: 14.92 years, SD = 1.02,
      range: 12-17) and 333 parents or primary guardians (53% females; mean age: of
      43.47 years, SD = 9.02, range: 19-71). More than 90% of all students reported
      exposure to violent discipline by a parent within the past year. Concurrently,
      more than 80% of parents acknowledged using violent discipline techniques. Using
      a path model, we found that violent discipline by parents was associated with
      parental stress. Other risk factors contributed to a higher stress level but were
      not directly linked to maltreatment. Our findings indicate high levels of violent
      discipline in Tanzanian families. There is a pressing need to design and
      implement interventions that prevent children from experiencing violence at home.
      Reducing parents' stress levels may be a starting point for intervention. Yet,
      due to the high levels of violent discipline, societal beliefs also need to be
      considered.

PMID- 29324273
TI  - A situational crime prevention analysis of Anglican clergy's child protective
      practices.
AB  - To date, a predominant focus within the field of 'clerical collar crime' has
      revolved around institutional-level church responses to child sexual abuse
      events, survivors and offenders. Comparatively, little attention has been
      directed towards the micro-level and in particular, examining clerical responses
      to child sexual abuse. This article presents empirical findings concerning the
      'everyday' child protective practices of Anglican clergy in the Diocese of
      Tasmania, Australia. Research data was acquired through open-ended qualitative
      interviews conducted with a sample of 34 clergy in a broader study of clerical
      culture, habitus and life amidst the 'church abuse crisis'. The framework of
      Situational Crime Prevention is employed to evaluate the feasibility of clergy's
      child-safe practices and comment on how these practices could be further altered
      through professional development. Research findings demonstrate that clergy
      possess an active awareness of risk, and execute a series of protective measures
      to minimise both sexual interactions with children and allegations of
      impropriety.

PMID- 29324274
TI  - Mediators between adverse childhood experiences and suicidality.
AB  - We investigated whether psychiatric symptomatology, impulsivity, family and
      social dysfunction, and alcohol use mediate the relationship between adverse
      childhood experiences (ACEs) and suicidality. The study population comprised 206
      adolescent psychiatric inpatients and 203 age- and gender-matched adolescents
      from the community. ACEs and suicidality were assessed using the Schedule for
      Affective Disorders and Schizophrenia for School-Age Children - Present and
      Lifetime version, the Life Events Checklist, and a structured background data
      collection sheet. Psychiatric symptomatology was measured using the Symptom
      Checklist -90. Impulsivity, social dysfunction, and family dysfunction were
      measured using the Offer Self-Image Questionnaire, and alcohol use was assessed
      with the Alcohol Use Disorders Identification Test. A simple mediation test and
      multiple mediation analyses were conducted. A positive direct effect of ACEs on
      suicidality was observed. Also seen was a positive indirect effect of ACEs on
      suicidality through psychiatric symptomatology, impulsivity, and family and
      social dysfunctions. Alcohol misuse did not, however, mediate the relationship
      between ACEs and suicidality. According to the multiple mediation analyses,
      psychiatric symptomatology was the most significant mediator, followed by
      impulsivity. Psychiatric symptoms, impulsivity, and family and social
      dysfunctions are factors that should be taken into consideration when assessing
      suicidality in adolescents.

PMID- 29324275
TI  - Effective usage of sorghum bagasse: Optimization of organosolv pretreatment using
      25% 1-butanol and subsequent nanofiltration membrane separation.
AB  - We investigated the use of low concentrations of butanol (<40%, all v/v) as an
      organosolv pretreatment to fractionate lignocellulosic biomass into cellulose,
      hemicellulose, and lignin. The pretreatment conditions were optimized for sorghum
      bagasse by focusing on four parameters: butanol concentration, sulfuric acid
      concentration, pretreatment temperature, and pretreatment time. A butanol
      concentration of 25% or higher together with 0.5% or higher acid was effective
      for removing lignin while retaining most of the cellulose in the solid fraction.
      The highest cellulose (84.9%) and low lignin (15.3%) content were obtained after
      pretreatment at 200  degrees C for 60 min. Thus, pretreatment comprising 25%
      butanol, 0.5% acid, 200  degrees C, and 60 min process time was considered
      optimal. Enzymatic saccharification and fermentation by Saccharomyces cerevisiae
      produced 61.9 g/L ethanol from 200 g/L solid fraction obtained following
      pretreatment, and 10.2 g/L ethanol was obtained from the liquid fraction by
      xylose-utilizing S. cerevisiae following membrane nanofiltration to remove
      butanol.

PMID- 29324276
TI  - Furfural production from biomass pretreatment hydrolysate using vapor-releasing
      reactor system.
AB  - Biomass hydrolysate from autohydrolysis pretreatment was used for furfural
      production considering it is in rich of xylose, xylo-oligomers, and other
      decomposition products from hemicellulose structure. By using the vapor-releasing
      reactor system, furfural was protected from degradation by separating it from the
      reaction media. The maximum furfural yield of 73% was achieved at 200  degrees C
      for biomass hydrolysate without the use of the catalyst. This is because the
      presence of organic acids such as acetic acid in hydrolysate functioned as a
      catalyst. According to the results in this study, biomass hydrolysate with a
      vapor-releasing system proves to be efficient for furfural production. The
      biorefinery process which allows the separation of xylose-rich autohydrolysate
      from other parts from biomass feedstock also improves the overall application of
      the biomass.

PMID- 29324277
TI  - Readmission in psychiatry inpatients within a year of discharge: The role of
      symptoms at discharge and post-discharge care in a Brazilian sample.
AB  - INTRODUCTION: Readmission into inpatient psychiatric beds is a useful outcome for
      patients, care providers, and policymakers. This study aims to investigate the
      role of level of symptoms at discharge and type of post-discharge care in
      determining readmissions after a year before a psychiatric admission. METHODS: We
      performed a prospective and observational study in a general hospital psychiatric
      facility. Patients were assessed at admission, discharge, and one year after
      discharge. We used a multivariable logistic regression to determine predictors of
      readmission. RESULTS: In total, 488 patients were included at admission, and 401
      (82,17%) were accessed in the follow-up period. Psychiatric readmissions occurred
      in 29.17% of the followed patients. The number of previous admissions represents
      a 38% higher chance of being readmitted (OR 1.38; CI 1.16-1.60). For patients
      admitted in a depressive episode, not being in remission at discharge increases
      140% the chance to be readmitted (OR 2.40; CI 1.14-5.07) as well as the follow-up
      at primary (OR 5.27; CI 1.06-26.15). For those with Schizophrenia and related
      disorders, higher scores in BPRS at discharge increases the chance to be
      readmitted (OR 1.28, CI 1.11-1.48). CONCLUSION: Level of symptoms at discharge
      was related to higher chance to be readmitted in patients admitted in a
      depressive episode and those with schizophrenia and related disorders. Findings
      of the type of care raise the need for further investigation. Also, this finding
      confirms the importance of the history of previous admissions in predicting
      future admissions.

PMID- 29324279
TI  - Inhibition of UDP-glucose dehydrogenase by 6-thiopurine and its oxidative
      metabolites: Possible mechanism for its interaction within the bilirubin
      excretion pathway and 6TP associated liver toxicity.
AB  - 6-Thiopurine (6TP) is an actively prescribed drug in the treatment of various
      diseases ranging from Crohn's disease and other inflammatory diseases to acute
      lymphocytic leukemia and non-Hodgkin's leukemia. While 6TP has beneficial
      therapeutic uses, severe toxicities are also reported with its use, such as
      jaundice and liver toxicity. While numerous investigations into the mode in which
      toxicity originates has been undertaken. None have investigated the effects of
      inhibition towards UDP-Glucose Dehydrogenase (UDPGDH), an oxidative enzyme
      responsible for UDP-glucuronic acid (UDPGA) formation or UDP-Glucuronosyl
      transferase (UGT1A1), which is responsible for the conjugation of bilirubin with
      UDPGA for excretion. Failure to excrete bilirubin leads to jaundice and liver
      toxicity. We proposed that either 6TP or its primary oxidative excretion
      metabolites inhibit one or both of these enzymes, resulting in the observed
      toxicity from 6TP administration. Inhibition analysis of these purines revealed
      that 6-thiopurine has weak to no inhibition towards UDPGDH with a Ki of 288 MUM
      with regard to varying UDP-glucose, but 6-thiouric (primary end metabolite, fully
      oxidized at carbon 2 and 8, and highly retained by the body) has a near six-fold
      increased inhibition towards UDPGDH with a Ki of 7 MUM. Inhibition was also
      observed by 6-thioxanthine (oxidized at carbon 2) and 8-OH-6TP with Ki values of
      54 and 14 MUM, respectively. Neither 6-thiopurine or its excretion metabolites
      were shown to inhibit UGT1A1. Our results show that the C2 and C8 positions of
      6TP are pivotal in said inhibition towards UDPGDH and have no effect upon UGT1A1,
      and that blocking C8 could lead to new analogs with reduced, if not eliminated
      jaundice and liver toxicities.

PMID- 29324278
TI  - Oleanane-type triterpenoid saponins from Lysimachia fortunei Maxim.
AB  - Six previously undescribed oleanane-type triterpenoid saponins, fortunosides A-F,
      together with six known ones, were isolated from the aerial parts of Lysimachia
      fortunei Maxim. Their structures were established by spectroscopic data analyses
      (1D, 2D-NMR and HRESIMS) and chemical methods. All isolated triterpenoid saponins
      were evaluated for their cytotoxicity against four human liver cancer cell lines
      (SMMC-7721, Hep3B, HuH7, and SK-Hep-1). Three saponins with the aglycone
      protoprimulagenin A exhibited moderate cytotoxicity against all of the tested
      human cancer cell lines, with IC50 values ranging from 4.76 to 15.12 MUM.

PMID- 29324280
TI  - Effective phospholipids removing microelution-solid phase extraction LC-MS/MS
      method for simultaneous plasma quantification of aripiprazole and dehydro
      aripiprazole: Application to human pharmacokinetic studies.
AB  - A simple liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has
      been developed and validated for simultaneous quantification of aripiprazole and
      its active metabolite, dehydro-aripiprazole, in human plasma. Stable isotopically
      labeled aripiprazole, aripiprazole-D8, has been used as the internal standard
      (IS) for both analytes. Only 200 MUl of human plasma was needed for analyte
      extraction, using effective phospholipids-eliminating three-step microelution
      solid-phase extraction (SPE, Oasis PRiME HLB 96-well MUElution Plate). An ACE C18
      PFP column was applied for chromatographic separation at 25  degrees C, protected
      by a 0.2-MUm on-line filter. A combination of ammonium formate (5 mM)
      acetonitrile (pH 4.0; 65:35, v/v) was used as mobile phase and the chromatogram
      was run under gradient conditions at a flow rate of 0.6 ml/min. Run time lasted 5
      min, followed by a re-equilibration time of 3 min, to give a total run time of 8
      min. Five MUl of the sample was injected into the chromatographic system.
      Aripiprazole, dehydro-aripiprazole and IS were detected using the mode multiple
      reaction monitoring in the positive ionization mode. The method was linear in the
      concentration range of 0.18-110 ng/ml and 0.35-100 ng/ml for aripiprazole and
      dehydro-aripiprazole, respectively. Our method has been validated according to
      the recommendations of regulatory agencies through tests of precision, accuracy,
      recovery, matrix effect, stability, sensitivity, selectivity and carry-over. Our
      microelution-SPE method removes more than 99% of main plasma phospholipids
      compared to protein precipitation and was successfully applied to several
      bioequivalence studies.

PMID- 29324281
TI  - Chemical profiling of Euphorbia fischeriana Steud. by UHPLC-Q/TOF-MS.
AB  - Ultra-high-performance liquid chromatography coupled with quadrupole/time-of
      flight mass spectrometry (UHPLC-Q/TOF-MS) in positive ion mode was used to
      profile and identify the major constituents in Euphorbia fischeriana Steud. (E.
      fischeriana). An Agilent ZORBAX SB-C18 column was used to separate the crude
      extract of E. fischeriana, and the mobile phases were acetonitrile and 0.1%
      aqueous formic acid (v/v). A total of 40 peaks were detected, and 37 components,
      including phloroglucinol derivatives, diterpenoids and nitrogenous compounds,
      were identified based on their accurate masses and fragmentation characteristics.
      The chemical structures of 7 of the detected compounds were determined by
      comparing standard compounds to the compounds that were isolated from E.
      fischeriana. Reasonable fragmentation mechanisms and key fragment ions of the
      four jolkinolide components were determined to aid in the identification of the
      other diterpenoids in E. fischeriana. In addition, the compound corresponding to
      peak 18, namely, jolkinomethylide, was determined to be new, and its chemical
      structure was determined and elucidated based on MS and NMR spectroscopic data.
      The present study provided valuable information on the new components in E.
      fischeriana and established a practical method for evaluating the quality of E.
      fischeriana.

PMID- 29324282
TI  - Influence of glycan modification on IgG1 biochemical and biophysical properties.
AB  - Monoclonal antibodies (mAbs) are the fastest growing class of biopharmaceuticals.
      The specific therapeutic tasks vary among different mAbs, which may include
      neutralization of soluble targets, activation of cytotoxic pathways, targeted
      drug delivery, and diagnostic imaging. The specific therapeutic goal defines
      which interactions of the antibody with its multiple physiological partners are
      most critical for function, and which ones are irrelevant or indeed detrimental.
      In this work, we explored the ability of the glycan chains to affect IgG1
      interaction with two key receptor families, FcRn and gamma-type Fc receptors, as
      well as the influence of glycan composition on the conformation and stability of
      the antibody molecule. Three different glycan-modified forms of IgG1 (fully
      deglycosylated, hypergalactosylated and hypersialylated) were produced and
      characterized alongside the unmodified mAb molecule. Biophysical measurements did
      not reveal any changes that would be indicative of alterations in the higher
      order structure or increased aggregation propensity for any of the three
      glycoforms compared to the unmodified mAb, although the CH2 domain was shown to
      have reduced thermal stability in the fully deglycosylated form. No significant
      changes were observed for the hypergalactosylated and hypersialylated forms of
      IgG1 with regards to binding to FcRn, FcgammaRIIA and FcgammaRIIIA, suggesting
      that neither half-life in circulation nor their ability to induce an immune
      response are likely to be affected by these modifications of the glycan chains.
      In contrast, no measurable binding was observed for the deglycosylated form of
      IgG1 with either FcgammaRIIA or FcgammaRIIIA, although this form of the antibody
      retained the ability to associate with FcRn. These highly specific patterns of
      attenuation of Fc receptor recognition can be exploited in the future for
      therapeutic purposes.

PMID- 29324283
TI  - A novel electrochemiluminescent biosensor based on resonance energy transfer
      between poly(9,9-di-n-octylfluorenyl-2,7-diyl) and 3,4,9,10-perylenetetracar
      boxylic acid for insulin detection.
AB  - An electrochemiluminescencent (ECL) biosensor was designed for the determination
      of insulin using a novel ECL resonance energy transfer (ECL-RET) strategy. In
      this strategy, carboxyl poly(9,9-dioctyfluorenyl-2,7-diyl) dots (PFO dots) were
      worked as ECL donor and 3,4,9,10-perylenetetracar-boxylic acid (PTCA) exploited
      as ECL acceptor, and hydrogen peroxide (H2O2) employed as the coreactant. The ECL
      donor and ECL acceptor were separately labeled with primary antibody (Ab1) and
      secondary antibody (Ab2), forming a sensing interface to the analyte target,
      insulin. In this expected sandwich-type ECL biosensor, PFO dots acted as sensing
      platform and PTCA employed as labels to quench the ECL emission of PFO dots.
      During the determination process, ECL signal of PFO dots was decreased in a
      gradual way by the increase of insulin concentration, and the quenching mechanism
      was also investigated. Under the optimal experimental conditions, the constructed
      biosensor exhibited an excellent performance, including a wide linear range from
      1.0 * 10-5ng/mL to 1.0 * 102ng/mL, low detection limit of 3.0 * 10-6ng/mL, good
      stability and selectivity for the detection of insulin. This pair of PFO-PTCA, as
      a new donor-acceptor pair in ECL-RET system, would provide a promising platform
      for bioanalysis in ECL field.

PMID- 29324284
TI  - A novel cytosensor based on Pt@Ag nanoflowers and AuNPs/Acetylene black for
      ultrasensitive and highly specific detection of Circulating Tumor Cells.
AB  - Circulating tumor cells (CTCs), as the cellular origin of metastasis, are cancer
      cells that break away from a primary tumor and circulate in the peripheral blood.
      And they provide a wealth of information about tumor phenotype. Here, this work
      reported a novel ultrasensitive immunoassay protocol for the detection of CTCs by
      using Pt@Ag nanoflowers (Pt@AgNFs) and AuNPs/Acetylene black (AuNPs/AB)
      nanomaterial. In the established approach, AuNPs/AB nanomaterial was used as
      substrate material to increase the specific surface area and enhance the
      conductivity of the gold electrode. Protein G was used for oriented
      immobilization of capture antibody, which strongly improved the capture
      efficiency of MCF-7 cells. The innovatively synthesized Pt@AgNFs by our group
      with high specific surface area and good biocompatibility were not only as the
      carriers of signal antibodies (Ab2) but also catalyzed the reduction of H2O2,
      which effectually amplified the current signal. A linear relationship between
      current signals and the concentrations of CTCs was obtained in the range from 20
      to 1*106 cells mL-1 and the detection limit is as low as 3 cells mL-1 on
      condition of acceptable stability and reproducibility. Furthermore, the as
      proposed cytosensor showed excellent performance in the detection of CTCs in
      human blood samples. These results suggest that the proposed cytosensor will be a
      promising application for accurately quantitative detection of CTCs.

PMID- 29324285
TI  - Lithium as an emerging environmental contaminant: Mobility in the soil-plant
      system.
AB  - Contamination of soil with lithium (Li) is likely to increase due to its wider
      dispersal in the environment, associated in particular, with the disposal of the
      now ubiquitous Li-ion batteries. There is, however, a paucity of information on
      the behaviour of Li in the soil-plant system. We measured the sorption of added
      Li to soil, and uptake of Li by food and fodder species. Around New Zealand, soil
      concentrations were shown to range from 0.08 mg/kg to 92 mg/kg, and to be
      positively correlated with clay content. Most geogenic Li in soil is insoluble
      and hence unavailable to plants but, when Li+ is added to soil, there is only
      limited sorption of Li. We found that Li sorption increased with increasing soil
      pH, and decreased proportionately with increasing Li concentrations. Compared to
      other cations in soil, Li is mobile and may leach into receiving waters, be taken
      up by plants, or have other biological impacts. In a soil spiked with just 5
      mg/kg, plants took up several hundred mg/kg Li into leaves with no reduction in
      biomass. Lithium appears to be a phloem immobile element, with the highest
      concentrations occurring in the older leaves and the lowest concentrations
      occurring in the seeds or fruits. These results may raise concerns and risks in
      situations where food and fodder crops are associated with waste disposal.

PMID- 29324286
TI  - Digit ratio (2D:4D) and circulating testosterone, oestradiol, and progesterone
      levels across the menstrual cycle.
AB  - BACKGROUND: Digit ratio (2D:4D) is used by researchers as an indicator of
      prenatal sex hormone exposure. Two previous studies have examined associations
      between 2D:4D and circulating sex steroid concentrations across the menstrual
      cycle in adult females. One reported that digit ratio correlated positively with
      oestradiol levels, whereas the other found no such effect; neither observed
      significant associations with progesterone. AIMS: To examine associations between
      2D:4D, as well as asymmetry (i.e. right minus left 2D:4D), and circulating sex
      steroids across the menstrual cycle. STUDY DESIGN: Correlational. SUBJECTS: 32
      naturally cycling adult females from rural southern Poland. OUTCOME MEASURES:
      Salivary oestradiol, progesterone, testosterone, and testosterone to oestradiol
      ratio (T:O) measured during the follicular, peri-ovulatory, and luteal phases.
      Average levels across the cycle were also examined. RESULTS AND CONCLUSIONS:
      Asymmetry in digit ratio correlated positively with oestradiol at each phase, as
      well as with average levels across the cycle. Each association, other than that
      relating to average levels, remained statistically significant after a range of
      covariates had been controlled for. No other significant correlations were
      observed between digit ratio variables and circulating hormone levels. Our
      results might suggest that low exposure to androgens and/or high exposure to
      oestrogens during gestation is a predictor of high oestradiol levels in naturally
      cycling females of reproductive age. However, considering that it was asymmetry
      in digit ratio, and not either right or left 2D:4D, that was a significant
      predictor, it is also possible that these effects reflect more general
      associations between bilateral asymmetry and circulating oestradiol levels.

PMID- 29324287
TI  - Expression of heterologous transporters in Saccharomyces kudriavzevii: A strategy
      for improving yeast salt tolerance and fermentation performance.
AB  - S. kudriavzevii has potential for fermentations and other biotechnological
      applications, but is sensitive to many types of stress. We tried to increase its
      tolerance and performance via the expression of various transporters from
      different yeast species. Whereas the overexpression of Z. rouxii fructose uptake
      systems (ZrFfz1 and ZrFsy1) or a glycerol importer (ZrStl1) did not improve the
      ability of S. kudriavzevii to consume fructose and survive osmotic stress, the
      expression of alkali-metal-cation exporters (ScEna1, ScNha1, YlNha2) improved S.
      kudriavzevii salt tolerance, and that of ScNha1 also the fermentation
      performance. The level of improvement depended on the type and activity of the
      transporter suggesting that the natural sensitivity of S. kudriavzevii cells to
      salts is based on a non-optimal functioning of its own transporters.

PMID- 29324288
TI  - Description of an orthologous cluster of ochratoxin A biosynthetic genes in
      Aspergillus and Penicillium species. A comparative analysis.
AB  - Ochratoxin A (OTA) is one of the most important mycotoxins due to its toxic
      properties and worldwide distribution which is produced by several Aspergillus
      and Penicillium species. The knowledge of OTA biosynthetic genes and
      understanding of the mechanisms involved in their regulation are essential. In
      this work, we obtained a clear picture of biosynthetic genes organization in the
      main OTA-producing Aspergillus and Penicillium species (A. steynii, A.
      westerdijkiae, A. niger, A. carbonarius and P. nordicum) using complete genome
      sequences obtained in this work or previously available on databases. The results
      revealed a region containing five ORFs which predicted five proteins: halogenase,
      bZIP transcription factor, cytochrome P450 monooxygenase, non-ribosomal peptide
      synthetase and polyketide synthase in all the five species. Genetic synteny was
      conserved in both Penicillium and Aspergillus species although genomic location
      seemed to be different since the clusters presented different flanking regions
      (except for A. steynii and A. westerdijkiae); these observations support the
      hypothesis of the orthology of this genomic region and that it might have been
      acquired by horizontal transfer. New real-time RT-PCR assays for quantification
      of the expression of these OTA biosynthetic genes were developed. In all species,
      the five genes were consistently expressed in OTA-producing strains in permissive
      conditions. These protocols might favour futures studies on the regulation of
      biosynthetic genes in order to develop new efficient control methods to avoid OTA
      entering the food chain.

PMID- 29324289
TI  - Phylogenetic analysis reveals three distinct epidemiological profiles in Dutch
      and Flemish blood donors with hepatitis B virus infection.
AB  - During 2006-2016, hepatitis B virus (HBV) was detected in nearly 400 blood donors
      in the Netherlands and Flanders. Donor demographics and self-reported risk
      factors as disclosed during the donor exit interview were compared to HBV
      phylogenies of donor and reference sequences. First-time donors with chronic HBV
      infection were often immigrants (67%) infected with genetically highly diverse
      strains of genotypes A (32%), B (8%), C (6%), D (53%) and E to H (1%). Each
      subtype was strongly associated with donor ethnicity. In contrast, 57/62 (93%) of
      acute/recent HBV infections occurred among indigenous donors, of whom 67% was
      infected with one specific widely circulating epidemic HBV-A2 lineage. HBV typing
      identified three distinct epidemiological profiles: the import of chronic HBV
      infections through migration, longstanding transmission of non-epidemic HBV-A2
      strains within western-Europe, and the active transmission of one epidemic HBV-A2
      strain most likely fueled by sexual risk behavior.

PMID- 29324290
TI  - Ross River virus envelope glycans contribute to disease through activation of the
      host complement system.
AB  - Mannose binding lectin (MBL) generally plays a protective role during viral
      infection, yet MBL-mediated complement activation promotes Ross River virus (RRV)
      induced inflammatory tissue destruction, contributing to arthritis and myositis.
      As MBL binds to carbohydrates, we hypothesized that N-linked glycans on the RRV
      envelope glycoproteins act as ligands for MBL. Using a panel of RRV mutants
      lacking the envelope N-linked glycans, we found that MBL deposition onto infected
      cells was dependent on the E2 glycans. Moreover, the glycan-deficient viruses
      exhibited reduced disease and tissue damage in a mouse model of RRV-induced
      myositis compared to wild-type RRV, despite similar viral load and inflammatory
      infiltrates within the skeletal muscle. Instead, the reduced disease induced by
      glycan-deficient viruses was linked to decreased MBL deposition and complement
      activation within inflamed tissues. These results demonstrate that the viral N
      linked glycans promote MBL deposition and complement activation onto RRV-infected
      cells, contributing to the development of RRV-induced myositis.

PMID- 29324292
TI  - Use of sperm DNA integrity as a marker for exposure to contamination in Palaemon
      serratus (Pennant 1777): Intrinsic variability, baseline level and in situ
      deployment.
AB  - In a previous study, the Comet assay was optimized for Palaemon serratus prawns
      in order to propose a biomarker for sperm quality in this species. However,
      better knowledge of its basal level and its natural variability, related to
      intrinsic biotic and environmental abiotic factors, is required before any
      relevant use of this biomarker in the field. To fulfill this goal, the present
      study proceeded in three steps: (i) the temporal variability of DNA integrity was
      followed monthly in a reference population over a 2-year period, (ii) the
      correlation between the main intrinsic biotic (i.e. size, weight and molting
      stage) and abiotic factors (i.e. water temperature) were recorded in the field,
      and the basal DNA integrity was assessed in order to scrutinize any confounding
      influence of factors unrelated to toxic response, (iii) the baseline level was
      used to discriminate biomarker response among different stations displaying
      contrasting contamination levels. The results of the two-year monitoring in the
      reference population revealed no correlation between the levels of spermatozoa
      DNA damage and temperature, body size, weight or molting stage. Only a slight
      variability between monthly samplings was detected. On the basis of these field
      collected data, we defined a reference distribution (i.e. 52.6 +/- 5.6 A.U) with
      a threshold value (i.e. 61.7 A.U). Finally, this threshold value proved its
      relevance to discriminate among stations with contrasting pollution levels around
      the Seine Bay. Indeed, the results suggest significant DNA damage in populations
      nearest the Seine estuary, a major source of contaminants in the Bay, and a lower
      effect in populations further away from the estuary. The overall conclusion was
      that the Comet assay on P. serratus spermatozoa could be a useful tool for the
      monitoring of the toxicological print within sperm and main globally the
      contamination exposure of crustaceans in marine waters.

PMID- 29324293
TI  - Biofilms, active substrata, and me.
AB  - Having worked with biofilms since the 1970s, I know that they are ubiquitous in
      nature, of great value in water technology, and scientifically fascinating.
      Biofilms are naturally able to remove BOD, transform N, generate methane, and
      biodegrade micropollutants. What I also discovered is that biofilms can do a lot
      more for us in terms of providing environmental services if we give them a bit of
      help. Here, I explore how we can use active substrata to enable our biofilm
      partners to provide particularly challenging environmental services. In
      particular, I delve into three examples in which an active substratum makes it
      possible for a biofilm to accomplish a task that otherwise seems impossible. The
      first example is the delivery of hydrogen gas (H2) as an electron donor to drive
      the reduction and detoxification of the rising number of oxidized contaminant:
      e.g., perchlorate, selenate, chromate, chlorinated solvents, and more. The active
      substratum is a gas-transfer membrane that delivers H2 directly to the biofilm in
      a membrane biofilm reactor (MBfR), which makes it possible to deliver a low
      solubility gaseous substrate with 100% efficiency. The second example is the
      biofilm anode of a microbial electrochemical cell (MxC). Here, the anode is the
      electron acceptor for anode-respiring bacteria, which "liberate" electrons from
      organic compounds and send them ultimately to a cathode, where we can harvest
      valuable products or services. The anode's potential is a sensitive tool for
      managing the microbial ecology and reaction kinetics of the biofilm anode. The
      third example is intimately coupled photobiocatalysis (ICPB), in which we use
      photocatalysis to enable the biodegradation of intrinsically recalcitrant organic
      pollutants. Photocatalysis transforms the recalcitrant organics just enough so
      that the products are rapidly biodegradable substrates for bacteria in a nearby
      biofilm. The macroporous substratum, which houses the photocatalyst on its
      exterior, actively provides donor substrate and protects the biofilm from UV
      light and free radicals in its interior. These three well-developed topics
      illustrate how and why an active substratum expands the scope of what biofilms
      can do to enhance water sustainability.

PMID- 29324291
TI  - Disulfide-masked iron prochelators: Effects on cell death, proliferation, and
      hemoglobin production.
AB  - The iron metabolism of malignant cells, which is altered to ensure higher
      acquisition and utilization, motivates the investigation of iron chelation
      strategies in cancer treatment. In a prochelation approach aimed at increasing
      intracellular specificity, disulfide reduction/activation switches are
      incorporated on iron-binding scaffolds resulting in intracellularly activated
      scavengers. Herein, this strategy is applied to several tridentate donor sets
      including thiosemicarbazones, aroylhydrazones and semicarbazones. The novel
      prochelator systems are antiproliferative in breast adenocarcinoma cell lines
      (MCF-7 and metastatic MDA-MB-231) and do not result in the intracellular
      generation of oxidative stress. Consistent with iron deprivation, the tested
      prochelators lead to cell-cycle arrest at the G1/S interface and induction of
      apoptosis. Notably, although hemoglobin-synthesizing blood cells have the highest
      iron need in the human body, no significant impact on hemoglobin production was
      observed in the MEL (murine erythroleukemia) model of differentiating erythroid
      cells. This study provides new information on the intracellular effects of
      disulfide-based prochelators and indicates aroylhydrazone (AH1-S)2 as a promising
      prototype of a new class of antiproliferative prochelator systems.

PMID- 29324294
TI  - Microbial community of a gasworks aquifer and identification of nitrate-reducing
      Azoarcus and Georgfuchsia as key players in BTEX degradation.
AB  - We analyzed a coal tar polluted aquifer of a former gasworks site in Thuringia
      (Germany) for the presence and function of aromatic compound-degrading bacteria
      (ACDB) by 16S rRNA Illumina sequencing, bamA clone library sequencing and
      cultivation attempts. The relative abundance of ACDB was highest close to the
      source of contamination. Up to 44% of total 16S rRNA sequences were affiliated to
      ACDB including genera such as Azoarcus, Georgfuchsia, Rhodoferax, Sulfuritalea
      (all Betaproteobacteria) and Pelotomaculum (Firmicutes). Sequencing of bamA, a
      functional gene marker for the anaerobic benzoyl-CoA pathway, allowed further
      insights into electron-accepting processes in the aquifer: bamA sequences of
      mainly nitrate-reducing Betaproteobacteria were abundant in all groundwater
      samples, whereas an additional sulfate-reducing and/or fermenting microbial
      community (Deltaproteobacteria, Firmicutes) was restricted to a highly
      contaminated, sulfate-depleted groundwater sampling well. By conducting growth
      experiments with groundwater as inoculum and nitrate as electron acceptor,
      organisms related to Azoarcus spp. were identified as key players in the
      degradation of toluene and ethylbenzene. An organism highly related to
      Georgfuchsia toluolica G5G6 was enriched with p-xylene, a particularly
      recalcitrant compound. The anaerobic degradation of p-xylene requires a metabolic
      trait that was not described for members of the genus Georgfuchsia before. In
      line with this, we were able to identify a putative 4-methylbenzoyl-CoA reductase
      gene cluster in the respective enrichment culture, which is possibly involved in
      the anaerobic degradation of p-xylene.

PMID- 29324295
TI  - Analytical determination of the reducing and stabilization agents present in
      different Zostera noltii extracts used for the biosynthesis of gold
      nanoparticles.
AB  - The objective of this work was to ascertain the nature of the components
      responsible for the reducing and stabilizing properties of Zostera noltii
      extracts that lead to gold nanoparticle formation using chemical techniques of
      analysis. In order to achieve this aim, we try the synthesis of AuNPs with three
      different extracts from plants collected in the Bay of Cadiz (Spain). The n
      butanol extract produced the best results. Taking this into account, four
      fractions were isolated by Sephadex LH-20 column chromatography from this extract
      and we studied their activity. The chemical study of these fractions led to the
      isolation of several flavone sulfates and these were identified as the species'
      responsible for the formation and stabilization of the AuNPs. Flavone sulfates
      were purified by high performance liquid chromatography and the structures were
      established by means of spectroscopic methods nuclear magnetic resonance and mass
      spectroscopy. AuNPs have an average lifetime of about 16weeks. Additionally, the
      morphology and crystalline phase of the gold nanoparticles were characterized by
      transmission electron microscopy. The composition of the nanoparticles was
      evaluated by electron diffraction and energy dispersive X-ray spectroscopy. An
      88% of the gold nanoparticles has a diameter in the range 20-35nm, with an
      average size of 26+/-2nm.

PMID- 29324297
TI  - Longitudinal joint loading in patients before and up to one year after unilateral
      total hip arthroplasty.
AB  - Abnormal kinematics and kinetics have been reported in hip osteoarthritis (OA)
      patients before and after total hip arthroplasty (THA). These changes can affect
      the loading of the ipsilateral hip, as well as the contralateral hip and knee
      joint. As it is not clear how hip and knee loading evolves in THA patients during
      the first year after surgery, the goal of this study is to define how joint
      loading changes in patients before and at three evaluation times after THA
      surgery. Musculoskeletal modelling in combination with gait analysis data was
      used to calculate hip and knee contact forces in 14 patients before and 3-, 6-
      and 12-months after unilateral THA, as well as in 18 healthy controls. Results
      showed that bilateral hip and knee loading were decreased compared to controls,
      both before and after THA surgery. Loading symmetry was altered compared to
      controls at 3-months post-surgery for the hip and at all evaluation times, except
      for 6-months post-surgery, for the knee, with ipsilateral joint loading decreased
      compared to the contralateral side. To conclude, 12-months after THA joint
      loading was not normalized, with both hip and knee loading in patients decreased
      compared to controls. Therefore, no overloading of the ipsi- or contralateral hip
      and knee joint was found before and up to one year after unilateral THA.

PMID- 29324296
TI  - Inertial sensing of the motion speed effect on the sit-to-walk activity.
AB  - The STW execution at motion speed faster than normal most possibly enhances the
      risk for balance loss due to the increase in body segment accelerations. The
      purpose of the study was to use inertial sensing to examine the effect of motion
      speed on the STW segmental kinematics and its temporal events. Eighteen young men
      (20.7 +/- 2.0 years) performed STW trials at preferred (PS) and fast (FS) motion
      speed. Data were collected with Xsens inertial sensors positioned at the trunk,
      thigh, shank, and foot segments. The maximum segmental values of angular
      displacement, angular velocity and linear acceleration, the duration of total STW
      (ttotal), the absolute and relative (% ttotal) phase duration (Flexion,
      Transition, Extension, Walking) and, the absolute and relative time taken to
      reach each maximum value were determined. In FS, ttotal and the absolute phase
      duration (except for Transition), were all significantly shorter (p = 0.000). The
      relative phase duration was not altered (p > 0.05), except for the Extension
      shortening (p = 0.001). The maximum angular displacement was altered only for the
      thigh (decreased, p = 0.038) and shank (increased, p = 0.004). Maximum angular
      velocities and linear accelerations were all significantly increased (p = 0.000
      for all). The absolute time to reach the maximum values shortened in FS (p <=
      0.05), while, the relative times were not altered (p > 0.05), except for the
      delayed trunk maximum angular displacement (p = 0.039). Inertial sensing appears
      to identify the motion speed effect on STW segmental kinematics and their
      temporal events in healthy young men. The results of the study may contribute
      improving the preventive or rehabilitation interventions in persons with impaired
      postural control.

PMID- 29324298
TI  - Calibration of raw accelerometer data to measure physical activity: A systematic
      review.
AB  - Most of calibration studies based on accelerometry were developed using count
      based analyses. In contrast, calibration studies based on raw acceleration
      signals are relatively recent and their evidences are incipient. The aim of the
      current study was to systematically review the literature in order to summarize
      methodological characteristics and results from raw data calibration studies. The
      review was conducted up to May 2017 using four databases: PubMed, Scopus,
      SPORTDiscus and Web of Science. Methodological quality of the included studies
      was evaluated using the Landis and Koch's guidelines. Initially, 1669 titles were
      identified and, after assessing titles, abstracts and full-articles, 20 studies
      were included. All studies were conducted in high-income countries, most of them
      with relatively small samples and specific population groups. Physical activity
      protocols were different among studies and the indirect calorimetry was the
      criterion measure mostly used. High mean values of sensitivity, specificity and
      accuracy from the intensity thresholds of cut-point-based studies were observed
      (93.7%, 91.9% and 95.8%, respectively). The most frequent statistical approach
      applied was machine learning-based modelling, in which the mean coefficient of
      determination was 0.70 to predict physical activity energy expenditure. Regarding
      the recognition of physical activity types, the mean values of accuracy for
      sedentary, household and locomotive activities were 82.9%, 55.4% and 89.7%,
      respectively. In conclusion, considering the construct of physical activity that
      each approach assesses, linear regression, machine-learning and cut-point-based
      approaches presented promising validity parameters.

PMID- 29324300
TI  - Hippocampal insulin resistance links maternal obesity with impaired neuronal
      plasticity in adult offspring.
AB  - OBJECTIVE: Maternal obesity and a disturbed metabolic environment during
      pregnancy and lactation have been shown to result in many long-term health
      consequences for the offspring. Among them, impairments in neurocognitive
      development and performance belong to the most dreaded ones. So far, very few
      mechanistic approaches have aimed to determine the responsible molecular events.
      METHODS: In a mouse model of maternal diet-induced obesity and perinatal
      hyperinsulinemia, we assessed adult offspring's hippocampal insulin signaling as
      well as concurrent effects on markers of hippocampal neurogenesis, synaptic
      plasticity and function using western blotting and immunohistochemistry. In
      search for a potential link between neuronal insulin resistance and hippocampal
      plasticity, we additionally quantified protein expression of key molecules of
      synaptic plasticity in an in vitro model of acute neuronal insulin resistance.
      RESULTS: Maternal obesity and perinatal hyperinsulinemia result in adult
      hippocampal insulin resistance with subsequently reduced hippocampal mTor
      signaling and altered expression of markers of neurogenesis (doublecortin),
      synaptic plasticity (FoxO1, pSynapsin) and function (vGlut, vGAT) in the
      offspring. The observed effects are independent of the offspring's adult
      metabolic phenotype and can be associated with multiple previously reported
      behavioral abnormalities. Additionally, we demonstrate that induction of insulin
      resistance in cultured hippocampal neurons reduces mTor signaling, doublecortin
      and vGAT protein expression. CONCLUSIONS: Hippocampal insulin resistance might
      play a key role in mediating the long-term effects of maternal obesity and
      perinatal hyperinsulinemia on hippocampal plasticity and the offspring's
      neurocognitive outcome.

PMID- 29324299
TI  - Boys with conduct problems and callous-unemotional traits: Neural response to
      reward and punishment and associations with treatment response.
AB  - Abnormalities in reward and punishment processing are implicated in the
      development of conduct problems (CP), particularly among youth with callous
      unemotional (CU) traits. However, no studies have examined whether CP children
      with high versus low CU traits exhibit differences in the neural response to
      reward and punishment. A clinic-referred sample of CP boys with high versus low
      CU traits (ages 8-11; n = 37) and healthy controls (HC; n = 27) completed a fMRI
      task assessing reward and punishment processing. CP boys also completed a
      randomized control trial examining the effectiveness of an empirically-supported
      intervention (i.e., Stop-Now-And-Plan; SNAP). Primary analyses examined pre
      treatment differences in neural activation to reward and punishment, and
      exploratory analyses assessed whether these differences predicted treatment
      outcome. Results demonstrated associations between CP and reduced amygdala
      activation to punishment independent of age, race, IQ and co-occurring ADHD and
      internalizing symptoms. CU traits were not associated with reward or punishment
      processing after accounting for covariates and no differences were found between
      CP boys with high versus low CU traits. While boys assigned to SNAP showed a
      greater reduction in CP, differences in neural activation were not associated
      with treatment response. Findings suggest that reduced sensitivity to punishment
      is associated with early-onset CP in boys regardless of the level of CU traits.

PMID- 29324301
TI  - Depression and fatigue in multiple sclerosis: Relation to exposure to violence
      and cerebrospinal fluid immunomarkers.
AB  - Multiple sclerosis (MS) is a neuroinflammatory condition characterized by chronic
      dysregulation of immune responses leading to repeated episodes of inflammation in
      the central nervous system. Depression and fatigue are common among MS patients,
      even in early disease phases, and the disease course can be negatively affected
      by stressful events. IL-6 and IL-8 have been associated with depression and
      stressful life events in non-MS patients. The aim of this study was to examine
      the relationships between depression, fatigue, and exposure to violence, with IL
      6 and IL-8 levels in the cerebrospinal fluid (CSF) of MS patients. Levels of IL-6
      and -8 were analyzed in the CSF of 47 patients with relapsing-remitting MS.
      Correlations between IL-6 and IL-8 levels and self-rated depression and fatigue
      symptoms, as well as clinician-rated history of being exposed to interpersonal
      violence, were analyzed with correction for age, sex and MS disability status. IL
      6 correlated significantly (p < 0.05) with depressive symptoms (adjusted
      Spearman's rho = 0.39), fatigue (rho = 0.39), and exposure to violence in adult
      life (rho = 0.35). Depression correlated with both fatigue and being exposed to
      violence. Associations were not present among patients exposed to disease
      modifying drugs. In exploratory analyses, the relationship between exposure to
      violence and IL-6 was non-significant when controlled for depression. Further
      research should focus on replication of these results, as well as exploring the
      impact of stressful life events on immune regulation and the clinical
      characteristics and prognosis of MS patients.

PMID- 29324302
TI  - Addressing the paradox of increasing mastectomy rates in an era of de-escalation
      of therapy: Communication strategies.
AB  - Breast conservation therapy (BCT) was established as the preferred modality of
      surgical treatment for early stage breast cancer in the early 1990's. Yet, rising
      mastectomy rates have been observed over the last decade. This increase is a
      cause for concern as recent large population-based studies have consistently
      reported improved breast cancer-specific survival and local control rates with
      BCT, in comparison with mastectomy. There is a pressing need to formulate
      strategies to effectively inform both patients and practitioners about current
      data, in the hope of reversing rising mastectomy rates to optimise survival
      outcomes. Based on the available evidence relating to the motivators for a
      mastectomy, a format for presenting data to bridge the existing knowledge deficit
      for effective patient counselling is proposed in this review.

PMID- 29324303
TI  - First-line vs second-line fulvestrant for hormone receptor-positive advanced
      breast cancer: A post-hoc analysis of the CONFIRM study.
AB  - OBJECTIVES: The double-blind, phase III CONFIRM study (NCT00099437) evaluated
      fulvestrant 500 mg vs fulvestrant 250 mg in postmenopausal women with hormone
      receptor-positive locally advanced/metastatic breast cancer (LA/MBC). This post
      hoc analysis investigated the efficacy and safety of fulvestrant given either
      first-line or second-line for advanced disease. MATERIALS & METHODS: Progression
      free survival (PFS) and overall survival (OS) with fulvestrant 500 mg vs
      fulvestrant 250 mg was evaluated using unadjusted log-rank tests in patients
      treated in the first- (progression during or within 12 months after completing
      adjuvant endocrine therapy; n = 387) and second-line (following endocrine therapy
      for LA/MBC; n = 343) settings. RESULTS: First-line fulvestrant 500 mg
      significantly prolonged PFS vs fulvestrant 250 mg (median PFS 5.6 vs 4.2 months;
      hazard ratio [HR] 0.80; 95% confidence interval [CI] 0.64-1.00; p = .047). Median
      PFS was numerically greater with second-line fulvestrant 500 mg vs fulvestrant
      250 mg (7.9 vs 6.3 months; HR 0.80; 95% CI 0.64-1.02; p = .068). At data cut-off
      (75.5% maturity), median OS with first-line fulvestrant 500 mg was 23.2 vs 22.1
      months with fulvestrant 250 mg (HR 0.87; 95% CI 0.70-1.10; p = .251), and 29.2 vs
      22.8 months, respectively, in the second-line (HR 0.75; 95% CI 0.58-0.96; p =
      .020). The safety profile was broadly comparable between dose groups and across
      treatment lines, and consistent with the overall patient population. CONCLUSION:
      The superiority of fulvestrant 500 mg over fulvestrant 250 mg in patients with
      LA/MBC in CONFIRM was consistent in both the first- and second-line settings for
      PFS, and numerically greater in both settings for OS.

PMID- 29324304
TI  - Injectable polypeptide hydrogel for dual-delivery of antigen and TLR3 agonist to
      modulate dendritic cells in vivo and enhance potent cytotoxic T-lymphocyte
      response against melanoma.
AB  - Transplantation of immune cells manipulated in vitro to dictate immune responses
      in the body is promising in cancer immunotherapy. However, this approach suffers
      from low cell survival after administration, insufficient cell homing to lymph
      nodes, and off-target. Here we demonstrate an injectable and self-assembled
      poly(l-valine) hydrogel as the delivery carrier of cargoes including antigen and
      immunopotentiator for DCs modulation. Our results indicate the vaccine
      formulation composed of tumor cell lysates (TCL), TLR3 agonist, poly(I:C) and
      polypeptide hydrogel can robustly recruit, activate and mature DCs in vitro and
      in vivo by sustained release of TCL and poly(I:C). Hydrogel as the delivery
      system significantly improves antigen persistence at the injection site and
      antigen drainage to lymph nodes. Strikingly, subcutaneous injection of hydrogel
      based vaccine formulations in melanoma-bearing mice elicits good antitumor
      efficiency by evoking strong cytotoxic T-lymphocyte immune response. Hydrogel
      vaccine significantly promotes the production of CD8+ T cells in draining lymph
      nodes and tumor infiltrating T-lymphocytes. These findings suggest that in vivo
      program of DCs by injectable polypeptide hydrogel encapsulated with antigen and
      immunopentiator is able to direct immune responses against cancer. Our study also
      implies that such a hydrogel may serve as a multifunctional delivery platform of
      vaccines.

PMID- 29324306
TI  - Mechanically resilient injectable scaffolds for intramuscular stem cell delivery
      and cytokine release.
AB  - A promising strategy for treating peripheral ischemia involves the delivery of
      stem cells to promote angiogenesis through paracrine signaling. Treatment success
      depends on cell localization, retention, and survival within the mechanically
      dynamic intramuscular (IM) environment. Herein we describe an injectable, in situ
      gelling hydrogel for the IM delivery of adipose-derived stem/stromal cells
      (ASCs), specifically designed to withstand the dynamic loading conditions of the
      lower limb and facilitate cytokine release from encapsulated cells. Copolymers of
      poly(trimethylene carbonate)-b-poly(ethylene glycol)-b-poly(trimethylene
      carbonate) diacrylate were used to modulate the properties of methacrylated
      glycol chitosan hydrogels crosslinked by thermally-initiated polymerization using
      ammonium persulfate and N,N,N',N'-tetramethylethylenediamine. The scaffolds had
      an ultimate compressive strain over 75% and maintained mechanical properties
      during compressive fatigue testing at physiological levels. Rapid crosslinking
      (<3 min) was achieved at low initiator concentration (5 mM). Following injection
      and crosslinking within the scaffolds, human ASCs demonstrated high viability
      (>90%) over two weeks in culture under both normoxia and hypoxia. Release of
      angiogenic and chemotactic cytokines was enhanced from encapsulated cells under
      sustained hypoxia, in comparison to normoxic and tissue culture polystyrene
      controls. When delivered by IM injection in a mouse model of hindlimb ischemia,
      human ASCs were well retained in the scaffold over 28 days and significantly
      increased the IM vascular density compared to untreated controls.

PMID- 29324307
TI  - Integrin alpha5beta1 suppresses rBMSCs anoikis and promotes nitric oxide
      production.
AB  - BACKGROUND: Cell based therapy has been heralded as a novel, promising
      therapeutic strategy for cardiovascular diseases including pulmonary arterial
      hypertension (PAH). However, the low survival rate after transplantation due to
      cell death via anoikis is a major obstacle in stem cell therapy. Cells adhesion
      via Integrin alpha5beta1 (ITGA5B1) has a tendency to exert higher maximum forces.
      The present study aimed to evaluate the potential protective effect of ITGA5B1 on
      rat bone marrow mesenchymal stem cells (rBMSCs) from anoikis. METHODS:
      Mononuclear cells were isolated by density gradient centrifugation with Ficoll,
      and rBMSCs cell surface markers were evaluated by flow cytometry. Osteogenic and
      adipocyte differentiation was determined by Alizarin Red S and Oil Red O staining
      respectively. The expression of Integrin A5 (ITGA5), Integrin B1 (ITGB1), eNOS
      and actived-caspase-3 mRNA or protein was confirmed by qPCR and western-blot.
      Cell adhesion, cell viability, anoikis and the migration of rBMSCs were also
      evaluated. Nitric oxide (NO) production was detected by the greiss assay.
      RESULTS: Co-infected with Integrin A5 and B1 lentivirus to rBMSCs increased ITGA5
      and ITGB1 mRNA and protein expression. ITGA5B1 enhanced the cell adhesion, cell
      viability, cell migration and NO production but reduced the cell anoikis in
      rBMSCs/ITGA5B1 groups. CONCLUSION: Transduction of rat rBMSCs with ITGA5B1
      lentivirus could prevent cell anoikis and increase NO production.

PMID- 29324305
TI  - Caveolin-mediated endocytosis of the Chlamydia M278 outer membrane peptide
      encapsulated in poly(lactic acid)-Poly(ethylene glycol) nanoparticles by mouse
      primary dendritic cells enhances specific immune effectors mediated by MHC class
      II and CD4+ T cells.
AB  - We previously developed a Chlamydia trachomatis nanovaccine (PPM) by
      encapsulating a chlamydial M278 peptide within poly(lactic acid)-poly(ethylene
      glycol) biodegradable nanoparticles that immunopotentiated Chlamydia-specific
      immune effector responses in mice. Herein, we investigated the mechanistic
      interactions of PPM with mouse bone marrow-derived dendritic cells (DCs) for its
      uptake, trafficking, and T cell activation. Our results reveal that PPM triggered
      enhanced expression of effector cytokines and chemokines, surface activation
      markers (Cd1d2, Fcgr1), pathogen-sensing receptors (TLR2, Nod1), co-stimulatory
      (CD40, CD80, CD86) and MHC class I and II molecules. Co-culturing of PPM-primed
      DCs with T cells from C. muridarum vaccinated mice yielded an increase in
      Chlamydia-specific immune effector responses including CD3+ lymphoproliferation,
      CD3+CD4+ IFN-gamma-secreting cells along with CD3+CD4+ memory (CD44high and
      CD62Lhigh) and effector (CD44high and CD62Llow) phenotypes. Intracellular
      trafficking analyses revealed an intense expression and colocalization of PPM
      predominantly in endosomes. PPM also upregulated the transcriptional and protein
      expression of the endocytic mediator, caveolin-1 in DCs. More importantly, the
      specific inhibition of caveolin-1 led to decreased expression of PPM-induced
      cytokines and co-stimulatory molecules. Our investigation shows that PPM provided
      enhancement of uptake, probably by exploiting the caveolin-mediated endocytosis
      pathway, endosomal processing, and MHC II presentation to immunopotentiate
      Chlamydia-specific immune effector responses mediated by CD4+ T cells.

PMID- 29324308
TI  - Antacids' side effect hyperuricaemia could be alleviated by long-term aerobic
      exercise via accelerating ATP turnover rate.
AB  - Hyperuricemia is the term for an abnormally high serum uric acid level. Many
      factors contribute to hyperuricemia, however no definite correlation between
      proton pump inhibitors (PPIs) and hyperuricemia has been reported before.
      Physical exercise also decreases serum uric acid levels. However, the detailed
      biochemical-regulatory mechanisms remain unknown. Here we found that adenylate
      deaminase activities are much higher in hyperuricemia patients than in the
      healthy people. Therefore, the patients have higher levels of adenosine
      metabolites hypoxanthine and uric acid. Acid-inhibitory drugs (antacids)
      significantly increased serum uric acid level and may lead to gout in the
      hyperuricemia patient. Long-term aerobic exercise significantly increased serum
      phosphorus and decreased serum ATP and its metabolites, and therefore decreased
      serum uric acid. Antacids slow down the ATP turnover rate and result in serum
      uric acid elevation subsequently. While the long-term aerobic exercise decreases
      serum uric acid levels by accelerating ATP turnover rate. The results imply that
      long-term aerobic exercise may be a useful strategy to prevent and treat
      hyperuricaemia.

PMID- 29324309
TI  - The promising future of ventricular restraint therapy for the management of end
      stage heart failure.
AB  - Complicated pathophysiological syndrome associated with irregular functioning of
      the heart leading to insufficient blood supply to the organs is linked to
      congestive heart failure (CHF) which is the leading cause of death in developed
      countries. Numerous factors can add to heart failure (HF) pathogenesis, including
      myocardial infarction (MI), genetic factors, coronary artery disease (CAD),
      ischemia or hypertension. Presently, most of the therapies against CHF cause
      modest symptom relief but incapable of giving significant recovery for long-term
      survival outcomes. Unfortunately, there is no effective treatment of HF except
      cardiac transplantation but genetic variations, tissue mismatch, differences in
      certain immune response and socioeconomic crisis are some major concern with
      cardiac transplantation, suggested an alternate bridge to transplant (BTT) or
      destination therapies (DT). Ventricular restraint therapy (VRT) is a promising,
      non-transplant surgical treatment wherein the overall goal is to wrap the dilated
      heart with prosthetic material to mechanically restrain the heart at end
      diastole, stop extra remodeling, and thereby ultimately improve patient symptoms,
      ventricular function and survival. Ventricular restraint devices (VRDs) are
      developed to treat end-stage HF and BTT, including the CorCap cardiac support
      device (CSD) (CSD; Acorn Cardiovascular Inc, St Paul, Minn), Paracor HeartNet
      (Paracor Medical, Sunnyvale, Calif), QVR (Polyzen Inc, Apex, NC) and ASD (ASD, X.
      Zhou). An overview of 4 restraint devices, with their precise advantages and
      disadvantages, will be presented. The accessible peer-reviewed literature
      summarized with an important considerations on the mechanism of restraint therapy
      and how this acquaintance can be accustomed to optimize and improve its
      effectiveness.

PMID- 29324310
TI  - 25-Hydroxyl-protopanaxatriol protects against H2O2-induced H9c2 cardiomyocytes
      injury via PI3K/Akt pathway and apoptotic protein down-regulation.
AB  - Oxidative stress injury and apoptosis are the main mechanisms of myocardial
      ischemia-reperfusion injury (MI/RI). Compounds with anti-oxidant properties can
      treat MI/RI. Therefore, identification of natural antioxidants such as herbs or
      botanical drugs is an ideal strategy to develop safe and effective anti-MI/RI
      drugs. Cardioprotective effects of Ginseng are well documented and are
      attributable to its anti-oxidant, anti-inflammatory, anti-tumorigenic, anti
      arrhythmic, anti-ischemic properties. Ginseng monomer 20(r)-dammarane -3 beta,6
      alpha,12 beta,20,25-pentol(25-hydroxyl-Protopanaxatriol,25-OH-PPT), a novel
      compound, which belongs to panaxatriol category, is extracted from the leaves and
      stem of ginseng. It was first investigated for its anti-tumorigenic properties.
      In this study, we explored whether 25-OH-PTT plays a role in antioxidant stress
      injury and anti-apoptosis in cardiomyocytes. We also explored the mechanisms in
      order to provide a theoretical basis to develop 25-OH-PPT as a new drug for
      treatment of MI/RI. First, we used H2O2 to induce H9c2 cardiomyocytes in vitro
      resulting in an oxidative stress injury model and pretreated with 25-OH-PPT.
      Secondly, we examined the viability of H9c2 cells by MTT assay, the reactive
      oxygen species (ROS) content and mitochondrial membrane potential by flow
      cytometry as well as cell apoptosis by flow cytometry Annexin-FITC/PI and Hoechst
      33258 staining. Furthermore, we pretreated H9c2 cells with PI3K inhibitor,
      LY294002, and observed the above phenomenon. Lastly, we examined the expressions
      of proteins related to the PI3K/Akt signaling pathway and the apoptotic proteins.
      We found that 25-OH-PPT can protect H9c2 cells against H2O2-induced injury,
      decrease apoptosis of H9c2 cells and ROS generation, and increase the
      mitochondrial membrane potential. It can also upregulate the protein expressions
      of p-Akt, p-eNOS, and Bcl-2 and down-regulate apoptotic proteins Bax and Caspase
      3. Our results indicate that 25-OH-PPT inhibits H2O2-induced H9c2 cardiomyocytes
      injury through PI3K/Akt pathway. It may become a potential safe and effective
      traditional Chinese medicine monomer for treatment of MI/RI.

PMID- 29324311
TI  - Corilagin, a promising medicinal herbal agent.
AB  - Corilagin, a gallotannin, is one of the major active components of many
      ethnopharmacological plants. It was isolated from Caesalpinia coriaria (Jacq.)
      Willd. (dividivi) by Schmidt in 1951 for the first time. In the past few decades,
      corilagin was reported to exhibit anti-tumor, anti-inflammatory and
      hepatoprotective activities, etc. However, little attention was paid to its
      pharmacological properties due to the complicated and inefficient extract method.
      In recent years, with the development of extraction technology corilagin was much
      easier to obtain than before. Thus, people return to pay attention to its anti
      tumor, hepatoprotective, and anti-inflammatory activities, particularly as an
      anti-tumor agent candidate. Our research team had focused on the distribution,
      preparation and anti-tumor activity of corilagin since 2005. We found corilagin
      showed good anti-tumor activity on hepatocellular carcinoma and ovarian cancer.
      What's more, corilagin showed a low level of toxicity toward normal cells and
      tissues. Due to the extensive attention that corilagin has received, we present a
      systematic review of the pharmacological effects of corilagin. In this review, we
      summarized all the pharmacological effects of corilagin with a focus on the
      molecular mechanism of anti-tumor activity and show you how corilagin affected
      the signaling pathways of tumor cells as well as its physicochemical properties,
      distribution and preparation methods.

PMID- 29324312
TI  - The hypoxia-responsive long non-coding RNAs may impact on the tumor biology and
      subsequent management of breast cancer.
AB  - Long non-coding RNAs (lncRNAs) are DNA transcripts longer than 200 nucleotides
      without protein-coding potential. As they are key regulators of gene expression
      at chromatic, transcriptional and posttranscriptional level, they play important
      role in various biological and pathological processes. Dysregulation of lncRNAs
      has been observed in several diseases including cancer. Breast cancer is
      heterogeneous disease with many molecular subtypes specific in different
      prognosis and treatment responses. Hypoxia, a common micro-environmental feature
      of rapidly growing tumour is associated with metastases, recurrences and
      resistance to therapy. Aberrant expression of hypoxia related lncRNAs
      significantly correlates with poor outcomes in cancer patients, as the lncRNAs
      play an important regulatory role in the breast cancer-cell survival. Thus, a
      better understanding of lncRNAs role in the hypoxic conditions of breast cancer
      is crucial for precise understanding of the tumorigenesis, disease features and
      poor clinical outcome, especially in highly aggressive breast cancer subtypes
      (HER2-positive and triple-negative types). Moreover, lncRNAs may represent tumour
      marker predicting prognosis and therapeutic targets improving precise and
      personalized therapy for better patient's survival. In this review, we summarize
      the recent information on lncRNAs in breast cancer with special focus on the
      hypoxia-responsive lncRNAs and their potential impact on the prognosis, therapy
      algorithms and individual outcomes. Presented data helps in better understanding
      of the specific mechanisms predicting new therapeutic agents and strategies for
      the pharmacological intervention.

PMID- 29324313
TI  - Knockdown of TRIM37 suppresses the proliferation, migration and invasion of
      glioma cells through the inactivation of PI3K/Akt signaling pathway.
AB  - Tripartite motif 37 (TRIM37), a member of the TRIM protein family, was involved
      in the tumorigenesis of several types of cancer. However, the expression pattern
      and role of TRIM37 in glioma remain unclear. Therefore, the aim of the present
      study was to investigate the role of TRIM37 in glioma, and to determine the
      molecular mechanisms. Our results demonstrated that TRIM37 was highly expressed
      in human glioma tissues and cell liens. Additionally, knockdown of TRIM37
      dramatically inhibited the proliferation, migration/invasion, and the epithelial
      mesenchymal transition (EMT) phenotype in glioma cells. Furthermore, knockdown of
      TRIM37 significantly reduced the levels of phosphorylated PI3K and Akt in U87MG
      cells, and an activator of PI3K/Akt signaling (SC79) partly reversed the
      inhibitory effects of si-TRIM37 on glioma cell proliferation and migration. Taken
      together, our results demonstrated that TRIM37 functions as an oncogene in the
      development and progression of glioma. TRIM37 knockdown inhibited the
      proliferation and invasion of human glioma cells at least in part through the
      inactivation of PI3K/Akt signaling pathway.

PMID- 29324314
TI  - Down-regulation of miR-133a/b in patients with myocardial infarction correlates
      with the presence of ventricular fibrillation.
AB  - MicroRNAs (miRNAs) are important regulators of physiologic and pathologic
      conditions of the heart. Animal models of heart diseases have shown that miRNAs
      may contribute to the development of arrhythmias. However, little is known about
      the expression of muscle- and cardiac-specific miRNAs in patients with myocardial
      infarction (MI) who have developed ventricular fibrillation (VF). Our study
      included 47 patients who had died from myocardial infarction (MI), 23 with
      clinically proven VF and 24 without VF. Autopsy samples of infarcted tissue and
      remote myocardium were available (n = 94). Heart tissue from 8 healthy trauma
      victims was included as control. Expression of miR-1, miR-133a/b and miR-208 was
      analyzed using real-time PCR (qPCR). In patients with MI with VF, we observed
      down-regulation of miR-133a/b, and this down-regulation was even stronger 2-7
      days after MI. miR-208 was up-regulated in remote myocardium irrespective of the
      presence of VF. Deregulation of miR-1 and miR-208 was not related to the presence
      of VF. Our results suggest that down-regulation of miR-133a/b might contribute to
      the development of VF in patients with MI. However, up-regulation of miR-1 and
      miR-208 in remote myocardium might play a role in cardiac remodeling after MI, at
      least to certain degree.

PMID- 29324315
TI  - Histone demethylase KDM5A inhibits glioma cells migration and invasion by down
      regulating ZEB1.
AB  - Malignant gliomas are highly lethal cancers worldwide as tumor cells infiltrate
      to healthy brain tissue invariably. Histone demethylase KDM5A as an oncogene or
      tumor suppressor in cancer still has been controversial. KDM5A may have a
      different function in different type cancer cells. However, the specific roles of
      KDM5A in the progression of glioma remain undiscovered. In this study, we found
      that compared with primary glioma, metastasis glioma had low KDM5A levels.
      Besides, lower KDM5A levels were linked to poor survival in glioma cancer
      patients, indicating that KDM5A is a new prognostic marker for glioma cancer.
      KDM5A knockdown increases the invasive abilities of glioma cancer cells and
      changes the EMT markers. A mechanism, KDM5A suppressing the expression of ZEB1,
      and its catalytic activity is indispensable for anti-invasive function. Our study
      revealed that histone demethylase KDM5A exerts anti-invasiveness function partly
      through repressing oncogenic ZEB1 expression by mediating H3K4 demethylation. We
      also demonstrate that ZEB1 play a crucial role in KDM5A induced function. In
      summary, in this study, we showed that KDM5A has a crucial role in glioma and
      therefore may serve as a novel therapeutic target and prognostic marker in
      glioma.

PMID- 29324316
TI  - MicroRNA-145 alleviates high glucose-induced proliferation and migration of
      vascular smooth muscle cells through targeting ROCK1.
AB  - The excessive proliferation and migration of vascular smooth muscle cells (VSMCs)
      are important steps in atherosclerosis. The present study aimed to investigate
      whether the high glucose-induced changes of VSCMs are mediated by miR-145 and the
      potential molecular mechanism involved. We found that loss of miR-145 accompanied
      with increased proliferation and migration was observed in cultured human VSMCs
      exposed to high glucose. Exogenous overexpression of miR-145 effectively
      suppressed the high glucose-induced excessive proliferation and migration of
      VSMCs. Furthermore, we identified ROCK1 as a downstream target gene product of
      miR-145, and ROCK1 partially rescues the effects of miR-145 on high glucose
      induced VSMC proliferation and migration. Taken together, our results suggested a
      protective role of miR-145 in high glucose-treated VSMCs by suppressing ROCK1,
      which might provide a therapeutic target for diabetic atherosclerosis.

PMID- 29324317
TI  - TINCR suppresses proliferation and invasion through regulating miR-544a/FBXW7
      axis in lung cancer.
AB  - BACKGROUND: Long noncoding RNAs (LncRNAs) play critical roles in multiple
      biological processes implicated in the development and progression of cancers.
      Terminal differentiation-induced lncRNA (TINCR) has been demonstrated to be
      associated with the carcinogenesis of several cancers. However, little is known
      about the function and mechanism of TINCR in lung cancer. METHODS: qRT-PCR was
      performed to measure the expression of TINCR, miR-544a or FBXW7 mRNA in lung
      cancer tissues or cells. FBXW7 protein level was detected via western blot
      analysis. Cell Counting Kit-8 (CCK-8) and transwell invasion analysis were used
      to assess the proliferative and invasive ability of lung cancer cells.
      Bioinformatic softwares, luciferase reporter assay, and RNA immunoprecipitation
      (RIP) were employed to explore the relationship between TINCR, miR-544a and
      FBXW7. RESULTS: TINCR expression was downregulated while miR-544a expression was
      upregulated in lung cancer tissues and cells. TINCR overexpression suppressed
      proliferation and invasion in lung cancer cells. Moreover, TINCR was confirmed as
      a molecular sponge of miR-544a. We further validated that miR-544a facilitated
      proliferation and invasion, and miR-544a could reverse TINCR-mediated anti
      proliferation and anti-invasion effect in lung cancer cells. TINCR acted as a
      competing endogenous RNA (ceRNA) to sequester miR-544a from its target gene
      FBXW7. Finally, FBXW7 suppressed proliferation and invasion, and FBXW7 knockdown
      abolished the inhibition of TINCR on proliferation and invasion in lung cancer
      cells. CONCLUSION: TINCR suppressed proliferation and invasion through regulating
      miR-544a/FBXW7 axis in lung cancer, indicating that it might be a potential
      target for the therapy of lung cancer.

PMID- 29324318
TI  - A feasibility study of a multidimensional breastfeeding-support intervention in
      Ireland.
AB  - BACKGROUND: Breastfeeding is the optimum mode of infant feeding. Despite this,
      most global populations do not achieve the World Health Organisation's
      recommendation of exclusive breast milk for the first 6 months of life. Irish
      breastfeeding rates are among the lowest in Europe, necessitating a well-designed
      breastfeeding-support intervention. AIM: To evaluate the feasibility and
      acceptability of a multidimensional breastfeeding intervention in a rural and an
      urban maternity setting in Ireland. DESIGN: A feasibility study of a
      breastfeeding-support intervention. SETTING: Participants were recruited from The
      National Maternity Hospital (Dublin, urban) and Wexford General Hospital
      (Wexford, rural). Questionnaires were completed antenatally, at 6 weeks
      postpartum and at 3 months postpartum to assess acceptability of the intervention
      and determine breastfeeding status. PARTICIPANTS: Pregnant women were recruited
      in the 3rd trimester, alongside a support partner. INTERVENTION: The intervention
      consisted of an antenatal class (including the physiology and practical
      approaches to breastfeeding), a one-to-one breastfeeding consultation with a
      lactation consultant after birth, access to a breastfeeding helpline, online
      resources, and a postnatal breastfeeding support group which included a one-to
      one consultation with the lactation consultant. RESULTS: One hundred women from
      The National Maternity Hospital, Dublin and 27 women from Wexford General
      Hospital were recruited. The antenatal class was attended by 77 women in Dublin
      and 23 in Wexford; thus, 100 women participated in the intervention. Seventy-six
      women had a one-to-one postnatal consultation with a lactation consultant in
      Dublin and 23 in Wexford. Fifty and 45 women in Dublin, and 15 and 15 in Wexford
      responded to the 6-week and 3-month questionnaires, respectively. At 3 months
      postpartum, 70% of respondents from Dublin and 60% from Wexford were
      breastfeeding. Mothers perceived the one-to-one consultation with the lactation
      consultant during postnatal hospitalization as the most helpful part of the
      intervention. Inclusion of a support partner was universally viewed positively as
      a means to support the mother's decision to initiate and continue breastfeeding.
      CONCLUSION: This multidimensional intervention is well-accepted and feasible to
      carry out within an Irish cohort, in both urban and rural areas. Data from this
      feasibility study will be used to design a randomized controlled trial of a
      breastfeeding-support intervention.

PMID- 29324319
TI  - Dental age estimation employing CBCT scans enhanced with Mimics software:
      Comparison of two different approaches using pulp/tooth volumetric analysis.
AB  - The methods of dental age estimation and identification of unknown deceased
      individuals are evolving with the introduction of advanced innovative imaging
      technologies in forensic investigations. However, assessing small structures like
      root canal volumes can be challenging in spite of using highly advanced
      technology. The aim of the study was to investigate which amongst the two methods
      of volumetric analysis of maxillary central incisors displayed higher strength of
      correlation between chronological age and pulp/tooth volume ratio for Malaysian
      adults. Volumetric analysis of pulp cavity/tooth ratio was employed in Method 1
      and pulp chamber/crown ratio (up to cemento-enamel junction) was analysed in
      Method 2. The images were acquired employing CBCT scans and enhanced by
      manipulating them with the Mimics software. These scans belonged to 56 males and
      54 females and their ages ranged from 16 to 65 years. Pearson correlation and
      regression analysis indicated that both methods used for volumetric measurements
      had strong correlation between chronological age and pulp/tooth volume ratio.
      However, Method 2 gave higher coefficient of determination value (R2 = 0.78) when
      compared to Method 1 (R2 = 0.64). Moreover, manipulation in Method 2 was less
      time consuming and revealed higher inter-examiner reliability (0.982) as no
      manual intervention during 'multiple slice editing phase' of the software was
      required. In conclusion, this study showed that volumetric analysis of pulp
      cavity/tooth ratio is a valuable gender independent technique and the Method 2
      regression equation should be recommended for dental age estimation.

PMID- 29324320
TI  - First survey of forensically important insects from human corpses in Shiraz,
      Iran.
AB  - The presence of insects on human cadavers has potential judicial value in
      medicolegal cases. This research emphasized the important role of insects in
      postmortem decomposition. It was conducted to investigate the composition and
      abundance of insects from human corpses during autopsies in legal medicine. It
      was implemented in the city of Shiraz, south Iran. Insects associated with human
      corpses were carefully collected and put into labelled vials. They were then
      identified using valid taxonomic keys. Fifteen outdoor (67%) and indoor
      discovered cadavers were examined. All but one was covered at the time of
      discovery. From these several species of entomofauna played important roles in
      the minimum postmortem interval (minPMI) estimate. Insects included the orders of
      Diptera and Coleoptera. Overall, 14 different species of arthropods were
      identified. Within Diptera, 2 families of Sarcophagidae and Calliphoridae were
      present in 73% of the cases with Calliphora vicina Robineau-Desvoidy and
      Chrysomya albiceps Wiedemann accounting for about half of the cases. The latter
      family members, Calliphoridae, were more frequently (52%) collected in autumn and
      winter. Only 4/15 outdoor cadavers had beetles. Four species of Coleopterans;
      namely Dermestes frischii Kugelann, Nitidula flavomaculata Rossi, Creophilus
      maxillosus Linnaeus and Saprinus chalcites Illiger; were recorded for the first
      time from 3 corpses in Iran. The presence and diversity of different insects on
      human corpses could contribute to the advancement of forensic entomology
      knowledge and the refined estimates of minPMI in medicolegal cases.

PMID- 29324321
TI  - Injuries sustained in falling fatalities in relation to different distances of
      falls.
AB  - BACKGROUND: Falling from a distance is an important issue worldwide, which
      happens in different ages, genders and circumstances. It is usually not
      considered a medicolegal case in many countries hence no autopsy is performed.
      This study focused on analyzing injuries sustained in victims of falling in
      relation to different distances of fall. METHODS: Retrospective study of 352
      autopsy reports of falling victims brought to the forensic pathology department
      at Jordan University Hospital during the period from January 1990 to March 2016.
      RESULTS: Among 352 cases, 256 (72.7%) were males and 96 (27.3%) were females. 303
      (86.1%) cases showed accidental fall, 31 (8.8%) were suicidal, 2 (0.6%) were
      homicidal and un-clarified death in 16 (4.5%). Time of death was directly
      proportionate with the distance of fall. Victims fell from distances less than 3
      m were 123 (35%), most of them were children less than 7 years 50 (40.5%) and
      unemployed adults more than 45 years were 48 (39.1%). They showed multiple
      abrasions (62.6%), few contusions (64.2%) and absent laceration of the skin
      (84.5%). Victims fell from distances of 3-9 m were 123 (35%), most of them were
      male workers 56 (60.2%). They showed multiple abrasions (63.5%), few contusions
      (71%) and few lacerations of skin (50.5%). Victims fell from distances more than
      9 m were 136 (38.6%), most of them were male workers 71 (52.2%) and female
      servants 23 (17%). They showed few abrasions (80.9%), multiple contusions (64.7%)
      and few lacerations of skin (48.5%). The number of fractured limbs increases
      obviously with distances more than 3 m. Skull vault fractures were found in all
      distances, while skull base fractures showed in distances of 3-9 m and more than
      9 m. Head injury was the most common fatal injury in all distances. Chest
      injuries were prominent mainly in distances more than 3 m. While abdominal
      injuries were mainly prominent in distances more than 9 m. CONCLUSIONS: This
      study showed the effect of different distances of fall in causing different types
      of injuries in falling fatalities. Internal injuries were in a direct proportion
      with distances of fall, while external injuries showed a great importance in
      interpretation of the way of fall.

PMID- 29324322
TI  - Kinetic study of heavy metals Cu and Zn removal during sewage sludge ash
      calcination in air and N2 atmospheres.
AB  - Heavy metal control is essential during the thermochemical recovery of phosphorus
      (P) from sewage sludge ash (SSA). For medium volatile heavy metals, i.e. Cu and
      Zn, the effect of chlorine additive was complicated and more sensitive to
      temperature variation. So, in the in-depth study on the removal kinetics of Cu
      and Zn was necessary. Thus, the studies described in this paper considered the
      experiments and kinetic models of Cu and Zn removal in SSA through calcination
      under different atmospheres and temperatures. The results showed that within 15
      min, the removal of Cu and Zn was more effective at the same temperature in air
      than in N2. The result is consistent with kinetic analysis: Reaction activation
      energy of both Cu and Zn in an air atmosphere is lower than in N2. In addition,
      the reaction orders, energy and frequency factors of Cu and Zn removal reaction
      during SSA calcination at high temperature with air and N2 atmosphere were
      calculated.

PMID- 29324323
TI  - Multidisciplinary characterization of U(VI) sequestration by Acidovorax facilis
      for bioremediation purposes.
AB  - The contamination of the environment by U may affect plant life and consequently
      may have an impact on animal and human health. The present work describes U(VI)
      sequestration by Acidovorax facilis using a multidisciplinary approach combining
      wet chemistry, transmission electron microscopy, and spectroscopy methods (e.g.
      cryo-time resolved laser-induced fluorescence spectroscopy, extended X-ray
      absorption fine structure spectroscopy, and in-situ attenuated total reflection
      Fourier transform infrared spectroscopy). This bacterial strain is widely
      distributed in nature including U-contaminated sites. In kinetic batch
      experiments cells of A. facilis were contacted for 5 min to 48 h with 0.1 mM
      U(VI). The results show that the local coordination of U species associated with
      the cells depends upon time contact. U is bound mainly to phosphate groups of
      lipopolysaccharide (LPS) at the outer membrane within the first hour. And, that
      both, phosphoryl and carboxyl functionality groups of LPS and peptidoglycan of A.
      facilis cells may effectuate the removal of high U amounts from solution at 24-48
      h of incubation. It is clearly demonstrated that A. facilis may play an important
      role in predicting the transport behaviour of U in the environment and that the
      results will contribute to the improvement of bioremediation methods of U
      contaminated sites.

PMID- 29324324
TI  - Investigation of the factors that influence lead accumulation onto polyethylene:
      Implication for potable water plumbing pipes.
AB  - The influence of polymer aging, water pH, and aqueous Pb concentration on Pb
      deposition onto low density polyethylene (LDPE) was investigated. LDPE pellets
      were aged by ozonation at 85  degrees C. ATR-FTIR and X-ray photoelectron
      spectroscopy (XPS) analysis of aged LDPE surfaces showed that a variety of polar
      functional groups (>CO<, >CO, >COO) were formed during aging. These functional
      groups likely provided better nucleation sites for Pb(OH)2 deposition compared to
      new LDPE, which did not have these oxygen-containing functional groups. The type
      and amount of Pb species present on these surfaces were evaluated through XPS.
      The influence of exposure duration on Pb deposition onto LDPE was modeled using
      the pseudo-first-order equation. Distribution ratios of 251.5 for aged LDPE and
      69.3 for new LDPE showed that Pb precipitates had greater affinity for the
      surface of aged LDPE compared to new LDPE. Aged LDPE had less Pb surface loading
      at pH 11 compared to loading at pH 7.8. Pb surface loading for aged LDPE changed
      linearly with aging duration (from 0.5-7.5 h). Pb surface loading on both new and
      aged LDPE increased linearly with increasing Pb initial concentration. Greater Pb
      precipitation rates were found for aged LDPE compared to new LDPE at both tested
      pH values.

PMID- 29324325
TI  - Adsorption and separation of n/iso-pentane on zeolites: A GCMC study.
AB  - Separation of branched chain hydrocarbons and straight chain hydrocarbons is very
      important in the isomerization process. Grand canonical ensemble Monte Carlo
      simulations were used to investigate the adsorption and separation of iso-pentane
      and n-pentane in four types of zeolites: MWW, BOG, MFI, and LTA. The computation
      of the pure components indicates that the adsorption capacity is affected by
      physical properties of zeolite, like pore size and structures, and isosteric
      heat. In BOG, MFI and LTA, the amount of adsorption of n-pentane is higher than
      iso-pentane, while the phenomenon is contrary in MWW. For a given zeolite, a
      stronger adsorption heat corresponds to a higher loading. In the binary mixture
      simulations, the separation capacity of n-and iso-pentane increases with the
      elevated pressure and the increasing iso-pentane composition. The adsorption
      mechanism and competition process have been examined. Preferential adsorption
      contributions prevail at low pressure, however, the size effect becomes important
      with the increasing pressure, and the relatively smaller n-pentane gradually
      competes successfully in binary adsorption. Among these zeolites, MFI has the
      best separation performance due to its high shape selectivity. This work helps to
      better understand the adsorption and separation performance of n- and iso-pentane
      in different zeolites and explain the relationship between zeolite structures and
      adsorption performance.

PMID- 29324326
TI  - Studying the recognition mechanism of TcaR and ssDNA using molecular dynamic
      simulations.
AB  - The transcription regulator teicoplanin-associate locus regulator (TcaR) plays a
      vital role in interfering with ssDNA replication and resisting ssDNA phage
      invasion. Although recent studies demonstrated that TcaR had strong interaction
      with ssDNA, the dynamics and interaction mechanism of dimeric TcaR bound to ssDNA
      have not been rationalized at the atomic level. In our study, MD simulations
      combined with MM-GB/SA calculations were employed to study recognition mechanism
      between TcaR and ssDNA. The results illuminate that electrostatic interaction is
      the main driving force for the binding process. We put forward that six anchoring
      residues (Arg70, Arg71, Ser188, Gln191, Arg221 and Arg222) play a vital role in
      stabilizing the ssDNA by forming strong hydrogen bond and salt bridge
      interactions. TcaR undergoes the asymmetric conformational changes at the wHTH
      domain upon binding to ssDNA. This may be attributed to the changing of
      electrostatic potential, enhanced contacts and salt bridge interaction. The
      present study provides new insights into the recognition mechanism of TcaR bound
      to ssDNA, which could contribute to understanding about the multiple TcaR
      functions in staphylococci enrich our understanding of MarR family.

PMID- 29324327
TI  - Elucidating the interfaces involved in CARD-CARD interactions mediated by NLRP1
      and Caspase-1 using molecular dynamics simulation.
AB  - Inflammasomes are the multi-protein caspase-activating complexes mainly assembled
      by the sensor proteins (NLRs/ALRs), adaptor molecule (ASC) and effector molecule
      pro-caspase-1 for the production and release of proinflammatory cytokines, IL
      1beta and IL-18. NLRP1 is the first NLR known to assemble the multi-protein
      complex. Unlike NLRP3, NLRP1 has an additional effector binding domain (CARD) at
      the carboxyl-terminal, which is reported to interact with pro-caspase-1
      (precluding the recruitment of ASC) for the transmission of danger signals. So
      far no direct interaction has been observed between the NLRP1 and CASP1 at the
      structural level. In this study, an attempt has been made to elucidate the
      possible mode of interaction(s) between CASP1 and NLRP1 CARDs using structural
      bioinformatics approaches. The results revealed that the type-Ia patch of
      CASP1CARD (R10, K11, and R55) is probably the favorable interface for 1:1
      interaction. Moreover, the interactions mediated in the type-II and/(or) type-III
      interfaces of counter CARDs can also be not ruled out altogether. Overall, the
      findings of this study can be beneficial in understanding the underlying
      molecular mechanism(s) associated with NLRP1-mediated inflammasome.

PMID- 29324328
TI  - Long-term outcomes after percutaneous renal cryoablation performed with
      adjunctive techniques.
AB  - OBJECTIVE: To review the technical success of image-guided percutaneous
      cryoablation of renal masses in difficult anatomic locations using adjunctive
      techniques to displace critical structures away from the ablation zone, while
      also reporting longer-term outcomes within this patient population. METHODS: An
      IRB approved, retrospective analysis of 92 renal masses treated with percutaneous
      cryoablation revealed 15 cases utilizing adjunctive techniques. Tumor size and
      distance to adjacent organ before and after adjunctive technique and long-term
      outcomes were evaluated. RESULTS: The adjunctive techniques used were
      hydrodissection (n=15) and angioplasty balloon interposition (n=1). Before and
      after adjunctive technique, median tumor proximity to closest organ was 4mm and
      26mm, respectively. All cases had appropriate ablation zones and protection of
      adjacent critical structures. There is no evidence of recurrence or complication
      on follow-up (median 51months). CONCLUSIONS: Adjunctive techniques to ablate
      renal masses in difficult locations provide technical success, safety, and
      favorable long-term outcomes.

PMID- 29324329
TI  - Cystic mediastinal masses and the role of MRI.
AB  - While some cystic masses can be definitively diagnosed on CT, others remain
      indeterminate. Because of its intrinsic superior soft tissue resolution, MR is an
      important tool in the evaluation of select mediastinal masses that are
      incompletely characterized on CT. This review describes how non-vascular MR
      provides greater diagnostic precision in the evaluation of indeterminate cystic
      mediastinal masses on CT. It also emphasizes key MR pulse sequences for optimal
      evaluation of problematic mediastinal masses.

PMID- 29324330
TI  - Probing the mechanistic principles of bacterial cell division with super
      resolution microscopy.
AB  - Bacterial cell division takes place almost entirely below the diffraction limit
      of light microscopy, making super-resolution microscopy ideally suited to
      interrogating this process. I review how super-resolution microscopy has advanced
      our understanding of bacterial cell division. I discuss the mechanistic
      implications of these findings, propose physical models for cell division
      compatible with recent data, and discuss key outstanding questions and future
      research directions.

PMID- 29324331
TI  - Influence of pre-analytical time and temperature conditions on serum thromboxane
      B2 levels.

PMID- 29324332
TI  - Impaired plasminogen binding in patients with venous thromboembolism: Association
      with protein carbonylation.
AB  - INTRODUCTION: Venous thromboembolism (VTE) is associated with hypofibrinolysis.
      Its mechanisms are poorly understood. We investigated plasminogen-fibrin
      interaction and its association with fibrinolytic capacity and protein
      oxidation/carbonylation in VTE patients. MATERIALS AND METHODS: Plasma-purified
      plasminogen conversion to plasmin and surface plasmon resonance employed for
      plasminogen-fibrin interactions were individually evaluated in all healthy
      controls and non-anticoagulated patients following VTE, 10-23months since the
      event. We also assessed plasma fibrin clot permeability (Ks), clot lysis time
      (LT), activators and inhibitors of fibrinolysis together with
      oxidation/carbonylation markers. RESULTS: VTE patients had impaired plasminogen
      binding to fibrin (apparent Kd, +290%, p=0.002), reduced rate of plasmin
      generation (-4.7%, p=0.001), and longer LT (+18.6%, p<0.001) compared with
      controls. Fibrinogen and Ks were similar in both groups. Apparent Kd correlated
      with LT (r=0.43, p=0.037), tissue plasminogen activator-plasminogen activator
      inhibitor 1 (tPA-PAI-1) complexes (r=0.63, p=0.012), and active PAI-1 (r=0.49,
      p=0.03). Compared with controls, VTE patients had higher thiobarbituric acid
      reactive substances (TBARS), total protein carbonyl content (PC), and lower total
      antioxidant capacity (all p<0.001), that all were associated with LT (r=0.61,
      r=0.56, and r=-0.47, respectively, all p<0.05). Impaired plasminogen binding to
      fibrin reflected by apparent Kd positively correlated with TBARS (r=0.48,
      p=0.032) and PC (r=0.54, p=0.013) in the whole group. CONCLUSIONS: Plasminogen
      fibrin interactions are altered in young and middle-aged VTE patients, without
      known thrombophilias, except increased factor VIII. The mechanisms underlying
      these phenomena remain to be established.

PMID- 29324333
TI  - Management of direct oral anticoagulant associated bleeding: Results of a
      multinational survey.

PMID- 29324334
TI  - Rivaroxaban versus warfarin for the prevention of post-thrombotic syndrome.
AB  - INTRODUCTION: Despite treatment of acute deep vein thrombosis (DVT) with low
      molecular weight heparin and warfarin, up to 50% of patients develop post
      thrombotic syndrome (PTS). Our aims were to assess whether treatment of DVT with
      rivaroxaban would reduce the rate of subsequent PTS and improve health-related
      quality of life (HRQoL) as compared to conventional anticoagulation with low
      molecular weight heparin (LMWH)/warfarin. MATERIALS AND METHODS: Consecutive
      patients with an objectively confirmed DVT diagnosed between 2011 and 2014 and
      treated with either rivaroxaban or warfarin were included in this study 24 (+/-6)
      months after DVT. PTS was assessed using the Patient Reported Villalta scale.
      HRQoL was assessed using the EQ-5D-3L and VEINES-QOL/Sym questionnaires. RESULTS:
      Total 309 patients were included, 161 (52%) treated with rivaroxaban and 148
      (48%) with warfarin. Rivaroxaban-treated patients had a lower rate of PTS (45%:
      95% confidence interval [CI] 37 to 52) compared to those treated with warfarin
      (59%: 95% CI 51 to 66, absolute risk difference 14%: 95% CI 3 to 25, odds ratio
      (OR) 0.6, P = .01). The adjusted OR for development of PTS was 0.5 (95% CI: 0.3
      to 0.8, P = .01) in patients treated with rivaroxaban. HRQoL was significantly
      better in the rivaroxaban-treated patients. HRQoL measured by EQ-VAS (P = .002)
      and VEINES-QOL/Sym (P = .005/P = .003) remained significantly better after
      adjustment. CONCLUSIONS: Patients treated with rivaroxaban had lower rate of PTS
      and better HRQoL after DVT compared to patients treated with warfarin. However,
      these results should be interpreted with caution due to the limitation imposed by
      study design.

PMID- 29324335
TI  - Efficient synthesis and first regioselective C-6 direct arylation of imidazo[2,1
      c][1,2,4]triazine scaffold and their evaluation in H2O2-induced oxidative stress.
AB  - Oxidative stress and apoptosis are both associated with various acute and chronic
      disorders. Thus, the aim of the present study is to synthesize imidazo[2,1
      c][1,2,4]triazines derivatives and to evaluate their effects in H2O2-induced
      oxidative stress in human neuroblastoma cell line (SH-SY5Y cells). The effects of
      the compounds on cell viability were measured by MTT assay and the changes in
      stress and apoptosis-related proteins were investigated by PathScan(r) Stress and
      Apoptosis Signaling Antibody Array kit and Western Blot technique. In particular,
      four compounds were found to protect SH-SY5Y cells from H2O2-induced toxicity by
      increasing Bcl-2/Bax ratio, regulating PI3-K/Akt cascade and inhibiting the ERK
      pathway.

PMID- 29324336
TI  - New 1,5 and 2,5-disubstituted tetrazoles-dependent activity towards surface
      barrier of Candida albicans.
AB  - A series of novel tetrazole derivatives was synthetized using N-alkylation or
      Michael-type addition reactions, and screened for their fungistatic potential
      against Candida albicans (the lack of endpoint = 100%). Among them, the selected
      compounds 2d, 4b, and 6a differing in substituents at the tetrazole ring were non
      toxic to Galleria mellonella larvae in vivo and exerted slight toxicity against
      Caco-2 in vitro (CC50 at 256 MUg/mL). An antagonistic effect of tetrazole
      derivatives 2d, 4b, and 6a respectively in combination with Fluconazole was shown
      using the checker board and colorimetric methods (fractional inhibitory
      concentration indexes FICIs >1). The most active 2d and 6a displayed an inverse
      relation between MICs in the presence of exogenous ergosterol, the effect was
      opposite to Itraconazole and Amphotericin B. The differences between 6a's and
      2d's action mode were noted. Combining both flow cytometry and fluorescence image
      analyses respectively showed the complexity of planktonic and biofilm cell demise
      mode under the tetrazole derivatives tested. The following evidences for 6a's
      interaction with fungal membrane were noted: necrosis-like programmed cell death
      (97.03 +/- 0.88), DNA denaturation (no laddering), mitochondrial damage (XTT
      assay), reduced adhesion to human epithelium (>50% at 0.0313 MUg/mL, p <= .05),
      irregular deposit of chitin, and attenuated morphogenesis in mature biofilm. The
      treatment with 6a reduced pathogenicity of C. albicans during infection in G.
      mellonella. Contrariwise, 2d enhancing fungal adhesion displayed mechanism
      targeted to the cell wall (due to the presence of 3-chloropropyl clubbed with
      aryltetrazole) in the presence of osmotic protector. Under 2d, the accidental
      cell death (88.60% +/- 4.81) was observed. In conclusion, all tetrazole
      derivatives were obtained in satisfactory yields (60-95%) using efficient, simple
      and not expensive methods. Fungistatic and slightly anticancer tetrazole
      derivatives with the novel action mode can circumvent an appearance of antifungal
      resistant strains. These results indicate that they are worthy of further
      studies.

PMID- 29324337
TI  - Amino acid conjugated antimicrobial drugs: Synthesis, lipophilicity- activity
      relationship, antibacterial and urease inhibition activity.
AB  - Present work describes the in vitro antibacterial evaluation of some new amino
      acid conjugated antimicrobial drugs. Structural modification was attempted on the
      three existing antimicrobial pharmaceuticals namely trimethoprim, metronidazole,
      isoniazid. Twenty one compounds from seven series of conjugates of these drugs
      were synthesized by coupling with some selected Boc-protected amino acids. The
      effect of structural features and lipophilicity on the antibacterial activity was
      investigated. The synthesized compounds were evaluated against five standard
      American type culture collection (ATCC) i.e. Staphylococcus aureus, Bacillus
      subtilis, Escherichia coli, Pseudomonas aeruginosa and Salmonella typhi strains
      of bacteria. Our results identified a close relationship between the
      lipophilicity and the activity. Triazine skeleton proved beneficial for the
      increase in hydrophobicity and potency. Compounds with greater hydrophobicity
      have shown excellent activities against Gram-negative strains of bacteria than
      Gram-positive. 4-amino unsubstituted trimethoprim-triazine derivative 7b have
      shown superior activity with MIC = 3.4 MUM (2 MUg/mL) for S. aureus and 1.1 MUM
      (0.66 MUg/mL) for E. coli. The synthesized compounds were also evaluated for
      their urease inhibition study. Microbial urease from Bacillus pasteurii was
      chosen for this study. Triazine derivative 7a showed excellent inhibition with
      IC50 = 6.23 +/- 0.09 MUM. Docking studies on the crystal structure of B.
      pasteurii urease (PDB ID 4UBP) were carried out.

PMID- 29324338
TI  - Identification of novel 2-benzoxazolinone derivatives with specific inhibitory
      activity against the HIV-1 nucleocapsid protein.
AB  - In this report, we present a new benzoxazole derivative endowed with inhibitory
      activity against the HIV-1 nucleocapsid protein (NC). NC is a 55-residue basic
      protein with nucleic acid chaperone properties, which has emerged as a novel and
      potential pharmacological target against HIV-1. In the pursuit of novel NC
      inhibitor chemotypes, we performed virtual screening and in vitro biological
      evaluation of a large library of chemical entities. We found that compounds
      sharing a benzoxazolinone moiety displayed putative inhibitory properties, which
      we further investigated by considering a series of chemical analogues. This
      approach provided valuable information on the structure-activity relationships of
      these compounds and, in the process, demonstrated that their anti-NC activity
      could be finely tuned by the addition of specific substituents to the initial
      benzoxazolinone scaffold. This study represents the starting point for the
      possible development of a new class of antiretroviral agents targeting the HIV-1
      NC protein.

PMID- 29324339
TI  - Novel donepezil-like N-benzylpyridinium salt derivatives as AChE inhibitors and
      their corresponding dihydropyridine "bio-oxidizable" prodrugs: Synthesis,
      biological evaluation and structure-activity relationship.
AB  - As an extension of our previous work on donepezil-based "bio-oxidizable" prodrug
      approach, two new classes of N-benzylpyridinium donepezil analogues in tetralone
      B2 and acetophenone B3 series and a new set of indanone derivatives B1 were
      investigated along with the corresponding dihydropyridine prodrugs A1-3. A total
      of fifty one N-benzylpyridinium quaternary donepezil analogues B1-3 and twenty
      two prodrugs A1-3 were synthesized and evaluated for their inhibitory activities
      against hAChE and eqBuChE. While most prodrugs A1-3 were demonstrated to be
      inactive against AChE (IC50 > 10 MUM), a large number of the corresponding N
      benzylpyridinium salt B1-3 exhibited appealing three-to-one-digit nanomolar hAChE
      inhibitory activities and even reaching subnanomolar activity (IC50 = 0.36 nM).
      In addition, in silico docking studies were conducted for several compounds to
      explain the more relevant in vitro results. Lastly, the influence of the two
      stereogenic centers in prodrugs A was also evaluated, highlighting not only
      marked differences in residual AChE inhibitory activity of the four separated
      isomers of prodrug 23h (IC50 ranging from 173 nM to 10 MUM) but also significant
      variations of the oxidation rate between two separated diastereoisomers of
      prodrug 24a. This work provides useful information in the search of a preclinical
      candidate to conduct further development of this attractive "bio-oxidizable"
      prodrug strategy.

PMID- 29324340
TI  - Antimalarial naphthoquinones. Synthesis via click chemistry, in vitro activity,
      docking to PfDHODH and SAR of lapachol-based compounds.
AB  - Lapachol is an abundant prenyl naphthoquinone occurring in Brazilian Bignoniaceae
      that was clinically used, in former times, as an antimalarial drug, despite its
      moderate effect. Aiming to search for potentially better antimalarials, a series
      of 1,2,3-triazole derivatives was synthesized by chemical modification of
      lapachol. Alkylation of the hydroxyl group gave its propargyl ether which, via
      copper-catalyzed cycloaddition (CuAAC) click chemistry with different organic
      azides, afforded 17 naphthoquinonolyl triazole derivatives. All the synthetic
      compounds were evaluated for their in vitro activity against chloroquine
      resistant Plasmodium falciparum (W2) and for cytotoxicity to HepG2 cells.
      Compounds containing the naphthoquinolyl triazole moieties showed higher
      antimalarial activity than lapachol (IC50 123.5 MUM) and selectivity index (SI)
      values in the range of 4.5-197.7. Molecular docking simulations of lapachol,
      atovaquone and all the newly synthesized compounds were carried out for
      interactions with PfDHODH, a mitochondrial enzyme of the parasite respiratory
      chain that is essential for de novo pyrimidine biosynthesis. Docking of the
      naphthoquinonolyl triazole derivatives to PfDHODH yielded scores between -9.375
      and -14.55 units, compared to -9.137 for lapachol and -12.95 for atovaquone and
      disclosed the derivative 17 as a lead compound. Therefore, the study results show
      the enhancement of DHODH binding affinity correlated with improvement of SI
      values and in vitro activities of the lapachol derivatives.

PMID- 29324341
TI  - Biotin conjugated organic molecules and proteins for cancer therapy: A review.
AB  - The main transporter for biotin is sodium dependent multivitamin transporter
      (SMVT), which is overexpressed in various aggressive cancer cell lines such as
      ovarian (OV 2008, ID8), leukemia (L1210FR), mastocytoma (P815), colon (Colo-26),
      breast (4T1, JC, MMT06056), renal (RENCA, RD0995), and lung (M109) cancer cell
      lines. Furthermore, its overexpression was found higher to that of folate
      receptor. Therefore, biotin demand in the rapidly growing tumors is higher than
      normal tissues. Several biotin conjugated organic molecules has been reported
      here for selective delivery of the drug in cancer cell. Biotin conjugated
      molecules are showing higher fold of cytotoxicity in biotin positive cancer cell
      lines than the normal cell. Nanoparticles and polymer surface modified drugs and
      biotin mediated cancer theranostic strategy was highlighted in this review. The
      cytotoxicity and selectivity of the drug in cancer cells has enhanced after
      biotin conjugation.

PMID- 29324342
TI  - Peramivir conjugates as orally available agents against influenza H275Y mutant.
AB  - Peramivir is an efficacious neuraminidase (NA) inhibitor for treatment of
      influenza by intravenous administration. However, the efficacy of peramivir
      toward the H275Y mutant is appreciably reduced. To address this drawback,
      conjugation of peramivir with caffeic acid is devised in this study to enhance
      the binding affinity with neuraminidases. The C2-OH group of peramivir is
      elaborated to link with caffeate derivatives, giving the desired conjugates 8 and
      9 that possess potent NA inhibitory activity against both wild-type and H275Y
      viruses with the IC50 values in nanomolar range. The molecular modeling reveals
      that the caffeate moiety of conjugate 9 prefers to reside in the 295-cavity of
      H275Y neuraminidase, thus providing additional hydrogen bonds and hydrophobic
      interactions to compensate the reduced binding affinity of the peramivir moiety
      due to Glu-276 dislocation in H275Y mutant. In comparison with peramivir, the
      lipophilicity of conjugates 8 and 9 also increases by incorporation of the
      caffeate moiety. Thus, conjugates 8 and 9 offer better effect to protect MDCK
      cells from infection of H275Y virus with low EC50 value (~17 nM). Administration
      of conjugates 8 or 9 by oral gavage is effective in treatment of mice that are
      infected by lethal dose of wild-type or H275Y influenza viruses. Considering drug
      metabolism, since the ester linkage in conjugate 8 is susceptible to hydrolysis
      in plasma, conjugate 9 with robust amide linkage may be a better candidate for
      development into orally available anti-influenza drug that is also active to
      mutant viruses.

PMID- 29324343
TI  - Substituted tetrahydroisoquinolines: synthesis, characterization, antitumor
      activity and other biological properties.
AB  - This work deals with the molecular design, synthesis and biological activity of a
      series of tetrahydro[1,4]dioxanisoquinolines and dimethoxyisoquinoline analogues.
      This study describes the synthesis strategy of these potential antitumor
      compounds, their multi-step synthesis and their optimization. A series of
      tetrahydroisoquinolines was synthesized and their cytotoxicity evaluated. Some of
      these tetrahydroisoquinolines showed promising KRas inhibition, antiangiogenesis
      activity and antiosteoporosis properties. Molecular modeling studies showed that
      compound 12 bind in the p1 pocket of the KRas protein making interactions with
      the hydrophobic residues Leu56, Tyr64, Tyr71 and Thr74 and hydrogen bonds with
      residues Glu37 and Asp38.

PMID- 29324344
TI  - Anti-biofilm effect of novel thiazole acid analogs against Pseudomonas aeruginosa
      through IQS pathways.
AB  - IQS has been proven to be a new quorum sensing (QS) system against bacterial
      biofilm formation, which is activated in the common phosphate-limiting
      environment of infected tissues taking over the central las system. Up to now,
      numerous biofilm inhibitors which function by affecting traditional QS system
      have been reported. However, no compound has been reported to exert anti-biofilm
      activity through IQS system. Herein, various novel IQS derivatives were
      synthesized by the reaction of thiazole-4-carboxylic acid with different linear
      alcohols (R-OH) or amines (R-NH2). IQS derivatives with four carbon chain length
      of R group were found to present the best biofilm inhibition activity. Compound B
      11 as the model molecule was observed to inhibit biofilm formation only under
      phosphate-limiting condition, and increase in B-11 concentration significantly
      reduced the expression of rhlA-gfp and pqsA-gfp, but lasB-gfp. Moreover, B-11
      reduced production of virulence factors of rhamnolipid and pyocyanin under
      phosphate limitation. These observations indicated that the synthesized compounds
      possessed the anti-biofilm activity through IQS pathways rather than traditional
      QS pathways, which pave a path for future molecular design against bacterial
      biofilm formation.

PMID- 29324345
TI  - Synthesis and biological evaluation of a series of multi-target N-substituted
      cyclic imide derivatives with potential antipsychotic effect.
AB  - In the present study, a series of multi-target N-substituted cyclic imide
      derivatives which possessed potent dopamine D2, serotonin 5-HT1A and 5-HT2A
      receptors properties were synthesized and evaluated as potential antipsychotics.
      Among these compounds, (3aR,4R,7S,7aS)-2-(4-(4-(benzo[b]thiophen-4-yl)piperazin-1
      yl)butyl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione
      hydrochloride (3d) held a promising pharmacological profile. 3d not only showed
      potent and balanced in vitro activities on D2/5-HT1A/5-HT2A receptors, but also
      endowed with low to moderate activities on 5-HT2C, H1, alpha1A, M3 receptors and
      hERG channel, suggesting a low liability to induce side effects such as weight
      gain, orthostatic hypotension and QT prolongation. In animal behavioral studies,
      3d reduced phencyclidine-induced hyperlocomotion with a high threshold for
      catalepsy induction. Compound 3d was selected as a potential antipsychotic
      candidate for further development.

PMID- 29324346
TI  - Synthesis and biological characterization of novel rose bengal derivatives with
      improved amphiphilicity for sono-photodynamic therapy.
AB  - Sono-Photodynamic therapy (SPDT) utilizing ultrasound and light has been
      demonstrated that this novel approach can lower dosage resulting in reduction of
      the potential side effects caused by sensitizers. Recently, a new formulation of
      rose bengal (RB) as an intralesional injection has completed clinical trials
      phase II for PDT treatment of melanoma cancer. However, the inherent unfavorable
      pharmacological properties of RB hindered its extensive clinical development.
      With the aim to identify new RB derivatives (RBDs) with enhanced photodynamic and
      sonodynamic anticancer efficiency, a series of amphiphilic RBDs have been
      designed, synthesized and biological characterized. Among them, RBD4
      significantly improved cellular uptake and enhanced intracellular ROS generation
      efficiency upon light and ultrasound irradiation, resulting in dramatically
      improved anticancer potency. Notably, RBD4 has a relative potency similar to
      sinoporphyrin sodium (DVDMS), indicating its further potential application for
      SPDT.

PMID- 29324347
TI  - Design, synthesis and biological evaluation of 7H-pyrrolo[2,3-d]pyrimidin-4-amine
      derivatives as selective Btk inhibitors with improved pharmacokinetic properties
      for the treatment of rheumatoid arthritis.
AB  - Bruton's tyrosine kinase (Btk) is a Tec family kinase with a well-defined role in
      the B cell receptor (BCR) and Fcgamma receptor (FcR) signaling pathways, which
      makes it a uniquely attractive target for the treatment of autoimmune diseases,
      such as rheumatoid arthritis (RA). We reported a series of compounds bearing 7H
      pyrrolo [2,3-d]pyrimidin-4-amine scaffold that potently inhibited Btk in vitro.
      Analysis of the structure-activity relationships (SAR) and drug-like profiles led
      to the discovery of the optimal compound B16. B16 preferentially inhibited Btk
      (IC50 = 21.70 +/- 0.82 nM) over closely related kinases with moderate
      selectivity. Cell-based tests also confirmed that B16 significantly inhibited Btk
      Y223 auto-phosphorylation and PLCgamma2 Y1217 phosphorylation. MTT revealed that
      B16 displayed weak suppression against normal LO2, HEK293 and THP-1 cell lines
      with IC50 values over 30 MUM. Moreover, B16 showed very weak potential to block
      the hERG channel (IC50 = 11.10 MUM) in comparison to ibrutinib (IC50 = 0.97 MUM).
      Owing to its favorable physicochemical properties (ClogP = 2.53, aqueous
      solubility ~ 0.1 mg/mL), pharmacokinetic profiles (F = 49.15%, t1/2 = 7.02 h) and
      reasonable CYP450 profile, B16 exhibited potent anti-arthritis activity and
      similar efficacy to ibrutinib in reducing paw thickness in CIA mice. In
      conclusion, B16 is a potent, selective and durable inhibitor of Btk and has the
      potential to a safe and efficacious treatment for arthritis.

PMID- 29324348
TI  - Dependence among randomly acquired characteristics on shoeprints and their
      features.
AB  - Randomly acquired characteristics (RACs), also known as accidental marks, are
      random markings on a shoe sole, such as scratches or holes, that are used by
      forensic experts to compare a suspect's shoe with a print found at the crime
      scene. This article investigates the relationships among three features of a RAC:
      its location, shape type and orientation. If these features, as well as the RACs,
      are independent of each other, a simple probabilistic calculation could be used
      to evaluate the rarity of a RAC and hence the evidential value of the shoe and
      print comparison, whereas a correlation among the features would complicate the
      analysis. Using a data set of about 380 shoes, it is found that RACs and their
      features are not independent, and moreover, are not independent of the shoe sole
      pattern. It is argued that some of the dependencies found are caused by the
      elements of the sole. The results have important implications for the way
      forensic experts should evaluate the degree of rarity of a combination of RACs.

PMID- 29324349
TI  - Organic staining on bone from exposure to wood and other plant materials.
AB  - Determining the depositional environment and the postmortem alterations to a set
      of remains are necessary aspects of a forensic investigation to explain the
      circumstances surrounding the death of an individual. The present study examines
      organic staining as a method for reconstructing the depositional environment of
      skeletal remains and the taphonomic agents with which they came into contact.
      Organic staining results largely from tannins leaching from plant materials and
      therefore can be seen on bone deposited in wooden coffin environments or on
      terrestrial surfaces. The present study examines the hypothesis that the degree
      of staining observed on skeletal elements would increase as the length of
      exposure to the organic matter increased and that different plant materials and
      environments would leave different patterns or colorations of staining. The
      sample consisted of 165 pig (Sus scrofa) femora divided into four groups exposed
      to differing experimental conditions, including burial in direct contact with
      soil or burial in a simulated coffin environment, immersion in water with wood
      samples, and surface deposition with plant matter contact. The bones were removed
      once a month from their experimental environments and the level of staining was
      recorded qualitatively using the Munsell Soil Color Chart. In all of the
      experimental environments, staining was present after two months of exposure, and
      the color darkened across the bone surface with each episode of data collection.
      The results from the present study indicate that staining can manifest on bone
      within a relatively short time frame once skeletonization occurs and a variety of
      colorations or patterns of staining can manifest based on the plant material. The
      present research also demonstrates the potential of organic staining to aid in
      estimations of the postmortem interval as well as a depositional environmental
      reconstruction through plant species identification.

PMID- 29324350
TI  - Formation of phosphatidylethanol from endogenous phosphatidylcholines in animal
      tissues from pig, calf, and goat.
AB  - In the presence of alcohol, phosphatidylcholine (PC) is transformed to the direct
      alcohol biomarker phosphatidylethanol (PEth). This reaction is catalyzed by the
      enzyme phospholipase D (PLD) and dependent on substrate availability. As recent
      methods have solely focused on the determination of PEth, information about the
      PC composition was generally missing. To address this issue and monitor PC
      (16:0/18:1 and 16:0/18:2) and PEth (16:0/18:1 and 16:0/18:2) simultaneously, a
      reversed phase LC-MS/MS method based on a C8 core-shell column, coupled to a
      Sciex 5500 QTrap instrument was developed. By application of polarity switching,
      at first, PC was measured in ESI positive SRM mode, while PEth was determined at
      a later stage in ESI negative SRM mode. The PEth method was validated for human
      blood samples to show its robustness and subsequently applied for the
      investigation of systematic in vitro PEth formation in animal tissue samples
      (brain, kidney, liver, and blood) from a pig, a calf, and a goat. Homogenized
      tissue was incubated at 37 degrees C with varying ethanol concentrations from 1
      to 7g/kg (determined by HS-GC-FID) for 5h, whereby a sample was taken every
      30min. For all tissue samples, an increase in PEth was measurable. PEth
      concentrations formed in blood remained below the LLOQ, in agreement with
      literature. Data analysis of Michaelis-Menten kinetics and PC within the tissue
      provided a detailed insight about PEth formation, as the occurrence of PEth
      species can be linked to the observed PC composition. The results of this study
      show that PEth formation rates vary from tissue to tissue and among different
      species. Furthermore, new recommendations for PEth analysis are presented.

PMID- 29324351
TI  - Corrigendum to "Differences in combinations and concentrations of drugs of abuse
      in fatal intoxication and driving under the influence cases" [Forensic Sci. Int.
      281 (2017) 127-133].

PMID- 29324352
TI  - Administration of exercise-conditioned plasma alters muscle catalase kinetics in
      rat: An argument for in vivo-like Km instead of in vitro-like Vmax.
AB  - Maximal velocity (Vmax) is a well established biomarker for the assessment of
      tissue redox status. There is scarce evidence, though, that it does not probably
      reflect sufficiently in vivo tissue redox profile. Instead, the Michaelis
      constant (Km) could more adequately image tissue oxidative stress and, thus, be a
      more physiologically relevant redox biomarker. Therefore, the aim of the present
      study was to side-by-side compare Vmax and Km of an antioxidant enzyme after
      implementing an in vivo set up that induces alterations in tissue redox status.
      Forty rats were divided into two groups including rats injected with blood plasma
      originating from rats that had previously swam until exhaustion and rats injected
      with blood plasma originating from sedentary rats. Tail-vein injections were
      performed daily for 21 days. Catalase Vmax and Km measured in gastrocnemius
      muscle were increased after administration of the exercise-conditioned plasma,
      denoting enhancement of the enzyme activity but impairment of its affinity for
      the substrate, respectively. These alterations are potential adaptations
      stimulated by the administered plasma pointing out that blood is an active fluid
      capable of regulating tissue homeostasis. Our findings suggest that Km adequately
      reflects in vivo modifications of skeletal muscle catalase and seems to surpass
      Vmax regarding its physiological relevance and biological interpretation. In
      conclusion, Km can be regarded as an in vivo-like biomarker that satisfactorily
      images the intracellular environment, as compared to Vmax that could be aptly
      parallelized with a biomarker that describes tissue oxidative stress in an in
      vitro manner.

PMID- 29324353
TI  - Dietary habits during the 2 months following the Chernobyl accident and
      differentiated thyroid cancer risk in a population-based case-control study.
AB  - BACKGROUND: The Chernobyl nuclear power plant accident occurred in Ukraine on
      April 26th 1986. In France, the radioactive fallout and thyroid radiation doses
      were much lower than in highly contaminated areas. However, a number of risk
      projections have suggested that a small excess in differentiated thyroid cancer
      (DTC) might occur in eastern France due to this low-level fallout. In order to
      investigate this potential impact, a case-control study on DTC risk factors was
      started in 2005, focusing on cases who were less than 15 years old at the time of
      the Chernobyl accident. Here, we aim to evaluate the relationship between some
      specific reports of potentially contaminated food between April and June 1986 -
      in particular fresh dairy products and leafy vegetables - and DTC risk. METHODS:
      After excluding subjects who were not born before the Chernobyl accident, the
      study included 747 cases of DTC matched with 815 controls. Odds ratios were
      calculated using conditional logistic regression models and were reported for all
      participants, for women only, for papillary cancer only, and excluding
      microcarcinomas. RESULTS: The DTC risk was slightly higher for participants who
      had consumed locally produced leafy vegetables. However, this association was not
      stronger in the more contaminated areas than in the others. Conversely, the
      reported consumption of fresh dairy products was not statistically associated
      with DTC risk. CONCLUSION: Because the increase in DTC risk associated with a
      higher consumption of locally produced vegetables was not more important in the
      most contaminated areas, our study lacked power to provide evidence for a strong
      association between consumption of potentially contaminated food and DTC risk.

PMID- 29324354
TI  - An in-depth prognostic analysis of baseline blood lipids in predicting
      postoperative colorectal cancer mortality: The FIESTA study.
AB  - BACKGROUND: Dyslipidaemia is key to colorectal carcinogenesis, and the prediction
      of baseline triglycerides (TG), total cholesterol (TC), high- and low-density
      lipoprotein cholesterol (HDLC and LDLC) for postsurgical colorectal cancer
      mortality has not been researched. OBJECTIVES: We attempted to re-analyse the
      FIESTA database to assess the prognostic value of three informative lipid
      derivatives - AI (atherogenic index: (TC - HDLC)/HDLC), THR (TG/HDLC) and LHR
      (LDLC/HDLC) in predicting colorectal cancer mortality. METHODS: Based on the
      FIESTA database, 1318 patients received radical resection from 2000 to 2008, with
      the latest follow-up completed in December 2015. Median follow-up time was 58.6
      months. RESULTS: Total 1318 patients were randomly evenly divided into the
      derivation and validation groups. Overall, baseline AI and LHR were associated
      with the significantly increased risk of colorectal cancer mortality in both
      derivation (hazard ratio (HR): 1.41 and 1.35, respectively) and validation (HR:
      1.37 and 1.32, respectively) groups (all P < 0.001). The predictive performance
      of AI and LHR was remarkably enhanced in patients with female gender,
      former/current smoking, colon cancer, early stage, positive vein tumor embolus,
      normal weight, preoperative hypertension or diabetes comorbidities.
      Calibration/discrimination analyses revealed that adding AI or LHR to the
      traditional model had a better fit in both groups. A prognostic nomogram was
      finally constructed with good predictive accuracy and discriminative capability
      (C-index = 0.814, P < 0.001). CONCLUSION: We consolidated the prognostic
      superiority of AI and LHR in predicting colorectal cancer mortality over TNM
      stage.

PMID- 29324355
TI  - Drug-mediation formation of nanohybrids for sequential therapeutic delivery in
      cancer cells.
AB  - In order to overcome the multidrug resistance (MDR) of tumor cells, it is very
      important to develop nanocarriers which can effectively load drugs while
      releasing them in a sequential way. Herein, nanohybrids with such properties have
      been fabricated by a first loading of one anticancer drug onto a silicate
      nanodisk (Laponite (LP), 25 nm in diameter and 0.92 nm in thickness) and a
      subsequent assembly with a pH sensitive poly(N-vinylpyrrolidone) (PVP) as a
      protective layer, followed by a loading of with another anticancer drug. The
      resulting nanohybrids (LDPM) present a high drug encapsulation efficiency and
      long-term colloidal stability. However, if the two drugs are loaded onto LP
      before PVP decoration, the formed particles tend to form microsized aggregates
      with poor colloidal stability. In vitro release study indicates that LDPM can
      deliver the anticancer drugs in a sequential way, which can be further
      accelerated under acidic microenvironments mimicking both solid tumor and endo
      lysosomal compartments, exerting synergistic anticancer cytotoxicity. The drug
      mediated formation of nanocarriers may enlighten a design of novel nanoplatform
      for co-delivery of therapeutic agents, beyond anticancer drugs, in a combinative
      way for drug delivery applications.

PMID- 29324356
TI  - Inflammation induced ER stress affects absorptive intestinal epithelial cells
      function and integrity.
AB  - Recent studies have linked impairment of intestinal epithelial function in
      inflammatory bowel disease to the disturbance of endoplasmic reticulum
      homeostasis (ER) in response to stress. Most studies are on goblet and Paneth
      cells, which are considered more susceptible to stress due to their role in the
      protection of intestinal epithelium against microbes and harmful substances.
      However, studies on the role of inflammation-induced ER stress in absorptive
      intestinal cells are scarce. In this study, we show, using Caco-2 cells as a
      model of intestinal epithelial barrier, that inducing ER stress using a cocktail
      mixture of pro-inflammatory mediators [TNFalpha (50ng/ml), MCP1 (50ng/ml), and IL
      1beta (25ng/ml)] as observed in IBD patients induces ER stress and leads to
      significant changes in key proteins of the apical (sucrase-isomaltase (SI),
      dipeptidyl-peptidase (DPPIV), and ezrin) and basolateral (E-cadherin, zonula
      occludens (ZO-1), and connexin-43) membranes. Aberrant trafficking of SI, DPPIV
      was observed as early as 8h post-inflammation-induced ER stress and even in the
      absence of loss of intestinal cell integrity. The observed effect was associated
      with a re-localization of ezrin, ZO-1, and connexin-43, key differentiation and
      junction proteins. Collectively, this study shows that disruption of the
      trafficking of key digestive enzymes of the intestinal epithelium occur in
      response to inflammation induced ER stress before the loss of monolayer
      integrity.

PMID- 29324357
TI  - A pilot study of the role of the claustrum in attention and seizures in rats.
AB  - OBJECTIVE: The claustrum has been implicated in consciousness, and MRIs of
      patients with status epilepticus have shown increased claustral signal intensity.
      In an attempt to investigate the role of claustrum in cognition and seizures, we
      (1) assessed the effect of high-frequency stimulation (HFS) of the claustrum on
      performance in the operant chamber; (2) studied interclaustral and
      claustrohippocampal connectivity through cerebro-cerebral evoked potentials
      (CCEPs); and (3) investigated the role of claustrum in kainate-induced (KA)
      seizures. METHODS: Adult male Sprague-Dawley rats were trained in operant
      conditioning and implanted with electrodes in bilateral claustra and hippocampi.
      Claustrum HFS (50 Hz) was delivered bilaterally and unilaterally with increasing
      intensities from 50 to 1000 MUA, and performance scores were assessed. CCEPs were
      studied by averaging the responses to bipolar stimulations, 1-ms wide pulses at
      0.1 Hz to the claustrum. KA seizures were analyzed on video-EEG recordings.
      RESULTS: Generalized Estimating Equations analysis revealed that claustral
      stimulation reduced task performance scores relative to rest sessions (bilateral:
      -15.8 percentage points, p < 0.0001; unilateral: -15.2, p < 0.0001). With some
      stimulations, the rats showed a stimulus-locked decrease in attentiveness and,
      occasionally, an inability to complete the operant task. CCEPs demonstrated
      interclaustral and claustrohippocampal connectivity. Some KA seizures appeared to
      originate from the claustrum. CONCLUSIONS: Findings from the operant conditioning
      task suggest stimulation of the claustrum can alter attention or awareness. CCEPs
      demonstrated connectivity between the two claustra and between the claustrum and
      the hippocampi. Such connectivity may be part of the circuitry that underlies the
      alteration of awareness in limbic seizures. Lastly, KA seizures showed early
      involvement of the claustrum, a finding that also supports a possible role of the
      claustrum in the alteration of consciousness that accompanies dyscognitive
      seizures.

PMID- 29324358
TI  - Regulatory CD4 T cells inhibit HIV-1 expression of other CD4 T cell subsets via
      interactions with cell surface regulatory proteins.
AB  - During chronic HIV-1 infection, regulatory CD4 T cells (Tregs) frequently
      represent the largest subpopulation of CD4 T cell subsets, implying relative
      resistant to HIV-1. When HIV-1 infection of CD4 T cells was explored in vitro and
      ex vivo from patient samples, Tregs possessed lower levels of HIV-1 DNA and RNA
      in comparison with conventional effector and memory CD4 T cells. Moreover, Tregs
      suppressed HIV-1 expression in other CD4 T cells in an in vitro co-culture
      system. This suppression was mediated in part via multiple inhibitory surface
      proteins expressed on Tregs. Antibody blockade of CTLA-4, PD-1, and GARP on Tregs
      resulted in increased HIV-1 DNA integration and mRNA expression in neighboring
      CD4 T cells. Moreover, antibody blockade of Tregs inhibitory proteins resulted in
      increased HIV-1 LTR transcription in co-cultured CD4 T cells. Thus, Tregs inhibit
      HIV-1 infection of other CD4 T cell subsets via interactions with inhibitory cell
      surface proteins.

PMID- 29324359
TI  - Progress toward an enhanced vaccine: Eight marked attenuated viruses to porcine
      reproductive and respiratory disease virus.
AB  - Recombinant viruses of strain Ingelvac(r) PRRS porcine reproductive and
      respiratory syndrome virus (PRRSV) modified live virus vaccine were produced with
      two individual small in-frame deletions in nonstructural protein 2 (nsp2; Delta23
      and Delta87) and also the same deletions supplanted with foreign tags (Delta23
      V5, Delta23-FLAG, Delta23-S, Delta87-V5, Delta87-FLAG, Delta87-S). The viruses,
      but one (Delta87-FLAG), were stable for 10 passages and showed minimal effects on
      in vitro growth. Northern hybridization showed that the Delta23-tagged probe
      detected intracellular viral genome RNA as well as shorter RNAs that may
      represent heteroclite species, while the Delta87-tagged probe detected
      predominantly only genome length RNAs. When the tagged viruses were used to probe
      nsp2 protein in infected cells, perinuclear localization similar to native nsp2
      was seen. Dual infection of Delta23-S and Delta87-S viruses allowed some
      discrimination of individual tagged nsp2 protein, facilitating future research.
      The mutants could potentially also be used to differentiate infected from
      vaccinated animals.

PMID- 29324360
TI  - Evaluation of the zoonotic potential of multiple subgroups of clade 2.3.4.4
      influenza A (H5N8) virus.
AB  - Clade 2.3.4.4 H5N8 highly pathogenic avian influenza viruses (HPAIVs) have spread
      worldwide. Phylogenetic analysis identified two genetic groups of the H5N8 HPAIVs
      in South Korea; group A evolved further into four subgroups. Here, we examined
      the zoonotic potential, both in vivo and in vitro, of genetically distinct
      subgroups of H5N8 HPAIVs isolated in South Korea. When compared with other
      subgroups, A/mallard/Korea/H2102/2015 (H2102) virus caused relatively severe
      disease in mice at high doses. In ferrets, all H5N8 viruses replicated
      restrictively in the respiratory tract and did not induce significant clinical
      signs of influenza infection. In vitro studies, all viruses displayed a
      hemagglutinin phenotype that was poorly adapted for infection of mammals,
      although the H2102 virus exhibited higher replication kinetics at 33 degrees C
      than the others. Although H5N8 HPAIVs have not yet acquired all the
      characteristics required for adaptation to mammals, their ability to evolve
      continuously underscores the need for timely risk assessment.

PMID- 29324361
TI  - Simultaneous removal of atrazine and organic matter from wastewater using
      anaerobic moving bed biofilm reactor: A performance analysis.
AB  - In this study, an anaerobic moving bed biofilm reactor (AMBBR) was designed to
      biodegrade atrazine under mesophilic (32  degrees C) condition and then it was
      evaluated for approximately 1 year. After biofilm formation, acclimation, and
      enrichment of microbial population within the bioreactor, the effect of various
      operation conditions such as changes in the concentration of influent atrazine
      and sucrose, hydraulic retention time (HRT), and salinity on the removal of
      atrazine and chemical oxygen demand (COD) were studied. In optimum conditions,
      the maximum removal efficiency of atrazine and COD was 60.5% and 97.4%,
      respectively. Various models were developed to predict the performance of
      atrazine removal as a function of HRT during continuous digestion. Also,
      coefficients kinetics was studied and the maximum atrazine removal rate was
      determined by Stover - Kincannon model (rmax = 0.223 kgATZ/m3d). Increasing
      salinity up to 20 g/L NaCl in influent flow could inhibit atrazine biodegradation
      process strongly in the AMBBR reactor; whereas, the reactor could tolerate the
      concentrations less than 20 g/L easily. Results showed that AMBBR is feasible,
      easy, affordable, so suitable process for efficiently biodegrading toxic
      chlorinated organic compounds such as atrazine. There was no accumulation of
      atrazine in the biofilm and the loss of atrazine in the control reactor was
      negligible; this shows that atrazine removal mechanism in this system was due to
      co-metabolism.

PMID- 29324362
TI  - X-ray system simulation software tools for radiology and radiography education.
AB  - OBJECTIVES: To develop x-ray simulation software tools to support delivery of
      radiological science education for a range of learning environments and audiences
      including individual study, lectures, and tutorials. METHODS: Two software tools
      were developed; one simulated x-ray production for a simple two dimensional
      radiographic system geometry comprising an x-ray source, beam filter, test object
      and detector. The other simulated the acquisition and display of two dimensional
      radiographic images of complex three dimensional objects using a ray casting
      algorithm through three dimensional mesh objects. Both tools were intended to be
      simple to use, produce results accurate enough to be useful for educational
      purposes, and have an acceptable simulation time on modest computer hardware. The
      radiographic factors and acquisition geometry could be altered in both tools via
      their graphical user interfaces. A comparison of radiographic contrast
      measurements of the simulators to a real system was performed. RESULTS: The
      contrast output of the simulators had excellent agreement with measured results.
      The software simulators were deployed to 120 computers on campus. CONCLUSIONS:
      The software tools developed are easy-to-use, clearly demonstrate important x-ray
      physics and imaging principles, are accessible within a standard University
      setting and could be used to enhance the teaching of x-ray physics to
      undergraduate students. ADVANCES IN KNOWLEDGE: Current approaches to teaching x
      ray physics in radiological science lack immediacy when linking theory with
      practice. This method of delivery allows students to engage with the subject in
      an experiential learning environment.

PMID- 29324363
TI  - Documentation integrity: Authorship functionalities of EHR in a Saudi Arabian
      hospital.
AB  - This paper aims to evaluate the authorship, privacy capabilities and functions of
      QuadraMed and BestCare systems, implemented at the Ministry of National Guard
      Health Affairs (MNGHA) in Riyadh, Saudi Arabia. A survey was conducted by
      interviewing back-end users of the EMR system in the KAMC hospital to check the
      aforementioned systems' authorship capabilities. Both the systems scored the
      same, with the overall result being 146/165 including the compliance level, which
      represents 88% availability of all authorship functions. The Quadra system's non
      complying item was identified for only one entity, which is related to the lack
      of diagnosis documentation. It does not aid physicians in enhancing their ability
      to document diagnosis, which depends on coding and has not been implemented
      within the system so far. However, BestCare system provides documenting diagnosis
      depending on the coding part rather than free text, suggesting it is a promising
      system with enhanced functionalities.

PMID- 29324364
TI  - Automatic non-invasive heartbeat quantification of Drosophila pupae.
AB  - The importance of studying model organisms such as Drosophila melanogaster has
      significantly increased in recent biological research. Amongst others, Drosophila
      can be used to study heart development and heartbeat related diseases. Here we
      propose a method for automatic in vivo heartbeat detection of Drosophila
      melanogaster pupae based on morphological structures which are recorded without
      any dissection using FIM imaging. Our approach is easy-to-use, has low
      computational costs, and enables high-throughput experiments. After automatically
      segmenting the heart region of the pupa in an image sequence, the heartbeat is
      indirectly determined based on intensity variation analysis. We have evaluated
      our method using 47,631 manually annotated frames from 29 image sequences
      recorded with different temporal and spatial resolutions which are made publicly
      available. We show that our algorithm is both precise since it detects more than
      95% of the heartbeats correctly as well as robust since the same standardized set
      of parameters can be used for all sequences. The combination of FIM imaging and
      our algorithm enables a reliable heartbeat detection of multiple Drosophila pupae
      while simultaneously avoiding any time consuming preparation of the animals.

PMID- 29324365
TI  - How does social support relieve depression among flood victims? The contribution
      of feelings of safety, self-disclosure, and negative cognition.
AB  - BACKGROUND: Depression is one of the most common post-trauma symptoms that can be
      alleivated by social support. The purpose of this study was to examine the
      multiple mediating effects of social support on depression via feelings of
      safety, disclosure, and negative cognition. METHOD: One hundred and eighty-seven
      flood victims in Wuhu City, an area affected most severely by a flood during July
      2016, were selected to complete a self-report questionnaire package. RESULTS:
      Social support has four indirect negative effects on depression, including a one
      step indirect path to self-disclosure, 2 two-step paths from feelings of safety
      to self-disclosure, and from self-disclosure to negative cognition about self,
      and a three-step indirect path from feelings of life safety via self-disclosure
      to negative self-cognition. LIMITATIONS: All variables were measured using self
      report scales. CONCLUSION: Social support may relieve depression in flood victims
      by inducing feelings of safety and self-disclosure, and by relieving negative
      cognition.

PMID- 29324366
TI  - Size matters - The olfactory bulb as a marker for depression.
AB  - BACKGROUND: Major Depression is mainly related to structural and functional
      alterations in brain networks involving limbic and prefrontal regions. Reduced
      olfactory sensitivity in depression is associated with reduced olfactory bulb
      (OB) volume. We determined if the OB volume reduction is a specific biomarker for
      depression and whether its diagnostic accuracy allows its use as a valid
      biomarker to support its diagnosis. METHODS: 84 in-patients with mixed mental
      disorders and 51 age-matched healthy controls underwent structural MR imaging
      with a spin-echo T2-wheighted sequence. Individual OB volume was calculated
      manually (interrater-reliability = .81, p < .001) and compared between groups.
      Multiple regression analysis with OB volume as dependent variable and Receiver
      Operator Characteristic analysis to obtain its diagnostic accuracy for depression
      were ruled out. RESULTS: Patients exhibited a 13.5% reduced OB volume. Multiple
      regression analysis showed that the OB volume variation was best explained by
      depression (beta = -.19), sex (beta = -.31) and age (beta = -.29), but not by any
      other mental disorder. OB volume attained a diagnostic accuracy of 68.1% for
      depression. LIMITATIONS: The patient group mainly contained highly comorbid
      patients with mostly internalizing disorders which limits the generalisability of
      the results of the regression analysis. CONCLUSION: The OB may serve as a marker
      for depression. We assume that reduced neural olfactory input to subsequent
      limbic and salience processing structures moderates this relation. However, the
      OB was in an inferior position compared to conventional questionnaires for
      diagnosis of depression. Combination with further structural or functional
      measurements is suggested.

PMID- 29324367
TI  - Integrating situation-specific dysfunctional expectations and dispositional
      optimism into the cognitive model of depression - A path-analytic approach.
AB  - BACKGROUND: Dysfunctional expectations are considered to be core features of
      mental disorders and, in particular, major depression. The aim of the present
      study was to integrate two important types of expectations into the cognitive
      model of depression: situation-specific dysfunctional expectations (SDE) and
      dispositional optimism (DO). It was hypothesized that the influence of both DO
      and intermediate beliefs (IB) on depressive symptoms would be mediated via SDE.
      METHODS: We examined 95 individuals (age M = 40.7, 68.1% female) with a diagnosed
      major depressive disorder from two inpatient clinics and one outpatient clinic.
      Measurements used in the study included the Depressive Expectations Scale,
      Dysfunctional Attitudes Scale, Life Orientation Test Revised, and Beck's
      Depression Inventory-II. Relationships between the constructs were analyzed using
      path-analytic models with bias-corrected bootstrapping confidence intervals.
      RESULTS: Results indicate that the effect of IB on depressive symptoms was fully
      mediated via SDE, while the effect of DO on depressive symptoms was partly
      mediated via SDE. IB and DO moderately correlated with each other. LIMITATIONS:
      Due to the cross-sectional design of the study, it is not possible to draw
      unambiguous conclusions regarding the causality of the suggested relationships.
      CONCLUSIONS: The present study stresses the crucial role of dysfunctional
      expectations for major depression. Moreover, it reveals that SDEs as expectations
      with a high level of situational specificity may pose an important link between
      global cognitions and depressive symptoms. Given this situational specificity,
      SDEs are amenable to disconfirmation through behavioral experiments and may
      therefore be a promising target for cognitive-behavioral interventions.

PMID- 29324368
TI  - Childhood disadvantage, education, and psychological distress in adulthood: A
      three-wave population-based study.
AB  - BACKGROUND: We assessed the mediating role of education in the association
      between childhood disadvantage and psychological distress in adulthood using
      longitudinal data collected in three waves, from 1994 to 2008, in the framework
      of the Tromso Study (N = 4530), a cohort that is representative of men and women
      from Tromso. METHODS: Education was measured at a mean age of 54.7 years, and
      psychological distress in adulthood was measured at a mean age of 61.7 years.
      Ordinary least square regression analysis was used to assess the associations
      between childhood disadvantage, education, and psychological distress in
      adulthood. The indirect effects and the proportion (%) of indirect effects of
      childhood disadvantage (via education) on psychological distress in adulthood
      were assessed by mediation analysis. RESULTS: Childhood disadvantage was
      associated with lower education and higher psychological distress in adulthood (p
      < 0.05). Lower education was associated with a higher psychological distress in
      adulthood (p < 0.05). A minor proportion (7.51%, p < 0.05) of the association
      between childhood disadvantage and psychological distress in adulthood was
      mediated by education. LIMITATIONS: Childhood disadvantages were measured
      retrospectively. CONCLUSION: The association between childhood disadvantage and
      psychological distress in adulthood is primarily independent of education.

PMID- 29324370
TI  - Model-based comparing efficacy of fluoxetine between elderly and non-elderly
      participants with major depressive disorder.
AB  - BACKGROUND: The high heterogeneity was existed among the studies of the elderly
      participants with major depressive disorder (MDD), which may lead to incorrect
      conclusions in the previous meta-analysis. This study used model based meta
      analysis to compare the efficacy of fluoxetine between the elderly and non
      elderly participants with MDD and to explain the heterogeneity among the studies.
      METHODS: A comprehensive literature search was conducted in the public databases,
      involving utilization of fluoxetine for treating MDD in the acute-phase. The time
      efficacy model was established based on the changes of the Hamilton Depression
      Rating Scale (HDRS) score compared to baseline level. The efficacy features and
      related factors of fluoxetine in the elderly participants were investigated by
      comparing with the non-elderly population. RESULTS: Sixty-one studies
      encompassing 4058 participants were included in the analysis. We found the trial
      design of placebo controlled vs. comparator controlled was a significant impact
      factor for the efficacy of fluoxetine. The typical decrease rate of HDRS score in
      the elderly participants was strikingly lower than that of the non-elderly
      participants at week 8, with 39.9% vs. 49.1% in the placebo controlled trial and
      46.5% vs. 57.2% in the comparator controlled trial. LIMITATION: The efficacy of
      other antidepressants except fluoxetine in the elderly participants need to be
      explored in the future study. CONCLUSIONS: The efficacy of fluoxetine in the
      elderly participants was lower than that of the non-elderly participants. The
      heterogeneity of the trial design should be distinguished when comparing the
      efficacy of antidepressants between the elderly and non-elderly MDD participants.

PMID- 29324371
TI  - Multiple synchronous adenocarcinomas of the small bowel in a young patient: A
      case report.
AB  - INTRODUCTION: Adenocarcinoma of the small bowel is a rare neoplasm presented
      usually in elder patients as a single tumor. Its presentation as multiple tumors
      and in young patients is exceptional and there aren't any guidelines to orient
      its therapy. PRESENTATION OF CASE: We present the rare case of a sixteen-year-old
      woman that presents to the emergency department with an intussusception due to a
      small bowel tumor. The resected specimen showed multiple adenocarcinomas. A
      complete endoscopic and PET-CT study showed other 5 lesions from the duodenum to
      the ileum that were resected. Genetic counseling showed no pathogenic changes.
      The final staging was T2N0M0 and only surveillance was indicated. The patient is
      now 3 years without any recurrence. DISCUSSION: Multiple adenocarcinomas of the
      small bowel are a very infrequent presentation of the disease. Most common risk
      factors include Crohn disease and adenomas. Its presentation is usually vague
      with a delay in its diagnosis. The treatment remains mainly surgical with limited
      use of adjuvant therapy. The most important prognostic factor is lymph node
      involvement with 5-year survival that can range from 3%-60% depending on the
      stage. CONCLUSION: This case represents an exceptional presentation of a very
      rare pathology with few cases described in the literature. There isn't one single
      best study to stage the patient and surgery is still the standard of treatment
      while adjuvant therapies studies are being conducted. The young age and lack of
      predisposing factors or mutations leaves an open field for investigation.

PMID- 29324369
TI  - Early life social stress and resting state functional connectivity in postpartum
      rat anterior cingulate circuits.
AB  - INTRODUCTION: Continued development and refinement of resting state functional
      connectivity (RSFC) fMRI techniques in both animal and clinical studies has
      enhanced our comprehension of the adverse effects of stress on psychiatric
      health. The objective of the current study was to assess both maternal behavior
      and resting state functional connectivity (RSFC) changes in these animals when
      they were dams caring for their own young. It was hypothesized that ECSS exposed
      dams would express depressed maternal care and exhibit similar (same networks),
      yet different specific changes in RSFC (different individual nuclei) than
      reported when they were adult females. METHODS: We have developed an
      ethologically relevant transgenerational model of the role of chronic social
      stress (CSS) in the etiology of postpartum depression and anxiety. Initial fMRI
      investigation of the CSS model indicates that early life exposure to CSS (ECSS)
      induces long term changes in functional connectivity in adult nulliparous female
      F1 offspring. RESULTS: ECSS in F1 dams resulted in depressed maternal care
      specifically during early lactation, consistent with previous CSS studies, and
      induced changes in functional connectivity in regions associated with sensory
      processing, maternal and emotional responsiveness, memory, and the reward
      pathway, with robust changes in anterior cingulate circuits. LIMITATIONS: The
      sample sizes for the fMRI groups were low, limiting statistical power.
      CONCLUSION: This behavioral and functional neuroanatomical foundation can now be
      used to enhance our understanding of the neural etiology of early life stress
      associated disorders and test preventative measures and treatments for stress
      related disorders.

PMID- 29324373
TI  - Abdominal CT-aided diagnosis of acute appendicitis in the presence of mobile
      cecum: A case report.
AB  - INTRODUCTION: A mobile cecum is a frequently encountered congenital anomaly. It
      is important to recognize this atypical position of the cecum as it may interfere
      with an accurate diagnosis of acute appendicitis. PRESENTATION OF CASE: A 48-year
      old man presented with abdominal pain, anorexia, and fever. He had mild lower
      abdominal discomfort, and rebound tenderness in the suprapubic region, but no
      guarding or right lower quadrant findings. Laboratory tests identified an
      elevated white blood cell count (12350 cells/mL) and C-reactive protein level
      (4.56 mg/dL). In view of the clinical picture suggestive of localized
      peritonitis, an abdominal computed tomography (CT) was performed, which revealed
      a caudally located cecum, lying in the pelvis, along with evidence of an acutely
      inflamed appendix. An urgent surgical procedure was performed, which confirmed
      the diagnosis of acute appendicitis accompanying a mobile cecum. DISCUSSION: In
      the presence of a mobile cecum, the clinical findings of acute appendicitis may
      be atypical owing to the abnormal position of the appendix. In such cases, there
      is the possibility of a missed diagnosis. In our case, a CT examination that was
      performed in view of the clinical diagnosis of mild peritonitis aided in
      establishing the diagnosis of acute appendicitis and a mobile cecum. CONCLUSION:
      Anatomical variations of the cecum and the appendix may result in atypical
      presentation of acute appendicitis. A high index of suspicion, and a CT
      examination may be helpful in establishing the diagnosis in such cases.

PMID- 29324372
TI  - Dislocation of a cerebral protection device component during carotid stenting: A
      case report of favorable outcome from conservative management after failure of
      retrieval.
AB  - INTRODUCTION: Cerebral-protection devices (CPDs) are a well-established system
      for reduction of embolic risk in carotid artery angioplasty and stenting (CAS).
      Although rare, adverse events with CPDs are unpredictable and can be associated
      with serious outcomes and iatrogenic sequelae. PRESENTATION OF CASE: We describe
      the unique case of dislocation of a FilterWire EXTM filter loop during right CAS.
      On trying to recapture the CPD filter at the end of the procedure, the filter
      loop suddenly detached from the guidewire and dislocated to the proximal middle
      cerebral artery. Attempted retrieval of the loop failed and the patient developed
      a transient neurological deficit caused by an acute ischemic infarction in the
      lenticular nucleus. No further retrieval attempt was pursued. No further
      dislocation of the loop or clinical event have been reported during the 16-year
      follow up. DISCUSSION: This case reported a favorable outcome of conservative
      management for entrapped material from a CPD after iatrogenic damage from failed
      retrieval. No similar reports are available in the literature, and conservative
      management is generally not a recommended approach because of the potential
      complications. However, rescue retrieval attempts are as well a potential source
      of serious events, and no clear guidelines exist on the management of mechanical
      complications from CPD. CONCLUSION: Entrapment of CPD components constitutes an
      adverse event with no unique solution for risk-free management. The potential
      risks associated with the use of protection devices are still to be fully
      explored, and improving the standard of care and patient safety needs to be a top
      priority.

PMID- 29324374
TI  - Ileal GIST presenting with bacteremia and liver abscess: A case report and review
      of literature.
AB  - INTRODUCTION: Small intestine gastrointestinal stromal tumors can infrequently
      present with intra-abdominal abscess, perforation, obstruction or fistula. Tumor
      small intestine fistula is a rare phenomenon and occurs as a result of GISTs'
      propensity to cause mucosal ulceration. This allows bacteria from the gut to gain
      access to the systemic circulation and predisposes the patient to bacteremia and
      pyogenic liver abscess. PRESENTATION OF CASE: We present a case of a 63-year-old
      female whose initial symptoms included fever, nausea, vomiting and right upper
      quadrant pain. Radiologic studies revealed a liver lesion and an intra-abdominal
      mass containing oral contrast, suggesting involvement of the gastrointestinal
      tract. She was found to have a liver abscess, Streptococcus anginosus bacteremia
      and an ileal GIST that formed a fistula between the tumor and small intestine. We
      performed a surgical resection of the tumor and percutaneous drainage of the
      liver abscess. Imatinib was initiated post operatively and she experienced no
      recurrence, as demonstrated by a surveillance computed tomography scan at 12
      months. CONCLUSION: Findings of a liver lesion in association with a small
      intestine GIST should raise concern for both metastatic disease and a possible
      infectious complication such as a pyogenic liver abscess. If a member of the
      Streptococcus milleri group is isolated in blood cultures, a consideration for
      gastrointestinal malignancy is imperative. This case report reviews a rare
      presentation of an ileal GIST with tumor-intestinal fistula, complicated by liver
      abscess and Streptococcus anginosus bacteremia.

PMID- 29324375
TI  - Cancer in an unexpected site post pouch surgery for familial adenomatous
      polyposis (FAP).
AB  - INTRODUCTION: Familial Adenomatous Polyposis (FAP) is a hereditary condition
      characterized by multiple colorectal adenomatous polyps. FAP is the most common
      adenomatous polyposis syndrome. Restorative proctocolectomy is the most commonly
      performed surgical procedure performed for patients suffering from FAP with
      different options for anastomosis, namely ileorectal anastomosis (IRA) or ileal
      pouch anal anastomosis (IPAA). The occurrence of adenomas is a common finding
      during follow up and surveillance post surgery for these patients. Although there
      are a few cases of carcinoma that were namely at the anal transitional zone
      (ATZ), there are only a few cases of ileal pouch related adenocarcinoma reported.
      This work has been reported in line with the SCARE criteria (Agha et al., 2016)
      [1]. PRESENTATION OF CASE: We report a case of a 34-year-old man diagnosed with
      FAP who underwent proctocolectomy with IPAA, and subsequently referred to our
      center, who, despite appropriate measures and surveillance, developed
      adenocarcinoma in the ileal pouch. DISCUSSION: Restorative proctocolectomy for
      Familial Adenomatous Polyposis (FAP) is the mainstay of treatment. There are
      different surgical options, each with its own set of advantages and
      disadvantages. The most favored option is proctocolectomy with ileal pouch anal
      anastomosis (IPAA) due to because it involves resection of the rectum. Despite
      these interventions, adenomas and/or carcinomas have been reported on follow up
      post surgery. CONCLUSION: Although the risk of developing adenomas or carcinomas
      in the ileal pouch post proctocolectomy with IPAA is low it should not be
      neglected as cancer occurrence or recurrence is unpredictable even with
      appropriate measures.

PMID- 29324376
TI  - Evaluation of Translaryngeal Percutaneous Arytenoid Lateralization (TPAL) in dogs
      with experimentally created laryngeal paralysis.
AB  - The aim of this experimental study was to evaluate the effect of Translaryngeal
      Percutaneous Arytenoid Lateralization (TPAL) in dogs with experimentally created
      laryngeal paralysis. All dogs (n=5) underwent bilateral recurrent laryngeal
      neurectomy before TPAL. Two TPAL suture techniques were evaluated. TPAL
      CranialCaudal (TPAL-CC) was performed first, followed 11 to 14days later by TPAL
      DorsalVentral (TPAL-DV). For both techniques, a mattress suture was placed
      through the arytenoid cartilage via an oral approach. Laryngeal examination was
      performed before, immediately after, and on days 1, 3 and 7 for both TPAL
      techniques. Ipsilateral hemiglottic surface area and the degree of laryngeal
      swelling or reaction to the suture were recorded. Laryngeal tissue was evaluated
      by histopathology at the end of the study. For both TPAL techniques, hemiglottic
      surface area was increased immediately after suture placement (P<0.05). At all
      other times, hemiglottic area was not statistically different from preoperative
      value (P>0.05). TPAL-DV resulted in less laryngeal swelling compared to TPAL-CC.
      Histopathology of the arytenoid cartilage surrounding the mattress suture
      revealed mucosal ulceration and inflammation consistent with the presence of the
      suture material. Both TPAL techniques were effective at lateralizing the
      arytenoid cartilage and significantly increasing hemiglottic surface area
      immediately after suture placement. However, mucosal swelling and loss of tension
      on the mattress suture lead to a decrease in glottic area within 24h. Further
      refinements in suture placement technique are warranted to minimize swelling and
      improve the duration of arytenoid lateralization prior to clinical application.

PMID- 29324377
TI  - Ammonia emissions from paddy fields are underestimated in China.
AB  - Excessive nitrogen (N) fertilizers are often used in China, and a large
      proportion of the N can be lost as ammonia (NH3). However, quantifying the NH3
      emission from paddy fields is always affected by large uncertainties due to
      different measuring methods and other factors such as climate. In this study,
      using a standardized method, we measured the NH3 emissions in three typical
      annual rice cropping systems: single rice, double rice and rotation with other
      crops. The measurements were conducted for 2 years with a total of 3131
      observations across China. Results showed that NH3 emissions accounted for 17.7%
      (14.4-21.0%) of the N applied under current farm practice, which was 33.1% (10.6
      52.6%) higher than previous estimates. Nitrogen application rate was the dominant
      factor influencing NH3 emission rate, which exponentially increased with the N
      fertilizer rate (p < .001). Total NH3 emissions from paddy fields were estimated
      at 1.7 Tg N yr-1 in 2013 in China, several times the amount of N lost through
      leaching or runoff. This suggests that mitigation measures for non-point source
      pollution from cropland should take into account not only the N lost to water,
      but also to air, thereby improving air quality.

PMID- 29324378
TI  - Impact evaluation of environmental factors on respiratory function of asthma
      patients living in urban territory.
AB  - BACKGROUND: Environmental pollution, local climatic conditions and their
      association with the prevalence and exacerbation of asthma are topics of intense
      current medical investigation. MATERIALS AND METHODS: Air pollution in the area
      of Vladivostock was estimated both by the index of emission volumes of "air
      gaseous components" (nitrogen oxide and nitrogen dioxide, formaldehyde, hydrogen
      sulfide, carbon monoxide) in urban atmosphere and by mass spectrometric analysis
      of precipitates in snow samples. A total of 172 local asthma patients (101
      controlled-asthma patients-CAP and 71 non-controlled asthma patients - nCAP) were
      evaluated with the use of spirometry and body plethysmography. Airway obstruction
      reversibility was evaluated with the use of an inhaled bronchodilator. Using
      discriminant analysis the association of environmental parameters with clinical
      indices of asthma patients is explored and thresholds of impact are established.
      RESULTS: CAP presented high sensitivity to large-size suspended air particles and
      to several of the studied climatic parameters. Discriminant analysis showed high
      values of Wilks' lambda index (alpha = 0.69-0.81), which implies limited
      influence of environmental factors on the respiratory parameters of CAP. nCAP
      were more sensitive and susceptible to the majority of the environmental factors
      studied, including air suspended toxic metals particles (Cr, Zn and Ni). Air
      suspended particles showed higher tendency for pathogenicity in nCAP population
      than in the CAP, with a wider range of particle sizes being involved. Dust
      fractions ranging from 0 to 1 MUm and from 50 to 100 MUm were additionally
      implicated compared to CAP group. Considerably lowest thresholds levels of impact
      are calculated for nCAP.

PMID- 29324379
TI  - Associating ambient exposure to fine particles and human fertility rates in
      China.
AB  - BACKGROUND: Adverse effects of ambient fine particles (PM2.5) on sperm quality
      and oocyte fertilization have been identified by previous research. However,
      insufficient human studies tested associations between PM2.5 and decreased
      fertility rates. METHODS: We associated long-term exposure to PM2.5 and county
      level fertility rates reported by 2010 census across China. Exposure assessments
      were based on PM2.5 maps (2009-2010) with a spatial resolution of 0.1 degrees 
      derived from satellite remote sensing data from another published study. We used
      a Poisson regression to examine the relationship between PM2.5 and fertility
      rates with adjustment of potential confounders including county-level
      socioeconomic factors (e.g. sex ratio) and a spatially smoothed trend. RESULTS:
      We found that fertility rates were significantly decreased by 2.0% (95%
      confidence interval: 1.8%, 2.1%) per 10 MUg/m3 increment of PM2.5. We also found
      a geographical variation of the associations. CONCLUSIONS: The study add to
      epidemiological evidences on adverse effects of PM2.5 on fertility rates.

PMID- 29324380
TI  - Estimated individual inhaled dose of fine particles and indicators of lung
      function: A pilot study among Chinese young adults.
AB  - Fine particle (PM2.5)-related lung damage has been reported in most studies
      regarding environmental or personal PM2.5 concentrations. To assess effects of
      personal PM2.5 exposures on lung function, we recruited 20 postgraduate students
      and estimated the individual doses of inhaled PM2.5 based on their
      microenvironmetal PM2.5 concentrations, time-activity patterns and refereed
      inhalation rates. During the period of seven consecutive days in each of the four
      seasons, we repeatedly measured the daily lung function parameters and airway
      inflammation makers such as fractional exhaled nitric oxide (FeNO) as well as
      systemic inflammation markers including interleukin-1beta on the final day. The
      high individual dose (median (IQR)) of inhaled PM2.5 was 957 (948) MUg/day. We
      observed a maximum FeNO increase (9.1% (95%CI: 2.2-15.5)) at lag 0 day, a maximum
      decrease of maximum voluntary ventilation (11.8% (95% CI: 4.6-19.0)) at lag 5 day
      and a maximum interleukin-1beta increase (103% (95% CI: 47-159)) at lag 2 day for
      an interquartile range increase in the individual dose of inhaled PM2.5 during
      the four seasons. Short-term exposure to PM2.5 assessed by the individual dose of
      inhaled PM2.5 was associated with higher airway and systemic inflammation and
      reduced lung function. Further studies are needed to understand better underlying
      mechanisms of lung damage following acute exposure to PM2.5.

PMID- 29324381
TI  - Comparative study of diesel and biodiesel exhausts on lung oxidative stress and
      genotoxicity in rats.
AB  - The contribution of diesel exhaust to atmospheric pollution is a major concern
      for public health, especially in terms of occurrence of lung cancers. The present
      study aimed at addressing the toxic effects of a repeated exposure to these
      emissions in an animal study performed under strictly controlled conditions. Rats
      were repeatedly exposed to the exhaust of diesel engine. Parameters such as the
      presence of a particle filter or the use of gasoil containing rapeseed methyl
      ester were investigated. Various biological parameters were monitored in the
      lungs to assess the toxic and genotoxic effects of the exposure. First, a
      transcriptomic analysis showed that some pathways related to DNA repair and cell
      cycle were affected to a limited extent by diesel but even less by biodiesel. In
      agreement with occurrence of a limited genotoxic stress in the lungs of diesel
      exposed animals, small induction of gamma-H2AX and acrolein adducts was observed
      but not of bulky adducts and 8-oxodGuo. Unexpected results were obtained in the
      study of the effect of the particle filter. Indeed, exhausts collected downstream
      of the particle filter led to a slightly higher induction of a series of genes
      than those collected upstream. This result was in agreement with the formation of
      acrolein adducts and gammaH2AX. On the contrary, induction of oxidative stress
      remained very limited since only SOD was found to be induced and only when rats
      were exposed to biodiesel exhaust collected upstream of the particle filter.
      Parameters related to telomeres were identical in all groups. In summary, our
      results point to a limited accumulation of damage in lungs following repeated
      exposure to diesel exhausts when modern engines and relevant fuels are used. Yet,
      a few significant effects are still observed, mostly after the particle filter,
      suggesting a remaining toxicity associated with the gaseous or nano-particular
      phases.

PMID- 29324382
TI  - Spatial and temporal distribution of antibiotic resistomes in a peri-urban area
      is associated significantly with anthropogenic activities.
AB  - With the rapid development of urbanization and industrialization, the peri-urban
      areas are often the sites for waste dumps, which may exacerbate the occurrence
      and spread of antibiotic resistance from waste to soil bacteria. However, the
      profiles of antibiotic resistomes and the associated factors influencing their
      dissemination in peri-urban areas have not been fully explored. Here, we
      characterized the antibiotic resistance genes (ARGs) in peri-urban arable and
      pristine soils in four seasons at the watershed scale, by using high-throughput
      qPCR. ARGs in peri-urban soils were diverse and abundant, with a total of 222
      genes were detected in the peri-urban soil samples. The arable soil harbored more
      diverse ARGs compared to the pristine soils, and nearly all the ARGs detected in
      the pristine soils were also detected in the farmlands. A random forest
      prediction showed that the overall patterns of ARGs clustered closely with the
      landuse type. Mantel test and partial redundancy analysis indicated that
      bacterial community variation is a major contributor to antibiotic resistome
      alteration. Significant positive correlation was found between the abundance of
      ARGs and mobile genetic elements (MGEs), suggesting potential mobility of ARGs in
      peri-urban areas. Our results extend knowledge of the resistomes compositions in
      peri-urban areas, and suggest that anthropogenic activities driving its spatial
      and temporal distribution.

PMID- 29324383
TI  - The influence of algal organic matter produced by Microcystis aeruginosa on
      coagulation-ultrafiltration treatment of natural organic matter.
AB  - Cyanobacterial bloom causes the release of algal organic matter (AOM), which
      inevitably affects the treatment processes of natural organic matter (NOM). This
      study works on treating micro-polluted surface water (SW) by emerging coagulant,
      namely titanium sulfate (Ti(SO4)2), followed by Low Pressure Ultrafiltration
      (LPUF) technology. In particular, we explored the respective influence of
      extracellular organic matter (EOM) and intracellular organic matter (IOM) on
      synergetic EOM-NOM/IOM-NOM removal, functional mechanisms and subsequent
      filtration performance. Results show that the IOM inclusion in surface water body
      facilitated synergic IOM-NOM composite pollutants removal by Ti(SO4)2, wherein
      loosely-aggregated flocs were produced, resulting in floc cake layer with rich
      porosity and permeability during LPUF. On the contrary, the surface water invaded
      by EOM pollutants increased Ti(SO4)2 coagulation burden, with substantially
      deteriorated both UV254-represented and dissolved organic matter (DOC) removal.
      Corresponded with the weak Ti(SO4)2 coagulation for EOM-NOM removal was the
      resultant serious membrane fouling during LPUF procedure, wherein dense cake
      layer was formed due to the compact structure of flocs. Although the IOM enhanced
      NOM removal with reduced Ti(SO4)2 dose and yielded mitigated membrane fouling,
      larger percentage of irreversible fouling was seen than NOM and EOM-NOM cases,
      which was most likely due to the substances with small molecular weight, such as
      microcystin, adhering in membrane pores. This research would provide theoretical
      basis for dose selection and process design during AOM-NOM water treatment.

PMID- 29324384
TI  - Flame retardants in UK furniture increase smoke toxicity more than they reduce
      fire growth rate.
AB  - This paper uses fire statistics to show the importance of fire toxicity on fire
      deaths and injuries, and the importance of upholstered furniture and bedding on
      fatalities from unwanted fires. The aim was to compare the fire hazards (fire
      growth and smoke toxicity) using different upholstery materials. Four
      compositions of sofa-bed were compared: three meeting UK Furniture Flammability
      Regulations (FFR), and one using materials without flame retardants intended for
      the mainland European market. Two of the UK sofa-beds relied on chemical flame
      retardants to meet the FFR, the third used natural materials and a technical
      weave in order to pass the test. Each composition was tested in the bench-scale
      cone calorimeter (ISO 5660) and burnt as a whole sofa-bed in a sofa configuration
      in a 3.4 * 2.25 * 2.4 m3 test room. All of the sofas were ignited with a No. 7
      wood crib; the temperatures and yields of toxic products are reported. The sofa
      beds containing flame retardants burnt somewhat more slowly than the non-flame
      retarded EU sofa-bed, but in doing so produced significantly greater quantities
      of the main fire toxicants, carbon monoxide and hydrogen cyanide. Assessment of
      the effluents' potential to incapacitate and kill is provided showing the two UK
      flame retardant sofa-beds to be the most dangerous, followed by the sofa-bed made
      with European materials. The UK sofa-bed made only from natural materials
      (Cottonsafe(r)) burnt very slowly and produced very low concentrations of toxic
      gases. Including fire toxicity in the FFR would reduce the chemical flame
      retardants and improve fire safety.

PMID- 29324385
TI  - Ameliorative effects of selenium on arsenic-induced cytotoxicity in PC12 cells
      via modulating autophagy/apoptosis.
AB  - Arsenic is well known toxicant responsible for human diseases including cancers.
      On the other hand, selenium is an essential trace element with significant
      chemopreventive effects, anticancer potentials and antioxidant properties.
      Although previous studies have reported antagonism/synergism between arsenic and
      selenium in biological systems, the biomolecular mechanism/s is still
      inconclusive. Therefore, to elucidate the molecular phenomena in cellular level,
      we hypothesized that co-exposure of selenium with arsenic may have suppressive
      effects on arsenic-induced cytotoxicity. We found that selenium in co-exposure
      with arsenic increases cell viability, and suppresses oxidative stress induced by
      arsenic in PC12 cells. Consequently, DNA fragmentation due to arsenic exposure
      was also reduced by arsenic and selenium co-exposure. Furthermore, western blot
      analyses revealed that simultaneous exposure of both metals significantly
      inhibited autophagy which further suppressed apoptosis through positively
      regulation of key proteins; p-mTOR, p-Akt, p-Foxo1A, p62, and expression of
      ubiquitin, Bax, Bcl2, NFkB, and caspases 3 and 9, although those are negatively
      regulated by arsenic. In addition, reverse transcriptase PCR analysis confirmed
      the involvement of caspase cascade in cell death process induced by arsenic and
      subsequent inhibition by co-exposure of selenium with arsenic. The cellular
      accumulation study of arsenic in presence/absence of selenium via inductively
      coupled plasma mass spectrometry confirmed that selenium effectively retarded the
      uptake of arsenic in PC12 cells. Finally, these findings imply that selenium is
      capable to modulate arsenic-induced intrinsic apoptosis pathway via enhancement
      of mTOR/Akt autophagy signaling pathway through employing antioxidant potentials
      and through inhibiting the cellular accumulation of arsenic in PC12 cells.

PMID- 29324386
TI  - Effects of two ecological earthworm species on atrazine degradation performance
      and bacterial community structure in red soil.
AB  - Vermicomposting is an effective and environmentally friendly approach for
      eliminating soil organic contamination. Atrazine is one of the most commonly
      applied triazinic herbicides and frequently detected in agricultural soils. This
      study investigated the roles and mechanisms of two earthworm species (epigeic
      Eisenia foetida and endogeic Amynthas robustus) in microbial degradation of
      atrazine. Both earthworms accelerated atrazine degradation performance from 39.0%
      in sterile soils to 94.9%-95.7%, via neutralizing soil pH, consuming soil humus,
      altering bacterial community structure, enriching indigenous atrazine degraders
      and excreting the intestinal atrazine-degrading bacteria. Rhodoplanes and
      Kaistobacter were identified as soil indigenous degraders for atrazine
      mineralization and stimulated by both earthworm species. A. robustus excreted the
      intestinal Cupriavidus and Pseudomonas, whereas Flavobacterium was released by E.
      foetida. This study provides a comprehensive understanding of the distinct
      effects of two earthworm species on soil microbial community and atrazine
      degradation, offering technical supports to apply vermicomposting in effective
      soil bioremediation.

PMID- 29324387
TI  - A novel photoactive and three-dimensional stainless steel anode dramatically
      enhances the current density of bioelectrochemical systems.
AB  - This study reports a high-performance 3D stainless-steel photoanode (3D SS
      photoanode) for bioelectrochemical systems (BESs). The 3D SS photoanode consists
      of 3D carbon-coated SS felt bioactive side and a flat alpha-Fe2O3-coated SS plate
      photoactive side. Without light illumination, the electrode reached a current
      density of 26.2 +/- 1.9 A m-2, which was already one of the highest current
      densities reported thus far. Under illumination, the current density of the
      electrode was further increased to 46.5 +/- 2.9 A m-2. The mechanism of the photo
      enhanced current production can be attributed to the reduced charge-transfer
      resistance between electrode surface and the biofilm with illumination. It was
      also found that long-term light illumination can enhance the biofilm formation on
      the 3D SS photoanode. These findings demonstrate that using the synergistic
      effect of photocatalysis and microbial electrocatalysis is an efficient way to
      boost the current production of the existing high-performance 3D anodes for BESs.

PMID- 29324388
TI  - Toxicity of surface-modified copper oxide nanoparticles in a mouse macrophage
      cell line: Interplay of particles, surface coating and particle dissolution.
AB  - The rapid dissolution of copper oxide (CuO) nanoparticles (NPs) with release of
      ions is thought to be one of the main factors modulating their toxicity. Here we
      assessed the cytotoxicity of a panel of CuO NPs (12 nm +/- 4 nm) with different
      surface modifications, i.e., anionic sodium citrate (CIT) and sodium ascorbate
      (ASC), neutral polyvinylpyrrolidone (PVP), and cationic polyethylenimine (PEI),
      versus the pristine (uncoated) NPs, using a murine macrophage cell line
      (RAW264.7). Cytotoxicity, reactive oxygen species (ROS) production, and cellular
      uptake were assessed. The cytotoxicity results were analyzed by the benchmark
      dose (BMD) method and the NPs were ranked based on BMD20 values. The PEI-coated
      NPs were found to be the most cytotoxic. Despite the different properties of the
      coating agents, NP dissolution in cell medium was only marginally affected by
      surface modification. Furthermore, CuCl2 (used as an ion control) elicited
      significantly less cytotoxicity when compared to the CuO NPs. We also observed
      that the antioxidant, N-acetylcysteine, failed to protect against the
      cytotoxicity of the uncoated CuO NPs. Indeed, the toxicity of the surface
      modified CuO NPs was not directly linked to particle dissolution and subsequent
      Cu burden in cells, nor to cellular ROS production, although CuO-ASC NPs, which
      were found to be the least cytotoxic, yielded lower levels of ROS in comparison
      to pristine NPs. Hierarchical cluster analysis suggested, instead, that the
      toxicity in the current in vitro model could be explained by synergistic
      interactions between the NPs, their dissolution, and the toxicity of the coating
      agents.

PMID- 29324389
TI  - Dynamic validation of online applied and surrogate-based models for tertiary
      ozonation on pilot-scale.
AB  - New robust correlation models for ozonation, based on UVA254 and fluorescence
      surrogate parameters and developed considering kinetic information, have been
      applied at pilot-scale. This model framework is validated with the aim for
      operators to control the ozone dose for the removal of trace organic contaminants
      (TrOCs) in effluents from full-scale municipal wastewater treatment plants. The
      inflected correlation model between DeltaTrOCs and the surrogates predicts the
      removal of TrOCs (based on statistical evidence) solely using the 2nd order
      reaction rate constant with ozone (kO3) and in a more adequate manner than
      similar single correlation models. This allows the use of this new model for
      current and future TrOCs under investigation which is highly interesting when
      imposed discharge limits might include more and other TrOCs in future. The use of
      UVA254 might be preferable at the current timing for online monitoring of TrOC
      abatement as the model showed a good predictive power (based on statistical
      evidence and visual confirmation). Reliable online sensors are more widespread
      (and commercially) available compared to fluorescence sensors which are still
      under development, with the exception of a few examples. Nevertheless, the data
      processing of the fluorescence signals, isolating the different intensities
      associated with moieties reacting similarly to ozone might even increase the
      predictive power, given the lower degree of interference (i.e. less scattering).

PMID- 29324390
TI  - NFAT-1 hyper-activation by methionine enkephalin (MENK) significantly induces
      cell apoptosis of rats C6 glioma in vivo and in vitro.
AB  - The aim of the work was to investigate the effect and possible mechanism of MENK
      on the growth of rat C6 glioma in vivo or in vitro. Our findings showed that MENK
      could inhibit the growth of rat C6 glioma, prolong median survival times in tumor
      bearing rats, and induce glioma cell apoptosis. Moreover, MENK could increase the
      activities of caspase-3, caspase-8 and caspase-9. It also increased the
      expression of Fas, FasL, Bax, while decreased the expression of Bcl-2. We further
      confirmed that MENK could increase opioid receptors MOR and DOR expressions, Ca2+
      influx into the cytoplasm, and a substantial increase of NFAT1accumulation in the
      nuclei in C6 glioma cell. When we specifically knocked down NFAT1, there was no
      effect of MENK on the cell viability and FasL up-regulation in NFAT1 knocked-down
      cell. These results demonstrate that MENK could bind to opioid receptors MOR and
      DOR on C6 glioma cells and trigger a Ca2+ influx into the cytoplasm, resulting in
      translocation of NFAT1 into the nucleus. The hyper-activation of NFAT1 may
      regulate transcription of downstream gene, such as FasL, and induce apoptosis of
      rat C6 glioma cells.

PMID- 29324391
TI  - siRNA-mediated c-Rel knockdown ameliorates collagen-induced arthritis in mice.
AB  - Previous studies have shown that inflammatory mediators involved in the
      development of rheumatoid arthritis (RA) are regulated by the Rel/nuclear factor
      kappaB (Rel/NF-kappaB) transcription factor family. c-Rel, a member of the Rel/NF
      kappaB family that is preferentially expressed by immune cells, is a risk factor
      for several inflammatory diseases including RA. In the current study, we
      investigated whether targeting c-Rel can be used to treat collagen-induced
      arthritis, an animal model for RA. c-Rel specific siRNA (siRel) delivered by
      nanoparticles was used to knockdown the expression of c-Rel. Our results showed
      that siRel treatment significantly ameliorated collagen-induced arthritis.
      Further study revealed that c-Rel expression in the dendritic cells and
      macrophages from mice treated with siRel was significantly down-regulated.
      Consistent with the phenotypical result, the expression of inflammatory cytokines
      TNF-alpha, IL-1beta, IL-6, IL-12 and IL-23 by peritoneal macrophages and
      splenocytes were significantly decreased. In addition, attenuated systemic and
      collagen-specific Th1 and Th17 immune responses were observed. Furthermore, we
      found that the expression of inflammatory cytokines was significantly down
      regulated and the infiltration of CD3+ T cells and F4/80+ macrophages was
      markedly reduced in hind paws of mice treated with siRel. Collectively, our study
      provides strong evidence that siRNA-mediated c-Rel knockdown can suppress the
      development of collagen-induced arthritis in mice. Therefore, blocking c-Rel may
      represent an attracting strategy for the treatment of human rheumatoid arthritis.

PMID- 29324392
TI  - Abnormal RNA splicing and genomic instability after induction of DNMT3A mutations
      by CRISPR/Cas9 gene editing.
AB  - DNA methyltransferase 3A (DNMT3A) mediates de novo DNA methylation. Mutations in
      DNMT3A are associated with hematological malignancies, most frequently acute
      myeloid leukemia. DNMT3A mutations are hypothesized to establish a pre-leukemic
      state, rendering cells vulnerable to secondary oncogenic mutations and malignant
      transformation. However, the mechanisms by which DNMT3A mutations contribute to
      leukemogenesis are not well-defined. Here, we successfully created four DNMT3A
      mutated K562 cell lines with frameshift mutations resulting in truncated DNMT3A
      proteins. DNMT3A-mutated cell lines exhibited significantly impaired growth and
      increased apoptotic activity compared to wild-type (WT) cells. Consistent with
      previous studies, DNMT3A-mutated cells displayed impaired differentiation
      capacity. RNA-seq was used to compare transcriptomes of DNMT3A-mutated and WT
      cells; DNMT3A ablation resulted in downregulation of genes involved in
      spliceosome function, causing dysfunction of RNA splicing. Unexpectedly, we
      observed DNMT3A-mutated cells to exhibit marked genomic instability and an
      impaired DNA damage response compared to WT. CRISPR/Cas9-mediated DNMT3A-mutated
      K562 cells may be used to model effects of DNMT3A mutations in human cells. Our
      findings implicate aberrant splicing and induction of genomic instability as
      potential mechanisms by which DNMT3A mutations might predispose to malignancy.

PMID- 29324393
TI  - Changing students' perceptions of the homeless: A community service learning
      experience.
AB  - The homeless are an underserved, local vulnerable population that can benefit
      from a service learning clinical practicum experience for baccalaureate prepared
      nursing students. Negative attitudes and disrespect among healthcare workers has
      been identified by the homeless as a barrier to healthcare. A service learning
      experience with a vulnerable population has been shown to change nursing
      students' attitudes and beliefs. A large university in a southern city partnered
      with a community based organization that provided services to the homeless to
      educate senior nursing students in a service learning experience. The goal of
      this project was to examine attitudes and perceptions of nursing students toward
      the homeless population before and after participation in a service learning
      clinical practicum experience. This case study utilized a pre and post experience
      questionnaire to collect qualitative data for the purposes of the project. The
      findings revealed students demonstrated a decrease in fear, an increase in
      empathy, and a deeper understanding of the advocacy role of nurses for people
      experiencing homelessness. Nurse educators are challenged to engage students with
      vulnerable populations to change the attitudes and perceptions for improvement in
      the overall health of communities served worldwide. Partnerships and service
      learning experiences can benefit all.

PMID- 29324394
TI  - Effects of ocean acidification on copepods.
AB  - Ocean acidification (OA) leads to significant changes in seawater carbon
      chemistry, broadly affects marine organisms, and considered as a global threat to
      the fitness of marine ecosystems. Due to the crucial role of copepods in marine
      food webs of transferring energy from primary producers to higher trophic levels,
      numerous studies have been conducted to examine the impacts of OA on biological
      traits of copepods such as growth and reproduction. Under OA stress, the copepods
      demonstrated species-specific and stage-dependent responses. Notably, different
      populations of the same copepod species demonstrated different sensitivities to
      the increased pCO2. In copepods, the deleterious effects of OA are also
      reinforced by other naturally occurring co-stressors (e.g., thermal stress, food
      deprivation, and metal pollution). Given that most OA stress studies have focused
      on the effects of short-term exposure (shorter than a single generation),
      experiments using adults might have underestimated the damaging effects of OA and
      the long-term multigenerational exposure to multiple stressors (e.g., increased
      pCO2 and food shortage) will be required. Particularly, omics-based technologies
      (e.g., genomics, proteomics, and metabolomics) will be helpful to better
      understand the underlying processes behind biological responses (e.g., survival,
      development, and offspring production) at the mechanistic level which will
      improve our predictions of the responses of copepods to climate change stressors
      including OA.

PMID- 29324395
TI  - Effects of lanthanum on Microcystis aeruginosa: Attention to the changes in
      composition and content of cellular microcystins.
AB  - Algal blooms threaten human health and aquatic ecosystem through the production
      of microcystins (MCs) by toxic strains. The accumulation of rare earth elements
      (REEs) in water affects the growth and physiological activities of algae.
      However, whether or how REEs affect cellular microcystins (MCs) is largely
      unknown. In this study, the effects of lanthanum ion [La(III)], a type of REE, on
      the MCs in Microcystis aeruginosa were investigated, and the mechanism of the
      effect was analyzed using ecological stoichiometry. The different concentrations
      of La(III) were selected to correlate environmental pollution status. Low-dose
      La(III) (0.2, 2.0, and 4.0 MUM) exposure increased the total content of MCs and
      the percentage contents of microcystin-YR (MC-YR) and microcystin-LW (MC-LW) and
      decreased the percentage content of microcystin-LR (MC-LR). High-dose La(III)
      (8.0, 20, 40, and 60 MUM) exposure decreased the total content of the MCs,
      increased the percentage content of MC-LR, and decreased the percentage contents
      of MC-YR and MC-LW. The changes in the total MCs content were positively
      associated with the ratios of C:P and N:P in algal cells. The composition of MCs
      was dependent on the ratio of C:N in algal cells; for example, the percentage
      content of MC-LR decreased and the percentage content of MC-YR and MC-LW
      increased as the ratio of C:N in algal cells increased. In conclusion, La(III)
      could affect the content and composition of MCs via changes in the growth and
      chlorophyll-a content of Microcystis aeruginosa, and these effects depended on
      the ratios of C:P, N:P, and C:N in Microcystis aeruginosa. Such changes may
      influence the toxicity of Microcystis blooms. The results provides a new insight
      into the mechanism of REEs effects on algal toxins and provide references for
      evaluating environmental risks of REEs pollution in aquatic ecosystems.

PMID- 29324396
TI  - Cyberchondria: Overlap with health anxiety and unique relations with impairment,
      quality of life, and service utilization.
AB  - Cyberchondria refers to a clinical phenomenon in which repeated Internet searches
      regarding medical information result in excessive concerns about physical health.
      Cyberchondria is positively associated with symptoms of health anxiety, though it
      remains unclear as to whether cyberchondria poses a unique public burden. The
      current study replicated previous findings regarding the relationship between
      cyberchondria and health anxiety, and extended those findings to examine the
      extent to which health anxiety and cyberchondria may be differentially associated
      with public health outcomes, including impairment, quality of life, and service
      utilization. Community participants (N = 462) recruited via online crowdsourcing
      completed a battery of self-report questionnaires assessing cyberchondria, health
      anxiety, and measures of public health outcomes, including the WHOQOL and SDS.
      Bifactor latent variable modeling indicated that cyberchondria was closely
      related to, yet importantly distinct from, health anxiety. Moreover, when
      accounting for overlap with health anxiety, cyberchondria was associated with
      increased functional impairment and healthcare utilization. Results provide
      further support for the identification of cyberchondria as a distinct set of
      clinical symptoms that may pose a significant public health burden. Future
      research should determine ways in which to treat and/or prevent symptoms.

PMID- 29324397
TI  - Serum levels of cortisol, dehydroepiandrosterone, and oxytocin in children with
      attention-deficit/hyperactivity disorder combined presentation with and without
      comorbid conduct disorder.
AB  - The present study aimed to investigate serum cortisol, dehydroepiandrosterone
      (DHEA), and oxytocin levels of children with attention-deficit/hyperactivity
      disorder (ADHD) combined presentation and those diagnosed with ADHD combined
      presentation and coexisting conduct disorder. A total of 74 drug-naive children
      with ADHD combined presentation alone, 32 children with ADHD combined
      presentation + conduct disorder, and 42 healthy controls were included. The
      severities of ADHD and conduct disorder symptoms were assessed via parent- and
      teacher-rated questionnaires. The severity of aggression, anxiety, and depression
      symptoms of the children were assessed by the self-report inventories.
      Independent of potential confounders, including age, sex, pubertal stage, and
      severity of depression and anxiety, serum oxytocin levels of the ADHD combined
      presentation + conduct disorder group were significantly lower than those of both
      the ADHD combined presentation alone and control groups. There was also a trend
      for the ADHD combined presentation + conduct disorder group to show lower serum
      DHEA levels than that of the ADHD combined presentation alone group. However,
      serum cortisol levels did not show significant alterations among the groups.
      These findings suggest that oxytocin and DHEA may play a role in the
      pathophysiology of conduct disorder, at least in the presence of ADHD combined
      presentation.

PMID- 29324398
TI  - Epilepsy in patients with pineal gland cyst.
AB  - OBJECTIVE: The aim of the study is to describe types of epileptic seizures in
      patients with pineal gland cyst (PGC) and their outcome during follow up period
      (6-10 years). We wanted to determine whether patients with epilepsy differ in PGC
      volume and compression of the PGC on surrounding brain structures compared to
      patients with PGC, without epilepsy. PATIENTS AND METHODS: We analyzed
      prospectivelly 92 patients with PGC detected on magnetic resonance (MR) of the
      brain due to various neurological symptoms during the period 2006-2010. Data on
      described compression of the PGC on surrounding brain structures and size of the
      PGC were collected. RESULTS: 29 patients (16 women, 13 men), mean age 21.17 years
      had epilepsy and PGC (epilepsy group). 63 patients (44 women, 19 men), mean age
      26.97 years had PGC without epilepsy (control group). Complex partial seizures
      were present in 8 patients, complex partial seizures with secondary
      generalization in 8 patients, generalized tonic clonic seizures (GTCS) in 10 and
      absance seizures in 3 patients. Mean PGC volume in epilepsy group was 855.93 mm3,
      in control group 651.59 mm3. There was no statistically significant difference
      between epilepsy and control group in PGC volume. Compression of PGC on
      surrounding brain structures was found in 3/29 patients (10.34%) in epilepsy
      group and in 11/63 patients (17.46%) in control group with no statistically
      significant difference between epilepsy and control group. All patients with
      epilepsy were put on antiepileptic therapy (AET). During the follow up period, 23
      patients (79.31%) were seizure free, 3 patients (13.04%) had reduction in seizure
      frequency, whereas 3 patients had no improvement in seizure frequency. Two
      patients from epilepsy group and 3 patients from control group were operated with
      histologically confirmed diagnosis of PGC in 4, and pinealocytoma in 1 patient.
      CONCLUSIONS: In patients with PGC, epileptic seizures were classified as: complex
      partial seizures (with or without secondary generalization), GTCS and absance
      seizures. All patients were put on AET. During follow up period 79.31% patients
      were seizure free. There was no difference in PGC volume, nor in described
      compression of the PGC on surrounding brain structures between epilepsy and
      control group. Based on our findings, pathomechanism of epileptic seizures in
      patients with PGC cannot be attributable solely to PGC volume or described
      compression on surrounding brain structures based on MRI findings.

PMID- 29324399
TI  - Primary intracranial leiomyosarcoma in an immunocompetent patient: Case report
      and review of the literature.
AB  - Primary leiomyosarcoma is a rare tumor in the CNS, with few reported cases. Here,
      we describe a case of a primary intracranial leiomyosarcoma of the tentorium
      cerebelli. A 43-year-old woman presented with headache, acute vision loss, and
      difficulty speaking. MRI revealed a large heterogeneous-enhancing occipital mass,
      which was subsequently resected and diagnosed as a primary intracranial
      leiomyosarcoma. The patient went onto adjuvant radiotherapy delivering 60 Gy in
      30 fractions. These tumors are exceedingly rare in immunocompetent individuals.
      We reviewed the 16 cases that have been reported in the literature. Surgical
      resection was the most common treatment (92%) with 53% receiving adjuvant
      radiation. There currently is no standard treatment regimen for intracranial
      leiomyosarcomas. Additional case reports that include descriptive treatment
      approaches with patient outcomes may help ascertain the best approach to treating
      these malignancies.

PMID- 29324400
TI  - Determination of atomic positions from time resolved high resolution transmission
      electron microscopy images.
AB  - For many reaction processes, such as catalysis, phase transformations,
      nanomaterial synthesis etc., nanoscale observations at high spatial (sub
      nanometer) and temporal (millisecond) resolution are required to characterize and
      comprehend the underlying factors that favor one reaction over another. The
      combination of such spatial and temporal resolution (up to 600 us), while rich in
      information, produces a large number of snapshots, each of which must be analyzed
      to obtain the structural (and thereby chemical) information. Here we present a
      methodology for automated quantitative measurement of real-time atomic position
      fluctuations in a nanoparticle. We leverage a combination of several image
      processing algorithms to precisely identify the positions of the atomic columns
      in each image. A geometric model is then used to measure the time-evolution of
      distances and angles between neighboring atomic columns to identify different
      phases and quantify local structural fluctuations. We apply this technique to
      determine the atomic-level fluctuations in the relative fractions of metal and
      metal-carbide phases in a cobalt catalyst nanoparticle during single-walled
      carbon nanotube (SWCNT) growth. These measurements provided a means to obtain the
      number of carbon atoms incorporated into and released from the catalyst particle,
      thereby helping resolve carbon reaction pathways during SWCNT growth. Further we
      demonstrate the use of this technique to measure the reaction kinetics of iron
      oxide reduction. Apart from reducing the data analysis time, the statistical
      approach allows us to measure atomic distances with sub-pixel resolution. We show
      that this method can be applied universally to measure atomic positions with a
      precision of 0.01 nm from any set of atomic-resolution video images. With the
      advent of high time-resolution direct detection cameras, we anticipate such
      methods will be essential in addressing the metrology problem of quantifying
      large datasets of time-resolved images in future.

PMID- 29324402
TI  - C-FSCV: Compressive Fast-Scan Cyclic Voltammetry for Brain Dopamine Recording.
AB  - This paper presents a novel compressive sensing framework for recording brain
      dopamine levels with fast-scan cyclic voltammetry (FSCV) at a carbon-fiber
      microelectrode. Termed compressive FSCV (C-FSCV), this approach compressively
      samples the measured total current in each FSCV scan and performs basic FSCV
      processing steps, e.g., background current averaging and subtraction, directly
      with compressed measurements. The resulting background-subtracted faradaic
      currents, which are shown to have a block-sparse representation in the discrete
      cosine transform domain, are next reconstructed from their compressively sampled
      counterparts with the block sparse Bayesian learning algorithm. Using a
      previously recorded dopamine dataset, consisting of electrically evoked signals
      recorded in the dorsal striatum of an anesthetized rat, the C-FSCV framework is
      shown to be efficacious in compressing and reconstructing brain dopamine dynamics
      and associated voltammograms with high fidelity (correlation coefficient, ),
      while achieving compression ratio, CR, values as high as ~ 5. Moreover, using
      another set of dopamine data recorded 5 minutes after administration of
      amphetamine (AMPH) to an ambulatory rat, C-FSCV once again compresses (CR = 5)
      and reconstructs the temporal pattern of dopamine release with high fidelity ( ),
      leading to a true-positive rate of 96.4% in detecting AMPH-induced dopamine
      transients.

PMID- 29324401
TI  - Unblinded, randomized multicenter trial comparing lamotrigine and valproate
      combination with controlled-release carbamazepine monotherapy as initial drug
      regimen in untreated epilepsy.
AB  - PURPOSE: To compare controlled-release carbamazepine monotherapy (CBZ-CR) with
      lamotrigine and valproate combination therapy (LTG + VPA) in equivalent total
      drug load, as initial drug regimen in untreated patients with partial and/or
      generalized tonic-clonic seizures (GTCS). METHODS: This unblinded, randomized, 60
      week superiority trial recruited patients having two or more unprovoked seizures
      with at least one seizure during previous three months. After randomization into
      CBZ-CR or LTG + VPA, patients entered into eight-week titration phase (TP),
      followed by 52-week maintenance phase (MP). Median doses of CBZ-CR and LTG + VPA
      were 600 mg/day and 75 mg/day + 500 mg/day, respectively. Primary outcome measure
      was completion rate (CR), a proportion of patients who have completed the 60-week
      study as planned. Secondary efficacy measures included seizure-free rate (SFR)
      for 52-week of MP and time to first seizure (TTFS) during MP. RESULTS: Among 207
      randomized patients, 202 underwent outcome analysis (104 in CBZ-CR, 98 in LTG +
      VPA). CR was 62.5% in CBZ-CR and 65.3% in LTG + VPA (p = 0.678). SFR during MP
      was higher in LTG + VPA (64.1%) than CBZ-CR (47.8%) (P = 0.034). TTFS was shorter
      with CBZ-CR (p = 0.041). Incidence of adverse effects (AEs) were 57.7% in CBZ-CR
      and 60.2% in LTG + VPA and premature drug withdrawal rates due to AEs were 12.5%
      and 7.1%, respectively, which were not significantly different. CONCLUSION: CR
      was comparable between LTG + VPA and CBZ-CR, however, both SFR for 52-week MP and
      TTFS during MP were in favor of LTG + VPA than CBZ-CR. The study suggested that
      LTG + VPA can be an option as initial drug regimen for untreated patients with
      partial seizures and/or GTCS except for women of reproductive age.

PMID- 29324403
TI  - Performance of Brain-Computer Interfacing Based on Tactile Selective Sensation
      and Motor Imagery.
AB  - A large proportion of users do not achieve adequate control using current non
      invasive brain-computer interfaces (BCIs). This issue has being coined "BCI
      Illiteracy" and is observed among different BCI modalities. Here, we compare the
      performance and the BCI-illiteracy rate of a tactile selective sensation (SS) and
      motor imagery (MI) BCI, for a large subject samples. We analyzed 80 experimental
      sessions from 57 subjects with two-class SS protocols. For SS, the group average
      performance was 79.8 +/- 10.6%, with 43 out of the 57 subjects (75.4%) exceeding
      the 70% BCI-illiteracy threshold for left- and right-hand SS discrimination. When
      compared with previous results, this tactile BCI outperformed all other tactile
      BCIs currently available. We also analyzed 63 experimental sessions from 43
      subjects with two-class MI BCI protocols, where the group average performance was
      77.2 +/- 13.3%, with 69.7% of the subjects exceeding the 70% performance
      threshold for left- and right-hand MI. For within-subject comparison, the 24
      subjects who participated to both the SS and MI experiments, the BCI performance
      was superior with SS than MI especially in beta frequency band (p < 0.05), with
      enhanced R2 discriminative information in the somatosensory cortex for the SS
      modality. Both SS and MI showed a functional dissociation between lower alpha ([8
      10] Hz) and upper alpha ([10 13] Hz) bands, with BCI performance significantly
      better in the upper alpha than the lower alpha (p < 0.05) band. In summary, we
      demonstrated that SS is a promising BCI modality with low BCI illiteracy issue
      and has great potential in practical applications reaching large population.

PMID- 29324404
TI  - Optimization-Based Contact Fault Alleviation in Deep Brain Stimulation Leads.
AB  - Deep brain stimulation (DBS) is a neurosurgical treatment in, e.g., Parkinson's
      Disease. Electrical stimulation in DBS is delivered to a certain target through
      electrodes implanted into the brain. Recent developments aiming at better
      stimulation target coverage and lesser side effects have led to an increase in
      the number of contacts in a DBS lead as well as higher hardware complexity. This
      paper proposes an optimization-based approach to alleviation of the fault impact
      on the resulting therapeutical effect in field steering DBS. Faulty contacts
      could be an issue given recent trends of increasing number of contacts in DBS
      leads. Hence, a fault detection/alleviation scheme, such as the one proposed in
      this paper, is necessary ensure resilience in the chronic stimulation. Two
      alternatives are considered and compared with the stimulation prior to the fault:
      one using higher amplitudes on the remaining contacts and another with
      alleviating contacts in the neighborhood of the faulty one. Satisfactory
      compensation for a faulty contact can be achieved in both ways. However, to
      designate alleviating contacts, a model-based optimization procedure is
      necessary. Results suggest that stimulating with more contacts yields
      configurations that are more robust to contact faults, though with reduced
      selectivity.

PMID- 29324406
TI  - A Novel Multi-Class EEG-Based Sleep Stage Classification System.
AB  - Sleep stage classification is one of the most critical steps in effective
      diagnosis and the treatment of sleep-related disorders. Visual inspection
      undertaken by sleep experts is a time-consuming and burdensome task. A computer
      assisted sleep stage classification system is thus essential for both sleep
      related disorders diagnosis and sleep monitoring. In this paper, we propose a
      system to classify the wake and sleep stages with high rates of sensitivity and
      specificity. The EEG signals of 25 subjects with suspected sleep-disordered
      breathing, and the EEG signals of 20 healthy subjects from three data sets are
      used. Every EEG epoch is decomposed into eight subband epochs each of which has a
      frequency band pertaining to one EEG rhythm (i.e., delta, theta, alpha, sigma,
      beta 1, beta 2, gamma 1, or gamma 2). Thirteen features are extracted from each
      subband epoch. Therefore, 104 features are totally obtained for every EEG epoch.
      The Kruskal-Wallis test is used to examine the significance of the features. Non
      significant features are discarded. The minimal-redundancy-maximal-relevance
      feature selection algorithm is then used to eliminate redundant and irrelevant
      features. The features selected are classified by a random forest classifier. To
      set the system parameters and to evaluate the system performance, nested 5-fold
      cross-validation and subject cross-validation are performed. The performance of
      our proposed system is evaluated for different multi-class classification
      problems. The minimum overall accuracy rates obtained are 95.31% and 86.64% for
      nested 5-fold and subject cross-validation, respectively. The system performance
      is promising in terms of the accuracy, sensitivity, and specificity rates
      compared with the ones of the state-of-the-art systems. The proposed system can
      be used in health care applications with the aim of improving sleep stage
      classification.

PMID- 29324405
TI  - Determination of Nerve Fiber Diameter Distribution From Compound Action
      Potential: A Continuous Approach.
AB  - When a signal is initiated in the nerve, it is transmitted along each nerve fiber
      via an action potential (called single fiber action potential (SFAP)) which
      travels with a velocity that is related with the diameter of the fiber. The
      additive superposition of SFAPs constitutes the compound action potential (CAP)
      of the nerve. The fiber diameter distribution (FDD) in the nerve can be computed
      from the CAP data by solving an inverse problem. This is usually achieved by
      dividing the fibers into a finite number of diameter groups and solve a
      corresponding linear system to optimize FDD. However, number of fibers in a nerve
      can be measured sometimes in thousands and it is possible to assume a continuous
      distribution for the fiber diameters which leads to a gradient optimization
      problem. In this paper, we have evaluated this continuous approach to the
      solution of the inverse problem. We have utilized an analytical function for SFAP
      and an assumed a polynomial form for FDD. The inverse problem involves the
      optimization of polynomial coefficients to obtain the best estimate for the FDD.
      We have observed that an eighth order polynomial for FDD can capture both
      unimodal and bimodal fiber distributions present in vivo, even in case of noisy
      CAP data. The assumed FDD distribution regularizes the ill-conditioned inverse
      problem and produces good results.

PMID- 29324407
TI  - Head Motion and Head Gesture-Based Robot Control: A Usability Study.
AB  - The assistive robot system adaptive head motion control for user-friendly support
      (AMiCUS) has been developed to increase the autonomy of motion impaired people.
      The six degrees of freedom robot arm with gripper is controlled with head motion
      and head gestures only, so especially tetraplegics benefit from collaboration
      with AMiCUS. In this paper, a usability study with a total number of 30 subjects
      was conducted to validate the AMiCUS interaction technology and design. 24 able
      bodied subjects of demographically diverse groups and 6 tetraplegics participated
      in this paper. All subjects performed different pick and place tasks by
      controlling AMiCUS. The evaluation of the interaction design was carried out
      subjectively with a questionnaire as well as objectively by measurement of time,
      completion rate, and number of trials for correct head gesture performance. The
      influence of several factors like age, sex, motion impairment, and previous
      experience on head motion-based human-robot interaction was analyzed. The
      interaction design has been proven successful in laboratory environment and
      assessed overall positive by the subjects. The results of the presented paper
      confirm the usability of the assistive robot AMiCUS. AMiCUS has the potential to
      benefit tetraplegics by improving their independence in activities of daily
      living and adapted workplaces.

PMID- 29324408
TI  - Assessing Dynamic Balance Performance During Exergaming Based on Speed and
      Curvature of Body Movements.
AB  - Improving balance performance among the elderly is of utmost importance because
      of the increasing number of injuries and fatalities caused by fall incidences.
      Digital games controlled by body movements (exergames) have been proposed as a
      way to improve balance among older people. However, the assessment of balance
      performance in real-time during exergaming remains a challenging task. This
      assessment could be used to provide instantaneous feedback and automatically
      adjust the exergame difficulty. Such features could potentially increase the
      motivation of the player, thus augmenting the effectiveness of exergames. As
      clear differences in balance performance have been identified between older and
      younger people, distinguishing between older and younger adults can help
      identifying measures of balance performance. We used generalized linear models to
      investigate whether the assessment of balance performance based on movement speed
      can be improved by incorporating curvature of the movement trajectory into the
      analysis. Indeed, our results indicated that curvature improves the performance
      of the models. Five-fold cross validation indicated that our method is promising
      for the assessment of balance performance in real-time by showing more than 90%
      classification accuracy. Finally, this method could be valuable not only for
      exergaming, but also for real-time assessment of body movements in sports,
      rehabilitation, and medicine.

PMID- 29324409
TI  - Assessment of Spasticity by a Pendulum Test in SCI Patients Who Exercise FES
      Cycling or Receive Only Conventional Therapy.
AB  - Increased muscle tone and exaggerated tendon reflexes characterize most of the
      individuals after a spinal cord injury (SCI). We estimated seven parameters from
      the pendulum test and used them to compare with the Ashworth modified scale of
      spasticity grades in three populations (retrospective study) to assess their
      spasticity. Three ASIA B SCI patients who exercised on a stationary FES bicycle
      formed group F, six ASIA B SCI patients who received only conventional therapy
      were in the group C, and six healthy individuals constituted the group H. The
      parameters from the pendulum test were used to form a single measure, termed the
      PT score, for each subject. The pendulum test parameters show differences between
      the F and C groups, but not between the F and H groups, however, statistical
      significance was limited due to the small study size. Results show a small
      deviation from the mean for all parameters in the F group and substantial
      deviations from the mean for the parameters in the C group. PT scores show
      significant differences between the F and C groups and the C and H groups and no
      differences between the F and C groups. The correlation between the PT score and
      Ashworth score was 0.88.

PMID- 29324410
TI  - Decoding Motor Unit Activity From Forearm Muscles: Perspectives for Myoelectric
      Control.
AB  - We prove the feasibility of decomposing high density surface EMG signals from
      forearm muscles in non-isometric wrist motor tasks of normally limbed and limb
      deficient individuals with the perspective of using the decoded neural
      information for prosthesis control. For this purpose, we recorded surface EMG
      signals during motions of three degrees of freedom of the wrist in seven normally
      limbed subjects and two patients with limb deficiency. The signals were
      decomposed into individual motor unit activity with a convolutive blind source
      separation algorithm. On average, for each subject, 16 +/- 7 motor units were
      identified per motor task. The discharge timings of these motor units were
      estimated with an accuracy > 85%. Moreover, the activity of 6 +/- 5 motor units
      per motor task was consistently detected in all repetitions of the same task. The
      joint angle at which motor units were first identified was 62.5 +/- 26.4% of the
      range of motion, indicating a prevalence in the identification of high threshold
      motor units. These findings prove the feasibility of accurate identification of
      the neural drive to muscles in contractions relevant for myoelectric control,
      allowing the development of a new generation of myocontrol methods based on motor
      unit spike trains.

PMID- 29324411
TI  - Virtual Activities of Daily Living for Recovery of Upper Extremity Motor
      Function.
AB  - A study was conducted to investigate the effectiveness of virtual activities of
      daily living (ADL) practice using the SaeboVR software system for the recovery of
      upper extremity (UE) motor function following stroke. The system employs Kinect
      sensor-based tracking to translate human UE motion into the anatomical pose of
      the arm of the patient's avatar within a virtual environment, creating a virtual
      presence within a simulated task space. Patients gain mastery of 12 different
      integrated activities while traversing a metaphorical "road to recovery" that
      includes thematically linked levels and therapist-selected difficulty settings.
      Clinical trials were conducted under the study named Virtual Occupational Therapy
      Application. A total of 15 chronic phase stroke survivors completed a protocol
      involving three sessions per week over eight weeks, during which they engaged in
      repetitive task practice through performance of the virtual ADLs. Results show a
      clinically important improvement and statistically significant difference in Fugl
      Meyer UE assessment scores in the study population of chronic stroke survivors
      over the eight-week interventional period compared with a non-interventional
      control period of equivalent duration. Statistically significant and clinically
      important improvements are also found in the wolf motor function test scores.
      These results provide new evidence for the use of virtual ADL practice as a tool
      for UE therapy for stroke patients. Limitations of the study include non-blinded
      assessments and the possibility of selection and/or attrition bias.

PMID- 29324412
TI  - Implicit Negative Sub-Categorization and Sink Diversion for Object Detection.
AB  - In this paper, we focus on improving the proposal classification stage in the
      object detection task and present implicit negative sub-categorization and sink
      diversion to lift the performance by strengthening loss function in this stage.
      First, based on the observation that the "background" class is generally very
      diverse and thus challenging to be handled as a single indiscriminative class in
      existing state-of-the-art methods, we propose to divide the background category
      into multiple implicit sub-categories to explicitly differentiate diverse
      patterns within it. Second, since the ground truth class inevitably has low-value
      probability scores for certain images, we propose to add a "sink" class and
      divert the probabilities of wrong classes to this class when necessary, such that
      the ground truth label will still have a higher probability than other wrong
      classes even though it has low probability output. Additionally, we propose to
      use dilated convolution, which is widely used in the semantic segmentation task,
      for efficient and valuable context information extraction. Extensive experiments
      on PASCAL VOC 2007 and 2012 data sets show that our proposed methods based on
      faster R-CNN implementation can achieve state-of-the-art mAPs, i.e., 84.1%,
      82.6%, respectively, and obtain 2.5% improvement on ILSVRC DET compared with that
      of ResNet.

PMID- 29324413
TI  - Skeleton-Based Human Action Recognition With Global Context-Aware Attention LSTM
      Networks.
AB  - Human action recognition in 3D skeleton sequences has attracted a lot of research
      attention. Recently, long short-term memory (LSTM) networks have shown promising
      performance in this task due to their strengths in modeling the dependencies and
      dynamics in sequential data. As not all skeletal joints are informative for
      action recognition, and the irrelevant joints often bring noise which can degrade
      the performance, we need to pay more attention to the informative ones. However,
      the original LSTM network does not have explicit attention ability. In this
      paper, we propose a new class of LSTM network, global context-aware attention
      LSTM, for skeleton-based action recognition, which is capable of selectively
      focusing on the informative joints in each frame by using a global context memory
      cell. To further improve the attention capability, we also introduce a recurrent
      attention mechanism, with which the attention performance of our network can be
      enhanced progressively. Besides, a two-stream framework, which leverages coarse
      grained attention and fine-grained attention, is also introduced. The proposed
      method achieves state-of-the-art performance on five challenging datasets for
      skeleton-based action recognition.

PMID- 29324414
TI  - No Reference Quality Assessment for Screen Content Images With Both Local and
      Global Feature Representation.
AB  - In this paper, we propose a novel no reference quality assessment method by
      incorporating statistical luminance and texture features (NRLT) for screen
      content images (SCIs) with both local and global feature representation. The
      proposed method is designed inspired by the perceptual property of the human
      visual system (HVS) that the HVS is sensitive to luminance change and texture
      information for image perception. In the proposed method, we first calculate the
      luminance map through the local normalization, which is further used to extract
      the statistical luminance features in global scope. Second, inspired by existing
      studies from neuroscience that high-order derivatives can capture image texture,
      we adopt four filters with different directions to compute gradient maps from the
      luminance map. These gradient maps are then used to extract the second-order
      derivatives by local binary pattern. We further extract the texture feature by
      the histogram of high-order derivatives in global scope. Finally, support vector
      regression is applied to train the mapping function from quality-aware features
      to subjective ratings. Experimental results on the public large-scale SCI
      database show that the proposed NRLT can achieve better performance in predicting
      the visual quality of SCIs than relevant existing methods, even including some
      full reference visual quality assessment methods.

PMID- 29324415
TI  - Convolutional Sparse Coding for RGB+NIR Imaging.
AB  - Emerging sensor designs increasingly rely on novel color filter arrays (CFAs) to
      sample the incident spectrum in unconventional ways. In particular, capturing a
      near-infrared (NIR) channel along with conventional RGB color is an exciting new
      imaging modality. RGB+NIR sensing has broad applications in computational
      photography, such as low-light denoising, it has applications in computer vision,
      such as facial recognition and tracking, and it paves the way toward low-cost
      single-sensor RGB and depth imaging using structured illumination. However, cost
      effective commercial CFAs suffer from severe spectral cross talk. This cross talk
      represents a major challenge in high-quality RGB+NIR imaging, rendering existing
      spatially multiplexed sensor designs impractical. In this work, we introduce a
      new approach to RGB+NIR image reconstruction using learned convolutional sparse
      priors. We demonstrate high-quality color and NIR imaging for challenging scenes,
      even including high-frequency structured NIR illumination. The effectiveness of
      the proposed method is validated on a large data set of experimental captures,
      and simulated benchmark results which demonstrate that this work achieves
      unprecedented reconstruction quality.

PMID- 29324416
TI  - Unsupervised Deep Hashing With Pseudo Labels for Scalable Image Retrieval.
AB  - In order to achieve efficient similarity searching, hash functions are designed
      to encode images into low-dimensional binary codes with the constraint that
      similar features will have a short distance in the projected Hamming space.
      Recently, deep learning-based methods have become more popular, and outperform
      traditional non-deep methods. However, without label information, most state-of
      the-art unsupervised deep hashing (DH) algorithms suffer from severe performance
      degradation for unsupervised scenarios. One of the main reasons is that the ad
      hoc encoding process cannot properly capture the visual feature distribution. In
      this paper, we propose a novel unsupervised framework that has two main
      contributions: 1) we convert the unsupervised DH model into supervised by
      discovering pseudo labels; 2) the framework unifies likelihood maximization,
      mutual information maximization, and quantization error minimization so that the
      pseudo labels can maximumly preserve the distribution of visual features.
      Extensive experiments on three popular data sets demonstrate the advantages of
      the proposed method, which leads to significant performance improvement over the
      state-of-the-art unsupervised hashing algorithms.

PMID- 29324417
TI  - Robust Object Co-Segmentation Using Background Prior.
AB  - Given a set of images that contain objects from a common category, object co
      segmentation aims at automatically discovering and segmenting such common objects
      from each image. During the past few years, object co-segmentation has received
      great attention in the computer vision community. However, the existing
      approaches are usually designed with misleading assumptions, unscalable priors,
      or subjective computational models, which do not have sufficient robustness for
      dealing with complex and unconstrained real-world image contents. This paper
      proposes a novel two-stage co-segmentation framework, mainly for addressing the
      robustness issue. In the proposed framework, we first introduce the concept of
      union background and use it to improve the robustness for suppressing the image
      backgrounds contained by the given image groups. Then, we also weaken the
      requirement for the strong prior knowledge by using the background prior instead.
      This can improve the robustness when scaling up for the unconstrained image
      contents. Based on the weak background prior, we propose a novel MR-SGS model,
      i.e., manifold ranking with the self-learned graph structure, which can infer
      suitable graph structures in a data-driven manner rather than building the fixed
      graph structure relying on the subjective design. Such capacity is critical for
      further improving the robustness in inferring the foreground/background
      probability of each image pixel. Comprehensive experiments and comparisons with
      other state-of-the-art approaches can demonstrate the effectiveness of the
      proposed work.

PMID- 29324418
TI  - NIQSV+: A No-Reference Synthesized View Quality Assessment Metric.
AB  - Benefiting from multi-view video plus depth and depth-image-based-rendering
      technologies, only limited views of a real 3-D scene need to be captured,
      compressed, and transmitted. However, the quality assessment of synthesized views
      is very challenging, since some new types of distortions, which are inherently
      different from the texture coding errors, are inevitably produced by view
      synthesis and depth map compression, and the corresponding original views
      (reference views) are usually not available. Thus the full-reference quality
      metrics cannot be used for synthesized views. In this paper, we propose a novel
      no-reference image quality assessment method for 3-D synthesized views (called
      NIQSV+). This blind metric can evaluate the quality of synthesized views by
      measuring the typical synthesis distortions: blurry regions, black holes, and
      stretching, with access to neither the reference image nor the depth map. To
      evaluate the performance of the proposed method, we compare it with four full
      reference 3-D (synthesized view dedicated) metrics, five full-reference 2-D
      metrics, and three no-reference 2-D metrics. In terms of their correlations with
      subjective scores, our experimental results show that the proposed no-reference
      metric approaches the best of the state-of-the-art full reference and no
      reference 3-D metrics; and outperforms the widely used no-reference and full
      reference 2-D metrics significantly. In terms of its approximation of human
      ranking, the proposed metric achieves the best performance in the experimental
      test.

PMID- 29324419
TI  - Visual Saliency Detection Using Spatiotemporal Decomposition.
AB  - We propose a novel technique for detection of visual saliency in dynamic video
      based on video decomposition. The decomposition obtains the sparse features in a
      particular orientation by exploiting the spatiotemporal discontinuities present
      in a video cube. A weighted sum of the sparse features along three orthogonal
      directions determines the salient regions in the video cubes. The weights
      computed using the frame correlation along three directions are based on the
      characteristic of human visual system that identifies the sparsest feature as the
      most salient feature in a video. Unlike the existing methods, which detect the
      salient region as blob, the proposed approach detects the exact boundaries of
      salient region with minimum false detection. The experimental results confirm
      that the detected salient regions of a video closely resemble the salient regions
      detected by actual tracking of human eyes. The algorithm is tested on different
      types of video contents and compared with the several state-of-the-art methods to
      establish the effectiveness of the proposed method.

PMID- 29324420
TI  - Evaluation of Hierarchical Watersheds.
AB  - This paper aims to understand the practical features of hierarchies of
      morphological segmentations, namely the quasi-flat zones hierarchy and watershed
      hierarchies, and to evaluate their potential in the context of natural image
      analysis. We propose a novel evaluation framework for the hierarchies of
      partitions designed to capture various aspects of those representations:
      precision of their regions and contours, possibility to extract high quality
      horizontal cuts and optimal non-horizontal cuts for image segmentation, and the
      ease of finding a set of regions representing a semantic object. This framework
      is used to assess and to optimize hierarchies with respect to the possible pre-
      and post-processing steps. We show that, used in conjunction with a state-of-the
      art contour detector, watershed hierarchies are competitive with the complex
      state-of-the-art methods for hierarchy construction. In particular, the proposed
      framework allows us to identify a watershed hierarchy based on a novel extinction
      value, the number of parent nodes that outperforms the other hierarchies of
      morphological segmentations. This coupled with the fact that watershed
      hierarchies satisfy clear global optimality properties and can be efficiently
      computed on large data, make them valuable candidates for various computer vision
      tasks.

PMID- 29324421
TI  - Analysis on the Effect of Sensor Views in Image Reconstruction Produced by
      Optical Tomography System Using Charge-Coupled Device.
AB  - Optical tomography (OPT) is a method to capture a cross-sectional image based on
      the data obtained by sensors, distributed around the periphery of the analyzed
      system. This system is based on the measurement of the final light attenuation or
      absorption of radiation after crossing the measured objects. The number of sensor
      views will affect the results of image reconstruction, where the high number of
      sensor views per projection will give a high image quality. This research
      presents an application of charge-coupled device linear sensor and laser diode in
      an OPT system. Experiments in detecting solid and transparent objects in crystal
      clear water were conducted. Two numbers of sensors views, 160 and 320 views are
      evaluated in this research in reconstructing the images. The image reconstruction
      algorithms used were filtered images of linear back projection algorithms.
      Analysis on comparing the simulation and experiments image results shows that,
      with 320 image views giving less area error than 160 views. This suggests that
      high image view resulted in the high resolution of image reconstruction.

PMID- 29324422
TI  - Assimilation of Biophysical Neuronal Dynamics in Neuromorphic VLSI.
AB  - Representing the biophysics of neuronal dynamics and behavior offers a principled
      analysis-by-synthesis approach toward understanding mechanisms of nervous system
      functions. We report on a set of procedures assimilating and emulating
      neurobiological data on a neuromorphic very large scale integrated (VLSI)
      circuit. The analog VLSI chip, NeuroDyn, features 384 digitally programmable
      parameters specifying for 4 generalized Hodgkin-Huxley neurons coupled through 12
      conductance-based chemical synapses. The parameters also describe reversal
      potentials, maximal conductances, and spline regressed kinetic functions for ion
      channel gating variables. In one set of experiments, we assimilated membrane
      potential recorded from one of the neurons on the chip to the model structure
      upon which NeuroDyn was designed using the known current input sequence. We
      arrived at the programmed parameters except for model errors due to analog
      imperfections in the chip fabrication. In a related set of experiments, we
      replicated songbird individual neuron dynamics on NeuroDyn by estimating and
      configuring parameters extracted using data assimilation from intracellular
      neural recordings. Faithful emulation of detailed biophysical neural dynamics
      will enable the use of NeuroDyn as a tool to probe electrical and molecular
      properties of functional neural circuits. Neuroscience applications include
      studying the relationship between molecular properties of neurons and the
      emergence of different spike patterns or different brain behaviors. Clinical
      applications include studying and predicting effects of neuromodulators or
      neurodegenerative diseases on ion channel kinetics.

PMID- 29324423
TI  - Effects of Omega-3 Fatty Acids Against Chemotherapy-induced Mucositis: A Double
      blind Randomized Clinical Trial.
AB  - OBJECTIVE: This double-blind randomized clinical trial evaluates the ef cacy and
      route of administration of omega-3 fatty acids for the prevention and treatment
      of oral mucositis in patients undergoing che- motherapy in Iranian hospitals.
      MATERIALS AND METHODS: Sixty patients developing World Health Organization (WHO)
      grade 1 oral mucositis were randomized to the omega-3 fatty acid (n=30) or
      placebo (n=30) group. Mucositis was assessed according to the WHO, Western
      Consortium for Cancer Nursing Research, and Oral Mucositis Weekly Questionnaire
      cri- teria at baseline and rst, second, and third weeks of chemotherapy un- til
      mucositis resolved. RESULTS: Differences in the severity of mucositis between the
      omega-3 and placebo groups in the rst, second, and third weeks of treatment based
      on the WHO criteria were noted. This study showed that patients in the omega-3
      group experienced less pain during the rst, second, and third weeks of treatment.
      CONCLUSIONS: Omega-3 fatty acids are a safe, effective method for preventing and
      treating oral mucositis in patients receiving mucotoxic cancer chemotherapy.

PMID- 29324424
TI  - Larval Therapy for Chronic Cutaneous Ulcers: Historical Review and Future
      Perspectives.
AB  - Cutaneous ulcers tend to become chronic and have a profound impact on quality of
      life. These wounds may become infected and lead to greater morbidity and even
      mortality. In the past, larvae (ie, maggots) of certain common flies (Lucilia
      sericata and Lucilia cuprina) were considered useful in ulcer management because
      they only remove necrotic tissue while promoting healthy tissue in the wound bed,
      thus helping wounds heal faster. Recently, maggots from several other fly species
      (Calliphora vicina, Calliphora vomitoria, Phormia regina, Chrysomya albiceps,
      Sarcophaga carnaria, and Hermetia illucens) have been shown in vitro to possess
      characteristics (ie, debridement efficacy and putative antimicrobial
      potentialities) that make them suitable candidates for possible use in clinical
      practice. This review presents a historical analysis of larval debridement and
      speculates future directions based on the literature presented.

PMID- 29324425
TI  - Comparison of a Saline-coupled Bipolar Sealer Versus Traditional Electrosurgery
      in a Porcine Model of Chronic Wound Healing.
AB  - OBJECTIVE: This study examines the healing dynamics of in vivo porcine muscle
      tissue wounds hemostatically treated with a saline-coupled bipolar tissue sealer
      (SCBS) compared with traditional electrosurgical (ES) coagulation. MATERIALS AND
      METHODS: Six cutaneous incisions were created on the dorsum of 28 adult male
      Yorkshire swine. The underlying muscle tissue was incised with a cold scalpel
      then treated with either SCBS (at 170 W) or traditional ES (at Coag 45 W). Time
      to hemostasis was recorded. Animals were humanely euthanized at day 2 and weeks
      2, 3, or 8; treated tissue was harvested for histopathological evaluation.
      RESULTS: After 8 weeks, the extent of wound healing was similar between SCBS and
      ES. Both devices controlled bleeding effectively; however, SCBS-treated wounds
      exhibited a greater depth of thermal effect over the first 3 weeks despite a
      shorter treatment time. Wounds treated with SCBS demonstrated fewer inflammatory
      markers at early time points but healed more slowly, with scores that lagged
      behind ES for collagen deposition, fibrous tissue maturity, extracellular matrix,
      and stage of healing. Myofiber regeneration notably increased in SCBS-treated
      wounds at weeks 2, 3, and 8. By the end of the 8-week recovery period, there were
      no significant differences in healing parameters between the 2 groups.
      CONCLUSIONS: Overall, both devices elicited similar progression of healing by 8
      weeks. The SCBS produced a deeper thermal effect in a shorter treatment time and
      improved myofiber regeneration compared with ES and had an equivalent overall
      course of healing.

PMID- 29324426
TI  - A Sweet Solution: The Use of Medical-grade Honey on Oral Mucositis in the
      Pediatric Oncology Patient.
AB  - INTRODUCTION: Pediatric patients develop mucositis when receiving treatments such
      as chemotherapy and radiation; the most common and sensitive is oral mucositis.
      Mouth rinses containing antimicrobial, antihistamine, and analgesic medications
      are the mainstay for pediatric patients; however, patients often refuse these
      rinses due to the taste or texture. Also, patients under 1 year of age are unable
      to use these products. OBJECTIVE: Herein, the improvement of oral mucositis with
      standard oral care and additional use of active Leptospermum honey in pediatric
      oncology patients after chemotherapy is demonstrated. MATERIALS AND METHODS:
      Patients received oral care every 4 hours followed by application of the honey
      paste 3 times daily. The honey paste was applied with a sponge swab to coat the
      mouth. Patients either swished and spit or had excess honey suctioned out. At
      completion of this evaluation, the honey treatment was used in 10 pediatric
      oncology patients between the ages of 9 months and 17 years. RESULTS: The
      Leptospermum honey paste was easy to apply and was well received by all patients.
      Healing was observed within 3 days, and patients in all cases reported decreases
      in pain. Decreased wounds and bleeding were evident in all cases within 5 days.
      CONCLUSIONS: Leptospermum honey paste proved to be effective in all participating
      patients.

PMID- 29324427
TI  - Lemons in the Arizona Sunshine: The Effects of Furocoumarins Leading to
      Phytophotodermatitis and Burn-like Injuries.
AB  - INTRODUCTION: Phytophototoxic dermatitis is a strong phototoxic reaction to
      ultraviolet A (UV-A) radiation exposure after cutaneous contact with citrus fruit
      containing furocoumarins, leading to skin injury. At the Arizona Burn Center
      (Phoenix, AZ), the majority of these injuries are managed in the outpatient
      setting. CASE REPORT: The authors present a pediatric admission for burn-like
      injuries following prolonged cutaneous exposure to lemons while playing in the
      Arizona sunshine. A 7-year-old girl playing in her backyard squeezed lemon juice
      onto her skin while in the hot Arizona sunshine; within 24 hours, the child
      experienced pain, erythema, and blistering to multiple areas of her skin. She was
      admitted to the authors' burn center for wound care and pain control. She had
      scattered first-degree and second-degree burn-like lesions to her face, neck, and
      chest as well as bilateral forearms, hands, lower extremities, and feet. After
      blister debridement, appropriate dressing care, and pain medication, the patient
      was discharged home after 4 days of hospitalization with appropriate clinical
      follow-up. CONCLUSIONS: Burn-like lesions caused by furocoumarins after cutaneous
      absorption and UV-A exposure are known clinical entities in Arizona. The
      sequential progression from erythema to blisters equivalent to second-degree burn
      like lesions to cutaneous hyperpigmentation is a well-described clinical triad.
      Meticulous wound care and pain control for the treatment of these burn-like
      lesions are essential as is the need for the wound care specialist to be well
      versed on this topic to quickly identify the etiology of the injury, thereby
      avoiding misdiagnosing the patient with nonaccidental traumatic injuries.

PMID- 29324428
TI  - Malignant Transformation of a Site of Prior Diabetic Foot Ulceration to Verrucous
      Carcinoma: A Case Report.
AB  - The case of a 62-year-old Caucasian man with type 1 diabetes who developed
      malignant transformation of an area of prior diabetic foot ulceration (DFU) is
      reported. He had significant hallux valgus deformity, multiple episodes of
      healing and breakdown, and eventual transformation to verrucous carcinoma (VC).
      This case report highlights the malignant transformation of a site of previous
      DFU to VC, which, to the best of the authors' knowledge, has not yet been
      described in the literature. There has been little research performed that
      examines VC in the diabetic population. This case report also highlights the
      importance of clinical suspicion for malignant transformation as well as the use
      of subsequent biopsy when necessary.

PMID- 29324429
TI  - A Pilot Clinical Study of a Safe and Efficient Stool Management System in
      Patients With Fecal Incontinence.
AB  - INTRODUCTION: According to the Wound Ostomy Continence Nursing Society's
      Continence Committee, the incidence of fecal incontinence (FI) can occur from 18%
      to 37% in an acute care setting. A stool management system has been designed to
      manage FI in bedridden patients and has proven to be efficacious in wound
      management and prevention and infection control, provide safer patient outcomes,
      and enhance ease of nursing. OBJECTIVE: This study aims to evaluate the safety
      and efficacy of an intrarectal device intended to manage fecal incontinence in
      hospitalized bedridden patients through nonclinical and clinical testings.
      MATERIALS AND METHODS: An uncontrolled pilot evaluation in 20 patients was
      performed as part of a value-based purchasing evaluation at a tertiary hospital
      in Tucson, Arizona, to assess safety and efficacy in infection control and wound
      care. The company-provided engineering bench-top studies of insertion and
      withdrawal forces of the device versus existing intrarectal balloon catheters
      also were evaluated. RESULTS: The device has broader patient eligibility and
      potentially allows 3 times more FI patients to be managed safely. It has lower
      intrarectal pressures compared with indwelling balloon catheters. CONCLUSIONS:
      This study, along with pilot clinical findings, suggests that this technology
      minimizes the pressure exerted on the rectal wall. There were significantly fewer
      forces against the anorectal mucosa compared with the cuff-based catheter during
      insertion, withdrawal, and accidental expulsion.

PMID- 29324430
TI  - A Prospective, Multicenter Study to Compare a Disposable, High-fluid Capacity
      Underpad to Nonpermeable, Disposable, Reusable Containment Products on
      Incontinence-associated Dermatitis Rates Among Skilled Nursing Facility
      Residents.
AB  - Due to the high prevalence of incontinence among skilled nursing facility (SNF)
      residents, incontinence-associated derma- titis (IAD) is a common occurrence. In
      addition, facility staff may mistakenly identify IAD as a pressure injury. A
      prospective, descriptive, multicenter study was conducted in 3 Connecticut
      facilities to evaluate the effect of substituting a disposable, high- uid
      capacity underpad for nonpermeable disposable and reusable containment products
      on the rate of IADs. Residents with and without IAD but with high IAD risk scores
      who were bed- or chairbound or ambulatory and used disposable nonpermeable briefs
      and underpads or reusable, laundered containment products when in bed longer than
      2 hours were randomly enrolled and observed for a 4-week period. Facility staff
      were trained on the importance of differentiating between IAD and pressure
      injury; they substituted the study product (a disposable, high- uid capacity
      underpad) for all previously used containment products. Patient risk for IAD and
      skin condition were assessed using the Perineal Assessment Tool (PAT) and the
      Skin Condition Assessment Tool (SAT), respectively, at 5 time points: baseline,
      week 1, week 2, week 3, and week 4. The PAT is a 4-item instrument based
      conceptually on the 4 determinants in perineal skin breakdown; subscales are
      rated from 1 (least risk) to 3 (most risk), with a total score range of 4 to 12.
      The SAT is used to evaluate IAD speci cally, generating a cumulative severity
      score ranging from 0 to 3 on area of skin affected, degree of redness, and depth
      of ero- sion. Final data analysis was conducted on 40 residents: 25 had IAD
      present at enrollment and 15 were deemed high risk for developing IAD. Mean SAT
      scores in the 25 participants with IAD decreased with signi cance at week 1 (P =
      .0016), week 2 (P = .0023), week 3 (P = .0005), and week 4 (P <.0001). Baseline
      IAD severity scores averaged 3.3 +/- 1.7. Overall IAD average severity scores in
      this group decreased from baseline mean of 3.3 +/- 1.7 to 0.7 +/- 1.4 at week 4
      (P <.001). The 15 participants with intact, nondamaged skin at enrollment did not
      develop IAD from baseline to week 4, and PAT score risk levels decreased from
      high (7 or greater) to low (6 or less) as a result of a speci c reduction in the
      duration of irritant exposure category for 11 (73%) of this group of participants
      by week 4. PAT risk level scores for both IAD and non-IAD participants at
      baseline averaged 8.1 +/- 1.4; after 4 weeks, they averaged 7.0 +/- 1.5).
      Although change was not significant, results suggest the use of a disposable,
      high- uid capacity underpad improved SAT scores over time. IAD rates increased in
      each facility, but pressure injury incidence rates decreased for the study
      duration. Replacing a nonpermeable, reusable containment product with a
      disposable, high- uid capacity underpad when SNF residents are in bed longer than
      2 hours may impact the severity of IAD and reduce its incidence. The inverse
      impact reported on IAD and pressure injury incidence rates 1 month after training
      suggest study educational efforts had a short-lasting effect. Future research is
      indicated to determine the most effective method to improve nurses' ability to
      identify and distinguish IAD from pressure injury in the SNF setting.

PMID- 29324431
TI  - A Descriptive, Qualitative Study to Assess Patient Experiences Following Stoma
      Reversal After Rectal Cancer Surgery.
AB  - Standard surgical treatment for patients operated for rectal cancer is
      abdominoperineal excision of the tumor result- ing in a permanent colostomy or an
      anterior resection, often with construction of a temporary loop ileostomy. Both
      options impact bowel function. Living with a permanent colostomy has been studied
      in depth, but knowledge is limited about patients' experiences living with a
      resected rectum after stoma reversal and how it affects daily life. A qualitative
      study was conducted to describe the rst 4 to 6 weeks after reversal of a
      temporary loop ileostomy due to rectal cancer. Patients from 1 university
      hospital and 1 county hospital in Sweden were recruited by telephone and were
      eligible to participate in the study if they: 1) had been operated for rectal
      cancer with an anterior resection and a temporary loop ileostomy that had been
      reversed; 2) were >18 years of age, fully oriented, and understood the Swedish
      language; and 3) had a postoperative course without complications. Interviews
      were conducted be- tween December 2013 and June 2015 either at the hospital or at
      the participants' homes. Participants were asked to narrate their experiences
      since stoma reversal. Probing open-ended questions were used to stimulate
      narration and clarify and enhance understanding. The interviews were recorded,
      transcribed verbatim, and analyzed us- ing thematic content analysis. The 16
      participants included 9 women and 7 men (median age 67 years). Three (3) main
      themes emerged: Life being controlled by the altered bowel function, with the
      subthemes loss of control over bowel function, uncertainty regarding bowel
      function, and being limited in social life; Striving to regain control over the
      bowel, with the subthemes using ability and knowledge, social support, and being
      grateful and hopeful; and A desire to be normal, with subthemes getting rid of
      the stoma and restoration of body image. Patients experienced severe bowel
      function problems, including increased bowel movement frequency and inability to
      anticipate or trust bowel function after stoma reversal. Outwardly, patients
      experienced a signi cant improvement in body image but continued to struggle with
      suboptimal bowel function. Patients needed reassurance that their bowel symptoms
      were normal. Participants strove to regain control over bowel function using
      various strategies, including what they had learned about diet and medication
      before stoma reversal and by trying to defy the restrictions of their new normal.
      They felt they were ghting to regain bowel control without help from health care
      professionals. In order to cope with altered bowel function, they needed the
      support of family and friends. The results suggest that, following stoma
      reversal, patients need information about available treatments to address their
      symptoms and require regular follow- up visits to evaluate and address functional
      results.

PMID- 29324432
TI  - An Overview of Clinical and Health Economic Evidence Regarding Porcine Small
      Intestine Submucosa Extracellular Matrix in the Management of Chronic Wounds and
      Burns.
AB  - Small intestine submucosa (SIS) has been extensively evaluated in preclinical
      models and developed into commercially produced medical technologies intended for
      use in several different indications. The SIS extracellular matrix cellular
      and/or tissue-based product is a commercially available, porcine-derived SIS
      dressing. The purpose of this review was to consider the role of the SIS dressing
      in the management of chronic wounds and burns. Using a variety of search terms
      from the literature to describe the SIS dressing, the following databases were
      searched: PubMed, York Centre for Reviews and Dissemination database, National
      Health Service Economic Evaluation database, Health Technology Assessment
      database, and the Cochrane Library. The search identified 78 studies of which 21
      met the inclusion/exclusion criteria. Of those, 14 involved chronic wounds, 3
      described the management of burn wounds, and 4 were economic evaluations. The
      wide variety of comparative treatments and outcomes studied precluded the use of
      meta-analysis techniques. Study results show SIS dressings may improve outcomes
      in chronic wounds and cost less than several alternative biological wound
      treatments. Studies to examine their efficacy in burn wound management are
      warranted.

PMID- 29324433
TI  - Optoelectronic figure of merit of a metal nanoparticle-quantum dot (MNP-QD)
      hybrid molecule for assessing its suitability for sensing applications.
AB  - Recently, many have studied various configurations of metal nanoparticle-quantum
      dot (MNP-QD) hybrid molecules based on different metals and tunable parameters.
      In this paper, we aim to incite the interest in using MNP-QD nanohybrids, which
      possess sensing capabilities superior to those of the individual constituents,
      for sensing applications that rely on scattered light. When assessing whether a
      given MNP-QD configuration is suited for an application, sometimes it is hard to
      assess the pros and cons of a given configuration against other candidates. Here
      we propose a simple, elegant relative figure of merit (RFoM), which focuses on
      maximizing the scattered intensity and the refractive index sensitivity of the
      nanohybrid, to rank the suitability of viable MNP-QD configurations for a
      particular sensing application. We use the proposed RFoM to analyse the optical
      spectra of noble, transition, post transition and alkali metal based MNP-QD
      nanohybrids using the representative metals Au, Ag, Cu, Al and Na, adopting a
      generalized nonlocal optical response (GNOR) method based cavity QED approach.
      Based on our observations, we suggest how the usage of MNP-QD nanohybrids could
      improve the conventionally studied tumour targeting applications. Moreover, we
      propose potential substitutes for noble metals conventionally considered for MNP
      QD nanohybrids.

PMID- 29324434
TI  - Room temperature synthesis of ReS2 through aqueous perrhenate sulfidation.
AB  - In this study, a direct sulfidation reaction of ammonium perrhenate (NH4ReO4)
      leading to a synthesis of rhenium disulfide (ReS2) is demonstrated. These
      findings reveal the first example of a simplistic bottom-up approach to the
      chemical synthesis of crystalline ReS2. The reaction presented here takes place
      at room temperature, in an ambient and solvent-free environment and without the
      necessity of a catalyst. The atomic composition and structure of the as
      synthesized product were characterized using several analysis techniques
      including energy dispersive x-ray spectroscopy, x-ray photoelectron spectroscopy,
      x-ray diffraction, transmission electron microscopy, Raman spectroscopy,
      thermogravimetric analysis and differential scanning calorimetry. The results
      indicated the formation of a lower symmetry (1T') ReS2 with a low degree of layer
      stacking.

PMID- 29324435
TI  - Intermediate-valence state of the Sm and Eu in SmB6 and EuCu2Si2: neutron
      spectroscopy data and analysis.
AB  - Magnetic neutron scattering data for Sm (SmB6, Sm(Y)S) and Eu (EuCu2Si2-x Ge x )
      intermediate-valence compounds have been analysed in terms of a generalized model
      of the intermediate-radius exciton. Special attention is paid to the correlation
      between the average ion's valence and parameters of the low-energy excitation in
      the neutron spectra, such as the resonance mode, including its magnetic form
      factor. Along with specific features of the formation of the intermediate-valence
      state for Sm and Eu ions, common physical mechanisms have been revealed for
      systems based on these elements from the middle of the rare-earth series. A
      consistent description of the existing experimental data has been obtained by
      using the concept of a loosely bound hole for the Eu f-electron shell in the
      intermediate-valence state, in analogy with the previously established loosely
      bound electron model for the Sm ion.

PMID- 29324436
TI  - Field effect transistors and phototransistors based upon p-type solution
      processed PbS nanowires.
AB  - We demonstrate the fabrication of solution processed highly crystalline p-type
      PbS nanowires via the oriented attachment of nanoparticles. The analysis of
      single nanowire field effect transistor (FET) devices revealed a hole conduction
      behaviour with average mobilities greater than 30 cm2 V-1 s-1, which is an order
      of magnitude higher than that reported to date for p-type PbS colloidal
      nanowires. We have investigated the response of the FETs to near-infrared light
      excitation and show herein that the nanowires exhibited gate-dependent photo
      conductivities, enabling us to tune the device performances. The responsivity was
      found to be greater than 104 A W-1 together with a detectivity of 1013 Jones,
      which benefits from a photogating effect occurring at negative gate voltages.
      These encouraging detection parameters are accompanied by relatively short
      switching times of 15 ms at positive gate voltages, resulting from a combination
      of the standard photoconduction and the high crystallinity of the nanowires.
      Collectively, these results indicate that solution-processed PbS nanowires are
      promising nanomaterials for infrared photodetectors as well as p-type nanowire
      FETs.

PMID- 29324437
TI  - Performance of a high-resolution depth-encoding PET detector module using
      linearly-graded SiPM arrays.
AB  - The goal of this study was to exploit the excellent spatial resolution
      characteristics of a position-sensitive silicon photomultiplier (SiPM) and
      develop a high-resolution depth-of-interaction (DOI) encoding positron emission
      tomography (PET) detector module. The detector consists of a 30  *  30 array of
      0.445  *  0.445  *  20 mm3 polished LYSO crystals coupled to two 15.5  *  15.5
      mm2 linearly-graded SiPM (LG-SiPM) arrays at both ends. The flood histograms show
      that all the crystals in the LYSO array can be resolved. The energy resolution,
      the coincidence timing resolution and the DOI resolution were 21.8  +/-  5.8%,
      1.23  +/-  0.10 ns and 3.8  +/-  1.2 mm, respectively, at a temperature of -10 
      degrees C and a bias voltage of 35.0 V. The performance did not degrade
      significantly for event rates of up to 130 000 counts s-1. This detector
      represents an attractive option for small-bore PET scanner designs that
      simultaneously emphasize high spatial resolution and high detection efficiency,
      important, for example, in preclinical imaging of the rodent brain with
      neuroreceptor ligands.

PMID- 29324438
TI  - An improved ring removal procedure for in-line x-ray phase contrast tomography.
AB  - The suppression of ring artifacts in x-ray computed tomography (CT) is a required
      step in practical applications; it can be addressed by introducing refined
      digital low pass filters within the reconstruction process. However, these
      filters may introduce additional ringing artifacts when simultaneously imaging
      pure phase objects and elements having a non-negligible absorption coefficient.
      Ringing originates at sharp interfaces, due to the truncation of spatial high
      frequencies, and severely affects qualitative and quantitative analysis of the
      reconstructed slices. In this work, we discuss the causes of ringing artifacts,
      and present a general compensation procedure to account for it. The proposed
      procedure has been tested with CT datasets of the mouse central nervous system
      acquired at different synchrotron radiation facilities. The results demonstrate
      that the proposed method compensates for ringing artifacts induced by low pass
      ring removal filters. The effectiveness of the ring suppression filters is not
      altered; the proposed method can thus be considered as a framework to improve the
      ring removal step, regardless of the specific filter adopted or the imaged
      sample.

PMID- 29324440
TI  - Micro-patterned graphene-based sensing skins for human physiological monitoring.
AB  - Ultrathin, flexible, conformal, and skin-like electronic transducers are emerging
      as promising candidates for noninvasive and nonintrusive human health monitoring.
      In this work, a wearable sensing membrane is developed by patterning a graphene
      based solution onto ultrathin medical tape, which can then be attached to the
      skin for monitoring human physiological parameters and physical activity. Here,
      the sensor is validated for monitoring finger bending/movements and for
      recognizing hand motion patterns, thereby demonstrating its future potential for
      evaluating athletic performance, physical therapy, and designing next-generation
      human-machine interfaces. Furthermore, this study also quantifies the sensor's
      ability to monitor eye blinking and radial pulse in real-time, which can find
      broader applications for the healthcare sector. Overall, the printed graphene
      based sensing skin is highly conformable, flexible, lightweight, nonintrusive,
      mechanically robust, and is characterized by high strain sensitivity.

PMID- 29324439
TI  - Hybrid dose calculation: a dose calculation algorithm for microbeam radiation
      therapy.
AB  - Microbeam radiation therapy (MRT) is still a preclinical approach in radiation
      oncology that uses planar micrometre wide beamlets with extremely high peak
      doses, separated by a few hundred micrometre wide low dose regions. Abundant
      preclinical evidence demonstrates that MRT spares normal tissue more effectively
      than conventional radiation therapy, at equivalent tumour control. In order to
      launch first clinical trials, accurate and efficient dose calculation methods are
      an inevitable prerequisite. In this work a hybrid dose calculation approach is
      presented that is based on a combination of Monte Carlo and kernel based dose
      calculation. In various examples the performance of the algorithm is compared to
      purely Monte Carlo and purely kernel based dose calculations. The accuracy of the
      developed algorithm is comparable to conventional pure Monte Carlo calculations.
      In particular for inhomogeneous materials the hybrid dose calculation algorithm
      out-performs purely convolution based dose calculation approaches. It is
      demonstrated that the hybrid algorithm can efficiently calculate even complicated
      pencil beam and cross firing beam geometries. The required calculation times are
      substantially lower than for pure Monte Carlo calculations.

PMID- 29324441
TI  - A study of lateral fall-off (penumbra) optimisation for pencil beam scanning
      (PBS) proton therapy.
AB  - The lateral fall-off is crucial for sparing organs at risk in proton therapy. It
      is therefore of high importance to minimize the penumbra for pencil beam scanning
      (PBS). Three optimisation approaches are investigated: edge-collimated uniformly
      weighted spots (collimation), pencil beam optimisation of uncollimated pencil
      beams (edge-enhancement) and the optimisation of edge collimated pencil beams
      (collimated edge-enhancement). To deliver energies below 70 MeV, these strategies
      are evaluated in combination with the following pre-absorber methods: field
      specific fixed thickness pre-absorption (fixed), range specific, fixed thickness
      pre-absorption (automatic) and range specific, variable thickness pre-absorption
      (variable). All techniques are evaluated by Monte Carlo simulated square fields
      in a water tank. For a typical air gap of 10 cm, without pre-absorber collimation
      reduces the penumbra only for water equivalent ranges between 4-11 cm by up to
      2.2 mm. The sharpest lateral fall-off is achieved through collimated edge
      enhancement, which lowers the penumbra down to 2.8 mm. When using a pre-absorber,
      the sharpest fall-offs are obtained when combining collimated edge-enhancement
      with a variable pre-absorber. For edge-enhancement and large air gaps, it is
      crucial to minimize the amount of material in the beam. For small air gaps
      however, the superior phase space of higher energetic beams can be employed when
      more material is used. In conclusion, collimated edge-enhancement combined with
      the variable pre-absorber is the recommended setting to minimize the lateral
      penumbra for PBS. Without collimator, it would be favourable to use a variable
      pre-absorber for large air gaps and an automatic pre-absorber for small air gaps.

PMID- 29324444
TI  - Erratum.

PMID- 29324442
TI  - The epithelial-to-mesenchymal transition activator ZEB1 initiates a prometastatic
      competing endogenous RNA network.
AB  - Epithelial tumor cells undergo epithelial-to-mesenchymal transition (EMT) to gain
      metastatic activity. Competing endogenous RNAs (ceRNAs) have binding sites for a
      common set of microRNAs (miRs) and regulate each other's expression by sponging
      miRs. Here, we address whether ceRNAs govern metastasis driven by the EMT
      activating transcription factor ZEB1. High miR-181b levels were correlated with
      an improved prognosis in human lung adenocarcinomas, and metastatic tumor cell
      lines derived from a murine lung adenocarcinoma model in which metastasis is ZEB1
      driven were enriched in miR-181b targets. ZEB1 relieved a strong basal repression
      of alpha1 integrin (ITGA1) mRNA, which in turn upregulated adenylyl cyclase 9
      mRNA (ADCY9) by sponging miR181b. Ectopic expression of the ITGA1 3'-untranslated
      region reversed miR-181b-mediated metastasis suppression and increased the levels
      of adenylyl cyclase 9 protein (AC9), which promoted tumor cell migration and
      metastasis. In human lung adenocarcinomas, ITGA1 and ADCY9 levels were positively
      correlated, and an AC9-activated transcriptomic signature had poor-prognostic
      value. Thus, ZEB1 initiates a miR-181b-regulated ceRNA network to drive
      metastasis.

PMID- 29324445
TI  - Contents Vol. 46, 2017.

PMID- 29324443
TI  - Epithelial-mesenchymal transition leads to NK cell-mediated metastasis-specific
      immunosurveillance in lung cancer.
AB  - During epithelial-mesenchymal transition (EMT) epithelial cancer cells
      transdifferentiate into highly motile, invasive, mesenchymal-like cells, giving
      rise to disseminating tumor cells. Few of these disseminated cells successfully
      metastasize. Immune cells and inflammation in the tumor microenvironment were
      shown to drive EMT, but few studies investigated the consequences of EMT for
      tumor immunosurveillance. In addition to initiating metastasis, we demonstrate
      that EMT confers increased susceptibility to natural killer (NK) cells and
      contributes, in part, to the inefficiency of the metastatic process. Depletion of
      NK cells allowed spontaneous metastasis without affecting primary tumor growth.
      EMT-induced modulation of E-cadherin and cell adhesion molecule 1 (CADM1)
      mediated increased susceptibility to NK cytotoxicity. Higher CADM1 expression
      correlates with improved patient survival in 2 lung and 1 breast adenocarcinoma
      patient cohorts and decreased metastasis. Our observations reveal a novel NK
      mediated, metastasis-specific immunosurveillance in lung cancer and present a
      window of opportunity for preventing metastasis by boosting NK cell activity.

PMID- 29324446
TI  - Contents Vol. 46, 2017.

PMID- 29324447
TI  - Characteristic Motor and Nonmotor Symptoms Related to Quality of Life in Drug
      Naive Patients with Late-Onset Parkinson Disease.
AB  - BACKGROUND/AIMS: Unlike young-onset Parkinson disease (YOPD), characteristics of
      late-onset PD (LOPD) have not yet been clearly elucidated. We investigated
      characteristic features and symptoms related to quality of life (QoL) in LOPD
      patients. METHODS: We recruited drug-naive, early PD patients. The patient cohort
      was divided into 3 subgroups based on patient age at onset (AAO): the YOPD group
      (AAO <50 years), the middle-onset PD (MOPD) group, and the LOPD group (AAO >=70
      years). Using various scales for motor symptoms (MS) and non-MS (NMS) and QoL, we
      compared the clinical features and impact on QoL. RESULTS: Of the 132 enrolled
      patients, 26 were in the YOPD group, 74 in the MOPD group, and 32 in the LOPD
      group. Among parkinsonian symptoms, patients in the LOPD group had a lower score
      on the Korean version of the Montreal Cognitive Assessment than the other groups.
      Logistic regression analysis showed genitourinary symptoms were related to the
      LOPD group. Linear regression analysis showed both MS and NMS were correlated
      with QoL in the MOPD group, but only NMS were correlated with QoL in the LOPD
      group. Particularly, anxiety and fatigue affected QoL in the LOPD group.
      CONCLUSION: LOPD patients showed different characteristic clinical features, and
      different symptoms were related with QoL for LOPD than YOPD and MOPD patients.

PMID- 29324448
TI  - The Expression of HSD17B12 Is Associated with COX-2 Expression and Is Increased
      in High-Grade Epithelial Ovarian Cancer.
AB  - OBJECTIVE: The aim of this study was to characterize the expression of
      hydroxysteroid (17beta) dehydrogenase type 12 (HSD17B12), an enzyme involved in
      the synthesis of arachidonic acid (AA), in ovarian cancer, and to study its
      coexpression with its upstream and downstream enzymes in the AA pathway, namely
      elongation of very long chain fatty acids protein 5 (ELOVL5) and cyclooxygenase-2
      (COX-2), respectively. MATERIALS AND METHODS: Samples from benign and malignant
      ovarian neoplastic lesions were immunohistochemically stained with HSD17B12,
      ELOVL5, and COX-2. The staining intensities were quantified with the QuantCenter
      program, and the results were confirmed with visual inspection. Statistical
      significances were calculated with the Student t test, the Mann-Whitney test,
      linear regression, or ANOVA. RESULTS: The expression of the HSD17B12, ELOVL5, and
      COX-2 enzymes increased according to the grade of the endometrioid ovarian
      adenocarcinomas. In contrast, in serous adenocarcinomas, staining with ELOVL5 was
      constantly weak, whereas the expression of HSD17B12 and COX-2 increased with the
      grade or FIGO stage of the cancer, respectively. CONCLUSIONS: The expression of
      HSD17B12 increased along with the severity of ovarian cancer, and the expression
      mimicked COX-2 expression and intensity. This further suggests the involvement of
      HSD17B12 in AA production, and its coexpression with COX-2 indicates a role for
      the enzyme in the increased prostaglandin production during ovarian cancer
      progression.

PMID- 29324449
TI  - Toward Optimizing Vestibular Evoked Myogenic Potentials: Normalization Reduces
      the Need for Strong Neck Muscle Contraction.
AB  - BACKGROUND: The cervical vestibular evoked myogenic potential (cVEMP) represents
      an inhibitory reflex of the saccule measured in the ipsilateral
      sternocleidomastoid muscle (SCM) in response to acoustic or vibrational
      stimulation. Since the cVEMP is a modulation of SCM electromyographic (EMG)
      activity, cVEMP amplitude is proportional to muscle EMG amplitude. We sought to
      evaluate muscle contraction influences on cVEMP peak-to-peak amplitudes (VEMPpp),
      normalized cVEMP amplitudes (VEMPn), and inhibition depth (VEMPid). METHODS:
      cVEMPs at 500 Hz were measured in 25 healthy subjects for 3 SCM EMG contraction
      ranges: 45-65, 65-105, and 105-500 MUV root mean square (r.m.s.). For each range,
      we measured cVEMP sound level functions (93-123 dB peSPL) and sound off, meaning
      that muscle contraction was measured without acoustic stimulation. The effect of
      muscle contraction amplitude on VEMPpp, VEMPn, and VEMPid and the ability to
      distinguish cVEMP presence/absence were evaluated. RESULTS: VEMPpp amplitudes
      were significantly greater at higher muscle contractions. In contrast, VEMPn and
      VEMPid showed no significant effect of muscle contraction. Cohen's d indicated
      that for all 3 cVEMP metrics contraction amplitude variations produced little
      change in the ability to distinguish cVEMP presence/absence. VEMPid more clearly
      indicated saccular output because when no acoustic stimulus was presented the
      saccular inhibition estimated by VEMPid was zero, unlike those by VEMPpp and
      VEMPn. CONCLUSION: Muscle contraction amplitude strongly affects VEMPpp
      amplitude, but contractions 45-300 MUV r.m.s. produce stable VEMPn and VEMPid
      values. Clinically, there may be no need for subjects to exert high contraction
      effort. This is especially beneficial in patients for whom maintaining high SCM
      contraction amplitudes is challenging.

PMID- 29324450
TI  - Quantification of Myosin Heavy Chain Isoform mRNA Transcripts in the
      Supraspinatus Muscle of Vertical Clinger Primates.
AB  - Vertical clinging is a specialized form of locomotion characteristic of the
      primate family Callitrichidae. Vertical clinging requires these pronograde
      primates to maintain a vertical posture, so the protraction of their forelimbs
      must resist gravity. Since pronograde primates usually move as horizontal
      quadrupeds, we hypothesized that the supraspinatus muscle of vertical clingers
      would present specific characteristics related to the functional requirements
      imposed on the shoulder area by vertical clinging. To test this hypothesis, we
      quantified by real-time quantitative polymerase chain reaction the mRNA
      transcripts of myosin heavy chain (MHC) isoforms in the supraspinatus muscle of
      15 species of pronograde primates, including vertical clingers. Our results
      indicate that the supraspinatus of vertical clingers has a specific expression
      pattern of the MHC isoforms, with a low expression of the transcripts of the slow
      MHC-I isoform and a high expression of the transcripts of the fast MHC-II
      isoforms. We conclude that these differences can be related to the particular
      functional characteristics of the shoulder in vertical clingers, but also to
      other anatomical adaptations of these primates, such as their small body size.

PMID- 29324451
TI  - Aromatase Deficiency due to a Homozygous CYP19A1 Mutation in a 46,XX Egyptian
      Patient with Ambiguous Genitalia.
AB  - Aromatase deficiency (AD) is a very rare disorder resulting from mutations in the
      CYP19A1 gene encoding aromatase, a cytochrome P450 enzyme that plays a pivotal
      role in androgen conversion to estrogens. AD is inherited in an autosomal
      recessive trait, and to date only 35 cases have been described in the literature.
      Herein, we depict a new patient reared as a male, who presented at the age of 21
      years with no palpable testis, hypoplastic scrotum, penis-like phallus (3 cm),
      and penoscrotal hypospadias. The patient was born to consanguineous parents, his
      karyotype was 46,XX, and SRY was negative. Pelvic sonar showed a small
      hypoplastic uterus, and no testis could be identified. Serum testosterone was
      within the reference range of females along with high gonadotropins. Pathology of
      gonadal biopsy showed ovarian stroma negative for oocytic follicle consistent
      with streak gonads. All these data were suggestive of AD, which was subsequently
      confirmed by molecular investigation of the CYP19A1 gene. A homozygous splice
      site mutation in the donor splice site of exon 9 was identified, c.1263 + 1G>T.
      This is the first report of such a rare disorder in an Egyptian patient. Our
      results reinforce the importance of considering AD in patients with 46,XX
      disorders of sex development after ruling out congenital adrenal hyperplasia.

PMID- 29324452
TI  - Adjudication of Transient Ischemic Attack and Stroke in the Multi-Ethnic Study of
      Atherosclerosis.
AB  - BACKGROUND: To describe adjudication of transient ischemic attack (TIA) and
      stroke in an observational study. METHODS: We detail the process used to
      adjudicate TIA and stroke in the Multi-Ethnic Study of Atherosclerosis (MESA), a
      large longitudinal cohort study. Two of three vascular neurologists adjudicated
      each event using specific protocols. We examined the initial agreement, effect of
      imaging on diagnosis of TIA versus ischemic stroke, and effect of strict and less
      strict criteria on the number of ischemic stroke subtypes classified as
      undetermined. RESULTS: Of 573 adjudicated events over 13.5 years of follow-up, 95
      (16.5%) had TIA and 269 (47.0%) had stroke: 211 (78.4%) ischemic, 43 (16.0%)
      hemorrhagic, and 15 (5.6%) other. Disagreements occurred on 16% of initial
      adjudication of events. Using results from imaging, the number with TIA decreased
      by 8.6% and with ischemic stroke increased by 4.1%. Using less strict criteria to
      classify ischemic stroke subtypes reduced the number classified as undetermined,
      from 137 to 59, and numbers classified as cardioembolic and small vessel doubled.
      CONCLUSIONS: We hope that this work will motivate and facilitate investigators to
      use MESA data to investigate issues concerning TIA and stroke and will inform
      investigators seeking to adjudicate TIA and stroke in other studies.

PMID- 29324455
TI  - Erratum.

PMID- 29324454
TI  - Using the Capture-Recapture Method to Estimate the Incidence of Amyotrophic
      Lateral Sclerosis in Beijing, China.
AB  - BACKGROUND: To assess the total, gender-related and ageing process-related
      incidence rates of amyotrophic lateral sclerosis (ALS) in Beijing, China.
      Determine whether the decreased male to female ratio among postmenopausal age
      groups. METHODS: We used the 2-source capture-recapture method to estimate the
      incidence of ALS in Beijing. The primary and secondary data sources were from
      diagnostic hospitals and assisted care institutions in the same area from 2010 to
      2015. RESULTS: A total of 562 cases and 283 cases were extracted from 2 data
      sources, and a total of 962 patients diagnosed with ALS within the 6-year period
      were estimated (95% CI 883-1041). The average yearly incidence was 0.77/100,000
      persons (95% CI 0.71-0.83). The female to male ratio was 1.63. The incidence was
      associated with age and peaked in the 55-64 year age group. There was no obvious
      decline in the male:female ratio among postmenopausal age groups. CONCLUSIONS:
      The total incidence of ALS in Beijing is similar to international reports. The
      onset of ALS is not merely the result of ageing.

PMID- 29324453
TI  - Developmental Origins of Health Span and Life Span: A Mini-Review.
AB  - BACKGROUND: A vast body of research has demonstrated that disease susceptibility
      and offspring health can be influenced by perinatal factors, which include both
      paternal and maternal behavior and environment. Offspring disease risk has the
      potential to affect the health span and life span of offspring. KEY FINDINGS:
      Various maternal factors, such as environmental toxicant exposure, diet, stress,
      exercise, age at conception, and longevity have the potential to influence age
      associated diseases such as cardiovascular disease, obesity, diabetes, and cancer
      risk in offspring. Paternal factors such as diet, age at conception, and
      longevity can potentially impact offspring health span and life span-reducing
      traits as well. PRACTICAL IMPLICATIONS: Continued research could go a long way
      toward defining mechanisms of the developmental origins of life span and health
      span, and eventually establishing regimens to avoid negative developmental
      influences and to encourage positive interventions to potentially increase life
      span and improve health span in offspring.

PMID- 29324457
TI  - Successful First Gait of a Child With Hip-Disarticulation Prosthesis.
AB  - An infant boy underwent hip disarticulation for infantile fibrosarcoma
      immediately after birth. His rehabilitation began when he was 4 mos old and
      involved training with his left (residual) leg. He could stand with support at 12
      mos. His initial prosthesis fitting was performed at the age of 13 mos. He could
      stand and walk with support at 15 mos of age and could walk with no additional
      support and go up and down stairs at 2 yrs. A single-axis prosthetic knee joint
      was introduced at the age of 2 yrs 3 mos. His first gait using a hip prosthesis
      was successful, and his prosthesis was replaced at appropriate intervals with no
      major problems. The authors believe that the key to achieving a successful
      prosthetic gait in children is good communication among the medical team, which
      should comprise an orthopedic doctor, rehabilitation doctor, nurse, physical
      therapist, prosthetist/orthotist, and the patient's parents.

PMID- 29324458
TI  - Ultrasound Imaging and Guided Injection for the Lateral and Posterior Hip.
AB  - Ultrasound has emerged as one of the most utilized tools to diagnose
      musculoskeletal disorders and to assist in interventions. Traditionally,
      sonographic examination of the hip joint has been challenging because most of the
      major structures are deeply situated, thus requiring the use of curvilinear
      transducer for better penetrance. The posterior lateral hip is a frequent area
      for musculoskeletal pain and nerve entrapments. Common disorders include greater
      trochanteric pain syndrome, gluteus medius tendinopathy, piriformis syndrome,
      pudendal neuralgia, and proximal hamstring tendinopathy. The present review
      article aims to delineate sonoanatomy of the posterior lateral hip and to
      exemplify several common ultrasound guided procedures at the greater
      trochanteric, gluteal, and ischial tuberosity regions.

PMID- 29324456
TI  - Targeted Knockdown of Bone Morphogenetic Protein Signaling within Neural
      Progenitors Protects the Brain and Improves Motor Function following Postnatal
      Hypoxia-Ischemia.
AB  - Hypoxic-ischemic injury (HI) to the neonatal human brain results in myelin loss
      that, in some children, can manifest as cerebral palsy. Previously, we had found
      that neuronal overexpression of the bone morphogenic protein (BMP) inhibitor
      noggin during development increased oligodendroglia and improved motor function
      in an experimental model of HI utilizing unilateral common carotid artery
      ligation followed by hypoxia. As BMPs are known to negatively regulate
      oligodendroglial fate specification of neural stem cells and alter
      differentiation of committed oligodendroglia, BMP signaling is likely an
      important mechanism leading to myelin loss. Here, we showed that BMP signaling is
      upregulated within oligodendroglia of the neonatal brain. We tested the
      hypothesis that inhibition of BMP signaling specifically within neural progenitor
      cells (NPCs) is sufficient to protect oligodendroglia. We conditionally deleted
      the BMP receptor 2 subtype (BMPR2) in NG2-expressing cells after HI. We found
      that BMPR2 deletion globally protects the brain as assessed by MRI and protects
      motor function as assessed by digital gait analysis, and that conditional
      deletion of BMPR2 maintains oligodendrocyte marker expression by
      immunofluorescence and Western blot and prevents loss of oligodendroglia.
      Finally, BMPR2 deletion after HI results in an increase in noncompacted myelin.
      Thus, our data indicate that inhibition of BMP signaling specifically in NPCs may
      be a tractable strategy to protect the newborn brain from HI.

PMID- 29324459
TI  - Discordance between lipoprotein particle number and cholesterol content: an
      update.
AB  - PURPOSE OF REVIEW: The cholesterol content within atherogenic apolipoprotein-B
      (apoB) containing lipid particles is the center of consensus guidelines and
      clinicians' focus whenever evaluating a patient's risk for atherosclerotic
      cardiovascular disease. The pathobiology of atherosclerosis requires the
      retention of lipoprotein particles within the vascular intima over time followed
      by maladaptive inflammation resulting in plaque formation and rupture in some.
      The cholesterol content is widely variable within each particle creating either
      cholesterol-deplete or cholesterol-enriched particles. This variance in particle
      cholesterol content varies within and between individuals. Discordance analysis
      exploits this difference in cholesterol content of particles to demonstrate the
      differential significance of LDL-cholesterol (LDL-C) and non-HDL-C from measures
      of lipoprotein particle number in terms of assessing atherosclerotic
      cardiovascular disease risks. RECENT FINDINGS: Three studies have added to the
      growing body of literature of discordance analysis. Despite wide variability of
      discordance cutoffs, baseline risk of atherosclerotic disease, and populations
      sampled, the conclusion remains the same: risk of atherosclerotic disease follows
      apoB lipid particle concentration rather than cholesterol content of lipid
      particles. SUMMARY: In addition to traditional lipid fractions, assessments of
      atherogenic particle number should be strongly considered whenever assessing CVD
      risk in nontreated and treated individuals. There is a need for clinical trials
      that focus not only on the reduction in LDL-C but apoB, as well.

PMID- 29324460
TI  - Sex differences in Alzheimer's disease.
AB  - PURPOSE OF REVIEW: Women are more impacted by Alzheimer's disease than men - they
      are at significantly greater risk of developing Alzheimer's disease, and recent
      research shows that they also appear to suffer a greater cognitive deterioration
      than men at the same disease stage. The purpose of this article is to review
      recent studies on examining sex differences in cognitive function in Alzheimer's
      disease. RECENT FINDINGS: We searched electronically for articles, reviews and
      meta-analyses published between 1/2016 and 12/2017 and identified 298 articles on
      sex differences in cognition in Alzheimer's disease. The key themes to emerge
      were sex differences in cognitive function, risk factors, resilience, and
      cognitive reserve. SUMMARY: Evidence is steadily and increasingly accumulating to
      confirm the poorer cognitive outcome for women than men with Alzheimer's disease.
      Although small in size, the effects occur across a broad range of cognitive
      domains including visuospatial, verbal, episodic memory, and semantic memory -
      some of which typically reveal a sex-related processing advantage for healthy
      women. Explanations have been linked to a variety of factors including
      differences in cognitive reserve, resilience, as well as genetics (apolipoprotein
      epsilon4) and functional and structural brain changes. Sex-related differences in
      risk factors, resilience, cognitive reserve, and rates of deterioration have
      implications for clinical practice.

PMID- 29324461
TI  - Efficacy of treatment immune thrombocytopenic purpura in pregnancy with
      corticosteroids and intravenous immunoglobulin: a prospective follow-up of
      suggested practice.
AB  - : The current study is performed to assess a routine for treatment of immune
      thrombocytopenic purpura in pregnancy. A prospective programme for monitoring and
      treatment with intravenous immunoglobulin or cortisone in pregnancies with immune
      thrombocytopenic purpura was suggested to all delivery units in Sweden. Treatment
      should be avoided if platelet counts were more than 20 * 10/l during pregnancy
      with no bleeding complications and with a target of 100 * 10/l at delivery.
      Descriptive statistics and logistic regression analysis were used. Seventy-five
      pregnancies were followed; treatment was given in 29 (39%) of the pregnancies; in
      13 intravenous immunoglobulin, in six cortisone, in nine a combination of both
      immunoglobulin and cortisone and in one platelets was given. The mean platelet
      increase before delivery after immunoglobulin was 46 * 10/l approximately 3 days
      later. At delivery, 34 (45%) of all pregnancies reached target platelet level
      more than 100 * 10/l, whereas five (7%) had platelets less than 50 * 10/l. Mode
      of delivery and blood loss were similar to a reference group. Of the neonates,
      23% had platelets less than 50 * 10/l with a nadir reached on day 2-4; 9%
      required treatment. Women with platelets less than 20 * 10/l in pregnancy or with
      prior neonatal thrombocytopenia were at a, respectively, five-fold and eight-fold
      increased risk of neonatal thrombocytopenia. A routine to avoid treatment when
      platelets are at least 20 * 10/l during pregnancy and to aim for 100 * 10/l at
      delivery seem safe. Severe maternal thrombocytopenia and prior neonatal
      thrombocytopenia were predictors of neonatal thrombocytopenia.

PMID- 29324462
TI  - Spontaneous Rectus Sheath Hematoma Complicating Therapeutic Heparinization.

PMID- 29324463
TI  - Fractures Related to Tenofovir: A Case/Noncase Study in the European
      Pharmacovigilance Database.
AB  - BACKGROUND: There is no clear consensus on the relationship between tenofovir
      (TDF) and fracture risk because the studies published so far present
      contradictory findings. STUDY QUESTION: Our objective was to detect, from the
      European pharmacovigilance database (EudraVigilance), a signal of fracture risk
      during TDF exposure in patients infected with HIV. METHODS: Herein, we analyze
      all the cases of fractures suspected to be related to TDF recorded in
      EudraVigilance between 2001 and November 10, 2016. A case/noncase method was used
      to assess the association between fractures and TDF, calculating proportional
      reporting ratios (PRRs) and their 95% confidence intervals (CIs) as a measure of
      disproportionality. According to the Medical Dictionary for Regulatory Activities
      (MedDRA) terminology, osteoporotic fractures are included in High Level Group
      Term (HLGT) "Fractures" and traumatic fractures in HLGT "Bone and joint
      injuries," so, we selected cases included in both HLGTs. The noncases used as
      controls were all the remaining adverse drug reaction reports recorded in
      EudraVigilance during the same period. RESULTS: There were 68,113 cases of
      fractures in the 4,776,472 reports recorded in EudraVigilance during the study
      period. TDF was involved in 181 cases. The median latency period until the
      appearance of fracture was 995 days. TDF was present as the only suspect drug in
      140 cases. The PRR of TDF and fractures was 1.11 (95% CI, 0.96-1.28).
      Nevertheless, disproportionality was observed for some types of fractures:
      osteoporotic fractures (PRR 17.24; 95% CI, 9.90-30.01), bone fissure (PRR 16.60;
      95% CI, 6.11-45.10), and pathological fracture (PRR 4.40; 95% CI, 2.77-7.00).
      CONCLUSIONS: Our findings do not show a disproportionality for fractures in
      patients treated with TDF, although disproportionality was found for some types
      of fractures, mainly osteoporotic fractures.

PMID- 29324464
TI  - Sacubitril/Valsartan-Associated Small Bowel Ileus.

PMID- 29324465
TI  - Medical Marijuana, Facts and Questions.

PMID- 29324466
TI  - Rivaroxaban Used for Treatment of a Left Ventricular Thrombus in a Patient With
      Nonischemic Cardiomyopathy.

PMID- 29324467
TI  - Topical Salicylic Acid Hypersensitivity.

PMID- 29324468
TI  - Switching antipsychotic treatment to aripiprazole in psychotic patients with
      neuroleptic-induced tardive dyskinesia: a 24-week follow-up study.
AB  - Aripiprazole is a second-generation antipsychotics, acting as a partial dopamine
      D2 receptor agonist. Previous studies on aripiprazole for tardive dyskinesia (TD)
      treatment were limited and inconclusive. This study was aimed to examine the
      effectiveness of aripiprazole in psychotic patients with a pre-existing TD. This
      was an open-label 24-week prospective cohort study conducted in a public mental
      hospital in Northern Taiwan from January 2009 to February 2010. Psychotic
      patients were cross-titrated of prior antipsychotics with aripiprazole, and the
      severity of TD was assessed at baseline and at weeks 2, 4, 8, 12, 16, 20, and 24.
      The primary study outcome was the change of TD severity, assessed by Abnormal
      Involuntary Movement Scale (AIMS) total score. Responder was defined as the
      reduction of AIMS total scores of no less than 50% from baseline to the study
      endpoint (24 weeks). Thirty psychotic patients with neuroleptic-induced TD were
      recruited. The AIMS total scores significantly decreased from baseline to the
      study endpoint (-7.17+/-5.55). The significant decrease of AIMS total scores
      started at week 2 (P<0.0001), and the change remained significant throughout the
      entire study period (P<0.0001). A greater severity of TD (adjusted odds ratio:
      1.35, 95% confidence interval: 1.04-1.76, P=0.03) or a lower severity of
      parkinsonism (adjusted odds ratio: 0.78, 95% confidence interval: 0.61-0.99,
      P=0.04) at baseline was significantly associated with treatment responders. Our
      findings implicated that aripiprazole can be a promising treatment for clinicians
      considering drug switch in psychotic patients with TD. Further large randomized,
      controlled trials are warranted to confirm our findings.

PMID- 29324469
TI  - Parafibromin-deficient (HPT-JT Type, CDC73 Mutated) Parathyroid Tumors
      Demonstrate Distinctive Morphologic Features.
AB  - The gene CDC73 (previously known as HRPT2) encodes the protein parafibromin.
      Biallelic mutation of CDC73 is strongly associated with malignancy in parathyroid
      tumors. Heterozygous germline mutations cause hyperparathyroidism jaw tumor
      syndrome,which is associated with a high life-time risk of parathyroid carcinoma.
      Therefore loss of parafibromin expression by immunohistochemistry may triage
      genetic testing for hyperparathyroidism jaw tumor syndrome and be associated with
      malignant behavior in atypical parathyroid tumors. We share our experience that
      parafibromin-negative parathyroid tumors show distinctive morphology. We searched
      our institutional database for parathyroid tumors demonstrating complete loss of
      nuclear expression of parafibromin with internal positive controls. Forty-three
      parafibromin-negative tumors from 40 (5.1%) of 789 patients undergoing
      immunohistochemistry were identified. Thirty-three (77%) were external
      consultation cases; the estimated incidence in unselected tumors was 0.19%.
      Sixteen (37.2%) fulfilled World Health Organization 2017 criteria for parathyroid
      carcinoma and 63% had serum calcium greater than 3mmol/L. One of 27 (3.7%)
      noninvasive but parafibromin-negative tumors subsequently metastasized.
      Parafibromin-negative patients were younger (mean, 36 vs. 63 y; P<0.001) and had
      larger tumors (mean, 3.04 vs. 0.62 g; P<0.001). Not all patients had full
      testing, but 26 patients had pathogenic CDC73 mutation/deletions confirmed in
      tumor (n=23) and/or germline (n=16). Parafibromin-negative tumors demonstrated
      distinctive morphology including extensive sheet-like rather than acinar growth,
      eosinophilic cytoplasm, nuclear enlargement with distinctive coarse chromatin,
      perinuclear cytoplasmic clearing, a prominent arborizing vasculature, and,
      frequently, a thick capsule. Microcystic change was found in 21 (48.8%). In
      conclusion, there are previously unrecognized morphologic clues to parafibromin
      loss/CDC73 mutation in parathyroid tumors which, given the association with
      malignancy and syndromic disease, are important to recognize.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- 29324470
TI  - Fibroma-like PEComa: A Tuberous Sclerosis Complex-related Lesion.
AB  - Perivascular epithelioid cell tumor (PEComa), mesenchymal tumors morphologically
      characterized by epithelioid cells, coexpress melanocytic and muscle markers.
      Herein, we describe a heretofore-undescribed tuberous sclerosis complex (TSC)
      related neoplasm, morphologically resembling a soft tissue fibroma-like lesion,
      but showing an immunophenotype resembling PEComa. We identified 3 soft tissue
      fibroma-like lesions in individuals with TSC. We also evaluated 6 TSC-related
      periungual fibroma as well as a range of non-TSC fibroma-like lesions (n=19).
      Immunohistochemistry for HMB-45, desmin, smooth muscle actin, TFE3, and S100 was
      performed on the TSC-related fibromas. Periungual fibromas and non-TSC fibroma
      like lesions were also stained for HMB-45. All 3 TSC patients were female,
      ranging in age from 4 to 51 years (mean, 26.7 y). Two tumors were located in
      extremities and 1 on the chest wall. The tumors showed elongated to stellate
      spindle-shape cells, prominent collagenous background, and lacked mitotic
      activity and cytologic atypia. Immunohistochemically, all 3 tumors were positive
      for HMB-45; smooth muscle actin or desmin was positive in both tumors tested.
      TFE3 was negative. All patients were alive with no evidence of disease with
      median follow-up of 55 months (range, 6 to 131 mo). Non-TSC fibroma-like lesions
      and oral and periungual fibromas were negative for HMB-45. Fibroma-like PEComa, a
      newly recognized soft tissue tumor with a strong association with TSC, mimics
      soft tissue fibroma but shows reactivity with melanocytic markers.

PMID- 29324472
TI  - Collagenous Enteritis is Unlikely a Form of Aggressive Celiac Disease Despite
      Sharing HLA-DQ2/DQ8 Genotypes.
AB  - Collagenous enteritis is an uncommon small intestinal injury pattern with unclear
      pathogenesis. While it has been speculated that collagenous enteritis represents
      a form of refractory celiac disease, recent clinical studies suggest a potential
      link to exposure to the antihypertensive medication olmesartan. Here we
      hypothesized that the pathogenesis of collagenous enteritis involves both genetic
      and environmental factors. All subjects with biopsy-proven collagenous enteritis
      diagnosed between 2002 and 2015 were identified from 2 tertiary care medical
      centers. Human leukocyte antigen (HLA)-DQ genotyping was performed by polymerase
      chain reaction on archived tissue. Celiac disease serology, past medical history,
      medications, smoking history, demographics, histology, clinical management, and
      follow-up were recorded. A total of 32 subjects were included. In contrast to
      celiac disease, subjects with collagenous enteritis were mostly elderly (median
      age at diagnosis, 69 y; range, 33 to 84 y). Seventy percent of collagenous
      enteritis subjects harbored celiac disease susceptibility alleles HLA-DQ2/DQ8;
      however, only 1 subject had elevated serum levels of celiac disease-associated
      autoantibodies while on a gluten-containing diet. Furthermore, 56% of subjects
      were taking nonsteroidal anti-inflammatory drugs, 36% proton-pump inhibitors, 28%
      statins, and 32% olmesartan at the time of diagnosis. Discontinuation of
      olmesartan and treatments with steroids and/or gluten-free diet resulted in
      symptomatic and histologic improvement. Neither lymphoma nor collagenous
      enteritis-related death was seen in this cohort. Therefore, while collagenous
      enteritis shares similar HLA genotypes with celiac disease, the difference in
      demographics, the lack of celiac disease-associated autoantibodies, and potential
      link to medications as environmental triggers suggest the 2 entities are likely
      distinct in pathogenesis.

PMID- 29324471
TI  - Sellar Region Atypical Teratoid/Rhabdoid Tumors (ATRT) in Adults Display DNA
      Methylation Profiles of the ATRT-MYC Subgroup.
AB  - Atypical teratoid/rhabdoid tumor (ATRT) is a highly malignant brain tumor
      predominantly encountered in infants. Mutations of the SMARCB1 gene are the
      characteristic genetic lesion. A small group of ATRT stands out clinically,
      because these tumors are located in the sellar region of adults. To investigate
      if sellar region ATRT in adults represents a molecular distinct entity, we
      characterized molecular alterations in 7 sellar region ATRTs in adults as
      compared with 150 pediatric ATRTs and 47 pituitary adenomas using SMARCB1
      sequencing, multiplex ligation-dependent probe amplification and fluorescence in
      situ hybridization as well as DNA methylation profiling. The median age of the 6
      female and 1 male patients was 56 years. On histopathologic examination, all
      tumors were malignant rhabdoid tumors showing loss of SMARCB1/INI1 protein
      expression. Two cases displayed compound heterozygous SMARCB1 point mutations, 3
      cases showed heterozygous SMARCB1 deletions with point mutations of the other
      allele and 1 case a homozygous SMARCB1 deletion; in 1 case, underlying SMARCB1
      alterations could not be identified. On unsupervised hierarchical cluster
      analysis of DNA methylation profiles, sellar region ATRTs did not form a distinct
      group, but clustered with ATRT-MYC, 1 of 3 recently described molecular subgroups
      of ATRT. On analysis of DNA methylation array intensity data, only 1 sellar
      region ATRT showed characteristic features of pediatric ATRT-MYC, that is, major
      copy number losses affecting the SMARCB1 region. In conclusion, these results
      suggest that sellar region ATRTs in adults form a clinically distinct entity with
      a different mutational spectrum, but epigenetic similarities with pediatric ATRTs
      of the ATRT-MYC subgroup.

PMID- 29324473
TI  - Chondromyxoid Fibroma Arising in Craniofacial Sites: A Clinicopathologic Analysis
      of 25 Cases.
AB  - Chondromyxoid fibroma (CMF) is a rare benign tumor, usually arising in the
      metaphysis of long bones in young adults. Occurrence in craniofacial bones
      presents a particular diagnostic challenge given its unusual location and
      resemblance to malignant mimics. We describe the clinicopathologic features of 25
      cases of craniofacial CMF identified between 1999 and 2017. Patients were 14 men
      and 11 women, with median age of 44 years (range, 5 to 83 y). Sites of
      involvement were sphenoid (7), ethmoid (5), maxilla (3), occipital (2), nasal
      septum (2), palatine (2), temporal (2), orbit (1), and undisclosed skull (1).
      Tumor size ranged from 0.8 to 6.0 cm (median, 2.0 cm). Of the 21 tumors with
      available radiology, 15 arose on the bone surface with expansion into adjacent
      sinuses; 6 were intraosseous. Bony erosion/destruction was present in most
      (13/16) cases, and 7/12 showed calcification on imaging. Microscopically, most
      tumors showed a lobulated growth pattern with hypocellular central chondromyxoid
      areas and peripheral hypercellularity, though many samples were fragmented. Tumor
      cells had ovoid to tapered nuclei and abundant palely eosinophilic cytoplasm,
      frequently with stellate cell processes. Mitoses ranged from 0 to 2 per 10 high
      power fields (median count, 0). None showed necrosis. Significant atypia was
      present in 2 cases, 1 of which was a previously radiated recurrence. Bone
      infiltration was present in 6 cases. Thirteen tumors had focal calcification, and
      2 had foci of hyaline cartilage. All tumors were negative for keratin and GFAP
      (0/24), with frequent positivity for SMA (7/7) and occasional staining for EMA
      (5/24) and S-100 (2/24). Most patients underwent piecemeal excision or curettage
      (5/5 positive margins when reported). Follow-up data were available for 15
      patients, and 5 suffered local recurrence. Craniofacial CMF poses diagnostic
      pitfalls including frequent aggressive radiologic features and lack of a specific
      immunophenotype. Tumors may recur, largely due to the difficulty of obtaining
      clear surgical margins in this anatomic region. Furthermore, propensity for local
      destruction and invasion can create significant morbidity.

PMID- 29324474
TI  - Active and Inactive Leg Hemodynamics during Sequential Single-Leg Interval
      Cycling.
AB  - INTRODUCTION: Leg order during sequential single-leg cycling (i.e., exercising
      both legs independently within a single session) may affect local muscular
      responses potentially influencing adaptations. This study examined the
      cardiovascular and skeletal muscle hemodynamic responses during double-leg and
      sequential single-leg cycling. METHODS: Ten young healthy adults (28 +/- 6 yr)
      completed six 1-min double-leg intervals interspersed with 1 min of passive
      recovery and, on a separate occasion, 12 (six with one leg followed by six with
      the other leg) 1-min single-leg intervals interspersed with 1 min of passive
      recovery. Oxygen consumption, heart rate, blood pressure, muscle oxygenation,
      muscle blood volume, and power output were measured throughout each session.
      RESULTS: Oxygen consumption, heart rate, and power output were not different
      between sets of single-leg intervals, but the average of both sets was lower than
      the double-leg intervals. Mean arterial pressure was higher during double-leg
      compared with sequential single-leg intervals (115 +/- 9 vs 104 +/- 9 mm Hg, P <
      0.05) and higher during the initial compared with second set of single-leg
      intervals (108 +/- 10 vs 101 +/- 10 mm Hg, P < 0.05). The increase in muscle
      blood volume from baseline was similar between the active single leg and the
      double leg (267 +/- 150 vs 214 +/- 169 MUM.cm, P = 0.26). The pattern of change
      in muscle blood volume from the initial to second set of intervals was
      significantly different (P < 0.05) when the leg was active in the initial (-52.3%
      +/- 111.6%) compared with second set (65.1% +/- 152.9%). CONCLUSIONS: These data
      indicate that the order in which each leg performs sequential single-leg cycling
      influences the local hemodynamic responses, with the inactive muscle influencing
      the stimulus experienced by the contralateral leg.

PMID- 29324475
TI  - Bilateral Cochlear Implants: Maximizing Expected Outcomes.
AB  - CASE: Sonia is a 4 years 1 month-year-old girl with Waardenburg syndrome and
      bilateral sensorineural hearing loss who had bilateral cochlear implants at 2
      years 7 months years of age. She is referred to Developmental-Behavioral
      Pediatrics by her speech/language pathologist because of concerns that her
      language skills are not progressing as expected after the cochlear implant. At
      the time of the implant, she communicated using approximately 20 signs and 1
      spoken word (mama). At the time of the evaluation (18 months after the implant)
      she had approximately 70 spoken words (English and Spanish) and innumerable signs
      that she used to communicate. She could follow 1-step directions in English but
      had more difficulty after 2-step directions.Sonia was born in Puerto Rico at 40
      weeks gestation after an uncomplicated pregnancy. She failed her newborn hearing
      test and was given hearing aids that did not seem to help.At age 2 years, Sonia,
      her mother, and younger sister moved to the United States where she was diagnosed
      with bilateral severe-to-profound hearing loss. Genetic testing led to a
      diagnosis of Waardenburg syndrome (group of genetic conditions that can cause
      hearing loss and changes in coloring [pigmentation] of the hair, skin, and eyes).
      She received bilateral cochlear implants 6 months later.Sonia's mother is
      primarily Spanish-speaking and mostly communicates with her in Spanish or with
      gestures but has recently begun to learn American Sign Language (ASL). In a
      preschool program at a specialized school for the deaf, Sonia is learning both
      English and ASL. Sonia seems to prefer to use ASL to communicate.Sonia receives
      speech and language therapy (SLT) 3 times per week (90 minutes total)
      individually in school and once per week within a group. She is also receiving
      outpatient SLT once per week. Therapy sessions are completed in English, with the
      aid of an ASL interpreter. Sonia's language scores remain low, with her receptive
      skills in the first percentile, and her expressive skills in the fifth
      percentile.During her evaluation in Developmental and Behavioral Pediatrics, an
      ASL interpreter was present, and the examiner is a fluent Spanish speaker.
      Testing was completed through a combination of English, Spanish, and ASL. Sonia
      seemed to prefer ASL to communicate, although she used some English words with
      errors of pronunciation. On the Beery Visual-Motor Integration Test, she obtained
      a standard score of 95. Parent and teacher rating scales were not significant for
      symptoms of attention-deficit/hyperactivity disorder.What factors are
      contributing to her slow language acquisition and how would you modify her
      treatment plan?

PMID- 29324476
TI  - Revisiting autologous transplantation in acute myeloid leukemia.
AB  - PURPOSE OF REVIEW: Autologous hematopoietic cell transplantation (auto-HCT) has
      been evaluated as a consolidation treatment for acute myeloid leukemia (AML) in
      the 1980s and 1990s. These prospective studies from large trials compared auto
      HCT with chemotherapy. A comparison was made also with allogeneic hematopoietic
      cell transplantation (allo-HCT). These studies reported a lower relapse rate with
      auto-HCT compared with chemotherapy, but without impact on the overall survival.
      A high transplant-related mortality in that era confounded the relevance of these
      data. RECENT FINDINGS: Several prospective studies and a plethora of
      retrospective registry data have confirmed the potent antileukemic therapy of
      auto-HCT compared with chemotherapy and, in some instances, have even challenged
      the presumed superiority of allo-HCT as the definitive therapy for certain
      patients with AML. SUMMARY: The aggregate of recent data, prospective and
      retrospective, strongly suggests an important role for auto-HCT, at least as the
      most potent nonimmunologic antileukemia therapy. The transplant-related mortality
      in 2017 is close to that expected from standard consolidation therapy leading to
      the conclusion that the role of auto-HCT needs to be rigorously revisited,
      preferably in prospective studies, to establish its precise role in the current
      era.

PMID- 29324478
TI  - Site of entry and surgical timing in infective endocarditis.

PMID- 29324477
TI  - Assuring Quality for Non-hospital-based Biologic Infusions in Pediatric
      Inflammatory Bowel Disease: A Clinical Report From the North American Society for
      Pediatric Gastroenterology, Hepatology and Nutrition.
AB  - The primary aim of this Clinical Report by the North American Society for
      Pediatric Gastroenterology, Hepatology and Nutrition is to provide formal
      guidance to pediatric gastroenterologists and clinicians, health systems, and
      insurance payers regarding home- and office-based infusions for biologic
      therapies in pediatric inflammatory bowel disease. Patients in North America are
      increasingly denied coverage by payers based on "place of service" codes at
      hospital-based infusion units where the treating clinicians primarily provide
      care. A task force with topic expertise generated 8 best practice recommendations
      to ensure quality of care for pediatric patients with inflammatory bowel disease
      receiving non-hospital-based biologic infusions. Pragmatic considerations
      discussed in this report include patient safety, pediatric-trained nurse
      availability, care coordination, patient-centeredness, shared liability,
      administrative support, clinical governance, and costs of care.

PMID- 29324479
TI  - A systematic review of epidemiology, treatment and prognosis of heart failure in
      adults in Ethiopia.
AB  - BACKGROUND: Systematic characterization of heart failure in adults in Ethiopia is
      lacking currently. In this review, we sought to summarize the available
      scientific evidence on the epidemiology, treatment and prognosis of heart failure
      in adults in Ethiopia. METHODS: A systematic review of PUBMED, EMBASE and SCOPUS
      was conducted for studies published between January 1990 and July 2017. Studies
      reporting on incidence, prevalence, treatment or prognosis of heart failure in
      individuals older than 14 years of age were included. RESULTS: The search yielded
      66 articles, out of which nine were found to be eligible for inclusion in this
      review. There are no studies reporting the incidence or prevalence of heart
      failure in the adult population in Ethiopia. There are, however, indications that
      heart failure might be a significant burden in the country, and typically affects
      middle-aged adults. Valvular heart disease, predominantly related to rheumatic
      heart disease, is the most commonly identified heart failure cause across the
      included studies. There are very limited data on treatment and prognosis.
      CONCLUSION: There is limited scientific evidence on the epidemiology, treatment
      and prognosis of heart failure in adults in Ethiopia. Further studies are needed
      for the better understanding of the burden and treatment of heart failure in the
      adult population in Ethiopia.

PMID- 29324480
TI  - Anesthesiology Board Certification Changes: A Real-time Example of "Assessment
      Drives Learning".

PMID- 29324481
TI  - Do Anesthetic Choices Signal Quality?

PMID- 29324482
TI  - Enhanced Needle Visibility by Micro Air Bubble Contrast in Ultrasound-guided
      Nerve Block.

PMID- 29324483
TI  - Advancing Patient Safety in Airway Management.

PMID- 29324484
TI  - Fear in Perspective.

PMID- 29324485
TI  - Bearing Witness to Anger and Loss.

PMID- 29324486
TI  - Fibrinolysis and antifibrinolytic treatment in the trauma patient.
AB  - PURPOSE OF REVIEW: The role of antifibrinolytics in trauma haemorrhage and early
      coagulopathy remains controversial with respect to patient selection, dosage,
      timing of treatment, and risk of thrombotic complications. This review presents
      our current understanding of the mechanisms of fibrinolysis in trauma, diagnostic
      evaluation, and the evidence base for treatment. RECENT FINDINGS: Excessive
      fibrinolysis following severe injury is a major component of acute traumatic
      coagulopathy and contributes to the high mortality from trauma haemorrhage. The
      protein C pathway, endothelial dysfunction, platelet activity, shock, and tissue
      injury are key to the development of hyper fibrinolysis in trauma. D-dimer and
      viscoelastic haemostatic assays (rotational thromboelastometry, TEG) remain the
      best available diagnostic modalities but have a number of limitations compared
      with plasma biomarkers of fibrinolytic activation, for example, plasmin-alpha2
      antiplasmin complex. Current evidence supports the continued empiric use of
      tranexamic acid in major trauma haemorrhage. SUMMARY: Improving the outcomes for
      bleeding trauma patients requires a deeper understanding of the mechanisms
      driving hyperfibrinolysis and the subsequent switch toward a prothrombotic state.
      Discovering the interplay between platelet activity, fibrinogen utilization, the
      immune response, and the fibrinolytic system may lead to development of novel
      therapeutics.

PMID- 29324487
TI  - Renal replacement therapy in critically ill patients: who, when, why, and how.
AB  - PURPOSE OF REVIEW: The increasing incidence of acute kidney injury has the
      immediate effect of a growing need for renal replacement therapy (RRT). Shedding
      light on the questions of who, when, why, and how RRT should be performed is
      difficult to accomplish because of ambiguous study results, poor quality
      evidence, and low standardization. RECENT FINDINGS: Critically ill patients are
      exposed to multiple factors known to deteriorate kidney function. Especially
      severe fluid overload is strongly associated with worse outcome and may be
      considered as a trigger for initiating RRT. In the absence of life-threatening
      complications, a strategy of early initiation of RRT might be most advantageous
      keeping in mind the potential adverse effects of RRT. By providing better
      hemodynamic stability and superior control of fluid balance continuous RRT is the
      first choice therapeutic tool as compared with intermittent techniques. The
      femoral and jugular veins are the preferred insertion sites for temporary
      catheters. Although data are still weak, there is some preliminary evidence that
      regional citrate anticoagulation is superior to systemic heparinization. SUMMARY:
      The best management of RRT is still a subject of controversy. Continuous RRT with
      regional citrate anticoagulation via a temporary catheter in a jugular vein is
      the recommended first choice treatment option in critically ill patients with
      acute kidney injury.

PMID- 29324488
TI  - Storage injury and blood transfusions in trauma patients.
AB  - PURPOSE OF REVIEW: The aim of the present review was to concisely summarize
      recent studies and current knowledge about effects of red blood cell storage
      injury in trauma patients. RECENT FINDINGS: Despite a pathophysiological
      rationale for older packed red blood cells (PRBCs) being associated with adverse
      events in the host organism, recent large clinical trials failed to show negative
      effects of transfusion with older PRBCs on clinically relevant outcomes in mixed
      patient population. However, there is a lack of well-designed randomized
      controlled trials focusing on the effects of storage lesion of PRBCs in trauma
      patients. SUMMARY: In the absence of specific evidence for trauma patients, we
      recommend to continue with a conservative transfusion regime and standard of care
      blood banking practice of using older PRBCs first.

PMID- 29324489
TI  - Comparing Methods for Cardiac Output: Intraoperatively Doppler-Derived Cardiac
      Output Measured With 3-Dimensional Echocardiography Is Not Interchangeable With
      Cardiac Output by Pulmonary Catheter Thermodilution.
AB  - BACKGROUND: Estimation of cardiac output (CO) is essential in the treatment of
      circulatory unstable patients. CO measured by pulmonary artery catheter
      thermodilution is considered the gold standard but carries a small risk of severe
      complications. Stroke volume and CO can be measured by transesophageal
      echocardiography (TEE), which is widely used during cardiac surgery. We
      hypothesized that Doppler-derived CO by 3-dimensional (3D) TEE would agree well
      with CO measured with pulmonary artery catheter thermodilution as a reference
      method based on accurate measurements of the cross-sectional area of the left
      ventricular outflow tract. METHODS: The primary aim was a systematic comparison
      of CO with Doppler-derived 3D TEE and CO by thermodilution in a broad population
      of patients undergoing cardiac surgery. A subanalysis was performed comparing
      cross-sectional area by TEE with cardiac computed tomography (CT) angiography.
      Sixty-two patients, scheduled for elective heart surgery, were included; 1 was
      subsequently excluded for logistic reasons. Inclusion criteria were coronary
      artery bypass surgery (N = 42) and aortic valve replacement (N = 19). Exclusion
      criteria were chronic atrial fibrillation, left ventricular ejection fraction
      below 0.40 and intracardiac shunts. Nineteen randomly selected patients had a
      cardiac CT the day before surgery. All images were stored for blinded post hoc
      analyses, and Bland-Altman plots were used to assess agreement between
      measurement methods, defined as the bias (mean difference between methods),
      limits of agreement (equal to bias +/- 2 standard deviations of the bias), and
      percentage error (limits of agreement divided by the mean of the 2 methods).
      Precision was determined for the individual methods (equal to 2 standard
      deviations of the bias between replicate measurements) to determine the
      acceptable limits of agreement. RESULTS: We found a good precision for Doppler
      derived CO measured by 3D TEE, but although the bias for Doppler-derived CO by 3D
      compared to thermodilution was only 0.3 L/min (confidence interval, 0.04-0.58),
      there were wide limits of agreement (-1.8 to 2.5 L/min) with a percentage error
      of 55%. Measurements of cross-sectional area by 3D TEE had low bias of -0.27 cm
      (confidence interval, -0.45 to -0.08) and a percentage error of 18% compared to
      cardiac CT angiography. CONCLUSIONS: Despite low bias, the wide limits of
      agreement of Doppler-derived CO by 3D TEE compared to CO by thermodilution will
      limit clinical application and can therefore not be considered interchangeable
      with CO obtained by thermodilution. The lack of agreement is not explained by
      lack of agreement of the 3D technique.

PMID- 29324490
TI  - Balancing Infection Control and Environmental Protection as a Matter of Patient
      Safety: The Case of Laryngoscope Handles.

PMID- 29324491
TI  - Validation of a Second-Generation Near-Infrared Spectroscopy Monitor in Children
      With Congenital Heart Disease.
AB  - BACKGROUND: Cerebral oximetry using near-infrared spectroscopy is a noninvasive
      optical technology to detect cerebral hypoxia-ischemia and develop interventions
      to prevent and ameliorate hypoxic brain injury. Cerebral oximeters are calibrated
      and validated by comparison of the near-infrared spectroscopy-measured cerebral
      O2 saturation (SctO2) to a "field" or reference O2 saturation (REF CX) calculated
      as a weighted average from arterial and jugular bulb oxygen saturations. In this
      study, we calibrated and validated the second-generation, 5 wavelength, FORE
      SIGHT Elite with the medium sensor (source-detector separation 12 and 40 mm) for
      measurement of SctO2 in children with congenital heart disease. METHODS: After
      institutional review board approval and written informed consent, 63 children
      older than 1 month and >=2.5 kg scheduled for cardiac catheterization were
      enrolled. Self-adhesive FORE-SIGHT Elite medium sensors were placed on the right
      and left sides of the forehead. Blood samples for calculation of REF CX were
      drawn simultaneously from the aorta or femoral artery and the jugular bulb before
      (T1) and shortly after (T2) baseline hemodynamic measurements. FORE-SIGHT Elite
      SctO2 measurements were compared to the REF CX (REF CX = [0.3 SaO2] + [0.7
      SjbO2]) using Deming regression, least squares linear regression, and Bland
      Altman analysis. RESULTS: Sixty-one subjects (4.5 [standard deviation 4.4] years
      of age; 17 [standard deviation 13] kg, male 56%) completed the study protocol.
      Arterial oxygen saturation ranged from 64.7% to 99.1% (median 96.0%), jugular
      bulb venous oxygen saturation from 34.1% to 88.1% (median 68.2%), the REF CX from
      43.8% to 91.4% (median 76.9%), and the SctO2 from 47.8% to 90.8% (median 76.3%).
      There was a high degree of correlation in SctO2 between the right and left
      sensors at a given time point (within subject between sensor correlation r = 0.91
      and 95% confidence interval [CI], 0.85-0.94) or between T1 and T2 for the right
      and left sensors (replicates, within subject between time point correlation r =
      0.95 and 95% CI, 0.92-0.96). By Deming regression, the estimated slope was 0.966
      (95% CI, 0.786-1.147; P = .706 for testing against null hypothesis of slope = 1)
      with a y intercept of 2.776 (95% CI, -11.102 to 16.654; P = .689). The
      concordance correlation coefficient was 0.873 (95% CI, 0.798-0.922). Bland-Altman
      analysis for agreement between SctO2 and REF CX that accounted for repeated
      measures (both in times and sensors) found a bias of -0.30% (95% limits of
      agreement: -10.56% to 9.95%). CONCLUSIONS: This study calibrated and validated
      the FORE-SIGHT Elite tissue oximeter to accurately measure SctO2 in pediatric
      patients with the medium sensor.

PMID- 29324492
TI  - Life Cycle Assessment and Costing Methods for Device Procurement: Comparing
      Reusable and Single-Use Disposable Laryngoscopes.
AB  - BACKGROUND: Traditional medical device procurement criteria include efficacy and
      safety, ease of use and handling, and procurement costs. However, little
      information is available about life cycle environmental impacts of the
      production, use, and disposal of medical devices, or about costs incurred after
      purchase. Reusable and disposable laryngoscopes are of current interest to
      anesthesiologists. Facing mounting pressure to quickly meet or exceed conflicting
      infection prevention guidelines and oversight body recommendations, many
      institutions may be electively switching to single-use disposable (SUD) rigid
      laryngoscopes or overcleaning reusables, potentially increasing both costs and
      waste generation. This study provides quantitative comparisons of environmental
      impacts and total cost of ownership among laryngoscope options, which can aid
      procurement decision making to benefit facilities and public health. METHODS: We
      describe cradle-to-grave life cycle assessment (LCA) and life cycle costing (LCC)
      methods and apply these to reusable and SUD metal and plastic laryngoscope
      handles and tongue blade alternatives at Yale-New Haven Hospital (YNHH). The US
      Environmental Protection Agency's Tool for the Reduction and Assessment of
      Chemical and other environmental Impacts (TRACI) life cycle impact assessment
      method was used to model environmental impacts of greenhouse gases and other
      pollutant emissions. RESULTS: The SUD plastic handle generates an estimated 16-18
      times more life cycle carbon dioxide equivalents (CO2-eq) than traditional low
      level disinfection of the reusable steel handle. The SUD plastic tongue blade
      generates an estimated 5-6 times more CO2-eq than the reusable steel blade
      treated with high-level disinfection. SUD metal components generated much higher
      emissions than all alternatives. Both the SUD handle and SUD blade increased life
      cycle costs compared to the various reusable cleaning scenarios at YNHH. When
      extrapolated over 1 year (60,000 intubations), estimated costs increased between
      $495,000 and $604,000 for SUD handles and between $180,000 and $265,000 for SUD
      blades, compared to reusables, depending on cleaning scenario and assuming 4000
      (rated) uses. Considering device attrition, reusable handles would be more
      economical than SUDs if they last through 4-5 uses, and reusable blades 5-7 uses,
      before loss. CONCLUSIONS: LCA and LCC are feasible methods to ease interpretation
      of environmental impacts and facility costs when weighing device procurement
      options. While management practices vary between institutions, all standard
      methods of cleaning were evaluated and sensitivity analyses performed so that
      results are widely applicable. For YNHH, the reusable options presented a
      considerable cost advantage, in addition to offering a better option
      environmentally. Avoiding overcleaning reusable laryngoscope handles and blades
      is desirable from an environmental perspective. Costs may vary between
      facilities, and LCC methodology demonstrates the importance of time-motion labor
      analysis when comparing reusable and disposable device options.

PMID- 29324493
TI  - Anesthesia-Guided Palliative Care in the Perioperative Surgical Home Model.

PMID- 29324494
TI  - Myocardial Protection by Glucose-Insulin-Potassium in Moderate- to High-Risk
      Patients Undergoing Elective On-Pump Cardiac Surgery: A Randomized Controlled
      Trial.
AB  - BACKGROUND: Low cardiac output syndrome is a main cause of death after cardiac
      surgery. We sought to assess the impact of glucose-insulin-potassium (GIK) to
      enhance myocardial protection in moderate- to high-risk patients undergoing on
      pump heart surgery. METHODS: A randomized controlled trial was performed in adult
      patients (Bernstein-Parsonnet score >7) scheduled for elective aortic valve
      replacement and/or coronary artery bypass surgery. Patients were randomized to
      GIK (20 IU of insulin, 10 mEq of potassium chloride in 50 mL of glucose 40%) or
      saline infusion given over 60 minutes on anesthetic induction. The primary end
      point was postcardiotomy ventricular dysfunction (PCVD), defined as new/worsening
      left ventricular dysfunction requiring inotropic support (>=120 minutes).
      Secondary end points were the intraoperative changes in left ventricular function
      as assessed by transoesophageal echocardiography, postoperative troponin levels,
      cardiovascular and respiratory complications, and intensive care unit and
      hospital length of stay. RESULTS: From 224 randomized patients, 222 were analyzed
      (112 and 110 in the placebo and GIK groups, respectively). GIK pretreatment was
      associated with a reduced occurrence of PCVD (risk ratio [RR], 0.41; 95%
      confidence interval [CI], 0.25-0.66). In GIK-treated patients, the left systolic
      ventricular function was better preserved after weaning from bypass, plasma
      troponin levels were lower on the first postoperative day (2.9 ng.mL
      [interquartile range {IQR}, 1.5-6.6] vs 4.3 ng.mL [IQR, 2.4-8.2]), and
      cardiovascular (RR, 0.69; 95% CI, 0.50-0.89) and respiratory complications (RR,
      0.5; 95% CI, 0.38-0.74) were reduced, along with a shorter length of stay in
      intensive care unit (3 days [IQR, 2-4] vs 3.5 days [IQR, 2-7]) and in hospital
      (14 days [IQR, 11-18.5] vs 16 days [IQR, 12.5-23.5]), compared with placebo
      treated patients. CONCLUSIONS: GIK pretreatment was shown to attenuate PCVD and
      to improve clinical outcome in moderate- to high-risk patients undergoing on-pump
      cardiac surgery.

PMID- 29324495
TI  - Intravenously Administered Lidocaine and Magnesium During Thyroid Surgery in
      Female Patients for Better Quality of Recovery After Anesthesia.
AB  - BACKGROUND: Although systemic lidocaine and magnesium have been widely studied as
      perioperative analgesic adjuvants, they have been rarely evaluated with respect
      to recovery quality under the same conditions. We compared the quality of
      recovery 40 (QoR-40) scores of female patients who received intravenous
      lidocaine, magnesium, and saline during thyroidectomy to investigate their
      effects on comprehensive recovery from anesthesia. METHODS: In this prospective,
      double-blind trial, 135 female patients scheduled for open thyroidectomy were
      randomly assigned to the lidocaine group (group L), magnesium group (group M), or
      control group (group C). Immediately after induction, lidocaine (2 mg/kg for 15
      minutes followed by 2 mg/kg/h) was administered in group L and magnesium sulfate
      (20 mg/kg over 15 minutes followed by 20 mg/kg/h) was administered in group M.
      Group C received an equivalent volume of saline. The QoR-40 survey was conducted
      on postoperative days 1 and 2. RESULTS: The mean global QoR-40 scores on
      postoperative day 1 were 186.3 (standard deviation, 5.5) in group L, 184.3 (4.7)
      in group M, and 179.4 (17.8) in group C, and there was a significant difference
      only between group L and group C (mean difference, 6.9; adjusted P = .018). Among
      the 5 dimensions of QoR-40, emotional state, physical comfort, and pain were
      superior in group L compared to group C. CONCLUSIONS: Lidocaine administered
      intravenously during anesthesia led to better quality of postoperative recovery
      measured by QoR-40 compared with the group C. Magnesium was found to be
      insufficient to induce any significant improvement with the dose used in the
      present study.

PMID- 29324496
TI  - Efficacy of Ultrasound-Guided Serratus Plane Block on Postoperative Quality of
      Recovery and Analgesia After Video-Assisted Thoracic Surgery: A Randomized,
      Triple-Blind, Placebo-Controlled Study.
AB  - BACKGROUND: The optimal regional technique for analgesia and improved quality of
      recovery after video-assisted thoracic surgery (a procedure associated with
      considerable postoperative pain) has not been established. The main objective in
      this study was to compare quality of recovery in patients undergoing serratus
      plane block (SPB) with either ropivacaine or normal saline on the first
      postoperative day. Secondary outcomes were analgesic outcomes, including
      postoperative pain intensity and opioid consumption. METHODS: Ninety patients
      undergoing video-assisted thoracic surgery were randomized to receive ultrasound
      guided SPB with 0.4 mL/kg of either 0.375% ropivacaine (SPB group) or normal
      saline (control group) after anesthetic induction. The primary outcome was the 40
      item Quality of Recovery (QoR-40) score at 24 hours after surgery. The QoR-40
      questionnaire was completed by patients the day before surgery and on
      postoperative days 1 and 2. Pain scores, opioid consumption, and adverse events
      were assessed for 2 days postoperatively. RESULTS: Eighty-five patients completed
      the study: 42 in the SPB group and 43 in the control group. The global QoR-40
      scores on both postoperative days 1 and 2 were significantly higher in the SPB
      group than in the control group (estimated mean difference 8.5, 97.5% confidence
      interval [CI], 2.1-15.0, and P = .003; 8.5, 97.5% CI, 2.0-15.1, and P = .004,
      respectively). The overall mean difference between the SPB and control groups was
      8.5 (95% CI, 3.3-13.8; P = .002). Pain scores at rest and opioid consumption were
      significantly lower up to 6 hours after surgery in the SPB group than in the
      control group. Cumulative opioid consumption was significantly lower up to 24
      hours postoperatively in the SPB group. CONCLUSIONS: Single-injection SPB with
      ropivacaine enhanced the quality of recovery for 2 days postoperatively and
      improved postoperative analgesia during the early postoperative period in
      patients undergoing video-assisted thoracic surgery.

PMID- 29324498
TI  - Five Steps to Successfully Implement and Evaluate Propensity Score Matching in
      Clinical Research Studies.
AB  - In clinical research, the gold standard level of evidence is the randomized
      controlled trial (RCT). The availability of nonrandomized retrospective data is
      growing; however, a primary concern of analyzing such data is comparability of
      the treatment groups with respect to confounding variables. Propensity score
      matching (PSM) aims to equate treatment groups with respect to measured baseline
      covariates to achieve a comparison with reduced selection bias. It is a valuable
      statistical methodology that mimics the RCT, and it may create an "apples to
      apples" comparison while reducing bias due to confounding. PSM can improve the
      quality of anesthesia research and broaden the range of research opportunities.
      PSM is not necessarily a magic bullet for poor-quality data, but rather may allow
      the researcher to achieve balanced treatment groups similar to a RCT when high
      quality observational data are available. PSM may be more appealing than the
      common approach of including confounders in a regression model because it allows
      for a more intuitive analysis of a treatment effect between 2 comparable
      groups.We present 5 steps that anesthesiologists can use to successfully
      implement PSM in their research with an example from the 2015 Pediatric National
      Surgical Quality Improvement Program: a validated, annually updated surgery and
      anesthesia pediatric database. The first step of PSM is to identify its
      feasibility with regard to the data at hand and ensure availability of data on
      any potential confounders. The second step is to obtain the set of propensity
      scores from a logistic regression model with treatment group as the outcome and
      the balancing factors as predictors. The third step is to match patients in the 2
      treatment groups with similar propensity scores, balancing all factors. The
      fourth step is to assess the success of the matching with balance diagnostics,
      graphically or analytically. The fifth step is to apply appropriate statistical
      methodology using the propensity-matched data to compare outcomes among treatment
      groups.PSM is becoming an increasingly more popular statistical methodology in
      medical research. It often allows for improved evaluation of a treatment effect
      that may otherwise be invalid due to a lack of balance between the 2 treatment
      groups with regard to confounding variables. PSM may increase the level of
      evidence of a study and in turn increases the strength and generalizability of
      its results. Our step-by-step approach provides a useful strategy for
      anesthesiologists to implement PSM in their future research.

PMID- 29324497
TI  - Complications Associated With Mortality in the National Surgical Quality
      Improvement Program Database.
AB  - BACKGROUND: Attributing causes of postoperative mortality is challenging, as
      death may be multifactorial. A better understanding of complications that occur
      in patients who die is important, as it allows clinicians to focus on the most
      impactful complications. We sought to determine the postoperative complications
      with the strongest independent association with 30-day mortality. METHODS: Data
      were obtained from the 2012-2013 National Surgical Quality Improvement Program
      Participant Use Data Files. All inpatient or admit day of surgery cases were
      eligible for inclusion in this study. A multivariable least absolute shrinkage
      and selection operator regression analysis was used to adjust for patient pre-
      and intraoperative risk factors for mortality. Attributable mortality was
      calculated using the population attributable fraction method: the ratio between
      the odds ratio for mortality and a given complication in the population. Patients
      were separated into 10 age groups to facilitate analysis of age-related
      differences in mortality. RESULTS: A total of 1,195,825 patients were analyzed,
      and 9255 deceased within 30 days (0.77%). A complication independently associated
      with attributable mortality was found in 1887 cases (20%). The most common causes
      of attributable mortality (attributable deaths per million patients) were
      bleeding (n = 368), respiratory failure (n = 358), septic shock (n = 170), and
      renal failure (n = 88). Some complications, such as urinary tract infection and
      pneumonia, were associated with attributable mortality only in older patients.
      DISCUSSION: Additional resources should be focused on complications associated
      with the largest attributable mortality, such as respiratory failure and
      infections. This is particularly important for complications disproportionately
      impacting younger patients, given their longer life expectancy.

PMID- 29324499
TI  - Adding to Our Competitive Advantage: Making the Case for Teaching Communication
      and Professionalism.

PMID- 29324500
TI  - Hydroxyethyl Starch 130/0.4 and Its Impact on Perioperative Outcome: A Propensity
      Score Matched Controlled Observation Study.
AB  - BACKGROUND: Adverse effects of hydroxyethyl starches (HESs) have been verified in
      patients suffering from sepsis or kidney disease, but not in surgical patients at
      large. The investigation aimed to determine whether the use of HES 130/0.4 was
      associated with the incidence of acute postinterventional adverse events compared
      to Ringer's acetate alone in a perioperative setting. METHODS: This propensity
      score matched, controlled observational study was performed in a single-centre
      university hospital. The perioperative data of 9085 patients were analyzed. Group
      matching was based on 13 categories including demographic data, type of
      procedure, and 5 preexisting comorbidities. Duration of procedure and
      intraoperative transfusion requirements were integrated in the matching process
      to reduce selection and indication bias. The primary outcome was incidence of
      postoperative kidney failure. Secondary outcomes were in-hospital mortality,
      fluid requirements, blood loss, hemodynamic stability, and the need for
      postoperative intensive care unit (ICU) treatment. RESULTS: The administration of
      HES 130/0.4 was not associated with an increased frequency of postoperative
      kidney failure. In-hospital mortality (Ringer's acetate: 2.58%; HES 130/0.4:
      2.68%) and the need for ICU care (Ringer's acetate: 30.5%; HES 130/0.4: 34.3%)
      did not differ significantly between groups. Significant intergroup differences
      were observed for mean blood loss (Ringer's acetate: 406 +/- 821 mL; HES 130/0.4:
      867 +/- 1275 mL; P < .001) and median length of hospital stay (Ringer's acetate:
      10.5 (5/17) days; HES 130/0.4: 12.0 (8/19) days; P < .001). CONCLUSIONS: An
      association between intraoperative HES therapy and postoperative kidney failure
      was not observed in a mixed cohort of elective surgical patients. In addition,
      HES 130/0.4 was not associated with an increased morbidity or the need for ICU
      therapy in this propensity score matched study.

PMID- 29324501
TI  - Nonpharmacologic Management of Acute Singultus (Hiccups).

PMID- 29324502
TI  - In Response.

PMID- 29324503
TI  - alpha-Asarone Alleviated Chronic Constriction Injury-Induced Neuropathic Pain
      Through Inhibition of Spinal Endoplasmic Reticulum Stress in an Liver X Receptor
      Dependent Manner.
AB  - BACKGROUND: Neuropathic pain is an intractable and complex disease. Recent
      studies have shown a close relationship between endoplasmic reticulum (ER) stress
      and neuropathic pain. Here, we investigated the effect of alpha-asarone, an ER
      stress inhibitor, on chronic constriction injury (CCI)-induced neuropathic pain.
      METHODS: Two parts were included in this study. In part 1, rats were assigned to
      7 groups: the sham group, the sham + alpha-asarone 20 mg/kg group, the CCI group,
      the CCI + vehicle group, the CCI + alpha-asarone 5 mg/kg group, the CCI + alpha
      asarone 10 mg/kg group, and the CCI + alpha-asarone 20 mg/kg group. After
      surgery, the rats were treated with alpha-asarone or normal saline daily. Pain
      thresholds were measured, and samples of the L3-6 spinal cord were taken for
      western blotting and immunofluorescence on day 7. In part 2, rats were
      intrathecally implanted with PE-10 tubes and divided into 4 groups: the CCI +
      alpha-asarone 20 mg/kg group, the CCI + alpha-asarone 20 mg/kg + vehicle group,
      the CCI + alpha-asarone 20 mg/kg + SR9243 group, and the CCI group. Five rats in
      each group were separated for behavioral tests 1 hour after intrathecal
      injection. The rest of them were killed for western blotting on day 7. RESULTS:
      In this study, CCI surgery significantly induced mechanical allodynia and thermal
      hyperalgesia. CCI surgery significantly induced activation of ER stress (PERK
      eIF2alpha, IRE1alpha, CHOP, and XBP-1s) in rats. However, treatment with 20 mg/kg
      of alpha-asarone significantly alleviated CCI-induced activation of ER stress.
      Behavioral results showed that daily treatment with 20 mg/kg of alpha-asarone
      significantly alleviated CCI-induced nociceptive behaviors, on day 7 (mechanical
      allodynia, P = .016, 95% confidence interval, 0.645-5.811; thermal hyperalgesia,
      P = .012, 95% confidence interval, 0.860-6.507). Furthermore, alpha-asarone
      induced upregulated expression of liver X receptor beta (LXRbeta) and downstream
      proteins in the spinal cord. The LXR antagonist SR9243 completely inhibited the
      anti-ER stress and antinociceptive effects of alpha-asarone in rats. CONCLUSIONS:
      alpha-Asarone relieved CCI-induced neuropathic pain in an LXR-dependent manner.
      alpha-Asarone may be a potential agent for treatment of neuropathic pain.

PMID- 29324504
TI  - Aspergillus and other respiratory fungal infections in the ICU: diagnosis and
      management.
AB  - PURPOSE OF REVIEW: Filamentous fungi respiratory infections, namely because of
      Aspergillus, Mucorales, Fusarium, or Scedosporium, show rising incidence and
      occur more in populations which are not classically immunosuppressed. This and
      their persistent dismal prognosis are the focus of this review. RECENT FINDINGS:
      Both an early diagnosis, rooted on a high level of suspicion and based on
      clinical picture, radiology, cultural microbiological exams, fungal biomarkers,
      PCR and biopsy, and an early therapy, including immunorecovery, whenever
      possible, good antifungal selection, and surgery for source control, are
      paramount to maximize the outcome in these diseases. An evolving antifungal
      armamentarium and a more Pharmacokinetics/Pharmacodynamics-based antifungal
      prescription may help to improve the prognosis. SUMMARY: Improved awareness of
      these infections may increase the level of suspicion, promoting early diagnosis
      and treatment, ideally supported with expert stewardship.

PMID- 29324505
TI  - When to switch to an oral treatment and/or to discharge a patient with skin and
      soft tissue infections.
AB  - PURPOSE OF REVIEW: Skin and soft tissue infections prevalence is increasing and
      represent a frequent cause of hospital admission. New guidelines have become
      available in order to better define these infections and their response to
      antimicrobial treatment. Gram-positive bacteria, in particular Staphylococcus
      aureus, remain the most frequently isolated pathogens in skin and soft tissue
      infections. To treat complicated forms and infections caused by drug-resistant
      bacteria, hospital admission and administration of intravenous antibiotics are
      often required, impacting on healthcare costs and patients' morbidity. RECENT
      FINDINGS: New therapeutic options offer efficacy against drug-resistant Gram
      positive bacteria as well as potential to favor early patients' discharge,
      including the possibility for intravenous to oral switch and infrequent drug
      administration because of prolonged drug half-life. Although data from real-world
      studies on new antimicrobials is awaited, clinicians need clear direction on how
      to optimize the treatment of skin and soft tissue infections in order to avoid
      prolonged hospitalizations and extra costs. Early assessment of patient's
      clinical conditions and response to treatment appear useful in order to
      facilitate patients' discharge. SUMMARY: We have reported the evidence for early
      intravenous to oral switch and early hospital discharge for patients with skin
      and soft tissue infections. New therapeutic options that represent promising
      tools in promoting an optimized management of these infections have also been
      reviewed.

PMID- 29324506
TI  - A pilot mixed-methods evaluation of MS INFoRm: a self-directed fatigue management
      resource for individuals with multiple sclerosis.
AB  - Fatigue management interventions for individuals with multiple sclerosis (MS)
      often feature structured programmes requiring repeated, in-person attendance that
      is not possible for all individuals. We sought to determine whether MS INFoRm, a
      self-directed fatigue management resource for individuals with MS, was worth
      further, more rigorous evaluation. Our indicators of worthiness were actual use
      of the resource by participants over 3 months, reductions in fatigue impact and
      increases in self-efficacy, and participant reports of changes in fatigue
      management knowledge and behaviours. This was a single-group, mixed-methods,
      before-after pilot study in individuals with MS reporting mild to moderate
      fatigue. Thirty-five participants were provided with MS INFoRm by a USB flash
      drive to use at home for 3 months, on their own volition. Twenty-three
      participants completed all standardized questionnaires, semi-structured
      interviews and study process measures. Participants reported actively using MS
      INFoRm over the 3-month study period (median total time spent using MS INFoRm=315
      min) as well as significantly lower overall fatigue impact (Modified Fatigue
      Impact Scale: t=2.6, P=0.01), increased knowledge of MS fatigue (z=-2.8, P=0.01)
      and greater confidence in managing MS fatigue (z=-3.3, P=0.001). Individuals with
      significant reductions in fatigue impact also reported behavioural changes
      including tracking fatigue, better communication with others, greater awareness,
      improved quality of life and being more proactive. This study provides evidence
      that further rigorous evaluation of MS INFoRm, a self-directed resource for
      managing fatigue, is worth pursuing.

PMID- 29324507
TI  - Determining when to stop antiepileptic drug treatment.
AB  - PURPOSE OF REVIEW: As the number of patients diagnosed with epilepsy continues to
      rise and the pharmacological and device-based treatment options for epilepsy
      increase, determining when to stop antiepileptic drug (AED) treatment continues
      to be an important issue for patient management and counseling. RECENT FINDINGS:
      This review focuses on outcomes following AED withdrawal in seizure-free adults
      with epilepsy. Practical considerations are also discussed because, despite the
      importance of this topic, relatively little progress has been made in the past
      year regarding the identification of patients whose risk for recurrent seizures
      after AED withdrawal is no higher than that of the general population. SUMMARY:
      Although articles in the past year have updated the debates about whether and
      when to discontinue AEDs in seizure-free adults and have suggested potential
      utility for electroencephalograms as a prognostic tool for AED reduction as well
      as for an AED withdrawal risk calculator, decisions about AED withdrawal should
      still be based on the known risks and consequences of seizure recurrence and be
      made following well documented discussions between doctor and patient/carer.

PMID- 29324508
TI  - Comparison of human coagulation factor VIII expression directed by
      cytomegalovirus and mammary gland-specific promoters in HC11 cells and transgenic
      mice: Retraction.

PMID- 29324509
TI  - Investigating the Relationship of the Functional Gait Assessment to
      Spatiotemporal Parameters of Gait and Quality of Life of Individuals With Stroke.
AB  - BACKGROUND AND PURPOSE: Walking in the community is an important aspect of
      independence and quality of life (QOL) that poses challenges for individuals with
      stroke. This study investigated whether performance on the Functional Gait
      Assessment (FGA) differentiated spatiotemporal gait parameters, QOL, and fall
      history of community-ambulating individuals with stroke. We hypothesized that
      those scoring higher on the FGA would present with better gait speed and cadence,
      stride width and length, and improved load time on the paretic limb, report a
      higher QOL, and be less likely to have a fall history than those who scored lower
      on the FGA. METHODS: Participants were screened for cognitive impairment and the
      ability to walk independently. Participant demographics and stroke
      characteristics were recorded. The Falls Risk for Older People in the Community
      (FROP-Com) screening tool determined whether the participant had incurred 1 or
      more falls within the preceding 12 months. The FGA provided a composite measure
      of gait with varied walking tasks challenging different aspects of walking. The
      total score was recorded. The GAITRite instrumented-walkway was used to acquire
      high-resolution footfall data during performance of the first 9 FGA walking
      tasks. The Assessment of Quality of Life-6D (AQoL-6D) was used to measure health
      related QOL across the domains of independent living, mental health, coping,
      relationships, pain, and senses. Pearson and Spearman correlations were used to
      check for correlations between FGA score and the demographic characteristics,
      AQoL-6D scores, and 12-month fall history. Pearson correlations were used to
      check for correlations between FGA score and multiple spatiotemporal gait
      parameters for each FGA item. RESULTS AND DISCUSSION: A sample of 29 volunteers
      who were community-ambulating individuals with stroke was recruited. Participants
      had a mean age of 62.31 (10.89) years, mean time since stroke of 3.78 (4.10)
      years, and included both males and females (52% male). Individuals presented with
      both left- and right-sided strokes. FGA score correlated positively with
      velocity, cadence, and step length, and negatively with stride width, double
      support percent, and single-support variability (P = .001 to P = .031). FGA score
      correlated positively with the AQoL-6D dimension of independent living. FGA score
      correlated significantly with the FROP-Com screening tool predicted fall risk,
      but not with fall history. CONCLUSIONS: The FGA is a clinical measure of
      functional gait performance that reflected spatiotemporal gait parameters and
      ability of individuals with chronic stroke to live independently. The FGA could
      be used to target interventions to improve functional gait performance of
      individuals with chronic stroke.

PMID- 29324510
TI  - Reliability and Validity of Computerized Force Platform Measures of Balance
      Function in Healthy Older Adults.
AB  - BACKGROUND AND PURPOSE: Postural control declines with aging and is an
      independent risk factor for falls in older adults. Objective examination of
      balance function is warranted to direct fall prevention strategies. Force
      platform (FP) systems provide quantitative measures of postural control and
      analysis of different aspects of balance. The purpose of this study was to
      examine the reliability and validity of FP measures in healthy older adults.
      METHODS: This study enrolled 46 healthy elderly adults, mean age 67.67 (5.1)
      years, who had no history of falls. They were assessed on 3 standardized tests on
      the NeuroCom Equitest FP system: limits of stability (LOS), motor control test
      (MCT), and sensory organization test (SOT). The test battery was administered
      twice within a 10-day period for test-retest reliability; intraclass correlation
      coefficients (ICCs), standard error of measurement (SEM), and minimal detectable
      change based on a 95% confidence interval (MDC95) were calculated. FP measures
      were compared with criterion clinical balance (Mini-BESTest and Functional Gait
      Assessment) and gait (10-m walk and 6-minute walk) measures to examine concurrent
      validity using Pearson correlation coefficients. Multiple linear regression
      analysis examined whether age and activity level were associated with FP
      performance. The alpha level was set at P < .05. RESULTS: SOT composite
      equilibrium scores, MCT average latency, and LOS end point excursion measures all
      demonstrated excellent test-retest reliability (ICC = 0.90, 0.85, and 0.77,
      respectively), whereas moderate to good reliability was found for SOT vestibular
      ratio score (ICC = 0.71). There was large variability in performance in this
      healthy elderly cohort, resulting in relatively large MDC95 for these measures,
      especially for the LOS test. Fair correlations were found between LOS end point
      excursion and clinical balance and gait measures (r = 0.31-0.49), and between MCT
      average latency and gait measures only (r = -0.32). No correlations were found
      between SOT measures and clinical balance and gait measures. Age was only
      marginally significantly (P = .055) associated with LOS end point excursion but
      was not associated with SOT or MCT measures, and activity level was not
      associated with any of the FP measures. CONCLUSION: FP measures provided reliable
      information on balance function in healthy older adults; however, small learning
      effects were evident, particularly for the SOT. The SEM and MDC95 for the LOS and
      SOT measures were relatively large for this healthy elderly cohort. A
      relationship between FP measures, which assess underlying balance mechanisms, and
      clinical balance and gait measures was not strongly supported in this study.
      Further research is needed to justify the value of adding FP measures to a test
      battery for balance assessment in older adults without a history of falls.

PMID- 29324511
TI  - Evolutionary Improvements in the Jarvik 2000 Left Ventricular Assist Device.
AB  - Mechanical circulatory support devices experience a wide range of operating
      conditions during patient use. Since its first implant in June 2000, the Jarvik
      2000 left ventricular assist device has witnessed systematic stepwise
      modifications to reduce the risk of serious adverse events and improve patient
      outcomes. Over time, clinical experience revealed a number of low-incidence
      failure modes that presented opportunities for improvement. Design changes have
      included, but are not limited to, a Y cable to permit battery changes without
      pump stoppage, increased pull strength of external cables from 35 to 200 lbs, an
      intermittent low-speed controller to improve aortic root washout, sintered
      titanium microsphere surface on the pump housing to prevent apical thrombus, and
      novel cone bearings to reduce thrombus formation. In summary, real world
      conditions challenge devices in ways that laboratory or animal experiments do
      not. Thorough case reviews have led to many improvements as the Jarvik 2000
      continues through its second decade of implants.

PMID- 29324512
TI  - Exercise Capacity in Patients with the Total Artificial Heart.
AB  - There is a dearth of information regarding the functional abilities of patients
      with the total artificial heart (TAH). Increased utilization of the TAH and
      patient discharge to home with the portable unit necessitates a shift in focus to
      quality of life, which includes quantifying and ultimately optimizing functional
      capacity. To date, only single-patient case studies have described the exercise
      response of the TAH patient. Fourteen patients with the TAH underwent
      cardiopulmonary exercise testing with concurrent analysis of TAH device function.
      All device settings remained fixed during testing. Peak oxygen consumption (VOO2;
      0.872 L/min [interquartile range (IQR) = 0.828-1.100 L/min]), percent predicted
      peak VOO2 (36% [IQR = 32-42%]), and ventilatory anaerobic threshold (0.695 L/min
      [IQR = 0.542-0.845 L/min]) were markedly reduced in the TAH compared with
      predicted normal values. Determinants of VOO2 using device-generated hemodynamics
      revealed a blunted cardiac output (+9% increase) and exaggerated oxygen
      extraction with exercise. Peak VOO2 strongly correlated with resting (R = +0.548,
      p = 0.045), ventilatory anaerobic threshold (R = +0.780, p = 0.001), and peak
      exercise cardiac output (R = +0.672, p = 0.008). Patients with the TAH have
      significantly impaired exercise performance. The limitations to cardiopulmonary
      exercise testing performance appear to be related to limited ability of the pump
      to modulate output for activity and reduced oxygen carrying capacity.

PMID- 29324513
TI  - The Functional Immune Response of Patients on Extracorporeal Life Support.
AB  - Extracorporeal life support (ECLS) is a widely used lifesaving technology.
      Whether ECLS results in immune dysregulation is unclear. This study's aim was to
      examine whether ECLS affected innate immune response. All patients placed on ECLS
      were eligible. Blood was obtained before, during, and after ECLS. Function of the
      innate immune system was measured by ex vivo lipopolysaccharide (LPS)-induced
      tumor necrosis factor-alpha (TNF-alpha) and plasma cytokine levels (interleukin
      [IL]-6, IL-8, IL-10, and TNF-alpha). Immunoparalysis was defined as ex vivo TNF
      alpha levels less than 200 pg/ml. Nineteen patients were enrolled with twelve <18
      years old. Median ECLS duration was 10 days (range: 3-108); nine patients died.
      After stratifying the cohort by the presence of immunoparalysis before ECLS,
      those immunoparalyzed showed increased response to LPS on days 1 and 3 (p =
      0.016). Those without pre-ECLS immunoparalysis showed a transient decrease in
      response on day 3 (p = 0.008). Plasma IL-10 levels were elevated in those with
      pre-ECLS immunoparalysis and dropped significantly by day 1 (p = 0.031). The
      number treated with steroids was similar in the two groups. In conclusion,
      patients with immunoparalysis before ECLS showed a gradual increase in immune
      function during ECLS, whereas those without immunoparalysis had a transient
      decrease in responsiveness on day 3.

PMID- 29324514
TI  - Anticoagulant Bridge Comparison in Mechanical Circulatory Support Patients.
AB  - Maintaining mechanical circulatory support (MCS) device patients in a specified
      therapeutic range for anticoagulation remains challenging. Subtherapeutic
      international normalized ratios (INRs) occur frequently while on warfarin
      therapy. An effective anticoagulant bridge strategy may improve the care of these
      patients. This retrospective review of MCS patients with subtherapeutic INRs
      compared an intravenous unfractionated heparin (UFH) strategy with a subcutaneous
      enoxaparin or fondaparinux strategy. Native thromboelastography (n-TEG) was used
      to evaluate anticoagulant effect with coagulation index (CI) as the primary
      outcome measure. Enoxaparin 0.5 mg/kg SC q12hrs or fondaparinux 2.5-5 mg SC daily
      were compared with an initial UFH rate of 5 units/kg/hr and titrated to stated n
      TEG goal range. The anticoagulant groups UFH, enoxaparin, and fondaparinux were
      found to be statistically similar with regard to frequency in n-TEG goal range,
      above range (hypercoagulability), or below range (hypocoagulability). Clinical
      outcomes were similar among groups with three gastrointestinal bleeds in UFH, one
      in enoxaparin, and one in fondaparinux groups. Device thrombosis occurred in one
      UFH patient, while UFH and fondaparinux groups had one ischemic cerebrovascular
      accident event each. These strategies provided comparable n-TEG results and
      clinical outcomes when compared with intravenous UFH. Low-dose enoxaparin or
      fondaparinux may provide an alternative anticoagulant bridging option in MCS
      patients presenting with subtherapeutic INR.

PMID- 29324515
TI  - Acute Cor Pulmonale in Veno-Venous Extracorporeal Membrane Oxygenation: Three
      Case Reports.
AB  - A retrospective review of three patients with acute respiratory distress syndrome
      (ARDS) and normal baseline right ventricular function admitted to the Cardiac
      Surgery Intensive Care Unit whom developed acute cor pulmonale while on veno
      venous extracorporeal membrane oxygenation. These patients were diagnosed with
      ARDS using Berlin Criteria definitions and cannulated with a dual lumen (Avalon)
      cannula. Despite variations in history, presentation, and course, findings of
      acute cor pulmonale were encountered 4 to 6 weeks after extracorporeal membrane
      oxygenation cannulation. The potential mechanisms include thromboembolic burden
      to the pulmonary vasculature, hypoxemia, acidosis, the pathologic progression of
      ARDS, and chronic nonphysiologic flow to the right heart.

PMID- 29324516
TI  - Implants With and Without Laser-Microtextured Collar: A 10-Year Clinical and
      Radiographic Comparative Evaluation.
AB  - INTRODUCTION: This article reports, after at least 10 years of follow-up, the
      comparative data of marginal bone loss (MBL) and periimplant soft tissue
      parameters, around implant with and without laser-microtextured (L) collar
      surface, previously reported at 3 years of follow-up. MATERIALS AND METHODS:
      Twenty implants with L collar surface (test) were placed adjacent to 20 control
      implants with machined (M) collar surface in 15 partially edentulous patients,
      who were followed up for at least 10 years as part of a prospective longitudinal
      study. The plaque score, bleeding on probing (BoP) score, and probing depth (PD)
      were recorded at baseline and at each year follow-up examination. Mucosal
      recession (MR), and radiographic MBL were assessed at baseline and after at least
      10 years. RESULTS: Four patients were lost during follow-up, so the number of
      implants that have been followed for at least 10 years was 32 (16 tests and 16
      controls). At the end of the follow-up period, no significant differences were
      found between the study groups regarding the presence of plaque and BoP (P >
      0.05). A statistically significant difference between test and control implant
      was found for mean PD (2.3 +/- 0.7 mm vs 3.8 +/- 0.8), MBL (1.23 +/- 0.21 mm vs
      2.8 +/- 0.9 mm), and mean MR (1.08 +/- 0.4 mm vs 2.46 +/- 0.3 mm). CONCLUSION:
      Results suggest that after at least 10 years of function, implants with laser
      microtexturing (L) collar surface, compared with implants with machined surface,
      lead to lower MBL and PD.

PMID- 29324517
TI  - Long-term care of transplant recipients: de novo neoplasms after liver
      transplantation.
AB  - PURPOSE OF REVIEW: Since the first liver transplantation in the early 1960s,
      there have been significant improvements in the recipients' long-term outcome.
      Patients who have undergone transplantation are exposed to a high risk of
      developing neoplastic disease, not only because of their chronic
      immunosuppression, but also related to physiological aging, lifestyle, chronic
      viral infections, liver disease cause, and carcinogenic immunosuppressants. The
      present review covers the latest and most relevant data on de novo neoplasms
      after liver transplantation, and discusses their implications for clinical
      practice. RECENT FINDINGS: Given the impact of de novo neoplasms, in terms of
      morbidity and mortality, transplant teams must be prepared to diagnose and treat
      these conditions promptly. Dedicated cancer screening protocols are warranted.
      Although surveillance strategies are based on data concerning the general
      population, they should be customized in the light of each transplant recipient's
      risk factors. The resulting risk stratification is crucially important to the
      design of early intervention programs, and for addressing the modulation of
      individualized immunosuppressive regimens. SUMMARY: De novo malignancies are a
      significant issue for the liver transplant population, but targeted screening
      programs have shown that survival rates similar to those of nonimmunosuppressed
      patients can be achieved. New oncological surveillance strategies covering the
      prophylaxis, monitoring, and treatment of de novo neoplasms should take high
      priority in clinical research.

PMID- 29324518
TI  - The dawn of liver perfusion machines.
AB  - PURPOSE OF REVIEW: Despite high demand, a severe shortage of suitable allografts
      limits the use of liver transplantation for the treatment of end-stage liver
      disease. The transplant community is turning to the utilization of high-risk
      grafts to fill the void. This review summarizes the reemergence of ex-vivo
      machine perfusion for liver graft preservation, including results of recent
      clinical trials and its specific role for reconditioning DCD, steatotic and
      elderly grafts. RECENT FINDINGS: Several phase-1 clinical trials demonstrate the
      safety and feasibility of machine perfusion for liver graft preservation. Machine
      perfusion has several advantages compared with static cold storage and may
      provide superior transplantation outcomes, particularly for marginal grafts.
      Ongoing multicenter trials aim to confirm the results of preclinical and pilot
      studies and establish the clinical utility of ex-vivo liver machine perfusion.
      SUMMARY: Mounting evidence supports the benefits of machine perfusion for
      preservation of liver grafts. Thus, machine perfusion is a promising strategy to
      expand the donor pool by reconditioning and assessing viability of DCD, elderly
      and steatotic grafts during the preservation period. Additionally, machine
      perfusion will serve as a platform to facilitate graft intervention and
      modification to further optimize marginal grafts.

PMID- 29324519
TI  - Cigarette smoking, alcohol drinking, and oral cavity and pharyngeal cancer in the
      Japanese: a population-based cohort study in Japan.
AB  - The effects of cigarette smoking and alcohol drinking on the incidence of oral
      cavity and pharyngeal cancer (OCPC) in the Asian population have been poorly
      understood. To assess the effects of cigarette smoking, alcohol drinking, and
      facial flushing response on incidence of OCPC, a total of 95 525 middle-aged and
      older eligible individuals were followed in a large-scale population-based cohort
      study in Japan from 1990 to 2010. In this study, the person-years of observation
      were 698 006 in men and 846 813 in women, and a total of 222 cases (men=160,
      women=62) of OCPC were newly diagnosed during the study period. A multivariate
      Cox proportional-hazards model was used to assess the incidence risk of OCPC and
      subsites by cigarette smoking and alcohol drinking. The result showed that
      cigarette smoking and regular alcohol drinking were associated significantly with
      the incidence of OCPC in men. Compared with nonsmokers and nondrinkers, current
      male smokers showed a hazard ratio (HR) of 2.37 [95% confidence interval
      (CI)=1.51-3.70] and regular male drinkers showed an HR of 1.82 (95% CI=1.20
      2.76). Cigarette smoking also increased the risk of OCPC among male heavy alcohol
      drinkers (HR=4.05, 95% CI=2.31-7.11). However, there was no significant
      association between facial flushing response and OCPC. In conclusion, cigarette
      smoking and alcohol drinking are independent risk factors for OCPC and its
      subsites in the male Japanese population.

PMID- 29324520
TI  - Vergence responses to face stimuli in young children.
AB  - In line with a possible role of vergence in orienting visual attention, we sought
      to study this eye movement in young children to provide insights on face
      perception. For this purpose, we measured the modulation in the angle of eye
      vergence in a sample of 39 children aged 6-36 months and compared it when
      presenting static human face images versus their scrambled version. We observed
      enhanced vergence responses to faces compared with scrambled images. Our data
      suggest a role of eye vergence in face processing.

PMID- 29324521
TI  - The Efficacy of Transcranical Direct Current Stimulation in Pregabalin Abuse: A
      Case Report.

PMID- 29324522
TI  - How Does Repetitive Transcranial Magnetic Stimulation Influence the Brain in
      Depressive Disorders?: A Review of Neuroimaging Magnetic Resonance Imaging
      Studies.
AB  - OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) is a
      nonpharmacological technique used to stimulate the brain. It is a safe and proven
      alternative tool to treat resistant major depressive disorders (MDDs).
      Neuroimaging studies suggest a wide corticolimbic network is involved in MDDs. We
      researched observable changes in magnetic resonance imaging induced by rTMS to
      clarify the operational mechanism. METHODS: A systematic search of the
      international literature was performed using PubMed and Embase, using papers
      published up to January 1, 2017. The following MESH terms were used: (depression
      or major depressive disorder) and (neuroimaging or MRI) and (rTMS or repetitive
      transcranial magnetic stimulation). We searched the databases using a previously
      defined strategy to identify potentially eligible studies. RESULTS: Both
      structural and functional changes were observed on magnetic resonance imagings
      performed before and after rTMS. Various areas of the brain were impacted when
      rTMS was used. Although the results were very heterogeneous, a pattern that
      involved the anterior cingulate cortex and the prefrontal cortex emerged. These
      are known to be regions of interest in MDDs. However, the various parameters used
      in rTMS make any generalization difficult. CONCLUSIONS: Repetitive transcranial
      magnetic stimulation helps to treat MDDs with good efficacy. Its effect on the
      brain, as observed in several neuroimaging studies, seems to impact on the
      structural and functional features of several networks and structures involved in
      major depressive disorders.

PMID- 29324523
TI  - Towards International Standards: East Meets West.

PMID- 29324524
TI  - ECT and Pronounced Impairment in Spatial Cognition: The Fallacy of Drawing
      Conclusions From a Single Case.
AB  - INTRODUCTION: Electroconvulsive therapy (ECT) is associated with memory deficits
      on neuropsychological assessment. The association of ECT with nonmemory cognitive
      deficits has been poorly studied. METHODS: We present a 40-year-old woman who
      showed a bizarre form of spatial cognition impairment on a subtest of the Tactual
      Performance Test (TPT) after recovering from depression with 6 alternate day,
      thrice-weekly, inpatient ECT treatments. This woman was part of a naturalistic,
      nonblind study that examined nonmemory cognitive deficits in antidepressant
      treated depressed patients who did and did not receive ECT. RESULTS: The
      impairment was in the form of bizarrely drawn reproductions of differently shaped
      wooden blocks that had been presented to the patient when she was blindfolded.
      The impairment was still evident when she was retested (3 hours later) under
      substantially simplified conditions but was much attenuated approximately 2.5
      weeks later. CONCLUSIONS: On the surface, it seems that ECT had induced severe
      impairment in spatial cognition and that the impairment showed the familiar
      pattern of attenuation with the passage of time. However, another recovered
      patient in the study, who did not receive ECT, also showed substantial spatial
      deficits on the same subtest of the TPT, and the attenuation of the deficits
      across time in the ECT-treated patient was probably a result of repeated exposure
      to the task. We suggest that not all patients who seem to experience spectacular
      cognitive impairment after ECT have deficits that are attributable to ECT.

PMID- 29324525
TI  - Pharmacy Students' Preparedness to Communicate With Mental Health Disorders
      Patients.
AB  - The aim of this project was to explore whether fourth-year pharmacy students in
      England are prepared to communicate with mental health patients. Mental health
      problems are rising in the United Kingdom, affecting around one in four people. A
      questionnaire-based study measured the knowledge about and attitude toward mental
      health problems. Participants were fourth-year pharmacy students from two west
      midlands universities. More males than females correctly answered the "attitude
      towards mental health" questions. However, overall, only 45.5% of students
      answered the "attitude towards mental health problems" questions correctly. Males
      demonstrated a better level of knowledge than females, with 33% overall answering
      6 or more questions of the 13 knowledge questions correctly. Sixty-five percent
      of participants scored under 50%. The highest total score was 81%, and the lowest
      was 19%, three people did not answer any questions. In conclusion, a gap in
      knowledge was identified within the fourth-year pharmacy student cohort, and more
      intervention will be required to improve knowledge and attitudes such as the
      Mental Health First Aid courses.

PMID- 29324526
TI  - Do Professional Society Advocacy Campaigns Have an Impact on Pediatric
      Orthopaedic Injuries?
AB  - PURPOSE: The American Academy of Orthopaedic Surgeons (AAOS) and the American
      Academy of Pediatrics (AAP) both advocate for childhood injury prevention by
      publishing recommendations to orthopaedic surgeons, pediatricians, and the
      public. Popular topics of advocacy campaigns have included trampolines, all
      terrain vehicles (ATVs), and lawnmowers. The purpose of this study was to
      investigate the temporal relationship between AAOS/AAP advocacy and pediatric
      orthopaedic injury rates, using these topics as examples. We hypothesized that
      pediatric orthopaedic injury rates decline in years, following related AAOS/AAP
      recommendations. METHODS: A retrospective review of fractures associated with
      trampolines, lawnmowers, and ATVs among patients aged 2 to 18 years from 1991 to
      2014 was performed using the National Electronic Injury Surveillance System
      (NEISS). Fracture rates and percent changes year-to-year were calculated. A
      timeline of AAOS and AAP advocacy statements published on the products was
      created. RESULTS: Trampoline-related fractures rose 14% yearly from 1991 to 1999,
      reached a plateau from 1999 to 2003, corresponding with a 1999 AAP statement.
      Injury rates dropped 4.3% from 2006 to 2010 after 2005 and 2006 statements, and
      reached another plateau thereafter, as 2010 and 2012 statements were published.
      ATV-related fractures rose 14% yearly between 1997 and 2002, then dropped 15%
      from 2007 to 2010 following yearly AAP or AAOS statements from 2004 to 2007. From
      2010 to 2014, the injury rate held constant during which time 2010, 2013, and
      2014 statements were published. Lawnmower injury rates did not fall despite
      statements in 1998 and 2001 and a poster campaign in 2001. A 25% drop from 2007
      to 2008 coincided with an AAOS statement in 2008. Fracture rates further dropped
      31% from 2009 to 2011 and 21% from 2012 to 2014, amidst 2012 and 2014 statements.
      For ATV-related and lawnmower-related injuries, more male individuals were
      affected than female individuals, and for ATVs alone, injury rates increased with
      age. CONCLUSIONS: Although AAOS/AAP statements did not universally coincide with
      dropping fracture rates, statements often were associated with substantial
      decreases in following years. This is likely because injury prevention messages
      are dispersed from providers to the public over time and outcomes depend on
      highly variable patient behaviors. LEVEL OF EVIDENCE: Level V-systematic review
      of descriptive data.

PMID- 29324528
TI  - Titanium Elastic Nailing has Superior Value to Plate Fixation of Midshaft Femur
      Fractures in Children 5 to 11 Years.
AB  - BACKGROUND: American Academy of Orthopaedic Surgeons (AAOS) Clinical Practice
      Guidelines for pediatric femoral shaft fractures indicate titanium elastic nails
      (TENs) for children 5 to 11 years old. Growing evidence suggests these fractures
      may also be treated with open or submuscular plating. The purpose of this study
      was to compare estimated blood loss (EBL), operative time, fluoroscopy time,
      cost, and subjective and objective pain scores between TENs and plating
      techniques used in 5- to 11-year-old children with midshaft femur fractures based
      on length stability. We hypothesized that EBL, operative time, and fluoroscopy
      time would be greater and pain would be lower with plate fixation. METHODS: We
      retrospectively identified all pediatric midshaft femur fractures treated with
      TENs, submuscular plating, or open plating between 2004 and 2014. Demographic,
      injury, and surgical data were obtained for analysis. Cost data were obtained
      from Synthes Inc. Outcomes were determined using the TEN outcome scoring system.
      Variables were compared between the 3 fixation methods using paired t tests or
      Fisher exact test as appropriate. Cost data were compared with Mann-Whitney
      nonparametric test. RESULTS: There were 65 midshaft femur fractures in 63
      patients included. TENs accounted for 77% and plating 23%. There were no
      statistical differences in injury severity score, length of stay, length unstable
      fractures, open fractures, fluoroscopy time, or pain. However, there was a
      significantly greater operative time (P=0.007) and a notably greater EBL
      (P=0.057) for the plating technique compared with TENs. Patient outcomes were
      found to be equivalent. Implant cost was not significantly different although
      increased surgical costs were seen in plating (P=0.0007). CONCLUSIONS: This study
      supports the use of TENs or plating for midshaft femur fractures in children 5 to
      11 years old, regardless of length stability. The use of plates resulted in
      higher EBL, longer operative time, increased cost, and equivalent pain compared
      with TENs. To our knowledge, this study represents the first direct comparison of
      the common fixation methods specifically for midshaft femur fractures and favors
      the use of TENs. LEVEL OF EVIDENCE: Level III.

PMID- 29324527
TI  - Distal Femoral Valgus and Recurrent Traumatic Patellar Instability: Is an
      Isolated Varus Producing Distal Femoral Osteotomy a Treatment Option?
AB  - BACKGROUND: Genu valgum, a risk factor for recurrent patellofemoral instability,
      can be addressed with a varus producing distal femoral osteotomy (DFO). The
      purpose of this study is to report 3-year clinical and radiographic outcomes on a
      series of skeletally mature adolescents with traumatic patellofemoral instability
      and genu valgum who underwent a varus producing DFO. METHODS: Consecutive
      patients (n=11) who underwent an isolated DFO for recurrent traumatic patellar
      instability over a 4-year study period (2009 to 2012) were reviewed. All patients
      were below 19 years of age, skeletally mature, had >=2 patellar dislocations,
      genu valgum (>= zone II mechanical axis) and failed nonoperative treatment.
      Exclusion criteria included less than three-year follow-up, congenital or
      habitual patellar instability, osteotomy indicated for pathology other than
      patellar instability, or biplanar osteotomies. Demographic, clinical, and
      radiographic data were retrospectively analyzed. Recurrence of instability and
      outcome measures (Kujala and Tegner Activity Scale) were collected at final
      followed-up prospectively. RESULTS: Ten of 11 patients (average age, 16 y; range,
      14 to 18 y; 4 male individuals: 7 female individuals) with an average follow-up
      of 4.25 years (range, 3.2 to 6.0 y) met inclusion criteria. The average body mass
      index (BMI) of all patients was 31.3 (range, 19.7 to 46.8) with 91% considered
      overweight (BMI>25) and 55% obese (BMI>30). The average preoperative lateral
      distal femoral angle was 75.4 degrees with an average correction of 10.4 degrees
      (range, 7 to 12 degrees) (P<0.001). Mean patellar height ratios were reduced;
      with Caton-Deschamps Index significantly reduced to 1.08 (range, 0.86 to 1.30)
      (P<0.005). The average postoperative Kujala score was 83.6 (range, 49 to 99) with
      7 subjects (70%) reporting good to excellent function (Kujala > 80) and 8 (80%)
      having no further episodes of instability. The mean postoperative Tegner activity
      score was 5.5 (range, 3 to 7). CONCLUSIONS: A distal femoral varus producing
      osteotomy may change radiographic parameters associated with patellar instability
      and improve clinical outcomes by reducing symptomatic patellofemoral instability
      in this patient population. LEVEL OF EVIDENCE: Level IV.

PMID- 29324529
TI  - Inappropriately Timed Pediatric Orthopaedic Referrals From the Emergency
      Department Result in Unnecessary Appointments and Financial Burden for Patients.
AB  - BACKGROUND: Musculoskeletal injuries are among the most common reasons for
      emergency department (ED) visits in the pediatric population. Many such injuries
      can be managed with a single follow-up outpatient visit. However, untimely (ie,
      premature) referrals by emergency physicians to orthopaedic surgeons are common
      and may inadvertently create need for a second visit, generating unnecessary
      expenditures. We sought to elucidate the cost of premature musculoskeletal follow
      up visits to the patients, families, and the health care system. METHODS: We
      performed a retrospective review of pediatric patients with acute musculoskeletal
      injuries referred from our ED (without a formal orthopaedic consult) to our
      outpatient clinic. Patients were retrospectively reviewed in a consecutive
      fashion. The appropriateness of the recommended follow-up time interval was
      determined for each patient, and the direct and indirect cost of the
      inappropriate services were calculated utilizing a combination of traditional
      cost accounting techniques and time-driven activity-based costing. The
      characteristics of patients with appropriate and untimely follow-up referrals
      were compared. RESULTS: Two hundred consecutive referrals from the ED were
      reviewed. Overall, 96.5% of the follow-up visits recommended by the ED were
      premature, which led 106 (53%) patients to require a second visit to complete
      their clinical care. Patients who required a second visit were significantly
      younger (P=0.005), more likely to be male (P=0.042), more likely to have a
      fracture (P<0.001), and less likely to have a sprain (P<0.001) or
      dislocation/subluxation (P<0.001). Over 40% of second visits were accounted for
      by 3 diagnoses (distal radius buckle fractures, nondisplaced Salter-Harris 1
      fractures of the ankle, and buckle fractures of the finger). Across the whole
      cohort, the total financial impact of untimely visits was $36,265.78,
      representing an average cost of $342.93 per patient. CONCLUSIONS: Untimely
      referrals for follow-up of acute pediatric musculoskeletal conditions are very
      common and represent a significant financial burden to patients, families, and
      the health care system. Over 40% of unnecessary visits resulted from just 3
      diagnoses. Improved orthopaedic follow-up guidelines, particularly for these
      readily recognizable conditions, and feedback to referring providers may reduce
      poorly timed clinic visits and decrease costs in the treatment of common
      orthopaedic injuries in pediatric patients. LEVEL OF EVIDENCE: Level III.

PMID- 29324530
TI  - Early Results of Single-plug Autologous Osteochondral Grafting for
      Osteochondritis Dissecans of the Capitellum in Adolescents.
AB  - BACKGROUND: Osteochondral autologous transplantation surgery (OATS) has been
      advocated for unstable osetochondritis dissecans (OCD) lesions of the adolescent
      capitellum, though limited information is available regarding clinical and
      radiographic results in North American patients. We hypothesize that single-plug
      OATS is safe and effective in alleviating pain and restoring function in unstable
      OCD. METHODS: Twenty-eight patients with unstable OCD treated with single-plug
      OATS were evaluated. Mean age at surgery was 14.2 years; there were 14 males.
      Etiology of OCD was presumed to be sports participation, including baseball (n=5)
      and gymnastics (n=11). Indications for surgery included unstable, deep OCD
      lesions; 2 lesions were uncontained, and 3 patients (11%) had OATS after failed
      prior surgery. OATS was performed by an anconeus muscle-splitting approach; donor
      grafts were harvested from the lateral femoral condyle by small arthrotomy.
      Functional outcomes were quantified using the Timmerman instrument. Median
      clinical and radiographic follow-up was 6.3 months (range, 5.0 to 27.0 mo) and
      5.7 months (range, 5.0 to 26.7 mo), respectively. Furthermore, all patients
      returned functional questionnaires at a median of 9 months postoperatively
      (range, 5 to 27 mo). RESULTS: Of the 26 patients who reported preoperative
      tenderness, 19 (73%) patients had no tenderness at most recent clinical follow-up
      (P=0.02). Of 18 patients with restricted elbow motion preoperatively, 13 had
      achieved full range of motion (P=0.10). Both elbow flexion and extension improved
      significantly [flexion: median change (interquartile range)=10 degrees (0 to 10
      degrees), P=0.009; extension: 0 degree (-5 to 0 degrees), P <0.001). On
      postoperative magnetic resonance imaging, 86% (P<0.001) of elbows had restoration
      of articular congruity and 93% had complete graft incorporation. Objective
      [median change (interquartile range)=5 degrees (0 to 15 degrees)], subjective [25
      degrees (15 to 40 degrees)], and overall [35 degrees (15 to 45 degrees)]
      Timmerman scores improved significantly (P=0.001, <0.001, and <0.001,
      respectively). Of the 13 patients with >6 months follow-up, 9 patients (69%) had
      returned to their primary sport (P=0.27) and 100% had returned to general sports
      participation. There were no postoperative complications. At final follow-up, all
      donor knees were asymptomatic with full motion and strength. CONCLUSION: Single
      plug OATS is safe and effective in improving pain and elbow function in
      adolescents with unstable OCD, with high return to sports rates and little donor
      site morbidity. LEVEL OF EVIDENCE: Level IV-case series.

PMID- 29324531
TI  - Response to a Letter to the Editor.

PMID- 29324532
TI  - Low Expression of Protocadherin-8 Promotes the Progression of Ovarian Cancer.
AB  - OBJECTIVE: Ovarian cancer (OC) is the second most lethal gynecological cancer
      among women throughout the world. Protocadherin-8 (PCDH8) could function as a
      candidate tumor suppressor. However, the link between PCDH8 and OC development is
      poorly understood. MATERIALS AND METHODS: A total of 68 OC patients were
      retrospectively enrolled. Clinical information was collected and cancer tissues
      were used for tissue microarray. The PCDH8 expression was determined on tissue
      microarray by immunohistochemical staining, and PCDH8 protein was detected in
      cancer tissues and adjacent tissue by western blotting. Human OC cell lines (SKOV
      3 and OVCAR-3) were used to assess the effects of PCDH8 overexpression by western
      blot and real-time PCR analysis. 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide cell proliferation assay, wound healing migration
      assay, colony formation assay and invasion assays were performed to assess the
      influence of PCDH8 on cell function. Cells with Luc-nonspecific Lentiviral or Luc
      Lentiviral with PCDH8 gene were subcutaneously injected into nude mice to observe
      the effect of PCDH8 gene on tumor growth. Bioluminescence imaging was used to
      observe tumor volume. RESULTS: We found a low expression of PCDH8 in OC tissues
      versus the corresponding adjacent tissue. The PCDH8 expression, International
      Federation of Gynecology and Obstetrics stage, metastasis and recurrence were the
      independent prognostic factors for over-all survival by multivariate analyses.
      Furthermore, the patients with recurrence presented a low level of PCDH8 in OC
      tissues, and patients with advanced tumor stage also had a low PCDH8 expression.
      Importantly, the low expression of PCDH8 in OC tissues had a poor prognosis with
      a low overall survival rate. Overexpression of PCDH8 could inhibit OC cell
      growth/proliferation, migration, invasion, and colony formation in vitro. In vivo
      experiments also proved that overexpression of PCDH8 could inhibit OC cell
      growth/proliferation. CONCLUSIONS: Protocadherin-8 might be considered as a
      candidate tumor suppressor and play a crucial role in the progression of OC.

PMID- 29324533
TI  - Multicenter Clinicopathological Study of High-Grade Serous Carcinoma Presenting
      as Primary Peritoneal Carcinoma.
AB  - OBJECTIVE: We conducted a multicenter clinicopathological study to characterize
      patients with high-grade serous carcinoma presenting as primary peritoneal
      carcinoma (clinical PPC). METHODS: At 9 sites in Japan, patients with clinical
      PPC diagnosed according to Gynecologic Oncology Group criteria were enrolled
      retrospectively. The Gynecologic Oncology Group criteria allow for minor ovarian
      involvement by high-grade serous carcinoma. There was no systematic detailed
      histopathological review of the fallopian tubes to determine whether they were
      involved by serous carcinoma. RESULTS: There were 139 patients and 64% were aged
      60 years or older. Median pretreatment serum CA-125 was 1653.5 IU/mL.
      Pretreatment performance status was poor in more than 50%, endometrial cytology
      was positive in 40.3%, and the preoperative clinical diagnosis was correct in
      72.7%. Primary debulking surgery was performed in 36% of patients, whereas 64%
      underwent neoadjuvant chemotherapy (NAC) with interval debulking surgery (IDS).
      The main tumor sites were the upper abdomen (greater omentum), extrapelvic
      peritoneum, mesentery, and diaphragm. Lymph node metastasis was found in 46.8% of
      patients undergoing systematic retroperitoneal node dissection. The optimal
      surgery rate was 32.0% with primary debulking surgery versus 53.9% with NAC and
      IDS (P = 0.0139). The response rate was 82.0% with NAC and 80.6% with
      postoperative chemotherapy. Median progression-free survival was 19.0 months and
      median overall survival was 41.0 months. Multivariate analysis showed that
      prognostic factors for progression-free survival were NAC and residual tumor
      diameter after debulking surgery, whereas the only prognostic factor for overall
      survival was the residual tumor diameter. CONCLUSIONS: This study identified
      various characteristics of clinical PPC. Neoadjuvant chemotherapy with IDS is a
      reasonable treatment strategy, and complete debulking surgery is optimum.

PMID- 29324535
TI  - Evaluating the Role of F-18 Fluorodeoxyglucose Positron Emission
      Tomography/Computed Tomography Scanning in the Staging of Patients With Stage
      IIIB Cervical Carcinoma and the Impact on Treatment Decisions.
AB  - OBJECTIVE: FIGO (International Federation of Gynaecology and Obstetrics) staging
      is currently the most widely used clinical staging system for cervical cancer;
      however, this staging system has many shortcomings. One of these shortcomings is
      that lymph nodal status, specifically the para-aortic lymph nodal status, does
      not get taken into account. It is known that metabolic changes occur before
      changes are seen on anatomical imaging, and it is therefore possible to detect
      metastases earlier with the help of fluorodeoxyglucose (FDG) positron emission
      tomography/computed tomography (PET/CT). We hypothesized that by including an FDG
      PET/CT study as part of the staging investigations in patients with invasive
      cervical cancer, pretreatment staging would improve and management would change
      in a significant proportion of patients. METHODS/MATERIALS: Patients diagnosed
      with FIGO stage IIIB cervical cancer from September 2010 to December 2015
      received an FDG PET/CT study as part of their staging workup. A whole-body FDG
      PET/CT was performed before initiation of treatment, and the results were
      interpreted by experienced nuclear medicine physicians and radiologists. We
      determined the percentage of patients in whom PET/CT changed the stage and/or
      altered management of the patient. RESULTS: There were 95 patients diagnosed with
      stage IIIB cervix cancer during the study period who received an FDG PET/CT as
      part of their staging workup. Eighty-eight patients were included in the final
      sample. Positron emission tomography/CT affected the management of 40% of
      patients, with 19% requiring a change in the radiation field due to
      identification of para-aortic nodal involvement and 21% upstaged to stage IVB.
      CONCLUSIONS: Fluorodeoxyglucose PET/CT is useful in assessing distant disease and
      evaluating nodal involvement in patients with invasive cervical cancer.
      Additional findings on the PET/CT that were missed by conventional imaging and
      clinical examination caused treatment change in a significant proportion of
      patients.

PMID- 29324534
TI  - Reproductive Outcomes After Gestational Trophoblastic Neoplasia. A Comparison
      Between Single-Agent and Multiagent Chemotherapy: Retrospective Analysis From the
      MITO-9 Group.
AB  - OBJECTIVES: Gestational trophoblastic neoplasia affects women of reproductive age
      and is usually treated by chemotherapy. Major concerns related to chemotherapy in
      young women are the possible infertility, risk of early menopause, and
      teratogenic effects on subsequent pregnancies. The study's aim was to analyze
      menstrual and reproductive outcomes of women treated with single-agent versus
      multiagent chemotherapy for gestational trophoblastic neoplasia. METHODS: One
      hundred fifty-one patients were treated. Seventy-six patients older than 45
      years, with a placental site or epithelioid trophoblastic tumor, undergoing
      hysterectomy for patient choice, or undergoing human chorionic gonadotropin
      follow-up at the time of the analysis were excluded. Seventy-five patients were
      divided into subgroups according to International Federation of Gynecology and
      Obstetrics score: patients scoring less than 7, receiving single-agent
      chemotherapy (group A, n = 42); patients scoring 7 or greater, receiving
      combination treatment (group B, n = 33). Patients' outcomes were compared by
      univariate and multivariate analyses. RESULTS: Temporary amenorrhea occurred in
      33% of group A patients and 66.7% of group B (P = 0.01). Premature menopause
      occurred in 3 patients in group B (0% vs 9%, P = 0.02). Ten patients in group B
      underwent salvage hysterectomy. Pregnancy desire did not differ between the 2
      groups (P = 0.555). In group A, 57.1% became pregnant; in group B, 36.4% did (P =
      0.060). Instead, pregnancy rate was 52.2% among high-risk patients not undergoing
      hysterectomy (57.1% vs 52.2%, P = 0.449). There was no difference in miscarriage
      (P = 0.479) and premature birth (P = 0.615) rates. In a multivariate analysis
      that included age, International Federation of Gynecology and Obstetrics score,
      chemotherapy type, use of assisted reproductive technologies, previous
      pregnancies, and pregnancy desire, only age (P = 0.006) and pregnancy desire (P =
      0.002) had a significant impact on the probability to have subsequent
      pregnancies. CONCLUSIONS: Except for the risk of premature ovarian failure, a
      rare adverse effect of combined treatments, both single-agent and multiagent
      chemotherapy can be safely administered to patients with a desire for
      childbearing. High-risk patients have worse reproductive outcomes because they
      undergo hysterectomy more frequently than low-risk patients.

PMID- 29324536
TI  - Added Value of Estrogen Receptor, Progesterone Receptor, and L1 Cell Adhesion
      Molecule Expression to Histology-Based Endometrial Carcinoma Recurrence
      Prediction Models: An ENITEC Collaboration Study.
AB  - OBJECTIVES: Endometrial carcinoma mortality is mainly caused by recurrent
      disease, and various immunohistochemical markers to predict recurrences have been
      studied. Loss of the estrogen receptor (ER) and progesterone receptor (PR) and
      the presence of the L1 cell adhesion molecule (L1CAM) are promising markers, but
      their combined value has not been studied. MATERIALS AND METHODS: Expression of
      ER, PR, and L1CAM was immunohistochemically determined in 293 endometrial
      carcinomas from 11 collaborating European Network for Individualized Treatment of
      Endometrial Cancer centers. Estrogen receptor, PR, or L1CAM staining was
      considered positive or negative when expressed by greater than or equal to 10% or
      less than 10% of the tumor cells, respectively. The association between these
      markers and clinicopathological markers, and their combined value in predicting
      survival were calculated, both in the entire cohort and in a selected groups of
      stage I endometrioid and low-risk stage I endometrioid carcinomas. RESULTS:
      Estrogen receptor and PR were negative in 19% and 28% of the cases, respectively,
      and L1CAM was positive in 18%. All 3 were associated with advanced stage, high
      grade, nonendometrioid histology, lymphovascular space invasion (LVSI), and
      reduced disease-free survival. Only advanced stage, loss of PR, and LVSI were
      associated with reduced disease-free survival in multivariate analysis. A
      prognostic model including these 3 markers was superior to 1 including only the 3
      immunohistochemical markers, which was superior to the traditional model. In both
      the stage I endometrioid and the low-risk stage I endometrioid groups, only loss
      of PR was associated with reduced disease-free survival. CONCLUSIONS: Loss of ER
      and PR, and the presence of L1CAM are associated with high risk characteristics,
      and loss of PR is the strongest predictor of recurrent disease. Although a
      combination of these 3 markers is slightly superior to the traditional
      histological markers, a prognostic model including stage, PR expression, and LVSI
      is the most promising model in the identification of high risk carcinomas. In the
      stage I endometrioid carcinomas, PR immunohistochemistry appears to be of
      additional value in predicting recurrences.

PMID- 29324537
TI  - The FIGO Stage IVA Versus IVB of Ovarian Cancer: Prognostic Value and Predictive
      Value for Neoadjuvant Chemotherapy.
AB  - OBJECTIVE: The revised version of the International Federation of Gynaecology and
      Obstetrics (FIGO) staging system (2014) for epithelial ovarian cancer includes a
      number of changes. One of these is the division of stage IV into 2 subgroups.
      Data on the prognostic and predictive significance of this classification are
      scarce. The effect of neoadjuvant chemotherapy (NACT) versus primary debulking
      surgery (PDS) in relation to the subclassification of FIGO stage IV is also
      unknown. METHODS: We used data of the EORTC 55971 trial, in which 670 patients
      with previous stage IIIC or IV epithelial ovarian cancer were randomly assigned
      to PDS or NACT; 160 patients had previous stage IV. Information on previous FIGO
      staging and presence of pleural effusion with positive cytology were used to
      classify tumors as either stage IVA or IVB. We tested the association between
      stage IVA/IVB and survival to evaluate the prognostic value and interactions
      between stage, treatment, and survival to evaluate the predictive performance.
      RESULTS: Among the 160 participants with previous stage IV disease, 103 (64%)
      were categorized as stage IVA and 57 (36%) as stage IVB tumors. Median overall
      survival was 24 months in FIGO stage IVA and 31 months in stage IVB patients (P =
      0.044). Stage IVB patients treated with NACT had 9 months longer median overall
      survival compared with IVB patients undergoing PDS (P = 0.025), whereas in IVA
      patients, no significant difference was observed (24 vs 26 months, P = 0.48).
      CONCLUSIONS: The reclassification of FIGO stage IV into stage IVA or IVB was not
      prognostic as expected. Compared with stage IVA patients, stage IVB patients have
      a better overall survival and may benefit more from NACT.

PMID- 29324538
TI  - Specific Regions, Rather than the Entire Peritoneal Carcinosis Index, are
      Predictive of Complete Resection and Survival in Advanced Epithelial Ovarian
      Cancer.
AB  - BACKGROUND: Advanced epithelial ovarian cancer (EOC) often involves the
      peritoneum. Because complete resection of tumor and carcinosis is the most
      important prognostic factor, the peritoneal carcinosis index (PCI) has been
      evaluated in EOC. We hypothesize that specific PCI regions comprising the small
      intestine with mesentery (regions 9-12) and the hepatoduodenal ligament (region
      2) are more predictive of complete resection (R = 0) and survival than the entire
      PCI. MATERIALS AND METHODS: We analyzed prospectively collected nationwide data
      from 507 patients with International Federation of Gynecology and Obstetrics
      stage IIIB to IVB EOC who underwent primary surgery with complete cytoreductive
      intent. The PCI as a predictor of incomplete resection (R > 0) was evaluated with
      logistic regression and receiver operating caracteristic curves. Survival
      analysis was performed with Kaplan-Meier curves and Cox regression. RESULTS:
      Median (range) PCI was 10 (0-33) in R = 0 patients and 24 (1-39) in R > 0
      patients; P < 0.0001. The PCI of regions 9 to 12 (odds ratio [OR]:1.38 (1.29
      1.47; 95% confidence interval [CI]) and 2 + 9 to 12 (OR: 1.31 [1.24-1.38; 95%
      CI]) were more predictive of residual tumor than the entire PCI (OR: 1.10 [1.08
      1.12; 95% CI]). Similarly, in receiver operating characteristic curve analyses of
      R greater than 0 versus R = 0, the area under the curve was higher in regions 9
      to 12 (78%) and regions 2 + 9 to 12 (79%) than for the total PCI (75%).Median
      overall survival was 56.8 months (48.3-65.4; 95% CI) after R = 0 and 26.7 months
      (21.4-32.0; 95% CI) after R greater than 0 (P < 0.0001). Overall survival was
      53.8 months for patients with PCI less than median (14) versus 25.7 in patients
      with PCI greater than median.The PCI in regions 9 to 12 (hazard ratio [HR]: 1.10
      [1.07-1.13; 95% CI]) and 2 + 9 to 12 (HR: 1.08 [1.06-1.11; 95% CI]) was
      associated with a poorer prognosis than the entire PCI (HR: 1.03 [1.02-1.04; 95%
      CI]). CONCLUSIONS: Selected PCI regions corresponding to the small intestine and
      hepatoduodenal ligament are more predictive of complete resection and survival
      than the entire PCI. This confirms that in the majority of the cases, an early
      intraoperative examination of those selected PCI regions - and not the entire PCI
      - will reveal whether R = 0 is achievable.

PMID- 29324539
TI  - Trial of Optimal Personalised Care After Treatment-Gynaecological Cancer (TOPCAT
      G): A Randomized Feasibility Trial.
AB  - OBJECTIVE: This study aimed to evaluate the feasibility of completing a parallel
      group randomized controlled trial to compare usual follow-up care for women who
      have completed treatment of gynecological cancer against a nurse-led telephone
      intervention, known as Optimal Personalised Care After Treatment-Gynaecological.
      METHODS: The unblinded trial aimed to recruit patients who had completed
      treatment of cervical, endometrial, epithelial ovarian, or vulval cancer within
      the previous 3 months at 3 North Wales hospitals. We randomized participants to
      either usual hospital-based follow-up or specialist nurse-led telephone
      education, empowerment, and structured needs assessment follow-up. The primary
      outcomes assessed the feasibility of running a larger trial including patient
      eligibility, recruitment and retention rates, and outcome measure completion.
      Secondary outcomes were generic and health-related quality of life and a patient
      self-report health service use (Client Service Receipt Inventory) data collected
      at 3 time points (baseline, 3 months, and 6 months). RESULTS: Of the 58 women
      screened, 44 were eligible (76%) and 24 (55%) were recruited and randomized
      (12:12 to control and intervention, respectively). One participant was lost to
      follow-up. Recruited participants had a mean (SD) age of 60 (11.2) years and were
      approximately 5 months from their initial diagnosis (mean [SD], 159 [58] days).
      Seventeen (71%) of the participants had an endometrial cancer diagnosis. All
      outcome measure completion rates exceeded 96%. Although not a core feasibility
      objective, analyses of outcome measures indicated positive changes in quality of
      life and well-being within the Optimal Personalised Care After Treatment
      Gynaecological group; exploratory cost consequence analysis indicated that the
      nurse-led intervention had a mean total service use cost of L27 per patient
      (bootstrapped 95% confidence interval, -L290 to L240) lower than did the standard
      care group. CONCLUSION: Eligibility, recruitment, and retention rates as well as
      outcome measure completion showed that the trial is feasible.

PMID- 29324540
TI  - Metastatic Involvement of Lesser Sac in Advanced Epithelial Ovarian Cancer.
AB  - OBJECTIVES: In advanced epithelial ovarian cancer (AOC), lesser sac (LS)
      metastasis particularly to the supragastric LS (SGLS) may be overlooked,
      resulting in unrecognized residual disease. We aimed to identify the frequency,
      distribution, and predictors of LS metastasis using laparoscopic evaluation at
      laparotomy and perioperative surgical complications associated with evaluation
      and resection/ablation. METHODS: Prospective observational study in consecutive
      patients with AOC undergoing laparotomy for primary or interval cytoreductive
      surgery in 2 centers between November 2013 and December 2016. RESULTS: Of 182 AOC
      patients undergoing laparotomy, 150 were eligible for metastasis distribution
      analysis; 96/150 (64%) had LS metastasis with 90/150 (60%) involving the SGLS,
      including lesser omentum (47.3%), floor (42%), upper recess (24.6%), and caudate
      lobe (22.6%), with 62/90 (68.8%) being less than 1 cm in dimension. Of 144
      undergoing cytoreductive surgery, 92 (64%) had LS metastasis, which was
      completely resected/ablated in 77/92 (83.6%).The strongest multivariate
      predictors of LS metastasis were involvement of Morison pouch (P < 0.001) and
      peritoneal cancer index of 17 or greater (P < 0.001). The LS metastasis was
      significantly associated with diaphragmatic surgery (84% vs 54%), cholecystectomy
      (33% vs 2%), splenectomy (50% vs 14%), retroperitoneal nodal metastasis (75% vs
      49%), and surgical complexity score of 8 or higher (75% vs 35%). Morbidity
      related to treatment of LS metastasis was minimal. CONCLUSIONS: Lesser sac
      metastasis and SGLS metastasis are present in almost two thirds of cases of AOC
      and often small in size. Systematic exploration is necessary to detect and treat
      metastases to LS to prevent unrecognized incomplete cytoreduction.

PMID- 29324541
TI  - Intrauterine Manipulator Use During Minimally Invasive Hysterectomy and Risk of
      Lymphovascular Space Invasion in Endometrial Cancer.
AB  - OBJECTIVE: This study aimed to examine an association between intrauterine
      manipulator (IUM) use and frequency of lymphovascular space invasion (LVSI) in
      women with endometrial cancer undergoing minimally invasive hysterectomy.
      METHODS: A retrospective case-control study was conducted among stage I-IV
      endometrial cancer patients who underwent hysterectomy between 2008 and 2015.
      Medical records were reviewed for patient demographics, surgical details, and
      tumor characteristics. Women who underwent total laparoscopic hysterectomy (TLH)
      with IUM use were compared with women who underwent total abdominal hysterectomy
      (TAH). Review of archived medical record for data collection and propensity score
      matching were performed to adjust for background differences between TLH-IUM and
      TAH groups. A systematic literature review with pooled analysis was performed to
      examine frequency of LVSI. RESULTS: There were 687 women who underwent
      hysterectomy for endometrial cancer. Of those, 419 women underwent TLH with IUM
      use and 194 women underwent TAH. The most common type of IUM was VCare (89.5%).
      There was no statistically significant difference in the frequency of LVSI
      between the 2 groups: 15.1% for TLH-IUM vs 19.9% for TAH (P = 0.14). After
      propensity score matching, frequencies of LVSI were similar between the 2 groups:
      21.2% for TLH-IUM vs 19.6% for TAH (P = 0.78). Systematic literature review
      identified 1371 cases of TLH-IUM and 1246 cases of TAH performed for endometrial
      cancer, and frequencies of LVSI were similar between the 2 groups (15.0% vs
      13.6%, P = 0.31). CONCLUSION: Our study suggests that IUM use during TLH for
      endometrial cancer is not associated with increased frequency of LVSI.

PMID- 29324542
TI  - Extramammary Paget Disease of the Vulva: A Case Series Examining Treatment,
      Recurrence, and Malignant Transformation.
AB  - OBJECTIVES: Extramammary Paget disease (EMPD) of the vulva is a rare lesion with
      a high recurrence rate ranging from 12% to 61%. The rate of underlying
      adenocarcinoma varies, but in the largest series was reported at 4%. Given the
      rarity of the disease there is a paucity of data to optimize treatment. This
      study aims to describe the management and recurrence patterns in a tertiary care
      setting and to offer suggestions for management in a modern-day setting. METHODS:
      Patients with pathologically confirmed EMPD treated from 2000 to 2015 were
      retrospectively identified using an IRB approved database. Clinical data were
      abstracted from the electronic medical record. Pathology underwent central
      review. RESULTS: Forty-four patients met criteria and underwent central pathology
      review. Forty-two patients were treated with surgical excision. Alternative
      treatment modalities included Mohs surgery in 3 patients and medical therapy in
      20 patients. The median number of surgical procedures was 1 and the number of
      procedures ranged from 1 to 16. Twenty-five patients (56.8%) had recurrent
      disease with a median of 2 (1-6) recurrences per patient. The median disease-free
      interval was 28.7 months with a median follow up of 45.8 months (1.2-178.9
      months). Three patients (7%) had invasive cancer and 7 patients (16%) were
      diagnosed with a separate malignancy at or following diagnosis of EMPD. Despite
      radical resection, the majority of patients had positive margins and there was no
      significant difference in disease recurrence between simple and radical resection
      (P = 0.69). CONCLUSIONS: Patients with EMPD in this series have a high rate of
      recurrence. Many undergo multi-modal therapy often with multiple providers.
      However, patients experience relatively long disease-free intervals with a low
      rate of associated malignancy. We propose an algorithm for management that
      focuses on symptom control and minimizing morbidity of treatment intervention
      once invasive disease has been excluded.

PMID- 29324543
TI  - Short-term Outcomes and Pregnancy Rate After Laparoscopic Fertility-Sparing
      Surgery for Borderline Ovarian Tumors: A Single-Institute Experience.
AB  - OBJECTIVE: We investigated the short-term outcomes and pregnancy rate after a
      laparoscopic approach to fertility preservation in patients with borderline
      ovarian tumors (BOTs). METHODS: Clinic-pathologic variants of patients with BOTs
      who underwent conservative surgery at the Tianjin Central Hospital of Obstetrics
      and Gynecology between January 2009 and July 2015 were retrospectively analyzed.
      RESULTS: Among 211 patients with BOTs, 74 (35.1%) received conservative surgery
      (44 cases using a laparoscopic approach and 30 cases using a laparotomy
      approach). The mean age of the laparotomy group was significantly younger than
      that of the laparoscopic group (P = 0.024). The maximal longitude of the tumor in
      the laparotomy group was significantly longer than that in the laparoscopic group
      (P < 0.001). The number of incomplete surgery cases in the laparoscopic group was
      significantly greater than that in the laparotomy group (P < 0.001). The 2 groups
      showed no significant differences in gravidity and parity before surgery,
      abnormality of serum tumor makers, tumor lateralities, ascites, histology,
      duration of follow-up, pregnancy rate after surgery, or postoperative recurrence.
      Total recurrent rate was 6.7% (5/74). Two cases in laparotomy group and 3 cases
      in laparoscopic group relapsed respectively. There was no significant difference
      of recurrent rate between the 2 groups. The total pregnant rate was 33.8%
      (25/74). Nine patients (30%) in the laparotomy group and 16 patients (36.4%) in
      the laparoscopic group became pregnant during follow-up respectively. There were
      no significant differences in the postoperative durations of pregnancy, pregnancy
      type, age at pregnancy, tumor lateralities, ascites, or type of pathology between
      2 groups. The pregnancy rate of incomplete surgery cases in laparoscopic group
      was significantly higher than that of laparotomy group (P = 0.011). No recurrence
      occurred among the pregnant cases. CONCLUSIONS: A comprehensive laparoscopic
      surgery was not performed in incomplete surgery patients undergoing complete
      exploration. Good short-term outcomes and pregnancy were observed in patients
      receiving conservative laparoscopic surgery for BOTs, especially in patients
      receiving incomplete conservative laparoscopic surgery.

PMID- 29324544
TI  - Gestational Trophoblastic Disease Electronic Consults: What Do Patients and
      Physicians Want to Know?
AB  - OBJECTIVES: Given the rarity of gestational trophoblastic disease (GTD),
      specialized regional and national centers for GTD have been established. These
      centers serve at least 3 purposes: to improve care for women with GTD, to enhance
      research though collaboration, and to educate other clinicians. This study was
      undertaken to understand the potential GTD knowledge gap by examining both
      patient and physician inquiries received at a specialized GTD center. METHODS:
      All electronic consults received by specialists at our center between March 2016
      and March 2017 were analyzed. Information collected included source of inquiry,
      reason for the consult, type of GTD, and the advice provided. Descriptive
      statistics were used to analyze the major trends. RESULTS: We analyzed 102
      electronic consults. Physicians sent 49 (48%) and patients sent 53 (52%)
      consults. Most e-consults were sent by physicians and patients within the United
      States; however, 11% of the consults were directed from international locations.
      Among physicians, gynecologic oncologists (65%) were the most common specialty to
      consult our institution followed by medical oncologists (18%) and obstetrician
      gynecologists (16%).Most questions from gynecologic (62%) and medical oncologists
      (77%) concerned treatment regimens. This was contrasted by general obstetrician
      gynecologists who more commonly asked about human chorionic gonadotropin
      monitoring (62%). Difficulty with appropriate Federation of Gynecology and
      Obstetrics staging and World Health Organization risk score assignment were
      common themes. Most of the confusion centered on the use of chest computed
      tomography rather than plain chest x-ray for the assessment of lung metastases.
      Unlike physicians, patient e-consults were most concerned with the duration of
      human chorionic gonadotropin monitoring (51%) and timing of future conceptions.
      CONCLUSIONS: Both physicians and patients in the United States and abroad
      frequently use electronic consults to improve their knowledge about GTD
      management and follow-up. Although the type of inquires varied, they highlight
      fundamental gaps in understanding and potential opportunities for formal
      education.

PMID- 29324545
TI  - The Role of Pathological Margin Distance and Prognostic Factors After Primary
      Surgery in Squamous Cell Carcinoma of the Vulva.
AB  - OBJECTIVE: The aim of this study was to determine the impact of clear surgical
      margin distance and other factors associated with the recurrence and survival of
      patients with squamous cell carcinoma of the vulva. METHODS/MATERIALS: A total of
      107 patients operated for vulvar carcinoma from 1996 to 2016 were included in the
      analysis. Patients were divided into subgroups with clear pathological margin of
      2 mm or less, greater than 2 to less than 8 mm, and 8 mm or greater for the
      analysis of the prognostic impact of the clear margin distance. Data were
      analyzed using the Kaplan-Meier method and Cox proportional hazards regression.
      RESULTS: The median age of the patients was 66 years. The median follow-up was 69
      months. The labia majora and/or labia minora were the most common sites of
      involvement. Radical local excision and radical vulvectomy were performed in 96
      and 11 patients, respectively. Thirty-nine patients received adjuvant
      radiotherapy. The overall recurrence rate was 46%. At 231 months, the actuarial
      local recurrence rate was 18.6%. Patients with clear pathological margin of 2 mm
      or less had significantly higher local recurrence risk. Five-year disease-free
      survival was 32.7%. Older age and adjuvant chemotherapy were found as independent
      prognostic factors for disease-free survival. CONCLUSION: Our data suggest that a
      more than 2 mm tumor-free margins is associated with better local control. In
      addition, older age is an independent prognostic factor for survival.

PMID- 29324546
TI  - Applying Precision Medicine to Ovarian Cancer: Proof-of-Principle for a
      "Molecular Second Look".
AB  - OBJECTIVES: The objectives of this study were to assess if targeted investigation
      for tumor-specific mutations by ultradeep DNA sequencing of peritoneal washes of
      ovarian cancer patients after primary surgical debulking and chemotherapy, and
      clinically diagnosed as disease free, provides a more sensitive and specific
      method to assess actual treatment response and tailor future therapy and to
      compare this "molecular second look" with conventional cytology and
      histopathology-based findings. METHODS/MATERIALS: We identified 10 patients with
      advanced-stage, high-grade serous ovarian cancer who had undergone second-look
      laparoscopy and for whom DNA could be isolated from biobanked paired blood,
      primary and recurrent tumor, and second-look peritoneal washes. A targeted 56
      gene cancer-relevant panel was used for next-generation sequencing (average
      coverage, >6500*). Mutations were validated using either digital droplet
      polymerase chain reaction (ddPCR) or Sanger sequencing. RESULTS: A total of 25
      tumor-specific mutations were identified (median, 2/patient; range, 1-8). TP53
      mutations were identified in at least 1 sample from all patients. All 5 pathology
      based second-look positive patients were confirmed positive by molecular second
      look. Genetic analysis revealed that 3 of the 5 pathology-based negative second
      looks were actually positive. In the 2 patients, the second-look mutations were
      present in either the original primary or recurrent tumors. In the third, 2 high
      frequency, novel frameshift mutations in MSH6 and HNF1A were identified.
      CONCLUSIONS: The molecular second look detects tumor-specific evidence of
      residual disease and provides genetic insight into tumor evolution and future
      recurrences beyond standard pathology. In the precision medicine era, detecting
      and genetically characterizing residual disease after standard treatment will be
      invaluable for improving patient outcomes.

PMID- 29324547
TI  - Stereotactic Body Radiation Therapy, Intensity-Modulated Radiation Therapy, and
      Brachytherapy Boost Modalities in Invasive Cervical Cancer: A Study of the
      National Cancer Data Base.
AB  - BACKGROUND AND PURPOSE: Our objective was to determine whether stereotactic body
      radiotherapy (SBRT), intensity-modulated radiation therapy (IMRT), and
      brachytherapy boost techniques have comparable overall survival in treating
      cervical cancer when adjusted for known prognostic factors. MATERIALS AND
      METHODS: We used the National Cancer Database to study women with invasive
      cervical cancer who were treated with radiation between 2004 and 2013. A logistic
      regression model was built to identify factors associated with the receipt of
      SBRT and IMRT. Outcomes were compared using Kaplan-Meier and propensity score
      matching. RESULTS: Of all 15,905 patients, 14,394 (90.5%) received brachytherapy,
      42 (0.8%) received SBRT, and 1468 (9.2%) received IMRT. After propensity score
      matching, there was no significant difference in overall survival (OS) for
      patients who received SBRT boost versus brachytherapy boost (hazard ratio =
      1.477, 95% confidence interval = 0.746-2.926, P = 0.263) but a significant OS
      detriment in patients who received IMRT boost versus brachytherapy boost (hazard
      ratio = 1.455, 95% confidence interval = 1.300-1.628, P < 0.001). CONCLUSIONS: In
      a propensity-matched analysis, those who received SBRT boost had equal OS when
      compared with brachytherapy, but those who received IMRT boost had worse OS when
      compared with brachytherapy.

PMID- 29324548
TI  - One small step in frailty research, a giant leap in evidence based practice.

PMID- 29324549
TI  - Vocational rehabilitation for emergency services personnel: a scoping review
      protocol.
AB  - REVIEW QUESTION: The objective of this scoping review is to examine and map the
      range of vocational rehabilitation available for law enforcement and emergency
      services personnel.More specifically, the scoping review questions are.

PMID- 29324550
TI  - Effectiveness of the Lean process compared to other quality improvement
      initiatives on length of stay and wait times in healthcare organizations: a
      systematic review protocol.
AB  - REVIEW QUESTION: What is the effectiveness of the Lean process compared to other
      quality improvement initiatives on length of stay and wait times in healthcare
      organizations?

PMID- 29324551
TI  - The I-PASS mnemonic and the occurrence of handoff related errors in adult acute
      care hospitals: a systematic review protocol.
AB  - REVIEW QUESTION: What is the effectiveness of the I-PASS mnemonic in reducing
      handoff related errors during inter- or intrahospital transfers for hospitalized
      patients?The objective of this systematic review is to identify the impact of the
      I-PASS mnemonic during hospitalized patient inter- or intrahospital transfers on
      medication errors, transfer delays, treatment delays and mortality.More
      specifically, the objective is to identify the effect that the I-PASS mnemonic
      has on handoff related errors during inter or intrahospital patient transfers by
      comparing rates pre and post I-PASS implementation.

PMID- 29324552
TI  - Enteral nutrition for the intubated adult intensive care unit patient prior to
      general anesthesia: a scoping review protocol.
AB  - REVIEW QUESTION: The objectives of this scoping review are to examine and map
      fasting times for adult intubated intensive care unit (ICU) patients prior to
      general anesthesia and patient outcomes following the cessation of enteral
      nutrition, to examine and conceptually map the evidence, and identify any
      gaps.Specifically, the review questions are.

PMID- 29324553
TI  - Effectiveness of ultrasound-guided peripheral intravenous cannulation in
      pediatric patients aged under three years: a systematic review protocol.
AB  - REVIEW QUESTION: The objective of this systematic review is to identify, evaluate
      and synthesize evidence of effectiveness on ultrasound-guided peripheral
      intravenous cannulation in pediatric patients aged under three years.Specially,
      the review question is: In pediatric patients aged under three years, what is the
      effect of ultrasound-guided peripheral intravenous cannulation on the first
      attempt and on the overall success rate, time to cannulation and number of
      attempts for successful cannulation compared with the traditional blind approach?

PMID- 29324554
TI  - Geriatric Nursing Sensitive Indicators and quality nursing care for the older
      person: a scoping review protocol.
AB  - REVIEW QUESTION: The objective of the scoping review is to locate and describe
      the international literature relating to Nursing Sensitive Indicators (NSIs) and
      their use in evaluating geriatric care. Specifically the review question is: What
      definitions and key concepts of NSIs are identified in the current literature
      that are relevant in evaluating nursing care of the older person?Findings from
      the review will inform future research and health care responses to support the
      provision of quality nursing care to the older person.

PMID- 29324555
TI  - The association between paternal body mass index, pregnancy success and child
      health outcomes: a systematic review protocol.
AB  - REVIEW QUESTION: The objective of this review is to investigate the association
      between paternal body mass index (BMI) (particularly elevated paternal BMI) and
      complications of conception and pregnancy as well as neonatal and childhood
      health.

PMID- 29324556
TI  - Observer variation in the delineation of organs at risk for head and neck
      radiation therapy treatment planning: a systematic review protocol.
AB  - REVIEW QUESTION: The objective of this review is to examine inter- and intra
      observer agreement and reliability in the delineation of head and neck organs at
      risk (OAR) as part of the radiation therapy treatment planning process.More
      specifically, the objectives are to identify.

PMID- 29324557
TI  - Factors influencing participation in fecal occult blood testing to screen for
      colorectal cancer in Australia: a scoping review protocol.
AB  - REVIEW QUESTION: The objective of this scoping review is to examine and map the
      evidence on the range of factors influencing a person's decision to screen or not
      screen for colorectal cancer using a fecal occult blood test (FOBT) in Australia,
      with the view to identifying gaps in the research and informing appropriate
      questions for future systematic reviews.The question of this review is: what
      evidence is available around the barriers and facilitators that influence an
      individual's decision to screen or not screen for colorectal cancer using a fecal
      occult blood test in Australia?

PMID- 29324558
TI  - The impact of outpatient telehealth compared to standard care on emergency room
      visits and hospital admissions in pediatric diabetes patients: a systematic
      review protocol.
AB  - REVIEW QUESTION: What is the effectiveness of outpatient telehealth compared to
      standard care on emergency room and hospital admissions in patients aged 0 to 18
      years with type 1 or type 2 diabetes?

PMID- 29324559
TI  - Nurse experiences of medication administration to people with swallowing
      difficulties living in aged care facilities: a systematic review of qualitative
      evidence.
AB  - OBJECTIVE: To identify nurses' experiences of administering oral medications to
      residents of aged care facilities (ACFs) with swallowing difficulties.
      INTRODUCTION: Administering medicines to older people with swallowing
      difficulties is a challenging task. Nurses frequently modify oral medications
      e.g. by crushing/splitting tablets or opening capsules, to facilitate the
      administration process. These practices are associated with an increased risk of
      medication administration errors. However, the reasons for these practices from
      the nurse's perspective are not well understood. INCLUSION CRITERIA: The review
      investigated studies on the experiences of nurses of any level with the
      responsibility of medication administration in ACFs in terms of problems and
      challenges they encountered when administering oral medicines to aged care
      residents with swallowing difficulties. Aged care facilities providing all levels
      of care were considered for inclusion. Qualitative studies including, but not
      limited to, phenomenology, grounded theory, ethnography and action research
      designs as well as mixed methods studies and text and opinion papers were
      considered. METHODS: A comprehensive database search of PubMed, CINAHL, Embase
      and Scopus was conducted between October and December 2016. MedNar and ProQuest
      Dissertations and Theses were used to search for gray literature. No date
      limitation was applied. The Joanna Briggs Institute Qualitative Assessment and
      Review Instrument critical appraisal tool (JBI-QARI) was used to assess the
      quality of the papers. The JBI-QARI data extraction instrument was used to
      extract qualitative findings. Data synthesis was not applicable in the final
      analysis due to the inclusion of only one article. RESULTS: The initial search
      resulted in 1681 unique titles for screening. A total of 202 abstracts were
      screened, after which a full-text review conducted for 19 articles. After the
      full-text review, only one article was eligible to be included in the final
      report. The included study scored highly in terms of methodological quality. The
      findings highlighted issues around time constraints, complexity of medication
      administration process to residents of ACFs with swallowing difficulties, cost
      and resources for alternative strategies, inefficient information flow and
      communication among healthcare professionals, and nurses' knowledge and training
      needs. CONCLUSION: The limited findings of this systematic review indicate that
      further research is necessary to provide evidence of nurses' experiences with
      regards to administering oral medications to older people with swallowing
      difficulties living in ACFs. A comprehensive understanding of these experiences
      may lead to organizational system changes to support nurses and older people with
      swallowing difficulties in ACFs.

PMID- 29324560
TI  - Contrast media extravasations in patients undergoing computerized tomography
      scanning: a systematic review and meta-analysis of risk factors and
      interventions.
AB  - OBJECTIVE: To identify risk factors and interventions preventing or reducing
      contrast medium extravasation. INTRODUCTION: Computed tomography (CT) is a
      radiological examination essential for the diagnosis and monitoring of many
      diseases. It is often performed with the intravenous (IV) injection of contrast
      agents. Use of these products can result in a significant complication,
      extravasation, which is the accidental leakage of IV material into the
      surrounding tissue. Patients may feel a sharp pain and skin ulceration or
      necrosis may develop. INCLUSION CRITERIA: This review considered studies that
      included patients (adults and children) undergoing a CT with IV administration of
      contrast media. The risk factors considered were patient demographics,
      comorbidities and medication history. This review also investigated any
      strategies related to: contrast agent, injection per se, material used for
      injection, apparatus used, healthcare professionals involved, and patient risk
      assessment performed by the radiology personnel. The comparators were other
      interventions or usual care. This review investigated randomized controlled
      trials and non-randomized controlled trials. When neither of these were
      available, other study designs, such as prospective and retrospective cohort
      studies, case-control studies and case series, were considered for inclusion.
      Primary outcomes considered were: extravasation frequency, volume, severity and
      complications. METHODS: The databases PubMed, CINAHL, Embase, the Cochrane
      Register of Controlled Trials, Web of Science PsycINFO, ProQuest Dissertations
      and Theses A&I, TRIP Database and ClinicalTrials.gov were searched to find both
      published and unpublished studies from 1980 to September 2016. Papers were
      assessed by two independent reviewers for methodological validity using the
      Joanna Briggs Institute System for the Unified Management, Assessment and Review
      of Information (JBI SUMARI). Data were extracted using the standardized data
      extraction tool from JBI SUMARI. In one case, quantitative data from two cohort
      studies were pooled in a statistical meta-analysis. However, generally,
      statistical pooling was not possible due to heterogeneity of the interventions,
      populations of interest or outcomes. Accordingly, the findings have been
      presented in narrative form. RESULTS: Fifteen articles were selected from a total
      of 2151 unique studies identified. Two were randomized controlled trials and 13
      were quasi-experimental and observational studies. The quality of these studies
      was judged to be low to moderate. Some patient characteristics, such as female
      sex and inpatient status, appeared to be risk factors for extravasation.
      Additionally, injection rate, venous access site and catheter dwelling time could
      affect the volume extravasated. Preliminary studies seemed to indicate the
      potential of extravasation detection accessories to identify extravasation and
      reduce the volume extravasated. The other interventions either did not result in
      significant reduction in the frequency/volume of extravasation, or the results
      were mixed across the studies. CONCLUSIONS: The majority of the studies included
      in this review evaluated the outcomes of extravasation frequency and volume.
      Given the quality of the primary studies, this systematic review identified only
      potential risk factors and interventions. It further highlighted the research gap
      in this area and the importance of conducting trials with solid methodological
      designs.

PMID- 29324561
TI  - Nursing Minimum Data Sets for documenting nutritional care for adults in primary
      healthcare: a scoping review.
AB  - OBJECTIVE: To identify all published nutritional screening instruments that have
      been validated in the adult population in primary healthcare settings and to
      report on their psychometric validity. INTRODUCTION: Within health care, there is
      an urgent need for the systematic collection of nursing care data in order to
      make visible what nurses do and to facilitate comparison, quality assurance,
      management, research and funding of nursing care. To be effective, nursing
      records should accurately and comprehensively document all required information
      to support safe and high quality care of patients. However, this process of
      documentation has been criticized from many perspectives as being highly
      inadequate. A Nursing Minimum Data Set within the nutritional area in primary
      health care could therefore be beneficial in order to support nurses in their
      daily documentation and observation of patients. INCLUSION CRITERIA: The review
      considered studies that included adults aged over 18 years of any gender,
      culture, diagnosis and ethnicity, as well as nutritional experts, patients and
      their relatives. The concepts of interest were: the nature and content of any
      nutritional screening tools validated (regardless of the type of validation) in
      the adult population in primary healthcare; and the views and opinions of
      eligible participants regarding the appropriateness of nutritional assessment
      were the concept of interest. Studies included must have been conducted in
      primary healthcare settings, both within home care and nursing home facilities.
      METHODS: This scoping review used a two-step approach as a preliminary step to
      the subsequent development of a Nursing Minimum Data Set within the nutritional
      area in primary healthcare: i) a systematic literature search of existing
      nutritional screening tools validated in primary health care; and ii) a
      systematic literature search on nutritional experts opinions on the assessment of
      nutritional nursing care of adults in primary healthcare as well as the views of
      patients and their relatives. Multiple databases (PubMed, CINAHL, Embase, Scopus,
      Swemed+, MedNar, CDC, MEDION, Health Technology Assessment Database, TRIP
      database, NTIS, ProQuest Dissertations and Theses, Google Scholar, Current
      Contents) were searched from their inception to September 2016. RESULTS: The
      results from the studies were extracted using pre-developed extraction tools to
      all three questions, and have been presented narratively and by using figures to
      support the text. Twenty-nine nutritional screening tools that were validated
      within a primary care setting, and two documents on consensus statements
      regarding expert opinion were identified. No studies on the patients or relatives
      views were identified. CONCLUSIONS: The nutritional screening instruments have
      solely been validated in an over-55 population. Construct validity was the type
      of validation most frequently used in the validation process covering a total of
      25 of the 29 tools. Two studies were identified in relation to the third review
      question. These two documents are both consensus statement documents developed by
      experts within the geriatric and nutritional care field. Overall, experts find it
      appropriate to: i) conduct a comprehensive geriatric assessment, ii) use a
      validated nutritional screening instrument, and iii) conduct a history and
      clinical diagnosis, physical examination and dietary assessment when assessing
      primarily the elderly's nutritional status in primary health care.

PMID- 29324563
TI  - Nutritional screening, assessment and implementation strategies for adults in an
      Australian acute tertiary hospital: a best practice implementation report.
AB  - OBJECTIVE: The project aimed to improve the effectiveness of nutritional
      screening and assessment practices through clinical audits and the implementation
      of evidence-based practice recommendations. INTRODUCTION: In the absence of
      optimal nutrition, health may decline and potentially manifest as adverse health
      outcomes. In a hospitalized person, poor nutrition may adversely impact on the
      person's outcome. If the nutritional status can be ascertained, nutritional needs
      can be addressed and potential risks minimized.The overall purpose of this
      project was to review and monitor staff compliance with nutritional screening and
      assessment best practice recommendations ensuring there is timely, relevant and
      structured nutritional therapeutic practices that support safe, compassionate and
      person-centered care in adults in a tertiary hospital in South Western Sydney,
      Australia, in the acute care setting. METHODS: A baseline retrospective chart
      audit was conducted and measured against 10 best practice criteria in relation to
      nutritional screening and assessment practices. This was followed by a
      facilitated multidisciplinary focus group to identify targeted strategies,
      implementation of targeted strategies, and a post strategy implementation chart
      audit.The project utilized the Joanna Briggs Institute Practical Application of
      Clinical Evidence System (JBI PACES) and Getting Research into Practice (GRIP)
      tool, including evidence from other available supporting literature, for
      promoting change in healthcare practice. RESULTS: The baseline audit revealed
      deficits between current practice and best practice across the 10 criteria.
      Barriers for implementation of nutritional screening and assessment best practice
      criteria were identified by the focus group and an education strategy was
      implemented. There were improved outcomes across all best practice criteria in
      the follow-up audit. CONCLUSIONS: The baseline audit revealed gaps between
      current practice and best practice. Through the implementation of a targeted
      education program and resource package, outcomes improved in the follow up audit.
      The findings indicated that engagement from multidisciplinary team members and
      consumers was effective in developing tailored education that improved knowledge
      of best practice. This was demonstrated by an increase in the percentage of
      compliance across the 10 criteria, although leaving room for more improvement. A
      policy has been developed for implementation and future audits are planned to
      measure whether improved practices have been sustained.

PMID- 29324562
TI  - Effectiveness of interventions to prevent pre-frailty and frailty progression in
      older adults: a systematic review.
AB  - OBJECTIVE: To summarize the best available evidence regarding the effectiveness
      of interventions for preventing frailty progression in older adults.
      INTRODUCTION: Frailty is an age-related state of decreased physiological reserves
      characterized by an increased risk of poor clinical outcomes. Evidence supporting
      the malleability of frailty, its prevention and treatment, has been presented.
      INCLUSION CRITERIA: The review considered studies on older adults aged 65 and
      over, explicitly identified as pre-frail or frail, who had been undergoing
      interventions focusing on the prevention of frailty progression. Participants
      selected on the basis of specific illness or with a terminal diagnosis were
      excluded. The comparator was usual care, alternative therapeutic interventions or
      no intervention. The primary outcome was frailty. Secondary outcomes included:
      (i) cognition, quality of life, activities of daily living, caregiver burden,
      functional capacity, depression and other mental health-related outcomes, self
      perceived health and social engagement; (ii) drugs and prescriptions, analytical
      parameters, adverse outcomes and comorbidities; (iii) costs, and/or costs
      relative to benefits and/or savings associated with implementing the
      interventions for frailty. Experimental study designs, cost effectiveness, cost
      benefit, cost minimization and cost utility studies were considered for
      inclusion. METHODS: Databases for published and unpublished studies, available in
      English, Portuguese, Spanish, Italian and Dutch, from January 2001 to November
      2015, were searched. Critical appraisal was conducted using standardized
      instruments from the Joanna Briggs Institute. Data was extracted using the
      standardized tools designed for quantitative and economic studies. Data was
      presented in a narrative form due to the heterogeneity of included studies.
      RESULTS: Twenty-one studies, all randomized controlled trials, with a total of
      5275 older adults and describing 33 interventions, met the criteria for
      inclusion. Economic analyses were conducted in two studies. Physical exercise
      programs were shown to be generally effective for reducing or postponing frailty
      but only when conducted in groups. Favorable effects on frailty indicators were
      also observed after the interventions, based on physical exercise with
      supplementation, supplementation alone, cognitive training and combined
      treatment. Group meetings and home visits were not found to be universally
      effective. Lack of efficacy was evidenced for physical exercise performed
      individually or delivered one-to-one, hormone supplementation and problem solving
      therapy. Individually tailored management programs for clinical conditions had
      inconsistent effects on frailty prevalence. Economic studies demonstrated that
      this type of intervention, as compared to usual care, provided better value for
      money, particularly for very frail community-dwelling participants, and had
      favorable effects in some of the frailty-related outcomes in inpatient and
      outpatient management, without increasing costs. CONCLUSIONS: This review found
      mixed results regarding the effectiveness of frailty interventions. However,
      there is clear evidence on the usefulness of such interventions in carefully
      chosen evidence-based circumstances, both for frailty itself and for secondary
      outcomes, supporting clinical investment of resources in frailty intervention.
      Further research is required to reinforce current evidence and examine the impact
      of the initial level of frailty on the benefits of different interventions. There
      is also a need for economic evaluation of frailty interventions.

PMID- 29324564
TI  - Falls assessment and interventions among older patients in two medical and one
      surgical hospital wards in Spain: a best practice implementation project.
AB  - OBJECTIVE: The current project aimed to improve fall prevention and management
      through clinical audits and the implementation of a quality-improvement cycle at
      the local level. INTRODUCTION: Falls are one of the most common adverse events
      reported in hospitals; evidence-based fall prevention interventions aim to reduce
      the number of people who fall. METHODS: A one-year clinical audit was conducted
      using a pre-post implementation audit method, namely the Joanna Briggs
      Institute's (JBI) Practical Application of Clinical Evidence System and the
      getting research into practice audit and feedback tool. Two medical wards and a
      surgical ward in a Spanish hospital participated. The subjects were evaluated at
      baseline and at a follow-up at six months after key strategies had been
      implemented. RESULTS: Compliance rates for the evidence-based criteria were low
      in the baseline audit. Five barriers were identified in relation to fall
      assessment and management and, based on getting research into practice,
      strategies were designed, developed and implemented to overcome these barriers.
      After implementation, most of the fall-risk-assessment criteria showed an overall
      improvement, but there was no effect on care plan recording. Awareness of the
      assessment and management of fall risks were increased among professionals and
      patients on all three study wards. CONCLUSIONS: The current project may improve
      compliance with regard to promoting evidence-based fall prevention and management
      interventions. Further audits are necessary to evaluate any improvements
      achieved, in particular, care plans.

PMID- 29324565
TI  - Assessment of Child Lead Exposure in a Philadelphia Community, 2014.
AB  - INTRODUCTION: Several urban neighborhoods in Philadelphia, Pennsylvania, have a
      history of soil, household lead paint, and potential lead-emitting industry
      contamination. OBJECTIVES: To (1) describe blood lead levels (BLLs) in target
      neighborhoods, (2) identify risk factors and sources of lead exposure, (3)
      describe household environmental lead levels, and (4) compare results with
      existing data. METHODS: A simple, random, cross-sectional sampling strategy was
      used to enroll children 8 years or younger living in selected Philadelphia
      neighborhoods with a history of lead-emitting industry during July 2014.
      Geometric mean of child BLLs and prevalence of BLLs of 5 MUg/dL or more were
      calculated. Linear and logistic regression analyses were used to ascertain risk
      factors for elevated BLLs. RESULTS: Among 104 children tested for blood lead, 13
      (12.4%; 95% confidence interval [CI], 7.5-20.2) had BLLs of 5 MUg/dL or more. The
      geometric mean BLL was 2.0 MUg/dL (95% CI, 1.7-2.3 MUg/dL). Higher geometric mean
      BLLs were significantly associated with front door entryway dust lead content,
      residence built prior to 1900, and a child currently or ever receiving Medicaid.
      Seventy-one percent of households exceeded the screening level for soil, 25% had
      an elevated front door floor dust lead level, 28% had an elevated child play area
      floor dust lead level, and 14% had an elevated interior window dust lead level.
      Children in households with 2 to 3 elevated environmental lead samples were more
      likely to have BLLs of 5 MUg/dL or more. A spatial relationship between household
      proximity to historic lead-emitting facilities and child BLL was not identified.
      CONCLUSION: Entryway floor dust lead levels were strongly associated with blood
      lead levels in participants. Results underscore the importance to make housing
      lead safe by addressing all lead hazards in and around the home. Reduction of
      child lead exposure is crucial, and continued blood lead surveillance, testing,
      and inspection of homes of children with BLLs of 5 MUg/dL or more to identify and
      control lead sources are recommended. Pediatric health care providers can be
      especially vigilant screening Medicaid-eligible/enrolled children and children
      living in very old housing.

PMID- 29324566
TI  - Maintaining a Competent Public Health Workforce: Lessons Learned From Experiences
      With Public Health Accreditation Domain 8 Standards and Measures.
AB  - CONTEXT: Public health accreditation is an ongoing national movement to improve
      the quality of public health departments and the public health system in the
      United States; however, calls have been made for more evidence regarding best
      practices in the accreditation process. OBJECTIVE: The purpose of this work is to
      provide evidence about best practices in the accreditation process, specifically
      within the workforce development domain. It is the first in-depth investigation
      into workforce development using data collected by Public Health Accreditation
      Board (PHAB). DESIGN: Using deidentified accreditation application data from
      PHAB, this study employs a mixed-methods approach to examining practices, lessons
      learned, challenges, and strategies pertaining to workforce development planning
      for Domain 8. SETTING: United States. PARTICIPANTS: US state (n = 19) and local
      health departments (n = 115). MAIN OUTCOME MEASURES: Public Health Accreditation
      Board assessment scores for the workforce measures and the relationship between
      the health department's approach to meeting a PHAB measure criteria and the PHAB
      assessment score. RESULTS: Of the 9 different approaches identified as ways of
      encouraging the development of a sufficient number of qualified public health
      workers (version 1, measure 8.1.1), only 1 approach (local health department
      internship programs with schools of public health; B = 0.25, P < .03) was
      significantly related to higher scores. An opportunity for improvement identified
      for measure 8.2.1 was that plans missing a clear identification of the gap
      between current staff competencies and staff needs were associated with a 0.88
      point decrease in the 4-point score (P < .001). CONCLUSIONS: Findings suggest
      that there are approaches adopted for meeting PHAB domain 8 measures that will
      impact the overall conformance assessment and score of a health department
      pursuing accreditation. There are several opportunities for improvement that
      health departments might consider when planning for accreditation or assessing
      their activities.

PMID- 29324567
TI  - Electronic Health Record Implementation Findings at a Large, Suburban Health and
      Human Services Department.
AB  - OBJECTIVE: Evaluate an electronic health record (EHR) implementation across a
      large public health department to better understand and improve implementation
      effectiveness of EHRs in public health departments. DESIGN: A survey based on
      Consolidated Framework for Implementation Research constructs was administered to
      staff before and after implementation of an EHR. SETTING: Large suburban county
      department of health and human services that provides clinical, behavioral,
      social, and oral health services. PARTICIPANTS: Staff across 4 program areas
      completed the survey prior to EHR implementation (n = 331, June 2014) and 3
      months post-EHR final implementation (n = 229, December 2015). INTERVENTION:
      Electronic health record MAIN OUTCOME MEASURES:: Constructs were validated using
      confirmatory factor analysis and included information strengths and information
      gaps in the current environment; EHR impacts; ease of use; future use intentions;
      usefulness; knowledge of system; and training. Paired t tests and Wilcoxon signed
      rank tests of a matched sample were performed to compare the pre-/postrespondent
      scores. RESULTS: A majority of user perceptions and expectations showed a
      significant (P < .05) decline 3 months postimplementation as compared with the
      baseline with variation by service area and construct. Staff perceived the EHR to
      be less useful and more complex, provide fewer benefits, and reduce information
      access shortly after implementation. CONCLUSIONS: Electronic health records can
      benefit public health practices in many ways; however, public health departments
      will face significant challenges incorporating EHRs, which are typically designed
      for non-public health settings, into the public health workflow. Electronic
      health record implementation recommendations for health departments are provided.
      When implementing an EHR in a public health setting, health departments should
      provide extensive preimplementation training opportunities, including EHR
      training tailored to job roles, competencies, and tasks; assess usability and
      specific capabilities at a more granular level as part of procurement processes
      and consider using contracting language to facilitate usability, patient safety,
      and related evaluations to enhance effectiveness and efficiencies and make
      results public; apply standard terminologies, processes, and data structures
      across different health department service areas using common public health
      terminologies; and craft workforce communication campaigns that balance potential
      expected benefits with realistic expectations.

PMID- 29324568
TI  - Effects of pressure support ventilation on ventilator-induced lung injury in mild
      acute respiratory distress syndrome depend on level of positive end-expiratory
      pressure: A randomised animal study.
AB  - BACKGROUND: Harmful effects of spontaneous breathing have been shown in
      experimental severe acute respiratory distress syndrome (ARDS). However, in the
      clinical setting, spontaneous respiration has been indicated only in mild ARDS.
      To date, no study has compared the effects of spontaneous assisted breathing with
      those of fully controlled mechanical ventilation at different levels of positive
      end-expiratory pressure (PEEP) on lung injury in ARDS. OBJECTIVE: To compare the
      effects of assisted pressure support ventilation (PSV) with pressure-controlled
      ventilation (PCV) on lung function, histology and biological markers at two
      different PEEP levels in mild ARDS in rats. DESIGN: Randomised controlled
      experimental study. SETTING: Basic science laboratory. PARTICIPANTS: Thirty-five
      Wistar rats (weight +/- SD, 310 +/- 19) g received Escherichia coli
      lipopolysaccharide (LPS) intratracheally. After 24 h, the animals were
      anaesthetised and randomly allocated to either PCV (n=14) or PSV (n=14) groups.
      Each group was further assigned to PEEP = 2 cmH2O or PEEP = 5 cmH2O. Tidal volume
      was kept constant (~6 ml kg). Additional nonventilated animals (n=7) were used as
      a control for postmortem analysis. MAIN OUTCOME MEASURES: Ventilatory and
      mechanical parameters, arterial blood gases, diffuse alveolar damage score,
      epithelial integrity measured by E-cadherin tissue expression, and biological
      markers associated with inflammation (IL-6 and cytokine-induced neutrophil
      chemoattractant, CINC-1) and type II epithelial cell damage (surfactant protein
      B) were evaluated. RESULTS: In both PCV and PSV, peak transpulmonary pressure was
      lower, whereas E-cadherin tissue expression, which is related to epithelial
      integrity, was higher at PEEP = 5 cmH2O than at PEEP = 2 cmH2O. In PSV, PEEP = 5
      cmH2O compared with PEEP = 2 cmH2O was associated with significantly reduced
      diffuse alveolar damage score [median (interquartile range), 11 (8.5 to 13.5) vs.
      23 (19 to 26), P = 0.005] and expressions of IL-6 and CINC-1 (P = 0.02 for both),
      whereas surfactant protein-B mRNA expression increased (P = 0.03). These changes
      suggested less type II epithelial cell damage at a PEEP of 5 cmH2O. Peak
      transpulmonary pressure correlated positively with IL-6 [Spearman's rho (rho) =
      0.62, P = 0.0007] and CINC-1 expressions (rho = 0.50, P = 0.01) and negatively
      with E-cadherin expression (rho = -0.67, P = 0.0002). CONCLUSION: During PSV,
      PEEP of 5 cmH2O, but not a PEEP of 2 cmH2O, reduced lung damage and inflammatory
      markers while maintaining epithelial cell integrity.

PMID- 29324569
TI  - Does the Vaginal Flora Modify When a Synthetic Mesh is Used for Genital Prolapse
      Repair in Postmenopausal Women? A Pilot, Randomized Controlled Study.
AB  - OBJECTIVE: The vaginal flora from postmenopausal women with pelvic organ prolapse
      (POP) is different from younger women. We hypothesized that the decision of a
      surgical route using a mesh would modify the vaginal flora. The purpose of this
      study was to analyze the vaginal flora from postmenopausal women that were
      submitted to abdominal sacrocervicopexy or vaginal sacrospinous fixation.
      METHODS: A pilot, randomized controlled study with 50 women aged 55 to 75 years
      (n = 25; abdominal sacrocervicopexy + subtotal hysterectomy; n = 25 vaginal
      sacrospinous fixation + vaginal hysterectomy) was performed. A polyvinylidene
      mesh was used in both arms. The vaginal content analysis was collected before and
      60 days after the surgery. The type of flora, the presence of
      lactobacilli/leukocytes, and the Nugent criteria were analyzed. RESULTS: Most of
      the women were white (80%), with at least 1 comorbidity (69.9%), did not present
      sexual activity (60%), and presented advanced stage 4 POP. Two thirds of women
      presented a type 3 flora, and half of them did not present lactobacilli (48.3%).
      About the Nugent criteria, 51.7% presented normal flora, 46.6% found altered
      flora, and 1.7% had bacterial vaginosis. There were no differences about the type
      of flora (P = 1), number of lactobacilli (P = 0.9187), Nugent criteria (P =
      0.4235), inflammation (P = 0.1018), and bacterial vaginosis (P = 0.64) before and
      after surgery in both groups. CONCLUSIONS: In this pilot study, the use of
      synthetic mesh by vaginal or abdominal route did not affect the vaginal flora in
      postmenopausal women operated on by POP surgery.

PMID- 29324570
TI  - Long-Term Outcomes After Overlapping Sphincteroplasty for Cloacal-Like
      Deformities.
AB  - OBJECTIVE: The aim of this study was to report subjective, long-term outcomes and
      describe patient demographics, presenting symptoms, perioperative management, and
      complications after overlapping sphincteroplasty repair for chronic fourth-degree
      lacerations (cloacal-like deformities). METHODS: In this retrospective study,
      hospital records were reviewed for women who underwent overlapping anal
      sphincteroplasty for a cloacal-like deformity of the perineum at a single
      institution from 1996 to 2013. Details including patient demographics, presenting
      symptoms, perioperative management, and complications were abstracted from the
      medical record. As a follow-up, subjects were contacted by telephone and were
      administered the validated Modified Manchester Health Questionnaire to assess
      anal continence status and anal incontinence-related quality of life since the
      time of surgery. RESULTS: Of 57 women who underwent an anal sphincteroplasty
      within the study period, 29 met inclusion criteria. Median parity was 3 (range, 1
      7) and 24.5% reported a history of forceps or vacuum-assisted vaginal delivery.
      Presenting symptoms included fecal incontinence (58.6%), flatal incontinence
      (41%), sexual dysfunction (20.7%), and poor body self-image (3.4%). Thirteen
      (45%) women could be contacted by telephone and all agreed to participate.
      Overall, 46.2% of the 13 women who completed the Modified Manchester Health
      Questionnaire reported some form anal of incontinence, whereas 53.8% reported
      complete continence at a mean follow-up of 7.0 +/- 3.6 years. Perioperative
      morbidity was uncommon, and postoperative antibiotics were used in 75.9% of cases
      for a median duration of 8.8 +/- 3.3 days. CONCLUSIONS: Perioperative morbidity
      after overlapping sphincteroplasty for cloacal-like deformities after obstetrical
      injury is rare. Although long-term complete anal continence may be difficult to
      achieve in all cases, good quality of life measures and low symptom severity were
      noted at a mean interval of 7 years after surgery.

PMID- 29324571
TI  - Physical Activity Patterns and Sedentary Behavior in Older Women With Urinary
      Incontinence: an Accelerometer-based Study.
AB  - PURPOSE: Objective physical activity data for women with urinary incontinence are
      lacking. We investigated the relationship between physical activity, sedentary
      behavior, and the severity of urinary symptoms in older community-dwelling women
      with urinary incontinence using accelerometers. MATERIALS AND METHODS: This is a
      secondary analysis of a study that measured physical activity (step count,
      moderate-to-vigorous physical activity time) and sedentary behavior (percentage
      of sedentary time, number of sedentary bouts per day) using a triaxial
      accelerometer in older community-dwelling adult women not actively seeking
      treatment of their urinary symptoms. The relationship between urinary symptoms
      and physical activity variables was measured using linear regression. RESULTS:
      Our cohort of 35 community-dwelling women (median, age, 71 years) demonstrated
      low physical activity (median daily step count, 2168; range, 687-5205) and high
      sedentary behavior (median percentage of sedentary time, 74%; range, 54%-89%).
      Low step count was significantly associated with nocturia (P = 0.02). Shorter
      duration of moderate-to-vigorous physical activity time was significantly
      associated with nocturia (P = 0.001), nocturnal enuresis (P = 0.04), and greater
      use of incontinence products (P = 0.04). Greater percentage of time spent in
      sedentary behavior was also significantly associated with nocturia (P = 0.016).
      CONCLUSIONS: Low levels of physical activity are associated with greater nocturia
      and nocturnal enuresis. Sedentary behavior is a new construct that may be
      associated with lower urinary tract symptoms. Physical activity and sedentary
      behavior represent potential new targets for treating nocturnal urinary tract
      symptoms.

PMID- 29324572
TI  - Epstein-Barr Virus (EBV)-induced B-cell Lymphoproliferative Disorder Mimicking
      the Recurrence of EBV-associated Hemophagocytic Lymphohistiocytosis.
AB  - We describe the case of a 23-month-old male infant with Epstein-Barr virus (EBV)
      associated lymphoproliferative disorder, which mimicked the recurrence of EBV
      associated hemophagocytic lymphohistiocytosis. Chemotherapy with dexamethasone,
      etoposide, and cyclosporine resolved fever, hepatosplenomegaly, and pancytopenia.
      However, on day 81 of illness, the patient developed similar symptoms. Plasma EBV
      DNA levels markedly increased again, but no T-cell clonality was observed. B
      cells were identified to be infected with EBV. He was successfully treated with
      rituximab, dexamethasone and etoposide. When recurrence of EBV-associated
      hemophagocytic lymphohistiocytosis is suspected, performing tests to identify the
      infected cells will enable accurate understanding of the clinical condition,
      resulting in proper treatments.

PMID- 29324573
TI  - Allogeneic Hematopoietic Stem Cell Transplantation for Leukocyte Adhesion
      Deficiency.
AB  - The clinical outcome of allogeneic hematopoietic stem cell transplantation (HSCT)
      was retrospectively analyzed in 6 patients with leukocyte adhesion deficiency. Of
      3 patients transplanted with myeloablative conditioning, 2 patients had complete
      chimerism and 1 patient had mixed chimerism. By contrast, all 3 patients
      transplanted with reduced-intensity conditioning (RIC) had mixed chimerism, one
      of whom progressed to secondary graft failure. All patients with low-level mixed
      chimerism and secondary graft failure were rescued by donor lymphocyte infusion
      or a second HSCT. RIC-HSCT is feasible for leukocyte adhesion deficiency,
      although further refinement/modification of conditioning is required to achieve
      higher donor chimerism levels.

PMID- 29324575
TI  - The Relationship Between Tennis Serve Velocity and Select Performance Measures.
AB  - The purpose of this study was to determine if there was a relationship between
      tennis serve speed and isometric mid-thigh pull (IMTP) kinetic variables;
      countermovement jump height (CMJ Height), shoulder internal and external rotation
      strength and anthropometric measures in elite adolescent tennis players. Twenty
      one elite junior tennis players from the Tennis Australia National Academy were
      recruited for this study (male, n = 12, female, n = 9). Correlations between the
      performance variables and peak tennis serve speed were calculated using a
      Pearson's product-moment correlation coefficient. A significant positive
      correlation was found between peak serve speed and body height (r = 0.80, p <
      0.01), IMTP peak force (r = 0.87, p < 0.01), CMJ Height (r = 0.77, p = < 0.01)
      and impulse at 300ms (r = 0.71, p = < 0.01). A significant, strong correlation
      was found between peak serve speed and impulse at 100ms (r = 0.58, p = < 0.01),
      impulse at 200ms (r = 0.64, p = < 0.01), internal rotation <90 (r = 0.63, p = <
      0.01) and external rotation <90 (r = 0.63, p = < 0.01). Due to the significant
      positive correlations between IMTP variables, CMJ Height and peak serve speed,
      strength and conditioning coaches with access to a force plate should consider
      using the isometric mid-thigh pull in order to athletically profile athletes in
      regards to their strength, power and injury risk.

PMID- 29324574
TI  - Sleep Problem Risk for Adolescents With Sickle Cell Disease: Sociodemographic,
      Physical, and Disease-related Correlates.
AB  - The aims of the current study were to investigate whether SCD incurs an
      additional risk for poor sleep over and above the influence of sociodemographic
      factors (ie, race and sex) during adolescence, and to explore the relationships
      between sociodemographic, physical (ie, age and pubertal status), and disease
      related factors (ie, SCD genotype and hydroxyurea use) on sleep problem risk
      during adolescence. Black adolescents (age, 12 to 17 y) with SCD (n=53) were
      recruited from regional pediatric SCD clinics in the southeast and a sample of
      healthy black adolescents (n=160) were recruited from middle and high schools.
      Regression analyses indicated that SCD was uniquely related to sleeping more, and
      worse sleep quality over and above the influence of sociodemographic factors.
      Having a more severe SCD genotype was related to worse sleep quality and higher
      pubertal status was related to sleeping longer during the week. Results indicate
      the need for systematic assessments of sleep problems, with more a focus on youth
      with more severe genotypes and higher pubertal status. Future research should
      focus on characterizing trajectories of sleep problems in this population,
      identifying key risk factors, and elucidating mechanisms linking risk factors to
      sleep problem risk to aid in tailoring interventions for this population.

PMID- 29324576
TI  - Intermittent Cooling During Judo Training in A Warm/Humid Environment Reduces
      Autonomic and Hormonal Impact.
AB  - The purpose of this study was to identify the effects of superficial cooling on
      physiological responses while training in a warm, humid environment during an
      international judo training camp. Sixteen judokas (8 women and 8 men)
      participated in the experiment. Four high-level women and four men were randomly
      assigned to wear a cooling vest (vest group, VG) during the recovery periods
      within a training session (i.e. 8 bouts of 5 min fighting with 5 min rest) and up
      to 10 min after the session, while the remaining athletes in the control group
      (CG) trained without the use of any cooling aids. No differences between groups
      were reported in well-being prior to the session or in perceived fatigue
      following the session. The temperature was increased after the training session
      (p=0.02) without significant differences between groups; however, CG demonstrated
      a moderate effect size (ES=0.95, 90% confidence interval [CI] from 0.09 to 1.82;
      probability of superiority [PS]=74.9%) in contrast to the small effect for VG
      (ES=0.28, 90% CI from -0.55 to 1.11; PS=57.9%). There were time * group
      interactions for heart rate variability (HRV; lnRMSSD) (p<0.01; VG vs. CG,
      PS=79.0%) and the dehydroepiandrosterone-cortisol ratio (DHEA/C ratio) (p=0.04;
      VG vs. CG, PS=99.9%). VG preserved the cardiac autonomic control (p>0.05; ES=
      0.06, 90% CI=-0.88 to 0.76; PS=51.7%) compared to the large decrement of CG
      (p<0.05; ES=-1.18, 90% CI=-2.07 to -0.29; PS=74.9%). Furthermore, VG showed an
      increase of DHEA/C (p<0.01) from pre- to post-session based on a moderate
      decrease of cortisol (p>0.05; ES=-0.67, 90% CI=-1.52 to 0.17; PS=68.2%) with a
      concomitant small increase of DHEA (p>0.05; ES=0.46, 90%CI=-0.38 to 1.29;
      PS=62.7%). Conversely, the control group showed a moderate effect for increased
      DHEA and a small effect for increased cortisol following training. No significant
      interactions or main effects were shown for isometric handgrip values. Cooling
      vests diminished the cardiovascular strain and hormonal impact of the judo
      training session in high-level athletes and may be considered for recovery
      purposes during exercise in warm/humid environments.

PMID- 29324577
TI  - Physical Fitness Performance of Young Professional Soccer Players Does Not Change
      During Several Training Seasons in a Spanish Elite Reserve Team: Club Study, 1996
      2013.
AB  - Los Arcos, A and Martins, J. Physical fitness performance of young professional
      soccer players does not change during several training seasons in a Spanish elite
      reserve team: club study, 1996-2013. J Strength Cond Res 32(9): 2577-2583, 2018
      The purpose of this study was to assess the changes in physical fitness
      performance in young professional soccer players during several training seasons
      in a Spanish elite reserve team. Physical test values (i.e., vertical jump test,
      straight line sprint test, and discontinuous and progressive submaximal running
      test) of 97 young professional soccer players who belonged for at least 2
      consecutive seasons to the reserve team of a Spanish professional team from 1996
      to 2013 were analyzed. A distinction was made between the soccer players who were
      promoted to the Spanish first/second divisions (n = 38) and those who were not (n
      = 59) (until the end of the 2016/2017 season). Players were also classified
      according to their playing positions. Independently of the competitive level
      reached and the playing position, the variability of the fitness performance was
      limited (coefficient of variation <6%) and the players did not improve their
      fitness values (effect size <= small) from the first to the last season in which
      they were enrolled in the team (after 2-4 seasons). During the last stage of
      training in an elite soccer academy, young professional soccer players achieve a
      very similar physical fitness performance when their soccer competence is
      evaluated, and other soccer performance factors are those which make them stand
      out for selection.

PMID- 29324578
TI  - Training Volume, Not Frequency, Indicative of Maximal Strength Adaptations to
      Resistance Training.
AB  - Colquhoun, RJ, Gai, CM, Aguilar, D, Bove, D, Dolan, J, Vargas, A, Couvillion, K,
      Jenkins, NDM, and Campbell, BI. Training volume, not frequency, indicative of
      maximal strength adaptations to resistance training. J Strength Cond Res 32(5):
      1207-1213, 2018-To compare the effects of a high versus a moderate training
      frequency on maximal strength and body composition. Twenty-eight young, healthy
      resistance-trained men were randomly assigned to either: 3* per week (3*; n = 16)
      or 6* per week (6*; n = 12). Dependent variables (DVs) assessed at baseline and
      after the 6-week training intervention included: squat 1 repetition maximum
      (SQ1RM), bench press 1RM (BP1RM), deadlift 1RM (DL1RM), powerlifting total (PLT),
      Wilk's coefficient (WC), fat-free mass (FFM), and fat mass. Data for each DV were
      analyzed using a 2 * 2 between-within factorial repeated-measures analysis of
      variance. There was a main effect for time (p < 0.001) for SQ1RM (3*: +16.8 kg;
      6*: +16.7 kg), BP1RM (3*: +7.8 kg; 6*: +8.8 kg), DL1RM (3*: +19 kg; 6*: +21 kg),
      PLT (3*: +43.6 kg; 6*: +46.5 kg), WC (3*: +27; 6*: +27.1), and FFM (3*: +1.7 kg;
      6*: +2.6 kg). There were no group * time interactions or main effects for group.
      The primary finding was that 6 weeks of resistance training led to significant
      increases in maximal strength and FFM. In addition, it seems that increased
      training frequency does not lead to additional strength improvements when volume
      and intensity are equated. High-frequency (6* per week) resistance training does
      not seem to offer additional strength and hypertrophy benefits over lower
      frequency (3* per week) when volume and intensity are equated. Coaches and
      practitioners can therefore expect similar increases in strength and lean body
      mass with both 3 and 6 weekly sessions.

PMID- 29324579
TI  - Traditional Versus Suspended Push-up Muscle Activation in Athletes and Sedentary
      Women.
AB  - Syed-Abdul, MM, Soni, DS, Miller, WM, Johnson, RJ, Barnes, JT, Pujol, TJ, and
      Wagganer, JD. Traditional versus suspended push-up muscle activation in athletes
      and sedentary women. J Strength Cond Res 32(7): 1816-1820, 2018-Many strength
      training programs incorporate push-up exercises, which primarily activate upper
      body muscles. Past data support the fact that shoulder girdle muscles (i.e.,
      triceps (T) and anterior deltoids [AD]) exhibit greater electromyography (EMG)
      activity when a push-up is performed on an unstable (i.e., suspended [SP]) vs.
      stable (i.e., traditional [TD]) surface (). Sixty-nine healthy female volunteers
      (soccer players [SO], n = 24; gymnasts [GY], n = 21; sedentary [SE], n = 24)
      performed three TD and three SP push-ups. Muscle activation, expressed as
      absolute integral (mV), was measured using EMG analysis. Significant increases in
      muscle activation were exhibited by GY (TD: p < 0.01 and SP: p < 0.001) and SO
      (TD: p < 0.05 and SP: p < 0.05) compared to SE for the T muscle. Only SO (p <
      0.05) exhibited significantly higher muscle activation during the SP versus TD.
      For the AD, values were significantly higher for SO (TD: p < 0.001 and SP: p <
      0.001) and GY (TD: p < 0.01 and SP: p < 0.01) compared to the SE group. In
      addition, significantly higher values were exhibited by SO compared with GY
      during TD push-ups (p < 0.01). Both the SO (p < 0.05) and GY (p < 0.05) group
      exhibited significantly higher values during SP versus TD push-ups. Finally,
      values were significantly higher for the AD compared to the T muscle only in the
      SO group during TD (p < 0.01) and SP (p < 0.05) push-ups. Data from this study
      for trained women (i.e., SO) are consistent with previous studies, whereas for
      untrained women (i.e., SE) the findings differed during TD and SP push-ups for
      both muscles. Differences were also observed between female SO and GY are
      unexplainable and therefore need further investigation.

PMID- 29324580
TI  - Relationship Between Skating Economy and Performance During a Repeated-Shift Test
      in Elite and Subelite Ice Hockey Players.
AB  - Lamoureux, NR, Tomkinson, GR, Peterson, BJ, and Fitzgerald, JS. Relationship
      between skating economy and performance during a repeated-shift test in elite and
      subelite ice hockey players. J Strength Cond Res 32(4): 1109-1113, 2018-The
      purpose of this study was to determine the importance of skating economy to
      fatigue during repeated high-intensity efforts of a simulated ice hockey shift.
      Forty-five collegiate and Junior A male ice hockey players (aged 18-24 years)
      performed a continuous graded exercise test using a skate treadmill. Breath-by
      breath data for oxygen consumption (V[Combining Dot Above]O2) and respiratory
      exchange ratio were collected and used to derive energy expenditure (EE) averaged
      over the final 10 seconds of each stage. Economy was determined as the slope of
      the regression line relating V[Combining Dot Above]O2 and EE against skating
      speed separately. Participants also completed 8 bouts of maximal ice skating
      through a course designed to simulate typical shift, with timing gates
      determining first half, second half, and total fatigue decrement, calculated by a
      percent decrement score. Partial correlation was used to determine the
      association between economy measures and decrement during the repeated-shift
      test. Twenty-six participants met inclusion criteria and were included in data
      analysis. Skating economy measures (both relative V[Combining Dot Above]O2 and
      EE) were very likely moderate positive correlates of total fatigue decrement (r
      [95% confidence interval]: V[Combining Dot Above]O2, 0.46 [0.09, 0.72] and EE,
      0.44, [0.06, 0.71]) but not with first or second gate decrement. Our results
      indicate that skating economy plays an important role in fatigue resistance over
      repeated on-ice sprints designed to simulate a typical shift. This supports the
      use of technical skating coaching and training techniques to enhance skating
      economy as a means of improving ice hockey performance.

PMID- 29324581
TI  - The silent struggles of survivorship in cancer.

PMID- 29324582
TI  - Quality measures in acute kidney injury.
AB  - PURPOSE OF REVIEW: Quality measure assessment and reporting is evolving in end
      stage renal disease care and is inchoate in ambulatory nephrology clinic care.
      Acute kidney injury (AKI) quality measures have not received sufficient
      attention, yet deserve consideration in view of the substantial proportion of
      effort nephrology providers devote to AKI care. RECENT FINDINGS: Accumulating
      literature permits consideration of timing of nephrology consultation, follow-up
      after AKI hospitalization, early detection, medication dosing, hospital
      readmissions and length of stay, cost, and mortality as potential AKI quality
      measures. SUMMARY: We review candidate AKI quality measures and assess the
      strength of evidence supporting the use of each measure as a standard for AKI
      care.

PMID- 29324583
TI  - An explanatory and predictive model of the variation in esophageal cancer
      incidence on the basis of changes in the exposure to risk factors.
AB  - Variations in the exposure to risk factors may be used to explain past cancer
      trends and to predict its future burden. This study aimed to develop a model to
      describe and predict the variation of esophageal cancer incidence in 1995-2005,
      taking into account changes in exposures to risk factors. We adapted an existing
      model to calculate the expected variation in the number of esophageal cancer
      cases, between 1995 and 2005, in Australia, Japan, Italy, Portugal, the UK, and
      the USA, because of changes in exposures to risk factors, taking into account the
      corresponding lag times. Analyses were based on country-specific data of cancer
      incidence and exposures to risk factors. We computed 95% credibility intervals
      through Monte Carlo simulation methods. Absolute deviations between the number of
      cases predicted and those observed in 2005 ranged between 1.8% in Japan and 23.6%
      in the UK among men and 0.0% in Japan and 18.0% in Australia among women. In
      Italy and Japan, deviations did not exceed 3%. The UK registered the worst model
      performance. The variation in esophageal cancer incidence was mainly influenced
      by changes in fruit and red meat intake, and BMI. For nearly half of the sex
      specific and histological type-specific predictions performed, credibility
      intervals included the observed number of cases. This study proposes a framework
      for the analysis of the contribution of changes in exposure to different factors
      to esophageal cancer incidence trends and for long-term predictions at a
      population level.

PMID- 29324584
TI  - Maternal Serum Eye Drops in the Management of Pediatric Persistent Corneal
      Epithelial Defects: A Case Series.
AB  - PURPOSE: We report our experience with the use of maternally derived serum eye
      drops as adjunctive treatment in the management of pediatric persistent corneal
      epithelial defects. METHODS: Five eyes of 4 patients were identified in a
      retrospective review of pediatric patients with persistent corneal epithelial
      defects who received maternal serum drops. Diagnoses associated with the defects
      comprised pontine tegmental cap dysplasia with bilateral cranial nerve V1, V2,
      V3, and VII palsies; pontine tegmental cap dysplasia with left cranial nerve V1,
      VII, and VIII palsies; traumatic left cranial nerve II, V1, V2, and VI palsies
      due to a basilar skull fracture; and Stevens-Johnson syndrome with ocular
      involvement. We evaluated the feasibility of using maternally derived serum
      drops; thus, we looked at the ability to prepare and tolerate the drops as well
      as any complications that could have been associated with treatment. Other data
      collected included visual acuity, corneal examination, and current and previous
      treatments. RESULTS: Both the duration of therapy and time of follow-up ranged
      from 5 to 28 months. All patients experienced improvement or resolution of their
      corneal epithelial defects within 3 weeks of initiating serum eye drops.
      Furthermore, there were no adverse effects from the use of allogeneic serum
      drops. CONCLUSIONS: Maternal serum eye drops are a well-tolerated and potentially
      beneficial addition to the management of pediatric persistent corneal epithelial
      defects.

PMID- 29324586
TI  - Ten-year experience of transjugular intrahepatic portosystemic shunt for
      noncirrhotic portal hypertension.
AB  - BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) is considered to
      be well suited for the treatment of noncirrhotic portal hypertension (NCPHT)
      because of a usually severe portal hypertension (PHT) and a mild liver failure,
      but very less data are available. PATIENTS AND METHODS: Records of patients
      referred for TIPS between 2004 and 2015 for NCPHT were reviewed. No patient
      should have clinical or biological or histological features of cirrhosis.
      RESULTS: Twenty-five patients with a wide variety of histological lesions
      (sinusoidal dilatations, granulomatosis, regenerative nodular hyperplasia,
      obliterative portal venopathy, or subnormal liver) and a wide variety of
      associated diseases (thrombophilia, sarcoidosis, common variable
      immunodeficiency, scleroderma, Castleman's disease, early primitive biliary
      cirrhosis, congenital liver fibrosis, chemotherapy, purinethol intake, and
      congenital varices) were included. Two complications occurred during the
      procedure: one periprosthetic hematoma and the other misposition of a covered
      stent. During the first month, two other patients had an early thrombosis,
      another had induced encephalopathy, and one died of early rebleeding. Two of
      these complications occurred in patients with cavernoma. With a mean follow-up of
      39 months, 10 patients experienced at least one episode of spontaneous
      encephalopathy, with three of these patients requiring a stent reduction. Five
      patients had a recurrence of their initial symptoms, and one had an asymptomatic
      hemodynamic dysfunction. CONCLUSION: TIPS is effective in NCPHT but can be
      technically difficult, especially in the case of cavernoma. Good liver function
      does not prevent the occurrence of long-term encephalopathy.

PMID- 29324585
TI  - Effects of metabolic syndrome on arterial function in different age groups: the
      Advanced Approach to Arterial Stiffness study.
AB  - OBJECTIVE: The aim of the Advanced Approach to Arterial Stiffness study was to
      compare arterial stiffness measured simultaneously with two different methods in
      different age groups of middle-aged and older adults with or without metabolic
      syndrome (MetS). The specific effects of the different MetS components on
      arterial stiffness were also studied. METHODS: This prospective, multicentre,
      international study included 2224 patients aged 40 years and older, 1664 with and
      560 without MetS. Patients were enrolled in 32 centres from 18 European countries
      affiliated to the International Society of Vascular Health & Aging. Arterial
      stiffness was evaluated using the cardio-ankle vascular index (CAVI) and the
      carotid-femoral pulse wave velocity (CF-PWV) in four prespecified age groups: 40
      49, 50-59, 60-74, 75-90 years. In this report, we present the baseline data of
      this study. RESULTS: Both CF-PWV and CAVI increased with age, with a higher
      correlation coefficient for CAVI (comparison of coefficients P < 0.001). Age
      adjusted and sex-adjusted values of CF-PWV and CAVI were weakly intercorrelated
      (r = 0.06, P < 0.001). Age-adjusted and sex-adjusted values for CF-PWV but not
      CAVI were higher in presence of MetS (CF-PWV: 9.57 +/- 0.06 vs. 8.65 +/- 0.10, P
      < 0.001; CAVI: 8.34 +/- 0.03 vs. 8.29 +/- 0.04, P = 0.40; mean +/- SEM; MetS vs.
      no MetS). The absence of an overall effect of MetS on CAVI was related to the
      heterogeneous effects of the components of MetS on this parameter: CAVI was
      positively associated with the high glycaemia and high blood pressure components,
      whereas lacked significant associations with the HDL and triglycerides components
      while exhibiting a negative association with the overweight component. In
      contrast, all five MetS components showed positive associations with CF-PWV.
      CONCLUSION: This large European multicentre study reveals a differential impact
      of MetS and age on CAVI and CF-PWV and suggests that age may have a more
      pronounced effect on CAVI, whereas MetS increases CF-PWV but not CAVI. This
      important finding may be due to heterogeneous effects of MetS components on CAVI.
      The clinical significance of these original results will be assessed during the
      longitudinal phase of the study.

PMID- 29324587
TI  - Linkage to care of HbsAg-positive and anti-HCV-positive patients after a
      systematic screening approach in the German primary care setting.
AB  - BACKGROUND: Identification of previously unknown cases is important to lower the
      burden of chronic hepatitis B and C infection. However, a screening program in
      the primary care setting has not yet been established. Therefore, a systematic
      screening project was conducted in 21 008 patients (Wolffram and colleagues).
      Here, we describe linkage to care of identified HbsAg-positive and anti-hepatitis
      C virus (HCV)-positive patients. METHODS: General practitioners characterized
      further medical care by a standardized questionnaire. Data of 48/110 HbsAg
      positive and 114/199 anti-HCV-positive patients were available. An APRI index
      more than 2 or up to 0.5 indicated the presence of cirrhosis or the absence of
      fibrosis. RESULTS: APRI was calculated in 32/48 hepatitis B virus (HBV) patients
      (>2: n=1; <=0.5: n=29) and 34/114 HCV patients (>2: n=4; <=0.5: n=23). The
      general practitioners were already aware of the positive HBsAg and anti-HCV-test
      in 13/48 and 59/114 patients, respectively.For 29/35 newly diagnosed HBV patients
      and 26/55 HCV patients, further diagnostics were initiated: ultrasound 77 versus
      38%, liver biopsy 20 versus 4%, and gastroscopy 20 versus 7%.Antiviral treatment
      was initiated in 5/35 HBV cases and in 10/55 HCV patients.A family screening was
      initiated in 22/35 HBV versus 13/55 HCV index patients and showed one additional
      HbsAg-positive and two anti-HCV-positive cases.Diagnostic procedures differed
      significantly between anti-HCV-positive and HbsAg-positive patients (P<0.001 for
      APRI, ultrasound, and family screening; P=0.03 for liver biopsy). CONCLUSION:
      Diagnostic procedures should be improved for hepatitis C-infected patients. The
      APRI index was only of limited value in the primary care setting.

PMID- 29324588
TI  - Both alpha-1-antitrypsin Z phenotypes and low caeruloplasmin levels are over
      represented in alcohol and nonalcoholic fatty liver disease cirrhotic patients
      undergoing liver transplant in Ireland.
AB  - OBJECTIVES: Alcoholic liver disease and nonalcoholic fatty liver disease (NAFLD)
      are steatotic liver diseases and major causes of cirrhosis. Only a minority of
      patients with risk factors develop cirrhosis and genetic cofactors may be
      important in pathogenesis. Mutations in the Wilson's and alpha-1-antitrypsin
      genes are not uncommon and we speculated that they may act as cofactors. METHODS:
      We investigated alpha-1-antitrypsin phenotyes and caeruloplasmin levels in
      patients undergoing elective liver transplantation. We compared patients with
      alcohol and NAFLD with nonsteatotic liver disease patients: viral hepatitis B or
      C, autoimmune hepatitis, primary biliary cholangitis and primary sclerosing
      cholangitis. RESULTS: Two hundred and thirty-one patients were included in the
      study. Pretransplant caeruloplasmin levels and alpha-1-antitrypsin phenotypes
      were available in 197 and 112 patients, respectively. alpha-1-Antitrypsin Z
      phenotypes were significantly more common in the alcohol and NAFLD group: 12/56
      versus 3/56 (P<0.05). Serum caeruloplasmin (0.3+/-0.01 vs. 0.39+/-0.01 g/l,
      P<0.01) and serum copper levels (13.5+/-0.9 vs. 19.3+/-0.9 MUmol/l, P<0.01) were
      significantly lower in the alcohol and NAFLD patients compared with the viral and
      autoimmune patients. CONCLUSION: In this study, we found the alpha-1-antitrypsin
      Z phenotype was more common, and serum caeruloplasmin and copper levels were
      lower in patients with fatty liver diseases. We suggest that mutations in the
      alpha-1-antitrypsin and Wilson's genes may act as cofactors in the pathogenesis
      of fatty liver diseases.

PMID- 29324589
TI  - Percutaneous endoscopic gastrostomy with and without jejunal extension in
      patients with amyotrophic lateral sclerosis.
AB  - BACKGROUND AND AIMS: Amyotrophic lateral sclerosis (ALS) is a fatal degenerative
      disease of the motor nervous system, which is associated with severe loss of
      weight. Enteral nutrition through percutaneous endoscopic gastrostomy (PEG) or
      percutaneous endoscopic gastrostomy with jejunal extension (PEG-J) is generally
      recommended upon disease progression. There is no standard endoscopic method that
      should preferentially be performed. The aim of this study was to compare the
      number of adverse events, complication-free survival (CFS), and overall survival
      (OS) in patients who received PEG or PEG-J. PATIENTS AND METHODS: All patients
      with ALS presenting for PEG or PEG-J placement to the Endoscopic Unit of Hannover
      Medical School, Germany, between 2009 and 2015 were retrospectively analyzed.
      RESULTS: Demographics were similar for patients receiving PEG (n=43) and PEG-J
      (n=39). The median intervention time and the absolute dose of propofol were
      significantly longer and, respectively, higher for patients with PEG-J (P=0.001
      and 0.013). Intervention-related complications leading to hospitalization were
      significantly more frequent in patients who received PEG-J (36 vs. 4, P=0.001).
      The median CFS was significantly shorter in patients who received PEG-J compared
      with PEG (5 vs. 14 months, P=0.007). There was no difference in OS. CONCLUSION:
      Intervention-related complications were more frequent and the median CFS was
      shorter in patients who received PEG-J, whereas there was no difference in OS.
      Given the poor prognosis of patients with ALS, our data provide first evidence
      that PEG might be the better tolerable option, with fewer complications. The
      decision on which nutritional system is implanted should be evaluated
      individually.

PMID- 29324590
TI  - REPEATABILITY OF CHOROIDAL THICKNESS MEASUREMENTS ASSESSED WITH SWEPT-SOURCE
      OPTICAL COHERENCE TOMOGRAPHY IN HEALTHY AND DIABETIC INDIVIDUALS.
AB  - PURPOSE: To assess the intrasession repeatability of choroidal thickness
      measurements obtained using swept-source optical coherence tomography in Type 2
      diabetic (T2D) patients and healthy controls. METHODS: This was a single-center,
      prospective, observational, cross-sectional study with consecutive inclusion of
      33 healthy subjects and 43 T2D patients. Subjects underwent three consecutive
      swept-source optical coherence tomography scans in a single session. After
      automatic delineation of the choroid, subfoveal choroidal thickness, and
      thickness at 500-MUm intervals up to 2,500 MUm nasal and temporal from the fovea
      were measured using the software caliper by the same operator. Intraclass
      correlation coefficients (ICCs), coefficients of variation, and test-retest
      variability were calculated. RESULTS: Mean subfoveal choroidal thickness in
      healthy subjects and in T2D patients was 229.97 +/- 79.9 and 192.67 +/- 74.3 MUm,
      respectively (P = 0.013). All intrasession intraclass correlation coefficients
      were higher than 0.95 and 0.99, respectively. Coefficients of variations were
      less than 4.4% and 1.8%, respectively. Test-retest variability ranged from 0.76
      MUm to 11.12 MUm and 0.64 MUm to 6.29 MUm, respectively. No significant
      differences were found in the intrasession repeatability of any choroidal
      measurement between healthy subjects and T2D patients. CONCLUSION: Swept-source
      optical coherence tomography provided excellent intrasession repeatability of
      choroidal thickness measurements in healthy subjects and T2D patients.

PMID- 29324593
TI  - INCIDENCE AND LONG-TERM VISUAL ACUITY OUTCOMES OF RETINAL PIGMENT EPITHELIUM
      TEARS AFTER INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR TREATMENT OF
      NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.
AB  - PURPOSE: To report the incidence of retinal pigment epithelium tears in eyes
      treated with aflibercept for neovascular age-related macular degeneration and
      compare it with ranibizumab, and to describe long-term visual outcomes of retinal
      pigment epithelium tears after intensive anti-vascular endothelial growth factor
      treatment. METHODS: Retrospective analysis of clinical charts, spectral domain
      optical coherence tomography and fundus fluorescein angiography imaging of
      consecutive naive patients treated with intravitreal aflibercept or ranibizumab
      for neovascular age-related macular degeneration. RESULTS: Eight hundred
      consecutive eyes were included in the study (300 treated with ranibizumab and 500
      with aflibercept) with 34.0 +/- 9.1 months of follow-up. The incidence of tears
      in the aflibercept group was 3.2% and 2.3% after ranibizumab (P = 0.52). Twenty
      nine eyes with retinal pigment epithelium tears were followed for a mean of 30.76
      months. Visual acuity at baseline was 20/100 (50.7 +/- 19.3 Early Treatment
      Diabetic Retinopathy Study letters) and 20/200 (36.1 +/- 26.1 Early Treatment
      Diabetic Retinopathy Study letters) at the end of follow-up. The mean number of
      injection was 7.3 at 12 months and 13.9 +/- 8.1 at the end of the study. The
      number of injections positively correlated with the final visual outcome.
      CONCLUSION: There was a low rate of retinal pigment epithelium tears after
      aflibercept injections, similar to ranibizumab. The correlation between the
      number of anti-vascular endothelial growth factors received and visual outcomes
      supports the need for continuing anti-vascular endothelial growth factor therapy.

PMID- 29324591
TI  - VISUALIZATION FROM INTRAOPERATIVE SWEPT-SOURCE MICROSCOPE-INTEGRATED OPTICAL
      COHERENCE TOMOGRAPHY IN VITRECTOMY FOR COMPLICATIONS OF PROLIFERATIVE DIABETIC
      RETINOPATHY.
AB  - PURPOSE: To evaluate the use of live volumetric (4D) intraoperative swept-source
      microscope-integrated optical coherence tomography in vitrectomy for
      proliferative diabetic retinopathy complications. METHODS: In this prospective
      study, we analyzed a subgroup of patients with proliferative diabetic retinopathy
      complications who required vitrectomy and who were imaged by the research swept
      source microscope-integrated optical coherence tomography system. In near real
      time, images were displayed in stereo heads-up display facilitating
      intraoperative surgeon feedback. Postoperative review included scoring image
      quality, identifying different diabetic retinopathy-associated pathologies and
      reviewing the intraoperatively documented surgeon feedback. RESULTS: Twenty eyes
      were included. Indications for vitrectomy were tractional retinal detachment (16
      eyes), combined tractional-rhegmatogenous retinal detachment (2 eyes), and
      vitreous hemorrhage (2 eyes). Useful, good-quality 2D (B-scans) and 4D images
      were obtained in 16/20 eyes (80%). In these eyes, multiple diabetic retinopathy
      complications could be imaged. Swept-source microscope-integrated optical
      coherence tomography provided surgical guidance, e.g., in identifying dissection
      planes under fibrovascular membranes, and in determining residual membranes and
      traction that would benefit from additional peeling. In 4/20 eyes (20%),
      acceptable images were captured, but they were not useful due to high tractional
      retinal detachment elevation which was challenging for imaging. CONCLUSION: Swept
      source microscope-integrated optical coherence tomography can provide important
      guidance during surgery for proliferative diabetic retinopathy complications
      through intraoperative identification of different complications and facilitation
      of intraoperative decision making.

PMID- 29324592
TI  - FREQUENT SUBCLINICAL MACULAR CHANGES IN COMBINED BRAF/MEK INHIBITION WITH HIGH
      DOSE HYDROXYCHLOROQUINE AS TREATMENT FOR ADVANCED METASTATIC BRAF MUTANT
      MELANOMA: Preliminary Results From a Phase I/II Clinical Treatment Trial.
AB  - PURPOSE: To assess the potential ocular toxicity of a combined BRAF inhibition
      (BRAFi) + MEK inhibition (MEKi) + hydroxychloroquine (HCQ) regime used to treat
      metastatic BRAF mutant melanoma. METHODS: Patients with stage IV metastatic
      melanoma and BRAF V600E mutations (n = 11, 31-68 years of age) were included.
      Treatment was with oral dabrafenib, 150 mg bid, trametinib, 2 mg/day, and HCQ,
      400 mg to 600 mg bid. An ophthalmic examination, spectral domain optical
      coherence tomography, near-infrared and short-wavelength fundus autofluorescence,
      and static perimetry were performed at baseline, 1 month, and q/6 months after
      treatment. RESULTS: There were no clinically significant ocular events; there was
      no ocular inflammation. The only medication-related change was a separation of
      the photoreceptor outer segment tip from the apical retinal pigment epithelium
      that could be traced from the fovea to the perifoveal retina noted in 9/11 (82%)
      of the patients. There were no changes in retinal pigment epithelium melanization
      or lipofuscin content by near-infrared fundus autofluorescence and short
      wavelength fundus autofluorescence, respectively. There were no inner retinal or
      outer nuclear layer changes. Visual acuities and sensitivities were unchanged.
      CONCLUSION: BRAFi (trametinib) + MEKi (dabrafenib) + HCQ causes very frequent,
      subclinical separation of the photoreceptor outer segment from the apical retinal
      pigment epithelium without inner retinal changes or signs of inflammation. The
      changes suggest interference with the maintenance of the outer retinal barrier
      and/or phagocytic/pump functions of the retinal pigment epithelium by effective
      MEK inhibition.

PMID- 29324594
TI  - INTRAOPERATIVE AND POSTOPERATIVE COMPLICATIONS IN PHACOVITRECTOMY FOR EPIRETINAL
      MEMBRANE AND MACULAR HOLE: A Clinical Audit of 1,000 Consecutive Eyes.
AB  - PURPOSE: The aim of this study was to report the intraoperative and postoperative
      complications of phacovitrectomy for epiretinal membrane (ERM) and macular hole
      (MH). METHODS: This was a retrospective audit of 1,052 phacovitrectomy operations
      (410 for ERM and 642 for MH) by the same surgical team between 1998 and 2017.
      Outcome measures included rates of intraoperative anterior segment and posterior
      segment complications such as posterior capsule rupture and retinal breaks. A
      subgroup analysis of 189 procedures in which postoperative complications were
      rigorously recorded was also undertaken. RESULTS: The rate of posterior capsule
      rupture was 2.2%, with no difference between ERM and MH (1.7 vs. 2.5%; P = 0.40).
      Iatrogenic retinal tears were more common in MH than in ERM surgery (15.6 vs.
      6.8%; P < 0.001). The chance of one or more anterior segment or posterior segment
      intraoperative complications occurring (excluding iatrogenic retinal breaks) was
      not associated with: indication for surgery, grade of surgeon, gauge of surgery,
      surgical machine, diabetic status, patient sex, or patient age. Subgroup analysis
      showed postoperative events as follows: posterior capsular opacification 10.6%
      (20/189), posterior synechiae 4.2% (8/189), uveitis 2.1% (4/189), angle closure
      glaucoma 1.6% (3/189), and rhegmatogenous retinal detachment 1.1% (2/189).
      CONCLUSION: Phacovitrectomy seems to be safe in phakic patients with ERM or MH,
      performed either by fellows or consultants. It avoids the requirement for repeat
      surgery and is more cost and resource efficient.

PMID- 29324596
TI  - Preterm Delivery and Low Birth Weight Among Neonates Conceived With
      Intracytoplasmic Sperm Injection Compared With Conventional In Vitro
      Fertilization.
AB  - OBJECTIVE: To examine the prevalence of prematurity and low birth weight (LBW)
      among singletons conceived with intracytoplasmic sperm injection (ICSI) compared
      with those conceived with conventional in vitro fertilization (IVF). METHODS:
      Using the Society for Assisted Reproductive Technology Clinic Outcomes Reporting
      System, we conducted a retrospective cohort study of women undergoing a first,
      fresh autologous ICSI or conventional IVF cycle from 2004 to 2013. Singleton live
      births were included in the analysis. Primary outcomes were preterm delivery and
      LBW. Secondary outcomes were very preterm delivery, preterm LBW, term LBW, and
      very LBW. Logistic regression models and propensity score matching were used to
      compare perinatal outcomes between ICSI and IVF cycles. Subset analyses were
      performed after stratification by sperm source, male factor infertility, and
      female prognosis. RESULTS: Of the 90,401 cycles included in the analysis, ICSI
      was used in 60,719 (67.2%) and conventional IVF was used in 29,682 (32.8%). After
      propensity score matching and covariate adjustment, the two groups had similar
      odds of preterm delivery (adjusted odds ratio [OR] 1.02, 95% CI 0.89-1.18) and
      LBW (adjusted OR 0.92, 95% CI 0.78-1.10). Using the matched data set, subset
      analyses demonstrated no significant association between the method of
      fertilization and the examined perinatal outcomes. CONCLUSION: Rates of preterm
      delivery and LBW were similar between pregnancies conceived with ICSI and
      conventional IVF after propensity score matching and stratifying by baseline
      patient characteristics. Previously reported differences in these outcomes were
      likely secondary to patients' inherent risk factors rather than the fertilization
      procedure itself.

PMID- 29324595
TI  - Association of Pharmacologic Treatment of Urgency Urinary Incontinence With Sleep
      Quality and Daytime Sleepiness.
AB  - OBJECTIVE: To evaluate the association between pharmacologic therapy for urgency
      urinary incontinence (UUI) and sleep quality. METHODS: We conducted a planned
      secondary data analysis of sleep outcomes in a previously conducted multicenter,
      double-blind, 12-week randomized trial of pharmacologic therapy for urgency
      predominant incontinence among community-dwelling women self-diagnosed using the
      3-Incontinence Questions questionnaire. Participants (N=645) were assigned
      randomly to 4-8 mg antimuscarinic therapy daily or placebo. At baseline and 12
      weeks, participants completed a validated voiding diary to evaluate incontinence
      and voiding symptoms, the Pittsburgh Sleep Quality Index to evaluate sleep
      quality, and the Epworth Sleepiness Scale to evaluate daytime sleepiness.
      RESULTS: Mean (SD) age was 56 (+/-14) years, 68% were white, and 57% had poor
      sleep quality (Pittsburgh Sleep Quality Index score greater than 5). Mean
      frequency of any urinary incontinence and UUI was 4.6 and 3.9 episodes/d,
      respectively. After 12 weeks, women randomized to the antimuscarinic group
      reported greater decrease compared with the placebo group in UUI frequency (0.9
      episodes/d; P<.001) and diurnal and nocturnal voiding frequency (P<.05). As
      compared with the placebo group, women in the antimuscarinic group also reported
      greater improvement in sleep quality (total Pittsburgh Sleep Quality Index score
      0.48; P=.02) with greater improvement in sleep duration and sleep efficiency
      subscales (P<.05). The intervention did not affect daytime sleepiness.
      CONCLUSION: Pharmacologic treatment of UUI is associated with decreased
      incontinence frequency and nocturia and improvement in overall sleep quality,
      sleep duration, and sleep efficiency. CLINICAL TRIAL REGISTRATION:
      ClinicalTrials.gov, NCT00862745.

PMID- 29324597
TI  - Internal Podalic Version and Breech Extraction: Enhancing Realistic Sensations in
      a Simulation Model.
AB  - BACKGROUND: Experience with internal podalic version and breech extraction is
      diminishing, especially in the younger generation of obstetricians. Simulation
      training is essential to teach and maintain these skills. INSTRUMENT: We present
      a mannequin-based simulation method that enhances realistic sensations during
      training. EXPERIENCE: By positioning the fetal mannequin into a thin plastic bag
      filled with water, the impression of palpating, grabbing, and pulling the fetal
      feet through the plastic bag is similar to reaching feet through intact
      membranes. The unique approach of this realistic simulation model makes the
      experience fun and memorable, which contributes to the didactic value and success
      of the model. CONCLUSION: The simulation model we present mimics the situation
      and sensation obstetricians experience while performing internal podalic version
      and breech extraction.

PMID- 29324598
TI  - Adoption of Minimally Invasive Surgery and Decrease in Surgical Morbidity for
      Endometrial Cancer Treatment in the United States.
AB  - OBJECTIVE: To assess how the widespread adoption of minimally invasive surgery in
      the United States is associated with changes in 30-day morbidity and mortality in
      endometrial cancer treatment. METHODS: In this retrospective cohort study, the
      American College of Surgeons' National Surgical Quality Improvement Project
      database for 2008-2014 was reviewed for patients who had undergone surgery for
      endometrial cancer according to their primary Current Procedural Terminology
      (CPT) codes. Women with CPT codes for advanced cancer or with disseminated
      disease were excluded. A trend analysis across the time period by surgical
      approach (open surgery through laparotomy, vaginal surgery, and minimally
      invasive surgery) was performed using a Cochran-Armitage test for trend. Thirty
      day surgical outcomes were compared between patients who had minimally invasive
      surgery and open surgery. Inverse probability of treatment weighting models were
      used to investigate the independent effect of minimally invasive surgery on 30
      day outcomes. RESULTS: Overall, 12,283 patients met the inclusion criteria. A
      significant implementation of minimally invasive surgery (24.2-71.4%) and a
      concomitant decrease in open surgery through laparotomy (71.1-26.4%) were
      observed from 2008 to 2014 (both P<.001). Rate of vaginal surgery did not change
      over time (1.5-2.2%, P=.06). After adjusting for possible confounders, open
      surgery (compared with minimally invasive surgery) was independently associated
      with increased odds of major complications (n=347 versus n=274, adjusted odds
      ratio [OR] 2.4, 95% CI 2.0-2.8), readmission (n=269 versus n=238, adjusted OR
      2.2, 95% CI 1.8-2.6), reoperation (n=80 versus n=93, adjusted OR 1.5, 95% CI 1.2
      2.1), superficial surgical site infection (n=190 versus n=55, adjusted OR 6.8,
      95% CI 5.0-9.2), perioperative transfusion (n=430 versus n=149, adjusted OR 5.9,
      95% CI 4.8-7.1), and death (n=41 vs, n=20, adjusted OR 3.8, 95% CI 2.2-6.6). A
      comprehensive decrease in 30-day morbidity for the treatment of endometrial
      cancer overall was observed from 2008 to 2014 (P<.001), whereas 30-day mortality
      remained stable (P=.24). CONCLUSION: The widespread adoption of minimally
      invasive surgery is associated with substantial decreases in 30-day morbidity,
      readmission, and reoperation for women treated for endometrial cancer in the
      United States.

PMID- 29324599
TI  - Risk Factors, Incidence, and Morbidity Associated With Obstetric Clostridium
      difficile Infection.
AB  - OBJECTIVE: To evaluate the risk factors, incidence, and morbidity associated with
      the diagnosis of obstetric Clostridium difficile infection. METHODS: We performed
      a retrospective cohort study on women admitted for delivery using the Healthcare
      Cost and Utilization Project Nationwide Inpatient Sample from the United States.
      The delivery admission records of pregnant women were reviewed between 1999 and
      2013. After adjusting for demographic and clinical characteristics, we assessed
      risk factors for the diagnosis of C difficile infection using unconditional
      logistic regression. RESULTS: Of the total 13,881,592 births in our cohort, we
      identified 2,757 (0.02%) admissions for delivery complicated by a diagnosis of C
      difficile infection. During the study period, the rate of C difficile infection
      diagnoses among women hospitalized for delivery doubled from 15 (95% CI 11.87
      16.96) to 30 (24.42-31.78) per 100,000 deliveries per year (P<.001). Risk factors
      associated with the diagnosis of C difficile infection included age older than 35
      years, multiple gestations, smoking, Crohn's disease, ulcerative colitis, long
      term antibiotic use, pneumonia, pyelonephritis as well as cesarean or perineal
      wound infection. The diagnosis of C difficile infection in pregnancy was
      associated with a significant increase in maternal death (8.0/1,000 vs 0.1/1,000,
      adjusted odds ratio [OR] 56.8, 95% CI 35.8-90.1). Furthermore, there was an
      increase in sepsis (46.4/1,000 vs 0.6/1,000, adjusted OR 59.1, 95% CI 48.8-71.6),
      paralytic ileus (58.0/1,000 vs 1.5/1,000, adjusted OR 33.1, 95% CI 27.5-39.8),
      venous thromboembolism (38.4/1,000 vs 3.1/1,000, adjusted OR 8.1, 95% CI 6.5
      10.2), and hospital stays greater than 2 weeks (173.0/1,000 vs 6.5,1,000,
      adjusted OR 24.3, 95% CI 21.6-27.4) among pregnant women with C difficile
      infection. CONCLUSION: The diagnosis of C difficile infections in pregnancy has
      increased over the past 15 years and this diagnosis is associated with
      significant maternal morbidity and mortality.

PMID- 29324600
TI  - Reassessing the Duration of the Second Stage of Labor in Relation to Maternal and
      Neonatal Morbidity.
AB  - OBJECTIVE: To assess the morbidity associated with continuing the second-stage
      duration of labor, weighing the probability of spontaneous vaginal birth without
      morbidity compared with birth with serious maternal or neonatal complications.
      METHODS: In a retrospective cohort, we analyzed singleton, vertex births at 36
      weeks of gestation or greater without prior cesarean delivery (n=43,810
      nulliparous and 59,605 multiparous women). We calculated rates of spontaneous
      vaginal birth and composite serious maternal or neonatal complications. Results
      were stratified by parity (nulliparous or multiparous) and epidural status (yes
      or no). Competing risks models were created for 1) spontaneous vaginal birth with
      no morbidity, 2) birth with maternal or neonatal morbidity, and 3) no spontaneous
      vaginal birth and no morbidity, and our main interest was in comparing number 1
      against number 2. RESULTS: Rates of spontaneous vaginal birth without morbidity
      were slightly higher after the first half hour (greater than 0.5-1.0 hours) for
      nulliparous women, after which rates decreased with increasing second-stage
      duration. For multiparous women, rates of spontaneous vaginal birth without
      morbidity decreased with increasing second-stage duration. For illustration, for
      a nulliparous woman with an epidural at 3.0 hours of the second stage of labor
      who extended by another 1.0 hour, her likelihood of delivering by spontaneous
      vaginal birth was 31.4% compared with her likelihood of birth with any serious
      complication in the subsequent hour, which was 7.6%. The percentage of cesarean
      deliveries for nonreassuring fetal heart rate tracing were higher for women
      without compared with women with an epidural. CONCLUSION: Rates of spontaneous
      vaginal birth without serious morbidity steadily decreased for increasing second
      stage duration except for the first half hour for nulliparous women. We did not
      observe an inflection point at a particular hour mark for either spontaneous
      vaginal delivery without morbidity or births with morbidity. Our findings will
      assist in decision-making for extending second-stage duration.

PMID- 29324601
TI  - Potentially Preventable Stillbirth in a Diverse U.S. Cohort.
AB  - OBJECTIVE: To estimate the proportion of potentially preventable stillbirths in
      the United States. METHODS: We conducted a secondary analysis of 512 stillbirths
      with complete evaluation enrolled in the Stillbirth Collaborative Research
      Network from 2006 to 2008. The Stillbirth Collaborative Research Network was a
      multisite, geographically, racially, and ethnically diverse, population-based
      case-control study of stillbirth in the United States. Cases of stillbirth
      underwent standard evaluation that included maternal interview, medical record
      abstraction, biospecimen collection, postmortem examination, placental pathology,
      and clinically recommended evaluation. Each stillbirth was assigned probable and
      possible causes of death using the Initial Causes of Fetal Death algorithm
      system. For this analysis, we defined potentially preventable stillbirths as
      those occurring in nonanomalous fetuses, 24 weeks of gestation or greater, and
      weighing 500 g or greater that were 1) intrapartum, 2) the result of medical
      complications, 3) the result of placental insufficiency, 4) multiple gestation
      (excluding twin-twin transfusion), 5) the result of spontaneous preterm birth, or
      6) the result of hypertensive disorders of pregnancy. RESULTS: Of the 512
      stillbirths included in our cohort, causes of potentially preventable stillbirth
      included placental insufficiency (65 [12.7%]), medical complications of pregnancy
      (31 [6.1%]), hypertensive disorders of pregnancy (20 [3.9%]), preterm labor (16
      [3.1%]), intrapartum (nine [1.8%]), and multiple gestations (four [0.8%]). Twenty
      seven stillbirths fit two or more categories, leaving 114 (22.3%) potentially
      preventable stillbirths. CONCLUSION: Based on our definition, almost one fourth
      of stillbirths are potentially preventable. Given the predominance of placental
      insufficiency among stillbirths, identification and management of placental
      insufficiency may have the most immediate effect on stillbirth reduction.

PMID- 29324602
TI  - Antecedents of Abnormally Invasive Placenta in Primiparous Women: Risk Associated
      With Gynecologic Procedures.
AB  - OBJECTIVE: To evaluate the association between prior invasive gynecologic
      procedures and the risk of subsequent abnormally invasive placenta (ie, placenta
      accreta, increta, and percreta). METHODS: We conducted a population-based data
      linkage study including all primiparous women who delivered in New South Wales,
      Australia, between 2003 and 2012. Data were obtained from linked birth and
      hospital admissions with a minimum lookback period of 2 years. Prior procedures
      invasive of the uterus were considered including gynecologic laparoscopy with
      instrumentation of the uterus; hysteroscopy, including operative hysteroscopy;
      curettage, including suction curettage and surgical termination; and endometrial
      ablation. Modified Poisson regression was used to determine the association
      between the number of prior gynecologic procedures and risk of abnormally
      invasive placenta. RESULTS: Eight hundred fifty-four cases of abnormally invasive
      placenta were identified among 380,775 deliveries included in the study
      (22.4/10,000). In total, 33,296 primiparous women had at least one prior
      procedure (8.7%). Among women with abnormally invasive placenta, 152 (17.8%) had
      undergone at least one procedure compared with 33,144 (8.7%) among women without
      abnormally invasive placenta (P<.01). After adjustment, the relative risk was 1.5
      for one procedure (99% CI 1.1-1.9), 2.7 for two procedures (99% CI 1.7-4.4), and
      5.1 for three or more procedures (99% CI 2.7-9.6). Abnormally invasive placenta
      was also positively associated with maternal age, socioeconomic advantage, mother
      being Australia-born, placenta previa, hypertension, multiple births, use of
      assisted reproductive technology, and female fetal sex. CONCLUSION: Women with a
      history of prior invasive gynecologic procedures were more likely to develop
      abnormally invasive placenta. These insights may be used to inform management of
      pregnancies in women with a history of gynecologic procedures.

PMID- 29324604
TI  - Preterm Birth and Gestational Length in Four Race-Nativity Groups, Including
      Somali Americans.
AB  - OBJECTIVE: To compare preterm birth rates and gestational length in four race
      nativity groups including Somali Americans. METHODS: Using a retrospective cohort
      study design of Ohio birth certificates, we analyzed all singleton births between
      2000 and 2015 from four groups of women categorized as U.S.-born, non-Hispanic
      white (USBW), U.S.-born, non-Hispanic black (USBB), African-born black (ABB,
      primarily of West African birth country), and Somalia-born (SB). An algorithm
      trained on maternal names was used to confirm Somali ethnicity. Gestational
      length was analyzed as completed weeks or aggregated by clinically relevant
      periods. Risk of spontaneous and health care provider-initiated preterm birth was
      calculated in a competing risk model. RESULTS: Births to women in the designated
      groups accounted for 1,960,693 births (USBW n=1,638,219; USBB n=303,028; ABB
      n=10,966, and SB n=8,480). Women in the SB group had a lower preterm birth rate
      (5.9%) compared with women in the USBB (13.0%), ABB (8.4%), and USBW (7.9%)
      groups (P<.001). Women in the SB group had a higher frequency of postterm
      pregnancy (5.8% vs less than 1%, P<.001 for all groups). The lower rate of
      preterm birth in the SB group was unrelated to differences in parity or smoking
      or whether preterm birth was spontaneous or health care provider-initiated. The
      lower rate of preterm birth and tendency for prolonged gestation was attenuated
      in ethnic Somali women born outside Somalia. CONCLUSION: We report a positive
      disparity in preterm birth and a tendency for prolonged gestation for ethnic
      Somali women in Ohio. Etiologic studies in multiethnic cohorts aimed to uncover
      the sociobiological determinants of gestational length may lead to practical
      approaches to reduce prematurity in the general population.

PMID- 29324603
TI  - Pregnancy-Associated Hypertension and Offspring Cardiometabolic Health.
AB  - OBJECTIVE: To evaluate whether pregnancy-associated hypertension (gestational
      hypertension and preeclampsia) was associated with the cardiometabolic health of
      young offspring. METHODS: This was a prospective observational follow-up study
      from 2012 to 2013 of children born to women previously enrolled in a mild
      gestational diabetes mellitus treatment trial or nongestational diabetes mellitus
      observational study. At 5-10 years after birth, children were examined and
      fasting blood samples obtained to determine the following cardiometabolic risk
      factors: blood pressure (BP), high-density lipoprotein cholesterol,
      triglycerides, glucose, homeostatic model assessment of insulin resistance, waist
      circumference, and body mass index (BMI). RESULTS: This analysis included 979
      children evaluated at a median 7 years of age. Twenty-three (2%) were born
      preterm from a hypertensive pregnancy, 73 (7%) were born at term from a
      hypertensive pregnancy, 58 (6%) were born preterm from a normotensive pregnancy,
      and 825 (84%) were born at term from a normotensive pregnancy (reference group).
      After adjusting for confounding factors, mean adjusted systolic BP was
      significantly higher in the children who were born at term to mothers who
      experienced pregnancy-associated hypertension compared with those born at term to
      normotensive mothers (systolic BP of 104 mm Hg, 95% CI 101-106 vs systolic BP of
      99 mm Hg, 95% CI 99-100, P=.001). No other significant differences were observed.
      CONCLUSION: Pregnancy-associated hypertension in women who deliver at term was
      associated with higher systolic BP in the offspring, but not with their measures
      of diastolic BP, BMI, waist circumference, homeostatic model assessment of
      insulin resistance, glucose, or lipids. CLINICAL TRIAL REGISTRATION:
      ClinicalTrials.gov, NCT00069576.

PMID- 29324605
TI  - Estimating the Hospital Delivery Costs Associated With Severe Maternal Morbidity
      in New York City, 2008-2012.
AB  - OBJECTIVE: To quantify the average and total hospital delivery costs associated
      with severe maternal morbidity in excess of nonsevere maternal morbidity
      deliveries over a 5-year period in New York City adjusting for other
      sociodemographic and clinical factors. METHODS: We conducted a population-based
      cross-sectional study using linked birth certificates and hospital discharge data
      for New York City deliveries from 2008 to 2012. Severe maternal morbidity was
      defined using a published algorithm of International Classification of Diseases,
      9 Revision, Clinical Modification disease and procedure codes. Hospital costs
      were estimated by converting hospital charges using factors specific to each year
      and hospital and to each diagnosis. These estimates approximate what it costs the
      hospital to provide services (excluding professional fees) and were used in all
      subsequent analyses. To estimate adjusted mean costs associated with severe
      maternal morbidity, we used multivariable regression models with a log link,
      gamma distribution, robust standard errors, and hospital fixed effects,
      controlling for age, race and ethnicity, neighborhood poverty, primary payer,
      number of deliveries, method of delivery, comorbidities, and year. We used the
      adjusted mean cost to determine the average and total hospital delivery costs
      associated with severe maternal morbidity in excess of nonsevere maternal
      morbidity deliveries from 2008 to 2012. RESULTS: Approximately 2.3% (n=13,502) of
      all New York City delivery hospitalizations were complicated by severe maternal
      morbidity. Compared with nonsevere maternal morbidity deliveries, these
      hospitalizations were clinically complicated, required more and intensive
      clinical services, and had a longer stay in the hospital. The average cost of
      delivery with severe maternal morbidity was $14,442 (95% CI $14,128-14,756),
      compared with $7,289 (95% CI $7,276-7,302) among deliveries without severe
      maternal morbidity. After adjusting for other factors, the difference between
      deliveries with and without severe maternal morbidity remained high ($6,126).
      Over 5 years, this difference resulted in approximately $83 million in total
      excess costs (13,502*$6,126). CONCLUSION: Severe maternal morbidity nearly
      doubled the cost of delivery above and beyond other drivers of cost, resulting in
      tens of millions of excess dollars spent in the health care system in New York
      City. These findings can be used to demonstrate the burden of severe maternal
      morbidity and evaluate the cost-effectiveness of interventions to improve
      maternal health.

PMID- 29324606
TI  - Obstetric Outcomes After Failed Hysteroscopic and Laparoscopic Sterilization
      Procedures.
AB  - OBJECTIVE: To compare obstetric outcomes after failed hysteroscopic and
      laparoscopic sterilization. METHODS: This retrospective cohort study examined
      pregnancy outcomes including live birth, preterm birth, stillbirth, spontaneous
      abortion, therapeutic abortion, ectopic pregnancies, and gestational
      trophoblastic disease using a commercial claims administrative database for the
      years 2007-2013. We used a Z-test to compare pregnancy outcomes per 100 person
      years based on type of sterilization. Cox proportional hazard models controlled
      for patient age, geographic region, urbanicity, comorbidities, and insurance
      type. RESULTS: We evaluated 997 pregnancy outcomes among 817 women from a total
      of 70,115 women with a history of either hysteroscopic sterilization (n=387
      pregnancies/27,724 cases) or laparoscopic sterilization (n=610 pregnancies/42,391
      cases). Women undergoing hysteroscopic sterilization were slightly older than,
      but otherwise similar to, women undergoing laparoscopic sterilization. The most
      common outcome was live birth, which was more likely after hysteroscopic
      sterilization compared with laparoscopic sterilization (adjusted hazard ratio
      1.32, 95% CI 1.09-1.60). The rate of spontaneous abortion was not statistically
      significantly different between the two groups. Therapeutic abortion occurred
      more often after hysteroscopic sterilization (adjusted hazard ratio 1.49, 95% CI
      1.10-2.01), whereas ectopic pregnancies occurred less often (adjusted hazard
      ratio 0.12, 95% CI 0.05-0.29) compared with laparoscopic sterilization.
      CONCLUSION: Hysteroscopic sterilization is associated with higher rates of live
      birth and lower rates of ectopic pregnancy compared with laparoscopic
      sterilization. Spontaneous abortion and preterm birth rates were similar in both
      groups. These data do not support an adverse effect of hysteroscopic
      sterilization on subsequent pregnancy outcomes.

PMID- 29324607
TI  - Effect of Cesarean Delivery on Long-term Risk of Small Bowel Obstruction.
AB  - OBJECTIVE: To evaluate the association of cesarean deliveries on the incidence of
      small bowel obstruction. METHODS: We formed a population-based cohort of all
      women with a first live birth between 1998 and 2007 using the U.K. Clinical
      Practice Research Datalink. Women were followed until 2015, the occurrence of a
      small bowel obstruction, or loss to follow-up. Cesarean delivery was identified
      from the Hospital Episode Statistics and small bowel obstruction events were
      identified using the Classification of Interventions and Procedures and
      International Classification of Diseases, 10th Revision codes. Cox proportional
      hazard models, with cesarean delivery defined as a time-dependent exposure,
      estimated the adjusted hazard ratios and 95% CIs of small bowel obstruction
      associated with cesarean delivery. RESULTS: The cohort included 81,480 women with
      a median follow-up of 8.0 years (range 6 months to 16.6 years), during which 575
      new small bowel obstructions occurred (incidence 9.1/10,000 person-years). Risk
      of small bowel obstruction was higher among women with a cesarean delivery
      compared with women without (16.3 vs 6.4 patients/10,000 person-years, odds ratio
      [OR] 2.54, 95% CI 2.15-3.00). Increasing number of cesarean deliveries was
      associated with an increasing risk of small bowel obstruction (OR 1.61, 95% CI
      1.46-1.78, per additional cesarean delivery). Repeated small bowel obstructions
      were more common among women with a cesarean delivery and the association
      remained when restricting to small bowel obstruction requiring surgical
      management. CONCLUSION: Although rare, small bowel obstructions are increased
      among women who have undergone a cesarean delivery. With increasing rates of
      cesarean deliveries worldwide, small bowel obstructions and related morbidities
      may become a more prevalent women's health concern.

PMID- 29324608
TI  - Quality Assurance Practices in Obstetric Care: A Survey of Hospitals in
      California.
AB  - OBJECTIVE: To assess hospital practices in obstetric quality management
      activities and identify institutional characteristics associated with utilization
      of evidence-supported practices. METHODS: Data for this study came from a
      statewide survey of obstetric hospitals in California regarding their
      organization and delivery of perinatal care. We analyzed responses from 185
      hospitals that completed quality assurance sections of the survey to assess their
      practices in a broad spectrum of quality enhancement activities. The association
      between institutional characteristics and adoption of evidence-supported
      practices (ie, those supported by prior literature or recommended by professional
      organizations as beneficial for improving birth outcome or patient safety) was
      examined using bivariate analysis and appropriate statistical tests. RESULTS:
      Most hospitals regularly audited adherence to written protocols regarding
      critical areas of care; however, 77.7% and 16.8% reported not having written
      guidelines on diagnosis of labor arrest and management of abnormal fetal heart
      rate, respectively. Private nonprofit hospitals were more likely to have a
      written protocol for management of abnormal fetal heart rate (P=.002). One in 10
      hospitals (9.7%) did not regularly review cases with significant morbidity or
      mortality, and only 69.0% regularly tracked indications for cesarean delivery.
      Moreover, 26.3%, 14.3%, and 8.7% of the hospitals reported never performing
      interprofessional simulations for eclampsia, shoulder dystocia, or postpartum
      hemorrhage, respectively. Teaching status was associated with more frequent
      simulations in these three areas (P<=.04 for all), while larger volume was
      associated with more frequent simulations for eclampsia (P=.04). CONCLUSION:
      Hospitals in California engage in a wide range of practices to assure or improve
      quality of obstetric care, but substantial variation in practice exists among
      hospitals. There is opportunity for improvement in adoption of evidence-supported
      practices.

PMID- 29324609
TI  - Outcomes of Planned Compared With Urgent Deliveries Using a Multidisciplinary
      Team Approach for Morbidly Adherent Placenta.
AB  - OBJECTIVE: To compare outcomes between planned and urgent cesarean hysterectomy
      for morbidly adherent placenta managed by a multidisciplinary team. METHODS: This
      is a retrospective case-control study of women with singleton pregnancies with
      antenatally suspected and pathologically confirmed morbidly adherent placenta who
      underwent cesarean hysterectomy between January 1, 2011, and February 30, 2017.
      Timing of delivery was classified as either planned (delivery at 34-35 weeks of
      gestation) or urgent (need for urgent delivery as a result of uterine
      contractions, bleeding, or both). The primary outcome variable was composite
      maternal morbidity. Logistic regression analysis was used to evaluate risk
      factors for urgent delivery. RESULTS: One hundred thirty patients underwent
      hysterectomy. Sixty (46.2%) required urgent delivery. Composite maternal
      morbidity was identified in 34 (56.7%) of the urgent and 26 (37.1%) of the
      planned deliveries (P=.03). Fewer units of red blood cells and fresh frozen
      plasma were transfused in the planned delivery group (red blood cells, median
      interquartile range 3 [0-8] versus 1 [0-4], P=.02; fresh frozen plasma, median
      interquartile range 1 [0-2] versus 0 [0-0], P=.001). Rates of low Apgar score and
      respiratory distress syndrome were higher in the urgent compared with the planned
      delivery group (5-minute Apgar score less than 7, 34 [59.6%] versus 14 [23.3%],
      P<.01; respiratory distress syndrome, 34 [61.8%] versus 16 [27.1%], P<.01). A
      history of two or more prior cesarean deliveries was an independent predictor of
      urgent delivery (adjusted odds ratio 11.4, 95% CI 1.8-71.1). CONCLUSION: Women
      with morbidly adherent placenta requiring urgent delivery have a worse outcome
      than women with planned delivery. Women with morbidly adherent placenta and two
      or more prior cesarean deliveries are at increased risk for urgent delivery. In
      such women, scheduling delivery before the standard 34- to 35-week timeframe may
      be reasonable.

PMID- 29324610
TI  - Risk Factors for the Development of Obstetric Anal Sphincter Injuries in Modern
      Obstetric Practice.
AB  - OBJECTIVE: To characterize the rate of obstetric anal sphincter injuries and
      identify key risk factors of obstetric anal sphincter injuries, including
      duration of the second stage of labor. METHODS: This retrospective cohort study
      included all singleton, term, cephalic vaginal deliveries within Kaiser
      Permanente Northern California between January 2013 and December 2014 (N=22,741).
      Incidence of obstetric anal sphincter injuries, defined as third- or fourth
      degree perineal lacerations, was the primary outcome. Multiple logistic
      regression models were conducted to identify obstetric anal sphincter injury risk
      factors and high-risk subpopulations. RESULTS: The overall incidence rate of
      obstetric anal sphincter injuries was 4.9% (3.6% of women who delivered
      spontaneously vs 24.0% of women who had a vacuum-assisted vaginal delivery,
      P<.001, CI 18.1-22.6%). In bivariate and multivariate analyses, obstetric anal
      sphincter injury incidence was higher among women with second stage of labor
      longer than 2 hours, Asian race, nulliparity, vaginal birth after cesarean
      delivery, episiotomy, and vacuum delivery. Women with a vacuum-assisted vaginal
      delivery had four times the odds of obstetric anal sphincter injury (adjusted
      odds ratio [OR] 4.23, 95% CI 3.59-4.98) and those whose second stage of labor
      lasted at least 180 minutes vs less than 60 minutes had three times the odds of
      incurring obstetric anal sphincter injury (adjusted OR 3.20, 95% CI 2.62-3.89).
      CONCLUSION: Vacuum-assisted vaginal delivery conferred the highest odds of
      obstetric anal sphincter injury followed by prolonged duration of the second
      stage of labor, particularly among certain subpopulations. Understanding these
      risk factors and their complex interactions can inform antepartum and intrapartum
      decision-making with the goal of reducing obstetric anal sphincter injury
      incidence.

PMID- 29324611
TI  - Equal Pay for Equal Work in Academic Obstetrics and Gynecology.
AB  - The most compelling data suggest women in academic obstetrics and gynecology earn
      approximately $36,000 less than male colleagues per year in regression models
      correcting for commonly cited explanatory variables. Although residual
      confounding may exist, academic departments in the United States should consider
      rigorous examination of their own internal metrics around salary to ensure gender
      neutral compensation, commonly referred to as equal pay for equal work.

PMID- 29324612
TI  - Third-Trimester Maternal Vaccination Against Pertussis and Pertussis Antibody
      Concentrations.
AB  - OBJECTIVE: To compare pertussis antibody concentrations in maternal venous serum
      (at the time of delivery) and umbilical cord arterial serum among women
      vaccinated with the tetanus toxoid, reduced diphtheria toxoid, and acellular
      pertussis (Tdap) vaccine from either 27-30 6/7 weeks of gestation or from 31-35
      6/7 weeks of gestation. METHODS: We conducted a prospective cohort study of
      pregnant women divided into two groups based on when Tdap was administered: 27-30
      6/7 weeks of gestation and 31-35 6/7 weeks of gestation. Paired maternal and
      umbilical cord samples were obtained at the time of delivery to determine
      immunoglobulin G (IgG) concentrations to pertussis toxin and pertactin. RESULTS:
      Eighty-eight pregnant women were enrolled. Cord serum pertussis toxin IgG
      concentrations were approximately twice maternal serum pertussis toxin IgG
      concentrations (91.6 vs 48.6 enzyme-linked immunoassay [ELISA] units/mL, P<.01)
      and were significantly correlated (Pearson correlation coefficient=0.85, P<.01).
      There was no significant difference in maternal serum pertussis toxin IgG
      concentrations (48.6 vs 48.6 ELISA units/mL, P=.99), cord serum pertussis toxin
      IgG concentrations (92.1 vs 90.7 ELISA units/mL, P=.95), and cord serum pertactin
      IgG concentrations (798 vs 730 international units/mL, P=.73) between the two
      groups. Furthermore, there was no correlation between time from vaccination to
      delivery and these three parameters. Cord serum pertussis toxin IgG
      concentrations were greater than 10 ELISA units/mL (ie, in the protective range)
      in 87% and 97% of those vaccinated from 27-30 6/7 weeks of gestation and from 31
      35 6/7 weeks of gestation, respectively (P=.13). CONCLUSION: Maternal vaccination
      against pertussis between 27 and 36 weeks of gestation was associated with a high
      percentage of newborns with antibody concentrations conferring protection and did
      not vary by gestational age at vaccination.

PMID- 29324614
TI  - Subsequent Pregnancy Outcomes in Patients With Peripartum Cardiomyopathy.
AB  - OBJECTIVE: To describe cardiac and obstetric outcomes in subsequent pregnancies
      of patients with peripartum cardiomyopathy and to report demographic and clinical
      characteristics of index pregnancies. METHODS: We conducted a retrospective
      cohort study of all pregnant patients with prior peripartum cardiomyopathy seen
      at the Mayo Clinic from January 2000 through March 2017. Maternal and neonatal
      outcome data of index and all subsequent pregnancies were abstracted, and all
      echocardiography examinations were individually reviewed. RESULTS: Twenty-five
      patients with prior peripartum cardiomyopathy were included; all except one had
      recovered left ventricular (LV) function (LV ejection fraction 50% or greater)
      before the subsequent pregnancy. Forty-three subsequent pregnancies were
      identified: six (14.0%) miscarriages, four (9.3%) terminations, and 33 (76.7%)
      live births. The rate of peripartum cardiomyopathy relapse was 20.9%; median LV
      ejection fraction nadir in patients with relapse was 43% (range 35-45%). None had
      LV ejection fraction decline to the level of their index pregnancy. No cardiac
      arrests or deaths were observed, and all patients with relapse recovered LV
      function. Median gestational age at delivery for all live births in subsequent
      pregnancies was 39.0 weeks (range 36 6/7-41 3/7 weeks). CONCLUSION: Patients with
      a history of peripartum cardiomyopathy who recover LV function are at risk for a
      transient minor decrease in LV ejection fraction during future pregnancies, but
      obstetric and neonatal outcomes are often favorable.

PMID- 29324613
TI  - Racial Disparities in Adverse Pregnancy Outcomes and Psychosocial Stress.
AB  - OBJECTIVE: To assess the relationships between self-reported psychosocial stress
      and preterm birth, hypertensive disease of pregnancy, and small-for-gestational
      age (SGA) birth and to assess the extent to which these relationships account for
      racial and ethnic disparities in these adverse outcomes. METHODS: Self-reported
      measures of psychosocial stress (perceived stress, depression, racism, anxiety,
      resilience, and social support) were collected during pregnancy among a racially
      and ethnically diverse cohort of women enrolled in a prospective observational
      study of nulliparous women with singleton pregnancies, from eight clinical sites
      across the United States, between October 2010 and May 2014. The associations of
      preterm birth, hypertensive disease of pregnancy, and SGA birth with the self
      reported measures of psychosocial stress as well as with race and ethnicity were
      evaluated. RESULTS: The study included 9,470 women (60.4% non-Hispanic white,
      13.8% non-Hispanic black, 16.7% Hispanic, 4.0% Asian, and 5.0% other). Non
      Hispanic black women were significantly more likely to experience any preterm
      birth, hypertensive disease of pregnancy, and SGA birth than were non-Hispanic
      white women (12.2% vs 8.0%, 16.7% vs 13.4%, and 17.2% vs 8.6%, respectively;
      P<.05 for all). After adjusting for potentially confounding factors, including
      the six different psychosocial factors singly and in combination, non-Hispanic
      black women continued to be at greater risk of any preterm birth and SGA birth
      compared with non-Hispanic white women. CONCLUSION: Among a large and
      geographically diverse cohort of nulliparous women with singleton gestations, non
      Hispanic black women are most likely to experience preterm birth, hypertensive
      disease of pregnancy, and SGA birth. These disparities were not materially
      altered for preterm birth or SGA birth by adjustment for demographic differences
      and did not appear to be explained by differences in self-reported psychosocial
      factors.

PMID- 29324615
TI  - Associations Between Childbirth and Urinary Incontinence After Midurethral Sling
      Surgery.
AB  - OBJECTIVE: To assess whether subsequent childbirths affect the outcomes of
      midurethral sling surgery with regard to stress urinary incontinence (SUI).
      METHODS: In this population-based cohort study, we used the validated Swedish
      nationwide health care registers (the Patient Register and the Medical Birth
      Register) to identify women with a delivery after midurethral sling surgery
      (n=207, study group). From the same registers we then randomly identified a
      control group who had no deliveries after their midurethral sling procedure
      (n=521, control group). The women in the control group were matched to the women
      in the study group by age and year of surgery. The Urogenital Distress Inventory
      and the Incontinence Impact Questionnaire were sent out to the study population.
      Symptomatic SUI was defined as the primary outcome. Secondary outcomes included
      the total Urogenital Distress Inventory score, Urogenital Distress Inventory
      subscale scores, and Incontinence Impact Questionnaire scores. RESULTS: A total
      of 728 women were eligible for the study. The response rate was 74%; 163 in the
      study group (64 with vaginal delivery and 95 with cesarean delivery) and 374
      women in the control group were included in the analysis. The rate of SUI
      (primary outcome) was 36 of 163 (22%) in the study group and 63 of 374 (17%) in
      the control group. In a multivariate regression analysis of the primary outcome,
      we found no significant difference between the groups (odds ratio [OR] 1.2, 95%
      CI 0.7-2.0). Vaginal childbirth after midurethral sling surgery did not increase
      the risk of SUI compared with cesarean delivery (22% vs 22%, OR 0.6, 95% CI 0.2
      1.4). There were no significant differences in Urogenital Distress Inventory and
      Incontinence Impact Questionnaire scores between any of the groups. CONCLUSION:
      Childbirth after a midurethral sling procedure is not associated with an
      increased risk of patient-reported SUI, and continence status is not affected by
      the mode of a subsequent delivery.

PMID- 29324616
TI  - In Search of More Sleep.

PMID- 29324617
TI  - Quality Assurance and Improvement Tools: How to Choose Wisely.

PMID- 29324618
TI  - Connect the Dots-February 2018.

PMID- 29324619
TI  - What Is New in Global Women's Health? (Part 2): Best Articles From the Past Year.
AB  - This month we focus on current research in women's global health. Drs. Stuart and
      Ramsey discuss five recent publications, which are concluded with a "bottom line"
      that is a take-home message. A complete reference for each can be found in on
      this page along with direct links to abstracts.

PMID- 29324620
TI  - Diagnosis and Treatment of Vulvar Dermatoses.
AB  - Vulvar symptoms of pain, dyspareunia, and pruritus are common and may
      significantly affect a woman's sense of well-being and sexual function. Despite
      this, vulvar symptoms are often underreported by women. When identified, however,
      vulvovaginal symptoms should be addressed by health care providers to optimize
      care. The evaluation of patients with vulvovaginal complaints begins with a
      thorough history and physical examination. Biopsy is indicated when concern
      exists for malignancy or the diagnosis is uncertain. Treatment, if possible,
      should be evidence-based, although for many vulvar disorders including vulvar
      dermatoses, treatment is based on limited evidence and anecdotal experience.
      Although many vulvar dermatoses represent chronic conditions and thus cannot be
      simply cured, control is possible for the majority of women. Patient education
      regarding vulvar hygiene and skin care is the foundation for optimal management
      of inflammatory vulvar dermatoses. These conditions may be triggered or worsened
      by aggressive hygiene. Additionally, patients should be counseled regarding the
      need for individually tailored long-term maintenance to achieve optimal outcomes.

PMID- 29324621
TI  - Immediate Delivery Compared With Expectant Management in Late Preterm Prelabor
      Rupture of Membranes: An Individual Participant Data Meta-analysis.
AB  - OBJECTIVE: To compare the effects of immediate delivery an expectant management
      among women whose pregnancies were complicated by preterm prelabor rupture of
      membranes (PROM) in the late preterm period (from 34 0/7 weeks until 36 6/7 weeks
      of gestation). DATA SOURCES: PubMed, Scopus, ClinicalTrials.gov, EMBASE, and the
      Cochrane Central Register of Controlled Trials were searched from inception until
      December 2016. METHODS OF STUDY SELECTION: We included all randomized controlled
      trials with individual participant data reporting on late preterm PROM with
      randomization to immediate delivery or expectant management. The primary outcome
      was a composite of adverse neonatal outcomes: probable or definitive neonatal
      sepsis, necrotizing enterocolitis, respiratory distress syndrome, stillbirth, or
      neonatal death. TABULATION, INTEGRATION AND RESULTS: Of eight eligible trials
      (total n=3,203 mothers), three (2,563 mothers, 2,572 neonates) had individual
      participant data available. The composite adverse neonatal outcome occurred in
      9.6% of neonates in the immediate delivery group and 8.3% in the expectant
      management group (relative risk [RR] 1.20, 95% CI 0.94-1.55). Neonatal sepsis
      rates were 2.6% and 3.5%, respectively (RR 0.74, 95% CI 0.47-1.15). Neonates in
      the immediate delivery group were more likely to be diagnosed with respiratory
      distress syndrome (RR 1.47, 95% CI 1.10-1.97), and to be admitted to the neonatal
      intensive care unit or special care nursery (RR 1.17, 95% CI 1.11-1.23) and had
      longer admissions. Mothers randomized to immediate delivery were less likely to
      have an antepartum hemorrhage (RR 0.57, 95% CI 0.34-0.95) or chorioamnionitis (RR
      0.21, 95% CI 0.13-0.35), but more likely to undergo cesarean delivery (RR 1.26,
      95% CI 1.08-1.47). CONCLUSION: In women with late preterm PROM, immediate
      delivery and expectant management resulted in comparable rates of the composite
      of adverse neonatal outcomes. Effects on individual secondary maternal and
      neonatal outcomes were mixed. SYSTEMATIC REVIEW REGISTRATION: PROSPERO,
      42016032972.

PMID- 29324622
TI  - Frostbite: Don't be left out in the cold.

PMID- 29324623
TI  - New Drugs 2018, part 1.

PMID- 29324624
TI  - INTRAVITREAL AFLIBERCEPT IN THE TREATMENT OF POLYPOIDAL CHOROIDAL VASCULOPATHY
      ASSOCIATED WITH MORNING GLORY SYNDROME.
AB  - PURPOSE: To describe an unusual case of polypoidal choroidal vasculopathy
      secondary to morning glory syndrome successfully treated with three aflibercept
      intravitreal injections. METHODS: Case report. RESULTS: A 68-year-old white man
      presented with a 2-month history of diminished vision of his left eye. Fundus
      examination showed a morning glory syndrome disk anomaly with some perimacular
      subretinal hemorrhages and lipid depositions. Fundus autofluorescence,
      fluorescein and green indocyanine angiography, spectral domain optical coherence
      tomography, and optical coherence tomography angiography were performed and
      confirmed the presence of a juxtapapillary polypoidal choroidal vasculopathy with
      intraretinal and subretinal fluid. Patient underwent 3 monthly intravitreal
      injections of aflibercept and at 4-month follow-up visit, multimodal imaging
      findings did not show any kind of neovascular lesion activity. CONCLUSION:
      Polypoidal choroidal vasculopathy can occur in morning glory syndrome and it can
      be successfully treated with anti-vascular endothelial growth factor intravitreal
      injections of aflibercept.

PMID- 29324626
TI  - Vascular Effects of Adrenomedullin and the Anti-Adrenomedullin Antibody
      Adrecizumab in Sepsis.
AB  - Sepsis remains a major scientific and medical challenge, for which, apart from
      significant refinements in supportive therapy, treatment has barely changed over
      the last few decades. During sepsis, both vascular tone and vascular integrity
      are compromised, and contribute to the development of shock. The free circulating
      peptide adrenomedullin (ADM) is involved in the regulation of the endothelial
      barrier function and tone of blood vessels. Several animal studies have shown
      that ADM administration improves outcome of sepsis. However, in higher dosages,
      ADM administration may cause hypotension, limiting its clinical applicability.
      Moreover, ADM has a very short half-life and easily adheres to surfaces, further
      hampering its clinical use. The non-neutralizing anti-ADM antibody Adrecizumab
      (HAM8101) which causes a long-lasting increase of plasma ADM has shown promising
      results in animal models of systemic inflammation and sepsis; it reduced
      inflammation, attenuated vascular leakage, and improved hemodynamics, kidney
      function, and survival. Combined with an excellent safety profile derived from
      animal and phase I human studies, Adrecizumab represents a promising candidate
      drug for the adjunctive treatment of sepsis. In this review, we first provide a
      brief overview of the currently available data on the role of adrenomedullin in
      sepsis and describe its effects on endothelial barrier function and vasodilation.
      Furthermore, we provide a novel hypothesis concerning the mechanisms of action
      through which Adrecizumab may exert its beneficial effects in sepsis.

PMID- 29324625
TI  - Comparison of the ARK Immunoassay With High-Performance Liquid Chromatography
      With Ultraviolet Detection for Therapeutic Drug Monitoring of Linezolid.
AB  - BACKGROUND: An enzymatic immunoassay is under development by ARK Diagnostics, Inc
      for the quantification of plasma concentrations of linezolid (LZD). In this
      study, the authors aimed to assess the performance of this immunoassay using a
      validated high-performance liquid chromatography (HPLC) ultraviolet method as
      reference. METHODS: Within- and between-day in vitro inaccuracy and imprecision
      of the ARK LZD assay were firstly tested using spiked quality controls (QC)
      provided by the kit manufacturer. Subsequently, the performance of the
      immunoassay was verified in vivo by analyzing 170 trough LZD plasma samples from
      patients on antibiotic therapy. RESULTS: Imprecision of the spiked QCs resulted
      in every instance less than 7.0% and the inaccuracy ranged from -1.5% to 6.6%.
      The linear correlation between the 2 methods was documented by the Pearson
      analysis of plasma samples from patients on LZD therapy (coefficient = 0.9619).
      By Bland-Altman comparison, 8.2% of the patient samples resulted out of the
      limits ranging from -27.0% to +33.5%, with most of them having LZD concentrations
      exceeding 10 mg/L. CONCLUSIONS: Acceptable analytical performance of the ARK LZD
      immunoassay has been demonstrated both with spiked QC and patients' samples,
      making it a viable alternative to HPLC for the therapeutic drug monitoring of LZD
      in clinical practice in laboratory hospitals that do not have HPLC equipment.

PMID- 29324627
TI  - Effects of the Humanized Anti-Adrenomedullin Antibody Adrecizumab (HAM8101) on
      Vascular Barrier Function and Survival in Rodent Models of Systemic Inflammation
      and Sepsis.
AB  - PURPOSE: Adrenomedullin (ADM) is an important regulator of endothelial barrier
      function during sepsis. Administration of a murine antibody targeted against the
      N-terminus of ADM (HAM1101) resulted in improved outcome in models of murine
      sepsis. We studied the effects of a humanized form of this antibody (HAM8101,
      also known as Adrecizumab) on vascular barrier dysfunction and survival in rodent
      models of systemic inflammation and sepsis. METHODS: Rats (n=48) received
      different dosages of HAM8101 or placebo (n = 8 per group), directly followed by
      administration of lipopolysaccharide (5 mg/kg). Twenty-four hours later, Evans
      Blue dye was administered to assess vascular leakage in kidney and liver tissue.
      Furthermore, mice (n = 24) were administered different dosages of HAM8101 or
      placebo (n = 6 per group), immediately followed by cecal ligation and puncture
      (CLP). Eighteen hours later, albumin, vascular endothelial growth factor (VEGF),
      and angiopoietin-1 were analyzed in the kidney. Finally, effects of single and
      repeated dose administration of HAM1101, HAM8101 and placebo on survival were
      assessed in CLP-induced murine sepsis (n = 60, n = 10 per group). RESULTS:
      Dosages of 0.1 and 2.5 mg/kg HAM8101 attenuated renal albumin leakage in
      endotoxemic rats. Dosages of 0.1, 2.0, and 20 mg/kg HAM8101 reduced renal
      concentrations of albumin and the detrimental protein VEGF in septic mice,
      whereas concentrations of the protective protein angiopoietin-1 were augmented.
      Both single and repeated administration of both HAM1101 and HAM8101 resulted in
      improved survival during murine sepsis. CONCLUSIONS: Pretreatment with the
      humanized anti-ADM antibody HAM8101 improved vascular barrier function and
      survival in rodent models of systemic inflammation and sepsis.

PMID- 29324628
TI  - Ulinastatin Protects Against LPS-Induced Acute Lung Injury By Attenuating TLR4/NF
      kappaB Pathway Activation and Reducing Inflammatory Mediators.
AB  - Acute lung injury (ALI) and its severe form, acute respiratory distress syndrome,
      remain the leading causes of morbidity and mortality in intensive care units.
      Ulinastatin (UTI), a serine protease inhibitor, possesses anti-inflammatory
      properties and has been suggested to modulate lipopolysaccharide (LPS)-induced
      sepsis; thus, it is now widely used in the treatment of pancreatitis, sepsis, and
      septic shock. Toll-like receptor 4 (TLR4), an essential LPS signaling receptor,
      plays a critical role in the activation of innate immunity. The aim of this study
      was to investigate whether UTI alleviates ALI by attenuating TLR4 expression and
      to explore the underlying molecular mechanisms involved. Male C56BL/6 mice were
      administered UTI intravenously 1 h before and 6 h after exposure to LPS by
      intratracheal instillation. Human lung epithelial (BEAS-2B) cells were incubated
      with LPS in the presence or absence of UTI. An enzyme-linked immunosorbent assay
      was used to detect levels of inflammatory cytokines. Western blot analysis was
      performed to detect changes in TLR4 expression and nuclear factor-kappaB (NF
      kappaB) activation. UTI significantly protected animals from LPS-induced ALI,
      decreasing the lung wet/dry weight ratio, ALI score, total cells, neutrophils,
      macrophages, myeloperoxidase activity, and malondialdehyde content, factors
      associated with lung histological damage. UTI treatment also markedly attenuated
      levels of TLR4 and other proinflammatory cytokines. Furthermore, UTI
      significantly attenuated LPS-induced increases in TLR4 protein expression and NF
      kappaB activation in lung tissues. Similarly, UTI markedly attenuated TLR4
      expression and NF-kappaB activation in LPS-stimulated BEAS-2B cells. These
      findings indicate that UTI ameliorates LPS-induced ALI by attenuating the TLR4/NF
      kappaB pathway activation.

PMID- 29324629
TI  - Susceptibility of Neisseria gonorrhoeae to Gentamicin-Gonococcal Isolate
      Surveillance Project, 2015-2016.
AB  - The gentamicin minimum inhibitory concentrations (MICs) of Neisseria gonorrhoeae
      isolates were determined. Seventy-three percent of isolates demonstrated an MIC
      range of 8 to 16 MUg/mL, and 27% demonstrated an MIC of 4 MUg/mL or less.
      Significant associations between gentamicin MIC and resistance or reduced
      susceptibility to other antimicrobials were found.

PMID- 29324630
TI  - Perforated Meckel Diverticulum: A Rare Cause of Acute Abdomen in Children.
AB  - Meckel diverticulum (MD) is the most common congenital anomaly of the
      gastrointestinal tract and the most common cause of gastrointestinal bleeding in
      children. Although it usually follows the rule of 2's, exceptions to this rule
      are reported in the literature. Often asymptomatic, MD is commonly an incidental
      finding during surgical interventions. When symptomatic, the most common
      presentation of this condition is painless rectal bleeding. A myriad of other
      nonspecific symptoms are however possible, especially in adults, thus making this
      diagnosis difficult. Meckel diverticulum has been reported to mimic other
      abdominal pathologies like appendicitis, inflammatory bowel disease, and
      pancreatitis to name a few.We report a patient with acute abdomen in whom the
      more common causes of acute abdomen were ruled out and a diagnosis of MD was
      established on exploratory laparoscopy, only after he developed perforation. This
      report emphasizes the need for maintaining a high index of suspicion towards a
      possibility of a complicated MD in patients presenting with an acute abdomen,
      once other causes of acute abdomen are ruled out.

PMID- 29324631
TI  - Pediatric Appendicitis: Association of Chief Complaint With Missed Appendicitis.
AB  - OBJECTIVES: We evaluated the association between the emergency department (ED)
      triage chief complaint and rate of missed appendicitis in children. METHODS: We
      performed a retrospective chart review of patients who presented to a pediatric
      ED and were diagnosed with appendicitis over 5 years (July 1, 2009 to June 30,
      2014). We reviewed the medical record for any additional ED visits in the 7 days
      preceding the diagnosis of appendicitis. Triage chief complaints were classified
      as "suggestive of appendicitis" (abdominal pain, right lower quadrant pain, or
      rule out appendicitis) or "nonspecific" (fever, vomiting, dehydration, etc). We
      evaluated the association between triage chief complaint and missed diagnosis of
      appendicitis. RESULTS: We reviewed 1680 patients with appendicitis. In 67 (4%)
      cases, patients had at least 1 additional ED visit during the week preceding the
      diagnosis of appendicitis. When comparing those diagnosed with appendicitis at
      their initial ED visit to those diagnosed after multiple visits, we found no
      difference in age (9.9 vs 10.1 years, P = 0.665), sex (55.7% vs 49.3% male, P =
      0.291), white blood cell count (14.4 vs 12.3 * 103/L, P = 0.115), or presence of
      fever (19.9% vs 19.4%, P = 0.920). Of patients with a triage chief complaint that
      was suggestive of appendicitis, 3.8% were missed on their initial ED visit versus
      8.8% of those with a nonspecific triage chief complaint (odds ratio, 2.46; 95%
      confidence interval, 1.1-5.6). CONCLUSIONS: A triage chief complaint less
      suggestive of appendicitis was associated with a higher rate of missed
      appendicitis in a pediatric ED. Our findings further confirm the potential impact
      of anchoring bias by a triage chief complaint when attempting to diagnose
      appendicitis.

PMID- 29324632
TI  - Chair Lift Falls and Injuries in Children.
AB  - OBJECTIVE: The objective of this study was to compare demographic injury and
      treatment characteristics of hospitalized pediatric cases of falls from chair
      lifts to cases of other ski and snowboarding injuries and identify potential
      interventions for preventing falls from chair lifts. METHODS: Retrospective query
      of the trauma registry of Utah's only pediatric trauma center for children
      younger than 18 years requiring hospitalization for a ski or snowboarding injury
      from November 2004 to February 2014. RESULTS: There were 443 cases of
      hospitalized ski and snowboarding injuries during the study period. Twenty-nine
      cases (7%) fell from height while riding a chair lift. Children falling from
      chair lifts were more likely to be younger (6.9 years vs 12.1, P < 0.0001),
      female (41% vs 20%, P < 0.01), and elicit trauma team activation (72% vs 34%, P =
      <0.0001) but were less frequently treated in the operating room (14 vs 24%, P =
      0.02) than children with other ski and snowboarding injuries. There were no
      differences in mortality, injury severity score, length of hospital stay, or
      airway intubation outside the operating room. When stated (11/29 cases), mean
      estimated height of fall from lift was 26 feet. The most common body region in
      chair lift falls with a significant injury (abbreviated injury scale, >=3) was
      lower extremity (4/29, all femur fractures). Patient age discriminated chair lift
      falls well (area under the receiver operating characteristic curve, 0.87) with
      age of 7 years and below predicting chair lift fall with a sensitivity of 76% and
      a specificity of 91%. CONCLUSIONS: Injuries requiring hospitalization after falls
      from chair lifts occur at regulated facilities and are more common in younger
      female children when compared with other ski and snowboarding injuries.
      Interventions for reducing falls from chair lifts may be most effective applied
      to children 7 years and younger.

PMID- 29324633
TI  - Pediatric Electric Bicycle Injuries: The Experience of a Large Urban Tertiary
      Care Pediatric Hospital.
AB  - BACKGROUND: Electric bicycles (E-bikes) are one of a wide range of light electric
      vehicles that provide convenient local transportation and attractive recreational
      opportunities. The aim of this study was to report E-bike-related injuries in
      children presenting to a trauma center. METHODS: Retrospective observational
      study, from December 2014 to November 2015, which included all pediatrics
      patients admitted to the emergency department with an injury related to E-bike
      use, was performed. RESULTS: A total of 97 E-bike injuries presented to the
      emergency department during this period. Mean age of E-bikers was 13.7 years
      (range, 7.5-16 years). Injuries to the head and the upper and the lower
      extremities were the most common. Thirteen patients (15%) were admitted, and 4
      underwent surgery. CONCLUSIONS: Children are mainly injured as riders when using
      E-bikes. There is a need for regulation regarding the use of E-bikes to enhance
      the safety of both bikers and other road and pavement users.

PMID- 29324634
TI  - Point-of-Care Ultrasound Evaluation of Severe Renal Trauma in an Adolescent.
AB  - Traumatic renal injuries are more common in pediatrics because of the relatively
      larger size of the kidneys in the pediatric patient. Although computerized
      tomography remains the criterion standard for the initial evaluation of blunt
      renal trauma, there is evidence that renal ultrasound may serve a role in
      postinjury surveillance. Here, we present a case in which point-of-care
      ultrasound was used to image severe blunt renal trauma in a 17-year-old
      adolescent boy. In this case, point-of-care ultrasound identified severely
      distorted renal parenchyma after a grade 5 renal laceration was identified on
      computerized tomography scan.

PMID- 29324635
TI  - Diagnostic Value of Serum Urokinase-Type Plasminogen Activator Receptor in
      Children With Acute Appendicitis.
AB  - OBJECTIVES: Acute appendicitis (AA) is the most common surgical emergency in
      children. The accurate and timely diagnosis of AA in children can be challenging,
      and delayed diagnosis rates have been reported to range from 5.9% to 27.6%.
      Although combining clinical history and repeated physical examination with
      laboratory tests and radiographic imaging modalities help reach the diagnosis,
      novel biomarkers can support the surgeons' decision as well. The aims of this
      study were to evaluate a new plasma marker, urokinase-type plasminogen activator
      receptor (uPAR), to improve diagnostic accuracy in AA patients, and to determine
      a cutoff value of uPAR, which can safely include/exclude the diagnosis of AA.
      METHODS: We conducted a prospective study of children who underwent surgery for
      AA. Patients were categorized into the following 3 groups: group 1, controls
      consisted of 32 healthy volunteers; group 2, patients underwent surgery for
      nonperforated AA (n = 35); and group 3, patients underwent surgery for perforated
      AA (n = 21). Blood was sampled from group 1 at the admission and from group 2 and
      3 before appendectomy. Serum uPAR, white blood cell count, absolute neutrophil
      count (ANC), and C-reactive protein concentrations were measured. RESULTS:
      Urokinase-type plasminogen activator receptor, ANC, and white blood cell count
      values were significantly higher in group 2 and 3 than group 1, but there was no
      significant difference between group 2 and 3. C-reactive protein values were
      significantly higher only in group 3 than other groups. The cutoff value for uPAR
      is 2.2 ng/mL with sensitivity of 85.7% and specificity of 84.3% and ANC is 5900
      cells/mm with sensitivity of 91.1% and specificity of 96.9% to diagnose
      appendicitis. The specificity was 81.3% and sensitivity was raised to 98.2% when
      evaluated together. CONCLUSIONS: The incorporation of uPAR count and ANC could be
      a strong predictor of AA in children.

PMID- 29324637
TI  - The Chemistry of Alliums.
AB  - Physiologically active sulfur-containing compounds produced by Allium spp. have
      long fascinated chemists, biochemists, and biologists.[...].

PMID- 29324636
TI  - Simple Sequence Repeat (SSR) Genetic Linkage Map of D Genome Diploid Cotton
      Derived from an Interspecific Cross between Gossypium davidsonii and Gossypium
      klotzschianum.
AB  - The challenge in tetraploid cotton cultivars is the narrow genetic base and
      therefore, the bottleneck is how to obtain interspecific hybrids and introduce
      the germplasm directly from wild cotton to elite cultivars. Construction of
      genetic maps has provided insight into understanding the genome structure,
      interrelationships between organisms in relation to evolution, and discovery of
      genes that carry important agronomic traits in plants. In this study, we
      generated an interspecific hybrid between two wild diploid cottons, Gossypium
      davidsonii and Gossypium klotzschianum, and genotyped 188 F2:3 populations in
      order to develop a genetic map. We screened 12,560 SWU Simple Sequence Repeat
      (SSR) primers and obtained 1000 polymorphic markers which accounted for only 8%.
      A total of 928 polymorphic primers were successfully scored and only 728 were
      effectively linked across the 13 chromosomes, but with an asymmetrical
      distribution. The map length was 1480.23 cM, with an average length of 2.182 cM
      between adjacent markers. A high percentage of the markers on the map developed,
      and for the physical map of G. raimondii, exhibited highly significant
      collinearity, with two types of duplication. High level of segregation distortion
      was observed. A total of 27 key genes were identified with diverse roles in plant
      hormone signaling, development, and defense reactions. The achievement of
      developing the F2:3 population and its genetic map constructions may be a
      landmark in establishing a new tool for the genetic improvement of cultivars from
      wild plants in cotton. Our map had an increased recombination length compared to
      other maps developed from other D genome cotton species.

PMID- 29324638
TI  - Molecular Research on Drug Induced Liver Injury.
AB  - Drugs may cause liver injury in a few susceptible individuals, but the molecular
      events that lead to this idiosyncratic, largely dose-independent and non
      predictable drug-induced liver injury (DILI) are mostly unknown, since animal
      models to explore the pathogenetic mechanisms of human idiosyncratic DILI are not
      yet reliable.[...].

PMID- 29324639
TI  - Depopulation of Caged Layer Hens with a Compressed Air Foam System.
AB  - During the 2014-2015 US highly pathogenic avian influenza (HPAI) outbreak, 50.4
      million commercial layers and turkeys were affected, resulting in economic losses
      of $3.3 billion. Rapid depopulation of infected poultry is vital to contain and
      eradicate reportable diseases like HPAI. The hypothesis of the experiment was
      that a compressed air foam (CAF) system may be used as an alternative to carbon
      dioxide (CO2) inhalation for depopulating caged layer hens. The objective of this
      study was to evaluate corticosterone (CORT) and time to cessation of movement
      (COM) of hens subjected to CAF, CO2 inhalation, and negative control (NEG)
      treatments. In Experiment 1, two independent trials were conducted using young
      and spent hens. Experiment 1 consisted of five treatments: NEG, CO2 added to a
      chamber, a CO2 pre-charged chamber, CAF in cages, and CAF in a chamber. In
      Experiment 2, only spent hens were randomly assigned to three treatments: CAF in
      cages, CO2 added to a chamber, and aspirated foam. Serum CORT levels of young
      hens were not significantly different among the CAF in cages, CAF in a chamber,
      NEG control, and CO2 inhalation treatments. However, spent hens subjected to the
      CAF in a chamber had significantly higher CORT levels than birds in the rest of
      the treatments. Times to COM of spent hens subjected to CAF in cages and
      aspirated foam were significantly greater than of birds exposed to the CO2 in a
      chamber treatment. These data suggest that applying CAF in cages is a viable
      alternative for layer hen depopulation during a reportable disease outbreak.

PMID- 29324641
TI  - Genetic Algorithm-Based Motion Estimation Method using Orientations and EMGs for
      Robot Controls.
AB  - Demand for interactive wearable devices is rapidly increasing with the
      development of smart devices. To accurately utilize wearable devices for remote
      robot controls, limited data should be analyzed and utilized efficiently. For
      example, the motions by a wearable device, called Myo device, can be estimated by
      measuring its orientation, and calculating a Bayesian probability based on these
      orientation data. Given that Myo device can measure various types of data, the
      accuracy of its motion estimation can be increased by utilizing these additional
      types of data. This paper proposes a motion estimation method based on weighted
      Bayesian probability and concurrently measured data, orientations and
      electromyograms (EMG). The most probable motion among estimated is treated as a
      final estimated motion. Thus, recognition accuracy can be improved when compared
      to the traditional methods that employ only a single type of data. In our
      experiments, seven subjects perform five predefined motions. When orientation is
      measured by the traditional methods, the sum of the motion estimation errors is
      37.3%; likewise, when only EMG data are used, the error in motion estimation by
      the proposed method was also 37.3%. The proposed combined method has an error of
      25%. Therefore, the proposed method reduces motion estimation errors by 12%.

PMID- 29324640
TI  - Heart Rate Variability Frequency Domain Alterations among Healthy Nurses Exposed
      to Prolonged Work Stress.
AB  - The deregulation of the autonomic nervous system assessed through the heart rate
      variability (HRV) analysis is a promising pathway linking work stress and
      cardiovascular diseases. We aim to investigate the associations between HRV High
      Frequency (HF) and Low Frequency (LF) powers and work stress in a sample of 36
      healthy nurses. Perceived work stress was assessed twice one year apart, using
      the Job Content and Effort Reward Imbalance questionnaires. This allows to
      classify nurses in three exposure groups: "prolonged high stress" (PHS), "recent
      high stress" (RHS) and "stable low stress" (SLS). A 24-h ECG monitoring was later
      performed during a working day (WD) and a subsequent resting day (RD).
      Statistically significantly lower (p < 0.02) HF and LF means were found in PHS
      and RHS nurses during the working periods. In the subsequent resting periods, HF
      means showed increases over time in the RHS (beta = +0.41, p < 0.05), but not in
      PHS nurses. LF means did not show any substantial increases in the resting
      periods, in the PHS group with geometric means lower when compared to SLS, in the
      non-working and resting periods. Our study evidences that both prolonged and
      recent perceived high work stress were associated with a reduction of HF and LF
      powers during work. In addition, prolonged stress was associated with a lack of
      recovery during not-working and resting periods.

PMID- 29324642
TI  - Antibacterial and Antioxidant Capacities and Attenuation of Lipid Accumulation in
      3T3-L1 Adipocytes by Low-Molecular-Weight Fucoidans Prepared from Compressional
      Puffing-Pretreated Sargassum Crassifolium.
AB  - In this study, we extracted fucoidan from compressional-puffing-pretreated
      Sargassum crassifolium by hot water. The crude extract of fucoidan (SC) was
      degraded by various degradation reagents and four low-molecular-weight (LMW)
      fucoidans, namely SCO (degradation by hydrogen peroxide), SCA (degradation by
      ascorbic acid), SCOA (degradation by hydrogen peroxide + ascorbic acid), and SCH
      (degradation by hydrogen chloride) were obtained. The degradation reagents
      studied could effectively degrade fucoidan into LMW fucoidans, as revealed by
      intrinsic viscosity, agarose gel electrophoresis, and molecular weight analyses.
      These LMW fucoidans had higher uronic acid content and sulfate content than those
      of SC. It was found that SCOA exhibited antibacterial activity. All LMW fucoidans
      showed antioxidant activities as revealed by DPPH (2,2-diphenyl-1
      picrylhydrazyl), ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)
      diammonium salt), and FRAP (ferric reducing antioxidant power) methods.
      Biological experiments showed that SC and SCOA had relatively high activity for
      the reversal of H2O2-induced cell death in 3T3-L1 adipocytes, and SCOA showed the
      highest effect on attenuation of lipid accumulation in 3T3-L1 adipocytes.
      Therefore, for the LMW fucoidans tested, SCOA showed antibacterial activity and
      had a high fucose content, high sulfate content, high activity for the reversal
      of H2O2-induced cell death, and a marked effect on attenuation of lipid
      accumulation. It can thus be recommended as a natural and safe antibacterial and
      anti-adipogenic agent for food, cosmetic, and nutraceutical applications.

PMID- 29324643
TI  - Nutritional Status of Bariatric Surgery Candidates.
AB  - Obesity is a global epidemic affecting populations globally. Bariatric surgery is
      an effective treatment for morbid obesity, and has increased dramatically.
      Bariatric surgery candidates frequently have pre-existing nutritional
      deficiencies that might exacerbate post-surgery. To provide better health care
      management pre- and post-bariatric surgery, it is imperative to establish the
      nutritional status of prospective patients before surgery. The aim of this study
      was to assess and provide baseline data on the nutritional status of bariatric
      candidates. A retrospective study was conducted on obese patients who underwent
      bariatric surgery from 2008 to 2015. The medical records of 1538 patients were
      reviewed for this study. Pre-operatively, the most commonly observed vitamin
      deficiencies were Vitamin D (76%) and Vitamin B12 (16%). Anemia and iron status
      parameters were low in a considerable number of patients before surgery, as
      follows: hemoglobin 20%, mean corpuscular volume (MCV) 48%, ferritin 28%, serum
      iron 51%, and transferrin saturation 60%. Albumin and transferrin were found to
      be low in 10% and 9% of the patients, respectively, prior to surgery. In addition
      to deficiencies, a great number of patients had hypervitaminosis pre-operatively.
      Excess levels of Vitamin B6 (24%) was the most remarkable. The findings in this
      study advocate a close monitoring and tailored supplementation pre- and post
      bariatric surgery.

PMID- 29324645
TI  - Esophageal Web in a Down Syndrome Infant-A Rare Case Report.
AB  - We describe the rare case of an infant with trisomy 21 who presented with
      recurrent vomiting and aspiration pneumonia and a failure to thrive. Infants with
      Down's syndrome have been known to have various problems in the gastrointestinal
      tract. In the esophagus, what have been described are dysmotility,
      gastroesophageal reflux and strictures. This infant on evaluation was found to
      have an esophageal web and simple endoscopic dilatation relieved the infant of
      her symptoms. No similar case has been reported in literature.

PMID- 29324644
TI  - Nanocomposite of Half-Fin Anchovy Hydrolysates/Zinc Oxide Nanoparticles Exhibits
      Actual Non-Toxicity and Regulates Intestinal Microbiota, Short-Chain Fatty Acids
      Production and Oxidative Status in Mice.
AB  - The nanocomposite of half-fin anchovy hydrolysates (HAHp) and zinc oxide
      nanoparticles (ZnO NPs) (named as HAHp(3.0)/ZnO NPs) demonstrated increased
      antibacterial activity compared to either HAHp(3.0) or ZnO NPs as per our
      previous studies. Also, reactive oxygen species (ROS) formation was detected in
      Escherichia coli cells after treatment with HAHp(3.0)/ZnO NPs. The aim of the
      present study was to evaluate the acute toxicity of this nanocomposite and to
      investigate its effect on intestinal microbiota composition, short-chain fatty
      acids (SCFAs) production, and oxidative status in healthy mice. The limit test
      studies show that this nanoparticle is non-toxic at the doses tested. The
      administration of HAHp(3.0)/ZnO NPs, daily dose of 1.0 g/kg body weight for 14
      days, increased the number of goblet cells in jejunum. High-throughput 16S
      ribosomal RNA gene sequencing of fecal samples revealed that HAHp(3.0)/ZnO NPs
      increased Firmicutes and reduced Bacteriodetes abundances in female mice.
      Furthermore, the microbiota for probiotic-type bacteria, including Lactobacillus
      and Bifidobacterium, and SCFAs-producing bacteria in the Clostridia class, e.g.,
      Lachnospiraceae_unclassified and Lachnospiraceae_UCG-001, were enriched in the
      feces of female mice. Increases of SCFAs, especially statistically increased
      propionic and butyric acids, indicated the up-regulated anti-inflammatory
      activity of HAHp(3.0)/ZnO NPs. Additionally, some positive responses in liver,
      like markedly increased glutathione and decreased malonaldehyde contents,
      indicated the improved oxidative status. Therefore, our results suggest that
      HAHp(3.0)/ZnO NPs could have potential applications as a safe regulator of
      intestinal microbiota or also can be used as an antioxidant used in food
      products.

PMID- 29324646
TI  - Analysis of Microcystins in Cyanobacterial Blooms from Freshwater Bodies in
      England.
AB  - Cyanobacterial blooms in freshwater bodies in England are currently monitored
      reactively, with samples containing more than 20,000 cells/mL of potentially
      toxin-producing species by light microscopy resulting in action by the water body
      owner. Whilst significantly reducing the risk of microcystin exposure, there is
      little data describing the levels of these toxins present in cyanobacterial
      blooms. This study focused on the quantitative LC-MS/MS analysis of microcystins
      in freshwater samples, collected across England during 2016 and found to contain
      potentially toxin-producing cyanobacteria. More than 50% of samples contained
      quantifiable concentrations of microcystins, with approximately 13% exceeding the
      WHO medium health threshold of 20 MUg/L. Toxic samples were confirmed over a nine
      month period, with a clear increase in toxins during late summer, but with no
      apparent geographical patterns. No statistical relationships were found between
      total toxin concentrations and environmental parameters. Complex toxin profiles
      were determined and profile clusters were unrelated to cyanobacterial species,
      although a dominance of MC-RR was determined in water samples from sites
      associated with lower rainfall. 100% of samples with toxins above the 20 MUg/L
      limit contained cell densities above 20,000 cells/mL or cyanobacterial scum,
      showing the current regime is suitable for public health. Conversely, with only
      18% of cell density threshold samples having total microcystins above 20 MUg/L,
      there is the potential for reactive water closures to unnecessarily impact upon
      the socio-economics of the local population. In the future, routine analysis of
      bloom samples by LC-MS/MS would provide a beneficial confirmatory approach to the
      current microscopic assessment, aiding both public health and the needs of water
      users and industry.

PMID- 29324647
TI  - Mapping Early, Middle and Late Rice Extent Using Sentinel-1A and Landsat-8 Data
      in the Poyang Lake Plain, China.
AB  - Areas and spatial distribution information of paddy rice are important for
      managing food security, water use, and climate change. However, there are many
      difficulties in mapping paddy rice, especially mapping multi-season paddy rice in
      rainy regions, including differences in phenology, the influence of weather, and
      farmland fragmentation. To resolve these problems, a novel multi-season paddy
      rice mapping approach based on Sentinel-1A and Landsat-8 data is proposed. First,
      Sentinel-1A data were enhanced based on the fact that the backscattering
      coefficient of paddy rice varies according to its growth stage. Second, cropland
      information was enhanced based on the fact that the NDVI of cropland in winter is
      lower than that in the growing season. Then, paddy rice and cropland areas were
      extracted using a K-Means unsupervised classifier with enhanced images. Third, to
      further improve the paddy rice classification accuracy, cropland information was
      utilized to optimize distribution of paddy rice by the fact that paddy rice must
      be planted in cropland. Classification accuracy was validated based on ground
      data from 25 field survey quadrats measuring 600 m * 600 m. The results show
      that: multi-season paddy rice planting areas effectively was extracted by the
      method and adjusted early rice area of 1630.84 km2, adjusted middle rice area of
      556.21 km2, and adjusted late rice area of 3138.37 km2. The overall accuracy was
      98.10%, with a kappa coefficient of 0.94.

PMID- 29324648
TI  - LSPR and Interferometric Sensor Modalities Combined Using a Double-Clad Optical
      Fiber.
AB  - We report on characterization of an optical fiber-based multi-parameter sensor
      concept combining localized surface plasmon resonance (LSPR) signal and
      interferometric sensing using a double-clad optical fiber. The sensor consists of
      a micro-Fabry-Perot in the form of a hemispherical stimuli-responsive hydrogel
      with immobilized gold nanorods on the facet of a cleaved double-clad optical
      fiber. The swelling degree of the hydrogel is measured interferometrically using
      the single-mode inner core, while the LSPR signal is measured using the multi
      mode inner cladding. The quality of the interferometric signal is comparable to
      previous work on hydrogel micro-Fabry-Perot sensors despite having gold nanorods
      immobilized in the hydrogel. We characterize the effect of hydrogel swelling and
      variation of bulk solution refractive index on the LSPR peak wavelength. The
      results show that pH-induced hydrogel swelling causes only weak redshifts of the
      longitudinal LSPR mode, while increased bulk refractive index using glycerol and
      sucrose causes large blueshifts. The redshifts are likely due to reduced plasmon
      coupling of the side-by-side configuration as the interparticle distance
      increases with increasing swelling. The blueshifts with increasing bulk
      refractive index are likely due to alteration of the surface electronic structure
      of the gold nanorods donated by the anionic polymer network and glycerol or
      sucrose solutions. The recombination of biotin-streptavidin on gold nanorods in
      hydrogel showed a 7.6 nm redshift of the longitudinal LSPR. The LSPR response of
      biotin-streptavidin recombination is due to the change in local refractive index
      (RI), which is possible to discriminate from the LSPR response due to changes in
      bulk RI. In spite of the large LSPR shifts due to bulk refractive index, we show,
      using biotin-functionalized gold nanorods binding to streptavidin, that LSPR
      signal from gold nanorods embedded in the anionic hydrogel can be used for label
      free biosensing. These results demonstrate the utility of immobilizing gold
      nanorods in a hydrogel on a double-clad optical fiber-end facet to obtain multi
      parameter sensing.

PMID- 29324649
TI  - Machine Learning Methods for Analysis of Metabolic Data and Metabolic Pathway
      Modeling.
AB  - Machine learning uses experimental data to optimize clustering or classification
      of samples or features, or to develop, augment or verify models that can be used
      to predict behavior or properties of systems. It is expected that machine
      learning will help provide actionable knowledge from a variety of big data
      including metabolomics data, as well as results of metabolism models. A variety
      of machine learning methods has been applied in bioinformatics and metabolism
      analyses including self-organizing maps, support vector machines, the kernel
      machine, Bayesian networks or fuzzy logic. To a lesser extent, machine learning
      has also been utilized to take advantage of the increasing availability of
      genomics and metabolomics data for the optimization of metabolic network models
      and their analysis. In this context, machine learning has aided the development
      of metabolic networks, the calculation of parameters for stoichiometric and
      kinetic models, as well as the analysis of major features in the model for the
      optimal application of bioreactors. Examples of this very interesting, albeit
      highly complex, application of machine learning for metabolism modeling will be
      the primary focus of this review presenting several different types of
      applications for model optimization, parameter determination or system analysis
      using models, as well as the utilization of several different types of machine
      learning technologies.

PMID- 29324650
TI  - Update on the Impact of Omega 3 Fatty Acids on Inflammation, Insulin Resistance
      and Sarcopenia: A Review.
AB  - Elderly and patients affected by chronic diseases face a high risk of muscle loss
      and impaired physical function. Omega 3 fatty acids (FA) attenuate inflammation
      and age-associated muscle loss, prevent systemic insulin resistance and improve
      plasma lipids, potentially impacting on sarcopenia. This paper aims to review
      recent randomized clinical studies assessing the effects a chronic omega 3 FA
      supplementation on inflammatory and metabolic profile during conditions
      characterized by sarcopenia (aging, insulin resistance, type 2 diabetes, chronic
      renal failure). A comprehensive search of three online databases was performed to
      identify eligible trials published between 2012 and 2017. A total of 36 studies
      met inclusion criteria. Omega 3 FA yielded mixed results on plasma triglycerides
      in the elderly and no effects in renal patients. No changes in systemic insulin
      resistance were observed. Inflammation markers did not benefit from omega 3 FA in
      insulin resistant and in renal subjects while decreasing in obese and elderly.
      Muscle related parameters improved in elderly and in renal patients. In
      conclusion, in aging- and in chronic disease-associated sarcopenia omega 3 FA are
      promising independently of associated anabolic stimuli or of anti-inflammatory
      effects. The evidence for improved glucose metabolism in insulin resistant and in
      chronic inflammatory states is less solid.

PMID- 29324651
TI  - Incidence, Microbiological Profile and Risk Factors of Healthcare-Associated
      Infections in Intensive Care Units: A 10 Year Observation in a Provincial
      Hospital in Southern Poland.
AB  - Healthcare-associated infections (HAIs) occurring in patients treated in an
      intensive care unit (ICU) are serious complications in the treatment process.
      Aetiological factors of these infections can have an impact on treatment effects,
      treatment duration and mortality. The aim of the study was to determine the
      prevalence and microbiological profile of HAIs in patients hospitalized in an ICU
      over a span of 10 years. The active surveillance method was used to detect HAIs
      in adult patients who spent over 48 h in a general ICU ward located in southern
      Poland between 2007 and 2016. The study was conducted in compliance with the
      methodology recommended by the Healthcare-associated Infections Surveillance
      Network (HAI-Net) of the European Centre for Disease Prevention and Control
      (ECDC). During the 10 years of the study, 1849 patients hospitalized in an ICU
      for a total of 17,599 days acquired 510 with overall HAIs rates of 27.6% and
      29.0% infections per 1000 ICU days. Intubation-associated pneumonia (IAP) posed
      the greatest risk (15.2 per 1000 ventilator days), followed by CLA-BSI (8.0 per
      1000 catheter days) and CA-UTI (3.0 per 1000 catheter days). The most common
      isolated microorganism was Acinetobacter baumannii (25%) followed by Coagulaase
      negativ staphylococci (15%), Escherichia coli (9%), Pseudomonas aeruginosa (8%),
      Klebsiella pneumoniae (7%), Candida albicans (6%). Acinetobacter baumannii in 87%
      and were classified as extensive-drug resistant (XDR). In summary, in ICU
      patients pneumonia and bloodstream infections were the most frequently found.
      Acinetobacter baumannii strains were most often isolated from clinical materials
      taken from HAI patients and showed resistance to many groups of antibiotics. A
      trend of increasing resistance of Acinetobacter baumannii to carbapenems was
      observed.

PMID- 29324653
TI  - Surgical Dynamometer to Simultaneously Measure the Tension Forces and the
      Distance between Wound Edges during the Closure of a Laparotomy.
AB  - The closure of the abdominal wall after making a laparotomy is a major challenge
      for surgeons, since a significant percentage of closures fail and incisional
      hernias rise. The suture has to withstand the forces required to close the
      incision, while not hindering the adequate wound healing progression. Currently,
      there is no surgical measuring device that could be used to determine the
      required closing forces, which can be very different depending on the patient.
      This paper presents a dynamometer to measure the tension forces to be applied
      while closing a surgical incision, and it simultaneously measures the distance
      between wound edges. It is a compass-like instrument. A mechanism between the two
      legs incorporates a load cell, whose signal is read by an electronic device that
      computes the values of the tension forces between wound edges. An angular
      position sensor at the pin joint between legs provides the distance between both
      sides of the incision. Measuring capabilities of the instrument prototype were
      verified at the laboratory. Thereafter, its functionality was demonstrated in
      experimental surgery tests. Therefore, the instrument could be very useful in
      clinical applications, assisting personalized surgical techniques.

PMID- 29324655
TI  - Evaluation of an Accelerated Workflow for Surveillance of ESBL (CTX-M)-Producing
      Escherichia coli Using Amplicon-Based Next-Generation Sequencing and Automated
      Analysis.
AB  - Outbreak management of extended spectrum beta-lactamase (ESBL)-producing
      pathogens requires rapid and accurate diagnosis. However, conventional screening
      is slow and labor-intensive. The vast majority of the screened samples are
      negative and detection of non-outbreak-related resistant micro-organisms often
      complicates outbreak management. In a CTX-M-15-producing Escherichia coli
      outbreak, 149 fecal samples and rectal eSwabs were collected by a cross-sectional
      survey in a Dutch nursing home. Samples were processed by routine diagnostic
      methods. Retrospectively, ESBL-producing bacteria and resistance genes were
      detected directly from eSwab medium by an accelerated workflow without prior
      enrichment cultures by an amplicon-based next-generation sequencing (NGS) method,
      and culture. A total of 27 (18.1%) samples were positive in either test.
      Sensitivity for CTX-M detection was 96.3% for the phenotypic method and 85.2% for
      the NGS method, and the specificity was 100% for both methods, as confirmed by
      micro-array. This resulted in a positive predictive value (PPV) of 100% for both
      methods, and a negative predictive value (NPV) of 99.2% and 96.8% for the
      phenotypic method and the NGS method, respectively. Time to result was four days
      and 14 h for the phenotypic method and the NGS method, respectively. In
      conclusion, the sensitivity without enrichment shows promising results for
      further use of amplicon-based NGS for screening during outbreaks.

PMID- 29324654
TI  - Zinc Status and Autoimmunity: A Systematic Review and Meta-Analysis.
AB  - Zinc is an essential trace element for living organisms and their biological
      processes. Zinc plays a key role in more than 300 enzymes and it is involved in
      cell communication, proliferation, differentiation and survival. Zinc plays also
      a role in regulating the immune system with implications in pathologies where
      zinc deficiency and inflammation are observed. In order to examine the
      experimental evidence reported in the literature regarding zinc levels in the
      body of patients with autoimmune disorders compared to control individuals, a
      systematic review and meta-analysis were performed. From 26,095 articles
      identified by literature search, only 179 of them were considered potentially
      relevant for our study and then examined. Of the 179 articles, only 62 satisfied
      the inclusion criteria. Particularly for Fixed Model, Zn concentration in both
      serum (mean effect = -1.19; confidence interval: -1.26 to -1.11) and plasma (mean
      effect = -3.97; confidence interval: -4.08 to -3.87) samples of autoimmune
      disease patients was significantly lower than in controls. The data presented in
      our work, although very heterogeneous in the manner of collecting and
      investigating samples, have proved to be extremely consistent in witnessing a
      deficiency of zinc in serum and plasma of patients compared to controls.

PMID- 29324657
TI  - alpha-Glucosidase Inhibition and Antibacterial Activity of Secondary Metabolites
      from the Ecuadorian Species Clinopodium taxifolium (Kunth) Govaerts.
AB  - The phytochemical investigation of both volatile and fixed metabolites of
      Clinopodium taxifolium (Kunth) Govaerts (Lamiaceae) was performed for the first
      time. It allowed the isolation and characterization of the essential oil and six
      known compounds: carvacrol (1), squalane (2), uvaol (3), erythrodiol (4), ursolic
      acid (5), and salvigenin (6). Their structures were identified and characterized
      by Nuclear Magnetic Resonance (NMR) and Gas Chromatography coupled to Mass
      Spectroscopy (GC-MS), and corroborated by literature. The essential oil of the
      leaves was obtained by hydrodistillation in two different periods and analyzed by
      GC-MS and GC coupled to Flame Ionization Detector (GC-FID). A total of 54
      compounds were detected, of which 42 were identified (including trace
      constituents). The major constituents were carvacrol methyl ether (18.9-23.2%),
      carvacrol (13.8-16.3%) and, carvacryl acetate (11.4-4.8%). The antibacterial
      activities were determined as Minimum Inhibition Concentration (MIC) against
      Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, Klebsiella
      pneumoniae, Proteus vulgaris, Pseudomonas aeruginosa and Micrococcus luteus. The
      hexane and methanol extracts exhibited activity only against Klebsiella
      pneumoniae (250 and 500 MUg/mL respectively), while the ethyl acetate extract was
      inactive. The hypoglycemic activity was evaluated by the in vitro inhibition of
      alpha-glucosidase. The ethyl acetate (EtOAc) extract showed strong inhibitory
      activity with IC50 = 24.88 ug/mL, however methanolic and hexanic extracts showed
      weak activity. As a pure compound, only ursolic acid showed a strong inhibitory
      activity, with IC50 = 72.71 MUM.

PMID- 29324658
TI  - Study of the Microstructure and Cracking Mechanisms of Hastelloy X Produced by
      Laser Powder Bed Fusion.
AB  - Hastelloy X (HX) is a Ni-based superalloy which suffers from high crack
      susceptibility during the laser powder bed fusion (LPBF) process. In this work,
      the microstructure of as-built HX samples was rigorously investigated to
      understand the main mechanisms leading to crack formation. The microstructural
      features of as-built HX samples consisted of very fine dendrite architectures
      with dimensions typically less than 1 um, coupled with the formation of sub
      micrometric carbides, the largest ones were mainly distributed along the
      interdendritic regions and grain boundaries. From the microstructural analyses,
      it appeared that the formation of intergranular carbides provided weaker zones,
      which combined with high thermal residual stresses resulted in hot cracks
      formation along the grain boundaries. The carbides were extracted from the
      austenitic matrix and characterized by combining different techniques, showing
      the formation of various types of Mo-rich carbides, classified as M6C, M12C and
      MnCm type. The first two types of carbides are typically found in HX alloy,
      whereas the last one is a metastable carbide probably generated by the very high
      cooling rates of the process.

PMID- 29324652
TI  - Food Addiction and Binge Eating: Lessons Learned from Animal Models.
AB  - The feeding process is required for basic life, influenced by environment cues
      and tightly regulated according to demands of the internal milieu by regulatory
      brain circuits. Although eating behaviour cannot be considered "addictive" under
      normal circumstances, people can become "addicted" to this behaviour, similarly
      to how some people are addicted to drugs. The symptoms, cravings and causes of
      "eating addiction" are remarkably similar to those experienced by drug addicts,
      and both drug-seeking behaviour as eating addiction share the same neural
      pathways. However, while the drug addiction process has been highly
      characterised, eating addiction is a nascent field. In fact, there is still a
      great controversy over the concept of "food addiction". This review aims to
      summarize the most relevant animal models of "eating addictive behaviour",
      emphasising binge eating disorder, that could help us to understand the
      neurobiological mechanisms hidden under this behaviour, and to improve the
      psychotherapy and pharmacological treatment in patients suffering from these
      pathologies.

PMID- 29324660
TI  - In Vitro Bioavailability Study of an Antiviral Compound Enisamium Iodide.
AB  - An investigation into the biopharmaceutics classification and a study of the in
      vitro bioavailability (permeability and solubility) of the antiviral compound
      enisamium iodide (4-(benzylcarbamoyl)-1-methylpyridinium iodide) were carried
      out. The solubility of enisamium iodide was determined in four different buffers.
      Apparent intestinal permeability (Papp) of enisamium iodide was assessed using
      human colon carcinoma (Caco-2) cells at three concentrations. The solubility of
      enisamium iodide in four buffer solutions from pH 1.2 to 7.5 is about 60 mg/mL at
      25  degrees C, and ranges from 130 to 150 mg/mL at 37  degrees C, depending on
      the pH. Based on these results, enisamium iodide can be classified as highly
      soluble. Enisamium iodide demonstrated low permeability in Caco-2 experiments in
      all tested concentrations of 10-100 MUM with permeability coefficients between
      0.2 * 10-6 cm s-1 and 0.3 * 10-6 cm s-1. These results indicate that enisamium
      iodide belongs to class III of the Biopharmaceutics Classification System (BCS)
      due to its high solubility and low permeability. The bioavailability of enisamium
      iodide needs to be confirmed in animal and human studies.

PMID- 29324662
TI  - Aryl Hydrocarbon Receptor Antagonists Mitigate the Effects of Dioxin on Critical
      Cellular Functions in Differentiating Human Osteoblast-Like Cells.
AB  - The inhibition of bone healing in humans is a well-established effect associated
      with cigarette smoking, but the underlying mechanisms are still unclear. Recent
      work using animal cell lines have implicated the aryl hydrocarbon receptor (AhR)
      as a mediator of the anti-osteogenic effects of cigarette smoke, but the
      complexity of cigarette smoke mixtures makes understanding the mechanisms of
      action a major challenge. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD, dioxin) is a
      high-affinity AhR ligand that is frequently used to investigate biological
      processes impacted by AhR activation. Since there are dozens of AhR ligands
      present in cigarette smoke, we utilized dioxin as a prototype ligand to activate
      the receptor and explore its effects on pro-osteogenic biomarkers and other
      factors critical to osteogenesis using a human osteoblast-like cell line. We also
      explored the capacity for AhR antagonists to protect against dioxin action in
      this context. We found dioxin to inhibit osteogenic differentiation, whereas co
      treatment with various AhR antagonists protected against dioxin action. Dioxin
      also negatively impacted cell adhesion with a corresponding reduction in the
      expression of integrin and cadherin proteins, which are known to be involved in
      this process. Similarly, the dioxin-mediated inhibition of cell migration
      correlated with reduced expression of the chemokine receptor CXCR4 and its
      ligand, CXCL12, and co-treatment with antagonists restored migratory capacity.
      Our results suggest that AhR activation may play a role in the bone regenerative
      response in humans exposed to AhR activators, such as those present in cigarette
      smoke. Given the similarity of our results using a human cell line to previous
      work done in murine cells, animal models may yield data relevant to the human
      setting. In addition, the AhR may represent a potential therapeutic target for
      orthopedic patients who smoke cigarettes, or those who are exposed to secondhand
      smoke or other environmental sources of aryl hydrocarbons.

PMID- 29324661
TI  - Protein Activity of the Fusarium fujikuroi Rhodopsins CarO and OpsA and Their
      Relation to Fungus-Plant Interaction.
AB  - Fungi possess diverse photosensory proteins that allow them to perceive different
      light wavelengths and to adapt to changing light conditions in their environment.
      The biological and physiological roles of the green light-sensing rhodopsins in
      fungi are not yet resolved. The rice plant pathogen Fusarium fujikuroi exhibits
      two different rhodopsins, CarO and OpsA. CarO was previously characterized as a
      light-driven proton pump. We further analyzed the pumping behavior of CarO by
      patch-clamp experiments. Our data show that CarO pumping activity is strongly
      augmented in the presence of the plant hormone indole-3-acetic acid and in sodium
      acetate, in a dose-dependent manner under slightly acidic conditions. By
      contrast, under these and other tested conditions, the Neurospora rhodopsin (NR)
      like rhodopsin OpsA did not exhibit any pump activity. Basic local alignment
      search tool (BLAST) searches in the genomes of ascomycetes revealed the
      occurrence of rhodopsin-encoding genes mainly in phyto-associated or
      phytopathogenic fungi, suggesting a possible correlation of the presence of
      rhodopsins with fungal ecology. In accordance, rice plants infected with a CarO
      deficient F. fujikuroi strain showed more severe bakanae symptoms than the
      reference strain, indicating a potential role of the CarO rhodopsin in the
      regulation of plant infection by this fungus.

PMID- 29324665
TI  - Genome-Wide Methylation Patterns in Androgen-Independent Prostate Cancer Cells: A
      Comprehensive Analysis Combining MeDIP-Bisulfite, RNA, and microRNA Sequencing
      Data.
AB  - This study aimed to investigate the mechanisms underlying the development of the
      androgen-independent phenotype in prostate cancer. Methylation patterns were
      detected in androgen-independent and androgen-dependent lymph node carcinoma of
      the prostate (LNCaP) prostate carcinoma cells based on methylated DNA
      immunoprecipitation-bisulfite sequencing data and differentially methylated
      regions (DMRs) were identified. Differentially expressed genes (DEGs) and micro
      RNAs (miRNAs) with DMRs (named MDEGs and MDEmiRNAs) were identified by combining
      transcriptome and methylation data, and transcription factor (TF)-DEGs with DMRs
      in promoter (PMDEGs) and MDEmiRNA-MDEGs networks were constructed. Furthermore, a
      time-course analysis of gene transcription during androgen deprivation was
      performed based on microarray data and DMRs, MDEGs, and DEmiRNAs were validated.
      In total, 18,447 DMRs, 3369 MDEGs, 850 PMDEGs, and 1 MDEmiRNA (miR-429) were
      identified. A TF-target network (94 PMDEGs and 5 TFs) and a miRNA-target network
      (172 MDEGs and miR-429) were constructed. Based on the time-course analysis of
      genes in the networks, NEDD4L and PBX3 were targeted by SOX5, while GNAQ, ANLN,
      and KIF11 were targeted by miR-429. The expression levels of these genes and miR
      429 were confirmed by quantitative real-time polymerase chain reaction.
      Additionally, 109 DMRs were confirmed using additional public datasets. The
      regulatory pathways SOX5-NEDD4L/PBX3, miR429-GNAQ/ANLN-RHOA, and miR429-ANLN
      KIF11 may participate in the progression of the androgen-independent phenotype in
      prostate cancer.

PMID- 29324668
TI  - Effect of Ultrasonic Extraction on Production and Structural Changes of C
      Phycocyanin from Marine Spirulina maxima.
AB  - This work first showed that very high amounts of phycocyanins, such as 11.3 mg/mL
      C-phycocyanin (C-PC), 3.1 mg/mL allophycocyanin (APC), and 0.8 mg/mL
      phycoerythrin (PE), can be obtained using an ultrasonic extraction process (UE)
      with a 60 kHz frequency and 3 h of process time at 25  degrees C, without any
      other pretreatments. These yields were higher than those from most conventional
      water extractions at 4  degrees C for 24 h (Control condition) or at 25  degrees
      C for 24 h (WE), namely, 9.8 and 5.7 mg/mL C-PC, 2.3 and 1.2 mg/mL APC, and 0.7
      and 0.3 mg/mL PE, respectively. These yields were also shown to be even higher
      than yields from other reported data. Structural changes in C-PC in the extracts
      were also found for the first time, according to extraction conditions, showing
      that the total concentration of C-PC and of the alpha-subunit of C-PC in the UE
      were much higher than in the WE, with little difference in the amount of beta
      subunit of C-PC in the UE or WE. It was also shown that the structural changes in
      C-PC in the WE decreased both antioxidant and anti-inflammation activities-29.83%
      vs. 32.09% of alpha,alpha-diphenyl-beta-picrylhydrazyl (DPPH) scavenging activity
      and 8.21 vs. 7.25 uM of NO production for the WE and UE, respectively-while the
      UE, with similar patterns to standard C-PC, showed very high biological effects,
      which may suggest that the biologically active part is the alpha-subunit of C-PC,
      not the beta-subunit.

PMID- 29324666
TI  - Mapping the Schizophrenia Genes by Neuroimaging: The Opportunities and the
      Challenges.
AB  - Schizophrenia (SZ) is a heritable brain disease originating from a complex
      interaction of genetic and environmental factors. The genes underpinning the
      neurobiology of SZ are largely unknown but recent data suggest strong evidence
      for genetic variations, such as single nucleotide polymorphisms, making the brain
      vulnerable to the risk of SZ. Structural and functional brain mapping of these
      genetic variations are essential for the development of agents and tools for
      better diagnosis, treatment and prevention of SZ. Addressing this, neuroimaging
      methods in combination with genetic analysis have been increasingly used for
      almost 20 years. So-called imaging genetics, the opportunities of this approach
      along with its limitations for SZ research will be outlined in this invited
      paper. While the problems such as reproducibility, genetic effect size,
      specificity and sensitivity exist, opportunities such as multivariate analysis,
      development of multisite consortia for large-scale data collection, emergence of
      non-candidate gene (hypothesis-free) approach of neuroimaging genetics are likely
      to contribute to a rapid progress for gene discovery besides to gene validation
      studies that are related to SZ.

PMID- 29324667
TI  - Dietary Resveratrol Does Not Affect Life Span, Body Composition, Stress Response,
      and Longevity-Related Gene Expression in Drosophila melanogaster.
AB  - In this study, we tested the effect of the stilbene resveratrol on life span,
      body composition, locomotor activity, stress response, and the expression of
      genes encoding proteins centrally involved in ageing pathways in the model
      organism Drosophila melanogaster. Male and female w1118 D. melanogaster were fed
      diets based on sucrose, corn meal, and yeast. Flies either received a control
      diet or a diet supplemented with 500 umol/L resveratrol. Dietary resveratrol did
      not affect mean, median, and maximal life span of male and female flies.
      Furthermore, body composition remained largely unchanged following the
      resveratrol supplementation. Locomotor activity, as determined by the climbing
      index, was not significantly different between control and resveratrol
      supplemented flies. Resveratrol-fed flies did not exhibit an improved stress
      response towards hydrogen peroxide as compared to controls. Resveratrol did not
      change mRNA steady levels of antioxidant (catalase, glutathione-S-transferase,
      NADH dehydrogenase, glutathione peroxidase, superoxide dismutase 2) and longevity
      related genes, including sirtuin 2, spargel, and I'm Not Dead Yet. Collectively,
      present data suggest that resveratrol does not affect life span, body
      composition, locomotor activity, stress response, and longevity-associated gene
      expression in w1118 D. melanogaster.

PMID- 29324669
TI  - Nanoporous Polymers Based on Liquid Crystals.
AB  - In the present review, we discuss recent advances in the field of nanoporous
      networks based on polymerisable liquid crystals. The field has matured in the
      last decade, yielding polymers having 1D, 2D, and 3D channels with pore sizes on
      the nanometer scale. Next to the current progress, some of the future challenges
      are presented, with the integration of nanoporous membranes in functional devices
      considered as the biggest challenge.

PMID- 29324670
TI  - Dietary Carotenoid Intakes and Prostate Cancer Risk: A Case-Control Study from
      Vietnam.
AB  - The incidence of prostate cancer has increased in Vietnam, but there have been
      few studies of the risk factors associated with this change. This retrospective
      case-control study investigated the relation of the intake of carotenoids and
      their food sources to prostate cancer risk. A sample of 652 participants (244
      incident prostate cancer patients, aged 64-75 years, and 408 age frequency
      matched controls) were recruited in Ho Chi Minh City during 2013-2015. The
      habitual diet was ascertained with a validated food-frequency questionnaire, and
      other factors including demographic and lifestyle characteristics were assessed
      via face-to-face interviews by trained nurses. Multivariate-adjusted odds ratios
      (OR) and 95% confidence intervals (CI) were estimated using unconditional
      logistic regression models. The risk of prostate cancer decreased with increasing
      intakes of lycopene, tomatoes, and carrots; the respective ORs (95% CIs) were
      0.46 (0.27, 0.77), 0.39 (0.23, 0.66), and 0.35 (0.21, 0.58), when comparing the
      highest with the lowest tertile of intake (p for trend < 0.01). No statistically
      significant associations were found for the intake of alpha-carotene, beta
      carotene, beta-cryptoxanthin, lutein, zeaxanthin, and major food sources of
      carotenoids. In conclusion, Vietnamese men with a higher intake of lycopene,
      tomatoes, and carrots may have a lower risk of prostate cancer. However, large
      prospective studies are needed in this population to confirm this finding.

PMID- 29324671
TI  - Spatiotemporal Patterns of Ground Monitored PM2.5 Concentrations in China in
      Recent Years.
AB  - This paper firstly explores the space-time evolution of city-level PM 2.5
      concentrations showed a very significant seasonal cycle type fluctuation during
      the period between 13 May 2014 and 30 May 2017. The period from October to April
      following each year was a heavy pollution period, whereas the phase from April to
      October of the current year was part of a light pollution period. The average
      monthly PM 2.5 concentrations in mainland China based on ground monitoring,
      employing a descriptive statistics method and a Bayesian spatiotemporal hierarchy
      model. Daily and weekly average PM 2.5 concentrations in 338 cities in mainland
      China presented no significant spatial difference during the severe pollution
      period but a large spatial difference during light pollution periods. The severe
      PM 2.5 pollution areas were mainly distributed in the Beijing-Tianjin-Hebei urban
      agglomeration in the North China Plain during the beginning of each autumn-winter
      season (September), spreading to the Northeast Plains after October, then later
      continuing to spread to other cities in mainland China, eventually covering most
      cities. PM 2.5 pollution in China appeared to be a cyclic characteristic of first
      spreading and then centralizing in the space in two spring-summer seasons, and
      showed an obvious process of first diffusing then transferring to shrinkage
      alternation during the spring-summer season of 2015, but showed no obvious
      diffusion during the spring-summer season of 2016, maintaining a stable spatial
      structure after the shrinkage in June, as well as being more concentrated. The
      heavily polluted areas are continuously and steadily concentrated in East China,
      Central China and Xinjiang Province.

PMID- 29324672
TI  - Genome-Wide Identification, Expression, and Functional Analysis of the
      Alkaline/Neutral Invertase Gene Family in Pepper.
AB  - Alkaline/neutral invertase (NINV) proteins irreversibly cleave sucrose into
      fructose and glucose, and play important roles in carbohydrate metabolism and
      plant development. To investigate the role of NINVs in the development of pepper
      fruits, seven NINV genes (CaNINV1-7) were identified. Phylogenetic analysis
      revealed that the CaNINV family could be divided into alpha and beta groups.
      CaNINV1-6 had typical conserved regions and similar protein structures to the
      NINVs of other plants, while CaNINV7 lacked amino acid sequences at the C
      terminus and N-terminus ends. An expression analysis of the CaNINV genes in
      different tissues demonstrated that CaNINV5 is the dominant NINV in all the
      examined tissues (root, stem, leaf, bud, flower, and developmental pepper fruits
      stage). Notably, the expression of CaNINV5 was found to gradually increase at the
      pre-breaker stages, followed by a decrease at the breaker stages, while it
      maintained a low level at the post-breaker stages. Furthermore, the invertase
      activity of CaNINV5 was identified by functional complementation of the invertase
      deficient yeast strain SEY2102, and the optimum pH of CaNINV5 was found to be
      ~7.5. The gene expression and enzymatic activity of CaNINV5 suggest that it might
      be the main NINV enzyme for hydrolysis of sucrose during pepper fruit
      development.

PMID- 29324674
TI  - Calcitriol Supplementation Causes Decreases in Tumorigenic Proteins and Different
      Proteomic and Metabolomic Signatures in Right versus Left-Sided Colon Cancer.
AB  - Vitamin D deficiency is a common problem worldwide. In particular, it is an issue
      in the Northern Hemisphere where UVB radiation does not penetrate the atmosphere
      as readily. There is a correlation between vitamin D deficiency and colorectal
      cancer incidence and mortality. Furthermore, there is strong evidence that cancer
      of the ascending (right side) colon is different from cancer of the descending
      (left side) colon in terms of prognosis, tumor differentiation, and polyp type,
      as well as at the molecular level. Right-side tumors have elevated Wnt signaling
      and are more likely to relapse, whereas left-side tumors have reduced expression
      of tumor suppressor genes. This study seeks to understand both the proteomic and
      metabolomic changes resulting from treatment of the active metabolite of vitamin
      D, calcitriol, in right-sided and left-sided colon cancer. Our results show that
      left-sided colon cancer treated with calcitriol has a substantially greater
      number of changes in both the proteome and the metabolome than right-sided colon
      cancer. We found that calcitriol treatment in both right-sided and left-sided
      colon cancer causes a downregulation of ribosomal protein L37 and protein
      S100A10. Both of these proteins are heavily involved in tumorigenesis, suggesting
      a possible mechanism for the correlation between low vitamin D levels and colon
      cancer.

PMID- 29324675
TI  - A Time-Domain Analog Spatial Compressed Sensing Encoder for Multi-Channel Neural
      Recording.
AB  - A time-domain analog spatial compressed sensing encoder for neural recording
      applications is proposed. Owing to the advantage of MEMS technologies, the number
      of channels on a silicon neural probe array has doubled in 7.4 years, and
      therefore, a greater number of recording channels and higher density of front-end
      circuitry is required. Since neural signals such as action potential (AP) have
      wider signal bandwidth than that of an image sensor, a data compression technique
      is essentially required for arrayed neural recording systems. In this paper,
      compressed sensing (CS) is employed for data reduction, and a novel time-domain
      analog CS encoder is proposed. A simpler and lower power circuit than
      conventional analog or digital CS encoders can be realized by using the proposed
      CS encoder. A prototype of the proposed encoder was fabricated in a 180 nm 1P6M
      CMOS process, and it achieved an active area of 0.0342 mm 2 / ch . and an energy
      efficiency of 25.0 pJ / ch . . conv .

PMID- 29324676
TI  - Enantiomeric Resolution and Docking Studies of Chiral Xanthonic Derivatives on
      Chirobiotic Columns.
AB  - A systematic study of enantioresolution of a library of xanthonic derivatives,
      prepared "in-house", was successfully carried out with four commercially
      available macrocyclic glycopeptide-based columns, namely ChirobioticTM T,
      ChirobioticTM R, ChirobioticTM V and ChirobioticTM TAG. Evaluation was conducted
      in multimodal elution conditions: normal-phase, polar organic, polar ionic and
      reversed-phase. The effects of the mobile phase composition, the percentage of
      organic modifier, the pH of the mobile phase, the nature and concentration of
      different mobile phase additives on the chromatographic parameters are discussed.
      ChirobioticTM T and ChirobioticTM V, under normal-phase and reversed-phase modes,
      respectively, presented the best chromatographic parameters. Considering the
      importance of understanding the chiral recognition mechanisms associated with the
      chromatographic enantioresolution, and the scarce data available for macrocyclic
      glycopeptide-based columns, computational studies by molecular docking were also
      carried out.

PMID- 29324677
TI  - Dinuclear Nickel(I) and Palladium(I) Complexes for Highly Active Transformations
      of Organic Compounds.
AB  - In typical catalytic organic transformations, transition metals in catalytically
      active complexes are present in their most stable valence states, such as
      palladium(0) and (II). However, some dimeric monovalent metal complexes can be
      stabilized by auxiliary ligands to form diamagnetic compounds with metal-metal
      bonding interactions. These diamagnetic compounds can act as catalysts while
      retaining their dimeric forms, split homolytically or heterolytically into
      monomeric forms, which usually have high activity, or in contrast, become
      completely deactivated as catalysts. Recently, many studies using group 10 metal
      complexes containing nickel and palladium have demonstrated that under specific
      conditions, the active forms of these catalyst precursors are not mononuclear
      zerovalent complexes, but instead dinuclear monovalent metal complexes. In this
      mini-review, we have surveyed the preparation, reactivity, and the catalytic
      processes of dinuclear nickel(I) and palladium(I) complexes, focusing on
      mechanistic insights into the precatalyst activation systems and the structure
      and behavior of nickel and palladium intermediates.

PMID- 29324678
TI  - Immobilization of Enzymes on a Phospholipid Bionically Modified Polysulfone
      Gradient-Pore Membrane for the Enhanced Performance of Enzymatic Membrane
      Bioreactors.
AB  - Enzymatic membrane bioreactors (EMBRs), with synergistic catalysis-separation
      performance, have increasingly been used for practical applications. Generally,
      the membrane properties, particularly the pore structures and interface
      interactions, have a significant impact on the catalytic efficiency of the EMBR.
      Therefore, a biomimetic interface based on a phospholipid assembled onto a
      polysulfone hollow-fiber membrane with perfect radial gradient pores (RGM-PSF)
      has been prepared in this work to construct a highly efficient and stable EMBR.
      On account of the special pore structure of the RGM-PSF with the apertures
      decreasing gradually from the inner side to the outer side, the enzyme molecules
      could be evenly distributed on the three-dimensional skeleton of the membrane. In
      addition, the supported phospholipid layer in the membrane, prepared by physical
      adsorption, was used for the immobilization of the enzymes, which provides
      sufficient linkage to prevent the enzymes from leaching but also accommodates as
      many enzyme molecules as possible to retain high bioactivity. The properties of
      the EMBR were studied by using lipase from Candida rugosa for the hydrolysis of
      glycerol triacetate as a model. Energy-dispersive X-ray and circular dichroism
      spectroscopy were employed to observe the effect of lecithin on the membrane and
      structure changes in the enzyme, respectively. The operational conditions were
      investigated to optimize the performance of the EMBR by testing substrate
      concentrations from 0.05 to 0.25 M, membrane fluxes from 25.5 to 350.0 L.m-2.h-1,
      and temperatures from 15 to 55  degrees C. As a result, the obtained EMBR showed
      a desirable performance with 42% improved enzymatic activity and 78% improved
      catalytic efficiency relative to the unmodified membrane.

PMID- 29324679
TI  - Antibacterial Evaluation and Virtual Screening of New Thiazolyl-Triazole Schiff
      Bases as Potential DNA-Gyrase Inhibitors.
AB  - The global spread of bacterial resistance to drugs used in therapy requires new
      potent and safe antimicrobial agents. DNA gyrases represent important targets in
      drug discovery. Schiff bases, thiazole, and triazole derivatives are considered
      key scaffolds in medicinal chemistry. Fifteen thiazolyl-triazole Schiff bases
      were evaluated for their antibacterial activity, measuring the growth inhibition
      zone diameter, the minimum inhibitory concentration (MIC), and the minimum
      bactericidal concentration (MBC), against Gram-positive (Staphylococcus aureus,
      Listeria monocytogenes) and Gram-negative (Escherichia coli, Salmonella
      typhimurium, Pseudomonas aeruginosa) bacteria. The inhibition of S. aureus and S.
      typhimurium was modest. Compounds B1, B2, and B9 showed a similar effect as
      ciprofloxacin, the antimicrobial reference, against L. monocytogenes. B10
      displayed a better effect. Derivatives B1, B5-7, B9, and B11-15 expressed MIC
      values lower than the reference, against L. monocytogenes. B5, B6, and B11-15
      strongly inhibited the growth of P. aeruginosa. All compounds were subjected to
      an in silico screening of the ADMET (absorption, distribution, metabolism,
      elimination, toxicity) properties. Molecular docking was performed on the gyrA
      and gyrB from L. monocytogenes. The virtual screening concluded that thiazolyl
      triazole Schiff base B8 is the best drug-like candidate, satisfying requirements
      for both safety and efficacy, being more potent against the bacterial gyrA than
      ciprofloxacin.

PMID- 29324680
TI  - Phylogenetic Analysis and Characterization of a Sporadic Isolate of Equine
      Influenza A H3N8 from an Unvaccinated Horse in 2015.
AB  - Equine influenza, caused by the H3N8 subtype, is a highly contagious respiratory
      disease affecting equid populations worldwide and has led to serious epidemics
      and transboundary pandemics. This study describes the phylogenetic
      characterization and replication kinetics of recently-isolated H3N8 virus from a
      nasal swab obtained from a sporadic case of natural infection in an unvaccinated
      horse from Montana, USA. The nasal swab tested positive for equine influenza by
      Real-Time Quantitative Reverse Transcription Polymerase Chain Reaction (RT-PCR).
      Further, the whole genome sequencing of the virus confirmed that it was the H3N8
      subtype and was designated as A/equine/Montana/9564-1/2015 (H3N8). A BLASTn
      search revealed that the polymerase basic protein 1 (PB1), polymerase acidic
      (PA), hemagglutinin (HA), nucleoprotein (NP), and matrix (M) segments of this
      H3N8 isolate shared the highest percentage identity to
      A/equine/Tennessee/29A/2014 (H3N8) and the polymerase basic protein 2 (PB2),
      neuraminidase (NA), and non-structural protein (NS) segments to
      A/equine/Malaysia/M201/2015 (H3N8). Phylogenetic characterization of individual
      gene segments, using currently available H3N8 viral genomes, of both equine and
      canine origin, further established that A/equine/Montana/9564-1/2015 belonged to
      the Florida Clade 1 viruses. Interestingly, replication kinetics of this H3N8
      virus, using airway derived primary cells from multiple species, such as equine,
      swine, bovine, and human lung epithelial cells, demonstrated appreciable titers,
      when compared to Madin-Darby canine kidney epithelial cells. These findings
      indicate the broad host spectrum of this virus isolate and suggest the potential
      for cross-species transmissibility.

PMID- 29324681
TI  - PPoma Review: Epidemiology, Aetiopathogenesis, Prognosis and Treatment.
AB  - Generally, pancreatic polypeptide-secreting tumor of the distal pancreas (PPoma)
      is classified as a rare tumor, and may occur sporadically or be associated in
      families or with multiple endocrine neoplasia type 1 (NEM 1). It grows slowly,
      reaching large dimensions at the time of diagnosis and the symptomatology is
      fundamentally due to the mass effect, causing either non-specific abdominal pain
      or symptoms suggestive of obstruction of the pancreatic or biliary duct.
      Therefore, when detected, they are usually malignant, with metastases mainly in
      the liver. The combination of serum analysis of increased levels of chromogranin
      A and pancreatic polypeptide and pancreastatin is very useful with a sensitivity
      of up to 95%. However, in addition, scintigraphicexams with somatostatin
      analogues should be performed to better clarify the diagnosis. Surgical resection
      is the treatment of choice, despite surgical difficulty and because they are
      generally palliative due to the metastases. Surgeries for tumor volume reduction
      are also performed to relieve symptoms. Chemotherapy commonly uses streptozotocin
      and somatostatin analogues to treat residual disease. Unfortunately, the survival
      rates are still very low, less than 10%, and if metastases already exist, this
      percentage drops to 3%.

PMID- 29324682
TI  - Malnutrition, Inflammation, Atherosclerosis Syndrome (MIA) and Diet
      Recommendations among End-Stage Renal Disease Patients Treated with Maintenance
      Hemodialysis.
AB  - Malnutrition-inflammation-atherosclerosis syndrome is one of the causes of
      increased mortality in chronic kidney disease (CKD). The aim of the study was to
      assess the inflammation and nutritional status of patients in end-stage kidney
      disease treated with maintenance hemodialysis. The study included a group of 98
      hemodialyzed patients with stage 5 CKD (38 women and 60 men). Albumin, prealbumin
      (PRE), and C-reactive protein (CRP) were measured in serum samples collected
      before mid-week dialysis. Fruit and vegetables frequency intakes were assessed
      with a questionnaire. CRP was above the reference limit of 5 mg/L in 53% of
      patients. Moreover, the Glasgow Prognostic Score (GPS) indicated the co
      occurrence of inflammation and protein calorie malnutrition in 11% of patients,
      and the presence of either inflammation or malnutrition in 25%. The questionnaire
      revealed that hemodialyzed patients frequently exclude fruit and vegetables from
      their diets. Nearly 43% of the interviewed patients declared frequently eating
      vegetables, and 35% declared frequently eating fruit, a few times per week or
      less. The most frequently selected fruit and vegetables had a low antioxidant
      capacity. The strict dietary restrictions in CKD are difficult to fulfill, and if
      strictly followed, may lead to protein-calorie malnutrition.

PMID- 29324684
TI  - Comparative Effect of Self- or Dual-Curing on Polymerization Kinetics and
      Mechanical Properties in a Novel, Dental-Resin-Based Composite with Alkaline
      Filler. Running Title: Resin-Composites with Alkaline Fillers.
AB  - Dental bulk-fill restorations with resin-composites (RBC) are increasing in
      popularity, but doubts concerning insufficient curing in depth still disconcert
      clinicians. An alternative might be offered by modern dual-cured RBCs, which
      additionally provide bioactive properties. This study assessed the impact of
      additional light-curing on polymerization kinetics, the degree of conversion (DC)
      and mechanical properties of a novel, dual-cured RBC with alkaline fillers. Since
      the bioactivity of a material often implies a release of compounds, the
      mechanical stability in simulated clinical environments was also evaluated.
      Polymerization kinetics and DC were assessed at 2- and 4-mm specimen depths in
      real-time up to one hour (n = 6). Incident and transmitted irradiance and radiant
      exposure were recorded at 2- and 4-mm depths. Micro-mechanical profiles (n = 6)
      were assessed in 100-um steps along 6-mm deep specimens at 24 h post
      polymerization. Flexural strength and modulus (n = 10) were determined up to
      three months of immersion in neutral (6.8) and acidic (4) pH conditions. DC
      variation in time was best described by a sigmoidal function (R2 > 0.98),
      revealing a retarded (3.4 +/- 0.4 min) initiation in C=C double bond conversion
      in self-cured versus dual-cured specimens. The setting reaction kinetic was
      identical at 2- and 4-mm depths for the self-cure mode. For the dual-cure mode,
      polymerization initiated at 2-mm depth instantly with light-irradiation, while
      being retarded (0.8 min) at 4-mm depth. The material behaves similarly,
      irrespective of curing mode or depth, later than 11 min after mixing. Flexural
      strength and modulus was comparable to regular RBCs and maintained up to three
      months in both neutral and acidic conditions. Additional light-curing initially
      accelerates the polymerization kinetic and might help shorten the restauration
      procedure by hardening the material on demand, however with no effect on the
      final properties.

PMID- 29324683
TI  - Pentoxifylline and Methylprednisolone Additively Alleviate Kidney Failure and
      Prolong Survival of Rats after Renal Warm Ischemia-Reperfusion.
AB  - Renal ischemia-reperfusion injury (IRI) induces local inflammation leading to
      kidney damage. Since pentoxifylline (PTX) and steroids have distinct
      immunomodulatory properties, we aimed to evaluate for the first time their
      combined use in IRI-induced acute kidney injury (AKI) and chronic kidney disease
      (CKD) in rats. In two experiments, PTX (100 mg/kg body weight subcutaneously) was
      administered 90 min prior to renal IRI or/and methylprednisolone (MP; 100 mg/kg
      body weight intramuscularly) was infused 60 min after reperfusion of a solitary
      kidney (AKI model: 45 min ischemia, 48 male Sprague-Dawley rats) or one kidney
      with excision of contralateral kidney 2 weeks later (CKD model: 90 min ischemia,
      38 rats). Saline was infused in place of PTX or/and MP depending on the group.
      Renal function (diuresis, serum creatinine, creatinine clearance, sodium and
      potassium excretion, and urine protein/creatinine) was assessed at 48 h and 120 h
      post-IRI (AKI model) or 4, 16 and 24 weeks after IRI, along with survival
      analysis (CKD model). More evidently at early stages of AKI or CKD, treated
      animals showed higher glomerular filtration and diminished tubular loss of
      electrolytes, more so with PTX + MP than PTX or MP (serum creatinine (MUmol/L) at
      48 h of AKI: 60.9 +/- 19.1 vs. 131.1 +/- 94.4 vs. 233.4 +/- 137.0, respectively,
      vs. 451.5 +/- 114.4 in controls, all p < 0.05; and at 4 weeks of CKD: 89.0 +/-
      31.9 vs. 118.1 +/- 64.5 vs. 156.9 +/- 72.6, respectively, vs. 222.9 +/- 91.4 in
      controls, p < 0.05 for PTX or PTX + MP vs. controls and PTX + MP vs. MP).
      Survival was better by >2-fold with PTX + MP (89%) vs. controls (40%; p < 0.05).
      PTX + MP largely protect from IRI-induced AKI and CKD and subsequent mortality in
      rats. This calls for clinical investigations, especially in kidney
      transplantation.

PMID- 29324686
TI  - Theoretical Analysis and Design of Ultrathin Broadband Optically Transparent
      Microwave Metamaterial Absorbers.
AB  - Optically Transparent Microwave Metamaterial Absorber (OTMMA) is of significant
      use in both civil and military field. In this paper, equivalent circuit model is
      adopted as springboard to navigate the design of OTMMA. The physical model and
      absorption mechanisms of ideal lightweight ultrathin OTMMA are comprehensively
      researched. Both the theoretical value of equivalent resistance and the
      quantitative relation between the equivalent inductance and equivalent
      capacitance are derived for design. Frequency-dependent characteristics of
      theoretical equivalent resistance are also investigated. Based on these
      theoretical works, an effective and controllable design approach is proposed. To
      validate the approach, a wideband OTMMA is designed, fabricated, analyzed and
      tested. The results reveal that high absorption more than 90% can be achieved in
      the whole 6~18 GHz band. The fabricated OTMMA also has an optical transparency up
      to 78% at 600 nm and is much thinner and lighter than its counterparts.

PMID- 29324685
TI  - Novel Spectroscopic and Electrochemical Sensors and Nanoprobes for the
      Characterization of Food and Biological Antioxidants.
AB  - Since an unbalanced excess of reactive oxygen/nitrogen species (ROS/RNS) causes
      various diseases, determination of antioxidants that can counter oxidative stress
      is important in food and biological analyses. Optical/electrochemical nanosensors
      have attracted attention in antioxidant activity (AOA) assessment because of
      their increased sensitivity and selectivity. Optical sensors offer advantages
      such as low cost, flexibility, remote control, speed, miniaturization and on
      site/in situ analysis. Electrochemical sensors using noble metal nanoparticles on
      modified electrodes better catalyze bioelectrochemical reactions. We summarize
      the design principles of colorimetric sensors and nanoprobes for food
      antioxidants (including electron-transfer based and ROS/RNS scavenging assays)
      and important milestones contributed by our laboratory. We present novel sensors
      and nanoprobes together with their mechanisms and analytical performances. Our
      colorimetric sensors for AOA measurement made use of cupric-neocuproine and
      ferric-phenanthroline complexes immobilized on a Nafion membrane. We recently
      designed an optical oxidant/antioxidant sensor using N,N-dimethyl-p-phenylene
      diamine (DMPD) as probe, from which ROS produced colored DMPD-quinone cationic
      radicals electrostatically retained on a Nafion membrane. The attenuation of
      initial color by antioxidants enabled indirect AOA estimation. The surface
      plasmon resonance absorption of silver nanoparticles as a result of enlargement
      of citrate-reduced seed particles by antioxidant addition enabled a linear
      response of AOA. We determined biothiols with Ellman reagent-derivatized gold
      nanoparticles.

PMID- 29324687
TI  - Intraperitoneal Administration of Oxygen/Ozone to Rats Reduces the Pancreatic
      Damage Induced by Streptozotocin.
AB  - Background: The rat model of streptozotocin (STZ)-induced pancreatic damage was
      used to examine whether a systemic oxygen/ozone mixture could be beneficial for
      the pancreas by reducing the machinery of the local detrimental mediators
      released by STZ. Results: The results showed that oxygen/ozone administration
      (150 ug/Kg i.p.) for ten days in STZ rats increased the endogenous glutathione-s
      transferase (GST) enzyme and nuclear factor-erythroid 2-related factor 2 (Nrf2)
      into the pancreatic tissue, together with reduction of 4-hydroxynonenal (4-HNE)
      and PARP-1 compared to STZ rats receiving O2 only. Interestingly, these changes
      resulted in higher levels of serum insulin and leptin, and pancreatic glucagon
      immunostaining. Consequently, glucose metabolism improved as evidenced by the
      monitoring of glycemia throughout. Conclusions: This study provides evidence that
      systemic administration of oxygen/ozone reduces the machinery of detrimental
      mediators released by STZ into the pancreas with less local damage and better
      functionality.

PMID- 29324688
TI  - On Multi-Objective Based Constitutive Modelling Methodology and Numerical
      Validation in Small-Hole Drilling of Al6063/SiCp Composites.
AB  - Discrepancies in capturing material behavior of some materials, such as
      Particulate Reinforced Metal Matrix Composites, by using conventional ad hoc
      strategy make the applicability of Johnson-Cook constitutive model challenged.
      Despites applicable efforts, its extended formalism with more fitting parameters
      would increase the difficulty in identifying constitutive parameters. A weighted
      multi-objective strategy for identifying any constitutive formalism is developed
      to predict mechanical behavior in static and dynamic loading conditions equally
      well. These varying weighting is based on the Gaussian-distributed noise
      evaluation of experimentally obtained stress-strain data in quasi-static or
      dynamic mode. This universal method can be used to determine fast and directly
      whether the constitutive formalism is suitable to describe the material
      constitutive behavior by measuring goodness-of-fit. A quantitative comparison of
      different fitting strategies on identifying Al6063/SiCp's material parameters is
      made in terms of performance evaluation including noise elimination, correlation,
      and reliability. Eventually, a three-dimensional (3D) FE model in small-hole
      drilling of Al6063/SiCp composites, using multi-objective identified constitutive
      formalism, is developed. Comparison with the experimental observations in thrust
      force, torque, and chip morphology provides valid evidence on the applicability
      of the developed multi-objective identification strategy in identifying
      constitutive parameters.

PMID- 29324689
TI  - Characterization of Translationally Controlled Tumour Protein from the Sea
      Anemone Anemonia viridis and Transcriptome Wide Identification of Cnidarian
      Homologues.
AB  - Gene family encoding translationally controlled tumour protein (TCTP) is defined
      as highly conserved among organisms; however, there is limited knowledge of non
      bilateria. In this study, the first TCTP homologue from anthozoan was
      characterised in the Mediterranean Sea anemone, Anemonia viridis. The release of
      the genome sequence of Acropora digitifera, Exaiptasia pallida, Nematostella
      vectensis and Hydra vulgaris enabled a comprehensive study of the molecular
      evolution of TCTP family among cnidarians. A comparison among TCTP members from
      Cnidaria and Bilateria showed conserved intron exon organization, evolutionary
      conserved TCTP signatures and 3D protein structure. The pattern of mRNA
      expression profile was also defined in A. viridis. These analyses revealed a
      constitutive mRNA expression especially in tissues with active proliferation.
      Additionally, the transcriptional profile of A. viridis TCTP (AvTCTP) after
      challenges with different abiotic/biotic stresses showed induction by extreme
      temperatures, heavy metals exposure and immune stimulation. These results suggest
      the involvement of AvTCTP in the sea anemone defensome taking part in
      environmental stress and immune responses.

PMID- 29324690
TI  - Effects of Agitation, Aeration and Temperature on Production of a Novel
      Glycoprotein GP-1 by Streptomyces kanasenisi ZX01 and Scale-Up Based on
      Volumetric Oxygen Transfer Coefficient.
AB  - The effects of temperature, agitation and aeration on glycoprotein GP-1
      production by Streptomyces kanasenisi ZX01 in bench-scale fermentors were
      systematically investigated. The maximum final GP-1 production was achieved at an
      agitation speed of 200 rpm, aeration rate of 2.0 vvm and temperature of 30 
      degrees C. By using a dynamic gassing out method, the effects of agitation and
      aeration on volumetric oxygen transfer coefficient (kLa) were also studied. The
      values of volumetric oxygen transfer coefficient in the logarithmic phase
      increased with increase of agitation speed (from 14.53 to 32.82 h-1) and aeration
      rate (from 13.21 to 22.43 h-1). In addition, a successful scale-up from bench
      scale to pilot-scale was performed based on volumetric oxygen transfer
      coefficient, resulting in final GP-1 production of 3.92, 4.03, 3.82 and 4.20 mg/L
      in 5 L, 15 L, 70 L and 500 L fermentors, respectively. These results indicated
      that constant volumetric oxygen transfer coefficient was appropriate for the
      scale-up of batch fermentation of glycoprotein GP-1 by Streptomyces kanasenisi
      ZX01, and this scale-up strategy successfully achieved 100-fold scale-up from
      bench-scale to pilot-scale fermentor.

PMID- 29324691
TI  - Physiological and Comparative Genomic Analysis of Arthrobacter sp. SRS-W-1-2016
      Provides Insights on Niche Adaptation for Survival in Uraniferous Soils.
AB  - Arthrobacter sp. strain SRS-W-1-2016 was isolated on high concentrations of
      uranium (U) from the Savannah River Site (SRS) that remains co-contaminated by
      radionuclides, heavy metals, and organics. SRS is located on the northeast bank
      of the Savannah River (South Carolina, USA), which is a U.S. Department of Energy
      (DOE) managed ecosystem left historically contaminated from decades of nuclear
      weapons production activities. Predominant contaminants within the impacted SRS
      environment include U and Nickel (Ni), both of which can be transformed
      microbially into less toxic forms via metal complexation mechanisms. Strain SRS-W
      1-2016 was isolated from the uraniferous SRS soils on high concentrations of U
      (4200 MUM) and Ni (8500 MUM), but rapid growth was observed at much lower
      concentrations of 500 MUM U and 1000 MUM Ni, respectively. Microcosm studies
      established with strain SRS-W-1-2016 revealed a rapid decline in the
      concentration of spiked U such that it was almost undetectable in the supernatant
      by 72 h of incubation. Conversely, Ni concentrations remained unchanged,
      suggesting that the strain removed U but not Ni under the tested conditions. To
      obtain a deeper understanding of the metabolic potential, a draft genome sequence
      of strain SRS-W-1-2016 was obtained at a coverage of 90*, assembling into 93
      contigs with an N50 contig length of 92,788 bases. The genomic size of strain SRS
      W-1-2016 was found to be 4,564,701 bases with a total number of 4327 putative
      genes. An in-depth, genome-wide comparison between strain SRS-W-1-2016 and its
      four closest taxonomic relatives revealed 1159 distinct genes, representing 26.7%
      of its total genome; many associating with metal resistance proteins (e.g., for
      cadmium, cobalt, and zinc), transporter proteins, stress proteins, cytochromes,
      and drug resistance functions. Additionally, several gene homologues coding for
      resistance to metals were identified in the strain, such as outer membrane efflux
      pump proteins, peptide/nickel transport substrate and ATP-binding proteins, a
      high-affinity nickel-transport protein, and the spoT gene, which was recently
      implicated in bacterial resistance towards U. Detailed genome mining analysis of
      strain SRS-W-1-2016 also revealed the presence of a plethora of secondary
      metabolite biosynthetic gene clusters likely facilitating resistance to
      antibiotics, biocides, and metals. Additionally, several gene homologous for the
      well-known oxygenase enzyme system were also identified, potentially functioning
      to generate energy via the breakdown of organic compounds and thus enabling the
      successful colonization and natural attenuation of contaminants by Arthrobacter
      sp. SRS-W-1-2016 at the SRS site.

PMID- 29324692
TI  - A Portable Dynamic Laser Speckle System for Sensing Long-Term Changes Caused by
      Treatments in Painting Conservation.
AB  - Dynamic laser speckle (DLS) is used as a reliable sensor of activity for all
      types of materials. Traditional applications are based on high-rate captures
      (usually greater than 10 frames-per-second, fps). Even for drying processes in
      conservation treatments, where there is a high level of activity in the first
      moments after the application and slower activity after some minutes or hours,
      the process is based on the acquisition of images at a time rate that is the same
      in moments of high and low activity. In this work, we present an alternative
      approach to track the drying process of protective layers and other painting
      conservation processes that take a long time to reduce their levels of activity.
      We illuminate, using three different wavelength lasers, a temporary protector
      (cyclododecane) and a varnish, and monitor them using a low fps rate during long
      term drying. The results are compared to the traditional method. This work also
      presents a monitoring method that uses portable equipment. The results present
      the feasibility of using the portable device and show the improved sensitivity of
      the dynamic laser speckle when sensing the long-term process for drying
      cyclododecane and varnish in conservation.

PMID- 29324694
TI  - Influence of Nb on the Microstructure and Fracture Toughness of (Zr0.76Fe0.24)100
      xNbx Nano-Eutectic Composites.
AB  - The present study demonstrates the evolution of eutectic microstructure in arc
      melted (Zr0.76Fe0.24)100-xNbx (0 <= x <= 10 atom %) composites containing alpha
      Zr//FeZr2 nano-lamellae phases along with pro-eutectic Zr-rich intermetallic
      phase. The effects of Nb addition on the microstructural evolution and mechanical
      properties under compression, bulk hardness, elastic modulus, and indentation
      fracture toughness (IFT) were investigated. The Zr-Fe-(Nb) eutectic composites
      (ECs) exhibited excellent fracture strength up to ~1800 MPa. Microstructural
      characterization revealed that the addition of Nb promotes the formation of
      intermetallic Zr54Fe37Nb9. The IFT (KIC) increases from 3.0 +/- 0.5 MPa?m (x = 0)
      to 4.7 +/- 1.0 MPa?m (x = 2) at 49 N, which even further increases from 5.1 +/-
      0.5 MPa?m (x = 0) and up to 5.9 +/- 1.0 MPa?m (x = 2) at higher loads. The
      results suggest that mutual interaction between nano-lamellar alpha-Zr//FeZr2
      phases is responsible for enhanced fracture resistance and high fracture
      strength.

PMID- 29324693
TI  - Inhibiting the Physiological Stress Effects of a Sustained Attention Task on
      Shoulder Muscle Activity.
AB  - OBJECTIVE: The objective of this study was to investigate if a breathing
      technique could counteract the effects of hyperventilation due to a sustained
      attention task on shoulder muscle activity. BACKGROUND: The trend towards higher
      levels of automation in industry is increasing. Consequently, manufacturing
      operators often monitor automated process for long periods of their work shift.
      Prolonged monitoring work requires sustained attention, which is a cognitive
      process that humans are typically poor at and find stressful. As sustained
      attention becomes an increasing requirement of manufacturing operators' job
      content, the resulting stress experienced could contribute to the onset of many
      health problems, including work related musculoskeletal disorders (WRMSDs).
      METHODS: The SART attention test was completed by a group of participants before
      and after a breathing intervention exercise. The effects of the abdominal
      breathing intervention on breathing rate, upper trapezius muscle activity and end
      tidal CO2 were evaluated. RESULTS: The breathing intervention reduced the
      moderation effect of end-tidal CO2 on upper trapezius muscle activity.
      CONCLUSIONS: Abdominal breathing could be a useful technique in reducing the
      effects of sustained attention work on muscular activity. APPLICATION: This
      research can be applied to highly-automated manufacturing industries, where
      prolonged monitoring of work is widespread and could, in its role as a stressor,
      be a potential contributor to WRMSDs.

PMID- 29324696
TI  - Quantitative Assessment of Antimicrobial Activity of PLGA Films Loaded with 4
      Hexylresorcinol.
AB  - Profound screening and evaluation methods for biocide-releasing polymer films are
      crucial for predicting applicability and therapeutic outcome of these drug
      delivery systems. For this purpose, we developed an agar overlay assay embedding
      biopolymer composite films in a seeded microbial lawn. By combining this approach
      with model-dependent analysis for agar diffusion, antimicrobial potency of the
      entrapped drug can be calculated in terms of minimum inhibitory concentrations
      (MICs). Thus, the topical antiseptic 4-hexylresorcinol (4-HR) was incorporated
      into poly(lactic-co-glycolic acid) (PLGA) films at different loadings up to 3.7
      mg/cm2 surface area through a solvent casting technique. The antimicrobial
      activity of 4-HR released from these composite films was assessed against a panel
      of Gram-negative and Gram-positive bacteria, yeasts and filamentous fungi by the
      proposed assay. All the microbial strains tested were susceptible to PLGA-4-HR
      films with MIC values down to 0.4% (w/w). The presented approach serves as a
      reliable method in screening and quantifying the antimicrobial activity of
      polymer composite films. Moreover, 4-HR-loaded PLGA films are a promising
      biomaterial that may find future application in the biomedical and packaging
      sector.

PMID- 29324695
TI  - Investigation into Improving the Aqueous Solubility of the Thieno[2,3-b]pyridine
      Anti-Proliferative Agents.
AB  - It is now established that the thieno[2,3-b]pyridines are a potent class of
      antiproliferatives. One of the main issues encountered for their clinical
      application is their low water solubility. In order to improve this, two
      strategies were pursued. First, a morpholine moiety was tethered to the molecular
      scaffold by substituting the sulphur atom with nitrogen, resulting in a 1H
      pyrrolo[2,3-b]pyridine core structure. The water solubility was increased by
      three orders of magnitude, from 1.2 ug/mL (1-thieno[2,3-b]pyridine) to 1.3 mg/mL
      (3-pyrrolo[2,3-b]pyridine), however, it was only marginally active against cancer
      cells. The second strategy involved loading a very potent thieno[2,3-b]pyridine
      derivative (2) into a cholesteryl-poly(allylamine) polymer matrix for water
      solubilisation. Suppression of human pancreatic adenocarcinoma (BxPC-3) viability
      was observed to an IC50 value of 0.5 MUg/mL (1.30 MUM) in conjunction with the
      polymer, which is a five-fold (*5) increase in potency as compared to the free
      drug alone, demonstrating the utility of this formulation approach.

PMID- 29324698
TI  - An Improved Coarse Alignment Algorithm for Odometer-Aided SINS Based on the
      Optimization Design Method.
AB  - An improved coarse alignment (ICA) algorithm is proposed in this paper with a
      focus on improving alignment accuracy of odometer-aided strapdown inertial
      navigation system (SINS) under variable velocity and variable acceleration
      condition. In the proposed algorithm, the outputs of inertial sensors and
      odometer in a sampling interval are linearized rather than assumed to be a
      constant, which improves the accuracy of the vector observations and the
      precision of coarse alignment. Simulation and field test results illustrate that,
      under variable velocity and variable acceleration condition, the proposed
      algorithm can obtain a better alignment performance than conventional coarse
      alignment method.

PMID- 29324697
TI  - Association between Fetal Adipokines and Child Behavioral Problems at Preschool
      Age: The Hokkaido Study on Environment and Children's Health.
AB  - Studies have suggested associations between maternal obesity and mental health
      problems of their children. However, the underlying mechanism is largely unknown.
      A possible mechanism can be via inflammatory states and the other possible
      mechanism is metabolic hormone-induced programming. Cross-talk between
      adipokines, including inflammatory cytokines and metabolic hormones secreted from
      adipose tissue and the central nervous system needs to be further investigated to
      elucidate the mechanism. Thus, the aim of this study was to investigate the
      association between fetal adipokine levels and child behavioral problems at
      preschool age. Cord blood adiponectin, leptin, tumor necrosis factor-alpha (TNF
      alpha) and interleukin 6 (IL-6) levels were measured and child behavioral
      problems were assessed using the Strengths and Difficulties Questionnaire at
      preschool age. Logistic regression models adjusted by related maternal factors
      were performed to examine the association between cord blood adipokines and child
      behavioral problems. Three hundred and sixty-one children were included in the
      final analysis. A significant association between decreased
      hyperactivity/inattention and increased leptin was found (OR = 0.22, 95% CI: 0.06
      0.89). Cord blood adiponectin, TNF-alpha and IL-6 levels were not associated with
      child behavioral problems. Our findings suggested that cord blood adipokines,
      particularly, leptin level, may be a predictor of hyperactivity/inattention
      problems at preschool age.

PMID- 29324699
TI  - LED-CT Scan for pH Distribution on a Cross-Section of Cell Culture Medium.
AB  - In cell culture, the pH of the culture medium is one of the most important
      conditions. However, the culture medium may have non-uniform pH distribution due
      to activities of cells and changes in the environment. Although it is possible to
      measure the pH distribution with an existing pH meter using distributed
      electrodes, the method involves direct contact with the medium and would greatly
      increase the risk of contamination. Here in this paper, we propose a computed
      tomography (CT) scan for measuring pH distribution using the color change of
      phenol red with a light-emitting diode (LED) light source. Using the principle of
      CT scan, we can measure pH distribution without contacting culture medium, and
      thus, decrease the risk of contamination. We have developed the device with a
      LED, an array of photo receivers and a rotation mechanism. The system is firstly
      calibrated with different shapes of wooden objects that do not pass light, we
      succeeded in obtaining their 3D topographies. The system was also used for
      measuring a culture medium with two different pH values, it was possible to
      obtain a pH distribution that clearly shows the boundary.

PMID- 29324700
TI  - Predicting Lameness in Sheep Activity Using Tri-Axial Acceleration Signals.
AB  - Lameness is a clinical symptom associated with a number of sheep diseases around
      the world, having adverse effects on weight gain, fertility, and lamb birth
      weight, and increasing the risk of secondary diseases. Current methods to
      identify lame animals rely on labour intensive visual inspection. The aim of this
      current study was to determine the ability of a collar, leg, and ear attached tri
      axial accelerometer to discriminate between sound and lame gait movement in
      sheep. Data were separated into 10 s mutually exclusive behaviour epochs and
      subjected to Quadratic Discriminant Analysis (QDA). Initial analysis showed the
      high misclassification of lame grazing events with sound grazing and standing
      from all deployment modes. The final classification model, which included lame
      walking and all sound activity classes, yielded a prediction accuracy for lame
      locomotion of 82%, 35%, and 87% for the ear, collar, and leg deployments,
      respectively. Misclassification of sound walking with lame walking within the leg
      accelerometer dataset highlights the superiority of an ear mode of attachment for
      the classification of lame gait characteristics based on time series
      accelerometer data.

PMID- 29324704
TI  - Dissection of Myogenic Differentiation Signatures in Chickens by RNA-Seq
      Analysis.
AB  - A series of elaborately regulated and orchestrated changes in gene expression
      profiles leads to muscle growth and development. In this study, RNA sequencing
      was used to profile embryonic chicken myoblasts and fused myotube transcriptomes,
      long non-coding RNAs (lncRNAs), and messenger RNAs (mRNAs) at four stages of
      myoblast differentiation. Of a total of 2484 lncRNA transcripts, 2288 were long
      intergenic non-coding RNAs (lincRNAs) and 198 were antisense lncRNAs.
      Additionally, 1530 lncRNAs were neighboring 2041 protein-coding genes (<10 kb
      upstream and downstream) and functionally enriched in several pathways related to
      skeletal muscle development that have been extensively studied, indicating that
      these genes may be in cis-regulatory relationships. In addition, Pearson's
      correlation coefficients demonstrated that 990 lncRNAs and 7436 mRNAs were
      possibly in trans-regulatory relationships. These co-expressed mRNAs were
      enriched in various developmentally-related biological processes, such as myocyte
      proliferation and differentiation, myoblast differentiation, and myoblast fusion.
      The number of transcripts (906 lncRNAs and 4422 mRNAs) differentially expressed
      across various stages declined with the progression of differentiation. Then,
      4422 differentially expressed genes were assigned to four clusters according to K
      means analysis. Genes in the K1 cluster likely play important roles in myoblast
      proliferation and those in the K4 cluster were likely associated with the
      initiation of myoblast differentiation, while genes in the K2 and K3 clusters
      were likely related to myoblast fusion. This study provides a catalog of chicken
      lncRNAs and mRNAs for further experimental investigations and facilitates a
      better understanding of skeletal muscle development.

PMID- 29324702
TI  - Listeria monocytogenes: The Impact of Cell Death on Infection and Immunity.
AB  - Listeria monocytogenes has evolved exquisite mechanisms for invading host cells
      and spreading from cell-to-cell to ensure maintenance of its intracellular
      lifecycle. As such, it is not surprising that loss of the intracellular
      replication niche through induction of host cell death has significant
      implications on the development of disease and the subsequent immune response.
      Although L. monocytogenes can activate multiple pathways of host cell death,
      including necrosis, apoptosis, and pyroptosis, like most intracellular pathogens
      L. monocytogenes has evolved a series of adaptations that minimize host cell
      death to promote its virulence. Understanding how L. monocytogenes modulates cell
      death during infection could lead to novel therapeutic approaches. In addition,
      as L. monocytogenes is currently being developed as a tumor immunotherapy
      platform, understanding how cell death pathways influence the priming and quality
      of cell-mediated immunity is critical. This review will focus on the mechanisms
      by which L. monocytogenes modulates cell death, as well as the implications of
      cell death on acute infection and the generation of adaptive immunity.

PMID- 29324705
TI  - Influence of Chitosan Treatment on Surrogate Serum Markers of Cholesterol
      Metabolism in Obese Subjects.
AB  - Chitosan treatment results in significantly lower serum low density lipoprotein
      (LDL) cholesterol concentrations. To assess the working mechanisms of chitosan,
      we measured serum surrogate markers of cholesterol absorption (campesterol,
      sitosterol, cholestanol), synthesis (lathosterol, lanosterol, desmosterol), and
      degradation to bile acids (7alpha-hydroxy-cholesterol, 27-hydroxy-cholesterol),
      corrected for cholesterol concentration (R_sterols). Over 12 weeks, 116 obese
      subjects (Body Mass Index, BMI 31.7, range 28.1-38.9 kg/m2) were studied under
      chitosan (n = 61) and placebo treatments (n = 55). The participants were briefly
      educated regarding improvement of nutrition quality and energy expenditure. Daily
      chitosan intake was 3200 mg. Serum LDL cholesterol concentration decreased
      significantly more (p = 0.0252) under chitosan (-8.67 +/- 18.18 mg/dL, 5.6%) than
      under placebo treatment (-1.00 +/- 24.22 mg/dL, 0.9%). This reduction was not
      associated with the expected greater decreases in markers of cholesterol
      absorption under chitosan treatment. Also, increases in markers of cholesterol
      synthesis and bile acid synthesis under chitosan treatment were not any greater
      than under placebo treatment. In conclusion, a significant selective reduction of
      serum LDL cholesterol under chitosan treatment is neither associated with a
      reduction of serum surrogate markers of cholesterol absorption, nor with
      increases of markers for cholesterol and bile acid synthesis.

PMID- 29324707
TI  - Evaluation of Controlled Release Urea on the Dynamics of Nitrate, Ammonium, and
      Its Nitrogen Release in Black Soils of Northeast China.
AB  - Controlled release urea (CRU) is considered to enhance crop yields while
      alleviating negative environmental problems caused by the hazardous gas emissions
      that are associated with high concentrations of ammonium (NH4+) and nitrate (NO3
      ) in black soils. Short-term effects of sulfur-coated urea (SCU) and polyurethane
      coated urea (PCU), compared with conventional urea, on NO3- and NH4+ in black
      soils were studied through the buried bag experiment conducted in an artificial
      climate chamber. We also investigated nitrogen (N) release kinetics of CRU and
      correlations between the cumulative N release rate and concentrations of NO3- and
      NH4+. CRU can reduce concentrations of NO3- and NH4+, and PCU was more effective
      in maintaining lower soil NO3-/NH4+ ratios than SCU and U. Parabolic equation
      could describe the kinetics of NO3- and NH4+ treated with PCU. The Elovich
      equation could describe the kinetics of NO3- and NH4+ treated with SCU. The
      binary linear regression model was established to predict N release from PCU
      because of significant correlations between the cumulative N release rate and
      concentrations of NO3- and NH4+. These results provided a methodology and data
      support for characterizing and predicting the N release from PCU in black soils.

PMID- 29324708
TI  - Golay Complementary Waveforms in Reed-Muller Sequences for Radar Detection of
      Nonzero Doppler Targets.
AB  - Golay complementary waveforms can, in theory, yield radar returns of high range
      resolution with essentially zero sidelobes. In practice, when deployed
      conventionally, while high signal-to-noise ratios can be achieved for static
      target detection, significant range sidelobes are generated by target returns of
      nonzero Doppler causing unreliable detection. We consider signal processing
      techniques using Golay complementary waveforms to improve radar detection
      performance in scenarios involving multiple nonzero Doppler targets. A signal
      processing procedure based on an existing, so called, Binomial Design algorithm
      that alters the transmission order of Golay complementary waveforms and weights
      the returns is proposed in an attempt to achieve an enhanced illumination
      performance. The procedure applies one of three proposed waveform transmission
      ordering algorithms, followed by a pointwise nonlinear processor combining the
      outputs of the Binomial Design algorithm and one of the ordering algorithms. The
      computational complexity of the Binomial Design algorithm and the three ordering
      algorithms are compared, and a statistical analysis of the performance of the
      pointwise nonlinear processing is given. Estimation of the areas in the Delay
      Doppler map occupied by significant range sidelobes for given targets are also
      discussed. Numerical simulations for the comparison of the performances of the
      Binomial Design algorithm and the three ordering algorithms are presented for
      both fixed and randomized target locations. The simulation results demonstrate
      that the proposed signal processing procedure has a better detection performance
      in terms of lower sidelobes and higher Doppler resolution in the presence of
      multiple nonzero Doppler targets compared to existing methods.

PMID- 29324709
TI  - Perpendicular Magnetic Anisotropy in Heusler Alloy Films and Their
      Magnetoresistive Junctions.
AB  - For the sustainable development of spintronic devices, a half-metallic
      ferromagnetic film needs to be developed as a spin source with exhibiting 100%
      spin polarisation at its Fermi level at room temperature. One of the most
      promising candidates for such a film is a Heusler-alloy film, which has already
      been proven to achieve the half-metallicity in the bulk region of the film. The
      Heusler alloys have predominantly cubic crystalline structures with small
      magnetocrystalline anisotropy. In order to use these alloys in perpendicularly
      magnetised devices, which are advantageous over in-plane devices due to their
      scalability, lattice distortion is required by introducing atomic substitution
      and interfacial lattice mismatch. In this review, recent development in
      perpendicularly-magnetised Heusler-alloy films is overviewed and their
      magnetoresistive junctions are discussed. Especially, focus is given to binary
      Heusler alloys by replacing the second element in the ternary Heusler alloys with
      the third one, e.g., MnGa and MnGe, and to interfacially-induced anisotropy by
      attaching oxides and metals with different lattice constants to the Heusler
      alloys. These alloys can improve the performance of spintronic devices with
      higher recording capacity.

PMID- 29324710
TI  - The Intention to be Physically Active in Sedentary Obese Children: A Longitudinal
      Study.
AB  - Obese children are usually less active than their normal-weight counterparts,
      although the reasons for this remain unclear. The objective of the present study
      was to determine how a long-term program (3 years of intervention and 6 months of
      follow-up detraining) of physical exercise with or without a low calorie diet
      influenced sedentary obese children's intention to be physically active. The
      participants were 27 children, ages from 8 to 11 years, who formed two groups
      according to the program that they followed. One group followed an exercise
      program (three 90-min sessions per week), and the other this same exercise
      program together with a hypocaloric diet. The intention to be physically active
      was assessed via the Measurement of Intention to be Physically Active (MIFA)
      questionnaire. The subjects' scores at different times of the program (baseline,
      Year 3, and detraining) were compared using a repeated-measures ANOVA, and a post
      hoc Tukey's test was applied to confirm the differences. After both the
      intervention and detraining, both groups showed greater intention to be
      physically active. This suggests the suitability of long-term physical exercise
      to generate greater intention to be physically active and thus establish healthy
      life habits including increased levels of physical activity.

PMID- 29324711
TI  - The Investigation of the Waveguiding Properties of Silk Fibroin from the Visible
      to Near-Infrared Spectrum.
AB  - Silk fibroin protein has been reinvented as a new optical material for
      biophotonic applications because of its optical transparency, biocompatibility,
      and easy fabrication process. It is used in various silk-based optical devices,
      which makes it desirable to investigate the optical properties of silk from
      diverse perspectives. This paper presents our investigation of the optical
      properties of silk fibroin, extracted from Bombyx mori cocoons. We have measured
      transmission spectra from the visible to near-infrared region and investigated
      waveguiding properties by the prism-coupling technique for five wavelengths
      (473.0, 632.8, 964.0, 1311, and 1552 nm). From the measurements, we determined
      the values of refractive indices. The measurements also proved waveguiding
      properties for all of the wavelengths. Optical scattering losses were measured by
      the fiber probe technique at 632.8 nm and were estimated to be 0.22 dB.cm-1.

PMID- 29324712
TI  - Positron Spectroscopy of Nanodiamonds after Hydrogen Sorption.
AB  - The structure and defects of nanodiamonds influence the hydrogen sorption
      capacity. Positronium can be used as a sensor for detecting places with the most
      efficient capture of hydrogen atoms. Hydrogenation of carbon materials was
      performed from gas atmosphere. The concentration of hydrogen absorbed by the
      sample depends on the temperature and pressure. The concentration 1.2 wt % is
      achieved at the temperature of 243 K and the pressure of 0.6 MPa. The hydrogen
      saturation of nanodiamonds changes the positron lifetime. Increase of sorption
      cycle numbers effects the positron lifetime, as well as the parameters of the
      Doppler broadening of annihilation line. The electron-positron annihilation being
      a sensitive method, it allows detecting the electron density fluctuation of the
      carbon material after hydrogen saturation.

PMID- 29324713
TI  - Asymmetric Conjugate Addition of alpha,alpha-Disubstituted Aldehydes to
      Nitroalkenes Organocatalyzed by Chiral Monosalicylamides from trans-Cyclohexane
      1,2-Diamines.
AB  - Primary amine-salicylamides derived from chiral trans-cyclohexane-1,2-diamines
      are used as organocatalysts for the enantioselective conjugate addition of
      alpha,alpha-disubstituted aldehydes to arylated and heteroarylated nitroalkenes.
      The reaction is performed in the presence of 4-dimethylaminopyridine as an
      additive in dichloromethane as a solvent at room temperature. The corresponding
      enantioenriched gamma-nitroaldehydes are obtained with enantioselectivities up to
      95%. Theoretical calculations are used to justify the reasons of the
      stereoinduction.

PMID- 29324714
TI  - Determination of Branched-Chain Keto Acids in Serum and Muscles Using High
      Performance Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry.
AB  - Branched-chain keto acids (BCKAs) are derivatives from the first step in the
      metabolism of branched-chain amino acids (BCAAs) and can provide important
      information on animal health and disease. Here, a simple, reliable and effective
      method was developed for the determination of three BCKAs (alpha-ketoisocaproate,
      alpha-keto-beta-methylvalerate and alpha-ketoisovalerate) in serum and muscle
      samples using high performance liquid chromatography-quadrupole time-of-flight
      mass spectrometry (HPLC-Q-TOF/MS). The samples were extracted using methanol and
      separated on a 1.8 MUm Eclipse Plus C18 column within 10 min. The mobile phase
      was 10 mmol L-1 ammonium acetate aqueous solution and acetonitrile. The results
      showed that recoveries for the three BCKAs ranged from 78.4% to 114.3% with
      relative standard deviation (RSD) less than 9.7%. The limit of quantitation (LOQ)
      were 0.06~0.23 MUmol L-1 and 0.09~0.27 nmol g-1 for serum and muscle samples,
      respectively. The proposed method can be applied to the determination of three
      BCKAs in animal serum and muscle samples.

PMID- 29324706
TI  - Endothelial Ca2+ Signaling and the Resistance to Anticancer Treatments: Partners
      in Crime.
AB  - Intracellular Ca2+ signaling drives angiogenesis and vasculogenesis by
      stimulating proliferation, migration, and tube formation in both vascular
      endothelial cells and endothelial colony forming cells (ECFCs), which represent
      the only endothelial precursor truly belonging to the endothelial phenotype. In
      addition, local Ca2+ signals at the endoplasmic reticulum (ER)-mitochondria
      interface regulate endothelial cell fate by stimulating survival or apoptosis
      depending on the extent of the mitochondrial Ca2+ increase. The present article
      aims at describing how remodeling of the endothelial Ca2+ toolkit contributes to
      establish intrinsic or acquired resistance to standard anti-cancer therapies. The
      endothelial Ca2+ toolkit undergoes a major alteration in tumor endothelial cells
      and tumor-associated ECFCs. These include changes in TRPV4 expression and
      increase in the expression of P2X7 receptors, Piezo2, Stim1, Orai1, TRPC1, TRPC5,
      Connexin 40 and dysregulation of the ER Ca2+ handling machinery. Additionally,
      remodeling of the endothelial Ca2+ toolkit could involve nicotinic acetylcholine
      receptors, gasotransmitters-gated channels, two-pore channels and Na+/H+
      exchanger. Targeting the endothelial Ca2+ toolkit could represent an alternative
      adjuvant therapy to circumvent patients' resistance to current anti-cancer
      treatments.

PMID- 29324715
TI  - Nitrogen-Doped Diamond Film for Optical Investigation of Hemoglobin
      Concentration.
AB  - In this work we present the fabrication and characterization of a diamond film
      which can be utilized in the construction of optical sensors for the
      investigation of biological samples. We produced a nitrogen-doped diamond (NDD)
      film using a microwave plasma enhanced chemical vapor deposition (MWPECVD)
      system. The NDD film was investigated with the use of scanning electron
      microscopy (SEM), atomic force microscopy (AFM) and Raman spectroscopy. The NDD
      film was used in the construction of the fiber optic sensor. This sensor is based
      on the Fabry-Perot interferometer working in a reflective mode and the NDD film
      is utilized as a reflective layer of this interferometer. Application of the NDD
      film allowed us to obtain the sensor of hemoglobin concentration with linear work
      characteristics with a correlation coefficient (R2) equal to 0.988.

PMID- 29324716
TI  - The Effects of a Macromolecular Charring Agent with Gas Phase and Condense Phase
      Synergistic Flame Retardant Capability on the Properties of PP/IFR Composites.
AB  - In order to improve the efficiency of intumescent flame retardants (IFRs), a
      novel macromolecular charring agent named poly(ethanediamine-1,3,5-triazine-p-4
      amino-2,2,6,6-tetramethylpiperidine) (PETAT) with gas phase and condense phase
      synergistic flame-retardant capability was synthesized and subsequently dispersed
      into polypropylene (PP) in combination with ammonium polyphosphate (APP) via a
      melt blending method. The chemical structure of PETAT was investigated by Fourier
      transform infrared spectroscopy (FTIR), and 1H nuclear magnetic resonance (NMR)
      spectroscopy. Thermal properties of the PETAT and IFR systems were tested by
      thermogravimetric-derivative thermogravimetric analysis (TGA-DTG) and
      thermogravimetry-Fourier transform infrared spectroscopy (TG-FTIR). The
      mechanical properties, thermal stability, flame-retardant properties, water
      resistance, and structures of char residue in flame-retardant composites were
      characterized using tensile and flexural strength property tests, TGA, limiting
      oxygen index (LOI) values before and after soaking, underwritten laboratory-94
      (UL-94) vertical burning test, cone calorimetric test (CCT), scanning electron
      microscopy with energy dispersive X-ray spectrometry (SEM-EDXS), and FTIR. The
      results indicated that PETAT was successfully synthesized, and when the ratio of
      APP to PETAT was 2:1 with 25 wt % loading, the novel IFR system could reduce the
      deterioration of tensile strength and enhance the flexural strength of
      composites. Meanwhile, the flame-retardant composite was able to pass the UL-94 V
      0 rating with an LOI value of 30.3%, and the peak of heat release rate (PHRR),
      total heat release (THR), and material fire hazard values were considerably
      decreased compared with others. In addition, composites also exhibited excellent
      water resistance properties compared with traditional IFR composites. SEM-EDXS
      and FTIR analyses of the char residues, as well as TG-FTIR analyses of IFR were
      used to investigate the flame-retardant mechanism of the APP/PETAT IFR system.
      The results indicated that the efficient flame retardancy of PP/IFR composites
      could be attributed to the synergism of the free radical-quenching and char layer
      protecting mechanisms in the gas phase and condense phase, respectively.

PMID- 29324717
TI  - Residual Inequity: Assessing the Unintended Consequences of New York City's Clean
      Heat Transition.
AB  - Energy policies and public health are intimately intertwined. In New York City, a
      series of policies, known as the Clean Heat Program (CHP), were designed to
      reduce air pollution by banning residual diesel fuel oils, #6 in 2015 and #4 by
      2030. This measure is expected to yield environmental and public health benefits
      over time. While there is near-universal compliance with the #6 ban, a
      substantial number of buildings still use #4. In this paper, geographic analysis
      and qualitative interviews with stakeholders were used to interrogate the CHP's
      policy implementation in Northern Manhattan and the Bronx. A total of 1724 (53%)
      of all residential residual fuel burning buildings are located in this region.
      Stakeholders reflected mostly on the need for the program, and overall reactions
      to its execution. Major findings include that government partnerships with non
      governmental organizations were effectively employed. However, weaknesses with
      the policy were also identified, including missed opportunities for more rapid
      transitions away from residual fuels, unsuccessful outreach efforts, cost
      prohibitive conversion opportunities, and (the perception of) a volatile energy
      market for clean fuels. Ultimately, this analysis serves as a case study of a
      unique and innovative urban policy initiative to improve air quality and,
      consequently, public health.

PMID- 29324719
TI  - An Enhanced Secure Identity-Based Certificateless Public Key Authentication
      Scheme for Vehicular Sensor Networks.
AB  - Vehicular sensor networks have been widely applied in intelligent traffic systems
      in recent years. Because of the specificity of vehicular sensor networks, they
      require an enhanced, secure and efficient authentication scheme. Existing
      authentication protocols are vulnerable to some problems, such as a high
      computational overhead with certificate distribution and revocation, strong
      reliance on tamper-proof devices, limited scalability when building many secure
      channels, and an inability to detect hardware tampering attacks. In this paper,
      an improved authentication scheme using certificateless public key cryptography
      is proposed to address these problems. A security analysis of our scheme shows
      that our protocol provides an enhanced secure anonymous authentication, which is
      resilient against major security threats. Furthermore, the proposed scheme
      reduces the incidence of node compromise and replication attacks. The scheme also
      provides a malicious-node detection and warning mechanism, which can quickly
      identify compromised static nodes and immediately alert the administrative
      department. With performance evaluations, the scheme can obtain better trade-offs
      between security and efficiency than the well-known available schemes.

PMID- 29324718
TI  - Screening of E. coli beta-clamp Inhibitors Revealed that Few Inhibit Helicobacter
      pylori More Effectively: Structural and Functional Characterization.
AB  - The characteristic of interaction with various enzymes and processivity-promoting
      nature during DNA replication makes beta-clamp an important drug target.
      Helicobacter pylori (H. pylori) have several unique features in DNA replication
      machinery that makes it different from other microorganisms. To find out whether
      difference in DNA replication proteins behavior accounts for any difference in
      drug response when compared to E. coli, in the present study, we have tested E.
      coli beta-clamp inhibitor molecules against H. pylori beta-clamp. Various
      approaches were used to test the binding of inhibitors to H. pylori beta-clamp
      including docking, surface competition assay, complex structure determination, as
      well as antimicrobial assay. Out of five shortlisted inhibitor molecules on the
      basis of docking score, three molecules, 5-chloroisatin, carprofen, and 3,4
      difluorobenzamide were co-crystallized with H. pylori beta-clamp and the
      structures show that they bind at the protein-protein interaction site as
      expected. In vivo studies showed only two molecules, 5-chloroisatin, and 3,4
      difluorobenzamide inhibited the growth of the pylori with MIC values in micro
      molar range, which is better than the inhibitory effect of the same drugs on E.
      coli. Therefore, the evaluation of such drugs against H. pylori may explore the
      possibility to use to generate species-specific pharmacophore for development of
      new drugs against H. pylori.

PMID- 29324721
TI  - Electromagnetic Acoustic Transducers for Robotic Nondestructive Inspection in
      Harsh Environments.
AB  - Elevated temperature, gamma radiation, and geometric constraints inside dry
      storage casks for spent nuclear fuel represent a harsh environment for
      nondestructive inspection of the cask and require that the inspection be
      conducted with a robotic system. Electromagnetic acoustic transducers (EMATs)
      using non-contact ultrasonic transduction based on the Lorentz force to
      excite/receive ultrasonic waves are suited for use in the robotic inspection.
      Periodic permanent magnet EMATs that actuate/receive shear horizontal guided
      waves are developed for application to robotic nondestructive inspection of
      stress corrosion cracks in the heat affected zone of welds in stainless steel dry
      storage canisters. The EMAT's components are carefully selected in consideration
      of the inspection environment, and tested under elevated temperature and gamma
      radiation doses up to 177  degrees C and 5920 krad, respectively, to evaluate the
      performance of the EMATs under realistic environmental conditions. The effect of
      gamma radiation is minimal, but the EMAT's performance is affected by
      temperatures above 121  degrees C due to the low Curie temperature of the
      magnets. Different magnets are needed to operate at 177  degrees C. The EMAT's
      capability to detect notches is also evaluated from B-scan measurements on 304
      stainless steel welded plate containing surface-breaking notches.

PMID- 29324720
TI  - Biointeractions of Herbicide Atrazine with Human Serum Albumin: UV-Vis,
      Fluorescence and Circular Dichroism Approaches.
AB  - The herbicide atrazine is widely used across the globe, which is a great concern.
      To investigate its potential toxicity in the human body, human serum albumin
      (HSA) was selected as a model protein. The interaction between atrazine and HSA
      was investigated using steady-state fluorescence spectroscopy, synchronous
      fluorescence spectroscopy, UV-Vis spectroscopy, three-dimensional (3D)
      fluorescence spectroscopy and circular dichroism (CD) spectroscopy. The intrinsic
      fluorescence of HSA was quenched by the atrazine through a static quenching
      mechanism. Fluorescence spectra at two excitation wavelengths (280 and 295 nm)
      showed that the fluorescence quenched in HSA was mainly contributed to by
      tryptophan residues. In addition, the atrazine bound to HSA, which induced
      changes in the conformation and secondary structure of HSA and caused an energy
      transfer. Thermodynamic parameters revealed that this binding is spontaneous.
      Moreover, electrostatic interactions play a major role in the combination of
      atrazine and HSA. One atrazine molecule can only bind to one HSA molecule to form
      a complex, and the atrazine molecule is bound at site II (subdomain IIIA) of HSA.
      This study furthers the understanding of the potential effects posed by atrazine
      on humans at the molecular level.

PMID- 29324723
TI  - Error Recovery in the Time-Triggered Paradigm with FTT-CAN.
AB  - Data networks are naturally prone to interferences that can corrupt messages,
      leading to performance degradation or even to critical failure of the
      corresponding distributed system. To improve resilience of critical systems, time
      triggered networks are frequently used, based on communication schedules defined
      at design-time. These networks offer prompt error detection, but slow error
      recovery that can only be compensated with bandwidth overprovisioning. On the
      contrary, the Flexible Time-Triggered (FTT) paradigm uses online traffic
      scheduling, which enables a compromise between error detection and recovery that
      can achieve timely recovery with a fraction of the needed bandwidth. This article
      presents a new method to recover transmission errors in a time-triggered
      Controller Area Network (CAN) network, based on the Flexible Time-Triggered
      paradigm, namely FTT-CAN. The method is based on using a server (traffic shaper)
      to regulate the retransmission of corrupted or omitted messages. We show how to
      design the server to simultaneously: (1) meet a predefined reliability goal, when
      considering worst case error recovery scenarios bounded probabilistically by a
      Poisson process that models the fault arrival rate; and, (2) limit the direct and
      indirect interference in the message set, preserving overall system
      schedulability. Extensive simulations with multiple scenarios, based on practical
      and randomly generated systems, show a reduction of two orders of magnitude in
      the average bandwidth taken by the proposed error recovery mechanism, when
      compared with traditional approaches available in the literature based on adding
      extra pre-defined transmission slots.

PMID- 29324722
TI  - Evaluation of a New Survivin ELISA and UBC(r) Rapid for the Detection of Bladder
      Cancer in Urine.
AB  - Urine-based biomarkers for non-invasive diagnosis of bladder cancer are urgently
      needed. No single marker with sufficient sensitivity and specificity has been
      described so far. Thus, a combination of markers appears to be a promising
      approach. The aim of this case-control study was to evaluate the performance of
      an in-house developed enzyme-linked immunosorbent assay (ELISA) for survivin, the
      UBC(r)Rapid test, and the combination of both assays. A total of 290 patients
      were recruited. Due to prior bladder cancer, 46 patients were excluded. Urine
      samples were available from 111 patients with bladder cancer and 133 clinical
      controls without urologic diseases. Antibodies generated from recombinant
      survivin were utilized to develop a sandwich ELISA. The ELISA and the UBC(r)Rapid
      test were applied to all urine samples. Receiver operating characteristic (ROC)
      analysis was used to evaluate marker performance. The survivin ELISA exhibited a
      sensitivity of 35% with a specificity of 98%. The UBC(r)Rapid test showed a
      sensitivity of 56% and a specificity of 96%. Combination of both assays increased
      the sensitivity to 66% with a specificity of 95%. For high-grade tumors, the
      combination showed a sensitivity of 82% and a specificity of 95%. The new
      survivin ELISA and the UBC(r)Rapid test are both able to detect bladder cancer,
      especially high-grade tumors. However, the performance of each individual marker
      is moderate and efforts to improve the survivin assay should be pursued. A
      combination of both assays confirmed the benefit of using marker panels. The
      results need further testing in a prospective study and with a high-risk
      population.

PMID- 29324725
TI  - West Nile Virus and Other Nationally Notifiable Arboviral Diseases - United
      States, 2016.
AB  - Arthropod-borne viruses (arboviruses) are transmitted to humans primarily through
      the bites of infected mosquitoes and ticks. West Nile virus (WNV) is the leading
      cause of domestically acquired arboviral disease in the continental United States
      (1,2). Other arboviruses, including La Crosse, Powassan, Jamestown Canyon, St.
      Louis encephalitis, and eastern equine encephalitis viruses, cause sporadic cases
      of disease and occasional outbreaks. This report summarizes surveillance data
      reported to CDC for 2016 for nationally notifiable arboviruses. It excludes
      dengue, chikungunya, and Zika viruses, as these are primarily nondomestic viruses
      typically acquired through travel. Forty-seven states and the District of
      Columbia (DC) reported 2,240 cases of domestic arboviral disease, including 2,150
      (96%) WNV disease cases. Of the WNV disease cases, 1,310 (61%) were classified as
      neuroinvasive disease (e.g., meningitis, encephalitis, acute flaccid paralysis),
      for a national incidence of 0.41 cases per 100,000 population. After WNV, the
      most frequently reported arboviruses were La Crosse (35 cases), Powassan (22),
      and Jamestown Canyon (15) viruses. Because arboviral diseases continue to cause
      serious illness, maintaining surveillance is important to direct prevention
      activities.

PMID- 29324724
TI  - Evaluation of Oxidative Stress Levels and Antioxidant Enzyme Activities in Burst
      Fractures.
AB  - BACKGROUND Spinal burst fractures are pathologies that occur in spinal injuries
      and cause significant mortality and morbidity as a result. Burst fractures in
      spinal cord injuries can result in rapid and significant oxidative stress. In
      addition to the primary injury in severe spinal cord injuries, subsequent
      secondary lesions are mainly due to inflammatory cascade activation and excessive
      production of free radicals. This study evaluated oxidative stress and
      antioxidant enzyme levels in burst fractures. MATERIAL AND METHODS Twenty
      patients with burst fractures were diagnosed and underwent surgery and 20 healthy
      control subjects were included in the study. Neurological status was evaluated
      using the American Spine Injury Association Impairment Scale (ASIA) before and
      after surgery. Neurological function was scored as ASIA A: complete deficits,
      ASIA B-D: incomplete deficits, and ASIA E: neurologically intact.
      Spectrophotometry was performed to measure malondialdehyde (MDA) and low
      glutathione (GSH), glutathione peroxidase (GPx) levels, which represent lipid
      peroxide content. Evaluations were performed within 2 days after injury in the
      patients. RESULTS MDA levels were higher in the burst fracture group (p<0.001),
      whereas GSH and SOD activities were higher in the control group (both p<0.001).
      There was no statistically significant difference in GPx levels between the
      groups (p=0.482). CONCLUSIONS Oxidative stress appears to be related to burst
      fractures. Considering the importance of burst fractures in spinal cord injuries,
      a better understanding of these mechanisms may help in defining the role of
      oxidative stress after burst fractures. Prospective, randomized, controlled
      trials may reveal new therapeutic approaches that include antioxidants for
      explosive fractures focusing on oxidative stress.

PMID- 29324726
TI  - HIV Infection and HIV-Associated Behaviors Among Persons Who Inject Drugs - 20
      Cities, United States, 2015.
AB  - In the United States, 9% of human immunodeficiency virus (HIV) infections
      diagnosed in 2015 were attributed to injection drug use (1). In 2015, 79% of
      diagnoses of HIV infection among persons who inject drugs occurred in urban areas
      (2). To monitor the prevalence of HIV infection and associated behaviors among
      persons who inject drugs, CDC's National HIV Behavioral Surveillance (NHBS)
      conducts interviews and HIV testing in selected metropolitan statistical areas
      (MSAs) (3). The prevalence of HIV infection among persons who inject drugs in 20
      MSAs in 2015 was 7%. In a behavioral analysis of HIV-negative persons who inject
      drugs, an estimated 27% receptively shared syringes and 67% had condomless
      vaginal sex in the previous 12 months. During the same period, 58% had tested for
      HIV infection and 52% received syringes from a syringe services program. Given
      the increased number of persons newly injecting drugs who are at risk for HIV
      infection because of the recent opioid epidemic (2,4), these findings underscore
      the importance of continuing and expanding health services, HIV prevention
      programs, and community-based strategies, such as those provided by syringe
      services programs, for this population.

PMID- 29324727
TI  - Frequent Exertion and Frequent Standing at Work, by Industry and Occupation Group
      - United States, 2015.
AB  - Repeated exposure to occupational ergonomic hazards, such as frequent exertion
      (repetitive bending or twisting) and frequent standing, can lead to injuries,
      most commonly musculoskeletal disorders (1). Work-related musculoskeletal
      disorders have been estimated to cost the United States approximately $2.6
      billion in annual direct and indirect costs (2). A recent literature review
      provided evidence that prolonged standing at work also leads to adverse health
      outcomes, such as back pain, physical fatigue, and muscle pain (3). To determine
      which industry and occupation groups currently have the highest prevalence rates
      of frequent exertion at work and frequent standing at work, CDC analyzed data
      from the 2015 National Health Interview Survey (NHIS) Occupational Health
      Supplement (OHS) regarding currently employed adults in the United States. By
      industry, the highest prevalence of both frequent exertion and frequent standing
      at work was among those in the agriculture, forestry, fishing, and hunting
      industry group (70.9%); by occupation, the highest prevalence was among those in
      the construction and extraction occupation group (76.9%). Large differences among
      industry and occupation groups were found with regard to these ergonomic hazards,
      suggesting a need for targeted interventions designed to reduce workplace
      exposure.

PMID- 29324728
TI  - Recommendation of the Advisory Committee on Immunization Practices for Use of a
      Third Dose of Mumps Virus-Containing Vaccine in Persons at Increased Risk for
      Mumps During an Outbreak.
AB  - A substantial increase in the number of mumps outbreaks and outbreak-associated
      cases has occurred in the United States since late 2015 (1,2). To address this
      public health problem, the Advisory Committee on Immunization Practices (ACIP)
      reviewed the available evidence and determined that a third dose of measles,
      mumps, rubella (MMR) vaccine is safe and effective at preventing mumps. During
      its October 2017 meeting, ACIP recommended a third dose of a mumps virus
      containing vaccine* for persons previously vaccinated with 2 doses who are
      identified by public health authorities as being part of a group or population at
      increased risk for acquiring mumps because of an outbreak. The purpose of the
      recommendation is to improve protection of persons in outbreak settings against
      mumps disease and mumps-related complications. This recommendation supplements
      the existing ACIP recommendations for mumps vaccination (3).

PMID- 29324729
TI  - Vital Signs: Trends and Disparities in Infant Safe Sleep Practices - United
      States, 2009-2015.
AB  - INTRODUCTION: There have been dramatic improvements in reducing infant sleep
      related deaths since the 1990s, when recommendations were introduced to place
      infants on their backs for sleep. However, there are still approximately 3,500
      sleep-related deaths among infants each year in the United States, including
      those from sudden infant death syndrome, accidental suffocation and strangulation
      in bed, and unknown causes. Unsafe sleep practices, including placing infants in
      a nonsupine (on side or on stomach) sleep position, bed sharing, and using soft
      bedding in the sleep environment (e.g., blankets, pillows, and soft objects) are
      modifiable risk factors for sleep-related infant deaths.

PMID- 29324730
TI  - QuickStats: Age-Adjusted Percentages* of Current Smokers? Among Adults Aged >=18
      Years, by Sex, Race, and Hispanic OriginS - National Health Interview Survey,
      2016 .
AB  - In 2016, men aged >=18 years were more likely to be current smokers than women
      (17.5% compared with 13.6%). Non-Hispanic black men (20.1%) and non-Hispanic
      white men (18.4%) were more likely to be current smokers than Hispanic men
      (13.8%). Non-Hispanic white women (16.2%) were more likely to be current smokers
      than non-Hispanic black women (13.2%) and Hispanic women (6.9%).

PMID- 29324731
TI  - Notice to Readers: Online Manuscript Submission System Now Available for MMWR
      Serial Publications.
AB  - The MMWR Serial Publications are now using ScholarOne Manuscripts, an online
      system for manuscript submissions. This system provides comprehensive workflow
      management and streamlines the submission process for Recommendations and
      Reports, Surveillance Summaries, and Supplements.

PMID- 29324732
TI  - Tobacco Product Use Among Military Veterans - United States, 2010-2015.
AB  - In 2015, an estimated 18.8 million U.S. adults were military veterans (1).
      Although the prevalence of tobacco-attributable conditions is high among veterans
      (2), there is a paucity of data on use of tobacco products, other than
      cigarettes, in this population. To monitor tobacco product use among veterans,
      CDC analyzed self-reported current (i.e., past 30-day) use of five tobacco
      product types (cigarettes, cigars [big cigars, cigarillos, or little cigars],
      roll-your-own tobacco, pipes, and smokeless tobacco [chewing tobacco, snuff, dip,
      or snus]) from the National Survey on Drug Use and Health (NSDUH). Overall, 29.2%
      of veterans reported current use of any of the assessed tobacco products.
      Cigarettes were the most commonly used tobacco product (21.6%), followed by
      cigars (6.2%), smokeless tobacco (5.2%), roll-your-own tobacco (3.0%), and pipes
      (1.5%); 7.0% of veterans currently used two or more tobacco products. Within
      subgroups of veterans, current use of any of the assessed tobacco products was
      higher among persons aged 18-25 years (56.8%), Hispanics (34.0%), persons with
      less than a high school diploma (37.9%), those with annual family income <$20,000
      (44.3%), living in poverty (53.7%), reporting serious psychological distress
      (48.2%), and with no health insurance (60.1%). By age and sex subgroups, use of
      any of the assessed tobacco products was significantly higher among all veteran
      groups than their nonveteran counterparts, except males aged >=50 years.
      Expanding the reach of evidence-based tobacco control interventions among
      veterans could reduce tobacco use prevalence in this population.

PMID- 29324733
TI  - Antibiotics Dispensed to Privately Insured Pregnant Women with Urinary Tract
      Infections - United States, 2014.
AB  - Urinary tract infections (UTIs) occur in about 8% of pregnant women, and
      untreated UTIs can have serious consequences, including pyelonephritis, preterm
      labor, low birth weight, and sepsis (1). Pregnant women are typically screened
      for UTIs during early pregnancy, and those with bacteriuria are treated with
      antibiotics (1,2). Antibiotic stewardship is critical to improving patient safety
      and to combating antibiotic resistance. Because of the potential risk for birth
      defects, including anencephaly, heart defects, and orofacial clefts, associated
      with use of sulfonamides and nitrofurantoin during pregnancy (3), a 2011
      committee opinion from the American College of Obstetricians and Gynecologists
      (ACOG) recommended that sulfonamides and nitrofurantoin may be prescribed in the
      first trimester of pregnancy only when other antimicrobial therapies are deemed
      clinically inappropriate (4). To assess the effects of these recommendations, CDC
      analyzed the Truven Health MarketScan Commercial Database* to examine antibiotic
      prescriptions filled by pregnant women with UTIs. Among 482,917 pregnancies in
      2014, 7.2% of women had an outpatient UTI diagnosis during the 90 days before the
      date of last menstrual period (LMP) or during pregnancy. Among pregnant women
      with UTIs, the most frequently prescribed antibiotics during the first trimester
      were nitrofurantoin, ciprofloxacin, cephalexin, and trimethoprim
      sulfamethoxazole. Given the potential risks associated with use of some of these
      antibiotics in early pregnancy and the potential for unrecognized pregnancy,
      women's health care providers should be familiar with the ACOG recommendations
      and consider the possibility of early pregnancy when treating women of
      reproductive age.

PMID- 29324734
TI  - Notice to Readers: New Web Location for Weekly and Annual NNDSS Data.
AB  - To improve the usability, availability, quality, and timeliness of surveillance
      data as part of the CDC Surveillance Strategy (1), CDC now provides users a
      convenient way to access notifiable infectious and noninfectious disease data
      through the National Notifiable Diseases Surveillance System (NNDSS) website.

PMID- 29324736
TI  - No additional prognostic value for MRE11 in squamous cell carcinomas of the anus
      treated with chemo-radiotherapy.
AB  - This corrects the article DOI: 10.1038/bjc.2017.188.

PMID- 29324735
TI  - Influence of c-Src on hypoxic resistance to paclitaxel in human ovarian cancer
      cells and reversal of FV-429.
AB  - SRC family kinase was documented to have vital roles in adjusting cancer cell
      malignant behaviors. To date, the role of c-Src, a member of SRC family kinase,
      in resistance to paclitaxel in human ovarian cancer cells under hypoxia has not
      been investigated. In the present study, we discovered that hypoxic environment
      suppressed paclitaxel-induced G2/M phase arrest and blockade of c-Src improved
      ovarian cancer cells' sensitivity to paclitaxel. FV-429, a derivative of natural
      flavonoid wogonin, could suppress gene expression and activation of c-Src,
      followed by deteriorated Stat3 nuclear translocation and its binding to HIF
      1alpha, resulting in paclitaxel resistance reversal through G2/M arrest
      potentiation. Our study demonstrated that c-Src contributed to hypoxic
      microenvironment-rendered paclitaxel resistance in human epithelial ovarian
      cancer cells by G2/M phase arrest deterioration, and through c-Src suppression,
      FV-429 was capable of reversing the resistance by blocking c-Src/Stat3/HIF-1alpha
      pathway.

PMID- 29324737
TI  - Barriers of attendance to dog rabies static point vaccination clinics in
      Blantyre, Malawi.
AB  - Rabies is a devastating yet preventable disease that causes around 59,000 human
      deaths annually. Almost all human rabies cases are caused by bites from rabies
      infected dogs. A large proportion of these cases occur in Sub Saharan Africa
      (SSA). Annual vaccination of at least 70% of the dog population is recommended by
      the World Health Organisation in order to eliminate rabies. However, achieving
      such high vaccination coverage has proven challenging, especially in low resource
      settings. Despite being logistically and economically more feasible than door-to
      door approaches, static point (SP) vaccination campaigns often suffer from low
      attendance and therefore result in low vaccination coverage. Here, we
      investigated the barriers to attendance at SP offering free rabies vaccinations
      for dogs in Blantyre, Malawi. We analysed data for 22,924 dogs from a city-wide
      vaccination campaign in combination with GIS and household questionnaire data
      using multivariable logistic regression and distance estimation techniques. We
      found that distance plays a crucial role in SP attendance (i.e. for every km
      closer the odds of attending a SP point are 3.3 times higher) and that very few
      people are willing to travel more than 1.5 km to bring their dog for vaccination.
      Additionally, we found that dogs from areas with higher proportions of people
      living in poverty are more likely to be presented for vaccination (ORs 1.58
      2.22). Furthermore, puppies (OR 0.26), pregnant or lactating female dogs (OR
      0.60) are less likely to be presented for vaccination. Owners also reported that
      they did not attend an SP because they were not aware of the campaign (27%) or
      they could not handle their dog (19%). Our findings will inform the design of
      future rabies vaccination programmes in SSA which may lead to improved
      vaccination coverage achieved by SP alone.

PMID- 29324738
TI  - Population structure analysis of the neglected parasite Thelazia callipaeda
      revealed high genetic diversity in Eastern Asia isolates.
AB  - BACKGROUND: Thelazia callipaeda is the causative agent of thelaziasis in canids,
      felids and humans. However, the population genetic structure regarding this
      parasite remains unclear. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we first
      explored the genetic variation of 32 T. callipaeda clinical isolates using the
      following multi-molecular markers: cox1, cytb, 12S rDNA, ITS1 and 18S rDNA. The
      isolates were collected from 13 patients from 11 geographical locations in China.
      Next, the population structure of T. callipaeda from Europe and other Asian
      countries was analyzed using the cox1 sequences collected during this study and
      from the GenBank database. In general, the Chinese clinical isolates of T.
      callipaeda expressed high genetic diversity. Based on the cox1 gene, a total of
      21 haplotypes were identified. One only circulated in European countries (Hap1),
      while the other 20 haplotypes were dispersed in Korea, Japan and China. There
      were five nucleotide positions in the cox1 sequences that were confirmed as
      invariable among individuals from Europe and Asia, but the sequences were
      distinct between these two regions. Population differences between Europe and
      Asian countries were greater than those among China, Korea and Japan. The T.
      callipaeda populations from Europe and Asia should be divided into two separate
      sub-populations. These two groups started to diverge during the middle
      Pleistocene. Neutrality tests, mismatch distribution and Bayesian skyline plot
      (BSP) analysis all rejected possible population expansion of T. callipaeda.
      CONCLUSIONS: The Asian population of T. callipaeda has a high level of genetic
      diversity, but further studies should be performed to explore the biology,
      ecology and epidemiology of T. callipaeda.

PMID- 29324739
TI  - Mansonella perstans microfilaremic individuals are characterized by enhanced type
      2 helper T and regulatory T and B cell subsets and dampened systemic innate and
      adaptive immune responses.
AB  - The filarial nematode Mansonella perstans is endemic throughout Africa, northern
      South America and the Caribbean. Interestingly, M. perstans-infected individuals
      present no distinct clinical picture associated with certain pathology. Due to
      its relatively silent nature, research on this tropical disease has been
      neglected, especially M. perstans-driven immune responses. A hindrance in
      obtaining data on M. perstans-specific responses has been the inability to obtain
      adult worms since their habitats in serous cavities are difficult to access.
      Thus, in this study, for the first time, we used Mansonella perstans worm antigen
      extract as stimulant to obtain filarial-specific recall and immunoglobulin
      responses from M. perstans microfilaremic individuals (Mp MF+) from Cameroon.
      Moreover, systemic immune profiles in sera and immune cell composition in
      peripheral blood from Mp MF+ and amicrofilaremic individuals (Mp MF-) were
      obtained. Our data reveal that Mp MF+ individuals showed significantly reduced
      cytokine (IL-4, IL-6 and IL-12p70) and chemokine levels (IL-8 and RANTES), but
      significantly higher MIP-1beta as well as increased M. perstans-specific IgG4
      levels compared to Mp MF- individuals. In contrast, upon re-stimulation with worm
      antigen extract, IFN-gamma, IL-13, IL-10 and IL-17A secretion was enhanced in
      cell cultures from Mp MF+ individuals when compared to those from cultures of
      healthy European individuals. Moreover, analysis of immune cell composition in
      peripheral blood from Mp MF+ individuals revealed increased type 2 helper T
      (Th2), natural killer (NK), regulatory B and T cell (Breg and Treg) subsets but
      decreased type 1 regulatory T (Tr1) cells. In summary, this study deciphers for
      the first time, M. perstans-specific immune responses using worm antigen extract
      and shows that patent M. perstans infections have distinct Th2, Breg and Treg
      subsets accompanied with reduced systemic innate and adaptive immune responses
      and dominant filarial-specific IgG4 levels.

PMID- 29324740
TI  - Dietary intake and diabetic retinopathy: A systematic review.
AB  - INTRODUCTION: The evidence linking dietary intake with diabetic retinopathy (DR)
      is growing but unclear. We conducted a systematic review of the association
      between dietary intake and DR. METHODS: We systematically searched PubMed,
      Embase, Medline, and the Cochrane Central register of controlled trials, for
      publications between January 1967 and January 2017 using standardized criteria
      for diet and DR. Interventional and observational studies investigating micro-
      and macro-nutrient intakes; food and beverage consumptions; and dietary patterns
      were included. Study quality was evaluated using a modified Newcastle-Ottawa
      scale for observational studies, and the Cochrane collaboration tool for
      interventional studies. RESULTS: Of 4265 titles initially identified, 31 studies
      (3 interventional, 28 Observational) were retained. Higher intakes of dietary
      fibre, oily fish, and greater adherence to a Mediterranean diet were protective
      of DR. Conversely, high total caloric intake was associated with higher risk of
      DR. No significant associations of carbohydrate, vitamin D, and sodium intake
      with DR were found. Associations of antioxidants, fatty acids, proteins and
      alcohol with DR remain equivocal. CONCLUSIONS: Dietary fibre, oily fish, a
      Mediterranean diet and a reduced caloric intake are associated with lower risk of
      DR. Longitudinal data and interventional models are warranted to confirm our
      findings and better inform clinical guidelines.

PMID- 29324741
TI  - Facilitating healthcare decisions by assessing the certainty in the evidence from
      preclinical animal studies.
AB  - Laboratory animal studies are used in a wide range of human health related
      research areas, such as basic biomedical research, drug research, experimental
      surgery and environmental health. The results of these studies can be used to
      inform decisions regarding clinical research in humans, for example the decision
      to proceed to clinical trials. If the research question relates to potential
      harms with no expectation of benefit (e.g., toxicology), studies in experimental
      animals may provide the only relevant or controlled data and directly inform
      clinical management decisions. Systematic reviews and meta-analyses are important
      tools to provide robust and informative evidence summaries of these animal
      studies. Rating how certain we are about the evidence could provide important
      information about the translational probability of findings in experimental
      animal studies to clinical practice and probably improve it. Evidence summaries
      and certainty in the evidence ratings could also be used (1) to support selection
      of interventions with best therapeutic potential to be tested in clinical trials,
      (2) to justify a regulatory decision limiting human exposure (to drug or toxin),
      or to (3) support decisions on the utility of further animal experiments. The
      Grading of Recommendations, Assessment, Development, and Evaluation (GRADE)
      approach is the most widely used framework to rate the certainty in the evidence
      and strength of health care recommendations. Here we present how the GRADE
      approach could be used to rate the certainty in the evidence of preclinical
      animal studies in the context of therapeutic interventions. We also discuss the
      methodological challenges that we identified, and for which further work is
      needed. Examples are defining the importance of consistency within and across
      animal species and using GRADE's indirectness domain as a tool to predict
      translation from animal models to humans.

PMID- 29324743
TI  - An enhanced artificial bee colony algorithm (EABC) for solving dispatching of
      hydro-thermal system (DHTS) problem.
AB  - The dispatching of hydro-thermal system is a nonlinear programming problem with
      multiple constraints and high dimensions and the solution techniques of the model
      have been a hotspot in research. Based on the advantage of that the artificial
      bee colony algorithm (ABC) can efficiently solve the high-dimensional problem, an
      improved artificial bee colony algorithm has been proposed to solve DHTS problem
      in this paper. The improvements of the proposed algorithm include two aspects. On
      one hand, local search can be guided in efficiency by the information of the
      global optimal solution and its gradient in each generation. The global optimal
      solution improves the search efficiency of the algorithm but loses diversity,
      while the gradient can weaken the loss of diversity caused by the global optimal
      solution. On the other hand, inspired by genetic algorithm, the nectar resource
      which has not been updated in limit generation is transformed to a new one by
      using selection, crossover and mutation, which can ensure individual diversity
      and make full use of prior information for improving the global search ability of
      the algorithm. The two improvements of ABC algorithm are proved to be effective
      via a classical numeral example at last. Among which the genetic operator for the
      promotion of the ABC algorithm's performance is significant. The results are also
      compared with those of other state-of-the-art algorithms, the enhanced ABC
      algorithm has general advantages in minimum cost, average cost and maximum cost
      which shows its usability and effectiveness. The achievements in this paper
      provide a new method for solving the DHTS problems, and also offer a novel
      reference for the improvement of mechanism and the application of algorithms.

PMID- 29324742
TI  - Functional characterization of adaptive variation within a cis-regulatory element
      influencing Drosophila melanogaster growth.
AB  - Gene expression variation is a major contributor to phenotypic diversity within
      species and is thought to play an important role in adaptation. However, examples
      of adaptive regulatory polymorphism are rare, especially those that have been
      characterized at both the molecular genetic level and the organismal level. In
      this study, we perform a functional analysis of the Drosophila melanogaster
      CG9509 enhancer, a cis-regulatory element that shows evidence of adaptive
      evolution in populations outside the species' ancestral range in sub-Saharan
      Africa. Using site-directed mutagenesis and transgenic reporter gene assays, we
      determined that 3 single nucleotide polymorphisms are responsible for the
      difference in CG9509 expression that is observed between sub-Saharan African and
      cosmopolitan populations. Interestingly, while 2 of these variants appear to have
      been the targets of a selective sweep outside of sub-Saharan Africa, the variant
      with the largest effect on expression remains polymorphic in cosmopolitan
      populations, suggesting it may be subject to a different mode of selection. To
      elucidate the function of CG9509, we performed a series of functional and
      tolerance assays on flies in which CG9509 expression was disrupted. We found that
      CG9509 plays a role in larval growth and influences adult body and wing size, as
      well as wing loading. Furthermore, variation in several of these traits was
      associated with variation within the CG9509 enhancer. The effect on growth
      appears to result from a modulation of active ecdysone levels and expression of
      growth factors. Taken together, our findings suggest that selection acted on 3
      sites within the CG9509 enhancer to increase CG9509 expression and, as a result,
      reduce wing loading as D. melanogaster expanded out of sub-Saharan Africa.

PMID- 29324744
TI  - QCloud: A cloud-based quality control system for mass spectrometry-based
      proteomics laboratories.
AB  - The increasing number of biomedical and translational applications in mass
      spectrometry-based proteomics poses new analytical challenges and raises the need
      for automated quality control systems. Despite previous efforts to set standard
      file formats, data processing workflows and key evaluation parameters for quality
      control, automated quality control systems are not yet widespread among
      proteomics laboratories, which limits the acquisition of high-quality results,
      inter-laboratory comparisons and the assessment of variability of instrumental
      platforms. Here we present QCloud, a cloud-based system to support proteomics
      laboratories in daily quality assessment using a user-friendly interface, easy
      setup, automated data processing and archiving, and unbiased instrument
      evaluation. QCloud supports the most common targeted and untargeted proteomics
      workflows, it accepts data formats from different vendors and it enables the
      annotation of acquired data and reporting incidences. A complete version of the
      QCloud system has successfully been developed and it is now open to the
      proteomics community (http://qcloud.crg.eu). QCloud system is an open source
      project, publicly available under a Creative Commons License Attribution
      ShareAlike 4.0.

PMID- 29324745
TI  - Proof-of-concept study of an at-home, engaging, digital intervention for
      pediatric ADHD.
AB  - OBJECTIVE: Pharmacological and behavioral therapies have limited impact on the
      distinct neurocognitive impairments associated with ADHD, and existing cognitive
      training programs have shown limited efficacy. This proof-of-concept study
      assessed treatment acceptability and explored outcomes for a novel digital
      treatment targeting cognitive processes implicated in ADHD. METHOD: Participants
      included 40 children with ADHD and 40 children without ADHD. Following
      psychiatric screening, ADHD ratings, and baseline neuropsychological measures,
      participants completed 28-days of at-home treatment. Neuropsychological
      assessment was repeated at end-of-study along with treatment satisfaction
      measures. RESULTS: Eighty-four percent of treatment sessions were completed and
      ratings showed strong intervention appeal. Significant improvements were observed
      on a computerized attention task for the ADHD group and a highly impaired ADHD
      High Severity subgroup. There was no change for the non-ADHD group. Spatial
      working memory also improved for the ADHD group and the ADHD High Severity
      subgroup. CONCLUSION: Findings provide preliminary support that this treatment
      may improve attention, working memory, and inhibition in children with ADHD.
      Future research requires larger-scale randomized controlled trials that also
      evaluate treatment impact on functional impairments. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT01943539.

PMID- 29324746
TI  - The relationship between observational scale and explained variance in benthic
      communities.
AB  - This study addresses the impact of spatial scale on explaining variance in
      benthic communities. In particular, the analysis estimated the fraction of
      community variation that occurred at a spatial scale smaller than the sampling
      interval (i.e., the geographic distance between samples). This estimate is
      important because it sets a limit on the amount of community variation that can
      be explained based on the spatial configuration of a study area and sampling
      design. Six benthic data sets were examined that consisted of faunal abundances,
      common environmental variables (water depth, grain size, and surficial percent
      cover), and sonar backscatter treated as a habitat proxy (categorical acoustic
      provinces). Redundancy analysis was coupled with spatial variograms generated by
      multiscale ordination to quantify the explained and residual variance at
      different spatial scales and within and between acoustic provinces. The amount of
      community variation below the sampling interval of the surveys (< 100 m) was
      estimated to be 36-59% of the total. Once adjusted for this small-scale
      variation, > 71% of the remaining variance was explained by the environmental and
      province variables. Furthermore, these variables effectively explained the
      spatial structure present in the infaunal community. Overall, no scale problems
      remained to compromise inferences, and unexplained infaunal community variation
      had no apparent spatial structure within the observational scale of the surveys
      (> 100 m), although small-scale gradients (< 100 m) below the observational scale
      may be present.

PMID- 29324747
TI  - Association of atrial fibrillation and cancer: Analysis from two large population
      based case-control studies.
AB  - BACKGROUND: An association between atrial fibrillation (AF) and risk of cancer
      has been suggested in several studies, including prospective cohort studies.
      However, the magnitude and the temporal nature of this association remain
      unclear. METHODS: Data from two large prospective population-based case-control
      studies, the Molecular Epidemiology of Colorectal Cancer (MECC, n = 8,383) and
      the Breast Cancer in Northern Israel Study (BCINIS, n = 11,608), were used to
      better understand the nature and temporality of a possible association between
      cancer diagnosis and AF events before and after cancer diagnosis. A case-control
      study approach was employed to study prior AF as a risk factor for cancer, and a
      cohort study approach was employed to study incident cancer as a risk factor for
      AF. RESULTS: AF was associated with a significant reduced odds of cancer as
      reflected in the case-control approach, with an adjusted OR = 0.77 (95% CI, 0.65
      0.91), while cancer was not found to be significantly associated with elevated
      risk of AF in the cohort approach, with an adjusted HR = 1.10 (0.98-1.23). The
      immediate period (90 days) after an AF event was associated with a 1.85 times
      increased risk of cancer, and the immediate period after the diagnosis of cancer
      was associated with a 3.4 fold increased risk of AF. These findings probably
      reflect both the effect of acute transient conditions associated with new cancer
      diagnosis and detection bias. Similar results were identified with colorectal and
      breast cancer cases. CONCLUSIONS: Atrial fibrillation of longer than 90 days
      duration is associated with reduced odds of new cancer diagnosis. The results of
      this study suggest that an association observed in prior research may be due to
      instances related to cancer diagnosis and detection bias rather than a causal
      relationship. However, there may be bias in the sampling and residual confounding
      that distort the associations.

PMID- 29324748
TI  - Trans10,cis12 conjugated linoleic acid inhibits proliferation and migration of
      ovarian cancer cells by inducing ER stress, autophagy, and modulation of Src.
AB  - The goal of this study was to investigate the anti-cancer effects of
      Trans10,cis12 conjugated linoleic acid (t10,c12 CLA). MTT assays and QCMTM
      chemotaxis 96-wells were used to test the effect of t10,c12 CLA on the
      proliferation and migration and invasion of cancer cells. qPCR and Western
      Blotting were used to determine the expression of specific factors. RNA
      sequencing was conducted using the Illumina platform and apoptosis was measured
      using a flow cytometry assay. t10,c12 CLA (IC50, 7 MUM) inhibited proliferation
      of ovarian cancer cell lines SKOV-3 and A2780. c9,t11 CLA did not attenuate the
      proliferation of these cells. Transcription of 165 genes was significantly
      repressed and 28 genes were elevated. Genes related to ER stress, ATF4, CHOP, and
      GADD34 were overexpressed whereas EDEM2 and Hsp90, genes required for proteasomal
      degradation of misfolded proteins, were downregulated upon treatment. While
      apoptosis was not detected, t10,c12 CLA treatment led to 9-fold increase in
      autophagolysosomes and higher levels of LC3-II. G1 cell cycle arrest in treated
      cells was correlated with phosphorylation of GSK3beta and loss of beta-catenin.
      microRNA miR184 and miR215 were upregulated. miR184 likely contributed to G1
      arrest by downregulating E2F1. miR215 upregulation was correlated with increased
      expression of p27/Kip-1. t10,c12 CLA-mediated inhibition of invasion and
      migration correlated with decreased expression of PTP1b and decreased Src
      activation by inhibiting phosphorylation at Tyr416. Due to its ability to inhibit
      proliferation and migration, t10,c12 CLA should be considered for treatment of
      ovarian cancer.

PMID- 29324749
TI  - Brand switching and toxic chemicals in cigarette smoke: A national study.
AB  - INTRODUCTION: US law requires disclosure of quantities of toxic chemicals
      (constituents) in cigarette smoke by brand and sub-brand. This information may
      drive smokers to switch to cigarettes with lower chemical quantities, under the
      misperception that doing so can reduce health risk. We sought to understand past
      brand-switching behavior and whether learning about specific chemicals in
      cigarette smoke increases susceptibility to brand switching. METHODS:
      Participants were US adult smokers surveyed by phone (n = 1,151, probability
      sample) and online (n = 1,561, convenience sample). Surveys assessed whether
      smokers had ever switched cigarette brands or styles to reduce health risk and
      about likelihood of switching if the smoker learned their brand had more of a
      specific chemical than other cigarettes. Chemicals presented were nicotine,
      carbon monoxide, lead, formaldehyde, arsenic, and ammonia. RESULTS: Past brand
      switching to reduce health risk was common among smokers (43% in phone survey,
      28% in online survey). Smokers who were female, over 25, and current "light"
      cigarette users were more likely to have switched brands to reduce health risks
      (all p < .05). Overall, 61-92% of smokers were susceptible to brand switching
      based on information about particular chemicals. In both samples, lead,
      formaldehyde, arsenic, and ammonia led to more susceptibility to switch than
      nicotine (all p < .05). CONCLUSIONS: Many US smokers have switched brands or
      styles to reduce health risks. The majority said they might or would definitely
      switch brands if they learned their cigarettes had more of a toxic chemical than
      other brands. Brand switching is a probable unintended consequence of
      communications that show differences in smoke chemicals between brands.

PMID- 29324750
TI  - Biochar derived from corn straw affected availability and distribution of soil
      nutrients and cotton yield.
AB  - Biochar application as a soil amendment has been proposed as a strategy to
      improve soil fertility and increase crop yields. However, the effects of
      successive biochar applications on cotton yields and nutrient distribution in
      soil are not well documented. A three-year field study was conducted to
      investigate the effects of successive biochar applications at different rates on
      cotton yield and on the soil nutrient distribution in the 0-100 cm soil profile.
      Biochar was applied at 0, 5, 10, and 20 t ha-1 (expressed as Control, BC5, BC10,
      and BC20, respectively) for each cotton season, with identical doses of chemical
      fertilizers. Biochar enhanced the cotton lint yield by 8.0-15.8%, 9.3-13.9%, and
      9.2-21.9% in 2013, 2014, and 2015, respectively, and high levels of biochar
      application achieved high cotton yields each year. Leaching of soil nitrate was
      reduced, while the pH values, soil organic carbon, total nitrogen (N), and
      available K content of the 0-20 cm soil layer were increased in 2014 and 2015.
      However, the changes in the soil available P content were less substantial. This
      study suggests that successive biochar amendments have the potential to enhance
      cotton productivity and soil fertility while reducing nitrate leaching.

PMID- 29324752
TI  - Tet protein function during Drosophila development.
AB  - The TET (Ten-eleven translocation) 1, 2 and 3 proteins have been shown to
      function as DNA hydroxymethylases in vertebrates and their requirements have been
      documented extensively. Recently, the Tet proteins have been shown to also
      hydroxylate 5-methylcytosine in RNA. 5-hydroxymethylcytosine (5hmrC) is enriched
      in messenger RNA but the function of this modification has yet to be elucidated.
      Because Cytosine methylation in DNA is barely detectable in Drosophila, it serves
      as an ideal model to study the biological function of 5hmrC. Here, we
      characterized the temporal and spatial expression and requirement of Tet
      throughout Drosophila development. We show that Tet is essential for viability as
      Tet complete loss-of-function animals die at the late pupal stage. Tet is highly
      expressed in neuronal tissues and at more moderate levels in somatic muscle
      precursors in embryos and larvae. Depletion of Tet in muscle precursors at early
      embryonic stages leads to defects in larval locomotion and late pupal lethality.
      Although Tet knock-down in neuronal tissue does not cause lethality, it is
      essential for neuronal function during development through its affects upon
      locomotion in larvae and the circadian rhythm of adult flies. Further, we report
      the function of Tet in ovarian morphogenesis. Together, our findings provide
      basic insights into the biological function of Tet in Drosophila, and may
      illuminate observed neuronal and muscle phenotypes observed in vertebrates.

PMID- 29324751
TI  - Stage-specific IFN-induced and IFN gene expression reveal convergence of type I
      and type II IFN and highlight their role in both acute and chronic stage of
      pathogenic SIV infection.
AB  - Interferons (IFNs) play a major role in controlling viral infections including
      HIV/SIV infections. Persistent up-regulation of interferon stimulated genes
      (ISGs) is associated with chronic immune activation and progression in SIV/HIV
      infections, but the respective contribution of different IFNs is unclear. We
      analyzed the expression of IFN genes and ISGs in tissues of SIV infected macaques
      to understand the respective roles of type I and type II IFNs. Both IFN types
      were induced in lymph nodes during early stage of primary infection and to some
      extent in rectal biopsies but not in PBMCs. Induction of Type II IFN expression
      persisted during the chronic phase, in contrast to undetectable induction of type
      I IFN expression. Global gene expression analysis with a major focus on ISGs
      revealed that at both acute and chronic infection phases most differentially
      expressed ISGs were inducible by both type I and type II IFNs and displayed the
      highest increases, indicating strong convergence and synergy between type I and
      type II IFNs. The analysis of functional signatures of ISG expression revealed
      temporal changes in IFN expression patterns identifying phase-specific ISGs.
      These results suggest that IFN-gamma strongly contribute to shape ISG
      upregulation in addition to type I IFN.

PMID- 29324753
TI  - MicroRNA signatures of endogenous Huntingtin CAG repeat expansion in mice.
AB  - In Huntington's disease (HD) patients and in model organisms, messenger RNA
      transcriptome has been extensively studied; in contrast, comparatively little is
      known about expression and potential role of microRNAs. Using RNA-sequencing, we
      have quantified microRNA expression in four brain regions and liver, at three
      different ages, from an allelic series of HD model mice with increasing CAG
      length in the endogenous Huntingtin gene. Our analyses reveal CAG length
      dependent microRNA expression changes in brain, with 159 microRNAs selectively
      altered in striatum, 102 in cerebellum, 51 in hippocampus, and 45 in cortex. In
      contrast, a progressive CAG length-dependent microRNA dysregulation was not
      observed in liver. We further identify microRNAs whose transcriptomic response to
      CAG length expansion differs significantly among the brain regions and validate
      our findings in data from a second, independent cohort of mice. Using existing
      mRNA expression data from the same animals, we assess the possible relationships
      between microRNA and mRNA expression and highlight candidate microRNAs that are
      negatively correlated with, and whose predicted targets are enriched in, CAG
      length dependent mRNA modules. Several of our top microRNAs (Mir212/Mir132,
      Mir218, Mir128 and others) have been previously associated with aspects of
      neuronal development and survival. This study provides an extensive resource for
      CAG length-dependent changes in microRNA expression in disease-vulnerable and 
      resistant brain regions in HD mice, and provides new insights for further
      investigation of microRNAs in HD pathogenesis and therapeutics.

PMID- 29324754
TI  - Fast, quantitative, murine cardiac 19F MRI/MRS of PFCE-labeled progenitor stem
      cells and macrophages at 9.4T.
AB  - PURPOSE: To a) achieve cardiac 19F-Magnetic Resonance Imaging (MRI) of perfluoro
      crown-ether (PFCE) labeled cardiac progenitor stem cells (CPCs) and bone-derived
      bone marrow macrophages, b) determine label concentration and cellular load
      limits, and c) achieve spectroscopic and image-based quantification. METHODS:
      Theoretical simulations and experimental comparisons of spoiled-gradient echo
      (SPGR), rapid acquisition with relaxation enhancement (RARE), and steady state at
      free precession (SSFP) pulse sequences, and phantom validations, were conducted
      using 19F MRI/Magnetic Resonance Spectroscopy (MRS) at 9.4 T. Successful cell
      labeling was confirmed using flow cytometry and confocal microscopy. For CPC and
      macrophage concentration quantification, in vitro and post-mortem cardiac
      validations were pursued with the use of the transfection agent FuGENE.
      Feasibility of fast imaging is demonstrated in murine cardiac acquisitions in
      vivo, and in post-mortem murine skeletal and cardiac applications. RESULTS:
      SPGR/SSFP proved favorable imaging sequences yielding good signal-to-noise ratio
      values. Confocal microscopy confirmed heterogeneity of cellular label uptake in
      CPCs. 19F MRI indicated lack of additional benefits upon label concentrations
      above 7.5-10 mg/ml/million cells. The minimum detectable CPC load was ~500k
      (~10k/voxel) in two-dimensional (2D) acquisitions (3-5 min) using the butterfly
      coil. Additionally, absolute 19F based concentration and intensity estimates
      (trifluoroacetic-acid solutions, macrophages, and labeled CPCs in vitro and post
      CPC injections in the post-mortem state) scaled linearly with fluorine
      concentrations. Fast, quantitative cardiac 19F-MRI was demonstrated with
      SPGR/SSFP and MRS acquisitions spanning 3-5 min, using a butterfly coil.
      CONCLUSION: The developed methodologies achieved in vivo cardiac 19F of
      exogenously injected labeled CPCs for the first time, accelerating imaging to a
      total acquisition of a few minutes, providing evidence for their potential for
      possible translational work.

PMID- 29324755
TI  - HIV-1 co-receptor tropism and liver fibrosis in HIV-infected patients.
AB  - BACKGROUND: In vitro, gp120 of both X4 and R5 HIV-1 strains activates human
      hepatic stellate cells, but if it can promote liver fibrosis in vivo is unknown.
      We aimed to evaluate if patients carrying X4 or R5 strains have a different liver
      fibrosis (LF) progression over time. METHODS: A total of 1,137 HIV-infected
      patients in ICONA cohort (21% females, 7% HCV co-infected) with an available
      determination of HIV-1 co-receptor tropism (CRT), a Fibrosis-4 Index for Liver
      Fibrosis (FIB-4) <3.25 and at least one-year follow-up were included. CRT was
      assessed by gp120 sequencing on plasma RNA and geno2pheno algorithm (10% false
      positive rate) or by Trofile. LF was assessed by means of FIB-4. LF progression
      was defined as an absolute score increase or a transition to higher fibrosis
      stratum and/or occurrence of liver-related clinical events. RESULTS: A total of
      249 (22%) patients carried X4 strains, which were associated with older age,
      lower CD4 count, lower nadir CD4, and intravenous drug use. Overall, X4 and R5
      patients had similar baseline FIB-4 scores and similar mean FIB-4 slope after a
      median follow-up of 35 months. There was no difference between X4 and R5 for time
      to LF progression (p = 0.925). Estimated risk of LF at 24 months (95% CI) after
      baseline in X4 and R5 was 10.6% (8.3-12.9) and 9.9% (5.9-14.0), respectively.
      Age, HCV co-infection, diabetes, HIV-duration, HIV-RNA>100.000 cp/mL,
      antiretroviral therapy exposure were associated with LF progression at
      multivariate analysis. CONCLUSIONS: A slight LF progression over time was
      observed in HIV-infected patients. No difference was demonstrated for X4 and R5
      HIV-1 strains in accelerating LF evolution.

PMID- 29324756
TI  - Associations of plasma clusterin and Alzheimer's disease-related MRI markers in
      adults at mid-life: The CARDIA Brain MRI sub-study.
AB  - BACKGROUND: Clinical and epidemiological studies of older persons have implicated
      clusterin in Alzheimer's disease (AD) pathogenesis. In the context of identifying
      early biomarkers of risk, we examined associations of plasma clusterin and
      characteristics of AD in middle-aged individuals from the community. MATERIALS
      AND METHODS: Subjects were 639 cognitively normal individuals (mean age 50 +/-
      3.5) from the Coronary Artery Risk Development in Young Adults (CARDIA) Brain MRI
      sub-study. Clusterin was quantified using ELISA (mean 255+/- 31 ng/ml).
      Associations were assessed between clusterin and volumes of brain regions known
      to atrophy in early AD, including entorhinal cortex (ECV), hippocampus (HV), and
      medial temporal lobe (MTLV) volumes (cm3). Total brain volume (TBV) and volumes
      of structures affected in later AD were examined for comparison. RESULTS: In
      multivariable models, higher clusterin had a negative non-linear association with
      ECV (combined left and right hemispheres), and this association was influenced by
      the highest clusterin levels. Compared to mean clusterin, 1 and 2 standard
      deviation (SD) level increases in clusterin were associated with -2.1% (95% CI: 
      3.3,-0.9) and -7.3% (95% CI: -11.3,-3.3) lower ECV, respectively. Similar
      relationships were observed between clusterin and HV, although the relationship
      was stronger for left-side HV than the right-side. However, the association was
      not significant after adjusting for covariates. Negative non-linear associations
      between clusterin and MTLV were strongest for the left side: compared to mean
      clusterin, 1 and 2 SD level increases in clusterin were associated with -0.9%
      (95% CI: -1.9, 0.1) and -3.7% (95% CI: -7.1, -0.3) lower MTLV. There were no
      significant associations between clusterin and brain structures affected in later
      AD. CONCLUSIONS: In middle-aged adults unselected for AD, plasma clusterin was
      associated with lower volume of the entorhinal cortex, an area that atrophies
      early in AD. Clusterin could be informative as part of a multi-component
      preclinical marker for AD.

PMID- 29324757
TI  - Genome downsizing, physiological novelty, and the global dominance of flowering
      plants.
AB  - The abrupt origin and rapid diversification of the flowering plants during the
      Cretaceous has long been considered an "abominable mystery." While the cause of
      their high diversity has been attributed largely to coevolution with pollinators
      and herbivores, their ability to outcompete the previously dominant ferns and
      gymnosperms has been the subject of many hypotheses. Common among these is that
      the angiosperms alone developed leaves with smaller, more numerous stomata and
      more highly branching venation networks that enable higher rates of
      transpiration, photosynthesis, and growth. Yet, how angiosperms pack their leaves
      with smaller, more abundant stomata and more veins is unknown but linked-we show
      to simple biophysical constraints on cell size. Only angiosperm lineages
      underwent rapid genome downsizing during the early Cretaceous period, which
      facilitated the reductions in cell size necessary to pack more veins and stomata
      into their leaves, effectively bringing actual primary productivity closer to its
      maximum potential. Thus, the angiosperms' heightened competitive abilities are
      due in no small part to genome downsizing.

PMID- 29324758
TI  - Settlement and post-settlement survival rates of the white seabream (Diplodus
      sargus) in the western Mediterranean Sea.
AB  - Survival during the settlement window is a limiting variable for recruitment. The
      survival is believed to be strongly determined by biological interactions and sea
      conditions, however it has been poorly investigated. We examined the settlement
      patterns related to relevant biotic and abiotic factors (i.e. Density-dependence,
      wind stress, wave height and coastal current velocity) potentially determining
      post-settler survival rates of a coastal necto-benthic fish of wide distribution
      in the Mediterranean and eastern Atlantic, the white seabream (Diplodus sargus).
      An observational study of the demography of juveniles of this species was carried
      out at six coves in Menorca Island (Balearic Islands, western Mediterranean).
      Three of the coves were located in the northern and wind exposed coast, at the
      Northeast (NE) side; while the other three were found along the southern and
      sheltered coast, at the Southwest (SW) side of the island. The settlement period
      extended from early May to late June and maximum juvenile densities at the
      sampling sites varied between 5 and 11 ind. m-1 with maximum values observed in
      late May simultaneously occurring in the two coasts. Our analysis of juvenile
      survival, based on the interpretation of the observed patters using an individual
      based model (IBM), revealed two stages in the size-mortality relationships. An
      initial density-dependent stage was observed for juveniles up to 20 mm TL,
      followed by a density independent stage when other factors dominated the survival
      at sizes > 20 mm TL. No significant environmental effects were observed for the
      small size class (<20mm TL). Different significant environmental effects
      affecting NE and SW coves were observed for the medium (20-30mm TL) and large
      (>30mm TL) size class. In the NE, the wind stress consistently affected the
      density of fish of 20-30 mm and >30 mm TL with a dome-shape effect with higher
      densities at intermediate values of wind stress and negative effect at the
      extremes. The best models applied in the SW coves showed a significant non-linear
      negative effect on fish density that was also consistent for both groups 20-30 mm
      and >30 mm TL. Higher densities were observed at low values of wave height in the
      two groups. Because of these variations, the number of juveniles present at the
      end of the period was unrelated to their initial density and average survival
      varied among locations. In consequence, recruitment was (1) primarily limited by
      denso-dependient procedures at settlement stage, and (2) by sea conditions at
      post-settlement, where extreme wave conditions depleted juveniles. Accordingly,
      regional hydrodynamic conditions during the settlement season produced
      significant impacts on the juvenile densities depending on their size and with
      contrasted effects in respectto cove orientation. The similar strength in larval
      supply between coves, in addition to the similar mean phenology for settlers in
      the north and south of the Island, suggests that all fish may come from the same
      parental reproductive pool. These factors should be taken into account when
      assessing relationships between settlers, recruits and adults of white seabream.

PMID- 29324759
TI  - Disease burden of methylmercury in the German birth cohort 2014.
AB  - This study aimed to estimate the disease burden of methylmercury for children
      born in Germany in the year 2014. Humans are mainly exposed to methylmercury when
      they eat fish or seafood. Prenatal methylmercury exposure is associated with IQ
      loss. To quantify this disease burden, we used Monte Carlo simulation to estimate
      the incidence of mild and severe mental retardation in children born to mothers
      who consume fish based on empirical data. Subsequently, we calculated the disease
      burden with the disability-adjusted life years (DALY)-method. DALYs combine
      mortality and morbidity in one measure and quantify the gap between an ideal
      situation, where the entire population experiences the standard life expectancy
      without disease and disability, and the actual situation. Thus, one DALY
      corresponds to the loss of one year of life in good health. The methylmercury
      induced burden of disease for the German birth cohort 2014 was an average of
      14,186 DALY (95% CI 12,915-15,440 DALY). A large majority of the DALYs was
      attributed to morbidity as compared to mortality. Of the total disease burden,
      98% were attributed to mild mental retardation, which only leads to morbidity.
      The remaining disease burden was a result of severe mental retardation with equal
      proportions of premature death and morbidity.

PMID- 29324761
TI  - Cross-linguistic regularities and learner biases reflect "core" mechanics.
AB  - Recent research in infant cognition and adult vision suggests that the mechanical
      object relationships may be more salient and naturally attention grabbing than
      similar but non-mechanical relationships. Here we examine two novel sources of
      evidence from language related to this hypothesis. In Experiments 1 and 2, we
      show that adults preferentially infer that the meaning of a novel preposition
      refers to a mechanical as opposed to a non-mechanical relationship. Experiments 3
      and 4 examine cross-linguistic adpositions obtained on a large scale from
      machines or from experts, respectively. While these methods differ in the ease of
      data collection relative to the reliability of the data, their results converge:
      we find that across a range of diverse and historically unrelated languages,
      adpositions (such as prepositions) referring to the mechanical relationships of
      containment (e.g "in") and support (e.g. "on") are systematically shorter than
      closely matched but not mechanical words such as "behind," "beside," "above,"
      "over," "out," and "off." These results first suggest that languages regularly
      contain traces of core knowledge representations and that cross-linguistic
      regularities can therefore be a useful and easily accessible form of information
      that bears on the foundations of non-linguistic thought.

PMID- 29324760
TI  - Bionomics of Phlebotomus argentipes in villages in Bihar, India with insights
      into efficacy of IRS-based control measures.
AB  - BACKGROUND: Visceral leishmaniasis (VL) is a deadly vector-borne disease.
      Approximately 90% of Indian VL cases occur in Bihar, where the sand fly,
      Phlebotomus argentipes, is the principal vector. Sand fly control in Bihar
      consists of indoor residual spraying (IRS), the practice of spraying the inner
      walls of village dwellings with insecticides. Prior researchers have evaluated
      success of IRS-control by estimating vector abundance in village houses, but the
      number of sampling periods (n = 2-3) were minimal, and outdoor-resting P.
      argentipes were neglected. We describe a large-scale field study, performed in 24
      villages within two Bihari districts, during which P. argentipes were collected
      biweekly over 47-weeks, in cattle enclosures, houses, and outdoors in peri
      domestic vegetation. The objectives of this study were to provide updated P.
      argentipes ecological field data, and determine if program-initiated IRS
      treatment had led to noticeable differences in vector abundance. PRINCIPAL
      FINDINGS: P. argentipes (n = 126,901) relative abundance was greatest during the
      summer months (June-August) when minimum temperatures were highest. P. argentipes
      were most frequently collected from cattle enclosures (~46% total; ~56% blood
      fed). Many sand flies were found to have taken blood from multiple sources, with
      ~81% having blood fed on humans and ~60% blood feeding on bovines. Nonparametric
      statistical tests were determined most appropriate for evaluating IRS-treatment.
      Differences in P. argentipes abundance in houses, cattle enclosures and
      vegetation were detected between IRS-treated and untreated villages in only ~9%
      of evaluation periods occurring during the peak period of human-vector exposure
      (June-August) and in ~8% of the total observations. No significant differences
      were detected between the numbers of P. argentipes collected in vegetation close
      to the experimental villages. CONCLUSION: The results of this study provide
      updated data regarding P. argentipes seasonal abundance, spatial distribution,
      and host preferances, and suggest vector abundance has not significantly declined
      in IRS-treated villages. We suggest that IRS be supplemented with vector control
      strategies targeting exophagic, exophilic P. argentipes, and that disease
      surveillance be accompanied by rigorous vector population monitoring.

PMID- 29324763
TI  - Factors associated with urinary tract infections among HIV-1 infected patients.
AB  - BACKGROUND: Urinary tract infections remain an important yet underinvestigated
      clinical problem among HIV infected patients. Here we analyze factors associated
      with its occurrence and the spectrum of bacterial pathogens identified in the
      group of patients followed at the HIV Out-Patient Clinic in Warsaw. METHODS:
      Clinic database collected all medical information on patients routinely followed
      since 1994 to 2015. All patients with available urine culture were included into
      analyses, only the first culture was included. In statistical analyses logistic
      regression models were used to identify factors associated with positive culture.
      RESULTS: In total 608 patients had urine culture performed, 176 (28.9%) were
      females and 432 (71,1%) were males, 378 (62.2%) registered in care before/in
      2007, 258 (42.4%) infected through homosexual contact. Median baseline lymphocyte
      CD4+ count was 385 (IQR:204-565) cells/MUl and median nadir lymphocyte CD4+ count
      197 (86-306) cells/MUl. One hundred and eighteen patients were actively infected
      with HCV, as defined by positive real-time PCR. In total 141 (23.2%) patients had
      positive urine culture, the most common bacterial pathogen was E.coli (58.2%) and
      E. faecalis (12.8%). Patients with urinary tract infection were more likely to be
      female (51.8% vs. 22.1%, p<0.0001), infected through other than homosexual mode
      (80.1% vs. 50.7%, p<0.0001), with lower nadir CD4 count (139 vs. 221 cells/MUl,
      p<0.0001) and lower baseline HIV RNA (4.02 vs. 4.35 log copies/ml, p = 0.01) and
      less likely to be HCV RNA positive (26.9% vs. 49.2%, p = 0.01). In multivariate
      regression model being registered before/in 2007 (OR = 2.10; [95%CI: 1.24-3.56]),
      infected through other than homosexual mode (2.05;[1.18-3.56]) and female gender
      (2.14;[1.33-3.44]) were increasing and higher nadir CD4+ count decreasing
      (0.92;[0.85-0.99]) the odds of urinary tract infection. CONCLUSIONS: We have
      identified that almost one third of patients had urinary tract infections with
      non-typical bacterial pathogens. Population with increased odds of urinary tract
      infections are women, patients infected through other than homosexual contacts
      and those registered before 2007.

PMID- 29324764
TI  - Competing for the same value segments? Insight into the volatile Dutch political
      landscape.
AB  - Values are central to public debates today. Human values convey broad goals that
      serve as guiding principles in a person's life and value priorities differ across
      people in society. Groups in society holding opposing values (e.g., universalism
      versus security) will make different choices when voting in an election. Whereas
      over time, values are relatively stable, the number and type of political parties
      as well as the political values they communicate and disseminate have been
      changing. Groups of people holding the same human values may therefore vote for
      another (new) party in a later election. We focus on analyzing the relationship
      between human values and voting in elections, introducing a new methodology to
      analyze how value profiles relate to political support over time. We investigate
      the Dutch multi-party political system over five waves of the European Social
      Survey, spanning 2002 until 2010. Whilst previous research has focused on
      individual values separately and focused on voters only, we (1) distinguish
      groups holding a similar set of opposing and compatible values (value profile)
      instead of focusing on single values in the the entire population; (2)
      incorporate a correction for differences in scale use in our model; (3) compare
      voting over time; (4) include non-voters, a growing group in Dutch society. We
      find evidence that specific value profiles are related to voting for a specific
      set of political parties. We also find that specific value profiles distinguish
      non-voters from voters and that voters for populist parties resemble non-voters.

PMID- 29324762
TI  - Obesogenic diets alter metabolism in mice.
AB  - Obesity and accompanying metabolic disease is negatively correlated with lung
      health yet the exact mechanisms by which obesity affects the lung are not well
      characterized. Since obesity is associated with lung diseases as chronic
      bronchitis and asthma, we designed a series of experiments to measure changes in
      lung metabolism in mice fed obesogenic diets. Mice were fed either control or
      high fat/sugar diet (45%kcal fat/17%kcal sucrose), or very high fat diet (60%kcal
      fat/7% sucrose) for 150 days. We performed untargeted metabolomics by GC-TOFMS
      and HILIC-QTOFMS and lipidomics by RPLC-QTOFMS to reveal global changes in lung
      metabolism resulting from obesity and diet composition. From a total of 447
      detected metabolites, we found 91 metabolite and lipid species significantly
      altered in mouse lung tissues upon dietary treatments. Significantly altered
      metabolites included complex lipids, free fatty acids, energy metabolites, amino
      acids and adenosine and NAD pathway members. While some metabolites were altered
      in both obese groups compared to control, others were different between
      obesogenic diet groups. Furthermore, a comparison of changes between lung, kidney
      and liver tissues indicated few metabolic changes were shared across organs,
      suggesting the lung is an independent metabolic organ. These results indicate
      obesity and diet composition have direct mechanistic effects on composition of
      the lung metabolome, which may contribute to disease progression by lung-specific
      pathways.

PMID- 29324766
TI  - Liver transplantation for alcoholic hepatitis: A systematic review with meta
      analysis.
AB  - BACKGROUND: The rate of alcohol relapse among patients who underwent liver
      transplantation for alcoholic hepatitis (AH) is not precisely known. AIM:
      Synthesize the available evidence on liver transplantation for AH to assess
      alcohol relapse and 6-month survival. METHODS: Meta-analysis of trials evaluating
      liver transplantation for AH, either clinically severe or diagnosed on the
      explant. RESULTS: Eleven studies were included. The pooled estimate rate for
      alcohol relapse was 0.22 (95% CI = 0.12-0.36) in overall analysis with high
      heterogeneity between studies (I2 = 76%), 0.20 (95% CI = 0.07-0.43) in the
      subgroup analysis including patients with clinically severe AH (I2 = 84%), 0.14
      (95% CI = 0.08-0.23) among patients with clinically severe AH in sensitivity
      analysis excluding the discrepant studies that did not use stringent selection
      criteria for liver transplantation (I2 = 0%), and 0.15 (95% CI = 0.07-0.27) for
      recurrent harmful alcohol consumption among patients with clinically severe AH
      (I2 = 3%). The risk of alcohol relapse was not different between AH transplanted
      patients and patients with alcoholic cirrhosis who underwent elective liver
      transplantation in sensitivity analysis excluding the discrepant studies (OR =
      1.68, 95%CI = 0.79-3.58, p = 0.2, I2 = 16%). The pooled estimate rate for 6-month
      survival was 0.85 (95% CI = 0.77-0.91, I2 = 49%), and 0.80 among patients
      transplanted for clinically severe AH (95% CI = 0.69-0.88, I2 = 30%). AH
      transplanted patients had similar 6-month survival to patients with alcoholic
      cirrhosis who underwent elective liver transplantation (OR = 2.00, 95% CI = 0.95
      4.23, p = 0.07, I2 = 0%). CONCLUSION: Using stringent selection criteria, 14% of
      patients with clinically severe AH have alcohol relapse after liver
      transplantation. The percentage of alcohol relapse of AH transplanted patients is
      similar than that of patients who underwent elective liver transplantation.

PMID- 29324765
TI  - Brassinosteroids regulate root growth by controlling reactive oxygen species
      homeostasis and dual effect on ethylene synthesis in Arabidopsis.
AB  - The brassinosteroids (BRs) represent a class of phytohormones, which regulate
      numerous aspects of growth and development. Here, a det2-9 mutant defective in BR
      synthesis was identified from an EMS mutant screening for defects in root length,
      and was used to investigate the role of BR in root development in Arabidopsis.
      The det2-9 mutant displays a short-root phenotype, which is result from the
      reduced cell number in root meristem and decreased cell size in root maturation
      zone. Ethylene synthesis is highly increased in the det2-9 mutant compared with
      the wild type, resulting in the hyper-accumulation of ethylene and the consequent
      inhibition of root growth. The short-root phenotype of det2-9 was partially
      recovered in the det2-9/acs9 double mutant and det2-9/ein3/eil1-1 triple mutant
      which have defects either in ethylene synthesis or ethylene signaling,
      respectively. Exogenous application of BR showed that BRs either positively or
      negatively regulate ethylene biosynthesis in a concentration-dependent manner.
      Different from the BR induced ethylene biosynthesis through stabilizing ACSs
      stability, we found that the BR signaling transcription factors BES1 and BZR1
      directly interacted with the promoters of ACS7, ACS9 and ACS11 to repress their
      expression, indicating a native regulation mechanism under physiological levels
      of BR. In addition, the det2-9 mutant displayed over accumulated superoxide
      anions (O2-) compared with the wild-type control, and the increased O2- level was
      shown to contribute to the inhibition of root growth. The BR-modulated control
      over the accumulation of O2- acted via the peroxidase pathway rather than via the
      NADPH oxidase pathway. This study reveals an important mechanism by which the
      hormone cross-regulation between BRs and ethylene or/and ROS is involved in
      controlling root growth and development in Arabidopsis.

PMID- 29324767
TI  - Glass promotes the differentiation of neuronal and non-neuronal cell types in the
      Drosophila eye.
AB  - Transcriptional regulators can specify different cell types from a pool of
      equivalent progenitors by activating distinct developmental programs. The Glass
      transcription factor is expressed in all progenitors in the developing Drosophila
      eye, and is maintained in both neuronal and non-neuronal cell types. Glass is
      required for neuronal progenitors to differentiate as photoreceptors, but its
      role in non-neuronal cone and pigment cells is unknown. To determine whether
      Glass activity is limited to neuronal lineages, we compared the effects of
      misexpressing it in neuroblasts of the larval brain and in epithelial cells of
      the wing disc. Glass activated overlapping but distinct sets of genes in these
      neuronal and non-neuronal contexts, including markers of photoreceptors, cone
      cells and pigment cells. Coexpression of other transcription factors such as
      Pax2, Eyes absent, Lozenge and Escargot enabled Glass to induce additional genes
      characteristic of the non-neuronal cell types. Cell type-specific glass mutations
      generated in cone or pigment cells using somatic CRISPR revealed autonomous
      developmental defects, and expressing Glass specifically in these cells partially
      rescued glass mutant phenotypes. These results indicate that Glass is a
      determinant of organ identity that acts in both neuronal and non-neuronal cells
      to promote their differentiation into functional components of the eye.

PMID- 29324768
TI  - Identifying human diamine sensors for death related putrescine and cadaverine
      molecules.
AB  - Pungent chemical compounds originating from decaying tissue are strong drivers of
      animal behavior. Two of the best-characterized death smell components are
      putrescine (PUT) and cadaverine (CAD), foul-smelling molecules produced by
      decarboxylation of amino acids during decomposition. These volatile polyamines
      act as 'necromones', triggering avoidance or attractive responses, which are
      fundamental for the survival of a wide range of species. The few studies that
      have attempted to identify the cognate receptors for these molecules have
      suggested the involvement of the seven-helix trace amine-associated receptors
      (TAARs), localized in the olfactory epithelium. However, very little is known
      about the precise chemosensory receptors that sense these compounds in the
      majority of organisms and the molecular basis of their interactions. In this
      work, we have used computational strategies to characterize the binding between
      PUT and CAD with the TAAR6 and TAAR8 human receptors. Sequence analysis, homology
      modeling, docking and molecular dynamics studies suggest a tandem of negatively
      charged aspartates in the binding pocket of these receptors which are likely to
      be involved in the recognition of these small biogenic diamines.

PMID- 29324769
TI  - Impaired resolution of DSS-induced colitis in mice lacking the glucocorticoid
      receptor in myeloid cells.
AB  - Inflammatory bowel disease (IBD) is a highly prevalent intestinal disorder for
      which no cure exists. Currently, the standard first-line treatment of IBD
      consists of systemic glucocorticoid (GC) application, even though therapy can be
      complicated by unresponsiveness or adverse effects. In view of the importance of
      macrophages and neutrophils for the pathogenesis of IBD we set out to define the
      relevance of these cell types as targets of GC using the mouse model of DSS
      induced colitis. We found that the disease did not resolve in GRlysM mice lacking
      the GC receptor (GR) in myeloid cells after removal of the chemical insult. While
      clinical symptoms and tissue damage in the colon ameliorated again in GRflox
      mice, the disease further aggravated in GRlysM littermates. The observed
      difference coincided with an increased abundance of macrophages in inflammatory
      infiltrates in the colon of mutant mice whereas neutrophil and T cell numbers
      were similar. Concomitantly, systemic IL-6 secretion and mRNA levels of pro
      inflammatory cytokines in the colon were elevated in GRlysM mice and gene
      expression of scavenger receptors and IL-10 was diminished. Taken together, our
      results reveal an important role of myeloid cells as targets of GC in DSS-induced
      colitis and probably in IBD in humans as well.

PMID- 29324770
TI  - Phosphorus application reduces aluminum toxicity in two Eucalyptus clones by
      increasing its accumulation in roots and decreasing its content in leaves.
AB  - Under acidic conditions, aluminum (Al) toxicity is an important factor limiting
      plant productivity; however, the application of phosphorus (P) might alleviate
      the toxic effects of Al. In this study, seedlings of two vegetatively propagated
      Eucalyptus clones, E. grandis * E. urophylla 'G9' and E. grandis * E. urophylla
      'DH32-29'were subjected to six treatments (two levels of Al stress and three
      levels of P). Under excessive Al stress, root Al content was higher, whereas
      shoot and leaf Al contents were lower with P application than those without P
      application. Further, Al accumulation was higher in the roots, but lower in the
      shoots and leaves of G9 than in those of DH32-29. The secretion of organic acids
      was higher under Al stress than under no Al stress. Further, under Al stress, the
      roots of G9 secreted more organic acids than those of DH32-29. With an increase
      in P supply, Al-induced secretion of organic acids from roots decreased. Under Al
      stress, some enzymes, including PEPC, CS, and IDH, played important roles in
      organic acid biosynthesis and degradation. Thus, our results indicate that P can
      reduce Al toxicity via the fixation of elemental Al in roots and restriction of
      its transport to stems and leaves, although P application cannot promote the
      secretion of organic acid anions. Further, the higher Al-resistance of G9 might
      be attributed to the higher Al accumulation in and organic acid anion secretion
      from roots and the lower levels of Al in leaves.

PMID- 29324771
TI  - Impact of grouping complications on mortality in traumatic brain injury: A
      nationwide population-based study.
AB  - Traumatic brain injury (TBI) is an important health issue with high mortality.
      Various complications of physiological and cognitive impairment may result in
      disability or death after TBI. Grouping of these complications could be treated
      as integrated post-TBI syndromes. To improve risk estimation, grouping TBI
      complications should be investigated, to better predict TBI mortality. This study
      aimed to estimate mortality risk based on grouping of complications among TBI
      patients. Taiwan's National Health Insurance Research Database was used in this
      study. TBI was defined according to the International Classification of Diseases,
      Ninth Revision, Clinical Modification codes: 801-804 and 850-854. The association
      rule data mining method was used to analyze coexisting complications after TBI.
      The mortality risk of post-TBI complication sets with the potential risk factors
      was estimated using Cox regression. A total 139,254 TBI patients were enrolled in
      this study. Intracerebral hemorrhage was the most common complication among TBI
      patients. After frequent item set mining, the most common post-TBI grouping of
      complications comprised pneumonia caused by acute respiratory failure (ARF) and
      urinary tract infection, with mortality risk 1.55 (95% C.I.: 1.51-1.60), compared
      with those without the selected combinations. TBI patients with the combined
      combinations have high mortality risk, especially those aged <20 years with
      septicemia, pneumonia, and ARF (HR: 4.95, 95% C.I.: 3.55-6.88). We used post-TBI
      complication sets to estimate mortality risk among TBI patients. According to the
      combinations determined by mining, especially the combination of septicemia with
      pneumonia and ARF, TBI patients have a 1.73-fold increased mortality risk, after
      controlling for potential demographic and clinical confounders. TBI patients
      aged<20 years with each combination of complications also have increased
      mortality risk. These results could provide physicians and caregivers with
      important information to increase their awareness about sequences of clinical
      syndromes among TBI patients, to prevent possible deaths among these patients.

PMID- 29324772
TI  - Examination of Clock and Adcyap1 gene variation in a neotropical migratory
      passerine.
AB  - Complex behavioral traits, such as those making up a migratory phenotype, are
      regulated by multiple environmental factors and multiple genes. We investigated
      possible relationships between microsatellite variation at two candidate genes
      implicated in the control of migratory behavior, Clock and Adcyap1, and several
      aspects of migratory life-history and evolutionary divergence in the Painted
      Bunting (Passerina ciris), a species that shows wide variation in migratory and
      molting strategies across a disjunct distribution. We focused on Clock and
      Adcyap1 microsatellite variation across three Painted Bunting populations in
      Oklahoma, Louisiana, and North Carolina, and for the Oklahoma breeding population
      we used published migration tracking data on adult males to explore phenotypic
      variation in individual migratory behavior. We found no correlation between
      microsatellite allele size within either Clock and Adcyap1 relative to the
      initiation or duration of fall migration in adult males breeding in Oklahoma. We
      also show the lack of significant correlations with aspects of the migratory
      phenotype for the Louisiana population. Our research highlights the limitations
      of studying microsatellite allelic mutations that are of undetermined functional
      influence relative to complex behavioral phenotypes.

PMID- 29324773
TI  - The impact of a short-term cohousing initiative among schizophrenia patients,
      high school students, and their social context: A qualitative case study.
AB  - BACKGROUND: A number of programs have been developed to promote the contact
      between adolescents and mentally-ill patients, in order to break the stigma,
      improve understanding, promote mental health and prevent substance abuse. The aim
      of this study was to describe the experience of patients with schizophrenia, high
      school students, and their social context, participating in a short-term
      cohousing initiative. METHODS: A qualitative case-study approach was implemented.
      Patients with schizophrenia from the San Juan de Dios Psychiatric Hospital,
      female students from Almen High School, and participants from their social
      context (parents, hospital staff, and teachers) were included, using purposeful
      sampling. Data were collected from 51 participants (15 patients, nine students,
      11 hospital staff, six teachers, 10 parents) via non-participant observation,
      focus groups, informal interviews, researchers' field notes and patients'
      personal diaries and letters. A thematic analysis was performed. RESULTS: The
      themes identified included a) learning to live together: students and patients
      participate and learn together; b) the perception of the illness and the mentally
      ill: the barrier between health and disease is very slim, and society tends to
      avoid contact with those who are ill; c) change: a transformation takes place in
      students, in their self-perception, based on the real and intense nature of the
      experience; d) a trial and an opportunity: patients test their ability to live
      outside the hospital; e) discharge and readmission: discharge is experienced as
      both a liberation and a difficulty, whereas relapse and readmission are
      experienced as failures. CONCLUSIONS: Our findings can help us to better
      understand schizophrenia and encourage a more positive approach towards both the
      illness and those who suffer from it. These results may be used for the
      development of cohousing programs in controlled environments.

PMID- 29324774
TI  - Activated carbon N-acetylcysteine microcapsule protects against nonalcoholic
      fatty liver disease in young rats via activating telomerase and inhibiting
      apoptosis.
AB  - Non-alcoholic fatty liver disease (NAFLD) is becoming one of the world's most
      common chronic liver diseases in childhood, yet no therapy is available that has
      been approved by the food and drug administration (FDA). Previous studies have
      reported that telomere and telomerase are involved the development and
      progression of NAFLD. This study was designed to investigate the potential
      beneficial effects of activated carbon N-acetylcysteine (ACNAC) microcapsules on
      the development of NAFLD in young rats as well as the underlying mechanism(s)
      involved. Three-week old male Sprague Dawley rats were given high-fat diet (HFD)
      with/without ACNAC treatment for 7 consecutive weeks. Liver pathologies were
      determined by hematoxylin and eosin (H&E) and Oil Red O staining, as well as by
      changes in biochemical parameters of plasma alanine transaminase (ALT) and
      aspartate transaminase (AST) levels, respectively. Glucose homeostasis was
      evaluated by the glucose tolerance test and the liver telomere length and
      activity were measured by real time PCR and telomeric repeat amplification
      protocol (TRAP). Western blot analysis was performed to determine the expression
      level of Bcl-2, Bax and Caspase-3. Our results demonstrated that ACNAC
      supplementation improved liver pathologies of rats that received long-term HFD
      feeding. ACNAC supplementation prevented HFD-induced telomere shortening and
      improved telomerase activity. Moreover, in comparison to HFD-fed rats, ACNAC
      supplementation markedly increased the expression of Bcl-2, but significantly
      decreased the expression of Bax and Caspase-3 in juvenile rats. Together, these
      results indicate that ACNAC may be a promising choice for preventing and treating
      NAFLD among children.

PMID- 29324775
TI  - The optimal threshold of serum ceruloplasmin in the diagnosis of Wilson's
      disease: A large hospital-based study.
AB  - BACKGROUND AND AIMS: A ceruloplasmin (CP) concentration <200 mg/L is
      conventionally considered as one of the major diagnostic criteria for Wilson's
      disease (WD). However, the diagnostic accuracy of this threshold has never been
      investigated in a sufficiently large group of patients. This study aims to
      present the results of serum CP measurements in various patients and to identify
      the optimal cutoff value of CP for the diagnosis of WD. MATERIALS AND METHODS: We
      identified patients whose CP levels were evaluated from January 1, 2016 to
      December 31, 2016 using a laboratory information database. Data related to CP
      measurement were retrieved. We carefully reviewed patients' electronic medical
      records to correct errors and to obtain other necessary data. Data related to WD
      were retrieved from a special document containing medical records of patients
      with WD, which were created, modified, and maintained by authors. RESULTS: CP
      level was determined in 4048 patients (WD, 297; non-WD, 3751). The mean serum CP
      level in patients with WD was 50.6+/-44.2 mg/L, which was significantly lower
      than that in non-WD patients (293.2+/-117.3 mg/L, p<0.001). Only 1.0% of patients
      with WD had CP >=200 mg/L. The sensitivity and specificity of CP for the
      diagnosis of WD were 99.0 and 80.9%, respectively, for the conventional cutoff
      value <200 mg/L and 95.6 and 95.5%, respectively, for the cutoff value <150 mg/L;
      the latter provided a higher diagnostic accuracy for WD. 53.0% of patients with
      liver failure, 37.7% of patients with nephrotic syndrome, and 23.0% of patients
      age 1 to 6 months had serum CP <200 mg/L. Patients who were pregnant and those
      with malignant tumors, and infectious and inflammatory diseases had significantly
      higher mean serum CP levels. CONCLUSION: The optimal cutoff value of CP for the
      diagnosis of WD in China is 150 mg/L, with a sensitivity of 95.6% and specificity
      of 95.5%, thereby providing the highest diagnostic accuracy for WD.

PMID- 29324777
TI  - Assessing an effective undergraduate module teaching applied bioinformatics to
      biology students.
AB  - Applied bioinformatics skills are becoming ever more indispensable for
      biologists, yet incorporation of these skills into the undergraduate biology
      curriculum is lagging behind, in part due to a lack of instructors willing and
      able to teach basic bioinformatics in classes that don't specifically focus on
      quantitative skill development, such as statistics or computer sciences. To help
      undergraduate course instructors who themselves did not learn bioinformatics as
      part of their own education and are hesitant to plunge into teaching big data
      analysis, a module was developed that is written in plain-enough language, using
      publicly available computing tools and data, to allow novice instructors to teach
      next-generation sequence analysis to upper-level undergraduate students. To
      determine if the module allowed students to develop a better understanding of and
      appreciation for applied bioinformatics, various tools were developed and
      employed to assess the impact of the module. This article describes both the
      module and its assessment. Students found the activity valuable for their
      education and, in focus group discussions, emphasized that they saw a need for
      more and earlier instruction of big data analysis as part of the undergraduate
      biology curriculum.

PMID- 29324776
TI  - Effect of a lifestyle intervention in obese infertile women on cardiometabolic
      health and quality of life: A randomized controlled trial.
AB  - BACKGROUND: The prevalence of obesity, an important cardiometabolic risk factor,
      is rising in women. Lifestyle improvements are the first step in treatment of
      obesity, but the success depends on factors like timing and motivation. Women are
      especially receptive to advice about lifestyle before and during pregnancy.
      Therefore, we hypothesize that the pre-pregnancy period provides the perfect
      window of opportunity to improve cardiometabolic health and quality of life of
      obese infertile women, by means of a lifestyle intervention. METHODS AND
      FINDINGS: Between 2009-2012, 577 infertile women between 18 and 39 years of age,
      with a Body Mass Index of >= 29 kg/m2, were randomized to a six month lifestyle
      intervention preceding infertility treatment, or to direct infertility treatment.
      The goal of the intervention was 5-10% weight loss or a BMI < 29 kg/m2.
      Cardiometabolic outcomes included weight, waist- and hip circumference, body mass
      index, systolic and diastolic blood pressure, fasting glucose and insulin, HOMA
      IR, hs-CRP, lipids and metabolic syndrome. All outcomes were measured by research
      nurses at randomization, 3 and 6 months. Self-reported quality of life was also
      measured at 12 months. Three participants withdrew their informed consent, and 63
      participants discontinued the intervention program. Intention to treat analysis
      was conducted. Mixed effects regression models analyses were performed. Results
      are displayed as estimated mean differences between intervention and control
      group. Weight (-3.1 kg 95% CI: -4.0 to -2.2 kg; P < .001), waist circumference (
      2.4 cm 95% CI: -3.6 to -1.1 cm; P < .001), hip circumference (-3.0 95% CI: -4.2
      to -1.9 cm; P < .001), BMI (-1.2 kg/m2 95% CI: -1.5 to -0.8 kg/m2; P < .001),
      systolic blood pressure (-2.8 mmHg 95% CI: -5.0 to -0.7 mmHg; P = .01) and HOMA
      IR (-0.5 95% CI: -0.8 to -0.1; P = .01) were lower in the intervention group
      compared to controls. Hs-CRP and lipids did not differ between groups. The odds
      ratio for metabolic syndrome in the intervention group was 0.53 (95% CI: 0.33 to
      0.85; P < .01) compared to controls. Physical QoL scores were higher in the
      lifestyle intervention group (2.2 95% CI: 0.9 to 3.5; P = .001) while mental QoL
      scores did not differ. CONCLUSIONS: In obese infertile women, a lifestyle
      intervention prior to infertility treatment improves cardiometabolic health and
      self-reported physical quality of life (LIFEstyle study: Netherlands Trial
      Register: NTR1530).

PMID- 29324779
TI  - Filling gaps in bacterial amino acid biosynthesis pathways with high-throughput
      genetics.
AB  - For many bacteria with sequenced genomes, we do not understand how they
      synthesize some amino acids. This makes it challenging to reconstruct their
      metabolism, and has led to speculation that bacteria might be cross-feeding amino
      acids. We studied heterotrophic bacteria from 10 different genera that grow
      without added amino acids even though an automated tool predicts that the
      bacteria have gaps in their amino acid synthesis pathways. Across these bacteria,
      there were 11 gaps in their amino acid biosynthesis pathways that we could not
      fill using current knowledge. Using genome-wide mutant fitness data, we
      identified novel enzymes that fill 9 of the 11 gaps and hence explain the
      biosynthesis of methionine, threonine, serine, or histidine by bacteria from six
      genera. We also found that the sulfate-reducing bacterium Desulfovibrio vulgaris
      synthesizes homocysteine (which is a precursor to methionine) by using DUF39,
      NIL/ferredoxin, and COG2122 proteins, and that homoserine is not an intermediate
      in this pathway. Our results suggest that most free-living bacteria can likely
      make all 20 amino acids and illustrate how high-throughput genetics can uncover
      previously-unknown amino acid biosynthesis genes.

PMID- 29324778
TI  - Genetic diversity and recombination of enterovirus G strains in Japanese pigs:
      High prevalence of strains carrying a papain-like cysteine protease sequence in
      the enterovirus G population.
AB  - To study the genetic diversity of enterovirus G (EV-G) among Japanese pigs,
      metagenomics sequencing was performed on fecal samples from pigs with or without
      diarrhea, collected between 2014 and 2016. Fifty-nine EV-G sequences, which were
      >5,000 nucleotides long, were obtained. By complete VP1 sequence analysis,
      Japanese EV-G isolates were classified into G1 (17 strains), G2 (four strains),
      G3 (22 strains), G4 (two strains), G6 (two strains), G9 (six strains), G10 (five
      strains), and a new genotype (one strain). Remarkably, 16 G1 and one G2 strain
      identified in diarrheic (23.5%; four strains) or normal (76.5%; 13 strains) fecal
      samples possessed a papain-like cysteine protease (PL-CP) sequence, which was
      recently found in the USA and Belgium in the EV-G genome, at the 2C-3A junction
      site. This paper presents the first report of the high prevalence of viruses
      carrying PL-CP in the EV-G population. Furthermore, possible inter- and
      intragenotype recombination events were found among EV-G strains, including G1-PL
      CP strains. Our findings may advance the understanding of the molecular
      epidemiology and genetic evolution of EV-Gs.

PMID- 29324780
TI  - Methods for sampling geographically mobile female traders in an East African
      market setting.
AB  - BACKGROUND: The role of migration in the spread of HIV in sub-Saharan Africa is
      well-documented. Yet migration and HIV research have often focused on HIV risks
      to male migrants and their partners, or migrants overall, often failing to
      measure the risks to women via their direct involvement in migration.
      Inconsistent measures of mobility, gender biases in those measures, and limited
      data sources for sex-specific population-based estimates of mobility have
      contributed to a paucity of research on the HIV prevention and care needs of
      migrant and highly mobile women. This study addresses an urgent need for novel
      methods for developing probability-based, systematic samples of highly mobile
      women, focusing on a population of female traders operating out of one of the
      largest open air markets in East Africa. Our method involves three stages: 1.)
      identification and mapping of all market stall locations using Global Positioning
      System (GPS) coordinates; 2.) using female market vendor stall GPS coordinates to
      build the sampling frame using replicates; and 3.) using maps and GPS data for
      recruitment of study participants. RESULTS: The location of 6,390 vendor stalls
      were mapped using GPS. Of these, 4,064 stalls occupied by women (63.6%) were used
      to draw four replicates of 128 stalls each, and a fifth replicate of 15 pre
      selected random alternates for a total of 527 stalls assigned to one of five
      replicates. Staff visited 323 stalls from the first three replicates and from
      these successfully recruited 306 female vendors into the study for a
      participation rate of 94.7%. Mobilization strategies and involving traders
      association representatives in participant recruitment were critical to the
      study's success. CONCLUSION: The study's high participation rate suggests that
      this geospatial sampling method holds promise for development of probability
      based samples in other settings that serve as transport hubs for highly mobile
      populations.

PMID- 29324781
TI  - Neuraminidase inhibitor susceptibility and neuraminidase enzyme kinetics of human
      influenza A and B viruses circulating in Thailand in 2010-2015.
AB  - Amino acid substitutions within or near the active site of the viral
      neuraminidase (NA) may affect influenza virus fitness. In influenza A(H3N2) and B
      viruses circulating in Thailand between 2010 and 2015, we identified several NA
      substitutions that were previously reported to be associated with reduced
      inhibition by NA inhibitors (NAIs). To study the effect of these substitutions on
      the enzymatic properties of NA and on virus characteristics, we generated
      recombinant influenza viruses possessing either a wild type (WT) NA or an NA with
      a single I222V, S331G, or S331R substitution [in influenza A(H3N2) viruses] or a
      single D342S, A395T, A395V, or A395D NA substitution (in influenza B viruses). We
      generated recombinant (7:1) influenza A and B viruses on the genetic background
      of A/Puerto Rico/8/1934 (A/PR/8, H1N1) or B/Yamanashi/166/1998 (B/YAM) viruses,
      respectively. In contrast to the expected phenotypes, all the recombinant
      influenza A(H3N2) and B viruses carrying putative NA resistance substitutions
      were susceptible to NAIs. The Km and Vmax for the NAs of A/PR8-S331G and A/PR8
      S331R viruses were higher than for the NA of WT virus, and the corresponding
      values for the B/YAM-D342S virus were lower than for the NA of WT virus. Although
      there was initial variation in the kinetics of influenza A and B viruses'
      replication in MDCK cells, their titers were comparable to each other and to WT
      viruses at later time points. All introduced substitutions were stable except for
      B/YAM-D342S and B/YAM-A395V which reverted to WT sequences after three passages.
      Our data suggest that inferring susceptibility to NAIs based on sequence
      information alone should be cautioned. The impact of NA substitution on NAI
      resistance, viral growth, and enzymatic properties is viral context dependent and
      should be empirically determined.

PMID- 29324782
TI  - MAFB is dispensable for the fetal testis morphogenesis and the maintenance of
      spermatogenesis in adult mice.
AB  - The transcription factor MAFB is an important regulator of the development and
      differentiation of various organs and tissues. Previous studies have shown that
      MAFB is expressed in embryonic and adult mouse testes and is expected to act as
      the downstream target of retinoic acid (RA) to initiate spermatogenesis. However,
      its exact localization and function remain unclear. Here, we localized MAFB
      expression in embryonic and adult testes and analyzed its gene function using
      Mafb-deficient mice. We found that MAFB and c-MAF are the only large MAF
      transcription factors expressed in testes, while MAFA and NRL are not. MAFB was
      localized in Leydig and Sertoli cells at embryonic day (E) 18.5 but in Leydig
      cells, Sertoli cells, and pachytene spermatocytes in adults. Mafb-deficient
      testes at E18.5 showed fully formed seminiferous tubules with no abnormal
      structure or differences in testicular somatic cell numbers compared with those
      of control wild-type mice. Additionally, the expression levels of genes related
      to development and function of testicular cells were unchanged between genotypes.
      In adults, the expression of MAFB in Sertoli cells was shown to be stage specific
      and induced by RA. By generating Mafbfl/fl CAG-CreERTM (Mafb-cKO) mice, in which
      Cre recombinase was activated upon tamoxifen treatment, we found that the
      neonatal cKO mice died shortly upon Mafb deletion, but adult cKO mice were alive
      upon deletion. Adult cKO mice were fertile, and spermatogenesis maintenance was
      normal, as indicated by histological analysis, hormone levels, and germ cell
      stage-specific markers. Moreover, there were no differences in the proportion of
      seminiferous stages between cKO mice and controls. However, RNA-Seq analysis of
      cKO Sertoli cells revealed that the down-regulated genes were related to immune
      function and phagocytosis activity but not spermatogenesis. In conclusion, we
      found that MAFB is dispensable for fetal testis morphogenesis and spermatogenesis
      maintenance in adult mice, despite the significant gene expression in different
      cell types, but MAFB might be critical for phagocytosis activity of Sertoli
      cells.

PMID- 29324784
TI  - Multiscale modelling of blood flow in cerebral microcirculation: Details at
      capillary scale control accuracy at the level of the cortex.
AB  - Aging or cerebral diseases may induce architectural modifications in human brain
      microvascular networks, such as capillary rarefaction. Such modifications limit
      blood and oxygen supply to the cortex, possibly resulting in energy failure and
      neuronal death. Modelling is key in understanding how these architectural
      modifications affect blood flow and mass transfers in such complex networks.
      However, the huge number of vessels in the human brain-tens of billions-prevents
      any modelling approach with an explicit architectural representation down to the
      scale of the capillaries. Here, we introduce a hybrid approach to model blood
      flow at larger scale in the brain microcirculation, based on its multiscale
      architecture. The capillary bed, which is a space-filling network, is treated as
      a porous medium and modelled using a homogenized continuum approach. The larger
      arteriolar and venular trees, which cannot be homogenized because of their
      fractal-like nature, are treated as a network of interconnected tubes with a
      detailed representation of their spatial organization. The main contribution of
      this work is to devise a proper coupling model at the interface between these two
      components. This model is based on analytical approximations of the pressure
      field that capture the strong pressure gradients building up in the capillaries
      connected to arterioles or venules. We evaluate the accuracy of this model for
      both very simple architectures with one arteriole and/or one venule and for more
      complex ones, with anatomically realistic tree-like vessels displaying a large
      number of coupling sites. We show that the hybrid model is very accurate in
      describing blood flow at large scales and further yields a significant
      computational gain by comparison with a classical network approach. It is
      therefore an important step towards large scale simulations of cerebral blood
      flow and lays the groundwork for introducing additional levels of complexity in
      the future.

PMID- 29324783
TI  - SIRT3 activator Honokiol attenuates beta-Amyloid by modulating amyloidogenic
      pathway.
AB  - Honokiol (poly-phenolic lignan from Magnolia grandiflora) is a Sirtuin-3 (SIRT3)
      activator which exhibit antioxidant activity and augment mitochondrial functions
      in several experimental models. Modern evidence suggests the critical role of
      SIRT3 in the progression of several metabolic and neurodegenerative diseases.
      Amyloid beta (Abeta), the precursor to extracellular senile plaques, accumulates
      in the brains of patients with Alzheimer's disease (AD) and is related to the
      development of cognitive impairment and neuronal cell death. Abeta is generated
      from amyloid-beta precursor protein (APP) through sequential cleavages, first by
      beta-secretase and then by gamma-secretase. Drugs modulating this pathway are
      believed to be one of the most promising strategies for AD treatment. In the
      present study, we found that Honokiol significantly enhanced SIRT3 expression,
      reduced reactive oxygen species generation and lipid peroxidation, enhanced
      antioxidant activities, and mitochondrial function thereby reducing Abeta and
      sAPPbeta levels in Chinese Hamster Ovarian (CHO) cells (carrying the amyloid
      precursor protein-APP and Presenilin PS1 mutation). Mechanistic studies revealed
      that Honokiol affects neither protein levels of APP nor alpha-secretase activity.
      In contrast, Honokiol increased the expression of AMPK, CREB, and PGC-1alpha,
      thereby inhibiting beta-secretase activity leading to reduced Abeta levels. These
      results suggest that Honokiol is an activator of SIRT3 capable of improving
      antioxidant activity, mitochondrial energy regulation, while decreasing Abeta,
      thereby indicating it to be a lead compound for AD drug development.

PMID- 29324785
TI  - Phylogenetic diversity, antimicrobial susceptibility and virulence gene profiles
      of Brachyspira hyodysenteriae isolates from pigs in Germany.
AB  - Swine dysentery (SD) is an economically important diarrheal disease in pigs
      caused by different strongly hemolytic Brachyspira (B.) species, such as B.
      hyodysenteriae, B. suanatina and B. hampsonii. Possible associations of
      epidemiologic data, such as multilocus sequence types (STs) to virulence gene
      profiles and antimicrobial susceptibility are rather scarce, particularly for B.
      hyodysenteriae isolates from Germany. In this study, B. hyodysenteriae (n = 116)
      isolated from diarrheic pigs between 1990 and 2016 in Germany were investigated
      for their STs, susceptibility to the major drugs used for treatment of SD
      (tiamulin and valnemulin) and genes that were previously linked with virulence
      and encode for hemolysins (tlyA, tlyB, tlyC, hlyA, BHWA1_RS02885, BHWA1_RS09085,
      BHWA1_RS04705, and BHWA1_RS02195), outer membrane proteins (OMPs) (bhlp16,
      bhlp17.6, bhlp29.7, bhmp39f, and bhmp39h) as well as iron acquisition factors
      (ftnA and bitC). Multilocus sequence typing (MLST) revealed that 79.4% of the
      isolates belonged to only three STs, namely ST52 (41.4%), ST8 (12.1%), and ST112
      (25.9%) which have been observed in other European countries before. Another 24
      isolates belonged to twelve new STs (ST113-118, ST120-123, ST131, and ST193). The
      temporal distribution of STs revealed the presence of new STs as well as the
      regular presence of ST52 over three decades (1990s-2000s). The proportion of
      strains that showed resistance to both tiamulin und valnemulin (39.1%) varied
      considerably among the most frequent STs ranging from 0% (0/14 isolates
      resistant) in ST8 isolates to 46.7% (14/30), 52.1% (25/48), and 85.7% (6/7) in
      isolates belonging to ST112, ST52, and ST114, respectively. All hemolysin genes
      as well as the iron-related gene ftnA and the OMP gene bhlp29.7 were regularly
      present in the isolates, while the OMP genes bhlp17.6 and bhmp39h could not be
      detected. Sequence analysis of hemolysin genes of selected isolates revealed co
      evolution of tlyB, BHWA1_RS02885, BHWA1_RS09085, and BHWA1_RS02195 with the core
      genome and suggested independent evolution of tlyA, tlyC, and hlyA. Our data
      indicate that in Germany, swine dysentery might be caused by a limited number of
      B. hyodysenteriae clonal groups. Major STs (ST8, ST52, and ST112) are shared with
      other countries in Europe suggesting a possible role of the European intra
      Community trade of pigs in the dissemination of certain clones. The
      identification of several novel STs, some of which are single or double locus
      variants of ST52, may on the other hand hint towards an ongoing diversification
      of the pathogen in the studied area. The linkage of pleuromutilin susceptibility
      and sequence type of an isolate might reflect a clonal expansion of the
      underlying resistance mechanism, namely mutations in the ribosomal RNA genes. A
      linkage between single virulence-associated genes (VAGs) or even VAG patterns and
      the phylogenetic background of the isolates could not be established, since
      almost all VAGs were regularly present in the isolates.

PMID- 29324786
TI  - Controlled potential electro-oxidation of genomic DNA.
AB  - Exposure of mammalian cells to oxidative stress can result in DNA damage that
      adversely affects many cell processes. Lack of dependable DNA damage reference
      materials and standardized measurement methods, despite many case-control studies
      hampers the wider recognition of the link between oxidatively degraded DNA and
      disease risk. We used bulk electrolysis in an electrochemical system and gas
      chromatographic mass spectrometric analysis (GC/MS/MS) to control and measure,
      respectively, the effect of electrochemically produced reactive oxygen species on
      calf thymus DNA (ct-DNA). DNA was electro-oxidized for 1 h at four fixed
      oxidizing potentials (E = 0.5 V, 1.0 V, 1.5 V and 2 V (vs Ag/AgCl)) using a high
      surface area boron-doped diamond (BDD) working electrode (WE) and the resulting
      DNA damage in the form of oxidatively-modified DNA lesions was measured using
      GC/MS/MS. We have shown that there are two distinct base lesion formation modes
      in the explored electrode potential range, corresponding to 0.5 V < E < 1.5 V and
      E > 1.5 V. Amounts of all four purine lesions were close to a negative control
      levels up to E = 1.5 V with evidence suggesting higher levels at the lowest
      potential of this range (E = 0.5 V). A rapid increase in all base lesion yields
      was measured when ct-DNA was exposed at E = 2 V, the potential at which hydroxyl
      radicals were efficiently produced by the BDD electrode. The present results
      demonstrate that controlled potential preparative electrooxidation of double
      stranded DNA can be used to purposely increase the levels of oxidatively modified
      DNA lesions in discrete samples. It is envisioned that these DNA samples may
      potentially serve as analytical control or quality assurance reference materials
      for the determination of oxidatively induced DNA damage.

PMID- 29324787
TI  - Association of sex hormones with physical, laboratory, and imaging markers of
      anthropometry in men and women from the general population.
AB  - OBJECTIVES: The aim of this study was to evaluate the association of sex hormones
      with anthropometry in a large population-based cohort, with liquid chromatography
      mass spectrometry (LCMS)-based sex hormone measurements and imaging markers.
      STUDY DESIGN/MAIN OUTCOME MEASURES: Cross-sectional data from 957 men and women
      from the population-based Study of Health in Pomerania (SHIP) were used.
      Associations of a comprehensive panel of LCMS-measured sex hormones with
      anthropometric parameters, laboratory, and imaging markers were analyzed in
      multivariable regression models for the full sample and stratified by sex. Sex
      hormone measures included total testosterone (TT), free testosterone (fT),
      estrone and estradiol, androstenedione (ASD), dehydroepiandrosterone sulfate
      (DHEAS), and sex hormone-binding globulin (SHBG). Domains of anthropometry
      included physical measures (body-mass-index (BMI), waist circumference, waist-to
      height-ratio, waist-to-hip-ratio, and hip circumference), laboratory measures of
      adipokines (leptin and vaspin), and magnet resonance imaging-based measures
      (visceral and subcutaneous adipose tissue). RESULTS: In men, inverse associations
      between all considered anthropometric parameters with TT were found: BMI (beta
      coefficient, standard error (SE): -0.159, 0.037), waist-circumference (beta
      coefficient, SE: -0.892, 0.292), subcutaneous adipose tissue (beta-coefficient,
      SE: -0.156, 0.023), and leptin (beta-coefficient, SE: -0.046, 0.009). In women TT
      (beta-coefficient, SE: 1.356, 0.615) and estrone (beta-coefficient, SE: 0.014,
      0.005) were positively associated with BMI. In analyses of variance, BMI and
      leptin were inversely associated with TT, ASD, and DHEAS in men, but positively
      associated with estrone. In women, BMI and leptin were positively associated with
      all sex hormones. CONCLUSION: The present population-based study confirmed and
      extended previously reported sex-specific associations between sex hormones and
      various anthropometric markers of overweight and obesity.

PMID- 29324788
TI  - Esrp1 is a marker of mouse fetal germ cells and differentially expressed during
      spermatogenesis.
AB  - ESRP1 regulates alternative splicing, producing multiple transcripts from its
      target genes in epithelial tissues. It is upregulated during mesenchymal to
      epithelial transition associated with reprogramming of fibroblasts to iPS cells
      and has been linked to pluripotency. Mouse fetal germ cells are the founders of
      the adult gonadal lineages and we found that Esrp1 mRNA was expressed in both
      male and female germ cells but not in gonadal somatic cells at various stages of
      gonadal development (E12.5-E15.5). In the postnatal testis, Esrp1 mRNA was highly
      expressed in isolated cell preparations enriched for spermatogonia but expressed
      at lower levels in those enriched for pachytene spermatocytes and round
      spermatids. Co-labelling experiments with PLZF and c-KIT showed that ESRP1 was
      localized to nuclei of both Type A and B spermatogonia in a speckled pattern, but
      was not detected in SOX9+ somatic Sertoli cells. No co-localization with the
      nuclear speckle marker, SC35, which has been associated with post-transcriptional
      splicing, was observed, suggesting that ESRP1 may be associated with co
      transcriptional splicing or have other functions. RNA interference mediated
      knockdown of Esrp1 expression in the seminoma-derived Tcam-2 cell line
      demonstrated that ESRP1 regulates alternative splicing of mRNAs in a non
      epithelial cell germ cell tumour cell line.

PMID- 29324789
TI  - An L213A variant of beta-glycosidase from Sulfolobus solfataricus with increased
      alpha-L-arabinofuranosidase activity converts ginsenoside Rc to compound K.
AB  - Compound K (C-K) is a crucial pharmaceutical and cosmetic component because of
      disease prevention and skin anti-aging effects. For industrial application of
      this active compound, the protopanaxadiol (PPD)-type ginsenosides should be
      transformed to C-K. beta-Glycosidase from Sulfolobus solfataricus has been
      reported as an efficient C-K-producing enzyme, using glycosylated PPD-type
      ginsenosides as substrates. beta-Glycosidase from S. solfataricus can hydrolyze
      beta-d-glucopyranoside in ginsenosides Rc, C-Mc1, and C-Mc, but not alpha-l
      arabinofuranoside in these ginsenosides. To determine candidate residues involved
      in alpha-l-arabinofuranosidase activity, compound Mc (C-Mc) was docking to beta
      glycosidase from S. solfataricus in homology model and sequence was aligned with
      beta-glycosidase from Pyrococcus furiosus that has alpha-l-arabinofuranosidase
      activity. A L213A variant beta-glycosidase with increased alpha-l
      arabinofuranosidase activity was selected by substitution of other amino acids
      for candidate residues. The increased alpha-l-arabinofuranosidase activity of the
      L213A variant was confirmed through the determination of substrate specificity,
      change in binding energy, transformation pathway, and C-K production from
      ginsenosides Rc and C-Mc. The L213A variant beta-glycosidase catalyzed the
      conversion of Rc to Rd by hydrolyzing alpha-l-arabinofuranoside linked to Rc,
      whereas the wild-type beta-glycosidase did not. The variant enzyme converted
      ginsenosides Rc and C-Mc into C-K with molar conversions of 97%, which were 1.5-
      and 2-fold higher, respectively, than those of the wild-type enzyme. Therefore,
      protein engineering is a useful tool for enhancing the hydrolytic activity on
      specific glycoside linked to ginsenosides.

PMID- 29324790
TI  - Frog size on continental islands of the coast of Rio de Janeiro and the
      generality of the Island Rule.
AB  - Island Rule postulated that individuals on islands tend to dwarfism when
      individuals from mainland populations are large and to gigantism when mainland
      populations present small individuals. There has been much discussion about this
      rule, but only few studies were carried out aiming to reveal this pattern for
      anurans. Our study focused on measuring the size of individuals on islands and to
      find a possible pattern of size modification for insular anurans. Individuals
      were collected on continental islands, measured and compared to mainland
      populations. We selected four species with different natural history aspects
      during these analyses. Island parameters were compared to size of individuals in
      order to find an explanation to size modification. Three of the four species
      presented size shifting on islands. Ololygon trapicheiroi and Adenomera marmorata
      showed dwarfism, Boana albomarginata showed gigantism and in Thoropa miliaris
      there was no evident size modification. Allometric analysis also revealed
      differential modification, which might be a result of different selective
      pressures on islands in respect of mainland populations. Regression model
      explained most of the size modification in B. albomarginata, but not for the
      other species. Our results indicate that previous assumptions, usually proposed
      for mammals from older islands, do not fit to the anurans studied here. We
      support the assumption that size modification on islands are population-specific.
      Hence, in B. albomarginata some factor associated to competition, living area and
      isolation time might likely be responsible for gigantism on islands.

PMID- 29324791
TI  - Sediment biomarkers elucidate the Holocene ontogeny of a shallow lake.
AB  - We carried out geochemical analyses on a sediment core from Lake Harris, Florida
      (USA) to identify sources of organic matter to the sediment throughout the
      Holocene, and relate changes in those sources to shifts in past climate and
      environmental conditions. We hypothesized that the sources of organic matter
      changed in response to regional hydrologic shifts following de-glaciation, and to
      human population expansion in the state during the 20th century. Hydroclimate
      shifts in Florida were related to: 1) a steady rise in relative sea level and the
      fresh water table that began in the early Holocene, 2) wetland formation and
      expansion ca. 5,000 cal yrs BP, and 3) the onset of the modern El Nino (ENSO)
      cycle ~3,000 cal yrs BP. Stratigraphic changes in sediment variables from Lake
      Harris reflect each of these hydroclimate periods. Early in the Holocene, Lake
      Harris was a marsh-like system in a relatively dry, open-prairie environment.
      Organic sediments deposited at that time were derived largely from terrestrial
      sources, as inferred from high TOC/TN ratios, a dominance of longer-chain of n
      alkanes (n-C29-31), relatively negative organic carbon isotope values
      (delta13CTOC), and low biogenic silica concentrations. In the middle Holocene, a
      positive shift in delta13CTOC coincided with the onset of wetter conditions in
      Florida. Submerged macrophyte biomarkers (n-C21-23) dominated, and during that
      period bulk organic carbon isotope values were most similar to delta13C values of
      mid-chain-length n-alkanes. In the late Holocene, delta13CTOC values declined,
      CaCO3 levels decreased to trace amounts, organic carbon concentrations increased
      and diatom biogenic silica concentrations increased from 10 to 120 mg g-1. Around
      2,900 cal yrs BP, the effects of ENSO intensified and many Florida lakes deepened
      to their current limnetic state. Concentrations of algal and cyanobacterial
      biomarkers in the Lake Harris core increased by orders of magnitude after about
      AD 1940, in response to human-induced eutrophication, an inference supported by
      values of delta15N that fluctuate around zero.

PMID- 29324792
TI  - Critical evaluation of colon submucosal microdialysis in awake, mobile rats.
AB  - Sensors able to record large bowel physiology and biochemistry in situ in awake
      rodents are lacking. Microdialysis is a mini-invasive technique that may be
      utilized to continuously deliver or recover low-molecular substances from various
      tissues. In this experiment we evaluated the feasibility of in vivo microdialysis
      to monitor extracellular fluid chemistry in the descending colon submucosa of
      conscious, freely moving rodents. Following surgical implantation of a
      microdialysis probe, male Wistar rats were housed in metabolic cages where they
      were analgized and clinically followed for four days with free access to standard
      diet and water. To assess local microcirculation and probe function, glucose,
      lactate, glucose-to-lactate ratio and urea clearance were determined in the
      dialysates from the three postoperative days with focus on the final 24-h period.
      In an attempt to mitigate the expected tissue inflammatory response, one group of
      animals had the catheters perfused with 5-aminosalicylic acid-enriched medium
      with final concentration 1 MUmol/L. For verification of probe position and the
      assessment of the surrounding foreign body reaction, standard histological and
      immunohistochemical methods were employed. Microdialysis of rat gut is associated
      with considerable technical challenges that may lead to the loss of probe
      function and high drop-out rate. In this setting, limited data did not allow to
      draw any firm conclusion regarding local anti-inflammatory effectiveness of 5
      aminosalicylic acid perfusion. Although intestinal microdialysis may be suitable
      for larger anesthetized animals, low reproducibility of the presented method
      compromises its routine experimental use in awake and freely moving small-sized
      rodents.

PMID- 29324793
TI  - Phylogeography of screaming hairy armadillo Chaetophractus vellerosus: Successive
      disjunctions and extinctions due to cyclical climatic changes in southern South
      America.
AB  - Little is known about phylogeography of armadillo species native to southern
      South America. In this study we describe the phylogeography of the screaming
      hairy armadillo Chaetophractus vellerosus, discuss previous hypothesis about the
      origin of its disjunct distribution and propose an alternative one, based on
      novel information on genetic variability. Variation of partial sequences of
      mitochondrial DNA Control Region (CR) from 73 individuals from 23 localities were
      analyzed to carry out a phylogeographic analysis using neutrality tests, mismatch
      distribution, median-joining (MJ) network and paleontological records. We found
      17 polymorphic sites resulting in 15 haplotypes. Two new geographic records that
      expand known distribution of the species are presented; one of them links the
      distributions of recently synonimized species C. nationi and C. vellerosus.
      Screaming hairy armadillo phylogeographic pattern can be addressed as category V
      of Avise: common widespread linages plus closely related lineages confined to one
      or a few nearby locales each. The older linages are distributed in the north
      central area of the species distribution range in Argentina (i.e. ancestral area
      of distribution). C. vellerosus seems to be a low vagility species that expanded,
      and probably is expanding, its distribution range while presents signs of genetic
      structuring in central areas. To explain the disjunct distribution, a hypothesis
      of extinction of the species in intermediate areas due to quaternary climatic
      shift to more humid conditions was proposed. We offer an alternative explanation:
      long distance colonization, based on null genetic variability, paleontological
      record and evidence of alternance of cold/arid and temperate/humid climatic
      periods during the last million years in southern South America.

PMID- 29324794
TI  - Real-time positioning in logging: Effects of forest stand characteristics,
      topography, and line-of-sight obstructions on GNSS-RF transponder accuracy and
      radio signal propagation.
AB  - Real-time positioning on mobile devices using global navigation satellite system
      (GNSS) technology paired with radio frequency (RF) transmission (GNSS-RF) may
      help to improve safety on logging operations by increasing situational awareness.
      However, GNSS positional accuracy for ground workers in motion may be reduced by
      multipath error, satellite signal obstruction, or other factors. Radio
      propagation of GNSS locations may also be impacted due to line-of-sight (LOS)
      obstruction in remote, forested areas. The objective of this study was to
      characterize the effects of forest stand characteristics, topography, and other
      LOS obstructions on the GNSS accuracy and radio signal propagation quality of
      multiple Raveon Atlas PT GNSS-RF transponders functioning as a network in a range
      of forest conditions. Because most previous research with GNSS in forestry has
      focused on stationary units, we chose to analyze units in motion by evaluating
      the time-to-signal accuracy of geofence crossings in 21 randomly-selected stands
      on the University of Idaho Experimental Forest. Specifically, we studied the
      effects of forest stand characteristics, topography, and LOS obstructions on (1)
      the odds of missed GNSS-RF signals, (2) the root mean squared error (RMSE) of
      Atlas PTs, and (3) the time-to-signal accuracy of safety geofence crossings in
      forested environments. Mixed-effects models used to analyze the data showed that
      stand characteristics, topography, and obstructions in the LOS affected the odds
      of missed radio signals while stand variables alone affected RMSE. Both stand
      characteristics and topography affected the accuracy of geofence alerts.

PMID- 29324795
TI  - Nanodiamonds facilitate killing of intracellular uropathogenic E. coli in an in
      vitro model of urinary tract infection pathogenesis.
AB  - About 25-44% of women will experience at least one episode of recurrent UTI and
      the causative agent in over 70% of UTI cases is uropathogenic Escherichia coli
      (UPEC). UPEC cause recurrent UTI by evading the bladder's innate immune system
      through internalization into the bladder epithelium where antibiotics cannot
      reach or be effective. Thus, it is important to develop novel therapeutics to
      eliminate these intracellular pathogens. Nanodiamonds (NDs) are biocompatible
      nanomaterials that serve as promising candidates for targeted therapeutic
      applications. The objective of the current study was to investigate if 6 or 25 nm
      NDs can kill extracellular and intracellular UPEC in infected bladder cells. We
      utilized the human bladder epithelial cell line, T24, and an invasive strain of
      UPEC that causes recurrent UTI. We found that acid-purified 6 nm NDs displayed
      greater antibacterial properties towards UPEC than 25 nm NDs (11.5% vs 94.2%
      CFU/mL at 100 MUg/mL of 6 and 25 nm, respectively; P<0.001). Furthermore, 6 nm
      NDs were better than 25 nm NDs in reducing the number of UPEC internalized in T24
      bladder cells (46.1% vs 81.1% CFU/mL at 100 MUg/mL of 6 and 25 nm, respectively;
      P<0.01). Our studies demonstrate that 6 nm NDs interacted with T24 bladder cells
      in a dose-dependent manner and were internalized in 2 hours through an actin
      dependent mechanism. Finally, internalization of NDs was required for reducing
      the number of intracellular UPEC in T24 bladder cells. These findings suggest
      that 6 nm NDs are promising candidates to treat recurrent UTIs.

PMID- 29324796
TI  - Quercetin and aconitine synergistically induces the human cervical carcinoma HeLa
      cell apoptosis via endoplasmic reticulum (ER) stress pathway.
AB  - Up till now, studies have not been conducted on how the combination of Quercetin
      (Q), Aconitine (A) and apoptosis induction affects human cervical carcinoma HeLa
      cells. The result of our findings shows that the combination of Q and A (QA) is
      capable of synergistically inhibiting the proliferation of HeLa cells in a number
      of concentrations. QA synergistically inhibits the proliferation of MDR1 gene in
      the HeLa cells. It is concluded based on our result that QA induces apoptosis and
      ER stress just as QA-induced ER stress pathway may mediate apoptosis by
      upregulating mRNA expression levels of eIF2alpha, ATF4, IRE1, XBP1, ATF6, PERK
      and CHOP in the HeLa cells. The up-regulating of mRNA expression level of GRP78
      and activation of UPR are a molecular basis of QA-induced ER stress.

PMID- 29324799
TI  - Comprehensive untargeted metabolomics of Lychnnophorinae subtribe (Asteraceae:
      Vernonieae) in a phylogenetic context.
AB  - Members of the subtribe Lychnophorinae occur mostly within the Cerrado domain of
      the Brazilian Central Plateau. The relationships between its 11 genera, as well
      as between Lychnophorinae and other subtribes belonging to the tribe Vernonieae,
      have recently been investigated upon a phylogeny based on molecular and
      morphological data. We report the use of a comprehensive untargeted metabolomics
      approach, combining HPLC-MS and GC-MS data, followed by multivariate analyses
      aiming to assess the congruence between metabolomics data and the phylogenetic
      hypothesis, as well as its potential as a chemotaxonomic tool. We analyzed 78
      species by UHPLC-MS and GC-MS in both positive and negative ionization modes. The
      metabolic profiles obtained for these species were treated in MetAlign and in
      MSClust and the matrices generated were used in SIMCA for hierarchical cluster
      analyses, principal component analyses and orthogonal partial least square
      discriminant analysis. The results showed that metabolomic analyses are mostly
      congruent with the phylogenetic hypothesis especially at lower taxonomic levels
      (Lychnophora or Eremanthus). Our results confirm that data generated using
      metabolomics provide evidence for chemotaxonomical studies, especially for
      phylogenetic inference of the Lychnophorinae subtribe and insight into the
      evolution of the secondary metabolites of this group.

PMID- 29324797
TI  - Sex-dependent impact of early-life stress and adult immobilization in the
      attribution of incentive salience in rats.
AB  - Early life stress (ELS) induces long-term effects in later functioning and
      interacts with further exposure to other stressors in adulthood to shape our
      responsiveness to reward-related cues. The attribution of incentive salience to
      food-related cues may be modulated by previous and current exposures to stressors
      in a sex-dependent manner. We hypothesized from human data that exposure to a
      traumatic (severe) adult stressor will decrease the attribution of incentive
      salience to reward-associated cues, especially in females, because these effects
      are modulated by previous ELS. To study these factors in Long-Evans rats, we used
      as an ELS model of restriction of nesting material and concurrently evaluated
      maternal care. In adulthood, the offspring of both sexes were exposed to acute
      immobilization (IMO), and several days after, a Pavlovian conditioning procedure
      was used to assess the incentive salience of food-related cues. Some rats
      developed more attraction to the cue predictive of reward (sign-tracking) and
      others were attracted to the location of the reward itself, the food-magazine
      (goal-tracking). Several dopaminergic markers were evaluated by in situ
      hybridization. The results showed that ELS increased maternal care and decreased
      body weight gain (only in females). Regarding incentive salience, in absolute
      control animals, females presented slightly greater sign-tracking behavior than
      males. Non-ELS male rats exposed to IMO showed a bias towards goal-tracking,
      whereas in females, IMO produced a bias towards sign-tracking. Animals of both
      sexes not exposed to IMO displayed an intermediate phenotype. ELS in IMO-treated
      females was able to reduce sign-tracking and decrease tyrosine hydroxylase
      expression in the ventral tegmental area and dopamine D1 receptor expression in
      the accumbens shell. Although the predicted greater decrease in females in sign
      tracking after IMO exposure was not corroborated by the data, the results
      highlight the idea that sex is an important factor in the study of the long-term
      impact of early and adult stressors.

PMID- 29324798
TI  - Qualitative metabolomics profiling of serum and bile from dogs with gallbladder
      mucocele formation.
AB  - Mucocele formation is characterized by secretion of abnormally thick mucus by the
      gallbladder epithelium of dogs that may cause obstruction of the bile duct or
      rupture of the gallbladder. The disease is increasingly recognized and is
      associated with a high morbidity and mortality. The cause of gallbladder mucocele
      formation in dogs is unknown. There is a strong breed predisposition and affected
      dogs have a high incidence of concurrent endocrinopathy or hyperlipidemia. These
      observations suggest a significant influence of both genetic and metabolic
      factors on disease pathogenesis. In this study, we investigated a theory that
      mucocele formation is associated with a syndrome of metabolic disruption. We
      surmised that a global, untargeted metabolomics approach could provide unique
      insight into the systemic pathogenesis of gallbladder mucocele formation and
      identify specific compounds as candidate biomarkers or treatment targets.
      Moreover, concurrent examination of the serum and hepatic duct bile metabolome
      would enable the construction of mechanism-based theories or identification of
      specific compounds responsible for altered function of the gallbladder
      epithelium. Abnormalities observed in dogs with gallbladder mucocele formation,
      including a 33-fold decrease in serum adenosine 5'-monophosphate (AMP), lower
      quantities of precursors required for synthesis of energy transporting
      nucleotides, and increases in citric acid cycle intermediates, suggest excess
      metabolic energy and a carbon surplus. Altered quantities of compounds involved
      in protein translation and RNA turnover, together with accumulation of gamma
      glutamylated and N-acetylated amino acids in serum suggest abnormal regulation of
      protein and amino acid metabolism. Increases in lathosterol and 7alpha
      hydroxycholesterol suggest a primary increase in cholesterol synthesis and
      diversion to bile acid formation. A number of specific biomarker compounds were
      identified for their ability to distinguish between control dogs and those that
      formed a gallbladder mucocele. Particularly noteworthy was a significant decrease
      in quantity of biologically active compounds that stimulate biliary ductal fluid
      secretion including adenosine, cAMP, taurolithocholic acid, and taurocholic acid.
      These findings support the presence of significant metabolic disruption in dogs
      with mucocele formation. A targeted, quantitative analysis of the identified
      serum biomarkers is warranted to determine their utility for diagnosis of this
      disease. Finally, repletion of compounds whose biological activity normally
      promotes biliary ductal secretion should be examined for any therapeutic impact
      for resolution or prevention of mucocele formation.

PMID- 29324801
TI  - Clinical characteristics and registry-validated extended pedigrees of germline
      TP53 mutation carriers in Denmark.
AB  - INTRODUCTION: TP53 mutation carrier (Li-Fraumeni Syndrome, LFS) cohort studies
      often suffer from lack of extensive pedigree exploration. METHODS: We performed a
      nation-wide exploration of TP53 mutation carrier families identified through all
      clinical genetics departments in Denmark. Pedigrees were expanded and verified
      using unique national person identification, cancer, cause of death, pathology,
      and church registries. RESULTS: We identified 30 confirmed, six obligate and 14
      assumed carriers in 15 families harboring 14 different mutations, including five
      novel and three de novo germline mutations. All but two (96%) developed cancer by
      age 54 years [mean debut age; 29.1 y., median 33.0 y., n = 26 (17F, 9M), range 1
      54 y]]. Cancer was the primary cause of all deaths [average age at death; 34.5
      years]. Two tumors were identified through registry data alone. Two independent
      families harbored novel c.80delC mutations shown to be related through an
      ancestor born in 1907. This exhaustive national collection yielded markedly fewer
      TP53 mutation carriers than the 300-1,100 expected based on estimated background
      population frequencies. CONCLUSION: Germline TP53 mutations in Denmark are likely
      to be drastically underdiagnosed despite their severe phenotype. Following recent
      advances in surveillance options of LFS patients, lack of pre-symptomatic testing
      may lead to the mismanagement of some individuals.

PMID- 29324800
TI  - Hepcidin deficiency and iron deficiency do not alter tuberculosis susceptibility
      in a murine M.tb infection model.
AB  - Tuberculosis (TB), caused by the macrophage-tropic pathogen Mycobacterium
      tuberculosis (M.tb) is a highly prevalent infectious disease. Since an immune
      correlate of protection or effective vaccine have yet to be found, continued
      research into host-pathogen interactions is important. Previous literature
      reports links between host iron status and disease outcome for many infections,
      including TB. For some extracellular bacteria, the iron regulatory hormone
      hepcidin is essential for protection against infection. Here, we investigated
      hepcidin (encoded by Hamp1) in the context of murine M.tb infection. Female
      C57BL/6 mice were infected with M.tb Erdman via aerosol. Hepatic expression of
      iron-responsive genes was measured by qRT-PCR and bacterial burden determined in
      organ homogenates. We found that hepatic Hamp1 mRNA levels decreased post
      infection, and correlated with a marker of BMP/SMAD signalling pathways. Next, we
      tested the effect of Hamp1 deletion, and low iron diets, on M.tb infection. Hamp1
      knockout mice did not have a significantly altered M.tb mycobacterial load in
      either the lungs or spleen. Up to 10 weeks of dietary iron restriction did not
      robustly affect disease outcome despite causing iron deficiency anaemia. Taken
      together, our data indicate that unlike with many other infections, hepcidin is
      decreased following M.tb infection, and show that hepcidin ablation does not
      influence M.tb growth in vivo. Furthermore, because even severe iron deficiency
      did not affect M.tb mycobacterial load, we suggest that the mechanisms M.tb uses
      to scavenge iron from the host must be extremely efficient, and may therefore
      represent potential targets for drugs and vaccines.

PMID- 29324802
TI  - Prognostic value of liver stiffness measurement for the liver-related surgical
      outcomes of patients under hepatic resection: A meta-analysis.
AB  - BACKGROUND: Previous studies have discussed the liver stiffness measurement (LSM)
      performance on predicting liver-related surgical outcomes for patients of
      hepatocellular carcinoma (HCC) under hepatic resection, yet there is much
      variation in reporting and consistency of findings. Therefore, we report a meta
      analysis on this issue. METHODS: We comprehensively searched PubMed, Embase, and
      Web of science to find the eligible cohort studies. The pooled Odds Ratios (OR)
      and 95% confidence intervals (CIs) were calculated to evaluate effect. The
      weighted mean LSM value was calculated as the optimal LSM cut-off value among
      studies. RESULTS: 12 prospective cohort studies and one retrospective cohort
      study, including a total of 1942 cases were identified. The pooled results showed
      that preoperative LSM is significantly associated with the occurrence of overall
      postoperative complications (OR 1.76, 95% CI 1.46-2.11). In addition, a weighted
      mean LSM value of 14.2 kPa and 11.3KPa were suggested as the optimal LSM cut-off
      value reference using transient elastoqraphy (TE) for predicting overall
      postoperative complications in Asia countries and European countries,
      respectively. CONCLUSIONS: Preoperative LSM should be taken into account
      cautiously in the management of patients undergoing hepatectomy of HCC. Future
      studies could focus on setting a prognostic model integrated with LSM in
      predicting post-hepatectomy outcomes.

PMID- 29324803
TI  - Genetic dissection of the relationships between grain yield components by genome
      wide association mapping in a collection of tetraploid wheats.
AB  - Increasing grain yield potential in wheat has been a major target of most
      breeding programs. Genetic advance has been frequently hindered by negative
      correlations among yield components that have been often observed in segregant
      populations and germplasm collections. A tetraploid wheat collection was
      evaluated in seven environments and genotyped with a 90K SNP assay to identify
      major and stable quantitative trait loci (QTL) for grain yield per spike (GYS),
      kernel number per spike (KNS) and thousand-kernel weight (TKW), and to analyse
      the genetic relationships between the yield components at QTL level. The genome
      wide association analysis detected eight, eleven and ten QTL for KNS, TKW and
      GYS, respectively, significant in at least three environments or two environments
      and the mean across environments. Most of the QTL for TKW and KNS were found
      located in different marker intervals, indicating that they are genetically
      controlled independently by each other. Out of eight KNS QTL, three were
      associated to significant increases of GYS, while the increased grain number of
      five additional QTL was completely or partially compensated by decreases in grain
      weight, thus producing no or reduced effects on GYS. Similarly, four consistent
      and five suggestive TKW QTL resulted in visible increase of GYS, while seven
      additional QTL were associated to reduced effects in grain number and no effects
      on GYS. Our results showed that QTL analysis for detecting TKW or KNS alleles
      useful for improving grain yield potential should consider the pleiotropic
      effects of the QTL or the association to other QTLs.

PMID- 29324804
TI  - Genome-wide identification, characterization and expression profile analysis of
      expansins gene family in sugarcane (Saccharum spp.).
AB  - Expansins refer to a family of closely related non-enzymatic proteins found in
      the plant cell wall that are involved in the cell wall loosening. In addition,
      expansins appear to be involved in different physiological and environmental
      responses in plants such as leaf and stem initiation and growth, stomata opening
      and closing, reproduction, ripening and stress tolerance. Sugarcane (Saccharum
      spp.) is one of the main crops grown worldwide. Lignocellulosic biomass from
      sugarcane is one of the most promising raw materials for the ethanol industry.
      However, the efficient use of lignocellulosic biomass requires the optimization
      of several steps, including the access of some enzymes to the hemicellulosic
      matrix. The addition of expansins in an enzymatic cocktail or their genetic
      manipulation could drastically improve the saccharification process of feedstock
      biomass by weakening the hydrogen bonds between polysaccharides present in plant
      cell walls. In this study, the expansin gene family in sugarcane was identified
      and characterized by in silico analysis. Ninety two putative expansins in
      sugarcane (SacEXPs) were categorized in three subfamilies after phylogenetic
      analysis. The expression profile of some expansin genes in leaves of sugarcane in
      different developmental stages was also investigated. This study intended to
      provide suitable expansin targets for genetic manipulation of sugarcane aiming at
      biomass and yield improvement.

PMID- 29324805
TI  - Intranasal vaccination with M2e5x virus-like particles induces humoral and
      cellular immune responses conferring cross-protection against heterosubtypic
      influenza viruses.
AB  - Current influenza vaccines do not provide broad cross-protection. Here, we report
      that intranasal vaccination with virus-like particles containing the highly
      conserved multiple ectodomains of matrix protein 2 (M2e5x VLP) of influenza virus
      induces broad cross-protection by M2-specific humoral and cellular immune
      responses. M2e5x VLP intranasal vaccination prevented severe weight loss,
      attenuated inflammatory cytokines and cellular infiltrates, and lowered viral
      loads, and induced germinal center phenotypic B and plasma cells. In addition,
      depletion studies demonstrate the protective roles of CD4 and CD8 T cells induced
      by M2e5x VLP intranasal vaccination. Thus, this study provides evidence that
      mucosal delivery of M2e5x VLP vaccine provides cross-protection by inducing
      humoral and cellular immune responses.

PMID- 29324806
TI  - Immunocompetent host develops mild intestinal inflammation in acute infection
      with Toxoplasma gondii.
AB  - Toxoplasma gondii (T. gondii) is the causative agent of toxoplasmosis, common
      zoonosis among vertebrates and high incidence worldwide. During the infection,
      the parasite needs to transpose the intestinal barrier to spread throughout the
      body, which may be a trigger for an inflammatory reaction. This work evaluated
      the inflammatory alterations of early T. gondii infection in peripheral blood
      cells, in the mesenteric microcirculation, and small intestinal tissue by
      measurement of MPO (myeloperoxidase) activity and NO (nitric oxide) level in
      rats. Animals were randomly assigned into control group (CG) that received saline
      orally and groups infected with 5,000 oocysts for 6 (G6), 12 (G12), 24 (G24), 48
      (G48) and 72 hours (G72). Blood samples were collected for total and differential
      leukocyte count. Intravital microscopy was performed in the mesentery to evaluate
      rolling and adhesion of leukocytes. After euthanasia, 0.5cm of the duodenum,
      jejunum and ileum were collected for the determination of MPO activity, NO level
      and PCR to identify the parasite DNA and also the mesentery were collected to
      perform immunohistochemistry on frozen sections to quantify adhesion molecules
      ICAM-1, PECAM-1 and P-Selectin. The parasite DNA was identified in all infected
      groups and there was an increase in leukocytes in the peripheral blood and in
      expression of ICAM-1 and PECAM-1 in G6 and G12, however, the expression of P
      selectin was reduced in G12. Leukocytes are in rolling process during the first
      12 hours and they are adhered at 24 hours post-infection. The activity of MPO
      increased in the duodenum at 12 hours, and NO increased in the jejunum in G72 and
      ileum in G24, G48 and G72. Our study demonstrated that T. gondii initiates the
      infection precociously (at 6 hours) leading to a systemic activation of innate
      immune response resulting in mild inflammation in a less susceptible experimental
      model.

PMID- 29324807
TI  - VEGF may contribute to macrophage recruitment and M2 polarization in the decidua.
AB  - It is increasingly evident that cytokines and growth factors produced in the
      decidua play a pivotal role in the regulation of the local immune
      microenvironment and the establishment of pregnancy. One of the major growth
      factors produced in the decidua is vascular endothelial growth factor (VEGF),
      which acts not only on endothelial cells, but also on multiple other cell types,
      including macrophages. We sought to determine whether decidua-derived VEGF
      affects macrophage recruitment and polarization using human endometrial/decidual
      tissue samples, primary human endometrial stromal cells (ESCs), and the human
      monocyte cell line THP1. In situ hybridization was used for assessment of local
      VEGF expression and immunohistochemistry was used for identification and
      localization of CD68-positive endometrial macrophages. Macrophage migration in
      culture was assessed using a transwell migration assay, and the various M1/M2
      phenotypic markers and VEGF expression were assessed using quantitative real-time
      PCR (qRT-PCR). We found dramatic increases in both VEGF levels and macrophage
      numbers in the decidua during early pregnancy compared to the secretory phase
      endometrium (non-pregnant), with a significant increase in M2 macrophage markers,
      suggesting that M2 is the predominant macrophage phenotype in the decidua.
      However, decidual samples from preeclamptic pregnancies showed a significant
      shift in macrophage phenotype markers, with upregulation of M1 and downregulation
      of M2 markers. In THP1 cultures, VEGF treatment significantly enhanced macrophage
      migration and induced M1 macrophages to shift to an M2 phenotype. Moreover,
      treatment with conditioned media from decidualized ESCs induced changes in
      macrophage migration and polarization similar to that of VEGF treatment. These
      effects were abrogated by the addition of a potent VEGF inhibitor. Together these
      results suggest that decidual VEGF plays a significant role in macrophage
      recruitment and M2 polarization, and that inhibition of VEGF signaling may
      contribute to the shift in macrophage polarity observed in different pregnancy
      disorders, including preeclampsia.

PMID- 29324809
TI  - Temporal trends in arthropod abundances after the transition to organic farming
      in paddy fields.
AB  - Organic farming aims to reduce the effect on the ecosystem and enhance
      biodiversity in agricultural areas, but the long-term effectiveness of its
      application is unclear. Assessments have rarely included various taxonomic groups
      with different ecological and economic roles. In paddy fields with different
      numbers of years elapsed since the transition from conventional to organic
      farming, we investigated changes in the abundance of insect pests, generalist
      predators, and species of conservation concern. The abundance of various
      arthropods exhibited diverse trends with respect to years elapsed since the
      transition to organic farming. Larval lepidopterans, Tetragnatha spiders, and
      some planthoppers and stink bugs showed non-linear increases over time,
      eventually reaching saturation, such as the abundance increasing for several
      years and then becoming stable after 10 years. This pattern can be explained by
      the effects of residual pesticides, the lag time of soil mineralization, and
      dispersal limitation. A damselfly (Ischnura asiatica) did not show a particular
      trend over time, probably due to its rapid immigration from source habitats.
      Unexpectedly, both planthoppers and some leafhoppers exhibited gradual decreases
      over time. As their abundances were negatively related to the abundance of
      Tetragnatha spiders, increased predation by natural enemies might gradually
      decrease these insect populations. These results suggest that the consideration
      of time-dependent responses of organisms is essential for the evaluation of the
      costs and benefits of organic farming, and such evaluations could provide a basis
      for guidelines regarding the length of time for organic farming to restore
      biodiversity or the economic subsidy needed to compensate for pest damage.

PMID- 29324808
TI  - A novel prescription pedometer-assisted walking intervention and weight
      management for Chinese occupational population.
AB  - BACKGROUND AND AIM: Information technology has been previously used for the
      research and practice of health promotion. Appropriate and effective health
      promotion methods used by professional groups remain to be investigated. This
      study aimed to assess the feasibility and effectiveness of a weight management
      program among the Chinese occupational population using and a novel information
      technology exercise prescription. STUDY DESIGN AND PARTICIPANTS: A 3-month open,
      self-monitored intervention trial, involving individualized pedometer-assisted
      exercise prescription and a one-time targeted dietary guidance prior to exercise
      was conducted on the Chinese occupational population aged 18-65 years in China
      from 2015 to 2016. Data were collected from March 2015 to May 2016 and analyzed
      from June 2016 to August 2016. Participants were also asked to synchronize
      exercise data of the pedometer to the Internet-based Health System Center daily
      (at least weekly), by connecting to the personal computer (PC) using a USB cable
      or via Bluetooth. RESULTS: Eligible participants included 802 Chinese
      occupational persons, and 718 of them followed exercise interventions with 89.5%
      (718/802) adherence to the exercise programs. Of them, 688 participants completed
      the program with 85.8% (688/802) adherence to the exercise program and their data
      were analyzed. Weight decreased by 2.2% among all overweight/obese participants,
      with 1.8% reduction in waist circumference and 3.3% reduction in body fat
      percentage (p< 0.001). Weight and body fat percentage in normal-weight
      individuals decreased by 0.7% and 2.5%, respectively (p < 0.01). A weight gain of
      1.0% was observed in all underweight participants (p< 0.05), and 68.2% (208/305)
      of overweight/obese participants experienced weight loss, with an average
      reduction of 3.5%, with 20.2% (42/208) of them achieving weight loss >=5%. Blood
      pressure and fasting serum glucose decreased significantly in both the
      overweight/obese and the normal-weight individuals (p < 0.05). The incidence of
      hypertension was significantly lower and lifestyle behavior significantly
      improved (p < 0.05). CONCLUSION: The prescription pedometer-assisted walking
      intervention can effectively improve exercise adherence and manage weight. This
      approach was also effective in controlling the risk factors of weight-related
      chronic diseases. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR)
      ChiCTR-OOh-16010229.

PMID- 29324810
TI  - Course of SP-D, YKL-40, CCL18 and CA 15-3 in adult patients hospitalised with
      community-acquired pneumonia and their association with disease severity and
      aetiology: A post-hoc analysis.
AB  - BACKGROUND AND AIM: SP-D, YKL-40, CCL18 and CA 15-3 are pulmonary markers that
      have been extensively investigated in different chronic pulmonary diseases.
      However, in acute pulmonary diseases, such as community-acquired pneumonia (CAP),
      little is known about the course of these markers and their relationship with the
      aetiological agent. The aim of this study was to investigate the course of these
      four markers in CAP and to study influence of disease severity, aetiology and
      antibiotic use prior to admission on their course. METHODS: We included 291 adult
      patients hospitalised with CAP and 20 healthy controls. Measurements were
      performed in serum of day 0, 2, and 4, and at least 30 days after admission.
      RESULTS: Our most important results were: 1) At all time-points, including 30
      days after admission, YKL-40 and CCL18 levels were higher in CAP patients
      compared to healthy controls; and 2) Patients with CAP caused by an
      intracellular, atypical bacterium had lower YKL-40 and especially CCL18 levels on
      and during admission in comparison with other or unknown CAP aetiology.
      CONCLUSIONS: Our findings suggest that these pulmonary markers could be useful to
      assess CAP severity and, especially YKL-40 and CCL18 by helping predict CAP
      caused by atypical pathogens.

PMID- 29324811
TI  - Scale-up of Kenya's national HIV viral load program: Findings and lessons
      learned.
AB  - OBJECTIVES: Kenya is one of the first African countries to scale up a national
      HIV viral load monitoring program. We sought to assess program scale up using the
      national database and identify areas for systems strengthening. METHODS: Data
      from January 2012 to March 2016 were extracted from Kenya's national viral load
      database. Characteristics of 1,108,356 tests were assessed over time, including
      reason for testing, turnaround times, test results, treatment regimens, and socio
      demographic information. RESULTS: The number of facilities offering viral load
      testing increased to ~2,000 with >40,000 tests being conducted per month by 2016.
      By March 2016, most (84.2%) tests were conducted for routine monitoring purposes
      and the turnaround time from facility-level sample collection to result dispatch
      from the lab was 21(24) [median (IQR)] days. Although the proportions of repeat
      viral load tests increased over time, the volumes were lower than expected.
      Elevated viral load was much more common in pediatric and adolescent patients (0
      <3 years: 43.1%, 3-<10 years: 34.5%, 10-<20 years: 36.6%) than in adults (30-<60
      years: 13.3%; p<0.001). CONCLUSIONS: Coverage of viral load testing dramatically
      increased in Kenya to >50% of patients on antiretroviral therapy (ART) by early
      2016 and represents a relatively efficient laboratory system. However,
      strengthening of patient tracking mechanisms and viral load result utilization
      may be necessary to further improve the system. Additional focus is needed on
      paediatric/adolescent patients to improve viral suppression in these groups.
      Kenya's national viral load database has demonstrated its usefulness in assessing
      laboratory programs, tracking trends in patient characteristics, monitoring scale
      up of new policies and programs, and identifying problem areas for further
      investigation.

PMID- 29324812
TI  - Identifying unmet clinical need in hypertrophic cardiomyopathy using national
      electronic health records.
AB  - INTRODUCTION: To evaluate unmet clinical need in unselected hypertrophic
      cardiomyopathy (HCM) patients to determine the risk of a wide range of subsequent
      cardiovascular disease endpoints and safety endpoints relevant for trial design.
      METHODS: Population based cohort (CALIBER, linked primary care, hospital and
      mortality records in England, period 1997-2010), all people diagnosed with HCM
      were identified and matched by age, sex and general practice with ten randomly
      selected people without HCM. Random-effects Poisson models were used to assess
      the associations between HCM and cardiovascular diseases and bleeding. RESULTS:
      Among 3,290,455 eligible people a diagnosis of hypertrophic cardiomyopathy was
      found in 4 per 10,000. Forty-one percent of the 1,160 individuals with
      hypertrophic cardiomyopathy were women and the median age was 57 years. The
      median follow-up was 4.0 years. Compared to general population controls, people
      with HCM had higher risk of ventricular arrhythmia (incidence rate ratio = 23.53,
      [95% confidence interval 12.67-43.72]), cardiac arrest or sudden cardiac death
      (6.33 [3.69-10.85]), heart failure (4.31, [3.30-5.62]), and atrial fibrillation
      (3.80 [3.04-4.75]). HCM was also associated with a higher incidence of myocardial
      infarction ([MI] 1.90 [1.27-2.84]) and coronary revascularisation (2.32 [1.46
      3.69]).The absolute Kaplan-Meier risks at 3 years were 8.8% for the composite
      endpoint of cardiovascular death or heart failure, 8.4% for the composite of
      cardiovascular death, stroke or myocardial infarction, and 1.5% for major
      bleeding. CONCLUSIONS: Our study identified major unmet need in HCM and
      highlighted the importance of implementing improved cardiovascular prevention
      strategies to increase life-expectancy of the contemporary HCM population. They
      also show that national electronic health records provide an effective method for
      identifying outcomes and clinically relevant estimates of composite efficacy and
      safety endpoints essential for trial design in rare diseases.

PMID- 29324813
TI  - Increase in extraction of I-123 iomazenil in patients with chronic cerebral
      ischemia.
AB  - BACKGROUND: Cerebral extraction of diffusively distributed substances like oxygen
      has been suggested to change according to the cerebral blood flow (CBF) and
      status of the microvasculature. The relationships between the cerebral extraction
      of diffusively distributed lipophilic tracers and the severity of cerebral
      ischemia has not yet been clarified. In the present study, we attempted to
      elucidate the association between the extraction fraction of the lipophilic
      tracer I-123 iomazenil (IMZ) (IMZ-EF) and the oxygen extraction fraction (OEF)
      derived from O-15 PET in patients with chronic steno-occlusive disease of
      internal carotid artery (ICA) or middle cerebral artery (MCA). METHODS: Seven
      patients with unilateral chronic severe stenosis or occlusion of the middle
      cerebral/internal cerebral artery were prospectively recruited for this study.
      All the patients underwent both O-15 PET and quantitative I-123 IMZ SPECT.
      Parametric images derived from the PET and SPECT scans were anatomically
      normalized and evaluated by automated image analysis based on the volume-of
      interest template. RESULTS: The asymmetry index (AI) of IMZ-EF was shown to be
      significantly correlated with the AI of OEF (r = 0.562, P < 0.001) in the
      internal carotid artery perfusion area. Strong and significant correlation
      between the AI of the influx rate constant K1 of IMZ and the AI of the cerebral
      metabolic rate of oxygen (r = 0.552, P = 0.001) was clarified. CONCLUSIONS: Our
      results suggested that the transportation efficiency of I-123 IMZ into the brain
      tissue was an indicator for evaluating severity of cerebral ischemia in patients
      with chronic steno-occlusive disease of ICA or MCA. Cerebral metabolic state can
      possibly be estimated by I-123 IMZ SPECT without cyclotron.

PMID- 29324814
TI  - Comprehensive molecular profiling of advanced/metastatic olfactory
      neuroblastomas.
AB  - Olfactory neuroblastoma (ONB) is a rare, locally aggressive, malignant neoplasm
      originating in the olfactory epithelium in the nasal vault. The recurrence rate
      of ONB remains high and there are no specific treatment guidelines for
      recurrent/metastatic ONBs. This study retrospectively evaluated 23 ONB samples
      profiled at Caris Life Sciences (Phoenix, Arizona) using DNA sequencing
      (Sanger/NGS [Illumina], n = 15) and gene fusions (Archer FusionPlex, n = 6),
      whole genome RNA microarray (HumanHT-12 v4 beadChip, Illumina, n = 4), gene copy
      number assays (chromogenic and fluorescent in situ hybridization), and
      immunohistochemistry. Mutations were detected in 63% ONBs including TP53, CTNNB1,
      EGFR, APC, cKIT, cMET, PDGFRA, CDH1, FH, and SMAD4 genes. Twenty-one genes were
      over-expressed and 19 genes under-expressed by microarray assay. Some of the
      upregulated genes included CD24, SCG2, and IGFBP-2. None of the cases harbored
      copy number variations of EGFR, HER2 and cMET genes, and no gene fusions were
      identified. Multiple protein biomarkers of potential response or resistance to
      classic chemotherapy drugs were identified, such as low ERCC1 [cisplatin
      sensitivity in 10/12], high TOPO1 [irinotecan sensitivity in 12/19], high TUBB3
      [vincristine resistance in 13/14], and high MRP1 [multidrug resistance in 6/6
      cases]. None of the cases (0/10) were positive for PD-L1 in tumor cells.
      Overexpression of pNTRK was observed in 67% (4/6) of the cases without underlying
      genetic alterations. Molecular alterations detected in our study (e.g., Wnt and
      cKIT/PDGFRA pathways) are potentially treatable using novel therapeutic
      approaches. Identified protein biomarkers of response or resistance to classic
      chemotherapy could be useful in optimizing existing chemotherapy treatment(s) in
      ONBs.

PMID- 29324816
TI  - Changes in respiratory and non-respiratory symptoms in occupants of a large
      office building over a period of moisture damage remediation attempts.
AB  - There is limited information on the natural history of building occupants' health
      in relation to attempts to remediate moisture damage. We examined changes in
      respiratory and non-respiratory symptoms in 1,175 office building occupants over
      seven years with multiple remediation attempts. During each of four surveys, we
      categorized participants using a severity score: 0 = asymptomatic; 1 = mild,
      symptomatic in the last 12 months, but not frequently in the last 4 weeks; 2 =
      severe, symptomatic at least once weekly in the last 4 weeks. Building-related
      symptoms were defined as improving away from the building. We used random
      intercept models adjusted for demographics, smoking, building tenure, and
      microbial exposures to estimate temporal changes in the odds of building-related
      symptoms or severity scores independent of the effect of microbial exposures.
      Trend analyses of combined mild/severe symptoms showed no changes in the odds of
      respiratory symptoms but significant improvement in non-respiratory symptoms over
      time. Separate analyses showed increases in the odds of severe respiratory
      symptoms (odds ratio/year = 1.15-1.16, p-values<0.05) and severity scores
      (0.02/year, p-values<0.05) for wheezing and shortness of breath on exertion, due
      to worsening of participants in the mild symptom group. For non-respiratory
      symptoms, we found no changes in the odds of severe symptoms but improvement in
      severity scores (-0.04--0.01/year, p-values<0.05) and the odds for mild fever and
      chills, excessive fatigue, headache, and throat symptoms (0.65-0.79/year, p
      values<0.05). Our study suggests that after the onset of respiratory and severe
      non-respiratory symptoms associated with dampness/mold, remediation efforts might
      not be effective in improving occupants' health.

PMID- 29324817
TI  - Synthesis, characterization and in vitro antitrypanosomal activities of new
      carboxamides bearing quinoline moiety.
AB  - The reported toxicities of current antitrypanosomal drugs and the emergence of
      drug resistant trypanosomes underscore the need for the development of new
      antitrypanosomal agents. We report herein the synthesis and antitrypanosomal
      activity of 24 new amide derivatives of 3-aminoquinoline, bearing substituted
      benzenesulphonamide. Nine of the new derivatives showed comparable
      antitrypanosomal activities at IC50 range of 1-6 nM (melarsoprol 5 nM). Compound
      11n and 11v are more promising antitrypanosomal agents with IC50 1.0 nM than the
      rest of the reported derivatives. The novel compounds showed satisfactory
      predicted physico-chemical properties including oral bioavailability,
      permeability and transport properties.

PMID- 29324815
TI  - Biophysical insights from a single chain camelid antibody directed against the
      Disrupted-in-Schizophrenia 1 protein.
AB  - Accumulating evidence suggests an important role for the Disrupted-in
      Schizophrenia 1 (DISC1) protein in neurodevelopment and chronic mental illness.
      In particular, the C-terminal 300 amino acids of DISC1 have been found to mediate
      important protein-protein interactions and to harbor functionally important
      phosphorylation sites and disease-associated polymorphisms. However, long
      disordered regions and oligomer-forming subdomains have so far impeded structural
      analysis. VHH domains derived from camelid heavy chain only antibodies are
      minimal antigen binding modules with appreciable solubility and stability, which
      makes them well suited for the stabilizing proteins prior to structural
      investigation. Here, we report on the generation of a VHH domain derived from an
      immunized Lama glama, displaying high affinity for the human DISC1 C region (aa
      691-836), and its characterization by surface plasmon resonance, size exclusion
      chromatography and immunological techniques. The VHH-DISC1 (C region) complex was
      also used for structural investigation by small angle X-ray scattering analysis.
      In combination with molecular modeling, these data support predictions regarding
      the three-dimensional fold of this DISC1 segment as well as its steric
      arrangement in complex with our VHH antibody.

PMID- 29324818
TI  - Root-tip-mediated inhibition of hydrotropism is accompanied with the suppression
      of asymmetric expression of auxin-inducible genes in response to moisture
      gradients in cucumber roots.
AB  - In cucumber seedlings, gravitropism interferes with hydrotropism, which results
      in the nearly complete inhibition of hydrotropism under stationary conditions.
      However, hydrotropic responses are induced when the gravitropic response in the
      root is nullified by clinorotation. Columella cells in the root cap sense
      gravity, which induces the gravitropic response. In this study, we found that
      removing the root tip induced hydrotropism in cucumber roots under stationary
      conditions. The application of auxin transport inhibitors to cucumber seedlings
      under stationary conditions suppressed the hydrotropic response induced by the
      removal of the root tip. To investigate the expression of genes related to
      hydrotropism in de-tipped cucumber roots, we conducted transcriptome analysis of
      gene expression by RNA-Seq using seedlings exhibiting hydrotropic and gravitropic
      responses. Of the 21 and 45 genes asymmetrically expressed during hydrotropic and
      gravitropic responses, respectively, five genes were identical. Gene ontology
      (GO) analysis indicated that the category auxin-inducible genes was significantly
      enriched among genes that were more highly expressed in the concave side of the
      root than the convex side during hydrotropic or gravitropic responses. Reverse
      transcription followed by quantitative polymerase chain reaction (RT-qPCR)
      analysis revealed that root hydrotropism induced under stationary conditions (by
      removing the root tip) was accompanied by the asymmetric expression of several
      auxin-inducible genes. However, intact roots did not exhibit the asymmetric
      expression patterns of auxin-inducible genes under stationary conditions, even in
      the presence of a moisture gradient. These results suggest that the root tip
      inhibits hydrotropism by suppressing the induction of asymmetric auxin
      distribution. Auxin transport and distribution not mediated by the root tip might
      play a role in hydrotropism in cucumber roots.

PMID- 29324819
TI  - Development of the Japanese version of the Visual Discomfort Scale.
AB  - BACKGROUND: Visual stimuli, such as stripes and texts, can induce "visual
      discomfort" including perceptual and somatic symptoms. Individuals reporting high
      levels of visual discomfort might experience migraine headache and may have
      reduced reading efficiency due to visual perceptual difficulties. This study
      aimed to develop and validate the Japanese version of the Visual Discomfort
      Scale, which measures proneness to visual discomfort. METHODS AND RESULTS: In
      Survey 1, 428 adults completed the Japanese version and a questionnaire assessing
      migraine morbidity. Rasch analysis revealed that the Japanese version is a
      unidimensional scale with a high amount of unexplained variance due to random
      noise rather than another dimension, and has high person and item reliabilities.
      Participants with migraine exhibited high scores in the Japanese version,
      indicating the construct validity of the scale. Survey 2 with 118 adults revealed
      a strong test-retest correlation for the Japanese version, indicating the
      stability of the scale. CONCLUSION: The Japanese version of the Visual Discomfort
      Scale is a sufficiently reliable and valid scale for assessing visual discomfort,
      although its unidimensionality leaves room for further improvements.

PMID- 29324820
TI  - Incidence and prevalence of patellofemoral pain: A systematic review and meta
      analysis.
AB  - BACKGROUND: Patellofemoral pain is considered one of the most common forms of
      knee pain, affecting adults, adolescents, and physically active populations.
      Inconsistencies in reported incidence and prevalence exist and in relation to the
      allocation of healthcare and research funding, there is a clear need to
      accurately understand the epidemiology of patellofemoral pain. METHODS: An
      electronic database search was conducted, as well as grey literature databases,
      from inception to June 2017. Two authors independently selected studies,
      extracted data and appraised methodological quality. If heterogeneous, data were
      analysed descriptively. Where studies were homogeneous, data were pooled through
      a meta-analysis. RESULTS: 23 studies were included. Annual prevalence for
      patellofemoral pain in the general population was reported as 22.7%, and
      adolescents as 28.9%. Incidence rates in military recruits ranged from 9.7
      571.4/1,000 person-years, amateur runners in the general population at
      1080.5/1,000 person-years and adolescents amateur athletes 5.1%-14.9% over 1
      season. One study reported point prevalence within military populations as 13.5%.
      The pooled estimate for point prevalence in adolescents was 7.2% (95% Confidence
      Interval: 6.3%-8.3%), and in female only adolescent athletes was 22.7% (95%
      Confidence Interval 17.4%-28.0%). CONCLUSION: This review demonstrates high
      incidence and prevalence levels for patellofemoral pain. Within the context of
      this, and poor long term prognosis and high disability levels, PFP should be an
      urgent research priority. PROSPERO REGISTRATION: CRD42016038870.

PMID- 29324821
TI  - Slightly increased BMI at young age is a risk factor for future hypertension in
      Japanese men.
AB  - BACKGROUND: Hypertension is developed easily in Asian adults with normal body
      mass index (BMI) (~23 kg/m2), compared with other ethnicities with similar BMI.
      This study tested the hypothesis that slightly increased BMI at young age is a
      risk factor for future hypertension in Japanese men by historical cohort study.
      METHODS: The study participants were 636 male alumni of the physical education
      school. They had available data on their physical examination at college age and
      follow-up investigation between 2007 and 2011. The participants were categorized
      into six categories: BMI at college age of <20.0 kg/m2, 20.0-21.0kg/m2, 21.0
      22.0kg/m2, 22.0-23.0kg/m2, 23.0-24.0kg/m2, and >=24.0kg/m2, and the incidence of
      hypertension was compared. RESULTS: This study covered 27-year follow-up period
      (interquartile range: IQR: 23-31) which included 17,059 person-years of
      observation. Subjects were 22 (22-22) years old at graduated college, and 49 (45
      53) years old at first follow-up investigation. During the period, 120 men
      developed hypertension. The prevalence rates of hypertension for lowest to
      highest BMI categories were 9.4%, 14.6%, 16.1%, 17.5%, 30.3%, and 29.3%,
      respectively (p<0.001 for trend), and their hazard ratios were 1.00 (reference),
      1.80 (95%CI: 0.65-4.94), 2.17 (0.83-5.64), 2.29 (0.89-5.92), 3.60 (1.37-9.47) and
      4.72 (1.78-12.48), respectively (p<0.001 for trend). This trend was similar after
      adjustment for age, year of graduation, smoking, current exercise status and
      current dietary intake. CONCLUSION: Slightly increased BMI at young age is a risk
      factor for future hypertension in Japanese men.

PMID- 29324822
TI  - Biting mechanics and niche separation in a specialized clade of primate seed
      predators.
AB  - We analyzed feeding biomechanics in pitheciine monkeys (Pithecia, Chiropotes,
      Cacajao), a clade that specializes on hard-husked unripe fruit (sclerocarpy) and
      resistant seeds (seed predation). We tested the hypothesis that pitheciine crania
      are well-suited to generate and withstand forceful canine and molar biting, with
      the prediction that they generate bite forces more efficiently and better resist
      masticatory strains than the closely-related Callicebus, which does not
      specialize on unripe fruits and/or seeds. We also tested the hypothesis that
      Callicebus-Pithecia-Chiropotes-Cacajao represent a morphocline of increasing
      sclerocarpic specialization with respect to biting leverage and craniofacial
      strength, consistent with anterior dental morphology. We found that pitheciines
      have higher biting leverage than Callicebus and are generally more resistant to
      masticatory strain. However, Cacajao was found to experience high strain
      magnitudes in some facial regions. We therefore found limited support for the
      morphocline hypothesis, at least with respect to the mechanical performance
      metrics examined here. Biting leverage in Cacajao was nearly identical (or
      slightly less than) in Chiropotes and strain magnitudes during canine biting were
      more likely to follow a Cacajao-Chiropotes-Pithecia trend of increasing strength,
      in contrast to the proposed morphocline. These results could indicate that bite
      force efficiency and derived anterior teeth were selected for in pitheciines at
      the expense of increased strain magnitudes. However, our results for Cacajao
      potentially reflect reduced feeding competition offered by allopatry with other
      pitheciines, which allows Cacajao species to choose from a wider variety of
      fruits at various stages of ripeness, leading to reduction in the selection for
      robust facial features. We also found that feeding biomechanics in sympatric
      Pithecia and Chiropotes are consistent with data on food structural properties
      and observations of dietary niche separation, with the former being well-suited
      for the regular molar crushing of hard seeds and the latter better adapted for
      breaching hard fruits.

PMID- 29324823
TI  - The relationship between personalities and self-report positive driving behavior
      in a Chinese sample.
AB  - Driving behaviors play an important role in accident involvement. Concretely
      speaking, aberrant driving behaviors would cause more accidents, and oppositely
      positive driving behaviors would promote to build safety traffic environment. The
      main goals of this study were to explore the positive driving behavior and its
      relationship with personality in a Chinese sample. A total of 421 licensed
      drivers (286 male and 135 female) from Beijing, China completed the Positive
      Driver Behavior Scale (PDBS), the Driver Behavior Questionnaire (DBQ), the Dula
      Dangerous Driving Index (DDDI) and the Big Five Inventory (BFI) on a voluntary
      and anonymous basis. The results showed that the Chinese version of the PDBS has
      both reliability and validity and that the PDBS was significantly correlated with
      the BFI. Specifically, the PDBS was negatively correlated with neuroticism (r = 
      0.38) and positively correlated with extraversion, agreeableness,
      conscientiousness and openness to experience (the correlation coefficient ranged
      from 0.36 to 0.55). In contrast with previous research, age was negatively
      correlated with the PDBS (r = -0.38) in our sample, which may have resulted from
      less driving experience or a lack of available cognitive resources.

PMID- 29324824
TI  - Assessing the links among environmental contaminants, endocrinology, and
      parasites to understand amphibian declines in montane regions of Costa Rica.
AB  - Amphibians inhabiting montane riparian zones in the Neotropics are particularly
      vulnerable to decline, but the reasons are poorly understood. Because
      environmental contaminants, endocrine disruption, and pathogens often figure
      prominently in amphibian declines it is imperative that we understand how these
      factors are potentially interrelated to affect montane populations. One
      possibility is that increased precipitation associated with global warming
      promotes the deposition of contaminants in montane regions. Increased exposure to
      contaminants, in turn, potentially elicits chronic elevations in circulating
      stress hormones that could contribute to montane population declines by
      compromising resistance to pathogens and/or production of sex steroids regulating
      reproduction. Here, we test this hypothesis by examining contaminant levels,
      stress and sex steroid levels, and nematode abundances in male drab treefrogs,
      Smilisca sordida, from lowland and montane populations in Costa Rica. We found no
      evidence that montane populations were more likely to possess contaminants (i.e.,
      organochlorine, organophosphate and carbamate pesticides or benzidine and
      chlorophenoxy herbicides) than lowland populations. We also found no evidence of
      elevational differences in circulating levels of the stress hormone
      corticosterone, estradiol or progesterone. However, montane populations possessed
      lower androgen levels, hosted more nematode species, and had higher nematode
      abundances than lowland populations. Although these results suggested that
      nematodes contributed to lower androgens in montane populations, we were unable
      to detect a significant inverse relationship between nematode abundance and
      androgen level. Our results suggest that montane populations of this species are
      not at greater risk of exposure to contaminants or chronic stress, but implicate
      nematodes and compromised sex steroid levels as potential threats to montane
      populations.

PMID- 29324825
TI  - Early- and later-phases satellite cell responses and myonuclear content with
      resistance training in young men.
AB  - Satellite cells (SC) are associated with skeletal muscle remodelling after muscle
      damage and/or extensive hypertrophy resulting from resistance training (RT). We
      recently reported that early increases in muscle protein synthesis (MPS) during
      RT appear to be directed toward muscle damage repair, but MPS contributes to
      hypertrophy with progressive muscle damage attenuation. However, modulations in
      acute-chronic SC content with RT during the initial (1st-wk: high damage), early
      (3rd-wk: attenuated damage), and later (10th-wk: no damage) stages is not well
      characterized. Ten young men (27 +/- 1 y, 23.6 +/- 1.0 kg.m-2) underwent 10-wks
      of RT and muscle biopsies (vastus-lateralis) were taken before (Pre) and post
      (48h) the 1st (T1), 5th (T2) and final (T3) RT sessions to evaluate fibre type
      specific SC content, cross-sectional area (fCSA) and myonuclear number by
      immunohistochemistry. We observed RT-induced hypertrophy after 10-wks of RT (fCSA
      increased ~16% in type II, P < 0.04; ~8% in type I [ns]). SC content increased
      48h post-exercise at T1 (~69% in type I [P = 0.014]; ~42% in type II [ns]), and
      this increase was sustained throughout RT (pre T2: ~65%, ~92%; pre T3: ~30% [ns],
      ~87%, for the increase in type I and II, respectively, vs. pre T1 [P < 0.05]).
      Increased SC content was not coupled with changes in myonuclear number. SC have a
      more pronounced role in muscle repair during the initial phase of RT than muscle
      hypertrophy resulted from 10-wks RT in young men. Chronic elevated SC pool size
      with RT is important providing proper environment for future stresses or larger
      fCSA increases.

PMID- 29324826
TI  - Facial responsiveness of psychopaths to the emotional expressions of others.
AB  - Psychopathic individuals show selfish, manipulative, and antisocial behavior in
      addition to emotional detachment and reduced empathy. Their empathic deficits are
      thought to be associated with a reduced responsiveness to emotional stimuli.
      Immediate facial muscle responses to the emotional expressions of others reflect
      the expressive part of emotional responsiveness and are positively related to
      trait empathy. Empirical evidence for reduced facial muscle responses in adult
      psychopathic individuals to the emotional expressions of others is rare. In the
      present study, 261 male criminal offenders and non-offenders categorized
      dynamically presented facial emotion expressions (angry, happy, sad, and neutral)
      during facial electromyography recording of their corrugator muscle activity. We
      replicated a measurement model of facial muscle activity, which controls for
      general facial responsiveness to face stimuli, and modeled three correlated
      emotion-specific factors (i.e., anger, happiness, and sadness) representing
      emotion specific activity. In a multi-group confirmatory factor analysis, we
      compared the means of the anger, happiness, and sadness latent factors between
      three groups: 1) non-offenders, 2) low, and 3) high psychopathic offenders. There
      were no significant mean differences between groups. Our results challenge
      current theories that focus on deficits in emotional responsiveness as leading to
      the development of psychopathy and encourage further theoretical development on
      deviant emotional processes in psychopathic individuals.

PMID- 29324827
TI  - Psychometric properties of the Arabic version of the 12-item diabetes fatalism
      scale.
AB  - BACKGROUND: There are widespread fatalistic beliefs in Arab countries, especially
      among individuals with diabetes. However, there is no tool to assess diabetes
      fatalism in this population. This study describes the processes used to create an
      Arabic version of the Diabetes Fatalism Scale (DFS) and examine its psychometric
      properties. METHODS: A descriptive correlational design was used with a
      convenience sample of Lebanese adults (N = 274) with type 2 diabetes recruited
      from a major hospital in Beirut, Lebanon and by snowball sampling. The 12- item
      Diabetes Fatalism Scale- Arabic (12-item DFS-Ar) was back-translated from the
      original version, pilot tested on 22 adults with type 2 diabetes and then
      administered to 274 patients to assess the validity and reliability of the scale.
      Confirmatory factor analysis (CFA) was used to test the hypothesized factor
      structure. Cronbach's alpha was used to test for reliability. RESULTS: CFA
      supported the existence of the three factor hypothesis of the original DFS scale.
      The five items measuring "emotional distress" loaded under Factor 1, the four
      items measuring "spiritual coping" loaded under factor 2 and the last three items
      measuring "perceived self-efficacy" of the original scale loaded under Factor 3
      (p <0.001 for all three subscales). Goodness of fit indices confirmed
      adequateness of the CFA model (CFI = 0.97, TLI = 0.96, RMSEA = 0.067 and pclose =
      0.05). The 12-item DFS-Ar showed good reliability (Cronbach's alpha of 0.86) and
      significantly predicted HbA1c (beta = 0.20, p < 0.01). After adjusting for the
      demographic characteristics and the number of diabetes comorbid conditions, the
      12-item DFS-Ar score was independently associated with HbA1c in a multivariable
      model (beta = 0.16, p < 0.05). CONCLUSIONS: The 12-item DFS-Ar demonstrated good
      psychometric properties that are comparable to the original scale. It is a valid
      and reliable measure of diabetes fatalism. Further testing with larger and non
      Lebanese Arabic population is needed.

PMID- 29324828
TI  - Correction: Economic evaluation of the one-hour rule-out and rule-in algorithm
      for acute myocardial infarction using the high-sensitivity cardiac troponin T
      assay in the emergency department.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0187662.].

PMID- 29324829
TI  - Electrode placement on the forearm for selective stimulation of finger
      extension/flexion.
AB  - It is still challenging to achieve a complex grasp or fine finger control by
      using surface functional electrical stimulation (FES), which usually requires a
      precise electrode configuration under laboratory or clinical settings. The goals
      of this study are as follows: 1) to study the possibility of selectively
      activating individual fingers; 2) to investigate whether the current activation
      threshold and selective range of individual fingers are affected by two factors:
      changes in the electrode position and forearm rotation (pronation, neutral and
      supination); and 3) to explore a theoretical model for guidance of the electrode
      placement used for selective activation of individual fingers. A coordinate
      system with more than 400 grid points was established over the forearm skin
      surface. A searching procedure was used to traverse all grid points to identify
      the stimulation points for finger extension/flexion by applying monophasic
      stimulation pulses. Some of the stimulation points for finger extension and
      flexion were selected and tested in their respective two different forearm
      postures according to the number and the type of the activated fingers and the
      strength of finger action response to the electrical stimulation at the
      stimulation point. The activation thresholds and current ranges of the
      selectively activated finger at each stimulation point were determined by visual
      analysis. The stimulation points were divided into three groups ("Low", "Medium"
      and "High") according to the thresholds of the 1st activated fingers. The angles
      produced by the selectively activated finger within selective current ranges were
      measured and analyzed. Selective stimulation of extension/flexion is possible for
      most fingers. Small changes in electrode position and forearm rotation have no
      significant effect on the threshold amplitude and the current range for the
      selective activation of most fingers (p > 0.05). The current range is the largest
      (more than 2 mA) for selective activation of the thumb, followed by those for the
      index, ring, middle and little fingers. The stimulation points in the "Low" group
      for all five fingers lead to noticeable finger angles at low current intensity,
      especially for the index, middle, and ring fingers. The slopes of the finger
      angle variation in the "Low" group for digits 2~4 are inversely proportional to
      the current intensity, whereas the slopes of the finger angle variation in other
      groups and in all groups for the thumb and little finger are proportional to the
      current intensity. It is possible to selectively activate the extension/flexion
      of most fingers by stimulating the forearm muscles. The physiological
      characteristics of each finger should be considered when placing the negative
      electrode for selective stimulation of individual fingers. The electrode
      placement used for the selective activation of individual fingers should not be
      confined to the location with the lowest activation threshold.

PMID- 29324830
TI  - Nano-Pulse Stimulation induces immunogenic cell death in human papillomavirus
      transformed tumors and initiates an adaptive immune response.
AB  - Nano-Pulse Stimulation (NPS) is a non-thermal pulsed electric field modality that
      has been shown to have cancer therapeutic effects. Here we applied NPS treatment
      to the human papillomavirus type 16 (HPV 16)-transformed C3.43 mouse tumor cell
      model and showed that it is effective at eliminating primary tumors through the
      induction of immunogenic cell death while subsequently increasing the number of
      tumor-infiltrating lymphocytes within the tumor microenvironment. In vitro NPS
      treatment of C3.43 cells resulted in a doubling of activated caspase 3/7 along
      with the translocation of phosphatidylserine (PS) to the outer leaflet of the
      plasma membrane, indicating programmed cell death activity. Tumor-bearing mice
      receiving standard NPS treatment showed an initial decrease in tumor volume
      followed by clearing of tumors in most mice, and a significant increase in
      overall survival. Intra-tumor analysis of mice that were unable to clear tumors
      showed an inverse correlation between the number of tumor infiltrating
      lymphocytes and the size of the tumor. Approximately half of the mice that
      cleared established tumors were protected against tumor re-challenge on the
      opposite flank. Selective depletion of CD8+ T cells eliminated this protection,
      suggesting that NPS treatment induces an adaptive immune response generating CD8+
      T cells that recognize tumor antigen(s) associated with the C3.43 tumor model.
      This method may be utilized in the future to not only ablate primary tumors, but
      also to induce an anti-tumor response driven by effector CD8+ T cells capable of
      protecting individuals from disease recurrence.

PMID- 29324831
TI  - The PlantLIBRA consumer survey: Findings on the use of plant food supplements in
      Italy.
AB  - BACKGROUND: Food supplements, and in particular those containing botanicals
      (plant food supplements, PFS), have in recent decades been of great interest both
      to consumers and to food/pharmaceutical industries. OBJECTIVES: The aim of this
      paper is to examine replies by Italian consumers to the PlantLIBRA consumers'
      survey in order to: 1) assess the behaviour of an Italian population with respect
      to the use of PFS, and to compare it with that of other 5 countries involved in
      the whole survey; 2) identify different habits in the 4 Italian cities selected
      according to their geographical distribution; 3) collect independent information
      on the actual intake of PFS and consumers' behaviour. SUBJECTS/SETTING: 397
      Italian consumers enrolled, 187 males (49.5%) and 191 female (50.5%). The
      distribution of subjects among the 4 cities included was: Milan 99; Venice 90;
      Rome 96 and Catania 96. RESULTS: The interest in PFS in Italy is high, the
      prevalence of "regular" consumers being 22.7%. Some differences were observed
      between the 4 cities involved: the pattern of use during the year was specific to
      each city; consumers in Milan reported reasons to use PFS significantly different
      from those in the whole Italian sample and did not indicate supermarkets as an
      important place of purchase; respondents from Rome and Catania more frequently
      used family doctors and pharmacists as a source of recommendation. Some
      significant difference among cities, sex and age groups were observed when the
      most frequently used botanicals were ranked. CONCLUSIONS: The results provide new
      insights on the socio-economic characteristics and lifestyle of Italian PFS
      consumers, on their reasons for and pattern of use, and on their behaviour and
      expectations. The value of this information is not restricted to the specific
      country (Italy) but allows for a more general evaluation of the pattern of use,
      according to habits and geographical area.

PMID- 29324832
TI  - Differential microRNA expression in breast cancer with different onset age.
AB  - PURPOSE: The lower breast cancer incidence in Asian populations compared with
      Western populations has been speculated to be caused by environmental and genetic
      variation. Early-onset breast cancer occupies a considerable proportion of breast
      cancers in Asian populations, but the reason for this is unclear. We aimed to
      examine miRNA expression profiles in different age-onset groups and pathological
      subtypes in Asian breast cancer. METHODS: At the first stage, 10 samples (tumor:
      n = 6, normal tissue: n = 4) were analyzed with an Agilent microRNA 470 probe
      microarray. Candidate miRNAs with expression levels that were significantly
      altered in breast cancer samples or selected from a literature review were
      further validated by quantitative real-time PCR (qPCR) of 145 breast cancer
      samples at the second stage of the process. Correlations between
      clinicopathological parameters of breast cancer patients from different age
      groups and candidate miRNA expression were elucidated. RESULTS: In the present
      study, the tumor subtypes were significantly different in each age group, and an
      onset age below 40 had poor disease-free and overall survival rates. For all
      breast cancer patients, miR-335 and miR-145 were down-regulated, and miR-21, miR
      200a, miR-200c, and miR-141 were up-regulated. In very young patients (age < 35
      y/o), the expression of 3 and 8 specific miRNAs were up- and down-regulated,
      respectively. In young patients (36-40 y/o), 3 and 3 specific miRNAs were up- and
      down-regulated, respectively. miR-532-5p was up-regulated in triple-negative
      breast cancer. CONCLUSIONS: Differential miRNA expressions between normal and
      tumor tissues were observed in different age groups and tumor subtypes.
      Evolutionarily conserved miRNA clusters, which initiate malignancy
      transformation, were up-regulated in the breast cancers of very young patients.
      None of the significantly altered miRNAs were observed in postmenopausal
      patients.

PMID- 29324833
TI  - Evidence for PMAT- and OCT-like biogenic amine transporters in a probiotic strain
      of Lactobacillus: Implications for interkingdom communication within the
      microbiota-gut-brain axis.
AB  - The ability of prokaryotic microbes to produce and respond to neurochemicals that
      are more often associated with eukaryotic systems is increasingly recognized
      through the concept of microbial endocrinology. Most studies have described the
      phenomena of neurochemical production by bacteria, but there remains an
      incomplete understanding of the mechanisms by which microbe- or host-derived
      neuroactive substances can be recognized by bacteria. Based on the evolutionary
      origins of eukaryotic solute carrier transporters, we hypothesized that bacteria
      may possess an analogous uptake function for neuroactive biogenic amines. Using
      specific fluorescence-based assays, Lactobacillus salivarius biofilms appear to
      express both plasma membrane monoamine transporter (PMAT)- and organic cation
      transporter (OCT)-like uptake of transporter-specific fluorophores. This
      phenomenon is not distributed throughout the genus Lactobacillus as L. rhamnosus
      biofilms did not take up these fluorophores. PMAT probe uptake into L. salivarius
      biofilms was attenuated by the protonophore CCCP, the cation transport inhibitor
      decynium-22, and the natural substrates norepinephrine, serotonin and fluoxetine.
      These results provide the first evidence, to our knowledge, for the existence of
      PMAT- and OCT-like uptake systems in a bacterium. They also suggest the existence
      of a hitherto unrecognized mechanism by which a probiotic bacterium may interact
      with host signals and may provide a means to examine microbial endocrinology
      based interactions in health and disease that are part of the larger microbiota
      gut-brain axis.

PMID- 29324834
TI  - Experimental transmission of West Nile Virus and Rift Valley Fever Virus by Culex
      pipiens from Lebanon.
AB  - West Nile virus (WNV) and Rift Valley fever virus (RVFV) are two emerging
      arboviruses transmitted by Culex pipiens species that includes two biotypes:
      pipiens and molestus. In Lebanon, human cases caused by WNV and RVFV have never
      been reported. However, the introduction of these viruses in the country is
      likely to occur through the migratory birds and animal trades. In this study, we
      evaluated the ability of Cx. pipiens, a predominant mosquito species in urban and
      rural regions in Lebanon, to transmit WNV and RVFV. Culex egg rafts were
      collected in the West Bekaa district, east of Lebanon and adult females of Cx.
      pipiens were experimentally infected with WNV and RVFV Clone 13 strain at titers
      of 1.6*108 and 1.33*107 plaque forming units (PFU)/mL, respectively. We estimated
      viral infection, dissemination and transmission at 3, 7, 14 and 19 days post
      infection (dpi). Results showed that infection was higher for WNV than for RVFV
      from 3 dpi to 19 dpi. Viral dissemination and transmission started from 3 dpi for
      WNV; and only from 19 dpi for RVFV. Moreover, Cx. pipiens were able to excrete in
      saliva a higher number of viral particles of WNV (1028 +/- 405 PFU/saliva at 19
      dpi) than RVFV (42 PFU/saliva at 19 dpi). Cx. pipiens from Lebanon are efficient
      experimental vectors of WNV and to a lower extent, RVFV. These findings should
      stimulate local authorities to establish an active entomological surveillance in
      addition to animal surveys for both viruses in the country.

PMID- 29324835
TI  - Subject-specific pulse wave propagation modeling: Towards enhancement of
      cardiovascular assessment methods.
AB  - Cardiovascular diseases are the leading cause of death worldwide. Pulse wave
      analysis (PWA) technique, which reconstructs and analyses aortic pressure
      waveform based on non-invasive peripheral pressure recording, became an important
      bioassay for cardiovascular assessment in a general population. The aim of our
      study was to establish a pulse wave propagation modeling framework capable of
      matching clinical PWA data from healthy individuals on a per-subject basis.
      Radial pressure profiles from 20 healthy individuals (10 males, 10 females), with
      mean age of 42 +/- 10 years, were recorded using applanation tonometry
      (SphygmoCor, AtCor Medical, Australia) and used to estimate subject-specific
      parameters of mathematical model of blood flow in the system of fifty-five
      arteries. The model was able to describe recorded pressure profiles with high
      accuracy (mean absolute percentage error of 1.87 +/- 0.75%) when estimating only
      6 parameters for each subject. Cardiac output (CO) and stroke volume (SV) have
      been correctly identified by the model as lower in females than males (CO of 3.57
      +/- 0.54 vs. 4.18 +/- 0.72 L/min with p-value < 0.05; SV of 49.5 +/- 10.1 vs.
      64.2 +/- 16.8 ml with p-value = 0.076). Moreover, the model identified age
      related changes in the heart function, i.e. that the cardiac output at rest is
      maintained with age (r = 0.23; p-value = 0.32) despite the decreasing heart rate
      (r = -0.49; p-value < 0.05), because of the increase in stroke volume (r = 0.46;
      p-value < 0.05). Central PWA indices derived from recorded waveforms strongly
      correlated with those obtained using corresponding model-predicted radial waves
      (r > 0.99 and r > 0.97 for systolic (SP) and diastolic (DP) pressures,
      respectively; r > 0.77 for augmentation index (AI); all p-values < 0.01). Model
      predicted central waveforms, however, had higher SP than those reconstructed by
      PWA using recorded radial waves (5.6 +/- 3.3 mmHg on average). From all estimated
      subject-specific parameters only the time to the peak of heart ejection profile
      correlated with clinically measured AI. Our study suggests that the proposed
      model may serve as a tool to computationally investigate virtual patient
      scenarios mimicking different cardiovascular abnormalities. Such a framework can
      augment our understanding and help with the interpretation of PWA results.

PMID- 29324836
TI  - Variation in angler distribution and catch rates of stocked rainbow trout in a
      small reservoir.
AB  - We investigated the spatial and temporal relationship of catch rates and angler
      party location for two days following a publicly announced put-and-take stocking
      of rainbow trout (Oncorhynchus mykiss). Catch rates declined with time since
      stocking and distance from stocking. We hypothesized that opportunity for high
      catch rates would cause anglers to fish near the stocking location and disperse
      with time, however distance between angler parties and stocking was highly
      variable at any given time. Spatially explicit differences in catch rates can
      affect fishing quality. Further research could investigate the variation between
      angler distribution and fish distribution within a waterbody.

PMID- 29324837
TI  - Health economic assessment of Gd-EOB-DTPA MRI versus ECCM-MRI and multi-detector
      CT for diagnosis of hepatocellular carcinoma in China.
AB  - Limited data exists in China on the comparative cost of gadolinium ethoxybenzyl
      diethylenetriamine magnetic resonance imaging (Gd-EOB-DTPA-MRI) with other
      imaging techniques. This study compared the total cost of Gd-EOB-DTPA-MRI with
      multidetector computed tomography (MDCT) and extracellular contrast media
      enhanced MRI (ECCM-MRI) as initial imaging procedures in patients with suspected
      hepatocellular carcinoma (HCC). We developed a decision-tree model on the basis
      of the Chinese clinical guidelines for HCC, which was validated by clinical
      experts from China. The model compared the diagnostic accuracy and costs of
      alternative initial imaging procedures. Compared with MDCT and ECCM-MRI, Gd-EOB
      DTPA-MRI imaging was associated with higher rates of diagnostic accuracy, i.e.
      higher proportions of true positives (TP) and true negatives (TN) with lower
      false positives (FP). Total diagnosis and treatment cost per patient after the
      initial Gd-EOB-DTPA-MRI evaluation was similar to MDCT (Y30,360 vs. Y30,803) and
      lower than that reported with ECCM-MRI (Y30,360 vs. Y31,465). Lower treatment
      cost after initial Gd-EOB-DTPA-MRI was driven by reduced utilization of
      confirmatory diagnostic procedures and unnecessary treatments. The findings
      reported that Gd-EOB-DTPA-MRI offered higher diagnostic accuracy compared with
      MDCT and ECCM-MRI at a comparable cost, which indicates Gd-EOB-DTPA-MRI could be
      the preferred initial imaging procedure for the diagnosis of HCC in China.

PMID- 29324839
TI  - Wild, insectivorous bats might be carriers of Campylobacter spp.
AB  - BACKGROUND: The transmission cycles of the foodborne pathogens Campylobacter and
      Salmonella are not fully elucidated. Knowledge of these cycles may help reduce
      the transmission of these pathogens to humans. METHODOLOGY/PRINCIPAL FINDINGS:
      The presence of campylobacters and salmonellas was examined in 631 fresh fecal
      samples of wild insectivorous bats using a specially developed method for the
      simultaneous isolation of low numbers of these pathogens in small-sized fecal
      samples (<= 0.1 g). Salmonella was not detected in the feces samples, but
      thermotolerant campylobacters were confirmed in 3% (n = 17) of the bats examined
      and these pathogens were found in six different bat species, at different sites,
      in different ecosystems during the whole flying season of bats. Molecular typing
      of the 17 isolated strains indicated C. jejuni (n = 9), C. coli (n = 7) and C.
      lari (n = 1), including genotypes also found in humans, wildlife, environmental
      samples and poultry. Six strains showed unique sequence types.
      CONCLUSION/SIGNIFICANCE: This study shows that insectivorous bats are not only
      carriers of viral pathogens, but they can also be relevant for the transmission
      of bacterial pathogens. Bats should be considered as carriers and potential
      transmitters of Campylobacter and, where possible, contact between bats (bat
      feces) and food or feed should be avoided.

PMID- 29324838
TI  - Canine visceral leishmaniasis: Diagnosis and management of the reservoir living
      among us.
AB  - This article reviews essential topics of canine visceral leishmaniasis (CVL) due
      to Leishmania infantum infection. It focuses on the current serological and
      molecular diagnostic methods used in epidemiological research and veterinary
      clinics to diagnose CVL and includes new point-of-care (POC) tests under
      development. The efficacy of different treatment regimens on the clinical
      improvement and infectiousness of dogs is also addressed. In the last section,
      the review provides a critical appraisal of the effectiveness of different
      control measures that have been implemented to curb disease transmission.

PMID- 29324840
TI  - Malaria increased the risk of stunting and wasting among young children in
      Ethiopia: Results of a cohort study.
AB  - INTRODUCTION: Given the high prevalence of malnutrition in a malaria-endemic
      setting, improving nutritional status could serve as a tool to prevent malaria.
      However, the relationship between the two conditions remains unclear. Therefore,
      this study assessed the association between under-nutrition and malaria among a
      cohort of children aged 6 to 59 months old. METHODS: Two cohorts of children were
      followed for 89 weeks in a rural Rift Valley area of Ethiopia. In the first
      approach (malaria-malnutrition), a cohort of 2,330 non-stunted and 4,204 non
      wasted children were included to assess under-nutrition (outcome) based on their
      previous malaria status (exposure). In the second approach (malnutrition
      malaria), a cohort of 4,468 children were followed-up to measure malaria
      (outcome), taking under-nutrition as an exposure. A weekly home visit was carried
      out to identify malaria cases. Four anthropometry surveys were conducted, and
      generalized estimating equation (GEE) method was used to measure the association
      between undernutrition and malaria. RESULTS: The prevalence of stunting was 44.9%
      in December 2014, 51.5% in August 2015, 50.7% in December 2015 and 48.1% in
      August 2016. We observed 103 cases with 118 episodes of malaria, 684 new stunting
      and 239 new wasting cases. The incidence rate per 10,000 weeks of observation was
      3.8 for malaria, 50.4 for stunting and 8.2 for wasting. Children with malaria
      infection, [Adjusted Odds Ratio (AOR) = 1.9; 95% Confidence Interval (CI), 1.2
      2.9)] and younger age (AOR = 1.3; 95% CI, 1.1-1.5) were more likely to be
      stunted. Furthermore, children with malaria infection (AOR = 8.5; 95% CI, 5.0
      14.5) and young age group (AOR = 1.6; 95% CI, 1.2-2.1) were more likely to be
      wasted. However, stunting and wasting were not risk factors of subsequent malaria
      illness. CONCLUSIONS: Malaria infection was a risk factor for stunting and
      wasting, but stunting or wasting was not associated with subsequent malaria
      illness. As our study shows that malaria is a risk factor for stunting and
      wasting, a close follow-up of the nutritional status of such children may be
      needed. TRIAL REGISTRATION: PACT R2014 11000 882128 (8 September 2014).

PMID- 29324841
TI  - Honey bee (Apis mellifera) nurses do not consume pollens based on their
      nutritional quality.
AB  - Honey bee workers (Apis mellifera) consume a variety of pollens to meet the
      majority of their requirements for protein and lipids. Recent work indicates that
      honey bees prefer diets that reflect the proper ratio of nutrients necessary for
      optimal survival and homeostasis. This idea relies on the precept that honey bees
      evaluate the nutritional composition of the foods provided to them. While this
      has been shown in bumble bees, the data for honey bees are mixed. Further, there
      is controversy as to whether foragers can evaluate the nutritional value of
      pollens, especially if they do not consume it. Here, we focused on nurse workers,
      who eat most of the pollen coming into the hive. We tested the hypothesis that
      nurses prefer diets with higher nutritional value. We first determined the
      nutritional profile, number of plant taxa (richness), and degree of
      hypopharyngeal gland (HG) growth conferred by three honey bee collected pollens.
      We then presented nurses with these same three pollens in paired choice assays
      and measured consumption. To further test whether nutrition influenced
      preference, we also presented bees with natural pollens supplemented with protein
      or lipids and liquid diets with protein and lipid ratios equal to the natural
      pollens. Different pollens conferred different degrees of HG growth, but despite
      these differences, nurse bees did not always prefer the most nutritious pollens.
      Adding protein and/or lipids to less desirable pollens minimally increased pollen
      attractiveness, and nurses did not exhibit a strong preference for any of the
      three liquid diets. We conclude that different pollens provide different
      nutritional benefits, but that nurses either cannot or do not assess pollen
      nutritional value. This implies that the nurses may not be able to communicate
      information about pollen quality to the foragers, who regulate the pollens coming
      into the hive.

PMID- 29324842
TI  - Effect of analytical treatment interruption and reinitiation of antiretroviral
      therapy on HIV reservoirs and immunologic parameters in infected individuals.
AB  - Therapeutic strategies aimed at achieving antiretroviral therapy (ART)-free HIV
      remission in infected individuals are under active investigation. Considering the
      vast majority of HIV-infected individuals experience plasma viral rebound upon
      cessation of therapy, clinical trials evaluating the efficacy of curative
      strategies would likely require inclusion of ART interruption. However, it is
      unclear what impact short-term analytical treatment interruption (ATI) and
      subsequent reinitiation of ART have on immunologic and virologic parameters of
      HIV-infected individuals. Here, we show a significant increase of HIV burden in
      the CD4+ T cells of infected individuals during ATI that was correlated with the
      level of plasma viral rebound. However, the size of the HIV reservoirs as well as
      immune parameters, including markers of exhaustion and activation, returned to
      pre-ATI levels 6-12 months after the study participants resumed ART. Of note, the
      proportions of near full-length, genome-intact and structurally defective HIV
      proviral DNA sequences were similar prior to ATI and following reinitiation of
      ART. In addition, there was no evidence of emergence of antiretroviral drug
      resistance mutations within intact HIV proviral DNA sequences following
      reinitiation of ART. These data demonstrate that short-term ATI does not
      necessarily lead to expansion of the persistent HIV reservoir nor irreparable
      damages to the immune system in the peripheral blood, warranting the inclusion of
      ATI in future clinical trials evaluating curative strategies.

PMID- 29324845
TI  - Soil microbial communities and enzyme activities in sea-buckthorn (Hippophae
      rhamnoides) plantation at different ages.
AB  - The aim of this study was to assess the impact of forest age and season on the
      soil microbial community and enzyme activities in sea-buckthorn plantation system
      and to determine the relative contributions to soil microbial properties. Soil
      sampling was carried out in the dry season (April) and wet season (September) in
      four areas, including: abandoned farmland (NH), an 8-year- old plantation (young
      plantation, 8Y), a 13-year-old plantation (middle-aged plantation, 13Y), and an
      18-year-old plantation (mature plantation, 18Y). The results showed that forest
      age and season have a significant effect on soil microbial community structure
      and enzyme activities. The total, bacterial, fungal, Gram-negative (G+), and Gram
      positive (G-) PLFAs increased gradually with forest age, with the highest values
      detected in 18Y. All the detected enzyme activities showed the trend as a
      consequence of forest age. The microbial PLFAs and soil enzyme activities were
      higher in the wet season than the dry season. However, there were no significant
      interactions between forest age and season. A Correlation analysis suggested that
      soil microbial communities and enzyme activities were significantly and
      positively correlated with pH, total nitrogen (TN) and available phosphorus (AP).
      Season had a stronger influence on soil microbial communities than forest age. In
      general, sea-buckthorn plantations establishment might be a potential tool for
      maintaining and increasing soil fertility in arid and semi-arid regions.

PMID- 29324846
TI  - Correction: Hydrogen sulfide alleviates postharvest ripening and senescence of
      banana by antagonizing the effect of ethylene.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0180113.].

PMID- 29324844
TI  - Absence of myeloid Klf4 reduces prostate cancer growth with pro-atherosclerotic
      activation of tumor myeloid cells and infiltration of CD8 T cells.
AB  - The microenvironment of prostate cancer often includes abundant tumor-associated
      macrophages (TAMs), with their acquisition of an M2 phenotype correlating with
      local aggressiveness and metastasis. Tumor-derived M-CSF contributes to TAM M2
      polarization, and M-CSF receptor inhibition slows prostate cancer growth in model
      systems. As additional cytokines can direct TAM M2 polarization, targeting
      downstream transcription factors could avoid resistance. Klf4 and C/EBPbeta each
      contribute to monocyte development, and reduced expression of macrophage Klf4 or
      C/EBPbeta favors their adoption of a pro-inflammatory M1 state. We find that a Hi
      Myc C57BL/6 prostate cancer line grows more slowly in syngeneic Klf4(f/f);Lys-Cre
      compared with Klf4(f/f) mice when inoculated subcutaneously, but grows equally
      rapidly in C/EBPbeta(f/f);Lys-Cre and C/EBPbeta(f/f) hosts. In the absence of
      myeloid Klf4, TAMs have reduced expression of surface mannose receptor and Fizz1
      mRNA, both M2 markers. Global gene expression analysis further revealed
      activation of pro-inflammatory, pro-atherosclerotic pathways. Analysis of tumor
      infiltrating lymphocytes (TILs) demonstrated markedly increased activated CD8 T
      cell numbers, and CD8 T cell depletion obviated the inhibitory effect of myeloid
      Klf4 deletion on prostate cancer growth. These findings suggest that reducing
      expression or activity of the Klf4 transcription factor in tumor myeloid cells
      may contribute to prostate cancer therapy.

PMID- 29324843
TI  - Beta HPV38 oncoproteins act with a hit-and-run mechanism in ultraviolet radiation
      induced skin carcinogenesis in mice.
AB  - Cutaneous beta human papillomavirus (HPV) types are suspected to be involved,
      together with ultraviolet (UV) radiation, in the development of non-melanoma skin
      cancer (NMSC). Studies in in vitro and in vivo experimental models have
      highlighted the transforming properties of beta HPV E6 and E7 oncoproteins.
      However, epidemiological findings indicate that beta HPV types may be required
      only at an initial stage of carcinogenesis, and may become dispensable after full
      establishment of NMSC. Here, we further investigate the potential role of beta
      HPVs in NMSC using a Cre-loxP-based transgenic (Tg) mouse model that expresses
      beta HPV38 E6 and E7 oncogenes in the basal layer of the skin epidermis and is
      highly susceptible to UV-induced carcinogenesis. Using whole-exome sequencing, we
      show that, in contrast to WT animals, when exposed to chronic UV irradiation K14
      HPV38 E6/E7 Tg mice accumulate a large number of UV-induced DNA mutations, which
      increase proportionally with the severity of the skin lesions. The mutation
      pattern detected in the Tg skin lesions closely resembles that detected in human
      NMSC, with the highest mutation rate in p53 and Notch genes. Using the Cre-lox
      recombination system, we observed that deletion of the viral oncogenes after
      development of UV-induced skin lesions did not affect the tumour growth.
      Together, these findings support the concept that beta HPV types act only at an
      initial stage of carcinogenesis, by potentiating the deleterious effects of UV
      radiation.

PMID- 29324847
TI  - Sabina chinensis and Liriodendron chinense improve air quality in Beijing, China.
AB  - Urban forests have been shown to be efficient for reducing air pollutants
      especially for particulate matters (PMs). This study aims to reveal the PM
      blocking capacity of two common artificial landscape species, Sabina chinensis
      and Liriodendron chinense and to investigate spatial-temporal heterogeneities by
      estimating the vegetation collection velocity of coarse (PM10) and fine particles
      (PM2.5) during different seasons and heights. PM concentration and meteorological
      data were collected on both leeward and windward sides of trees during the
      daytime in both summers and winters from 2013 to 2015. Concentration and
      meteorological monitors were installed at three heights, bottom (1.5 m), middle
      (3.5 m), and top (5.5 m) of the canopy. The results showed: During daytime, the
      collection velocity changed and PM2.5 collection velocity was much higher than
      that of PM10. Furthermore, the maximum collection velocities of L. chinense and
      S. chinensis occurred at 14:00-16:00 both in summer and winter. Moreover, the
      collection velocity had a positive correlation with wind speed and temperature.
      The blocking capacities of L. chinense and S. chinensis varied from season to
      season, and the concentrations of particulate matter indicate the middle canopy
      of both species as the most effective part for TSP blocking. Furthermore, these
      two species are more effective blocking in PM2.5 than PM10. The blocking capacity
      of S. chinensis is generally better. The vegetation collection is the major
      process of PM removal near the ground and sedimentation was not taken into
      consideration near the ground.

PMID- 29324848
TI  - Platelet-rich plasma to treat experimentally-induced skin wounds in animals: A
      systematic review and meta-analysis.
AB  - The objective of the study was to review current literature to determine whether
      the topical application of platelet-rich plasma (PRP) promotes healing in
      experimentally-induced full-thickness skin wounds in animals. The hypothesis was
      that the adjunct of PRP has a positive effect on wound healing. An electronic
      search was carried out on the following databases: Web of Science, Cochrane
      Library, PubMed, Research Gate, Cochrane Wounds Group, Veterinary Information
      Network. No publication date nor language restrictions were applied. Randomised
      and not randomised controlled clinical trials comparing PRP with placebo or with
      other treatments were included. The reduction of open wound area in PRP-treated
      (test) wounds compared to control wounds was the primary outcome. Secondary
      outcomes were healing time and number of healed cases in test group compared to
      control. The following effect sizes were calculated: the Hedges' g for continuous
      variables; the odds ratio for binary data. Eighteen controlled clinical trials
      were included in the qualitative and quantitative synthesis, with a total of 661
      wounds. All studies were published in the period 2007-2016. Eight studies were
      carried out on rodent/lagomorph mammals and 10 on non-rodent/lagomorph mammals.
      In all included studies, control wounds underwent placebo or were left untreated.
      The PRP group showed a better healing performance than the control group in each
      outcome. The effect size was statistically significant considering the primary
      outcome and the overall aggregation of the three outcomes. The effect size,
      although in favour of the treatment with PRP, was not significant considering the
      healing time and the number of healings. The overall heterogeneity was mild or
      moderate. Five studies reported a high risk of selection bias. The publication
      bias was always mild or absent. The results support the hypothesis of the
      positive effects of the PRP when compared to control groups in the treatment of
      experimentally-induced full-thickness skin wounds in animals. PRP can therefore
      be considered an effective adjunctive therapy in stimulating second intention
      healing of acute wounds in healthy animals.

PMID- 29324849
TI  - The B cell death function of obinutuzumab-HDEL produced in plant (Nicotiana
      benthamiana L.) is equivalent to obinutuzumab produced in CHO cells.
AB  - Plants have attracted attention as bio-drug production platforms because of their
      economical and safety benefits. The preliminary efficacy of ZMapp, a cocktail of
      antibodies produced in N. benthamiana (Nicotiana benthamiana L.), suggested
      plants may serve as a platform for antibody production. However, because the
      amino acid sequences of the Fab fragment are diverse and differences in post
      transcriptional processes between animals and plants remain to be elucidated, it
      is necessary to confirm functional equivalence of plant-produced antibodies to
      the original antibody. In this study, Obinutuzumab, a third generation anti-CD20
      antibody, was produced in N. benthamiana leaves (plant-obinutuzumab) and compared
      to the original antibody produced in glyco-engineered Chinese hamster ovary (CHO)
      cells (CHO-obinutuzumab). Two forms (with or without an HDEL tag) were generated
      and antibody yields were compared. The HDEL-tagged form was more highly expressed
      than the non-HDEL-tagged form which was cleaved in the N-terminus. To determine
      the equivalence in functions of the Fab region between the two forms, we compared
      the CD20 binding affinities and direct binding induced cell death of a CD20
      positive B cells. Both forms showed similar CD20 binding affinities and direct
      cell death of B cell. The results suggested that plant-obinutuzumab was
      equivalent to CHO-obinutuzumab in CD20 binding, cell aggregation, and direct cell
      death via binding. Therefore, our findings suggest that Obinutuzumab is a
      promising biosimilar candidate that can be produced efficiently in plants.

PMID- 29324850
TI  - Generalization of the Ewens sampling formula to arbitrary fitness landscapes.
AB  - In considering evolution of transcribed regions, regulatory sequences, and other
      genomic loci, we are often faced with a situation in which the number of allelic
      states greatly exceeds the size of the population. In this limit, the population
      eventually adopts a steady state characterized by mutation-selection-drift
      balance. Although new alleles continue to be explored through mutation, the
      statistics of the population, and in particular the probabilities of seeing
      specific allelic configurations in samples taken from the population, do not
      change with time. In the absence of selection, the probabilities of allelic
      configurations are given by the Ewens sampling formula, widely used in population
      genetics to detect deviations from neutrality. Here we develop an extension of
      this formula to arbitrary fitness distributions. Although our approach is
      general, we focus on the class of fitness landscapes, inspired by recent high
      throughput genotype-phenotype maps, in which alleles can be in several distinct
      phenotypic states. This class of landscapes yields sampling probabilities that
      are computationally more tractable and can form a basis for inference of
      selection signatures from genomic data. Using an efficient numerical
      implementation of the sampling probabilities, we demonstrate that, for a sizable
      range of mutation rates and selection coefficients, the steady-state allelic
      diversity is not neutral. Therefore, it may be used to infer selection
      coefficients, as well as other evolutionary parameters from population data. We
      also carry out numerical simulations to challenge various approximations involved
      in deriving our sampling formulas, such as the infinite-allele limit and the
      "full connectivity" assumption inherent in the Ewens theory, in which each allele
      can mutate into any other allele. We find that, at least for the specific
      numerical examples studied, our theory remains sufficiently accurate even if
      these assumptions are relaxed. Thus our framework establishes both theoretical
      and practical foundations for inferring selection signatures from population
      level genomic sequence samples.

PMID- 29324851
TI  - Development and validation of the Vietnamese primary care assessment tool.
AB  - OBJECTIVE: To adapt the consumer version of the Primary Care Assessment Tool
      (PCAT) for Vietnam and determine its internal consistency and validity. DESIGN: A
      quantitative cross sectional study. SETTING: 56 communes in 3 representative
      provinces of central Vietnam. PARTICIPANTS: Total of 3289 people who used health
      care services at health facility at least once over the past two years. RESULTS:
      The Vietnamese adult expanded consumer version of the PCAT (VN PCAT-AE) is an
      instrument for evaluation of primary care in Vietnam with 70 items comprising six
      scales representing four core primary care domains, and three additional scales
      representing three derivative domains. Sixteen other items from the original tool
      were not included in the final instrument, due to problems with missing values,
      floor or ceiling effects, and item-total correlations. All the retained scales
      have a Cronbach's alpha above 0.70 except for the subscale of Family
      Centeredness. CONCLUSIONS: The VN PCAT-AE demonstrates adequate internal
      consistency and validity to be used as an effective tool for measuring the
      quality of primary care in Vietnam from the consumer perspective. Additional work
      in the future to optimize valid measurement in all domains consistent with the
      original version of the tool may be helpful as the primary care system in Vietnam
      further develops.

PMID- 29324852
TI  - Real-life helping behaviours in North America: A genome-wide association
      approach.
AB  - In humans, prosocial behaviour is essential for social functioning. Twin studies
      suggest this distinct human trait to be partly hardwired. In the last decade
      research on the genetics of prosocial behaviour focused on neurotransmitters and
      neuropeptides, such as oxytocin, dopamine, and their respective pathways. Recent
      trends towards large scale medical studies targeting the genetic basis of complex
      diseases such as Alzheimer's disease and schizophrenia pave the way for new
      directions also in behavioural genetics. Based on data from 10,713 participants
      of the American Health and Retirement Study we estimated heritability of helping
      behaviour-its total variance explained by 1.2 million single nucleotide
      polymorphisms-to be 11%. Both, fixed models and mixed linear models identified
      rs11697300, an intergene variant on chromosome 20, as a candidate variant
      moderating this particular helping behaviour. We assume that this so far
      undescribed area is worth further investigation in association with human
      prosocial behaviour.

PMID- 29324853
TI  - Disentangling and modeling interactions in fish with burst-and-coast swimming
      reveal distinct alignment and attraction behaviors.
AB  - The development of tracking methods for automatically quantifying individual
      behavior and social interactions in animal groups has open up new perspectives
      for building quantitative and predictive models of collective behavior. In this
      work, we combine extensive data analyses with a modeling approach to measure,
      disentangle, and reconstruct the actual functional form of interactions involved
      in the coordination of swimming in Rummy-nose tetra (Hemigrammus rhodostomus).
      This species of fish performs burst-and-coast swimming behavior that consists of
      sudden heading changes combined with brief accelerations followed by quasi
      passive, straight decelerations. We quantify the spontaneous stochastic behavior
      of a fish and the interactions that govern wall avoidance and the reaction to a
      neighboring fish, the latter by exploiting general symmetry constraints for the
      interactions. In contrast with previous experimental works, we find that both
      attraction and alignment behaviors control the reaction of fish to a neighbor. We
      then exploit these results to build a model of spontaneous burst-and-coast
      swimming and interactions of fish, with all parameters being estimated or
      directly measured from experiments. This model quantitatively reproduces the key
      features of the motion and spatial distributions observed in experiments with a
      single fish and with two fish. This demonstrates the power of our method that
      exploits large amounts of data for disentangling and fully characterizing the
      interactions that govern collective behaviors in animals groups.

PMID- 29324854
TI  - Characterization of the biosynthetic gene cluster for cryptic phthoxazolin A in
      Streptomyces avermitilis.
AB  - Phthoxazolin A, an oxazole-containing polyketide, has a broad spectrum of anti
      oomycete activity and herbicidal activity. We recently identified phthoxazolin A
      as a cryptic metabolite of Streptomyces avermitilis that produces the important
      anthelmintic agent avermectin. Even though genome data of S. avermitilis is
      publicly available, no plausible biosynthetic gene cluster for phthoxazolin A is
      apparent in the sequence data. Here, we identified and characterized the
      phthoxazolin A (ptx) biosynthetic gene cluster through genome sequencing,
      comparative genomic analysis, and gene disruption. Sequence analysis uncovered
      that the putative ptx biosynthetic genes are laid on an extra genomic region that
      is not found in the public database, and 8 open reading frames in the extra
      genomic region could be assigned roles in the biosynthesis of the oxazole ring,
      triene polyketide and carbamoyl moieties. Disruption of the ptxA gene encoding a
      discrete acyltransferase resulted in a complete loss of phthoxazolin A
      production, confirming that the trans-AT type I PKS system is responsible for the
      phthoxazolin A biosynthesis. Based on the predicted functional domains in the ptx
      assembly line, we propose the biosynthetic pathway of phthoxazolin A.

PMID- 29324856
TI  - Correction: Minimally invasive monitoring of CD4 T cells at multiple mucosal
      tissues after intranasal vaccination in rhesus macaques.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0188807.].

PMID- 29324855
TI  - CTLs, a new class of RING-H2 ubiquitin ligases uncovered by YEELL, a motif close
      to the RING domain that is present across eukaryotes.
AB  - RING ubiquitin E3 ligases enclose a RING domain for ubiquitin ligase activity and
      associated domains and/or conserved motifs outside the RING domain that
      collectively facilitate their classification and usually reveal some of key
      information related to mechanism of action. Here we describe a new family of E3
      ligases that encodes a RING-H2 domain related in sequence to the ATL and BTL RING
      H2 domains. This family, named CTL, encodes a motif designed as YEELL that
      expands 21 amino acids next to the RING-H2 domain that is present across most
      eukaryotic lineages. E3 ubiquitin ligase BIG BROTHER is a plant CTL that
      regulates organ size, and SUMO-targeted ubiquitin E3 ligase RNF111/ARKADIA is a
      vertebrate CTL. Basal animal and vertebrate, as well as fungi species, encode a
      single CTL gene that constraints the number of paralogs observed in vertebrates.
      Conversely, as previously described in ATL and BTL families in plants, CTL genes
      range from a single copy in green algae and 3 to 5 copies in basal species to 9
      to 35 copies in angiosperms. Our analysis describes key structural features of a
      novel family of E3 ubiquitin ligases as an integral component of the set of core
      eukaryotic genes.

PMID- 29324857
TI  - Allergic rhinitis and rhinosinusitis synergistically compromise the mental health
      and health-related quality of life of Korean adults: A nationwide population
      based survey.
AB  - BACKGROUND: Allergic rhinitis (AR) and rhinosinusitis (RS) negatively impact
      psychological well-being and health-related quality of life (HRQoL). However, few
      population-based studies have investigated the effects of these conditions on
      mental health and HRQoL. PURPOSE: To explore independent associations of AR
      and/or RS with mental health and HRQoL using data from the 2013-2015 Korea
      National Health and Nutrition Examination Survey (KNHANES). METHODS: The KNHANES
      is a nationwide cross-sectional survey of the non-institutionalized population of
      Korea. A total of 15,441 adults completed the clinical examination and the health
      questionnaire. We divided all participants into four groups: AR-/RS-, AR-/RS+,
      AR+/RS-, and AR+/RS+. Logistic regression analyses were performed after
      adjustment for sociodemographic characteristics, general health behaviors, and
      other comorbidities. RESULTS: The AR+/RS+ group contained the highest proportion
      of subjects with perceived stress and depressed mood. Subjects with AR+/RS+ also
      had more frequent problems in terms of pain/discomfort and anxiety/depression.
      After adjusting for all confounders, the odds ratios (ORs) were 2.96 (p = 0.009)
      for depressed mood and 3.17 (p = 0.013) for suicidal ideation in the AR+/RS+
      group compared with in the AR-/RS- group. The AR+/RS- group reported more
      perceived stress (OR, 1.56, p = 0.003) and depression (OR, 1.72, p = 0.024)
      compared with the AR-/RS- group. In terms of the ORs for HRQoL, the AR+/RS+ group
      reported more problems in terms of self-care (OR, 3.73, p = 0.038) and more
      pain/discomfort (OR 2.19, p = 0.006) compared with the AR-/RS- group.
      CONCLUSIONS: In the Korean population, AR and RS exerted a synergistic negative
      impact on mental health and HRQoL, especially suicidal ideation. Most patients
      seek help from clinicians for impaired HRQoL. Therefore, clinicians should
      consider the underlying mental health and HRQoL of patients with AR and/or RS, as
      these may be impaired by their conditions.

PMID- 29324860
TI  - Correction: Polygalacturonase gene pgxB in Aspergillus niger is a virulence
      factor in apple fruit.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0173277.].

PMID- 29324858
TI  - Mapping the geographical distribution of podoconiosis in Cameroon using
      parasitological, serological, and clinical evidence to exclude other causes of
      lymphedema.
AB  - BACKGROUND: Podoconiosis is a non-filarial elephantiasis, which causes massive
      swelling of the lower legs. It was identified as a neglected tropical disease by
      WHO in 2011. Understanding of the geographical distribution of the disease is
      incomplete. As part of a global mapping of podoconiosis, this study was conducted
      in Cameroon to map the distribution of the disease. This mapping work will help
      to generate data on the geographical distribution of podoconiosis in Cameroon and
      contribute to the global atlas of podoconiosis. METHODS: We used a multi-stage
      sampling design with stratification of the country by environmental risk of
      podoconiosis. We sampled 76 villages from 40 health districts from the ten
      Regions of Cameroon. All individuals of 15-years old or older in the village were
      surveyed house-to-house and screened for lymphedema. A clinical algorithm was
      used to reliably diagnose podoconiosis, excluding filarial-associated lymphedema.
      Individuals with lymphoedema were tested for circulating Wuchereria bancrofti
      antigen and specific IgG4 using the Alere Filariasis Test Strips (FTS) test and
      the Standard Diagnostics (SD) BIOLINE lymphatic filariasis IgG4 test (Wb123)
      respectively, in addition to thick blood films. Presence of DNA specific to W.
      bancrofti was checked on night blood using a qPCR technique. PRINCIPAL FINDINGS:
      Overall, 10,178 individuals from 4,603 households participated in the study. In
      total, 83 individuals with lymphedema were identified. Of the 83 individuals with
      lymphedema, two were found to be FTS positive and all were negative using the
      Wb123 test. No microfilaria of W. bancrofti were found in the night blood of any
      individual with clinical lymphedema. None were found to be positive for W.
      bancrofti using qPCR. Of the two FTS positive cases, one was positive for
      Mansonella perstans DNA, while the other harbored Loa loa microfilaria. Overall,
      52 people with podoconiosis were identified after applying the clinical
      algorithm. The overall prevalence of podoconiosis was found to be 0.5% (95%
      [confidence interval] CI; 0.4-0.7). At least one case of podoconiosis was found
      in every region of Cameroon except the two surveyed villages in Adamawa. Of the
      40 health districts surveyed, 17 districts had no cases of podoconiosis; in 15
      districts, mean prevalence was between 0.2% and 1.0%; and in the remaining eight,
      mean prevalence was between 1.2% and 2.7%. CONCLUSIONS: Our investigation has
      demonstrated low prevalence but almost nationwide distribution of podoconiosis in
      Cameroon. Designing a podoconiosis control program is a vital next step. A health
      system response to the burden of podoconiosis is important, through case
      surveillance and morbidity management services.

PMID- 29324859
TI  - Magnetic resonance spectroscopy detects differential lipid composition in mammary
      glands on low fat, high animal fat versus high fructose diets.
AB  - The effects of consumption of different diets on the fatty acid composition in
      the mammary glands of SV40 T-antigen (Tag) transgenic mice, a well-established
      model of human triple-negative breast cancer, were investigated with magnetic
      resonance spectroscopy and spectroscopic imaging. Female C3(1) SV40 Tag
      transgenic mice (n = 12) were divided into three groups at 4 weeks of age: low
      fat diet (LFD), high animal fat diet (HAFD), and high fructose diet (HFruD). MRI
      scans of mammary glands were acquired with a 9.4 T scanner after 8 weeks on the
      diet. 1H spectra were acquired using point resolved spectroscopy (PRESS) from two
      1 mm3 boxes on each side of inguinal mammary gland with no cancers, lymph nodes,
      or lymph ducts. High spectral and spatial resolution (HiSS) images were also
      acquired from nine 1-mm slices. A combination of Gaussian and Lorentzian
      functions was used to fit the spectra. The percentages of poly-unsaturated fatty
      acids (PUFA), mono-unsaturated fatty acids (MUFA), and saturated fatty acids
      (SFA) were calculated from each fitted spectrum. Water and fat peak height images
      (maps) were generated from HiSS data. The results showed that HAFD mice had
      significantly lower PUFA than both LFD (p < 0.001) and HFruD (p < 0.01) mice. The
      mammary lipid quantity calculated from 1H spectra was much larger in HAFD mice
      than in LFD (p = 0.03) but similar to HFruD mice (p = 0.10). The average fat
      signal intensity over the mammary glands calculated from HiSS fat maps was ~60%
      higher in HAFD mice than in LFD (p = 0.04) mice. The mean or median of calculated
      parameters for the HFruD mice were between those for LFD and HAFD mice.
      Therefore, PRESS spectroscopy and HiSS MRI demonstrated water and fat composition
      changes in mammary glands due to a Western diet, which was low in potassium, high
      in sodium, animal fat, and simple carbohydrates. Measurements of PUFA with MRI
      could be used to evaluate cancer risk, improve cancer detection and diagnosis,
      and guide preventative therapy.

PMID- 29324861
TI  - Cost of treatment for head and neck cancer in India.
AB  - There are no published data on the cost of cancer treatment for guiding
      reimbursement decisions in India. The present study was designed to estimate the
      cost of treating head and neck cancer (HNC) with the aim of determining package
      rates. The present study was undertaken in the Departments of Radiotherapy and
      Otolaryngology of a large tertiary care hospital in North India. Economic health
      system costs incurred were assessed using a bottom-up methodology. Data on all
      resources-capital or recurrent, incurred on the delivery of HNC treatment were
      collected from April 2014 to March 2015. Following the cost-of-illness approach,
      patients were interviewed to elicit out-of-pocket (OOP) expenditure. A total of
      INR 40,993,017 (USD 0.67 million) was spent on radiotherapy care for treating HNC
      during 1 year. Salaries constituted the major component (42.6%) of this cost,
      followed by equipment/furniture (29%), space rent (20.7%), overheads and
      consumables (7.7%). In addition, INR 47,191 (USD 773) per HNC patient was spent
      on the surgery. Furthermore, patients spent an average amount ranging from INR
      12,575 (USD 206) to INR 65,257 (USD 1069) on the different treatment therapies.
      In terms of package rates, cobalt radiotherapy alone was the cheapest (INR
      38,714, USD 634), while intensity modulated radiotherapy (IMRT) was most
      expensive (INR 192,914, USD 3161). The estimates from the present study could be
      used for developing package rates under various publicly financed health
      insurance schemes as well as for the planning for creation of new cancer centres.

PMID- 29324863
TI  - Correction: Orion: Detecting regions of the human non-coding genome that are
      intolerant to variation using population genetics.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0181604.].

PMID- 29324862
TI  - Taking two to tango: fMRI analysis of improvised joint action with physical
      contact.
AB  - Many forms of joint action involve physical coupling between the participants,
      such as when moving a sofa together or dancing a tango. We report the results of
      a novel two-person functional MRI study in which trained couple dancers engaged
      in bimanual contact with an experimenter standing next to the bore of the magnet,
      and in which the two alternated between being the leader and the follower of
      joint improvised movements. Leading showed a general pattern of self-orientation,
      being associated with brain areas involved in motor planning, navigation,
      sequencing, action monitoring, and error correction. In contrast, following
      showed a far more sensory, externally-oriented pattern, revealing areas involved
      in somatosensation, proprioception, motion tracking, social cognition, and
      outcome monitoring. We also had participants perform a "mutual" condition in
      which the movement patterns were pre-learned and the roles were symmetric,
      thereby minimizing any tendency toward either leading or following. The mutual
      condition showed greater activity in brain areas involved in mentalizing and
      social reward than did leading or following. Finally, the analysis of
      improvisation revealed the dual importance of motor-planning and working-memory
      areas. We discuss these results in terms of theories of both joint action and
      improvisation.

PMID- 29324865
TI  - Association of circadian rhythm genes ARNTL/BMAL1 and CLOCK with multiple
      sclerosis.
AB  - Prevalence of multiple sclerosis varies with geographic latitude. We hypothesized
      that this fact might be partially associated with the influence of latitude on
      circadian rhythm and consequently that genetic variability of key circadian
      rhythm regulators, ARNTL and CLOCK genes, might contribute to the risk for
      multiple sclerosis. Our aim was to analyse selected polymorphisms of ARNTL and
      CLOCK, and their association with multiple sclerosis. A total of 900 Caucasian
      patients and 1024 healthy controls were compared for genetic signature at 8 SNPs,
      4 for each of both genes. We found a statistically significant difference in
      genotype (ARNTL rs3789327, P = 7.5.10-5; CLOCK rs6811520 P = 0.02) distributions
      in patients and controls. The ARNTL rs3789327 CC genotype was associated with
      higher risk for multiple sclerosis at an OR of 1.67 (95% CI 1.35-2.07, P =
      0.0001) and the CLOCK rs6811520 genotype CC at an OR of 1.40 (95% CI 1.13-1.73, P
      = 0.002). The results of this study suggest that genetic variability in the ARNTL
      and CLOCK genes might be associated with risk for multiple sclerosis.

PMID- 29324866
TI  - Regulation of influenza virus replication by Wnt/beta-catenin signaling.
AB  - Wnt/beta-catenin signaling is an essential pathway in cell cycle control.
      Dysregulation of the Wnt/beta-catenin signaling pathway during viral infection
      has been reported. In this study, we examined the effect of modulating Wnt/beta
      catenin signaling during influenza virus infection. The activation of the
      Wnt/beta-catenin pathway by Wnt3a increased influenza virus mRNA and virus
      production in in vitro in mouse lung epithelial E10 cells and mRNA expresson of
      influenza virus genes in vivo in the lungs of mice infected with influenza virus
      A/Puerto Rico/8/34. However, the inhibition of Wnt/beta-catenin signaling by
      iCRT14 reduced virus titer and viral gene expression in human lung epithelial
      A549 cells and viral replication in primary mouse alveolar epithelial cells
      infected with different influenza virus strains. Knockdown of beta-catenin also
      reduced viral protein expression and virus production. iCRT14 acts at the early
      stage of virus replication. Treatment with iCRT14 inhibited the expression of the
      viral genes (vRNA, cRNA and mRNA) evaluated in this study. The intraperitoneal
      administration of iCRT14 reduced viral load, improved clinical signs, and
      partially protected mice from influenza virus infection.

PMID- 29324864
TI  - Safety of single low-dose primaquine in glucose-6-phosphate dehydrogenase
      deficient falciparum-infected African males: Two open-label, randomized, safety
      trials.
AB  - BACKGROUND: Primaquine (PQ) actively clears mature Plasmodium falciparum
      gametocytes but in glucose-6-phosphate dehydrogenase deficient (G6PDd)
      individuals can cause hemolysis. We assessed the safety of low-dose PQ in
      combination with artemether-lumefantrine (AL) or dihydroartemisinin-piperaquine
      (DP) in G6PDd African males with asymptomatic P. falciparum malaria. METHODS AND
      FINDINGS: In Burkina Faso, G6PDd adult males were randomized to treatment with AL
      alone (n = 10) or with PQ at 0.25 (n = 20) or 0.40 mg/kg (n = 20) dosage; G6PD
      normal males received AL plus 0.25 (n = 10) or 0.40 mg/kg (n = 10) PQ. In The
      Gambia, G6PDd adult males and boys received DP alone (n = 10) or with 0.25 mg/kg
      PQ (n = 20); G6PD-normal males received DP plus 0.25 (n = 10) or 0.40 mg/kg (n =
      10) PQ. The primary study endpoint was change in hemoglobin concentration during
      the 28-day follow-up. Cytochrome P-450 isoenzyme 2D6 (CYP2D6) metabolizer status,
      gametocyte carriage, haptoglobin, lactate dehydrogenase levels and reticulocyte
      counts were also determined. In Burkina Faso, the mean maximum absolute change in
      hemoglobin was -2.13 g/dL (95% confidence interval [CI], -2.78, -1.49) in G6PDd
      individuals randomized to 0.25 PQ mg/kg and -2.29 g/dL (95% CI, -2.79, -1.79) in
      those receiving 0.40 PQ mg/kg. In The Gambia, the mean maximum absolute change in
      hemoglobin concentration was -1.83 g/dL (95% CI, -2.19, -1.47) in G6PDd
      individuals receiving 0.25 PQ mg/kg. After adjustment for baseline
      concentrations, hemoglobin reductions in G6PDd individuals in Burkina Faso were
      more pronounced compared to those in G6PD-normal individuals receiving the same
      PQ doses (P = 0.062 and P = 0.022, respectively). Hemoglobin levels normalized
      during follow-up. Abnormal haptoglobin and lactate dehydrogenase levels provided
      additional evidence of mild transient hemolysis post-PQ. CONCLUSIONS: Single low
      dose PQ in combination with AL and DP was associated with mild and transient
      reductions in hemoglobin. None of the study participants developed moderate or
      severe anemia; there were no severe adverse events. This indicates that single
      low-dose PQ is safe in G6PDd African males when used with artemisinin-based
      combination therapy. TRIAL REGISTRATION: Clinicaltrials.gov NCT02174900
      Clinicaltrials.gov NCT02654730.

PMID- 29324867
TI  - Comparative transcriptome analysis reveals key genes potentially related to
      soluble sugar and organic acid accumulation in watermelon.
AB  - Soluble sugars and organic acids are important components of fruit flavor and
      have a strong impact on the overall organoleptic quality of watermelon (Citrullus
      lanatus) fruit. Several studies have analyzed the expression levels of the genes
      related to soluble sugar accumulation and the dynamic changes in their content
      during watermelon fruit development and ripening. Nevertheless, to date, there
      have been no reports on the organic acid content in watermelon or the genes
      regulating their synthesis. In this study, the soluble sugars and organic acids
      in watermelon were measured and a comparative transcriptome analysis was
      performed to identify the key genes involved in the accumulation of these
      substances during fruit development and ripening. The watermelon cultivar '203Z'
      and its near-isogenic line (NIL) 'SW' (in the '203Z' background) were used as
      experimental materials. The results suggested that soluble sugar consist of
      fructose, glucose and sucrose while malic-, citric-, and oxalic acids are the
      primary organic acids in watermelon fruit. Several differentially expressed genes
      (DEGs) related to soluble sugar- and organic acid accumulation and metabolism
      were identified. These include the DEGs encoding raffinose synthase, sucrose
      synthase (SuSy), sucrose-phosphate synthase (SPSs), insoluble acid invertases
      (IAI), NAD-dependent malate dehydrogenase (NAD-cyt MDH), aluminum-activated
      malate transporter (ALMT), and citrate synthase (CS). This is the first report
      addressing comparative transcriptome analysis via NILs materials in watermelon
      fruit. These findings provide an important basis for understanding the molecular
      mechanism that leads to soluble sugar and organic acid accumulation and
      metabolism during watermelon fruit development and ripening.

PMID- 29324868
TI  - Effects of pulsed electromagnetic field (PEMF) on the tensile biomechanical
      properties of diabetic wounds at different phases of healing.
AB  - The present study investigated the effects of pulsed electromagnetic field (PEMF)
      on the tensile biomechanical properties of diabetic wounds at different phases of
      healing. Two intensities of PEMF were adopted for comparison. We randomly
      assigned 111 10-week-old male streptozotocin-induced diabetic Sprague-Dawley rats
      to two PEMF groups and a sham control group. Six-millimetre biopsy punched full
      thickness wounds were made on the lateral side of their hindlimbs. The PEMF
      groups received active PEMF delivered at 25 Hz with intensity of either 2 mT or
      10 mT daily, while the sham group was handled in a similar way except they were
      not exposed to PEMF. Wound tissues were harvested for tensile testing on post
      wounding days 3, 5, 7, 10, 14 and 21. Maximum load, maximum stress, energy
      absorption capacity, Young's modulus and thickness of wound tissue were measured.
      On post-wounding day 5, the PEMF group that received 10-mT intensity had
      significantly increased energy absorption capacity and showed an apparent
      increase in the maximum load. However, the 10-mT PEMF group demonstrated a
      decrease in Young's modulus on day 14. The 10-mT PEMF groups showed a significant
      increase in the overall thickness of wound tissue whereas the 2-mT group showed a
      significant decrease in the overall maximum stress of the wounds tissue. The
      present findings demonstrated that the PEMF delivered at 10 mT can improve energy
      absorption capacity of diabetic wounds in the early healing phase. However, PEMF
      (both 2-mT and 10-mT) seemed to impair the material properties (maximum stress
      and Young's modulus) in the remodelling phase. PEMF may be a useful treatment for
      promoting the recovery of structural properties (maximum load and energy
      absorption capacity), but it might not be applied at the remodelling phase to
      avoid impairing the recovery of material properties.

PMID- 29324869
TI  - Exploring the binding sites and binding mechanism for hydrotrope encapsulated
      griseofulvin drug on gamma-tubulin protein.
AB  - The protein gamma-tubulin plays an important role in centrosomal clustering and
      this makes it an attractive therapeutic target for treating cancers.
      Griseofulvin, an antifungal drug, has recently been used to inhibit proliferation
      of various types of cancer cells. It can also affect the microtubule dynamics by
      targeting the gamma-tubulin protein. So far, the binding pockets of gamma-tubulin
      protein are not properly identified and the exact mechanism by which the drug
      binds to it is an area of intense speculation and research. The aim of the
      present study is to investigate the binding mechanism and binding affinity of
      griseofulvin on gamma-tubulin protein using classical molecular dynamics
      simulations. Since the drug griseofulvin is sparingly soluble in water, here we
      also present a promising approach for formulating and achieving delivery of
      hydrophobic griseofulvin drug via hydrotrope sodium cumene sulfonate (SCS)
      cluster. We observe that the binding pockets of gamma-tubulin protein are mainly
      formed by the H8, H9 helices and S7, S8, S14 strands and the hydrophobic
      interactions between the drug and gamma-tubulin protein drive the binding
      process. The release of the drug griseofulvin from the SCS cluster is confirmed
      by the coordination number analysis. We also find hydrotrope-induced alteration
      of the binding sites of gamma-tubulin protein and the weakening of the drug
      protein interactions.

PMID- 29324870
TI  - Incretin responses to oral glucose and mixed meal tests and changes in fasting
      glucose levels during 7 years of follow-up: The Hoorn Meal Study.
AB  - We conducted the first prospective observational study in which we examined the
      association between incretin responses to an oral glucose tolerance test (OGTT)
      and mixed meal test (MMT) at baseline and changes in fasting glucose levels 7
      years later, in individuals who were non-diabetic at baseline. We used data from
      the Hoorn Meal Study; a population-based cohort study among 121 subjects, aged
      61.0+/-6.7y. GIP and GLP-1 responses were determined at baseline and expressed as
      total and incremental area under the curve (tAUC and iAUC). The association
      between incretin response at baseline and changes in fasting glucose levels was
      assessed using linear regression. The average change in glucose over 7 years was
      0.43 +/- 0.5 mmol/l. For GIP, no significant associations were observed with
      changes in fasting glucose levels. In contrast, participants within the middle
      and highest tertile of GLP-1 iAUC responses to OGTT had significantly smaller
      increases (actually decreases) in fasting glucose levels; -0.28 (95% confidence
      interval: -0.54;-0.01) mmol/l and -0.39 (-0.67;-0.10) mmol/l, respectively,
      compared to those in the lowest tertile. The same trend was observed for tAUC GLP
      1 following OGTT (highest tertile: -0.32 (0.61;-0.04) mmol/l as compared to the
      lowest tertile). No significant associations were observed for GLP-1 responses
      following MMT. In conclusion, within our non-diabetic population-based cohort, a
      low GLP-1 response to OGTT was associated with a steeper increase in fasting
      glucose levels during 7 years of follow-up. This suggests that a reduced GLP-1
      response precedes glucose deterioration and may play a role in the etiology of
      type 2 diabetes mellitus.

PMID- 29324872
TI  - lin-4 and the NRDE pathway are required to activate a transgenic lin-4 reporter
      but not the endogenous lin-4 locus in C. elegans.
AB  - As the founding member of the microRNA (miRNA) gene family, insights into lin-4
      regulation and function have laid a conceptual foundation for countless miRNA
      related studies that followed. We previously showed that a transcriptional lin-4
      reporter in C. elegans was positively regulated by a lin-4-complementary element
      (LCE), and by lin-4 itself. In this study, we sought to (1) identify additional
      factors required for lin-4 reporter expression, and (2) validate the endogenous
      relevance of a potential positive autoregulatory mechanism of lin-4 expression.
      We report that all four core nuclear RNAi factors (nrde-1, nrde-2, nrde-3 and
      nrde-4), positively regulate lin-4 reporter expression. In contrast, endogenous
      lin-4 levels were largely unaffected in nrde-2;nrde-3 mutants. Further, an
      endogenous LCE deletion generated by CRISPR-Cas9 revealed that the LCE was also
      not necessary for the activity of the endogenous lin-4 promoter. Finally,
      mutations in mature lin-4 did not reduce primary lin-4 transcript levels. Taken
      together, these data indicate that under growth conditions that reveal effects at
      the transgenic locus, a direct, positive autoregulatory mechanism of lin-4
      expression does not occur in the context of the endogenous lin-4 locus.

PMID- 29324871
TI  - Citrullinated histone H3 as a novel prognostic blood marker in patients with
      advanced cancer.
AB  - Citrullinated histone H3 (H3Cit) is a central player in the neutrophil release of
      nuclear chromatin, known as neutrophil extracellular traps (NETs). NETs have been
      shown to elicit harmful effects on the host, and were recently proposed to
      promote tumor progression and spread. Here we report significant elevations of
      plasma H3Cit in patients with advanced cancer compared with age-matched healthy
      individuals. These elevations were specific to cancer patients as no increase was
      observed in severely ill and hospitalized patients with a higher non-malignant
      comorbidity. The analysis of neutrophils from cancer patients showed a higher
      proportion of neutrophils positive for intracellular H3Cit compared to severely
      ill patients. Moreover, the presence of plasma H3Cit in cancer patients strongly
      correlated with neutrophil activation markers neutrophil elastase (NE) and
      myeloperoxidase (MPO), and the inflammatory cytokines interleukin-6 and -8, known
      to induce NETosis. In addition, we show that high levels of circulating H3Cit
      strongly predicted poor clinical outcome in our cohort of cancer patients with a
      2-fold increased risk for short-term mortality. Our results also corroborate the
      association of NE, interleukin-6 and -8 with poor clinical outcome. Taken
      together, our results are the first to unveil H3Cit as a potential diagnostic and
      prognostic blood marker associated with an exacerbated inflammatory response in
      patients with advanced cancer.

PMID- 29324873
TI  - A new strength assessment to evaluate the association between muscle weakness and
      gait pathology in children with cerebral palsy.
AB  - AIM: The main goal of this validation study was to evaluate whether lower limb
      muscle weakness and plantar flexor rate of force development (RFD) related to
      altered gait parameters in children with cerebral palsy (CP), when weakness was
      assessed with maximal voluntary isometric contractions (MVICs) in a gait related
      test position. As a subgoal, we analyzed intra- and intertester reliability of
      this new strength measurement method. METHODS: Part 1 -Intra- and intertester
      reliability were determined with the intra-class correlation coefficient (ICC2,1)
      in 10 typical developing (TD) children (age: 5-15). We collected MVICs in four
      lower limb muscle groups to define maximum joint torques, as well as plantar
      flexor RFD. Part 2 -Validity of the strength assessment was explored by analyzing
      the relations of lower limb joint torques and RFD to a series of kinematic- and
      kinetic gait features, the GDI (gait deviation index), and the GDI-kinetic in 23
      children with CP (GMFCS I-II; age: 5-15) and 23 TD children (age: 5-15) with
      Spearman's rank correlation coefficients. RESULTS: Part 1 -The best reliability
      was found for the torque data (Nm), with the highest ICC2,1 (0.951) for knee
      extension strength (inter) and the lowest (0.693) for dorsiflexion strength
      (intra). For plantar flexor RFD, the most reliable window size was 300
      milliseconds (ICC2,1: 0.828 (inter) and 0.692 (intra)). Part 2 -The children with
      CP were significantly weaker than the TD children (p <0.001). Weakness of the
      dorsiflexors and plantar flexors associated with delayed and decreased knee
      flexion angle during swing, respectively. No other significant correlations were
      found. CONCLUSION: While our new strength assessment was reliable, intra-joint
      correlations between weakness, RFD, and gait deviations were low. However, we
      found inter-joint associations, reflected by a strong association between plantar
      and dorsiflexor weakness, and decreased and delayed knee flexion angle during
      swing.

PMID- 29324874
TI  - Clinical risk stratification model for advanced colorectal neoplasia in persons
      with negative fecal immunochemical test results.
AB  - OBJECTIVES: The fecal immunochemical test (FIT) has low sensitivity for detecting
      advanced colorectal neoplasia (ACRN); thus, a considerable portion of FIT
      negative persons may have ACRN. We aimed to develop a risk-scoring model for
      predicting ACRN in FIT-negative persons. MATERIALS AND METHODS: We reviewed the
      records of participants aged >=40 years who underwent a colonoscopy and FIT
      during a health check-up. We developed a risk-scoring model for predicting ACRN
      in FIT-negative persons. RESULTS: Of 11,873 FIT-negative participants, 255 (2.1%)
      had ACRN. On the basis of the multivariable logistic regression model, point
      scores were assigned as follows among FIT-negative persons: age (per year from 40
      years old), 1 point; current smoker, 10 points; overweight, 5 points; obese, 7
      points; hypertension, 6 points; old cerebrovascular attack (CVA), 15 points.
      Although the proportion of ACRN in FIT-negative persons increased as risk scores
      increased (from 0.6% in the group with 0-4 points to 8.1% in the group with 35-39
      points), it was significantly lower than that in FIT-positive persons (14.9%).
      However, there was no statistical difference between the proportion of ACRN in
      FIT-negative persons with >=40 points and in FIT-positive persons (10.5% vs.
      14.9%, P = 0.321). CONCLUSIONS: FIT-negative persons may need to undergo
      screening colonoscopy if they clinically have a high risk of ACRN. The scoring
      model based on age, smoking habits, overweight or obesity, hypertension, and old
      CVA may be useful in selecting and prioritizing FIT-negative persons for
      screening colonoscopy.

PMID- 29324875
TI  - Effect of heat input on microstructure, wear and friction behavior of (wt.-%)
      50FeCrC-20FeW-30FeB coating on AISI 1020 produced by using PTA welding.
AB  - In this study, AISI 1020 steel surface was coated in different heat inputs with
      (wt.-%) 50FeCrC-20FeW-30FeB powder mixture by using plasma transferred arc (PTA)
      welding method. The microstructure of the coated samples were investigated by
      using optical microscope (OM), scanning electron microscope (SEM), X-ray
      diffraction (XRD) and energy dispersive X-ray (EDS). The hardness was measured
      with micro hardness test device. The dry sliding wear and friction coefficient
      properties were determined using a block-on-disk type wear test device. Wear
      tests were performed at 19.62 N, 39.24 N, 58.86 N load and the sliding distance
      of 900 m. The results were shown that different microstructures formed due to the
      heat input change. The highest average micro hardness value was measured at 1217
      HV on sample coated with low heat input. It was determined that the wear
      resistance decreased with increasing heat input.

PMID- 29324876
TI  - Correction: Different transferability of incompatibility (Inc) P-7 plasmid pCAR1
      and IncP-1 plasmid pBP136 in stirring liquid conditions.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0186248.].

PMID- 29324877
TI  - Impact of extra-articular pathologies on groin pain: An arthroscopic evaluation.
AB  - PURPOSE: For patients who have anterior hip pain evaluated by Patrick's test and
      tenderness at Scarpa's triangle, we perform periarticular debridement based on
      the hypothesis that extra-articular pathologies are responsible for the hip pain.
      The purpose of this study was to categorize the endoscopic extra-articular
      findings and to evaluate the clinical significance of periarticular pathologies
      in anterior hip pain. METHODS: Arthroscopic findings of 77 patients who underwent
      periarthritic debridement were evaluated. As extra-articular pathologies,
      injuries of the direct head and reflective head of the rectus femoris muscle were
      evaluated. A thin layer of fat tissue normally exists on the anterior inferior
      iliac spine (AIIS), the attachment site of the direct head of the rectus femoris
      muscle. The macroscopic appearance of the fat pad on the AIIS was categorized as
      normal, blood vessel-rich adipose tissue or adipose tissue with fibrosis or scar
      formation and histologically confirmed. Adhesion of gluteal muscles to the joint
      capsule was also evaluated. RESULTS: Of the 77 patients, 75 had rupture of the
      direct head of the rectus femoris. In contrast, rupture of the reflective head
      was extremely rare. Seven patients had a normal fat pad on the AIIS, 11 had blood
      vessel-rich adipose tissue and 55 had adipose tissue with fibrosis. Fat tissue
      was completely replaced by fibrous scar tissue in another 4 patients. In 64
      patients, adhesion between the anterior joint capsule and gluteus muscles was
      marked. Groin pain disappeared soon after the operation even when labral tears
      were not repaired and all patients returned to daily life and sports activities
      within 2 weeks after operation. CONCLUSION: Rectus femoris tendinosis, fibrosis
      of the AIIS fat pad, and adhesion of gluteal and rectus femoris muscles are
      common extra-articular pathologies in patients with anterior hip pain. Management
      of only these lesions induces rapid relief of anterior hip pain even in the
      absence of labral tear repair. My observations suggest that it is desirable to be
      aware of the presence of periarticular pathologies as a cause of groin pain.

PMID- 29324878
TI  - The curious case of APOBEC3 activation by cancer-associated human
      papillomaviruses.

PMID- 29324879
TI  - Localized zinc distribution in shark vertebrae suggests differential deposition
      during ontogeny and across vertebral structures.
AB  - The development of shark vertebrae and the possible drivers of inter- and intra
      specific differences in vertebral structure are poorly understood. Shark
      vertebrae are used to examine life-history traits related to trophic ecology,
      movement patterns, and the management of fisheries; a better understanding of
      their development would be beneficial to many fields of research that rely on
      these calcified structures. This study used Scanning X-ray Fluorescence
      Microscopy to observe zinc distribution within vertebrae of ten shark species
      from five different orders. Zinc was mostly localised within the intermedialis
      and was generally detected at levels an order of magnitude lower in the corpus
      calcareum. In most species, zinc concentrations were higher pre-birth mark,
      indicating a high rate of pre-natal zinc deposition. These results suggest there
      are inter-specific differences in elemental deposition within vertebrae. Since
      the deposition of zinc is physiologically-driven, these differences suggest that
      the processes of growth and deposition are potentially different in the
      intermedialis and corpus calcareum, and that caution should be taken when
      extrapolating information such as annual growth bands from one structure to the
      other. Together these results suggest that the high inter-specific variation in
      vertebral zinc deposition and associated physiologies may explain the varying
      effectiveness of ageing methodologies applied to elasmobranch vertebrae.

PMID- 29324880
TI  - EDAG promotes the expansion and survival of human CD34+ cells.
AB  - EDAG is multifunctional transcriptional regulator primarily expressed in the
      linloc-kit+Sca-1+ hematopoietic stem cells (HSC) and CD34+ progenitor cells.
      Previous studies indicate that EDAG is required for maintaining hematopoietic
      lineage commitment balance. Here using ex vivo culture and HSC transplantation
      models, we report that EDAG enhances the proliferative potential of human cord
      blood CD34+ cells, increases survival, prevents cell apoptosis and promotes their
      repopulating capacity. Moreover, EDAG overexpression induces rapid entry of CD34+
      cells into the cell cycle. Gene expression profile analysis indicate that EDAG
      knockdown leads to down-regulation of various positive cell cycle regulators
      including cyclin A, B, D, and E. Together these data provides novel insights into
      EDAG in regulation of expansion and survival of human hematopoietic
      stem/progenitor cells.

PMID- 29324882
TI  - Correction: Color Doppler ultrasonography as an alternative tool for
      postoperative evaluation of collaterals after indirect revascularization surgery
      in Moyamoya disease.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0188948.].

PMID- 29324881
TI  - Genome-wide analysis and expression profiles of glyoxalase gene families in
      Chinese cabbage (Brassica rapa L).
AB  - The glyoxalase pathway is composed of glyoxalase I (GLYI) and glyoxalase II
      (GLYII) and is responsible for the detoxification of a cytotoxic metabolite
      methylglyoxal (MG) into the nontoxic S-D-lactoylglutathione. The two glyoxalase
      enzymes play a crucial role in stress tolerance in various plant species.
      Recently, the GLY gene families have well been analyzed in Arabidopsis, rice and
      soybean, however, little is known about them in Chinese cabbage (Brassica rapa).
      Here, 16 BrGLYI and 15 BrGLYII genes were identified in the B. rapa genome, and
      the BrGLYI and BrGLYII proteins were both clustered into five subfamilies. The
      classifications, chromosomal distributions, gene duplications, exon-intron
      structures, localizations, conserved motifs and promoter cis-elements were also
      predicted and analyzed. In addition, the expression pattern of these genes in
      different tissues and their response to biotic and abiotic stresses were analyzed
      using publicly available data and a quantitative real-time PCR analysis (RT
      qPCR). The results indicated that the expression profiles of BrGLY genes varied
      among different tissues. Notably, a number of BrGLY genes showed responses to
      biotic and abiotic stress treatments, including Plasmodiophora brassicae
      infection and various heavy metal stresses. Taken together, this study identifies
      BrGLYI and BrGLYII gene families in B. rapa and offers insight into their roles
      in plant development and stress resistance, especially in heavy metal stress
      tolerance and pathogen resistance.

PMID- 29324883
TI  - MASP-1 of the complement system enhances clot formation in a microvascular whole
      blood flow model.
AB  - The complement and coagulation systems closely interact with each other. These
      interactions are believed to contribute to the proinflammatory and prothrombotic
      environment involved in the development of thrombotic complications in many
      diseases. Complement MASP-1 (mannan-binding lectin-associated serine protease-1)
      activates coagulation factors and promotes clot formation. However, this was
      mainly shown in purified or plasma-based static systems. Here we describe the
      role of MASP-1 and complement activation in fibrin clot formation in a
      microvascular, whole blood flow model. This microfluidic system simulates blood
      flow through microvessels at physiological flow and shear rates and represents
      the closest model system to human physiology so far. It features parallel
      microchannels cultured with endothelial cells in a transparent microfluidic chip
      allowing real-time evaluation of clot formation by confocal microscopy. To test
      their effects on clot formation, we added the following activators or inhibitors
      (individually or in combination) to whole blood and performed perfusion
      experiments: rMASP-1cf (recombinant active form of MASP-1), complement activator
      zymosan, selective MASP-1 inhibitor SGMI-1 (based on the Schistocerca gregaria
      protease inhibitor scaffold), classical pathway inhibitor rSALO (recombinant
      salivary anti-complement from Lutzomyia longipalpis). Addition of rMASP-1cf
      resulted in accelerated fibrin clot formation while addition of SGMI-1 delayed
      it. Complement activation by zymosan led to increased clot formation and this
      effect was partially reversed by addition of rSALO and almost abolished in
      combination with SGMI-1. We show for the first time a strong influence of MASP-1,
      complement activation and pathway-specific inhibition on coagulation in a
      microvascular flow system that is closest to human physiology, further
      underpinning the in vivo relevance of coagulation and complement interactions.

PMID- 29324885
TI  - Correction: Expected population weight and diabetes impact of the 1-peso-per
      litre tax to sugar sweetened beverages in Mexico.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0176336.].

PMID- 29324884
TI  - A cross sectional study on Dutch layer farms to investigate the prevalence and
      potential risk factors for different Chlamydia species.
AB  - In poultry several Chlamydia species have been detected, but Chlamydia psittaci
      and Chlamydia gallinacea appear to be most prevalent and important. Chlamydia
      psittaci is a well-known zoonosis and is considered to be a pathogen of poultry.
      Chlamydia gallinacea has been described more recently. Its avian pathogenicity
      and zoonotic potential have to be further elucidated. Within the Netherlands no
      data were available on the presence of Chlamydia on poultry farms. As part of a
      surveillance programme for zoonotic pathogens in farm animals, we investigated
      pooled faecal samples from 151 randomly selected layer farms. On a voluntary
      base, 69 farmers, family members or farm workers from these 151 farms submitted a
      throat swab. All samples were tested with a generic 23S Chlamydiaceae PCR
      followed by a species specific PCR for C. avium, C. gallinacea and C. psittaci.
      C. avium and psittaci DNA was not detected at any of the farms. At 71 farms the
      positive result could be confirmed as C. gallinacea. Variables significantly
      associated with the presence of C. gallinacea in a final multivariable model were
      'age of hens,' 'use of bedding material' and 'the presence of horses.' The
      presence of C. gallinacea was associated with neither clinical signs, varying
      from respiratory symptoms, nasal and ocular discharges to diarrhoea, nor with a
      higher mortality rate the day before the visit. All throat swabs from farmers,
      family members or farm workers tested negative for Chlamydia DNA, giving no
      further indication for possible bird-to-human (or human-to-bird) transmission.

PMID- 29324886
TI  - Changes in network connectivity during motor imagery and execution.
AB  - BACKGROUND: Recent studies of functional or effective connectivity in the brain
      have reported that motor-related brain regions were activated during motor
      execution and motor imagery, but the relationship between motor and cognitive
      areas has not yet been completely understood. The objectives of our study were to
      analyze the effective connectivity between motor and cognitive networks in order
      to define network dynamics during motor execution and motor imagery in healthy
      individuals. Second, we analyzed the differences in effective connectivity
      between correct and incorrect responses during motor execution and imagery using
      dynamic causal modeling (DCM) of electroencephalography (EEG) data. METHOD:
      Twenty healthy subjects performed a sequence of finger tapping trials using
      either motor execution or motor imagery, and the performances were recorded.
      Changes in effective connectivity between the primary motor cortex (M1),
      supplementary motor area (SMA), premotor cortex (PMC), and dorsolateral
      prefrontal cortex (DLPFC) were estimated using dynamic causal modeling. Bayesian
      model averaging with family-level inference and fixed-effects analysis was
      applied to determine the most likely connectivity model for these regions.
      RESULTS: Motor execution and imagery showed inputs to distinct brain regions, the
      premotor cortex and the supplementary motor area, respectively. During motor
      execution, the coupling strength of a feedforward network from the DLPFC to the
      PMC was greater than that during motor imagery. During motor imagery, the
      coupling strengths of a feedforward network from the PMC to the SMA and of a
      feedback network from M1 to the PMC were higher than that during motor execution.
      In imagined movement, although there were connectivity differences between
      correct and incorrect task responses, each motor imagery task that included
      correct and incorrect responses showed similar network connectivity
      characteristics. Correct motor imagery responses showed connectivity from the PMC
      to the DLPFC, while the incorrect responses had characteristic connectivity from
      the SMA to the DLPFC. CONCLUSIONS: These findings provide an understanding of
      effective connectivity between motor and cognitive areas during motor execution
      and imagery as well as the basis for future connectivity studies for patients
      with stroke.

PMID- 29324887
TI  - The "Tracked Roaming Transect" and distance sampling methods increase the
      efficiency of underwater visual censuses.
AB  - Underwater visual census (UVC) is the most common approach for estimating
      diversity, abundance and size of reef fishes in shallow and clear waters.
      Abundance estimation through UVC is particularly problematic in species occurring
      at low densities and/or highly aggregated because of their high variability at
      both spatial and temporal scales. The statistical power of experiments involving
      UVC techniques may be increased by augmenting the number of replicates or the
      area surveyed. In this work we present and test the efficiency of an UVC method
      based on diver towed GPS, the Tracked Roaming Transect (TRT), designed to
      maximize transect length (and thus the surveyed area) with respect to diving time
      invested in monitoring, as compared to Conventional Strip Transects (CST).
      Additionally, we analyze the effect of increasing transect width and length on
      the precision of density estimates by comparing TRT vs. CST methods using
      different fixed widths of 6 and 20 m (FW3 and FW10, respectively) and the
      Distance Sampling (DS) method, in which perpendicular distance of each fish or
      group of fishes to the transect line is estimated by divers up to 20 m from the
      transect line. The TRT was 74% more time and cost efficient than the CST (all
      transect widths considered together) and, for a given time, the use of TRT and/or
      increasing the transect width increased the precision of density estimates. In
      addition, since with the DS method distances of fishes to the transect line have
      to be estimated, and not measured directly as in terrestrial environments, errors
      in estimations of perpendicular distances can seriously affect DS density
      estimations. To assess the occurrence of distance estimation errors and their
      dependence on the observer's experience, a field experiment using wooden fish
      models was performed. We tested the precision and accuracy of density estimators
      based on fixed widths and the DS method. The accuracy of the estimates was
      measured comparing the actual total abundance with those estimated by divers
      using FW3, FW10, and DS estimators. Density estimates differed by 13% (range 0.1
      31%) from the actual values (average = 13.09%; median = 14.16%). Based on our
      results we encourage the use of the Tracked Roaming Transect with Distance
      Sampling (TRT+DS) method for improving density estimates of species occurring at
      low densities and/or highly aggregated, as well as for exploratory rapid
      assessment surveys in which divers could gather spatial ecological and ecosystem
      information on large areas during UVC.

PMID- 29324889
TI  - Correction: Impact of Heat Stress on Cellular and Transcriptional Adaptation of
      Mammary Epithelial Cells in Riverine Buffalo (Bubalus Bubalis).
AB  - [This corrects the article DOI: 10.1371/journal.pone.0157237.].

PMID- 29324888
TI  - Transcription factor Runx1 is pro-neurogenic in adult hippocampal precursor
      cells.
AB  - Transcription factor Runx1 (Runt Related Transcription Factor 1), plays an
      important role in the differentiation of hematopoetic stem cells, angiogenesis
      and the development of nociceptive neurons. These known functions have in common
      that they relate to lineage decisions. We thus asked whether such role might also
      be found for Runx1 in adult hippocampal neurogenesis as a process, in which such
      decisions have to be regulated lifelong. Runx1 shows a widespread low expression
      in the adult mouse brain, not particularly prominent in the hippocampus and the
      resident neural precursor cells. Isoforms 1 and 2 of Runx1 (but not 3 to 5)
      driven by the proximal promoter were expressed in hippocampal precursor cells ex
      vivo, albeit again at very low levels, and were markedly increased after
      stimulation with TGF-beta1. Under differentiation conditions (withdrawal of
      growth factors) Runx1 became down-regulated. Overexpression of Runx1 in vitro
      reduced proliferation, increased survival of precursor cells by reducing
      apoptosis, and increased neuronal differentiation, while slightly reducing
      dendritic morphology and complexity. Transfection with dominant-negative Runx1 in
      hippocampal precursor cells in vitro did not result in differences in
      neurogenesis. Hippocampal expression of Runx1 correlated with adult neurogenesis
      (precursor cell proliferation) across BXD recombinant strains of mice and
      covarying transcripts enriched in the GO categories "neural precursor cell
      proliferation" and "neuron differentiation". Runx1 is thus a plausible candidate
      gene to be involved in regulating initial differentiation-related steps of adult
      neurogenesis. It seems, however, that the relative contribution of Runx1 to such
      effect is complementary and will explain only small parts of the cell-autonomous
      pro-differentiation effect.

PMID- 29324890
TI  - Correction: Behavioral and Neural Correlates of Executive Functioning in
      Musicians and Non-Musicians.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0099868.].

PMID- 29324891
TI  - Correction: Effects of Spirulina on the functions and redox status of auditory
      system in senescence-accelerated prone-8 mice.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0178916.].

PMID- 29324892
TI  - Genetic factors have a major effect on growth, number of vertebrae and otolith
      shape in Atlantic herring (Clupea harengus).
AB  - Atlantic herring, Clupea harengus, have complex population structures. Mixing of
      populations is known, but the extent of connectivity is still unclear. Phenotypic
      plasticity results in divergent phenotypes in response to environmental factors.
      A marked salinity gradient occurs from Atlantic Ocean (salinity 35) into the
      Baltic Sea (salinity range 2-12). Herring from both habitats display phenotypic
      and genetic variability. To explore how genetic factors and salinity influence
      phenotypic traits like growth, number of vertebrae and otolith shape an
      experimental population consisting of Atlantic purebreds and Atlantic/Baltic F1
      hybrids were incubated and co-reared at two different salinities, 16 and 35, for
      three years. The F1-generation was repeatedly sampled to evaluate temporal
      variation. A von Bertalanffy growth model indicated that reared Atlantic
      purebreds had a higher maximum length (26.2 cm) than Atlantic/Baltic hybrids
      (24.8 cm) at salinity 35, but not at salinity 16 (25.0 and 24.8 cm,
      respectively). In contrast, Atlantic/Baltic hybrids achieved larger size-at-age
      than the wild caught Baltic parental group. Mean vertebral counts and otolith
      aspect ratios were higher for reared Atlantic purebreds than Atlantic/Baltic
      hybrids, consistent with the differences between parental groups. There were no
      significant differences in vertebral counts and otolith aspect ratios between
      herring with the same genotype but raised in different salinities. A Canonical
      Analysis of Principal Coordinates was applied to analyze the variation in wavelet
      coefficients that described otolith shape. The first discriminating axis
      identified the differences between Atlantic purebreds and Atlantic/Baltic
      hybrids, while the second axis represented salinity differences. Assigning
      otoliths based on genetic groups (Atlantic purebreds vs. Atlantic/Baltic hybrids)
      yielded higher classification success (~90%) than based on salinities (16 vs. 35;
      ~60%). Our results demonstrate that otolith shape and vertebral counts have a
      significant genetic component and are therefore useful for studies on population
      dynamics and connectivity.

PMID- 29324893
TI  - Comparative transcriptome analysis reveals significant metabolic alterations in
      eri-silkworm (Samia cynthia ricini) haemolymph in response to 1-deoxynojirimycin.
AB  - Samia cynthia ricini (Lepidoptera: Saturniidae) is an important commercial silk
      producing insect; however, in contrast to the silkworm, mulberry leaves are toxic
      to this insect because the leaves contain the component 1-deoxynojirimycin (DNJ).
      A transcriptomic analysis of eri-silkworm haemolymph was conducted to examine the
      genes related to different metabolic pathways and to elucidate the molecular
      mechanism underlying eri-silkworm haemolymph responses to DNJ. Eight hundred
      sixty-five differentially expressed genes (DEGs) were identified, among which 577
      DEGs were up-regulated and 288 DEGs were down-regulated in the 2% DNJ group
      compared to control (ddH2O) after 12h. Based on the results of the functional
      analysis, these DEGs were associated with ribosomes, glycolysis, N-glycan
      biosynthesis, and oxidative phosphorylation. In particular, according to the KEGG
      analysis, 138 DEGs were involved in energy metabolism, glycometabolism and lipid
      metabolism, and the changes in the expression of nine DEGs were confirmed by
      reverse transcription quantitative PCR (RT-qPCR). Thus, DNJ induced significant
      metabolic alterations in eri-silkworm haemolymph. These results will lay the
      foundation for research into the toxic effects of DNJ on eri-silkworm as a model
      and provide a reference for the exploitation of new drugs in humans.

PMID- 29324894
TI  - The obesity epidemic and rising diabetes incidence in a low-income racially
      diverse southern US cohort.
AB  - BACKGROUND: Obesity is known to be a major risk factor for diabetes, but the
      magnitude of risk and variation between blacks and whites are less well
      documented in populations heavily affected by obesity. Herein we assess rates and
      risks of incident diabetes in a diverse southern population where obesity is
      common. METHODS: A total of 24,000 black and 14,064 white adults aged 40-79 in
      the Southern Community Cohort Study with no self-reported diabetes at study
      enrollment during 2002-2009 was followed for up to 10 (median 4.5) years.
      Incidence rates, odds ratios (OR) and accompanying 95% confidence intervals (CI)
      for medication-treated incident diabetes were determined according to body mass
      index (BMI) and other characteristics, including tobacco and alcohol consumption,
      healthy eating and physical activity indices, and socioeconomic status (SES).
      RESULTS: Risk of incident diabetes rose monotonically with increasing BMI, but
      the trends differed between blacks and whites (pinteraction < .0001). Adjusted
      ORs (CIs) for diabetes among those with BMI>=40 vs 20-25 kg/m2 were 11.9 (8.4
      16.8) for whites and 4.0 (3.3-4.8) for blacks. Diabetes incidence was more than
      twice as high among blacks than whites of normal BMI, but the racial difference
      became attenuated as BMI rose, with estimated 5-year probabilities of developing
      diabetes approaching 20% for both blacks and whites with BMI>=40 kg/m2. Diabetes
      risk was also associated with low SES, significantly (pinteraction<=.02) more so
      for whites, current cigarette smoking, and lower healthy eating and physical
      activity indices, although high BMI remained the predominant risk factor among
      both blacks and whites. From baseline prevalence and 20-year projections of the
      incidence trends, we estimate that the large majority of surviving cohort
      participants with BMI>=40 kg/m2 will be diagnosed with diabetes. CONCLUSIONS:
      Even using conservative criteria to ascertain diabetes incidence (i.e., requiring
      diabetes medication use and ignoring undiagnosed cases), rates of obesity
      associated diabetes were exceptionally high in this low-income adult population.
      The findings indicate that effective strategies to halt the rising prevalence of
      obesity are needed to avoid substantial increases in diabetes in coming years.

PMID- 29324895
TI  - Continental synchronicity of human influenza virus epidemics despite climatic
      variation.
AB  - The factors that determine the pattern and rate of spread of influenza virus at a
      continental-scale are uncertain. Although recent work suggests that influenza
      epidemics in the United States exhibit a strong geographical correlation, the
      spatiotemporal dynamics of influenza in Australia, a country and continent of
      approximately similar size and climate complexity but with a far smaller
      population, are not known. Using a unique combination of large-scale laboratory
      confirmed influenza surveillance comprising >450,000 entries and genomic sequence
      data we determined the local-level spatial diffusion of this important human
      pathogen nationwide in Australia. We used laboratory-confirmed influenza data to
      characterize the spread of influenza virus across Australia during 2007-2016. The
      onset of established epidemics varied across seasons, with highly synchronized
      epidemics coinciding with the emergence of antigenically distinct viruses,
      particularly during the 2009 A/H1N1 pandemic. The onset of epidemics was largely
      synchronized between the most populous cities, even those separated by distances
      of >3000 km and those that experience vastly diverse climates. In addition, by
      analyzing global phylogeographic patterns we show that the synchronized
      dissemination of influenza across Australian cities involved multiple
      introductions from the global influenza population, coupled with strong domestic
      connectivity, rather than through the distinct radial patterns of geographic
      dispersal that are driven by work-flow transmission as observed in the United
      States. In addition, by comparing the spatial structure of influenza A and B, we
      found that these viruses tended to occupy different geographic regions, and peak
      in different seasons, perhaps indicative of moderate cross-protective immunity or
      viral interference effects. The highly synchronized outbreaks of influenza virus
      at a continental-scale revealed here highlight the importance of coordinated
      public health responses in the event of the emergence of a novel, human-to-human
      transmissible, virus.

PMID- 29324896
TI  - Correlation of the anterior ocular segment biometry with HbA1c level in type 2
      diabetes mellitus patients.
AB  - OBJECTIVES: To compare the anterior ocular segment biometry among Type 2 diabetes
      mellitus (DM) with no diabetic retinopathy (DR) and non-proliferative diabetic
      retinopathy (NPDR), and to evaluate the correlation of anterior ocular segment
      biometry with HbA1c level. METHODS: A cross-sectional study was conducted in
      Hospital Universiti Sains Malaysia, Kelantan from November 2013 till May 2016
      among Type 2 DM patients (DM with no DR and DM with NPDR). The patients were
      evaluated for anterior ocular segment biometry [central corneal thickness (CCT),
      anterior chamber width (ACW), angle opening distance (AOD) and anterior chamber
      angle (ACA)] by using Anterior Segment Optical Coherence Tomography (AS-OCT).
      Three ml venous blood was taken for the measurement of HbA1c. RESULTS: A total of
      150 patients were included in this study (DM with no DR: 50 patients, DM with
      NPDR: 50 patients, non DM: 50 patients as a control group). The mean CCT and ACW
      showed significant difference among the three groups (p < 0.001 and p = 0.015
      respectively). Based on post hoc result, there were significant mean difference
      of CCT between non DM and DM with NPDR (mean difference 36.14 MUm, p < 0.001) and
      also between non DM and DM with no DR (mean difference 31.48 MUm, p = 0.003). The
      ACW was significantly narrower in DM with NPDR (11.39 mm SD 0.62) compared to DM
      with no DR (11.76 mm SD 0.53) (p = 0.012). There were no significant correlation
      between HbA1c and all the anterior ocular segment biometry. CONCLUSION: Diabetic
      patients have significantly thicker CCT regardless of retinopathy status whereas
      ACW was significantly narrower in DM with NPDR group compared to DM with no DR.
      There was no significant correlations between HbA1c and all anterior ocular
      segment biometry in diabetic patients regardless of DR status.

PMID- 29324897
TI  - Serum galactose-deficient-IgA1 and IgG autoantibodies correlate in patients with
      IgA nephropathy.
AB  - IgA nephropathy is an autoimmune disease characterized by IgA1-containing
      glomerular immune deposits. We previously proposed a multi-hit pathogenesis model
      in which patients with IgA nephropathy have elevated levels of circulatory IgA1
      with some O-glycans deficient in galactose (Gd-IgA1, autoantigen). Gd-IgA1 is
      recognized by anti-glycan IgG and/or IgA autoantibodies, resulting in formation
      of pathogenic immune complexes. Some of these immune complexes deposit in the
      kidney, activate mesangial cells, and incite glomerular injury leading to
      clinical presentation of IgA nephropathy. Several studies have demonstrated that
      elevated circulatory levels of either Gd-IgA1 or the corresponding autoantibodies
      predict progressive loss of renal clearance function. In this study we assessed a
      possible association between serum levels of Gd-IgA1 and IgG or IgA
      autoantibodies specific for Gd-IgA1 in serum samples from 135 patients with
      biopsy-proven IgA nephropathy, 76 patients with other renal diseases, and 106
      healthy controls. Our analyses revealed a correlation between the concentrations
      of the autoantigen and the corresponding IgG autoantibodies in sera of patients
      with IgA nephropathy, but not of disease or healthy controls. Moreover, our data
      suggest that IgG is the predominant isotype of Gd-IgA1-specific autoantibodies in
      IgA nephropathy. This work highlights the importance of both initial hits in the
      pathogenesis of IgA nephropathy.

PMID- 29324898
TI  - The etomidate analog ET-26 HCl retains superior myocardial performance:
      Comparisons with etomidate in vivo and in vitro.
AB  - OBJECTIVE: (R)-2-methoxyethyl1-(1-phenylethyl)-1H-imidazole-5-carboxylate
      hydrochloride (ET-26 HCl) is a novel etomidate analogue. The purpose of this
      study was to characterize whether ET-26 HCl could retain the superior myocardial
      performance of etomidate in vivo and in vitro. METHODS: In vivo, the influence of
      ET-26 HCl and etomidate on the cardiac function of dogs was confirmed using
      echocardiography and electrocardiogram. In vitro, a Langendorff preparation was
      used to examine direct myocardial performance in isolated rat hearts, and a whole
      cell patch-clamp technique was used to study effects on the human ether-a-go-go
      related gene (hERG) channel. RESULTS: In vivo, after a single bolus
      administration of ET-26 HCl or etomidate, no significant difference in
      echocardiography and electrocardiogram parameters was observed. No arrhythmia
      occurred and no QT interval prolongation happened during the study period. In the
      in vitro Langendorff preparation, none of the cardiac parameters were abnormal,
      and the hERG recordings showed that ET-26 HCl and etomidate inhibited the tail
      current of the hERG in a concentration-dependent manner with an IC50 of 742.51
      MUM and 263.60 MUM, respectively. CONCLUSIONS: In conclusion, through an in vivo
      experiment and a whole organ preparation, the current study found that ET-26 HCl
      can maintain a myocardial performance that is similar to that of etomidate. In
      addition, the electrophysiology study indicated that ET-26 HCl and etomidate
      inhibited the hERG at a supra-therapeutic concentration.

PMID- 29324899
TI  - The effects of high dose of two manganese supplements (organic and inorganic) on
      the rumen microbial ecosystem.
AB  - Little is known about the effects of the high dose and types of manganese
      supplements on rumen environment at manganese intake level close above the limit
      of 150 mg/kg of dry feed matter. The effects of high dose of two manganese
      supplements (organic and inorganic) on rumen microbial ecosystem after four
      months of treatment of 18 lambs divided into three treatment groups were studied.
      We examined the enzyme activities (alpha-amylase, xylanase, and carboxymethyl
      cellulase), total and differential microscopic counts of rumen ciliates, total
      microscopic counts of bacteria, and fingerprinting pattern of the eubacterial and
      ciliates population analyzed by PCR-DGGE. Lambs were fed a basal diet with a
      basal Mn content (34.3 mg/kg dry matter; control) and supplemented either with
      inorganic manganous sulfate or organic Mn-chelate hydrate (daily 182.7, 184 mg/kg
      dry matter of feed, respectively). Basal diet, offered twice daily, consisted of
      ground barley and hay (268 and 732 g/kg dry matter per animal and day). The
      rumens of the lambs harbored ciliates of the genera of Entodinium, Epidinium,
      Diplodinium, Eudiplodinium, Dasytricha, and Isotricha. No significant differences
      between treatment groups were observed in the total ciliate number, the number of
      ciliates at the genus level, as well as the total number of bacteria. Organic Mn
      did decrease the species richness and diversity of the eubacterial population
      examined by PCR-DGGE. No effects of type of Mn supplement on the enzyme
      activities were observed. In comparison to the control, alpha-amylase specific
      activities were decreased and carboxymethyl-cellulase specific activities were
      increased by the Mn supplements. Xylanase activities were not influenced. In
      conclusion, our results suggested that the intake of tested inorganic and organic
      manganese supplements in excess may affect the specific groups of eubacteria.
      More studies on intake of Mn supplements at a level close to the limit can reveal
      if the changes in microbial population impact remarkably the other rumen
      enzymatic activities.

PMID- 29324900
TI  - Internal carotid artery stenosis: A novel surgical model for moyamoya syndrome.
AB  - Moyamoya is a cerebrovascular disorder characterized by progressive stenosis of
      the intracranial internal carotid arteries. There are two forms: Disease and
      Syndrome, with each characterized by the sub-population it affects. Moyamoya
      syndrome (MMS) is more prominent in adults in their 20's-40's, and is often
      associated with autoimmune diseases. Currently, there are no surgical models for
      inducing moyamoya syndrome, so our aim was to develop a new animal model to study
      this relatively unknown cerebrovascular disease. Here, we demonstrate a new
      surgical technique termed internal carotid artery stenosis (ICAS), to mimic MMS
      using micro-coils on the proximal ICA. We tested for Moyamoya-like vasculopathies
      by fluorescently labelling the mouse cerebrovasculature with Di I for
      visualization and analysis of vessel diameter at the distal ICA and anastomoses
      on the cortical surface. Results show a significant narrowing of the distal ICA
      and anterior cerebral artery (ACA) in the Circle of Willis, as observed in
      humans. There is also a significant decrease in the number of anastomoses between
      the middle cerebral artery (MCA) and the ACA in the watershed region of the
      cortex. While further characterization is needed, this ICAS model can be applied
      to transgenic mice displaying co-morbidities as observed within the Moyamoya
      syndrome population, allowing a better understanding of the disease and
      development of novel treatments.

PMID- 29324901
TI  - The relationship between species richness and aboveground biomass in a primary
      Pinus kesiya forest of Yunnan, southwestern China.
AB  - The relationship between biodiversity and biomass is an essential element of the
      natural ecosystem functioning. Our research aims at assessing the effects of
      species richness on the aboveground biomass and the ecological driver of this
      relationship in a primary Pinus kesiya forest. We sampled 112 plots of the
      primary P. kesiya forests in Yunnan Province. The general linear model and the
      structural equation model were used to estimate relative effects of multivariate
      factors among aboveground biomass, species richness and the other explanatory
      variables, including climate moisture index, soil nutrient regime and stand age.
      We found a positive linear regression relationship between the species richness
      and aboveground biomass using ordinary least squares regressions. The species
      richness and soil nutrient regime had no direct significant effect on aboveground
      biomass. However, the climate moisture index and stand age had direct effects on
      aboveground biomass. The climate moisture index could be a better link to mediate
      the relationship between species richness and aboveground biomass. The species
      richness affected aboveground biomass which was mediated by the climate moisture
      index. Stand age had direct and indirect effects on aboveground biomass through
      the climate moisture index. Our results revealed that climate moisture index had
      a positive feedback in the relationship between species richness and aboveground
      biomass, which played an important role in a link between biodiversity
      maintenance and ecosystem functioning. Meanwhile, climate moisture index not only
      affected positively on aboveground biomass, but also indirectly through species
      richness. The information would be helpful in understanding the biodiversity
      aboveground biomass relationship of a primary P. kesiya forest and for forest
      management.

PMID- 29324902
TI  - Potential impact of neonicotinoid use on Northern bobwhite (Colinus virginianus)
      in Texas: A historical analysis.
AB  - The widespread use of neonicotinoid insecticides in recent years has led to
      increasing environmental concern, including impacts to avian populations. In
      Texas and across their range, Northern bobwhite (Colinus virginianus) habitat
      frequently overlaps cultivated cropland protected by neonicotinoids. To address
      the effects of neonicotinoid use on bobwhites in Texas, we conducted a historical
      analysis from 1978-2012 in Texas' ecological regions using quail count data
      collected from North American Breeding Bird Survey and Texas Parks and Wildlife
      Department, and neonicotinoid use data from the U.S. Geological Survey. We
      considered bobwhite abundance, neonicotinoid use, climate, and land-use variables
      in our analysis. Neonicotinoid use was significantly (p<0.05) negatively
      associated with bobwhite abundance in the High Plains, Rolling Plains, Gulf Coast
      Prairies & Marshes, Edwards Plateau, and South Texas Plains ecological regions in
      the time periods following neonicotinoid introduction (1994-2003) or after their
      widespread use (2004-2012). Our analyses suggest that the use of neonicotinoid
      insecticides may negatively affect bobwhite populations in crop-producing regions
      of Texas.

PMID- 29324903
TI  - Korean survey data reveals an association of chronic laryngitis with tinnitus in
      men.
AB  - The association between chronic laryngitis and tinnitus is not a well-studied
      topic, unlike the association of these two conditions with many other disorders.
      Cross-sectional data of 11,347 adults (males: 4,934; females: 6,413), who
      completed the Korea National Health and Nutrition Examination Survey (KNHANES)
      from 2010 to 2012 were used to investigate this association. Lifestyle patterns,
      including smoking and alcohol habits, regular exercise, physical and mental
      health status, socioeconomic status, nutritional status, and other chronic
      diseases, were analyzed. Chronic laryngitis and tinnitus were diagnosed by field
      survey teams, which included otolaryngologists, who conducted chronic disease
      surveillance using a health status interview, a nutritional status questionnaire,
      and a physical examination. Chronic laryngitis was significantly associated with
      age, education beyond high school, depressed mood, voice change, metabolic
      syndrome, and tinnitus in men. In women, chronic laryngitis was associated with
      body mass index and diabetes mellitus. Chronic laryngitis in men was
      significantly associated with tinnitus (odds ratio 1.671, [95% confidence
      interval: 1.167-2.393]) after adjusting for age, body mass index, smoking status,
      alcohol intake, regular exercise, metabolic syndrome, education beyond high
      school, and depressed mood. Additionally, the prevalence of chronic laryngitis
      increased with increasing severity of tinnitus in men alone (P = 0.002). The
      study revealed a significant association between chronic laryngitis and tinnitus.

PMID- 29324904
TI  - Prohibitin plays a critical role in Enterovirus 71 neuropathogenesis.
AB  - A close relative of poliovirus, enterovirus 71 (EV71) is regarded as an important
      neurotropic virus of serious public health concern. EV71 causes Hand, Foot and
      Mouth Disease and has been associated with neurological complications in young
      children. Our limited understanding of the mechanisms involved in its
      neuropathogenesis has hampered the development of effective therapeutic options.
      Here, using a two-dimensional proteomics approach combined with mass
      spectrometry, we have identified a unique panel of host proteins that were
      differentially and dynamically modulated during EV71 infection of motor-neuron
      NSC-34 cells, which are found at the neuromuscular junctions where EV71 is
      believed to enter the central nervous system. Meta-analysis with previously
      published proteomics studies in neuroblastoma or muscle cell lines revealed
      minimal overlapping which suggests unique host-pathogen interactions in NSC-34
      cells. Among the candidate proteins, we focused our attention on prohibitin
      (PHB), a protein that is involved in multiple cellular functions and the target
      of anti-cancer drug Rocaglamide (Roc-A). We demonstrated that cell surface
      expressed PHB is involved in EV71 entry into neuronal cells specifically, while
      membrane-bound mitochondrial PHB associates with the virus replication complex
      and facilitates viral replication. Furthermore, Roc-A treatment of EV71-infected
      neuronal cells reduced significantly virus yields. However, the inhibitory effect
      of Roc-A on PHB in NSC-34 cells was not through blocking the CRAF/MEK/ERK pathway
      as previously reported. Instead, Roc-A treated NSC-34 cells had lower
      mitochondria-associated PHB and lower ATP levels that correlated with impaired
      mitochondria integrity. In vivo, EV71-infected mice treated with Roc-A survived
      longer than the vehicle-treated animals and had significantly lower virus loads
      in their spinal cord and brain, whereas virus titers in their limb muscles were
      comparable to controls. Together, this study uncovers PHB as the first host
      factor that is specifically involved in EV71 neuropathogenesis and a potential
      drug target to limit neurological complications.

PMID- 29324905
TI  - Strains of bacterial species induce a greatly varied acute adaptive immune
      response: The contribution of the accessory genome.
AB  - A fundamental question in human susceptibility to bacterial infections is to what
      extent variability is a function of differences in the pathogen species or in
      individual humans. To focus on the pathogen species, we compared in the same
      individual the human adaptive T and B cell immune response to multiple strains of
      two major human pathogens, Staphylococcus aureus and Streptococcus pyogenes. We
      found wide variability in the acute adaptive immune response induced by various
      strains of a species, with a unique combination of activation within the two arms
      of the adaptive response. Further, this was also accompanied by a dramatic
      difference in the intensity of the specific protective T helper (Th) response.
      Importantly, the same immune response differences induced by the individual
      strains were maintained across multiple healthy human donors. A comparison of
      isogenic phage KO strains, demonstrated that of the pangenome, prophages were the
      major contributor to inter-strain immune heterogeneity, as the T cell response to
      the remaining "core genome" was noticeably blunted. Therefore, these findings
      extend and modify the notion of an adaptive response to a pathogenic bacterium,
      by implying that the adaptive immune response signature of a bacterial species
      should be defined either per strain or alternatively to the species' 'core
      genome', common to all of its strains. Further, our results demonstrate that the
      acquired immune response variation is as wide among different strains within a
      single pathogenic species as it is among different humans, and therefore may
      explain in part the clinical heterogeneity observed in patients infected with the
      same species.

PMID- 29324907
TI  - Correction: ANK1 is up-regulated in laser captured microglia in Alzheimer's
      brain; the importance of addressing cellular heterogeneity.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0177814.].

PMID- 29324906
TI  - Habits of a highly successful cereal killer, Striga.

PMID- 29324909
TI  - Effect of hypoparathyroid on bone mineral density of lumber spine in
      postmenopausal women with differentiated thyroid cancinoma.
AB  - OBJECTIVE: To investigate the effect of hypoparathyroid on bone mineral density
      in postmenopausal women with differentiated thyroid carcinoma (DTC). SUBJECT AND
      METHODS: Postmenopausal women with postoperative DTC, and undergoing thyroid
      residual ablation or for metastases treatment were collected and followed for two
      years. They were divided into hypoparathyroid group (PTH<15pg/mL) and a normal
      cognitive group (PTH>15pg/mL). Bone mineral density (BMD) at the lumbar spine was
      analyzed using dual-energy X-ray absorptiometry (DXA) at baseline, 6, 12 and 24
      months. All patients had calcium and active vitamin D supplementation. RESULTS:
      The thyroid cancers included 211 papillary carcinomas, 14 follicular carcinomas.
      The majority of them were retired from previous work (157/225, 70%). There were
      45 DTC patients in hypoparathyroid group and 180 patients in PTH normal group
      (postmenopausal controls). They are comparable in age, TSH suppression, BMD at
      baseline. There is no significant difference in BMD of lumbar spine between
      hypoparathyroid group and postmenopausal controls at baseline 6, 12 and 24 months
      follow-up which were1.03+/-0.14 and 1.04+/-0.18 (t=0.4, P=0.69), 1.04+/-0.13 and
      1.01+/-0.19 (t=1.25, P=0.21), 1.06+/-0.15 and 1.02+/-0.16 (t=1.16, P=0.26),
      1.06+/-0.21 and 1.01+/-0.17 (t=0.93, P=0.29), respectively. Areal BMD was
      increased by 2.9% in hypoparathyroid group in the lumbar spine at 12 and 24
      months follow-up, while decrease of 2.9% in postmenopausal controls. No increase
      in BMD at lumbar spine was found in postmenopausal controls. CONCLUSION:
      Transient hypoparathyroid increased BMD at lumbar spine by DXA in postmenopausal
      DTC patients compared to postmenopausal controls.

PMID- 29324908
TI  - Peripheral quantitative computed tomography detects differences at the radius in
      prepubertal children with cystic fibrosis compared to healthy controls.
AB  - INTRODUCTION: In 2015, 11.9% of people with cystic fibrosis (CF) in the United
      States had osteopenia, 5.1% osteoporosis, and 0.3% experienced a fracture.
      Screening for CF-related bone disease starts in childhood, and dual energy x-ray
      absorptiometry (DXA) is the recommended method. It is unknown whether peripheral
      quantitative computed tomography (pQCT) can detect deficits earlier than DXA.
      This study compared pQCT and DXA scans in a group of pre-pubertal children with
      CF and healthy controls. METHODS: This was a cross-sectional study of children at
      Tanner stage 1. A pQCT scan of the radius at proximal and distal sites was
      performed plus a total body DXA scan. Serum C-reactive protein, interleukin-6 and
      tumor necrosis factor-alpha were also measured. RESULTS: A total of 34 subjects
      completed the study; 14 with CF and 20 controls. At the distal radius, pQCT
      showed a lower total bone mineral density (BMD) Z-score for the CF group (P =
      0.01 and P = 0.03 for 2 different reference databases) compared to controls. At
      the proximal site, the polar strength-strain index was lower in the CF group (P =
      0.017). Finally, the total body BMD Z-score by DXA was lower in the CF group,
      although it did not meet the definition of reduced bone density (P = 0.004).
      Biomarkers of inflammation were not different. CONCLUSIONS: In this group of pre
      pubertal children with CF, measures of bone strength and density by both pQCT and
      DXA were reduced compared to healthy controls.

PMID- 29324910
TI  - Deep brain nucleus targeting in Parkinson's disease and essential tremor by image
      guided surgery using neuronavigation system with tractography and volume of
      tissue of activated assessment.
AB  - OBJECTIVE: Deep Brain Stimulation (DBS) is an effective surgical approach for
      treatment of Parkinson's disease (PD), dystonia and essential tremor (ET).
      Traditionally, DBS is performed using frame-based stereotactic technique.
      Recently, image guided surgery (IGS) using neuronavigation has gained popularity
      in neurosurgical procedures. We aim to investigate whether DBS using
      neuronavigation is capable of improving patient's outcome and minimize its
      complications. SUBJECT AND METHODS: From February 2011 to October 2016, 20
      patients with PD and 6 patients with ET were enrolled in the study. Patients aged
      between 18 to 70 years, were included and they underwent Magnetic Resonance
      Imaging (MRI) for deep brain nucleus volumetry. Among PD patients, 14 cases
      underwent subthalamic nucleus (STN) implantation, while other 6 cases underwent
      globus pallidus internus (GPi) implantation. Furthermore, ventral intermediate
      nucleus (VIN) implantation was performed for ET patients, all with IGS using
      neuronavigation system. Patients were assessed by unified Parkinson's disease
      rating scale (UPDRS) for PD and tremor scores for ET in their follow ups. Authors
      utilized Butson model for volume of tissue activated (VTA) assessment. In
      addition, detailed tractography was performed to evaluate white matter circuits
      radiating from deep nucleuses. RESULTS: PD patients with GPi volume of more than
      600mm3 and less than 400mm3 were excluded from the study. Mean right and left GPi
      volume was 519+/-94.2mm3 and 480+/-80.3mm3, respectively. Calculated VTA based on
      Butson model revealed that 70% of cases who exhibited improved UPDRS of more than
      50% in the 7th month of follow-up, had their VTA outside their defined GPi and
      STN boundaries with outer layer overlap. In contrast, 60% of cases who showed
      UPDRS improvement of less than 50% in same follow-up month, have their VTA inside
      defined GPi and STN boundaries. Moreover, ET patients experienced mean 55% and
      79% improvement in tremor scores at mean 6.7 and 9.9 follow up month
      respectively. No surgery related complications were observed. Furthermore,
      tractography analysis revealed increased superior frontal gyrus and thalamus
      connection in patients with improved UPDRS. CONCLUSION: IGS using neuronavigation
      allowed more accurate deep nucleus targeting, minimized intra- and post-operative
      complications and improved clinical outcome in DBS candidate patients. Our study
      revealed that increased white matter connections with remote parts of the brain
      would suggest that isolated deep nucleus stimulation could not explain symptom
      recovery and that patients' specific white matter stimulation by tractography
      coupled with IGS should be in priority.

PMID- 29324911
TI  - Psychological consideration in patients with cerebral gliomas candidates for
      intra-operative radiation therapy based on tumor location.
AB  - OBJECTIVE: Intra-operative Radiation Therapy (IORT) is gaining popularity as an
      adjuvant option to surgical resection, in treatment of glioblastoma multiforme
      (GBM) for increasing survival rate, which a highly aggressive cerebral tumor with
      poor prognosis. Tauhe authors plan to investigate the effects of IORT combined
      with surgical resection on the psychological status of these patients based on
      tumor location. SUBJECT AND METHODS: From December 2013 to February 2017, we have
      enrolled 109 patients with high grade cerebral gliomas, documented by Magnetic
      Resonance Spectroscopy (MRS). Patients with previous history of brain surgery or
      radiation, altered mental status and psychological content and patients diagnosed
      with metastases were excluded. Demographic data, tumor volume based on pre
      operative Magnetic Resonance Imaging (MRI) and psychological status were recorded
      based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition
      (DSM-IV) criteria. The remaining 56 patients, were equally randomized into
      conventional (surgical resection-group A), and trial (surgical resection with
      IORT-group B) who underwent IORT using the 50kV INTRABEAM(r) system (Carl Zeiss
      Meditec AG, Germany). Psychological profiles of both groups were re-evaluated in
      the 3rd post-operative month. RESULTS: Group A consisted of 18 males and 10
      females with mean age of 54.4 years, while group B consisted of 16 males and 12
      females with mean age of 57.8 years. Tumor volumetry revealed mean 81.52cc and
      82.8cc for group A and B respectively. (P value 0.14) Patients were classified
      based on glioma location on pre-operative MRI: a) left parietal lobe (6 in group
      A, 5 in group B); b) left temporal lobe (7 in group A, 5 in group B); c) right
      parietal lobe (5 in group A, 6 in group B); d) left fronto-temporal lobe (4 in
      group A, 6 in group B); e) left parieto-temporal lobe (4 in group A, 5 in group
      B); and, f) right frontal lobe (2 in group A, 1 in group B). Group B received
      mean 8.05 Gy radiation for mean 11.2 minutes. Post-operative psychological in the
      3rd month evaluation revealed the following in each class: a) Group A: 1 mild
      depression, Group B: 1 mild depression and 2 major depression; b) Group A: no
      disorder, Group B: 1 mild depression; c) no disorders in both groups; d) Group A:
      no disorder, Group B: 1 mild depression, 1 major depression and 1 Obsessive
      Compulsive Disorder (OCD); Conclusion: Utilization of IORT is shown to improve
      survival rate of patients suffering from GBM. However, the psychological status
      is a major determinating factor for the quality of life of these patients. Our
      study showed that IORT increased psychological disorders in patients with gliomas
      located in left parietal, left fronto-temporal and left parieto-temporal lobes
      and should be considered in pre-operative strategy selection.

PMID- 29324912
TI  - Diuresis renography and ultrasonography in children with antenatally detected
      hydronephrosis can support diagnoses and suggest related surgery treatment.
AB  - OBJECTIVE: Prenatal ultrasound (US) screening detects the hydronephrosis (HN)
      dilatation of fetal renal collecting system in 1%-5% of all pregnancies. In most
      children, HN is detected by prenatal US screening between 18-20 gestational week.
      Pelvi- ureteric junction (PUJ) stenosis is the most common etiological factor of
      prenatal HN and requires postnatal follow-up. Diuresis renography plays important
      role in the follow-up by complementing morphological information obtained by US
      with the data about differential renal function (DRF) and drainage. We studied
      the association between ultrasound parameters and results of diuresis renography
      in first diagnosed PUJ stenosis and the predictive factors of pyeloplasty in
      order to evaluate the usefulness of diuresis renography in these children
      postnatally. PATIENTS AND METHODS: Children with antenatally detected HN
      attributed to presumed PUJ stenosis were investigated with mercapto
      acetyltriglycine (MAG3) diuresis renography. Parents gave informed consent for
      the procedure. The inclusion criteria were: age up to 4 years, diagnosis of
      prenatal HN determined by US during pregnancy based on the antero-posterior
      diameter (APD) of renal pyelon and at least one post-natal US which confirmed
      diagnosis. Exclusion criteria were: APD of pyelon <10mm, previous surgical
      treatment of HN, vesicoureteral reflux excluded by micturating
      cystourethrography, and patients having any anomaly of the contralateral kidney.
      Sixty two patients 43 boys, 19 girls, median age 16 months were selected. They
      were divided into three groups based on the size of pyelon, three groups based on
      the calyceal size and two groups according to thickness of parenchyma. Renography
      was performed for 24 minutes after the iv. application of 99mTc MAG3, 144 ten-sec
      images were applied. Furosemide was administered after 2 min. (F+2). Post-void
      static images were acquired at 60min. The non-commercial software developed by
      International Atomic Energy Agency was applied to process the studies. The
      criteria for pathological findings (poor or no drainage) were the renographic
      curve maintaining a plateau, Normalized Residual Activity (NORA) at 20.
      min.>1.62, Output efficiency (OE) at 20. min.<71%, postmicturating NORA >0.11.
      The DRF was considered normal within the range of 45%-55%. RESULTS: Good drainage
      had 74% of children, partial drainage 11%, and poor 15%. There was a clear
      association between the size of pyelon, calyces, parenchyma thickness and
      drainage. There was also a clear association between the calyceal size,
      parenchyma thickness and DRF. Differential renal function was <45% in 18% of
      children. A relation between the type of drainage and DRF was not determined.
      Thus, 66.7% of those with poor drainage had preserved DRF. Seven out of nine
      children with poor drainage underwent pyeloplasty. The threshold for pyeloplasty
      was the pyelon of 18mm and calyces of 10mm. The model of the multivariate
      logistic regression which included ultrasound parameters (APD of pyelon, calyces
      size and parenchymal thickness), drainage and DRF, which were significant
      predictors in univariate analysis, showed that only drainage was an independent
      predictor for the need of pyeloplasty. CONCLUSION: Antero-posterior diameter of
      the pyelon <15mm indicates a favorable course of congenital HN in most children.
      Pattern of drainage obtained by diuresis renography was the only independent
      predictor for the need of pyeloplasty.

PMID- 29324913
TI  - The detection of endocarditis, post implantation grafts, arteritis and other
      related disorders by 18F-FDG PET/CT.
AB  - INTRODUCTION: Positron emission tomography with computed tomography (18F-FDG
      PET/CT) is a nuclear medicine diagnostic method which, unlike other technological
      modalities that asses anatomical features, detects increased glucose metabolism
      inside the cells, thus is very helpful in diagnosing cardiovascular infection and
      inflammation and also in therapy planning. AIM: Aim of this study was to assess
      the significance of 18F-FDG PET/CT in detection of an active disease in patients
      with infection and inflammation of cardiovascular system. MATERIAL AND METHODS:
      In this cohort retrospective study 73 cardiovascular patients (56.9+/-15.3 years;
      33 male and 40 female) with persistent symptoms of inflammatory syndrome were
      referred to 18F-FDG PET/CT in order to evaluate active disease. Biochemical blood
      analyses (erytrocite sedimentation, CRP, leukocytic formula), CT, MRI, ultrasound
      were performed in all the patients. Out of 73 patients, 7 had a second 18F-FDG
      PET/CT examination (62.1+/-12.3 years; 6 men and 1 woman) with a previous
      pathological PET/CT finding after which the therapy was changed. The degree of
      metabolic activity was analyzed visually and quantitatively using the maximal
      standardized uptake value (SUVmax). 18F-FDG PET/CT findings were considered
      positive in case of higher focal glucose accumulation in projection of heart and
      diffuse uptake in blood vessels' wall than accumulation in surrounding tissue and
      liver. RESULTS: Vasculitis was diagnosed in 36 patients (49,3%), endocarditis in
      23 (31,5%) and graft inflammation in 14 (19,2%). The results were compared to the
      gold standard, biopsy of the blood vessel and histopathological verification
      during surgical treatment, or clinical follow up. Forty nine patients with the
      sights of an increased FDG uptake were considered true positive (TP) (SUVmax5.7+/
      2.9). In 21 patients 18F-FDG uptake was physiological and they were considered
      true negative (TN). Two who used corticosteroid therapy which decreases
      inflammation, were false negative (FN), and only 1 false positive (FP) finding in
      the region of recent iatrogenic vein injury. Sensitivity of this method was
      96.08+/-, specificity 95.45+/-, positive predictive value 98.0+/-, negative
      predictive value 91.3+/- and accuracy 95.89+/-. CONCLUSION: Our results indicate
      that 18F-FDG PET/CT could be useful diagnostic method for the detection of sights
      of metabolically active disease in patients with persistent symptoms of infection
      and inflammation of cardiovascular system, as well as in monitoring therapy
      response.

PMID- 29324914
TI  - The association between Alzheimer's disease and cancer: Systematic review - Meta
      analysis.
AB  - The objective of the present study was the quantitative assessment of the
      previously documented inverse relationship between Alzheimer's Disease (AD) and
      cancer (CA) by conducting a meta-analysis and evaluating systematic
      differentiations of the aforementioned relationship based on cancer localization.
      For the purpose of the study all available empirical data of the last decade,
      which met specific criteria, were included in the analysis by querying PubMed,
      Web of Science and Cochrane Library databases. Seven studies were included in the
      analysis, with a total sample of 18,887 (10,859 AD patients, 8,028 non-demented
      controls) participants to calculate cancer risk among AD patients, and 11
      studies, with a total of 5,607,076 (1,853,318 cancer patients, 3,753,758 healthy
      controls) participants, were assessed to evaluate AD risk among cancer patients.
      The analysis revealed that AD patients appear to have a reduced risk of cancer,
      by 40% (RR 0.60, 95% CI 0.45 - 0.79), while cancer history was associated with a
      reduced risk of AD, by 15% (RR 0.85, 95% CI 0.77-0.92). Systematic differences
      were also identified based on site-specific cancer. Indications of heterogeneity
      and publication bias were present in the analysis. Our meta-analysis is only the
      fourth conducted on this subject, with newer evidence suggesting a mitigation of
      the inverse relationship. We emphasize the need for new studies to assess the
      inverse comorbidity hypothesis, especially in AD patients.

PMID- 29324915
TI  - Self-report instruments of cognitive failures as screening tools for Subjective
      Cognitive Impairment in older adults.
AB  - BACKGROUND: The term "Subjective Cognitive Impairment (SCI)" is the most widely
      accepted term for cognitive complaints of otherwise apparently healthy older
      adults. It is presently clear that SCI might be a risk factor for the development
      of Mild Cognitive Impairment and dementia. As regards SCI measurement and
      potential diagnosis, several studies showed that SCI is a condition in which
      people score in the normal range on common tests but believe they experience
      cognitive decline. Hence, to assess the characteristic of the SCI subtle
      cognitive decline, self-report measures were developed to estimate "self
      experience" of minimal decline in cognition seem the most appropriate tools. In
      this vein, the present study aimed at examining the capacity of the Greek version
      of two self-report instruments of the aforementioned type to detect SCI in
      community dwelling older adults. MATERIAL AND METHODS: The study sample consisted
      of 295 participants, who were allocated into four age-groups: young adults,
      middle-aged adults, older adults and older-old adults. The first three groups
      were gender and education-matched. The participants were examined via two
      objective tests of the Delis-Kaplan Executive Function System (D-KEFS) which is a
      neuropsychological battery designed to measure executive functions. In specific,
      they were tested via the D-KEFS Tower Test (TT) which mainly measures "planning"
      function, and the D-KEFS Color-Word Interference Test (C-WIT) which primarily
      measures "inhibition" and "switching" functions. Both tests consist of four
      conditions. The participants were also asked to answer to: (a) the Cognitive
      Failures Questionnaire (CFQ), and (b) the Prospective and Retrospective Memory
      Questionnaire (PRMQ), which were designed to assess subjective estimations of
      everyday slips of actions and cognitive failures, and episodic memory slips in
      everyday life, respectively. As concerns the psychometric qualities of the two
      questionnaires, a single-factor structure of the Greek versions of the CFQ and
      the PRMQ was verified in a previous study via the application of Confirmatory
      Factor Analysis. RESULTS: No age-group effects on CFQ score were found. Receiver
      Operating Characteristic (ROC) curve analyses were subsequently performed, using
      objective tests' scores as test variables and CFQ classification based on the
      75th percentile score, as state variable. ROC curves analyses using "C-WIT
      conditions' 1, 2 time of completion" as test variables and CFQ classification, in
      older adult age-group, as state variable, showed that a CFQ score >=47 is
      indicative of an early stage of objective cognitive impairment in older age.
      Cronbach's alpha values, for the Prospective and Retrospective Memory
      Questionnaire ranged from .89 (young adults) to .93 (older adults). No age-group
      effects on PRMQ score were observed. ROC curves analyses were performed, using
      objective measures' scores as well as CFQ score as test variables and PRMQ
      classification based on the 75th percentile score, as state variable. These
      analyses using "C-WIT conditions' 3, 4 time of completion" as well as CFQ score
      as test variables and PRMQ classification, in older adult age-group, as state
      variable, showed that a PRMQ score >=43 is indicative of an early stage of
      objective cognitive impairment as well as of subjective estimations of general
      cognitive decline in older age. CONCLUSION: Self-report questionnaires of
      "everyday" cognitive and memory failures seem to be associated with specific
      objective tests of cognition in aging. Hence, they are useful tools for detecting
      early cognitive impairment at least in older adults. Their administration
      together with objective cognitive tasks of high difficulty could substantially
      help for SCI screening. Given that there is also evidence that the experience of
      subtle impairment in cognition is related to increased likelihood of biomarker
      abnormalities indicative of AD pathology, the assessment of subjective
      estimations is revealed as a useful primary indicator of early AD effects on
      cognitive functioning.

PMID- 29324916
TI  - A comparison of 18F-FDG PET/CT findings in HIV positive compared to HIV negative
      patients with recurrent cervical cancer.
AB  - OBJECTIVE: HIV-positive women with cervical cancer have higher recurrence and
      death rates with shorter time to recurrence and death compared with HIV-negative
      subjects. The objective of this study was to compare the recurrence patterns in
      HIV-positive women with invasive cervical cancer to their HIV-negative
      counterparts using 18F-FDG PET/CT. SUBJECTS AND METHODS: We evaluated 40 HIV-
      seropositive and 79 HIV-seronegative patients with recurrent cervical carcinoma
      using 18F-FDG PET/CT. The PET/CT datasets were interpreted by two independent
      readers blinded to the HIV status of the patients. Areas of disagreement were
      resolved by consensus. Cervical cancer recurrence was confirmed by biopsy and
      histological examination of tissue, correlation with conventional imaging (CT and
      MRI) and by follow-up 18F-FDG PET/CT. RESULTS: HIV-positive patients were 9 years
      younger than the HIV-negative patients at the time of diagnosis; mean age 39
      years versus 48 years respectively. Initial treatment was comparable in both
      groups. Time to recurrence was shorter in HIV-infected compared with HIV
      uninfected women (11 versus 24 months). The commonest sites of metastatic
      recurrence was in the lymph nodes. HIV-infected patients demonstrated significant
      higher recurrence in lymph nodes and lungs (P<0.05). No significant difference in
      the recurrence rate in liver or bone (P>0.05) between both groups. HIV-infected
      patients showed unusual metastases to brain, spleen and skin. CONCLUSION: By
      using the 18F-FDG PET/CT scan we showed that the time to recurrence is shorter
      among HIV seropositive patients with the commonest site of metastatic recurrence
      being in the lymph nodes. Nodal and liver metastases are significantly higher in
      HIV seropositive patients compared with seronegative patients.

PMID- 29324917
TI  - Sequential 18F-FDG PET/CT imaging parameters for differentiating benign from
      malignant lymph nodes in head and neck carcinoma.
AB  - OBJECTIVE: The aim of this study was to differentiate between benign and
      malignant head and neck lymph nodes by sequential imaging. SUBJECTS AND METHODS:
      The total of 56 retrospectively analysed patients with suspected or
      histopathologically confirmed head and neck malignancy (nasopharyngeal cancers
      mainly; 28 patients), before any treatment, underwent sequential fluorine-18
      fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG
      PET/CT) examinations for staging purposes. Remaining 28 patients with physiologic
      and histopathologically confirmed inflammatory (of non-specified origin) lymph
      nodes were included into this analysis. Patients underwent sequential PET/CT
      scans 60 and 90min post injection (p.i.) of the 18F-FDG. Semi-quantitative
      analysis of metabolic activity within lymph nodes was based on the standardized
      uptake value (SUV) evaluation. To compare the metabolic activity fluctuation over
      time, the retention index (RI) was used. For SUV value and RI cut-off evaluation,
      the receiver operating characteristic (ROC) analysis was performed. RESULTS: The
      SUVmax value at 60min p.i. of physiologic, inflammatory and malignant
      (metastatic) lymph nodes were 1.09+/-0.33, 2.36+/-0.60 and 6.31+/-2.74,
      respectively. The SUVmax value at 90min p.i. were: 1.01+/-0.32, 2.48+/-0.61, and
      7.17+/-2.91, respectively, and there was statistically significant difference
      between physiologic and inflammatory and physiologic and the metastatic lymph
      nodes (P<0.001). The values of early and delayed SUVmax were significantly
      different between physiologic and inflammatory and physiologic and metastatic
      lymph nodes (P<0.001). The SUVmax, SUVmean values at 60 and at 90min p.i. between
      malignant and inflammatory lymph nodes were statistically insignificant (P=0.33).
      The RI at 60 and at 90min p.i. was: -6%+/-16% for physiologic, 6%+/-14% for
      inflammatory and 15%+/-13% for the metastatic lymph nodes. The SUVmax changes
      over time (the RI) were statistically significant for physiologic and metastatic
      and physiologic and inflammatory lymph nodes (P<0.001) and significant between
      malignant and inflammatory lymph nodes (P=0.02). CONCLUSION: Sequential delayed
      18F-FDG PET/CT examinations may increase specificity of this scan and provide
      information for the differentiation benign and malignant lymph nodes in the cases
      of head and neck cancer.

PMID- 29324918
TI  - Specific neck pain algometric measurements and their relation to heart rate and
      skin humidity.
AB  - Cervical pain is very common in general population but only few methods have been
      used to evaluate it with objectiveness. There are only few studies which use
      algometer as a means of neck pain assessment. Studies have shown that algometer
      could be used in pain evaluation but more studies are necessary to support this.
      The main purpose of the study was the evaluation of algometer as a means of an
      objective measurement of pain threshold to people with non-specific neck pain.
      The study focused on the search of correlation between neck pain and pain
      pressure threshold (PPT) after recording the number of the minimum pain feeling
      in the sample with the pressure of the algometer at specific neck points. The
      study also aimed at searching the correlation of neck pain with heart rate and
      skin humidity. This is a part of a cross-sectional study which was held during a
      PhD study which assessed 185 randomly chosen people, 20-60 years old, who visited
      all the Public Centers in the County of Thessaloniki. The sample was separated in
      two groups according to the frequency of their neck pain, those who suffered
      frequently or almost every day from non-specific neck pain (neck pain group) and
      those with non-specific neck pain occasionally, rarely or never suffered from it
      (no pain group). Subjects were randomly chosen from people who visited the Public
      Centers for any reason. Neck pain was strongly associated with PPT (P<0.001).
      Heart rate (P=0.216) and skin humidity (P=0.14) were not significantly related to
      neck pain. According to the results the algometer seems to be a useful tool as a
      mean of neck pain evaluation and algometry seems to enhance the idea of pain
      quantification. However more evidence is needed and more studies should be
      conducted in order to strengthen our results. Latter studies should be designed
      with more accuracy focusing on details in order to establish algometry as an
      objective method of pain evaluation.

PMID- 29324919
TI  - Synchrotron-Fourier transform infrared maps of ovalbumin-induced murine chronic
      allergic airways disease: Correlation with conventional histology.
AB  - Asthma is a chronic respiratory disease characterised by airway inflammation,
      remodeling and hyperresponsiveness. The ability to replicate these asthma traits
      in the well-established ovalbumin induced chronic model of allergic airways
      disease is an important tool for asthma research and preclinical drug
      development. Here, spectra derived from focal plane array and Synchrotron-Fourier
      transform infrared maps were used to analyse biochemical changes in lung tissue
      from an ovalbumin-induced murine chronic allergic airways disease model. Analysis
      of the chemical maps resulted in distinct clusters and significant changes in the
      lipid and proteins regions of the spectra between the saline control and diseased
      lung tissue samples. Overall, the utilisation of conventional histological
      methodologies and Synchrotron infrared microspectroscopy has the ability to
      expand the characterisation of murine models of asthma.

PMID- 29324920
TI  - Technetium-99m-dimercaptosuccinic acid renal scintigraphy can guide clinical
      management in congenital hydronephrosis.
AB  - OBJECTIVE: The purpose of this study was to evaluate damage of the kidney with
      technetium-99m-dimercaptosuccinic acid (99mTc-DMSA) scintigraphy in children with
      congenital hydronephrosis (CH) and the influence of other postnatal associated
      diagnoses on abnormal 99mTc-DMSA findings. SUBJECTS AND METHODS: 99mTc-DMSA
      scintigraphy in 54 children (17 girls and 37 boys), aged from 2 months to 5 years
      (median 11 months) with 66 congenital hydronephrotic renal units (RU) (42
      unilateral hydronephrosis-29 boys and 13 girls; 12 bilateral hydronephrosis-8
      boys and 4 girls) was performed. Male/female ratio was 2,2:1,
      unilateral/bilateral hydronephrosis ratio was 4:1. Hydronephrosis classified into
      three groups according to ultrasound measurement of the antero-posterior pelvic
      diameter APD): mild (APD 5-9.9mm) was present in 13/66RU, moderate (APD 10
      14.9mm) in 25/66RU, and severe (APD>=15mm) in 28/66RU. Simple hydronephrosis was
      present in 15RU, and the postnatal associated clinical diagnosis were
      vesicoureteric reflux (VUR) in 21, pelviureteric junction (PUJ) obstruction in 7,
      pyelon et ureter duplex in 11, megaureter in 11 and posterior urethra valves in
      1RU, respectively. Static renal scintigraphy was performed 2 to 3 hours after
      intravenous (iv) injection of 99mTc-DMSA using a dose of 50MUCi/kg (1.85MBq/kg;
      minimal dose: 300MUCi). Four views (posterior, left and right posterior oblique
      and anterior) were obtained with a head gamma camera "Orbiter" filtered with high
      resolution parallel whole collimator. All images were stored in an Pegasys
      computer with a matrix size of 256*256. The relative kidney uptake (RKU) between
      the left and right kidney was calculated as an average number counts from
      anterior and posterior view. Renal pathology was defined as inhomogenous or
      focal/multifocal uptake defects of radiopharmaceutical in hydronephrotic kidney
      or as split renal uptake of <40%, and poor kidney function was defined as split
      renal uptake <10%. Descriptive and analytical statistics (SPSS version 20.0) was
      performed. Analytical statistics implied the non-parametric Mann-Whitney test for
      determination of statistically significant difference between the normal and
      pathological findings on 99mTc-DMS scan. The default level of significance was
      P<.05. RESULTS: Our 99mTc-DMSA scintigraphy findings in children with ANH were:
      decreased or enlarged kidney with inhomogeneous kidney uptake radiopharmaceutical
      in 22, irregular shape kidney with inhomogeneous accumulation of
      radiopharmaceutical in 3, connected (fused) kidney in 1 patient, and poorly or
      nonvisual kidney in 14RU respectively (total 40/66RU with pathological 99mTc-DMSA
      finding, 60,6%). Relative accumulation in hydronephrotic kidney was less or equal
      to 40% in 17RU, less than 10% in 14RU and inhomogeneous radiopharmaceutical
      uptake with relative accumulation over 40% was detected in 9RU. Regular kidney
      morphology with homogeneous accumulation of radiopharmaceutical (normal DMSA
      scintigraphy finding) were found in 26/66RU (39,4%). Statistically significant
      correlation between the degree of the hydronephrosis (APD) and 99mTc-DMSA scan
      findings (P<0.001) and between the degree of the VUR and DMSA scan finding
      (P=0.002) was established. In our study, other associated diagnosis were not
      statistically correlated with pathological findings on 99mTc-DMSA scan due to low
      number of patients. CONCLUSION: On the basis of these results (60% pathological
      findings) we recommend DMSA scintigraphy in the evaluation renal pathology in
      children with congenital hydronephrosis. Greater number of patients is needed for
      the estimation of the associated diagnosis (other than VUR) influence on the
      renal parenchymal damage in children with CH.

PMID- 29324921
TI  - The correlation of Evans index with CSF protein levels and ventriculomegaly.
AB  - OBJECTIVE: The role of ventriculomegaly and its interplay between various
      dementia entities and their pathogenesis, as well as its correlation to the
      levels of CSF protein markers, remains to be elucidated. Evans index (EI) is a
      well-established radiological marker in the diagnosis of idiopathic Normal
      Pressure Hydrocephalus (iNPH), assessing ventricular enlargement. However, there
      are no previous studies investigating the correlation between EI, age, beta
      amyloid (Abeta), tau and phosphorylated-tau (p-tau) proteins in the CSF. The aim
      of this study was to examine the correlation of the above CSF proteins, EI and
      age in patients with dementia. METHODS: Sixty two (62) patients, with dementia
      and levels of Abeta, Tau and p-Tau in their CSF as well as age and the EI
      participated in this study. Multiple regression analysis was performed to
      investigate possible correlations between the aforementioned factors. A multiple
      regression was employed to predict Abeta values from age, tau and p-tau values in
      the CSF. The Durbin-Watson d was 1.942 so we can assume that there is no first
      order linear auto-correlation in our multiple linear regression data. RESULTS:
      The variables statistically significantly predicted Abeta, F-value=4.429,
      P=0.011, R2=0.483. Specifically, out of all the variables, it was shown that only
      EI and age added statistically significantly to the prediction, P<.05.
      Specifically, these results are interpreted as: for every 0.01 unit increase in
      EI, it was predicted a -38.698 decrease in the Alphabeta value and for every 1
      year increase in age, it was predicted a -17 decrease in the Alphabeta value.
      CONCLUSION: There seems to be a significant correlation between EI value, age and
      Abeta reduction in the CSF. No correlation was found between EI and tau and p-tau
      proteins in the CSF. This may indicate that Abeta levels in the CSF are affected
      significantly by ventriculomegaly and not as much by pathophysiological pathways
      characteristic for each dementia entity. On the other hand, tau and p-tau
      proteins could possibly play a crucial role in the differential diagnosis of iNPH
      and other dementia entities, as these proteins cannot be predicted by ventricular
      enlargement.

PMID- 29324922
TI  - Autologous free fat transfer in patients with velopharyngeal insufficiency.
AB  - AIM: To report our initial experience and preliminary results of autologous free
      fat transfer to improve speech and hypernasality in patients with velopharyngeal
      insufficiency (VPI) as a sequela of cleft lip and palate repair. MATERIAL AND
      METHODS: To date 2 patients with a mean age of 25 years were treated with this
      method. Both had initially received multiple procedures elsewhere for cleft lip
      and palate repair. We recorded the number of free fat transfer sessions,
      anatomical places of placement and volumes injected in-patient stay, occurrence
      or absence of complications and effectiveness of this operation in terms of
      clinical speech evaluation, functional velopharyngeal closure measurements and
      speech improvement percentage by an Ear, Nose and Throat (ENT) specialist.
      RESULTS: Two autologous free fat transfer sessions per patient were performed.
      Mean hospitalization time was 1 day per operation. Following liposuction,
      autologous free fat was transferred to the following anatomical areas: a)
      Passavant's ridge, b) uvula, c) palatopharyngeal and palatoglossal folds. The
      volume of fat injected varied from 6.5 cc to 8 cc per session. Postoperative
      periods were uneventful for both cases in each session. On clinical examination,
      improvement in speech was noted as well as a reduction in hypernasality with an
      improvement in articulation and audibility of consonant words, which were also
      reported by the patients' relatives. This was confirmed by objective nasendoscopy
      velopharyngeal closure measurements, both during speech and deglutition.
      CONCLUSION: Augmentation pharyngoveloplasty with autologous free fat transfer in
      patients with velopharyngeal insufficiency is a safe and innovative alternative,
      particularly for small to medium degrees of structural velophayngeal dysfunction.

PMID- 29324923
TI  - The operation of the Day Care Centre of Alzheimer Hellas "Saint Helen" and of the
      Memory Clinic of Papanikolaou General Hospital from 2007 to 2017.
AB  - OBJECTIVE: Nowadays, there is a rapid increase of neurocognitive disorders (ND),
      while Alzheimer disease (AD), is the most frequent type of neurodegeneration.
      Therefore, Day Care Centers (DCC) and Memory Clinics (MC) have been created in
      order to correspond to the rising needs of people with ND. The aim of the study
      was to record clinical and demographic characteristics of people with ND from the
      broader area of Thessaloniki. SUBJECTS AND METHODS: Data bases were collected and
      were analyzed in order to examine demographical characteristics of all visitors
      of the DCC of Alzheimer Hellas and of visitors of the Papanikolaou General
      Hospital, during the years 2007-2017. Six thousand and ninety six people
      (N=6.096) were totally classified as single visitors of the outpatients of MC of
      Papanikolaou General Hospital and of the DCC of Alzheimer Hellas. RESULTS: Among
      the total number of visitors, 3.078 people received the diagnosis of Mild
      Cognitive Impairment (MCI), whereas 3.018 people met the dementia diagnosis
      criteria. As far as the MCI group is concerned, the majority of them were women
      (72.1%) while the mean age of MCI group was M (SD)=67.73(9.21) years. Their mean
      education was M (SD)=10.65 (4.59) years, while their mean score in general
      cognitive performance (MMSE) was M (SD)=27.03(2.18) points and their score of
      general functional performance (FUCAS) was M (SD)=44.32(2.49). In regards to the
      dementia group, the majority of them were also women (63.8%) with a mean age M
      (SD)=76.08 (8.60) years and a mean education M (SD)=7.35 (4.41) years. The MMSE
      score of the group was M (SD)=17.79 (6.53) and the FUCAS score was M (SD)=63.25
      (18.12). Moreover, the vast majority of dementia type was AD (53.1%). CONCLUSION:
      Women are presented more frequently to primary care services and people with
      dementia have lower education and greater age. AD continues to be the most common
      type of dementia.

PMID- 29324924
TI  - Mobile phone use for 5 minutes can cause significant memory impairment in humans.
AB  - INTRODUCTION: Concerns about the possible adverse health effects of mobile phones
      (MP) have increased along with the expansion of their use. A number of research
      papers have tried to address this issue. Although many investigations concluded
      that MP use does have negative consequences, in terms of cognitive function of
      the human brain, the results so far have been divisive. A number of studies
      reported impairment of cognitive function after exposure to mobile phone
      electromagnetic field (MP EMF), while others observed no effect or improved
      performance. The variance in the results may be attributed to methodological
      issues. The present article focuses on possible effects of MP use on cognitive
      function and more specifically on working memory processes. An emphasis is placed
      in the lack of a validated tool, a cognitive task, that can produce MP EMF
      effects on human cognition in a repeatable fashion. METHODS: Sixty four (64)
      healthy participants as well as 20 with Mild Cognitive Impairment (MCI) were the
      experimental group, while 36 healthy individuals were the control group. A
      computerized list of 10 words was presented and the participants were asked to
      reproduce it. The words were presented very briefly in order to increase the
      difficulty and hence the sensitivity of the task. Three measurements were taken
      for the experimental group: a) before using the MP, b) immediately after using
      the MP for a duration of 5 minutes, c) 5 minutes after the second measurement
      with no usage of the MP in between. Three measurements of the memory task were
      also taken for the control group in the same time intervals with no usage of a
      MP. The effect of age and gender in the performance of the task was taken into
      account. RESULTS: Healthy participants of the experimental group performed worst
      in the memory task after using the MP. While the third measurement (5 minutes
      after the 2nd measurement) was better than the second (after using the MP), but
      worse than the first (before using the MP). In contrast for the control group the
      second measurement was better than the first and the third even better than both
      previous ones. All differences were statistically significant. The reduction of
      the performance in the task after using the MP was even higher for the age group
      of 60-80 years old in comparison with younger age groups, as well as for the
      individuals with MCI in comparison to healthy participants. Age was significantly
      negative correlated with performance in the task, while gender showed no
      significant correlation. CONCLUSION: MP use has a significant negative impact on
      working memory performance of human participants. The effect is apparent even for
      a 5 minute use of the MP. Working memory deficits are greater not only for the 60
      years old and above participants but also for individuals with Mild Cognitive
      Impairment. These results are in agreement with previous studies on animals as
      well as humans on the effects of MP use on the brain. It is argued that low
      sensitivity of some of the cognitive tasks used until now and the lack of a
      validated tool in the form of a cognitive task may account for some of the
      variability in the literature so far. It is suggested that the experimental
      paradigm that was used in this study for an increased sensitivity measurement of
      cognitive function and working memory processes in particular may be used for the
      display of the effects of MP use on cognitive function and for the development of
      other tasks sensitive to it. Overall, it is concluded that the development of
      certain restrictions on MP use is necessary for the protection of the brain
      health of the users.

PMID- 29324925
TI  - Bone scintigraphy can diagnose osteoporotic vertebral compression fractures
      better than conventional radiography.
AB  - OBJECTIVE: Most difficult and very frequent complications of osteoporosis are
      vertebral compression fractures (VCF). Bone scintigraphy with 99mTc-phosphonates
      enables early detection of vertebral compression fractures in the first 72 hours
      of occuring. Typical scintigraphic findings is markedly increased radiotracer
      uptake in the linear pattern, throughout collapsed vertebral body. Bone
      scintigraphy is usefull in follow-up of vertebral fractures healing, showing
      reduction of radiotracer uptake in fractured vertebrae. In patients with
      osteoporosis and suspition of VCF, we detected compression vertebral fracture by
      bone scintigraphy and compare it with conventional radiography findings. PATIENTS
      AND METHOD: Bone scintigraphy was done in 40 patients with osteoporosis and
      suspition of compression vertebral fractures, 32 women and 8 men, mean age, 71
      years. Three hours after iv. injection of 740MBq of 99mTc-DPD to the patients, a
      whole body scintigraphy was done. Standard radiographic views AP, lateral, and
      oblique were done in all patients. RESULTS: Radiography findings were positive
      for vertebral compression fracture in 28 patients (70%), and with bone
      scintigraphy in 36 patients (90%). In one patient with healed-old vertebral
      fracture, with positive radiographic finding, scintigraphic finding was negative.
      Bone scintigraphy incidentally diagnosed bone metastases in 3 patients.
      CONCLUSION: Bone scintigraphy has a very high sensitivity for detection of
      vertebral compression fractures in osteoporotic patients. Conventional
      radiography showed a much lower sensitivity and could not differentiate acute
      from old vertebral compression fractures.

PMID- 29324926
TI  - Risk stratification and staging in prostate cancer with prostatic specific
      membrane antigen PET/CTObjective: A one-stop-shop.
AB  - OBJECTIVE: Current imaging modalities for prostate cancer (PC) had limitations
      for risk stratification and staging. Magnetic resonance imaging (MRI) frequently
      underestimated lymphatic metastasis while bone scintigraphy often had diagnostic
      dilemmas. Prostatic specific membrane antigen (PSMA) positron emission tomography
      computed tomography (PET/CT) has been remarkable in diagnosing PC recurrence and
      staging. We hypothesized it can become one-stop-shop for initial risk
      stratification and staging. SUBJECTS AND METHOD: Ninety seven PSMA PET-CT studies
      were re analysed for tumor node metastases (TNM) staging and risk stratification
      of lymphatic and distant metastases proportion. The histopathology of 23/97
      patients was available as gold standard. Chi-square test was used for proportion
      comparison. Sensitivity, specificity, positive predictive value (PPV), negative
      predictive value (NPV), over-estimation, under-estimation and correct-estimation
      of T and N stages were calculated. Cohen's kappa coefficient (k) was derived for
      inter-rater agreement. RESULTS: Lymphic or distant metastases detection on PSMA
      PET/CT increased significantly with increase in risk category. PSMA PET/CT
      sensitivity, specificity, PPV and NPV for extra prostatic extension (EPE),
      seminal vesicle invasion (SVI) and lymphatic metastases were 63.16%, 100%, 100%,
      36.36% & 55%, 100%, 100%, 25% and 65.62%, 99.31%, 87.50%, 97.53%, respectively.
      Cohen's kappa coefficient showed substantial agreement between PSMA PET/CT and
      histopathological lymphic metastases (kappa 0.734) however, it was just in fair
      agreement (kappa 0.277) with T stage. PSMA PET/CT over-estimated, under-estimated
      and correct-estimated T and N stages in 8.71%, 39.13%, 52.17% and 8.71%, 4.35%,
      86.96% cases, respectively. CONCLUSION: We found that PSMA PET/CT has potential
      for initial risk stratifications with reasonable correct estimation for N stage.
      However, it can underestimate T stage. Hence, we suggest that PSMA PET/CT should
      be used for staging and initial risk stratification of PC as one-stop-shop with
      regional MRI in surgically resectable cases.

PMID- 29324927
TI  - Hematopoiesis is prognostic for toxicity and survival of 223Radium treatment in
      patients with metastatic castration-resistant prostate cancer.
AB  - OBJECTIVE: We evaluated the impact of pre-therapeutic hematopoiesis on survival,
      hematotoxicity (HT) and number of 223Radium (223Ra) treatments in patients with
      metastatic castration-resistant prostate cancer. SUBJECTS AND METHOD: Hemoglobin
      levels (Hb), the number of platelets (Plts), leukocytes (Leuk), and survival data
      were collected in 56 patients treated with 223Ra. Pre-therapeutic hematopoiesis
      as well as adverse events during and after therapy were scored (grade 0-4)
      according to the CTCAE recommendations. The association of pre-therapeutic
      hematopoiesis, survival, HT and numbers of 223Ra cycles was analyzed. RESULTS:
      Median survival in all patients was 69.9 weeks; 77% of patients had pre-existing
      impaired Hb (1.7% grade 3, 12.5% grade 2, 62.5% grade 1). 8/56 (14.3%) had
      impaired Plt (grade 1) Maximum toxicity (Tox) grades of patients during treatment
      were grade 4 (Hb 1.7%; Plt 1.7%), grade 3 (Hb 14.3%; Plt 7.1%; Leu 7.1%), grade 2
      (Hb 33.9%; Plt 7.1%; Leu 23.2%), grade 1 (Hb 46.4%; Plt 17.9%; Leu 23.2%) and
      grade 0 (Hb 5.4%; Plt 66.1%; Leu 44.6%). Interestingly, patients with
      thrombocytopenia had a significantly shorter survival compared to those with
      normal Plt levels (21 weeks vs not reached; P<0.003). As expected patients with
      pre-therapeutic low Hb-level (<10g/dL) had a significantly shorter survival
      compared to those with Hb-level >10g/dL (28 weeks vs not reached, P<0.004),
      whereas survival of patients with mildly impaired Hb (>10 but <13.5g/dL) did not
      differ from patients with normal levels of Hb (X vs. Y, P=...). Also patients
      with impaired Hb also developed significantly more grade 3 and 4 HT (Hb <10g/dL:
      42.9 vs 14.3%, P<0.001; Plt <150G/mL: 25.0% vs 6.3%; P=0.002) and received
      significantly fewer treatment cycles (Hb<10g/dL: 5.1 vs 5.8, P<0.04; Plt
      <150G/mL: 3.4 vs 5.6; P<0.001). Neither extent of bone metastases nor previous
      chemotherapy were associated with survival, number of 223Ra cycles and HT.
      CONCLUSION: Patients with metastatic castration-resistant prostate cancer and
      impaired hematopoiesis, in particular thrombocytopenia and anemia, before 223Ra
      therapy suffer from significantly more high-grade HT, shorter survival and
      receive significantly fewer 223Ra treatments. Therefore, Hb-levels and platelet
      counts are essential parameters for adequate patient selection for 223Ra therapy.

PMID- 29324928
TI  - Individual kidney depth determination is mandatory to assess split renal function
      in nephrography irrespective of age.
AB  - Nephrography having been introduced more than 60 years ago still now is one of
      the most frequently used and informative procedures in Nuclear Medicine. Although
      being considered a well standardized method, a worldwide study in 34 centers in
      21 countries revealed that determination of split kidney function shows
      unacceptable high variation, particularly in patients with a relative kidney
      function below 30%. Furthermore, kidney depth usually is not considered. The
      calculation of kidney depth by various formulas available, each claiming to be
      more predictive, is different in races and does not allow individual information,
      which particularly in patients with a diseased kidney may become unreliable. We
      investigated 331 patients (167m, 164f) aged 1 to 76 years (84 of them being less
      than 20 years old), where kidney depth has been estimated by means of sonography
      as well as by a lateral view gamma camera image obtained immediately after the
      investigation. At the age of 10 years the kidney depth may vary already by 20%,
      in some patients increasing to 30% at the age of 20 and showing further increase
      with increasing age. In adults, >50% show a depth difference between right and
      left kidney of >1cm. There is an excellent correlation between sonographic and
      nephrographic kidney depth determination, at mean there was no difference between
      the kidney depth of the right hand and left hand side. Furthermore, we
      demonstrate that the incorporation of waist circumference instead of body mass
      index into the formulas is more precise. These findings indicate that the
      assessment of split kidney function particularly in patients with kidney disease,
      transplant donors and atypical localization irrespective of age should be
      mandatory in clinical routine.

PMID- 29324929
TI  - Our solution for fusion of simultaneusly acquired whole body scintigrams and
      optical images, as usesful tool in clinical practice in patients with
      differentiated thyroid carcinomas after radioiodine therapy. A useful tool in
      clinical practice.
AB  - OBJECTIVE: After radioiodine therapy of differentiated thyroid cancer (DTC)
      patients, whole body scintigraphy (WBS) is standard procedure before releasing
      the patient from the hospital. A common problem is the precise localization of
      regions where the iod-avide tissue is located. Sometimes is practically
      impossible to perform precise topographic localization of such regions. METHOD:
      In order to face this problem, we have developed a low-cost Vision-Fusion system
      for web-camera image acquisition simultaneously with routine scintigraphic whole
      body acquisition including the algorithm for fusion of images given from both
      cameras. For image acquisition in the gamma part of the spectra we used e.cam
      dual head gamma camera (Siemens, Erlangen, Germany) in WBS modality, with matrix
      size of 256*1024 pixels and bed speed of 6cm/min, equipped with high energy
      collimator. For optical image acquisition in visible part of spectra we have used
      web-camera model C905 (Logitech, USA) with Carl Zeiss(r) optics, native
      resolution 1600*1200 pixels, 34o field of view, 30g weight, with autofocus option
      turned "off" and auto white balance turned "on". Web camera is connected to upper
      head of gamma camera (GC) by a holder of lightweight aluminum rod and a plexiglas
      adapter. Our own Vision-Fusion software for image acquisition and coregistration
      was developed using NI LabVIEW programming environment 2015 (National
      Instruments, Texas, USA) and two additional LabVIEW modules: NI Vision
      Acquisition Software (VAS) and NI Vision Development Module (VDM). Vision
      acquisition software enables communication and control between laptop computer
      and web-camera. Vision development module is image processing library used for
      image preprocessing and fusion. Software starts the web-camera image acquisition
      before starting image acquisition on GC and stops it when GC completes the
      acquisition. Web-camera is in continuous acquisition mode with frame rate f
      depending on speed of patient bed movement v (f=v/?cm, where ?cm is a
      displacement step that can be changed in Settings option of Vision-Fusion
      software; by default, ?cm is set to 1cm corresponding to ?p=15 pixels). All
      images captured while patient's bed is moving are processed. Movement of
      patient's bed is checked using cross-correlation of two successive images. After
      each image capturing, algorithm extracts the central region of interest (ROI) of
      the image, with the same width as captured image (1600 pixels) and the height
      that is equal to the ?p displacement in pixels. All extracted central ROI are
      placed next to each other in the overall whole-body image. Stacking of narrow
      central ROI introduces negligible distortion in the overall whole-body image. The
      first step for fusion of the scintigram and the optical image was determination
      of spatial transformation between them. We have made an experiment with two
      markers (point radioactivity sources of 99mTc pertechnetate 1MBq) visible in both
      images (WBS and optical) to find transformation of coordinates between images.
      The distance between point markers is used for spatial coregistration of the
      gamma and optical images. At the end of coregistration process, gamma image is
      rescaled in spatial domain and added to the optical image (green or red channel,
      amplification changeable from user interface). SUBJECTS: We tested our system for
      10 patients with DTC who received radioiodine therapy (8 women and two men, with
      average age of 50.10+/-12.26 years). Five patients received 5.55Gbq, three
      3.70GBq and two 1.85GBq. Whole-body scintigraphy and optical image acquisition
      were performed 72 hours after application of radioiodine therapy. CONCLUSION:
      Based on our first results during clinical testing of our system, we can conclude
      that our system can improve diagnostic possibility of whole body scintigraphy to
      detect thyroid remnant tissue in patients with DTC after radioiodine therapy.

PMID- 29324930
TI  - Characteristics, socioeconomic status and ethnic variations of primary idiopathic
      macular hole repair in vitreoretinal centers in the United Kingdom.
AB  - OBJECTIVE: The purpose of this multicentre retrospective study was to investigate
      the characteristics and role of ethnicity and socioeconomic status amongst
      patients with idiopathic macular holes (IMH) and the surgical outcome. SUBJECTS
      AND METHOD: Consecutive patients undergoing primary IMH surgery at three
      vitreoretinal units in the UK (King's College Hospital, London, UK, Western Eye
      Hospital, London, UK, Sunderland Eye Infirmary, Sunderland, UK) between January
      2007 and May 2017 were included. The main outcome measure was anatomical closure
      of IMH. RESULTS: Two hundred and thirty three primary IMH surgeries were
      included. All patients underwent pars plana vitrectomy, internal limiting
      membrane peeling, and gas tamponade. 69.10% of patients were European Caucasian,
      6.44% were Asian, and 24.46% were Afro-Caribbean. The mean base macular hole
      diameter (BD) was 475.5mcm. Mean BD was 432.2mcm in European Caucasian patients,
      481.3mcm in Asians (P=0.005), and 505.61mcm in Afro-Caribbeans (P=0.006).
      Regression analysis demonstrated that BD and Afro-Caribbean ethnicity were
      independent significant risk factors for surgical failure. Those who have longer
      duration of symptoms (Afro-Caribbeans) and leave in more deprived places (Afro
      Caribbeans) in England where found to have lower success rate on macular hole
      closure. CONCLUSION: Asian and Afro-Caribbean patients present with larger IMH
      than European Caucasians. In addition to IMH base diameter, black origin and
      lower socioeconomic status are independent risk factors for surgical failure.
      This study presents a large population-based data analysis on ethnic variation in
      macular holes and may assist in the management and predicting the surgical
      outcome.

PMID- 29324931
TI  - Vitrectomy with fibrovascular membrane delamination for proliferative diabetic
      retinopathy with or without preoperative Avastin.
AB  - OBJECTIVE: To describe and compare 1. The changes in intraretinal microstructure
      using serial spectral domain optical coherence tomography (SD-OCT) preceding and
      following pars plana vitrectomy and delamination of fibrovascular membranes and
      2. Intraoperative and postoperative complications in patients with proliferative
      diabetic retinopathy (PDR) who had preoperative Avastin (group A) or not (group
      B). SUBJECTS AND METHOD: This retrospective, interventional case series includes
      113 eyes. Outcome measures included LogMAR distance best-corrected visual acuity
      (BCVA), SD-OCT integrity of photoreceptor inner and outer segments junction
      (IS/OS), and integrity of external limiting membrane (ELM), intraoperative and
      postoperative complications. RESULTS: Pre-operative central macular thickness
      (CMT) was significantly correlated with the final post-operative LogMAR BCVA in
      group A. Both groups were also categorised into three sub-groups based on post
      operative IS/OS integrity (group 0: IS/OS intact; group 1: IS/OS irregular but
      not completely disrupted; group 2: IS/OS completely disrupted). Mean BCVA
      improved significantly and IS/OS integrity and ELM integrity postoperatively,
      were significantly and positively correlated with final BCVA in group A.
      Intraoperative complications such as iatrogenic tears and haemorrhage and
      postoperative such as vitreous haemorrhage and neovascular glaucoma were
      significantly less in group A compared to group B. CONCLUSION: Pre-operative
      Avastin reduces the risk of intraoperative and postoperative complications and
      results in better postoperative anatomic and functional outcomes in fibrovascular
      delamination surgery for patients with PDR.

PMID- 29324932
TI  - The neurophysiological and evolutionary considerations of close combat: A modular
      approach.
AB  - Close Combat may be identified as a physical confrontation involving armed or
      unarmed fighting, lethal and/or non-lethal methods, or even simply escape from
      and/or de-escalation of the confrontation. Our model hypothesizes that distinct
      areas of the brain are utilized for specific levels of violence, based on
      evolutionary criteria, and that these levels of violence bring into effect
      distinct physiological criteria and kinesiology. This model is outlined similar
      to Paul D. MacLean's triune brain theory, but incorporates distinct processes
      inherent to the autonomic nervous system (i.e. a "quadrune brain"), and
      correlates the observed level of violence to a particular response to a specific
      neural complex associated with very specific reactive kinesiology in the body.
      Our hypothesis is that the reverse also holds true: specific movements, scenarios
      and breathing will "activate" corresponding neural centres that in turn correlate
      to a respective level of violence. Moreover, socio-historic records bear out the
      premise that specific behavioural violations of social protocols act as
      "triggers" for assaultive and lethal force involving weapons, and it is very
      likely that these triggers (and the concomitant decision to engage in assault or
      lethal force) are processed through neural centres in what McLean has described
      as his "limbic system." A modular system of close combat is being researched and
      developed in accord with the above, readily adaptable to the level of violence
      professional peacekeepers and law enforcement officers may encounter in the
      course of their duties, but also directly relevant to the self-protection needs
      of civilians and youth. Distinct modular training regimes have been identified
      and developed for situations involving escape from a threat, submission of an
      adversary, and assaultive/lethal force, with the hope of strengthening neural
      bridges between the four neural complexes postulated in our model, and therefore
      via these bridges limiting adverse reactions to the psyche from combat stress.

PMID- 29324933
TI  - Brachytherapy in soft tissue tumours: an interdisciplinary challenge!
AB  - OBJECTIVE: Interdisciplinary work including surgery and additive radiotherapy is
      often needed for the therapy of tumours. Beneath this, brachytherapy is an
      important part of the radiotherapy. It was first used over 100 years ago and is
      in regular use after the development of afterload technology in the early 1970s.
      Today it is often used in different tumour therapies, for example in soft tissue
      sarcoma or breast tumours, in order to decrease the risk of local recurrence.
      Concerning its benefits, higher doses could be used because of the localized
      effect with equivalent local control rate and less toxicity of treatment.
      Moreover, brachytherapy can also shorten the treatment time from 5-7 weeks to
      some days and is better reconcilable due to its localized effects, thus reducing
      side effects, as radiation-induced reactions, teleangiectasia and brosis.
      Precondition for application of brachytherapy is the need of a good soft tissue
      coverage and wound healing. Therefore, good interdisciplinary cooperation between
      plastic surgery and radiotherapy is important. After wide surgical resection
      reconstruction with different kind of flaps are often required, for achieving
      early wound healing and fast start of radiotherapy. PATIENTS AND METHOD: Between
      2011 and 2017 we applied brachytherapy to 13 patients with soft tissue sarcomas
      and other tumours like merkel-cell-carcinoma, schwannoma, and breast cancer. The
      treatment consisted of tumour resection, intraoperative insertion of
      brachytherapy catheters and after that brachytherapy alone or in combination with
      external beam radiotherapy. In half of the patients a reconstruction with
      different flaps was required, including pedicled trapezius flap, musculus
      latissimus dorsi flap and radial forearm flap; in some cases nerve and tendon
      reconstruction for better function and faster wound healing and so faster start
      of postoperative brachytherapy was also needed. The mean age of the patients was
      55 years (+/-19) and we could start brachytherapy after 3-21 days after the
      operation, with a mean start on day 8+/-5 postoperatively. Three patients
      received additional percutaneous radiotherapy. The patients who received only
      brachytherapy got a dose of 2, 5 or 3Gy twice daily, with a mean total dose of
      31+/-3Gy. CONCLUSION: Multidisciplinary work, including surgery as the main
      procedure and radiotherapy additionally, is needed for a successful treatment of
      soft tissue tumours. Depending on the type and the stadium of tumour plastic and
      reconstructive surgery provides soft tissue coverage, faster wound healing and
      the chance for limb salvage; on the other hand, additive brachytherapy
      contributes to a good tumour control. Therefore, a close collaboration between
      the two specialties is of particular importance, in order to improve the
      effectiveness of the therapy and the postoperative quality of life of the
      patient.

PMID- 29324934
TI  - Stem cells therapy: the future in the management of systemic sclerosis? A case
      report.
AB  - OBJECTIVE: Systemic sclerosis (SSc) is a connective tissue disorder of unknown
      etiology, with heterogeneous clinical manifestations and chronic and often
      progressive course. The diffuse cutaneous form of SSc (dcSSc) is characterized by
      thickening of the skin (scleroderma) and distinctive involvement of multiple
      internal organs. Patients with limited cutaneous SSc (lcSSc) generally have long
      standing Raynaud's phenomenon before other manifestations of SSc appear. Over the
      last decade the Interest of adipose-derived cell therapy in regenerative medicine
      has increased continuously. In compare to bone marrow-derived mesenchymal stem
      cells (MSCs) adipose tissue-derived stem cells (ADSCs) are considered to be ideal
      for application in regenerative medicine. Zuk et al., introduced a multipotent,
      undifferentiated, self-renewing progenitor cell population isolated from adipose
      tissue, called processed lipoaspirate (PLA). However, subcutaneous injections of
      autologous adipose tissue-derived stromal vascular fraction (ADSVF), which is
      known to contain mesenchymal stem cells, in hands of Patients with scleroderma
      for enhancing their impaired hand function is still in an experimental stage,
      although there are already promising results of the therapy. Commonly available
      therapeutic options for hands of Patients with systemic sclerosis, vasodilatator
      drugs and physiotherapy, have many restriction and limited effects. MATERIALS AND
      METHOD: A 62 years old woman with scleroderma presented with progressive digital
      necrosis, ulceration, gangrene and impaired wound healing, despite of
      conventional therapy with vasodilatator drugs. Water-jet-Assisted Liposuction
      (Body-jet(r) evo, human med AG, Schwerin, Germany) of subcutaneous abdominal fat
      was carried out under general anesthesia by an experienced surgeon. Autologous
      adipose tissue-derived stromal vascular fraction (ADSVF) was harvested by in a
      single-use Q-graft(r) collector (human med AG, Schwerin, Germany). Cells were
      centrifuged in 400G for 5 minutes and cell pellets were aspirated carefully in a
      20mL syringe filled with 0.9% NaCl. A total of ca. 2.72 million cells have been
      isolated. Meanwhile middle phalangeal amputation of digit 2, 3 and 4 of the left
      hand were performed, without closing the skin of the amputation stumps. The SVF
      cell suspension was injected subcutaneous into the area of metacarpophalangeal
      joints in both hands, as well as into the amputation stump of the left middle
      finger, and under a skin necrosis in the right hand. RESULTS: The therapy was
      good tolerated by the patient, with absence of adverse reactions. No infection
      was observed, despite open amputation. Three weeks after the stem cell therapy,
      no need to further amputation was demonstrated. The patient is still under
      regular clinical observation, in order to determine the long term effects of the
      therapy. CONCLUSION: Application of isolated adipose tissue-derived stem cells
      seems to be a very promising procedure in the treatment of the manifestation of
      systemic sclerosis. However, more clinical and experimental studies are required,
      in order to understand the exact mechanisms of action and standardize the
      therapy.

PMID- 29324935
TI  - Right putamen and age are the most discriminant features to diagnose Parkinson's
      disease by using 123I-FP-CIT brain SPET data by using an artificial neural
      network classifier, a classification tree (ClT).
AB  - OBJECTIVE: The differential diagnosis of Parkinson's disease (PD) and other
      conditions, such as essential tremor and drug-induced parkinsonian syndrome or
      normal aging brain, represents a diagnostic challenge. 123I-FP-CIT brain SPET is
      able to contribute to the differential diagnosis. Semiquantitative analysis of
      radiopharmaceutical uptake in basal ganglia (caudate nuclei and putamina) is very
      useful to support the diagnostic process. An artificial neural network classifier
      using 123I-FP-CIT brain SPET data, a classification tree (CIT), was applied. CIT
      is an automatic classifier composed of a set of logical rules, organized as a
      decision tree to produce an optimised threshold based classification of data to
      provide discriminative cut-off values. We applied a CIT to 123I-FP-CIT brain SPET
      semiquantitave data, to obtain cut-off values of radiopharmaceutical uptake
      ratios in caudate nuclei and putamina with the aim to diagnose PD versus other
      conditions. SUBJECTS AND METHOD: We retrospectively investigated 187 patients
      undergoing 123I-FP-CIT brain SPET (Millenium VG, G.E.M.S.) with semiquantitative
      analysis performed with Basal Ganglia (BasGan) V2 software according to EANM
      guidelines; among them 113 resulted affected by PD (PD group) and 74 (N group) by
      other non parkinsonian conditions, such as Essential Tremor and drug-induced PD.
      PD group included 113 subjects (60M and 53F of age: 60-81yrs) having Hoehn and
      Yahr score (HY): 0.5-1.5; Unified Parkinson Disease Rating Scale (UPDRS) score: 6
      38; N group included 74 subjects (36M and 38 F range of age 60-80 yrs). All
      subjects were clinically followed for at least 6-18 months to confirm the
      diagnosis. To examinate data obtained by using CIT, for each of the 1,000
      experiments carried out, 10% of patients were randomly selected as the CIT
      training set, while the remaining 90% validated the trained CIT, and the
      percentage of the validation data correctly classified in the two groups of
      patients was computed. The expected performance of an "average performance CIT"
      was evaluated. RESULTS: For CIT, the probability of correct classification in
      patients with PD was 84.19+/-11.67% (mean+/-SD) and in N patients 93.48+/-6.95%.
      For CIT, the first decision rule provided a value for the right putamen of 2.32+/
      0.16. This means that patients with right putamen values <2.32 were classified as
      having PD. Patients with putamen values >=2.32 underwent further analysis. They
      were classified as N if the right putamen uptake value was >=3.02 or if the value
      for the right putamen was <3.02 and the age was >=67.5 years. Otherwise the
      patients were classified as having PD. Other similar rules on the values of both
      caudate nuclei and left putamen could be used to refine the classification, but
      in our data analysis of these data did not significantly contribute to the
      differential diagnosis. This could be due to an increased number of more severe
      patients with initial prevalence of left clinical symptoms having a worsening in
      right putamen uptake distribution. CONCLUSION: These results show that CIT was
      able to accurately classify PD and non-PD patients by means of 123I-FP-CIT brain
      SPET data and provided also cut-off values able to differentially diagnose these
      groups of patients. Right putamen uptake values resulted as the most discriminant
      to correctly classify our patients, probably due to a certain number of subjects
      with initial prevalence of left clinical symptoms. Finally, the selective
      evaluation of the group of subjects having putamen values >=2.32 disclosed that
      age was a further important feature to classify patients for certain right
      putamen values.

PMID- 29324936
TI  - The impact of lung perfusion scintigraphy in the emergency management of patients
      with suspected pulmonary embolism.
AB  - OBJECTIVE: Pulmonary Embolism (PE) is an emergency condition that requires
      immediate treatment. As the symptoms and the risk factors are nonspecific, PE
      differential diagnosis is often required. Even if angio-CT is considered the gold
      standard for PE diagnosis, the frequent allergic condition and/or chronic renal
      failure of patients make, in most cases, not possible the use of contrast
      enhancement in emergency with even more increasing use of Lung Perfusion
      Scintigraphy (LPS), as a simple and fast examination with no
      preparation/contraindication. The aim of our study is to highlight the role of
      LPS in the management of patients (pts) with suspected PE admitted to our
      hospital as an emergency in the "on-call" 24 hours (hrs) service. MATERIALS AND
      METHOD: We retrospectively revised 2166 LPS performed for suspected PE from
      January 2012 to December 2016, of which 1730 were urgent. LPS was performed
      according to the EANM guidelines in the 4 standard projections. The relation
      between symptoms, risk factors, dosage of D-dimers, other imaging diagnostic
      tools and LPS results were evaluated by contingency tables and Odds Ratio (OR).
      RESULTS: The origin unit of pts was: emergency (56.7%), pneumology (10.8%),
      neurology (4.8%), internal medicine (6.5%), surgery (5.2%), cardiology (3.3%) and
      other departments (11.2%). 59.3% of the examinations were performed during the on
      call 24 hrs service. Symptoms were chest pain in 39%, dyspnea in 75%, cough in
      22%. In 34% were present two symptoms, while 10% were asymptomatic. D-dimer
      dosage before LPS was increased in 97% (>500 ug/L). 55.5% had only one risk
      factor, 18.7% had two or more risk factors. 75.5% of pts had previously performed
      another diagnostic exam (Chest X-ray in 57%, chest CT in 8.4%, both in 10.1%)
      while 24.5% did not undergo previous diagnostic exam. The Chest X-ray and/or
      chest CT resulted negative in 25.4%, suspected for PE in 24.4%, non-specific with
      pleural effusion in 18.8% and non-specific with inflammatory interstitial
      diseases in 31.4%. LSP resulted positive for PE in 17% and then treated; LPS
      resulted negative in the remnant 83%. LPS results were associated with those of
      CT and Rx (chi2=17.5 P=0.001). LPS resulted positive in 13.8% with negative Chest
      X-ray and/or CT, in 23.4% with suspected PE, in 15.2% with pleural effusion and
      in 14.7% with inflammatory interstitial diseases. Furthermore LPS resulted
      positive in 17.32% without previous diagnostic exam. The increased value of D
      Dimers (>500ng/ml) observed in 97% was not predictive of PE (OR=0.598 P=0.152). A
      similar result was observed for cough (OR=1.146 P=0.395) and chest pain (OR=0.927
      P=0.601). Conversely, dyspnea appeared to be a significant symptom of PE
      (OR=1.596 P=0.003). The presence of risk factors is not predictor of PE detected
      by LPS (OR=1.297 P=0.089). CONCLUSION: LPS has a key role in the early diagnosis
      but even more in the exclusion of PE, optimizing the management of pts who do not
      require admission to intensive care unit with high costs and limited
      availability. LPS confirms to be a simple, quick and inexpensive examination. It
      does not require preparation and has no side effect so it can be performed in all
      types of pts including pregnant women, politraumatized and complicated patients,
      with great impact on resource optimization for intensive care units. Our multi
      year and large-scale experience related to a metropolitan area suggests that, to
      date, given the great demand and relevance of this examination, Nuclear Medicine
      Units must necessarily be organized in order to provide LPS as emergency in on
      call 24 hrs service.

PMID- 29324937
TI  - It is not a crisis itself, if does not promote changes.

PMID- 29324939
TI  - Validation of virtual learning object to support the teaching of nursing care
      systematization.
AB  - OBJECTIVE: to describe the content validation process of a Virtual Learning
      Object to support the teaching of nursing care systematization to nursing
      professionals. METHOD: methodological study, with quantitative approach,
      developed according to the methodological reference of Pasquali's psychometry and
      conducted from March to July 2016, from two-stage Delphi procedure. RESULTS: in
      the Delphi 1 stage, eight judges evaluated the Virtual Object; in Delphi 2 stage,
      seven judges evaluated it. The seven screens of the Virtual Object were analyzed
      as to the suitability of its contents. The Virtual Learning Object to support the
      teaching of nursing care systematization was considered valid in its content,
      with a Total Content Validity Coefficient of 0.96. CONCLUSION: it is expected
      that the Virtual Object can support the teaching of nursing care systematization
      in light of appropriate and effective pedagogical approaches.

PMID- 29324938
TI  - Deontological aspects of the nursing profession: understanding the code of
      ethics.
AB  - OBJECTIVE: to investigate nursing professionals' understanding concerning the
      Code of Ethics; to assess the relevance of the Code of Ethics of the nursing
      profession and its use in practice; to identify how problem-solving is performed
      when facing ethical dilemmas in professional practice. METHOD: exploratory
      descriptive study, conducted with 34 (thirty-four) nursing professionals from a
      teaching hospital in Joao Pessoa, PB - Brazil. RESULTS: four thematic categories
      emerged: conception of professional ethics in nursing practice; interpretations
      of ethics in the practice of care; use of the Code of Ethics in the professional
      practice; strategies for solving ethical issues in the professional practice.
      FINAL CONSIDERATIONS: some of the nursing professionals comprehend the meaning
      coherently; others have a limited comprehension, based on jargon. Therefore, a
      deeper understanding of the text contained in this code is necessary so that it
      can be applied into practice, aiming to provide a quality care that is, above
      all, ethical and legal.

PMID- 29324940
TI  - Risk for acute kidney injury in primary health care.
AB  - OBJECTIVE: To identify hypertensive and diabetic patients at risk for developing
      acute kidney injury in the primary health care setting. METHOD: Observational,
      longitudinal, prospective study. Sample of 56 diabetic and hypertensive
      individuals. A semi-structured questionnaire was adopted for data collection. For
      the description of results, were calculated dispersion measures and the Spearman
      test was used for statistical analysis. The result was considered significant
      when p <0.05. RESULTS: Of the total sample, 23.2% of users evolved with renal
      impairment, of which 19.6% with risk for renal injury, and 3.6% with kidney
      injury itself. Age and body mass index were associated with worsening of renal
      function (p = 0.0001; p = 0.0003), respectively. CONCLUSION: A quarter of the
      health system users, hypertensive and diabetic, evolved with impaired renal
      function, more specifically to stages of risk for renal injury and kidney injury
      according to the RIFLE classification.

PMID- 29324941
TI  - Adolescent health promotion based on community-centered arts education.
AB  - OBJECTIVE: To evaluate the contribution of arts education to health promotion of
      adolescents in situations of urban social vulnerability. METHOD: Participatory
      evaluative research, with a qualitative approach, using as a reference the
      theoretical constructs of Paulo Freire's Conscientization and the Empowerment
      Evaluation as a method of collecting with adolescents and teachers of an arts
      education program in the field of the Family Health Strategy. RESULTS:
      Participants constructed a collective mission that represented the concept of
      adolescent health promotion. Arts education activities were prioritized and
      ranked with a mission focus, and over a three-month period, the program
      implemented health goals through art. In the reevaluation, the group presented a
      broad look at the implementation of activities and self-determination for change.
      FINAL CONSIDERATIONS: Arts education is a potential space for nurses to act in
      the conscientization and empowerment of adolescent health in Primary Health Care.

PMID- 29324942
TI  - Mothers' perspective on violence against children: constructing meanings.
AB  - OBJECTIVE: To explore the construct elaborated by the mother on the meaning of
      violence against the child and to identify, according to the mother's
      perspective, which measures are most used for the prevention of this phenomenon.
      METHOD: This is a qualitative research, with the participation of thirty mothers,
      in a health service in the city of Ananindeua, in the state of Para, Brazil. The
      methodology consisted of the categorical content analysis, which identified three
      categories: Violence, Threats of violence and Protective measures. RESULTS: The
      research showed that mothers attribute different meanings to violence, but the
      physical and sexual violence were markedly the most highlighted, and the dialogue
      was the most used protective measure. CONCLUSION: It is essential to strengthen
      public policies through effective interventions, seeking solutions to address
      this phenomenon in all segments of society.

PMID- 29324943
TI  - Knowledge, beliefs, and attitudes of older women in HIV/AIDS prevention.
AB  - OBJECTIVE: To analyze the knowledge, religious beliefs and the adoption of
      preventive measures against HIV/AIDS of non-Catholic elderly women. METHOD: A
      qualitative study, carried out in religious institutions of a municipality in the
      state of Ceara, Northeast Brazil, with 78 elderly women. Of these, 64 were
      evangelicals, seven spiritualists and seven Jehovah's Witnesses. A semi
      structured interview script was used followed by thematic content analysis of
      participants' responses. RESULTS: After analyzing the empirical data, three
      categories were elaborated: the first presented the knowledge they had about
      AIDS; the second, highlighted the beliefs attributed to people with HIV/AIDS; and
      the third, presented the preventive measures to HIV/AIDS adopted by them. FINAL
      CONSIDERATIONS: There were participants with knowledge gaps and failure to use
      preventive measures against HIV/AIDS. They suggested that religious institutions
      can be venues for lectures on HIV/AIDS prevention.

PMID- 29324944
TI  - Cultural adaptation of Quality Of Care Through The Patient's Eyes -QUOTE-HIV.
AB  - OBJECTIVE: to translate and adapt Quality of Care Through the Patient's Eyes -
      HIV (QUOTE-HIV) for the Brazilian population living with HIV/AIDS. METHOD: a
      methodological study, which followed the stages of translation, synthesis, back
      translation, evaluation by the committee of experts and pre-test for cultural
      adaptation of the instrument. RESULTS: the process of translation and cultural
      adaptation was considered adequate. Evaluation by the expert committee resulted
      in semantic, structural and grammatical adequacy of the evaluated items. 30
      subjects considered the instrument to be easy to understand and suggested minor
      adjustments in some items. CONCLUSION: the Brazilian version of QUOTE-HIV has
      been adapted and validated in relation to its content. However, this is a study
      that precedes the process of evaluating the psychometric properties of the
      instrument, the results of which will be presented in a later publication.

PMID- 29324945
TI  - Health advocacy by nurses in the Family Health Strategy: barriers and
      facilitators.
AB  - OBJECTIVE: Identify the barriers and facilitators of health advocacy to users
      delivered by nurses from the Family Health Strategy. METHOD: Qualitative study
      carried out with nurses from the Family Health Strategy of a city in the south of
      Brazil. Study participants were 15 nurses, who were interviewed. The content of
      the interviews was recorded, transcribed and analyzed in the light of the
      discursive text analysis. RESULTS: Two categories emerged, one about the lack of
      organization at the workplace, bureaucracy and limitations to professional work
      in health environments, and another about the facilitating aspects to exercise
      advocacy both individually and collectively. CONCLUSION: When nurses, provided
      with technical, scientific and relational knowledge, are empowered to make
      decisions, they are not only supported by other professionals at work but also
      develop actions of health advocacy to users, thus qualifying the care delivered.

PMID- 29324946
TI  - Realities and perspectives of adolescent mothers in their first pregnancy.
AB  - OBJECTIVE: to understand the trajectory of adolescents regarding the first
      pregnancy, contemplating realities and perspectives. METHOD: qualitative study,
      based on the Schutz theoretical framework, with 30 adolescents assisted in an
      outpatient clinic for adolescents in Fortaleza, Ceara, Brazil. From the narrative
      interviews carried out in the first semester of 2013, in the return for the first
      consultation of the puerperium, the communicative processes were identified, the
      central ideas and units of meanings expressed in the themes were abstracted: I
      was dating and became pregnant; realities and perspectives. RESULTS: adolescents
      justified pregnancy through sexual drive and insufficient prevention; they
      narrated the fear faced, difficulties in motherhood and continuity of studies.
      The realities coexisted with the prospects of family members and partners helping
      to educate the child to achieve a different future from what they themselves
      experienced. FINAL CONSIDERATIONS: adolescents experienced motherhood with
      ambivalent conflicts because they were young mothers, but they wanted to raise
      and educate their children, even those with minimal living conditions.

PMID- 29324947
TI  - Cognitive changes in nurses working in intensive care units.
AB  - OBJECTIVE: To measure the levels of stress, anxiety, and depression of nurses
      working in ICUs, relating them to levels of attention before and after 24 hours.
      METHOD: An observational, quantitative, analytical study with 18 nurses
      undergoing an inventory of stress, anxiety, and depression, as well as assessment
      of attention levels and psychomotor functioning. RESULTS: Sixty-one percent
      showed positive for stress. Depression was observed in 33%; and anxiety in 99.9%.
      A strong correlation between stress and depression (rho = 0.564 with p <0.05) and
      anxiety (rho = 1 with p <0.05) was observed. There was a weak correlation between
      stress and task execution time in M2 (rho = 0.055) for TMT A, a fact that did not
      occur in M0 (rho = -0.249). CONCLUSION: The study shows that the workload of the
      nurses working in 24-hour shifts in the ICU is correlated with high levels of
      stress, decreases in the attention process, and psychomotor decline.

PMID- 29324949
TI  - Training of adolescent multipliers from the perspective of health promotion core
      competencies.
AB  - OBJECTIVE: Recognize the domains of health promotion core competencies in the
      training process of adolescents carried out by nursing students. METHOD:
      Qualitative and descriptive study, which used the theoretical methodological
      contribution Developing Competencies and Professional Standards for Health
      Promotion Capacity Building in Europe (CompHP), carried out with 14 nursing
      students. RESULTS: There were four domains: Enable Change; Mediate through
      Partnership; Communication; and Leadership. These domains came from the interest
      and commitment of adolescents in intersectoral partnership, the use of
      communication techniques, and the role of facilitator to catalyze learning and
      empowerment. CONCLUSION: There were some domains of core competency in the
      training of adolescents, suggesting that nursing students act as health
      promoters. Challenges for Nursing are the implementation of a theoretical
      contribution of CompHP in undergraduate and ongoing training to carry out health
      promotion action.

PMID- 29324948
TI  - Validation of nursing diagnoses, interventions and outcomes in a pediatric
      clinic.
AB  - OBJECTIVES: To elaborate operational definitions for the Nomenclature nursing
      diagnoses, interventionsand outcomes of the Pediatric Clinic at a University
      Hospital and carry out a validation of the content and clinical aspects of this
      Nomenclature. METHOD: Methodological research, developed in two stages:
      documentary study, for the validation of content of the operational definitions
      of nursing diagnoses; and secondly applied research, via clinical cases,
      performed with children from 0 to 5 years. RESULTS: The 126 diagnoses were
      submitted to consensus validation and 55.6% were validated. Six clinical case
      studies were carried out, using the phases of the nursing process, based on the
      theory of Basic Human Needs, identifying 24.3% of the validated diagnoses and
      54.5% of the nursing interventions listed in the Nomenclature. CONCLUSION: The
      study showed the effectiveness of using the Nomenclature in the Pediatric Clinic,
      in order to optimize the care andquality of health services.

PMID- 29324950
TI  - Social determinants of health related to adhesion to mammography screening.
AB  - OBJECTIVE: To identify proximal, intermediary and individual social determinants
      related to mammography adherence, according to the Social Determinants of Health
      model proposed by Dahlgren and Whitehead. Method: Correlational cross-sectional
      study, carried out with a sociodemographic and clinical data questionnaire and
      the Champion's Health Belief Model Scale, translated and adapted for use in
      Brazil. Data analyzed by multiple linear regression, from the domains scale, and
      sociodemographic and clinical variables were used as predictors. RESULTS: The age
      group of 60-64 years (55.0%) was highlighted, 22 (55.0%) women had a stable
      partner; and 14 (65.0%) completed higher education. The domain with the greatest
      influence on adhesion to mammography was perceived barriers. CONCLUSION: The
      social determinants of health are directly related to the levels of adherence to
      the exam among women, as well as the perceived benefits, susceptibilities and
      barriers.

PMID- 29324951
TI  - Signs and symptoms in Gaucher Disease: priority nursing diagnoses.
AB  - OBJECTIVE: Identify the signs and symptoms of patients with Gaucher Disease,
      inferring possible priority nursing diagnoses. METHOD: Cross-sectional study,
      developed in a specialized laboratory, between 2013 and 2015. The sample (n = 91)
      comprised the records of patients with genetic diagnosis for Gaucher Disease. The
      study respected research norms. RESULTS: Prevalence of female sex (57.1%), age at
      diagnosis between 0 and 10 years, and origin from the Southeast Region of Brazil
      were prevalent. Hematologic changes, bone pain, hepatomegaly, splenomegaly, and
      fatigue were the most recurrent signs and symptoms. The inferred diagnoses for
      the studied population were: Risk for bleeding; Fatigue; Chronic pain and Acute
      pain; Impaired physical mobility; Imbalanced nutrition: less than body
      requirements; and Risk for Developmental Delay. CONCLUSION: The establishment of
      Priority Nursing Diagnoses based on signs and symptoms makes it possible to
      achieve expected outcomes for each individual in the care context.

PMID- 29324952
TI  - Analysis of incidents notified in a general hospital.
AB  - OBJECTIVE: To evaluate the incidents spontaneously notified in a general hospital
      in Minas Gerais. METHOD: Retrospective, descriptive, quantitative study performed
      at a general hospital in Montes Claros - Minas Gerais State. The sample comprised
      1,316 incidents reported from 2011 to 2014. The data were submitted to
      descriptive statistical analysis using Statistical Package for the Social
      Sciences version 18.0. RESULTS: The prevalence of incidents was 33.8 per 1,000
      hospitalizations, with an increase during the investigation period and higher
      frequency in hospitalization units, emergency room and surgical center. These
      occurred mostly with adult clients and relative to the medication supply chain.
      The main causes were noncompliance with routines/protocols, necessitating changes
      in routines and training. CONCLUSION: There was a considerable prevalence of
      incidents and increase in notifications during the period investigated, which
      requires the attention of managers and hospital staff. Nevertheless, we observed
      development of the patient safety culture.

PMID- 29324953
TI  - Evaluation of the risk of misidentification of women in a public maternity
      hospital.
AB  - OBJECTIVE: To determine the frequency of similar names and hospital records of
      women in a public teaching maternity hospital and the risk of misidentification
      resulting from the similarity in spelling and pronunciation of the names and in
      records. METHOD: Quantitative, documental and case study of 5,975 admissions that
      occurred between 2011 and 2014. The data name, admission and discharge date, date
      of birth, hospital record and bed number were collected from an electronic
      information system. Analysis encompassed descriptive statistics and design of an
      algorithm for comparison of text and sound. RESULTS: Examination of the names
      revealed that 86% of the misidentification cases resulted from identical surnames
      and 96.5% from a sound similarity in the first names. There were patients with
      identical first and last names at least one day a week. CONCLUSION: The risk of
      misidentification of patients is a reality, which stresses the importance of
      checking and pronouncing the complete names correctly.

PMID- 29324954
TI  - Standard Operational Protocols in professional nursing practice: use, weaknesses
      and potentialities.
AB  - OBJECTIVE: to evaluate the use of Standard Operational Protocols (SOPs) in the
      professional practice of the nursing team based on the theoretical framework of
      Donabedian, as well as to identify the weaknesses and potentialities from its
      implementation. METHOD: Evaluative research, with quantitative approach performed
      with nursing professionals working in the Health Units of a city of Sao Paulo,
      composed of two stages: document analysis and subsequent application of a
      questionnaire to nursing professionals. RESULTS: A total of 247 nursing
      professionals participated and reported changes in the way the interventions were
      performed. The main weaknesses were the small number of professionals, inadequate
      physical structure and lack of materials. Among the potentialities were: the
      standardization of materials and concern of the manager and professional related
      to patient safety. CONCLUSION: The reassessment of SOPs is necessary, as well as
      the adoption of a strategy of permanent education of professionals aiming at
      improving the quality of care provided.

PMID- 29324955
TI  - Burnout and depressive symptoms in intensive care nurses: relationship analysis.
AB  - OBJECTIVE: To analyze the existence of a relationship between burnout and
      depressive symptoms among intensive care unit nursing staff. METHOD: A
      quantitative, descriptive, cross-sectional study with 91 intensive care nurses.
      Data collection used a sociodemographic questionnaire, the Maslach Burnout
      Inventory - Human Services Survey, and the Beck Depression Inventory - I. The
      Pearson test verified the correlation between the burnout dimension score and the
      total score from the Beck Depression Inventory. Fisher's exact test was used to
      analyze whether there is an association between the diseases. RESULTS: Burnout
      was presented by 14.29% of the nurses and 10.98% had symptoms of depression. The
      higher the level of emotional exhaustion and depersonalization, and the lower
      professional accomplishment, the greater the depressive symptoms. The association
      was significant between burnout and depressive symptoms. CONCLUSION: Nurses with
      burnout have a greater possibility of triggering depressive symptoms.

PMID- 29324956
TI  - Identity of primary health care nurses: perception of "doing everything".
AB  - OBJECTIVE: To analyze, in the speeches of nurses, the habitus that conforms their
      professional identity in the primary health care area. METHOD: Qualitative study,
      carried out from March to October 2015, with nurses of primary healthcare units
      in the cities of Cajazeiras, in the state of Paraiba, and Maracanau, in the state
      of Ceara. Data were collected by means of semi-structured interviews, and
      analyzed through discourse analysis. RESULTS: Nurses, in their practice and
      perception, perceive that professional identity is linked to the meaning that
      involves the word "everything". This situation constitutes a habitus that directs
      the range of daily actions, often distant from the profession's core of
      knowledge. FINAL CONSIDERATIONS: Trying to be and do everything in primary health
      care involves negative repercussions in the professional identity of nurses.
      Strategic guidance is necessary in order to achieve and embrace elements that
      reflect the essence of this category.

PMID- 29324957
TI  - Trends in the job market of nurses in the view of managers.
AB  - OBJECTIVE: to identify and interpret the main trends of the labor market for
      nurses in Rio Grande do Norte, based on the opinion of managers of training
      institutions and employers. METHOD: Data were collected through interviews with
      key informants, organized using Atlas.ti software resources and examined under
      the thematic content review. RESULTS: the study showed six trends in the labor
      market of nurses: availability of professionals to the market; worsening working
      conditions with precariousness; indication for insertion in employment;
      unemployment for nurses; shortage of nurses; and the existence of a cooperative
      of nursing professionals. FINAL CONSIDERATIONS: the current scenario of growth in
      the number of registered nurses without the expansion of the job supply has
      remained, unemployment tends to increase and work conditions will worsen.

PMID- 29324958
TI  - Enhancing the process of teaching and learning homecare.
AB  - OBJECTIVE: to identify possibilities for improvement in the process of teaching
      and learning homecare in nursing, pharmacy, medicine, nutrition, dentistry and
      occupational therapy courses. METHOD: qualitative research using the Grounded
      Theory approach. Sixty-three semi-structured interviews were conducted with
      students, teachers and graduates of the six mentioned courses at a public
      university in the south of Brazil. Data analysis was performed through open,
      axial and selective coding. RESULTS: the possibilities for improving the process
      of teaching and learning homecare included: scientific production in the area;
      use of different teaching techniques; development of extracurricular activities;
      extension projects; curricular reformulation; and laboratory simulation. FINAL
      CONSIDERATIONS: the strategies cited in this study enable undergraduate courses
      in health to envisage the possibility of enhance the process of teaching and
      learning homecare.

PMID- 29324959
TI  - Surveillance of intradomiciliary contacts of leprosy cases: perspective of the
      client in a hyperendemic municipality.
AB  - OBJECTIVE: To characterize approach methods for intradomiciliary contacts (IdC)
      of leprosy cases resident in Northern Brazil, during 2001-2012. METHOD: A cross
      sectional and descriptive study in the state of Rondonia. Included IdC of leprosy
      cases diagnosed/reported in SINAN-Ministry of Health (MS), 2001-2012. A semi
      structured instrument was applied to the IdCs, with six interventions: complete
      dermatological examination; complete neurological examination; BCG vaccination;
      instructions for return to the health unit; BCG guidance; and guidance to
      mobilize other contacts.Results: From a total of 459 IdCs included, failure to
      perform the dermatological examination was reported by 191 people (41.6%) and the
      neurological examination, by 252 (54.9%); 138 (30.1%) did not have BCG indicated
      and 122 (26.6%) did not receive guidelines; 257 (56.0%) were not advised to
      return for a new evaluation/follow-up and 186 (40.5%) were not asked to mobilize
      other contacts. CONCLUSION: Despite the favorable indicators of IdC examination
      coverage in the state, the evaluation process presents patterns that indicate
      operational quality failures.

PMID- 29324960
TI  - Impact of critical illness news on the family: hermeneutic phenomenological
      study.
AB  - OBJECTIVE: Understand the impact of critical-illness news on the experience of
      family members at an Intensive Care Unit. METHOD: Phenomenological approach
      according to Van Manen's method. Open interviews were held with 21 family
      members. From analysis and interpretation of the data, three essential themes
      were identified: the unexpected; the pronouncement of death; and the impact on
      self-caring within the family. The study complied with the ethical principles
      inherent to research involving humans. RESULTS: The unexpected news and death of
      the sick person influence the well-being and self-care of family members,
      affecting their ability for analysis and decision making. It was observed that
      the family experiences the news with suffering, mainly due to the anticipation
      arising from the events. FINAL CONSIDERATIONS: The humanity of nurses was
      revealed in response to the needs of the family. In view of the requirements for
      information, it was verified that the information transmitted allowed them to
      become aware of themselves, to become empowered in their daily lives and to
      alleviate the emotional burden experienced.

PMID- 29324962
TI  - Care provided by the father to the child with cancer under the influence of
      masculinities: qualitative meta-synthesis.
AB  - OBJECTIVE: To synthesize and interpret findings and conclusions of qualitative
      research addressing the experience of the father in the care of the child with
      cancer. METHOD: Meta-synthesis of 16 qualitative studies from six databases,
      analyzed through taxonomic analysis. RESULTS: Child and adolescent cancer have
      several repercussions on the daily life of the father, especially related to the
      stigma around the disease, the fear of the unknown and the social and family
      role. Faced with the illness and the need to care for the child, the father seeks
      to recover normality in the family and transitions between hegemonic masculine
      behaviors and practices culturally recognized as female. FINAL CONSIDERATIONS:
      The complex experience of the father, influenced by masculinities, was evidenced.
      The limitations regard the restricted understanding of the contextual
      specificities of the experiences, due to the limited characteristics of the
      parents and children described in the studies. The knowledge produced is useful
      to promote involvement of fathers in the care of the child, as well as to
      strengthen and assist him in this task.

PMID- 29324963
TI  - Quality of life in adults with sickle cell disease: an integrative review of the
      literature.
AB  - OBJECTIVE: To identify the available evidence in the literature on health-related
      quality of life in adults with sickle cell disease. METHOD: integrative review of
      MEDLINE, CUMED, LILACS and SciELO databases, from articles developed in this
      area, published between 2005 and 2015, in English, Portuguese or Spanish.
      RESULTS: 22 articles were included, six scales were used to evaluate health
      related quality of life scores: three generic and three specific. No specific
      scale for adults with sickle cell disease has been adapted to Brazilian
      Portuguese so far. Patients affected by frequent painful crises, with low
      adherence to treatment, had a compromised quality of life. CONCLUSION: Selected
      studies have shown that patients with sickle cell disease have worse scores than
      the general population. These indicators should be instrumental to the nurse in
      the proposal of interventions and strategies of assistance and socio-educational,
      with a view to improving the quality of life of this clientele.

PMID- 29324961
TI  - Naturalization, reciprocity and marks of marital violence: male defendants'
      perceptions.
AB  - OBJECTIVE: to analyze male criminals' perception about marital violence. METHOD:
      An exploratory, descriptive, qualitative study undertaken with 23 men who were
      criminally prosecuted for marital violence. A multimethod data collection was
      conducted, with individual interview and focal group techniques combined, between
      May and December 2015. The data collected were initially categorized using the
      NVIVO(r) 11 software program, and then organized using the Collective Subject
      Discourse method. RESULTS: the collective discourses reveal that, in the male's
      perception, conjugal violence is inherent in a marital relationships: it is a
      private, reciprocal problem that leaves body marks. CONCLUSION: gender
      dissymmetry as a social construct is evidenced, signaling the need to create
      spaces for reflection and re-signification of men and women, from a gender
      perspective.

PMID- 29324964
TI  - Family conference in palliative care: concept analysis.
AB  - OBJECTIVE: to analyze the attributes, antecedents and consequents of the family
      conference concept. METHOD: Walker and Avante's method for concept analysis and
      the stages of the integrative review process, with a selection of publications in
      the PubMed, Cinahl and Lilacs databases focusing on the family conference theme
      in the context of palliative care. RESULTS: the most cited antecedents were the
      presence of doubts and the need to define a care plan. Family reunion and working
      instrument were evidenced as attributes. With respect to consequents, to promote
      the effective communication and to establish a plan of consensual action were the
      most remarkable elements. FINAL CONSIDERATIONS: the scarcity of publications on
      the subject was observed, as well as and the limitation of the empirical studies
      to the space of intensive therapy. Thus, by analyzing the attributes, antecedents
      and consequents of the concept it was possible to follow their evolution and to
      show their efficacy and effectiveness as a therapeutic intervention.

PMID- 29324965
TI  - Analysis of Brazilian publications on distance education in nursing: integrative
      review.
AB  - OBJECTIVE: To analyze the publications that focus on distance education in
      nursing in Brazil from 2010 to 2016. METHOD: Integrative review of the literature
      with data collection in June 2016 in the following databases: LILACS, MEDLINE via
      PUBMED, CINAHL and SCOPUS. For the data analysis and interpretation, the thematic
      categorization was chosen. RESULTS: We selected 18 articles for discussion, whose
      textual analysis permitted the construction of three thematic categories: use of
      virtual technologies for distance education in nursing; construction of virtual
      learning environments with the aid of virtual technologies for distance education
      in nursing; and evaluation of the learning process through virtual technologies
      for distance education of nurses. CONCLUSION: Distance Education stands out as an
      effective teaching-learning strategy in this type of education in Brazilian
      nursing, focused mainly on the improvement and complement of traditional
      teaching.

PMID- 29324966
TI  - Advanced Practice Nursing in Pediatric Urology: experience report in the Federal
      District.
AB  - OBJECTIVE: To describe the creation and implementation of the extension program
      Advanced Practice Nursing in Pediatric Urology, developed in the outpatient
      clinic of a teaching hospital in the Federal District. METHOD: This is an
      experience report regarding the implementation of an outpatient service aimed at
      children and adolescents with symptoms of bladder and bowel dysfunction. RESULTS:
      Because it is an extension program linked to the university, it follows a
      different model of care, valuing empowerment, informed and shared decision
      making, which results in a stronger bond between patients, family and the
      Pediatric Urology nursing team. It has also become a privileged space for the
      production and use of scientific knowledge, associated with the principles of
      evidence-based practice. CONCLUSION: This project shows a different performance
      of the nurse-specialist-professor-researcher in Pediatric Urology Nursing, and it
      has become a reference in the Federal District, mainly for undergraduate and
      graduate nursing students.

PMID- 29324967
TI  - Theoretical saturation in qualitative research: an experience report in interview
      with schoolchildren.
AB  - OBJECTIVE: report the experience of applying the theoretical data saturation
      technique in qualitative research with schoolchildren. METHOD: critical reading
      of primary sources and compilation of raw data, followed by thematic grouping
      through colorimetric codification and allocation of themes/types of statements in
      charts to find theoretical saturation for each grouping. RESULTS: colorimetric
      codification occurred according to previously established themes: bodily
      hydration; physical activities and play; handling of sickle-cell disease; feeding
      and clothing. On the eleventh interview, it was possible to reach the theoretical
      saturation of themes, with four additional interviews being performed.
      CONCLUSION: this experience report enabled the description of the five sequential
      steps for identification of theoretical data saturation in qualitative research
      conducted with schoolchildren.

PMID- 29324968
TI  - Long-Term Effects of an Intensive Lifestyle Intervention on Electrocardiographic
      Criteria for Left Ventricular Hypertrophy: The Look AHEAD Trial.
AB  - BACKGROUND: Left ventricular hypertrophy assessed by electrocardiography (ECG
      LVH) is a marker of subclinical cardiac damage and a strong predictor of
      cardiovascular disease (CVD) events. The prevalence of ECG-LVH is increased in
      obesity and type 2 diabetes; however, there are no data on the long-term effects
      of weight loss on ECG-LVH. The purpose of this study was to determine whether an
      intensive lifestyle intervention (ILI) reduces ECG-LVH in overweight and obese
      adults with type 2 diabetes. METHODS: Data from 4,790 Look AHEAD participants
      (mean age: 58.8 +/- 6.8 years, 63.2% White) who were randomized to a 10-year ILI
      (n = 2,406) or diabetes support and education (DSE, n = 2,384) were included. ECG
      LVH defined by Cornell voltage criteria was assessed every 2 years. Longitudinal
      logistic regression analysis with generalized estimation equations and linear
      mixed models were used to compare the prevalence of ECG-LVH and changes in
      absolute Cornell voltage over time between intervention groups, with tests of
      interactions by sex, race/ethnicity, and baseline CVD status. RESULTS: The
      prevalence of ECG-LVH at baseline was 5.2% in the DSE group and 5.0% in the ILI
      group (P = 0.74). Over a median 9.5 years of follow-up, prevalent ECG-LVH
      increased similarly in both groups (odds ratio: 1.02, 95% confidence interval:
      0.83-1.25; group * time interaction, P = 0.49). Increases in Cornell voltage
      during follow-up were also similar between intervention groups (group * time
      interaction, P = 0.57). Intervention effects were generally similar between
      subgroups of interest. CONCLUSIONS: The Look AHEAD long-term lifestyle
      intervention does not significantly lower ECG-LVH in overweight and obese adults
      with type 2 diabetes. CLINICAL TRIALS REGISTRATION: Trial Number NCT00017953
      (ClinicalTrials.gov).

PMID- 29324970
TI  - Watson for Oncology and breast cancer treatment recommendations: agreement with
      an expert multidisciplinary tumor board.
AB  - Background: Breast cancer oncologists are challenged to personalize care with
      rapidly changing scientific evidence, drug approvals, and treatment guidelines.
      Artificial intelligence (AI) clinical decision-support systems (CDSSs) have the
      potential to help address this challenge. We report here the results of examining
      the level of agreement (concordance) between treatment recommendations made by
      the AI CDSS Watson for Oncology (WFO) and a multidisciplinary tumor board for
      breast cancer. Patients and methods: Treatment recommendations were provided for
      638 breast cancers between 2014 and 2016 at the Manipal Comprehensive Cancer
      Center, Bengaluru, India. WFO provided treatment recommendations for the
      identical cases in 2016. A blinded second review was carried out by the center's
      tumor board in 2016 for all cases in which there was not agreement, to account
      for treatments and guidelines not available before 2016. Treatment
      recommendations were considered concordant if the tumor board recommendations
      were designated 'recommended' or 'for consideration' by WFO. Results: Treatment
      concordance between WFO and the multidisciplinary tumor board occurred in 93% of
      breast cancer cases. Subgroup analysis found that patients with stage I or IV
      disease were less likely to be concordant than patients with stage II or III
      disease. Increasing age was found to have a major impact on concordance.
      Concordance declined significantly (P <= 0.02; P < 0.001) in all age groups
      compared with patients <45 years of age, except for the age group 55-64 years.
      Receptor status was not found to affect concordance. Conclusion: Treatment
      recommendations made by WFO and the tumor board were highly concordant for breast
      cancer cases examined. Breast cancer stage and patient age had significant
      influence on concordance, while receptor status alone did not. This study
      demonstrates that the AI clinical decision-support system WFO may be a helpful
      tool for breast cancer treatment decision making, especially at centers where
      expert breast cancer resources are limited.

PMID- 29324971
TI  - Response to Cherrie Letter, 'How to Quantitatively Assess Dermal Exposure to
      Volatile Organic Compounds'.

PMID- 29324969
TI  - Perspective: APOBEC mutagenesis in drug resistance and immune escape in HIV and
      cancer evolution.
AB  - The apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like (APOBEC)
      mutational signature has only recently been detected in a multitude of cancers
      through next-generation sequencing. In contrast, APOBEC has been a focus of
      virology research for over a decade. Many lessons learnt regarding APOBEC within
      virology are likely to be applicable to cancer. In this review, we explore the
      parallels between the role of APOBEC enzymes in HIV and cancer evolution. We
      discuss data supporting the role of APOBEC mutagenesis in creating HIV genome
      heterogeneity, drug resistance, and immune escape variants. We hypothesize
      similar functions of APOBEC will also hold true in cancer.

PMID- 29324973
TI  - Associations Among Plasma Total Homocysteine Levels, Circadian Blood Pressure
      Variation, and Endothelial Function in Hypertension.

PMID- 29324972
TI  - Prognostic and predictive role of neutrophil/lymphocytes ratio in metastatic
      colorectal cancer: a retrospective analysis of the TRIBE study by GONO.
AB  - Background: Neutrophil/lymphocyte ratio (NLR), defined as absolute neutrophils
      count divided by absolute lymphocytes count, has been reported as poor prognostic
      factor in several neoplastic diseases but only a few data are available about
      unresectable metastatic colorectal cancer (mCRC) patients (pts). The aim of our
      study was to evaluate the prognostic and predictive role of NLR in the TRIBE
      trial. Patients and methods: Pts enrolled in TRIBE trial were included. TRIBE is
      a multicentre phase III trial randomizing unresectable and previously untreated
      mCRC pts to receive FOLFOXIRI or FOLFIRI plus bevacizumab. A cut-off value of 3
      was adopted to discriminate pts with low (NLR < 3) versus high (NLR >= 3) NLR, as
      primary analysis. As secondary analysis, NLR was treated as an ordinal variable
      with three levels based on terciles distribution. Results: NLR at baseline was
      available for 413 patients. After multiple imputation at univariate analysis,
      patients with high NLR had significantly shorter progression-free survival (PFS)
      [hazard ratio (HR) 1.27 (95% CI 1.05-1.55), P = 0.017] and overall survival (OS)
      [HR 1.56 (95% CI 1.25-1.95), P < 0.001] than patients with low NLR. In the
      multivariable model, NLR retained a significant association with OS [HR 1.44 (95%
      CI 1.14-1.82), P = 0.014] but not with PFS [HR 1.18 (95% CI 0.95-1.46), P =
      0.375]. No interaction effect between treatment arm and NLR was evident in terms
      of PFS (P for interaction = 0.536) or OS (P for interaction = 0.831). Patients
      with low [HR 0.84 (95% CI 0.64-1.08)] and high [HR 0.73 (95% CI 0.54-0.97)] NLR
      achieved similar PFS benefit from the triplet and consistent results were
      obtained in terms of OS [HR 0.83 (95% CI 0.62-1.12) for low NLR; HR 0.82 (95% CI
      0.59-1.12) for high NLR]. Conclusion: This study confirmed the prognostic role of
      NLR in mCRC pts treated with bevacizumab plus chemotherapy in the first line,
      showing the worse prognosis of pts with high NLR. The advantage of the triplet is
      independent of NLR at baseline.

PMID- 29324974
TI  - The role of endoplasmic reticulum aminopeptidase 2 in modulating immune detection
      of choriocarcinoma.
AB  - Gestational choriocarcinomas are derived from placental trophoblast cells, with
      HLA-C being the only class I polymorphic molecule expressed. However,
      choriocarcinomas have not been profiled for endoplasmic reticulum aminopeptidase
      2 (ERAP2) expression. ERAP2 trims peptides presented by human leukocyte antigens
      (HLA) that have shown to modulate immune response. Over 50% of choriocarcinomas
      we screened lack ERAP2 expression, which suggests that the absence of ERAP2
      expression allows immune evasion of choriocarcinoma cells. We demonstrate that
      the ability of choriocarcinoma cells to activate lymphocytes was lowest with
      cells lacking ERAP2 (JEG-3) or HLA-C (JAr). This observation suggests that
      activation is dependent on expression of both ERAP2 and HLA-C molecules. In
      addition, an ERAP2 variant in which lysine is changed to asparagine (K392N)
      results in increased trimming activity (165-fold) for hydrophobic peptides and
      biologically never been detected. We hypothesize that homozygosity for the N392
      ERAP2 variant is prohibited because it modulates the immune recognition of
      placental trophoblasts. We demonstrate that NK-cell activation and killing were
      significantly dependent on forced expression of the N392 ERAP2 isoform in JEG-3
      cells. Cytotoxicity was confirmed by 7AAD killing assays showing that N392 ERAP2
      isoform expressing JEG-3 cells had the highest percentage of apoptotic cells
      independent of the expression level of CD11a on lymphocytes. This is the first
      report showing that N392 ERAP2 promotes an immune clearance pathway for
      choriocarcinoma cells, and provides an explanation for why embryonic homozygosity
      for the N392 ERAP2 variant is not detected in any population.

PMID- 29324975
TI  - Strong population bottleneck and repeated demographic expansions of Populus
      adenopoda (Salicaceae) in subtropical China.
AB  - Background and Aims: Glacial refugia and inter-/postglacial recolonization routes
      during the Quaternary of tree species in Europe and North America are well
      understood, but far less is known about those of tree species in subtropical
      eastern Asia. Thus, we have examined the phylogeographic history of Populus
      adenopoda (Salicaceae), one of the few poplars that naturally occur in this
      subtropical area. Methods: Genetic variations across the range of the species in
      subtropical China were surveyed using ten nuclear microsatellite loci and four
      chloroplast fragments (matK, trnG-psbK, psbK-psbI and ndhC-trnV). Coalescent
      based analyses were used to test demographic and migration hypotheses. In
      addition, species distribution models (SDMs) were constructed to infer past,
      present and future potential distributions of the species. Key Results: Thirteen
      chloroplast haplotypes were detected, and haplotype-rich populations were found
      in central and southern parts of the species' range. STRUCTURE analyses of
      nuclear microsatellite loci suggest obvious lineage admixture, especially in
      peripheral and northern populations. DIYABC analysis suggests that the species
      might have experienced two independent rounds of demographic expansions and a
      strong bottleneck in the late Quaternary. SDMs indicate that the species' range
      contracted during the Last Glacial Maximum (LGM), and contracted northward but
      expanded eastward during the Last Interglacial (LIG). Conclusions: Chloroplast
      data and SDMs suggest that P. adenopoda might have survived in multiple glacial
      refugia in central and southern parts of its range during the LGM. Populations of
      the Yunnan-Guizhou Plateau in the southern part have high chloroplast DNA
      diversity, but may have contributed little to the postglacial recolonization of
      northern and eastern parts. The three major demographic events inferred by DIYABC
      coincide with the initiation of the LIG, start of the LGM and end of the LGM,
      respectively. The species may have experienced multiple rounds of range
      contraction during glacial periods and range expansion during interglacial
      periods. Our study corroborates the importance of combining multiple lines of
      evidence when reconstructing Quaternary population evolutionary histories.

PMID- 29324977
TI  - Maternal metabolic, immune, and microbial systems in late pregnancy vary with
      malnutrition in mice.
AB  - Malnutrition is a global threat to pregnancy health and impacts offspring
      development. Establishing an optimal pregnancy environment requires the
      coordination of maternal metabolic and immune pathways, which converge at the
      gut. Diet, metabolic, and immune dysfunctions have been associated with gut
      dysbiosis in the nonpregnant individual. In pregnancy, these states are
      associated with poor pregnancy outcomes and offspring development. However, the
      impact of malnutrition on maternal gut microbes, and their relationships with
      maternal metabolic and immune status, has been largely underexplored. To
      determine the impact of undernutrition and overnutrition on maternal metabolic
      status, inflammation, and the microbiome, and whether relationships exist between
      these systems, pregnant mice were fed either a normal, calorically restricted
      (CR), or a high fat (HF) diet. In late pregnancy, maternal inflammatory and
      metabolic biomarkers were measured and the cecal microbiome was characterized.
      Microbial richness was reduced in HF mothers although they did not gain more
      weight than controls. First trimester weight gain was associated with differences
      in the microbiome. Microbial abundance was associated with altered plasma and gut
      inflammatory phenotypes and peripheral leptin levels. Taxa potentially protective
      against elevated maternal leptin, without the requirement of a CR diet, were
      identified. Suboptimal dietary conditions common during pregnancy adversely
      impact maternal metabolic and immune status and the microbiome. HF nutrition
      exerts the greatest pressures on maternal microbial dynamics and inflammation.
      Key gut bacteria may mediate local and peripheral inflammatory events in response
      to maternal nutrient and metabolic status, with implications for maternal and
      offspring health.

PMID- 29324976
TI  - Ginsenoside Rg1 inhibits apoptosis by increasing autophagy via the AMPK/mTOR
      signaling in serum deprivation macrophages.
AB  - Ginsenoside Rg1 (Rg1) has been widely used in a broad range of cardiovascular and
      cerebral-vascular diseases because of its unique therapeutic properties. However,
      the underlying mechanisms of Rg1 in the treatment of atherosclerosis have not
      been fully explored. This study sought to determine the precise molecular
      mechanisms on how Rg1 might be involved in regulating apoptosis in serum
      deprivation-induced Raw264.7 macrophages and primary bone marrow-derived
      macrophages. Results demonstrated that Rg1 treatment effectively suppressed
      apoptosis and the expression of phosphorylation level of mTOR induced by serum
      deprivation in Raw264.7 macrophages; the expressions of autophagic flux-related
      proteins including Atg5, Beclin1, microtubule-associated protein 1 light chain 3
      (LC3), p62/SQSMT1, and the phosphorylation level of AMPK were concomitantly up
      regulated. 3-Methyl-adennine (3-MA), the most widely used autophagy inhibitor,
      strongly up-regulated the expression of cleaved caspase-3, and blocked the anti
      apoptosis function of Rg1 in macrophages. Importantly, autophagic flux was
      activated by Rg1, while Beclin1 knockdown partially abolished the anti-apoptosis
      of Rg1. Moreover, compound C, an AMPK inhibitor, partially decreased the
      expressions of phosphorylation of mTOR, Atg5, Beclin1, LC3, and p62/SQSMT1, which
      were increased by Rg1. AICAR, an AMPK inducer, promoted the protein expressions
      of phosphorylation of mTOR, Atg5, Beclin1, LC3, and p62/SQSMT1. In conclusion,
      Rg1 significantly suppressed apoptosis induced by serum deprivation in
      macrophages. Furthermore, Rg1 could effectively induce the autophagic flux by
      attenuating serum deprivation-induced apoptosis in Raw264.7 macrophages through
      activating the AMPK/mTOR signaling pathway.

PMID- 29324978
TI  - Effect of fish meal supplementation on luteal sensitivity to intrauterine
      infusions of prostaglandin F2alpha in the bovine.
AB  - Progesterone is a steroid hormone secreted from the corpus luteum (CL), which is
      responsible for establishment and maintenance of pregnancy. Early embryonic
      mortality often occurs due to inadequate regulation of uterine prostaglandin (PG)
      F2alpha secretion, leading to a decrease in progesterone and loss of pregnancy.
      The objective of the current study was to determine the effects of fish meal
      supplementation on luteal sensitivity to intrauterine infusions of PGF2alpha.
      Nonlactating beef cows received corn gluten meal or fish meal supplementation for
      60 days. Cows were administered four intrauterine infusions of 0.25 mL saline at
      6-h intervals (n = 6 corn gluten meal; n = 5 fish meal) or two doses of 0.5 mg
      PGF2alpha in 0.25 mL saline at 12-h intervals (n = 11 corn gluten meal; n = 11
      fish meal) commencing on days 10 to 12 of the estrous cycle. At time of each
      infusion, luteal biopsies were collected to determine the effects of
      supplementation on expression of immediate early and steroidogenic genes involved
      in cholesterol transport and progesterone biosynthesis. Transrectal
      ultrasonography was performed to measure diameter of CL, and blood samples were
      collected to determine serum progesterone. Intrauterine infusion of PGF2alpha
      resulted in upregulation or no change in FOS, NR4A1, and 3BHSD and downregulation
      in LDLR, STARD1, and CYP11A1. Although CL diameter decreased, infusion of
      PGF2alpha resulted in functional regression in 91% of cows supplemented with corn
      gluten meal, and only 46% for fish meal supplemented animals. Results demonstrate
      that fish meal supplementation alters luteal sensitivity to PGF2alpha, which may
      affect fertility.

PMID- 29324979
TI  - Under pressure? Epicormic shoots and traumatic growth zones in high-latitude
      Triassic trees from East Antarctica.
AB  - Background and Aims: Investigating the biology of trees that were growing at high
      latitudes during warmer geological periods is key to understanding the
      functioning of both past and future forest ecosystems. The aim of this study is
      to report the first co-occurrence of epicormic shoots and traumatic growth zones
      in fossil trees from the Triassic of Antarctica and to discuss their biological
      and environmental implications. Methods: Permineralized woods bearing scars of
      epicormic shoots were collected from the Triassic Fremouw Formation in Gordon
      Valley, Central Transantarctic Mountains, Antarctica in 2010. Samples from
      different portions of three specimens were prepared using standard thin section
      and hydrofluoric (HF) acid peel techniques, and anatomical details were studied
      in transmitted light. Key Results: The fossil woods represent the outer part of
      trunks, with at least 40 growth rings that are 0.2-4.8 mm in width. Anatomical
      comparisons suggest that they represent a new tree taxon for the Triassic of
      Antarctica. Numerous small epicormic shoots can be seen crossing the wood almost
      horizontally and are locally branched. Each specimen also contains several
      occurrences of traumatic growth zones located in the early wood, in the cells
      produced either at the very start of the growing season or slightly later.
      Conclusions: This is the first report of epicormic shoots and traumatic growth
      zones in the wood of a Triassic tree from Antarctica. Their co-occurrence
      indicates that these trees from Gordon Valley were subjected to environmental
      stresses not seen in Triassic trees previously described from this region. This
      suggests that they had a different biology and/or were growing in a different
      habitat, which offers a new glimpse into the diversity of high-latitude trees in
      the Triassic greenhouse climate.

PMID- 29324980
TI  - Traits determining the digestibility-decomposability relationships in species
      from Mediterranean rangelands.
AB  - Background and Aims: Forage quality for herbivores and litter quality for
      decomposers are two key plant properties affecting ecosystem carbon and nutrient
      cycling. Although there is a positive relationship between palatability and
      decomposition, very few studies have focused on larger vertebrate herbivores
      while considering links between the digestibility of living leaves and stems and
      the decomposability of litter and associated traits. The hypothesis tested is
      that some defences of living organs would reduce their digestibility and, as a
      consequence, their litter decomposability, through 'afterlife' effects.
      Additionally in high-fertility conditions the presence of intense herbivory would
      select for communities dominated by fast-growing plants, which are able to
      compensate for tissue loss by herbivory, producing both highly digestible organs
      and easily decomposable litter. Methods: Relationships between dry matter
      digestibility and decomposability were quantified in 16 dominant species from
      Mediterranean rangelands, which are subject to management regimes that differ in
      grazing intensity and fertilization. The digestibility and decomposability of
      leaves and stems were estimated at peak standing biomass, in plots that were
      either fertilized and intensively grazed or unfertilized and moderately grazed.
      Several traits were measured on living and senesced organs: fibre content, dry
      matter content and nitrogen, phosphorus and tannin concentrations. Key results:
      Digestibility was positively related to decomposability, both properties being
      influenced in the same direction by management regime, organ and growth forms.
      Digestibility of leaves and stems was negatively related to their fibre
      concentrations, and positively related to their nitrogen concentration.
      Decomposability was more strongly related to traits measured on living organs
      than on litter. Digestibility and decomposition were governed by similar
      structural traits, in particular fibre concentration, affecting both herbivores
      and micro-organisms through the afterlife effects. Conclusions: This study
      contributes to a better understanding of the interspecific relationships between
      forage quality and litter decomposition in leaves and stems and demonstrates the
      key role these traits play in the link between plant and soil via herbivory and
      decomposition. Fibre concentration and dry matter content can be considered as
      good predictors of both digestibility and decomposability.

PMID- 29324982
TI  - Cardiovascular protection by Nox4.

PMID- 29324981
TI  - Outcome in colorectal cancer-tumour, stroma and so much more.

PMID- 29324983
TI  - Pulsatile Hemodynamics Are Associated With Exercise Capacity in Patients With
      Exertional Dyspnea and Preserved Left Ventricular Ejection Fraction.
AB  - BACKGROUND: Pulsatile hemodynamics are associated with left ventricular filling
      pressures and diastolic dysfunction. We investigated their relationship with
      maximum workload and peak oxygen uptake (peak VO2) in patients with exertional
      dyspnea and preserved left ventricular ejection fraction (LVEF). METHODS: Radial
      waveforms from tonometry were processed with a transfer function, pulse wave
      analysis and wave separation analysis, yielding central aortic pressures and
      measures of forward (amplitude of forward wave-Pf) and reflected waves
      (augmentation index-AIx, augmentation pressure-AP, amplitude of backward wave-Pb)
      and their ratio (reflection magnitude). Aortic pulse wave velocity (aoPWV) was
      estimated with a validated formula from single-point waveforms. Ergospirometry
      for assessment of exercise capacity was performed on a bicycle ergometer, using a
      ramp protocol. RESULTS: Sixty-six patients were included (43 females; mean age 66
      years; 83% hypertensives; mean body mass index 28.3 kg/m2). Mean peak VO2 was
      17.0 ml/min/kg, mean achieved maximum workload 104.5 watts (80.9% of a reference
      population). Maximum workload and peak VO2 showed significant inverse
      relationships with AIx, AP, Pb, and aoPWV (r = -0.26 to -0.57). In multiple
      adjusted regression models, brachial and aortic pulse pressure, AP, Pf, Pb, and
      aoPWV were significant independent predictors of maximum workload, whereas AP,
      AIx75, Pf, Pb, and aoPWV were independently related to peak VO2. CONCLUSIONS:
      Pulsatile hemodynamics are independently associated with objective measures of
      exercise capacity in patients with normal LVEF.

PMID- 29324984
TI  - Deoxycorticosterone acetate-salt hypertension activates placental growth factor
      in the spleen to couple sympathetic drive and immune system activation.
AB  - Aims: Chronic increase of mineralocorticoids obtained by administration of
      deoxycorticosterone acetate (DOCA) results in salt-dependent hypertension in
      animals. Despite the lack of a generalized sympathoexcitation, DOCA-salt
      hypertension has been also associated to overdrive of peripheral nervous system
      in organs typically targeted by blood pressure (BP), as kidneys and vasculature.
      Aim of this study was to explore whether DOCA-salt recruits immune system by
      overactivating sympathetic nervous system in lymphoid organs and whether this is
      relevant for hypertension. Methods and results: To evaluate the role of the
      neurosplenic sympathetic drive in DOCA-salt hypertension, we challenged
      splenectomized mice or mice with left coeliac ganglionectomy with DOCA-salt,
      observing that they were both unable to increase BP. Then, we evaluated by
      immunofluorescence and ELISA levels of the placental growth factor (PlGF) upon
      DOCA-salt challenge, which significantly increased the growth factor expression,
      but only in the presence of an intact neurosplenic sympathetic drive. When PlGF
      KO mice were subjected to DOCA-salt, they were significantly protected from the
      increased BP observed in WT mice under same experimental conditions. In addition,
      absence of PlGF hampered DOCA-salt mediated T cells co-stimulation and their
      consequent deployment towards kidneys where they infiltrated tissue and provoked
      end-organ damage. Conclusion: Overall, our study demonstrates that DOCA-salt
      requires an intact sympathetic drive to the spleen for priming of immunity and
      consequent BP increase. The coupling of nervous system and immune cells
      activation in the splenic marginal zone is established through a sympathetic
      mediated PlGF release, suggesting that this pathway could be a valid therapeutic
      target for hypertension.

PMID- 29324985
TI  - Urine Tuberculosis Lipoarabinomannan Predicts Mortality in Hospitalized Human
      Immunodeficiency Virus-Infected Children.
AB  - Clinical Trials Registration: NCT02063880.

PMID- 29324986
TI  - The Impact of the 13-Valent Pneumococcal Conjugate Vaccine on Pneumococcal
      Carriage in the Community Acquired Pneumonia Immunization Trial in Adults
      (CAPiTA) Study.
AB  - Background: The impact of pneumococcal conjugate vaccination on the prevalence of
      nasopharyngeal carriage with pneumococci and other bacteria in adults is unknown.
      The direct effects of the 13-valent pneumococcal conjugate vaccine (PCV13) in
      community dwelling older adults was investigated as part of the randomized
      controlled Community Acquired Pneumonia immunization Trial in Adults (CAPiTA).
      Methods: We determined the carriage of Streptococcus pneumoniae, Staphylococcus
      aureus, Haemophilus influenzae, and Moraxella catarrhalis before and 6, 12, and
      24 months after vaccination using polymerase chain reaction (PCR)-based methods
      and conventional cultures of nasopharyngeal and oropharyngeal swab samples in
      1006 PCV13 recipients and 1005 controls. Serotyping of the 13 vaccine-type (VT)
      pneumococci was performed by PCR targeting capsular synthesis genes and Quellung
      reaction of isolates. Results: Before randomization and based on PCR, 339 of 1891
      subjects had nasopharyngeal carriage with any pneumococci (17.9%), and 114 of
      1891 (6.0%) carried VT pneumococci. At 6 months after vaccination, VT
      pneumococcal carriage was significantly lower in PCV13 recipients than in the
      placebo group (relative risk, 0.53; 95% confidence interval, .35-.80; P = .04).
      There was no difference between the groups at 12 and 24 months after vaccination.
      Carriage of non-VT pneumococci, S. aureus, H. influenzae, and M. catarrhalis did
      not change between groups. Conclusions: In community-dwelling adults aged >=65
      years, a single dose of PCV13 seems to elicit a small and temporary reduction in
      VT carriage 6 months after vaccination. Neither replacement by non-VT serotypes
      nor impact on other nasopharyngeal bacteria was observed.

PMID- 29324987
TI  - The Argument Against Testing for INSTI Resistance in Treatment Naive Patients.

PMID- 29324988
TI  - Evidence for verbal memory enhancement with electrical brain stimulation in the
      lateral temporal cortex.
AB  - Direct electrical stimulation of the human brain can elicit sensory and motor
      perceptions as well as recall of memories. Stimulating higher order association
      areas of the lateral temporal cortex in particular was reported to activate
      visual and auditory memory representations of past experiences (Penfield and
      Perot, 1963). We hypothesized that this effect could be used to modulate memory
      processing. Recent attempts at memory enhancement in the human brain have been
      focused on the hippocampus and other mesial temporal lobe structures, with a few
      reports of memory improvement in small studies of individual brain regions. Here,
      we investigated the effect of stimulation in four brain regions known to support
      declarative memory: hippocampus, parahippocampal neocortex, prefrontal cortex and
      temporal cortex. Intracranial electrode recordings with stimulation were used to
      assess verbal memory performance in a group of 22 patients (nine males). We show
      enhanced performance with electrical stimulation in the lateral temporal cortex
      (paired t-test, P = 0.0067), but not in the other brain regions tested. This
      selective enhancement was observed both on the group level, and for two of the
      four individual subjects stimulated in the temporal cortex. This study shows that
      electrical stimulation in specific brain areas can enhance verbal memory
      performance in humans.awx373media15704855796001.

PMID- 29324990
TI  - Weight gain after smoking cessation does not modify its protective effect on
      myocardial infarction and stroke: evidence from a cohort study of men.
AB  - Aims: This study aimed to investigate the association between smoking cessation,
      post-cessation body mass index (BMI) change and risk of myocardial infarction
      (MI) and stroke in men. Methods and results: A prospective cohort study using the
      National Health Insurance Service (NHIS) data set collected from 2002 to 2013 was
      implemented. Based on the first (2002-03) and second (2004-05) NHIS health check
      up periods, 108 242 men aged over 40 years without previous diagnoses of MI or
      stroke were grouped into sustained smokers, quitters with BMI gain, quitters
      without BMI change, quitters with BMI loss, and non-smokers. Body mass index
      change was defined as the difference of more than 1.0 kg/m2 between the two
      health check-up periods. The participants were followed-up from 1 January 2006 to
      31 December 2013. Hazard ratios (HRs) and 95% confidence intervals (HR, 95% CI)
      were computed using Cox proportional hazard models adjusted for sociodemographic,
      health status, and family health history. Compared to the sustained smokers, the
      risk of MI and stroke was significantly reduced in both quitters with BMI gain
      (HR 0.33; 95% CI 0.16-0.70 for MI and HR 0.75; 95% CI 0.57-1.00 for stroke) and
      without BMI change (HR 0.55; 95% CI 0.37-0.83 for MI and HR 0.75; 95% CI 0.62
      0.92 for stroke), but no significant association was found in quitters with BMI
      loss (HR 0.91; 95% CI 0.43-1.91 for MI and HR 0.86; 95% CI 0.57-1.31 for stroke),
      respectively. Non-smokers had lower risk of MI (HR 0.37; 95% CI 0.32-0.43) and
      stroke (HR 0.68; 95% CI 0.64-0.73) compared to the sustained smokers. Conclusion:
      Post-cessation BMI change did not significantly modify the protective association
      of smoking cessation with MI and stroke.

PMID- 29324991
TI  - ORBITA revisited: what it really means and what it does not?

PMID- 29324989
TI  - Synaptic markers of cognitive decline in neurodegenerative diseases: a proteomic
      approach.
AB  - See Attems and Jellinger (doi:10.1093/brain/awx360) for a scientific commentary
      on this article.Cognitive changes occurring throughout the pathogenesis of
      neurodegenerative diseases are directly linked to synaptic loss. We used in-depth
      proteomics to compare 32 post-mortem human brains in the prefrontal cortex of
      prospectively followed patients with Alzheimer's disease, Parkinson's disease
      with dementia, dementia with Lewy bodies and older adults without dementia. In
      total, we identified 10 325 proteins, 851 of which were synaptic proteins. Levels
      of 25 synaptic proteins were significantly altered in the various dementia
      groups. Significant loss of SNAP47, GAP43, SYBU (syntabulin), LRFN2, SV2C, SYT2
      (synaptotagmin 2), GRIA3 and GRIA4 were further validated on a larger cohort
      comprised of 92 brain samples using ELISA or western blot. Cognitive impairment
      before death and rate of cognitive decline significantly correlated with loss of
      SNAP47, SYBU, LRFN2, SV2C and GRIA3 proteins. Besides differentiating Parkinson's
      disease dementia, dementia with Lewy bodies, and Alzheimer's disease from
      controls with high sensitivity and specificity, synaptic proteins also reliably
      discriminated Parkinson's disease dementia from Alzheimer's disease patients. Our
      results suggest that these particular synaptic proteins have an important
      predictive and discriminative molecular fingerprint in neurodegenerative diseases
      and could be a potential target for early disease intervention.

PMID- 29324992
TI  - Increasing and declining native species in urban remnant grasslands respond
      differently to nitrogen addition and disturbance.
AB  - Background and Aims: Atmospheric nitrogen deposition and natural fire regime
      suppression are key drivers of vegetation change in urbanizing grasslands. Some
      species thrive under these conditions, while others face local extinction. In the
      natural grasslands that surround Melbourne, Australia, biotic homogenization has
      occurred with intensifying urbanization. Some native species have become rarer
      (decreaser species) across the landscape, while others have become more
      widespread (increaser species). This study experimentally examined the response
      of increaser and decreaser plant species to nitrogen addition/depletion, and
      examined the presence/absence of annual disturbance to the vegetation. Methods:
      Decreaser and increaser species were planted into 60 field plots established in
      an urban Melbourne grassland and examined over 2 years. Annual removal of above
      ground biomass occurred in half the plots to simulate biomass removal via fire,
      with the remaining plots undisturbed. Soil nitrogen was depleted in one-third of
      plots, one-third received no nitrogen treatment and one-third were fertilized
      with nitrogen. Increaser plant species were predicted to persist in the absence
      of disturbance, and thrive when fertilized. In contrast, high mortality was
      predicted for decreaser species in the absence of disturbance, with fertilization
      providing no advantage. Key Results: Seedling mortality for increaser and
      decreaser species was unrelated to the treatments. The mortality of decreaser
      species was high (69 %), and the mortality of increaser species low (20 %).
      However, seedling growth was related to the treatments. The total biomass of
      decreaser species was highest in annually disturbed plots, with growth suppressed
      in undisturbed plots. In contrast, the total biomass of increaser species was
      unrelated to the disturbance regime, but responded positively to nitrogen
      enrichment. Conclusions: The results provide evidence that by affecting plant
      growth, declines in biomass removal and atmospheric nitrogen deposition could be
      key drivers of biotic homogenization in urban grasslands.

PMID- 29324993
TI  - The Pros and Cons of the PROs.

PMID- 29324994
TI  - Achieving Viral Suppression in 90% of People Living With Human Immunodeficiency
      Virus on Antiretroviral Therapy in Low- and Middle-Income Countries: Progress,
      Challenges, and Opportunities.
AB  - Although significant progress has been made, the latest data from low- and middle
      income countries show substantial gaps in reaching the third "90%" (viral
      suppression) of the UNAIDS 90-90-90 goals, especially among vulnerable and key
      populations. This article discusses critical gaps and promising, evidence-based
      solutions. There is no simple and/or single approach to achieve the last 90%.
      This will require multifaceted, scalable strategies that engage people living
      with human immunodeficiency virus, motivate long-term treatment adherence, and
      are community-entrenched and -supported, cost-effective, and tailored to a wide
      range of global communities.

PMID- 29324995
TI  - PD-1 blockade with nivolumab in endemic Kaposi sarcoma.

PMID- 29324996
TI  - Laboratory-Confirmed Respiratory Infections as Predictors of Hospital Admission
      for Myocardial Infarction and Stroke: Time-Series Analysis of English Data for
      2004-2015.
AB  - Background: Acute respiratory infections are associated with increased risk of
      myocardial infarction (MI) and stroke; however, the role of different organisms
      is poorly characterized. Methods: Time-series analysis of English hospital
      admissions for MI and stroke (age-stratified: 45-64, 65-74, >=75 years),
      laboratory-confirmed viral respiratory infections, and environmental data for
      2004-2015. Weekly counts of admissions were modeled using multivariable Poisson
      regression with weekly counts of respiratory viruses (influenza, parainfluenza,
      rhinovirus, respiratory syncytial virus [RSV], adenovirus, or human
      metapneumovirus [HMPV]) investigated as predictors. We controlled for
      seasonality, long-term trends, and environmental factors. Results: Weekly
      hospital admissions in adults aged >=45 years averaged 1347 (interquartile range
      [IQR], 1217-1541) for MI and 1175 (IQR, 1023-1395) for stroke. Respiratory
      infections ranged from 11 cases per week (IQR, 5-53) for influenza to 55 (IQR, 7
      127) for rhinovirus. In the adjusted models, all viruses except parainfluenza
      were significantly associated with MI and ischemic stroke admissions in those
      aged >=75. Among 65- to 74-year-olds, adenovirus, rhinovirus, and RSV were
      associated with MI but not ischemic stroke admissions. Respiratory infections
      were not associated with MI or ischemic stroke in people aged 45-64 years, nor
      with hemorrhagic stroke in any age group. An estimated 0.4%-5.7% of MI and
      ischemic stroke admissions may be attributable to respiratory infection.
      Conclusions: We identified small but strongly significant associations in the
      timing of respiratory infection (with HMPV, RSV, influenza, rhinovirus, and
      adenovirus) and MI or ischemic stroke hospitalizations in the elderly. Clinical
      Trials Registration: NCT02984280.

PMID- 29324999
TI  - Changing definition of hypertension in guidelines: how innocent a number game?

PMID- 29324998
TI  - Introducing turgor-driven growth dynamics into functional-structural plant
      models.
AB  - Background and Aims: In many scenarios the availability of assimilated carbon is
      not the constraining factor of plant growth. Rather, organ growth appears driven
      by sink activity in which water availability plays a determinant role. Current
      functional-structural plant models (FSPMs) mainly focus on plant-carbon relations
      and largely disregard the importance of plant water status in organogenesis.
      Consequently, incorporating a turgor-driven growth concept, coupling carbon and
      water dynamics in an FSPM, presents a significant improvement towards capturing
      plant development in a more mechanistic manner. Methods: An existing process
      based water flow and storage model served as a basis for implementing water
      control in FSPMs. Its concepts were adjusted to the scale of individual plant
      organs and interwoven with the basic principles of modelling carbon dynamics to
      allow evaluation of turgor pressure across the entire plant. This was then linked
      to plant organ growth by applying the principles of the widely used Lockhart
      equation. Key results: This model successfully integrates a mechanistic
      understanding of plant water transport dynamics coupled with simple carbon
      dynamics within a dynamically developing plant architecture. It allows evaluation
      of turgor pressure on the scale of plant organs, resulting in clear diel and long
      term patterns, directly linked to plant organ growth. Conclusions: A conceptual
      sap flow and turgor-driven growth model was introduced for functional-structural
      plant modelling. It is applicable to any plant architecture and allows visual
      exploration of the diel patterns of organ water content and growth. Integrated in
      existing FSPMs, this new concept fosters an array of possibilities for FSPMs, as
      it presents a different formulation of growth in terms of local processes,
      influenced by local and external conditions.

PMID- 29324997
TI  - Skin lighteners and hair relaxers as risk factors for breast cancer: results from
      the Ghana breast health study.
AB  - Skin lighteners and hair relaxers, both common among women of African descent,
      have been suggested as possibly affecting breast cancer risk. In Accra and
      Kumasi, Ghana, we collected detailed information on usage patterns of both
      exposures among 1131 invasive breast cancer cases and 2106 population controls.
      Multivariate analyses estimated odds ratios (ORs) and 95% confidence intervals
      (CIs) after adjustment for breast cancer risk factors. Control usage was 25.8%
      for ever use of skin lighteners and 90.0% for use of hair relaxers for >1 year.
      The OR for skin lighteners was 1.10 (95% CI 0.93-1.32), with higher risks for
      former (1.21, 0.98-1.50) than current (0.96, 0.74-1.24) users. No significant
      dose-response relations were seen by duration, age at first use or frequency of
      use. In contrast, an OR of 1.58 (95% CI 1.15-2.18) was associated with use of
      hair relaxers, with higher risks for former (2.22, 1.56-3.16) than current (1.39,
      1.00-1.93) users. Although numbers of burns were inconsistently related to risk,
      associations increased with duration of use, restricted to women who
      predominately used non-lye products (P for trend < 0.01). This was most
      pronounced among women with few children and those with smaller tumors,
      suggesting a possible role for other unmeasured lifestyle factors. This study
      does not implicate a substantial role for skin lighteners as breast cancer risk
      factors, but the findings regarding hair relaxers were less reassuring. The
      effects of skin lighteners and hair relaxers on breast cancer should continue to
      be monitored, especially given some biologic plausibility for their affecting
      risk.

PMID- 29325000
TI  - Alcohol, tobacco and health care costs: a population-wide cohort study (n = 606
      947 patients) of current drinkers based on medical and administrative health
      records from Catalonia.
AB  - Background: Most cost of illness studies are based on models where information on
      exposure is combined with risk information from meta-analyses, and the resulting
      attributable fractions are applied to the number of cases. Methods: This study
      presents data on alcohol and tobacco use for 2011 and 2012 obtained from a
      routine medical practice in Catalonia of 606 947 patients, 18 years of age and
      older, as compared with health care costs for 2013 (all costs from the public
      health care system: primary health care visits, hospital admissions, laboratory
      and medical tests, outpatient visits to specialists, emergency department visits
      and pharmacy expenses). Quasi-Poisson regressions were used to assess the
      association between alcohol consumption and smoking status and health care costs
      (adjusted for age and socio-economic status). Results: Resulting health care
      costs per person per year amounted to 1290 Euros in 2013, and were 20.1% higher
      for men than for women. Sex, alcohol consumption, tobacco use and socio-economic
      status were all associated with health care costs. In particular, alcohol
      consumption had a positive dose-response association with health care costs.
      Similarly, both smokers and former smokers had higher health care costs than did
      people who never smoked. Conclusions: Alcohol and tobacco use had modest and
      large impacts respectively on health care costs, confirming the results of
      previous ecological modelling analyses. Reductions of alcohol consumption and
      smoking through public policies and via early identification and brief
      interventions would likely be associated with reductions in health care costs.

PMID- 29325001
TI  - Hydrogen peroxide acts downstream of melatonin to induce lateral root formation.
AB  - Background and Aims: Although several studies have confirmed the beneficial roles
      of exogenous melatonin in lateral root (LR) formation, the molecular mechanism is
      still elusive. Here, the role of hydrogen peroxide (H2O2) in the induction of LR
      formation triggered by melatonin was investigated. Methods: Alfalfa (Medicago
      sativa 'Biaogan') and transgenic Arabidopsis seedlings were treated with or
      without melatonin, diphenyleneiodonium (DPI, NADPH oxidase inhibitor), N,N'
      dimethylthiourea (DMTU, H2O2 scavenger), alone or combined. Then, H2O2 content
      was determined with 2',7'-dichlorofluorescein diacetate (H2DCFDA)-dependent
      fluorescence and spectrophotography. Transcript levels of cell cycle regulatory
      genes were analysed by real-time reverse transcription-PCR. Key Results:
      Application of exogenous melatonin not only increased endogenous H2O2 content but
      also induced LR formation in alfalfa seedlings. Consistently, melatonin-induced
      LR primordia exhibited an accelerated response. These inducible responses were
      significantly blocked when DPI or DMTU was applied. Compared with the wild-type,
      transgenic Arabidopsis plants overexpressing alfalfa MsSNAT (a melatonin
      synthesis gene) increased H2O2 accumulation and thereafter LR formation, both of
      which were blocked by DPI or DMTU. Similarly, melatonin-modulated expression of
      marker genes responsible for LR formation, including MsCDKB1;1, MsCDKB2;1,
      AtCDKB1;1 and AtCDKB2;1, was obviously impaired by the removal of H2O2 in both
      alfalfa and transgenic Arabidopsis plants. Conclusions: Pharmacological and
      genetic evidence revealed that endogenous melatonin-triggered LR formation was
      H2O2-dependent.

PMID- 29325003
TI  - Reversible colour change in leaves enhances pollinator attraction and
      reproductive success in Saururus chinensis (Saururaceae).
AB  - Background and Aims: Although there has been much experimental work on leaf
      colour change associated with selection generated by abiotic environmental
      factors and antagonists, the role of leaf colour change in pollinator attraction
      has been largely ignored. We tested whether whitening of the apical leaves
      subtending the inflorescences of Saururus chinensis during flowering enhances
      pollinator attraction, and whether re-greening of the white leaves after
      flowering increases carbon assimilation and promotes seed development. Methods:
      White leaves were removed or covered, and the effects of these manipulations on
      pollinator visitation and subsequent reproductive success were assessed. The net
      photosynthetic rates of leaves of different colour were measured and their
      photosynthetic contributions to seed development were evaluated. Key Results:
      Saururus chinensis is able to self-pollinate autonomously, but depends largely on
      flies for pollination. White leaves had different reflectance spectra from green
      leaves, and white leaves attracted significantly more pollinators and led to
      significantly higher fruit and seed set. Although leaf whitening resulted in a
      reduction in photosynthetic capacity, it translated into only a small decrease in
      seed mass. When leaves had turned back from white to green after flowering their
      photosynthetic capacity was similar to that of 'normal' green leaves and promoted
      seed development. Conclusions: The reversible leaf colour change in S. chinensis
      appears to be adaptive because it enhances pollination success during flowering,
      with a small photosynthetic cost, while re-greening of these leaves after
      flowering helps to meet the carbon requirements for seed development.

PMID- 29325005
TI  - Corrigendum to: The Population Health Research Institute.

PMID- 29325002
TI  - Traits and trade-offs in whole-tree hydraulic architecture along the vertical
      axis of Eucalyptus grandis.
AB  - Background and Aims: Sapwood traits like vessel diameter and intervessel pit
      characteristics play key roles in maintaining hydraulic integrity of trees.
      Surprisingly little is known about how sapwood traits covary with tree height and
      how such trait-based variation could affect the efficiency of water transport in
      tall trees. This study presents a detailed analysis of structural and functional
      traits along the vertical axes of tall Eucalyptus grandis trees. Methods: To
      assess a wide range of anatomical and physiological traits, light and electron
      microscopy was used, as well as field measurements of tree architecture, water
      use, stem water potential and leaf area distribution. Key Results: Strong apical
      dominance of water transport resulted in increased volumetric water supply per
      unit leaf area with tree height. This was realized by continued narrowing (from
      250 to 20 um) and an exponential increase in frequency (from 600 to 13 000 cm-2)
      of vessels towards the apex. The widest vessels were detected at least 4 m above
      the stem base, where they were associated with the thickest intervessel pit
      membranes. In addition, this study established the lower limit of pit membrane
      thickness in tall E. grandis at ~375 nm. This minimum thickness was maintained
      over a large distance in the upper stem, where vessel diameters continued to
      narrow. Conclusions: The analyses of xylem ultrastructure revealed complex,
      synchronized trait covariation and trade-offs with increasing height in E.
      grandis. Anatomical traits related to xylem vessels and those related to
      architecture of pit membranes were found to increase efficiency and apical
      dominance of water transport. This study underlines the importance of studying
      tree hydraulic functioning at organismal scale. Results presented here will
      improve understanding height-dependent structure-function patterns in tall trees.

PMID- 29325004
TI  - Association between physical exercise and psychosocial problems in 96 617 Dutch
      adolescents in secondary education: a cross-sectional study.
AB  - Background: Psychosocial problems negatively affect school performance, social
      skills and mental development. In recent years, researchers have investigated the
      relationship between physical activity and psychological health. With this large
      school-based study, we examined whether physically inactive adolescents and
      slightly active adolescents experience more psychosocial problems compared with
      active adolescents. Methods: This study is based on the Dutch National Youth
      Health Monitor. This monitor uses a, school-based, cross-sectional questionnaire
      conducted among 96 617 adolescents in 2015. To examine the association between
      physical exercise and psychosocial problems, multi-level linear regression was
      carried out. Results: The weighted average Strengths and Difficulties
      Questionnaire score of active adolescents was lower than that of inactive
      adolescents. Adolescents who are inactive had 12% (beta = 1.12; 95% CI: 1.10
      1.14; P <0 .001) more psychosocial problems compared with active adolescents.
      Further, inactive adolescents had a higher score on the subscales emotional
      problems (beta = 1.19; 95% CI: 1.17-1.22; P < 0.001) and problems with peers
      (beta = 1.16; 95% CI: 1.14-1.19; P < 0.001). There was no statistical significant
      difference in total score of the Strengths and Difficulties Questionnaire between
      active and slightly active adolescents. Conclusion: Physically active adolescents
      have fewer psychosocial problems compared with physically inactive adolescents.
      Not only is this association significant, but there is an indication that it is
      also of clinical relevance.

PMID- 29325006
TI  - Emergency cardiac surgery following TAVI: implications for the future.

PMID- 29325007
TI  - Rifampicin treatment of Blattella germanica evidences a fecal transmission route
      of their gut microbiota.
AB  - Eukaryotes have established symbiotic relationship with microorganisms, which
      enables them to accomplish functions that they cannot perform alone. In the
      German cockroach, Blattella germanica, the obligate endosymbiont Blattabacterium
      coexists with a rich gut microbiota. The transmission of Blattabacterium is
      vertical, but little is known about how the gut microbiota colonizes newborn
      individuals. In this study, we treated B. germanica populations with rifampicin,
      a broad-spectrum antibiotic, during two generations and analyzed gut bacterial
      composition and the Blattabacterium load in control and rifampicin-treated
      populations. Rifampicin exerted a drastic effect on gut microbiota composition,
      which recovered in the second generation in the case where the antibiotic was not
      added to the diet. Furthermore, we observed that bacterial species present in the
      diet, and particularly in the feces, contribute significantly to establishing the
      gut microbiota. Finally, the Blattabacterium population remained unaffected by
      the antibiotic treatment of adults during the first generation but was strongly
      reduced in the second generation, suggesting that this intracellular symbiont is
      sensitive to rifampicin only during the infection of the mature oocytes, when it
      is in an extracellular stage.

PMID- 29325008
TI  - Mineralized trichomes in Boraginales: complex microscale heterogeneity and simple
      phylogenetic patterns.
AB  - Background and Aims: Boraginales are often characterized by a dense cover of
      stiff, mineralized trichomes, which may act as a first line of defence against
      herbivores. Recent studies have demonstrated that the widely reported silica and
      calcium carbonate in plant trichomes may be replaced by calcium phosphate. The
      present study investigates mineralization patterns in 42 species from nine
      families of the order Boraginales to investigate detailed patterns of
      mineralization and the possible presence of a phylogenetic signal in different
      mineralization patterns. Methods: The distribution of biominerals was analysed by
      scanning electron microscopy (SEM) including cryo-SEM and energy-dispersive X-ray
      analyses with element mapping. The observed distribution of biominerals was
      plotted onto a published phylogeny of the Boraginales. Three colours were
      selected to represent the principal elements: Si (red), Ca (green) and P (blue).
      Key Results: Calcium carbonate was present in the mineralized trichomes of all 42
      species investigated, silica in 30 and calcium phosphate in 25; multiple
      mineralization with calcium carbonate and silica or calcium phosphate was found
      in all species, and 13 of the species were mineralized with all three
      biominerals. Trichome tips featured the most regular pattern - nearly all were
      exclusively mineralized with either silica or calcium phosphate.
      Biomineralization of the trichome shafts and bases was found to be more variable
      between species. However, the trichome bases were also frequently mineralized
      with calcium phosphate or silica, indicating that not only the tip is under
      functional constraints requiring specific patterns of chemical heterogeneity. The
      complete absence of either silica or phosphate may be an additional feature with
      systematic relevance. Conclusions: This study demonstrates that complex, site
      specific and differential biomineralization is widespread across the order
      Boraginales. Calcium phosphate, only recently first reported as a structural
      plant biomineral, is common and appears to be functionally analogous to silica. A
      comparison with the phylogeny of Boraginales additionally reveals striking
      phylogenetic patterns. Most families show characteristic patterns of
      biomineralization, such as the virtual absence of calcium phosphate in Cordiaceae
      and Boraginaceae, the triple biomineralization of Heliotropiaceae and
      Ehretiaceae, or the absence of silica in Namaceae and Codonaceae. The complex
      chemical and phylogenetic patterns indicate that trichome evolution and
      functionalities are anything but simple and follow complex functional and
      phylogenetic constraints.

PMID- 29325009
TI  - Efficient generation of complete sequences of MDR-encoding plasmids by rapid
      assembly of MinION barcoding sequencing data.
AB  - Background: Multidrug resistance (MDR)-encoding plasmids are considered major
      molecular vehicles responsible for transmission of antibiotic resistance genes
      among bacteria of the same or different species. Delineating the complete
      sequences of such plasmids could provide valuable insight into the evolution and
      transmission mechanisms underlying bacterial antibiotic resistance development.
      However, due to the presence of multiple repeats of mobile elements, complete
      sequencing of MDR plasmids remains technically complicated, expensive, and time
      consuming. Results: Here, we demonstrate a rapid and efficient approach to
      obtaining multiple MDR plasmid sequences through the use of the MinION nanopore
      sequencing platform, which is incorporated in a portable device. By assembling
      the long sequencing reads generated by a single MinION run according to a rapid
      barcoding sequencing protocol, we obtained the complete sequences of 20 plasmids
      harbored by multiple bacterial strains. Importantly, single long reads covering a
      plasmid end-to-end were recorded, indicating that de novo assembly may be
      unnecessary if the single reads exhibit high accuracy. Conclusions: This workflow
      represents a convenient and cost-effective approach for systematic assessment of
      MDR plasmids responsible for treatment failure of bacterial infections, offering
      the opportunity to perform detailed molecular epidemiological studies to probe
      the evolutionary and transmission mechanisms of MDR-encoding elements.

PMID- 29325010
TI  - Incomplete Co-cladogenesis Between Zootermopsis Termites and Their Associated
      Protists.
AB  - Coevolution is a major driver of speciation in many host-associated symbionts. In
      the termite-protist digestive symbiosis, the protists are vertically inherited by
      anal feeding among nest mates. Lower termites (all termite families except
      Termitidae) and their symbionts have broadly co-diversified over ~170 million yr.
      However, this inference is based mainly on the restricted distribution of certain
      protist genera to certain termite families. With the exception of one study,
      which demonstrated congruent phylogenies for the protist Pseudotrichonympha and
      its Rhinotermitidae hosts, coevolution in this symbiosis has not been
      investigated with molecular methods. Here we have characterized the hindgut
      symbiotic protists (Phylum Parabasalia) across the genus Zootermopsis
      (Archotermopsidae) using single cell isolation, molecular phylogenetics, and high
      throughput amplicon sequencing. We report that the deepest divergence in the
      Zootermopsis phylogeny (Zootermopsis laticeps [Banks; Isoptera: Termopsidae])
      corresponds with a divergence in three of the hindgut protist species. However,
      the crown Zootermopsis taxa (Zootermopsis angusticollis [Hagen; Isoptera:
      Termopsidae], Z. nevadensis nevadensis [Hagen; Isoptera: Termopsidae], and Z.
      nevadensis nuttingi [Haverty & Thorne; Isoptera: Termopsidae]) share the same
      protist species, with no evidence of co-speciation under our methods. We
      interpret this pattern as incomplete co-cladogenesis, though the possibility of
      symbiont exchange cannot be entirely ruled out. This is the first molecular
      evidence that identical communities of termite-associated protist species can
      inhabit multiple distinct host species.

PMID- 29325011
TI  - Cognitive Complaints in Memory Clinic Patients and in Depressive Patients: An
      Interpretative Phenomenological Analysis.
AB  - Background and Objectives: Cognitive complaints are discussed as early signs of
      Alzheimer's disease (AD). However, they are also very common in cognitively
      normal older adults and in patients with depression. Qualitative, interview-based
      approaches might be useful to identify those features of cognitive complaints
      specific for the experiences of cognitive decline in preclinical or prodromal AD
      versus those complaints typically reported by depressed patients. Research Design
      and Methods: A semi-structured interview was administered to 21 cognitively
      normal older adults (HC), 18 nondemented memory clinic patients (MC), and 11
      patients with a major depression (MD), all above 55 years. Interpretative
      phenomenological analysis (IPA) was applied to the interview transcripts to
      develop emerging complaint themes in each group. To identify thematic
      correspondence and possibly novel, hitherto unappreciated themes, the extracted
      complaint categories were compared with the neurocognitive domains in the DSM-5
      and the content of the Everyday Cognition questionnaire (E-Cog). Results: IPA
      yielded 18 cognitive complaint categories in MC, 10 in depressive patients, and
      10 categories in the HC group. Several themes were common across groups, but some
      were group-specific, for example, spatial disorientation was only reported in MC
      patients. Some of these MC-specific themes were neither represented by DSM-5
      domains nor by the E-Cog. Discussion and Implications: We report a comprehensive
      qualitative description of cognitive complaints in old age which could help to
      develop questionnaires or structured interviews to better assess AD-related
      subjective cognitive decline. This may help to increase specificity in selecting
      high-risk subjects in research settings and improve clinical judgment of diverse
      cognitive complaints types mentioned by their patients.

PMID- 29325012
TI  - Systematic review of the cost-effectiveness of transcatheter interventions for
      valvular heart disease.
AB  - Transcatheter aortic valve implantation (TAVI) and transcatheter mitral valve
      repair (TMVR) are increasingly used for managing patients with valvular heart
      disease to whom surgery presents a high-risk. As these are costly procedures, a
      systematic review of studies concerned with their economic assessment was
      undertaken. The search was performed in PubMed and the Cochrane Library and
      followed recommended methodological steps. Studies were screened and their data
      were retrieved and were synthesized using a narrative approach. Twenty-four, good
      to high quality, evaluations were identified, representing different viewpoints,
      modelling techniques and willingness-to-pay thresholds. Studies show that in high
      risk patients with symptomatic aortic stenosis, TAVI may be cost-effective
      compared with medical management (MM) across many health care settings. In
      contrast, studies of TAVI compared with surgical aortic valve replacement (SAVR)
      yield conflicting and inconclusive results. The limited data available show that
      TMVR may also be cost-effective relative to MM in mitral valve disease. Existing
      evidence indicates that transcatheter techniques may be cost-effective options,
      relative to MM, in high-risk patients with valvular disease. Nonetheless, more
      research is needed to establish their economic value further, to investigate the
      drives of cost-effectiveness, and to evaluate surgical with transcatheter
      techniques in aortic valvular disease.

PMID- 29325013
TI  - Effects of Task Demands on Olfactory, Auditory, and Visual Event-Related
      Potentials Suggest Similar Top-Down Modulation Across Senses.
AB  - A widely held view is that top-down modulation of sensory information relies on
      an amodal control network that acts through the thalamus to regulate incoming
      signals. Olfaction lacks a direct thalamic projection, which suggests that it may
      differ from other modalities in this regard. We investigated the late positive
      complex (LPC) amplitudes of event-related potentials (ERP) from 28 participants,
      elicited by intensity-matched olfactory, auditory and visual stimuli, during a
      condition of focused attention, a neutral condition, and a condition in which
      stimuli were to be actively ignored. Amplitudes were largest during the attend
      condition, lowest during the ignore condition, with the neutral condition in
      between. A Bayesian analysis resulted in strong evidence for similar effects of
      task across sensory modalities. We conclude that olfaction, despite its unique
      neural projections, does not differ from audition and vision in terms of task
      dependent neural modulation of the LPC.

PMID- 29325014
TI  - CDKN1C (P57): one of the determinants of human endometrial stromal cell
      decidualization.
AB  - Decidualization is regulated by crosstalk of progesterone and the cAMP pathway.
      It involves extensive reprogramming of gene expression and includes a wide range
      of functions. To investigate how cell cycle regulatory genes drive the human
      endometrial stromal cell (ESC) exit cell cycle and enter differentiation, primary
      cultured ESC was treated with 8-Br-cAMP and MPA and cell cycle distribution was
      investigated by flow cytometry. High-throughput cell cycle regulatory gene
      expression was also studied by microarray. To validate the results of microarray
      chip, immunohistochemistry and semi-quantitative method of optical density were
      used to analyze the expression of cell cycle regulator proteins in proliferative
      phase of endometrium (n = 6) and early pregnancy decidua (n = 6). In addition, we
      selected cyclin-dependent kinase inhibitor 1c (CDKN1C, also known as P57) and
      cyclin-dependent kinase inhibitor 2b (CDKN2B, also known as P15) in order to
      study their role in the process of decidualization by the RNAi method. ESC was
      arrested at G0/G1 checkpoints during decidualization. Cell cycle regulatory genes
      P57 and P15 were upregulated, while cyclin D1 (CCND1), cyclin-dependent kinase 2
      (CDK2), and cell division cycle protein 2 homolog (CDC2) were downregulated
      during ESC differentiation both in vitro and vivo. P57 siRNA impaired ESC
      decidualization and caused different morphological and ultrastructural changes as
      well as a relatively low secretion of prolactin, but P15 siRNA had no effects. We
      concluded that P15, CCND1, CDK2, and CDC2 may participate in ESC withdraw from
      the cell cycle and go into differentiation both in vitro and in vivo. P57 is one
      of the key determinants of ESC differentiation due to its effect on the cell
      cycle distribution, but its association with the decidua-specific transcription
      factor needs further investigation.

PMID- 29325016
TI  - Single-procedure cure with atrial fibrillation ablation: may the 'force' be with
      you.

PMID- 29325015
TI  - Ecological mechanisms underlying soil bacterial responses to rainfall along a
      steep natural precipitation gradient.
AB  - Changes in the structure and function of soil microbial communities can drive
      substantial ecosystem feedbacks to altered precipitation. However, the ecological
      mechanisms underlying community responses to environmental change are not well
      understood. We used an 18-month soil reciprocal transplant experiment along a
      steep precipitation gradient to quantify how changes in rainfall affected
      bacterial community structure. We also conducted an enhanced dispersal treatment
      to ask whether higher immigration rates of taxa from the surrounding environment
      would accelerate community responses to climate change. Finally, we addressed how
      the composition of soil bacteria communities was related to the functional
      response of soil respiration to moisture in these treatments. Bacterial community
      structure (OTU abundance) and function (respiration rates) changed little in
      response to manipulation of either rainfall environment or dispersal rates.
      Although most bacteria were ecological generalists, a subset of specialist taxa,
      over 40% of which were Actinobacteria, tended to be more abundant in the rainfall
      environment that matched their original conditions. Bacteria community
      composition was an important predictor of the respiration response to moisture.
      Thus, the high compositional resistance of microbial communities dictated
      respiration responses to altered rainfall in this system.

PMID- 29325018
TI  - Corrigendum to: Training the next generation of cardiovascular leaders in health
      policy and economics.

PMID- 29325017
TI  - Cell-type-resolved alternative splicing patterns in mouse liver.
AB  - Alternative splicing (AS) is an important post-transcriptional regulatory
      mechanism to generate transcription diversity. However, the functional roles of
      AS in multiple cell types from one organ have not been reported. Here, we provide
      the most comprehensive profile for cell-type-resolved AS patterns in mouse liver.
      A total of 13,637 AS events are detected, representing 81.5% of all known AS
      events in the database. About 46.2% of multi-exon genes undergo AS from the four
      cell types of mouse liver: hepatocyte, liver sinusoidal endothelial cell, Kupffer
      cell and hepatic stellate cell, which regulates cell-specific functions and
      maintains cell characteristics. We also present a cell-type-specific splicing
      factors network in these four cell types of mouse liver, allowing data mining and
      generating knowledge to elucidate the roles of splicing factors in sustaining the
      cell-type-specialized AS profiles and functions. The splicing switching of Tak1
      gene between different cell types is firstly discovered and the specific Tak1
      isoform regulates hepatic cell-type-specific functions is verified. Thus, our
      work constructs a hepatic cell-specific splicing landscape and reveals the
      considerable contribution of AS to the cell type constitution and organ features.

PMID- 29325020
TI  - Dynamic Effects of Initial pH of Substrate on Biological Growth and Metamorphosis
      of Black Soldier Fly (Diptera: Stratiomyidae).
AB  - Edible insects have become a recognized alternative and sustainable source of
      high-quality proteins and fats for livestock or human consumption. In the
      production process of black soldier fly (BSF), (Hermetia illucens L. [Diptera:
      Stratiomyidae]), initial substrate pH is a critical parameter to ensure the best
      value of insect biomass, life history traits, and quality bio-fertilizer. This
      study examined the impact of initial pH values on BSF larvae production,
      development time, and adult longevity. The BSF were reared on artificial diet
      with initial pH of 2.0, 4.0, 6.0, 8.0, and 10.0; the control was set at 7.0.
      Final BSF larval weight was significantly greater in substrates having initial pH
      6.0 (0.21 g), control 7.0 (0.20 g), and 10.0 (0.20 g) with no significant
      difference among them, whereas larval weight reared with initial pH 2.0 and 4.0
      were lowest at 0.16 g (-23%). Prepupal weight was greatest when larvae were
      reared on substrates with initial pH 6.0 (0.18 g), control 7.0 (0.19 g), 8.0
      (0.18 g), and 10.0 (0.18 g). In contrast, the prepupal weight of larvae reared on
      diets with initial pH 2.0 was lowest at 0.15 g (-22%). Larval development time
      was 21.19 d at pH 8.0, about 3 d (12.5%) shorter than that of those reared on
      diets with initial pH 6.0, 7.0 control, and 10.0. In all treatments, pH shifted
      to 5.7 after 3-4 d and 8.5 after 16-17 d except for two groups (2.0 and 4.0)
      where the pH remained slightly acidic 5.0 and 6.5, respectively.

PMID- 29325019
TI  - Deep molecular phenotypes link complex disorders and physiological insult to CpG
      methylation.
AB  - Epigenetic regulation of cellular function provides a mechanism for rapid
      organismal adaptation to changes in health, lifestyle and environment.
      Associations of cytosine-guanine di-nucleotide (CpG) methylation with clinical
      endpoints that overlap with metabolic phenotypes suggest a regulatory role for
      these CpG sites in the body's response to disease or environmental stress. We
      previously identified 20 CpG sites in an epigenome-wide association study (EWAS)
      with metabolomics that were also associated in recent EWASs with diabetes-,
      obesity-, and smoking-related endpoints. To elucidate the molecular pathways that
      connect these potentially regulatory CpG sites to the associated disease or
      lifestyle factors, we conducted a multi-omics association study including 2474
      mass-spectrometry-based metabolites in plasma, urine and saliva, 225 NMR-based
      lipid and metabolite measures in blood, 1124 blood-circulating proteins using
      aptamer technology, 113 plasma protein N-glycans and 60 IgG-glyans, using 359
      samples from the multi-ethnic Qatar Metabolomics Study on Diabetes (QMDiab). We
      report 138 multi-omics associations at these CpG sites, including diabetes
      biomarkers at the diabetes-associated TXNIP locus, and smoking-specific
      metabolites and proteins at multiple smoking-associated loci, including AHRR.
      Mendelian randomization suggests a causal effect of metabolite levels on
      methylation of obesity-associated CpG sites, i.e. of glycerophospholipid PC(O-36:
      5), glycine and a very low-density lipoprotein (VLDL-A) on the methylation of the
      obesity-associated CpG loci DHCR24, MYO5C and CPT1A, respectively. Taken
      together, our study suggests that multi-omics-associated CpG methylation can
      provide functional read-outs for the underlying regulatory response mechanisms to
      disease or environmental insults.

PMID- 29325021
TI  - Oligonucleotides targeting TCF4 triplet repeat expansion inhibit RNA foci and mis
      splicing in Fuchs' dystrophy.
AB  - Fuchs' endothelial corneal dystrophy (FECD) is the most common repeat expansion
      disorder. FECD impacts 4% of U.S. population and is the leading indication for
      corneal transplantation. Most cases are caused by an expanded intronic CUG tract
      in the TCF4 gene that forms nuclear foci, sequesters splicing factors and impairs
      splicing. We investigated the sense and antisense RNA landscape at the FECD gene
      and find that the sense-expanded repeat transcript is the predominant species in
      patient corneas. In patient tissue, sense foci number were negatively correlated
      with age and showed no correlation with sex. Each endothelial cell has ~2 sense
      foci and each foci is single RNA molecule. We designed antisense oligonucleotides
      (ASOs) to target the mutant-repetitive RNA and demonstrated potent inhibition of
      foci in patient-derived cells. Ex vivo treatment of FECD human corneas
      effectively inhibits foci and reverses pathological changes in splicing. FECD has
      the potential to be a model for treating many trinucleotide repeat diseases and
      targeting the TCF4 expansion with ASOs represents a promising therapeutic
      strategy to prevent and treat FECD.

PMID- 29325022
TI  - Large-scale exome datasets reveal a new class of adaptor-related protein complex
      2 sigma subunit (AP2sigma) mutations, located at the interface with the AP2 alpha
      subunit, that impair calcium-sensing receptor signalling.
AB  - Mutations of the sigma subunit of the heterotetrameric adaptor-related protein
      complex 2 (AP2sigma) impair signalling of the calcium-sensing receptor (CaSR),
      and cause familial hypocalciuric hypercalcaemia type 3 (FHH3). To date, FHH3
      associated AP2sigma mutations have only been identified at one residue, Arg15. We
      hypothesized that additional rare AP2sigma variants may also be associated with
      altered CaSR function and hypercalcaemia, and sought for these by analysing >111
      995 exomes (>60 706 from ExAc and dbSNP, and 51 289 from the Geisinger Health
      System-Regeneron DiscovEHR dataset, which also contains clinical data). This
      identified 11 individuals to have 9 non-synonymous AP2sigma variants (Arg3His,
      Arg15His (x3), Ala44Thr, Phe52Tyr, Arg61His, Thr112Met, Met117Ile, Glu122Gly and
      Glu142Lys) with 3 of the 4 individuals who had Arg15His and Met117Ile AP2sigma
      variants having mild hypercalcaemia, thereby indicating a prevalence of FHH3
      associated AP2sigma mutations of ~7.8 per 100 000 individuals. Structural
      modelling of the novel eight AP2sigma variants (Arg3His, Ala44Thr, Phe52Tyr,
      Arg61His, Thr112Met, Met117Ile, Glu122Gly and Glu142Lys) predicted that the
      Arg3His, Thr112Met, Glu122Gly and Glu142Lys AP2sigma variants would disrupt polar
      contacts within the AP2sigma subunit or affect the interface between the AP2sigma
      and AP2alpha subunits. Functional analyses of all eight AP2sigma variants in CaSR
      expressing cells demonstrated that the Thr112Met, Met117Ile and Glu142Lys
      variants, located in the AP2sigma alpha4-alpha5 helical region that forms an
      interface with AP2alpha, impaired CaSR-mediated intracellular calcium (Cai2+)
      signalling, consistent with a loss of function, and this was rectified by
      treatment with the CaSR positive allosteric modulator cinacalcet. Thus, our
      studies demonstrate another potential class of FHH3-causing AP2sigma mutations
      located at the AP2sigma-AP2alpha interface.

PMID- 29325024
TI  - Genetic variants influencing phenotypic variance heterogeneity.
AB  - Most genetic studies identify genetic variants associated with disease risk or
      with the mean value of a quantitative trait. More rarely, genetic variants
      associated with variance heterogeneity are considered. In this study, we have
      identified such variance single-nucleotide polymorphisms (vSNPs) and examined if
      these represent biological gene * gene or gene * environment interactions or
      statistical artifacts caused by multiple linked genetic variants influencing the
      same phenotype. We have performed a genome-wide study, to identify vSNPs
      associated with variance heterogeneity in DNA methylation levels. Genotype data
      from over 10 million single-nucleotide polymorphisms (SNPs), and DNA methylation
      levels at over 430 000 CpG sites, were analyzed in 729 individuals. We identified
      vSNPs for 7195 CpG sites (P < 9.4 * 10-11). This is a relatively low number
      compared to 52 335 CpG sites for which SNPs were associated with mean DNA
      methylation levels. We further showed that variance heterogeneity between
      genotypes mainly represents additional, often rare, SNPs in linkage
      disequilibrium (LD) with the respective vSNP and for some vSNPs, multiple low
      frequency variants co-segregating with one of the vSNP alleles. Therefore, our
      results suggest that variance heterogeneity of DNA methylation mainly represents
      phenotypic effects by multiple SNPs, rather than biological interactions. Such
      effects may also be important for interpreting variance heterogeneity of more
      complex clinical phenotypes.

PMID- 29325026
TI  - Failure of sternal wires depends on the number of turns and plastic deformation:
      combined experimental and computational approach.
AB  - OBJECTIVES: The number of turns at the end of a wire closure is not described or
      discussed in any cardiosurgical guidelines. The hands-on experience of the
      surgeon plays a significant role. The aim of this work was to clarify the
      relationship between the number of turns of the suture and the resulting strength
      of the sternal fixation. METHODS: The study was performed in 2 independent steps.
      The first step was a finite element simulation, where the stress and strain
      distribution of the sternal fixation was observed. The second step included the
      experimental set-up and the statistical evaluation of the results. RESULTS: Our
      study showed that the failure force rose linearly as the number of turns
      increased. The lowest average measured force was 370 N (3 turns); the highest was
      430 N (7 turns). The failure modes were either untwisting of the wires or rupture
      of the closure, which is controlled by the number of turns. As the number of
      turns increases, superficial cracks can occur. CONCLUSIONS: Based on our results,
      the 5-turn option is the best solution for the closure. The failure force is
      still double the value reported in the literature, so there is a high safety
      margin for failure. The failure mode is untwisting; hence, no unexpected fracture
      can occur, and there is still an elastic core in the cross-section of the wire.

PMID- 29325027
TI  - Pathogens, microbiome and the host: emergence of the ecological Koch's
      postulates.
AB  - Even though tremendous progress has been made in the last decades to elucidate
      the mechanisms of intestinal homeostasis, dysbiosis and disease, we are only at
      the beginning of understanding the complexity of the gut ecosystem and the
      underlying interaction networks. We are also only starting to unravel the
      mechanisms that pathogens have evolved to overcome the barriers imposed by the
      microbiota and host to exploit the system to their own benefit. Recent work in
      these domains clearly indicates that the 'traditional Koch's postulates', which
      state that a given pathogen leads to a distinct disease, are not valid for all
      'infectious' diseases, but that a more complete and complex interpretation of
      Koch's postulates is needed in order to understand and explain them. This review
      summarises the current understanding of what defines a healthy gut ecosystem and
      highlights recent progress in uncovering the interplay between the host, its
      microbiota and invading intestinal pathogens. Based on these recent findings, we
      propose a new interpretation of Koch's postulates that we term 'ecological Koch's
      postulates'.

PMID- 29325025
TI  - Towards an understanding of resilience: responding to health systems shocks.
AB  - The recent outbreak of Ebola Virus Disease (EVD) in West Africa has drawn
      attention to the role and responsiveness of health systems in the face of shock.
      It brought into sharp focus the idea that health systems need not only to be
      stronger but also more 'resilient'. In this article, we argue that responding to
      shocks is an important aspect of resilience, examining the health system
      behaviour in the face of four types of contemporary shocks: the financial crisis
      in Europe from 2008 onwards; climate change disasters; the EVD outbreak in West
      Africa 2013-16; and the recent refugee and migration crisis in Europe. Based on
      this analysis, we identify '3 plus 2' critical dimensions of particular relevance
      to health systems' ability to adapt and respond to shocks; actions in all of
      these will determine the extent to which a response is successful. These are
      three core dimensions corresponding to three health systems functions: 'health
      information systems' (having the information and the knowledge to make a decision
      on what needs to be done); 'funding/financing mechanisms' (investing or
      mobilising resources to fund a response); and 'health workforce' (who should plan
      and implement it and how). These intersect with two cross-cutting aspects:
      'governance', as a fundamental function affecting all other system dimensions;
      and predominant 'values' shaping the response, and how it is experienced at
      individual and community levels. Moreover, across the crises examined here,
      integration within the health system contributed to resilience, as does
      connecting with local communities, evidenced by successful community responses to
      Ebola and social movements responding to the financial crisis. In all crises,
      inequalities grew, yet our evidence also highlights that the impact of shocks is
      amenable to government action. All these factors are shaped by context. We argue
      that the '3 plus 2' dimensions can inform pragmatic policies seeking to increase
      health systems resilience.

PMID- 29325028
TI  - TSH and FT4 Concentrations in Congenital Central Hypothyroidism and Mild
      Congenital Thyroidal Hypothyroidism.
AB  - Context: In central hypothyroidism (CeH), free thyroxine (FT4) concentrations are
      low, whereas thyrotropin (TSH) concentrations may be low, normal, or even
      slightly elevated due to reduced bioactivity. Congenital CeH (CCeH) may be
      isolated or part of multiple pituitary hormone deficiencies (MPHD). Objective: We
      tested our hypotheses that (1) TSH concentrations have a more U-shaped
      distribution in children with CCeH compared with children with a normally
      functioning hypothalamic-pituitary-thyroid axis and (2) TSH concentrations in
      children with CCeH with MPHD are higher compared with children with isolated
      CCeH. We also studied whether FT4 levels are helpful in distinguishing CCeH from
      mild congenital hypothyroidism of thyroidal origin (CH-T). Methods: Dutch
      neonatal screening TSH and first diagnostic TSH and FT4 were analyzed in all
      children diagnosed with permanent CCeH between 1995 and 2012. Controls were
      children with T4-binding globulin deficiency. FT4 concentrations in CCeH were
      compared with those in CH-T with TSH values in the same range as those of CCeH.
      Results: We studied 120 children with CCeH (isolated CCeH, n = 50; MPHD, n = 70)
      and 350 control subjects. Screening TSH concentrations were not significantly
      different (P = 0.055), but diagnostic TSH values were significantly different
      between the CCeH group and the control group (P = 0.037). TSH was significantly
      higher in MPHD compared with isolated CCeH (P = 0.004). FT4 concentrations were
      significantly lower in CCeH compared with mild CH-T (P < 0.0005). Conclusion: TSH
      values in CCeH have a more U-shaped distribution compared with controls with the
      highest TSH concentrations in MPHD. FT4 levels were significantly lower in CCeH
      compared with CH-T.

PMID- 29325029
TI  - Neuroconductor: an R platform for medical imaging analysis.
AB  - Neuroconductor (https://neuroconductor.org) is an open-source platform for rapid
      testing and dissemination of reproducible computational imaging software. The
      goals of the project are to: (i) provide a centralized repository of R software
      dedicated to image analysis, (ii) disseminate software updates quickly, (iii)
      train a large, diverse community of scientists using detailed tutorials and short
      courses, (iv) increase software quality via automatic and manual quality
      controls, and (v) promote reproducibility of image data analysis. Based on the
      programming language R (https://www.r-project.org/), Neuroconductor starts with
      51 inter-operable packages that cover multiple areas of imaging including
      visualization, data processing and storage, and statistical inference.
      Neuroconductor accepts new R package submissions, which are subject to a formal
      review and continuous automated testing. We provide a description of the purpose
      of Neuroconductor and the user and developer experience.

PMID- 29325023
TI  - The Extending Spectrum of NPC1-Related Human Disorders: From Niemann-Pick C1
      Disease to Obesity.
AB  - The Niemann-Pick type C1 (NPC1) protein regulates the transport of cholesterol
      and fatty acids from late endosomes/lysosomes and has a central role in
      maintaining lipid homeostasis. NPC1 loss-of-function mutations in humans cause
      NPC1 disease, a rare autosomal-recessive lipid-storage disorder characterized by
      progressive and lethal neurodegeneration, as well as liver and lung failure, due
      to cholesterol infiltration. In humans, genome-wide association studies and post
      genome-wide association studies highlight the implication of common variants in
      NPC1 in adult-onset obesity, body fat mass, and type 2 diabetes. Heterozygous
      human carriers of rare loss-of-function coding variants in NPC1 display an
      increased risk of morbid adult obesity. These associations have been confirmed in
      mice models, showing an important interaction with high-fat diet. In this review,
      we describe the current state of knowledge for NPC1 variants in relationship to
      pleiotropic effects on metabolism. We provide evidence that NPC1 gene variations
      may predispose to common metabolic diseases by modulating steroid hormone
      synthesis and/or lipid homeostasis. We also propose several important directions
      of research to further define the complex roles of NPC1 in metabolism. This
      review emphasizes the contribution of NPC1 to obesity and its metabolic
      complications.

PMID- 29325030
TI  - The effect of RNA substitution models on viroid and RNA virus phylogenies.
AB  - Many viroids and RNA viruses have genomes that exhibit secondary structure, with
      paired nucleotides forming stems and loops. Such structures violate a key
      assumption of most methods of phylogenetic reconstruction, that sequence change
      is independent among sites. However, phylogenetic analyses of these transmissible
      agents rarely use evolutionary models that account for RNA secondary structure.
      Here we assess the effect of using RNA-specific nucleotide substitution models on
      the phylogenetic inference of viroids and RNA viruses. We obtained data sets
      comprising full-genome nucleotide sequences from 6 viroid and 10 single-stranded
      RNA virus species. For each alignment, we inferred consensus RNA secondary
      structures, then evaluated different DNA and RNA substitution models. We used
      model selection to choose the best-fitting model and evaluate estimated Bayesian
      phylogenies. Further, for each data set we generated and compared Robinson-Foulds
      (RF) statistics in order to test whether the distributions of trees generated
      under alternative models are notably different to each other. In all alignments,
      the best-fitting model was one that considers RNA secondary structure: RNA models
      that allow a non-zero rate of double substitution (RNA16A, RNA16C) fitted best
      for both viral and viroid data sets. In 14 of 16 data sets, the use of an RNA
      specific model led to significantly longer tree lengths, but only in 3 cases did
      it have a significant effect on RFs. In conclusion, using RNA model when
      undertaking phylogenetic inference of viroids and RNA viruses can provide a
      better model fit than standard approaches and model choice can significantly
      affect branch length estimates.

PMID- 29325031
TI  - Use of deep whole-genome sequencing data to identify structure risk variants in
      breast cancer susceptibility genes.
AB  - Functional disruptions of susceptibility genes by large genomic structure variant
      (SV) deletions in germlines are known to be associated with cancer risk. However,
      few studies have been conducted to systematically search for SV deletions in
      breast cancer susceptibility genes. We analysed deep (> 30x) whole-genome
      sequencing (WGS) data generated in blood samples from 128 breast cancer patients
      of Asian and European descent with either a strong family history of breast
      cancer or early cancer onset disease. To identify SV deletions in known or
      suspected breast cancer susceptibility genes, we used multiple SV calling tools
      including Genome STRiP, Delly, Manta, BreakDancer and Pindel. SV deletions were
      detected by at least three of these bioinformatics tools in five genes.
      Specifically, we identified heterozygous deletions covering a fraction of the
      coding regions of BRCA1 (with approximately 80kb in two patients), and TP53 genes
      (with ~1.6 kb in two patients), and of intronic regions (~1 kb) of the PALB2 (one
      patient), PTEN (three patients) and RAD51C genes (one patient). We confirmed the
      presence of these deletions using real-time quantitative PCR (qPCR). Our study
      identified novel SV deletions in breast cancer susceptibility genes and the
      identification of such SV deletions may improve clinical testing.

PMID- 29325032
TI  - Effect of diazoxide on Friedreich ataxia models.
AB  - Friedreich ataxia (FRDA) is an inherited recessive disorder caused by a
      deficiency in the mitochondrial protein frataxin. There is currently no effective
      treatment for FRDA available, especially for neurological deficits. In this
      study, we tested diazoxide, a drug commonly used as vasodilator in the treatment
      of acute hypertension, on cellular and animal models of FRDA. We first showed
      that diazoxide increases frataxin protein levels in FRDA lymphoblastoid cell
      lines, via the mammalian target of rapamycin (mTOR) pathway. We then explored the
      potential therapeutic effect of diazoxide in frataxin-deficient transgenic YG8sR
      mice and we found that prolonged oral administration of 3 mpk/d diazoxide was
      found to be safe, but produced variable effects concerning efficacy. YG8sR mice
      showed improved beam walk coordination abilities and footprint stride patterns,
      but a generally reduced locomotor activity. Moreover, they showed significantly
      increased frataxin expression, improved aconitase activity, and decreased protein
      oxidation in cerebellum and brain mitochondrial tissue extracts. Further studies
      are needed before this drug should be considered for FRDA clinical trials.

PMID- 29325033
TI  - Cancer Risk in Older Persons Living With Human Immunodeficiency Virus Infection
      in the United States.
AB  - Background: Cancer risk is increased in persons living with human
      immunodeficiency virus (HIV) (PLWH). Improved survival has led to an aging of
      PLWH. We evaluated the cancer risk in older PLWH (age >=50 years). Methods: We
      included data from the HIV/AIDS Cancer Match Study (1996-2012) and evaluated
      risks of Kaposi sarcoma (KS), non-Hodgkin lymphoma (NHL), Hodgkin lymphoma, and
      cervical, anal, lung, liver, oral cavity/pharyngeal, breast, prostate, and colon
      cancers in older PLWH with risk in the general population by calculating
      standardized incidence ratios (SIRs) and excess absolute risks (EARs). Cancer
      risk by time since HIV diagnosis was estimated using Poisson regression. Results:
      We identified 10371 cancers among 183542 older PLWH. Risk was significantly
      increased for KS (SIR, 103.34), NHL (3.05), Hodgkin lymphoma (7.61), and cervical
      (2.02), anal (14.00), lung (1.71), liver (2.91), and oral cavity/pharyngeal
      (1.66) cancers, and reduced for breast (0.61), prostate (0.47), and colon (0.63)
      cancers. SIRs declined with age for all cancers; however, EARs increased with age
      for anal, lung, liver, and oral cavity/pharyngeal cancers. Cancer risk was
      highest for most cancers within 5 years after HIV diagnosis; risk decreased with
      increasing time since HIV diagnosis for KS, NHL, lung cancer, and Hodgkin
      lymphoma. Conclusions: Cancer risk is elevated among older PLWH. Although SIRs
      decrease with age, EARs are higher for some cancers, reflecting a greater
      absolute excess in cancer incidence among older PLWH. High risk in the first 5
      years after HIV diagnosis for some cancers highlights the need for early HIV
      diagnosis and rapid treatment initiation.

PMID- 29325034
TI  - Ghrelin Preserves Ischemia-Induced Vasodilation of Male Rat Coronary Vessels
      Following beta-Adrenergic Receptor Blockade.
AB  - Acute myocardial infarction (MI) triggers an adverse increase in cardiac
      sympathetic nerve activity (SNA). Whereas beta-adrenergic receptor (beta-AR)
      blockers are routinely used for the management of MI, they may also counter beta
      AR-mediated vasodilation of coronary vessels. We have reported that ghrelin
      prevents sympathetic activation following MI. Whether ghrelin modulates coronary
      vascular tone following MI, either through the modulation of SNA or directly as a
      vasoactive mediator, has never been addressed. We used synchrotron
      microangiography to image coronary perfusion and vessel internal diameter (ID) in
      anesthetized Sprague-Dawley rats, before and then again 30 minutes after
      induction of an MI (left coronary artery ligation). Rats were injected with
      either saline or ghrelin (150 ug/kg, subcutaneously), immediately following the
      MI or sham surgery. Coronary angiograms were also recorded following beta-AR
      blockade (propranolol, 2 mg/kg, intravenously). Finally, wire myography was used
      to assess the effect of ghrelin on vascular tone in isolated human internal
      mammary arteries (IMAs). Acute MI enhanced coronary perfusion to
      nonischemicregions through dilation of small arterioles (ID 50 to 250 um) and
      microvessel recruitment, irrespective of ghrelin treatment. In ghrelin-treated
      rats, beta-AR blockade did not alter the ischemia-induced vasodilation, yet in
      saline-treated rats, beta-AR blockade abolished the vasodilation of small
      arterioles. Finally, ghrelin caused a dose-dependent vasodilation of IMA rings
      (preconstricted with phenylephrine). In summary, this study highlights ghrelin as
      a promising adjunct therapy that can be used in combination with routine beta-AR
      blockade treatment for preserving coronary blood flow and cardiac performance in
      patients who suffer an acute MI.

PMID- 29325035
TI  - Amplicon-based next-generation sequencing of plasma cell-free DNA for detection
      of driver and resistance mutations in advanced non-small cell lung cancer.
AB  - Background: Genomic analysis of plasma cell-free DNA is transforming lung cancer
      care; however, available assays are limited by cost, turnaround time, and
      imperfect accuracy. Here, we study amplicon-based plasma next-generation
      sequencing (NGS), rather than hybrid-capture-based plasma NGS, hypothesizing this
      would allow sensitive detection and monitoring of driver and resistance mutations
      in advanced non-small cell lung cancer (NSCLC). Patients and methods: Plasma
      samples from patients with NSCLC and a known targetable genotype (EGFR, ALK/ROS1,
      and other rare genotypes) were collected while on therapy and analyzed blinded to
      tumor genotype. Plasma NGS was carried out using enhanced tagged amplicon
      sequencing of hotspots and coding regions from 36 genes, as well as intronic
      coverage for detection of ALK/ROS1 fusions. Diagnostic accuracy was compared with
      plasma droplet digital PCR (ddPCR) and tumor genotype. Results: A total of 168
      specimens from 46 patients were studied. Matched plasma NGS and ddPCR across 120
      variants from 80 samples revealed high concordance of allelic fraction (R2 =
      0.95). Pretreatment, sensitivity of plasma NGS for the detection of EGFR driver
      mutations was 100% (30/30), compared with 87% for ddPCR (26/30). A full spectrum
      of rare driver oncogenic mutations could be detected including sensitive
      detection of ALK/ROS1 fusions (8/9 detected, 89%). Studying 25 patients positive
      for EGFR T790M that developed resistance to osimertinib, 15 resistance mechanisms
      could be detected including tertiary EGFR mutations (C797S, Q791P) and mutations
      or amplifications of non-EGFR genes, some of which could be detected pretreatment
      or months before progression. Conclusions: This blinded analysis demonstrates the
      ability of amplicon-based plasma NGS to detect a full range of targetable
      genotypes in NSCLC, including fusion genes, with high accuracy. The ability of
      plasma NGS to detect a range of preexisting and acquired resistance mechanisms
      highlights its potential value as an alternative to single mutation digital PCR
      based plasma assays for personalizing treatment of TKI resistance in lung cancer.

PMID- 29325036
TI  - Evaluation of left atrial linear ablation using contiguous and optimized
      radiofrequency lesions: the ALINE study.
AB  - Aims: Achieving block across linear lesions is challenging. We prospectively
      evaluated radiofrequency (RF) linear ablation at the roof and mitral isthmus (MI)
      using point-by-point contiguous and optimized RF lesions. Methods and results:
      Forty-one consecutive patients with symptomatic persistent AF underwent stepwise
      contact force (CF)-guided catheter ablation during ongoing AF. A single linear
      set of RF lesions was delivered at the roof and posterior MI according to the
      'Atrial LINEar' (ALINE) criteria, i.e. point-by-point RF delivery (up to 35 W)
      respecting strict criteria of contiguity (inter-lesion distance <= 6 mm) and
      indirect lesion depth assessment (ablation index >=550). We assessed the
      incidence of bidirectional block across both lines only after restoration of
      sinus rhythm. After a median RF time of 7 min [interquartile range (IQR) 5-9],
      first-pass block across roof lines was observed in 38 of 41 (93%) patients. Final
      bidirectional roof block was achieved in 40 of 41 (98%) patients. First-pass
      block was observed in 8 of 35 (23%) MI lines, after a median RF time of 8 min
      (IQR 7-12). Additional endo- and epicardial (54% of patients) RF applications
      resulted in final bidirectional MI block in 28 of 35 (80%) patients. During a
      median follow-up of 396 (IQR 310-442) days, 12 patients underwent repeat
      procedures, with conduction recovery in 4 of 12 and 5 of 10 previously blocked
      roof lines and MI lines, respectively. No complications occurred. Conclusion:
      Anatomical linear ablation using contiguous and optimized RF lesions results in a
      high rate of first-pass block at the roof but not at the MI. Due to its complex
      3D architecture, the MI frequently requires additional endo- and epicardial RF
      lesions to be blocked.

PMID- 29325038
TI  - The CRISPR-Cas system in Enterobacteriaceae.
AB  - In nature, microorganisms are constantly exposed to multiple viral infections and
      thus have developed many strategies to survive phage attack and invasion by
      foreign DNA. One of such strategies is the clustered regularly interspaced short
      palindromic repeats (CRISPR)/CRISPR-associated proteins (Cas) bacterial
      immunological system. This defense mechanism is widespread in prokaryotes
      including several families such as Enterobacteriaceae. Much knowledge about the
      CRISPR-Cas system has been generated, including its biological functions,
      transcriptional regulation, distribution, utility as a molecular marker and as a
      tool for specific genome editing. This review focuses on these aspects and
      describes the state of the art of the CRISPR-Cas system in the Enterobacteriaceae
      bacterial family.

PMID- 29325039
TI  - The Stress Factor of Social Media.

PMID- 29325037
TI  - Mediator complex component MED13 regulates zygotic genome activation and is
      required for postimplantation development in the mouse.
AB  - Understanding factors that regulate zygotic genome activation (ZGA) is critical
      for determining how cells are reprogrammed to become totipotent or pluripotent.
      There is limited information regarding how this process occurs physiologically in
      early mammalian embryos. Here, we identify a mediator complex subunit, MED13, as
      translated during mouse oocyte maturation and transcribed early from the zygotic
      genome. Knockdown and conditional knockout approaches demonstrate that MED13 is
      essential for ZGA in the mouse, in part by regulating expression of the embryo
      specific chromatin remodeling complex, esBAF. The role of MED13 in ZGA is
      mediated in part by interactions with E2F transcription factors. In addition to
      MED13, its paralog, MED13L, is required for successful preimplantation embryo
      development. MED13L partially compensates for loss of MED13 function in
      preimplantation knockout embryos, but postimplantation development is not rescued
      by MED13L. Our data demonstrate an essential role for MED13 in supporting
      chromatin reprogramming and directed transcription of essential genes during ZGA.

PMID- 29325040
TI  - Phenotypic evaluation and characterization of 21 industrial Saccharomyces
      cerevisiae yeast strains.
AB  - Microorganisms have been studied and used extensively to produce value-added
      fuels and chemicals. Yeasts, specifically Saccharomyces cerevisiae, receive
      industrial attention because of their well-known ability to ferment glucose and
      produce ethanol. Thousands of natural or genetically modified S. cerevisiae have
      been found in industrial environments for various purposes. These industrial
      strains are isolated from industrial fermentation sites, and they are considered
      as potential host strains for superior fermentation processes. In many cases,
      industrial yeast strains have higher thermotolerance, increased resistances
      towards fermentation inhibitors and increased glucose fermentation rates under
      anaerobic conditions when compared with laboratory yeast strains. Despite the
      advantages of industrial strains, they are often not well characterized. Through
      screening and phenotypic characterization of commercially available industrial
      yeast strains, industrial fermentation processes requiring specific environmental
      conditions may be able to select an ideal starting yeast strain to be further
      engineered. Here, we have characterized and compared 21 industrial S. cerevisiae
      strains under multiple conditions, including their tolerance to varying pH
      conditions, resistance to fermentation inhibitors, sporulation efficiency and
      ability to ferment lignocellulosic sugars. These data may be useful for the
      selection of a parental strain for specific biotechnological applications of
      engineered yeast.

PMID- 29325041
TI  - Spontaneous massive hemothorax presenting as a late complication of stent
      implantation in a patient with pulmonary vein stenosis following radiofrequency
      ablation for atrial fibrillation.
AB  - Catheter ablation for symptomatic and drug-resistant atrial fibrillation is
      considered as the main acquired cause of pulmonary vein stenosis in adults.
      Controversy currently exists about the optimal treatment approach of this entity.
      Stenting seems to achieve lower vessel restenosis rates than isolated balloon
      angioplasty. However, these techniques are not exempt from complications. We
      present a case of spontaneous massive haemothorax presenting as a late
      complication of stent implantation in a patient with pulmonary vein stenosis.

PMID- 29325042
TI  - Biochemistry of complex glycan depolymerisation by the human gut microbiota.
AB  - The human gut microbiota (HGM) makes an important contribution to health and
      disease. It is a complex microbial community of trillions of microbes with a
      majority of its members represented within two phyla, the Bacteroidetes and
      Firmicutes, although it also contains species of Actinobacteria and
      Proteobacteria. Reflecting its importance, the HGM is sometimes referred to as an
      'organ' as it performs functions analogous to systemic tissues within the human
      host. The major nutrients available to the HGM are host and dietary complex
      carbohydrates. To utilise these nutrient sources, the HGM has developed
      elaborate, variable and sophisticated systems for the sensing, capture and
      utilisation of these glycans. Understanding nutrient acquisition by the HGM can
      thus provide mechanistic insights into the dynamics of this ecosystem, and how it
      impacts human health. Dietary nutrient sources include a wide variety of simple
      and complex plant and animal-derived glycans most of which are not degraded by
      enzymes in the digestive tract of the host. Here we review how various adaptive
      mechanisms that operate across the major phyla of the HGM contribute to glycan
      utilisation, focusing on the most complex carbohydrates presented to this
      ecosystem.

PMID- 29325043
TI  - RomA, A Periplasmic Protein Involved in the Synthesis of the Lipopolysaccharide,
      Tunes Down the Inflammatory Response Triggered by Brucella.
AB  - Brucellaceae are stealthy pathogens with the ability to survive and replicate in
      the host in the context of a strong immune response. This capacity relies on
      several virulence factors that are able to modulate the immune system and in
      their structural components that have low proinflammatory activities.
      Lipopolysaccharide (LPS), the main component of the outer membrane, is a central
      virulence factor of Brucella, and it has been well established that it induces a
      low inflammatory response. We describe here the identification and
      characterization of a novel periplasmic protein (RomA) conserved in alpha
      proteobacteria, which is involved in the homeostasis of the outer membrane. A
      mutant in this gene showed several phenotypes, such as membrane defects, altered
      LPS composition, reduced adhesion, and increased virulence and inflammation. We
      show that RomA is involved in the synthesis of LPS, probably coordinating part of
      the biosynthetic complex in the periplasm. Its absence alters the normal
      synthesis of this macromolecule and affects the homeostasis of the outer
      membrane, resulting in a strain with a hyperinflammatory phenotype. Our results
      suggest that the proper synthesis of LPS is central to maximize virulence and
      minimize inflammation.

PMID- 29325044
TI  - Adaptation of Staphylococcus aureus to Airway Environments in Patients With
      Cystic Fibrosis by Upregulation of Superoxide Dismutase M and Iron-Scavenging
      Proteins.
AB  - Adaptation of S. aureus to the hostile environment of CF airways resulted in
      changed abundance of proteins involved in energy metabolism, cellular processes,
      transport and binding, but most importantly in an iron-scavenging phenotype and
      increased activity of superoxide dismutase M.

PMID- 29325046
TI  - The rise of a new associationist school for lesion-symptom mapping.

PMID- 29325045
TI  - Mean High-Dose l-Thyroxine Treatment Is Efficient and Safe to Achieve a Normal IQ
      in Young Adult Patients With Congenital Hypothyroidism.
AB  - Context: The optimal levothyroxine (LT4) dose to treat congenital hypothyroidism
      (CH) remains unclear, with debate over whether higher starting doses (>10 ug/kg)
      are necessary and safe for a normal intelligence quotient (IQ). Objective: To
      examine psychomotor, metabolic, and quality of life (QoL) outcomes in patients
      with CH treated with a mean high initial LT4 dose. Design, settings,
      participants: A cross-sectional cohort study of patients with CH identified in
      the Berlin newborn screening program from 1979 to 2003; 76 patients with CH (mean
      age, 18 years; mean initial LT4 dose, 13.5 ug/kg) and 40 siblings completed the
      study. Main outcome measures: Psychomotor (Wechsler Intelligence Test, CNS Vital
      Signs), QoL (short form-36 Health Survey), anthropometric (body mass index,
      height), and metabolic (intima media thickness, laboratory parameters) outcomes
      were compared with those of healthy siblings. Mean values and percentage of
      episodes of elevated thyroxine (T4) and tri-jod-thyronin (T3) and suppressed
      thyrotropin (TSH) before age 2 years were analyzed. A meta-analysis of CH
      treatment studies was performed. Results: There were no significant differences
      in IQ, QoL, or other outcome measures in patients with CH compared with controls.
      Most T4 levels were high before age 2 years and during subsequent testing, but
      mean T3 and TSH levels remained normal. The meta-analysis showed a significant IQ
      difference in severe vs mild CH cases only when treatment started with an LT4
      dose <10 ug/kg. Conclusions: High initial LT4 dosing was effective and safely
      achieved optimal cognitive development in patients with CH, including those
      severely affected. Supranormal T4 values during infancy were not associated with
      impaired IQ in adolescence.

PMID- 29325047
TI  - Early nucleus basalis of Meynert degeneration predicts cognitive decline in
      Parkinson's disease.

PMID- 29325049
TI  - Spread of tau deposits: can we trust in vivo findings?

PMID- 29325048
TI  - Holding down the pain.

PMID- 29325050
TI  - Editorial.

PMID- 29325051
TI  - Dr Harrison Martland and the history of punch drunk syndrome.

PMID- 29325052
TI  - A MicroRNA Signature for Evaluation of Risk and Severity of Autoimmune Thyroid
      Diseases.
AB  - Context: Circulating microRNAs (miRNAs) are emerging as an interesting research
      area because of their potential role as novel biomarkers and therapeutic targets.
      Their involvement in autoimmune thyroid diseases (AITDs) has not been fully
      explored. Objective: To compare the expression profile of miRNAs in thyroid
      tissue from patients with AITD and controls, using next-generation sequencing,
      further validated our findings in thyroid and serum samples. Design: Twenty fresh
      frozen thyroid tissues (15 from patients with AITD and 5 from controls) were used
      for miRNA next-generation sequencing. Thirty-six thyroid samples were recruited
      for the qRT-PCR validation test and 58 serum samples for further validation in
      peripheral blood. Results: Expression of several miRNAs that had been previously
      associated with relevant immunological functions was significantly dysregulated.
      Specifically, eight differentially expressed miRNAs (miR-21-5p, miR-142-3p, miR
      146a-5p, miR-146b-5p, miR-155-5p, miR-338-5p, miR-342-5p, and miR-766-3p) were
      confirmed using qRT-PCR in thyroid samples, and three had the same behavior in
      tissue and serum samples (miR-21-5p, miR-142-3p, and miR-146a-5p). Furthermore,
      when the expression of these miRNAs was assessed together with five additional
      ones previously related to AITD in peripheral blood, the expression of five (miR
      Let7d-5p, miR-21-5p, miR-96-5p, miR-142-3p, and miR-301a-3p) was significantly
      expressed in AITD and, in patients with Graves disease (GD), was correlated with
      a higher severity of disease, including active ophthalmopathy, goiter, higher
      antibody titers, and/or higher recurrence rates. Conclusions: The present
      findings identify a serum five-signature miRNA that could be an independent risk
      factor for developing AITD and a predisposition of a worse clinical picture in
      patients with GD.

PMID- 29325053
TI  - Corrigendum to: Incidence and outcomes of emergent cardiac surgery during
      transfemoral transcatheter aortic valve implantation (TAVI): insights from the
      European Registry on Emergent Cardiac Surgery during TAVI (EuRECS-TAVI).

PMID- 29325054
TI  - Dehydration survival of crop plants and its measurement.
AB  - Dehydration survival under drought stress is defined in this review as the
      transition from plant activity into a quiescent state of life preservation, which
      will be terminated by either recovery or death, depending on the stress regime
      and the plant's resilience. Dehydration survival is a popular phenotype by which
      functional genomics attempts to test gene function in drought resistance and
      survival. The available reports on phenotyping and genotyping of dehydration
      survival in genomic studies indicate that the measurement of this trait is often
      biased to the extent that misguided interpretations are likely to occur. This
      review briefly discusses the physiological basis of dehydration survival in
      resurrection plants and crop plants, and concludes that in phenotyping
      dehydration survival there is a need to distinguish between dehydration avoidance
      and dehydration tolerance (also termed desiccation tolerance) in affecting
      survival and recovery. Without this distinction, functional genomics studies of
      the trait might be biased. Survival due to dehydration avoidance is expressed by
      the capacity to maintain a relatively high plant water status as the plant is
      desiccated. Survival due to dehydration tolerance is expressed by delayed
      mortality (mortality at a relatively low plant water status) as affected by the
      resilience of plant metabolism. The common test of dehydration survival, using
      the relative recovery after a given number of stress days, is therefore
      insufficient because it is mainly driven by dehydration avoidance and so ignores
      a possible role for dehydration tolerance. Conceivable methods for more accurate
      phenotyping of the two components of dehydration survival are proposed and
      discussed.

PMID- 29325055
TI  - Prevalence and Associated Risk Factors of Malaria in the First Trimester of
      Pregnancy: A Preconceptional Cohort Study in Benin.
AB  - Background: There is a lack of data on the burden of malaria in the first
      trimester of pregnancy in Africa, mainly because pregnant women generally attend
      the maternity clinic late. Bed nets are rarely provided to women before the
      second trimester of pregnancy and intermittent preventive treatment with
      sulfadoxine-pyrimethamine is not recommended before the second trimester, leaving
      women insufficiently or not protected in early pregnancy. Methods: To assess the
      burden of first trimester malaria, 387 women were followed up monthly from
      preconception to delivery. They were screened for malaria monthly from early
      pregnancy until delivery. A logistic multilevel model was used to assess maternal
      factors associated with malaria during the first trimester. Results: The
      proportion of women with at least 1 microscopic malaria infection during the
      first trimester of pregnancy was 20.8%. Women infected with malaria preconception
      were more likely to be infected during the first trimester (adjusted odds ratio:
      2.68; 95% confidence interval, 1.24-5.78). Early gestational age was also
      positively correlated with malaria infection. Conclusions: Using a
      preconceptional study design, we showed that malaria was highly prevalent in
      early pregnancy. This calls for the assessment of new strategies that could
      protect women as soon as the first trimester.

PMID- 29325056
TI  - Social health insurance schemes in Africa leave out the poor.

PMID- 29325057
TI  - Tumor purity quantification by clonal DNA methylation signatures.
AB  - Motivation: Controlling for tumor purity in molecular analyses is essential to
      allow for reliable genomic aberration calls, for inter-sample comparison and to
      monitor heterogeneity of cancer cell populations. In genome wide screening
      studies, the assessment of tumor purity is typically performed by means of
      computational methods that exploit somatic copy number aberrations. Results: We
      present a strategy, called Purity Assessment from clonal MEthylation Sites
      (PAMES), which uses the methylation level of a few dozen, highly clonal, tumor
      type specific CpG sites to estimate the purity of tumor samples, without the need
      of a matched benign control. We trained and validated our method in more than
      6000 samples from different datasets. Purity estimates by PAMES were highly
      concordant with other state-of-the-art tools and its evaluation in a cancer cell
      line dataset highlights its reliability to accurately estimate tumor admixtures.
      We extended the capability of PAMES to the analysis of CpG islands instead of the
      more platform-specific CpG sites and demonstrated its accuracy in a set of
      advanced tumors profiled by high throughput DNA methylation sequencing. These
      analyses show that PAMES is a valuable tool to assess the purity of tumor samples
      in the settings of clinical research and diagnostics. Availability and
      implementation: https://github.com/cgplab/PAMES. Contact:
      matteo.benelli@uslcentro.toscana.it or f.demichelis@unitn.it. Supplementary
      information: Supplementary data are available at Bioinformatics online.

PMID- 29325059
TI  - Aging in the Philippines.
AB  - The Philippines is a diverse country that will experience an increase in its
      aging population in the near future. The aim of this article is to provide an
      overview of the main issues surrounding population aging, as well as family
      caregiving and policies that are of concern to older adults in the Philippines.
      Policymakers and government leaders must plan for the expected growth in the
      numbers of older adults, which is likely to increase the demand for services and
      support for elders and their caregiving families. The Philippines' unique history
      and rich culture shapes its citizens' views on aging and bolsters expectations of
      informal caregiving for older family members. Research on aging in the
      Philippines and current policies must be enhanced to adequately address the needs
      of the country's aging citizens.

PMID- 29325058
TI  - Serum Carnitine Metabolites and Incident Type 2 Diabetes Mellitus in Patients
      With Suspected Stable Angina Pectoris.
AB  - Context: Carnitine and its metabolites are centrally involved in fatty acid
      metabolism. Although elevated circulating concentrations have been observed in
      obesity and insulin resistance, prospective studies examining whether these
      metabolites are associated with incident type 2 diabetes mellitus (T2D) are
      sparse. Objective: We performed a comprehensive evaluation of metabolites along
      the carnitine pathway relative to incident T2D. Design: A total of 2519 patients
      (73.1% men) with coronary artery disease, but without T2D, were followed for
      median 7.7 years until the end of 2009, during which 173 (6.9%) new cases of T2D
      were identified. Serum levels of free carnitine, its precursors trimethyllysine
      (TML) and gamma-butyrobetaine, and the esters acetyl-, propionyl-, (iso)valeryl-,
      octanoyl-, and palmitoylcarnitine were measured by liquid chromatography/tandem
      mass spectrometry. Risk associations were explored by logistic regression and
      reported per (log-transformed) standard deviation increment. Results: Median age
      at inclusion was 62 years and median body mass index (BMI) 26.0 kg/m2. In models
      adjusted for age, sex, fasting status, BMI, estimated glomerular filtration rate,
      glycated hemoglobin A1c, triglyceride and high-density lipoprotein cholesterol
      levels, and study center, serum levels of TML and palmitoylcarnitine associated
      positively [odds ratio (95% confidence interval), 1.22 (1.04 to 1.43) and 1.24
      (1.04 to 1.49), respectively], whereas gamma-butyrobetaine associated negatively
      [odds ratio (95% confidence interval) 0.81 (0.66 to 0.98)] with T2D risk.
      Conclusion: Serum levels of TML, gamma-butyrobetaine, and the long-chained
      palmitoylcarnitine predict long-term risk of T2D independently of traditional
      risk factors, possibly reflecting dysfunctional fatty acid metabolism in patients
      susceptible to T2D development.

PMID- 29325060
TI  - Pathophysiological analyses of leptomeningeal heterotopia using gyrencephalic
      mammals.
AB  - Leptomeningeal glioneuronal heterotopia (LGH) is a focal malformation of the
      cerebral cortex and frequently found in patients with thanatophoric dysplasia
      (TD). The pathophysiological mechanisms underlying LGH formation are still
      largely unclear because of difficulties in obtaining brain samples from human TD
      patients. Recently, we established a new animal model for analysing cortical
      malformations of human TD by utilizing our genetic manipulation technique for
      gyrencephalic carnivore ferrets. Here we investigated the pathophysiological
      mechanisms underlying the formation of LGH using our TD ferrets. We found that
      LGH was formed during corticogenesis in TD ferrets. Interestingly, we rarely
      found Ki-67-positive and phospho-histone H3-positive cells in LGH, suggesting
      that LGH formation does not involve cell proliferation. We uncovered that
      vimentin-positive radial glial fibers and doublecortin-positive migrating neurons
      were accumulated in LGH. This result may indicate that preferential cell
      migration into LGH underlies LGH formation. Our findings provide novel
      mechanistic insights into the pathogenesis of LGH in TD.

PMID- 29325061
TI  - Innovative strategies to improve adherence to non-vitamin K antagonist oral
      anticoagulants for stroke prevention in atrial fibrillation.

PMID- 29325062
TI  - ST-segment elevation myocardial infarction: the new ESC Guidelines.

PMID- 29325063
TI  - Epidemiology and Outcomes of Hematopoietic Stem Cell Transplantation in Human
      Immunodeficiency Virus-Positive Patients From 1998 to 2012: A Nationwide
      Analysis.
AB  - Background: Prior studies have shown that outcomes of hematopoietic stem cell
      transplantation (HSCT) in human immunodeficiency virus (HIV)-positive patients
      have been similar to outcomes in HIV-negative patients since effective
      implementation of highly active antiretroviral therapy by 1998, but they are
      limited by small sample size or noninclusion of recent data. Methods: We queried
      National Inpatient Sample, a large inpatient data set in the United States, from
      1998 to 2012 for HSCT, using the International Classification of Diseases, Ninth
      Revision, Clinical Modification (ICD-9-CM) procedure code 41.0. HIV-positive
      patients were identified by the presence of ICD-9-CM diagnostic codes 042, 043,
      044, V08, and 079.53. The primary outcome was in-hospital mortality rate, and the
      secondary outcome the in-hospital complication rate of HSCT. Outcomes were
      assessed by means of univariate, multivariate regression and matched-pair
      analysis. Results: A total of 39517 patients who underwent HSCT were identified.
      Among these, 108 patients had HIV infection. There were no differences in in
      hospital mortality rates or rates of intubation, sepsis, bacteremia, or graft-vs
      host disease between HIV-positive and HIV-negative patients after allogeneic or
      autologous HSCT. In allogeneic HSCT, HIV-positive patients had a significantly
      higher incidence of nontuberculous mycobacterial and cytomegalovirus infection
      than HIV-negative patients. Conclusion: Although HIV-positive patients may have a
      higher risk of certain opportunistic infections, they are not at higher risk of
      serious in-hospital complications of HSCT. Allogeneic and autologous HSCT can be
      safely performed in HIV-positive patients.

PMID- 29325064
TI  - Comparison of right ventricular function after ministernotomy and full sternotomy
      aortic valve replacement: a randomized study.
AB  - OBJECTIVES: Right ventricular (RV) function is impaired after cardiac surgery,
      possibly because of the opening of the pericardium. In minimally invasive aortic
      valve replacement, the pericardium is only partially incised. METHODS: A
      randomized trial compared RV function after ministernotomy versus full sternotomy
      in 40 adults undergoing aortic valve replacement at the Karolinska University
      Hospital. Primary outcomes were tricuspid annular plane systolic excursion, RV
      pulsed-wave tissue Doppler velocity, RV fractional area change and basal and mid
      RV transversal diameters on postoperative Days 4 and 40. RESULTS: On
      postoperative Day 4, the tricuspid annular plane systolic excursion had decreased
      in both groups [ministernotomy: median (Q1-Q3) 25 (21-28) vs 16 (11-18), P <
      0.001; sternotomy: 22.5 (22-22.5) vs 8 (7-12) mm, P < 0.001] but was higher in
      the ministernotomy group (P < 0.001). Pulsed-wave tissue Doppler RV velocity
      decreased significantly in patients who underwent sternotomy [10.5 (10-12) vs 6.5
      (5-8) cm/s, P < 0.001] but did not decrease significantly in patients who
      underwent ministernotomy [11.5 (11-12) vs 10 (9-11) cm/s, P = 0.054]. Fractional
      area change was equally decreased in both groups [ministernotomy: 46 (39-51) vs
      38 (34-44)%, P < 0.001; sternotomy: 45 (40-49) vs 37 (25-39.5)%, P = 0.003]. RV
      dimensions did not change on postoperative Day 4 in both groups. The differences
      between the 2 groups were similar 40 days postoperatively. CONCLUSIONS: RV long
      axis function was reduced after both ministernotomy and full sternotomy aortic
      valve replacement, but the reduction was more pronounced in the full sternotomy
      group. Global RV function was equally impaired in both groups postoperatively.
      Clinical trial registration: http://www.clinicaltrials.gov. Unique identifier:
      NCT01972555.

PMID- 29325065
TI  - Change in parental knowledge, attitudes and practice of antibiotic use after a
      national intervention programme.
AB  - Background: Nation-wide multifaceted interventions to improve antibiotic use were
      undertaken in the former Yugoslav Republic of Macedonia in September 2014. This
      study aimed to assess the parental knowledge and attitudes about antibiotics, and
      self-medication practices in children, and evaluate the impact of interventions
      on these parameters. Methods: Pre-post-intervention surveys were conducted in May
      2014-16 in three administrative regions in the country. Data were collected by
      interviewing parents of children younger than 15 years of age through a
      questionnaire. The analysis of knowledge, attitudes and antibiotic use involved
      descriptive quantitative statistics. The effects of interventions were assessed
      by a logistic and linear regression analysis. Results: Data from 1203
      interviewees showed that 80% of parents knew that antibiotics could kill
      bacteria, while 40% believed antibiotics could kill viruses. One third of parents
      expressed potential dissatisfaction with doctors who would not agree with them on
      antibiotic use. More parents received information about not taking antibiotics
      unnecessarily after the interventions, but the rates decreased one year later. At
      baseline, 20% of the parents and 10% of the children who received antibiotics in
      previous year, took them without prescriptions. Parental self-medication rates
      did not change over time, while children rates decreased only in 2015.
      Conclusion: The insignificant and short-term changes in knowledge, attitudes and
      self-medication demonstrate that interventions need to be implemented for a
      longer period of time, at a large scale, with active health providers'
      engagement, and accompanied by inspections to promote appropriate use of
      antibiotics and discourage self-medication.

PMID- 29325066
TI  - Toppar: an interactive browser for viewing association study results.
AB  - Summary: Data integration and visualization help geneticists make sense of large
      amounts of data. To help facilitate interpretation of genetic association data we
      developed Toppar, a customizable visualization tool that stores results from
      association studies and enables browsing over multiple results, by combining
      features from existing tools and linking to appropriate external databases.
      Availability and implementation: Detailed information on Toppar's features and
      functionality are on our website http://mccarthy.well.ox.ac.uk/toppar/docs along
      with instructions on how to download, install and run Toppar. Our online version
      of Toppar is accessible from the website and can be test-driven using Firefox,
      Safari or Chrome on sub-sets of publicly available genome-wide association study
      anthropometric waist and body mass index data (Locke et al., 2015; Shungin et
      al., 2015) from the Genetic Investigation of ANthropometric Traits consortium.
      Contact: totajuliusd@gmail.com.

PMID- 29325067
TI  - Cardiac rehabilitation in patients with acute coronary syndrome with primary
      percutaneous coronary intervention is associated with improved 10-year survival.
AB  - Aims: We aimed to assess the effects of a multidisciplinary cardiac
      rehabilitation (CR) program on survival after treatment with primary percutaneous
      coronary intervention (pPCI) for acute coronary syndrome (ACS). Methods and
      results: Using propensity matching analysis, a total of 1159 patients undergoing
      CR were 1:1 matched with ACS patients who did not undergo CR and survived at
      least 60 days. The Kaplan-Meier analyses and multivariate Cox regression analysis
      were applied to study differences in survival. During follow-up, a total of 335
      (14.5%) patients had died. Cumulative mortality rates at 5 and 10 years were 6.4%
      and 14.7% after CR and 10.4% and 23.5% in the no CR group (P < 0.001). Cardiac
      rehabilitation patients had 39% lower mortality than non-CR controls [10-year
      mortality 14.7% vs. 23.5%; adjusted hazard ratio (HR) 0.61; 95% confidence
      interval (CI) 0.46-0.81]. A total of 915 (78.9%) patients completed CR and had
      46% lower mortality than those who did not complete CR (10-year mortality 13.6%
      vs. 18.9%; adjusted HR 0.54; 95% CI 0.42-0.70). Conclusion: Patients who
      underwent pPCI for ACS, with a CR program had lower mortality than their non-CR
      counterparts. Mortality was particularly low in patients who completed the
      program. In conclusion, CR is still beneficial in terms of survival.

PMID- 29325068
TI  - Emergence of Nonfalciparum Plasmodium Infection Despite Regular Artemisinin
      Combination Therapy in an 18-Month Longitudinal Study of Ugandan Children and
      Their Mothers.
AB  - As part of a longitudinal cohort investigation of intestinal schistosomiasis and
      malaria in Ugandan children and their mothers on the shorelines of Lakes Victoria
      and Albert, we documented risk factors and morbidity associated with
      nonfalciparum Plasmodium infections and the longitudinal dynamics of Plasmodium
      species in children. Host age, household location, and Plasmodium falciparum
      infection were strongly associated with nonfalciparum Plasmodium infections, and
      Plasmodium malariae infection was associated with splenomegaly. Despite regular
      artemisinin combination therapy treatment, there was a 3-fold rise in P. malariae
      prevalence, which was not accountable for by increasing age of the child.
      Worryingly, our findings reveal the consistent emergence of nonfalciparum
      infections in children, highlighting the complex dynamics underlying multispecies
      infections here. Given the growing body of evidence that nonfalciparum malaria
      infections cause significant morbidity, we encourage better surveillance for
      nonfalciparum Plasmodium infections, particularly in children, with more
      sensitive DNA detection methods and improved field-based diagnostics.

PMID- 29325069
TI  - Effect of healthcare spending on the relationship between the Human Development
      Index and maternal and neonatal mortality.
AB  - Background: Several factors affect morbidity and mortality the world over.
      Previous research shows mortality rates are higher among individuals of lower
      socio-economic status. We investigated the trajectory of neonatal (NM) and
      maternal (MM) mortality between 2010 and 2014 and the effect of healthcare
      spending on the relationship between the Human Development Index (HDI) and NM and
      MM. Methods: Data were obtained from the United Nations Development Program and
      World Bank. Latent growth curve models (LGCMs) were estimated to determine the
      trajectory of NM and MM across the study period and the effect of the HDI on NM
      and MM. Mediation analysis was used to determine if healthcare expenditure
      mediated the relationship between HDI and NM and MM rates. ArcGIS (Esri,
      Redlands, CA, USA) was used to generate a choropleth map of changes in NM and MM
      between 2010 and 2014. Findings: Results showed many countries in Africa enjoyed
      decreases in NM and MM between 2010 and 2014, but other countries (Algeria, Libya
      and Sudan) showed little or no improvement. The LGCM for NM (Comparative Fit
      Index=0.956) and MM (CFI=0.963) demonstrated good fit to the data and showed that
      the HDI was negatively related to NM and MM. Mediation analysis showed that
      healthcare spending mediated the relationship between NM and MM in each year.
      Conclusions: Given that healthcare spending can mediate the relationship between
      HDI and NM and MM, increases in healthcare spending among countries with low HDI
      could improve NM and MM outcomes.

PMID- 29325070
TI  - Modification of the Association Between T-Cell Immune Responses and Human
      Immunodeficiency Virus Type 1 Infection Risk by Vaccine-Induced Antibody
      Responses in the HVTN 505 Trial.
AB  - Background: HVTN 505 was a human immunodeficiency virus type 1 (HIV-1) preventive
      vaccine efficacy trial of a DNA/recombinant adenovirus serotype 5 (rAd5) vaccine
      regimen. We assessed antibody responses measured 1 month after final vaccination
      (month 7) as correlates of HIV-1 acquisition risk. Methods: Binding antibody
      responses were quantified in serum samples from 25 primary endpoint vaccine cases
      (diagnosed with HIV-1 infection between month 7 and month 24) and 125 randomly
      sampled frequency-matched vaccine controls (HIV-1 negative at month 24). We
      prespecified for a primary analysis tier 6 antibody response biomarkers that
      measure immunoglobulin G (IgG) and immunoglobulin A (IgA) binding to Env proteins
      and 2 previously assessed T-cell response biomarkers. Results: Envelope-specific
      IgG responses were significantly correlated with decreased HIV-1 risk. Moreover,
      the interaction of IgG responses and Env-specific CD8+ T-cell polyfunctionality
      score had a highly significant association with HIV-1 risk after adjustment for
      multiple comparisons. Conclusions: Vaccinees with higher levels of Env IgG have
      significantly decreased HIV-1 risk when CD8+ T-cell responses are low. Moreover,
      vaccinees with high CD8+ T-cell responses generally have low risk, and those with
      low CD8+ T-cell and low Env antibody responses have high risk. These findings
      suggest the critical importance of inducing a robust IgG Env response when the
      CD8+ T-cell response is low.

PMID- 29325071
TI  - Viral suppressors of RNAi employ a rapid screening mode to discriminate viral RNA
      from cellular small RNA.
AB  - RNA interference (RNAi) is an indispensable mechanism for antiviral defense in
      insects, including mosquitoes that transmit human diseases. To escape this
      antiviral defense system, viruses encode suppressors of RNAi that prevent
      elimination of viral RNAs, and thus ensure efficient virus accumulation. Although
      the first animal Viral Suppressor of RNAi (VSR) was identified more than a decade
      ago, the molecular basis of RNAi suppression by these viral proteins remains
      unclear. Here, we developed a single-molecule fluorescence assay to investigate
      how VSRs inhibit the recognition of viral RNAs by Dcr-2, a key endoribonuclease
      enzyme in the RNAi pathway. Using VSRs from three insect RNA viruses (Culex Y
      virus, Drosophila X virus and Drosophila C virus), we reveal bimodal physical
      interactions between RNA molecules and VSRs. During initial interactions, these
      VSRs rapidly discriminate short RNA substrates from long dsRNA. VSRs engage
      nearly irreversible binding with long dsRNAs, thereby shielding it from
      recognition by Dcr-2. We propose that the length-dependent switch from rapid
      screening to irreversible binding reflects the main mechanism by which VSRs
      distinguish viral dsRNA from cellular RNA species such as microRNAs.

PMID- 29325073
TI  - The Women's Health Diagnostic Gap.
AB  - Pregnancy remains a significant health risk to women in both developed and
      underdeveloped countries. Worldwide, 10 to 20 million women have pregnancy
      complications including ectopic pregnancy, preterm birth, gestational diabetes
      mellitus, and hypertensive states, including preeclampsia. Despite advancements
      in women's health research, there is a large gap in the diagnostic tools
      available to screen, diagnose, and monitor these conditions. Herein, we examine
      existing diagnostic tools, such as the human chorionic gonadotropin
      discriminatory zone, cervicovaginal fetal fibronectin, sFlt-1:PlGF ratio, and
      glucose tolerance testing. We suggest specific objectives to improve diagnostic
      testing during pregnancy, including (1) developing high-quality biospecimen
      banks; (2) educating professionals on performance characteristics of screening
      tests for low prevalence diseases; (3) funding studies that address diseases
      unique to pregnancy; and (4) establishing trimester-specific reference intervals.
      Meeting these objectives could begin to narrow the diagnostic gap in women's
      health.

PMID- 29325072
TI  - Sensitive and specific post-call filtering of genetic variants in xenograft and
      primary tumors.
AB  - Motivation: Tumor genome sequencing offers great promise for guiding research and
      therapy, but spurious variant calls can arise from multiple sources. Mouse
      contamination can generate many spurious calls when sequencing patient-derived
      xenografts. Paralogous genome sequences can also generate spurious calls when
      sequencing any tumor. We developed a BLAST-based algorithm, Mouse And Paralog
      EXterminator (MAPEX), to identify and filter out spurious calls from both these
      sources. Results: When calling variants from xenografts, MAPEX has similar
      sensitivity and specificity to more complex algorithms. When applied to any
      tumor, MAPEX also automatically flags calls that potentially arise from
      paralogous sequences. Our implementation, mapexr, runs quickly and easily on a
      desktop computer. MAPEX is thus a useful addition to almost any pipeline for
      calling genetic variants in tumors. Availability and implementation: The mapexr
      package for R is available at https://github.com/bmannakee/mapexr under the MIT
      license. Contact: mannakee@email.arizona.edu or rgutenk@email.arizona.edu or
      eknudsen@email.arizona.edu. Supplementary information: Supplementary data are
      available at Bioinformatics online.

PMID- 29325074
TI  - Cervical Disc Arthroplasty: Current Evidence and Real-World Application.
AB  - Cervical total disc replacement (cTDR) is still considered a developing
      technology, with widespread clinical use beginning in the early 2000s. Despite
      being relatively new to the marketplace, the literature surrounding cTDR is
      abundant. We conducted a thorough review of literature published in the United
      States (US) and outside the US to report the current global state of cTDR
      research and clinical use. Search criteria were restricted to publications with a
      clinical patient population, excluding finite element analyses, biomechanical
      studies, cadaver studies, surgical technique-specific papers, and case studies.
      US publications mostly encompass the results of the highly controlled Food and
      Drug Administration Investigational Device Exemption trials. The predominantly
      level I evidence in the US literature supports the use of cTDR at 1 and 2
      surgical levels when compared to anterior cervical discectomy and fusion. In
      general, the outside the US studies typically have smaller patient populations,
      are rarely controlled, and include broader surgical indications. Though these
      studies are of lower levels of evidence, they serve to advance patient
      indications in the use of cTDR. Complications such as secondary surgery,
      heterotopic ossification, and adjacent segment degeneration also remain a focus
      of studies. Other external challenges facing cTDR technology include regulatory
      restrictions and health economics, both of which are beginning to be addressed.
      Combined, the evidence for cTDR is robust supporting a variety of clinical
      indications.

PMID- 29325079
TI  - Cardiovascular conditions predisposing to infective endocarditis: time to
      reconsider the current risk classification system?

PMID- 29325077
TI  - Integrating restriction site-associated DNA sequencing (RAD-seq) with
      morphological cladistic analysis clarifies evolutionary relationships among major
      species groups of bee orchids.
AB  - Background and Aims: Bee orchids (Ophrys) have become the most popular model
      system for studying reproduction via insect-mediated pseudo-copulation and for
      exploring the consequent, putatively adaptive, evolutionary radiations. However,
      despite intensive past research, both the phylogenetic structure and species
      diversity within the genus remain highly contentious. Here, we integrate next
      generation sequencing and morphological cladistic techniques to clarify the
      phylogeny of the genus. Methods: At least two accessions of each of the ten
      species groups previously circumscribed from large-scale cloned nuclear ribosomal
      internal transcibed spacer (nrITS) sequencing were subjected to restriction site
      associated sequencing (RAD-seq). The resulting matrix of 4159 single nucleotide
      polymorphisms (SNPs) for 34 accessions was used to construct an unrooted network
      and a rooted maximum likelihood phylogeny. A parallel morphological cladistic
      matrix of 43 characters generated both polymorphic and non-polymorphic sets of
      parsimony trees before being mapped across the RAD-seq topology. Key Results: RAD
      seq data strongly support the monophyly of nine out of ten groups previously
      circumscribed using nrITS and resolve three major clades; in contrast, supposed
      microspecies are barely distinguishable. Strong incongruence separated the RAD
      seq trees from both the morphological trees and traditional classifications;
      mapping of the morphological characters across the RAD-seq topology rendered them
      far more homoplastic. Conclusions: The comparatively high level of morphological
      homoplasy reflects extensive convergence, whereas the derived placement of the
      fusca group is attributed to paedomorphic simplification. The phenotype of the
      most recent common ancestor of the extant lineages is inferred, but it post-dates
      the majority of the character-state changes that typify the genus. RAD-seq may
      represent the high-water mark of the contribution of molecular phylogenetics to
      understanding evolution within Ophrys; further progress will require large-scale
      population-level studies that integrate phenotypic and genotypic data in a cogent
      conceptual framework.

PMID- 29325078
TI  - Genomic basis of recombination suppression in the hybrid between Caenorhabditis
      briggsae and C. nigoni.
AB  - DNA recombination is required for effective segregation and diversification of
      genomes and for the successful completion of meiosis. Recent studies in various
      species hybrids have demonstrated a genetic link between DNA recombination and
      speciation. Consistent with this, we observed a striking suppression of
      recombination in the hybrids between two nematodes, the hermaphroditic
      Caenorhabditis briggsae and the gonochoristic C. nigoni. To unravel the molecular
      basis underlying the recombination suppression in their hybrids, we generated a
      C. nigoni genome with chromosome-level contiguity and produced an improved C.
      briggsae genome with resolved gaps up to 2.8 Mb. The genome alignment reveals not
      only high sequence divergences but also pervasive intra- and inter-chromosomal
      sequence re-arrangements between the two species, which are plausible culprits
      for the observed suppression. Comparison of recombination boundary sequences
      suggests that recombination in the hybrid requires extensive sequence homology,
      which is rarely seen between the two genomes. The new genomes and genomic
      libraries form invaluable resources for studying genome evolution, hybrid
      incompatibilities and sex evolution for this pair of model species.

PMID- 29325080
TI  - DST659 genotype of Candida albicans showing positive association between biofilm
      formation and dominance in Taiwan.
AB  - Based on multiple locus sequence typing, we previously found that DST659 and
      DST693 were dominant genotypes of Candida albicans among the bloodstream isolates
      at Chang-Gung Memorial Hospital at Linkou. Biofilm-forming activity, which is
      critical for C. albicans virulence, probably contributed to the dominance of
      antifungal sensitive isolates in hospital. Both in vitro membrane weighting and
      in vivo zebrafish egg infection assays were used to evaluate the biofilm-forming
      activity of DST659 and DST693 genotypes. Medical records of the patients infected
      by these two genotypes were retrospectively reviewed. High biofilm-forming
      activity of DST659 isolates was demonstrated in vitro and further proved with the
      zebrafish egg infection model, which showed a positive correlation between the
      biofilm-forming extent on chorion and the in vitro biofilm activity. Moreover,
      significantly less embryos survived when infected with DST659 isolates than those
      with DST693 (1.25% vs. 11.43%), and the high-biofilm subset of DST659 showed a
      greater reduction in survival of embryos at 48 h post-infection than the low
      biofilm subset (0 vs. 1.92%). Patients infected with DST659 seemed to survive
      slightly worse than those infected with DST693, although the difference was
      insignificant. It is noteworthy that DST659-infected patients were associated
      with a higher incidence in renal insufficiency as compared to those with DST693,
      the low biofilm genotype. We suggest that a strong biofilm activity of DST659
      contributed to a high mortality rate in zebrafish hosts and poor renal function
      in patients, as well as gaining the dominance in the northern Taiwan.

PMID- 29325082
TI  - Growth Parameters, Effect Measure Modification and the Association Between
      Vaccination and Early Childhood Hospitalization With Non-targeted Infections.

PMID- 29325081
TI  - Dissatisfaction with current integration reforms of health insurance schemes in
      China: are they a success and what matters?
AB  - Integration reforms have been piloted as key policies to address the fragmented
      health insurance system in China. They are also regarded as a better choice for
      realizing a Universal Basic Medical Insurance System (UBMIS). This study has
      attempted to explore the determinants that may affect respondents'
      dissatisfaction with the reforms. The aim is to provide evidence for more
      effective policy adjustment during the next round of nationwide integration
      reforms in China. A cross-sectional questionnaire survey was conducted in Ningbo,
      Chongqing and Heilongjiang from 2014 to 2015. A stratified cluster sampling
      method was adopted. A total of 1644 respondents, working in units related to
      health insurance, were selected. A multivariate logistic regression model was
      employed to identify any association between dissatisfaction and the features of
      the ongoing integration reforms of health insurance schemes. Overall, about 47.6%
      of the respondents reported dissatisfaction with the ongoing integration reforms.
      This high level of dissatisfaction was found to be associated with ineffective
      outcomes of the integration reforms in achieving management system improvement
      [odds ratio (OR) = 1.846], inequity reduction (OR = 1.464) and actual coverage
      expansion (OR = 1.350), as perceived by the respondents. Those who were satisfied
      with the previously separated health insurance schemes (OR = 0.643), and those
      who preferred other policy options for achieving a UBMIS (OR = 1.471) were more
      likely to report dissatisfaction with the current reforms. Higher expectations of
      the risk-pooling level (with ORs ranging from 1.361 to 1.661) also significantly
      contributed to dissatisfaction. Health insurance managers in China have
      conflicting opinions about the performance of piloted integration reforms. Many
      believe that these reforms have failed significantly to improve the management
      systems, narrow inequity and expand actual benefit coverage. Various strategies
      should be undertaken in order to address these issues, such as clarifying the
      administrative institution behind the merged schemes at the central level,
      unifying the insurance information network, developing consistent policies and
      bridging the differences in benefits among schemes and regions.

PMID- 29325083
TI  - Reply to Burgner, et al.

PMID- 29325086
TI  - A 60-Year-Old Man With Fever and Headache After a Near-Drowning Event.

PMID- 29325084
TI  - Metformin Use Reverses the Increased Mortality Associated With Diabetes Mellitus
      During Tuberculosis Treatment.
AB  - Background: The global type 2 diabetes mellitus (DM) epidemic threatens progress
      made in reducing tuberculosis (TB)-related mortality worldwide. Previous clinical
      studies have not fully evaluated potential confounding variables in addressing
      the impact of DM on TB treatment outcomes. The antidiabetic agent metformin
      regulates autophagy and may play a role as a host-directed therapeutic adjuvant
      to antitubercular treatment. Methods: We conducted a retrospective cohort study
      comprising patients aged >=13 years undergoing treatment for culture-confirmed,
      drug-susceptible pulmonary TB. We assessed the effect of DM on mortality during
      TB treatment and 2-month TB sputum-culture conversion. We also evaluated the
      effect of metformin use on survival during TB treatment. Results: Among 2416
      patients undergoing TB treatment, after adjusting for age, sex, chronic kidney
      disease, cancer, hepatitis C, tobacco use, cavitary disease, and treatment
      adherence, patients with DM had 1.91 times higher odds (95% confidence interval
      [CI], 1.51-2.40) of death during TB treatment than patients without DM, and 1.72
      (95% CI, 1.25-2.38) times higher odds of remaining culture-positive at 2 months.
      Metformin use in patients with DM was significantly associated with decreased
      mortality during TB treatment (hazard ratio, 0.56 [95% CI, .39-.82]), and
      metformin users had similar mortality as patients without DM. Conclusions: This
      study suggests that despite multiple potential confounding variables, DM poses an
      increased risk of adverse TB treatment outcomes. There was a significant
      association between metformin use and decreased mortality during TB treatment,
      suggesting a potential role for this agent as adjunctive, host-directed therapy.

PMID- 29325087
TI  - A 60-Year-Old Man With Fever and Headache After a Near-Drowning Event.

PMID- 29325088
TI  - The comet assay: ready for 30 more years.
AB  - During the last 30 years, the comet assay has become widely used for the
      measurement of DNA damage and repair in cells and tissues. A landmark achievement
      was reached in 2016 when the Organization for Economic Co-operation and
      Development adopted a comet assay guideline for in vivo testing of DNA strand
      breaks in animals. However, the comet assay has much more to offer than being an
      assay for testing DNA strand breaks in animal organs. The use of repair enzymes
      increases the range of DNA lesions that can be detected with the assay. It can
      also be modified to measure DNA repair activity. Still, despite the long-term use
      of the assay, there is a need for studies that assess the impact of variation in
      specific steps of the procedure. This is particularly important for the on-going
      efforts to decrease the variation between experiments and laboratories. The
      articles in this Special Issue of Mutagenesis cover important technical issues of
      the comet assay procedure, nanogenotoxicity and ionising radiation sensitivity on
      plant cells. The included biomonitoring studies have assessed seasonal variation
      and certain predictors for the basal level of DNA damage in white blood cells.
      Lastly, the comet assay has been used in studies on genotoxicity of environmental
      and occupational exposures in human biomonitoring studies and animal models.
      Overall, the articles in this Special Issue demonstrate the versatility of the
      comet assay and they hold promise that the assay is ready for the next 30 years.

PMID- 29325089
TI  - Trends and results of lung cancer surgery in Finland between 2004 and 2014.
AB  - OBJECTIVES: The aim of this study was to investigate the current trends and
      results of lung cancer surgery in Finland at the population level. METHODS: Three
      compulsory national registries provided the data on surgical treatment of lung
      cancer during 2004 and 2014. Outcomes of interest were all-cause mortality,
      population level surgical rates and frequencies of resections. The data were
      divided into 2 eras to analyse changes in treatment strategies and baseline
      characteristics: 2004-2009 and 2010-2014. RESULTS: A total of 3621 patients
      underwent lung resections for cancer during the study period. The mean age of the
      patients was 65.8 years. During the study period, the patients were older and
      Charlson comorbidity index score of the patients increased (P < 0.001 for both).
      Simultaneously, the rate of surgery (from 12.8% to 14.4%, P = 0.001) and the rate
      of video-assisted thoracoscopic surgery increased (from 7.3% to 31.9%, P <
      0.001). The rate of pneumonectomy decreased from 12.7% to 7.5% (P < 0.001).
      Mortality was 2.3% at 30 days and 4.3% at 90 days without significant differences
      between eras. Overall survival was 85% at 1 year and 50.2% at 5 years. Long-term
      survival improved significantly during the study from 53% to 60.1% at 4 years (P
      < 0.001). CONCLUSIONS: This nationwide population-based study demonstrates an
      improvement in long-term outcome after lung cancer surgery despite an increasing
      age and comorbidity burden concomitantly with an increasing rate of surgery. This
      suggests that video-assisted thoracoscopic surgery can be offered to more
      patients with more comorbidities while still improving lung cancer survival.

PMID- 29325090
TI  - The 5 Ws of a gluten challenge for gluten-related disorders.
AB  - Gluten-related disorders (GRDs) are gradually emerging as epidemiologically
      relevant diseases, with a global prevalence estimated to be approximately 5% in
      the population. Conditions related to gluten ingestion include celiac disease
      (CD), wheat allergy (WA), and nonceliac gluten sensitivity (NCGS). Although
      mediated by different pathogenic pathways, these 3 conditions share similar
      clinical manifestations and can present a difficult differential diagnosis. The
      gluten challenge (GC) is an important diagnostic tool for GRDs, but there is
      great variability in regards to deciding which patients should be challenged,
      what amount of gluten should be used, what the GC duration should be, when and
      where the GC should occur, and, sometimes, why to conduct a GC. This review
      summarizes the current knowledge about the desirable characteristics of GCs in
      the 3 main GRDs following a 5 Ws approach-that is, the 5 main journalistic
      questions: who, what, when, where, why. The answers will help to determine the
      correct use of the GC in diagnosing GRDs.

PMID- 29325091
TI  - alpha-secretase ADAM10 physically interacts with beta-secretase BACE1 in neurons
      and regulates CHL1 proteolysis.
AB  - alpha-secretase and beta-secretase are known to compete for amyloid precursor
      protein (APP) processing and thus play a vital role in Alzheimer's disease
      pathogenesis. A disintegrin and metalloproteinase 10 (ADAM10) and beta-site APP
      cleaving enzyme 1 (BACE1) mediate the major activities of alpha-secretase and
      beta-secretase in brain and share various common substrates. However, whether
      they function separately or together is poorly understood. Here, we show that
      ADAM10 and BACE1 co-localize in the neurites of mouse primary neurons. Co
      immunoprecipitation and fluorescence resonance energy transfer analysis revealed
      that ADAM10 and BACE1 interact with each other under both endogenous and
      exogenous conditions. In addition, we found that ADAM10 enhances the proteolysis
      of neural cell adhesion molecule close homolog of L1 (CHL1) by BACE1. Further
      studies found that ADAM10-BACE1 interaction interfering peptide LT52 attenuates
      the regulation of ADAM10 on BACE1-mediated cleavage of CHL1. Our data indicate
      that ADAM10-BACE1 interaction regulates the proteolysis of some specific
      substrates and may play a potential role in brain function.

PMID- 29325092
TI  - Intravenous administration of scAAV9-Hexb normalizes lifespan and prevents
      pathology in Sandhoff disease mice.
AB  - Sandhoff disease (SD) is a rare inherited disorder caused by a deficiency of beta
      hexosaminidase activity which is fatal because no effective treatment is
      available. A mouse model of Hexb deficiency reproduces the key pathognomonic
      features of SD patients with severe ubiquitous lysosomal dysfunction, GM2
      accumulation, neuroinflammation and neurodegeneration, culminating in death at 4
      months. Here, we show that a single intravenous neonatal administration of a self
      complementary adeno-associated virus 9 vector (scAAV9) expressing the Hexb cDNA
      in SD mice is safe and sufficient to prevent disease development. Importantly, we
      demonstrate for the first time that this treatment results in a normal lifespan
      (over 700 days) and normalizes motor function assessed by a battery of behavioral
      tests, with scAAV9-treated SD mice being indistinguishable from wild-type
      littermates. Biochemical analyses in multiple tissues showed a significant
      increase in hexosaminidase A activity, which reached 10-15% of normal levels.
      AAV9 treatment was sufficient to prevent GM2 and GA2 storage almost completely in
      the cerebrum (less so in the cerebellum), as well as thalamic reactive gliosis
      and thalamocortical neuron loss in treated Hexb-/- mice. In summary, this study
      demonstrated a widespread protective effect throughout the entire CNS after a
      single intravenous administration of the scAAV9-Hexb vector to neonatal SD mice.

PMID- 29325094
TI  - Functional rescue of misfolding ABCA3 mutations by small molecular correctors.
AB  - Adenosine triphosphate (ATP)-binding cassette subfamily A member 3 (ABCA3), a
      phospholipid transporter in lung lamellar bodies (LBs), is essential for the
      assembly of pulmonary surfactant and LB biogenesis. Mutations in the ABCA3 gene
      are an important genetic cause for respiratory distress syndrome in neonates and
      interstitial lung disease in children and adults, for which there is currently no
      cure. The aim of this study was to prove that disease causing misfolding ABCA3
      mutations can be corrected in vitro and to investigate available options for
      correction. We stably expressed hemagglutinin (HA)-tagged wild-type ABCA3 or
      variants p.Q215K, p.M760R, p.A1046E, p.K1388N or p.G1421R in A549 cells and
      assessed correction by quantitation of ABCA3 processing products, their
      intracellular localization, resembling LB morphological integrity and analysis of
      functional transport activity. We showed that all mutant proteins except for
      M760R ABCA3 were rescued by the bithiazole correctors C13 and C17. These variants
      were also corrected by the chemical chaperone trimethylamine N-oxide and by low
      temperature. The identification of lead molecules C13 and C17 is an important
      step toward pharmacotherapy of ABCA3 misfolding-induced lung disease.

PMID- 29325095
TI  - Multiple gout tophi.

PMID- 29325093
TI  - A comprehensive Caenorhabditis elegans N-glycan shotgun array.
AB  - Here we present a Caenorhabditis elegans N-glycan shotgun array. This nematode
      serves as a model organism for many areas of biology including but not limited to
      tissue development, host-pathogen interactions, innate immunity, and genetics.
      Caenorhabditis elegans N-glycans contain structural motifs that are also found in
      other nematodes as well as trematodes and lepidopteran species. Glycan binding
      toxins that interact with C. elegans glycoconjugates also do so with some
      agriculturally relevant species, such as Haemonchus contortus, Ascaris suum,
      Oesophagostomum dentatum and Trichoplusia ni. This situation implies that protein
      carbohydrate interactions seen with C. elegans glycans may also occur in other
      species with related glycan structures. Therefore, this array may be useful to
      study these relationships in other nematodes as well as trematode and insect
      species. The array contains 134 distinct glycomers spanning a wide range of C.
      elegans N-glycans including the subclasses high mannose, pauci mannose, high
      fucose, mammalian-like complex and phosphorylcholine substituted forms. The
      glycans presented on the array have been characterized by two-dimensional
      separation, ion trap mass spectrometry, and lectin affinity. High fucose glycans
      were well represented and contain many novel core structures found in C. elegans
      as well as other species. This array should serve as an investigative platform
      for carbohydrate binding proteins that interact with N-glycans of C. elegans and
      over a range of organisms that contain glycan motifs conserved with this
      nematode.

PMID- 29325098
TI  - High Level of Neutrophil Extracellular Traps Correlates With Poor Prognosis of
      Severe Influenza A Infection.
AB  - Background: Most patients with severe infection with influenza A virus (IAV)
      progress to acute respiratory distress syndrome and even multiple organ
      dysfunction syndrome (MODS). Neutrophil extracellular traps (NETs) can be induced
      by pathogens and are responsible for immune tissue damage. We conducted a
      prospective study on the production and effects of NETs in H7N9 and H1N1
      patients. Methods: We investigated NET production in plasma and supernatant of
      cultured neutrophils by measuring cell-free deoxyribonucleic acid (DNA) and
      myeloperoxidase (MPO)-DNA complexes with PicoGreen dye and enzyme-linked
      immunosorbent assay methods, respectively. We also observed NET structure by
      immunofluorescence staining. Results: We found that patients with severe
      influenza showed elevated plasma NET level on the day of admission. Neutrophils
      from these patients showed higher capacity to release MPO-DNA complex in response
      to interleukin-8 or lipopolysaccharide stimulation. We also found that NETs from
      H7N9 and H1N1 patients increased the permeability of alveolar epithelial cells,
      and, consequently, NET production was positively correlated with acute physiology
      and chronic health evaluation (APACHE) II score and MODS. Conclusions: These data
      indicate that high level of NETs contributes to lung injury and is correlated
      with severity of disease. Thus, NETs might be a key factor to predict the poor
      prognosis in IAV patients.

PMID- 29325100
TI  - The path to becoming more efficacious: modern perspectives in the surgical
      treatment of atrial fibrillation.

PMID- 29325099
TI  - Quantitative survey on health and violence endured by refugees during their
      journey and in Calais, France.
AB  - Background: In 2015, more than 1 million refugees arrived in Europe. During their
      travels, refugees often face harsh conditions, violence and torture in transit
      countries, but there is a lack of quantitative evidence on their experiences. We
      present the results of a retrospective survey among refugees in the 'Jungle' of
      Calais, France, to document their health problems and the violence they endured
      during their journeys. Methods: We conducted a cross-sectional population-based
      survey in November and December 2015. The sample size was set at 402 individuals,
      and geospatial simple random sampling was used. We collected data on
      demographics, routes travelled, health status, violence and future plans.
      Results: Departures from the country of origin increased beginning in September
      2015. Sixty-one percent of respondents reported having at least one health
      problem, especially while in Calais. Overall, 65.6% (95% CI 60.3-70.6)
      experienced at least one violent event en route; 81.5% of refugees wanted to go
      to the UK. Conclusions: This first quantitative survey conducted among refugees
      in Europe provides important socio-demographic data on refugees living in Calais
      and describes the high rate of violence they encountered during their journeys.
      Similar documentation should be repeated throughout Europe in order to better
      respond to the needs of this vulnerable population.

PMID- 29325097
TI  - Barriers to health care services for migrants living with HIV in Spain.
AB  - Background: In Spain, migrants are disproportionately affected by HIV and
      experience high rates of late diagnosis. We investigated barriers to health care
      access among migrants living with HIV (MLWH) in Spain. Methods: Cross sectional
      electronic survey of 765 adult HIV-positive migrants recruited within 18 health
      care settings between July 2013 and July 2015. We collected epidemiological,
      demographic, behavioral and clinical data. We estimated the prevalence and risk
      factors of self-reported barriers to health care using multivariable logistic
      regression. Results: Of those surveyed, 672 (88%) had information on health care
      access barriers: 23% were women, 63% from Latin America and Caribbean, 14% from
      Sub-Saharan Africa and 15% had an irregular immigration status. Men were more
      likely to report barriers than women (24% vs. 14%, P = 0.009). The main barriers
      were: lengthy waiting times for an appointment (9%) or in the clinic (7%) and
      lack of a health card (7%). Having an irregular immigration status was a risk
      factor for experiencing barriers for both men (OR: (4.0 [95%CI: 2.2-7.2]) and
      women (OR: 10.5 [95%CI: 3.1-34.8]). Men who experienced racial stigma (OR: 3.1
      [95%CI: 1.9-5.1]) or food insecurity (OR: 2.1 [95%CI: 1.2-3.4]) were more likely
      to report barriers. Women who delayed treatment due to medication costs (6.3
      [95%CI: 1.3-30.8]) or had a university degree (OR: 5.8 [95%CI: 1.3-25.1]) were
      more likely to report barriers. Conclusion: Health care barriers were present in
      one in five5 MLWH, were more common in men and were associated to legal
      entitlement to access care, perceived stigma and financial constraints.

PMID- 29325096
TI  - Genetic Determinants of Circulating Estrogen Levels and Evidence of a Causal
      Effect of Estradiol on Bone Density in Men.
AB  - Context: Serum estradiol (E2) and estrone (E1) levels exhibit substantial
      heritability. Objective: To investigate the genetic regulation of serum E2 and E1
      in men. Design, Setting, and Participants: Genome-wide association study in
      11,097 men of European origin from nine epidemiological cohorts. Main Outcome
      Measures: Genetic determinants of serum E2 and E1 levels. Results: Variants
      in/near CYP19A1 demonstrated the strongest evidence for association with E2,
      resolving to three independent signals. Two additional independent signals were
      found on the X chromosome; FAMily with sequence similarity 9, member B (FAM9B),
      rs5934505 (P = 3.4 * 10-8) and Xq27.3, rs5951794 (P = 3.1 * 10-10). E1 signals
      were found in CYP19A1 (rs2899472, P = 5.5 * 10-23), in Tripartite motif
      containing 4 (TRIM4; rs17277546, P = 5.8 * 10-14), and CYP11B1/B2 (rs10093796, P
      = 1.2 * 10-8). E2 signals in CYP19A1 and FAM9B were associated with bone mineral
      density (BMD). Mendelian randomization analysis suggested a causal effect of
      serum E2 on BMD in men. A 1 pg/mL genetically increased E2 was associated with a
      0.048 standard deviation increase in lumbar spine BMD (P = 2.8 * 10-12). In men
      and women combined, CYP19A1 alleles associated with higher E2 levels were
      associated with lower degrees of insulin resistance. Conclusions: Our findings
      confirm that CYP19A1 is an important genetic regulator of E2 and E1 levels and
      strengthen the causal importance of E2 for bone health in men. We also report two
      independent loci on the X-chromosome for E2, and one locus each in TRIM4 and
      CYP11B1/B2, for E1.

PMID- 29325101
TI  - Fauna, Ecological Characteristics, and Checklist of the Mosquitoes in Mazandaran
      Province, Northern Iran.
AB  - Mosquitoes are important vectors of human and animal diseases. This study updates
      current knowledge on fauna, dominance, and distribution of mosquitoes in
      Mazandaran Province, Northern Iran, to inform disease control effort. Larval
      collections, using standard dippers or droppers, and adult collections, using
      total catches, shelter pits, CDC light traps, and human landing catches, were
      performed monthly in 30 villages across 16 counties, from May to December 2014.
      Ovitraps, baited with hay infusion as oviposition attractants or stimulants for
      Aedes (Stegomyia) mosquitoes, were installed in each village and inspected weekly
      for eggs. Lactophenol and Berlese media were used for preserving and mounting
      specimens. Overall, 36,024 mosquito specimens (19,840 larvae and 16,184 adults)
      belonging to 4 genera and 20 species were morphologically identified. The
      dominance and distribution indices showed that Culex pipiens s.s. was the
      eudominant species with a constant distribution of larvae (D = 69.07%, C = 100%)
      and adults (D = 31.86%, C = 100%), followed by Cx tritaeniorhynchus (D = 38.14%,
      C = 100%) and Anopheles maculipennis s.l. (D = 11.05%, C = 100%) as adults. Aedes
      vexans was the dominant (7.85%) species, but it had a sporadic (20%)
      distribution. Culex torrentium and Culiseta morsitans were added as the new
      species to the checklist of mosquitoes in Mazandaran Province. Due to the
      potential role, Cx. pipiens s.s. as a vector of various pathogens, further
      ecological studies are recommended.

PMID- 29325103
TI  - Twenty-year experience with stentless biological aortic valve and root
      replacement: informing patients of risks and benefits.
AB  - OBJECTIVES: The aim of this study was to provide predictive data on the
      performance of the Freestyle stentless bioprosthesis that can be used to support
      and improve the shared decision-making process of prosthetic valve choice for
      aortic valve replacement. METHODS: Between 1993 and 2014, 604 patients received
      the Freestyle stentless bioprosthesis (143 subcoronary, 58 root inclusion and 403
      full-root replacement). Perioperative data were collected retrospectively, and
      follow-up data were collected prospectively from 2015. Follow-up was 96% complete
      (median 4.3 years), with 114 (19%) patients having a follow-up period exceeding
      10 years. A competing risks regression model was developed to predict the
      probability of mortality, structural valve deterioration (SVD) and reoperation
      for other causes than SVD. RESULTS: The median age of patients was 64 years, 91
      (15%) patients had undergone previous aortic valve replacement and 351 (58%)
      underwent concomitant procedures. The 15-year probability of SVD, reoperation for
      other causes and death were 16.9%, 8.1% and 47.7%, respectively. Linearized
      occurrence rates for prosthesis endocarditis, thromboembolic events and bleeding
      were 0.5%, 0.9% and 0.1% per patient-year, respectively. The constructed
      predictive model, including age, renal function and implantation technique as
      significant covariates, had good to fair predictive performance up to 19 years.
      CONCLUSIONS: The Freestyle stentless bioprosthesis is an efficient prosthesis for
      aortic valve replacement or root replacement, with low incidences of SVD and
      valve-related events at long-term follow-up. The predictive model designed in
      this study can be used to fully inform patients about their expected individual
      trajectory after implantation of this prosthesis. This improves the shared
      decision-making process between patients and clinicians.

PMID- 29325102
TI  - Elevated Proportions of Deleterious Genetic Variation in Domestic Animals and
      Plants.
AB  - A fraction of genetic variants segregating in any population are deleterious,
      which negatively impacts individual fitness. The domestication of animals and
      plants is associated with population bottlenecks and artificial selection, which
      are predicted to increase the proportion of deleterious variants. However, the
      extent to which this is a general feature of domestic species is unclear. Here,
      we examine the effects of domestication on the prevalence of deleterious
      variation using pooled whole-genome resequencing data from five domestic animal
      species (dog, pig, rabbit, chicken, and silkworm) and two domestic plant species
      (rice and soybean) compared with their wild ancestors. We find significantly
      reduced genetic variation and increased proportion of nonsynonymous amino acid
      changes in all but one of the domestic species. These differences are observable
      across a range of allele frequencies, both common and rare. We find
      proportionally more single nucleotide polymorphisms in highly conserved elements
      in domestic species and a tendency for domestic species to harbor a higher
      proportion of changes classified as damaging. Our findings most likely reflect an
      increased incidence of deleterious variants in domestic species, which is most
      likely attributable to population bottlenecks that lead to a reduction in the
      efficacy of selection. An exception to this pattern is displayed by European
      domestic pigs, which do not show traces of a strong population bottleneck and
      probably continued to exchange genes with wild boar populations after
      domestication. The results presented here indicate that an elevated proportion of
      deleterious variants is a common, but not ubiquitous, feature of domestic
      species.

PMID- 29325105
TI  - Predictors of Secondary Role Strains Among Spousal Caregivers of Older Adults
      With Functional Disability.
AB  - Background and Objectives: Aging spouses commonly care for a partner with
      functional disability, but little is known about how spousal caregiving may
      impact different life domains. This study evaluated how caregiving
      characteristics are associated with secondary role strains among spousal
      caregivers. Research Design and Methods: This cross-sectional study examined 367
      spousal caregivers and their partners from the 2011 National Health and Aging
      Trends Study and National Study of Caregiving. Hierarchical regressions were
      estimated to determine how caregiver background factors (sociodemographics,
      health conditions) along with primary objective (care activities, care recipient
      health conditions, and dementia status) and subjective (emotional caregiving
      difficulties, role overload) stressors are linked to care-related valued activity
      restriction, negative caregiving relationship quality, and care-related family
      disagreements. Gender differences were considered. Results: After accounting for
      all predictors, older caregivers and caregivers providing more help with
      activities of daily living and health system interactions (e.g., scheduling
      appointments) were more likely to report activity restriction, whereas caregivers
      with more emotional difficulties reported higher negative caregiving relationship
      quality. Role overload was positively associated with all three secondary
      strains. For husbands only, caring for a partner with more chronic conditions was
      linked to higher negative caregiving relationship quality and caring for a
      partner with dementia was associated with a greater likelihood of family
      disagreements. Discussion and Implications: Secondary role strains may develop
      through similar and unique pathways for caregiving wives and husbands. Further
      research is needed to identify those who could benefit from support in managing
      their care responsibilities alongside other life areas.

PMID- 29325104
TI  - Eukaryotic translational termination efficiency is influenced by the 3'
      nucleotides within the ribosomal mRNA channel.
AB  - When a stop codon is at the 80S ribosomal A site, there are six nucleotides (+4
      to +9) downstream that are inferred to be occupying the mRNA channel. We examined
      the influence of these downstream nucleotides on translation termination success
      or failure in mammalian cells at the three stop codons. The expected hierarchy in
      the intrinsic fidelity of the stop codons (UAA>UAG>>UGA) was observed, with
      highly influential effects on termination readthrough mediated by nucleotides at
      position +4 and position +8. A more complex influence was observed from the
      nucleotides at positions +5 and +6. The weakest termination contexts were most
      affected by increases or decreases in the concentration of the decoding release
      factor (eRF1), indicating that eRF1 binding to these signals was rate-limiting.
      When termination efficiency was significantly reduced by cognate suppressor
      tRNAs, the observed influence of downstream nucleotides was maintained. There was
      a positive correlation between experimentally measured signal strength and
      frequency of the signal in eukaryotic genomes, particularly in Saccharomyces
      cerevisiae and Drosophila melanogaster. We propose that termination efficiency is
      not only influenced by interrogation of the stop signal directly by the release
      factor, but also by downstream ribosomal interactions with the mRNA nucleotides
      in the entry channel.

PMID- 29325106
TI  - Transcriptomic profiling of interacting nasal staphylococci species reveals
      global changes in gene and non-coding RNA expression.
AB  - Interspecies interactions between bacterial pathogens and the commensal
      microbiota can influence disease outcome. In the nasal cavities, Staphylococcus
      epidermidis has been shown to be a determining factor for Staphylococcus aureus
      colonization and biofilm formation. However, the interaction between S.
      epidermidis and S. aureus has mainly been described by phenotypic analysis, and
      little is known about how this interaction modulates gene expression. This study
      aimed to determine the interactome of nasal S. aureus and S. epidermidis isolates
      to understand the molecular effect of interaction. After whole-genome sequencing
      of two nasal staphylococcal isolates, an agar-based RNA sequencing setup was
      utilized to identify interaction-induced transcriptional alterations in surface
      associated populations. Our results revealed differential expression of several
      virulence genes in both species. We also identified putative non-coding RNAs
      (ncRNAs) and, interestingly, detected a putative ncRNA transcribed antisense to
      esp, the serine protease of S. epidermidis, that has previously been shown to
      inhibit nasal colonization of S. aureus. In our study, the gene encoding Esp and
      the antisense ncRNA are both downregulated during interaction with S. aureus. Our
      findings contribute to a better understanding of pathogen physiology in the
      context of interactions with the commensal microbiota, and may provide targets
      for future therapeutics.

PMID- 29325107
TI  - 2'-O-(2-Methoxyethyl) Nucleosides Are Not Phosphorylated or Incorporated Into the
      Genome of Human Lymphoblastoid TK6 Cells.
AB  - Nucleoside analogs with 2'-modified sugar moieties are often used to improve the
      RNA target affinity and nuclease resistance of therapeutic oligonucleotides in
      preclinical and clinical development. Despite their enhanced nuclease resistance,
      oligonucleotides could slowly degrade releasing nucleoside analogs that have the
      potential to become phosphorylated and incorporated into cellular DNA and RNA.
      For the first time, the phosphorylation and DNA/RNA incorporation of 2'-O-(2
      methoxyethyl) (2'-O-MOE) nucleoside analogs have been investigated. Using liquid
      chromatography/tandem mass spectrometry, we showed that enzymes in the nucleotide
      salvage pathway including deoxycytidine kinase (dCK) and thymidine kinase (TK1)
      displayed poor reactivity toward 2'-O-MOE nucleoside analogs. On the other hand,
      2'-fluoro (F) nucleosides, regardless of the nucleobase, were efficiently
      phosphorylated to their monophosphate forms by dCK and TK1. Consistent with their
      efficient phosphorylation by dCK and TK1, 2'-F nucleoside analogs were
      incorporated into cellular DNA and RNA while no incorporation was detected with
      2'-O-MOE nucleoside analogs. In conclusion, these data suggest that the inability
      of dCK and TK1 to create the monophosphates of 2'-O-MOE nucleoside analogs
      reduces the risk of their incorporation into cellular DNA and RNA.

PMID- 29325109
TI  - Estimating adolescent sleep need using dose-response modeling.
AB  - Study Objectives: This study will (1) estimate the nightly sleep need of human
      adolescents, (2) determine the time course and severity of sleep-related deficits
      when sleep is reduced below this optimal quantity, and (3) determine whether
      sleep restriction perturbs the circadian system as well as the sleep homeostat.
      Methods: Thirty-four adolescents aged 15 to 17 years spent 10 days and nine
      nights in the sleep laboratory. Between two baseline nights and two recovery
      nights with 10 hours' time in bed (TIB) per night, participants experienced
      either severe sleep restriction (5-hour TIB), moderate sleep restriction (7.5
      hour TIB), or no sleep restriction (10-hour TIB) for five nights. A 10-minute
      psychomotor vigilance task (PVT; lapse = response after 500 ms) and the
      Karolinska Sleepiness Scale were administered every 3 hours during wake. Salivary
      dim-light melatonin onset was calculated at baseline and after four nights of
      each sleep dose to estimate circadian phase. Results: Dose-dependent deficits to
      sleep duration, circadian phase timing, lapses of attention, and subjective
      sleepiness occurred. Less TIB resulted in less sleep, more lapses of attention,
      greater subjective sleepiness, and larger circadian phase delays. Sleep need
      estimated from 10-hour TIB sleep opportunities was approximately 9 hours, while
      modeling PVT lapse data suggested that 9.35 hours of sleep is needed to maintain
      optimal sustained attention performance. Conclusions: Sleep restriction perturbs
      homeostatic and circadian systems, leading to dose-dependent deficits to
      sustained attention and sleepiness. Adolescents require more sleep for optimal
      functioning than typically obtained.

PMID- 29325108
TI  - Aging is associated with a prefrontal lateral-medial shift during picture-induced
      negative affect.
AB  - The capacity to adaptively respond to negative emotion is in part dependent upon
      lateral areas of the prefrontal cortex (PFC). Lateral PFC areas are particularly
      susceptible to age-related atrophy, which affects executive function (EF). We
      used structural and functional magnetic resonance imaging (MRI) to test the
      hypothesis that older age is associated with greater medial PFC engagement during
      processing of negative information, and that this engagement is dependent upon
      the integrity of grey matter structure in lateral PFC as well as EF. Participants
      (n = 64, 38-79 years) viewed negative and neutral scenes while in the scanner,
      and completed cognitive tests as part of a larger study. Grey matter probability
      (GMP) was computed to index grey matter integrity. FMRI data demonstrated less
      activity in the left ventrolateral PFC (VLPFC) and greater ventromedial PFC
      (VMPFC) activity with increasing age during negative-picture viewing. Age did not
      correlate with amygdala responding. GMP in VLPFC and EF were negatively
      associated with VMPFC activity. We conclude that this change from lateral to
      medial PFC engagement in response to picture-induced negative affect reflects
      decreased reliance on executive function-related processes, possibly associated
      with reduced grey matter in lateral PFC, with advancing age to maintain emotional
      functioning.

PMID- 29325110
TI  - Impact of genetic risk loci for multiple sclerosis on expression of proximal
      genes in patients.
AB  - Despite advancements in genetic studies, it is difficult to understand and
      characterize the functional relevance of disease-associated genetic variants,
      especially in the context of a complex multifactorial disease such as multiple
      sclerosis (MS). As a large proportion of expression quantitative trait loci
      (eQTLs) are context-specific, we performed RNA-Seq in peripheral blood
      mononuclear cells from MS patients (n = 145) to identify eQTLs in regions
      centered on 109 MS risk single nucleotide polymorphisms and 7 associated human
      leukocyte antigen variants. We identified 77 statistically significant eQTL
      associations, including pseudogenes and non-coding RNAs. Thirty-eight out of 40
      testable eQTL effects were colocalized with the disease association signal. As
      many eQTLs are tissue specific, we aimed to detail their significance in
      different cell types. Approximately 70% of the eQTLs were replicated and
      characterized in at least one major peripheral blood mononuclear cell-derived
      cell type. Furthermore, 40% of eQTLs were found to be more pronounced in MS
      patients compared with non-inflammatory neurological diseases patients. In
      addition, we found two single nucleotide polymorphisms to be significantly
      associated with the proportions of three different cell types. Mapping to
      enhancer histone marks and predicted transcription factor binding sites added
      additional functional evidence for eight eQTL regions. As an example, we found
      that rs71624119, shared with three other autoimmune diseases and located in a
      primed enhancer (H3K4me1) with potential binding for STAT transcription factors,
      significantly associates with ANKRD55 expression. This study provides many novel
      and validated targets for future functional characterization of MS and other
      diseases.

PMID- 29325111
TI  - Risk of coronary heart disease among smokeless tobacco users: results of
      systematic review and meta-analysis of global data.
AB  - Background: Use of smokeless tobacco (SLT) products has been linked to multiple
      adverse effects, especially precancer and cancer of oral cavity. However, the
      association of SLT use with risk of coronary heart disease (CHD) is shrouded with
      controversy due to conflicting results in the literature. The present meta
      analysis aimed to evaluate the risk of CHD among adult ever-users of SLT products
      along with subgroup analysis. Methods: The analysis included studies retrieved
      from a systematic literature search for published articles assessing risk of CHD
      with SLT use. Two authors independently extracted risk estimates and study
      characteristics of the included studies. Summary relative risks were estimated
      using the random-effect model. Results: Twenty studies from four WHO regions were
      included in the analysis. The summary risk of CHD in SLT users was not
      significantly positive (1.05, 95% CI 0.96-1.15) although a higher risk of fatal
      CHD was seen (1.10, 95% CI 1.00-1.20). The risk was significant for users in
      European Region (1.30, 95% CI 1.14-1.47). The results remained unchanged even
      after strict adjustment for smoking. Product-wise analysis revealed a significant
      positive association of fatal CHD with snus/ snuff use (1.37, 95% CI 1.14-1.61).
      The SLT-attributable fraction of fatal CHD was calculated to be 0.3%, highest
      being for European region (5%). Conclusion: A significant positive association
      was detected between SLT use and risk of fatal CHD, especially for European users
      and those consuming snus/ snuff. In view of the positive association even after
      strict adjustment for smoking, these results underscore the need for inclusion of
      cessation efforts for smokeless tobacco in addition to smoking for control of
      fatal cardiovascular diseases. Implications: The present meta-analysis
      demonstrates a global perspective of association between coronary heart disease
      (CHD) and use of smokeless tobacco (SLT), especially for fatal cardiac events,
      even with strict adjustment for smoking. There appears to be some difference in
      this effect based on the type of SLT product used. These results highlight the
      independent deleterious effect of SLT products on the outcome of CHD and might
      help to resolve the long-standing controversy regarding the association of SLT
      with the risk of CHD. Hence, we propose that in addition to smoking, cessation
      efforts should be directed towards SLT products as well, for control of
      cardiovascular diseases.

PMID- 29325112
TI  - Autologous Haematopoietic Stem Cell Transplantation (AHSCT) in Severe Crohn's
      Disease: A Review on Behalf of ECCO and EBMT.
AB  - Despite the major recent progress in the treatment of Crohn's disease [CD], there
      is a subset of patients in whom the disease runs an aggressive course with
      progressive tissue damage requiring early and repeated surgical management.
      Increasing evidence supports sustained and profound improvement in
      gastrointestinal parameters and quality of life following high-dose
      immunosuppressive therapy and autologous haematopoietic stem cell transplantation
      [AHSCT] compared to standard therapy in this context. In addition, international
      transplant registry data reflect the use of AHSCT in CD outside of trials in
      selected patients. However, AHSCT may be associated with significant treatment
      related complications with risk of transplant-related mortality. In a joint
      initiative, the European Crohn's and Colitis Organisation [ECCO] and the European
      Society for Blood and Marrow Transplantation [EBMT] have produced a state-of-the
      art review of the rationale, evaluation, patient selection, stem cell
      mobilization and transplant procedures and long-term follow up. Given the unique
      spectrum of issues, we recommend that AHSCT should only be performed in
      experienced centres with expertise in both haematological and gastroenterological
      aspects of the procedure. Where possible, patients should be enrolled on clinical
      trials and data registered centrally. Future development should be coordinated at
      both national and international levels.

PMID- 29325113
TI  - Vitality club: a proof-of-principle of peer coaching for daily physical activity
      by older adults.
AB  - Many age-related diseases can be prevented or delayed by daily physical activity.
      Unfortunately, many older adults do not perform physical activity at the
      recommended level. Professional interventions do not reach large numbers of older
      adults for a long period of time. We studied a peer-coach intervention, in which
      older adults coach each other, that increased daily physical activity of
      community dwelling older adults for over 6 years. We studied the format and
      effects of this peer coach intervention for possible future implementation
      elsewhere. Through interviews and participatory observation we studied the format
      of the intervention. We also used a questionnaire (n = 55) and collected 6-min
      walk test data (n = 261) from 2014 to 2016 to determine the motivations of
      participants and effects of the intervention on health, well-being and physical
      capacity. Vitality Club is a self-sustainable group of older adults that gather
      every weekday to exercise coached by an older adult. Members attend on average
      2.5 days per week and retention rate is 77.5% after 6 years. The members
      perceived improvements in several health measures. In line with this, the 6-min
      walk test results of members of this Vitality Club improved with 21.7 meters per
      year, compared with the decline of 2-7 meters per year in the general population.
      This Vitality Club is successful in durably engaging its members in physical
      activity. The members perceive improvements in health that are in line with
      improvements in a physical function test. Because of the self-sustainable
      character of the intervention, peer coaching has the potential to be scaled up at
      low cost and increase physical activity in the increasing number of older adults.

PMID- 29325114
TI  - Distribution of pines in the Iberian Peninsula agrees with species differences in
      foliage frost tolerance, not with vulnerability to freezing-induced xylem
      embolism.
AB  - Drought and frosts are major determinants of plant functioning and distribution.
      Both stresses can cause xylem embolism and foliage damage. The objective of this
      study was to analyse if the distribution of six common pine species along
      latitudinal and altitudinal gradients in Europe is related to their interspecific
      differences in frost tolerance and to the physiological mechanisms underlying
      species-specific frost tolerance. We also evaluate if frost tolerance depends on
      plant water status. We studied survival to a range of freezing temperatures in 2
      year-old plants and assessed the percentage loss of hydraulic conductivity (PLC)
      due xylem embolism formation and foliage damage determined by needle electrolyte
      leakage (EL) after a single frost cycle to -15  degrees C and over a range of
      predawn water potential (psipd) values. Species experiencing cold winters in
      their range (Pinus nigra J.F. Arnold, Pinus sylvestris L. and Pinus uncinata
      Raymond ex A. DC.) had the highest frost survival rates and lowest needle EL and
      soluble sugar (SS) concentration. In contrast, the pines inhabiting mild or cool
      winter locations (especially Pinus halepensis Mill. and Pinus pinea L. and, to a
      lesser extent, Pinus pinaster Ait.) had the lowest frost survival and highest
      needle EL and SS values. Freezing-induced PLC was very low and differences among
      species were not related to frost damage. Reduction in psipd decreased leaf frost
      damage in P. pinea and P. sylvestris, increased it in P. uncinata and had a
      neutral effect on the rest of the species. This study demonstrates that freezing
      temperatures are a major environmental driver for pine distribution and suggests
      that interspecific differences in leaf frost sensitivity rather than
      vulnerability to freezing-induced embolism or SS explain pine juvenile frost
      survival.

PMID- 29325115
TI  - Fast sleep spindle density is associated with rs4680 (Val108/158Met) genotype of
      catechol-O-methyltransferase (COMT).
AB  - Study Objectives: Sleep spindles are a hallmark of NREM stage 2 sleep. Fast sleep
      spindles correlate with cognitive functioning and are reduced in schizophrenia.
      Although spindles are highly genetically determined, distinct genetic mechanisms
      influencing sleep spindle activity have not been identified so far. Spindles are
      generated within a thalamocortical network. Dopaminergic neurotransmission
      modulates activity within this network and importantly depends on activity of
      catechol-O-methyltransferase (COMT). We aimed at testing whether the common
      functional rs4680 (Val108/158Met) polymorphism of COMT modulates fast spindle
      activity in healthy participants. Methods: In 150 healthy participants (93 women,
      57 men; mean age 30.9 +/- 11.6 years) sleep spindle density was analyzed during
      the second of two nights of polysomnography. We investigated the effect of the
      COMT Val108/158Met genotype on fast spindle density in whole-night NREM sleep
      stages N2 and N3. Results: As predicted, higher Val allele dose correlates with
      reduced fast spindle density. Additional exploratory analysis of the effect of
      COMT genotype revealed that slow spindle density in heterozygote participants was
      lower than that of both homozygote groups. Morphological characteristics of fast
      and slow spindles did not show significant differences between genotypes. COMT
      genotype had also no significant effect on measures of general sleep quality.
      Conclusions: This is the first report of a distinct gene effect on sleep spindle
      density in humans. As variation in the COMT Val108/158Met polymorphism is
      associated with differential expression of fast spindles in healthy participants,
      genetically determined dopaminergic neurotransmission may modulate spindle
      oscillations during NREM sleep. Clinical Trial registration: DRKS00008902.

PMID- 29325116
TI  - Differential expression of antimicrobial peptides in corneal infection and
      regulation of antimicrobial peptides and reactive oxygen species by type III
      secretion system of Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa is an opportunistic pathogen and is the major cause of
      corneal infection worldwide that secret several virulent toxins through its type
      III secretion system (T3SS). In defense against pathogenic insults, epithelial
      cells and macrophages express antimicrobial peptides (AMPs) that are essential
      components of host immune response. In this study, we have determined the
      expression of several AMPs in patients with P. aeruginosa corneal infection. We
      also used an in vitro model of infection using human corneal epithelial cells and
      macrophages to determine the gene expression of AMPs and cellular response to
      wild-type and T3SS mutant P. aeruginosa. We found differential expression of
      several AMPs in patient samples and also found that P. aeruginosa repress AMP
      expression in both epithelial cells and macrophages by its T3SS in vitro. It
      dampens AMP expression by causing delay in NF-kappaB, p38 and ERK activation and
      inhibits reactive oxygen species generation in these cells by its T3SS. Our study
      show the profile of AMPs expressed during P. aeruginosa keratitis and suggest the
      pivotal role of the T3SS in epithelial cells and macrophages during P. aeruginosa
      infection.

PMID- 29325117
TI  - Prospective Discrimination of Controllers From Progressors Early After Low-Dose
      Mycobacterium tuberculosis Infection of Cynomolgus Macaques using Blood RNA
      Signatures.
AB  - The cynomolgus macaque model of low-dose Mycobacterium tuberculosis infection
      recapitulates clinical aspects of human tuberculosis pathology, but it is unknown
      whether the 2 systems are sufficiently similar that host-based signatures of
      tuberculosis will be predictive across species. By blind prediction, we
      demonstrate that a subset of genes comprising a human signature for tuberculosis
      risk is simultaneously predictive in humans and macaques and prospectively
      discriminates progressor from controller animals 3-6 weeks after infection.
      Further analysis yielded a 3-gene signature involving PRDX2 that predicts
      tuberculosis progression in macaques 10 days after challenge, suggesting novel
      pathways that define protective responses to M. tuberculosis.

PMID- 29325118
TI  - Interactive effects of phosphorus, calcium, and phytase supplements on products
      of phytate degradation in the digestive tract of broiler chickens.
AB  - This study aimed to distinguish between the single and interactive effects of
      phosphorus (P), calcium (Ca), and phytase on products of phytate degradation,
      including the disappearance of myo-inositol (MI), P, Ca, and amino acids (AA) in
      different segments of the digestive tract in broiler chickens. Additionally, all
      dephosphorylation steps from myo-inositol 1,2,3,4,5,6-hexakis (dihydrogen
      phosphate) (InsP6) to MI were investigated in the digesta of the terminal ileum.
      Unsexed Ross 308 broiler chickens were allocated to 56 pens with 19 birds per
      pen, and assigned to one of 8 dietary treatments. The dietary treatments included
      diets without (P-, 4.1 g/kg DM) or with (P+, 6.9 g/kg DM) monosodium phosphate
      supplementation, without (Ca-, 6.2 g/kg DM) or with (Ca+, 10.3 g/kg DM)
      additional fine limestone supplementation, and without or with 1,500 FTU
      phytase/kg feed in a factorial design. Adding Ca or P had no effect on InsP6
      disappearance in the crop when phytase was added. InsP6 disappearance up to the
      terminal ileum (P-Ca- 56%) was decreased in P+Ca- (40%), and even more so in
      P+Ca+ (21%), when no phytase was added. Adding phytase removed all effects of P
      and Ca (77 to 87%); however, P+Ca+ increased the concentrations of lower InsP
      esters and reduced free MI in the ileum, even in the presence of phytase. These
      results indicate that mineral supplements, especially P and Ca combined, reduce
      the efficacy of endogenous microbial or epithelial phosphatases. Supplementation
      with phytase increased, while supplementation with Ca decreased the concentration
      of MI in all segments of the digestive tract and in blood plasma, demonstrating
      the ability of broilers to fully degrade phytate and absorb released MI. While AA
      disappearance was not affected by P or Ca, or an interaction among P, Ca, and
      phytase, it increased with the addition of phytase by 2 to 6%. This demonstrates
      the potential of the phytase used to increase AA digestibility, likely
      independent of P and Ca supply.

PMID- 29325119
TI  - miR-96 is required for normal development of the auditory hindbrain.
AB  - The peripheral deafness gene Mir96 is expressed in both the cochlea and central
      auditory circuits. To investigate whether it plays a role in the auditory system
      beyond the cochlea, we characterized homozygous Dmdo/Dmdo mice with a point
      mutation in miR-96. Anatomical analysis demonstrated a significant decrease in
      volume of auditory nuclei in Dmdo/Dmdo mice. This decrease resulted from
      decreased cell size. Non-auditory structures in the brainstem of Dmdo/Dmdo mice
      or auditory nuclei of the congenital deaf Cldn14-/- mice revealed no such
      differences. Electrophysiological analysis in the medial nucleus of the trapezoid
      body (MNTB) showed that principal neurons fired preferentially multiple action
      potentials upon depolarization, in contrast to the single firing pattern
      prevalent in controls and Cldn14-/- mice. Immunohistochemistry identified
      significantly reduced expression of two predicted targets of the mutated miR-96,
      Kv1.6 and BK channel proteins, possibly contributing to the electrophysiological
      phenotype. Microscopic analysis of the Dmdo/Dmdo calyx of Held revealed a largely
      absent compartmentalized morphology, as judged by SV2-labeling. Furthermore, MNTB
      neurons from Dmdo/Dmdo mice displayed larger synaptic short-term depression,
      slower AMPA-receptor decay kinetics and a larger NMDA-receptor component,
      reflecting a less matured stage. Again, these synaptic differences were not
      present between controls and Cldn14-/- mice. Thus, deafness genes differentially
      affect the auditory brainstem. Furthermore, our study identifies miR-96 as an
      essential gene regulatory network element of the auditory system which is
      required for functional maturation in the peripheral and central auditory system
      alike.

PMID- 29325120
TI  - Strigolactone Biosynthesis Genes of Rice are Required for the Punctual Entry of
      Arbuscular Mycorrhizal Fungi into the Roots.
AB  - Arbuscular mycorrhiza (AM) is a mutualistic association between most plant
      species and the ancient fungal phylum Glomeromycota in roots, and it plays a key
      role in a plant's nutrient uptake from the soil. Roots synthesize strigolactones
      (SLs), derivatives of carotenoids, and exude them to induce energy metabolism and
      hyphal branching of AM fungi. Despite the well-documented roles of SLs in the pre
      symbiotic phase, little is known about the role of SLs in the process of root
      colonization. Here we show that the expansion of root colonization is suppressed
      in the mutants of rice (Oryza sativa) SL biosynthesis genes, carotenoid cleavage
      dioxygenase D10 and more severely in D17. Interestingly, most of the colonization
      process is normal, i.e. AM fungal hyphae approach the roots and cling around
      them, and epidermal penetration, arbuscule size, arbuscule number per hyphopodium
      and metabolic activity of the intraradical mycelium are not affected in d10 and
      d17 mutants. In contrast, hyphopodium formation is severely attenuated. Our
      observations establish the requirement for SL biosynthesis genes for efficient
      hyphopodium formation, suggesting that SLs are required in this process.
      Efficient hyphopodium formation is required for the punctual internalization of
      hyphae into roots and maintaining the expansion of colonization.

PMID- 29325121
TI  - Plasma 25-Hydroxyvitamin D and Mortality in Patients With Suspected Stable Angina
      Pectoris.
AB  - Context and Objective: Vitamin D status may affect cardiovascular disease (CVD)
      development and survival. We studied the relationship between concentrations of
      the circulating biomarker 25-hydroxyvitamin D (25OHD) and all-cause and
      cardiovascular mortality risk. Design, Setting, Participants, and Main Outcome
      Measures: 25OHD, the sum of 25-hydroxyvitamin D3 and 25-hydroxyvitamin D2, was
      analyzed in plasma samples from 4114 white patients suspected of having stable
      angina pectoris and was adjusted for seasonal variation. Hazard ratios (HRs) for
      all-cause and cardiovascular mortality were estimated by using multivariable Cox
      models with 25OHD as the main exposure variable, with adjustment for study site,
      age, sex, smoking, body mass index, estimated glomerular filtration rate, and
      systolic blood pressure. Results: A total of 895 (21.8%) deaths, including 407
      (9.9%) from CVD causes, occurred during a mean +/- standard deviation follow-up
      of 11.9 +/- 3.0 years. Compared with the first 25OHD quartile, HRs in the second,
      third, and fourth quartiles were 0.64 [95% confidence interval (CI), 0.54 to
      0.77], 0.56 (95% CI, 0.46 to 0.67), and 0.56 (95% CI, 0.46 to 0.67) for all-cause
      mortality and 0.70 (95% CI, 0.53 to 0.91), 0.60 (95% CI, 0.45 to 0.79), and 0.57
      (95% CI, 0.43 to 0.75) for cardiovascular mortality, respectively. Threshold
      analysis demonstrated increased all-cause and CVD mortality in patients with
      25OHD concentrations below ~42.5 nmol/L. Moreover, analysis suggested increased
      all-cause mortality at concentrations >100 nmol/L. Conclusion: Plasma 25OHD
      concentrations were inversely associated with cardiovascular mortality and
      nonlinearly (U-shaped) associated with all-cause mortality.

PMID- 29325122
TI  - LINEs Contribute to the Origins of Middle Bodies of SINEs besides 3' Tails.
AB  - Short interspersed elements (SINEs), which are nonautonomous transposable
      elements, require the transposition machinery of long interspersed elements
      (LINEs) to mobilize. SINEs are composed of two or more independently originating
      parts. The 5' region is called the "head" and is derived mainly from small RNAs,
      and the 3' region ("tail") originates from the 3' region of LINEs and is
      responsible for being recognized by counterpart LINE proteins. The origin of the
      middle "body" of SINEs is enigmatic, although significant sequence similarities
      among SINEs from very diverse species have been observed. Here, a systematic
      analysis of the similarities among SINEs and LINEs deposited on Repbase, a
      comprehensive database of eukaryotic repeat sequences was performed. Three
      primary findings are described: 1) The 5' regions of only two clades of LINEs,
      RTE and Vingi, were revealed to have contributed to the middle parts of SINEs; 2)
      The linkage of the 5' and 3' parts of LINEs can be lost due to occasional tail
      exchange of SINEs; and 3) The previously proposed Ceph-domain was revealed to be
      a fusion of a CORE-domain and a 5' part of RTE clade of LINE. Based on these
      findings, a hypothesis that the 5' parts of bipartite nonautonomous LINEs, which
      possess only the 5' and 3' regions of the original LINEs, can contribute to the
      undefined middle part of SINEs is proposed.

PMID- 29325124
TI  - Limited salt consumption reduces the incidence of chronic kidney disease: a
      modeling study.
AB  - Background: In addition to blood pressure and cardiovascular disease, high-salt
      intake has been associated with renal diseases. The aim of this study is to
      estimate the potential health impact of salt reduction on chronic kidney disease
      (CKD) and end-stage kidney disease (ESKD) in the Netherlands. Methods: We
      developed a dynamic population health modeling tool to estimate the health impact
      of salt reduction on CKD and ESKD. We used data from the PREVEND study and
      extrapolated that to the Dutch population aged 30-75 years. We estimated the
      potential health impact of salt reduction comparing the current situation with
      the health impact of the adherence to the recommended maximum salt intake of 6
      g/d. Results: In the recommended maximum intake scenario, a cumulative reduction
      in CKD of 1.1% (N = 290 000; interquartile range (IQR) = 249 000) and in ESKD of
      3.2% (N = 470; IQR = 5080) would occur over a period of 20 years. Conclusions:
      Our health impact estimation showed that health benefits on CKD might be achieved
      when salt intake is reduced to the recommended maximum intake of 6 g/d.

PMID- 29325123
TI  - Packaging of Dinoroseobacter shibae DNA into Gene Transfer Agent Particles Is Not
      Random.
AB  - Gene transfer agents (GTAs) are phage-like particles which contain a fragment of
      genomic DNA of the bacterial or archaeal producer and deliver this to a recipient
      cell. GTA gene clusters are present in the genomes of almost all marine
      Rhodobacteraceae (Roseobacters) and might be important contributors to horizontal
      gene transfer in the world's oceans. For all organisms studied so far, no obvious
      evidence of sequence specificity or other nonrandom process responsible for
      packaging genomic DNA into GTAs has been found. Here, we show that knock-out of
      an autoinducer synthase gene of Dinoroseobacter shibae resulted in overproduction
      and release of functional GTA particles (DsGTA). Next-generation sequencing of
      the 4.2-kb DNA fragments isolated from DsGTAs revealed that packaging was not
      random. DNA from low-GC conjugative plasmids but not from high-GC chromids was
      excluded from packaging. Seven chromosomal regions were strongly overrepresented
      in DNA isolated from DsGTA. These packaging peaks lacked identifiable conserved
      sequence motifs that might represent recognition sites for the GTA terminase
      complex. Low-GC regions of the chromosome, including the origin and terminus of
      replication, were underrepresented in DNA isolated from DsGTAs. DNA methylation
      reduced packaging frequency while the level of gene expression had no influence.
      Chromosomal regions found to be over- and underrepresented in DsGTA-DNA were
      regularly spaced. We propose that a "headful" type of packaging is initiated at
      the sites of coverage peaks and, after linearization of the chromosomal DNA,
      proceeds in both directions from the initiation site. GC-content, DNA
      modifications, and chromatin structure might influence at which sides GTA
      packaging can be initiated.

PMID- 29325125
TI  - Age, phosphorus, and 25-hydroxycholecalciferol regulate mRNA expression of
      vitamin D receptor and sodium-phosphate cotransporter in the small intestine of
      broiler chickens.
AB  - Four experiments were conducted in this study. Experiment 1 was carried out to
      examine mRNA expressions of nuclear vitamin D receptor (nVDR), membrane vitamin D
      receptor (mVDR), and type IIb sodium-phosphate cotransporter (NaPi-IIb) in the
      small intestine of broiler chickens. Experiments 2, 3, and 4 were implemented to
      evaluate effects of age, non-phytate phosphorus (NPP), and 25
      hydroxycholecalciferol (25-OH-D3) on mRNA expressions of nVDR, mVDR, and NaPi-IIb
      in the duodenum of chickens. Results showed that mRNA expression levels of nVDR
      and NaPi-IIb were highest in the duodenum of 21-day-old broilers, lower in the
      jejunum, and lowest in the ileum. By contrast, no differences in mRNA expression
      levels of mVDR were detected among the duodenum, jejunum, and ileum. Age
      quadratically affected mRNA expressions of nVDR, mVDR, and NaPi-IIb in the
      duodenum and 25-hydroxylase in the liver of 7- to 42-day-old broilers, with the
      highest levels observed at 21 d of age. By contrast, age linearly decreased mRNA
      expression level of 1alpha-hydroxylase in kidneys. Dietary NPP levels
      quadratically affected mRNA expression levels of nVDR and mVDR in the duodenum
      and 25-hydroxylase in the liver of 21-day-old broilers. The highest mRNA
      expression levels of nVDR and mVDR and lowest mRNA level of 25-hydroxylase were
      observed at 0.55% NPP. mRNA expression level of NaPi-IIb linearly declined when
      dietary NPP levels increased from 0.25 to 0.65%. Addition of 12.5 MUg/kg of 25-OH
      D3 increased mRNA expression level of 1alpha-hydroxylase in kidneys and those of
      nVDR, mVDR, and NaPi-IIb in the duodenum of broilers compared with birds fed the
      diet without 25-OH-D3. These data indicate that mRNA expressions of nVDR and NaPi
      IIb are highest in the duodenum, and the greatest mRNA levels of nVDR, mVDR, and
      NaPi-IIb are observed at 21 d of age. Dietary NPP levels quadratically increase
      mRNA expressions of nVDR and mVDR but linearly decrease NaPi-IIb mRNA level. 25
      OH-D3 up-regulates the above gene transcription.

PMID- 29325127
TI  - Inhibiting trophoblast PAR-1 overexpression suppresses sFlt-1-induced anti
      angiogenesis and abnormal vascular remodeling: a possible therapeutic approach
      for preeclampsia.
AB  - STUDY QUESTION: Is it possible to improve vascular remodeling by inhibiting the
      excessive expression of protease-activated receptor 1 (PAR-1) in trophoblast of
      abnormal placenta? SUMMARY ANSWER: Inhibition of trophoblast PAR-1 overexpression
      may promote placental angiogenesis and vascular remodeling, offering an
      alternative therapeutic approach for preeclampsia. WHAT IS KNOWN ALREADY: PAR-1
      is high-affinity receptor of thrombin. Thrombin increases sFlt-1 secretion in
      trophoblast via the activation of PAR-1. It is reported that the expression of
      both thrombin and PAR-1 expression are increased in placentas of preeclampsia
      patients compared with normal placentas. STUDY DESIGN, SIZE, DURATION:
      Trophoblast cells were transfected with PAR-1 short hairpin RNA (shRNA) or PAR-1
      overexpression plasmids in vitro. Tube formation assays and a villus-decidua co
      culture system were used to study the effect of PAR-1 inhibition on placental
      angiogenesis and vascular remodeling, respectively. Placentas from rats with
      preeclampsia were transfected with PAR-1 shRNA to confirm the effect of
      inhibiting PAR-1 overexpression in placenta. PARTICIPANTS/MATERIALS, SETTING,
      METHODS: The trophoblast cell line HTR-8/SVneo was transfected with PAR-1 shRNA
      or PAR-1 overexpression plasmids. After 48 h, supernatant was collected and the
      level of sFlt-1 secretion was measured by ELISA. Human umbilical cord epithelial
      cells and a villus-decidua co-culture system were treated with conditioned media
      to study the effect of PAR-1 inhibition on tube formation and villi vascular
      remodeling. A preeclampsia rat model was established by intraperitoneal injection
      of L-NAME. Plasmids were injected into the placenta of the preeclampsia rats and
      systolic blood pressure was measured on Days 15 and 19. The effect of different
      treatments was evaluated by proteinuria, placental weights, fetal weights and
      fetal numbers in study and control groups. The level of serum sFlt-1 in rats with
      preeclampsia was also measured. Changes in the placenta microvessels were studied
      by histopathological staining. MAIN RESULTS AND THE ROLE OF CHANCE: PAR-1 shRNA
      inhibited PAR-1 expression and significantly suppressed sFlt-1 expression in
      trophoblasts. Soluble Flt-1 level in the supernatant was suppressed by PAR-1
      inhibition plasmid transfection and increased by PAR-1 overexpression plasmids
      (46.93 +/- 5.22 vs. 25.21 +/- 4.18 vs. 67.84 +/- 3.58 ng/ml, P < 0.01). Tube
      formation assays showed that conditioned media from shPAR-1 transfected cells
      resulted in an increase in the total number of branching points compared with
      that of blank controls (P < 0.05). The villus-decidua co-culture system confirmed
      down-regulation of PAR-1 was conducive to angiogenesis and vascular remodeling.
      Transfecting placenta with PAR-1 shRNA plasmids improved placental vascular
      development and ameliorated the symptoms of preeclampsia in rats. After treatment
      with shRNA, blood pressure was controlled (140.83 +/- 1.08 vs. 123.6 +/- 1.47
      mmHg, P < 0.001) and proteinuria levels were decreased (4.48 +/- 0.36 vs. 2.64 +/
      0.25 MUg/MUl, P < 0.01). sFlt-1 protein levels were significantly higher in
      preeclampsia group than in the control group (1.44 +/- 0.33 vs. 2.92 +/- 0.85
      ng/ml, P < 0.001), but was reduced (0.92 +/- 0.06 ng/ml, vs. PE, P < 0.001) in
      the treatment group. The histopathological changes of the placental microvessels
      showed that in the preeclampsia group, the number of blood vessels was reduced,
      while in treatment group, the placental microvasculature was improved (P <
      0.001). LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Despite our
      promising results, the evaluation of kidney damage was studied only by
      proteinuria measurement. Histochemistry of kidney damage will be supplemented in
      a further study. WIDER IMPLICATIONS OF THE FINDINGS: The data showed that
      inhibition of trophoblast PAR-1 overexpression may promote placental angiogenesis
      and vascular remodeling, potentially offering an alternative therapeutic approach
      for preeclampsia. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by
      grants from the National Natural Science Foundation of China (Grant Nos. 81100442
      and 81771605 for Y.Z. and 81179584 for L.Z.) and the Hubei Province Health and
      Family Planning Scientific Research Project (Grant No. WJ2017 M093 for Y.Z.). The
      authors declare that there is no conflict of interest.

PMID- 29325126
TI  - Automated Integration of Trees and Traits: A Case Study Using Paired Fin Loss
      Across Teleost Fishes.
AB  - Data synthesis required for large-scale macroevolutionary studies is challenging
      with the current tools available for integration. Using a classic question
      regarding the frequency of paired fin loss in teleost fishes as a case study, we
      sought to create automated methods to facilitate the integration of broad-scale
      trait data with a sizable species-level phylogeny. Similar to the evolutionary
      pattern previously described for limbs, pelvic and pectoral fin reduction and
      loss are thought to have occurred independently multiple times in the evolution
      of fishes. We developed a bioinformatics pipeline to identify the presence and
      absence of pectoral and pelvic fins of 12,582 species. To do this, we integrated
      a synthetic morphological supermatrix of phenotypic data for the pectoral and
      pelvic fins for teleost fishes from the Phenoscape Knowledgebase (two
      presence/absence characters for 3047 taxa) with a species-level tree for teleost
      fishes from the Open Tree of Life project (38,419 species). The integration
      method detailed herein harnessed a new combined approach by utilizing data based
      on ontological inference, as well as phylogenetic propagation, to reduce overall
      data loss. Using inference enabled by ontology-based annotations, missing data
      were reduced from 98.0% to 85.9%, and further reduced to 34.8% by phylogenetic
      data propagation. These methods allowed us to extend the data to an additional
      11,293 species for a total of 12,582 species with trait data. The pectoral fin
      appears to have been independently lost in a minimum of 19 lineages and the
      pelvic fin in 48. Though interpretation is limited by lack of phylogenetic
      resolution at the species level, it appears that following loss, both pectoral
      and pelvic fins were regained several (3) to many (14) times respectively.
      Focused investigation into putative regains of the pectoral fin, all within one
      clade (Anguilliformes), showed that the pectoral fin was regained at least twice
      following loss. Overall, this study points to specific teleost clades where
      strategic phylogenetic resolution and genetic investigation will be necessary to
      understand the pattern and frequency of pectoral fin reversals.

PMID- 29325129
TI  - Transaortic septal myectomy using direct septal echography.
AB  - We applied direct septal echography in transaortic septal myectomy for left
      ventricular outflow tract obstruction due to hypertrophic obstructive
      cardiomyopathy and asymmetric septal hypertrophy. A small L-shaped probe was
      inserted into the right ventricle through a 2-cm incision on the right
      ventricular outflow tract. The probe was placed directly on the interventricular
      septum to visualize its actual thickness. It was also helpful to push and expose
      the septum into a direct field of vision through the aortic annulus. This type of
      direct septal echography can be useful for the successful performance of
      transaortic septal myectomy.

PMID- 29325128
TI  - Relationship Between 12 Adipocytokines and Distinct Components of the Metabolic
      Syndrome.
AB  - Objective: Adipose tissue-derived signals potentially link obesity and adipose
      tissue dysfunction with metabolic and cardiovascular diseases. Although some
      adipocytokines have been closely related to metabolic and cardiovascular traits,
      it is unknown which adipocytokine or adipocytokine clusters serve as meaningful
      markers of metabolic syndrome (MS) components. Therefore, this study investigated
      the associations of 12 adipocytokines with components of the MS to identify the
      most relevant cytokines potentially related to specific metabolic profiles.
      Research Design and Methods: Twelve cytokines [adiponectin, adipocyte fatty acid
      binding protein (AFABP), angiopoietin-related growth factor, chemerin, fibroblast
      growth factor (FGF) 19, FGF21, FGF23, insulin-like growth factor-1, interleukin
      10, irisin, progranulin, and vaspin] were quantified in a cross-sectional cohort
      of 1046 subjects. Hypothesis-free cluster analysis, multivariate regression
      analyses with parameters of the MS, and discriminant analysis were performed to
      assess associations and the relative importance of each cytokine for reflecting
      MS and its components. Results: Among the studied adipocytokines, adiponectin,
      AFABP, chemerin, and FGF21 showed the strongest associations with MS and several
      MS components in discriminant analyses and multiple regression models. For
      certain metabolic components, these adipocytokines were better discriminators
      than routine metabolic markers. Other cytokines investigated in the present
      cohort are less able to distinguish between metabolically healthy and unhealthy
      subjects. Conclusions: Adiponectin, AFABP, chemerin, and FGF21 showed the
      strongest associations with MS components in a general population, suggesting
      that adverse adipose tissue function is a major contributor to these metabolic
      abnormalities. Future prospective studies should address the question whether
      these adipocytokines can predict the development of metabolic disease states.

PMID- 29325130
TI  - Emergent heterogeneous microenvironments in biofilms: substratum surface
      heterogeneity and bacterial adhesion force-sensing.
AB  - Phenotypically heterogeneous microenvironments emerge as biofilms mature across
      different environments. Phenotypic heterogeneity in biofilm sub-populations not
      obeying quorum sensing-dictated, collective group behavior may be considered as a
      strategy allowing non-conformists to survive hostile conditions. Heterogeneous
      phenotype development has been amply studied with respect to gene expression and
      genotypic changes, but 'biofilm genes' responsible for preprogrammed development
      of heterogeneous microenvironments in biofilms have never been discovered.
      Moreover, the question of what triggers the development of phenotypically
      heterogeneous microenvironments has never been addressed. The definition of
      biofilms as 'surface-adhering and surface-adapted' microbial communities contains
      the word 'surface' twice. This leads us to hypothesize that phenotypically
      heterogeneous microenvironments in biofilms develop as an adaptive response of
      initial colonizers to their adhering state, governed by the forces through which
      they adhere to a substratum surface. No surface is entirely homogeneous, while
      adhering bacteria can substantially contribute to stochastically occurring
      surface heterogeneity. Accordingly, bacterial adhesion forces sensed by initial
      colonizers differ across a substratum surface, leading to differential mechanical
      deformation of the cell wall and membrane, where many environmental sensors are
      located. Bacteria directly adhering to heterogeneous substratum domains therewith
      formulate their own local responses to their adhering state and command non
      conformist behavior, leading to phenotypically heterogeneous microenvironments in
      biofilms.

PMID- 29325131
TI  - Crystal structures of high-pressure phases formed in Si by laser irradiation.
AB  - Internal modification induced in Si by a permeable pulse laser was investigated
      by transmission electron microscopy. A laser induced modified volume (LIMV) was a
      cylindrical rod along the track of a laser beam with the head at the focus of the
      laser beam. In the LIMV, beside voids, dislocations, micro-cracks and what had
      been supposed to be an unidentified high-pressure phase (hpp) of Si were observed
      in LIMV. The so-called 'hpp' was identified mostly as diamond Si.

PMID- 29325132
TI  - Dark tea extract mitigates hematopoietic radiation injury with antioxidative
      activity.
AB  - The hematopoietic system is widely studied in radiation research. Tea has been
      proved to have antioxidative activity. In the present study, we describe the
      protective effects of dark tea extract (DTE) on radiation-induced hematopoietic
      injury. DTE administration significantly enhanced the survival rate of mice after
      7.0 and 7.5 Gy total body irradiation (TBI). The results showed that DTE not only
      markedly increased the numbers and cloning potential of hematopoietic cells, but
      also decreased DNA damages after mice were exposed to 6.0 Gy total body
      irradiation (TBI). In addition, DTE also decreased the levels of reactive oxygen
      species (ROS) in hematopoietic cells by inhibiting NOX4 expression and increasing
      the dismutase, catalase and glutathione peroxidase in livers. These data
      demonstrate that DTE can prevent radiation-induced hematopoietic syndromes, which
      is beneficial for protection from radiation injuries.

PMID- 29325133
TI  - The Efficacy of 24-Month Metformin for Improving Menses, Hormones, and Metabolic
      Profiles in Polycystic Ovary Syndrome.
AB  - Context: The long-term effects of metformin in women with polycystic ovarian
      syndrome (PCOS) are inadequately studied. Objective: The effects of metformin on
      women with PCOS during 24 months with respect to menses, hormones, and metabolic
      profiles are assessed. Design: Prospective cohort. Setting: A reproductive
      endocrinology clinic in a university-affiliated medical center. Patients: One
      hundred nineteen women with PCOS, defined by the Rotterdam criteria, were
      enrolled. Intervention: Metformin was given daily for 24 months. Main Outcome
      Measures: The primary outcome was the proportion of patients with regular
      menstruation during treatment. Changes in anthropometric, hormonal, and metabolic
      parameters were also assessed. Analyses were performed using segmented regression
      analysis with a generalized estimating equation methodology. Outcomes are
      expressed as magnitude of change from the baseline. Results: Both overweight (OW)
      and normal-weight (NW) women with PCOS had increased menstrual frequency and
      decreased body mass index (BMI), testosterone, and luteinizing hormone levels in
      the first 6 months. Further stratification showed that NW women exhibiting
      elevated testosterone at baseline had the largest magnitude of improvement at 6
      months [odds ratio (OR), 7.21; 95% confidence interval (CI), 2.35 to 22.17],
      whereas OW patients with normal testosterone were most likely to achieve normal
      menses at 12 months (OR, 0.63; 95% CI, 0.47 to 0.77). Conclusions: Metformin was
      associated with improvements in the menstrual cycle and most hormonal profiles in
      OW and NW women with PCOS during 24 months of treatment. Most parameters reached
      maximal response and steady-state after 6 months. Phenotypic differences in
      baseline BMI and testosterone level can be used as patient selection criteria or
      treatment prognostics.

PMID- 29325134
TI  - Continued propagation of the CRF19_cpx variant among HIV-positive MSM patients in
      Spain.
AB  - Objectives: The HIV-1 CRF19_cpx genetic form has been recently associated with
      greater pathogenicity. We used CoRIS, a national cohort of 31 reference hospitals
      in Spain, to investigate the current epidemiological situation of this variant in
      Spain. Patients and methods: We analysed 4734 naive HIV-1-positive patients
      diagnosed during the 2007-15 period with an available pol gene sequence in the
      CoRIS resistance database. HIV-1 CRF19_cpx was ascribed through REGA3.0 and
      confirmed by a phylogenetic analysis. We analysed the presence of the
      transmission clusters of HIV-1 CRF19_cpx by maximum likelihood [with the
      randomized accelerated maximum likelihood (RAxML) program] and the time to the
      most recent common ancestor using Bayesian inference (BEAST, v. 1.7.5). Results:
      Nineteen patients were infected with CRF19_cpx: all were male, they had a mean
      age of 42.9 years (95% CI: 36.4-52.5 years), the majority were MSM [n = 18 (95%)]
      and of Spanish nationality [n = 16 (84.2%)] and they had high CD4+ T cell counts
      (~415 cells/mm3). Fifteen patients were grouped into four different transmission
      clusters: two clusters (two patients each) grouped the patients from Valencia and
      another cluster grouped one patient from Madrid and another from Seville. We
      found a larger cluster that grouped nine patients from southern Spain (Malaga and
      Seville), of which six presented mutation G190A. We estimated the origin of all
      the transmission clusters to take place between 2009 and 2010. Conclusions: We
      demonstrate that this variant has spread in Spain in recent years among young HIV
      positive MSM and we note a recent expansion in southern Spain in patients who
      carry mutation G190A. We alert healthcare managers to enhance preventive measures
      to prevent the continuous spread of HIV-1 CRF19_cpx.

PMID- 29325135
TI  - Precipitation is not limiting for xylem formation dynamics and vessel development
      in European beech from two temperate forest sites.
AB  - We investigated the dynamics of xylem differentiation processes and vessel
      characteristics in Fagus sylvatica L. to evaluate the plasticity of xylem
      structures under different environmental conditions. In 2008-10, analyses were
      performed on microcores collected weekly from two temperate sites: Menina planina
      (1200 m above sea level (a.s.l.)) and Panska reka (400 m a.s.l.). The duration
      between the onset and end of major cell differentiation steps and vessel
      characteristics (i.e., density, VD; mean diameter, MVD; mean area, MVA; and
      theoretic conductivity area, TCA) were analysed in the first and last quarters of
      the xylem rings, also in respect of local weather conditions (precipitation,
      temperature). Although the onset, duration and end of xylem formation phases
      differed between the two sites, the time spans between the successive wood
      formation phases were similar. Significant differences in MVD, MVA and TCA values
      were found between the first and last quarters of xylem increment, regardless of
      the site and year. Vessel density, on the other hand, depended on xylem-ring
      width and differed significantly between the sites, being about 30% higher at the
      high elevation site, in beech trees with 54% narrower xylem rings. Vessel density
      in the first quarter of the xylem ring showed a positive correlation with the
      onset of cell expansion, whereas a negative correlation of VD with the cessation
      of cell production was found in the last quarter of xylem increment. This may be
      explained by year-to-year differences in the timing of cambial reactivation and
      leaf development, which effect hormonal regulation of radial growth. No
      significant linkage between intra-annual weather conditions and conduit
      characteristics was found. It can thus be presumed that precipitation is not a
      limiting factor for xylem growth and cell differentiation in beech at the two
      temperate study sites and sites across Europe with similar weather conditions.

PMID- 29325136
TI  - Haemodynamic performance of AFX and Nellix endografts: a computational fluid
      dynamics study.
AB  - OBJECTIVES: The objective of this study is to analyse the flow conditions in the
      AFX and Nellix endografts (EGs) accounting for their postimplantation
      configuration in patients with an endovascular aneurysm repair-treated abdominal
      aortic aneurysm. METHODS: We reconstructed post-endovascular aneurysm repair
      computed tomography scans of patients treated with an AFX or Nellix EG creating
      post-implantation EG models. We examined 16 patients, 8 in each group. The blood
      flow properties were obtained by computational fluid dynamics simulations and
      were subsequently compared with physiological infrarenal blood flow properties
      measured in 5 healthy subjects. Specifically, pressure drop, maximum velocity and
      wall shear stress were measured at peak systole and mean helicity at mid
      diastole. RESULTS: Our statistical analyses showed that the haemodynamic
      properties in both control regions did not vary statistically after the
      implantation of either the AFX or the Nellix EG, except for helicity that was
      significantly lower in the abdominal part of the Nellix EG compared with the
      expected physiological measurement. Regardless of the overall blood flow
      restoration, it is important to note that low pressure drop was detected along
      the limbs of the AFX and suppressed blood helical motion was detected at the
      entrance of the Nellix device. CONCLUSIONS: It is observed from the results that
      the AFX EG has achieved absolute restoration of blood flow after endovascular
      aneurysm repair, although the development of secondary flow in the upper part of
      the EG and the low pressure drop in its limbs should be acknowledged. The Nellix
      EG also seems to be haemodynamically efficient. However, the suppression of
      helical flow before blood enters the device might raise concerns about its
      clinical application.

PMID- 29325137
TI  - Review of Neurosurgery Medical Professional Liability Claims in the United
      States.
AB  - BACKGROUND: Due to disparaging costs and rates of malpractice claims in
      neurosurgery, there has been significant interest in identifying high-risk
      specialties, types of malpractice claims, and characteristics of claim-prone
      physicians. OBJECTIVE: To characterize the malpractice claims against
      neurosurgeons. METHODS: This was a comprehensive analysis of all malpractice
      liability claims involving a neurosurgeon as the primary defendant, conducted
      using the Physician Insurers Association of America Data Sharing Project from
      January 1, 2003 and December 31, 2012. RESULTS: From 2003 to 2012, 2131 closed
      malpractice claims were filed against a neurosurgeon. The total amount of
      indemnity paid collective between 1998 to 2002, 2003 to 2007, and 2008 to 2012
      was $109 614 935, $140 031 875, and $122 577 230, respectively. Of all the
      neurosurgery claims, the most prevalent chief medical factor was improper
      performance (42.1%, $124 943 933), presenting medical condition was
      intervertebral disc disorder (20.6%, $54 223 206), and operative procedure
      performed involved the spinal cord and/or spinal canal (21.0%, $62 614 995).
      Eighty-five (22.91%) of the total neurosurgery claims resulted in patient death,
      resulting in $32 067 759 paid. Improper performance of the actual procedure was
      the most prevalent and highest total paid cause for patient death ($9 584 519).
      CONCLUSION: From 2003 to 2012, we found that neurosurgery malpractice claims rank
      among one of the most costly and prevalent, with the average indemnities paid
      annually and the overall economic burden increasing. Diagnoses and procedures
      involving the spine, along with improper performance, were the most prevalent
      malpractice claims against neurosurgeons. Continued medical malpractice reform is
      essential to correct the overall health care cost burdens, and ultimately improve
      patient safety.

PMID- 29325139
TI  - Does oxidative stress contribute to adverse outcomes in HIV-associated TB?
AB  - In HIV infection, oxidative stress is a pronounced phenomenon, with likely links
      to HIV-related pathologies and the progression of HIV infection per se. TB is an
      AIDS-defining condition. HIV-associated oxidative stress, like that associated
      with diabetes mellitus, might adversely impact the outcomes of TB, probably
      through increased propensity for generation of metabolically dormant
      mycobacterial persisters, alongside other mechanisms. This hypothesis might help
      in guiding the exploration of relevant research directions to improve the care of
      patients.

PMID- 29325138
TI  - Evidence for Viral Interference and Cross-reactive Protective Immunity Between
      Influenza B Virus Lineages.
AB  - Background: Two influenza B virus lineages, B/Victoria and B/Yamagata,
      cocirculate in the human population. While the lineages are serologically
      distinct, cross-reactive responses to both lineages have been detected. Viral
      interference describes the situation whereby infection with one virus limits
      infection and replication of a second virus. We investigated the potential for
      viral interference between the influenza B virus lineages. Methods: Ferrets were
      infected and then challenged 3, 10, or 28 days later with pairs of influenza
      B/Victoria and B/Yamagata viruses. Results: Viral interference occurred at
      challenge intervals of 3 and 10 days and occasionally at 28 days. At the longer
      interval, shedding of challenge virus was reduced, and this correlated with cross
      reactive interferon gamma responses from lymph nodes from virus-infected animals.
      Viruses from both lineages could prevent or significantly limit subsequent
      infection with a virus from the other lineage. Coinfections were rare, indicating
      the potential for reassortment between lineages is limited. Conclusions: These
      data suggest that innate and cross-reactive immunity mediate viral interference
      and that this may contribute to the dominance of a specific influenza B virus
      lineage in any given influenza season. Furthermore, infection with one influenza
      B virus lineage may be beneficial in protecting against subsequent infection with
      either influenza B virus lineage.

PMID- 29325140
TI  - Optimism for the Future in Younger and Older Adults.
AB  - Objectives: Research has suggested that older adults are less optimistic about
      their future than younger adults; however, a limitation of prior studies is that
      younger and older adults were forecasting to different ages and stages of life.
      To address this, we investigated whether there are age differences in future
      optimism when people project to the exact same age. We also tested whether
      optimism differs when projecting one's own future versus another person's future.
      Method: Participants were 285 younger and 292 older adults recruited from Amazon
      Mechanical Turk. Participants completed writing and word-rating tasks in which
      they imagined their own future in 15 years, their own future at age 85, or the
      average person's future at age 85. Results: Younger adults were more optimistic
      than older adults about their own future in 15 years. In contrast, both age
      groups were similarly optimistic about their future at age 85 and expected it to
      be more positive than others' future at age 85. Discussion: Contrary to previous
      research, younger and older adults had comparable future forecasts when
      projecting to the exact same age. These findings emphasize the need to consider
      age and stage of life when examining age differences in future optimism.

PMID- 29325142
TI  - The effect of measuring serum doxycycline concentrations on clinical outcomes
      during treatment of chronic Q fever.
AB  - Background: First choice treatment for chronic Q fever is doxycycline plus
      hydroxychloroquine. Serum doxycycline concentration (SDC) >5 MUg/mL has been
      associated with a favourable serological response, but the effect on clinical
      outcomes is unknown. Objectives: To assess the effect of measuring SDC during
      treatment of chronic Q fever on clinical outcomes. Methods: We performed a
      retrospective cohort study, to assess the effect of measuring SDC on clinical
      outcomes in patients treated with doxycycline and hydroxychloroquine for chronic
      Q fever. Primary outcome was the first disease-related event (new complication or
      chronic Q fever-related mortality); secondary outcomes were all-cause mortality
      and PCR-positivity. Multivariable analysis was performed with a Cox proportional
      hazards model, with shared-frailty terms for different hospitals included.
      Results: We included 201 patients (mean age 68 years, 83% male): in 167 patients
      (83%) SDC was measured, 34 patients (17%) were treated without SDC measurement.
      First SDC was >5 MUg/mL in 106 patients (63%), all with 200 mg doxycycline daily.
      In patients with SDC measured, dosage was adjusted in 41% (n = 68), concerning an
      increase in 64 patients. Mean SDC was 4.1 MUg/mL before dosage increase, and 5.9
      MUg/mL afterwards. SDC measurement was associated with a lower risk for disease
      related events (HR 0.51, 95% CI 0.26-0.97, P = 0.04), but not with all-cause
      mortality or PCR-positivity. Conclusions: SDC measurement decreases the risk for
      disease-related events, potentially through more optimal dosing or improved
      compliance. We recommend measurement of SDC and striving for SDC >5 MUg/mL and
      <10 MUg/mL during treatment of chronic Q fever.

PMID- 29325141
TI  - LncMAP: Pan-cancer atlas of long noncoding RNA-mediated transcriptional network
      perturbations.
AB  - Gene regulatory network perturbations contribute to the development and
      progression of cancer, however, molecular determinants that mediate
      transcriptional perturbations remain a fundamental challenge for cancer biology.
      We show that transcriptional perturbations are widely mediated by long noncoding
      RNAs (lncRNAs) via integration of genome-wide transcriptional regulation with
      paired lncRNA and gene expression profiles. Systematic construction of an LncRNA
      Modulator Atlas in Pan-cancer (LncMAP) reveals distinct types of lncRNA
      regulatory molecules, which are expressed in multiple tissues, exhibit higher
      conservation. Strikingly, cancers with similar tissue origin share lncRNA
      modulators which perturb the regulation of cell cycle and immune response-related
      functions. Furthermore, we identified a large number of pan-cancer lncRNA
      modulators with potential clinical significance, which are differentially
      expressed in cancer or are strongly correlated with drug sensitivity across cell
      lines. Further stratification of cancer patients based on lncRNA-mediated
      transcriptional perturbations identifies subtypes with distinct survival rates.
      Finally, we made a user-friendly web interface available for exploring lncRNA
      mediated transcriptional perturbations across cancer types. Our study provides a
      systems-level dissection of lncRNA-mediated regulatory perturbations in cancer,
      and also presents a valuable tool and resource for investigating the function of
      lncRNAs in cancer.

PMID- 29325143
TI  - Associations of Gross Motor Delay, Behavior, and Quality of Life in Young
      Children With Autism Spectrum Disorder.
AB  - Background: Young children with autism spectrum disorder (ASD) often have gross
      motor delays that may accentuate problem daytime behavior and health-related
      quality of life (QoL). Objective: The objective of this study was to describe the
      degree of gross motor delays in young children with ASD and associations of gross
      motor delays with problem daytime behavior and QoL. The primary hypothesis was
      that Gross motor delays significantly modifies the associations between
      internalizing or externalizing problem daytime behavior and QoL. Design: This
      study used a cross-sectional, retrospective analysis. Methods: Data from 3253
      children who were 2 to 6 years old and who had ASD were obtained from the Autism
      Speaks Autism Treatment Network and analyzed using unadjusted and adjusted linear
      regression. Measures included the Vineland Adaptive Behavior Scales, 2nd edition,
      gross motor v-scale score (VABS-GM) (for Gross motor delays), the Child Behavior
      Checklist (CBCL) (for Problem daytime behavior), and the Pediatric Quality of
      Life Inventory (PedsQL) (for QoL). Results: The mean VABS-GM was 12.12 (SD =
      2.2), representing performance at or below the 16th percentile. After adjustment
      for covariates, the internalizing CBCL t score decreased with increasing VABS-GM
      (beta = - 0.64 SE = 0.12). Total and subscale PedsQL scores increased with
      increasing VABS-GM (for total score: beta = 1.79 SE = 0.17; for subscale score:
      beta = 0.9-2.66 SE = 0.17-0.25). CBCL internalizing and externalizing t scores
      decreased with increasing PedsQL total score (beta = - 0.39 SE = 0.01; beta = -
      0.36 SE = 0.01). The associations between CBCL internalizing or externalizing t
      scores and PedsQL were significantly modified by VABSGM (beta = - 0.026 SE =
      0.005]; beta = - 0.019 SE = 0.007). Limitations: The study lacked ethnic and
      socioeconomic diversity. Measures were collected via parent report without
      accompanying clinical assessment. Conclusions: Cross motor delay was
      independently associated with Problem daytime behavior and QoL in children with
      ASD. Gross motor delay modified the association between Problem daytime behavior
      and QoL. Children with ASD and co-occurring internalizing Problem daytime
      behavior had greater Gross motor delays than children without internalizing
      Problem daytime behavior; therefore, these children may be most appropriate for
      early physical therapist evaluation.

PMID- 29325144
TI  - A Metabolomics Analysis of Body Mass Index and Postmenopausal Breast Cancer Risk.
AB  - Background: Elevated body mass index (BMI) is associated with increased risk of
      postmenopausal breast cancer. The underlying mechanisms, however, remain elusive.
      Methods: In a nested case-control study of 621 postmenopausal breast cancer case
      participants and 621 matched control participants, we measured 617 metabolites in
      prediagnostic serum. We calculated partial Pearson correlations between
      metabolites and BMI, and then evaluated BMI-associated metabolites (Bonferroni
      corrected alpha level for 617 statistical tests = P < 8.10 * 10-5) in relation to
      invasive breast cancer. Odds ratios (ORs) of breast cancer comparing the 90th vs
      10th percentile (modeled on a continuous basis) were estimated using conditional
      logistic regression while controlling for breast cancer risk factors, including
      BMI. Metabolites with the lowest P values (false discovery rate < 0.2) were
      mutually adjusted for one another to determine those independently associated
      with breast cancer risk. Results: Of 67 BMI-associated metabolites, two were
      independently associated with invasive breast cancer risk: 16a-hydroxy-DHEA-3
      sulfate (OR = 1.65, 95% confidence interval [CI] = 1.22 to 2.22) and 3
      methylglutarylcarnitine (OR = 1.67, 95% CI = 1.21 to 2.30). Four metabolites were
      independently associated with estrogen receptor-positive (ER+) breast cancer
      risk: 16a-hydroxy-DHEA-3-sulfate (OR = 1.84, 95% CI = 1.27 to 2.67), 3
      methylglutarylcarnitine (OR = 1.91, 95% CI = 1.23 to 2.96), allo-isoleucine (OR =
      1.76, 95% CI = 1.23 to 2.51), and 2-methylbutyrylcarnitine (OR = 1.89, 95% CI =
      1.22 to 2.91). In a model without metabolites, each 5 kg/m2 increase in BMI was
      associated with a 14% higher risk of breast cancer (OR = 1.14, 95% CI = 1.01 to
      1.28), but adding 16a-hydroxy-DHEA-3-sulfate and 3-methylglutarylcarnitine
      weakened this association (OR = 1.06, 95% CI = 0.93 to 1.20), with the logOR
      attenuating by 57.6% (95% CI = 21.8% to 100.0+%). Conclusion: These four
      metabolites may signal metabolic pathways that contribute to breast
      carcinogenesis and that underlie the association of BMI with increased
      postmenopausal breast cancer risk. These findings warrant further replication
      efforts.

PMID- 29325147
TI  - Trends in Rate of Seizure-Associated Hospitalizations Among Children <5 Years Old
      Before and After Rotavirus Vaccine Introduction in the United Sates, 2000-2013.
AB  - Background: Rotavirus is a common cause of acute gastroenteritis and has also
      been associated with generalized tonic-clonic afebrile seizures. Since rotavirus
      vaccine introduction, hospitalizations for treatment of acute gastroenteritis
      have decreased. We assess whether there has been an associated decrease in
      seizure-associated hospitalizations. Methods: We used discharge codes to abstract
      data on seizure hospitalizations among children <5 years old from the State
      Inpatient Databases of the Healthcare Cost and Utilization Project. We compared
      seizure hospitalization rates before and after vaccine introduction, using
      Poisson regression, stratifying by age and by month and year of admission. We
      performed a time-series analysis with negative binomial models, constructed using
      prevaccine data from 2000 to 2006 and controlling for admission month and year.
      Results: We examined 962899 seizure hospitalizations among children <5 years old
      during 2000-2013. Seizure rates after vaccine introduction were lower than those
      before vaccine introduction by 1%-8%, and rate ratios decreased over time. Time
      series analyses demonstrated a decrease in the number of seizure-coded
      hospitalizations in 2012 and 2013, with notable decreases in children 12-17
      months and 18-23 months. Conclusions: Our analysis provides evidence for a
      decrease in seizure hospitalizations following rotavirus vaccine introduction in
      the United States, with the greatest impact in age groups with a high rotavirus
      associated disease burden and during rotavirus infection season.

PMID- 29325145
TI  - Anxiety-dependent modulation of motor responses to pain expectancy.
AB  - The relationship between pain expectancy and motor system plays a crucial role in
      the human defensive system. Here, we took advantage of the inhibitory modulation
      of the motor pathway to the muscle of the hand receiving painful stimuli, by
      recording motor-evoked potentials (MEPs) to Transcranial Magnetic Stimulation
      (TMS). We employed a classical conditioning paradigm in which neutral (visual and
      auditory) stimuli were conditioned by pairing either painful or not-painful
      stimuli (electric shocks) in separated groups. Only the Pain Group showed clear
      motor responses: i.e. a significant decrease in MEPs amplitude, with respect to
      the neutral condition, not only in conditioning stimuli, when actual shocks were
      paired with neutral stimuli, but also in conditioned stimuli, when shocks were
      only expected. Significant differences between the two groups suggest that the
      MEPs decrease is specific for pain expectancy and does not pertain to
      anticipation in general. Furthermore, in the Pain Group, a significant negative
      correlation between physiological responses to conditioned stimuli and the
      participants' anxiety traits was found: the lower the MEPs amplitude, the higher
      the participants' anxiety scores. The present findings suggest that, in order for
      defensive motor responses to occur, actual pain is not necessary; rather, anxiety
      dependent pain expectancy can be sufficient.

PMID- 29325146
TI  - Dramatic Changes in Malaria Population Genetic Complexity in Dielmo and Ndiop,
      Senegal, Revealed Using Genomic Surveillance.
AB  - Dramatic changes in transmission intensity can impact Plasmodium population
      diversity. Using samples from 2 distant time-points in the Dielmo/Ndiop
      longitudinal cohorts from Senegal, we applied a molecular barcode tool to detect
      changes in parasite genotypes and complexity of infection that corresponded to
      changes in transmission intensity. We observed a striking statistically
      significant difference in genetic diversity between the 2 parasite populations.
      Furthermore, we identified a genotype in Dielmo and Ndiop previously observed in
      Thies, potentially implicating imported malaria. This genetic surveillance study
      validates the molecular barcode as a tool to assess parasite population diversity
      changes and track parasite genotypes.

PMID- 29325148
TI  - Effect of dietary beta-alanine supplementation on growth performance, meat
      quality, carnosine content, and gene expression of carnosine-related enzymes in
      broilers.
AB  - The objective of the current study was to investigate the effect of dietary beta
      alanine supplementation on growth performance, meat quality, antioxidant ability,
      carnosine content, and gene expression of carnosine-related enzymes in broiler
      chicks. We randomly assigned 540 1-day-old Arbor Acres broilers to 5 dietary
      treatments supplemented with 0 (control group), 250, 500, 1,000, or 2,000 mg/kg
      of beta-alanine (mg beta-alanine per kg feed). Each treatment included 6
      replicates of 18 birds. The feeding trial lasted for 42 d. Dietary beta-alanine
      supplementation linearly and quadratically increased the average daily gain (ADG)
      during the starting period (d 1 to 21, P = 0.02 and P = 0.002). The feed
      conversion ratio (FCR) decreased quadratically in response to dietary beta
      alanine supplementation during the starting and entire periods (P < 0.001 and P =
      0.003, respectively). For the entire period, the predicted best FCR would be
      achieved when beta-alanine was fed at a level of 1,100 mg/kg from quadratic
      regression. The concentrations of carnosine and beta-alanine in breast muscle
      increased quadratically with dietary beta-alanine supplementation (d 42, P <
      0.001 and P = 0.001, respectively). The predicted dietary beta-alanine level for
      highest breast carnosine content was 1,196 mg/kg. Dietary supplementation with
      beta-alanine reduced the taurine concentrations in plasma (d 42, linear and
      quadratic, P < 0.001). Breast muscle yield increased linearly and quadratically
      in response to dietary beta-alanine addition (d 21, P = 0.017 and P = 0.007).
      Dietary supplementation with beta-alanine quadratically reduced the shear force
      (P = 0.003), whereas a*45 min and a*24 h values increased quadratically in
      response to dietary beta-alanine supplementation (d 42, P = 0.020 and P = 0.021,
      respectively). Dietary beta-alanine addition quadratically enhanced the
      expression of carnosine synthase and taurine transporter mRNAs (P < 0.05).
      Overall, dietary beta-alanine supplementation improved growth performance and
      carnosine content, ameliorated antioxidant capacity and meat quality, and
      upregulated the gene expression of carnosine synthesis-related enzymes in broiler
      chicks.

PMID- 29325149
TI  - Anatomy of a Hotspot: Chain and Seroepidemiology of Ebola Virus Transmission,
      Sukudu, Sierra Leone, 2015-16.
AB  - Studies have yet to include minimally symptomatic Ebola virus (EBOV) infections
      and unrecognized Ebola virus disease (EVD) in Ebola-related transmission chains
      and epidemiologic risk estimates. We conducted a cross-sectional, sero
      epidemiological survey from October 2015 to January 2016 among 221 individuals
      living in quarantined households from November 2014 to February 2015 during the
      Ebola outbreak in the village of Sukudu, Sierra Leone. Of 48 EBOV-infected
      persons, 25% (95% confidence interval [CI], 14%-40%) had minimally symptomatic
      EBOV infections and 4% (95% CI, 1%-14%) were unrecognized EVD cases. The pattern
      of minimally symptomatic EBOV infections in the transmission chain was nonrandom
      (P < .001, permutation test). Not having lived in the same house as an EVD case
      was significantly associated with minimally symptomatic infection. This is the
      first study to investigate a chain of EBOV transmission inclusive of minimally
      symptomatic EBOV infections and unrecognized EVD. Our findings provide new
      insights into Ebola transmission dynamics and quarantine practices.

PMID- 29325150
TI  - The relationship between alcohol use and long-term cognitive decline in middle
      and late life: a longitudinal analysis using UK Biobank.
AB  - Background: Using UK Biobank data, this study sought to explain the causal
      relationship between alcohol intake and cognitive decline in middle and older
      aged populations. Methods: Data from 13 342 men and women, aged between 40 and 73
      years were used in regression analysis that tested the functional relationship
      and impact of alcohol on cognitive performance. Performance was measured using
      mean reaction time (RT) and intra-individual variation (IIV) in RT, collected in
      response to a perceptual matching task. Covariates included body mass index,
      physical activity, tobacco use, socioeconomic status, education and baseline
      cognitive function. Results: A restricted cubic spline regression with three
      knots showed how the linear (beta1 = -0.048, 95% CI: -0.105 to -0.030) and non
      linear effects (beta2 = 0.035, 95% CI: 0.007-0.059) of alcohol use on mean RT and
      IIV in RT (beta1 = -0.055, 95% CI: -0.125 to -0.034; beta2 = 0.034, 95% CI: 0.002
      0.064) were significant adjusting for covariates. Cognitive function declined as
      alcohol use increased beyond 10 g/day. Decline was more apparent as age
      increased. Conclusions: The relationship between alcohol use and cognitive
      function is non-linear. Consuming more than one UK standard unit of alcohol per
      day is detrimental to cognitive performance and is more pronounced in older
      populations.

PMID- 29325151
TI  - The making of virgin fruit: the molecular and genetic basis of parthenocarpy.
AB  - Fruit set-the commitment of an angiosperm plant to develop fruit-is a key
      developmental process that normally occurs following successful fertilization.
      Parthenocarpy arises when fruit automatically develop in the absence of
      fertilization. This review uses parthenocarpic fruit development as a focal
      device through which to recapitulate and understand the molecular effectors that
      mediate and regulate fruit set. The review demonstrates that studies of
      parthenocarpy are providing vital insight into plant development, signaling and,
      potentially, high-value agricultural products.

PMID- 29325152
TI  - Cohort Profile: Health and Ageing in Africa: a Longitudinal Study of an INDEPTH
      Community in South Africa (HAALSI).

PMID- 29325154
TI  - Growth and carbon balance are differently regulated by tree and shoot fruiting
      contexts: an integrative study on apple genotypes with contrasted bearing
      patterns.
AB  - In plants, carbon source-sink relationships are assumed to affect their
      reproductive effort. In fruit trees, carbon source-sink relationships are likely
      to be involved in their fruiting behavior. In apple, a large variability in
      fruiting behaviors exists, from regular to biennial, which has been related to
      the within-tree synchronization vs desynchronization of floral induction in buds.
      In this study, we analyzed if carbon assimilation, availability and fluxes as
      well as shoot growth differ in apple genotypes with contrasted behaviors. Another
      aim was to determine the scale of plant organization at which growth and carbon
      balance are regulated. The study was carried out on 16 genotypes belonging to
      three classes: (i) biennial, (ii) regular with a high production of floral buds
      every year and (iii) regular, displaying desynchronized bud fates in each year.
      Three shoot categories, vegetative and reproductive shoots with or without
      fruits, were included. This study shows that shoot growth and carbon balance are
      differentially regulated by tree and shoot fruiting contexts. Shoot growth was
      determined by the shoot fruiting context, or by the type of shoot itself, since
      vegetative shoots were always longer than reproductive shoots whatever the tree
      crop load. Leaf photosynthesis depended on the tree crop load only, irrespective
      of the shoot category or the genotypic class. Starch content was also strongly
      affected by the tree crop load with some adjustments of the carbon balance among
      shoots since starch content was lower, at least at some dates, in shoots with
      fruits compared with the shoots without fruits within the same trees. Finally,
      the genotypic differences in terms of shoot carbon balance partly matched with
      genotypic bearing patterns. Nevertheless, carbon content in buds and the role of
      gibberellins produced by seeds as well as the distances at which they could
      affect floral induction should be further analyzed.

PMID- 29325153
TI  - Network perturbation analysis of gene transcriptional profiles reveals protein
      targets and mechanism of action of drugs and influenza A viral infection.
AB  - Genome-wide transcriptional profiling provides a global view of cellular state
      and how this state changes under different treatments (e.g. drugs) or conditions
      (e.g. healthy and diseased). Here, we present ProTINA (Protein Target Inference
      by Network Analysis), a network perturbation analysis method for inferring
      protein targets of compounds from gene transcriptional profiles. ProTINA uses a
      dynamic model of the cell-type specific protein-gene transcriptional regulation
      to infer network perturbations from steady state and time-series differential
      gene expression profiles. A candidate protein target is scored based on the gene
      network's dysregulation, including enhancement and attenuation of transcriptional
      regulatory activity of the protein on its downstream genes, caused by drug
      treatments. For benchmark datasets from three drug treatment studies, ProTINA was
      able to provide highly accurate protein target predictions and to reveal the
      mechanism of action of compounds with high sensitivity and specificity. Further,
      an application of ProTINA to gene expression profiles of influenza A viral
      infection led to new insights of the early events in the infection.

PMID- 29325155
TI  - Sleep findings in Brazilian children with congenital Zika syndrome.
AB  - Study Objectives: Zika virus infection during pregnancy may result in congenital
      Zika syndrome (CZS), whose characteristics are being described. Methods: The
      present study aimed to investigate the sleep characteristics of 136
      infants/toddlers (88 with CZS and 48 with typical development (TD), age and
      gender matched, 60% girls and 40% boys in both groups) using the Brief Infant
      Sleep Questionnaire. The ages of children in both groups ranged from 5 to 24
      months (CZS 15.9 +/- 0.4 vs. TD 15.8 +/- 1.0 months, P= 0.90). Results: The
      results show that 34.1% of CZS and 2% of TD children were defined as poor
      sleepers, 15% of CZS and 2% of TD children remained awake at night for a period
      longer than 1 hour, and 24% of CZS and 2% of TD children slept less than 9 hours.
      The CZS group showed shorter total sleep time (CZS 11.24 +/- 2.6 vs. TD 12.02 +/-
      1.9 hours, P= 0.03) and shorter nocturnal sleep duration than the TD group (CZS
      8.2 +/- 0.2 vs. TD 9.4 +/- 0.2 hours, P= 0.0002). In contrast to the control
      group (P= 0.02, r= -0.34), in the CZS group, no correlation was found between age
      and nocturnal wakefulness. Future studies should explore these data in relation
      to the development and maturation of the central nervous system of these
      children. Conclusions: Considering the well-known consequences of poor sleep
      quality on health in several populations, the presence of sleep disorders should
      be considered in CZS using multidisciplinary treatments.

PMID- 29325156
TI  - Using Metabolomics to Explore the Role of Postmenopausal Adiposity in Breast
      Cancer Risk.

PMID- 29325157
TI  - A National Imperative: Multimodal Pain Education Reform in US Medical Schools.

PMID- 29325158
TI  - Influence of light sources and photoperiod on growth performance, carcass
      characteristics, and health indices of broilers grown to heavy weights.
AB  - Effects of light sources and photoperiod on growth performance, carcass
      characteristics and health indices of broilers were investigated in 4 trials. In
      each trial, 720 1-day-old Ross * Ross 708 chicks were randomly distributed into
      12 environmentally controlled rooms (30 males/30 females/room). The experimental
      design was a 4 * 3 factorial treatments consisted of 4 light sources
      [incandescent (ICD, standard), compact fluorescent (CFL), neutral light-emitting
      diode (Neutral-LED), and cool poultry-specific filtered LED (Cool-PSF-LED)] and 3
      photoperiods [long/continuous (23L:1D), regular/intermittent (2L:2D), and
      short/non-intermittent (8L:16D)] from d8-d56. Birds were fed the same diet, while
      feed and water were provided ad libitum. Birds and feed were weighed on 1, 14,
      28, 42, and 56 d of age for growth performance. Mortality was recorded daily and
      feed conversion was adjusted for mortality. Immune response was determined on d
      28 to 35, whereas other welfare indices were performed on d 42, 43, and 49. At 56
      d of age, 10 male and 10 female birds from each room were randomly selected and
      processed to determine weights and yields. The BW, BW gain, live weight, and
      carcass weights and yields of birds reared under Cool-PSF-LED were increased (P
      <= 0.05) in comparison to birds reared under ICD, but FI, FCR, and mortality were
      not affected. Moreover, broilers subjected to the short/non-intermittent
      photoperiod had the lowest (P <= 0.05) BW, BW gain, FI, live weight, carcass
      weight, and pectoralis major and minor weights compared to other 2 photoperiods.
      There was no effect of treatments on some carcass characteristics. There was no
      effect of treatments on welfare indices, suggesting that the light sources
      evaluated did not compromise welfare of heavy broilers. It was concluded that the
      3 light sources evaluated in this study may be suitable for replacement of ICD
      light source along with regular/intermittent photoperiod instead of
      long/continuous photoperiod in poultry facilities to save energy utilization,
      thereby reducing the total cost of production.

PMID- 29325159
TI  - A Novel Rice Xylosyltransferase Catalyzes the Addition of 2-O-Xylosyl Side Chains
      onto the Xylan Backbone.
AB  - Xylan is a major hemicellulose in both primary and secondary walls of grass
      species. It consists of a linear backbone of beta-1,4-linked xylosyl residues
      that are often substituted with monosaccharides and disaccharides. Xylosyl
      substitutions directly on the xylan backbone have not been reported in grass
      species, and genes responsible for xylan substitutions in grass species have not
      been well elucidated. Here, we report functional characterization of a rice
      (Oryza sativa) GT61 glycosyltransferase, XYXT1 (xylan xylosyltransferase1), for
      its role in xylan substitutions. XYXT1 was found to be ubiquitously expressed in
      different rice organs and its encoded protein was targeted to the Golgi, the site
      for xylan biosynthesis. When expressed in the Arabidopsis gux1/2/3 triple mutant,
      in which xylan was completely devoid of sugar substitutions, XYXT1 was able to
      add xylosyl side chains onto xylan. Glycosyl linkage analysis and comprehensive
      structural characterization of xylooligomers generated by xylanase digestion of
      xylan from transgenic Arabidopsis plants expressing XYXT1 revealed that the side
      chain xylosyl residues were directly attached to the xylan backbone at O-2, a
      substituent not present in wild-type Arabidopsis xylan. XYXT1 was unable to add
      xylosyl residues onto the arabinosyl side chains of xylan when it was co
      expressed with OsXAT2 (Oryza sativa xylan arabinosyltransferase2) in the gux1/2/3
      triple mutant. Furthermore, we showed that recombinant XYXT1 possessed an
      activity transferring xylosyl side chains onto xylooligomer acceptors, whereas
      recombinant OsXAT2 catalyzed the addition of arabinosyl side chains onto
      xylooligomer acceptors. Our findings from both an in vivo gain-of-function study
      and an in vitro recombinant protein activity assay demonstrate that XYXT1 is a
      novel beta-1,2-xylosyltransferase mediating the addition of xylosyl side chains
      onto xylan.

PMID- 29325160
TI  - Implementing Electronic Health Record Default Settings to Reduce Opioid
      Overprescribing: A Pilot Study.
AB  - Objective: To pilot test the effectiveness, feasibility, and acceptability of
      instituting a 15-pill quantity default in the electronic health record for new
      Schedule II opioid prescriptions. Design: A mixed-methods pilot study in two
      health systems, including pre-post analysis of prescribed opioid quantity and
      focus groups or interviews with prescribers and health system administrators.
      Methods: We implemented a 15-pill electronic health record default for new
      Schedule II opioids and assessed opioid quantity before and after implementation
      using electronic health record data on 6,390 opioid prescriptions from 448
      prescribers. We then analyzed themes from focus groups and interviews with four
      staff members and six prescribers. Results: The proportion of opioid
      prescriptions for 15 pills increased at both sites after adding an electronic
      health record default, with one reaching statistical significance (from 4.1% to
      7.2% at CHC, P = 0.280, and 15.9% to 37.2% at WVU, P < 0.001). The proportion of
      15-pill prescriptions increased among high-prescribing departments and among most
      high- and low-frequency prescribers, except for low-frequency prescribers at CHC.
      Sites reported limited challenges in instituting the default, although ease of
      implementation varied by electronic health record vendor. Most prescribers were
      not aware of the default change and stated that they made prescribing decisions
      based on patient clinical characteristics rather than defaults. Conclusions: This
      pilot provides initial evidence that changing default settings can increase the
      number of prescriptions at the default level. This low-cost and relatively simple
      intervention could have an impact on opioid overprescribing. However, default
      settings should be selected carefully to avoid unintended consequences.

PMID- 29325161
TI  - Five-Year Antibody Persistence Following a Japanese Encephalitis Chimeric Virus
      Vaccine (JE-CV) Booster in JE-CV-Primed Children in the Philippines.
AB  - Clinical Trials Registration: NCT01190228.

PMID- 29325162
TI  - An Analysis of Adverse Events in the Rehabilitation Department: Using the
      Veterans Affairs Root Cause Analysis System.
AB  - Background: Root cause analyses (RCA) are often completed in health care settings
      to determine causes of adverse events (AEs). RCAs result in action plans designed
      to mitigate future patient harm. National reviews of RCA reports have assessed
      the safety of numerous health care settings and suggested opportunities for
      improvement. However, few studies have assessed the safety of receiving care from
      physical therapists, occupational therapists, or speech and language pathology
      pathologists. Objective: The objective of this study was to determine the types
      of AEs, root causes, and action plans for risk mitigation that exist within the
      disciplines of rehabilitation medicine. Design: This study is a retrospective,
      cross-sectional review. Methods: A national search of the Veterans Health
      Administration RCA database was conducted to identify reports describing AEs
      associated with physical therapy, occupational therapy, or speech and language
      pathology services between 2009 and May 2016. Twenty-five reports met the
      inclusion requirements. The reports were classified by the event type, root
      cause, action plans, and strength of action plans. Results: Delays in care
      (32.0%) and falls (28.0%) were the most common type of AE. Three AEs resulted in
      death. RCA teams identified deficits regarding policy and procedures as the most
      common root cause. Eighty-eight percent of RCA reports included strong or
      intermediate action plans to mitigate risk. Strong action plans included
      standardizing emergency terminology and implementing a dedicated line to call for
      an emergency response. Limitations: These data are self-reported and only AEs
      that are scored as a safety assessment code 3 in the system receive a full RCA,
      so there are likely AEs that were not captured in this study. In addition, the
      RCA reports are deidentified and so do not include all patient characteristics.
      As the Veterans Health Administration system services mostly men, the data might
      not generalize to non-Veterans Health Administration systems with a different
      patient mix. Conclusions: Care provided by rehabilitation professionals is
      generally safe, but AEs do occur. Based on this RCA review, the safety of
      rehabilitation services can be improved by implementing strong practices to
      mitigate risk to patients. Checklists should be considered to aid timely decision
      making when initiating an emergency response.

PMID- 29325164
TI  - Sleep duration in the United States 2003-2016: first signs of success in the
      fight against sleep deficiency?
AB  - Study Objectives: The high prevalence of chronic insufficient sleep in the
      population has been a concern due to the associated health and safety risks. We
      evaluated secular trends in sleep duration over the most recent 14-year period.
      Methods: The American Time Use Survey, representative of US residents >=15 years,
      was used to investigate trends in self-reported sleep duration and waking
      activities for the period 2003-2016 (N = 181335 respondents). Results: Sleep
      duration increased across survey years both on weekdays (+1.40 min/year) and
      weekends (+0.83 min/year, both p < .0001, adjusted models). This trend was
      observed in students, employed respondents, and retirees, but not in those
      unemployed or not in the labor force. On workdays, the prevalence of short (<=7
      hr), average (>7-9 hr), and long (>9 hr) sleep changed by -0.44% per year (p <
      .0001), -0.03% per year (p = .5515), and +0.48% per year (p < .0001),
      respectively. The change in sleep duration was predominantly explained by
      respondents retiring earlier in the evening. The percentage of respondents who
      watched TV or read before bed-two prominent waking activities competing with
      sleep-decreased over the same time period, suggesting that portions of the
      population are increasingly willing to trade time in leisure activities for more
      sleep. The results also suggest that increasing online opportunities to work,
      learn, bank, shop, and perform administrative tasks from home freed up time that
      likely contributed to increased sleep duration. Conclusions: The findings
      indicate first successes in the fight against sleep deficiency. Public health
      consequences of the observed increase in the prevalence of long sleep remain
      unclear and warrant further investigation.

PMID- 29325165
TI  - Utilization of soy hulls, oat hulls, and flax meal fiber in adult broiler breeder
      hens.
AB  - A total of 72, 65-week-old broiler breeder hens (Ross 308, BW 4,190 +/- 45 g) was
      placed in individual cages to investigate utilization of fiber in soy hulls (SH),
      oat hulls (OH), and flax meal (FM). Birds were adapted to cages for 10 d prior to
      allocation (n = 18) to broiler breeder ration (control) or control mixed with
      either of the 3 fiber sources (wt/wt) added to supply equal amounts of neutral
      detergent fiber (NDF) ~21% and TiO2. The daily feed allocation was based on 4%
      BW. Feed intake (FI) was monitored daily, and grab excreta samples were taken on
      d 16 and 17. On d 18, all birds were weighed and killed 2 h post feeding to
      measure ceca digesta pH and short chain fatty acids (SCFA). Relative to the
      control birds, birds receiving fiber lost (P < 0.05) BW due to decreased (P <
      0.05) FI. The BW changes were respectively +80, -174, -133, and -585 g/bird for
      control, SH, OH, and FM, and corresponding FI was 1,062, 918, 885, and 590
      g/bird. Birds fed FM retained higher (P < 0.05) NDF than birds fed either SH or
      OH. The ceca digesta pH was lower (P < 0.05) in birds receiving added fiber
      relative to control. However, ceca digesta pH of FM fed birds was lower (P <
      0.05) than in birds fed either SH or OH, which were in turn similar (P > 0.05).
      Birds fed FM had higher (P < 0.05) concentration of butyric acid than birds fed
      the control diets, while birds fed SH and OH had intermediate butyric acid
      concentration. Acetic acid and total SCFA concentrations were higher (P < 0.05)
      in birds fed OH diet than in birds fed control but was similar (P > 0.05) to that
      in birds fed either SH or FM. In conclusion, short term feeding of fibrous feed
      ingredients reduced BW linked to reduced FI. Fiber sources exhibited differences
      in utilization reflective of chemical characteristics.

PMID- 29325166
TI  - Drug safety and immunogenicity of tumour necrosis factor inhibitors: the story so
      far.
AB  - TNF-alpha inhibitor (TNFi) therapies have transformed the treatment of several
      rheumatic musculoskeletal diseases. However, the majority of TNFi's are
      immunogenic and consequent anti-drug antibodies formation can impact on both
      treatment efficacy and safety. Several controversies exist in the area of
      immunogenicity of TNFis and drug safety. While anti-drug antibodies to TNFis have
      been described in association with infusion reactions; serious adverse events
      (AEs) such as thromboembolic events, lupus-like syndrome, paradoxical AEs, for
      example, vasculitis-like events and other autoimmune manifestations have also
      been reported. The expansion of the biologic armamentarium, new treatment
      strategies such as introduction/switching to biosimilars and cost-saving
      approaches such as TNFi tapering, may all have a potential impact on
      immunogenicity and clinical sequelae. In this review we evaluate how evolution of
      biologics relates to drug safety and immunogenicity, appraise relevant evidence
      from trials, spontaneous pharmacovigilance and observational studies and outline
      the areas of uncertainty that still exist.

PMID- 29325167
TI  - A multicentre study of antifungal susceptibility patterns among 350 Candida auris
      isolates (2009-17) in India: role of the ERG11 and FKS1 genes in azole and
      echinocandin resistance.
AB  - Background: Candida auris has emerged globally as an MDR nosocomial pathogen in
      ICU patients. Objectives: We studied the antifungal susceptibility of C. auris
      isolates (n = 350) from 10 hospitals in India collected over a period of 8 years.
      To investigate azole resistance, ERG11 gene sequencing and expression profiling
      was conducted. In addition, echinocandin resistance linked to mutations in the C.
      auris FKS1 gene was analysed. Methods: CLSI antifungal susceptibility testing of
      six azoles, amphotericin B, three echinocandins, terbinafine, 5-flucytosine and
      nystatin was conducted. Screening for amino acid substitutions in ERG11 and FKS1
      was performed. Results: Overall, 90% of C. auris were fluconazole resistant (MICs
      32 to >=64 mg/L) and 2% and 8% were resistant to echinocandins (>=8 mg/L) and
      amphotericin B (>=2 mg/L), respectively. ERG11 sequences of C. auris exhibited
      amino acid substitutions Y132 and K143 in 77% (n = 34/44) of strains that were
      fluconazole resistant whereas WT genotypes, i.e. without substitutions at these
      positions, were observed in isolates with low fluconazole MICs (1-2 mg/L)
      suggesting that these substitutions confer a phenotype of resistance to
      fluconazole similar to that described for Candida albicans. No significant
      expression of ERG11 was observed, although expression was inducible in vitro with
      fluconazole exposure. Echinocandin resistance was linked to a novel mutation
      S639F in FKS1 hot spot region I. Conclusions: Overall, 25% and 13% of isolates
      were MDR and multi-azole resistant, respectively. The most common resistance
      combination was azoles and 5-flucytosine in 14% followed by azoles and
      amphotericin B in 7% and azoles and echinocandins in 2% of isolates.

PMID- 29325169
TI  - Severe Sepsis and Septic Shock Associated with Chikungunya Fever in an
      Adolescent.
AB  - Chikungunya is usually a benign disease, and little is known on the occurrence of
      severe clinical complications. We describe a 12-year-old boy with rapid onset
      septic shock and multi-organ failure associated with chikungunya fever. Severe
      sepsis and septic shock can be associated with chikungunya.

PMID- 29325170
TI  - Ecology of Paracoccidioides brasiliensis, P. lutzii and related species:
      infection in armadillos, soil occurrence and mycological aspects.
AB  - Paracoccidioides brasiliensis and the related species P. americana, P.
      restrepiensis, P. venezuelensis, and P. lutzii (Ascomycota, Ajellomycetaceae) are
      the etiological agents of paracoccidoidoimycosis (PCM), one of the most important
      systemic mycoses in Latin America. They are dimorphic fungi, with a mycelial life
      cycle in soil and a yeast phase associated with tissues of mammalian hosts. This
      study aimed to detect Paracoccidioides spp. in armadillo tissues and associated
      soil samples in three well-defined geographic areas, including the Alta Floresta,
      an area not only endemic for PCM in the central region of Brazil but also of
      probable P. lutzii occurrence, whose ecology and geographic distribution are
      poorly elucidated. The isolates were genotyped by sequencing ITS-rDNA and the
      gp43-exon-2 region, and by PCR-RFLP of alpha tubulin (tub1) gene; mycological
      aspects such as yeast-to-mycelial transition, growth and conidial production in
      soil extract agar were also evaluated. We confirmed that while armadillos are
      highly infected by P. brasiliensis, including multiple infections by distinct
      genotypes or species (P. brasiliensis and P. americana) in the same animal, the
      same does not hold true for P. lutzii, which in turn seems to present less
      capacity for mycelial growth and conidial production, when developing in a soil
      related condition.

PMID- 29325171
TI  - Maternal and Child Health Handbook use for maternal and child care: a cluster
      randomized controlled study in rural Java, Indonesia.
AB  - Background: Effectiveness of the Maternal and Child Health Handbook (MCHHB), a
      home-based booklet for pregnancy, delivery and postnatal/child health, was
      evaluated on care acquisition and home care in rural Java, a low service-coverage
      area. Methods: We conducted a health centre-based randomized trial, with a 2-year
      follow-up. Intervention included (i) MCHHB provision at antenatal care visits;
      (ii) records and guides by health personnel on and with the MCHHB; and (iii)
      sensitization of care by volunteers using the MCHHB. Results: The follow-up rate
      was 70.2% (183, intervention area; 271, control area). Respondents in the
      intervention area received consecutive MCH services including two doses of
      tetanus toxoid injections and antenatal care four times or more during pregnancy,
      professional assistance during child delivery and vitamin A supplements
      administration to their children, after adjustment for confounding variables and
      cluster effects (OR = 2.03, 95% CI: 1.19-3.47). In the intervention area, home
      care (continued breastfeeding; introducing complementary feeding; proper feeding
      order; varied foods feeding; self-feeding training; and care for cough),
      perceived support by husbands, and lower underweight rates and stunting rates
      among children were observed. Conclusion: MCHHB use promoted continuous care
      acquisition and care at home from pregnancy to early child-rearing stages in
      rural Java.

PMID- 29325172
TI  - PRES: Review of Histological Features.
AB  - Posterior reversible encephalopathy syndrome was described in 1996 as a clinical
      neuroimaging entity characterized by parieto-occipital watershed-region edema
      without overt infarction. It has been linked to hypertension, eclampsia,
      immunosuppressive therapies, infections, and autoimmune disorders. The condition
      usually has an acute onset, presents with seizures, and ameliorates within days.
      There have been few neuropathological studies, but in some cases, tissue damage
      may be more permanent.

PMID- 29325163
TI  - Transethnic Evaluation Identifies Low-Frequency Loci Associated With 25
      Hydroxyvitamin D Concentrations.
AB  - Context: Vitamin D inadequacy is common in the adult population of the United
      States. Although the genetic determinants underlying vitamin D inadequacy have
      been studied in people of European ancestry, less is known about populations with
      Hispanic or African ancestry. Objective: The Trans-Ethnic Evaluation of Vitamin D
      (TRANSCEN-D) genomewide association study (GWAS) consortium was assembled to
      replicate genetic associations with 25-hydroxyvitamin D [25(OH)D] concentrations
      from the Study of Underlying Genetic Determinants of Vitamin D and Highly Related
      Traits (SUNLIGHT) meta-analyses of European ancestry and to identify genetic
      variants related to vitamin D concentrations in African and Hispanic ancestries.
      Design: Ancestry-specific (Hispanic and African) and transethnic (Hispanic,
      African, and European) meta-analyses were performed with Meta-Analysis Helper
      software (METAL). Patients or Other Participants: In total, 8541 African American
      and 3485 Hispanic American (from North America) participants from 12 cohorts and
      16,124 European participants from SUNLIGHT were included in the study. Main
      Outcome Measures: Blood concentrations of 25(OH)D were measured for all
      participants. Results: Ancestry-specific analyses in African and Hispanic
      Americans replicated single nucleotide polymorphisms (SNPs) in GC (2 and 4 SNPs,
      respectively). An SNP (rs79666294) near the KIF4B gene was identified in the
      African American cohort. Transethnic evaluation replicated GC and DHCR7 region
      SNPs. Additionally, the transethnic analyses revealed SNPs rs719700 and rs1410656
      near the ANO6/ARID2 and HTR2A genes, respectively. Conclusions: Ancestry-specific
      and transethnic GWASs of 25(OH)D confirmed findings in GC and DHCR7 for African
      and Hispanic American samples and revealed findings near KIF4B, ANO6/ARID2, and
      HTR2A. The biological mechanisms that link these regions with 25(OH)D metabolism
      warrant further investigation.

PMID- 29325174
TI  - Safety evaluation of zinc methionine in laying hens: Effects on laying
      performance, clinical blood parameters, organ development, and histopathology.
AB  - The study was conducted to investigate whether high-dose zinc methionine (Zn-Met)
      affected the safety of laying hens, including laying performance, hematological
      parameters, serum chemical parameters, organ index, and histopathology. A total
      of 540 20-week-old Hy-Line White laying hens was randomly allocated to 6 groups
      with 6 replicates of 15 birds each. Birds were fed diets supplemented with 0
      (control), 70, 140, 350, 700, or 1,400 mg Zn/kg diet as Zn-Met. The experiment
      lasted for 8 wk after a 2-week acclimation period. Results showed that dietary
      supplementation with 70 or 140 mg Zn/kg diet as Zn-Met significantly increased
      average daily egg mass (ADEM), laying rate (LR), and feed conversion ratio (FCR)
      (P < 0.05) and lowered broken and soft-shelled egg ratio (BSER) (P < 0.05) in
      comparison with the control group; no significant differences were detected among
      hens fed with 0, 350, or 700 mg Zn/kg as Zn-Met (P > 0.05); hens administered
      1,400 mg Zn/kg showed a significant increase in BSER and remarkable decreases in
      ADEM, LR, and FCR (P < 0.001). There were no significant differences among hens
      receiving 0, 70, 140, 350, or 700 mg Zn/kg as Zn-Met in serum chemical parameters
      (P > 0.05); supplementation with 1,400 mg Zn/kg as Zn-Met remarkably elevated the
      concentrations of serum total bilirubin (TBILI), glucose (GLU), uric acid (UA),
      and creatinine (CRE) (P < 0.001), and enhanced activities of serum glutamic
      oxalacetic transaminase (GOP) and alkaline phosphatase (AKP) (P < 0.001) compared
      with the control group. No significant histopathological changes were found in
      hens administered 0, 70, 140, 350, or 700 mg Zn/kg as Zn-Met, while significant
      histological lesions were observed in the heart, liver, lung, and kidney tissues
      of hens receiving 1,400 mg Zn/kg as Zn-Met. No significant differences were
      detected in hematological parameters or organ index (P > 0.05). In conclusion, a
      nominal Zn concentration of 700 mg/kg as Zn-Met is considered to be no-observed
      adverse-effect level following daily administration to hens for 56 days.

PMID- 29325175
TI  - Early Parental Abuse and Daily Assistance to Aging Parents With Disability:
      Associations With the Middle-Aged Adults' Daily Well-being.
AB  - Objectives: The current study examined the within-person association between
      providing daily assistance to aging parents with disability and adult children's
      daily mood in the context of early relationship with parents. Methods: We used
      data from 782 participants and 5,758 daily interviews from the Midlife in the
      United States (MIDUS) Refresher, with 248 people self-reported providing daily
      assistance ranging from 1 to 8 days out of the entire daily-interview period.
      Multilevel models were fit to examine the moderating effect of physical and
      emotional abuse from parents in early life on the associations between daily
      assistance to parents today and yesterday and daily mood. Additional analyses
      were conducted to examine whether the moderating effect of parental abuse
      remained when the assistance was provided for other family members and friends.
      Results: Providing assistance today and yesterday to parents had immediate and
      lagged associations with higher negative affect when adult children experienced
      childhood emotional abuse from parents. No significant findings were found for
      daily positive affect. The moderating effect of parental abuse became
      nonsignificant when the assistance was provided to other family members or
      friends. Discussion: Daily assistance to parents with disability needs to be
      examined in the context of the relationship history with parents. The impact of
      childhood abuse can linger long after the actual incident. Frequent early
      emotional abuse from parents was associated with greater distress when the middle
      aged provided daily assistance to their aging parents.

PMID- 29325173
TI  - Immunogenicity and safety of pneumococcal vaccination in patients with systemic
      sclerosis.
AB  - Objective: To study the impact of disease and treatment with DMARDs on antibody
      response elicited by either pneumococcal conjugate vaccine (PCV13) or
      pneumococcal polysaccharide vaccine (PPV23) in patients with SSc. Methods: Forty
      four SSc patients and 49 controls received a dose of either PCV13 or PPV23.
      Twelve patients were treated with DMARDs. Antibody levels to pneumococcal
      polysaccharides 6B and 23 F were measured before and 4-6 weeks after vaccination
      using ELISA. Antibody functionality was studied using opsonophagocytic assay
      performed on serotype 23 F. Results: Number of patients, percentage female and
      mean age (years) at vaccination were: 32, 94%, 57.5 years in SSc without DMARDs;
      12, 100%, 55.5 years in SSc on DMARDs and 49, 63% and 50.6 years in controls.
      Post-vaccination antibody levels for both serotypes increased significantly in
      SSc without DMARDs and controls (P < 0.001), but in SSc on DMARDs only for 6B (P
      = 0.041). Compared with the other groups, patients with SSc receiving DMARDs had
      lower post-vaccination antibody levels for both serotypes. Opsonophagocytic assay
      increased significantly in all three groups. No significant difference in
      immunogenicity between PCV13 and PPV23 was seen. Conclusion: Pneumococcal
      vaccination using either PCV13 or PPV23 yielded satisfactory antibody response in
      SSc patients without DMARD treatment, but a lower response in patients treated
      with synthetic DMARDs. Type of pneumococcal vaccine (conjugate or polysaccharide)
      did not significantly influence antibody response. Trial registration:
      ClinicalTrials.gov, http://clinicaltrials.gov, NCT02240888.

PMID- 29325177
TI  - Organization's Effects With Schizoaffective Disorder.

PMID- 29325176
TI  - Dynamic motif occupancy (DynaMO) analysis identifies transcription factors and
      their binding sites driving dynamic biological processes.
AB  - Biological processes are usually associated with genome-wide remodeling of
      transcription driven by transcription factors (TFs). Identifying key TFs and
      their spatiotemporal binding patterns are indispensable to understanding how
      dynamic processes are programmed. However, most methods are designed to predict
      TF binding sites only. We present a computational method, dynamic motif occupancy
      analysis (DynaMO), to infer important TFs and their spatiotemporal binding
      activities in dynamic biological processes using chromatin profiling data from
      multiple biological conditions such as time-course histone modification ChIP-seq
      data. In the first step, DynaMO predicts TF binding sites with a random forests
      approach. Next and uniquely, DynaMO infers dynamic TF binding activities at
      predicted binding sites using their local chromatin profiles from multiple
      biological conditions. Another landmark of DynaMO is to identify key TFs in a
      dynamic process using a clustering and enrichment analysis of dynamic TF binding
      patterns. Application of DynaMO to the yeast ultradian cycle, mouse circadian
      clock and human neural differentiation exhibits its accuracy and versatility. We
      anticipate DynaMO will be generally useful for elucidating transcriptional
      programs in dynamic processes.

PMID- 29325179
TI  - Comprehensive profiles of psychological and social work factors as predictors of
      site-specific and multi-site pain.
AB  - Objective Despite the multifactoriality of work and health, studies of
      psychosocial work factors with pain are typically limited to a few factors. This
      study examined a wide range of factors to determine (i) typical combinations of
      work factor levels ("work situations") and (ii) whether "work situations"
      predicted pain complaints of six anatomic regions. Methods Questionnaires were
      distributed to 6175 employees twice over a two-year period. Latent profile
      analysis was conducted to group employees into profiles of work factor levels.
      Twelve work factors were measured, reflecting six themes: demands, control, role
      expectations, leadership, predictability, and organizational climate. Logistic
      and Poisson regressions compared the groups' risk of pain of the neck, head,
      back, shoulders, legs and arms, as well as multi-site pain (>1 pain site).
      Results Four latent profiles emerged based on relative levels of work factors.
      Profile 1 reflected relatively "desirable" levels of all factors, demonstrating
      the lowest risk of pain. Profile 2 exhibited the highest, and profile 3 the
      lowest levels of both demands and control with similar risks of pain, suggesting
      high levels of control were insufficient to buffer the impact of the combination
      of the other factors. Profile 4 exhibited "undesirable" levels of all factors and
      the highest risk, most notably for multi-site pain [odds ratio (OR) 2.32, 95%
      confidence intervals (CI) 1.80-2.85 compared with profile 1]. Conclusions
      Different compositions of psychosocial exposures were differentially related to
      pain. Future studies should take the complexity of work into account by studying
      comprehensive arrays of co-occurring work factors with health.

PMID- 29325178
TI  - Modulation of O-GlcNAc Levels in the Liver Impacts Acetaminophen-Induced Liver
      Injury by Affecting Protein Adduct Formation and Glutathione Synthesis.
AB  - Overdose of acetaminophen (APAP) results in acute liver failure. We have
      investigated the role of a posttranslational modification of proteins called O
      GlcNAcylation, where the O-GlcNAc transferase (OGT) adds and O-GlcNAcase (OGA)
      removes a single beta-D-N-acetylglucosamine (O-GlcNAc) moiety, in the
      pathogenesis of APAP-induced liver injury. Hepatocyte-specific OGT knockout mice
      (OGT KO), which have reduced O-GlcNAcylation, and wild-type (WT) controls were
      treated with 300 mg/kg APAP and the development of injury was studied over a time
      course from 0 to 24 h. OGT KO mice developed significantly lower liver injury as
      compared with WT mice. Hepatic CYP2E1 activity and glutathione (GSH) depletion
      following APAP treatment were not different between WT and OGT KO mice. However,
      replenishment of GSH and induction of GSH biosynthesis genes were significantly
      faster in the OGT KO mice. Next, male C57BL/6 J mice were treated Thiamet-G
      (TMG), a specific inhibitor of OGA to induce O-GlcNAcylation, 1.5 h after APAP
      administration and the development of liver injury was studied over a time course
      of 0-24 h. TMG-treated mice exhibited significantly higher APAP-induced liver
      injury. Treatment with TMG did not affect hepatic CYP2E1 levels, GSH depletion,
      APAP-protein adducts, and APAP-induced mitochondrial damage. However, GSH
      replenishment and GSH biosynthesis genes were lower in TMG-treated mice after
      APAP overdose. Taken together, these data indicate that induction in cellular O
      GlcNAcylation exacerbates APAP-induced liver injury via dysregulation of hepatic
      GSH replenishment response.

PMID- 29325180
TI  - Sertindole: EEG Analysis, Tolerability, and Clinical Efficacy.
AB  - INTRODUCTION: One of the common side effects of antipsychotic drugs is excessive
      sedation. The treatment with antipsychotics often manifests as an increase in
      slow wave activity in electroencephalography (EEG). The aim of this study was to
      analyze EEG recordings of patients treated with a non-sedative antipsychotic drug
      sertindole with regard to its adverse effects and clinical efficacy. PATIENTS AND
      METHODS: EEG recordings of 45 patients (27 females, mean age 30.1+/-8.7 years)
      with schizophrenia were analyzed. EEG recordings were categorized based on
      abnormalities severity. The clinical efficacy was rated on the Clinical Global
      Impression Scale. RESULTS: Abnormalities from mild to moderate were found in 29%
      of the group. Clinical improvement was observed in 80% of patients.
      Sedation/daytime sleepiness was present in 7% of patients. Other side effects
      were prolongation of QTc (11%, severe 4%), insomnia (9%), extrapyramidal symptoms
      (7%), and heart palpitations (2%). CONCLUSIONS: Patients treated with sertindole
      do not show side effects similar to those found during treatment with other
      antipsychotic drugs. Increased slow wave activity in EEG and sedation were absent
      in the majority of the investigated patients.

PMID- 29325181
TI  - ?

PMID- 29325182
TI  - [Cannabis in Parkinson's Disease: Hype or help?]
AB  - Cannabis buds and extracts as well as synthetic cannabinoids have been available
      on prescription to patients with severe diseases since March 2017, with the costs
      covered by health insurance companies.The prescription of medical marihuana is
      not restricted to specific symptoms and is therefore also valid for patients with
      Parkinson's disease. From a legal perspective, patients who are seriously ill
      even have the right to be treated with cannabis if standard treatment methods are
      unsuccessful or result in unbearable side effects. This also applies even if only
      a slight chance of noticeable improvement is predicted as a result of the
      cannabis treatment.Bearing this in mind and due to an intense media coverage of
      this topic, more and more patients with Parkinson's disease are requesting
      cannabis prescription, which is a challenging situation to their
      neurologists.This article provides an overview of the various cannabis products
      that can be prescribed, the different modes of administration and the available
      literature regarding motor- and non-motor symptoms in Parkinson's disease.
      Furthermore, the authors state their opinion on which indications cannabinoids
      could be useful in treating patients with Parkinson's disease or in which
      situation the patient could or even should be prescribed cannabinoids.
      Additionally, this article presents practical recommendations for the
      prescription of cannabinoids and patient counseling, e. g., on the effects of
      medical marijuana on driving capacity.

PMID- 29325183
TI  - Validation of the Modified Surgeon Periorbital Rating of Edema and Ecchymosis
      (SPREE) Questionnaire: A Prospective Analysis of Facial Plastic and
      Reconstructive Surgery Procedures.
AB  - Although periorbital edema and ecchymosis are commonly encountered after facial
      plastic and reconstructive surgery procedures, there is currently no validated
      grading scale to qualify these findings. In this study, the modified "Surgeon
      Periorbital Rating of Edema and Ecchymosis (SPREE)" questionnaire is used as a
      grading scale for patients undergoing facial plastic surgery procedures. This
      article aims to validate a uniform grading scale for periorbital edema and
      ecchymosis using the modified SPREE questionnaire in the postoperative period.
      This is a prospective study including 82 patients at two different routine
      postoperative visits (second and seventh postoperative days), wherein the staff
      and resident physicians, physician assistants (PAs), patients, and any
      accompanying adults were asked to use the modified SPREE questionnaire to score
      edema and ecchymosis of each eye of the patient who had undergone a plastic
      surgery procedure. Interrater and intrarater agreements were then examined.
      Cohen's kappa coefficient was calculated to measure intrarater and interrater
      agreement between health care professionals (staff physicians and resident
      physicians); staff physicians and PAs; and staff physicians, patients, and
      accompanying adults. Good to excellent agreement was identified between staff
      physicians and resident physicians as well as between staff physicians and PAs.
      There was, however, poor agreement between staff physicians, patients, and
      accompanying adults. In addition, excellent agreement was found for intraobserver
      reliability during same-day visits. The modified SPREE questionnaire is a
      validated grading system for use by health care professionals to reliably rate
      periorbital edema and ecchymosis in the postoperative period. Validation of the
      modified SPREE questionnaire may improve ubiquity in medical literature reporting
      and related outcomes reporting in future.

PMID- 29325184
TI  - [Distal Humerus Fracture in the Elderly].
AB  - Distal humerus fractures show increasing incidence with age. Due to preexisting
      osteoporosis, the surgeon is regularly confronted with complex comminuted
      intraarticular fractures. The maintenance of autonomy in daily life and avoidance
      of permanent care dependency is a dogma in the care of geriatric patients.
      Accordingly, a stable post-operative situation that allows early functional post
      operative treatment is mandatory, especially in the elderly patient. Open
      reduction and stable internal fixation using double plate osteosynthesis are the
      current osteosynthetic standard of treatment. Modern precontoured systems with
      angular stability facilitate stable fixation and reduce surgery time. However,
      complication rates are high, despite the good functional outcomes in the few
      available studies which use modern plate systems in a geriatric patient
      population. Due to the high rate of primary stability, elbow arthroplasty has
      become an established treatment option for complex distal humerus fractures in
      elderly patients. Consequently arthroplasty registry data report a growing number
      of elbow replacements for fracture in recent decades. The standard implant design
      in the fractures in geriatric patients is the cemented "semi-constrained" total
      elbow arthroplasty. The disadvantages of total elbow replacement are the lifelong
      stringent weight restriction patients must adhere to, as well as potential long
      term complications associated with arthroplasty, such as aseptic loosening and
      periprosthetic fractures. Comparative studies with short- and medium-term follow
      up show overall comparable functional results for elbow arthroplasty and double
      plate osteosynthesis, with fewer complications and revisions as well as a shorter
      duration of surgery within the arthroplasty group. However, long-term outcome
      studies are necessary to identify potential long-term complications associated
      with arthroplasty and are pending. Therefore, in reconstruction of fractures of
      the distal humerus which allow stable fixation and early functional post
      operative treatment, open reduction and double plate internal fixation with
      modern locking plate systems remains the gold standard even for geriatric
      patients.

PMID- 29325186
TI  - Qualitative and Quantitative Radiological Measures of Fracture Healing.
AB  - The formulation of appropriate postoperative strategies, following fracture
      repair, currently involves an understanding of radiological and clinical outcome
      measures. This study has evaluated several modalities used to assess the
      progression of bone healing in a sheep tibial segmental defect model. Measures of
      defect optical density and volumetric data including bone density (BD), bone
      volume (BV) and bone mass (BM) were compared with qualitative data involving
      visual appraisal of radiographs [% bridging callus and modified radiographic
      union score tibia (mRUST)] and a clinical outcome measure (locomotory function).
      Percent bridging callus and mRUST measures displayed strong correlation (r =
      0.999), while locomotory function was weakly correlated with bridging callus (r =
      0.029) and mRUST (r = 0.046). There was moderate to strong correlation between
      the qualitative and quantitative data. Bone density, BV and BM showed strong
      correlations within this dataset (BD-BV, r = 0.814; BD-BM, r = 0.818; BV-BM, r =
      1.000). Likewise, optical density measures were strongly correlated with BD (r =
      0.824), BV (r = 0.957) and BM (r = 0.959). The utilization of both qualitative
      and quantitative data, in assessment of the progression of fracture healing, has
      provided valuable insight. Measures of optical density have been shown to make a
      substantial contribution to this assessment and which should be considered for
      use in studies evaluating fracture healing.

PMID- 29325187
TI  - In Vivo Evaluation of Biodegradability and Biocompatibility of Fe30Mn Alloy.
AB  - OBJECTIVES:  This study aims to evaluate the biodegradability and
      biocompatibility of an alloy of iron and manganese (Fe30Mn) in a bone model in
      vivo. METHODS:  Resorption of a Fe30Mn wire was compared with traditional
      permanent 316L stainless steel (SS) wire after bilateral transcondylar femoral
      implantation in 12 rats. Evaluation of biodegradation over 6 months was performed
      using radiography, post-mortem histology and microscopic implant surface
      analysis. RESULTS:  Corrosion and resorption of the novel iron-manganese implant
      with formation of an iron oxide corrosion layer was noted on all post-mortem
      histological sections and macroscopic specimens (corrosion fraction of 0.84 and 0
      for Fe30Mn and 316L SS, respectively). Increased bone ongrowth was observed at
      the wire-bone interface (bone ongrowth fraction of 0.61 and 0.34 for Fe30Mn and
      316L SS, respectively). Occasionally, poorly stained newly formed bone and
      necrotic bone in contact with corrosion was seen. In bone marrow, Fe30Mn alloy
      was scored as a mild local irritant compared with 316L SS (biocompatibility score
      of 8.8 and 5.3, respectively). There was no evidence of systemic adverse
      reaction. CLINICAL SIGNIFICANCE:  Resorbable iron-manganese alloys may offer a
      promising alternative to permanent metallic implants. Further in vivo studies to
      control implant resorption at a rate suitable for fracture healing and to confirm
      the biocompatibility and biosafety of the resorbable Fe30Mn metallic implant are
      necessary prior to use in clinical settings.

PMID- 29325188
TI  - Comparison of Radiographic Measurements of the Femur in Yorkshire Terriers with
      and without Medial Patellar Luxation.
AB  - OBJECTIVE:  This article aimed to compare measurements of anatomical angles of
      the femurs, based on radiography, in Yorkshire Terriers without or with various
      grades of medial patellar luxation (MPL) based on radiography. METHODS:  The
      skeletally mature Yorkshire Terrier dogs without MPL and with various grades of
      MPL were included in this prospective study. Cases with other orthopaedic
      disorders were excluded. For inclusion of the dog, it was required that
      standardized digital radiographs of both femurs in craniocaudal and axial
      directions were available. Measurements of the anatomical lateral proximal
      femoral angle, anatomical lateral distal femoral angle, femoral varus angle,
      anteversion angle and femoral inclination angle were performed. RESULTS:  Forty
      two Yorkshire Terriers (84 hindlimbs) were included in the study. They were
      divided into five groups according to grade of MPL as healthy (n = 12), grade I
      (n = 9), grade II (n = 44), grade III (n = 10) and grade IV (n = 9) dogs. The
      anatomical lateral proximal femoral angle and anteversion angle were
      significantly lower in dogs with grade IV MPL, while anatomical lateral distal
      femoral angle and femoral varus angle were significantly higher. The femoral
      inclination angle values did not differ significantly. CLINICAL SIGNIFICANCE: 
      Yorkshire Terriers affected with grade IV MPL had severe femoral deformities or
      femoral varus and external rotation of the distal femur. Reference range can be
      used as an aid in diagnosis, determining indications and surgical planning for
      corrective osteotomy.

PMID- 29325189
TI  - Comparison of Three Methods to Quantify Laxity in the Canine Hip Joint.
AB  - OBJECTIVES:  Comparison of PennHIP and a novel method to diagnose hip laxity,
      called the Vezzoni modified Badertscher distension device technique. METHODS:  In
      a total of 10 dogs, it was first assessed whether the distraction index (DI) from
      the PennHIP evaluation center could be reproduced by two individual observers. In
      the next two steps, the DI measurements made by the individual observers and the
      PennHIP evaluation center were compared with the laxity index (LI) measured on
      the Vezzoni modified Badertscher distension device view. Finally, the
      interobserver agreement of the DI, LI and Norberg angle was assessed and compared
      with classification criteria. RESULTS:  The results were similar for the first
      three comparisons: there was no evidence for bias, the relation between DI and LI
      was linear and the variability was small. A comparison of the interobserver
      agreement showed that the measurement variability for the NA was substantial,
      while the reproducibility for the DI and LI was equal. CLINICAL SIGNIFICANCE: 
      While the standard ventrodorsal hip extended radiograph is most commonly used for
      diagnosis and screening of canine hip dysplasia, it lacks sensitivity to diagnose
      laxity. To improve the identification of hip joint laxity, distraction-based
      radiographic techniques are helpful. The Vezzoni modified Badertscher distension
      device technique allows for a reliable in-house evaluation of canine hip joint
      laxity.

PMID- 29325190
TI  - Influence of Radiographic Positioning on Canine Sacroiliac and Lumbosacral Angle
      Measurements.
AB  - OBJECTIVES:  To evaluate the influence of radiographic malpositioning on canine
      sacroiliac and lumbosacral inclination angles. METHODS:  Using canine cadavers,
      lateral pelvic radiographs were acquired with the radiographic beam in a neutral
      position and then rotated 5, 10 and 15 degrees  to mimic rotational
      malpositioning. The focal point of the beam was then focused over the abdomen and
      again over mid-diaphysis of the femur to mimic an abdominal or femoral
      radiographic study. RESULTS:  Five degrees of rotational malpositioning did not
      influence measurements of sacroiliac or lumbosacral inclination, but
      malpositioning by more than 5 degrees  led to a significant decrease in both
      sacroiliac and lumbosacral angles. Moving the focal point to the femur
      significantly decreased the measured lumbosacral angle. Abdominally centred
      radiographs had no effect on lumbosacral and sacroiliac angle measurements.
      CLINICAL SIGNIFICANCE:  When evaluating canine lumbosacral and sacroiliac angles
      radiographically, pelvic rotation of more than 5 degrees  should be avoided as
      should the use of lateral radiographs centred over the femur.

PMID- 29325191
TI  - Medium-Term Outcome and CT Assessment of Lateral Foraminotomy at the Lumbosacral
      Junction in Dogs with Degenerative Lumbosacral Stenosis.
AB  - OBJECTIVE:  This article aims to report the medium-term clinical outcome and
      assess persistence of enlargement of the lumbosacral lateral intervertebral
      neurovascular foramen using computed tomography (CT) volumetric analysis in dogs
      following lateral foraminotomy. MATERIALS:  Six dogs that underwent lumbosacral
      lateral foraminotomy on one or both sides were evaluated with CT prior to,
      immediately postoperatively (n = 2) and at 12 to 44 months of follow-up. Five out
      of six dogs had successful clinical outcomes with alleviation of pain and
      increased levels of activity, according to subjective assessment. Immediate
      postoperative CT volumetric analysis of the lateral intervertebral neurovascular
      foramina in two dogs indicated a 650 to 800% increase in volume in extension
      achieved by foraminotomy (four foramens). At subsequent follow-up, bone regrowth
      had occurred with reduction in foraminal volume, though in both dogs foraminal
      volume remained higher than preoperative values. Follow-up CT at a median of 24
      months postoperatively indicated a mean 335% increase in volume of the
      lumbosacral lateral intervertebral neurovascular foramina in extension compared
      with the preoperative foraminal volume. The follow-up volume was substantially
      greater than the presurgical volume in four out of six dogs. CLINICAL
      SIGNIFICANCE:  In this limited case series, lateral foraminotomy achieved
      persistent enlargement of the lumbosacral lateral intervertebral neurovascular
      foramen in the medium term, but osseous regrowth at the site was demonstrated
      which may limit the effectiveness of lateral foraminotomy in the longer term. One
      of two working dogs had recurrent clinical signs that necessitated further
      surgery.

PMID- 29325192
TI  - Single Transsacral Screw and Nut Stabilization of Bilateral Sacroiliac Luxation
      in 20 Cats.
AB  - OBJECTIVE:  This article aims to describe the use of a single transsacral screw
      and nut in a cohort of cats with bilateral sacroiliac (SI) luxation and document
      its radiographic and clinical outcome. METHODS:  Medical records and radiographic
      studies of cats with bilateral SI luxation managed with a transsacral screw and
      nut stabilization were reviewed. Short-term follow-up included clinical
      examination and radiographs. Long-term follow-up was via owner questionnaire.
      RESULTS:  Twenty consecutive cats with bilateral SI luxation were included. Six
      cats (35%) had additional musculoskeletal injuries that required stabilization.
      Luxations were stabilized with a single 2.7 cortical self-tapping transsacral
      screw and nylon nut (a metallic nut was used in one case). Postoperative
      radiographs confirmed SI reduction in all cats and a mean pelvic canal width
      ratio of 1.21 (a ratio of >=1.1 was considered optimal). All cats available at
      follow-up examination were able to walk without signs of discomfort. Evaluation
      of follow-up radiographs showed maintenance of SI reduction and slight reduction
      of mean pelvic canal width ratio (1.18). Fourteen owner questionnaires were
      returned (median follow-up time of 40 months): nine cats were deemed to have
      normal activity and five cats were reported to have slight to mild reduced
      ability to jump or run. CLINICAL SIGNIFICANCE:  The use of transsacral screw and
      nut stabilization of bilateral SI luxation in cats is a successful, repeatable
      and safe technique.

PMID- 29325193
TI  - Stabilization of Olecranon Fractures by Tension Band Wiring or Plate
      Osteosynthesis: A Retrospective Study of 41 Cases.
AB  - OBJECTIVES:  This article aimed to describe olecranon fracture in dogs and cats
      and their stabilization with tension band wiring or plate osteosynthesis, and to
      evaluate complications associated with each technique. METHODS:  Medical records
      of cats and dogs that had been surgically treated for olecranon fractures with
      either tension band wiring or plate osteosynthesis were retrospectively reviewed.
      The surgical technique, complications and long-term outcomes were assessed.
      RESULTS:  Forty-one olecranon fractures were included. Fractures were articular,
      comminuted and open in 90, 31 and 27% of cases, respectively. Tension band wiring
      and plate osteosynthesis were performed in 22 and 19 fractures, respectively.
      Complications occurred more commonly after tension band wiring (74%) compared
      with plate osteosynthesis (27%) (p = 0.002) and these were probably related to it
      being used in comminuted fractures (p = 0.01) or to errors in technique. Minor
      complications included Kirschner wires migration (n = 5), pain (n = 3),
      osteomyelitis (n = 3), skin breakdown (n = 3) and seroma (n = 1). Implant failure
      requiring further fixation (n = 4) was observed only in the tension band wiring
      group. Other major complications included skin wound debridement and closure (n =
      1) and chronic lameness requiring implant removal (n = 7). Long-term functional
      outcomes were excellent regardless of the technique used. CLINICAL SIGNIFICANCE: 
      Plate osteosynthesis should be performed for olecranon fracture repair if
      technically feasible.

PMID- 29325194
TI  - Comparison of Rotation Force to Maintain Acetabular Ventroversion after Double
      Pelvic Osteotomy and 2.5 Pelvic Osteotomy in a Canine Cadaveric Model.
AB  - OBJECTIVE:  The aim of this article was to compare the force required to maintain
      the acetabular ventroversion after double pelvic osteotomy (DPO) and modified
      triple pelvic osteotomy (2.5PO). METHODS:  Unilateral DPO (group A) and
      unilateral modified DPO (group B = 2.5PO) were performed on cadaveric canine
      pelves (n = 10/group). The twisting moment required to maintain fragment position
      for DPO and 2.5DPO was compared. RESULTS:  Mean twisting moment for the DPO group
      [5.92 N/m +/- 2.59 (range, 2.61-12.17 N/m)] and the 2.5PO group [2.11 N/m +/-
      0.93 (range, 0.63 -3.85 N/m)] was significantly different (p < 0.01). CONCLUSION:
      Dorsal cortex osteotomy of the ischium decreases the acetabular segment rotation
      force. Decreased force may facilitate acetabular rotation during DPO procedure.

PMID- 29325195
TI  - Common Calcaneal Tenorrhaphy Revision Using a Central Gastrocnemius Turnover
      Aponeurotic Flap Technique in a Cat.
AB  - A 5-year-old, male castrated, domestic short hair cat was referred to the
      authors' clinic because of wound dehiscence and exposure of tendon stumps after
      tenorrhaphy of the Achilles tendon. Surgical revision was done using an
      aponeurotic flap taken from the proximal stump of the Achilles tendon and sutured
      over the two tendon portions. This technique has been described in humans, but,
      to the authors' knowledge, this has not been reported in cats. Modified type II
      external fixation was used to maintain the tarsocrural joint in extension until
      tendon healing was confirmed ultrasonographically 35 days postoperatively.
      Clinical and ultrasonographic evaluation 60 and 120 days postoperatively showed
      normal limb function and good tendon healing. Long-term follow-up examination 8
      years postoperatively revealed that the cat was in good health with normal gait
      and activity level.

PMID- 29325197
TI  - [From the History of the German Society of Internal Medicine (DGIM) - Part 1: The
      DGIM in the Nazi era].

PMID- 29325196
TI  - Ventral Slot Surgery to Manage Cervical Intervertebral Disc Disease in Three
      Cats.
AB  - OBJECTIVE:  This case series describes the clinical presentation, management and
      outcome of three cats diagnosed with cervical intervertebral disc disease that
      underwent decompressive ventral slot surgery. METHODS:  This is a retrospective
      case series evaluating client-owned cats undergoing a ventral slot surgical
      procedure to manage cervical intervertebral disc disease (n = 3). RESULTS:  A
      routine ventral slot surgery was performed in each case without complication,
      resulting in postoperative neurological improvement in all three cases. CLINICAL
      SIGNIFICANCE:  Ventral slot surgery can be used to achieve effective cervical
      spinal cord decompression with a good long-term outcome in the management of
      feline cervical intervertebral disc herniation. To avoid creating an excessively
      wide slot with the potential for postoperative complications including vertebral
      sinus haemorrhage, vertebral instability or ventral slot collapse, careful
      surgical planning was performed with preoperative measurement of the desired
      maximum slot dimensions.

PMID- 29325198
TI  - [Hygienic Inspections of Ventilation Systems Under Resting Conditions (According
      to DIN 1946-4:1999-03) - A Retrospective Assessment].
AB  - BACKGROUND: Hygienic and microbiologically sterile air quality is essential for
      successful guideline-based work in operating theatres. To ensure clean air and to
      reduce contamination during surgery, ventilation systems are indispensable.
      Ventilation systems should be especially designed to keep the number of particles
      and germs under statutory limits. Therefore, they must be operated to recognised
      standards of good practice and be periodically inspected and maintained. The
      objective of this study was to prove, through the analysis of observation outside
      surgery time (rest condition), the effects of ventilation systems on air quality
      in a medical facility. METHODS: Measurements were taken in 34 operating theatres
      annually over a period of ten years outside surgery time (resting condition) but
      with the air ventilation system operating under full load. 29 operating theatres
      were provided with laminar air flow and five theatres with turbulent air flow
      systems. In each operating theatre, air cleanliness was analysed by measuring the
      amount of airborne particles and airborne germs. Measuring points were determined
      10 mm beneath the supply-air ceiling in the centre of the operating theatre and
      at one position outside the supply-air ceiling. RESULTS: The number of airborne
      particles at the supply-air ceiling was between 0/m3 and 4,441/m3 of air and, as
      such, the limiting factor was never exceeded. However, airborne germ measurements
      of between 0 CFU/m3 and 200 CFU/m3 (CFU: colony forming units) demonstrated that
      the limiting factor for this criterion was exceeded in 10.9% of occasions. In
      general, the values in the middle of the room were higher than at the supply-air
      ceiling. There were significant differences (p < 0.001) between the values at the
      supply-air ceiling, the surgery table and the values outside the supply-air
      ceiling. CONCLUSIONS: The results show the positive impact of ventilation systems
      on the air cleanliness in operating theatres. However, laminar airflow systems
      seem to create cleaner air than conventional ventilation systems. The size of the
      supply-air ceiling plays an important role in the prevention of the contamination
      of the staff, the surgical field, the instrument table and the patient. However,
      the effect on surgical site infections has not been verified. Improved measuring
      methods should be considered.

PMID- 29325199
TI  - [Efficacy and Safety of Indwelling Pleural Catheters].
AB  - In symptomatic malignant pleural effusions, mostly in a palliative situation,
      therapeutic procedures should be chosen to improve dyspnoea and the concomitant
      impairment of quality of life. Indwelling pleural catheters (IPC) have played an
      increasing role in recent years. The efficacy and safety of this method have not
      been adequately clarified under real-life clinical conditions. 94 patients, in
      whom IPC had been implanted because of a clinical indication, were analysed
      retrospectively with respect to efficacy and safety, together with patient
      characteristics, peri- and postinterventional complications, e.g. infections or
      pneumothorax, and long-term follow-up - with special emphasis on the occurrence
      of a pleurodesis. Overall, 89.5% (n = 85) of the patients received an IPC due to
      a recurrent pleural effusion caused by a malignant primary disease. The average
      duration of hospitalisation for patients did not decease as a result of their
      incurable condition and was 3.29 days. In 21.2% (n = 20) of the patients,
      pleurodesis occurred. Method-related complications arose for 33.2% (n = 32) of
      the patients, although further treatment was only needed in 8 patients. Late
      complications developed for 9 of the patients observed. The average survival
      period after implantation was 88.72 days. The results show that IPC is a
      technically straightforward, minimally invasive alternative to recurrent
      punctures or other methods of pleurodesis. A major benefit is the possibility of
      outpatient care.

PMID- 29325200
TI  - Three-Component Domino Knoevenagel/Vinylogous Michael Reaction: Entry to
      Challenging o-Terphenyls.
AB  - An unprecedented organocatalytic three-component domino Knoevenagel/vinylogous
      Michael reaction starting from simple enolizable aldehydes, malononitrile, and
      nitroolefins is reported. This facile two-step domino process provides a
      straightforward stereoselective route to multifunctional vinyl malononitrile
      products (up to 82 % yield, 85:15 d.r.) containing a nitroalkane moiety, and
      contributes to the development of sustainability and atom economy. The
      application of the obtained domino products for synthesis of highly
      functionalized o-terphenyls (of high interest for materials science and medicinal
      chemistry) through subsequent new three-step domino reaction involving
      cyclization-tautomerization-aromatization steps, has been demonstrated.

PMID- 29325201
TI  - Active Intracellular Delivery of a Cas9/sgRNA Complex Using Ultrasound-Propelled
      Nanomotors.
AB  - Direct and rapid intracellular delivery of a functional Cas9/sgRNA complex using
      ultrasound-powered nanomotors is reported. The Cas9/sgRNA complex is loaded onto
      the nanomotor surface through a reversible disulfide linkage. A 5 min ultrasound
      treatment enables the Cas9/sgRNA-loaded nanomotors to directly penetrate through
      the plasma membrane of GFP-expressing B16F10 cells. The Cas9/sgRNA is released
      inside the cells to achieve highly effective GFP gene knockout. The acoustic
      Cas9/sgRNA-loaded nanomotors display more than 80 % GFP knockout within 2 h of
      cell incubation compared to 30 % knockout using static nanowires. More
      impressively, the nanomotors enable highly efficient knockout with just 0.6 nm of
      the Cas9/sgRNA complex. This nanomotor-based intracellular delivery method thus
      offers an attractive route to overcome physiological barriers for intracellular
      delivery of functional proteins and RNAs, thus indicating considerable promise
      for highly efficient therapeutic applications.

PMID- 29325202
TI  - Interfacial Mineral Fusion and Tubule Entanglement as a Means to Harden a Bone
      Augmentation Material.
AB  - A new bone augmenting material is reported, which is formed from calcium-loaded
      hydrogel-based spheres. On immersion of these spheres in a physiological medium,
      they become surrounded with a sheath of precipitate, which ruptures due to a
      build-up in osmotic pressure. This results in the formation of mineral tubes that
      protrude from the sphere surface. When brought into close contact with one
      another, these spheres become fused through the entanglement and subsequent
      interstitial mineralization of the mineral tubules. The tubular calcium phosphate
      induces the expression of osteogenic genes (runt-related transcription factor 2
      (RUNX2), transcription factor SP7 (SP7), collagen type 1 alpha 1 (COL1A1), and
      bone gamma-carboxyglutamic acid-containing protein (BGLAP)) and promotes the
      formation of mineral nodules in preosteoblast cultures comparable to an apatitic
      calcium phosphate phase. Furthermore, alkaline phosphatase (ALP) is significantly
      upregulated in the presence of tubular materials after 10 d in culture compared
      with control groups (p < 0.001) and sintered apatite (p < 0.05). This is the
      first report of a bioceramic material that is formed in its entirety in situ and
      is therefore likely to provide a better proxy for biological mineral than other
      existing synthetic alternatives to bone grafts.

PMID- 29325203
TI  - Fluorescent Diarylethene Photoswitches-A Universal Tool for Super-Resolution
      Microscopy in Nanostructured Materials.
AB  - Super-resolution fluorescence microscopy allows for unprecedented in situ
      visualization of biological structures, but its application to materials science
      has so far been comparatively limited. One of the main reasons is the lack of
      powerful dyes that allow for labeling and photoswitching in materials science
      systems. In this study it is shown that appropriate substitution of diarylethenes
      bearing a fluorescent closed and dark open form paves the way for imaging
      nanostructured materials with three of the most popular super-resolution
      fluorescence microscopy methods that are based on different concepts to achieve
      imaging beyond the diffraction limit of light. The key to obtain optimal
      resolution lies in a proper control over the photochemistry of the photoswitches
      and its adaption to the system to be imaged. It is hoped that the present work
      will provide researchers with a guide to choose the best photoswitch derivative
      for super-resolution microscopy in materials science, just like the correct
      choice of a Swiss Army Knife's tool is essential to fulfill a given task.

PMID- 29325204
TI  - A Transformable Chimeric Peptide for Cell Encapsulation to Overcome Multidrug
      Resistance.
AB  - Multidrug resistance (MDR) remains one of the biggest obstacles in chemotherapy
      of tumor mainly due to P-glycoprotein (P-gp)-mediated drug efflux. Here, a
      transformable chimeric peptide is designed to target and self-assemble on cell
      membrane for encapsulating cells and overcoming tumor MDR. This chimeric peptide
      (C16 -K(TPE)-GGGH-GFLGK-PEG8 , denoted as CTGP) with cathepsin B-responsive and
      cell membrane-targeting abilities can self-assemble into nanomicelles and further
      encapsulate the therapeutic agent doxorubicin (termed as CTGP@DOX). After the
      cleavage of the Gly-Phe-Leu-Gly (GFLG) sequence by pericellular overexpressed
      cathepsin B, CTGP@DOX is dissociated and transformed from spherical nanoparticles
      to nanofibers due to the hydrophilic-hydrophobic conversion and hydrogen bonding
      interactions. Thus obtained nanofibers with cell membrane-targeting 16-carbon
      alkyl chains can adhere firmly to the cell membrane for cell encapsulation and
      restricting DOX efflux. In comparison to free DOX, 45-time higher drug retention
      and 49-fold greater anti-MDR ability of CTGP@DOX to drug-resistant MCF-7R cells
      are achieved. This novel strategy to encapsulate cells and reverse tumor MDR via
      morphology transformation would open a new avenue towards chemotherapy of tumor.

PMID- 29325205
TI  - A Top-Down Strategy toward SnSb In-Plane Nanoconfined 3D N-Doped Porous Graphene
      Composite Microspheres for High Performance Na-Ion Battery Anode.
AB  - Engineering of 3D graphene/metal composites with ultrasmall sized metal and
      robust metal-graphene interfacial interaction for energy storage application is
      still a challenge and rarely reported. In this work, a facile top-down strategy
      is developed for the preparation of SnSb-in-plane nanoconfined 3D N-doped porous
      graphene networks for sodium ion battery anodes, which are composed of several
      tens of interconnected empty N-graphene boxes in-plane firmly embedded with
      ultrasmall SnSb nanocrystals. The all-around encapsulation (plane-to-plane
      contact) architecture that provides a large interface between N-graphene and SnSb
      nanocrystal not only effectively enhances the electron conductivity and
      structural integrity of the overall electrode, but also offers excess interfacial
      sodium storage, thus leading to much enhanced high-rate sodium storage capacity
      and stability, which has been proven by both experimental results and first
      principles simulations. Moreover, this top-down strategy can enable new paths to
      the low-cost and high-yield synthesis of 3D graphene/metal composites for
      applications in energy-related fields and beyond.

PMID- 29325207
TI  - Developing a Journal's Influence Without Impact Factor Madness: Quality in Shape.

PMID- 29325206
TI  - Cyclodextrin-Sandwiched Hexaphyrin Hybrids: Side-to-Side Cavity Coupling Switched
      by a Temperature- and Redox-Responsive Central Device.
AB  - Access to allosteric enzyme mimics that ideally associate communicating
      compartments for catalysis and regulation is still challenging. Whereas a
      sandwich "cavity-catalyst-cavity" approach, developed mainly with cyclodextrins
      and porphyrins, appears promising, its counterpart with hexaphyrins featuring
      rich conformation, aromaticity, and coordination behavior has not been prospected
      at all. We thus developed sandwich hybrids made of two cyclodextrins triply
      linked on each side of a hexaphyrin. The latter displays switchable oxidation
      states with interconvertible conformations (28pi antiaromatic and 26pi aromatic,
      each adopting rectangular and dumbbell forms). These four states are connected by
      two orthogonal switches under redox [aromaticity] and thermal [shape] control.
      This leads to twin compartmentalized confined spaces either locked or unlocked
      depending on the conformation of the hexaphyrin, and the reversibility of the
      lock<->unlock transition relies on the aromaticity of the hexaphyrin. The
      sandwiched heteroannulene thus behaves as an unprecedented dual-responsive double
      latched device. Such hybrid systems open interesting perspectives in the
      allosteric regulation of receptors, catalysts, and machineries.

PMID- 29325208
TI  - Bioinspired Universal Flexible Elastomer-Based Microchannels.
AB  - Flexible and stretchable microscale fluidic devices have a broad range of
      potential applications, ranging from electronic wearable devices for convenient
      digital lifestyle to biomedical devices. However, simple ways to achieve stable
      flexible and stretchable fluidic microchannels with dynamic liquid transport have
      been challenging because every application for elastomeric microchannels is
      restricted by their complex fabrication process and limited material selection.
      Here, a universal strategy for building microfluidic devices that possess
      exceptionally stable and stretching properties is shown. The devices exhibit
      superior mechanical deformability, including high strain (967%) and recovery
      ability, where applications as both strain sensor and pressure-flow regulating
      device are demonstrated. Various microchannels are combined with organic,
      inorganic, and metallic materials as stable composite microfluidics. Furthermore,
      with surface chemical modification these stretchable microfluidic devices can
      also obtain antifouling property to suit for a broad range of industrial and
      biomedical applications.

PMID- 29325209
TI  - Branch-Like Iron Nitride and Carbide Magnetic Fibres Using an Electrospinning
      Technique.
AB  - Fe3 N and Fe3 C nanocomposites have a wide range of applications thanks to their
      ceramic nature, magnetic properties, conductivity and catalytic activity, just to
      cite some. In many fields optimal performances are ensured by crystallinity,
      homogeneity and hierarchical organization. In the present paper, crystalline,
      magnetic and well-defined nanofibres of iron nitride and iron carbide/carbon
      nanocomposite with tunable composition and size were prepared via
      electrospinning. The starting polymeric material was directly electrospun into
      fibres and then calcined, leading to a highly homogeneous final product of
      nanoparticles along the fibres (both outside and inside). A mechanistic study was
      undertaken and here discussed. The magnetic properties of the as-prepared
      nanofibres were also studied. The as-prepared final fibre mat composite material
      can serve as active catalyst, for example, in oxygen reduction reaction (where
      nanofibres outperformed mere nanoparticles), it can serve as functional support
      for classical catalytic processes or, thanks to its magnetic properties, can be
      applied in magnetic-field assisted separation or as magneto-active membranes.

PMID- 29325210
TI  - A New Co-P Nanocomposite with Ultrahigh Relaxivity for In Vivo Magnetic Resonance
      Imaging-Guided Tumor Eradication by Chemo/Photothermal Synergistic Therapy.
AB  - Design of new nanoagents that intrinsically have both diagnostic imaging and
      therapeutic capabilities is highly desirable for personalized medicine. In this
      work, a novel nanotheranostic agent is fabricated based on polydopamine (PDA)
      functionalized Co-P nanocomposites (Co-P@PDA) for magnetic resonance imaging
      (MRI)-guided combined photothermal therapy and chemotherapy. The ultrahigh
      relaxivity of 224.61 mm-1 s-1 can enable Co-P@PDA to be applied as an excellent
      contrast agent for MRI in vitro and in vivo, providing essential and
      comprehensive information for tumor clinical diagnosis. Moreover, Co-P@PDA
      exhibit excellent photothermal performance owing to the strong near-infrared
      (NIR) absorbance of both Co-P nanocomposite and PDA. Highly effective ablation of
      tumors is achieved in a murine tumor model because the NIR laser not only induces
      photothermal effects but also triggers the chemotherapeutic drug on-demand
      release, which endows the Co-P@PDA with high curative effects but little toxicity
      and few side effects. These findings demonstrate that Co-P@PDA are promising
      agents for highly effective and precise antitumor treatment and warrant
      exploration as novel theranostic nanoagents with good potential for future
      clinical translation.

PMID- 29325211
TI  - Uptake and Intracellular Fate of Engineered Nanoparticles in Mammalian Cells:
      Capabilities and Limitations of Transmission Electron Microscopy-Polymer-Based
      Nanoparticles.
AB  - In order to elucidate mechanisms of nanoparticle (NP)-cell interactions, a
      detailed knowledge about membrane-particle interactions, intracellular
      distributions, and nucleus penetration capabilities, etc. becomes indispensable.
      The utilization of NPs as additives in many consumer products, as well as the
      increasing interest of tailor-made nanoobjects as novel therapeutic and
      diagnostic platforms, makes it essential to gain deeper insights about their
      biological effects. Transmission electron microscopy (TEM) represents an
      outstanding method to study the uptake and intracellular fate of NPs, since this
      technique provides a resolution far better than the particle size. Additionally,
      its capability to highlight ultrastructural details of the cellular interior as
      well as membrane features is unmatched by other approaches. Here, a summary is
      provided on studies utilizing TEM to investigate the uptake and mode-of-action of
      tailor-made polymer nanoparticles in mammalian cells. For this purpose, the
      capabilities as well as limitations of TEM investigations are discussed to
      provide a detailed overview on uptake studies of common nanoparticle systems
      supported by TEM investigations. Furthermore, methodologies that can, in
      particular, address low-contrast materials in electron microscopy, i.e.,
      polymeric and polymer-modified nanoparticles, are highlighted.

PMID- 29325212
TI  - Enhancing Molecular n-Type Doping of Donor-Acceptor Copolymers by Tailoring Side
      Chains.
AB  - In this contribution, for the first time, the molecular n-doping of a donor
      acceptor (D-A) copolymer achieving 200-fold enhancement of electrical
      conductivity by rationally tailoring the side chains without changing its D-A
      backbone is successfully improved. Instead of the traditional alkyl side chains
      for poly{[N,N'-bis(2-octyldodecyl)-naphthalene-1,4,5,8-bis(dicarboximide)-2,6
      diyl](NDI)-alt-5,5'-(2,2'-bithiophene)} (N2200), polar triethylene glycol type
      side chains is utilized and a high electrical conductivity of 0.17 S cm-1 after
      doping with (4-(1,3-dimethyl-2,3-dihydro-1H-benzoimidazol-2
      yl)phenyl)dimethylamine is achieved, which is the highest reported value for n
      type D-A copolymers. Coarse-grained molecular dynamics simulations indicate that
      the polar side chains can significantly reduce the clustering of dopant molecules
      and favor the dispersion of the dopant in the host matrix as compared to the
      traditional alkyl side chains. Accordingly, intimate contact between the host and
      dopant molecules in the NDI-based copolymer with polar side chains facilitates
      molecular doping with increased doping efficiency and electrical conductivity.
      For the first time, a heterogeneous thermoelectric transport model for such a
      material is proposed, that is the percolation of charge carriers from conducting
      ordered regions through poorly conductive disordered regions, which provides
      pointers for further increase in the themoelectric properties of n-type D-A
      copolymers.

PMID- 29325213
TI  - A New Colorimetric Platform for Protein Detection Based on Recognition-Induced
      Cascade of Polymeric Nanoparticles Disassembly.
AB  - Despite great progress, it is still of high interest to explore new homogeneous
      assays for simple, visual, and selective protein detection. Herein, one new
      colorimetric sensor has been developed for visual detection of protein by using
      polymeric micelles as a sensing scaffold and the molecular recognition between
      protein and the ligand on the surface of the polymeric micelles as the driving
      force to trigger the readout of the detection signal. The polymeric micelles
      formed via the self-assembly of the amphiphilic block polymer biotin-labeled
      poly(ethylene glycol)-block-poly(3-acryl aminophenylboronic acid) are endowed
      with colorful feature by incorporation of alizarin red S (ARS) into the
      hydrophobic core. Based on the response to streptavidin recognition, these
      micelles are further disintegrated through the competitive binding of alpha
      cyclodextrin with boronic acid for disassociation of ARS, which achieves orange
      yellow to pink-purple transition in 2 h. This work will open the way to develop
      one new mix-and-measure, visual, and homogeneous assay.

PMID- 29325214
TI  - A spike in mechanotransductive adenosine triphosphate release from red blood
      cells in microfluidic constrictions only occurs with rare donors.
AB  - OBJECTIVE: Wan et al (Proc Natl Acad Sci USA, 105, 2008, 16432) demonstrated that
      RBCs rapidly and transiently release a spike of 300% more ATP shortly downstream
      from a short microfluidic constriction where the cells experience a sudden
      increase in shear stress. More recent work by Cinar et al (Proc Natl Acad Sci
      USA, 112, 2015, 11783), however, yielded no evidence for a similar spike in ATP
      release downstream of the constriction. Our aim was to determine whether a
      transient spike in mechanotransduction is the typical response of RBCs to the
      sudden onset of increased shear. METHODS: We investigate ATP release downstream
      of a microfluidic constriction for 15 participants using a luciferase-based
      photoluminescent assay. RESULTS: While we observe mechanotransductive ATP release
      from blood drawn from all donors, we find evidence of a spike in ATP
      concentration after the microfluidic constriction for only 2 of 15 participants.
      No clear trends in ATP release are found with respect to the magnitude of the
      applied shear stress, or to the gender, age, or physical activity (Baecke) index
      of the donor. CONCLUSIONS: In aggregate, all data acquired to date suggest that a
      spike in mechanotransductive ATP due to a suddenly applied increase in shear
      stress occurs in blood drawn from only 14% of the population.

PMID- 29325215
TI  - Oplopane Sesquiterpenes from Ligularia knorringiana and Their Anti-Complementary
      Activity.
AB  - Three new oplopane sesquiterpenes, knorringianalarins D - F (1 - 3,
      respectively), and five known analogues (4 - 8, respectively), were isolated from
      the roots and rhizomes of Ligularia knorringiana. The structures of three new
      compounds were identified as 4-acetoxy-11alpha,12-epoxy-2beta-hydroxy-3beta-(2
      methylbutyryloxy)-9alpha-(4-methylsenecioyloxy)oplop-10(14)-ene (1), 3beta,4
      diacetoxy-9alpha-(4-acetoxy-4-methylsenecioyloxy)-11alpha,12-epoxy-8alpha-(2
      methylbutyryloxy)oplop-10(14)-ene (2), and (1R,5R,6R,7R,9R)-5,9,11-trihydroxy
      4,15-dinoroplop-10(14)-en-3-one (3) based on spectroscopic methods including 1D-
      and 2D-NMR, mass spectrometry, and CD spectroscopy techniques. All compounds were
      evaluated for their anti-complementary activity on the classical pathway of the
      complement system in vitro. Among which, three oplopane sesquiterpenes (3, 7, and
      8) exhibited better anti-complementary effects with CH50 values ranging from 0.33
      to 0.89 mm, which are plausible candidates for developing potent anti
      complementary agents.

PMID- 29325217
TI  - Neutrophil infiltration to the brain is platelet-dependent, and is reversed by
      blockade of platelet GPIbalpha.
AB  - Neutrophils are key components of the innate immune response, providing host
      defence against infection and being recruited to non-microbial injury sites.
      Platelets act as a trigger for neutrophil extravasation to inflammatory sites but
      mechanisms and tissue-specific aspects of these interactions are currently
      unclear. Here, we use bacterial endotoxin in mice to trigger an innate
      inflammatory response in different tissues and measure neutrophil invasion with
      or without platelet reduction. We show that platelets are essential for
      neutrophil infiltration to the brain, peritoneum and skin. Neutrophil numbers do
      not rise above basal levels in the peritoneum and skin and are decreased (~60%)
      in the brain when platelet numbers are reduced. In contrast neutrophil
      infiltration in the lung is unaffected by platelet reduction, up-regulation of
      CXCL-1 (2.4-fold) and CCL5 (1.4-fold) acting as a compensatory mechanism in
      platelet-reduced mice during lung inflammation. In brain inflammation targeting
      platelet receptor GPIbalpha results in a significant decrease (44%) in platelet
      mediated neutrophil invasion, while maintaining platelet numbers in the
      circulation. These results suggest that therapeutic blockade of platelet
      GPIbalpha could limit the harmful effects of excessive inflammation while
      minimizing haemorrhagic complications of platelet reduction in the brain. The
      data also demonstrate the ability to target damaging brain inflammation in stroke
      and related disorders without compromising lung immunity and hence risk of
      pneumonia, a major complication post stroke. In summary, our data reveal an
      important role for platelets in neutrophil infiltration to various tissues,
      including the brain, and so implicate platelets as a key, targetable component of
      cerebrovascular inflammatory disease or injury.

PMID- 29325216
TI  - Obstetrical providers' preferred mode of delivery and attitude towards non
      medically indicated caesarean sections: a cross-sectional study.
AB  - OBJECTIVE: To describe obstetrical providers' delivery preferences and attitudes
      towards caesarean section without medical indication, including on maternal
      request, and to examine the association between provider characteristics and
      preferences/attitudes. DESIGN: Cross-sectional study. SETTING: Two public and two
      private hospitals in Argentina. POPULATION: Obstetrician-gynaecologists and
      midwives who provide prenatal care and/or labour/delivery services. METHODS:
      Providers in hospitals with at least 1000 births per year completed a self
      administered, anonymous survey. MAIN OUTCOME MEASURES: Provider delivery
      preference for low-risk women, perception of women's preferred delivery method,
      support for a woman's right to choose her delivery method and willingness to
      perform caesarean section on maternal request. RESULTS: 168 providers
      participated (89.8% coverage rate). Providers (93.2%) preferred a vaginal
      delivery for their patients in the absence of a medical indication for caesarean
      section. Whereas 74.4% of providers supported their patient's right to choose a
      delivery method in the absence of a medical indication for caesarean section and
      66.7% would perform a caesarean section upon maternal request, only 30.4% would
      consider a non-medically indicated caesarean section for their own personal
      delivery or that of their partner. In multivariate adjusted analysis, providers
      in the private sector [odds ratio (OR) 4.70, 95% CI 1.19-18.62] and obstetrician
      gynaecologists (OR 4.37, 95% CI 1.58-12.09) were more willing than either
      providers working in the public/both settings or midwives to perform a caesarean
      section on maternal request. CONCLUSIONS: Despite the ethical debate surrounding
      non-medically indicated caesarean sections, we observe very high levels of
      support, especially by providers in the private sector and obstetrician
      gynaecologists, as aligned with the high caesarean section rates in Argentina.
      TWEETABLE ABSTRACT: Non-medically indicated c-section? 74% of sampled Argentine
      OB providers support women's right to choose.

PMID- 29325218
TI  - EQUAL Candida Score: An ECMM score derived from current guidelines to measure
      QUAlity of Clinical Candidaemia Management.
AB  - Candida species frequently cause blood stream infections and are reported to be
      the third to tenth most commonly isolated pathogens. Guidelines and standardised
      treatment algorithms provided by professional organisations aim to facilitate
      decision-making regarding diagnosis, management and treatment of candidaemia. In
      routine clinical practise, however, it may be challenging to comply with these
      guidelines. The reasons include lack of familiarity or feasibility to adherence,
      but also their length and complexity. There is no tool to measure guideline
      adherence currently. To provide such a tool, we reviewed the current guidelines
      provided by the European Society for Clinical Microbiology and Infectious
      Diseases (ESCMID) and by the Infectious Diseases Society of America (IDSA), and
      selected the strongest recommendations for management quality as the bases for
      our scoring tool. Factors incorporated were diagnostic (blood cultures,
      echocardiography, ophthalmoscopy, species identification) and follow-up
      procedures (repeat blood cultures until negative result) as well as key treatment
      parameters (echinocandin treatment, step down to fluconazole depending on
      susceptibility result, CVC removal). The EQUAL Candida Score weighs and
      aggregates factors recommended for the ideal management of candidaemia and
      provides a tool for antifungal stewardship as well as for measuring guideline
      adherence.

PMID- 29325219
TI  - Molecular basis of the flavin-based electron-bifurcating caffeyl-CoA reductase
      reaction.
AB  - Flavin-based electron bifurcation (FBEB) is a recently discovered mode of energy
      coupling in anaerobic microorganisms. The electron-bifurcating caffeyl-CoA
      reductase (CarCDE) catalyzes the reduction of caffeyl-CoA and ferredoxin by
      oxidizing NADH. The 3.5 A structure of the heterododecameric Car(CDE)4 complex of
      Acetobacterium woodii, presented here, reveals compared to other electron
      transferring flavoprotein/acyl dehydrogenase family members an additional
      ferredoxin-like domain with two [4Fe-4S] clusters N-terminally fused to CarE. It
      might serve, in vivo, as specific adaptor for the physiological electron
      acceptor. Kinetic analysis of a CarCDE(?Fd) complex indicates the bypassing of
      the ferredoxin-like domain by artificial electron acceptors. Site-directed
      mutagenesis studies substantiated the crucial role of the C-terminal arm of CarD
      and of ArgE203, hydrogen-bonded to the bifurcating FAD, for FBEB.

PMID- 29325220
TI  - Profile, risk factors and outcome of acute kidney injury in paediatric acute-on
      chronic liver failure.
AB  - BACKGROUND & AIMS: There are no studies on acute kidney injury in paediatric
      acute-on-chronic liver failure. This study was planned with aim to describe the
      clinical presentation and outcome of acute kidney injury among paediatric acute
      on-chronic liver failure patients. METHODS: Data of all children 1-18 years of
      age presenting with acute chronic liver failure (Asia pacific association for the
      study of the liver definition) was reviewed. Acute kidney injury was defined as
      per Kidney Diseases-Improving Global Outcomes guidelines. Poor outcome was
      defined as death or need for liver transplant within 3 months of development of
      acute kidney injury. RESULTS: A total of 84 children with acute-on-chronic liver
      failure were presented to us in the study period. Acute kidney injury developed
      in 22.6% of patients with acute-on-chronic liver failure. The median duration
      from acute-on-chronic liver failure to development of acute kidney injury was 4
      weeks (Range: 2-10 weeks). The causes of acute kidney injury were hepatorenal
      syndrome (31.6%), sepsis (31.6%), nephrotoxic drugs (21%), dehydration (10.5%)
      and bile pigment related acute tubular necrosis in one patient. On univariate
      analysis, higher baseline bilirubin, higher international normalized ratio,
      higher paediatric end stage liver disease, presence of systemic inflammatory
      response syndrome and presence of spontaneous bacterial peritonitis had
      significant association with presence of acute kidney injury. On logistic
      regression analysis, presence of systemic inflammatory response syndrome
      (adjusted OR: 8.659, 95% CI: 2.18-34.37, P = .002) and higher baseline bilirubin
      (adjusted OR: 1.07, 95% CI: 1.008-1.135, P = .025) were independently associated
      with presence of acute kidney injury. Of the patients with acute kidney injury,
      5(26.3%) survived with native liver, 10(52.6%) died and 4 (21.1%) underwent liver
      transplantation. CONCLUSION: Acute kidney injury developed in 22.6% of children
      with acute-on-chronic liver failure. Bilirubin more than 17.7 mg/dL and presence
      of systemic inflammatory response syndrome were high risk factors for acute
      kidney injury. Development of acute kidney injury in a child with acute-on
      chronic liver failure suggests poor outcome and need for early intervention.

PMID- 29325221
TI  - Naphthalene Derivatives and Quinones from Ventilago denticulata and Their Nitric
      Oxide Radical Scavenging, Antioxidant, Cytotoxic, Antibacterial, and
      Phosphodiesterase Inhibitory Activities.
AB  - New naphthalene derivatives (1 and 2) and a new isomer (3) of ventilagolin,
      together with known anthraquinones, chrysophanol (4), physcion or emodin 3-methyl
      ether (5), and emodin (6), were isolated from vines of Ventilago denticulata. The
      isolated compounds exhibited cytotoxic activity with IC50 values of 1.15 - 40.54
      MUg/ml. Compounds 1 - 3 selectively exhibited weak antibacterial activity (MIC
      values of 200.0 - 400.0 MUg/ml), while emodin (6) displayed moderate
      antibacterial activity with MIC value of 25.0 MUg/ml. The isolated compounds
      showed nitric oxide and DPPH radical scavenging activities. Compounds 1 - 3 and 6
      exhibited weak xanthine oxidase inhibitory activity, while emodin (6) acted as an
      aromatase inhibitor with the IC50 value of 10.1 MUm. Compounds 1 and 2 exhibited
      phosphodiesterase 5 inhibitory activity with IC50 values of 8.28 MUm and 6.48
      MUm, respectively.

PMID- 29325222
TI  - Pneumonia as a cardiovascular disease.
AB  - Community-acquired pneumonia (CAP) is an important cause of death around the
      globe. Up to 30% of patients admitted to hospital for CAP develop cardiovascular
      complications (i.e. new/worsening heart failure, new/worsening arrhythmias,
      myocardial infarctions and/or strokes), acutely and up to 10 years thereafter.
      Cardiac complications result from complex interactions between preexisting
      conditions, relative ischaemia, upregulation of the sympathetic system, systemic
      inflammation and direct pathogen-mediated damage to the cardiovascular system.
      The exact mechanisms underlying the direct host-pathogen interactions are of
      great interest to identify potential therapeutic and preventative targets for
      CAP. In this review, we summarize the epidemiological data, risk factors and the
      pathogen-driven cardiovascular damage affecting patients with CAP.

PMID- 29325223
TI  - Maternal thyroid hormone insufficiency during pregnancy and risk of
      neurodevelopmental disorders in offspring: A systematic review and meta-analysis.
AB  - BACKGROUND: In the last 2 decades, several studies have examined the association
      between maternal thyroid hormone insufficiency during pregnancy and
      neurodevelopmental disorders in children and shown conflicting results. AIM: This
      systematic review aimed to assess the evidence for an association between
      maternal thyroid hormone insufficiency during pregnancy and neurodevelopmental
      disorders in children. We also sought to assess whether levothyroxine treatment
      for maternal thyroid hormone insufficiency improves child neurodevelopment
      outcomes. METHODS: We performed systematic literature searches in MEDLINE,
      EMBASE, PSYCinfo, CINAHL, AMED, BNI, Cochrane, Scopus, Web of Science, GreyLit,
      Grey Source and Open Grey (latest search: March 2017). We also conducted targeted
      web searching and performed forwards and backwards citation chasing. Meta
      analyses of eligible studies were carried out using the random-effects model.
      RESULTS: We identified 39 eligible articles (37 observational studies and 2
      randomized controlled trials [RCT]). Meta-analysis showed that maternal
      subclinical hypothyroidism and hypothyroxinaemia are associated with indicators
      of intellectual disability in offspring (odds ratio [OR] 2.14, 95% confidence
      interval [CI] 1.20 to 3.83, P = .01, and OR 1.63, 95% CI 1.03 to 2.56, P = .04,
      respectively). Maternal subclinical hypothyroidism and hypothyroxinaemia were not
      associated with attention deficit hyperactivity disorder, and their effect on the
      risk of autism in offspring was unclear. Meta-analysis of RCTs showed no evidence
      that levothyroxine treatment for maternal hypothyroxinaemia or subclinical
      hypothyroidism reduces the incidence of low intelligence quotient in offspring.
      LIMITATIONS: Although studies were generally of good quality, there was evidence
      of heterogeneity between the included observational studies (I2 72%-79%).
      CONCLUSION: Maternal hypothyroxinaemia and subclinical hypothyroidism may be
      associated with intellectual disability in offspring. Currently, there is no
      evidence that levothyroxine treatment, when initiated 8- to 20-week gestation
      (mostly between 12 and 17 weeks), for mild maternal thyroid hormone insufficiency
      during pregnancy reduces intellectual disability in offspring.

PMID- 29325224
TI  - Hereditary kidney cancer syndromes: Genetic disorders driven by alterations in
      metabolism and epigenome regulation.
AB  - Although hereditary kidney cancer syndrome accounts for approximately five
      percent of all kidney cancers, the mechanistic insight into tumor development in
      these rare conditions has provided the foundation for the development of
      molecular targeting agents currently used for sporadic kidney cancer. In the late
      1980s, the comprehensive study for hereditary kidney cancer syndrome was launched
      in the National Cancer Institute, USA and the first kidney cancer-associated
      gene, VHL, was identified through kindred analysis of von Hippel-Lindau (VHL)
      syndrome in 1993. Subsequent molecular studies on VHL function have elucidated
      that the VHL protein is a component of E3 ubiquitin ligase complex for hypoxia
      inducible factor (HIF), which provided the basis for the development of tyrosine
      kinase inhibitors targeting the HIF-VEGF/PDGF pathway. Recent whole-exome
      sequencing analysis of sporadic kidney cancer exhibited the recurrent mutations
      in chromatin remodeling genes and the later study has revealed that several
      chromatin remodeling genes are altered in kidney cancer kindred at the germline
      level. To date, more than 10 hereditary kidney cancer syndromes together with
      each responsible gene have been characterized and most of the causative genes for
      these genetic disorders are associated with either metabolism or epigenome
      regulation. In this review article, we describe the molecular mechanisms of how
      an alteration of each kidney cancer-associated gene leads to renal tumorigenesis
      as well as denote therapeutic targets elicited by studies on hereditary kidney
      cancer.

PMID- 29325225
TI  - Influence of CYP2D6, CYP3A4, CYP3A5 and ABCB1 Polymorphisms on Pharmacokinetics
      and Safety of Aripiprazole in Healthy Volunteers.
AB  - The aim of this study was to investigate the effect of polymorphisms in
      cytochrome P450 (CYP) 2D6, CYP3A4 and CYP3A5 enzymes and in P-glycoprotein (P-gp)
      on the pharmacokinetics and safety of aripiprazole and, its active metabolite,
      dehydro-aripiprazole, in 148 healthy volunteers from six bioequivalence trials
      receiving a single oral dose of aripiprazole. The plasma concentrations of both
      analytes were measured by LC-MS/MS. CYP2D6 (*3,*4,*5,*6,*7,*9 and copy number
      variations), CYP3A4 (*20 and *22), CYP3A5*3 and C3435T, C1236T and G2677T/A in
      ABCB1 gene were determined. As the number of active CYP2D6 alleles decreased,
      AUC0-t , Cmax and t1/2 of aripiprazole were higher and clearance of aripiprazole,
      AUC0-t of dehydro-aripiprazole and ratio dehydro-aripiprazole/aripiprazole were
      lower. AUC0-t of aripiprazole of poor metabolizer (PM) subjects was increased by
      50% compared to extensive metabolizers (EM), and AUC0-t of dehydro-aripiprazole
      was decreased by 33%. ABCB1 1236TT subjects had a lower clearance of aripiprazole
      (p = 0.023) and AUC0-t (p = 0.039) and Cmax of dehydro-aripiprazole (p = 0.036)
      compared to C/C. CYP3A5*3/*3 subjects had a 10% lower ratio dehydro
      aripiprazole/aripiprazole than *1/*3 (p = 0.019). Adverse drug reactions (ADRs)
      had a directly proportional relationship with AUC0-t of aripiprazole (p = 0.001),
      especially nausea/vomiting, which were more common in women (p = 0.005). Women
      and CYP3A5*1/*1 subjects showed more often dizziness (p = 0.034; p = 0.009).
      Pharmacokinetics of aripiprazole is affected by CYP2D6 phenotype but also by sex
      and C1236T (ABCB1 gene), while dehydro-aripiprazole pharmacokinetics is affected
      by CYP2D6 and C1236T. The ratio dehydro-aripiprazole/aripiprazole was influenced
      by CYP2D6 phenotype and CYP3A5*3. Concentrations of aripiprazole, sex, CYP3A5*3
      and CYP2D6 were involved in the development of ADRs.

PMID- 29325226
TI  - Citrullinated histone H3, a biomarker of neutrophil extracellular trap formation,
      predicts the risk of venous thromboembolism in cancer patients.
AB  - : Essentials Neutrophil extracellular traps (NETs) might play a role in cancer
      related coagulopathy. We determined NET biomarkers and followed cancer patients
      for venous thromboembolism (VTE). We found a constant association with VTE for
      citrullinated histone H3. Biomarkers of NET formation could reflect a novel
      pathomechanism of cancer-related VTE. SUMMARY: Background Neutrophil
      extracellular traps (NETs) are decondensed chromatin fibers that might play a
      role in the prothrombotic state of cancer patients. Objectives To investigate
      whether the levels of citrullinated histone H3 (H3Cit), a biomarker for NET
      formation, cell-free DNA (cfDNA) and nucleosomes predict venous thromboembolism
      (VTE) in cancer patients. Patients/Methods Nine-hundred and forty-six patients
      with newly diagnosed cancer or progression after remission were enrolled in this
      prospective observational cohort study. H3Cit, cfDNA and nucleosome levels were
      determined at study inclusion, and patients were followed for 2 years. VTE
      occurred in 89 patients; the cumulative 3-month, 6-month, 12-month and 24-month
      incidence rates of VTE were 3.7%, 6.0%, 8.1%, and 10.0%, respectively. Results
      Patients with elevated H3Cit levels (> 75th percentile of its distribution, n =
      236) experienced a higher cumulative incidence of VTE (2-year risk of 14.5%) than
      patients with levels below this cut-off (2-year risk of 8.5%, n = 710). In a
      competing-risk regression analysis, a 100 ng mL-1 increase in H3Cit level was
      associated with a 13% relative increase in VTE risk (subdistribution hazard ratio
      [SHR] 1.13, 95% confidence interval [CI] 1.04-1.22). This association remained
      after adjustment for high VTE risk and very high VTE risk tumor sites, D-dimer
      level, and soluble P-selectin level (SHR 1.13, 95% CI 1.04-1.22). The association
      of elevated nucleosome and cfDNA levels with VTE risk was time-dependent, with
      associations with a higher risk of VTE only during the first 3-6 months.
      Conclusion These data suggest that biomarkers of NET formation are associated
      with the occurrence of VTE in cancer patients, indicating a role of NETs in the
      pathogenesis of cancer-associated thrombosis.

PMID- 29325227
TI  - Soluble ST2 in end-stage heart failure, before and after support with a left
      ventricular assist device.
AB  - BACKGROUND: The interleukin-33 (IL-33)/suppressor of tumorigenicity 2 (ST2)
      pathway is suggested to play an important role in fibrosis, remodelling and the
      progression of heart failure (HF). Increased soluble (sST2) levels are associated
      with adverse outcome in the average HF population. Less is known about sST2
      levels in end-stage HF. Therefore, we studied sST2 levels in end-stage HF and the
      effect of unloading by left ventricular assist device (LVAD) support on sST2
      levels. METHOD AND RESULTS: Serial plasma measurements of sST2 were performed pre
      implantation and 1, 3 and 6 months after (LVAD) implantation in 38 patients. sST2
      levels were elevated in end-stage HF just prior to LVAD implantation (74.2 ng/mL
      [IQR 54.7-116.9]; normal <35 ng/mL) and decreased substantially during LVAD
      support, to 29.5 ng/mL [IQR 24.7-46.6](P < .001). Patients with INTERMACS profile
      I had significantly higher sST2 levels compared to patients in profile II and
      profile III. A moderate correlation was found between sST2 and C-reactive protein
      (r = .580, P < .010). CONCLUSION: Levels of sST2 are elevated in end-stage HF
      patients with variability that suggests multiple inputs to a pro-inflammatory and
      pro-fibrotic pathway. Cardiogenic shock and increased C-reactive protein levels
      are associated with higher sST2 levels. LVAD support results in a significant
      drop in sST2 levels with normalization within 3 months postimplantation. This
      suggests that LVAD support leads to lessening of fibrosis and inflammation, which
      might eventually be used to target medical policy: explantation of the LVAD
      versus permanent use or cardiac transplantation.

PMID- 29325229
TI  - Dual Drug Targeting of Mutant Bcr-Abl Induces Inactive Conformation: New Strategy
      for the Treatment of Chronic Myeloid Leukemia and Overcoming Monotherapy
      Resistance.
AB  - Bcr-Abl is an oncogenic fusion protein which expression enhances tumorigenesis,
      and has been highly associated with chronic myeloid leukemia (CML). Acquired drug
      resistance in mutant Bcr-Abl has enhanced pathogenesis with the use of single
      therapy agents such as nilotinib. Moreover, allosteric targeting has been
      identified to consequentially inhibit Bcr-Abl activity, which led to the recent
      development of ABL-001 (asciminib) that selectively binds the myristoyl pocket.
      Experimental studies have revealed that the combination of nilotinib and ABL-001
      induced a 'bent' conformation in the C-terminal helix of Bcr-Abl; a benchmark of
      inhibition, thereby exhibiting a greater potency in the treatment of CML,
      surmounting the setbacks of drug resistance, disease regression and relapse.
      Therefore, we report the first account of the dynamics and conformational
      analysis of oncogenic T334I Bcr-Abl by dual targeting. Our findings revealed that
      unlike in the Bcr-Abl-Nilotinib complex, dual targeting by both inhibitors
      induced the bent conformation in the C-terminal helix that varied with time. This
      was coupled with significant alteration in Bcr-Abl stability, flexibility, and
      compactness and an overall structural re-orientation inwards towards the
      hydrophobic core, which reduced the solvent-exposed residues indicative of
      protein folding. This study will facilitate allosteric targeting and the design
      of more potent allosteric inhibitors for resistive target proteins in cancer.

PMID- 29325228
TI  - Effects of trastuzumab and afatinib on kinase activity in gastric cancer cell
      lines.
AB  - The molecular mechanism of action of the HER2-targeted antibody trastuzumab is
      only partially understood, and the direct effects of trastuzumab on the gastric
      cancer signaling network are unknown. In this study, we compared the molecular
      effect of trastuzumab and the HER kinase inhibitor afatinib on the receptor
      tyrosine kinase (RTK) network and the downstream-acting intracellular kinases in
      gastric cancer cell lines. The molecular effects of trastuzumab and afatinib on
      the phosphorylation of 49 RTKs and 43 intracellular kinase phosphorylation sites
      were investigated in three gastric cancer cell lines (NCI-N87, MKN1, and MKN7)
      using proteome profiling. To evaluate these effects, data were analyzed using
      mixed models and clustering. Moreover, proliferation assays were performed. Our
      comprehensive quantitative analysis of kinase activity in gastric cancer cell
      lines indicates that trastuzumab and afatinib selectively influenced the HER
      family RTKs. The effects of trastuzumab differed between cell lines, depending on
      the presence of activated HER2. The effects of trastuzumab monotherapy were not
      transduced to the intracellular kinase network. Afatinib alone or in combination
      with trastuzumab influenced HER kinases in all cell lines; that is, the effects
      of monotherapy and combination therapy were transduced to the intracellular
      kinase network. These results were confirmed by proliferation analysis.
      Additionally, the MET-amplified cell line Hs746T was identified as afatinib
      nonresponder. The dependence of the effect of trastuzumab on the presence of
      activated HER2 might explain the clinical nonresponse of some patients who are
      routinely tested for HER2 expression and gene amplification in the clinic but not
      for HER2 activation. The consistent effects of afatinib on HER RTKs and
      downstream kinase activation suggest that afatinib might be an effective
      candidate in the future treatment of patients with gastric cancer irrespective of
      the presence of activated HER2. However, MET amplification should be taken into
      account as potential resistance factor.

PMID- 29325231
TI  - Accuracy of FDG PET-CT response assessment following radiotherapy alone for head
      and neck squamous cell carcinoma: Retrospective analysis of 45 patients.

PMID- 29325230
TI  - Protocadherin-8 promotes invasion and metastasis via laminin subunit gamma2 in
      gastric cancer.
AB  - Growing evidence suggests that protocadherins (PCDH) play crucial roles in
      pathogenesis and progression of cancers, including gastric cancer (GC).
      Protocadherin-8 (PCDH8) was previously reported to be involved in metastasis of
      GC, but functional studies yielded inconsistent results and the molecular
      mechanism remained unknown. The present study aimed to explore the clinical
      relevance, function and molecular mechanism of PCDH8 in GC. Data from the GEPIA
      and Kaplan-Meier plotter databases showed that high expression of PCDH8 was
      significantly correlated with poorer prognosis in GC. Ectopic expression of PCDH8
      in GC cells promoted invasion and migration in vitro and metastasis in vivo, and
      knockdown of PCDH8 inhibited invasion and migration in vitro. RNA sequencing
      followed by gene set enrichment analysis found a remarkable enrichment in the
      extracellular matrix receptor interaction pathway, with the expression of laminin
      subunit gamma2 (LAMC2) being significantly increased in the PCDH8-overexpressing
      group. High expression of LAMC2 was significantly correlated to poor prognosis in
      GC in GEPIA database. Upregulation of LAMC2 following PCDH8 overexpression was
      further confirmed by immunohistochemistry in liver metastatic lesions of nude
      mice. To our knowledge, this is the first report of the metastasis-enhancing
      property and molecular mechanism through upregulation of LAMC2 of PCDH8 in
      cancer. High expression of PCDH8 could be used as a biomarker for poor prognosis
      in clinical practice.

PMID- 29325232
TI  - Expression of CD163 in hereditary gingival fibromatosis: A possible association
      with TGF-beta1.
AB  - BACKGROUND: Although several studies have discussed some of the molecular and
      cellular changes associated with hereditary gingival fibromatosis (HGF), its
      pathogenesis is still largely unclear. This study was directed to detect and
      outline the degree of relationship between the immunophenotyped macrophages (M2)
      expressing CD163 and TGF-beta1 in patients with gingival overgrowth due to HGF.
      METHODS: Biopsies from 20 patients suffering from HGF and 20 normal control
      subjects were harvested, histologically and immunohistochemically stained then,
      analyzed and statistically compared and correlated for CD163 immunoexpression and
      TGF-beta1. RESULTS: All HGF specimens expressed TGF-beta1 by most of the
      connective tissue fibroblasts, with statistically high significant mean of area %
      (2.61 +/- 0.41) compared to normal controls (0.11 +/- 0.06; P = .001). All
      control specimens revealed negligible CD163 immunostaining of the few
      inflammatory cells found with a mean area of % (0.69 +/- 0.12), while the
      specimens of HGF cases showed statistically significant higher CD163 expression
      (3.39 +/- 0.75) at (P = .007). A statistically significant higher mean % of M2
      cells expressing CD163 in relation to the total number of the inflammatory cells
      was revealed in HGF (34.46 +/- 2.04) compared to the control group (16.36 +/-
      2.39; P-value <= .05). Moderate correlation between CD163 and TGF-beta1 was
      detected in HGF (r = .451; P-value < .05). CONCLUSIONS: CD163 and TGF-beta1 were
      clearly expressed in HGF cases compared to healthy control patients, with
      significant correlation. In HGF, the increase in CD 163-positive cells was
      specific and not dependent on the chronic gingival inflammation.

PMID- 29325233
TI  - Catatonia: An Approach to Diagnosis and Treatment.

PMID- 29325234
TI  - Prospective Associations Between Infant Sleep at 12 Months and Autism Spectrum
      Disorder Screening Scores at 24 Months in a Community-Based Birth Cohort.
AB  - BACKGROUND: Sleep problems have been associated with autism spectrum disorder
      (ASD) symptoms and diagnosis. However, past research has studied the simultaneous
      association of sleep problems with precursor ASD symptoms. Using data from a
      birth cohort, we estimate prospective associations between infant sleep
      characteristics at 12 months and later ASD screening scores at 24 months.
      METHODS: We obtained data from children (N = 1,096) and their mothers as
      participants in the Conditions Affecting Neurocognitive Development and Learning
      in Early Childhood longitudinal birth cohort study. Mothers were enrolled between
      2006 and 2011, when they were 16-26 weeks pregnant. Using linear regression, we
      examined the influence of infant sleep characteristics (nighttime and daytime
      sleep, night wakings, and sleep onset latency) at 12 months on ASD screening
      scores at 24 months while controlling for other psychosocial characteristics.
      RESULTS: The number of night wakings was the only sleep characteristic at 12
      months to be significantly associated with the development of early ASD symptoms
      at 24 months (B = 0.097, P = .021; 95% CI, 0.014 to 0.180). However, other
      competing risks, especially child socioemotional competence at 12 months (B =
      0.573, P < .001; 95% CI, 0.361 to 0.785), showed stronger relative contributions
      in predicting ASD risk. CONCLUSIONS: Infants with more sleep problems by 12
      months, especially those waking more often during the night, showed an increased
      number of early ASD symptoms a year later. This study suggests that infant sleep
      characteristics could constitute one clinical sign of ASD risk, together with key
      psychosocial characteristics.

PMID- 29325235
TI  - Taking on the Role of Editor in Chief.

PMID- 29325236
TI  - Treatment With a Ghrelin Agonist in Outpatient Women With Anorexia Nervosa: A
      Randomized Clinical Trial.
AB  - OBJECTIVE: To assess the effects of relamorelin-an agonist of the appetite
      stimulating hormone ghrelin, which has effects on gastric emptying-on (1) weight
      gain and (2) gastric emptying in women with anorexia nervosa. METHODS: In a
      randomized, double-blind, placebo-controlled design, the effects of the ghrelin
      agonist relamorelin were studied in 22 outpatient women with anorexia nervosa,
      diagnosed using DSM-5 criteria. The study was conducted at the Massachusetts
      General Hospital Clinical Research Center between March 11, 2013, and February
      26, 2015. Ten participants were randomly assigned to relamorelin 100 MUg
      subcutaneously daily (mean +/- SEM age: 28.9 +/- 2.4 y), and 12 were randomly
      assigned to placebo (28.9 +/- 1.9 y). We measured changes in weight and gastric
      emptying time using a gastric emptying breath test (GEBT) for relamorelin versus
      placebo after 4 weeks of treatment. RESULTS: At baseline, subjects did not differ
      in weight, plasma ghrelin levels, or gastric emptying time. Three subjects
      randomized to relamorelin stopped use of the study medication due to reported
      feelings of increased hunger. After 4 weeks, there was a trend toward an increase
      in weight in participants randomized to relamorelin (mean +/- SEM change: 0.86 +/
      0.40 kg) compared to placebo (0.04 +/- 0.28 kg; P = .07), and gastric emptying
      time was significantly shorter in patients taking relamorelin (median
      [interquartile range]: 58.0 [51.0, 78.0] minutes) compared to placebo (85.0
      [75.8,100.5] minutes; P = .03). CONCLUSIONS: Treatment with a ghrelin agonist in
      women with anorexia nervosa significantly decreases gastric emptying time, leads
      to a trend in weight gain after only 4 weeks, and is well-tolerated. Further
      study is necessary to determine the long-term safety and efficacy of a ghrelin
      agonist in the treatment of anorexia nervosa. TRIAL REGISTRATION:
      ClinicalTrials.gov identifier: NCT01642550.

PMID- 29325237
TI  - Neuroleptic Malignant Syndrome: Diagnosis and Management.
AB  - Objective: To provide an overview of neuroleptic malignant syndrome (NMS) for the
      general practitioner with the most up-to-date information on etiology, workup,
      and management. Data Sources: The search using PubMed included articles with the
      key words neuroleptic malignant syndrome, antipsychotics, neuroleptics,
      diagnosis, and treatment of neuroleptic malignant syndrome published in English
      from January 2000 to 2017. Single-case reports and articles dealing with the
      pediatric patient population were excluded. Study Selection: Over 4,000 articles
      met the search criteria. After eliminating single-case reports, pediatric cases,
      reports in pregnant patients, and duplicates, 87 articles underwent screening.
      Forty-two articles were included in this review. Results: The literature is rich
      with cases of NMS associated with the use of neuroleptics and various medications
      with neuroleptic-like effects. Questions remain with regard to pathophysiology
      and optimal treatment. NMS is a rare but potentially lethal consequence of the
      use of antipsychotic medications that requires familiarity with the condition in
      order to rapidly recognize its onset and appropriately intervene. Conclusions:
      NMS mortality rates have declined over the past 30 years, most likely due to
      early recognition of the syndrome and appropriate intervention. Nonetheless,
      clinicians, especially primary care clinicians who are using this class of drugs
      more often for adjunctive treatments, must be cognizant of this syndrome and the
      implications of their use..

PMID- 29325239
TI  - Insomnia and Psychopathological Features Associated With Restless Legs Syndrome
      in Chinese Adolescents.
AB  - OBJECTIVE: Little is known about psychopathological features associated with
      restless legs syndrome (RLS) in pediatric populations. This study examined sleep
      duration, insomnia, and psychopathological profile associated with RLS in a large
      community sample of adolescents. Methods: Participants included 11,831
      adolescents from 3 counties of Shandong, China. Mean age of the participants was
      15.0 (SD = 1.5) years, and 51% were boys. In November and December 2015,
      participants completed a structured questionnaire to assess sleep duration, sleep
      problems, behavioral/emotional problems, and hopelessness. RLS was assessed by
      the 2003 National Institutes of Health (NIH) Restless Legs Syndrome Diagnosis and
      Epidemiology Workshop criteria. RESULTS: Of the sample, 9.5% met the 2003 NIH
      workshop criteria for RLS, and 2.2% had RLS at least 3 times per week. Compared
      with adolescents without RLS, adolescents with RLS < 3 times per week and those
      with RLS >= 3 times per week demonstrated significantly higher rates of insomnia
      symptoms (13.8%, 20.0%, and 36.4%, respectively; chi2 = 117.84, P < .0001),
      internalizing (9.1%, 18.5%, and 34.1%; chi2 = 238.84, P < .001) and externalizing
      (9.8%, 17.4%, and 34.1%; chi2 = 193.87, P < .001) problems, and hopelessness
      (13.0%, 16.9%, and 27.8%; chi2 = 54.10, P < .001). After adjusting for
      demographics and internalizing and externalizing problems, RLS >= 3 times per
      week was associated with a doubled risk of insomnia (OR = 2.05; 95% CI, 1.53
      2.75). After adjusting for demographics, sleep duration, and insomnia, RLS >= 3
      times per week was associated with a more than doubled risk of internalizing (OR
      = 2.65; 95% CI, 1.94-3.62) and externalizing problems (OR = 2.75; 95% CI, 2.02
      3.74). CONCLUSIONS: RLS is associated with increased risk of insomnia,
      hopelessness, and both internalizing and externalizing problems. Our findings
      suggest that clinicians need to assess RLS in adolescents with sleep and mental
      health problems.

PMID- 29325240
TI  - Advanced Topics in Major Depressive Disorder: Practical Strategies to Improve
      Remission.
AB  - Most patients with major depressive disorder will not achieve remission with
      initial treatment. Strategies to increase the likelihood of achieving remission
      include regularly measuring response, assessing adverse effects and adherence,
      addressing non-mood symptoms, and knowing when to switch or augment
      antidepressants. In this CME Health Spectrum activity, follow 2 patient cases
      that illustrate these topics.

PMID- 29325238
TI  - Psychometrics of the Self-Report Concise Associated Symptoms Tracking Scale (CAST
      SR): Results From the STRIDE (CTN-0037) Study.
AB  - OBJECTIVE: The self-report Concise Associated Symptoms Tracking Scale (CAST-SR)
      was developed to track mania, irritability, anxiety, panic, and insomnia symptoms
      among depressed outpatients receiving antidepressant medication. Given the
      overlap between these domains, depression, and stimulant use disorders, we
      reexamined CAST-SR psychometrics in a novel sample: individuals with stimulant
      use disorder receiving aerobic exercise or health education interventions.
      METHODS: Using the subsample of stimulant-dependent (following DSM-IV criteria)
      individuals prescribed antidepressants (N = 124) from the multisite Stimulant
      Reduction Intervention Using Dosed Exercise (CTN-0037) trial (total sample N =
      302), conducted July 2010 to February 2013, we analyzed CAST-SR data collected at
      the first assessment after participant's discharge from residential treatment. We
      also evaluated the convergent/discriminant validity of the CAST-SR with several
      self-report questionnaires. RESULTS: Confirmatory factor analysis revealed a 12
      item measure composed of 4 factors: irritability, anxiety, panic, and insomnia.
      This factor structure loaded only in participants prescribed antidepressant
      medication, not in those who were not prescribed antidepressants. These results
      replicate the original CAST-SR factor structure, except for the mania factor,
      which failed to load. Internal consistency was high (alpha = 0.92 for total scale
      and alpha = 0.78-0.89 for the 4 factors), and convergent validity was
      established, especially for the insomnia and irritability factors, alongside the
      total score with depressive symptoms, insomnia, quality of life, suicide risk,
      and physical health measures. CONCLUSIONS: These results demonstrate the factor
      structure, reliability, and validity of the CAST-SR in a novel population of only
      individuals with stimulant use disorders receiving both exercise/health education
      interventions and antidepressant medication. TRIAL REGISTRATION:
      ClinicalTrials.gov identifier: NCT01141608.

PMID- 29325242
TI  - [Keep pace with the time, do our best in pathology].

PMID- 29325243
TI  - [Comments on the 2017 update version of the consensus on pathologic diagnosis of
      gastrointestinal stromal tumor].

PMID- 29325241
TI  - Typical lesions in the fetal nervous system: correlations between fetal magnetic
      resonance imaging and obstetric ultrasonography findings.
AB  - Central nervous system (CNS) malformations play a role in all fetal
      malformations. Ultrasonography (US) is the best screening method for identifying
      fetal CNS malformations. A good echographic study depends on several factors,
      such as positioning, fetal mobility and growth, the volume of amniotic fluid, the
      position of the placenta, the maternal wall, the quality of the apparatus, and
      the sonographer's experience. Although US is the modality of choice for routine
      prenatal follow-up because of its low cost, wide availability, safety, good
      sensitivity, and real-time capability, magnetic resonance imaging (MRI) is
      promising for the morphological evaluation of fetuses that otherwise would not be
      appropriately evaluated using US. The aim of this article is to present
      correlations of fetal MRI findings with US findings for the major CNS
      malformations.

PMID- 29325244
TI  - [Expert consensus on pathologic diagnosis of melanoma in China].

PMID- 29325245
TI  - [Clinical characteristics of high-grade B-cell lymphomas with rearrangement of
      MYC, bcl-6 and bcl-2].
AB  - Objective: To investigate the clinicopathologic features of patients with high
      grade B-cell lymphomas (HGBL) that have rearrangements of MYC, bcl-6 and bcl-2.
      Methods: One hundred and fifty-eight B-cell lymphomas patients from Institute of
      Hematology and Blood Diseases Hospital from January 2016 to April 2017 were
      detected by fluorescence in situ hybridization (FISH) with double color split
      apart probes. Results: Among 158 B-cell lymphomas, 3 cases with MYC, bcl-2 and
      bcl-6 rearrangements were identified, 1 of which also had CCND1/IgH
      translocation. All three patients were of older age, with poor prognostic
      parameters, multiple organs involvements, elevated LDH and advanced-tumor stage.
      Two of the three patients were treated with high-intensity chemotherapy and had
      no remission with an overall survival of 9 months and 11 months respectively. One
      patient had follow-up with no treatment. Histologically, all three cases showed a
      spectrum of morphologic features. Although initially categorized as lymphoblastic
      lymphoma, diffuse large lymphoma and mantle cell lymphoma respectively, two cases
      were associated with germinal center B-cell (GCB) immunophenotype and 1 case with
      non-GCB immunophenotype. They had a high proliferation index as assessed by
      immunostaining for Ki-67 (60%-90%). Conclusions: MYC(+) bcl-2(+) bcl-6(+) HGBL is
      an aggressive disease with multiple organ involvement, high serum LDH levels,
      advanced stage disease, poor prognosis and shorter patient survival. The
      diagnosis should be made by histopathology combined with FISH analysis. Its
      separation from other types of B cell large cell lymphoma is of clinical
      importance.

PMID- 29325246
TI  - [Diagnostic significance of lymph node core needle biopsy for lymphoproliferative
      disease: a clinicopathologic study of 1 013 cases].
AB  - Objective: To study the clinicopathologic features of lymphoproliferative disease
      by lymph node core needle biopsy(CNB)and to evaluate the diagnostic significance
      of CNB for lymphoproliferative disease. Methods: The annual distribution, entity
      constitute, clinical finding, gross feature, morphologic change, affiliate study
      and repeat biopsy diagnosis of 1 013 cases of lymph node CNB diagnosed at West
      China Hospital of Sichuan University from January 2009 to December 2015 were
      investigated. Results: (1) Proportion of lymph node CNB in total amount of biopsy
      specimens increased from 0.2% in 2009 to 0.8% in 2015.(2) The study cohort
      included 471 lymphomas, 12 atypical lymphoid hyperplasia (ALH), 136 suspected
      lymphomas, 372 benign lesions, and 22 cases of descriptive diagnoses. The most
      common types were diffuse large B cell lymphoma and T-lymphoblastic lymphoma. (3)
      Majority of patients were adolescents and children younger than 20 years or the
      elderly older than 60 years. 53.1% CNB tumor specimen consisted of >=4 tissue
      cores and 40.5% were >2 cm in length. (4) 104 CNB cases with previous history of
      excision biopsy was included 45 carcinomas(no metastatic carcinoma was found), 32
      lymphomas for treatment observation.1/14 suspicious lymphomas, 1/1 ALH and 3/22
      cases benign lesions were diagnosed as lymphoma by repeat biopsy respectively.
      (5) 217 CNB cases were diagnosed as lymphoma by subsequent CNB (70), or
      subsequent excision biopsy (147) including 78.5%(73/93) suspected lymphomas, 5/7
      ALH and 32.3%(20/62)benign lesions. Conclusions: Lymph node CNB has certain
      clinical indications, although limited for the diagnosis of lymphoproliferative
      disorders. Suspected lymphomas and ALH diagnosed by CNB should be followed by
      repeat tissue biopsy. For the benign lesions by CNB it does not rule out
      additional biopsy to further investigate the lesion.

PMID- 29325247
TI  - [Impact of PRDM1 gene inactivation on C-MYC regulation in diffuse large B-cell
      lymphoma].
AB  - Objective: To investigate the role of PRDM1 gene inactivaion in the regulation of
      C-MYC in diffuse large B-cell lymphoma (DLBCL), and to explore the correlation of
      its immunophenotype and prognosis. Methods: 100 cases paraffin-embedded DLBCL
      tissues were collected from January 2009 to December 2015 at the First Affiliated
      Hospital of Xinjiang Medical University along with 20 cases of reactive
      proliferative lymph nodes as control. Immunohistochemical methods were used to
      detect the expression of CD20, CD10, MUM1, Ki-67, bcl-6, PRDM1/Blimp1, C-MYC and
      PAX5 protein. The tumors were classified into two subtypes according to Hans
      classification.The expression of PRDM1 and C-MYC gene in tumor group and control
      group was detected by reverse transcription PCR (RT-PCR) and the relationship
      between PRDM1 and C-MYC gene was analyzed.OCI-LY1 (GCB subtype) and OCI-LY3 (non
      GCB subtype) cell lines were transfected with small interfering RNA by cationic
      liposome reagent transfection, and the expression of C-MYC in the transfected
      cell lines was detected by RT-PCR and Western blot. The Kaplan-Meier method was
      used to analyze the prognostic significance of PRDM1/Blimp1 and C-MYC at protein
      and mRNA levels. Results: There were 27 cases of GCB subtype and 73 cases of non
      GCB subtype according to Hans classification. The positive expression of Blimp1
      in DLBCL group and proliferative lymph nodes in control group was seen in
      26(26.0%) and 20 cases(100%), respectively. There were 58 cases with high
      expression of PRDM1 at mRNA level, including 22 cases of GCB subtype and 36 cases
      non-GCB subtype, and the difference was statistically significant (P=0.004).
      There were differences in PRDM1 gene expression between the two immunological
      subtypes, serum lactate dehydrogenase (serum LDH) level, presence of B symptoms,
      tumor primary sites and other clinical pathological parameters, while C-MYC
      expression was different in gender, IPI score, and serum LDH levels. Upon
      PRDM1/Blimp1 gene silencing in the two cell lines, C-MYC protein and gene
      expression were up-regulated in the transfection group, compared with the blank
      control group and negative control group by reverse transcription PCR and Western
      blot analyses. Moreover, PRDM1 expression was significantly associated with C
      MYC(chi(2)=7.648, P=0.006) at mRNA level. Conclusion: The up-regulation of C-MYC
      gene expression induced by PRDM1 inactivation in DLBCL may play an important role
      for the development of DLBCL.PRDM1 protein and mRNA are associated with
      immunophenotyping and PRDM1 mRNA is a marker of poor prognosis.

PMID- 29325248
TI  - [Survival of patients with primary central nervous system diffuse large B-cell
      lymphoma: impact of gene aberrations and protein overexpression of bcl-2 and C
      MYC, and selection of chemotherapy regimens].
AB  - Objective: To investigate the impact of clinicopathological features, gene
      rearrangements and protein expression of bcl-6, bcl-2, C-MYC and chemotherapy
      regime on the prognosis of patients with primary central nervous system diffuse
      large B-cell lymphoma (PCNS-DLBCL). Methods: Thirty-three cases of PCNS-DLBCL
      diagnosed from January 2006 to December 2016 at Zhejiang Cancer Hospital were
      collected. The expression of CD10, bcl-6, bcl-2, MUM1 and MYC were detected by
      immunohistochemical staining (IHC). The presence of EB virus was detected by in
      situ hybridization(EBER). Copy number variation (ICN) and translocation status of
      bcl-6, bcl-2 and C-MYC genes were detected by fluorescence in situ hybridization
      (FISH). The relationship between the above indexes and the prognosis was analyzed
      by univariate, bivariate survival analysis and multiple Cox hazard regression
      analysis. Results: The study included 33 patients of PCNS-DLBCL, without evidence
      of primary or secondary immunodeficient disease. Male to female ratio was
      1.36?1.00, and the average age was 56 years. Twenty cases had single lesion while
      13 had multiple lesions. Deep brain involvement was seen in 12 cases. All
      patients underwent partial or total tumor resection. Five patients received whole
      brain post-surgery radiotherapy, nine patients received high-dose methotrexate
      (HD-MTX) based chemotherapy, and 12 patients received whole-brain radiotherapy
      combined with HD-MTX based chemotherapy. Severn patients received no further
      treatment and rituximab was used in 8 patients. According to the Hans model, 27
      cases were classified as non-GCB subtypes (81.8%). Bcl-2 was positive in 25 cases
      (75.8%, 25/33) and highly expressed in 8 (24.2%). MYC was positive in 12 cases
      (36.4%) and double expression of bcl-2 and MYC was seen in 6 cases. EBER positive
      rate was 10.0%(3/30), all of which had multiple lesions. Two bcl-6 gene
      translocations and 3 amplifications were found in 28 patients. Two
      translocations, 3 ICN or with both bcl-2 gene translocation and ICN were found in
      30 patients. Four ICNs of C-MYC gene were found in 28 patients. Elevated protein
      in cerebrospinal fluid (CSF) was found in 13 patients. LDH increased in 10 cases.
      Follow-up period was 2-90 months with the average survival time of (23.0+/-3.7)
      months and two-year survival rate of 39.0%. Univariate survival analysis showed
      that overexpression of bcl-2 protein (>=70%) and MYC protein (>=40%), bcl-2 gene
      abnormality (including copy number increase and translocation), C-MYC gene copy
      number increased were adverse factors for survival. C-MYC/ bcl-2 gene double hit
      was seen in 2 cases. Bivariate survival analysis found that of bcl-2/MYC protein
      double expression and bcl-2 and C-MYC genes double aberration were significantly
      associated with adverse outcomes. Cox multivariate risk regression analysis found
      that gender, cerebrospinal fluid protein increasing, and ICN of C-MYC gene were
      independent poor prognostic factors. DH-MTX based comprehensive chemotherapy was
      associated with better prognosis. Conclusions: Double hit at genomic level (copy
      number variations and gene rearrangements) and double protein expression of bcl-2
      and C-MYC in PCNS-DLBCL are significantly associated with an adverse outcome. DH
      MTX based comprehensive treatment may prolong the patient survival.

PMID- 29325249
TI  - [Clinicopathologic features of primary hepatic marginal zone lymphoma of mucosa
      associated lymphoid tissue and hepatic pseudolymphoma].
AB  - Objective: To study the clinicopathological features of primary hepatic
      extranodal marginal zone lymphoma of mucosa associated lymphoid tissue (MALT
      lymphoma) and hepatic pseudolymphoma, and to discuss their differential
      diagnosis, treatment and prognosis. Methods: Three primary hepatic MALT lymphomas
      and two hepatic pseudolymphomas collected from January 2012 to March 2017 in the
      First Affiliated Hospital of Nanjing Medical University were evaluated by HE and
      immunohistochemistry(IHC), in-situ hybridization and immunoglobulin (Ig) gene
      rearrangement detection, and the relevant literature reviewed. Results: In the
      three MALT lymphomas, tumor cells infiltrated the portal areas with nodular
      pattern, and invaded the surrounding normal liver with serpiginous configuration
      and formation of confluent sheets. A number of bile ducts were entrapped within
      the lesions, and showed lymphoepithelial lesion. Reactive lymphoid follicles were
      present and surrounded by tumor cells, consisting of predominantly centrocyte
      like cells and monocytoid B cells. There were clusters of epithelioid histiocytes
      in one case. The tumor cells were positive for CD20, PAX5 and negative for CD5,
      CD23, CD10, bcl-6, and cyclin D1. In the two hepatic pseudolymphomas, the lesions
      presented as solitary nodules well-demarcated from the surrounding liver tissue;
      one case was partially encapsulated with fibrous tissue. Entrapped bile ducts
      were only found at the edge of the lesions without lymphoepithelial lesion. The
      lesions comprised of massive lymphoid proliferation consisting predominantly of
      reactive lymphoid follicles, but not monocytoid B-cells or atypical cells. By
      IHC, a mixture of B- and T-cell population was identified. A monoclonal
      rearrangement of the Ig gene was detected in all three MALT lymphomas but not in
      two pseudolymphomas. Interphase fluorescence in situ hybridiazation test for
      MALT1 break-apart gene was positive in two cases of MALT lymphomas and EBER was
      negative in all studied cases. Conclusions: Primary heptic MALT lymphoma and
      pseudolymphoma are both rare lymphoid proliferative lesions of liver. These two
      lesions have overlapping histological and IHC features and are top differential
      diagnosis to each other. A combination analysis of morphology, immunophenotype
      and Ig gene rearrangement is helpful to distinguish between them.

PMID- 29325250
TI  - [Myofibroma/myofibromatosis: a clinicopathologic analysis of 9 cases].
AB  - Objective: To investigate the clinical and histological features, diagnosis and
      differential diagnosis of myofibroma/myofibromatosis. Methods: The clinical data
      and pathology features of nine cases of myofibroma/myofibromatosis were collected
      from August 2011 to November 2016 in Affiliated Drum Tower Hospital, Nanjing
      University Medical School and Children's Hospital of Nanjing Medical University.
      Immunohistochemistry(IHC), PDGFRB molecular analysis and ETV6-NTRK3 gene fusion
      were performed and relevant literature reviewed. Results: There were 7 males and
      2 females, with age ranging from 3 days to 18 years (mean 5 years). The tumors
      were located in head and neck (eight cases) and trunk (one case). Clinically, the
      tumors presented as freely movable nodules. Microscopically, they appeared
      biphasic with alternating light- and dark-staining areas. The light-staining area
      consisted mainly of plump myoid spindle cells with eosinophilic cytoplasm
      arranged in nodules, short fascicles, or whorls.The dark-staining area was
      composed of round or polygonal cells with slightly hyperchromatic nuclei or small
      spindle cells arranged around a distinct hemangiopericytoma-like vascular
      pattern. IHC showed the tumor cells in the light-staining area were strongly
      positive for vimentin and SMA, while cells in dark-staining area were strongly
      positive for vimentin, and weakly for SMA. Tumor cells were negative for desmin,
      S-100 protein, h-Caldesmon, CD34 and STAT6. Analysis of PDGFRB mutations was
      performed in seven cases. Two cases showed 12 exon point mutation c. 1681
      c>T(p.R561C), one case showed 14 exon point mutation c. 1998C>G (p.N666K). ETV6
      NTRK3 gene fusion was not detected by fluorescence in situ hybridization in four
      patients under three years old. All cases were followed for 6 to 68 months, with
      two recurrences. Conclusions: Myofibroma/myofibromatosis is an uncommon benign
      myofibroblastic tumor of infancy and childhood. The tumor can appear biphasic,
      and may show PDGFRB point mutation which is of potential diagnostic value.

PMID- 29325252
TI  - [Clinicopathologic analysis and classification of 2 093 cases of lymphomas:
      experiences in Heilongjiang Province of China].

PMID- 29325251
TI  - [Extrapleural solitary fibrous tumor with uncommon histology: a clinicopathologic
      analysis of 7 cases].
AB  - Objective: To investigate the clinicopathologic characteristics,
      immunophenotypes, and differential diagnostic features of extra-pleural solitary
      fibrous tumor (SFT) with uncommon histology. Methods: Seven cases of extra
      pleural SFT with uncommon histology were collected during January 2015 and
      December 2016 in Zhejiang Provincal People's Hospital; the clinical and
      radiologic features, histomorphology, immunophenotype and prognosis were
      analyzed. EnVision method was used for immunohistochemical staining of STAT6,
      CD34 and other differential diagnosis associated markers. Results: There were
      five male and two female patients, age from 23 to 54 years (mean=39 years). Three
      tumors were located in the soft tissue of head and neck, two in trunk
      subcutaneous soft tissue, one in sella region, and one in the kidney. Grossly the
      tumors ranged from 0.4 to 8.0 cm (mean=3.1 cm). Microscopically, all three head
      and neck cases resembled giant cell angiofibroma/giant cell subtype SFT, and one
      case showed sheet-like pattern of the multinucleated syncytial cells, creating a
      biphasic arrangement similar to myofibroma. Both truncal tumor resembled
      lipomatous type SFT, with one similar to dermatofibrosarcoma protuberans and the
      other to atypical spindle cell lipomatous tumor. The sella tumor showed
      morphology of a conventional SFT with high grade sarcomatous transformation. The
      renal tumor demonstrated a malignant SFT with entrapped benign renal tubules,
      mimicking a biphase synovial sarcoma or a malignant mixed epithelial and stromal
      tumor. By immunohistochemistry, all seven SFTs showed diffuse and strong nuclear
      reactivity to antibody against STAT6. Conclusions: Extra-pleural SFTs show a
      significant heterogeneity of morphology and biological behavior which could cause
      differential confusion.Careful attention to its characteristic histomorphology
      with the use of STAT6 immunohistochemistry can help distinguish this tumor from
      its many mimickers.

PMID- 29325253
TI  - [Expression of PD-L1 and clinicopathologic correlation in invasive ductal
      carcinoma of breast with nodal metastasis].

PMID- 29325254
TI  - [Hemangioma arising in subependymal giant cell astrocytoma: report of a case].

PMID- 29325255
TI  - [Mullerian-type clear cell adenocarcinoma in male: report of a case].

PMID- 29325256
TI  - [Cervical spinal cord hemangioblastome: report of a case].

PMID- 29325257
TI  - [Sinus hemangioma of mesosalpinx mimicking angiosacoma on frozen sections: report
      of a case].

PMID- 29325258
TI  - [Ichthyosis uteri: report of a case].

PMID- 29325259
TI  - [Research and application of multisite fluorescence in-situ hybridization in
      diagnosis of cutaneous melanoma].

PMID- 29325260
TI  - [Research progress of NDRG1 in molecular mechanism of tumor invasion and
      metastasis].

PMID- 29325261
TI  - [Consensus for diagnosis and treatment of uterine myoma].

PMID- 29325262
TI  - [Strengthen the management of pregnancy, decrease the stillbirth incidence of
      China].

PMID- 29325263
TI  - [Analysis of 2 204 stillbirths in 11 hospitals of Guangdong province].
AB  - Objective: To analyze the incidence and causes of stillbirth in 11 hospitals of
      Guangdong province, and to explore the appropriate interventions. Methods:
      Clinical data of stillbirth in 11 hospitals of Guangdong province were collected
      from January 2014 to December 2016. The gestational weeks, causes, maternal
      conditions and other factors were analyzed. Results: (1) From 2014 to 2016, 103
      472 newborns were delivered in the 11 hospitals, and the number of stillbirth was
      2 204, with the incidence of 2.13%. Among them, 0.71%(738/103 472) was
      therapeutic induction, 1.42%(1 066/103 472) was natural stillbirth. At different
      gestational age (<28 weeks, 28-<37 weeks and >=37 weeks), the incidence of
      stillbirth was 55.63% (1 226/2 204), 28.45% (627/2 204) and 15.92% (351/2 204),
      respectively, with statistically significant difference (P<0.01). (2) For
      stillbirth<28 weeks, the first reason was therapeutic induction, accounting for
      53.34% (654/1 226). For stillbirth during 28-37 weeks, pre-eclampsia was the
      major cause, accounting for 40.67% (255/627). And for full-term stillbirth, the
      causes were umbilical cord factors (19.37%, 68/351), abnormal labor (17.09%,
      60/351). (3) In all the stillbirth cases, the incidence of fetal growth
      restriction (FGR) <28 weeks was significantly higher than that during 28-37 weeks
      [23.49% (288/1 226) vs 18.02% (113/627) , P<0.01]. (4) The stillbirth rate during
      labor was significantly higher in women >=35 years old than in younger women
      [63.88% (191/299) vs 36.12% (108/299) ; chi(2)=9.346, P=0.000]. For the causes of
      stillbirth during labor, the incidence of severe maternal obstetrical
      complications [61.11% (33/54) vs 38.89% (21/54) ; chi(2)=3.323, P=0.002],
      abnormal labor [65.82% (52/79) vs 34.18% (27/79) ; chi(2)=4.067, P=0.001] and
      abnormal fetal position [66.63% (26/39) vs 33.37% (13/39) ; chi(2)=3.002,
      P=0.013] were higher in women >=35 years old than in younger women. (5) Cesarean
      section during labor accounted for 33.77% (101/299) of stillbirth, including 76
      cases of emergency cesarean section or converted to cesarean section during
      labor. Conclusions: (1) The incidence of stillbirth in the 11 hospitals is high,
      and the causes are different at different gestational ages, therefore, different
      interventions are needed to reduce the incidence in different gestational weeks.
      Supervision of therapeutic induction should be strengthened <28 gestational
      weeks; standard management of pregnancy might decrease the occurrence of natural
      death >=28 weeks. (2) Attention should be paid to fetal body weight during
      pregnancy, especially FGR. (3) The stillbirth rate is high in elderly pregnant
      women, so it is important to strengthen the management of the elderly pregnant
      women.

PMID- 29325264
TI  - [High risk factors analysis of stillbirth].
AB  - Objective: To explore the high risk factors of stillbirth. Methods: 176 cases of
      stillbirth were collected in the Obstetrics and Gynecology Hospital of Fudan
      University from January 1(st), 2010 to December 31(st), 2016. All cases were
      analyzed retrospectively, including general profile, high risk factors of
      stillbirth in different years and pregnancy periods. Results: (1) The incidence
      of stillbirth was 0.178%(176/98 785). Stillbirth occured mostly at 28-28(+6)
      gestational weeks (10.8%,19/176), and the second peak was 29-29(+6)
      weeks(10.2%,18/176), while the third common period was 37-37(+6) weeks
      (9.1%,16/176). After 39 weeks, it maintained at a low level. (2) The top 5 high
      risk factors of stillbirth were infection (18.2%,32/176), unexplained
      (13.6%,24/176), hypertention disorders in pregnancy (13.1%, 23/176), umbilical
      cord torsion (12.5%, 22/176) and fetal malformations (10.2%, 18/176). (3) From
      2010 to 2012, the top 3 high risk factors were unexplained, the umbilical cord
      torsion and infection, while hypertention in pregnancy, infection and fetal
      malformation became the top 3 high risk factors after 2013. (4) Early stillbirth
      (20-27(+6) weeks) accounted for 21.6%(38/176); and unexplained (47.4%, 18/38),
      fetal edema (13.2%, 5/38),infection (13.2%, 5/38), umbilical cord torsion (5.3%,
      2/38) were the top 4 high risk factors. Late stillbirth (>=28 weeks) accounted
      for 78.4%(138/176), with infection (19.6%,27/138), hypertention in pregnancy
      (15.9%,22/138), umbilical cord torsion (14.5%,20/138) and fetal
      malformation(12.3%,17/138)being the top 4 high risk factors. Conclusions: More
      attention should be paid to maternal complications, especially infection and
      hypertension in pregnancy. Antenatal fetal monitoring, timely termination of
      pregnancy, standard management of stillbirth and looking for the causes may help
      reduce the incidence of stillbirth.

PMID- 29325265
TI  - [Clinical analysis of 105 intrauterine fetal deaths in 17 years].
AB  - Objective: To study the cause of intrauterine fetal death (IUFD) in 17 years.
      Methods: From June 1(st), 2000 to May 31(st), 2017, 65 621 women delivered in
      Peking University First Hospital. Clinical data of 105 cases of IUFD (including
      82 singleton pregnancies and 23 twin pregnancies) during the 17 years were
      analyzed retrospectively. Results: (1) In singleton pregnancies, the leading
      cause of IUFD was maternal complications, including severe pre-eclampsia (36/82,
      43.9%) and diabetes mellitus (6/82, 7.3%). The second reason was umbilical cord
      factors (13/82, 15.9%), including over-screwed umbilical cord, cord entanglement,
      true knot of cord. 54 women of singleton pregnancy (65.9%, 54/82) felt abnormal
      fetal movements (decreased or disappeared). (2) In twin pregnancies, the leading
      cause was complications of monochorionic twins (12/23, 52.2%). Seven woman of
      twin pregnancy (65.9%, 54/82) felt abnormal fetal movements. Conclusions: To
      reduce the occurrence of IUFD, the pregnancy complications should be managed in
      time and properly. Monochorionic twins should be determined as early as possible.
      More attention should be paid toabnormal fetal movement and the application of
      ultrasound.

PMID- 29325266
TI  - [Analysis of 649 cases of stillbirth in third trimester].
AB  - Objective: To analyze the risk factors of stillbirth in third trimester. Methods:
      Clinical data of 649 cases of stillbirth in third trimester were analyzed
      retrospectively in 22 hospitals of Haidian district from October 2011 to
      September 2016, including the incidence, the maternal profile, the perinatal care
      during pregnancy and the causes of stillbirth. Results: (1) The incidence of
      stillbirth in third trimester in Haidian district from October 2011 to September
      2016 was 0.293%(649/221 845). While the incidence in floating pregnant women
      (0.349%, 342/97 939) was higher than that in the residence (0.248%, 307/123 906),
      with statistically significant difference (chi(2)=19.178, P<0.01). The incidence
      of stillbirth in multiple pregnancy(0.201%, 89/4 264) was higher than that in
      singleton pregnancy (0.257%, 560/217 581), with statistically significant
      difference(chi(2)=4.690, P<0.01). There was no statistically significant
      difference in the incidence of stillbirth between male (0.300%, 347/115 632) and
      female fetuses (0.284%, 302/106 205; chi(2)=0.467, P>0.05).(2)Among the 649
      cases, the floating population accounted for the majority of those who never had
      prenatal visit (84.0%, 21/25), or less than 5 visits (80.7%, 125/155), or the
      first visit was beyond 13 gestational weeks(66.0%, 165/649). The causes of
      stillbirth in order were fetal factors (30.7%, 199/649), maternal factors(28.0%,
      182/649), umbilical cord factors (20.0%, 130/649), unexplained factors (17.6%,
      114/649) and placental factors (3.7%, 24/649). Birth defects, pregnancy
      hypertensive disorders, umbilical cord entanglement or torsion were the most
      important factors, accounting for 22.8%(148/649), 17.4%(113/649), 17.3%(112/649),
      respectively. Conclusions: The floating pregnant women are key population of
      stillbirth in third trimester. Maternal care and education should be strengthened
      in this population. The prevention of birth defect, better prenatal care in women
      with complications, and close monitor during labor are the key measures to reduce
      the incidence of stillbirth in third trimester.

PMID- 29325267
TI  - [Analysis of clinical outcomes of different embryo stage biopsy in array
      comparative genomic hybridization based preimplantation genetic diagnosis and
      screening].
AB  - Objective: To evaluate the efficiency of the application of array comparative
      genomic hybridization (array-CGH) in preimplantation genetic diagnosis or
      screening (PGD/PGS), and compare the clinical outcomes of different stage embryo
      biopsy. Methods: The outcomes of 381 PGD/PGS cycles referred in the First
      Affiliated Hospital of Nanjing Medical University from July 2011 to August 2015
      were retrospectively analyzed. There were 320 PGD cycles with 156 cleavage-stage
      biopsy cycles and 164 trophectoderm-biopsy cycles, 61 PGS cycles with 23 cleavage
      stage-biopsy cycles and 38 trophectoderm-biopsy cycles. Chromosomal analysis was
      performed by array-CGH technology combined with whole genome amplification.
      Single embryo transfer was performed in all transfer cycles. Live birth rate was
      calculated as the main clinical outcomes. Results: The embryo diagnosis rate of
      PGD/PGS by array-CGH were 96.9%-99.1%. In PGD biopsy cycles, the live birth rate
      per embryo transfer cycle and live birth rate per embryo biopsy cycle were
      50.0%(58/116) and 37.2%(58/156) in cleavage-stage-biopsy group, 67.5%(85/126) and
      51.8%(85/164) in trophectoderm-biopsy group (both P<0.01). In PGS biopsy cycles,
      the live birth rate per embryo transfer cycle and live birth rate per embryo
      biopsy cycle were the same as 34.8%(8/23) in cleavage-stage-biopsy group, the
      same as 42.1%(16/38) in trophectoderm-biopsy group (both P>0.05). Conclusions:
      High diagnosis rate and idea live birth rate are achieved in PGD/PGS cycles based
      on array-CGH technology. The live birth rate of trophectoderm-biopsy group is
      significantly higher than that of cleavage-stage-biopsy group in PGD cycles; the
      efficiency of trophectoderm-biopsy is better.

PMID- 29325270
TI  - [Research development of circulating tumor cell in ovarian epithelial carcinoma].

PMID- 29325269
TI  - [Research progress of brain derived neurotrophic factor in the pain of
      endometriosis].

PMID- 29325268
TI  - [Clinical significance of targeting drug-based molecular biomarkers expression in
      ovarian clear cell carcinoma].
AB  - Objective: To assess the expression level of targeting drug-based molecular
      biomarkers in ovarian clear cell carcinoma (OCCC) tissues and its clinical
      significance. Methods: A total of 63 OCCC patients included 40 primary OCCC and
      23 recurrent OCCC for secondary cytoreductive surgery (SCS), who had received
      primary surgeries at Fudan University Shanghai Cancer Center between January,
      2008 and December, 2015 were enrolled, and immunohistochemistry SP method was
      used to test human epidermal growth factor receptor (EGFR), human epidermal
      growth factor receptor-2 (HER2), aurora kinase A (AURKA), breast cancer
      susceptibility gene 1 (BRCA1), BRCA2 and programmed death-ligand 1 (PD-L1)protein
      expression in paraffin-embedded tissues. Results: The positive rates of EGFR,
      HER2, AURKA,BRCA1, BRCA2 and PD-L1 in primary and recurrent tumor tissues were
      respectively 20% (8/40) vs 30% (7/23) , 22% (9/40) vs 35% (8/23) , 38% (15/40) vs
      35% (8/23) , 42% (17/40) vs 39% (9/23) , 20% (8/40) vs 22% (5/23) , 25% (10/40)
      vs 17% (4/23) , and there were no significant differences between primary and
      recurrent OCCC (all P>0.05). chi(2)-test or Fisher exact analysis revealed that
      HER2 expression in recurrent tumor tissues had a relationship with
      chemoresistance (P<0.05), while the expression of other biomarkers showed no
      significant relationship with chemoresistance (all P>0.05). Further, Kaplan-Meier
      survival analysis showed that patients with HER2 and AURKA-positive expression
      had a significantly shorter progression-free survival time in primary OCCC (4
      months vs 10 months, log-rank test, P<0.05 for HER2; and 4 months vs 10 months,
      P<0.05 for AURKA); and a shorter overall survival time after SCS in recurrent
      OCCC (10 months vs 44 months, P<0.05 for HER2; and 13 months vs 43 months, P<0.05
      for AURKA). However, multivariate Cox proportional hazards regression analysis
      indicated that none of these 6 biomarkers was independent risk factor of
      progression-free survival time of primary OCCC or overall survival time after SCS
      for recurrent OCCC (P>0.05). Conclusion: HER2 and AURKA could serve as prognostic
      factors in ovarian clear cell carcinoma.

PMID- 29325271
TI  - [Research advances in primary biliary cholangitis].
AB  - Primary biliary cholangitis (PBC) is a chronic cholestatic disease with unknown
      pathogenesis. Positive anti-mitochondrial antibody has high sensitivity and
      specificity in the diagnosis of this disease. Ursodeoxycholic acid is mainly used
      for the treatment of PBC, but 40% of patients have an unsatisfactory biochemical
      response to this drug. 6-Ethylchenodeoxycholic acid is a new drug approved for
      the treatment of PBC, and liver transplantation remains the only effective method
      for the treatment of patients with end-stage PBC.

PMID- 29325272
TI  - [Advances in the treatment of primary biliary cholangitis].
AB  - Primary biliary cholangitis (PBC) is an autoimmune liver disease mainly involving
      intrahepatic interlobular bile ducts and can progress to liver fibrosis, liver
      cirrhosis, and even liver failure. Ursodeoxycholic acid (UDCA) is the first-line
      therapeutic drug for PBC and can delay disease progression, but as high as 40% of
      patients have suboptimal response to UDCA. Obeticholic acid, a farnesoid X
      receptor agonist, has been approved by FDA in May 2016 for patients who have no
      response to UDCA treatment or cannot tolerate such treatment. Other drugs such as
      fibrates, glucocorticoids, immunosuppressants, biological agents, and mesenchymal
      stem cells are gradually used in clinical practice and bring new hope to patients
      with refractory PBC.

PMID- 29325273
TI  - [How to understand the clinical significance of autoantibodies in primary biliary
      cholangitis].
AB  - Autoantibodies are important indicators for the diagnosis of primary biliary
      cholangitis (PBC). The autoantibodies in PBC patients are mainly
      antimitochondrial antibodies (AMAs) and antinuclear antibodies (ANAs). AMAs are
      one of the diagnostic indices of PBC. PBC-specific ANAs (nuclear dots or nuclear
      envelope, anti-sp100, and anti-gp210) have a high specificity in the diagnosis of
      AMA-negative PBC. This article reviews the clinical significance of these
      autoantibodies and analyzes some misconceptions about the clinical diagnosis of
      AMA-negative PBC and PBC-AIH overlap syndrome.

PMID- 29325274
TI  - [An interpretation of 2017 EASL clinical practice guidelines: the diagnosis and
      management of patients with primary biliary cholangitis].
AB  - Primary biliary cholangitis (PBC) is a chronic autoimmune cholestatic disease and
      may progress to liver fibrosis, liver cirrhosis, decompensated cirrhosis, and
      even end-stage liver disease without effective treatment. The diagnosis of PBC is
      mainly based on the biochemical parameters indicating cholestatic hepatitis and
      the presence of specific autoantibody in circulation. The goals of the treatment
      and management of PBC are to prevent the development of end-stage liver disease,
      to improve related clinical symptoms, and to improve patients' quality of life.
      Since PBC has relatively strong heterogeneity and the clinical manifestations and
      course of PBC can be diverse, it is necessary to provide long-term individualized
      treatment and follow-up for such patients. Here we provide an interpretation of
      the 2017 EASL Clinical Practice Guidelines for the diagnosis and management of
      patients with PBC, in order to better understand recent clinical research
      evidence and updated recommendations. In particular, we focus on the key points
      in the diagnosis, treatment, and follow-up strategies of PBC and emphasizing that
      timely and accurate risk stratification and proper clinical research enrollment
      may bring benefits to patients with refractory PBC.

PMID- 29325275
TI  - [Qualitative pathological assessment of liver fibrosis regression after antiviral
      therapy in patients with chronic hepatitis B].
AB  - Objective: To investigate the methods for qualitative pathological assessment of
      dynamic changes in liver fibrosis/cirrhosis after antiviral therapy in patients
      with chronic hepatitis B (CHB), since antiviral therapy can partially reverse
      liver fibrosis and cirrhosis caused by hepatitis B and semi-quantitative, rather
      than qualitative, pathological assessment is often used for the research on liver
      fibrosis regression. Methods: Previously untreated CHB patients with liver
      fibrosis and cirrhosis were enrolled, and liver biopsy was performed before
      treatment and at 78 weeks after the antiviral therapy based on entecavir. The
      follow-up assessment was performed once every half a year. Based on the
      proportion of different types of fibrous septum, we put forward the new
      qualitative criteria called P-I-R classification (predominantly progressive,
      predominantly regressive, and indeterminate) for evaluating dynamic changes in
      liver fibrosis. This classification or Ishak fibrosis stage was used to evaluate
      the change in liver fibrosis after treatment and Ishak liver inflammation score
      was used to evaluate the change in liver inflammation after treatment. Results: A
      total of 112 CHB patients who underwent liver biopsy before and after treatment
      were enrolled, and among these patients, 71 with an Ishak stage of >=3 and
      qualified results of live biopsy were included in the final analysis. Based on
      the P-I-R classification, 58% (41/71) were classified as predominantly
      progressive, 29% (21/71) were classified as indeterminate, and 13% (9/71) were
      classified as predominantly regressive; there were no significant differences
      between the three groups in alanine aminotransferase, aspartate aminotransferase,
      albumin, HBeAg positive rate, HBV DNA, and liver stiffness (P < 0.05). After
      treatment, the proportion of predominantly progressive, indeterminate, or
      predominantly regressive patients changed to 11% (8/71), 11% (8/71), and 78%
      (55/71), respectively. Among the 35 patients who had no change in Ishak stage
      after treatment, 72% (25/35) were classified as predominantly regressive and had
      certain reductions in the Laennec score, percentage of collagen area, and liver
      stiffness. Conclusion: This new P-I-R classification can be used to assess the
      dynamic changes in liver fibrosis after antiviral therapy in CHB patients.

PMID- 29325276
TI  - [A clinical study of antiviral therapy for patients with compensated hepatitis C
      cirrhosis].
AB  - Objective: To investigate the effect of antiviral therapy on the progression of
      liver cirrhosis and related predictive factors through a retrospective analysis
      of patients with compensated hepatitis C cirrhosis. Methods: The patients with
      compensated hepatitis C cirrhosis who were treated in our hospital from 2004 to
      2015 were divided into sustained virologic response (SVR) group, non-SVR (NSVR)
      group, and untreated group. The baseline features of patients with or without
      liver cirrhosis were compared to identify the predictive factors for the
      progression of liver cirrhosis. The changes in platelet count, spleen sizes,
      Model for End-Stage Liver Disease (MELD) score, Sequential Organ Failure
      Assessment (SOFA) score, and Child-Turotte-Pugh (CTP) score were analyzed, and
      the incidence rate of liver cancer was compared between groups. A one-way
      analysis of variance, the Kruskal-wallis H test, the two-independent-sample t
      test, the chi-square test, and a multivariate logistic regression analysis were
      used for data analysis based on data type. Results: A total of 89 patients with
      compensated liver cirrhosis were enrolled, among whom 42 received the antiviral
      treatment with interferon and ribavirin (30 were treated with pegylated
      interferon-alpha and 12 were treated with ordinary interferon) and 47 did not
      receive any antiviral therapy. Among the patients who received the antiviral
      treatment with interferon and ribavirin, 20 achieved SVR and 22 did not achieve
      SVR. Compared with baseline values, platelet count in the SVR group and the NSVR
      group was increased by (44.93 +/- 32.66)*10(9)/L and (9.73 +/- 28.83)*10(9)/L,
      respectively, and platelet count in the untreated group was reduced by (19.76 +/-
      54.5)*10(9)/L; the three groups had a significant change in platelet count (F =
      14.731, P < 0.001). Spleen size was reduced by 0.91 +/- 1.09 cm in the SVR group
      and increased by 0.20+/-0.84 cm and 1.11 +/- 1.69 cm in the NSVR group and the
      untreated group, respectively; the three groups had a significant change in
      spleen size (F = 14.943, P < 0.001). The three groups had no significant changes
      in MELD, SOFA, and CTP scores (P > 0.05). One patient (5.00%) in the SVR group, 5
      (22.73%) in the NSVR group, and 6 (12.77%) in the untreated group progressed to
      liver cancer (chi (2) = 13.787, P = 0.001). The univariate analysis showed that
      SVR, HCV RNA, total bilirubin, and albumin were predictive factors for disease
      progression, and the multiple logistic regression analysis demonstrated that SVR
      and total bilirubin were predictive factors for disease progression. Conclusion:
      Interferon combined with ribavirin has a marked clinical effect in the treatment
      of compensated hepatitis C cirrhosis with good short- and long-term efficacy.

PMID- 29325277
TI  - [Effect of Fuzheng Huayu capsules on survival rate of patients with liver
      cirrhosis].
AB  - Objective: To investigate the effect of Fuzheng Huayu capsules on the survival
      rate of patients with liver cirrhosis. Methods: A retrospective analysis was
      performed for the clinical data of the patients with various types of liver
      cirrhosis who were hospitalized in Shuguang Hospital Affiliated to Shanghai
      University of Traditional Chinese Medicine from January 1, 2006 to December 31,
      2008. The data collected for these patients included their basic information,
      diagnosis and treatment, and results of laboratory examination. The Kaplan-Meier
      method was used to analyze the effect of Fuzheng Huayu capsules on the survival
      rate of patients with liver cancer. The starting point of observation was the
      first day of the patient's admission and the ending point of follow-up
      observation was the date of death or the end of follow-up April 1, 2014. The cut
      off value was obtained if the patient did not experience any outcome event
      (death) at the end of follow-up. With reference to the outcome, the time when the
      outcome occurred, and the cut-off value, the life-table method was used to
      calculate survival rates and survival curves were plotted. The Kaplan-Meier
      product-limit method was used to calculate the arithmetic mean of survival time
      and median survival time, and the log-rank test was used to compare the survival
      data. Results: A total of 430 patients with liver cirrhosis were enrolled, among
      whom 191 died and 239 survived or were censored. The average constituent ratio of
      death was 55.6% and the average constituent ratio of survival was 44.4%. The life
      table method showed that the half-, 1-, 2-, and 5-year survival rates were 70%,
      64%, 58%, and 48%, respectively. The median survival time was 112.1 weeks for the
      patients who did not take Fuzheng Huayu capsules and 351.6 weeks for those who
      did, and there was a significant difference in survival rate between the two
      groups (P = 0.000). Among 313 patients who had an etiology of hepatitis B, 164
      did not take Fuzheng Huayu capsules and had a median survival time of 195.9 weeks
      and a 5-year survival rate of 44%, and 149 took Fuzheng Huayu capsules and had a
      median survival time of 336.9 weeks and a 5-year survival rate of 59%; there was
      a significant difference in survival rate between the two groups (P = 0.038).
      Among 117 patients who did not have hepatitis B, 68 did not take Fuzheng Huayu
      capsules and had a median survival time of 78.1 weeks and a 5-year survival rate
      of 32%, and 49 took Fuzheng Huayu capsules and had a median survival time of
      277.4 weeks and a 5-year survival rate of 53%; there was a significant difference
      in survival rate between the two groups (P = 0.013). Among 92 patients with
      compensated liver cirrhosis, 47 did not take Fuzheng Huayu capsules and had a 5
      year survival rate of 65%, and 45 took Fuzheng Huayu capsules and had a 5-year
      survival rate of 82%; both groups of patients had a median survival of 440 weeks;
      there was a significant difference in survival rate between the two groups (P =
      0.027). Among 338 patients with decompensated liver cirrhosis, 185 did not take
      Fuzheng Huayu capsules and had a median survival time of 60.3 weeks and a 5-year
      survival rate of 33%, and 153 took Fuzheng Huayu capsules and had a median
      survival time of 267.7 weeks and a 5-year survival rate of 51%; there was a
      significant difference in survival rate between the two groups (P = 0.001).
      Conclusion: Fuzheng Huayu capsules can improve the prognosis of patients with
      liver cirrhosis and increase their survival rates and have good long-term
      efficacy.

PMID- 29325278
TI  - [Effect of cannabinoid receptor-2 agonist AM1241 on platelet-derived growth
      factor expression in the liver tissue of mice with hepatic fibrosis].
AB  - Objective: To investigate the effect of cannabinoid receptor-2 (CB2) agonist
      AM1241 on the mRNA and protein expression of platelet-derived growth factor
      (PDGF) and collagen-III (Col-III) in the liver tissue of mice with experimental
      liver fibrosis induced by carbon tetrachloride (CCl(4)). Methods: Totally 38 8
      week-old male C57BL/6J mice were randomly divided into control group, model
      group, 3 mg/kg CB2 receptor agonist (AM1241) group, and 9 mg/kg AM1241 group. All
      mice, except for the control group, were treated with 30% CCl(4) (three times a
      week, 5 ml/kg body weight, 16 weeks) to establish a liver fibrosis model.
      Meanwhile, 3 and 9 mg/kg AM1421 was intraperitoneally injected for daily
      intervention, respectively. The dosage was adjusted according to actual body
      weight. The same solvent was given in the control group. The serum level of
      aspartate aminotransferase (AST) was measured by serum enzyme digestion. The
      liver inflammation and fibrosis were observed by HE staining of tissue slices.
      The mRNA and protein expression of PDGF and Col-III in hepatic tissue was
      determined by real-time PCR and immunohistochemistry. Results: Compared with the
      control group, the mice in model group showed severe liver fibrosis,
      significantly elevated serum AST level (742 +/- 300.8 U/L vs 118.1 +/- 31.1 U/L,
      P < 0.05), and significantly increased mRNA and protein expression of PDGF and
      Col-III in liver tissue (P < 0.05). Compared with the model group, the mice in 3
      mg/kg AM1241 group and 9 mg/kg AM1241 group had less severe liver fibrosis, and
      significantly reduced serum AST levels (116.6 +/- 13.68 U/L vs 742 +/- 300.8 U/L,
      P < 0.05; 113.8 +/- 16.01 U/L vs 742 +/- 300.8 U/L, P < 0.05) and mRNA and
      protein expression of PDGF and Col-III in liver tissue (P < 0.05). Conclusion:
      CB2 receptor agonist AM1241 can inhibit the mRNA and protein expression of PDGF
      in the liver tissue of mice with hepatic fibrosis, and reduce extracellular
      matrix synthesis.

PMID- 29325279
TI  - [Characteristics of IgH-CDR3 repertoire of peripheral B cells in a patient with
      primary biliary cholangitis: a preliminary study using high-throughput
      sequencing].
AB  - Objective: To analyze the characteristics of immunoglobulin heavy chain
      complementarity-determining region (IgH-CDR3) repertoire of peripheral B cells in
      a patient with primary biliary cholangitis (PBC) and to investigate the diversity
      of the immune system. Methods: Arm-PCR was used to amplify the IgH-CDR3 region of
      circulating B cells isolated from a PBC patient, and high-throughput sequencing
      was used to analyze the amplified product. The characteristics of immune
      repertoire were analyzed by bioinformatics. Results: In total, 329219 sequence
      reads were generated from the sample, with 325540 total CDR3 sequences and 72774
      distinct CDR3 sequences, and the D50 of IGH-CDR3 was 7.7. The dominant CDR3
      length of the sample was 45 nt (9.6%); the N addition with the highest frequency
      ranged from 13 to 14 nt (5.25%); the J trimming with the highest frequency was 0
      nt (12.7%); the three most frequent V alleles were V4-59 (9.5%), V3-23 (8.1%),
      and V1-69 (6.4%). Conclusion: The diversity of IgH-CDR3 repertoire is relatively
      low in this patient with PBC, with several B-cell clonal expansions. The
      specificity needs to be further verified after increasing the sample size.

PMID- 29325280
TI  - [Clinical value of anti-liver/kidney microsomal-1 antibody in patients with liver
      disease].
AB  - Objective: To investigate the clinical and laboratory features of patients with
      liver disease and positive anti-liver/kidney microsomal-1 (anti-LKM-1) antibody,
      and to provide a reference for clinical diagnosis and differential diagnosis.
      Methods: The clinical data of patients with positive anti-LKM-1 antibody who were
      treated in our hospital from 2006 to 2016 were collected, and clinical and
      laboratory features were analyzed and compared. An analysis was also performed
      for special cases. Results: The measurement of related autoantibodies was
      performed for about 100 thousand case-times, and 15 patients were found to have
      positive anti-LKM-1 antibody. Among the 15 patients, 7 were diagnosed with type 2
      autoimmune hepatitis (AIH) with an age of 11.0 +/- 9.0 years and were all
      adolescents with acute onset; 8 were diagnosed with hepatitis C with an age of
      51.5 +/- 9.0 years, among whom 7 were middle-aged patients and 1 was a child aged
      12 years, and all of them had an insidious onset. Compared with the patients with
      hepatitis C, the AIH patients had significantly higher levels of alanine
      aminotransferase (1 003.9 +/- 904.3 U/L vs 57.0 +/- 84.1 U/L, P < 0.05),
      aspartate aminotransferase (410.7 +/- 660.3 U/L vs 34.9 +/- 42.9 U/L, P < 0.05),
      and total bilirubin (98.0 +/- 191.0 MUmol/L vs 15.4 +/- 6.0 MUmol/L, P < 0.05).
      There was a reduction in immunoglobulin G after the treatment with
      immunosuppressant, compared with the baseline. Of all 8 patients with hepatitis
      C, 6 received antiviral therapy with interferon and ribavirin, and 5 out of them
      achieved complete response, among whom 4 had a reduction in the level of anti-LKM
      1 antibody after treatment; however, a 12-year-old child developed liver failure
      after interferon treatment and died eventually. Conclusion: Positive anti-LKM-1
      antibody is commonly seen in patients with type 2 AIH or hepatitis C, but there
      are differences between these two groups of patients in terms of age, disease
      onset, liver function, and the level of anti-LKM-1 antibody. The hepatitis C
      patients with a confirmed diagnosis and exclusion of autoimmune hepatitis can
      achieve good response to interferon under close monitoring, even if anti-LKM-1
      antibody is positive. As for adolescent patients with hepatitis C and positive
      anti-LKM-1 antibody, the possibility of AIH should be excluded.

PMID- 29325281
TI  - [Value of hydrogen proton magnetic resonance spectroscopy in the determination of
      liver triglyceride in patients with fatty liver disease and its influencing
      factors].
AB  - Objective: To investigate the value of 1H-magnetic resonance spectroscopy ((1)H
      MRS) in determining the content of liver triglyceride in patients with fatty
      liver disease (FLD), as well as its influencing factors. Methods: A total of 124
      patients with nonalcoholic fatty liver disease (NAFLD), chronic hepatitis B
      (CHB), or hepatitis B complicated by FLD who underwent liver biopsy in the
      Affiliated Hospital of Hangzhou Normal University were enrolled, and the clinical
      data, serological markers, FibroScan results, and (1)H-MRS results were
      collected. A correlation analysis was performed with the results of liver biopsy
      as the gold standard, and the influence of factors including hepatitic B virus
      (HBV) infection and obesity on accuracy was analyzed. A one-way analysis of
      variance was used for comparison of means between the three groups, and the LSD
      or SNK test (for homogeneity of variance) or the Tamhane's or Dunnett's test
      (heterogeneity of variance) was used for comparison between any two groups. The t
      test was used for comparison of continuous data between groups, and the chi
      square test was used for comparison of categorical data. The MRS-PDFF receiver
      operating characteristic (ROC) curve was plotted, the area under the ROC curve
      (AUC) was calculated, the optimal cut-off points for the diagnosis of NAFLD were
      estimated, and sensitivity and specificity were calculated. Results: The NAFLD
      group (42 patients) and the CHB + NAFLD group (40 patients) had a significantly
      higher proton density fat fraction (PDFF, the content of triglyceride in the
      liver) than the CHB group (42 patients) (16.84+/-9.76/9.39 +/- 5.50 vs 3.45 +/-
      1.63, P < 0.001). The results were significantly correlated with the degree of
      steatosis confirmed by liver biopsy (P < 0.001), but it was not significantly
      correlated with inflammation or fibrosis grade. The correlation analysis showed
      that the MRS-PDFF value measured by 1H-MRS was significantly correlated with body
      mass index (BMI), blood lipids, alkaline phosphatase, and blood glucose, while it
      was not significantly correlated with age, sex, or the presence or absence of
      hepatitis B. The ROC curve analysis showed that the AUCs of PDFF measured by 1H
      MRS were 0.93, 0.974, and 0.976, respectively, for the diagnosis of steatosis
      S1(>=5%), S2(>=34%), and S3(>=66%), and the corresponding optimal thresholds were
      5.14%, 11.16%, and 16.7%, respectively. Conclusion: 1H-MRS has a high diagnostic
      value in quantitative evaluation of the degree of liver steatosis in patients
      with FLD and is not affected by the factors such as HBV infection, age, and sex,
      while it is correlated with BMI and lipid metabolism.

PMID- 29325282
TI  - [An evolutionary analysis of HCV genotype 6 in Li people in Hainan Province,
      China].

PMID- 29325283
TI  - [Upper gastrointestinal bleeding caused by exfoliative esophagitis in one patient
      with hepatitis B cirrhosis].

PMID- 29325284
TI  - [Risk factors and therapeutic strategies for primary biliary cholangitis patients
      with poor prognosis].
AB  - With the progress in detection methods and the update of diagnostic and
      therapeutic concepts, more and more patients with primary biliary cholangitis
      (PBC) have been diagnosed and treated. A high proportion of PBC patients,
      however, progress to liver decompensation, with an increased risk of liver
      transplantation and death and a significant reduction in long-term survival.
      These patients need early diagnosis and urgent treatment. This article discusses
      how to identify the PBC patients with poor prognosis early from the aspects of
      biochemical response, disease features, and biomarkers, and reviews the progress
      in related complementary therapies and new drugs including Ocaliva, Fibrates,
      UDCA-derived drugs, and molecular targeted drugs.

PMID- 29325285
TI  - [Primary biliary cholangitis and bile acid metabolism].
AB  - Primary biliary cholangitis (PBC) is an immune-mediated cholestatic liver disease
      of unknown pathogenesis. The research on immunologic injury in the past helps us
      to understand more about this disease, but there are still many problems and
      challenges in the research on PBC. With a focus on the cholestatic features of
      PBC, this article reviews the research advances in bile acid metabolism in the
      field of PBC, in order to provide new thoughts for future research.

PMID- 29325286
TI  - [Research advances in the role of the Hippo-YAP/TAZ signaling pathway in primary
      liver cancer].
AB  - The Hippo-YAP/TAZ signaling pathway is an evolutionarily conserved pathway, which
      has been confirmed to play an important role in organ volume control, stem cell
      function, tissue regeneration, and tumorigenesis. Recent research findings show
      that the Hippo-YAP/TAZ signaling pathway is closely associated with the
      development and progression of primary liver cancer, and inhibition of the
      activity of this pathway may be a new method for the treatment of liver cancer.
      This article reviews the research advances in the role of the Hippo-YAP/TAZ
      signaling pathway in primary liver cancer.

PMID- 29325287
TI  - [The diagnostic value and limits of diagnostic parameters for Wilson's disease].
AB  - Wilson disease (WD) is a rare and treatable genetic disorder. This paper
      describes the new advances and author's long-term experiences in the diagnosis of
      WD. The characteristics in clinical and routine tests are: the age of
      presentation can be quite broad, the WD could not be excluded based on age only;
      the patients usually have mild digestive symptoms but obvious chronic liver
      disease signs; liver function tests may reveal normal or a mild elevation in
      bilirubin, ALT and AST, but quite abnormal in serum albumin and prothrombin time
      in most patients; Coombs-negative hemolytic anemia, normal or markedly subnormal
      serum alkaline phosphatase (typically < 40 IU/L) are useful for the diagnosis of
      fulminant WD. In china, Kayser-Fleischer rings are present in 72.2% of patients
      at the time of diagnosis, the positive rate is significantly higher in patients
      with a neurological presentation (93.4%) than patients presenting with liver
      disease (63.3%), however, they are usually absent in children under 6 years old,
      occasionly present in patients with chronic cholestatic liver disease. The mean
      serum ceruloplamin level in WD patients is 71.1 +/- 48.7 mg/L, the level is < 200
      mg/L in 98.9% of patients, < 100 mg/L in about three fourths patients, < 50 mg/L
      in about half patients, but it may be low in 50% of patients with severe end
      stage liver disease of any etiology too, and even lower than 50 mg/L in patients
      with nephritic syndrome. Basal 24-hour urinary copper excretion may be>=100 g at
      presentation in 86.7% of patients with WD, but also in 22% of Patients with
      certain chronic liver diseases, the sensitivity of penicillamine challenge test
      is lower than basal urinary copper excretion, however, the specificity is
      significantly higher than former (97% versus 78%). Hepatic copper determination
      remains the gold standard for the diagnosis of WD. We have designed a standard
      method for hepatic copper determination. The most useful cut-off value is 209 g/g
      dry wt using our method, with the sensitivity of 99.4%, and specificity of 96.1%.
      However, long-standing hepatic failure and or obstruction can cause heptic copper
      elevations into the WD area. In recent years, direct complete DNA sequencing has
      become easy, rapid, less expensive and commercially available. Currently reported
      mutation detection rate is 90%, the specificity is almost 100%. The limitation to
      the method has been the ability to identify all the affected alleles in suspected
      individuals. If no mutation is identified, the diagnosis of WD could not be
      excluded. None of the laboratory parameters alone allows a definite diagnosis of
      WD. The WD diagnostic scoring system based on a composite of key parameters helps
      clinicians to gauge the degree of certainty of the diagnosis: WD scores greater
      than 4, the diagnosis of WD is highly likely; score 0 or 1, the diagnosis is
      unlikely. However, the WD diagnosis could not be excluded in suspected patients
      who do not perform genetic test and hepatic copper determination. Patients with
      chronic cholestatic liver disease may have scores more than 4.

PMID- 29325288
TI  - [Diagnosis, management, and treatment of hepatocellular carcinoma (V2017)].

PMID- 29325289
TI  - [Optimal treatment regimen for patients with HBeAg-positive chronic hepatitis B
      after suboptimal response to 24 weeks of Peg-IFN alpha-2a].
AB  - Objective: To investigate the optimal treatment regimen for patients with HBeAg
      positive chronic hepatitis B (CHB) after suboptimal response to 24 weeks of
      pegylated interferon (Peg-IFN) alpha-2a. Methods: A total of 188 patients with
      HBeAg-positive CHB who had suboptimal response to 24 weeks of Peg-IFN alpha-2a
      were randomly divided into entecavir group (n = 93) and telbivudine group (n =
      95). The two groups received entecavir 0.5 mg/d and telbivudine 0.6 g/d,
      respectively, for 208 weeks. After 208 weeks of treatment, the following indices
      were assessed: HBeAg clearance rate and seroconversion rate, hepatitis B virus
      (HBV) DNA clearance rate (HBV DNA < 500 IU/ml), safety, and drug resistance rate.
      The data were subjected to intention-to-treat (ITT) analysis and per protocol
      (PP) analysis. Univariate and multivariate logistic regression analyses were
      performed for the drugs used and baseline characteristics in patients with or
      without HBeAg seroconversion, and stratification analysis was performed based on
      the baseline HBeAg level. Results: Six cases in the entecavir group and four
      cases in the telbivudine group did not complete the treatment. Sequential
      entecavir and telbivudine were well tolerated and safe for all patients. There
      was a significant difference in HBV DNA clearance rate at 52 weeks of treatment
      between the entecavir group and the telbivudine group (ITT analysis: 93.55%
      [87/93] vs 77.89% [74/95], chi (2) = 9.363, P = 0.002; PP analysis: 93.10%
      [81/87] vs 76.92% [70/91], chi (2) = 9.049, P = 0.003). The suppression rates of
      HBV DNA at 208 weeks of treatment were 95.70% (89/93) vs 92.63% (88/95) (ITT
      analysis) and 95.40% (83/87) vs 92.31% (84/91) (PP analysis). There was a
      significant difference in HBeAg seroconversion rate at 208 weeks of treatment
      between the entecavir group and the telbivudine group (ITT analysis: 38.71%
      [36/93] vs 62.11% [59/95], chi (2) = 10.290, P = 0.001; PP analysis: 41.38%
      [36/87] vs 64.84% [59/91], chi (2) = 9.833, P = 0.002). Univariate and
      multivariate logistic regression analyses suggested that sequential use of
      telbivudine, male sex, and the baseline level of HBeAg were significantly
      associated with HBeAg seroconversion at 208 weeks of treatment (P = 0.003, hazard
      ratio [HR] = 0.386; P = 0.009, HR = 0.303; P = 0.001, HR = 3.502). Conclusion:
      For patients with HBeAg-positive CHB after suboptimal response to 24 weeks of Peg
      IFNalpha-2a, sequential use of telbivudine is the optimal treatment regimen
      according to the baseline level of HBeAg (baseline guidance). The incidence of
      HBeAg seroconversion during 208 weeks of sequential treatment can be
      significantly increased according to the HBeAg decline curve in early treatment
      (24 weeks) and 104 weeks (response guidance).

PMID- 29325290
TI  - [Effect of hepatitis C virus nonstructural protein 5A and its domains II on
      hepatocyte gluconeogenesis in mice].
AB  - Objective: To investigate the role of hepatitis C virus nonstructural protein 5A
      (NS5A) and its domains I, II, and III in regulating gluconeogenesis in mice and
      the underlying mechanism. Methods: A total of 60 male C57BL/6J mice were randomly
      divided into six groups. Recombinant lentiviral particles with specific
      expression of full-length NS5A, NS5A domain I, NS5A domain II, or NS5A domain III
      were injected via the caudal vein to establish a mouse model, and the group
      without injection and the group with the injection of the lentiviral particles
      containing enhanced green fluorescent protein (EGFP) were established as negative
      control. The effect of full-length NS5A protein and its domains on fasting blood
      glucose (FBG) and fasting serum insulin (FINS) were measured. Liver tissue was
      collected to prepare a paraffin section. Immunohistochemistry was used to measure
      the expression of phosphoenolpyruvate carboxykinase (PEPCK) in hepatocytes,
      quantitative real-time PCR and/or Western blot were used to measure the
      expression of NS5A, phosphorylated adenosine monophosphate-activated protein
      kinase (p-AMPK), sterol regulatory element-binding protein-1 (SREBP-1), and
      PEPCK. Results: Compared with the group without injection and the group with the
      injection of the lentiviral particles containing EGFP, the groups with the
      injection of the lentiviral particles containing full-length NS5A and NS5A domain
      II had significant increases in FBG and homeostasis model assessment of insulin
      resistance index (P < 0.01). Immunohistochemistry and quantitative real-time PCR
      showed a significant increase in the expression of PEPCK, a key enzyme involved
      in gluconeogenesis. Western blot showed that full-length NS5A protein and NS5A
      domain II inhibited the level of p-AMPK and increased the levels of SREBP-1 and
      PEPCK. Conclusion: NS5A protein and NS5A domain II may affect glucose metabolism
      in hepatocytes in mice by regulating AMPK/SREBP-1/PEPCK, and NS5A domain II may
      play an important role in insulin resistance in hepatocytes caused by HCV
      infection.

PMID- 29325291
TI  - [Hepatitis B core antigen promotes invasion of hepatocellular carcinoma cell line
      HepG2.2.15 via Toll-like receptor 4].
AB  - Objective: To investigate the effect of hepatitis B core antigen (HBcAg) in
      promoting the invasion of hepatitis B virus (HBV)-related hepatocellular
      carcinoma cell line HepG2.2.15 and the role of Toll-like receptor 4 (TLR4) in the
      mechanism. Methods: TLR4 mRNA and protein expression in HepG2 cells and
      HepG2.2.15 cells was measured by reverse transcription real-time PCR and Western
      blot analysis, respectively. HepG2.2.15 cells were transfected with TLR4 specific
      small interfering RNA (siRNA) to silence TLR4 expression, and stimulated by
      recombinant HBcAg in culture. The invasion of cells was measured by Transwell
      invasion assay. The expression of TLR4 signaling pathway-related proteins in the
      cultured cells and proinflammatory cytokines in the supernatant was also
      determined. The student's t-test, one-way ANOVA, and SNK-q test were used for
      statistical analysis. Results: TLR4 mRNA and protein expression in HepG2.2.15
      cells was significantly higher than that in HepG2 cells. TLR4 siRNA transfection
      remarkably down-regulated TLR4 expression in HepG2.2.15 cells. Inhibiting TLR4
      expression and/or HBcAg stimulation did not affect the proliferation of
      HepG2.2.15 cells. However, HBcAg stimulation significantly increased the invasion
      ability of HepG2.2.15 cells and the secretion of proinflammatory cytokines
      [including interferon (IFN)-gamma, interleukin (IL)-6, IL-8, and tumor necrosis
      factor (TNF)-alpha]. Inhibiting TLR4 expression significantly reduced HBcAg
      induced cellular invasion. Meanwhile, HBcAg stimulation elevated the expression
      of MyD88 and TRIF in HepG2.2.15 cells. TLR4 silencing inhibited HBcAg-induced
      increase in the expression of MyD88, while it showed no significant impact on
      TRIF expression. Conclusion: HBcAg can promote the invasion of HepG2.2.15 cells.
      The TLR4/MyD88 signaling pathway may be involved in this process by inducing the
      expression of proinflammatory cytokines.

PMID- 29325292
TI  - [Therapeutic effect of transcatheter arterial chemoembolization combined with
      ultrasound-guided microwave ablation for treatment of liver cancer in special
      sites].
AB  - Objective: To investigate the efficacy and clinical value of transcatheter
      arterial chemoembolization (TACE) combined with ultrasound-guided microwave
      ablation for the treatment of liver cancer in special sites. Methods: The
      patients with liver cancer in special sites (the liver cancer was adjacent to the
      gallbladder, dome of diaphragm, gastrointestinal tract, heart, great vessels, and
      portal vein, with the shortest distance from the tumor to the organ/lumen < 0.5
      cm ) were enrolled as treatment group, and the patients with primary liver cancer
      in normal sites treated in our hospital during the same period were randomly
      enrolled as control group. They underwent TACE combined with ultrasound-guided
      microwave ablation. The 6-month, 12-month, 18-month and 24-month survival rates
      of the patients in two groups were analyzed. Results: The clinical data of 40
      patients with liver cancer in special sites, including 9, 7, 5, 11, 3, 3, and 2
      patients with liver cancer adjacent to the gallbladder, dome of diaphragm,
      gastrointestinal tract, portal vein, hepatic vein, inferior vena cava, and heart,
      respectively, and another 40 patients in control group were collected in the
      study. The negative rate of alpha-fetoprotein (AFP) was 83.3% in the treatment
      group and 82.8% in the control group. The 6-month, 12-month, 18-month, and 24
      month survival rates were 100.0%, 95.0%, 90.0%, and 80.0%, respectively, in the
      treatment group, and 100.0%, 97.5%, 92.5%, and 85.0%, respectively, in the
      control group. Conclusion: TACE combined with ultrasound-guided microwave
      ablation is as effective for liver cancer in special sites as for those in normal
      sites, with high safety, and is feasible in clinical application.

PMID- 29325293
TI  - [Expression of miR-212 and miR-132 in serum of patients with primary liver cancer
      and their targeted regulation of GP73].
AB  - Objective: To investigate the expression of miR-212 and miR-132 in the serum of
      patients with primary liver cancer and their targeted regulation of GP73.
      Methods: The patients with liver cancer, chronic hepatitis B, or liver cirrhosis
      who were hospitalized in Taizhou People's Hospital from January 2015 to December
      2016 were enrolled, and healthy volunteers were also enrolled as controls.
      Quantitative real-time PCR was used to measure the serum levels of miR-212 and
      miR-132, and the association between the expression of serum miR-212 and miR-132
      and the clinicopathological features of patients with liver cancer was analyzed.
      A Spearman's rank correlation analysis was used to analyze the correlation
      between serum miR-212/miR-132 and GP73. Western blot was used to measure the
      protein expression of GP73, and MTT assay was used to measure the survival rate
      of cells. The Levene's homogeneity of variance test was used for data analysis.
      The independent samples t-test was used for comparison of means between two
      samples, and ANOVA was used for comparison of means between multiple samples.
      Results: A total of 90 patients with liver cancer, 60 with chronic hepatitis B,
      68 with liver cirrhosis, and 100 healthy volunteers were enrolled. The relative
      expression levels of miR-212 and miR-132 in serum were 0.046 6 +/- 0.024 7 and
      0.005 9 +/- 0.003 0 in the patients with liver cancer, 0.979 7 +/- 0.259 5 and
      1.001 8 +/- 0.249 9 in the healthy volunteers, 0.588 2 +/- 0.216 5 and 0.345 7 +/
      0.233 8 in the patients with hepatitis, and 0.313 8 +/- 0.153 3 and 0.080 1 +/-
      0.042 66 in the patients with liver cirrhosis. Compared with the normal controls,
      all patients had significant reductions in the expression of serum miR-212 (t =
      10.26, 20.86, and 35.80, all P < 0.01) and miR-132 (t = 16.55, 36.09, and 39.85,
      all P < 0.01). In the patients with liver cancer, the relative expression of miR
      212 and miR-132 was negatively correlated with alpha-fetoprotein (miR-212: t = 
      4.46, P < 0.01; miR-132: t = -4.83, P < 0.01), TNM stage (miR-212: t = 6.569, P <
      0.01; miR-132: t = 7.31, P < 0.01), degree of tumor differentiation (miR-212: t =
      5.268, P < 0.01; miR-132: t = 5.914, P < 0.01), and presence of portal vein tumor
      thrombus (miR-212: t = 5.16, P < 0.01; miR-132: t = 3.681, P < 0.01), while it
      was not correlated with tumor size (miR-212: t = 0.687, P > 0.05; miR-132: t =
      0.887, P > 0.05). In addition, serum miR-212 and miR-132 were negatively
      correlated with GP73 in the patients with liver cancer (miR-212: r(s) = -0.709, P
      < 0.01; miR-132: r(s) = -0.877, P < 0.01). Overexpression of miR-212 or miR-132
      in HepG2 cells significantly inhibited the activity and expression of 3'-UTR, and
      interference of miR-212 or miR-132 significantly increased the activity and
      expression of 3'-UTR in GP73. Overexpression of GP73 reversed the reduction in
      survival rate of hepatoma cells induced by the overexpression of miR-212 or miR
      132. Conclusion: Patients with liver cancer have a significant reduction in the
      expression of miR-212 and miR-132 in serum, which is closely associated with the
      development, progression, and metastasis of liver cancer, and miR-212 and miR-132
      in hepatoma cells inhibit the growth of liver cancer by targeted regulation of
      GP73 expression.

PMID- 29325294
TI  - [Effects of Lactobacillus paracasei N1115 combined with fructooligosaccharides on
      non-alcoholic fatty liver disease induced by high-fat diet in mice].
AB  - Objective: To investigate the effects of Lactobacillus paracasei N1115 combined
      with fructooligosaccharides (FOS) on non-alcoholic fatty liver disease (NAFLD) in
      mice and its possible mechanism. Methods: A total of 50 male C57 mice were
      randomly and equally divided into five experimental groups. Group 1 received a
      normal diet (ND). Other four groups received a high-fat diet (HFD) to establish
      NAFLD models. In addition to HFD, group 3 received Lactobacillus paracasei N1115
      (2.2*10(9) CFU/mL), group 4 received FOS (4 g/kg per day), and group 5 received
      Lactobacillus paracasei N1115 (2.2*10(9) CFU/mL) and FOS (4 g/kg per day). All
      groups received continuous intervention for 16 weeks. The following indices were
      measured for all groups after intervention: general condition, the levels of
      fasting blood glucose, insulin, and lipopolysaccharide (LPS), and the levels of
      tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, and interferon
      (IFN)-gamma in the serum and liver. The mRNA levels of Toll-like receptor (TLR)4,
      nuclear factor (NF)-kappab, insulin receptor (InsR), and insulin receptor
      substrate (IRS)-1 were measured by real-time RT-PCR. The data were subjected to
      one-way analysis of variance and comparison between groups was made by Bonferroni
      method. Results: Compared with group 2, groups 3, 4, and 5 had significantly
      lower body weight, Lee's index, liver index, and the levels of blood glucose and
      insulin resistance (P < 0.05). The serum level of LPS in group 2 was
      significantly higher than that in the other experimental groups (group 1: 8.80 +/
      0.85 U/L, group 3: 12.31 +/- 1.01 U/L, group 4: 12.27 +/- 0.98 U/L, and group 5:
      10.17 +/- 0.79 U/L vs group 2: 15.45 +/- 1.14 U/L, F = 55.117, P < 0.001). The
      levels of TNF-alpha, IL-1beta, IL-6, and IFN-gamma in the serum and liver in
      group 2 were also significantly higher than those in the other groups (P < 0.05).
      Group 2 had significantly higher mRNA levels of TLR4 and NF-kappab in the liver
      than the other groups (F = 82.933, P < 0.001; F = 149.033, P < 0.001); however,
      it had significantly lower mRNA levels of InsR and IRS-1 in the liver than the
      other groups (F = 33.347, P < 0.001; F = 70.225, P < 0.001). Conclusion:
      Lactobacillus paracasei N1115 combined with FOS can reduce the level of LPS in
      the blood circulation, inhibit activation of the LPS/TLR4 signaling pathway, and
      reduce the release of inflammatory factor and the body's insulin resistance, so
      it can relieve NAFLD.

PMID- 29325295
TI  - [A study on the value of 10 tumor markers in diagnosis of primary hepatic
      carcinoma].

PMID- 29325296
TI  - [Clinical features and treatment of acute fatty liver of pregnancy complicated by
      acute liver failure].

PMID- 29325297
TI  - [Sofosbuvir combined with daclatasvir in treatment of a patient with hepatitis C
      virus infection undergoing liver and renal transplantation: a case report].

PMID- 29325298
TI  - [A case of glycogen storage disease type II and related analysis].

PMID- 29325299
TI  - [Hepatitis C-related hepatocellular carcinoma and the treatment with direct
      acting antiviral agents].
AB  - With the wide use of direct-acting antiviral agents (DAAs), more and more
      patients with chronic hepatitis C achieve sustained virological response;
      however, no consensus has been reached on the application of DAAs in the
      treatment of hepatitis C virus-related hepatocellular carcinoma (HCC). This
      article summarizes and evaluates related issues in this field, including whether
      antiviral therapy with DAAs in patients with hepatitis C can increase the
      incidence or recurrence rate of HCC, as well as whether DAAs can be used for
      hepatitis C in HCC patients after antitumor treatment and the efficacy of DAAs in
      such patients.

PMID- 29325300
TI  - [Clinical significance of quantitative level of hepatitis B core antibody].
AB  - Hepatitis B core antibody (anti-HBc) targets viral core protein and is produced
      in patients with hepatitis B virus (HBV) infection, and seroconversion occurs in
      the early stage of infection and often lasts for a lifetime. Qualitative
      detection of anti-HBc has been used in clinical practice for many years, while
      the clinical significance of its quantitative level remains unclear. A novel anti
      HBc immunoassay based on double-antigen sandwich ELISA has been developed in
      recent years and lays a foundation for illustrating the change in the
      quantitative level of anti-HBc (qAnti-HBc) in HBV infection and its clinical
      significance. Several recent studies have revealed that qAnti-HBc is associated
      with the degree of hepatitis activity and response to pharmacotherapy and may
      become an important basis for selecting antiviral drugs, optimizing therapeutic
      regimen, and predicting treatment outcome.

PMID- 29325301
TI  - [Role of CD36 in nonalcoholic fatty liver disease].
AB  - Nonalcoholic fatty liver disease (NAFLD) includes nonalcoholic simple fatty
      liver, nonalcoholic steatohepatitis, liver cirrhosis, and liver cancer and is the
      most common liver disease in the world. The complex pathogenesis of NAFLD is a
      major concern among researchers. CD36 is a transmembrane glycoprotein that takes
      up fatty acid and binds to oxidized low-density lipoprotein in the liver, and
      therefore, it is involved in the development and progression of NAFLD. With
      reference to the latest research findings, this article reviews the association
      between CD36 and NAFLD and the role of CD36.

PMID- 29325302
TI  - [Research advances in pathogenesis of autoimmune hepatitis].
AB  - Autoimmune hepatitis (AIH) is liver parenchymal inflammation mediated by the
      autoimmune response of hepatocytes. Its clinical features include elevation of
      aminotransferases in serum, presence of various autoantibodies in circulation,
      hypergammaglobulinemia, and interface hepatitis in liver tissue. Although the
      etiology and pathogenesis of AIH have not been fully elucidated, a consensus has
      been reached on the theories of "genetic susceptibility" and "molecular
      simulation" , and "immunoregulatory disorder" remains a hot research topic for
      many scholars. This article reviews the research advances in the theories of
      "genetic susceptibility" , "molecular simulation" , and "immunoregulatory
      disorder" .

PMID- 29325303
TI  - [Standardize the management of asthma exacerbation, and improve the treatment
      level of acute attack].

PMID- 29325304
TI  - [The Chinese experts' consensus on the evaluation and management of asthma
      exacerbation].
AB  - Asthma exacerbations can do a lot of harm to the patients and consume large
      amounts of medical resources. This consensus is based on the domestic and foreign
      guidelines and literatures to standardize the evaluation and management of asthma
      exacerbations in China. Asthma exacerbations are characterized by a progressive
      increase in symptoms of shortness of breath, cough, wheezing or chest tightness
      and progressive decrease in lung function, and usually require modification of
      treatment. Recognizing risk factors and triggering factors of asthma
      exacerbations is helpful for the prevention and long-term management. Evaluation
      of asthma exacerbations is based on symptoms, lung function, and arterial blood
      gas. Management is stratified according to the severity of disease. Different
      regimens to treat asthma exacerbations are discussed in this consensus.
      Glucocorticoids should be used properly. Overuse of antibiotics should be
      avoided. Management of life-threatening asthma is discussed separately. Special
      attention should be paid in some special respects, such as asthma during peri
      operation period, gestation period, and childhood. Diagnosis and management of
      complications are also of great significance and are discussed in details.

PMID- 29325305
TI  - [Evaluation of asthma management from the surveys in 30 provinces of China in
      2015-2016].
AB  - Objective: To evaluate the general level of asthma management in urban areas of
      China and further promote the national asthma management plan. Methods: A multi
      center, cross-sectional survey was carried out in 30 provinces of China (except
      for Tibet) during Oct 2015 to May 2016. It's a questionnaire-based face-to-face
      survey which included asthma management using peak flow meter (PFM) and pulmonary
      function test, medication choice of maintenance therapy and asthma education.
      Results: A total of 3 875 asthmatic outpatients were recruited including 2
      347(60.6%) females and 1 528(39.4%) males. The mean age was (50.7+/-16.7) years
      ranging from 14 to 99. Only 10.1%(388/3 837) patients used PFM as monitoring,
      whereas 62.1%(2 405/3 874) patients underwent pulmonary function test during the
      past year. There were 57.4%(2 226/3 875) patients treated with inhaled cortical
      steroid plus long-acting beta(2)-agonist combinations (ICS+LABA) as daily
      medication. 43.3%(1 661/3 836) patients were followed up by physicians. Among
      this population, 1 362 asthmatic outpatients were recruited, who also took part
      in the asthma control survey in 2007-2008 in 10 cities. In this subgroup,
      17.9%(244/1 360) were tested by PFM and 66.6%(907/1 362) by pulmonary function
      test during last year. As to the medication, 63.1%(860/1 362) selected ICS+LABA
      for daily control. There were 50.4%(685/1 359) patients in the follow-up cohort
      by physicians. Compared to the similar survey conducted in 2007-2008, the
      proportion of patients with ICS+LABA regimen and follow-up by physicians were
      markedly higher, while the rate of PFM use did not have significant improvement.
      Conclusion: Although the present level of asthma management in China is still far
      from ideal, asthma management has improved compared to 8 years ago. Yet the use
      of PFM does not significantly improve. Asthma action plan and application of PFM
      should be further promoted to improve the level of asthma management.

PMID- 29325306
TI  - [A retrospective study of the inducing factors and clinical characteristics of
      patients hospitalized for asthma exacerbation in China in 2013-2014].
AB  - Objective: To study the inducing factors and clinical characteristics of patients
      hospitalized for asthma exacerbation in China. Methods: Patients hospitalized for
      asthma exacerbation at 29 hospitals in China were retrospectively recruited
      during 2013-2014. Results: Clinical data of 3 240 asthmatic patients were
      collected and analyzed including 1 369(42.3%) males and 1 871(57.7%) females. The
      patients hospitalized for asthma exacerbation counted for 2.95% (6 375/215 955)
      of all patients hospitalized during the same period. The leading six inducing
      factors, in sequence, were acute upper respiratory tract infection [42.3%(1 370/3
      240)], changes of weather [22.8%(738/3 240)], noxious gas [(4.3%(140/3 240),
      allergy challenges [3.5%(115/3 240)], strenuous exercise [1.8%(57/3 240)], and
      air pollution [1.5%(49/3 240)]. In older patients, more exacerbations were
      induced by weather changes, yet less sensitive to allergy challenges. As to
      middle-aged patients, they were less sensitive to upper respiratory tract
      infections, however the difference was not statistically significant (P>0.05). In
      winter more asthma patients were induced by upper respiratory tract infections,
      while in autumn more patients were induced by weather changes, strenuous exercise
      and air pollution. In spring and summer more patients were induced by allergy
      challenges, but the differences failed to achieve statistical significance
      (P>0.05). In northern cities more patients were induced by upper respiratory
      infections, whereas in southern cities more by noxious gases. Allergy challenges
      and air pollution tended to affect more patients in northern cities, but the
      difference was of no significance (P>0.05). The differences of inducing factors
      among patients of different gender, with or without a smoking history, and with
      different exacerbation severity didn't show any statistical significance. The
      patients with severe and life-threatening exacerbations counted for 20.1% (652/3
      240). The percentage of patients older than 60 years was higher in patients with
      severe or life-threatening exacerbations than in whose with mild or moderate
      exacerbations, so did the percentage of male patients, of patients with disease
      duration longer than 10 years, with smoking history, and with a history of
      hospitalization or emergency department visits due to asthma exacerbation during
      the last year. Conclusion: The acute upper respiratory tract infection ranks top
      among all the inducing factors. Senility, male gender, long duration of disease,
      smoking history, and a history of frequent hospital visits might be the risk
      factors for severe or life-threatening asthma exacerbations.

PMID- 29325307
TI  - [The clinical characteristics, diagnosis and treatment of patients with gout in
      China].
AB  - Objective: To investigate the demographic characteristics, clinical features,
      diagnosis and treatment of patients with gout in China. Methods: Clinical data of
      6 814 patients with gout from 100 hospitals in 27 provinces, municipalities or
      autonomous regions in China were collected and analyzed. Results: (1) The ratio
      of male to female in patients with gout was 14.7?1. The mean age of onset was
      (48.8+/-15.1) years old. Mean serum urate level was (526.7+/-132.3) MUmol/L.
      Patients' education background was of U-shaped distribution; (2) Hypertension was
      the most common comorbidity [15.8%(1 079/6 814)], then overweight or obesity
      [51.9%(3 536/6 814)]; (3) Alcohol and high-purine food intake were dominant
      triggering factors in men. The diagnosis of gout was made after onset in majority
      of patients with cardinal symptom arthralgia. Most patients had the disease less
      than 5 years, and the longer the course, the more flares in the previous year of
      entry; (4) Febuxostat was the mostly used urate-lowering medication. 20.7%(1
      412/6 814), 10.8%(739/6 814) and 3.9%(265/6 814) of patients were followed up in
      4 weeks, 12 weeks and 24 weeks after registration, and 18.9%(267/1 412),
      29.1%(215/739) and 38.1%(101/265) of them reached the control target of serum
      urate levels, respectively. After treatment, patients' liver function was not
      affected, but serum creatinine levels decreased significantly. Conclusions: The
      proportion of gout patients who reach target serum urate level is very low.
      Further steps including education and survey need to be carried on.

PMID- 29325308
TI  - [Opportunistic infection in systemic lupus erythematosus patients: the disease
      spectrum and the characteristics of peripheral lymphocyte subsets].
AB  - Objective: To investigate the common opportunistic infections and the
      characteristics of peripheral lymphocyte subsets in patients with systemic lupus
      erythematosus (SLE). Methods: From December 2013 to December 2016, peripheral
      lymphocyte subsets were consecutively detected by flow cytometry in treated SLE
      patients with or without opportunistic infections (OIs) . The lymphocyte subsets
      in healthy donors were used as normal control group. Results: A total of 145
      treated SLE patients were enrolled including 108 with OIs and 37 without OIs. The
      common OIs were cytomegalovirus (CMV) diseases (66/108), Pneumocystis jirovecii
      pneumonia (PJP, 16/108), other fungal infections (16/108), Epstein-Barr virus
      (EBV, 15/108) and tuberculosis (14/108). Compared with treated SLE without OIs,
      total lymphocyte, CD(4+) T, and CD(8+) T lymphocyte counts were significantly
      reduced in SLE with OIs [1 260 (780, 1 810) cells/MUl vs. 565 (399, 1 043)
      cells/MUl, P<0.001; 485 (280, 811) cells/MUl vs. 173 (95, 327) cells/MUl,
      P<0.001; 464 (339, 764) cells/MUl vs. 265 (158, 424) cells/MUl, P=0.003,
      respectively]. Conclusions: The common OIs in treated SLE patients were CMV
      diseases, PJP, other fungi, EBV and tuberculosis. OIs are prone to develop in SLE
      patients with severe lymphocytopenia, especially CD(4+) T cell depletion.

PMID- 29325309
TI  - [Association of Crohn's disease with aryl hydrocarbon receptor gene polymorphisms
      and haplotypes].
AB  - Objective: To explore the relationship of Crohn's disease (CD) susceptibility to
      aryl hydrocarbon receptor (AhR) polymorphisms and haplotypes in Han population in
      Wenzhou city, China. Methods: A total of 310 CD patients and 573 age- and sex
      matched healthy controls were enrolled in our study. Three single nucleotide
      polymorphisms (SNPs) of AhR(rs10249788,rs2158041,rs2066853) were determined by
      the improved multiple ligase detection reaction technique. Unconditional logistic
      regression analyses was applied to analyze the allelic and genotypic differences
      of each SNP between CD patients and controls, as well as their influence on the
      clinicopathologic characteristics in CD patients. Analyses of linkage
      disequilibrium and haplotype were performed by Haploview 4.2 software in all
      study subjects. Results: Compared with the controls, the variant allele (T) and
      genotype (CT+TT) of (rs2158041) were evidently decreased among CD patients
      (19.52% vs. 25.04%, P=0.009; 34.19% vs. 44.68%, P=0.003). According to "the
      Montreal Classification Standards" , CD patients were divided into different
      subgroups. The variant allele (T) and genotype (CT+TT) of (rs2158041) were
      significantly lower in patients with terminal ileum CD than in controls (16.79%
      vs. 25.04%, P=0.005; 28.24% vs. 44.68%, P=0.001). Similar conclusions were also
      drawn in patients with constricting disease when compared with the controls
      (15.20% vs. 25.04%, P=0.003; 28.43% vs. 44.68%, P=0.003). The three SNPs above
      were shown to be in a linkage disequilibrium. Compared with the controls
      respectively, the frequency of haplotype (CCG) was increased in CD patients
      (44.73% vs. 39.60%, P=0.039), whereas that of haplotype (CTG) was decreased
      (18.02% vs. 22.78%, P=0.047). Conclusions: AhR (rs2158041) variation might
      influence the risk as well as the location and behavior of CD. The haplotype
      (CCG) possibly increase the risk of CD development, whereas haplotype (CTG) might
      decrease it.

PMID- 29325310
TI  - [Clinical characteristics and whole exon sequence study of a Chinese family with
      autosomal dominant lateral temporal lobe epilepsy].
AB  - Objective: To explore the genetic characteristics in a Chinese family with
      autosomal dominant lateral temporal lobe epilepsy (ADLTE) and analyze the
      correlation between genotype and phenotype. Methods: The natural history,
      clinical data and peripheral blood sample were collected in all patients and two
      healthy members of this ADLTE family. Whole exon sequence (WES) analysis strategy
      was used to explore the underlying mutations. Possible causative genetic
      variation was further confirmed by direct PCR and Sanger sequencing. The genotype
      phenotype features were compared with previously reported cases. Results: A novel
      pathogenetic LGI1 frameshift mutation p.T134fs was identified in this study. The
      clinical phenotype was different from reported. Conclusion: This study reports a
      pathogenic LGI1 mutation in a Chinese ADLTE family for the first time, which
      suggests that LGI1 is a new genetic abnormality of ADLTE in Chinese.

PMID- 29325311
TI  - [Effects of trimetazidine, a myocardial metabolism agent, on regulating 5
      hydroxytrytamine system of rats with myocardial infarction and/or depression].
AB  - Objective: 5-Hydroxytrytamine (5-HT) system was reported to be associated with
      myocardial infarction (MI) and depression. The aim of the present study was to
      study the effect of trimetazidine on 5-HT in MI and/or depression rats. Methods:
      Ninety rats were divided into three groups: trimetazidine, sertraline and saline
      groups (n=30 in each group), and pretreated with trimetazidine, sertarline, or
      saline, respectively, by gavage once a day for 4 weeks. Thereafter, each group
      was further divided into three subgroups: MI subgroup, depression subgroup, and
      MI+ depression subgroup. Serum 5-HT, platelet 5-HT, 5-HT(2A) receptor (5
      HT(2A)R), and serotonin transporter (SERT) were detected by enzyme linked
      immunosorbent assay. Results: Similar to sertarline, comparing to saline,
      trimetazidine treatment increased serum 5-HT [(221+/-23) pg/ml vs. (176+/-11)
      pg/ml; (395+/-31) pg/ml vs. (195+/-5) pg/ml; (348+/-28) pg/ml vs. (183+/-10)
      pg/ml], platelet 5-HT [(305+/-22) pg/ml vs. (130+/-27) pg/ml; (252+/-18) pg/ml
      vs. (175+/-5) pg/ml; (241+/-26) pg/ml vs. (181+/-11) pg/ml], and platelet 5
      HT(2A)R levels [(247+/-13) pg/ml vs. (197+/-12) pg/ml; (320+/-13) pg/ml vs.
      (193+/-18)pg/ml; (334+/-17) pg/ml vs. (206+/-15) pg/ml]), and lowered platelet
      SERT levels [(248+/-11) pg/ml vs. (323+/-36) pg/ml; (188+/-7) pg/ml vs. (278+/
      20) pg/ml; (170+/-23) pg/ml vs. (282+/-22) pg/ml] in MI, depression and MI+
      depression subgroups, respectively (all P< 0.05). When compared the effect of
      trimetazidine and sertarline treatment, serum 5-HT and platelet 5-HT(2A)R in MI
      group were significantly lower in trimetazidine than in sertraline group
      (P<0.05), while serum 5-HT and platelet 5-HT, 5-HT(2A)R in depression group rats
      were significantly higher in trimetazidine than in sertraline group
      (P<0.05).Interestingly, platelet 5-HT(2A)R in MI+ depression rats was much higher
      in trimetazidine than in sertraline group (P<0.05). Conclusions: Trimetazidine, a
      kind of myocardial metabolism agent, could play a role on the regulation of 5-HT,
      5-HT(2A)R, and SERT levels in rats with MI and/or depression.

PMID- 29325312
TI  - [Outcomes of alternative donor allogeneic hematopoietic stem cell transplantation
      for Fanconi anemia: a five cases report].
AB  - Five patients with Fanconi anemia who received hematopoietic cell transplantation
      were retrospectively analyzed. The conditioning regimens included fludarabine,
      cyclophosphamide and anti-thymocyte globulin. Two patients received both bone
      marrow and peripheral blood stem cells as the source of stem cell grafts from
      haploidentical matched related donors, while the others received peripheral blood
      stem cells from unrelated donors. All patients tolerated well and reached
      hematopoietic reconstitution. One patient died of intracranial infection. During
      follow-up, 4 patients survived independent of transfusion with full donor
      chimerism.

PMID- 29325313
TI  - [A case report of idiopathic hypereosinophilic syndrome with pulmonary embolism].

PMID- 29325314
TI  - [A case of lymphangiomatosis with initial gastrointestinal symptoms].

PMID- 29325315
TI  - [Standardized diagnosis and treatment of pituitary prolactinoma: lesson from a
      case of pituitary adenoma with slightly elevated prolactin level].

PMID- 29325316
TI  - [A topic about Takotsubo syndrome].

PMID- 29325317
TI  - [An update on clinical research of argyrophilic grain disease].

PMID- 29325318
TI  - [The role of sphingosine-1-phosphate and its receptors in autoimmune diseases].

PMID- 29325319
TI  - [Application of half-dose spectral CT based on the automatic spectral imaging
      mode selection and adaptive statistical iterative reconstruction in the CT
      examination of upper abdomen in obese patients.]
AB  - Objective: To investigate the value of combined use of half-dose spectral CT
      based on the automatic spectral imaging mode selection (GSI Assist) and adaptive
      statistical iterative reconstruction (ASIR) in the CT examination of upper
      abdomen in obese patients as compared with conventional CT. Methods: Eight-two
      obese patients (body mass index>=29 kg/m(2)) were prospectively selected from
      October to December 2016, and contrast-enhanced CT during arterial phase (AP) and
      portal venous phase (PVP) were carried out in those patients.The patients were
      randomly assigned to the study group and control group with random number table
      (41 cases in each group). In the study group, half-dose spectral CT based on GSI
      Assist was applied and monochromatic images (40 to 70 keV, 10 keV as increment)
      were reconstructed using 50% ASIR (group A). In the control group, the fixed tube
      potential of 120 kVp was done with images reconstruction using 30% ASIR (group
      B). Quantitative parameters of radiation dose, CT value, contrast to noise ratio
      (CNR) and image noise were compared between the two groups by using two sample t
      test, while qualitative visual parameters (overall image quality as graded on a 5
      point scale) were compared with Mann-Whitney U test. Results: There was
      significant difference in effective radiation dose between the two groups[(5.2+/
      0.8) vs (10.4+/-1.7) mSv, t=-17.822, P<0.001], and it was decreased for 50% in
      group A. During the arterial phase (AP) and portal venous phase (PVP), at the
      energy level of 40 keV and 50 keV, higher CT values, higher or similar CNRs,
      higher image noise and lower overall image quality scores were found in group A
      when compared with group B. At the energy level of 60 keV, group A had higher CT
      values, higher or similar CNRs, similar overall image quality scores with higher
      or similar image noise as compared with group B. At the energy level of 70 keV,
      the two groups had similar CT values, CNRs and image noise, and higher overall
      image quality scores were found in group A. Conclusions: In obese patients,
      combined use of half-dose spectral CT based on GSI Assist and ASIR can reduce
      effective radiation dose up to 50% when compared with conventional upper
      abdominal CT.Monochromatic images at 70 keV can maintain CNR and improve overall
      image quality.

PMID- 29325320
TI  - [Anatomy research of cervical laminoplasty with preservation of the posterior
      ligament complex.]
AB  - Objective: To evaluate the feasibility of cervical laminoplasty with preservation
      of the posterior ligament complex for enlarging the spinal canal. Methods: Six up
      to-standard human corpse specimens were divided into two groups by simple
      randomization (start from C4 group, S4; start from C5 group, S5; 3 corpses in
      each group). Decompression operation of C3-C6 level was performed in a
      predetermined sequence by using the new procedure with preservation of the
      posterior ligament complex.The basic depth of spinal canal was measured with a
      depth gauge at fixed point after the right bone groove of single level was
      completed.The operation of the contralateral bone groove was continued, and then
      the spinal canal was measured again when the spinous process was pulled backward
      by using a tissue forceps until the ligament complex was just tight.Retreat value
      (RV) of vertebral lamina was obtained by calculating the difference between the
      two measurements.The earlier measured levels needed to be remeasured when the
      operation area increased by one level. Two independent sample and one-sample t
      test were used to analyze the measurement results. Results: RV of vertebral
      lamina was small after finishing the first level of the decompression operation
      [S4: (0.87+/-0.72) mm; S5: (1.83+/-0.29) mm], and the value reached its maximum
      after the completion of C3-C6 level.The overall average RVmaxs from C3 to C6
      level were (2.37+/-0.52) mm, (4.27+/-0.78) mm, (3.73+/-0.93) mm and (2.16+/-0.77)
      mm, respectively.The overall average retreat rates (RR) were 17%+/-7%, 32%+/-9%,
      29%+/-10% and 16%+/-6%, respectively. The overall average RVmax of C4 and C5
      level reached or exceeded the decompression threshold value of 4 mm (t=0.839, 
      0.703, both P>0.05). The average RVmax of C4/C5 level was similar in the two
      groups (t=-1.204, 1.189, both P>0.05); however, the difference of average RVmax
      between C3 and C6 level was significant (t=-4.429, 4.196, both P<0.05).
      Conclusions: Cervical laminoplasty with preservation of the posterior ligament
      complex can enlarge the sagittal diameter of spinal canal and relieve the
      compression of spinal cord.In addition, RV of each level increases as the number
      of the operation level increases, and the ability of vertebral lamina to retreat
      is quite different from C3 to C6 level.The decompression effect in the middle of
      the operation area is better than that on the cranial and tail side.

PMID- 29325321
TI  - [Preliminary applicability evaluation of Prostate Imaging Reporting and Data
      System version 2 diagnostic score in 3.0T multi-parameters magnetic resonance
      imaging combined with prostate specific antigen density for prostate cancer].
AB  - Objective: To investigate the preliminary applicability of Prostate Imaging
      Reporting and Data System version 2 (PI-RADS v2) score in the condition of 3.0T
      multi-parametric magnetic resonance imaging (Mp-MRI) combined with clinical
      classic indicators for the diagnosis of prostate cancer (PCa). Methods: The
      clinical and MRI materials of 247 patients of suspicious prostate disease treated
      in Second Affiliated Hospital of Soochow University from June 2015 to November
      2016 were analyzed retrospectively, including 110 cases with PCa and 137 cases
      without cancer.All cases underwent the high-resolution axial T(2)-weighted
      imaging (T(2)WI), diffusion weighted imaging (DWI) and dynamic contrast
      enhancement-magnetic resonance imaging (DCE-MRI) and were confirmed
      pathologically by puncture biopsies.The Mp-MRI materials of all cases were scored
      according to PI-RADS v2.The prostate volume and prostate specific antigen (PSA)
      density (PSAD) value were calculated according to the formulas.The univariate and
      multivariate analysis were performed for the observed indicators (age, prostate
      volume, PSA, PSAD and PI-RADS v2 score) to determine the independent predictors
      for PCa.Then, a Logistic regression model (combined prediction model) was
      established by the independent predictors for combined diagnosis of PCa.The
      receiver operating characteristic curve (ROC) curve analysis was performed to get
      the sensitivity and specificity of each independent predictor and the model to
      diagnose PCa.The differences of AUC values of each independent predictor and the
      model were compared with each other to evaluate the diagnostic performance for
      PCa. Results: The differences in the age, prostate volume, PSA, PSAD and the PI
      RADS v2 score between patients with PCa and non-cancer group were all
      statistically significant (t=2.870, Z=-4.230, -7.787, -9.477, -10.826, all
      P<0.05). The PSAD and PI-RADS v2 score were independent predictors for PCa
      (OR=3.331, 10.546, both P<0.05). The Logistic regression combined prediction
      model by PI-RADS v2 score and PSAD to forecast PCa was Logit(P)=-5.097+
      2.309*PSAD+ 1.214*PI-RADS v2 score.The area under the curve (AUC) of ROC in the
      combined model (0.911) was higher than that in the PI-RADS v2 score (0.886) and
      PSAD (0.851) and the differences were all statistically significant (Z=2.416,
      2.716, both P<0.05); but the difference in the AUC value between PI-RADS v2 score
      and PSAD was not statistically significant (Z=1.191, P=0.234). The diagnostic
      sensitivity of PSAD, PI-RADS v2 score and the model were: 0.891, 0.782 and 0.855,
      respectively; the specificity were 0.449, 0.912 and 0.847, respectively on their
      positive thresholds (0.15 MUg.L(-1).ml(-1,) 4 and -0.82). Conclusion: PI-RADS v2
      score combined with PSAD in diagnosing PCa is superior to the single application
      of them and it can lead to high diagnostic sensitivity and specificity for PCa.

PMID- 29325322
TI  - [A retrospective study of tumor and fertility outcomes after fertility-sparing
      surgical treatment of patients with borderline ovarian tumors].
AB  - Objective: To study tumors and fertility outcomes after fertility-sparing
      surgical treatment with borderline ovarian tumors (BOT). Methods: One hundred and
      nineteen patients with BOT enrolled from 3 hospitals between January 2004 and
      January 2017 were analysed retrospectively.The clinical data and follow-up
      results were obtained and analyzed. Results: Among the 119 BOT patients, 55
      patients underwent fertility-sparing surgery.The median age was 43 years
      (interquartile range: 15-80 years). There were 103 patients (86.55%) in stage I,
      and 16 patients (13.45%) in stage II and above.The median follow up time was 68
      months (range: 4-155). (1)Tumor outcomes: 13 patients recurred and 3 patients
      died.Progression free survival (PFS) and the overall survival rate had no
      significant difference between the two groups (85.45% vs 92.19% P=0.309, 96.4% vs
      98.4% P=0.492). PFS was related to FIGO stage, invasive implantation and
      chemotherapy by univariate analysis (P<0.05). The multivariate Cox regression
      model analysis showed that FIGO stage and invasive implantation were independent
      prognostic factors for PFS (P<0.05). (2) Pregnancy outcomes: 28 patients had a
      planned for pregnancy in fertility-sparing group, with 13 (46.43%) of them were
      pregnancy. Conclusions: FIGO stage and invasive implantation were the important
      factors of prognosis.Fertility-sparing surgery is safe and feasible to preserve
      the fertility of young patients.

PMID- 29325323
TI  - [Platelet to lymphocyte ratio in peripheral blood and body mass index: novel
      independent prognostic factors in patients with melanoma].
AB  - Objective: To investigate whether platelet to lymphocyte ratio (PLR) in
      peripheral blood and body mass index (BMI) can be independent prognostic factors
      in patients with melanoma. Methods: Clinical date of 140 patients with melanoma
      in the Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer
      Hospital from January 1, 2010 to December 31, 2015 were analyzed
      retrospectively.Receiver operating characteristic (ROC) curve was performed the
      optimal cut-off value for PLR.The 140 patients were divided into high PLR group
      and low PLR group.According to "Guidelines for prevention and control of
      overweight and obesity in Chinese adults" , the patients were divided into high
      BMI group and low BMI group.The relationship between PLR, BMI with overall
      survival (OS), progression free survival (PFS) and disease free survival (DFS)
      were analyzed.The Kaplan-Meier method and Log rank test was used for univariate
      survival analysis and Cox proportional hazards regression model for multivariate
      analysis. Results: The optimal cut-off value of PLR determined by ROC curve was
      PLR=120.15, and BMI threshold was 24.Univariate survival analysis showed that
      PLR, BMI and clinical stage were the factors affecting the OS in patients
      (P<0.05). The median survival time (MST) was 21 months in the whole group and 17
      months in the high PLR group, 34 months in the low PLR group, respectively; the
      MST in the high and low BMI group were 29 months and 13 months, respectively.The
      difference was statistically significant (P<0.05). The effects of PLR and BMI on
      PFS and DFS were not statistically significant.Cox multivariate analysis showed
      that PLR, BMI and clinical stage were independent prognostic factors of OS
      (P<0.05). And BMI was the only independent protective factor for OS, the risk of
      death decreased by 0.611 times, with each unit increased for BMI.Clinical
      subgroup analysis showed that PLR also was risk factor to the prognosis of
      patients with stage II, III, and IV (P<0.05). Conclusions: PLR is an independent
      prognostic risk factor for patients with melanoma, and BMI is an independent
      protective factor.PLR and BMI are important factors in prognostic evaluation of
      melanoma.

PMID- 29325324
TI  - [Obstetric outcome in pregnancy complained with pulmonary hypertension].
AB  - Objective: To identify whether pregnancy outcomes vary by the severity of
      pulmonary hypertension. Methods: A retrospective study was conducted on 78 cases
      of pregnancies complained with pulmonary hypertension who delivered in the First
      Affiliated Hospital, Sun Yat-sen University from 2006 to 2016.The selected cases
      were divided into three groups according to severity of pulmonary hypertension:
      mild pulmonary hypertension group (mild PAH group) was defined as a mean
      pulmonary artery pressure 30-49 mmHg, moderate pulmonary hypertension (moderate
      PAH group) as mean pulmonary artery pressure 50-69 mmHg and severe pulmonary
      hypertension (severe PAH group) as mean pulmonary artery pressure 70 mmHg or
      greater.The clinical features, risk pregnant complication, maternal and neonatal
      outcomes were described between these three groups.Analysis of variance, Chi
      square test was used for statistical analysis. Results: The average age of mild,
      moderate and severe PAH group were (31+/-5) years old, (31+/-5) years old and
      (27+/-3) years old, respectively (P=0.050). The rate of natural fertilization
      (P=0.414), parity (P=0.527) and gestational age (P=0.165) were similar in these
      three groups. In 78 pregnancies with pulmonary hypertension, 64.9% of pregnancies
      in mild PAH group was NYHA I, 50.0% of moderate PAH group was NYHA II and 54.5%
      of severe PAH group was NYHA III(P<0.001). There was no significant difference in
      the incidence of gestational diabetes mellitus (GDM, P=0.589), preeclampsia
      (P=0.942), premature rupture of membrane (PROM, P=0.276), scarred uterus
      (P=0.493) and postpartum hemorrhage (P=0.424). The cesarean section rate was
      84.2%, 90.0% and 63.6% in three groups (P=0.208). However, neuraxial anesthesia
      was performed in 82.5% of cases in mild PAH and 90.0% of cases in moderate PAH,
      while 27.3% of cases of severe PAH underwent neuraxial anesthesia (P<0.001). The
      fetal outcome was similar in there groups.But the rate of admission of NICU was
      significantly different in three groups (P=0.011). Conclusions: Maternal and
      neonatal outcomes was similar in different severity of pulmonary hypertension.But
      the severity of pulmonary hypertension affect the type of anesthesia.Close
      monitoring during pregnancy and timely termination of pregnancy can improve the
      outcome of pregnancy.

PMID- 29325325
TI  - [Expression of microRNA-155 in inflammatory bowel disease and its clinical
      significance].
AB  - Objective: To explore the expression of microRNA-155 in colonic mucosa and
      peripheral blood in patients with inflammatory bowel disease(IBD), and to examine
      the clinical value and significance of microRNA-155 in the diagnosis of IBD.
      Methods: Quatitative reverse-transcription PCR was performed to detect the
      expression of microRNA-155 in 20 patients with Crohn disease(CD), 21 patients
      with ulcerative colitis (UC), 18 patients with IBD type unclassified(IBDU), 25
      healthy people(control group), 12 patients with infection colitis and 19 patients
      with ischemia colitis.Receiver operating characteristic (ROC) curve was performed
      to analyze the clincal value of microRNA-155 in diagnosis of IBD. Results: The
      expression of microRNA-155 in colonic mucosa in CD, UC and IBDU group was
      significantly higher than that in control group(P<0.05). MicroRNA-155 expression
      was also significantly higher in UC group in comparison to CD group (35.4+/-3.0
      vs 18.6+/-5.9, P<0.01), IBDU group in comparison to CD group (23.0+/-3.7 vs
      18.6+/-5.9, P<0.05) and UC group in comparison to IBDU group (35.4+/-3.0 vs
      23.0+/-3.7, P<0.01). The plasma level of microRNA-155 in UC group (55.6+/-2.5)
      and IBDU group (48.1+/-6.2) was significantly higher than that in control
      group(P<0.05), while no significant difference in CD group was observed when
      compared with control group(P>0.05). ROC curve shows an AUC of 0.83 and 95%CI of
      0.679-0.986 of microRNA-155 expression in colonic mucosa.The sensitivity and
      specificity of microRNA-155 expression in colonic mucosa in diagnosis of IBD was
      68.4% and 78.6%, respectively. Conclusions: MicroRNA-155 showed high expression
      in colonic mucosa and peripheral blood in patients with IBD.MicroRNA-155 shows
      promise as a biomarker in diagnosis of IBD.Furthermore, the aberrant expression
      indicates that microRNA-155 may be involved in pathogenesis and progression of
      IBD.

PMID- 29325326
TI  - [Investigation of colistin resistance gene mcr in gut bacteria from patients with
      acute diarrheal].
AB  - Objective: To investigate the presence of colistin resistance gene mcr in gut
      bacteria from patients with acute diarrhea. Methods: Fresh stool samples were
      collected from 150 outpatients with acute diarrhea in the intestinal clinic of
      Henan Provincial People's Hospital, and were directly detected for the presence
      of mcr by PCR after enrichment in the broth.The mcr-producing bacteria were
      further isolated and identified by MALDI-TOF MS (Bruker Biotyper). Antimicrobial
      susceptibility of these isolates was conducted by micro-broth dilution method.The
      presence of other antimicrobial genes were investigated by PCR and sequencing.
      Results: Among the 150 cases of acute diarrhea, 4 patients(2.7%) were positive
      for mcr-1 gene, and only 1(0.7%) contained both mcr-1 and mcr-3.Four isolates of
      Escherichia coli and one isolate of Aeromonas veronii were obtained from the mcr
      positive cases.The presence of mcr-1 gene was found in all of the E. coli
      isolates, and the mcr-3 gene was identified in A. veronii. Conclusions: Our study
      demonstrated the relatively low prevalence of colistin resistant gene in the
      faeces of acute diarrhea outpatients, and mcr-1 is the dominant colistin
      resistant gene.The presence of mcr-3 gene was also found in the clinical sample,
      and it indicats the coexistence of mcr-1 and mcr-3 in the intestinal tract of
      diarrhea patient.We should pay attention to the potential transmission of these
      resistance genes and further investigations are urgently needed.

PMID- 29325327
TI  - [Resting-state network evaluation of chronic smokers by functional magnetic
      resonance imaging.]
AB  - Objective: To explore the neuromechanism of nicotine smoking, we use independent
      component analysis (ICA) of resting-state functional magnetic resonance imaging
      (fMRI) to investigate the differences of functional connectivity of resting-state
      networks (RSN) in chronic smokers. Methods: Forty-five chronic smokers and thirty
      four age and gender matched normal nonsmoking controls experienced resting-state
      fMRI scanning in 3.0T MRI scanner.Differences of the function connection in each
      RSN between chronic smokers group and nonsmoking controls group were analyzed by
      SPM software which was based on Matlab platform. Results: Compared with normal
      nonsmoking controls, changes of functional connectivity within each RSN in
      chronic smokers: (1) medial visual network: functional connectivity decreased in
      right cuneus (t=4.17, P<0.05) and left calcarine (t=3.08, P<0.05); (2) lateral
      visual network: decreased in left gyrus occipital superior (t=3.42, P<0.05); (3)
      occipital pole visual network: decreased in right gyrus occipital medius and left
      gyrus occipital medius (t=3.58, P<0.05); (4) dorsal attention network (DAN):
      increased in right gyrus occipital superior (t=3.42, P<0.05); (5) left
      frontoparietal network: decreased in left inferior parietal lobe (t=3.77,
      P<0.05); (6) right frontoparietal network: increased in right gyrus frontalis
      medius (t=3.42, P<0.05). Conclusion: There are some RSNs changes of chronic
      smokers compared with normal nonsmoking controls, with multiple brain regions
      functional connectivity abnormalities.

PMID- 29325328
TI  - [Value of split hand in the differential diagnosis of amyotrophic lateral
      sclerosis and cervical spondylotic amyotrophy].
AB  - Objective: To investigate the value of split hand in the differential diagnosis
      of amyotrophic lateral sclerosis(ALS) and cervical spondylotic amyotrophy (CSA).
      Methods: A total of 62 ALS patients, 57 CSA patients and 65 normal controls who
      visited the Neurology and Spine Department of Beijing Jishuitan Hospital from May
      2013 to June 2017 were enrolled into this study.The amplitudes of compound muscle
      action potentials (CMAP) were recorded from abductor digiti minimi (ADM) and
      abductor pollicis brevis (APB). Moreover, the ratio of CMAP amplitude between ADM
      and APB (ADM/APB) was calculated. Results: The ADM/APB of the ALS group (1.93+/
      1.97)was significantly higher than that of the normal control group (0.92+/
      0.22)(P<0.05); the ADM/APB of the CSA group (0.74+/-0.32)was significantly lower
      than that of the normal control group (0.92+/-0.22)(P<0.05); the ADM/APB of the
      ALS group (1.93+/-1.97)was significantly higher than that of the CSA group(0.74+/
      0.32)(P<0.05); the areas under receiver operator characteristic curve in patients
      with ALS was 0.843, the diagnostic sensitivity and specificity for ALS were 75.8%
      and 83.1% with the cutoff value of ADM/APB=1.077; the areas under receiver
      operator characteristic curve in patients with CSA was 0.737, the diagnostic
      sensitivity and specificity for CSA were 64.9% and 87.1% with the cutoff value of
      ADM/APB=0.739. Conclusion: The ADM/APB has certain clinical value for the
      differentiation of ALS and CSA.

PMID- 29325329
TI  - [Feasibility of using blood oxygen level-dependent magnetic resonance imaging to
      evaluate renal fibrosis of ureteral obstruction of rabbits].
AB  - Objective: To investigate the feasibility of blood oxygen level-dependent MR (MR
      BOLD) in assessing renal fibrosis of ureteral obstruction of rabbits. Methods:
      Forty healthy New Zealand rabbits were randomly divided into control group (n=8)
      and unilateral ureteral obstruction (UUO) group (n=32). The rabbits in the UUO
      group were subjected to unilateral ureteral obstruction of the left
      kidney.Coronal T(2) weighted imaging (T(2)WI) and axial BOLD examinations were
      performed before operation, 2, 4, 6 and 8 W after operation (each subgroup n=8).
      After the examinations, nephrectomy was performed for histologic evaluation.The
      T(2)(*) relaxation rate of the renal cortex (CR(2)(*)) , medulla (MR(2)(*)) and
      the same level of muscle(R(2)(*)(muscle)) were measured separately.The
      normalization of the cortex and medulla (sR(2)(*)), and the difference of
      sR(2)(*) between renal cortex and medulla before and post UUO (DeltasR(2)(*))
      were calculated.The differences of sR(2)(*) (sCR(2)(*), sMR(2)(*),
      sCR(2)(*)(control), sMR(2)(*)(control)) at each time point between control and
      UUO group were compared by using independent sample t test.The LSD test was used
      to compare the sR(2)(*) in the control with that in the UUO group.The
      DeltasCR(2)(*) and DeltasMR(2)(*) values of the subgroups at UUO 2, 4, 6 and 8 W
      were compared by independent sample t test. Results: The sR(2)(*) values of UUO
      group were all lower than those of control group (all P<0.05), while
      sR(2)(*)(control) and sR(2)(*) in UUO group before operation were not significant
      different (P>0.05). The sCR(2)(*) values of UUO 2, 4, 6 and 8 W were 0.32+/-0.01,
      0.37+/-0.01, 0.47+/-0.02 and 0.50+/-0.03.The sMR(2)(*) values were 0.39+/-0.02,
      0.48+/-0.02, 0.58+/-0.04 and 0.65+/-0.05.There were significant differences of
      sCR(2)(*)(between) UUO 2 W and 6 W, UUO 2 W and 8 W, UUO 4 W and 6 W, UUO 4 W and
      8 W (all P<0.01). There were significant differences of sMR(2)(*)(between) UUO 2
      W and 6 W, UUO 2 W and 8 W, UUO 4 W and 8 W (all P<0.01). No significant
      difference was founded between sCR(2)(*) and sMR(2)(*) at each time point in
      control group (P>0.05). The DeltasCR(2)(*) values of UUO 2, 4, 6 and 8 W were
      0.31+/-0.02, 0.20+/-0.02, 0.14+/-0.20, 0.09+/-0.04; the DeltasMR(2)(*) values
      were 0.51+/-0.05, 0.36+/-0.04, 0.28+/-0.05, 0.19+/-0.05. The DeltasCR(2)(*)
      values of UUO 2, 4 and 6 W were less than DeltasMR(2)(*) (P<0.05). There was no
      significant difference between DeltasCR(2)(*) and DeltasMR(2)(*) in UUO 8 W
      (P>0.05). Conclusions: The R(2)(*) change in medulla resulted from renal fibrosis
      is more significant than cortex.MR-BOLD can reflect the process of renal
      fibrosis.It's feasible and of great value to use renal MR-BOLD for the assessment
      of renal fibrosis induced by unilateral ureteral obstruction.

PMID- 29325331
TI  - [Pay attention to standardinzing classification fo spinal neural tube defects].

PMID- 29325330
TI  - [Effects of repetitive transcranial magnetic stimulation on upper limb motor
      function in patients with stroke: a meta analysis].
AB  - Objective: To perform a meta analysis of studies that investigated the effects of
      repetitive transcranial magnetic stimulation (rTMS) on upper limb motor function
      in patients with stroke. Methods: We searched for related articles published
      before October 2015 in MEDLINE(Pubmed) (January 1966 to October 2015), Cochrane
      Central Register of Controlled Trials (CENTRAL) (October 2015), EMBASE(SCOPUS)
      (January 1974 to October 2015), Chinese Biomedical Database (CBMDisc) (January
      1978 to October 2015), China National Knowledge Infrastructure (CNKI) (January
      1979 to October 2015) and Wanfang database(January 1989 to October 2015).
      Results: A total of nine studies with 289 patients were included in this
      analysis.The results showed that rTMS had a significant effect for ischemic
      stroke patients with upper limb motor disorder with SMD 0.43, 95%CI 0.19-0.67,
      P=0.000 4. Further subgroup analyses about high or low frequency rTMS
      demonstrated low frequency rTMS showed prominent effects for the stroke patients
      with SMD 0.50, 95%CI 0.14-0.85, P=0.007.Only 3 patients from the 9 studies
      included in this analysis reported adverse effects from rTMS. Conclusions: The
      meta analysis suggests that rTMS has a positive effect on motor recovery in
      patients with stroke, especially the low frequency rTMS may be more
      beneficial.The clinical application of rTMS in patients with stroke is relatively
      safe.Intermittent theta-burst stimulation might be a useful intervention.

PMID- 29325332
TI  - [Gender differences of REM related obstructive sleep apnea-hypopnea syndrome].
AB  - Objective: To explore the gender differences of rapid-eye-movement (REM) related
      obstructive sleep apnea-hypopnea syndrome (OSAHS). Methods: Consecutive patients
      with primary complaint of snoring from Sleep Medicine Center of West China
      Hospital between January 2016 and November 2016 were included in the study. All
      participants underwent one night polysomnography (PSG) and Epworth sleep scale
      (ESS) was estimated. The patients diagnosed with OSAHS were classified as REM
      related OSAHS (REM-OSAHS group) and non-rapid-eye-movement (NREM) related OSAHS
      (NREM-OSAHS group) based on the PSG parameters. And the gender differences of
      demographic and polysomnograpic characteristics in both groups were compared. The
      associations between apnea-hypopnea index (AHI) and body mass index (BMI), neck
      circumference and waist circumference among patients with OSAHS were explored by
      multiple linear regression analysis. Results: A total of 1 258 patients were
      diagnosed with OSAHS. There were 997 (79.3%) male and 261 (20.7%) female among
      these patients, the mean age was (46.4+/-12.0) years old and mean BMI was (26.6+/
      3.4) kg/m(2). There were 236 patients (18.8%) classified into REM-OSAHS group,
      and 1 022 patients (81.2%) classified into NREM-OSAHS group; the proportion of
      REM-OSAHS in female was significantly higher than that in male (34.1% vs 14.7%,
      P<0.001). After controlling for age, drinking, smoking, hypnotics, coffee, strong
      tea and sleep related parameters, in NREM-OSAHS group, AHI was positively
      correlated with BMI, neck circumference and waist circumference (P<0.001) both in
      male and female. In REM-OSAHS group, AHI was positively correlated with BMI, neck
      circumference and waist circumference in female (P<0.05), but only significantly
      correlated with BMI and waist circumference in male (P<0.05). Conclusions: REM
      OSAHS is commonly seen in female OSAHS patients. Evaluation of the influences of
      anthropometric data on the severity of REM-OSAHS should consider the impact of
      gender.

PMID- 29325333
TI  - [Biomechanical effects on adjacent segments of different growing-rod fixation in
      early onset scoliosis].
AB  - Objective: To analyse the biomechanical effects on adjacent segments of different
      growing-rod (GR) fixation in early onset scoliosis through a finite element
      analysis method. Methods: A severe early-onset scoliosis patient was selected and
      the pre-operation and post-GR-operation (Upper instrumented levels: T(4), T(5).
      Lower instrumented levels: L(3), L(4)) whole spine 3-dimentional CT scan data
      were collected to build the finite models. Based on the different models,
      biomechanical differences on adjacent segments were analysed. Results: The stress
      on the adjacent structures decreased after the GR surgery compared with the pre
      operation. Compared with the single GR, stress on T(3) vertebrae decreased by
      6.2%, stress on T(3/4) disc decreased by 6.7%, stress on T(3/4) ligament
      decreased by 27.7%, stress on T(6) vertebrae decreased by 16.9%, stress on T(5/6)
      disc decreased by 1.2%, stress on T(5/6) ligament decreased by 40.4%, stress on
      L(2) vertebrae decreased by 32.6%, stress on L(2/3) disc decreased by 30%, stress
      on L(2/3) ligament decreased by 15.6%, stress on L(5) vertebrae decreased by
      1.2%, stress on L(4/5) disc decreased by 15.7%, stress on L(4/5) ligament
      decreased by 100.0% in dual GR structure. The application of hook (s) on the
      upper instrumented vertebrae (s) decreased the stress on the cranial adjacent
      segment. Stress on T(3) vertebrae decreased by 2.8% and 2.2%, stress on T(3/4)
      disc decreased by 2.4% and 1.5%, stress on T(3/4) ligament decreased by 3.6% and
      5.7% in single GR and dual GR models separately when the hook (s) were utilized.
      In the meanwhile, the stress on the adjacent segment was more concentrated in the
      single GR model. Conclusion: Dual-rod growing-rod and the application of hook (s)
      on the upper instrumented vertebrae could reduce the stress on the adjacent
      segments more effectively in patients with early onset scoliosis.

PMID- 29325334
TI  - [Analysis on the novel compound heterozygous mutation FXI of a patient with
      hereditary factor XI deficiency].
AB  - Objective: To investigate the clinical phenotype and genotype characteristics of
      a Chinese hereditary factor XI deficiency pedigree. Methods: The activated
      partial thromboplastin time (APTT), prothrombin time (PT), FXI activity (FXI: C)
      were measured by clotting method using automatic coagulation analyzer. The FXI
      antigen (FXI: Ag) was assayed by enzyme-linked immunosorbent assay (ELISA).
      Fifteen exons of F11 from the proband and his pedigree members were amplified by
      polymerase chain reaction (PCR), then sequenced. Pymol software was used to
      analyze the novel mutations. Results: APTT, FXI: C and FXI: Ag of proband was
      74.2 s, 4.0% and 2.9%, respectively. For his older sister, APTT, FXI: C and FXI:
      Ag was 67.1 s, 3.0% and 1.8%, respectively. APTT, FXI: C and FXI: Ag of healthy
      controls were 34.5 s, 100.0% and 100.0%. FXI: C of proband's father, mother and
      brother were 72.0%, 62.0%, and 78.0%, respectively. FXI: Ag of them were 50.0%,
      43.0%, and 51.8%, respectively. The other coagulant parameters of the proband and
      his pedigree were all in the normal range. Sequence analysis showed two
      heterozygous gene mutations in F11 of the proband and his older sister. One was a
      deletion of T at nucleotide 1 491 in exon 12, resulting in a frameshift. A
      substitution of leucine 465 by tryptophan and a terminal coden after 7 amino
      acid: F11NM_13142c.1491delT (p.Leu465Trp.fs*7). The other was a G to A
      substitution at nucleotide 1 815 in exon 15, resulting in a substitution of
      glycine 573 by aspartic acid: F11 NM_13142c.1815G>A (p.Gly573Asp).
      F11NM_13142c.1491delT (p.Leu465Trp.fs*7) heterozygotes were found both in the
      proband's father and his brother while p. Gly573Asp heterozygote was only found
      in his mother. F11 of the proband's uncle was wild. Conclusion: The novel
      compound heterozygous mutations of F11NM_13142c.1491delT (p.Leu465Trp.fs*7) and
      F11 NM_13142 c. 1815G>A (p.Gly573Asp) are responsible for FXI deficiency to the
      proband, which induced the decrease of FXI: C and FXI: Ag.

PMID- 29325335
TI  - [Association between serum adipocyte fatty acid binding protein level and insulin
      resistance in patients with OSAS].
AB  - Objective: To investigate the association between serum adipocyte fatty acid
      binding protein (A-FABP) level and insulin resistance in patients with
      obstructive sleep apnea syndromes (OSAS). Methods: Eighty patients with snoring
      were monitored by overnight polysomnography (PSG) from September 2015 to July
      2017, and there were 59 males and 21 females, aged from 22 to 77 years old (mean
      age 47+/-14 years old). Based on the apnea-hypopnea index (AHI), these patients
      were divided into three groups: primary snoring group (AHI<5/h, n=19), mild
      moderate OSAS groups (5/h<=AHI<=30/h, n=23) and severe OSAS groups (AHI>30/h,
      n=38). The levels of A-FABP, the fasting plasma glucose (FPG), fasting insulin
      (FINS) and insulin resistance index (IRI) were compared between the primary
      snoring group and OSAS patients with different severities, and the correlations
      between serum A-FABP and IRI as well as PSG parameters were further evaluated
      using partial correlation analysis. Results: Compared with the primary snoring
      group [(15.6+/-3.5) MUg/L] and mild-moderate group [(17.4+/-4.3) MUg/L], there
      was a significant increase of the serum A-FABP level in the severe OSAS group
      [(21.4+/-4.6) MUg/L](P=0.001, P=0.025). Additionally, after adjustment for BMI
      and age, serum A-FABP level showed significant positive correlations with FINS
      and IRI (r=0.478, P<0.001; r=0.356, P=0.035); serum A-FABP level was positively
      correlated with AHI and the arterial oxygen saturation (SaO(2)) < 90% time ratio
      in night (TS90%) (r=0.251, P=0.041 and r=0.271, P=0.035). Nevertheless, serum A
      FABP level showed significant negative correlation with the lowest SaO(2) and the
      mean SaO(2) (r=-0.244, P=0.038 and r=-0.280, P=0.018). Conclusion: Insulin
      resistance and the increased level of serum A-FABP are common in OSAS patients,
      the level of serum A-FABP is significantly correlated with insulin resistance and
      nocturnal intermittent hypoxia, both of which suggest that A-FABP plays a
      potential role in insulin resistance in patients with OSAS.

PMID- 29325336
TI  - [Dose-response relationship of ropivacaine for epidural block in early herpes
      zoster guided by CT].
AB  - Objective: To determine the dose-response relationship of ropivacaine for
      epidural block in early herpes zoster by CT guided. Methods: From January 2015 to
      February 2017, according to the principle of completely random digital table, 80
      patients with early herpes zoster who were prepared for epidural block were
      divided into 4 groups(each group 20 patients): in group A the concentration of
      ropivacaine was 0.08%, in group B was 0.10%, in group C was 0.12% and in group D
      was 0.14%.Under CT guidance, epidural puncture was performed in the relevant
      section, mixing liquid 5.0 ml (with 10% iodohydrin)were injected into epidural
      gap.CT scan showed that the mixing liquid covered the relevant spinal nerve
      segmental.The numeric rating scale(NRS) values before treatment and at 30
      minutes, the incidence of adverse reactions were recorded, and the treatment were
      evaluated. The response to ropivacaine for epidural block in early herpes zoster
      was defined as positive when the NRS values was less than or equal to one.The
      ED(50), ED(95) and 95% confidence interval (CI) of ropivacaine for epidural block
      in early herpes zoster guided by CT were calculated by probit analysis. Results:
      The NRS values before treatment were 5.00(4.00, 6.00), 5.00(4.25, 6.00),
      5.50(5.00, 6.00) and 5.00(4.00, 6.00), the difference was no significant(Z=2.576,
      P=0.462). The NRS values at 30 minutes decreased and the effective rate of the
      treatment increased(chi(2)=8.371, P=0.004), following ropivacaine dose gradient
      increasing, they were 1.50(1.00, 2.00), 1.00(1.00, 2.00), 0.50(0.00, 1.00) and
      0.00(0.00, 1.00), the difference was statistically significant (Z=17.421,
      P=0.001). There was one case in group C and four cases in group D were
      hypoesthesia, others were no significant adverse reactions occurred. The ED(50)
      and ED(95) (95%CI) of ropivacaine for epidural block in early herpes zoster
      guided by CT were 0.078%(0.015%-0.095%)and 0.157%(0.133%-0.271%), respectively.
      Conclusion: Ropivacaine for epidural block in early herpes zoster guided by CT is
      effective for neuropathic pain, with no significant adverse reactions.

PMID- 29325337
TI  - [The application of combining low dose naloxone with ropivacaine in
      supraclavicular brachial plexus block].
AB  - Objective: To observe the effect of low dose naloxone combinewith ropivacaine for
      supraclavicular brachial plexus block. Methods: Seventy patients undergoing
      elective upper limb surgery were randomly divided into two groups, ropivacaine
      group (Group R, n=35) and naloxone group (Group N, n=35). An ultrasound guided
      technique was used in both two groups.The onset and duration time of sensory and
      motor blockade, visual analog score(VAS)of 3, 6, 12, 18, 24 h postoperatively,
      time of first request fordezocine, total amount of dezocine needed, incidence of
      nausea and vomiting postoperatively(PONV) and patients' satisfaction score for
      analgesia in 24 h after surgery were measured.At the same time, blood samples
      were taken before anesthesia, 6 h, 24 h after operation for inspecting the
      concentration of beta-endorphin(beta-EP)in plasma. Results: The duration of
      sensory and motor blockade, time of first request for dezocine in Group N were
      736.0(713.5, 836.5), 514.5(491.3, 572.8), 708.5(683.2, 877.0)min, which were all
      prolonged compared to Group R(522.0(469.5, 606.5), 401.0(370.0, 458.5),
      570.0(435.0, 618.5)min)(Z=-6.844, -6.758, -6.700, all P<0.01). The 6, 12, 18 h
      postoperatively VAS of Group N were 0, 5.0(3.0, 5.8), 5.0(5.0, 6.0)point. Among
      which the 6, 12 h postoperatively VAS of Group N were lower than that of Group
      R(1.0(1.0, 3.5), 6.0(6.0, 7.0)point)(Z=-6.596, -4.864, all P<0.01), while the 18
      h postoperatively VAS was higher than that of Group R (5.0(4.0, 5.0)point)(Z=
      2.603, P<0.01). Total amount of dezocine needed in Group N in 24 h after surgery
      was 7.5(5.0, 10.0)mg, which was lower than that of Group R(10.0(10.0, 15.0)mg)(Z=
      3.449, P<0.01). The incidence of PONV after surgery in Group N was 21.9%, which
      was lower than that of Group R(45.5%)(chi(2)=4.034, P<0.05). Ptients'
      satisfaction score for analgesia in 24 h after surgery in Group N was 8.0(7.0,
      8.0)point, which was higher than that of Group R(7.0(6.0, 7.0)point)(Z=-3.509,
      P<0.01). At 6 h postoperatively , the concentration of plasma beta-EP in Group N
      was(113.34+/-12.36)MUg/L, lower than that of Group R((147.14+/-11.65)MUg/L)(t=
      7.694, P<0.01). Conclusion: Low dose naloxone combine with ropivacaine for
      supraclavicular brachial plexus block, prolong the duration of sensory and motor
      blockade without affecting the onset time.

PMID- 29325338
TI  - [Supplementation with high-dose L-carnitine on hemodialysis tolerance in uremic
      patients with severe heart diseases].
AB  - Objective: To investigate the effect of intravenous supplementation with high
      dose L-carnitinen on hemodialysis tolerance in uremic patients with severe heart
      disease (ischemic heart disease, congestive heart disease and arrhythmia).
      Methods: Between March 2012 and March 2017, 5 gram L-carnitine was given after
      the completion of each hemodialysis treatment (3-4 times a week) over a period of
      two weeks in 29 maintenance hemodialysis patients with severe heart diseases
      manifested by frequently symptomatic hypotension, chest tightness, wheezing,
      palpitation, chest pain and other symptoms during hemodialysis. The hemodialysis
      duration, heart functional classification (New York Heart Association Functional
      Classification, NYHA ), blood pressure and arrhythmia were analyzed before and
      after the treatment. Results: The duration of hemodialysis was significantly
      prolonged after treatment [from 2.0-3.5 (2.6+/-0.4)h to 3.0-4.0 (3.8+/-0.4) h,
      t=10.66, P<0.01]. Cardiac function was improved (Z=-4.74, P<0.01). The
      hypotension and arrhythmia during dialysis was improved. Conclusion: High-dose of
      intravenous L-carnitine supplementation can improve hemodialysis tolerance and
      the symptoms of heart failure, arrhythmia, ischemic cardiac disease in
      hemodialysis patients with severe heart diseases.

PMID- 29325339
TI  - [Risk factors and impacts on prognosis of ultrasound lung comets in patients
      undergoing hemodialysis].
AB  - Objective: To investigate the risk factors of ultrasound lung comets and its
      impact on the survivals of patients undergoing hemodialysis. Methods: One hundred
      and forty-two patients on hemodialysis (Male 76, female 66) were divided into
      three groups according to the score of lung comets (mild: <=14 comets; moderate:
      15 to 30 comets; severe: >30 comets). Seventy-two healthy subjects examined by
      lung ultrasound serve as a control. Pulmonary artery systolic pressure and left
      ventricular ejection fraction (LVEF) were assessed by Doppler ultrasonography.
      High-sensitivity C-reactive protein (hsCRP) and tumor necrosis factor (TNF)-alpha
      were measured by the automatic analyzer and enzyme-linked immunosorbent assay.
      Results: With the increasing age of the patients, lung comets scores increased
      (P<0.05). There were significant differences in TNF-alpha (P<0.05), interdialytic
      weight gain (IDWG) (P<0.05), pulmonary artery systolic pressure and LVEF (P<0.05)
      among three groups. In multivariate linear regression, the lung comets score was
      positively related to multiple clinical variables including New York Heart
      Association (NYHA) classification (P=0.023), hsCRP (P=0.042), TNF-alpha
      (P<0.001), IDWG (P=0.031), and pulmonary artery systolic pressure (P<0.001). In
      the multivariate Cox proportional hazards models, lung comets score was
      independent risk factor for death (P=0.001). In Kaplan-Meier survival analysis,
      the risk of all-cause mortality increased in parallel with lung comets score, and
      patients with lung comets score (>30 comets) were at highest risk of death among
      all three groups (log-rank test chi(2)=12.73, P=0.001). Conclusion: Lung comets
      is associated with inflammation, pulmonary artery systolic pressure/volume
      overload and heart function. Lung comets score represents the alterations of
      heart function and it may serve as a powerful predictor of all-cause mortality
      for hemodialysis patients.

PMID- 29325340
TI  - [Association between small dense low-density lipoprotein cholesterol and carotid
      atherosclerosis].
AB  - Objective: To explore the association between small dense low-density lipoprotein
      cholesterol (sdLDL-C) and carotid atherosclerosis. Methods: 1 578 subjects were
      enrolled in an annual health check-up program in aerospace center hospital from
      2016 to 2017, and these patients were divided into 471 cases (men 343 and women
      128) with carotid atherosclerosis (subjects with increased carotid artery intima
      media thickness or carotid atherosclerosis plaque) and 1 107 cases (men 567 and
      women 540) with non- carotid atherosclerosis according to ultrasonography. Serum
      sdLDL-C levels were measured by peroxidase assay. Results: Serum sdLDL-C was
      significantly higher in carotid atherosclerosis group (1.11+/-0.44) mmol/L than
      that in non-carotid group (0.88+/-0.40) mmol/L, with significant difference
      (t=9.856, P<0.001). Stratified by quartiles of sdLDL-C (Q1-Q4), the prevalence of
      carotid atherosclerosis was significantly increased trend along with increased
      sdLDL-C levels (P<0.001). In multivariate Logistic regression analysis, after
      adjustment for age, sex and other traditional atherosclerosis risk factors,
      comparing Q4 with Q1, the odd ratio of prevalence of carotid atherosclerosis was
      5.164, and 95% confidence interval(CI) was 2.833-9.413. While the sdLDL-C
      threshold was 0.727 mmol/L as the optimal cut-off point, the clinical sensitivity
      and specificity of sdLDL-C for screening carotid atherosclerosis were 80.5% and
      41.4%, respectively. Conclusion: Serum sdLDL-C was an independent risk factor of
      carotid atherosclerosis. sdLDL-C may be a potentially useful risk marker in early
      screening for carotid atherosclerosis.

PMID- 29325341
TI  - [Morphological characteristics and phenotypic analysis of multiple morphological
      abnormalities in sperm flagella].
AB  - Objective: To analyze the sperm morphological characteristics of multiple
      morphological abnormalities of the sperm flagella (MMAF), and to analyze their
      common features and subtypes. Methods: Twenty-eight patients with abnormal
      morphology of flagella were analyzed by semen analysis. The morphological
      characteristics were analyzed by scanning electron microscopy and transmission
      electron microscopy. Histological observation of one case of testicular tissue
      was performed. Results: Of the 28 patients, only 13 patients (46.4%) had motile
      spermatozoa, 12 of which had a sperm motility rate of <10% and a sperm survival
      rate of 9.0%-80.0%. Under light and scanning electron microscope, sperm with
      absent, short, coiled, bent and irregular width flagella or their combinations
      were observed. Transmission electron microscopy showed structural abnormalities
      of sperm fibrous sheath, mitochondrial sheath. Loss rate of central microtubule
      was 41.4%-84.6%. The semen of the 2 patients with the absence or presence of the
      kinetic protein arm and both the inner and lateral motilin arms missing had no
      motile spermatozoa. There was no statistically significant difference in the
      proportion of flagellar malformations between the two groups of patients (without
      motile sperm vs with motile spermatozoa). Conclusion: MMAF is a kind of sperm
      flagella specific abnormalities. Initially diagnosis can be carried out using
      light microscopy. Clear diagnosis could be conduct using transmission electron
      microscopy, and the central microtubule loss of the sperm could be seen as the
      main feature of the flagella abnormalities. Through the morphological analysis
      and research, MMAF could be precisely classified, which provide a strong basis
      for the diagnosis.

PMID- 29325342
TI  - [Computer Aided Diagnosis system of breast ultrasound based on support vector
      machine: a clinical analysis].
AB  - Objective: To investigate the value of based on support vector machine (SVM)
      breast ultrasonography technology of Computer-Assisted diagnosis (CAD) for
      differential diagnosis of benign and malignant breast masses. Methods: Total of
      143 patients who had 151 breast masses were collected in Fujian Maternity and
      Children Health Hospital or The Fist Affiliated Hospital of Fujian Medical
      University from June 2014 to December 2015. Based on pathological results as the
      gold standard, the diagnostic efficiency of CAD and ultrasonography were
      compared. Results: The sensitivity, specificity, accuracy, positive predictive
      value and negative predictive value of ultrasonography were 80.1%, 71.0%, 76.8%,
      80.0% and 72.1%, respectively. And the sensitivity, specificity, accuracy,
      positive predictive value and negative predictive value of CAD were 96.6%, 90.3%,
      94.0%, 93.5% and 94.9%, respectively. The specificity, accuracy, positive
      predictive value and negative predictive of CAD technology were significantly
      higher than those of ultrasonography (P<0.05). The area under the receiver
      operator characteristic curve of ultrasonography and CAD were 0.759 and 0.935
      respectively, with significant difference (P<0.05). Conclusions: CAD has a higher
      specificity and accuracy rate than ultrasonography in the diagnosis of breast
      masses. It could help to differentiate benign from malignant breast masses.

PMID- 29325343
TI  - [Expression and significance of autophagy in rabbit model of tracheal stenosis].
AB  - Objective: To investigate the expression and significance of autophagy in rabbit
      model of tracheal stenosis. Methods: A total of 18 rabbits were equally divided
      into 3 groups (blank control group, saline group, erythromycin group) in
      accordance with the random number table. After rabbit model of tracheal stenosis
      was established, no treatment was done with blank control group. Saline group was
      atomized with saline (0.54 mg/kg, 2 times/day), and erythromycin group was fed on
      erythromycin (7.5 mg/kg, 2 times/day) for 7 days before and 10 days after the
      operation. On the eleventh day, rabbits were executed, and their trachea were
      collected. The proportion of collagen fiber area of tracheal lamina propria (LP)
      and epithelium (EP) was assessed by Masson staining. The mRNA of autophagy
      associated gene-3 (ATG3) and autophagy associated gene-5 (ATG5) of tracheal
      mucosa were assessed by Real-Time Polymerase Chain Reaction (RT-PCR). The protein
      of microtubule-associated protein 1 light chain beta(3) (LC3B), ATG3 and ATG5
      were assessed by Western blot. Results: The proportion of collagen fiber area of
      tracheal LP and EP of blank control group was (6.79+/-0.67)%, saline group was
      (40.55+/-5.40)%, erythromycin group was (27.48+/-0.43)%. The differences between
      any two groups was all statistically significant (all P<0.01). The relative value
      of ATG3 mRNA and ATG5 mRNA in saline group were significantly lower than blank
      control group (all P<0.01). Those value in erythromycin group were significantly
      higher than the saline group (all P<0.01). The protein levels of LC3B-II/I, ATG3
      and ATG5 in saline group were significantly lower than blank control group (all
      P<0.01). After low dose of erythromycin intervention, all the protein levels were
      significantly higher than the saline group (all P<0.01). Conclusions: The
      expression of autophagy is decreased in rabbit model of trachea stenosis. Low
      dose of erythromycin could increase the expression of autophagy and at the same
      time alleviate the degree of fibrosis of the tracheal mucosa. Autophagy may
      alleviate tracheal fibrosis through up-regulating its expression level and play a
      protective role.

PMID- 29325344
TI  - [Experimental observation of hyperbaric oxygen combined with radioactive seed
      implantation in the treatment of nude mice bearing esophageal squamous cell
      carcinoma].
AB  - Objective: To investigate the effect and mechanism of hyperbaric oxygen combined
      with radioactive seed implantation in the treatment of esophageal squamous cell
      carcinoma. Methods: Subcutaneous tumor model of esophageal squamous cell
      carcinoma using TE-8 cells was established. Tumor bearing Balb/c(nu/nu) mice (60
      mice) were divided into four groups, Cont group that treated with normal oxygen
      level, HBO group that treated with hyperbaric oxygen, RSI group that treated with
      radioactive seed implantation, and HBO+ RSI group that treated with hyperbaric
      oxygen combined with radioactive seed implantation. Tumor volume ratio and mean
      survival time of tumor bearing mice were observed. Pathological changes of tumor
      tissue after treatment were observed by hematoxylin eosin (HE) staining. Enzyme
      linked immunosorbent assay kit was used to detect oxidative stress. Apoptosis
      related proteins were detected by Western blot. Results: After treatment, the
      tumor volume ratio of HBO+ RSI group was 3.51+/-0.80 and was significantly lower
      than that of Cont group, HBO group, and RSI group (P<0.05). The mean survival
      time of HBO+ RSI group tumor bearing mice was 62 d and was significantly longer
      than that in Cont group, HBO group, and RSI group (P<0.05). HE staining showed
      that the pathological changes of tumor tissues were most obvious in HBO+ RSI
      group. After treatment, the MDA and Bax levels in nude mice of HBO+ RSI group
      were significantly higher than those in Cont group, HBO group and RSI group, but
      the levels of GSH, SOD and Bcl-2 were significantly lower than those of Cont
      group, HBO group and RSI group (P<0.05). Conclusion: Hyperbaric oxygen combined
      with radioactive seed implantation could slow tumor growth and increase survival
      time of tumor bearing mice. The possible mechanism is that hyperbaric oxygen
      combined with radioactive seed implantation can improve the oxidative stress
      response and the expression of apoptosis protein in tumor bearing nude mice.

PMID- 29325345
TI  - [Important issues need to be emphasized in the diagnosis and treatment of
      pancreatic cystic neoplasms].
AB  - The patients of pancreatic cystic neoplasms diagnosed and treated are increasing
      over the past decade. Recent and long-tern risk and benefit should be well
      balanced when considering treatment, follow the principle of patient-benefit. For
      low malignancy potential neoplasm like serous cystic tumor or branch duct
      intraductal papillary mucinous neoplasm, surgical indication should be reserved
      to those with obvious malignant potential.Decreasing perioperative mortality and
      morbidity should be emphasized. Comprehensive studies are needed to validate the
      efficacy of new diagnostic and treatment technique before applied to clinical.
      Oncological outcome could not be compromised in order to achieve minimal invasive
      effects.

PMID- 29325347
TI  - [Opportunities and challenges in the development of pancreatic surgery].
AB  - Pancreatic surgery is characteristic of various and complicated diseases and
      difficult surgeries. Pancreatic surgeons are required to grasp the new concept,
      apply new techniques and comprehend the study trends of pancreatic diseases.
      Otherwise, pancreatic surgeons should fully realize the opportunities and
      challenges resulted from application of new concept and techniques as well as
      learning new concept and techniques. Meanwhile, they should grasp the updating
      guidelines and research progress, intensively promote the development of
      prospective multicenter research involved in multidisciplinary team, and then
      promote the rapid development of pancreas surgery in China.

PMID- 29325346
TI  - [Evidence-based guideline for the management of acute subaxial cervical spine
      injury].
AB  - In order to provide the clinical guidelines of acute subaxial cervical spine
      injury for the Chinese orthopedic surgeons, the Spine Trauma Group of Chinese
      Association of Orthopedic Surgeons compiled this guidelines.The guidelines apply
      to adult patients with acute (less than 3 weeks) subaxial cervical spine and/(or)
      spinal cord or nerve root injuries. The Study Group wrote the guidelines by
      setting up questions, determining search words, screening literatures according
      to inclusion and exclusion criteria, analyzing the included literatures,
      confirming evidence levels and then providing recommendations. The guidelines
      include 141 literatures, 27 Chinese articles and 114 English articles. The
      guidelines set up 18 questions divided into 4 sections: pre-hospital care,
      diagnosis and evaluation, treatment and prevention of complications, which
      include 39 recommendations.

PMID- 29325348
TI  - [Multidisciplinary team building in enhanced recovery after surgery].
AB  - There has been 10 years to explore the road in line with China's actual enhanced
      recovery after surgery(ERAS) since Academician Li Jieshou introduced the view of
      ERAS into China. ERAS has been widely carried out in the field of surgery, and
      gradually formed with Chinese characteristics of ERAS clinical pathway.The
      clinical implementation of ERAS relies on the effective integration of a series
      of perioperative methods, and any single technique or method can't completely
      reduce the perioperative physiological and psychological traumatic stress of the
      patient, so as to achieve the patient's rapid rehabilitation patient-centered
      multidisciplinary team(MDT)collaboration is an inevitable trend in ERAS
      development. On the basis of drawing lessons from foreign experience, the
      establishment of ERAS-MDT model in line with China's national conditions is a new
      subject that needs to be studied at present. The construction of ERAS-MDT might
      promote the development of new ERAS services, new technologies, and ultimately
      promote the improvement of surgical treatment, and bring the greatest clinical
      benefit to the society and patients.

PMID- 29325349
TI  - [Introduction and interpretation of guidelines on thromboprophylaxis in the
      perioperative period of urological surgery].
AB  - Venous thromboembolism had drawn great attention of global experts, as it is the
      third leading cause of cardiovascular-associated death, ranking after coronary
      heart disease and stroke. Numerous health care organizations had introduced
      guidelines for thromboprophylaxis during the perioperative period in their own
      fields. The paper reviewed the available guidelines pertaining to urological
      surgery from America Urological Association, American College of Chest Physicians
      and European Association of Urology. Compared with the first two guidelines, the
      European Association of Urology guideline is a milestone which recommended the
      most detailed prophylactic measures for the procedure-specific and patient
      specific according to the evidence-based medicine. Meanwhile, there was still no
      reliable evidence in fields of the effect of new oral anticoagulants in urology,
      needing further study. Although they were similar in patient management and
      prophylaxis principles, there are still some differences in risk factors,
      assessments, and recommendations of prophylactic measures. In this context, we
      planed to summarize the highlights and compare the differences of three
      guidelines addressing the use of thromboprophylaxis in urology, in order to
      provide reference for Chinese urologists to select the best prevention strategies
      for patients in the perioperative period.

PMID- 29325350
TI  - [The current status of diagnosis and treatment of pancreatic cystic neoplasm in
      China: a report of 2 251 cases].
AB  - Objective: To analyze the current status of diagnosis and treatment of pancreatic
      cystic neoplasm(PCN)in China. Methods: Clinical data of 2 251 PCN patients who
      underwent surgical resection from January 2006 to December 2016 in 16
      institutions was retrospectively analyzed.Excel database was created which
      covered 132 fields of 7 fields: general information of patients, imaging
      findings, preoperative blood biochemical indexes, tumor markers, surgical related
      data, postoperative complications and pathology. Results: Of the 2 251 patients,
      the male to female ratio was 1.0 to 2.4, and the mean age at diagnosis was 47.5
      years(range, 8-89 years). Solid pseudo-papillary tumor(SPT), Serouscystic
      neoplasm(SCN), Intraductal papillary mucinous neoplasm(IPMN), mucinous cystic
      neoplasm(MCN) were 713 cases, 678 cases, 495 cases, 365 cases, respectively; and
      the malignant transformation rate was 12.3%, 0.6%, 32.1%, 10.4%, respectively.
      Carcinoembryonic antigen, CA19-9, CA125 were significantly increased in the
      malignant group.The incidence of postoperative complications in SCN was the
      highest.Preoperative CT scan was the most common method in China.The
      characteristics of IPMN included atrophy of pancreas body and tail, dilatation of
      the main pancreatic duct, and pancreatitis, and these characteristics were three
      to six times more than other 3 kinds of PCN.The correct rate of preoperative
      diagnosis to subtype was 33.0%. Conclusions: SPT is the most common tumor in all
      PCN in China.One of the key research directions is to improve the accuracy of
      subtype diagnosis to avoid unnecessary surgery.

PMID- 29325351
TI  - [Analysis of risk factors and outcomes for delayed gastric emptying following
      pancreaticoduodenectomy: a single center experience of 492 cases].
AB  - Objective: To evaluate risk factors for delayed gastric emptying(DGE)following
      pancreaticoduodenectomy(PD). Methods: There were 492 consecutive patients who
      underwent PD in Pancreas Center, the First Affiliated Hospital with Nanjing
      Medical University between January 2012 and December 2014 were identified from a
      prospective database.There were 315 male and 177 female patients with a median
      age of 60.5 years.Univariate and multivariate analyses were performed to
      investigate the independent risk factors for clinically relevant DGE(CR-DGE).
      Results: The overall incidence of DGE was 29.5%, with Grade B and C occurring at
      4.3% and 5.9%, respectively.In multivariate analysis, pancreatic duct diameter
      less than 3 mm(OR=1.888, P=0.042), pylorus-preserving
      pancreaticoduodenectomy(OR=2.627, P=0.005) and clinically relevant postoperative
      pancreatic fistula(OR=2.740, P=0.007) were independently associated with CR
      DGE.Other main complications such as postoperative pancreatic fistula,
      pyoperitoneum, intraabdominal infection were also associated with the severity of
      DGE(chi(2)=21.360, 14.422, 14.378; P=0.011, 0.002, 0.002). DGE patients had a
      significantly prolonged postoperative length of stay(31(24-41)d vs. 13(11-17)d)
      and increased medical cost((122 367.5+/-66 068.3)yuan vs. (78 200.7+/-27
      043.9)yuan)(both P<0.01). Conclusions: Small pancreatic duct, underwent pylorus
      preserving pancreaticoduodenectomy and suffered postoperative pancreatic fistula
      might indicate a high risk of CR-DGE.

PMID- 29325352
TI  - [Clinical application of combined hepatic artery resection and reconstruction in
      surgical treatment for hilar cholangiocarcinoma].
AB  - Objective: To clarify whether the surgical treatment for hilar cholangiocarcinoma
      combined with artery reconstruction is optimistic to the patients with hilar
      cholangiocarcinoma with hepatic artery invasion. Methods: There were 384 patients
      who received treatment in the First Affiliated Hospital to Army Medical
      University from January 2008 to January 2016 analyzed retrospectively. There were
      27 patients underwent palliative operation, 245 patients underwent radical
      operation, radical resection account for 63.8%. Patients were divided into four
      groups according to different operation method: routine radical resection
      group(n=174), portal vein reconstruction group (n=47), hepatic artery
      reconstruction group (n=24), palliative group(n=27). General information of
      patients who underwent radical operation treatment was analyzed by chi-square
      test and analysis of variance. The period of operation time, blood loss, the
      length of hospital stay and hospitalization expenses of the radical operation
      patients were analyzed by one-way ANOVA. Comparison among groups was analyzed by
      LSD-t test. Results: The follow-up ended up in June first, 2016. Each of patients
      followed for 6 to 60 months, the median follow-up period was 24 months. 1-, 3-,
      and 5-year survival rates were 81.3%, 44.9% and 13.5% of routine radical
      operation group, and were 83.0%, 44.7% and 15.1% of portal vein reconstruction
      group, and were 70.8%, 27.7% and 6.9% of hepatic artery reconstruction group,
      respectively. And 1-, 3-, and 5-year survival rates of hepatic artery
      reconstruction group was lower than routine radical group and portal vein
      reconstruction group significantly (P<0.05). However, the rate of postoperative
      complications of the hepatic artery reconstruction group and the routine radical
      operation group and the portal vein reconstruction group were 62.5%(15/24),
      55.3%(96/174) and 51.5%(24/47), respectively. There was no significant difference
      among them (P>0.05). The data shows that the ratio of lymphatic metastasis in
      hepatic artery reconstruction group (70.8%) is much higher than them in routine
      radical operation group (20.1%) and portal vein reconstruction group (19.1%)
      significantly (P<0.05). The presented data also indicate that hepatic artery
      resection prolongs survival time comparing with patients undergoing palliative
      therapy for hilar cholangiocarcinoma. Cox regression analysis indicate that
      hepatic artery resection and reconstruction is a protective factor compare with
      palliative therapy (RR=0.38, 95%CI: 0.22-0.67). The significant reason for
      shorter survival time is a positive correlation between hepatic artery invasion
      and lymph node metastasis. Conclusion: Hepatic artery resection and
      reconstruction has beneficial impact on oncologic long-term outcome in patients
      with advanced stage hilar cholangiocarcinoma.

PMID- 29325353
TI  - [Comparison of the short-term and long-term outcome between robotic gastrectomy
      and laparoscopic gastrectomy: a propensity score matching analysis].
AB  - Objective: To compare the short-term and long-term outcome between robotic
      gastrectomy and laparoscopic gastrectomy. Methods: The clinical data of 517
      patients who had received robotic gastectomy and laparoscopic gastrectomy between
      December 2011 and December 2013 at Department of General Surgery, Chinese
      People's Liberation Army General Hospital was collected. After propensity score
      matching, 70 patients in robotic gastectomy and 70 patients in laparoscopic
      gastectomy were identified. Perioperative outcome and overall survival were
      compared between the two groups using t test, chi(2) test, Kaplan-Meier curve and
      Log-rank test, respectively. Prognosis factors were analyzed by Cox's
      proportional hazards regression. Results: There were comparable baseline
      characteristics between patients in robotic group (RG) and those in laparoscopic
      group (LG). The conversion rate for RG and LG were 5.7% and 4.3% respectively
      (P=1.000). Compared with LG, RG had similar lymph node retrieval (25.5+/-7.2 vs.
      24.5+/-8.3, t=0.770, P=0.443) and less blood loss ((147.0+/-96.8) ml vs. (188.0+/
      111.2) ml, t=-2.326, P=0.021). There were also similar complications
      (chi(2)=0.233, P=0.629) and severity of complications (W=70.500, P=0.053).
      Although there tended to be early mobility, early flatus and less hospital stay
      for patients in RG group, the difference between RG and LG was not statistically
      significant. The 3-year survival rate was 72.9% and 60.0% for patients in RG and
      patients in LG (P=0.578). Multivariable analysis revealed gender (HR=2.529, 95%
      CI: 1.042 to 6.140, P=0.040), neoadjuvant chemotherapy (HR=0.272, 95% CI: 0.104
      to 0.710, P=0.008) and vascular invasion (HR=2.135, 95% CI: 1.027 to 4.438,
      P=0.042) were independent prognostic factors. Conclusion: Compared with
      laparoscopic gastrectomy, robotic gastectomy could achieve similar short-term and
      long-term outcomes.

PMID- 29325354
TI  - [Excision of giant desmoid in the abdominal wall, method of abdominal wall
      reconstruction, and follow-up of long-termed effect].
AB  - Objective: To explore the ideal procedure of excision and repair for giant
      desmoid in the abdominal wall and long-termed follow-up results. Methods:
      Clinical and follow-up data of 24 patients with giant desmoid in the abdominal
      wall underwent radical removal and immediate abdominal wall reconstruction in
      Diagnostic and Therapeutic Center of Hernia and Abdominal Wall Diseases, First
      Affiliated Hospital of People's Liberation Army General Hospital from October
      2006 to October 2016 were analyzed retrospectively. Twenty-one female patients
      with the mean age of 34.6 years and 3 male patients with the mean age of 42.6
      years were recruited. The minimal diameter of these tumors was 15 cm, and the
      maximal diameter was from xiphoid bone to pubic symphysis. Results: All of
      desmoids were removed radically and proved by the rapid pathologic examination.
      The size of abdominal wall defect after desmoids removal were 483 (21 cm*23 cm)
      to 2 100 cm(2) (35 cm*60 cm), averaged 945 cm(2) (27 cm*35 cm). All of defects
      were repaired with compound synthetic prosthesis using bridging procedure. Twenty
      one patients were recovered smoothly and got primary wound healing. Three
      patients had prosthesis infected during 1 month postoperatively and 1 patient
      recovered with conservative therapy, the other 2 patients underwent infected
      prosthesis removal at 2 weeks and 3 months postoperatively, respectively. Twenty
      two patients were followed up with the period of 12 to 121 months and the median
      period was 63 months. No marginal neoplasm recurrence, incisional hernia, and
      abdominal wall bulge happened. Eight patients developped fresh desmoids in the
      abdominal cavity or in the back. Two patients died because of intestinal
      obstruction due to desmoid infiltration, and the other 6 patients still survived
      along with stable desmoids. Conclusions: Radical removal for patients with giant
      desmoid in the abdominal wall is an ideal therapeutic method, and compound
      synthetic patch can be used to repair huge abdominal wall defect, even the defect
      compromised all of abdominal wall. The long-termed follow-up results showed these
      procedures had not put bad influence on the quality of patients' life.

PMID- 29325355
TI  - [Comparison of prognosis between invasive micropapillary carcinoma and invasive
      ductal carcinoma of breast: a single center, retrospective case-control study].
AB  - Objective: To elucidate the clinicopathological characters and prognostic factors
      of invasive micropapillary carcinoma of the breast (IMPC) by compared with
      invasive ductal carcinoma, not otherwise specified of the breast (IDC). Methods:
      The retrospective study was performed with female patients who had undergone
      curative resection for breast cancer without neoadjuvant chemotherapy from June
      2008 to April 2016 in Breast Center of Beijing Hospital. Forty-seven mixed or
      pure IMPC patients and 93 pure IDC patients(admitted in the same center from
      October 2008 to January 2016 ) were matched for tumor stage, nodal status and
      age. Follow-up was done every 3 to 6 months postoperatively. The deadline was
      July 31, 2016. The curves of disease free survival and overall survival were
      drawn by the Kaplan-Meier method, and survival rates were compared by means of
      the Log-rank test. Potential prognostic variables that were identified on
      univariate analysis were analyzed with Cox's proportional hazards regression
      model for multivariate analysis. The chi(2) test or Fisher's exact test was used
      to compare distributions across 2 groups and the Mann-Whitney U test or t test
      was used to analyze the medians or means of 2 groups. Results: With exact
      matches, the rates of lymphovascular invasion (LVI) (29.8% vs. 12.9%,
      chi(2)=5.885, P=0.015)and histological grade 3 (40.4% vs. 21.5%, chi(2)=-2.690,
      P=0.007) were both significantly higher in patients with IMPC than that in IDC
      group, but the survival between the two pathological types were not significantly
      different (all P>0.05). The percent of IMPC component didn't influence the
      clinicopathologic characters (all P >0.05), but a significantly longer median
      disease free survival (chi(2)=11.731, P=0.001) when the patients had more than
      50% of IMPC component was found. Conclusions: Higher rates of LVI and
      histological grade 3 were found in IMPC than that in IDC, but the survival was
      comparable between the two groups. A longer DFS occurred in patients with IMPC
      component more than 50%.

PMID- 29325356
TI  - [The role and significance of digital reconstruction technique in liver segments
      based on portal vein structure].
AB  - Objective: To study the segment of liver according to the large amount of three
      dimensional(3D) reconstructive images of normal human livers and the vascular
      system, and to recognize the basic functional liver unit based on the anatomic
      features of the intrahepatic portal veins. Methods: The enhanced CT primitive
      DICOM files of 1 260 normal human livers from different age groups who treated
      from October 2013 to February 2017 provided by 16 hospitals were analyzed using
      the computer-aided surgery system.The 3D liver and liver vascular system were
      reconstructed, and the digital liver 3D model was established.The vascular
      morphology, anatomical features, and anatomical distributions of intrahepatic
      portal veins were statistically analyzed. Results: The digital liver model
      obtained from the 3D reconstruction of CAS displayed clear intrahepatic portal
      vein vessels of level four.Perform a digital liver segments study based on the
      analysis of level four vascular distribution areas.As the less anatomical
      variation of left hepatic portal vein, the liver was classified into four types
      of liver segmentation mainly based on right hepatic portal vein.Type A was
      similar to Couinaud or Cho's segmentation, containing 8 segments(537 cases,
      42.62%). Type B contained 9 segments as there are three ramifications of right
      anterior portal vein(464 cases, 36.82%). The main difference for Type C was the
      variation of right-posterior portal vein which was sector shape(102 cases,
      8.10%). Type D contained the cases with special portal vein variations, which
      needs three-dimensional simulation to design individualized liver resection
      plan(157 cases, 12.46%). These results showed that there was no significant
      difference in liver segmental typing between genders(chi(2)=2.179, P=0.536) and
      did not reveal any significant difference in liver segmental typing among the
      different age groups(chi(2)=0.357, P=0.949). Conclusions: The 3D digital liver
      model can demonstrate the true 3D anatomical structures, and its spatial vascular
      variations.The observation of anatomic features, distribution areas of
      intrahepatic portal veins and individualized liver segmentation achieved via
      digital medical 3D visualization technology is of great value for understand the
      complexity of liver anatomy and to guide the precise hepatectomy.

PMID- 29325357
TI  - [Impact of primary tumor site on the prognosis in different stage colorectal
      cancer patients after radical resection].
AB  - Objective: To analyze the effect to the prognosis of tumor site on the patients
      of colorectal cancer after curative resection with different stage. Methods:
      Clinicopathological and follow-up data of 2 097 colorectal carcinoma cases
      undergoing resection at Fourth Hospital of Hebei Medical University from January
      2008 to March 2015 were retrospectively analyzed. There were 421 patients in left
      sided colorectal cancer (LCC) group (including carcinoma in cecum, ascending
      colon , hepatic flexure, and transvers colon) , 386 in right-sided colorectal
      cancer (RCC) group (including carcinoma in splenic flexure, descending colon and
      sigmoid colon) and 1 290 in rectal cancer (RECC) group. Clinicopathologic
      features in patients with different tumor location were compared. 5-year overall
      survival rate were compared among the 3 groups. Patients were stratified by
      different stage to analyze the effect of tumor location on the prognosis.
      chi(2)test and Kruskal-Wallis rank-sum test were used to compare the
      clinicopathological features among the 3 groups, Kaplan-Meier curve and Log-rank
      test were used to analyze prognosis, respectively. Results: No significant
      differences were identified between the three groups in age, family history, N
      stage and intestinal obstruction. Significant difference were found in gender
      among LCC, RCC and RECC group (male were 62.5% vs. 54.9% vs.56.3%, chi(2)=6.040,
      P=0.049) . Compared with LCC group and RCC group, RECC group had more well and
      moderately differentiated adenocarcinoma patients (89.7% vs. 86.0% vs. 82.4%,
      chi(2)=10.712 and 17.385, P=0.013 and 0.001) , more stage I patients (17.1% vs.
      6.9% vs. 6.5%, chi(2)=37.459 and 37.208, P=0.000 and 0.000) , and less likely to
      be stage T4 (44.7% vs. 76.7% vs.78.5%, chi(2)=128.015 and 133.704, P=0.000 and
      0.000), metastasis (2.6% vs. 5.7% vs. 3.6%, chi(2)=1 417.167 and 1 424.217,
      P=0.000 and 0.000) and intestinal obstruction (11.3% vs. 21.1% vs. 24.4%,
      chi(2)=25.846 and 41.141, P=0.000 and 0.000). Five-year survival rate reduced in
      turn in the patients with RECC, LCC and RCC(70.9%, 59.8%, 58.9%, chi(2)=11.577,
      P=0.009). In the subgroup of stage III, patients with different tumor location
      had different overall survival (chi(2)=9.878, P=0.007). Compared to right-sided
      colon cancer patients, rectal ones had significantly better overall survival
      (chi(2)=9.271, P=0.002); but in the subgroup of stage I, II and stage IV,
      patients with different tumor location had similar overall survival (P were
      0.124, 0.888, 0.263, respectively). Conclusions: Colorectal cancer patients with
      tumor location had different clinicopathologic features. Patients with rectal
      cancer had better five-year survival rate than those with left located and right
      located colon cancer. Tumor location had different effects on the prognosis
      according to the different TNM stage-subgroups.

PMID- 29325359
TI  - [New strategies for the diagnosis and treatemtn of hypertrophic cardiomyopathy].

PMID- 29325358
TI  - [Correlation between of aortic dissection onset and climate change].
AB  - Objective: To explore the relationship between the incidence of aortic dissection
      and climate change. Methods: The characteristics of 345 acute aortic dissection
      patients came from Beijing in Department of Vascular Surgery, Fu Wai Hospital,
      National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences,
      Peking Union Medical College from January 2005 to December 2015 were analyzed,
      retrospectively. There were 266 male and 79 female patients with a mean age of
      (49+/-12) years. There were 209 cases of Stanford type A aortic dissection, and
      136 cases of type B. According to Fuwai aortic dissection classification: type A
      8 cases, type B 95 cases, type Cp 13 cases, type Ct 187 cases, type Cd 40 cases,
      type D 2 cases. Meanwhile, monthly maximum temperature, minimum temperature,
      average temperature, average pressure, amount of rainfall, sunshine, relative
      humidity and other meteorological data were collected. Rank-sum test was used to
      analyze the difference of onset of aortic dissection in different seasons and
      months. Generalized additive models were implied to explore climate change and
      the onset of aortic dissection. Results: The onset of aortic dissection was
      related to season. Winter had higher morbidity compared to summer (M(Q(R)): 3(2)
      vs. 2(2), Z=1.97, P=0.05). The occurrence of aortic dissection was associated
      with month.December had the largest quantity, July had the least (2(3) vs. 2(1),
      Z=2.42, P=0.02). The mean temperature was statistically significant for
      indicating the change of aortic dissection onset. It meaned that onset
      probability was increased with the decrease of temperature (RR=1.01, 95%CI: 1.00
      to 1.02, P=0.04). Conclusions: The onset of aortic dissection had something to do
      with season and month. The incidence of aortic dissection increases with
      temperature decreases.

PMID- 29325360
TI  - [Update on Staphylococcus lugdunensis infective endocarditis].

PMID- 29325361
TI  - [Guidelines for the diagnosis and treatment for Chinese adult patients with
      hypertrophic cardiomyopathy].

PMID- 29325362
TI  - [Predicting value of 2014 European guidelines risk prediction model for sudden
      cardiac death (HCM Risk-SCD) in Chinese patients with hypertrophic
      cardiomyopathy].
AB  - Objective: To evaluate the predicting value of the 2014 European Society of
      Cardiology (ESC) guidelines risk prediction model for sudden cardiac death (HCM
      Risk-SCD) in Chinese patients with hypertrophic cardiomyopathy (HCM), and to
      explore the predictors of adverse cardiovascular events in Chinese HCM patients.
      Methods: The study population consisted of a consecutive 207 HCM patients
      admitted in our center from October 2014 to October 2016. All patients were
      followed up to March 2017. The 5-year SCD probability of each patient was
      estimated using HCM Risk-SCD model based on electrocardiogram, echocardiography
      and cardiac magnetic resonance (CMR) examination results. The primary, second,
      and composite endpoints were recorded. The primary endpoint included SCD and
      appropriate ICD therapy, identical to the HCM Risk-SCD endpoint. The second
      endpoint included acute myocardial infarction, hospitalization for heart failure,
      thrombus embolism and end-stage HCM. The composite endpoint was either the
      primary or the second endpoint. Patients were divided into the 3 categories
      according to 5-year SCD probability assessed by HCM Risk-SCD model: low risk
      group<4%,intermediate risk group >=4% to<6%, and high risk group>=6%. Results:
      (1) Prevalence of endpoints: All 207 HCM patients completed the follow-up (350
      (230, 547) days). During follow-up, 8 (3.86%) patients reached the primary
      endpoints (3 cases of SCD, 3 cases of survival after defibrillation, and 2 cases
      of appropriate ICD discharge); 21 (10.14%) patients reached the second endpoints
      (1 case of acute myocardial infarction, 16 cases of heart failure
      hospitalization, 2 cases of thromboembolism, and 2 cases of end-stage HCM). (2)
      Predicting value of HCM Risk-SCD model: Patients with primary endpoints had
      higher prevalence of syncope and intermediate-high risk of 5-year SCD, as
      compared to those without primary endpoints (both P<0.05). (3) Predicting value
      of HCM Risk-SCD model: The low risk group included 122 patients (59%), the
      intermediate risk group 42 (20%), and the high risk group 43 (21%). There was a
      clear trend towards to higher heart rate, higher values of PTF(V1) and plane QRS
      T angle, higher left ventricular mass index (LVMI), elevated maximal left
      ventricular outflow tract pressure gradient (LVOT-PGmax), enlarged left atrial
      dimension(LAD) and volume index (LAVI), reduced systolic mitral annular velocity
      (s'), and higher late gadolinium enhancement (LGE) volume and mass in patients
      with high risk of 5-year of SCD, as compared to those with low-intermediate risk
      (all P<0.05). Moreover, 5-year SCD probability was positively correlated with
      heart rate, plane QRS-T angle, LVMI, LAVI, LGE%, and negatively correlated with
      s'(r=0.161, P=0.019; r=0.669, P=0.001; r=0.206, P=0.004; r=0.284, P=0.000;
      r=0.351, P=0.000; r= -0.245, P=0.001; respectively). (4) LAD, LAVI, e' and s'
      were independent predictors for poor outcomes. HCM patients with LAD>=39 mm,
      LAVI>=49.6 ml/m(2), e'<=6.5 cm/s and s'<=6.6 cm/s were more likely to have
      adverse cardiovascular events (AUC 0.702, 95%CI 0.604-0.799, P=0.001; AUC 0.700,
      95%CI 0.567-0.833, P=0.001; AUC 0.716, 95%CI 0.616-0.817, P=0.000; AUC 0.764,
      95%CI 0.676-0.853, P=0.000,respectively). Conclusions: The HCM Risk-SCD model is
      of value in predicting SCD for Chinese HCM patients. The plane QRS-T angle and
      LGE% are the best predictors of 5-year SCD risk in Chinese HCM patients.
      Moreover, conventional echocardiographic parameters, including LAD, LAVI, e' and
      s', are useful to predict adverse cardiovascular events among Chinese HCM
      patients.

PMID- 29325363
TI  - [Related factors for the development of fulminant myocarditis in adults].
AB  - Objective: To determine the early recognizable factors related to patients with
      fulminant myocarditis. Methods: Medical records from 60 adult patients who were
      diagnosed with acute viral myocarditis from January 2003 to September 2016 in our
      hospital were retrospectively reviewed, and divided into the fulminant group
      (n=9) and the non-fulminant group (n=51). Clinical presentations, biochemical
      markers, electrocardiography and echocardiography features on admission were
      analyzed. Results: Prevalence of syncope (33.3%(3/9) vs. 2.0% (1/51), P=0.009)
      and fatigue (77.8% (7/9) vs. 21.6% (11/51) , P=0.002) was significantly higher,
      while the duration from flu-like syndromes to chest discomfort was shorter
      ((2.0+/-1.8) days vs. (4.5+/-3.5) days, P=0.041) in the fulminant group than that
      in the non-fulminant group. Systolic blood pressare (SBP) ((94+/-14) mmHg(1
      mmHg=0.133 kPa) vs. (117+/-12)mmHg, P=0.001) and left ventricular ejection
      fraction((49+/-12)% vs. (60+/-13)%, P=0.016) were significantly lower, while
      heart rate ((99+/-20)bpm vs. (84+/-19)bpm, P=0.040) and NT-proBNP concentration
      ((7 962 (1 470, 23 849) ng/L vs. 1 771 (45, 2 380) ng/L, P=0.000) were
      significantly higher in the fulminant group than those in the non-fulminant
      group. PR interval was longer (199 (140, 416) ms vs. 156 (112, 204) ms, P=0.021),
      QRS complex was wider ((127+/-14)ms vs. (95+/-13)ms, t=-6.647, P<0.001) in the
      fulminant group than those in the non-fulminant group. Prolonged QRS
      duration>=120 ms was more often in fulminant group (77.8%(7/9) vs. 5.9%(3/51),
      P=0.000). Multivariate analysis revealed that PR interval (adjusted odd ratio
      1.044, 95%CI 1.005-1.084, P=0.025) and QRS complex width (adjusted odd ratio
      1.252, 95%CI 1.045-1.501, P=0.015) were the independent risk factors
      significantly associated with fulminant myocarditis. Conclusions: The risk of a
      fulminant course of acute myocarditis is higher in patients with elevated NT
      proBNP, reduced left ventricular ejection fraction, and conduction disturbances
      at admission. Prolonged PR interval and widened QRS complex on admission are
      independent risk factors for developing fulminant myocarditis in adult patients
      with acute viral myocarditis.

PMID- 29325364
TI  - [The efficacy and safety of coil embolization of septal branch in the treatment
      of patients with obstructive hypertrophic cardiomyopathy].
AB  - Objective: To observe the clinical efficacy and safety of coil embolization of
      septal branch in the treatment of obstructive hypertrophic cardiomyopathy (HOCM).
      Methods: Eighteen patients with HOCM hospitalized in our department from
      September 2014 to October 2016 were enrolled in this study. There were 12 males
      and 6 females in this cohort and the age of patients ranged from 22 to 64 years
      old. Left ventricular outflow tract gradient (LVOTG) was derived from
      echocardiographic apical five-chamber view at pre-operation and at 48 hours and 6
      months post operation. 24-hour Holter ECG examination was performed to assess the
      ventricular tachycardia, atrial fibrillation, atrioventricular block at 3 days
      and 6 months after the interventional operation. Routine ECG and creatine kinase
      MB (CK-MB) examination were performed at pre-operation, at 6, 24 and 48 hours
      post operation. Cardiac troponin T (cTnT) was detected at pre-operation, at 24,
      48 hours and 6 days post operation. The clinical symptoms (including chest
      tightness, chest pain, shortness of breath, syncope) and NYHA classification were
      assessed at 1, 6 months after the operation by telephone follow-up or outpatient
      clinic visit. Results: The average preoperative LVOTG detected by cardiac
      catheter was 103.6 (92.0, 115.0) mmHg (1 mmHg=0.133 kPa) , and the average LVOTG
      significantly reduced to 44.3 (41.6, 47.2) mmHg immediately after operation
      (P<0.01). The average ventricular septal thickness at 48 hours (19.2+/-3.1) mm
      and 6 months (17.8+/-2.8) mm after operation tended to be lower than the
      preoperative ventricular septal thickness ((20.4+/-3.5) mm, P>0.05). The
      echocardiographic derived average LVOTG at 48 hours and 6 months after operation
      was 42.9 (41.1, 45.5) and 39.1 (37.5, 41.0) mmHg, which were significant lower
      than the preoperative average LVOTG (94.3 (88.5, 101.8) mmHg, both P<0.01). LVOTG
      at 6 months after operation was significantly lower than that at 48 hours after
      the operation (P<0.05). The NYHA classification at 6 months after operation was
      significantly improved compared to pre-operation NYHA classification (P<0.01).
      During and after the operation, there was no complete atrioventricular block and
      ventricular tachycardia, no patient developed anterior wall and inferior
      myocardial infarction. Only one patient experienced transient left bundle branch
      block. During the 6 months following-up, there was no death, syncope, chest pain,
      palpitations, shortness of breath, paroxysmal dyspnea and/or lower extremity
      edema, ventricular tachycardia, atrioventricular block and atrial fibrillation,
      complete atrioventricular block and ventricular arrhythmia. Conclusion: The coil
      embolization of septal branch is effective and safe for the treatment of patients
      with HOCM.

PMID- 29325365
TI  - [Efficacy comparison of 3 strategies for real-world stable coronary artery
      disease patients with three-vessel disease].
AB  - Objective: To compare the effectiveness of percutaneous coronary intervention
      (PCI), coronary artery bypass grafting (CABG) or medical therapy (MT) alone for
      real-world stable coronary artery disease (SCAD) patients with three-vessel
      disease (TVD) in mainland China. Methods: A total of 8 943 consecutive cases with
      TVD hospitalized in our center from April 2004 to February 2011 were screened for
      this study. In this cohort, 3 435 cases diagnosed as SCAD were analyzed. PCI,
      CABG, MT alone were performed in 1 313 (38.2%), 1 259 (36.7%) and 863 (25.1%)
      patients, respectively. Propensity score matching (PSM) analysis using nearest
      neighbor matching with a 1?1 ratio was applied, and 758 pairs of CABG and PCI
      groups, 552 pairs of PCI and MT groups, 639 pairs of CABG and MT groups were
      selected, respectively. 1- and 2-year clinical outcomes were evaluated among PCI,
      CABG and MT group. Kaplan-Meier curves and multivariable Cox regression method
      were used for survival analysis. Results: Significant differences were found at
      baseline between PCI, CABG and MT group, including age, gender, body mass index,
      family history of coronary artery disease, hyperlipidemia, diabetes mellitus,
      previous myocardial infarction, stroke, previous revascularization, peripheral
      vascular disease, SNYTAX score, left ventricular ejection fraction, hemoglobin,
      serum creatinine, high-sensitivity C-reactive protein, triglyceride and
      medication (all P<0.05) . All-cause death rates of 1- and 2-year follow-up of
      PCI, CABG and MT group were 0.6% (8/1 313), 1.1% (14/1 259), 3.4% (29/863)
      (P<0.001) and 1.1%(14/1 313), 1.5%(19/1 259), 7.3%(63/863) (P<0.001),
      respectively. Multivariate Cox regression analysis showed that 1-year MACCE rate
      (HR=0.51, 95%CI 0.33-0.77, P=0.001) was significantly reduced, due to the
      significant decrease of myocardial infarction (MI) rate (HR=0.09, 95%CI 0.01
      0.76, P=0.027) and repeat revascularization rate (HR=0.21, 95%CI 0.10-0.41,
      P<0.001) in CABG group compared to PCI group, while all-cause death (HR=1.21,
      95%CI 0.48-3.00, P=0.69) and stroke rate (HR=2.31, 95%CI 0.82-6.47, P=0.112) were
      similar between 2 groups. 2-year outcome showed CABG was associated with higher
      stroke rate (HR=2.20, 95%CI 1.06-4.55, P=0.034) and lower MI (HR=0.19, 95%CI 0.06
      0.59, P=0.004) and repeat revascularization rate (HR=0.22, 95%CI 0.13-0.37,
      P<0.001), and lower MACCE rate (HR=0.49, 95%CI 0.36-0.68, P<0.001). Compared to
      MT group, 2-year all-cause death (HR=0.22, 95%CI 0.12-0.42, P<0.001) and MACCE
      rate (HR=0.63, 95%CI 0.47-0.83, P=0.001) were lower in PCI group, while 2-year
      all-cause death (HR=0.21, 95%CI 0.13-0.37, P<0.001), MACCE (HR=0.31, 95%CI 0.23
      0.42, P<0.001), MI (HR=0.19, 95%CI 0.06-0.60, P=0.004) and repeat
      revascularization rate (HR=0.24, 95%CI 0.13-0.41, P<0.001) were lower in CABG
      group. Results of multivariate Cox regression analysis after PSM were consistent
      with above results. Conclusion: For SCAD patients with TVD, CABG shows better
      effectiveness by reducing MI and revascularization risk as compared to PCI, even
      though stroke risk is somehow higher in CABG patients. Patients received MT alone
      are associated with worse outcomes than those undergoing revascularization
      strategies.

PMID- 29325366
TI  - [Outcome of patients with coronary artery disease and left ventricular ejection
      fraction less than 50% undergoing percutaneous coronary intervention].
AB  - Objective: To investigate the in-hospital and long-term outcomes of patients with
      left ventricular ejection fraction (LVEF) <50% undergoing percutaneous coronary
      intervention (PCI) . Methods: From January to December 2013, 10 445 consecutive
      patients who underwent PCI in Fuwai Hospital and the LVEF value was available
      were prospectively included. The patients were divided into LVEF>=50% group (9
      896 cases) and LVEF<50% group (549 cases) . The in-hospital and 2-year clinical
      outcomes were compared between the 2 groups. The association between LVEF<50% and
      clinical outcomes was assessed using multivariable Cox regression analysis.
      Results: (1) Compared with LVEF >=50% group, LVEF< 50% group had higher rates of
      in-hospital all-cause death (1.1% (6/549) vs. 0.2% (17/9 896) , P<0.01) , cardiac
      death (1.1% (6/549) vs. 0.1% (12/9 896) , P<0.01) , in-stent thrombosis (0.7%
      (4/549) vs. 0.2% (18/9 896) , P<0.01) , myocardial infarction (2.4% (13/549) vs.
      1.2% (121/9 896) , P<0.05) ,and major adverse cardiovascular and cerebrovascular
      events (MACCE) which including death, myocardial infarction, revascularization,
      in-stent thrombosis, and stroke (3.6% (20/549) vs. 1.4% (137/9 896) , P<0.01) .
      (2) A total of 10 388 (99.5%) patients completed 2-year follow-up. Compared with
      LVEF >=50% group, LVEF<50% group had higher rates of 2-year all-cause death (4.7%
      (26/549) vs. 1.0% (101/9 896) , P<0.01) , cardiac death (4.0% (22/549) vs. 0.5%
      (50/9 896) , P<0.01) , in-stent thrombosis (3.1% (17/549) vs. 0.7% (71/9 896) ,
      P<0.001) , myocardial infarction (4.2% (23/549) vs. 1.9% (186/9 896) , P<0.01)
      ,and MACCE (17.9% (98/549) vs. 11.8% (1 172/9 896) , P<0.01) . There were no
      significant differences on the rates of 2-year target-vessel revascularization,
      bleeding and stroke between the two groups. (3) The multivariable Cox regression
      analysis demonstrated that LVEF< 50% was the independent risk factor of 2-year
      all-cause death (HR=2.47, 95%CI 1.49-4.08, P<0.01) , cardiac death (HR=3.25,
      95%CI 1.79-5.90, P<0.01) , in-stent thrombosis (HR=4.19, 95%CI 2.39-7.34, P<0.01)
      , myocardial infarction (HR=2.00, 95%CI 1.26-3.16, P<0.01) , and MACCE (HR=1.40,
      95%CI 1.13-1.74, P<0.01) . (4) After propensity score matching, all in-hospital
      outcomes were similar between the two groups, including all-cause death, cardiac
      death, in-stent thrombosis, myocardial infarction, revascularization, bleeding,
      stroke, and MACCE (all P>0.05) . After propensity score matching,the
      multivariable Cox regression analysis demonstrated that LVEF<50% was still an
      independent risk factor of 2-year all-cause death (HR=3.08, 95%CI 1.37-6.89,
      P<0.01) , cardiac death (HR= 4.12, 95%CI 1.53-11.07, P<0.01) ,and in-stent
      thrombosis (HR=3.82, 95%CI 1.27-11.5, P<0.05) . Conclusion: LVEF< 50% is an
      independent risk factor of 2-year all-cause death, cardiac death, and in-stent
      thrombosis in patients undergoing PCI, but it does not increase the risk of
      target-vessel revascularization, bleeding or stroke.

PMID- 29325367
TI  - [Effects of aerobic exercise combined with resistance training on the
      cardiorespiratory fitness and exercise capacity of patients with stable coronary
      artery disease].
AB  - Objective: To observe the effects of aerobic exercise combined with resistance
      training on the cardiorespiratory fitness and exercise capacity of patients with
      stable coronary artery disease (CAD) . Methods: From June 2014 to December 2015,
      73 patients with stable CAD in our department were recruited and randomly
      assigned to two groups: the control group (n=38) and the exercise group (n=35) .
      Patients in both groups received conventional medical treatment for CAD and
      related cardiac health education. While for patients in exercise group, a twelve
      week aerobic exercise combined with resistance training program were applied on
      top of conventional treatment and health education. Cardiorespiratory fitness and
      exercise capacity were evaluated by cardiopulmonary exercise testing. Results:
      (1) The exercise capacity was significantly increased in the exercise group after
      12 weeks training as compared to baseline level: peak oxygen uptake per kilogram
      ( (26.25+/-5.14) ml.kg(-1).min(-1) vs. (20.88+/-4.59) ml.kg(-1).min(-1)) ,
      anaerobic threshold ( (15.24+/-2.75) ml.kg(-1).min(-1) vs. (13.52+/-2.92) ml.kg(
      1).min(-1)], peak oxygen pulse ( (11.91+/-2.89) ml/beat vs. (9.77+/-2.49)
      ml/beat) , peak Watts ( (113.2+/-34.0) W vs. (103.7+/-27.9) W) , peak metabolic
      equivalent ( (7.57+/-1.46) METs vs. (6.00+/-1.32) METs) (all P<0.05 vs. baseline)
      . (2) The degree of improvement of peak oxygen uptake per kilogram ( (26.25+/
      5.14) ml.kg(-1).min(-1) vs. (22.32+/-4.00) ml.kg(-1).min(-1)) , anaerobic
      threshold ( (15.24+/-2.75) ml.kg(-1).min(-1) vs. (13.76+/-2.51) ml.kg(-1).min(
      1)) , peak oxygen pulse ( (11.91+/-2.89) ml/beat vs. (9.99+/-2.15) ml/beat) and
      peak metabolic equivalent ( (7.57+/-1.46) METs vs. (6.47+/-1.17) METs) were
      significantly higher in exercise group than in control group (all P<0.05) .
      Conclusion: Aerobic training at an aerobic threshold level combined with Thera
      band resistance training is safe for patients with stable coronary artery
      disease. This combined exercise program can significantly improve the
      cardiorespiratory fitness and exercise capacity of patients with stable coronary
      artery disease.

PMID- 29325368
TI  - [The effects and related mechanism of salvianolate on rats with myocardial
      ischemia-reperfusion injury].
AB  - Objective: To investigate the effect and related mechanism of salvianolate on
      myocardial ischemia-reperfusion (I/R) injury in rats. Methods: Thirty-six adult
      Sprague-Dawley rats were divided into three groups (n=12 each) using random
      number table method: control group (coronary artery was not ligated) , I/R group
      (myocardial I/R model was established by ligation and opening of left anterior
      descending coronary artery) , and salvianolate+I/R group (5 mg/kg of salvianolate
      was injected through the tail vein at the time of reperfusion)
      .Triphenyltetrazolium chloride (TTC) stain was utilized to measure the myocardial
      infarct size. The ELISA method was used to detect myocardial necrotic markers,
      including cardiac troponin T (TnT) , creatine kinase-MB (CK-MB) and lactate
      dehydrogenase (LDH) . Terminal deoxynucleotidyl transferase dUTP nick end
      labeling (TUNEL) staining was used to analyses the levels of apoptosis. The
      levels of cleaved Caspase-3 protein were analyzed with Western blot.Cold
      luminescence method was used to detect the ATP level of myocardial tissue. The
      levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in myocardial tissue were detected
      by immunofluorescence. Results: (1) The infarct size in control group, I/R group
      and salvianolate+I/R group were 0, (23.90+/-5.66) %, and (12.06+/-5.97) %,
      respectively (P<0.01 or 0.05) . (2) The TnT level was (0.04+/-0.03) , (16.96+/
      2.80) , and (6.95+/-2.31) ng/ml, the CK-MB level was (43.6+/-23.5) , (1 135.8+/
      180.6) ,and (390.3+/-121.5) U/L, the LDH level was (119.0+/-58.6) , (1 838.6+/
      543.8) , and (631.6+/-228.3) U/L in control group, I/R group and salvianolate+I/R
      group, all significantly lower in salvianolate+I/R group than in I/R group (all
      P<0.01) . (3) The rate of TUNEL positive myocardial cells were (1.07+/-1.16) %,
      (21.36+/-4.11) %,and (13.30+/-3.67) % in control group, I/R group,and
      salvianolate+I/R group (all P<0.01) . (4) The cleaved Caspase-3 expression was
      0.11+/-0.05, 0.84+/-0.20,and 0.43+/-0.09 in control group, I/R group, and
      salvianolate+I/R group (all P<0.01) . (5) The ATP level of myocardial tissue was
      (100.0+/-0.0) %, (34.2+/-9.2) %,and (62.1+/-18.0) % respectively in control
      group, I/R group, and salvianolate+I/R group (all P<0.01) . (6) There was almost
      no 8-OHdG expression in the myocardial tissue of control group. The expression of
      8-OHdG in the myocardial tissue of I/R group was greater than that of the control
      group. The expression of 8-OHdG in the myocardial tissue of salvianolate+I/R
      group was less than that of the I/R group. Conclusion: Salvianolate may alleviate
      myocardial I/R injury of rat through reducing the mitochondrial DNA oxidative
      damage, protecting mitochondrial function and inhibiting the apoptosis of
      myocardial cells.

PMID- 29325369
TI  - [CD137 signaling promotes the formation of plaque calcification via inhibiting
      the fusion of autophagy and lysosomal in Apo E(-/-) mice].
AB  - Objective: To investigate whether CD137 signaling promoted the formation of
      atherosclerotic plaque calcification by inhibiting the fusion of autophagosome
      and lysosome. Methods: (1) In vivo, CD137 agonist antibody and anti-CD137
      antibody were used to stimulate and inhibit the CD137 signaling, respectively.
      Fifteen Apo E(-/-) mice were randomly divided into three groups: control group
      (intraperitoneal injection of IgG2b 200 ug) , CD137 agonist group
      (intraperitoneal injection of CD137 agonist antibody 200 ug) , anti-CD137 group
      (pretreatment with 200 ug anti-CD137 antibody for 24 hours, then injection of
      CD137 agonist antibody) . (2) In vitro, primary culture of mouse aortic VSMCs
      obtained through adherence methods for tissues explants. The cells was divided
      into three groups: control group, agonist-CD137 group (CD137 agonist antibody 10
      MUg/ml) , and anti-CD137 group (pretreatment with 10 MUg/ml anti-CD137 antibody
      for 60 minutes, then incubated with 10 MUg/ml CD137 agonist antibody) . Von kossa
      staining was used to detect the calcification in the cell and plaque.
      Immunohistochemical staining was used to observe the expression of LC3B, Beclin 1
      and p62 which are associated with autophagy. The levels of autophagy related
      protein (LC3) , Beclin 1, p62, and the expression of Runx2 and bone morphogenetic
      protein 2, which is associated with osteogenic differentiation in the VSMCs, were
      determined by Western blot. The autophagy flow of each group was detected by
      fluorescence microscopy. The autophagy was observed by transmission electron
      microscope in vivo and in vitro. Results: (1) In vivo, the calcified plaque area
      in CD137 agonist group was significantly larger than that in the control group
      (3.01%+/-0.45% vs. 0.27%+/-0.06%, P<0.01) , and calcified plaque area in anti
      CD137 group was significantly smaller compared with that in the CD137 agonist
      group (1.23%+/-0.39% vs. 3.01%+/-0.45%, P<0.05) . Immunohistochemical staining
      showed that the expression of early autophagy marker protein LC3B and Beclin 1
      were significantly upregulated in CD137 agonist group and anti-CD137 group than
      in control group, and the highest expression was observed in CD137 agonist group
      (P<0.05) . The expression of advanced autophagy marker protein p62 was higher in
      the CD137 agonist group than in the anti-CD137 group (P<0.05) . (2) In vitro, the
      ratio of autophagy related protein LC3 II/I and p62 protein expression were
      significantly higher in CD137 agonist group and anti-CD137 group than in control
      group (P<0.01) , while the expression of p62 protein was significantly higher in
      CD137 agonist group than that in anti-CD137 group (P<0.05) . In the cell
      calcification inducing experiment, the expression of BMP-2 and Runx2 protein was
      significantly higher in CD137 agonist group than that in control group (P<0.01) ,
      but the levels of BMP-2 and Runx2 protein were lower in anti-CD137 group than in
      CD137 agonist group (P<0.05) . Conclusion: Our results indicate that activation
      of CD137 signaling can promote the formation of atherosclerotic plaque
      calcification by inhibiting the fusion of autophagosome and lysosome.

PMID- 29325371
TI  - [A case of acute myocardial infarction manifested with headache as the only
      symptom].

PMID- 29325372
TI  - [Association between hypertension and emotional disorders: effect of
      psychological intervention].

PMID- 29325370
TI  - [Association between carotid artery plaques and all-cause mortality and
      cardiovascular events].
AB  - Objective: To observe the association of carotid artery plaque with all-cause
      mortality and cardiovascular events. Methods: A total of 7 017 participants who
      completed the carotid sonography examination between 2010 and 2011 were selected
      from the stroke and the elderly prospective cohort Kailuan study. The
      participants of stroke cohort received health examination between 2006 and 2007,
      and participants of elderly cohort received health examination between 2010 and
      2011. All participants were divided into plaque group (3 285 cases) and without
      plaque group (3 732 cases) according to with or without carotid artery plaque.The
      all-cause mortality and cardiovascular events were compared between the 2 groups.
      Multivariate Cox regression analysis was used to identify the association of
      carotid artery plaque with all-cause mortality and cardiovascular events.
      Results: (1) There were 4 297 male (61.2%) and 2 720 female (38.8%) in this
      cohort and participants were (58.1+/-11.8) years old. Age, systolic blood
      pressure, diastolic blood pressure, fasting plasma glucose, total cholesterol,
      low-density lipoprotein cholesterol, rates of male, smoking, drinking, history of
      hypertension and diabetes mellitus were higher in the plaque group than in the
      without plaque group, and high density lipoprotein cholesterol was lower in the
      plaque group than in the without plaque group (all P<0.01) at baseline. (2)
      During a follow-up period of (4.92+/-0.59) years, the incidence rates of all
      cause mortality in the plaque group and without plaque group were 5.5% (180/3
      285) and 1.5% (57/3 732) ,respectively (P<0.01) .The incidence rates of
      cardiovascular events in the plaque group and without plaque group were 3.8%
      (124/3 285) and 1.4% (52/3 732) , respectively (P<0.01) . (3) Multivariate Cox
      regression analysis showed that carotid plaque was an independent risk factor of
      all-cause mortality (HR=1.667, 95%CI 1.160-2.395, P<0.01) and cardiovascular
      events (HR=1.942, 95%CI 1.312-2.876, P<0.01) after adjusting for age, sex,
      systolic blood pressure, diastolic blood pressure, fasting plasma glucose, body
      mass index, total cholesterol,low density lipoprotein cholesterol, high density
      lipoprotein cholesterol, smoking, drinking, history of hypertension and diabetes
      mellitus, and use of lipid-regulating drugs. Conclusion: Carotid plaque is an
      independent risk factor of all-cause mortality and cardiovascular events.
      Clinical Trial Registration Chinese Clinical Trials Registry, ChiCTR-TNC
      11001489.

PMID- 29325373
TI  - [The practice of inter-professional team approach for patients with chronic heart
      failure].

PMID- 29325374
TI  - [Research progress of treatment of myocardial infarction using angiogenesis
      factor].

PMID- 29325375
TI  - [Research progress on the association between Pin1 and cardiovascular diseases].

PMID- 29325376
TI  - [Research progress on the role of microRNAs in pulmonary hypertension].

PMID- 29325378
TI  - [Research progress on the role of regulators of G-protein signaling in the
      pathogenesis of myocardial hypertrophy].

PMID- 29325377
TI  - [Research progress on the role of exosomes in myocardial ischemia/reperfusion
      injury].

PMID- 29325379
TI  - [Pay attention to the clinical classification and individualized treatment of
      superior oblique palsy].
AB  - Superior oblique palsy (SOP) has many anatomic variations, and the accompanied
      paralysis generalization could stimulate the secondary changes of other extra
      ocular muscles. Therefore, the clinical manifestations of SOP can be various, and
      the surgical design is complicated and changeable. It is necessary to understand
      the clinical development, stages and types of SOP correctly, and to take into
      account the developmental characteristics of the superior oblique muscle and
      select the individualized treatment plan. In this article, the SOP
      manifestations, imaging features, clinical examination and personalized treatment
      options are discussed, in order to provide some reasonable treatment options for
      SOP surgery. (Chin J Ophthalmol, 2017, 53: 881-884).

PMID- 29325380
TI  - [Could binocular treatment be a substitute for patching].
AB  - Amblyopia is a common eye disease with a high prevalence in clinical practice of
      pediatric ophthalmology and strabismus. The primary treatment strategy for
      amblyopia is precise correction of refractive errors and patching of the dominant
      eye. The application of patching has a history of more than 200 years, and now is
      still the most effective method for treatment of amblyopia. Similar to the
      principle of traditional patching, atropine penalization has been testified that
      it can be used as an initial treatment for amblyopia with similar therapeutic
      effects as patching. In the past decade, binocular treatment has been proposed as
      a strategy for the treatment of amblyopia. Successively, different kinds of
      binocular treatment methods were reported by the researchers. This article
      systematically reviews all these methods reported in the recent years and their
      therapeutic effects. Most results about the therapeutic effect of binocular
      treatment are from the designers of the studies themselves, but in recent 2 years
      the results from monocenter or multicenter randomized controlled clinical trials
      to compare the therapeutic effects of binocular treatment and patching were
      reported. We hope to help colleagues have a comprehensive and objective
      understanding of the research progress on binocular treatment for amblyopia and
      thus keep a cool head on the question of whether binocular treatment could be a
      substitute for patching. (Chin J Ophthalmol, 2017, 53: 885-889).

PMID- 29325381
TI  - [Longterm surgery outcome of Mobius syndrome].
AB  - Objective: To investigate clinical features and the long-term surgery results of
      Mobius syndrome patients. Methods: This investigation presents a retrospective
      study of Mobius syndrome in 7 children we found since 2009. All 7 patients had
      MRI scan, ocular alignment in primary position, the limitation of versions and
      ductions and forced duction under general anesthesia. Early surgery is done to
      the 7 esotropia children. The pre-operative and post-operative outcomes,
      including the ocular alignment, deviation measurements and ocular rotations, were
      evaluated and compared. Results: MRI showed absence of uni- or bilateral CN6 and
      CN7 in all 7 patients. All 7 patients underwent extra large recession of medial
      rectus at the first surgery, (6.17+/-1.47) mm/eye. Variation of ocular deviation
      in the primary position within 6 months postoperatively in all patients,
      demonstrating that strabismus surgical stabilization needs time. Three patients
      with esotropia deviation>=40 degrees  preoperative were under corrected and
      needed the secondary operations. The average deviation in the primary position
      was +35.00 degrees +/-16.58 degrees  before surgery and +2.14 degrees +/-5.67
      degrees  after surgery(t=6.040, P<0.01). The abduction in affected eye is limited
      both pre and postoperatively and a smaller limitation of adduction after surgery.
      Conclusions: Mobius syndrome has been classified to congenital cranial
      dysinnervation disorders (CCDDs). We recommend MR recession as the first surgical
      choice because of the lack of abduction ability. Longterm surgical results were
      considered satisfactory, improving patient self-esteem and the parent
      satisfaction. (Chin J Ophthalmol, 2017, 53: 897-902).

PMID- 29325382
TI  - [Knapp procedure and modified Knapp procedure with Foster suture for the
      treatment of double elevator palsy].
AB  - Objective: To investigate the efficacy of Knapp procedure and modified Knapp
      procedure with Foster suture in the treatment of double elevator palsy(DEP).
      Methods: Retrospective study. Twenty-two patients with congenital DEP were
      underwent Knapp procedure (n=15) and modified Knapp procedure(n=7). The clinical
      data were retrospectively analyzed, including the preoperative and postoperative
      vertical deviation in the primary position, ocular motility, and binocular
      vision. Results: The average vertical deviation in the primary position was
      (34.7+/-8.6) prism diopters(PD) before surgery and (6.5+/-6.5) PD after surgery
      (t=30.41, P=0.00) in the group underwent Knapp procedure. The mean preoperative
      and postoperative deviations of the group underwent modified procedure were
      respectively (38.6+/-14.6) PD and (5.7+/-9.3)PD (t=15.33, P=0.00). The mean
      corrected vertical deviation of the latter (32.8+/-5.7) PD was greater than that
      of the former (28.1+/-3.6) PD(t=-2.39, P=0.03). The mean improved upgaze in the
      modified group (2.6+/-0.5) was more obvious than that in the Knapp group (1.9+/
      0.6) (t=2.41, P=0.02). There is no significant difference in the surgical effect
      on downgaze between two groups (U=43.00, P=0.54). Seven patients having binocular
      vision with abnormal head posture (AHP) before surgery obtained binocular single
      vision in the primary position and reading position after operations. AHP
      disappeared or reduced to less than 5 degrees . The surgical outcomes were
      satisfied in 72.7% patients. But the patients with >=40 PD preoperative vertical
      deviation were under-corrected and needed the further operations. Conclusions:
      Knapp procedure and modified Knapp procedure with Foster suture were the
      efficient procedures for treatment of DEP without restriction of ipsilateral
      inferior rectus. Both procedures can obviously correct the vertical deviation and
      improve upgaze without remarkable limitation of downgaze, which is good to obtain
      the binocular single vision in the primary and reading position. The modified
      procedure has more powerful effect on the corrected vertical deviation and
      improved upgaze. (Chin J Ophthalmol, 2017, 53: 903-907).

PMID- 29325383
TI  - [Clinical features and surgical outcomes of acute acquired comitant esotropia].
AB  - Objective: To investigate the clinical features and surgical outcomes of patients
      with acute acquired concomitant esotropia (AACE) type II(AACE-II) and type III
      (AACE-III). Methods: Retrospective case series analysis. Medical records of
      consecutive patients who underwent strabismus surgery for AACE-II and AACE-III in
      Shandong Provincial Hospital affiliated to Shandong University between January
      2011 and June 2016 with a minimum follow-up time of 3 months were collected. Each
      patient underwent a complete ophthalmological and orthoptic examination to
      exclude esotropia resulting from other reasons, and a systemic assessment to
      exclude AACE related to intracranial and systemic diseases. Surgical procedures
      were determined according to the esodeviations measured at distance and near and
      the different dominant eye of patients. A successful surgical alignment was
      defined as the distant and near deviation in the primary gaze within 8 prism
      diopters (PD) of orthophoria and no diplopia. Results: Twenty-nine patients were
      enrolled in this study, including 17 males and 12 females. The mean age of the
      patients was 22.14+/-15.13 years (range, 5-63 years). The median corrected visual
      acuity (LogMAR) of patients with AACE-IIwas 0 (range, 0.22 to 0), and that of
      patients with AACE-III was 0 (range, 0.10 to 0). The median esodeviation of
      patients with AACE-II at distance was 35 PD (range, 10 to 55 PD), and that at
      near was 35 PD (range, 20 to 60 PD). The median esodeviation of patients with
      AACE-III at distance was 30 PD (range, 12 to 50 PD), and that at near was 30 PD
      (range, 6 to 50 PD). When tested with the red filter test preoperatively, all the
      patients had an uncrossed horizontal diplopia with the same distance in left and
      right lateral fixations. With a mean follow-up time of 12.0+/-12.6 months, of all
      the 29 patients, 24 patients (83%) achieved successful surgical alignment after
      one surgery, and 5 patients (17%) were undercorrected or had recurrence, in whom
      4 were successfully aligned after repeated surgery (performed at a mean of 3.5
      months after the first surgery) and 1 was treated with the Fresnel press-on
      prism. At the last follow-up, of all the 28 patients successfully aligned, 20
      (71%) regained bifoveal fusion, 8 (29%) regained peripheral fusion, 17 (61%)
      regained normal stereopsis (stereoacuity <=60"), and 11 regained a certain degree
      of stereopsis (stereoacuity 80"-400"). The constituent ratio of biocular central
      fusion and peripheral fusion in patients with AACE-II had no significant
      difference from patients with AACE-III (chi(2)=0.235, P>0.05), and the
      constituent ratio of central stereopsis, macular stereopsis, and peripheral
      stereopsis in patients with AACE-II had no significant difference from patients
      with AACE-III (chi(2)=0.762, P>0.05). Conclusions: All patients exhibited the
      typical features of AACE, which included an acute onset of diplopia and comitant
      esotropia, a wide range of onset age of the patients, normal corrected visual
      acuity and ocular movements, a mean moderate level of esodeviation with a wide
      range, and a good binocular potential. According to the esodeviations measured at
      distance and near and the different dominant eye of patients, good oculomotor
      alignment and perceptual outcomes may be obtained in patients with AACE-IIand
      AACE-III. (Chin J Ophthalmol, 2017, 53: 908-916).

PMID- 29325384
TI  - [Diagnosis and treatment of strabismus caused by nasal endoscopic surgery].
AB  - Objective: Strabismus with diplopia is the main orbital complication of
      functional endoscopic sinus surgery (FESS). This study was to analyze clinical
      findings, treatment and outcomes of such cases. Methods: Retrospective case
      series. Twenty-three cases were divided into 3 groups based on the disease
      severity: group A, partial transection of the medial rectus muscle, group B,
      complete transection of the medical rectus, group C, transection of the medial
      rectus combined with the other orbital injuries. Complete ophthalmology
      examinations, including eye alignment, eye motility, force duction test, force
      generation test, general eye exam, and medical imaging (orbital CT or MRI), were
      performed for each case. The treatment included botulinum toxin (Botox) injection
      to the lateral rectus muscle, transposition of the vertical rectus muscle, and
      orbital surgery if needed. Results: In group A with Botox injection, all the
      cases achieved single vision in primary position, but still remained some
      adduction weakness. In group B treated by vertical transposition surgery combined
      with Botox, 22% of the cases got single vision in primary gaze. In group C, even
      with more efforts of treatment, the cases with orbital injury can only get
      cosmetic improvement, and diplopia and adduction dysfunction were found in most
      cases. Conclusions: Due to the variety of the complications of FESS, force
      duction test is a crucial exam to detect the direction and severity of synechia
      in the orbit, which will give solid information to surgery approach as well as
      prognosis. Botox injection at early stage will minimize the contraction of
      antagonist lateral rectus, helping to postpone the transposition surgery which
      may cause anterior segment ischemia when performed right after the medial rectus
      transection injury. Botox may even reduce the synechia by minimizing the scarring
      process. Partial vertical rectus transposition combined with muscle resection may
      effectively correct the eye misalignment in primary gaze and improve eye
      motility. The prognosis of FESS induced orbital complications is quite related
      with the severity of the injury. Botox combined with surgery may help medial
      rectus transection cases to achieve single vision in primary gaze, but when there
      is any other orbital injury, treatment may only improve cosmetic appearance.
      (Chin J Ophthalmol, 2017, 53: 917-923).

PMID- 29325385
TI  - [The effect of surgical methods and postoperative eye position on the quality of
      life in patients with intermittent exotropia].
AB  - Objective: To evaluate the effects of different surgical methods and
      postoperative eye positions on the quality of life of children with intermittent
      exotropia (IXT) and their parents 3 months following strabismus surgery. Methods:
      Clinical observation. One-hundred and eighty children aged 2 to 17 years with IXT
      who received surgical treatment were recruited. One parent of each child was
      investigated by using 2 kinds of the Chinese version of the Intermittent
      Exotropia Questionnaires (CIXTQ) within 1 weeks before and at 3 months after
      surgery: the parent proxy scale (for parents to assess children's health related
      quality of life (HRQoL)) and the parent scale (containing functional,
      psychosocial and surgery subscales; for parents to assess their HRQoL). One
      hundred and eighty children were divided into different groups according to the
      surgical. Methods Monocular surgery group, binocular surgery group and eye
      position after 3 months: undercorrection group, successful group, overcorrection
      group, to explore: (1) the change of scores before and after surgery. (2) the
      difference of score changes after surgery between monocular and binocular surgery
      groups. (3) the difference of score changes after surgery between different
      postoperative eye position groups. Results: Significant improvement in median
      scores was seen from pre-operation to 3months post-operatively for all the proxy
      scale (t=-9.585, P<0.001), the functional (t=-11.361, P<0.001), psychosocial (t=
      10.856, P<0.001) and surgery subscale (t=-11.622, P< 0.001) of parent scale. The
      change values from pre-operation to 3months post-operatively were not
      significantly different between monocular and binocular surgery groups for all
      the proxy scale (t=0.242, P=0.330), the functional (t=0.462, P=0.050),
      psychosocial (t=0.781, P=0.582) and surgery subscale (t=0.009, P=0.355) of parent
      scale, but significantly different between undercorrection, successful and
      overcorrection groups for the proxy scale (F=21.527, P<0.001), the functional
      (F=54.236, P<0.001), psychosocial (F=41.784, P<0.001) and surgery subscale
      (F=31.943, P<0.001). The scores of proxy scale and 3 parent subscales were all
      significantly improved (t=-13.639 to -6.059, P<0.05) after operation in both the
      undercorrection and successful groups, while significantly decreased in the
      overcorrection group (t=1.350-4.391, P<0.05). Conclusions: HRQoL can be improved
      significantly in both the undercorrection and successful groups, while decreased
      in the overcorrection group. (Chin J Ophthalmol, 2017, 53: 924-930).

PMID- 29325386
TI  - [The protective effect of the activation of NMDAR1/ERK1/2 signal pathway induced
      by levodopa on visual cortical neurons in monocular deprivation rats].
AB  - Objective: To investigate the protection effects of the activation of NMDAR1(NMDA
      receptor 1)/ERK1/2 signal pathway on visual cortex nerve cells induced by
      levodopa in amblyopia rats. Methods: SD rats of SPF grade, were randomly divided
      into for groups of 9, group A. Control, B. MD group, C. L-levodopa(20 mg.kg(
      1))+MD group, D. H-levodopa (80 mg.kg(-1))+MD group, E. H-levodopa+MD+MK801
      group, F. H-levodopa+MD+PD98059 group, G. MD+MK801 group, H. MD+PD98059 group, I.
      MD+DMSO group. Amblyopia rats were made by suture of the right eye. Levodopa was
      used to treatment amblyopia by gavage, and intervened by intracerebroventricular
      injection of MK801 and PD98059 respectively. The expression of NR1, p-ERK1/2,
      ERK1/2, NGF and c-FOS were detected by Western blotting. Nissl staining was used
      to detect morphological changes of neurons. Neuronal apoptosis was detected by
      TUNEL method, and detected the expression of Caspase-3, NGF and c-FOS by
      immunohistochemical staining. One/Two way Chi-square analysis was used for data
      analysis. LSD-t test was used as comparison between every two groups. Results:
      The morphology of Nissl bodies in neurons was complete and clear in A group, and
      the size of Nissl bodies got smaller, and caused karyopyknosis and loss of
      neurons in visual cortex of B group. Compared with A group, the apoptosis of
      visual cortical neurons(23.09+/-2.00 vs. 2.20+/-0.35, t=12.120, P=0.000) and the
      number of Caspase-3 postive cells (22.70+/-1.50 vs. 3.30+/-0.54, t=12.120,
      P=0.000)were significantly increased, the expression of NGF(0.31+/-0.04 vs.
      0.74+/-0.09, t=7.674, P=0.000) and c-FOS(0.25+/-0.03 vs. 0.57+/-0.07, t=5.919,
      P=0.000) and the rats of NGF(8.30+/-0.82 vs. 35.18+/-2.01, t=12.37, P=0.0000) and
      c-FOS (10.84+/-1.02 vs. 35.68+/-2.55, t=9.056, P=0.0001) postive cell were
      decreased significantly in B group. After treatment with levodopa, the morphology
      of neurons recovered, the apoptosis of visual cortical neurons relieved, the
      expression of NR1(0.75+/-0.09 vs. 0.40+/-0.05, t=8.528, P=0.001) and p
      ERK1/2(2.13+/-0.26 vs. 0.68+/-0.17, t=3.488, P=0.008) were increased
      significantly, and the rats of NGF (18.07+/-0.87 vs. 8.30+/-0.82, t=8.18,
      P=0.0000) and c-FOS (19.78+/-0.91 vs. 10.84+/-1.02, t=6.543, P=0.0001) postive
      cells were significantly increased. MK-801 or PD98059 intervention could
      effectively attenuate the effect of levodopa. It could effectively down-regulated
      the expression of NR1 (0.53+/-0.06 vs. 0.95+/-0.12, t=5.647, P=0.005) and p
      ERK1/2(1.52+/-0.18 vs. 2.58+/-0.30, t=3.091, P=0.013) interference with MK801 or
      PD98059 in MD rats. MK-801 or PD98059 intervention further promote the Nissl body
      volume reduced, neurons karyopyknosis, the apoptosis of visual cortical neurons
      and Caspase-3 expression, and restrain the expression of NGF and c-FOS.
      Conclusion: Levodopa played a protective role in visual cortex nerve cells of
      amblyopia rats at least partially through activation of NMDA-ERK1/2 signal
      pathway. (Chin J Ophthalmol, 2017, 53: 931-940).

PMID- 29325387
TI  - [Clinical effects of pediatric penetrating keratoplasty for congenital corneal
      opacity].
AB  - Objective: To report the clinical results of pediatric penetrating keratoplasty
      (PKP) in patients under 3 years old with congenital corneal opacity. Methods:
      Retrospective study. Sixteen eyes of 12 patients who were treated with PKP in
      Aier Eye Hospital Group from June 2009 to December 2016 were enrolled in this
      study. All the patients were diagnosed as congenital corneal opacities: 8 cases
      (11 eyes) with Peter's anomaly I, 2 cases (3 eyes) with sclerocornea, and 2 cases
      (2 eyes) with corneal dermoid tumor combined with iris synechia. Seven cases (7
      eyes) were under 1 year old. Eight cases (10 eyes) could not follow the light.
      Only 1 case (2 eyes) received PKP with extracapsular cataract extraction, and the
      others only had PKP. Postoperative examinations were performed more frequently
      than in adults, and sometimes general anesthesia was needed. Results: The follow
      up period was from 8 months to 6 years (33.17+/-22.60 months). The postoperative
      visual acuity improvement was found in all eyes from 1 week to 1 month after
      surgery except a 3-year-old patient with corneal dermoid tumor with serious
      esotropia. All the surgeries were successful without intraoperative
      complications. Graft rejection occurred in 4 cases (4 eyes). The graft of a 33
      month-old patient became semitransparent. The grafts of 2 cases under 1 year old
      were clear after drug therapy. And the vision of a 3-year-old patient with Peter
      anomaly improved obviously, but immune rejection occurred 2 years after surgery.
      The second PKP was performed, but rejection occurred again. Secondary glaucoma
      was found in the other eye early after operation; anti-glaucoma surgery failed,
      and the graft became cloudy. Graft infection associated with loosened sutures was
      observed in one case (2 eyes) of sclerocornea, and the second PKP failed.
      Conclusions: For the patients with congenital corneal opacities, there is often a
      noticeable visual improvement after PKP. Good postoperative care, appropriate
      amblyopia treatment and timely examination are the keys to success. (Chin J
      Ophthalmol, 2017, 53: 941-946).

PMID- 29325388
TI  - [The research advances of microRNA-184 and related ocular diseases].
AB  - microRNA-184 (miR-184) is a small, non-coding, endogenic RNA molecule of 22
      nucleotides in length. It is a highly conserved sequence throughout many
      different species. Multiple studies have demonstrated that miR-184 is an
      important factor in regulating gene expression at the post-transcriptional level.
      miR-184 plays vital roles in many biological processes, including development and
      differentiation in many tissues and organs. Meanwhile, the research on the
      physiological and pathological role of miR-184 in eyes draws more and more
      attention lately. Recent research indicates that miR-184 is highly expressed in
      the cornea and lens of mice. miR-184 plays crucial regulatory roles in several
      ocular diseases, such as neovascularization, keratoconus, endothelial dystrophy
      iris hypoplasia-congenital cataract-stromal thinning syndrome, corneal squamous
      cell carcinoma, age-related macular degeneration and cataract. Here we summarize
      and discuss the recent findings of miR-184 in its gene structure, gene expression
      and regulation, biological function and its relevance with ocular diseases. (Chin
      J Ophthalmol, 2017, 53: 950-955).

PMID- 29325389
TI  - [Development of en face optical coherence tomography and its application in
      ocular fundus diseases].
AB  - Optical coherence tomography (OCT) is able to obtain the cross-sectional image of
      the fundus noninvasively and quickly. The cross-sectional image in vivo almost
      matches the histological section of the retina. OCT has become the most important
      imaging tool in ophthalmology. Based on the latest OCT technology, en face OCT is
      a new imaging technique that reveals the structure of retinal and choroidal
      sections approximately paralleled to the retina surface. Compared to the
      conventional OCT, en face OCT provides more comprehensive information and makes
      more accurate diagnosis and assessment of the prognosis. En face OCT is widely
      used in ocular fundus diseases, such as macular epiretinal membrane, macular
      hole, macular edema, age-related macular degeneration and retinal vascular
      disease, glaucoma and neuro-ophthalmology. This article reviews the related
      concepts, principles and clinical applications of en face OCT. (Chin J
      Ophthalmol, 2017, 53: 956-960).

PMID- 29325390
TI  - Translation, Adaptation and Cross Language Validation of Tinnitus Handicap
      Inventory in Urdu.
AB  - BACKGROUND AND OBJECTIVES: Tinnitus is characterized as a perception of numerous
      auditory sounds in absence of external stimulus. Tinnitus can have a considerable
      consequence on a person's quality of life, and is considered to be very
      complicated to quantify. The aim of this study was to investigate the reliability
      and validity of Urdu translation of the Tinnitus Handicap Inventory (THI) in
      Pakistan. It was designed to assess the presence of various auditory sounds
      without the external stimulus. Scale consisted of 25 items having three subscales
      functional, emotional, and catastrophic. SUBJECTS AND METHODS: The study
      comprised into two stages, preliminary and main studies. The results of
      preliminary study revealed that the overall scale had high internal consistency
      [alpha coefficient of Urdu version of THI (THI-U)= 0.99, alpha coefficient of
      English version of THI=0.98]. The overall scale had test-retest correlation over
      a fifteen days period of interval (0.99). Main study was performed on 110
      tinnitus patients. The results of main study showed that the internal consistency
      and reliability of Urdu version was (alpha=0.93). The THI-U and its subscales
      demonstrated good internal consistency reliability ( alpha =0.81 to 0.86).
      RESULTS: High to moderate correlations were noted between tinnitus symptom
      ratings. A confirmatory factor analysis was used to validate the three subscales
      of THI-U, and high inter-correlations were found between the subscales also
      results revealed that a three-factor model for the THI-U was most tenable. The
      results displayed that the confirmatory factor analysis confirmed to validate the
      three subscales of THI-U. CONCLUSION: THI-U might present important information
      about precise facets of tinnitus distress along with diagnostic interviews in
      clinical practice.

PMID- 29325391
TI  - Frequency-Limiting Effects on Speech and Environmental Sound Identification for
      Cochlear Implant and Normal Hearing Listeners.
AB  - BACKGROUND AND OBJECTIVES: It is important to understand the frequency region of
      cues used, and not used, by cochlear implant (CI) recipients. Speech and
      environmental sound recognition by individuals with CI and normal-hearing (NH)
      was measured. Gradients were also computed to evaluate the pattern of change in
      identification performance with respect to the low-pass filtering or high-pass
      filtering cutoff frequencies. SUBJECTS AND METHODS: Frequency-limiting effects
      were implemented in the acoustic waveforms by passing the signals through low
      pass filters (LPFs) or high-pass filters (HPFs) with seven different cutoff
      frequencies. Identification of Korean vowels and consonants produced by a male
      and female speaker and environmental sounds was measured. Crossover frequencies
      were determined for each identification test, where the LPF and HPF conditions
      show the identical identification scores. RESULTS: CI and NH subjects showed
      changes in identification performance in a similar manner as a function of cutoff
      frequency for the LPF and HPF conditions, suggesting that the degraded spectral
      information in the acoustic signals may similarly constraint the identification
      performance for both subject groups. However, CI subjects were generally less
      efficient than NH subjects in using the limited spectral information for speech
      and environmental sound identification due to the inefficient coding of acoustic
      cues through the CI sound processors. CONCLUSIONS: This finding will provide
      vital information in Korean for understanding how different the frequency
      information is in receiving speech and environmental sounds by CI processor from
      normal hearing.

PMID- 29325392
TI  - Horizontal Localization in Simulated Unilateral Hearing Loss.
AB  - BACKGROUND AND OBJECTIVES: The ability to localize a sound source is one of the
      binaural hearing benefits in a horizontal plane based on interaural time
      difference and interaural intensity difference. Unilateral or bilateral
      asymmetric hearing loss will affect binaural hearing and lead to sound locating
      errors. In this cross sectional analytical descriptive study, the localization
      error was investigated when participants turned their heads to the sound source
      with closed eyes and after simulating unilateral hearing loss by placing earplugs
      inside the right ear canal. SUBJECTS AND METHODS: This cross sectional analytical
      descriptive study was carried out on 30 right-handed adults, 22 female and 8 male
      (average: 25 years, standard deviation: 3.16). They were selected with the
      available random access method. Horizontal localization was evaluated with five
      speakers located at 0, +/-30, and +/-60 degree azimuths at a 1-meter distance
      from the examinee. Narrow-band noise signals were delivered at 35 dB SL in two
      "without earplug" and "with earplug" situations and the results were compared.
      The study was performed between September and December 2016 in Tehran, Iran.
      RESULTS: Significant differences were observed in localization errors between the
      "with earplug" and "without earplug" situations. The localization differences
      were greater for left-side speakers (-30 and -60 degrees) compared with right
      side speakers (+30 and +60 degrees). The differences were more apparent at 4,000
      and 6,000 Hz, which confirmed the effect of unilateral simulated hearing loss on
      interaural latency differences. CONCLUSIONS: Simulating hearing loss by using an
      earplug in one ear (right) increased localization errors at all frequencies. The
      errors increased at higher frequencies.

PMID- 29325393
TI  - Role of Emotional Distress in Prolongation of Dizziness: A Cross-Sectional Study.
AB  - BACKGROUND AND OBJECTIVES: Dizziness is a common condition in outpatient clinics.
      Comorbid conditions such as anxiety and/or depression often complicate a
      patient's ability to cope with dizziness. The purpose of the present study was to
      explore the extent of psychiatric distress using the Hospital Anxiety and
      Depression Scale (HADS) and to compare the results with the subjective severity
      of dizziness. SUBJECTS AND METHODS: The cross-sectional study included a total of
      456 consecutive patients presenting with acute (n=327) and chronic (n=127)
      dizziness symptoms. The HADS was used to estimate emotional distress and compare
      between patients with acute and chronic dizziness symptoms. Also, we calculated
      correlations between subjective dizziness handicap scores and emotional distress
      using the total and subscale scores of the Dizziness Handicap Inventory (DHI),
      Disability Scale (DS), and HADS. RESULTS: The HADS total and subscale scores were
      significantly increased in patients with chronic dizziness (p<0.01) compared with
      those with acute symptoms. In patients with symptoms of both acute and chronic
      dizziness, moderate correlations were evident between the DHI and HADS total
      scores. When we compared DHI subscale scores with the HADS scores, the emotional
      DHI subscale scores correlated more highly with the HADS total scores and the
      scores on the anxiety and depression subscales, than did the functional or
      physical DHI subscale scores. CONCLUSIONS: Increased levels of distress measured
      using the HADS in patients with chronic symptoms suggest that emotional status of
      the patients may contribute to prolongation of dizziness symptoms from the acute
      phase.

PMID- 29325394
TI  - Correction: Adverse effect of excess body weight on survival in cervical cancer
      patients after surgery and radiotherapy.
AB  - [This corrects the article on p. 48 in vol. 35.].

PMID- 29325395
TI  - Controversial issues in radiotherapy for rectal cancer: a systematic review.
AB  - The role of radiotherapy (RT) as an adjuvant to surgical options in the treatment
      of locally advanced rectal cancer has been established as it reduces local
      recurrence when combined with surgical resection and enhances survival when used
      in multidisciplinary treatment. However, many issues need to be addressed; some
      of these can render RT unnecessary, whereas others can reveal a new role of RT in
      rectal cancer. This review will discuss not only the basic role of RT but also
      the associated but controversial issues in detail in an attempt to find answers
      and determine future directions for the next decade.

PMID- 29325396
TI  - Treatment results of radiotherapy following CHOP or R-CHOP in limited-stage head
      and-neck diffuse large B-cell lymphoma: a single institutional experience.
AB  - PURPOSE: This study evaluated outcomes of radiotherapy (RT) after chemotherapy in
      limited-stage head-and-neck diffuse large B-cell lymphoma (DLBCL). MATERIALS AND
      METHODS: Eighty patients who were treated for limited-stage head-and-neck DLBCL
      with CHOP (n = 43) or R-CHOP (n = 37), were analyzed. After chemotherapy, RT was
      administered to the extended field (n = 60) or the involved field (n = 16), or
      the involved site (n = 4). The median dose of RT ranged from 36 Gy in case of
      those with a complete response, to 45-60 Gy in those with a partial response.
      RESULTS: In all patients, the 5-year overall survival (OS) and disease-free
      survival (DFS) rates were 83.9% and 80.1%, respectively. In comparison with the
      CHOP regimen, the R-CHOP regimen showed a better 5-year DFS (86.5% vs. 73.9%, p =
      0.027) and a lower rate of treatment failures (25.6% vs. 8.1%, p = 0.040). The
      volume (p = 0.047) and dose of RT (p < 0.001) were significantly reduced in
      patients treated with R-CHOP compared to that in those treated with CHOP.
      CONCLUSION: The outcomes of RT after chemotherapy with R-CHOP were better than
      those of CHOP regimen for limited-stage head-and-neck DLBCL. In patients treated
      with R-CHOP, a reduced RT dose and volume might be feasible without increasing
      treatment failures.

PMID- 29325398
TI  - Health Priorities in French-Speaking Swiss Cantons.
AB  - In Switzerland, the federal authorities, the cantons, and the communes share the
      responsibility of healthcare, disease prevention and health promotion policies.
      Yet, the cantons are in most health matters independent in their decisions, thus
      defining as a matter of fact their own health priorities. We examined and
      analysed the content of the disease prevention and health promotion plans
      elaborated during the last decade in six French-speaking cantons with different
      political contexts and resources, but quite similar population health data, in
      order to identify the set health priorities. The plans appear significantly
      inhomogeneous in their structure, scope and priorities. Most of the formal
      documents are short, in the 16 to 40 pages range. Core values such as equity,
      solidarity and sustainability are explicitly put forward in 2/6 cantonal plans.
      Priority health issues shared by all 6 cantons are "physical
      activity/sedentariness" and "nutrition/food." Mental health is explicitly
      mentioned in 5 cantonal plans, whereas tobacco and alcohol consumptions are
      mentioned 4 times. Less attention has been given to topics that appear as major
      public health challenges at present and in the future in Switzerland, eg, ageing
      of the population, rise of social inequalities, increase of vulnerable
      populations. Little attention has also been paid to issues like domestic violence
      or healthy work environments. Despite some heterogeneity, there is a common base
      that should make inter-cantonal collaborations possible and coordination with
      national strategies easily feasible.

PMID- 29325399
TI  - Evaluating the Process and Extent of Institutionalization: A Case Study of a
      Rapid Response Unit for Health Policy in Burkina Faso.
AB  - BACKGROUND: Good decision-making requires gathering and using sufficient
      information. Several knowledge translation platforms have been introduced in
      Burkina Faso to support evidence-informed decision-making. One of these is the
      rapid response service for health. This platform aims to provide quick access for
      policy-makers in Burkina Faso to highquality research evidence about health
      systems. The purpose of this study is to describe the process and extent of the
      institutionalization of the rapid response service. METHODS: A qualitative case
      study design was used, drawing on interviews with policy-makers, together with
      documentary analysis. Previously used institutionalization frameworks were
      combined to guide the analysis. RESULTS: Burkina Faso's rapid response service
      has largely reached the consolidation phase of the institutionalization process
      but not yet the final phase of maturity. The impetus for the project came from
      designated project leaders, who convinced policy-makers of the importance of the
      rapid response service, and obtained resources to run a pilot. During the
      expansion stage, additional policy-makers at national and sub-national levels
      began to use the service. Unit staff also tried to improve the way it was
      delivered, based on lessons learned during the pilot stage. The service has,
      however, stagnated at the consolidation stage, and not moved into the final phase
      of maturity. CONCLUSION: The institutionalization process for the rapid response
      service in Burkina Faso has been fluid rather than linear, with some areas
      developing faster than others. The service has reached the consolidation stage,
      but now requires additional efforts to reach maturity.

PMID- 29325397
TI  - Unequal Gain of Equal Resources across Racial Groups.
AB  - The health effects of economic resources (eg, education, employment, and living
      place) and psychological assets (eg, self-efficacy, perceived control over life,
      anger control, and emotions) are well-known. This article summarizes the results
      of a growing body of evidence documenting Blacks' diminished return, defined as a
      systematically smaller health gain from economic resources and psychological
      assets for Blacks in comparison to Whites. Due to structural barriers that Blacks
      face in their daily lives, the very same resources and assets generate smaller
      health gain for Blacks compared to Whites. Even in the presence of equal access
      to resources and assets, such unequal health gain constantly generates a racial
      health gap between Blacks and Whites in the United States. In this paper, a
      number of public policies are recommended based on these findings. First and
      foremost, public policies should not merely focus on equalizing access to
      resources and assets, but also reduce the societal and structural barriers that
      hinder Blacks. Policy solutions should aim to reduce various manifestations of
      structural racism including but not limited to differential pay, residential
      segregation, lower quality of education, and crime in Black and urban
      communities. As income was not found to follow the same pattern demonstrated for
      other resources and assets (ie, income generated similar decline in risk of
      mortality for Whites and Blacks), policies that enforce equal income and increase
      minimum wage for marginalized populations are essential. Improving quality of
      education of youth and employability of young adults will enable Blacks to
      compete for high paying jobs. Policies that reduce racism and discrimination in
      the labor market are also needed. Without such policies, it will be very
      difficult, if not impossible, to eliminate the sustained racial health gap in the
      United States.

PMID- 29325400
TI  - Eliminating Healthcare-Associated Infections in Iran: A Qualitative Study to
      Explore Stakeholders' Views.
AB  - BACKGROUND: Although preventable, healthcare-associated infections (HAIs)
      continue to pose huge health and economic burdens on countries worldwide. Some
      studies have indicated the numerous causes of HAIs, but only a tiny literature
      exists on the multifaceted measures that can be used to address the problem. This
      paper presents stakeholders' opinions on measures for controlling HAIs in Iran.
      METHODS: We used the qualitative research method in studying the phenomenon.
      Through a purposive sampling approach, we conducted 24 face-to-face interviews
      using a semi-structured interview guide. Participants were mainly key informants,
      including policy-makers, health professionals, and technical officers across the
      national and subnational levels, including the Ministry of Health (MoH), medical
      universities, and hospitals in Iran. We performed thematic framework analysis
      using the software MAXQDA10. RESULTS: Four main interdisciplinary themes emerged
      from our study of measures of controlling HAIs: strengthening governance and
      stewardship; strengthening human resources policies; appropriate prescription and
      usage of antibiotics; and environmental sanitation and personal hygiene.
      CONCLUSION: According to our findings, elimination of HAIs demands multifactorial
      interventions. While the ultimate recommendation of policy-makers is to have HAIs
      among the priorities of the national agenda, financial commitment and the
      creation of an enabling work environment in which both patients and healthcare
      workers can practice personal hygiene could lead to a significant reduction in
      HAIs in Iran.

PMID- 29325401
TI  - Performance-Based Financing to Strengthen the Health System in Benin: Challenging
      the Mainstream Approach.
AB  - BACKGROUND: Performance-based financing (PBF) is often proposed as a way to
      improve health system performance. In Benin, PBF was launched in 2012 through a
      World Bank-supported project. The Belgian Development Agency (BTC) followed suit
      through a health system strengthening (HSS) project. This paper analyses and
      draws lessons from the experience of BTC-supported PBF alternative approach -
      especially with regards to institutional aspects, the role of demand-side actors,
      ownership, and cost-effectiveness - and explores the mechanisms at stake so as to
      better understand how the "PBF package" functions and produces effects. METHODS:
      An exploratory, theory-driven evaluation approach was adopted. Causal mechanisms
      through which PBF is hypothesised to impact on results were singled out and
      explored. This paper stems from the co-authors' capitalisation of experiences;
      mixed methods were used to collect, triangulate and analyse information. Results
      are structured along Witter et al framework. RESULTS: Influence of context is
      strong over PBF in Benin; the policy is donor-driven. BTC did not adopt the World
      Bank's mainstream PBF model, but developed an alternative approach in line with
      its HSS support programme, which is grounded on existing domestic institutions.
      The main features of this approach are described (decentralised governance, peer
      review verification, counter-verification entrusted to health service users'
      platforms), as well as its adaptive process. PBF has contributed to strengthen
      various aspects of the health system and led to modest progress in utilisation of
      health services, but noticeable improvements in healthcare quality. Three
      mechanisms explaining observed outcomes within the context are described:
      comprehensive HSS at district level; acting on health workers' motivation through
      a complex package of incentives; and increased accountability by reinforcing
      dialogue with demand-side actors. Cost-effectiveness and sustainability issues
      are also discussed. CONCLUSION: BTC's alternative PBF approach is both promising
      in terms of effects, ownership and sustainability, and less resource consuming.
      This experience testifies that PBF is not a uniform or rigid model, and opens the
      policy ground for recipient governments to put their own emphasis and priorities
      and design ad hoc models adapted to their context specificities. However,
      integrating PBF within the normal functioning of local health systems, in line
      with other reforms, is a big challenge.

PMID- 29325402
TI  - Assessing Patient Organization Participation in Health Policy: A Comparative
      Study in France and Italy.
AB  - BACKGROUND: Even though there are many patient organizations across Europe, their
      role in impacting health policy decisions and reforms has not been well
      documented. In line with this, the present study endeavours to fill this gap in
      the international literature. To this end, it aims to validate further a
      previously developed instrument (the Health Democracy Index - HDI) measuring
      patient organization participation in health policy decision-making. In addition,
      by utilizing this tool, it aims to provide a snapshot of the degree and impact of
      cancer patient organization (CPO) participation in Italy and France. METHODS: A
      convenient sample of 188 members of CPOs participated in the study (95
      respondents from 10 CPOs in Italy and 93 from 12 CPOs in France). Participants
      completed online a self-reported questionnaire, encompassing the 9-item index and
      questions enquiring about the type and impact of participation in various facets
      of health policy decisionmaking. The psychometric properties of the scale were
      explored by performing factor analysis (construct validity) and by computing
      Cronbach alpha (internal consistency). RESULTS: Findings indicate that the index
      has good internal consistency and the construct it taps is unidimensional. The
      degree and impact of CPO participation in health policy decision-making were
      found to be low in both countries; however in Italy they were comparatively lower
      than in France. CONCLUSION: In conclusion, the HDI can be effectively used in
      international policy and research contexts. CPOs participation is low in Italy
      and France and concerted efforts should be made on upgrading their role in health
      policy decision-making.

PMID- 29325403
TI  - Economic Inequality in Presenting Vision in Shahroud, Iran: Two Decomposition
      Methods.
AB  - BACKGROUND: Visual acuity, like many other health-related problems, does not have
      an equal distribution in terms of socio-economic factors. We conducted this study
      to estimate and decompose economic inequality in presenting visual acuity using
      two methods and to compare their results in a population aged 40-64 years in
      Shahroud, Iran. METHODS: The data of 5188 participants in the first phase of the
      Shahroud Cohort Eye Study, performed in 2009, were used for this study. Our
      outcome variable was presenting vision acuity (PVA) that was measured using
      LogMAR (logarithm of the minimum angle of resolution). The living standard
      variable used for estimation of inequality was the economic status and was
      constructed by principal component analysis on home assets. Inequality indices
      were concentration index and the gap between low and high economic groups. We
      decomposed these indices by the concentration index and BlinderOaxaca
      decomposition approaches respectively and compared the results. RESULTS: The
      concentration index of PVA was -0.245 (95% CI: -0.278, -0.212). The PVA gap
      between groups with a high and low economic status was 0.0705 and was in favor of
      the high economic group. Education, economic status, and age were the most
      important contributors of inequality in both concentration index and Blinder
      Oaxaca decomposition. Percent contribution of these three factors in the
      concentration index and Blinder-Oaxaca decomposition was 41.1% vs. 43.4%, 25.4%
      vs. 19.1% and 15.2% vs. 16.2%, respectively. Other factors including gender,
      marital status, employment status and diabetes had minor contributions.
      CONCLUSION: This study showed that individuals with poorer visual acuity were
      more concentrated among people with a lower economic status. The main
      contributors of this inequality were similar in concentration index and Blinder
      Oaxaca decomposition. So, it can be concluded that setting appropriate
      interventions to promote the literacy and income level in people with low
      economic status, formulating policies to address economic problems in the
      elderly, and paying more attention to their vision problems can help to alleviate
      economic inequality in visual acuity.

PMID- 29325404
TI  - Recent Iranian Health System Reform: An Operational Perspective to Improve Health
      Services Quality.
AB  - The operational management of healthcare services is expected to directly touch
      patient experiences. Iranian Ministry of Health and Medical Education (MoHME) for
      the first time, as such, has sought to improve the operational management of
      healthcare delivery within a reform agenda by setting benchmarks for 'number of
      visit per hour' and waiting time in outpatient clinics of about 700 affiliated
      hospitals. As a new initiative, it has faced with mixed reactions and various
      doubts have been cast on its successful implementation. This manuscript aims to
      shed some light on the operational challenges of the initiative and the
      requirements of its successful implementation.

PMID- 29325405
TI  - WHO FCTC as a Pioneering and Learning Instrument Comment on "The Legal Strength
      of International Health Instruments - What It Brings to Global Health
      Governance?"
AB  - The World Health Organization (WHO) Framework Convention on Tobacco Control
      (FCTC) is a unique global health instrument, since it is in the health field the
      only instrument that is international law. After the 10 years of its existence an
      Independent Expert Group assessed the impact of the FCTC using all available data
      and visiting a number of countries interviewing different stakeholders. It is
      quite clear that the Treaty has acted as a strong catalyst and framework for
      national actions and that remarkable progress in global tobacco control can be
      seen. At the same time FCTC has moved tobacco control in countries from a pure
      health issue to a legal responsibility of the whole government, and on the
      international level created stronger interagency collaboration. The assessment
      also showed the many challenges. The spread of tobacco use, as well as of other
      risk lifestyles, is related to globalization. FCTC is a pioneering example of
      global action to counteract the negative social consequences of globalization. A
      convention is not an easy instrument, but the FCTC has undoubtedly sparked
      thinking and development of other stronger public health instruments and of
      needed governance structures.

PMID- 29325406
TI  - Polycentrism in Global Health Governance Scholarship Comment on "Four Challenges
      That Global Health Networks Face".
AB  - Drawing on an in-depth analysis of eight global health networks, a recent essay
      in this journal argued that global health networks face four challenges to their
      effectiveness: problem definition, positioning, coalition-building, and
      governance. While sharing the argument of the essay concerned, in this
      commentary, we argue that these analytical concepts can be used to explicate a
      concept that has implicitly been used in global health governance scholarship for
      quite a few years. While already prominent in the discussion of climate change
      governance, for instance, global health governance scholarship could make
      progress by looking at global health governance as being polycentric. Concisely,
      polycentric forms of governance mix scales, mechanisms, and actors. Drawing on
      the essay, we propose a polycentric approach to the study of global health
      governance that incorporates coalitionbuilding tactics, internal governance and
      global political priority as explanatory factors.

PMID- 29325407
TI  - The Bright Elusive Butterfly of Value in Health Technology Development Comment on
      "Providing Value to New Health Technology: The Early Contribution of
      Entrepreneurs, Investors, and Regulatory Agencies".
AB  - The current system of health technology development is characterised by multiple
      misalignments. The "supply" side (innovation policy-makers, entrepreneurs,
      investors) and the "demand" side (health policy-makers, regulators, health
      technology assessment, purchasers) operate under different - and conflicting -
      logics. The system is less a "pathway" than an unstable ecosystem of multiple
      interacting sub-systems. "Value" means different things to each of the numerous
      actors involved. Supply-side dynamics are built on fictions; regulatory checks
      and balances are designed to assure quality, safety and efficacy, not to ensure
      that technologies entering the market are either desirable or cost-effective.
      Assessment of comparative and cost-effectiveness usually comes too late in the
      process to shape an innovation's development. We offer no simple solutions to
      these problems, but in the spirit of commencing a much-needed public debate, we
      suggest some tentative ways forward. First, universities and public research
      funders should play a more proactive role in shaping the system. Second, the role
      of industry in forging long-term strategic partnerships for public benefit should
      be acknowledged (though not uncritically). Third, models of "responsible
      innovation" and public input to research priority-setting should be explored.
      Finally, the evidence base on how best to govern inter-sectoral health research
      partnerships should be developed and applied.

PMID- 29325408
TI  - Priority Setting: Right Answer to a Far Too Narrow Question? Comment on "Global
      Developments in Priority Setting in Health".
AB  - In their recent editorial, Baltussen and colleagues provide a concise summary of
      the prevailing discourse on priority-setting in health policy. Their perspective
      is entirely consistent with current practice, yet they unintentionally
      demonstrate the narrowness and moral precariousness of that discourse and
      practice. I respond with demonstrations of the importance of 'interrogating
      scarcity' in a variety of contexts.

PMID- 29325409
TI  - All Health Partnerships, Great and Small: Comparing Mandated With Emergent Health
      Partnerships Comment on "Evaluating Global Health Partnerships: A Case Study of a
      Gavi HPV Vaccine Application Process in Uganda".
AB  - The plurality of healthcare providers and funders in low- and middle-income
      countries (LMICs) has given rise to an era in which health partnerships are
      becoming the norm in international development. Whether mandated or emergent,
      three common drivers are essential for ensuring successful health partnerships:
      trust; a diverse and inclusive network; and a clear governance structure.
      Mandated and emergent health partnerships operate as very different models and at
      different scales. However, there is potential for sharing and learning between
      these types of partnerships. Emergent health partnerships, especially as they
      scale up, may learn from mandated partnerships about establishing clear
      governance mandates for larger and more complex partnerships. By combining social
      network analysis, which can detect key actors and stakeholders that could add
      value to existing emergent partnerships, with Brinkerhoff 's comprehensive
      framework for partnership evaluation, we can identify a set of tools that could
      be used to evaluate the effectiveness and sustainability of emergent health
      partnerships.

PMID- 29325410
TI  - Personalisation - An Emergent Institutional Logic in Healthcare? Comment on "(Re)
      Making the Procrustean Bed? Standardization and Customization as Competing Logics
      in Healthcare".
AB  - This commentary on the recent think piece by Mannion and Exworthy reviews their
      core arguments, highlighting their suggestion that recent forces for
      personalization have emerged which may counterbalance the strong standardization
      wave which has been evident in many healthcare settings and systems over the last
      two decades. These forces for personalization can take very different forms. The
      commentary explores the authors' suggestion that these themes can be fruitfully
      examined theoretically through an institutional logics (ILs) literature, which
      has recently been applied by some scholars to healthcare settings. This
      commentary outlines key premises of that theoretical tradition. Finally, the
      commentary makes suggestions for taking this IL influenced research agenda
      further, along with some issues to be addressed.

PMID- 29325411
TI  - Evidence-Informed Deliberative Processes - Early Dialogue, Broad Focus and
      Relevance: A Response to Recent Commentaries.

PMID- 29325412
TI  - Water-Assisted Hole Trapping at the Highly Curved Surface of Nano-TiO2
      Photocatalyst.
AB  - Heterogeneous photocatalysis is vital in solving energy and environmental issues
      that this society is confronted with. Although photocatalysts are often operated
      in the presence of water, it has not been yet clarified how the interaction with
      water itself affects charge dynamics in photocatalysts. Using water-coverage
      controlled steady and transient infrared absorption spectroscopy and large-model
      (~800 atoms) ab initio calculations, we clarify that water enhances hole trapping
      at the surface of TiO2 nanospheres but not of well-faceted nanoparticles. This
      water-assisted effect unique to the nanospheres originates from water adsorption
      as a ligand at a low-coordinated Ti-OH site or through robust hydrogen bonding
      directly to the terminal OH at the highly curved nanosphere surface. Thus, the
      interaction with water at the surface of nanospheres can promote photocatalytic
      reactions of both oxidation and reduction by elongating photogenerated carrier
      lifetimes. This morphology-dependent water-assisted effect provides a novel and
      rational basis for designing and engineering nanophotocatalyst morphology to
      improve photocatalytic performances.

PMID- 29325413
TI  - Direct Detection of Hardly Detectable Hidden Chirality of Hydrocarbons and
      Deuterated Isotopomers by a Helical Polyacetylene through Chiral Amplification
      and Memory.
AB  - We report the first direct chirality sensing of a series of chiral hydrocarbons
      and isotopically chiral compounds (deuterated isotopomers), which are almost
      impossible to detect by conventional optical spectroscopic methods, by a
      stereoregular polyacetylene bearing 2,2'-biphenol-derived pendants. The
      polyacetylene showed a circular dichroism due to a preferred-handed helix
      formation in response to the hardly detectable hidden chirality of saturated
      tertiary or chiroptical quaternary hydrocarbons, and deuterated isotopomers. In
      sharp contrast to the previously reported sensory systems, the chirality
      detection by the polyacetylene relies on an excess one-handed helix formation
      induced by the chiral hydrocarbons and deuterated isotopomers via significant
      amplification of the chirality followed by its static memory, through which
      chiral information on the minute and hidden chirality can be stored as an excess
      of a single-handed helix memory for a long time.

PMID- 29325414
TI  - Molecular Dynamics of Photoinduced Reactions of Acrylic Acid: Products,
      Mechanisms, and Comparison with Experiment.
AB  - The photochemistry of acrylic acid is of considerable atmospheric importance.
      However, the mechanisms and the time scales of the reactions involved are
      unknown. In this work, the products, yields, and reaction pathways of acrylic
      acid photochemistry are investigated theoretically by molecular dynamics
      simulations on the pipi* excited state. Two methods were used to describe the
      excited state: the semiempirical OM2/MRCI and the ab initio ADC(2). Over 100
      trajectories were computed with each method. A rich variety of reaction channels
      including mechanisms, time scales, and yields are predicted for the single
      potential energy surface used. Main findings include: (1) Products predicted by
      the calculations are in good agreement with experiments; (2) ADC(2) seems to
      validate OM2/MRCI predictions on main aspects of mechanisms, but not on time
      scales. It is concluded that both semiempirical and ab initio molecular dynamics
      simulations have useful advantages for the description of photochemical dynamics
      of carboxylic acids.

PMID- 29325415
TI  - Recrystallization of Manganite (gamma-MnOOH) and Implications for Trace Element
      Cycling.
AB  - The recrystallization of Mn(III,IV) oxides is catalyzed by aqueous Mn(II)
      (Mn(II)aq) during (bio)geochemical Mn redox cycling. It is poorly understood how
      trace metals associated with Mn oxides (e.g., Ni) are cycled during such
      recrystallization. Here, we use X-ray absorption spectroscopy (XAS) to examine
      the speciation of Ni associated with Manganite (gamma-Mn(III)OOH) suspensions in
      the presence or absence of Mn(II)aq under variable pH conditions (pH 5.5 and
      7.5). In a second set of experiments, we used a 62Ni isotope tracer to quantify
      the amount of dissolved Ni that exchanges with Ni incorporated in the Manganite
      crystal structure during reactions in 1 mM Mn(II)aq and in Mn(II)-free solutions.
      XAS spectra show that Ni is initially sorbed on the Manganite mineral surface and
      is progressively incorporated into the mineral structure over time (13% after 51
      days) even in the absence of dissolved Mn(II). The amount of Ni incorporation
      significantly increases to about 40% over a period of 51 days when Mn(II)aq is
      present in solution. Similarly, Mn(II)aq promotes Ni exchange between Ni
      substituted Manganite and dissolved Ni(II), with around 30% of Ni exchanged at pH
      7.5 over the duration of the experiment. No new mineral phases are detected
      following recrystallization as determined by X-ray diffraction and XAS. Our
      results reveal that Mn(II)-catalyzed mineral recrystallization partitions Ni
      between Mn oxides and aqueous fluids and can therefore affect Ni speciation and
      mobility in the environment.

PMID- 29325416
TI  - IgY Reduces AFB1-Induced Cytotoxicity, Cellular Dysfunction, and Genotoxicity in
      Human L-02 Hepatocytes and Swan 71 Trophoblasts.
AB  - Aflatoxin B1 (AFB1) causes hepatotoxic, genotoxic, and immunotoxic effects in a
      variety of species. Although various neutralizing agents of AFB1 toxicity have
      been studied, the egg yolk immunoglobulin (IgY) detoxification of small molecular
      toxins and the mechanisms underlying such effects have not yet been reported. In
      this investigation, anti-AFB1 IgY against AFB1 was successfully raised, and a
      competitive indirect enzyme-linked immunosorbent assay was established with a
      sensitive half-maximal inhibitory concentration (IC50, 2.4 ng/mL) and dynamic
      working range (0.13-43.0 ng/mL). The anti-AFB1 IgY obtained reduced AFB1-induced
      cytotoxicity, cellular dysfunction, and genotoxicity by protecting cells against
      apoptotic body formation and DNA strand breaks, preventing G2/M phase cell cycle
      arrest, reducing AFB1-DNA adduct and reactive oxygen species production and
      maintaining cell migration and invasion and the mitochondrial membrane potential.
      Anti-AFB1 IgY significantly inhibited the AFB1-induced expression of proteins
      related to antioxidative, pro-apoptotic, and antiapoptotic processes in a strong
      dose-dependent manner. These experiments demonstrated that the anti-AFB1 IgY
      bound AFB1 could not enter cells. This is the first time that IgY has been found
      to reduce the effects of small molecular toxins, which will be beneficial for the
      development of antibodies as detoxication agents.

PMID- 29325418
TI  - The Human Microbiome.

PMID- 29325417
TI  - Rhubarb Supplementation Promotes Intestinal Mucosal Innate Immune Homeostasis
      through Modulating Intestinal Epithelial Microbiota in Goat Kids.
AB  - The abuse and misuse of antibiotics in livestock production pose a potential
      health risk globally. Rhubarb can serve as a potential alternative to
      antibiotics, and several studies have looked into its anticancer, antitumor, and
      anti-inflammatory properties. The aim of this study was to test the effects of
      rhubarb supplementation to the diet of young ruminants on innate immune function
      and epithelial microbiota in the small intestine. Goat kids were fed with a
      control diet supplemented with or without rhubarb (1.25% DM) and were slaughtered
      at days 50 and 60 of age. Results showed that the supplementation of rhubarb
      increased ileal villus height (P = 0.036), increased jejujal and ileal anti
      inflammatory IL-10 production (P < 0.05), increased jejunal and ileal Claudin-1
      expression at both mRNA and protein levels (P < 0.05), and decreased ileal pro
      inflammatory IL-1beta production (P < 0.05). These changes in innate immune
      function were accompanied by shifts in ileal epithelial bacterial ecosystem in
      favor of Blautia, Clostridium, Lactobacillus, and Pseudomonas, and with a decline
      in the relative abundance of Staphylococcus (P < 0.001) when rhubarb was
      supplemented. Additionally, age also affected (P < 0.05) crypt depth, cytokine
      production, Claudin-1 expression and relative abundances of specific genera in
      epithelial bacteria. Collectively, the supplementation of rhubarb could enhance
      host mucosal innate immune homeostasis by modulating intestinal epithelial
      microbiota during the early stages of animal development.

PMID- 29325419
TI  - A new method of infrared-fluorescence-enhanced thoracoscopic segmentectomy.
AB  - Optimal identification of the intersegmental plane can be challenging during
      thoracoscopic anatomical segmentectomy for lung cancer. We describe a simple new
      method of infrared-fluorescence-enhanced thoracoscopy with selected injection of
      indocyanine green into the bronchi not targeted for resection, which allows us to
      clearly identify the intersegmental plane in thoracoscopic segmentectomy.

PMID- 29325420
TI  - Adolescent and caregivers' experiences of electronic adherence assessment in
      paediatric problematic severe asthma.
AB  - This study explored the experiences of adolescents and their caregivers regarding
      adherence to inhaled corticosteroids which are assessed through an electronic
      monitoring device (EMD). These devices are increasingly being used for assessing
      medication adherence, yet there is little information about patient's experience
      of these tools. Semi-structured interviews were conducted with eight adolescents
      with severe asthma, aged 11-15 years, who were electronically monitored as part
      of their care, along with their caregivers. Interviews were analysed using
      thematic analysis. Three themes were identified: 'they were trying to help me get
      better', 'checking up and catching out' and 'who is responsible?' The themes
      highlighted differences in priorities between participant groups, the impact of
      monitoring on the healthcare relationship and the dilemma of transferring
      responsibility for asthma management to adolescents. The findings suggest it is
      important for healthcare professionals to engage with patient's preferences and
      priorities when introducing EMDs.

PMID- 29325421
TI  - Effects of underwater bubble CPAP on very-low-birth-weight preterm newborns in
      the delivery room and after transport to the neonatal intensive care unit.
AB  - The development of less invasive ventilatory strategies in very-low-birth-weight
      (VLBW) preterm newborns has been a growing concern in recent decades. This study
      aimed to measure differences in the clinical progression of preterm newborns
      using two distinct periods in a university hospital: before and after using
      underwater bubble continuous positive airway pressure (ubCPAP). This is a
      retrospective study of VLBW preterm newborns with gestational ages less than or
      equal to 32 weeks admitted to the neonatal intensive care unit. The time series
      was divided into two groups: a pre-CPAP group ( n = 45) and a post-CPAP group ( n
      = 40). The post-CPAP group had fewer resuscitations, required fewer surfactant
      doses, spent fewer days on mechanical ventilation, and demonstrated less of a
      need for fraction of inspired oxygen > 30%. UbCPAP is an easy to use, minimally
      invasive, and effective ventilatory strategy for VLBW preterm newborns that can
      be used in environments with limited resources. Thus, adopting this simple
      strategy as part of a service organization and health policy can positively
      impact outcomes.

PMID- 29325423
TI  - Early Functional, Radiological Outcomes and Satisfaction Rates of Total Ankle
      Arthroplasty in an Asian Population.
AB  - BACKGROUND: Few studies have outlined the outcomes and complications in Asians
      undergoing total ankle arthroplasty. This study reports the functional,
      radiological outcomes and satisfaction rates in our Asian population. METHODS:
      Patients who underwent primary total ankle arthroplasty from 2007 to 2013 were
      recruited. Outcomes evaluated were the AOFAS Ankle-Hindfoot Score (AHS), Visual
      Analogue Scale (VAS), and the Short Form 36 (SF-36)questionnaire. Outcome scores
      were collected prospectively up to 2 years. Patient satisfaction was evaluated on
      a 6-point scale based on North American Spine Society Low Back Pain Instrument
      and classified as satisfied or unsatisfied. RESULTS: Forty-one patients underwent
      primary total ankle arthroplasty. All patients experienced improvements in AHS,
      VAS, and Mental Component Summary score of the SF-36 at both 6-month and 2-year
      postoperative interval. The mean AHS score improved from 35 +/- 19 points
      preoperatively to 64 +/- 24 at 6 months (P<.001) and 72 +/- 26 at 24 months (P
      <.001). VAS scores improved from 7 +/- 2 preoperatively to 3 +/- 3 (P < .001) at
      6 and 24 months. The Physical Component Summary (PCS) of the SF-36 has an
      established minimum clinically important difference (MCID) of 5. The mean
      improvement in PCS in our cohort met this MCID for the PCS; 63% and 71% of
      patients were satisfied with the procedure at 6 months and 2 years
      postoperatively, respectively. Revision rate in this series was 9.7%. CONCLUSION:
      Total ankle arthroplasty has good patient satisfaction rates, with favorable
      early clinical outcome in Asian patients. LEVELS OF EVIDENCE: Therapeutic, Level
      II.

PMID- 29325422
TI  - Outcomes in Deep Inferior Epigastric Perforator Flap and Implant-Based
      Reconstruction: Does Age Really Matter?
AB  - Despite the growing elderly population, there is limited research specific to
      this demographic concerning breast reconstruction (BR). Lack of evidence-based BR
      recommendations in older populations may contribute to misconceptions and
      subsequent underutilization of BR, especially autologous BR. Patients who
      received either deep inferior epigastric perforator (DIEP) flap BR or tissue
      expander/implant (TE/I) BR by a single surgeon between July 2011 and July 2015
      were surveyed postoperatively by using the psychometrically validated BREAST-Q
      questionnaire to determine patient satisfaction. Patients were categorized into
      younger and older cohorts based on median age (55 years) and further stratified
      based on the type of reconstruction. Of the 311 patients surveyed, 95 patients
      responded (31% response rate). Overall, younger patients (<55 years old, n = 42)
      compared with older patients (>=55 years old, n = 53) had significantly higher
      satisfaction with their outcome (mean difference [MD] 12.06; 95% confidence
      interval [CI]: 0.96-23.15; P = 0.034). In the TE/I group (n = 58), younger
      patients had significantly higher satisfaction with breasts (MD: 14.17; 95% CI:
      2.58-25.75; P = .017) and outcome (MD: 18.25; 95% CI: 3.95-32.5; P = .010) with
      fewer complications (odds ratio [OR]: 3.29; 95% CI: 1.37-7.86; P = .010). In the
      DIEP flap group (n = 55), there was no significant difference inr any of the
      satisfaction outcomes between younger and older patients. Younger patients tend
      to be more satisfied and demonstrate fewer complications with implant-based BR.
      In contrast, both younger and older patients undergoing abdominally based
      autologous BR were equally satisfied with comparable outcomes.

PMID- 29325424
TI  - Immediate Weight Bearing After Hallux Valgus Correction Using Locking Plate
      Fixation of the Ludloff Osteotomy: A Retrospective Review.
AB  - BACKGROUND: A Ludloff osteotomy is a common procedure used to correct hallux
      valgus deformities. Traditionally, the osteotomy is stabilized with screws only,
      thus requiring the patient to be non-weight bearing until healed. There have been
      no outcome studies analyzing immediate weight bearing after Ludloff osteotomy for
      hallux valgus. METHODS: Of the 350 patients (390 feet) who underwent a Ludloff
      osteotomy fixed with a locking plate and prescribed an immediate weight-bearing
      postoperative protocol, 288 patients (326 feet) were included in the analysis.
      Average radiographic follow-up was 8 months, and hallux-valgus angle (HVA),
      intermetatarsal angle (IMA), and any hardware failures or hypertrophic callus
      formation were recorded. The Foot Function Index (FFI) was assessed in 103
      patients at an average of 44 months postoperatively. RESULTS: Average IMA and HVA
      correction were 7.6 degrees  and 21.6 degrees , respectively (P < .0001). Loss of
      HVA and IMA correction of 4.6 degrees  and 2.3 degrees , respectively, were noted
      between the initial postoperative films and final weight-bearing films. The
      average FFI score calculated for the 103 respondents was 10.4 out of a possible
      100, indicating relatively low pain and disability. Complication rates were
      consistent with most other published postoperative protocols, with the most
      commonly seen being superficial infection (4.9%) and symptomatic hardware (4.6%).
      CONCLUSION: An immediate weight-bearing protocol for Ludloff osteotomies fixed
      with locking plates results in recurrence rates that are similar to those found
      with other protocols. Patient function is quite high and pain low following this
      protocol. The most commonly observed complications were superficial infection and
      symptomatic hardware requiring removal. LEVELS OF EVIDENCE: Level IV.

PMID- 29325425
TI  - Meningitis Vaccination, Knowledge, and Awareness Among YMSM in Chicago.
AB  - Serogroup C invasive meningococcal disease (IMD) outbreaks in men who have sex
      with men (MSM) have been occurring with greater frequency in urban areas across
      the United States. An effective vaccine for IMD is available and is recommended
      for MSM in outbreak settings. Particular subgroups of MSM have been
      disproportionately represented in outbreaks, specifically young, Black, and HIV
      positive MSM. As little is known about the knowledge, awareness, and vaccination
      status of young MSM, we sought to describe this and explore racial/ethnic
      differences. Data were collected from an established cohort study-RADAR-of 16- to
      29-year-old MSM recruited through previous cohort studies and/or by being a
      partner or peer of a current study member. A total of 486 young MSM (YMSM)
      responded to 13 IMD-related questions. Approximately half of the sample correctly
      identified how IMD is spread and 58.6% accurately responded that vaccination was
      the best prevention method; however, more than 60% of participants felt they were
      at no risk of getting meningitis and only 49% self-reported vaccination.
      Additionally, White YMSM were significantly more likely to be vaccinated and to
      have accurate knowledge and risk perception of IMD compared with Black YMSM.
      Findings have important implications for disease control, outbreak management,
      and intervention development.

PMID- 29325426
TI  - Naturally Occurring Mutations in HIV-1 CRF01_AE Capsid Affect Viral Sensitivity
      to Restriction Factors.
AB  - TRIM5alpha and MxB are known as restriction factors that inhibit the early step
      of intracellular HIV-1 replication cycle. Both factors are believed to interact
      with the incoming virus core to suppress HIV-1 infection. The extreme diversity
      of HIV-1 is thought to be a consequence of its propensity to mutate to escape
      immune responses and host restriction factors. We recently determined the capsid
      sequences for 144 HIV-1 CRF01_AE viruses obtained in Thailand from 2005 to 2011.
      In this study, we further analyzed the amino acid variations among the capsid
      sequences of 204 HIV-1 CRF01_AE obtained in Thailand and China, including 84 of
      the aforementioned 144 viruses, to detect mutations permitting escape from
      restriction by host factors. We found a characteristic combination of E79D, V83T,
      and H87Q in sequences from Chinese viruses and subsequently showed that this
      combination conferred partial resistance to MxB. Interestingly, this combination
      conferred resistance to human TRIM5alpha as well. The H87Q mutation alone
      conferred resistance to MxB in the CRF01_AE background, but not in subtype B
      virus. In contrast, the H87Q mutation alone conferred resistance to human
      TRIM5alpha in both the CFR01_AE and subtype B backgrounds. BLAST analysis
      revealed the presence of the E79D, V83T, and H87Q combination in CRF01_AE viruses
      isolated not only in China but also in many other countries. Although the
      mechanistic details as well as precise role of MxB antiviral activity in infected
      individuals remain to be clarified, our data suggest an interaction between MxB
      and the HIV-1 capsid in vivo.

PMID- 29325428
TI  - Mother-Child Coregulation of Parasympathetic Processes Differs by Child
      Maltreatment Severity and Subtype.
AB  - Parasympathetic processes appear to underlie maladaptive parent-child
      interactions in maltreating families, but it is unknown whether parent-child
      coregulation of respiratory sinus arrhythmia (RSA) differs by child maltreatment
      severity and subtype. RSA coregulation in maltreating and nonmaltreating mother
      child dyads ( N = 146; age 3-5 years) during two dyadic tasks was analyzed using
      dynamic time series modeling. Nonmaltreating dyads showed positive RSA
      concordance but maltreating dyads (when examined as one group) did not. However,
      when examined separately by subtype, physically abusive dyads showed positive
      concordance and neglectful dyads no concordance, in dyadic RSA. Patterns were
      further modified by maltreatment severity, which predicted discordant RSA (one
      partner's RSA predicting decreases in the other's) in both groups. Specifically,
      higher physical abuse severity predicted lower resting child RSA, declining
      mother RSA over time, and mother RSA predicting declines in child RSA over time,
      suggesting a mother-driven dyadic stress response. Higher neglect severity
      predicted increasing child RSA over time and child RSA predicting declines in
      mother RSA over time, suggesting a child-driven maternal stress response. These
      findings show there are distinct patterns of RSA coregulation in nonmaltreating,
      physically abusive, and neglectful mother-child dyads, which may inform etiology
      and intervention with respect to stress regulation in maltreating families.

PMID- 29325429
TI  - A Novel Method for Repositioning Suboptimally Preoperatively Placed Nephrostomy
      Tubes for Percutaneous Nephrolithotomy Without Renal Repuncture.
AB  - OBJECTIVE: Nephrostomy tubes (NTs) inserted in emergency settings by
      interventional radiologists are frequently unsuitable for subsequent percutaneous
      nephrolithotomy (PCNL). We report a novel method of adjusting these NTs to be
      used as PCNL tracts and avoid renal repuncture. PATIENTS AND METHODS: A
      retrospective search of 981 consecutive PCNLs performed in our institution
      between 2002 and 2017 identified all patients with preoperatively inserted NTs.
      The NTs unsuitable for PCNL were adjusted by a novel approach in which a 5-mm
      incision was made at the ideal puncture location (IPL) as indicated under
      fluoroscopic guidance. The preinserted NT was removed after passing a guidewire
      into the kidney. A dissector clamp was introduced through the entry wound of the
      removed NTs to bluntly dissect a retroperitoneal tunnel and pull out the distal
      tip of guidewire through the IPL, while its proximal segment was maintained in
      the kidney. The newly positioned guidewire was used for PCNL tract preparation
      without repuncturing the kidney. RESULTS: The NTs were located in the mid calix,
      lower calix, and renal pelvis in 6 (26%), 13 (57%), and 4 (17%) cases,
      respectively. The NT was suitable for PCNL in 5 (22%) cases, a new renal access
      was performed in 3 (13%), and the novel adjustment approach was used in 15 (65%),
      all successfully. The place of entry was moved an average of 6 cm (range 47) and
      the angle between the tract axis and the calix axis was reduced by 65 degrees  in
      average. The procedure was done uneventfully in an average of 4 minutes.
      CONCLUSIONS: The novel method of adjusting preoperatively inserted NTs for PCNL
      by repositioning their original entry location to the IPL offers the possibility
      of avoiding kidney repuncture. It is feasible, safe, and easy to implement, and
      it spares potential morbidity related to additional puncturing of the kidney.

PMID- 29325427
TI  - A Randomized Trial of Home Visitation for CPS-Involved Families: The Moderating
      Impact of Maternal Depression and CPS History.
AB  - Home visitation (HV) interventions may hold promise to improve parenting and
      prevent child maltreatment recidivism in families reported to child protective
      services (CPS) with young children, but this has rarely been studied. Findings
      are presented from an 18-month randomized controlled trial in which intact
      families ( N = 122) with at least one CPS report were provided with a facilitated
      connection to a paraprofessional evidence-based HV program or usual care services
      from child protection. Results are reported for changes in maternal stress,
      depression, and social support outcomes and repeat reports to CPS. No significant
      changes were found in maternal outcomes by group. Among nondepressed mothers or
      families without multiple CPS reports prior to study enrollment, HV was
      associated with a significantly lower likelihood of CPS report recidivism. These
      results indicate potential for HV to prevent maltreatment recidivism but suggest
      that higher intensity intervention is warranted for mothers exhibiting
      significant depressive symptoms or families with extensive CPS histories.

PMID- 29325431
TI  - Persons living with diagnosed HIV in New York City: over 50% over 50 years old.
AB  - Using NYC HIV surveillance data, we estimated the annual median age of persons
      living with diagnosed HIV (PLWDH) and the proportion of PLWDH over 50 years old
      in NYC between 2008 and 2015, and described the characteristics, retention in
      care and viral suppression status among PLWDH in NYC in 2015, by age (<50 vs.
      >=50 years old). The median age of PLWDH in NYC increased from 46.4 years
      (interquartile range [IQR]: 39.4, 53.2) in 2008 to 50.2 years (IQR: 39.8, 57.5)
      in 2015, and the proportion of PLWDH over 50 years old increased from 35.9% in
      2008 to 50.6% in 2015. In 2015, by race/ethnicity, whites had the highest
      proportion over 50 years old (57.0%) and Asian/Pacific Islanders had the lowest
      (36.2%); by transmission risk, men who have sex with men were the lowest (40.0%)
      and injection drug users were the highest (76.1%). A large and increasing
      proportion of PLWDH over 50 years old presents challenges for HIV-infected
      individuals and healthcare system. Better social support services for HIV
      infected individuals and additional training for medical and public health staff
      are needed.

PMID- 29325432
TI  - Risk Factors for Primary Failure of Metallic Ureteral Stents: Experience from a
      Tertiary Center.
AB  - INTRODUCTION: We provide primary patency rate of metallic ureteral stents in
      cancer patients and investigate the factors affecting primary patency. METHODS:
      All cancer patients who had received metallic stents for malignant ureteral
      obstruction between July 2009 and November 2012 in our institute were included.
      No patients were excluded. Patient profiles, imaging studies, and laboratory data
      were collected. Patient profiles included age, gender, body height, body weight,
      body mass index, cancer types, treatment for cancer, response to cancer
      treatment, methods of stent insertion, and prior ordinary stents. Imaging studies
      included renal ultrasonography, antegrade pyelography, CT, and MRI. Laboratory
      data included urinalysis, urine culture, and serum creatinine. Complications were
      defined according to the Clavien-Dindo classification. Primary patency was
      defined as a complete resolution or downgrading of hydronephrosis shown by
      imaging studies or success in the removal of a preexisting nephrostomy tube;
      otherwise the procedure was considered a primary failure. The primary endpoint
      was the primary patency rate of the stents. The secondary endpoints were risk
      factors for primary stent failure. RESULTS: A total of 124 stents were inserted
      into 96 patients with malignant ureteral obstruction. There were no grade 3/4
      complications. The overall primary patency rate was 87.9% (109/124). In
      univariate analysis, antegrade insertion (OR = 24.15, p-value = 0.0086) and
      urinary tract cancer (OR = 4.18, p-value = 0.0164) were significantly associated
      with primary failure. Those with prior ordinary stents (OR = 0.20, p-value =
      0.0158) or response to cancer treatment (OR = 0.25, p-value = 0.0228) were
      associated with stent patency. In multivariate analysis, antegrade insertion (OR
      = 22.04, p-value = 0.0041) and response to cancer treatment (OR = 0.15, p-value =
      0.01081) remained significant factors. CONCLUSIONS: In this large cohort of
      cancer patients requiring urinary diversion to preserve renal function, several
      factors were associated with the success rate of metallic stents.

PMID- 29325430
TI  - Rapid and Sensitive Assessment of Globin Chains for Gene and Cell Therapy of
      Hemoglobinopathies.
AB  - The beta-hemoglobinopathies sickle cell anemia and beta-thalassemia are the focus
      of many gene-therapy studies. A key disease parameter is the abundance of globin
      chains because it indicates the level of anemia, likely toxicity of excess or
      aberrant globins, and therapeutic potential of induced or exogenous beta-like
      globins. Reversed-phase high-performance liquid chromatography (HPLC) allows
      versatile and inexpensive globin quantification, but commonly applied protocols
      suffer from long run times, high sample requirements, or inability to separate
      murine from human beta-globin chains. The latter point is problematic for in vivo
      studies with gene-addition vectors in murine disease models and mouse/human
      chimeras. This study demonstrates HPLC-based measurements of globin expression
      (1) after differentiation of the commonly applied human umbilical cord blood
      derived erythroid progenitor-2 cell line, (2) in erythroid progeny of CD34+ cells
      for the analysis of clustered regularly interspaced short palindromic
      repeats/Cas9-mediated disruption of the globin regulator BCL11A, and (3) of
      transgenic mice holding the human beta-globin locus. At run times of 8 min for
      separation of murine and human beta-globin chains as well as of human gamma
      globin chains, and with routine measurement of globin-chain ratios for 12 nL of
      blood (tested for down to 0.75 nL) or of 300,000 in vitro differentiated cells,
      the methods presented here and any variant-specific adaptations thereof will
      greatly facilitate evaluation of novel therapy applications for beta
      hemoglobinopathies.

PMID- 29325433
TI  - Mental Health-Ill Health Differences in Disease Severity and Its Sociodemographic
      Biobehavioral Predictors Among Patients With Knee Osteoarthritis.
AB  - Our aim in this cross-sectional study was to investigate mental health-ill health
      differences in disease severity and its sociodemographic biobehavioral predictors
      among patients with knee osteoarthritis (OA). Applying convenient sampling, 180
      patients with knee OA in Tabriz, Iran, were recruited to participate in
      completing a three-section questionnaire (SF-12, Lequesne Algofunctional Index
      and Self-Management Behaviors Scale). Separate hierarchical multiple linear
      regressions were performed with OA severity as dependent variable: one for OA
      patients with positive mental health and other for OA patients with mental
      disorders symptoms. Among the patients with positive mental health, but not those
      with symptoms of mental disorder, pain management, duration of OA, physical
      activity management, living alone, and level of education were significant
      predictors of disease severity. Health care providers with a better understanding
      on the determinants of disease severity by mental health status may identify
      vulnerable patients and develop targeted interventions to foster disease
      management behaviors among OA patients.

PMID- 29325434
TI  - Collection of real-world data on nivolumab's effectiveness in renal cell
      carcinoma: rationale for an observational study.
AB  - Renal cell carcinoma (RCC) represents the seventh (men) respectively tenth
      (women) most frequent cancer in western countries. After one or more lines of
      VEGF-targeted therapy, immunotherapy with nivolumab is strongly recommended in
      patients with metastatic RCC. Nivolumab is the first, and so far, only approved
      PD-1 immune checkpoint inhibitor to demonstrate a gain in overall survival in
      RCC. We describe herein design and rationale of trial CA209653 ('NIS NORA'), a
      prospective, noninterventional cohort study investigating the effectiveness of
      nivolumab. This systematic collection of real-world effectiveness data will
      recruit 323 patients with advanced RCC to provide a precise estimate for overall
      survival over a 5-year follow-up period (Trial registration: NCT02940639).

PMID- 29325435
TI  - Early stages of HIV treatment cascade in people living with HIV in Saint
      Petersburg, Russia.
AB  - The proportion of people living with HIV (PLWH) in need of antiretroviral therapy
      (ART) is growing rapidly in Russia. Successful treatment outcomes reduces disease
      progression and contributes to HIV epidemic control. We conducted a pilot study
      following 100 PLWH newly found eligible for ART in St. Petersburg, Russia. We
      determined the proportion of PLWH who initiated ART, remained in treatment, and
      achieved an undetectable VL during 6-month follow up. Semi-structured interviews
      were conducted prior the initiation of ART and progress along the cascade was
      assessed through medical chart review. Individual characteristics associated with
      successful ART outcomes were assessed as part of efforts to generate hypotheses.
      Almost all (96%) participants initiated ART, full retention was demonstrated by
      80%, among whom 71% achieved undetectable VL. Optimal retention was associated
      with older age and higher education (p < 0.05). There was no significant
      difference in ART outcomes between those who used illicit drugs and those had
      not. Interventions to improve treatment effectiveness should emphasize that
      initiation, optimal retention and achieving an undetectable VL are independent of
      drug abuse status. However, our pilot study highlights the need for the further
      research in the examining links between individual and structural factors and ART
      effectiveness.

PMID- 29325436
TI  - Patient predictors of response to cognitive behaviour therapy and schema therapy
      for depression.
AB  - OBJECTIVE: Few studies have examined differential predictors of response to
      psychotherapy for depression. Greater understanding about the factors associated
      with therapeutic response may better enable therapists to optimise response by
      targeting therapy for the individual. The aim of the current exploratory study
      was to examine patient characteristics associated with response to cognitive
      behaviour therapy and schema therapy for depression. METHODS: Participants were
      100 outpatients in a clinical trial randomised to either cognitive behaviour
      therapy or schema therapy. Potential predictors of response examined included
      demographic, clinical, functioning, cognitive, personality and neuropsychological
      variables. RESULTS: Individuals with chronic depression and increased levels of
      pre-treatment negative automatic thoughts had a poorer response to both cognitive
      behaviour therapy and schema therapy. A treatment type interaction was found for
      verbal learning and memory. Lower levels of verbal learning and memory impairment
      markedly impacted on response to schema therapy. This was not the case for
      cognitive behaviour therapy, which was more impacted if verbal learning and
      memory was in the moderate range. CONCLUSION: Study findings are consistent with
      the Capitalisation Model suggesting that therapy that focuses on the person's
      strengths is more likely to contribute to a better outcome. Limitations were that
      participants were outpatients in a randomised controlled trial and may not be
      representative of other depressed samples. Examination of a variety of potential
      predictors was exploratory and requires replication.

PMID- 29325437
TI  - The prevalence and burden of mental and substance use disorders in Australia:
      Findings from the Global Burden of Disease Study 2015.
AB  - OBJECTIVES: Timely and accurate assessments of disease burden are essential for
      developing effective national health policies. We used the Global Burden of
      Disease Study 2015 to examine burden due to mental and substance use disorders in
      Australia. METHODS: For each of the 20 mental and substance use disorders
      included in Global Burden of Disease Study 2015, systematic reviews of
      epidemiological data were conducted, and data modelled using a Bayesian meta
      regression tool to produce prevalence estimates by age, sex, geography and year.
      Prevalence for each disorder was then combined with a disorder-specific
      disability weight to give years lived with disability, as a measure of non-fatal
      burden. Fatal burden was measured as years of life lost due to premature
      mortality which were calculated by combining the number of deaths due to a
      disorder with the life expectancy remaining at the time of death. Disability
      adjusted life years were calculated by summing years lived with disability and
      years of life lost to give a measure of total burden. Uncertainty was calculated
      around all burden estimates. RESULTS: Mental and substance use disorders were the
      leading cause of non-fatal burden in Australia in 2015, explaining 24.3% of total
      years lived with disability, and were the second leading cause of total burden,
      accounting for 14.6% of total disability-adjusted life years. There was no
      significant change in the age-standardised disability-adjusted life year rates
      for mental and substance use disorders from 1990 to 2015. CONCLUSION: Global
      Burden of Disease Study 2015 found that mental and substance use disorders were
      leading contributors to disease burden in Australia. Despite several decades of
      national reform, the burden of mental and substance use disorders remained
      largely unchanged between 1990 and 2015. To reduce this burden, effective
      population-level preventions strategies are required in addition to effective
      interventions of sufficient duration and coverage.

PMID- 29325438
TI  - Workplace ostracism And workplace behaviors: A moderated mediation model of
      perceived stress and psychological empowerment.
AB  - BACKGROUND AND OBJECTIVES: Workplace ostracism research has examined numerous
      underlying mechanisms to understand the link between workplace ostracism and
      behavioral outcomes. Ostracism has been suggested to be an interpersonal
      stressor; however, research has not investigated workplace ostracism from a
      stress perspective. Therefore, the study investigated the mediating effect of
      perceived stress for the relationships between workplace ostracism and helping
      behavior, voicing behavior, and task performance. The study also investigated the
      moderating effect of psychological empowerment for the relationships between
      perceived stress and behavioral outcomes. DESIGN: The study design was a three
      wave self-reported questionnaire. METHOD: The study sampled 225 full-time
      employees in South Korea and regression analyses with bootstrapping were
      conducted to test the moderated mediation models. RESULTS: The bootstrapped 95%
      CI around the indirect effects did not contain zero; therefore, perceived stress
      mediated the relationship between workplace ostracism and helping behavior (
      .06), voicing behavior (-.07), and task performance (-.07). Further, the
      moderated mediation analyses found perceived stress mediated the relationships
      between workplace ostracism and behavioral outcomes only when individuals
      perceived low levels of psychological empowerment. CONCLUSION: The findings
      suggest that workplace ostracism is a stressor and psychological empowerment can
      mitigate the negative effects of ostracism on behavioral outcomes.

PMID- 29325439
TI  - Quit Outcomes and Program Utilization by Mode of Entry Among Clients Enrolling in
      a Quitline.
AB  - PURPOSE: To investigate how mode of entry into a quitline influences program
      utilization and quit outcomes among clients seeking cessation services. DESIGN:
      This is a retrospective analysis of clients receiving quitline services from
      January 2011 to June 2016. SETTING: The study was conducted at the Arizona
      Smokers' Helpline. PARTICIPANTS: Enrolled clients completed a 7-month follow-up
      (N = 18 650). MEASURES: The independent variable was referral mode of entry (ie,
      proactive, passive, and self-referral). Outcome variables included tobacco
      cessation medication use, number of coaching sessions completed, and 30-day
      tobacco abstinence at 7 months. ANALYSIS: Logistic regression was used to analyze
      tobacco abstinence after controlling for potential confounders. RESULTS: Compared
      to self-referred clients, proactively referred clients were least likely (odds
      ratio [OR]: 0.88; 95% confidence interval [CI]: 0.81-0.97), whereas passively
      referred clients were most likely (OR: 1.14; 95% CI: 1.00-1.30) to report tobacco
      abstinence. Proactively referred (OR: 0.79; 95% CI: 0.70-0.88), but not passively
      referred, clients were 21% less likely to report tobacco cessation medication use
      than self-referred clients. CONCLUSION: Proactive referrals are associated with
      lower utilization of tobacco cessation medication and less successful quit
      outcomes; however, provider referrals are critical to reaching tobacco users who
      may have more significant health risks and barriers to quitting. Examining
      potential barriers among both providers and provider-referred clients is needed
      to inform improvements in training providers on brief interventions for tobacco
      cessation.

PMID- 29325442
TI  - Pooled Generation of Lentiviral Tetracycline-Regulated microRNA Embedded Short
      Hairpin RNA Libraries.
AB  - Short hairpin RNA (shRNA) screens are powerful tools to probe genetic
      dependencies in loss-of-function studies, such as the identification of
      therapeutic targets in cancer research. Lentivirally delivered shRNAs embedded in
      endogenous microRNA contexts (shRNAmiRs) mediate efficient long-term suppression
      of target genes suitable for numerous experimental contexts and clinical
      applications. Here, an easy-to-use laboratory protocol is described, covering the
      design and pooled assembly of focused shRNAmiR libraries into an optimized, Tet
      inducible all-in-one lentiviral vector, packaging of viral particles, followed by
      retrieval and quantification of hairpin sequences after cellular DNA-recovery.
      Starting from a gene list to the identification of hits, the protocol enables
      shRNA screens within 6 weeks.

PMID- 29325440
TI  - Case-Mix Adjustment of the Bereaved Family Survey.
AB  - Surveys of bereaved family members are increasingly being used to evaluate end-of
      life (EOL) care and to measure organizational performance in EOL care quality.
      The Bereaved Family Survey (BFS) is used to monitor EOL care quality and
      benchmark performance in the Veterans Affairs (VA) health-care system. The
      objective of this study was to develop a case-mix adjustment model for the BFS
      and to examine changes in facility-level scores following adjustment, in order to
      provide fair comparisons across facilities. We conducted a cross-sectional
      secondary analysis of medical record and survey data from veterans and their
      family members across 146 VA medical centers. Following adjustment using model
      based propensity weighting, the mean change in the BFS-Performance Measure score
      across facilities was -0.6 with a range of -2.6 to 0.6. Fifty-five (38%)
      facilities changed within +/-0.5 percentage points of their unadjusted score. On
      average, facilities that benefited most from adjustment cared for patients with
      greater comorbidity burden and were located in urban areas in the Northwest and
      Midwestern regions of the country. Case-mix adjustment results in minor changes
      to facility-level BFS scores but allows for fairer comparisons of EOL care
      quality. Case-mix adjustment of the BFS positions this National Quality Forum
      endorsed measure for use in public reporting and internal quality dashboards for
      VA leadership and may inform the development and refinement of case-mix
      adjustment models for other surveys of bereaved family members.

PMID- 29325441
TI  - Five-Year Experience of an Inpatient Palliative Care Unit at an Academic Referral
      Center.
AB  - BACKGROUND: Palliative care units (PCUs) staffed by specialty-trained physicians
      and nurses have been established in a number of medical centers. The purpose of
      this study is to review the 5-year experience of a PCU at a large, urban academic
      referral center. METHODS: We retrospectively reviewed a prospectively collected
      database of all admissions to the PCU at Vanderbilt University Medical Center in
      the first 5 years of its existence, from 2012 through 2017. RESULTS: Over these 5
      years, there were 3321 admissions to the PCU. No single underlying disease
      process accounted for the majority of the patients, but the largest single
      category of patients were those with malignancy, who accounted for 38% of
      admissions. Transfers from the intensive care unit accounted for 50% of
      admissions, with 43% of admissions from a hospital floor and 7% coming from the
      emergency department or a clinic. Median length of stay in the PCU was 3 days. In
      hospital deaths occurred for 50% of admitted patients, while 38% of patients were
      discharged from the PCU to hospice. CONCLUSION: These data show that a successful
      PCU is enabled by buy in from a wide variety of referring specialists and by a
      multidisciplinary palliative care team focused on care of the actively dying
      patient as well as pain and symptom management, advance care planning, and
      hospice referral since a large proportion of referred patients do not die in
      house.

PMID- 29325443
TI  - Moving upstream in health promoting policies for older people with early frailty
      in England? A policy analysis.
AB  - Objectives Globally, populations are rapidly ageing and countries have developed
      health promotion and wellbeing strategies to address increasing demand for health
      care and old-age support. The older population is not homogeneous however, and
      includes a large group in transition between being active and healthy to being
      frail, i.e. with early frailty. This review explores the extent to which policy
      in England has addressed this group with a view to supporting independence and
      preventing further progression towards frailty. Methods A narrative review was
      conducted of 157 health and social care policy documents current in 2014-2017 at
      three levels of the health and social care system in England. Findings We report
      the policy problem analysis, the shifts over time in language from health
      promotion to illness prevention, the shift in target populations to mid-life and
      those most at risk of adverse outcomes through frailty, and changes to delivery
      mechanisms to incentivize attention to the frailest rather than those with early
      frailty. We found that older people in general were not identified as a specific
      population in many of these policies. While this may reflect a welcome lack of
      age discrimination, it could equally represent omission through ageism. Only at
      local level did we identify some limited attention to preventative actions with
      people with early frailty. Conclusion The lack of policy attention to older
      people with early frailty is a missed opportunity to address some of the demands
      on health and social care services. Addressing the individual and societal
      consequences of adverse experiences of those with the greatest frailty should not
      distract from a more distinct public health perspective which argues for a
      refocusing upstream to health promotion and illness prevention for those with
      early frailty.

PMID- 29325445
TI  - The Morbidity of Ureteral Strictures in Patients with Prior Ureteroscopic Stone
      Surgery: Multi-Institutional Outcomes.
AB  - PURPOSE: Nephrolithiasis is an increasingly common ailment in the United States.
      Ureteroscopic management has supplanted shockwave lithotripsy as the most common
      treatment of upper tract stone disease. Ureteral stricture is a rare but serious
      complication of stone disease and its management. The impact of new technologies
      and more widespread ureteroscopic management on stricture rates is unknown. We
      describe our experience in managing strictures incurred following ureteroscopy
      for upper tract stone disease. MATERIALS AND METHODS: Records for patients
      managed at four tertiary care centers between December 2006 and October 2015 with
      the diagnosis of ureteral stricture following ureteroscopy for upper tract stone
      disease were retrospectively reviewed. Study outcomes included number and type
      (endoscopic, reconstructive, or nephrectomy) of procedures required to manage
      stricture. RESULTS: Thirty-eight patients with 40 ureteral strictures following
      URS for upper tract stone disease were identified. Thirty-five percent of
      patients had hydronephrosis or known stone impaction at the time of initial URS,
      and 20% of cases had known ureteral perforation at the time of initial URS. After
      stricture diagnosis, the mean number of procedures requiring sedation or general
      anesthesia performed for stricture management was 3.3 +/- 1.8 (range 1-10).
      Eleven strictures (27.5%) were successfully managed with endoscopic techniques
      alone, 37.5% underwent reconstruction, 10% had a chronic stent/nephrostomy, and
      10 (25%) required nephrectomy. CONCLUSIONS: The surgical morbidity of ureteral
      strictures incurred following ureteroscopy for stone disease can be severe, with
      a low success rate of endoscopic management and a high procedural burden that may
      lead to nephrectomy. Further studies that assess specific technical risk factors
      for ureteral stricture following URS are needed.

PMID- 29325446
TI  - Reduction of PTSD Symptoms With Pre-Reactivation Propranolol Therapy: A
      Randomized Controlled Trial.
AB  - OBJECTIVE: The authors assessed the efficacy of trauma memory reactivation
      performed under the influence of propranolol, a noradrenergic beta-receptor
      blocker, as a putative reconsolidation blocker, in reducing symptoms of
      posttraumatic stress disorder (PTSD). METHOD: This was a 6-week, double-blind,
      placebo-controlled, randomized clinical trial in 60 adults diagnosed with long
      standing PTSD. Propranolol or placebo was administered 90 minutes before a brief
      memory reactivation session, once a week for 6 consecutive weeks. The hypothesis
      predicted a significant treatment effect of trauma reactivation with propranolol
      compared with trauma reactivation with placebo in reducing PTSD symptoms on both
      the Clinician-Administered PTSD Scale (CAPS) and the patient-rated PTSD Checklist
      Specific (PCL-S) in an intention-to-treat analysis. RESULTS: The estimated group
      difference in posttreatment CAPS score, adjusted for pretreatment values
      (analysis of covariance), was a statistically significant 11.50. The within-group
      pre- to posttreatment effect sizes (Cohen's d) were 1.76 for propranolol and 1.25
      for placebo. For the PCL-S, the mixed linear model's estimated time-by-group
      interaction yielded an average decrease of 2.43 points per week, for a total
      significant difference of 14.58 points above that of placebo. The pre- to
      posttreatment effect sizes were 2.74 for propranolol and 0.55 for placebo. Per
      protocol analyses for both outcomes yielded similar significant results.
      CONCLUSIONS: Pre-reactivation propranolol, a treatment protocol suggested by
      reconsolidation theory, appears to be a novel and efficacious treatment for PTSD.
      Replication studies using a long-term follow-up in various trauma populations are
      required.

PMID- 29325447
TI  - Longitudinal Association of Amyloid Beta and Anxious-Depressive Symptoms in
      Cognitively Normal Older Adults.
AB  - OBJECTIVE: To understand the role of depressive symptoms in preclinical
      Alzheimer's disease, it is essential to define their temporal relationship to
      Alzheimer's proteinopathies in cognitively normal older adults. The study
      objective was to examine associations of brain amyloid beta and longitudinal
      measures of depression and depressive symptom clusters in a cognitively normal
      sample of older adults. METHOD: A total of 270 community-dwelling, cognitively
      normal elderly individuals underwent baseline Pittsburgh compound B (PiB)
      positron emission tomography (PET) measures of cortical aggregate amyloid beta
      and annual assessments with the 30-item Geriatric Depression Scale (GDS). The
      authors evaluated continuous PiB binding as a predictor of GDS score or GDS
      cluster, calculated as total scores and mean scores for three GDS item clusters
      (apathy-anhedonia, dysphoria, and anxiety-concentration), across time (1-5 years;
      mean=3.8 years) in separate mixed-effects models with backward elimination.
      Initial predictors included PiB binding, age, sex, Hollingshead score, American
      National Adult Reading Test (AMNART) score, apolipoprotein E epsilon4 status,
      depression history, and their interactions with time. RESULTS: Higher PiB binding
      predicted accelerated rates of increase in GDS score over time, adjusting for
      depression history. Higher PiB binding also predicted steeper rates of increase
      for anxiety-concentration scores, adjusting for depression history and the AMNART
      score-by-time interaction. In a post hoc model estimating anxiety scores without
      concentration disturbance items, the PiB binding-by-time interaction remained
      significant. CONCLUSIONS: Higher amyloid beta burden was associated with
      increasing anxious-depressive symptoms over time in cognitively normal older
      individuals. Prior depression history was related to higher but not worsening
      symptom ratings. These results suggest a direct or indirect association of
      elevated amyloid beta levels with worsening anxious-depressive symptoms and
      support the hypothesis that emerging neuropsychiatric symptoms represent an early
      manifestation of preclinical Alzheimer's disease.

PMID- 29325448
TI  - Impact of CYP2C19 Genotype on Escitalopram Exposure and Therapeutic Failure: A
      Retrospective Study Based on 2,087 Patients.
AB  - OBJECTIVE: The antidepressant escitalopram is predominantly metabolized by the
      polymorphic CYP2C19 enzyme. The authors investigated the effect of CYP2C19
      genotype on exposure and therapeutic failure of escitalopram in a large patient
      population. METHOD: A total of 4,228 escitalopram serum concentration
      measurements from 2,087 CYP2C19-genotyped patients 10-30 hours after drug intake
      were collected retrospectively from the drug monitoring database at Diakonhjemmet
      Hospital in Oslo. The patients were divided into subgroups based on CYP2C19
      genotype: those carrying inactive (CYP2C19Null) and gain-of-function (CYP2C19*17)
      variant alleles. The between-subgroup differences in escitalopram exposure
      (endpoint: dose-harmonized serum concentration) and therapeutic failure
      (endpoint: switching to another antidepressant within 1 year after the last
      escitalopram measurement) were evaluated by multivariate mixed model and chi
      square analysis, respectively. RESULTS: Compared with the CYP2C19*1/*1 group,
      escitalopram serum concentrations were significantly increased 3.3-fold in the
      CYP2C19Null/Null group, 1.6-fold in the CYP2C19*Null/*1 group, and 1.4-fold in
      the CYP2C19Null/*17 group, whereas escitalopram serum concentrations were
      significantly decreased by 10% in the CYP2C19*1/*17 group and 20% in the
      CYP1C19*17/*17 group. In comparison to the CYP2C19*1/*1 group, switches from
      escitalopram to another antidepressant within 1 year were 3.3, 1.6, and 3.0 times
      more frequent among the CYP2C19Null/Null, CYP2C19*1/*17, and CYP1C19*17/*17
      groups, respectively. CONCLUSIONS: The CYP2C19 genotype had a substantial impact
      on exposure and therapeutic failure of escitalopram, as measured by switching of
      antidepressant therapy. The results support the potential clinical utility of
      CYP2C19 genotyping for individualization of escitalopram therapy.

PMID- 29325450
TI  - Symptom Science: Omics Supports Common Biological Underpinnings Across Symptoms.
AB  - For precision health care to be successful, an in-depth understanding of the
      biological mechanisms for symptom development and severity is essential. Omics
      based research approaches facilitate identification of the biological
      underpinnings of symptoms. We reviewed literature for omics-based approaches and
      exemplar symptoms (sleep disruption, cognitive impairment, fatigue,
      gastrointestinal [GI] distress, and pain) to identify genes associated with the
      symptom or symptoms across disease processes. The review yielded 27 genes
      associated with more than one symptom. ABCB1 (MDR1), APOE, BDNF, CNR1, COMT, DAT1
      (SLC6A3), DRD4, ESR1, HLA-DRB1, IL10, IL1B, IL6, LTA, PTGS2 (COX-2), SLC6A4, and
      TNF were associated with cognitive impairment and pain, which had the most genes
      in common. COMT and TNF were related to all symptoms except sleep disruption.
      IL1B was associated with all symptoms except cognitive impairment. IL10, IL1A,
      IL1B, IL1RN, IL6, and IL8 (CXCL8) were linked with all the exemplar symptoms in
      various combinations. ABCB1 (MDR1) and SLC6A4 were associated with cognitive
      impairment, GI distress, and pain. IL10 and IL6 were linked to cognitive
      impairment, fatigue, and pain. APOE and BDNF were associated with sleep
      disruption, cognitive impairment, and pain. The 27 genes were associated with
      canonical pathways including immune, inflammatory, and cell signaling. The
      pathway analysis generated a 15-gene model from the 27 as well as 3 networks,
      which incorporated new candidate genes. The findings support the hypothesis of
      overlapping biological underpinnings across the exemplar symptoms. Candidate
      genes may be targeted in future omics research to identify mechanisms of co
      occurring symptoms for potential precision treatments.

PMID- 29325449
TI  - Analysis of DNA Methylation in Young People: Limited Evidence for an Association
      Between Victimization Stress and Epigenetic Variation in Blood.
AB  - OBJECTIVE: DNA methylation has been proposed as an epigenetic mechanism by which
      early-life experiences become "embedded" in the genome and alter transcriptional
      processes to compromise health. The authors sought to investigate whether early
      life victimization stress is associated with genome-wide DNA methylation. METHOD:
      The authors tested the hypothesis that victimization is associated with DNA
      methylation in the Environmental Risk (E-Risk) Longitudinal Study, a nationally
      representative 1994-1995 birth cohort of 2,232 twins born in England and Wales
      and assessed at ages 5, 7, 10, 12, and 18 years. Multiple forms of victimization
      were ascertained in childhood and adolescence (including physical, sexual, and
      emotional abuse; neglect; exposure to intimate-partner violence; bullying; cyber
      victimization; and crime). RESULTS: Epigenome-wide analyses of polyvictimization
      across childhood and adolescence revealed few significant associations with DNA
      methylation in peripheral blood at age 18, but these analyses were confounded by
      tobacco smoking and/or did not survive co-twin control tests. Secondary analyses
      of specific forms of victimization revealed sparse associations with DNA
      methylation that did not replicate across different operationalizations of the
      same putative victimization experience. Hypothesis-driven analyses of six
      candidate genes in the stress response (NR3C1, FKBP5, BDNF, AVP, CRHR1, SLC6A4)
      did not reveal predicted associations with DNA methylation in probes annotated to
      these genes. CONCLUSIONS: Findings from this epidemiological analysis of the
      epigenetic effects of early-life stress do not support the hypothesis of robust
      changes in DNA methylation in victimized young people. We need to come to terms
      with the possibility that epigenetic epidemiology is not yet well matched to
      experimental, nonhuman models in uncovering the biological embedding of stress.

PMID- 29325451
TI  - Expression of Sestrin Genes in Radiotherapy for Prostate Cancer and Its
      Association With Fatigue: A Proof-of-Concept Study.
AB  - : Genetic factors that influence inflammation and energy production/expenditure
      in cells may affect patient outcomes following treatment with external beam
      radiation therapy (EBRT). Sestrins, stress-inducible genes with antioxidant
      properties, have recently been implicated in several behaviors including fatigue.
      This proof-of-concept study explored whether the sestrin family of genes ( SESN1,
      SESN2, and SESN3) were differentially expressed from baseline to the midpoint of
      EBRT in a sample of 26 Puerto Rican men with nonmetastatic prostate cancer. We
      also examined whether changes in expression of these genes were associated with
      changes in fatigue scores during EBRT. METHOD: Participants completed the 13-item
      Functional Assessment of Cancer Therapy-Fatigue subscale, Spanish version. Whole
      blood samples were collected at baseline and at the midpoint of EBRT. Gene
      expression data were analyzed using the limma package in the R (version R
      2.14.0.) statistical software. Linear models and empirical Bayes moderation,
      adjusted for radiation fraction (total number of days of prescribed radiation
      treatment), were used to examine potential associations between changes in gene
      expression and change in fatigue scores. RESULTS: Expression of SESN3 (adjusted p
      < .01, log fold change -0.649) was significantly downregulated during EBRT,
      whereas the expressions of SESN1 and SESN2 remained unchanged. After adjustment
      for radiation fraction, change in SESN3 expression was associated with change in
      fatigue during EBRT (false discovery rate <.01). CONCLUSIONS: Downregulation of
      SESN3, a novel pharmacoactive stress response gene, was associated with fatigue
      intensification during EBRT. SESN3 may serve as an interventional target and a
      biomarker for the cellular and molecular events associated with EBRT-related
      fatigue.

PMID- 29325453
TI  - Age-related lung tissue remodeling due to the local distribution of MMP-2, TIMP
      2, TGF-beta and Hsp70.
AB  - Lung tissue remodeling requires complex interactions of matrix metalloproteinases
      (MMPs), tissue inhibitors of metalloproteinases (TIMPs), transforming growth
      factor (TGF) family and heat shock protein 70 (Hsp70). We evaluated the
      appearance and distribution of MMP-2, TIMP-2, TGF-beta1 and Hsp70 in lung tissue
      using immunohistochemistry. Stained structures were graded semiquantitatively.
      Overall, more MMP-2, TIMP-2, TGF-beta1 and Hsp70 were observed in bronchial
      cartilage, bronchial and alveola repithelium, and among alveolar macrophages. We
      evaluated mostly alveolar macrophages, bronchial epithelial cells and mucosal
      fibroblasts stained for TGF-beta1, MMP-2 and TIMP-2. We also assessed strong or
      moderate correlations between numbers of cells containing TGF-beta1, MMP-2, TIMP
      2 in patients >= 60 years old. The presence of less TGF-beta1 and more MMP-2,
      TIMP-2 and Hsp70 containing cells in all tissue groups indicated that local
      regulation was more dependent on MMP-2, TIMP-2 and Hsp70 distribution. Fewer TIMP
      2, Hsp70 and TGF-beta1 immunoreactive cells in younger individuals and increased
      expression of Hsp70 in elderly individuals demonstrated the influence of aging in
      lung remodeling. Findings of MMP-2, TIMP-2 and TGF-beta1 immunoreactive cells in
      elderly individuals indicate lung remodeling due to aging.

PMID- 29325444
TI  - Redox Paradox: A Novel Approach to Therapeutics-Resistant Cancer.
AB  - SIGNIFICANCE: Cancer cells that are resistant to radiation and chemotherapy are a
      major problem limiting the success of cancer therapy. Aggressive cancer cells
      depend on elevated intracellular levels of reactive oxygen species (ROS) to
      proliferate, self-renew, and metastasize. As a result, these aggressive cancers
      maintain high basal levels of ROS compared with normal cells. The prominence of
      the redox state in cancer cells led us to consider whether increasing the redox
      state to the condition of oxidative stress could be used as a successful adjuvant
      therapy for aggressive cancers. Recent Advances: Past attempts using antioxidant
      compounds to inhibit ROS levels in cancers as redox-based therapy have met with
      very limited success. However, recent clinical trials using pro-oxidant compounds
      reveal noteworthy results, which could have a significant impact on the
      development of strategies for redox-based therapies. CRITICAL ISSUES: The major
      objective of this review is to discuss the role of the redox state in aggressive
      cancers and how to utilize the shift in redox state to improve cancer therapy. We
      also discuss the paradox of redox state parameters; that is, hydrogen peroxide
      (H2O2) as the driver molecule for cancer progression as well as a target for
      cancer treatment. FUTURE DIRECTIONS: Based on the biological significance of the
      redox state, we postulate that this system could potentially be used to create a
      new avenue for targeted therapy, including the potential to incorporate
      personalized redox therapy for cancer treatment.

PMID- 29325452
TI  - Inherited Cancer in the Age of Next-Generation Sequencing.
AB  - Next-generation sequencing (NGS) technology has led to the ability to test for
      multiple cancer susceptibility genes simultaneously without significantly
      increasing cost or turnaround time. With growing usage of multigene testing for
      inherited cancer, ongoing education for nurses and other health-care providers
      about hereditary cancer screening is imperative to ensure appropriate testing
      candidate identification, test selection, and posttest management. The purpose of
      this review article is to (1) provide an overview of how NGS works to detect
      germline mutations, (2) summarize the benefits and limitations of multigene panel
      testing, (3) describe risk categories of cancer susceptibility genes, and (4)
      highlight the counseling considerations for patients pursuing multigene testing.

PMID- 29325454
TI  - Down-expression of P2RX2, KCNQ5, ERBB3 and SOCS3 through DNA hypermethylation in
      elderly women with presbycusis.
AB  - CONTEXT: Presbycusis, an age-related hearing impairment (ARHI), represents the
      most common sensory disability in adults. Today, the molecular mechanisms
      underlying presbycusis remain unclear. This is in particular due to the fact that
      ARHI is a multifactorial complex disorder resulting from several genomic factors
      interacting with lifelong cumulative effects of: disease, diet, and environment.
      OBJECTIVE: Identification of novel biomarkers for presbycusis. MATERIALS AND
      METHODS: We selectively ascertained 18 elderly unrelated women lacking
      environmental and metabolic risk factors. Subsequently, we screened for
      methylation map changes in blood samples of women with presbycusis as compared to
      controls, using reduced representation bisulfite sequencing. We focused on
      hypermethylated cytosine bases located in gene promoters and the first two exons.
      To elucidate the related gene expression changes, we performed transcriptomic
      study using gene expression microarray. RESULTS: Twenty-seven genes, known to be
      expressed in adult human cochlea, were found in the blood cells to be
      differentially hypermethylated with significant (p < 0.01) methylation
      differences (>30%) and down-expressed with fold change >1.2 (FDR <0.05).
      Functional annotation and qRT-PCR further identified P2RX2, KCNQ5, ERBB3 and
      SOCS3 to be associated with the progression of ARHI. DISCUSSION AND CONCLUSION:
      Down-expressed genes associated with DNA hypermethylation could be used as
      biomarkers for understanding complex pathogenic mechanisms underlying
      presbycusis.

PMID- 29325455
TI  - Influence of middle-distance running on muscular micro RNAs.
AB  - A specific subset of micro RNAs (miRs), including miR-133 and miR-206, is
      specifically expressed in muscle tissue, so that they are currently defined as
      muscular miRs (myomiRs). To further elucidate the role of myomiRs in muscle
      biology, we measured miR-133a and miR-206 in plasma of 28 middle-age recreational
      athletes. The study population consisted of 28 middle aged, recreation athletes
      (11 women and 17 men; mean age, 46 years) who completed a 21.1 km, half-marathon.
      The plasma concentration of miR-133a and miR-206, the serum concentration of
      creatine kinase (CK) and high-sensitivity (HS) cardiac troponin T (cTnT), as well
      as capillary lactate, were measured before and immediately after the run. The
      median serum concentration of total CK (257 versus 175 U/L; p < .001), cTnT (17.8
      versus 5.6 ng/L; p < .001), and the plasma values of both miR-133a (4.22 versus
      0.64 * 10-4; p < .001) and miR-206 (1.36 versus 0.63 * 10-4; p = .001) were
      considerably increased immediately after the half-marathon run. In multivariate
      analysis only post-exercise capillary lactate was found to be independently
      associated with running time. A significant and independent correlation was
      observed between plasma variations of the two miRs, but not with other
      physiological or laboratory parameters. The results of this study suggest that
      the biological significance of miR-133a and 206 variation after middle-distance
      running parallels but not overlaps the release of biomarkers of nonspecific
      tissue damage. Enhanced plasma values of these myomiRs may hence reflect a
      physiological response to high-intensity and/or prolonged exercise rather than
      tissue injury.

PMID- 29325456
TI  - Dual-purpose vardenafil hydrochloride/dapoxetine hydrochloride orodispersible
      tablets: in vitro formulation/evaluation, stability study and in vivo comparative
      pharmacokinetic study in healthy human subjects.
AB  - Erectile dysfunction (ED) is the most important disorder after premature
      ejaculation for sexual activity in men. Vardenafil hydrochloride (VH) is an oral
      therapy for the treatment of erectile dysfunction. VH oral disintegrating tablets
      (ODTs) have been prepared by freeze drying technique to improve its dissolution
      profile and the overall clinical performance. Dapoxetine hydrochloride (DH) was
      added to the best three formulae of the prepared VH ODTs to treat premature
      ejaculation. All the ODTs formulae were evaluated for weight variation,
      friability, drug content, in vitro disintegration time, wetting time, and the
      dissolution study. Gelatin as a matrix former with N-methylpyrrolidone as a
      solubilizer in VH/DH ODTs improved the dissolution rate and extent of release of
      VH and DH with 100% of drug being dissolved after 15 min. In vivo study results
      from six healthy male volunteers showed shorter Tmax of VH from VH/DH ODT of
      0.583 +/- 0.129 h and shorter Tmax of DH from VH/DH ODT of 0.625 +/- 0.137 h and
      showed AUC0-12 of VH from VH/DH ODT of 39.234 +/- 10.932 ng/ml h1 and AUC0-12 of
      DH from VH/DH ODT of 531.681 +/- 129.544 ng/ml h1, with relative bioavailability
      values of 100.9 and 85%, respectively, compared to (Levitra(r)) and (Priligy(r)).

PMID- 29325458
TI  - A diagnostic test accuracy meta-analysis of maternal serum ischemia-modified
      albumin for detection of preeclampsia.
AB  - BACKGROUND/AIMS: Ischemia-modified albumin (IMA) has been widely accepted as a
      serological biomarker. IMA has been proposed as a simple and novel marker of
      oxidative stress in preeclampsia (PE). This systematic review and diagnostic test
      accuracy meta-analysis aims to evaluate the diagnostic accuracy of this novel
      serological biomarker, IMA to detect PE. METHODS: A systematic search of major
      databases was performed to identify all published diagnostic accuracy studies on
      IMA. Risk of bias and applicability concerns were assessed for included studies.
      Summary estimates; the pooled sensitivity, specificity, and the diagnostic odds
      ratio (DOR) of IMA for the diagnosis of PE were computed using random-effects
      models. The overall test performance was summarized using summary receiver
      operating characteristic (SROC) curve analysis. RESULTS: Six articles were
      included in this meta-analysis. The overall estimates of IMA in detecting PE were
      pooled sensitivity; 0.80 (95%CI 0.73-0.86), pooled specificity; 0.76 (95%CI 0.70
      0.81), DOR; 14.32 (95%CI 5.06-40.57), and area under curve (AUC); 0.860. There
      was no between-study heterogeneity due to threshold effect. CONCLUSIONS: This
      meta-analysis showed IMA could be useful as a biomarker for PE with good accuracy
      (AUC = 0.860). However, further research is needed for re-evaluation and clinical
      validation of fairly promising results of this meta-analysis.

PMID- 29325459
TI  - Is cord blood hepcidin influenced by the low-grade acute-phase response occurring
      during delivery? A small-scale longitudinal study.
AB  - AIM: To measure serum hepcidin in late pregnancy and in cord blood, and to
      analyze relationship between hepcidin, interleukin-6, and biomarkers of fetal
      iron status. MATERIALS AND METHODS: Data from 15 uncomplicated singleton
      pregnancies were analyzed longitudinally in trimester 3 (T3) and at birth.
      RESULTS: In T3, S-ferritin (median 14 ug/L) and transferrin (median 4.0 g/L)
      indicated low iron status, whereas the median soluble transferrin receptor (sTfR)
      was 4.0 mg/L, i.e. within the reference interval. Median T3 S-hepcidin was 7.8
      ng/mL. Later on in cord blood, ferritin concentration (180 ug/L) were
      significantly higher, transferrin concentration (1.8 g/L) were significantly
      lower, and both sTfR (4.7 mg/L) and S-hepcidin concentrations (30.5 ng/mL) were
      significantly higher than maternal T3 concentrations. At the same time, cord
      blood interleukin-6 indicated an activated acute-phase reaction. In T3, after
      logarithmic transformation, there was a significant correlation between S
      hepcidin and both S-ferritin (r = 0.691) and sTfR (r = -0.825). There was also a
      significant correlation between S-ferritin and both sTfR (r = -0.729) and
      transferrin (r = 0.549) in T3. CONCLUSIONS: Although S-ferritin, S-hepcidin, and
      sTfR were correlated during pregnancy, these relationships were not apparent in
      umbilical cord blood. Further, cord blood interleukin-6 indicated an activated
      acute-phase response, and sTfR, which is known to be unaffected by inflammation,
      indicated a low iron status in cord blood. Thus, instead of representing an
      enhanced iron status, the data appear to suggest that hepcidin and ferritin in
      cord blood may be influenced by the low-grade acute-phase response that occurs
      during delivery.

PMID- 29325457
TI  - Synthetic Adeno-Associated Viral Vector Efficiently Targets Mouse and Nonhuman
      Primate Retina In Vivo.
AB  - Gene therapy is a promising approach in the treatment of inherited and common
      complex disorders of the retina. Preclinical and clinical studies have validated
      the use of adeno-associated viral vectors (AAV) as a safe and efficient delivery
      vehicle for gene transfer. Retinal pigment epithelium and rods-and to a lesser
      extent, cone photoreceptors-can be efficiently targeted with AAV. Other retinal
      cell types however are more challenging targets. The aim of this study was to
      characterize the transduction profile and efficiency of in silico designed,
      synthetic Anc80 AAVs for retinal gene transfer. Three Anc80 variants were
      evaluated for retinal targeting in mice and primates following subretinal
      delivery. In the murine retina Anc80L65 demonstrated high level of retinal
      pigment epithelium and photoreceptor targeting with comparable cone photoreceptor
      affinity compared to other AAVs. Remarkably, Anc80L65 enhanced transduction
      kinetics with visible expression as early as day 1 and steady state mRNA levels
      at day 3. Inner retinal tropism of Anc80 variants demonstrated distinct
      transduction patterns of Muller glia, retinal ganglion cells and inner nuclear
      layer neurons. Finally, murine findings with Anc80L65 qualitatively translated to
      the Rhesus macaque in terms of cell targets, levels and onset of expression. Our
      findings support the use of Anc80L65 for therapeutic subretinal gene delivery.

PMID- 29325460
TI  - Targeted delivery of melittin to cancer cells by AS1411 anti-nucleolin aptamer.
AB  - Melittin, a small water-soluble cationic amphipathic alpha-helical linear
      peptide, consisted of 26 amino acids, is the honeybee venom major constituent.
      Several reports have proved the lytic and apoptotic effects of melittin in
      several cancerous cell lines. In this study, we aimed to fabricate an AS1411
      aptamer-melittin to specifically deliver melittin to nucleolin positive cells
      (A549). Melittin was covalently attached to antinucleolin aptamer (AS1411) and
      its toxicity in A549 (nucleolin positive) and L929 (nucleolin negative) was
      studied using MTT and Annexin V flow cytometry methods. Aptamer-melittin
      conjugate formation was confirmed by gel electrophoresis. Hemolytic effect of
      aptamer-melittin conjugate was compared to melittin alone. The aptamer-melittin
      conjugate showed efficient cell uptake and was more cytotoxic in A549 cells than
      melittin (p < .001). This complex was less toxic in control cells. Competitive
      inhibition assay confirmed that aptamer-melittin complex delivery occurred
      through receptor-ligand interaction on the cell surface. Moreover, aptamer
      melittin showed a significantly less hemolytic activity as compared with free
      melittin. This study showed that melittin could be specifically delivered to A549
      cells when it was covalently conjugated to antinucleolin aptamer (AS1411) in
      vitro. This system can reduce the cytotoxic effects of melittin on cells with no
      nucleolin receptor overexpression which comprise most of normal cells such as
      L929 cells.

PMID- 29325461
TI  - Different analgesics prior to intrauterine device insertion: is there any
      evidence of efficacy?

PMID- 29325462
TI  - Tocilizumab treatment in patients with rheumatoid arthritis is associated with
      reduced fibrinogen levels and increased blood loss after total knee arthroplasty.
AB  - OBJECTIVE: Since IL-6 has been associated with activation of the coagulation
      cascade and upregulation of fibrinogen transcription, we retrospectively tested
      the hypothesis that patients with rheumatoid arthritis (RA) treated with
      tocilizumab (TCZ) may lose more blood when undergoing total knee arthroplasty
      (TKA). METHODS: This study included 115 RA patients who underwent primary TKA and
      were preoperatively tested for fibrinogen levels. The blood volume of each
      patient was calculated using the Nadler formula, and estimated blood loss after
      TKA was calculated as the change between pre-operative and post-operative
      hematocrits. If salvaged blood was reinfused, the volume was measured and added
      to the volume of the estimated blood loss. RESULTS: We observed that patients
      treated with TCZ had significantly lower pre-operative fibrinogen levels than
      those not treated with TCZ (190.0 mg/dL versus 347.0 mg/dL, respectively; p =
      .00018). We also observed a statistically significant increase in mean total
      volume of estimated blood loss after TKA in RA patients who had been treated with
      TCZ compared with those not treated with TCZ (797.1 mL versus 511.4 mL,
      respectively; p = .0039). CONCLUSION: TCZ treatment in patients with RA may
      increase the risk of blood loss after TKA because of decreased fibrinogen levels.

PMID- 29325464
TI  - The clinical course of patients with rheumatoid arthritis who underwent
      orthopaedic surgeries under disease control by tofacitinib.

PMID- 29325463
TI  - Compared With Elastin Stains, h-Caldesmon and Desmin Offer Superior Detection of
      Vessel Invasion in Gastric, Pancreatic, and Colorectal Adenocarcinomas.
AB  - BACKGROUND: The presence of vessel invasion is considered indicative of a poor
      prognosis in many malignant tumors. We aimed to compare the sensitivity of
      elastin stains (van Gieson's and orcein methods) with 2 smooth muscle markers (h
      caldesmon and desmin) in gastric, pancreatic, and colorectal adenocarcinoma
      specimens. MATERIALS AND METHODS: We used 27 (29.3%) gastric, 35 (38.0%)
      pancreatic, and 30 (32.6%) colorectal resection specimens. We applied a
      provisional classification of vessel invasion patterns: type A, a focus with a
      nearby artery unaccompanied by a vein; type T, a focus at the invasive front
      without an unaccompanied artery; and type X, foci that only appeared by any of
      the 4 stains used. RESULTS: There were 369 foci. The smooth muscle markers were
      more sensitive than the elastin stains, and h-caldesmon more sensitive than
      desmin, in all types. Among the 139 type A foci, 33 (23.7%) were positive by
      desmin and h-caldesmon, whereas the elastin stains were not ( P = .001). h
      Caldesmon was the only positive marker in 11 (7.9%; P = .011). Among the 78 type
      T foci, 21 (26.9%) were positive by desmin and h-caldesmon, when both elastin
      stains were negative ( P = .000). In 16 (20.5%) foci, h-caldesmon was the only
      positive marker ( P = .002). Among 152 type X foci, 91 (59.9%) were positive by
      all markers, 26 (17.1%) by both desmin and h-caldesmon, and 9 (5.9%) by only the
      2 elastin stains ( P = .001). CONCLUSION: We recommend these stains for suspect
      foci in gastric, pancreatic, and colorectal adenocarcinoma specimens. They might
      highlight both predictable and unpredictable foci.

PMID- 29325466
TI  - The correlation between birth weight and insulin-like growth factor-binding
      protein-1 (IGFBP-1), kisspeptin-1 (KISS-1), and three-dimensional fetal volume.
AB  - PURPOSE: This study aimed to determine the relationship between birth weight, and
      maternal serum insulin-like growth factor-binding protein-1 (IGFBP-1) and
      kisspeptin-1 (KISS-1) levels, and first-trimester fetal volume (FV) based on
      three-dimensional ultrasonography. MATERIALS AND METHODS: The study included 142
      pregnant women at gestational week 11 degrees -136. All fetuses were imaged
      ultrasonographically by the same physician. Maternal blood samples were collected
      at the time of ultrasonographic evaluation and analyzed for IGFBP-1 and KISS-1
      levels via enzyme-linked immunosorbent assay (ELISA). Maternal and neonatal
      weights were recorded at birth. Birth weight <=10th and the >90th percentiles was
      defined as small and large for gestational age (SGA and LGA), respectively.
      RESULTS: Median crown-rump length (CRL), FV, and maternal serum IGFBP-1 and KISS
      1 levels were 58.2 mm (35.3-79.2 mm), 16.3 cm3 (3.8-34.4 cm3), 68.1 ng mL-1 (3.8
      377.9 mL-1), and 99.7 ng L-1 (42.1-965.3 ng L-1), respectively. First-trimester
      IGFBP-1 levels were significantly lower in the mothers with LGA neonates (p <
      .05). There was a significant positive correlation between CRL and FV, and
      between the IGFBP-1 and KISS-1 levels. IGFBP-1 levels and maternal weight at
      delivery were negatively correlated with neonatal birth weight. There was no
      correlation between CRL or FV and maternal IGFBP-1 or KISS1 levels (p > .05). The
      maternal IGFBP-1 level during the first trimester was a significant independent
      factor for SGA and LGA neonates (Odds ratio (OR): 0.011, 95%CI: 1.005-1.018, p <
      .001; and OR: 1.297, 95%CI: 1.074-1.566, p = .007, respectively). There was no
      significant relationship between SGA or LGA, and CRL, FV, or the KISS-1 level.
      CONCLUSIONS: As compared to the maternal KISS-1 level, the maternal IGFBP-1 level
      during the first trimester might be a better biomarker of fetal growth.
      Additional larger scale studies are needed to further delineate the utility of
      IGFBP-1 as a marker of abnormal birth weight.

PMID- 29325465
TI  - Prevalence of positive QuantiFERON gold in-tube testing in hidradenitis
      suppurativa.
AB  - AIM: Hidradenitis suppurativa (HS) is a chronic, recurrent, inflammatory disease
      of the apocrine sweat glands. Tumor necrosis factor-alpha (TNF-alpha) inhibitors
      are commonly used to treat HS. However, prior to initiating therapy patients must
      be screened for mycobacterium tuberculosis (mTB) exposure. Several mTB screening
      tests based on interferon gamma release assays are commercially available, but
      the performance of these assays in the HS population is unknown. The purpose of
      this study was to investigate the performance of the QuantiFERON gold in-tube
      assay (QFT-GIT) in a cohort of patients with HS. METHODS: This prospective study
      was conducted through the Wound Etiology and Healing (WE-HEAL) study. QFTGIT
      testing was performed using a commercial laboratory. Patients with positive test
      results underwent follow-up testing to evaluate for latent tuberculosis infection
      (LTBI). Data were collected on demographics and disease activity scores including
      Hurley stage, HS Sartorius score (HSS) and active nodule (AN) count. RESULTS: Of
      the 69 patients with a confirmed diagnosis of HS, seven (10.1%) tested QFT-GIT
      positive and 5.8% were diagnosed with LTBI. CONCLUSIONS: QFT-GIT results did not
      correlate with demographic characteristics or HS disease activity.

PMID- 29325467
TI  - Natasha Caruana: Timely Tale.

PMID- 29325468
TI  - Does "Enhanced Support" for Offenders Effectively Reduce Custodial Violence and
      Disruption? An Evaluation of the Enhanced Support Service Pilot.
AB  - This study aimed to examine the effectiveness of The Enhanced Support Service
      (ESS) pilot in reducing custodial violence and disruption, and the associated
      costs, by observing the behavioural change of the 35 service users who
      participated in ESS intervention within its first 22 months of operation.
      Frequencies of recorded incidents of aggressive behaviours, self-harming
      behaviours, noncompliance, and positive behaviours were counted from routine
      administrative systems using a coding structure developed in previous studies.
      The count data were analysed using nonparametric tests and Poisson regression
      models to derive an Incident Rate Ratio (IRR). Findings suggest the ESS is
      associated with a reduction in aggressive behaviours and noncompliance, with
      medium to large effect sizes ( r = .31-.53); however, it was not associated with
      a reduction in deliberate self-harm or increased positive behaviours. The Poisson
      models revealed that levels of pre-intervention behaviour, intervention length,
      intervention completion, and service location had varying effects on
      postintervention behaviour, with those who completed intervention demonstrating
      more favourable outcomes. The ESS service model was associated with a reduction
      in behaviour that challenges, which has implications for the reduction in
      associated social, economic, and political costs-as well as the commissioning of
      interventions and future research in this area.

PMID- 29325469
TI  - Current update of a thermosensitive liposomes composed of DPPC and Brij78.
AB  - Thermosensitive liposomes (TSLs) have been a prominent area of study in the
      discipline of tumour-targeted chemotherapeutics. The representative product of
      TSLs is ThermoDox(r) (DPPC/lyso-PC/PEG-lipid), which has advanced to Phase III
      clinical trials. Various groups have sought to develop a new TSL to improve upon
      the LTSL (lyso-lipid temperature-sensitive liposomes) formulation that is used to
      prepare ThermoDOX(r). This review focuses on the development and recent update of
      an innovative TSL formulation, HaT-liposomes composed of DPPC and Brij78. Various
      parameters of LTSL and HaT-liposomes are compared, including size, loading
      efficiency, transition temperature, temperature-dependent release kinetics,
      stability, pharmacokinetics, biodistribution and antitumour activity. Theranostic
      techniques involving HaT-liposomes are reported with regard to magnetic resonance
      imaging of drug delivery to tumours and identification of an early therapeutic
      biomarker in the treated tumour. The development of a further improved TSL
      formulation upon HaT-liposomes with improved stability and prolonged blood
      circulation is reported. Delivery of membrane impermeable drugs using HaT
      liposomes is explored. Finally, the challenges and future perspectives of this
      technology are discussed.

PMID- 29325470
TI  - The effect of shorter exposure versus prolonged exposure on treatment outcome in
      Tourette syndrome and chronic tic disorders - an open trial.
AB  - BACKGROUND: Exposure and response prevention has shown to be an effective
      strategy and is considered a first-line intervention in the behavioural treatment
      of tic disorders. Prior research demonstrated significant tic reduction after 12
      two hour sessions. OBJECTIVE: In this open trial, the question is addressed
      whether, relative to these prolonged sessions, exposure sessions of shorter
      duration yield differential outcome for patients with tic disorders. METHODS: A
      total of 29 patients diagnosed with Tourette syndrome (TS) or chronic tic
      disorder were treated with shorter exposure sessions (1 h), and these data were
      compared to the data from a study about prolonged exposure (2 h, n = 21). Outcome
      was measured by the Yale Global Tic Severity Scale (YGTSS). RESULTS: Results
      suggest that after taking the difference in illness duration between the two
      groups into account, the effectiveness of shorter exposure sessions is not
      inferior to that of prolonged exposure. CONCLUSIONS: Results suggest that
      treatment with shorter exposure might be more efficient and more patients can be
      reached. Future research is needed to gain more insight into the mechanisms
      underlying the efficacy of behavioural treatments for tics.

PMID- 29325471
TI  - Intracranial subarachnoid hemorrhage following cervical laminoplasty: a report of
      two cases.
AB  - Intracranial hemorrhage is a rare complication of spinal surgery. Case 1 was a 58
      year-old man who underwent cervical laminoplasty. No apparent iatrogenic dural
      rupture or cerebrospinal fluid leakage was observed. An hour after the surgery,
      the patient had convulsions and became restless thereafter. CT revealed an
      intracranial subarachnoid hemorrhage (SAH). The patient recovered normal
      consciousness the next morning. Case 2 was a 68-year-old woman who underwent
      cervical laminoplasty without postoperative cerebrospinal fluid leakage. Six days
      after the surgery, the patient continued to complain of nausea and headache. By
      13 days, the patient reported relief from her symptoms. There was no evidence of
      cerebral aneurysm, or vascular malformation in both cases. Patients undergoing
      cervical laminoplasty might be at risk for developing SAH. Careful attention to
      intraoperative neck positioning, strict monitoring and control of perioperative
      blood pressure, and complete dural repair are essential measures for preventing
      SAH.

PMID- 29325472
TI  - Latent psychological distress existing behind a set of assessment measures is
      comparable to or more important than symptoms or disability in the association
      with quality of life and working status of patients with rheumatoid arthritis.
AB  - OBJECTIVES: To identify the determinant of patients' perspectives of quality of
      life (QOL) and working status out of analysis-derived components underlying a set
      of assessment measures of the status of patients with rheumatoid arthritis (RA).
      METHODS: From the NinJa database in Japan (2012-2014), 1455 RA patients with
      DAS28 > 3.2 were recruited. Components explaining RA status were derived from
      principal component analysis of 15 assessment measures. Multivariate regression
      was used to examine the relative contribution of each identified component to the
      EuroQOL-5 Dimension Questionnaire score and working status. RESULTS: Among the
      identified components (patient symptoms, physical disability, evaluated symptoms,
      patient distress, inflammatory marker, and serological marker), patient distress
      showed highest contribution to EuroQOL for both male (44.6%) and female patients
      (39.3%). Physical disability was associated with significantly less participation
      in paid work in male (odds ratio [OR]; 0.63) and both household and paid work in
      female (OR; 0.82 and 0.54, respectively), though patient distress showed the
      strongest association with less participation in both household and paid work in
      female (OR; 0.64 and 0.45, respectively). CONCLUSION: The approach to latent
      patient distress using psychological screening tools, concurrently with the
      treatment to control the activity of arthritis, can be help to improve health
      related QOL (HRQOL) including work participation.

PMID- 29325473
TI  - Photographic sequence- drainage process of a myxoid cyst.

PMID- 29325474
TI  - Visual representation of medical information: the importance of considering the
      end-user in the design of medical illustrations.
AB  - This practice led research project explored visual representation through
      illustrations designed to communicate often complex medical information for
      different users within Auckland City Hospital, New Zealand. Media and tools were
      manipulated to affect varying degrees of naturalism or abstraction from reality
      in the creation of illustrations for a variety of real-life clinical projects,
      and user feedback on illustration preference gathered from both medical
      professionals and patients. While all users preferred the most realistic
      representations of medical information from the illustrations presented, patients
      often favoured illustrations that depicted a greater amount of information than
      professionals suggested was necessary.

PMID- 29325475
TI  - Investigation of the mechanisms of Genkwa Flos hepatotoxicity by a cell
      metabolomics strategy combined with serum pharmacology in HL-7702 liver cells.
AB  - 1. To investigate Genkwa Flos hepatotoxicity, a cell metabolomics strategy
      combined with serum pharmacology was performed on human HL-7702 liver cells in
      this study. 2. Firstly, cell viability and biochemical indicators were determined
      and the cell morphology was observed to confirm the cell injury and develop a
      cell hepatotoxicity model. Then, with the help of cell metabolomics based on UPLC
      MS, the Genkwa Flos group samples were completely separated from the blank group
      samples in the score plots and seven upregulated as well as two down-regulated
      putative biomarkers in the loading plot were identified and confirmed. Besides,
      two signal molecules and four enzymes involved in biosynthesis pathway of
      lysophosphatidylcholine and the sphingosine kinase/sphingosine-1-phosphate
      pathway were determined to investigate the relationship between Genkwa Flos
      hepatotoxicity and these two classic pathways. Finally, the metabolic pathways
      related to specific biomarkers and two classic metabolic pathways were analyzed
      to explain the possible mechanism of Genkwa Flos hepatotoxicity. 3. Based on the
      results, lipid peroxidation and oxidative stress, phospholipase
      A2/lysophosphatidylcholine pathway, the disturbance of sphingosine-1-phosphate
      metabolic profile centered on sphingosine kinase/sphingosine-1-phosphate pathway
      and fatty acid metabolism might be critical participators in the progression of
      liver injury induced by Genkwa Flos.

PMID- 29325476
TI  - Twelve weeks of ombitasvir/paritaprevir/r and dasabuvir without ribavirin is
      effective and safe in the treatment of patients with HCV genotype 1b infection
      and compensated cirrhosis: results from a real-world cohort study.
AB  - OBJECTIVE: To explore the effectiveness and safety of
      ombitasvir/paritaprevir/ritonavir and dasabuvir (OBV/PTV/r+DSV) for 12 weeks
      without ribavirin in adults with chronic HCV genotype 1b infection and
      compensated cirrhosis. METHODS: Observational study of a prospective cohort of
      adult patients with HCV genotype 1b infection and compensated cirrhosis who
      received 12 weeks of OBV/PTV/r and DSV without ribavirin. Effectiveness was
      assessed by recording the percentage of patients achieving sustained virological
      response at week 12 post-treatment (SVR12). Safety outcomes were based on the
      incidence of adverse events. RESULTS: Seventy-eight patients were included. The
      SVR12 rate was 96.1% (95%CI 89.2-99.2). Adverse events were recorded in 78.0% of
      patients. Of these, 97.7% were grade 1/2. One patient discontinued treatment
      prematurely owing to adverse events. Eighty-six interactions were detected in 43
      patients (55.1%). Overall, 81.4% of interactions required close monitoring,
      alteration of drug dosage, or timing of administration. In 7.0% of cases, the
      interactions arose from contraindications that required the suspension of the
      concomitant drug. In 11.6% of cases, medicinal plants or foods were withdrawn.
      CONCLUSIONS: The simplified regimen of OBV/PTV/r+DSV administered for 12 weeks is
      effective and safe in patients with chronic HCV genotype 1b infection and
      compensated cirrhosis. No adverse reactions related to drug-drug interactions
      were recorded.

PMID- 29325477
TI  - Cognitive Performance and Apathy Predict Unemployment in Huntington's Disease
      Mutation Carriers.
AB  - Unemployment is common for those with Huntington's disease (HD), a genetic
      neurodegenerative disorder, and affects patients' quality of life. HD is
      characterized by motor disturbances, cognitive dysfunction, and psychiatric
      symptoms. The purpose of this article was to determine which clinical signs of HD
      are predictive of unemployment. Data for employed (N=114) and unemployed (N=106)
      HD mutation carriers were used to investigate group differences. Univariate
      logistic regression analyses, adjusted for age and gender, were performed to
      determine individual predictors of unemployment. Subsequently, a multivariate
      logistic regression analysis was performed, entering all significant results from
      the univariate analyses into one fully adjusted model to determine the strongest
      predictors. HD mutation carriers with lower cognitive performances and higher
      apathy scores were more likely to be unemployed than were HD mutation carriers
      with higher cognitive scores and no signs of apathy. Motor functioning was an
      independent predictor of unemployment but was not associated with unemployment in
      the fully adjusted model. Cognitive impairments, especially in the executive
      domain, and apathy were independent determinants of unemployment in HD mutation
      carriers. Motor disturbances, the clinical hallmark of HD, did not appear to be
      the most important predictor for work cessation. These results should be taken
      into consideration in clinical practice when evaluating HD patients' ability to
      work.

PMID- 29325478
TI  - Catatonia Under-Diagnosis in the General Hospital.
AB  - Catatonia is under-diagnosed in psychiatric settings. No studies have explored
      the under-diagnosis of catatonia in general hospitals. The authors conducted a
      retrospective chart review using DSM-5 criteria to diagnose catatonia in medical
      inpatients between 2011 and 2013. Of 133 case subjects meeting DSM-5 criteria for
      catatonia retrospectively, 79 had never been diagnosed and 54 had a documented
      diagnosis. Multiple logistic regression revealed that psychiatry consultation
      significantly decreased the odds of under-diagnosis of catatonia, whereas
      presence of agitation, grimacing, or echolalia increased the likelihood of under
      diagnosis. Under-diagnosed case subjects received significantly lower doses of
      lorazepam, and increased mortality during admission and increased length of
      hospital stay both fell short of statistical significance in this group.
      Catatonia appears to be frequently under-diagnosed in the general hospital, and
      psychiatry consultation services play a crucial role in its detection and
      treatment. Strategies to improve recognition and treatment of catatonia should be
      implemented.

PMID- 29325479
TI  - High Norwegian prostate cancer mortality: evidence of over-reporting.
AB  - OBJECTIVE: This study aimed to determine the level of misattribution of prostate
      cancer deaths in Norway based on the county of Vestfold in the years 2009-2014.
      MATERIALS AND METHODS: The study included 328 patients registered as dead from
      prostate cancer (PCD; part I of death certificate), 126 patients with prostate
      cancer as other significant condition at death (OCD; part II of death
      certificate) and 310 patients who died with a diagnosis of prostate cancer not
      registered on the death certificate (PC-DCneg) in Vestfold County in 2009-2014.
      The complete cohort with patients' names and dates of birth was provided by the
      Norwegian Institute of Public Health and the Norwegian Cancer Registry. The true
      cause of death of all patients was evaluated based on patient journals. RESULTS:
      Over-reporting of prostate cancer deaths in the PCD group was 33% while under
      reporting in the OCD and PC-DCneg groups was 19% and 5%, respectively. The
      correlation between registered and observed causes of death was 0.81 (95%
      confidence interval 0.78-0.83). Misattribution of prostate cancer deaths
      increased significantly with patient age and decreasing Gleason score.
      CONCLUSIONS: Prostate cancer mortality statistics in Norway are relatively
      accurate for patients aged <75 years at death. However, overall accuracy of cause
      of death assignment is significantly reduced by misattribution among older
      patients (> 75 years), who represent the large majority of prostate cancer
      deaths. Over-reporting of prostate cancer deaths among elderly people may not be
      an exclusively Norwegian phenomenon and may affect prostate cancer mortality
      statistics in other countries.

PMID- 29325480
TI  - Overweight and Obesity Among Chinese College Students: An Exploration of Gender
      as Related to External Environmental Influences.
AB  - While many studies have examined factors associated with overweight and obesity
      among college students, no study has yet compared gender differences influencing
      overweight and obesity using a multilevel framework. The present study examines
      different influences on overweight and obesity between men and women at both
      individual and environmental levels. Participants were 11,673 college students
      identified through a multistage survey sampling process conducted in 50 Chinese
      universities. The prevalence of overweight and obesity was 9.5% (95% CI [7.7,
      11.3]) in the overall study sample, 13.9% (95% CI [11.5, 16.7]) in males and 6.1%
      (95% CI [4.1, 8.1]) in females, respectively. We found that higher family income,
      perceived life stress, home region GDP, and university city unemployment were
      associated with higher overweight and obesity levels in males, independent of
      other individual- and city-level covariates. However, unlike male students, only
      unemployment was associated with overweight and obesity among females. Our
      research indicates Chinese males are more susceptible to overweight and obesity,
      and are more easily influenced by external variants than Chinese females. This
      information should be considered in formulating gender-specific policies and
      designing and implementing effective interventions to reduce the prevalence of
      overweight and obesity among young adult male college students.

PMID- 29325481
TI  - Stress management and the role of Rhodiola rosea: a review.
AB  - OBJECTIVE: Stress describes the physiological reaction to threat or pressure,
      which manifests as physical symptoms of exhaustion or energy loss and
      psychological symptoms, including irritability or tension. If untreated, chronic
      stress or burnout may develop, both are areas of unmet medical need. Evidence
      based treatment and prevention measures are needed. METHODS: Prevention
      strategies and existing treatment options for stress-related symptoms were
      evaluated to establish criteria for an adequate pharmacological approach to
      stress. The authors reviewed the literature to reach a clinically meaningful
      strategy for prevention and treatment of persistent stress symptoms and their
      consequences, including burnout and secondary diseases. RESULTS: Current
      medication reveals a treatment gap. Most drugs target only psychological or
      physical stress symptoms. Furthermore, psychotropic medications sometimes
      prescribed for stress often have unacceptable side effects and bear a risk of
      overtreatment. Ideally pharmacological therapy should afford comprehensive
      treatment of all stress symptoms with a favourable safety profile. CONCLUSIONS:
      Rhodiola rosea extract (RRE) fulfils important requirements. It is the main
      adaptogen approved by the HMPC/EMA for the indication 'stress' and influences the
      release of stress hormones while boosting energy metabolism as revealed in animal
      literature. RRE offers comprehensive treatment of stress symptoms and can prevent
      chronic stress and stress-related complications.

PMID- 29325482
TI  - Reply to letter to editor regarding: Correlation between uterine artery Doppler
      indices and menstrual irregularities among levonorgestrel-releasing intrauterine
      system and depot medroxyprogesterone acetate users: a prospective observational
      study.

PMID- 29325483
TI  - Characterization of Vaccination Policies for Attendance and Employment at
      Day/Summer Camps in New York State.
AB  - INTRODUCTION: New York state requires day/summer camps to keep immunization
      records for all enrolled campers and strongly recommends requiring vaccination
      for all campers and staff. The objective of this study was to characterize
      immunization requirements/recommendations for children/adolescents enrolled in
      and staff employed at day/summer camps in New York state. METHODS: An electronic
      hyperlink to a 9-question survey instrument was distributed via e-mail to 178
      day/summer camps located in New York state cities with a population size greater
      than 100 000 people. A follow-up telephone survey was offered to nonresponders.
      The survey instrument included questions pertaining to vaccination documentation
      policies for campers/staff and the specific vaccines that the camp
      required/recommended. Fisher's exact and Chi-square tests were used to analyze
      categorical data. RESULTS: Sixty-five day/summer camps responded to the survey
      (36.5% response rate): 48 (73.8%) and 23 (41.8%) camps indicated having a
      policy/procedure for documenting vaccinations for campers and staff,
      respectively. Camps that had a policy/procedure for campers were more likely to
      have a policy/procedure for staff ( P = .0007). Age-appropriate vaccinations that
      were required/recommended for campers by at least 80% of camps included: measles,
      mumps, and rubella (MMR), diphtheria, tetanus, and pertussis (DTaP), hepatitis B,
      inactivated/oral poliovirus (IPV/OPV), Haemophilus influenzae type b (Hib), and
      varicella. Age-appropriate vaccinations that were required/recommended for staff
      by at least 80% of camps included: DTaP, hepatitis B, IPV/OPV, MMR,
      meningococcus, varicella, Hib, and tetanus, diphtheria, and pertussis (Tdap).
      CONCLUSION: Vaccination policies at day/summer camps in New York state appear to
      be suboptimal. Educational outreach may encourage camps to strengthen their
      immunization policies, which may reduce the transmission of vaccine-preventable
      diseases.

PMID- 29325485
TI  - Hepatitis A immunisation need in nursing students in Turkey.
AB  - Hepatitis A is a worldwide vaccine-preventable infection. The aim of our study
      was to determine the serological status of hepatitis A virus (HAV) among first
      year nursing students in Turkey. A sample of 423 students was used and
      immunoglobulin G antibodies against HAV were determined quantitatively by enzyme
      linked immunosorbent assay on each. Overall, 84.6% had no immunity to HAV, making
      them at risk for HAV, and so susceptible to nosocomial transmission. Nursing
      students who work in high-risk wards must be vaccinated against hepatitis A.

PMID- 29325486
TI  - Intensive client-centred occupational therapy in the home improves older adults'
      occupational performance. Results from a Danish randomized controlled trial.
AB  - BACKGROUND: There is growing interest in enabling older adults' occupational
      performance. We tested whether 11 weeks of intensive client-centred occupational
      therapy (ICC-OT) was superior to usual practice in improving the occupational
      performance of home-dwelling older adults. METHODS: An assessor-masked randomized
      controlled trial among adults 60 + with chronic health issues, who received or
      applied for homecare services. Recruitment took place September 2012 to April
      2014. All participants received practical and personal assistance and meal
      delivery as needed. In addition, they were randomized to receive either a maximum
      22 sessions of occupation-based ICC-OT (N = 59) or to receive usual practice with
      a maximum three sessions of occupational therapy (N = 60). The primary outcome
      was self-rated occupational performance assessed with the Canadian Occupational
      Performance Measure (COPM). RESULTS: No important adverse events occurred. ICC-OT
      was accepted by 46 participants (88%), usual practice by 60 (100%). After 3
      months, the ICC-OT-group had improved 1.86 points on COPM performance; the Usual
      Practice group had improved 0.61 points. The between-group difference was
      statistically significant (95% confidence interval 0.50 to 2.02), t-test: p =
      0.001. CONCLUSIONS: ICC-OT improved older adults' occupational performance more
      effectively than usual practice. This result may benefit older adults and support
      programmatic changes.

PMID- 29325484
TI  - Risk of Erectile Dysfunction After Traumatic Brain Injury: A Nationwide
      Population-Based Cohort study in Taiwan.
AB  - INTRODUCTION: In our study, we aimed to investigate the association between a
      traumatic brain injury (TBI) and subsequent erectile dysfunction (ED). This is a
      population-based study using the claims dataset from The National Health
      Insurance Research Database. METHODS: We included 72,642 patients with TBI aged
      over 20 years, retrospectively, selected from the longitudinal health insurance
      database during 2000-2010, according to the ICD-9-CM. The control group consisted
      of 217,872 patients without TBI that were randomly chosen from the database at a
      ratio of 1:3, with age- and index year matched. Cox proportional hazards analysis
      was used to estimate the association between the TBI and subsequent ED. RESULTS:
      After a 10-year follow-up, the incidence rate of ED was higher in the TBI
      patients when compared with the non-TBI control group (24.66 and 19.07 per
      100,000, respectively). Patients with TBI had a higher risk of developing ED than
      the non-TBI cohort after the adjustment of the confounding factors, such as age,
      comorbidity, residence of urbanization and locations, seasons, level of care, and
      insured premiums (adjusted hazard ratio (HR) = 2.569, 95% CI [1.890, 3.492], p <
      .001). CONCLUSION: This is the first study using a comprehensive nationwide
      database to analyze the association of ED and TBI in the Asian population. After
      adjusted the confounding factors, patients with TBI have a significantly higher
      risk of developing ED, especially organic ED, than the general population. This
      finding might remind clinicians that it's crucial in early identification and
      treatment of ED in post-TBI patients.

PMID- 29325487
TI  - Use of TiO2 photocatalyst supported on residues of polystyrene packaging and its
      applicability on the removal of food dyes.
AB  - This work proposes the use of plastic residues, more specifically polystyrene
      packaging, to support TiO2, used as a photocatalyst in the degradation of
      erythrosine and Brilliant Blue food dyes. The scanning electron microscopy and
      Fourier transform infrared spectroscopy analyses exhibited the surface coating
      and the presence of TiO2 in the material, respectively. The
      UV/H2O2/TiO2((SP)supported) process was used in the preliminary study, given the
      high percentage of degradation, operational advantages and greater reductions in
      peaks related to the aromatic rings when compared to the other processes studied.
      For the factorial design, the highest efficiency was reached for 150 mg of TiO2,
      a H2O2 concentration of 11.2 mmol L-1 and pH of 5.0. These conditions were used
      in the degradation kinetics, which was rapid during the first 30 min, with the
      concentration of dyes in the solution reaching values close to zero after 180
      min. Based on the mechanism proposed, the pseudo-first order kinetic model
      presented the best adjustment to the experimental data. After treatment, the
      solution presented greater biodegradability and lower toxicity, verified by the
      lettuce seed germination test (Lactuca sativa). Thus, the
      UV/H2O2/TiO2((SP)supported) process showed great potential in the treatment of
      industrial effluents contaminated by these food dyes, as well as in reusing
      discarded polystyrene packaging to support the photocatalyst.

PMID- 29325488
TI  - Effects of adipokinetic hormone and its related peptide on maintaining hemolymph
      carbohydrate and lipid levels in the two-spotted cricket, Gryllus bimaculatus.
AB  - Adipokinetic hormone (AKH) regulates energy homeostasis in insects by mobilizing
      lipid and carbohydrate from the fat body. Here, using RNA sequencing data, we
      identified cDNAs encoding AKH (GbAKH) and its highly homologous hormone
      AKH/corazonin-related peptide (GbACP) in the corpora cardiaca of the two-spotted
      cricket, Gryllus bimaculatus. RT-PCR revealed that GbAKH and GbACP are
      predominantly expressed in the corpora cardiaca and corpora allata, respectively.
      Phylogenetic analysis confirmed that the identified GbAKH and GbACP belong to the
      clades containing other AKHs and ACPs, respectively. Injection of synthetic GbAKH
      and GbACP elevated hemolymph carbohydrate and lipid levels and reduced food
      intake significantly. In contrast, knockdown of GbAKH and GbACP by RNA
      interference increased the food intake, although hemolymph lipid level was not
      altered. Collectively, this study provides evidence that ACP regulates hemolymph
      carbohydrate and lipid levels in cricket, possibly collaborative contribution
      with AKH to the maintenance of energy homeostasis.

PMID- 29325490
TI  - Allocating less attention to central vision during vection is correlated with
      less motion sickness.
AB  - Visually induced motion sickness (VIMS) is a common discomfort response
      associated with vection-provoking stimuli. It has been suggested that
      susceptibility to VIMS depends on the ability to regulate visual performance
      during vection. To test this, 29 participants, with VIMS susceptibility assessed
      by Motion Sickness Susceptibility Questionnaire, were recruited to undergo three
      series of sustained attention to response tests (SARTs) while watching dot
      pattern stimuli known to provoke roll-vection. In general, SARTs performance was
      impaired in the central visual field (CVF), but improved in peripheral visual
      field (PVF), suggesting the reallocation of attention during vection. Moreover,
      VIMS susceptibility was negatively correlated with the effect sizes, suggesting
      that participants who were less susceptible to VIMS showed better performance in
      attention re-allocation. Finally, when trained to re-allocation attention from
      the CVF to the PVF, participants experienced more stable vection. Findings
      provide a better understanding of VIMS and shed light on possible preventive
      measures. Practitioner Summary: Allocating less visual attention to central
      visual field during visual motion stimulation is associated with stronger vection
      and higher resistance to motion sickness. Virtual reality application designers
      may utilise the location of visual tasks to strengthen and stabilise vection,
      while reducing the potential of visually induced motion sickness.

PMID- 29325489
TI  - Creating effective biocontainment facilities and maintenance protocols for
      raising specific pathogen-free, severe combined immunodeficient (SCID) pigs.
AB  - Severe combined immunodeficiency (SCID) is defined by the lack of an adaptive
      immune system. Mutations causing SCID are found naturally in humans, mice,
      horses, dogs, and recently in pigs, with the serendipitous discovery of the Iowa
      State University SCID pigs. As research models, SCID animals are naturally
      tolerant of xenotransplantation and offer valuable insight into research areas
      such as regenerative medicine, cancer therapy, as well as immune cell signaling
      mechanisms. Large-animal biomedical models, particularly pigs, are increasingly
      essential to advance the efficacy and safety of novel regenerative therapies on
      human disease. Thus, there is a need to create practical approaches to maintain
      hygienic severe immunocompromised porcine models for exploratory medical
      research. Such research often requires stable genetic lines for replication and
      survival of healthy SCID animals for months post-treatment. A further hurdle in
      the development of the ISU SCID pig as a biomedical model involved the
      establishment of facilities and protocols necessary to obtain clean SPF piglets
      from the conventional pig farm on which they were discovered. A colony of
      homozygous SCID boars and SPF carrier sows has been created and maintained
      through selective breeding, bone marrow transplants, innovative husbandry
      techniques, and the development of biocontainment facilities.

PMID- 29325491
TI  - Safety of outpatient percutaneous native renal biopsy in systemic autoimmune
      diseases: results from a monocentric cohort.

PMID- 29325492
TI  - Illness perception is significantly determined by depression and anxiety in
      systemic lupus erythematosus.
AB  - Objectives Illness perception is a cognitive representation influencing physical
      and psychological functioning and adherence in patients with rheumatic disease.
      Studies exploring illness perception in systemic lupus erythematosus (SLE) are
      still scarce and none of them have investigated factors determining illness
      perception. We aimed to assess illness perception and to identify psychological,
      clinical and sociodemographic factors that might influence illness perception in
      SLE. Methods The study involved 80 patients with SLE (87.5% women, mean age 41.56
      years). The Brief Illness Perception Questionnaire, State Trait Anxiety
      Inventory, Beck Depression Inventory, Pittsburgh Sleep Quality Index, Visual
      Analogue Scale-Pain and Fatigue Severity Scale were used. Clinical and
      sociodemographic data were collected via structured interview and medical files
      review. Results Illness perception was significantly positively correlated with
      anxiety, depression, sleep quality, fatigue and pain while it was not related to
      age, education, steroid treatment, disease duration and activity (SLEDAI) or
      organ damage (SLICC/ACR). Regression analysis revealed that state anxiety and
      depression explained 43% of illness perception variance. Cluster analysis
      identified three patient groups among which the middle-aged group had the most
      negative illness perception, the highest levels of anxiety, depression, pain and
      fatigue, and the poorest sleep quality. Conclusions The study has proved a
      significant relationship between negative illness perception and anxiety and
      depression. Patients reporting fatigue, poor sleep and pain might have special
      needs in terms of psychological intervention focused on negative illness
      perception and distress symptoms. Multidisciplinary care in managing SLE seems to
      be of great importance.

PMID- 29325493
TI  - Simulation-based evaluation of an in-vehicle smart situation awareness
      enhancement system.
AB  - Situation awareness (SA) constitutes a critical factor in road safety, strongly
      related to accidents. This paper describes the evaluation of a proposed SA
      enhancement system (SAES) that exploits augmented reality through a head-up
      display (HUD). Two SAES designs were evaluation (information rich vs. minimal
      information) using a custom-made simulator and the Situation Awareness Global
      Assessment Technique with performance and EEG measures. The paper describes the
      process of assessing the SA of drivers using the SAES, through a series of
      experiments with participants in a Cave Automatic Virtual Environment. The
      effectiveness of the SAES was tested in a within-group research design. The
      results showed that the information rich (radar-style display) was superior to
      the minimal (arrow hazard indicator) design and that both SAES improved drivers'
      SA and performance compared to the control (no HUD) design. Practitioner Summary:
      Even though driver situation awareness is considered as one of the leading causes
      of road accidents, little has been done to enhance it. The current study
      demonstrates the positive effect of a proposed situation awareness enhancement
      system on driver situation awareness, through an experiment using virtual
      prototyping in a simulator.

PMID- 29325494
TI  - A Bayesian approach for the identification of patient-specific parameters in a
      dialysis kinetic model.
AB  - Hemodialysis is the most common therapy to treat renal insufficiency. However,
      notwithstanding the recent improvements, hemodialysis is still associated with a
      non-negligible rate of comorbidities, which could be reduced by customizing the
      treatment. Many differential compartment models have been developed to describe
      the mass balance of blood electrolytes and catabolites during hemodialysis, with
      the goal of improving and controlling hemodialysis sessions. However, these
      models often refer to an average uremic patient, while on the contrary the
      clinical need for customization requires patient-specific models. In this work,
      we assume that the customization can be obtained by means of patient-specific
      model parameters. We propose and validate a Bayesian approach to estimate the
      patient-specific parameters of a multi-compartment model, and to predict the
      single patient's response to the treatment, in order to prevent intra-dialysis
      complications. The likelihood function is obtained by means of a discretized
      version of the multi-compartment model, where the discretization is in terms of a
      Runge-Kutta method to guarantee convergence, and the posterior densities of model
      parameters are obtained through Markov Chain Monte Carlo simulation. Results show
      fair estimations and the applicability in the clinical practice.

PMID- 29325496
TI  - Maternal Thyrotropin Receptor Antibody Concentration and the Risk of Fetal and
      Neonatal Thyrotoxicosis: A Systematic Review.
AB  - BACKGROUND: In pregnant women with Graves' disease, maternal thyrotropin receptor
      antibodies (TRAb) can cross the placenta and induce fetal or neonatal
      thyrotoxicosis. Symptoms of fetal thyrotoxicosis are tachycardia, intrauterine
      growth restriction, and intra-uterine death. Recommendations on an upper limit of
      TRAb concentrations below which intensive fetal monitoring can be safely omitted
      vary between different guidelines. The objective of this study was to define an
      evidence-based cutoff level for maternal TRAb necessitating additional fetal
      monitoring during pregnancy. METHODS: A literature search was performed to
      identify studies on pregnant women with Graves' disease and fetal and/or neonatal
      thyrotoxicosis. Only studies that reported TRAb were included. RESULTS: From a
      total of 229 identified titles, 20 articles could be included in the analysis. A
      total of 53 cases of fetal and/or neonatal thyrotoxicosis were described. The
      lowest level of maternal TRAb leading to neonatal thyrotoxicosis was 4.4 U/L,
      which corresponds to 3.7 times the upper limit of normal. The level of evidence
      for this threshold is moderate to low. CONCLUSION: In women with Graves' disease,
      intensive fetal monitoring is recommended when maternal TRAb concentrations are
      >3.7 times the upper limit of normal. This cutoff level should be interpreted
      with caution, since evidence is limited.

PMID- 29325495
TI  - Management of cancer-associated venous thromboembolism - a case-based practical
      approach.
AB  - In patients with solid tumours or haematological malignancies, venous
      thromboembolism (VTE) is a leading cause of death and significantly contributes
      to morbidity and healthcare resource utilization. Current practice guidelines
      recommend long-term anticoagulation with low-molecular-weight heparin (LMWH) as
      the treatment of choice for cancer-associated VTE, based on clinical trial data
      showing an overall improved safety and efficacy profile of LMWH compared to
      vitamin K antagonists. However, several open questions remain, e. g. with regard
      to the intensity and duration of LMWH therapy; moreover, recent real-world
      evidence indicates that adherence to parenteral anticoagulation with LMWH over
      the course of treatment is poor in clinical practice. In this regard, the direct
      oral factor Xa or thrombin inhibitors (DOACs) have emerged as potential
      alternatives in the management of patients with cancer-associated VTE, albeit
      findings from randomized controlled studies with a direct head-to-head comparison
      of DOACs with LMWH, the current standard of care, are still lacking. Based on the
      case of a lymphoma patient experiencing symptomatic pulmonary embolism during
      immunochemotherapy, this article aims at both highlighting the current state-of
      the-art approach to cancer-associated VTE and pointing out some of the
      unresolved, controversial issues clinicians have to face when taking care of
      haematology and oncology patients with already established or with high risk of
      developing VTE. These issues include the management of patients with incidental
      pulmonary embolism or thrombocytopenia, the use of DOACs, and the initiation of
      pharmacological thromboprophylaxis in non-surgical cancer patients.

PMID- 29325498
TI  - The structure of the General Health Questionnaire (GHQ-12): two meta-analytic
      factor analyses.
AB  - The General Health Questionnaire (GHQ-12) is a popular measure of psychological
      distress. Despite its widespread use, an ongoing controversy pertains to its
      internal structure. Although the GHQ-12 was originally constructed to capture a
      unitary construct, empirical studies identified different factor structures.
      Therefore, this study examined the dimensionality of the GHQ-12 in two
      independent meta-analyses. The first meta-analysis used summary data published in
      38 primary studies (total N = 76,473). Meta-analytic exploratory factor analyses
      identified two factors formed by negatively and positively worded items. The
      second meta-analysis included individual responses of 410,640 participants from
      84 independent samples. Meta-analytic confirmatory factor analyses corroborated
      the two-dimensional structure of the GHQ-12. However, bifactor modelling showed
      that most of the variance was explained by a general factor. Therefore, subscale
      scores reflected rather limited unique variance. Overall, the two meta-analyses
      demonstrated that the GHQ-12 is essentially unidimensional. It is not recommended
      to use and interpret subscale scores because they primarily reflect general
      mental health rather than distinct constructs.

PMID- 29325497
TI  - Impact and Moderating Variables of an Intervention Promoting Physical Activity
      Among Children: Results From a Pilot Study.
AB  - This pilot study pursued three objectives: to assess the effect of a 1-month
      multilevel intervention on the PA of children, to assess the impact of the
      intervention on the theory of planned behavior (TPB) variables, and to evaluate
      the extent to which the impact of the intervention on PA and TPB variables varied
      according to personal (i.e., gender and age) and situational (i.e., class and
      school) moderating variables. Children were aged 7 to 11 years ( n = 306).
      Analyses revealed a significant increase of PA practice and TPB variables ( ps <
      .001). Age (i.e., being a younger child) was associated with a higher increase on
      attitude and perceived control ( ps < .01). The class or the school levels
      explained a meaningful variance in the evolution of PA or TPB variables
      (intraclass correlation coefficients > .10). The present study reports the
      interest and feasibility of a multilevel intervention to increase PA and TPB
      variables in children.

PMID- 29325499
TI  - Insights and barriers to clinical use of serotonin transporter pharmacogenetics
      in antidepressant therapy.

PMID- 29325500
TI  - Images in Vascular Medicine: Cystic adventitial disease involving external iliac
      vein: A rare cause of unilateral limb swelling.

PMID- 29325501
TI  - Venous hemodynamics assessed with air plethysmography in legs with lymphedema.
AB  - This study was conducted to identify specific abnormalities using the results
      from air plethysmography in legs with lymphedema. A routine air plethysmography
      exercise protocol was performed in 31 patients with unilateral leg lymphedema,
      and the results were compared with those of 53 patients with unilateral great
      saphenous vein reflux and 15 normal subjects. The venous filling index in legs
      with lymphedema (2.1 +/- 1.2 mL/sec) was smaller than in legs with great
      saphenous vein reflux (6.4 +/- 4.1 mL/sec, p < 0.05), but was not different from
      that in normal legs (1.9 +/- 1.2 mL/sec). The ejection fraction was similar in
      all groups. The residual volume fraction in legs with lymphedema (35 +/- 32%) was
      larger than that in normal subjects (13 +/- 23%, p < 0.05), but was not
      significantly different from that in the contralateral leg of the lymphedema
      patients (32 +/- 27%). In conclusion, we found no specific air plethysmography
      findings in uncomplicated lymphedema.

PMID- 29325502
TI  - REHEARSAL Using Patient-Specific Simulation to Improve Endovascular Efficiency.
AB  - OBJECTIVE: To determine whether rehearsal using patient-specific information
      loaded onto an endovascular simulator prior to carotid stenting improves
      procedural efficiency and outcomes. METHODS: Patients scheduled for carotid
      artery stenting who had adequate preoperative computed tomography (CT) imaging
      were considered for enrollment. After obtaining informed consent, patients were
      randomized to control versus rehearsal groups. Those in the rehearsal group had
      their CT scans loaded into an endovascular simulator (Angio Mentor) followed by
      case rehearsal by the attending on the simulator within 24 hours prior to the
      procedure; control patients underwent routine carotid stenting without rehearsal.
      Contrast usage, fluoroscopy time, and timing of procedural steps were recorded by
      a blinded observer during the actual case to determine benefit. RESULTS: Fifteen
      patients were enrolled, with 6 patients randomized to the rehearsal group and 9
      to the control. All measures showed improvement in the rehearsal group: Mean
      contrast volume (59.2 vs 76.9 mL), fluoroscopy time (11.4 vs 19.4 minutes),
      overall operative time (31.9 vs 42.5 minutes), time to common carotid sheath
      placement (17.0 vs 23.3 minutes), and total carotid sheath dwell time (14.9 vs
      19.2 minutes) were all lower (more favorable) in the rehearsal group. The study
      was terminated early due to the lack of simulator access, and all P values were
      thus greater than .05 due to the lack of power. No strokes or other adverse
      events occurred in either group. CONCLUSION: Case-specific simulator rehearsal
      using patient-specific imaging prior to carotid stenting is associated with
      numerically less contrast usage, operative time, and radiation exposure, although
      this study was underpowered.

PMID- 29325503
TI  - Immunogenetics of prostate cancer: a still unexplored field of study.
AB  - The immune system is a double-edged sword with regard to the prostate cancer
      (PCa) battle. Immunogenetics, the study of the potential role of immune-related
      polymorphisms, is taking its first steps in the treatment of this malignancy.
      This review summarizes the most recent papers addressing the potential of
      immunogenetics in PCa, reporting immune-related polymorphisms associated with
      tumor aggressiveness, treatment toxicity and patients' prognosis. With some
      peculiarities, RNASEL, IL-6, IL-10, IL-1beta and MMP7 have arisen as the most
      significant biomarkers in PCa treatment and management, having a potential
      clinical role. Validation prospective clinical studies are required to translate
      immunogenetics into precision treatment of PCa.

PMID- 29325505
TI  - The relationship between cholesterol level and Alzheimer's disease-associated APP
      proteolysis/Abeta metabolism.
AB  - Globally, Alzheimer's disease (AD) is the most prevalent neurodegenerative
      disease in the elderly population, the hallmark of which is amyloid beta (Abeta)
      peptide. Energy metabolism and AD pathogenesis are believed to influence one
      another. Different cholesterol levels are thought to influence various steps in
      neurotoxic Abeta generation, including amyloid precursor protein (APP)
      proteolysis and the corresponding activities of alpha-, beta-, and gamma
      secretases. In addition, cholesterol has been proved to mediate Abeta metabolism,
      such as its fibrillation, transportation, degradation, and clearance processes.
      The current review discusses in detail the intimate interaction between the
      cholesterol level and the various aspects of APP proteolysis and Abeta
      metabolism.

PMID- 29325504
TI  - Platelet-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio, and platelet
      indices in patients with acute deep vein thrombosis.
AB  - BACKGROUND: Inflammation is associated with an increased risk of thrombotic
      events and complete blood count (CBC) is an easily measured test. The purpose of
      this study was to evaluate the value of CBC relative parameters including mean
      platelet volume (MPV), platelet-to-lymphocyte ratio (PLR), mean platelet volume
      to-lymphocyte ratio (MPVLR), and neutrophil-to-lymphocyte ratio (NLR) for
      patients with acute deep vein thrombosis (DVT). PATIENTS AND METHODS: A total of
      115 patients with unprovoked DVT of the lower extremities and 105 controls were
      recruited in this study. Blood samples were drawn from all participants to obtain
      the concentrations of CBCs and D-dimers. RESULTS: MPVs (P = 0.044), PLRs (P =
      0.005), MPVLRs (P = 0.001), and NLRs (P < 0.0001) were significantly higher in
      acute DVT patients compared to controls. The MPV was inversely correlated with
      platelet count (P < 0.0001) and the NLR was positively associated with D-dimers
      (P = 0.002) and the PLR (P < 0.0001). Notably, on multivariate logistic
      regression analysis, NLRs and D-dimers were independent risk factors of acute DVT
      (OR: 1.889, P = 0.024; OR: 1.009, P < 0.0001, respectively). CONCLUSIONS: MPV,
      PLR, MPVLR, and NLR have potential diagnostic values for patients with unprovoked
      DVT. NLR is an independent risk factor related to DVT.

PMID- 29325506
TI  - Clinical Impact of Detectable Antithyroglobulin Antibodies Below the Reference
      Limit (Borderline) in Patients with Papillary Thyroid Carcinoma with Undetectable
      Serum Thyroglobulin and Normal Neck Ultrasonography After Ablation: A Prospective
      Study.
AB  - BACKGROUND: Interference of antithyroglobulin antibodies (TgAb) with serum
      thyroglobulin (Tg) can occur even at detectable TgAb concentrations below the
      reference limit (borderline TgAb). Thus, borderline TgAb is considered as TgAb
      positivity in patients with thyroid cancer. This prospective study evaluated
      patients with papillary thyroid carcinoma with undetectable Tg and normal neck
      ultrasonography (US) after total thyroidectomy and ablation with 131I, and
      compared tumor persistence/recurrence and long-term Tg and TgAb behavior in those
      with borderline versus undetectable TgAb. METHODS: A total of 576 patients were
      evaluated, divided into two groups: group A with undetectable TgAb (n = 420), and
      group B with borderline TgAb (n = 156). RESULTS: Groups A and B were similar in
      terms of patient and tumor characteristics. The time of follow-up ranged from 24
      to 120 months. During follow-up, 11 (2.6%) patients in group A and 5 (3.2%) in
      group B developed a recurrence (p = 0.77). In group A, recurrences occurred in
      9/390 patients who continued to have undetectable TgAb and in 1/9 patients who
      progressed to borderline TgAb. In group B, recurrences were detected in 1/84
      patients who progressed to have undetectable TgAb, in 1/45 who still had
      borderline TgAb, and in 3/12 who developed elevated TgAb. In the presence of Tg
      levels <0.2 ng/mL, recurrences were detected in 2/486 patients with undetectable
      TgAb, in 0/67 with borderline TgAb, and in 3/12 with elevated TgAb. The results
      of post-therapy whole-body scanning (RxWBS) of 216 patients with Tg <=0.2 ng/mL
      and normal US at the time of ablation were also analyzed. In low-risk patients,
      none of the 40 patients with borderline TgAb and none of the 94 with undetectable
      TgAb exhibited ectopic uptake on RxWBS. In intermediate-risk patients, lymph node
      metastases were detected by RxWBS in 1/25 (4%) with borderline TgAb and in 2/57
      (3.5%) with undetectable TgAb. CONCLUSIONS: The results suggest that among low-
      or intermediate-risk patients with undetectable Tg and normal US after
      thyroidectomy, those with borderline TgAb are at no greater risk of tumor
      persistence or recurrence than those with undetectable TgAb. When undetectable Tg
      levels persist, recurrence should be suspected in the case of a TgAb elevation
      above the reference limit.

PMID- 29325507
TI  - Research Collaboration in a Communication Rights Campaign: Lessons Learned.
AB  - In building public support for social change, activists in communities of color
      routinely approach broader audiences via news media. Communities of color,
      however, routinely face disparities that limit their access to media including
      local news media outlets. This lack of access mirrors inequalities in political,
      social, and economic arenas and can slow public awareness campaigns to address
      disparities in health, environmental, and other quality-of-life issues. I
      describe two community-based collaborative action research studies that
      documented and challenged how local television newscasts underrepresented and
      misrepresented three communities of color in Boston. The linkage between
      communication rights and campaigns to address quality-of-life issues is
      presented, as well as unresolved challenges in the collaborative research
      process. The study has implications for environmental health campaigns.

PMID- 29325508
TI  - Mesh nebulizers have become the first choice for new nebulized pharmaceutical
      drug developments.
AB  - In the 24 years since first being marketed, the mesh nebulizer has been developed
      by five main manufacturers into a viable solution for the delivery of high-value
      nebulized drugs. Mesh nebulizers provide increased portability, convenience and
      energy efficiency along with similar lung deposition and increased ease of use
      compared with jet nebulizers. An analysis of EU and US clinical trial databases
      has shown that mesh nebulizers are now preferred over jet nebulizers for clinical
      trials sponsored by pharmaceutical companies. The results show a strong
      preference for the use of mesh nebulizers in trials involving high cost and niche
      therapy areas. Built-in capability to optimize the way patients use their mesh
      nebulizer and manage their disease will further increase uptake. [Formula: see
      text].

PMID- 29325509
TI  - Terbinafine hydrochloride nail lacquer for the management of onychomycosis:
      formulation, characterization and in vitro evaluation.
AB  - AIM: The present investigation's intention was to develop an optimized nail
      lacquer (NL) for the management of onychomycosis. MATERIALS & METHODS: The NL was
      optimized statistically adopting 32 full factorial design having different
      polymer ratios and solvent ratios. The formulations were assessed for drug
      permeation drying time and peak adhesive strength of the film. Characterization
      was done using techniques including attenuated total reflectance-Fourier
      transform infrared spectroscopy (ATR-FTIR), scanning electron microscopy (SEM),
      differential scanning calorimetry (DSC), x-ray diffraction (XRD), etc. RESULTS &
      CONCLUSION: The formulation that had 1:1 polymer ratio and 80:20 solvent ratio
      was chosen as the optimized formulation. In vitro permeation studies showed
      better penetration (~3.25-fold) as well as retention (~11-fold) of the optimized
      NL formulation in the animal hoof as compared with the commercial formulation.
      The findings of in vitro and ex vivo studies elucidated the potential of the
      optimized formulation. [Formula: see text].

PMID- 29325510
TI  - Albendazole nanocrystals with improved pharmacokinetic performance in mice.
AB  - AIM: Albendazole (ABZ) is a broad-spectrum antiparasitic agent with poor aqueous
      solubility, which leads to poor/erratic bioavailability and therapeutic failures.
      Here, we aimed to produce a novel formulation of ABZ nanocrystals (ABZNC) and
      assess its pharmacokinetic performance in mice. Results/methodology: ABZNC were
      prepared by high-pressure homogenization and spray-drying processes. Redispersion
      capacity and solid yield were measured in order to obtain an optimized product.
      The final particle size was 415.69+/-7.40 nm and the solid yield was 72.32%. The
      pharmacokinetic parameters obtained in a mice model for ABZNC were enhanced (p <
      0.05) with respect to the control formulation. CONCLUSION: ABZNC with improved
      pharmacokinetic behavior were produced by a simple, inexpensive and potentially
      scalable methodology.

PMID- 29325511
TI  - Recent advances in topical nano drug-delivery systems for the anterior ocular
      segment.
AB  - Over the past decade, there has been a rise in the number of clinical cases of
      moderate to severe anterior segment ocular diseases. Conventional topical
      ophthalmic formulations have several limitations - to address which, novel drug
      delivery systems are needed. Additionally, formidable physiological barriers
      limit ocular bioavailability through the topical route of application. During the
      last decade, various nano-scaled ocular drug-delivery strategies have been
      reported. Some of these exploratory, topical, noninvasive approaches have shown
      promise in improving penetration into the anterior segment tissues of the eye. In
      this article, we review the available literature with respect to the safety,
      efficiency and effectiveness of these nano systems.

PMID- 29325512
TI  - An industry update: the latest developments in therapeutic delivery.
AB  - The present industry update covers the period 1 October-31 October 2017, with
      information sourced from company press releases, regulatory and patent agencies
      as well as scientific literature. While the corporate news in October was
      traditionally dominated by the announcement of the third quarter results, with
      most of them showing market and revenue growth but also an increasing number of
      initial public offerings after years of slower financial development, we also saw
      trends continuing toward an increasing number of convergences of drugs with
      nanotechnology, devices and 21st century information technology. Whether it is
      using E Ink's 'Smart Patch', AstraZeneca's autoinjector, Elektrofi's Elektroject
      suspensions or NanOlogy's NanoPac, there is an ever increasing number of
      combinations dof devices, drugs and applications reaching, more and more the
      clinic and the market. Controlled release is another feature increasingly
      addressed by many of the above innovations. For example, the drug-loaded x-ray
      imageable microscopic beads that have been developed by researchers at UCL Cancer
      Institute (London, UK) take this one step further in order to pursue local,
      controlled and in situ validated local delivery.

PMID- 29325514
TI  - Editor's Note.

PMID- 29325513
TI  - Use of methylene blue in the prevention of recurrent intra-abdominal
      postoperative adhesions.
AB  - Objective To evaluate the efficacy of methylene blue in preventing recurrent
      symptomatic postoperative adhesions. Methods Patients with a history of >2
      surgeries for intra-abdominal adhesion-related complications were selected for
      this study. Adhesiolysis surgery was subsequently performed using administration
      of 1% methylene blue. The follow-up period was 28.5 +/- 11.1 months. Results Data
      were available from 20 patients (seven men and 13 women) whose mean +/- SD age
      was 51.2 +/- 11.4 years. Adhesions took longer to become symptomatic after the
      first abdominal surgery when the initial pathology was malignant compared with
      benign. However, the recurrence of adhesions after a previous adhesiolysis
      surgery had a similar time onset regardless of the initial disease. Following
      adhesiolysis surgery with methylene blue, the majority of patients did not
      present with symptoms associated with adhesion complications (i.e., chronic
      abdominal pain, bowel obstruction) for the length of the follow-up period.
      Conclusions The use of methylene blue during adhesiolysis surgery appears to
      reduce the recurrence of adhesion-related symptoms, suggesting a beneficial
      effect in the prevention of adhesion formation.

PMID- 29325515
TI  - Safer chairs for elderly patients: design evaluation using electromyography and
      force measurement.
AB  - A vast majority of patient fall events in hospitals involve the elderly. In
      inpatient care settings, despite the risk of fall, patients are encouraged to
      leave their bed, move around their room, and sit on their chair to progress in
      their healing. Despite the vital role of patient chair design in improving
      recovery, few studies have examined the ergonomic requirements of safe patient
      chairs. This study examined the impact of manipulating horizontal and vertical
      positions of armrests in a test chair on required physical effort during Stand-to
      Sit-to-Stand (St-Si-St) transitions among 15 elderly women. Physical effort was
      measured using: (1) surface electromyography (sEMG); (2) force measurement by
      load cells; (3) video recording. Findings showed non-linear patterns of change in
      required physical effort due to changes in armrests' height and distance. It was
      also found that minimum effort is associated with armrests higher and farther
      apart than those in typical patient chairs. Practitioner Summary: Safe chairs are
      essential for inpatient recovery, yet their ergonomic features are not
      investigated. Impact of changes in chair armrests on required physical effort was
      examined using electromyography, force measurement and video recording. Armrests
      higher and farther apart than those in typical patient chairs may be safer for
      elderly patients.

PMID- 29325516
TI  - Brucellosis remains a neglected disease in the developing world: a call for
      interdisciplinary action.
AB  - BACKGROUND: Brucellosis is an endemic zoonotic disease in most of the developing
      world that causes devastating losses to the livestock industry and small-scale
      livestock holders. Infected animals exhibit clinical signs that are of economic
      significance to stakeholders and include reduced fertility, abortion, poor weight
      gain, lost draught power, and a substantial decline in milk production. In
      humans, brucellosis typically manifests as a variety of non-specific clinical
      signs. Chronicity and recurring febrile conditions, as well as devastating
      complications in pregnant women are common sequelae. DISCUSSION: In regions where
      the disease is endemic, brucellosis has far-reaching and deleterious effects on
      humans and animals alike. Deeply entrenched social misconceptions and fear of
      government intervention contribute to this disease continuing to smolder
      unchecked in most of the developing world, thereby limiting economic growth and
      inhibiting access to international markets. The losses in livestock productivity
      compromise food security and lead to shifts in the cognitive competency of the
      working generation, influence the propagation of gender inequality, and cause
      profound emotional suffering in farmers whose herds are affected. The acute and
      chronic symptoms of the disease in humans can result in a significant loss of
      workdays and a decline in the socioeconomic status of infected persons and their
      families from the associated loss of income. The burden of the disease to society
      includes significant human healthcare costs for diagnosis and treatment, and non
      healthcare costs such as public education efforts to reduce disease transmission.
      CONCLUSION: Brucellosis places significant burdens on the human healthcare system
      and limits the economic growth of individuals, communities, and nations where
      such development is especially important to diminish the prevalence of poverty.
      The implementation of public policy focused on mitigating the socioeconomic
      effects of brucellosis in human and animal populations is desperately needed.
      When developing a plan to mitigate the associated consequences, it is vital to
      consider both the abstract and quantifiable effects. This requires an
      interdisciplinary and collaborative, or One Health, approach that consists of
      public education, the development of an infrastructure for disease surveillance
      and reporting in both veterinary and medical fields, and campaigns for control in
      livestock and wildlife species.

PMID- 29325517
TI  - A cluster randomised controlled trial evaluating the effectiveness and cost
      effectiveness of the daily mile on childhood obesity and wellbeing; the
      Birmingham daily mile protocol.
AB  - BACKGROUND: Childhood obesity prevention is a public health priority. Children
      spend a large proportion of their waking time in school; therefore this is an
      appropriate setting to implement obesity prevention initiatives. Anecdotal
      reports suggest that implementing The Daily Mile in schools has had positive
      effects on childhood obesity, academic attainment and wellbeing. This trial aims
      to measure the effectiveness of The Daily Mile for improving health and
      wellbeing. METHODS: This protocol describes a cluster randomised controlled trial
      (RCT) in 40 primary schools located in Birmingham, UK. Eligible participants are
      children in years 3 (aged 7-8) and 5 (aged 9-10). The study compares The Daily
      Mile (intervention) to usual practice (control) in relation to health and
      wellbeing. The Daily Mile intervention involves an additional 15 min of running
      or walking integrated into the school day, throughout a 12 month study period.
      The primary clinical outcome is body mass index (BMI) z-scores at 12 months
      following introduction of the intervention. The cost per Quality Adjusted Life
      Year (QALY) is the primary outcome of the economic evaluation. Secondary outcomes
      include wellbeing, physical fitness and teacher reported academic attainment.
      DISCUSSION: This study is the first RCT investigating the clinical and cost
      effectiveness of The Daily Mile. A range of outcomes will be measured to evaluate
      the broader wellbeing and academic benefits in addition to clinical outcomes
      typically measured in childhood obesity prevention trials. The intervention is
      simple and low-cost, therefore if the benefits are demonstrated it has enormous
      potential to influence future policy. TRIAL REGISTRATION: ISRCTN: 12698269 . Date
      protocol registered 27th October 2016.

PMID- 29325518
TI  - Experiences of gestational diabetes and gestational diabetes care: a focus group
      and interview study.
AB  - BACKGROUND: Gestational diabetes mellitus (GDM) is an increasingly common
      condition of pregnancy. It is associated with adverse fetal, infant and maternal
      outcomes, as well as an increased risk of GDM in future pregnancies and type 2
      diabetes for both mother and offspring. Previous studies have shown that GDM can
      result in an emotionally distressing pregnancy, but there is little research on
      the patient experience of GDM care, especially of a demographically diverse UK
      population. The aim of this research was to explore the experiences of GDM and
      GDM care for a group of women attending a large diabetes pregnancy unit in
      southeast London, UK, in order to improve care. METHODS: Framework analysis was
      used to support an integrated analysis of data from six focus groups with 35
      women and semi-structured interviews with 15 women, held in 2015. Participants
      were purposively sampled and were representative of the population being studied
      in terms of ethnicity, age, deprivation score and body mass index (BMI). RESULTS:
      We identified seven themes: the disrupted pregnancy, projected anxiety,
      reproductive asceticism, women as baby machines, perceived stigma, lack of shared
      understanding and postpartum abandonment. These themes highlight the often
      distressing experience of GDM. While most women were grateful for the intensive
      support they received during pregnancy, the costs to their personal autonomy were
      high. Women described feeling valued solely as a means to produce a healthy
      infant, and felt chastised if they failed to adhere to the behaviours required to
      achieve this. This sometimes had an enduring impact to the potential detriment of
      women's long-term psychological and physical health. CONCLUSIONS: This study
      reveals the experiences of a demographically diverse group of patients with GDM,
      reflecting findings from previous studies globally and extending analysis to the
      context of improving care. Healthcare delivery may need to be reoriented to
      improve the pregnancy experience and help ensure women are engaged and attentive
      to their own health, particularly after birth, without compromising clinical
      pregnancy outcomes. Areas for consideration in GDM healthcare include: improved
      management of emotional responses to GDM; a more motivational approach;
      rethinking the medicalisation of care; and improved postpartum care.

PMID- 29325519
TI  - Providers' preferences for pediatric oral health information in the electronic
      health record: a cross-sectional survey.
AB  - BACKGROUND: The majority of primary care physicians support integration of
      children's oral health promotion and disease prevention into their practices but
      can experience challenges integrating oral health services into their workflow.
      Most electronic health records (EHRs) in primary care settings do not include
      oral health information for pediatric patients. Therefore, it is important to
      understand providers' preferences for oral health information within the EHR. The
      objectives of this study are to assess (1) the relative importance of various
      elements of pediatric oral health information for primary care providers to have
      in the EHR and (2) the extent to which practice and provider characteristics are
      associated with these information preferences. METHODS: We surveyed a sample of
      primary care physicians who conducted Medicaid well-child visits in North
      Carolina from August - December 2013. Using descriptive statistics, we analyzed
      primary care physicians' oral health information preferences relative to their
      information preferences for traditional preventive aspects of well-child visits.
      Furthermore, we analyzed associations between oral health information preferences
      and provider- and practice-level characteristics using an ordinary least squares
      regression model. RESULTS: Fewer primary care providers reported that pediatric
      oral health information is "very important," as compared to more traditional
      elements of primary care information, such as tracking immunizations. However,
      the majority of respondents reported some elements of oral health information as
      being very important. Also, we found positive associations between the percentage
      of well child visits in which oral health screenings and oral health referrals
      are performed and the reported importance of having pediatric oral health
      information in the EHR. CONCLUSIONS: Incorporating oral health information into
      the EHR may be desirable for providers, particularly those who perform oral
      health screenings and dental referrals.

PMID- 29325520
TI  - Factors associated with low patient satisfaction in out-of-hours primary care in
      Denmark - a population-based cross-sectional study.
AB  - BACKGROUND: Low patient satisfaction with the quality of out-of-hours primary
      care (OOH-PC) has been linked with several individual and organizational factors.
      However, findings have been ambiguous and may not apply to the Danish out-of
      hours (OOH) setting in which general practitioners (GPs) perform the initial
      telephone triage. This study aimed to identify patient-related, GP-related and
      organizational factors associated with low patient satisfaction. METHODS: The
      study was based on data from a 1-year population-based survey of OOH-PC (LV-KOS)
      in the Central Denmark Region in 2010-2011. GPs on OOH duty completed an
      electronic questionnaire in the OOH computer system, and the registered patients
      received a subsequent postal questionnaire focusing on contact evaluation,
      waiting time, demographic characteristics and general self-perceived health.
      Associations were analysed using multivariable logistic regression with
      dissatisfaction as the dependent variable. RESULTS: The patient response rate was
      50.6%. For all contact types, 82.5% of the patients were satisfied with the OOH
      PC service. More patients were dissatisfied with telephone consultations than
      with clinic consultations or home visits (8.5% vs. 6.0% and 4.3%, respectively).
      Contacts assessed by the GP as 'not severe' were associated with dissatisfaction
      for telephone consultations and home visits. Poor general self-perceived health
      was associated with dissatisfaction for all contact types. Living in urban areas
      was associated with dissatisfaction for telephone consultations, while
      unacceptable waiting time was associated with dissatisfaction for all contact
      types. CONCLUSIONS: We found a high level of patient satisfaction with the OOH-PC
      service. The only factors affecting patient satisfaction across all contact types
      were unacceptable waiting time and poor general self-perceived health. For the
      other investigated factors, patient satisfaction depended on the type of contact.
      Generally, patients contacting for GP-assessed non-severe health problem and
      patients living in urban areas were more dissatisfied.

PMID- 29325521
TI  - Adjuvant treatment of resectable biliary tract cancer with cisplatin plus
      gemcitabine: A prospective single center phase II study.
AB  - BACKGROUND: Biliary tract cancer (BTC) is a dismal disease, even after curative
      intent surgery. We conducted this prospective, non-randomized phase II study to
      evaluate the feasibility and efficacy of cisplatin and gemcitabine as adjuvant
      treatment in patients with resected BTC. METHODS: Patients initially received
      gemcitabine 1000 mg/m2 alone on days 1, 8 and 15 every 28-days for a total of six
      cycles (single agent cohort), and after protocol amendment a combination therapy
      with gemcitabine 1000 mg/m2 and cisplatin 25 mg/m2 on days 1 and 8 was
      administered every 21 days for a total of eight cycles (combined regimen cohort).
      Treatment was planned to start within eight weeks after curative intent
      resection. Adverse events, disease-free survival and overall survival were
      assessed. RESULTS: Overall 30 patients were enrolled in the study from August
      2008 and last patient was enrolled at 2nd December 2014. The follow-up of the
      patients ended at 31st December 2016. The first 9 patients received single-agent
      gemcitabine. The interim analysis met the predefined feasibility criteria and,
      from September 2010 on, the second group of 21 patients received the combination
      of cisplatin plus gemcitabine. In the single-agent cohort with gemcitabine the
      median relative dose intensity (RDI) was 100% (IQR 88.3-100). Patients treated
      with the combination cisplatin-gemcitabine received an overall median RDI of 100%
      (IQR 50-100) for cisplatin and 100% (IQR 75-100) for gemcitabine respectively.
      The most significant non-hematological adverse events (grade 3 or 4) were fatigue
      (20%), infections during neutropenia (10%), and two cases of biliary sepsis (7%).
      Abnormal liver function was seen in 10% of the patients. One patient died due to
      infectious complications during treatment with cisplatin and gemcitabine. The
      median disease-free survival (DFS) was 14.9 months (95% CI 0-33.8) with a
      corresponding 3-year DFS of 43.1 +/- 9.1%. The median overall survival (OS) was
      40.6 months (95% CI 18.8-62.3) with a 3-year OS of 55.7 +/- 9.2%. No
      statistically significant differences in survival were seen between the two
      treatment cohorts. CONCLUSION: Adjuvant chemotherapy with gemcitabine with or
      without cisplatin was well tolerated and resulted in promising survival of the
      patients. TRIAL REGISTRATION: The study was retrospectively registered on 25th
      June 2009 at clinicaltrials.gov ( NCT01073839 ).

PMID- 29325522
TI  - Correction to: Relatively frequent switching of transcription start sites during
      cerebellar development.
AB  - CORRECTION: The authors of the original article [1] would like to recognize the
      critical contribution of core members of the FANTOM5 Consortium, who played the
      critical role of HeliScopeCAGE sequencing experiments, quality control of tag
      reads and processing of the raw sequencing data.

PMID- 29325523
TI  - Fanconi anemia with sun-sensitivity caused by a Xeroderma pigmentosum-associated
      missense mutation in XPF.
AB  - BACKGROUND: Fanconi anemia (FA) is an inherited genomic instability disorder with
      congenital and developmental abnormalities, bone marrow failure and
      predisposition to cancer early in life, and cellular sensitivity to DNA
      interstrand crosslinks. CASE PRESENTATION: A fifty-one-year old female patient,
      initially diagnosed with FA in childhood on the basis of classic features and
      increased chromosomal breakage, and remarkable sun-sensitivity is described. She
      only ever had mild haematological abnormalities and no history of malignancy. To
      identify and characterise the genetic defect in this lady, who is one of the
      oldest reported FA patients, we used whole-exome sequencing for identification of
      causative mutations, and functionally characterized the cellular phenotype.
      Detection of the novel splice site mutation c.793-2A > G and the previously
      described missense mutation c.1765C > T (p.Arg589Trp) in XPF/ERCC4/FANCQ assign
      her as the third individual of complementation group FA-Q. Ectopic expression of
      wildtype, but not mutant, XPF/ERCC4/FANCQ, in patient-derived fibroblasts rescued
      cellular resistance to DNA interstrand-crosslinking agents. Patient derived FA-Q
      cells showed impaired nuclear excision repair capacity. However, mutated
      XPF/ERCC4/FANCQ protein in our patient's cells, as in the two other patients with
      FA-Q, was detectable on chromatin, in contrast to XP-F cells, where missense
      mutant protein failed to properly translocate to the nucleus. CONCLUSIONS:
      Patients with FA characteristics and UV sensitivity should be tested for
      mutations in XPF/ERCC4/FANCQ. The missense mutation p.Arg589Trp was previously
      detected in patients diagnosed with Xeroderma pigmentosum or Cockayne syndrome.
      Hence, phenotypic manifestations associated with this XPF/ERCC4/ FANCQ mutation
      are highly variable.

PMID- 29325524
TI  - Posterior decompression and occipitocervical fixation followed by intraoperative
      vertebroplasty for metastatic involvement of the axis.
AB  - BACKGROUND: Metastases to the upper cervical spine were rarely reported in the
      literature. However, metastases to this area may cause spinal instability and
      cord compression, which in turn can result in respiratory failure and
      neurological dysfunction. The present study investigated the efficacy and safety
      of posterior decompression and occipitocervical fixation followed by
      intraoperative vertebroplasty for this disease. METHODS: This was a retrospective
      study that included 10 patients with metastatic involvement of the axis from
      March 2002 to May 2014. All cases presented with occipitocervical pain: 5
      patients with compressive myelopathy and 6 patients with radiculopathy. Japanese
      Orthopedic Association (JOA) scores and Visual Analogue Scale (VAS) were used to
      evaluate the improvement of neurological function and pain intensity,
      respectively. RESULTS: All patients underwent posterior decompression and
      occipitocervical fixation followed by intraoperative vertebroplasty. The VAS
      scores and JOA scores both improved postoperatively, from 8.2 +/- 0.4 to 2.3 +/-
      0.2 and from 10.1 +/- 2.2 to 14.2 +/- 2.9, respectively. Additionally, the
      improvement rate of JOA was 52.4 +/- 1.8%. The mean overall survival was 12.8
      months. The median survival time was 7 months. The 6-month and 12-month survival
      rates were 70% and 40%, respectively. The mean duration of operation was 182 min
      and blood loss was 450 mL. The mean volume of bone cement injected was 4.0 mL.
      The cement extravasation was observed in only 1 patient without clinical
      symptoms. One patient developed tumour recurrence and died 1 month later.
      CONCLUSIONS: Posterior decompression and occipitocervical fixation followed by
      intraoperative vertebroplasty was a safe and valuable palliative method with
      relatively less invasion to treat metastatic involvement of the axis.

PMID- 29325525
TI  - Estimating the scale of chronic hepatitis B virus infection among migrants in
      EU/EEA countries.

PMID- 29325526
TI  - Aortoesophageal fistula and arch pseudoaneurysm after removing of a swallowed
      chicken bone: a case report of one-stage hybrid treatment.
AB  - BACKGROUND: Aortoesophageal fistula (AEF) and arch pseudoaneurysm are rare
      complications induced by a foreign body, and considerable controversy remains
      regarding the appropriate management strategies. We herein report a successful
      one-stage hybrid treatment in a patient with AEF and arch pseudoaneurysm. CASE
      PRESENTATION: The patient, a 40-year-old man, presented to the emergency room
      because of intense retrosternal discomfort for 3 days and hematemesis for 3 h.
      The esophagoscopy and thoracic enhanced computed tomography (CT) showed two
      irregular mural ulcers in the esophagus and a large saccular pseudoaneurysm at
      the aortic isthmus, respectively. The laboratory examinations confirmed no
      widespread inflammation and infection. We have successfully performed a
      successful one-stage hybrid treatment for this patient. Six-month follow-up shows
      the patient is in good condition and the esophagoscopy reveals the two mural
      ulcers had completely healed. CONCLUSION: The treatment decision-making process
      should depend upon the patients' specific situations. Our case suggest the one
      stage hybrid treatment could be an valuable alternative in some selected
      patients.

PMID- 29325527
TI  - Single center experience with laparoscopic adrenalectomy on a large clinical
      series.
AB  - BACKGROUND: Laparoscopic adrenalectomy is considered the gold standard technique
      for the treatment of benign small and medium size adrenal masses (<6 cm), due to
      low morbidity rate, short hospitalization and patient rapid recovery. The aim of
      our study is to analyse the feasibility and efficiency of this surgical approach
      in a broad spectrum of adrenal gland pathologies. METHODS: Pre-operative, intra
      operative and post-operative data from 126 patients undergone laparoscopic
      adrenalectomy between January 2003 and December 2015 were retrospectively
      collected and reviewed. Diagnosis was obtained on the basis of clinical
      examination, laboratory values and imaging techniques. Doxazosin was
      preoperatively administered in case of pheochromocytoma while spironolactone and
      potassium were employed to treat Conn's disease. Laparoscopic adrenalectomies
      were all performed by the same surgeon (CG). First 30 procedures were considered
      as learning curve adrenalectomies. RESULTS: One hundred twenty-six patients were
      included in the study. Functioning tumors were diagnosed in 84 patients, 27
      patients were affected by pheochromocytomas, 29 by Conn's disease, 28 by Cushing
      disease. Surgery mean operative time was 137.33 min (range 100-180) during the
      learning curve adrenalectomies and 96.5 min (range 75-110) in subsequent
      procedures. Mean blood loss was respectively 160.2 ml (range 60-280) and 90.5 ml
      (range 50-200) in the first 30 procedures and the subsequent ones. Only one
      conversion to open surgery occurred. No post-operative major complications were
      observed, while minor complications occurred in 8 patients (0,79%). In 83 out of
      84 functioning neoplasms, laparoscopic adrenalectomy was effective in
      normalization of endocrine profile. CONCLUSIONS: Laparoscopic adrenalectomy is a
      safe and feasible procedure, even for functioning masses and pheochromocytomas. A
      multidisciplinary team including endocrinologists, endocrine surgeons and
      anaesthesiologists, is recommended in the management of adrenal pathology, and
      adrenal surgery should be performed in referral high volume centers. A thirty
      procedures learning curve is recommended to improve surgical outcomes.

PMID- 29325528
TI  - Knowledge, attitudes, and practices regarding cervical cancer and screening among
      women visiting primary health care Centres in Bahrain.
AB  - BACKGROUND: Cervical cancer is one of the most common cancers among women, with
      80% of the cases occurring in developing countries. Cervical cancer is largely
      preventable by effective screening programs. This has not been possible with
      opportunistic screening and its low use in the Kingdom of Bahrain. The objective
      of this study was to explore the knowledge, attitudes, and practices of women
      attending primary care health centres for cervical cancer screening. METHODS:
      This was a cross-sectional study of 300 women attending primary health care
      centres in Bahrain. We used a validated tool comprised of 45 items to collect
      data through face-to-face interviews between December 2015 and February 2016.
      Descriptive data are presented for demographic data, and frequency distributions
      with percentages are presented for each item of the knowledge and attitude
      questionnaire. RESULTS: The mean age +/- SD of the participants was 37.24 +/-
      11.89 years, they were mostly married (221; 73.7%), and had a high school or
      higher education (261; 87%). Over 64% (194 participants) had never heard of a Pap
      smear procedure and only 3.7% (11 participants) had heard about the human
      papillomavirus (HPV) vaccine. Nearly 64% (192 participants) believed that a Pap
      smear was helpful in detecting pre-cancer and cancer of the cervix, and 44.3%
      (133 participants) believed that they should have a Pap smear at least every 3
      years. Regarding the practice, only 40.7% (122 participants) had a Pap smear in
      their lifetime. The majority of participants felt embarrassed when examined by a
      male doctor (250, 83.3%) and few underwent a Pap smear screening if they were
      never married (69, 23.0%). CONCLUSIONS: The participants demonstrated a wide
      range of knowledge and attitudes towards cervical cancer screening. However, the
      majority demonstrated positive attitudes towards the HPV vaccine.

PMID- 29325529
TI  - A multiple imputation method based on weighted quantile regression models for
      longitudinal censored biomarker data with missing values at early visits.
AB  - BACKGROUND: In patient-based studies, biomarker data are often subject to left
      censoring due to the detection limits, or to incomplete sample or data
      collection. In the context of longitudinal regression analysis, inappropriate
      handling of these issues could lead to biased parameter estimates. We developed a
      specific multiple imputation (MI) strategy based on weighted censored quantile
      regression (CQR) that not only accounts for censoring, but also missing data at
      early visits when longitudinal biomarker data are modeled as a covariate.
      METHODS: We assessed through simulation studies the performances of developed
      imputation approach by considering various scenarios of covariance structures of
      longitudinal data and levels of censoring. We also illustrated the application of
      the proposed method to the Prospective Study of Outcomes in Ankylosing
      spondylitis (AS) (PSOAS) data to address the issues of censored or missing C
      reactive protein (CRP) level at early visits for a group of patients. RESULTS:
      Our findings from simulation studies indicated that the proposed method performs
      better than other MI methods by having a higher relative efficiency. We also
      found that our approach is not sensitive to the choice of covariance structure as
      compared to other methods that assume normality of biomarker data. The analysis
      results of PSOAS data from the imputed CRP levels based on our method suggested
      that higher CRP is significantly associated with radiographic damage, while those
      from other methods did not result in a significant association. CONCLUSION: The
      MI based on weighted CQR offers a more valid statistical approach to evaluate a
      biomarker of disease in the presence of both issues with censoring and missing
      data in early visits.

PMID- 29325530
TI  - Knowledge of cervical cancer and HPV vaccine in Bangladeshi women: a population
      based, cross-sectional study.
AB  - BACKGROUND: The objective of this study was to assess the level of knowledge of
      cervical cancer among Bangladeshi women and to assess their willingness to
      receive the human papillomavirus (HPV) vaccine. METHODS: A population-based,
      cross-sectional survey was conducted from July to December 2011 in one urban and
      one rural area of Bangladesh. A total of 2037 ever-married women, aged 14 to 64
      years, were interviewed using a structured questionnaire. Data on socio
      demographic characteristics and knowledge of cervical cancer were collected.
      Willingness to receive the HPV vaccine was assessed. Univariate analyses were
      completed using quantitative data collected. Multivariable logistic regression
      models were developed to identify factors associated with having heard of
      cervical cancer and the HPV vaccine. RESULTS: The majority of study participants
      reported to have heard of cervical cancer (urban: 89.7%, rural 93.4%; P = 0.003).
      The odds of having heard of cervical cancer were significantly higher in urban
      women aged 35-44 years (aOR: 2.92 (1.34-6.33) and rural women aged 25-34 years
      (aOR: 2.90 (1.24-6.73) compared to those aged less than 24 years. Very few women
      reported to have detailed knowledge on risk factors (urban:9.1%, rural: 8.8%) and
      prevention (urban: 6.4%, rural: 4.4%) of cervical cancer. In our sample, one in
      five urban women and one in twenty rural women heard about a vaccine that can
      prevent cervical cancer. Among urban women, secondary education or higher (aOR:
      3.48, 95% CI: 1.67-7.25), age of 20 years and above at marriage (aOR: 2.83, 95%
      CI: 1.61-5.00), and high socioeconomic status (aOR: 2.25, 95% CI: 1.28-3.95) were
      factors associated with having heard of the HPV vaccine. Willingness to receive
      the HPV vaccine among study participants either for themselves (urban: 93.9%,
      rural: 99.4%) or for their daughters (urban: 91.8%, rural: 99.2%) was high.
      CONCLUSIONS: Detailed knowledge of cervical cancer among Bangladeshi women was
      found to be poor. Education on cervical cancer must include information on
      symptoms, risk factors, and preventive methods. Despite poor knowledge, the study
      population was willing to receive the HPV vaccine.

PMID- 29325531
TI  - Costs of potentially inappropriate medication use in residential aged care
      facilities.
AB  - BACKGROUND: The potential harms of some medications may outweigh their potential
      benefits (inappropriate medication use). Despite recommendations to avoid the use
      of potentially inappropriate medications (PIMs) in older adults, the prevalence
      of PIM use is high in different settings including residential aged care.
      However, it remains unclear what the costs of these medications are in this
      setting. The main objective of this study was to determine the costs of PIMs in
      older adults living in residential care. A secondary objective was to examine if
      there was a difference in costs of PIMs in a home-like model of residential care
      compared to an Australian standard model of care. METHODS: Participants included
      541 participants from the Investigation Services Provided in the Residential
      Environment for Dementia (INSPIRED) Study. The INSPIRED study is a cross
      sectional study of 17 residential aged care facilities in Australia. 12 month
      medication costs were determined for the participants and PIMs were identified
      using the 2015 updated Beers Criteria for older adults. RESULTS: Of all of the
      medications dispensed in 1 year, 15.9% were PIMs and 81.4% of the participants
      had been exposed to a PIM. Log-linear models showed exposure to a PIM was
      associated with higher total medication costs (Adjusted beta = 0.307, 95% CI
      0.235 to 0.379, p < 0.001). The mean proportion (+/-SD) of medication costs that
      were spent on PIMs in 1 year was 17.5% (+/-17.8) (AUD$410.89 +/- 479.45 per
      participant exposed to a PIM). The largest PIM costs arose from proton-pump
      inhibitors (34.4%), antipsychotics (21.0%) and benzodiazepines (18.7%). The odds
      of incurring costs from PIMs were 52% lower for those residing in a home-like
      model of care compared to a standard model of care. CONCLUSIONS: The use of PIMs
      for older adults in residential care facilities is high and these medications
      represent a substantial cost which has the potential to be lowered. Further
      research should investigate whether medication reviews in this population could
      lead to potential cost savings and improvement in clinical outcomes. Adopting a
      home-like model of residential care may be associated with reduced prevalence and
      costs of PIMs.

PMID- 29325532
TI  - Mesenteric inflammatory veno-occlusive disease occurring during the course of
      ulcerative colitis: a case report.
AB  - BACKGROUND: Mesenteric inflammatory veno-occlusive disease (MIVOD) is difficult
      to diagnose because of its rarity, nonspecific clinical findings, and frequent
      confusion with other diseases including inflammatory bowel disease. This report
      presents a very rare case of MIVOD that occurred during the course of ulcerative
      colitis (UC). CASE PRESENTATION: A 32-year-old man, who had been diagnosed with
      UC at the age of 29 and was in remission maintained by oral administration of 5
      aminosalicylic acid (5-ASA), showed exacerbation of diarrhea and was admitted to
      the hospital. Since it was deemed an exacerbation of UC, intravenous steroid
      therapy and oral administration of tacrolimus were initiated, but his condition
      continued to worsen. Abdominal computed tomography (CT) was performed and showed
      intraperitoneal free air, leading to a diagnosis of gastrointestinal perforation
      and the performance of emergency surgery (subtotal colectomy and ileostomy).
      Histopathological examination of the resected colon of the patient showed mucosal
      inflammatory findings that were not typical of UC, including multiple organized
      thrombi with recanalization in the veins existing in the submucosal layer to the
      subserosal layer and an increased infiltration of inflammatory cells. These
      findings led to the pathological diagnosis of MIVOD. CONCLUSION: We report a very
      rare case in which MIVOD occurred during the course of UC.

PMID- 29325534
TI  - Increasing Trend in Hospital Deaths Consistent among Older Decedents in Korea: A
      Population-based Study Using Death Registration Database, 2001-2014.
AB  - BACKGROUND: With improvement in hospice palliative care services and long-term
      care, Republic of Korea (hereafter South Korea) has recorded significant changes
      in places of death (e.g., hospital, home), especially among older adults. Over
      the last few decades, the most common places of death in South Korea were
      hospitals. However, Koreans, especially older adults, reportedly prefer to
      receive terminal care and eventually die at home. This study was conducted to
      investigate trends in places of death among older Korean adults and factors
      associated therewith. METHODS: Data were obtained from the Korean Death
      Registration Database maintained by the National Statistical Office. Decedents
      who died after the age of 65 years from 2001 to 2014 were included in the
      analysis. For descriptive analysis, proportions of places of death were analyzed
      and were used to plot graphs for visualizing trends during 13-year period.
      Logistic regression model was used to evaluate factors associated with places of
      death (hospital versus home). RESULTS: Two million three hundred fifty eight
      thousand two hundred eleven older adult decedents were included in final
      analysis. Hospitals were the most common places of death (57.82%), followed by
      homes (32.12%). Dying at social welfare facilities was rare (2.61%). A gradual
      increase in hospital deaths (31.38% in 2001 to 75.30% in 2014) and a subsequent
      decrease in home deaths (60.44% to 15.95% over the same period) were noted.
      Hospital deaths were more likely for younger patients (ORs 1.28, 95% CI 1.27
      1.29), females (ORs 1.28, 95% CI 1.27-1.29), and single/divorced or widowed
      individuals (ORs 1.77, 1.49 and 1.03 respectively). A higher education level and
      living in urban areas were strongly associated with a higher likelihood of dying
      in a hospital. CONCLUSION: Over the study period, there was a consistent
      increasing trend in hospital deaths in South Korea. Trends in place of death and
      factors associated therewith should be more intensely investigated and monitored.
      Resources and facilities should be increased to fulfill end-of-life care
      preferences and the needs of an increasingly older population in South Korea.

PMID- 29325533
TI  - A systematic review of comparisons between protocols or registrations and full
      reports in primary biomedical research.
AB  - BACKGROUND: Prospective study protocols and registrations can play a significant
      role in reducing incomplete or selective reporting of primary biomedical
      research, because they are pre-specified blueprints which are available for the
      evaluation of, and comparison with, full reports. However, inconsistencies
      between protocols or registrations and full reports have been frequently
      documented. In this systematic review, which forms part of our series on the
      state of reporting of primary biomedical, we aimed to survey the existing
      evidence of inconsistencies between protocols or registrations (i.e., what was
      planned to be done and/or what was actually done) and full reports (i.e., what
      was reported in the literature); this was based on findings from systematic
      reviews and surveys in the literature. METHODS: Electronic databases, including
      CINAHL, MEDLINE, Web of Science, and EMBASE, were searched to identify eligible
      surveys and systematic reviews. Our primary outcome was the level of
      inconsistency (expressed as a percentage, with higher percentages indicating
      greater inconsistency) between protocols or registration and full reports. We
      summarized the findings from the included systematic reviews and surveys
      qualitatively. RESULTS: There were 37 studies (33 surveys and 4 systematic
      reviews) included in our analyses. Most studies (n = 36) compared protocols or
      registrations with full reports in clinical trials, while a single survey focused
      on primary studies of clinical trials and observational research. High
      inconsistency levels were found in outcome reporting (ranging from 14% to 100%),
      subgroup reporting (from 12% to 100%), statistical analyses (from 9% to 47%), and
      other measure comparisons. Some factors, such as outcomes with significant
      results, sponsorship, type of outcome and disease speciality were reported to be
      significantly related to inconsistent reporting. CONCLUSIONS: We found that
      inconsistent reporting between protocols or registrations and full reports of
      primary biomedical research is frequent, prevalent and suboptimal. We also
      identified methodological issues such as the need for consensus on measuring
      inconsistency across sources for trial reports, and more studies evaluating
      transparency and reproducibility in reporting all aspects of study design and
      analysis. A joint effort involving authors, journals, sponsors, regulators and
      research ethics committees is required to solve this problem.

PMID- 29325536
TI  - Autonomy and couples' joint decision-making in healthcare.
AB  - BACKGROUND: Respect for autonomy is a key principle in bioethics. However,
      respecting autonomy in practice is complex because most people define themselves
      and make decisions influenced by a complex network of social relationships. The
      extent to which individual autonomy operates for each partner within the context
      of decision-making within marital or similar relationships is largely unexplored.
      This paper explores issues related to decision-making by couples (couples' joint
      decision-making) for health care and the circumstances under which such a
      practice should be respected as compatible with autonomous decision-making.
      DISCUSSION: We discuss the concept of autonomy as it applies to persons and to
      actions, human interdependency and gender roles in decision-making, the dynamics
      and outcomes of couples' joint decision-making, and the ethics of couples' joint
      decision-making. We believe that the extent to which couples' joint decision
      making might be deemed ethically acceptable will vary depending on the context.
      Given that in many traditional marriages the woman is the less dominant partner,
      we consider a spectrum of scenarios of couples' joint decision-making about a
      woman's own health care that move from those that are acceptably autonomous to
      those that are not consistent with respecting the woman's autonomous decision
      making. To the extent that there is evidence that both members of a couple
      understand a decision, intend it, and that neither completely controls the other,
      couples' joint decision-making should be viewed as consistent with the principle
      of respect for the woman's autonomy. At the other end of the spectrum are
      decisions made by the man without the woman's input, representing domination of
      one partner by the other. CONCLUSIONS: We recommend viewing the dynamics of
      couples' joint decision-making as existing on a continuum of degrees of autonomy.
      This continuum-based perspective implies that couples' joint decision-making
      should not be taken at face value but should be assessed against the specific
      cultural, ethnic, and religious backgrounds and personal circumstances of the
      individuals in question.

PMID- 29325535
TI  - Effects of physical activity on colorectal cancer risk among family history and
      body mass index subgroups: a systematic review and meta-analysis.
AB  - BACKGROUND: Physical activity is consistently associated with a reduced risk of
      colorectal cancer in epidemiologic studies. This association among higher risk
      subgroups, such as those with a first-degree family history of colorectal cancer
      or high body mass index remains unclear. METHODS: We searched MEDLINE for studies
      examining physical activity and colorectal cancer risk among higher risk
      subgroups through July 11, 2017. Fifteen and three studies were eligible for
      inclusion for body mass index and first-degree family history of colorectal
      cancer subgroups, respectively. Estimates of the highest to lowest comparison of
      physical activity for each subgroup of risk were pooled using random-effects
      models. RESULTS: The pooled associations of physical activity and colorectal
      cancer risk for those without and with a first-degree family history of
      colorectal cancer were 0.56 (95% confidence interval (CI) = 0.39-0.80) and 0.72
      (95% CI = 0.39-1.32), respectively (pheterogeneity = 0.586). The pooled
      associations of physical activity and colorectal cancer risk for the low and high
      body mass index groups were 0.74 (95% CI = 0.66-0.83) and 0.65 (95% CI = 0.53
      0.79), respectively (pheterogeneity = 0.389). CONCLUSIONS: Overall, a stronger
      relative risk of physical activity on colorectal cancer risk was observed in the
      higher body mass index group, although the difference was not statistically
      significant, suggesting an added benefit of physical activity as a cancer
      prevention strategy in population groups with strong risk factors for colorectal
      cancer. Additional research among these subgroups is warranted.

PMID- 29325538
TI  - Influence of isoflurane exposure in pregnant rats on the learning and memory of
      offsprings.
AB  - BACKGROUND: About 2% of pregnant women receive non-obstetric surgery under
      general anesthesia each year. During pregnancy, general anesthetics may affect
      brain development of the fetus. This study aimed to investigate safe dosage range
      of isoflurane. METHODS: Forty-eight SpragueDawley (SD) pregnant rats were
      randomly divided into 3 groups and inhaled 1.3% isoflurane (the Iso1 group), 2.0%
      isoflurane (the Iso2 group) and 50% O2 alone (the control group) for 3 h,
      respectively. Their offsprings were subjected to Morris water maze at day 28 and
      day 90 after birth to evaluate learning and memory. The expression of cAMP
      response element binding protein (CREB) and phosphorylated cAMP-response element
      binding protein (p-CREB) was detected in the hippocampus dentate gyrus. RESULTS:
      Less offsprings of Iso2 group were able to cross the platform than that of the
      control group (P < 0.05). Accordingly, the Iso2 offsprings expressed p-CREB
      mainly in the subgranular zone in contrast to the whole granular cell layer of
      hippocampus dentate gyrus as detected in the Iso1 and control offsprings; the
      expression level of pCREB was also lower in the Iso2 than Iso1 or control
      offsprings (P < 0.05). CONCLUSION: Inhalation of isoflurane at 1.3% during
      pregnancy has no significant influence on learning and memory of the offspring;
      exposure to isoflurane at 2.0% causes damage to spatial memory associated with
      inhibition of CREB phosphorylation in the granular cell layer of hippocampus
      dentate gyrus.

PMID- 29325537
TI  - Factors associated with the prevalence of back pain and work absence in shipyard
      workers.
AB  - BACKGROUND: We conducted a questionnaire survey of shipyard workers to identify
      difficulties experienced due to orthopedic or musculoskeletal disorders. METHODS:
      The subjects were 375 workers (male, 361; female, 14) who worked for a single
      shipbuilding company. Questionnaire items covered the working environment,
      including work environment, working posture, and the weight of objects that the
      subject dealt with, as well as physical and lifestyle characteristics, namely
      smoking habits, drinking habits, sleeping hours, medications, exercise habits,
      and any weight gain of 20 kg or more since the age of 20. Subjects were also
      asked to indicate if they regularly experienced any of 17 listed difficulties in
      their daily lives, and to use an illustration of the human body to mark any body
      parts that were painful or hard to move. RESULTS: The mean age was 41.8 years (19
      73 years). The lower and/or upper back was the most frequent site of pain
      (46.5%), followed by the shoulders (11.4%), knees (9.6%), and neck (5.3%).
      Maintaining a half-sitting posture was the most problematic activity of daily
      living. Back pain was less frequent in subjects who exercised regularly, and more
      common in those who worked with heavy loads or in narrow spaces. A multinomial
      logistic regression analysis showed that absence from work was more common in
      subjects with back pain who had gained weight since their youth, who smoked, who
      used fire while welding metal, or who worked in a lying posture. While 35.4% of
      subjects had experienced absence from work due to musculoskeletal pain, only 5.1%
      were permitted by their employer to alter their work content or reduce their
      workload. CONCLUSIONS: These results indicate that a large number of shipyard
      workers have difficulties in their work and daily life activities due to back
      pain. To prevent worsening of pain and to reduce work absence, it is important to
      provide appropriate training to minimize the risk factors for back pain that were
      identified in this study.

PMID- 29325540
TI  - Correction to: Metalloproteases meprin-alpha (MEP1A) is a prognostic biomarker
      and promotes proliferation and invasion of colorectal cancer.
AB  - CORRECTION: After publication of the original article [1] the authors found that
      the figure contained an incorrect version of Fig. 3a. This does not affect the
      results and conclusions of the article.

PMID- 29325539
TI  - Chinese Cervicocephalic artery dissection study (CCADS): rationale and protocol
      for a multicenter prospective cohort study.
AB  - BACKGROUND: Cervicocephalic artery dissection (CAD) is an important etiology of
      stroke in the youth. Findings from recent studies suggest it a "group of disease
      entities" with different underlying etiologies, presentations and prognosis,
      necessitating an integral study including various types of CAD to get a better
      understanding of this disease. In addition, Chinese patients with CAD are likely
      to carry different features from their western counterparts, which remains
      uncertain yet. Chinese Cervicocephalic Artery Dissection Study (CCADS) therefore
      aims at exploring the epidemiology, risk factors, clinical/radiological features,
      diagnosis and prognosis of CAD in Chinese patients. METHODS/DESIGN: CCADS is a
      multicenter prospective cohort study enrolling patients age >= 18 years with
      recent (<14 days after onset) CAD. Baseline clinical data, laboratory tests and
      imaging studies are performed within 3 days after admission, and follow-ups will
      be conducted through face-to-face interviews at discharge, 3 months, 6 months and
      12 months after admission, when the modified Rankin Scale (mRS), cerebrovascular
      events, medication compliance, CAD evolution and so on are evaluated. Additional
      blood samples will also be collected at baseline, 3 and 12 months follow-up. The
      primary outcome is radiographic evolution of CAD; secondary outcomes include
      cerebrovascular events, major bleeding complications, all-cause mortality and
      functional independence. DISCUSSION: Through the integration of information on
      epidemiology, risk factors, clinical/radiological features and prognosis of
      various types of CAD in Chinese population, combined with the application of
      advanced imaging techniques, collection of potential blood biomarkers, and
      assessment of novel treatment strategies. CCADS will provide thorough information
      on CAD - the major cause of stroke in the youth, and play a role in prevention
      and treatment determination in the future.

PMID- 29325541
TI  - Interprofessional collaboration in nursing homes (interprof): development and
      piloting of measures to improve interprofessional collaboration and
      communication: a qualitative multicentre study.
AB  - BACKGROUND: Given both the increase of nursing home residents forecast and
      challenges of current interprofessional interactions, we developed and tested
      measures to improve collaboration and communication between nurses and general
      practitioners (GPs) in this setting. Our multicentre study has been funded by the
      German Federal Ministry of Education and Research (FK 01GY1124). METHODS: The
      measures were developed iteratively in a continuous process, which is the focus
      of this article. In part 1 "exploration of the situation", interviews were
      conducted with GPs, nurses, nursing home residents and their relatives focusing
      on interprofessional interactions and medical care. They were analysed
      qualitatively. Based on these results, in part 2 "development of measures to
      improve collaboration", ideas for improvement were developed in nine focus groups
      with GPs and nurses. These ideas were revisited in a final expert workshop. We
      analysed the focus groups and expert workshop using mind mapping methods, and
      finally drew up the compilation of measures. In an exploratory pilot study "study
      part 3" four nursing homes chose the measures they wanted to adopt. These were
      tested for three months. Feasibility and acceptance of the measures were
      evaluated via guideline interviews with the stakeholders which were analysed by
      content analyses. RESULTS: Six measures were generated: meetings to establish
      common goals, main contact person, standardised pro re nata medication,
      introduction of name badges, improved availability of nurse/GP and standardised
      scheduling/ procedure for nursing home visits. In the pilot study, the measures
      were implemented in four nursing homes. GPs and nurses reviewed five measures as
      feasible and acceptable, only the designation of a "main contact person" was not
      considered as an improvement. CONCLUSIONS: Six measures to improve collaboration
      and communication could be compiled in a multistep qualitative process respecting
      the perspectives of involved stakeholders. Five of the six measures were
      positively assessed in an exploratory pilot study. They could easily be
      transferred into the daily routine of other nursing homes, as no special models
      have to exist in advance. Impact of the measures on patient oriented outcomes
      should be examined in further research. TRIAL REGISTRATION: Not applicable.

PMID- 29325542
TI  - Visceral adipose tissue and carotid intima-media thickness in HIV-infected
      patients undergoing cART: a prospective cohort study.
AB  - BACKGROUND: Combined antiretroviral therapy (cART) in HIV-infected patients has
      been associated with lipodystrophy, metabolic abnormalities, and an increased
      risk of cardiovascular disease. Ultrasound measures of carotid artery intima
      media thickness (cIMT) have been used as a valid measure of subclinical
      atherosclerosis and as a tool to predict the risk of cardiovascular events. Our
      aim was to evaluate the progression of cIMT in HIV-infected patients subjected to
      cART, with and without lipodystrophy, over a one-year period. METHODS: We
      performed a one-year prospective cohort study to compare changes in cIMT,
      metabolic and inflammation markers in HIV-infected patients undergoing cART. Body
      composition was assessed by dual-energy X-ray absorptiometry (DXA) and abdominal
      computed tomography (CT). Levels of blood pressure, lipids and inflammatory
      markers were evaluated, as well as ultrasound measures of cIMT. Lipodystrophy
      defined by Fat Mass Ratio (L-FMR) is measured as the ratio of the percentage of
      trunk fat mass to the percentage of lower limb fat mass by DXA. Categorical
      variables were compared, using the chi-square or Fisher's exact test. Wilcoxon
      ranks tests and the McNemar chi-square tests were used to compare results of
      selected variables, from the first to the second year of evaluation. Means of
      cIMT, adjusted for age, glucose, triglycerides levels, systolic blood pressure
      (SBP), and waist to hip ratio were calculated, using generalised linear models
      for repeated measures. RESULTS: L-FMR was present in 44.3% of patients, and the
      mean of cIMT increased significantly in this group [0.82 (0.26) vs 0.92 (0.33); p
      = 0.037], as well as in patients without lipodystrophy [0.73 (0.20) vs 0.84
      (0.30); p = 0.012]. In the overall sample, the progression of cIMT was
      statistically significant after the adjustment for age, glucose, triglycerides,
      and SBP, but the significance of the progression ceased after the adjustment for
      waist/hip ratio [0.770 (0.737-0.803) vs 0.874 (0.815-0.933); p = 0.514].
      CONCLUSIONS: Carotid IMT progressed significantly in both groups of this HIV
      infected cohort, however no association between the progression of cIMT and the
      presence of lipodystrophy defined by FMR was found. Visceral adipose tissue had
      an impact on the increment of cIMT, both in patients with, and without
      lipodystrophy defined by FMR.

PMID- 29325543
TI  - Persistent mammalian orthoreovirus, coxsackievirus and adenovirus co-infection in
      a child with a primary immunodeficiency detected by metagenomic sequencing: a
      case report.
AB  - BACKGROUND: We report a rare case of Mammalian orthoreovirus (MRV) infection in a
      child with a primary immunodeficiency (PID). Infections with Mammalian
      orthoreovirus are very rare and probably of zoonotic origin. Only a few cases
      have been described so far, including one with similar pathogenesis as in our
      case. CASE PRESENTATION: The patient, age 11, presented with flu-like symptoms
      and persistent severe diarrhea. Enterovirus has been detected over several
      months, however, exact typing of a positive cell culture remained inconclusive.
      Unbiased metagenomic sequencing then detected MRV in stool samples from several
      time points. The sequencing approach further revealed co-infection with a
      recombinant Coxsackievirus and Adenovirus. MRV-specific antibodies detected by
      immunofluorescence proved that the patient seroconverted. CONCLUSION: This case
      highlights the potential of unbiased metagenomic sequencing in supplementing
      routine diagnostic methods, especially in situations of chronic infection with
      multiple viruses as seen here in an immunocompromised host. The origin,
      transmission routes and implications of MRV infection in humans merit further
      investigation.

PMID- 29325544
TI  - Prevalence and associated factors of wheezing illnesses of children aged three to
      five years living in under-served settlements of the Colombo Municipal Council in
      Sri Lanka: a cross-sectional study.
AB  - BACKGROUND: A rising trend in Sri Lanka for asthma and wheezing illness is
      observed with higher morbidity in younger children and a paucity of related
      research. 'Under-served settlements' (USS) of Colombo Municipal Council (CMC)
      have poor living environments conducive to childhood wheezing. The objective was
      to describe the prevalence and associated factors of wheezing illnesses of three
      to five year old children living in low-income settlements in CMC. METHODS: A
      cross-sectional study was conducted on 460 three to five year old children and
      their caregivers using cluster sampling among residents of two randomly selected
      USSs of CMC. An interviewer-administered questionnaire, observation checklist and
      data extraction form were used in data collection. A physician's diagnosis of
      wheezing/whistling of the chest in their lifetime and a physician's diagnosis of
      wheezing/whistling within the past twelve months were considered as 'ever
      wheezing illness' and 'current-wheezing illness' respectively. RESULTS: Mean age
      was 3.98 years (SD = +/-0.64 years). A majority were males (51.3%) and Tamils
      (39.8%). Prevalence of 'ever wheezing illness' and 'current wheezing illness'
      were 38% (95% confidence interval (CI); 33.6%-42.5%) and 21.3% (95%CI; 17.6%
      25.0%), respectively. Maternal (p < 0.001) and paternal (p < 0.001) histories of
      wheezing, playing with soft toys in the sleeping area (p = 0.004), place of
      cooking combined with the living area (p = 0.03), unsatisfactory ventilation in
      the sleeping area (p < 0.001) were found to be significantly associated with
      increased 'current wheezing' through multivariate analysis in this study. Use of
      formula milk before six months of age (p = 0.014) was found to be protective
      through multivariate analysis. CONCLUSIONS: The magnitude of wheezing illnesses
      among three to five year old children residing in urban low-income settlements
      was found to be high. Children with a history of maternal and/or paternal
      wheezing should be targeted for early interventions to prevent wheezing
      illnesses. Interventions to avoid exacerbations should focus on the indoor
      environmental factors that were found to be associated with wheezing illnesses.

PMID- 29325545
TI  - Phthiocerol dimycocerosates promote access to the cytosol and intracellular
      burden of Mycobacterium tuberculosis in lymphatic endothelial cells.
AB  - BACKGROUND: Phthiocerol dimycocerosates (PDIM), glycolipids found on the outer
      surface of virulent members of the Mycobacterium tuberculosis (Mtb) complex, are
      a major contributing factor to the pathogenesis of Mtb. Myelocytic cells, such as
      macrophages and dendritic cells, are the primary hosts for Mtb after infection
      and previous studies have shown multiple roles for PDIM in supporting Mtb in
      these cells. However, Mtb can infect other cell types. We previously showed that
      Mtb efficiently replicates in human lymphatic endothelial cells (hLECs) and that
      the hLEC cytosol acts as a reservoir for Mtb in humans. Here, we examined the
      role of PDIM in Mtb translocation to the cytosol in hLECs. RESULTS: Analysis of a
      Mtb mutant unable to produce PDIM showed less co-localisation of bacteria with
      the membrane damage marker Galectin-8 (Gal8), indicating that PDIM strongly
      contribute to phagosomal membrane damage. Lack of this Mtb lipid also leads to a
      reduction in the proportion of Mtb co-localising with markers of macroautophagic
      removal of intracellular bacteria (xenophagy) such as ubiquitin, p62 and NDP52.
      hLEC imaging with transmission electron microscopy shows that Mtb mutants lacking
      PDIM are much less frequently localised in the cytosol, leading to a lower
      intracellular burden. CONCLUSIONS: PDIM is needed for the disruption of the
      phagosome membrane in hLEC, helping Mtb avoid the hydrolytic phagolysosomal
      milieu. It facilitates the translocation of Mtb into the cytosol, and the
      decreased intracellular burden of Mtb lacking PDIM indicates that the cytosol is
      the preferred replicative niche for Mtb in these cells. We hypothesise that
      pharmacological targeting of PDIM synthesis in Mtb would reduce the formation of
      a lymphatic reservoir of Mtb in humans.

PMID- 29325546
TI  - Development and evaluation of a measure of patient-reported symptoms of
      Blepharitis.
AB  - BACKGROUND: Blepharitis is an ocular surface disease and chronic ophthalmic
      condition. This paper reports on the development of psychometric evaluation of a
      patient-reported measure of blepharitis symptoms. METHODS: Self-reports of 13
      blepharitis symptoms collected in a Phase 3 multi-site, randomized, double
      masked, 4-arm parallel group, clinical trial of 907 individuals with blepharitis
      (mean age = 62, range: 19-93; 57% female) were analyzed. Symptoms asked about
      were: eyes that itch; eyes that burn; eyelids feel heavy or puffy; feel like
      something is in your eye; dry eyes; gritty eyes; irritated eyes; eyes that tear
      or water; crusty eyes; flaking from your eyelids; eyelids that are stuck
      together; red eyes or eyelids; and debris like pieces of skin or dandruff in your
      eyes. RESULTS: Categorical factor analyses provided support for two multi-item
      symptom scales: Irritation (9 items, alpha = 0.88) and Debris (4 items, alpha =
      0.85). Spearman-rank order correlations of the Irritation and Debris scales with
      the Ocular Surface Disease total score were 0.63 and 0.41, respectively (p's <
      0.001). Rank-order correlations between ratings of clinicians and self-reports of
      puffy eyes (r = 0.07, p < .05), red eyes (r = 0.12, p < .001), debris (r = 0.03,
      p > 0.05), and irritation (r = 0.47, p < .001). CONCLUSIONS: This study provides
      support for the psychometric properties and construct validity of the Irritation
      and Debris scales for assessing symptoms of blepharitis. The associations between
      the self-reports and clinician ratings of 4 symptoms indicate substantial unique
      information in the new self-reported symptom items. TRIAL REGISTRATION: The trial
      was registered at ClinicalTrials.gov under the registry number NCT01408082 .

PMID- 29325547
TI  - Paracrine and epigenetic control of CAF-induced metastasis: the role of HOTAIR
      stimulated by TGF-beta1 secretion.
AB  - BACKGROUND: The communication between carcinoma associated fibroblasts (CAFs) and
      cancer cells facilitate tumor metastasis. In this study, we further underlying
      the epigenetic mechanisms of CAFs feed the cancer cells and the molecular
      mediators involved in these processes. METHODS: MCF-7 and MDA-MB-231 cells were
      treated with CAFs culture conditioned medium, respectively. Cytokine antibody
      array, enzyme-linked immunosorbent assay, western blotting and immunofluorescence
      were used to identify the key chemokines. Chromatin immunoprecipitation and
      luciferase reporter assay were performed to explore the transactivation of target
      LncRNA by CAFs. A series of in vitro assays was performed with RNAi-mediated
      knockdown to elucidate the function of LncRNA. An orthotopic mouse model of MDA
      MB-231 was conducted to confirm the mechanism in vivo. RESULTS: Here we reported
      that TGF-beta1 was top one highest level of cytokine secreted by CAFs as revealed
      by cytokine antibody array. Paracrine TGF-beta1 was essential for CAFs induced
      EMT and metastasis in breast cancer cells, which is a crucial mediator of the
      interaction between stromal and cancer cells. CAF-CM significantly enhanced the
      HOTAIR expression to promote EMT, whereas treatment with small-molecule
      inhibitors of TGF-beta1 attenuated the activation of HOTAIR. Most importantly,
      SMAD2/3/4 directly bound the promoter site of HOTAIR, located between nucleotides
      -386 and -398, -440 and -452, suggesting that HOTAIR was a directly
      transcriptional target of SMAD2/3/4. Additionally, CAFs mediated EMT by targeting
      CDK5 signaling through H3K27 tri-methylation. Depletion of HOTAIR inhibited CAFs
      induced tumor growth and lung metastasis in MDA-MB-231 orthotopic animal model.
      CONCLUSIONS: Our findings demonstrated that CAFs promoted the metastatic activity
      of breast cancer cells by activating the transcription of HOTAIR via TGF-beta1
      secretion, supporting the pursuit of the TGF-beta1/HOTAIR axis as a target in
      breast cancer treatment.

PMID- 29325548
TI  - A pre-post study testing a lung cancer screening decision aid in primary care.
AB  - BACKGROUND: The United States Preventive Services Task Force (USPSTF) issued
      recommendations for older, heavy lifetime smokers to complete annual low-dose
      computed tomography (LDCT) scans of the chest as screening for lung cancer. The
      USPSTF recommends and the Centers for Medicare and Medicaid Services require
      shared decision making using a decision aid for lung cancer screening with annual
      LDCT. Little is known about how decision aids affect screening knowledge,
      preferences, and behavior. Thus, we tested a lung cancer screening decision aid
      video in screening-eligible primary care patients. METHODS: We conducted a single
      group study with surveys before and after decision aid viewing and medical record
      review at 3 months. Participants were active patients of a large US academic
      primary care practice who were current or former smokers, ages 55-80 years, and
      eligible for screening based on current screening guidelines. Outcomes assessed
      pre-post decision aid viewing were screening-related knowledge score (9 items
      about screening-related harms of false positives and overdiagnosis, likelihood of
      benefit; score range = 0-9) and preference (preferred screening vs. not).
      Screening behavior measures, assessed via chart review, included provider visits,
      screening discussion, LDCT ordering, and LDCT completion within 3 months.
      RESULTS: Among 50 participants, knowledge increased from pre- to post-decision
      aid viewing (mean = 2.6 vs. 5.5, difference = 2.8; 95% CI 2.1, 3.6, p < 0.001).
      Preferences across the overall sample remained similar such that 54% preferred
      screening at baseline and 50% after viewing; however, 28% of participants changed
      their preference (to or away from screening) from baseline to after viewing. We
      assessed screening behavior for 36 participants who had a primary care visit
      during the 3-month period following enrollment. Eighteen of 36 preferred
      screening after decision aid viewing. Of these 18, 10 discussed screening, 8 had
      a test ordered, and 6 completed LDCT. Among the 18 who preferred no screening, 7
      discussed screening, 5 had a test ordered, and 4 completed LDCT. CONCLUSIONS: In
      primary care patients, a lung cancer screening decision aid improved knowledge
      regarding screening-related benefits and harms. Screening preferences and
      behavior were heterogeneous. TRIAL REGISTRATION: This study is registered at
      www.clinicaltrials.gov . NCT03077230 (registered retrospectively,November 22,
      2016).

PMID- 29325549
TI  - Does exposure to interparental violence increase women's risk of intimate partner
      violence? Evidence from Nigeria demographic and health survey.
AB  - BACKGROUND: Exposure to interparental violence (EIPV) has been identified as a
      risk factor for intimate partner violence (IPV). However, studies in Nigeria have
      rarely and specifically examined exposure to interparental violence as a
      predictor of IPV. The objective of the study was to examine the relationship
      between exposure to interparental violence and women's experience of intimate
      partner violence. METHODS: The 2013 Nigeria Demographic and Health Survey (NDHS)
      women recode dataset was analysed. The weighted sample size was 19,925 women aged
      15-49 years. The outcome variable was women's experience of at least one type of
      IPV measured by combining partner physical, sexual and emotional violence
      experienced by the surveyed women. The main explanatory variable was exposure to
      interparental violence measured by response to question on whether a woman
      witnessed her father ever beat her mother. Individual/relationship and community
      characteristics were selected for statistical control in the study. The
      multilevel mixed-effect regression was applied in three models using Stata
      version 12. Model 1 was based solely on interparental violence, while
      individual/relationship factors were included in Model 2. In Model 3, all
      research variables were included. RESULTS: The study revealed that less than one
      tenth of the women witnessed interparental violence, and women exposed to
      interparental violence compared with non exposed women had higher prevalence of
      all forms of IPV. In Model 1, women exposed to interparental violence were more
      than five times as likely as non exposed women to experience IPV (OR = 5.356; CI:
      3.371-8.509). In Model 2, women exposed to interparental violence were nearly
      five times as likely as non exposed women to experience IPV (OR = 4.489; CI:
      3.047-6.607). In Model 3, women exposed to interparental violence were four times
      as likely as non exposed women to experience IPV (OR = 4.018; CI: 2.626-6.147).
      CONCLUSION: The study provided additional evidence that exposure to interparental
      violence increase women's risk of IPV in Nigeria. Reducing future prevalence of
      intimate partner violence may require social and behaviour change communication
      (SBCC) that not only change perception of children who witnessed interparental
      violence, but also help them to overcome intergenerational effects of
      interparental aggression.

PMID- 29325550
TI  - Acute-onset high-morbidity primary photosensitisation in sheep associated with
      consumption of the Casbah and Mauro cultivars of the pasture legume Biserrula.
AB  - BACKGROUND: Primary photosensitisation (PS) subsequent to ingestion of the
      pasture legume Biserrula pelecinus L. (biserrula) has recently been confirmed in
      grazing livestock. Given the potential utility of this pasture species in
      challenging climates, a grazing trial was undertaken to examine if both varieties
      'Casbah' and 'Mauro' were able to cause photosensitisation in livestock, and if
      this could be mitigated by grazing in winter, or in combination with other common
      pasture species. RESULTS: A controlled grazing trial was undertaken in winter in
      Australia with plots containing a dominant pasture of Biserrula pelecinus L. cv.
      'Casbah' or 'Mauro', or mixed biserrula/perennial ryegrass populations. A
      photosensitisation grading system was established. 167 prime meat ewe lambs were
      introduced to the plots and monitored twice daily. Mild clinical signs were
      observed at 72 h on pasture. All animals were removed from biserrula dominant
      stands at this point. Four animals grazing 'Casbah' dominant pasture rapidly
      proceeded to severe photosensitisation in the following 12 h. Animals remaining
      on mixed biserrula/ryegrass stands did not exhibit severe PS but showed an 89%
      incidence of mild to moderate photosensitisation over the following 14 days.
      Animals on mixed lucerne showed significantly lower PS score than animals grazing
      biserrula varieties of any composition. The trial was halted at 14 days as only
      plots with low biserrula proportion still contained unaffected animals. Necropsy
      revealed severe multifocal erythematous ulcerations and alopecia of the ear
      pinnae, severe bilateral periorbital and conjunctival oedema and variably severe
      subcutaneous facial oedema. No evidence of hepatopathy was present. A diagnosis
      of acute unseasonal primary photosensitisation caused by biserrula ingestion with
      no other underlying pathology was confirmed. CONCLUSIONS: We report an unseasonal
      outbreak of acute photosensitisation in sheep grazing Biserrula pelecinus L
      cvs.'Casbah' and 'Mauro' with exceedingly high morbidity. A grading system is
      also proposed as a tool for objective and consistent clinical appraisal of future
      PS outbreaks. This finding expands our definition of seasonal and temporal risk
      periods for biserrula photosensitisation, and is the first to identify that both
      commercial cultivars of biserrula can cause primary photosensitisation in sheep.

PMID- 29325551
TI  - Relationship between cardiac microvascular dysfunction measured with 82Rubidium
      PET and albuminuria in patients with diabetes mellitus.
AB  - BACKGROUND: Albuminuria is of one the strongest predictors of cardiovascular
      disease (CVD) in diabetes. Diabetes is associated with cardiac microvascular
      dysfunction (CMD), a powerful, independent prognostic factor for cardiac
      mortality. The aim of this study was to evaluate the relationship between CMD and
      microvascular complications in patients without known CVD. METHODS: In this
      monocentric study, myocardial flow reserve (MFR) was measured with cardiac
      82Rubidium positron emission tomography (Rb-PET) in 311 patients referred to
      nuclear medicine department of Bichat University Hospital for screening of
      coronary artery disease from 2012 to 2014. Patients with hemodynamically relevant
      stenosis on coronary angiography or myocardial ischemia on Rb-PET were excluded.
      Among patients with diabetes, MFR values were compared according to the presence
      of retinopathy and albuminuria. RESULTS: Overall, 175 patients (118 with type 2
      diabetes) were included. MFR was significantly lower in patients with diabetes
      compared with those without diabetes (2.6 +/- 1.1 vs. 3.3 +/- 1.7; p < 0.005). In
      patients with diabetes, MFR decreased progressively in relation to albumin
      urinary excretion (normoalbuminuria: 2.9 +/- 1.1, microalbuminuria: 2.3 +/- 1.0,
      macroalbuminuria: 1.8 +/- 0.7; p < 0.0001). MFR was not significantly different
      in patients with vs. without retinopathy (2.4 +/- 1.0 vs. 2.7 +/- 1.1, p = 0.07).
      Microalbuminuria and macroalbuminuria remained strongly associated with impaired
      MFR after multiple adjustments [odds ratio 2.6 (95% CI 1.1-8.4) and 5.3 (95% CI
      1.2-44.7), respectively]. This association was confirmed when analyses were
      restricted to patients with low levels of coronary calcifications on computed
      tomography. CONCLUSIONS: Impaired MFR was more frequent in patients with diabetes
      and was strongly associated with the degree of albuminuria suggesting that CMD
      and albuminuria might share common mechanisms.

PMID- 29325552
TI  - Health care access for rural youth on equal terms? A mixed methods study protocol
      in northern Sweden.
AB  - BACKGROUND: The purpose of this paper is to propose a protocol for researching
      the impact of rural youth health service strategies on health care access. There
      has been no published comprehensive assessment of the effectiveness of youth
      health strategies in rural areas, and there is no clearly articulated model of
      how such assessments might be conducted. The protocol described here aims to
      gather information to; i) Assess rural youth access to health care according to
      their needs, ii) Identify and understand the strategies developed in rural areas
      to promote youth access to health care, and iii) Propose actions for further
      improvement. The protocol is described with particular reference to research
      being undertaken in the four northernmost counties of Sweden, which contain a
      widely dispersed and diverse youth population. METHODS: The protocol proposes
      qualitative and quantitative methodologies sequentially in four phases. First, to
      map youth access to health care according to their health care needs, including
      assessing horizontal equity (equal use of health care for equivalent health
      needs,) and vertical equity (people with greater health needs should receive more
      health care than those with lesser needs). Second, a multiple case study design
      investigates strategies developed across the region (youth clinics, internet
      applications, public health programs) to improve youth access to health care.
      Third, qualitative comparative analysis of the 24 rural municipalities in the
      region identifies the best combination of conditions leading to high youth access
      to health care. Fourth, a concept mapping study involving rural stakeholders,
      care providers and youth provides recommended actions to improve rural youth
      access to health care. DISCUSSION: The implementation of this research protocol
      will contribute to 1) generating knowledge that could contribute to strengthening
      rural youth access to health care, as well as to 2) advancing the application of
      mixed methods to explore access to health care.

PMID- 29325554
TI  - An analysis of the global pharmacy workforce capacity trends from 2006 to 2012.
AB  - BACKGROUND: Human resources for health are at a critical low. The World Health
      Organization estimates that the current shortage of health workers, including
      pharmacists, is in excess of 7.2 million worldwide and that, by 2035, the
      shortage will reach 12.9 million. Pharmacists, in particular, are lacking in the
      workforce in many countries. The International Pharmaceutical Federation (FIP)
      and academic partners have conducted periodic global pharmacy workforce surveys
      in 2006, 2009 and 2012 which have monitored and reported on the status of the
      pharmacy workforce at the country and territory levels. This current analysis is
      a synthesis of workforce capacity data from these date points to provide an
      overview of the global trends and changes to pharmacy workforce capacity over
      this time period. METHODS: The methodology proceeded with accessing workforce
      capacity data collated in 2006, 2009 and 2012 held on file at the FIP
      Collaborating Centre. This data had previously been validated and made available
      to WHO Human Resources for Health. The data focused (due to limitations from 2006
      databank) on pharmacist workforce capacity. Countries and territories were
      identified that had data available across at least two of the three time points
      (2006, 2009 and 2012). Missing time-point data for some countries (data gaps)
      were subject, where possible, to literature and online data searching to capture
      possible missing data. Country-level capacity data were plotted against time to
      identify trends coupled with comparative analysis of the trends. RESULTS: The
      countries and territories identified as having valid data for each of the time
      points 2006, 2009 and 2012 were present in all WHO regions, with Europe having
      the most countries with data available and South East Asia the fewest. All WHO
      regions have experienced an increase in the density of pharmacists (measured as
      number of pharmacists per 10 000 population) over the period 2006-2012. However,
      some countries show a reduction in the density of pharmacists. African countries
      show large relative increases in acceleration of capacity building but remain
      significantly behind in terms of absolute capacity per capita. South East Asian
      and Middle Eastern countries also show large proportional changes in pharmacist
      workforce. CONCLUSION: The global trend is an increase in workforce across all
      nations and regions, and this is a move in the right direction towards improved
      access to, and availability of, pharmaceutical expertise. However, there is still
      much to be done, with some regions and low-income countries still displaying a
      disproportionately low number of pharmacists on small overall capacity for
      delivering pharmacy services.

PMID- 29325553
TI  - Sitagliptin improved glucose assimilation in detriment of fatty-acid utilization
      in experimental type-II diabetes: role of GLP-1 isoforms in Glut4 receptor
      trafficking.
AB  - BACKGROUND: The distribution of glucose and fatty-acid transporters in the heart
      is crucial for energy consecution and myocardial function. In this sense, the
      glucagon-like peptide-1 (GLP-1) enhancer, sitagliptin, improves glucose
      homeostasis but it could also trigger direct cardioprotective actions, including
      regulation of energy substrate utilization. METHODS: Type-II diabetic GK (Goto
      Kakizaki), sitagliptin-treated GK (10 mg/kg/day) and wistar rats (n = 10, each)
      underwent echocardiographic evaluation, and positron emission tomography scanning
      for [18F]-2-fluoro-2-deoxy-D-glucose (18FDG). Hearts and plasma were isolated for
      biochemical approaches. Cultured cardiomyocytes were examined for receptor
      distribution after incretin stimulation in high fatty acid or high glucose media.
      RESULTS: Untreated GK rats exhibited hyperglycemia, hyperlipidemia, insulin
      resistance, and plasma GLP-1 reduction. Moreover, GK myocardium decreased 18FDG
      assimilation and diastolic dysfunction. However, sitagliptin improved
      hyperglycemia, insulin resistance, and GLP-1 levels, and additionally, enhanced
      18FDG uptake and diastolic function. Sitagliptin also stimulated the sarcolemmal
      translocation of the glucose transporter-4 (Glut4), in detriment of the fatty
      acyl translocase (FAT)/CD36. In fact, Glut4 mRNA expression and sarcolemmal
      translocation were also increased after GLP-1 stimulation in high-fatty acid
      incubated cardiomyocytes. PI3K/Akt and AMPKalpha were involved in this response.
      Intriguingly, the GLP-1 degradation metabolite, GLP-1(9-36), showed similar
      effects. CONCLUSIONS: Besides of its anti-hyperglycemic effect, sitagliptin
      enhanced GLP-1 may ameliorate diastolic dysfunction in type-II diabetes by
      shifting fatty acid to glucose utilization in the cardiomyocyte, and thus,
      improving cardiac efficiency and reducing lipolysis.

PMID- 29325555
TI  - The readiness of hospital pharmacists in Kuwait to practise evidence-based
      medicine: a cross-sectional study.
AB  - BACKGROUND: The evolving role of pharmacists in providing pharmaceutical care, as
      part of the healthcare team, challenges them to acquire up-to-date knowledge of
      medicines to make the best clinical decisions. The volume of medical literature
      is on the increase, and it is important to utilise these resources to optimise
      patients' therapeutic outcomes. This study aimed at assessing the readiness of
      government hospital pharmacists in practising evidence-based medicine (EBM) in
      Kuwait in regards to their attitude, knowledge and skills, as well as the
      perceived barriers and facilitators. METHODS: This descriptive cross-sectional
      study used pre-tested self-reported questionnaires to collect information from
      pharmacists working at government hospitals in Kuwait. In addition, one-to-one,
      face-to-face semi-structured interviews were conducted with the chief pharmacists
      of all health regions in Kuwait to discuss and identify the barriers and
      facilitators of implementing EBM in the hospitals. Quantitative and qualitative
      analytical measures were undertaken for the data acquired from the questionnaires
      and interviews, respectively. RESULTS: A total of 176 pharmacists (of 445)
      working in secondary and tertiary government hospitals in Kuwait agreed to take
      part in the study, giving a response rate of 40%. Over half of the study sample
      (n = 94, 53.4%) had good confidence in performing online database searches.
      Approximately 50% of the pharmacists were familiar with searching the Internet
      for medical resources, asking answerable clinical questions and retrieving
      research evidence. However, 67% of the pharmacists (n = 118) were neither able to
      apply research evidence to patient care nor capable of identifying knowledge gaps
      in practice. Barriers to EBM practice were identified, which included limited
      access to EBM resources (75%), a lack of time and patient overload (71.6%). The
      interview results confirmed the willingness of the hospital pharmacists to adopt
      EBM in their practice if necessary resources such as computers and internet
      connection were provided. CONCLUSION: The hospital pharmacists in Kuwait showed
      good attitude and willingness towards EBM, however, they need to acquire adequate
      knowledge and skills for applying it in "real life" practise. Using the current
      results, clinical implications were recommended to demonstrate how to overcome
      the barriers, wherein hospital pharmacists could be ready to practice EBM.

PMID- 29325556
TI  - Forecasting imbalances in the global health labor market and devising policy
      responses.
AB  - BACKGROUND: The High-Level Commission on Health Employment and Economic Growth
      released its report to the United Nations Secretary-General in September 2016. It
      makes important recommendations that are based on estimates of over 40 million
      new health sector jobs by 2030 in mostly high- and middle-income countries and a
      needs-based shortage of 18 million, mostly in low- and middle-income countries.
      This paper shows how these key findings were developed, the global policy
      dilemmas they raise, and relevant policy solutions. METHODS: Regression analysis
      is used to produce estimates of health worker need, demand, and supply.
      Projections of health worker need, demand, and supply in 2030 are made under the
      assumption that historical trends continue into the future. RESULTS: To deliver
      essential health services required for the universal health coverage target of
      the Sustainable Development Goal 3, there will be a need for almost 45 million
      health workers in 2013 which is projected to reach almost 53 million in 2030
      (across 165 countries). This results in a needs-based shortage of almost 17
      million in 2013. The demand-based results suggest a projected demand of 80
      million health workers by 2030. CONCLUSIONS: Demand-based analysis shows that
      high- and middle-income countries will have the economic capacity to employ tens
      of millions additional health workers, but they could face shortages due to
      supply not keeping up with demand. By contrast, low-income countries will face
      both low demand for and supply of health workers. This means that even if
      countries are able to produce additional workers to meet the need threshold, they
      may not be able to employ and retain these workers without considerably higher
      economic growth, especially in the health sector.

PMID- 29325557
TI  - Bidirectional associations between mothers' feeding practices and child eating
      behaviours.
AB  - BACKGROUND: This study examined bidirectional relationships between maternal
      feeding practices and child food responsiveness and satiety responsiveness from 2
      to 5 years. METHODS: Mothers (N = 207) reported their own feeding practices and
      child eating behaviours using validated questionnaires at child ages 2, 3.7, and
      5 years. Cross-lagged analyses were conducted to test for bidirectional effects,
      adjusting for child BMI z-score (based on measured weight and height) at 14
      months. RESULTS: Eating behaviours and feeding practices showed strong continuity
      across the three time points. Maternal feeding practices (higher reward for
      behaviour [beta = 0.12, p = 0.025] and lower covert restriction [beta = -0.14, p
      = 0.008]) were prospectively associated with higher food responsiveness.
      Conversely, increased child satiety responsiveness was primarily prospectively
      associated with mothers' feeding practices (increased structured meal timing
      [beta = 0.11, p = 0.038], overt [beta = 0.14, p = 0.010] and covert restriction
      [beta = 0.11, p = 0.022]). The only exception was family meal setting, which was
      prospectively negatively associated with satiety responsiveness (beta = -0.11, p
      = 0.035). CONCLUSION: While maternal feeding practices and child satiety and food
      responsiveness show strong continuity between child age 2 and 5 years, maternal
      feeding practices appear to be associated with child food responsiveness over
      time. Conversely, child satiety responsiveness, but not food responsiveness, may
      also be associated with maternal feeding practices over time. These results are
      consistent with interventions that provide feeding advice to parents on how to
      respond appropriately to individual child eating behaviour phenotype. TRIAL
      REGISTRATION: ACTRN12608000056392 . Registered 29 January 2008.

PMID- 29325559
TI  - Pangenome analyses of the wheat pathogen Zymoseptoria tritici reveal the
      structural basis of a highly plastic eukaryotic genome.
AB  - BACKGROUND: Structural variation contributes substantially to polymorphism within
      species. Chromosomal rearrangements that impact genes can lead to functional
      variation among individuals and influence the expression of phenotypic traits.
      Genomes of fungal pathogens show substantial chromosomal polymorphism that can
      drive virulence evolution on host plants. Assessing the adaptive significance of
      structural variation is challenging, because most studies rely on inferences
      based on a single reference genome sequence. RESULTS: We constructed and analyzed
      the pangenome of Zymoseptoria tritici, a major pathogen of wheat that evolved
      host specialization by chromosomal rearrangements and gene deletions. We used
      single-molecule real-time sequencing and high-density genetic maps to assemble
      multiple genomes. We annotated the gene space based on transcriptomics data that
      covered the infection life cycle of each strain. Based on a total of five
      telomere-to-telomere genomes, we constructed a pangenome for the species and
      identified a core set of 9149 genes. However, an additional 6600 genes were
      exclusive to a subset of the isolates. The substantial accessory genome encoded
      on average fewer expressed genes but a larger fraction of the candidate effector
      genes that may interact with the host during infection. We expanded our analyses
      of the pangenome to a worldwide collection of 123 isolates of the same species.
      We confirmed that accessory genes were indeed more likely to show deletion
      polymorphisms and loss-of-function mutations compared to core genes. CONCLUSIONS:
      The pangenome construction of a highly polymorphic eukaryotic pathogen showed
      that a single reference genome significantly underestimates the gene space of a
      species. The substantial accessory genome provides a cradle for adaptive
      evolution.

PMID- 29325558
TI  - Systematic target function annotation of human transcription factors.
AB  - BACKGROUND: Transcription factors (TFs), the key players in transcriptional
      regulation, have attracted great experimental attention, yet the functions of
      most human TFs remain poorly understood. Recent capabilities in genome-wide
      protein binding profiling have stimulated systematic studies of the hierarchical
      organization of human gene regulatory network and DNA-binding specificity of TFs,
      shedding light on combinatorial gene regulation. We show here that these data
      also enable a systematic annotation of the biological functions and functional
      diversity of TFs. RESULT: We compiled a human gene regulatory network for 384 TFs
      covering the 146,096 TF-target gene (TF-TG) relationships, extracted from over
      850 ChIP-seq experiments as well as the literature. By integrating this network
      of TF-TF and TF-TG relationships with 3715 functional concepts from six sources
      of gene function annotations, we obtained over 9000 confident functional
      annotations for 279 TFs. We observe extensive connectivity between TFs and
      Mendelian diseases, GWAS phenotypes, and pharmacogenetic pathways. Further, we
      show that TFs link apparently unrelated functions, even when the two functions do
      not share common genes. Finally, we analyze the pleiotropic functions of TFs and
      suggest that the increased number of upstream regulators contributes to the
      functional pleiotropy of TFs. CONCLUSION: Our computational approach is
      complementary to focused experimental studies on TF functions, and the resulting
      knowledge can guide experimental design for the discovery of unknown roles of TFs
      in human disease and drug response.

PMID- 29325561
TI  - Workforce patterns in the prevention of mother to child transmission of HIV in
      Cote d'Ivoire: a qualitative model.
AB  - BACKGROUND: Cote d'Ivoire continues to struggle with one of the highest rates of
      mother-to-child HIV transmission in West Africa, previously thought to be in part
      due to suboptimal workforce patterns. This study aimed to understand the process
      through which workforce patterns impact prevention of mother-to child
      transmission of HIV (PMTCT) program success, from the perspective of healthcare
      workers in Cote d'Ivoire. METHODS: A total of 142 semi-structured interviews were
      conducted with physicians, midwives, nurses, community counselors, social
      workers, pharmacists, management personnel and health aides from a nationally
      representative sample of 48 PMTCT sites across Cote d'Ivoire. RESULTS: Healthcare
      workers described three categories of workforce patterns that they perceived to
      be affecting PMTCT success: workforce inputs, healthcare roles and
      responsibilities, and facilitators of task performance. According to their
      descriptions, PMTCT success depends on the presence of an adequate and trained
      PMTCT workforce, with an interdisciplinary team of healthcare workers with
      flexible roles and expanded task responsibilities, and whose tasks are translated
      into patient care through collaboration, ongoing trainings, and appropriate
      motivators. CONCLUSIONS: This study provides a model for understanding the impact
      of workforce patterns on PMTCT success in Cote d'Ivoire and provides insight into
      workforce-related facilitators and barriers of program performance that should be
      targeted in future research and interventions. It highlights the importance of
      workforce integration and collaboration between healthcare workers.

PMID- 29325560
TI  - Feasibility and predictive performance of the Hendrich Fall Risk Model II in a
      rehabilitation department: a prospective study.
AB  - BACKGROUND: Falls are a common adverse event in both elderly inpatients and
      patients admitted to rehabilitation units. The Hendrich Fall Risk Model II
      (HIIFRM) has been already tested in all hospital wards with high fall rates, with
      the exception of the rehabilitation setting. This study's aim is to address the
      feasibility and predictive performances of HIIFRM in a hospital rehabilitation
      department. METHODS: A 6 months prospective study in a Italian rehabilitation
      department with patients from orthopaedic, pulmonary, and neurological
      rehabilitation wards. All admitted patients were enrolled and assessed within 24
      h of admission by means of the HIIFRM. The occurrence of falls was checked and
      recorded daily. HIIFRM feasibility was assessed as the percentage of successful
      administrations at admission. HIIFRM predictive performance was determined in
      terms of area under the Receiver Operating Characteristic (ROC) curve (AUC), best
      cutoff, sensitivity, specificity, positive and negative predictive values, along
      with their asymptotic 95% confidence intervals (95% CI). RESULTS: One hundred
      ninety-one patents were admitted. HIIFRM was feasible in 147 cases (77%), 11 of
      which suffered a fall (7.5%). Failures in administration were mainly due to
      bedridden patients (e.g. minimally conscious state, vegetative state). AUC was
      0.779(0.685-0.873). The original HIIFRM cutoff of 5 led to a sensitivity of 100%
      with a mere specificity of 49%(40-57%), thus suggesting using higher cutoffs.
      Moreover, the median score for non-fallers at rehabilitation units was higher
      than that reported in literature for geriatric non fallers. The best trade-off
      between sensitivity and specificity was obtained by using a cutoff of 8. This
      lead to sensitivity = 73%(46-99%), specificity = 72%(65-80%), positive predictive
      value = 17% and negative predictive value = 97%. These results support the use of
      the HIIFRM as a predictive tool. CONCLUSIONS: The HIIFRM showed satisfactory
      feasibility and predictive performances in rehabilitation wards. Based on both
      available literature and these results, the prediction of falls among all
      hospital wards, with high risk of falling, could be achieved by means of a unique
      tool and two different cutoffs: a standard cutoff of 5 in geriatric wards and an
      adjusted higher cutoff in rehabilitation units, with predictive performances
      similar to those of the best-preforming pathology specific tools for fall-risk
      assessment.

PMID- 29325562
TI  - Increased epicardial adipose tissue thickness is a predictor of new-onset
      diabetes mellitus in patients with coronary artery disease treated with high
      intensity statins.
AB  - BACKGROUND: Statins are widely used for lipid lowering in patients with coronary
      artery disease (CAD), but increasing evidence indicates an association between
      statin use and new-onset of diabetes mellitus (NODM). Epicardial adipose tissue
      (EAT) refers to the visceral fat surrounding the heart, which is associated with
      metabolic diseases. We sought to determine the association between EAT thickness
      and NODM in CAD patients treated with high-intensity statins. METHODS: We
      conducted a retrospective medical record review of CAD patients treated with high
      intensity statins for at least 6 months after percutaneous coronary intervention
      performed between January 2009 and June 2013 at Seoul National University Bundang
      Hospital. EAT thickness was measured by echocardiography using standardized
      methods. RESULTS: A total of 321 patients were enrolled, who received high
      intensity statins for a mean of 952 days; atorvastatin 40 mg in 204 patients
      (63.6%), atorvastatin 80 mg in 57 patients (17.8%), and rosuvastatin 20 mg in 60
      patients (18.7%). During the follow-up period of 3.9 +/- 1.7 years, NODM occurred
      in 40 patients (12.5%). On Cox proportional-hazard regression analysis, EAT
      thickness at systole [for each 1 mm: hazard ratio (HR) 1.580; 95% confidence
      interval (CI) 1.346-1.854; P < 0.001] and prediabetes at baseline (HR 4.321; 95%
      CI 1.998-9.349; P < 0.001) were the only independent predictors of NODM. Using
      binary cutoff values derived from the receiver operating characteristic curve
      analysis, EAT thickness at systole larger than 5.0 mm had an HR of 3.402 (95% CI
      1.751-6.611, P < 0.001), sensitivity of 52.5%, and specificity of 80.8% for
      predicting NODM. Also, patients with EAT thickness >= 5 mm and prediabetes at
      baseline had a 12.0-times higher risk of developing NODM compared to the risk
      noted in patients with EAT thickness < 5 mm and normal glucose tolerance at
      baseline. CONCLUSION: Epicardial adipose tissue thickness at systole is a
      consistent independent predictor of NODM in patients with CAD treated with high
      intensity statins. Such predictors may help physicians plan adequate surveillance
      for early detection of NODM.

PMID- 29325563
TI  - Healthcare information systems: the cognitive challenge.
AB  - BACKGROUND: Healthcare work is, to a considerable extent, cognitive.
      Subsequently, the analysis and the design of supporting technology must be
      sensitive to the cognitive and adaptive demands of the work and to the cognitive
      strategies employed by healthcare practitioners. Despite the vital role that
      cognition plays in healthcare work, current technocentric design approaches for
      healthcare technology do not account for it, failing to observe it during
      analysis and failing to develop support for it during design. MAIN BODY: By
      review and analysis of case studies, we show that healthcare systems developed
      without input from cognitive analysis and cognitive design fail to take account
      of important healthcare work processes and workflows. In contrast, systems
      developed with a cognitively-focused design strategy demonstrate how it is
      possible to introduce technology that supports and enhances the work strategies
      of those engaged in patient care. CONCLUSION: Significant problems emerge when
      technological support systems are developed without any serious and comprehensive
      attempt to understand the cognitive capabilities and skills deployed by those
      involved in patient care. In contrast, significant benefits accrue from taking
      full account of those cognitive capabilities and skills. Subsequently, the design
      and development of supporting technology must be sensitive to the cognitive
      demands of the work and the cognitive strategies employed by healthcare
      practitioners.

PMID- 29325566
TI  - Male breast cancer: diagnosis stages, treatment and survival in a country with
      limited resources (Burkina Faso).
AB  - BACKGROUND: Male breast cancer is a rare and less known disease. Therapeutic
      modalities affect survival. In Burkina Faso, male breast cancers are diagnosed in
      everyday practice, but the prognosis at short-, middle-, and long-term remains
      unknown. The objective of this study is to study the diagnosis stages,
      therapeutic modalities, and 5-year survival in male breast cancer at the General
      Surgery Unit of Yalgado Ouedraogo University Hospital from 1990 to 2009. METHODS:
      A cohort longitudinal study concerning cases of breast cancer diagnosed in man.
      Survival was assessed using the Kaplan-Meier method and survival curves were
      compared through the LogRank test. RESULTS: Fifty-one cases of male breast cancer
      were followed-up, i.e., 2.6% of all breast cancers. Stages III and IV represented
      88% of cases. Eleven patients (21.6%) were at metastatic stage. Patients were
      operated in 60.8% of cases. The surgery included axillary dissection in 25
      (80.6%) out of 31 cases. Lumpectomy was performed on 6.5% of patients (2 cases).
      Fifteen (29.4%) and 11 (21.6%) patients underwent chemotherapy and hormonal
      therapy, respectively. The FAC protocol was mostly used. Radiation therapy was
      possible in two cases. The median deadline for follow-up was 14.8 months. A local
      recurrence was noticed in 3.2% of cases. The overall 5-year survival rate was
      49.9%. The median survival was over 5 years for stages I and II. It was 54 down
      to 36 months for stages III and IV. CONCLUSION: Diagnosis is late. The lack of
      immunohistochemistry makes it difficult to define the proportion of their
      hormonal dependence. Surgery is the basic treatment. Five-year survival is slow
      and the median survival depends on the diagnosis stage. It can be improved
      through awareness-raising campaigns and the conduct of individual screening.

PMID- 29325564
TI  - Engineered recombinant protein products of the avian paramyxovirus type-1
      nucleocapsid and phosphoprotein genes for serological diagnosis.
AB  - BACKGROUND: Virulent Newcastle disease virus (NDV, avian Avulavirus-1, APMV-1)
      induces a highly contagious and lethal systemic disease in gallinaceous poultry.
      APMV-1 antibody detection is used for surveillance and to control vaccination,
      but is hampered by cross-reactivity to other subtypes of avian Avulaviruses. Data
      are lacking concerning the applicability of NDV V proteins as differential
      diagnostic marker to distinguish vaccinated from virus-infected birds (DIVA
      strategy). METHODS: Full length and C-terminally truncated nucleocapsid (NP)
      protein, and the unique C-terminal regions of the phospho- (P) and V proteins of
      the NDV LaSota strain were bacterially expressed as fusion proteins with the
      multimerization domain of the human C4 binding protein, and used as diagnostic
      antigens in indirect ELISA. RESULTS: When used as diagnostic antigen in indirect
      ELISAs, recombinant full-length proved to be a sensitive target to detect
      seroconversion in chickens after APMV-1 vaccination and infection, but revealed
      some degree of cross reactivity with sera raised against other APMV subtypes.
      Cross reactivity was abolished but also sensitivity decreased when employing a C
      terminal fragment of the NP of NDV as diagnostic antigen. Antibodies to the NDV V
      protein were mounted in poultry following NDV infection but also, albeit at lower
      rates and titers, after vaccination with attenuated NDV vaccines. V-specific
      seroconversion within the flock was incomplete and titers in individual bird
      transient. CONCLUSIONS: Indirect ELISA based on bacterially expressed recombinant
      full-length NP compared favorably with a commercial NDV ELISA based on whole
      virus antigen, but cross reactivity between the NP proteins of different APMV
      subtypes could compromise specificity. However, specificity increased when using
      a less conserved C-terminal fragment of NP instead. Moreover, a serological DIVA
      strategy built on the NDV V protein was not feasible due to reduced
      immunogenicity of the V protein and frequent use of live-attenuated NDV vaccines.

PMID- 29325565
TI  - Impact of social relationships on Alzheimer's memory impairment: mechanistic
      studies.
AB  - Alzheimer's disease (AD) is characterized by progressive memory and neuronal loss
      culminating in cognitive impairment that not only affects a person's living
      ability but also becomes a society's as well as a family's economic burden. AD is
      the most common form of dementia in older persons. It is expected that the number
      of people with AD dementia will increase dramatically in the next 30 years,
      projecting to 75 million in 2030 and 131.5 million in 2050 worldwide. So far, no
      sufficient evidence is available to support that any medicine is able to prevent
      or reverse the progression of the disease. Early studies have shown that social
      environment, particularly social relationships, can affect one's behavior and
      mental health. A study analyzing the correlation between loneliness and risk of
      developing AD revealed that lonely persons had higher risk of AD compared with
      persons who were not lonely. On the other hand, it has been reported that we can
      prevent cognitive decline and delay the onset of AD if we keep mentally active
      and frequently participate in social activities. In this review, we focus on the
      impact of social behaviors on the progression of cognitive deficit in animal
      models of AD with a particular emphasis on a mechanistic scheme that explains how
      social isolation exacerbates cognitive impairment and how social interaction with
      conspecifics rescues AD patients' memory deficit.

PMID- 29325567
TI  - Identifying older adults at risk of harm following elective surgery: a systematic
      review and meta-analysis.
AB  - BACKGROUND: Elective surgeries can be associated with significant harm to older
      adults. The present study aimed to identify the prognostic factors associated
      with the development of postoperative complications among older adults undergoing
      elective surgery. METHODS: Medline, EMBASE, CINAHL, Cochrane Central Register of
      Controlled Trials, and AgeLine were searched for articles published between
      inception and April 21, 2016. Prospective studies reporting prognostic factors
      associated with postoperative complications (composite outcome of medical and
      surgical complications), functional decline, mortality, post-hospitalization
      discharge destination, and prolonged hospitalization among older adults
      undergoing elective surgery were included. Study characteristics and prognostic
      factors associated with the outcomes of interest were extracted independently by
      two reviewers. Random effects meta-analysis models were used to derive pooled
      effect estimates for prognostic factors and incidences of adverse outcomes.
      RESULTS: Of the 5692 titles and abstracts that were screened for inclusion, 44
      studies (12,281 patients) reported on the following adverse postoperative
      outcomes: postoperative complications (n =28), postoperative mortality (n = 11),
      length of hospitalization (n = 21), functional decline (n = 6), and destination
      at discharge from hospital (n = 13). The pooled incidence of postoperative
      complications was 25.17% (95% confidence interval (CI) 18.03-33.98%, number
      needed to follow = 4). The geriatric syndromes of frailty (odds ratio (OR) 2.16,
      95% CI 1.29-3.62) and cognitive impairment (OR 2.01, 95% CI 1.44-2.81) were
      associated with developing postoperative complications; however, there was no
      association with traditionally assessed prognostic factors such as age (OR 1.07,
      95% CI 1.00-1.14) or American Society of Anesthesiologists status (OR 2.62, 95%
      CI 0.78-8.79). Besides frailty, other potentially modifiable prognostic factors,
      including depressive symptoms (OR 1.77, 95% CI 1.22-2.56) and smoking (OR 2.43,
      95% CI 1.32-4.46), were also associated with developing postoperative
      complications. CONCLUSION: Geriatric syndromes are important prognostic factors
      for postoperative complications. We identified potentially modifiable prognostic
      factors (e.g., frailty, depressive symptoms, and smoking) associated with
      developing postoperative complications that can be targeted preoperatively to
      optimize care.

PMID- 29325569
TI  - The relevance of clinical ethnography: reflections on 10 years of a cultural
      consultation service.
AB  - BACKGROUND: Training health professionals in culturally sensitive medical
      interviewing has been widely promoted as a strategy for improving intercultural
      communication and for helping clinicians to consider patients' social and
      cultural contexts and improve patient outcomes. Clinical ethnography encourages
      clinicians to explore the patient's explanatory model of illness, recourse to
      traditional and alternative healing practices, healthcare expectations and social
      context, and to use this information to negotiate a mutually acceptable treatment
      plan. However, while clinical ethnographic interviewing skills can be
      successfully taught and learned, the "real-world" context of medical practice may
      impose barriers to such patient-centered interviewing. Creating opportunities for
      role modeling and critical reflection may help overcome some of these barriers,
      and contribute to improved intercultural communication in healthcare. We report
      and reflect on a retrospective analysis of 10 years experience with a "cultural
      consultation service" (CCS) whose aim is to provide direct support to clinicians
      who encounter intercultural difficulties and to model the usefulness of clinical
      ethnographic interviewing for patient care. METHODS: We analyzed 236 cultural
      consultation requests in order to identify key patient, provider and consultation
      characteristics, as well as the cross cultural communication challenges that
      motivate health care professionals to request a cultural consultation. In
      addition, we interviewed 51 clinicians about their experience and satisfaction
      with the CCS. RESULTS: Requests for cultural consultations tended to involve
      patient care situations with complex social, cultural and medical issues. All
      patients had a migration background, two-thirds spoke French less than fluently.
      In over half the cases, patients had a high degree of social vulnerability,
      compromising illness management. Effective communication was hindered by language
      barriers and undetected or underestimated patient/provider differences in health
      related knowledge and beliefs. Clinicians were highly satisfied with the CCS, and
      appreciated both the opportunity to observe how clinical ethnographic
      interviewing is done and the increased knowledge they gained of their patients'
      context and perspective. CONCLUSIONS: A cultural consultation service such as
      ours can contribute to institutional cultural competence by drawing attention to
      the challenges of caring for diverse patient populations, identifying the
      training needs of clinicians and gaps in resource provision, and providing hands
      on experience with clinical ethnographic interviewing.

PMID- 29325570
TI  - De novo assembly of the complex genome of Nippostrongylus brasiliensis using
      MinION long reads.
AB  - BACKGROUND: Eukaryotic genome assembly remains a challenge in part due to the
      prevalence of complex DNA repeats. This is a particularly acute problem for
      holocentric nematodes because of the large number of satellite DNA sequences
      found throughout their genomes. These have been recalcitrant to most genome
      sequencing methods. At the same time, many nematodes are parasites and some
      represent a serious threat to human health. There is a pressing need for better
      molecular characterization of animal and plant parasitic nematodes. The advent of
      long-read DNA sequencing methods offers the promise of resolving complex genomes.
      RESULTS: Using Nippostrongylus brasiliensis as a test case, applying improved
      base-calling algorithms and assembly methods, we demonstrate the feasibility of
      de novo genome assembly matching current community standards using only MinION
      long reads. In doing so, we uncovered an unexpected diversity of very long and
      complex DNA sequences repeated throughout the N. brasiliensis genome, including
      massive tandem repeats of tRNA genes. CONCLUSION: Base-calling and assembly
      methods have improved sufficiently that de novo genome assembly of large complex
      genomes is possible using only long reads. The method has the added advantage of
      preserving haplotypic variants and so has the potential to be used in population
      analyses.

PMID- 29325568
TI  - PINK1 import regulation; a fine system to convey mitochondrial stress to the
      cytosol.
AB  - Insights from inherited forms of parkinsonism suggest that insufficient mitophagy
      may be one etiology of the disease. PINK1/Parkin-dependent mitophagy, which helps
      maintain a healthy mitochondrial network, is initiated by activation of the PINK1
      kinase specifically on damaged mitochondria. Recent investigation of this process
      reveals that import of PINK1 into mitochondria is regulated and yields a stress
      sensing mechanism. In this review, we focus on the mechanisms of mitochondrial
      stress-dependent PINK1 activation that is exerted by regulated import of PINK1
      into different mitochondrial compartments and how this offers strategies to
      pharmacologically activate the PINK1/Parkin pathway.

PMID- 29325571
TI  - Development of a hospital-based patient-reported outcome framework for lung
      cancer patients: a study protocol.
AB  - BACKGROUND: Patient-reported outcome (PRO) data is central to the delivery of
      quality health care. Establishing sustainable, reliable and cost-efficient
      methods for routine collection and integration of PRO data into health
      information systems is challenging. This protocol paper describes the design and
      structure of a study to develop and pilot test a PRO framework to systematically
      and longitudinally collect PRO data from a cohort of lung cancer patients at a
      comprehensive cancer centre in Australia. METHODS: Best-practice guidelines for
      developing registries aimed at collecting PROs informed the development of this
      PRO framework. Framework components included: achieving consensus on determining
      the purpose of the framework, the PRO measures to be included, the data
      collection time points and collection methods (electronic and paper),
      establishing processes to safeguard the quality of the data collected and to link
      the PRO framework to an existing hospital-based lung cancer clinical registry.
      Lung cancer patients will be invited to give feedback on the PRO measures (PROMs)
      chosen and the data collection time points and methods. Implementation of the
      framework will be piloted for 12 months. Then a mixed-methods approach used to
      explore patient and multidisciplinary perspectives on the feasibility of
      implementing the framework and linking it to the lung cancer clinical registry,
      its clinical utility, perceptions of data collection burden, and preliminary
      assessment of resource costs to integrate, implement and sustain the PRO
      framework. The PRO data set will include: a quality of life questionnaire (EORTC
      QLQ-C30) and the EORTC lung cancer specific module (QLQC-LC-13). These will be
      collected pre-treatment (baseline), 2, 6 and 12 months post-baseline. Also, four
      social isolation questions (PROMIS) will be collected at baseline. DISCUSSION:
      Identifying and deciding on the overall purpose, clinical utility of data and
      which PROs to collect from patients requires careful consideration. Our study
      will explore how PRO data collection processes that link to a clinical data set
      can be developed and integrated; how PRO systems that are easy for patients to
      complete and professionals to use in practice can be achieved, and will provide
      indicative costs of developing and integrating a longitudinal PRO framework into
      routine hospital data collection systems. TRIAL REGISTRATION: This study is not a
      clinical trial and is therefore not registered in any trial registry. However, it
      has received human research ethics approval (LNR/16/PMCC/45).

PMID- 29325572
TI  - Modeling the relationship between women's perceptions and future intention to use
      institutional maternity care in the Western Highlands of Guatemala.
AB  - BACKGROUND: Despite global gains, women in hard-to-reach areas are at a
      relatively higher risk of death and disability related to childbirth. Traditional
      methods of measuring satisfaction may mask negative experiences (such as
      disrespect and abuse) that can drive down demand for institutional care. Better
      measurement of women's perceptions of care quality, especially among marginalized
      populations with historically low utilization of institutional care, are needed
      to inform how to improve services and foster greater utilization of (potentially
      life-saving) clinical care. METHODS: A population-based household survey was
      conducted in 15 purposively selected villages in the rural Western Highlands of
      Guatemala among women who gave birth to a child within the last 5 years.
      Demographic and health information including experiences and perceptions of
      maternity care were collected. Two sets of nested multivariate logistic
      regression models were estimated to identify factors associated with future
      intention to give birth in a health facility, separately among women who gave
      birth to their last child at home and women who gave birth to their last child in
      a facility. The independent variables of interest were access to care, perceived
      need for maternity care, and two measures of perceived quality: satisfaction with
      last birth and disrespect and abuse (perceived or experienced). Thematic analysis
      was performed on open-ended responses. RESULTS: Perceived need for facility-based
      childbirth services and satisfaction with last childbirth experience, either at
      home or in a facility, emerged as the key factors influencing intention to give
      birth in a health institution in the future. Among the facility birth group,
      reporting disrespect and abuse is a deterrent to seeking facility-based care in
      the future. However, select perceptions of disrespect and abuse did not have an
      association with future intention (among the home birth group). CONCLUSIONS:
      Women's perceptions of care quality influence care-seeking. Women who feel they
      were mistreated in health facilities are more likely to avoid or delay seeking
      care in the future. Health systems need to reinforce trust and positive
      perceptions of respectful care. Developing better measures of women's perceptions
      of maternity care experiences among indigenous populations in Guatemala can
      inform improvements in care provision.

PMID- 29325574
TI  - Applied global health diplomacy: profile of health diplomats accredited to the
      UNITED STATES and foreign governments.
AB  - BACKGROUND: Global health diplomacy (GHD) is a burgeoning field bridging the
      priorities of global health and foreign affairs. Given the increasing need to
      mobilize disparate global health stakeholders coupled with the need to design
      complex public health partnerships to tackle issues of international concern,
      effective and timely cooperation among state actors is critical. Health Attaches
      represent this coordination focal point and are key diplomatic professionals at
      the forefront of GHD. Despite their unique mandate, little is published about
      this profession and the perspectives of those who work in the field. METHODS:
      Through purposive sampling, we performed in-depth qualitative interviews with
      seven Health Attaches: three foreign Health Attaches accredited to the United
      States and four U.S. Health Attaches accredited to foreign governments. Our
      interviews explored four key topics: the role and mission of Health Attaches,
      skills needed to perform GHD, examples of successes and challenges in
      accomplishing their respective missions, and suggestions for the future
      development of the diplomatic profession. RESULTS: We identified several lessons
      to apply to the growing field of GHD. First, GHD actors need to receive
      appropriate training to successfully negotiate the intersection of global health
      and foreign affairs. Participants suggested several areas of training that would
      benefit GHD actors: diplomacy and negotiation, applied science, and cross
      cultural competency. Second, participants articulated the need for a career path
      for GHD practitioners, increased opportunities for on-the-job training and
      mentored experiences, and GHD competencies with defined levels of mastery that
      can be used in occupational evaluation and career development. CONCLUSIONS: Our
      findings indicate that skills in diplomacy and negotiation, applied science, and
      cross cultural competency are essential for the statecraft of Health Attaches.
      Additionally, establishing a clear career pathway for Health Attaches is critical
      for future maturation of the profession and for fostering effective global health
      action that aligns public health and foreign diplomacy outcomes. Achieving these
      goals would ensure that this special cadre of diplomats could effectively
      practice GHD and would also better position Health Attaches to take the lead in
      advancing shared global health goals among nation states in a new era of twenty
      first century diplomacy.

PMID- 29325575
TI  - Routinely collected data for randomized trials: promises, barriers, and
      implications.
AB  - BACKGROUND: Routinely collected health data (RCD) are increasingly used for
      randomized controlled trials (RCTs). This can provide three major benefits:
      increasing value through better feasibility (reducing costs, time, and
      resources), expanding the research agenda (performing trials for research
      questions otherwise not amenable to trials), and offering novel design and data
      collection options (e.g., point-of-care trials and other designs directly
      embedded in routine care). However, numerous hurdles and barriers must be
      considered pertaining to regulatory, ethical, and data aspects, as well as the
      costs of setting up the RCD infrastructure. Methodological considerations may be
      different from those in traditional RCTs: RCD are often collected by individuals
      not involved in the study and who are therefore blinded to the allocation of
      trial participants. Another consideration is that RCD trials may lead to greater
      misclassification biases or dilution effects, although these may be offset by
      randomization and larger sample sizes. Finally, valuable insights into external
      validity may be provided when using RCD because it allows pragmatic trials to be
      performed. METHODS: We provide an overview of the promises, challenges, and
      potential barriers, methodological implications, and research needs regarding RCD
      for RCTs. RESULTS: RCD have substantial potential for improving the conduct and
      reducing the costs of RCTs, but a multidisciplinary approach is essential to
      address emerging practical barriers and methodological implications. CONCLUSIONS:
      Future research should be directed toward such issues and specifically focus on
      data quality validation, alternative research designs and how they affect outcome
      assessment, and aspects of reporting and transparency.

PMID- 29325576
TI  - Reanalysis of Chinese Treponema pallidum samples: all Chinese samples cluster
      with SS14-like group of syphilis-causing treponemes.
AB  - OBJECTIVE: Treponema pallidum subsp. pallidum (TPA) is the causative agent of
      syphilis. Genetic analyses of TPA reference strains and human clinical isolates
      have revealed two genetically distinct groups of syphilis-causing treponemes,
      called Nichols-like and SS14-like groups. So far, no genetic intermediates, i.e.
      strains containing a mixed pattern of Nichols-like and SS14-like genomic
      sequences, have been identified. Recently, Sun et al. (Oncotarget 2016.
      https://doi.org/10.18632/oncotarget.10154 ) described a new "phylogenetic group"
      (called Lineage 2) among Chinese TPA strains. This lineage exhibited a "mosaic
      genomic structure" of Nichols-like and SS14-like lineages. RESULTS: We reanalyzed
      the primary sequencing data (Project Number PRJNA305961) from the Sun et al.
      publication with respect to the molecular basis of Lineage 2. While Sun et al.
      based the analysis on several selected genomic single nucleotide variants (SNVs)
      and a subset of highly variable but phylogenetically poorly informative genes,
      which may confound the phylogenetic analysis, our reanalysis primarily focused on
      a complete set of whole genomic SNVs. Based on our reanalysis, only two separate
      TPA clusters were identified: one consisted of Nichols-like TPA strains, the
      other was formed by the SS14-like TPA strains, including all Chinese strains.

PMID- 29325573
TI  - Genetic diversity of three surface protein genes in Plasmodium malariae from
      three Asian countries.
AB  - BACKGROUND: Genetic diversity of the three important antigenic proteins, namely
      thrombospondin-related anonymous protein (TRAP), apical membrane antigen 1
      (AMA1), and 6-cysteine protein (P48/45), all of which are found in various
      developmental stages of Plasmodium parasites is crucial for targeted vaccine
      development. While studies related to the genetic diversity of these proteins are
      available for Plasmodium falciparum and Plasmodium vivax, barely enough
      information exists regarding Plasmodium malariae. The present study aims to
      demonstrate the genetic variations existing among these three genes in P.
      malariae by analysing their diversity at nucleotide and protein levels. METHODS:
      Three surface protein genes were isolated from 45 samples collected in Thailand
      (N = 33), Myanmar (N = 8), and Lao PDR (N = 4), using conventional polymerase
      chain reaction (PCR) assay. Then, the PCR products were sequenced and analysed
      using BioEdit, MEGA6, and DnaSP programs. RESULTS: The average pairwise
      nucleotide diversities (pi) of P. malariae trap, ama1, and p48/45 were 0.00169,
      0.00413, and 0.00029, respectively. The haplotype diversities (Hd) of P. malariae
      trap, ama1, and p48/45 were 0.919, 0.946, and 0.130, respectively. Most of the
      nucleotide substitutions were non-synonymous, which indicated that the genetic
      variations of these genes were maintained by positive diversifying selection,
      thus, suggesting their role as a potential target of protective immune response.
      Amino acid substitutions of P. malariae TRAP, AMA1, and P48/45 could be
      categorized to 17, 20, and 2 unique amino-acid variants, respectively. For
      further vaccine development, carboxyl terminal of P48/45 would be a good
      candidate according to conserved amino acid at low genetic diversity (pi = 0.2
      0.3). CONCLUSIONS: High mutational diversity was observed in P. malariae trap and
      ama1 as compared to p48/45 in P. malariae samples isolated from Thailand,
      Myanmar, and Lao PDR. Taken together, these results suggest that P48/45 might be
      a good vaccine candidate against P. malariae infection because of its
      sufficiently low genetic diversity and highly conserved amino acids especially on
      the carboxyl end.

PMID- 29325577
TI  - Dynamic kinematics of the glenohumeral joint in shoulders with rotator cuff
      tears.
AB  - BACKGROUND: No clear trend has emerged from the literature regarding three
      dimensional (3D) translations of the humerus relative to the scapula in shoulders
      with rotator cuff tears (RCTs). The purpose of this study was to evaluate the
      kinematics of RCT shoulders using 3D-to-two-dimensional (2D) model-to-image
      registration techniques. METHODS: Dynamic glenohumeral kinematics during scapular
      plane abduction and axial rotation were analyzed in 11 RCT patients and 10
      healthy control subjects. We measured the 3D kinematic parameters of glenohumeral
      joints using X-ray images and CT-derived digitally reconstructed radiographs.
      RESULTS: For scapular plane abduction, the humeral head center was positioned
      significantly more medially in shoulders with RCTs than in controls at 135
      degrees  of humeral abduction (p = 0.02; RCTs versus controls: - 0.9 +/- 1.6
      versus 0.3 +/- 1.3 mm). There was no significant difference in the
      superior/inferior translation of the humeral head center (p = 0.99). For axial
      rotation in adducted position, the humeral head center was positioned
      significantly more anteriorly in shoulders with RCTs than in controls at - 30
      degrees  of glenohumeral external rotation (p < 0.0001; RCTs versus controls: 3.0
      +/- 1.7 versus 0.3 +/- 1.5 mm). CONCLUSIONS: This study revealed the kinematics
      of shoulders with large to massive full-thickness RCTs: the humeral head center
      showed a medial shift at the late phase of scapular plane full abduction, and an
      anterior shift at the internal rotation position during full axial rotation. The
      kinematic data in this study, which describe the patterns of movement of
      shoulders with large to massive full-thickness RCTs, provide valuable information
      for future studies investigating glenohumeral translations in other pathological
      conditions of the shoulder. For clinical relevance, quantitative assessment of
      the dynamic kinematics of shoulders with RCTs might be a therapeutic indicator
      for achieving functional restoration.

PMID- 29325578
TI  - Effects of a peer-led Walking In ScHools intervention (the WISH study) on
      physical activity levels of adolescent girls: a cluster randomised pilot study.
AB  - BACKGROUND: School-based interventions may be effective at increasing levels of
      physical activity (PA) among adolescents; however, there is a paucity of evidence
      on whether walking can be successfully promoted to increase PA in this age group.
      This pilot study aimed to assess the effects of a 12-week school-based peer-led
      brisk walking programme on levels of school-time PA post intervention. METHODS:
      Female participants, aged 11-13 years, were recruited from six post-primary
      schools in Northern Ireland. Participants were randomized by school (cluster) to
      participate in regular 10-15-min peer-led brisk walks throughout the school week
      (the WISH study) (n = 101, two schools) or to continue with their usual PA (n =
      98, four schools). The primary outcome measure was school-time PA post
      intervention (week 12), assessed objectively using an Actigraph accelerometer.
      Secondary outcome measures included anthropometry, cardiorespiratory fitness and
      psychosocial measures. Changes in PA data between baseline (T0) and end of
      intervention (week 12) (T1) were analysed using a mixed between-within subjects
      analysis of variance with one between (group) and one within (time) subjects
      factor, with two levels. RESULTS: Of 199 participants recruited (mean age = 12.4
      +/- 0.6 years, 27% overweight/obese), 187 had valid accelerometer data for
      inclusion in subsequent analysis. A significant interaction effect was observed
      for changes in light intensity PA across the school day (p = 0.003), with those
      in the intervention increasing their light intensity PA by 8.27 mins/day compared
      with a decrease of 2.14 mins/day in the control group. No significant
      interactions were observed for the other PA measures across the intervention.
      Intervention effects on school-time PA were not sustained four months post
      intervention. CONCLUSIONS: The intervention increased daily light intensity PA
      behaviour in these adolescent girls but did not change moderate to vigorous
      physical activity (MVPA). These findings suggest that a school-based brisk
      walking intervention may be feasible and can change PA behaviour in the short
      term, but it is possible that the self-selected walking speeds determined by a
      peer-leader may not be sufficient to reach MVPA in this age group. Further
      research is needed to evaluate the potential of school-based brisk walking to
      contribute to MVPA in adolescent girls. TRIAL REGISTRATION: ClinicalTrials.gov,
      NCT02871830 . Registered on 16 August 2016).

PMID- 29325579
TI  - The return of the Iberian lynx to Portugal: local voices.
AB  - BACKGROUND: Ethnographic research can help to establish dialog between
      conservationists and local people in reintroduction areas. Considering that
      predator reintroductions may cause local resistance, we assessed attitudes of
      different key actor profiles to the return of the Iberian lynx (Lynx pardinus) to
      Portugal before reintroduction started in 2015. We aimed to characterize a social
      context from an ethnoecological perspective, including factors such as local
      knowledge, perceptions, emotions, and opinions. METHODS: We conducted semi
      structured interviews (n = 131) in three different protected areas and observed
      practices and public meetings in order to describe reintroduction contestation,
      emotional involvement with the species, and local perceptions about conservation.
      Detailed content data analysis was undertaken and an open-ended codification of
      citations was performed with the support of ATLAS.ti. Besides the qualitative
      analyses, we further explored statistic associations between knowledge and
      opinions and compared different geographical areas and hunters with non-hunters
      among key actors. RESULTS: Local ecological knowledge encompassed the lynx but
      was not shared by the whole community. Both similarities and differences between
      local and scientific knowledge about the lynx were found. The discrepancies with
      scientific findings were not necessarily a predictor of negative attitudes
      towards reintroduction. Contestation issues around reintroduction differ between
      geographical areas but did not hinder an emotional attachment to the species and
      its identification as a territory emblem. Among local voices, financial
      compensation was significantly associated to hunters and nature tourism was cited
      the most frequent advantage of lynx presence. Materialistic discourses existed in
      parallel with non-economic factors and the existence of moral agreement with its
      protection. The considerable criticism and reference to restrictions by local
      actors concerning protected areas and conservation projects indicated the
      experience of an imposed model of nature conservation. Opinions about
      participation in the reintroduction process highlighted the need for a closer
      dialog between all actors and administration. CONCLUSIONS: Local voices analyzed
      through an ethnoecological perspective provide several views on reintroduction
      and nature conservation. They follow two main global trends of environmental
      discourse: (1) nature becomes a commodified object to exploit while contestation
      about wildlife is centered on financial return and (2) emblematic wild species
      create an emotional attachment, become symbolic, and gather moral agreement for
      nature protection. Lynx reintroduction has been not only just a nature protection
      theme but also a negotiation process with administration. Western rural
      communities are not the "noble savages" and nature protectors as are other
      traditional groups, and actors tend to claim for benefits in a situation of
      reintroduction. Both parties comprehend a similar version of appropriated nature.
      Understanding complexity and diverse interests in local communities are useful in
      not oversimplifying local positions towards predator conservation. We recommend
      that professional conservation teams rethink their image among local populations
      and increase proximity with different types of key actors.

PMID- 29325580
TI  - The predictive prognostic factors for polymyositis/dermatomyositis-associated
      interstitial lung disease.
AB  - BACKGROUND: Interstitial lung disease (ILD) is the principal cause of death in
      polymyositis/dermatomyositis (PM/DM). Here we investigated prognostic factors for
      death and serious infection in PM/DM-ILD using the multicenter database. METHODS:
      We retrospectively reviewed baseline demographic, clinical and laboratory
      findings, treatment regimens and outcomes in patients with PM/DM-ILD. The
      distribution of ILD lesions was evaluated in four divided lung zones of high
      resolution computed tomography images. RESULTS: Of 116 patients with PM/DM-ILD,
      14 died within 6 months from the diagnosis. As independent risk factors for early
      death, extended ILD lesions in upper lung fields (odds ratio (OR) 8.01, p =
      0.016) and hypocapnia (OR 6.85, p = 0.038) were identified. Serious infection was
      found in 38 patients, including 11 patients who died of respiratory or multiple
      infections. The independent risk factors were high serum KL-6 (OR 3.68, p =
      0.027), high initial dose of prednisolone (PSL) (OR 4.18, p = 0.013), and
      combination immunosuppressive therapies (OR 5.51, p < 0.001). CONCLUSION: The
      present study shows the progression of ILD at baseline is the most critical for
      survival and that infection, especially respiratory infection, is an additive
      prognostic factor under the potent immunosuppressive treatment.

PMID- 29325582
TI  - Urinary angiostatin, CXCL4 and VCAM-1 as biomarkers of lupus nephritis.
AB  - BACKGROUND: The aim was to study urinary angiostatin, CXC chemokine ligand 4
      (CXCL4) and vascular cell adhesion molecule-1 (VCAM-1) as biomarkers of renal
      disease in systemic lupus erythematosus (SLE). METHOD: Patients who fulfilled >=
      4 American College of Rheumatology (ACR) criteria for SLE with active renal,
      active non-renal or inactive disease, and a group of healthy controls were
      studied. Urine samples were assayed for angiostatin, CXCL4 and VCAM-1 by ELISA,
      and normalized by creatinine. Receiver operating characteristic analysis was
      performed to obtain the best cutoff values to calculate the performance of these
      markers in differentiating the different groups of patients as compared to anti
      double-stranded DNA (anti-dsDNA) and complement C3. Correlation between these
      urinary biomarkers and various renal parameters was also tested. RESULTS:
      Patients with SLE (n = 227; 80 with inactive SLE, 67 with active non-renal
      disease and 80 with active renal disease; 94% women; age 39.2 +/- 13.8 years) and
      53 controls (96% women) were studied. All were ethnic Chinese. Urinary
      angiostatin, CXCL4 and VCAM-1 (normalized for creatinine) were significantly
      higher in patients with active renal disease than in patients with active non
      renal disease, patients with inactive SLE and controls. These markers correlated
      significantly with total SLE disease activity index (SLEDAI) and renal SLEDAI
      scores, and with the urinary protein-to-creatinine ratio. Urine angiostatin
      exhibited higher specificity and sensitivity in differentiating active renal from
      active non-renal SLE (area under the curve (AUC) 0.87) than serum anti-dsDNA/C3.
      Urine CXCL4 (AUC 0.64) and VCAM-1 (AUC 0.73), on the other hand, performed
      similarly to anti-dsDNA/C3. All three markers performed comparably to anti
      dsDNA/C3 in distinguishing active from inactive SLE. In a subgroup of 68 patients
      with paired renal biopsy, the urinary levels of these proteins did not differ
      significantly between the proliferative and non-proliferative types of lupus
      nephritis. Urinary CXCL4 and VCAM-1 correlated significantly with the histologic
      activity score, and urinary angiostatin correlated significantly with proteinuria
      in this subgroup. CONCLUSIONS: Urinary angiostatin, CXCL4 and VCAM-1 are
      potential biomarkers for SLE, in particular lupus nephritis. Further longitudinal
      studies are necessary to delineate the performance of these markers in predicting
      renal flares and prognosis in SLE patients.

PMID- 29325581
TI  - Haemophilus is overrepresented in the nasopharynx of infants hospitalized with
      RSV infection and associated with increased viral load and enhanced mucosal CXCL8
      responses.
AB  - BACKGROUND: While almost all infants are infected with respiratory syncytial
      virus (RSV) before the age of 2 years, only a small percentage develops severe
      disease. Previous studies suggest that the nasopharyngeal microbiome affects
      disease development. We therefore studied the effect of the nasopharyngeal
      microbiome on viral load and mucosal cytokine responses, two important factors
      influencing the pathophysiology of RSV disease. To determine the relation between
      (i) the microbiome of the upper respiratory tract, (ii) viral load, and (iii)
      host mucosal inflammation during an RSV infection, nasopharyngeal microbiota
      profiles of RSV infected infants (< 6 months) with different levels of disease
      severity and age-matched healthy controls were determined by 16S rRNA marker gene
      sequencing. The viral load was measured using qPCR. Nasopharyngeal CCL5, CXCL10,
      MMP9, IL6, and CXCL8 levels were determined with ELISA. RESULTS: Viral load in
      nasopharyngeal aspirates of patients associates significantly to total
      nasopharyngeal microbiota composition. Healthy infants (n = 21) and RSV patients
      (n = 54) display very distinct microbial patterns, primarily characterized by a
      loss in commensals like Veillonella and overrepresentation of opportunistic
      organisms like Haemophilus and Achromobacter in RSV-infected individuals.
      Furthermore, nasopharyngeal microbiota profiles are significantly different based
      on CXCL8 levels. CXCL8 is a chemokine that was previously found to be indicative
      for disease severity and for which we find Haemophilus abundance as the strongest
      predictor for CXCL8 levels. CONCLUSIONS: The nasopharyngeal microbiota in young
      infants with RSV infection is marked by an overrepresentation of the genus
      Haemophilus. We present that this bacterium is associated with viral load and
      mucosal CXCL8 responses, both which are involved in RSV disease pathogenesis.

PMID- 29325584
TI  - Adenomatoid tumor of the testis mimicking malignant testicular cancer on
      multiparametric ultrasound.
AB  - BACKGROUND: Adenomatoid tumor is one of the most common histological subtypes of
      paratesticular cancer arising from the epididymis. In very rare cases, these
      tumors appear as intratesticular lesions originating in the tunica albuginea,
      representing a diagnostic challenge. CASE PRESENTATION: We present a case of a 51
      year-old man with a small (0.9 cm) hyperechoic lesion of the left testicle
      mimicking testicular cancer on multiparametric ultrasound. The lesion was
      localized in the peripheral zone, confirming vascularization and increased
      stiffness on contrast-enhanced ultrasound and real-time elastography.
      Preoperative tumor markers and hormone levels were within normal ranges. Staging
      computed tomography was negative. Organ-sparing surgery with tumor enucleation
      and frozen section analysis was performed, confirming testicular adenomatoid
      tumor. CONCLUSION: Currently, no typical ultrasound features can definitively
      distinguish intratesticular adenomatoid tumors from malignant testicular masses.
      Thus, a surgical approach is almost always considered in such a case for both
      diagnostic and therapeutic purposes.

PMID- 29325583
TI  - An integrated-delivery-of-care approach to improve patient reported physical
      function and mental wellbeing after orthopedic trauma: study protocol for a
      randomized controlled trial.
AB  - BACKGROUND: Orthopedic trauma injury impacts nearly 2.8 million people each year.
      Despite surgical improvements and excellent survivorship rates, many patients
      experience poor quality of life (QOL) outcomes years later. Psychological
      distress commonly occurs after injury. Distressed patients more frequently
      experience rehospitalizations, pain medication dependence, and low QOL. This
      study was developed to test whether an integrative care approach (IntCare; ten
      step program of emotional support, education, customized resources, and medical
      care) was superior to usual care (UsCare). The primary aim was to assess patient
      functional QOL (objective and patient-reported outcomes) with secondary
      objectives encompassing emotional wellbeing and hospital outcomes. The primary
      outcome was the Lower Extremity Gain Scale score. METHODS/DESIGN: A single
      blinded, single-center, repeated measures, randomized controlled study is being
      conducted with 112 orthopedic trauma patients aged 18-85 years. Patients
      randomized to the IntCare group have completed or are receiving a guided ten-step
      support program during acute care and at follow-up outpatient visits. The UsCare
      group is being provided the standard of care. Patient-reported outcomes and
      objective functional measures are collected at the hospital and at weeks 2, 6,
      and 12 and months 6 and 12 post surgery. The main study outcomes are changes in
      Patient-Reported Outcomes Measurement Information System (PROMIS) questionnaires
      of Physical Function quality of life, Satisfaction with Social Roles, and
      Positive-Illness Impact, Post-Traumatic Stress Disorder Check List, and the Tampa
      Scale of Kinesiophobia-11 from baseline to month 12. Secondary outcomes are
      changes in objective functional measures of the Lower Extremity Gain Scale,
      handgrip strength, and range of motion of major joints from week 2 to month 12
      post surgery. Clinical outcomes include hospital length of stay, medical
      complications, rehospitalizations, psychological measures, and use of pain
      medications. A mixed model repeated measures approach assesses the main effects
      of treatment and time on outcomes, as well as their interaction (treatment *
      time). DISCUSSION: The results from this study will help determine whether an
      integrative care approach during recovery from traumatic orthopedic injury can
      improve the patient perceptions of physical function and emotional wellbeing
      compared to usual trauma care. Additionally, this study will assess the ability
      to reduce the incidence or severity of psychological distress and mitigate
      medical complications, readmissions, and reduction of QOL after injury. TRIAL
      REGISTRATION: ClinicalTrials.gov, NCT02591472 . Registered on 28 October 2015.

PMID- 29325585
TI  - Clinical research ethics review process in Lebanon: efficiency and functions of
      research ethics committees - results from a descriptive questionnaire-based
      study.
AB  - BACKGROUND: Clinical trials conducted in Lebanon are increasing. However, little
      is known about the performance of research ethics committees (RECs) in charge of
      reviewing the research protocols. This study aimed to assess the level of
      adherence to the ethics surrounding the conduct of clinical trials and
      perceptions of team members regarding roles of the RECs during the conduct of
      clinical trials in Lebanon. The research question was: Are RECs adherent to the
      ethics surrounding the conduct of clinical trials (chapters II and IV in
      'Standards and Operational Guidance for Ethics Review of Health-related Research
      with Human Participants' in Lebanon?' METHODS: This was a quantitative and
      descriptive questionnaire-based study conducted among RECs of university
      hospitals in Lebanon. The questionnaire had to be completed online and included
      general questions in addition to items reflecting the different aspects of a REC
      performance and effectiveness. All the questionnaire was assigned a total score
      of 175 points. General information and questions assigned point values/scores
      were analysed using descriptive statistics: frequency and percentage, mean score
      +/- standard deviation. RESULTS: Ten RECs participated in the study (52 persons:
      four chairs, one vice-president, 47 ordinary members). Forty-seven (90.4%) had
      previous experience with clinical research and 30 (57.7%) had a diploma or had
      done a training in research ethics. Forty-one percent confirmed that they were
      required to have a training in research ethics. All RECs had a policy for
      disclosing and managing potential conflicts of interest for its members, but
      71.8% of participants reported the existence of such a policy for researchers.
      Thirty-three point three percent reported that the RECs had an anti-bribery
      policy. The questionnaire mean score was 129.6 +/- 22.3/175 points reflecting
      thus an excellent adherence to international standards. CONCLUSION: Inadequate
      training of REC members and the lack of anti-bribery policies should be resolved
      to improve their performance.

PMID- 29325587
TI  - Human echinostomiasis: a case report.
AB  - BACKGROUND: Echinostomiasis is a food-borne infection caused by an intestinal
      trematodes belonging to the family Echinostomatidae. They infect the
      gastrointestinal tract of humans. Patients are usually asymptomatic. However,
      with heavy infections, the worms can produce catarrhal inflammation with mild
      ulceration and the patient may experience abdominal pain, anorexia, nausea,
      vomiting, diarrhea and weight loss. Infection are associated with common
      sociocultural practices of eating raw or insufficiently cooked mollusks and fish.
      CASE PRESENTATION: We report a first case of echinostomiasis from Nepal in a 62
      years old, hindu male who presented to Tribhuvan University Teaching Hospital,
      Kathmandu with a complaint of abdominal pain and distension with vomiting on and
      off for 3-4 months. He had history of consumption of insufficiently cooked fish
      and snail with alcohol. During endoscopy, an adult flat worm was seen with mild
      portal hypertensive gastropathy (McCormack's classification) and erosive
      duodenopathy. The adult worm was identified as Echinostoma species based on its
      morphology and characteristic ova found on stool routine microscopic examination
      of the patient. Patient was treated with praziquantel 40 mg/kg (single dose)
      which is the drug of choice for Echinostoma species infection by which he got
      improved and on follow up stool examination after 2 weeks revealed no ova of
      Echinostoma species. CONCLUSIONS: The patients having history of consumption of
      insufficiently cooked snail and fish with suggestive clinical features of
      echinostomiasis should be suspected by physicians and ova of Echinostoma species
      should be searched by trained microscopists. An epidemiological survey is
      required to know the exact burden of Echinostoma species infection in the place
      where people have habit of eating insufficiently cooked fish and snails, as it
      can be endemic in that community or geographical area.

PMID- 29325586
TI  - High frequency percussive ventilation increases alveolar recruitment in early
      acute respiratory distress syndrome: an experimental, physiological and CT scan
      study.
AB  - BACKGROUND: High frequency percussive ventilation (HFPV) combines diffusive (high
      frequency mini-bursts) and convective ventilation patterns. Benefits include
      enhanced oxygenation and hemodynamics, and alveolar recruitment, while providing
      hypothetic lung-protective ventilation. No study has investigated HFPV-induced
      changes in lung aeration in patients with early acute respiratory distress
      syndrome (ARDS). METHODS: Eight patients with early non-focal ARDS were enrolled
      and five swine with early non-focal ARDS were studied in prospective computed
      tomography (CT) scan and animal studies, in a university-hospital tertiary ICU
      and an animal laboratory. Patients were optimized under conventional "open-lung"
      ventilation. Lung CT was performed using an end-expiratory hold (Conv) to assess
      lung morphology. HFPV was applied for 1 hour to all patients before new CT scans
      were performed with end-expiratory (HFPV EE) and end-inspiratory (HFPV EI) holds.
      Lung volumes were determined after software analysis. At specified time points,
      blood gases and hemodynamic data were collected. Recruitment was defined as a
      change in non-aerated lung volumes between Conv, HFPV EE and HFPV EI. The main
      objective was to verify whether HFPV increases alveolar recruitment without lung
      hyperinflation. Correlation between pleural, upper airways and HFPV-derived
      pressures was assessed in an ARDS swine-based model. RESULTS: One-hour HFPV
      significantly improved oxygenation and hemodynamics. Lung recruitment
      significantly rose by 12.0% (8.5-18.0%), P = 0.05 (Conv-HFPV EE) and 12.5% (9.3
      16.8%), P = 0.003 (Conv-HFPV EI). Hyperinflation tended to increase by 2.0% (0.5
      2.5%), P = 0.89 (Conv-HFPV EE) and 3.0% (2.5-4.0%), P = 0.27 (Conv-HFPV EI). HFPV
      hyperinflation correlated with hyperinflated and normally-aerated lung volumes at
      baseline: r = 0.79, P = 0.05 and r = 0.79, P = 0.05, respectively (Conv-HFPV EE);
      and only hyperinflated lung volumes at baseline: r = 0.88, P = 0.01 (Conv-HFPV
      EI). HFPV CT-determined tidal volumes reached 5.7 (1.1-8.1) mL.kg-1 of ideal body
      weight (IBW). Correlations between pleural and HFPV-monitored pressures were
      acceptable and end-inspiratory pleural pressures remained below 25cmH20.
      CONCLUSIONS: HFPV improves alveolar recruitment, gas exchanges and hemodynamics
      of patients with early non-focal ARDS without relevant hyperinflation. HFPV
      derived pressures correlate with corresponding pleural or upper airways
      pressures. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02510105 . Registered on 1
      June 2015. The trial was retrospectively registered.

PMID- 29325588
TI  - Milk-flow data collected routinely in an automatic milking system: an alternative
      to milking-time testing in the management of teat-end condition?
AB  - BACKGROUND: Having a poor teat-end condition is associated with increased
      mastitis risk, hence avoiding milking machine settings that have a negative
      effect on teat-end condition is important for successful dairy production.
      Milking-time testing (MTT) can be used in the evaluation of vacuum conditions
      during milking, but the method is less suited for herds using automatic milking
      systems (AMS) and relationships with teat end condition is poorly described. This
      study aimed to increase knowledge on interpretation of MTT in AMS and to assess
      whether milk-flow data obtained routinely by an AMS can be useful for the
      management of teat-end health. A cross-sectional study, including 251 teats of 79
      Norwegian Red cows milked by AMS was performed in the research herd of the
      Norwegian University of Life Sciences. The following MTT variables were obtained
      at teat level: Average vacuum level in the short milk tube during main milking
      (MTVAC), average vacuum in the mouthpiece chamber during main milking and
      overmilking, teat compression intensity (COMPR) and overmilking time. Average and
      peak milk flow rates were obtained at quarter level from the AMS software. Teat
      end callosity thickness and roughness was registered, and teat dimensions;
      length, and width at apex and base, were measured. Interrelationships among
      variables obtained by MTT, quarter milk flow variables, and teat dimensions were
      described. Associations between these variables and teat-end callosity thickness
      and roughness, were investigated. RESULTS: Principal component analysis showed
      clusters of strongly related variables. There was a strong negative relationship
      between MTVAC and average milk flow rate. The variables MTVAC, COMPR and average
      and peak milk flow rate were associated with both thickness and roughness of the
      callosity ring. CONCLUSIONS: Quarter milk flow rate obtained directly from the
      AMS software was useful in assessing associations between milking machine
      function and teat-end condition; low average milk flow rates were associated with
      a higher likelihood of the teat having a thickened or roughened teat-end
      callosity ring. Since information on milk flow rate is readily available from the
      herd management system, this information might be used when evaluating causes for
      impaired teat-end condition in AMS.

PMID- 29325589
TI  - Catastrophic total costs in tuberculosis-affected households and their
      determinants since Indonesia's implementation of universal health coverage.
AB  - BACKGROUND: As well as imposing an economic burden on affected households, the
      high costs related to tuberculosis (TB) can create access and adherence barriers.
      This highlights the particular urgency of achieving one of the End TB Strategy's
      targets: that no TB-affected households have to face catastrophic costs by 2020.
      In Indonesia, as elsewhere, there is also an emerging need to provide social
      protection by implementing universal health coverage (UHC). We therefore assessed
      the incidence of catastrophic total costs due to TB, and their determinants since
      the implementation of UHC. METHODS: We interviewed adult TB and multidrug
      resistant TB (MDR-TB) patients in urban, suburban and rural areas of Indonesia
      who had been treated for at least one month or had finished treatment no more
      than one month earlier. Following the WHO recommendation, we assessed the
      incidence of catastrophic total costs due to TB. We also analyzed the sensitivity
      of incidence relative to several thresholds, and measured differences between
      poor and non-poor households in the incidence of catastrophic costs. Generalized
      linear mixed-model analysis was used to identify determinants of the catastrophic
      total costs. RESULTS: We analyzed 282 TB and 64 MDR-TB patients. For TB-related
      services, the median (interquartile range) of total costs incurred by households
      was 133 USD (55-576); for MDR-TB-related services, it was 2804 USD (1008-4325).
      The incidence of catastrophic total costs in all TB-affected households was 36%
      (43% in poor households and 25% in non-poor households). For MDR-TB-affected
      households, the incidence was 83% (83% and 83%). In TB-affected households, the
      determinants of catastrophic total costs were poor households (adjusted odds
      ratio [aOR] = 3.7, 95% confidence interval [CI]: 1.7-7.8); being a breadwinner
      (aOR = 2.9, 95% CI: 1.3-6.6); job loss (aOR = 21.2; 95% CI: 8.3-53.9); and
      previous TB treatment (aOR = 2.9; 95% CI: 1.4-6.1). In MDR-TB-affected
      households, having an income-earning job before diagnosis was the only
      determinant of catastrophic total costs (aOR = 8.7; 95% CI: 1.8-41.7).
      CONCLUSIONS: Despite the implementation of UHC, TB-affected households still risk
      catastrophic total costs and further impoverishment. As well as ensuring access
      to healthcare, a cost-mitigation policy and additional financial protection
      should be provided to protect the poor and relieve income losses.

PMID- 29325591
TI  - Correction to: Rp58 and p27kip1 coordinate cell cycle exit and neuronal migration
      within the embryonic mouse cerebral cortex.
AB  - CORRECTION: After publication of the original article [1] it was realised that
      there were errors in figures 2a,b,f,g, which arose as a result of preparing
      figures from data collected and analysed at the same time as the work reported in
      [2] (Supplementary Figure 1 of [2]). An updated Fig. 2 is included with this
      Correction.

PMID- 29325590
TI  - Dynamic changes in 18F-borono-L-phenylalanine uptake in unresectable, advanced,
      or recurrent squamous cell carcinoma of the head and neck and malignant melanoma
      during boron neutron capture therapy patient selection.
AB  - BACKGROUND: We evaluated dynamic changes in 18F-borono-L-phenylalanine (18F-BPA)
      uptake in unresectable, advanced, or recurrent squamous cell carcinoma of the
      head and neck (SCC) and malignant melanoma (MM) during boron neutron capture
      therapy (BNCT) patient selection. METHODS: Dynamic changes in the maximum
      standardized uptake value (SUVmax), tumor-to-normal tissue ratio (TNR), and tumor
      to-blood pool ratio (TBR) for 18F-BPA were evaluated in 20 patients with SCC and
      8 patients with MM. RESULTS: SUVmax in SCC tumors decreased significantly from 30
      to 120 min. There was a non-statistically significant decrease in SUVmax for SCC
      tumors from 30 to 60 min and from 60 to 120 min. Patients with MM had
      nonsignificant SUVmax changes in 18F-BPA uptake on delayed imaging.
      Nonsignificant 18F-BPA TNR and TBR changes were seen in patients with SCC and MM.
      CONCLUSIONS: Dynamic changes in SUVmax for 18F-BPA uptake had a washout pattern
      in SCC and a persistent pattern in MM. Dynamic 18F-BPA -PET studies should be
      performed to investigate the pharmacokinetics of 18F-BPA in humans and select
      appropriate candidates who may benefit from BNCT.

PMID- 29325593
TI  - Evaluating the long-term impact of the Fostering Changes training programme for
      foster carers in Wales, the Confidence in Care trial: study protocol for a
      randomised controlled trial.
AB  - BACKGROUND: The Fostering Changes programme was developed by the Adoption and
      Fostering National Team at the Maudsley Hospital, South London, in conjunction
      with King's College London. It is a 12-week group-based training programme for
      foster and kin carers, which aims to build positive relationships between carers
      and children, encourage positive child behaviour and set appropriate limits,
      through a practical skills-based approach. The programme also aims to improve
      foster carers' understanding of the causes of children's social and emotional
      difficulties and their confidence in applying this knowledge in various
      situations. METHODS: This is a pragmatic open-label individually randomised
      controlled trial, with embedded process evaluation. A total of 237 participants
      will be recruited from Welsh Local Authorities and Independent Fostering
      Providers; those allocated to the intervention group will be offered enrolment in
      the next Fostering Changes programme group at their site. Participants in the
      control group will be offered the Fostering Changes programme at the end of the
      follow-up period. Data will be collected at baseline, immediately following the
      12 week Fostering Changes intervention, and 12 months from the start of the
      Fostering Changes programme. The primary outcome measure assesses the extent to
      which carers feel able to cope with and make positive changes to the lives of
      their foster children and is measured by the Carer Efficacy Questionnaire at 12
      months. DISCUSSION: The trial will determine whether the Fostering Changes
      programme, in the long term, can deliver important, significant differences to
      the way foster carers build positive relationships with their foster children,
      encourage positive child behaviour and set appropriate limits, compared with
      usual care. TRIAL REGISTRATION: International Standard Randomised Controlled
      Trial Number, ISRCTN19090228 . Registered on 11 January 2017.

PMID- 29325592
TI  - MAGnesium sulphate for fetal neuroprotection to prevent Cerebral Palsy (MAG-CP)
      implementation of a national guideline in Canada.
AB  - BACKGROUND: Evidence supports magnesium sulphate (MgSO4) for women at risk of
      imminent birth at < 32-34 weeks to reduce the likelihood of cerebral palsy in the
      child. MAGnesium sulphate for fetal neuroprotection to prevent Cerebral Palsy
      (MAG-CP) was a multifaceted knowledge translation (KT) strategy for this
      practice. METHODS: The KT strategy included national clinical practice
      guidelines, a national online e-learning module and, at MAG-CP sites, educational
      rounds, focus group discussions and surveys of barriers and facilitators.
      Participating sites contributed data on pregnancies with threatened very preterm
      birth. In an interrupted time-series study design, MgSO4 use for fetal
      neuroprotection (NP) was tracked prior to (Aug 2005-May 2011) and during (Jun
      2011-Sept 2015) the KT intervention. Effectiveness of the strategy was measured
      by optimal MgSO4 use (i.e. administration when and only when indicated) over
      time, evaluated by a segmented generalised estimating equations logistic
      regression (p < 0.05 significant). Secondary outcomes included maternal effects
      and, using the Canadian Neonatal Network (CNN) database, national trends in MgSO4
      use for fetal NP and associated neonatal resuscitation. With an anticipated
      recruitment of 3752 mothers over 4 years at Canadian Perinatal Network sites, we
      anticipated > 95% power to detect an increase in optimal MgSO4 use for fetal NP
      from < 5 to 80% (2-sided, alpha 0.05) and at least 80% power to detect any
      increases observed in maternal side effects from RCTs. RESULTS: Seven thousand
      eight hundred eighty-eight women with imminent preterm birth were eligible for
      MgSO4 for fetal NP: 4745 pre-KT (18 centres) and 3143 during KT (11 centres). The
      KT intervention was associated with an 84% increase in the odds of optimal use
      (OR 1.00 to 1.84, p < 0.001), a reduction in the odds of underuse (OR 1.00 to
      0.47, p < 0.001) and an increase in suboptimal use (too early or at >= 32 weeks;
      OR 1.18 to 2.18, p < 0.001) of MgSO4 for fetal NP. Maternal hypotension was
      uncommon (7/1512, 0.5%). Nationally, intensive neonatal resuscitation decreased
      (p = 0.024) despite rising MgSO4 use for fetal NP (p < 0.001). CONCLUSION:
      Multifaceted KT was associated with significant increases in use of MgSO4 for
      fetal NP, with neither important maternal nor neonatal risks.

PMID- 29325594
TI  - Treatment of persistent allergic rhinitis via acupuncture at the sphenopalatine
      acupoint: a randomized controlled trial.
AB  - BACKGROUND: Allergic rhinitis is a common respiratory disease. Acupuncture is
      used to treat it in traditional Chinese medicine, and generally, the L120, ST2
      and ST36 acupoints are selected in clinical practice. We report a new method of
      acupuncture at the sphenopalatine acupoint (SPA) for treatment of persistent
      allergic rhinitis (PAR). The effect of this treatment was investigated using two
      different needling depths. The efficacy of this treatment was associated with
      accurate stimulation of the sphenopalatine ganglion (SPG). METHODS/DESIGN: A
      total of 61 patients diagnosed with PAR were randomly allocated to either the
      acupuncture or the sham acupuncture group. The difference between the groups was
      the needle depth when acupuncture was administered, which was 50 mm and 20 mm.
      Alteration in total nasal symptom score (TNSS) was the primary outcome. Quality
      of life, medication dosages and adverse events were secondary outcomes, measured
      using the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ). Confidence
      assessment was performed to evaluate data from the treatment and follow-up
      periods. RESULTS: Results were: (1) average TNSS in the treatment group was
      significantly lower than in the control group at week 4 (median and 25th and 75th
      percentiles were 5.00 (4.00, 7.00) and 8.00 (7.00, 10.00), respectively (P <
      0.001)). However, scores in the two groups were not significantly different at
      week 12; (2) quality of life (RQLQ) was significantly improved at week 2 in the
      treatment group compared to the control group (scores of 35.47 +/- 8.20 and 45.48
      +/- 8.84; P < 0.001); (3) during the follow-up period, the medication dosage in
      the treatment group was much lower than in the control group (3.64 +/- 1.45 and
      6.14 +/- 2.34; P < 0.05); and (4) no adverse events were observed in either group
      during treatment. CONCLUSIONS: This pilot study revealed a profound effect of
      acupuncture at the SPA on prevention of PAR development. The TNSS in the
      treatment group (needle depth 50 mm), was significantly lower than in the control
      group (needle depth of only 20 mm). Our result demonstrates that performing
      acupuncture directly at the SPA to stimulate the SPG is an effective method to
      treat PAR. TRIAL REGISTRATION: Acupuncture Clinical Trial Registry, AMCTR-OOR
      16000014 and Chinese Clinical Trial Register, ChiCTR-IOR-16009211 . Registered on
      1 September 1 2016.

PMID- 29325595
TI  - Mortality impact of an increased blood glucose cut-off level for hypoglycaemia
      treatment in severely sick children in Malawi (SugarFACT trial): study protocol
      for a randomised controlled trial.
AB  - BACKGROUND: Mortality in children remains high in sub-Saharan African hospitals.
      While antimalarial drugs, antibiotics and other definitive treatments are well
      understood, the role of emergency care with supportive therapies, such as
      maintaining normal glucose and electrolyte balances, has been given limited
      attention. Hypoglycaemia is common in children admitted to hospital in low-income
      settings. The current definition of hypoglycaemia is a blood glucose level < 2.5
      mmol/L in a well-nourished child. Outcomes for these children are poor, with a
      mortality rate of up to 42%. An increased mortality has also been reported among
      acutely ill children with low-glycaemia, defined as a blood glucose level of 2.5
      5.0 mmol/L. The reason for increased mortality rates is not fully understood.
      This proposal is for a randomised controlled trial to determine the impact on
      mortality of a raised treatment cut-off level for paediatric hypoglycaemia.
      METHODS: A total of 1266 severely ill children (age range = 1 month - 5 years)
      admitted to Queen Elizabeth Central Hospital in Blantyre, Malawi with blood
      glucose in the range of 2.5-5.0 mmol/L will be randomised into intervention or
      control groups. The intervention group will be treated with an intravenous bolus
      of 10% dextrose 5 mL/kg followed by a dextrose infusion in addition to standard
      care while the control group will receive standard care only. Children will be
      followed until discharge from hospital or death. DISCUSSION: The first patient
      was enrolled in December 2016 and the expected trial deadline is January 2019.
      This study is the first to evaluate the benefits of increased dextrose
      administration in children presenting to hospital with low-glycaemia. The
      findings will inform national and international policies and guidelines for the
      management of children with blood sugar abnormalities. TRIAL REGISTRATION:
      ClinicalTrials.gov, NCT02989675 . Registered on 5 December 2016.

PMID- 29325596
TI  - Late normal tissue response in the rat spinal cord after carbon ion irradiation.
AB  - BACKGROUND: The present work summarizes the research activities on radiation
      induced late effects in the rat spinal cord carried out within the "clinical
      research group ion beam therapy" funded by the German Research Foundation (DFG,
      KFO 214). METHODS AND MATERIALS: Dose-response curves for the endpoint radiation
      induced myelopathy were determined at 6 different positions (LET 16-99 keV/MUm)
      within a 6 cm spread-out Bragg peak using either 1, 2 or 6 fractions of carbon
      ions. Based on the tolerance dose TD50 of carbon ions and photons, the relative
      biological effectiveness (RBE) was determined and compared with predictions of
      the local effect model (LEM I and IV). Within a longitudinal magnetic resonance
      imaging (MRI)-based study the temporal development of radiation-induced changes
      in the spinal cord was characterized. To test the protective potential of the ACE
      (angiotensin converting enzyme)-inhibitor ramiprilTM, an additional dose-response
      experiment was performed. RESULTS: The RBE-values increased with LET and the
      increase was found to be larger for smaller fractional doses. Benchmarking the
      RBE-values as predicted by LEM I and LEM IV with the measured data revealed that
      LEM IV is more accurate in the high-LET, while LEM I is more accurate in the low
      LET region. Characterization of the temporal development of radiation-induced
      changes with MRI demonstrated a shorter latency time for carbon ions, reflected
      on the histological level by an increased vessel perforation after carbon ion as
      compared to photon irradiations. For the ACE-inhibitor ramiprilTM, a mitigative
      rather than protective effect was found. CONCLUSIONS: This comprehensive study
      established a large and consistent RBE data base for late effects in the rat
      spinal cord after carbon ion irradiation which will be further extended in
      ongoing studies. Using MRI, an extensive characterization of the temporal
      development of radiation-induced alterations was obtained. The reduced latency
      time for carbon ions is expected to originate from a dynamic interaction of
      various complex pathological processes. A dominant observation after carbon ion
      irradiation was an increase in vessel perforation preferentially in the white
      matter. To enable a targeted pharmacological intervention more details of the
      molecular pathways, responsible for the development of radiation-induced
      myelopathy are required.

PMID- 29325597
TI  - Disseminated histoplasmosis in an immunocompetent patient - utility of skin
      scrape cytology in diagnosis: a case report.
AB  - BACKGROUND: Histoplasma capsulatum is a dimorphic fungus predominately found in
      soils enriched with bird and bat excreta. Although several cases of
      histoplasmosis have been reported in India, diagnosis using cytology has been
      done in very few cases. CASE PRESENTATION: We report here a case of disseminated
      histoplasmosis in a 46-year-old Indian man. CONCLUSION: Skin scrape cytology is a
      simple, safe, and rapid technique to establish the initial diagnosis, thus
      promoting early treatment and favorable outcome, in cutaneous fungal infections.

PMID- 29325598
TI  - Influence of peer review on the reporting of primary outcome(s) and statistical
      analyses of randomised trials.
AB  - BACKGROUND: Selective reporting of outcomes in clinical trials is a serious
      problem. We aimed to investigate the influence of the peer review process within
      biomedical journals on reporting of primary outcome(s) and statistical analyses
      within reports of randomised trials. METHODS: Each month, PubMed (May 2014 to
      April 2015) was searched to identify primary reports of randomised trials
      published in six high-impact general and 12 high-impact specialty journals. The
      corresponding author of each trial was invited to complete an online survey
      asking authors about changes made to their manuscript as part of the peer review
      process. Our main outcomes were to assess: (1) the nature and extent of changes
      as part of the peer review process, in relation to reporting of the primary
      outcome(s) and/or primary statistical analysis; (2) how often authors followed
      these requests; and (3) whether this was related to specific journal or trial
      characteristics. RESULTS: Of 893 corresponding authors who were invited to take
      part in the online survey 258 (29%) responded. The majority of trials were
      multicentre (n = 191; 74%); median sample size 325 (IQR 138 to 1010). The primary
      outcome was clearly defined in 92% (n = 238), of which the direction of treatment
      effect was statistically significant in 49%. The majority responded (1-10 Likert
      scale) they were satisfied with the overall handling (mean 8.6, SD 1.5) and
      quality of peer review (mean 8.5, SD 1.5) of their manuscript. Only 3% (n = 8)
      said that the editor or peer reviewers had asked them to change or clarify the
      trial's primary outcome. However, 27% (n = 69) reported they were asked to change
      or clarify the statistical analysis of the primary outcome; most had fulfilled
      the request, the main motivation being to improve the statistical methods (n =
      38; 55%) or avoid rejection (n = 30; 44%). Overall, there was little association
      between authors being asked to make this change and the type of journal,
      intervention, significance of the primary outcome, or funding source. Thirty-six
      percent (n = 94) of authors had been asked to include additional analyses that
      had not been included in the original manuscript; in 77% (n = 72) these were not
      pre-specified in the protocol. Twenty-three percent (n = 60) had been asked to
      modify their overall conclusion, usually (n = 53; 88%) to provide a more cautious
      conclusion. CONCLUSION: Overall, most changes, as a result of the peer review
      process, resulted in improvements to the published manuscript; there was little
      evidence of a negative impact in terms of post hoc changes of the primary
      outcome. However, some suggested changes might be considered inappropriate, such
      as unplanned additional analyses, and should be discouraged.

PMID- 29325599
TI  - Are we there yet? An update on transitional care in rheumatology.
AB  - Significant progress has been made in the understanding of transitional care in
      rheumatology over the last few decades, yet universal implementation has not been
      realised and unmet needs continue to be reported. Possible explanations for this
      include lack of evidence as to which model is most effective; lack of attention
      to the multiple dimensions, stakeholders and systems involved in health
      transitions; and lack of consideration of the developmental appropriateness of
      transition interventions and the services/organisations/systems where such
      interventions are delivered.Successful transition has major implications to both
      the young people with juvenile-onset rheumatic disease and their families. Future
      research in this area will need to reflect both the multidimensional
      (biopsychosocial) and the multisystemic (multiple systems and stakeholders across
      personal/social/family support networks and health/social care/education
      systems). Only then will we be able to determine which aspects of transition
      readiness and service components influence which dimension. It is therefore
      imperative we continue to research and develop this area, involving both
      paediatric and adult rheumatology clinicians and researchers, remembering to look
      beyond both the condition and our discipline. Neither should we forget to tap
      into the exciting potential associated with digital technology to ensure further
      advances in transitional care are brought about in and beyond rheumatology.

PMID- 29325600
TI  - Clival Chordoma With Brainstem Invasion.

PMID- 29325601
TI  - Evaluation of ELISA and haemagglutination inhibition as screening tests in
      serosurveillance for H5/H7 avian influenza in commercial chicken flocks.
AB  - Avian influenza virus (AIV) subtypes H5 and H7 can infect poultry causing low
      pathogenicity (LP) AI, but these LPAIVs may mutate to highly pathogenic AIV in
      chickens or turkeys causing high mortality, hence H5/H7 subtypes demand statutory
      intervention. Serological surveillance in the European Union provides evidence of
      H5/H7 AIV exposure in apparently healthy poultry. To identify the most sensitive
      screening method as the first step in an algorithm to provide evidence of H5/H7
      AIV infection, the standard approach of H5/H7 antibody testing by
      haemagglutination inhibition (HI) was compared with an ELISA, which detects
      antibodies to all subtypes. Sera (n = 1055) from 74 commercial chicken flocks
      were tested by both methods. A Bayesian approach served to estimate diagnostic
      test sensitivities and specificities, without assuming any 'gold standard'.
      Sensitivity and specificity of the ELISA was 97% and 99.8%, and for H5/H7 HI 43%
      and 99.8%, respectively, although H5/H7 HI sensitivity varied considerably
      between infected flocks. ELISA therefore provides superior sensitivity for the
      screening of chicken flocks as part of an algorithm, which subsequently utilises
      H5/H7 HI to identify infection by these two subtypes. With the calculated
      sensitivity and specificity, testing nine sera per flock is sufficient to detect
      a flock seroprevalence of 30% with 95% probability.

PMID- 29325603
TI  - Culture conditions affect Ca2+ release in artificially activated mouse and human
      oocytes.
AB  - Inconsistent fertilisation and pregnancy rates have been reported by different
      laboratories after application of ionomycin as a clinical method of assisted
      oocyte activation (AOA) to overcome fertilisation failure. Using both mouse and
      human oocytes, in the present study we investigated the effects of ionomycin and
      Ca2+ concentrations on the pattern of Ca2+ release and embryonic developmental
      potential. In the mouse, application of 5MUM ionomycin in potassium simplex
      optimisation medium (KSOM) or 10uM ionomycin in Ca2+-free KSOM significantly
      reduced the Ca2+ flux and resulted in failure of blastocyst formation compared
      with 10MUM ionomycin in KSOM. Increasing the Ca2+ concentration up to three- or
      sixfold did not benefit mouse embryonic developmental potential. Similarly, 10MUM
      ionomycin-induced rise in Ca2+ in human oocytes increased with increasing total
      calcium concentrations in the commercial medium. Remarkably, we observed
      significantly reduced mouse embryo development when performing AOA over a period
      of 10min in Quinn's AdvantageTM Fertilisation medium (Cooper Surgical) and IVFTM
      medium (Vitrolife) compared with Sydney IVF COOK cleavage medium (Cook Ireland),
      using the same sequential culture system from the post-activation stage to
      blastocyst formation stage in different AOA groups. In conclusion, concentrations
      of both ionomycin and Ca2+ in culture media used during AOA can have significant
      effects on Ca2+ release and further embryonic developmental potential.

PMID- 29325604
TI  - Implications of body condition and seasonality on morphological and functional
      parameters of testes of Myotis nigricans (Chiroptera: Vespertilionidae).
AB  - The insectivorous bat Myotis nigricans is widely distributed throughout the
      Neotropics, including Brazil, and has a reproductive biology that is affected by
      climate and food availability. To evaluate the reproductive capacity of this
      species, morphofunctional parameters of the testes were correlated with
      environmental variables and the body condition of individuals captured. After
      bats had been killed, their testes were removed, fixed in Karnovsky's fluid for
      24h and embedded in resin for evaluation by light microscopy. The mean annual
      tubulosomatic index (0.58%) and the percentage of seminiferous tubules in the
      testes (88.96%) were the highest ever recorded for the Order Chiroptera. The
      percentage of Leydig cells and volume of the cytoplasm of Leydig cells were
      higher in the rainy than dry season (80.62+/-3.19% and 573.57+/-166.95MUm,
      respectively; mean+/-s.d.). Conversely, the percentage of nuclei of the Leydig
      cells in the dry season (26.17+/-3.70%; mean+/-s.d.) and the total number of
      Leydig cells (6.38+/-1.84*109; mean+/-s.d.) were higher in the dry season. The
      results of the present study could help in future conservation of these bats
      because they provide a better understanding of the bats' reproductive strategies
      and how the species can adapt to changes.

PMID- 29325605
TI  - Establishment of detection antibodies BRRs batch 4 for in vitro potency assay of
      hepatitis A vaccines by ELISA.
AB  - The European Pharmacopoeia (Ph. Eur.) standard ELISA method for determination of
      antigen content of hepatitis A vaccines (HAV) requires specific coating and
      detection Biological Reference Reagents (BRRs). The 3rd batch of detection
      antibodies BRRs was established in 2015 for use in conjunction with the Ph. Eur.
      general chapter 2.7.14 'Assay of hepatitis A vaccine'. Stocks of these BRRs were
      running low and therefore the European Directorate for the Quality of Medicines &
      HealthCare (EDQM) organised a collaborative study to qualify replacement batches.
      The candidate BRR antibodies batch 4 were prepared under appropriate conditions
      from starting materials similar to previous batches to ensure continuity. During
      the collaborative study, the new batches of antibodies were compared to previous
      batches of BRRs. Results confirmed that they were suitable to be used for the
      intended purpose, and could be used at the same final concentrations as the
      previous batch, i.e. 1:500 for the primary antibody and 1:400 for the conjugated
      secondary antibody. They were adopted in June 2017 by the Ph. Eur. Commission as
      Hepatitis A virus primary detection antibody BRR batch 4 and Conjugated secondary
      detection antibody BRR batch 4, respectively. They are available from the EDQM as
      Hepatitis A vaccine ELISA detection antibodies set BRR batch 4.

PMID- 29325606
TI  - Repeat expansion diseases.
AB  - More than 40 diseases, most of which primarily affect the nervous system, are
      caused by expansions of simple sequence repeats dispersed throughout the human
      genome. Expanded trinucleotide repeat diseases were discovered first and remain
      the most frequent. More recently tetra-, penta-, hexa-, and even dodeca
      nucleotide repeat expansions have been identified as the cause of human disease,
      including some of the most common genetic disorders seen by neurologists. Repeat
      expansion diseases include both causes of myotonic dystrophy (DM1 and DM2), the
      most common genetic cause of amyotrophic lateral sclerosis/frontotemporal
      dementia (C9ORF72), Huntington disease, and eight other polyglutamine disorders,
      including the most common forms of dominantly inherited ataxia, the most common
      recessive ataxia (Friedreich ataxia), and the most common heritable mental
      retardation (fragile X syndrome). Here I review distinctive features of this
      group of diseases that stem from the unusual, dynamic nature of the underlying
      mutations. These features include marked clinical heterogeneity and the
      phenomenon of clinical anticipation. I then discuss the diverse molecular
      mechanisms driving disease pathogenesis, which vary depending on the repeat
      sequence, size, and location within the disease gene, and whether the repeat is
      translated into protein. I conclude with a brief clinical and genetic description
      of individual repeat expansion diseases that are most relevant to neurologists.

PMID- 29325607
TI  - Genetic and genomic testing for neurologic disease in clinical practice.
AB  - The influence of genetics on neurologic disease is broad and it is becoming more
      common that clinicians are presented with a patient whose disease is likely of
      genetic origin. In the search for mutations causing Mendelian disorders, advances
      in genetic testing methodology have propelled modern neurologic practice beyond
      single-gene testing into the realm of genomic medicine, where routine evaluations
      encompass hundreds or thousands of genes, or even the entire exome, representing
      all protein-coding genes in the genome. The role of various single-gene,
      multigene, and genomic testing methods, including chromosomal microarray and next
      generation sequencing, in the evaluation of neurologic disease is discussed here
      to provide a framework for their use in a modern neurologic practice.
      Understanding the inherent issues that arise during the interpretation of
      sequence variants as pathogenic or benign and the potential discovery of
      incidental medically relevant findings are important considerations for
      neurologists utilizing these tests clinically. Strategies for the evaluation of
      clinically heterogeneous disorders are presented to guide neurologists in the
      transition from single-gene to genomic considerations and toward the prospect of
      the widespread routine use of exome sequencing in the continuing goal to achieve
      more rapid and more precise diagnoses that will improve management and outcome in
      patients challenged by neurologic disease.

PMID- 29325602
TI  - Bile Acid Metabolism in Liver Pathobiology.
AB  - Bile acids facilitate intestinal nutrient absorption and biliary cholesterol
      secretion to maintain bile acid homeostasis, which is essential for protecting
      liver and other tissues and cells from cholesterol and bile acid toxicity. Bile
      acid metabolism is tightly regulated by bile acid synthesis in the liver and bile
      acid biotransformation in the intestine. Bile acids are endogenous ligands that
      activate a complex network of nuclear receptor farnesoid X receptor and membrane
      G protein-coupled bile acid receptor-1 to regulate hepatic lipid and glucose
      metabolic homeostasis and energy metabolism. The gut-to-liver axis plays a
      critical role in the regulation of enterohepatic circulation of bile acids, bile
      acid pool size, and bile acid composition. Bile acids control gut bacteria
      overgrowth, and gut bacteria metabolize bile acids to regulate host metabolism.
      Alteration of bile acid metabolism by high-fat diets, sleep disruption, alcohol,
      and drugs reshapes gut microbiome and causes dysbiosis, obesity, and metabolic
      disorders. Gender differences in bile acid metabolism, FXR signaling, and gut
      microbiota have been linked to higher prevalence of fatty liver disease and
      hepatocellular carcinoma in males. Alteration of bile acid homeostasis
      contributes to cholestatic liver diseases, inflammatory diseases in the digestive
      system, obesity, and diabetes. Bile acid-activated receptors are potential
      therapeutic targets for developing drugs to treat metabolic disorders.

PMID- 29325608
TI  - Mitochondrial diseases.
AB  - Mitochondrial diseases collectively describe a diverse group of heritable
      disorders that invariably affect mitochondrial respiratory chain function and
      cellular energy production. Together they represent the most common cause of
      inherited metabolic disease, may present at any age, have a wide spectrum of
      clinical manifestations, may be insidious in onset, and potentially have high
      morbidity and mortality. Due to the presence of mitochondria in all nucleated
      cells, mitochondrial disease can affect many different tissues, with single or
      multiple systems being involved. This leads to highly variable presentations,
      making the diagnosis of mitochondrial diseases challenging. Recent advances in
      biomarker and genetic testing, coupled with emerging treatments and reproductive
      options, hold great promise for improving the clinical identification and
      management of this highly mutable disease group.

PMID- 29325609
TI  - The CAG-polyglutamine repeat diseases: a clinical, molecular, genetic, and
      pathophysiologic nosology.
AB  - Throughout the genome, unstable tandem nucleotide repeats can expand to cause a
      variety of neurologic disorders. Expansion of a CAG triplet repeat within a
      coding exon gives rise to an elongated polyglutamine (polyQ) tract in the
      resultant protein product, and accounts for a unique category of
      neurodegenerative disorders, known as the CAG-polyglutamine repeat diseases. The
      nine members of the CAG-polyglutamine disease family include spinal and bulbar
      muscular atrophy (SBMA), Huntington disease, dentatorubral pallidoluysian
      atrophy, and six spinocerebellar ataxias (SCA 1, 2, 3, 6, 7, and 17). All CAG
      polyglutamine diseases are dominantly inherited, with the exception of SBMA,
      which is X-linked, and many CAG-polyglutamine diseases display anticipation,
      which is defined as increasing disease severity in successive generations of an
      affected kindred. Despite widespread expression of the different polyQ-expanded
      disease proteins throughout the body, each CAG-polyglutamine disease strikes a
      particular subset of neurons, although the mechanism for this cell-type
      selectivity remains poorly understood. While the different genes implicated in
      these disorders display amino acid homology only in the repeat tract domain,
      certain pathologic molecular processes have been implicated in almost all of the
      CAG-polyglutamine repeat diseases, including protein aggregation, proteolytic
      cleavage, transcription dysregulation, autophagy impairment, and mitochondrial
      dysfunction. Here we highlight the clinical and molecular genetic features of
      each distinct disorder, and then discuss common themes in CAG-polyglutamine
      disease pathogenesis, closing with emerging advances in therapy development.

PMID- 29325611
TI  - Autosomal-recessive cerebellar ataxias.
AB  - The autosomal-recessive cerebellar ataxias comprise more than half of the known
      genetic forms of ataxia and represent an extensive group of clinically
      heterogeneous disorders that can occur at any age but whose onset is typically
      prior to adulthood. In addition to ataxia, patients often present with
      polyneuropathy and clinical symptoms outside the nervous system. The most common
      of these diseases is Friedreich ataxia, caused by mutation of the frataxin gene,
      but recent advances in genetic analysis have greatly broadened the ever-expanding
      number of causative genes to over 50. In this review, the clinical neurogenetics
      of the recessive cerebellar ataxias will be discussed, including updates on
      recently identified novel ataxia genes, advancements in unraveling disease
      specific molecular pathogenesis leading to ataxia, potential treatments under
      development, technologic improvements in diagnostic testing such as clinical
      exome sequencing, and what the future holds for clinicians and geneticists.

PMID- 29325610
TI  - Autosomal-dominant cerebellar ataxias.
AB  - Spinocerebellar ataxias (SCAs) are a genetically diverse group of dominantly
      inherited disorders that share clinical features that result from dysfunction and
      degeneration of the cerebellum and its associated pathways. Although nearly 40
      genes are currently recognized to result in SCA, shared mechanisms for disease
      pathogenesis exist among subsets of the SCAs. The most common SCAs result from a
      glutamine-encoding CAG repeat in the respective disease genes. This chapter
      discusses the varied genetic etiology of SCA and attempts to categorize these
      disorders based on shared mechanisms of disease. We also summarize evaluation and
      management for the SCAs.

PMID- 29325612
TI  - Genetics of Parkinson disease.
AB  - An understanding of the genetic etiology of Parkinson disease (PD) has become
      imperative for the modern-day neurologist. Although genetic forms cause only a
      minority of PD, the disease mechanisms they elucidate advance the understanding
      of idiopathic cases. Moreover, recently identified susceptibility variants
      contribute to complex-etiology PD and broaden the contribution of genetics beyond
      familial and early-onset cases. Dominantly inherited monogenic forms mimic
      idiopathic PD and are caused by mutations or copy number variations of SNCA,
      LRRK2, and VPS35. On the other hand, early-onset forms are associated with
      PARKIN, PINK1, and DJ1 mutations, nominating mitochondrial dysfunction and
      oxidative stress as another important molecular pathway in the causation of the
      disease, in addition to alpha-synuclein accumulation. Common variants in GBA are
      consistently identified by association studies and may be considered to be a
      major risk gene for PD, with markedly reduced penetrance. Other genes have been
      proposed to be associated with PD; however, these only cause very rare forms, if
      at all. Current guidelines recommend testing for LRRK2 variants in familial PD or
      in specific populations (ancestry), and for the recessive genes in early-onset
      PD. However, gene panels have made testing for multiple forms of genetic PD a
      viable approach.

PMID- 29325615
TI  - Inherited dystonias: clinical features and molecular pathways.
AB  - Recent decades have witnessed dramatic increases in understanding of the genetics
      of dystonia - a movement disorder characterized by involuntary twisting and
      abnormal posture. Hampered by a lack of overt neuropathology, researchers are
      investigating isolated monogenic causes to pinpoint common molecular mechanisms
      in this heterogeneous disease. Evidence from imaging, cellular, and murine work
      implicates deficiencies in dopamine neurotransmission, transcriptional
      dysregulation, and selective vulnerability of distinct neuronal populations to
      disease mutations. Studies of genetic forms of dystonia are also illuminating the
      developmental dependence of disease symptoms that is typical of many forms of the
      disease. As understanding of monogenic forms of dystonia grows, a clearer picture
      will develop of the abnormal motor circuitry behind this relatively common
      phenomenology. This chapter focuses on the current data covering the etiology and
      epidemiology, clinical presentation, and pathogenesis of four monogenic forms of
      isolated dystonia: DYT-TOR1A, DYT-THAP1, DYT-GCH1, and DYT-GNAL.

PMID- 29325616
TI  - Huntington disease.
AB  - Huntington disease is a monogenic neurodegenerative disorder that displays an
      autosomal-dominant pattern of inheritance. It is characterized by motor,
      psychiatric, and cognitive symptoms that progress over 15-20 years. Since the
      identification of the causative genetic mutation in 1993 much has been discovered
      about the underlying pathogenic mechanisms, but as yet there are no disease
      modifying therapies available. This chapter reviews the epidemiology, genetic
      basis, pathogenesis, presentation, and clinical management of Huntington disease.
      The principles of genetic testing are explained. We also describe recent
      developments in the ongoing search for therapeutics and for biomarkers to track
      disease progression.

PMID- 29325614
TI  - Ethical issues in neurogenetics.
AB  - Many neurogenetic conditions are inherited and therefore diagnosis of a patient
      will have implications for the patient's relatives and can raise ethical issues.
      Predictive genetic testing offers asymptomatic relatives the opportunity to
      determine their risk status for a neurogenetic condition, and professional
      guidelines emphasize patients' autonomy and informed, voluntary decision making.
      Beneficence and nonmaleficence both need to be considered when making decisions
      about disclosure and nondisclosure of genetic information and test results. There
      can be disclosure concerns and challenges in determining whose autonomy to
      prioritize when a patient makes a genetic testing decision that can reveal the
      genetic status of a relative (e.g., testing an adult child when the at-risk
      parent has not been tested). Ethical issues are prominent when genetic testing
      for neurogenetic conditions is requested prenatally, on minors, adoptees, adult
      children at 25% risk, and for individuals with psychiatric issues or cognitive
      impairment. Neurogenetic conditions can result in cognitive decline which can
      affect decisional capacity and lead to ethical challenges with decision making,
      informed consent, and determining the patient's ability to comprehend test
      results. The ethical implications of genetic testing and emerging issues,
      including direct-to-consumer genetic testing, disclosure of secondary findings
      from genomic sequencing, and use of apolipoprotein E testing in clinical and
      research settings, are also discussed. Resources for information about genetic
      testing practice guidelines, insurance laws, and directories of genetics clinics
      are included.

PMID- 29325613
TI  - Essential tremor.
AB  - Essential tremor (ET) is one of the most common neurologic disorders, and genetic
      factors are thought to contribute significantly to disease etiology. There has
      been a relative lack of progress in understanding the genetic etiology of ET.
      This could reflect a number of factors, including the presence of substantial
      phenotypic and genotypic heterogeneity. Thus, a meticulous approach to
      phenotyping is important for genetic research. A lack of standardized phenotyping
      across studies and patient centers likely has contributed to the relative lack of
      success of genomewide association studies in ET. To dissect the genetic
      architecture of ET, whole-genome sequencing will likely be of value. This will
      allow specific hypotheses about the mode of inheritance and genetic architecture
      to be tested. A number of approaches still remain unexplored in ET genetics,
      including the contribution of copy number variants, uncommon moderate-effect
      alleles, rare variant large-effect alleles (including Mendelian and
      complex/polygenic modes of inheritance), de novo and gonadal mosaicism,
      epigenetic changes, and noncoding variation.

PMID- 29325617
TI  - Wilson disease and related copper disorders.
AB  - Copper is a required cofactor for enzymes in critical metabolic pathways.
      Mutations in copper metabolism genes or abnormalities in copper metabolism result
      in disease from copper excess or deficiency. Wilson disease (WD) is an autosomal
      recessive disease caused by mutations in the ATP7B gene which encodes a copper
      transporting ATPase. Over 500 different WD mutations throughout the ATP7B gene
      have been described, most of which are missense mutations. Mutations in both
      ATP7B alleles result in abnormal copper metabolism and subsequent toxic
      accumulation of copper. The clinical manifestations of neurologic WD include
      variable combinations of dysarthria, dystonia, tremor, and choreoathetosis.
      Misdiagnosis and delay in treatment are clinically relevant because untreated WD
      progresses to hepatic failure or severe neurologic disability and death.
      Treatment can prevent and cure WD. Mutations in a second, closely related copper
      transporting ATPase, ATP7A, cause a spectrum of copper deficiency disorders that
      include Menkes disease, occipital horn syndrome, and ATP7A-related distal motor
      neuropathy. Two important, nongenetic causes of copper deficiency myeloneuropathy
      are copper deficiency following gastric bypass or due to excess zinc ingestion,
      both of which can cause a myeloneuropathy similar to vitamin B12 deficiency.
      Copper deficiency following gastric bypass is preventable, and identification and
      elimination of the excess zinc source, most commonly dental cream, can result in
      recovery.

PMID- 29325618
TI  - Neurodegeneration with brain iron accumulation.
AB  - Neurodegeneration with brain iron accumulation (NBIA) comprises a clinically and
      genetically heterogeneous group of disorders affecting children and adults. These
      rare disorders are often first suspected when increased basal ganglia iron is
      observed on brain magnetic resonance imaging. For the majority of NBIA disorders
      the genetic basis has been delineated, and clinical testing is available. The
      four most common NBIA disorders include pantothenate kinase-associated
      neurodegeneration (PKAN) due to mutations in PANK2, phospholipase A2-associated
      neurodegeneration caused by mutation in PLA2G6, mitochondrial membrane protein
      associated neurodegeneration from mutations in C19orf12, and beta-propeller
      protein-associated neurodegeneration due to mutations in WDR45. The ultrarare
      NBIA disorders are caused by mutations in CoASY, ATP13A2, and FA2H (causing CoA
      synthase protein-associated neurodegeneration, Kufor-Rakeb disease, and fatty
      acid hydroxylase-associated neurodegeneration, respectively). Together, these
      genes account for disease in approximately 85% of patients diagnosed with an NBIA
      disorder. New NBIA genes are being recognized with increasing frequency as a
      result of whole-exome sequencing, which is also facilitating early ascertainment
      of patients whose phenotype is often nonspecific.

PMID- 29325619
TI  - Clinical approach to the patient with neurogenetic disease.
AB  - Neurogenetic diseases are surprisingly common. This chapter reviews a systematic
      approach to the evaluation of a patient thought to have such a disease. The
      emphasis is on first recognizing potential clues to the diagnosis contained in
      the family history and presentation of symptoms. Ataxia, neuropathy, muscle
      weakness, dementia, epilepsy, and cognitive delay are all "reservoirs" of
      neurogenetic disease. A high index of suspicion for genetic causes and a
      thoughtful evaluation of simplex (sporadic) cases is often necessary. Then the
      physician can proceed to the differential diagnosis, genetic testing, and genetic
      counseling. A team approach including a genetic counselor is usually the best
      strategy.

PMID- 29325620
TI  - Primary familial brain calcifications.
AB  - Primary familial brain calcification (PFBC) is a neurodegenerative disease with
      characteristic calcium deposits in the basal ganglia and other brain regions. The
      disease usually presents as a combination of abnormal movements, cognitive and
      psychiatric manifestations, clinically indistinguishable from other adult-onset
      neurodegenerative disorders. The differential diagnosis must be established with
      genetic and nongenetic disorders that can also lead to calcium deposits in
      encephalic structures. In the past years PFBC causal mutations have been
      discovered in genes related to calcium phosphate homeostasis (SLC20A2, XPR1) and
      in genes involved with endothelial function and integrity (PDGFB, PDGFRB). The
      most frequently mutated gene is SLC20A2, where mutations can affect any domain of
      the protein. There is no clearcut relationship between the specific
      mutation/gene, onset age, neuroimaging pattern, and severity of clinical
      manifestations. The discovery of the genetic basis of PFBC provides not only a
      diagnostic tool, but also an insight into the pathomechanisms and potential
      therapeutic trials for this rare disease.

PMID- 29325621
TI  - Genetics of autism spectrum disorder.
AB  - Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder
      characterized by impaired social interaction and stereotyped behaviors. ASD has a
      strong and complex genetic component, with multiple familial inheritance patterns
      and an estimate of up to 1000 genes potentially implicated. Over the past decade,
      genomic technologies have enabled rapid progress in the identification of risk
      genes for ASD. In this chapter, we review the delineation of ASD disease genes
      starting from traditional genetic studies such as linkage and association, and
      then focusing on more recent studies utilizing genomic technologies, such as high
      throughput genotyping and exome sequencing.

PMID- 29325622
TI  - The emerging genetic landscape of cerebral palsy.
AB  - Cerebral palsy (CP) is a broad clinical descriptor that encompasses a
      heterogeneous group of nonprogressive neurodevelopmental disabilities affecting
      movement and posture. While linked by the presence of damage to the developing
      brain, the etiology of CP is likely varied and the clinical outcomes are diverse.
      There is now a large body of evidence supporting a significant role for genetics
      in causation of CP. An increasing number of studies have identified likely
      causative genetic variants in families with CP, as well as in individual sporadic
      cases. Next-generation sequencing is now aiding clinicians in making specific
      molecular diagnoses, providing future opportunities for tailored treatments and
      for informed reproductive decisions.

PMID- 29325623
TI  - Tourette disorder and other tic disorders.
AB  - Tourette disorder is a developmental neuropsychiatric condition characterized by
      vocal and motor tics that can range in severity from mild to disabling. It
      represents one end of a spectrum of tic disorders and is estimated to affect 0.5
      0.7% of the population. Accumulated evidence supports a substantial genetic
      contribution to disease risk, but the identification of genetic variants that
      confer risk has been challenging. Positive findings in candidate gene association
      studies have not replicated, and genomewide association studies have not
      generated signals of genomewide significance, in large part because of inadequate
      sample sizes. Rare mutations in several genes have been identified, but their
      causality is difficult to establish. As in other complex neuropsychiatric
      disorders, it is likely that Tourette disorder risk involves a combination of
      common, low-effect and rare, larger-effect variants in multiple genes acting
      together with environmental factors. With the ongoing collection of larger
      patient cohorts and the emergence of affordable high-throughput genomewide
      sequencing, progress is expected to accelerate in coming years.

PMID- 29325624
TI  - Sex chromosome aneuploidies.
AB  - Sex chromosome aneuploidies comprise a relatively common group of chromosome
      disorders characterized by the loss or gain of one or more sex chromosomes. We
      discuss five of the better-known sex aneuploidies: Turner syndrome (XO),
      Klinefelter syndrome (XXY), trisomy X (XXX), XYY, and XXYY. Despite their
      prevalence in the general population, these disorders are underdiagnosed and the
      specific genetic mechanisms underlying their phenotypes are poorly understood.
      Although there is considerable variation between them in terms of associated
      functional impairment, each disorder has a characteristic physical, cognitive,
      and neurologic profile. The most common cause of sex chromosome aneuploidies is
      nondisjunction, which can occur during meiosis or during the early stages of
      postzygotic development. The loss or gain of genetic material can affect all
      daughter cells or it may be partial, leading to tissue mosaicism. In both typical
      and atypical sex chromosome karyotypes, there is random inactivation of all but
      one X chromosome. The mechanisms by which a phenotype results from sex chromosome
      aneuploidies are twofold: dosage imbalance arising from a small number of genes
      that escape inactivation, and their endocrinologic consequences.

PMID- 29325625
TI  - Evolving views of human genetic variation and its relationship to neurologic and
      psychiatric disease.
AB  - Recent advances in exome and genome sequencing in populations are beginning to
      define the genetic architecture of neurologic and psychiatric disease. At the
      same time these findings are changing our perspective of genetic variant
      contributions to disease, implicating both rare and common genetic variation in
      common diseases. Most of what we know about genetic contributions to disease so
      far comes from analysis of mutations in protein-coding genes. Since most genetic
      variation lies in nonprotein-coding regions of the genome whose presumed function
      is entirely regulatory, understanding gene regulation in a cell type and
      developmental state-specific manner will be important to connect human genetic
      variation to disease mechanisms.

PMID- 29325626
TI  - Fragile X syndrome and fragile X-associated tremor ataxia syndrome.
AB  - Fragile X-associated disorders encompass several conditions, which are caused by
      expansion mutations in the fragile X mental retardation 1 (FMR1) gene. Fragile X
      syndrome is the most common inherited etiology of intellectual disability and
      results from a full mutation or >200 CGG repeats in FMR1. It is associated with
      developmental delay, autism spectrum disorder, and seizures. Fragile X-associated
      tremor/ataxia syndrome is a progressive neurodegenerative disease that occurs in
      premutation carriers of 55-200 CGG repeats in FMR1 and is characterized by
      kinetic tremor, gait ataxia, parkinsonism, executive dysfunction, and neuropathy.
      Fragile X-associated primary ovarian insufficiency also occurs in premutation
      carrier women and manifests with infertility and early menopause. The diseases
      constituting fragile X-associated disorders differ mechanistically, due to the
      distinct molecular properties of premutation versus full mutations. Fragile X
      syndrome occurs when there is a lack of fragile X mental retardation protein
      (FMRP) due to FMR1 methylation and silencing. In fragile X-associated tremor
      ataxia syndrome, a toxic gain of function is postulated with the production of
      excess CGG repeat-containing FMR1 mRNA, abnormal translation of the repeat
      sequence leading to production of polyglycine, polyalanine, and other
      polypeptides and to outright deficits in translation leading to reduced FMRP at
      larger premutation sizes. The changes in underlying brain chemistry due to FMR1
      mutations have led to therapeutic studies in these disorders, with some progress
      being made in fragile X syndrome. This paper also summarizes indications for
      testing, genetic counseling issues, and what the future holds for these
      disorders.

PMID- 29325627
TI  - Epigenetic mechanisms underlying nervous system diseases.
AB  - Epigenetic mechanisms act as control systems for modulating genomic structure and
      activity in response to evolving profiles of cell-extrinsic, cell-cell, and cell
      intrinsic signals. These dynamic processes are responsible for mediating cell-
      and tissue-specific gene expression and function and gene-gene and gene
      environmental interactions. The major epigenetic mechanisms include DNA
      methylation and hydroxymethylation; histone protein posttranslational
      modifications, nucleosome remodeling/repositioning, and higher-order chromatin
      reorganization; noncoding RNA regulation; and RNA editing. These mechanisms are
      intimately involved in executing fundamental genomic programs, including gene
      transcription, posttranscriptional RNA processing and transport, translation, X
      chromosome inactivation, genomic imprinting, retrotransposon regulation, DNA
      replication, and DNA repair and the maintenance of genomic stability. For the
      nervous system, epigenetics offers a novel and robust framework for explaining
      how brain development and aging occur, neural cellular diversity is generated,
      synaptic and neural network connectivity and plasticity are mediated, and complex
      cognitive and behavioral phenotypes are inherited transgenerationally. Epigenetic
      factors and processes are, not surprisingly, implicated in nervous system disease
      pathophysiology through several emerging paradigms - mutations and genetic
      variation in genes encoding epigenetic factors; impairments in epigenetic factor
      expression, localization, and function; epigenetic mechanisms modulating disease
      associated factors and pathways; and the presence of deregulated epigenetic
      profiles in central and peripheral tissues.

PMID- 29325628
TI  - Pharmacogenetics.
AB  - Pharmacogenetics is the study of how genetics influences drug treatment outcomes.
      Much research has been conducted to identify and characterize gene variants that
      impact the pharmacokinetic and pharmacodynamic aspects of medications used to
      treat neurologic and psychiatric disorders. This chapter reviews the current
      state of pharmacogenetic aspects of these treatments. Medications with supporting
      pharmacogenetic information in product labeling, clinical guidelines, or
      important mechanistic implications are discussed. At this time, clinically
      relevant genetic variation in drug metabolizing enzymes may inform drug dosing
      for a number of medications metabolized in the liver. Additionally, genetic
      variation in immunological genes may be tested to assess risk for severe
      hypersensitivity reactions to some anticonvulsant drugs. Finally, a growing body
      of research highlights that genetic polymorphisms in drug targets may influence
      symptom response or tolerability to some treatments.

PMID- 29325630
TI  - Towards precision medicine.
AB  - The concept of precision medicine, also referred to as individualized or
      personalized medicine, has recently gained traction in scientific, medical, and
      public spheres, and is frequently mentioned as the next model of healthcare
      delivery. Its goal is to integrate unique information obtained from a given
      patient to customize the care provided to achieve the best possible outcome.
      Although precision medicine is not fully implemented yet, its application is
      slowly infiltrating clinical practice, and the dream of individualizing
      healthcare to each patient is now closer to being fulfilled. This chapter
      summarizes the current status of personalized medicine in the neurology clinic,
      including precision diagnostics and individualized therapeutics. Subsequently, we
      address the main hurdles that the healthcare community needs to overcome to
      expand this model of healthcare delivery and predict how this evolving field will
      shape future neurologic practice.

PMID- 29325629
TI  - Bioinformatics and genomic databases.
AB  - High-throughput, low-cost sequencing technologies have begun to yield new
      insights into biology and medicine. New data enable the interrogation of the
      molecular biology of disease from DNA to RNA to protein, charting the central
      dogma. This chapter reviews some of the key advances and resources in the
      application of bioinformatics to understanding, and ultimately diagnosing and
      treating, diseases of the nervous system. Array genotyping, exome sequencing, and
      whole-genome sequencing, in both disease and healthy populations, have enabled
      the interpretation of new genetic data. Profiling of epigenetic markers, such as
      histone modifications, has added to our understanding of the regulatory machinery
      of the genome. Downstream, mRNA, and protein expression data from published
      experiments and high-throughput studies enable complex analyses of gene function
      across many experimental conditions and tissues. Further delineation of molecular
      mechanism arises from the concept of genes working together in pathways or
      networks, reflecting direct protein interactions and regulatory relationships.
      The rapidly moving field of bioinformatics has made significant contributions to
      neurology in these early days; continued advances promise to transform medicine
      from basic science to clinical practice, as more genomics data are generated,
      combined, and analyzed in the future.

PMID- 29325631
TI  - Preface.

PMID- 29325632
TI  - Foreword.

PMID- 29325633
TI  - Lowering the Thresholds of Diseases: Is Anyone Still Healthy?

PMID- 29325634
TI  - Relationship of Aging and Incident Comorbidities to Stroke Risk in Patients With
      Atrial Fibrillation.
AB  - BACKGROUND: When assessing ischemic stroke risk in patients with atrial
      fibrillation (AF), the CHA2DS2-VASc score is calculated based on the baseline
      risk factors, and the outcomes are determined after a follow-up period. However,
      the stroke risk in patients with AF does not remain static, and with time,
      patients get older and accumulate more comorbidities. OBJECTIVES: This study
      hypothesized that the "Delta CHA2DS2-VASc score," which reflects the change in
      score between baseline and follow-up, would be more predictive of ischemic stroke
      compared with the baseline CHA2DS2-VASc score. METHODS: A total of 31,039
      patients with AF who did not receive antiplatelet agents or oral anticoagulants,
      and who did not have comorbidities of the CHA2DS2-VASc score except for age and
      sex, were studied. The Delta CHA2DS2-VASc scores were defined as the differences
      between the baseline and follow-up CHA2DS2-VASc scores. During 171,956 person
      years, 4,103 patients experienced ischemic stroke. The accuracies of baseline,
      follow-up, and Delta CHA2DS2-VASc scores in predicting ischemic stroke were
      analyzed and compared. RESULTS: The mean baseline CHA2DS2-VASc score was 1.29,
      which increased to 2.31 during the follow-up, with a mean Delta CHA2DS2-VASc
      score of 1.02. The CHA2DS2-VASc score remained unchanged in only 40.8% of
      patients. Among 4,103 patients who experienced ischemic stroke, 89.4% had a Delta
      CHA2DS2-VASc score >=1 compared with only 54.6% in patients without ischemic
      stroke, and 2,643 (64.4%) patients had >=1 new-onset comorbidity, the most common
      being hypertension. The Delta CHA2DS2-VASc score was a significant predictor of
      ischemic stroke that performed better than baseline or follow-up CHA2DS2-VASc
      scores, as assessed by the C-index and the net reclassification index.
      CONCLUSIONS: In this AF cohort, the authors demonstrated that the CHA2DS2-VASc
      score was not static, and that most patients with AF developed >=1 new stroke
      risk factor before presentation with ischemic stroke. The Delta CHA2DS2-VASc
      score, reflecting the change in score between baseline and follow-up, was
      strongly predictive of ischemic stroke, reflecting how stroke risk in AF is a
      dynamic process due to increasing age and incident comorbidities.

PMID- 29325635
TI  - Stroke Prediction Rules in Atrial Fibrillation.

PMID- 29325636
TI  - Left Atrial Appendage Closure and Systemic Homeostasis: The LAA HOMEOSTASIS
      Study.
AB  - BACKGROUND: The impact of left atrial appendage (LAA) exclusion, comparing an
      epicardial LAA or an endocardial LAA device, on systemic homeostasis remains
      unknown. OBJECTIVES: This study compared the effects of epicardial or endocardial
      LAA devices on the neurohormonal profiles of patients, emphasizing the roles of
      the renin-angiotensin-aldosterone system and the autonomic nervous system.
      METHODS: This is a prospective, single-center, observational study including 77
      patients who underwent LAA closure by an epicardial (n = 38) or endocardial (n =
      39) device. Key hormones involved in the adrenergic system (adrenaline,
      noradrenaline), renin-angiotensin-aldosterone system (aldosterone, renin),
      metabolic system (adiponectin, free fatty acids, insulin, beta-hydroxybutyrate,
      and free glycerols), and natriuresis (atrial and B-type natriuretic peptides)
      were assessed immediately before the procedure, immediately after device
      deployment, at 24 h, and at 3 months follow-up. RESULTS: In the endocardial LAA
      device group, when compared with baseline blood adrenaline, noradrenaline and
      aldosterone were significantly lower at 24 h and 3 months (p < 0.05). There was
      no significant change in levels post-endocardial LAA device implantation. After
      epicardial LAA device implantation, there were significant increases in
      adiponectin and insulin, with decreased free fatty acids at 3 months. There was
      no significant change in these levels post-endocardial LAA device. N-terminal pro
      A-type natriuretic peptide and N-terminal pro-B-type natriuretic peptide were
      significantly decreased in the acute phase after epicardial LAA device
      implantation, which subsequently normalized at 3 months. Post endocardial LAA
      device implantation, the levels increased immediately and normalized after 24 h.
      Systemic blood pressure was also significantly lower at all time points after
      epicardial LAA device implantation, which was not seen post-endocardial LAA
      device implantation. CONCLUSIONS: There are substantial differences in
      hemodynamics and neurohormonal effects of LAA exclusion with epicardial and
      endocardial devices. Further studies are required to elucidate the underlying
      mechanism of these physiological changes.

PMID- 29325637
TI  - Neurohormonal Regulation and the Left Atrial Appendage: Still More to Learn.

PMID- 29325638
TI  - Implantable Cardioverter-Defibrillators in Children and Adolescents With Brugada
      Syndrome.
AB  - BACKGROUND: Young patients presenting with symptomatic Brugada syndrome have very
      high risks for ventricular arrhythmias and should be carefully considered for
      implantable cardioverter-defibrillator (ICD) placement. However, this therapy is
      associated with high rates of inappropriate shocks and device-related
      complications. OBJECTIVES: This study investigated clinical features, management,
      and long-term follow-up of young patients with Brugada syndrome and ICD. METHODS:
      Patients diagnosed with Brugada syndrome, who underwent implantation of an ICD at
      an age of <=20 years, were studied. RESULTS: The study included 35 consecutive
      patients. The mean age at ICD placement was 13.9 +/- 6.2 years. Ninety-two
      percent were symptomatic; 29% presented with aborted sudden cardiac death and 63%
      with syncope. During a mean follow-up period of 88 months, sustained ventricular
      arrhythmias were treated by the ICD in 9 patients (26%), including shocks in 8
      patients (23%) and antitachycardia pacing in 1 patient (3%). Three patients (9%)
      died in an electrical storm. Seven patients (20%) experienced inappropriate
      shocks, and 5 patients (14%) had device-related complications. Aborted sudden
      cardiac death and spontaneous type I electrocardiogram were identified as
      independent predictors of appropriate shock occurrence. CONCLUSIONS: ICD therapy
      is an effective strategy in young patients with symptomatic Brugada syndrome,
      treating potentially lethal arrhythmias in >25% of patients during follow-up.
      Appropriate shocks were significantly associated with previously aborted sudden
      cardiac death and spontaneous type I electrocardiograms. However, ICDs are
      frequently associated with complications and inappropriate shocks, both of which
      remain high regardless of careful device implantation and programming.

PMID- 29325639
TI  - Pediatric Brugada Syndrome: Avoiding the Inappropriate ICD.

PMID- 29325640
TI  - Selective EGF-Receptor Inhibition in CD4+ T Cells Induces Anergy and Limits
      Atherosclerosis.
AB  - BACKGROUND: Several epidermal growth factor receptor (EGFR) inhibitors have been
      successfully developed for the treatment of cancer, limiting tumor growth and
      metastasis. EGFR is also expressed by leukocytes, but little is known about its
      role in the modulation of the immune response. OBJECTIVES: The aim of this study
      was to determine whether EGFR expressed on CD4+ T cells is functional and to
      address the consequences of EGFR inhibition in atherosclerosis, a T cell-mediated
      vascular chronic inflammatory disease. METHODS: The authors used EGFR tyrosine
      kinase inhibitors (AG-1478, erlotinib) and chimeric Ldlr-/-Cd4-Cre/Egfrlox/lox
      mouse with a specific deletion of EGFR in CD4+ T cells. RESULTS: Mouse CD4+ T
      cells expressed EGFR, and the EGFR tyrosine kinase inhibitor AG-1478 blocked in
      vitro T cell proliferation and Th1/Th2 cytokine production. In vivo, treatment of
      Ldlr-/- mice with the EGFR inhibitor erlotinib induced T cell anergy, reduced T
      cell infiltration within atherosclerotic lesions, and protected against
      atherosclerosis development and progression. Selective deletion of EGFR in CD4+ T
      cells resulted in decreased T cell proliferation and activation both in vitro and
      in vivo, as well as reduced interferon-gamma, interleukin-4, and interleukin-2
      production. Atherosclerotic lesion size was reduced by 2-fold in irradiated Ldlr
      /- mice reconstituted with bone marrow from Cd4-Cre/Egfrlox/lox mice, compared to
      Cd4-Cre/Egfr+/+ chimeric mice, after 4, 6, and 12 weeks of high-fat diet,
      associated with marked reduction in T cell infiltration in atherosclerotic
      plaques. Human blood T cells expressed EGFR and EGFR inhibition reduced T cell
      proliferation both in vitro and in vivo. CONCLUSIONS: EGFR blockade induced T
      cell anergy in vitro and in vivo and reduced atherosclerosis development.
      Targeting EGFR may be a novel strategy to combat atherosclerosis.

PMID- 29325641
TI  - Taming Immune and Inflammatory Responses to Treat Atherosclerosis.

PMID- 29325644
TI  - Direct Oral Anticoagulants and Risk of Acute Kidney Injury in Patients With
      Atrial Fibrillation.

PMID- 29325643
TI  - The Secret Life of Exosomes: What Bees Can Teach Us About Next-Generation
      Therapeutics.
AB  - Mechanistic exploration has pinpointed nanosized extracellular vesicles, known as
      exosomes, as key mediators of the benefits of cell therapy. Exosomes appear to
      recapitulate the benefits of cells and more. As durable azoic entities, exosomes
      have numerous practical and conceptual advantages over cells. Will cells end up
      just being used to manufacture exosomes, or will they find lasting value as
      primary therapeutic agents? Here, a venerable natural process-the generation of
      honey-serves as an instructive parable. Flowers make nectar, which bees collect
      and process into honey. Cells make conditioned medium, which laboratory workers
      collect and process into exosomes. Unlike flowers, honey is durable, compact, and
      nutritious, but these facts do not negate the value of flowers themselves. The
      parallels suggest new ways of thinking about next-generation therapeutics.

PMID- 29325645
TI  - Persistent Survival Benefit From Remote Ischemic Pre-Conditioning in Patients
      Undergoing Coronary Artery Bypass Surgery.

PMID- 29325646
TI  - Functional Contribution of Circumferential Versus Longitudinal Strain: Different
      Concepts Suggest Conflicting Results.

PMID- 29325642
TI  - NHLBI Working Group Recommendations to Reduce Lipoprotein(a)-Mediated Risk of
      Cardiovascular Disease and Aortic Stenosis.
AB  - Pathophysiological, epidemiological, and genetic studies provide strong evidence
      that lipoprotein(a) [Lp(a)] is a causal mediator of cardiovascular disease (CVD)
      and calcific aortic valve disease (CAVD). Specific therapies to address Lp(a)
      mediated CVD and CAVD are in clinical development. Due to knowledge gaps, the
      National Heart, Lung, and Blood Institute organized a working group that
      identified challenges in fully understanding the role of Lp(a) in CVD/CAVD. These
      included the lack of research funding, inadequate experimental models, lack of
      globally standardized Lp(a) assays, and inadequate understanding of the
      mechanisms underlying current drug therapies on Lp(a) levels. Specific
      recommendations were provided to facilitate basic, mechanistic, preclinical, and
      clinical research on Lp(a); foster collaborative research and resource sharing;
      leverage expertise of different groups and centers with complementary skills; and
      use existing National Heart, Lung, and Blood Institute resources. Concerted
      efforts to understand Lp(a) pathophysiology, together with diagnostic and
      therapeutic advances, are required to reduce Lp(a)-mediated risk of CVD and CAVD.

PMID- 29325647
TI  - Myocardial Contraction Fraction: A Volumetric Measure of Myocardial Shortening
      Analogous to Strain.

PMID- 29325648
TI  - Complexities in Modeling the Relationship Between Longitudinal Strain and
      Ejection Fraction.

PMID- 29325649
TI  - Reply: Interaction Between Longitudinal, Circumferential, and Radial Deformations
      and Their Contributions to Ejection Fraction.

PMID- 29325650
TI  - Arterial Thromboembolism in Non-Hodgkin Lymphoma.

PMID- 29325651
TI  - Recurrent Late Bioresorbable Scaffold Thrombosis as a Presenting Symptom of
      Underlying Cancer.

PMID- 29325652
TI  - Risk of Arterial Thrombosis in Cancer Patients: Which Role for Cancer Therapies
      Vascular Toxicities?

PMID- 29325654
TI  - Celebrating JNEB's 50th volume.

PMID- 29325655
TI  - A Comment on Mann G "Smart Snacks in School Legislation Does Not Change Self
      Reported Snack Food and Beverage Intake of Middle School Students in Rural
      Appalachian Region": Methodological Issues.

PMID- 29325653
TI  - Reply: Arterial Thromboembolism in Non-Hodgkin Lymphoma, as the Presentation of
      Occult Cancer, and With Cancer Therapies.

PMID- 29325656
TI  - Response to "A Comment on Mann G 'Smart Snacks in School Legislation Does Not
      Change Self-Reported Snack Food and Beverage Intake of Middle School Students in
      Rural Appalachian Region': Methodological Issues".

PMID- 29325657
TI  - My Quest, an Intervention Using Text Messaging to Improve Dietary and Physical
      Activity Behaviors and Promote Weight Loss in Low-Income Women.
AB  - OBJECTIVE: To evaluate changes in dietary and physical activity behaviors and
      weight after implementation of a 12-week text messaging initiative (My Quest).
      DESIGN: The researchers conducted a 1-group, pre- to posttest study design to
      determine changes after implementation of a text messaging initiative developed
      using the tenets of the Social Cognitive Theory. SETTING: A total of 55 Alabama
      counties (84% rural) with high rates of poverty, overweight/obesity, and chronic
      diseases. PARTICIPANTS: Convenience sample of low-income, primarily
      overweight/obese women (n = 104). INTERVENTION: Short texts (n = 2-3/d) provided
      health tips, reminders, and goal-setting prompts. Weekly electronic newsletters
      provided tips and recipes. Participant self-monitored body weight weekly. MAIN
      OUTCOME MEASURE: Outcomes included goal setting, self-efficacy, behavioral and
      environmental factors, self-monitoring, and body weight; data collection occurred
      through text message response and online surveys. ANALYSIS: Analyses were
      conducted using McNemar test (dichotomous data), Wilcoxon signed rank test
      (ordinal data), or paired t test (continuous data). RESULTS: Participants
      significantly (P < .05) improved dietary and physical activity behaviors and food
      environment; increased dietary and physical activity goal setting; and reduced
      body weight. CONCLUSIONS AND IMPLICATIONS: A low-cost, text messaging initiative
      particularly targeting women residing in rural communities with high rates of
      poverty and obesity can promote weight loss and improve dietary and physical
      activity behaviors. Future studies may include a control group and social support
      component such as group text messaging.

PMID- 29325658
TI  - Tele-Motivational Interviewing for Cancer Survivors: Feasibility, Preliminary
      Efficacy, and Lessons Learned.
AB  - OBJECTIVE: Determine the feasibility, acceptability, and efficacy of tele
      Motivational Interviewing (MI) for overweight cancer survivors. DESIGN: Six-month
      nonrandomized phase 2 clinical trial. SETTING: Urban garden and remote platforms.
      PARTICIPANTS: Overweight and obese cancer survivors post active treatment.
      INTERVENTION: Remote tele-MI from a trained registered dietitian nutritionist
      (RDN). MAIN OUTCOME MEASURES: Feasibility, acceptability, and preliminary
      efficacy. ANALYSIS: Groups were stratified as users and nonusers based on tele-MI
      use. Qualitative survey data and remote MI interaction logs were analyzed for
      trends. Two-sample t tests were performed to assess pre-post intervention changes
      in physical activity and dietary behaviors, quality of life, self-efficacy, and
      clinical biomarkers. RESULTS: A total of 29 participants completed the
      intervention. There were 17 tele-MI users (59%) and 12 nonusers (41%). Users were
      primarily female (88%), breast cancer survivors (59%), college educated (82%),
      with a mean age of 58 years. Users set 50% more goals, lost more weight (4.8 vs
      2.6 kg), significantly improved quality of life (P = .03), and trended more
      positively in clinical biomarkers (eg, cholesterol, blood pressure) than did
      nonusers. CONCLUSIONS AND IMPLICATIONS: Findings from this study indicate that
      tele-MI is a feasible and acceptable intervention for overweight cancer survivors
      after active therapy. Larger randomized trials are needed to establish efficacy
      and generalizability to a variety of demographic populations.

PMID- 29325659
TI  - Technology and JNEB's Birthday.

PMID- 29325660
TI  - Impact of the Lactation Advice Through Texting Can Help (LATCH) Trial on Time to
      First Contact and Exclusive Breastfeeding among WIC Participants.
AB  - OBJECTIVE: Determine the impact of a 2-way text messaging intervention on time to
      contact between participants and their breastfeeding peer counselors (BFPCs) and
      on exclusive breastfeeding (EBF) status at 2 weeks and 3 months postpartum.
      DESIGN: Multisite, single-blind, randomized, controlled trial. SETTING: Special
      Supplemental Nutrition Program for Women, Infants, and Children (WIC) BFPC
      program. PARTICIPANTS: Low-income women (n = 174) participating in the WIC BFPC
      program. INTERVENTION: The control group received the standard of care WIC Loving
      Support BFPC program. The intervention group received standard of care plus the
      text messaging intervention. MAIN OUTCOME MEASURES: Time to contact with BFPC and
      EBF status. ANALYSIS: The 2-sample t test or chi2 test assessed whether an
      association existed between study variables and each outcome. Multivariable
      ordinal and binary logistic regression assessed the impact of the intervention on
      time to contact and EBF status. RESULTS: Lactation Advice Through Texting Can
      Help had a significant impact on early contact between participants and BFPCs
      (odds ratio = 2.93; 95% confidence interval, 1.35-6.37) but did not have a
      significant impact on EBF (odds ratio = 1.26; 95% confidence interval, 0.54
      2.66). CONCLUSIONS AND IMPLICATIONS: Lactation Advice Through Texting Can Help
      has the potential to facilitate the work of BFPCs by shortening the time-to-first
      contact with clients after giving birth. Research is needed to identify the level
      of breastfeeding support staff coverage that WIC clinics must have to meet the
      demand for services created by Lactation Advice Through Texting Can Help.

PMID- 29325661
TI  - Facebook: The Use of Social Media to Engage Parents in a Preschool Obesity
      Prevention Curriculum.
AB  - OBJECTIVE: This study investigated the use of Facebook to deliver health-related
      education materials to augment a preschool classroom-based obesity prevention
      curriculum. DESIGN: Cross-sectional, mixed methods (descriptive and interviews).
      SETTING: Head Start classrooms administered by 2 large agencies (1 rural and 1
      urban). PARTICIPANTS: Convenience sample of parents in 13 classrooms (cohort 1, 3
      classrooms; cohort 2, 10 classrooms). INTERVENTION: Delivery of nutrition
      education curriculum content using social media (Facebook). VARIABLES MEASURED:
      Qualitative interviews assessed barriers and facilitators to Facebook use. Parent
      views, likes, and comments were measured to reflect parent engagement with
      Facebook. ANALYSIS: Content analyses (qualitative data) and descriptive
      statistics (quantitative data). RESULTS: Family access (views) and interaction
      (comments and likes) with the posts varied based on type and content of posts.
      Rural families were more active. Barriers to parental Facebook engagement
      included a desire to see more posts from classroom teachers, lack of time, and
      misunderstanding about privacy protections. Facilitators of parental Facebook
      engagement included perceived utility of the content and social support.
      CONCLUSIONS AND IMPLICATIONS: Facebook was found to be a feasible platform to
      provide nutrition education and facilitated varying levels of parental
      engagement. Lessons learned and implications for prevention and intervention
      programming are offered.

PMID- 29325662
TI  - Farmers' Market Manager's Level of Communication and Influence on Electronic
      Benefits Transfer (EBT) Adoption at Midwest Farmers' Markets.
AB  - OBJECTIVE: To understand market managers' level of communication and use of
      technology that might influence decision to adopt Electronic Benefits Transfer
      (EBT) at farmers' markets. DESIGN: Cross-sectional study using the Theory of
      Diffusion of Innovation. SETTING: Electronic survey administered in midwest
      states of Illinois, Michigan, and Wisconsin. PARTICIPANTS: Farmers' market
      managers in Illinois, Michigan, and Wisconsin. MAIN OUTCOME MEASURES: Information
      on EBT adoption, market managers' communication, and technology use. ANALYSIS:
      Binary logistic regression analysis with EBT adoption as the dependent variable
      and frequency of technology use, partnership with organizations, farmers' market
      association (FMA) membership, Facebook page and Web site for the market, and
      primary source of information as independent variables. Chi-square tests and
      ANOVA were used to compare states and adopter categories. RESULTS: Logistic
      regression results showed that the odds of adopting EBT was 7.5 times higher for
      markets that had partnership with other organizations. Compared with non
      adopters, a significantly greater number of early adopters had partnership, FMA
      membership, and a Facebook page and Web site for market, and reported to a board
      of directors. CONCLUSIONS AND IMPLICATIONS: Markets that had partnership, FMA
      membership, a Facebook page and Web site, and mandatory reporting to a board of
      directors were important factors that influenced EBT adoption at midwest farmers'
      markets.

PMID- 29325663
TI  - Daily and Seasonal Influences on Dietary Self-monitoring Using a Smartphone
      Application.
AB  - OBJECTIVE: To examine within-person variation in dietary self-monitoring during a
      6-month technology-supported weight loss trial as a function of time-varying
      factors including time in the study, day of the week, and month of the year.
      METHODS: Smartphone self-monitoring data were examined from 31 obese adults (aged
      18-60 years) who participated in a 6-month technology-supported weight loss
      program. Multilevel regression modeling was used to examine within-person
      variation in dietary self-monitoring. RESULTS: Participants recorded less as time
      in the study progressed. Fewer foods were reported on the weekends compared with
      weekdays. More foods were self-monitored in January compared with October;
      however, a seasonal effect was not observed. CONCLUSIONS AND IMPLICATIONS: The
      amount of time in a study and day of the week were associated with dietary self
      monitoring but not season. Future studies should examine factors that influence
      variations in self-monitoring and identify methods to improve technology
      supported dietary self-monitoring adherence.

PMID- 29325664
TI  - Results of the Clinician Apps Survey, How Clinicians Working With Patients With
      Diabetes and Obesity Use Mobile Health Apps.
AB  - OBJECTIVE: To develop and administer a questionnaire to determine what factors
      may be associated with app use (including frequency of use, reasons to recommend
      to clients/patients, perceived effectiveness on health, health aspects used,
      features, and types of apps) by clinicians working in diabetes and weight
      management patient care settings. METHODS: The Clinician Apps Survey was
      developed and contained 3 question domains (smartphone apps use, behavior theory
      in counseling sessions, and demographics) to explore frequency, types, preferred
      features, benefits/barriers of using apps, counseling techniques used, and
      clinician demographics. Clinicians (n = 719) were recruited to complete the
      online survey through 4 dietetics and diabetes professional groups. Clinician use
      and preferences for health-related apps for personal reasons and in patient care
      settings were determined, and comparisons were made between high and non-app
      users. Descriptive statistics were used with current practices and attitudes
      about apps. Chi-square test of independence compared those using apps both
      personally and professionally (app enthusiasts) vs those with no app use.
      RESULTS: There were more app enthusiasts (53%; n = 380) than non-app users (20%;
      n = 145). Whereas 68% recommended pen/paper methods for diet and physical
      activity monitoring, 62% recommended apps. Most agreed that apps were superior to
      traditional methods for patients to track dietary intake (62%) and physical
      activity (58%), make better food choices (34%), lose weight (45%), and track
      blood glucose (43%). App enthusiasts used the American Association of Diabetes
      Educators self-care guidelines (P = .001) and advanced counseling techniques (eg,
      motivational interviewing) more often than did non-app users (P < .004). Apps
      most frequently recommended to clients were MyFitnessPal (n = 425), CalorieKing
      (n = 356), and Fitbit (n = 312). CONCLUSIONS AND IMPLICATIONS: Health-related
      smartphone apps are being widely used and recommended to patients with diabetes
      and obesity by clinicians for self-monitoring of dietary and physical activity
      behaviors. Furthermore, many clinicians believe that these types of tracking apps
      may improve patient outcomes compared with traditional methods of monitoring
      dietary and physical activity behaviors.

PMID- 29325666
TI  - Examining Internet Access and Social Media Application Use for Online Nutrition
      Education in SNAP-Ed Participants in Rural Illinois.
AB  - OBJECTIVE: To examine Internet access and interest in receiving nutrition
      education via social media applications among low-income adults participating in
      the Supplemental Nutrition Assistance Program Education (SNAP-Ed). METHODS: A
      cross-sectional survey was distributed during 25 SNAP-Ed classes throughout the
      16 southernmost counties of Illinois. RESULTS: From 188 responses, the majority
      of participants had Internet access (76%). Among participants aged 18-32 years (n
      = 51), 92% owned a smartphone with Internet access and 57% indicated that they
      would use online nutrition education, with most interest in e-mail (41%),
      Facebook (40%), and text messaging (35%). There was little interest in using
      blogs, Vine, Twitter, Tumblr, and Pinterest. Overall, 49% of middle-aged adults
      aged 33-64 years and 87% of seniors aged >=65 years reported they would not use
      online nutrition education. CONCLUSIONS AND IMPLICATIONS: Results indicated
      similar Internet accessibility in southern Illinois among low-income populations
      compared with national rural rates. Interest in using online nutrition education
      varied among SNAP-Ed participants according to age. Young adults appeared to be
      the most captive audience regarding online nutrition education. Results may be
      useful to agencies implementing SNAP-Ed to supplement current curriculum with
      online nutrition education for audiences aged <=32 years.

PMID- 29325667
TI  - Development of an Online Smartphone-Based eLearning Nutrition Education Program
      for Low-Income Individuals.
AB  - The objective of this report was to describe the development process of an
      innovative smartphone-based electronic learning (eLearning) nutrition education
      program targeted to Supplemental Nutrition Assistance Program-Education-eligible
      individuals, entitled Food eTalk. Lessons learned from the Food eTalk development
      process suggest that it is critical to include all key team members from the
      program's inception using effective inter-team communication systems, understand
      the unique resources needed, budget ample time for development, and employ an
      iterative development and evaluation model. These lessons have implications for
      researchers and funding agencies in developing an innovative evidence-based
      eLearning nutrition education program to an increasingly technology-savvy, low
      income audience.

PMID- 29325665
TI  - Feasibility and Acceptability of Delivering a Postpartum Weight Loss Intervention
      via Facebook: A Pilot Study.
AB  - OBJECTIVE: To evaluate the feasibility and acceptability of a Facebook-delivered
      postpartum weight loss intervention. METHODS: Overweight and obese postpartum
      women received a 12-week weight loss intervention via Facebook. Feasibility
      outcomes were recruitment, retention, engagement, and acceptability. Weight loss
      was an exploratory outcome. RESULTS: Participants (n = 19) were 3.5 (SD 2.2)
      months postpartum with a baseline body mass index of 30.1 (SD 4.2) kg/m2.
      Retention was 95%. Forty-two percent of participants visibly engaged on the last
      day of the intervention, and 100% in the last 4 weeks; 88% were likely or very
      likely to participate again and 82% were likely or very likely to recommend the
      program to a postpartum friend. Average 12-week weight loss was 4.8% (SD 4.2%);
      58% lost >=5%. CONCLUSIONS AND IMPLICATIONS: Findings suggested that this
      Facebook-delivered intervention is feasible and acceptable and supports research
      to test efficacy for weight loss. Research is needed to determine how best to
      engage participants in social network-delivered weight loss interventions.

PMID- 29325668
TI  - Increasing Sense of Community in Higher Education Nutrition Courses Using
      Technology.
AB  - Sense of community is integral across education formats and can affect
      achievement, interactivity, and retention. Factors shown to engage students and
      foster sense of community include the instructor focusing and directing
      discussions, encouraging open expression of opinions, responding to
      communications and feedback in a timely way, and giving the opportunity to build
      relationships. Technology has tremendous potential to enhance these activities at
      all levels of higher education. This article presents ways in which several
      technologies are used to enhance student experience in undergraduate and graduate
      nutrition course work across delivery formats.

PMID- 29325669
TI  - Kidney damage due to the use of anabolic androgenic steroides and practice of
      bodybuilding.

PMID- 29325670
TI  - Obesity and renal function. Data from the epidemiological study: Prevalence of
      chronic renal disease in Spain. EPIRCE Study.

PMID- 29325671
TI  - Evaluation of the dialyser inner diameter in online haemodiafiltration.
AB  - INTRODUCTION: Online haemodiafiltration (OL-HDF) has been associated with
      increased survival. To date, the influence of the inner diameter of the hollow
      fibres of the dialyser on convective volume has not been well established. The
      objective of the study was to evaluate the effect of increasing the inner
      diameter of the dialyser on the convective volume and removal capacity. MATERIAL
      AND METHODS: We included 16 patients in posdilutional OL-HDF with
      autosubstitution. Each patient was analysed in 4 sessions in which the inner
      diameter varied; 185MUm (FX60 Cordiax and FX80 Cordiax) versus 210MUm (FX600
      Cordiax and FX800 Cordiax). Different solutes were measured at the beginning and
      end of each dialysis session. RESULTS: No differences in the convective volume
      were found with an increased inner diameter: 32.3+/-3.1 vs. 31.8+/-3.6 l/session
      (FX60 vs. FX600) and 33.7+/-4.3 vs. 33.5+/-3.8 l/session (FX80 vs. FX800). The
      reduction percentages also did not differ: urea 83.7+/-4.5 vs. 84.1+/-3.4 for
      FX60 and FX600, and 82.7+/-4.1 vs. 83.6+/-3.8 for FX80 vs. FX800; creatinine
      similar 78.2+/-5.6 vs. 77.8+/-4.6 y 77.1+/-5.4 vs. 78.1+/-4.9; beta2
      microglobulin 82.2+/-4.3 vs. 82.9+/-4.2, and 82.9+/-4.7 vs. 84.0+/-3.8; myoglobin
      71.0+/-10 vs. 70.2+/-9 and 72.8+/-11 vs. 75.0+/-10; prolactin 70.4+/-9 vs. 68.1+/
      9, and 72.2+/-10 vs. 73.4+/-8.2; and alpha1-microglobulin 22.9+/-10 vs. 21.6+/
      10, and 26.5+/-12 vs. 28.8+/-11, respectively. CONCLUSION: The increase in the
      inner diameter of the hollow fibres did not result in improved convective volume
      and removal capacity.

PMID- 29325672
TI  - Hyperkalemia of non-renal origin in a hemodialysis patient.

PMID- 29325673
TI  - Denosumab anf cronic kidney disease: Severe life-threatening hypocalcemia.

PMID- 29325674
TI  - Unclassifiable idiopathic interstitial pneumonias: A never-ending story?

PMID- 29325675
TI  - Mycophenolate mofetil as a therapeutic agent for interstitial lung diseases in
      systemic sclerosis.
AB  - Systemic sclerosis (SSc) is an intractable disease that causes fibrosis in all
      organs. Approximately 40% of patients with SSc have some degree of interstitial
      lung disease (ILD). One third of patients with SSc and ILD, approximately 15% of
      all patients, have pulmonary lesions, which slowly progress to respiratory
      failure resistant to corticosteroid and other treatments. A randomized controlled
      trial conducted in the United States indicated that one year of treatment with
      oral cyclophosphamide in patients with SSc-ILD had a significant but modest
      beneficial effect on lung function, dyspnea, thickening of the skin, and health
      related quality of life. However, all the effects, except for a sustained impact
      on dyspnea, disappeared approximately one year after stopping oral administration
      of cyclophosphamide. A randomized controlled trial using cyclophosphamide and
      mycophenolate mofetil (MMF) was then held in the United States for 142 patients
      with SSc-ILD. Treatment of SSc-ILD with MMF for two years or cyclophosphamide for
      one year both resulted in significant improvements in lung function over the 2
      year course of the study. Leukopenia and thrombocytopenia occurred less often in
      patients administered MMF than in those administered cyclophosphamide. MMF is
      currently not approved for the treatment of SSc-ILD in Japan. Both MMF and
      cyclophosphamide were effective against ILD associated with SSc and, in
      particular, MMF was useful in terms of tolerability. When MMF is approved, it
      should be positioned as one of the first treatment options for SSc-ILD, which
      will further enhance the treatment of this disease in Japan.

PMID- 29325676
TI  - Respiratory function in healthy ever-smokers is impaired by smoking habits in a
      dose-dependent manner.
AB  - BACKGROUND: There is limited information about the respiratory function of ever
      smokers without lung disorders. We sought to assess the effects of smoking habits
      on respiratory function in subjects without lung disorders. METHODS: Subjects
      were recruited from among patients without any evidence of respiratory disorders
      who visited rural primary care clinics. Each participant was asked to answer a
      questionnaire that included questions smoking history. Their forced vital
      capacity (FVC) and forced expiratory volume in one second (FEV1) were measured.
      RESULTS: We analyzed 802 subjects (364 men and 438 women). The means of the
      lambda-mu-sigma method derived z-score of FEV1 (zFEV1) both in current-smokers
      and ex-smokers were lower than that in never-smokers. The mean zFEV1 in the ever
      smokers with more than 30 pack-years of smoking history were lower than that in
      the ever-smokers with less smoking history. Univariate analysis showed that there
      were significant negative correlations between pack-years and zFEV1 both in the
      ex-smokers and current-smokers. There was no significant correlation between the
      duration of smoking cessation and zFEV1 in the ex-smokers. CONCLUSIONS: Our data
      suggests that respiratory function in healthy ever-smokers is decreased based on
      smoking habits in a dose-dependent manner. Even after a long period of smoking
      cessation, the decreased respiratory function seems to be maintained in ex
      smokers.

PMID- 29325677
TI  - Chronic obstructive pulmonary disease among lung cancer-free smokers: The
      importance of healthy controls.
AB  - BACKGROUND: The prevalence of chronic obstructive pulmonary disease (COPD) in
      smokers enrolled as "healthy" controls in studies is 10-50%. The COPD status of
      ideal smoker populations for lung cancer case-control studies should be checked
      via spirometry; however, this is often not feasible, because no medical
      indications exist for asymptomatic smokers to undergo spirometry prior to study
      enrollment. Therefore, there is an unmet need for robust, cost effective assays
      for identifying undiagnosed lung disease among asymptomatic smokers. Such assays
      would help excluding unhealthy smokers from lung cancer case-control studies.
      METHODS: We used the cytokinesis-blocked micronucleus (CBMN) assay (a measure of
      genetic instability) to identify undiagnosed lung disease among asymptomatic
      smokers. We used a convenience population from an on-going lung cancer case
      control study including smokers with lung cancer (n = 454), smoker controls (n =
      797), and a self-reported COPD (n = 200) contingent within the smoker controls.
      RESULTS: Significant differences for all CBMN endpoints were observed when
      comparing lung cancer to All controls (which included COPD) and Healthy controls
      (with no COPD). The risk ratio (RR) was increased in the COPD group vs. Healthy
      controls for nuclear buds (RR 1.28, 95% confidence interval 1.01-1.62), and
      marginally increased for micronuclei (RR 1.06, 0.98-1.89) and nucleoplasmic
      bridges (RR 1.07, 0.97-1.15). CONCLUSION: These findings highlight the importance
      of using truly healthy controls in studies geared toward assessment of lung
      cancer risk. Using genetic instability biomarkers would facilitate the
      identification of smokers susceptible to tobacco smoke carcinogens and therefore
      predisposed to either disease.

PMID- 29325678
TI  - Is idiopathic PPFE an established subset of idiopathic interstitial pneumonias?

PMID- 29325679
TI  - Prevalence of diabetes mellitus in individuals with airflow obstruction in a
      Japanese general population: The Yamagata-Takahata Study.
AB  - BACKGROUND: Diabetes has been reported as a comorbidity of chronic obstructive
      pulmonary disease (COPD) in Western countries, but it has not been demonstrated
      in epidemiological reports in Japan. The purpose of this study was to clarify
      whether the relationship between airflow obstruction and diabetes can be
      confirmed in a Japanese general population. METHODS: From 2004 to 2006, blood
      sampling and pulmonary function tests were performed on 3045 people over the age
      of 40 years in annual health check-ups held in Takahata, Yamagata Prefecture,
      Japan. Pulmonary function was re-evaluated in 2009 and 2011. RESULTS: The
      prevalence of diabetes did not differ between subjects with and without airflow
      obstruction. Furthermore, although body mass index decreased, no increase in the
      prevalence of diabetes was observed with the progression of airflow obstruction.
      The annual changes in forced expiration volume in 1s (FEV1) did not differ
      depending on the presence or absence of diabetes in the study population.
      CONCLUSION: There was no difference in the prevalence of diabetes between
      subjects with airflow obstruction and those without. As patients with COPD in
      Japan are thinner than in the West, diabetes may not be a common comorbidity in
      Japanese patients with COPD.

PMID- 29325680
TI  - Clinico-radio-pathological characteristics of unclassifiable idiopathic
      interstitial pneumonias.
AB  - BACKGROUND: The purpose of this study was to clarify the clinico-radio
      pathological characteristics and prognostic factors of unclassifiable-idiopathic
      interstitial pneumonias (U-IIPs) diagnosed by surgical lung biopsy. METHODS:
      Among 86 patients with interstitial pneumonia who underwent surgical lung biopsy
      from January 2005 to September 2013, 33 (38.4%; 16 male patients; mean age, 64.4
      +/- 8.8 years) were diagnosed with U-IIPs. They were subsequently categorized
      into rapidly progressive (n = 7), slowly progressive (n = 7), and stable (n = 19)
      groups based on the decrease of the percent predicted forced vital capacity or
      percent predicted diffusing capacity of the lung carbon monoxide and the
      occurrence of acute exacerbation. The clinico-radio-pathological features and
      survival rates of the patients who were followed up for at least 3 years were
      examined. These cases were reevaluated retrospectively by multidisciplinary
      discussion. RESULTS: The rapidly progressive group had a significantly poorer
      prognosis than that of the other groups (p < 0.0001). Although there were no
      significant pattern differences on the chest high-resolution computed tomography,
      the fibrosis scores were significantly higher in the rapidly progressive group (p
      = 0.002). Furthermore, the percentage of fibroblastic foci assessed by the
      pathological analysis was also significantly higher in the rapidly progressive
      group (p = 0.006). Nine (27.3%) patients developed connective tissue diseases
      during follow-up. CONCLUSIONS: The radiologic patterns were not significantly
      different among the three clinical U-IIPs subgroups. Nevertheless, our findings
      suggested that the fibrosis scores and the percentage of fibroblastic foci could
      provide a prognostic assessment in U-IIPs.

PMID- 29325681
TI  - Is hypothyroidism in idiopathic pleuroparenchymal fibroelastosis a novel lung
      thyroid syndrome?
AB  - BACKGROUND: Idiopathic pleuroparenchymal fibroelastosis (IPPFE) is a rare type of
      interstitial pneumonia characterized by fibroelastosis. Patients with IPPFE as
      well as idiopathic interstitial pneumonia often have autoimmune diseases, which
      sometimes coincide with hypothyroidism (HypoT). However, there have been no
      reports on the association between IPPFE and HypoT. The purpose of this study was
      to evaluate the correlation between IPPFE and HypoT. We also examined the
      pathological features of the thyroid glands from autopsied cases. METHODS:
      Thirteen patients diagnosed with IPPFE from among 255 consecutive cases of
      idiopathic interstitial pneumonia were included in this study; pertinent data
      were obtained from our hospital's clinical library. We examined the prevalence of
      HypoT and compared the clinical, radiological, and pathological features between
      the patients with and those without HypoT. Histological analyses of the lungs and
      thyroid glands were performed in 4 and 3 cases, respectively. RESULTS: HypoT was
      identified in 7 of 13 patients (53.8%). Sex, body mass index, survival time, and
      laboratory test results were not significantly different between patients with
      and those without HypoT. Radiological and pathological lung findings were similar
      between both groups of patients. Thyroid gland histology demonstrated
      perifollicular or interlobular fibrosis without inflammation in all three cases,
      including a euthyroid case. CONCLUSIONS: Although we only analyzed a small number
      of IPPFE cases, HypoT was prevalent among all of them. Characteristic fibrosis in
      the thyroid gland was observed even in a euthyroid case. Therefore, patients with
      IPPFE may potentially have thyroid gland dysfunction through a common
      pathogenesis in both organs.

PMID- 29325682
TI  - Computer-based quantitative computed tomography image analysis in idiopathic
      pulmonary fibrosis: A mini review.
AB  - Idiopathic pulmonary fibrosis (IPF) is the most common type of progressive
      idiopathic interstitial pneumonia in adults. Many computer-based image analysis
      methods of chest computed tomography (CT) used in patients with IPF include the
      mean CT value of the whole lungs, density histogram analysis, density mask
      technique, and texture classification methods. Most of these methods offer good
      assessment of pulmonary functions, disease progression, and mortality. Each
      method has merits that can be used in clinical practice. One of the texture
      classification methods is reported to be superior to visual CT scoring by
      radiologist for correlation with pulmonary function and prediction of mortality.
      In this mini review, we summarize the current literature on computer-based CT
      image analysis of IPF and discuss its limitations and several future directions.

PMID- 29325683
TI  - Physical activity in daily life in patients with idiopathic pulmonary fibrosis.
AB  - BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is characterized by progressive
      impairment of lung function and degradation of daily activity; however, this
      degradation has not been adequately elucidated. The objective of this study was
      to measure the physical activity of patients with IPF to determine its
      relationships with physiological parameters and survival rate. METHODS: In total,
      31 patients with IPF and 20 age-matched healthy participants were enrolled in
      this study. Physical activity was assessed using a physical activity monitor. The
      relationships among physical activity, physiological data, questionnaire-based
      patient-centered data, and survival were examined. RESULTS: Physical activity,
      expressed as daily activity energy expenditure (AEE), was significantly lower,
      and the percentage of sedentary time was significantly longer in patients with
      IPF than in healthy participants. Moreover, AEE was moderately correlated with
      body-mass index, forced vital capacity, diffusing capacity of carbon monoxide,
      and partial arterial pressure of oxygen. Relatively strong correlation was also
      observed between AEE and the 6-min walk distance, but not with daily dyspnea,
      depression, and health-related quality of life scores. Prognostic analysis
      indicated that daily AEE was a significant predictor of survival. CONCLUSIONS:
      Patients with IPF were significantly inactive compared with age-matched healthy
      participants. In patients with more impaired physiological functions, the lower
      the physical activity was, the more was the sedentary time increased.
      Furthermore, lower daily physical activity resulted in significantly worse
      survival.

PMID- 29325684
TI  - Respiratory comorbidities and risk of mortality in hospitalized patients with
      idiopathic pulmonary fibrosis.
AB  - BACKGROUND: Respiratory comorbidities are frequently associated with idiopathic
      pulmonary fibrosis (IPF). However, little is known about their prognostic impact
      in hospitalized patients with IPF. We examined the impact of respiratory
      comorbidities on the mortality rates of hospitalized patients with IPF using a
      Japanese nationwide database. METHODS: We identified 5665 hospitalized patients
      diagnosed with IPF between April 2010 and March 2013. The primary outcome was
      defined as the in-hospital mortality at 30 days after admission. The impact of
      respiratory comorbidities was assessed using a Cox proportional hazards model
      that incorporated clinically relevant factors. RESULTS: In hospitalized patients
      with IPF, the prevalence of bacterial pneumonia, pulmonary hypertension, and lung
      cancer were 9.5%, 4.6%, and 3.7%, respectively. Among patients with bacterial
      pneumonia, the four most common pathogens were Streptococcus pneumoniae (31.6%),
      methicillin-resistant Streptococcus aureus (18.4%), Klebsiella pneumoniae (9.2%),
      and Pseudomonas aeruginosa (9.2%). Lung cancer was more commonly found in the
      lower lobes (60.1%) than in other lobes. The survival at 30 days from admission
      was 78.4% in all patients and significantly lower in IPF patients with bacterial
      pneumonia (adjusted hazard ratio [HR], 1.30; 95% confidence interval [CI], 1.04
      1.63; p < 0.023) and patients with lung cancer (adjusted HR, 1.99; 95% CI, 1.47
      2.69; p < 0.001) than in others. Pulmonary hypertension was not associated with
      mortality. IPF patients with one or more of these three respiratory comorbidities
      had a poorer survival than others (p < 0.05). CONCLUSIONS: Respiratory
      comorbidities, especially bacterial pneumonia and lung cancer, influence
      mortality in hospitalized patients with IPF.

PMID- 29325685
TI  - Reduced incidence of lung cancer in patients with idiopathic pulmonary fibrosis
      treated with pirfenidone.
AB  - BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a disease with a worse
      prognosis than some types of cancer. In patients with IPF, lung cancer is
      critical because of the associated high mortality rate from its progression and
      fatal complications from anticancer treatments. Therefore, preventing lung cancer
      in patients with IPF is primordial. Pirfenidone is an anti-fibrotic agent that
      reduces the decline in forced vital capacity. This study aimed to assess the
      effect of pirfenidone in the development of lung cancer in patients with IPF.
      METHODS: Data from 261 patients with IPF with and without pirfenidone were
      retrospectively reviewed, and the incidence of lung cancer was analyzed. RESULTS:
      In the pirfenidone group, the incidence of lung cancer was significantly lower
      than in the non-pirfenidone group (2.4% vs. 22.0%, P < 0.0001). Multivariate Cox
      proportional hazards regression analysis demonstrated that pirfenidone decreased
      the risk of lung cancer (hazard ratio, 0.11; 95% confidence interval, 0.03 to
      0.46; P = 0.003), whereas coexisting emphysema increased the incidence of lung
      cancer (hazard ratio, 3.22; 95% confidence interval, 1.35 to 7.70; P = 0.009).
      CONCLUSIONS: Pirfenidone might correlate with a decreased risk of lung cancer in
      patients with IPF. However, no definite conclusion can be drawn from this
      retrospective study, and a multicenter, prospective cohort study is still
      warranted to confirm the effect of pirfenidone on lung cancer in patients with
      IPF.

PMID- 29325686
TI  - Phase II study of tailored S-1 monotherapy with a 1-week interval after a 2-week
      dosing period in elderly patients with advanced non-small cell lung cancer.
AB  - BACKGROUND: S-1 is an oral fluoropyrimidine that is active in the treatment of
      non-small cell lung cancer (NSCLC); however, an optimal treatment schedule and
      appropriate dose adjustments of S-1 in elderly patients have not yet been
      established. METHODS: We conducted a phase II trial to evaluate the efficacy and
      safety of a 2-week S-1 monotherapy treatment followed by a 1-week interval as a
      first-line treatment of elderly NSCLC patients, by adjusting the dose based on
      the individual creatinine clearance (Ccr) and body surface area (BSA). The
      primary endpoint was the disease control rate. RESULTS: Forty patients were
      enrolled. The disease control and response rates were 89.5% (95% confidence
      interval [CI] = 79.8-99.2) and 7.9% (95% CI = 0.0-16.4), respectively. The median
      progression-free survival and overall survival times were 4.4 months (95% CI =
      4.2-8.5) and 17.0 months (95% CI = 11.2-18.7), respectively. Neutropenia,
      anorexia, hyponatremia, hypokalemia, and pneumonia of grade >= 3 occurred in
      5.0%, 7.5%, 5.0%, 2.5%, and 2.5% of patients, respectively. Among the patient
      reported outcomes, most of the individual factors in the patients' quality of
      life, including upper intestine-related symptoms improved with the treatment,
      except for dyspnea, which slightly albeit continuously worsened throughout the
      study. CONCLUSIONS: In elderly patients with previously untreated advanced NSCLC,
      a 2-week S-1 monotherapy treatment, tailored to both the Ccr and BSA, with a 1
      week interval was well tolerated and demonstrated promising efficacy. This study
      was registered at the University Hospital Medical Information Network (UMIN)
      Center (ID: UMIN000002035), Japan.

PMID- 29325688
TI  - An impact factor for the 60 candles of the Annals.

PMID- 29325689
TI  - Osteoporosis: Heading Towards the Perfect Storm.

PMID- 29325687
TI  - Clinical significance and epidemiologic analyses of Mycobacterium avium and
      Mycobacterium intracellulare lung disease from post-marketing surveillance.
AB  - BACKGROUND: In Japan, nontuberculous mycobacterial lung disease is mostly
      attributable to Mycobacterium avium complex (MAC), i.e., M. avium or M.
      intracellulare. However, clinical features of the disease caused by these two
      pathogens have not been studied sufficiently yet. METHODS: A post-marketing
      survey of clarithromycin was performed at 130 facilities across Japan. The data
      on patients with M. avium infection and patients with M. intracellulare infection
      were selected from this survey for comparison of background variables and
      clinical features of the two pathogens. RESULTS: Among the patients analyzed (n =
      368), 67.4% had M. avium infection and 32.6% had M. intracellulare infection.
      Stratified analysis revealed no significant differences between the ratio of the
      two pathogens based on gender, disease type, complication, past medical history,
      or smoking history. However, the percentage of patients with M. intracellulare
      infection was significantly higher among those with underlying lung disease than
      among those without lung disease (p = 0.0217). The percentage of patients with M.
      intracellulare infection rose significantly with age (p = 0.0296). This age
      related change was more significant in women (p = 0.0018). When district-wise
      analysis was performed for Japan, the percentage of M. intracellulare infection
      was higher in the Chugoku/Shikoku and Kyushu districts whereas the percentage of
      M. avium infection was higher in the other districts. CONCLUSIONS: This survey
      revealed some differences in the clinical and epidemiologic features of M. avium
      and M. intracellulare infection. The significant predominance of M. avium
      infection among relatively young women is suggestive of an increase in the M.
      avium/M. intracellulare infection ratio among women in the future.

PMID- 29325691
TI  - Predictors of recurrent sprains after an index lateral ankle sprain: a
      longitudinal study.
AB  - OBJECTIVE: To explore and identify the predictors of ankle sprain after an index
      (first) lateral ankle sprain. DESIGN: Prospective cohort study, Level of evidence
      II. SETTING: Musculoskeletal research laboratory at the University of Sydney.
      PARTICIPANTS: A sample of convenience (70 controls, 30 with an index sprain) was
      recruited. METHODS: Potential predictors of ankle sprain were measured including:
      demographic measures, perceived ankle instability, ankle joint ligamentous
      laxity, passive range of ankle motion, balance, proprioception, motor planning
      and control, and inversion/eversion peak power. Participants were followed up
      monthly and the number of ankle sprains was recorded over 12 months. RESULTS:
      Ninety-six participants completed the study; 10 participants sustained an ankle
      sprain. A combination of 10 predictors including: a recent index sprain, younger
      age, greater height and weight, perceived instability, increased laxity, impaired
      balance, and greater inversion/eversion peak power explained 27 to 56% of the
      variance in occurrence of ankle sprain (chi211,95=30.67, p=0.001). The regression
      model correctly classified 90% of cases. The strongest independent predictors
      were history of an index sprain (odds ratio (OR)=8.23, 95% confidence interval
      (CI)=1.66 to 40.72) and younger age (OR=8.41, 95%CI=1.48 to 47.96). CONCLUSION: A
      recent index ankle sprain and younger age were the only independent predictors of
      ankle sprain. The combination of greater height or weight, feeling of
      instability, peak power and impaired balance predicted the occurrence of ankle
      sprain in almost 90% of participants. These findings could form the basis for
      intervention targeted at reducing recurrence of sprain after an index sprain.

PMID- 29325690
TI  - Dose-volume effects in pathologic lymph nodes in locally advanced cervical
      cancer.
AB  - OBJECTIVE: In cervical cancer patients, dose-volume relationships have been
      demonstrated for tumor and organs-at-risk, but not for pathologic nodes. The
      nodal control probability (NCP) according to dose/volume parameters was
      investigated. MATERIAL AND METHODS: Patients with node-positive cervical cancer
      treated curatively with external beam radiotherapy (EBRT) and image-guided
      brachytherapy (IGABT) were identified. Nodal doses during EBRT, IGABT and boost
      were converted to 2-Gy equivalent (alpha/beta = 10 Gy) and summed. Pathologic
      nodes were followed individually from diagnosis to relapse. Statistical analyses
      comprised log-rank tests (univariate analyses), Cox proportional model (factors
      with p <= 0.1 in univariate) and Probit analyses. RESULTS: A total of 108
      patients with 254 unresected pathological nodes were identified. The mean nodal
      volume at diagnosis was 3.4 +/- 5.8 cm3. The mean total nodal EQD2 doses were
      55.3 +/- 5.6 Gy. Concurrent chemotherapy was given in 96%. With a median follow
      up of 33.5 months, 20 patients (18.5%) experienced relapse in nodes considered
      pathologic at diagnosis. Overall nodal recurrence rate was 9.1% (23/254). On
      univariate analyses, nodal volume (threshold: 3 cm3, p < .0001) and lymph node
      dose (>=57.5 Gyalpha/beta10, p = .039) were significant for nodal control. The
      use of simultaneous boost was borderline for significance (p = .07). On
      multivariate analysis, volume (HR = 8.2, 4.0-16.6, p < .0001) and dose (HR = 2,
      1.05-3.9, p = .034) remained independent factors. Probit analysis combining dose
      and volume showed significant relationships with NCP, with increasing gap between
      the curves with higher nodal volumes. CONCLUSION: A nodal dose-volume effect on
      NCP is demonstrated for the first time, with increasing NCP benefit of additional
      doses to higher-volume nodes.

PMID- 29325692
TI  - Ontogenetic and temperature-dependent changes in tolerance to hypoxia and
      hydrogen sulfide during the early life stages of the Manila clam Ruditapes
      philippinarum.
AB  - Wind-induced upwelling of hypoxic waters containing hydrogen sulfide (H2S)
      sometimes causes mass mortalities of aquatic organisms inhabiting coastal areas,
      including the hypoxia-tolerant Manila clam Ruditapes philippinarum. We examined
      the tolerance of Manila clam to H2S under controlled laboratory conditions.
      Larvae and juveniles obtained by artificial fertilization or from a wild
      population were exposed to normoxic or to hypoxic water with or without un
      ionized H2S (concentrations, 0.2-52.2 mg/L). Twenty-four-hour exposure
      experiments revealed ontogenetic changes in the clam's tolerance to H2S exposure:
      tolerance was enhanced from the larval stages to juveniles just after settlement
      but was attenuated as juveniles grew. Tolerance of larvae and juveniles to H2S
      exposure weakened as the water temperature rose from 20 to 28  degrees C.
      Prolonged 48-h exposure to H2S attenuated the tolerance of juveniles to H2S.
      Temporary suspension of H2S exposure by 24-h reoxygenation improved the ability
      of juveniles to withstand repeated H2S exposure.

PMID- 29325693
TI  - Updates in the Eighth Edition of the Tumor-Node-Metastasis Staging Classification
      for Urologic Cancers.
AB  - : The Tumor-Node-Metastasis (TNM) classification on cancer staging, jointly
      developed by the American Joint Commission on Cancer (AJCC) and the Union for
      International Cancer Control (UICC), has been updated to its 8th edition with two
      contemporaneous versions published by the AJCC and UICC. While the goal of the
      AJCC and UICC is to have identical TNM staging systems, differences exist between
      these two publications including in the staging of urologic cancers. Among
      several new facets in the AJCC staging manual, a select few of greater import
      include an expanded section on imaging, presentation of levels of evidence for
      significant changes, and endorsement of risk assessment models that pass the AJCC
      quality criteria such as in prostate cancer. The updates for urologic cancers in
      the AJCC stage categories can be grouped into: (1) newly defined TNM categories
      and prognostic stage groupings, (2) clarifications and refinements of previously
      defined categories, and (3) more systematic and expanded presentation of
      prognostic factors. Changes are harmonized with the current reporting and
      treatment guidelines. Contributions from genitourinary pathology are evident in
      the AJCC classification from many of the International Society of Urological
      Pathology (ISUP) consensus conferences on prostate, kidney, testicular, and
      penile neoplasms that addressed staging issues and the timely publication of the
      4th edition of the World Health Organization (WHO) classification of urinary and
      male genital organ tumors. New grading approaches for penile (WHO/ISUP grade),
      prostate (Grade group), and kidney (WHO/ISUP nucleolar grade) cancers were
      adopted in the AJCC system. Many of these updates in the AJCC staging manual are
      also included in the 8th UICC TNM edition. In an effort to achieve the optimal
      staging recommendations for urologic cancers, updates in the 8th TNM edition were
      generated through the acquisition of best evidences, tapping interdisciplinary
      resources including consensus recommendations, and enhanced data analysis.
      PATIENT SUMMARY: In this report, we explain the seminal changes in the 8th
      edition of the Tumor-Node-Metastasis staging system for urologic cancers. Major
      stage category definitional changes are in Tumor-Node-Metastasis classifications
      of testicular, penile, and prostate cancer which improve patient stratification
      for prognosis and management.

PMID- 29325694
TI  - Numerical modeling of polymorphic transformation of oleic acid via near-infrared
      spectroscopy and factor analysis.
AB  - Near-infrared (NIR) spectroscopy as a tool for direct and quantitatively
      screening the minute polymorphic transitions of bioactive fatty acids was
      assessed basing on a thermal heating process of oleic acid. Temperature-dependent
      NIR spectral profiles indicate that dynamical variances of COOH group dominate
      its gamma -> alpha phase transition, while the transition from active alpha to
      beta phase mainly relates to the conformational transfer of acyl chain. Through
      operating multivariate curve resolution-alternating least squares with factor
      analysis, instantaneous contribution of each active polymorph during the
      transition process was illustrated for displaying the progressive evolutions of
      functional groups. Calculated contributions reveal that the alpha phase of oleic
      acid initially is present at around -18  degrees C, but sharply grows up around 
      2.2  degrees C from the transformation of gamma phase and finally disappears at
      the melting point. On the other hand, the beta phase of oleic acid is sole self
      generation after melt even it embryonically appears at -2.2  degrees C. Such
      mathematical approach based on NIR spectroscopy and factor analysis calculation
      provides a volatile strategy in quantitatively exploring the transition processes
      of bioactive fatty acids; meanwhile, it maintains promising possibility for
      instantaneous quantifying each active polymorph of lipid materials.

PMID- 29325695
TI  - Investigation of the uterine structural changes in the experimental model with
      polycystic ovary syndrome and effects of vitamin D treatment: An ultrastructural
      and immunohistochemical study.
AB  - In this study, we aimed to investigate the structural changes seen in the
      endometrium in experimental PCOS rat model and the effects of vitamin D treatment
      on these changes at immunohistochemical and electron microscopic levels. 24
      prepubertal female rats were divided into three groups. Two groups were injected
      with dehydroepiandrosterone and one of them was treated with 1,25(OH)2 D3 at the
      same time. The control group was injected with sesame oil. At the end of the 28th
      day, the blood samples were collected. Uterus tissues were prepared for light and
      electron microscopic examinations. Epithelial, stromal and endometrial thickness
      measurements were investigated. Immunohistochemical staining was applied against
      caspase-3 and Ki-67. Serum AMH and estradiol levels were higher in PCOS group
      compared to the control group. Serum progesterone levels were similar in all
      groups. Endometrial, epithelial and stromal thickness measurements were increased
      in PCOS group compared to the control group, and decreased in the vitamin D
      treatment group compared to the PCOS group. Light and electron microscopic
      results of PCOS group showed an increase in apoptosis and proliferation. In the
      PCOS group, immunohistochemical staining of caspase-3 and Ki-67 were found to be
      higher than in the control group, but stainings were decreased with vitamin D
      treatment compared to PCOS group. Structural changes observed in endometrium may
      be related to implantation problems seen in patients with PCOS. Our studies
      suggest that vitamin D therapy may be beneficial in these patients.

PMID- 29325697
TI  - Early Stable Sinus Rhythm Associated With Greater Success 5 Years After Surgical
      Ablation.
AB  - BACKGROUND: An important challenge in surgical ablation for atrial fibrillation
      (AF) is the scarcity of publications on credible predictors of long-term success
      in procedures performed with ablation tools that produce consistently reliable
      transmural lesions. We examined factors associated with 1-year success and no
      atrial arrhythmia (AA) recurrence during 1 to 5 years after surgical ablation for
      AF. METHODS: The study prospectively monitored 743 surgical ablation patients
      with complete rhythm follow-up at 12 months after the operation. No detected AA
      was defined as no known recurrence of AA, no cardioversions, and no catheter
      ablations at all available follow-up assessments. RESULTS: Patients were a mean
      age of 64.7 years, and 32% were women. Patients with no detected AA during the
      first year after surgical ablation were more likely to maintain sinus rhythm
      without recurrence during 1 to 5 years (74% vs 28%, p < 0.001) and to be in sinus
      rhythm off medication at 5 years (80% vs 53%, p < 0.001). Mixed-model logistic
      regression revealed that lower risk for AA recurrence during 1 to 5 years was
      associated with no detected AA during the first 12 months (odds ratio [OR], 0.11;
      p < 0.001) and surgeon experience with 50 or more cases (OR, 0.63; p = 0.043),
      whereas older age (OR, 1.03; p < 0.001) and longer preoperative AF duration (OR,
      1.04; p = 0.043) were associated with greater risk for AA recurrence.
      CONCLUSIONS: Most patients with no detected AA throughout the first 12 months
      after surgical ablation continued to be recurrence free for 5 years. Younger age,
      shorter preoperative AF duration, and greater surgeon experience may be
      associated with more persistent surgical correction of AF.

PMID- 29325696
TI  - Urinary mRNA analysis of biomarkers to epithelial mesenchymal transition of renal
      allograft.
AB  - Renal allograft loss is most often a chronic process, irrespective of the
      mechanism at stake. In this prospective study, we studied the expression of
      epithelial to mesenchymal transition (EMT) markers vimentin and beta-catenin by
      immunohistochemistry in the surveillance biopsy and measured the mRNA encoding
      vimentin (VIM), CD45, GAPDH and uroplakin 1a (UPK) by quantitative PCR in urinary
      cells in 75 renal transplant patients. The aim is to establish a simple screening
      test for chronic renal allograft dysfunction. We found that the value of the mRNA
      of vimentin and CD45 relative to the uroplakin 1a (UPK) mRNA is correlated with
      the score in vimentin immunostaining in routine biopsies. These biomarkers could
      be used as a noninvasive tool to monitor the renal graft fibrogenesis. This test
      could be used for early detection of fibrotic diseases of the kidney transplant.

PMID- 29325698
TI  - What causes childhood stunting among children of San Vicente, Guatemala:
      Employing complimentary, system-analysis approaches.
AB  - Guatemala has the sixth worst stunting rate with 48% of children under five years
      of age classified as stunted according to World Health Organization standards.
      This study utilizes two different yet complimentary system-analysis approaches to
      analyze correlations among environmental and demographic variables, environmental
      enteric dysfunction (EED), and child height-for-age (stunting metric) in
      Guatemala. Two descriptive models constructed around applicable environmental and
      demographic factors on child height-for-age and EED were analyzed using Network
      Analysis (NA) and Structural Equation Modeling (SEM). Data from two populations
      of children between the age of three months and five years were used. The first
      population (n = 2103) was drawn from the Food for Peace Baseline Survey conducted
      by the US Agency for International Development (USAID) in 2012, and the second
      population (n = 372) was drawn from an independent survey conducted by the San
      Vicente Health Center in 2016. The results from the NA of the height-for-age
      model confirmed pathogen exposure, nutrition, and prenatal health as important,
      and the results from the NA of the EED model confirmed water source, water
      treatment, and type of sanitation as important. The results from the SEM of the
      height-for-age model confirmed a statistically significant correlation among
      child height-for-age and child-mother interaction (-0.092, p = 0.076) while the
      SEM of the EED model confirmed the statistically significant correlation among
      EED and type of water treatment (-0.115, p = 0.013). Our approach supports
      important efforts to understand the complex set of factors associated with child
      stunting among communities sharing similarities with San Vicente.

PMID- 29325700
TI  - 2017 reviewers.

PMID- 29325699
TI  - Co-delivery of tumor antigen and dual toll-like receptor ligands into dendritic
      cell by silicon microparticle enables efficient immunotherapy against melanoma.
AB  - Despite the importance and promise of cancer vaccines for broader prevention and
      treatment of cancer, limited clinical responses are observed, suggesting that key
      rational designs are required for inducing potent immune responses against
      cancer. Here we report a mesoporous silicon vector (MSV) as a multi-functional
      microparticle for formulating an efficient cancer vaccine composed of B16
      melanoma derived-tyrosinase related protein 2 (TRP2) peptide and dual toll-like
      receptor (TLR) agonists. We demonstrated that MSV microparticles protected the
      peptide from rapid degradation for prolonged antigen presentation to immune
      cells. Moreover, MSV enabled co-delivery of two different TLR agonists [CpG
      oligonucleotide and monophosphoryl lipid A (MPLA)] along with TRP2 peptide into
      the same dendritic cell (DC), thus increasing the efficiency and capacity of DCs
      to induce potent TRP2-specifc CD8+ T cell responses against B16 melanoma.
      Furthermore, this MSV-based DC vaccine could significantly prolong the median
      survival of tumor-bearing mice by orchestrating effective host immune responses
      involving CD8+ T cells, CD4+ T cells and macrophages. Our study provides rational
      and potentially translational approach to develop durable and potent
      immunotherapy for patients with cancer by delivering various combinations of
      tumor antigens, neoantigens and innate immune agonists.

PMID- 29325701
TI  - Developmental cognitive neuroscience using latent change score models: A tutorial
      and applications.
AB  - Assessing and analysing individual differences in change over time is of central
      scientific importance to developmental neuroscience. However, the literature is
      based largely on cross-sectional comparisons, which reflect a variety of
      influences and cannot directly represent change. We advocate using latent change
      score (LCS) models in longitudinal samples as a statistical framework to tease
      apart the complex processes underlying lifespan development in brain and
      behaviour using longitudinal data. LCS models provide a flexible framework that
      naturally accommodates key developmental questions as model parameters and can
      even be used, with some limitations, in cases with only two measurement
      occasions. We illustrate the use of LCS models with two empirical examples. In a
      lifespan cognitive training study (COGITO, N = 204 (N = 32 imaging) on two waves)
      we observe correlated change in brain and behaviour in the context of a high
      intensity training intervention. In an adolescent development cohort (NSPN, N =
      176, two waves) we find greater variability in cortical thinning in males than in
      females. To facilitate the adoption of LCS by the developmental community, we
      provide analysis code that can be adapted by other researchers and basic primers
      in two freely available SEM software packages (lavaan and Omeganyx).

PMID- 29325703
TI  - The prevalence and morphometric analysis of ossified superior transverse scapular
      ligaments in patients with rotator cuff tears.
AB  - BACKGROUND: The prevalence of ossified superior transverse scapular ligaments
      (OSTSLs) in rotator cuff tears (RCTs) has not yet been determined. The purposes
      of this study were to evaluate the prevalence of OSTSLs in RCTs and to
      investigate the correlation between OSTSL morphology and supraspinatus muscle
      atrophy. METHODS: We analyzed a total of 213 patients with RCTs for whom 3
      dimensional (3D) computed tomography (CT) and magnetic resonance imaging were
      performed prior to arthroscopic procedures. The mean age of the patients was
      59.73 +/- 8.43 years, and 103 patients were men. OSTSLs were identified based on
      3D CT findings. The correlations between OSTSLs and age, sex, and RCT size were
      analyzed. The horizontal and vertical diameters, area, and circumference of the
      suprascapular foramen were measured. By use of the occupation ratio calculated
      from magnetic resonance imaging results, supraspinatus muscle atrophy was
      evaluated. RESULTS: Of 213 patients with RCTs, 22 (10.3%) had OSTSLs. OSTSLs were
      found at a rate of 15.5% (16 of 103) in men, higher than that in women (P =
      .016). The rate of OSTSLs increased with age (P = .003). RCT size was not
      correlated with the prevalence of OSTSLs. As the horizontal diameter and
      circumference of the suprascapular foramen increased, muscle atrophy progressed
      (P = .001 and P = .046, respectively). CONCLUSION: One of ten patients with RCTs
      had OSTSLs; the rate of OSTSLs was higher among men and increased with age. For
      patients with RCTs preparing to undergo arthroscopic superior transverse ligament
      resection, preoperatively identifying OSTSLs through 3D CT would be useful for
      the resection.

PMID- 29325705
TI  - Intra-test and test-retest reliability of exercise oximetry in arterial
      claudication.
AB  - BACKGROUND: Transcutaneous oxygen pressure (tcpO2) reliability is blunted by an
      unpredictable transcutaneous gradient through the skin. We hypothesized that the
      "Decrease from Rest of Oxygen pressure (DROP: subtraction of limb-changes from
      chest-changes from the respective starting values) would show a good to excellent
      reliability during Exercise -tcpO2 investigations. METHODS: In three different
      experiments we tested: The intra-test variability at the peripheral level
      (Experiment A: 32 patients, 16 at each location), at the chest level (Experiment
      B: 45 patients) and the test-retest reproducibility within 3 months (Experiment
      C: 67 patients). We calculated the intra-class coefficient of correlation (ICC)
      with 95% confidence interval [Lower/upper limit]. ICC between 0.60 and 0.749
      indicate a good agreement. ICC above 0.750 indicates an excellent agreement.
      RESULTS: ICC values for DROP-min were 0.848 [0.723/0.935] at the buttock and
      0.920 [0.846/0.967] at the calf levels, in experiment A; ICC were 0.873
      [0.799/0.923] at the buttock and 0.898 [0.790/0.953] at the calf levels, in
      experiment B; 0.806 [0.716/0.871] at then buttock level (n = 67) and 0.807
      [0.722/0.868] at the calf in experiment C. CONCLUSIONS: Intra-test and test
      retest reliability is excellent using the DROP calculation for exercise-tcpO2
      investigations.

PMID- 29325704
TI  - Psychometrics of the Patient-Reported Outcomes Measurement Information System
      Physical Function instrument administered by computerized adaptive testing and
      the Disabilities of Arm, Shoulder and Hand in the orthopedic elbow patient
      population.
AB  - BACKGROUND: This study evaluated the psychometric properties of the Patient
      Reported Outcomes Measurement Information System (PROMIS) Physical Function (PF)
      instrument administered through computerized adaptive testing (CAT) compared with
      the traditional full-length Disabilities of the Arm, Shoulder and Hand (DASH).
      METHODS: The PROMIS PF CAT and the DASH were administered to 1759 patients
      seeking care for elbow conditions. This study used Rasch partial credit modeling
      to analyze the instruments with item fit, internal reliability, response category
      thresholds, dimensionality, local independence, gender differential item
      functioning, and floor and ceiling effects. RESULTS: The PROMIS PF CAT and DASH
      had satisfactory item fit for all but 1 item on both measures. Internal
      reliabilities were high for both measures. Two items on the DASH and 4 items on
      the PF CAT showed nonordered category thresholds. Unidimensionality was adequate,
      and local independence was supported for both instruments. Gender bias was found
      for 4 items on the PF CAT and 12 items on the DASH. Both measures had adequate
      instrument targeting and satisfactory floor and ceiling effects. CONCLUSION: The
      PROMIS PF CAT and the DASH both showed sufficient unidimensionality, good item
      fit, and good local independence with the exception of high levels of gender item
      bias, particularly for the DASH. Further scale evaluation should address item
      bias and item response categories for these instruments. Overall, the PROMIS PF
      CAT is an effective outcome instrument to measure function in patients with elbow
      disorders that requires significantly fewer questions than the DASH.

PMID- 29325706
TI  - Contrast harmonic EUS for the prediction of pancreatic neuroendocrine tumor
      aggressiveness (with videos).
AB  - BACKGROUND AND AIMS: Contrast harmonic EUS (CH-EUS) has the ability to depict
      tumor microvasculature. Decreased microvascular density has been identified as a
      factor associated with tumor aggressiveness. We aimed to study the accuracy of CH
      EUS for the prediction of pancreatic neuroendocrine tumor (PNET) aggressiveness.
      METHODS: Between June 2009 and March 2015, all consecutive patients with
      histology-proven PNETs and CH-EUS examination were included. Nine
      endosonographers blindly analyzed all videos. CH-EUS tumor aggressiveness was
      defined as a heterogeneous enhancement at the early arterial phase. The final
      diagnosis of tumor aggressiveness was defined as follows: G3 tumors, morphologic
      and/or histologic findings of metastatic disease in G1/G2 tumors. Diagnostic
      values were calculated. Intratumoral microvascular density and fibrosis were
      assessed on pathologic specimens. RESULTS: Eighty-one tumors were included, of
      which 26 were aggressive (32.1%). In CH-EUS 35 tumors (43.2%) had a heterogeneous
      enhancement. The overall accuracy, sensitivity, specificity, positive predictive
      value, and negative predictive value of CH-EUS for the diagnosis of tumor
      aggressiveness were 86%, 96%, 82%, 71%, and 98%, respectively. The interobserver
      agreement among the 9 endosonographers was good (k = .66). The intraobserver
      agreement was excellent for the junior (kappa = .83) and senior (kappa = .82)
      endosonographers. Heterogeneous tumors at CH-EUS corresponded to fewer vascular
      and more fibrotic tumors (P < .01). CONCLUSIONS: CH-EUS is accurate in the
      prediction of PNET aggressiveness and could be a decision-making element in their
      management.

PMID- 29325708
TI  - Promising roles for pharmacists in addressing the U.S. opioid crisis.
AB  - Overdoses of prescription or illicit opioids claimed the lives of 116 Americans
      each day in 2016, and the crisis continues to escalate. As healthcare systems
      evolve to address the crisis, the potential of pharmacists to make a positive
      difference is significant. In addition to utilizing available prescription drug
      monitoring programs to help prevent diversion of opioids, practicing pharmacists
      can be alert for signs of opioid misuse by patients (e.g., multiple prescriptions
      from different physicians) as well as inappropriate prescribing or hazardous drug
      combinations that physicians may not be aware of (e.g., opioid analgesics
      combined with benzodiazepines). They can also supply patients with information on
      risks of opioids, proper storage and disposal of medications, and the harms (and
      illegality) of sharing medications with other people. Increasingly, pharmacies
      are sites of distribution of the opioid antagonist naloxone, which has been shown
      to save lives when made available to opioid users and their families or other
      potential bystanders to an overdose; and pharmacists can provide guidance about
      its use and even legal protections for bystanders to an overdose that customers
      may not be aware of. Pharmacists can also recommend addiction treatment to
      patients and be a resource for information on addiction treatment options in the
      community. As addiction treatment becomes more integrated with general
      healthcare, pharmacies are also increasingly dispensing medications like
      buprenorphine and, in the future, possibly methadone. Pharmacists in private
      research labs and at universities are helping to develop the next generation of
      addiction treatments and safer, non-addictive pain medications; they can also
      play a role in implementation research to enhance the delivery of addiction
      interventions and medications in pharmacy settings. Meanwhile, pharmacists in
      educational settings can promote improved education about the neurobiology and
      management of pain and its links to opioid misuse and addiction.

PMID- 29325707
TI  - Successful creation of pancreatic cancer organoids by means of EUS-guided fine
      needle biopsy sampling for personalized cancer treatment.
AB  - BACKGROUND AND AIMS: Pancreatic cancer organoids are tumor models of
      individualized human pancreatic ductal adenocarcinoma (PDA), created from
      surgical specimens and used for personalized treatment strategies. Unfortunately,
      most patients with PDA are not operative candidates. Creation of human PDA
      organoids at the time of initial tumor diagnosis is therefore critical. Our aim
      was to assess the feasibility of creating human PDA organoids by EUS fine-needle
      biopsy (EUS-FNB) sampling in patients with PDA. METHODS: In this prospective
      clinical trial in patients referred to evaluate a pancreatic mass, EUS-FNA was
      performed for initial onsite diagnosis. Two additional needle passes were
      performed with a 22-gauge FNB needle for organoid creation. Primary outcome was
      successful isolation of organoids within 2 weeks of EUS-FNB sampling (P0, no
      passages), confirmed by organoid morphology and positive genotyping. RESULTS:
      Thirty-seven patients with 38 PDA tumors were enrolled. Successful isolation of
      organoids (P0) was achieved in 33 of 38 tumors (87%). Establishment of PDA
      organoid lines for >=5 passages of growth (P5, five passages) was reached in 25
      of 38 tumors (66%). In the single patient with successful P5 FNB sampling-derived
      and P5 surgically derived organoids, there was identical matching of specimens.
      There were no serious adverse events. Two patients developed bleeding at the EUS
      FNB puncture site requiring hemostasis clips. CONCLUSIONS: Pancreatic cancer
      organoids can be successfully and rapidly created by means of EUS-FNB sampling
      using a 22-gauge needle at the time of initial diagnosis. Successful organoid
      generation is essential for precision medicine in patients with pancreatic cancer
      in whom most are not surgically resectable. (Clinical trial registration number:
      NCT03140592.).

PMID- 29325709
TI  - Acute hyperoxia induces systemic responses with no major changes in peripheral
      tissues in the Senegalese sole (Solea senegalensis Kaup, 1858).
AB  - Senegalese sole Solea senegalensis is currently farmed in recirculation
      aquaculture systems that often involve water re-oxygenation, which in turn may
      cause acute or prolonged hyperoxia exposures. In order to understand the impact
      of acute hyperoxia on the fish immune system and peripheral tissues such as gills
      and gut, Senegalese sole juveniles (30.05 +/- 1.72 g) were exposed to normoxia
      (100% O2sat) as control and two hyperoxic conditions (150 and 200% O2sat) and
      sampled at 4 and 24 h. Fish haematological profile, total and differential blood
      cell counts and plasma immune parameters were analysed. Histomorphology and
      immunofluorescence analyses of gills and intestine were performed, respectively,
      whereas head-kidney samples were used for assessing the expression of immune
      related genes. Results indicate that acute hyperoxia exposure may reduce fish
      erythrocyte and haemoglobin levels. Moreover, decreases in total leucocytes
      numbers, circulating lymphocytes, monocytes, alternative complement pathway
      activity and expression of cyclooxygenase-2 were observed in fish exposed to
      hyperoxia. In contrast, hyperoxia did not induce major effects on gill
      histomorphology nor in the protein content of ion and glucose cotransporters as
      well as a macrophage marker (V-ATPase) in the intestine. Although the activation
      of humoral mechanisms and immune-related genes were not dramatically affected by
      acute hyperoxia, the compromised immune cell status and the reduction of some
      inflammatory indicators are issues to consider under acute hyperoxia conditions.

PMID- 29325710
TI  - Wnt5b regulates apoptosis in Litopenaeus vannamei against white spot syndrome
      virus.
AB  - The Wnt signaling mediated by Wnt proteins that orchestrate and influence a
      myriad of cellular processes, such as cell proliferation, differentiation,
      tumorigenesis, apoptosis, and participation in immune defense during microbe
      infection. Wnt5b is one of the Wnt signaling molecules that initiate the cascade.
      In this study, we cloned and characterized a Wnt5b homolog from Litopenaeus
      vannamei designed as LvWnt5b. The full length of LvWnt5b transcript was 1726 bp
      with an 1107 bp open reading frame that encoded a 368 aa protein, which contained
      24 discontinuous and highly conserved cysteine. Real-time quantitative PCR showed
      that the transcriptional level of LvWnt5b was down-regulated when infected with
      white spot syndrome virus (WSSV). Knock-down of LvWnt5b resulted in inhibition of
      the transcriptional level of WSSV gene ie1, indicating that LvWnt5b mediated
      signaling pathway may play an important role in defense against WSSV infection.
      When LvWnt5b was silenced, caspase3/7 activity in hemocytes was increased
      significantly, and the transcription of viral gene was decreased as well.
      Moreover, overexpression of LvWnt5b in HEK293T cells led to inhibition of
      caspase3/7 activity, which further proved the role of LvWnt5b in restraining
      apoptosis. The study showed that the shrimp may decrease the expression of
      LvWnt5b initiatively to act as an immune defense mechanism against WSSV infection
      via promoting apoptosis. It will be helpful for understanding the function of Wnt
      signaling pathway in virus invasion and host defense.

PMID- 29325711
TI  - Effects of cortisol and lipopolysaccharide on expression of select growth-,
      stress- and immune-related genes in rainbow trout liver.
AB  - Many studies have shown that stress-induced cortisol levels negatively influence
      growth and immunity in finfish. Despite this knowledge, few studies have assessed
      the direct effects of cortisol on liver immune function. Using real-time PCR, the
      expression of three cortisol-responsive genes (GR: glucocorticoid receptor, IGF
      1: insulin-like growth factor-I and SOCS-1: suppressor of cytokine signaling-I),
      genes involved with innate and adaptive immunity (IL-1beta: interleukin-1 beta,
      IgM: immunoglobin-M and Lyz: lysozyme), and liver-specific antimicrobial peptides
      (hepcidin and LEAP-2A: liver-expressed antimicrobial peptide-2A) was studied in
      vitro using rainbow trout liver slices. The abundances of GR, SOCS-1 and IGF-1
      mRNAs were suppressed by cortisol treatment. Abundance of IL-1beta mRNA was
      upregulated by LPS and suppressed by cortisol treatment in a time-dependent
      manner. While abundance of IgM mRNA was suppressed by cortisol treatment and
      stimulated by LPS, there were no effects of cortisol or LPS on abundance of Lyz
      mRNA. Abundance of hepcidin and LEAP-2A mRNA levels were suppressed by cortisol
      treatment and stimulated by LPS. These results demonstrate that cortisol directly
      suppresses abundance of GR, IGF-1, IL-1beta, IgM, hepcidin, LEAP-2A and SOCS-1
      mRNA transcripts in the rainbow trout liver. We report for the first time, a
      suppressive effect of cortisol (within 8 h of treatment) on hepcidin and LEAP-2A
      mRNAs in rainbow trout liver, which suggests that acute stress may negatively
      affect liver immune function in rainbow trout.

PMID- 29325712
TI  - A novel GATA-like zinc finger transcription factor involving in hematopoiesis of
      Eriocheir sinensis.
AB  - GATA transcription factor is a family of DNA-binding proteins that can recognize
      and bind to sequence of (A/T) GATA (A/G). In the present study, a GATA-like
      protein (named as EsGLP) was characterized from Eriocheir sinensis, including an
      834 bp full length open reading frame of EsGLP, encoding a polypeptide of 277
      amino acids. The deduced amino acid sequence of EsGLP contained one conserved
      GATA-type zinc finger of the form Cys-X2-Cys-X17-Cys-X2-Cys, with four cysteine
      sites. The EsGLP mRNA transcripts were mainly detected in the hematopoietic
      tissue, hepatopancreas and gonad. The recombinant EsGLP protein was prepared for
      the antibody production. The EsGLP protein was mainly distributed in the edge of
      lobules in the HPT and the cytoplasm of hemocytes. The mRNA transcripts of EsGLP
      in hemocytes were significantly decreased at 24 h (0.39-fold and 0.27-fold, p <
      .05) and 48 h (0.35-fold and 0.16-fold, p < .05) after LPS and Aeromonas
      hydrophila stimulation, respectively. However, one peak of EsGLP mRNA transcripts
      were recorded at 24 h (8.71-fold, p < .05) in HPT after A. hydrophila
      stimulation. The expression level of EsGLP mRNA in HPT was significantly up
      regulated at 2 h, 2.5 h and 9 h (41.74-fold, 45.38-fold and 26.07-fold, p < .05)
      after exsanguination stimulation. When EsGLP gene expression was inhibited by the
      injection of double-stranded RNA, both the total hemocytes counts and the rate of
      EdU-positive hemocytes were significantly decreased (0.32-fold and 0.56-fold
      compared to that in control group, p < .05). All these results suggested that
      EsGLP was an important regulatory factor in E. sinensis which involved in the
      hemocytes generation and the immune response against invading pathogens.

PMID- 29325713
TI  - The interaction of TAK1 and TAB1 enhances LPS-induced cytokine release via
      modulating NF-kappaB activation (Larimichthys crocea).
AB  - Transforming growth factor-beta-activating kinase 1 (TAK1) is triggered by
      foreign pathogenic infection and involves in proinflammatory response through the
      activation of nuclear factor-kappaB (NF-kappaB), which is specifically regulated
      by TAK1-binding protein 1 (TAB1). However, the expression and regulatory
      characterizations of TAK1 and TAB1 in fish immune response remain largely
      unknown. In the present study, the cDNA sequences of TAK1 (LcTAK1) and TAB1
      (LcTAB1) were identified from large yellow croaker, Larimichthys crocea. The open
      reading frame (ORF) of LcTAK1 was 1725 bp in length, encoding 574 amino acids.
      The putative LcTAK1 protein contained a protein kinase domain and a C-terminal
      coiled-coil region. The ORF of LcTAB1 was 1518 bp encoding 505 amino acids. And a
      typical PP2Cc domain and a conserved sequence motif (PYVDFSQFYLLWGSDH) at C
      terminal were identified in the predicted LcTAB1 protein. Multiple alignments
      showed that LcTAK1 shared 74.0-97.9% and LcTAB1 shared 37.4-95.8% sequence
      identities with TAK1 and TAB1 proteins from other species, respectively.
      Quantitative PCR analysis indicated that both LcTAK1 and LcTAB1 were broadly
      expressed in all examined tissues, with the most predominant expression in brain
      and the weakest expression in muscle, respectively. Subcellular localization
      revealed that both LcTAK1 and LcTAB1 expressed in the cytoplasm. In addition,
      LcTAK1 transcripts increased significantly in LCK cells after flagellin, LPS and
      poly I:C stimulation while LcTAB1 enhanced greatly after LPS and poly I:C
      challenge. Furthermore, the roles of them in NF-kappaB activation were
      investigated by overexpression of LcTAK1 and LcTAB1 in HEK293T cells. Our results
      revealed that NF-kappaB luciferase promoter expression could not be induced by
      overexpression of LcTAK1 or LcTAB1 alone, however, it could be induced by co
      expression of LcTAK1 and LcTAB1 together. Moreover, the roles of LcTAK1 and
      LcTAB1 in immune response analysis showed that NF-kappaB activation enhanced
      significantly in co-overexpressed HEK293T cells following LPS and poly I:C
      stimulation. However, the expression levels of tumor necrosis factor (TNF)-alpha,
      Interleukin-6 (IL-6) and IL-8 were induced only after LPS challenge (p < .05).
      These findings suggested that the TAK1-TAB1 complex of large yellow croaker might
      play an important role in pro-inflammatory cytokines and chemokine release after
      LPS stimulation via inducing NF-kappaB activation.

PMID- 29325714
TI  - Aging-related SUMOylation pattern in the cortex and blood plasma of wild type
      mice.
AB  - Protein activities and mechanisms related to aging has become a growing interest
      nowadays. Since SUMOylation is implicated in several cellular processes, its
      investigation related to senescence, aging and frailty is of high interest. In
      our study, wild type mice cortical lysates, synaptosomes and plasma have been
      processed to evaluate SUMOylation and SUMO machinery expression (Ubc9 and SENP1
      enzymes) profile at different ages. In cortical lysates, SUMO-1ylation reached a
      peak at 6 months followed by a decrease; while in synaptosomes, it progressively
      increased till 18 months. Regarding SUMO-2/3ylation, it was observed a similar
      trend in both lysate and synaptosomes where the protein conjugation was the
      highest at 6 months but interestingly decreased afterwards. In addition, Ubc9 and
      SENP1 enzymes showed a linear increased expression level in both brain
      preparations. Since SUMOylation process is ubiquitously expressed, we were
      interested to identify SUMO conjugation at peripheral level too. Thus, SUMO
      1ylation and SUMO-2/3ylation expression level has been detected in mouse plasma
      that revealed an inverted U-shaped curve trend during mice lifespan.
      Surprisingly, SENP1 enzyme was not present in the plasma while Ubc9 enzyme
      reached a plateau at 6 months and was highly expressed till 18 months. In
      conclusion, our data indicates that SUMOylation is highly correlated with age
      related processes which indisputably need to be considered for further
      investigation.

PMID- 29325715
TI  - Orexin knockout mice exhibit impaired spatial working memory.
AB  - Orexins play a crucial role in the maintenance of arousal and are involved in the
      modulation of diverse physiological process, including cognitive function. Recent
      data have suggested that orexins are involved in learning and memory processes.
      The purpose of this study was to assess the effects of orexin deficiency on
      working memory. A delayed non-matching-to-place T-maze task was used to evaluate
      spatial working memory in mice lacking orexin prepro-peptide (orexin knockout;
      KO) and wild-type controls. We demonstrated that the number of correct choices in
      the orexin KO mice became lower than that of the controls over training. In an
      object exploration task, the controls explored the displaced object more than the
      mutants did, whereas this difference was not observed for the nondisplaced
      objects in either group. The orexin KO mice showed locomotor activity comparable
      to the control mice in terms of total distance traveled across training in both
      the object exploration task and the open field test. These findings indicate that
      the orexin system plays an important role in working memory of spatial cues.

PMID- 29325716
TI  - Corrigendum to "Novel approaches to microbial enhancement of oil recovery" [J.
      Biotechnol. 266 (2018) 118-123].

PMID- 29325717
TI  - Factors related to older patients' fear of falling during the first mobilization
      after total knee replacement and total hip replacement.
AB  - The aim of this study was to determine fear of falling in the first mobilization
      and affecting factors in older patients. The study had a descriptive and cross
      sectional design. Data were collected in Izmir, Turkey between February 2014 and
      March 2016. The sample included 204 older patients undergoing joint replacement
      surgery. Fifty-seven-point four percent and 42.6% of the patients had total hip
      and knee replacement respectively. 42.2% of the patients had a severe fear of
      falling when they were first mobilized. There was a statistically significant
      difference between fear of falling in the first mobilization and the mean pain
      severity. In addition, the difference between fear of falling and the mean
      anxiety level was statistically significant. Pain and anxiety are important
      factors contributing to fear of falling in mobilization. The results of the study
      can help develop multidimensional strategies for reducing fear of falling in
      older people after joint replacement.

PMID- 29325718
TI  - Using story and art to improve education for older patients and their caregivers.

PMID- 29325719
TI  - Is that really worth it - assuring value.

PMID- 29325720
TI  - Development of pancreatic machine perfusion: translational steps from porcine to
      human models.
AB  - BACKGROUND: Hypothermic machine perfusion (HMP) is increasingly being used for
      extended criteria kidney grafts. Pancreatic HMP is challenging because
      physiologically the pancreas is a low-flow organ susceptible to edema. We report
      the successful development of preclinical HMP models using porcine pancreases, as
      well as human pancreases unsuitable for clinical transplantation. METHODS: Ten
      porcine pancreases were used in the development of these perfusion models.
      Pancreases underwent 24 h of static cold storage (SCS, n = 3) and then viability
      assessment on an isolated oxygenated normothermic reperfusion (NRP) circuit or 24
      h SCS, 5 h of HMP, and then NRP (SCS-HMP, n = 3). Human pancreases (n = 3) were
      used in the development of a preclinical model. RESULTS: Porcine HMP demonstrated
      stable perfusion indices at low pressures, with a weight gain of between 15.3%
      and 27.6%. During NRP, SCS-HMP pancreases demonstrated stable perfusion flow
      indices (PFIs) throughout reperfusion (area under the curve was in the range of
      0.49-2.04 mL/min/100 g/mm Hg), whereas SCS-only pancreases had deteriorating PFI
      with a decline of between 19% and 46%. Human pancreas models demonstrated stable
      PFI between 0.18 and 0.69 mL/min/100 g/mm Hg during HMP with weight gain of
      between 3.9% and 14.7%. NRP perfusion in porcine and human models was stable, and
      functional assessment via insulin secretion demonstrated beta cell viability.
      Exocrine function was intact with production of pancreatic secretions only in
      human grafts. CONCLUSIONS: Application of machine perfusion in preclinical
      porcine and human pancreas models is feasible and successful; the development of
      these translational models could be beneficial in improving pancreas preservation
      before transplantation and allowing organ viability assessment and optimization.

PMID- 29325721
TI  - Letter to the Editor concerning the article "Ex vivo heart perfusion after
      cardiocirculatory death; a porcine model".

PMID- 29325724
TI  - Rheumatoid Arthritis, Disease Modifying Agents, and Periprosthetic Joint
      Infection: What Does a Joint Surgeon Need to Know?
AB  - The incidence of periprosthetic joint infection (PJI) among patients with
      rheumatoid arthritis (RA) is 1.6* greater than in patients undergoing the same
      procedure for osteoarthritis. This higher risk "may" be due to the
      immunosuppressive therapies for RA patients including corticosteroids, such as
      prednisone, and disease-modifying antirheumatic drugs (DMARDs), such as
      methotrexate. There is a debate about the role of DMARDs in increasing the
      incidence of subsequent PJI. Studies show conflicting results, with some
      demonstrating no significant increase in the rates of PJI and some finding
      otherwise. The International Consensus Meeting on PJI recommended that DMARDs
      should be halted prior to an elective total joint arthroplasty based on their
      half-life. Moreover, the International Consensus Meeting stated that cessation of
      immunosuppressant medications should be performed in consultation with and under
      the direction of the treating physician. In this review, we aimed to provide an
      introduction to the available treatment options and cover the recommendations on
      the treatment protocols for RA patients who undergo elective total joint
      arthroplasty.

PMID- 29325722
TI  - Effects of siRNA-dependent knock-down of cardiolipin synthase and tafazzin on
      mitochondria and proliferation of glioma cells.
AB  - The mitochondrial phospholipid cardiolipin (CL) has been implicated with
      mitochondrial morphology, function, and cell proliferation. Changes in CL are
      often paralleled by changes in the lipid environment of mitochondria that may
      contribute to mitochondrial function and proliferation. This study aimed to
      separate the effects of CL content and CL composition from cellular free fatty
      acid distribution on bioenergetics and proliferation in C6 glioma cells. To this
      end, cardiolipin synthase and the CL remodelling enzyme, tafazzin, were knocked
      down by siRNA in C6 cells. After 72 h of cultivation, we analysed CL composition
      by means of LC/MS/MS, distribution of cellular fatty acids by means of gas
      chromatography, and determined oxygen consumption and proliferation. Knock-down
      of cardiolipin synthase affected the cellular CL content in the presence of
      linoleic acid (LA) in the culture medium. Knock-down of tafazzin had no
      consequence with respect to the pattern of cellular fatty acids but caused a
      decrease in cell proliferation. It significantly changed the distribution of
      molecular CL species, increased CL content, decreased oxygen consumption, and
      decreased cell proliferation when cultured in the presence of linoleic acid (LA).
      The addition of linoleic acid to the culture medium caused significant changes in
      the pattern of cellular fatty acids and the composition of molecular CL species.
      These data suggest that tafazzin is required for efficient bioenergetics and for
      proliferation of glioma cells. Supplementation of fatty acids can be a powerful
      tool to direct specific changes in these parameters.

PMID- 29325723
TI  - Double function hydroperoxide lyases/epoxyalcohol synthases (CYP74C) of higher
      plants: identification and conversion into allene oxide synthases by site
      directed mutagenesis.
AB  - The CYP74C subfamily of fatty acid hydroperoxide transforming enzymes includes
      hydroperoxide lyases (HPLs) and allene oxide synthases (AOSs). This work reports
      a new facet of the putative CYP74C HPLs. Initially, we found that the recombinant
      CYP74C13_MT (Medicago truncatula) behaved predominantly as the epoxyalcohol
      synthase (EAS) towards the 9(S)-hydroperoxide of linoleic acid. At the same time,
      the CYP74C13_MT mostly possessed the HPL activity towards the 13(S)
      hydroperoxides of linoleic and alpha-linolenic acids. To verify whether this
      dualistic behaviour of CYP74C13_MT is occasional or typical, we also examined
      five similar putative HPLs (CYP74C). These were CYP74C4_ST (Solanum tuberosum),
      CYP74C2 (Cucumis melo), CYP74C1_CS and CYP74C31 (both of Cucumis sativus), and
      CYP74C13_GM (Glycine max). All tested enzymes behaved predominantly as EAS toward
      9-hydroperoxide of linoleic acid. Oxiranyl carbinols such as (9S,10S,11S,12Z)
      9,10-epoxy-11-hydroxy-12-octadecenoic acids were the major EAS products. Besides,
      the CYP74C31 possessed an additional minor 9-AOS activity. The mutant forms of
      CYP74C13_MT, CYP74C1_CS, and CYP74C31 with substitutions at the catalytically
      essential domains, namely the "hydroperoxide-binding domain" (I-helix), or the
      SRS-1 domain near the N-terminus, showed strong AOS activity. These HPLs to AOSs
      conversions were observed for the first time. Until now a large part of CYP74C
      enzymes has been considered as 9/13-HPLs. Notwithstanding, these results show
      that all studied putative CYP74C HPLs are in fact the versatile HPL/EASs that can
      be effortlessly mutated into specific AOSs.

PMID- 29325725
TI  - Who Goes to Inpatient Rehabilitation or Skilled Nursing Facilities Unexpectedly
      Following Total Knee Arthroplasty?
AB  - BACKGROUND: Inpatient rehabilitation facilities (IRFs) and skilled nursing
      facilities (SNFs) represent a significant portion of post-operative expenses of
      bundled payments for total knee arthroplasty (TKA). Although many surgeons no
      longer routinely send patients to IRFs or SNFs, some patients are unable to be
      discharged directly home. This study identified patient factors for discharge to
      post-acute care facilities with an institutional protocol of discharging TKA
      patients home. METHODS: A retrospective review of patients undergoing primary
      unilateral TKA at a single institution from 2012 to 2017 was performed. All
      surgeons discharged patients home as a routine protocol. An electronic query
      followed by manual review identified discharge disposition, demographic factors,
      co-morbidities, and other patient factors. In total, 2281 patients were
      identified, with 9.6% discharged to SNFs or IRFs and 90.4% discharged home.
      Univariate and multivariate analyses were conducted to create 2 predictive models
      for patient discharge: pre-operative visit and hospital course. RESULTS: Among 43
      variables studied, 6 were found to be significant pre-operative risk factors for
      a discharge disposition other than home. In descending order, age 75 or greater,
      female, non-Caucasian race, Medicare status, history of depression, and Charlson
      Comorbidity Index were predictors for patients going to IRFs. In addition, any in
      hospital complications led to a higher likelihood of being discharged to IRFs and
      SNFs. Both models had excellent predictive assessments with area under curve
      values of 0.79 and 0.80 for pre-operative visit and hospital course. CONCLUSION:
      This study identifies pre-operative and in-hospital factors that predispose
      patients to non-routine discharges, which allow surgeons to better predict
      patient post-operative disposition.

PMID- 29325726
TI  - Quality of life disparities between persons with schizophrenia and their
      professional caregivers: Network analysis in a National Cohort.
AB  - BACKGROUND: Disparities between mental health patients and their professional
      caregivers in quality of life appraisals have been identified, however, the
      structure that such disparities assume is unknown. AIMS: To examine the network
      structure of quality of life appraisals and disparities using network analysis.
      METHODS: Participants were 1639 persons with schizophrenia using psychiatric
      rehabilitation services and their primary professional caregivers (N=582).
      Quality of life for persons with schizophrenia was measured based on an
      abbreviated version of the Manchester Short Assessment of Quality of Life.
      Appraisals were made self-reported and by professional caregivers. Disparities
      scores between the aforementioned were computed. Network analysis was performed
      on all quality of life appraisals. Sensitivity analyses were conducted. RESULTS:
      The self-appraised network significantly (p<0.05) differed by network strength
      compared to the caregiver-appraised network. Self-appraised network communities
      (clusters of quality of life items) were health conditions and socioeconomic
      system, whereas caregiver-appraised network communities were social activities,
      and combined socioeconomic and health conditions. Strength centrality was highest
      for self-appraised social status and for caregiver-appraised residential status
      (Z=1.63, Z=1.12, respectively). The disparity scores network clustered into two
      communities: social relations and combined financial and health conditions. The
      most central appraisal disparities were in social status. CONCLUSIONS: Quality of
      life differed when self-appraised by persons with schizophrenia compared to when
      appraised by their professional caregivers, yet the salient role of social
      relations was shared. The latter may be an initial focus of discussion by persons
      with schizophrenia and their caregivers.

PMID- 29325728
TI  - Myo-inositol lowers the risk of developing gestational diabetic mellitus in
      pregnancies: A systematic review and meta-analysis of randomized controlled
      trials with trial sequential analysis.
AB  - AIMS: to explore the potential benefit of myo-inositol on pregnant women with
      high risk of developing gestational diabetes mellitus (GDM). METHODS: Pubmed,
      Embase, and Cochrane library were systematically searched for randomized
      controlled trials (RCTs) comparing myo-inositol with placebo for pregnant women
      with risk factors of GDM. Primary outcome were the incidence of GDM and birth
      weight. Secondary outcomes included fasting, 1h, and 2h oral glucose tolerance
      test (OGTT), and complications. Trial sequential analysis (TSA) was performed on
      primary outcomes to confirm the pooled results. Number needed to treat (NNT) was
      calculated to show the efficacy of myo-inositol supplement. RESULTS: Four RCTs
      with 586 patients were included. Compared with placebo, patients with myo
      inositol supplement had significantly lower the risk of developing GDM (RR=0.44,
      95% CI [0.32, 0.62], P<0.0001) without heterogeneity (I2=0%, P=0.99), which was
      confirmed by TSA. NNT was 6.2 and rounded to 7. Myo-inositol did not
      significantly decrease birth weight (60.60g, 95% CI [-177.21, 56.02], P=0.31)
      with significant heterogeneity (I2=52%, P=0.12), but was not confirmed by TSA.
      Myo-inositol supplement was related to significantly lower fasting, 1h, and 2h
      OGTT value and the incidence of pre-term delivery. Difference was not significant
      between myo-inositol and placebo regarding incidence of other complications.
      CONCLUSION: Myo-inositol is related to lower incidence of GDM, as well as
      fasting, 1h, and 2h OGTT value, in pregnant women with high risk of this
      condition. Myo-inositol might not be related to a lower birth weight, which needs
      further confirmation.

PMID- 29325727
TI  - Low-neurotoxicity anesthesia.

PMID- 29325729
TI  - Amatoxin-Containing Mushroom Poisonings: Species, Toxidromes, Treatments, and
      Outcomes.
AB  - Amatoxins are produced primarily by 3 species of mushrooms: Amanita, Lepiota, and
      Galerina. Because amatoxin poisonings are increasing, the objective of this
      review was to identify all amatoxin-containing mushroom species, present a
      toxidromic approach to earlier diagnoses, and compare the efficacies and outcomes
      of therapies. To meet these objectives, Internet search engines were queried with
      keywords to select peer-reviewed scientific articles on amatoxin-containing
      mushroom poisoning and management. Descriptive epidemiological analyses have
      documented that most mushroom poisonings are caused by unknown mushrooms, and
      most fatal mushroom poisonings are caused by amatoxin-containing mushrooms.
      Amanita species cause more fatal mushroom poisonings than other amatoxin
      containing species, such as Galerina and Lepiota. Amanita phalloides is
      responsible for most fatalities, followed by Amanita virosa and Amanita verna.
      The most frequently reported fatal Lepiota ingestions are due to Lepiota
      brunneoincarnata, and the most frequently reported fatal Galerina species
      ingestions are due to Galerina marginata. With the exception of liver
      transplantation, the current treatment strategies for amatoxin poisoning are all
      supportive and have not been subjected to rigorous efficacy testing in randomized
      controlled trials. All patients with symptoms of late-appearing gastrointestinal
      toxicity with or without false recovery or quiescent periods preceding acute
      liver insufficiency should be referred to centers providing liver
      transplantation. Patients with amatoxin-induced acute liver insufficiency that
      does not progress to liver failure will have a more favorable survival profile
      with supportive care than patients with amatoxin-induced acute liver failure,
      about half of whom will require liver transplantation.

PMID- 29325730
TI  - Use of cardiovascular polypills for the secondary prevention of cerebrovascular
      disease.
AB  - INTRODUCTION: There is little control of cardiovascular (CV) risk factors in
      secondary prevention after an ischaemic stroke, in part due to a lack of
      adherence to treatment. The CV polypill may contribute to proper treatment
      adherence, which is necessary for CV disease prevention. This study aimed to
      establish how and in what cases the CV polypill should be administered. METHODS:
      A group of 8 neurologists drafted consensus recommendations using structured
      brainstorming and based on their experience and a literature review. RESULTS:
      These recommendations are based on the opinion of the participating experts. The
      use of the CV polypill is beneficial for patients, healthcare professionals, and
      the health system. Its use is most appropriate for atherothrombotic stroke,
      lacunar stroke, stroke associated with cognitive impairment, cryptogenic stroke
      with CV risk factors, and silent cerebrovascular disease. It is the preferred
      treatment in cases of suspected poor adherence, polymedicated patients, elderly
      people, patients with polyvascular disease or severe atherothrombosis, young
      patients in active work, and patients who express a preference for the CV
      polypill. Administration options include switching from individual drugs to the
      CV polypill, starting treatment with the CV polypill in the acute phase in
      particular cases, use in patients receiving another statin or an angiotensin ii
      receptor antagonist, or de novo use if there is suspicion of poor adherence.
      Nevertheless, use of the CV polypill requires follow-up on the achievement of the
      therapeutic objectives to make dose adjustments. CONCLUSIONS: This document is
      the first to establish recommendations for the use of the CV polypill in
      cerebrovascular disease, beyond its advantages in terms of treatment adherence.

PMID- 29325731
TI  - Pharmacogenomic Testing in Child and Adolescent Psychiatry: An Evidence-Based
      Review.
AB  - Significant advances have been made in the application of pharmacogenomic testing
      for the treatment of patients with psychiatric disorders. Over the past decade, a
      number of studies have evaluated the utility of pharmacogenomic testing in
      pediatric patients with psychiatric disorders. The evidence base for
      pharmacogenomic testing in youth with depressive and anxiety disorders as well as
      attention/deficit hyperactivity disorder (ADHD) is reviewed in this article.
      General pharmacogenomic principles are summarized and functional polymorphisms in
      P450 enzymes (and associated metabolizer phenotypes), the serotonin transporter
      promoter polymorphisms, serotonin 2A receptor genes (e.g., HT2AR) and
      catecholamine pathway genes (e.g., COMT) are reviewed. These commonly tested
      pharmacogenomic markers are discussed with regard to studies of drug levels,
      efficacy and side effects. The translation of pharmacogenomics to
      individualized/precision medicine in pediatric patients with ADHD, anxiety and
      depressive disorders has accelerated; however, its application remains
      challenging given that there are numerous divergent pathways between
      medication/medication dose and clinical response and side effects. Nonetheless,
      by leveraging variations in individual genes that may be relevant to medication
      metabolism or medication target engagement, pharmacogenomic testing may have a
      role in predicting treatment response, side effects and medication selection in
      youth with ADHD, depressive and anxiety disorders.

PMID- 29325732
TI  - Onchocerciasis associated epilepsy: An important neglected public health problem.

PMID- 29325733
TI  - Associations of GBP2 gene copy number variations with growth traits and
      transcriptional expression in Chinese cattle.
AB  - Copy number variations (CNVs) recently have been recognized as another important
      genetic variability followed single nucleotide polymorphisms (SNPs). The
      guanylate binding protein 2 (GBP2) gene plays an important role in cell
      proliferation. This study was performed to determine the presence of GBP2 CNV
      (relative to Angus cattle) in 466 individuals representing six main cattle breeds
      from China, identify its relationship with growth, and explore the biological
      effects of gene expression. There were two CNV regions in the GBP2 gene, for
      three types, CNV1 loss type (relative to Angus cattle) was more frequent in XN
      than other breeds, and CNV2 loss type (relative to Angus cattle) was more
      frequent in XN and CDM than other breeds. Though the GBP2 gene copy number
      presented no correlation with the transcriptional expression of JX (P > .05), but
      the transcriptional expression in heart is higher than other tissues, and the
      copy number in muscles and fat of JX is higher than others breeds. Statistical
      analysis revealed that the GBP2 gene CNV1 and CNV2 were significantly associated
      with growth traits (P < .05). In conclusion, this research established the
      correlations between CNVs of GBP2 gene and growth traits in different cattle
      breeds, and our results suggested that the CNVs in GBP2 gene may be considered
      markers for the molecular breeding of Chinese beef cattle.

PMID- 29325735
TI  - Whole transcriptome analysis reveals potential novel mechanisms of low-level
      linezolid resistance in Enterococcus faecalis.
AB  - Linezolid is an oxazolidinone antibiotic commonly used to treat serious
      infections caused by vancomycin-resistant enterococcus. Recently, low-level
      linezolid resistant Enterococcus faecalis strains have emerged worldwide, but the
      resistant mechanisms remain undefined. Whole-transcriptome profiling was
      performed on an E. faecalis strain P10748 with low-level linezolid resistance in
      comparison with a linezolid-susceptible strain 3138 and the standard control
      strain ATCC29212. The functions of differentially expressed genes (DEGs) were
      predicted, with some DEGs potentially involved in drug resistance were validated
      by PCR and quantitative PCR (qPCR). RNA-Seq on three E. faecalis strains
      generated 1920 unigenes, with 98% of them assigned to various function groups. A
      total of 150 DEGs were identified in the linezolid resistant strain P10748
      compared to the linezolid susceptible strains 3138 and ATCC29212. Functional
      analysis indicated a significant transcriptomic shift to membrane transportation
      and biofilm formation in strain P10748, with three significantly up-regulated
      DEGs predicted to be associated with drug resistance through active efflux pumps
      and biofilm formation. The existence of these three DEGs was further confirmed by
      PCR and qPCR. The significant upregulation of genes associated with efflux pumps
      and biofilm formation in the linezolid resistant strain suggests their roles in
      low-level resistance to linezolid in E. faecalis.

PMID- 29325734
TI  - Fat mass and obesity-associated gene rs9939609 polymorphism is a potential
      biomarker of recurrent venous thromboembolism in male but not in female patients.
AB  - Multiple genetic variations have been identified in FTO (fat mass and obesity
      associated) gene. Among them, FTO rs9939609 polymorphism is shown to be
      associated with the risk of primary venous thromboembolism (VTE). However, its
      role in recurrent VTE is not known. The aim of our study was to investigate the
      association between FTO rs9939609 polymorphism and the risk of VTE recurrence in
      a prospective follow-up study in both male and female patients. FTO rs9939609
      polymorphism (T/A) was analyzed in the Malmo thrombophilia study (MATS, followed
      for ~10 years) by using TaqMan PCR. MATS patients (n = 1050) were followed from
      the discontinuation of anticoagulant treatment until diagnosis of VTE recurrence
      or the end of follow-up. A total of 126 patients (12%) had VTE recurrence during
      follow-up. Cox regression analyses showed that sex modified the potential effect
      of FTO rs9939609 polymorphism on VTE recurrence. Male patients with the AA
      genotype for the FTO rs9939609 polymorphism had significantly higher risk of VTE
      recurrence as compared to the TT or AT genotypes (univariate hazard ratio [HR] =
      2.05, 95% confidence interval [CI] = 1.2-3.5, P = 0.009 and adjusted HR = 2.03,
      95% CI 1.2-3.6, P = 0.013). There was no association between FTO rs9939609
      polymorphism and VTE recurrence in female patients. In conclusion, our results
      show that FTO rs9939609 polymorphism in recurrent VTE may differ according to
      gender and FTO polymorphism may predict VTE recurrence in male patients.

PMID- 29325736
TI  - Differential association of DENND1A genetic variants with polycystic ovary
      syndrome in Tunisian but not Bahraini Arab women.
AB  - BACKGROUND AND AIM: Polycystic ovary syndrome (PCOS) is a common endocrine
      disorder, and results from interaction between modifiable and non-modifiable
      factors, including genetic predisposition. Previous genome-wide association
      studies and meta-analysis identified DENND1A as PCOS susceptibility locus in
      some, but not all populations. We investigated whether the association of DENND1A
      gene variants with PCOS was similar between Tunisian and Bahraini Arab women.
      SUBJECTS AND METHODS: This was retrospective case-control study. Study subjects
      comprised 320 women with PCOS, and 446 age-and ethnically-matched control women.
      Genotyping of DENND1A rs10818854, rs2479106, and rs10986105 variants was done by
      real-time PCR. RESULTS: Minor allele frequency of rs10818854 and rs10986105
      DENND1A variants were significantly higher among women with PCOS. Setting
      homozygous wild-type genotype carrier as reference, rs10818854 and rs10986105
      were associated with increased risk of PCOS, which persisted after controlling
      for key covariates, while reduced PCOS risk was seen with only rs2479106 under
      the additive model. This assigned PCOS susceptibility and protective nature to
      these genotypes, respectively. Both rs10818854 and rs10986105 were positively
      associated with HOMA-IR and AMH in women with PCOS. Haploview analysis revealed
      limited linkage disequilibrium between the tested DENND1A variants. Extensive
      diversity in haplotypes assignment was seen, with most haplotypes (99.5%)
      captured by 5 haplotypes. Taking GAT haplotype as reference, AAG, and GAG
      haplotypes were positively, while GAT haplotype was negatively associated with
      PCOS. CONCLUSION: The association of DENND1A rs10818854 and rs10986105 variants
      with PCOS in Tunisian but not Bahraini women confirms the dependence of this
      association on the ethnic/racial origin of study subjects.

PMID- 29325737
TI  - Reliability and validity of the Chinese version neuropathic pain symptom
      inventory in patients with colorectal cancer.
AB  - BACKGROUND/PURPOSE: Chemotherapy-induced peripheral neuropathy is a common
      consequence of chemotherapeutic treatments in patients with cancer. This study
      evaluated the validity and reliability of a Chinese version of the Neuropathic
      Pain Symptom Inventory (C-NPSI) in patients with colorectal cancer and
      chemotherapy-induced peripheral neuropathy. METHODS: This cross-sectional study
      recruited 106 patients from a cancer center in Northern Taiwan. The C-NPSI was
      obtained through the translation and back-translation of the original NPSI.
      Content validity was evaluated by 10 experts. Internal consistency reliability
      was assessed through Pearson correlation analysis. Construct validity was
      conducted by confirmed factor analysis. Convergent validity was examined using
      the Chinese version of Profile of Mood States-Short Form (POMS-SF). RESULTS: The
      item-level and average scale-level content validity indices were 0.80 and 0.90,
      respectively. Internal consistency reliability was acceptable (Cronbach's alpha
      coefficient = 0.9). A parsimonious goodness-of-fit model was supported by the
      normed chi-square (x2/df = 2.74), root mean square error of approximation (RMSEA;
      0.10) and root mean square error with respect to the mean (RMSEM; 0.126, 90%
      confidence interval [CI], 0.093-0.16); partial indices were acceptable (goodness
      of-fit index [GFI] = 0.90; comparative fit index [CFI] = 0.89; incremental fit
      index [IFI] = 0.90). Additional model modifications demonstrated goodness of fit
      (x2/df = 1.78; RMSEA = 0.08; RMSEM = 0.085, 90% CI, 0.041-0.12; GFI = 0.92; CFI =
      0.96; IFI = 0.96). Convergent validity showed most coefficients between the C
      NPSI and POMS-SF Chinese version have a significant positive correlation (p <
      0.05-0.005). CONCLUSION: The C-NPSI has satisfactory reliability and validity.
      Clinicians and physician can use it to evaluate and manage oxaliplatin-induced
      peripheral neuropathy.

PMID- 29325738
TI  - The Effect of Patient and Surgical Characteristics on Renal Function After
      Partial Nephrectomy.
AB  - BACKGROUND: The purpose of the study was to identify patient and disease
      characteristics that have an adverse effect on renal function after partial
      nephrectomy. PATIENTS AND METHODS: We conducted a retrospective review of 387
      patients who underwent partial nephrectomy for renal tumors between 2006 and
      2014. A line plot with a locally weighted scatterplot smoothing was generated to
      visually assess renal function over time. Univariable and multivariable
      longitudinal regression analyses incorporated a random intercept and slope to
      evaluate the association between patient and disease characteristics with renal
      function after surgery. RESULTS: Median age was 60 years and most patients were
      male (255 patients [65.9%]) and white (343 patients [88.6%]). In univariable
      analysis, advanced age at surgery, larger tumor size, male sex, longer ischemia
      time, history of smoking, and hypertension were significantly associated with
      lower preoperative estimated glomerular filtration rate (eGFR). In multivariable
      analysis, independent predictors of reduced renal function after surgery included
      advanced age, lower preoperative eGFR, and longer ischemia time. Length of time
      from surgery was strongly associated with improvement in renal function among all
      patients. CONCLUSION: Independent predictors of postoperative decline in renal
      function include advanced age, lower preoperative eGFR, and longer ischemia time.
      A substantial number of subjects had recovery in renal function over time after
      surgery, which continued past the 12-month mark. These findings suggest that
      patients who undergo partial nephrectomy can experience long-term improvement in
      renal function. This improvement is most pronounced among younger patients with
      higher preoperative eGFR.

PMID- 29325739
TI  - Anti-Programmed Cell Death 1/Ligand 1 (PD-1/PD-L1) Antibodies for the Treatment
      of Urothelial Carcinoma: State of the Art and Future Development.
AB  - Immunotherapy with programmed cell death 1/ligand 1 (PD-1/PD-L1) checkpoint
      inhibitors has expanded a previously limited pool of effective treatment options
      for patients with metastatic urothelial carcinoma, particularly those with
      recurring or refractory disease and those who are ineligible for cisplatin. This
      review reports key findings from completed and ongoing clinical trials that
      highlight the potential of PD-1/PD-L1 blockade in urothelial carcinoma. A
      literature search was performed of PubMed, Embase, ClinicalTrials.gov, and
      selected annual congress abstracts. Prospective studies, reviews, editorials, and
      descriptions of ongoing anti-PD-1/PD-L1 studies in bladder cancer were included.
      Anti-PD-1/PD-L1 monoclonal antibodies have shown efficacy and safety across
      patient subgroups with urothelial carcinoma, including those with poor prognostic
      factors. Efficacy was similar across different anti-PD-1/PD-L1 agents. Although
      these antibodies have demonstrated durable responses in a subset of patients with
      urothelial carcinoma, clinicians are currently unable to predict which patients
      may derive benefit from immune checkpoint blockade. Anti-PD-1/PD-L1 antibodies
      have shown favorable clinical activity and tolerability in patients with
      metastatic urothelial carcinoma refractory to platinum-based therapy or who are
      ineligible for cisplatin. The activity of PD-1/PD-L1 inhibitors is now also being
      studied as first-line monotherapy in cisplatin-eligible patients in combination
      with chemotherapy as maintenance therapy after first-line chemotherapy, and in
      earlier disease states, such as muscle-invasive and non-muscle-invasive bladder
      cancer. Better predictive tools to define target patient populations are needed,
      as are further investigations to define optimal combinations or sequencing of
      treatments.

PMID- 29325741
TI  - Functional engineered mesenchymal stem cells with fibronectin-gold composite
      coated catheters for vascular tissue regeneration.
AB  - Vascularization of engineered tissues remains one of the key problems. Here, we
      described a novel approach to promote vascularization of engineered tissues using
      fibronectin (FN) incorporated gold nanoparticles (AuNP) coated onto catheters
      with mesenchymal stem cells (MSCs) for tissue engineering. We found that the FN
      AuNP composite with 43.5 ppm of AuNP exhibited better biomechanical properties
      and thermal stability than pure FN. FN-AuNP composites promoted MSC proliferation
      and increased the biocompatibility. Mechanistically, vascular endothelial growth
      factor (VEGF) promoted MSC migration on FN-AuNP through the endothelial oxide
      synthase (eNOS)/metalloproteinase (MMP) signaling pathway. Vascular femoral
      artery tissues isolated from the implanted FN-AuNP-coated catheters with MSCs
      expressed substantial CD31 and alpha-smooth muscle actin (alpha-SMA), displayed
      higher antithrombotic activity, as well as better endothelialization ability than
      those coated with all other materials. These data suggested that the implantation
      of FN-AuNP-coated catheter with MSCs could be a novel strategy for vascular
      biomaterials applications.

PMID- 29325740
TI  - Indocyanine green loaded hyaluronan-derived nanoparticles for fluorescence
      enhanced surgical imaging of pancreatic cancer.
AB  - Pancreatic ductal adenocarcinoma is highly lethal and surgical resection is the
      only potential curative treatment for the disease. In this study, hyaluronic acid
      derived nanoparticles with physico-chemically entrapped indocyanine green, termed
      NanoICG, were utilized for intraoperative near infrared fluorescence detection of
      pancreatic cancer. NanoICG was not cytotoxic to healthy pancreatic epithelial
      cells and did not induce chemotaxis or phagocytosis, it accumulated significantly
      within the pancreas in an orthotopic pancreatic ductal adenocarcinoma model, and
      demonstrated contrast-enhancement for pancreatic lesions relative to non-diseased
      portions of the pancreas. Fluorescence microscopy showed higher fluorescence
      intensity in pancreatic lesions and splenic metastases due to NanoICG compared to
      ICG alone. The in vivo safety profile of NanoICG, including, biochemical,
      hematological, and pathological analysis of NanoICG-treated healthy mice,
      indicates negligible toxicity. These results suggest that NanoICG is a promising
      contrast agent for intraoperative detection of pancreatic tumors.

PMID- 29325742
TI  - Mutation of the conserved G66 residue in GS region decreased structural stability
      and activity of arginine kinase.
AB  - Arginine kinase (AK) catalyzes the reversible phosphorylation of arginine by ATP,
      yielding the phosphoarginine. Amino acid residues in the guanidine specificity
      (GS) region play important roles in the guanidine-recognition. However, little is
      known about roles of amino acid residue G66 in the GS region in proteins folding,
      activity and structural stability. In this study, a series of G66 mutations were
      constructed to investigate its roles in AK's structural stability and activity.
      Our studies revealed that mutations in this conserved site could cause pronounced
      loss of activity, conformational changes and structural stability. Spectroscopic
      experiments indicate that G66 mutations influences AK transition from the molten
      globule intermediate to the native state in folding process. These results
      provided herein may suggest that amino acid residue G66 may play a relatively
      important role in AK's activity and structural stability.

PMID- 29325743
TI  - Total fractionation and characterization of the water-soluble polysaccharides
      isolated from Enteromorpha intestinalis.
AB  - Water-soluble crude polysaccharides (WE) were extracted from the Enteromorpha
      intestinalis with hot water and further fractionated on a DEAE-52 Cellulose
      chromatography column and Sepharose CL-6B gel-permeation chromatography to afford
      one neutral fraction (WE-11) and five acidic fractions (WE-21, WE-31, WE-32, WE
      41 and WE-42). Monosaccharide analysis showed that WE-32, WE-41 and WE-42 were
      all composed of Rha and GlcA, WE-21 and WE-31 contained Man and Rha, and WE-11
      was composed of GlcA and Xyl. The molecular weight of WE-11, WE-21, WE-31 WE-32,
      WE-41 and WE-42 were 2.23 * 105, 1.42 * 105, 1.42 * 105, 2.62 * 104, 2.23 * 105
      and 8.09 * 104, respectively. Then, antioxidant activities in vitro were
      investigated on the basis of DPPH radical assay, reducing power assay, hydroxyl
      radical assay and superoxide radical assay. Of all polysaccharides fractions, WE
      32 and WE-41 had relative higher content of sulfate and GlcA. In addition, WE-32
      and WE-41 showed relative stronger antioxidant activity and inhibitory activity
      in vitro. The antioxidant activities of polysaccharides were not a function of a
      single factor but a combination of several factors, such as monosaccharide
      composition, molecular weights, protein content, uronic acid and sulfate content.

PMID- 29325744
TI  - Dextran hydrogels by crosslinking with amino acid diamines and their viscoelastic
      properties.
AB  - Amine functionalized polysaccharide hydrogels such as those based on chitosan are
      widely examined as biomaterials. Here we set out to develop a facile procedure
      for developing such hydrogels by crosslinking dextran with amino acid diamines.
      The dextran-amino acid gels were formed by the addition of the amino acid
      diamines to a dextran and epichlorohydrin solution once it became homogeneous.
      This was demonstrated with three amino acid diamines, lysine, lysine methyl
      ester, and cystine dimethyl ester. Hydrogel networks with albumin entrapped were
      also demonstrated. These hydrogels were characterized by FTIR, SEM, rotational
      rheometry, swelling studies and cell biocompatibility analysis. These hydrogels
      showed the unexpected pH-responsive behavior of greater swelling at more basic
      pH, similar to that of an anionic hydrogel. This is uncharacteristic for amine
      functionalized gels as they typically exhibit cationic hydrogel behavior. All
      hydrogels showed similar biocompatibility to that of dextran crosslinked without
      amino acids.

PMID- 29325745
TI  - Chitosan nanoparticles/cellulose nanocrystals nanocomposites as a carrier system
      for the controlled release of repaglinide.
AB  - The aim of the present work was to study the use of cellulose nanocrystals (CNC)
      and chitosan nanoparticles (CHNP) for developing controlled-release drug delivery
      system of the anti-hyperglycemic drug Repaglinide (RPG). CNC was isolated from
      palm fruit stalks by sulfuric acid hydrolysis; the dimensions of the isolated
      nanocrystals were 86-237 nm in length and 5-7 nm in width. Simple and economic
      method was used for the fabrication of controlled release drug delivery system
      from CNC and CHNP loaded with RPG drug via ionic gelation of chitosan in the
      presence of CNC and RPG. The prepared systems showed high drug encapsulation
      efficiency of about ~98%. Chemical modification of CNC by oxidation to introduce
      carboxylic groups on their surface (OXCNC) was also carried out for further
      controlling of RPG release. Particles size analysis showed that the average size
      of CHNP was about 197 nm while CHNP/CNC/RPG or CHNP/OXCNC/RPG nanoparticles
      showed average size of 215-310 nm. Compatibility studies by Fourier transform
      infrared (FTIR) spectroscopy showed no chemical reaction between RPG and the
      system's components used. By studying the drug release kinetic, all the prepared
      RPG formulations followed Higuchi model, indicating that the drug released by
      diffusion through the nanoparticles polymeric matrix.

PMID- 29325746
TI  - First report of the characterization of a snake venom apyrase (Ruviapyrase) from
      Indian Russell's viper (Daboia russelii) venom.
AB  - A novel apyrase from Russell's viper venom (RVV) was purified and characterized,
      and it was named Ruviapyrase (Russell's viper apyrase). It is a high molecular
      weight (79.4 kDa) monomeric glycoprotein that contains 2.4% neutral sugars and
      58.4% N-linked oligosaccharides and strongly binds to Concanavalin A. The LC
      MS/MS analysis did not identify any protein in NCBI protein database,
      nevertheless some de novo sequences of Ruviapyrase showed putative conserved
      domain of apyrase superfamily. Ruviapyrase hydrolysed adenosine triphosphate
      (ATP) to a significantly greater extent (p < .05) as compared to adenosine
      diphosphate (ADP); however, it was devoid of 5'-nucleotidase and
      phosphodiesterase activities. The Km and Vmax values for Ruviapyrase towards ATP
      were 2.54 MUM and 615 MUM of Pi released min-1, respectively with a turnover
      number (Kcat) of 24,600 min-1. Spectrofluorometric analysis demonstrated
      interaction of Ruviapyrase with ATP and ADP at Kd values of 0.92 nM and 1.25 nM,
      respectively. Ruviapyrase did not show cytotoxicity against breast cancer (MCF-7)
      cells and haemolytic activity, it exhibited marginal anticoagulant and strong
      antiplatelet activity, and dose-dependently reversed the ADP-induced platelet
      aggregation. The catalytic activity and platelet deaggregation property of
      Ruviapyrase was significantly inhibited by EDTA, DTT and IAA, and neutralized by
      commercial monovalent and polyvalent antivenom.

PMID- 29325747
TI  - Synthesis, characterization of novel chitosan based water dispersible
      polyurethanes and their potential deployment as antibacterial textile finish.
AB  - Our current research work comprised of synthesis of a series of novel chitosan
      based water dispersible polyurethanes. The synthesis was carried out in three
      steps, in first step, the NCO end capped PU-prepolymer was formed through the
      reaction between Polyethylene glycol (PEG) (Mn = 600), Dimethylolpropionic acid
      (DMPA) and Isophorone diisocyanate (IPDI). In second step, the neutralization
      step was carried out by using Triethylamine (TEA) which resulted the formation of
      neutralized NCO terminated PU-prepolymer, after that the last step chain
      extension was performed by the addition of chitosan and followed the formation of
      dispersion by adding calculated amount of water. The proposed structure of CS
      WDPUs was confirmed by using FTIR technique. The antimicrobial activities of the
      plain weave poly-cotton printed and dyed textile swatches after application of CS
      WDPUs were also evaluated. The results showed that the chitosan incorporation in
      to PU backbone has markedly enhanced the antibacterial activity of WDPUs. These
      synthesized CS-WDPUs are eco-friendly antimicrobial finishes (using natural
      bioactive agents such as chitosan) with potential applications on
      polyester/cotton textiles.

PMID- 29325748
TI  - Cranberry proanthocyanidin-chitosan hybrid nanoparticles as a potential inhibitor
      of extra-intestinal pathogenic Escherichia coli invasion of gut epithelial cells.
AB  - Chitosan interacts with proanthocyanidins through hydrogen-bonding, which allows
      encapsulation and development of stable nanoparticles via ionotropic gelation.
      Cranberry proanthocyanidins (PAC) are associated with the prevention of urinary
      tract infections and PAC inhibit invasion of gut epithelial cells by extra
      intestinal pathogenic Escherichia coli (ExPEC). We determined the effect of
      cranberry proanthocyanidin-chitosan hybrid nanoparticles (PAC-CHTNp) on the ExPEC
      invasion of gut epithelial cells in vitro. PAC-CHTNp were characterized according
      to size, morphology, and bioactivity. Results showed a decrease in the size of
      the nanoparticles as the concentration of PAC was increased, indicating that PAC
      increases cross-linking by hydrogen-bonding on the surface of the chitosan
      nanoparticles. Nanoparticles were produced with diameters ranging from 367.3 nm
      to 293.2 nm. Additionally, PAC-CHTNp significantly inhibited the ability of ExPEC
      to invade the enterocytes by ~80% at 66 MUg GAE/mL and by ~92% at 100 MUg GAE/mL.
      Results also indicate that chitosan nanoparticles alone were not significantly
      different from controls in preventing ExPEC invasion of enterocytes (data not
      shown) and also there were not significant differences between PAC alone and PAC
      CHTNp, suggesting that the new PAC-CHTNp could lead to an increase in the
      stability of encapsulated PAC, maintain the molecular adhesion of PAC to ExPEC.

PMID- 29325749
TI  - Sustained improvement of psoriasis associated with HCV after virologic response
      to sofosbuvir/ribavirin.
AB  - An 18 year old boy attended a dermatology clinic outside our hospital and
      diagnosed with psoriasis. His skin lesions over both ankles (Fig. 1) did not
      improve at all with potent local steroids twice for 3 months, then 3 times daily
      for another 3 months. His dermatologist talked to him about using methotrexate
      and asked for liver function tests before starting the systemic therapy. His ALT
      and AST were doubled. The patient came to our Hepatology clinic worried about his
      elevated liver enzymes. We asked for viral markers. His HCV-Ab was positive, and
      PCR for HCV-RNA was 650,000 IU/ml. Treatment started with sofosbuvir 400 mg PO
      once daily plus ribavirin 600 mg at the morning and 400 mg at the evening. After
      4 weeks, ALT and AST decreased to normal and PCR for HCV-RNA was <5 IU/ml. All
      other lab tests were unremarkable. The skin lesions improved markedly (Fig. 2).
      Now, after 6 months of the end of treatment, sustained virologic response was
      documented and the skin lesions are almost disappeared without any topical or
      systemic treatment.

PMID- 29325750
TI  - Double-balloon enteroscopy (DBE) in patients presenting with obscure
      gastrointestinal bleeding (OGIB).
AB  - BACKGROUND AND STUDY AIMS: Obscure gastrointestinal bleeding (OGIB) is defined as
      bleeding of unknown origin that persists or recurs after an initial negative
      investigation. Identifying the source of OGIB represents a diagnostic challenge
      that is frequently focused on visualizing the small intestine. Conventional
      diagnostic methods, such as push enteroscopy, small-bowel follow-through,
      radionuclide scanning, and angiography, each exhibit inherent limitations. Double
      balloon enteroscopy (DBE) was designed specifically to evaluate the entire small
      bowel. DBE allows for better visualization, biopsy of the identified lesions and
      application of therapeutic techniques. This study sought to assess the role of
      DBE in the diagnosis and management of patients with OGIB. PATIENTS AND METHODS:
      This prospective study was conducted to analyse data from 31 patients presenting
      with OGIB referred for DBE in the Endoscopy Unit at the Internal Medicine
      Department of the Faculty of Medicine, Cairo University. RESULTS: Five patients
      had lesions in locations other than the small intestine that accounted for GI
      bleeding. Thus, the potential source of OGIB was defined as the small intestine
      in 18 of 26 patients (69.2%), and negative DBE findings were noted in eight
      patients (30.8%). Major findings included small intestinal tumours in eight
      patients, vascular bleeding lesions in 8 patients and ulcerations in 2 patients.
      Endoscopic haemostasis was performed in eight patients with vascular lesions. The
      three patients with Petuz-Jegher syndrome underwent polypectomy of their major
      polyps. Patients with gastrointestinal tumours were referred for surgery.
      CONCLUSION: DBE is an excellent endoscopic procedure that has a relatively high
      diagnostic and therapeutic yield. The procedure is feasible and exhibits a high
      safety profile with a low complication rate when performed by an experienced
      endoscopist.

PMID- 29325751
TI  - A difficult diagnosis of coeliac disease: Repeat duodenal histology increases
      diagnostic yield in patients with concomitant causes of villous atrophy.
AB  - Villous atrophy in absence of coeliac disease (CD)-specific antibodies represents
      a diagnostic dilemma. We report a case of a woman with anaemia, weight loss and
      diarrhoea with an initial diagnosis of seronegative CD and a histological
      documented villous atrophy who did not improve on gluten-free diet due to the
      concomitant presence of common variable immunodeficiency (CVID) and Giardia
      lamblia infection. This case report confirms that CD diagnosis in CVID patients
      is difficult; the combination of anti-endomysial antibodies (EmA-IgA), anti
      tissue transglutaminase antibodies (tTG-IgAb) antibodies and total IgA is
      obligatory in basic diagnostic of CD but in CVID are negative. Furthermore, the
      typical histological aspects of the intestinal mucosa in CVID (absence of plasma
      cells and switch to the IgD immunoglobulins), cannot rule out a concomitant CD
      diagnosis. HLA typing in this setting has a low positive predictive value but
      should be considered. Histological response to a gluten-free diet on repeat
      biopsy and the concomitant treatment of other causes of villous atrophy leads to
      a definite diagnosis of CD.

PMID- 29325752
TI  - Body temperature in sepsis: a hot topic.

PMID- 29325754
TI  - A comprehensive approach for evaluating charge heterogeneity in biosimilars.
AB  - Charge heterogeneity is often evaluated during biosimilar development as it is a
      universal feature of monoclonal antibodies (mAbs). A common approach in the
      industry is to develop a biosimilar product with a similar overall charge profile
      as the reference product. However, uncertainty remains with this approach as the
      same charge profile in two different products may be caused by different
      mechanisms. In this work, we present a comprehensive investigation of the charge
      variants of a therapeutic monoclonal antibody and its biosimilar candidate. Not
      only did the candidate show a similar charge profile as the reference product,
      our studies revealed that the same factors contributed to the charge variants of
      the reference product and the biosimilar candidate. We believe our cause-based
      approach mitigates the risks associated with the profile-based method and is a
      rational approach for the charge evaluation of biosimilars.

PMID- 29325755
TI  - Amphotericin B-albumin conjugates: Synthesis, toxicity and anti-fungal activity.
AB  - Amphotericin B (AmB), a hydrophobic drug with negligible aqueous solubility was
      conjugated to bovine serum albumin (BSA) via amide bond coupling to give 6 to 8
      wt% drug payload. The resulting conjugate was characterized using SDS-PAGE and UV
      visible, FTIR and CD spectroscopy. The conjugate was water-soluble to the extent
      of 150 mg/ml, was non-toxic to HEK 293 T cells at a concentration of 500 MUg/ml
      (equivalent to ~30 MUg AmB) and showed hemolysis of <5% at 200 MUg/ml (equivalent
      to ~12 MUg AmB) against human erythrocytes in vitro. In vitro release studies at
      37  degrees C demonstrated steady release of AmB up to 20% from the conjugate
      with little burst effect in phosphate buffered saline whereas thrice the amount
      was released in human plasma in 72 h. AmBisome(r) used as a reference showed a
      very similar release profile in plasma. The conjugate exhibited potential anti
      fungal activity against yeast strains such as C. albicans, C. neoformans and C.
      parapsilosis with the minimum inhibitory concentration (MIC) equivalent to AmB
      ranging from 0.7 to 1.1 MUg/ml while AmBisome(r) and AmB alone showed the MIC
      between 0.78 and 1.5 and 0.53-0.78 MUg/ml respectively. Although AmB has been
      conjugated to various natural and synthetic polymers to improve its solubility
      and reduce its toxicity, the results obtained in this study using the model
      protein BSA as a carrier point to the possibility of taking this pro-drug
      approach to human clinical use using human serum albumin (HSA) as the carrier,
      since HSA has emerged as a versatile drug carrier for treating diabetes and
      cancer and improving the pharmacokinetic profile of many drugs with US FDA
      approving HSA as a drug carrier for the anti-cancer drug paclitaxel (Abraxane(r))
      for human use.

PMID- 29325756
TI  - ?

PMID- 29325757
TI  - The role of fatty acids and their endocannabinoid-like derivatives in the
      molecular regulation of appetite.
AB  - Intake, absorption and synthesis of fatty acids, including those produced by the
      intestinal microbiota are tightly monitored via specific receptors and,
      indirectly through their conversion into a variety of signalling molecules. The
      resulting information is integrated and translated to different physiological
      processes, including the regulation of appetite and satiation. Direct
      chemosensing of fatty acids takes place via interaction with free fatty acid
      (FFA) and other receptors. These are present in the oronasal cavity and along the
      entire gastrointestinal tract, in various other tissues, and, for some receptors
      also in brain. Results from early studies have suggested differences between
      fatty acids in their ability to induce the release of satiety hormones or their
      short-term effects on food-intake. However, more recent findings indicate that
      this has limited impact on long-term energy intake. Similarly, pharmacological
      strategies for appetite control via modulation of peripheral fatty acid binding
      receptors have not met their expectations. Regarding the psychobiology of eating
      behaviour, there has been a shift towards emphasising the importance of food
      reward and the cephalic phase response. Lipid-rich foods are highly energy dense.
      During evolution this has stimulated the development of reward mechanisms, in
      which fatty acids, in conjunction with carbohydrates, are major triggers. Fatty
      acids are also precursors of endocannabinoids and their structural congeners. The
      endocannabinoid system (ECS) plays a pivotal role in the homeostatic and non
      homeostatic regulation of eating behaviour. In the brain it links to different
      endocrine and neuronal pathways, including dopaminergic circuits in the
      mesocorticolimbic system such as the ventral tegmental area and the nucleus
      accumbens, which are crucial for hedonic eating. Despite the vast progress made
      in the field of neurobiology it is clear that eating behaviour, one of our
      strongest instincts, still possess major scientific challenges. The failure,
      already a decade ago, of the cannabinoid-receptor type 1 (CB1) blockers for
      treatment of overweight and its complications may serve as an illustration that
      'single-target' approaches to modulate, or even understand-, over- or undereating
      are very unrealistic.

PMID- 29325753
TI  - Induced hypothermia in patients with septic shock and respiratory failure (CASS):
      a randomised, controlled, open-label trial.
AB  - BACKGROUND: Animal models of serious infection suggest that 24 h of induced
      hypothermia improves circulatory and respiratory function and reduces mortality.
      We tested the hypothesis that a reduction of core temperature to 32-34 degrees C
      attenuates organ dysfunction and reduces mortality in ventilator-dependent
      patients with septic shock. METHODS: In this randomised, controlled, open-label
      trial, we recruited patients from ten intensive care units (ICUs) in three
      countries in Europe and North America. Inclusion criteria for patients with
      severe sepsis or septic shock were a mean arterial pressure of less than 70 mm
      Hg, mechanical ventilation in an ICU, age at least 50 years, predicted length of
      stay in the ICU at least 24 h, and recruitment into the study within 6 h of
      fulfilling inclusion criteria. Exclusion criteria were uncontrolled bleeding,
      clinically important bleeding disorder, recent open surgery, pregnancy or
      breastfeeding, or involuntary psychiatric admission. We randomly allocated
      patients 1:1 (with variable block sizes ranging from four to eight; stratified by
      predictors of mortality, age, Acute Physiology and Chronic Health Evaluation II
      score, and study site) to routine thermal management or 24 h of induced
      hypothermia (target 32-34 degrees C) followed by 48 h of normothermia (36-38
      degrees C). The primary endpoint was 30 day all-cause mortality in the modified
      intention-to-treat population (all randomly allocated patients except those for
      whom consent was withdrawn or who were discovered to meet an exclusion criterion
      after randomisation but before receiving the trial intervention). Patients and
      health-care professionals giving the intervention were not masked to treatment
      allocation, but assessors of the primary outcome were. This trial is registered
      with ClinicalTrials.gov, number NCT01455116. FINDINGS: Between Nov 1, 2011, and
      Nov 4, 2016, we screened 5695 patients. After recruitment of 436 of the planned
      560 participants, the trial was terminated for futility (220 [50%] randomly
      allocated to hypothermia and 216 [50%] to routine thermal management). In the
      hypothermia group, 96 (44.2%) of 217 died within 30 days versus 77 (35.8%) of 215
      in the routine thermal management group (difference 8.4% [95% CI -0.8 to 17.6];
      relative risk 1.2 [1.0-1.6]; p=0.07]). INTERPRETATION: Among patients with septic
      shock and ventilator-dependent respiratory failure, induced hypothermia does not
      reduce mortality. Induced hypothermia should not be used in patients with septic
      shock. FUNDING: Trygfonden, Lundbeckfonden, and the Danish National Research
      Foundation.

PMID- 29325758
TI  - MiR-186-5p upregulation inhibits proliferation, metastasis and epithelial-to
      mesenchymal transition of colorectal cancer cell by targeting ZEB1.
AB  - MicroRNA-186-5p (miR-186-5p) is upregulated and exhibits as a crucial oncogene in
      various human tumors. However, the functions and underlying mechanisms of this
      microRNA on colorectal cancer remain largely unknown. Here, we report that miR
      186-5p share a lower expression in colorectal cancer cell lines (HT116, H29,
      SW620 and LoVo) than in normal colonic epithelial cell line NCM460. MiR-186-5p
      overexpression inhibits proliferation, metastasis and epithelial-to-mesenchymal
      transition (EMT) of colorectal cancer cell line LoVo. Zinc Finger E-Box Binding
      Homeobox 1 (ZEB1), an EMT related marker, is predicted as a target of miR-186-5p.
      Luciferase reporter assay, qRT-PCR and western blot analysis showed that miR-186
      5p directly targeted the 3'-untranslated regions (3'UTR) of ZEB1 messenger RNA.
      Further functional experiments indicated that overexpression of miR-186-5p
      suppress the proliferation and metastasis ability of LoVo, which was consistent
      with the inhibitory effects by knockdown of ZEB1. Additionally, overexpression of
      ZEB1 could significantly reverse the miR-186-5p mimics initiated suppression
      impact of proliferation, metastasis and EMT on LoVo. In summary, miRNA-186-5p
      affects the proliferation, metastasis and EMT process of colorectal cancer cell
      by inhibition of ZEB1. Hence, it may serve as a promising therapeutic target for
      colorectal cancer.

PMID- 29325759
TI  - SNPs in the vicinity of P2X7R, RANK/RANKL/OPG and Wnt signalling pathways and
      their association with bone phenotypes in academy footballers.
AB  - CONTEXT: Genotype plays an important role in influencing bone phenotypes, such as
      bone mineral density, but the role of genotype in determining responses of bone
      to exercise has yet to be elucidated. OBJECTIVE: To determine whether 10 SNPs
      associated with genes in the vicinity of P2X7R, RANK/RANKL/OPG and Wnt Signalling
      Pathways are associated with bone phenotypes in elite academy footballers (Soccer
      players) and to determine whether these genotypes are associated with training
      induced changes in bone. Design, participants, and methods: 99 elite academy
      footballers volunteered to participate. Peripheral computed tomography of the
      tibia (4%, 14%, 38% and 66% sites) was performed immediately before and 12 weeks
      after an increase in football training volume. Genotypes were determined using
      proprietary fluorescence-based competitive allele-specific PCR assays. RESULTS:
      No significant genotype by time interactions were shown for any of the SNPs
      analysed (P > .05). A main effect of genotype was shown. SOST SNP rs1877632
      (trabecular density), P2X7R SNPs rs1718119 (cortical thickness and CSA),
      rs3751143 (SSI, CSA, cortical CSA and periosteal circumference) RANK/RANKL/OPG
      SNPs rs9594738 (periosteal circumference), rs1021188 (cortical thickness and CSA)
      and rs9594759 (cortical density) were associated with bone phenotypes (P < .05).
      CONCLUSIONS: No association was shown between P2X7R, RANK/RANKL/OPG and Wnt
      Signalling SNPs and a change in bone phenotypes following 12 weeks of increased
      training volume in elite academy footballers. However, SNPs were associated with
      bone phenotypes pre training. These data highlight the complexity of the
      interaction between SNPs in the vicinity of the RANK/RANKL/OPG, P2X7R and Wnt
      metabolic regulatory pathways and bone phenotypes in elite academy footballers.

PMID- 29325760
TI  - NephMadness After 5 Years: A Recap and Game Plan for the Future.

PMID- 29325761
TI  - Trends in Utilization of Robotic and Open Partial Nephrectomy for Management of
      cT1 Renal Masses.
AB  - BACKGROUND: Partial nephrectomy is widely used for surgical management of small
      renal masses. Use of robotic (RPN) versus open partial nephrectomy (OPN) among
      various populations is not well characterized. OBJECTIVE: To analyze trends in
      utilization of RPN and disparities that may be associated with this procedure for
      management of cT1 renal masses in the USA. DESIGN, SETTING, AND PARTICIPANTS:
      Patients who underwent RPN or OPN for clinical stage T1N0M0 renal masses in the
      USA from 2010 to 2013 were identified in the National Cancer Data Base. A total
      of 23 154 patients fulfilled the inclusion criteria. OUTCOME MEASUREMENTS AND
      STATISTICAL ANALYSIS: Univariable and multivariable logistic regression analyses
      were performed to evaluate differences in receiving RPN or OPN across various
      patient groups. RESULTS AND LIMITATIONS: Utilization of RPN increased from 41% in
      2010 to 63% in 2013. Black patients (adjusted odds ratio [aOR] 0.91, 95%
      confidence interval [CI] 0.84-0.98) and Hispanic patients (aOR 0.85, 95% CI 0.77
      0.95) were less likely to undergo RPN. RPN was less likely to be performed in
      rural counties (aOR 0.80, 95% CI 0.66-0.98) and in patients with no insurance
      (aOR 0.52, 95% CI 0.44-0.61) or patients covered by Medicaid (aOR 0.81, 95% CI
      0.73-0.90). There was no significant difference in RPN utilization between
      academic and non-academic facilities. Patients with higher clinical stage (aOR
      0.58, 95% CI 0.55-0.62) and comorbidities (aOR 0.79, 95% CI 0.71-0.88) were also
      less likely to undergo RPN. CONCLUSIONS: Utilization of RPN has continued to
      increase over time; however, there are significant disparities in its utilization
      according to race and socioeconomic status. Black and Hispanic patients and
      patients in rural communities and with limited insurance were more likely to be
      treated with OPN instead of RPN. PATIENT SUMMARY: The use of robotic surgery in
      partial nephrectomy for management of small renal masses has increased over time.
      We found a significant disparity across different racial and socioeconomic groups
      in use of robotic partial nephrectomy compared to open surgery. Patients living
      in rural areas, with limited insurance, and multiple medical comorbidities were
      more likely to undergo open than robotic partial nephrectomy.

PMID- 29325762
TI  - Assessment of in vivo efficacy of eravacycline against Enterobacteriaceae
      exhibiting various resistance mechanisms: a dose-ranging study and
      pharmacokinetic/pharmacodynamic analysis.
AB  - After the pharmacokinetic (PK) profile of eravacycline, a novel fluorocycline,
      was defined, understanding its pharmacodynamic (PD) profile became essential.
      This study aimed to assess the correlation of the PK/PD index fAUC/MIC (ratio of
      area under the free drug concentration-time curve to MIC) and its magnitude with
      eravacycline's efficacy against Enterobacteriaceae using an immunocompetent
      murine thigh infection model to resemble the immunocompetent environment in
      eravacycline's clinical trials. Eight Enterobacteriaceae isolates with various
      resistance mechanisms were tested. Eravacycline doses ranged from 1-10 mg/kg/day
      and were given either once daily (q24h) or divided into doses every 12 h (q12h)
      over the 24-h treatment period. Antibacterial efficacy was measured as the change
      in log10CFU at 24 h compared with 0 h controls. Composite data were modelled
      using a sigmoid Emax model. Eravacycline MICs ranged from 0.125-0.5 ug/mL. The
      mean fAUC/MIC magnitudes required for stasis and 1-log reduction for the eight
      isolates were 2.9 +/- 3.1 and 5.6 +/- 5.0, respectively. Whilst the humanised
      eravacycline regimen (2.5 mg/kg q12h) pharmacokinetically achieves an fAUC0-24
      that is higher than the fAUC0-24 achieved with the 5 mg/kg q24h dose, the latter
      was associated with greater efficacy, raising a suggestive correlation of the
      peak free drug concentration to MIC (fCmax/MIC) ratio with eravacycline's
      efficacy. This study showed that the magnitudes associated with eravacycline's
      efficacy in an immunocompetent murine thigh model appear to be close to
      achievable targets in human. These data support further development of
      eravacycline for treatment of infections caused by drug-resistant
      Enterobacteriaceae.

PMID- 29325764
TI  - Self-management model in the scheduling of successive appointments in
      rheumatology.
AB  - INTRODUCTION: The rheumatology service of Ciudad Real Hospital, located in an
      autonomous community of that same name that is nearly in the center of Spain,
      implemented a self-management model of successive appointments more than 10 years
      ago. Since then, the physicians of the department schedule follow-up visits for
      their patients depending on the disease, its course and ancillary tests. The
      purpose of this study is to evaluate and compare the self-management model for
      successive appointments in the rheumatology service of Ciudad Real Hospital
      versus the model of external appointment management implemented in 8 of the
      hospital's 15 medical services. MATERIAL AND METHODS: A comparative and
      multivariate analysis was performed to identify variables with statistically
      significant differences, in terms of activity and/or performance indicators and
      quality perceived by users. The comparison involved the self-management model for
      successive appointments employed in the rheumatology service of Ciudad Real
      Hospital and the model for external appointment management used in 8 hospital
      medical services between January 1 and May 31, 2016. RESULTS: In a database with
      more than 100,000 records of appointments involving the set of services included
      in the study, the mean waiting time and the numbers of non-appearances and
      rescheduling of follow-up visits in the rheumatology department were
      significantly lower than in the other services. The number of individuals treated
      in outpatient rheumatology services was 7,768, and a total of 280 patients were
      surveyed (response rate 63.21%). They showed great overall satisfaction, and the
      incidence rate of claims was low. CONCLUSION: Our results show that the self
      management model of scheduling appointments has better results in terms of
      activity indicators and in quality perceived by users, despite the intense
      activity. Thus, this study could be fundamental for decision making in the
      management of health care organizations.

PMID- 29325763
TI  - Clinical experience with three-dimensional printing techniques in orthopedic
      trauma.
AB  - BACKGROUND: To report our experiences with the use of three-dimensional (3D)
      printing in the field of orthopedic trauma. METHODS: This retrospective study
      enrolled 24 patients from three university teaching hospitals in whom 3D printing
      technique was applied: 14 patients with acetabular fractures and 10 patients with
      clavicular shaft fractures. We summarized our experiences with 3D printed bone
      models. RESULTS: Three-dimensional printed acetabular models improved
      understanding of complex acetabular anatomy and fracture pattern to plan the
      optimal positioning of a reduction clamp and the trajectory of screws. Pre
      bending of a reconstruction plate could reduce operative time. We also recorded
      fluoroscopic images of a simulated surgery for percutaneous screw fixation of the
      acetabular posterior column, with the optimal positioning of the guide wire
      determined during the simulation used as a reference during the actual operation.
      This surgical simulation was performed by a resident and served as a helpful
      training method. For fractures of the clavicle, we identified the optimal
      position of anatomical plates using 3D printed clavicle models. CONCLUSION: In
      our experience, 3D printing technique provided surgeons with improved
      understanding of the fracture pattern and anatomy and was effectively used for
      preoperative planning, education of surgical trainees, and performing simulations
      to improve intra-operative technical outcomes.

PMID- 29325766
TI  - Duration of treatment with bisphosphonates at the time of osteonecrosis of the
      jaw onset in patients with rheumatoid arthritis. Review.
AB  - INTRODUCTION: Rheumatoid arthritis (RA) is a frequent and co-morbid condition.
      One of the main complications is induced osteoporosis. Treatments related to this
      complication significantly modify oral and implant management. Affected patients
      represent a population at intermediate risk of osteonecrosis of the jaw (ONJ).
      The objective was to search the literature for durations of treatment with
      bisphosphonates at the time of ONJ occurrence in patients with RA in order to
      obtain an average duration. MATERIALS AND METHODS: A bibliographic search in the
      PubMed/Medline database was carried out using the following equation
      "(osteonecrosis and jaw) and rheumatoid arthritis" with no time limitation. The
      primary study endpoint was the duration of treatment with bisphosphonates (BP) at
      the time of ONJ onset in patients with RA. RESULTS: Twelve articles accounting
      for 50 patients were included. Patients had had a median of 46.8 months of
      treatment with BP before ONJ occurred. Mean, minimum and maximum treatment times
      were 48.68, 6 and 120 months, respectively. The standard deviation was 27.77
      months. DISCUSSION: The median treatment duration in our cohort of patients with
      RA was less than that reported for osteoporosis. We therefore, recommend that
      practitioners take additional precautions regarding oral surgery or implant
      procedures, particularly in patients with RA who have been treated with BP for
      more than 4 years.

PMID- 29325765
TI  - A systematic investigation on the composition, evolution and expression
      characteristics of chemokine superfamily in grass carp Ctenopharyngodon idella.
AB  - Chemokines are a superfamily of small cytokines and characterized based on their
      ability to induce directional migration of cells along a concentration gradient
      by binding to chemokine receptors, which have important roles in immunology and
      development. Due to the numerous and diverse members, systematic identifications
      of chemokine superfamily genes are difficult in many species. To that end, a
      comprehensive analysis of BLAST and scripting language was conducted to
      systematically identify and characterize chemokine system in grass carp
      (Ctenopharyngodon idella). Our results showed that C. idella chemokine
      superfamily consists of 81 chemokines and 37 receptors, in which, most genes
      possess typical structural features of the chemokine superfamily. Phylogenetic
      analyses confirmed the existence of three chemokine subfamilies (CC, CXC and XC)
      in C. idella and revealed their homologous relationships with other species.
      Chemokine receptors are transmembrane receptors and contains CCR, CXCR, XCR and
      ACKR subfamilies. mRNA expression analyses of chemokine superfamily genes
      indicated that many members are sustainably expressed in multiple tissues before
      and after grass carp reovirus (GCRV) or Aeromonas hydrophila infection, which
      provides in vivo evidence for the response patterns after viral or bacterial
      infection. Meanwhile, this study also explored the evolution of chemokine system
      from arthropod to higher vertebrates and then investigated the changes in gene
      number/diversification, gene organization and encoded proteins during vertebrate
      evolution. These results will serve the further functional and evolutional
      studies on chemokine superfamily.

PMID- 29325767
TI  - Primary Synovial Sarcoma arising from gingivo-buccal sulcus harbouring SS18-SSX2
      positive fusion transcript: The 1st reported case in English literature.
AB  - Synovial sarcoma (SS) is a mesenchymal tumour of uncertain histiogenesis that can
      show dual epithelial and mesenchymal differentiation. Thought to arise
      predominantly in deep soft tissue of extremities, these sarcomas have shown that
      they can affect a wide variety of organs and sites, however intraoral mucosal SS
      is rarely encountered and herein the authors present possibly the second reported
      case of a young lady presenting with a slow growing tumour arising in the gingivo
      buccal sulcus that was reported as Synovial sarcoma on biopsy and subsequently
      confirmed using molecular studies, tumour demonstrating SS18-SSX2 fusion
      transcript. Review of the published literature revealed no documented case with
      molecular fusion transcript making this case the first reported case. This case
      also highlights the imperative role of immunohistochemistry in tandem with
      molecular studies to confirm the diagnosis of spindle cell tumours of oral
      cavity, since squamous cell carcinoma, by far remains the commonest malignancy
      arising in mucosa lined oral cavity.

PMID- 29325768
TI  - Retraction notice to Pigment epithelium derived factor play a positive role in
      bone mineralization of osteoblasts derived from diabetic patients [GENE 627C
      (2017) 563 - 568 of retracted article].

PMID- 29325769
TI  - The structural determinants of the bitopic binding mode of a negative allosteric
      modulator of the dopamine D2 receptor.
AB  - SB269652 is a negative allosteric modulator of the dopamine D2 receptor (D2R) yet
      possesses structural similarity to ligands with a competitive mode of
      interaction. In this study, we aimed to understand the ligand-receptor
      interactions that confer its allosteric action. We combined site-directed
      mutagenesis with molecular dynamics simulations using both SB269652 and
      derivatives from our previous structure activity studies. We identify residues
      within the conserved orthosteric binding site (OBS) and a secondary binding
      pocket (SBP) that determine affinity and cooperativity. Our results indicate that
      interaction with the SBP is a requirement for allosteric pharmacology, but that
      both competitive and allosteric derivatives of SB269652 can display sensitivity
      to the mutation of a glutamate residue (E952.65) within the SBP. Our findings
      provide the molecular basis for the differences in affinity between SB269652
      derivatives, and reveal how changes to interactions made by the primary
      pharmacophore of SB269652 in the orthosteric pocket can confer changes in the
      interactions made by the secondary pharmacophore in the SBP. Our insights provide
      a structure-activity framework towards rational optimization of bitopic ligands
      for D2R with tailored competitive versus allosteric properties.

PMID- 29325770
TI  - Development of a non-toxic and non-denaturing formulation process for
      encapsulation of SDF-1alpha into PLGA/PEG-PLGA nanoparticles to achieve sustained
      release.
AB  - Chemokines are known to stimulate directed migration of cancer cells. Therefore,
      the strategy involving gradual chemokine release from polymeric vehicles for
      trapping cancer cells is of interest. In this work, the chemokine stromal cell
      derived factor-1alpha (SDF-1alpha) was encapsulated into nanoparticles composed
      of poly-(lactic-co-glycolic acid) (PLGA) and a polyethylene glycol (PEG)-PLGA co
      polymer to achieve sustained release. SDF-1alpha, and lysozyme as a model
      protein, were firstly precipitated to promote their stability upon encapsulation.
      A novel phase separation method utilising a non-toxic solvent in the form of
      isosorbide dimethyl ether was developed for the individual encapsulation of SDF
      1alpha and lysozyme precipitates. Uniform nanoparticles of 200-250 nm in size
      with spherical morphologies were successfully synthesised under mild formulation
      conditions and conveniently freeze-dried in the presence of hydroxypropyl-beta
      cyclodextrin as a stabiliser. The effect of PLGA carboxylic acid terminal capping
      on protein encapsulation efficiency and release rate was also explored. Following
      optimisation, sustained release of SDF-1alpha was achieved over a period of 72 h.
      Importantly, the novel encapsulation process was found to induce negligible
      protein denaturation. The obtained SDF-1alpha nanocarriers may be subsequently
      incorporated within a hydrogel or other scaffolds to establish a chemokine
      concentration gradient for the trapping of glioblastoma cells.

PMID- 29325771
TI  - A cross-cultural study of acceptability and food pairing for hot sauces.
AB  - This study was conducted to understand the acceptance levels of hot sauces among
      consumers from different culinary cultures. Two newly developed hot sauces
      [fermented red chili pepper with soybean-paste-based sauce(GS) and fermented red
      chili-pepper-based sauce(KS)] were compared with Tabasco sauce(TB) and Sriracha
      sauce(SR). Two separate cross-cultural home-use tests(HUTs) were conducted: pizza
      and cream soup were provided as food items in HUT 1, whereas grilled chicken
      wings and rice noodle soup were provided in HUT 2. Consumers residing in Denmark,
      South Korea, and US participated in each HUT (n?100 per country). Acceptance
      levels and the reasons for (dis)liking particular hot sauces applied to food
      systems were assessed. The food items that paired well with different hot sauces
      when the sauces were applied freely to regular meals were also analyzed among the
      US and Korean subjects. When the hot-sauce samples were applied to pizza and
      cream soup, the preferred order of the samples exhibited a cross-cultural
      agreement (GS = KS > TB). In the case of grilled chicken and rice noodle soup,
      the acceptance rating was similar for the three types of hot sauces among
      Koreans, whereas the acceptance was higher for SR among the US subjects for both
      foodstuffs, while Danish subjects preferred GS and KS over SR. The US subjects
      did not like hot-sauce samples with sweet and weak spiciness, whereas the Korean
      and Danish subjects disliked the hot-sauce sample when it was too spicy and not
      sufficiently sweet. These findings indicate that the matching of particular
      sauces with specific food items is culture-dependent, and this needs to be
      considered when trying to export food products such as hot sauce to other
      countries.

PMID- 29325772
TI  - The association of SNP276G>T at adiponectin gene with insulin resistance and
      circulating adiponectin in response to two different hypocaloric diets.
AB  - BACKGROUND: Several adiponectin gene (ADIPOQ) single nucleotide polymorphisms
      (SNPS) have been related with adiponectin levels and risk for obesity. OBJECTIVE:
      The aim of our study was to analyze the effect of rs1501299 ADIPOQ gene
      polymorphism and dietary intake on total adiponectin levels and insulin
      resistance after two hypocaloric diets in obese subjects. MATERIAL AND METHODS: A
      Caucasian population of 284 obese patients was enrolled in a randomized clinical
      trial with two hypocaloric diets (I: moderate carbohydrates vs II: low fat).
      Before and after 12 weeks on each hypocaloric diet, an anthropometric evaluation,
      an assessment of nutritional intake and a biochemical analysis were realized. The
      statistical analysis was performed for the combined GT and TT as a group (mutant)
      and GG as second group (wild) (dominant model). RESULTS: The genotype
      distribution was 149 GG, 124 GT and 21 TT. With caloric restriction strategies,
      body weight, body mass index (BMI), fat mass, waist circumference, systolic blood
      pressure, total LDL cholesterol, LDL cholesterol and leptin levels decreased.
      Only in subjects with GG genotype, diet I and II decreased fasting insulin
      levels, HOMA-IR and adiponectin levels. The improvement was similar with both
      diets; insulin concentrations (Diet I: -4.7 +/- 1.4 mUI/L vs. Diet II: -5.9 +/-
      1.9 mUI/L: p = .76), HOMA-IR (Diet I: -1.4 +/- 0.6 units vs. Diet II: -2.0 +/-
      0.7 units: p = .56) and adiponectin levels (Diet I: -10.2 +/- 3.4 ng/dl vs. Diet
      II: -14.0 +/- 2.9 ng/dl: p = .33). CONCLUSION: The GG genotype of ADIPOQ gene
      variant (rs1501299) is associated with an increase in adiponectin levels and a
      decrease of insulin and HOMA-IR after weight loss.

PMID- 29325773
TI  - How safe is metformin when initiated in early pregnancy? A retrospective 5-year
      study of pregnant women with gestational diabetes mellitus from India.
AB  - BACKGROUND: The initiation of metformin in early pregnancy in Gestational
      Diabetes mellitus (GDM) remains controversial. The aim of our study was to assess
      the influence of Metformin on maternal and fetal outcomes when initiated within
      the first trimester of pregnancy in GDM. METHODS AND MATERIALS: A retrospective
      analysis of 540 women with diabetes complicating pregnancy (IADPSG criteria) over
      five years (January 2011 to May 2016) was done. The study population comprised of
      patients initiated on (a) metformin within the first trimester (Group A:n = 186),
      (b) metformin after the first trimester (Group B:n = 203) and (c) insulin at any
      time during their pregnancy (Group C:n = 151). The primary outcomes compared were
      prematurity, respiratory distress, birth trauma, 5-min APGAR score, neonatal
      hypoglycaemia and need for phototherapy, while secondary outcomes compared were
      neonatal anthropometric measurements, maternal glycemic control, maternal
      hypertensive complications, postpartum glucose tolerance. RESULTS: Individual and
      composite primary or secondary outcomes in group A were similar to Groups B and
      C, though numerically higher premature births were seen in Group A. There was a
      1.3% overall incidence of stillbirths/IUD, while 1.11% congenital anomalies were
      noted of which 2.15% were in group A and 1.32% were in Group C (p = .16).
      CONCLUSIONS: The initiation of metformin within the first trimester of pregnancy
      has no significant adverse maternal or fetal outcomes. However, vigilance for
      premature births is recommended in women exposed to metformin in early pregnancy.

PMID- 29325774
TI  - Achievement of guideline targets for blood pressure, lipid, and glycaemic control
      in type 2 diabetes: A meta-analysis.
AB  - We assessed global achievement of targets recommended by the American Diabetes
      Association (ADA), European Association for the Study of Diabetes (EASD), and
      National Institute of Health and Care Excellence (NICE) for type 2 diabetes. We
      searched Medline, Embase, and The Cochrane Library for observational studies
      reporting target attainment (2006 to 2017 inclusive) for HbA1c, blood pressure,
      or lipids (low density lipoprotein cholesterol [LDL-C], high density lipoprotein
      cholesterol [HDL-C], or triglycerides). Rates were pooled using a random-effects
      meta-analysis. Study quality and risk of small study of bias was assessed. From
      2491 screened records, 24 studies were included reporting on 369,251 people from
      20 countries. The pooled target achievement rates were; 42.8% (95% CI 38.1-47.5%)
      for glycaemic control, 29.0% (22.9-35.9%) for blood pressure, 49.2% (39.0-59.4%)
      for LDL-C, 58.2% (51.7-64.4%) for HDL-C, and 61.9% (55.2-68.2%) for triglyceride
      control. A higher proportion of people achieved HbA1c targets within Europe and
      North America than the rest of the world. A higher proportion of people achieved
      blood pressure targets in North America than Europe or the rest of the world.
      Meta regression showed no significant improvement in rates by year for any
      target. The achievement of evidence-based targets is markedly suboptimal globally
      and not improving.

PMID- 29325775
TI  - Nutrigenetic variants and cardio-metabolic risk in women with or without
      gestational diabetes.
AB  - AIM: Gestational diabetes mellitus (GDM) is the most frequent metabolic disorder
      in pregnancy and it can be considered a silent risk associated to T2DM and CVD
      later in life. The aim of this study was to investigate the association of
      clinical parameters with nine single nucleotide polymorphisms (SNPs) involved
      with nutrients and metabolism in women with or without GDM in order to identify
      potential routine clinical markers for early prevention. METHODS: Nine gene
      variants associated with nutrients and metabolism, namely PPARG2 rs1801282 (C >
      G); PPARGC1A rs8192678 (C > T); TCF7L2 rs7903146 (C > T); LDLR rs2228671 (C > T);
      MTHFR rs1801133 (C > T); APOA5 rs662799 (T > C); GCKR rs1260326 (C > T); FTO
      rs9939609 (T > A); MC4R rs17782313 (T > C) were genotyped in 104 GDM cases and
      124 controls using High Resolution Melting (HRM) analysis. RESULTS: The genetic
      variant rs7903146 (C > T) in TCF7L2 gene showed a strong association with GDM
      risk (OR: 2.56; 95% CI: [1.24-5.29]). Moreover, a significant correlation was
      observed between lipid parameters and polymorphisms in other genes, namely PPARG2
      [p = 0,03], APOA5 [p = 0,02], MC4R [p = 0,03], LDLR [p = 0,04] and FTO [p =
      0,03]. In addition, rs17782313 variant, mapped close to MC4R gene, was associated
      to BMI in pre-pregnancy [p = 0,02] and at the end of pregnancy [p = 0,03] in GDM
      group. CONCLUSION: In our study, we found significant associations between
      routine clinical parameters and some gene variants connected with nutrients and
      metabolism in women with GDM. These results can provide useful information to
      develop effective tools and possible personalized intervention strategies in a
      timely manner.

PMID- 29325776
TI  - Prevalence of prediabetes and diabetes mellitus among adults residing in
      Cameroon: A systematic review and meta-analysis.
AB  - AIMS: To summarize current data on the prevalence of prediabetes and diabetes
      mellitus in Cameroon. METHODS: Population-based cross-sectional studies published
      between January 1, 2000 and April 30, 2017 including apparently healthy adults
      residing in Cameroon were searched in PubMed, EMBASE, African Journals Online,
      and African Index Medicus. We used a random-effects model to pool data. RESULTS:
      All included studies had a low risk of bias. Six studies were conducted in an
      urban setting only, one in a rural setting only, and five in both settings. The
      overall prevalence of diabetes mellitus was 5.8% (95%CI 4.1-7.9; 12 studies) in a
      pooled sample of 37,147 participants. The prevalence of prediabetes was 7.1%
      (95%CI: 3.0-21.9; 4 studies) in a pooled sample of 5,872 people. In univariable
      meta-regression analysis, the prevalence of diabetes mellitus increased with age,
      hypertension, overweight and obesity. There was no difference for sex and
      settings (rural versus urban). CONCLUSIONS: This study reports a relatively high
      prevalence of diabetes mellitus and prediabetes in Cameroon, with no difference
      between urban and rural settings and between sexes. The main drivers include
      increasing age, overweight and obesity. Community-based educational programs are
      needed to tackle the burden of the disease in the country.

PMID- 29325777
TI  - Data-driven model reference control of MIMO vertical tank systems with model-free
      VRFT and Q-Learning.
AB  - This paper proposes a combined Virtual Reference Feedback Tuning-Q-learning model
      free control approach, which tunes nonlinear static state feedback controllers to
      achieve output model reference tracking in an optimal control framework. The
      novel iterative Batch Fitted Q-learning strategy uses two neural networks to
      represent the value function (critic) and the controller (actor), and it is
      referred to as a mixed Virtual Reference Feedback Tuning-Batch Fitted Q-learning
      approach. Learning convergence of the Q-learning schemes generally depends, among
      other settings, on the efficient exploration of the state-action space.
      Handcrafting test signals for efficient exploration is difficult even for input
      output stable unknown processes. Virtual Reference Feedback Tuning can ensure an
      initial stabilizing controller to be learned from few input-output data and it
      can be next used to collect substantially more input-state data in a controlled
      mode, in a constrained environment, by compensating the process dynamics. This
      data is used to learn significantly superior nonlinear state feedback neural
      networks controllers for model reference tracking, using the proposed Batch
      Fitted Q-learning iterative tuning strategy, motivating the original combination
      of the two techniques. The mixed Virtual Reference Feedback Tuning-Batch Fitted Q
      learning approach is experimentally validated for water level control of a multi
      input-multi output nonlinear constrained coupled two-tank system. Discussions on
      the observed control behavior are offered.

PMID- 29325779
TI  - [Editorial].

PMID- 29325778
TI  - Nonstructural proteins nsp2TF and nsp2N of porcine reproductive and respiratory
      syndrome virus (PRRSV) play important roles in suppressing host innate immune
      responses.
AB  - Recently, we identified a unique -2/-1 ribosomal frameshift mechanism in PRRSV,
      which yields two truncated forms of nonstructural protein (nsp) 2 variants,
      nsp2TF and nsp2N. Here, in vitro expression of individual PRRSV nsp2TF and nsp2N
      demonstrated their ability to suppress cellular innate immune responses in
      transfected cells. Two recombinant viruses were further analyzed, in which either
      nsp2TF was C-terminally truncated (vKO1) or expression of both nsp2TF and nsp2N
      was knocked out (vKO2). Host cellular mRNA profiling showed that a panel of
      cellular immune genes, in particular those involved in innate immunity, was
      upregulated in cells infected with vKO1 and vKO2. Compared to the wild-type
      virus, vKO1 and vKO2 expedited the IFN-alpha response and increased NK cell
      cytotoxicity, and subsequently enhanced T cell immune responses in infected pigs.
      Our data strongly implicate nsp2TF/nsp2N in arteriviral immune evasion and
      demonstrate that nsp2TF/nsp2N-deficient PRRSV is less capable of counteracting
      host innate immune responses.

PMID- 29325780
TI  - Longitudinal atlas for normative human brain development and aging over the
      lifespan using quantitative susceptibility mapping.
AB  - Longitudinal brain atlases play an important role in the study of human brain
      development and cognition. Existing atlases are mainly based on anatomical
      features derived from T1-and T2-weighted MRI. A 4D developmental quantitative
      susceptibility mapping (QSM) atlas may facilitate the estimation of age-related
      iron changes in deep gray matter nuclei and myelin changes in white matter. To
      this end, group-wise co-registered QSM templates were generated over various age
      intervals from age 1-83 years old. Registration was achieved by combining both T1
      weighted and QSM images. Based on the proposed template, we created an accurate
      deep gray matter nuclei parcellation map (DGM map). Notably, we segmented
      thalamus into 5 sub-regions, i.e. the anterior nuclei, the median nuclei, the
      lateral nuclei, the pulvinar and the internal medullary lamina. Furthermore, we
      built a "whole brain QSM parcellation map" by combining existing cortical
      parcellation and white-matter atlases with the proposed DGM map. Based on the
      proposed QSM atlas, the segmentation accuracy of iron-rich nuclei using QSM is
      significantly improved, especially for children and adolescent subjects. The age
      related progression of magnetic susceptibility in each of the deep gray matter
      nuclei, the hippocampus, and the amygdala was estimated. Our automated atlas
      based analysis provided a systematic confirmation of previous findings on
      susceptibility progression with age resulting from manual ROI drawings in deep
      gray matter nuclei. The susceptibility development in the hippocampus and the
      amygdala follow an iron accumulation model; while in the thalamus sub-regions,
      the susceptibility development exhibits a variety of trends. It is envisioned
      that the newly developed 4D QSM atlas will serve as a template for studying brain
      iron deposition and myelination/demyelination in both normal aging and various
      brain diseases.

PMID- 29325781
TI  - Racial inequalities in health: Framing future research.

PMID- 29325782
TI  - Commentary: Easy home gun access and adolescent depression.

PMID- 29325783
TI  - Validation of the AAST EGS acute cholecystitis grade and comparison with the
      Tokyo guidelines.
AB  - BACKGROUND: Acute cholecystitis presents with heterogeneous severity. The Tokyo
      Guidelines 2013 is a validated method to assess cholecystitis severity, but the
      variables are multifactorial. The American Association for the Surgery of Trauma
      (AAST) developed an anatomically based severity grading system for surgical
      diseases, including cholecystitis. Because the Tokyo Guidelines represent the
      gold standard to estimate acute cholecystitis severity, we wished to validate the
      AAST emergency general surgery scoring system and compare the performance of both
      systems for several patient outcomes. METHODS: Adults (>=18 years) with acute
      cholecystitis during 2013-2016 were identified. Baseline demographic
      characteristics, comorbidity severity as defined by Charlson Comorbidity Index
      score, procedure types, and AAST and Tokyo Guidelines 2013 grades were
      abstracted. Outcomes included duration of stay, 30-day mortality, and
      complications. Comparison of the Tokyo Guidelines and AAST grading system was
      performed using receiver operating characteristic (AUROC) curve C statistics.
      RESULTS: There were 443 patients, with a mean (+/-standard deviation) age of 64.8
      (+/-18) years, 59% male. The median (interquartile ratio) Charlson Comorbidity
      score was 3 (0-6). Management included laparoscopic (n = 307, 69.3%), open (n =
      26, 6%), laparoscopy converted to laparotomy (n = 53, 12%), and cholecystostomy
      (n = 57, 12.7%). Comparison of AAST with Tokyo Guidelines AUROC C statistics
      indicated (P < .05) mortality (0.86 vs 0.73), complication (0.76 vs 0.63), and
      cholecystostomy tube utilization (0.80 vs 0.68). CONCLUSION: Emergency general
      surgery grading systems improve disease severity assessment, may improve
      documentation, and guide management. Discrimination of disease severity using the
      AAST grading system outperforms the Tokyo Guidelines for key clinical outcomes.
      The AAST grading system requires prospective validation and further comparison.

PMID- 29325784
TI  - Kinetic analysis of contralateral liver hypertrophy after radioembolization of
      primary and metastatic liver tumors.
AB  - BACKGROUND: Radioembolization induces liver hypertrophy, although the extent and
      rate of hypertrophy are unknown. Our goal was to examine the kinetics of
      contralateral liver hypertrophy after transarterial radioembolization. METHODS: A
      retrospective study (2010-2014) of treatment-naive patients with
      primary/secondary liver malignancies undergoing right lobe radioembolization was
      performed. Computed tomography volumetry was performed before and 1, 3, and 6
      months after radioembolization. Outcomes of interest were left lobe (standardized
      future liver remnant) degree of hypertrophy, kinetic growth rate, and ability to
      reach goal standardized future liver remnant >=40%. Medians were compared with
      the Kruskall-Wallis test. Time to event analysis was used to estimate time to
      reach goal standardized future liver remnant. RESULTS: In the study, 25 patients
      were included. At 1, 3, and 6 months, median degree of hypertrophy was 4%, 8%,
      and 12% (P < .001), degree of hypertrophy relative to baseline future liver
      remnants was 11%, 17%, and 31% (P = .015), and kinetic growth rate was 0.8%,
      0.5%, and 0.4%/week (P = .002). In patients with baseline standardized future
      liver remnant <40% (N= 16), median time to reach standardized future liver
      remnant >=40% was 7.3 months, with 75% accomplishing standardized future liver
      remnant >=40% at 8.2 months. CONCLUSION: Radioembolization induces hypertrophy of
      the contralateral lobe to a similar extent as existing methods, although at a
      lower rate. The role of radioembolization as a dual therapy (neoadjuvant and
      hypetrophy-inducing) for selected patients needs to be studied. (Surgery
      2017;160:XXX-XXX.).

PMID- 29325785
TI  - Characteristics and outcomes of children with ductal-dependent congenital heart
      disease and esophageal atresia/tracheoesophageal fistula: A multi-institutional
      analysis.
AB  - BACKGROUND: Extracardiac birth defects are associated with worse outcomes in
      congenital heart disease (CHD). The impact of esophageal atresia/trachea
      esophageal fistula (EA/TEF) on outcomes after surgery for ductal-dependent CHD is
      unknown. METHODS: Retrospective matched cohort study using the Pediatric Health
      Information System database from 07/2004 to 06/2015. Hospitalizations with ductal
      dependent CHD and EA/TEF, undergoing CHD surgery were included as cases.
      Admissions with ductal-dependent CHD without EA/TEF were matched 3:1 for age at
      admission and Risk Adjustment for Congenital Heart Surgery-1 classification.
      Comparisons were performed using generalized estimating equations. RESULTS: There
      were 124 cases and 372 controls. Cases included 32 (25.8%) low-risk, 86 (69.3%)
      intermediate-risk, and 6 (4.8%) high-risk patients. Cases had more females
      compared to controls (53.2% vs 41.1%, P = .022). Cases were more likely to be
      premature (28.2% vs 13.7%, P = .001) and low birth weight (29.8% vs 11.8%, P <
      .001). Cases had a similar frequency of Down syndrome, and
      DiGeorge/Velocardiofacial syndrome, but a higher frequency of anorectal
      malformations (4.3% vs 2.4%, P < .001) and renal anomalies (27.4% vs 9.9%, P <
      .001) than controls. Cases had a higher mortality on univariate (22.0% vs 8.4%, P
      < .001) and multivariable analysis (odds ratio 2.45, 95%, confidence interval
      1.34 - 4.49). Prematurity also was significantly associated with mortality on
      multivariable analysis. Cases had a longer duration of mechanical ventilation,
      longer hospital duration of stay, and higher total cost than controls (all P <
      .001). CONCLUSION: In children with ductal-dependent CHD, EA/TEF is associated
      with increased morbidity, mortality and resource utilization. A majority of
      patients undergo EA/TEF repair prior to congenital heart disease surgery.
      (Surgery 2017;160:XXX-XXX.).

PMID- 29325787
TI  - Discussion.

PMID- 29325786
TI  - A proactive outreach intervention that decreases readmission after hepatectomy.
AB  - BACKGROUND: After hepatectomy, 7%-19% of patients are readmitted within 30 days,
      accounting for substantial cost and poor patient experience. The purpose of this
      study was to analyze the impact of a proactive outreach intervention on
      readmissions. METHODS: Consecutive patients undergoing hepatectomy by a single
      surgeon 2012-2016 were identified in a prospectively maintained database. In
      August 2013 a postoperative intervention was implemented; an advanced practice
      provider called each patient within 72 hours of discharge. Readmission rates were
      compared pre- and postintervention using standard statistics. RESULTS: Two
      hundred thirty-one patients met the inclusion criteria and major hepatectomy was
      performed in 45.5% of patients. Although the complication rate was similar (25.0%
      preintervention and 19.4% postintervention, P = .324), readmissions within 30
      days of operation decreased from 14.5% pre- to 6.5% postintervention (P = .046).
      Approximately 30% of outreach interactions required outpatient intervention.
      Factors associated with readmission on univariate analysis included increased
      operative time (P = .007), major hepatectomy (P = .012), hemi or extended
      hepatectomy (P = .032), second stage operation (P = .031), bile leak (P = 0.022),
      and any complication/modified Accordion complication >= 3 within 30 days (P
      <.0001). On multivariate analysis, lack of post-discharge intervention (P = .012)
      and bile leak (P = .031) were independently associated with readmission.
      CONCLUSION: These data demonstrate the efficacy of a proactive communication
      intervention after discharge to decrease readmissions after hepatectomy. The
      additional work created by the intervention is likely offset by decreased
      inpatient care needs and costs. Identification of high-risk populations and
      application of technology are likely to lead to further improvements.

PMID- 29325788
TI  - Impact of the gastrojejunal anatomic position as the mechanism of delayed gastric
      emptying after pancreatoduodenectomy.
AB  - BACKGROUND: This study investigated the impact of gastrojejunal anatomic position
      on the incidence of delayed gastric emptying after pancreatoduodenectomy.
      METHODS: A total of 160 patients were included in the retrospective analysis. The
      relative anatomic position of the gastrojejunostomy was evaluated using coronal
      and sagittal plane computed tomography images on postoperative day 7; the coronal
      cardia anastomotic angle and the sagittal fundus anastomotic angle were measured.
      In the validation study, 64 consecutive patients were enrolled, and gastric
      emptying was evaluated using water-soluble contrast medium. The extent of gastric
      emptying was graded as grade I (no gastric dilatation and no stasis), grade II
      (gastric dilatation but no stasis), or grade III (gastric dilatation and stasis).
      RESULTS: Patients with grades B (n = 8) and C (n = 22) delayed gastric emptying
      were included in the delayed gastric emptying group (n = 30), and the others were
      included in the nondelayed gastric emptying group (n = 130). The coronal cardia
      anastomotic angle was not significantly different between the 2 groups, whereas
      the sagittal fundus anastomotic angle was significantly greater in the delayed
      gastric emptying group compared to the nondelayed gastric emptying group (median
      50.3 vs 64.5 degrees, P < .001). Multivariate analysis, including various risk
      factors of delayed gastric emptying, indicated that a sagittal fundus anastomotic
      angle >60 degrees was the only independent risk factor of delayed gastric
      emptying (odds ratio, 16.59). In the validation study, the median degree of
      sagittal fundus anastomotic angle increased as the gastric emptying grade
      increased (grade I, 44.3 degrees; grade II, 55.3 degrees; grade III, 60.7
      degrees; P = .014 by analysis of variance). CONCLUSION: The gastrojejunal
      anatomic position after pancreatoduodenectomy has a significant impact on the
      incidence of delayed gastric emptying. (Surgery 2017;160:XXX-XXX.).

PMID- 29325789
TI  - Long-term outcomes following ileal pouch-anal anastomosis in patients with
      indeterminate colitis.
AB  - BACKGROUND: The advisability of performing ileal pouch-anal anastomosis for
      patients with indeterminate colitis is debated. Indeterminate colitis is found in
      up to 15% of inflammatory bowel disease colectomy specimens. We determined long
      term outcomes in patients diagnosed with indeterminate colitis undergoing ileal
      pouch-anal anastomosis. METHODS: Fifty-six patients were included with a mean
      follow-up of 14 +/- 7 years. Long-term behavior was defined based on surgeon
      assessment as "Crohn disease-like" in patients who subsequently developed clear
      signs of Crohn disease and as "non-Crohn disease-like." Long-term function was
      assessed using the Cleveland Global Quality of Life and Pouch Functional Score.
      RESULTS: Thirty-nine percent of patients developed Crohn disease-like behavior,
      and 61% developed non-Crohn disease-like behavior. Both groups experienced a high
      rate of pouchitis (57%). Crohn disease-like patients required more anti
      inflammatory/immunomodulatory medications (95% vs 18%, P < .001), dilatations for
      afferent-limb strictures (41% vs 0%, P < .001), and pouch reoperations (32% vs
      6%, P = .02). Eight patients required pouch excision or diversion (7 with Crohn
      disease-like behavior). The Pouch Functional Score was equivalent between groups.
      CONCLUSION: Long-term function after ileal pouch-anal anastomosis for the
      majority of indeterminate colitis patients was good. Approximately 40% eventually
      exhibited Crohn disease-like behavior, but the majority had acceptable function
      and quality of life. Ileal pouch-anal anastomosis is an appropriate surgical
      option for indeterminate colitis patients after informed consent.

PMID- 29325790
TI  - How do oral and maxillofacial surgeons manage concussion?
AB  - Craniofacial trauma results in distracting injuries that are easy to see, and as
      oral and maxillofacial surgeons (OMFS) we gravitate towards injuries that can be
      seen and are treatable surgically. However, we do tend not to involve ourselves
      (and may potentially overlook) injuries that are not obvious either visually or
      radiographically, and concussion is one such. We reviewed the records of 500
      consecutive patients who presented with facial fractures at the Queen Elizabeth
      Hospital, Birmingham, to identify whether patients had been screened for
      concussion, and how they had been managed. Of the 500 cases 186 (37%) had
      concussion, and 174 (35%) had a more severe traumatic brain injury. The
      maxillofacial team documented loss of consciousness in 314 (63%) and pupillary
      reactions in 215 (43%). Ninety-three (19%) were referred for a neurosurgical
      opinion, although most of these were patients who presented with a Glasgow coma
      scale (GCS) of <=13. Only 37 patients (7%) were referred to the traumatic brain
      injury clinic. Recent reports have indicated that 15% of all patients diagnosed
      with concussion have symptoms that persist for longer than two weeks. These can
      have far-reaching effects on recovery, and have an appreciable effect on the
      psychosocial aspects of the patients' lives. As we have found, over one third of
      patients with craniofacial trauma are concussed. We think, therefore, that all
      patients who have been referred to OMFS with craniofacial trauma should be
      screened for concussion on admission, and at the OMFS follow up clinic. In
      addition, there should be an agreement between consultants that such patients
      should be referred to the traumatic brain injury clinic for follow up.

PMID- 29325791
TI  - The therapeutic effects of Cannabis and cannabinoids: An update from the National
      Academies of Sciences, Engineering and Medicine report.
AB  - The National Academies of Sciences, Engineering and Medicine conducted a rapid
      turn-around comprehensive review of recent medical literature on The Health
      Effects of Cannabis and Cannabinoids. The 16-member committee adopted the key
      features of a systematic review process, conducting an extensive search of
      relevant databases and considered 10,000 recent abstracts to determine their
      relevance. Primacy was given to recently published systematic reviews and primary
      research that studied one of the committee's 11 prioritized health endpoints-
      therapeutic effects; cancer incidence; cardiometabolic risk; respiratory disease;
      immune function; injury and death; prenatal, perinatal and postnatal outcomes;
      psychosocial outcomes; mental health; problem Cannabis use; and Cannabis use and
      abuse of other substances. The committee developed standard language to
      categorize the weight of evidence regarding whether Cannabis or cannabinoids use
      for therapeutic purposes are an effective or ineffective treatment for the
      prioritized health endpoints of interest. In the Therapeutics chapter reviewed
      here, the report concluded that there was conclusive or substantial evidence that
      Cannabis or cannabinoids are effective for the treatment of pain in adults;
      chemotherapy-induced nausea and vomiting and spasticity associated with multiple
      sclerosis. Moderate evidence was found for secondary sleep disturbances. The
      evidence supporting improvement in appetite, Tourette syndrome, anxiety,
      posttraumatic stress disorder, cancer, irritable bowel syndrome, epilepsy and a
      variety of neurodegenerative disorders was described as limited, insufficient or
      absent. A chapter of the NASEM report enumerated multiple barriers to conducting
      research on Cannabis in the US that may explain the paucity of positive
      therapeutic benefits in the published literature to date.

PMID- 29325792
TI  - Chronic obstructive pulmonary disease and community acquired pneumonia:
      Additional studies are required.

PMID- 29325793
TI  - Mucocutaneous hyperpigmentation.

PMID- 29325794
TI  - Association of Posture and Ambulation With Function 30 Days After Hospital
      Discharge in Older Adults with Heart Failure.
AB  - PURPOSE: The aim of this work was to investigate the predictive value of in
      hospital posture and ambulatory activity for 30 days following discharge on
      functional status in older patients with heart failure. METHODS AND RESULTS: We
      undertook a prospective observational pilot study of 27 patients (78 +/- 9.8 y,
      51.8% female) admitted with heart failure. Participants wore 2 inclinometric
      accelerometers to record posture in-hospital and an ankle accelerometer to record
      ambulatory activity in-hospital and 30 days after discharge. Function was
      assessed on the day after discharge (Timed Up and Go [TUG], Short Physical
      Performance Battery [SPPB], hand grip strength) and 30 days after discharge.
      Length of stay was 5.1 +/- 3.9 days. Participants spent 63.0 +/- 19.2% of their
      hospital time lying down, 30.2 +/- 18.7% sitting, 5.3 +/- 4.2% standing, and 1.9
      +/- 8.6% ambulating. Thirty-day mean post-discharge stepping was 4890 +/- 2285
      steps/day. Each 10% increase in hospital lying time was associated with 0.7 s
      longer TUG time (95% confidence interval [CI] 0.2-1.9) at 30 days. Each 1000
      additional daily steps in the post-discharge period was associated with a 0.8
      point higher SPPB score (95% CI 0.1-1.0) at 30 days. Handgrip strength was
      unchanged. CONCLUSIONS: Older patients with heart failure were sedentary during
      hospitalization, which may contribute to decreased functional performance.
      Physical activity after discharge may minimize this negative effect.

PMID- 29325795
TI  - Insertional Mutagenesis Confounds the Mechanism of the Morbid Phenotype of a
      PLNR9C Transgenic Mouse Line.
AB  - BACKGROUND: A mouse line with heterozygous transgenic expression of phospholamban
      carrying a substitution of cysteine for arginine 9 (TgPLNR9C) under the control
      of alpha-myosin heavy chain (alphaMHC) promoter features dilated cardiomyopathy,
      heart failure, and premature death. METHODS AND RESULTS: Determination of
      transgene chromosomal localization by conventional methods shows that in this
      line the transgenic array of 13 PLNR9C expression cassettes, arranged in a head
      to-tail tandem orientation, have integrated into the bidirectional promoter of
      the alphaMHC (Myh6) gene and the gene for the regulatory noncoding RNA Myheart
      (Mhrt), both of which are known to be involved in cardiac development and
      pathology. Expression of the noncoding RNA Mhrt in TgPLNR9C mice exhibits
      profound deregulation, despite the presence of the second, intact allele.
      CONCLUSIONS: The TgPLNR9C mouse strain is, in the best case, a functionally
      ambiguous phenocopy of the human PLNR9C heterozygote, because a similar
      constellation of genetically programmed events can not occur in a patient.
      Publications featuring "cardiac-specific overexpression" are focused on the
      phenotype and typically forgo the definition of the transgene integration site or
      transgene temporal expression profile, so caution should be exercised in
      attributing clinical relevance to pathologic phenomena observed in alphaMHC
      driven transgenes.

PMID- 29325796
TI  - LCZ696 (Sacubitril/Valsartan), an Angiotensin-Receptor Neprilysin Inhibitor,
      Attenuates Cardiac Hypertrophy, Fibrosis, and Vasculopathy in a Rat Model of
      Chronic Kidney Disease.
AB  - BACKGROUND: Chronic kidney disease (CKD) is associated with cardiac hypertrophy,
      fibrosis, and increased risk of cardiovascular mortality. LCZ696
      (sacubitril/valsartan) is a promising agent that has shown significant potential
      in treatment of heart failure. We hypothesized that LCZ696 is more effective than
      valsartan alone in the treatment of cardiovascular abnormalities associated with
      experimental CKD. METHODS AND RESULTS: Male Sprague-Dawley rats underwent 5/6
      nephrectomy and were subsequently randomized to no treatment (CKD), 30 mg/kg
      valsartan (VAL), or 60 mg/kg LCZ696 (LCZ). After 8 weeks, cardiovascular
      parameters, including markers of inflammation, oxidative stress, mitochondrial
      abundance/function, hypertrophy, and fibrosis, were measured. Treatment with LCZ
      resulted in significant improvements in the heart-body weight ratio and serum
      concentrations of N-terminal pro-B-type natriuretic peptide and fibroblast growth
      factor 23 along with improvement of kidney function. In addition, LCZ ameliorated
      aortic fibrosis and cardiac hypertrophy and fibrosis, reduced markers of cardiac
      oxidative stress and inflammation, and improved indicators of mitochondrial
      mass/function. Although VAL also improved some of these indices, treatment with
      LCZ was more effective than VAL alone. CONCLUSIONS: CKD-associated cardiovascular
      abnormalities, including myocardial hypertrophy, fibrosis, inflammation,
      oxidative stress, and mitochondrial depletion/dysfunction, were more effectively
      attenuated by LCZ treatment than by VAL alone.

PMID- 29325797
TI  - Consequences of Retained Defibrillator and Pacemaker Leads After Heart
      Transplantation-An Underrecognized Problem.
AB  - BACKGROUND: Cardiovascular implantable electronic devices (CIEDs) are common in
      patients undergoing heart transplantation (HT), and complete removal is not
      always possible at the time of transplantation. METHODS: We retrospectively
      assessed the frequency of retained CIED leads and clinical consequences in
      consecutive HT patients from 2013 to 2016. Clinical outcomes included bacteremia,
      upper-extremity deep venous thrombosis (UEDVT), lead migration, and inability to
      perform magnetic resonance imaging (MRI). RESULTS: A total of 138 patients (55 +/
      11 years of age, 76% male) were identified; 37 (27%) had retained lead fragments
      (RLFs) at discharge. Patients with RLFs were older, had longer lead implantation
      time before HT, and a higher prevalence of dual-coil CIED leads compared with
      those without RLFs (P < .05 for all). Lead implantation time was identified as an
      independent predictor for RLFs (P < .05). Patients with RLFs had a higher
      frequency of DVT compared with the non-RLF group during the 1-year study period
      (42% vs 21%; P < .04). There was no difference in bacteremia. Fourteen patients
      (38%) could not undergo clinically indicated MRI. CONCLUSION: RLFs after HT occur
      commonly and are associated with a higher rate of UEDVT and limit the use of MRI.
      Although no significant difference was found in the rates of bacteremia between
      the groups, this finding might be explained by the overall low incidence.
      Patients with risk factors for RLFs should be identified before transplantation,
      and complete lead removal should be considered with a multidisciplinary approach.

PMID- 29325798
TI  - Evaluation of the performance of two tuberculosis interferon gamma release assays
      (IGRA-ELISA and T-SPOT.TB) for diagnosing Mycobacterium tuberculosis infection.
AB  - OBJECTIVES: The IGRA-ELISA and T-SPOT.TB are widely used in China. The aim of the
      study was to evaluate the performance of the two assays in diagnosis
      Mycobacterium tuberculosis infection. METHODS: Of the 3727 patients in the study,
      204 underwent testing using both the T-SPOT.TB and IGRA-ELISA, 1794 were tested
      using the T-SPOT.TB only, and 1729 were tested using the IGRA-ELISA only. The
      positive rate and consistency of the two assays were analyzed, and their
      sensitivity and specificity for diagnosing active tuberculosis were compared.
      RESULTS: There were no significant differences in the positive rate between the T
      SPOT.TB test (25.8%) and IGRA-ELISA (28.6%), p = .065. The two assays were highly
      consistent, with a kappa value of 0.852 (p < .0001) and a total coincidence rate
      of 92.7%. For the diagnosis of active tuberculosis, the sensitivity and
      specificity values of the T-SPOT.TB test were 82.9% (107/129) and 78.6%
      (1309/1665), respectively, and those of IGRA-ELISA were 81.7% (94/115) and 75.2%
      (1214/1614), respectively. There were no significant differences in sensitivity
      (p > .05), but the specificity of the T-SPOT.TB test was slightly higher than
      that of IGRA-ELISA (p = .023). CONCLUSION: Both in terms of diagnosing M.
      tuberculosis infection and ruling out active tuberculosis, the performance of the
      IGRA-ELISA-a simple, almost labor-free assay that allows simultaneous processing
      of a very large number of samples-was well-matched with that of T-SPOT.TB test.
      However, IGRAs cannot be used as the only test to diagnose active tuberculosis.

PMID- 29325799
TI  - Elevated circulating homocysteine and high-sensitivity C-reactive protein jointly
      predicts post-stroke depression among Chinese patients with acute ischemic
      stroke.
AB  - BACKGROUND: Homocysteine (HCY) and high sensitivity C reactive protein (hs-CRP)
      were suggested to be involved in post-stroke depression (PSD), which is a
      frequent mood disorder after stroke. However, the combined effect of HCY and hs
      CRP on PSD remains unclear. METHODS: A total of 598 acute ischemic stroke
      patients from 7 of 26 centers participating in the China Antihypertensive Trial
      in Acute Ischemic Stroke with HCY or hs-CRP measurements were included in this
      analysis. PSD status was evaluated by 24-item Hamilton Depression Rating Scale at
      3 months after stroke. RESULTS: Two hundred and forty-one (40.30%) participants
      were considered as PSD. HCY and hs-CRP levels were not significantly different
      between PSD and non-PSD patients. Interesting, in a maximally adjusted model, the
      odds ratio (95% confidence interval) of PSD was 1.90 (1.18-3.06) for coexistence
      of HCY >= 14.65 MUmol/l and hs-CRP >= 1.90 mg/l compared with the other levels
      (HCY < 14.65 MUmol/l and/or hs-CRP < 1.90 mg/l). Adding combination of HCY and hs
      CRP to a model containing conventional risk factors could significantly improve
      risk reclassification for PSD. CONCLUSIONS: Coexistence of both higher HCY and
      higher hs-CRP in the acute phase of ischemic stroke were associated with
      subsequent PSD, independently of established conventional risk factors.

PMID- 29325800
TI  - Platelet to lymphocyte ratio is a predictive marker of prognosis and therapeutic
      effect of postoperative chemotherapy in non-metastatic esophageal squamous cell
      carcinoma.
AB  - Increasing evidence has indicated that inflammatory biomarkers, including the
      neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and
      prognostic nutritional index (PNI), can be used as prognostic indicators in
      esophageal squamous cell carcinoma (ESCC). However, the best predictor for
      prognosis in ESCC remains controversial. Few studies have focused on the
      association between inflammatory biomarkers and postoperative chemotherapy. A
      cohort of 515 non-metastatic ESCC patients was retrospectively reviewed.
      Harrell's concordance index (c-index) was used to identify the optimal cut-off
      values of the inflammatory markers, and their prognostic value was compared. Cox
      multivariate analysis indicated that, among these inflammatory biomarkers, PLR
      (>=133 vs. <133) was the only independent prognostic factor for poor OS [hazard
      ratio = 1.370, 95% confidence intervals = 1.076-1.745, p = .011]. The c-index
      values of PLR were higher compared with NLR and PNI. For patients with PLR < 133,
      the surgery plus chemotherapy group had significantly longer OS than the surgery
      group alone (p = .004), but the significant difference of OS between these two
      groups was not observed in patients with PLR >= 133 (p = .624). PLR is a
      predictive marker of prognosis and therapeutic effect of postoperative
      chemotherapy in non-metastatic ESCC.

PMID- 29325801
TI  - Editorial: The role of medical physics in lung SBRT.
AB  - Stereotactic body radiation therapy (SBRT) has become a standard treatment for
      non-operable patients with early stage non-small cell lung cancer (NSCLC). In
      this context, medical physics community has largely helped in the starting and
      the growth of this technique. In fact, SBRT requires the convergence of many
      different features for delivering large doses in few fractions to small moving
      target in an heterogeneous medium. The special issue of last month, was focused
      on the different physics challenges in lung SBRT. Eleven reviews were presented,
      covering: imaging for treatment planning and for treatment assessment; dosimetry
      and planning optimization; treatment delivery possibilities; image guidance
      during delivery; radiobiology. The current cutting edge role of medical physics
      was reported. We aimed to give a complete overview of different aspects of lung
      SBRT that would be of interest to both physicists implementing this technique in
      their institutions and more experienced physicists that would be inspired to
      start research projects in areas that still need further developments. We also
      feel that the role that medical physicists have played in the development and
      safe implementation of SBRT, particularly in lung region, can be taken as an
      excellent example to be translated to other areas, not only in Radiation Oncology
      but also in other health sectors.

PMID- 29325802
TI  - Utilization of large volume zwitterionic hydrophilic interaction liquid
      chromatography for the analysis of polar pharmaceuticals in aqueous environmental
      samples: Benefits and limitations.
AB  - Benefits and limitations of HILIC were studied for the analysis of extreme polar
      organic contaminants in aqueous environmental matrices. A sensitive analytical
      method was developed and validated for the detection of 11 pharmaceuticals, 15
      pharmaceutical metabolites and transformation products and the artificial
      sweetener acesulfame in aqueous environmental samples. The analytical method
      consisted of a simple and non-specific sample preparation based on freeze-drying
      followed by detection with large injection volume (70 MUL) zwitterionic HILIC-ESI
      MS/MS. Robustness studies showed a high sensitivity of the retention times and
      peak shapes to variations of the acetonitrile/water ratio of both the eluent and
      the diluent. Thus, a thorough sample and eluent preparation is required to obtain
      reproducible results. Extreme matrix effects of >200% were observed for
      emtricitabine and acyclovir, which could be traced to the co-elution of nitrate
      and chloride, respectively. These matrix effects and those of other analytes
      could be efficiently compensated by using deuterated, 13C and 15N-labeled
      internal standards. The developed method was able to detect the selected 27
      analytes in treated wastewater, surface water and groundwater down to limit of
      quantification (LOQ) in the lower ng/L range. Appreciable concentrations were
      detected, ranging up to 110 MUg/L (guanyl urea) in treated wastewater, up to 5.1
      MUg/L (oxipurinol) in surface water and up to 6.1 MUg/L (acesulfame) in
      groundwater. In a German drinking water, only the X-ray contrast medium
      diatrizoate and the artificial sweetener acesulfame were quantified above LOQ
      with 0.19 MUg/L and 0.35 MUg/L, respectively.

PMID- 29325803
TI  - Coronary artery disease in athletes: An adverse effect of intense exercise?
AB  - Regular physical exercise is responsible for various health benefits, and is
      recommended for primary and secondary cardiovascular (CV) prevention. Despite
      these recognized benefits, various clinical events can occur in athletes,
      including acute myocardial infarction and sudden cardiac death (SCD); the main
      cause of SCD in veteran athletes is coronary artery disease (CAD). The
      relationship between intense exercise training and CAD is controversial, and a U
      shaped association has been hypothesized. If this is the case, screening for
      subclinical CAD in older athletes may be justified, and various different
      methodologies have been proposed. However, the methodology for screening veteran
      athletes is not consensual, and several markers of CAD, in addition to clinical
      CV risk factors, could improve risk stratification in this population. In the
      present paper we review the published data on CAD in athletes, focusing on the
      relationship between the dose of exercise and CAD, as well as the implications
      for pre-participation screening of veteran athletes.

PMID- 29325804
TI  - Heart failure in numbers: Estimates for the 21st century in Portugal.
AB  - INTRODUCTION AND OBJECTIVE: Heart failure is a major public health problem that
      affects a large number of individuals and is associated with high mortality and
      morbidity. This study aims to estimate the probable scenario for HF prevalence
      and its consequences in the short-, medium- and long-term in Portugal. METHODS:
      This assessment is based on the EPICA (Epidemiology of Heart Failure and
      Learning) project, which was designed to estimate the prevalence of chronic heart
      failure in mainland Portugal in 1998. Estimates of heart failure prevalence were
      performed for individuals aged over 25 years, distributed by age group and
      gender, based on data from the 2011 Census by Statistics Portugal. RESULTS: The
      expected demographic changes, particularly the marked aging of the population,
      mean that a large number of Portuguese will likely be affected by this syndrome.
      Assuming that current clinical practices are maintained, the prevalence of heart
      failure in mainland Portugal will increase by 30% by 2035 and by 33% by 2060,
      compared to 2011, resulting in 479 921 and 494 191 affected individuals,
      respectively. CONCLUSIONS: In addition to the large number of heart failure
      patients expected, it is estimated that the hospitalizations and mortality
      associated with this syndrome will significantly increase its economic impact.
      Therefore, it is extremely important to raise awareness of this syndrome, as this
      will favor diagnosis and early referral of patients, facilitating better
      management of heart failure and helping to decrease the burden it imposes on
      Portugal.

PMID- 29325805
TI  - Reduced plaque size and inflammation in the APP23 mouse model for Alzheimer's
      disease after chronic application of polymeric nanoparticles for CNS targeted
      zinc delivery.
AB  - A local dyshomeostasis of zinc ions in the vicinity of amyloid aggregates has
      been proposed in Alzheimer's disease (AD) due to the sequestration of zinc in
      senile plaques. While an increase in zinc levels may promote the aggregation of
      amyloid beta (Abeta), increased brain zinc might also be beneficial rescuing some
      pathological alterations caused by local zinc deficiency. For example, increased
      Abeta degradation by metalloproteinases, and a reduction in inflammation can be
      hypothesized. In addition, zinc may allow a stabilization of the number of
      synapses in AD brains. Thus, to evaluate whether altering zinc-levels within the
      brain is a promising new target for the prevention and treatment of AD, we
      employed novel zinc loaded nanoparticles able to deliver zinc into the brain
      across the blood-brain barrier. We performed in vivo studies using wild type (WT)
      and APP23 mice to assess plaque load, inflammatory status and synapse loss.
      Furthermore, we performed behavioral analyses. After chronically injecting these
      nanoparticles for 14 days, our results show a significant reduction in plaque
      size and effects on the pro-inflammatory cytokines IL-6 and IL-18. On behavioral
      level we could not detect negative effects of increased brain zinc levels in
      APP23 mice and treatment with g7-NP-Zn normalized the observed hyperlocomotion of
      APP23 mice. Therefore, we conclude that a targeted increase in brain zinc levels
      may have beneficial effects in AD.

PMID- 29325806
TI  - RIFM fragrance ingredient safety assessment, pentanedioic acid, 1,5-dimethyl
      ester, CAS Registry Number 1119-40-0.

PMID- 29325807
TI  - RIFM fragrance ingredient safety assessment, dodecanenitrile, CAS Registry Number
      2437-25-4.

PMID- 29325808
TI  - Dutch breast reconstruction guideline.
AB  - Treatment of breast cancer is complex and multidisciplinary by nature, with
      protocols that are updated continuously. During preoperative multidisciplinary
      team meetings, regularly there is discussion between team members regarding
      optimal timing and type of breast reconstruction, due to conflicting interests of
      oncological and reconstructive treatments. Therefore, a multidisciplinary,
      evidence-based guideline for breast reconstruction in women undergoing breast
      conserving therapy or mastectomy for breast cancer, or following prophylactic
      mastectomy was developed by a multidisciplinary working group. The guideline was
      drafted in accordance with the AGREE II instrument, designed to assess the
      quality of guidelines with broad international support. For the recommendations,
      scientific evidence was considered together with other key aspects, such as
      working group member expertise, patient preferences, costs, availability of
      facilities and/or organizational aspects. Recommendations provide an answer to
      the primary questions, and are based on the best scientific evidence available
      together with the most important considerations by the working group. In
      accordance with the GRADE method, the level of scientific evidence and the
      importance given to considerations by the working group jointly determined the
      strength of the recommendation. The guideline aims to provide practical guidance
      for plastic surgeons and other members of the multidisciplinary breast cancer
      team. The implementation of the present breast reconstruction guideline may
      contribute to optimizing the delivery of care and support for breast
      reconstruction patients, it may stimulate evidence-based plastic surgery, it may
      reduce undesirable variation in clinical practice between health care providers,
      and improve the overall quality of life of breast reconstruction patients.

PMID- 29325809
TI  - Spanish validation of the Exercise Therapy Burden Questionnaire (ETBQ) for the
      assessment of barriers associated to doing physical therapy for the treatment of
      chronic illness.
AB  - BACKGROUND AND OBJETIVE: To validate the Spanish version of the Exercise Therapy
      Burden Questionnaire (ETBQ) for the assessment of barriers associated to doing
      physical therapy for the treatment of chronic ailments. PATIENTES AND METHODS: A
      sample of 177 patients, 55.93% men and 44.07% women, with an average age of
      51.03+/-14.91 was recruited. The reliability of the questionnaire was tested with
      Cronbach's alpha coefficient, and the validity of the instrument was assessed
      through the divergent validation process and factor analysis. RESULTS: The factor
      analysis was different to the original questionnaire, composed of a dimension, in
      this case determined three dimensions: (1) General limitations for doing physical
      exercise. (2) Physical limitations for doing physical exercise. (3) Limitations
      caused by the patients' predisposition to their exercises. The reliability of the
      test-retest was measured through the intraclass correlation coefficient (ICC) and
      the Bland-Altman plot. Cronbach's alpha was 0.8715 for the total ETBQ. The ICC of
      the test-retest was 0.745 and the Bland-Altman plot showed no systematic trend.
      CONCLUSION: We have obtained the translated version in Spanish of the ETBQ
      questionnaire.

PMID- 29325810
TI  - Current and Future Initiatives for Radiation Oncology at the National Cancer
      Institute in the Era of Precision Medicine.

PMID- 29325811
TI  - Personalized Medicine Versus Quality: Contradictory or Mutually Dependent?

PMID- 29325812
TI  - Transcatheter mitral valve replacement in mitral annulus calcification - "The art
      of computer simulation".
AB  - There is considerable interest in transcatheter prosthetic valve treatment for
      mitral valve disease in high-risk individuals. Although the presence of mitral
      annular calcium (MAC) may provide an anchoring zone for such devices, results to
      date have been modest with reported technical failure rates approaching 30% in
      specialist centers. This in part relates to the risk of left ventricular outflow
      tract obstruction and device dislodgment but also to the lack of specific imaging
      guidelines to plan for such procedures. We present the use of finite element
      analysis and computer simulation based on cardiac CT in three patients with
      severe MAC in whom transcatheter devices were considered. In the first two cases,
      the computer simulations were performed after the clinical procedure and were
      concordant with the clinical outcome. For the third case, computer simulation was
      performed prior to the clinical procedure. This indicated unsuitability for
      transcatheter device deployment and a subsequent medical management was adopted.
      Overall, our initial results suggest that computer simulation may have the
      potential to improve patient selection for transcatheter mitral valve replacement
      in the presence of significant MAC.

PMID- 29325813
TI  - Cardiac function and exercise adaptation in 8 children with LPIN1 mutations.
AB  - INTRODUCTION: Lipin-1 deficiency is a major cause of rhabdomyolysis that are
      precipitated by febrile illness. The prognosis is poor, with one-third of
      patients dying from cardiac arrest during a crisis episode. Apart from acute
      rhabdomyolysis, most patients are healthy, showing normal clinical and cardiac
      ultrasound parameters. PATIENTS AND METHODS: We report cardiac and exercise
      examinations of 8 children carrying two LPIN1 mutations. The examinations were
      performed outside of a myolysis episode, but one patient presented with fever
      during one examination. RESULTS: All but one patient displayed normal resting
      cardiac function, as determined by echocardiography. One patient exhibited slight
      left ventricular dysfunction at rest and a lack of increased stroke volume during
      cycle ramp exercise. During exercise, peripheral muscle adaptation was impaired
      in 2 patients compared to healthy controls: they presented an abnormal increase
      in cardiac output relative to oxygen uptake: dQ/dVO2=8.2 and 9.5 (>2DS of
      controls population). One patient underwent 2 exercise tests; during one test,
      the patient was febrile, leading to acute rhabdomyolysis in the following hours.
      He exhibited changes in recovery muscle reoxygenation parameters and an increased
      dQ/dVO2 during exercise compared with that under normothermia (7.9 vs 6), which
      did not lead to acute rhabdomyolysis. The four patients assessed by cardiac 1H
      magnetic resonance spectroscopy exhibited signs of intracardiac steatosis.
      CONCLUSION: We observed abnormal haemodynamic profiles during exercise in 3/8
      patients with lipin-1 deficiency, suggesting impaired muscle oxidative
      phosphorylation during exercise. Fever appeared to be an aggravating factor. One
      patient exhibited moderate cardiac dysfunction, which was possibly related to
      intracardiac stored lipid toxicity.

PMID- 29325814
TI  - Corrigendum to "Development of hypomelanotic macules is associated with
      constitutive activated mTORC1 in tuberous sclerosis complex" [Mol. Genet. Metab.
      120(4) (Apr 2017) 384-391].

PMID- 29325815
TI  - Intersectionality and the LGBT Cancer Patient.
AB  - OBJECTIVES: To present the ways in which race, ethnicity, class, gender, and
      sexual orientation interact in the context of cancer risk, access to care, and
      treatment by health care providers. Cancer risk factors, access to care, and
      treatment for lesbian, gay, bisexual, and transgender (LGBT) patients are
      discussed within the context of intersectionality and cultural humility. DATA
      SOURCES: Peer reviewed articles, cancer organizations, and clinical practice.
      CONCLUSION: LGBT patients have multiple identities that intersect to create
      unique experiences. These experiences shape their interactions with the health
      care system with the potential for positive or negative consequences. More data
      is needed to describe the outcomes of those experiences and inform clinical
      practice. IMPLICATIONS FOR NURSING PRACTICE: Oncology nurses have an obligation
      to acknowledge patients' multiple identities and use the practice of cultural
      humility to provide individualized, patient-centered care.

PMID- 29325816
TI  - LGBT Cultural Competence and Interventions to Help Oncology Nurses and Other
      Health Care Providers.
AB  - OBJECTIVES: To define and give an overview of the importance of lesbian, gay,
      bisexual, and transgender (LGBT) cultural competency and offer some initial steps
      on how to improve the quality of care provided by oncology nurses and other
      health care professionals. DATA SOURCES: A review of the existing literature on
      cultural competency. CONCLUSION: LGBT patients experience cancer and several
      other diseases at higher rates than the rest of the population. The reasons for
      these health care disparities are complex and include minority stress, fear of
      discrimination, lower rates of insurance, and lack of access to quality,
      culturally competent care. Addressing the health care disparities experienced by
      LGBT individuals and families requires attention to the actual needs, language,
      and support networks used by patients in these communities. Training on how to
      provide quality care in a welcoming and non-judgmental way is available and can
      improve health equity. IMPLICATIONS FOR NURSING PRACTICE: Health care
      professionals and institutions that acquire cultural competency training can
      improve the overall health of LGBT patients who currently experience significant
      health care disparities.

PMID- 29325817
TI  - Cancer Screening Considerations and Cancer Screening Uptake for Lesbian, Gay,
      Bisexual, and Transgender Persons.
AB  - OBJECTIVES: To describe the current state of cancer screening and uptake for
      lesbian, gay, bisexual, and transgender (LGBT) persons and to propose cancer
      screening considerations for LGBT persons. DATA SOURCES: Current and historic
      published literature on cancer screening and LGBT cancer screening; published
      national guidelines. CONCLUSION: Despite known cancer risks for members of the
      LGBT community, cancer screening rates are often low, and there are gaps in
      screening recommendations for LGBT persons. We propose evidence-based cancer
      screening considerations derived from the current literature and extant cancer
      screening recommendations. IMPLICATIONS FOR NURSING PRACTICE: The oncology nurse
      plays a key role in supporting patient preventive care and screening uptake
      through assessment, counseling, education, advocacy, and intervention. As
      oncology nurses become expert in the culturally competent care of LGBT persons,
      they can contribute to the improvement of quality of care and overall well-being
      of this health care disparity population.

PMID- 29325818
TI  - Simultaneous determination of voriconazole, posaconazole, itraconazole and
      hydroxy-itraconazole in human plasma using LCMS/MS.
AB  - INTRODUCTION: Invasive fungal infections are an increasing cause of mortality and
      morbidity in high risk patient populations such as those on immunosuppressive
      therapy. Triazole antifungals are recommended for the prevention and treatment of
      such infections. The aim of this study was to develop and validate a simple,
      sensitive and robust LCMS/MS method for the simultaneous analysis in human plasma
      of three frequently used antifungal drugs: voriconazole, posaconazole, and
      itraconazole. METHODS: Precipitation reagent, containing deuterated internal
      standards, is added to 50MUL of plasma. The vials are vortexed before
      centrifugation. The organic supernatant is transferred to a polypropylene vial
      and 1MUL is injected into the Waters Acquity(r) Ultra Performance Liquid
      Chromatography system coupled with a Waters Acquity(r) TQ Detector system.
      Chromatographic separation is achieved on a BEH C18 column using gradient elution
      with mobile phases consisting of 2mM ammonium acetate with 0.1% formic acid in
      water and methanol. Run time is <5min between injections. RESULTS: The evaluation
      of the LCMS/MS triazole method showed good precision (intra-assay CVs<6.7%, inter
      assay CVs<8.3%). The lower limit of quantitation for all antifungal triazoles
      tested was 0.10mg/L. Passing Bablok comparisons of voriconazole (n=50) and
      posaconazole (n=50) showed good correlation with the current HPLC method
      (Voriconazole LCMS=0.94(HPLC)+0.03, r2=0.99; Posaconazole LCMS=1.18(HPLC)-0.04,
      r2=0.95). Passing Bablok comparisons of itraconazole and hydroxy-itraconazole
      (n=18) showed good agreement with an external referral laboratory's antifungal
      LCMS/MS method (Itraconazole LCMS=1.00(referral lab)+0.01, r2=0.99; Hydroxy
      Itraconazole LCMS=1.05(referral lab)+0.04, r2=0.99). External quality assurance
      samples for posaconazole and voriconazole (n=12, UK NEQAS Antifungal Pilot Panel)
      were assayed 'blind' and results were in good agreement with consensus mean
      values (both r2=0.99). CONCLUSION: The rapid pre-analytical sample preparation
      procedure, short chromatographic time, limit of quantitation and linear range
      make this LCMS/MS method suitable for determination of plasma voriconazole,
      posaconazole, itraconazole and hydroxy-itraconazole levels in a high throughput
      laboratory.

PMID- 29325820
TI  - An assessment of shedding with the oral rabies virus vaccine strain SPBN GASGAS
      in target and non-target species.
AB  - A safety requirement for live vaccines is investigating possible shedding in
      recipients since the presence of replication competent vaccine in secretions
      could result in direct and indirect horizontal transmission. This is especially
      relevant for oral rabies vaccine baits that are deliberately distributed into the
      environment. In the current study, survival of an oral rabies virus vaccine, SPBN
      GASGAS, was examined in excretions from different target and non-target species;
      red fox, raccoon dog, small Indian mongoose, raccoon, striped skunk, domestic
      dog, domestic cat and domestic pig. Saliva - and (pooled) fecal samples collected
      at different time points after oral administration of the vaccine strain were
      examined for the presence of viral RNA (rt-PCR). All PCR-positive and a subset of
      PCR-negative samples were subsequently investigated for the presence of
      infectious virus by isolation in cell culture (RTCIT). Up to 7 days post vaccine
      administration viral RNA could be detected in 50 of 758 fecal samples but no
      infectious virus was detected in any of the examined PCR-positive fecal samples.
      In contrast, RNA-fragments were detected in 248 of 1053 saliva swabs for an
      extended period (up to 10 days) after vaccine administration, but viable virus
      was only present during the first hours post vaccine administration in 38
      samples. No infectious vaccine virus was isolated in saliva swabs taken 24 h or
      more after vaccine administration. Hence, no active shedding of the vaccine virus
      SPBN GASGAS after oral administration occurred and the virus isolated during the
      initial hours was material originally administered and not a result of virus
      replication within the host. Thus, potential horizontal transmission of this
      vaccine virus is limited to a short period directly after vaccine bait uptake. It
      can be concluded that the environmental risks associated with shedding after
      distributing vaccine baits containing SPBN GASGAS are negligible.

PMID- 29325819
TI  - Explanations for the high potency of HPV prophylactic vaccines.
AB  - HPV L1 virus-like particle (VLP) vaccines administered in a prime/boost series of
      three injections over six months have demonstrated remarkable prophylactic
      efficacy in clinical trials and effectiveness in national immunization programs
      with high rates of coverage. There is mounting evidence that the vaccines have
      similar efficacy and effectiveness even when administered in a single dose. The
      unexpected potency of one dose of these VLP vaccines may largely be attributed to
      structural features of the particles, which lead to the efficient generation of
      long-lived antigen-specific antibody-producing cells and unique features of the
      virus life cycle that make the HPV virions highly susceptible to antibody
      mediated inhibition of infection.

PMID- 29325821
TI  - DNA vaccine encoding myristoylated membrane protein (MMP) of rock bream
      iridovirus (RBIV) induces protective immunity in rock bream (Oplegnathus
      fasciatus).
AB  - Rock bream iridovirus (RBIV) causes severe mass mortalities in rock bream
      (Oplegnathus fasciatus) in Korea. In this study, we investigated the potential of
      viral membrane protein to induce antiviral status protecting rock bream against
      RBIV infection. We found that fish administered with ORF008L (myristoylated
      membrane protein, MMP) vaccine exhibited significantly higher levels of survival
      compared to ORF007L (major capsid protein, MCP). Moreover, ORF008L-based DNA
      vaccinated fish showed significant protection at 4 and 8 weeks post vaccination
      (wpv) than non-vaccinated fish after infected with RBIV (6.7 * 105) at 23 
      degrees C, with relative percent survival (RPS) of 73.36% and 46.72%,
      respectively. All of the survivors from the first RBIV infection were strongly
      protected (100% RPS) from re-infected with RBIV (1.1 * 107) at 100 dpi. In
      addition, the MMP (ORF008L)-based DNA vaccine significantly induced the gene
      expression of TLR3 (14.2-fold), MyD88 (11.6-fold), Mx (84.7-fold), ISG15 (8.7
      fold), PKR (25.6-fold), MHC class I (13.3-fold), Fas (6.7-fold), Fas ligand (6.7
      fold), caspase9 (17.0-fold) and caspase3 (15.3-fold) at 7 days post vaccination
      in the muscle (vaccine injection site). Our results showed the induction of
      immune responses and suggest the possibility of developing preventive measures
      against RBIV using myristoylated membrane protein-based DNA vaccine.

PMID- 29325822
TI  - Parental vaccine hesitancy in Italy - Results from a national survey.
AB  - In Italy, in 2016, we conducted a cross-sectional survey to estimate vaccine
      hesitancy and investigate its determinants among parents of children aged 16-36
      months. Data on parental attitudes and beliefs about vaccinations were collected
      through a questionnaire administered online or self-administered at
      pediatricians' offices and nurseries. Parents were classified as pro-vaccine,
      vaccine-hesitant or anti-vaccine, according to self-reported tetanus and measles
      vaccination status of their child. Multivariable logistic regression was used to
      investigate factors associated with hesitancy. A total of 3130 questionnaires
      were analysed: 83.7% of parents were pro-vaccine, 15.6% vaccine-hesitant and 0.7%
      anti-vaccine. Safety concerns are the main reported reason for refusing (38.1%)
      or interrupting (42.4%) vaccination. Anti-vaccine and hesitant parents are
      significantly more afraid than pro-vaccine parents of short-term (85.7 and 79.7%
      vs 60.4%) and long-term (95.2 and 72.3% vs 43.7%) vaccine adverse reactions. Most
      pro-vaccine and hesitant parents agree about the benefits of vaccinations. Family
      pediatricians are considered a reliable source of information by most pro-vaccine
      and hesitant parents (96.9 and 83.3% respectively), against 45% of anti-vaccine
      parents. The main factors associated with hesitancy were found to be: not having
      received from a paediatrician a recommendation to fully vaccinate their child
      [adjusted odds ratio (AOR): 3.21, 95% CI: 2.14-4.79], having received discordant
      opinions on vaccinations (AOR: 1.64, 95% CI: 1.11-2.43), having met parents of
      children who experienced serious adverse reactions (AOR: 1.49, 95% CI: 1.03
      2.15), and mainly using non-traditional medical treatments (AOR: 2.05, 95% CI:
      1.31-3.19). Vaccine safety is perceived as a concern by all parents, although
      more so by hesitant and anti-vaccine parents. Similarly to pro-vaccine parents,
      hesitant parents consider vaccination an important prevention tool and trust
      their family pediatricians, suggesting that they could benefit from appropriate
      communication interventions. Training health professionals and providing
      homogenous information about vaccinations, in line with national recommendations,
      are crucial for responding to their concerns.

PMID- 29325823
TI  - Photo(geno)toxicity changes associated with hydroxylation of the aromatic
      chromophores during diclofenac metabolism.
AB  - Diclofenac (DCF) can cause adverse reactions such as gastrointestinal, renal and
      cardiovascular disorders; therefore, topical administration may be an attractive
      alternative to the management of local pain in order to avoid these side effects.
      However, previous studies have shown that DCF, in combination with sunlight,
      displays capability to induce photosensitivity disorders. In humans, DCF is
      biotransformed into hydroxylated metabolites at positions 4' and 5 (4'OH-DCF and
      5OH-DCF), and this chemical change produces non negligible alterations of the
      drug chromophore, resulting in a significant modification of its light-absorbing
      properties. In the present work, 5OH-DCF exhibited higher photo(geno)toxic
      potential than the parent drug, as shown by several in vitro assays (3T3 NRU
      phototoxicity, DNA ssb gel electrophoresis and COMET), whereas 4'OH-DCF did not
      display significant photo(geno)toxicity. This could be associated, at least
      partially with their more efficient UV-light absorption by 5OH-DCF metabolite and
      with a higher photoreactivity. Interestingly, most of the cellular DNA damage
      photosensitized by DCF and 5OH-DCF was repaired by the cells after several hours,
      although this effect was not complete in the case of 5OH-DCF.

PMID- 29325824
TI  - In utero combined di-(2-ethylhexyl) phthalate and diethyl phthalate exposure
      cumulatively impairs rat fetal Leydig cell development.
AB  - Phthalate diesters, including di-(2-ethylhexyl) phthalate (DEHP) and diethyl
      phthalate (DEP), are chemicals to which humans are ubiquitously exposed. Humans
      are exposed simultaneously to multiple environmental chemicals, including DEHP
      and DEP. There is little information available about how each chemical may
      interact to each other if they were exposed at same time. The present study
      investigated effects of the combinational exposure of rats to DEP and DEHP on
      fetal Leydig cell development. The results showed that the gestational (GD12-20)
      exposure of DEP + DEHP resulted in synergistic and/or dose-additive effects on
      the development of fetal Leydig cell. The lowest observed adverse-effect levels
      (LOAEL) for fetal Leydig cell (aggregation and cell size), and StAR expressions
      were of 10 mg/kg and, lower than when these chemicals were exposed alone. Also,
      mathematical modeling the response curves supports the dose-addition model over
      integrated-addition model. Overall, these data demonstrate that individual
      phthalate with a similar mechanism of action can elicit cumulative, dose
      additive, and sometimes synergistic, effects on the development of male
      reproductive system when administered as a mixture.

PMID- 29325825
TI  - [Thromboembolic disease in pediatric oncology].
AB  - The survival rate of children with cancer is now close to 80 %, as a result of
      continuous improvement in diagnostic and treatment procedures. Prevention and
      treatment of treatment-associated complications is now a major challenge.
      Thromboembolic venous disease, due to multifactorial pathogenesis, is a frequent
      complication (up to 40 % asymptomatic thrombosis in children with cancer),
      responsible for significant morbidity. Predominantly in children with acute
      lymphoblastic leukemia, lymphoma, or sarcoma, thromboembolic disease justifies
      primary prophylaxis in certain populations at risk, whether genetic or
      environmental. The curative treatment, well codified, is based on the
      administration of low-molecular-weight heparin. In the absence of robust
      pediatric prospective studies, this article proposes a concise decision tree
      summarizing the preventive and curative strategy.

PMID- 29325826
TI  - Myoclonic absence seizures with complex gestural automatisms.
AB  - Epilepsy with myoclonic absences is a rare generalized epilepsy syndrome with
      distinctive seizures. Two unrelated children had mild developmental impairment
      and onset of myoclonic-absences at 3 and 8 years. Seizures were characterized by
      bilateral 3 Hz myoclonic jerks superimposed on tonic abduction of the upper
      limbs. Events lasted 10-60 s, and complex gestural automatisms were often
      observed; in one case, a boy undid his seatbelt and attempted to exit a moving
      vehicle. Post-ictally, both children immediately regained awareness without
      recollection of their actions. Ictal EEGs showed 3 Hz generalized spike-wave.
      Complex automatisms have not been described in myoclonic absence seizures. This
      generalized seizure type can be confused with focal seizures when these ictal
      behaviours occur.

PMID- 29325827
TI  - Efficient oligo nucleotide mediated CRISPR-Cas9 gene editing in Aspergilli.
AB  - CRISPR-Cas9 technologies are revolutionizing fungal gene editing. Here we show
      that survival of specific Cas9/sgRNA mediated DNA double strand breaks (DSBs)
      depends on the non-homologous end-joining, NHEJ, DNA repair pathway and we use
      this observation to develop a tool, TAPE, to assess protospacer efficiency in
      Aspergillus nidulans. Moreover, we show that in NHEJ deficient strains, highly
      efficient marker-free gene targeting can be performed. Indeed, we show that even
      single-stranded oligo nucleotides efficiently work as repair templates of
      specific Cas9/sgRNA induced DNA DSBs in A. nidulans, A. niger, and in A. oryzae
      indicating that this type of repair may be wide-spread in filamentous fungi.
      Importantly, we demonstrate that by using single-stranded oligo nucleotides for
      CRISPR-Cas9 mediated gene editing it is possible to introduce specific point
      mutations as well gene deletions at efficiencies approaching 100%. The efficiency
      of the system invites for multiplexing and we have designed a vector system with
      the capacity of delivering Cas9 and multiple sgRNAs based on polymerase III
      promoters and tRNA spacers. We show that it is possible to introduce two point
      mutations and one gene insertion in one transformation experiment with a very
      high efficiency. Our system is compatible with future high-throughput gene
      editing experiments.

PMID- 29325828
TI  - Misleading conclusions on the effects of sleeve gastrectomy on body composition
      due to statistical errors.

PMID- 29325829
TI  - Allogeneic Stem Cell Transplantation for Advanced Myelodysplastic Syndrome:
      Comparison of Outcomes between CD34+ Selected and Unmodified Hematopoietic Stem
      Cell Transplantation.
AB  - In this study, we compared transplantation outcomes of allogeneic hematopoietic
      stem cell transplantation (HSCT) in patients with advanced myelodysplastic
      syndrome (MDS) who received a CD34+ cell-selected and those who received an
      unmodified allograft. This analysis initially included 181 patients, 60 who
      received a CD34+ cell-selected transplant and 121 who received an unmodified
      transplant. Owing to significant differences in disease characteristics, the
      analysis was limited to patients with <10% blasts before HSCT (n = 145). Two
      groups were defined: low risk, with low- and intermediate-risk cytogenetics
      (CD34+, n = 39; unmodified, n = 46), and high risk: poor and very poor risk
      cytogenetics (CD34+, n = 19; unmodified, n = 41). In the low-risk group, the
      incidence of grade II-IV acute graft-versus-host disease (aGVHD) at 1 year post
      transplantation was 18% in the CD34+ subgroup versus 41.3% in the unmodified
      subgroup (P = .015). There were no differences between the subgroups in the
      incidence of grade III-IV aGVHD. The incidence of chronic graft-versus-host
      disease (cGVHD) at 3 years in the 2 subgroups was 5.3% and 56%, respectively (P <
      .001). At 3 years post-transplantation, relapse, overall survival (OS), and
      relapse-free survival (RFS) were similar in the CD34+ and unmodified subgroups:
      8.1% versus 19.4% (P = .187), 58.5% versus 53.7% (P = .51), and 59.5% versus
      52.4% (P = .448). However, the composite outcome combining extensive cGVHD-free
      status and relapse-free status (CRFS) at 3 years was 59.5% in the CD34+ group
      versus 19.2% in the unmodified group (P < .001). In the high-risk group, grade II
      IV aGVHD at 1 year was 31.6% in the CD34+ subgroup versus 24.4% in the unmodified
      subgroup (P = .752). There were no differences between the subgroups in the
      incidence of grade III-IV aGVHD. The incidence of cGVHD at 3 years in the 2
      subgroups was 0% versus 27.6% (P = .013). At 3 years post-transplantation,
      relapse, OS, RFS, and CRFS in the 2 subgroups were 31.6% versus 69.3% (P = .007),
      35.5% versus 14.5% (P = .068), 31.6% versus 10.7% (P = .045), and 31.6% versus
      6.1% (P = .001), respectively. Cytogenetic abnormalities at diagnosis and
      transplant type had significant univariate associations with RFS in the high-risk
      cohort. Only cytogenetics (P = .03) remained associated with this outcome in a
      multivariate model. OS was similar in the 2 transplant groups; however, CRFS was
      superior in the CD34+ cell-selected transplant group.

PMID- 29325831
TI  - Sexual Dysfunction Among Young Men: Overview of Dietary Components Associated
      With Erectile Dysfunction.
AB  - BACKGROUND: Sexual dysfunction is relatively common in young men, presenting in
      diverse manifestations, including erectile dysfunction (ED), for which dietary
      modifications, including increased intake of dietary antioxidants, have been
      suggested as promising and cost-efficient approaches. AIM: To assess the
      consumption of selected dietary antioxidants, in particular flavonoids, in
      relation to ED symptoms in young men. METHODS: Men 18 to 40 years old were
      invited to complete an anonymous web-based questionnaire for this case-control
      study. ED was diagnosed with the International Index of Erectile Function (IIEF)
      and flavonoid intake was recorded using food-frequency questionnaires, with an
      emphasis on flavonoid-rich foods such as coffee, fruits, etc. Participants
      without ED (IIEF score >= 26; n = 264) formed the control group and those with ED
      (IIEF score < 26; n = 86) formed the case group. OUTCOMES: Dietary flavonoid
      intake. RESULTS: Men with ED reported a lower median monthly intake of total
      flavonoids (-2.18 g, 95% CI = -3.15 to -1.21, P < .001) and all flavonoid
      subclasses (P < .001) compared with controls. Adjustment of intake for age and
      body mass index showed that consumption of flavonoids 50 mg/day lowered the risk
      for ED by 32% (odds ratio = 0.68, 95% CI = 0.55-0.85, P < .001). Of all recorded
      flavonoids, flavones appeared to contribute the most to healthy erectile
      function. Controls reported a greater consumption of vegetables and fruits, a
      lower intake of dairy and alcoholic beverages, and a less intense smoking habit
      compared with cases (P < .001). CLINICAL IMPLICATIONS: Increased intake of
      fruits, vegetables, and flavonoids decreases the risk of ED in young men.
      STRENGTH AND LIMITATIONS: The strength of this study stems from the innovative
      hypothesis, the young age of participants, and the suggested therapeutic effects
      of cheap dietary components against ED. Limitations include the relatively small
      sample and cross-sectional design. CONCLUSION: Low flavonoid-in particular
      flavone-intake is associated with ED in young adult men. Mykoniatis I,
      Grammatikopoulou MG, Bouras E, et al. Sexual Dysfunction Among Young Men:
      Overview of Dietary Components Associated With Erectile Dysfunction. J Sex Med
      2018;15:176-182.

PMID- 29325830
TI  - Blood and Marrow Transplant Clinical Trials Network Report on the Development of
      Novel Endpoints and Selection of Promising Approaches for Graft-versus-Host
      Disease Prevention Trials.
AB  - Graft-versus-host disease (GVHD) is a common complication after hematopoietic
      cell transplantation (HCT) and associated with significant morbidity and
      mortality. Preventing GVHD without chronic therapy or increasing relapse is a
      desired goal. Here we report a benchmark analysis to evaluate the performance of
      6 GVHD prevention strategies tested at single institutions compared with a large
      multicenter outcomes database as a control. Each intervention was compared with
      the control for the incidence of acute and chronic GVHD and overall survival and
      against novel composite endpoints: acute and chronic GVHD, relapse-free survival
      (GRFS), and chronic GVHD, relapse-free survival (CRFS). Modeling GRFS and CRFS
      using the benchmark analysis further informed the design of 2 clinical trials
      testing GVHD prophylaxis interventions. This study demonstrates the potential
      benefit of using an outcomes database to select promising interventions for
      multicenter clinical trials and proposes novel composite endpoints for use in
      GVHD prevention trials.

PMID- 29325832
TI  - The PICS Technique: A Novel Approach for Residual Curvature Correction During
      Penile Prosthesis Implantation in Patients With Severe Peyronie's Disease Using
      the Collagen Fleece TachoSil.
AB  - BACKGROUND: Correction of residual curvature during inflatable penile prosthesis
      (IPP) implantation in patients with Peyronie's disease (PD) by plaque incision
      and grafting is a common approach. AIM: To present a novel technique for residual
      curvature correction during IPP implantation using collagen fleece (TachoSil,
      Baxter Healthcare Corp, Deerfield, IL, USA). METHODS: After the IPP (Titan Touch,
      Coloplast, Minneapolis, MN, USA) is placed, the implant is inflated maximally.
      When residual curvature exceeds 40 degrees , the PICS (penile implant in
      combination with the Sealing technique) technique is performed. The device is
      deflated, and a circumcising skin incision and penile degloving are performed.
      After elevation of the neurovascular bundle, the device is reinflated maximally.
      Plaque incision is performed at the point of maximum curvature using
      electrocautery. This leads to penile straightening because the tension is
      removed. In the next step, the defect of the tunica is closed with collagen
      fleece, which sticks to the tunica and defect without any sutures needed. The
      neurovascular bundle is reapproximated and the Buck fascia is closed. This is
      followed by closure of penile skin. OUTCOMES: Primary outcome measurements were
      straightening rates, operative times, 5-item International Index of Erectile
      Function (IIEF-5) scores at follow-up, immediate and late complications, and
      patient satisfaction. RESULTS: The PICS technique was applied to 15 patients.
      Mean patient age was 61.7 years (52-79 years). Mean residual curvature after IPP
      was 66.7 degrees  (50-90 degrees ). Mean operative time was 117.3 minutes (100
      140 minutes). Mean follow-up was 15.1 months (1-29 months). 12 of 15 patients
      (80%) showed a totally straight penis. 3 patients (20%) had residual curvature of
      10 degrees  at follow-up, which did not interfere with sexual intercourse. Mean
      IIEF-5 score at follow-up was 24.2 (22-25). No immediate or late complications
      occurred. All patients were satisfied with the surgical outcomes. CLINICAL
      IMPLICATIONS: This novel technique prevents puncture or injury of the device,
      because the collagen fleece does not require suture fixation into the defect
      after plaque incision. STRENGTHS AND LIMITATIONS: This technique can be applied
      to patients with severe PD who display residual curvature greater than 40 degrees
      after IPP placement. It is a fast approach with low complication rates.
      Limitations include the small patient population and short follow-up. CONCLUSION:
      The PICS technique represents a safe and time-saving approach for residual
      curvature correction during IPP placement in patients with PD and prevents device
      puncture. Hatzichristodoulou G. The PICS Technique: A Novel Approach for Residual
      Curvature Correction During Penile Prosthesis Implantation in Patients With
      Severe Peyronie's Disease Using the Collagen Fleece TachoSil. J Sex Med
      2018;15:416-421.

PMID- 29325833
TI  - Treatment of Graves' disease in children: The Portuguese experience.
AB  - INTRODUCTION: Graves' disease (GD) is an autoimmune thyroid disease, common in
      adults but rare in children. The best therapeutic approach remains controversial.
      OBJECTIVES: To ascertain the current treatment of pediatric GD in Portugal and to
      assess the clinical and biochemical factors that determine definitive/long-term
      remission after treatment with antithyroid drugs (ATDs). PATIENTS AND METHODS: A
      retrospective analysis of data about pediatric GD treatment collected from a
      nationwide survey conducted by the Portuguese Society of Pediatric Endocrinology
      and Diabetology from May to August 2013. Population was categorized based on sex,
      age, use of ATDs, dosage, treatment duration, adverse reactions, thyrotropin
      receptor-stimulating antibody (TRAB) titer, remission and remission/relapse
      rates, and definitive treatment, and divided into group A (with ongoing
      treatment) and group B (with treatment stopped). Group B was subdivided into
      'Remission', 'Remission+relapse' and 'No remission' subgroups based on the course
      of disease. The same parameters were compared between both groups. RESULTS:
      Survey response rate was 77%; 152 subjects, 116 female, mean age at diagnosis
      11.23+/-3.46 years. They all started treatment with ATDs, 70.4% with thiamazole,
      with a mean treatment duration of 32.38+/-28.29 months, and 5.9% had adverse
      effects. Remission rate was 32.6%. Lower age at diagnosis correlated with higher
      remission rates. Treatment duration was longer when propylthiouracil was used.
      Initial TRAB titer was significantly higher in the 'No remission' group. Surgery
      and radioiodine were used as second-line treatments. CONCLUSION: Our study
      results were similar to those reported in the literature. Age and TRAB titer were
      identified as potential clinical and laboratory determinants of remission. Based
      on risk/benefit analysis, it was concluded that treatment should be
      individualized based on age, accessibility to treatments, and physician's
      experience.

PMID- 29325834
TI  - A computed-tomography-scan-based template to place the femoral component in
      accurate rotation with respect to the surgical epicondylar axis in total knee
      arthroplasty.
AB  - BACKGROUND: Femoral rotational alignment is considered an essential factor for
      total knee arthroplasty because malrotation of femoral components results in poor
      outcomes. To obtain proper alignment, we developed a superimposable computed
      tomography (CT) scan-based template to intraoperatively determine the accurate
      surgical epicondylar axis (SEA), and evaluated the effectiveness of this CT
      template. METHODS: In the experimental group (n=55), three serial slices of CT
      images, including medial and lateral epicondyles, were merged into a single
      image, and SEA was overlaid. SEA was traced onto an image of an assumed distal
      femoral resection level; this combined image was then printed out onto a
      transparent film as a CT template. Following a distal femoral resection in TKA,
      SEA was duplicated onto the femoral surface. Thereafter, the posterior condyle
      was resected parallel to this SEA. In the control group (n=53), posterior
      condyles were resected at three degrees of the external rotation from the
      posterior condylar line (PCL). A posterior condylar angle (PCA) between PCL of
      the femoral component and SEA was postoperatively evaluated. Positive values
      indicated external rotation of the femoral component from the SEA. RESULTS: In
      the experimental group, PCA was 0.01 degrees +/-1.61 degrees , and three cases
      were considered as outliers (greater than three degrees or less than -3 degrees).
      Conversely, in the control group, PCA was 0.10 degrees +/-2.4 degrees , and 12
      cases were considered as outliers. Consequently, dispersion of PCA data was
      significantly smaller in the experimental group (P=0.004). CONCLUSIONS: The CT
      template accurately determined intraoperative SEA.

PMID- 29325835
TI  - Synthetic mesh vs. allograft extensor mechanism reconstruction in total knee
      arthroplasty - A systematic review of the literature and meta-analysis.
AB  - BACKGROUND: Extensor mechanism disruption after total knee arthroplasty (TKA) is
      a devastating complication. Reconstruction with allograft and synthetic mesh has
      been described. However, these reports have typically been small case series, and
      controversy exists with regard to which reconstruction technique is optimal.
      METHODS: The authors performed a systematic review using PUBMED, MEDLINE, EMBASE,
      BIOSIS, Clinicaltrials.gov, and Cochrane Database of Systematic Reviews
      identifying 14 articles meeting inclusion criteria and producing 204 knees for
      comparison. Studies with repairs performed under full knee extension were
      included. Case reports and non-English studies were excluded. Available
      demographics and clinical outcome data were collected from each study.
      Appropriate statistical analysis was performed to compare the variables. RESULTS:
      Baseline demographics and patient complexity were similar between the two
      cohorts. Reconstruction success rates (76% allograft vs. 74% mesh), average time
      to diagnosis/treatment, Knee Society Scores (KSS), knee range of motion/extensor
      lag, and complication rates yielded no statistical difference. Synthetic mesh was
      used more frequently with concomitant revision of components. DISCUSSION: This
      systematic review shows equivalent success of allograft and synthetic mesh with
      approximately 25% failure rate in both groups. Periprosthetic joint infection
      remains a common and significant complication and reason for failure in both
      groups. Overall, synthetic mesh showed equivalent extensor mechanism
      reconstruction success as allograft but with much lower cost, near universal
      availability, lack of disease transmission, and potential for diminishing graft
      stretch-out. Future research in larger case series or comparative study is needed
      to help aid in management of this largely unsolved problem in total knee
      reconstruction.

PMID- 29325836
TI  - Interleukin-6 and leptin levels are associated with preoperative pain severity in
      patients with osteoarthritis but not with acute pain after total knee
      arthroplasty.
AB  - BACKGROUND: Identifying drivers of pain that can serve as novel drug targets is
      important for improving perioperative analgesia. Total knee arthroplasty (TKA) is
      associated with significant postoperative pain. Cytokines contribute to the
      pathophysiology of osteoarthritis (OA) and associated pain. However, the
      influence of perioperative cytokine levels after TKA surgery upon postoperative
      pain remains unexplored. METHODS: We designed a prospective observational study
      to profile three proinflammatory cytokines, interleukin-6 (IL-6), tumor necrosis
      factor alpha (TNFalpha), and leptin in serum, synovial, and cerebrospinal fluid
      of TKA patients perioperatively to determine associations between cytokine levels
      and pain. We characterized time-trajectories in cytokines pre- and post-surgery
      and explored their relationships to pain across gender. RESULTS: Preoperative
      pain, measured by functional pain disability scores (PDQ), was predictive of
      postoperative pain. There were no gender differences in severity of preoperative
      pain or acute postoperative pain. Serum IL-6, serum leptin, and synovial fluid
      leptin were positively correlated with body mass index and preoperative pain
      severity. Stratification of patients by gender revealed strong correlations
      between serum IL-6, leptin, and PDQ only in females, suggesting that females may
      be more sensitive to the nociceptive actions of these cytokines. Although serum
      IL-6 increased dramatically (and TNFalpha increased modestly) four hours after
      surgery and remained elevated at 72h; they were not associated with the severity
      of acute postoperative pain. CONCLUSIONS: Our data suggest that while
      preoperative chronic pain is predictive of the severity of acute postoperative
      pain in TKA patients, the pre- and post-operative inflammatory status does not
      predict postoperative pain.

PMID- 29325837
TI  - Outcomes of total knee arthroplasty in degenerative osteoarthritic knee with genu
      recurvatum.
AB  - BACKGROUND: This study aimed to assess the incidence of genu recurvatum without
      neuromuscular disorders in knees that underwent navigation-assisted total knee
      arthroplasty (TKA), to evaluate short-term radiologic and clinical results of
      navigation-assisted TKA in genu recurvatum, and to evaluate differences in
      results according to the degree of pre-operative hyperextension and type of
      implant and insert. METHODS: This study retrospectively reviewed 510 knees that
      underwent navigation-assisted TKA from January 2005 to December 2011. The
      incidence of knees that showed hyperextension of >=5 degrees  (genu recurvatum)
      on navigation, and the accompanying alignment were evaluated. It assessed
      radiologic, intraoperative, and clinical results in recurvatum and control groups
      by using propensity score matching. RESULTS: A total of 465 knees underwent
      navigation-assisted TKA for degenerative osteoarthritis. Genu recurvatum was
      observed in 55 knees (11.8%). Of these, 41 knees (74.5%) had degree of
      hyperextension between five degrees and 10 degrees , and 47 (85.4%) had varus
      alignment. The thickness of the resected distal femur in the recurvatum group
      (7.6+/-1.6mm) was less than that in the control group (8.4+/-1.4mm, P=0.001). The
      thickness of the insert in the recurvatum group (12.5+/-2.3mm) was greater than
      in the control group (10.8+/-1.5mm, P<0.001). The sagittal alignment at the final
      follow-up was 1.3+/-3.4 degrees  in the control group and -0.1+/-0.7 degrees  in
      the recurvatum group (P=0.003). Subgroup analyses in the recurvatum group showed
      no significant difference in sagittal alignment and patient-related outcomes by
      degree of pre-operative hyperextension and implant/insert type (P>0.05 for all
      parameters). CONCLUSIONS: Genu recurvatum was not uncommon among patients
      undergoing primary TKA. This review obtained satisfactory short-term clinical and
      radiologic results, with a smaller distal femoral resection and thicker insert.

PMID- 29325838
TI  - Clinical and radiologic evaluation of medial epicondylar osteotomy for varus
      total knee arthroplasty.
AB  - BACKGROUND: In varus total knee arthroplasty (TKA), a pathologic contracture of
      the medial soft tissue should be released for ligament balancing. A medial
      epicondylar osteotomy has been performed as an alternative method for this. The
      purpose of this study was to demonstrate the clinical and radiologic results of
      medial epicondylar osteotomy for varus TKA, focusing on the union type of
      osteotomy site. METHODS: The study retrospectively evaluated 61 cases with a mean
      femorotibial angle of 10.4 degrees  varus and a mean flexion contracture angle of
      8.5+/-9.8 degrees . Intraoperative medial and lateral gap difference in extension
      and 90 degrees  flexion was accepted at <2mm. Clinical outcomes (Knee Society
      Scores, range of motion) and radiologic outcomes (coronal alignment and valgus
      stability) were compared between the two groups divided by the union type of
      osteotomy site (bony union or fibrous union). RESULTS: The clinical and
      radiologic outcomes were significantly improved at the latest follow-up. Bony
      union was achieved in 39 (63.9%) patients, whereas 22 patients showed fibrous
      union. There was no difference in the varus-valgus angle on the stress
      radiographs between the bony union and fibrous union group (1.6+/-1.2 degrees 
      vs. 1.6+/-0.8 degrees , P<0.916). The Knee Society Scores (knee, function), range
      of motion and radiographic alignment did not differ between the two groups.
      CONCLUSION: Medial epicondylar osteotomy was a good option for gap balancing
      during TKA, as it provided satisfactory clinical and radiological results,
      regardless of union type of the osteotomy site.

PMID- 29325839
TI  - The effect of low-load exercise on joint pain, function, and activities of daily
      living in patients with knee osteoarthritis.
AB  - BACKGROUND: Knee osteoarthritis has a lifetime risk of nearly one in two, with
      obese individuals being most susceptible. While exercise is universally
      recognized as a critical component for management, unsafe or ineffective exercise
      frequently leads to exacerbation of joint symptoms. AIM: Evaluate the effect of a
      12week lower body positive pressure (LBPP) supported low-load treadmill walking
      program on knee pain, joint function, and performance of daily activities in
      patients with knee osteoarthritis (OA). DESIGN: Prospective, observational,
      repeated measures investigation. SETTING: Community based, multidisciplinary
      musculoskeletal medicine clinic. PATIENTS: Thirty-one patients, aged 50-75, with
      a BMI >=25kg/m2 and radiographic confirmed mild to moderate knee OA.
      INTERVENTION: Twelve week LBPP treadmill walking exercise regimen. OUTCOME
      MEASURES: The Knee Injury and Osteoarthritis Outcome Score (KOOS) and the
      Canadian Occupational Performance Measure (COPM) were used to quantify joint
      symptoms and patient function; isokinetic thigh muscle strength was evaluated;
      and a 10-point VAS was used to quantify acute knee pain while walking. Baseline
      and follow-up data were compared in order to examine the effect of the 12week
      exercise intervention. RESULTS: There was a significant difference between
      baseline and follow-up data: KOOS and COPM scores both improved; thigh muscle
      strength increased; and acute knee pain during full weight bearing walking
      diminished significantly. CONCLUSIONS: Participation in a 12week LBPP supported
      treadmill walking exercise regimen significantly enhanced patient function and
      quality of life, as well as the ability to perform activities of daily living
      that patient's self-identified as being important, yet difficult to perform.

PMID- 29325840
TI  - Early comparative outcomes of unicompartmental and total knee arthroplasty in
      severely obese patients.
AB  - BACKGROUND: Medial unicompartmental knee arthroplasty (UKA) may have advantages
      over total knee arthroplasty (TKA) in the setting of obesity. There has been no
      direct comparison between the two cohorts. This study compares outcomes and
      complications of severely obese patients undergoing medial UKA versus TKA.
      METHODS: Six hundred and fifty medial UKA and 1300 TKA were performed in patients
      with BMI >35kg/m2 (mean 41kg/m2) between 2007 and 2012. Pre- and postoperative
      ROM, Knee Society scores, perioperative factors, complications and reoperations
      were compared. RESULTS: UKA patients had higher preoperative ROM, and Knee
      Society pain (KSP), functional (KSF), and clinical (KSC) scores (p<0.001,
      p=0.0008, p=0.0003, p=0.051 respectively). Mean tourniquet times, operative
      times, and lengths of stay were lower after UKA. Four TKA patients required
      transfusion. Mean follow-up was 2.3years. The frequency of manipulation under
      anesthesia was higher in TKA patients (p<0.001), while the rate of component
      revision was similar between the two groups (1.2% vs. 1.7%, p=0.328). Frequency
      of deep infection was lower in the UKA group (p=0.016). Postoperative KSF, change
      in KSF, and ROM were higher (p<0.0001) after UKA, but KSP and KSC were
      equivalent. CONCLUSIONS: Severely obese patients who underwent medial UKA
      demonstrated equal survivorship with substantially fewer reoperations, reduced
      deep infection, and less perioperative complications at short term follow-up.
      Severely obese patients had improved KSF scores and maintenance of ROM after UKA
      compared with TKA.

PMID- 29325841
TI  - Single-Center Experience With Venovenous ECMO for Influenza-Related ARDS.
AB  - OBJECTIVES: This study was designed to determine whether venovenous
      extracorporeal membrane oxygenation (VV ECMO) reduced mortality in patients with
      influenza-related acute respiratory distress syndrome (ARDS). DESIGN: A
      retrospective cohort study was performed. Baseline characteristics of
      participants were compared and Kaplan-Meier survival analysis was used to compare
      survival at last medical center follow-up. Cox proportional hazards modeling also
      was performed to test for univariate associations between salient variables and
      mortality. SETTING: A single-center ECMO referral university hospital.
      PARTICIPANTS: All patients admitted with influenza-related ARDS during the 2015
      to 2016 influenza season. INTERVENTIONS: Mechanical ventilation alone versus
      mechanical ventilation and ECMO cannulation. MEASUREMENTS AND MAIN RESULTS: A
      total of 26 patients with influenza-related ARDS were included in the cohort.
      Thirteen patients were treated with VV ECMO while 13 were not. Twelve of the ECMO
      patients and 8 of the non-ECMO patients were transferred from outside hospitals.
      Patients treated with ECMO were younger and had less hypertension and diabetes
      mellitus. There was no difference in baseline sequential organ failure assessment
      score between the 2 groups. In-hospital mortality for ECMO patients was 15.4%
      versus 46.7% for patients not treated with ECMO. Survival at last medical center
      follow-up was better in patients treated with ECMO (p = 0.02). Age, highest blood
      carbon dioxide level, and treatment without ECMO were all associated with
      increased mortality. CONCLUSIONS: Influenza-related ARDS has a high mortality
      rate and patients treated only with mechanical ventilation have worse outcome
      than those managed with VV ECMO. More liberal use of ECMO should be considered in
      patients with influenza-related ARDS.

PMID- 29325842
TI  - Use of Dexmedetomidine in Cardiothoracic and Vascular Anesthesia.
AB  - Dexmedetomidine is a highly selective alpha2-adrenergic agonist with analgesic
      and sedative properties. In the United States, the Food and Drug Administration
      approved the use of the drug for short-lasting sedation (24 h) in intensive care
      units (ICUs) in patients undergoing mechanical ventilation and endotracheal
      intubation. In October 2008, the Food and Drug Administration extended use of the
      drug for the sedation of nonintubated patients before and during surgical and
      nonsurgical procedures. In the European Union, the European Medicine Agency
      approved the use of dexmedetomidine in September 2011 with a single recognized
      indication: ICU adult patients requiring mild sedation and awakening in response
      to verbal stimulus. At present, the use of dexmedetomidine for sedation outside
      the ICU remains an off-label indication. The benefits of dexmedetomidine in
      critically ill patients and in cardiac, electrophysiology-related, vascular, and
      thoracic procedures are discussed.

PMID- 29325843
TI  - Preoperative Intra-Aortic Counterpulsation in Cardiac Surgery: Insights From a
      Retrospective Series of 588 Consecutive High-Risk Patients.
AB  - OBJECTIVE: To support a rational use of preoperative intra-aortic balloon pump
      (IABP) in cardiac surgery. DESIGN: Retrospective, observational study. SETTING:
      Single university hospital. PARTICIPANTS: The study included 588 (mean age 68.5
      +/- 9.6 yr) consecutive patients who received IABP before cardiac surgery from
      1999 to 2016. INTERVENTIONS: Coronary surgery was performed in 573 (97.4%) cases.
      IABP indications were prophylaxis (n = 147), unstable angina (n = 239), and rapid
      worsening of hemodynamics (n = 202). Baseline characteristics of patients were
      analyzed with multivariable methods. Comparison of outcomes postsurgery between
      74 patients undergoing IABP because of left main coronary artery disease (LMCAD)
      (stenosis >= 50%) and a new series of 1,360 patients experiencing LMCAD but who
      did not receive an IABP using propensity-score matching. MEASUREMENTS AND MAIN
      RESULTS: Throughout the study period, the rate of IABP use for prophylaxis and
      unstable angina increased (p = 0.0029) despite reduction in patient surgical risk
      (p = 0.0051). Early period of surgery (p = 0.032), rapid worsening of
      hemodynamics in the operating room (p = 0.0029), renal impairment (p < 0.0001),
      and ventilation before surgery (p = 0.0032) were predictors of in-hospital
      mortality. The cumulative rate of IABP-related complications was 6.8%. Current
      smoking (p = 0.025) and the use of a 9 Fr catheter (p = 0.0017) were predictors
      of IABP-related vascular complications. No difference was found regarding
      outcomes postsurgery for 43 pairs of IABP/non-IABP matched patients with LMCAD,
      even though preoperative IABP was associated with an increased use of bilateral
      internal thoracic artery grafting. CONCLUSIONS: Preoperative use of IABP in
      cardiac surgery was shown in this study to be safe, even for high-risk patients.
      LMCAD is not by itself a sufficient indication for prophylactic IABP.

PMID- 29325844
TI  - Naloxone Infusion During Thoracic Endovascular Aortic Aneurysm Repair to Prevent
      Spinal Cord Injury.

PMID- 29325845
TI  - Effect of Continuous Paravertebral Dexmedetomidine Administration on
      Intraoperative Anesthetic Drug Requirement and Post-Thoracotomy Pain Syndrome
      After Thoracotomy: A Randomized Controlled Trial.

PMID- 29325846
TI  - Hospital Outcome and Risk Indices of Mortality after redo-mitral valve surgery in
      Potential Candidates for Transcatheter Procedures: Results From a European
      Registry.
AB  - OBJECTIVE: Transcatheter mitral valve-in-valve/valve-in-ring procedures (TM
      VIVoR) are increasing. The authors aimed to identify independent predictors for
      hospital mortality in redo mitral valve surgery as possible future selection
      criteria for TM-VIVoR. DESIGN: Retrospective multicenter registry. SETTING:
      Tertiary university and community hospitals. PARTICIPANTS: Two-hundred and sixty
      patients (out of 920 enrolled) who are potentially candidates for TM-VIVoR
      undergoing redo-surgery. INTERVENTIONS: Redo mitral surgery. MEASUREMENTS AND
      MAIN RESULTS: Regression analyzes and receiver operating characteristic (ROC)
      curves identified independent predictors of death. Patients potentially
      candidates for TM-VIVoR reported significant hospital mortality (9.2%; EuroSCORE
      II: 13.2 +/- 13.1, Society of Thoracic Surgeons [STS] score: 6.2 +/- 3.1) and
      major morbidity (3.8% acute myocardial infarction, 5% stroke, 16.9% perioperative
      respiratory failure, 16.5% acute renal insufficiency, 25% massive transfusions).
      EuroSCORE II (odds ration [OR] 1.06; confidence interval [CI] 1.01-1.10; p =
      0.005), STS score (OR 1.58; CI 1.27-1.97; p = 0.001), age at surgery (OR 1.05; CI
      1.00-1.15; p = 0.05), preoperative dialysis (OR 2.5; CI 1.8-12.6; p = 0.042),
      left ventricular ejection fraction (LVEF) <30% (OR 4.8; CI 1.12-37.1; p = 0.021),
      severe pulmonary hypertension (OR 7.5; CI 1.9-29.4; p = 0.003), and previous
      coronary artery bypass grafting (CABG) (OR 11.8; CI 1.7-36.9; p = 0.002) were
      independent predictors of hospital mortality. ROC analyses reported good
      prediction for EuroSCORE II (AUC: 0.76; cut-off value: >13.1; 70.8% sensitivity
      and 68.2% specificity) and better prediction for STS score (AUC: 0.81; cut-off
      value: 7.4; 75.0% sensitivity and 66.2% specificity). Quintiles stratification
      identified EuroSCORE II >=18.7 (5th quintile, observed mortality: 19.3%) and STS
      score >9.1 as strong predictors of death within each risk-categorization (OR 5.9
      and 12.1, respectively). CONCLUSIONS: High EuroSCORE II and STS scores, advanced
      age at surgery, LVEF <30%, previous CABG, severe pulmonary hypertension or
      preoperative dialysis might represent in the future preferred indications for TM
      VIVoR in the redo-mitral surgery scenario.

PMID- 29325847
TI  - Amphetamine-Induced Striatal Dopamine Release Measured With an Agonist
      Radiotracer in Schizophrenia.
AB  - BACKGROUND: Receptor imaging studies have reported increased amphetamine-induced
      dopamine release in subjects with schizophrenia (SCH) relative to healthy control
      subjects (HCs). A limitation of these studies, performed with D2/3 antagonist
      radiotracers, is the failure to provide information about D2/3 receptors
      configured in a state of high affinity for the agonists (i.e., D2/3 receptors
      coupled to G proteins [D2/3 HIGH]). The endogenous agonist dopamine binds with
      preference to D2/3 HIGH receptors relative to D2/3 LOW receptors, making it
      critical to understand the status of D2/3 HIGH receptors in SCH. METHODS: D2/3
      agonist positron emission tomography radiotracer [11C]N-propyl-norapomorphine
      ([11C]NPA) binding potential (BPND) was measured in 14 off-medication subjects
      with SCH and 14 matched HCs at baseline and after the administration of 0.5 mg kg
      1 oral D-amphetamine. The amphetamine-induced change in BPND (DeltaBPND) was
      calculated as the difference between BPND in the postamphetamine condition and
      BPND in the baseline condition and was expressed as a percentage of BPND at
      baseline. RESULTS: A trend-level increase was observed in comparing baseline
      [11C]NPA BPND (repeated-measures analysis of variance, F1,26 = 3.34, p = .08)
      between the SCH and HC groups. Amphetamine administration significantly decreased
      BPND in all striatal regions across all subjects in both groups. No differences
      were observed in [11C]NPA DeltaBPND (repeated-measures analysis of variance,
      F1,26 = 1.9, p = .18) between HCs and subjects with SCH. Amphetamine
      significantly increased positive symptoms in subjects with SCH (19.5 +/- 5.3 vs.
      23.7 +/- 4.1, paired t test, p < .0001); however, no correlations were noted with
      [11C]NPA BPND or DeltaBPND. CONCLUSIONS: This study provides in vivo indication
      of a role for postsynaptic factors in amphetamine-induced psychosis in SCH.

PMID- 29325849
TI  - Coagonist of GLP-1 and glucagon decreases liver inflammation and atherosclerosis
      in dyslipidemic condition.
AB  - Dyslipidemia enhances progression of atherosclerosis. Coagonist of GLP-1 and
      glucagon are under clinical investigation for the treatment of obesity and
      diabetes. Earlier, we have observed that coagonist reduced circulating and
      hepatic lipids, independent of its anorexic effects. Here, we investigated the
      role of coagonist of GLP-1 and glucagon receptors in complications of diet
      induced dyslipidemia in hamsters and humanized double transgenic mice. Hamsters
      fed on high fat high cholesterol diet were treated for 8 weeks with coagonist of
      GLP-1 and glucagon receptors (75 and 150 MUg/kg). Pair-fed control was
      maintained. Cholesterol fed transgenic mice overexpressing hApoB100 and hCETP
      with coagonist (300 MUg/kg) for 4 weeks. After the completion of treatment,
      biochemical estimations were done. Coagonist treatment reduced triglycerides in
      plasma, liver and aorta, plasma cholesterol and hepatic triglyceride secretion
      rate. Expressions of HMG-CoA reductase and SBREBP-1C were reduced and expressions
      of LDLR, CYP7A1, ABCA1 and ABCB11 were increased in liver, due to coagonist
      treatment. Coagonist treatment increased bile flow rate and biliary cholesterol
      excretion. IL-6 and TNF-alpha were reduced in plasma and expression of TNF-alpha,
      MCP-1, MMP-9 and TIMP-1 decreased in liver. Treatment with coagonist reduced
      oxidative stress in liver and aorta. Energy expenditure was increased and
      respiratory quotient was reduced by coagonist treatment. These changes were
      correlated with reduced hepatic inflammation and lipids in liver and aorta in
      coagonist treated hamsters. Coagonist treatment also reduced lipids in
      cholesterol-fed transgenic mice. These changes were independent of glycaemia and
      anorexia observed after coagonist treatment. Long term treatment with coagonist
      of GLP-1 and glucagon receptor ameliorated diet-induced dyslipidemia and
      atherosclerosis by regulating bile homeostasis, liver inflammation and energy
      expenditure.

PMID- 29325850
TI  - Interaction of DNA with water soluble complex of Nickle and formation of DNA
      cross-links.
AB  - Interaction of double stranded DNA with bulky and hydrophobic Salen type Schiff
      base complex: [N, N' Bis [3- tert-butyl-5-[triphenyl-phosphonium - methyl] -
      salicylidene] 1,2 ethylene-diamine nickel(III) acetate (refer to Ni Salen
      complex) was extensively investigated using the spectroscopic techniques and gel
      electrophoresis. Absorption titration experiment showed the hypochromic effect
      and the significant red shift of the complex absorption. In competition
      experiments with ethidium bromide (EB), Ni Salen complex exhibited non
      competitive binding at high concentrations. UV-vis absorption and fluorescence
      emission data agreed on a binding constant of (1.64 +/- 0.01) MUM-1, thereby
      showing the strong interaction of the complex with DNA; also, a binding site size
      of 2.33 +/- 0.01 base pairs per complex was achieved. Thermal denaturation
      experiment showed that Tm of calf thymus-DNA was increased by approximately 10 
      degrees C at a molar ratio of the dye/base of 0.2. The CD spectra of DNA
      exhibited an increase in both positive and negative peaks without any shift in
      the position of bands upon addition of the complex. The amplitude of the LD
      spectra of DNA was decreased in the presence of the complex. Reduced linear
      dichroism (LDred) revealed that the transition moment of complex was parallel to
      the DNA helix axis. Gel electrophoresis experiments confirmed that Ni Salen
      complex had no nuclease/DNA cleaving activity; also, DNA-DNA cross links were
      formed at high concentrations of complex, leading to the aggregation of DNA.

PMID- 29325851
TI  - Microbial population changes in patients with medication-related osteonecrosis of
      the jaw treated with systemic antibiotics.
AB  - OBJECTIVE: This study aimed to investigate the bacterial population in patients
      with medication-related osteonecrosis of the jaw (MRONJ) after treatment with
      doxycycline and metronidazole. STUDY DESIGN: A total of 38 patients with MRONJ
      (age range 55-88, mean age 73 + 8.82 standard deviation) treated with doxycycline
      first and with metronidazole second were enrolled in this study. Two swabs were
      taken at the margin of the infected MRONJ lesion after applying pressure on the
      marginal mucosa, and visible pus was secreted. Real-time polymerase chain
      reaction was used to analyze 20 periopathogenic and commensal species and the
      total bacterial level. Bacterial counts were compared between antibiotic
      treatments and with a control group of orally healthy patients who didn't have
      periodontal pockets of more than 3 mm (n = 29) by means of a Mann-Whitney U test.
      Comparisons between the two antibiotic treatments were performed by a paired
      Wilcoxon signed rank test. RESULTS: The total bacterial level was significantly
      higher in the MRONJ patients treated with systemic antibiotics compared with the
      control group. However, significant lower bacterial amounts were found for 12 of
      the 20 investigated bacteria. We couldn't establish a significant advantage of
      metronidazole administration after doxycycline treatment. CONCLUSION: Our
      findings suggest that the total bacterial level in MRONJ patients is higher even
      when treated with systemic antibiotics. The significantly different bacterial
      amounts of the selected species suggest an alteration in the microbial
      population.

PMID- 29325852
TI  - Quality and readability of internet-based information on halitosis.
AB  - OBJECTIVE: To evaluate quality and readability of Internet-based information on
      halitosis. STUDY DESIGN: An Internet search through 3 engines (Google, Yahoo, and
      Bing) was done with the terms ("bad breath," "halitosis," "oral malodor," "foul
      breath," "mouth malodor," "breath malodor," "fetor ex ore," "fetor oris,"
      "ozostomia," and "stomatodysodia"). The first 50 websites from each engine
      resulting from each search term were screened. Included websites were evaluated
      using Health on the Net (HON) criteria, Journal of American Medical Association
      (JAMA) benchmarks, DISCERN, Ensuring Quality Information for Patients (EQIP),
      Flesch Reading Ease (FRE) score, and Flesch-Kincaid Grade level. RESULTS: A total
      of 101 websites were included. HON, DISCERN, EQIP, and FRE score were 42.9%,
      37.6%, 37.4%, and 51.9% of the maximum score, respectively. Fewer than 50% of
      sites displayed attribution, disclosure, and currency according to JAMA
      benchmarks. HON score, DISCERN score, and EQIP score had significant correlation
      with each other and were significantly higher in sites displaying the HON seal.
      CONCLUSION: The current quality and readability of informative websites on
      halitosis are generally low and poorly organized. Clinicians should be able to
      assess the Internet-based information on halitosis, as well as give accurate
      advice and guide patients concerning this issue.

PMID- 29325853
TI  - Relationship between sjogren syndrome and periodontal status: A systematic
      review.
AB  - OBJECTIVE: This study aimed to examine whether Sjogren syndrome (SS) is related
      to periodontal status. STUDY DESIGN: A systematic review was performed on the
      basis of PRISMA (PROSPERO: CRD42017055202). A search was performed in the
      PubMed/MEDLINE, LILACS, Web of Science, and Science Direct databases. Hand
      searches and review of the gray literature were also performed. Three researchers
      independently selected studies, extracted data, and assessed methodologic
      quality. Studies that correlated primary and/or secondary SS with plaque index,
      gingival index, probing depth, and bleeding on probing were included. The risk of
      bias was estimated on the basis of the Newcastle-Ottawa scale. RESULTS: Seventeen
      studies were included in the review and 9 included in the meta-analysis, with a
      total of 518 and 544 patients, with or without SS, respectively. The mean
      difference of plaque index (0.29; 95% confidence interval [CI] 0.17-0.41),
      gingival index (0.52; 95% CI 0.14-0.89), and bleeding on probing (9.92; 95% CI
      4.37-15.47) were larger in patients with SS than in controls. In primary SS
      (0.47; 95% CI 0.10-0.83) and secondary SS (0.74; 95% CI 0.10-1.38), only the mean
      gingival index was larger compared with that in control group. The majority of
      the included studies were judged as having a high risk of bias. CONCLUSIONS: The
      present review did not provide strong evidence that periodontal status is
      affected by SS.

PMID- 29325848
TI  - A Genetic Investigation of Sex Bias in the Prevalence of Attention
      Deficit/Hyperactivity Disorder.
AB  - BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) shows substantial
      heritability and is two to seven times more common in male individuals than in
      female individuals. We examined two putative genetic mechanisms underlying this
      sex bias: sex-specific heterogeneity and higher burden of risk in female cases.
      METHODS: We analyzed genome-wide autosomal common variants from the Psychiatric
      Genomics Consortium and iPSYCH Project (n = 20,183 cases, n = 35,191 controls)
      and Swedish population register data (n = 77,905 cases, n = 1,874,637 population
      controls). RESULTS: Genetic correlation analyses using two methods suggested near
      complete sharing of common variant effects across sexes, with rg estimates close
      to 1. Analyses of population data, however, indicated that female individuals
      with ADHD may be at especially high risk for certain comorbid developmental
      conditions (i.e., autism spectrum disorder and congenital malformations),
      potentially indicating some clinical and etiological heterogeneity. Polygenic
      risk score analysis did not support a higher burden of ADHD common risk variants
      in female cases (odds ratio [confidence interval] = 1.02 [0.98-1.06], p = .28).
      In contrast, epidemiological sibling analyses revealed that the siblings of
      female individuals with ADHD are at higher familial risk for ADHD than the
      siblings of affected male individuals (odds ratio [confidence interval] = 1.14
      [1.11-1.18], p = 1.5E-15). CONCLUSIONS: Overall, this study supports a greater
      familial burden of risk in female individuals with ADHD and some clinical and
      etiological heterogeneity, based on epidemiological analyses. However, molecular
      genetic analyses suggest that autosomal common variants largely do not explain
      the sex bias in ADHD prevalence.

PMID- 29325854
TI  - Considerations in the diagnosis of oral hairy leukoplakia-an institutional
      experience.
AB  - OBJECTIVE: We report here the 10-year experience with oral hairy leukoplakia
      (OHL) at the Division of Oral and Maxillofacial Pathology at the University of
      North Carolina at Chapel Hill, NC, USA. STUDY DESIGN: All the associated
      hematoxylin and eosin and Epstein-Barr virus encoding region in situ
      hybridization slides of OHL cases between January 1, 2008, and February 1, 2017,
      were retrieved and reviewed. Collected demographic characteristics, clinical
      presentation, medical and social histories were reviewed and reported. RESULTS:
      Six OHL cases with confirmed in situ hybridization showed predilection for the
      lateral tongue. The study included 3 females and 3 males (mean age 50.5 years;
      age range 29-70 years). One patient had known HIV-positive status before biopsy
      was performed. Three patients had reported a history of heavy smoking. Other
      medical conditions reported were history of breast cancer, a long history of
      corticosteroid inhaler use for asthma treatment, high cholesterol, diabetes, and
      hypertension. CONCLUSIONS: The findings of this study indicate the need to
      include OHL as a potential entity in the differential diagnosis of leukoplakic
      tongue lesions, regardless of the patient's HIV status. In addition, the presence
      of OHL in the patient requires investigation of various explanations for EBV
      infection, including immunosuppression caused by HIV infection or chronic steroid
      use.

PMID- 29325855
TI  - Gating of long-term potentiation (LTP) in the thalamocortical auditory system of
      rats by serotonergic (5-HT) receptors.
AB  - The neuromodulator serotonin (5-hydroxytryptamine, 5-HT) plays an important role
      in controlling the induction threshold and maintenance of long-term potentiation
      (LTP) in the visual cortex and hippocampus of rodents. Serotonergic fibers also
      innervate the rodent primary auditory cortex (A1), but the regulation of A1
      plasticity by 5-HT receptors (5-HTRs) is largely uncharted. Thus, we examined the
      role of several, predominant 5-HT receptor classes (5-HT1ARs, 5-HT2Rs, and 5
      HT3Rs) in gating in vivo LTP induction at A1 synapses of adult, urethane
      anesthetized rats. Theta-burst stimulation (TBS) applied to the medial geniculate
      nucleus resulted in successful LTP induction of field postsynaptic potentials
      (fPSPs) generated by excitation of thalamocortical and intracortical A1 synapses.
      Local application (by reverse microdialysis in A1) of the broad-acting 5-HTR
      antagonist methiothepin suppressed LTP at both thalamocortical and intracortical
      synapses. In fact, rather than LTP, TBS elicited long-term depression during
      methiothepin application, an effect that was mimicked by the selective 5-HT2R
      antagonist ketanserin, but not the 5-HT1AR blocker WAY 100635. Interestingly,
      antagonism of 5-HT3Rs by granisetron selectively blocked LTP at thalamocortical,
      but not intracortical A1 synapses. Further, in the absence of TBS, granisetron
      application resulted in a pronounced increase in fPSP amplitude, suggesting that
      5-HT3Rs play an important role in regulating baseline (non-potentiated)
      transmission at A1 synapses. Together, these results indicate that activation of
      5-HT2Rs and 5-HT3Rs, but not 5-HT1ARs, exerts a clear, facilitating effect on LTP
      induction at A1 synapses, allowing 5-HT to act as a powerful regulator of long
      term plasticity induction in the fully matured A1 of mammalian species.

PMID- 29325857
TI  - Prospective advances in fetal biomagnetometry - Challenges remain.

PMID- 29325856
TI  - Is insufficient pulmonary air support the cause of dysphonia in chronic
      obstructive pulmonary disease?
AB  - OBJECTIVE: Optimal pulmonary air support is essential pre-requisite for efficient
      phonation. The objective is to correlate pulmonary and vocal functions in chronic
      obstructive pulmonary disease (COPD) to find out whether the reduced pulmonary
      function per se could induce dysphonia. METHODS: In this prospective case-control
      study, sixty subjects with stable COPD underwent evaluation of pulmonary and
      vocal functions. The pulmonary functions measured include {Forced vital capacity
      (FVC), forced expiratory volume in the first second (FEV1), FEV1/FVC ratio, peak
      expiratory flow (PEF), maximum mid-expiratory flow (MMEF)}. The vocal functions
      were {jitter, shimmer, noise-to-harmonic ratio, pitch perturbation quotient,
      amplitude perturbation quotient, maximum phonation time (MPT), sound pressure
      level, phonatory efficiency, resistance and power. A control group (n=35)
      underwent the same measurements. These functions were compared between subjects
      and controls. Also, correlation of the vocal and pulmonary functions was
      conducted. RESULTS: Thirty five (58.3%) of COPD subjects have dysphonia. The
      pulmonary functions were lower in all COPD group than in the control group
      (P<0.001 for all parameters). Also, the FVC, FEV1, PEF and MMEF % of predicted
      values were significantly lower in subjects with dysphonia (n=35) than those
      without dysphonia (n=25) with P values 0.0018, <0.001, 0.0011 and 0.0026
      respectively. In addition, the MPT in all subjects showed positive correlations
      to the 5 pulmonary functions (P=0.004 for FEV1/FVC ratio and P<0.001 for the
      rest). Also, the phonatory efficiency showed significant positive correlations
      with the pulmonary functions FVC, FEV1, PEF and MMEF (P=0.001, 0.001, 0.002 and
      0.001 respectively). Unlike efficiency, the phonatory resistance revealed
      significant negative correlations with these pulmonary functions in the same
      order (P=0.001, 0.003, 0.002, 0.001 respectively). CONCLUSION: Dysphonia is a
      common comorbidity with COPD which attributed to multifactorial etiologies. The
      lower the pulmonary function in COPD patients is the more likely to have
      dysphonia. Decreased pulmonary function was associated with reduced MPT and
      phonatory efficiency but with increased phonatory resistance. The reduced
      pulmonary functions in COPD can be the underlying cause of the altered vocal
      function and dysphonia. Great part of this dysphonia is functional, and hence,
      can be corrected by voice therapy in compensated subjects. Further researches are
      needed to evaluate the efficacy of voice therapy in these patients.

PMID- 29325858
TI  - Can clinical neurophysiology assist in patient selection for DBS in pediatric
      dystonia?

PMID- 29325859
TI  - Ki-67 Expression as a Factor Predicting Recurrence of Ductal Carcinoma In Situ of
      the Breast: A Systematic Review and Meta-Analysis.
AB  - BACKGROUND: Ki-67 is a marker of proliferating cells; in this meta-analysis we
      aimed to examine whether Ki-67 expression can predict recurrence rates of breast
      ductal carcinoma in situ (DCIS). MATERIALS AND METHODS: This systematic review
      and meta-analysis was performed according to the Preferred Reporting Items for
      Systematic Reviews and Meta-Analyses guidelines. Eligible articles were sought in
      MEDLINE up to April 30, 2017. Random effects (DerSimonian-Laird) models were used
      for the calculation of pooled relative risk (RR) estimates; meta-regression
      analysis was also performed. Separate analyses were performed according to Ki-67
      expression cutoff levels, invasiveness of recurrence, and adjustment of studies.
      RESULTS: Ten eligible cohort studies were synthesized; a significant association
      between Ki-67 expression and DCIS recurrence was noted for the Ki-67 cutoff at
      10% (RR = 1.66; 95% confidence interval [CI], 1.14-2.42) as well as the Ki-67
      cutoff at 14% (RR = 1.67; 95% CI, 1.01-2.77). Subanalysis on unadjusted (RR =
      1.48; 95% CI, 1.06-2.07) and adjusted studies (RR = 2.19; 95% CI, 1.42-3.38)
      replicated the statistically significant findings. Ki-67 expression predicted the
      risk of invasive (RR = 1.53; 95% CI, 1.14-2.06) and noninvasive (RR = 1.59; 95%
      CI, 1.19-2.13) recurrence. CONCLUSION: This meta-analysis highlights Ki-67
      expression as a predictor of DCIS recurrence; nevertheless, additional adjusted
      studies, with adequate follow-up periods, stemming from various world regions
      seem to be needed on this topic.

PMID- 29325860
TI  - BRCA2 Reversion Mutation Associated With Acquired Resistance to Olaparib in
      Estrogen Receptor-positive Breast Cancer Detected by Genomic Profiling of Tissue
      and Liquid Biopsy.

PMID- 29325861
TI  - Crystallographic and morphological analysis of sandblasted highly translucent
      dental zirconia.
AB  - OBJECTIVE: To assess the influence of alumina sandblasting on four highly
      translucent dental zirconia grades. METHODS: Fully sintered zirconia disk-shaped
      specimens (15-mm diameter; 0.5-mm thickness) of four highly translucent yttria
      partially stabilized zirconia (Y-PSZ) grades (KATANA HT, KATANA STML, KATANA
      UTML, Kuraray Noritake; Zpex Smile, Tosoh) were sandblasted with 50-MUm alumina
      (Al2O3) sand (Kulzer) or left 'as-sintered' (control) (n=5). For each zirconia
      grade, the translucency was measured using a colorimeter. Surface roughness was
      assessed using 3D confocal laser microscopy, upon which the zirconia grades were
      statistically compared for surface roughness using a Kruskal-Wallis test (n=10).
      X-ray diffraction (XRD) with Rietveld analysis was used to assess the zirconia
      phase composition. Micro-Raman spectroscopy was used to assess the potentially
      induced residual stress. RESULTS: The translucency of KATANA UTML was the highest
      (36.7+/-1.8), whereas that of KATANA HT was the lowest (29.5+/-0.9). The 'Al2O3
      sandblasted' and 'as-sintered' zirconia revealed comparable surface-roughness Sa
      values. Regarding zirconia-phase composition, XRD with Rietveld analysis revealed
      that the 'as-sintered' KATANA UTML contained the highest amount of cubic zirconia
      (c-ZrO2) phase (71wt%), while KATANA HT had the lowest amount of c-ZrO2 phase
      (41wt%). KATANA STML and Zpex Smile had a comparable zirconia-phase composition
      (60wt% c-ZrO2 phase). After Al2O3-sandblasting, a significant amount (over 25wt%)
      of rhombohedral zirconia (r-ZrO2) phase was detected for all highly translucent
      zirconia grades. SIGNIFICANCE: Al2O3-sandblasting did not affect the surface
      roughness of the three highly translucent Y-PSZ zirconia grades, but it changed
      its phase composition.

PMID- 29325862
TI  - Antibacterial effects of cinnamon (Cinnamomum zeylanicum) bark essential oil on
      Porphyromonas gingivalis.
AB  - The objective of this study was to investigate the antibacterial effects of
      cinnamon (Cinnamomum zeylanicum) bark essential oil (CBEO) and its principal
      constituent cinnamaldehyde against Porphyromonas gingivalis and to elucidate the
      antibacterial mechanism. GC-MS analysis showed that cinnamaldehyde was the major
      constituent in CBEO (57.97%). The minimum inhibition concentrations (MICs) of
      CBEO and cinnamaldehyde were 6.25 MUg/mL and 2.5 MUM for P. gingivalis,
      respectively. Nucleic acid and protein leakage was observed with increasing
      concentrations of CBEO and cinnamaldehyde. Additionally, propidium iodide uptake
      assays revealed CBEO and cinnamaldehyde at 1 * MIC impaired P. gingivalis
      membrane integrity by enhancing cell permeability. Morphological changes in P.
      gingivalis cells were observed by scanning electron microscopy, which indicated
      cell membrane destruction. To further determine the anti-biofilm effect, relative
      biofilm formation and established biofilms were examined, which demonstrated that
      both CBEO and cinnamaldehyde at sub-MIC levels inhibited P. gingivalis biofilm
      formation by 74.5% and 67.3% separately, but only CBEO slightly decreased
      established biofilms by 33.5% at 4 * MIC. These results suggest the potential of
      CBEO as a natural antimicrobial agent against periodontal disease. Furthermore,
      cinnamaldehyde was confirmed to be the antibacterial substance of CBEO with
      inhibitory action against P. gingivalis.

PMID- 29325863
TI  - High flux isothermal assays on pathogenic, virulent and toxic genetics from
      various pathogens.
AB  - Toxins, encoding by virulence factors, are significant cause of food-borne
      illnesses and death in the worldwide. Loop-mediated isothermal amplification
      (LAMP) is one of the widely used methodologies because of the high sensitivity,
      specificity and rapidity. Nowadays, LAMP has been regarded as an innovative gene
      amplification technology and emerged as an alternative to PCR-based methodologies
      in identification of the pathogenic virulent and toxic genetics. The high
      sensitivity of LAMP enables detection of the pathogens in sample materials even
      without time consuming and sample preparation. Therefore, we review the typical
      characteristics of LAMP assay, recent advance in detection of virulence factors
      and the application of LAMP assay on detection of four commonly virulence
      factors. As concluded, with the advantages of rapidity, simplicity, sensitivity,
      specificity and robustness, LAMP is capable of identification the virulence
      factors. Moreover, the main purpose of this review is to provide theory support
      for the application of LAMP assay on the virulence factors identification.

PMID- 29325864
TI  - Infections, genetic and environmental factors in pathogenesis of autoimmune
      thyroid diseases.
AB  - In Autoimmune disease a combination of infection, genetic and environmental
      factors causes an autoimmune response to the thyroid gland (characterized by
      lymphocytic infiltrations), thyroid stimulating hormone receptor (TSHR) and
      different thyroid antigens. Graves' and Hashimoto disease are autoimmune
      disorders with genetic predisposition. CD40 that stimulates the proliferation and
      differentiation of lymphocytes is an essential immunomodulatory component for
      follicular cells in the thyroid and the cell that present the antigen. CD40,
      PTPN22 and thyroid-specific genes are immunomodulating genes for the TSH receptor
      and thyroglobulin. CD40 used to be associated with Graves's disease as positional
      candidate on the basis of Graves' disease linkage study connecting with 20q11
      genome chromosomal region. The PTPN22 gene gives rise to a substantial risk of
      specific autoimmune phenotypes and frequent disease mechanisms. Infections have
      been implicated in the pathogenesis of AITD including Coxsackie virus, Yersinia
      enterocolitica, Borrelia burgdorferi, Helicobacter pylori and retroviruses (HTLV
      1, HFV, HIV and SV40). Infectious hepatitis C agents are the strongest proof
      supporting an affiliation with AITD. The essential environmental triggers of AITD
      are iodine, drugs, infection, smoking and perhaps stress. Autoimmune disease
      provide important facts on genetic mechanisms that influence the prognosis and
      treatment of the disease and by recent molecular techniques through gene
      expression study by quantitative Real Time-PCR and microarray, we can identify
      novel genes which are responsible for Graves' and Hashimoto disease.

PMID- 29325865
TI  - Emerging discrepancies in conventional and molecular epidemiology of methicillin
      resistant Staphylococcus aureus isolated from bovine milk.
AB  - Methicillin resistant Staphylococcus aureus (MRSA) is an emerging public health
      concern from dairy milk, and its diagnosis by phenotypic methodology is
      experiencing higher discrepancies. The present study was planned to estimate
      discrepancies in phenotypic identification of MRSA and MSSA (Methicillin
      sensitive Staphylococcus aureus) in relation to mecA, and prevalent risk factors
      from various localities. In-vitro oxacilline antibiotic disks were used for
      phenotypic identification of MRSA, whereas mecA gene was used as MRSA marker in
      Staph aureus by PCR. Total of 900 bovine milk samples from private and public
      farms located in district Faisalabad using convinent sampling technique were
      collected. Potential risk factors for MRSA prevalence identified by non
      parametric statistical tests were compared among different subdistricts.
      Discrepancy in MRSA was calculated as percentage of mecA negative strains while
      that of MSSA was determined as percentage of mecA positive strains. Molecular
      identification presented 17.97% (55/306) of discrepancy in MRSA in terms of
      negative mecA strains from district Faisalabad while sub-district Faisalabad, sub
      district Jaranwala, and sub-district Samundary presented 13.98% (13/93), 18.28%
      (17/93), and 20.83% (25/120) discrepant results, respectively. On the other hand,
      29.1% (55/189) of discrepancy in MSSA in terms of mecA positive strains from MSSA
      isolates was noted. MSSA results were more discrepant than that of MRSA. Hence
      discrepancy ratio of MSSA over MRSA was noted to be 1.53, 1.50, and 1.21 from
      tehsil Faislabad, Samundary, and Jaranwala. Tick infestation, lactation stage,
      frequency of milking, dirty milker's hands, unhygienic milking procedures, and
      higher use of beta lactam of antibiotics were risk factors that were prevalent in
      increasing order from sub-district Faisalabad > Jaranwala > Samundary. The study
      concluded higher prevalence of MRSA in bovine milk samples, and found remarkable
      discrepancies in phenotypic and genotypic identification which demand immediate
      attention to tackle exacerbation in resistance patterns.

PMID- 29325866
TI  - 2-(2-Nitrovinyl) furan exacerbates oxidative stress response of Escherichia coli
      to bacteriostatic and bactericidal antibiotics.
AB  - The influence of 2-(2-nitrovinyl) furan on the activities of selected
      bacteriostatic and bactericidal antibiotics was investigated. Minimum inhibitory
      concentration and fractional inhibitory concentration index were determined to
      evaluate the interaction between 2-(2-nitrovinyl) furan and the antibiotics. 2-(2
      nitrovinyl) furan exhibited additive interactions with chloramphenicol,
      erythromycin, lincomycin and gemifloxacin. However, synergistic interaction was
      observed with amoxicillin, ampicillin and ciprofloxacin. Superoxide anion content
      of Escherichia coli exposed to antibiotics with/without 2-(2-nitrovinyl) furan
      increased significantly (p < .05). Furthermore, reduced glutathione decreased
      significantly with a corresponding increase in glutathione disulphide. In
      addition, malondialdehyde, a product of lipid peroxidation, increased
      significantly in E. coli exposed to antibiotics and 2-(2-nitrovinyl) furan. It
      can be deduced from this study that 2-(2-nitrovinyl) furan enhanced
      bacteriostatic and bactericidal antibiotics-mediated bacterial death possibly by
      potentiating reactive oxygen species generation and oxidative stress.

PMID- 29325869
TI  - Microglial activation and the nitric oxide/cGMP/PKG pathway underlie enhanced
      neuronal vulnerability to mitochondrial dysfunction in experimental multiple
      sclerosis.
AB  - During multiple sclerosis (MS), a close link has been demonstrated to occur
      between inflammation and neuro-axonal degeneration, leading to the hypothesis
      that immune mechanisms may promote neurodegeneration, leading to irreversible
      disease progression. Energy deficits and inflammation-driven mitochondrial
      dysfunction seem to be involved in this process. In this work we investigated, by
      the use of striatal electrophysiological field-potential recordings, if the
      inflammatory process associated with experimental autoimmune encephalomyelitis
      (EAE) is able to influence neuronal vulnerability to the blockade of
      mitochondrial complex IV, a crucial component for mitochondrial activity
      responsible of about 90% of total cellular oxygen consumption. We showed that
      during the acute relapsing phase of EAE, neuronal susceptibility to mitochondrial
      complex IV inhibition is markedly enhanced. This detrimental effect was
      counteracted by the pharmacological inhibition of microglia, of nitric oxide (NO)
      synthesis and its intracellular pathway (involving soluble guanylyl cyclase, sGC,
      and protein kinase G, PKG). The obtained results suggest that mitochondrial
      complex IV exerts an important role in maintaining neuronal energetic homeostasis
      during EAE. The pathological processes associated with experimental MS, and in
      particular the activation of microglia and of the NO pathway, lead to an
      increased neuronal vulnerability to mitochondrial complex IV inhibition,
      representing promising pharmacological targets.

PMID- 29325867
TI  - Atypical antipsychotics, insulin resistance and weight; a meta-analysis of
      healthy volunteer studies.
AB  - Atypical antipsychotics increase the risk of diabetes and cardiovascular disease
      through their side effects of insulin resistance and weight gain. The populations
      for which atypical antipsychotics are used carry a baseline risk of metabolic
      dysregulation prior to medication which has made it difficult to fully understand
      whether atypical antipsychotics cause insulin resistance and weight gain
      directly. The purpose of this work was to conduct a systematic review and meta
      analysis of atypical antipsychotic trials in healthy volunteers to better
      understand their effects on insulin sensitivity and weight gain. Furthermore, we
      aimed to evaluate the occurrence of insulin resistance with or without weight
      gain and with treatment length by using subgroup and meta-regression techniques.
      Overall, the meta-analysis provides evidence that atypical antipsychotics
      decrease insulin sensitivity (standardized mean difference=-0.437, p<0.001) and
      increase weight (standardized mean difference=0.591, p<0.001) in healthy
      volunteers. It was found that decreases in insulin sensitivity were potentially
      dependent on treatment length but not weight gain. Decreases in insulin
      sensitivity occurred in multi-dose studies <13days while weight gain occurred in
      studies 14days and longer (max 28days). These findings provide preliminary
      evidence that atypical antipsychotics cause insulin resistance and weight gain
      directly, independent of psychiatric disease and may be associated with length of
      treatment. Further, well-designed studies to assess the co-occurrence of insulin
      resistance and weight gain and to understand the mechanisms and sequence by which
      they occur are required.

PMID- 29325868
TI  - A Canadian genome-wide association study and meta-analysis confirm HLA as a risk
      factor for peanut allergy independent of asthma.

PMID- 29325870
TI  - Impact of an infectious disease specialist on antifungal use: an interrupted time
      series analysis in a tertiary hospital in Tokyo.
AB  - BACKGROUND: Antimicrobial stewardship programmes are considered essential for
      optimizing antimicrobial use in order to improve patient outcomes, reduce the
      number of adverse sequelae, prevent resistance, and ensure cost-effective
      therapy. AIM: To assess the efficacy and the limitations of antifungal
      antimicrobial stewardship programmes. METHODS: A bundle to manage infectious
      diseases was implemented in our hospital in October 2010. Data regarding
      antimicrobial use density (AUD) from April 2006 to May 2016 were collected.
      Trends in AUD were assessed using an interrupted time-series model for three
      separate periods: the pre-bundle, the bundle implementation, and the long-term
      follow-up periods. The primary and secondary outcomes were AUD (defined daily
      dose (DDD) per 1000 patient-days) of intravenous antifungals and expenditure on
      antifungals per fiscal year, respectively. FINDINGS: The AUD for all intravenous
      antifungals decreased from 26.1 in 2006 to 9.9 in 2015. Whereas the change in the
      trend during the pre-bundle period was not significant (slope: 0.062; 95%
      confidence interval (CI): -0.180 to 0.305), a significant decrease was observed
      in the bundle implementation period (slope: -0.535; 95% CI: -0.907 to -0.164).
      The trend slowed during the long-term follow-up period (slope: -0.040; 95% CI: 
      0.218 to 0.138). Total expenditure on antifungals decreased by 73%, from
      Y52,354,411 in fiscal year 2006 to Y14,073,099 in fiscal year 2015. CONCLUSION:
      The bundle significantly reduced the use of antifungals and decreased costs over
      time, but this effect was limited in that it had stabilized within three years.

PMID- 29325871
TI  - Use of ultraviolet-fluorescence-based simulation in evaluation of personal
      protective equipment worn for first assessment and care of a patient with
      suspected high-consequence infectious disease.
AB  - BACKGROUND: Variations currently exist across the UK in the choice of personal
      protective equipment (PPE) used by healthcare workers when caring for patients
      with suspected high-consequence infectious diseases (HCIDs). AIM: To test the
      protection afforded to healthcare workers by current PPE ensembles during
      assessment of a suspected HCID case, and to provide an evidence base to justify
      proposal of a unified PPE ensemble for healthcare workers across the UK. METHODS:
      One 'basic level' (enhanced precautions) PPE ensemble and five 'suspected case'
      PPE ensembles were evaluated in volunteer trials using 'Violet'; an ultraviolet
      fluorescence-based simulation exercise to visualize exposure/contamination
      events. Contamination was photographed and mapped. FINDINGS: There were 147 post
      simulation and 31 post-doffing contamination events, from a maximum of 980, when
      evaluating the basic level of PPE. Therefore, this PPE ensemble did not afford
      adequate protection, primarily due to direct contamination of exposed areas of
      the skin. For the five suspected case ensembles, 1584 post-simulation
      contamination events were recorded, from a maximum of 5110. Twelve post-doffing
      contamination events were also observed (face, two events; neck, one event;
      forearm, one event; lower legs, eight events). CONCLUSION: All suspected case PPE
      ensembles either had post-doffing contamination events or other significant
      disadvantages to their use. This identified the need to design a unified PPE
      ensemble and doffing procedure, incorporating the most protective PPE considered
      for each body area. This work has been presented to, and reviewed by, key
      stakeholders to decide on a proposed unified ensemble, subject to further
      evaluation.

PMID- 29325872
TI  - Structure and function of a highly active Bile Salt Hydrolase (BSH) from
      Enterococcus faecalis and post-translational processing of BSH enzymes.
AB  - Bile Salt Hydrolase (BSH), a member of Cholylglycine hydrolase family, catalyzes
      the de-conjugation of bile acids and is evolutionarily related to penicillin V
      acylase (PVA) that hydrolyses a different substrate such as penicillin V. We
      report the three-dimensional structure of a BSH enzyme from the Gram-positive
      bacteria Enterococcus faecalis (EfBSH) which has manifold higher hydrolase
      activity compared to other known BSHs and displays unique allosteric catalytic
      property. The structural analysis revealed reduced secondary structure content
      compared to other known BSH structures, particularly devoid of an anti-parallel
      beta-sheet in the assembly loop and part of a beta-strand is converted to
      increase the length of a substrate binding loop 2. The analysis of the substrate
      binding pocket showed reduced volume owing to altered loop conformations and
      increased hydrophobicity contributed by a higher ratio of hydrophobic to
      hydrophilic groups present. The aromatic residues F18, Y20 and F65 participate in
      substrate binding. Thus, their mutation affects enzyme activity. Docking and
      Molecular Dynamics simulation studies showed effective polar complementarity
      present for the three hydroxyl (-OH) groups of GCA substrate in the binding site
      contributing to higher substrate specificity and efficient catalysis. These are
      unique features characteristics of this BSH enzyme and thought to contribute to
      its higher activity and specificity towards bile salts as well as allosteric
      effects. Further, mechanism of autocatalytic processing of Cholylglycine
      Hydrolases by the excision of an N-terminal Pre-peptide was examined by inserting
      different N-terminal pre-peptides in EfBSH sequence. The results suggest that two
      serine residues next to nucleophile cysteine are essential for autocalytic
      processing to remove precursor peptide. Since pre-peptide is absent in EfBSH the
      mutation of these serines is tolerated. This suggests that an evolution-mediated
      subordination of the pre-peptide excision site resulted in loss of pre-peptide in
      EfBSH and other related Cholylglycine hydrolases.

PMID- 29325873
TI  - Auditory sensory gating predicts acceptable noise level.

PMID- 29325874
TI  - Perceptual changes with monopolar and phantom electrode stimulation.
AB  - Phantom electrode (PE) stimulation is achieved by simultaneously stimulating out
      of-phase from two adjacent intra-cochlear electrodes with different amplitudes.
      If the basal electrode stimulates with a smaller amplitude than the apical
      electrode of the pair, the resulting electrical field is pushed away from the
      basal electrode producing a lower pitch. There is great interest in using PE
      stimulation in a processing strategy as it can be used to provide stimulation to
      regions of the cochlea located more apically than the most apical contact on the
      electrode array. The result is that even lower pitch sensations can be provided
      without additional risk of a deeper insertion. However, it is unknown if there
      are perceptual differences between monopolar (MP) and PE stimulation other than a
      shift in place pitch. Furthermore, it is unknown if the effect and magnitude of
      changing from MP to PE stimulation is dependent on electrode location. This study
      investigates the perceptual differences (including pitch and other sound quality
      differences) at multiple electrode positions using MP and PE stimulation using
      both a multidimensional scaling procedure (MDS) and a traditional scaling
      procedure. 10 Advanced Bionics users reported the perceptual distances between 5
      single electrode (typically 1, 3, 5, 7, and 9) stimuli in either MP or PE (sigma
      = 0.5) mode. Subjects were asked to report how perceptually different each pair
      of stimuli were using any perceived differences except loudness. Subsequently,
      each stimulus was presented in isolation and subjects scaled how "high" or how
      "clean" each sounded. Results from the MDS task suggest that perceptual
      differences between MP and PE stimulation can be explained by a single dimension.
      The traditional scaling suggests that the single dimension is place pitch. PE
      stimulation elicits lower pitch perceptions in all cochlear regions. Analysis of
      Cone Beam Computer Tomography (CBCT) data suggests that PE stimulation may be
      more effective at the apical part of the cochlea. PE stimulation can be used for
      new sound coding strategies in order to extend the pitch range for cochlear
      implant (CI) users without perceptual side effects.

PMID- 29325875
TI  - Fatal thoracic empyema involving Campylobacter rectus: A case report.
AB  - We report the case of a 69-year-old man admitted for septic shock secondary to
      necrotic pneumoniae complicated by thoracic empyema of fatal issue.
      Microbiological examination of pleural liquid revealed a mixed anaerobic flora
      involving Campylobacter rectus and Actinomyces meyeri. Campylobacter rectus is an
      infrequent anaerobic pathogen of oral origin To our knowledge, this is the first
      case report of fatal C. rectus - associated thoracic empyema, and only the second
      reported case in which identification was successfully performed by MALDI-TOF MS.

PMID- 29325876
TI  - Nogo-A interacts with TrkA to alter nerve growth factor signaling in Nogo-A
      overexpressing PC12 cells.
AB  - The Nogo-A protein, originally discovered as a potent myelin-associated inhibitor
      of neurite outgrowth, is also expressed by certain neurons, especially during
      development and after injury, but its role in neuronal function is not completely
      known. In this report, we overexpressed Nogo-A in PC12 cells to use as a model to
      identify potential neuronal signaling pathways affected by endogenously expressed
      Nogo-A. Unexpectedly, our results show that viability of Nogo-A-overexpressing
      cells was reduced progressively due to apoptotic cell death following NGF
      treatment, but only after 24 h. Inhibitors of neutral sphingomyelinase prevented
      this loss of viability, suggesting that NGF induced the activation of a ceramide
      dependent cell death pathway. Nogo-A over-expression also changed NGF-induced
      phosphorylation of TrkA at tyrosines 490 and 674/675 from sustained to transient,
      and prevented the regulated intramembrane proteolysis of p75NTR, indicating that
      Nogo-A was altering the function of the two neurotrophin receptors. Co
      immunoprecipitation studies revealed that there was a physical association
      between TrkA and Nogo-A which appeared to be dependent on interactions in the
      Nogo-A-specific region of the protein. Taken together, our results indicate that
      Nogo-A influences NGF-mediated mechanisms involving the activation of TrkA and
      its interaction with p75NTR.

PMID- 29325878
TI  - Can We Identify Futility in Kids? An Evaluation of Admission Parameters
      Predicting 100% Mortality in 1,292 Severely Injured Children.
AB  - BACKGROUND: Objective parameters predicting futility of care in severely injured
      pediatric patients are lacking. Although futility of care has been investigated
      in a limited number of studies in trauma patients, none of these studies achieves
      a 100% success rate in a large cohort of pediatric patients. The purpose of the
      current study was to identify extreme laboratory values that could be used to
      predict 100% mortality in severely injured children. STUDY DESIGN: We evaluated a
      registry-based, historical cohort of all severely injured children (Level I
      trauma, younger than 16 years old) who were not dead on arrival between January
      2010 and December 2016 from a single Level I trauma center. Extreme arrival
      laboratory data were evaluated both alone and in conjunction with traumatic brain
      injury. RESULTS: There were 1,292 patients who met inclusion criteria, of which
      1,169 (90.5%) survived and 123 (9.5%) died. Those who died were significantly
      younger, with higher head Abbreviated Injury Scale scores and overall Injury
      Severity Scores. Single extreme laboratory values were identified that predicted
      mortality perfectly (100% positive predictive value): international normalized
      ratio >=3.0, pH <=6.95, base excess <= -22, platelet count <=30,000, hemoglobin
      <=5.0 g/dL, rapid thromboelastography <=30 mm, and rapid thromboelastography
      lysis at 30 minutes >=50%. When 2 laboratory values or the presence of traumatic
      brain injury were added, lower thresholds for futility were noted. CONCLUSIONS:
      Extreme admission laboratory values are capable of predicting 100% mortality and
      futility of additional care in severely injured children with a high level of
      accuracy. Validation of these single-center findings is warranted and, if
      supported, should initiate a discussion within the pediatric trauma community
      about application and cessation of resuscitation efforts to optimize resource
      use.

PMID- 29325877
TI  - DmCatD, a cathepsin D-like peptidase of the hematophagous insect Dipetalogaster
      maxima (Hemiptera: Reduviidae): Purification, bioinformatic analyses and the
      significance of its interaction with lipophorin in the internalization by
      developing oocytes.
AB  - DmCatD, a cathepsin D-like peptidase of the hematophagous insect Dipetalogaster
      maxima, is synthesized by the fat body and the ovary and functions as yolk
      protein precursor. Functionally, DmCatD is involved in vitellin proteolysis. In
      this work, we purified and sequenced DmCatD, performed bioinformatic analyses and
      investigated the events involved in its targeting and storage in developing
      oocytes. By ion exchange and gel filtration chromatography, DmCatD was purified
      from egg homogenates and its identity was confirmed by mass spectrometry.
      Approximately 73% of the full-length transcript was sequenced. The phylogeny
      indicated that DmCatD has features which suggest its distancing from "classical"
      cathepsins D. Bioinformatic analyses using a chimeric construct were employed to
      predict post-translational modifications. Structural modeling showed that DmCatD
      exhibited the expected folding for this type of enzyme, and an active site with
      conserved architecture. The interaction between DmCatD and lipophorin in the
      hemolymph was demonstrated by co-immunoprecipitation. Colocalization of both
      proteins in developing oocyte membranes and yolk bodies was detected by
      immunofluorescence. Docking assays favoring the interaction DmCatD-lipophorin
      were carried out after modeling lipophorin of a related triatomine species. Our
      results suggest that lipophorin acts as a carrier for DmCatD to facilitate its
      further internalization by the oocytes. The mechanisms involved in the uptake of
      peptidases within the oocytes of insects have not been reported. This is the
      first experimental work supporting the interaction between cathepsin D and
      lipophorin in an insect species, enabling us to propose a pathway for its
      targeting and storage in developing oocytes.

PMID- 29325879
TI  - Ovarian control and monitoring in amphibians.
AB  - Amphibian evolution spans over 350 million years, consequently this taxonomic
      group displays a wide, complex array of physiological adaptations and their
      diverse modes of reproduction are a prime example. Reproduction can be affected
      by taxonomy, geographic and altitudinal distribution, and environmental factors.
      With some exceptions, amphibians can be categorized into discontinuous (strictly
      seasonal) and continuous breeders. Temperature and its close association with
      other proximate and genetic factors control reproduction via a tight relationship
      with circadian rhythms which drive genetic and hormonal responses to the
      environment. In recent times, the relationship of proximate factors and
      reproduction has directly or indirectly lead to the decline of this taxonomic
      group. Conservationists are tackling the rapid loss of species through a wide
      range of approaches including captive rescue. However, there is still much to be
      learned about the mechanisms of reproductive control and its requirements in
      order to fabricate species-appropriate captive environments that address a
      variety of reproductive strategies. As with other taxonomic groups, assisted
      reproductive technologies and other reproductive monitoring tools such as
      ultrasound, hormone analysis and body condition indices can assist
      conservationists in optimizing captive husbandry and breeding. In this review we
      discuss some of the mechanisms of ovarian control and the different tools being
      used to monitor female reproduction.

PMID- 29325880
TI  - Cryoprotective effect of glutamine, taurine, and proline on post-thaw semen
      quality and DNA integrity of donkey spermatozoa.
AB  - This study was conducted to evaluate the effect of amino acid addition to semen
      on post-thaw quality of donkey spermatozoa. Eighteen ejaculates were pooled and
      divided into aliquots which were cryopreserved in Gent A(r) containing 1%
      ethylene glycol (Gent-EG) and supplemented with 0 (as control), 20, 40, or 60 mM
      of glutamine, proline, or taurine. The greatest concentration (60 mM) of
      glutamine and taurine resulted in greater (P < 0.001) post-thaw sperm motility.
      Amino acid supplementation did not improve (P > 0.05) sperm morphology and
      membrane plasma integrity compared with the control samples. Whereas, improvement
      (P < 0.05) of acrosome integrity was observed with use of 60 mM glutamine. After
      thawing, there were no differences (P > 0.05) in the sperm DNA fragmentation
      index (sDFI) among treatments. The 60 mM glutamine and 40 mM taurine treatments,
      however, resulted in a reduction (P < 0.05) in sDFI values in the first 6 h of
      semen incubation, compared with the control samples. At 24 h, the sDFI values
      were less (P < 0.05) in all supplemented as compared with control samples, except
      for the 20 mM proline treatment group. In conclusion, supplementation of the Gent
      EG extender with glutamine or taurine at 60 mM improved post-thaw donkey sperm
      quality. The addition of proline to the freezing extender, however, did not
      provide any significant enhancement in sperm quality, compared with the control
      group.

PMID- 29325881
TI  - Rv2204c, Rv0753c and Rv0009 antigens specific T cell responses in latent and
      active TB - a flow cytometry-based analysis.
AB  - High global prevalence of latent TB infection (LTBI) is a key challenge in
      distinguishing patients with active pulmonary TB (PTB) from those with LTBI. The
      functional profile of CD4+ and CD8+ T cell cytokines produced as a response to
      Mycobacterium tuberculosis antigens vary during the course of tuberculosis (TB)
      infection. We evaluated antigen-specific CD4+ and CD8+ T cell cytokine response
      after overnight in vitro stimulation of peripheral blood with mycobacterial
      antigens ESAT-6, CFP-10, Rv2204c, Rv0753c and Rv0009 by flow cytometry. A
      significantly higher frequency of antigen-specific CD4+ or CD8+ IFN-gamma+ T
      cells were found in LTBI than in PTB. Among all the antigens used, Rv2204c
      specific CD8+ IFN-gamma+ displayed the positivity of 72% and 24% in LTBI and PTB
      respectively. In contrast to IFN-gamma, the frequencies of CD4+ or CD8+ secreting
      TNF-alpha+ cells were significantly high in PTB compared to LTBI. CD8+TNF-alpha+
      analysis showed 60% positivity in PTB and 13.6% positivity in LTBI against
      Rv0753c antigen stimulation. We also predicted Rv2204c specific CD8+ T cells
      secreting IL-10 or IL-4 showed maximum differentiation between LTBI and PTB. In
      conclusion, altered expression of Rv2204c-specific CD4+IFN-gamma+ and CD8+IL-4+ T
      cells in LTBI and PTB might be a useful biomarker to differentially diagnose LTBI
      and active TB.

PMID- 29325882
TI  - Pathophysiology of Escherichia coli pneumonia: Respective contribution of
      pathogenicity islands to virulence.
AB  - Ventilator-associated pneumonia (VAP) remains the most frequent life-threatening
      nosocomial infection. Enterobacteriaceae including Escherichia coli are
      increasingly involved. If a cumulative effect of pathogenicity islands (PAIs) has
      been shown for E. coli virulence in urinary tract or systemic infections, very
      little is known regarding pathophysiology of E. coli pneumonia. This study aimed
      to determine the role of each of the 7 PAIs present in pathogenic E. coli strain
      536 in pneumonia pathophysiology. We used mutant strains to screen
      pathophysiological role of PAI in a rat pneumonia model. We also test individual
      gene mutants within PAI identified to be involved in pneumonia pathogenesis.
      Finally, we determined the prevalence of these genes of interest in E. coli
      isolates from feces and airways of ventilated patients. Only PAIs I and III were
      significantly associated with rat pneumonia pathogenicity. Only the antigen-43
      (Ag43) gene in PAI III was significantly associated with bacterial pathogenicity.
      The prevalence of tested genes in fecal and airway isolates of ventilated
      patients did not differ between isolates. In contrast, genes encoding Ag43, the
      F17-fimbriae subunits, HmuR and SepA were more prevalent in VAP isolates with
      statistical significance for hmuR when compared to airway colonizing isolates.
      The E. coli PAIs involved in lung pathogenicity differed from those involved in
      urinary tract and bloodstream infections. Overall, extraintestinal E. coli
      virulence seems to rely on a combination of numerous virulence genes that have a
      cumulative effect depending on the infection site.

PMID- 29325884
TI  - Experimental Low Back Pain Decreased Trunk Muscle Activity in Currently
      Asymptomatic Recurrent Low Back Pain Patients During Step Tasks.
AB  - : Low back pain (LBP) patients show reorganized trunk muscle activity but if
      similar changes are manifest in recurrent LBP (R-LBP) patients during
      asymptomatic periods remains unknown. In 26 healthy and 27 currently asymptomatic
      R-LBP participants electromyographic activity (EMG) was recorded from trunk and
      gluteal muscles during series of stepping up and down on a step bench before and
      during experimentally intramuscular induced unilateral and bilateral LBP. Pain
      intensity was assessed using numeric rating scale (NRS) scores. Root mean square
      EMG (RMS-EMG) normalized to maximal voluntary contraction EMG and pain-evoked
      differences from baseline (DeltaRMS-EMG) were analyzed. Step task duration was
      calculated from foot sensors. R-LBP compared with controls showed higher baseline
      RMS-EMG and NRS scores of experimental pain (P < .05). In both groups, bilateral
      compared with unilateral experimental NRS scores were higher (P < .001) and
      patients compared with controls reported higher NRS scores during both pain
      conditions (P < .04). In patients, unilateral pain decreased DeltaRMS-EMG in the
      Iliocostalis muscle and bilateral pain decreased DeltaRMS-EMG in all back and
      gluteal muscles during step tasks (P < .05) compared with controls. In controls,
      bilateral versus unilateral experimental pain induced increased step task
      duration and trunk RMS-EMG whereas both pain conditions decreased step task
      duration and trunk RMS-EMG in R-LBP patients compared with controls (P < .05).
      PERSPECTIVE: Task duration and trunk muscle activity increased in controls and
      decreased in R-LBP patients during experimental muscle LBP. These results
      indicate protective strategies in controls during acute pain whereas R-LBP
      patients showed higher pain intensity and altered strategies that may be caused
      by the higher pain intensity, but the long-term consequence remains unknown.

PMID- 29325883
TI  - A Functional Neuroimaging Study of Expectancy Effects on Pain Response in
      Patients With Knee Osteoarthritis.
AB  - : Placebo treatments and healing rituals share much in common, such as the
      effects of expectancy, and have been used since the beginning of human history to
      treat pain. Previous mechanistic neuroimaging studies investigating the effects
      of expectancy on placebo analgesia have used young, healthy volunteers. Using
      functional magnetic resonance imaging (fMRI), we aimed to investigate the neural
      mechanisms by which expectancy evokes analgesia in older adults living with a
      chronic pain disorder and determine whether there are interactions with active
      treatment. In this fMRI study, we investigated the brain networks underlying
      expectancy in participants with chronic pain due to knee osteoarthritis (OA)
      after verum (genuine) and sham electroacupuncture treatment before and after
      experiencing calibrated experimental heat pain using a well tested expectancy
      manipulation model. We found that expectancy significantly and similarly
      modulates the pain experience in knee OA patients in both verum (n = 21, 11
      female; mean +/- SD age 57 +/- 7 years) and sham (n = 22, 15 female; mean +/- SD
      age 59 +/- 7 years) acupuncture treatment groups. However, there were different
      patterns of changes in fMRI indices of brain activity associated with verum and
      sham treatment modalities specifically in the lateral prefrontal cortex. We also
      found that continuous electroacupuncture in knee OA patients can evoke
      significant regional coherence decreases in pain associated brain regions. Our
      results suggest that expectancy modulates the experience of pain in knee OA
      patients but may work through different pathways depending on the treatment
      modality and, we speculate, on pathophysiological states of the participants.
      PERSPECTIVE: To investigate the neural mechanisms underlying pain modulation, we
      used an expectancy manipulation model and fMRI to study response to heat pain
      stimuli before and after verum or sham acupuncture treatment in chronic pain
      patients. Both relieve pain and each is each associated with a distinct pattern
      of brain activation.

PMID- 29325885
TI  - 9-Aminoacridine-based agents impair the bovine viral diarrhea virus (BVDV)
      replication targeting the RNA-dependent RNA polymerase (RdRp).
AB  - Bovine viral diarrhea virus (BVDV) infection is still a plague that causes
      important livestock pandemics. Despite the availability of vaccines against BVDV,
      and the implementation of massive eradication or control programs, this virus
      still constitutes a serious agronomic burden. Therefore, the alternative approach
      to combat Pestivirus infections, based on the development of antiviral agents
      that specifically inhibit the replication of these viruses, is of preeminent
      actuality and importance. Capitalizing from a long-standing experience in
      antiviral drug design and development, in this work we present and characterize a
      series of small molecules based on the 9-aminoacridine scaffold that exhibit
      potent anti-BVDV activity coupled with low cytotoxicity. The relevant viral
      protein target - the RNA-dependent RNA polymerase - the binding mode, and the
      mechanism of action of these new antivirals have been determined by a combination
      of in vitro (i.e., enzymatic inhibition, isothermal titration calorimetry and
      site-directed mutagenesis assays) and computational experiments. The overall
      results obtained confirm that these acridine-based derivatives are promising
      compounds in the treatment of BVDV infections and, based on the reported
      structure-activity relationship, can be selected as a starting point for the
      design of a new generation of improved, safe and selective anti-BVDV agents.

PMID- 29325886
TI  - Comparison analysis of orbital shape and volume in unilateral fractured orbits.
AB  - Facial fractures often result in changes of the orbital volume. These changes can
      be measured in three-dimensional (3D) computed tomography (CT) scans for
      preoperative planning and postoperative evaluation. The aim of this study was to
      analyze the orbital volume and shape before and after surgical treatment of
      unilateral orbital fractures using semi-automatic image segmentation and
      registration techniques. The orbital volume in 21 patients was assessed by a semi
      automatic model-based segmentation method. The fractured orbit was compared
      relative to the contralateral orbit. The same procedure was performed for the
      postoperative evaluation. Two observers performed the segmentation procedure, and
      the inter- and intraobserver variability was evaluated. The interobserver
      variability (mean volume difference +/- 1.96 SD) was -0.6 +/- 1.0 ml in the first
      trial and 0.7 +/- 0.8 ml in the second trial. The intra-observer variability was 
      0.2 +/- 0.7 ml for the first observer and 1.1 +/- 0.9 ml for the second observer.
      The average volume overlap (Dice similarity coefficient) between the fractured
      and contralateral side increased after surgery, while the mean and maximum
      surface distance decreased, indicating that the surgery contributed to a re
      establishment of size and shape. In conclusion, our study shows that the semi
      automatic segmentation method has precision for detecting volume differences down
      to 1.0 ml. The combination of semi-automatic segmentation and 3D shape analysis
      provides a powerful tool for planning and evaluating treatment of orbital
      fractures.

PMID- 29325887
TI  - Stiffness and strength of cranioplastic implant systems in comparison to cranial
      bone.
AB  - PURPOSE: The aim of this study was to evaluate skull replacement options after
      decompressive craniectomy by systematically investigating which combination of
      geometrical properties and material selection would result in a mechanical
      response comparable in stiffness to that of native skull bone and a strength as
      high or higher than the same. MATERIALS AND METHODS: The study was conducted
      using a Finite Element Model of the top part of a human skull. Native skull bone,
      autografts and commercial implants made of PEEK, solid titanium, two titanium
      meshes and a titanium-ceramic composite were modeled under a set load to evaluate
      deformation and maximum stress. RESULTS: The computational result showed a large
      variation of the strength and effective stiffness of the autografts and implants.
      The stiffness of native bone varied by a factor of 20 and the strength by a
      factor of eight. The implants span the entire span of the native skull, both in
      stiffness and strength. CONCLUSION: All the investigated implant materials had a
      potential for having the same effective stiffness as the native skull bone. All
      the materials also had the potential to be as strong as the native bone. To match
      inherent properties, the best choice of material and thickness is thus patient
      specific, depending on the quality of the patient's native bone.

PMID- 29325888
TI  - Computed exophthalmometry is an accurate and reproducible method for the
      measuring of eyeballs' protrusion.
AB  - PURPOSE: The aim of this study was to assess reproducibility of the repeated
      measurements from proposed computed exophthalmometry and to make a comparison
      with the Hertel exophthalmometer. METHODS: Computed tomography scans of patients
      with pathological (group 1) and intact orbits (group 2) were included in this
      retrospective study. In both groups, a single investigator measured a difference
      of eyeballs' protrusion using the proposed method of computed exophthalmometry.
      Briefly, the distances from the corneal apices of the left and right eyeballs to
      the line placed through the styloid processes of the temporal bones were measured
      and compared to each other three times independently. RESULTS: In some patients
      with intact lateral orbital rims the results of computed exophthalmometry
      correlated with the measurements from the Hetrel exophthalmometer. The analysis
      of the triple measurements with computed exophthalmometry revealed no significant
      difference in the value of standard deviation of the results in patients with
      intact and pathological orbits. In comparison with the Hertel-type
      exophthalmometry, the proposed method demonstrated very low variability and high
      repeatability of the measurements. The difference of 0.10-0.87 mm in the eyeballs
      protrusion should be considered as normal. Computed exophthalmometry is an
      accurate and reproducible method, which can be used for the measurements of
      eyeballs' protrusion.

PMID- 29325889
TI  - Early cell response of osteogenic cells on differently modified implant surfaces:
      Sequences of cell proliferation, adherence and differentiation.
AB  - OBJECTIVES: Osseointegration of dental implants is a crucial prerequisite for
      long-term survival. Therefore, surface modifications are needed to interact with
      the extracellular environment and to trigger osteogenic cell responses such as
      cell proliferation, adherence, and differentiation. The purpose of this study was
      to investigate different surface modifications in vitro over 2 weeks. MATERIALS
      AND METHODS: Commercially available cells from a human osteogenic cell line (HHOB
      c) were cultivated on the following surfaces: titanium with smooth surfaces
      (polished titanium (P), machined titanium (M), polyetheretherketone (Peek)),
      titanium with rough and hydrophilised surfaces (acid etched titanium (A),
      sandblasted acid etched titanium (SA and SA2), sandblasted acid etched
      hydrophilised (SAH), titanium plasma painted titanium (TPS)), titanium with
      calcium phosphate-containing surfaces (titanium plasma painted calcium phosphate
      modified titanium (TPS-CaP), sandblasted calcium phosphate modified titanium (S
      CaP), sandblasted acid etched calcium phosphate modified titanium (SA-CaP)), and
      zirconium-oxide (yttrium amplified zirconium (Z), yttrium amplified Ca2+
      delivering zirconium (Z-Ca)). Tissue culture polystyrene (TCPS) served as a
      control. Cell count was assessed after 24 h, 48 h, 72 h, 7 d, and 14 d;
      osteogenic cell adherence and differentiation were analysed by using cellular
      Quantitative Immuno-Cytochemistry (QIC) assay for alkaline phosphatase (AP),
      osteocalcin (OC), integrin alpha V (ITGAV), and talin (T). RESULTS: All tested
      surfaces showed a positive influence on the differentiation and adherence of
      osteogenic cells, especially P, M, A, TCPS, and Peek. After 48 h, the surfaces M,
      SA and SAH had induced a positive influence on adherence, whereas SA2, SA, and
      SAH triggered proliferation after 14 d. CONCLUSIONS: Rough and hydrophilised
      surface modifications, such as SAH, trigger osteogenic cell responses. These in
      vitro results highlight the potential use of SAH surface modifications of dental
      implants and indicate further clinical studies are warranted.

PMID- 29325890
TI  - Calorie Labels on the Restaurant Menu: Is the Use of Weight-Control Behaviors
      Related to Ordering Decisions?
AB  - BACKGROUND: There is emerging evidence that calorie information on restaurant
      menus does not similarly influence the ordering decisions of all population
      groups and may have unintended consequences for individuals who struggle with
      disordered eating or other weight-related concerns. OBJECTIVE: This study
      describes demographic patterns in the use of calorie information on restaurant
      menus and investigates relationships between using this information to limit
      calorie intake and measures of restaurant visit frequency and weight-related
      concerns and behavior. DESIGN/PARTICIPANTS: There were 788 men and 1042 women
      (mean age=31.0+/-1.6 years) who participated in the fourth wave of the Project
      EAT study. Participants were initially recruited from Minneapolis-St Paul, MN,
      schools and completed EAT-IV surveys online or by mail from 2015 to 2016. MAIN
      OUTCOME MEASURES: Participants self-reported weight-related concerns, restaurant
      eating, intuitive eating, dieting, healthy (eg, exercise) and unhealthy (eg, use
      of laxatives) weight-control behaviors, and binge eating. STATISTICAL ANALYSES
      PERFORMED: Descriptive statistics and linear and logistic regression models
      accounting for demographics and weight status. RESULTS: Approximately half of
      participants (52.7%) reported they had noticed calorie information while
      purchasing a meal or snack in a restaurant within the previous month. Among
      individuals who noticed calorie information, 38.2% reported they did not use it
      in deciding what to order. The most common use of calorie information was to
      avoid high-calorie menu items (50.1%) or to decide on a smaller portion (20.2%).
      Using menu labels to limit calories was related to binge eating among women and
      was associated with more weight-related concerns, dieting, and unhealthy weight
      control behaviors among both women and men. CONCLUSIONS: Nutrition educators and
      other health care professionals should talk with clients who struggle with
      disordered eating or weight-related concerns to learn about their use of calorie
      information at restaurants, address any potential unintended consequences, and
      promote healthy uses of calorie information.

PMID- 29325891
TI  - Fresh Fruit and Vegetable Program and Requests for Fruits and Vegetables Outside
      School Settings.
AB  - BACKGROUND: Consumption of fruits and vegetables (F/V) among elementary school
      aged children remains inadequate, especially among low-income children. The US
      Department of Agriculture's Fresh Fruit and Vegetable Program (FFVP) provides F/V
      as snacks to children during the school day, outside of school meals. School
      based initiatives are successful in changing behaviors in school settings;
      however, their influence on behaviors outside of schools needs investigation.
      OBJECTIVE: To examine whether FFVP participation is associated with F/V requests
      at stores, self-efficacy to ask for and choose F/V at home, and F/V consumption.
      DESIGN: Cross-sectional study. PARTICIPANT/SETTING: Fourth graders in six
      classrooms (n=296) from three urban, low-income school districts in Phoenix, AZ,
      were surveyed during 2015; one FFVP and one non-FFVP school from each district
      that were similar in school size, percent free/reduced-price meal eligibility,
      and race/ethnicity of enrolled students were selected. MAIN OUTCOME MEASURES:
      Children's self-reported F/V requests during shopping, their self-efficacy to ask
      for and choose F/V at home, and F/V consumption on the previous day (non-FFVP
      school day) were measured using questions adapted from validated surveys.
      STATISTICAL ANALYSIS: Multivariable mixed-effect regression models, adjusting for
      clustering of students within classes and classes within schools were explored.
      RESULTS: In models adjusting for individual-level factors (ie, age and sex) only,
      several significant positive associations were observed between school FFVP
      participation and healthier F/V outcomes. After additionally adjusting for school
      level factors (ie, total enrollment and % Hispanic/Latino students) significant
      associations were observed between school FFVP participation and more requests
      for vegetables during shopping (P<0.001), higher scores on self-efficacy to
      choose vegetables at home (P=0.004), stronger preferences for vegetables
      (P<0.001), and more frequent consumption of fruit (P=0.006). CONCLUSIONS: School
      FFVP participation was associated with more requests for vegetables during
      shopping and higher self-efficacy to make healthy choices at home, suggesting the
      influence of the FFVP may extend beyond the school day.

PMID- 29325892
TI  - Added Sugar Intake among Pregnant Women in the United States: National Health and
      Nutrition Examination Survey 2003-2012.
AB  - BACKGROUND: Despite associations of dietary added sugar with excess weight gain
      and chronic disease risk, intake among most Americans exceeds the recommended
      limits (<10% total energy). Maternal diet plays an important role in pregnancy
      related outcomes, but little is known about the extent of added sugar intake
      during pregnancy. OBJECTIVE: To assess intake and identify the top sources of
      added sugars in the diets of pregnant vs nonpregnant women in the United States.
      DESIGN: Cross-sectional analysis of data from the National Health and Nutrition
      Examination Survey (NHANES), 2003-2004 to 2011-2012. PARTICIPANTS: Four thousand
      one hundred seventy-nine pregnant and nonpregnant women (aged 20 to 39 years) who
      completed a dietary recall. STATISTICAL ANALYSES PERFORMED: Survey-weighted
      analyses were used to estimate means (95% CIs) in total grams and as percentage
      of total energy for added sugar intake by pregnancy status and by demographic
      subgroup and to identify leading sources of added sugar. RESULTS: Added sugar
      intake trended toward being higher in pregnant compared with nonpregnant women in
      absolute grams, 85.1 g (95% CI: 77.4 to 92.7) vs 76.7 g (95% CI: 73.6 to 79.9),
      respectively (P=0.06), but was lower among pregnant women when total energy
      intake was accounted for, 14.8% (95% CI: 13.8 to 15.7) vs 15.9% (95% CI: 15.2 to
      16.6) of total energy, respectively (P=0.03). Among pregnant women, added sugar
      intake was similar among demographic subgroups. However, in multivariable
      regression, pregnancy status significantly modified the associations of education
      and income with added sugar intake, whereby less educated and lower-income women
      who were pregnant had lower added sugar intakes compared with those who were not
      pregnant, but more educated or higher-income women did not exhibit this pattern.
      The top five sources of added sugar for all women were sugar-sweetened beverages;
      cakes, cookies, and pastries; sugars and sweets; juice drinks and smoothies; and
      milk-based desserts. CONCLUSIONS: Although pregnant women had higher energy
      intakes, this was not attributed to higher intakes of added sugar. Although
      education and income affected consumption during pregnancy, intake of added sugar
      among all women, regardless of pregnancy status, exceeded recommendations.

PMID- 29325893
TI  - WITHDRAWN: Stilamin inhibits intestinal and pancreatic injury in rats with severe
      acute pancreatitis by down-regulating LCN2 expression.
AB  - This article has been withdrawn at the request of the authors. 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- 29325894
TI  - Reference values for the creatine kinase response to professional Australian
      football match-play.
AB  - OBJECTIVES: Due to the importance of monitoring markers of muscle damage in high
      level sport from a medical and athlete recovery perspective, this study aimed to
      determine the upper limits of normal (ULN) for post-match plasma creatine kinase
      (CK) in professional Australian footballers. Raw CK values were considered, along
      with intra-individual deviations from the season-mean. DESIGN: Case series.
      METHODS: CK was collected between 36-48h following professional Australian
      football match-play. A total of 1565 samples from 62 players were assessed over
      three consecutive seasons. The ULN were determined for raw scores and as a
      percentage of each player's season-mean response. RESULTS: The ULN for raw CK, as
      determined by the 97.5th, 95th and 90th percentiles were 1715 (90%CI: 1605-1890),
      1380 (90%CI: 1325-1475) and 1110 (90%CI: 1050-1170) UL-1 respectively. The ULN
      intra-individual response (97.5th percentile) was defined as a player's score
      being greater than 94% (90%CI: 84-102%) above their season-mean. CONCLUSIONS:
      Professional Australian football elicits a profound effect on the CK response.
      The values provide a reference tool for athletes competing at this level of
      competition. The novel method of representing the CK response as a percentage
      difference from an individuals' season-mean enables a superior comparative
      ability between CK responses and reduces the high CK responder bias that occurs
      when using raw scores alone. The data will assist medical and conditioning staff
      in excluding medical emergencies and also aid in individualising the prescription
      of training loads and recovery to optimise athlete performance and minimise
      further muscle damage.

PMID- 29325895
TI  - The vertebrate limb: An evolving complex of self-organizing systems.
AB  - The paired appendages (fins or limbs) of jawed vertebrates contain an
      endoskeleton consisting of nodules, bars and, in some groups, plates of
      cartilage, or bone arising from replacement of cartilaginous templates. The
      generation of the endoskeletal elements occurs by processes involving production
      and diffusion of morphogens, with, variously, positive and negative feedback
      circuits, adhesion, and receptor dynamics with similarities to the mechanism for
      chemical pattern formation proposed by Alan Turing. This review presents a
      unified interpretation of the evolution and functioning of these mechanisms.
      Studies are described indicating that protocondensations, compacted mesenchymal
      cell aggregates that prefigure the appendicular skeleton, arise through the
      adhesive activity of galectin-1, a matricellular protein with skeletogenic
      homologs in all jawed vertebrates. In the cartilaginous and lobe-finned fishes
      (and to a variable extent in ray-finned fishes) it additionally cooperates with
      an isoform of galectin-8 to constitute a self-organizing network capable of
      generating arrays of preskeletal nodules, bars and plates. Further, in the
      tetrapods, a putative galectin-8 control module was acquired that may have
      enabled proximodistal increase in the number of protocondensations. In parallel
      to this, other self-organizing networks emerged that acted, via Bmp, Wnt, Sox9
      and Runx2, as well as transforming factor-beta and fibronectin, to convert
      protocondensations into skeletal tissues. The progressive appearance and
      integration of these skeletogenic networks over evolution occurred in the context
      of an independently evolved system of Hox protein and Shh gradients that
      interfaced with them to tune the spatial wavelengths and refine the identities of
      the resulting arrays of elements.

PMID- 29325896
TI  - Gut flora-dependent metabolite Trimethylamine-N-oxide accelerates endothelial
      cell senescence and vascular aging through oxidative stress.
AB  - Trimethylamine-N-oxide (TMAO), gut microbiota-dependent metabolites, has been
      shown to be associated with cardiovascular diseases. However, little is known
      about the relationship between TMAO and vascular aging. Here, we observed a
      change in TMAO during the aging process and the effects of TMAO on vascular aging
      and endothelial cell (EC) senescence. We analyzed age-related plasma levels of
      TMAO in young adults (18-44 years old), older adults (>= 65 years old), and 1
      month-old, 3-month-old, 6-month-old and 10-month-old senescence-accelerated mouse
      prone 8 (SAMP8) and age-matched senescence-accelerated mouse resistance 1 (SAMR1)
      models. We found that circulating TMAO increased with age both in humans and
      mice. Next, we observed that a TMAO treatment for 16 weeks induced vascular aging
      in SAMR1 mice and accelerated the process in SAMP8 mice, as measured by an
      upregulation of senescence markers including senescence-associated beta
      galactosidase (SA-beta-gal), p53, and p21, vascular dysfunction and remodeling.
      In vitro, we demonstrated that prolonged TMAO treatment induced senescence in
      human umbilical vein endothelial cells (HUVECs), characterized by reduced cell
      proliferation, increased expressions of senescence markers, stagnate G0/G1, and
      impaired cell migration. Furthermore, TMAO suppressed sirtuin 1 (SIRT1)
      expression and increased oxidative stress both in vivo and in vitro and then
      activated the p53/p21/Rb pathway resulting in increased p53, acetylation of p53,
      p21, and decreased CDK2, cyclinE1, and phosphorylation of Rb. In summary, these
      data suggest that elevated circulating TMAO during the aging process may
      deteriorate EC senescence and vascular aging, which is probably associated with
      repression of SIRT1 expression and increased oxidative stress, and, thus, the
      activation of the p53/p21/Rb pathway.

PMID- 29325897
TI  - An improved cell-permeable fluorogenic substrate as the basis for a highly
      sensitive test for NAD(P)H quinone oxidoreductase 1 (NQO1) in living cells.
AB  - NAD(P)H:quinone oxidoreductase 1 (NQO1) is a flavoenzyme upregulated in response
      to oxidative stress and in some cancers. Its upregulation by compounds has been
      used as an indicator of their potential anti-cancer properties. In this study we
      have designed, produced and tested a fluorogenic coumarin conjugate which
      selectively releases highly fluorescent 4-methylumbelliferone (4-MU) in the
      presence of NQO1. It was found that measuring 4-MU release rapidly and
      specifically quantitated NQO1 levels in vitro and in live cells. Both the
      substrate and its products freely perfused through cell membranes and were non
      toxic. The substrate was very specific with low background, and the assay itself
      could be done in less than 10minutes. This is the first assay to allow the
      quantitation of NQO1 in live cells which can then be retained for further
      experiments.

PMID- 29325898
TI  - Treatment of mantle cell lymphoma in older adults.
AB  - Mantle cell lymphoma (MCL) predominantly affects older adults, with a median age
      at diagnosis of 70years. A frequently aggressive yet incurable lymphoma, the goal
      of therapy for MCL is to turn a potentially life-threatening illness into a
      chronic disease with prolonged periods of remission. Large randomized trial data
      supports the standard treatment in younger patients of cytarabine-based induction
      followed by autologous stem cell transplant. Most patients will not be eligible
      for this intensive approach based on older age, comorbidities, and functional
      status, making the geriatric assessment an essential step in choosing the
      appropriate strategy. For these older patients, an increasing number of
      chemotherapy and non-chemotherapy based therapies are available that allow
      oncologists to better tailor treatment to the fitness of the patient. We will
      review treatment options for older patients with MCL in the first line and
      relapsed/refractory settings, highlighting the available evidence for providing
      longer progression-free intervals while also minimizing the adverse effects of
      unduly aggressive treatment.

PMID- 29325900
TI  - Orexin-B modulates synaptic transmission of rod bipolar cells in rat retina.
AB  - Orexin-A, -B play a crucial role in arousal and feeding by activating two G
      protein-coupled receptors: orexin receptor 1 (OX1R) and orexin receptor 2 (OX2R).
      Orexins, along with orexin receptors, are expressed in retinal neurons, and they
      have been shown to differentially modulate excitatory AMPA receptors of amacrine
      and ganglion cells in the inner retina. In this work we report that orexin-B
      modulates the activity of rod bipolar cells (RBCs) located in the outer retina of
      rat. Intravitreal injection of orexin-B increased the amplitude of the scotopic
      electroretinographic b-wave, a reflection of RBC activity, recorded in vivo.
      Patch clamp recordings in rat retinal slices showed that orexin-B did not change
      glutamatergic excitatory component of the RBC response driven by photoreceptors.
      Effects of orexin-B on GABA receptor-mediated synaptic transmission of RBCs were
      then examined. In retinal slice preparations orexin-B suppressed GABA receptor
      mediated inhibitory postsynaptic currents of RBCs in the inner plexiform layer.
      Furthermore, using whole-cell recordings in isolated RBCs it was shown that
      orexin-B suppressed GABAC receptor-, but not GABAA receptor-, mediated currents
      of the RBCs, an effect that was blocked by OX1R and OX2R antagonists. The orexin
      B-induced inhibition of GABAC currents was likely mediated by a Gi/o/PC-PLC/Ca2+
      independent PKC signaling pathway, as such inhibition was absent when each step
      of the above-pathway was blocked with GDP-beta-S/pertussis toxin (for Gi/o), D609
      (for PLC), bisindolylmaleimide IV (for PKC)/rottlerin (for PKCdelta),
      respectively. The orexin-B-induced potentiation of RBC activity may improve
      visual acuity and contrast sensitivity of the animal during the dark period (wake
      phase).

PMID- 29325899
TI  - Do ketone bodies mediate the anti-seizure effects of the ketogenic diet?
AB  - Although the mechanisms underlying the anti-seizure effects of the high-fat
      ketogenic diet (KD) remain unclear, a long-standing question has been whether
      ketone bodies (i.e., beta-hydroxybutyrate, acetoacetate and acetone), either
      alone or in combination, contribute mechanistically. The traditional belief has
      been that while ketone bodies reflect enhanced fatty acid oxidation and a general
      shift toward intermediary metabolism, they are not likely to be the key mediators
      of the KD's clinical effects, as blood levels of beta-hydroxybutyrate do not
      correlate consistently with improved seizure control. Against this unresolved
      backdrop, new data support ketone bodies as having anti-seizure actions.
      Specifically, beta-hydroxybutyrate has been shown to interact with multiple novel
      molecular targets such as histone deacetylases, hydroxycarboxylic acid receptors
      on immune cells, and the NLRP3 inflammasome. Clearly, as a diet-based therapy is
      expected to render a broad array of biochemical, molecular, and cellular changes,
      no single mechanism can explain how the KD works. Specific metabolic substrates
      or enzymes are only a few of many important factors influenced by the KD that can
      collectively influence brain hyperexcitability and hypersynchrony. This review
      summarizes recent novel experimental findings supporting the anti-seizure and
      neuroprotective properties of ketone bodies.

PMID- 29325901
TI  - Dynamic structure of lower limb joint angles during walking post-stroke.
AB  - BACKGROUND: Variability in joint kinematics is necessary for adaptability and
      response to everyday perturbations; however, intrinsic neuromotor changes
      secondary to stroke often cause abnormal movement patterns. How these abnormal
      movement patterns relate to joint kinematic variability and its influence on post
      stroke walking impairments is not well understood. OBJECTIVE: The purpose of this
      study was to evaluate the movement variability at the individual joint level in
      the paretic and non-paretic limbs of individuals post-stroke. METHODS: Seven
      individuals with hemiparesis post-stroke walked on a treadmill for two minutes at
      their self-selected speed and the average speed of the six-minute walk test while
      kinematics were recorded using motion-capture. Variability in hip, knee, and
      ankle flexion/extension angles during walking were quantified with the Lyapunov
      exponent (LyE). Interlimb differences were evaluated. RESULTS: The paretic side
      LyE was higher than the non-paretic side at both self-selected speed (Hip: 50%;
      Knee: 74%), and the average speed of the 6-min walk test (Hip: 15%; Knee: 93%).
      CONCLUSION: Differences in joint kinematic variability between limbs of persons
      post-stroke supports further study of the source of non-paretic limb deviations
      as well as the clinical implications of joint kinematic variability in persons
      post-stroke. The development of bilaterally-targeted post-stroke gait
      interventions to address variability in both limbs may promote improved outcomes.

PMID- 29325902
TI  - Which data should be tracked in forward-dynamic optimisation to best predict
      muscle forces in a pathological co-contraction case?
AB  - The choice of the cost-function for predicting muscle forces during a movement
      remains a challenge, especially in patients with neuromuscular disorders. Forward
      dynamics-based optimisations mainly track joint kinematics or torques, combined
      with a least-excitation criterion. Tracking marker trajectories and/or
      electromyography (EMG) has rarely been proposed. Our objective was to determine
      the best tracking objective-function to accurately predict the upper-limb muscle
      forces. A musculoskeletal model was created and EMG was simulated to obtain a
      reference movement - a shoulder abduction. A Gaussian noise (mean = 0; standard
      deviation = 15%) was added to the simulated EMG. Another noise - corresponding to
      the actual soft tissue artefacts (STA) of experimental shoulder abduction
      movements - was added to the trajectories of the markers placed on the model.
      Muscle forces were estimated from these noisy data, using forward dynamics
      assisted by six non-linear least-squared objective-functions. These functions
      involved the tracking of marker trajectories, joint angles or torques, with and
      without EMG-tracking. All six approaches used the same musculoskeletal model and
      were solved using a direct multiple shooting algorithm. Finally, the predicted
      joint angles, muscle forces and activations were compared to the reference
      values, using root-mean-square errors (RMSe) and biases. The force RMSe of the
      approach tracking both marker trajectories and EMG (18.45 +/- 12.60 N) was almost
      five times lower than the one of the approach tracking only joint angles (82.37
      +/- 66.26 N) or torques (85.10 +/- 116.40 N). Therefore, using EMG as a
      complementary tracking-data in forward dynamics seems to be promising for the
      estimation of muscle forces.

PMID- 29325903
TI  - GATA4 Loss-of-Function Mutation and the Congenitally Bicuspid Aortic Valve.
AB  - Aggregating evidence suggests that genetic determinants play a pivotal role in
      the pathogenesis of the congenitally bicuspid aortic valve (BAV). BAV is of
      pronounced genetic heterogeneity, and the genetic components underlying BAV in an
      overwhelming majority of patients remain elusive. In the current study, the whole
      coding exons and adjacent introns, as well as 5' and 3' untranslated regions of
      the GATA4 gene, which codes for a zinc-finger transcription factor crucial for
      the normal development of the aortic valve, were screened by direct sequencing in
      150 index patients with congenital BAV. The available family members of an
      identified mutation carrier and 300 unrelated, ethnically matched healthy
      individuals used as controls were also genotyped for GATA4. The functional effect
      of the mutation was characterized using a dual-luciferase reporter assay system.
      As a result, a novel heterozygous GATA4 mutation, p.E147X, was identified in a
      family with BAV transmitted in an autosomal dominant pattern. The nonsense
      mutation was absent in 600 control chromosomes. Functional deciphers revealed
      that the mutant GATA4 protein lost transcriptional activity compared with its
      wild-type counterpart. Furthermore, the mutation disrupted the synergistic
      transcriptional activation between GATA4 and NKX2.5, another transcription factor
      responsible for BAV. In conclusion, this study associates the GATA4 loss-of
      function mutation with enhanced susceptibility to a BAV, thus providing novel
      insight into the molecular mechanism underpinning the BAV.

PMID- 29325904
TI  - Impact of Complete Revascularization on Six-Year Clinical Outcomes and Incidence
      of Acute Decompensated Heart Failure in Patients With ST-Segment Elevation
      Myocardial Infarction and Multivessel Coronary Artery Disease.
AB  - It remains unclear whether complete revascularization (CR) reduces the incidences
      of acute decompensated heart failure (ADHF) and adverse cardiac outcomes in
      patients with ST-segment elevation myocardial infarction (STEMI) and multivessel
      coronary artery disease (MVD). A total of 453 hemodynamically stable patients
      with STEMI and MVD were retrospectively evaluated; the patients were divided into
      2 groups according to interventional strategy: CR (n = 240) and incomplete
      revascularization (IR) (n = 213). We analyzed the incidences of ADHF and major
      adverse cardiac events (MACE; a composite of all-cause mortality, myocardial
      infarction, and any revascularization) over a long follow-up period (median 6.3
      years). MACE developed in 158 patients (34.9%), and 40 patients (8.8%) were re
      admitted because of ADHF developing during follow-up. Results after propensity
      matching showed that CR did not reduce the incidence of ADHF (hazard ratio [HR]
      for IR 1.63, 95% confidence interval [CI] 0.63 to 4.22, p = 0.311). However, IR
      increased the risk of MACE (HR 1.73, 95% CI 1.09 to 2.74, p = 0.021),
      attributable principally to an increased risk of nontarget vessel
      revascularization (HR 3.12, 95% CI 1.23 to 7.92, p = 0.039). Although CR did not
      reduce the incidence of ADHF, CR might reduce repeat revascularization to treat
      non-infarct-related arteries in hemodynamically stable patients with STEMI and
      MVD.

PMID- 29325905
TI  - Infiltrating macrophages are broadly activated at the early stage to support
      acute skeletal muscle injury repair.
AB  - Acute skeletal muscle injury repair requires an adequate inflammatory response
      predominated by macrophage infiltration. We studied the activation of
      infiltrating macrophages by analyzing the expression of M1/M2 signature genes.
      Most of the intramuscular macrophages were Ly6Chi at day 1 after BaCl2 injection,
      while many were Ly6Clo at day 3. Ly6Chi macrophages at day 1 expressed a high
      level of both M1 and M2 genes, and the Ly6Chi and Ly6Clo macrophages at day 3
      expressed a similar level of many M1/M2 genes. Infiltrating macrophages are
      broadly activated rather than polarized at the early stage to support acute
      skeletal muscle injury repair.

PMID- 29325906
TI  - Immune-related miRNA expression patterns in peripheral blood mononuclear cells
      differ in multiple sclerosis relapse and remission.
AB  - MiRNAs were shown to participate in development of autoimmune inflammatory
      process in multiple sclerosis (MS). To investigate miRNAs involvement in relapse
      remission MS course, we analyzed expression of immune-related miRNAs in PBMC of
      treatment-naive relapsing and remitting MS patients and healthy controls. The
      upregulation of miR-126-3p, miR-146b-5p, miR-155, miR-196a-5p, miR-21-5p, miR-223
      3p, miR-326 and miR-379-5p in remission compared to relapse was observed; when
      apply gender stratification, miR-223-3p and miR-379-5p were upregulated only in
      men. Therefore, miRNAs play essential role in maintaining stable MS course and
      this process has certain gender-specific differences.

PMID- 29325907
TI  - Corrigendum to 'Cannabinoid CB1 receptor inverse agonist MJ08 stimulates glucose
      production via hepatic sympathetic innervation in rats': European Journal of
      Pharmacology 814 (2017) 232-239.

PMID- 29325908
TI  - Corrigendum to ' Rosuvastatin inhibits pressure-induced fibrotic responses via
      the expression regulation of prostacyclin and prostaglandin E 2 in rat renal
      tubular cells.': [European Journal of Pharmacology 700 (2013) 65-73].

PMID- 29325909
TI  - Corrigendum to Trans-4-methoxy-beta-nitrostyrene relaxes rat thoracic aorta
      through a sGC-dependent pathway: European Journal of Pharmacology 807 (2017) 182
      189.

PMID- 29325910
TI  - Corrigendum to Additional effect of metformin and celecoxib against lipid
      dysregulation and adipose tissue inflammation in high-fat fed rats with insulin
      resistance and fatty liver: [Eur.J.Pharmacol.789(2016)60-67].

PMID- 29325911
TI  - Corrigendum to: "Preventive and therapeutic effects of caffeic acid against
      inflammatory injury in striatum of MPTP-treated mice":
      [Eur.J.Pharmacol.670(2011)441-447].

PMID- 29325912
TI  - Impact of Childhood Vaccine Discussion Format Over Time on Immunization Status.
AB  - OBJECTIVE: Presumptive formats to initiate childhood vaccine discussions (eg,
      "Well, we have to do some shots") have been associated with increased vaccine
      acceptance after one visit compared to participatory formats (eg, "How do you
      feel about vaccines?"). We characterize discussion format patterns over time and
      the impact of their repeated use on vaccine acceptance. METHODS: We conducted a
      longitudinal prospective cohort study of children of vaccine-hesitant parents
      enrolled in a Seattle-based integrated health system. After the child's 2-, 4-,
      and 6-month visits, parents reported the format their child's provider used to
      begin the vaccine discussion (presumptive, participatory, or other). Our outcome
      was the percentage of days underimmunized of the child at 8 months old for 6
      recommended vaccines. We used linear regression and generalized estimating
      equations to test the association of discussion format and immunization status.
      RESULTS: We enrolled 73 parent-child dyads and obtained data from 82%, 73%, and
      53% after the 2-, 4-, and 6-month visits, respectively. Overall, 65% of parents
      received presumptive formats at >=1 visit and 42% received participatory formats
      at >=1 visit. Parental receipt of presumptive formats at 1 and >=2 visits (vs no
      receipt) was associated with significantly less underimmunization of the child,
      while receipt of participatory formats at >=2 visits was associated with
      significantly more underimmunization. Visit-specific use of participatory (vs
      presumptive) formats was associated with a child being 10.1% (95% confidence
      interval, 0.3, 19.8; P = .04) more days underimmunized (amounting to, on average,
      98 more days underimmunized for all 6 vaccines combined). CONCLUSIONS:
      Presumptive (vs participatory) discussion formats are associated with increased
      immunization.

PMID- 29325913
TI  - Efficacy of a Web-Based Oral Case Presentation Instruction Module: Multicenter
      Randomized Controlled Trial.
AB  - OBJECTIVE: Effective self-directed educational tools are invaluable. Our
      objective was to determine whether a self-directed, web-based oral case
      presentation module would improve medical students' oral case presentations
      compared to usual curriculum, and with similar efficacy as structured oral
      presentation faculty feedback sessions. METHODS: We conducted a pragmatic
      multicenter cluster randomized controlled trial among medical students rotating
      in pediatric clerkships at 7 US medical schools. In the clerkship's first 14
      days, subjects were instructed to complete an online Computer-Assisted Learning
      in Pediatrics Program (CLIPP) oral case presentation module, an in-person faculty
      led case presentation feedback session, or neither (control). At the clerkship's
      end, evaluators blinded to intervention status rated the quality of students'
      oral case presentations on a 10-point scale. We conducted intention-to-treat
      multivariable analyses clustered on clerkship block. RESULTS: Study participants
      included 256 CLIPP (32.5%), 263 feedback (33.3%), and 270 control (34.2%)
      subjects. Only 51.1% of CLIPP subjects completed the assigned presentation
      module, while 98.5% of feedback subjects participated in presentation feedback
      sessions. Compared to controls, oral presentation quality was significantly
      higher in the feedback group (adjusted difference in mean quality, 0.28; 95%
      confidence interval, 0.08, 0.49) and trended toward being significantly higher in
      the CLIPP group (0.19; 95% confidence interval, -0.006, 0.38). The quality of
      presentations in the CLIPP and feedback groups was not significantly different (
      0.10; 95% confidence interval, -0.31, 0.11). CONCLUSIONS: The quality of oral
      case presentations delivered by students randomized to complete the CLIPP module
      did not differ from faculty-led presentation feedback sessions and was not
      statistically superior to control.

PMID- 29325914
TI  - Micro-cultural customization of organ donation propagation messages.
AB  - OBJECTIVE: Organ transplantation is plagued by limited availability of organs.
      This study investigated the effect of messages promoting organ donation which
      were customized according to the language-defined micro-cultures in Switzerland.
      METHODS: Community-, informative-, and emotional-oriented messages were carried
      by conventional flyers. A 3 * 3 between-subjects experiment was conducted with
      short- and long-term willingness to donate, long-term signing of organ donation
      card and long-term interpersonal communication on organ donation as outcome
      variables. RESULTS: The culturally customized interventions appeared to have no
      immediate effect and consequently no differential effect on willingness to donate
      organs and on signing a donor card. Among the Swiss Germans, of the three
      messages, the community-oriented one instigated less interpersonal communication.
      CONCLUSION: Findings are consistent with a mechanism in which the message does
      not have an immediate effect on willingness to donate organs but motivates
      further thought and related behaviors that lead to higher commitment and later
      increased willingness to donate. PRACTICE IMPLICATIONS: Targeting not only the
      message but also the objective that drives the messages must be considered.
      Campaigns should include elements that build on the unfolding commitment process
      to promote the follow-up actions that lead to greater willingness.

PMID- 29325915
TI  - In vivo nonspecific immunomodulatory and antispasmodic effects of common purslane
      (Portulaca oleracea Linn.) leaf extracts in ICR mice.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Portulaca oleracea (common purslane) is used in
      traditional medicine to cure various illnesses. However, its immune-protective
      properties and antispasmodic effects still need more pharmacological data if the
      plant will be utilized in herbal and drug formulations. Therefore, the present
      study determined the capacity of this plant species to modulate nonspecific
      immune responses and to confirm its antispasmodic activity in vivo in ICR mice.
      MATERIALS AND METHODS: Phagocytic activity of peritoneal macrophage, splenic
      lymphocyte proliferation and plasma lysozyme levels were measured in mice that
      were immunosuppressed using cyclophosphamide and treated with the ethyl acetate
      extract of Portulaca oleracea. In addition, the charcoal meal transit test was
      used to measure intestinal motility using ethanolic (EtOH), hexane (HEX), and
      ethyl acetate (EA) solvent extracts. Phytochemical analysis was undertaken and
      DPPH scavenging properties of the three solvent extracts were also determined.
      RESULTS: The EA extract of P. oleracea exhibited immunoactivity through
      significant increase in phagocytosis and higher proliferative response in splenic
      lymphocytes. Plasma lysozyme level was also higher in EA-treated mice at high
      dose but this was not statistically significant. Decreased intestinal motility
      was also exhibited in mice treated with the three leaf solvent extracts compared
      to the negative control and the acetylcholine-treated group. The antispasmodic
      activity of the solvent extracts was comparable to that of the atropine-treated
      group. Phytochemical analysis showed the presence of tannins in EA extract in
      addition to alkaloids and steroids. The EtOH and HEX extracts contain alkaloids,
      steroids and terpenoids. DPPH scavenging activity was highest in the EA extract.
      CONCLUSIONS: The present study showed that the EA extract of P. oleracea leaves
      ameliorated the immunosuppressive action of cyclophosphamide in mice. The results
      also indicated that the three solvent extracts of the plant decreased smooth
      muscle spasms in mice ileum. However, further experiments are warranted to
      further isolate the plant's immunoactive component. Also, the mechanisms involved
      in the immunoactivity and antispasmodic properties of P. oleracea deserve full
      elucidation.

PMID- 29325916
TI  - Proanthocyanidin polymeric tannins from Stryphnodendron adstringens are effective
      against Candida spp. isolates and for vaginal candidiasis treatment.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The stem bark of Stryphnodendron adstringens
      (Mart.) Coville is popularly used as anti-inflammatory, astringent and in the
      treatment of wounds and vaginal infections. Several pharmacological activities
      have been scientifically proven by in vitro and in vivo experimental assays for
      antibacterial, antiviral, antiprotozoan, anti-inflammatory and antioxidant. AIM
      OF THE STUDY: We investigated whether proanthocyanidin polymeric tannins from the
      Stryphnodendron adstringens stem bark with antifungal activity against Candida
      albicans in vitro are also active against planktonic and biofilm cells of Candida
      non-albicans (CNA, including fluconazole-resistant isolates) and are capable of
      controlling Candida vaginitis in vivo. MATERIALS AND METHODS: A total of 46
      clinical isolates and 5 reference Candida spp. strains were used in this study.
      The antifungal effects in vitro of tannins (F2 and sub-fraction F2.4) from S.
      adstringens stem bark were evaluated using a broth microdilution assay (for
      planktonic yeasts and biofilm dispersion cells) or by XTT assay (for biofilm
      sessile cells). For in vivo antifungal activity analysis, mice with vaginal
      infection by C. albicans or C. glabrata were treated with a topical gel
      containing F2 (alone or combined with oral fluconazole), and the vaginal
      histopathology and fungal burden (by CFU counts from vaginal homogenates) were
      analyzed. RESULTS: F2 and F2.4 inhibited the proliferation of planktonic cells of
      Candida spp., especially that of fluconazole- and/or amphotericin B-resistant
      isolates. F2 and F2.4 also inhibited the proliferation of Candida biofilm
      dispersion cells. Moreover, a gel containing F2 efficiently controlled vaginal
      infection by C. albicans and C. glabrata in mice, with no noticeable toxicity to
      vaginal tissue. CONCLUSIONS: Our data show that proanthocyanidin polymeric
      tannins obtained from S. adstringens have antifungal activity in vitro against C.
      albicans and CNA (including fluconazole-resistant isolates) and presented
      efficacy in the control of candidiasis in murine model. Therefore, these tannins
      have potential use in the treatment of vaginal candidiasis, representing
      interesting alternatives to current antifungals.

PMID- 29325917
TI  - Increase in insulin sensitivity by the association of chicoric acid and
      chlorogenic acid contained in a natural chicoric acid extract (NCRAE) of chicory
      (Cichorium intybus L.) for an antidiabetic effect.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Chicory (Cichorium intybus L.) is an indigenous
      vegetable widely cultivated in Europe, America and Asia. In ancient times, the
      leaves, flowers, seeds, and roots have been used as a wealth of health benefits
      including its tonic effects, the ability to ease digestive problems and to
      detoxify liver. In Indian traditional therapy, chicory was known to possess
      antidiabetic effect. In the traditional medicine of Bulgaria and Italy, chicory
      was used as hypoglycemic decoctions. AIMS OF THE STUDIES: We wanted to obtain the
      complete chemical composition of the natural chicoric acid extract (NCRAE), a
      chicory root extract rich in chicoric acid, which previously showed its glucose
      tolerance effect in normal rats. To investigate if the whole NCRAE is required to
      be effective, we performed a comparative in vivo experiment on STZ diabetic rats
      treated either with NCRAE or a mixture composed of the two major compounds of
      NCRAE. MATERIALS AND METHODS: LC-MS method has been used to analyze the
      exhaustive composition of NCRAE: we have determined that chicoric acid and
      chlorogenic acid represented 83.8% of NCRAE. So, we have prepared a solution
      mixture of chicoric acid and chlorogenic acid named SCCAM, in order to compare in
      vivo the antidiabetic effects of this last and NCRAE in streptozotocin diabetic
      rats. In vitro experiments were performed on L6 cell line both for glucose uptake
      and for the protective effect against H2O2 oxidative stress. Also, we have
      evaluated DPPH and ORAC (Oxygen Radical Absorbance Capacity) antioxidative
      capacities of the two compositions. RESULTS: The LC-MS analysis confirmed the
      high abundance of chicoric acid (64.2%) in NCRAE and a second part of NCRAE is
      composed of caffeoylquinic acids (CQAs) at 19.6% with among them the chlorogenic
      acid. This result has permitted us to prepare a mixture of synthetic L-chicoric
      acid (70%) and synthetic chlorogenic acid (30%): the solution is designated
      SCCAM. Our results showed that both NCRAE and SCCAM are able to improve a glucose
      tolerance in STZ diabetic rats after a subchronic administration of seven days.
      Alone NCRAE allows to significantly decrease the basal hyperglycemia after six
      days of treatment. To explain these difference of effects between NCRAE and
      SCCAM, we have compared their in vitro effects on the L6 muscle cell line both
      for the insulin sensitizing effect and for their protective action in
      pretreatment against H2O2. We have also compared their antioxidant capacities. In
      conclusion, we demonstrated that NCRAE, a natural extract of chicory (Cichorium
      intybus) rich in CRA and CQAs improves glucose tolerance and reduces the basal
      hyperglycemia in STZ diabetic rats.

PMID- 29325919
TI  - Patients with Cerebral Stroke Have an Increased Risk of Gastroesophageal Reflux
      Disease: A Population-Based Cohort Study.
AB  - BACKGROUND: Medical complications following stroke often result in significant
      morbidity. This study was designed to investigate the prevalence and risk of
      gastroesophageal reflux disease (GERD) between patients with stroke and those
      without stroke in Taiwan. METHODS AND RESULTS: This retrospective cohort study
      was conducted using the Taiwan National Health Insurance Research Database. The
      study included 18,412 patients newly diagnosed as having stroke during 2000-2006
      and 18,412 patients without stroke frequency-matched by sex, age, and index year.
      All patients were followed from the index date to December 31, 2011. The Cox
      proportional hazards regression model was used to estimate the GERD risk. The
      GERD risk was approximately 1.51-times higher in the stroke group than in the
      nonstroke group, after adjustment for age, sex, and the cumulative incidence of
      some comorbidities. GERD was positively associated with stroke; the male sex
      (adjusted hazard ratio [HR] = 1.31); an age of 65 years or older (adjusted HR =
      1.11); hyperlipidemia (adjusted HR = 1.14); ischemic heart disease (adjusted HR =
      1.27); renal disease (adjusted HR = 1.45); and use of aspirin (adjusted HR =
      2.34), clopidogrel (adjusted HR = 1.41), and dipyridamole (adjusted HR = 1.30).
      CONCLUSIONS: This study indicates a significantly higher GERD risk in patients
      with stroke than in the nonstroke group. In clinical practice, neurologists
      should focus on the risk of GERD symptoms.

PMID- 29325918
TI  - Bioactive fraction of Rhodiola algida against chronic hypoxia-induced pulmonary
      arterial hypertension and its anti-proliferation mechanism in rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Rhodiola algida var. tangutica (Maxim.) S.H. Fu
      is a perennial plant of the Crassulaceae family that grows in the mountainous
      regions of Asia. The rhizome and roots of this plant have been long used as
      Tibetan folk medicine for preventing high latitude sickness. AIM OF THE STUDY:
      The aim of this study was to determine the effect of bioactive fraction from R.
      algida (ACRT) on chronic hypoxia-induced pulmonary arterial hypertension (HPAH)
      and to understand the possible mechanism of its pharmacodynamic actions.
      MATERIALS AND METHODS: Male Sprague-Dawley rats were separated into five groups:
      control group, hypoxia group, and hypoxia+ACRT groups (62.5, 125, and
      250mg/kg/day of ACRT). The chronic hypoxic environment was created in a hypobaric
      chamber by adjusting the inner pressure and oxygen content for 4 weeks. After 4
      weeks, major physiological parameters of pulmonary arterial hypertension such as
      mPAP, right ventricle index (RV/LV+S, RVHI), hematocrit (Hct) levels and the
      medial vessel thickness (wt%) were measured. Protein and mRNA expression levels
      of proliferating cell nuclear antigen (PCNA), cyclin D1, p27Kip1 and cyclin
      dependent kinase 4 (CDK4)) were detected by western blotting and real time PCR
      respectively. Chemical profile of ACRT was revealed by ultra performance liquid
      chromatography coupled with quadrupole time of flight mass spectrometry (UHPLC-Q
      TOF-MS/MS). RESULTS: The results showed that a successful HPAH rat model was
      established in a hypobaric chamber for 4 weeks, as indicated by the significant
      increase in mPAP, RV/LV+S, RV/BW and wt%. Compared with the normal group,
      administration of ACRT reduced mPAP, right ventricular hypertrophy, pulmonary
      small artery wall thickness, and damage in ultrastructure induced by hypoxia in
      rats. PCNA, cyclin D1, and CDK4 expression was reduced (p<0.05), and p27Kip1
      expression increased (p<0.05) in hypoxia+ACRT groups compared to hypoxia. 38
      constituents in bioactive fraction were identified by UHPLC-Q-TOF-MS/MS.
      CONCLUSION: Our results suggest that ACRT could alleviate chronic hypoxia-induced
      pulmonary arterial hypertension. And its anti-proliferation mechanism in rats
      based on decreasing PCNA, cyclin D1, CDK4 expression level and inhibiting p27Kip1
      degradation.

PMID- 29325920
TI  - Twenty-Four Syndrome: An Untold Presentation of Pontine Hemorrhage.
AB  - Pontine hemorrhages are relatively uncommon. Various atypical manifestations of
      pontine stroke like eight-and-a-half syndrome, fifteen-and-a-half syndrome, and
      sixteen syndrome have been described in the past. We came across a case of
      pontine bleed that presented with bilateral facial palsy, bilateral horizontal
      gaze palsy, and contralateral sensorineural hearing loss accounting to the
      hitherto not described "twenty-four syndrome" with Horner's syndrome and left
      hemiparesis.

PMID- 29325922
TI  - The Cost-Effectiveness of Using PARO, a Therapeutic Robotic Seal, to Reduce
      Agitation and Medication Use in Dementia: Findings from a Cluster-Randomized
      Controlled Trial.
AB  - OBJECTIVES: To examine the within-trial costs and cost-effectiveness of using
      PARO, compared with a plush toy and usual care, for reducing agitation and
      medication use in people with dementia in long-term care. DESIGN: An economic
      evaluation, nested within a cluster-randomized controlled trial. SETTING: Twenty
      eight facilities in South-East Queensland, Australia. PARTICIPANTS: A total of
      415 residents, all aged 60 years or older, with documented diagnoses of dementia.
      INTERVENTION: Facilities were randomized to 1 of 3 groups: PARO (individual,
      nonfacilitated 15-minute sessions, 3 afternoons per week for 10 weeks); plush toy
      (as per PARO but with artificial intelligence disabled); and usual care.
      MEASUREMENTS: The incremental cost per Cohen-Mansfield Agitation Inventory-Short
      Form (CMAI-SF) point averted from a provider's perspective. Australian New
      Zealand Clinical Trials Registry (BLINDED FOR REVIEW). RESULTS: For the within
      trial costs, the PARO group was $50.47 more expensive per resident compared with
      usual care, whereas the plush toy group was $37.26 more expensive than usual
      care. There were no statistically significant between-group differences in
      agitation levels after the 10-week intervention. The point estimates of the
      incremental cost-effectiveness ratios were $13.01 for PARO and $12.85 for plush
      toy per CMAI-SF point averted relative to usual care. CONCLUSION: The plush toy
      used in this study offered marginally greater value for money than PARO in
      improving agitation. However, these costs are much lower than values estimated
      for psychosocial group activities and sensory interventions, suggesting that both
      a plush toy and the PARO are cost-effective psychosocial treatment options for
      agitation.

PMID- 29325923
TI  - Ethical and Practical Ways in Which MOELI (Medical Orders for End-of-Life
      Intervention) Advance the Physician Orders for Life-Sustaining Treatment (POLST)
      Program.

PMID- 29325921
TI  - Energy Flux: The Link between Multitrophic Biodiversity and Ecosystem
      Functioning.
AB  - Relating biodiversity to ecosystem functioning in natural communities has become
      a paramount challenge as links between trophic complexity and multiple ecosystem
      functions become increasingly apparent. Yet, there is still no generalised
      approach to address such complexity in biodiversity-ecosystem functioning (BEF)
      studies. Energy flux dynamics in ecological networks provide the theoretical
      underpinning of multitrophic BEF relationships. Accordingly, we propose the
      quantification of energy fluxes in food webs as a powerful, universal tool for
      understanding ecosystem functioning in multitrophic systems spanning different
      ecological scales. Although the concept of energy flux in food webs is not novel,
      its application to BEF research remains virtually untapped, providing a framework
      to foster new discoveries into the determinants of ecosystem functioning in
      complex systems.

PMID- 29325924
TI  - Prediction of the Hydrogen Peroxide-Induced Methionine Oxidation Propensity in
      Monoclonal Antibodies.
AB  - Methionine oxidation in therapeutic antibodies can impact the product's
      stability, clinical efficacy, and safety and hence it is desirable to address the
      methionine oxidation liability during antibody discovery and development phase.
      Although the current experimental approaches can identify the oxidation-labile
      methionine residues, their application is limited mostly to the development
      phase. We demonstrate an in silico method that can be used to predict oxidation
      labile residues based solely on the antibody sequence and structure information.
      Since antibody sequence information is available in the discovery phase, the in
      silico method can be applied very early on to identify the oxidation-labile
      methionine residues and subsequently address the oxidation liability. We believe
      that the in silico method for methionine oxidation liability assessment can aid
      in antibody discovery and development phase to address the liability in a more
      rational way.

PMID- 29325925
TI  - Microfluidic Approaches for the Characterization of Therapeutic Proteins.
AB  - In the last decades, the pharmaceutical market has experienced an increase in the
      number of therapeutic proteins. The high activity and selectivity of these
      macromolecules is often achieved at the expense of complex structures, which
      exhibit several biophysical properties that must be carefully controlled and
      optimized for the successful development of these drugs as well as for
      guaranteeing their quality and safety. This need has motivated the application of
      a variety of biophysical techniques to analyze properties of therapeutic proteins
      and protein solutions including interactions, aggregation, solubility, viscosity,
      and thermal stability. After briefly summarizing currently available experimental
      approaches, we highlight the emerging possibilities offered by advances in
      microfluidic technology for the analysis of therapeutic proteins during
      manufacturing and formulation.

PMID- 29325926
TI  - The study of the inhibitory effect of calcium oxalate monohydrate's
      crystallization by two medicinal and aromatic plants: Ammi visnaga and Punica
      granatum.
AB  - INTRODUCTION: Urinary lithiasis is a recurrent disease defined by the presence of
      calculi in the urinary tract. Most urinary calculi have as a major component
      calcium oxalate which occurs mainly in two crystalline forms: Calcium oxalate
      monohydrate (whewellite) and calcium oxalate dihydrate (weddellite). The target
      behind, this work is to study the inhibiting effect of the calcium oxalate's
      crystallization by the extract of the Ammi visnaga and the Punica granatum.
      METHODS: The inhibition of crystallization has been studied in vitro with both
      the absence and the presence of the different concentrations of the extracts of
      the two plants. This study consists in measurement, with the UV-Visible
      spectrophotometer, the temporal evolution of the optical density at lambda equal
      to 620nm corresponding to the formation of the crystals due to the mixing of
      metastable solutions of calcium and oxalate. The characterization of the crystals
      is carried out in parallel by both the Fourier transform infrared spectra (FT-IR)
      and the observation of the crystals with the help of an optical microscope. In
      this respect, the inhibition percentages were calculated from the turbidity
      slopes in the presence and absence of the extract. RESULTS: The results obtained
      were more effective, especially for Punica granatum with percentages of 97.8+/
      0.12 and 83.46+/-1.34% against nucleation and aggregation, respectively, the
      order of Ammi visnaga was as follow: 73.25+/-0.81 and 59.44+/-3.3%. Thus, all
      correlation coefficients are greater than 0.95 and all coefficients of variation
      are less than 10%. CONCLUSIONS: The prevention and treatment of urinary lithiasis
      and especially in the case of recurrence by plants remains an alternative choice
      for medical methods. This study justified the efficacy of the plants Ammi visnaga
      and in particular Punica granatum against the crystallization of calcium oxalate.
      LEVEL OF EVIDENCE: 3.

PMID- 29325927
TI  - Health care access and quality for persons with disability: Patient and provider
      recommendations.
AB  - BACKGROUND: Significant disparities in health care access and quality persist
      between persons with disabilities (PWD) and persons without disabilities (PWOD).
      Little research has examined recommendations of patients and providers to improve
      health care for PWD. OBJECTIVE: We sought to explore patient and health care
      provider recommendations to improve health care access and quality for PWD
      through focus groups in the physical world in a community center and in the
      virtual world in an online community. METHODS: In all, 17 PWD, 4 PWOD, and 6
      health care providers participated in 1 of 5 focus groups. Focus groups were
      conducted in the virtual world in Second Life(r) with Virtual Ability, an online
      community, and in the physical world at Agape Community Center in Milwaukee, WI.
      Focus group data were analyzed using a grounded theory methodology. RESULTS:
      Themes that emerged in focus groups among PWD and PWOD as well as health care
      providers to improve health care access and quality for PWD were: promoting
      advocacy, increasing awareness and knowledge, improving communication, addressing
      assumptions, as well as modifying and creating policy. Many participants
      discussed political empowerment and engagement as central to health care reform.
      CONCLUSIONS: Both PWD and PWOD as well as health care providers identified common
      themes potentially important for improving health care for PWD. Patient and
      health care provider recommendations highlight a need for modification of current
      paradigms, practices, and approaches to improve the quality of health care
      provision for PWD. Participants emphasized the need for greater advocacy and
      political engagement.

PMID- 29325929
TI  - Post-Stroke Cognitive Impairment, Depression and Apathy: Untangling the
      Relationship.

PMID- 29325928
TI  - Limonoids and triterpenoid from fruit of Swietenia macrophylla.
AB  - Five new limonoids, swieteliacates A-E (1-5) and a tirucallane-type triterpenoid,
      swietesenin (6), together with four known compounds (7-10) were isolated from
      fruit of Swietenia macrophylla. Their structures were determined by spectroscopic
      analyses. The new compounds were tested in vitro for their cytotoxic effects
      against five human cancer cell lines. Compound 2 exhibited moderate cytotoxic
      activities against SW480 and HL-60 cancer cell lines with IC50 values of 30.6 and
      32.9MUM, respectively.

PMID- 29325931
TI  - Corrigendum to "Dose-related ethanol intake, Cx43 and Nav1.5 remodeling:
      Exploring insights of altered ventricular conduction and QRS fragmentation in
      excessive alcohol users" [J. Mol. Cell. Cardiol. 114 (2018) 150-160].

PMID- 29325930
TI  - Integrated study on comparative transcriptome and skeletal muscle function in
      aged rats.
AB  - The present study aimed to reveal aging-related changes in the skeletal muscle of
      SD rats by comparing transcriptome analysis, integrated with muscle physiological
      parameters. Ten rats aged 25 months were set as the old group (OG) and ten rats
      aged 6 months were set as the young group (YG). After 6 weeks of feeding, the
      body mass, grip strength, and gastrocnemius muscle mass were determined, and the
      differentially expressed genes were analyzed by transcriptome sequencing,
      followed by GO enrichment analysis and KEGG analysis. The results showed that the
      muscle index and the relative grip strength were lower in OG rats than YG rats.
      The expressions of AMPK, UCP3, IGF-1, several ion channel associated genes and
      collagen family genes were down-regulated in OG rats. MGMT, one of the strength
      determining genes and CHRNa1, a subunit of the acetylcholine receptor were up
      regulated in OG rats. The present results supply the global transcriptomic
      information involved in aging related skeletal muscle dysfunction in rats. The
      reduced expressions of AMPK, IGF-1, and CASK can explain the losses of muscle
      mass and function in the aged rats. In addition, the up-regulation of MGMT and
      CHRNa1 also contribute to muscle wasting and weakness during aging.

PMID- 29325932
TI  - Riboflavin attenuates myocardial injury via LSD1-mediated crosstalk between
      phospholipid metabolism and histone methylation in mice with experimental
      myocardial infarction.
AB  - The underlying mechanisms responsible for the cardioprotective effects of
      riboflavin remain elusive. Current study tested the hypothesis that riboflavin
      protects injured myocardium via epigenetic modification of LSD1. Here we showed
      that myocardial injury was attenuated and cardiac function was improved in
      riboflavin-treated mice with experimental myocardial infarction (MI), while these
      protective effects of riboflavin could be partly blocked by cotreatment with LSD1
      inhibitor. Riboflavin also reduced apoptosis in hypoxic (1% oxygen) H9C2 cell
      lines. Results of ChIP-seq for H9C2 cells showed that riboflavin activated LSD1,
      as verified by decreased H3K4me2 levels of target genes. Subsequent LEGO
      bioinformatics analysis indicated that phospholipid metabolism genes Lpcat2 and
      Pld1 served as the potential target genes responsible for the LSD1 mediated
      protective effects. Overexpressions of Lpcat2 and Pld1 aggravated hypoxic injury
      in H9C2 cells, while these detrimental effects could be attenuated by
      overexpression of LSD1. We thus propose that riboflavin alleviates myocardial
      hypoxic/ischemic injury by activating LSD1 cellular activity and modulating the
      expression of phospholipid metabolism genes. LSD1-mediated crosstalk between
      phospholipid metabolism and histone methylation might thus be an important
      mechanism for the cardioprotective effects of riboflavin.

PMID- 29325933
TI  - Sestrin2 prevents age-related intolerance to post myocardial infarction via
      AMPK/PGC-1alpha pathway.
AB  - We have revealed that a novel stress-inducible protein, Sestrin2, declines in the
      heart with aging. Moreover, there is an interaction between Sestrin2 and energy
      sensor AMPK in the heart in response to ischemic stress. The objective of this
      study is to determine whether Sestrin2-AMPK complex modulates PGC-1alpha in the
      heart and protects the heart from ischemic insults. In order to characterize the
      role of cardiac Sestrin2-AMPK signaling cascade in aging, C57BL/6 wild type young
      mice (3-4months), aged mice (24-26months) and young Sestrin2 KO mice were
      subjected to left anterior descending coronary artery occlusion for in vivo
      regional ischemia. Intriguingly, ischemic AMPK activation was blunted in aged WT
      and young Sesn2 KO hearts as compared with young WT hearts. In addition, the AMPK
      downstream PGC-1alpha was down-regulated in the aged and Sestrin2 KO hearts
      during post myocardial infarction. To further determine the regulation of AMPK on
      mitochondrial functions in aging, the downstream of mitochondrial biogenesis PGC
      1alpha transcriptional factor were measured. The results demonstrated that the
      PGC-1alpha downstream effectors TFAM and UCP2 were impaired in the aged and
      Sestrin2 KO post-MI hearts as compared to the young hearts. While the apoptotic
      flux markers such as AIF, Bax/Bcl-2 were up-regulated in both aged and Sestrin2
      KO hearts versus young hearts. Furthermore, both Sestrin2 KO and aged hearts
      demonstrated more susceptible to ischemic insults as compared to young hearts.
      Additionally, the adeno-associated virus (AAV9)-Sestrin2 delivered to the aged
      hearts via a coronary delivery approach significantly rescued the ischemic
      tolerance of aged hearts. Taken together, the decreased Sestrin2 levels in aging
      lead to an impaired AMPK/PGC-1alpha signaling cascade and an increased
      sensitivity to ischemic insults.

PMID- 29325934
TI  - Direct perception vs inferential processes in reading an opponent's mind: The
      case of a goalkeeper facing a soccer penalty kick: Comment on "Seeing mental
      states: An experimental strategy for measuring the observability of other minds"
      by Cristina Becchio et al.

PMID- 29325935
TI  - Upgrading Gestalt psychology with variational neuroethology: The case of
      perceptual pleasures: Comment on "Answering Schrodinger's question: A free-energy
      formulation" by M.J. Desormeau Ramstead et al.

PMID- 29325936
TI  - Carotid Atherosclerotic Plaque Features in Patients with Acute Ischemic Stroke.
AB  - OBJECTIVE: To investigate the carotid atherosclerotic plaque features in patients
      with acute ischemic stroke. METHODS: A total of 288 patients meeting the included
      criteria were enrolled and divided into an ulcerated plaque group (n = 139) and a
      nonulcerated plaque group (n = 149). Patients in the ulcerated plaque group were
      further subdivided into <50% and >=50% stenosis groups. Carotid plaque component
      characteristics including luminal stenosis, carotid plaque volume, hypoechoic
      plaque volume, and hyperechoic plaque volume were analyzed by color Doppler
      ultrasound measurement. Associations between ulcerated plaque and carotid plaque
      features were also evaluated. The relationships among the levels of MMP-9, hs
      CRP, and carotid stenosis rate were detected by enzyme-linked immunosorbent
      assay. RESULTS: The plaque volume, hypoechoic plaque volume, and luminal stenosis
      in the ulcerated plaque group were higher than that of the nonulcerated plaque
      group (P < 0.05). Ulcerated plaque was positively associated with luminal
      stenosis, plaque volume, and hypoechoic plaque volume after adjusting for sex and
      age. The result remained similar after adjusting for age, sex, and carotid
      luminal stenosis. The levels of MMP-9 and hs-CRP in the ulcerated plaque group
      were significantly higher than those of the nonulcerated plaque group (P < 0.01).
      For the ulcerated plaque group, the higher the carotid stenosis rate, the higher
      the level of MMP-9 and hs-CRP. CONCLUSIONS: Higher carotid atherosclerosis plaque
      volume, hypoechoic plaque volume, and luminal carotid stenosis may be symptoms of
      ulcerated plaque. Increased MMP-9 and hs-CRP levels could be used as adjunctive
      therapies of carotid stenosis at the molecular level.

PMID- 29325937
TI  - Histopathologic Analysis of Tamoxifen on Epidural Fibrosis.
AB  - BACKGROUND: Epidural fibrosis is a challenging topic in spinal surgery. This
      phenomenon constitutes one of the main reasons behind postlaminectomy syndrome or
      failed back surgery syndrome, which leads to persistent back and leg pain in
      association with compression and/or stretching the nerve root or the dura. The
      exact mechanism of action in epidural fibrosis is complex and remains uncertain.
      Excessive deposition of collagen, fibronectin, and dermatan sulfate, known as the
      "extracellular matrix," and decrease of tissue cellularity results in epidural
      fibrosis. The most investigated and important actor in epidural fibrosis as well
      as in other forms of aberrant wound healing is presumed to be transforming growth
      factor-1beta formation. Tamoxifen (TAM), a synthetic nonsteroidal antiestrogen
      used in breast cancer, is also effective in inhibiting fibroblast proliferation
      via downregulation of transforming growth factor-1beta. METHODS: Twenty-four
      adult male rats were randomly divided into 3 groups. Laminectomy was the sole
      intervention in the control group. Spongostan was placed in the operation lodge
      after laminectomy in the second group. In the treatment group, TAM was
      administrated orally after laminectomy. Epidural fibrosis, dural thickness,
      inflammatory response, and arachnoidal involvement were evaluated and graded
      histopathologically. RESULTS: Epidural fibrosis, dural thickness, and
      inflammatory response in the subjects treated with TAM were significantly less
      than in the control and Spongostan group and the differences were statistically
      significant. Although arachnoidal involvement was observed in a subject in the
      TAM group, the differences between all groups weren't statistically significant.
      CONCLUSIONS: Tamoxifen reduced epidural fibrosis, dural thickness, and
      inflammatory response after laminectomy in rats.

PMID- 29325938
TI  - Coarctation of the Aorta Complicated with Intracranial Aneurysm: A Case Report
      and Literature Review.
AB  - BACKGROUND: Coarctation of the aorta (CoA) complicated with rupture and
      hemorrhage of intracranial aneurysms is not commonly seen in clinical practice.
      Here we report a middle-aged female patient who presented with acute severe
      headache. CASE DESCRIPTION: Head computed tomography (CT) demonstrated an
      extensive subarachnoid hemorrhage. Digital subtraction angiography demonstrated
      coarctation and occlusion of the proximal thoracic aorta and occlusion of the
      terminal aortic arch. Aortic-intracranial CT angiography (CTA) confirmed a CoA
      complicated with an anterior communicating artery aneurysm. Clipping of the
      anterior communicating artery aneurysm was performed via a left lateral orbital
      approach. Postoperative intracranial CTA showed complete clipping of the
      aneurysm. The patient was discharged postoperatively with good recovery.
      CONCLUSIONS: The pathophysiological mechanism of CoA complicated with
      intracranial aneurysm remains unclear, but attention should be given to the
      relationship between the 2 entities in clinical practice, and effective treatment
      should be provided according to specific conditions.

PMID- 29325939
TI  - Liponeurocytoma of the Cerebellopontine Angle.
AB  - BACKGROUND: Liponeurocytoma is a very rare tumor classified as grade II (neuronal
      and mixed neuronal-glial tumors) according to 2016 World Health Organization
      classification of tumors of the central nervous system. The median age at
      detection is 50 years, and the most frequent location is the posterior cranial
      fossa, especially within the cerebellar hemispheres; liponeurocytomas arising in
      the cerebellopontine angle (CPA) are exceptional. CASE DESCRIPTION: Here we
      report the clinical, radiological, and pathological characteristics of a CPA
      liponeurocytoma in a 35-year-old woman, as well as a review of the literature.
      This unusual cisternal location raises the issue of the differential imaging
      diagnosis with much more common CPA tumors (e.g., meningiomas, vestibular
      schwannomas, ependymomas, epidermoid cyst, hemangioblastomas, medulloblastomas).
      CONCLUSION: To the best of our knowledge, 59 cases of cerebellar liponeurocytomas
      have been reported to date, which include only 6 cases of CPA liponeurocytomas.
      Treatment relies on total removal whenever possible, with an excellent prognosis,
      but a high MIB-1 index (>10%) and/or incomplete tumor resection are the main
      adverse prognostic factors.

PMID- 29325940
TI  - Clinical Features, Treatment, and Prognostic Factors of 56 Intracranial and
      Intraspinal Clear Cell Meningiomas.
AB  - OBJECTIVE: Intracranial and intraspinal clear cell meningiomas (CCMs) are rarely
      reported because of their extremely low incidence, and the current understanding
      of CCM is poor. The purpose of this study was to analyze the incidence and the
      clinical, radiologic, pathologic, and prognostic features of intracranial and
      intraspinal CCMs. METHODS: Among 14,310 cases of intracranial and intraspinal
      meningiomas that were surgically treated between 2006 and 2016 at Beijing Tian
      Tan Hospital, 56 were chosen for analysis and retrospectively reviewed. To
      determine which parameters were associated with longer progression-free survival
      (PFS) and overall survival (OS), statistical analysis was performed. RESULTS:
      CCMs accounted for approximately 0.39% of all intracranial and intraspinal
      meningiomas. Patients with CCM had a mean age of 32.3 years and there was a
      female predilection (20 males and 36 females). Gross total resection was achieved
      in 35 cases, and subtotal resection was achieved in 21 cases. All patients were
      followed up for 10-206 months after surgery. Twenty-six patients experienced
      tumor recurrence, and the median PFS was 48.0 months. The 1-year, 3-year, and 5
      year PFS was 87.5%, 59.8%, and 41.8%, respectively. Twelve patients died of tumor
      recurrence, and the median OS was not available. The 1-year, 3-year, and 5-year
      OS was 98.2%, 91.3%, and 65.8%, respectively. Univariate analysis showed that
      total tumor removal was significantly associated with a better prognosis.
      Multivariate analysis confirmed only Simpson grade III and IV resection as an
      independent risk factor for shorter PFS. Radiotherapy mildly improved PFS after
      both gross total resection and subtotal resection, showing no significant
      difference because of the small sample size and short follow-up duration.
      CONCLUSIONS: CCM is a rare subtype of World Health Organization grade II
      meningioma. CCM typically involves young patients and shows a female predilection
      and high recurrence rate. When possible, total resection is the primary and most
      suitable treatment for CCM. For patients with primary tumors, radiotherapy is
      recommended after the initial operation regardless of the extent of resection.
      For patients with disease recurrence, secondary surgery combined with
      radiotherapy might serve as an effective treatment.

PMID- 29325942
TI  - Perineural Spread of Melanoma to the Brachial Plexus: Identifying the Anatomic
      Pathway(s).
AB  - BACKGROUND: Perineural spread of melanoma is a well-known mechanism of metastasis
      in cases involving cranial nerves. Brachial plexus involvement is rare, and the
      pathway is unknown. METHODS: A retrospective review of the Mayo Clinic database
      was performed to identify patients with a history of melanoma and brachial plexus
      compromise treated between 1994 and 2017. Inclusion criteria were a history of
      melanoma, a clinical diagnosis of brachial plexopathy, radiologic features
      consistent with perineural spread, and biopsy of melanoma within nerves. RESULTS:
      We identified 42 patients (24 men and 18 women; median age, 61 years; range, 37
      84 years) with a history of melanoma and brachial plexopathy. On a review of
      clinical information, 2 cases met our inclusion criteria. Both patients presented
      with progressive brachial plexopathy, and imaging studies revealed features
      consistent with perineural spread. In 40 excluded patients, brachial plexopathy
      was caused by metastasis to axillary lymph nodes (n = 11), trauma (n = 8), post
      surgical sequelae (n = 7), tumors other than melanoma (n = 5), inflammation (n =
      5), radiation (n = 2), a combination of radiation and postsurgical changes (n =
      1), and radiculopathy (n = 1). CONCLUSIONS: The 2 patients identified had similar
      clinical and radiologic features. We believe that there is a pattern of
      perineural spread to the brachial plexus through the cervical plexus. A
      literature review identified several recently published cases demonstrating an
      analogous mechanism of melanoma spread involving upper cervical nerves,
      supporting our proposed pathway.

PMID- 29325941
TI  - Toward Shorter Hospitalization After Endoscopic Transsphenoidal Pituitary
      Surgery: Day-by-Day Analysis of Early Postoperative Complications and
      Interventions.
AB  - BACKGROUND: It is unclear which patients have the greatest risk of developing
      complications in the first days after endoscopic transsphenoidal pituitary
      surgery (ETS) and how long patients should stay hospitalized after surgery. The
      objective of this study is to identify which patients are at risk for early
      postoperative medical and surgical reinterventions to optimize the length of
      hospitalization. METHODS: The medical records of 146 patients who underwent ETS
      for a pituitary adenoma between January 2013 and July 2016 were reviewed
      retrospectively. Data were collected on baseline patient-related characteristics,
      characteristics of the pituitary adenoma, perioperative complications and
      interventions, and postoperative outcomes. Patients who underwent additional
      interventions on days 2, 3, and 4 after ETS were identified as cases, and
      patients who did not have any interventions after day 1 postoperatively were
      identified as controls. RESULTS: Diabetes mellitus (odds ratio [OR], 4.279; 95%
      confidence interval [CI], 1.149-15.933; P = 0.03), incomplete adenoma resection
      (OR, 2.840; 95% CI, 1.228-6.568; P = 0.02) and increased morning sodium
      concentration on day 2 after surgery (OR, 5.211; 95% CI, 2.158-12.579; P <0.001)
      were associated with reinterventions. Patients without interventions on day 1 or
      2 had only an 18.6% chance of a reintervention (OR, 0.201; 95% CI, 0.095-0.424).
      CONCLUSIONS: Patients with diabetes mellitus, incomplete adenoma resection, and
      increased morning sodium concentration on day 2 after surgery have an increased
      chance on reinterventions. In addition, patients without any interventions on day
      1 and 2 are at low risk for later reinterventions. These patients could be
      suitable candidates for early hospital discharge.

PMID- 29325943
TI  - Neurosurgical Care: Availability and Access in Low-Income and Middle-Income
      Countries.
AB  - BACKGROUND: An estimated 5 billion people worldwide lack access to basic surgical
      care. In particular, the vast majority of low-income and middle-income countries
      (LMICs) currently struggle to provide adequate neurosurgical services.
      Significant barriers exist, including limited access to trained medical, nursing,
      and allied health staff; lack of equipment; and availability of services at
      reasonable distance and at reasonable cost to patients. An accurate assessment of
      current neurosurgical capacity in LIMCs is an essential first step in tackling
      this deficit. OBJECTIVE: To quantify the neurosurgical operational capacity and
      assess access to neurosurgical services in LMICs, by taking into account the
      location of workforce and services. METHODS: A total of 141 LMICs were contacted
      and asked to report the number of currently practicing neurosurgeons, access to
      computed tomographic and magnetic resonance imaging, and availability of
      neurosurgical equipment (microscope, endoscope, bipolar diathermy, high-speed
      neurosurgical drill). A proposed World Federation of Neurosurgeons classification
      was used to stratify cities based on the level of neurosurgical care that could
      be provided. The data were geocoded and analyzed in Redivis (Redivis Inc.) to
      assess the percentage of the population covered within a 2-hour travel time of a
      city offering differing levels of neurosurgical care. RESULTS: 68 countries
      provided complete data (response rate, 48.2%). Eleven countries reported having
      no practicing neurosurgeons. The average percentage of the population with access
      to neurosurgical services within a 2-hour window is 25.26% in sub-Saharan Africa,
      62.3% in Latin America and the Caribbean, 29.64% in East Asia and the Pacific,
      52.83% in South Asia, 79.65% in the Middle East and North Africa, and 93.3% in
      Eastern Europe and Central Asia. CONCLUSIONS: There are several challenges to the
      provision of adequate neurosurgical services in low-resource settings. This study
      used mapping techniques to determine the current global neurosurgical workforce
      capacity and distribution. We have used our findings to identify areas for
      improvement. These include increasing and improving neurosurgical training
      programs worldwide, recruiting students and young physicians into the field, and
      retaining existing neurosurgeons within their home countries.

PMID- 29325944
TI  - Hemorrhagic Cavernous Sinus Hemangioma with Sudden-Onset Abducens Palsy.
AB  - BACKGROUND: We report a rare case of hemorrhagic cavernous sinus hemangioma with
      sudden onset of abducens palsy. CASE DESCRIPTIONS: Sudden onset of diplopia
      occurred in a 49-year-old female. Head computed tomography findings revealed a
      high-density mass in the right cavernous sinus with protrusion to the sphenoid
      sinus. Endoscopic endonasal surgery was performed, though early recurrence was
      noted. A Gamma Knife surgical procedure was then performed to prevent early
      recurrence after histopathologic confirmation of cavernous sinus hemangioma.
      Thereafter, the tumor was controlled and abducens palsy disappeared. CONCLUSIONS:
      For treatment of cavernous sinus hemangioma, stereotactic radiosurgery should be
      considered as primary or adjuvant treatment in the very early phase after
      removal, to avoid early recurrence.

PMID- 29325945
TI  - Impact of Right-Sided Aneurysm, Rupture Status, and Size of Aneurysm on
      Perforator Infarction Following Microsurgical Clipping of Posterior Communicating
      Artery Aneurysms with a Distal Transsylvian Approach.
AB  - BACKGROUND: Posterior communicating artery (PCoA) aneurysms are among the most
      common aneurysms. Because blockage of the PCoA and perforators can cause adverse
      outcomes, occlusion of these arteries by surgical clipping should be avoided. The
      impact of factors on PCoA perforator infarction when using a distal transsylvian
      approach for PCoA aneurysms was examined. METHODS: A total of 183 patients
      underwent PCoA aneurysm clipping, excluding application of fenestrated clips.
      Patients were divided into 2 groups: patients with PCoA perforator infarction
      (infarction group) and patients without infarction (noninfarction group).
      Multiple factors were analyzed in the 2 groups. RESULTS: Twenty-two of the 183
      patients (12.0%) showed perforator infarction, mainly on magnetic resonance
      imaging evaluation, resulting in permanent deficits in 2 patients (1.1%). The
      proportion of right-sided operations (86.4% vs. 53.4%; P = 0.005) and surgery for
      rupture (90.9% vs. 55.9%; P = 0.002) were significantly higher in the infarction
      group than in the noninfarction group. Aneurysms were significantly larger in the
      infarction group (8.4 +/- 3.8 mm) than in the noninfarction group (6.3 +/- 3.0
      mm; P = 0.02). Ruptured status (odds ratio [OR], 7.35; P = 0.01), right side (OR,
      5.19; P = 0.01), and aneurysm size (OR, 1.18; P = 0.02) remained independent
      predictors of perforator infarction on multivariate logistic regression analysis.
      CONCLUSIONS: Ruptured status, right side, and large PCoA aneurysm were
      independent predictors of PCoA perforator infarction. Symptoms due to PCoA
      perforating infarction were mostly transient and rarely affected outcomes.

PMID- 29325946
TI  - Skip Hemilaminectomy for Large, Multilevel Spinal Epidural Hematomas: Report of a
      Series of 11 Patients.
AB  - OBJECTIVE: We present our experience with a modification of the conventional
      techniques for the removal of large spinal epidural hematomas (SEHs), based on
      multilevel "skip hemilaminectomies." METHODS: Eleven patients with SEHs extending
      over 5 or more spinal segments were treated at our institution via a modified
      hemilaminectomy technique from 2008 to 2014. This procedure, that we called "skip
      hemilaminectomy," consists in performing consecutive, alternating, unilateral
      laminar decompressions at 2-3 levels, followed by sublaminar undercutting, ipsi-
      and contralateral flavectomy, plus hematoma removal. RESULTS: Complete clot
      evacuation and full neurologic recovery were always achieved. A short hospital
      stay, fast postoperative mobilization, a minimized need of analgesic drugs, and
      no complications were recorded. CONCLUSIONS: In our preliminary experience, skip
      hemilaminectomy seems to be as safe as more conventional techniques (laminectomy,
      extended hemilaminectomy) for the removal of large multilevel SEHs, granting full
      neurologic improvement, short surgical times-even for very large lesions-and no
      complications at follow-up.

PMID- 29325947
TI  - Usefulness of Oblique Coronal Computed Tomography and Magnetic Resonance Imaging
      in the Endoscopic Endonasal Approach to Treat Skull Base Lesions.
AB  - OBJECTIVE: This report examines the usefulness of the preoperative image to
      orient the surgeon in the sphenoid sinus during endoscopic endonasal
      transsphenoidal surgery (ETSS). METHODS: ETSS was performed in 100 cases of
      sellar lesion and used to classify the sphenoid sinus septum shape. Preoperative
      computed tomography and magnetic resonance imaging were performed for 2 types of
      coronal imaging: conventional and oblique. Expected sphenoid sinus septum shape
      was compared with those from ETSS to estimate concordance. The confirmation rate
      of anatomic landmarks in the sphenoid sinus by endoscopic observation was
      compared in various types of septum and the identification rate in oblique
      coronal imaging was also examined. RESULTS: The most common septum shape was
      single type (31%), followed by branched (26%), parallel (18%), none (12%), cross
      (9%), and bridge (4%) types. In oblique coronal images, preoperative evaluation
      and endoscopic findings were consistent in 93%-100% of cases. However, with
      conventional coronal images, the concordance rate was 22.2%-83.9%, and in the
      none, branched, and cross types, the concordance rate was significantly lower
      than that for oblique coronal images. Although confirmation of the midline
      through estimation of landmarks by endoscopic observation was difficult in 33
      cases, preoperative computed tomography and magnetic resonance imaging showed
      landmarks in all cases and oblique coronal images best indicated the midline.
      CONCLUSIONS: Use of oblique coronal images in addition to conventional images
      provided good orientation of anatomic structures in the sphenoid sinus. The
      combination of preoperative imaging and endoscopic observation could allow safer
      surgery in ETSS.

PMID- 29325948
TI  - Spinal Metastasis Resulting from Atypical Thymic Carcinoid: A Case Report.
AB  - BACKGROUND: Thymic carcinoid with spinal metastasis is an extremely rare entity.
      Clinically, the tumor presents either by its endocrine manifestations or by
      mechanical compression of surrounding structures. However, no previously
      published case studies have reported neck pain and neurologic deficit in the
      initial presentation of an atypical thymic carcinoid. CASE DESCRIPTION: A 56-year
      old man, a nonsmoker, presented with a 12-month history of intermittent neck pain
      and a 1-month history of progressive numbness and weakness of the right upper
      limb. Cervical MRI showed multiple abnormal signals and C2 soft-tissue mass
      intruding into the vertebral canal. Cervical CT scan showed multiple bone
      lesions. The diagnosis of thymic carcinoid was obtained by preoperative lymph
      node biopsy. The patient underwent cervical laminectomy and occipitocervical
      fixation. Significant alleviation of pain and neurologic improvement were
      achieved. The postoperative pathological examination confirmed the diagnosis of
      thymic carcinoid. CONCLUSIONS: Neck pain and neurologic deficit could be the
      first presentation of thymic carcinoid with spinal metastasis. Palliative surgery
      is an effective method to improve quality of life in patients with thymic
      carcinoid with spinal metastasis.

PMID- 29325949
TI  - Comparison of MED and PELD in the Treatment of Adolescent Lumbar Disc Herniation:
      A 5-Year Retrospective Follow-Up.
AB  - OBJECTIVE: To compare the efficacy and safety of minimally endoscopic discectomy
      (MED) and percutaneous endoscopic lumbar discectomy (PELD) in the treatment of
      adolescent lumbar disc herniation (ALDH). METHODS: We retrospectively collected
      data from 30 patients with ALDH who underwent MED and 48 patients with ALDH who
      underwent PELD at our hospital between January 2010 and January 2012. Baseline
      data included age, sex, symptom duration, and surgical segment. Perioperative
      data included duration of surgery duration, blood loss, and duration of
      postoperative hospitalization. The Oswestry Disability Index (ODI) and visual
      analog scale (VAS) for both the lower back and leg were recorded as surgical
      outcomes. All surgical outcomes were recorded before surgery, at 1 week after
      surgery, at 6 months after surgery, and at final follow-up. RESULTS: There were
      no significant differences in baseline data between the MED and PELD groups. Both
      groups showed improvements in ODI and VAS scores before surgery and at the final
      follow-up time point (P < 0.05); however, the MED group had a higher mean ODI
      score at 1 week (12.44 +/- 6.39 vs. 7.25 +/- 6.40; P = 0.02) and 6 months (9.33
      +/- 7.43 vs. 3.97 +/- 7.64; P = 0.04) after surgery. In addition, mean VAS scores
      for lower back pain were higher in the MED group at 1 week (1.93 +/- 1.39 vs.
      0.91 +/- 0.85; P = 0.01), 6 months (1.80 +/- 1.15 vs. 0.61 +/- 0.94; P = 0.00),
      and final follow-up (1.87 +/- 1.46 vs. 0.65 +/- 0.88; P = 0.00), as was mean VAS
      score for radicular pain at 1 week after surgery (1.48 +/- 0.76 vs. 0.74 +/-
      0.81; P = 0.01). One patient in each group experienced recurrent lumbar disc
      herniation. No other complications were reported in either group. CONCLUSIONS:
      Both PELD and MED are effective and safe surgical techniques for the treatment of
      ALDH; however, compared with MED, PELD is more advantageous for lower back pain
      and provides more rapid resolution of radicular pain.

PMID- 29325950
TI  - A Novel Technique for Cervical Laminoplasty Fusion: Simultaneously Enhancing
      Stabilization and Decompression in Various Cervical Myelopathies: A Technical
      Note and Outcomes.
AB  - BACKGROUND: Cervical laminectomy has 2 major disadvantages: postlaminectomy
      adhesion of dural membrane and lack of a fusion bed. The objective of this study
      was to determine whether simultaneous cervical laminoplasty with fusion (CLPF)
      might overcome these unwanted outcomes. METHODS: Patients who underwent CLPF for
      treating cervical myelopathy with instability who were followed up for at least
      12 months were enrolled. Preoperative and postoperative Neck Disability Index
      (NDI) and Japanese Orthopedic Association (JOA) scores before and after surgery,
      recovery rates (RRs), C2-C7 lordosis, and fusion success rates were evaluated.
      RESULTS: The study cohort comprised 50 patients (35 males and 15 females; mean
      age, 60.5 +/- 14.0 years) who underwent CLPF. The average duration of clinical
      follow-up was 24.6 +/- 16.1 months. Mean preoperative and postoperative NDI
      scores were 27.0 +/- 10.6 and 17.6 +/- 7.2, respectively (P = 0.004). Mean
      preoperative and postoperative JOA scores were 10.4 +/- 4.2 and 13.6 +/- 3.0,
      respectively (P = 0.001). The mean JOA RR was 49.8 +/- 42.2%. No significant
      changes in C2-7 lordosis were noted after surgery (preoperative, 7.0 +/- 8.0
      degrees ; postoperative, 7.3 +/- 6.3 degrees ; P = 0.789). The fusion success
      rate was 96% (48 of 50 patients). Fusion mass areas at C5 level were
      significantly different between the opening side and the hinge side (opening
      side, 15.8 +/- 13.1 mm2; hinge side, 50.8 +/- 27.2 mm2; P < 0.001). There was no
      postoperative restenosis or epidural fibrosis. CONCLUSIONS: CLPF might be useful
      for canal decompression and a good fusion bed while avoiding postoperative
      epidural fibrosis.

PMID- 29325951
TI  - Shunt Nephritis: An Increasingly Unfamiliar Diagnosis.
AB  - BACKGROUND: Shunt nephritis is a rare, reversible immune-complex mediated
      complication of cerebrospinal fluid (CSF) shunt infection that can progress to
      end-stage renal disease and even death if diagnosis is delayed. CASE DESCRIPTION:
      The present case report details the manifestation and clinical course of shunt
      nephritis in a 50-year-old patient who presented with symptoms of nephrotic
      syndrome 30 years after ventriculojugular shunt placement. Diagnosis was delayed
      due to initial negative CSF and blood cultures, but a later CSF culture was
      positive for Propionibacterium acnes. After treatment with intravenous
      antibiotics and complete removal of shunt with subsequent replacement with a new
      ventriculoperitoneal shunt, the nephritic symptoms resolved, but the patient
      continued to have reduced kidney function consistent with stage IIIa chronic
      kidney disease. CONCLUSION: This case emphasizes the clinical importance of
      having a high index of suspicion in patients with a ventricular shunt who present
      with symptoms consistent with nephritis, even in the setting of negative cultures
      and delayed presentation.

PMID- 29325952
TI  - Endovascular Treatment of Intracranial Aneurysms Concomitant with Severe Adjacent
      Atherosclerotic Stenosis.
AB  - PURPOSE: To investigate the effect and safety of endovascular treatment of
      intracranial aneurysms concomitant with severe adjacent atherosclerotic stenosis.
      MATERIALS AND METHODS: Twenty-six patients with aneurysms and adjacent stenosis
      were prospectively enrolled. The characteristics of the aneurysm, parent artery,
      atherosclerotic stenosis and endovascular treatment methods were analyzed.
      RESULTS: All aneurysms were successfully embolized (100%), with stent-assisted
      coiling in 14 (53.8%) cases, coiling alone in 10 (38.5%), double microcatheter
      coiling in 1 (3.8%), and balloon-assisted coiling in the remaining 1 (3.8%).
      Immediately after embolization, complete occlusion was achieved in 10 cases
      (38.5%), nearly complete occlusion in 6 (23.1%) and non-complete occlusion in 10
      (38.5%). Ten aneurysms were type I and were managed with coiling alone in 8 cases
      and stent-assisted coiling in the remaining 2 cases, with complete occlusion
      achieved in 6 cases (60%), nearly complete in 2 (20%), and noncomplete in the
      other 2 (20%). Sixteen aneurysms were type II and treated with stent-assisted
      coiling in 12 cases (75%), single coiling in 2 (12.5%), double microcatheters in
      1 (6.3%), and balloon-assisted coiling in the remaining aneurysm (6.3%). Aneurysm
      occlusion was complete in 4 cases (25%), nearly complete in 4 (25%), and
      noncomplete in the other 8 (50%). Clinical follow-up of 2 months to 5 years (mean
      26 +/- 11 months) demonstrated no rebleeding, with the modified Rankin scale
      score of 0-2 in 20 patients, 3 in 4, and 6 in the remaining 2. CONCLUSIONS:
      Intracranial aneurysms concomitant with severe adjacent atherosclerotic stenosis
      can be successfully treated endovascularly, and careful evaluation of the
      characteristics of the aneurysm, parent artery, stenosis and collateral
      circulation can help reducing complications.

PMID- 29325953
TI  - Physical Risk Factors of Hemorrhagic Complications Associated with Angio-Seal
      Closure Device Use in Neurointerventional Procedures.
AB  - BACKGROUND: Few studies have demonstrated detailed physical risk factors of
      hemorrhagic complications (HCs) associated with the Angio-Seal closure device.
      This retrospective study aimed to identify the risk factors of HC due to Angio
      Seal use. METHODS: Data from 143 cases that underwent neurointerventional
      procedures that involved puncturing the femoral artery and that used an Angio
      Seal to close the puncture site were reviewed. We divided these cases into HC and
      no HC groups and retrospectively compared age, sex, past medical and preference
      history, body mass index (BMI), femoral artery depth, dual antiplatelet therapy
      use, activated clotting time, general anesthesia use, sheath size, right femoral
      artery puncture, and treatment time. RESULTS: HC occurred in 7 cases, 2 of which
      were excluded because of technical failure. Accordingly, we examined physical
      risk factors in 5 cases (3.5%) in the HC group and in 136 cases (96.5%) in the no
      HC group. A low BMI and shallow femoral artery depth were significantly
      associated with HC, whereas the other factors were not. A receiver operating
      characteristic curve indicated that a BMI cut-off value of 20.98 and a femoral
      artery depth of 11.1 mm could achieve optimal diagnostic efficiency for
      predicting HC. CONCLUSIONS: Patients with a BMI <21 may require careful
      hemostasis monitoring, and it is better not to undergo arterial puncture site
      closure using Angio-Seal for those with a femoral artery depth <11.1 mm.

PMID- 29325954
TI  - Anterior Skull Base Tumor Resection by Transciliary Supraorbital Keyhole
      Craniotomy: A Single Institutional Experience.
AB  - BACKGROUND: The prognosis and recurrence rate after resection of an anterior
      skull base lesion via transciliary supraorbital keyhole craniotomy depend on
      residual tumor volume. The extent to which pathology and size of tumor influence
      the resection rate using this approach is unknown. METHODS: Sixty-two patients
      underwent a total of 64 operations using the supraorbital keyhole approach in
      this retrospective study. Meningioma was the most common tumor, followed by
      pituitary adenoma and craniopharyngioma. Age, sex, tumor volume, operative
      duration, blood loss, and complication rates were evaluated. Pre- and
      postoperative residual tumor volumes were measured using OsiriX software (medical
      image viewer system) based on magnetic resonance imaging. A 15-mL cut value
      divided the subjects into large versus small meningioma groups. RESULTS: The
      average resection rate for meningiomas was 95.2% compared with 83.9% for
      craniopharyngiomas and 53.2% for pituitary adenomas. The major complication rate
      (primarily blindness and hemiplegia) was 4.48% in all tumors. No operative
      related deaths occurred. There were no surgical revisions to traditional large
      craniotomies. No significant differences in age, sex, postoperative volumes,
      resection rates, or recurrence rates were noted between small and large
      meningioma groups. However, longer operative times and hospital stays, and
      greater blood loss occurred in the large meningioma group. CONCLUSIONS:
      Transciliary keyhole craniotomy is a safe and effective approach for anterior
      skull base tumors, especially meningiomas. Excellent resection results were
      achieved even in cases of large meningiomas. Although longer operative times,
      longer hospital stays, and greater blood loss occurred in larger compared with
      smaller meningioma cases, recurrence rates were similar.

PMID- 29325955
TI  - Endovascular Patch Embolization for Blood Blister-Like Aneurysms in Dorsal
      Segment of Internal Carotid Artery.
AB  - OBJECTIVE: Blood blister-like aneurysms (BBAs) in the dorsal segment of the
      internal carotid artery are fragile and difficult to treat, and the optimal
      treatment for BBAs is still controversial. We report clinical and angiographic
      results with procedural details for the treatment of BBA by using the
      endovascular patch embolization method. METHODS: We retrospectively reviewed
      patients who presented with subarachnoid hemorrhage caused by internal carotid
      artery-BBAs and were treated with the endovascular patch embolization method in
      our center from October 2011 to March 2015. Clinical records, angiographic
      findings, procedural details, and follow-up results are reported in this study.
      RESULTS: Eight patients were enrolled in this study. All patients were treated
      with the endovascular patch embolization method. The key points of this method
      are step-by-step stent deployment and swaying of the microcatheter to coil the
      aneurysm sac and the wedge-shaped space between the stent and parent artery and,
      thereby, in the aneurysm sac and parent artery around the aneurysm neck. When the
      stent is completely deployed, an endovascular patch is formed and anchored around
      the neck of the BBA. The procedure was successful in all cases. No acute
      complications developed in any case. No rerupture or recurrence of the BBA
      occurred during follow-up. One patient with Hunt-Hess V subarachnoid hemorrhage
      died of multiple organ failure 4 months post treatment. Another patient died of
      intracranial infection related to the ventricle-peritoneal shunt. The remaining 6
      patients had good clinical outcomes (modified Rankin Scale score of zero).
      CONCLUSION: Endovascular patch embolization is an improvement on stent-assisted
      coil embolization, which could be successfully performed only with extensive
      skill and patience. Endovascular patch embolization could be an effective method
      in BBA treatment. However, its efficacy and safety should be verified in a larger
      patient cohort and long-term follow-up study.

PMID- 29325956
TI  - Rapid-Onset Thoracic Myelopathy due to an Epidural Sarcoid-Like Lesion in a
      Pediatric Patient.
AB  - BACKGROUND: Isolated intraspinal neurosarcoidosis is a rare clinical entity, with
      most reports describing intramedullary involvement in adults. CASE DESCRIPTION:
      We detail the case of a 9-year-old girl with rapid-onset compressive myelopathy
      secondary to a thoracic epidural lesion. Although pathologic diagnosis was
      challenging, a presumptive diagnosis of isolated extradural neurosarcoidosis was
      made in light of the patient's investigations and dramatic response to
      corticosteroids. CONCLUSIONS: Although less likely than neoplasia, rheumatologic
      processes such as inflammatory granulomatous disease warrant consideration in
      similar cases.

PMID- 29325957
TI  - Effect and Feasibility of Therapeutic Hypothermia in Patients with Hemorrhagic
      Stroke: A Systematic Review and Meta-Analysis.
AB  - INTRODUCTION: Therapeutic hypothermia (TH) has shown good results in experimental
      models of hemorrhagic stroke. The clinical application of TH, however, remains
      controversial, since reports regarding its therapeutic effect are inconsistent.
      METHODS: We conducted a systematic review based on Preferred Reporting Items for
      Systematic Reviews and Meta-analyses comparing TH with a control group in terms
      of mortality, poor outcome, delayed cerebral ischemia (DCI), and specific
      complications. The subgroup analyses were stratified by study type, country, mean
      age, hemorrhage type, cooling method, treatment duration, rewarming velocity, and
      follow-up time. RESULTS: Nine studies were included, most of which were of
      moderate quality. The overall effect demonstrated insignificant differences in
      mortality (risk ratio [RR] 0.78; 95% confidence interval [CI] 0.58-1.06; P =
      0.11) and poor outcome rate (RR 0.89; 95% CI 0.70-1.12; P = 0.32) between TH and
      the control group. However, sensitivity analyses, after we omitted 1 study,
      achieved a statistically significant difference in poor outcome favoring TH.
      Moreover, in the subgroup analyses, the results derived from randomized studies
      revealed that TH significantly reduced poor outcomes (RR 0.40; 95% CI 0.22-0.74;
      P = 0.003). In addition, TH significantly reduced DCI compared with control (RR
      0.61; 95% CI 0.40-0.93; P = 0.02). The incidence of specific complications
      (rebleeding, pneumonia, sepsis, arrhythmia, and hydrocephalus) between the 2
      groups were comparable and did not reach significant difference. CONCLUSIONS: The
      overall effect showed TH did not significantly reduce mortality and poor outcomes
      but led to a decreased incidence of DCI. Compared with control, TH resulted in
      comparable incidences of specific complications.

PMID- 29325958
TI  - Novel Assessment of Cerebrospinal Fluid Dynamics by Time-Spatial Labeling
      Inversion Pulse Magnetic Resonance Imaging in Patients with Chiari Malformation
      Type I.
AB  - OBJECTIVE: We investigated cerebrospinal fluid (CSF) dynamics at the
      craniocervical junction (CCJ) using Time-SLIP magnetic resonance imaging to
      demonstrate the significance of ventral and dorsal combined CSF dynamics in
      assessing CSF flow disturbance in patients with Chiari malformation type I.
      METHODS: Fifteen examinations were performed in 9 cases of CM-I (3 female
      patients; mean age, 24.7 years; age range, 11-46 years) before or after
      craniocervical decompression. The longitudinal maximum movement of the caudal
      edge of tagged midsagittal CSF at the CCJ was measured as length of motion (LOM),
      and total on the ventral and dorsal sides was defined as total LOM. RESULTS: In 8
      conditions, where it was concluded that no craniocervical decompression was
      necessary or where symptoms improved following craniocervical decompression based
      on the clinical symptoms, total LOM was 49.8 +/- 13.1 mm. In contrast, in the 7
      cases where craniocervical decompression was mandatory, total LOM was 23.2 +/-
      9.2 mm. Significant differences were identified between the 2 groups. Total LOM
      <35.0 mm resulted to indicate the insufficiency of CSF dynamics, because it
      corresponded to the necessity of craniocervical decompression based on patients'
      symptoms. CONCLUSIONS: Time-SLIP MRI enabled clinicians to use novel dynamic
      indices, such as CSF motions, in addition to the conventional findings acquired
      by MRI. In particular, it was essential to examine combined ventral and dorsal
      CSF dynamics in assessing CSF patency at the CCJ in patients with CM-I.

PMID- 29325959
TI  - Agreement Between Extent of Meningioma Resection Based on Surgical Simpson Grade
      and Based on Postoperative Magnetic Resonance Imaging Findings.
AB  - BACKGROUND: The surgical Simpson grade, introduced in 1957, is the standard
      measure for meningioma resection and prediction of recurrences. We used an
      magnetic resonance (MR)-based grading system for the radiologic extent of
      resection, and assessed agreement of the extent of resection between the surgical
      Simpson grade and the MR-based scale. METHODS: Patients were prospectively
      included during a 2-year period. Immediately after surgery, the surgeon
      determined the Simpson grade. MR imaging was performed within 72 hours and at 3
      months after surgery. Scans were assessed by a neuroradiologist, blinded to the
      surgeon's grading. Intraclass correlation coefficient (ICC) and absolute
      agreement were used to evaluate agreement between both scales. RESULTS: Thirty
      five patients (41 tumors) were included. Absolute agreement was 76%, with an ICC
      of 0.613. At 3 months postoperatively, the ICC and absolute agreement were 0.682
      and 78%. In 20% of cases, the extent of resection was less favorable on the early
      postoperative MR imaging than the surgeon's Simpson grade. CONCLUSIONS: Agreement
      for extent of meningioma resection between both scales was good in terms of the
      ICC. When the surgical Simpson grade is unclear, MR imaging at 3 months after
      surgery may be used as a baseline for further follow-up. In a substantial portion
      of cases, the extent of resection was less favorable on the early postoperative
      MR imaging than the surgeon's Simpson grade. The predictive value of the
      radiologic extent of resection for the risk of long-term recurrences is a subject
      for further research.

PMID- 29325960
TI  - Results of Biopsy-Proven Sellar Germ Cell Tumors: Nine Years' Experience in a
      Single Center.
AB  - BACKGROUND: The biopsy is recognized as the most accurate method to determine the
      histologic characterization of sellar germ cell tumors. It is difficult to
      evaluate the prognosis before histologic confirmation. OBJECTIVE: This study
      aimed to evaluate the independent prognostic risk factors of patients with sellar
      germ cell tumors (GCTs). METHODS: From January 2008 to December 2015, 61 patients
      who were histologically diagnosed as having sellar GCTs were followed up and were
      included in this retrospective study. RESULTS: Of 61 patients in this study, 40
      (65.6%), 10 (16.4%), and 11 (18.0%) were diagnosed as having pure germinomas,
      germinomas with syncytiotrophoblastic giant cells and non-germinomatous GCTs
      (NGGCTs), respectively. The patients with pure germinomas had a significantly
      better overall survival time than did those with NGGCT (56.47 +/- 3.01 months vs.
      43.09 +/- 10.58 months; P = 0.01). Multivariate analysis showed that the
      independent poor prognostic risk factors of patients with sellar GCTs were
      diameters >15 mm (odds ratio [OR], 7.40; 95% confidence interval [CI], 2.01
      27.19), octamer-binding transcription positivity (OR, 5.97; 95% CI, 1.40-25.48),
      and NGGCT (OR, 11.88; 95% CI, 2.37-59.50), whereas the combination of
      chemotherapy and radiotherapy was associated with a better prognosis (OR, 0.15;
      95% CI, 0.04-0.55). CONCLUSIONS: Diameter >15 mm, octamer-binding transcription
      positivity, or NGGCT was associated with a poorer prognosis for patients with
      sellar GCTs, whereas the combination of chemotherapy and radiotherapy was
      associated with a better prognosis.

PMID- 29325961
TI  - Abdominal Pseudocysts and Peritoneal Catheter Revisions: Surgical Long-Term
      Results in Pediatric Hydrocephalus.
AB  - OBJECTIVE: An abdominal pseudocyst (APC) is a distal catheter site-specific
      failure in patients treated with ventriculoperitoneal shunts. Few studies with
      more than 10 patients have been reported. The aim of this study was to analyze
      causes of peritoneal catheter revisions with special emphasis on revisions
      because of an APC. METHODS: Pediatric patients with first shunt operation between
      1982 and 1992 were included, and time, cause, and modality of peritoneal catheter
      revision were determined retrospectively. RESULTS: One hundred thirty-eight
      patients were treated for hydrocephalus, and 112 patients received a peritoneal
      catheter during the follow-up. An APC was diagnosed in 14 (12.5%) patients, and
      28 revisions were needed for its treatment. The rate of shunt infection in
      patients with APC was 50%, but bacterial examination of the pseudofluid culture
      revealed infection in only 3 patients. Age at first surgical procedure, type of
      first surgical procedure, and etiology of hydrocephalus were not associated with
      APC diagnosis. APC recurred in 4 patients. These patients had a catheter
      repositioning directly into the peritoneum as first surgical treatment. No
      recurrences were observed in patients with shunt externalization or replacement
      of the peritoneal catheter. CONCLUSIONS: An APC is a major long-term complication
      after ventriculoperitoneal shunt treatment. Although a sterile inflammatory
      response cannot be excluded completely, our results favor the hypothesis of low
      level shunt infection. In both cases, the surgical consequences are the same. An
      infected APC should be treated as a shunt infection. Uninfected patients can be
      treated with shunt externalization and replacement of only the peritoneal
      catheter.

PMID- 29325963
TI  - Surgical Anatomy of the Eustachian Tube for Endoscopic Transnasal Skull Base
      Surgery: A Cadaveric and Radiologic Study.
AB  - OBJECTIVE: The endoscopic endonasal approach to the anatomically complex lateral
      skull base presents technical challenges. The use of the eustachian tube as a
      landmark to identify the petrous internal carotid artery has recently been
      reported, and this study aims to define the anatomic relationship between the
      eustachian tube and its surrounding structures using cadaveric dissection and
      radiologic analysis. METHODS: To clarify the relationship of the eustachian tube
      with its surrounding structures, we performed endoscopic and microscopic
      dissection of 4 adult cadaveric heads and analyzed computed topography scans from
      20 patients. RESULTS: The eustachian tube is divided into the osseous and
      cartilaginous parts. The cartilaginous part can be further subdivided into the
      posterolateral, middle, and anteromedial parts, based on its relationship to the
      skull base. The eustachian tube is closely related to the pterygoid process of
      the sphenoid bone, the foramen lacerum, and the petrosal apex and is directed
      away from the oblique sagittal plane almost parallel to the vidian canal at 12.2
      degrees  +/- 6.2 degrees  (mean +/- standard deviation). The relationship between
      the course of the vidian canal and the eustachian tube can aid the estimation of
      the anatomic course of the horizontal segment of the petrous carotid artery.
      CONCLUSIONS: The eustachian tube is a useful landmark for predicting the course
      of the internal carotid artery when accessing the lateral skull base regions via
      an endonasal route. A profound understanding of the relationship between the
      eustachian tube and the surrounding skull base structures is important for
      endoscopic endonasal skull base surgeries.

PMID- 29325962
TI  - Systematic Review of Factors Influencing Surgical Performance: Practical
      Recommendations for Microsurgical Procedures in Neurosurgery.
AB  - BACKGROUND: Microneurosurgical techniques involve complex manual skills and hand
      eye coordination that require substantial training. Many factors affect
      microneurosurgical skills. The goal of this study was to use a systematic
      evidence-based approach to analyze the quality of evidence for intrinsic and
      extrinsic factors that influence microneurosurgical performance and to make
      weighted practical recommendations. METHODS: A literature search of factors that
      may affect microsurgical performance was conducted using PubMed and Embase. The
      criteria for inclusion were established in accordance with the PRISMA-P
      (Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols)
      statement. RESULTS: Forty-eight studies were included in the analysis. Most of
      the studies used surgeons as participants. Most used endoscopic surgery
      simulators to assess skills, and only 12 studies focused on microsurgery. This
      review provides 18 practical recommendations based on a systematic literature
      analysis of the following 8 domains: 1) listening to music before and during
      microsurgery, 2) caffeine consumption, 3) beta-blocker use, 4) physical exercise,
      5) sleep deprivation, 6) alcohol consumption before performing surgery, 7)
      duration of the operation, and 8) the ergonomic position of the surgeon.
      CONCLUSIONS: Despite the clear value of determining the effects of various
      factors on surgical performance, the available body of literature is limited, and
      it is not possible to determine standards for each surgical field. These
      recommendations may be used by neurosurgical trainees and practicing
      neurosurgeons to improve microsurgical performance and acquisition of
      microsurgical skills. Randomized studies assessing the factors that influence
      microsurgical performance are required.

PMID- 29325965
TI  - Genome-wide association mapping for seed protein and oil contents using a large
      panel of soybean accessions.
AB  - Soybean is globally cultivated primarily for its protein and oil. The protein and
      oil contents of the seeds are quantitatively inherited traits determined by the
      interaction of numerous genes. In order to gain a better understanding of the
      molecular foundation of soybean protein and oil content for the marker-assisted
      selection (MAS) of high quality traits, a population of 185 soybean germplasms
      was evaluated to identify the quantitative trait loci (QTLs) associated with the
      seed protein and oil contents. Using specific length amplified fragment
      sequencing (SLAF-seq) technology, a total of 12,072 single nucleotide
      polymorphisms (SNPs) with a minor allele frequency (MAF) >= 0.05 were detected
      across the 20 chromosomes (Chr), with a marker density of 78.7 kbp. A total of 31
      SNPs located on 12 of the 20 soybean chromosomes were correlated with seed
      protein and oil content. Of the 31 SNPs that were associated with the two target
      traits, 31 beneficial alleles were identified. Two SNP markers, namely rs15774585
      and rs15783346 on Chr 07, were determined to be related to seed oil content both
      in 2015 and 2016. Three SNP markers, rs53140888 on Chr 01, rs19485676 on Chr 13,
      and rs24787338 on Chr 20 were correlated with seed protein content both in 2015
      and 2016. These beneficial alleles may potentially contribute towards the MAS of
      favorable soybean protein and oil characteristics.

PMID- 29325964
TI  - Spontaneous Repeated Disappearance and Recurrence of Multiple Spinal Intradural
      Arachnoid Cysts in a Child.
AB  - BACKGROUND: Spinal intradural arachnoid cysts are rare in the pediatric
      population. We present a rare case of intradural spinal arachnoid cysts that
      spontaneously and repeatedly disappeared and reoccurred. CASE DESCRIPTION: A 2
      year-and-8-months-old boy presenting with lower extremity weakness was found to
      have spinal intradural arachnoid cysts in cervical and thoracolumbar regions at
      separate times. Although spontaneous disappearance of both lesions was observed,
      surgical treatment was finally performed for the symptomatic recurrent
      thoracolumbar lesion. CONCLUSIONS: To the best of our knowledge, this is the
      first report of spontaneously disappearing and recurring spinal arachnoid cysts.

PMID- 29325966
TI  - Role of Intraoperative Ultrasound to Extend the Application of Minimally Invasive
      Surgery for Treatment of Recurrent Gynecologic Cancer.
AB  - STUDY OBJECTIVE: To describe the potential role of intraoperative ultrasound
      (IOUS) in the detection and localization of recurrent disease in gynecologic
      cancer patients during minimally invasive surgery (MIS). DESIGN: A prospective
      cohort study (Canadian Task Force classification II-1). SETTING: A university
      hospital. PATIENTS: Fifty-one gynecologic cancer patients with isolated recurrent
      disease. INTERVENTIONS: IOUS during secondary cytoreductive surgery (SCS) by MIS.
      MEASUREMENTS AND MAIN RESULTS: From November 2015 to February 2017 51 gynecologic
      cancer patients with isolated recurrent disease and candidates for SCS were
      treated by MIS. Recurrent tumor was preoperatively assessed at clinical
      examination, transvaginal and transabdominal sonography, and radiologic
      evaluation in all women. Twelve of 51 women (23.5%) needed IOUS. Type of disease
      was ovarian in 5 women (42%), endometrial in 4 (33%), cervical in 1 (8%), vaginal
      cancer in 1 (8%), and uterine sarcoma in 1 (8%). Recurrence was localized deep in
      the pelvis in 7 cases (58%), lymph nodes in 3 (25%), and extraperitoneal in 2
      cases (17%). Recurrence was dimmed in the surgical field, due to either presence
      of adherences, deep anatomic position, small size, and/or lack of tactile
      feeling. IOUS was able to identify the lesions in all women, allowing MIS (83%
      laparoscopy and 17% robotic) complete cytoreduction, with no conversion to
      laparotomy. Median operative time was 150 minutes (range, 77-280). No
      intraoperative/postoperative complications occurred. Histologic examination
      confirmed the presence of recurrence in 11 of 12 cases (92%), whereas the
      remaining case showed inflammatory tissue. With a median follow-up time of 15
      months (range, 6-19), all patients except 2 were still alive. CONCLUSIONS: About
      1 of 4 patients (25%) with single gynecologic cancer recurrence needs IOUS to
      benefit from MIS for complete secondary cytoreduction.

PMID- 29325967
TI  - A Randomized Controlled Trial for Abdominal Binder Use after Laparoendoscopic
      Single-Site Surgery.
AB  - STUDY OBJECTIVE: To compare postoperative pain in patients using an abdominal
      binder with a control group after laparoendoscopic single-site (LESS) surgery.
      DESIGN: A randomized controlled trial (Canadian Task Force classification level
      1). SETTING: An academic gynecologic surgeon's practice. PATIENTS: Private
      patients undergoing surgery performed by a fellowship-trained minimally invasive
      gynecologic surgeon between April 2016 and April 2017. INTERVENTIONS: Ninety
      total patients were selected for this study, with 60 randomized to receive an
      abdominal binder after surgery and 30 patients randomized to the control group
      without a binder. MEASUREMENTS AND MAIN RESULTS: Using a 10-point verbal analog
      scale, patients recorded pain levels for 3 weeks postoperatively on a variety of
      measures, including overall and incisional pain. They recorded results on
      postoperative days 0, 1, 2, 3, 4, 7, 14, and 21. On average, the association
      between time and the overall pain score did not differ with binder use (p = .37).
      The overall pain decreases significantly over time (p < .001). After adjusting
      for time, the overall pain score differed significantly by binder status (p =
      .04). Those without a binder reported an average pain score that was 1.13
      (standard deviation = 0.55) points higher than those with a binder across the
      first week. CONCLUSION: The results suggest that abdominal binder use after LESS
      surgery may be beneficial in reducing postoperative pain in the first week.
      Results from this study can provide feasibility data for future studies.

PMID- 29325968
TI  - Regarding "Accuracy of Tubal Patency Assessment during Diagnostic Hysteroscopy
      Compared with Laparoscopy in Infertile Women: A Retrospective Cohort Study".

PMID- 29325969
TI  - Population structure and genetic diversity of Rhipicephalus microplus in
      Zimbabwe.
AB  - Recently there was an expansion in the geographic range of Rhipicephalus
      microplus in Zimbabwe. In order to understand gene flow patterns and population
      structure in this highly invasive and adaptable cattle tick, a population
      genetics study was carried out. Eighty-seven R. microplus tick samples drawn from
      5 distinct populations were genotyped using eight polymorphic microsatellite
      loci. Genetic diversity (He) was high (0.755-0.802) in all the populations,
      suggesting high levels of gene flow with 97% of genetic variation found within
      populations and 3% amongst populations. No isolation by distance was observed
      with low but significant genetic differentiation amongst the populations (0
      0.076). Most of the sampled individuals had admixed genetic backgrounds, except
      for those from Matabeleland North whose genetic makeup appeared different from
      the rest. Rhipicephalus microplus was recently recorded in this area and the
      environmental conditions do not support survival of the tick there. These results
      confirm recent range expansion of the tick and the lowest genetic diversity
      recorded in the Matabeleland North population is suggestive of a founder effect,
      which may lead to genetic drift. Generally, the very low levels of genetic
      differentiation amongst the populations could be a result of the frequent
      movement of livestock from one area to another, which will have implications for
      disease control. This study offers further opportunities to study evolutionary
      adaptation of R. microplus in Zimbabwe and southern Africa.

PMID- 29325971
TI  - Incorporation of fetal and child PFOA dosimetry in the derivation of health-based
      toxicity values.
AB  - BACKGROUND: Multiple agencies have developed health-based toxicity values for
      exposure to perfluorooctanoic acid (PFOA). Although PFOA exposure occurs in utero
      and through breastfeeding, current health-based toxicity values have not been
      derived using fetal or child dosimetry. Therefore, current values may
      underestimate the potential risks to fetuses and nursing infants. OBJECTIVE:
      Using fetal and child dosimetry, we aimed to calculate PFOA maternal human
      equivalent doses (HEDs), corresponding to a developmental mouse study lowest
      observed adverse effect level (LOAEL, 1mg/kg/day). Further, we investigated the
      impact of breastfeeding duration and PFOA half-life on the estimated HEDs.
      METHODS: First, a pharmacokinetic model of pregnancy and lactation in mice was
      used to estimate plasma PFOA levels in pups following a maternal exposure to 1mg
      PFOA/kg/day for gestational days 1-17. Four plasma PFOA concentration metrics
      were estimated in pups: i) average prenatal; ii) average postnatal; iii) average
      overall (prenatal and postnatal); and iv) maximum. Then, Monte Carlo simulations
      were performed using a pharmacokinetic model of pregnancy and lactation in humans
      to generate distributions of maternal HEDs that would result in fetal/child
      plasma levels equivalent to those estimated in pups using the mouse model. Median
      (HED50) and 1st percentile (HED01) of calculated HEDs were calculated. RESULTS:
      Estimated PFOA maternal HED50s ranged from 3.0*10-4 to 1.1*10-3mg/kg/day and
      HED01s ranged from 4.7*10-5 to 2.1*10-4mg/kg/day. All calculated HEDs were lower
      than the HED based on adult dosimetry derived by the Environmental Protection
      Agency (EPA) (5.3*10-3mg/kg/day). CONCLUSION: Our results suggest that
      fetal/child dosimetry should be considered when deriving health-based toxicity
      values for potential developmental toxicants.

PMID- 29325972
TI  - Antioxidant activity of CAPE (caffeic acid phenethyl ester) in vitro can protect
      human sperm deoxyribonucleic acid from oxidative damage.
AB  - PURPOSE: Sperm processing (e.g., centrifugation) used in preparation for assisted
      reproduction can result in excessive generation of reactive oxygen species (ROS)
      and potential sperm damage. The use of antioxidants during sperm processing has
      been shown to prevent iatrogenic sperm damage, including DNA damage. In this
      study, we evaluated the effect of caffeic acid phenethyl ester (CAPE) on
      oxidative stress mediated sperm dysfunction and DNA damage. METHODS: Semen
      samples were obtained to liquefy at room temperature. After centrifugation and
      washing protocols, spermatozoa were incubated in a single step supplemented
      medium with either of 10, 50 or 100 MUmol/L CAPE for 2 hours at 36  degrees C.
      After incubation period, MDA levels of seminal plasma were measured. The
      fragmentation in sperm DNA was detected by light microscopy via use of an aniline
      blue assay, while ultrastructural morphology was analyzed by transmission
      electron microscopy. RESULTS: Significant increase has been observed in percent
      chromatin condensation (assessed by aniline blue staining) and Malondialdehyde
      (Mmol/L) in oligoasthenoteratozoospermia group before the centrifugation (0.57 +/
      0.15). Incubation of samples with 100 MUmol/L CAPE after centrifugation resulted
      in a significantly lower percent chromatin condensation compared to samples
      incubated without CAPE (0.42 +/- 0.12) (P < 0.0033). Incubation of all samples
      with CAPE (10 MUmol/L, 50 MUmol/L, 100 MUmol/L.) after centrifugation resulted in
      a significantly lower percentage of Malondialdehyde levels. CONCLUSIONS: The data
      suggests that preincubation of spermatozoa with the antioxidant CAPE offers
      protection against oxidative DNA damage in vitro.

PMID- 29325973
TI  - Cardiac electronic implantable devices after tricuspid valve surgery.
AB  - The demand for tricuspid valve (TV) surgery has increased continuously in the
      last years. Recent registry data have confirmed that TV repair or replacement
      carry an increased risk of conduction disorders requiring permanent pacemaker
      implantation, specifically for patients having multivalve surgery. The
      implantation of an endocardial right ventricular lead in those patients may
      impair TV function, and some other approaches may be discussed to avoid
      traversing the valve. This contemporary review describes the different options
      currently available for patients requiring pacemaker or defibrillation leads
      implantation after TV surgery.

PMID- 29325970
TI  - The role of adjuvant immunomodulatory agents for treatment of severe influenza.
AB  - A severe inflammatory immune response with hypercytokinemia occurs in patients
      hospitalized with severe influenza, such as avian influenza A(H5N1), A(H7N9), and
      seasonal A(H1N1)pdm09 virus infections. The role of immunomodulatory therapy is
      unclear as there have been limited published data based on randomized controlled
      trials (RCTs). Passive immunotherapy such as convalescent plasma and hyperimmune
      globulin have some studies demonstrating benefit when administered as an
      adjunctive therapy for severe influenza. Triple combination of oseltamivir,
      clarithromycin, and naproxen for severe influenza has one study supporting its
      use, and confirmatory studies would be of great interest. Likewise, confirmatory
      studies of sirolimus without concomitant corticosteroid therapy should be
      explored as a research priority. Other agents with potential immunomodulating
      effects, including non-immune intravenous immunoglobulin, N-acetylcysteine, acute
      use of statins, macrolides, pamidronate, nitazoxanide, chloroquine, antiC5a
      antibody, interferons, human mesenchymal stromal cells, mycophenolic acid,
      peroxisome proliferator-activated receptors agonists, non-steroidal anti
      inflammatory agents, mesalazine, herbal medicine, and the role of plasmapheresis
      and hemoperfusion as rescue therapy have supportive preclinical or observational
      clinical data, and deserve more investigation preferably by RCTs. Systemic
      corticosteroids administered in high dose may increase the risk of mortality and
      morbidity in patients with severe influenza and should not be used, while the
      clinical utility of low dose systemic corticosteroids requires further
      investigation.

PMID- 29325975
TI  - Procedural outcomes and long-term survival associated with lead extraction in
      patients with abandoned leads.
AB  - BACKGROUND: The decision to abandon or extract superfluous sterile leads is
      controversial. OBJECTIVE: The purpose of this study was to compare procedural
      outcomes and long-term survival of patients with and those without abandoned
      leads undergoing lead extraction (LE). METHODS: Retrospective review of all
      patients who had undergone transvenous LE at our institution from January 2007 to
      May 2016 was performed. Patients were stratified into 2 groups based on the
      presence (group 1) or absence (group 2) of abandoned leads. RESULTS: Among 774
      patients who had undergone LE procedures, 38 (4.9%) had abandoned leads (group
      1). Dwell time of the oldest extracted lead was longer in group 1 vs group 2 (7.6
      +/- 4.9 years vs 5.6 +/- 4.4 years; P = .017), as was infection as an indication
      for LE (76% vs 33%; P <.001). A bailout femoral approach was more commonly
      required in group 1 than in group 2 (18.4% vs 6%; P = .007). Complete procedural
      success rates were similar (92.1% in group 1 vs 95.0% in group 2; P = .439), but
      there was a trend toward lower clinical success in group 1 (92.1% vs 97.4%; P =
      .088), primarily due to failure to remove all hardware in the setting of
      infection. Major procedural complication rates were similar (2.6% in group 1 vs
      1.2% in group 2; P = .397), as was long-term survival (mean follow-up 2.3 +/- 2.2
      years). CONCLUSION: Abandoned leads at the time of LE were associated with
      increased procedural complexity, including a higher rate of bailout femoral
      extraction, and may be associated with lower clinical success. Among
      appropriately selected patients, consideration should be given to LE instead of
      abandonment.

PMID- 29325974
TI  - Fast nonclinical ventricular tachycardia inducible after ablation in patients
      with structural heart disease: Definition and clinical implications.
AB  - BACKGROUND: Noninducibility of ventricular tachycardia (VT) with an equal or
      longer cycle length (CL) than that of the clinical VT is considered the minimum
      ablation endpoint in patients with structural heart disease. Because their
      clinical relevance remains unclear, fast nonclinical VTs are often not targeted.
      However, an accepted definition for fast VT is lacking. The shortest possible CL
      of a monomorphic reentrant VT is determined by the ventricular refractory period
      (VRP). OBJECTIVE: The purpose of this study was to propose a patient-specific
      definition for fast VT based on the individual VRP (fVTVRP) and assess the
      prognostic significance of persistent inducibility after ablation of fVTVRP for
      VT recurrence. METHODS: Of 191 patients with previous myocardial infarction or
      with nonischemic cardiomyopathy undergoing VT ablation, 70 (age 63 +/- 13 years;
      64% ischemic) remained inducible for a nonclinical VT and composed the study
      population. FVTVRP was defined as any VT with CL <=VRP400 + 30 ms. Patients were
      followed for VT recurrence. RESULTS: After ablation, 30 patients (43%) remained
      inducible exclusively for fVTVRP and 40 (57%) for any slower VT. Patients with
      only fVTVRP had 3-year VT-free survival of 64% (95% confidence interval [CI] 46%
      82%) compared to 27% (95% CI 14%-48%) for patients with any slower remaining VT
      (P = .013). Inducibility of only fVTVRP was independently associated with lower
      VT recurrence (hazard ratio 0.38; 95% CI 0.19-0.86; P = .019). Among 36 patients
      inducible for any fVTVRP, only 1 had recurrence with fVTVRP. CONCLUSION: In
      patients with structural heart disease, inducibility of exclusively fVTVRP after
      ablation is associated with low VT recurrence.

PMID- 29325978
TI  - Management of cardiac implantable electronic devices in the presence of left
      ventricular assist devices.
AB  - Left ventricular assist devices (LVAD) are increasingly used in the management of
      patients with advanced heart failure. Many of these patients have or will be
      considered for a cardiac implantable electronic device (CIED) such as an
      implantable cardioverter-defibrillator or a cardiac resynchronization therapy
      device. Frequent interplay is often encountered due to the complexity of these
      devices and the underlying disease states. Proactive management strategies and an
      awareness of interactions may help reduce adverse events. Here we review the
      current literature, present management recommendations, and discuss potential
      future investigations for CIEDs in patients with LVADs.

PMID- 29325976
TI  - Profile of patients with Brugada syndrome presenting with their first documented
      arrhythmic event: Data from the Survey on Arrhythmic Events in BRUgada Syndrome
      (SABRUS).
AB  - BACKGROUND: Detailed information on the profile of patients with Brugada syndrome
      (BrS) presenting their first arrhythmic event (AE) after prophylactic
      implantation of an implantable cardioverter-defibrillator (ICD) is limited.
      OBJECTIVES: The objectives of this study were (1) to compare clinical,
      electrocardiographic, electrophysiologic, and genetic profiles of patients who
      exhibited their first documented AE as aborted cardiac arrest (group A) with
      profiles of those in whom the AE was documented after prophylactic ICD
      implantation (group B) and (2) to characterize group B patients' profile using
      the class II indications for ICD implantation established by HRS/EHRA/APHRS
      expert consensus statement in 2013. METHODS: A survey of 23 centers from 10
      Western and 4 Asian countries enabled data collection of 678 patients with BrS
      who exhibited their AE (group A, n = 426; group B, n = 252). RESULTS: The first
      AE occurred in group B patients 6.7 years later than in group A (mean age 46.1 +/
      13.3 years vs 39.4 +/- 15.1 years; P < .001). Group B patients had a higher
      incidence of family history of sudden cardiac death and SCN5A mutations. Of the
      252 group B patients, 189 (75%) complied with the HRS/EHRA/APHRS indications
      whereas the remaining 63 (25%) did not. CONCLUSION: Patients with BrS with the
      first AE documented after prophylactic ICD implantation exhibited their AE at a
      later age with a higher incidence of positive family history of sudden cardiac
      death and SCN5A mutations as compared with those presenting with aborted cardiac
      arrest. Only 75% of patients who exhibited an AE after receiving a prophylactic
      ICD complied with the 2013 class II indications, suggesting that efforts are
      still required for improving risk stratification.

PMID- 29325979
TI  - An unusual case of complete atrioventricular block causing Takotsubo syndrome.
AB  - Complete atrioventricular (AV) block in association with Takotsubo syndrome (TS)
      has been well recognized, but the cause and effect relationship has not been
      elucidated. We describe a 78-year-old female who presented with complete AV block
      but one week later developed new-onset, diffuse T-wave inversions, QT
      prolongation, and acceleration of junctional escape rate. Left ventriculogram
      revealed features typical of TS. One year after permanent pacemaker implantation,
      complete AV block persisted despite the reversal of wall motion defects implying
      that conduction abnormality was the trigger of TS rather than its consequence.

PMID- 29325980
TI  - The emerging role of nanomaterials in immunological sensing - a brief review.
AB  - Nanomaterials are beginning to play an important role in the next generation of
      immunological assays and biosensors, with potential impacts both in research and
      clinical practice. In this brief review, we highlight two areas in which
      nanomaterials are already making new and important contributions in the past 5-10
      years: firstly, in the improvement of assay and biosensor sensitivity for
      detection of low abundance proteins of immunological significance, and secondly,
      in the real-time and continuous monitoring of protein secretion from arrays of
      individual cells. We finish by challenging the immunology/sensing communities to
      work together to develop nanomaterials that can provide real-time, continuous,
      and sensitive molecular readouts in vivo, a lofty goal that will require
      significant collaborative effort.

PMID- 29325981
TI  - "Spiked Helmet" electrocardiogram sign in a patient with takotsubo syndrome:
      Similarities with a previously described marker.

PMID- 29325977
TI  - Role of apamin-sensitive small conductance calcium-activated potassium currents
      in long-term cardiac memory in rabbits.
AB  - BACKGROUND: Apamin-sensitive small conductance calcium-activated K current (IKAS)
      is up-regulated during ventricular pacing and masks short-term cardiac memory
      (CM). OBJECTIVE: The purpose of this study was to determine the role of IKAS in
      long-term CM. METHODS: CM was created with 3-5 weeks of ventricular pacing and
      defined by a flat or inverted T wave off pacing. Epicardial optical mapping was
      performed in both paced and normal ventricles. Action potential duration (APD80)
      was determined during right atrial pacing. Ventricular stability was tested
      before and after IKAS blockade. Four paced hearts and 4 normal hearts were used
      for western blotting and histology. RESULTS: There were no significant
      differences in either echocardiographic parameters or fibrosis levels between
      groups. Apamin induced more APD80 prolongation in CM than in normal ventricles
      (mean [95% confidence interval]: 9.6% [8.8%-10.5%] vs 3.1% [1.9%-4.3%]; P <.001).
      Apamin significantly lengthened APD80 in the CM model at late activation sites,
      indicating significant IKAS up-regulation at those sites. The CM model also had
      altered Ca2+ handling, with the 50% Ca2+ transient duration and amplitude
      increased at distal sites compared to a proximal site (near the pacing site).
      After apamin, the CM model had increased ventricular fibrillation (VF)
      inducibility (paced vs control: 33/40 (82.5%) vs 7/20 (35%); P <.001) and longer
      VF durations (124 vs 26 seconds; P <.001). CONCLUSION: Chronic ventricular pacing
      increases Ca2+ transients at late activation sites, which activates IKAS to
      maintain repolarization reserve. IKAS blockade increases VF vulnerability in
      chronically paced rabbit ventricles.

PMID- 29325982
TI  - Multiple cerebral infarct with cerebral vasculitis in a young patient with
      ulcerative colitis.
AB  - Ulcerative colitis (UC) is a chronic and debilitating disorder, characterized by
      inflammation of the colonic mucosa. UC can be considered a systemic disorder but
      UC-related manifestations in the central nervous system (CNS) are quite rare. A
      29-year-old man was admitted to the emergency department with repeated
      generalized tonic-clonic (GTC) type seizures. Based on brain CT, brain metastasis
      or hemorrhagic infarct was suspected. Diffusion-weighted image of brain MRI
      showed high signal in the left thalamus and heterogenous enhancement in the right
      parietal and left frontal lobes. This image indicated a cerebral infarct, but
      could not completely rule out cerebral metastasis and vasculitis, or any other
      pathology. However, the brain biopsy revealed multiple thromboemboli with acute
      inflammation and necrosis. Thus, the patient was diagnosed with multiple cerebral
      infarcts with cerebral vasculitis, occurring as a complication of UC. In
      conclusion, CNS manifestations of UC are rare. However, clinicians should
      consider uncommon diagnoses like vasculitis and thromboembolism in patients with
      UC presenting with seizures.

PMID- 29325983
TI  - A Case of Delirium and Rhabdomyolysis in Severe Iatrogenic Opioid Withdrawal.

PMID- 29325984
TI  - Minimally Invasive Repair of Pectus Carinatum.
AB  - BACKGROUND: The second most common deformity of the anterior chest wall, pectus
      carinatum, is a diverse deformity that has been largely managed using open
      techniques. This study reviews clinical experience with a newly designed bar for
      minimally invasive repair of pectus carinatum. METHODS: We reviewed the records
      of all patients recorded in our Chest Wall Deformities Clinical Database. Between
      January 2006 and November 2016, minimally invasive repair of pectus carinatum was
      performed in 172 patients. All met the criteria of a "compression test" of 10 to
      25 kg/cm2. The mean age was 17.3 years, and 22.7% had a positive family history
      of a congenital chest wall deformity. Symmetric and asymmetric deformities were
      treated. During our study period, we designed 4 different bar configurations and
      their related stabilizers. All patients are assessed every 3 to 6 months. After 2
      to 3 years of follow-up, the bar and the stabilizers are removed. RESULTS: Of 172
      patients, 97.1% tolerated the procedure very well. The operation was a mean
      length 76.6 minutes. Average blood loss was 40 mL. Mean hospital length of stay
      was 3.7 days. Complications included pneumothorax, wire breakdown/rib cut, wound
      infection, severe pain, skin hyperpigmentation, nickel allergy, and
      overcorrection leading to excavatum. Patients returned to routine activity in 10
      to 14 days. With a mean follow-up of 29.8 months in bar removal patients, 130 of
      172 (93.8%) reported excellent results. CONCLUSIONS: Minimally invasive repair of
      pectus carinatum with the technically modified fourth-generation bar and its
      securing system has advantages of low morbidity, short hospital stay, and
      excellent cosmetic results, even in asymmetric cases.

PMID- 29325985
TI  - Platelet-Activating Antibodies Are Detectable at the Earliest Onset of Heparin
      Induced Thrombocytopenia, With Implications for the Operating Characteristics of
      the Serotonin-Release Assay.
AB  - BACKGROUND: Heparin-induced thrombocytopenia (HIT) is a prothrombotic drug
      reaction caused by platelet-activating antibodies that recognize platelet factor
      4 (PF4)/heparin complexes. It is unknown whether platelet-activating antibodies
      are detectable at the onset of the HIT-related platelet count fall. METHODS:
      Available blood samples from 18 patients obtained at onset of HIT were tested
      using the serotonin-release assay (SRA), a test for platelet-activating
      antibodies, and a PF4-dependent enzyme-linked immunosorbent assay (ELISA).
      Patient samples showing a delay of > 2 days between ELISA and SRA seroconversion
      were tested for subthreshold levels of platelet-activating antibodies using two
      modifications of the SRA that amplify detection of HIT antibodies. We also
      estimated SRA sensitivity and specificity in two postorthopedic surgery clinical
      trials (633 samples), including assessing whether a positive SRA influenced
      platelet count recovery in the absence of thrombocytopenia. RESULTS: Platelet
      activating HIT antibodies were detected in all 18 patients at the beginning of
      the HIT-related platelet count fall. Although ELISA seroconversion usually
      preceded SRA seroconversion by only 1 day (median), subthreshold levels of
      platelet-activating antibodies were detected in both patients who exhibited a lag
      between ELISA and SRA seroconversion. SRA sensitivity was 100% (18/18), and its
      specificity was 97% (597/615). Nonthrombocytopenic SRA-positive patients with
      ongoing heparin treatment exhibited blunted platelet count recovery vs control
      subjects, suggesting even higher SRA specificity for detecting abnormal platelet
      count profiles. CONCLUSIONS: Platelet-activating HIT antibodies are detectable at
      the onset of the HIT-related platelet count fall. The SRA has high sensitivity
      and specificity for HIT, and indicates that presence of HIT antibodies can blunt
      postoperative platelet count recovery.

PMID- 29325986
TI  - The Challenge of Rare Diseases.
AB  - Rare diseases pose particular challenges to patients who are affected, to the
      clinicians who care for them, and to the investigators who study their
      conditions. Although individually uncommon, rare diseases are common in the
      aggregate, with approximately 7,000 described rare diseases affecting 25 to 30
      million US adults. Challenges posed to affected individuals and their families
      largely regard being diagnosed, receiving optimal care, and affording disease
      specific medications. Challenges facing clinicians who care for affected
      individuals include gaining knowledge and experience in caring for such patients,
      and the availability of local experts and of expert guidelines. Finally,
      challenges to investigators regard the difficulty and expense of assembling large
      cohorts of affected individuals for study, and garnering funding for research.
      Fortunately, in the face of these challenges, the steadfast resolve of patient
      and clinical/scientific communities to enhance care and generate new knowledge
      has fostered a large inventory of countermeasures to offset these challenges.
      Although further progress is surely needed, successes to date include the
      formation of powerful patient advocacy groups which have brokered collaborations
      between the patient, scientific communities, the government, and pharma/device
      communities in service of detection, optimal care, and research; procurement of
      funds to support research; formation of consortia of clinicians and scientists to
      collaborate; and general activation of the respective patient communities to
      perpetuate these successes. Persisting needs include enhanced detection
      strategies, dissemination of knowledge regarding optimal care, and research to
      prevent, treat, and cure disease.

PMID- 29325987
TI  - Transfer of Pectobacterium carotovorum subsp. carotovorum strains isolated from
      potatoes grown at high altitudes to Pectobacterium peruviense sp. nov.
AB  - Seven Gram-negative, rod-shaped pectinolytic bacteria strains designated as
      IFB5227, IFB5228, IFB5229, IFB5230, IFB5231, IFB5232, IFB5636, isolated from
      potato tubers cultivated in Peru at high altitude (2400-3800m) were subjected to
      polyphasic analyses that revealed their distinctiveness from the other
      Pectobacterium species. Phylogenetic analyses based on five housekeeping genes
      (gyrA, recA, recN, rpoA and rpoS) clearly showed strains separateness,
      simultaneously indicating Pectobacterium atrosepticum, Pectobacterium wasabiae,
      Pectobacterium parmentieri and Pectobacterium betavasculorum as the closest
      relatives. In silico DNA-DNA hybridization of strain IFB5232T with other
      Pectobacterium type strains revealed significant drop in DDH value below 70%,
      which is a prerequisite to distinguish Pectobacterium peruviense. The ANI values
      supported the proposition of delineation of the P. peruviense. Genetic REP-PCR
      fingerprint and detailed MALDI-TOF MS proteomic profile sealed the individuality
      of the studied strains. However, phenotypic assays do not indicate immense
      differences. Provided results of analyses performed for seven Peruvian strains
      are the basis for novel species distinction and reclassification of the strains
      IFB5227-5232 and IFB5636, previously classified as Pectobacterium carotovorum
      subsp. carotovorum. Here, we propose to establish the IFB5232 isolate as a type
      strain (=PCM2893T=LMG30269T=SCRI179T) with the name Pectobacterium peruviense sp.
      nov.

PMID- 29325988
TI  - Arboriscoccus pini gen. nov., sp. nov., an endophyte from a pine tree of the
      class Alphaproteobacteria, emended description of Geminicoccus roseus, and
      proposal of Geminicoccaceae fam. nov.
AB  - Bacterial strain B29T1T was isolated from the endophytic microbial community of a
      Pinus pinaster tree trunk and characterized. Strain B29T1T stained Gram-negative
      and formed diplococci that grew optimally at 26-30 degrees C and at pH 6.0-7.0.
      The G+C content of the DNA was 61.6mol%. The respiratory quinone was ubiquinone
      10 (UK-10), and the major fatty acids were C16:0, cyclo-C19:0omega8c and C18:0 12
      methyl, representing 64% of the total fatty acids. Phylogenetic analyses based on
      the 16S rRNA gene sequences placed strain B29T1T within the order
      Rhodospirillales in a distinct lineage that also included the genus Geminicoccus.
      The 16S rRNA gene sequence similarities of B29T1T to that of Candidatus
      Alysiomicrobium bavaricum, Geminicoccus roseus and Candidatus Alysiosphaera
      europeae were 92.6%, 89.9% and 89.2%, respectively. The analysis of the available
      genomes from the closest families showed 177 core genes that reveals a novel
      family-level clade including the type strain of the genus Geminicoccus and the
      strain B29T1T. Analysis of B29T1T genome revealed all the genes involved in
      autotrophic carbon dioxide fixation via the reductive pentose phosphate pathway
      and genes encoding for starch/glycogen and chitin degradation. The phylogenetic,
      phenotypic and chemotaxonomic data showed that strain B29T1T (=CIP 110763T, =LMG
      27745T) represents the type of a novel species and genus, for which we propose
      the name Arboriscoccus pini gen. nov., sp. nov. A new family (Geminicoccaceae
      fam. nov.) is proposed for Arboriscoccus, Geminicoccus, Candidatus
      Alysiomicrobium and Candidatus Alysiosphaera. The description of the Geminicoccus
      roseus DSM 18922T is also emended.

PMID- 29325989
TI  - Proteomic analysis reveals the important roles of alpha-5-collagen and ATP5beta
      during skin ulceration syndrome progression of sea cucumber Apostichopus
      japonicus.
AB  - : Apostichopus japonicus is one of the most important aquaculture species in
      China. Skin ulceration syndrome (SUS) of sea cucumber is a common and serious
      disease affected the development of A. japonicus culture industry. To better
      understand the response mechanisms of A. japonicus during SUS progression, the
      protein variations in the body wall of A. japonicus at different stages of SUS
      were investigated by a comparative proteomic approach based on isobaric tags for
      relative and absolute quantification. A total of 1449 proteins were identified
      from the samples at different SUS stages. Among these proteins, 145 proteins were
      differentially expressed in the SUS-related samples compared to those of healthy
      A. japonicus. These differentially expressed proteins involved a wide range of
      functions. Among these differentially expressed proteins, only two proteins,
      alpha-5-collagen and an unknown function protein, were differentially expressed
      during the whole progression of SUS compared with healthy A. japonicus. In
      addition, ATP synthase subunit beta (ATP5beta) interacted with a variety of
      proteins with different functions during the SUS progression. These results
      implied that alpha-5-collagen and ATP5beta could play important roles during the
      SUS progression of A. japonicus. Our study provided a new sight to understand the
      molecular responses of sea cucumber during the SUS progression and accumulated
      data for the prevention of SUS in sea cucumber aquaculture. BIOLOGICAL
      SIGNIFICANCE: The current study aimed to reveal how the body wall of Apostichopus
      japonicus response to skin ulceration syndrome (SUS). To the best of our
      knowledge, this is the first proteomic study analyzing the differences in protein
      profile of sea cucumber during the whole SUS progression. By analyzing the
      expression differences of the proteome via isobaric labeling-based quantitative
      proteomic, we identified some proteins which may play important roles during the
      SUS progression. According to the enrichment analyses of these proteins based on
      Gene Ontology and Kyoto Encyclopedia of Genes and Genomes, a draft view of how
      the sea cucumber affected by SUS has been drawn. The common and unique
      differentially expressed proteins by Venn analysis showed that alpha-5-collagen
      was down-regulated at all stages of SUS, which had the potential as a target
      component for the host-directed SUS therapy. In addition, ATP5beta, a subunit of
      mitochondrial ATP synthase, interacting with a variety of proteins with different
      functions during the SUS progression. This result illustrated that energy
      production and metabolism could play an important role in the formation of skin
      ulceration and resistance to pathogens in sea cucumber. The results of this study
      will be helpful for researchers to gain insights into the complex molecular
      mechanism of SUS in sea cucumber.

PMID- 29325990
TI  - Quantitative proteomics reveals a role of JAZ7 in plant defense response to
      Pseudomonas syringae DC3000.
AB  - : Jasmonate ZIM-domain (JAZ) proteins are key transcriptional repressors
      regulating various biological processes. Although many studies have studied JAZ
      proteins by genetic and biochemical analyses, little is known about JAZ7
      associated global protein networks and how JAZ7 contributes to bacterial pathogen
      defense. In this study, we aim to fill this knowledge gap by conducting unbiased
      large-scale quantitative proteomics using tandem mass tags (TMT). We compared the
      proteomes of a JAZ7 knock-out line, a JAZ7 overexpression line, as well as the
      wild type Arabidopsis plants in the presence and absence of Pseudomonas syringae
      DC3000 infection. Both pairwise comparison and multi-factor analysis of variance
      reveal that differential proteins are enriched in biological processes such as
      primary and secondary metabolism, redox regulation, and response to stress. The
      differential regulation in these pathways may account for the alterations in
      plant size, redox homeostasis and accumulation of glucosinolates. In addition,
      possible interplay between genotype and environment is suggested as the abundance
      of seven proteins is influenced by the interaction of the two factors.
      Collectively, we demonstrate a role of JAZ7 in pathogen defense and provide a
      list of proteins that are uniquely responsive to genetic disruption, pathogen
      infection, or the interaction between genotypes and environmental factors.
      SIGNIFICANCE: We report proteomic changes as a result of genetic perturbation of
      JAZ7, and the contribution of JAZ7 in plant immunity. Specifically, the
      similarity between the proteomes of a JAZ7 knockout mutant and the wild type
      plants confirmed the functional redundancy of JAZs. In contrast, JAZ7
      overexpression plants were much different, and proteomic analysis of the JAZ7
      overexpression plants under Pst DC3000 infection revealed that JAZ7 may regulate
      plant immunity via ROS modulation, energy balance and glucosinolate biosynthesis.
      Multiple variate analysis for this two-factor proteomics experiment suggests that
      protein abundance is determined by genotype, environment and the interaction
      between them.

PMID- 29325991
TI  - Bothrops jararaca accessory venom gland is an ancillary source of toxins to the
      snake.
AB  - : In Viperidae snakes, it has been attributed to the main venom gland, a
      component of the venom gland apparatus, the function of synthesizing all venom
      toxins and storing them inside a basal-central lumen. However, the role of the
      accessory gland is still unknown. Here, we analyzed the proteome and the
      transcriptome of the accessory gland during venom production and secretion cycle.
      We showed that the accessory gland expresses and synthesizes toxins that are
      similar to those produced by the main venom gland such as C-type lectin/C-type
      lectin-like proteins, metalloproteinase, phospholipase A2, cysteine rich
      secretory protein, nerve growth factor, vascular endothelial growth factor,
      serine proteinase, and l-amino acid oxidase. Our data have shown that toxin
      synthesis in the accessory gland is asynchronous when compared to the same
      process in the venom gland. Moreover, this gland also expresses inhibitors of
      venom phospholipases A2 and metalloproteinases. Transcriptome analysis showed
      that the transcripts that correspond to toxins in the accessory gland have a good
      correlation to the main venom gland transcripts. Therefore, it is proposed that
      the accessory gland is an ancillary source of toxins to the snake, and provides
      inhibitors that could control venom toxicity (and integrity) during storage.
      SIGNIFICANCE: In this study, we propose that the accessory venom gland acts as an
      important ancillary source of toxins to the snake, in lieu of a depleted main
      venom gland, and provides inhibiting agents that control venom toxicity (and
      integrity) during its storage.

PMID- 29325992
TI  - Quantitative analysis of lipid debris accumulation caused by cuprizone induced
      myelin degradation in different CNS areas.
AB  - Degradation of myelin sheath is thought to be the cause of neurodegenerative
      diseases, such as multiple sclerosis (MS), but definitive agreement on the
      mechanism of how myelin is lost is currently lacking. Autoimmune initiation of MS
      has been recently questioned by proposing that the immune response is a
      consequence of oligodendrocyte degeneration. To study the process of myelin
      breakdown, we induced demyelination with cuprizone and applied coherent anti
      Stokes Raman scattering (CARS) microscopy, a non-destructive label-free method to
      image lipid structures in living tissue. We confirmed earlier results showing a
      brain region dependent myelin destructive effect of cuprizone. In addition, high
      resolution in situ CARS imaging revealed myelin debris forming lipid droplets
      alongwith myelinated axon fibers. Quantification of lipid debris with custom-made
      software for segmentation and three dimensional reconstruction revealed brain
      region dependent accumulation of lipid drops inversely correlated with the
      thickness of myelin sheaths. Finally, we confirmed that in situ CARS imaging is
      applicable to living human brain tissue in brain slices derived from a patient.
      Thus, CARS microscopy is potent tool for quantitative monitoring of myelin
      degradation in unprecedented spatiotemporal resolution during oligodendrocyte
      damage. We think that the accumulation of lipid drops around degrading myelin
      might be instrumental in triggering subsequent inflammatory processes.

PMID- 29325993
TI  - Serum haptoglobin in Chinese patients with Alzheimer's disease and mild cognitive
      impairment: A case-control study.
AB  - BACKGROUND: Serum level of Haptoglobin (Hp) maybe associated with Alzheimer's
      disease (AD) and mild cognitive impairment (MCI). OBJECTIVE: To investigate
      associations between serum Hp and AD, as well as between Hp and MCI. METHODS:
      Serum levels of Hp were measured and analyzed for 51 patients with AD, 139
      patients with MCI and their healthy controls matched with sex and age. All study
      subjects were from a survey among residents aged 60 years and over in a community
      located in the southwest suburb of Shanghai. RESULTS: Serum levels of Hp were
      observed significantly higher in AD and MCI cases than controls (both p <
      0.0001). A significant positive correlation was found between Hp and Activities
      of Daily Living (ADL) score (rs = 0.430, p = 0.007), as well as between Hp and
      Clinical Dementia Rating (CDR) score (rs = 0.359, p = 0.027) in all AD patients.
      According to the receiver operating characteristic (ROC) curve analysis, the
      optimal cut-off point for Hp was found to be 67.50 MUg/ml (sensitivity, 0.902;
      specificity, 0.745) in AD patients, and 44.76 MUg/ml (sensitivity, 0.986;
      specificity, 0.403) in MCI patients. CONCLUSION: Elevated serum levels of Hp were
      observed in AD and MCI patients than controls. In addition, Hp may correlate with
      the severity of AD.

PMID- 29325994
TI  - The effects of melatonin and curcumin on the expression of SIRT2, Bcl-2 and Bax
      in the hippocampus of adult rats.
AB  - OBJECTIVE: Though the mechanisms are not clearly understood, melatonin and
      curcumin have been reported to have neuroprotective effects. However, the
      mechanisms of neuroprotective effects of melatonin and curcumin in the brain are
      not clearly understood. In the current study, we investigated the effects of
      melatonin and curcumin treatments on oxidative stress parameters, the expression
      of SIRT2, Bcl-2 and Bax in the hippocampus. METHODS: A total of thirty adult (13
      months-old) male Wistar rats were divided into five groups: Control (1%
      ethanol:PBS), s.c. for 30 days), dimethyl sulfoxide (10%, s.c. for 30 days),
      Melatonin (10 mg/kg/day, s.c. for 30 days), Curcumin (30 mg/kg/day, i.p. for 30
      days) and Salermide (100 MUM, i.p. for 30 days). The levels of malondialdehyde
      (MDA) glutathione (GSH) were measured as oxidative stress parameters in the
      hippocampus. The expression levels of SIRT2, Bcl-2 and Bax proteins were tested
      by western blotting and the SIRT2 protein levels of the hippocampal region was
      measured by a sandwich ELISA method. RESULTS: Melatonin and curcumin
      significantly decreased MDA and SIRT2 expression in the hippocampus (p < 0.05).
      Accordingly, a significant increase in the GSH levels of curcumin-treated group
      and melatonin-treated group was observed. Melatonin, but not curcumin,
      significantly increased the Bcl-2 expression of the hippocampal region. There was
      a significant correlation between SIRT2 and MDA levels (p < 0.05). DISCUSSION: In
      conclusion, our results suggest that melatonin may increase cell survival in the
      hippocampus via decreasing oxidative stress and SIRT2 expression and increasing
      Bcl-2 expression.

PMID- 29325995
TI  - Acetylshikonin from Zicao attenuates cognitive impairment and hippocampus
      senescence in d-galactose-induced aging mouse model via upregulating the
      expression of SIRT1.
AB  - Zicao acts as a pleiotropic medicine in various diseases due to its particular
      pharmacological properties, including anti-inflammatory, anti-tumor, anti
      oxidative, and wound healing effects. However, few studies have focused on the
      function in neurodegenerative diseases of Zicao. In this study, we investigated
      the neuroprotective effect of Acetylshikonin (AS) from Zicao on the hippocampus
      of the d-galactose (d-gal)-induced sub-acute aging mouse model of Alzheimer's
      disease (AD). The aging model was established in male Kunming mice by
      subcutaneous injection of d-gal (150 mg/kg/d) for 60 days, and the mice were
      given AS (270, 540 and 1080 mg/kg/d) or distilled water intragastrically for 30
      days after 30 days of d-gal injection. The behavioral results test by Morris
      Water Maze (MWM) revealed that chronic AS treatment alleviated d-gal-induced
      learning and memory deficits compared with the d-gal-treated mice. In addition,
      AS also ameliorated the oxidative stress and neuroinflammation induced by d-gal
      through decreasing the level of interleukin-1beta (IL-1beta), tumor necrosis
      factor alpha (TNF-alpha), malondialdehyde (MDA) and enhancing the activity of the
      antioxidant enzymes superoxide dismutase (SOD). Moreover, western blot results
      showed that AS can up-regulate the expression of Sirtuin 1 (SIRT1) and inhibit d
      gal-induced activation of p53/p21 signaling pathway in the hippocampus of mice.
      These results suggest that AS can execute the prevention and treatment of d-gal
      induced brain aging by SIRT1/P53/P21 pathway.

PMID- 29325996
TI  - Direct-acting antiviral therapy for hepatitis C virus infection in the kidney
      transplant recipient.
AB  - Hepatitis C virus infection (HCV) is a common comorbidity in patients who have
      undergone kidney transplantation and is associated with increased morbidity and
      mortality compared with recipients who do not have chronic HCV infection. Because
      interferon-alpha-based therapies can precipitate acute rejection, they are
      relatively contraindicated after kidney transplantation. Thus, the majority of
      kidney transplant recipients with HCV remain untreated. There are now all-oral,
      interferon-free direct-acting antiviral therapies for HCV infection that are
      extremely effective and well tolerated in the general population. Recent reports
      in the literature demonstrate that direct-acting antiviral therapies effectively
      cured HCV in 406 of 418 kidney transplant recipients (97%); the majority were
      treated with sofosbuvir-based regimens. Smaller numbers of kidney transplant
      recipients have been treated with paritaprevir-ritonavir, ombitasvir and
      dasabuvir, elbasvir-grazoprevir, or glecaprevir-pibrentasvir with excellent
      success. Direct-acting antiviral therapies were well tolerated and did not
      increase the rate of acute rejection. The latest advances include approval of
      regimens that can treat patients with advanced allograft dysfunction (eGFR < 30
      ml/min per 1.73 m2) and "pan-genotypic" regimens that have activity against all 6
      major genotypes of HCV. This review summarizes what is known about the
      epidemiology of HCV infection in kidney transplant recipients, and presents the
      landscape of direct-acting antiviral therapies and areas in need of further
      investigation.

PMID- 29325997
TI  - Reduced cortical oxygenation predicts a progressive decline of renal function in
      patients with chronic kidney disease.
AB  - Renal tissue hypoxia is a final pathway in the development and progression of
      chronic kidney disease (CKD), but whether renal oxygenation predicts renal
      function decline in humans has not been proven. Therefore, we performed a
      prospective study and measured renal tissue oxygenation by blood oxygenation
      level-dependent magnetic resonance imaging (BOLD-MRI) in 112 patients with CKD,
      47 with hypertension without CKD, and 24 healthy control individuals. Images were
      analyzed with the twelve-layer concentric objects method that divided the renal
      parenchyma in 12 layers of equal thickness and reports the mean R2* value of each
      layer (a high R2* corresponds to low oxygenation), along with the change in R2*
      between layers called the R2* slope. Serum creatinine values were collected to
      calculate the yearly change in estimated glomerular function rate (MDRD eGFR).
      Follow up was three years. The change in eGFR in CKD, hypertensive and control
      individuals was -2.0, 0.5 and -0.2 ml/min/1.73m2/year, respectively. In
      multivariable regression analysis adjusted for age, sex, diabetes, RAS-blockers,
      eGFR, and proteinuria the yearly eGFR change correlated negatively with baseline
      24 hour proteinuria and the mean R2* value of the cortical layers, and positively
      with the R2* slope, but not with the other covariates. Patients with CKD and high
      outer R2* or a flat R2* slope were three times more likely to develop an adverse
      renal outcome (renal replacement therapy or over a 30% increase in serum
      creatinine). Thus, low cortical oxygenation is an independent predictor of renal
      function decline. This finding should stimulate studies exploring the therapeutic
      impact of improving renal oxygenation on renal disease progression.

PMID- 29325998
TI  - Use of mechanical cardiocompressor in uncontrolled donation after cardiac death.

PMID- 29325999
TI  - Current status of infectious endocarditis: New populations at risk, new
      diagnostic and therapeutic challenges.

PMID- 29326000
TI  - Epidemiology of tuberculosis in Spain. Results obtained by the National
      Epidemiological Surveillance Network in 2015.
AB  - The epidemiological surveillance data for tuberculosis in Spain in 2015 is
      analysed in this report. This information was gathered through cases reported to
      the Red Nacional de Vigilancia Epidemiologica [National Epidemiological
      Surveillance Network]. In addition, the update of the treatment of the cases
      reported in 2014 is included. The incidence rate of tuberculosis in 2015 was
      10.59 cases per 100,000 inhabitants, 10% less than in 2014. This decrease was
      mainly due to the sustained decreased trend of pulmonary tuberculosis rates, from
      other locations and in adults, while for cases of tuberculous meningitis and in
      children the decrease is less marked, with a tendency to stabilization. The
      percentage of cases born in other countries remains stable (approximately 30% of
      the total). Information on HIV status is available in 63% of cases, of which 7%
      were HIV-positive. Regarding the treatment results, 77% of the new lung cases
      confirmed by culture reported in 2014 had a satisfactory result, 6% died, and 11%
      did not have this information.

PMID- 29326001
TI  - Coxsackievirus and Type 1 Diabetes Mellitus: The Wolf's Footprints.
AB  - Enteroviruses are important environmental contributors to islet inflammation
      (insulitis) in type 1 diabetes mellitus (T1DM). A recent study characterized the
      proteomic alterations induced by Coxsackievirus type B (CVB) infection of human
      islets. This provides relevant information to decipher the words of the virus
      induced 'dialog' between beta cells and the immune system that leads to
      autoimmunity.

PMID- 29326002
TI  - Prevalence of adult Pompe disease in patients with proximal myopathic syndrome
      and undiagnosed muscle biopsy.
AB  - We examined patients with limb-girdle muscle weakness and/or hyper-CKaemia and
      undiagnosed muscle biopsy for late onset Pompe disease (LOPD). Patients with an
      inconclusive limb-girdle muscle weakness who presented at our neuromuscular
      centre between 2005 and 2015 with undiagnosed muscle biopsies were examined by
      dry blood spot testing (DBS) including determination of the enzyme activity of
      acid alpha-glucosidase (GAA). In the case of depressed enzyme activity,
      additional gene testing of the GAA gene was carried out. Of the 340 evaluated
      muscle biopsies, 69 patients fulfilled the inclusion criteria and were examined
      with DBS. Among those patients, 76% showed a limb-girdle muscle weakness and 14%
      showed a hyper-CKaemia. A diagnosis of LOPD could be established in the case of
      two patients (2.9%) with reduced GAA enzyme activity and proof of mutations in
      the GAA gene. One of the two patients presents in the muscle biopsy suggestive
      features of Pompe disease including vacuoles with positive acid phosphatase
      reaction. In summary, our results show that a muscle biopsy can be helpful in
      identifying LOPD patients, but vacuolation with glycogen storage can also be
      absent. An inconspicuous muscle biopsy does not rule out Pompe disease.
      Consequently, all patients with limb-girdle muscle weakness should be examined by
      DBS before conducting a muscle biopsy.

PMID- 29326003
TI  - The efficacy of infection prevention and control committees in Lesotho: A
      qualitative study.
AB  - BACKGROUND: The implementation of the core components of infection prevention and
      control (IPC) recommended by the World Health Organization faces severe
      challenges, particularly in developing countries. Given that hospital IPC
      committees in these countries are the key implementers of IPC, there is a need to
      evaluate their effectiveness. This study qualitatively evaluated the
      effectiveness of IPC committees in the southern African country of Lesotho with
      the aim of identifying themes for policy discourse on improving IPC practice in
      the country. METHODS: Data gathering was conducted through open interviews with
      purposefully selected key informant IPC committee members and relevant officials
      at the Ministry of Health, whereas data analysis was based on grounded theory.
      RESULTS: Despite their commitment, IPC committees were largely ineffective
      because of 5 major barriers, namely poor sense of competence, administrative
      constraints, inadequate financial support, role uncertainty, and negative staff
      attitudes. Poor IPC governance was found to be a central barrier to the
      effectiveness of IPC committees in Lesotho. CONCLUSIONS: The import of this study
      is that effective IPC governance is key to improving the IPC program in Lesotho.
      Effective leadership with the necessary competencies is needed to steer the IPC
      program in the country.

PMID- 29326004
TI  - Health care-associated infections in Iran: A national update for the year 2015.
AB  - BACKGROUND: A national surveillance system for health care-associated infections
      (HAIs) in Iran is relatively new, and an update on incidence and mortality rates
      can aid clinicians and stakeholders in development of new guidelines and
      imperative modifications to be made. METHODS: Data were extracted from the
      national HAIs surveillance software for more than 7 million hospitalizations
      during 2015. Data regarding age, gender, deaths, ward of admission, and
      microbiologic findings were collected and analyzed. RESULTS: From 491 hospitals,
      7,018,393 hospitalizations were reported during 2015; 82,950 patients had been
      diagnosed with at least 1 HAI, 6,355 of whom died (crude fatality rate, 7.7). Men
      comprised 51.4% of the patients. The incidence rate was calculated to be 1.18.
      Urinary tract infections and pneumonia were the most commonly reported infections
      (27.9% and 23.8%) and 33% of patients were older than age 65 years. Intensive
      care units had the highest incidence rates, followed by burn units with incidence
      rates close to 9. Highest percentages of deaths were reported among patients with
      an HAI in the intensive care unit (20.6%) and those with pneumonia (39.6%).
      CONCLUSION: Although the underreporting of HAIs hinders accurate calculation of
      incidence, the present study provides a general update. The results can help in
      modification of national guidelines and appropriate choice of antimicrobial
      agents in the management of HAIs.

PMID- 29326005
TI  - An anaerobic-aerobic sequential batch process with simultaneous methanogenesis
      and short-cut denitrification for the treatment of marine biofoulings.
AB  - Although combination of denitritation and methanogenesis for wastewater treatment
      has been widely investigated, an application of this technology to solid waste
      treatment has been rarely studied. This study investigated an anaerobic-aerobic
      batch system with simultaneous denitritation-methanogenesis as an effective
      treatment for marine biofoulings, which is a major source of intermittently
      discharged organic solid wastes. Preliminary NO2--exposed sludge was inoculated
      to achieve stable methanogenesis process without NO2- inhibition. Both high NH4+
      N removal of 99.5% and high NO2--N accumulation of 96.4% were achieved on average
      during the nitritation step. Sufficient CH4 recovery of 101 L-CH4 kg-COD-1 was
      achieved, indicating that the use of NO2--exposed sludge is effective to avoid
      NO2- inhibition on methanogenesis. Methanogenesis was the main COD utilization
      pathway when the substrate solubilization occurred actively, while denitritation
      was the main when solubilization was limited because of substrate shortage. The
      results showed a high COD removal efficiency of 96.0% and a relatively low
      nitrogen removal efficiency of 64.4%. Fitting equations were developed to
      optimize the effluent exchange ratio. The estimated results showed that the
      increase of effluent exchange ratio during the active solubilization period
      increased the nitrogen removal efficiency but decreased CH4 content in biogas. An
      appropriate effluent exchange ratio with high anaerobic effluent quality below
      approximately 120 mg-N L-1 as well as sufficient CH4 gas quality which can be
      used as fuel for gas engine generator was achieved by daily effluent exchange of
      80% during the first week and 5% during the subsequent 8 days.

PMID- 29326006
TI  - Digestate application in landfill bioreactors to remove nitrogen of old landfill
      leachate.
AB  - Anaerobic digestion of organics is one of the most used solution to gain
      renewable energy from waste and the final product, the digestate, still rich in
      putrescible components and nutrients, is mainly considered for reutilization (in
      land use) as a bio-fertilizer or a compost after its treatment. Alternative
      approaches are recommended in situations where conventional digestate management
      practices are not suitable. Aim of this study was to develop an alternative
      option to use digestate to enhance nitrified leachate treatment through a
      digestate layer in a landfill bioreactor. Two identical landfill columns (Ra and
      Rb) filled with the same solid digestate were set and nitrified leachate was used
      as influent. Ra ceased after 75 day's operation to get solid samples and
      calculate the C/N mass balance while Rb was operated for 132 days. Every two or
      three days, effluent from the columns were discarded and the columns were
      refilled with nitrified leachate (average N-NO3-concentration = 1,438 mg-N/L). N
      NO3- removal efficiency of 94.7% and N-NO3- removal capacity of 19.2 mg N-NO3
      /gTS-digestate were achieved after 75 days operation in Ra. Prolonging the
      operation to 132 days in Rb, N-NO3- removal efficiency and N-NO3- removal
      capacity were 72.5% and 33.1 mg N-NO3-/gTS-digestate, respectively. The
      experimental analysis of the process suggested that 85.4% of nitrate removal
      could be attributed to denitrification while the contribution percentage of
      adsorption was 14.6%. These results suggest that those solid digestates not for
      agricultural or land use, could be used in landfill bioreactors to remove the
      nitrogen from old landfill leachate.

PMID- 29326007
TI  - Direct recovery of boiler residue by combustion synthesis.
AB  - Boiler residue (BR) of thermal power plants is one of the important secondary
      sources for vanadium production. In this research, the aluminothermic self
      propagating high-temperature synthesis (SHS) was used for recovering the
      transition metals of BR for the first time. The effects of extra aluminum as
      reducing agent and flux to aluminum ratio (CaO/Al) were studied and the
      efficiency of recovery and presence of impurities were measured. Aluminothermic
      reduction of vanadium and other metals was carried out successfully by SHS
      without any foreign heat source. Vanadium, iron, and nickel principally were
      reduced and gone into metallic master alloy as SHS product. High levels of
      efficiency (>80%) were achieved and the results showed that SHS has a great
      potential to be an industrial process for BR recovery. SHS produced two useful
      products. Metallic master alloy and fused glass slag that is applicable for
      ceramic industries. SHS can also neutralize the environmental threats of BR by a
      one step process.

PMID- 29326008
TI  - [Acute neurological disease due to enterovirus: A review of clinical cases in a
      tertiary hospital in Andalusia after an outbreak in Catalonia].

PMID- 29326009
TI  - Is there sufficient evidence to repeal three decades of clinical research on
      chronic hepatitis C?

PMID- 29326010
TI  - Genomics of Corynebacterium striatum, an emerging multidrug-resistant pathogen of
      immunocompromised patients.
AB  - OBJECTIVES: Corynebacterium striatum is an emerging multidrug-resistant (MDR)
      pathogen of immunocompromised and chronically ill patients. The objective of
      these studies was to provide a detailed genomic analysis of disease-causing C.
      striatum and determine the genomic drivers of resistance and resistance-gene
      transmission. METHODS: A multi-institutional and prospective pathogen genomics
      programme flagged seven MDR C. striatum infections occurring close in time, and
      specifically in immunocompromised patients with underlying respiratory diseases.
      Whole genome sequencing was used to identify clonal relationships among strains,
      genetic causes of antimicrobial resistance, and their mobilization capacity.
      Matrix-assisted linear desorption/ionization-time-of-flight analyses of sequenced
      isolates provided curated content to improve rapid clinical identification in
      subsequent cases. RESULTS: Epidemiological and genomic analyses identified a
      related cluster of three out of seven C. striatum among lung transplant patients
      who had common procedures and exposures at an outlying institution. Genomic
      analyses further elucidated drivers of the MDR phenotypes, including resistance
      genes mobilized by IS3504 and ISCg9a-like insertion sequences. Seven mobilizable
      resistance genes were localized to a common chromosomal region bounded by
      unpaired insertion sequences, suggesting that a single recombination event could
      spread resistance to aminoglycosides, macrolides, lincosamides and tetracyclines
      to naive strains. CONCLUSION: In-depth genomic studies of MDR C. striatum reveal
      its capacity for clonal spread within and across healthcare institutions and
      identify novel vectors that can mobilize multiple forms of drug resistance,
      further complicating efforts to treat infections in immunocompromised
      populations.

PMID- 29326011
TI  - Neonatal intestinal colonization with extended-spectrum beta-lactamase-producing
      Enterobacteriaceae-a 5-year follow-up study.
AB  - OBJECTIVES: To analyse Klebsiella pneumoniae (KP) isolates from an outbreak of
      extended-spectrum beta-lactamase (ESBL)-producing KP and Escherichia coli (EC)
      among infants admitted to neonatal intensive care units and to determine the
      duration of the intestinal colonization. METHODS: We performed a prospective
      cohort study of intestinal ESBL-KP/ESBL-EC colonized neonates after a 5-month
      outbreak in two neonatal intensive care units. Whole genome sequencing,
      multilocus sequence typing, core genome multilocus sequence typing, pulsed-field
      electrophoresis and PCR for blaCTX-M were performed on the first isolates. Stool
      cultures were performed every second month after discharge until 2 years after
      discharge and at 5 years of age. The last positive samples were analysed with
      pulsed-field gel electrophoresis and PCR for blaCTX-M. The intestinal relative
      dominance of ESBL-producing Enterobacteriaceae was determined. RESULTS: Thirteen
      of 17 patients colonized with ESBL-KP/ESBL-EC survived. Isolates from 16 of 17
      patients were available for analysis and featured the same strain type of ESBL
      KP: sequence type 101. The strain had capsule type K29 and harboured blaCTX-M-15.
      The virulence genes irp1, irp2, iutA, kfu and mrk were detected in all isolates.
      The median length of colonization was 12.5 months (range, 5-68 months). After 2
      years, two of 13 patients were carriers of ESBL-KP and one of 13 of ESBL-EC. At 5
      years of age, one neonate was colonized with ESBL-EC. No infant experienced an
      ESBL-KP/EC-infection during follow-up. CONCLUSIONS: Two years after discharge,
      almost one fourth of the study participants were ESBL/KP-EC carriers. ESBL-KP
      sequence type 101 persisted in two of 13 children for 23 to 26 months. One
      patient was colonized with ESBL-EC at age 5 years.

PMID- 29326012
TI  - Stereotactic body radiotherapy (SBRT) for patients with locally advanced
      pancreatic cancer: A single center experience.
AB  - INTRODUCTION: Despite advances in treatment, notably in systemic therapy, the
      prognosis of pancreatic adenocarcinoma (PADC) remains dismal. Stereotactic body
      radiotherapy (SBRT) is an emerging tool in the complex management of PADC. We
      review outcomes of SBRT for PADC at our institution. METHODS: We reviewed
      patients treated with SBRT for either unresectable PADC or locally recurrent PADC
      after surgery. Treatment was delivered using a robotic radiosurgery system with
      respiratory tracking. The median prescribed dose was 30 Gy (30-35 Gy), delivered
      in 5-6 fractions. Toxicities were reported as per CTCAE v4.0. Survival was
      estimated using the Kaplan-Meier method. RESULTS: Between October 2010 and March
      2016, 21 patients were treated at our institution. The median follow-up was 7
      months (range: 1-28). The 1-year local control rate was 57%. The 1-year overall
      survival was 25% for locally advanced patients and 67% for those with local
      recurrences (p = 0.27). Eighty percent of cancer related deaths were due to
      metastatic progression. Five patients (24%) had Grade I-II gastrointestinal acute
      toxicity; one patient had fatal gastrointestinal bleeding 6 months after SBRT.
      CONCLUSION: In PADC, fractionated SBRT dose schedules near 30 Gy may strike the
      best balance of local control and bowel toxicity. More work is required to
      integrate pancreatic SBRT with modern systemic therapy.

PMID- 29326014
TI  - Ending tuberculosis calls for leaving no one behind.

PMID- 29326015
TI  - Ecchymosis and/or haematoma formation after prophylactic administration of
      subcutaneous enoxaparin in the abdomen or arm of the critically ill patient.
AB  - INTRODUCTION: Ecchymosis and/or haematoma are the most common adverse events
      after subcutaneous administration of low molecular weight heparin. There is no
      strong recommendation as to the puncture site. OBJECTIVE: To evaluate the adverse
      events, ecchymosis and/or haematoma after the administration of prophylactic
      subcutaneous enoxaparin in the abdomen vs the arm in the critically ill patient.
      METHODOLOGY: A randomised, two-arm clinical trial (injection in the abdomen vs
      the arm), performed between July 2014 and January 2017, in an 18-bed, polyvalent
      intensive care unit. Patients receiving prophylactic enoxaparin, admitted >72h,
      with no liver or haematological disorders, a body mass index (BMI) >18.5, not
      pregnant, of legal age and with no skin lesions which would impede assessment
      were included. We excluded patients who died or who were transferred to another
      hospital before completing the evaluation. We gathered demographic and clinical
      variables, and the onset of ecchymosis and/or haematomas at the injection site
      after 12, 24, 48 and 72hours. A descriptive analysis was undertaken, with group
      comparison and logistic regression. The study was approved by the ethics
      committee with the signed consent of patients/families. RESULTS: 301 cases (11
      excluded): 149 were injected in the abdomen vs 141 in the arm. There were no
      significant differences in demographic and clinical variables, BMI, enoxaparin
      dose or antiplatelet administration [ecchymosis, abdomen vs arm, n(%): 66(44) vs
      72(51), P=.25] [haematoma abdomen vs arm, n(%): 9(6) vs 14(10), P=.2].
      Statistical significance was found in the size of the haematomas after 72h: [area
      of haematoma (mm2) abdomen vs arm, median (IQR): 2(1-5.25) vs 20(5.25-156),
      P=.027]. CONCLUSIONS: In our patient cohort, prophylactic subcutaneous enoxaparin
      administered in the abdomen causes fewer haematomas after 72hours, than when
      administered in the arm. The incidence rate of ecchymosis and haematoma was lower
      than the published incidence in critically ill patients, although patients
      receiving anti-platelet agents present a higher risk of injury. No relationship
      was observed in relation to BMI.

PMID- 29326016
TI  - Synthesis of novel 6-substituted amino-9-(beta-d-ribofuranosyl)purine analogs and
      their bioactivities on human epithelial cancer cells.
AB  - New nucleoside derivatives with nitrogen substitution at the C-6 position were
      prepared and screened initially for their in vitro anticancer bioactivity against
      human epithelial cancer cells (liver Huh7, colon HCT116, breast MCF7) by the NCI
      sulforhodamine B assay. N6-(4-trifluoromethylphenyl)piperazine analog (27)
      exhibited promising cytotoxic activity. The compound 27 was more cytotoxic (IC50
      = 1-4 MUM) than 5-FU, fludarabine on Huh7, HCT116 and MCF7 cell lines. The most
      potent nucleosides (11, 13, 16, 18, 19, 21, 27, 28) were further screened for
      their cytotoxicity in hepatocellular cancer cell lines. The compound 27
      demonstrated the highest cytotoxic activity against Huh7, Mahlavu and FOCUS cells
      (IC50 = 1, 3 and 1 MUM respectively). Physicochemical properties, drug-likeness,
      and drug score profiles of the molecules showed that they are estimated to be
      orally bioavailable. The results pointed that the novel derivatives would be
      potential drug candidates.

PMID- 29326017
TI  - Small molecule immuno-oncology therapeutic agents.
AB  - Treatment of cancer by activation of an antitumor immune response is now a widely
      practiced and well-accepted approach to therapy. However, despite dramatic
      responses in some patients, the high proportion of unresponsive patients points
      to a considerable unmet medical need. Although antibody therapies have led the
      way, small molecule immuno-oncology agents are close behind. This perspective
      provides an overview of some of the many small molecule approaches being
      explored. It encompasses small molecule modulators of validated targets such as
      programed cell death 1 (PD-1) as well as novel approaches still to be proven
      clinically.

PMID- 29326013
TI  - A cluster of multidrug-resistant Mycobacterium tuberculosis among patients
      arriving in Europe from the Horn of Africa: a molecular epidemiological study.
AB  - BACKGROUND: The risk of tuberculosis outbreaks among people fleeing hardship for
      refuge in Europe is heightened. We describe the cross-border European response to
      an outbreak of multidrug-resistant tuberculosis among patients from the Horn of
      Africa and Sudan. METHODS: On April 29 and May 30, 2016, the Swiss and German
      National Mycobacterial Reference Laboratories independently triggered an outbreak
      investigation after four patients were diagnosed with multidrug-resistant
      tuberculosis. In this molecular epidemiological study, we prospectively defined
      outbreak cases with 24-locus mycobacterial interspersed repetitive unit-variable
      number tandem repeat (MIRU-VNTR) profiles; phenotypic resistance to isoniazid,
      rifampicin, ethambutol, pyrazinamide, and capreomycin; and corresponding drug
      resistance mutations. We whole-genome sequenced all Mycobacterium tuberculosis
      isolates and clustered them using a threshold of five single nucleotide
      polymorphisms (SNPs). We collated epidemiological data from host countries from
      the European Centre for Disease Prevention and Control. FINDINGS: Between Feb 12,
      2016, and April 19, 2017, 29 patients were diagnosed with multidrug-resistant
      tuberculosis in seven European countries. All originated from the Horn of Africa
      or Sudan, with all isolates two SNPs or fewer apart. 22 (76%) patients reported
      their travel routes, with clear spatiotemporal overlap between routes. We
      identified a further 29 MIRU-VNTR-linked cases from the Horn of Africa that
      predated the outbreak, but all were more than five SNPs from the outbreak.
      However all 58 isolates shared a capreomycin resistance-associated tlyA mutation.
      INTERPRETATION: Our data suggest that source cases are linked to an M
      tuberculosis clone circulating in northern Somalia or Djibouti and that
      transmission probably occurred en route before arrival in Europe. We hypothesise
      that the shared mutation of tlyA is a drug resistance mutation and phylogenetic
      marker, the first of its kind in M tuberculosis sensu stricto. FUNDING: The Swiss
      Federal Office of Public Health, the University of Zurich, the Wellcome Trust,
      National Institute for Health Research (NIHR) Oxford Biomedical Research Centre
      (BRC), the Medical Research Council, BELTA-TBnet, the European Union, the German
      Center for Infection Research, and Leibniz Science Campus Evolutionary Medicine
      of the Lung (EvoLUNG).

PMID- 29326018
TI  - Semisynthesis, cytotoxicity, antimalarial evaluation and structure-activity
      relationship of two series of triterpene derivatives.
AB  - In this report, we describe the semisynthesis of two series of ursolic and
      betulinic acid derivatives through designed by modifications at the C-3 and C-28
      positions and demonstrate their antimalarial activity against chloroquine
      resistant P. falciparum (W2 strain). Structural modifications at C-3 were more
      advantageous to antimalarial activity than simultaneous modifications at C-3 and
      C-28 positions. The ester derivative, 3beta-butanoyl betulinic acid (7b), was the
      most active compound (IC50 = 3.4 uM) and it did not exhibit cytotoxicity against
      VERO nor HepG2 cells (CC50 > 400 uM), showing selectivity towards parasites
      (selectivity index > 117.47). In combination with artemisinin, compound 7b showed
      an additive effect (CI = 1.14). While docking analysis showed a possible
      interaction of 7b with the Plasmodium protease PfSUB1, with an optimum binding
      affinity of -7.02 kcal/mol, the rather low inhibition displayed on a Bacillus
      licheniformis subtilisin A protease activity assay (IC50 = 93 uM) and the
      observed accumulation of ring forms together with a delay of appearance of
      trophozoites in vitro suggests that the main target of 3beta-butanoyl betulinic
      acid on Plasmodium may be related to other molecules and processes pertaining to
      the ring stage. Therefore, compound 7b is the most promising compound for further
      studies on antimalarial chemotherapy. The results obtained in this study provide
      suitable information about scaffolds to develop novel antimalarials from natural
      sources.

PMID- 29326019
TI  - Isolation of a peptide containing d-amino acid residues that inhibits the alpha
      helix-mediated p53-MDM2 interaction from a one-bead one-compound library.
AB  - alpha-Helix-mediated protein-protein interactions (PPIs) are important targets in
      biological research and drug development. Peptides containing d-amino acid
      residues are attractive molecules for inhibiting alpha-helix-mediated PPIs
      because of their wide surface area and high protease resistance. In this study, a
      peptide library was constructed using a one-bead one-compound format designed to
      isolate left-handed alpha-helical peptides, which are promising molecules as
      inhibitors of alpha-helix-mediated PPIs. Screening of the library against an
      alpha-helix-mediated PPI between MDM2 and p53 yielded an inhibitor of the PPI.
      Design and screening of the library, and biochemical and spectroscopic studies of
      the discovered peptide are presented.

PMID- 29326020
TI  - Cardiac Rupture in a Young Male Cocaine User.

PMID- 29326021
TI  - Similar clinical improvement and maintenance after rTMS at 5 Hz using a simple
      vs. complex protocol in Alzheimer's disease.
AB  - BRACKGROUND: Current treatments for Alzheimer's disease (AD) have a limited
      clinical response and methods, such as repetitive transcranial magnetic
      stimulation (rTMS), are being studied as possible treatments for the clinical
      symptoms with positive results. However, there is still seldom information on the
      type of rTMS protocols that deliver the best clinical improvement in AD.
      Objetive: To compare the clinical response between a simple stimulation protocol
      on the left dorsolateral prefrontal cortex (lDLPFC) against a complex protocol
      using six regions of interest. METHODS: 19 participants were randomized to
      receive any of the protocols. The analysis of repeated measures evaluated the
      change. RESULTS: Both protocols were equally proficient at improving cognitive
      function, behavior and functionality after 3 weeks of treatment, and the effects
      were maintained for 4 weeks more without treatment. CONCLUSION: We suggest rTMS
      on the lDLPFC could be enough to provide a clinical response, and the underlying
      mechanisms should be studied.

PMID- 29326023
TI  - Exploring quality of care and social inequalities related to type 2 diabetes in
      Hungary: Nationwide representative survey.
AB  - AIMS: The study aimed to launch a T2DM adult cohort that is representative of
      Hungary through a cross-sectional study, to produce the most important quality
      indicators for T2DM care, to describe social inequalities, and to estimate the
      absolute number of T2DM adult patients with uncontrolled HbA1c levels in Hungary.
      METHODS: A representative sample of the Hungarian T2DM adults (N=1280) was
      selected in 2016. GPs collected data on socio-demographic status by
      questionnaire, and on history and laboratory parameters from medical records. The
      process and outcome indicators used in the international monitoring practice were
      calculated. The socio-economic status influence was determined by multivariate
      logistic regression models. RESULTS: Target achievement was 61.66%, 53.48%, and
      54.00% for HbA1c, LDL-C, and blood pressure, respectively, in the studied sample
      (N=1176). In Hungary, 294,534 patients have above target HbA1c value out of
      495,801 T2DM adults. The education-dependent positive association with majority
      of process indicators was not reflected in HbA1c, LDL-C, and blood pressure
      target achievements. The risk of microvascular complications and requirement of
      insulin treatment were higher among less educated. CONCLUSIONS: According to our
      observations, the education-independent target achievement for HbA1c and LDL-C is
      similar as, for blood pressure is less effective in Hungary than in Europe.

PMID- 29326024
TI  - Aerodynamic Characteristics of Syllable and Sentence Productions in Normal
      Speakers.
AB  - BACKGROUND: Aerodynamic measures of subglottic air pressure (Ps) and airflow rate
      (AFR) are used to select behavioral voice therapy versus surgical treatment for
      voice disorders. However, these measures are usually taken during a series of
      syllables, which differs from conversational speech. Repeated syllables do not
      share the variation found in even simple sentences, and patients may use their
      best rather than typical voice unless specifically instructed otherwise. This
      study examined the potential differences in estimated Ps and AFR in syllable and
      sentence production and their effects on a measure of vocal efficiency in normal
      speakers. METHODS: Prospective study. Measures of estimated Ps, AFR, and
      aerodynamic vocal efficiency (AVE) were obtained from 19 female and four male
      speakers ages 22-44 years with no history of voice disorders. Subjects repeated a
      series of /pa/ syllables and a sentence at comfortable effort level into a face
      mask with a pressure-sensing tube between the lips. RESULTS: AVE varies as a
      function of the speech material in normal subjects. Ps measures were
      significantly higher for the sentence-production samples than for the syllable
      production samples. AFR was higher during sentence production than syllable
      production, but the difference was not statistically significant. AVE values were
      significantly higher for syllable versus sentence productions. CONCLUSIONS: The
      results suggest that subjects increase Ps and AFR in sentence compared with
      syllable production. Speaking task is a critical factor when considering measures
      of AVE, and this preliminary study provides a basis for further aerodynamic
      studies of patient populations.

PMID- 29326022
TI  - The effects of repetitive transcranial magnetic stimulation on eating behaviors
      and body weight in obesity: A randomized controlled study.
AB  - BACKGROUND: Although some studies have reported significant reductions in food
      cravings following repetitive transcranial magnetic stimulation (rTMS), none have
      examined changes in body weight. OBJECTIVE: We conducted 2-week randomized, sham
      controlled, single-blind, parallel-group trial to examine the effect of rTMS on
      body weight in obese patients. METHODS: Sixty obese patients (body mass index
      [BMI] >=25 kg/m2) aged between 18 and 65 years were recruited. A total of 4
      sessions of rTMS targeting the left dorsolateral prefrontal cortex (DLPFC) was
      provided over a period of 2 weeks, with a follow-up assessment conducted two
      weeks after treatment had finished. The primary outcome measure was weight change
      in kilograms from baseline to 4 weeks. Secondary endpoints included changes in
      anthropometric measures, cardiovascular risk factors, food intake, and appetite.
      RESULTS: Of the 60 volunteers, 57 completed the 4-week follow-up (29 in the TMS
      group and 28 in the sham treatment group). Participants in the rTMS group showed
      significantly greater weight loss from baseline following the 4 session of rTMS
      (p = 0.002). Consistent with weight loss, there was a significant reduction in
      BMI, fat mass and VAT at week 4 in the rTMS group compared with the control group
      (p < 0.05). After the 4 sessions of rTMS, the TMS group consumed fewer total
      kilocalories per day than the control group (p < 0.01). CONCLUSIONS: rTMS
      delivered to the left DLPFC was effective in decreasing food intake and
      facilitating weight loss in obese patients. The results of this study suggest
      that rTMS could be an effective treatment option for obesity. TRIAL REGISTRATION:
      Clinical trial registered with the Clinical Trials Tegistry at
      https://cris.nih.go.kr (KCT0001455).

PMID- 29326025
TI  - How Age and Frequency Impact the Thyroid Cartilages of Professional Singers.
AB  - OBJECTIVES/HYPOTHESIS: Young professional singers can easily reach very high
      pitches. In contrast, older singers often complain that they have to exert
      substantially more laryngopharyngeal force to reach the same high pitch compared
      with their earlier years. Various factors such as the property changes of the
      mucosa and ossification that impact the singing apparatus were suggested as
      explanations in the literature. The aim of this study was to analyze thyroid
      deformation-and thereby stiffness indirectly-during singing as a potential reason
      for this phenomenon. STUDY DESIGN: Prospective study. METHODS/DESIGN: We examined
      44 female professional singers. High-resolution computed tomography scans were
      performed during singing at the fundamental mean speaking frequency and the first
      and second octaves above it. Digital Imaging and Communications in Medicine scan
      data were rendered and visualized 3-dimensionally using MIMICS software. By
      superimposition of the different 3-dimensional images, different positions of the
      thyroid were visualized. The distance from the posterior border of the thyroid
      was measured in all the examinations. RESULTS: All laryngeal cartilages could be
      three-dimensionally visualized. The magnitude of the thyroidal deformation
      significantly depends on pitch and significantly correlates with age (r2 = 0.7, P
      < 0.001). CONCLUSIONS: The thyroid cartilage is flexible and its formability is
      especially important during singing. At higher pitches, the cartilage was more
      deformed. The larynx in older singers showed less thyroid cartilage deformation.

PMID- 29326027
TI  - Considering quantity and quality of life in metastatic castration-naive prostate
      cancer.

PMID- 29326026
TI  - Treatment Outcomes of Bilateral Medialization Thyroplasty for Presbylaryngis.
AB  - BACKGROUND: Presbylaryngis is a common cause of dysphonia in elderly patients.
      Type I thyroplasty serves to improve glottic closure and vocal quality by
      correcting bowing. Although unilateral and injection-based procedures are well
      characterized in the treatment of broadly defined glottic insufficiency, there
      are insufficient outcomes data for bilateral medialization thyroplasty in the
      treatment of presbylaryngis. The aim of this study was to review the change in
      measures of vocal quality before and after bilateral medialization thyroplasty
      for presbylaryngis. STUDY DESIGN: This is a retrospective case series. METHODS:
      The records of 21 patients with presbylaryngis undergoing bilateral medialization
      thyroplasty between 2007 and 2014 were reviewed. Implant materials included
      silastic (n = 17) and hydroxyapatite (n = 4). Preoperative and postoperative
      comparison of vocal function was conducted using Voice Handicap Index, maximum
      phonation time, auditory-perceptual severity ratings, and blinded paired
      comparison of Consensus Auditory-Perceptual Evaluation of Voice and Visual
      perceptual stroboscopic ratings. Paired sample t tests were used to assess all
      outcome measures. RESULTS: Significant improvements were found in Voice Handicap
      Index scores (P < 0.007), maximum phonation time (P < 0.03), Consensus Auditory
      Perceptual Evaluation of Voice (P < 0.04), and clinician rating of vocal quality
      (P < 0.0001). Blinded raters noted a significant improvement in audio (P < 0.05)
      and videostroboscopic (P < 0.003) samples after surgery. There were no operative
      complications observed, and median hospital stay was one night. CONCLUSIONS:
      Patients with presbylaryngis demonstrated significant improvement in both
      objective and subjective measures of vocal quality following bilateral
      medialization thyroplasty. These data suggest that medialization thyroplasty is a
      safe option that warrants consideration in the treatment of presbylaryngis.

PMID- 29326028
TI  - A new era for treatment development in HER2-positive breast cancer.

PMID- 29326029
TI  - Neoadjuvant treatment with trastuzumab and pertuzumab plus palbociclib and
      fulvestrant in HER2-positive, ER-positive breast cancer (NA-PHER2): an
      exploratory, open-label, phase 2 study.
AB  - BACKGROUND: In the neoadjuvant setting, blockade of HER2 plus use of an aromatase
      inhibitor in patients with HER2-positive and oestrogen receptor (ER)-positive
      breast cancer leads to a pathological complete response in 21% of patients.
      Convergence of HER2 and ER signals on RB1 suggests that a combined
      pharmacological intervention directed to these targets could be synergistic. To
      test this approach, we combined palbociclib to block RB1, fulvestrant to block
      ER, and trastuzumab with pertuzumab to block HER2 in patients with HER2-positive,
      ER-positive breast cancer. METHODS: NA-PHER2 is a multicohort, open-label,
      exploratory, phase 2 study done at seven sites in Italy. Patients were eligible
      for the first cohort if they had previously untreated, histologically confirmed,
      unilateral, invasive, HER2-positive, ER-positive breast cancer and were suitable
      for neoadjuvant therapy. Patients were treated every 3 weeks with intravenous
      trastuzumab (8 mg/kg loading dose followed by 6 mg/kg) and intravenous pertuzumab
      (840 mg loading dose in the first cycle and then at 420 mg) for six cycles plus
      oral palbociclib (125 mg once a day for 21 days in a 4-week cycle) and
      intramuscular fulvestrant (500 mg) every 4 weeks for five cycles. The coprimary
      endpoints were change from baseline in Ki67 expression at 2 weeks of treatment
      and at surgery (16 weeks after treatment) and changes in apoptosis from baseline
      to surgery. Secondary endpoints were clinical objective response (according to
      modified Response Evaluation Criteria in Solid Tumors) and pathological complete
      response. All patients who met eligibility criteria were assessed for the primary
      and secondary endpoints. All patients who received at least one cycle of therapy
      were assessed for safety. This trial is registered with ClinicalTrials.gov,
      number NCT02530424. The trial is ongoing and two further cohorts are being
      enrolled. FINDINGS: Between May 20, 2015, and Feb 8, 2016, we enrolled 36
      patients, of whom one was deemed ineligible for the study and five were found to
      be HER2-negative on retrospective analysis. Thus, 35 patients were included in
      safety analyses and 30 were assessed for the primary and secondary endpoints. At
      baseline, geometric mean Ki67 expression was 31.9 (SD 15.7), versus 4.3 (15.0) at
      week 2 (n=25; p<0.0001) and 12.1 (20.0) at time of surgery (n=22; p=0.013). The
      geometric mean for apoptosis was 1.2 (SD 0.3) at baseline versus 0.4 (0.4;
      p=0.019) at surgery. A clinical objective response immediately before surgery was
      achieved by 29 (97%; 95% CI 83-100) of 30 patients. At surgery, eight (27%; 95%
      CI 12-46) patients had a pathological complete response in breast and axillary
      nodes. The most frequent grade 3 adverse events were neutropenia (ten [29%]),
      diarrhoea (five [14%]), and stomatitis, increased alanine aminotransferase, and
      hypersensitivity reactions (one [3%] of each event). No grade 4 or serious
      adverse events were recorded in the study and there were no deaths.
      INTERPRETATION: The combination of palbociclib, fulvestrant, trastuzumab, and
      pertuzumab had a significant effect on the expression of Ki67 at 2 weeks and at
      surgery. Triple targeting of ER, HER2, and RB1 in HER2-positive and ER-positive
      breast cancer could be an effective chemotherapy-free treatment strategy. Further
      clinical testing and additional molecular characterisation is necessary, not only
      in hormone receptor-positive tumours but also in tumours without HER2
      amplification. FUNDING: Pfizer and Roche.

PMID- 29326030
TI  - Patient-reported outcomes following abiraterone acetate plus prednisone added to
      androgen deprivation therapy in patients with newly diagnosed metastatic
      castration-naive prostate cancer (LATITUDE): an international, randomised phase 3
      trial.
AB  - BACKGROUND: In the LATITUDE trial, addition of abiraterone acetate plus
      prednisone to androgen deprivation therapy (ADT) improved overall survival
      compared with placebos plus ADT in patients with newly diagnosed, high-risk,
      metastatic castration-naive prostate cancer. Understanding the effects of
      treatments on patient-reported outcomes (PROs) and health-related quality of life
      (HRQOL) is important for treatment decisions; therefore we aimed to analyse the
      effects of ADT plus abiraterone acetate and prednisone versus ADT plus placebos
      on PROs and HRQOL in patients in the LATITUDE study. METHODS: In the multicentre,
      international, randomised, phase 3 LATITUDE trial, eligible patients were aged 18
      years or older, had newly diagnosed, high-risk, metastatic castration-naive
      prostate cancer confirmed by bone scan (bone metastases) or by CT or MRI
      (visceral, soft tissue, or nodal metastases), and an Eastern Cooperative Oncology
      Group (ECOG) performance status score of 2 or less. Patients from 235 clinical
      sites in 34 countries were randomly assigned (1:1) following a country-by-country
      scheme done by permuted block randomisation (with two blocks) and stratified by
      the presence of visceral metastasis and ECOG performance status to receive ADT
      plus 1000 mg oral abiraterone acetate and 5 mg oral prednisone once daily or ADT
      plus placebos. Selection of ADT, chemical or surgical, was at the investigator's
      discretion. The co-primary endpoints of the trial, overall survival and
      radiographic progression-free survival, have been published. PRO data were
      collected directly on electronic tablet devices at the clinical sites during
      screening and before any other visit procedure on day 1 of cycles 1-3, monthly
      during cycles 4-13, and then every 2 months until the end of treatment, by use of
      the Brief Pain Inventory-Short Form (BPI-SF), Brief Fatigue Inventory (BFI),
      Functional Assessment of Cancer Therapy Prostate scale (FACT-P), and the EuroQol
      (EQ-5D-5L) questionnaires. PRO analyses were an exploratory endpoint. Analyses
      were by intention-to-treat. Results from the first pre-planned interim analysis
      (Oct 31, 2016), are presented here. This ongoing study is registered with
      Clinicaltrials.gov, number NCT01715285. FINDINGS: Between Feb 12, 2013, and Dec
      11, 2014, 1199 patients were randomly assigned: 597 to ADT plus abiraterone
      acetate and prednisone and 602 to ADT plus placebos. Median follow-up was 30.9
      months (IQR 21.2-33.2) in the ADT plus abiraterone acetate and prednisone group
      versus 29.7 months (1.4-43.5; 16.1-31.3) in the ADT plus placebos group. Median
      time to worst pain intensity progression assessed by the BPI-SF score was not
      reached in either group (ADT plus abiraterone acetate and prednisone, not reached
      [95% CI not reached to not reached]; 25th percentile 11.07 months [95% CI 9.23
      18.43]; ADT plus placebos group, not reached [95% CI not reached to not reached];
      25th percentile 5.62 [95% CI 4.63-7.39]; hazard ratio [HR] 0.63 [95% CI 0.52
      0.77]; p<0.0001). Median time to worst fatigue intensity was not reached in
      either the ADT plus abiraterone acetate and prednisone group (not reached [95% CI
      not reached to not reached]; 25th percentile 18.4 months [95% CI 12.9-27.7]) or
      the ADT plus placebos group (not reached [95% CI not reached to not reached];
      25th percentile 6.5 months [95% CI 5.6-9.2]; HR 0.65 [95% CI 0.53-0.81],
      p=0.0001). Median time to deterioration of functional status assessed by the FACT
      P total score scale was 12.9 months (95% CI 9.0-16.6) in the ADT plus abiraterone
      acetate and prednisone group versus 8.3 months (7.4-11.1) in the ADT plus
      placebos group (HR 0.85 [95% CI 0.74-0.99]; p=0.032). INTERPRETATION: The
      addition of abiraterone acetate plus prednisone to ADT in patients with newly
      diagnosed, high-risk metastatic castration-naive prostate cancer improved overall
      PROs by consistently showing a clinical benefit in the progression of pain,
      prostate cancer symptoms, fatigue, functional decline, and overall HRQOL.
      FUNDING: Janssen Research & Development.

PMID- 29326031
TI  - Depressive symptoms and poorer performance on the Stroop Task are associated with
      weight gain.
AB  - OBJECTIVE: Executive function impairments and depression are associated with
      obesity but whether they predict weight gain is unclear. METHODS: Forty-six
      individuals (35m, 37+/-10y) completed the Stroop Task, Iowa Gambling Task (IGT),
      Wisconsin Card Sorting Task (WCST), Inventory for Depressive Symptomatology (IDS
      SR), Physical Anhedonia Scale (PAS), and Perceived Stress Scale (PSS). Body
      composition (DXA) and fasting glucose were also measured. Data from return visits
      were used to assess changes in weight. RESULTS: Poorer Stroop and WCST
      performance associated with higher BMI whereas poorer IGT and WCST performance
      associated with higher body fat (%; all p's<=0.05). Stroop interference (p=0.04;
      p=0.05) and IDS-SR (p=0.06; p=0.02) associated with increased BMI and weight gain
      (%/yr). In a multivariate linear model Stroop interference (beta=0.40, p<0.01;
      beta=0.35, p<0.01) and IDS-SR (beta=0.38, p<0.01; beta=0.37, p<0.01)
      independently predicted increased BMI and weight gain (%/yr) even after
      controlling for baseline weight and glucose levels. CONCLUSIONS: Poorer response
      inhibition and depressive symptoms, but not glucose levels, predicted weight
      gain. Evaluating neurocognitive and mood deficits could improve current treatment
      strategies for weight loss. Clinical Trial Registration Numbers NCT00523627,
      NCT00342732, NCT01224704. clinicaltrials.gov.

PMID- 29326032
TI  - The anxiolytic effect of Juniperus virginiana L. essential oil and determination
      of its active constituents.
AB  - Essential oil from Juniperus virginiana L. (eastern red cedarwood essential oil,
      CWO) has been used to relax mind and enhance comfort for medical purposes. Few
      reports showed its effect on anxiety behaviors in animal models. The present
      study investigated the anxiolytic effect of CWO using two anxiety tests in mice,
      then determined the major active constituents, examined the change of
      neurotransmitters after intraperitoneal (i.p.) administration. Analysis using
      GC/MS revealed that the CWO contained (-)-alpha-cedrene (28.11%), (+)-beta
      cedrene (7.81%), (-)-thujopsene (17.71%) and (+)-cedrol (24.58%). CWO at 400
      800mg/kg increased the percentage of open arm entries and the percentage of the
      time spent in open arms in the elevated plus maze (EPM), suggesting that the oil
      has anxiolytic effect. However, it didn't show anxiolytic effect in the light
      dark box (LDB) test. Tests of the cedrene did not show anxiolytic effect in
      either test, but rather induced anxiety-related behaviors and inhibited the
      locomotor activity in EPM and LDB. Cedrol produced significant anxiolytic effect
      in both EPM and LDB tests at 400-1600mg/kg and 800-1600mg/kg, respectively. A
      more significant increase in locomotor activity was observed in cedrol at 200
      1600mg/kg administration than CWO. CWO increased the 5-hydroxytryptamine (5-HT)
      concentration at 800mg/kg, whereas it didn't affect the dopamine (DA)
      concentration. Cedrol significantly reduced the DA level at 100-200mg/kg and
      elevated the 5-HT level at 1200-1600mg/kg. Moreover, it changed the ratio of 5
      hydroxyindoleacetic acid/5-HT and 3, 4-dihydroxyphenyl acetic acid/DA at 1200
      1600mg/kg. CWO and cedrol, in particular might act in an anxiolytic effect
      through the 5-HTnergic and DAnergic pathways.

PMID- 29326033
TI  - The contribution of gender differences in motor, behavioral and cognitive
      features to functional capacity, independence and quality of life in patients
      with Huntington's disease.
AB  - INTRODUCTION: Huntington's disease (HD) is a neurodegenerative autosomal dominant
      disorder affecting patients' motor, behavioral and cognitive domains leading to
      total dependency for activities of daily life. This study compares whether gender
      differences in motor, cognitive and behavioral symptoms affect function and how
      functional impairment affects quality of life (QoL). METHODS: We recruited 2191
      subjects from the REGISTRY data base that provides personal data, HD age of
      onset, visit date, CAG mutation size, UHDRS and TFC scores from at least one
      visit. For 1166 participants SF-36 was also available. We calculated Spearman
      coefficients for correlations between particular symptomatic domains and
      functional scales, Fisher z-transform was used to test whether differences in
      correlations between genders were statistically significant. Simultaneous linear
      regression with least-square fit method was used to determine for how much
      variability in functional scales the particular symptomatic domains are
      responsible. ANOVA was used to look for QoL differences between TFC-stage based
      groups. Baseline statistics showed no significant differences between genders.
      RESULTS: Motor, cognitive and behavioral domains contributed significantly to
      function and independence. The motor domain contributed most followed by the
      cognitive and to a lesser degree by the behavioral domain. Motor symptoms
      correlated more with functional ability and influenced function variability more
      in women than in men. The decline in functional abilities correlated
      significantly with QoL decline. CONCLUSION: Motor symptoms have highest impact on
      function in HD, moreover these symptoms affect female function and independence
      more than males. Results indicate that symptomatic treatment targeting motor
      symptoms is needed to improve HD function and QoL.

PMID- 29326034
TI  - Hypoglycemia-induced parkinsonism with vasogenic basal ganglia lesion.

PMID- 29326035
TI  - Myoclonus in the elderly: A retrospective analysis of clinical and
      electrophysiological characteristics of patients referred to an electrophysiology
      laboratory.
AB  - BACKGROUND AND OBJECTIVE: Late-onset myoclonus in the elderly is mainly related
      to dementia or systemic disease. In this report, we aimed to investigate the
      clinical and electrophysiological features of patients with late-onset myoclonus.
      PATIENTS AND METHOD: We retrospectively assessed the medical records of patients
      who were referred to our electromyography laboratory. From these records, we
      included all patients who had myoclonus which started after the age of 60 years
      and in whom it was confirmed by polymyography. Demographic, clinical and
      electrophysiological findings were retrieved from the medical records. RESULTS:
      There were 63 patients with myoclonus. Types of myoclonus were spinal segmental
      (n = 2), cortical (n = 25) and probable cortico-subcortical involving upper
      extremities (n = 36). The latter two types displayed reflex sensitivity. Four
      patients (one with multifocal cortical myoclonus and others with probable cortico
      subcortical myoclonus) were diagnosed with probable CJD. Other diagnoses were
      Parkinsons's disease, Parkinson-plus or dementia syndromes, vascular
      parkinsonism, polyneuropathy, Celiac disease and post-hypoxic encephalopathy.
      Eleven patients did not have a specific diagnosis. CONCLUSIONS: Myoclonus in our
      cohort was mostly associated with parkinsonism. Cortical myoclonus is not rare in
      the elderly age group. Myoclonus in polyneuropathy is irregular, tremor-like with
      electrophysiological characteristics similar to the cortical subtype.

PMID- 29326036
TI  - Exploring young mothers' experiences with postpartum contraception in Ottawa:
      results from a multimethods qualitative study.
AB  - OBJECTIVES: Postpartum contraception plays a significant role in reducing
      subsequent pregnancy. However, young mothers in Ottawa, the capital of Canada,
      face various barriers when trying to access contraception after delivery. Through
      this project, we aimed to explore these barriers and understand the decision
      making processes of young mothers surrounding postpartum contraception. STUDY
      DESIGN: We conducted 10 semistructured in-depth interviews with young mothers
      living in Ottawa who had experienced a subsequent pregnancy within 24months of
      their first childbirth. In addition, we interviewed 10 key informants who work
      with teenage mothers. We audio-recorded and transcribed all interviews and
      analyzed them using inductive and deductive techniques. We used ATLAS.ti software
      to manage our data. RESULTS: Both young mothers and key informants report that
      teen mothers in Ottawa often do not use postpartum contraception or
      inconsistently use their chosen contraceptive method. Many factors, including
      cost, personal beliefs, personal priorities and knowledge, influence young
      mothers' decision making surrounding contraception. CONCLUSIONS: Our study
      suggests that when young mothers do not use postpartum contraception, the reasons
      are complex; for some, this is a choice, and for others, this is the result of
      systems-level, service delivery and information barriers. Supporting policies to
      ensure that a full range of contraceptive methods are available and affordable
      and developing educational programs in Ottawa that are sex-positive and
      nonjudgmental appear warranted. IMPLICATIONS: Ensuring that a full method mix,
      including contraceptive implants, is available to and affordable for young
      mothers in Ottawa could meet significant needs. Addressing existing systems
      level, service delivery and information barriers through supporting evidence
      based policies and sex-positive and nonjudgmental educational programs appears
      warranted.

PMID- 29326037
TI  - Experimental uptake and depuration of paralytic shellfish toxins in Southern Rock
      Lobster, Jasus edwardsii.
AB  - In October 2012, paralytic shellfish toxins (PST) were detected in the
      hepatopancreas of Southern Rock Lobsters (Jasus edwardsii) collected from the
      east coast of Tasmania, Australia. This resulted in the first commercial closure
      in Australia for this species. Questions were raised on how the toxins were
      transferred to the lobsters, how long the toxins would persist, whether PST
      contaminated hepatopancreas posed a risk to human health, and what management
      strategies could be applied. The aim of this study was to investigate whether PST
      contaminated mussels are a potential vector enabling toxin accumulation in J.
      edwardsii and to collect information on toxin uptake, distribution and depuration
      rates and toxin profiles under controlled experimental settings. Lobsters were
      fed mussels naturally contaminated with PST for a period of 28 days in an
      experimental setting; following this, lobsters were allocated to either fed or
      starved treatment groups. PST were not detected in the tail tissue of lobsters at
      any stage of the experiment. Lobster hepatopancreas contained mean levels of 2.4
      mg STX.2HCl eq/kg after 28 days of uptake, although substantial variability in
      total toxicity was observed. The PST profile of the hepatopancreas was similar to
      that of the contaminated mussels used as feed. Significant differences were noted
      in the PST depuration rates between fed and starved treatment groups. The daily
      depuration rate for total PST was estimated to be 0.019 and 0.013 mg STX.2HCl
      eq/kg for the fed and starved treatment groups respectively using a constant-rate
      decay model. After 42 days of depuration, total PST (STX equivalents) levels in
      the hepatopancreas of all lobsters were below 0.8 mg STX.2HCl eq/kg, which
      represents the regulatory level applied to bivalves. This result indicates that
      long-term holding to depurate PST may potentially be used as a risk management
      tool.

PMID- 29326038
TI  - A qualitative meta-synthesis of emergency department staff experiences of
      violence and aggression.
AB  - INTRODUCTION: Patient and visitor violence or aggression against healthcare
      workers in the Emergency Department (ED) is a significant issue worldwide. This
      review synthesises existing qualitative studies exploring the first-hand
      experiences of staff working in the ED to provide insight into preventing this
      issue. METHOD: A meta-ethnographic approach was used to review papers. RESULTS:
      Four concepts were identified: 'The inevitability of violence and aggression';
      'Staff judgments about why they face violence and aggression'; 'Managing in
      isolation'; and 'Wounded heroes'. DISCUSSION: Staff resigned themselves to the
      inevitability of violence and aggression, doing this due to a perceived lack of
      support from the organisation. Staff made judgements about the reasons for
      violent incidents which impacted on how they coped and subsequently tolerated the
      aggressor. Staff often felt isolated when managing violence and aggression. Key
      recommendations included: Staff training in understanding violence and aggression
      and clinical supervision. CONCLUSION: Violence and aggression in the ED can often
      be an overwhelming yet inevitable experience for staff. A strong organisational
      commitment to reducing violence and aggression is imperative.

PMID- 29326039
TI  - A descriptive study of registered nurses' application of the triage scale
      RETTS(c); a Swedish reliability study.
AB  - BACKGROUND: From a patient safety perspective, it is of great importance that
      decision support systems such as triage scales are evidence based. In the most
      recent national survey, the majority of Swedish Emergency Departments (EDs) apply
      the Swedish triage scale known as the Medical Emergency Triage Treatment Scale
      (METTS), subsequently renamed the Rapid Emergency Triage Treatment Scale
      (RETTS(c)). Despite national widespread implementation, there has been limited
      research on METTS/RETTS(c). AIM: To determine the reliability of application by
      registered nurses of the RETTS(c) triage scale in two Swedish emergency
      departments. METHODS: In this prospective, cross-sectional study at two EDs, 46
      written patient scenarios were triaged by 28 registered nurses (RNs). Data were
      analysed with descriptive statistics and Fleiss kappa (kappa). RESULTS: The RNs
      allocated 1281 final triage levels. There was concordance in seven (15%) of the
      scenarios, and dispersion over two or more triage levels in 39 (85%). Dispersion
      across the stable/unstable patient boundary was found in 21 (46%) scenarios.
      Fleiss kappa was 0.562, i.e. moderate agreement. CONCLUSION: The inability of the
      triage scale to distinguish between stable/unstable patients can lead to serious
      consequences from a patient safety perspective. No general pattern regarding
      concordance or dispersion was found.

PMID- 29326040
TI  - Downregulation of exocyst Sec10 accelerates kidney tubule cell recovery through
      enhanced cell migration.
AB  - Migration of surviving kidney tubule cells after sub-lethal injury, for example
      ischemia/reperfusion (I/R), plays a critical role in recovery. Exocytosis is
      known to be involved in cell migration, and a key component in exocytosis is the
      highly-conserved eight-protein exocyst complex. We investigated the expression of
      a central exocyst complex member, Sec10, in kidneys following I/R injury, as well
      as the role of Sec10 in wound healing following scratch injury of cultured Madin
      Darby canine kidney (MDCK) cells. Sec10 overexpression and knockdown (KD) in MDCK
      cells were used to investigate the speed of wound healing and the mechanisms
      underlying recovery. In mice, Sec10 decreased after I/R injury, and increased
      during the recovery period. In cell culture, Sec10 OE inhibited ruffle formation
      and wound healing, while Sec10 KD accelerated it. Sec10 OE cells had higher
      amounts of diacylglycerol kinase (DGK) gamma at the leading edge than did control
      cells. A DGK inhibitor reversed the inhibition of wound healing and ruffle
      formation in Sec10 OE cells. Conclusively, downregulation of Sec10 following I/R
      injury appears to accelerate recovery of kidney tubule cells through activated
      ruffle formation and enhanced cell migration.

PMID- 29326041
TI  - Role of the mRNA export factor Sus1 in oxidative stress tolerance in Candida
      albicans.
AB  - In eukaryotes, the nuclear export of mRNAs is essential for gene expression.
      However, little is known about the role of mRNA nuclear export in the important
      fungal pathogen, Candida albicans. In this study, we identified C. albicans Sus1,
      a nucleus-localized protein that is required for mRNA export. Interestingly, the
      sus1Delta/Delta displayed hyper-sensitivity to extracellular oxidative stress,
      enhanced ROS accumulation and severe oxidative stress-related cell death. More
      strikingly, although the mutant exhibited normal activation of the expression of
      oxidative stress response (OSR) genes, it had attenuated activity of ROS
      scavenging system, which may be attributed to the defect in OSR mRNA export in
      this mutant. In addition, the virulence of the sus1Delta/Delta was seriously
      attenuated. Taken together, our findings provide evidence that the mRNA export
      factor Sus1 plays an important role in oxidative stress tolerance and
      pathogenesis.

PMID- 29326042
TI  - Keratin 13 gene is epigenetically suppressed during transforming growth factor
      beta1-induced epithelial-mesenchymal transition in a human keratinocyte cell
      line.
AB  - Epithelial-mesenchymal transition (EMT) is a biological event in which epithelial
      cells lose their polarity and cell-cell adhesions and concomitantly acquire
      mesenchymal traits, and is thought to play an important role in pathological
      processes such as wound healing and cancer progression. In this study, we
      evaluated transforming growth factor (TGF)-beta1-treated human keratinocyte HaCaT
      cells as an in vitro model of EMT. HaCaT cells were changed into an elongated
      fibroblast-like morphology, which is indicative of EMT in response to TGF-beta1.
      Phalloidin staining demonstrated the formation of actin stress fibers in TGF
      beta1-treated cells. Quantitative RT-PCR analysis revealed that TGF-beta1
      increased the mRNA levels of EMT transcription factors (SNAI2, TWIST1, and ZEB1)
      and mesenchymal markers (CDH2, VIM, and FN1), while it decreased the transcripts
      of epithelial phenotypic genes (CLDN1, OCLN, KRT5, KRT15, KRT13, and TGM1).
      Furthermore, we found that KRT13 was drastically suppressed through the reduction
      of RNA polymerase II occupancy of its promoter, which was accompanied by a
      decrease in active histone marks (H3K4me3 and H3K27ac) and an increase in a
      repressive mark (H3K27me3) during EMT. These findings indicate that the TGF-beta1
      induced EMT program regulates a subset of epithelial and mesenchymal marker
      genes, and that KRT13 is transcriptionally suppressed through the modulation of
      the chromatin state at the KRT13 promoter in HaCaT cells.

PMID- 29326043
TI  - Upregulation of CDCA5 promotes gastric cancer malignant progression via
      influencing cyclin E1.
AB  - The cell division cycle associated 5(CDCA5) was reported to be associated with
      progression of several human cancers, however, its clinical significance and
      biological role still remain unknown in gastric cancer(GC). By analyzing The
      Cancer Genome Atlas(TCGA), we found CDCA5 was significantly upregulated in GC
      tissues compared to adjacent normal tissues. Tissue microarray(TMA) indicated
      upregulation of CDCA5 was significantly correlated with more advanced
      clinicopathological features, and acts as an independent risk factor for worse
      overall survival(OS) in GC patients. Moreover, silence of CDCA5 suppresses
      proliferation of GC cells by inducing G1-phase arrest via downregulating Cyclin
      E1(CCNE1). Our results demonstrate upregulation of CDCA5 promotes GC malignant
      progression, which may offer a potential prognostic and therapeutic strategy.

PMID- 29326044
TI  - Escherichia coli single-stranded DNA binding protein SSB promotes AlkB-mediated
      DNA dealkylation repair.
AB  - Repair of alkylation damage in DNA is essential for maintaining genome integrity.
      Escherichia coli (E.coli) protein AlkB removes various alkyl DNA adducts
      including N1-methyladenine (N1meA) and N3-methylcytosine (N3meC) by oxidative
      demethylation. Previous studies showed that AlkB preferentially removes N1meA and
      N3meC from single-stranded DNA (ssDNA). It can also remove N1meA and N3meC from
      double-stranded DNA by base-flipping. Notably, ssDNA produced during DNA
      replication and recombination, remains bound to E. coli single-stranded DNA
      binding protein SSB and it is not known whether AlkB can repair methyl adduct
      present in SSB-coated DNA. Here we have studied AlkB-mediated DNA repair using
      SSB-bound DNA as substrate. In vitro repair reaction revealed that AlkB could
      efficiently remove N3meC adducts inasmuch as DNA length is shorter than 20
      nucleotides. However, when longer N3meC-containing oligonuleotides were used as
      the substrate, efficiency of AlkB catalyzed reaction was abated compared to SSB
      bound DNA substrate of identical length. Truncated SSB containing only the DNA
      binding domain could also support the stimulation of AlkB activity, suggesting
      the importance of SSB-DNA interaction for AlkB function. Using 70-mer
      oligonucleotide containing single N3meC we demonstrate that SSB-AlkB interaction
      promotes faster repair of the methyl DNA adducts.

PMID- 29326046
TI  - Multi-tissue partial volume quantification in multi-contrast MRI using an
      optimised spectral unmixing approach.
AB  - Multi-tissue partial volume estimation in MRI images is investigated with a
      viewpoint related to spectral unmixing as used in hyperspectral imaging. The main
      contribution of this paper is twofold. It firstly proposes a theoretical analysis
      of the statistical optimality conditions of the proportion estimation problem,
      which in the context of multi-contrast MRI data acquisition allows to
      appropriately set the imaging sequence parameters. Secondly, an efficient
      proportion quantification algorithm based on the minimisation of a penalised
      least-square criterion incorporating a regularity constraint on the spatial
      distribution of the proportions is proposed. Furthermore, the resulting
      developments are discussed using empirical simulations. The practical usefulness
      of the spectral unmixing approach for partial volume quantification in MRI is
      illustrated through an application to food analysis on the proving of a Danish
      pastry.

PMID- 29326047
TI  - Periodontal status of tooth adjacent to implant with peri-implantitis.
AB  - OBJECTIVES: To evaluate the relationship between peri-implantitis and the
      periodontal health of the adjacent tooth, the periodontal status of the teeth
      adjacent and contralateral to the implants with and without peri-implantitis.
      METHODS: Fifty-three subjects with existing dental implants and chronic
      periodontitis were examined in this cross-sectional study. Seventy implants were
      categorized into peri-implantitis (n = 42) and healthy/mucositis (n = 28) groups.
      The periodontal and peri-implant status, including probing depth (PD), clinical
      attachment level (CAL), and gingival recession (GR) were measured at 6 sites
      around the implants and the teeth adjacent and contralateral to those implants.
      In total 560 sites of the 70 teeth/implant sets, the association between the
      periodontal status at the near and away sites of the teeth (according to implant)
      and the implant status (without/with peri-implantitis) was examined. RESULTS: A
      significantly different mean PD (5.01 +/- 1.69, 4.42 +/- 1.8, 3.55 +/- 0.88, and
      3.71 +/- 1.07 mm, p < 0.001) and CAL (6.02 +/- 2.36, 4.89 +/- 2.04, 4.35 +/-
      1.11, and 4.35 +/- 1.5 mm, p < 0.001) were noted at the near sites of the teeth
      adjacent to the implants with peri-implantitis when compared with the away sites
      of adjacent and contralateral teeth and the near sites of contralateral teeth.
      With generalized estimating equation (GEE), the presence of peri-implantitis
      (beta  = 1.041 mm, confidence interval = 0.646-1.435, and p < 0.001; beta  =
      0.857 mm, confidence interval = 0.279-1.434, and p < 0.004) and tooth location
      (beta  = 0.65 mm, confidence interval = 0.4-0.9, and p < 0.001; beta  = 0.682 mm,
      confidence interval = 0.34-1.024, and p < 0.001) were significantly associated
      with the values of the PD and CAL of the teeth. Moreover, the factor of examining
      sites (i.e. near and away sites of the tooth) was significantly associated with
      CAL (beta = 0.304 mm, confidence interval = 0.019-0.588, and p = 0.036) and GR
      (beta = 0.136 mm, confidence interval = 0.02-0.252, and p = 0.022). CONCLUSION:
      The existence of peri-implantitis, the tooth location, and the examining site are
      significantly associated with the periodontal measurements of the remaining
      teeth. CLINICAL SIGNIFICANCE: Peri-implant health is related to the periodontal
      health of the natural teeth close to the dental implant.

PMID- 29326045
TI  - ING5 inhibits cell proliferation and invasion in esophageal squamous cell
      carcinoma through regulation of the Akt/NF-kappaB/MMP-9 signaling pathway.
AB  - The inhibitor of growth 5 (ING5) is a new candidate tumor suppressor gene (TSG)
      of the ING family. So far, there have been many reports about its functions
      related to cancer development. However, the biological roles of ING5 in
      esophageal squamous cell carcinoma (ESCC) remain unclear. In the present study,
      we demonstrated that ING5 was lowly expressed in ESCC tissues and cell lines.
      Overexpression of ING5 inhibited ESCC cell proliferation and invasion in vitro as
      well as suppressed tumor growth and metastasis in vivo. We also found that
      overexpression of ING5 significantly decreased the levels of p-AKT, NF-kappaB and
      MMP-9 in ECA109 cells. Taken together, these findings demonstrated that ING5
      inhibited cell proliferation and invasion in ESCC through regulation of the
      Akt/NF-kappaB/MMP-9 signaling pathway. Thus, ING5 might be considered a promising
      target for ESCC treatment.

PMID- 29326049
TI  - Quantitative CT Assessment of Gynecomastia in the General Population and in
      Dialysis, Cirrhotic, and Obese Patients.
AB  - RATIONALE AND OBJECTIVES: Gynecomastia is the benign enlargement of the male
      breast because of proliferation of the glandular component. To date, there is no
      radiological definition of gynecomastia and no quantitative evaluation of breast
      glandular tissues in the general male population. The aims of this study were to
      supply radiological-based measurements of breast glandular tissue in the general
      male population, to quantitatively assess the prevalence of gynecomastia
      according to age by decades, and to evaluate associations between gynecomastia
      and obesity, cirrhosis, and dialysis. MATERIALS AND METHODS: This retrospective
      study included 506 men who presented to the emergency department following trauma
      and underwent chest-abdominal computed tomography. Also included were 45 patients
      undergoing hemodialysis and 50 patients with cirrhosis who underwent chest
      computed tomography. The incidence and size of gynecomastia for all the study
      population were calculated. RESULTS: Breast tissue diameters of 22 mm, 28 mm, and
      36 mm corresponded to 90th, 95th, and 97.5th cumulative percentiles of diameters
      in the general male population. Peaks of gynecomastia were shown in the ninth
      decade and in boys aged 13-14 years. Breast tissue diameter did not correlate
      with body mass index (r = -0.031). Patients undergoing hemodialysis and patients
      with cirrhosis had higher percentages (P < .0001) of breast tissue diameters
      above 22 mm, 28 mm, and 36 mm. CONCLUSIONS: Breast tissue diameter is a simple
      and reliable quantitative tool for the assessment of gynecomastia. This method
      provides the ability to determine the incidence of gynecomastia by age in the
      general population. Radiological gynecomastia should be defined as 22 mm, 28 mm,
      or 36 mm (90th, 95th, and 97.5th percentiles, respectively). Radiological
      gynecomastia is not associated with obesity, but is associated with cirrhosis and
      dialysis.

PMID- 29326048
TI  - Round robin study to evaluate the reconstructed human epidermis (RhE) model as an
      in vitro skin irritation test for detection of irritant activity in medical
      device extracts.

PMID- 29326050
TI  - A defined medium for Leishmania culture allows definition of essential amino
      acids.
AB  - Axenic culture of Leishmania is generally performed in rich, serum-supplemented
      media which sustain robust growth over multiple passages. The use of such
      undefined media, however, obscures proteomic analyses and confounds the study of
      metabolism. We have established a simple, defined culture medium that supports
      the sustained growth of promastigotes over multiple passages and which yields
      parasites that have similar infectivity to macrophages to parasites grown in a
      conventional semi-defined medium. We have exploited this medium to investigate
      the amino acid requirements of promastigotes in culture and have found that
      phenylalanine, tryptophan, arginine, leucine, lysine and valine are essential for
      viability in culture. Most of the 20 proteogenic amino acids promote growth of
      Leishmania promastigotes, with the exception of alanine, asparagine, and glycine.
      This defined medium will be useful for further studies of promastigote substrate
      requirements, and will facilitate future proteomic and metabolomic analyses.

PMID- 29326051
TI  - [Investigation methods to explore G protein-coupled receptor-regulated
      translatome].
AB  - With the advent of next-generation sequencing technologies, identifying the
      translatome, which includes genome-wide ribosome-associated mRNAs, provides new
      opportunities to define faithfully the protein repertoire of a cell, as opposed
      to transcriptomic approaches. In addition, the role that extracellular signals
      such as hormonal modulations could play on the translatome remains to be
      deciphered. In particular, the regulation of the translatome by G protein-coupled
      receptors (GPCR) is still poorly described, albeit the trophic role that many
      receptors of this family play in their target cells. Here, we provide an overview
      of the current methods that are used to study the translatome, applied to the
      GPCR receptor family.

PMID- 29326052
TI  - Sensitivity of airway cough-related afferents is influenced by female sex
      hormones.
AB  - Chronic hypersensitivity cough syndrome affects mainly postmenopausal women;
      however, the pathogenesis of cough hypersensitivity in this demographic is not
      entirely understood. The role of sex hormones in cough has never been studied in
      detail; however, sex hormones seem to play an important role in the lung health
      of women. Our study was aimed to analyse the effect of female sex hormones
      (oestrogen - E2 and progesterone - Pg) on cough sensitivity measured by
      inhalation of capsaicin in follicular and luteal phases of menstrual cycle,
      characterized by significantly different concentrations of sex hormones. These
      data were compared with a matched group of women taking oral contraceptives.
      Cough sensitivity to capsaicin increased in luteal phase in subjects with normal
      menstrual cycle, and this functional change was not present in group with
      contraceptive pills. The cough sensitivity correlates with the Pg/E2 ratio, and
      relative lack of oestrogen in luteal phase is associated with higher cough
      sensitivity to capsaicin.

PMID- 29326053
TI  - Molecular analysis of circulating tumors cells: Biomarkers beyond enumeration.
AB  - Advances in our molecular understanding of cancer biology have paved the way to
      an expanding compendium of molecularly-targeted therapies, accompanied by the
      urgent need for biomarkers that enable the precise selection of the most
      appropriate therapies for individual cancer patients. Circulating biomarkers such
      as circulating tumor cells (CTCs) are poised to fill this need, since they are
      "liquid biopsies" that can be performed non-invasively and serially, and may
      capture the spectrum of spatial and temporal tumor heterogeneity better than
      conventional tissue biopsies. Increasing evidence suggests that moving beyond the
      enumeration of CTCs towards more sophisticated molecular analyses can provide
      actionable data that may predict and potentially improve clinical outcomes. In
      this review, we discuss the potential of molecular CTC analyses to serve as
      prognostic and predictive biomarkers to guide cancer therapy and early cancer
      detection. As technologies to capture and analyze CTCs continue to increase in
      sophistication, we anticipate that the potential clinical applications of CTCs
      will grow exponentially in the coming years.

PMID- 29326054
TI  - Size-based separation methods of circulating tumor cells.
AB  - Circulating tumor cells (CTCs) originate from the primary tumor mass and enter
      into the peripheral bloodstream. Compared to other "liquid biopsy" portfolios
      such as exosome, circulating tumor DNA/RNA (ctDNA/RNA), CTCs have incomparable
      advantages in analyses of transcriptomics, proteomics, and signal colocalization.
      Hence, CTCs hold the key to understanding the biology of metastasis and play a
      vital role in cancer diagnosis, treatment monitoring, and prognosis. Size-based
      enrichment features are prominent in CTC isolation. It is a label-free, simple
      and fast method. Enriched CTCs remain unmodified and viable for a wide range of
      subsequent analyses. In this review, we comprehensively summarize the differences
      of size and deformability between CTCs and blood cells, which would facilitate
      the development of technologies of size-based CTC isolation. Then we review
      representative size-/deformability-based technologies available for CTC isolation
      and highlight the recent achievements in molecular analysis of isolated CTCs. To
      wrap up, we discuss the substantial challenges facing the field, and elaborate on
      prospects.

PMID- 29326056
TI  - Population ageing and cardiovascular health: the case of Greece.

PMID- 29326055
TI  - A retrospective biochemical, molecular, and neurocognitive review of Saudi
      patients with argininosuccinic aciduria.
AB  - A retrospective review was compiled of 54 patients with argininosuccinic aciduria
      who were either identified through the Saudi National Newborn Screening Program
      or diagnosed clinically from January 2000 to December 2015. The duration of
      follow-up is from 2 to 19 years. The majority of patients (65%) originated from
      the central province of Saudi Arabia. The mean patient age at review was 10 years
      (2-19 years), 92% received an early diagnosis (<28 days of age) and most were
      symptomatic at the time of the diagnosis (n = 34). Normal ammonia at diagnosis
      was reported in 30% of patients, who were detected under the newborn metabolic
      screen (n = 5/16). A very high rate of consanguinity was observed in our cohort
      (98%). Developmental delay was the most detectable long term neurocognitive
      consequence followed by seizure disorder; 90.7% (n = 49) and 62.9% (n = 34)
      respectively. As expected, the severe neonatal form was the major presentation.
      The most common variant identified in this cohort was the previously reported
      founder c.1060C > T; p.(Gln354*) nonsense mutation in the ASL gene. In addition,
      the frequency of hyperammonemia was higher in patients homozygous for c.1060C >
      T; p.(Gln354*) compared to the other mutations. Interestingly, frequent
      thrombocytosis with the mean level of 717 * 109/L (range = 457-1169 * 109/L) was
      observed in 96% of the patients with no clear explanation.

PMID- 29326058
TI  - Sleep architecture is altered in the reserpine-induced fibromyalgia model in
      ovariectomized rats.
AB  - Fibromyalgia (FM) is a musculoskeletal chronic pain syndrome with various
      concomitant symptoms like sleep disorders. FM patients are mainly women and
      menopause might play an important role in the altered processing of somatosensory
      information. Adverse effects and moderated efficacy of drugs promote treatment
      discontinuation by patients. Animal models of FM report pain and depression-like
      behaviors, but none of them have explored sleep disturbance as possible marker in
      the preclinic diagnostic. The aim of this study was to investigate alterations of
      the sleep architecture in the reserpine (RES)-induced FM model in ovarectomized
      (OVX) rats. The behavioral thresholds of nociceptive response in the experimental
      FM were analyzed in a first block using muscle pressure, tactile response and
      allodynia to cold stimulus. In a second block, the sleep-wake cycle was examined
      in a polysomnographic study. Groups (n = 8) consisted in: (a) no treatment, (b)
      RES vehicle, (c) RES alone, (d) RES + vehicle of fluoxetine (FLX, antidepressant
      reference drug), and (e) RES + FLX. Our results demonstrated that RES induced
      pain-related behavior (50-70%) in OVX rats and altered sleep architecture by the
      increase of total wake time (38%), diminution of the no-REM stage (SWS-I 33% and
      SWS-II 76%), and abolition of the REM sleep, effects that were partially reverted
      in the presence of FLX. In conclusion, our results support the face validity of
      the RES-induced pain-related behavior as FM model showing nociceptive behavioral
      responses associated to sleep alterations observed as symptoms in FM patients;
      thus, these evidences substantiate its usefulness to look for alternatives of
      treatment for FM symptoms.

PMID- 29326057
TI  - Antidepressant effects of focused ultrasound induced blood-brain-barrier opening.
AB  - In many cases, hippocampal neurogenesis appears to be a hallmark of
      antidepressant treatments. One novel technique for inducing this type of
      neurogenesis is using focused ultrasound waves, in conjunction with circulating
      microbubbles, to open the blood-brain-barrier. The present experiment aimed to
      test whether this technique has antidepressant effects in a rodent model. Rats
      were subjected to 1, 2 or 3 weekly treatments of magnetic resonance-guided
      focused ultrasound in order to open the blood-brain-barrier in the hippocampal
      region. Before and after treatments, animals went through modified forced swim
      tests. 1 week after the final treatment, animals that received 2 weekly
      treatments showed antidepressant-like effects on behavioural measures in
      comparison to untreated controls. This was not the case for animals that received
      1 or 3 weekly treatments. Effects had disappeared by 5 weeks following the first
      ultrasound treatment. These results suggest that focused ultrasound may be used
      for inducing short-term antidepressant effects.

PMID- 29326060
TI  - Ovulation is associated with the LH-dependent induction of pla2g4aa in zebrafish.
AB  - The effects of the preovulatory luteinizing hormone (LH) surge on the ovulatory
      process are mediated by prostaglandins (PGs), the synthesis of which involves
      prostaglandin synthetase and cytosolic phospholipase A2 (cPLA2). In our previous
      study, we systematically investigated the function of prostaglandin endoperoxide
      synthase (ptgs) genes on ovulation in zebrafish. However, the role of cPLA2 in
      ovulation was not determined in zebrafish. In this study, we investigated the
      function of cpla2alpha in PGs production and ovulation in periovulatory
      follicles. Our data showed that the expression of pla2g4aa increased during
      zebrafish folliculogenesis and the follicular layer was the primary region with
      expression of pla2g4aa. In addition, the expression of pla2g4aa was regulated by
      LH in vitro and in vivo. Furthermore, injection of AACOCF3, a specific inhibitor
      of cPLA2, significantly reduced ovarian PGs level and blocked hCG-induced
      ovulation. Collectively, these findings suggest that pla2g4aa is related to the
      ovulation process in zebrafish.

PMID- 29326059
TI  - Differential requirement of de novo Arc protein synthesis in the insular cortex
      and the amygdala for safe and aversive taste long-term memory formation.
AB  - Several immediate early genes products are known to be involved in the
      facilitation of structural and functional modifications at distinct synapses
      activated through experience. The IEG-encoded protein Arc (activity regulated
      cytoskeletal-associated protein) has been widely implicated in long-term memory
      formation and stabilization. In this study, we sought to evaluate a possible role
      for de novo Arc protein synthesis in the insular cortex (IC) and in the amygdala
      (AMY) during long-term taste memory formation. We found that acute inhibition of
      Arc protein synthesis through the infusion of antisense oligonucleotides
      administered in the IC before a novel taste presentation, affected consolidation
      of a safe taste memory trace (ST) but spared consolidation of conditioned taste
      aversion (CTA). Conversely, blocking Arc synthesis within the AMY impaired CTA
      consolidation but had no effect on ST long-term memory formation. Our results
      suggest that Arc-dependent plasticity during taste learning is required within
      distinct structures of the medial temporal lobe, depending on the emotional
      valence of the memory trace.

PMID- 29326061
TI  - Neuropathic pain in end-stage hip and knee osteoarthritis: differential
      associations with patient-reported pain at rest and pain on activity.
AB  - OBJECTIVE: We investigated whether pain at rest and pain on activity were
      differentially associated with neuropathic pain scores in individuals with end
      stage hip and knee OA. DESIGN: Study participants were 843 patients with hip or
      knee OA scheduled for total joint arthroplasty. In pre-surgery questionnaires,
      measures of socio-demographics, health status, medication use, neuropathic pain
      (painDETECT), pain at rest and pain on activity (WOMAC pain items), depression
      (HADS) and pain catastrophizing (PCS) were collected. Multivariable linear
      regression models were estimated for men and women separately to examine the
      association between neuropathic pain scores (outcome) and study measures, entered
      in blocks. RESULTS: Sample mean age was 65.1 years (SD: 9.6); 57.1% were women.
      Mean painDETECT scores were significantly higher (P <=? 0.001) for women (11.2 +/
      6.6 out of 38) than men (9.3 +/- 7.0), with 35.6% of women and 27.7% of men
      meeting cut-offs for possible or likely neuropathic pain. In the final regression
      model for women, the coefficients for both types of pain were statistically
      significant, although the coefficient for pain at rest was 1.6 times greater than
      that for pain on activity. For men, only pain at rest was significantly
      associated with neuropathic pain scores. CONCLUSIONS: Findings support that
      possible neuropathic pain is experienced by a notable proportion of patients with
      end-stage hip and knee OA and is more strongly associated with pain at rest than
      pain on activity, particularly in men. Clinical presentation of pain at rest may
      warrant more thorough evaluation for potential neuropathic pain and have
      implications for appropriate pain management.

PMID- 29326062
TI  - Functional effects of an interpenetrating polymer network on articular cartilage
      mechanical properties.
AB  - OBJECTIVE: Depletion of glycosaminoglycans (GAGs) and degradation of collagen
      network are early hallmarks of osteoarthritis (OA). Currently, there are no
      chondroprotective therapies that mitigate the loss of GAGs or effectively restore
      the collagen network. Recently, a novel polymeric cartilage supplement was
      described that forms a charged interpenetrating polymer network (IPN)
      reconstituting the hydrophilic properties of the extracellular matrix (ECM). To
      investigate the mechanism by which this hydrophilic IPN improves articular
      cartilage material properties, a finite element (FE) model is used to evaluate
      the IPN's effect on the fibrillar collagen network, nonfibrillar matrix, and
      interstitial fluid flow. METHODS: Bovine osteochondral plugs were degraded with
      chondroitinase ABC to selectively decrease GAG content. Samples were mechanically
      tested before and after IPN treatment using unconfined testing geometry and
      stress-relaxation protocol. Every measurement was modeled separately using a
      fibril-reinforced poroviscoelastic FE model. Measurement replication was achieved
      by optimizing the following model parameters: initial and strain-dependent fibril
      network modulus (Ef0, Efepsilon, respectively), nonfibrillar matrix modulus
      (Enf), initial permeability (k0) and strain-dependent permeability factor (M).
      RESULTS: Based on the FE model results, treatment of native and GAG depleted
      cartilage with the hydrophilic IPN increases the ECM stiffness and impedes fluid
      flow. The IPN did not alter the stiffness of fibrillary network. Cartilage
      permeability and the strain-dependent permeability factor decreased with
      increasing IPN w/v%. CONCLUSIONS: The IPN reconstitutes cartilage material
      properties primarily by augmenting the hydrophilic ECM. This reinforcement of the
      solid phase also affects the fluid phase reestablishing low permeability.

PMID- 29326063
TI  - Efficient purification of a highly active H-subunit of tyrosinase from Agaricus
      bisporus.
AB  - A highly-active tyrosinase (H subunit) isoform has been purified from a
      commercial crude extract of Agaricus bisporus by a specific, two step-hydrophobic
      chromatography cascade process based on the differential adsorption of the
      proteins from the extract to hydrophobic-functionalized supports. At first,
      commercial, crude tyrosinase from Agaricus bisporus (AbTyr) dissolved in aqueous
      media was added to octadecyl-Sepabeads matrix at 25  degrees C. Under these
      conditions, the support specifically adsorbed a protein with a molecular weight
      of 47 kDa which showed no tyrosinase activity. The known H subunit of tyrosinase
      from Agaricus bisporus (45 kDa, H-AbTyr) and another protein of 50 kDa were
      present in the supernatant. Sodium phosphate buffer was added to adjust the ionic
      strength of the solution up to 100 mM and Triton X-100 was added (final
      concentration of 0.07% v/v) to control the hydrophobicity effect for both
      proteins. This solution was offered again to fresh octadecyl-Sepabeads support,
      immobilizing selectively the H-AbTyr and leaving exclusively the 50 kDa protein
      as a pure sample in the supernatant. This tyrosinase isoform of 50 kDa was almost
      4-fold more active than the known H-TyrAb, with a specific tyrosinase activity of
      more than 38,000 U/mg.

PMID- 29326064
TI  - Selection of the Best of 2017 in Pulmonary Hypertension.

PMID- 29326065
TI  - Hydrogen sulfide supplement attenuates the apoptosis of retinal ganglion cells in
      experimental glaucoma.
AB  - Glaucoma is a group of neurodegenerative eye diseases characterized by
      progressive impairment of visual function due to loss of retinal ganglion cells
      (RGC). As hydrogen sulfide (H2S) was reported to play a role in the process of
      glaucomatous neuropathy and improve RGC survival in experimental glaucoma, the
      authors aimed to investigate the anti-apoptosis effect of H2S supplement in a rat
      glaucoma model, and further tried to explore the involved factors in the
      neuroprotection. A chronic ocular hypertension (COH) rat model induced by
      intracameral injection of cross-linking hydrogel was employed to simulate
      glaucoma and 288 rats were subjected to experimental procedures in the present
      study. After 4 weeks of sodium hydrosulfide (NaHS) administration following COH
      induction, the apoptosis of RGC isolated from experimented rats as well as
      apoptosis of neurons in ganglion cell layer (GCL), intrinsic apoptotic pathway
      activity, mitochondrial function, glial activation, NF-kappaB pathway activity,
      NADPH oxidase activity, autophagy activity and TNF-alpha level in retina were
      evaluated. The results showed that H2S supplement effectively attenuated the
      apoptosis of RGC in experimental glaucoma, and the neuroprotection by H2S might
      correlate with preservation of mitochondrial function, attenuation of oxidative
      stress, suppression of glial activation, inhibition of inflammatory pathways and
      downregulation of autophagy. Our study indicated that H2S supplement resulted in
      significant neuroprotection through attenuation of RGC apoptosis which might be
      linked with multiple factors in experimental glaucoma. The new therapeutic
      strategy might potentially contribute to benefit glaucoma treatment, which is
      worth further concerns.

PMID- 29326066
TI  - Novel everolimus-loaded nanocarriers for topical treatment of murine experimental
      autoimmune uveoretinitis (EAU).
AB  - In the present study, therapeutic effect of topically applied everolimus (EV)
      loaded methoxy-poly(ethylene-glycol)-hexyl substituted poly (lactic acid)
      (mPEGhexPLA) nanocarriers on experimental autoimmune uveoretinitis (EAU) were
      investigated. EAU was induced in B10.RIII mice via immunization with human
      interphotoreceptor retinoid-binding protein peptide 161-180 (hIRBPp161-180) in
      complete Freund's adjuvant. Everolimus-loaded mPEGhexPLA (EV/mPEGhexPLA)
      nanocarriers were prepared by using a solvent evaporation method. On days 12-21
      postimmunization (p.i.), the right eyes were treated five times daily either with
      10 MUl of 0.5% everolimus formulation or PBS (control). The EAU score of the eyes
      was determined histologically. On day 21 p.i., the peripheral immune responses
      were measured in serum, cervical lymph nodes (LN), and spleens via hIRBPp161-180
      specific serum antibodies, cytokine secretion (ELISA), lymphocyte proliferation,
      and FoxP3+ regulatory T cells (Treg; flow cytometry). Compared to the PBS-treated
      mice, unilateral topical everolimus treatment significantly reduced EAU severity
      in both eyes (p < .05). The treatment reduced the antigen (Ag)-specific hIRBPp161
      180-induced proliferation (p < .05), IL-2, IL-17, and IFN-gamma secretion from
      cells isolated from the left and right cervical LN (p < .05). Under everolimus
      treatment, IL-10 secretion and CD4+CD25+FoxP3+ Treg frequency from cervical LN
      were enhanced. The proliferative response and cytokine secretion as well as the
      frequency of splenic Treg were almost unchanged. Topical administration of an
      everolimus formulation improved EAU in both eyes. The effect might also be
      related to systemic immunosuppressive effects, as several systemic cellular
      immune responses were influenced.

PMID- 29326067
TI  - Transcutaneous vagus nerve stimulation (tVNS) enhances divergent thinking.
AB  - Creativity is one of the most important cognitive skills in our complex and fast
      changing world. Previous correlative evidence showed that gamma-aminobutyric acid
      (GABA) is involved in divergent but not convergent thinking. In the current
      study, a placebo/sham-controlled, randomized between-group design was used to
      test a causal relation between vagus nerve and creativity. We employed
      transcutaneous vagus nerve stimulation (tVNS), a novel non-invasive brain
      stimulation technique to stimulate afferent fibers of the vagus nerve and
      speculated to increase GABA levels, in 80 healthy young volunteers. Creative
      performance was assessed in terms of divergent thinking (Alternate Uses Task) and
      convergent thinking tasks (Remote Associates Test, Creative Problem Solving Task,
      Idea Selection Task). Results demonstrate active tVNS, compared to sham
      stimulation, enhanced divergent thinking. Bayesian analysis reported the data to
      be inconclusive regarding a possible effect of tVNS on convergent thinking.
      Therefore, our findings corroborate the idea that the vagus nerve is causally
      involved in creative performance. Even thought we did not directly measure GABA
      levels, our results suggest that GABA (likely to be increased in active tVNS
      condition) supports the ability to select among competing options in high
      selection demand (divergent thinking) but not in low selection demand (convergent
      thinking).

PMID- 29326068
TI  - Slime mould: The fundamental mechanisms of biological cognition.
AB  - The slime mould Physarum polycephalum has been used in developing unconventional
      computing devices for in which the slime mould played a role of a sensing,
      actuating, and computing device. These devices treated the slime mould as an
      active living substrate, yet it is a self-consistent living creature which
      evolved over millions of years and occupied most parts of the world, but in any
      case, that living entity did not own true cognition, just automated biochemical
      mechanisms. To "rehabilitate" slime mould from the rank of a purely living
      electronics element to a "creature of thoughts" we are analyzing the cognitive
      potential of P. polycephalum. We base our theory of minimal cognition of the
      slime mould on a bottom-up approach, from the biological and biophysical nature
      of the slime mould and its regulatory systems using frameworks such as Lyon's
      biogenic cognition, Muller, di Primio-Lengelers modifiable pathways, Bateson's
      "patterns that connect" framework, Maturana's autopoietic network, or proto
      consciousness and Morgan's Canon.

PMID- 29326069
TI  - Positive correlation between rat brain glutamate concentrations and mitochondrial
      2-oxoglutarate dehydrogenase activity.
AB  - Glutamate is a key metabolite and major excitatory neurotransmitter, degraded
      through transformation to 2-oxoglutarate which is further catabolized by 2
      oxoglutarate dehydrogenase complex (OGDHC). Both the glutamate excitotoxicity and
      impaired OGDHC activity are hallmarks of neurodegeneration. This work quantifies
      a relationship between the brain OGDHC activity and glutamate levels, assessing
      its diagnostic value to characterize (patho)physiology. A moderate to strong
      positive correlation of the two parameters determined under varied physiological
      settings (brain regions, seasons, gender, pregnancy, rat line), is revealed.
      Mitochondrial impairment (OGDHC inhibition or acute hypobaric hypoxia) decreases
      the interdependence, even when the parameter means do not change significantly.
      Compared to the cortex, the cerebellum exhibits a lower inter-individual
      glutamate variation and a weaker glutamate-OGDHC interdependence. Specific
      metabolism of the brain regions is also characterized by a positive correlation
      between glutamate and gamma-aminobutyric acid (GABA) concentrations in the cortex
      but not in the cerebellum. In contrast, a strong positive correlation between
      glutamate and glutamine is present in both the cortex and cerebellum. The
      differences in metabolic correlations are in line with transcriptomics data which
      suggest that glutamate distribution between competitive pathways contributes to
      the brain-region-specific features of the interdependences of glutamate and OGDHC
      or GABA.

PMID- 29326070
TI  - Enhanced protein identification using graphite-modified MALDI plates for offline
      LC-MALDI-MS/MS bottom-up proteomics.
AB  - The use of offline liquid chromatography-matrix assisted laser
      desorption/ionization (LC-MALDI) tandem mass spectrometry (MS/MS) for bottom-up
      proteomics offers advantages in terms of cost, ease of use, and the time
      decoupled nature of the separation step and the mass analysis. A method was
      developed to improve the capabilities of LC-MALDI-MS/MS in terms of protein
      identification in a bottom-up proteomic workflow. Enhanced protein identification
      is achieved by an increase in the MALDI signal intensity of the precursor
      peptides brought about by coating the MALDI plate with a thin film of graphite
      powder. Using the Escherichia coli proteome, it is demonstrated that the graphite
      modified MALDI plates used in an offline LC-MALDI-MS/MS bottom-up protocol led to
      a 50-135% increase in the number of peptide identifications, and a concomitant
      21%-105% increase in the number of proteins inferred. We identify factors that
      lead to improvements in peptide sequence identifications and in the number of
      unique proteins identified when compared to using an unmodified MALDI plate.
      These improvements are achieved using a low cost approach that it is easy to
      implement, requires no hardware/protocol modification, it is compatible with LC
      and adds no additional analysis time.

PMID- 29326071
TI  - A rapid fluorescent method for the real-time measurement of poly(ADP-ribose)
      polymerase 1 activity.
AB  - Poly(ADP-ribose) polymerase 1 (PARP1) is a key enzyme that regulates important
      cellular processes, including DNA repair. PARP1 binds to a DNA damage site and
      synthesizes poly(ADP-ribose) chains (PARs), which serve as a signal of DNA damage
      for other DNA repair enzymes. PARP1 is a recognized target for the development of
      anti-cancer drugs. In this work, a method is developed that makes it possible to
      investigate the complex formation of PARP1 with DNA as well as its dissociation
      by detecting the fluorescence anisotropy of this complex during the poly(ADP
      ribose) synthesis. The method allows investigation of the inhibition of PARP1
      activity in the presence of its inhibitors. In this work, we demonstrated that
      PARP1 is activated by DNA duplexes containing a damage and a fluorophore at the
      3'-end of one of the DNA duplex chains. The effects of the clinical inhibitor
      olaparib on the activity of PARP1 was studied. It was shown that olaparib has no
      influence on the binding of PARP1 to the model DNA structures used, but it
      significantly inhibits the poly(ADP-ribosyl)ation of PARP1. The proposed
      convenient method for the real-time determination of the PARP1 activity can be
      used to screen PARP1 inhibitors with the calculation of quantitative inhibition
      parameters.

PMID- 29326072
TI  - Novel 1,4-naphthoquinone derivatives induce apoptosis via ROS-mediated p38/MAPK,
      Akt and STAT3 signaling in human hepatoma Hep3B cells.
AB  - 1,4-Naphthoquinone and its derivatives have shown some efficacy as therapeutic
      compounds for cancer and inflammation, though their clinical application is
      limited by their side-effects. To reduce the toxicity of these compounds and
      optimize their effects, we synthesized two 1,4-naphthoquinone derivatives-2
      butylsulfinyl- 1,4-naphthoquinone (BSNQ) and 2-octylsulfinyl-1,4-naphthoquinone
      (OSNQ)-and investigated their effects and underlying mechanisms in hepatocellular
      carcinoma cells. BSNQ and OSNQ decreased cell viability and significantly induced
      apoptosis, accompanied by the accumulation of reactive oxygen species (ROS).
      However, pretreatment with N-acetyl-l-cysteine, a specific ROS scavenger, blocked
      apoptosis. Western blot results indicated that BSNQ and OSNQ up-regulated the
      phosphorylation of p38 and JNK, and down-regulated the phosphorylation of ERK,
      Akt and STAT3, and that these effects were blocked by N-acetyl-l-cysteine.
      Furthermore, BSNQ and OSNQ suppressed tumor growth and modulated MAPK and STAT3
      signaling in mouse xenografts without detectable effects on body weight or
      hematological parameters. These results indicate that BSNQ and OSNQ induce
      apoptosis in human hepatoma Hep3B cells via ROS-mediated p38/MAPK, Akt and STAT3
      signaling pathways, suggesting that these 1,4-naphthoquinone derivatives may
      provide promising new anticancer agents to treat HCC.

PMID- 29326074
TI  - Overcoming the resistance mechanisms of Smoothened inhibitors.
AB  - Smoothened (Smo), the main transducer of the Hedgehog (Hh) signaling pathway, is
      a promising target for anticancer therapy. Although vismodegib and sonidegib have
      demonstrated effectiveness for the treatment of basal cell carcinoma (BCC), their
      clinical use has been associated with mutation-related drug resistance. In this
      review, we outline the resistance mechanisms of Smo inhibitors and point the way
      for future endeavors. We focus in particular on the development of second
      generation Smo inhibitors based on co-crystal structures, inhibition of
      downstream components, and the regulation of other interacting pathways or
      mediators that could compensate for the inhibitory activity of upstream
      inhibitors.

PMID- 29326073
TI  - Retinoic acid promotes stem cell differentiation and embryonic development by
      transcriptionally activating CFTR.
AB  - Retinoic acid (RA) plays a pivotal role in many cellular processes; however, the
      signaling mechanisms mediating the effect of RA are not fully understood. Here,
      we show that RA transcriptionally upregulates cystic fibrosis transmembrane
      conductance regulator (Cftr) by promoting the direct binding of its receptor
      RARalpha to Cftr promoter in mouse spermatogonia and embryonic stem (ES) cells.
      The RA/CFTR pathway is involved in the differentiation of spermatogonia and
      organogenesis during the embryo development of Xenopus laevis. Loss of CFTR by
      siRNA-mediated knockdown blunts the RA-induced spermatogonial differentiation.
      Overexpression of CFTR mimics the effect of RA on the induction of spermatogonial
      differentiation or restores the developmental defects induced by the knockdown of
      RARalpha in spermatogonial cells and Xenopus laevis. Analysis of the human
      database shows that the expression of CFTR positively correlates with RARalpha in
      brain tissues, stem cells as well as cancers, supporting the role of RA/CFTR
      pathway in various developmental processes in humans. Together, our study
      discovers an essential role of CFTR in mediating the RA-dependent signaling for
      stem cell differentiation and embryonic development.

PMID- 29326075
TI  - Use of CRISPR/Cas9 gene-editing tools for developing models in drug discovery.
AB  - Clustered regularly interspaced short palindromic repeat/CRISPR-associated 9
      (CRISPR/Cas9) enables targeted genome engineering. The simplicity of this system,
      its facile engineering, and amenability to multiplex genes make it the system of
      choice for many applications. This system has revolutionized our ability to carry
      out gene editing, transcription regulation, genome imaging, and epigenetic
      modification. In this review, we discuss the discovery of CRISPR/Cas9, its
      mechanism of action, its application in medicine and animal model development,
      and its delivery. We also highlight how the CRISPR/Cas9 system can affect the
      next generation of drugs by accelerating the identification and validation of
      high-value targets. The generation of precision disease models through this
      system will provide a rapid avenue for functional drug screening.

PMID- 29326076
TI  - Phage-derived lysins as potential agents for eradicating biofilms and persisters.
AB  - Bacterial biofilms are highly resistant to the action of antibiotics. Presence of
      persisters, phenotypically resistant populations of bacterial cells, is thought
      to contribute toward recalcitrance of biofilms. The phage-derived lysins, by
      virtue of their ability to cleave the peptidoglycan of bacterial cells in an
      enzymatic manner, have the unique ability to kill dormant cells. Several lysins
      have shown potent antibiofilm activity in vitro. The fact that lysins have shown
      better efficacy than conventional drugs in animal models of endocarditis and
      other infections involving biofilms suggests that the lysins can potentially be
      developed against difficult-to-treat bacterial infections.

PMID- 29326077
TI  - Mechanism of nanoparticle-induced hypersensitivity in pigs: complement or not
      complement?
AB  - A recent study on nanoparticle-induced hypersensitivity reactions in pigs showed
      robust pulmonary intravascular macrophage clearance of Polybead(r) carboxylate
      microspheres in mediating the adverse cardiopulmonary distress, irrespective of
      the ability of these particles to activate the complement (C) system in vitro.
      Focusing on this observation, this article highlights the controversies in
      projecting in vitro C assay data to in vivo conditions and applying data on
      polystyrene particles to therapeutic nanopharmaceuticals. Based on overwhelming
      evidence of a role of anaphylatoxins in hypersensitivity reactions, the need to
      further explore the role of C activation in the reported and other reactions is
      highlighted. C-activation-related and C-independent pseudoallergies (CARPA and
      CIPA) can proceed simultaneously, as outlined by the 'double-hit' hypothesis.

PMID- 29326078
TI  - NCp7: targeting a multitask protein for next-generation anti-HIV drug development
      part 2. Noncovalent inhibitors and nucleic acid binders.
AB  - Nucleocapsid protein 7 (NCp7) represents a viable target not yet reached by the
      currently available antiretrovirals. It is a small and highly basic protein,
      which is essential for multiple stages of the viral replicative cycle, with its
      structure preserved in all viral strains, including clinical isolates. NCp7 can
      be inhibited covalently, noncovalently and by shielding the nucleic acid (NA)
      substrates of its chaperone activity. Although covalent NCp7 inhibitors have
      already been detailed in the first part of this review series, the focus here is
      based on noncovalent and NA-binder inhibitors and on the analysis of the NCp7 3D
      structure to deliver fruitful insights for future drug design strategies.

PMID- 29326079
TI  - Unlocking the full potential of open innovation in the life sciences through a
      classification system.
AB  - A common understanding of expectations and requirements is critical for boosting
      research-driven business opportunities in open innovation (OI) settings.
      Transparent communication requires common definitions and standards for OI to
      align the expectations of both parties. Here, we suggest a five-level
      classification system for OI models, reflecting the degree of openness. The aim
      of this classification system is to reduce contract negotiation complexity and
      times between two parties looking to engage in OI. Systematizing definitions and
      contractual terms for OI in the life sciences helps to reduce entry barriers and
      boosts collaborative value generation. By providing a contractual framework with
      predefined rules, science will be allowed to move more freely, thus maximizing
      the potential of OI.

PMID- 29326080
TI  - Light-triggerable formulations for the intracellular controlled release of
      biomolecules.
AB  - New therapies based on the use of biomolecules [e.g., proteins, peptides, and non
      coding (nc)RNAs] have emerged during the past few years. Given their instability,
      adverse effects, and limited ability to cross cell membranes, delivery systems
      are required to fully reveal their biological potential. Sophisticated
      nanoformulations responsive to light offer an excellent opportunity for the
      controlled release of these biomolecules, enabling the control of timing,
      duration, location, and dosage. In this review, we discuss the design principles
      for the delivery of biomolecules, in particular proteins and RNA-based
      therapeutics, by light-triggerable formulations. We further discuss the
      opportunities offered by these formulations in terms of endosomal escape, as well
      as their limitations.

PMID- 29326081
TI  - Macromolecule nanotherapeutics: approaches and challenges.
AB  - With the advent of technology, newer forms of drugs, such as proteins, DNA, and
      RNA, have entered mainstream product development. However, systemic delivery of
      macromolecules is limited by rapid blood clearance, poor stability in vivo, and
      inadequate uptake by cells. Nanoparticle (NP)-based delivery systems have emerged
      as suitable carriers for overcoming such pharmacokinetic limitations of
      macromolecule delivery. Nanocarriers, such as liposomes, provide protection for
      sensitive drug materials and also enhance the circulation half-life of
      therapeutics. Nanocarriers have also been shown to promote cellular uptake and
      the release of intact macromolecules in the cell. Besides liposomes, other
      nanocarriers, such as gold and iron oxide NPs, are also now being tested in
      clinical trials.

PMID- 29326082
TI  - Pharmaceutical nanocrystals: production by wet milling and applications.
AB  - Nanocrystals are regarded as an important nanoformulation approach exhibiting
      advantages of increased dissolution and saturation solubility with chemical
      stability and low toxicity. Nanocrystals are produced in the form of
      nanosuspensions using top-down (e.g., wet milling or high pressure
      homogenization) and bottom-up methods (e.g., antisolvent precipitation). Wet
      milling is a scalable method applicable to drugs with different physicochemical
      and mechanical properties. Nanocrystalline-based formulations, either as liquid
      nanosuspensions or after downstream processing to solid dosage forms, have been
      developed as drug delivery systems for various routes of administration (i.e.,
      oral, parenteral, pulmonary, ocular, and dermal). In this review, we summarize
      and discuss the features, preparation methods, and therapeutic applications of
      pharmaceutical nanocrystals, highlighting their universality as a formulation
      approach for poorly soluble drugs.

PMID- 29326084
TI  - Impact of intracellular ionic strength on dimer binding in the NF-kB Inducing
      kinase.
AB  - Improper signaling of the nuclear factor-kappaB (NF-kappaB) pathway plays a
      critical role in many inflammatory disease states including cancer, stroke, and
      viral infections. Although the signaling pathways are known, how these molecular
      mechanisms respond to changes in the intracellular microenvironment such as pH,
      ionic strength, and temperature, remains elusive. Molecular dynamics simulations
      were employed to differentiate the structural dynamics of the NF-kappaB Inducing
      Kinase (NIK), a protein kinase responsible for invoking the non-canonical NF
      kappaB pathway, in its native and mutant form, and in the absence and presence of
      salt concentration in efforts to probe whether changes in the ionic environment
      stabilize or destabilize the NIK dimer. Analyses of structure-activity and
      conformational-activity relationships indicate that the protein-protein
      interactions are sensitive to changes in the ionic strength. Ligand binding
      pockets as well as regions between the oligomer interface either compress or
      expand, affecting both local and distal intermolecular interactions that result
      in stabilization or destabilization in the protein assembly.

PMID- 29326083
TI  - Ligandomics: a paradigm shift in biological drug discovery.
AB  - As productivity of pharmaceutical research and development (R&D) for small
      molecule drugs declines, the trend in drug discovery strategies is shifting
      towards biologics, which predominantly target secreted or cell surface proteins.
      Receptors and ligands are the most-valuable drug targets. In contrast to
      conventional approaches of discovering one ligand at a time, the emerging
      technology of ligandomics can systematically map disease-selective cellular
      ligands in the absence of molecular probes. Biologics targeting these ligands
      with disease selectivity have the advantages of high efficacy, minimal adverse
      effects, wide therapeutic indices, and low safety-related attrition rates.
      Therefore, ligandomics represents a paradigm shift to address the bottleneck of
      target discovery for biologics development.

PMID- 29326085
TI  - Frailty and leucocyte count are predictors of all-cause mortality and
      hospitalization length in non-demented institutionalized older women.
AB  - Alteration in the immune system such as the number of white blood cells count
      (WBC) has been associated with frailty syndrome but their role in
      institutionalized older individuals have been rarely investigated. We evaluated
      the relationships between white blood cell subtypes, geriatric assessment,
      depression and frailty syndrome based on the criteria of physical phenotype. In
      particular, we aimed to analyze by a two-year follow-up and prospective study the
      predictive value of alterations in WBC, frailty and functional impairment in
      terms of hospitalizations and all-cause mortality in institutionalized older
      women. There was a significant and inverse correlation between the frailty score
      and lymphocyte count at baseline but it did not display any predictive effect for
      the outcomes (hospitalizations and mortality). In contrast, monocytes count was
      significantly correlated with number of hospital stays and predicted
      hospitalizations in the follow-up. High frailty score directly and better
      functional status (Barthel score) inversely predicted mortality in the follow-up
      with an HR of 1.87 (95%CI: 1.04-3.35), and 0.97 (95% CI: 0.96-0.99) (p < .05 in
      both cases). Further investigation into the role of white blood cell subtypes in
      aging and its associated adverse outcomes in older adults is warranted. Physical
      phenotype of frailty besides general population, also predicted mortality in
      older institutionalized women and deserves specific intervention in this subgroup
      of older individuals.

PMID- 29326086
TI  - Reply: Pentraxin-3 and coronary artery disease.

PMID- 29326087
TI  - A multicomponent exercise program improves physical function in long-term nursing
      home residents: A randomized controlled trial.
AB  - To investigate the impact of a multicomponent exercise program on anthropometry,
      physical function, and physical activity on older adults living in long-term
      nursing homes (LTNH), we conducted a randomized controlled trial involving 112
      participants aged 84.9 +/- 6.9 years. Participants were randomly assigned to an
      intervention (IG) or control group (CG). The IG participated in a 3-month
      multicomponent exercise intervention focused on strength, balance, stretching
      exercises, and walking recommendations. Subjects in the CG participated in
      routine activities. Analyses of outcome parameters were performed in the entire
      sample and in two subgroups, classified according to participants' physical
      function score at baseline. The group-by-time interaction, favoring the IG, was
      significant for the entire sample and for the participants in the low physical
      function subgroup for the following parameters: waist circumference, 30-s chair
      stand, arm-curl, 8-ft timed up-and-go, SPPB score, gait speed, and Berg scale (p
      < .05). In participants with higher physical function at baseline, significant
      group-by-time interaction was observed in the SPPB score and Berg scale (p <
      .05). When differences were analyzed within groups, the IG maintained or improved
      in all assessed parameters, while participants in the CG showed a marked decline.
      Our study showed that a multicomponent exercise program is effective for older
      people living in LTNH. This is especially relevant in those with lower physical
      function scores. The lower efficacy of the program in participants with better
      function might be due to the insufficient exercise demands of our intervention
      for more fit residents. Future studies should analyze the effects of programs
      with higher intensities in older people with intermediate to high physical
      function.

PMID- 29326088
TI  - Age effects of distinct immune checkpoint blockade treatments in a mouse melanoma
      model.
AB  - Cancer immunotherapy has shown remarkable recent progress. Immune checkpoint
      blocking antibodies have become the most successful anti-cancer agent class ever
      developed, with six distinct agents approved since 2011 for a wide variety of
      cancers. Although age is the biggest risk factor for cancer (aside from selected
      early-onset pediatric cancers), these agents were tested pre-clinically in young
      hosts, and there is remarkably little published on the effects of host age on
      treatment outcomes in pre-clinical studies or human clinical trials. The three
      principal immune checkpoints against which blocking antibodies have been FDA
      approved for human use are CTLA-4, PD-1 and PD-L1. We used a mouse model of
      transplantable, orthotopic B16 melanoma to test age effects of treatments with
      anti-CTLA-4, anti-PD-1 and anti-PD-L1 antibodies. All three agents were highly
      effective in treating young tumor-bearing hosts as expected. Anti-PD-L1 as a
      single agent had no effect on tumor growth in aged hosts, anti-CTLA-4 had
      detectable, modest effects and anti-PD-1 was essentially as effective in aged as
      in young hosts, the first single agent we have identified not to lose efficacy
      with age in this model. Other important differences in young versus aged hosts
      included lack of anti-CTLA-4-mediated depletion of intratumor regulatory T cells
      in aged hosts and poorer ability of all three agents to activate T cells in aged
      versus young hosts. Anti-CTLA-4 efficacy appeared to improve when combined with
      anti-PD-L1. Regulatory T cell depletion with FDA-approved denileukin diftitox did
      not improve treatment by any single agent. Aged mice tolerated treatments as well
      as young mice without obvious toxicities at equivalent doses.

PMID- 29326089
TI  - Markers of oxidative stress, skeletal muscle mass and function, and their
      responses to resistance exercise training in older adults.
AB  - BACKGROUND: Oxidative stress (OS) negatively affects skeletal muscle homeostasis
      in experimental models of ageing. However, little is known about the associations
      between circulating OS markers and parameters of muscle mass and function, and
      their responses to exercise training, in humans. METHODS: Maximal voluntary
      contraction (MVC, primary outcome) and isokinetic torque of the knee extensors at
      30 degrees  s-1 (MIT), muscle cross-sectional area (MCSA) and quality (MQ,
      secondary outcomes), and plasma concentrations of malondialdehyde (MDA, pro-OS),
      homocysteine (HCY, pro-OS), taurine (TAU, anti-OS), and protein sulphydryl groups
      (PSH, anti-OS) were measured in 27 healthy older males and 23 females at baseline
      and after an 18-week resistance exercise program, with or without a nutritional
      intervention (fish oil vs. placebo). RESULTS: After adjusting for age, glomerular
      filtration rate, and nutritional intervention, there were no significant
      correlations between baseline OS markers and muscle parameters, barring a
      positive association between TAU and MIT in females (r = 0.53, P = .035) and
      between MDA and MCSA in males (r = 0.69, P = .001). Training did not
      significantly change OS markers, except for a reduction in MDA in females (-0.27
      MUmol/L, 95% CI -0.51 to -0.02, P = .034). In females, there were significant
      correlations between baseline MDA and exercise-induced changes in MVC (P = .018),
      baseline TAU and changes in MCSA (P = .026), and baseline HCY and changes in MCSA
      (P = .046) and MQ (P = .022). In males, baseline MDA was significantly associated
      with exercise-induced changes in MVC (P = .040). CONCLUSIONS: Plasma MDA, HCY,
      and TAU were significantly associated with baseline and/or exercise-induced
      changes in muscle mass and function in healthy older adults, primarily in
      females. Pending further confirmation in other populations, specific OS markers,
      particularly MDA, might predict muscle responses to resistance exercise programs
      in old age.

PMID- 29326091
TI  - Erratum: "Regulation of Chromatin Assembly and Cell Transformation by
      Formaldehyde Exposure in Human Cells".
AB  - [This corrects the article DOI: 10.1289/EHP1275.].

PMID- 29326090
TI  - The Addition of Chemotherapy to Radiation Therapy Improves Survival in Elderly
      Patients with Stage III Non-Small Cell Lung Cancer.
AB  - INTRODUCTION: Elderly patients account for the majority of lung cancer diagnoses
      but are poorly represented in clinical trials. We evaluated the overall survival
      (OS) of elderly patients with stage III NSCLC treated with definitive radiation
      compared with that of patients treated with definitive chemoradiation. METHODS:
      We conducted a comparative effectiveness study of radiation therapy versus
      chemoradiation in elderly (>=70 years old) patients with stage III NSCLC not
      treated surgically diagnosed from 2003 to 2014; the patients were identified by
      using the National Cancer Database. Two cohorts were evaluated: patients (n =
      5023) treated with definitive radiation (>=59.4 Gy) and patients (n = 18,206)
      treated with definitive chemoradiation. Chemoradiation was further defined as
      concurrent (radiation and chemotherapy started within 30 days of each other) or
      sequential (radiation started >30 days after chemotherapy). We compared OS
      between the treatment groups by using the Kaplan-Meier method and Cox
      proportional hazards regression before and after propensity score matching (PSM).
      RESULTS: Treatment with chemoradiation was associated with improved OS versus
      that with radiation both before PSM (hazard ratio [HR] = 0.66, 95% confidence
      interval [CI]: 0.64-0.68, p < 0.001) and after PSM (HR = 0.67, 95% CI: 0.64-0.70,
      p < 0.001). Relative to concurrent chemoradiation, sequential chemoradiation was
      associated with a 9% reduction in the risk for death (HR = 0.91, 95% CI: 0.85
      0.96, p = 0.002). CONCLUSIONS: We found that definitive chemoradiation resulted
      in a survival advantage compared with definitive radiation in elderly patients.
      Sequential chemotherapy and radiation was superior to concurrent chemoradiation.
      Although prospective trials are needed, this analysis suggests that
      chemoradiation should be strongly considered for elderly patients and the optimal
      sequencing of chemotherapy and radiation remains an unanswered question for this
      patient population.

PMID- 29326092
TI  - Usage of an Exercise App in the Care for People With Osteoarthritis: User-Driven
      Exploratory Study.
AB  - BACKGROUND: Exercise has proven to reduce pain and increase quality of life among
      people living with osteoarthritis (OA). However, one major challenge is adherence
      to exercise once supervision ends. OBJECTIVE: This study aimed to identify mental
      and physical barriers and motivational and social aspects of training at home,
      and to test or further develop an exercise app. METHODS: The study was inspired
      from participatory design, engaging users in the research process. Data were
      collected through focus groups and workshops, and analyzed by systematic text
      condensation. RESULTS: Three main themes were found: competition as motivation,
      training together, and barriers. The results revealed that the participants
      wanted to do their training and had knowledge on exercise and pain but found it
      hard to motivate themselves. They missed the observation, comments, and
      encouragement by the supervising physiotherapist as well as their peers. Ways to
      optimize the training app were identified during the workshops as participants
      shared their experience. CONCLUSIONS: This study concludes that the long-term
      continuation of exercising for patients with OA could be improved with the use of
      a technology tailored to users' needs, including motivational and other
      behavioral factors.

PMID- 29326093
TI  - Face-to-Face Versus Mobile Versus Blended Weight Loss Program: Randomized
      Clinical Trial.
AB  - BACKGROUND: Conventional face-to-face weight loss and weight control programs are
      very labor intensive for both the patient and the provider. It is unclear to what
      extent conventional programs can be (partially) completed by mobile health
      (mHealth) apps. OBJECTIVE: The aim of this study was to compare the effectiveness
      of different weight loss programs using a combination of conventional and mobile
      programs among adults who are overweight (body mass index [BMI]>29 kg/m2).
      METHODS: A single-blinded randomized controlled trial among obese adults was
      performed from September 2015 to March 2016. The study took place in Leuven,
      Belgium. Of the 102 eligible (BMI >29 kg/m2) adults, 81 (79%) completed the
      study. The three intervention groups consisted of a conventional face-to-face
      weight loss program, a weight loss app program (app group), and a partial face-to
      face and partial app program (combi group). All intervention groups received the
      same advice from a dietician and a physical activity coach during a 12-week
      period. The control group did not receive any information during the same period.
      Primary outcomes were weight reduction (5% decrease of baseline weight in kg),
      BMI, metabolic risk factors, dietary pattern, and physical activity. RESULTS:
      Significant more participants in all three intervention groups lost at least 5%
      or more of their weight at baseline compared with the control group. No
      significant difference was found between the combi group and the conventional
      group. A trend was found that more participants in the combi group lost 5% or
      more compared with the app group (19%), P=.06. A significant time x group effect
      was found for BMI and metabolic risk factors, with the control group having the
      worst results and the combi group being significantly better with regard to BMI
      compared with the app group. No significant group x time effects were found for
      the intake of different food and drinks and moderate to vigorous physical
      activity (MVPA). CONCLUSIONS: The results of this study show that a conventional
      weight loss program could partially be completed with an mHealth program without
      affecting the effectiveness. TRIAL REGISTRATION: Clinicaltrials.gov NCT02595671;
      https://clinicaltrials.gov/ct2/show/NCT02595671 (Archived by WebCite at
      http://www.webcitation.org/6w1H0x1Q6).

PMID- 29326094
TI  - A Shared Decision-Making Tool to Prevent Substance Abuse: Protocol for a
      Randomized Controlled Trial.
AB  - BACKGROUND: Substance use disorder (SUD) affects over 20 million adults and costs
      over $700 billion annually in the United States. It is one the greatest health
      care challenges we face. OBJECTIVE: This research project seeks to enhance the
      standard practice of Screening, Brief Intervention, and Referral to Treatment
      (SBIRT) through a mobile solution easily incorporated into primary care that will
      promote shared decision making and increase referral and adherence to specialty
      care through continued follow-up care. METHODS: This research will conduct an
      Office of Management and Budget (OMB)-approved randomized controlled trial (RCT)
      in primary care and SUD specialty service providers. The RCT will recruit a total
      of 500 SUD patients. Recruited patients will be randomized into control and
      intervention arms. Both arms will take initial baseline and exit (30 days)
      surveys to evaluate self-reported substance use and specialty service
      utilization. The control arm patients will receive usual care. The intervention
      group patients will receive technology-enhanced SBIRT and a mobile follow-up
      program to track goals and substance use at home. The RCT tracks participants for
      30 days after the primary care encounter. We will collect feedback from the
      patients during the 30 days and count the number of patients who use specialty
      care services in specialty care programs for tobacco, alcohol, and drug abuse
      (both from self-reporting and from the service providers). RESULTS: RCT and data
      collection are underway. We expect to report the data results in 2018.
      CONCLUSIONS: We expect that significantly more intervention group patients will
      receive specialty SUD care within 30 days following the SBIRT encounter at the
      primary care clinic compared to the control group. We also expect that the
      intervention group patients will report a greater reduction in substance use and
      a greater drop in Drug Abuse Screening Test and Addition Severity Index scores
      within 30 days.

PMID- 29326095
TI  - Development of a Maternal, Newborn and Child mHealth Intervention in Thai Nguyen
      Province, Vietnam: Protocol for the mMom Project.
AB  - BACKGROUND: Ethnic minority women (EMW) living in mountainous areas of northern
      Vietnam have disproportionately high infant and maternal mortality rates as a
      result of low maternal health knowledge, poverty, and remoteness from low
      capacity health centers. OBJECTIVE: The objective of this study was to describe
      the protocol for the development and evaluation of the mMom intervention, which
      is an integrated mobile health (mHealth) system designed to improve maternal and
      infant health knowledge, and behavior among women in remote areas of Thai Nguyen,
      Vietnam. METHODS: This project featured the following four phases: (1)
      development of an mHealth platform integrated into the existing health management
      information system in partnership with the provincial health department; (2)
      ethnographic fieldwork and intervention content development; (3) intervention
      piloting and implementation; and (4) evaluation of the intervention's impact on
      participants' maternal health knowledge, behavior, and interactions with the
      health system. RESULTS: The mMom project development process resulted in the
      following: (1) the successful development of the mMom system, including the
      mHealth platform hardware and integration, the intervention plan and content, and
      the monitoring and evaluation framework; (2) the piloting and implementation of
      the intervention as planned; and (3) the implementation of the monitoring and
      evaluation framework components. CONCLUSIONS: This protocol outlines the
      development of the mMom intervention and describes critical next steps in
      understanding the impact of the intervention on participants and the wider health
      system in Thai Nguyen province, Vietnam.

PMID- 29326096
TI  - Monitoring Freshman College Experience Through Content Analysis of Tweets:
      Observational Study.
AB  - BACKGROUND: Freshman experiences can greatly influence students' success.
      Traditional methods of monitoring the freshman experience, such as conducting
      surveys, can be resource intensive and time consuming. Social media, such as
      Twitter, enable users to share their daily experiences. Thus, it may be possible
      to use Twitter to monitor students' postsecondary experience. OBJECTIVE: Our
      objectives were to (1) describe the proportion of content posted on Twitter by
      college students relating to academic studies, personal health, and social life
      throughout the semester; and (2) examine whether the proportion of content
      differed by demographics and during nonexam versus exam periods. METHODS: Between
      October 5 and December 11, 2015, we collected tweets from 170 freshmen attending
      the University of California Los Angeles, California, USA, aged 18 to 20 years.
      We categorized the tweets into topics related to academic, personal health, and
      social life using keyword searches. Mann-Whitney U and Kruskal-Wallis H tests
      examined whether the content posted differed by sex, ethnicity, and major. The
      Friedman test determined whether the total number of tweets and percentage of
      tweets related to academic studies, personal health, and social life differed
      between nonexam (weeks 1-8) and final exam (weeks 9 and 10) periods. RESULTS:
      Participants posted 24,421 tweets during the fall semester. Academic-related
      tweets (n=3433, 14.06%) were the most prevalent during the entire semester,
      compared with tweets related to personal health (n=2483, 10.17%) and social life
      (n=1646, 6.74%). The proportion of academic-related tweets increased during final
      exam compared with nonexam periods (mean rank 68.9, mean 18%, standard error (SE)
      0.1% vs mean rank 80.7, mean 21%, SE 0.2%; Z=-2.1, P=.04). Meanwhile, the
      proportion of tweets related to social life decreased during final exams compared
      with nonexam periods (mean rank 70.2, mean 5.4%, SE 0.01% vs mean rank 81.8, mean
      7.4%, SE 0.01%; Z=-4.8, P<.001). Women tweeted more often than men during both
      nonexam (mean rank 95.8 vs 76.8; U=2876, P=.02) and final-exam periods (mean rank
      96.2 vs 76.2; U=2832, P=.01). The percentages of academic-related tweets were
      similar between ethnic groups during nonexam periods (P>.05). However, during the
      final-exam periods, the percentage of academic tweets was significantly lower
      among African Americans than whites (chi24=15.1, P=.004). The percentages of
      tweets related to academic studies, personal health, and social life were not
      significantly different between areas of study during nonexam and exam periods
      (P>.05). CONCLUSIONS: The results suggest that the number of tweets related to
      academic studies and social life fluctuates to reflect real-time events.
      Student's ethnicity influenced the proportion of academic-related tweets posted.
      The findings from this study provide valuable information on the types of
      information that could be extracted from social media data. This information can
      be valuable for school administrators and researchers to improve students'
      university experience.

PMID- 29326097
TI  - Turning Good Intentions Into Actions by Using the Health Action Process Approach
      to Predict Adherence to Internet-Based Depression Prevention: Secondary Analysis
      of a Randomized Controlled Trial.
AB  - BACKGROUND: Many individuals engaging in Internet-based interventions fail to
      complete these treatments as intended. The processes responsible for treatment
      adherence in Internet-based interventions are still poorly understood. OBJECTIVE:
      The aim of this study was to investigate to what extent adherence in an Internet
      based intervention can be predicted by motivational and volitional factors
      outlined in the health action process approach (HAPA). METHODS: This study
      investigated motivational and volitional factors included in HAPA in a randomized
      controlled trial to predict treatment adherence of N=101 individuals with
      subclinical depression in the intervention group of a depression prevention
      intervention (GET.ON Mood Enhancer). Adherence was operationalized as the number
      of completed treatment modules. Using longitudinal structural equation modeling,
      HAPA variables (motivational, maintenance, and recovery self-efficacy, outcome
      expectancies, intention, and planning) were assessed at baseline and their
      associations with adherence 7 weeks later. RESULTS: Planning predicted adherence.
      Better planning was, in turn, associated with higher levels of maintenance self
      efficacy, and the latter significantly affected treatment adherence via planning.
      The other hypothesized direct associations were not significant. In total, the
      HAPA variables accounted for 14% of variance in treatment adherence. CONCLUSIONS:
      Planning emerged as the strongest predictor of treatment adherence in highly
      motivated participants in an Internet-based intervention out of all HAPA
      variables investigated. Findings are in line with the hypothesis that planning
      facilitates the translation of good intentions into actions. The findings imply
      that systematically fostering planning skills and maintenance self-efficacy prior
      to or during Internet-based interventions would help participants to successfully
      complete these treatments. TRIAL REGISTRATION: German Clinical Trials Register
      DRKS00005973; https://www.drks.de/drks_web/navigate.do?
      navigationId=trial.HTML&TRIAL_ID=DRKS00005973 (Archived by WebCite at
      http://www.webcitation.org/6uxCy64sy).

PMID- 29326098
TI  - Cognitive and Behavioral Skills Exercises Completed by Patients with Major
      Depression During Smartphone Cognitive Behavioral Therapy: Secondary Analysis of
      a Randomized Controlled Trial.
AB  - BACKGROUND: A strong and growing body of evidence has demonstrated the
      effectiveness of cognitive behavioral therapy (CBT), either face-to-face, in
      person, or as self-help via the Internet, for depression. However, CBT is a
      complex intervention consisting of several putatively effective components, and
      how each component may or may not contribute to the overall effectiveness of CBT
      is poorly understood. OBJECTIVE: The aim of this study was to investigate how the
      users of smartphone CBT use and benefit from various components of the program.
      METHODS: This is a secondary analysis from a 9-week, single-blind, randomized
      controlled trial that has demonstrated the effectiveness of adjunctive use of
      smartphone CBT (Kokoro-App) over antidepressant pharmacotherapy alone among
      patients with drug-resistant major depressive disorder (total n=164, standardized
      mean difference in depression severity at week 9=0.40, J Med Internet Res).
      Kokoro-App consists of three cognitive behavioral skills of self-monitoring,
      behavioral activation, and cognitive restructuring, with corresponding worksheets
      to fill in. All activities of the participants learning each session of the
      program and completing each worksheet were uploaded onto Kokoro-Web, which each
      patient could use for self-check. We examined what use characteristics
      differentiated the more successful users of the CBT app from the less successful
      ones, split at the median of change in depression severity. RESULTS: A total of
      81 patients with major depression were allocated to the smartphone CBT. On
      average, they completed 7.0 (standard deviation [SD] 1.4) out of 8 sessions of
      the program; it took them 10.8 (SD 4.2) days to complete one session, during
      which they spent 62 min (SD 96) on the app. There were no statistically
      significant differences in the number of sessions completed, time spent for the
      program, or the number of completed self-monitoring worksheets between the
      beneficiaries and the nonbeneficiaries. However, the former completed more
      behavioral activation tasks, engaged in different types of activities, and also
      filled in more cognitive restructuring worksheets than the latter. Activities
      such as "test-drive a new car," "go to a coffee shop after lunch," or "call up an
      old friend" were found to be particularly rewarding. All cognitive restructuring
      strategies were found to significantly decrease the distress level, with "What
      would be your advice to a friend who has a similar problem?" found more helpful
      than some other strategies. CONCLUSIONS: The CBT program offered via smartphone
      and connected to the remote server is not only effective in alleviating
      depression but also opens a new avenue in gathering information of what and how
      each participant may utilize the program. The activities and strategies found
      useful in this analysis will provide valuable information in brush-ups of the
      program itself and of mobile health (mHealth) in general. TRIAL REGISTRATION:
      Japanese Clinical Trials Registry UMIN CTR 000013693;
      https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ ctr_view.cgi?recptno=R000015984
      (Archived by WebCite at http://www.webcitation.org/6u6pxVwik).

PMID- 29326100
TI  - Spend more on NHS or see services deteriorate further, hospital leaders warn.

PMID- 29326101
TI  - Pathways over Time: Functional Genomics Research in an Introductory Laboratory
      Course.
AB  - National reports have called for the introduction of research experiences
      throughout the undergraduate curriculum, but practical implementation at many
      institutions faces challenges associated with sustainability, cost, and large
      student populations. We describe a novel course-based undergraduate research
      experience (CURE) that introduces introductory-level students to research in
      functional genomics in a 3-credit, multisection laboratory class. In the Pathways
      over Time class project, students study the functional conservation of the
      methionine biosynthetic pathway between divergent yeast species. Over the five
      semesters described in this study, students (N = 793) showed statistically
      significant and sizable growth in content knowledge (d = 1.85) and in self
      reported research methods skills (d = 0.65), experimental design, oral and
      written communication, database use, and collaboration. Statistical analyses
      indicated that content knowledge growth was larger for underrepresented minority
      students and that growth in content knowledge, but not research skills, varied by
      course section. Our findings add to the growing body of evidence that CUREs can
      support the scientific development of large numbers of students with diverse
      characteristics. The Pathways over Time project is designed to be sustainable and
      readily adapted to other institutional settings.

PMID- 29326099
TI  - Interleukin-18 diagnostically distinguishes and pathogenically promotes human and
      murine macrophage activation syndrome.
AB  - Hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS)
      are life-threatening hyperferritinemic systemic inflammatory disorders. Although
      profound cytotoxic impairment causes familial HLH (fHLH), the mechanisms driving
      non-fHLH and MAS are largely unknown. MAS occurs in patients with suspected
      rheumatic disease, but the mechanistic basis for its distinction is unclear.
      Recently, a syndrome of recurrent MAS with infantile enterocolitis caused by
      NLRC4 inflammasome hyperactivity highlighted the potential importance of
      interleukin-18 (IL-18). We tested this association in hyperferritinemic and
      autoinflammatory patients and found a dramatic correlation of MAS risk with
      chronic (sometimes lifelong) elevation of mature IL-18, particularly with IL-18
      unbound by IL-18 binding protein, or free IL-18. In a mouse engineered to carry a
      disease-causing germ line NLRC4T337S mutation, we observed inflammasome
      dependent, chronic IL-18 elevation. Surprisingly, this NLRC4T337S-induced
      systemic IL-18 elevation derived entirely from intestinal epithelia. NLRC4T337S
      intestines were histologically normal but showed increased epithelial turnover
      and upregulation of interferon-gamma-induced genes. Assessing cellular and tissue
      expression, classical inflammasome components such as Il1b, Nlrp3, and Mefv
      predominated in neutrophils, whereas Nlrc4 and Il18 were distinctly epithelial.
      Demonstrating the importance of free IL-18, Il18 transgenic mice exhibited free
      IL-18 elevation and more severe experimental MAS. NLRC4T337S mice, whose free IL
      18 levels were normal, did not. Thus, we describe a unique connection between MAS
      risk and chronic IL-18, identify epithelial inflammasome hyperactivity as a
      potential source, and demonstrate the pathogenicity of free IL-18. These data
      suggest an IL-18-driven pathway, complementary to the cytotoxic impairment of
      fHLH, with potential as a distinguishing biomarker and therapeutic target in MAS.

PMID- 29326103
TI  - Understanding the Complex Relationship between Critical Thinking and Science
      Reasoning among Undergraduate Thesis Writers.
AB  - Developing critical-thinking and scientific reasoning skills are core learning
      objectives of science education, but little empirical evidence exists regarding
      the interrelationships between these constructs. Writing effectively fosters
      students' development of these constructs, and it offers a unique window into
      studying how they relate. In this study of undergraduate thesis writing in
      biology at two universities, we examine how scientific reasoning exhibited in
      writing (assessed using the Biology Thesis Assessment Protocol) relates to
      general and specific critical-thinking skills (assessed using the California
      Critical Thinking Skills Test), and we consider implications for instruction. We
      find that scientific reasoning in writing is strongly related to inference, while
      other aspects of science reasoning that emerge in writing (epistemological
      considerations, writing conventions, etc.) are not significantly related to
      critical-thinking skills. Science reasoning in writing is not merely a proxy for
      critical thinking. In linking features of students' writing to their critical
      thinking skills, this study 1) provides a bridge to prior work suggesting that
      engagement in science writing enhances critical thinking and 2) serves as a
      foundational step for subsequently determining whether instruction focused
      explicitly on developing critical-thinking skills (particularly inference) can
      actually improve students' scientific reasoning in their writing.

PMID- 29326104
TI  - Rethinking neoadjuvant chemotherapy for breast cancer.

PMID- 29326105
TI  - Chronic limb threatening ischaemia.

PMID- 29326102
TI  - Collectively Improving Our Teaching: Attempting Biology Department-wide
      Professional Development in Scientific Teaching.
AB  - Many efforts to improve science teaching in higher education focus on a few
      faculty members at an institution at a time, with limited published evidence on
      attempts to engage faculty across entire departments. We created a long-term,
      department-wide collaborative professional development program, Biology Faculty
      Explorations in Scientific Teaching (Biology FEST). Across 3 years of Biology
      FEST, 89% of the department's faculty completed a weeklong scientific teaching
      institute, and 83% of eligible instructors participated in additional semester
      long follow-up programs. A semester after institute completion, the majority of
      Biology FEST alumni reported adding active learning to their courses. These
      instructor self-reports were corroborated by audio analysis of classroom noise
      and surveys of students in biology courses on the frequency of active-learning
      techniques used in classes taught by Biology FEST alumni and nonalumni. Three
      years after Biology FEST launched, faculty participants overwhelmingly reported
      that their teaching was positively affected. Unexpectedly, most respondents also
      believed that they had improved relationships with departmental colleagues and
      felt a greater sense of belonging to the department. Overall, our results
      indicate that biology department-wide collaborative efforts to develop scientific
      teaching skills can indeed attract large numbers of faculty, spark widespread
      change in teaching practices, and improve departmental relations.

PMID- 29326109
TI  - Current recommendations for anticoagulant therapy in patients with valvular heart
      disease and atrial fibrillation: the ACC/AHA and ESC/EACTS Guidelines in
      Harmony...but not Lockstep!

PMID- 29326108
TI  - Short-term risk of cardiovascular readmission following a hypertensive disorder
      of pregnancy.
AB  - OBJECTIVE: Women with pregnancies complicated by hypertensive disorders of
      pregnancy (HDP) have increased long-term cardiovascular (CV) risk. We sought to
      determine if they demonstrate increased short-term CV risk. METHODS: Using
      administrative records, all hospital-based deliveries in Florida from 2004 to
      2010 and subsequent readmission to any Florida hospital within 3 years of index
      delivery were identified. Deliveries and clinical diagnoses were determined using
      International Classification of Diseases, Ninth Revision, Clinical Modification
      codes. HDP included pregnancies complicated by gestational hypertension, pre
      eclampsia or eclampsia. Outcomes were CV readmission (acute myocardial
      infarction, stroke or heart failure), non-CV readmission and any readmission
      within 3 years of delivery excluding subsequent deliveries. Associations were
      determined using multivariate logistic regression. RESULTS: Among 1 452 926
      records from delivering mothers of singleton infants (mean age 27.2+/-6.2 years;
      52% white, 23% African American (AA), 18% Hispanic), there were 4054 CV and 259
      252 non-CV readmissions. Women with HDP had higher CV readmission rates (6.4 vs
      2.5/1000 deliveries; P<0.001). AA women had higher rates of CV readmission than
      whites or Hispanics (6.8 vs 1.7 vs 1.0/1000 deliveries, respectively; P<0.001).
      Women with HDP had higher multivariate risk of CV readmission (OR 2.41; 95% CI
      2.08 to 2.80) and any readmission (OR 1.13; 95% CI 1.10 to 1.15). Compared with
      whites, AA women had higher risk for CV readmission (OR 3.60; 95% CI 3.32 to
      3.90) after adjustment for HDP. CONCLUSION: Women with HDP had twice the risk of
      CV readmission within 3 years of delivery, with higher rates among AA women. More
      work is needed to explore preventive strategies for HDP-associated events.

PMID- 29326106
TI  - Risk of Hypoglycemia Following Hospital Discharge in Patients With Diabetes and
      Acute Kidney Injury.
AB  - OBJECTIVE: Hypoglycemia is common in patients with diabetes. The risk of
      hypoglycemia after acute kidney injury (AKI) is not well defined. The purpose of
      this study was to compare the risk for postdischarge hypoglycemia among
      hospitalized patients with diabetes who do and do not experience AKI. RESEARCH
      DESIGN AND METHODS: We performed a propensity-matched analysis of patients with
      diabetes, with and without AKI, using a retrospective national cohort of veterans
      hospitalized between 2004 and 2012. AKI was defined as a 0.3 mg/dL or 50%
      increase in serum creatinine from baseline to peak serum creatinine during
      hospitalization. Hypoglycemia was defined as hospital admission or an emergency
      department visit for hypoglycemia or as an outpatient blood glucose <60 mg/dL.
      Time to incident hypoglycemia within 90 days postdischarge was examined using Cox
      proportional hazards models. Prespecified subgroup analyses by renal recovery,
      baseline chronic kidney disease, preadmission drug regimen, and HbA1c were
      performed. RESULTS: We identified 65,151 propensity score-matched pairs with and
      without AKI. The incidence of hypoglycemia was 29.6 (95% CI 28.9-30.4) and 23.5
      (95% CI 22.9-24.2) per 100 person-years for patients with and without AKI,
      respectively. After adjustment, AKI was associated with a 27% increased risk of
      hypoglycemia (hazard ratio [HR] 1.27 [95% CI 1.22-1.33]). For patients with full
      recovery, the HR was 1.18 (95% CI 1.12-1.25); for partial recovery, the HR was
      1.30 (95% CI 1.23-1.37); and for no recovery, the HR was 1.48 (95% CI 1.36-1.60)
      compared with patients without AKI. Across all antidiabetes drug regimens,
      patients with AKI experienced hypoglycemia more frequently than patients without
      AKI, though the incidence of hypoglycemia was highest among insulin users,
      followed by glyburide and glipizide users, respectively. CONCLUSIONS: AKI is a
      risk factor for hypoglycemia in the postdischarge period. Studies to identify
      risk-reduction strategies in this population are warranted.

PMID- 29326110
TI  - Contemporary management and outcomes in congenitally corrected transposition of
      the great arteries.
AB  - Congenitally corrected transposition of the great arteries (ccTGA) can occur in
      isolation, or in combination with other structural cardiac anomalies, most
      commonly ventricular septal defect, pulmonary stenosis and tricuspid valve
      disease. Clinical recognition can be challenging, so echocardiography is often
      the means by which definitive diagnosis is made. The tricuspid valve and right
      ventricle are on the systemic arterial side of the ccTGA circulation, and are
      therefore subject to progressive functional deterioration. The natural history of
      ccTGA is also greatly influenced by the nature and severity of accompanying
      lesions, some of which require surgical repair. Some management strategies leave
      the right ventricle as the systemic arterial pump, but carry the risk of
      worsening heart failure. More complex 'double switch' repairs establish the left
      ventricle as the systemic pump, and include an atrial baffle to redirect venous
      return in combination with either arterial switch or Rastelli operation (if a
      suitable ventricular septal defect permits). Occasionally, the anatomic
      peculiarities of ccTGA do not allow straightforward biventricular repair, and
      Fontan palliation is a reasonable option. Regardless of the approach selected,
      late cardiovascular complications are relatively common, so ongoing outpatient
      surveillance should be established in an age-appropriate facility with expertise
      in congenital heart disease care.

PMID- 29326107
TI  - TCF7L2 Genetic Variation Augments Incretin Resistance and Influences Response to
      a Sulfonylurea and Metformin: The Study to Understand the Genetics of the Acute
      Response to Metformin and Glipizide in Humans (SUGAR-MGH).
AB  - OBJECTIVE: The rs7903146 T allele in transcription factor 7 like 2 (TCF7L2) is
      strongly associated with type 2 diabetes (T2D), but the mechanisms for increased
      risk remain unclear. We evaluated the physiologic and hormonal effects of TCF7L2
      genotype before and after interventions that influence glucose physiology.
      RESEARCH DESIGN AND METHODS: We genotyped rs7903146 in 608 individuals without
      diabetes and recorded biochemical data before and after 1) one dose of glipizide
      (5 mg) on visit 1 and 2) a 75-g oral glucose tolerance test (OGTT) performed
      after administration of metformin 500 mg twice daily over 2 days. Incretin levels
      were measured in 150 of the 608 participants. RESULTS: TT risk-allele homozygotes
      had 1.6 mg/dL higher baseline fasting glucose levels and 2.5 pg/mL lower glucagon
      levels per T allele than carriers of other genotypes at baseline. In a subset of
      participants, the T allele was associated with higher basal glucagon-like peptide
      1 (GLP-1) levels at visit 1 (beta = 1.52, P = 0.02 and beta = 0.96, P = 0.002 for
      total and active GLP-1, respectively), and across all points of the OGTT after
      metformin administration. Regarding drug response, the T allele was associated
      with a shorter time (beta = -7.00, P = 0.03) and a steeper slope (beta = 0.23, P
      = 0.04) to trough glucose levels after glipizide administration, and lower visit
      2 fasting glucose level adjusted for visit 1 fasting glucose level (beta = -1.02,
      P = 0.04) and a greater decline in glucose level between visits (beta = -1.61, P
      = 0.047) after metformin administration. CONCLUSIONS: Our findings demonstrate
      that common variation at TCF7L2 influences acute responses to both glipizide and
      metformin in people without diabetes and highlight altered incretin signaling as
      a potential mechanism by which TCF7L2 variation increases T2D risk.

PMID- 29326112
TI  - Epidemiology of new-onset atrial fibrillation following coronary artery bypass
      graft surgery.
AB  - OBJECTIVES: Postoperative atrial fibrillation (AF) following coronary artery
      bypass graft surgery (CABG) is significantly associated with reduced survival,
      but poor characterisation and inconsistent definitions present barriers to
      developing effective prophylaxis and management. We sought to address this
      knowledge gap. METHODS: From 2002 to 2010, 11 239 consecutive patients without AF
      underwent isolated CABG at five sites. Clinical data collected for the Society of
      Thoracic Surgeons (STS) Database were augmented with details on AF detected via
      continuous in-hospital ECG/telemetry monitoring to assess new-onset post-CABG AF
      (adjusted for STS risk of mortality); time to first AF; durations of first and
      longest AF episodes; total in-hospital time in AF; number of in-hospital AF
      episodes; operative mortality; stroke; discharge in AF; and length of stay (LOS).
      RESULTS: Unadjusted incidence of new-onset post-CABG AF was 29.5%. Risk-adjusted
      incidence was 33.1% and varied little over time (P=0.139). Among 3312 patients
      with post-CABG AF, adjusted median time to first AF was 52 (IQR: 48-55) hours;
      mean (SD) duration of first and longest events were 7.2 (5.3,9.1) and 13.1
      (10.4,15.9) hours, respectively, and adjusted median total time in AF was 22
      (IQR: 18-26) hours. Adjusted rates of operative mortality, stroke and discharge
      in AF did not vary significantly over time (P=0.156, P=0.965 and P=0.347,
      respectively). LOS varied (P=0.035), but in no discernible pattern. CONCLUSIONS:
      Each year, ~800 000 people undergo CABG worldwide; >264 000 will develop post
      CABG AF. Onset is typically 2-3 days post-CABG and episodes last, on average,
      several hours. Effective prophylaxis and management is urgently needed to reduce
      associated risks of adverse outcomes.

PMID- 29326113
TI  - Acute heart failure with new-onset continuous murmur in a 26-year-old man.

PMID- 29326111
TI  - Low prevalence of ideal cardiovascular health in Peru.
AB  - BACKGROUND: The prevalence of and factors associated with ideal cardiovascular
      health (ICH) by sociodemographic characteristics in Peru is not well known.
      METHODS: The American Heart Association's ICH score comprised 3 ideal health
      factors (blood pressure, untreated total cholesterol and glucose) and 4 ideal
      health behaviours (smoking, body mass index, high physical activity and fruit and
      vegetable consumption). ICH was having 5 to 7 of the ideal health metrics.
      Baseline data from the Center of Excellence in Chronic Diseases, a prospective
      cohort study in adults aged >=35 years in 4 Peruvian settings, was used (n=3058).
      RESULTS: No one met all 7 of ICH metrics while 322 (10.5%) had <=1 metric.
      Fasting plasma glucose was the most prevalent health factor (72%). Overall,
      compared with ages 35-44 years, the 55-64 years age group was associated with a
      lower prevalence of ICH (prevalence ratio 0.54, 95% CI 0.40 to 0.74, P<0.001).
      Compared with those in the lowest tertile of socioeconomic status, those in the
      middle and highest tertiles were less likely to have ICH after adjusting for sex,
      age and education (P<0.001). CONCLUSION: There is a low prevalence of ICH. This
      is a benchmark for the prevalence of ICH factors and behaviours in a resource
      poor setting.

PMID- 29326114
TI  - Biomechanics of swimming in developing larval fish.
AB  - Most larvae of bony fish are able to swim almost immediately after hatching.
      Their locomotory system supports several vital functions: fish larvae make fast
      manoeuvres to escape from predators, aim accurately during suction feeding and
      may migrate towards suitable future habitats. Owing to their small size and low
      swimming speed, larval fish operate in the intermediate hydrodynamic regime,
      which connects the viscous and inertial flow regimes. They experience relatively
      strong viscous effects at low swimming speeds, and relatively strong inertial
      effects at their highest speeds. As the larvae grow and increase swimming speed,
      a shift occurs towards the inertial flow regime. To compensate for size-related
      limitations on swimming speed, fish larvae exploit high tail beat frequencies at
      their highest speeds, made possible by their low body inertia and fast
      neuromuscular system. The shifts in flow regime and body inertia lead to changing
      functional demands on the locomotory system during larval growth. To reach the
      reproductive adult stage, the developing larvae need to adjust to and perform the
      functions necessary for survival. Just after hatching, many fish larvae rely on
      yolk and need to develop their feeding systems before the yolk is exhausted.
      Furthermore, the larvae need to develop and continuously adjust their sensory,
      neural and muscular systems to catch prey and avoid predation. This Review
      discusses the hydrodynamics of swimming in the intermediate flow regime, the
      changing functional demands on the locomotory system of the growing and
      developing larval fish, and the solutions that have evolved to accommodate these
      demands.

PMID- 29326115
TI  - Understanding variation in metabolic rate.
AB  - Metabolic rate reflects an organism's capacity for growth, maintenance and
      reproduction, and is likely to be a target of selection. Physiologists have long
      sought to understand the causes and consequences of within-individual to among
      species variation in metabolic rates - how metabolic rates relate to performance
      and how they should evolve. Traditionally, this has been viewed from a
      mechanistic perspective, relying primarily on hypothesis-driven approaches. A
      more agnostic, but ultimately more powerful tool for understanding the dynamics
      of phenotypic variation is through use of the breeder's equation, because
      variation in metabolic rate is likely to be a consequence of underlying
      microevolutionary processes. Here we show that metabolic rates are often
      significantly heritable, and are therefore free to evolve under selection. We
      note, however, that 'metabolic rate' is not a single trait: in addition to the
      obvious differences between metabolic levels (e.g. basal, resting, free-living,
      maximal), metabolic rate changes through ontogeny and in response to a range of
      extrinsic factors, and is therefore subject to multivariate constraint and
      selection. We emphasize three key advantages of studying metabolic rate within a
      quantitative genetics framework: its formalism, and its predictive and
      comparative power. We make several recommendations when applying a quantitative
      genetics framework: (i) measuring selection based on actual fitness, rather than
      proxies for fitness; (ii) considering the genetic covariances between metabolic
      rates throughout ontogeny; and (iii) estimating genetic covariances between
      metabolic rates and other traits. A quantitative genetics framework provides the
      means for quantifying the evolutionary potential of metabolic rate and why
      variance in metabolic rates within populations might be maintained.

PMID- 29326116
TI  - Behavioural responses to infrasonic particle acceleration in cuttlefish.
AB  - Attacks by aquatic predators generate frontal water disturbances characterised by
      low-frequency gradients in pressure and particle motion. Low-frequency hearing is
      highly developed in cephalopods. Thus, we examined behavioural responses in
      juvenile cuttlefish to infrasonic accelerations mimicking main aspects of the
      hydrodynamic signals created by predators. In the experimental set-up, animals
      and their surrounding water moved as a unit to minimise lateral line activation
      and to allow examination of the contribution by the inner ear. Behavioural
      responses were tested in light versus darkness and after food deprivation
      following a 'simulated' hunting opportunity. At low acceleration levels, colour
      change threshold at 3, 5 and 9 Hz was 0.028, 0.038 and 0.035 m s-2, respectively.
      At higher stimulus levels, jet-propulsed escape responses thresholds in daylight
      were 0.043, 0.065 and 0.069 m s-2 at 3, 5 and 9 Hz, respectively, and not
      significantly different from the corresponding darkness thresholds of 0.043,
      0.071 and 0.064 m s-2 In a simulated hunting mode, escape thresholds were
      significantly higher at 3 Hz (0.118 m s-2) but not at 9 Hz (0.134 m s-2). Escape
      responses were directional, and overall followed the direction of the initial
      particle acceleration, with mean escape angles from 313 to 33 deg for all three
      experiments. Thus, in the wild, particle acceleration might cause escape
      responses directed away from striking predators but towards suction-feeding
      predators. We suggest that cuttlefish jet-propulsed escape behaviour has evolved
      to be elicited by the early hydrodynamic disturbances generated during predator
      encounters, and that the inner ear plays an essential role in the acoustic escape
      responses.

PMID- 29326117
TI  - Ideal Weyl points and helicoid surface states in artificial photonic crystal
      structures.
AB  - Weyl points are the crossings of linearly dispersing energy bands of three
      dimensional crystals, providing the opportunity to explore a variety of
      intriguing phenomena such as topologically protected surface states and chiral
      anomalies. However, the lack of an ideal Weyl system in which the Weyl points all
      exist at the same energy and are separated from any other bands poses a serious
      limitation to the further development of Weyl physics and potential applications.
      By experimentally characterizing a microwave photonic crystal of saddle-shaped
      metallic coils, we observed ideal Weyl points that are related to each other
      through symmetry operations. Topological surface states exhibiting helicoidal
      structure have also been demonstrated. Our system provides a photonic platform
      for exploring ideal Weyl systems and developing possible topological devices.

PMID- 29326118
TI  - Observation of bulk Fermi arc and polarization half charge from paired
      exceptional points.
AB  - The ideas of topology have found tremendous success in closed physical systems,
      but even richer properties exist in the more general open or dissipative
      framework. We theoretically propose and experimentally demonstrate a bulk Fermi
      arc that develops from non-Hermitian radiative losses in an open system of
      photonic crystal slabs. Moreover, we discover half-integer topological charges in
      the polarization of far-field radiation around the bulk Fermi arc. Both phenomena
      are shown to be direct consequences of the non-Hermitian topological properties
      of exceptional points, where resonances coincide in their frequencies and
      linewidths. Our work connects the fields of topological photonics, non-Hermitian
      physics, and singular optics, providing a framework to explore more complex non
      Hermitian topological systems.

PMID- 29326119
TI  - Association of mutations with morphological dysplasia in de novo acute myeloid
      leukemia without 2016 WHO Classification-defined cytogenetic abnormalities.
AB  - Despite improvements in our understanding of the molecular basis of acute myeloid
      leukemia (AML), the association between genetic mutations with morphological
      dysplasia remains unclear. In this study, we evaluated and scored dysplasia in
      bone marrow (BM) specimens from 168 patients with de novo AML; none of these
      patients had cytogenetic abnormalities according to the 2016 World Health
      Organization Classification. We then performed targeted sequencing of diagnostic
      BM aspirates for recurrent mutations associated with myeloid malignancies. We
      found that cohesin pathway mutations [q (FDR-adjusted P)=0.046] were associated
      with a higher degree of megakaryocytic dysplasia and STAG2 mutations were
      marginally associated with greater myeloid lineage dysplasia (q=0.052). Frequent
      megakaryocytes with separated nuclear lobes were more commonly seen among cases
      with cohesin pathway mutations (q=0.010) and specifically in those with STAG2
      mutations (q=0.010), as well as NPM1 mutations (q=0.022 when considering the
      presence of any vs no megakaryocytes with separated nuclear lobes). RAS pathway
      mutations (q=0.006) and FLT3-ITD (q=0.006) were significantly more frequent in
      cases without evaluable erythroid cells. In univariate analysis of the 153
      patients treated with induction chemotherapy, NPM1 mutations were associated with
      longer event-free survival (EFS) (P=0.042), while RUNX1 (P=0.042), NF1 (P=0.040),
      frequent micromegakaryocytes (P=0.018) and presence of a subclone (P=0.002) were
      associated with shorter EFS. In multivariable modeling, NPM1 was associated with
      longer EFS, while presence of a subclone and frequent micromegakaryocytes
      remained significantly associated with shorter EFS.

PMID- 29326120
TI  - Macrophage scavenger receptor SR-AI contributes to the clearance of von
      Willebrand factor.
AB  - Previously, we found that LDL-receptor related protein-1 on macrophages mediated
      shear stress-dependent clearance of von Willebrand factor. In control
      experiments, however, we observed that von Willebrand factor also binds to
      macrophages independently of this receptor under static conditions, suggesting
      the existence of additional clearance-receptors. In search for such receptors, we
      focused on the macrophage-specific scavenger-receptor SR-AI. von Willebrand
      factor displays efficient binding to SR-AI (half-maximum binding 14+/-5 nM).
      Binding is calcium-dependent and is inhibited by 72+/-4% in the combined presence
      of antibodies against the A1- and D4-domains. Association with SR-AI was
      confirmed in cell-binding experiments. In addition, binding to bone marrow
      derived murine SR-AI-deficient macrophages was strongly reduced compared to
      binding to wild-type murine macrophages. Following expression via hydrodynamic
      gene transfer, we determined ratios for von Willebrand factor-propeptide over von
      Willebrand factor-antigen, a marker of von Willebrand factor clearance.
      Propeptide/antigen ratios were significantly reduced in SR-AI-deficient mice
      compared to wild-type mice (0.6+/-0.2 versus 1.3+/-0.3; P<0.0001), compatible
      with a slower clearance of von Willebrand factor in SR-AI-deficient mice.
      Interestingly, mutants associated with increased clearance (von Willebrand
      factor/p.R1205H and von Willebrand factor/p.S2179F) had significantly increased
      binding to purified SR-AI and SR-AI expressed on macrophages. Accordingly,
      propeptide/antigen ratios for these mutants were reduced in SR-AI-deficient mice.
      In conclusion, we have identified SR-AI as a novel macrophage-specific receptor
      for von Willebrand factor. Enhanced binding of von Willebrand factor mutants to
      SR-AI may contribute to the increased clearance of these mutants.

PMID- 29326121
TI  - Modeling multiple myeloma-bone marrow interactions and response to drugs in a 3D
      surrogate microenvironment.
AB  - Multiple myeloma develops primarily inside the bone marrow microenvironment, that
      confers pro-survival signals and drug resistance. 3D cultures that reproduce
      multiple myeloma-bone marrow interactions are needed to fully investigate
      multiple myeloma pathogenesis and response to drugs. To this purpose, we
      exploited the 3D Rotary Cell Culture System bioreactor technology for myeloma
      bone marrow co-cultures in gelatin scaffolds. The model was validated with
      myeloma cell lines that, as assessed by histochemical and electron-microscopic
      analyses, engaged contacts with stromal cells and endothelial cells.
      Consistently, pro-survival signaling and also cell adhesion-mediated drug
      resistance were significantly higher in 3D than in 2D parallel co-cultures. The
      contribution of the VLA-4/VCAM1 pathway to resistance to bortezomib was modeled
      by the use of VCAM1 transfectants. Soluble factor-mediated drug resistance could
      be also demonstrated in both 2D and 3D co-cultures. The system was then
      successfully applied to co-cultures of primary myeloma cells-primary myeloma bone
      marrow stromal cells from patients and endothelial cells, allowing the
      development of functional myeloma-stroma interactions and MM cell long-term
      survival. Significantly, genomic analysis performed in a high-risk myeloma
      patient demonstrated that culture in bioreactor paralleled the expansion of the
      clone that ultimately dominated in vivo Finally, the impact of bortezomib on
      myeloma cells and on specialized functions of the microenvironment could be
      evaluated. Our findings indicate that 3D dynamic culture of reconstructed human
      multiple myeloma microenvironments in bioreactor may represent a useful platform
      for drug testing and for studying tumor-stroma molecular interactions.

PMID- 29326122
TI  - Gfi1b: a key player in the genesis and maintenance of acute myeloid leukemia and
      myelodysplastic syndrome.
AB  - Differentiation of hematopoietic stem cells is regulated by a concert of
      different transcription factors. Disturbed transcription factor function can be
      the basis of (pre)malignancies such as myelodysplastic syndrome (MDS) or acute
      myeloid leukemia (AML). Growth factor independence 1b (Gfi1b) is a repressing
      transcription factor regulating quiescence of hematopoietic stem cells and
      differentiation of erythrocytes and platelets. Here, we show that low expression
      of Gfi1b in blast cells is associated with an inferior prognosis of MDS and AML
      patients. Using different models of human MDS or AML, we demonstrate that AML
      development was accelerated with heterozygous loss of Gfi1b, and latency was
      further decreased when Gfi1b was conditionally deleted. Loss of Gfi1b
      significantly increased the number of leukemic stem cells with upregulation of
      genes involved in leukemia development. On a molecular level, we found that loss
      of Gfi1b led to epigenetic changes, increased levels of reactive oxygen species,
      as well as alteration in the p38/Akt/FoXO pathways. These results demonstrate
      that Gfi1b functions as an oncosuppressor in MDS and AML development.

PMID- 29326125
TI  - Hazardous alcohol consumption among spouses or partners of military service
      personnel: a systematic review of the literature.
AB  - BACKGROUND: Alcohol misuse is particularly high among both the UK and US Armed
      Forces. As alcohol use among couples is associated, military spouses or partners
      may therefore be at a higher risk of acquiring hazardous drinking behaviours than
      people in relationships with other occupational groups. METHOD: A literature
      review using a systematic approach was undertaken in four medical databases and
      supplemented with hand searches of specialist publications and reference lists.
      The prevalence of hazardous alcohol consumption among military spouses or
      partners was estimated and potential sociodemographic and military factors
      associated with this outcome were identified. RESULTS: Nine papers met inclusion
      criteria, of which eight focused on female spouses or partners only. The limited
      evidence suggests hazardous alcohol consumption was not a common outcome among
      spouses or partners. None of the papers statistically compared the prevalence
      among spouses or partners to estimates from the general population and few
      reported associations with sociodemographic or military factors. Deployment
      abroad did not appear to be significantly associated with hazardous consumption,
      although increasing periods of separation from Service personnel may be
      associated with increased hazardous consumption among spouses or partners.
      CONCLUSION: Limited evidence was found concerning the prevalence of hazardous
      alcohol consumption among military spouses or partners or which sociodemographic
      and military factors might be associated with this outcome. The a dominance of US
      studies means applying the estimates of these outcomes to other nations must be
      undertaken with care due to differences in cultural attitudes to alcohol as well
      as differences between military structure and operations between the US and other
      nations.

PMID- 29326123
TI  - Tumor necrosis factor receptor signaling is a driver of chronic lymphocytic
      leukemia that can be therapeutically targeted by the flavonoid wogonin.
AB  - Chronic lymphocytic leukemia is a malignancy of mature B cells that strongly
      depend on microenvironmental factors, and their deprivation has been identified
      as a promising treatment approach for this incurable disease. Cytokine array
      screening of 247 chronic lymphocytic leukemia serum samples revealed elevated
      levels of tumor necrosis factor (TNF) receptor-1 which were associated with poor
      clinical outcome. We detected a microenvironment-induced expression of TNF
      receptor-1 in chronic lymphocytic leukemia cells in vitro, and an aberrantly high
      expression of this receptor in the proliferation centers of patients' lymph
      nodes. Stimulation of TNF receptor-1 with TNF-alpha enhanced nuclear factor kappa
      light-chain-enhancer of activated B cells (NFkappaB) activity and viability of
      chronic lymphocytic leukemia cells, which was inhibited by wogonin. The
      therapeutic effects of wogonin were analyzed in mice after adoptive transfer of
      EMU-T-cell leukemia 1 (TCL1) leukemic cells. Wogonin treatment prevented leukemia
      development when given early after transplantation. The treatment of full-blown
      leukemia resulted in the loss of the TNF receptor-1 on chronic lymphocytic
      leukemia cells and their mobilization to blood. Targeting TNF receptor-1
      signaling is therefore proposed for the treatment of chronic lymphocytic
      leukemia.

PMID- 29326124
TI  - Bortezomib-based immunosuppression after reduced-intensity conditioning
      hematopoietic stem cell transplantation: randomized phase II results.
AB  - Aprior phase I/II trial of bortezomib/tacrolimus/methotrexate prophylaxis after
      human leukocyte antigen (HLA)-mismatched reduced intensity conditioning
      allogeneic hematopoietic stem cell transplantation documented low acute graft
      versus-host disease incidence, with promising overall and progression-free
      survival. We performed an open-label three-arm 1:1:1 phase II randomized
      controlled trial comparing grade II-IV acute graft-versus-host disease between
      conventional tacrolimus/methotrexate (A) versus
      bortezomib/tacrolimus/methotrexate (B), and versus
      bortezomib/sirolimus/tacrolimus (C), in reduced intensity conditioning allogeneic
      transplantation recipients lacking HLA-matched related donors. The primary
      endpoint was grade II-IV acute graft-versus-host disease incidence rate by day
      +180. One hundred and thirty-eight patients (A 46, B 45, C 47) with a median age
      of 64 years (range: 24-75), varying malignant diagnoses and disease risk (low 14,
      intermediate 96, high/very high 28) received 7-8/8 HLA-mismatched (40) or matched
      unrelated donor (98) grafts. Median follow up in survivors was 30 months (range:
      14-46). Despite early immune reconstitution differences, day +180 grade II-IV
      acute graft-versus-host disease rates were similar (A 32.6%, B 31.1%, C 21%;
      P=0.53 for A vs B, P=0.16 for A vs C). The 2-year non-relapse mortality incidence
      was similar (A 14%, B 16%, C 6.4%; P=0.62), as were relapse (A 32%, B 32%, C 38%;
      P=0.74), chronic graft-versus-host disease (A 59%, B 60% C 55%; P=0.66),
      progression-free survival (A 54%, B 52%, C 55%; P=0.95), and overall survival (A
      61%, B 62%, C 62%; P=0.98). Overall, the bortezomib-based regimens evaluated did
      not improve outcomes compared with tacrolimus/methotrexate therapy.
      clinicaltrials.gov Identifier: 01754389.

PMID- 29326126
TI  - One hundred years (and counting) of blast-associated traumatic brain injury.
AB  - Blast-associated traumatic brain injury (TBI) has become one of the signature
      issues of modern warfare and is increasingly a concern in the civilian population
      due to a rise in terrorist attacks. Despite being a recognised feature of combat
      since the introduction of high explosives in conventional warfare over a century
      ago, only recently has there been interest in understanding the biology and
      pathology of blast TBI and the potential long-term consequences. Progress made
      has been slow and there remain remarkably few robust human neuropathology studies
      in this field. This article provides a broad overview of the history of blast TBI
      and reviews the pathology described in the limitedscientific studies found in the
      literature.

PMID- 29326127
TI  - Skill sets required for the management of military head, face and neck trauma: a
      multidisciplinary consensus statement.
AB  - INTRODUCTION: The evolution of medical practice is resulting in increasing
      subspecialisation, with head, face and neck (HFN) trauma in a civilian
      environment usually managed by a combination of surgical specialties working as a
      team. However, the full combination of HFN specialties commonly available in the
      NHS may not be available in future UK military-led operations, necessitating the
      identification of a group of skill sets that could be delivered by one or more
      deployed surgeons. METHOD: A systematic review was undertaken to identify those
      surgical procedures performed to treat acute military head, face, neck and eye
      trauma. A multidisciplinary consensus group was convened following this with
      military HFN trauma expertise to define those procedures commonly required to
      conduct deployed, in-theatre HFN surgical combat trauma management. RESULTS:
      Head, face, neck and eye damage control surgical procedures were identified as
      comprising surgical cricothyroidotomy, cervico-facial haemorrhage control and
      decompression of orbital haemorrhage through lateral canthotomy. Acute in-theatre
      surgical skills required within 24 hours consist of wound debridement, surgical
      tracheostomy, decompressive craniectomy, intracranial pressure monitor placement,
      temporary facial fracture stabilisation for airway management or haemorrhage
      control and primary globe repair. Delayed in-theatre procedures required within 5
      days prior to predicted evacuation encompass facial fracture fixation, delayed
      lateral canthotomy, evisceration, enucleation and eyelid repair. CONCLUSIONS: The
      identification of those skill sets required for deployment is in keeping with the
      General Medical Council's current drive towards credentialing consultants, by
      which a consultant surgeon's capabilities in particular practice areas would be
      defined. Limited opportunities currently exist for trainees and consultants to
      gain experience in the management of traumatic head, face, neck and eye injuries
      seen in a kinetic combat environment. Predeployment training requires that the
      surgical techniques described in this paper are covered and should form the
      curriculum of future military-specific surgical fellowships. Relevant continued
      professional development will be necessary to maintain required clinical
      competency.

PMID- 29326128
TI  - Idiopathic Ventricular Arrhythmias Originating From the Vicinity of the
      Communicating Vein of Cardiac Venous Systems at the Left Ventricular Summit.
AB  - BACKGROUND: The communicating vein (CV) between the great cardiac vein and small
      cardiac venous systems passes between the aortic and pulmonary annulus and is
      located in close association with the left ventricular summit (summit CV).
      METHODS AND RESULTS: Thirty-one patients with idiopathic ventricular arrhythmias
      (VAs) underwent mapping of the left ventricular summit by using a 2F
      microcatheter introduced into the summit CV with coronary sinus venographic
      guidance. Of these, 14 patients were found to have summit-CV VAs. The remaining
      17 patients (control group) had VAs originating from the right ventricular
      outflow tract and the aortic cusps. In patients with summit-CV VAs, the earliest
      activation during VAs in the summit CV preceded QRS onset by 34.1+/-5.3 ms. The
      summit-CV VAs exhibited inferior axis, negative polarity in lead I, deeper QS
      wave in lead aVL than aVR, and nonspecific bundle branch block morphology with an
      R/S ratio in lead V1 of 0.67+/-0.33, which could be distinguishable from VAs
      originating from the right ventricular outflow tract and the right coronary cusp.
      Because of the inaccessibility of the summit CV to ablation catheter, ablation of
      summit-CV VAs was attempted at adjacent structures where an excellent pacemap was
      rarely obtained. Overall ablation success was achieved in 10 (71%) patients with
      summit VAs and 15 (88%) patients in control group (P=0.24). CONCLUSIONS: The
      myocardium near the summit CV can be the source of idiopathic VAs. Direct
      monitoring of the summit CV is helpful for identifying the site of origin and
      provides a landmark of the ablation target, which may facilitate ablation through
      adjacent structures.

PMID- 29326129
TI  - Machine Learning Algorithm Predicts Cardiac Resynchronization Therapy Outcomes:
      Lessons From the COMPANION Trial.
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) reduces morbidity and
      mortality in heart failure patients with reduced left ventricular function and
      intraventricular conduction delay. However, individual outcomes vary
      significantly. This study sought to use a machine learning algorithm to develop a
      model to predict outcomes after CRT. METHODS AND RESULTS: Models were developed
      with machine learning algorithms to predict all-cause mortality or heart failure
      hospitalization at 12 months post-CRT in the COMPANION trial (Comparison of
      Medical Therapy, Pacing, and Defibrillation in Heart Failure). The best
      performing model was developed with the random forest algorithm. The ability of
      this model to predict all-cause mortality or heart failure hospitalization and
      all-cause mortality alone was compared with discrimination obtained using a
      combination of bundle branch block morphology and QRS duration. In the 595
      patients with CRT-defibrillator in the COMPANION trial, 105 deaths occurred
      (median follow-up, 15.7 months). The survival difference across subgroups
      differentiated by bundle branch block morphology and QRS duration did not reach
      significance (P=0.08). The random forest model produced quartiles of patients
      with an 8-fold difference in survival between those with the highest and lowest
      predicted probability for events (hazard ratio, 7.96; P<0.0001). The model also
      discriminated the risk of the composite end point of all-cause mortality or heart
      failure hospitalization better than subgroups based on bundle branch block
      morphology and QRS duration. CONCLUSIONS: In the COMPANION trial, a machine
      learning algorithm produced a model that predicted clinical outcomes after CRT.
      Applied before device implant, this model may better differentiate outcomes over
      current clinical discriminators and improve shared decision-making with patients.

PMID- 29326131
TI  - Computer Modeling: The Future of Cardiac Resynchronization Therapy Patient
      Selection?

PMID- 29326130
TI  - Inward Rectifier Potassium Channels (Kir2.x) and Caveolin-3 Domain-Specific
      Interaction: Implications for Purkinje Cell-Dependent Ventricular Arrhythmias.
AB  - BACKGROUND: In human cardiac ventricle, IK1 is mainly comprised Kir2.1, but
      Kir2.2 and Kir2.3 heterotetramers occur and modulate IK1. Long-QT syndrome-9
      associated CAV3 mutations cause decreased Kir2.1 current density, but Kir2.x
      heterotetramers have not been studied. Here, we determine the effect of long-QT
      syndrome-9-CAV3 mutation F97C on Kir2.x homo- and heterotetramers and model
      associated arrhythmia mechanisms. METHODS AND RESULTS: Super-resolution
      microscopy, co-immunoprecipitation, cellular electrophysiology, on-cell Western
      blotting, and simulation of Purkinje and ventricular myocyte mathematical models
      were used. Kir2.x isoforms have unique subcellular colocalization in human
      cardiomyocytes and coimmunoprecipitate with Cav3. F97C-Cav3 decreased peak inward
      Kir2.2 current density by 50% (-120 mV; P=0.019) and peak outward by 75% (-40 mV;
      P<0.05) but did not affect Kir2.3 current density. FRET (Forster resonance energy
      transfer) efficiency for Kir2.2 with Cav3 is high, and on-cell Western blotting
      demonstrates decreased Kir2.2 membrane expression with F97C-Cav3. Cav3-F97C
      reduced peak inward and outward current density of Kir2.2/Kir2.1 or Kir2.2/Kir2.3
      heterotetramers (P<0.05). Only Cav3 scaffolding and membrane domains co
      immunoprecipitation with Kir2.1 and Kir2.2 and Kir2.x-N-terminal Cav3 binding
      motifs are required for interaction. Mathematical Purkinje, but not ventricular,
      myocyte model incorporating simulated current reductions, predicts spontaneous
      delayed after-depolarization-mediated triggered activity. CONCLUSIONS: Kir2.x
      isoforms have a unique intracellular pattern of distribution in association with
      specific Cav3 domains and that critically depends on interaction with N-terminal
      Kir2.x Cav3-binding motifs. Long-QT syndrome-9-CAV3 mutation differentially
      regulates current density and cell surface expression of Kir2.x homomeric and
      heteromeric channels. Mathematical Purkinje cell model incorporating experimental
      findings suggests delayed after-depolarization-type triggered activity as a
      possible arrhythmia mechanism.

PMID- 29326132
TI  - Ventricular Arrhythmias Linked to the Left Ventricular Summit Communicating
      Veins: A New Mapping Approach for an Old Ablation Problem.

PMID- 29326134
TI  - Evaluation of estrogenic potential by herbal formula, HPC 03 for in vitro and in
      vivo.
AB  - HPC 03 is herbal formula that consists of extracts from Angelica gigas, Cnidium
      officinale Makino and Cinnamomum cassia Presl. The present study evaluated the
      estrogenic potential of HPC 03 by using in vitro and in vivo models. The
      regulatory mechanisms of HPC 03 in estrogen-dependent MCF-7 cells were assessed.
      HPC 03 induced the proliferation of estrogen receptor-positive MCF-7 cells, and
      the proliferation was blocked by the addition of the estrogen antagonist
      tamoxifen. The estrogen receptoralpha/beta luciferase activities were
      significantly increased by HPC 03 treatment, which also increased the mRNA
      expression of the estrogen-responsive genes Psen2, Pgr and Ctsd Also, we
      evaluated the ameliorative effects of HPC 03 on menopausal symptoms in
      ovariectomized rats. HPC 03 treatment in OVX rats significantly affected the
      uterine weight, increased the expression of estrogen-responsive genes Pgr and
      Psen2 in uterus, increased bone mineral density loss in the femur and inhibited
      body weight increase. Serum E2, collagen type 1 and osteocalcin were
      significantly increased, while serum LH, FSH and ALP were decreased compared with
      OVX rats. HPC 03 may be a promising candidate for the treatment of menopause, but
      further research is necessary to determine whether the observed effects also
      occur in humans.

PMID- 29326136
TI  - Using Correlative Properties of Neighboring Pixels to Improve Gray-White
      Differentiation in Pediatric Head CT Images.
AB  - BACKGROUND AND PURPOSE: A lower radiation dose can have a detrimental effect on
      the quality of head CT images. The aim of this study performed in a pediatric
      population was to test whether an image-processing algorithm (Correlative Image
      Enhancement) based on the correlation among intensities of neighboring pixels can
      improve gray-white differentiation in head CTs. MATERIALS AND METHODS: Sixty
      baseline head CT images with normal findings obtained from scans of 30 children
      were processed using Correlative Image Enhancement to produce corresponding
      enhanced images. Gray-white differentiation in baseline and enhanced images was
      assessed quantitatively by calculating the contrast-to-noise ratio and
      conspicuity in equivalent ROIs in gray and white matter. Two masked readers rated
      the images for visibility of gray-white differentiation on a 5-point Likert
      scale. Differences in both quantitative and qualitative measures of gray-white
      differentiation between baseline and enhanced images were tested for statistical
      significance. P values < .05 were considered significant. RESULTS: Image
      processing resulted in improvement in the contrast-to-noise ratio (from 1.86 +/-
      0.94 to 2.26 +/- 1.00, P = .02) as well as conspicuity (from 37.28 +/- 11.56 to
      46.4 +/- 11.5, P < .001). This was accompanied by improved subjective visibility
      of gray-white differentiation as reported by both readers (P < .01). CONCLUSIONS:
      Image processing using Correlative Image Enhancement had a beneficial effect on
      quantitative measures of gray-white differentiation. This translated into
      improved perception of gray-white differentiation by readers. Further studies are
      needed to assess the effect of such image processing on the detection of disease
      processes using head CTs.

PMID- 29326135
TI  - Isolation of human testicular cells and co-culture with embryonic stem cells.
AB  - Our overall goal is to create a three-dimensional human cell-based testicular
      model for toxicological and spermatogenesis studies. Methods to purify the major
      somatic testicular cells, namely Leydig cells (LCs), peritubular myoid cells
      (PCs) and Sertoli cells (SCs), from rats, mice and guinea pigs have been
      reported. In humans, the isolation of populations enriched for primary LCs, PCs
      or SCs also have described. One objective of this study was to determine if
      populations of cells enriched for all three of these cell types can be isolated
      from testes of single human donors, and we were successful in doing so from
      testes of three donors. Testes tissues were enzymatically digested, gravity
      sedimented and Percoll filtered to isolate populations enriched for LCs, PCs and
      SCs. LCs and PCs were identified by colorimetric detection of the expression of
      prototypical enzymes. Division of PCs and SCs in culture has been reported. We
      observed that primary human LCs could divide in culture by incorporation of 5
      ethynyl-2'-deoxyuridine. SCs were identified and their functionality was
      demonstrated by the formation of tight junctions as shown by the expression of
      tight junction proteins, increased transepithelial electrical resistance,
      polarized secretion of biomolecules and inhibition of lucifer yellow penetration.
      Furthermore, we found that human SC feeder layers could facilitate germ cell
      progression of human embryonic stem cells (hESCs) by microarray analysis of gene
      expression.

PMID- 29326137
TI  - Expression Changes in Lactate and Glucose Metabolism and Associated Transporters
      in Basal Ganglia following Hypoxic-Ischemic Reperfusion Injury in Piglets.
AB  - BACKGROUND AND PURPOSE: The neonatal brain has active energy metabolism, and
      glucose oxidation is the major energy source of brain tissue. Lactate is produced
      by astrocytes and released to neurons. In the central nervous system, lactate is
      transported between neurons and astrocytes via the astrocyte-neuron lactate
      shuttle. The aim of this study was to investigate the regulatory mechanisms of
      energy metabolism in neurons and astrocytes in the basal ganglia of a neonatal
      hypoxic-ischemic brain injury piglet model. MATERIALS AND METHODS: A total of 35
      healthy piglets (3-5 days of age; 1.0-1.5 kg) were assigned to a control group (n
      = 5) or a hypoxic-ischemic model group (n = 30). The hypoxic-ischemic model group
      was further divided into 6 groups according to the 1H-MR spectroscopy and PET/CT
      scan times after hypoxia-ischemia (0-2, 2-6, 6-12, 12-24, 24-48, and 48-72 hours;
      n = 5/group). 1H-MR spectroscopy data were processed with LCModel software.
      Maximum standard uptake values refer to the maximum standard uptake values for
      glucose (or FDG). The maximum standard uptake values of the basal ganglia-to
      occipital cortex ratio were analyzed. The expression levels of glucose
      transporters and monocarboxylate transporters were detected by
      immunohistochemical analysis. RESULTS: Lactate levels decreased after an initial
      increase, with the maximal level occurring around 2-6 hours following hypoxia
      ischemia. After hypoxia-ischemia, the maximum standard uptake values of the basal
      ganglia and basal ganglia/occipital cortex initially increased then decreased,
      with the maximum occurring at approximately 6-12 hours. The lactate and glucose
      uptake (basal ganglia/occipital cortex maximum standard uptake values) levels
      were positively correlated. The expression levels of glucose transporter-1 and
      glucose transporter-3 were positively correlated with the basal ganglia/occipital
      cortex. The expression levels of monocarboxylic acid transporter-2 and
      monocarboxylic acid transporter-4 were positively correlated with lactate
      content. CONCLUSIONS: The results indicate that lactate and glucose transporters
      have a synergistic effect on the energy metabolism of neurons and astrocytes
      following hypoxic-ischemic reperfusion brain injury.

PMID- 29326133
TI  - Lipid signaling to membrane proteins: From second messengers to membrane domains
      and adapter-free endocytosis.
AB  - Lipids influence powerfully the function of ion channels and transporters in two
      well-documented ways. A few lipids act as bona fide second messengers by binding
      to specific sites that control channel and transporter gating. Other lipids act
      nonspecifically by modifying the physical environment of channels and
      transporters, in particular the protein-membrane interface. In this short review,
      we first consider lipid signaling from this traditional viewpoint, highlighting
      innumerable Journal of General Physiology publications that have contributed to
      our present understanding. We then switch to our own emerging view that much
      important lipid signaling occurs via the formation of membrane domains that
      influence the function of channels and transporters within them, promote selected
      protein-protein interactions, and control the turnover of surface membrane.

PMID- 29326138
TI  - Cerebellar Hypoperfusion in Migraine Attack: Incidence and Significance.
AB  - BACKGROUND AND PURPOSE: Patients diagnosed with migraine with aura have an
      increased lifetime risk of ischemic stroke. It is not yet clear whether prolonged
      cortical hypoperfusion during an aura increases the immediate risk of cerebellar
      infarction because it may induce crossed cerebellar diaschisis and subsequent
      tissue damage. To address this question, we retrospectively analyzed potential
      relationships between cortical oligemia and cerebellar hypoperfusion in patients
      with migraine with aura and their potential relation to small infarct-like
      cerebellar lesions. MATERIALS AND METHODS: One hundred six migraineurs who
      underwent MR imaging, including DSC perfusion, were included in the study. In
      patients with apparent perfusion asymmetry, we used ROI analysis encompassing 18
      infra- and supratentorial ROIs to account for differences in regional cerebral
      blood flow and volume. The presence of cerebellar hypoperfusion was calculated
      using an asymmetry index, with values of >10% being considered significant.
      RESULTS: We observed perfusion asymmetries in 23/106 patients, 22 in patients
      with migraine with aura (20.8%). Cerebellar hypoperfusion was observed in 12/23
      patients (52.2%), and crossed cerebellar diaschisis, in 9/23 patients (39.1%)
      with abnormal perfusion. In none of the 106 patients were DWI restrictions
      observed during migraine with aura. CONCLUSIONS: Cerebellar hypoperfusion and
      crossed cerebellar diaschisis are common in patients with migraine with aura and
      cortical perfusion abnormalities. Crossed cerebellar diaschisis in migraine with
      aura may be considered a benign phenomenon because we observed no association
      with DWI restriction or manifest cerebellar infarctions, even in patients with
      prolonged symptom-related perfusion abnormalities persisting for up to 24 hours.

PMID- 29326139
TI  - Carotid Artery Wall Imaging: Perspective and Guidelines from the ASNR Vessel Wall
      Imaging Study Group and Expert Consensus Recommendations of the American Society
      of Neuroradiology.
AB  - Identification of carotid artery atherosclerosis is conventionally based on
      measurements of luminal stenosis and surface irregularities using in vivo imaging
      techniques including sonography, CT and MR angiography, and digital subtraction
      angiography. However, histopathologic studies demonstrate considerable
      differences between plaques with identical degrees of stenosis and indicate that
      certain plaque features are associated with increased risk for ischemic events.
      The ability to look beyond the lumen using highly developed vessel wall imaging
      methods to identify plaque vulnerable to disruption has prompted an active debate
      as to whether a paradigm shift is needed to move away from relying on
      measurements of luminal stenosis for gauging the risk of ischemic injury. Further
      evaluation in randomized clinical trials will help to better define the exact
      role of plaque imaging in clinical decision-making. However, current carotid
      vessel wall imaging techniques can be informative. The goal of this article is to
      present the perspective of the ASNR Vessel Wall Imaging Study Group as it relates
      to the current status of arterial wall imaging in carotid artery disease.

PMID- 29326142
TI  - Gut Bacteria Shape Therapeutic Response.
AB  - The composition of patients' gut microbiomes influences whether they will respond
      to anti-PD-1 therapy, according to a trio of recently published studies. One of
      the studies also found that using antibiotics can reduce treatment efficacy,
      presumably by killing important species of gut bacteria. Now researchers are
      investigating how these findings can be used to increase the proportion of
      patients who respond to checkpoint inhibitor therapy.

PMID- 29326140
TI  - Navigating the residency application process for lesbian, gay, bisexual, and
      transgender student pharmacists.

PMID- 29326143
TI  - Seven days in medicine: 3-9 January 2018.

PMID- 29326144
TI  - A New Secretory Peptide of Natriuretic Peptide Family, Osteocrin, Suppresses the
      Progression of Congestive Heart Failure After Myocardial Infarction.
AB  - RATIONALE: An increase of severe ischemic heart diseases results in an increase
      of the patients with congestive heart failure (CHF). Therefore, new therapies are
      expected in addition to recanalization of coronary arteries. Previous clinical
      trials using natriuretic peptides (NPs) prove the improvement of CHF by NPs.
      OBJECTIVE: We aimed at investigating whether OSTN (osteocrin) peptide potentially
      functioning as an NPR (NP clearance receptor) 3-blocking peptide can be used as a
      new therapeutic peptide for treating CHF after myocardial infarction (MI) using
      animal models. METHODS AND RESULTS: We examined the effect of OSTN on circulation
      using 2 mouse models; the continuous intravenous infusion of OSTN after MI and
      the OSTN-transgenic (Tg) mice with MI. In vitro studies revealed that OSTN
      competitively bound to NPR3 with atrial NP. In both OSTN-continuous intravenous
      infusion model and OSTN-Tg model, acute inflammation within the first week after
      MI was reduced. Moreover, both models showed the improvement of prognosis at 28
      days after MI by OSTN. Consistent with the in vitro study binding of OSTN to
      NPR3, the OSTN-Tg exhibited an increased plasma atrial NP and C-type NP, which
      might result in the improvement of CHF after MI as indicated by the reduced
      weight of hearts and lungs and by the reduced fibrosis. CONCLUSIONS: OSTN might
      suppress the worsening of CHF after MI by inhibiting clearance of NP family
      peptides.

PMID- 29326145
TI  - Return to Work and Participation in Society After Out-of-Hospital Cardiac Arrest.
AB  - BACKGROUND: The aim of this study was to describe out-of-hospital cardiac arrest
      (OHCA) survivors' ability to participate in activities of everyday life and
      society, including return to work. The specific aim was to evaluate potential
      effects of cognitive impairment. METHODS AND RESULTS: Two hundred eighty-seven
      OHCA survivors included in the TTM trial (Target Temperature Management) and 119
      matched control patients with ST-segment-elevation myocardial infarction
      participated in a follow-up 180 days post-event that included assessments of
      participation, return to work, emotional problems, and cognitive impairment. On
      the Mayo-Portland Adaptability Inventory-4 Participation Index, OHCA survivors
      (n=270) reported more restricted participation In everyday life and in society
      (47% versus 30%; P<0.001) compared with ST-segment-elevation myocardial
      infarction controls (n=118). Furthermore, 27% (n=36) of pre-event working OHCA
      survivors (n=135) compared with 7% (n=3) of pre-event working ST-segment
      elevation myocardial infarction controls (n=45) were on sick leave (odds ratio,
      4.9; 95% confidence interval, 1.4-16.8; P=0.01). Among the OHCA survivors assumed
      to return to work (n=135), those with cognitive impairment (n=55) were 3* more
      likely (odds ratio, 3.3; 95% confidence interval, 1.2-9.3; P=0.02) to be on sick
      leave compared with those without cognitive impairment (n=40; 36%, n=20, versus
      15%, n=6). For OHCA survivors, the variables that were found most predictive for
      a lower participation were depression, restricted mobility, memory impairment,
      novel problem-solving difficulties, fatigue, and slower processing speed.
      CONCLUSIONS: OHCA survivors reported a more restricted societal participation 6
      months post-arrest, and their return to work was lower compared with ST-segment
      elevation myocardial infarction controls. Cognitive impairment was significantly
      associated with lower participation, together with the closely related symptoms
      of fatigue, depression, and restricted mobility. These predictive variables may
      be used during follow-up to identify OHCA survivors at risk of a less successful
      recovery that may benefit from further support and rehabilitation. CLINICAL TRIAL
      REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier:
      NCT01946932.

PMID- 29326146
TI  - Prior Authorization Requirements for Proprotein Convertase Subtilisin/Kexin Type
      9 Inhibitors Across US Private and Public Payers.
AB  - BACKGROUND: Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9is)
      are an innovative treatment option for patients with familial
      hypercholesterolemia or clinical atherosclerotic cardiovascular disease who
      require further lowering of low-density lipoprotein cholesterol. However, the
      high costs of these agents have spurred payers to implement utilization
      management policies to ensure appropriate use. We examined prior authorization
      (PA) requirements for PCSK9is across private and public US payers. METHODS AND
      RESULTS: We conducted an analysis of 2016 formulary coverage and PA data from a
      large, proprietary database with information on policies governing >95% of
      Americans with prescription drug coverage (275.3 million lives) within 3872 plans
      across the 4 major insurance segments (commercial, health insurance exchange,
      Medicare, and Medicaid). The key measures included administrative PA criteria
      (prescriber specialty, number of criteria in PA policy or number of fields on PA
      form, requirements for medical record submission, reauthorization requirements)
      and clinical/diagnostic PA criteria (approved conditions, required laboratories
      or other tests, required concomitant therapy, step therapy requirements,
      continuation criteria) for each of 2 Food and Drug Administration-approved
      PCSK9is. Select measures (eg, number of PA criteria/fields, medical record
      submission requirements) were obtained for 2 comparator cardiometabolic drugs
      (ezetimibe and liraglutide). Between 82% and 97% of individuals were enrolled in
      plans implementing PA for PCSK9is (depending on insurance segment), and one third
      to two thirds of these enrollees faced PAs restricting PCSK9i prescribing to a
      specialist. For patients with familial hypercholesterolemia, diagnostic
      confirmation via genetic testing or meeting minimum clinical scores/criteria was
      also required. PA requirements were more extensive for PCSK9is as compared with
      the other cardiometabolic drugs (ie, contained 3*-11* the number of PA criteria
      or fields on PA forms and more frequently involved the submission of medical
      records as supporting documentation). CONCLUSIONS: PA requirements for PCSK9is
      are greater than for selected other drugs within the cardiometabolic disease
      area, raising concerns about whether payer policies to discourage inappropriate
      use may also be restricting access to these drugs in patients who need them.

PMID- 29326147
TI  - Elephant in the Room: Cost of Proprotein Convertase Subtilisin/Kexin Type 9
      Inhibitors.

PMID- 29326148
TI  - Improving Neurological, Functional, and Participatory Survival After Cardiac
      Arrest.

PMID- 29326149
TI  - Correction.

PMID- 29326150
TI  - Diagnostic Performance of the Instantaneous Wave-Free Ratio: Comparison With
      Fractional Flow Reserve.
AB  - BACKGROUND: Aim of the present study was to perform a meta-analysis of all
      available studies comparing the instantaneous wave-free ratio (iFR) with
      fractional flow reserve (FFR). METHODS AND RESULTS: Published trials comparing
      the iFR with FFR were searched for in PubMed, Google Scholar, and Scopus
      electronic databases. A total of 23 studies were available for the analysis,
      including 6381 stenoses. First, a meta-analysis of all studies was performed
      exploring the correlation between FFR and iFR. Interestingly, we found good
      correlation (0.798 [0.78-0.82]) between the 2 indices (P<0.001). In addition, to
      evaluate the diagnostic performance of iFR to identify FFR-positive coronary
      stenoses, we performed an additional meta-analysis, summarizing the results of
      receiver operating characteristics analyses from individual studies reporting the
      area under the curve. Summing the results of these studies, we found that iFR has
      a good diagnostic performance for the identification of FFR-positive stenoses
      (area under the curve=0.88 [0.86-0.90]; P<0.001). Furthermore, our search results
      included 5 studies that compared iFR and FFR to a third independent reference
      standard. Interestingly, no significant differences between iFR and FFR were
      reported in those studies. CONCLUSIONS: The present meta-analysis shows that iFR
      significantly correlates with standard FFR and shows a good diagnostic
      performance in identifying FFR-positive coronary stenoses. Finally, iFR and FFR
      have similar diagnostic efficiency for detection of ischemia-inducing stenoses
      when tested against a third comparator.

PMID- 29326151
TI  - Sex-Based Assessment of Patient Presentation, Lesion Characteristics, and
      Treatment Modalities in Patients Undergoing Peripheral Vascular Intervention.
AB  - BACKGROUND: Limited evidence suggests that women and men might be treated
      differently for peripheral arterial disease. This analysis evaluated sex-based
      differences in disease presentation and its effect on treatment modality among
      patients who underwent endovascular treatment for peripheral arterial disease.
      METHODS AND RESULTS: Using national registry data from the Vascular Quality
      Initiative between 2010 and 2013, we examined patient, limb, and artery
      characteristics by sex through descriptive statistics. We studied 26 750
      procedures performed in 23 820 patients to treat 30 545 limbs and 44 804
      arteries. Women presented at an older age (69 versus 67 years; P<0.001) and were
      less often current or former smokers (72% versus 85%; P<0.001). Transatlantic
      Inter-Society Consensus classification was similar among men and women
      (Transatlantic Inter-Society Consensus C or D: 37% in men versus 37% in women;
      P=0.81), as was mean occlusion length (4.5 cm in men versus 4.6 cm in women;
      P=0.04), even after accounting for lesion location. Women more frequently
      underwent treatment for rest pain (11% in men versus 16% in women; P<0.001)
      versus claudication (59% in men versus 53% in women; P<0.001) or tissue loss (28%
      in men versus 27% in women; P=0.75). Treatment modality did not differ by sex but
      was associated with disease severity (P for trend <0.001) and lesion location (P
      for trend <0.001). CONCLUSIONS: Women undergo peripheral endovascular
      intervention for peripheral arterial disease at an older age with critical limb
      ischemia. Treatment modalities do not vary by sex but are determined by disease
      severity and site. Although there exist sex differences in presentation, these
      differences do not lead to differential treatment for women with peripheral
      arterial disease.

PMID- 29326152
TI  - Decision Analytic Markov Model Weighting Expected Benefits and Current
      Limitations of First-Generation Bioresorbable Vascular Scaffolds: Implications
      for Manufacturers and Next Device Iterations.
AB  - BACKGROUND: Relative benefits of bioresorbable vascular scaffolds (BVS) compared
      with everolimus-eluting stents (EES) are expected to accrue after complete
      bioresorption. METHODS AND RESULTS: We built a decision analytic Markov model
      comparing BVS and EES for a contemporary percutaneous coronary intervention
      population. Procedure-related morbidity and outcome data from the available
      literature were used to derive model probabilities. The net benefit of BVS and
      EES was estimated in terms of quality-adjusted life expectancy. Under the
      assumption of no risk for device thrombosis and target lesion revascularization
      with BVS beyond 3 years, the equipoise in quality-adjusted life expectancy
      (12.86) between BVS and EES was achieved 19 years after implantation. The maximum
      tolerable excess risk of 3-year BVS thrombosis equalizing the model-predicted
      quality-adjusted life expectancy of BVS and EES at 10 years was 1.40,
      corresponding to an absolute tolerable rate of 1.45%. CONCLUSIONS: At the
      currently observed relative increase in device thrombosis and under the extreme
      hypothesis of no scaffold thrombosis and target lesion revascularization beyond 3
      years, the incremental benefit of BVS over EES becomes apparent only after 19
      years. This simulation suggests that there is a small degree of benefit that
      clinicians and decision-makers may expect from the first-generation BVS at the
      current risk of device thrombosis. Manufacturers should target scaffold
      thrombosis rates <1.45% at 3 years to make their technologies attractive during a
      10-year horizon.

PMID- 29326154
TI  - What Happened to the Bioresorbable Scaffold Concept: Black Tide or Chernobyl?

PMID- 29326153
TI  - Treatment Effect of Drug-Coated Balloons Is Durable to 3 Years in the
      Femoropopliteal Arteries: Long-Term Results of the IN.PACT SFA Randomized Trial.
AB  - BACKGROUND: Randomized controlled trials have reported favorable 1-year outcomes
      with drug-coated balloons (DCBs) for the treatment of symptomatic peripheral
      arterial disease when compared with standard percutaneous transluminal
      angioplasty (PTA). Evidence remains limited on the durability of the treatment
      effect with DCBs in the longer term. METHODS AND RESULTS: IN.PACT SFA is a single
      blind, randomized trial (Randomized Trial of IN.PACT Admiral Paclitaxel-Coated
      Percutaneous Transluminal Angioplasty [PTA] Balloon Catheter vs Standard PTA for
      the Treatment of Atherosclerotic Lesions in the Superficial Femoral Artery [SFA]
      and/or Proximal Popliteal Artery [PPA]) that enrolled 331 patients with
      symptomatic (Rutherford 2-4) femoropopliteal lesions up to 18 cm in length.
      Patients were randomized 2:1 to receive treatment with DCB or PTA. The 36-month
      assessments included primary patency, freedom from clinically driven target
      lesion revascularization, major adverse events, and functional outcomes. At 36
      months, primary patency remained significantly higher among patients treated with
      DCB compared with PTA (69.5% versus 45.1%; log rank P<0.001). The rates of
      clinically driven target lesion revascularization were 15.2% and 31.1% (P=0.002)
      for the DCB and PTA groups, respectively. Functional outcomes were similarly
      improved between treatment groups even though subjects in the DCB group required
      significantly fewer reinterventions versus those in the PTA group (P<0.001 for
      target lesion revascularization, P=0.001 for target vessel revascularization).
      There were no device- or procedure-related deaths as adjudicated by an
      independent Clinical Events Committee. CONCLUSIONS: Three-year results
      demonstrate a durable and superior treatment effect among patients treated with
      DCB versus standard PTA, with significantly higher primary patency and lower
      clinically driven target lesion revascularization, resulting in similar
      functional improvements with reduced need for repeat interventions. CLINICAL
      TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifiers:
      NCT01175850 for IN.PACT SFA phase I in the European Union and NCT01566461 for
      IN.PACT SFA phase II in the United States.

PMID- 29326155
TI  - Instant Wave-Free Ratio or Fractional Flow Reserve for Hemodynamic Coronary
      Lesion Assessment? Yes, Just Do It!

PMID- 29326156
TI  - Leave No Stent Behind: Are Drug-Coated Balloons Enough for Femoropopliteal
      Disease?

PMID- 29326158
TI  - Reciprocal Spatiotemporally Controlled Apoptosis Regulates Wolffian Duct Cloaca
      Fusion.
AB  - The epithelial Wolffian duct (WD) inserts into the cloaca (primitive bladder)
      before metanephric kidney development, thereby establishing the initial plumbing
      for eventual joining of the ureters and bladder. Defects in this process cause
      common anomalies in the spectrum of congenital anomalies of the kidney and
      urinary tract (CAKUT). However, developmental, cellular, and molecular mechanisms
      of WD-cloaca fusion are poorly understood. Through systematic analysis of early
      WD tip development in mice, we discovered that a novel process of
      spatiotemporally regulated apoptosis in WD and cloaca was necessary for WD-cloaca
      fusion. Aberrant RET tyrosine kinase signaling through tyrosine (Y) 1062, to
      which PI3K- or ERK-activating proteins dock, or Y1015, to which PLCgamma docks,
      has been shown to cause CAKUT-like defects. Cloacal apoptosis did not occur in
      RetY1062F mutants, in which WDs did not reach the cloaca, or in RetY1015F
      mutants, in which WD tips reached the cloaca but did not fuse. Moreover,
      inhibition of ERK or apoptosis prevented WD-cloaca fusion in cultures, and WD
      specific genetic deletion of YAP attenuated cloacal apoptosis and WD-cloacal
      fusion in vivo Thus, cloacal apoptosis requires direct contact and signals from
      the WD tip and is necessary for WD-cloacal fusion. These findings may explain the
      mechanisms of many CAKUT.

PMID- 29326159
TI  - An intrinsic lipid-binding interface controls sphingosine kinase 1 function.
AB  - Sphingosine kinase 1 (SK1) is required for production of sphingosine-1-phosphate
      (S1P) and thereby regulates many cellular processes, including cellular growth,
      immune cell trafficking, and inflammation. To produce S1P, SK1 must access
      sphingosine directly from membranes. However, the molecular mechanisms underlying
      SK1's direct membrane interactions remain unclear. We used hydrogen/deuterium
      exchange MS to study interactions of SK1 with membrane vesicles. Using the
      CRISPR/Cas9 technique to generate HCT116 cells lacking SK1, we explored the
      effects of membrane interface disruption and the function of the SK1 interaction
      site. Disrupting the interface resulted in reduced membrane association and
      decreased cellular SK1 activity. Moreover, SK1-dependent signaling, including
      cell invasion and endocytosis, was abolished upon mutation of the membrane
      binding interface. Of note, we identified a positively charged motif on SK1 that
      is responsible for electrostatic interactions with membranes. Furthermore, we
      demonstrated that SK1 uses a single contiguous interface, consisting of an
      electrostatic site and a hydrophobic site, to interact with membrane-associated
      anionic phospholipids. Altogether, these results define a composite domain in SK1
      that regulates its intrinsic ability to bind membranes and indicate that this
      binding is critical for proper SK1 function. This work will allow for a new line
      of thinking for targeting SK1 in disease.

PMID- 29326160
TI  - Hypoxia-inducible lipid droplet-associated protein inhibits adipose triglyceride
      lipase.
AB  - Elaborate control mechanisms of intracellular triacylglycerol (TAG) breakdown are
      critically involved in the maintenance of energy homeostasis. Hypoxia-inducible
      lipid droplet-associated protein (HILPDA)/hypoxia-inducible gene-2 (Hig-2) has
      been shown to affect intracellular TAG levels, yet, the underlying molecular
      mechanisms are unclear. Here, we show that HILPDA inhibits adipose triglyceride
      lipase (ATGL), the enzyme catalyzing the first step of intracellular TAG
      hydrolysis. HILPDA shares structural similarity with G0/G1 switch gene 2 (G0S2),
      an established inhibitor of ATGL. HILPDA inhibits ATGL activity in a dose
      dependent manner with an IC50 value of ~2 MUM. ATGL inhibition depends on the
      direct physical interaction of both proteins and involves the N-terminal
      hydrophobic region of HILPDA and the N-terminal patatin domain-containing segment
      of ATGL. Finally, confocal microscopy combined with Forster resonance energy
      transfer-fluorescence lifetime imaging microscopy analysis indicated that HILPDA
      and ATGL colocalize and physically interact intracellularly. These findings
      provide a rational biochemical explanation for the tissue-specific increased TAG
      accumulation in HILPDA-overexpressing transgenic mouse models.

PMID- 29326157
TI  - Targeting B Cells and Plasma Cells in Glomerular Diseases: Translational
      Perspectives.
AB  - The unique contributions of memory B cells and plasma cells in kidney diseases
      remain unclear. In this review, we evaluate the clinical experience with
      treatments directed at B cells, such as rituximab, and at plasma cells, such as
      proteasome inhibition, to shed light on the role of these two B lineage
      compartments in glomerular diseases. Specifically, analysis of these targeted
      interventions in diseases such as ANCA-associated vasculitis, SLE, and antibody
      mediated transplant rejection permits insight into the pathogenetic effect of
      these cells. Notwithstanding the limitations of preclinical models and clinical
      studies (heterogeneous populations, among others), the data suggest that memory B
      and plasma cells represent two engines of autoimmunity, with variable involvement
      in these diseases. Whereas memory B cells and plasma cells appear to be key in
      ANCA-associated vasculitis and antibody-mediated transplant rejection,
      respectively, SLE seems likely to be driven by both autoimmune compartments.
      These conclusions have implications for the future development of targeted
      therapeutics in immune-mediated renal disease.

PMID- 29326162
TI  - Structural basis for (p)ppGpp synthesis by the Staphylococcus aureus small
      alarmone synthetase RelP.
AB  - The stringent response is a global reprogramming of bacterial physiology that
      renders cells more tolerant to antibiotics and induces virulence gene expression
      in pathogens in response to stress. This process is driven by accumulation of the
      intracellular alarmone guanosine-5'-di(tri)phosphate-3'-diphosphate ((p)ppGpp),
      which is produced by enzymes of the RelA SpoT homologue (RSH) family. The Gram
      positive Firmicute pathogen, Staphylococcus aureus, encodes three RSH enzymes: a
      multidomain RSH (Rel) that senses amino acid starvation on the ribosome and two
      small alarmone synthetase (SAS) enzymes, RelQ (SAS1) and RelP (SAS2). In Bacillus
      subtilis, RelQ (SAS1) was shown to form a tetramer that is activated by pppGpp
      and inhibited by single-stranded RNA, but the structural and functional
      regulation of RelP (SAS2) is unexplored. Here, we present crystal structures of
      S. aureus RelP in two major functional states, pre-catalytic (bound to GTP and
      the non-hydrolyzable ATP analogue, adenosine 5'-(alpha,beta
      methylene)triphosphate (AMP-CPP)), and post-catalytic (bound to pppGpp). We
      observed that RelP also forms a tetramer, but unlike RelQ (SAS1), it is strongly
      inhibited by both pppGpp and ppGpp and is insensitive to inhibition by RNA. We
      also identified putative metal ion-binding sites at the subunit interfaces that
      were consistent with the observed activation of the enzyme by Zn2+ ions. The
      structures reported here reveal the details of the catalytic mechanism of SAS
      enzymes and provide a molecular basis for understanding differential regulation
      of SAS enzymes in Firmicute bacteria.

PMID- 29326161
TI  - SUMO2/3 modification of activating transcription factor 5 (ATF5) controls its
      dynamic translocation at the centrosome.
AB  - Activating transcription factor 5 (ATF5) is a member of the ATF/cAMP response
      element-binding protein family of transcription factors. ATF5 regulates stress
      responses and cell survival, proliferation, and differentiation and also plays a
      role in viral infections, cancer, diabetes, schizophrenia, and the olfactory
      system. Moreover, it was found to also have a critical cell cycle-dependent
      structural function at the centrosome. However, the mechanism that controls the
      localization of ATF5 at the centrosome is unclear. Here we report that ATF5 is
      small ubiquitin-like modifier (SUMO) 2/3-modified at a conserved SUMO-targeting
      consensus site in various types of mammalian cells. We found that SUMOylation of
      ATF5 is elevated in the G1 phase of the cell cycle and diminished in the G2/M
      phase. ATF5 SUMOylation disrupted the interaction of ATF5 with several
      centrosomal proteins and dislodged ATF5 from the centrosome at the end of the M
      phase. Of note, blockade of ATF5 SUMOylation deregulated the centrosome cycle,
      impeded ATF5 translocation from the centrosome, and caused genomic instability
      and G2/M arrest in HeLa cells. Our results indicate that ATF5 SUMOylation is an
      essential mechanism that regulates ATF5 localization and function at the
      centrosome.

PMID- 29326163
TI  - LIM and cysteine-rich domains 1 is required for thrombin-induced smooth muscle
      cell proliferation and promotes atherogenesis.
AB  - Restenosis arises after vascular injury and is characterized by arterial wall
      thickening and decreased arterial lumen space. Vascular injury induces the
      production of thrombin, which in addition to its role in blood clotting acts as a
      mitogenic and chemotactic factor. In exploring the molecular mechanisms
      underlying restenosis, here we identified LMCD1 (LIM and cysteine-rich domains 1)
      as a gene highly responsive to thrombin in human aortic smooth muscle cells
      (HASMCs). Of note, LMCD1 depletion inhibited proliferation of human but not
      murine vascular smooth muscle cells. We also found that by physically interacting
      with E2F transcription factor 1, LMCD1 mediates thrombin-induced expression of
      the CDC6 (cell division cycle 6) gene in the stimulation of HASMC proliferation.
      Thrombin-induced LMCD1 and CDC6 expression exhibited a requirement for protease
      activated receptor 1-mediated Galphaq/11-dependent activation of phospholipase C
      beta3. Moreover, the expression of LMCD1 was highly induced in smooth muscle
      cells located at human atherosclerotic lesions and correlated with CDC6
      expression and that of the proliferation marker Ki67. Furthermore, the LMCD1- and
      SMCalphaactin-positive cells had higher cholesterol levels in the atherosclerotic
      lesions. In conclusion, these findings indicate that by acting as a co-activator
      with E2F transcription factor 1 in CDC6 expression, LMCD1 stimulates HASMC
      proliferation and thereby promotes human atherogenesis, suggesting an involvement
      of LMCD1 in restenosis.

PMID- 29326164
TI  - The glutamine transporter ASCT2 (SLC1A5) promotes tumor growth independently of
      the amino acid transporter LAT1 (SLC7A5).
AB  - The transporters for glutamine and essential amino acids, ASCT2 (solute carrier
      family 1 member 5, SLC1A5) and LAT1 (solute carrier family 7 member 5, SLC7A5),
      respectively, are overexpressed in aggressive cancers and have been identified as
      cancer-promoting targets. Moreover, previous work has suggested that glutamine
      influx via ASCT2 triggers essential amino acids entry via the LAT1 exchanger,
      thus activating mechanistic target of rapamycin complex 1 (mTORC1) and
      stimulating growth. Here, to further investigate whether these two transporters
      are functionally coupled, we compared the respective knockout (KO) of either LAT1
      or ASCT2 in colon (LS174T) and lung (A549) adenocarcinoma cell lines. Although
      ASCT2KO significantly reduced glutamine import (>60% reduction), no impact on
      leucine uptake was observed in both cell lines. Although an in vitro growth
      reduction phenotype was observed in A549-ASCT2KO cells only, we found that
      genetic disruption of ASCT2 strongly decreased tumor growth in both cell lines.
      However, in sharp contrast to LAT1KO cells, ASCT2KO cells displayed no amino acid
      (AA) stress response (GCN2/EIF2a/ATF4) or altered mTORC1 activity (S6K1/S6). We
      therefore conclude that ASCT2KO reduces tumor growth by limiting AA import, but
      that this effect is independent of LAT1 activity. These data were further
      supported by in vitro cell proliferation experiments performed in the absence of
      glutamine. Together these results confirm and extend ASCT2's pro-tumoral role and
      indicate that the proposed functional coupling model of ASCT2 and LAT1 is not
      universal across different cancer types.

PMID- 29326165
TI  - Phosphorylation-mediated structural changes within the SOAR domain of stromal
      interaction molecule 1 enable specific activation of distinct Orai channels.
AB  - Low-conductance, highly calcium-selective channels formed by the Orai proteins
      exist as store-operated CRAC channels and store-independent, arachidonic acid
      activated ARC channels. Both are activated by stromal interaction molecule 1
      (STIM1), but CRAC channels are activated by STIM1 located in the endoplasmic
      reticulum membrane, whereas ARC channels are activated by the minor plasma
      membrane-associated pool of STIM1. Critically, maximally activated CRAC channel
      and ARC channel currents are completely additive within the same cell, and their
      selective activation results in their ability to each induce distinct cellular
      responses. We have previously shown that specific ARC channel activation requires
      a PKA-mediated phosphorylation of a single threonine residue (Thr389) within the
      cytoplasmic region of STIM1. Here, examination of the molecular basis of this
      phosphorylation-dependent activation revealed that phosphorylation of the Thr389
      residue induces a significant structural change in the STIM1-Orai-activating
      region (SOAR) that interacts with the Orai proteins, and it is this change that
      determines the selective activation of the store-independent ARC channels versus
      the store-operated CRAC channels. In conclusion, our findings reveal the
      structural changes underlying the selective activation of STIM1-induced CRAC or
      ARC channels that determine the specific stimulation of these two functionally
      distinct Ca2+ entry pathways.

PMID- 29326166
TI  - A skeletal muscle L-type Ca2+ channel with a mutation in the selectivity filter
      (CaV1.1 E1014K) conducts K<sup/>.
AB  - A glutamate-to-lysine substitution at position 1014 within the selectivity filter
      of the skeletal muscle L-type Ca2+ channel (CaV1.1) abolishes Ca2+ flux through
      the channel pore. Mice engineered to exclusively express the mutant channel
      display accelerated muscle fatigue, changes in muscle composition, and altered
      metabolism relative to wildtype littermates. By contrast, mice expressing another
      mutant CaV1.1 channel that is impermeable to Ca2+ (CaV1.1 N617D) have shown no
      detectable phenotypic differences from wildtype mice to date. The major
      biophysical difference between the CaV1.1 E1014K and CaV1.1 N617D mutants
      elucidated thus far is that the former channel conducts robust Na+ and Cs+
      currents in patch-clamp experiments, but neither of these monovalent conductances
      seems to be of relevance in vivo Thus, the basis for the different phenotypes of
      these mutants has remained enigmatic. We now show that CaV1.1 E1014K readily
      conducts 1,4-dihydropyridine-sensitive K+ currents at depolarizing test
      potentials, whereas CaV1.1 N617D does not. Our observations, coupled with a large
      body of work by others regarding the role of K+ accumulation in muscle fatigue,
      raise the possibility that the introduction of an additional K+ flux from the
      myoplasm into the transverse-tubule lumen accelerates the onset of fatigue and
      precipitates the metabolic changes observed in CaV1.1 E1014K muscle. These
      results, highlighting an unexpected consequence of a channel mutation, may help
      define the complex mechanisms underlying skeletal muscle fatigue and related
      dysfunctions.

PMID- 29326167
TI  - The protein kinase CK2 substrate Jabba modulates lipid metabolism during
      Drosophila oogenesis.
AB  - Lipid metabolism plays a critical role in female reproduction. During oogenesis,
      maturing oocytes accumulate high levels of neutral lipids that are essential for
      both energy production and the synthesis of other lipid molecules. Metabolic
      pathways within the ovary are partially regulated by protein kinases that link
      metabolic status to oocyte development. Although the functions of several kinases
      in this process are well established, the roles that many other kinases play in
      coordinating metabolic state with female germ cell development are unknown. Here,
      we demonstrate that the catalytic activity of casein kinase 2 (CK2) is essential
      for Drosophila oogenesis. Using an unbiased biochemical screen that leveraged an
      unusual catalytic property of the kinase, we identified a novel CK2 substrate in
      the Drosophila ovary, the lipid droplet-associated protein Jabba. We show that
      Jabba is essential for modulating ovarian lipid metabolism and for regulating
      female fertility in the fly. Our findings shed light on a CK2-dependent signaling
      pathway governing lipid metabolism in the ovary and provide insight into the long
      recognized but poorly understood association between energy metabolism and female
      reproduction.

PMID- 29326170
TI  - Editorial.

PMID- 29326168
TI  - Cyclic di-adenosine monophosphate (c-di-AMP) is required for osmotic regulation
      in Staphylococcus aureus but dispensable for viability in anaerobic conditions.
AB  - Cyclic di-adenosine monophosphate (c-di-AMP) is a recently discovered signaling
      molecule important for the survival of Firmicutes, a large bacterial group that
      includes notable pathogens such as Staphylococcus aureus However, the exact role
      of this molecule has not been identified. dacA, the S. aureus gene encoding the
      diadenylate cyclase enzyme required for c-di-AMP production, cannot be deleted
      when bacterial cells are grown in rich medium, indicating that c-di-AMP is
      required for growth in this condition. Here, we report that an S. aureus dacA
      mutant can be generated in chemically defined medium. Consistent with previous
      findings, this mutant had a severe growth defect when cultured in rich medium.
      Using this growth defect in rich medium, we selected for suppressor strains with
      improved growth to identify c-di-AMP-requiring pathways. Mutations bypassing the
      essentiality of dacA were identified in alsT and opuD, encoding a predicted amino
      acid and osmolyte transporter, the latter of which we show here to be the main
      glycine betaine-uptake system in S. aureus. Inactivation of these transporters
      likely prevents the excessive osmolyte and amino acid accumulation in the cell,
      providing further evidence for a key role of c-di-AMP in osmotic regulation.
      Suppressor mutations were also obtained in hepS, hemB, ctaA, and qoxB, coding
      proteins required for respiration. Furthermore, we show that dacA is dispensable
      for growth in anaerobic conditions. Together, these findings reveal an essential
      role for the c-di-AMP signaling network in aerobic, but not anaerobic,
      respiration in S. aureus.

PMID- 29326169
TI  - Dual cyclooxygenase-fatty acid amide hydrolase inhibitor exploits novel binding
      interactions in the cyclooxygenase active site.
AB  - The cyclooxygenases COX-1 and COX-2 oxygenate arachidonic acid (AA) to
      prostaglandin H2 (PGH2). COX-2 also oxygenates the endocannabinoids 2
      arachidonoylglycerol (2-AG) and arachidonoylethanolamide (AEA) to the
      corresponding PGH2 analogs. Both enzymes are targets of nonsteroidal anti
      inflammatory drugs (NSAIDs), but NSAID-mediated COX inhibition is associated with
      gastrointestinal toxicity. One potential strategy to counter this toxicity is to
      also inhibit fatty acid amide hydrolase (FAAH), which hydrolyzes bioactive fatty
      acid ethanolamides (FAEs) into fatty acids and ethanolamine. Here, we
      investigated the mechanism of COX inhibition by ARN2508, an NSAID that inhibits
      both COXs and FAAH with high potency, target selectivity, and decreased
      gastrointestinal toxicity in mouse models, presumably due to its ability to
      increase levels of FAEs. A 2.27-A-resolution X-ray crystal structure of the COX
      2.(S)-ARN2508 complex reveals that ARN2508 adopts a binding pose similar to that
      of its parent NSAID flurbiprofen. However, ARN2508's alkyl tail is inserted deep
      into the top channel, an active site region not exploited by any previously
      reported NSAID. As for flurbiprofen, ARN2508's potency is highly dependent on the
      configuration of the alpha-methyl group. Thus, (S)-ARN2508 is more potent than
      (R)-ARN2508 for inhibition of AA oxygenation by both COXs and 2-AG oxygenation by
      COX-2. Also, similarly to (R)-flurbiprofen, (R)-ARN2508 exhibits substrate
      selectivity for inhibition of 2-AG oxygenation. Site-directed mutagenesis
      confirms the importance of insertion of the alkyl tail into the top channel for
      (S)-ARN2508's potency and suggests a role for Ser-530 as a determinant of the
      inhibitor's slow rate of inhibition compared with that of (S)-flurbiprofen.

PMID- 29326171
TI  - Abdominal Vagal Afferents Modulate the Brain Transcriptome and Behaviors Relevant
      to Schizophrenia.
AB  - Reduced activity of vagal efferents has long been implicated in schizophrenia and
      appears to be responsible for diminished parasympathetic activity and associated
      peripheral symptoms such as low heart rate variability and cardiovascular
      complications in affected individuals. In contrast, only little attention has
      been paid to the possibility that impaired afferent vagal signaling may be
      relevant for the disorder's pathophysiology as well. The present study explored
      this hypothesis using a model of subdiaphragmatic vagal deafferentation (SDA) in
      male rats. SDA represents the most complete and selective vagal deafferentation
      method existing to date as it leads to complete disconnection of all abdominal
      vagal afferents while sparing half of the abdominal vagal efferents. Using next
      generation mRNA sequencing, we show that SDA leads to brain transcriptional
      changes in functional networks annotating with schizophrenia. We further
      demonstrate that SDA induces a hyperdopaminergic state, which manifests itself as
      increased sensitivity to acute amphetamine treatment and elevated accumbal levels
      of dopamine and its major metabolite, 3,4-dihydroxyphenylacetic acid. Our study
      also shows that SDA impairs sensorimotor gating and the attentional control of
      associative learning, which were assessed using the paradigms of prepulse
      inhibition and latent inhibition, respectively. These data provide converging
      evidence suggesting that the brain transcriptome, dopamine neurochemistry, and
      behavioral functions implicated in schizophrenia are subject to visceral
      modulation through abdominal vagal afferents. Our findings may encourage the
      further establishment and use of therapies for schizophrenia that are based on
      vagal interventions.SIGNIFICANCE STATEMENT The present work provides a better
      understanding of how disrupted vagal afferent signaling can contribute to
      schizophrenia-related brain and behavioral abnormalities. More specifically, it
      shows that subdiaphragmatic vagal deafferentation (SDA) in rats leads to (1)
      brain transcriptional changes in functional networks related to schizophrenia,
      (2) increased sensitivity to dopamine-stimulating drugs and elevated dopamine
      levels in the nucleus accumbens, and (3) impairments in sensorimotor gating and
      the attentional control of associative learning. These findings may encourage the
      further establishment of novel therapies for schizophrenia that are based on
      vagal interventions.

PMID- 29326172
TI  - Diversity and Connectivity of Layer 5 Somatostatin-Expressing Interneurons in the
      Mouse Barrel Cortex.
AB  - Inhibitory interneurons represent 10-15% of the neurons in the somatosensory
      cortex, and their activity powerfully shapes sensory processing. Three major
      groups of GABAergic interneurons have been defined according to developmental,
      molecular, morphological, electrophysiological, and synaptic features. Dendritic
      targeting somatostatin-expressing interneurons (SST-INs) have been shown to
      display diverse morphological, electrophysiological, and molecular properties and
      activity patterns in vivo However, the correlation between these properties and
      SST-IN subtype is unclear. In this study, we aimed to correlate the morphological
      diversity of layer 5 (L5) SST-INs with their electrophysiological and molecular
      diversity in mice of either sex. Our morphological analysis demonstrated the
      existence of three subtypes of L5 SST-INs with distinct electrophysiological
      properties: T-shaped Martinotti cells innervate L1, and are low-threshold
      spiking; fanning-out Martinotti cells innervate L2/3 and the lower half of L1,
      and show adapting firing patterns; non-Martinotti cells innervate L4, and show a
      quasi-fast spiking firing pattern. We estimated the proportion of each subtype in
      L5 and found that T-shaped Martinotti, fanning-out Martinotti, and Non-Martinotti
      cells represent ~10, ~50, and ~40% of L5 SST-INs, respectively. Last, we examined
      the connectivity between the three SST-IN subtypes and L5 pyramidal cells (PCs).
      We found that L5 T-shaped Martinotti cells inhibit the L1 apical tuft of nearby
      PCs; L5 fanning-out Martinotti cells also inhibit nearby PCs but they target the
      dendrite mainly in L2/3. On the other hand, non-Martinotti cells inhibit the
      dendrites of L4 neurons while avoiding L5 PCs. Our data suggest that
      morphologically distinct SST-INs gate different excitatory inputs in the barrel
      cortex.SIGNIFICANCE STATEMENT Morphologically diverse layer 5 SST-INs show
      different patterns of activity in behaving animals. However, little is known
      about the abundance and connectivity of each morphological type and the
      correlation between morphological subtype and spiking properties. We demonstrate
      a correlation between the morphological and electrophysiological diversity of
      layer 5 SST-INs. Based on these findings we built a classifier to infer the
      abundance of each morphological subtype. Last, using paired recordings combined
      with morphological analysis, we investigated the connectivity of each
      morphological subtype. Our data suggest that, by targeting different cell types
      and cellular compartments, morphologically diverse SST-INs might gate different
      excitatory inputs in the mouse barrel cortex.

PMID- 29326173
TI  - Transcriptional Regulator ZEB2 Is Essential for Bergmann Glia Development.
AB  - Bergmann glia facilitate granule neuron migration during development and maintain
      the cerebellar organization and functional integrity. At present, molecular
      control of Bergmann glia specification from cerebellar radial glia is not fully
      understood. In this report, we show that ZEB2 (aka, SIP1 or ZFHX1B), a Mowat
      Wilson syndrome-associated transcriptional regulator, is highly expressed in
      Bergmann glia, but hardly detectable in astrocytes in the cerebellum. The mice
      lacking Zeb2 in cerebellar radial glia exhibit severe deficits in Bergmann glia
      specification, and develop cerebellar cortical lamination dysgenesis and
      locomotion defects. In developing Zeb2-mutant cerebella, inward migration of
      granule neuron progenitors is compromised, the proliferation of glial precursors
      is reduced, and radial glia fail to differentiate into Bergmann glia in the
      Purkinje cell layer. In contrast, Zeb2 ablation in granule neuron precursors or
      oligodendrocyte progenitors does not affect Bergmann glia formation, despite
      myelination deficits caused by Zeb2 mutation in the oligodendrocyte lineage.
      Transcriptome profiling identified that ZEB2 regulates a set of Bergmann glia
      related genes and FGF, NOTCH, and TGFbeta/BMP signaling pathway components. Our
      data reveal that ZEB2 acts as an integral regulator of Bergmann glia formation
      ensuring maintenance of cerebellar integrity, suggesting that ZEB2 dysfunction in
      Bergmann gliogenesis might contribute to motor deficits in Mowat-Wilson
      syndrome.SIGNIFICANCE STATEMENT Bergmann glia are essential for proper cerebellar
      organization and functional circuitry, however, the molecular mechanisms that
      control the specification of Bergmann glia remain elusive. Here, we show that
      transcriptional factor ZEB2 is highly expressed in mature Bergmann glia, but not
      in cerebellar astrocytes. The mice lacking Zeb2 in cerebellar radial glia, but
      not oligodendrocyte progenitors or granular neuron progenitors, exhibit severe
      defects in Bergmann glia formation. The orderly radial scaffolding formed by
      Bergmann glial fibers critical for cerebellar lamination was not established in
      Zeb2 mutants, displaying motor behavior deficits. This finding demonstrates a
      previously unrecognized critical role for ZEB2 in Bergmann glia specification,
      and points to an important contribution of ZEB2 dysfunction to cerebellar motor
      disorders in Mowat-Wilson syndrome.

PMID- 29326175
TI  - Birth options after a caesarean section.

PMID- 29326174
TI  - Muscle Nicotinic Acetylcholine Receptors May Mediate Trans-Synaptic Signaling at
      the Mouse Neuromuscular Junction.
AB  - Block of neurotransmitter receptors at the neuromuscular junction (NMJ) has been
      shown to trigger upregulation of the number of synaptic vesicles released
      (quantal content, QC), a response termed homeostatic synaptic plasticity. The
      mechanism underlying this plasticity is not known. Here, we used selective toxins
      to demonstrate that block of alpha1-containing nicotinic acetylcholine receptors
      (nAChRs) at the NMJ of male and female mice triggers the upregulation of QC.
      Reduction of current flow through nAChRs, induced by drugs with antagonist
      activity, demonstrated that reduction in synaptic current per se does not trigger
      upregulation of QC. These data led to the remarkable conclusion that disruption
      of synaptic transmission is not sensed to trigger upregulation of QC. During
      studies of the effect of partial block of nAChRs on QC, we observed a small but
      reproducible increase in the decay kinetics of miniature synaptic currents. The
      change in kinetics was correlated with the increase in QC and raises the
      possibility that a change in postsynaptic nAChR conformation may be associated
      with the presynaptic increase in QC. We propose that, in addition to functioning
      in synaptic transmission, ionotropic muscle nicotonic nAChRs may serve as
      signaling molecules that participate in synaptic plasticity. Because nAChRs have
      been implicated in a number of disease states, the finding that nAChRs may be
      involved in triggering synaptic plasticity could have wide-reaching
      implications.SIGNIFICANCE STATEMENT The signals that initiate synaptic plasticity
      of the nervous system are still incompletely understood. Using the mouse
      neuromuscular junction as a model synapse, we studied how block of
      neurotransmitter receptors is sensed to trigger synaptic plasticity. Our studies
      led to the surprising conclusion that neither changes in synaptic current nor
      spiking of the presynaptic or postsynaptic cell are sensed to initiate synaptic
      plasticity. Instead, postsynaptic nicotinic acetylcholine receptors (nAChRs), in
      addition to functioning in synaptic transmission, may serve as signaling
      molecules that trigger synaptic plasticity. Because nAChRs have been implicated
      in a number of disease states, the finding that they may mediate synaptic
      plasticity has broad implications.

PMID- 29326177
TI  - STIs in sex partners notified for chlamydia exposure: implications for expedited
      partner therapy.
AB  - OBJECTIVES: Expedited partner therapy (EPT) may reduce chlamydia reinfection
      rates. However, the disadvantages of EPT for chlamydia include missing the
      opportunity to test for other STIs and unnecessary use of antibiotics among non
      infected partners. As part of a larger study that investigated the feasibility of
      EPT in the Netherlands, we explored the frequency of STI among a potential EPT
      target population of chlamydia-notified heterosexual men and women attending STI
      clinics for testing. METHODS: Cross-sectional national STI/HIV surveillance data,
      which contain information on all consultations at STI clinics, were used to
      calculate STI positivity rates stratified by chlamydia notification and gender,
      and proportions of STI that were attributable to clients notified for chlamydia.
      RESULTS: Of all consultations in 2015 (n=101 710), 14 445 (14.4%) clients
      reported to be notified exclusively for chlamydia. Among chlamydia-notified
      clients, the chlamydia positivity rate was 34.2% (n=4947), and consequently 65.8%
      (n=9488) of them tested negative for chlamydia. Chlamydia-notified clients
      contributed to 10.2% of all gonorrhoea infections (n=174/1702) and 10.9% of all
      infectious syphilis, HIV and/or infectious hepatitis B infections (n=15/173).
      CONCLUSION: Implementing EPT without additional STI testing for all partners of
      chlamydia-infected index patients implies that STIs other than chlamydia will be
      missed. Although the chlamydia positivity rate was high among chlamydia-notified
      partners, two-thirds would unnecessarily use azithromycin. An evaluation of EPT
      against the current partner treatment strategy is needed to carefully weigh the
      potential health gains against the potential health losses and to explore the
      characteristics of EPT-eligible partners.

PMID- 29326176
TI  - Combinatorial Omics Analysis Reveals Perturbed Lysosomal Homeostasis in Collagen
      VII-deficient Keratinocytes.
AB  - The extracellular matrix protein collagen VII is part of the microenvironment of
      stratified epithelia and critical in organismal homeostasis. Mutations in the
      encoding gene COL7A1 lead to the skin disorder dystrophic epidermolysis bullosa
      (DEB), are linked to skin fragility and progressive inflammation-driven fibrosis
      that facilitates aggressive skin cancer. So far, these changes have been linked
      to mesenchymal alterations, the epithelial consequences of collagen VII loss
      remaining under-addressed. As epithelial dysfunction is a principal initiator of
      fibrosis, we performed a comprehensive transcriptome and proteome profiling of
      primary human keratinocytes from DEB and control subjects to generate global and
      detailed images of dysregulated epidermal molecular pathways linked to loss of
      collagen VII. These revealed downregulation of interaction partners of collagen
      VII on mRNA and protein level, but also increased abundance of S100 pro
      inflammatory proteins in primary DEB keratinocytes. Increased TGF-beta signaling
      because of loss of collagen VII was associated with enhanced activity of
      lysosomal proteases in both keratinocytes and skin of collagen VII-deficient
      individuals. Thus, loss of a single structural protein, collagen VII, has extra-
      and intracellular consequences, resulting in inflammatory processes that enable
      tissue destabilization and promote keratinocyte-driven, progressive fibrosis.

PMID- 29326178
TI  - Impact of replacing cytology with human papillomavirus testing for cervical
      cancer screening on the prevalence of Trichomonas vaginalis: a modelling study.
AB  - OBJECTIVES: Trichomonas vaginalis (TV) is the most common curable STI worldwide
      and is associated with increased risk of HIV acquisition and serious reproductive
      morbidities. The prevalence of TV infection is very low in Australian cities, and
      this is thought to be at least partly due to incidental detection and treatment
      of TV in women participating in the cervical cytology screening programme. In
      2017, the national cervical screening programme will transition to a new model
      based on testing for high-risk (HR) human papillomavirus (HPV), with a reduced
      frequency and commencement at an older age. We model the potential impact of this
      transition on TV prevalence in Australia. METHODS: A mathematical model was
      developed to describe the transmission of TV in the general population and used
      to evaluate scenarios that capture the switch from cytology-based screening to HR
      HPV testing. Under these scenarios, individuals with asymptomatic TV who test
      negative for HR HPV will remain undiagnosed and untreated. We estimate the change
      in TV prevalence expected to occur due to the switch from cytology to HR HPV
      testing and changes to the frequency and age at commencement of screening.
      RESULTS: Our results suggest that with the transition to HR HPV testing, TV
      prevalence may increase from the current ~0.4% to 2.8% within 20 years if TV
      testing coverage is not increased and HR HPV prevalence does not decline further.
      If HR HPV prevalence continues to decline at its current rate with ongoing
      vaccination, TV prevalence is predicted to increase to 3.0% within this time
      frame. CONCLUSIONS: Our modelling suggests that in a setting like Australia,
      where TV can be detected incidentally through cytology-based cervical screening,
      a transition to HPV testing is likely to result in increasing TV prevalence over
      time unless additional measures are implemented to increase TV testing and
      treatment.

PMID- 29326179
TI  - Mixed-methods evaluation of a novel online STI results service.
AB  - OBJECTIVES: Evidence on optimal methods for providing STI test results is
      lacking. We evaluated an online results service, developed as part of an eSexual
      Health Clinic (eSHC). METHODS: We evaluated the online results service using a
      mixed-methods approach within large exploratory studies of the eSHC. Participants
      were chlamydia- positive and negative users of online postal self-sampling
      services in six National Chlamydia Screening Programme (NCSP) areas and chlamydia
      positive patients from two genitourinary medicine (GUM) clinics between 21 July
      2014 and 13 March 2015. Participants received a discreetly worded National Health
      Service 'NHS no-reply' text message (SMS) informing them that their test results
      were ready and providing a weblink to a secure website. Participants logged in
      with their date of birth and mobile telephone or clinic number. Chlamydia
      positive patients were offered online management. All interactions with the eSHC
      system were automatically logged and their timing recorded. Post-treatment, a
      service evaluation survey (n=152) and qualitative interviews (n=36) were
      conducted by telephone. Chlamydia-negative patients were offered a short online
      survey (n=274). Data were integrated. RESULTS: 92% (134/146) of NCSP chlamydia
      positive patients, 82% (161/197) of GUM chlamydia-positive patients and 89%
      (1776/1997) of NCSP chlamydia-negative participants accessed test results within
      7 days. 91% of chlamydia-positive patients were happy with the results service;
      64% of those who had tested previously found the results service better or much
      better than previous experiences. 90% of chlamydia-negative survey participants
      agreed they would be happy to receive results this way in the future.
      Interviewees described accessing results with ease and appreciated the privacy
      and control the two-step process gave them. CONCLUSION: A discreet SMS to alert
      users/patients that results are available, followed by provision of results via a
      secure website, was highly acceptable, irrespective of test result and testing
      history. The eSHC results service afforded users privacy and control over when
      they viewed results without compromising access.

PMID- 29326181
TI  - What are the sources of stress and distress for general practitioners working in
      England? A qualitative study.
AB  - OBJECTIVES: This paper reports the sources of stress and distress experienced by
      general practitioners (GP) as part of a wider study exploring the barriers and
      facilitators to help-seeking for mental illness and burnout among this medical
      population. DESIGN: Qualitative study using in-depth interviews with 47 GP
      participants. The interviews were audio-recorded, transcribed, anonymised and
      imported into NVivo V.11 to facilitate data management. Data were analysed using
      a thematic analysis employing the constant comparative method. SETTING: England.
      PARTICIPANTS: A purposive sample of GP participants who self-identified as: (1)
      currently living with mental distress, (2) returning to work following treatment,
      (3) off sick or retired early as a result of mental distress or (4) without
      experience of mental distress. Interviews were conducted face-to-face or over the
      telephone. RESULTS: The key sources of stress/distress related to: (1) emotion
      work-the work invested and required in managing and responding to the
      psychosocial component of GPs' work, and dealing with abusive or confrontational
      patients; (2) practice culture-practice dynamics and collegial conflict,
      bullying, isolation and lack of support; (3) work role and demands-fear of making
      mistakes, complaints and inquests, revalidation, appraisal, inspections and
      financial worries. CONCLUSION: In addition to addressing escalating workloads
      through the provision of increased resources, addressing unhealthy practice
      cultures is paramount. Collegial support, a willingness to talk about
      vulnerability and illness, and having open channels of communication enable GPs
      to feel less isolated and better able to cope with the emotional and clinical
      demands of their work. Doctors, including GPs, are not invulnerable to the
      clinical and emotional demands of their work nor the effects of divisive work
      cultures-culture change and access to informal and formal support is therefore
      crucial in enabling GPs to do their job effectively and to stay well.

PMID- 29326180
TI  - Prevalence and burden of chronic kidney disease among the general population and
      high-risk groups in Africa: a systematic review.
AB  - OBJECTIVES: While increasing attention is paid to the rising prevalence of
      chronic diseases in Africa, there is little focus on chronic kidney disease
      (CKD). This systematic review assesses CKD burden among the general population
      and high-risk groups on the entire African continent. DESIGN, SETTING AND
      PARTICIPANTS: We searched Medline and PubMed databases for articles published
      between 1 January 1995 and 7 April 2017 by sensitive search strategies focusing
      on CKD surveys at the community level and high-risk groups. In total, 7918
      references were evaluated, of which 7766 articles were excluded because they did
      not meet the inclusion criteria. Thus, 152 studies were included in the final
      analysis. OUTCOME MEASUREMENT: The prevalence of CKD in each study group was
      expressed as a range and pooled prevalence rate of CKD was calculated as a point
      estimate and 95% CI. No meta-analysis was done. Data were presented for different
      populations. RESULTS: In the community-level studies, based on available medium
      quality and high-quality studies, the prevalence of CKD ranged from 2% to 41%
      (pooled prevalence: 10.1%; 95% CI 9.8% to 10.5%). The prevalence of CKD in the
      high-risk groups ranged from 1% to 46% (pooled prevalence: 5.6%; 95% CI 5.4% to
      5.8%) in patients with HIV (based on available medium-quality and high-quality
      studies), 11%-90% (pooled prevalence: 24.7%; 95% CI 23.6% to 25.7%) in patients
      with diabetes (based on all available studies which are of low quality except
      four of medium quality) and 13%-51% (pooled prevalence: 34.5%; 95 % CI 34.04% to
      36%) in patients with hypertension (based on all available studies which are of
      low quality except two of medium quality). CONCLUSION: In Africa, CKD is a public
      health problem, mainly attributed to high-risk conditions as hypertension and
      diabetes. The poor data quality restricts the validity of the findings and draws
      the attention to the importance of designing future robust studies.

PMID- 29326183
TI  - Transvaginal natural orifice transluminal endoscopic surgery (vNOTES) adnexectomy
      for benign pathology compared with laparoscopic excision (NOTABLE): a protocol
      for a randomised controlled trial.
AB  - INTRODUCTION: Natural orifice transluminal endoscopic surgery (NOTES) uses
      natural orifices to access the cavities of the human body to perform surgical
      interventions. NOTES limits the magnitude of surgical trauma and potentially
      reduces postoperative pain. Our group published a protocol on a randomised study
      comparing transvaginal NOTES (vNOTES) versus laparoscopy for hysterectomy
      (HALON). We simultaneously designed a similar randomised controlled trial (RCT)
      comparing vNOTES with laparoscopy for adnexectomy. To the best of our knowledge,
      this is the first RCT comparing vNOTES with laparoscopy for adnexal surgery.
      METHODS AND ANALYSIS: The methodology of the Notes Adnexectomy for Benign
      Indication versus Laparoscopic Excision (NOTABLE) study is similar to that of the
      HALON trial. Women aged 18-70 years with an indication for benign adnexal surgery
      will be eligible. We will use stratification according to adnexal size. Entrants
      will be randomised to the laparoscopic treatment (control) or vNOTES
      (intervention). Participants will be evaluated on days 0-7 and at 3 and 6 months.
      The primary outcome will be the proportion of women successfully treated by
      removing an adnexa by the allocated technique without conversion. We will collect
      the following data (secondary outcomes): proportion of women hospitalised on the
      day of surgery, postoperative pain scores measured two times per day from day 1
      to 7, total dosage of pain killers used from day 1 to 7, hospital readmission
      during the first 6 weeks, dyspareunia and sexual well-being at baseline, 3 and 6
      months using a validated questionnaire (Short Sexual Functioning Scale), health
      related quality of life at baseline, 3 and 6 months after surgery using a
      validated questionnaire (EQ-5D-3L), duration of surgical intervention, infection
      or other surgical complications and direct costs up to 6 weeks following surgery.
      For the primary outcome measure, a one-sided 95% CI of the difference in the
      proportions of women with a successful removal of the uterus by the randomised
      technique will be estimated. Non-inferiority will be concluded when 15% lies
      above the upper limit of this 95% CI. ETHICS AND DISSEMINATION: The study was
      approved on 1 December 2015 by the EthicsCommitteeof the Imelda Hospital
      (registration no: 689), Bonheiden, Belgium. We aim to present the final results
      of the NOTABLE trial in peer-reviewed journals and at scientific meetings within
      4 years after the start of the recruitment. TRIAL REGISTRATION NUMBER:
      NCT02630329.

PMID- 29326182
TI  - Variations in childbirth interventions in high-income countries: protocol for a
      multinational cross-sectional study.
AB  - INTRODUCTION: There are growing concerns about the increase in rates of commonly
      used childbirth interventions. When indicated, childbirth interventions are
      crucial for preventing maternal and perinatal morbidity and mortality, but their
      routine use in healthy women and children leads to avoidable maternal and
      neonatal harm. Establishing ideal rates of interventions can be challenging. This
      study aims to describe the range of variations in the use of commonly used
      childbirth interventions in high-income countries around the world, and in
      outcomes in nulliparous and multiparous women. METHODS AND ANALYSIS: This
      multinational cross-sectional study will use data from births in 2013 with
      national population data or representative samples of the population of pregnant
      women in high-income countries. Data from women who gave birth to a single child
      from 37 weeks gestation onwards will be included and the results will be
      presented for nulliparous and multiparous women separately. Anonymised individual
      level data will be analysed. Primary outcomes are rates of commonly used
      childbirth interventions, including induction and/or augmentation of labour,
      intrapartum antibiotics, epidural and pharmacological pain relief, episiotomy in
      vaginal births, instrument-assisted birth (vacuum or forceps), caesarean section
      and use of oxytocin postpartum. Secondary outcomes are maternal and perinatal
      mortality, Apgar score below 7 at 5 min, postpartum haemorrhage and obstetric
      anal sphincter injury. Univariable and multivariable logistic regression analyses
      will be conducted to investigate variations among countries, adjusted for
      maternal age, body mass index, gestational weight gain, ethnic background,
      socioeconomic status and infant birth weight. The overall mean rates will be
      considered as a reference category, weighted for the size of the study population
      per country. ETHICS AND DISSEMINATION: The Medical Ethics Review Committee of VU
      University Medical Center Amsterdam confirmed that an official approval of this
      study was not required. Results will be disseminated at national and
      international conferences and published in peer-reviewed journals.

PMID- 29326184
TI  - Assessing the effectiveness of a patient-centred computer-based clinic
      intervention, Health-E You/Salud iTu, to reduce health disparities in unintended
      pregnancies among Hispanic adolescents: study protocol for a cluster randomised
      control trial.
AB  - INTRODUCTION: Teen pregnancy rates in the USA remain higher than any other
      industrialised nation, and pregnancies among Hispanic adolescents are
      disproportionately high. Computer-based interventions represent a promising
      approach to address sexual health and contraceptive use disparities. Preliminary
      findings have demonstrated that the Health-E You/Salud iTu, computer application
      (app) is feasible to implement, acceptable to Latina adolescents and improves
      sexual health knowledge and interest in selecting an effective contraceptive
      method when used in conjunction with a healthcare visit. The app is now ready for
      efficacy testing. The purpose of this manuscript is to describe patient-centred
      approaches used both in developing and testing the Health-E You app and to
      present the research methods used to evaluate its effectiveness in improving
      intentions to use an effective method of contraception as well as actual
      contraceptive use. METHODS AND ANALYSIS: This study is designed to assess the
      effectiveness of a patient-centred computer-based clinic intervention, Health-E
      You/Salud iTu, on its ability to reduce health disparities in unintended
      pregnancies among Latina adolescent girls. This study uses a cluster randomised
      control trial design in which 18 school-based health centers from the Los Angeles
      Unified School District were randomly assigned, at equal chance, to either the
      intervention (Health-E You app) or control group. Analyses will examine
      differences between the control and intervention group's knowledge of and
      attitudes towards contraceptive use, receipt of contraception at the clinic visit
      and self-reported use of contraception at 3-month and 6-month follow-ups. The
      study began enrolling participants in August 2016, and a total of 1400
      participants (700 per treatment group) are expected to be enrolled by March 2018.
      ETHICS AND DISSEMINATION: Ethics approval was obtained through the University of
      California, San Francisco Institutional Review Board. Results of this trial will
      be submitted for publication in peer-reviewed journals. This study is registered
      with the US National Institutes of Health. TRIAL REGISTRATION NUMBER:
      NCT02847858.

PMID- 29326186
TI  - Factors associated with neonatal pneumonia in India: protocol for a systematic
      review and planned meta-analysis.
AB  - INTRODUCTION: India accounts for more neonatal deaths than any other country.
      There is a lack of consolidated evidence from India regarding the determining
      factors of pneumonia in neonates. This systematic review is aimed to consolidate
      and appraise the evidence on risk factors and determinants of pneumonia among
      neonates in India. METHODS AND ANALYSIS: This protocol is part of a project
      consisting of three reviews (two systematic reviews and one scoping review) and a
      qualitative study on neonatal pneumonia in India. English language observational
      studies which report risk factors and determinants of neonatal pneumonia in India
      will be eligible for inclusion. Electronic searching of nine databases, and hand
      searching will be done. Two authors will independently conduct screening (title,
      abstract and full-text stages), extract data and assess risk of bias. A meta
      analysis is planned to be performed with random-effects model. A narrative
      synthesis will be used to summarise the characteristics and findings of the
      review, if a meta-analysis cannot be performed. If there are more than 10
      studies, publication bias will be assessed. Sensitivity and subgroup analysis
      will performed based on data availability. The quality of our review will be
      assessed by using 'Assessing the Methodological quality of Systematic Reviews'
      and 'Grades of Recommendation, Assessment, Development and Evaluation'. ETHICS
      AND DISSEMINATION: The protocol of the entire project has been approved by the
      host institution's ethics body (Institutional Ethics Committee, Manipal
      University, Manipal, India), and the 'Health Ministry Screening Committee' under
      the Ministry of Health and Family Welfare, Government of India. The study
      findings will be disseminated among relevant stakeholders using knowledge
      dissemination workshops, policy briefs, publications, etc. PROSPERO REGISTRATION
      NUMBER: CRD42016044019.

PMID- 29326185
TI  - Enhancing prescribing of guideline-recommended medications for ischaemic heart
      diseases: a systematic review and meta-analysis of interventions targeted at
      healthcare professionals.
AB  - OBJECTIVES: Ischaemic heart diseases (IHDs) are a leading cause of death
      worldwide. Although prescribing according to guidelines improves health outcomes,
      it remains suboptimal. We determined whether interventions targeted at healthcare
      professionals are effective to enhance prescribing and health outcomes in
      patients with IHDs. METHODS: We systematically searched PubMed and EMBASE for
      studies published between 1 January 2000 and 31 August 2017. We included original
      studies of interventions targeted at healthcare professionals to enhance
      prescribing guideline-recommended medications for IHDs. We only included
      randomised controlled trials (RCTs). Main outcomes were the proportion of
      eligible patients receiving guideline-recommended medications, the proportion of
      patients achieving target blood pressure and target low-density lipoprotein
      cholesterol (LDL-C)/cholesterol level and mortality rate. Meta-analyses were
      performed using the inverse-variance method and the random effects model. The
      quality of evidence was assessed using the Grading of Recommendations,
      Assessment, Development, and Evaluation approach. RESULTS: We included 13
      studies, 4 RCTs (1869 patients) and 9 cluster RCTs (15 224 patients). 11 out of
      13 studies were performed in North America and Europe. Interventions were of
      organisational or professional nature. The interventions significantly enhanced
      prescribing of statins/lipid-lowering agents (OR 1.23; 95% CI 1.07 to 1.42,
      P=0.004), but not other medications (aspirin/antiplatelet agents, beta-blockers,
      ACE inhibitors/angiotensin II receptor blockers and the composite of
      medications). There was no significant association between the interventions and
      improved health outcomes (target LDL-C and mortality) except for target blood
      pressure (OR 1.46; 95% CI 1.11 to 1.93; P=0.008). The evidence was of moderate or
      high quality for all outcomes. CONCLUSIONS: Organisational and professional
      interventions improved prescribing of statins/lipid-lowering agents and target
      blood pressure in patients with IHDs but there was little evidence of change in
      other outcomes. PROSPERO REGISTRATION NUMBER: CRD42016039188.

PMID- 29326187
TI  - Pilot study protocol to inform a future longitudinal study of ageing using linked
      administrative data: Healthy AGeing in Scotland (HAGIS).
AB  - INTRODUCTION: Population ageing is a welcome testament to improvements in the
      social, economic and health circumstances over the life course. However, these
      successes necessitate that we understand more about the pathways of ageing to
      plan and cost our health and social care services, to support our ageing
      population to live healthier for longer and to make adequate provisions for
      retirement. Longitudinal studies of ageing facilitate such understanding in many
      countries around the world. Scotland presently does not have a longitudinal study
      of ageing, despite dramatic increases to its ageing population and its poor
      health record. Healthy AGeing in Scotland (HAGIS) constitutes the launch of
      Scotland's first comprehensive longitudinal study of ageing. METHODS: A sample of
      1000 people aged 50+ years will be invited to take part in a household social
      survey. The innovative sampling procedure used administrative data to identify
      eligible households. Anonymised survey responses will be linked to administrative
      data. ETHICS AND DISSEMINATION: Ethics approval was obtained from the host
      institution for the study design and from the Public Benefits and Privacy Panel
      for administrative data linkage. Anonymised survey data will be deposited with
      the UK Data Service. A subset of survey data, harmonised with other global ageing
      studies, will be available via the Gateway to Global Aging platform. These data
      will enable powerful cross-country comparisons across the social, economic and
      health domains that will be relevant for national and international
      research.Research publications from the HAGIS team will be disseminated through
      journal articles and national and international conferences. The findings will
      support current and future research and policy debate on ageing populations.

PMID- 29326188
TI  - Managing cognitive impairment following stroke: protocol for a systematic review
      of non-randomised controlled studies of psychological interventions.
AB  - INTRODUCTION: Stroke is one of the primary causes of death and disability
      worldwide, leaving a considerable proportion of survivors with persistent
      cognitive and functional deficits. Despite the prevalence of poststroke cognitive
      impairment, there is no established treatment aimed at improving cognitive
      function following a stroke. Therefore, the aims of this systematic review are to
      identify psychological interventions intended to improve poststroke cognitive
      function and establish their efficacy. METHODS AND ANALYSIS: A systematic review
      of non-randomised controlled studies that investigated the efficacy of
      psychological interventions aimed at improving cognitive function in stroke
      survivors will be conducted. Electronic searches will be performed in the PubMed,
      Embase and PsycINFO databases, the search dating from the beginning of the index
      to February 2017. Reference lists of all identified relevant articles will be
      reviewed to identify additional studies not previously identified by the
      electronic search. Potential grey literature will be reviewed using Google
      Scholar. Titles and abstracts will be assessed for eligibility by one reviewer,
      with a random sample of 50% independently double-screened by second reviewers.
      Any discrepancies will be resolved through discussion, with referral to a third
      reviewer where necessary. Risk of bias will be assessed with the Risk of Bias in
      Non-randomized Studies of Interventions tool. Meta-analyses will be performed if
      studies are sufficiently homogeneous. This review will follow the Preferred
      Reporting Items for Systematic Reviews and Meta-Analyses statement. The quality
      of the evidence regarding cognitive function will be assessed according to the
      Grading of Recommendations Assessment, Development and Evaluation. ETHICS AND
      DISSEMINATION: This systematic review will collect secondary data only and as
      such ethical approval is not required. Findings will be disseminated through
      presentations and peer-reviewed publication. This review will provide information
      on the effectiveness of psychological interventions for poststroke cognitive
      impairment, identifying which psychological interventions are effective for
      improving poststroke cognitive function. PROSPERO REGISTRATION NUMBER:
      CRD42017069714.

PMID- 29326189
TI  - Period prevalence, risk factors and consequent injuries of falling among the
      Saudi elderly living in Riyadh, Saudi Arabia: a cross-sectional study.
AB  - OBJECTIVES: Approximately 28% to 35% of people aged 65 and over fall each year.
      The consequent injuries of falls are considered a major public health problem.
      Falls account for more than half of injury-related hospitalisations among old
      people. The aim of this study was to measure a 1-year period prevalence of
      falling among old people in Riyadh, Saudi Arabia. In addition, this study
      described the most common risk factors and consequent injuries of falls. SETTING
      AND PARTICIPANTS: A cross-sectional survey was carried out in Riyadh, using a
      convenient sampling. The targeted population were Saudi citizens who were 60
      years or above. Over a 6-month period, 1182 individuals were sampled (545 men and
      637 women). RESULTS: The 1-year prevalence of falling among old Saudis (>=60
      years) was 49.9%. Our results show that 74% of the participants who experienced
      falls had postfall injuries. Old participants who were uneducated and those with
      middle school certification were associated with falls (adjusted OR (aOR) 1.72;
      95% CI 1.15 to 2.56, aOR 1.81; 95% CI 1.15 to 2.85, respectively). Those who live
      in rented houses had a higher risk of falls. Interestingly, having a caregiver
      was significantly associated with more falls (aOR 1.39; 95% CI 1.08 to 1.79).
      However, not using any medications was significantly related to fewer falls. In
      addition, old individuals using walking aids were more likely to fall than those
      who did not. Participants who mentioned 'not having stressors were associated
      with less frequent falls (aOR 0.62; 95% CI 0.39 to 0.97). Cerebrovascular
      accidents were strongly associated with falls with an estimated OR of 2.75 (95%
      CI 1.18 to 6.43). Moreover, osteoporosis, poor vision and back pain were found to
      be predictors for falls among the elderly. CONCLUSION: 49.9% of elderly Saudis
      had experienced one or more falls during a 12-month period. Several preventable
      risk factors could be addressed by routine geriatric assessment. Research on the
      impact of these risk factors is needed.

PMID- 29326190
TI  - A qualitative study of patients' feedback about Outpatient Parenteral
      Antimicrobial Therapy (OPAT) services in Northern England: implications for
      service improvement.
AB  - OBJECTIVE: Outpatient parenteral antimicrobial therapy (OPAT) provides
      opportunities for improved cost savings, but in the UK, implementation is patchy
      and a variety of service models are in use. The slow uptake in the UK and Europe
      is due to a number of clinical, financial and logistical issues, including
      concern about patient safety. The measurement of patient experience data is
      commonly used to inform commissioning decisions, but these focus on functional
      aspects of services and fail to examine the relational aspects of care. This
      qualitative study examines patients' experiences of OPAT. DESIGN: In-depth,
      semistructured interviews. SETTING: Purposive sample of OPAT patients recruited
      from four acute National Health Service (NHS) Trusts in Northern England. These
      NHS Trusts between them represented both well-established and recently set-up
      services running nurse at home, hospital outpatient and/or self-administration
      models. PARTICIPANTS: We undertook 28 semistructured interviews and one focus
      group (n=4). RESULTS: Despite good patient outcomes, experiences were coloured by
      patients' personal situation and material circumstances. Many found looking after
      themselves at home more difficult than they expected, while others continued to
      work despite their infection. Expensive car parking, late running services and
      the inconvenience of waiting in for the nurse to arrive frustrated patients,
      while efficient services, staffed by nurses with the specialist skills needed to
      manage intravenous treatment had the opposite effect. Many patients felt a local,
      general practitioner or community health centre based service would resolve many
      of the practical difficulties that made OPAT inconvenient. Patients could find
      OPAT anxiety provoking but this could be ameliorated by staff taking the time to
      reassure patients and provide tailored information. CONCLUSION: Services
      configurations must accommodate the diversity of the local population. Poor
      communication can leave patients lacking the confidence needed to be a competent
      collaborator in their own care and affect their perceptions of the service.

PMID- 29326191
TI  - Establishing anchor-based minimally important differences (MID) with the EORTC
      quality-of-life measures: a meta-analysis protocol.
AB  - INTRODUCTION: As patient assessment of health-related quality of life (HRQOL) in
      cancer clinical trials has increased over the years, so has the need to attach
      meaningful interpretations to differences in HRQOL scores between groups and
      changes within groups. Determining what represents a minimally important
      difference (MID) in HRQOL scores is useful to clinicians, patients and
      researchers, and can be used as a benchmark for assessing the success of a
      healthcare intervention. Our objective is to provide an evidence-based protocol
      to determine MIDs for the European Organisation for Research and Treatment for
      Cancer Quality of life Questionnaire core 30 (EORTC QLQ-C30). We will mainly
      focus on MID estimation for group-level comparisons. Responder thresholds for
      individual-level change will also be estimated. METHODS AND ANALYSIS: Data will
      be derived from published phase II and III EORTC trials that used the QLQ-C30
      instrument, covering several cancer sites. We will use individual patient data to
      estimate MIDs for different cancer sites separately. Focus is on anchor-based
      methods. Anchors will be selected per disease site from available data. A disease
      oriented and methodological panel will provide independent guidance on anchor
      selection. We aim to construct multiple clinical anchors per QLQ-C30 scale and
      also to compare with several anchor-based methods. The effects of covariates, for
      example, gender, age, disease stage and so on, will also be investigated. We will
      examine how our estimated MIDs compare with previously published guidelines,
      hence further contributing to robust MID guidelines for the EORTC QLQ-C30. ETHICS
      AND DISSEMINATION: All patient data originate from completed clinical trials with
      mandatory written informed consent, approved by local ethical committees. Our
      findings will be presented at scientific conferences, disseminated via peer
      reviewed publications and also compiled in a MID 'blue book' which will be made
      available online on the EORTC Quality of Life Group website as a free guideline
      document.

PMID- 29326193
TI  - Patient satisfaction with hospital care and nurses in England: an observational
      study.
AB  - OBJECTIVES: To inform healthcare workforce policy decisions by showing how
      patient perceptions of hospital care are associated with confidence in nurses and
      doctors, nurse staffing levels and hospital work environments. DESIGN: Cross
      sectional surveys of 66 348 hospital patients and 2963 inpatient nurses. SETTING:
      Patients surveyed were discharged in 2010 from 161 National Health Service (NHS)
      trusts in England. Inpatient nurses were surveyed in 2010 in a sample of 46
      hospitals in 31 of the same 161 trusts. PARTICIPANTS: The 2010 NHS Survey of
      Inpatients obtained information from 50% of all patients discharged between June
      and August. The 2010 RN4CAST England Nurse Survey gathered information from
      inpatient medical and surgical nurses. MAIN OUTCOME MEASURES: Patient ratings of
      their hospital care, their confidence in nurses and doctors and other indicators
      of their satisfaction. Missed nursing care was treated as both an outcome measure
      and explanatory factor. RESULTS: Patients' perceptions of care are significantly
      eroded by lack of confidence in either nurses or doctors, and by increases in
      missed nursing care. The average number of types of missed care was negatively
      related to six of the eight outcomes-ORs ranged from 0.78 (95% CI 0.68 to 0.90)
      for excellent care ratings to 0.86 (95% CI 0.77 to 0.95) for medications
      completely explained-positively associated with higher patient-to-nurse ratios
      (b=0.15, 95% CI 0.10 to 0.19), and negatively associated with better work
      environments (b=-0.26, 95% CI -0.48 to -0.04). CONCLUSIONS: Patients' perceptions
      of hospital care are strongly associated with missed nursing care, which in turn
      is related to poor professional nurse (RN) staffing and poor hospital work
      environments. Improving RN staffing in NHS hospitals holds promise for enhancing
      patient satisfaction.

PMID- 29326192
TI  - Evidence for sample selection effect and Hawthorne effect in behavioural HIV
      prevention trial among young women in a rural South African community.
AB  - OBJECTIVES: We examined the potential influence of both sample selection effects
      and Hawthorne effects in the behavioural HIV Prevention Trial Network 068 study,
      designed to examine whether cash transfers conditional on school attendance
      reduce HIV acquisition in young South African women. We explored whether school
      enrolment among study participants differed from the underlying population, and
      whether differences existed at baseline (sample selection effect) or arose during
      study participation (Hawthorne effect). METHODS: We constructed a cohort of 3889
      young women aged 11-20 years using data from the Agincourt Health and socio
      Demographic Surveillance System. We compared school enrolment in 2011 (trial
      start) and 2015 (trial end) between those who did (n=1720) and did not (n=2169)
      enrol in the trial. To isolate the Hawthorne effect, we restricted the cohort to
      those enrolled in school in 2011. RESULTS: In 2011, trial participants were
      already more likely to be enrolled in school (99%) compared with non-participants
      (93%). However, this association was attenuated with covariate adjustment
      (adjusted risk difference (aRD) (95% CI): 2.9 (- 0.7 to 6.5)). Restricting to
      those enrolled in school in 2011, trial participants were also more likely to be
      enrolled in school in 2015 (aRD (95% CI): 4.9 (1.5 to 8.3)). The strength of
      associations increased with age. CONCLUSIONS: Trial participants across both
      study arms were more likely to be enrolled in school than non-participants. Our
      findings suggest that both sample selection and Hawthorne effects may have
      diminished the differences in school enrolment between study arms, a plausible
      explanation for the null trial findings. The Hawthorne-specific findings generate
      hypotheses for how to structure school retention interventions to prevent HIV.

PMID- 29326194
TI  - Association of erythrocyte parameters with metabolic syndrome in the Pearl River
      Delta region of China: a cross sectional study.
AB  - OBJECTIVE: Increasing studies have reported that erythrocyte parameters,
      including red blood cells (RBCs), haematocrit (HCT), haemoglobin (Hb) and red
      blood cell distribution width (RDW), are associated with metabolic syndrome
      (MetS) in adults worldwide. However, the association, stratified by sex, remains
      to be elucidated, particularly in the Pearl River Delta region of China.
      Therefore, our aim was to explore the association of erythrocyte parameters with
      MetS, stratified by sex, in the Pearl River Delta region of China. METHODS: In
      this cross sectional study, 2161 men and 2511 women were enrolled. MetS was
      diagnosed using a modified version of the Adult Treatment Panel III criteria.
      Logistic regression analyses were performed to calculate adjusted ORs of
      erythrocyte parameters associated with MetS stratified by sex. RESULTS: The
      prevalence of MetS was higher in women than in men (35.2%vs26.7%). RBC, HCT, Hb
      and RDW values increased linearly with the number of MetS components from 0 to 5
      identified in both men and women. Among men, the ORs of MetS risk increased
      across the tertiles of Hb (Q2: OR=1.921, 95% CI=1.170 to 3.151; Q3: OR=1.992,
      95%CI=1.198 to 3.312). Men in the highest tertiles of RDW had a 2.752-fold
      increased risk of suffering from MetS compared with those in the reference group.
      Among women, the ORs of MetS risk also increased across the tertiles of Hb (Q2:
      OR=1.538, 95%CI=1.008 to 2.348; Q3: OR=1.665, 95%CI=1.075 to 2.578). Women in the
      highest tertiles of RBC had a 1.718-fold increased risk of experiencing MetS
      compared with those in the reference group. CONCLUSIONS: MetS was more prevalent
      in women than in men. The association between erythrocyte parameters and MetS
      differed between the sexes. RBC and Hb were identified as risk factors for MetS
      in women and Hb and RDW as risk factors in men.

PMID- 29326195
TI  - Why do GPs leave direct patient care and what might help to retain them? A
      qualitative study of GPs in South West England.
AB  - OBJECTIVE: To identify factors influencing general practitioners' (GPs')
      decisions about whether or not to remain in direct patient care in general
      practice and what might help to retain them in that role. DESIGN: Qualitative, in
      depth, individual interviews exploring factors related to GPs leaving, remaining
      in and returning to direct patient care. SETTING: South West England, UK.
      PARTICIPANTS: 41 GPs: 7 retired; 8 intending to take early retirement; 11 who
      were on or intending to take a career break; 9 aged under 50 years who had left
      or were intending to leave direct patient care and 6 who were not intending to
      leave or to take a career break. Plus 19 stakeholders from a range of primary
      care-related professional organisations and roles. RESULTS: Reasons for leaving
      direct patient care were complex and based on a range of job-related and
      individual factors. Three key themes underpinned the interviewed GPs' thinking
      and rationale: issues relating to their personal and professional identity and
      the perceived value of general practice-based care within the healthcare system;
      concerns regarding fear and risk, for example, in respect of medical litigation
      and managing administrative challenges within the context of increasingly complex
      care pathways and environments; and issues around choice and volition in respect
      of personal social, financial, domestic and professional considerations. These
      themes provide increased understanding of the lived experiences of working in
      today's National Health Service for this group of GPs. CONCLUSION: Future
      policies and strategies aimed at retaining GPs in direct patient care should
      clarify the role and expectations of general practice and align with GPs'
      perception of their own roles and identity; demonstrate to GPs that they are
      valued and listened to in planning delivery of the UK healthcare; target GPs'
      concerns regarding fear and risk, seeking to reduce these to manageable levels
      and give GPs viable options to support them to remain in direct patient care.

PMID- 29326196
TI  - Young adults' perspectives on living with kidney failure: a systematic review and
      thematic synthesis of qualitative studies.
AB  - INTRODUCTION: Young adults fare worse than younger adolescents or older adults on
      a broad range of health indicators. Those with a chronic illness such as renal
      failure are a particularly vulnerable group, who experience poor outcomes
      compared with both children and older adults. Understanding how being in receipt
      of renal replacement therapy (RRT) affects the lives of young adults might help
      us to better prepare and support these individuals for and on RRT, and improve
      outcomes. This study aimed to synthesise research describing young adults'
      experiences of the psychosocial impact of kidney failure and RRT. DESIGN: A
      systematic literature review identified qualitative research reporting the
      perspectives of people aged 16-30 years receiving RRT on the psychosocial impact
      of renal failure. Electronic databases (including Medline/EMBASE/PsycINFO/ASSIA)
      were searched to November 2017 for full-text papers. The transparency of
      reporting of each study was assessed using the Consolidated Criteria for
      Reporting Qualitative Health Research (COREQ) framework. Quality was assessed
      using the Critical Appraisal Skills Programme qualitative checklist. An inductive
      thematic synthesis was undertaken. PARTICIPANTS: Seven studies from five
      different countries were included, comprising 123 young adults receiving RRT.
      RESULTS: Comprehensiveness of reporting was variable: studies reported 9-22 of
      the 32 COREQ-checklist items.Three global themes about the impact of kidney
      failure on young adults were identified: (1) difference desiring normality, (2)
      thwarted or moderated dreams and ambitions, and (3) uncertainty and liminality.
      These reflected five organising themes: (1) physical appearance and body image,
      (2) activity and participation, (3) educational disruption and underachievement,
      (4) career ambitions and employment difficulties, and (5) social isolation and
      intimate relationships. CONCLUSIONS: Across different countries and different
      healthcare settings, young adults on RRT experience difference and liminality,
      even after transplantation. Tailored social and psychological support is required
      to allow young adults to experience wellness while in receipt of RRT, and not
      have life on hold.

PMID- 29326197
TI  - PARENTS 2 study protocol: pilot of Parents' Active Role and ENgagement in the
      review of Their Stillbirth/perinatal death.
AB  - BACKGROUND: The perinatal mortality review meeting that takes place within the
      hospital following a stillbirth or neonatal death enables clinicians to learn
      vital lessons to improve care for women and their families for the future. Recent
      evidence suggests that parents are unaware that a formal review following the
      death of their baby takes place. Many would welcome the opportunity to feedback
      into the meeting itself. Parental involvement in the perinatal mortality review
      meeting has the potential to improve patient satisfaction, drive improvements in
      patient safety and promote an open culture within healthcare. Yet evidence on the
      feasibility of involving bereaved parents in the review process is lacking. This
      paper describes the protocol for the Parents' Active Role and Engangement iN the
      review of their Stillbirth/perinatal death study (PARENTS 2) , whereby healthcare
      professionals' and stakeholders' perceptions of parental involvement will be
      investigated, and parental involvement in the perinatal mortality review will be
      piloted and evaluated at two hospitals. METHODS AND ANALYSIS: We will investigate
      perceptions of parental involvement in the perinatal mortality review process by
      conducting four focus groups. A three-round modified Delphi technique will be
      employed to gain a consensus on principles of parental involvement in the
      perinatal mortality review process. We will use three sequential rounds,
      including a national consensus meeting workshop with experts in stillbirth,
      neonatal death and bereavement care, and a two-stage anonymous online
      questionnaire. We will pilot a new perinatal mortality review process with
      parental involvement over a 6-month study period. The impact of the new process
      will be evaluated by assessing parents' experiences of their care and parents'
      and staff perceptions of their involvement in the process by conducting further
      focus groups and using a Parent Generated Index questionnaire. ETHICS AND
      DISSEMINATION: This study has ethical approval from the UK Health Research
      Authority. We will disseminate the findings through national and international
      conferences and international peer-reviewed journals.

PMID- 29326198
TI  - Genome Sequence of a Novel Strain of a Phasi Charoen-Like Virus Identified in
      Zhanjiang, China.
AB  - Here, we report the genome sequence of a novel strain of a Phasi Charoen-like
      virus, isolated from Aedes aegypti mosquitoes caught in Zhanjiang province of
      China. Phylogenetic analysis suggested that this virus belongs to a new genus,
      Goukovirus, in the family Bunyaviridae This is the first reported genome sequence
      of a Phasi Charoen-like virus identified in China.

PMID- 29326200
TI  - Complete Genome Sequence of a Bacteriophage, pVco-5, That Infects Vibrio
      coralliilyticus, Which Causes Bacillary Necrosis in Pacific Oyster (Crassostrea
      gigas) Larvae.
AB  - We report here the complete genome sequence of the Vibrio coralliilyticus
      specific phage pVco-5, a double-stranded DNA virus isolated from an oyster
      hatchery tank. Vibrio coralliilyticus causes bacillary necrosis in marine bivalve
      larvae; hence, phage pVco-5 could be used to prevent V. coralliilyticus
      infections in these larvae.

PMID- 29326199
TI  - Genome Sequences of Four Cluster P Mycobacteriophages.
AB  - Four bacteriophages infecting Mycobacterium smegmatis mc2155 (three belonging to
      subcluster P1 and one belonging to subcluster P2) were isolated from soil and
      sequenced. All four phages are similar in the left arm of their genomes, but the
      P2 phage differs in the right arm. All four genomes contain features of temperate
      phages.

PMID- 29326202
TI  - Genome Sequence of Galleria mellonella (Greater Wax Moth).
AB  - The larvae of the greater wax moth, Galleria mellonella, are pests of active
      beehives. In infection biology, these larvae are playing a more and more
      attractive role as an invertebrate host model. Here, we report on the first
      genome sequence of Galleria mellonella.

PMID- 29326201
TI  - Eight Genome Sequences of Cluster BE1 Phages That Infect Streptomyces Species.
AB  - Cluster BE1 Streptomyces bacteriophages belong to the Siphoviridae, with genome
      sizes over 130 kbp, and they contain direct terminal repeats of approximately 11
      kbp. Eight newly isolated closely related cluster BE1 phages contain 43 to 48
      tRNAs, one transfer-messenger RNA (tmRNA), and 216 to 236 predicted open reading
      frames (ORFs), but few of their genes are shared with other phages, including
      those infecting Streptomyces species.

PMID- 29326203
TI  - High-Quality Whole-Genome Sequences for 21 Enterotoxigenic Escherichia coli
      Strains Generated with PacBio Sequencing.
AB  - Enterotoxigenic Escherichia coli (ETEC) is an important diarrheagenic pathogen.
      We report here the high-quality whole-genome sequences of 21 ETEC strains
      isolated from patients in the United States, international diarrheal surveillance
      studies, and cruise ship outbreaks.

PMID- 29326204
TI  - Draft Genome Sequence of Brevibacillusreuszeri Strain NIT02, Isolated from a
      Laundered Rental Cloth Hot Towel.
AB  - Brevibacillus reuszeri is a Gram-positive spore-forming bacterium. Here, we
      present the draft genome sequence of Brevibacillus reuszeri strain NIT02, which
      was isolated from a laundered rental cloth hot towel.

PMID- 29326205
TI  - Complete Genome Sequence of the Escherichia coli Phage Ayreon.
AB  - We report the whole-genome sequence of a new Escherichia coli temperate phage,
      Ayreon, comprising a linear double-stranded DNA (dsDNA) genome of 44,708 bp.

PMID- 29326206
TI  - Whole-Genome Draft Sequences of Nine Asymptomatic Escherichia coli Bacteriuria
      Isolates from Diabetic Patients.
AB  - Escherichia coli can colonize the urinary bladder without causing a disease
      response in the host. This asymptomatic bacteriuria (ABU) can protect against
      recurrent symptomatic urinary tract infection by virulent bacteria. Here, we
      report the whole-genome sequences of nine E. coli ABU isolates from diabetic
      patients.

PMID- 29326207
TI  - Complete Genome Sequence of Bacteriophage St11Ph5, Which Infects Uropathogenic
      Escherichia coli Strain up11.
AB  - Bacteriophage St11Ph5 was isolated from a sewage sample on a particularly phage
      resistant uropathogenic Escherichia coli (UPEC) up11 host strain. It appeared to
      be closely related to bacteriophage G7C, isolated from horse feces; however, it
      carries a highly divergent host recognition module.

PMID- 29326208
TI  - Draft Genome Sequence of the Filamentous Fungus Hypoxylon pulicicidum ATCC 74245.
AB  - Hypoxylon pulicicidum strain MF5954 (ATCC 74245) (formerly classified as
      Nodulisporium sp.) is a filamentous fungal species known for its production of
      the secondary metabolite nodulisporic acid A. We present here the 41.5-Mb draft
      genome sequence for this organism.

PMID- 29326209
TI  - Complete Genome Sequence of Escherichia coli Strain WG5.
AB  - Escherichia coli strain WG5 is a widely used host for phage detection, including
      somatic coliphages employed as standard ISO method 10705-1 (2000). Here, we
      present the complete genome sequence of a commercial E. coli WG5 strain.

PMID- 29326210
TI  - Complete Genome Sequencing of Acinetobacter sp. Strain LoGeW2-3, Isolated from
      the Pellet of a White Stork, Reveals a Novel Class D Beta-Lactamase Gene.
AB  - Whole-genome sequencing of Acinetobacter sp. strain LoGeW2-3, isolated from the
      pellet of a white stork (Ciconia ciconia), reveals the presence of a plasmid of
      179,399 bp encoding a CRISPR-Cas (clustered regularly interspaced short
      palindromic repeats and associated genes) system of the I-F type, and the
      chromosomally encoded novel class D beta-lactamase OXA-568.

PMID- 29326211
TI  - Draft Whole-Genome Sequence of Deinococcus sp. UR1, a Putative Novel Species
      Isolated from an External Stainless Steel Surface in the Canadian Prairies.
AB  - Deinococcus sp. strain UR1, a resilient bacterium isolated from the surface of a
      stainless steel sign located on the University of Regina campus in Saskatchewan,
      Canada, was sequenced to 56-fold coverage to produce 73 contigs with a consensus
      length of 4,472,838 bp and a G+C content of 69.37%.

PMID- 29326212
TI  - Complete Genome Sequence of Thermoanaerobacterium sp. Strain RBIITD, a Butyrate-
      and Butanol-Producing Thermophile.
AB  - Thermoanaerobacterium sp. strain RBIITD was isolated from contaminated rich
      growth medium at 55 degrees C in an anaerobic chamber. It primarily produces
      butyrate as a fermentation product from plant biomass-derived sugars. The whole
      genome sequence of the strain is 3.4 Mbp, with 3,444 genes and 32.48% GC content.

PMID- 29326213
TI  - Complete Genome Sequence of Chryseobacterium camelliae Dolsongi-HT1, a Green Tea
      Isolate with Keratinolytic Activity.
AB  - The complete genome sequence of Chryseobacterium camelliae Dolsongi-HT1 is
      reported here. C. camelliae Dolsongi-HT1, having keratinolytic activity, was
      isolated from green tea leaves in the Dolsongi tea garden in Jeju, South Korea.
      The strain Dolsongi-HT1 has 28 candidate protease genes, which may be utilized in
      further studies and industrial applications of keratinase.

PMID- 29326214
TI  - Whole-Genome Sequences of Brucella melitensis Strain QH61, Isolated from Yak in
      Qinghai, China.
AB  - The facultative intracellular Gram-negative bacterium Brucella melitensis causes
      brucellosis in domestic and wild mammals. Brucella melitensis QH61 was isolated
      from a yak suffering from abortion in 2015 in Qinghai, China. Here, we report the
      whole-genome sequence of B. melitensis strain QH61.

PMID- 29326215
TI  - Draft Genome Sequence of Talaromyces adpressus.
AB  - Here we present the draft genome sequence of the fungus Talaromyces adpressus A
      T1C-84X (=CBS 142503). This strain was isolated from lignocellulosic biomass of
      Arundo donax during biodegradation under natural conditions in the Gussone Park
      of the Royal Palace of Portici, Naples, Italy.

PMID- 29326216
TI  - Draft Genome Sequence of Prochlorococcus marinus Strain XMU1401, Isolated from
      the Western Tropical North Pacific Ocean.
AB  - Prochlorococcus marinus is the most abundant photosynthetic organism in the
      tropical and subtropical oceans. Here, we report the draft genome sequence of
      Prochlorococcus marinus XMU1401, which was isolated from the Western Tropical
      North Pacific Ocean.

PMID- 29326217
TI  - Draft Genome Sequences of Bifidobacterium Strains N4G05 and N5G01, Isolated from
      the Human Vaginal Microbiome.
AB  - We report here the draft genome sequences of Bifidobacterium strains N4G05 and
      N5G01, isolated from the human vaginal microbiome. Genome sequences were obtained
      by de novo assembly from high-quality reads. Both strains were closely related to
      Bifidobacterium kashiwanohense based on barcode marker sequences and average
      nucleotide identity analysis.

PMID- 29326218
TI  - First Draft Genome Sequences of Two Bartonella tribocorum Strains from Laos and
      Cambodia.
AB  - Bartonella tribocorum is a Gram-negative bacterium known to infect animals, and
      rodents in particular, throughout the world. In this report, we present the draft
      genome sequences of two strains of B. tribocorum isolated from the blood of a
      rodent in Laos and a shrew in Cambodia.

PMID- 29326219
TI  - Draft Genome Sequence of the Fungus Lecanicillium psalliotae Strain HWLR35,
      Isolated from a Wheat Leaf Infected with Leaf Rust (Caused by Puccinia
      triticina).
AB  - Lecanicillium psalliotae is an entomopathogenic, mycoparasitical, and
      nematophagous fungus known to produce antibiotic and antifungal compounds. Here,
      we report the first 36-Mb draft genome sequence of L. psalliotae strain HWLR35.
      The draft genome contains 197 scaffolds and is predicted to have 11,009 protein
      coding genes.

PMID- 29326220
TI  - Draft Genome Sequence of Saccharomycopsis fermentans CBS 7830, a Predacious Yeast
      Belonging to the Saccharomycetales.
AB  - Saccharomycopsis fermentans is an ascomycetous necrotrophic fungal pathogen that
      penetrates and kills fungal prey cells via targeted penetration pegs. Here, we
      report the draft genome sequence and scaffold assembly of this mycoparasite.

PMID- 29326221
TI  - Genome Sequences of Acholeplasma laidlawii Strains with Increased Resistance to
      Tetracycline and Melittin.
AB  - Acholeplasma laidlawii is a well-suited model for studying the molecular basis
      for adapting mollicutes to environmental conditions. Here, we present the whole
      genome sequences of two strains of A. laidlawii with increased resistance to
      tetracycline and melittin.

PMID- 29326222
TI  - Genome Sequence of Actinobacillus seminis Strain ATCC 15768, a Reference Strain
      of Ovine Pathogens That Causes Infections in Reproductive Organs.
AB  - The draft genome sequence of Actinobacillus seminis strain ATCC 15768 is reported
      here. The genome comprises 22 contigs corresponding to 2.36 Mb with 40.7% G+C
      content and contains several genes related to virulence, including a putative RTX
      protein.

PMID- 29326223
TI  - Genome Sequence of a Lethal Strain of Xylem-Invading Verticillium nonalfalfae.
AB  - Verticillium nonalfalfae, a soilborne vascular phytopathogenic fungus, causes
      wilt disease in several crop species. Of great concern are outbreaks of highly
      aggressive V. nonalfalfae strains, which cause a devastating wilt disease in
      European hops. We report here the genome sequence and annotation of V.
      nonalfalfae strain T2, providing genomic information that will allow better
      understanding of the molecular mechanisms underlying the development of highly
      aggressive strains.

PMID- 29326224
TI  - Draft Genome Sequence of Megamonas funiformis Strain Marseille-P3344, Isolated
      from a Human Fecal Microbiota.
AB  - In this article, we present the draft genome sequence of Megamonas funiformis
      strain Marseille-P3344, isolated from a human fecal sample. The genome described
      here is composed of 2,464,704 nucleotides, with 2,230 protein-coding genes and 76
      RNA genes.

PMID- 29326225
TI  - Genomic Insights into Biofilm-Forming Enterococcus faecalis SK460 Isolated from a
      Chronic Diabetic Ulcer Patient.
AB  - Enterococcus faecalis is recognized as one of the leading pathogens causing
      nosocomial infections. Here we report a draft genome sequence of Enterococcus
      faecalis SK460, isolated from a chronic diabetic foot ulcer patient. This strain
      exhibits various biofilm-associated genes, virulence genes, and antibiotic
      resistance genes related to aminoglycoside, macrolide, and tetracycline
      resistance.

PMID- 29326226
TI  - Draft Genome Sequence of Chryseobacterium mucoviscidosis sp. nov. Strain VT16-26,
      Isolated from the Bronchoalveolar Lavage Fluid of a Patient with Cystic Fibrosis.
AB  - We report here the draft genome sequence of Chryseobacterium mucoviscidosis VT16
      26, a novel bacterium isolated from the lungs of a patient with cystic fibrosis.
      The genome was composed of 4,403,956 bp and had 36.2% G+C content. We detected
      4,048 genes with predicted protein-coding functions, including those associated
      with antibiotic resistance and virulence.

PMID- 29326227
TI  - Draft Genome Sequence of Lactobacillus fermentum NCDC 400, Isolated from a
      Traditional Indian Dairy Product.
AB  - We announce here the draft genome sequence of Lactobacillus fermentum NCDC 400, a
      potential probiotic strain isolated from a traditional Indian dairy product. The
      genome size of Lactobacillus fermentum NCDC 400 is 1.89 Mb, and the assembled
      sequence consists of 185 contigs joined into 138 scaffolds.

PMID- 29326228
TI  - Bringing Social Context Into the Conversation About Pediatric Long-term
      Ventilation.

PMID- 29326229
TI  - Genomic Understanding of an Infectious Brain Disease from the Desert.
AB  - Rhinocladiella mackenziei accounts for the majority of fungal brain infections in
      the Middle East, and is restricted to the arid climate zone between Saudi Arabia
      and Pakistan. Neurotropic dissemination caused by this fungus has been reported
      in immunocompromised, but also immunocompetent individuals. If untreated, the
      infection is fatal. Outside of humans, the environmental niche of R. mackenziei
      is unknown, and the fungus has been only cultured from brain biopsies. In this
      paper, we describe the whole-genome resequencing of two R. mackenziei strains
      from patients in Saudi Arabia and Qatar. We assessed intraspecies variation and
      genetic signatures to uncover the genomic basis of the pathogenesis, and
      potential niche adaptations. We found that the duplicated genes (paralogs) are
      more susceptible to accumulating significant mutations. Comparative genomics with
      other filamentous ascomycetes revealed a diverse arsenal of genes likely engaged
      in pathogenicity, such as the degradation of aromatic compounds and iron
      acquisition. In addition, intracellular accumulation of trehalose and choline
      suggests possible adaptations to the conditions of an arid climate region.
      Specifically, protein family contractions were found, including short-chain
      dehydrogenase/reductase SDR, the cytochrome P450 (CYP) (E-class), and the G
      protein beta WD-40 repeat. Gene composition and metabolic potential indicate
      extremotolerance and hydrocarbon assimilation, suggesting a possible
      environmental habitat of oil-polluted desert soil.

PMID- 29326230
TI  - Base-Resolution Analysis of DNA Methylation Patterns Downstream of Dnmt3a in
      Mouse Naive B Cells.
AB  - The DNA methyltransferase, Dnmt3a, is dynamically regulated throughout mammalian
      B cell development and upon activation by antigenic stimulation. Dnmt3a
      inactivation in hematopoietic stem cells has been shown to drive B cell-related
      malignancies, including chronic lymphocytic leukemia, and associates with
      specific DNA methylation patterns in transformed cells. However, while it is
      clear that inactivation of Dnmt3a in hematopoietic stem cells has profound
      functional effects, the consequences of Dnmt3a inactivation in cells of the B
      lineage are unclear. To assess whether loss of Dnmt3a at the earliest stages of B
      cell development lead to DNA methylation defects that might impair function, we
      selectively inactivated Dnmt3a early in mouse B cell development and then
      utilized whole genome bisulfite sequencing to generate base-resolution profiles
      of Dnmt3a+/+ and Dnmt3a-/- naive splenic B cells. Overall, we find that global
      methylation patterns are largely consistent between Dnmt3a+/+ and Dnmt3a-/- naive
      B cells, indicating a minimal functional effect of DNMT3A in mature B cells.
      However, loss of Dnmt3a induced 449 focal DNA methylation changes, dominated by
      loss-of-methylation events. Regions found to be hypomethylated in Dnmt3a-/- naive
      splenic B cells were enriched in gene bodies of transcripts expressed in B cells,
      a fraction of which are implicated in B cell-related disease. Overall, the
      results from this study suggest that factors other than Dnmt3a are the major
      drivers for methylome maintenance in B cell development.

PMID- 29326232
TI  - Future of nonnucleoside reverse transcriptase inhibitors.

PMID- 29326233
TI  - Partitioning aggression.

PMID- 29326231
TI  - Linked networks for learning and expressing location-specific threat.
AB  - Learning locations of danger within our environment is a vital adaptive ability
      whose neural bases are only partially understood. We examined fMRI brain activity
      while participants navigated a virtual environment in which flowers appeared and
      were "picked." Picking flowers in the danger zone (one-half of the environment)
      predicted an electric shock to the wrist (or "bee sting"); flowers in the safe
      zone never predicted shock; and household objects served as controls for neutral
      spatial memory. Participants demonstrated learning with shock expectancy ratings
      and skin conductance increases for flowers in the danger zone. Patterns of brain
      activity shifted between overlapping networks during different task stages.
      Learning about environmental threats, during flower approach in either zone,
      engaged the anterior hippocampus, amygdala, and ventromedial prefrontal cortex
      (vmPFC), with vmPFC-hippocampal functional connectivity increasing with
      experience. Threat appraisal, during approach in the danger zone, engaged the
      insula and dorsal anterior cingulate (dACC), with insula-hippocampal functional
      connectivity. During imminent threat, after picking a flower, this pattern was
      supplemented by activity in periaqueductal gray (PAG), insula-dACC coupling, and
      posterior hippocampal activity that increased with experience. We interpret these
      patterns in terms of multiple representations of spatial context (anterior
      hippocampus); specific locations (posterior hippocampus); stimuli (amygdala);
      value (vmPFC); threat, both visceral (insula) and cognitive (dACC); and defensive
      behaviors (PAG), interacting in different combinations to perform the functions
      required at each task stage. Our findings illuminate how we learn about location
      specific threats and suggest how they might break down into overgeneralization or
      hypervigilance in anxiety disorders.

PMID- 29326234
TI  - Toward a unifying theory of biodiversity.

PMID- 29326235
TI  - Predicting tipping points in complex environmental systems.

PMID- 29326236
TI  - Celebrating 35 Years of the AJNR: January 1983 edition.

PMID- 29326237
TI  - An ulcer on the nipple.

PMID- 29326238
TI  - Further points to consider after primary percutaneous coronary intervention.

PMID- 29326239
TI  - What is positionality and should it be expressed in quantitative studies?
AB  - Although we are increasingly reaping the benefits of qualitative studies, their
      approach and that of quantitative studies remain rather separate. Emergency
      medicine practitioners thrive off research in context as we deal with such an
      undifferentiated population however quantitative 'hard-science' work is
      conspicuous for its absence of positionality. This contrasts strongly with the
      way in which qualitative research, within the domain of so-called soft-science
      literature, uses positionality as an integral element of the research process.
      Without contextualising the researcher and research environment in qualitative
      studies, often the meaning of any research output is lost. What follows is that
      positionality does not undermine the truth of such research, instead it defines
      the boundaries within which the research was produced.  The absence of
      positionality when considered alongside the notion of bias, may challenge the
      quantitative idea of validity.

PMID- 29326241
TI  - Upsurge in attacks on hospitals in Syria condemned.

PMID- 29326240
TI  - Neuropsychological assessment in epilepsy.
AB  - The role of the neuropsychological assessment in the management of people with
      epilepsy has evolved considerably over the past 25 years. This paper describes
      some of the most common applications of a neuropsychological assessment in the
      diagnosis, management and treatment of people with epilepsy. It describes the
      factors that influence the interpretation of neuropsychological test scores in
      this patient group and outlines the limitations of the investigation. It gives
      guidelines for the optimal timing of a referral, together with timelines and
      indications for reassessment, and provides a checklist to help the referring
      clinician get the most from a neuropsychological assessment for their patients
      with epilepsy.

PMID- 29326242
TI  - Biased Agonism in Drug Discovery-Is It Too Soon to Choose a Path?
AB  - A single receptor can activate multiple signaling pathways that have distinct or
      even opposite effects on cell function. Biased agonists stabilize receptor
      conformations preferentially stimulating one of these pathways, and therefore
      allow a more targeted modulation of cell function and treatment of disease.
      Dedicated development of biased agonists has led to promising drug candidates in
      clinical development, such as the G protein-biased u opioid receptor agonist
      oliceridine. However, leveraging the theoretical potential of biased agonism for
      drug discovery faces several challenges. Some of these challenges are technical,
      such as techniques for quantitative analysis of bias and development of suitable
      screening assays; others are more fundamental, such as the need to robustly
      identify in a very early phase which cell type harbors the cellular target of the
      drug candidate, which signaling pathway leads to the desired therapeutic effect,
      and how these pathways may be modulated in the disease to be treated. We conclude
      that biased agonism has potential mainly in the treatment of conditions with a
      well-understood pathophysiology; in contrast, it may increase effort and
      commercial risk under circumstances where the pathophysiology has been less well
      defined, as is the case with many highly innovative treatments.

PMID- 29326244
TI  - Gene therapy comes of age.
AB  - After almost 30 years of promise tempered by setbacks, gene therapies are rapidly
      becoming a critical component of the therapeutic armamentarium for a variety of
      inherited and acquired human diseases. Gene therapies for inherited immune
      disorders, hemophilia, eye and neurodegenerative disorders, and lymphoid cancers
      recently progressed to approved drug status in the United States and Europe, or
      are anticipated to receive approval in the near future. In this Review, we
      discuss milestones in the development of gene therapies, focusing on direct in
      vivo administration of viral vectors and adoptive transfer of genetically
      engineered T cells or hematopoietic stem cells. We also discuss emerging genome
      editing technologies that should further advance the scope and efficacy of gene
      therapy approaches.

PMID- 29326243
TI  - Concentrative Transport of Antifolates Mediated by the Proton-Coupled Folate
      Transporter (SLC46A1); Augmentation by a HEPES Buffer.
AB  - The proton-coupled folate transporter (PCFT) is ubiquitously expressed in solid
      tumors to which it delivers antifolates, particularly pemetrexed, into cancer
      cells. Studies of PCFT-mediated transport, to date, have focused exclusively on
      the influx of folates and antifolates. This article addresses the impact of PCFT
      on concentrative transport, critical to the formation of the active polyglutamate
      congeners, and at pH levels relevant to the tumor microenvironment. An HeLa
      derived cell line was employed, in which folate-specific transport was mediated
      exclusively by PCFT. At pH 7.0, there was a substantial chemical gradient for
      methotrexate that decreased as the extracellular pH was increased. A chemical
      gradient was still detected at pH 7.4 in the usual HEPES-based transport buffer
      in contrast to what was observed in a bicarbonate/CO2-buffered medium. This
      antifolate gradient correlated with an alkaline intracellular pH in the former
      (pH 7.85), but not the latter (pH 7.39), buffer and was abolished by the
      protonophore carbonyl cyanide-4-(trifluoromethoxy)phenylhydrazone. The gradient
      in HEPES buffer at pH 7.4 was the result of the activity of Na+/H+ exchanger(s);
      it was eliminated by inhibitors of Na+/H+ exchanger (s) or Na+/K+ ATPase. An
      antifolate chemical gradient was also detected in bicarbonate buffer at pH 6.9
      versus 7.4, also suppressed by carbonyl cyanide-4
      (trifluoromethoxy)phenylhydrazone. When the membrane potential is considered,
      PCFT generates substantial transmembrane electrochemical-potential gradients at
      extracellular pH levels relevant to the tumor microenvironment. The augmentation
      of intracellular pH, when cells are in a HEPES buffer, should be taken into
      consideration in studies that encompass all proton-coupled transporter families.

PMID- 29326246
TI  - Frankenstein lives on.

PMID- 29326245
TI  - Fatty acyl recognition and transfer by an integral membrane S-acyltransferase.
AB  - DHHC (Asp-His-His-Cys) palmitoyltransferases are eukaryotic integral membrane
      enzymes that catalyze protein palmitoylation, which is important in a range of
      physiological processes, including small guanosine triphosphatase (GTPase)
      signaling, cell adhesion, and neuronal receptor scaffolding. We present crystal
      structures of two DHHC palmitoyltransferases and a covalent intermediate mimic.
      The active site resides at the membrane-cytosol interface, which allows the
      enzyme to catalyze thioester-exchange chemistry by using fatty acyl-coenzyme A
      and explains why membrane-proximal cysteines are candidates for palmitoylation.
      The acyl chain binds in a cavity formed by the transmembrane domain. We propose a
      mechanism for acyl chain-length selectivity in DHHC enzymes on the basis of
      cavity mutants with preferences for shorter and longer acyl chains.

PMID- 29326248
TI  - DOE pushes for useful quantum computing.

PMID- 29326249
TI  - In Pakistan, surveillance for polio reveals a paradox.

PMID- 29326250
TI  - Earth scientists list top priorities for space missions.

PMID- 29326251
TI  - Cuba's 100-year plan for climate change.

PMID- 29326252
TI  - Cliffs of ice spied on Mars.

PMID- 29326253
TI  - The long shadow of Frankenstein.

PMID- 29326254
TI  - How a horror story haunts science.

PMID- 29326255
TI  - Creating a modern monster.

PMID- 29326256
TI  - Taming the monsters of tomorrow.

PMID- 29326257
TI  - A glossary of Frankenwords.

PMID- 29326258
TI  - Detecting the building blocks of aromatics.

PMID- 29326259
TI  - Improbable Big Birds.

PMID- 29326260
TI  - Malaria parasite evolution in a test tube.

PMID- 29326262
TI  - Coherent excitations revealed and calculated.

PMID- 29326261
TI  - TRPM channels come into focus.

PMID- 29326263
TI  - Silencing stemness in T cell differentiation.

PMID- 29326264
TI  - Global science for city policy.

PMID- 29326265
TI  - The next generation's Frankenstein films.

PMID- 29326266
TI  - The epigenetic control of stemness in CD8+ T cell fate commitment.
AB  - After priming, naive CD8+ T lymphocytes establish specific heritable
      transcription programs that define progression to long-lasting memory cells or to
      short-lived effector cells. Although lineage specification is critical for
      protection, it remains unclear how chromatin dynamics contributes to the control
      of gene expression programs. We explored the role of gene silencing by the
      histone methyltransferase Suv39h1. In murine CD8+ T cells activated after
      Listeria monocytogenes infection, Suv39h1-dependent trimethylation of histone H3
      lysine 9 controls the expression of a set of stem cell-related memory genes.
      Single-cell RNA sequencing revealed a defect in silencing of stem/memory genes
      selectively in Suv39h1-defective T cell effectors. As a result, Suv39h1-defective
      CD8+ T cells show sustained survival and increased long-term memory reprogramming
      capacity. Thus, Suv39h1 plays a critical role in marking chromatin to silence
      stem/memory genes during CD8+ T effector terminal differentiation.

PMID- 29326267
TI  - Coherent band excitations in CePd3: A comparison of neutron scattering and ab
      initio theory.
AB  - In common with many strongly correlated electron systems, intermediate valence
      compounds are believed to display a crossover from a high-temperature regime of
      incoherently fluctuating local moments to a low-temperature regime of coherent
      hybridized bands. We show that inelastic neutron scattering measurements of the
      dynamic magnetic susceptibility of CePd3 provides a benchmark for ab initio
      calculations based on dynamical mean field theory. The magnetic response is
      strongly momentum dependent thanks to the formation of coherent f-electron bands
      at low temperature, with an amplitude that is strongly enhanced by local particle
      hole interactions. The agreement between experiment and theory shows that we have
      a robust first-principles understanding of the temperature dependence of f
      electron coherence.

PMID- 29326270
TI  - Detection of the aromatic molecule benzonitrile (c-C6H5CN) in the interstellar
      medium.
AB  - Polycyclic aromatic hydrocarbons and polycyclic aromatic nitrogen heterocycles
      are thought to be widespread throughout the universe, because these classes of
      molecules are probably responsible for the unidentified infrared bands, a set of
      emission features seen in numerous Galactic and extragalactic sources. Despite
      their expected ubiquity, astronomical identification of specific aromatic
      molecules has proven elusive. We present the discovery of benzonitrile (c
      C6H5CN), one of the simplest nitrogen-bearing aromatic molecules, in the
      interstellar medium. We observed hyperfine-resolved transitions of benzonitrile
      in emission from the molecular cloud TMC-1. Simple aromatic molecules such as
      benzonitrile may be precursors for polycyclic aromatic hydrocarbon formation,
      providing a chemical link to the carriers of the unidentified infrared bands.

PMID- 29326271
TI  - Ordered macro-microporous metal-organic framework single crystals.
AB  - We constructed highly oriented and ordered macropores within metal-organic
      framework (MOF) single crystals, opening up the area of three-dimensional-ordered
      macro-microporous materials (that is, materials containing both macro- and
      micropores) in single-crystalline form. Our methodology relies on the strong
      shaping effects of a polystyrene nanosphere monolith template and a double
      solvent-induced heterogeneous nucleation approach. This process synergistically
      enabled the in situ growth of MOFs within ordered voids, rendering a single
      crystal with oriented and ordered macro-microporous structure. The improved mass
      diffusion properties of such hierarchical frameworks, together with their robust
      single-crystalline nature, endow them with superior catalytic activity and
      recyclability for bulky-molecule reactions, as compared with conventional,
      polycrystalline hollow, and disordered macroporous ZIF-8.

PMID- 29326269
TI  - Exposed subsurface ice sheets in the Martian mid-latitudes.
AB  - Thick deposits cover broad regions of the Martian mid-latitudes with a smooth
      mantle; erosion in these regions creates scarps that expose the internal
      structure of the mantle. We investigated eight of these locations and found that
      they expose deposits of water ice that can be >100 meters thick, extending
      downward from depths as shallow as 1 to 2 meters below the surface. The scarps
      are actively retreating because of sublimation of the exposed water ice. The ice
      deposits likely originated as snowfall during Mars' high-obliquity periods and
      have now compacted into massive, fractured, and layered ice. We expect the
      vertical structure of Martian ice-rich deposits to preserve a record of ice
      deposition and past climate.

PMID- 29326272
TI  - Antagonism toward the intestinal microbiota and its effect on Vibrio cholerae
      virulence.
AB  - The bacterial type VI secretion system (T6SS) is a nanomachine that delivers
      toxic effector proteins into target cells, killing them. In mice, we found that
      the Vibrio cholerae T6SS attacks members of the host commensal microbiota in
      vivo, facilitating the pathogen's colonization of the gut. This microbial
      antagonistic interaction drives measurable changes in the pathogenicity of V.
      cholerae through enhanced intestinal colonization, expression of bacterial
      virulence genes, and activation of host innate immune genes. Because ablation of
      mouse commensals by this enteric pathogen correlated with more severe diarrheal
      symptoms, we conclude that antagonism toward the gut microbiota could improve the
      fitness of V. cholerae as a pathogen by elevating its transmission to new
      susceptible hosts.

PMID- 29326273
TI  - Spatial representations of self and other in the hippocampus.
AB  - An animal's awareness of its location in space depends on the activity of place
      cells in the hippocampus. How the brain encodes the spatial position of others
      has not yet been identified. We investigated neuronal representations of other
      animals' locations in the dorsal CA1 region of the hippocampus with an
      observational T-maze task in which one rat was required to observe another rat's
      trajectory to successfully retrieve a reward. Information reflecting the spatial
      location of both the self and the other was jointly and discretely encoded by CA1
      pyramidal cells in the observer rat. A subset of CA1 pyramidal cells exhibited
      spatial receptive fields that were identical for the self and the other. These
      findings demonstrate that hippocampal spatial representations include dimensions
      for both self and nonself.

PMID- 29326268
TI  - Mapping the malaria parasite druggable genome by using in vitro evolution and
      chemogenomics.
AB  - Chemogenetic characterization through in vitro evolution combined with whole
      genome analysis can identify antimalarial drug targets and drug-resistance genes.
      We performed a genome analysis of 262 Plasmodium falciparum parasites resistant
      to 37 diverse compounds. We found 159 gene amplifications and 148 nonsynonymous
      changes in 83 genes associated with drug-resistance acquisition, where gene
      amplifications contributed to one-third of resistance acquisition events. Beyond
      confirming previously identified multidrug-resistance mechanisms, we discovered
      hitherto unrecognized drug target-inhibitor pairs, including thymidylate synthase
      and a benzoquinazolinone, farnesyltransferase and a pyrimidinedione, and a
      dipeptidylpeptidase and an arylurea. This exploration of the P. falciparum
      resistome and druggable genome will likely guide drug discovery and structural
      biology efforts, while also advancing our understanding of resistance mechanisms
      available to the malaria parasite.

PMID- 29326274
TI  - Social place-cells in the bat hippocampus.
AB  - Social animals have to know the spatial positions of conspecifics. However, it is
      unknown how the position of others is represented in the brain. We designed a
      spatial observational-learning task, in which an observer bat mimicked a
      demonstrator bat while we recorded hippocampal dorsal-CA1 neurons from the
      observer bat. A neuronal subpopulation represented the position of the other bat,
      in allocentric coordinates. About half of these "social place-cells" represented
      also the observer's own position-that is, were place cells. The representation of
      the demonstrator bat did not reflect self-movement or trajectory planning by the
      observer. Some neurons represented also the position of inanimate moving objects;
      however, their representation differed from the representation of the
      demonstrator bat. This suggests a role for hippocampal CA1 neurons in social
      spatial cognition.

PMID- 29326276
TI  - My second life as a teacher.

PMID- 29326277
TI  - ?Patiromer for the management of hyperkalaemia.
AB  - Hyperkalaemia is a potentially life-threatening condition, in which there is an
      abnormally high concentration of potassium ions in the blood.1,2 Cation-exchange
      resins (e.g. calcium or sodium polystyrene sulfonate) that bind potassium in the
      gastrointestinal tract to increase faecal elimination have been used as part of
      the management of hyperkalaemia but they have some serious adverse effects,
      including potentially fatal gastrointestinal necrosis.3,4 Patiromer (?Veltassa -
      Vifor Fresenius) is a cation-exchange polymer that is licensed for the treatment
      of hyperkalaemia in adults and, unlike other exchange resins, its licence is not
      restricted to people with anuria, severe oliguria or those requiring or
      undergoing dialysis.5,6 Here, we review the evidence for the efficacy and safety
      of patiromer and consider its place in the management of hyperkalaemia.

PMID- 29326278
TI  - An update on the management of gout.
AB  - Gout is the most common form of inflammatory arthritis and its incidence in the
      UK has steadily increased from 1.5% in 1997 to 2.5% in 2012.1,2 It is
      characterised by deposition of monosodium urate crystals in joints and tissues
      and usually presents with intermittent painful attacks followed by long periods
      of remission.3 It has been suggested that the management of gout in the UK
      remains suboptimal.1 In 2004, we concluded that there was a woeful lack of
      evidence to guide treatment or prophylaxis for gout, particularly with regard to
      choice of drug or doses.4 The introduction of new drugs and new evidence on the
      efficacy and safety of treatment options has led the European League Against
      Rheumatism (EULAR) and the British Society of Rheumatology (BSR) to update their
      guidelines on the management of gout.2,5 Nevertheless, there are differing views
      on target serum uric acid (SUA) levels and the role of urate lowering treatment
      (ULT).2,5-7 Here, we review the latest guidance on the management of gout and
      consider the role of long-term ULT.

PMID- 29326279
TI  - Gut microbiota in cardiovascular disease and heart failure.
AB  - Accumulating evidence supports a relationship between the complexity and
      diversity of the gut microbiota and host diseases. In addition to alterations in
      the gut microbial composition, the metabolic potential of gut microbiota has been
      identified as a contributing factor in the development of diseases. Recent
      technological developments of molecular and biochemical analyses enable us to
      detect and characterize the gut microbiota via assessment and classification of
      its genomes and corresponding metabolites. These advances have provided emerging
      data supporting the role of gut microbiota in various physiological activities
      including host metabolism, neurological development, energy homeostasis, and
      immune regulation. Although few human studies have looked into the causative
      associations and underlying pathophysiology of the gut microbiota and host
      disease, a growing body of preclinical and clinical evidence supports the theory
      that the gut microbiota and its metabolites have the potential to be a novel
      therapeutic and preventative target for cardiovascular and metabolic diseases. In
      this review, we highlight the interplay between the gut microbiota and its
      metabolites, and the development and progression of hypertension, heart failure,
      and chronic kidney disease.

PMID- 29326280
TI  - Autoantibodies against angiotensin and adrenergic receptors: more than a
      biomarker?
AB  - Agonistic autoantibodies (AAs) directed against receptors of the sympathetic
      nervous system and the renin-angiotensin system have been suggested to contribute
      to cardiovascular and renal disease, in particular hypertension, preeclampsia,
      and graft failure in kidney transplantation patients. Consequently, they are now
      also being studied as biomarker for these conditions. This commentary summarizes
      our current understanding of these AAs, critically discussing whether they truly
      act as agonist, and focusing on the wide array of assays that are currently used
      for their quantification.

PMID- 29326275
TI  - CX3CR1+ mononuclear phagocytes control immunity to intestinal fungi.
AB  - Intestinal fungi are an important component of the microbiota, and recent studies
      have unveiled their potential in modulating host immune homeostasis and
      inflammatory disease. Nonetheless, the mechanisms governing immunity to gut
      fungal communities (mycobiota) remain unknown. We identified CX3CR1+ mononuclear
      phagocytes (MNPs) as being essential for the initiation of innate and adaptive
      immune responses to intestinal fungi. CX3CR1+ MNPs express antifungal receptors
      and activate antifungal responses in a Syk-dependent manner. Genetic ablation of
      CX3CR1+ MNPs in mice led to changes in gut fungal communities and to severe
      colitis that was rescued by antifungal treatment. In Crohn's disease patients, a
      missense mutation in the gene encoding CX3CR1 was identified and found to be
      associated with impaired antifungal responses. These results unravel a role of
      CX3CR1+ MNPs in mediating interactions between intestinal mycobiota and host
      immunity at steady state and during inflammatory disease.

PMID- 29326281
TI  - Evaluation of Overall Response Rate and Progression-Free Survival as Potential
      Surrogate Endpoints for Overall Survival in Immunotherapy Trials.
AB  - Purpose: With the approval of immunotherapies for a variety of indications,
      methods to assess treatment benefit addressing the response patterns observed are
      important. We evaluated RECIST criteria-based overall response rate (ORR) and
      progression-free survival (PFS) as potential surrogate endpoints of overall
      survival (OS), and explored a modified definition of PFS by altering the
      threshold percentage determining disease progression to assess the association
      with survival benefit in immunotherapy trials.Experimental Design: Thirteen
      randomized, multicenter, active-control trials containing immunotherapeutic
      agents submitted to the FDA were analyzed. Associations between treatment effects
      of ORR, PFS, modified PFS, and OS were evaluated at individual and trial levels.
      Patient-level responder analysis was performed for PFS and OS.Results: The
      coefficient of determination (R2) measured the strength of associations, where
      values near 1 imply surrogacy and values close to 0 suggest no association. At
      the trial level, the association between hazard ratios (HR) of PFS and OS was R2
      = 0.1303, and between the odds ratio (OR) of ORR and HR of OS was R2 = 0.1277. At
      the individual level, the Spearman rank correlation coefficient between PFS and
      OS was 0.61. Trial-level associations between modified PFS and OS ranged between
      0.07 and 0.1, and individual-level correlations were approximately 0.6. HRs of
      PFS and OS for responders versus nonresponders were 0.129 [95% confidence
      interval (CI), 0.11-0.15] and 0.118 (95% CI, 0.11-0.13),
      respectively.Conclusions: Although responders exhibited longer survival and PFS
      than nonresponders, the trial-level and individual-level associations were weak
      between PFS/ORR and OS. Modifications to PFS did not improve associations. Clin
      Cancer Res; 24(10); 2268-75. (c)2018 AACRSee related commentary by Korn and
      Freidlin, p. 2239.

PMID- 29326283
TI  - Rash on extensor surfaces of a child.

PMID- 29326284
TI  - Trust may reduce or delay chemotherapy because of staff shortages.

PMID- 29326282
TI  - RNF126 as a Biomarker of a Poor Prognosis in Invasive Breast Cancer and CHEK1
      Inhibitor Efficacy in Breast Cancer Cells.
AB  - Purpose: (i) To investigate the expression of the E3 ligase, RNF126, in human
      invasive breast cancer and its links with breast cancer outcomes; and (ii) to
      test the hypothesis that RNF126 determines the efficacy of inhibitors targeting
      the cell-cycle checkpoint kinase, CHEK1.Experimental Design: A retrospective
      analysis by immunohistochemistry (IHC) compared RNF126 staining in 110 invasive
      breast cancer and 78 paired adjacent normal tissues with clinicopathologic data.
      Whether RNF126 controls CHEK1 expression was determined by chromatin
      immunoprecipitation and a CHEK1 promoter driven luciferase reporter. Staining for
      these two proteins by IHC using tissue microarrays was also conducted. Cell
      killing/replication stress induced by CHEK1 inhibition was evaluated in cells,
      with or without RNF126 knockdown, by MTT/colony formation, replication stress
      biomarker immunostaining and DNA fiber assays.Results: RNF126 protein expression
      was elevated in breast cancer tissue samples. RNF126 was associated with a poor
      clinical outcome after multivariate analysis and was an independent predictor.
      RNF126 promotes CHEK1 transcript expression. Critically, a strong correlation
      between RNF126 and CHEK1 proteins was identified in breast cancer tissue and cell
      lines. The inhibition of CHEK1 induced a greater cell killing and a higher level
      of replication stress in breast cancer cells expressing RNF126 compared to RNF126
      depleted cells.Conclusions: RNF126 protein is highly expressed in invasive breast
      cancer tissue. The high expression of RNF126 is an independent predictor of a
      poor prognosis in invasive breast cancer and is considered a potential biomarker
      of a cancer's responsiveness to CHEK1 inhibitors. CHEK1 inhibition targets breast
      cancer cells expressing higher levels of RNF126 by enhancing replication stress.
      Clin Cancer Res; 24(7); 1629-43. (c)2018 AACR.

PMID- 29326286
TI  - Correction: Dimethyl fumarate for psoriasis.

PMID- 29326287
TI  - The apical scaffold big bang binds to spectrins and regulates the growth of
      Drosophila melanogaster wing discs.
AB  - During development, cell numbers are tightly regulated, ensuring that tissues and
      organs reach their correct size and shape. Recent evidence has highlighted the
      intricate connections between the cytoskeleton and the regulation of the key
      growth control Hippo pathway. Looking for apical scaffolds regulating tissue
      growth, we describe that Drosophila melanogaster big bang (Bbg), a poorly
      characterized multi-PDZ scaffold, controls epithelial tissue growth without
      affecting epithelial polarity and architecture. bbg-mutant tissues are smaller,
      with fewer cells that are less apically constricted than normal. We show that Bbg
      binds to and colocalizes tightly with the beta-heavy-Spectrin/Kst subunit at the
      apical cortex and promotes Yki activity, F-actin enrichment, and the
      phosphorylation of the myosin II regulatory light chain Spaghetti squash. We
      propose a model in which the spectrin cytoskeleton recruits Bbg to the cortex,
      where Bbg promotes actomyosin contractility to regulate epithelial tissue growth.

PMID- 29326289
TI  - Prevalence of hippocampal enlarged perivascular spaces in a sample of patients
      with hypertension and their relation with vascular risk factors and cognitive
      function.
AB  - OBJECTIVES: The clinical importance of hippocampal enlarged perivascular spaces
      (H-EPVS) remains uncertain. We aimed to study their association with vascular
      risk factors, cognitive function and mild cognitive impairment (MCI). METHODS:
      Data were obtained from the ISSYS (Investigating Silent Strokes in hYpertensives,
      a magnetic resonance imaging Study) cohort, which is a prospective study of
      patients with hypertension aged 50-70 with no prior stroke or dementia.
      Participants were clinically evaluated and underwent a cognitive screening test,
      Dementia Rating Scale-2, which includes five cognitive subscales (attention,
      initiation/perseveration, conceptualisation, construction and memory). Besides,
      they were diagnosed with MCI or normal ageing following standard criteria. H-EPVS
      were manually counted on brain MRI according to a previous scale and defined as
      extensive when H-EPVS count was >=7 (upper quartile). Multivariate models were
      created to study the relationship between H-EPVS, vascular risk factors and
      cognitive function. RESULTS: 723 patients were included; the median age was 64
      (59-67) and 51% were male. Seventy-two patients (10%) were diagnosed with MCI and
      612 (84.6%) had at least 1 H-EPVS. Older age (OR per year=1.04, 95% CI 1.01 to
      1.08) and poor blood pressure treatment compliance (OR=1.50, 95% CI 1.07 to 2.11)
      were independently associated with extensive H-EPVS. Regarding cognitive
      function, H-EPVS were independently and inversely correlated with verbal
      reasoning (beta=-0.021, 95% CI -0.038 to -0.003). No association was found
      between H-EPVS and MCI. CONCLUSIONS: H-EPVS are a frequent finding in patients
      with hypertension and are associated with ageing and poor hypertension treatment
      compliance. Besides, H-EPVS are associated with worse verbal reasoning function.

PMID- 29326288
TI  - Drosophila Big bang regulates the apical cytocortex and wing growth through
      junctional tension.
AB  - Growth of epithelial tissues is regulated by a plethora of components, including
      signaling and scaffolding proteins, but also by junctional tension, mediated by
      the actomyosin cytoskeleton. However, how these players are spatially organized
      and functionally coordinated is not well understood. Here, we identify the
      Drosophila melanogaster scaffolding protein Big bang as a novel regulator of
      growth in epithelial cells of the wing disc by ensuring proper junctional
      tension. Loss of big bang results in the reduction of the regulatory light chain
      of nonmuscle myosin, Spaghetti squash. This is associated with an increased
      apical cell surface, decreased junctional tension, and smaller wings. Strikingly,
      these phenotypic traits of big bang mutant discs can be rescued by expressing
      constitutively active Spaghetti squash. Big bang colocalizes with Spaghetti
      squash in the apical cytocortex and is found in the same protein complex. These
      results suggest that in epithelial cells of developing wings, the scaffolding
      protein Big bang controls apical cytocortex organization, which is important for
      regulating cell shape and tissue growth.

PMID- 29326290
TI  - Functional lesional neurosurgery for tremor: a systematic review and meta
      analysis.
AB  - BACKGROUND: This work evaluates the consistency, effect size and incidence of
      persistent side effects of lesional neurosurgical interventions in the treatment
      of tremor due to Parkinson's disease (PD), essential tremor (ET), multiple
      sclerosis (MS) and midbrain lesions. METHODS: Systematic review and meta-analysis
      according to PRISMA-P guidelines. Random effects meta-analysis of standardised
      mean difference based on a peer-reviewed protocol (PROSPERO no. CRD42016048049).
      RESULTS: From 1249 abstracts screened, 86 peer-reviewed studies reporting 102
      cohorts homogeneous for tremor aetiology, surgical target and technique were
      included.Effect on PD tremor was better when targeted at the ventral intermediate
      nucleus (V.im.) by radiofrequency ablation (RF) (Hedge's g: -4.15;) over V.im. by
      Gamma Knife (GK) (-2.2), subthalamic nucleus (STN) by RF (-1.12) and globus
      pallidus internus (GPi) by RF (-0.89). For ET MRI-guided focused ultrasound
      (MRIgFUS) ablation of the cerebellothalamic tract (CTT) (-2.35) and V.im. (-2.08)
      showed similar mean tremor reductions to V.im. ablation by RF (-2.42) or GK (
      2.13). In MS V.im. ablation by GK (-1.96) and RF (-1.63) were similarly
      effective.Mean rates of persistent side effects after unilateral lesions in PD
      were 12.8% (RF V.im.), 13.6% (RF STN), 9.2% (RF GPi), 0.7% (GK V.im.) and 7.0%
      (MRIgFUS V.im.). For ET, rates were 9.3% (RF V.im.), 1.8% (GK V.im.), 18.7%
      (MRIgFUS V.im.) and 0.0% (MRIgFUS CTT), for MS 37.7% (RF V.im.) and for rubral
      tremor 30.3% (RF V.im.). CONCLUSION: This meta-analysis quantifies safety,
      consistency and efficacy of lesional neurosurgical interventions for tremor by
      target, technique and aetiology.

PMID- 29326291
TI  - Anterior hippocampal grey matter predicts mental health outcome in functional
      neurological disorders: an exploratory pilot study.

PMID- 29326292
TI  - Nationwide epidemiological study of neuromyelitis optica in Japan.

PMID- 29326293
TI  - Physiological effects of subthalamic nucleus deep brain stimulation surgery in
      cervical dystonia.
AB  - BACKGROUND: Subthalamic nucleus deep brain stimulation (STN DBS) surgery is
      clinically effective for treatment of cervical dystonia; however, the underlying
      physiology has not been examined. We used transcranial magnetic stimulation (TMS)
      to examine the effects of STN DBS on sensorimotor integration, sensorimotor
      plasticity and motor cortex excitability, which are identified as the key
      pathophysiological features underlying dystonia. METHODS: TMS paradigms of short
      latency afferent inhibition (SAI) and long latency afferent inhibition (LAI) were
      used to examine the sensorimotor integration. Sensorimotor plasticity was
      measured with paired associative stimulation paradigm, and motor cortex
      excitability was examined with short interval intracortical inhibition and
      intracortical facilitation. DBS was turned off and on to record these measures.
      RESULTS: STN DBS modulated SAI and LAI, which correlated well with the acute
      clinical improvement. While there were no changes seen in the motor cortex
      excitability, DBS was found to normalise the sensorimotor plasticity; however,
      there was no clinical correlation. CONCLUSION: Modulation of sensorimotor
      integration is a key contributor to clinical improvement with acute stimulation
      of STN. Since the motor cortex excitability did not change and the change in
      sensorimotor plasticity did not correlate with clinical improvement, STN DBS
      demonstrates restricted effects on the underlying physiology. CLINICAL TRIAL
      REGISTRATION: NCT01671527.

PMID- 29326294
TI  - Guillain-Barre syndrome in southern China: retrospective analysis of hospitalised
      patients from 14 provinces in the area south of the Huaihe River.
AB  - OBJECTIVES: The clinical and epidemiological profiles of Guillain-Barre syndrome
      (GBS) in southern China have yet to be fully recognised. We aimed to investigate
      the subtypes of GBS in southern China, compare the clinical features of
      demyelinating form with that of axonal form and test whether preceding infections
      and age have influence on the clinical phenotype, disease course and severity of
      GBS. METHODS: Medical records of patients with a diagnosis of GBS admitted to 31
      tertiary hospitals, located in 14 provinces in southern China, from 1 January
      2013 to 30 September 2016, were collected and retrospectively reviewed. RESULTS:
      Finally. 1056 patients, including 887 classic GBS and 169 variants, were
      enrolled. The 661 classic patients with available electromyographic data were
      grouped as having acute inflammatory demyelinating polyneuropathy (AIDP, 49.0%),
      acute motor axonal neuropathy (AMAN, 18.8%), inexcitable (0.9%) and equivocal
      (31.3%). In contrast to AIDP, patients with AMAN were characterised by earlier
      nadir (P=0.000), higher Hughes score at nadir (P=0.003) and at discharge
      (P=0.000). Preceding upper respiratory infections were identified in 369 (34.9%)
      patients, who were more inclined to develop AIDP (P=0.000) and Miller-Fisher
      syndrome (P=0.027), whereas gastrointestinal infection were found in 89 (8.4%)
      patients, who were more prone to develop AMAN (P=0.000), with more severe illness
      (P=0.001) and longer hospital stay (P=0.009). Children (<=15 years) and the
      elderly (>=56 years) were more severe at nadir, the elderly had the longest
      hospital stay (P=0.023). CONCLUSION: AIDP is the predominant form in southern
      China, which is different from data of northern China. The different subtypes,
      preceding infection and age of onset can partially determine the disease
      progression, severity and short-term recovery speed of GBS. CLINICAL TRIAL
      REGISTRATION: ChiCTR-RRC-17014152.

PMID- 29326295
TI  - Randomised controlled trial of escitalopram for cervical dystonia with dystonic
      jerks/tremor.
AB  - OBJECTIVE: Trials for additional or alternative treatments for cervical dystonia
      (CD) are scarce since the introduction of botulinum neurotoxin (BoNT). We
      performed the first trial to investigate whether dystonic jerks/tremor in
      patients with CD respond to the selective serotonin reuptake inhibitor (SSRI)
      escitalopram. METHODS: In a randomised, double-blind, crossover trial, patients
      with CD received escitalopram and placebo for 6 weeks. Treatment with BoNT was
      continued, and scores on rating scales regarding dystonia, psychiatric symptoms
      and quality of life (QoL) were compared. Primary endpoint was the proportion of
      patients that improved at least one point on the Clinical Global Impression Scale
      for jerks/tremor scored by independent physicians with experience in movement
      disorders. RESULTS: Fifty-threepatients were included. In the escitalopram
      period, 14/49 patients (29%) improved on severity of jerks/tremor versus 11/48
      patients (23%) in the placebo period (P=0.77). There were no significant
      differences between baseline and after treatment with escitalopram or placebo on
      severity of dystonia or jerks/tremor. Psychiatric symptoms and QoL improved
      significantly in both periods compared with baseline. There were no significant
      differences between treatment with escitalopram and placebo for dystonia,
      psychiatric or QoL rating scales. During treatment with escitalopram, patients
      experienced slightly more adverse events, but no serious adverse events occurred.
      CONCLUSION: In this innovative trial, no add-on effect of escitalopram for
      treatment of CD with jerks was found on motor or psychiatric symptoms. However,
      we also did not find a reason to withhold patients treatment with SSRIs for
      depression and anxiety, which are common in dystonia. TRIAL REGISTRATION NUMBER:
      NTR2178.

PMID- 29326296
TI  - Intrathecal baclofen therapy versus conventional medical management for severe
      poststroke spasticity: results from a multicentre, randomised, controlled, open
      label trial (SISTERS).
AB  - BACKGROUND: Intrathecal baclofen (ITB) is a treatment option for patients with
      severe poststroke spasticity (PSS) who have not reached their therapy goal with
      other interventions. METHODS: 'Spasticity In Stroke-Randomised Study' (SISTERS)
      was a randomised, controlled, open-label, multicentre phase IV study to evaluate
      the efficacy and safety of ITB therapy versus conventional medical management
      (CMM) with oral antispastic medications for treatment of PSS. Patients with
      chronic stroke with spasticity in >=2 extremities and an Ashworth Scale (AS)
      score >=3 in at least two affected muscle groups in the lower extremities (LE)
      were randomised (1:1) to ITB or CMM. Both treatment arms received physiotherapy
      throughout. The primary outcome was the change in the average AS score in the LE
      of the affected body side from baseline to month 6. Analyses were performed for
      all patients as randomised (primary analysis) and all randomised patients as
      treated (safety analysis). RESULTS: Of 60 patients randomised to ITB (n=31) or
      CMM (n=29), 48 patients (24 per arm) completed the study. The primary analysis
      showed a significant effect of ITB therapy over CMM (mean AS score reduction, 
      0.99 (ITB) vs -0.43 (CMM); Hodges-Lehmann estimate, -0.667(95.1%CI -1.0000 to 
      0.1667); P=0.0140). More patients reported adverse events while receiving ITB
      (24/25 patients, 96%; 149 events) compared with CMM (22/35, 63%; 77 events),
      although events were generally consistent with the known safety profile of ITB
      therapy. CONCLUSIONS: These data support the use of ITB therapy as an alternative
      to CMM for treatment of generalised PSS in adults. TRIAL REGISTRATION NUMBER:
      NCT01032239; Results.

PMID- 29326297
TI  - Current status and future directions of Levy walk research.
AB  - Levy walks are a mathematical construction useful for describing random patterns
      of movement with bizarre fractal properties that seem to have no place in
      biology. Nonetheless, movement patterns resembling Levy walks have been observed
      at scales ranging from the microscopic to the ecological. They have been seen in
      the molecular machinery operating within cells during intracellular trafficking,
      in the movement patterns of T cells within the brain, in DNA, in some molluscs,
      insects, fish, birds and mammals, in the airborne flights of spores and seeds,
      and in the collective movements of some animal groups. Levy walks are also
      evident in trace fossils (ichnofossils) - the preserved form of tracks made by
      organisms that occupied ancient sea beds about 252-66 million years ago. And they
      are utilised by algae that originated around two billion years ago, and still
      exist today. In September of 2017, leading researchers from across the life
      sciences, along with mathematicians and physicists, got together at a Company of
      Biologists' Workshop to discuss the origins and biological significance of these
      movement patterns. In this Review the essence of the technical and sometimes
      heated discussions is distilled and made accessible for all. In just a few pages,
      the reader is taken from a gentle introduction to the frontiers of a very active
      field of scientific enquiry. What emerges is a fascinating story of a truly inter
      disciplinary scientific endeavour that is seeking to better understand movement
      patterns occurring across all biological scales.

PMID- 29326298
TI  - Smoking duration alone provides stronger risk estimates of chronic obstructive
      pulmonary disease than pack-years.
AB  - BACKGROUND: Cigarette smoking is the strongest risk factor for COPD. Smoking
      burden is frequently measured in pack-years, but the relative contribution of
      cigarettes smoked per day versus duration towards the development of structural
      lung disease, airflow obstruction and functional outcomes is not known. METHODS:
      We analysed cross-sectional data from a large multicentre cohort (COPDGene) of
      current and former smokers. Primary outcome was airflow obstruction (FEV1/FVC);
      secondary outcomes included five additional measures of disease: FEV1, CT
      emphysema, CT gas trapping, functional capacity (6 min walk distance, 6MWD) and
      respiratory morbidity (St George's Respiratory Questionnaire, SGRQ). Generalised
      linear models were estimated to compare the relative contribution of each smoking
      variable with the outcomes, after adjustment for age, race, sex, body mass index,
      CT scanner, centre, age of smoking onset and current smoking status. We also
      estimated adjusted means of each outcome by categories of pack-years and combined
      groups of categorised smoking duration and cigarettes/day, and estimated linear
      trends of adjusted means for each outcome by categorised cigarettes/day, smoking
      duration and pack-years. RESULTS: 10 187 subjects were included. For FEV1/FVC,
      standardised beta coefficient for smoking duration was greater than for
      cigarettes/day and pack-years (P<0.001). After categorisation, there was a linear
      increase in adjusted means FEV1/FVC with increase in pack-years (regression
      coefficient beta=-0.023+/-SE0.003; P=0.003) and duration over all ranges of
      smoking cigarettes/day (beta=-0.041+/-0.004; P<0.001) but a relatively flat slope
      for cigarettes/day across all ranges of smoking duration (beta=-0.009+/-0.0.009;
      P=0.34). Strength of association of duration was similarly greater than pack
      years for emphysema, gas trapping, FEV1, 6MWD and SGRQ. CONCLUSION: Smoking
      duration alone provides stronger risk estimates of COPD than the composite index
      of pack-years. TRIAL REGISTRATION NUMBER: Post-results; NCT00608764.

PMID- 29326299
TI  - Targeting mutant KRAS with CRISPR-Cas9 controls tumor growth.
AB  - KRAS is the most frequently mutated oncogene in human tumors, and its activating
      mutations represent important therapeutic targets. The combination of Cas9 and
      guide RNA from the CRISPR-Cas system recognizes a specific DNA sequence and makes
      a double-strand break, which enables editing of the relevant genes. Here, we
      harnessed CRISPR to specifically target mutant KRAS alleles in cancer cells. We
      screened guide RNAs using a reporter system and validated them in cancer cells
      after lentiviral delivery of Cas9 and guide RNA. The survival, proliferation, and
      tumorigenicity of cancer cells in vitro and the growth of tumors in vivo were
      determined after delivery of Cas9 and guide RNA. We identified guide RNAs that
      efficiently target mutant KRAS without significant alterations of the wild-type
      allele. Doxycycline-inducible expression of this guide RNA in KRAS-mutant cancer
      cells transduced with a lentiviral vector encoding Cas9 disrupted the mutant KRAS
      gene, leading to inhibition of cancer cell proliferation both in vitro and in
      vivo. Intra-tumoral injection of lentivirus and adeno-associated virus expressing
      Cas9 and sgRNA suppressed tumor growth in vivo, albeit incompletely, in
      immunodeficient mice. Expression of Cas9 and the guide RNA in cells containing
      wild-type KRAS did not alter cell survival or proliferation either in vitro and
      in vivo. Our study provides a proof-of-concept that CRISPR can be utilized to
      target driver mutations of cancers in vitro and in vivo.

PMID- 29326301
TI  - Prognostic roles of signal transducers activators of transcription family in
      human breast cancer.
AB  - Signal transducer and activator of transcription (STAT) family are critical
      transcription factors, which have been proved as prognostic predictors for a
      number of cancers. However, the prognostic roles of STAT family in breast cancer
      patients remain in dispute. In this study, we mined the 'Kaplan-Meier plotter'
      (KM plotter) online database to explore the prognostic roles of STAT family mRNA
      expression in breast cancer including overall survival (OS), progression-free
      survival (PFS), as well as post-progression survival (PPS). The results suggest
      high mRNA expression of all the individual STATs, except STAT1 and STAT2, are
      significantly associated with favorable OS in breast cancer patients; high STAT1
      mRNA expression is significantly associated with worse RFS and all the other
      individual STATs, except STAT3, are significantly associated with better RFS in
      breast cancer patients; only high STAT5b mRNA expression is significantly related
      to better PPS in breast cancer patients. Additionally, we explored the prognostic
      values of individual STATs in other clinicopathological features, such as
      pathological grades, estrogen receptor (ER) status and so on. The results
      suggest, except STAT2 and STAT6, high mRNA expression of STATs is related to a
      favorable prognosis especially for high pathological grade; high STAT5 mRNA
      expression indicates a favorable prognosis no matter under ER positive or
      negative status; high STAT4 mRNA expression suggests a favorable prognosis under
      HER2 negative status. Our results indicate that individual STATs, except STAT1
      and STAT2, may act as a favorable prognostic biomarker in breast cancer.
      Nevertheless, further investigations on a larger population are warranted.

PMID- 29326300
TI  - Relationship between histone modifications and transcription factor binding is
      protein family specific.
AB  - The very small fraction of putative binding sites (BSs) that are occupied by
      transcription factors (TFs) in vivo can be highly variable across different cell
      types. This observation has been partly attributed to changes in chromatin
      accessibility and histone modification (HM) patterns surrounding BSs. Previous
      studies focusing on BSs within DNA regulatory regions found correlations between
      HM patterns and TF binding specificities. However, a mechanistic understanding of
      TF-DNA binding specificity determinants is still not available. The ability to
      predict in vivo TF binding on a genome-wide scale requires the identification of
      features that determine TF binding based on evolutionary relationships of DNA
      binding proteins. To reveal protein family-dependent mechanisms of TF binding, we
      conducted comprehensive comparisons of HM patterns surrounding BSs and non-BSs
      with exactly matched core motifs for TFs in three cell lines: 33 TFs in GM12878,
      37 TFs in K562, and 18 TFs in H1-hESC. These TFs displayed protein family
      specific preferences for HM patterns surrounding BSs, with high agreement among
      cell lines. Moreover, compared to models based on DNA sequence and shape at
      flanking regions of BSs, HM-augmented quantitative machine-learning methods
      resulted in increased performance in a TF family-specific manner. Analysis of the
      relative importance of features in these models indicated that TFs, displaying
      larger HM pattern differences between BSs and non-BSs, bound DNA in an HM
      specific manner on a protein family-specific basis. We propose that TF family
      specific HM preferences reveal distinct mechanisms that assist in guiding TFs to
      their cognate BSs by altering chromatin structure and accessibility.

PMID- 29326303
TI  - Authors' reply to Sharvill and Beales.

PMID- 29326304
TI  - Gastrointestinal protection with dual antiplatelet therapies.

PMID- 29326302
TI  - Role of ClC-K and barttin in low potassium-induced sodium chloride cotransporter
      activation and hypertension in mouse kidney.
AB  - The sodium chloride cotransporter (NCC) has been identified as a key molecule
      regulating potassium balance. The mechanisms of NCC regulation during low
      extracellular potassium concentrations have been studied in vitro. These studies
      have shown that hyperpolarization increased chloride efflux, leading to the
      activation of chloride-sensitive with-no-lysine kinase (WNK) kinases and their
      downstream molecules, including STE20/SPS1-related proline/alanine-rich kinase
      (SPAK) and NCC. However, this mechanism was not studied in vivo Previously, we
      developed the barttin hypomorphic mouse (Bsndneo/neo mice), expressing very low
      levels of barttin and ClC-K channels, because barttin is an essential beta
      subunit of ClC-K. In contrast with Bsnd-/- mice, Bsndneo/neo mice survived to
      adulthood. In Bsndneo/neo mice, SPAK and NCC activation after consuming a low
      potassium diet was clearly impaired compared with that in wild-type (WT) mice. In
      ex vivo kidney slice experiment, the increase in pNCC and SPAK in low-potassium
      medium was also impaired in Bsndneo/neo mice. Furthermore, increased blood
      pressure was observed in WT mice fed a high-salt and low-potassium diet, which
      was not evident in Bsndneo/neo mice. Thus, our study provides in vivo evidence
      that, in response to a low-potassium diet, ClC-K and barttin play important roles
      in the activation of the WNK4-SPAK-NCC cascade and blood pressure regulation.

PMID- 29326305
TI  - Evaluation and Management of CKD in the Nonkidney Solid Organ Transplant
      Recipient.

PMID- 29326306
TI  - Weekly Standard Kt/Vurea and Clinical Outcomes in Home and In-Center
      Hemodialysis.
AB  - BACKGROUND AND OBJECTIVES: Patients undergoing hemodialysis with a frequency
      other than thrice weekly are not included in current clinical performance metrics
      for dialysis adequacy. The weekly standard Kt/Vurea incorporates treatment
      frequency, but there are limited data on its association with clinical outcomes.
      DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We used multivariable regression
      to examine the association of dialysis standard Kt/Vurea with BP and metabolic
      control (serum potassium, calcium, bicarbonate, and phosphorus) in patients
      incidental to dialysis treated with home (n=2373) or in-center hemodialysis
      (n=109,273). We further used Cox survival models to examine the association of
      dialysis standard Kt/Vurea with mortality, hospitalization, and among patients on
      home hemodialysis, transfer to in-center hemodialysis. RESULTS: After adjustment
      for potential confounders, patients with dialysis standard Kt/Vurea <2.1 had
      higher BPs compared with patients with standard Kt/Vurea 2.1 to <2.3 (3.4 mm Hg
      higher [P<0.001] for home hemodialysis and 0.9 mm Hg higher [P<0.001] for in
      center hemodialysis). There were no clinically meaningful associations between
      dialysis standard Kt/Vurea and markers of metabolic control, irrespective of
      dialysis modality. There was no association between dialysis standard Kt/Vurea
      and risk for mortality, hospitalization, or transfer to in-center hemodialysis
      among patients undergoing home hemodialysis. Among patients on in-center
      hemodialysis, dialysis standard Kt/Vurea <2.1 was associated with higher risk
      (adjusted hazard ratio, 1.11; 95% confidence interval, 1.07 to 1.14) and standard
      Kt/Vurea >=2.3 was associated with lower risk (adjusted hazard ratio, 0.97; 95%
      confidence interval, 0.94 to 0.99) for death compared with standard Kt/Vurea 2.1
      to <2.3. Additional analyses limited to patients with available data on residual
      kidney function showed similar relationships of dialysis and total (dialysis plus
      kidney) standard Kt/Vurea with outcomes. CONCLUSIONS: Current targets for
      standard Kt/Vurea have limited utility in identifying individuals at increased
      risk for adverse clinical outcomes for those undergoing home hemodialysis but may
      enhance risk stratification for in-center hemodialysis.

PMID- 29326308
TI  - Addressing Physician Burnout: Nephrologists, How Safe Are We?

PMID- 29326307
TI  - Mycophenolate Mofetil in Combination with Steroids for Treatment of C3
      Glomerulopathy: A Case Series.
AB  - BACKGROUND AND OBJECTIVES: C3 glomerulopathy is a form of complement-mediated GN.
      Immunosuppressive therapy may be beneficial in the treatment of C3
      glomerulopathy. Mycophenolate mofetil is an attractive treatment option given its
      role in the treatment of other complement-mediated diseases and the results of
      the Spanish Group for the Study of Glomerular Diseases C3 Study. Here, we study
      the outcomes of patients with C3 glomerulopathy treated with steroids and
      mycophenolate mofetil. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We
      conducted a retrospective chart review of patients in the C3 glomerulopathy
      registry at Columbia University and identified patients treated with
      mycophenolate mofetil for at least 3 months and follow-up for at least 1 year. We
      studied clinical, histologic, and genetic data for the whole group and compared
      data for those who achieved complete or partial remission (responders) with those
      who did not achieve remission (nonresponders). We compared remission with
      mycophenolate mofetil with remission with other immunosuppressive regimens.
      RESULTS: We identified 30 patients who met inclusion criteria. Median age was 25
      years old (interquartile range, 18-36), median creatinine was 1.07 mg/dl
      (interquartile range, 0.79-1.69), and median proteinuria was 3200 mg/g creatinine
      (interquartile range, 1720-6759). The median follow-up time was 32 months
      (interquartile range, 21-68). Twenty (67%) patients were classified as
      responders. There were no significant differences in baseline characteristics
      between responders and nonresponders, although initial proteinuria was lower
      (median 2468 mg/g creatinine) in responders compared with nonresponders (median
      5000 mg/g creatinine) and soluble membrane attack complex levels were higher in
      responders compared with nonresponders. For those tapered off mycophenolate
      mofetil, relapse rate was 50%. Genome-wide analysis on complement genes was done,
      and in 12 patients, we found 18 variants predicted to be damaging. None of these
      variants were previously reported to be pathogenic. Mycophenolate mofetil with
      steroids outperformed other immunosuppressive regimens. CONCLUSIONS: Among
      patients who tolerated mycophenolate mofetil, combination therapy with steroids
      induced remission in 67% of this cohort. Heavier proteinuria at the start of
      therapy and lower soluble membrane attack complex levels were associated with
      treatment resistance.

PMID- 29326309
TI  - Nephrology at a Crossroads.

PMID- 29326310
TI  - Burnout in Nephrology: Implications on Recruitment and the Workforce.

PMID- 29326312
TI  - FOXO3a (Forkhead Transcription Factor O Subfamily Member 3a) Links Vascular
      Smooth Muscle Cell Apoptosis, Matrix Breakdown, Atherosclerosis, and Vascular
      Remodeling Through a Novel Pathway Involving MMP13 (Matrix Metalloproteinase 13).
AB  - OBJECTIVE: Vascular smooth muscle cell (VSMC) apoptosis accelerates
      atherosclerosis and promotes breakdown of the extracellular matrix, but the
      mechanistic links between these 2 processes are unknown. The forkhead protein
      FOXO3a (forkhead transcription factor O subfamily member 3a) is activated in
      human atherosclerosis and induces a range of proapoptotic and other
      transcriptional targets. We, therefore, determined the mechanisms and
      consequences of FOXO3a activation in atherosclerosis and arterial remodeling
      after injury. APPROACH AND RESULTS: Expression of a conditional FOXO3a allele
      (FOXO3aA3ER) potently induced VSMC apoptosis, expression and activation of MMP13
      (matrix metalloproteinase 13), and downregulation of endogenous TIMPs (tissue
      inhibitors of MMPs). mmp13 and mmp2 were direct FOXO3a transcriptional targets in
      VSMCs. Activation of endogenous FOXO3a also induced MMP13, extracellular matrix
      degradation, and apoptosis, and MMP13-specific inhibitors and fibronectin reduced
      FOXO3a-mediated apoptosis. FOXO3a activation in mice with VSMC-restricted
      FOXO3aA3ER induced MMP13 expression and activity and medial VSMC apoptosis.
      FOXO3a activation in FOXO3aA3ER/ApoE-/- (apolipoprotein E deficient) mice
      increased atherosclerosis, increased necrotic core and reduced fibrous cap areas,
      and induced features of medial degeneration. After carotid artery ligation,
      FOXO3a activation increased VSMC apoptosis, VSMC proliferation, and neointima
      formation, all of which were reduced by MMP13 inhibition. CONCLUSIONS: FOXO3a
      activation induces VSMC apoptosis and extracellular matrix breakdown, in part,
      because of transcriptional activation of MMP13. FOXO3a activation promotes
      atherosclerosis and medial degeneration and increases neointima after injury that
      is partly dependent on MMP13. FOXO3a-induced MMP activation represents a direct
      mechanistic link between VSMC apoptosis and matrix breakdown in vascular disease.

PMID- 29326313
TI  - DNA Methylation and Age-Independent Cardiovascular Risk, an Epigenome-Wide
      Approach: The REGICOR Study (REgistre GIroni del COR).
AB  - OBJECTIVE: The objectives of this study were to decipher whether age-independent
      cardiovascular risk is associated with DNA methylation at 5'-cytosine-phosphate
      guanine-3' (CpG) level and to determine whether these differential methylation
      signatures are associated with the incidence of cardiovascular events. APPROACH
      AND RESULTS: We designed a 2-stage, cross-sectional, epigenome-wide association
      study. Age-independent cardiovascular risk calculation was based on vascular age
      and on the residuals of the relationship between age and cardiovascular risk.
      Blood DNA methylomes from 2 independent populations were profiled using the
      Infinium HumanMethylation450 BeadChip. The discovery stage of these studies was
      performed in the REGICOR cohort (REgistre GIroni del COR; n=645). Next, we
      validated the initial findings in the Framingham Offspring Study (n=2542). Eight
      CpGs located in 4 genes (AHRR, CPT1A, PPIF, and SBNO2) and 3 intergenic regions
      showed differential methylation in association with age-independent
      cardiovascular risk (P<=1.17*10-7). These CpGs explained 12.01% to 15.16% of the
      variability of age-independent cardiovascular risk in REGICOR and 7.51% to 8.53%
      in Framingham Offspring Study. Four of them were only related to smoking, 3 were
      related to smoking and body mass index, and 1 to diabetes mellitus, triglycerides
      levels, and body mass index (P<=7.81*10-4). In addition, we developed methylation
      risk scores based on these CpGs and observed an association between these scores
      and cardiovascular disease incidence (hazard ratio=1.32; 95% confidence interval:
      1.16-1.51). CONCLUSIONS: Age-independent cardiovascular risk was related to
      different DNA methylation profiles, with 8 CpGs showing differential methylation
      patterns. Most of these CpGs were associated with smoking, and 3 of them were
      also related to body mass index. Risk scores based on these differential
      methylation patterns were associated with cardiovascular events and could be
      useful predictive indices.

PMID- 29326311
TI  - Spatial effects - site-specific regulation of actin and microtubule organization
      by septin GTPases.
AB  - The actin and microtubule cytoskeletons comprise a variety of networks with
      distinct architectures, dynamics and protein composition. A fundamental question
      in eukaryotic cell biology is how these networks are spatially and temporally
      controlled, so they are positioned in the right intracellular places at the right
      time. While significant progress has been made in understanding the self-assembly
      of actin and microtubule networks, less is known about how they are patterned and
      regulated in a site-specific manner. In mammalian systems, septins are a large
      family of GTP-binding proteins that multimerize into higher-order structures,
      which associate with distinct subsets of actin filaments and microtubules, as
      well as membranes of specific curvature and lipid composition. Recent studies
      have shed more light on how septins interact with actin and microtubules, and
      raised the possibility that the cytoskeletal topology of septins is determined by
      their membrane specificity. Importantly, new functions have emerged for septins
      regarding the generation, maintenance and positioning of cytoskeletal networks
      with distinct organization and biochemical makeup. This Review presents new and
      past findings, and discusses septins as a unique regulatory module that instructs
      the local differentiation and positioning of distinct actin and microtubule
      networks.

PMID- 29326314
TI  - High-Density Lipoprotein Cholesterol and Mortality: Too Much of a Good Thing?
AB  - OBJECTIVE: The objective of this study was to examine the shape of the
      association between high-density lipoprotein cholesterol (HDL-C) and mortality in
      a large general population sample. APPROACH AND RESULTS: Adult participants (n=37
      059; age=57.7+/-11.9 years; 46.8% men) were recruited from general population
      household-based surveys (Health Survey for England and Scottish Health Survey).
      Individual participant data were linked with the British National Health Service
      Central Registry to record mortality. There were 2250 deaths from all causes
      during 326 016 person-years of follow-up. When compared with the reference
      category (HDL-C=1.5-1.99 mmol/L), a U-shaped association was apparent for all
      cause mortality, with elevated risk in participants with the lowest (hazard
      ratio=1.23; 95% confidence interval, 1.06, 1.44) and highest (1.25; 0.97, 1.62)
      HDL-C concentration. Associations for cardiovascular disease were linear, and
      elevated risk was observed in those with the lowest HDL-C concentration (1.49;
      1.15, 1.94). CONCLUSIONS: A U-shaped association was observed between HDL-C and
      mortality in a large general population sample.

PMID- 29326315
TI  - Plasma n-3 and n-6 Fatty Acids Are Differentially Related to Carotid Plaque and
      Its Progression: The Multi-Ethnic Study of Atherosclerosis.
AB  - OBJECTIVE: omega-3 (n-3) fatty acids (FAs) have long been considered healthful
      dietary components, yet recent clinical trials have questioned their
      cardiovascular benefits. By contrast, the omega-6 (n-6) FAs have been considered
      harmful, proatherogenic macronutrients, despite an absence of empirical evidence
      supporting this hypothesis. We aimed to determine whether plasma n-3 and n-6 FAs
      are related to risk of carotid plaque and its progression in 3327 participants of
      MESA (Multi-Ethnic Study of Atherosclerosis). APPROACH AND RESULTS: Carotid
      plaque was assessed using ultrasonography at baseline and after a median period
      of 9.5 years. Plasma phospholipid n-3 and n-6 FAs were determined using gas
      chromatography-flame ionization detection. Relative risk regression analyses
      assessed the relations of FAs with the presence or progression of carotid plaque
      adjusted for typical cardiovascular disease risk factors. At baseline, it was
      found that participants in the fourth quartile of n-3 docosahexaenoic acid showed
      a 9% lower risk of carotid plaque (P=0.05), whereas those in the second quartile
      of n-3 alpha-linolenic acid showed an 11% greater risk compared with respective
      referent quartiles (P=0.02). In prospective analyses, individuals in the top
      quartile of docosahexaenoic acid showed a 12% lower risk of carotid plaque
      progression during 9.5 years compared with those in the referent quartile
      (P=0.002). No significant relations were observed among n-6 FAs and plaque
      outcomes. No significant race/ethnicity interactions were found. CONCLUSIONS:
      These findings support docosahexaenoic acid as an atheroprotective macronutrient,
      whereas null findings for n-6 FAs challenge the view that they promote
      atherosclerosis.

PMID- 29326316
TI  - Fibronectin Containing Extra Domain A Induces Plaque Destabilization in the
      Innominate Artery of Aged Apolipoprotein E-Deficient Mice.
AB  - OBJECTIVE: Fibronectin containing extra domain A (Fn-EDA) is an endogenous ligand
      of TLR4 (toll-like receptor 4) and is abundant in the extracellular matrix of
      advanced atherosclerotic lesions in human and mice. Irrespective of sex, deletion
      of Fn-EDA reduces early atherosclerosis in apolipoprotein E-deficient (Apoe-/-)
      mice. However, the contribution of Fn-EDA in advanced atherosclerosis remains
      poorly characterized. We determined the contribution of Fn-EDA in advanced
      atherosclerotic lesions of aged (1-year-old) Apoe-/- mice. APPROACH AND RESULTS:
      Plaque composition was determined in the innominate artery, a plaque instability
      site that is known to mimic several histological features of vulnerable human
      plaques. Female Apoe-/-, Fn-EDA-/-Apoe-/-, TLR4-/-Apoe-/-, and Fn-EDA-/-TLR4-/
      Apoe-/- mice were fed a high-fat Western diet for 44 weeks. Fn-EDA-/-Apoe-/- mice
      exhibited reduced plaque size characterized by smaller necrotic cores, thick
      fibrous caps containing abundant vascular smooth muscle cells and collagen,
      reduced CD68/MMP9 (matrix metalloproteinase 9)-positive content, less
      accumulation of MMP-cleaved extracellular matrix aggrecan, and decreased vascular
      smooth muscle cell and macrophage apoptosis (P<0.05 versus Apoe-/- mice).
      Together these findings suggest that Fn-EDA induces plaque destabilization.
      Deletion of TLR4 reduced histological features of plaque instability in Apoe-/-
      mice but did not further reduce features of plaque destabilization in Fn-EDA-/
      Apoe-/- mice, suggesting that TLR4 may contribute to Fn-EDA-induced plaque
      destabilization. Fn-EDA potentiated TLR4-dependent MMP9 expression in bone marrow
      derived macrophages, suggesting that macrophage TLR4 may contribute to Fn-EDA
      mediated plaque instability. CONCLUSIONS: Fn-EDA induces histological features of
      plaque instability in established lesions of aged Apoe-/- mice. The abundance of
      Fn-EDA in advanced atherosclerotic lesions may increase the risk of plaque
      destabilization.

PMID- 29326319
TI  - Cross-infection risk in patients with bronchiectasis: a position statement from
      the European Bronchiectasis Network (EMBARC), EMBARC/ELF patient advisory group
      and European Reference Network (ERN-Lung) Bronchiectasis Network.

PMID- 29326318
TI  - Long-term benefits of airway clearance in bronchiectasis: a randomised placebo
      controlled trial.
AB  - Keeping airways clear of mucus by airway clearance techniques seems essential in
      bronchiectasis treatment, although no placebo-controlled trials or any studies
      lasting longer than 3 months have been conducted. We evaluate the efficacy of the
      ELTGOL (slow expiration with the glottis opened in the lateral posture) technique
      over a 1-year period in bronchiectasis patients with chronic expectoration in a
      randomised placebo-controlled trial.Patients were randomised to perform the
      ELTGOL technique (n=22) or placebo exercises (n=22) twice-daily
      (ClinicalTrials.gov, NCT01578681). The primary outcome was sputum volume during
      the first intervention and 24 h later. Secondary outcomes included sputum volume
      during the intervention and 24 h later at month 12, exacerbations, quality of
      life, sputum analyses, pulmonary function, exercise capacity, systemic
      inflammation, treatment adherence, and side effects.Sputum volume during
      intervention and 24 h later was higher in the ELTGOL group than in the placebo
      group both at the beginning and end of the study. Patients in the ELTGOL group
      had fewer exacerbations (p=0.042) and a clinically significant improvement in the
      St George's Respiratory Questionnaire score (p<0.001) and the Leicester Cough
      Questionnaire score compared with the placebo group (p<0.001).Twice-daily ELTGOL
      technique over 1 year in bronchiectasis patients facilitated secretion removal
      and was associated with fewer exacerbations, improved quality of life, and
      reduced cough impact.

PMID- 29326317
TI  - Comparative analysis of the safety and efficacy of intracameral cefuroxime,
      moxifloxacin and vancomycin at the end of cataract surgery: a meta-analysis.
AB  - BACKGROUND: Current practice methods are unclear as to the most safe and
      effective prophylactic pharmacotherapy and method of delivery to reduce
      postoperative endophthalmitis occurrence. METHODS: A systematic review and meta
      analysis using Meta-analysis of Observational Studies in Epidemiology guidelines
      was performed to compare the efficacy of intracameral cefuroxime, moxifloxacin
      and vancomycin in preventing postphacoemulsification cataract surgery
      endophthalmitis. A safety analysis of intracameral antibiotics was concurrently
      performed. DATA SOURCES: BIOSIS Previews, CINAHL, ClinicalTrials.gov, Cochrane
      Library, Dissertations & Theses, EMBASE, PubMed, ScienceDirect and Scopus were
      searched from inception to January 2017. Data were pooled using a random effects
      model. All articles were individually reviewed and data were extracted by two
      independent reviewers. Funnel plot, risk of bias and quality of evidence analyses
      were performed. RESULTS: Seventeen studies with over 900 000 eyes were included,
      which favoured the use of intracameral antibiotics at the end of cataract surgery
      (OR 0.20; 95% CI 0.13 to 0.32; P<0.00001). The average weighted postoperative
      endophthalmitis incidence rates with intracameral cefuroxime, moxifloxacin and
      vancomycin were 0.0332%, 0.0153% and 0.0106%, respectively. Secondary analyses
      showed no difference in efficacy between intracameral plus topical antibiotics
      versus intracameral alone (P>0.3). Most studies had low to moderate risk of bias.
      The safety analysis showed minimal toxicity for moxifloxacin. Dosing errors led
      to the majority of toxicities with cefuroxime. Although rare, vancomycin was
      associated with toxic retinal events. CONCLUSION: Intracameral cefuroxime and
      moxifloxacin reduced endophthalmitis rates compared with controls with minimal or
      no toxicity events at standard doses. Additionally, intracameral antibiotics
      alone may be as effective as intracameral plus topical antibiotics.

PMID- 29326320
TI  - Lack of penetration of amikacin into saliva of tuberculosis patients.

PMID- 29326321
TI  - Tuberculosis elimination: a dream or a reality? The case of Oman.

PMID- 29326322
TI  - ELTGOL airway clearance in bronchiectasis: laying the bricks of evidence.

PMID- 29326323
TI  - Time for a longer and better life for patients with COPD.

PMID- 29326325
TI  - Breath analysis for label-free characterisation of airways disease.

PMID- 29326324
TI  - Pulmonary rehabilitation for patients with COPD during and after an exacerbation
      related hospitalisation: back to the future?

PMID- 29326327
TI  - National roll-out of latent tuberculosis testing and treatment for new migrants
      in England: a retrospective evaluation in a high-incidence area.
AB  - Latent tuberculosis infection (LTBI) screening is an important intervention for
      tuberculosis (TB) elimination in low-incidence countries and is, therefore, a key
      component of England's TB control strategy. This study describes outcomes from a
      LTBI screening programme in a high-incidence area to inform national LTBI
      screening in England and other low-incidence countries.We conducted a
      retrospective cohort study of LTBI screening among eligible migrants (from high
      incidence countries and entered the UK within the last 5 years), who were
      identified at primary-care clinics in Newham, London between August 2014 and
      August 2015. Multivariable logistic regression was used to identify factors
      associated with LTBI testing uptake, interferon-gamma release assay (IGRA)
      positivity and treatment uptake.40% of individuals offered LTBI screening
      received an IGRA test. The majority of individuals tested were 16-35 years old,
      male and born in India, Bangladesh or Pakistan. Country of birth, smoking status
      and co-morbidities were associated with LTBI testing uptake. IGRA positivity was
      32% among those tested and was significantly associated with country of birth,
      age, sex and co-morbidities.This study identifies factors associated with
      screening uptake, IGRA positivity and treatment uptake, and improves
      understanding of groups that should be supported to increase acceptability of
      LTBI testing and treatment in the community.

PMID- 29326329
TI  - Balloon pulmonary angioplasty in sarcoid-related pulmonary hypertension.

PMID- 29326328
TI  - Pulmonary rehabilitation for patients with COPD during and after an exacerbation
      related hospitalisation: back to the future?

PMID- 29326330
TI  - Program of Integrated Care for Patients with Chronic Obstructive Pulmonary
      Disease and Multiple Comorbidities (PIC COPD+): a randomised controlled trial.
AB  - We sought to evaluate the effectiveness of a multi-component, case manager-led
      exacerbation prevention/management model for reducing emergency department
      visits. Secondary outcomes included hospitalisation, mortality, health-related
      quality of life, chronic obstructive pulmonary disease (COPD) severity, COPD self
      efficacy, anxiety and depression.Two-centre randomised controlled trial
      recruiting patients with >=2 prognostically important COPD-associated
      comorbidities. We compared our multi-component intervention including
      individualised care/action plans and telephone consults (12-weekly then 9
      monthly) with usual care (both groups). We used zero-inflated Poisson models to
      examine emergency department visits and hospitalisation; Cox proportional hazard
      model for mortality.We randomised 470 participants (236 intervention, 234
      control). There were no differences in number of emergency department visits or
      hospital admissions between groups. We detected difference in emergency
      department visit risk, for those that visited the emergency department, favouring
      the intervention (RR 0.74, 95% CI 0.63-0.86). Similarly, risk of hospital
      admission was lower in the intervention group for those requiring hospital
      admission (RR 0.69, 95% CI 0.54-0.88). Fewer intervention patients died (21
      versus 36) (HR 0.56, 95% CI 0.32-0.95). No differences were detected in other
      secondary outcomes.Our multi-component, case manager-led exacerbation
      prevention/management model resulted in no difference in emergency department
      visits, hospital admissions and other secondary outcomes. Estimated risk of death
      (intervention) was nearly half that of the control.

PMID- 29326331
TI  - Predicting response to oxygen therapy in obstructive sleep apnoea patients using
      a 10-minute daytime test.
AB  - There is no satisfactory treatment for obstructive sleep apnoea (OSA).
      Supplemental low-flow oxygen therapy (LFO2) has been shown to reduce hypoxaemia
      and is well tolerated by patients with OSA. However, oxygen therapy may be
      beneficial only to certain subsets of patients with OSA. In this study, we
      evaluated a 10-min awake ventilatory chemoreflex test in predicting individual
      OSA response to 2 months of LFO2 therapy.At baseline, patients with OSA underwent
      ventilatory chemoreflex testing in the afternoon, prior to the overnight
      polysomnography. Subjects were reassessed with polysomnography after 2 months of
      nocturnal oxygen treatment.20 patients with OSA completed the study. After 2
      months of O2 treatment, changes in the apnoea-hypopnoea index (AHI) were
      significantly correlated with baseline CO2 ventilatory response threshold (VRT)
      and chemosensitivity (p<0.05). In predicting a fall in AHI, the area under the
      receiver operating characteristic curve (AUC) was 0.79 for VRT and 0.89 for
      chemosensitivity. When these two variables were combined in a logistic regression
      model, the prediction effect became stronger with an AUC of 0.97, sensitivity of
      0.92 and specificity of 0.83.Our awake ventilatory chemoreflex test could be
      considered a simple potential clinical tool to predict individual OSA response to
      oxygen therapy. It could provide a novel personalised medicine approach to OSA
      treatment.

PMID- 29326332
TI  - The impact of digital health technologies on tuberculosis treatment: a systematic
      review.
AB  - Digital technologies are increasingly harnessed to support treatment of persons
      with tuberculosis (TB). Since in-person directly observed treatment (DOT) can be
      resource intensive and challenging to implement, these technologies may have the
      potential to improve adherence and clinical outcomes. We reviewed the effect of
      these technologies on TB treatment adherence and patient outcomes.We searched
      several bibliographical databases for studies reporting the effect of digital
      interventions, including short message service (SMS), video-observed therapy
      (VOT) and medication monitors (MMs), to support treatment for active TB. Only
      studies with a control group and which reported effect estimates were
      included.Four trials showed no statistically significant effect on treatment
      completion when SMS was added to standard care. Two observational studies of VOT
      reported comparable treatment completion rates when compared with in-person DOT.
      MMs increased the probability of cure (RR 2.3, 95% CI 1.6-3.4) in one
      observational study, and one trial reported a statistically significant reduction
      in missed treatment doses relative to standard care (adjusted means ratio 0.58,
      95% CI 0.42-0.79).Evidence of the effect of digital technologies to improve TB
      care remains limited. More studies of better quality are needed to determine how
      such technologies can enhance programme performance.

PMID- 29326333
TI  - COMET: a multicomponent home-based disease-management programme versus routine
      care in severe COPD.
AB  - The COPD Patient Management European Trial (COMET) investigated the efficacy and
      safety of a home-based COPD disease management intervention for severe COPD
      patients.The study was an international open-design clinical trial in COPD
      patients (forced expiratory volume in 1 s <50% of predicted value) randomised 1:1
      to the disease management intervention or to the usual management practices at
      the study centre. The disease management intervention included a self-management
      programme, home telemonitoring, care coordination and medical management. The
      primary end-point was the number of unplanned all-cause hospitalisation days in
      the intention-to-treat (ITT) population. Secondary end-points included acute care
      hospitalisation days, BODE (body mass index, airflow obstruction, dyspnoea and
      exercise) index and exacerbations. Safety end-points included adverse events and
      deaths.For the 157 (disease management) and 162 (usual management) patients
      eligible for ITT analyses, all-cause hospitalisation days per year (mean+/-sd)
      were 17.4+/-35.4 and 22.6+/-41.8, respectively (mean difference -5.3, 95% CI 
      13.7 to -3.1; p=0.16). The disease management group had fewer per-protocol acute
      care hospitalisation days per year (p=0.047), a lower BODE index (p=0.01) and a
      lower mortality rate (1.9% versus 14.2%; p<0.001), with no difference in
      exacerbation frequency. Patient profiles and hospitalisation practices varied
      substantially across countries.The COMET disease management intervention did not
      significantly reduce unplanned all-cause hospitalisation days, but reduced acute
      care hospitalisation days and mortality in severe COPD patients.

PMID- 29326334
TI  - Clinical and inflammatory phenotyping by breathomics in chronic airway diseases
      irrespective of the diagnostic label.
AB  - Asthma and chronic obstructive pulmonary disease (COPD) are complex and
      overlapping diseases that include inflammatory phenotypes. Novel anti
      eosinophilic/anti-neutrophilic strategies demand rapid inflammatory phenotyping,
      which might be accessible from exhaled breath.Our objective was to capture
      clinical/inflammatory phenotypes in patients with chronic airway disease using an
      electronic nose (eNose) in a training and validation set.This was a multicentre
      cross-sectional study in which exhaled breath from asthma and COPD patients
      (n=435; training n=321 and validation n=114) was analysed using eNose technology.
      Data analysis involved signal processing and statistics based on principal
      component analysis followed by unsupervised cluster analysis and supervised
      linear regression.Clustering based on eNose resulted in five significant combined
      asthma and COPD clusters that differed regarding ethnicity (p=0.01), systemic
      eosinophilia (p=0.02) and neutrophilia (p=0.03), body mass index (p=0.04),
      exhaled nitric oxide fraction (p<0.01), atopy (p<0.01) and exacerbation rate
      (p<0.01). Significant regression models were found for the prediction of
      eosinophilic (R2=0.581) and neutrophilic (R2=0.409) blood counts based on eNose.
      Similar clusters and regression results were obtained in the validation
      set.Phenotyping a combined sample of asthma and COPD patients using eNose
      provides validated clusters that are not determined by diagnosis, but rather by
      clinical/inflammatory characteristics. eNose identified systemic neutrophilia
      and/or eosinophilia in a dose-dependent manner.

PMID- 29326335
TI  - Baclofen and sleep apnoea syndrome: analysis of VigiBase, the WHO
      pharmacovigilance database.

PMID- 29326337
TI  - Acid-Suppressive Drug Use During Pregnancy and the Risk of Childhood Asthma: A
      Meta-analysis.
AB  - CONTEXT: The association between acid-suppressive drug exposure during pregnancy
      and childhood asthma has not been well established. OBJECTIVE: To conduct a
      systematic review and meta-analysis on this association to provide further
      justification for the current studies. DATA SOURCES: We searched PubMed, Medline,
      Embase, the Cochrane Database of Systematic Reviews, EBSCO Information Services,
      Web of Science, and Google Scholar from inception until June 2017. STUDY
      SELECTION: Observational studies in which researchers assessed acid-suppressive
      drug use during pregnancy and the risk of childhood asthma were included. DATA
      EXTRACTION: Of 556 screened articles, 8 population-based studies were included in
      the final analyses. RESULTS: When all the studies were pooled, acid-suppressive
      drug use in pregnancy was associated with an increased risk of asthma in
      childhood (relative risk [RR] = 1.45; 95% confidence interval [CI] 1.35-1.56; I2
      = 0%; P < .00001). The overall risk of asthma in childhood increased among proton
      pump inhibitor users (RR = 1.34; 95% CI 1.18-1.52; I2 = 46%; P < .00001) and
      histamine-2 receptor antagonist users (RR = 1.57; 95% CI 1.46-1.69; I2 = 0%; P <
      .00001). LIMITATIONS: None of the researchers in the studies in this meta
      analysis adjusted for the full panel of known confounders in these associations.
      CONCLUSIONS: The evidence suggests that prenatal, maternal, acid-suppressive drug
      use is associated with an increased risk of childhood asthma. This information
      may help clinicians and parents to use caution when deciding whether to take acid
      suppressing drugs during pregnancy because of the risk of asthma in offspring.

PMID- 29326338
TI  - Acid Suppressant Use in Pregnancy and Asthma in Offspring: Should We Be Worried?

PMID- 29326339
TI  - Ninety-year-old man with hypereosinophilia, lymphadenopathies and pruritus.
AB  - We report a case of a 90-year-old man with hypereosinophilia, lymphadenopathies
      and skin lesions, namely lichenification and pruritus. An aetiological
      investigation was performed, and a bone marrow (BM) biopsy and aspirate showed a
      hypercellular marrow with hypereosinophilia without dysmorphia or abnormal
      elements, and the BM and inguinal node's immunophenotyping denied any presence of
      abnormal lymphoid cell population. The inguinal node biopsy revealed a
      multinodular proliferation of large cells S100 and CD1a+, and a diagnosis of
      Langerhans cell histiocytosis was made. The hypereosinophilia and skin lesions
      were managed with corticotherapy with substantial improvement of cutaneous
      lesions and lymphadenopathies and normalisation of eosinophil count. Finally, to
      define if it is a single or multisystem disease, a skin biopsy will be necessary.

PMID- 29326336
TI  - ARID5B as a critical downstream target of the TAL1 complex that activates the
      oncogenic transcriptional program and promotes T-cell leukemogenesis.
AB  - The oncogenic transcription factor TAL1/SCL induces an aberrant transcriptional
      program in T-cell acute lymphoblastic leukemia (T-ALL) cells. However, the
      critical factors that are directly activated by TAL1 and contribute to T-ALL
      pathogenesis are largely unknown. Here, we identified AT-rich interactive domain
      5B (ARID5B) as a collaborating oncogenic factor involved in the transcriptional
      program in T-ALL. ARID5B expression is down-regulated at the double-negative 2-4
      stages in normal thymocytes, while it is induced by the TAL1 complex in human T
      ALL cells. The enhancer located 135 kb upstream of the ARID5B gene locus is
      activated under a superenhancer in T-ALL cells but not in normal T cells.
      Notably, ARID5B-bound regions are associated predominantly with active
      transcription. ARID5B and TAL1 frequently co-occupy target genes and coordinately
      control their expression. ARID5B positively regulates the expression of TAL1 and
      its regulatory partners. ARID5B also activates the expression of the oncogene MYC
      Importantly, ARID5B is required for the survival and growth of T-ALL cells, and
      forced expression of ARID5B in immature thymocytes results in thymus retention,
      differentiation arrest, radioresistance, and tumor formation in zebrafish. Our
      results indicate that ARID5B reinforces the oncogenic transcriptional program by
      positively regulating the TAL1-induced regulatory circuit and MYC in T-ALL,
      thereby contributing to T-cell leukemogenesis.

PMID- 29326340
TI  - Rare cause of pulmonary cavitation in a 75-year-old man.
AB  - A 75-year-old man of Asian descent presented to the acute medical unit with signs
      and symptoms suggestive of a community-acquired pneumonia. He had multiple
      comorbidities and was relatively immunocompromised as a result. Initial
      investigations supported the diagnosis of community-acquired pneumonia
      complicated by a cavitating lung lesion, and the patient was treated as per
      hospital guidelines. He continued to deteriorate despite appropriate therapy and
      developed a hydropneumothorax, requiring the insertion of a chest drain. A
      diagnosis of pulmonary mucormycosis (Rhizopus microsporus) was made based on
      microbiology results from pleural aspirate, and patient was treated with
      intravenous antifungals. The patient was referred to the thoracic team for
      consideration of surgical intervention but was not suitable due to his multiple
      comorbidities. This case highlighted the importance of early consideration of
      fungal infection in patients with multiple risk factors and the need for
      aggressive therapy to ensure the best outcome.

PMID- 29326341
TI  - Endometrial Adenocarcinoma With Pulmonary Recurrence.

PMID- 29326342
TI  - Intradiploic cephalocele: a rare entity at a rare site.

PMID- 29326343
TI  - Cervical ganglioneuroma: clinical and radiological features of a rare tumour.

PMID- 29326344
TI  - Sternocleidomastoid tumour in neonate: fibromatosis colli.

PMID- 29326345
TI  - microRNA-452 exerts growth-suppressive activity against T-cell acute
      lymphoblastic leukemia.
AB  - T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological
      cancer. Although microRNA (miR)-452 serves as a tumor suppressor in multiple
      solid tumors, its expression and function in hematological cancers including T
      ALL is largely unknown. We measured the expression of miR-452 in 38 T-ALL and 22
      normal lymph node samples by real-time PCR analysis. The methylation levels in
      the promoter of miR-452 were determined using MethyLight assay. The effects of
      miR-452 overexpression on proliferation, cell cycle distribution, and
      tumorigenesis were explored. It was found that miR-452 expression levels were
      significantly lower in T-ALL specimens than in normal lymph node biopsies
      (P=0.0079). T-ALL specimens had a significantly higher methylation level in the
      promoter of miR-452 than normal lymph node tissues (P=0.0014). Consistently, miR
      452 was downregulated in Jurkat and Molt-4 T-ALL cells, whose expression was
      restored after treatment with a demethylation agent 5-aza-2'-deoxycytidine.
      Ectopic expression of miR-452 inhibited the proliferation of Jurkat and Molt-4
      cells and induced a G0/G1 cell cycle arrest. Overexpression of miR-452 suppressed
      the protein expression of BMI1 in T-ALL cells. Rescue experiments revealed that
      overexpression of BMI1 partially reversed the growth-suppressive effect of miR
      452 on T-ALL cells. Xenograft tumor studies confirmed that overexpression of miR
      452 suppressed tumor growth in nude mice and reduced the expression of BMI1.
      Collectively, miR-452 is epigenetically silenced and targets BMI1 to exert a
      growth suppressive activity in T-ALL. Restoration of miR-452 expression may
      represent a promising therapeutic strategy for this malignancy.

PMID- 29326346
TI  - UN pledges to tackle environmental health risks.

PMID- 29326347
TI  - Limited-stage DLBCL: it's patient selection.

PMID- 29326348
TI  - Choosing ibrutinib wisely.

PMID- 29326349
TI  - NOTCHing down a win for megakaryocytes.

PMID- 29326350
TI  - Clinicogenetic risk modeling in ATL.

PMID- 29326352
TI  - Talaromyces marneffei and dysplastic neutrophils on blood smear in newly
      diagnosed HIV.

PMID- 29326351
TI  - NK cell destiny after haploSCT with PT-Cy.

PMID- 29326353
TI  - When a marginal zone-type lymphocytosis mimics large granular lymphocytes.

PMID- 29326354
TI  - Accuracy of Dose Calibrators for 68Ga PET Imaging: Unexpected Findings in a
      Multicenter Clinical Pretrial Assessment.
AB  - We report the discovery of a systematic miscalibration during the work-up process
      for site validation of a multicenter clinical PET imaging trial using 68Ga, which
      manifested as a consistent and reproducible underestimation in the quantitative
      accuracy (assessed by SUV) of a range of PET systems from different manufacturers
      at several different facilities around Australia. Methods: Sites were asked to
      follow a strict preparation protocol to create a radioactive phantom with 68Ga to
      be imaged using a standard clinical protocol before commencing imaging in the
      trial. All sites had routinely used 68Ga for clinical PET imaging for many years.
      The reconstructed image data were transferred to an imaging core laboratory for
      analysis, along with information about ancillary equipment such as the
      radionuclide dose calibrator. Fourteen PET systems were assessed from 10 nuclear
      medicine facilities in Australia, with the aim for each PET system being to
      produce images within 5% of the true SUV. Results: At initial testing, 10 of the
      14 PET systems underestimated the SUV by 15% on average (range, 13%-23%).
      Multiple PET systems at one site, from two different manufacturers, were all
      similarly affected, suggesting a common cause. We eventually identified an
      incorrect factory-shipped dose calibrator setting from a single manufacturer as
      being the cause. The calibrator setting for 68Ga was subsequently adjusted by the
      users so that the reconstructed images produced accurate values. Conclusion: PET
      imaging involves a chain of measurements and calibrations to produce accurate
      quantitative performance. Testing of the entire chain is simple, however, and
      should form part of any quality assurance program or prequalifying site
      assessment before commencing a quantitative imaging trial or clinical imaging.

PMID- 29326356
TI  - Cerebrospinal Fluid, Hyposmia, and Dementia in Alzheimer Disease: Insights from
      Dynamic PET and a Hypothesis.

PMID- 29326355
TI  - 18F-FEDAC as a Targeting Agent for Activated Macrophages in DBA/1 Mice with
      Collagen-Induced Arthritis: Comparison with 18F-FDG.
AB  - Activated macrophages have been known to play pivotal roles in the pathogenesis
      of rheumatoid arthritis (RA). 18F-FEDAC (N-benzyl-N-methyl-2-[7,8-dihydro-7-(2
      18F-fluoroethyl)-8-oxo-2-phenyl-9H-purin-9-yl]acetamide) is a radiolabeled ligand
      for the 18-kDa translocator protein (TSPO), which is abundant in activated
      macrophages. We evaluated the feasibility of using 18F-FEDAC in a murine RA
      model. Methods: RAW 264.7 mouse macrophages were activated by lipopolysaccharide.
      TSPO expression levels in activated and inactivated macrophages were measured by
      quantitative polymerase chain reaction and Western blotting. The cellular uptake
      and specific binding of 18F-FEDAC were measured using a gamma-counter. For the in
      vivo study, collagen-induced arthritis (CIA) was developed in DBA/1 mice, and the
      clinical score for arthritis was measured regularly. 18F-FEDAC and 18F-FDG PET
      images were acquired on days 23 and 37 after the first immunization. Histologic
      examinations were performed to evaluate macrophages and TSPO expression. Results:
      We found increased TSPO messenger RNA and protein expression in activated
      macrophages. Uptake of 18F-FEDAC in activated macrophages was higher than that in
      nonactivated cells and was successfully blocked by the competitor, PK11195. In
      CIA mice, joint swelling was apparent on day 26 after the first immunization, and
      the condition worsened by day 37. 18F-FEDAC uptake by arthritic joints increased
      early on (day 23), whereas 18F-FDG uptake did not. However, 18F-FDG uptake by
      arthritic joints markedly increased at later stages (day 37) to a higher level
      than 18F-FEDAC uptake. The 18F-FEDAC uptake correlated weakly with summed
      severity score (P = 0.019, r = 0.313), whereas the 18F-FDG uptake correlated
      strongly with summed severity score (P < 0.001, r = 0.897). Histologic sections
      of arthritic joints demonstrated an influx of macrophages compared with that in
      normal joints. Conclusion:18F-FEDAC enabled the visualization of active
      inflammation sites in arthritic joints in a CIA model by targeting TSPO
      expression in activated macrophages. The results suggest the potential usefulness
      of 18F-FEDAC imaging in the early phase of RA.

PMID- 29326357
TI  - Gauging Cardiac Repair and Regeneration with New Molecular Probes.

PMID- 29326358
TI  - Targeted alpha-Therapy of Metastatic Castration-Resistant Prostate Cancer with
      225Ac-PSMA-617: Swimmer-Plot Analysis Suggests Efficacy Regarding Duration of
      Tumor Control.
AB  - The aim of this evaluation was to identify the first indicators of efficacy for
      225Ac-labeled prostate-specific membrane antigen (PSMA)-617 therapy in a
      retrospectively analyzed group of patients. Methods: Forty patients with
      metastatic castration-resistant prostate cancer were selected for treatment with
      three 100 kBq/kg cycles of 225Ac-PSMA-617 at 2-mo intervals. Prostate-specific
      antigen (PSA) and blood cell count were measured every 4 wk. PSMA PET/CT or PSMA
      SPECT/CT were used for baseline staging and imaging follow-up at month 6. Follow
      up included the duration of PSA response and radiologic progression-free survival
      at month 6. Patient histories were reviewed for the duration of previous
      treatment lines, and a swimmer plot was used to intraindividually compare the
      duration of tumor control by PSMA therapy versus prior treatment modalities.
      Results: Thirty-one of 40 patients were treated per protocol. Five patients
      discontinued treatment because of nonresponse, and 4 because of xerostomia. Of
      the 38 patients surviving at least 8 wk, 24 (63%) had a PSA decline of more than
      50%, and 33 (87%) had a PSA response of any degree. The median duration of tumor
      control under 225Ac-PSMA-617 last-line therapy was 9.0 mo; 5 patients had an
      enduring response of more than 2 y. Because all patients had advanced disease,
      this result compares favorably with the tumor control rates associated with
      earlier-phase disease; the most common preceding first-, second-, third-, and
      fourth-line therapies were abiraterone (median duration 10.0 mo), docetaxel (6.5
      mo), enzalutamide (6.5 mo), and cabazitaxel (6.0 mo), respectively. Conclusion: A
      positive response for surrogate parameters demonstrates remarkable antitumor
      activity for 225Ac-PSMA-617. Swimmer-plot analysis indicates a promising duration
      of tumor control, especially considering the unfavorable prognostic profile of
      the selected advanced-stage patients. Xerostomia was the main reason patients
      discontinued therapy or refused additional administrations and was in the same
      dimension as nonresponse; this finding indicates that further modifications of
      the treatment regimen with regard to side effects might be necessary to further
      enhance the therapeutic range.

PMID- 29326359
TI  - Doxorubicin Effect on Myocardial Metabolism as a Prerequisite for Subsequent
      Development of Cardiac Toxicity: Are There Unsuspected Confounders?

PMID- 29326360
TI  - Immuno-PET in Inflammatory Bowel Disease: Imaging CD4-Positive T Cells in a
      Murine Model of Colitis.
AB  - Inflammatory bowel diseases (IBDs) in humans are characterized in part by
      aberrant CD4-positive (CD4+) T-cell responses. Currently, identification of foci
      of inflammation within the gut requires invasive procedures such as colonoscopy
      and biopsy. Molecular imaging with antibody fragment probes could be used to
      noninvasively monitor cell subsets causing intestinal inflammation. Here, GK1.5
      cys-diabody (cDb), an antimouse CD4 antibody fragment derived from the GK1.5
      hybridoma, was used as a PET probe for CD4+ T cells in the dextran sulfate sodium
      (DSS) mouse model of IBD. Methods: The DSS mouse model of IBD was validated by
      assessing changes in CD4+ T cells in the spleen and mesenteric lymph nodes (MLNs)
      using flow cytometry. Furthermore, CD4+ T cell infiltration in the colons of
      colitic mice was evaluated using immunohistochemistry. 89Zr-labeled GK1.5 cDb was
      used to image distribution of CD4+ T cells in the abdominal region and lymphoid
      organs of mice with DSS-induced colitis. Region-of-interest analysis was
      performed on specific regions of the gut to quantify probe uptake. Colons, ceca,
      and MLNs were removed and imaged ex vivo by PET. Imaging results were confirmed
      by ex vivo biodistribution analysis. Results: An increased number of CD4+ T cells
      in the colons of colitic mice was confirmed by anti-CD4 immunohistochemistry.
      Increased uptake of 89Zr-maleimide-deferoxamine (malDFO)-GK1.5 cDb in the distal
      colon of colitic mice was visible in vivo in PET scans, and region-of-interest
      analysis of the distal colon confirmed increased activity in DSS mice. MLNs from
      colitic mice were enlarged and visible in PET images. Ex vivo scans and
      biodistribution confirmed higher uptake in DSS-treated colons (DSS, 1.8 +/- 0.40;
      control, 0.45 +/- 0.12 percentage injected dose [%ID] per organ, respectively),
      ceca (DSS, 1.1 +/- 0.38; control, 0.35 +/- 0.09 %ID per organ), and MLNs (DSS,
      1.1 +/- 0.58; control, 0.37 +/- 0.25 %ID per organ). Conclusion:89Zr-malDFO-GK1.5
      cDb detected CD4+ T cells in the colons, ceca, and MLNs of colitic mice and may
      prove useful for further investigations of CD4+ T cells in preclinical models of
      IBD, with potential to guide development of antibody-based imaging in human IBD.

PMID- 29326361
TI  - Molecular Imaging of Bacteria in Patients Is an Attractive Fata Morgana, Not a
      Realistic Option.

PMID- 29326362
TI  - 18F-PBR111 PET Imaging in Healthy Controls and Schizophrenia: Test-Retest
      Reproducibility and Quantification of Neuroinflammation.
AB  - Activated microglia express the translocator protein (TSPO) on the outer
      mitochondrial membrane. 18F-PBR111 is a second-generation PET ligand that
      specifically binds the TSPO, allowing in vivo visualization and quantification of
      neuroinflammation. The aim of this study was to evaluate whether the test-retest
      variability of 18F-PBR111 in healthy controls is acceptable to detect a psychosis
      associated neuroinflammatory signal in schizophrenia. Methods: Dynamic 90-min 18F
      PBR111 scans were obtained in 17 healthy male controls (HCs) and 11 male
      schizophrenia patients (SPs) during a psychotic episode. Prior genotyping for the
      rs6917 polymorphism distinguished high-affinity binders (HABs) and mixed-affinity
      binders (MABs). Total volume of distribution (VT) was determined from 2-tissue
      compartment modeling with vascular trapping and a metabolite-corrected plasma
      input function. A subgroup of HCs (n = 12; 4 HABs and 8 MABs) was scanned twice
      to assess absolute test-retest variability and intraclass correlation
      coefficients of the regional VT values. Differences in TSPO binding between HC
      and SP were assessed using mixed model analysis adjusting for age, genotype, and
      age*cohort. The effect of using different scan durations (VT-60 min versus VT-90
      min) was determined based on Pearson r. Data were mean +/- SD. Results: Mean
      absolute variability in VT ranged from 16% +/- 14% (19% +/- 20% HAB; 15% +/- 11%
      MAB) in the cortical gray matter to 22% +/- 15% (23% +/- 15% HAB; 22% +/- 16%
      MAB) in the hippocampus. Intraclass correlation coefficients were consistently
      between 0.64 and 0.82 for all tested regions. TSPO binding in SP compared with HC
      depended on age (cohort*age: P < 0.05) and was increased by +14% +/- 4% over the
      regions. There was a significant effect of genotype on TSPO binding, and VT of
      HABs was 31% +/- 8% (HC: 17% +/- 5%, SP: 61% +/- 14%) higher than MABs. Across
      all clinical groups, VT-60 min and VT-90 min were strongly correlated (r > 0.7, P
      < 0.0001). Conclusion:18F-PBR111 can be used for monitoring of TSPO binding, as
      shown by medium test-retest variability and reliability of VT in HCs. Microglial
      activation is present in SPs depending on age and needs to be adjusted for
      genotype.

PMID- 29326363
TI  - Research, Research, Otherwise We Are lost!

PMID- 29326364
TI  - Inflammation and PD-L1 expression in pulmonary neuroendocrine tumors.
AB  - In the light of novel cancer immune therapies, the status of antitumor
      inflammatory response and its regulation has gained much attention in patients
      with lung cancer. Ample datasets exist for non-small-cell lung cancer, but those
      for pulmonary neuroendocrine tumors are scarce and controversial. Here, tumor
      associated inflammation, CD8+ cell infiltration and PD-L1 status were evaluated
      in a cohort of 57 resected carcinoids and 185 resected neuroendocrine carcinomas
      of the lung (58 large cell carcinomas and 127 small cell carcinomas). Data were
      correlated with clinicopathological factors and survival. Moderate or high tumor
      associated inflammation was detected in 4 carcinoids (7%) and in 37
      neuroendocrine carcinomas (20%). PD-L1 immunoreactivity was seen in immune cells
      of 73 (39%) neuroendocrine carcinomas, while tumor cells were labeled in 21 (11%)
      cases. Inflammatory cells and tumor cells in carcinoids lacked any PD-L1
      expression. In neuroendocrine carcinomas, PD-L1 positivity in immune cells, but
      not in tumor cells, was associated with intratumoral CD8+ cell infiltration (P <
      0.001), as well as with the severity of tumor-associated inflammation (P <
      0.001). In neuroendocrine carcinomas, tumor-associated inflammation and PD-L1
      positivity in immune cells correlated with prolonged survival and the latter
      factor was also an independent prognosticator (P < 0.01, hazard ratio 0.4 for
      overall survival, P < 0.001 hazard ratio 0.4 for disease-free survival). Taken
      together, in neuroendocrine tumors, antitumor inflammatory response and PD-L1
      expression are largely restricted to neuroendocrine carcinomas, and in this tumor
      entity, PD-L1 expression in inflammatory cells is positively correlated to
      patient survival.

PMID- 29326365
TI  - Disruption of Mitochondria-Associated Endoplasmic Reticulum Membrane (MAM)
      Integrity Contributes to Muscle Insulin Resistance in Mice and Humans.
AB  - Modifications of the interactions between endoplasmic reticulum (ER) and
      mitochondria, defined as mitochondria-associated membranes (MAMs), were recently
      shown to be involved in the control of hepatic insulin action and glucose
      homeostasis, but with conflicting results. Whereas skeletal muscle is the primary
      site of insulin-mediated glucose uptake and the main target for alterations in
      insulin-resistant states, the relevance of MAM integrity in muscle insulin
      resistance is unknown. Deciphering the importance of MAMs on muscle insulin
      signaling could help to clarify this controversy. Here, we show in skeletal
      muscle of different mice models of obesity and type 2 diabetes (T2D) a marked
      disruption of ER-mitochondria interactions as an early event preceding
      mitochondrial dysfunction and insulin resistance. Furthermore, in human myotubes,
      palmitate-induced insulin resistance is associated with a reduction of structural
      and functional ER-mitochondria interactions. Importantly, experimental increase
      of ER-mitochondria contacts in human myotubes prevents palmitate-induced
      alterations of insulin signaling and action, whereas disruption of MAM integrity
      alters the action of the hormone. Lastly, we found an association between altered
      insulin signaling and ER-mitochondria interactions in human myotubes from obese
      subjects with or without T2D compared with healthy lean subjects. Collectively,
      our data reveal a new role of MAM integrity in insulin action of skeletal muscle
      and highlight MAM disruption as an essential subcellular alteration associated
      with muscle insulin resistance in mice and humans. Therefore, reduced ER
      mitochondria coupling could be a common alteration of several insulin-sensitive
      tissues playing a key role in altered glucose homeostasis in the context of
      obesity and T2D.

PMID- 29326367
TI  - Organic Anion Transporter 2 Mediates Hepatic Uptake of Tolbutamide, a CYP2C9
      Probe Drug.
AB  - Tolbutamide is primarily metabolized by CYP2C9, and, thus, is frequently applied
      as a clinical probe substrate for CYP2C9 activity. However, there is a marked
      discrepancy in the in vitro-in vivo extrapolation of its metabolic clearance,
      implying a potential for additional clearance mechanisms. The goal of this study
      was to evaluate the role of hepatic uptake transport in the pharmacokinetics of
      tolbutamide and to identify the molecular mechanism thereof. Transport studies
      using singly transfected cells expressing six major hepatic uptake transporters
      showed that tolbutamide is a substrate to organic anion transporter 2 (OAT2)
      alone with transporter affinity [Michaelis-Menten constant (Km)] of 19.5 +/- 4.3
      uM. Additionally, OAT2-specific transport was inhibited by ketoprofen (an OAT2
      inhibitor) and 1 mM rifamycin SV (pan inhibitor), but not by cyclosporine and
      rifampicin (OAT polypeptides/Na+-taurocholate cotransporting polypeptide
      inhibitors). Uptake studies in primary human hepatocytes confirmed the
      predominant role of OAT2 in the active uptake with significant inhibition by
      rifamycin SV and ketoprofen, but not by the other inhibitors. Concentration
      dependent uptake was noted in human hepatocytes with active transport
      characterized by Km and Vmax values of 39.3 +/- 6.6 uM and 426 +/- 30 pmol/min
      per milligram protein, respectively. Bottom-up physiologically based
      pharmacokinetic modeling was employed to verify the proposed role of OAT2
      mediated hepatic uptake. In contrast to the rapid equilibrium (CYP2C9-only)
      model, the permeability-limited (OAT2-CYP2C9 interplay) model better described
      the plasma concentration-time profiles of tolbutamide. Additionally, the latter
      well described tolbutamide pharmacokinetics in carriers of CYP2C9 genetic
      variants and quantitatively rationalized its known drug-drug interactions. Our
      results provide first-line evidence for the role of OAT2-mediated hepatic uptake
      in the pharmacokinetics of tolbutamide, and imply the need for additional
      clinical studies in this direction.

PMID- 29326368
TI  - Correction: Antenatal thoracoamniotic shunting in congenitalcystic adenomatoid
      malformation.

PMID- 29326366
TI  - Highly Proliferative alpha-Cell-Related Islet Endocrine Cells in Human Pancreata.
AB  - The proliferative response of non-beta islet endocrine cells in response to type
      1 diabetes (T1D) remains undefined. We quantified islet endocrine cell
      proliferation in a large collection of nondiabetic control and T1D human
      pancreata across a wide range of ages. Surprisingly, islet endocrine cells with
      abundant proliferation were present in many adolescent and young-adult T1D
      pancreata. But the proliferative islet endocrine cells were also present in
      similar abundance within control samples. We queried the proliferating islet
      cells with antisera against various islet hormones. Although pancreatic
      polypeptide, somatostatin, and ghrelin cells did not exhibit frequent
      proliferation, glucagon-expressing alpha-cells were highly proliferative in many
      adolescent and young-adult samples. Notably, alpha-cells only comprised a
      fraction (~1/3) of the proliferative islet cells within those samples; most
      proliferative cells did not express islet hormones. The proliferative hormone
      negative cells uniformly contained immunoreactivity for ARX (indicating alpha
      cell fate) and cytoplasmic Sox9 (Sox9Cyt). These hormone-negative cells
      represented the majority of islet endocrine Ki67+ nuclei and were conserved from
      infancy through young adulthood. Our studies reveal a novel population of highly
      proliferative ARX+ Sox9Cyt hormone-negative cells and suggest the possibility of
      previously unrecognized islet development and/or lineage plasticity within
      adolescent and adult human pancreata.

PMID- 29326369
TI  - Successful treatment of postural orthostatic tachycardia and mast cell activation
      syndromes using naltrexone, immunoglobulin and antibiotic treatment.
AB  - A patient with severe postural orthostatic tachycardia syndrome (POTS) and mast
      cell activation syndrome (MCAS) received immunotherapy with low-dose naltrexone
      (LDN) and intravenous immunoglobulin (IVIg) and antibiotic therapy for small
      intestinal bacterial overgrowth (SIBO). A dramatic and sustained response was
      documented. The utility of IVIg in autoimmune neuromuscular diseases has been
      published, but clinical experience with POTS is relatively unknown and has not
      been reported in MCAS. As a short-acting mu-opioid antagonist, LDN paradoxically
      increases endorphins which then bind to regulatory T cells which regulate T
      lymphocyte and B-lymphocyte production and this reduces cytokine and antibody
      production. IVIg is emerging as a promising therapy for POTS. Diagnosis and
      treatment of SIBO in POTS is a new concept and appears to play an important role.

PMID- 29326370
TI  - A rare case of giant cell tumour (GCT) of bone with lung metastases.
AB  - A case of 16-year-old girl with giant cell tumour of right fibula is presented to
      us with bilateral lung metastases. In view of widespread bilateral lung
      metastatic lesions, the patient was given multimodality treatment. Chemotherapy
      followed by radiotherapy to the local site as well as lung bath has been given
      and has shown good response.

PMID- 29326371
TI  - Mycoplasma pneumoniae infection presenting as stroke and meningoencephalitis with
      aortic and subclavian aneurysms without pulmonary involvement.
AB  - A 39-year-old Philipino man presented with acute onset fever and headache.
      Neurological examination was normal except for neck stiffness. There was no
      history of chest pain, cough or breathlessness. Cerebrospinal fluid (CSF) showed
      a mild increase in protein with normal sugar and lymphocytic pleocytosis. CSF PCR
      for herpes simplex and varicella zoster virus was negative. He developed acute
      right haemiplegia a week after hospitalisation. MRI showed acute infarct in the
      left centrum semiovale. His angiogram showed aneurysm in the left subclavian
      artery and aortic arch. The mycoplasma antibody test came positive with very high
      titres, while rest of the workup was negative. He was treated with azithromycin
      and his symptoms improved completely.He was asymptomatic on follow-up after a
      month. His repeat immunoglobulin G mycoplasma antibody titre showed elevation.
      Mycoplasma infection is a treatable cause of meningoencephalitis and stroke
      secondary to vasculitis. Arterial aneurysms are known to occur with mycoplasma
      infection although rare.

PMID- 29326372
TI  - Caecal duplication cyst: a rare cause of neonatal intestinal obstruction.
AB  - We report a rare case of duplication cyst of the caecum responsible for an
      intestinal obstruction in a 5-day-old newborn. Preoperatively, we suspected the
      diagnosis of enteric duplication as ultrasonography demonstrated a cystic mass in
      the right iliac fossa, and laparotomy confirmed an obstructive caecal mass which
      was resected and an end-to-end anastomosis was performed. The neonate completely
      recovered with an uneventful follow-up.

PMID- 29326373
TI  - Hepatitis A infections in men who have sex with men using HIV PrEP in Paris.
AB  - The current hepatitis A outbreak in Europe is largely involving men having sex
      with multiple male partners. The objective of the present report was to warn
      teams dealing against the persistent risk of viral and bacterial sexually
      transmitted infection (STIs) in patients receiving HIV pre-exposure prophylaxis
      (PrEP). We have notified and investigated three cases of acute hepatitis A virus
      (HAV) infection in people receiving HIV PrEP in our clinic between December 2016
      and March 2017. The patients were not epidemiologically related, had no recent
      travel history to HAV endemic areas, reported multiple STIs during this period
      and had not been vaccinated against HAV. They were all identified as genotype A,
      strain VRD_521_2016 virus.Large-scale vaccination against viral hepatitis is
      recommended in men having sex with men, especially in those using PrEP, as PrEP
      is used by people who have high-risk sexual behaviour.

PMID- 29326374
TI  - Beware of air.

PMID- 29326375
TI  - Group B streptococcus septic arthritis of the hip following spontaneous abortion.
AB  - Group B streptococcus (GBS) infection of the hip in otherwise healthy adults is a
      rare entity that is previously only reported following peripartum gynaecological
      procedure and instrumentation. We report a case of infection of the hip with GBS
      following spontaneous abortion. Delay in identification of infection as the cause
      of pain ultimately leads to irreversible joint destruction. This case report will
      heighten the awareness of the first contact providers as well as orthopaedic
      surgeons to be more vigilant for possible septic complications associated with
      gynaecological procedures/complications and subsequent painful joints. To our
      knowledge, this is the only case report showing association of GBS infection in
      hip associated with spontaneous abortion.

PMID- 29326376
TI  - Arm amputation secondary to squamous cell carcinoma: exotic expeditions leading
      to a delayed diagnosis?

PMID- 29326377
TI  - Lymphatic malformation with acquired Horner syndrome in an infant.
AB  - An infant presented with right upper eyelid ptosis and was subsequently diagnosed
      with acquired Horner syndrome. Further evaluation revealed a right-sided
      cervicothoracic lymphatic malformation. At 13 weeks of age, the child underwent
      percutaneous intracystic sclerotherapy with a mixture of sodium tetradecyl
      sulphate and ethanol. Twenty-one weeks after initial treatment, ophthalmic
      examination showed complete resolution of the blepharoptosis and pupillary
      miosis. Percutaneous sclerotherapy not only effectively treated the space
      occupying lymphatic malformation but also reversed the Horner syndrome that was
      presumably induced by neural tension (more likely) or compression.

PMID- 29326378
TI  - The Casper Stent System for carotid artery stenosis.
AB  - PURPOSE: To report the results of a retrospective analysis of prospectively
      collected data evaluating the safety and efficacy of a double layer stent
      engineered for carotid artery occlusive disease. METHODS: Between January 2014
      and February 2017, 138 patients (25.4% women; median age 71 years) underwent
      Casper stent implantation for carotid artery stenosis. Eligibility criteria
      included stenosis >70% of vessel diameter (or >50% diameter with ulceration) in
      symptomatic patients or asymptomatic patients with >80% stenosis at the carotid
      bifurcation or in the proximal internal carotid artery. For all procedures, a
      distal embolic protection device was used. The primary endpoint was the rate of
      90 day major adverse neurological events, defined as minor stroke, major stroke,
      or death by independent neurological assessment. RESULTS: Stent deployment was
      completed successfully in all cases without documented technical failure. There
      were no adverse neurological events or mortalities within 90 days. One
      thromboembolic occlusion of a small distal branch of the anterior cerebral artery
      occurred during the procedure and resolved with systemic recombinant tissue
      plasminogen activator administration. New ischemic lesions, all clinically
      silent, were seen in 6.5% of patients on post-procedure cerebral MRI. CONCLUSION:
      The Casper carotid stent demonstrated safety and efficacy in the treatment of
      carotid stenosis, with no technical failures and no adverse neurological events
      seen throughout the 90 day follow-up period. Its double layer structure seems to
      combine adequate plaque scaffolding with high vessel adaptability.

PMID- 29326379
TI  - Blood pressure levels post mechanical thrombectomy and outcomes in non
      recanalized large vessel occlusion patients.
AB  - OBJECTIVE: Permissive hypertension may benefit patients with non-recanalized
      large vessel occlusion (nrLVO) post mechanical thrombectomy (MT) by maintaining
      brain perfusion. Data evaluating the impact of post-MT blood pressure (BP) levels
      on outcomes in nrLVO patients are scarce. We investigated the association of the
      post-MT BP course with safety and efficacy outcomes in nrLVO. METHODS: Hourly
      systolic BP (SBP) and diastolic BP (DBP) values were prospectively recorded for
      24 hours following MT in consecutive nrLVO patients. Maximum, minimum, and mean
      BP levels were documented. Three-month functional independence (FI) was defined
      as modified Rankin Scale (mRS) scores of 0-2. RESULTS: A total of 88 nrLVO
      patients were evaluated post MT. Patients with FI had lower maximum SBP (160+/-19
      mmHg vs 179+/-23 mmHg; P=0.001) and higher minimum SBP levels (119+/-12 mmHg vs
      108+/-25 mmHg; P=0.008). Maximum SBP (183+/-20 mmHg vs 169+/-23 mmHg; P=0.008)
      and DBP levels (105+/-20 mmHg vs 89+/-18 mmHg; P=0.001) were higher in patients
      who died at 3 months while minimum SBP values were lower (102+/-28 mmHg vs 115+/
      16 mmHg; P=0.007). On multivariable analyses, both maximum SBP (OR per 10 mmHg
      increase: 0.55, 95% CI 0.39 to 0.79; P=0.001) and minimum SBP (OR per 10 mmHg
      increase: 1.64, 95% CI 1.04 to 2.60; P=0.033) levels were independently
      associated with the odds of FI. Maximum DBP (OR per 10 mmHg increase: 1.61; 95%
      CI 1.10 to 2.36; P=0.014) and minimum SBP (OR per 10 mmHg increase: 0.65, 95% CI
      0.47 to 0.90; P=0.009) values were independent predictors of 3-month mortality.
      CONCLUSIONS: Our study demonstrates that wide BP excursions from the mean during
      the first 24 hours post MT are associated with worse outcomes in patients with
      nrLVO.

PMID- 29326380
TI  - Neuroendovascular management of emergent large vessel occlusion: update on the
      technical aspects and standards of practice by the Standards and Guidelines
      Committee of the Society of NeuroInterventional Surgery.

PMID- 29326382
TI  - 'Quality is never an accident'.

PMID- 29326381
TI  - B1a B cells require autophagy for metabolic homeostasis and self-renewal.
AB  - Specific metabolic programs are activated by immune cells to fulfill their
      functional roles, which include adaptations to their microenvironment. B1 B cells
      are tissue-resident, innate-like B cells. They have many distinct properties,
      such as the capacity to self-renew and the ability to rapidly respond to a
      limited repertoire of epitopes. The metabolic pathways that support these
      functions are unknown. We show that B1 B cells are bioenergetically more active
      than B2 B cells, with higher rates of glycolysis and oxidative phosphorylation,
      and depend on glycolysis. They acquire exogenous fatty acids and store lipids in
      droplet form. Autophagy is differentially activated in B1a B cells, and deletion
      of the autophagy gene Atg7 leads to a selective loss of B1a B cells caused by a
      failure of self-renewal. Autophagy-deficient B1a B cells down-regulate critical
      metabolic genes and accumulate dysfunctional mitochondria. B1 B cells, therefore,
      have evolved a distinct metabolism adapted to their residence and specific
      functional properties.

PMID- 29326383
TI  - Gove sets out key areas for farming reform.

PMID- 29326384
TI  - Are animal research trials fit for purpose?

PMID- 29326386
TI  - Conservation success story under poisoning threat.
AB  - One of the world's longest and most successful continuous conservation projects
      to re-introduce the red kite to England and Scotland is being hampered by
      poisoning.

PMID- 29326390
TI  - The trend of raw meat-based diets: risks to people and animals.

PMID- 29326391
TI  - Zoonotic bacteria and parasites found in raw meat-based diets for cats and dogs.
AB  - Feeding raw meat-based diets (RMBDs) to companion animals has become increasingly
      popular. Since these diets may be contaminated with bacteria and parasites, they
      may pose a risk to both animal and human health. The purpose of this study was to
      test for the presence of zoonotic bacterial and parasitic pathogens in Dutch
      commercial RMBDs. We analysed 35 commercial frozen RMBDs from eight different
      brands. Escherichia coli serotype O157:H7 was isolated from eight products (23
      per cent) and extended-spectrum beta-lactamases-producing E coli was found in 28
      products (80 per cent). Listeria monocytogenes was present in 19 products (54 per
      cent), other Listeria species in 15 products (43 per cent) and Salmonella species
      in seven products (20 per cent). Concerning parasites, four products (11 per
      cent) contained Sarcocystis cruzi and another four (11 per cent) S tenella In two
      products (6 per cent) Toxoplasma gondii was found. The results of this study
      demonstrate the presence of potential zoonotic pathogens in frozen RMBDs that may
      be a possible source of bacterial infections in pet animals and if transmitted
      pose a risk for human beings. If non-frozen meat is fed, parasitic infections are
      also possible. Pet owners should therefore be informed about the risks associated
      with feeding their animals RMBDs.

PMID- 29326393
TI  - Current status of avian influenza in Europe and the UK.

PMID- 29326394
TI  - The value of good first-opinion practice.

PMID- 29326395
TI  - Ram health and welfare.

PMID- 29326396
TI  - It's so much harder to be your own vet.
AB  - This month a vet describes dealing with the loss of their own pet and how this
      impacts on their work.

PMID- 29326397
TI  - Roger Barry Clampitt.
AB  - A clinical pathologist whose outstanding contribution to the profession was to
      invent the first reliable clinical biochemistry analyser for use in practice.

PMID- 29326400
TI  - Treatment of cutaneous angiosarcoma of the scalp and face in Chinese patients:
      local experience at a regional hospital in Hong Kong.
AB  - INTRODUCTION: Angiosarcoma is a rare aggressive sarcoma that occurs mostly in the
      skin of the head and neck in the elderly population. The optimal management is
      dubious and most studies are from Caucasian populations. We aimed to examine the
      treatment and outcome of this disease in Chinese patients. METHODS: Data of
      patients with histopathologically verified cutaneous angiosarcoma of the head and
      neck during December 1997 to September 2016 were retrieved from our hospital
      cancer registry. The demographic data, clinicopathological information, modality
      of treatment, and outcomes were reviewed. RESULTS: During the study period, 17
      Chinese patients were treated. Their median age was 81 years. The tumours were
      present in the scalp only (n=11), face only (n=4), or both scalp and face (n=2).
      Only two patients had distant metastases. The modalities of treatment were
      surgery (n=6), surgery and adjuvant radiotherapy (n=1), palliative radiotherapy
      (n=5), or palliative chemotherapy (n=3). The remaining two patients refused any
      treatment initially. Of the seven patients treated surgically, there were four
      local and two regional recurrences. The median time to relapse was 7.5 months.
      Overall, 16 patients had died; causes of death were disease-related in 12 whereas
      four other patients died of inter-current illnesses. One patient was still living
      with the disease. The median overall survival was 11.1 months and the longest
      overall survival was 42 months. CONCLUSION: The outcome of angiosarcoma in our
      series is poor. A high index of suspicion is mandatory for prompt diagnosis.
      Adjuvant radiotherapy is recommended following surgery. The benefit and role of
      systemic treatment in various combinations with surgery or radiotherapy require
      further study.

PMID- 29326401
TI  - Efficacy and tolerability of trastuzumab emtansine in advanced human epidermal
      growth factor receptor 2-positive breast cancer.
AB  - INTRODUCTION: The management of human epidermal growth factor receptor 2 (HER2)
      positive breast cancer has changed dramatically with the introduction and
      widespread use of HER2-targeted therapies. There is, however, relatively limited
      real-world information about the effectiveness and safety of trastuzumab
      emtansine (T-DM1) in Hong Kong Chinese patients. We assessed the efficacy and
      toxicity profiles among local patients with HER2-positive advanced breast cancer
      who had received T-DM1 therapy in the second-line setting and beyond. METHODS:
      This retrospective study involved five local centres that provide service for
      over 80% of the breast cancer population in Hong Kong. The study period was from
      December 2013 to December 2015. Patients were included if they had recurrent or
      metastatic histologically confirmed HER2+ breast cancer who had progressed after
      at least one line of anti-HER2 therapy including trastuzumab. Patients were
      excluded if they received T-DM1 as first-line treatment for recurrent or
      metastatic HER2+ breast cancer. Patient charts including biochemical and
      haematological profiles were reviewed for background information, T-DM1 response,
      and toxicity data. Adverse events were documented during chemotherapy and 28 days
      after the last dose of medication. RESULTS: Among 37 patients being included in
      this study, 28 (75.7%) had two or more lines of anti-HER2 agents and 26 (70.3%)
      had received two or more lines of palliative chemotherapy. Response assessment
      revealed that three (8.1%) patients had a complete response, eight (21.6%) a
      partial response, 11 (29.7%) a stable disease, and 12 (32.4%) a progressive
      disease; three patients could not be assessed. The median duration of response
      was 17.3 (95% confidence interval, 8.4-24.8) months. The clinical benefit rate
      (complete response + partial response + stable disease, >=12 weeks) was 37.8%
      (95% confidence interval, 22.2%-53.5%). The median progression-free survival was
      6.0 (95% confidence interval, 3.3- 9.8) months and the median overall survival
      had not been reached by the data cut-off date. Grade 3 or 4 toxicities included
      thrombocytopaenia (13.5%), raised alanine transaminase (8.1%), anaemia (5.4%),
      and hypokalaemia (2.7%). No patient died as a result of toxicities. CONCLUSIONS:
      In patients with HER2-positive advanced breast cancer who have been heavily
      pretreated with anti-HER2 agents and cytotoxic chemotherapy, T-DM1 is well
      tolerated and provided a meaningful progression-free survival of 6 months and an
      overall survival that has not been reached. Further studies to identify
      appropriate patient subgroups are warranted.

PMID- 29326402
TI  - Ageing in individuals with intellectual disability: issues and concerns in Hong
      Kong.
AB  - INTRODUCTION: The increasing longevity of people with intellectual disability is
      testimony to the positive developments occurring in medical intervention.
      Nonetheless, early-onset age-related issues and concerns cause deterioration of
      their overall wellbeing. This paper aimed to explore the issues and concerns
      about individuals with intellectual disability as they age. METHODS: Articles
      that discussed people older than 30 years with an intellectual disability and
      those that identified ageing health issues and concerns were included. Only
      studies reported in English from 1996 to 2016 were included. We searched PubMed,
      Google Scholar, and Science Direct using the terms 'intellectual disability',
      'ageing', 'cognitive impairment', 'health', and 'screening'. RESULTS: Apart from
      the early onset of age-related health problems, dementia is more likely to
      develop by the age of 40 years in individuals with intellectual disability.
      Geriatric services to people with intellectual disability, however, are only
      available for those aged 60 years and older. Cognitive instruments used for the
      general population are not suitable for people with intellectual disability
      because of floor effects. In Hong Kong, the Chinese version of the Dementia
      Screening Questionnaire for Individuals with Intellectual Disabilities is the
      only validated instrument for people with intellectual disability. The use of
      appropriate measurement tools to monitor the progression of age-related
      conditions in individuals with intellectual disability is of great value.
      CONCLUSIONS: Longitudinal assessment of cognition and function in people with
      intellectual disability is vital to enable early detection of significant
      deterioration. This allows for therapeutic intervention before substantial damage
      to the brain occurs such as dementia that hastens cognitive and functional
      decline.

PMID- 29326404
TI  - [Effects of Breastfeeding Interventions on Breastfeeding Rates at 1, 3 and 6
      Months Postpartum: A Systematic Review and Meta-Analysis].
AB  - PURPOSE: This study was a systematic review and meta-analysis designed to
      evaluate the effects of breastfeeding intervention on breastfeeding rates.
      METHODS: Based on the guidelines of the Preferred Reporting Items for Systematic
      Reviews and Meta-analyses (PRISMA), a systematic search was conducted using eight
      core electronic databases and other sources including gray literature from
      January 9 to 19, 2017. Two reviewers independently select the studies and
      assessed methodological risk of bias of studies using the Cochrane criteria. The
      topics of breastfeeding interventions were analyzed using descriptive analysis
      and the effects of intervention were meta-analyzed using the Review Manager 5.2
      software. RESULTS: A total of 16 studies were included in the review and 15 were
      included for meta-analysis. The most frequently used intervention topics were the
      importance of good latch-on and frequency of feeding and determining adequate
      intake followed. The pooled total effect of breastfeeding intervention was 1.08
      (95% CI 1.03~1.13). In the subgroup analysis, neither pre-nor post-childbirth
      intervention was effective on the breastfeeding rates at 1, 3, and 6 months, and
      neither group nor individual interventions had an effect. Only the 1 month
      breastfeeding rate was found to be affected by the individual intervention with
      the persistent strategies 1.21 (95% CI 1.04~1.40). CONCLUSION: Effective
      breastfeeding interventions are needed to help the mother to start breastfeeding
      after childbirth and continue for at least six months. It should be programmed
      such that individuals can acquire information and specific breastfeeding skills.
      After returning home, there should be continuous support strategies for
      breastfeeding as well as managing various difficulties related to childcare.

PMID- 29326403
TI  - Resveratrol, an Nrf2 activator, ameliorates aging-related progressive renal
      injury.
AB  - BACKGROUND: Two important issues in the aging kidney are mitochondrial
      dysfunction and oxidative stress. An Nrf2 activator, resveratrol, is known to
      have various effects. Resveratrol may prevent inflammation and oxidative stress
      by activating Nrf2 and SIRT1 signaling. We examined whether resveratrol could
      potentially ameliorate the cellular condition, such as renal injury due to
      cellular oxidative stress and mitochondrial dysfunction caused by aging. METHODS:
      Male 18-month-old C57BL/6 mice were used. Resveratrol (40 mg/kg) was administered
      to aged mice for 6 months. We compared histological changes, oxidative stress,
      and aging-related protein expression in the kidney between the resveratrol
      treated group (RSV) and the control group (cont). We performed experiments using
      small-interfering RNAs (siRNAs) for Nrf2 and SIRT1 in cultured HK2 cells.
      RESULTS: Resveratrol improved renal function, proteinuria, histological changes
      and inflammation in aging mice. Also, expression of Nrf2-HO-1-NOQ-1 signaling and
      SIRT1-AMPK-PGC-1alpha signaling was increased in the RSV group. Transfection with
      Nrf2 and SIRT1 siRNA prevented resveratrol-induced anti-oxidative effect in HK2
      cells in media treated with H2O2. CONCLUSIONS: Activation of the Nrf2 and SIRT1
      signaling pathways ameliorated oxidative stress and mitochondrial dysfunction.
      Pharmacological targeting of Nrf2 signaling molecules may reduce the pathologic
      changes of aging in the kidney.

PMID- 29326405
TI  - [The Relationships among Chemotherapy-Induced Nausea and Vomiting (CINV), Non
      Pharmacological Coping Methods, and Nutritional Status in Patients with
      Gynecologic Cancer].
AB  - PURPOSE: Chemotherapy-induced nausea and vomiting (CINV) can cause severe
      malnutrition. However, relationships between CINV levels, non-pharmacological
      coping methods, and nutritional status of female cancer patients have rarely been
      investigated. Therefore, this study aimed to analyze their relationships in
      gynecologic cancer patients. METHODS: Participants receiving a highly and
      moderately emetogenic chemotherapy were recruited. The level of CINV was assessed
      using a numeric rating scale. Coping methods were determined using multiple
      choice self-report questionnaires and categorized into seven types for
      statistical analysis. Nutritional status was evaluated using biochemical and
      anthropometric parameters. RESULTS: Among all the 485 patients, 200 eligible
      inpatients were included. Despite the administration of prophylactic antiemetics,
      157 patients (78.5%) still experienced CINV, and several used nonmedically
      recommended coping methods, such as just enduring the symptom or rejecting food
      intake. A total of 181 patients (90.5%) had nutritional disorders. Although the
      level of CINV was indirectly related to the occurrence of nutritional disorders,
      patients who rejected food (beta=1.57, p=.023) and did not use physical measures
      (beta= -1.23, p=.041) as coping methods were under the high risk of nutritional
      disorders. CONCLUSION: Korean gynecologic cancer patients had high levels of CINV
      and were at high risk of nutritional disorders, which may be related to the use
      of nonscientific coping methods, possibly due to cultural backgrounds and lack of
      proper nutritional program. Therefore, developing a culturally appropriate
      educational program for the cancer patients with CINV is urgently needed.

PMID- 29326406
TI  - [Effect of Visiting and a Smartphone Application Based Infection Prevention
      Education Program for Child Care Teachers: A Non-Randomized Controlled Trial].
AB  - PURPOSE: This study was performed to develop an infection prevention education
      program for child care teachers and to verify its effects. METHODS: The study was
      conducted using a nonequivalent control group with a pretest-posttest design.
      Four private daycare centers (2 centers per city) that were alike in terms of the
      number of children by age, number of child care teachers, and child care
      environment were chosen. Participants were assigned to the experimental group
      (n=20) or control group (n=20). As a part of the program, visiting education (90
      min) was provided in the 1st week, and smartphone application education (10 min)
      was provided thrice a week, in the 2nd and 3rd weeks. RESULTS: Child care
      teachers' self-efficacy for infection prevention revealed a significant
      interaction effect between the group and time of measurement (F=21.62, p<.001).
      In terms of infection prevention behavior, a significant difference was observed
      between the experimental and control groups (z=-5.36, p<.001). CONCLUSION: The
      program implemented in this study was effective in improving the infection
      prevention self-efficacy and infection prevention behavior of child care
      teachers. Thus, this program may be effective in enhancing their infection
      control.

PMID- 29326407
TI  - [The Effects of Smart Program for Patients Who Underwent Percutaneous Coronary
      Intervention (SP-PCI) on Disease-Related Knowledge, Health Behavior, and Quality
      of Life: A Non-Randomized Controlled Trial].
AB  - PURPOSE: To identify the effects of a smart program for the patients who
      underwent percutaneous coronary intervention (SP-PCI) on coronary disease-related
      knowledge, health behaviors, and quality of life. METHODS: A nonequivalent
      control group with a non-synchronized design was utilized and 48 participants
      (experimental=22, control=26) were recruited from a university hospital in
      Gyeongsang area from May to December, 2016. The 12-week SP-PCI consisted of self
      study of health information using smart phone applications (1/week), walking
      exercise (>5/week) using smart band, feedback using Kakao talk (2/week), and
      telephone counseling (1/week). Patients in the control group received usual care
      from their primary health care providers and a brief health education with basic
      self-management brochure after the PCI. Data were analyzed using the SPSS 21.0
      program through descriptive statistics, chi2 test, and t-test. RESULTS: After the
      12-week SP-PCI, the experimental group showed higher levels of coronary disease
      related knowledge (t=2.43, p=.019), heart-related health behaviors (t=5.96,
      p<.001), regular exercise (Z=-4.47, p<.001), and quality of life-MCS (t=3.04,
      p=.004) and showed lower levels of stress (Z=-3.53, p<.001) and sodium intake (t=
      4.43, p<.001) than those in the control group. There were no significant group
      differences in medication adherence and food intake in total energy, lipids, and
      cholesterol. CONCLUSION: The suggested SP-PCI provided easy access and cost
      effective intervention for patients after PCI and improved their knowledge of the
      disease, performance of health behaviors, and quality of life. Further study with
      a wider population is needed to evaluate the effects of SP-PCI on disease
      recurrence and quality of life for patients after PCI.

PMID- 29326408
TI  - [Association between Emotional Labor, Emotional Dissonance, Burnout and Turnover
      Intention in Clinical Nurses: A Multiple-Group Path Analysis across Job
      Satisfaction].
AB  - PURPOSE: This study was conducted to investigate the influence of emotional
      labor, emotional dissonance, and burnout on nurse's turnover intention and
      examine the effect of job satisfaction on the relationships among emotional
      labor, emotional dissonance, burnout, and turnover intention. METHODS: The sample
      consisted of 350 nurses recruited from 6 general hospitals in 2 cities in Korea.
      A multiple-group analysis was utilized. Data were analyzed using SPSS statistics
      23 and AMOS 20. RESULTS: In the path analysis, turnover intention was directly
      related to burnout in clinical nurses who had a high job satisfaction (beta=.24,
      p=.003), while it was indirectly related to emotional dissonance (beta=.13,
      p=.002). In the multiple-group path analysis, turnover intention was directly
      related to emotional dissonance (beta=.18, p=.033) and burnout (beta=.26, p=.002)
      for nurses with low job satisfaction. CONCLUSION: These results indicate that
      manuals and guidelines to alleviate the negative effects of emotional labor,
      emotional dissonance, and burnout, and to increase job satisfaction are strongly
      required to reduce turnover intention in nurses at the organizational level as
      well as at the individual level.

PMID- 29326409
TI  - [Life Experiences of Uninfected Women Living with HIV-Infected Husbands: A
      Phenomenological Study].
AB  - PURPOSE: This study aimed to understand the meaning and essence of the life
      experiences of uninfected women living with HIV-infected husbands. METHODS: This
      qualitative study adopted van Manen's hermeneutic phenomenological method. Study
      participants were 8 females whose husband had been diagnosed with HIV for longer
      than 6 months, who had known about their husband's infection for more than 6
      months, who were in a legal or common-law marriage and were living with their
      husbands at the time of interview for this study, and whose HIV antibody test
      results were negative. Data were collected from in-depth individual interviews
      with the participants from May to August 2016, and from related idiomatic
      expressions, literature, artwork, and phenomenological references. RESULTS: The
      following essential themes were identified regarding the life experiences of
      uninfected women living with HIV-infected husbands: 'experiencing an abrupt
      change that came out of the blue and caused confusion', 'accepting one's fate and
      making desperate efforts to maintain one's family', 'dealing with a heavy burden
      alone', 'experiencing the harsh reality and fearful future', and 'finding
      consolation in the ordeal'. CONCLUSION: This study provided a holistic and in
      depth understanding of the meaning and essence of the life experiences of
      uninfected women living with HIV-infected husbands. Thus, this study recognizes
      these unnoticed women as new nursing subjects. Further, the present findings can
      be used as important basic data for the development of nursing interventions and
      national policy guidelines for uninfected women living with HIV-infected
      husbands.

PMID- 29326410
TI  - [Factors Predicting the Interface Pressure Related to Pressure Injury in
      Intensive Care Unit Patients].
AB  - PURPOSE: Interface pressure is a factor that contributes to the occurrence of
      pressure injuries. This study aimed to investigate interface pressure at common
      sites of pressure injury (occipital, gluteal and peritrochanteric areas), to
      explore the relationships among risk factors, skin condition and interface
      pressure, and to identify risk factors influencing interface pressure. METHODS: A
      total of 100 patients admitted to the intensive care unit were enrolled at a
      tertiary teaching hospital in Korea. Interface pressure was recorded by a
      scanning aid device (PalmQ). Patient data regarding age, pulmonary disease,
      Braden Scale score, body mass index, serum albumin, hemoglobin, mean blood
      pressure, body temperature, and oxygen saturation were included as risk factors.
      Data collected from July to September 2016 were analyzed using binary logistic
      regression. RESULTS: The mean interface pressure of the occipital, gluteal, and
      right and left peritrochanteric areas were 37.96 (+/-14.90), 41.15 (+/-16.04),
      53.44 (+/-24.67), and 54.33 (+/-22.80) mmHg, respectively. Predictive factors for
      pressure injuries in the occipital area were age >=70 years (OR 3.45, 95%
      confidence interval [CI]: 1.19~9.98), serum albumin deficit (OR 2.88, 95% CI:
      1.00~8.26) and body temperature >=36.5C (OR 3.12, 95% CI: 1.17~8.17); age >=70
      years (OR 2.81, 95% CI: 1.10~7.15) in the right peritrochanteric area; and body
      temperature >=36.5C (OR 2.86, 95% CI: 1.17~6.98) in the left peritrochanteric
      area. CONCLUSION: Our findings suggest that old age, hypoalbuminemia, and high
      body temperature may be contributory factors to increasing interface pressure;
      therefore, careful assessment and nursing care of these patients are needed to
      prevent pressure injury. Further studies are needed to establish cutoff values of
      interface pressure for patients with pressure ulcers.

PMID- 29326411
TI  - [Semantic Network Analysis of Online News and Social Media Text Related to
      Comprehensive Nursing Care Service].
AB  - PURPOSE: As comprehensive nursing care service has gradually expanded, it has
      become necessary to explore the various opinions about it. The purpose of this
      study is to explore the large amount of text data regarding comprehensive nursing
      care service extracted from online news and social media by applying a semantic
      network analysis. METHODS: The web pages of the Korean Nurses Association (KNA)
      News, major daily newspapers, and Twitter were crawled by searching the keyword
      'comprehensive nursing care service' using Python. A morphological analysis was
      performed using KoNLPy. Nodes on a 'comprehensive nursing care service' cluster
      were selected, and frequency, edge weight, and degree centrality were calculated
      and visualized with Gephi for the semantic network. RESULTS: A total of 536 news
      pages and 464 tweets were analyzed. In the KNA News and major daily newspapers,
      'nursing workforce' and 'nursing service' were highly rated in frequency, edge
      weight, and degree centrality. On Twitter, the most frequent nodes were 'National
      Health Insurance Service' and 'comprehensive nursing care service hospital.' The
      nodes with the highest edge weight were 'national health insurance,' 'wards
      without caregiver presence,' and 'caregiving costs.' 'National Health Insurance
      Service' was highest in degree centrality. CONCLUSION: This study provides an
      example of how to use atypical big data for a nursing issue through semantic
      network analysis to explore diverse perspectives surrounding the nursing
      community through various media sources. Applying semantic network analysis to
      online big data to gather information regarding various nursing issues would help
      to explore opinions for formulating and implementing nursing policies.

PMID- 29326412
TI  - [Identifying Latent Classes of Risk Factors for Coronary Artery Disease].
AB  - PURPOSE: This study aimed to identify latent classes based on major modifiable
      risk factors for coronary artery disease. METHODS: This was a secondary analysis
      using data from the electronic medical records of 2,022 patients, who were newly
      diagnosed with coronary artery disease at a university medical center, from
      January 2010 to December 2015. Data were analyzed using SPSS version 20.0 for
      descriptive analysis and Mplus version 7.4 for latent class analysis. RESULTS:
      Four latent classes of risk factors for coronary artery disease were identified
      in the final model: 'smoking-drinking', 'high-risk for dyslipidemia', 'high-risk
      for metabolic syndrome', and 'high-risk for diabetes and malnutrition'. The
      likelihood of these latent classes varied significantly based on socio
      demographic characteristics, including age, gender, educational level, and
      occupation. CONCLUSION: The results showed significant heterogeneity in the
      pattern of risk factors for coronary artery disease. These findings provide
      helpful data to develop intervention strategies for the effective prevention of
      coronary artery disease. Specific characteristics depending on the subpopulation
      should be considered during the development of interventions.

PMID- 29326413
TI  - [Impact of Increased Supply of Newly Licensed Nurses on Hospital Nurse Staffing
      and Policy Implications].
AB  - PURPOSE: This study aimed to analyze the impact of increasing the supply of newly
      licensed nurses on improving the hospital nurse staffing grades for the period of
      2009~2014. METHODS: Using public administrative data, we analyzed the effect of
      newly licensed nurses on staffing in 1,594 hospitals using Generalized Estimating
      Equation (GEE) ordered logistic regression, and of supply variation on improving
      staffing grades in 1,042 hospitals using GEE logistic regression. RESULTS: An
      increase of one newly licensed nurse per 100 beds in general units had
      significantly lower odds of improving staffing grades (grades 6~0 vs. 7) (odds
      ratio=0.95, p=.005). The supply of newly licensed nurses increased by 32% from
      2009 to 2014, and proportion of hospitals whose staffing grade had improved, not
      changed, and worsened was 19.1%, 70.1%, and 10.8% respectively. Compared to 2009,
      the supply variation of newly licensed nurses in 2014 was not significantly
      related to the increased odds of improving staffing grades in the region
      (OR=1.02, p=.870). CONCLUSION: To achieve a balance in the regional supply and
      demand for hospital nurses, compliance with nurse staffing legislation and
      revisions in the nursing fee differentiation policy are needed. Rather than
      relying on increasing nurse supply, retention policies for new graduate nurses
      are required to build and sustain competent nurse workforce in the future.

PMID- 29326414
TI  - [Effect of Debriefing Based on the Clinical Judgment Model on Simulation Based
      Learning Outcomes of End-of-Life Care for Nursing Students: A Non-Randomized
      Controlled Trial].
AB  - PURPOSE: This study was conducted to identify effects of debriefing based on the
      clinical judgment model for nursing students on their knowledge, skill
      performance, clinical judgment, self-confidence and learner satisfaction during
      simulation based end-of-life care (ELC) education. METHODS: Simulation based ELC
      education was developed in six steps as follows: selection of learning subjects
      and objects, development of learning tools, a trial run of simulation-based
      education, students' skill training, and evaluators' training. Forty-eight senior
      nursing students (25 in the experimental group and 23 in the control group)
      participated in the simulation-based ELC education using a high-fidelity
      simulator. Debriefing based on the clinical judgment was compared with the usual
      debriefing. RESULTS: ANCOVA showed that there were differences in knowledge
      (F=4.81, p=.034), skill performance (F=68.33, p<.001), clinical judgment
      (F=18.33, p<.001) and self-confidence (F=4.85, p=.033), but no difference in
      satisfaction (t=-0.38, p=.704) between the experimental and control groups.
      CONCLUSION: This study found that debriefing based on the clinical judgement
      model is effective for supporting nursing students for reflecting on clinical
      judgment and improving their diverse competencies in complex clinical settings
      such as ELC.

PMID- 29326415
TI  - Factors Affecting Early School-Age Children's Subjective Happiness: Using the
      Actor-Partner Interdependence Model of Parental Variables.
AB  - PURPOSE: The present study is a descriptive cross-sectional study of cause-and
      effect relationship, which used the 7(th) year data of the Panel Study on Korean
      Children, to investigate the effects of parenting stress, depression, and family
      interactions of the parents of early school-age children on children's subjective
      happiness. METHODS: The present study included data of 1419 pairs of parents who
      participated in the mother and father survey of the Panel Study on Korean
      Children. The effects of parenting stress, depression, and parental family
      interactions on children's subjective happiness were analyzed as actor and
      partner effects using path analysis. RESULTS: Parenting stress had an actor
      effect on depression; maternal parenting stress (beta=-.21, p<.001) and
      depression (beta=-.30, p<.001) had an actor effect on maternal family
      interaction; and paternal parenting stress (beta=-.18, p<.001) and depression
      (beta=-.17, p<.001) had a partner effect on maternal family interaction. Paternal
      parenting stress was found to have an actor effect on paternal family interaction
      (beta=-.30, p<.001), and parental depression was found to have actor effect
      (beta=-.23, p<.001) and maternal depression had a partner effect on paternal
      family interactions (beta=-.22, p<.001). Children's subjective happiness was
      found to have a statistically significant relationship with maternal family
      interaction (beta=.40, p<.001). CONCLUSION: The significance of the study is in
      its provision of basic data for adjusting parents' family interactions that are
      closely related to the growth and development of children by confirming the
      effect of parents' parenting stress, depression, and family interaction on
      children's subjective happiness.

PMID- 29326417
TI  - Factors Causing Disagreement between Measured and Calculated Low Density
      Lipoprotein-Cholesterol (LDL-C) in Clinical Laboratory Services.
AB  - BACKGROUND Since measured low density lipoprotein-cholesterol (LDL-C) has been
      available in clinical laboratories, there have been concern about the
      disagreement between measured and calculated LDL-C and the factors causing their
      disagreement. MATERIAL AND METHODS Serum lipid concentrations were collected from
      1,339 medical records of patients admitted to hospital between 2013 and 2015.
      They were grouped by their total cholesterol (TC), triglycerides (TG), and high
      density lipoprotein-cholesterol (HDL-C) concentrations and the agreement between
      measured and calculated LDL-C was statistically analyzed. RESULTS A strong
      relationship was found between measured and calculated LDL-C. Significantly
      disagreements between measured and calculated LDL-C were found in all groups in
      2013 and 2014 when lipids were analyzed by Cobas C501. Disagreements found in
      groups of low TG and low HDL-C concentrations in 2015 were when lipids were
      analyzed by Abbott Architect ci8200. In groups of calculated LDL-C <1.81 mmol/L,
      around 80% had the measured LDL-C >1.81 mmol/L. Among various atherogenic
      indices, non-HDL-C showed the strongest relationship with LDL-C, while TC to HDL
      C ratio showed the strongest agreement with the LDL-C. CONCLUSIONS The
      disagreement between measured and calculated LDL-C in a clinical laboratory
      seemed to depend on the analytical system used, and was probably associated with
      individual laboratory variations.

PMID- 29326416
TI  - Strategies to Restore Adenosine Triphosphate (ATP) Level After More than 20 Hours
      of Cold Ischemia Time in Human Marginal Kidney Grafts.
AB  - BACKGROUND The persisting organ shortage in the field of transplantation
      recommends the use of marginal kidneys which poorly tolerate ischemic damage.
      Adenosine triphosphate (ATP) depletion during cold ischemia time (CIT) is
      considered crucial for graft function. We tested different strategies of kidney
      perfusion before transplantation in the attempt to improve the technique.
      MATERIAL AND METHODS Twenty human discarded kidneys from donors after brain death
      and with at least 20 hours of CIT were randomized to the following experimental
      groups (treatment time three-hours at 4 degrees C): a) static cold storage (CS);
      b) static cold hyperbaric oxygenation (Hyp); c) hypothermic perfusion (PE); d)
      hypothermic perfusion in hyperbaric oxygenation (PE-Hyp); and e) hypothermic
      oxygenated perfusion (PE-O2). RESULTS Histological results showed that perfusion
      with or without oxygen did not produce any endothelial damage. A depletion of ATP
      content following the preservation procedure was observed in CS, PE, and Hyp,
      while PE-Hyp and PE-O2 were associated with a net increase of ATP content with
      respect to baseline level. In addition, PE-Hyp was associated with a significant
      downregulation of endothelial isoform of nitric oxide synthase (eNOS) gene
      expression and of hypoxia inducible factor-1alpha (HIF-1alpha). CONCLUSIONS
      Hyperbaric or normobaric oxygenation with perfusion improves organ metabolic
      preservation compared to other methods. This approach may prevent the onset of
      delayed graft function, but clinical trials are needed to confirm this.

PMID- 29326418
TI  - A Case of Right-Sided Direct Carotid Cavernous Fistula: A Diagnostic Challenge.
AB  - BACKGROUND Carotid cavernous fistulas (CCFs) are rare potentially sight
      threatening abnormal connections between carotid artery and cavernous sinus. CASE
      REPORT We report a case of CCF in an 83-year-old female, who presented with
      swollen and painful right eye. The patient was initially treated with empiric
      antibiotics for suspected peri-orbital cellulitis, as noted clinically and in
      computed tomography (CT) orbits. However, lack of clinical improvement, physical
      finding of orbital bruit/thrill, and enlarged superior ophthalmic vein in
      magnetic resonance (MR) orbits suggest alternate diagnoses. Eventually, CT
      angiogram (CTA) and carotid-arteriography confirmed the diagnosis of right-sided
      direct CCF, which was subsequently treated with endovascular embolization. Not
      only does this case highlight the importance of CCF, which could be a
      differential diagnosis of swollen red eye, it also addresses the vital importance
      of physical examination in modern medicine despite the seemingly promising
      technologies. CONCLUSIONS Internists should have a low threshold of clinical
      suspicion for CCF in a patient with swollen red eyes in order to provide timely
      and proper management.

PMID- 29326420
TI  - Fasting and glucose induced thermogenesis in response to three ambient
      temperatures: a randomized crossover trial in the metabolic syndrome.
AB  - BACKGROUND/OBJECTIVES: Cold exposure increases thermogenesis and could improve
      insulin sensitivity. We hypothesized a blunted response in the metabolic syndrome
      (MetS). SUBJECTS/METHODS: Twenty older adults 59 +/- 10.4 years (with MetS,
      MetS+, n = 9; without MetS, MetS-, n = 11) completed a randomized crossover
      design of 3.5 h exposures to 20, 25 and 27  degrees C on three visits. After an
      hour's rest at the desired temperature, resting metabolic rate (RMR), respiratory
      quotient (RQ), forearm to fingertip gradients (FFG), and in the ear temperature
      (IET) were measured over 30 min. An oral glucose tolerance test followed, and
      serial measurements were continued for 2 h. Venous blood was sampled for clinical
      chemistry, irisin, and fibroblast growth factor 21(FGF21). A mixed model ANCOVA
      adjusted data for age, gender, fat mass, fat-free mass and seasonality. RESULTS:
      There was a significant MetS*temperature interaction where adjusted RMR was
      significantly higher in MetS+ compared to MetS- by 12% at 20  degrees C and by 6%
      at 25  degrees C, but similar at 27  degrees C. FFG increased and IET decreased
      with decreasing temperature to the same extent in both groups. Fasting irisin and
      FGF21 did not vary with temperature but the former was significantly higher in
      MetS-. Adjusted postprandial RQ and insulin to glucose ratios were significantly
      higher at 20  degrees C relative to 25  degrees C. Partial correlation analysis
      of differences between 27 and 20  degrees C indicated significant positive
      relationships between fasting as well as postprandial RQ and the respective
      changes in irisin and FGF21. CONCLUSIONS: There could be an upward shift of the
      TNZ in MetS+, but this needs reevaluation.

PMID- 29326419
TI  - Evaluation of Multislice Spiral Computed Tomography Perfusion Imaging for the
      Efficacy of Preoperative Concurrent Chemoradiotherapy in Middle-aged and Elderly
      Patients with Locally Advanced Gastric Cancer.
AB  - BACKGROUND This study aimed to investigate the predictive value of multislice
      spiral computed tomography (MSCT) perfusion imaging for the efficacy of
      preoperative concurrent chemoradiotherapy (CCRT) in middle-aged and elderly
      patients with locally advanced gastric cancer (LAGC). MATERIAL AND METHODS One
      hundred twenty-six middle-aged and elderly patients with LAGC were selected. MSCT
      was performed before and after CCRT to obtain perfusion parameters: blood flow
      volume (BF), blood volume (BV), mean transit time (MTT), and permeability surface
      (PS). After CCRT, according to Response Evaluation Criteria in Solid Tumors
      (RECIST), patients were categorized into the effective group and the ineffective
      group. Overall survival rate was measured by Kaplan-Meier analysis. ROC curve was
      applied to evaluate the predictive value of perfusion parameters. Multiple
      logistic regression analysis was applied to analyze the association of perfusion
      parameters with the efficacy of preoperative treatment. RESULTS Tumor volume
      reduction rates of the effective and ineffective groups were 59.23+/-8.53% and
      10.41+/-3.36%. BF, BV, and PS values in the effective group were significantly
      decreased after CCRT. ROC curves indicated high sensitivities and specificities
      of BF value (79.00%, 73.44%), BV value (71.00%, 75.00%), and PS value (82.30%,
      90.63%). The incidence rate of weakness and anorexia in the effective group was
      much higher than that in the ineffective group. Patients with low BF, BV, and PS
      values (less their optimal cutoff values) had longer survival times than these
      with high BF, BV, and PS values. CONCLUSIONS MSCT might have predictive values
      for the efficacy of preoperative CCRT in the treatment of LAGC.

PMID- 29326421
TI  - Vitamin D3-fortified milk did not affect glycemic control, lipid profile, and
      anthropometric measures in patients with type 2 diabetes, a triple-blind
      randomized clinical trial.
AB  - BACKGROUND/OBJECTIVES: The effect of vitamin D on glycemic status of diabetes
      patients is controversial. The objective was to assess the effect of vitamin D3
      fortified milk on cardiometabolic markers of patients with type 2 diabetes.
      SUBJECTS/METHODS: In this randomized triple-blind, placebo-controlled trial, 102
      patients (34 males and 68 females) aged 31-74 years with type 2 diabetes were
      randomized to receive either 250 ml unfortified or 250 ml 1000 IU vitamin D3
      fortified milk daily for 9 weeks. Anthropometric characteristics, blood pressure,
      and serum levels of glucose, insulin, and lipids were determined at baseline and
      after 9 weeks. RESULTS: Serum 25-hydroxy vitamin D concentrations improved in the
      fortified milk group compared to the control group (+14 +/- 20 vs. +4 +/- 17
      ng/ml; P = 0.001). Both groups showed significant increases in serum calcium (P <
      0.01) and decreases in total cholesterol, waist and hip circumference, and
      systolic and diastolic blood pressure (P < 0.001). Also, there was a significant
      reduction in body mass index of fortified milk group (P < 0.001). None of these
      changes were statistically significant between the two groups. Glycosylated
      hemoglobin (HbA1c) significantly decreased in both groups with a more remarkable
      reduction in the plain milk consumers, making a significant between-group
      difference (7.5% compared to 3.1%; P = 0.01). CONCLUSIONS: Overall, daily
      consumption of one cup of milk containing 1000 IU vitamin D3 for 9 weeks
      substantially improved vitamin D deficiency in patients with type 2 diabetes but
      it did not affect cardiometabolic parameters over that of plain milk.

PMID- 29326422
TI  - WFPHA: World Federation of Public Health Associations.

PMID- 29326423
TI  - Peripheral neuropathies: Subcutaneous immunoglobulin - the future of CIDP
      treatment?

PMID- 29326425
TI  - Unified understanding of MS course is required for drug development.

PMID- 29326424
TI  - Assessing treatment outcomes in multiple sclerosis trials and in the clinical
      setting.
AB  - Increasing numbers of drugs are being developed for the treatment of multiple
      sclerosis (MS). Measurement of relevant outcomes is key for assessing the
      efficacy of new drugs in clinical trials and for monitoring responses to disease
      modifying drugs in individual patients. Most outcomes used in trial and clinical
      settings reflect either clinical or neuroimaging aspects of MS (such as relapse
      and accrual of disability or the presence of visible inflammation and brain
      tissue loss, respectively). However, most measures employed in clinical trials to
      assess treatment effects are not used in routine practice. In clinical trials,
      the appropriate choice of outcome measures is crucial because the results
      determine whether a drug is considered effective and therefore worthy of further
      development; in the clinic, outcome measures can guide treatment decisions, such
      as choosing a first-line disease-modifying drug or escalating to second-line
      treatment. This Review discusses clinical, neuroimaging and composite outcome
      measures for MS, including patient-reported outcome measures, used in both trials
      and the clinical setting. Its aim is to help clinicians and researchers navigate
      through the multiple options encountered when choosing an outcome measure.
      Barriers and limitations that need to be overcome to translate trial outcome
      measures into the clinical setting are also discussed.

PMID- 29326427
TI  - Severe steatosis induces portal hypertension by systemic arterial hyporeactivity
      and hepatic vasoconstrictor hyperreactivity in rats.
AB  - Non-alcoholic fatty liver disease (NAFLD) has become the most prevalent chronic
      liver disease. The presence of portal hypertension has been demonstrated in NAFLD
      prior to development of inflammation or fibrosis, and is a result of extrahepatic
      and intrahepatic factors, principally driven by vascular dysfunction. An
      increased intrahepatic vascular resistance potentially contributes to progression
      of NAFLD via intralobular hypoxia. However, the exact mechanisms underlying
      vascular dysfunction in NAFLD remain unknown. This study investigates systemic
      hemodynamics and both aortic and intrahepatic vascular reactivity in a rat model
      of severe steatosis. Wistar rats were fed a methionine-choline-deficient diet,
      inducing steatosis, or control diet for 4 weeks. In vivo hemodynamic
      measurements, aortic contractility studies, and in situ liver perfusion
      experiments were performed. The mean arterial blood pressure was lower and portal
      blood pressure was higher in steatosis compared to controls. The maximal
      contraction force in aortic rings from steatotic rats was markedly reduced
      compared to controls. While blockade of nitric oxide (NO) production did not
      reveal any differences, cyclooxygenase (COX) blockade reduced aortic reactivity
      in both controls and steatosis, whereas effects were more pronounced in controls.
      Effects could be attributed to COX-2 iso-enzyme activity. In in situ liver
      perfusion experiments, exogenous NO donation or endogenous NO stimulation reduced
      the transhepatic pressure gradient (THPG), whereas NO synthase blockade increased
      the THPG only in steatosis, but not in controls. Alpha-1-adrenergic stimulation
      and endothelin-1 induced a significantly more pronounced increase in THPG in
      steatosis compared to controls. Our results demonstrate that severe steatosis,
      without inflammation or fibrosis, induces portal hypertension and signs of a
      hyperdynamic circulation, accompanied by extrahepatic arterial hyporeactivity and
      intrahepatic vascular hyperreactivity. The arterial hyporeactivity seems to be NO
      independent, but appears to be mediated by specific COX-2-related mechanisms.
      Besides, the increased intrahepatic vascular resistance in steatosis appears not
      to be NO-related but rather to vasoconstrictor hyperreactivity.

PMID- 29326428
TI  - Human germline gene editing: Recommendations of ESHG and ESHRE.
AB  - Technological developments in gene editing raise high expectations for clinical
      applications, first of all for somatic gene editing but in theory also for
      germline gene editing (GLGE). GLGE is currently not allowed in many countries.
      This makes clinical applications in these countries impossible now, even if GLGE
      would become safe and effective. What were the arguments behind this legislation,
      and are they still convincing? If a technique can help to avoid serious genetic
      disorders, in a safe and effective way, would this be a reason to reconsider
      earlier standpoints? The European Society of Human Reproduction and Embryology
      (ESHRE) and the European Society of Human Genetics (ESHG) together developed a
      Background document and Recommendations to inform and stimulate ongoing societal
      debates. After consulting its membership and experts, this final version of the
      Recommendations was endorsed by the Executive Committee and the Board of the
      respective Societies in May 2017. Taking account of ethical arguments, we argue
      that both basic and pre-clinical research regarding GLGE can be justified, with
      conditions. Furthermore, while clinical GLGE would be totally premature, it might
      become a responsible intervention in the future, but only after adequate pre
      clinical research. Safety of the child and future generations is a major concern.
      Future discussions must also address priorities among reproductive and potential
      non-reproductive alternatives, such as PGD and somatic editing, if that would be
      safe and successful. The prohibition of human germline modification, however,
      needs renewed discussion among relevant stakeholders, including the general
      public and legislators.

PMID- 29326426
TI  - mRNA vaccines - a new era in vaccinology.
AB  - mRNA vaccines represent a promising alternative to conventional vaccine
      approaches because of their high potency, capacity for rapid development and
      potential for low-cost manufacture and safe administration. However, their
      application has until recently been restricted by the instability and inefficient
      in vivo delivery of mRNA. Recent technological advances have now largely overcome
      these issues, and multiple mRNA vaccine platforms against infectious diseases and
      several types of cancer have demonstrated encouraging results in both animal
      models and humans. This Review provides a detailed overview of mRNA vaccines and
      considers future directions and challenges in advancing this promising vaccine
      platform to widespread therapeutic use.

PMID- 29326430
TI  - EMT in cancer.
AB  - Similar to embryonic development, changes in cell phenotypes defined as an
      epithelial to mesenchymal transition (EMT) have been shown to play a role in the
      tumorigenic process. Although the first description of EMT in cancer was in cell
      cultures, evidence for its role in vivo is now widely reported but also actively
      debated. Moreover, current research has exemplified just how complex this
      phenomenon is in cancer, leaving many exciting, open questions for researchers to
      answer in the future. With these points in mind, we asked four scientists for
      their opinions on the role of EMT in cancer and the challenges faced by
      scientists working in this fast-moving field.

PMID- 29326429
TI  - Responsible innovation in human germline gene editing: Background document to the
      recommendations of ESHG and ESHRE.
AB  - Technological developments in gene editing raise high expectations for clinical
      applications, including editing of the germline. The European Society of Human
      Reproduction and Embryology (ESHRE) and the European Society of Human Genetics
      (ESHG) together developed a Background document and Recommendations to inform and
      stimulate ongoing societal debates. This document provides the background to the
      Recommendations. Germline gene editing is currently not allowed in many
      countries. This makes clinical applications in these countries impossible now,
      even if germline gene editing would become safe and effective. What were the
      arguments behind this legislation, and are they still convincing? If a technique
      could help to avoid serious genetic disorders, in a safe and effective way, would
      this be a reason to reconsider earlier standpoints? This Background document
      summarizes the scientific developments and expectations regarding germline gene
      editing, legal regulations at the European level, and ethics for three different
      settings (basic research, preclinical research and clinical applications). In
      ethical terms, we argue that the deontological objections (e.g., gene editing
      goes against nature) do not seem convincing while consequentialist objections
      (e.g., safety for the children thus conceived and following generations) require
      research, not all of which is allowed in the current legal situation in European
      countries. Development of this Background document and Recommendations reflects
      the responsibility to help society understand and debate the full range of
      possible implications of the new technologies, and to contribute to regulations
      that are adapted to the dynamics of the field while taking account of ethical
      considerations and societal concerns.

PMID- 29326431
TI  - Impact of oncogenic pathways on evasion of antitumour immune responses.
AB  - Immunotherapeutic interventions are showing effectiveness across a wide range of
      cancer types, but only a subset of patients shows clinical response to therapy.
      Responsiveness to checkpoint blockade immunotherapy is favoured by the presence
      of a local, CD8+ T cell-based immune response within the tumour microenvironment.
      As molecular analyses of tumours containing or lacking a productive CD8+ T cell
      infiltrate are being pursued, increasing evidence is indicating that activation
      of oncogenic pathways in tumour cells can impair induction or execution of a
      local antitumour immune response. This Review summarizes our current knowledge of
      the influence of oncogenic effects on evasion of antitumour immunity.

PMID- 29326432
TI  - Yue Chen.

PMID- 29326433
TI  - Reduced Density of DISC1 Expressing Astrocytes in the Dentate Gyrus but not in
      the Subventricular Zone in Schizophrenia.

PMID- 29326434
TI  - Memory Retention Involves the Ventrolateral Orbitofrontal Cortex: Comparison with
      the Basolateral Amygdala.
AB  - This corrects the article DOI: 10.1038/npp.2017.139.

PMID- 29326435
TI  - A combined analysis of genetically correlated traits identifies 187 loci and a
      role for neurogenesis and myelination in intelligence.
AB  - Intelligence, or general cognitive function, is phenotypically and genetically
      correlated with many traits, including a wide range of physical, and mental
      health variables. Education is strongly genetically correlated with intelligence
      (rg = 0.70). We used these findings as foundations for our use of a novel
      approach-multi-trait analysis of genome-wide association studies (MTAG; Turley et
      al. 2017)-to combine two large genome-wide association studies (GWASs) of
      education and intelligence, increasing statistical power and resulting in the
      largest GWAS of intelligence yet reported. Our study had four goals: first, to
      facilitate the discovery of new genetic loci associated with intelligence;
      second, to add to our understanding of the biology of intelligence differences;
      third, to examine whether combining genetically correlated traits in this way
      produces results consistent with the primary phenotype of intelligence; and,
      finally, to test how well this new meta-analytic data sample on intelligence
      predicts phenotypic intelligence in an independent sample. By combining datasets
      using MTAG, our functional sample size increased from 199,242 participants to
      248,482. We found 187 independent loci associated with intelligence, implicating
      538 genes, using both SNP-based and gene-based GWAS. We found evidence that
      neurogenesis and myelination-as well as genes expressed in the synapse, and those
      involved in the regulation of the nervous system-may explain some of the
      biological differences in intelligence. The results of our combined analysis
      demonstrated the same pattern of genetic correlations as those from previous
      GWASs of intelligence, providing support for the meta-analysis of these
      genetically-related phenotypes.

PMID- 29326436
TI  - p66Shc deficiency enhances CXCR4 and CCR7 recycling in CLL B cells by
      facilitating their dephosphorylation-dependent release from beta-arrestin at
      early endosomes.
AB  - Neoplastic cell traffic abnormalities are central to the pathogenesis of chronic
      lymphocytic leukemia (CLL). Enhanced CXC chemokine receptor-4 (CXCR4) and
      chemokine receptor-7 (CCR7) recycling contributes to the elevated surface levels
      of these receptors on CLL cells. Here we have addressed the role of p66Shc, a
      member of the Shc family of protein adaptors the expression of which is defective
      in CLL cells, in CXCR4/CCR7 recycling. p66Shc reconstitution in CLL cells reduced
      CXCR4/CCR7 recycling, lowering their surface levels and attenuating B-cell
      chemotaxis, due to their accumulation in Rab5+ endosomes as serine
      phosphoproteins bound to beta-arrestin. This results from the ability of p66Shc
      to inhibit Ca2+ and PP2B-dependent CXCR4/CCR7 dephosphorylation and beta-arrestin
      release. We also show that ibrutinib, a Btk inhibitor that promotes leukemic cell
      mobilization from lymphoid organs, reverses the CXCR4/CCR7 recycling
      abnormalities in CLL cells by increasing p66Shc expression. These results,
      identifying p66Shc as a regulator of CXCR4/CCR7 recycling in B cells, underscore
      the relevance of its deficiency to CLL pathogenesis and provide new clues to the
      mechanisms underlying the therapeutic effects of ibrutinib.

PMID- 29326437
TI  - Insertional mutagenesis in a HER2-positive breast cancer model reveals ERAS as a
      driver of cancer and therapy resistance.
AB  - Personalized medicine for cancer patients requires a deep understanding of the
      underlying genetics that drive cancer and the subsequent identification of
      predictive biomarkers. To discover new genes and pathways contributing to
      oncogenesis and therapy resistance in HER2+ breast cancer, we performed Mouse
      Mammary Tumor Virus (MMTV)-induced insertional mutagenesis screens in ErbB2/cNeu
      transgenic mouse models. The screens revealed 34 common integration sites (CIS)
      in mammary tumors of MMTV-infected mice, highlighting loci with multiple
      independent MMTV integrations in which potential oncogenes are activated, most of
      which had never been reported as MMTV CIS. The CIS most strongly associated with
      the ErbB2-transgenic genotype was the locus containing Eras (ES cell-expressed
      Ras), a constitutively active RAS-family GTPase. We show that upon expression,
      Eras acts as a potent oncogenic driver through hyperactivation of the PI3K/AKT
      pathway, in contrast to other RAS proteins that signal primarily via the MAPK/ERK
      pathway and require upstream activation or activating mutations to induce
      signaling. We additionally show that ERAS synergistically enhances HER2-induced
      tumorigenesis and, in this role, can functionally replace ERBB3/HER3 by acting as
      a more powerful activator of PI3K/AKT signaling. Although previously reported as
      pseudogene in humans, we observed ERAS RNA and protein expression in a
      substantial subset of human primary breast carcinomas. Importantly, we show that
      ERAS induces primary resistance to the widely used HER2-targeting drugs
      Trastuzumab (Herceptin) and Lapatinib (Tykerb/Tyverb) in vivo, and is involved in
      acquired resistance via selective upregulation during treatment in vitro,
      indicating that ERAS may serve as a novel clinical biomarker for PI3K/AKT pathway
      hyperactivation and HER2-targeted therapy resistance.

PMID- 29326438
TI  - Conditional knockout of N-Myc and STAT interactor disrupts normal mammary
      development and enhances metastatic ability of mammary tumors.
AB  - The process of organ development requires a delicate balance between cellular
      plasticity and differentiation. This balance is disrupted in cancer initiation
      and progression. N-Myc and STAT interactor (NMI: human or Nmi: murine) has
      emerged as a relevant player in the etiology of breast cancer. However, a
      fundamental understanding of its relevance to normal mammary biology is lacking.
      To gain insight into its normal function in mammary gland, we generated a mammary
      specific Nmi knockout mouse model. We observed that Nmi protein expression is
      induced in mammary epithelium at the onset of pregnancy, in luminal cells and
      persists throughout lactation. Nmi knockout results in a precocious alveolar
      phenotype. These alveoli exhibit an extensive presence of nuclear beta-catenin
      and enhanced Wnt/beta-catenin signaling. The Nmi knockout pubertal ductal tree
      shows enhanced invasion of the mammary fatpad and increased terminal end bud
      numbers. Tumors from Nmi null mammary epithelium show a significant enrichment of
      poorly differentiated cells with elevated stem/progenitor markers, active
      Wnt/beta-catenin signaling, highly invasive morphology as well as, increased
      number of distant metastases. Our study demonstrates that Nmi has a distinct role
      in the differentiation process of mammary luminal epithelial cell compartment and
      developmental aberrations resulting from Nmi absence contribute to metastasis and
      demonstrates that aberration in normal developmental program can lead to
      metastatic disease, highlighting the contribution and importance of luminal
      progenitor cells in driving metastatic disease.

PMID- 29326439
TI  - Lung fibroblasts promote metastatic colonization through upregulation of stearoyl
      CoA desaturase 1 in tumor cells.
AB  - As a rate-limiting step in metastasis, metastatic colonization requires survival
      signals from supportive stroma. However, the mechanisms driving this process are
      incompletely understood. Here, we showed that the proliferation of B16F10 cells
      was promoted when cocultured with lung fibroblasts. Meanwhile, co-injection of
      B16F10 tumor cells with mouse lung fibroblasts significantly increased lung
      metastasis. Based on GEO database, we identified stearoyl-CoA desaturase 1 (SCD1)
      as a novel factor promoting metastatic colonization. Importantly, we found that
      fibroblast-secreted cathepsin B (CTSB) induced the upregulation of SCD1 in B16F10
      through Annexin A2 (ANXA2) and PI3K/Akt/mTOR pathway. The elevated SCD1 induced a
      higher ratio of monounsaturated fatty acids to saturated fatty acids in B16F10
      cells. The changes in fatty acid composition contributed to tumor cell
      proliferation and metastatic colonization. Furthermore, targeting SCD1
      effectively inhibited lung metastasis and prolonged the overall survival of mice.
      Meanwhile, the expression of SCD1 was negatively correlated with disease-free
      survival in five types of cancer patients. Collectively, our study identifies
      SCD1 as a critical modulator of tumor cell proliferation that is activated by
      cathepsin B, secreted by lung fibroblasts at the metastatic niche. Our novel
      findings provide potential therapeutic targets to prevent tumor metastasis.

PMID- 29326441
TI  - Dental caries: Caries risk assessment tools.

PMID- 29326443
TI  - Aesthetic possibilities in removable prosthodontics. Part 1: the aesthetic
      spectrum from perfect to personal.
AB  - Patients requiring dentures are getting older and as a result can be difficult to
      treat owing to various co-morbidities. This series of papers presents an overview
      of the processes involved in making removable dentures which the patient
      considers to be functionally and aesthetically successful. We hope not only to
      provide technical suggestions but also to address the issue of the clinician's,
      technician's and dental nurse's relationships with the dentally depleted patient.
      It is increasingly clear from defence organisation reports that this has a
      decisive effect on the success of this fundamentally difficult enterprise ('The
      only branch of dentistry in which you are trying to attach something to nothing'
      [Hubert Aiche]). It seems best to conduct the planning and the treatment itself
      as a co-production - the patient assuming responsibility for choosing between the
      treatment options offered and playing the leading role in making aesthetic
      decisions. Distinctions are drawn between the idealised whiter-than-white,
      'nobody-in-particular', attention-seeking denture at one extreme, and the highly
      personalised, discreet and naturalistic denture at the other. Reproducing nature
      in this way is time consuming and therefore expensive, but many 'denture
      sufferers' see it as good value. Methods for creating the latter, which through
      its very normality switches off the social observer's attention, are explained in
      detail in papers two and three of this series. These papers are designed to help
      clinicians and technicians involved in providing removable prosthodontics improve
      the appearance of their dentures and increase their patients' aesthetic
      satisfaction. They are not scientific articles in the Popperian sense of
      advancing theories which are capable of being falsified. Instead, they are an
      amalgamation of 72 years of combined experience in providing removable dental
      prostheses. We have found this branch of dentistry immensely interesting and have
      on many occasions had the satisfaction of seeing our patients' lives changed for
      the better.

PMID- 29326440
TI  - BRAF inhibition upregulates a variety of receptor tyrosine kinases and their
      downstream effector Gab2 in colorectal cancer cell lines.
AB  - BRAF mutations occur in ~10% of colorectal cancer (CRC) and are associated with
      poor prognosis. Inhibitors selective for the BRAFV600E oncoprotein, the most
      common BRAF mutant, elicit only poor response rates in BRAF-mutant CRC as single
      agents. This unresponsiveness was mechanistically attributed to the loss of
      negative feedbacks on the epidermal growth factor receptor (EGFR) and initiated
      clinical trials that combine BRAF (and MEK) inhibitors, either singly or in
      combination, with the anti-EGFR antibodies cetuximab or panitumumab. First
      results of these combinatorial studies demonstrated improved efficacy, however,
      the response rates still were heterogeneous. Here, we show that BRAF inhibition
      leads to the upregulation of a variety of receptor tyrosine kinases (RTKs) in CRC
      cell lines, including not only the EGFR, but also human epidermal growth factor
      receptor (HER) 2 and HER3. Importantly, combination of the BRAF inhibitors
      (BRAFi) vemurafenib (PLX4032), dabrafenib, or encorafenib with inhibitors dually
      targeting the EGFR and HER2 (such as lapatinib, canertinib, and afatinib)
      significantly reduced the metabolic activity and proliferative potential of CRC
      cells. This re-sensitization was also observed after genetic depletion of HER2 or
      HER3. Interestingly, BRAF inhibitors did not only upregulate RTKs, but also
      increased the abundance of the GRB2-associated binders (Gab) 1 and Gab2, two
      important amplifiers of RTK signaling. An allele-specific shRNA-mediated
      knockdown of BRAFV600E revealed that Gab2 upregulation was directly dependent on
      the loss of the oncoprotein and was not caused by an "off-target" effect of these
      kinase inhibitors. Furthermore, Gab2 and Gab2-mediated Shp2 signaling were shown
      to be functionally important in BRAFi resistance. These findings highlight
      potential new escape mechanisms to these targeted therapies and indicate that a
      broad suppression of RTK signaling might be beneficial and should be taken into
      account in future research addressing targeted therapy in BRAF-mutant CRC.

PMID- 29326446
TI  - Special feature: What role do alternative realities play in educating dentists?

PMID- 29326447
TI  - Conference report: Dentinal Tubules Inaugural Congress 2017.

PMID- 29326449
TI  - The future of failure to warn in dentistry after Montgomery: reflections from
      Australia.
AB  - The switch from the standard of the reasonable professional, to that of the
      reasonable patient in cases where it is alleged that a health professional has
      not imparted sufficient information to allow the gaining of valid consent, has
      created anxiety and confusion within the dental profession. The ruling in
      Montgomery v Lanarkshire Health Board is relatively young; there have been
      insufficient subsequent cases to truly allow a deep exploration of the real
      changes that the case will bring to the way dentistry and other health activities
      are provided. One way that light may be shone onto the significance of Montgomery
      is to examine the development of the law in this area from Australia. Australia
      and the UK share a common history and while each legal system is independent from
      the other, they hold significant influence upon each other's destiny. This
      article seeks to shed light on the true relevance of Montgomery to dentistry in
      the UK through examination of the Australian position towards the gaining of
      valid consent which has enjoyed somewhat of a head-start in this area of the law.

PMID- 29326450
TI  - Cariogenicity of e-cigarettes.

PMID- 29326453
TI  - The use of Hall technique preformed metal crowns by specialist paediatric
      dentists in the UK.
AB  - Background Hall technique preformed metal crowns (HTPMCs) have been increasing in
      use recently, but little is currently known about their use by specialists.Aim To
      investigate the views and usage of HTPMCs by UK specialist paediatric
      dentists.Design This was a prospective questionnaire-based study, distributed
      online to all specialists on the British Society of Paediatric Dentistry email
      list between July and September 2014.Results Ninety-four questionnaires were
      completed. The majority of respondents, 65% (61) worked in teaching hospitals,
      followed by community dental services, 37% (35). Ninety-six percent (89) reported
      that they used HTPMCs in their practice. Fifty-eight percent (54) used HTPMCs as
      a treatment option for restoring symptomless carious primary molars, and 15% (14)
      only when unable to provide conventional restoration. Twenty-three percent (21)
      used HTPMCs as the treatment of choice. Only 4% (4) of respondents never used
      them. Sixty percent (53) had been using HTPMCs for over five years. Seventy-six
      percent (68) would consider placing HTPMCs under inhalation sedation, and 26%
      (23) under general anaesthesia. Over 90% (85) believed that HTPMCs are suitable
      for undergraduate teaching, general practice, postgraduate training and
      specialist practice.Conclusion HTPMCs are widely used among specialist paediatric
      dentists in the UK.

PMID- 29326455
TI  - You're a BDJ reader, so join our team!

PMID- 29326454
TI  - Primary dental care: Rubber dam, feather fingers and reflection.

PMID- 29326456
TI  - Case report: coronectomy of an impacted and submerged second deciduous molar.
AB  - Coronectomy is a widely-accepted technique available for the treatment of
      impacted wisdom teeth. The fundamental principle is to prevent trauma to the
      inferior dental nerve (IDN). Many publications have demonstrated its positive
      outcomes but there is no literature available regarding coronectomy of deciduous
      teeth. This case report highlights the complex approach to managing a severely
      infraoccluded 85 in the mixed dentition of a 10-year-old female. The report
      demonstrates and discusses the combined orthodontic and oral surgical approach to
      prevent damage to the IDN and to allow space for orthodontic movement. This case
      demonstrates how nerve sparing techniques in the mixed dentition are
      achievable.Clinical relevance statement When managing severely infraoccluded and
      impacted deciduous second molars, clinicians must be aware that the option of a
      coronectomy should be considered and may be the difference between sparing the
      nerve or causing permanent injury.Objective The reader should understand that
      coronectomy is a suitable treatment option in managing impacted deciduous teeth.

PMID- 29326457
TI  - Oral health: The Sakata model.

PMID- 29326460
TI  - Aesthetic dentistry: Advancing the maxilla.

PMID- 29326462
TI  - Dentistry Jim: But not as we know it!

PMID- 29326463
TI  - A pilot study on the feasibility of training nurses to formulate multicomponent
      oral health interventions in a residential aged care facility.
AB  - '...... private practice becomes a barrier to delivering dental care in
      residential settings'.

PMID- 29326464
TI  - Notice of deaths.

PMID- 29326465
TI  - A teaching tool for establishing risk of oral health deterioration in elderly
      patients; development, implementation and evaluation at a US dental school.
AB  - Seeking to understand the complexities of the information required to assess oral
      disease risk in older patients.

PMID- 29326466
TI  - A study of oral health prevention behaviours for patients with early stage
      dementia.
AB  - Background Thorough dental prevention provided at the diagnosis of early stage
      dementia may be able to reduce the risk of dental disease before the associated
      cognitive decline takes hold.Method A questionnaire was used to see how many
      patients with a recent diagnosis of dementia were registered with a dentist and
      if they were accessing preventative dental care. The questionnaire was
      administered to patients attending Memory Assessment Services (MAS),
      approximately ten weeks after initial diagnosis. A similar questionnaire was
      conducted among MAS staff providing insight into their own personal dental care
      knowledge and behaviours.Results The total number of participants in the study
      was 51. Eighty percent were currently registered or seen regularly by a dentist.
      About half of all patients attended for regular hygienist sessions. Most patients
      did not receive dietary advice or oral hygiene instruction, nor were offered
      additional fluoride supplementation.Conclusion There was clearly scope for
      improving oral health education and prevention for dementia patients. MAS nurses
      were aware of the need for good oral health for themselves and for their
      patients, however, weren't aware of the current best evidence for prevention as
      prescribed by the Delivering Better Oral Health toolkit.

PMID- 29326468
TI  - Smoking: Developing the evidence base.

PMID- 29326471
TI  - UK professional bodies sign and publish evidence declaration.

PMID- 29326470
TI  - Dentists on film: Finding Nemo.

PMID- 29326474
TI  - Gerodontology: Denture loss in hospitals.

PMID- 29326475
TI  - Alternative sugars: Sucralose.

PMID- 29326476
TI  - Dental radiography: Root dwarfism.

PMID- 29326477
TI  - The oral health status of older patients in acute care on admission and day 7 in
      two Australian hospitals.
AB  - Good oral hygiene needed to prevent hospital acquired aspiration pneumonia in
      older patients.

PMID- 29326478
TI  - Publisher Correction: Transcriptome dynamics revealed by a gene expression atlas
      of the early Arabidopsis embryo.
AB  - In the version of this Resource originally published, the author information was
      incorrect. Jos R. Wendrich should have had a present address: Department of Plant
      Biotechnology and Bioinformatics and VIB Center for Plant Systems Biology, Ghent
      University, Technologiepark 927, 9052 Ghent, Belgium. Mark Boekschoten and Guido
      J. Hooiveld should have been affiliated to the Nutrition, Metabolism and Genomics
      Group, Division of Human Nutrition, Wageningen University, 6708 WE Wageningen,
      The Netherlands. In addition, the version of Supplementary Table 5 originally
      published with this Resource was not the intended final version and included
      inaccurate citations to the display items of the Resource, and the file format
      and extension did not match. These errors have now been corrected in all versions
      of the Resource.

PMID- 29326480
TI  - Weather-Related Hazards and Population Change: A Study of Hurricanes and Tropical
      Storms in the United States, 1980-2012.
AB  - Environmental determinists predict that people move away from places experiencing
      frequent weather hazards, yet some of these areas have rapidly growing
      populations. This analysis examines the relationship between weather events and
      population change in all U.S. counties that experienced hurricanes and tropical
      storms between 1980 and 2012. Our database allows for more generalizable
      conclusions by accounting for heterogeneity in current and past hurricane events
      and losses and past population trends. We find that hurricanes and tropical
      storms affect future population growth only in counties with growing, high
      density populations, which are only 2 percent of all counties. In those counties,
      current year hurricane events and related losses suppress future population
      growth, although cumulative hurricane-related losses actually elevate population
      growth. Low-density counties and counties with stable or declining populations
      experience no effect of these weather events. Our analysis provides a
      methodologically informed explanation for contradictory findings in prior
      studies.

PMID- 29326479
TI  - Artificial barriers prevent genetic recovery of small isolated populations of a
      low-mobility freshwater fish.
AB  - Habitat loss and fragmentation often result in small, isolated populations
      vulnerable to environmental disturbance and loss of genetic diversity. Low
      genetic diversity can increase extinction risk of small populations by elevating
      inbreeding and inbreeding depression, and reducing adaptive potential. Due to
      their linear nature and extensive use by humans, freshwater ecosystems are
      especially vulnerable to habitat loss and fragmentation. Although the effects of
      fragmentation on genetic structure have been extensively studied in migratory
      fishes, they are less understood in low-mobility species. We estimated impacts of
      instream barriers on genetic structure and diversity of the low-mobility river
      blackfish (Gadopsis marmoratus) within five streams separated by weirs or dams
      constructed 45-120 years ago. We found evidence of small-scale (<13 km) genetic
      structure within reaches unimpeded by barriers, as expected for a fish with low
      mobility. Genetic diversity was lower above barriers in small streams only,
      regardless of barrier age. In particular, one isolated population showed evidence
      of a recent bottleneck and inbreeding. Differentiation above and below the
      barrier (FST = 0.13) was greatest in this stream, but in other streams did not
      differ from background levels. Spatially explicit simulations suggest that short
      term barrier effects would not be detected with our data set unless effective
      population sizes were very small (<100). Our study highlights that, in structured
      populations, the ability to detect short-term genetic effects from barriers is
      reduced and requires more genetic markers compared to panmictic populations. We
      also demonstrate the importance of accounting for natural population genetic
      structure in fragmentation studies.

PMID- 29326481
TI  - Poverty, Homelessness, and Family Break-Up.
AB  - This study examines the extent and correlates of family separations in families
      experiencing homelessness. Of 2,307 parents recruited in family shelters across
      12 sites, a tenth were separated from partners and a quarter from one or more
      children. Additional separations before and after shelter entry and reasons, from
      parents' perspectives, were documented in qualitative interviews with a subsample
      of 80 parents. Separations were associated with economic hardship, shelter
      conditions, and family characteristics.

PMID- 29326482
TI  - Compounded Apixaban Suspensions for Enteral Feeding Tubes.
AB  - Objective: There is limited information on compounded apixaban formulations for
      administration via enteral feeding tubes. This study was designed to identify a
      suitable apixaban suspension formulation that is easy to prepare in a pharmacy
      setting, is compatible with commonly used feeding tubes, and has a beyond-use
      date of 7 days. Methods: Apixaban suspensions were prepared from commercially
      available 5-mg Eliquis tablets. Several vehicles and compounding methods were
      screened for ease of preparation, dosage accuracy, and tube compatibility. Two
      tubing types, polyurethane and polyvinyl chloride, with varying lengths and
      diameters, were included in the study. They were mounted on a peg board during
      evaluation to mimic the patient body position. A 7-day stability study of the
      selected formulation was also conducted. Results: Vehicles containing 40% to 60%
      Ora-Plus in water all exhibited satisfactory flowability through the tubes. The
      mortar/pestle compounding method was found to produce more accurate and
      consistent apixaban suspensions than the pill crusher or crushing syringe method.
      The selected formulation, 0.25 mg/mL apixaban in 50:50 Ora-Plus:water, was
      compatible with both tubing types, retaining >98% drug in posttube samples. The
      stability study also confirmed that this formulation was stable physically and
      chemically over 7 days of storage at room temperature. Conclusions: A suitable
      apixaban suspension formulation was identified for administration via enteral
      feeding tubes. The formulation consisted of 0.25 mg/mL apixaban in 50:50 Ora
      Plus:water. The stability study results supported a beyond-use date of 7 days at
      room temperature.

PMID- 29326483
TI  - Ricean over Gaussian modelling in magnitude fMRI Analysis-Added Complexity with
      Negligible Practical Benefits.
AB  - It is well-known that Gaussian modeling of functional Magnetic Resonance Imaging
      (fMRI) magnitude time-course data, which are truly Rice-distributed, constitutes
      an approximation, especially at low signal-to-noise ratios (SNRs). Based on this
      fact, previous work has argued that Rice-based activation tests show superior
      performance over their Gaussian-based counterparts at low SNRs and should be
      preferred in spite of the attendant additional computational and estimation
      burden. Here, we revisit these past studies and after identifying and removing
      their underlying limiting assumptions and approximations, provide a more
      comprehensive comparison. Our experimental evaluations using ROC curve
      methodology show that tests derived using Ricean modeling are substantially
      superior over the Gaussian-based activation tests only for SNRs below 0.6, i.e
      SNR values far lower than those encountered in fMRI as currently practiced.

PMID- 29326484
TI  - New Antarctic Gravity Anomaly Grid for Enhanced Geodetic and Geophysical Studies
      in Antarctica.
AB  - Gravity surveying is challenging in Antarctica because of its hostile environment
      and inaccessibility. Nevertheless, many ground-based, airborne and shipborne
      gravity campaigns have been completed by the geophysical and geodetic communities
      since the 1980s. We present the first modern Antarctic-wide gravity data
      compilation derived from 13 million data points covering an area of 10 million
      km2, which corresponds to 73% coverage of the continent. The remove-compute
      restore technique was applied for gridding, which facilitated levelling of the
      different gravity datasets with respect to an Earth Gravity Model derived from
      satellite data alone. The resulting free-air and Bouguer gravity anomaly grids of
      10 km resolution are publicly available. These grids will enable new high
      resolution combined Earth Gravity Models to be derived and represent a major step
      forward towards solving the geodetic polar data gap problem. They provide a new
      tool to investigate continental-scale lithospheric structure and geological
      evolution of Antarctica.

PMID- 29326485
TI  - Orphan drugs: Indian perspective.

PMID- 29326486
TI  - Standardization and validation of objective structured practical examination in
      pharmacology: Our experience and lessons learned.
AB  - OBJECTIVES: The present study is an attempt to standardize and establish validity
      and reliability of objective structured practical examination (OSPE) as a tool of
      assessment in pharmacology. METHODS: The individual stations were standardized by
      establishing the blueprint of assessment, checklists for individual OSPE
      stations, and a review and revision of existing OSPE stations through intensive
      focus group discussions. Face and content validity was established by subject
      nonexperts and experts, respectively. Internal construct reliability was assessed
      using Cronbach's alpha. The scores obtained by the students during their
      formative sessional examinations were analyzed to calculate Cronbach's alpha, a
      measure of internal construct reliability and Pearson's coefficient of
      correlation was used to analyze test-retest reliability and interexaminer
      reliability. Student and faculty feedback were taken using an open-ended
      questionnaire. RESULTS: The Pearson's coefficient of correlation for inter-rater
      reliability was 0.985, P = 0.0001. The Pearson's coefficient of correlation for
      test-retest reliability was 0.967, P = 0.0001. Cronbach's alpha values for first,
      second, and third sessional examinations were 0.825, 0.724, and 0.798,
      respectively. CONCLUSION: The faculty and student feedback received was
      constructive and enabled a systematic review of the existing method and also
      served as a means to revise the existing curricula.

PMID- 29326487
TI  - Antitoxin activity of aqueous extract of Cyclea peltata root against Naja naja
      venom.
AB  - OBJECTIVES: Snakebites are a significant and severe global health problem. Till
      date, anti-snake venom serum is the only beneficial remedy existing on treating
      the snakebite victims. As antivenom was reported to induce early or late adverse
      reactions to human beings, snake venom neutralizing potential for Cyclea peltata
      root extract was tested for the present research by ex vivo and in vivo
      approaches on Naja naja toxin. MATERIALS AND METHODS: Ex vivo evaluation of venom
      toxicity and neutralization assays was carried out. The root extracts from C.
      peltata were used to evaluate the Ex vivo neutralization tests such as
      acetylcholinesterase, protease, direct hemolysis assay, phospholipase activity,
      and procoagulant activity. Gas chromatography-mass spectrometry (GC-MS) analysis
      from root extracts of C. peltata was done to investigate the bioactive compounds.
      RESULTS: The in vivo calculation of venom toxicity (LD50) of N. naja venom
      remained to be 0.301 MUg. C. peltata root extracts were efficiently deactivated
      the venom lethality, and effective dose (ED50) remained to be 7.24 mg/3LD50 of N.
      naja venom. C. peltata root extract was found effective in counteracting all the
      lethal effects of venom. GC-MS analysis of the plant extract revealed the
      presence of antivenom compounds such as tetradecanoic and octadecadienoic acid
      which have neutralizing properties on N. naja venom. CONCLUSION: The result from
      the ex vivo and in vivo analysis indicates that C. peltata plant root extract
      possesses significant compounds such as tetradecanoic acid hexadecanoic acid,
      heptadecanoic acid, and octadecadienoic acid which can counteract the toxins
      present in N. naja.

PMID- 29326488
TI  - Resveratrol prevents liver fibrosis via two possible pathways: Modulation of
      alpha fetoprotein transcriptional levels and normalization of protein kinase C
      responses.
AB  - OBJECTIVE: Liver fibrosis is a global health problem that causes approximately
      1.4 million deaths per year. It is associated with inflammation, oxidative
      stress, necrosis and ends with cirrhosis, liver cancer, or liver failure.
      Therefore, the present study was constructed to investigate the protective effect
      of resveratrol (RVT) on liver fibrosis, focusing on the possible involvement of
      alpha 1-fetoprotein and protein kinase C signaling. MATERIALS AND METHODS: Rats
      received thioacetamide (TAA) (200 mg/kg, intraperitoneal) twice weekly, for 4
      successive weeks to induce liver fibrosis. RVT (30 mg/kg, per os) and vehicle
      were administered orally for 1 month before and another month during TAA
      intoxication. Body weights and mortality rate were assessed during the
      experiment. Liver functions and protein concentration were determined in serum,
      while liver tissues were analyzed for oxidative and fibrotic biomarkers.
      Moreover, histological examinations were performed to liver biopsies. RESULTS:
      RVT prevented the debility of TAA; liver functions including alanine
      aminotransferase, aspartate aminotransferase, bilirubin, and albumin were also
      protected. RVT prevented TAA oxidative stress, and normal liver contents of
      malondialdehyde and reduced glutathione were markedly preserved. In addition, RVT
      abolished the stimulant effect of TAA to fibrosis markers and conserved normal
      liver contents of nuclear factor kappa B, hydroxyproline, and alpha fetoprotein.
      Histological examinations indicated normal liver architecture in RVT-administered
      rats as compared to their TAA-administered peers. CONCLUSION: RVT was able to
      enhance liver functions, prevent oxidative stress, and eliminate liver fibrosis.
      Hence, the present data highlight the therapeutic potential of RVT as a
      protective agent against liver fibrosis.

PMID- 29326489
TI  - Ondansetron ameliorates depression associated with obesity in high-fat diet fed
      experimental mice: An investigation-based on the behavioral, biochemical, and
      molecular approach.
AB  - INTRODUCTION: Obesity is an important risk factor for depression as more than
      half of the obese population is susceptible for depression at double rate. Our
      earlier studies reported the antidepressant potential of 5-HT3 receptor
      antagonist, ondansetron (OND) in depression associated obesity using behavioral
      tasks. The present research work is aimed to evaluate the effect of OND on
      depression associated with obesity with special emphasis on biochemical and
      molecular mechanisms such as hippocampal brain-derived neurotrophic factor
      (BDNF), cyclic adenosine monophosphate (cAMP), 5-hydroxytryptamine (5-HT),
      hippocampal histological examination and immunohistochemical expression of p53
      proteins. MATERIALS AND METHODS: Mice were fed with high-fat diet (HFD) for 14
      weeks, followed by treatment schedule for 28 days with vehicle/OND (0.5 and 1
      mg/kg, p.o.)/reference antidepressant escitalopram (10 mg/kg, p.o.).
      Subsequently, animals were screened in the behavioral tests of depression such as
      forced swim test (FST) and sucrose preference test (SPT), biochemical estimations
      including hippocampal cAMP, BDNF and 5-HT, and molecular assays mainly histology
      and p53 expression of dentate gyrus (DG). RESULTS: HFD-fed mice showed increased
      immobility time in FST, reduced sucrose consumption in SPT, decreased level of
      signal transduction factor cAMP, neuronal growth factor BDNF and neurotransmitter
      5-HT in the hippocampus, and raised and p53 expression neuronal damage in the DG
      region of mice fed with HFD in comparison to the mice fed with normal pellet
      diet. Chronic treatment with OND (0.5 and 1 mg/kg, p.o.) significantly inhibited
      the behavioral, biochemical and molecular modifications in HFD-fed mice.
      CONCLUSION: In the preliminary study, OND attenuated depression associated with
      obesity in mice fed with HFD using various assays procedures, at least in part by
      the modulation of serotonergic transmission.

PMID- 29326490
TI  - Investigation of in vitro absorption, distribution, metabolism, and excretion and
      in vivo pharmacokinetics of paromomycin: Influence on oral bioavailability.
AB  - OBJECTIVE: The objective of this study is to investigate in vitro Caco2
      permeability, metabolism and in vivo pharmacokinetic (PK) properties of
      paromomycin to develop an efficient dosage form with improved oral
      bioavailability. MATERIALS AND METHODS: For the purpose, Caco2 permeability
      assay, mouse microsomal stability assay and in vivo PKs in male BALB/c mice were
      performed. RESULTS: In Caco-2 permeability assay, paromomycin showed negligible
      permeability in the apical to basolateral (A-to-B) direction and vice versa (B-to
      A). Marginal increase in permeability with the use of P-glycoprotein (P-gp)
      inhibitor, namely, verapamil suggesting paromomycin could be a P-gp substrate.
      Paromomycin was unstable in liver microsomes of mouse. Paromomycin showed good PK
      properties after intravenous dose in male BALB/c mice which included low plasma
      clearance, i.e., <10% of hepatic blood flow in mice, high volume of distribution
      (Vd), and half-life (T1/2) of 2.6 h. Following per oral dose, it exhibits low
      oral bioavailability (0.3%) with carboxymethyl cellulose formulation. Oral plasma
      exposure increased in mice by 10% and 15% after pretreatment with P-gp inhibitor
      verapamil and CYP inhibitor 1-Aminobenztriazole, respectively. CONCLUSION:
      Comparatively significant increase in oral plasma exposure of paromomycin was
      observed with an alternative oral formulation approach, use of P-gp and CYP
      inhibitors resulting in improved oral bioavailability up to 16%.

PMID- 29326491
TI  - Comparison of midazolam with fentanyl-midazolam combination during flexible
      bronchoscopy: A randomized, double-blind, placebo-controlled study.
AB  - BACKGROUND: Sedation during flexible bronchoscopy is desirable, but the drugs and
      the dosage protocols that are used vary. OBJECTIVE: To study and compare the
      effects of midazolam with fentanyl-midazolam combination during flexible
      bronchoscopy. MATERIALS AND METHODS: The study was conducted on 144 patients,
      from October 2013 to July 2015. They answered Hospital Anxiety and Depression
      Scale-Anxiety subscale and a prebronchoscopy questionnaire to assess their
      expectation toward flexible bronchoscopy. The patients were randomized into three
      groups: placebo, midazolam, and fentanyl-midazolam. Vitals signs including heart
      rate, respiratory rate, blood pressure, and oxygen saturation (SpO2) were
      recorded. Furthermore, Ramsay Sedation Scale was assessed during the procedure.
      Primary outcome measure was the composite score of patient-reported tolerance and
      satisfaction (assessed after the procedure). Secondary outcome measures were
      composite score of physician-reported feasibility of the procedure, hemodynamic
      changes during bronchoscopy, and side effects. RESULTS: Patient-reported
      tolerance and satisfaction composite scores (median, interquartile range) for
      placebo, midazolam, and fentanyl-midazolam groups were 54 (52, 57), 59 (57,
      61.5), 62 (58.5, 66), respectively; P < 0.001. Physician-reported feasibility
      composite scores (median, interquartile range) for the respective groups were
      24.5 (20.5, 28), 25 (21, 27), 26 (25, 29); P = 0.004. There was no significant
      difference between the groups so far as mean heart rate (P = 0.305), mean
      systolic blood pressure (P = 0.532), mean diastolic blood pressure (P = 0.516),
      mean respiratory rate (P = 0.131), and mean SpO2 (P = 0.968) were concerned.
      CONCLUSION: Conscious sedation with fentanyl and midazolam combination can result
      in better patient and operator satisfaction when compared with midazolam alone.

PMID- 29326492
TI  - Hemorheological effects of amlodipine in spontaneously hypertensive rats.
AB  - OBJECTIVES: The effect of course administration of amlodipine on whole blood
      viscosity and on macro- and microrheological parameters was evaluated. MATERIALS
      AND METHODS: SHRs were treated intragastrically with amlodipine at a dose of 10
      mg/kg for 6 weeks. After finishing the course, hemodynamic and hemorheological
      parameters were measured. RESULTS: The antihypertensive treatment with amlodipine
      resulted in a significant decrease in mean blood pressure by 29% and left
      ventricular to body weight mass index by 7%. Nevertheless, BV tended to increase.
      The administration of amlodipine had no effect on PV, plasma fibrinogen
      concentration, RBC aggregation, and RBC deformability, but hematocrit was higher
      (by 6%) than it was in control group. CONCLUSIONS: These results demonstrate that
      amlodipine has no positive hemorheological improvements when administered to
      SHRs.

PMID- 29326494
TI  - Experience of an academic institute in importing a novel preclinical drug into
      India.
AB  - The article throws light on the process of importing a novel preclinical drug
      into India based on the real-life experience from one of our studies. A novel
      drug "X" acting through a new mechanism of action was hypothesized by us to
      function as a neuroprotectant. It was decided to import this novel drug from a
      university located in Brazil. An official collaboration pact was exchanged
      between both the sides. In accordance with the Indian Drug and Cosmetics Act
      1940, unauthorized import of drug into India is not permitted. Hence, we decided
      to apply for the import license from Government of India. During the process of
      registration, we realized that the CDSCO SUGAM portal did not have facilities for
      the application from academic institute. We further faced challenges in different
      steps of import such as registration of the institute, individual drug
      application, fee transaction through the bank for Form 12, and customs duty
      clearance in the New Delhi airport. The process of import of drug for the purpose
      of testing by academic institutes has not been regularized by the CDSCO, and we
      suggest the apex organization to make separate provision for the academic
      institutes. This will encourage more academic institutes in India to opt for
      global collaborative works. This narration will further help them in following
      the same footsteps without facing significant hurdles. If more research on novel
      chemical entities is carried out in various academic institutes of India, it
      would not be far that we discover a blockbuster drug making the whole world turn
      toward us.

PMID- 29326493
TI  - Renal mitochondria can withstand hypoxic/ischemic injury secondary to renal
      failure in uremic rats pretreated with sodium thiosulfate.
AB  - BACKGROUND: Sodium thiosulfate (STS) is a potent drug used to treat calcific
      uremic arteriopathy in dialysis patients and its mode of action is envisaged by
      calcium chelation and antioxidant potential. STS's action on mitochondrial
      dysfunction, one of the major players in the pathology of vascular calcification
      is yet to be explored. METHODS: Adenine (0.75%, 28 days)-treated vascular
      calcified rat kidney was used to isolate mitochondria, where the animal was
      administered with or without STS for 28 days. Isolated mitochondria were
      subjected to physiological oxidative stress by nitrogen gas purging
      (hypoxia/ischemia-reperfusion injury) to assess mitochondrial recovery extent due
      to STS treatment in vascular calcified rat kidney. RESULTS: The results confirmed
      an elevated oxidative stress and deteriorated mitochondrial enzyme activities in
      all groups except the drug-treated group. CONCLUSION: The STS treatment, besides
      rendering renal protection against adenine-induced renal failure, also helped to
      maintain mitochondrial functional integrity in a later insult due to
      hypoxia/ischemia-reperfusion injury.

PMID- 29326495
TI  - Acute dystonic reaction leading to lingual hematoma mimicking angioedema.
AB  - Lingual hematoma is a severe situation, which is rare and endangers the airway.
      It can develop due to trauma, vascular abnormalities, and coagulopathy. Due to
      its sudden development, it can be clinically confused with angioedema. In
      patients who applied to the doctor with complaints of a swollen tongue, lingual
      hematoma can be confused with angioedema, in particular, at the beginning if the
      symptoms occurred after drug use. It should especially be considered that
      dystonia in the jaw can present as drug-induced hyperkinetic movement disorder.
      Early recognition of this rare clinical condition and taking precautions for
      providing airway patency are essential. In this case report, we will discuss
      mimicking angioedema and caused by a bite due to dystonia and separation of the
      tongue from the base of the mouth developing concurrently with lingual hematoma.

PMID- 29326496
TI  - A Simple Method for Deriving the Confidence Regions for the Penalized Cox's Model
      via the Minimand Perturbation.
AB  - We propose a minimand perturbation method to derive the confidence regions for
      the regularized estimators for the Cox's proportional hazards model. Although the
      regularized estimation procedure produces a more stable point estimate, it
      remains challenging to provide an interval estimator or an analytic variance
      estimator for the associated point estimate. Based on the sandwich formula, the
      current variance estimator provides a simple approximation, but its finite sample
      performance is not entirely satisfactory. Besides, the sandwich formula can only
      provide variance estimates for the non-zero coefficients. In this article, we
      present a generic description for the perturbation method and then introduce a
      computation algorithm using the adaptive least absolute shrinkage and selection
      operator (LASSO) penalty. Through simulation studies, we demonstrate that our
      method can better approximate the limiting distribution of the adaptive LASSO
      estimator and produces more accurate inference compared with the sandwich
      formula. The simulation results also indicate the possibility of extending the
      applications to the adaptive elastic-net penalty. We further demonstrate our
      method using data from a phase III clinical trial in prostate cancer.

PMID- 29326498
TI  - Secret Weapon in the Battle Against Cavities?

PMID- 29326497
TI  - Is the modified Harris hip score valid and responsive instrument for outcome
      assessment in the Indian population with pertrochanteric fractures?
AB  - Introduction: The original Harris hip score (HHS) does not contain ability to
      perform squatting and sitting cross legged as items in the questionnaire and
      hence a need was felt to modify the Harris hip score so that it could stay
      relevant in functional assessment of Indian patients in the rural setting.
      Validity, responsiveness and ceiling floor effect of the Harris hip score after
      internal fixation of pertrochanteric fracture has not been previously described.
      The objective of the study was to investigate construct validity, responsiveness
      and ceiling floor effects of the modified Harris hip score (mHHS). Methods: For
      evaluation of construct validity two hypotheses were formulated: first, there
      would be no difference in mHHS in cohort of patients treated with short or long
      proximal femoral nail and second, patients younger than 65 years will have higher
      mHHS compared to patients older than 65 years postoperatively. Proportion of
      patients obtaining lowest score of 0 point (floor effect) and those obtaining
      highest score of 100 points (ceiling effect) was evaluated at one, three and six
      months postoperatively. It is recommended that the proportion of ceiling and
      floor effect should be lower than 15% in order to deduce satisfactory internal
      and content validity of an outcome instrument. Responsiveness was evaluated using
      distribution based methods (effect size and standardised response mean) and
      anchor based method (area under the curve using receiver operating curve).
      Ability to perform cross leg sitting and squatting at six months postoperatively
      were chosen as two different external anchors. Effect size and standardised
      response mean values higher than 0.80 and area under the curve value higher than
      0.70 are indicators of adequate responsiveness of an outcome instrument. Results:
      Eighty one consecutive patients with pertrochanteric hip fractures and treated
      with long and short proximal femoral nail were included in this prospective
      observational study. Six patients were lost to follow-up due to mortality and
      complete functional outcome data was available in 75 patients (92.6%). The mean
      age was 68 years (range: 38-89 years). The mHHS at one, three and six months
      postoperatively was 39.9 +/- 9.5, 61.6 +/- 14.7 and 81.0 +/- 15.9 respectively.
      The improvement in mHHS was significant at all time intervals. In accordance with
      the hypothesis, there was no significant difference in mHHS at one, three and six
      months postoperatively in patients treated with short or long proximal femoral
      nail. In accordance with the hypothesis, patients younger than 65 years had
      significantly better mHHS at one, three and six months postoperatively as
      compared to patients older than 65 years. There were no floor or ceiling effects
      at one, three and six months postoperatively. mHHS showed adequate internal
      responsiveness (Effect size = 4.34; standardised response mean = 4.26) and
      adequate external responsiveness (Area under curve = 0.77 and 0.89) using
      different external anchors. Conclusion: The mHHS has adequate construct validity,
      internal validity and responsiveness to evaluate functional outcome of
      intramedullary nail fixation in pertrochanteric hip fractures in the Indian
      population.

PMID- 29326499
TI  - In Search of a Novel Substitute: Clinical and Radiological Success of Lesion
      Sterilization and Tissue Repair with Modified 3Mix-MP Antibiotic Paste and
      Conventional Pulpectomy for Primary Molars with Pulp Involvement with 18 Months
      Follow-up.
AB  - Objectives: The aim of this study was to evaluate the clinical and radiographic
      success of zinc oxide (ZnO)-ozonated oil, modified 3Mix antibiotic paste, and
      vitapex in the treatment of primary molars requiring pulpectomy. Methods: Sixty
      four primary molars of forty-three healthy children aged between 4 and 8 years
      with primary molars requiring root canal procedure were treated with ZnO-ozonated
      oil, modified 3Mix-MP antibiotic paste, and vitapex. Clinical follow up was done
      at 1, 6,12 months and 18 months while radiographical follow-up was done at 6,12
      and 18 months, respectively. Results: The results showed that the clinical
      success rates of ZnO-ozonated oil, modified 3Mix-MP paste and vitapex were
      95.5%,89.5% and 100% respectively and radiographical success rates were
      94.4%,80.95% and 100% respectively after 18 months period of observation.
      Conclusion: The overall success rates of ZnO-ozonated oil, vitapex and modified
      3Mix antibiotic paste were comparable.

PMID- 29326500
TI  - A Comparative Evaluation between Cheiloscopic Patterns and Terminal Planes in
      Primary Dentition.
AB  - Objective: To assess the correlation between different cheiloscopic patterns with
      the terminal planes in deciduous dentition. Materials and Methods: Three hundred
      children who are 3-6 years old with complete primary dentition were recruited,
      and the pattern of molar terminal plane was recorded in the pro forma. Lip prints
      of these children were recorded with lipstick-cellophane method, and the middle
      10 mm of lower lip was analyzed for the lip print pattern as suggested by
      Sivapathasundharam et al. The pattern was classified based on Tsuchihashi and
      Suzuki classification. Results: Type II (branched) pattern was the most
      predominant cheiloscopic pattern. The predominant patterns which related to the
      terminal planes were as follows: Type IV (reticular) and Type V (irregular)
      pattern for mesial step, Type IV (reticular) pattern for distal step, and Type I
      (complete vertical) pattern for flush terminal plane. No significant relationship
      was obtained on gender comparison. Conclusion: Lip prints can provide an
      alternative to dermatoglyphics to predict the terminal plane in primary
      dentition. Further studies with larger sample size are required to provide an
      insight into its significant correlations.

PMID- 29326501
TI  - Analysis of Salivary IgA, Amylase, Lactoferrin, and Lysozyme Before and After
      Comprehensive Dental Treatment in Children: A Prospective Study.
AB  - Objective: This study aimed to evaluate the levels of salivary IgA, amylase,
      lactoferrin, and lysozyme before and after comprehensive dental treatment in
      children with early childhood caries. Design: Thirty children aged 36-60 months,
      with a deft score >=5, were selected for the study. Before dental treatment,
      paraffin-stimulated whole saliva was collected in a sterile graduated cup for a
      period of 5 min. The saliva samples were quantitatively analyzed for levels of
      IgA, amylase, lactoferrin, and lysozyme using enzyme-linked immunosorbent assay.
      Comprehensive dental treatment was carried out in all the children including
      caries preventive procedures. A second sample of saliva was collected at 3 months
      following completion of dental treatment. Data obtained was subjected to
      statistical analysis using Student's t-test. Results: The mean levels of salivary
      IgA was significantly reduced from 59.60 MUg/ml to 56.42 MUg/ml after dental
      treatment (P < 0.05). There was a significant reduction in the levels of salivary
      amylase from 115.78 MUg/ml to 113.33 MUg/ml (P < 0.001). Following dental
      treatment, salivary lactoferrin and lysozyme levels were significantly reduced
      from 3.76 MUg/ml and 10.62 MUg/ml to 3.44 MUg/ml and 10.27 MUg/ml, respectively
      (P < 0.001). Conclusions: Levels of salivary IgA, amylase, lactoferrin, and
      lysozyme were reduced significantly at 3 months following comprehensive dental
      treatment.

PMID- 29326502
TI  - Comparative Evaluation of Platelet-Rich Fibrin with Connective Tissue Grafts in
      the Treatment of Miller's Class I Gingival Recessions.
AB  - Background: One of the most common aesthetic problem encountered in the field of
      periodontology is gingival recession, which is, perceived by the patients as
      increase in length of teeth. The treatment of buccal gingival recession is a
      common requirement due to aesthetic concern or root sensitivity. This study was
      planned to evaluate the efficacy of PRF membrane compared to that of CTG in
      Miller's class I gingival recessions. Materials and Methods: 32 sites with
      Miller's Class I gingival recessions, out of which 16 sites received PRF (test)
      and 16 sites received CTG (control). Each patient had undergone an initial
      periodontal treatment, including oral hygiene instructions, plaque control, and
      scaling and root planing, followed by re-evaluation. All clinical recordings;
      recession height, recession width, clinical attachment level, height of
      keratinized tissue, thickness of keratinized tissue, healing index and pain
      perception, were performed immediately before surgery (baseline) and after 6
      months interval following periodontal surgery. Results: In the test group,
      significant improvement was seen in terms CAL, REC-HT, REC-WD, HKT and TKT from
      baseline to 6 months. In the control group, only significant improvement seen was
      in REC-HT and TKT from baseline to 6 months. Comparison of both Healing Index and
      VAS score was done and it showed no significant difference between test and the
      control group except VAS at 1 week. Conclusion: Though CTG is a gold standard
      procedure, PRF can be used as an alternative procedure by keeping patient's
      comfort and recognition in mind.

PMID- 29326503
TI  - Impact of Dental Trauma on Quality of Life Among 11-14 Years Schoolchildren.
AB  - Background: Traumatic injuries are common dental problems in pediatric dentistry
      that may influence the children's quality of life. Aim: the aim of this study is
      to assess the impact of traumatic dental injuries (TDI) and oral health-related
      quality of life (OHRQoL) among Egyptian schoolchildren aged 11-14 years.
      Materials and Methods: A cross-sectional study was carried out involving a sample
      of 11700 schoolchildren from public and private schools of Mansoura city, Egypt.
      OHRQoL was assessed using Child Perceptions Questionnaire. Clinical examination
      included the presence and type of TDI, malocclusion status, and dental caries in
      anterior teeth (decayed, missing, and filled teeth). Results: The prevalence of
      TDI was 13.6%. Untreated TDI was more likely to have a negative impact on the
      children's daily living regarding pain, functional, emotional, and social aspect
      than treated injuries and control children. Pearson's correlation test indicated
      significant association between trauma and malocclusion and dental caries.
      Conclusion: Untreated dental injury has a negative impact on quality of life
      regarding social, functional, and emotional aspects. However, treated injured
      teeth appear to improve social and emotional aspects of the OHRQoL of school
      children, whereas functional limitations may continue because of the pulpal and
      periodontal effects of the injury.

PMID- 29326505
TI  - Influence of Intracanal Irrigants on Coronal Fracture Resistance of
      Endodontically Treated and Bleached Teeth: An In vitro Study.
AB  - Background: Irrigation has a key role in the success of endodontic treatment.
      Intracanal irrigant solutions have adverse effects on the physical properties of
      dentin. Aim: The present study aimed to evaluate the effect of different
      irrigation protocols on coronal fracture resistance of endodontically treated
      teeth undergoing bleaching treatment. Design and Materials and Methods: Access
      cavities were prepared in 120 maxillary premolars which were divided into two
      groups (n = 60) - Group A: nonbleached, Group B: bleached (B). Each group was
      subdivided into five subgroups based on irrigation protocol (n = 12); G1: normal
      saline (NS), G2: 2.5% sodium hypochlorite (NaOCl), G3: 10% citric acid (CA), G4:
      17% ethylene diamine tetra acetic acid, and G5: NaOCl plus CA. In Group B, the
      teeth were bleached using 38% hydrogen peroxide and 20% carbamide peroxide gels
      as in-office and at-home bleaching techniques for 3 weeks. All the teeth were
      restored with composite resin, thermocycled, and incubated for 24 h. The
      specimens underwent fracture resistance tests. Data were analyzed with ANOVA,
      Tukey honestly significant difference test, t-test, and Chi-squared test (alpha
      =0.05). Results: T-test showed significant differences between each two
      corresponding subgroups (P < 0.0001). In Group A, NS demonstrated significantly
      higher fracture resistance compared to others; however, minimum fracture
      resistance recorded in G2. In Group B, the maximum fracture resistance was
      recorded in G1, with the minimum being recorded in G5. Samples irrigated with
      NaOCl and NaOCl plus CA exhibited significantly lower fracture resistance
      compared to NS subgroup (P < 0.05). Conclusions: Within the limitations of this
      study, it can be concluded that the irrigation protocol used during endodontic
      treatment with/without bleaching can affect the coronal fracture resistance.

PMID- 29326504
TI  - Oral Health-Related Quality of Life Following Third Molar Surgery in an African
      Population.
AB  - Introduction: Surgical extraction of impacted mandibular third molars is often
      associated with sequelae such as postoperative pain, facial edema, and limitation
      in mouth opening ability. These sequelae may result in changes in the patients'
      lifestyle and quality of life (QoL). Aim: The aim of this study was to evaluate
      the effect of surgical extraction of impacted mandibular third molars on
      patients' QoL in the immediate postoperative period (7 days). Materials and
      Methods: Ethical approval for this study was obtained from the Health Research
      and Ethics committee of the Lagos University Teaching Hospital. A total of 124
      individuals with impacted mandibular third molars, who satisfied the inclusion
      criteria and consented to participate in this study, were included. The Oral
      Health Impact Profile-14 (OHIP-14) QoL questionnaire was used to assess QoL. QoL
      was assessed preoperatively (baseline) and on postoperative days (PODs) 1, 3, and
      7. Maximal interincisal mouth opening, facial width, and pain were also reviewed
      at all evaluation points. Data analysis was done using the Statistical Package
      for Social Sciences (SPSS) for Windows (version 16.0, Chicago, IL, USA). Results:
      A total of 124 individuals were included in the final analysis. An age range of
      18-51 years with a mean (+/-standard deviation) of 28.5 (7.4) years was observed.
      A male to female ratio of 1:1.5 was observed. The most frequently encountered
      type of impaction was the mesioangular impaction 51 (41.1%) and recurrent
      pericoronitis was the principal reason for extraction 53 (42.7%). The severity of
      the sequelae (pain, trismus, and facial edema) was maximal on the first POD.
      Patients' overall QoL deteriorated sharply on the first POD and subsequently
      improved. Conclusion: Surgical extraction of mandibular third molars is
      associated with worsening of patients' postoperative QoL in the immediate
      postoperative period. Prospective patients should be informed about this, and
      ways of reducing this untoward effect should be explored.

PMID- 29326506
TI  - The Bond Strength of Nanohybrid and Nanoceramic Composites to Feldspathic
      Porcelain.
AB  - Background: Porcelain fracture is the most important problem in fixed prosthetic
      restorations. The replacement of fractured restoraions isn't often prefer by
      patients and dentists. Intraoral repair of fractured porcelain is a big
      alternative for patient and dentist. For this reason, dentists try to improve
      different surface treatments to increase the bond strength between porcelain and
      repair materials such as composite resins. Aims: The aim of this study was to
      evaluate the shear bond strength (SBS) of nano-hybrid (Nh.com) and nano-ceramic
      composite resins (Nc.com) to this feldspathic porcelains (Vita and Ivoclar).
      Settings and Design: 120 ceramic disc were fabricated from feldspathic porcelain.
      Materials and Methods: The following surface treatment was applied on the ceramic
      surface: 1) Hydrofluoric acid+silane, 2) Air-abrasion+silane, 3) Air
      abrasion=Control group. Nh.com and Nc.com was placed on the porcelain surface.
      Half of the specimens were stored in 37 +/- 2oC distilled water and another half
      were subjected to thermocycling before SBS. The samples placed in an universal
      testing machine and applied shear force until seperation occured. Statistical
      Analysis Used: The data were analyzed by multi-way analysis of variance (ANOVA)
      and Duncan test (P <0.05). Results: The results show that Ivoclar and Vita had
      almost equal fracture values. Nh.com showed high bond strength than Nc.com. In
      the Ivoclar porcelain, hydrofluoric acid etching had highest fracture values than
      other surface treatments, and in the vita porcelain air-abrasion had a little
      difference from hydrofluoric acid etching. Conclusions: Different surface
      treatments show different effect on SBS between feldspathic porcelain and
      composite resins.

PMID- 29326507
TI  - Effect of Calcium Channel Blockers on Gingival Tissues in Hypertensive Patients
      in Lagos, Nigeria: A Pilot Study.
AB  - Background: Long-term treatment of common chronic cardiac conditions such as
      hypertension with calcium channel blockers (CCBs) has long been associated with
      gingival hyperplasia. This oral side effect may affect esthetics and function,
      yet often overlooked and therefore underreported among Nigerians. Aim: This study
      aimed to determine the association of CCBs with gingival overgrowth (GO) in
      hypertensive patients. Methods: This was a hospital-based, case-control study
      conducted among 116 hypertensive patients (58 CCB and 58 non-CCB age-matched
      controls) attending the medical outpatient clinic of a tertiary health
      institution in Lagos, Nigeria. Data collection tools included interviewer
      administered questionnaires and periodontal examination. Sociodemographic
      details, medical history, and periodontal indices (gingival index, plaque index,
      class of GO according to drug-induced GO [DIGO] Clinical Index) were recorded.
      Results: The mean age was 59.4 +/- 12.6 years, females representing 50.9%. In the
      CCB group, 39 (67.2%) participants were on amlodipine and 19 (32.8%) were on
      nifedipine. The mean duration of CCB use was 55.6 +/- 53 months. DIGO was higher
      in CCB (36.2%) than that in non-CCB participants (17.2%) (chi2 = 4.4, P = 0.036).
      The risk of GO was higher in CCB users (odds ratio [OR] 2.7, [95% confidence
      interval (CI)]: 1.1-6.5). Amlodipine users had higher DIGO (37.5%) than that of
      nifedipine users (21.1%) (OR 2.3, [95% CI]: 1.0-5.3). The predominant class of
      DIGO among the CCB users was Class 2 DIGO Clinical Index (90.5%). Conclusion: The
      study reveals that the risk of GO is nearly three times in CCB than that of non
      CCB users and twice higher in amlodipine than nifedipine users in Nigeria.

PMID- 29326508
TI  - Effect of Ultraviolet Irradiation on the Osseointegration of a Titanium Alloy
      with Bone.
AB  - Introduction: Attempt has been made to analyze the potential of titanium (Ti)
      alloy for osteointegration by the effect of surface photo functionalization in
      different aspects as follows: in Ringer's solution, in vitro cell growth, and in
      vivo study on rabbit. The present study was aimed to investigate the influence of
      ultraviolet (UV) light on surface topography, corrosion behavior, and bioactivity
      of indigenously manufactured samples of Ti alloy mini-implant. Materials and
      Methods: The study includes surface modification of Ti samples by UV treatment,
      corrosion testing of the specimens using Potentiostat (GAMRY System), qualitative
      examination of modified surface topography using scanning electron microscope,
      and cellular viability test on Ti alloy surface (3-(4,5-Dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide ASSAY). To find the effect of UV light on implant
      bone integration, biochemical test was performed on the femur of rabbits. Results
      and Discussion: Corrosion resistance of untreated Ti alloy in Ringer's solution
      was found to be less, whereas corrosion rate was more. Corrosion resistance of UV
      treated samples was found to increase significantly, thereby lowering the
      corrosion rate. Cell growth in UV-treated specimen was observed to be higher than
      that in untreated samples. It is important to mention that cell growth was
      significantly enhanced on samples which were UV treated for longer duration of
      time. Conclusions: There was a marked improvement in cell growth on UV-treated Ti
      alloy samples. Hence, it is expected that it would enhance the process of
      osseointegration of Ti with bone. Another important finding obtained was that the
      removal torque values of UV-treated implants were higher than that of untreated
      implants. The overall result reveals that UV treatment of implants does help us
      in speeding up the osseointegration process.

PMID- 29326509
TI  - A Radiographic Study of the Association between Apical Periodontitis and
      Technical Quality of Intraradicular Posts and Root Canal Fillings: A Cross
      sectional Study in Qassim Region, Saudi Arabia.
AB  - Objectives: This study evaluates the association between the apical periodontitis
      (AP) and quality of intraradicular posts and the quality of root fillings
      assessed radiographically in Qassim region, Saudi Arabia. Materials and Methods:
      Digital periapical radiographs of 327 teeth with post-retained restoration were
      retrieved randomly from the Qassim University screening clinic's digital archives
      and evaluated. The quality of the intraradicular post and root filling was
      evaluated according to the optimum criteria. The presence of AP was assessed
      based on the periapical index scoring system. The relation between the post
      technical quality, the quality of root filling, and AP was determined. The data
      were analyzed using Chi-square test and logistic regression. Results: AP was
      found in 22% of the investigated teeth. Adequate root fillings were found in 69%
      of roots, and 14% of these cases were associated with AP. In roots with root
      filling classified as inadequate, 38% had AP with a statistically significant
      association between the root filling length and the presence of AP (P < 0.001).
      The most frequently used posts were prefabricated metallic posts (57%). Teeth
      restored with cast posts and prefabricated metallic posts exhibited AP with a
      frequency of 42.3% and 25.4%, respectively, and teeth with nonmetallic posts had
      significantly fewer cases of AP (12.0%) with a statistically significant
      association between the post type and the presence of AP (P = 0.016). Conclusion:
      Both the quality of the root filling and the intraradicular post type were
      correlated significantly with the presence of AP. The technical quality of root
      fillings and intraradicular posts was adequate. Nevertheless, the use of threaded
      posts is still a common practice in this study population.

PMID- 29326510
TI  - Isolation and Typing of Streptococcus mutans and Streptococcus sobrinus from
      Caries-active Subjects.
AB  - Background: Streptococcus mutans and Streptococcus sobrinus are main etiological
      agents of dental caries. Aim: The aim of the study was to isolate, identify,
      characterize, and determine the minimum inhibitory concentration (MIC) of S.
      mutans and S. sobrinus from caries-active subjects. Materials and Methods: Sixty
      five plaque samples were collected from caries-active subjects aged between 35
      and 44 years, processed and cultured on mitis salivarius bacitracin agar. All the
      bacterial isolates were subjected to morphotyping and the suspected colonies were
      identified by 16S rDNA sequencing. The S. mutans and S. sobrinus strains were
      characterized by biotyping and phylogenetic analysis. The MIC of ampicillin and
      erythromycin was determined by microtiter plate method. Results: Of the study
      population, 41 isolates displayed typical colony morphologies of S. mutans and S.
      sobrinus. The 16S rDNA sequencing results revealed that 36 isolates were S.
      mutans and 5 isolates were S. sobrinus. The biotyping of these isolates
      demonstrated three biotypes, namely, biotype I (n = 35), biotype III (n = 1), and
      biotype IV (n = 2). However, 3 isolates exhibited variant biotypes. The
      phylogenetic analysis revealed that the clinical strains of S. mutans and S.
      sobrinus clustered independently along with respective reference strains. The
      average MIC of ampicillin and erythromycin against S. mutans and S. sobrinus was
      0.047 MUg/ml and 0.39 MUg/ml, respectively. Conclusion: The 16S rDNA sequencing
      was an impeccable method for S. mutans and S. sobrinus identification when
      compared with morphotyping and biotyping methods. The study also suggested that
      nonspecific bacteria might be involved in caries formation.

PMID- 29326511
TI  - Differential Diagnosis between Chronic versus Aggressive Periodontitis and
      Staging of Aggressive Periodontitis: A Cross-sectional Study.
AB  - Background: Differentiating between chronic periodontitis (CP) and aggressive
      periodontitis (AgP) is challenging. The aim of this study was to assess the
      variations in diagnosis between CP versus AgP and the staging of AgP based on the
      disease-staging index for AgP among periodontists, specialists in oral medicine,
      and general dental practitioners (GDPs). Materials and Methods: Fifteen cases
      diagnosed as either CP or AgP were included in a "case document" and sent
      electronically to 75 respondents. Case document included a detailed history with
      periodontal charting, clinical features, images, and radiographs for all the
      cases. Diagnosis and staging for the case (if diagnosed as AgP) were requested. A
      reordered case document (cases in a different sequence) was again sent to
      respondents after a gap of 1 month. Statistical analysis: Descriptive statistics
      including frequency and percentage were calculated. Pearson's Chi-square test was
      used to analyze the data collected. Results: For the "case document," 10.17% of
      the responses were different from those of the authors for diagnosis, whereas
      4.48% of the responses were different from those of the authors for the staging
      of AgP. The agreement in the overall responses was in the range of 0.69-0.84,
      which was considered good. Comparison of the responses for diagnosis showed
      statistically significant (P = 0.009) difference between specialists in oral
      medicine and GDPs. Conclusions: Variations exist among respondents regarding the
      diagnosis of CP versus AgP. Staging of AgP based on the listed criteria showed
      low variations.

PMID- 29326512
TI  - Evaluating the Effect of Different Conditioning Agents on the Shear Bond Strength
      of Resin-Modified Glass Ionomers.
AB  - Aim of the Study: This study aims to evaluate the effects three different
      conditioning agents on the shear bond strength of resin-modified glass ionomers
      to human dentin. Materials and Methods: One hundred and twenty recently
      extracted, caries-free premolars and molars will be cleaned of debris and
      disinfected in a 0.5% solution of sodium hypochlorite and sterile water for 30
      min. The occlusal surface of each tooth will be reduced using conventional model
      trimmer with water to produce the dentin surface. Then, three different resin
      modified glass ionomer cements (GICs) were triturated and mixed according to the
      manufacturer's instructions, 10 specimens will be made of each group. The excess
      restorative material will be removed from matrix band dentin interface with a
      sharp number 25 bard parker blade. Samples were shear tested with Instron
      universal testing machine with a crosshead speed of 0.5 mm/min. A shearing bar
      beveled to a 1 mm thick contact surface area will be placed at the junction of
      dentin and plastic band matrix. The load required for the failure will be
      recorded in pounds and converted to megapascals. Results: Statistical analysis
      was done with analysis of variance and Tukey's test. Ketac primer as conditioning
      agent along with Fuji II LC as restorative material had the highest shear bond
      value whereas intact smear layer which was unmodified dentin had the least value.
      Conclusion: Within the limitations of the present study, it can be concluded that
      surface conditioning of dentin resulted significantly higher bond strength than
      unconditioned dentin surfaces. Clinical Significance: Resin-modified glass
      ionomers have several advantages compared to chemically cured GICs. The
      advantages include command cure, ease of handling, improved physical properties,
      and esthetics. Resin.modified glass ionomers have been marketed as direct
      restorative materials for Class V lesions as well as liners, bases, and luting
      agents. Several conditioning agents have been evaluated to condition dentin
      before the application of conventional glass ionomers and resin-modified glass
      ionomers. These have mainly included polyacrylic acid, citric acid, phosphoric
      acid, and ethylenediamine tetra.acetic acid. Of late, manufactures have
      recommended other conditioners to replace polyacrylic acid which includes Ketac
      primer as one of the conditioning agents.

PMID- 29326513
TI  - An In vitro Comparison of Pushout Bond Strength of Resilon with MetaSEAL and AH
      Plus Sealers.
AB  - Aim: The aim of this study is to evaluate and compare the pushout bond strengths
      of Resilon with two different sealers: Resilon/MetaSEAL (methacrylate based) and
      Resilon/AH Plus (an epoxy resin-based sealer). Materials and Methods: Forty
      single canal anterior teeth were decoronated at cementoenamel junction and
      standardized to 10 +/- 1 mm length. Working length was determined followed by
      biomechanical preparation. Then, the specimens were randomly assigned into two
      groups of 20 teeth each based on the sealer used with Resilon. All canals were
      obturated using single-cone obturation technique. Root samples were prepared for
      pushout testing. The universal testing machine gave the debonding force for
      individual specimen. This was done for all the specimens. Statistical Analysis:
      This was done by using unpaired Student's t-test. Results: The roots filled with
      Resilon/MetaSEAL had higher bond strength (1.49 +/- 0.09 MPa) compared to
      Resilon/AH Plus (0.90 +/- 0.04 MPa) group. The difference in bond strength was
      statistically significant (P = 0.0000). Conclusion: Through this pushout bond
      strength test, it could be noted that MetaSEAL did appear to bond to the dentin
      and could be used as a potential endodontic sealer.

PMID- 29326514
TI  - Modified Angle's Classification for Primary Dentition.
AB  - Aim: This study aims to propose a modification of Angle's classification for
      primary dentition and to assess its applicability in children from Central India,
      Nagpur. Methods: Modification in Angle's classification has been proposed for
      application in primary dentition. Small roman numbers i/ii/iii are used for
      primary dentition notation to represent Angle's Class I/II/III molar
      relationships as in permanent dentition, respectively. To assess applicability of
      modified Angle's classification a cross-sectional preschool 2000 children
      population from central India; 3-6 years of age residing in Nagpur metropolitan
      city of Maharashtra state were selected randomly as per the inclusion and
      exclusion criteria. Results: Majority 93.35% children were found to have
      bilateral Class i followed by 2.5% bilateral Class ii and 0.2% bilateral half
      cusp Class iii molar relationships as per the modified Angle's classification for
      primary dentition. About 3.75% children had various combinations of Class ii
      relationships and 0.2% children were having Class iii subdivision relationship.
      Conclusions: Modification of Angle's classification for application in primary
      dentition has been proposed. A cross-sectional investigation using new
      classification revealed various 6.25% Class ii and 0.4% Class iii molar
      relationships cases in preschool children population in a metropolitan city of
      Nagpur. Application of the modified Angle's classification to other population
      groups is warranted to validate its routine application in clinical pediatric
      dentistry.

PMID- 29326515
TI  - Scanning Electron Microscopic Evaluation of Efficacy of 17%
      Ethylenediaminetetraacetic Acid and Chitosan for Smear Layer Removal with
      Ultrasonics: An In vitro Study.
AB  - Introduction: The main aim of root canal treatment is cleaning, shaping and then
      obturating three dimensionally to prevent reinfection. This includes
      chemicomechanical cleansing by instrumentation and the use of irrigating
      solutions. Therefore, the purpose of this study was to compare the smear layer
      removal from root canal dentine subjected to two root canal irrigants, 17% EDTA
      and 0.2% Chitosan, a new irrigant using Scanning Electron Microscope.
      Methodology: 40 single rooted premolars were decoronated followed by
      instrumentation with I Race files and intermediate irrigation with 3% sodium
      hypochlorite and activation with ultrasonics. Then the samples were
      longitudinally sectioned and place in the respective test solutions and their
      controls for 5 minutes. Scanning Electron Microscopic evaluation was further
      carried out. Results: The results of the present study indicates that the
      Chitosan which was proved effective in removing smear layer. Conclusion: A
      moderate concentration of 0.2% chitosan removes the smear layer with greater
      efficiency.

PMID- 29326516
TI  - Indirect Sinus Lift Done Using "Autogenous Core Lift" Technique in Combination
      with Alloplastic Phosphosilicate Putty in Atrophic Maxillary Posterior Region: A
      Clinical Report with 1-Year Follow-Up.
AB  - Pneumatization of the sinus is a common occurrence after extraction of maxillary
      posterior teeth. Implant procedures require a clinically acceptable level of bone
      to be present for implants to be placed in function. Residual bone with >4 mm of
      height can be managed using the indirect sinus lift procedure, whereas bone
      height <4 mm requires a direct sinus lift using lateral window approach. This
      clinical case report describes the use of autogenous core used to lift the
      membrane in conjunction with calcium phosphosilicate putty using minimal
      armamentarium, thereby avoiding the associated morbidity and complications
      associated with a direct sinus lift procedure.

PMID- 29326517
TI  - 18p Deletion Syndrome: Case Report with Clinical Consideration and Management.
AB  - 18p deletion syndrome is characterized by the deletion of short arm of chromosome
      18. Presentation of this syndrome is quite variable with dysmorphic features,
      growth deficiencies, and mental retardation with poor verbal performance. Few
      patients even fail to thrive when malformations involving the heart and brain are
      severe. In the present article, we report an isolated case of 18p deletion in a
      23-year-old female who for the first time reported to the hospital for dental
      problems. The patient was short statured with mental retardation and
      craniofacial, skeletal, dental, and endocrinal abnormalities. Such presentation
      warrants prompt diagnosis for effective management. Furthermore, genetic
      counseling for such patients and their families should be considered as a part of
      treatment itself.

PMID- 29326518
TI  - Toothpaste Use Protocol with Dental Bleaching for a Conservative Treatment: Case
      Reports.
AB  - In-office bleaching is a treatment based on products that contain hydrogen
      peroxide (HP) while demonstrating whitening effectiveness. HP could promote
      alterations to surface morphologies and properties of dental tissues. The
      objective was describe a toothpaste protocol associated to bleaching therapy to
      promote a safer approach. Patient 1 (male) and Patient 2 (female) were attended,
      and toothbrushing (twice a day) with a dentifrice containing bioactive glass (BG)
      (NovaMinTM) and fluoride was indicated before and during the treatment. Three
      bleaching sessions were made in cases, at intervals of 7 days. The gels used were
      35% HP (Patient 1) and 35% HP supplied with calcium (Patient 2). The
      effectiveness of bleaching treatment was observed in both cases (Vita scale),
      with an esthetic self-acceptance. Sensitivity associated with the procedure was
      not reported. The indication of BG-based toothpaste is relevant in relation to
      enamel properties and did not affect the whitening effectiveness of dental
      bleaching.

PMID- 29326519
TI  - Tetanus: A Report of Two Cases and Review of Literature - A Continuing Threat to
      the Elderly in Japan.
AB  - Tetanus has become rare in industrialized countries, largely due to the
      effectiveness of immunization. However, the elderly are susceptible to tetanus
      because many have not received primary immunization; the incidence of tetanus in
      Japan is still 120 cases/year. The initial symptoms of tetanus, such as trismus
      and dysphagia, are observed in the orofacial region. However, because of the
      disease's rarity, the clinician may be unfamiliar with the clinical presentation
      and may not suspect tetanus. We report two cases of elderly patients with
      generalized tetanus. Both patients presented trismus and/or dysphagia and
      consulted three different departments before the diagnosis of tetanus. Japanese
      clinicians will encounter tetanus more frequently than practitioners in other
      countries. Dental surgeons should be familiar with the clinical appearance of
      tetanus and should consider this disease in a nonimmunized patient presenting as
      an atypical case of trismus and dysphagia.

PMID- 29326520
TI  - The So-called Garre's Osteomyelitis of Jaws and the Pivotal Utility of Computed
      Tomography Scan.
AB  - The present paper draw the attention of clinicians to investigate multiple slices
      of the computed tomography (CT) scan looking for a safe diagnosis of the so
      called Garre's osteomyelitis (GO) of jaws, a not uncommon disease characterized
      by astonishing bone growth. We report a case involving the left mandible of a 12
      year-old girl presenting with a bony enlargement at left mandible. Initial
      examination revealed carious process of tooth 36 with radiographic apical
      rarefaction. However, we need to take care with this diagnosis because other
      aggressive diseases may cause bone enlargement mimicking GO. We observed here
      that careful examination of CT slices must be elucidative. In the present case,
      we observed the formation of a hypodense channel between periapical disease and
      the bone growth, through CT, thus supporting the pathophysiologic conditions for
      GO and allowing a safer decision to make the intervention restricted to tooth.

PMID- 29326521
TI  - Surgical Management of Large Radicular Cyst Associated with Mandibular Deciduous
      Molar Using Platelet-rich Fibrin Augmentation: A Rare Case Report.
AB  - Radicular cysts arising from deciduous teeth are rare and usually cause a large
      bony defect. Autologous platelet-rich fibrin (PRF) is an easily available healing
      biomaterial in oral surgical defect with the new perspective of accelerated
      healing of a large bony defect. The present case is of unusually large radicular
      associated with neglected carious mandibular deciduous second molar in 10-year
      old girl and its surgical management with PRF augmentation as a healing
      biomaterial in the bony defect. One-year follow-up showed uneventful healing and
      eruption of succedaneous tooth. Healing was relatively faster and facilitated by
      PRF placement. Furthermore, the importance of anticipatory guidance about the
      treatment of diseased primary teeth and their preservation gets highlighted.

PMID- 29326522
TI  - Fragile X Syndrome: A Rare Case Report with Unusual Oral Features.
AB  - Fragile X syndrome (FXS) is a rare variant of special health-care need
      demonstrating delayed developmental milestones and associated with intellectual
      and emotional disabilities ranging from learning problem to mental retardation.
      The syndrome is usually not diagnosed until 8-9 years of age since the clinical
      manifestations of the syndrome are greatly attenuated in childhood. The physical
      characteristics such as facial features, hyperactivity, attention deficit,
      autistic behavior, and macroorchidism are quite evident in younger age group. The
      most typical orofacial characteristics associated with children suffering from
      FXS are mandibular prominence, ogival, and cleft palate. Till date, very few
      dental literatures have been reported regarding the association of FXS with
      orodental anomalies. Here, we report a rare case of 14-year-old boy suffering
      from FXS with typical orofacial characteristics, multiple supernumerary teeth,
      and dental caries.

PMID- 29326523
TI  - Glandular Odontogenic Cyst: Case Series.
AB  - Glandular odontogenic cyst (GOC) is an uncommon and aggressive jaw cyst with a
      high recurrence rate. It may grow into a large size. Diagnosis of the cyst is
      challenging since it may be confused with some other jaw cysts and malignancies.
      Treatment methods vary from conservative surgery to radical bone resection. In
      this case series, we briefly present five cases of GOC diagnosed and treated at
      our clinic. Thorough histopathological diagnosis and long-term follow-up are
      necessary in patients with GOC.

PMID- 29326524
TI  - Orthodontic Camouflage: A Treatment Option - A Clinical Case Report.
AB  - : Orthodontic camouflage provides an alternative treatment for angle III
      malocclusion since patients with limited economic resources cannot opt for
      orthognathic surgery, it being clear that correction will be achieved at the
      dental level and not at the bone complex. OBJECTIVE: To determine an alternative
      treatment for patients who do not have the possibility of having orthognathic
      surgery. CLINICAL CASE: A 13-year-old female patient, dolico facial biotype with
      slightly concave profile, with Class III Skeletal by mandibular prognathism,
      anterior crossbite, anterior diastema, and large mandibular body, molar class,
      and canine III. Alexander technique brackets were placed; premolar extraction was
      not planned. Once the case was completed, the correction of the anterior
      crossbite was achieved, thanks to the use of the spaces that existed at the
      beginning of the treatment and also that a correct distalization of canines and
      retraction of the lower anterior segment were performed.

PMID- 29326525
TI  - Mucormycosis in a Diabetic Patient: A Case Report with an Insight into Its
      Pathophysiology.
AB  - Mucormycosis is one of the most rapidly progressing and fulminant forms of fungal
      infection which usually begins in the nose and paranasal sinuses following
      inhalation of fungal spores. It is caused by organisms of the subphylum
      Mucormycotina, including genera as Absidia, Mucor, Rhizomucor, and Rhizopus. The
      incidence of mucormycosis is approximately 1.7 cases per 1,000,000 inhabitants
      per year. Mucormycosis affecting the maxilla is rare because of rich blood vessel
      supply of maxillofacial areas although more virulent fungi such as Mucor can
      overcome this difficulty. The common form of this infection is seen in the
      rhinomaxillary region and in patients with immunocompromised state such as
      diabetes. Hence, early diagnosis of this potentially life-threatening disease and
      prompt treatment is of prime importance in reducing the mortality rate.

PMID- 29326526
TI  - Localized Gingival Overgrowths: A Report of Six Cases.
AB  - Localized gingival overgrowths are commonly encountered in our day-to-day
      clinical practice and often present a diagnostic dilemma to the clinicians. These
      lesions vary depending on the location, site, extent, histology, and/or
      etiopathology. Although most of the localized gingival enlargements represent the
      reactive lesion to plaque accumulation, the differential diagnosis ranges from
      peripheral fibroma to pyogenic granuloma to peripheral fibroma with ossification
      and/or calcification, peripheral giant cell granuloma, etc., Even the peripheral
      ameloblastoma may present clinically as a mere localized gingival enlargement.
      Therefore, proper histopathological diagnosis along with biopsy is necessary to
      effectively manage these lesions and to reduce their propensity for recurrence.

PMID- 29326528
TI  - Taking a Glance at Anterior Crossbite in Children: Case Series.
AB  - Anterior crossbite is a malocclusion that takes place for various reasons, leads
      to major problems and may be fixed using various methods. This study aimed to
      provide an update regarding the methods used for anterior crossbite treatment
      presenting treatments of the removable active acrylic appliance with bite plane.
      Clinical examination of aged 9-15, seven healthy children who visited our clinic
      due to crowding and esthetic displeasure in anterior teeth indicated that one or
      more permanent maxillar incisor teeth were positioned behind of permanent
      mandibular incisor teeth. After clinical-radiographical examinations, removable
      active acrylic appliances with bite plane were decided to apply. Patients with
      adapted-activated appliances were called to follow-ups once a week. Treatments
      continued 4-6 weeks in mixed dentition, 7-8 weeks in permanent dentition. In
      choosing the method, advantages-disadvantages, indications-contraindications of
      methods should be discussed. Correct indication and suitable motivation are
      important for the success of anterior crossbite treatment.

PMID- 29326527
TI  - Treatment of a Class II Malocclusion with Deep Overbite in an Adult Patient Using
      Intermaxillary Elastics and Spee Curve Controlling with Reverse and Accentuated
      Archwires.
AB  - This paper aimed to describe the orthodontic treatment of an adult patient with
      the following characteristics: asymmetric Class II malocclusion, left
      subdivision, mandibular midline shifted to the left, mild mandibular anterior
      crowding, excessive overbite, 4-mm overjet, and a brachycephalic facial pattern.
      A 31-year-old male patient, treated with fixed preadjusted appliance with Roth
      prescription, with leveling and alignment NiTi archwire sequence. To correct the
      asymmetric Class II malocclusion, midline shift as well the overjet and overbite,
      intermaxillary elastics and accentuated and reversed stainless steel archwires
      were used, respectively. The posttreatment results showed a Class I molar
      relationship, as well the overjet and overbite correction. These results could be
      achieved due to a correct treatment plan and so to the patient cooperation.

PMID- 29326530
TI  - Pesticide Poisonings in Low- and Middle-Income Countries.
AB  - Aims and scope This editorial is an introduction to the papers making up the
      special issue on 'pesticide poisonings in low- and middle income countries'.

PMID- 29326529
TI  - A Match-Pair Analysis of Open Versus Laparoscopic Liver Surgery.
AB  - Background and Objectives: In addition to general advantages of laparoscopic over
      open surgery, such as better cosmesis and faster recovery, laparoscopic liver
      surgery offers specific advantages. Improved liver function and potentially
      earlier postoperative oncologic treatment are suggested by the literature as
      benefits of laparoscopic over open liver surgery. The purpose of this analysis
      was to analyze the outcomes of laparoscopic liver surgery in our department.
      Methods: All laparoscopic liver resections (LLRs) performed from January 2011
      through July 2016 were identified from the institutional database and matched 1:2
      to open liver resections (OLRs). Data were analyzed regarding perioperative
      outcome, and significance was set at P < .05. Results: Of 1525 liver resections,
      120 patients were included in this analysis. Forty resections were performed
      laparoscopically. Patients in the LLR group more often had benign tumors. No
      patient died after LLR, but 2 required conversion to open surgery (5%) because of
      bleeding. Blood loss (200 vs 500 mL, P < .001) was less and hospital stay (6 vs.
      7 days, P = .001) shorter after LLR. Iwate score, operating time, and the size of
      the resection margins did not differ between the groups. Iwate score correlated
      with operative time (P = .027). Conclusions: Laparoscopic liver surgery was safe,
      and several advantages over open surgery were confirmed in our series.

PMID- 29326531
TI  - Medial Pivot in Total Knee Arthroplasty: Literature Review and Our First
      Experience.
AB  - Background: Traditional total knee implants designs, usually, are not able to
      reproduce the physiological kinematics of the knee, leaving almost 20% of the
      patients, those who underwent a total knee arthroplasty (TKA), not fully
      satisfied. Modern inserts are nowadays designed with a fully congruent medial
      compartment to reproduce the normal medial pivoting biomechanics of the knee. The
      aim of this article was to evaluate preliminary clinical improvement using the
      Medial Congruent (MC) insert as specific level of constraint. Materials and
      methods: A total of 10 consecutive patients have been enrolled in this study and
      treated using an MC tibial polyethylene insert. The Oxford Knee Score (OKS) and
      the Knee Society Score (KSS) have been assessed preoperatively and at 3-month, 6
      month, and 1-year follow-up (FU) and used as validated measurements to evaluate
      early clinical improvements. Postoperative radiological examination was reviewed
      looking for radiolucent lines or loosening of the components. Results: Average
      improvement in OKS was from 19.5 to 41.2, whereas KSS improved with an average
      score from 64.7 preoperatively to 167.5 at the final FU showing good to excellent
      results in 95% of the treated knees. Evaluating the range of motion, the average
      maximum active movement was 124 degrees  and none of the patients needing for a
      revision surgery or manipulation under anesthesia. No complications were observed
      at the final FU as septic or aseptic loosening or vascular or neurologic injury.
      Discussion and conclusions: Medial Congruent insert showed good to excellent
      clinical results at 1-year FU. Range of motion and subjective outcomes were
      satisfying and comparable with results obtained in literature using traditional
      TKA design.

PMID- 29326532
TI  - Rheological Properties of Commercially Available Hyaluronic Acid Products in the
      United States for the Treatment of Osteoarthritis Knee Pain.
AB  - Objective: The inconsistent results within the current literature regarding the
      efficacy of intra-articular-hyaluronic acid (IA-HA) for the treatment of knee
      osteoarthritis (OA) have been suggested to be due to intrinsic differences
      between individual HA products. The purpose of this investigation is to define
      the rheological differences between currently available HA products in the United
      States at the time of this study for the treatment of knee OA, which will help
      elaborate on the appropriateness of classifying HA products as a class opposed to
      as individual agents. Methods: The rheological parameters for Euflexxa,
      Orthovisc, Supartz, Monovisc, Synvisc, Synvisc-One, Gel-One, and Hyalgan were
      obtained with a TA AR 2000 EX Rheometer with a cone-plate geometry (40-mm plate
      diameter and a 2 degrees  cone angle) at room temperature. Results: The bulk
      rheological parameters of the different products suggest molecular structures
      traversing the range of dilute solution (Hyalgan, Supartz), semidilute solution
      (Euflexxa, Orthovisc), entangled solutions (Monovisc, Synvisc, Synvisc-One), and
      even gel-like (Gel-One) behavior. Conclusions: Due to the differences in
      rheological properties between IA-HA products, the universal assessment of these
      products as a class may not be appropriate. Instead, it may be more appropriate
      to assess each product individually. Future research should aim to link these
      differences in rheological properties to the differences in clinical efficacy
      seen across these IA-HA products.

PMID- 29326533
TI  - Manually Steerable Catheter With Improved Agility.
AB  - Purpose: A prototype steerable catheter was designed for endovascular procedures.
      This technical pilot study reports the initial experience using the catheter for
      cannulation of visceral arteries. Technique: The 7F catheter was manually
      steerable with operator control handle for bending and rotation of the tip. The
      maximum bending angle was approximately 90 degrees  and full 360 degrees 
      rotation of the tip was supported. The study involved 1 pig with 4 designated
      target arteries: the left and right renal arteries, the superior mesenteric
      artery, and the celiac trunk. Fluoroscopy with 3-dimensional (3D) overlay showing
      the ostia from preoperative computed tomography angiography was used for image
      guidance. The cannulation was considered successful if the guidewire was placed
      well inside the target artery. In addition to evaluating cannulation success,
      procedure time and associated radiation doses were recorded. The procedure was
      performed twice with 2 different operators. Conclusions: Both operators
      successfully reached all 4 target arteries, demonstrating the feasibility of the
      steerable catheter for endovascular cannulation of visceral arteries. No contrast
      medium was used, and median radiation dose was 4.5 mGy per cannulation. An
      average of approximately 2 minutes was used per cannulation. This study motivates
      further testing in a more comprehensive study to evaluate reproducibility in
      several animals and with inclusion of more operators. Further development by
      integrating the new catheter tool in a navigation system is also an interesting
      next step, combining fine control of catheter tip movements and 3D image guidance
      without ionizing radiation.

PMID- 29326535
TI  - Very Rare Presentation of Cerebrovascular Accident in 20-Year-Old Man With
      Familial Mediterranean Fever-Case Report.
AB  - Familial Mediterranean fever (FMF) is characterized by recurrent episodes of
      fever accompanied by serosal, synovial, or cutaneous inflammation. The central
      nervous system (CNS) is rarely involved in FMF. The CNS involvement includes
      demyelinating lesions, posterior reversible encephalopathy syndrome, pseudotumor
      cerebri, optic neuritis, and cerebral vasculitis. Here, we present a 20-year-old
      man, a known case of FMF with abrupt left-sided hemiparesis. Brain magnetic
      resonance imaging revealed right periventricular infarction. Normal
      echocardiography ruled out cardioembolism, and thrombophilia workup was negative.
      Therefore, FMF-induced cerebrovascular accident was considered. Although rare,
      CNS involvement as a result of FMF disease should also be considered when
      encountering patients with FMF and CNS manifestations.

PMID- 29326536
TI  - First Time Isolation of Mycobacterium hassiacum From a Respiratory Sample.
AB  - We describe the first isolation of Mycobacterium hassiacum, a rapid-growing,
      partial acid-resistant mycobacterium, in a respiratory specimen from a patient
      with exacerbated chronic obstructive pulmonary disease. To provide therapeutic
      recommendation for future cases, antibiotic susceptibility testing of 3 clinical
      isolates was performed by broth microdilution. All strains tested showed
      susceptibility to clarithromycin, imipenem, ciprofloxacin, and doxycycline. The
      role of M hassiacum as a respiratory pathogen remains unclear and needs to be
      evaluated by future reports.

PMID- 29326534
TI  - Is Exercise Training Appropriate for Patients With Advanced Heart Failure
      Receiving Continuous Inotropic Infusion? A Review.
AB  - Exercise-based rehabilitation programs have been reported to have beneficial
      effects for patients with heart failure. However, there is little evidence about
      whether this is the case in patients with more severe heart failure. In
      particular, there is a question in the clinical setting whether patients with
      advanced heart failure and continuous inotropic infusion should be prescribed
      exercise training. In contrast, many studies conclude that prolonged immobility
      associated with heart failure profoundly impairs physical function and promotes
      muscle wasting that could further hasten the course of heart failure. By
      contrast, exercise training has various effects not only in improving exercise
      capacity but also on vascular function, skeletal muscle, and autonomic balance.
      In this review, we summarize the effectiveness and discuss methods of exercise
      training in patients with advanced heart failure receiving continuous inotropic
      agents such as dobutamine.

PMID- 29326537
TI  - Total Ossicular Replacement Prosthesis: A New Fat Interposition Technique.
AB  - Objective: To compare audiometric results between the standard total ossicular
      replacement prosthesis (TORP-S) and a new fat interposition total ossicular
      replacement prosthesis (TORP-F) in pediatric and adult patients and to assess the
      complication and the undesirable outcome. Study design: This is a retrospective
      study. Methods: This study included 104 patients who had undergone titanium
      implants with TORP-F and 54 patients who had undergone the procedure with TORP-S
      between 2008 and 2013 in our tertiary care centers. The new technique consists of
      interposing a fat graft between the 4 legs of the universal titanium prosthesis
      (Medtronic Xomed Inc, Jacksonville, FL, USA) to provide a more stable TORP in the
      ovale window niche. Normally, this prosthesis is designed to fit on the stapes'
      head as a partial ossicular replacement prosthesis. Results: The postoperative
      air-bone gap less than 25 dB for the combined cohort was 69.2% and 41.7% for the
      TORP-F and the TORP-S groups, respectively. The mean follow-up was 17 months
      postoperatively. By stratifying data, the pediatric cohort shows 56.5% in the
      TORP-F group (n = 52) compared with 40% in the TORP-S group (n = 29). However,
      the adult cohort shows 79.3% in the TORP-F group (n = 52) compared with 43.75% in
      the TORP-S group (n = 25). These improvements in hearing were statistically
      significant. There were no statistically significant differences in the speech
      discrimination scores. The only undesirable outcome that was statistically
      different between the 2 groups was the prosthesis displacement: 7% in the TORP-F
      group compared with 19% in the TORP-S group (P = .03). Conclusions: The
      interposition of a fat graft between the legs of the titanium implants (TORP-F)
      provides superior hearing results compared with a standard procedure (TORP-S) in
      pediatric and adult populations because of its better stability in the oval
      window niche.

PMID- 29326538
TI  - Type 2 Diabetes Genetic Risk Scores Are Associated With Increased Type 2 Diabetes
      Risk Among African Americans by Cardiometabolic Status.
AB  - The relationship between genetic risk variants associated with glucose
      homeostasis and type 2 diabetes risk has yet to be fully explored in African
      American populations. We pooled data from 4 prospective studies including 4622
      African Americans to assess whether beta-cell dysfunction (BCD) and/or insulin
      resistance (IR) genetic variants were associated with increased type 2 diabetes
      risk. The BCD genetic risk score (GRS) and combined BCD/IR GRS were significantly
      associated with increased type 2 diabetes risk. In cardiometabolic-stratified
      models, the BCD and IR GRS were associated with increased type 2 diabetes risk
      among 5 cardiometabolic strata: 3 clinically healthy strata and 2 clinically
      unhealthy strata. Genetic risk scores related to BCD and IR were associated with
      increased risk of type 2 diabetes in African Americans. Notably, the GRSs were
      significant predictors of type 2 diabetes among individuals in clinically normal
      ranges of cardiometabolic traits.

PMID- 29326540
TI  - The contribution of differences in adiposity to educational disparities in
      mortality in the United States.
AB  - BACKGROUND: There are large differences in life expectancy by educational
      attainment in the United States. Previous research has found obesity's
      contribution to these differences to be small. Those findings may be sensitive to
      how obesity is estimated. METHODS: This analysis uses discrete-time logistic
      regressions with data from the National Health and Nutrition Examination Survey
      (NHANES), pooled from 1988 to 1994 and 1999 to 2010, to estimate the contribution
      of differences in adiposity, or body fat, to educational differences in
      mortality. I show that results depend upon the measure of adiposity used: body
      mass index (BMI) at the time of survey or lifetime maximum BMI. RESULTS: College
      graduates were less likely than high school graduates to be obese at the time of
      survey (25% vs. 34.6%, respectively) and were also less likely to have ever been
      obese (35.7% vs. 49.4%, respectively). Lifetime maximum BMI performed better than
      BMI at the time of survey in predicting mortality using criteria for model
      selection. Differences in maximum BMI were associated with between 10.3% and 12%
      of mortality differences between college graduates and all others, compared to
      between 3.3% and 4.6% for BMI at the time of survey. Among nonsmokers, between
      18.4% and 27.6% of mortality differences between college graduates and all others
      were associated with differences in maximum BMI. CONTRIBUTION: Adiposity is an
      overlooked contributor to educational differences in mortality. Previous findings
      that obesity does not contribute to educational disparities were based on BMI at
      the time of survey, which is less informative than maximum BMI. The contribution
      of adiposity to educational mortality differences will likely grow as smoking
      prevalence declines. Health surveys should collect information on weight history.

PMID- 29326539
TI  - Microvascular Outcomes of Pediatric-Onset Type 1 Diabetes Mellitus: A Single
      Center Observational Case Reviews in Sana'a, Yemen.
AB  - Microvascular complications of pediatric-onset type 1 diabetes are common in low
      income countries. In this study, we aimed at reviewing microvascular outcomes in
      6 cases with type 1 diabetes over 14 to 31 years of follow-up. Severe
      proliferative diabetic retinopathy (PDR) and/or diabetic macular edema
      (maculopathy) (DME) and overt diabetic nephropathy (macroalbuminuria) were seen
      among 4 of 6 patients, whereas severe diabetic peripheral neuropathy with Charcot
      neuroarthropathy was seen in 1 patient only, who had the longest duration of
      follow-up. The weighted mean (SD) (95% confidence interval) hemoglobin A1c was
      8.9 (1.6) (8.4-9.4)% [74 (17) (68-80) mmol/mol] for PDR/DME and 8.6 (1.7) (8.0
      9.0)% [71 (19) (65-77) mmol/mol] for macroalbuminuria. Thyroid autoimmunity was
      positive in 3 patients with overt hypothyroidism in 2 of them. Worse
      microvascular outcomes among these cases might be attributed to poor glycemic
      control, lack of knowledge, and limited financial resources.

PMID- 29326541
TI  - Assessing the Biological Safety Profession's Evaluation and Control of Risks
      Associated with the Field Collection of Potentially Infectious Specimens.
AB  - Because the origins of the biological safety profession are rooted in the control
      and prevention of laboratory-associated infections, the vocation focuses
      primarily on the safe handling of specimens within the laboratory. But in many
      cases, the specimens and samples handled in the lab are originally collected in
      the field where a broader set of possible exposure considerations may be present,
      each with varying degrees of controllability. The failure to adequately control
      the risks associated with collecting biological specimens in the field may result
      in illness or injury, and could have a direct impact on laboratory safety, if
      infectious specimens were packaged or transported inappropriately, for example.
      This study developed a web-based survey distributed to practicing biological
      safety professionals to determine the prevalence of and extent to which
      biological safety programs consider and evaluate field collection activities. In
      cases where such issues were considered, the data collected characterize the
      types of controls and methods of oversight at the institutional level that are
      employed. Sixty-one percent (61%) of the survey respondents indicated that
      research involving the field collection of biological specimens is conducted at
      their institutions. A majority (79%) of these field collection activities occur
      at academic institutions. Twenty-seven percent (27%) of respondents indicated
      that their safety committees do not consider issues related to biological
      specimens collected in the field, and only 25% with an oversight committee
      charged to review field collection protocols have generated a field research
      specific risk assessment form to facilitate the assembly of pertinent information
      for a project risk assessment review. The results also indicated that most
      biosafety professionals (73% overall; 71% from institutions conducting field
      collection activities) have not been formally trained on the topic, but many (64%
      overall; 87% from institutions conducting field collection activities) indicated
      that training on field research safety issues would be helpful, and even more
      (71% overall; 93% from institutions conducting field collection activities) would
      consider participation in such a training course. Results obtained from this
      study can be used to develop a field research safety toolkit and associated
      training curricula specifically targeted to biological safety professionals.

PMID- 29326543
TI  - Aging Induces Changes in the Somatic Nerve and Postsynaptic Component without Any
      Alterations in Skeletal Muscles Morphology and Capacity to Carry Load of Wistar
      Rats.
AB  - The present study aimed to analyze the morphology of the peripheral nerve,
      postsynaptic compartment, skeletal muscles and weight-bearing capacity of Wistar
      rats at specific ages. Twenty rats were divided into groups: 10 months-old
      (ADULT) and 24 months-old (OLD). After euthanasia, we prepared and analyzed the
      tibial nerve using transmission electron microscopy and the soleus and plantaris
      muscles for cytofluorescence and histochemistry. For the comparison of the
      results between groups we used dependent and independent Student's t-test with
      level of significance set at p <= 0.05. For the tibial nerve, the OLD group
      presented the following alterations compared to the ADULT group: larger area and
      diameter of both myelinated fibers and axons, smaller area occupied by myelinated
      and unmyelinated axons, lower numerical density of myelinated fibers, and fewer
      myelinated fibers with normal morphology. Both aged soleus and plantaris end
      plate showed greater total perimeter, stained perimeter, total area and stained
      area compared to ADULT group (p < 0.05). Yet, aged soleus end-plate presented
      greater dispersion than ADULT samples (p < 0.05). For the morphology of soleus
      and plantaris muscles, density of the interstitial volume was greater in the OLD
      group (p < 0.05). No statistical difference was found between groups in the
      weight-bearing tests. The results of the present study demonstrated that the
      aging process induces changes in the peripheral nerve and postsynaptic
      compartment without any change in skeletal muscles and ability to carry load in
      Wistar rats.

PMID- 29326542
TI  - Current Advances and Limitations in Modeling ALS/FTD in a Dish Using Induced
      Pluripotent Stem Cells.
AB  - Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two age
      dependent multifactorial neurodegenerative disorders, which are typically
      characterized by the selective death of motor neurons and cerebral cortex
      neurons, respectively. These two diseases share many clinical, genetic and
      pathological aspects. During the past decade, cell reprogramming technologies
      enabled researchers to generate human induced pluripotent stem cells (iPSCs) from
      somatic cells. This resulted in the unique opportunity to obtain specific
      neuronal and non-neuronal cell types from patients which could be used for basic
      research. Moreover, these in vitro models can mimic not only the familial forms
      of ALS/FTD, but also sporadic cases without known genetic cause. At present,
      there have been extensive technical advances in the generation of iPSCs, as well
      as in the differentiation procedures to obtain iPSC-derived motor neurons,
      cortical neurons and non-neuronal cells. The major challenge at this moment is to
      determine whether these iPSC-derived cells show relevant phenotypes that
      recapitulate complex diseases. In this review, we will summarize the work related
      to iPSC models of ALS and FTD. In addition, we will discuss potential drawbacks
      and solutions for establishing more trustworthy iPSC models for both ALS and FTD.

PMID- 29326545
TI  - Apolipoprotein Eepsilon4: A Biomarker for Executive Dysfunction among Parkinson's
      Disease Patients with Mild Cognitive Impairment.
AB  - Background: Cognitive impairment is prevalent in Parkinson's disease (PD),
      affecting 15-20% of patients at diagnosis. alpha-synuclein expression and genetic
      polymorphisms of Apolipoprotein E (ApoE) have been associated with the presence
      of cognitive impairment in PD although data have been inconsistent. Objectives:
      To determine the prevalence of cognitive impairment in patients with PD using
      Montreal Cognitive Assessment (MoCA), Comprehensive Trail Making Test (CTMT) and
      Parkinson's disease-cognitive rating scale (PDCRS), and its association with
      plasma alpha-synuclein and ApoE genetic polymorphisms. Methods: This was across
      sectional study involving 46 PD patients. Patients were evaluated using Montreal
      cognitive assessment test (MoCA), and detailed neuropsychological tests. The
      Parkinson's disease cognitive rating scale (PDCRS) was used for cognitive
      function and comprehensive trail making test (CTMT) for executive function. Blood
      was drawn for plasma alpha-synuclein measurements and ApoE genetic analysis. ApoE
      polymorphism was detected using MutaGELAPoE from ImmunDiagnostik. Plasma alpha
      synuclein was detected using the ELISA Technique (USCN Life Science Inc.)
      according to the standard protocol. Results: Based on MoCA, 26 (56.5%) patients
      had mild cognitive impairment (PD-MCI) and 20 (43.5%) had normal cognition (PD
      NC). Based on the PDCRS, 18 (39.1%) had normal cognition (PDCRS-NC), 17 (37%) had
      mild cognitive impairment (PDCRS-MCI), and 11 (23.9%) had dementia (PDCRS-PDD).
      In the PDCRS-MCI group, 5 (25%) patients were from PD-NC group and all PDCRS-PDD
      patients were from PD-MCI group. CTMT scores were significantly different between
      patients with MCI and normal cognition on MoCA (p = 0.003). Twenty one patients
      (72.4%) with executive dysfunction were from the PD-MCI group; 17 (77.3%) with
      severe executive dysfunction and 4 (57.1%) had mild to moderate executive
      dysfunction. There were no differences in the plasma alpha-synuclein
      concentration between the presence or types of cognitive impairment based on
      MoCA, PDCRS, and CTMT. TheApoEe4 allele carrier frequency was significantly
      higher in patients with executive dysfunction (p = 0.014). Conclusion: MCI was
      prevalent in our PD population. PDCRS appeared to be more discriminatory in
      detecting MCI and PDD than MoCA. Plasma alpha-synuclein level was not associated
      with presence nor type of cognitive impairment, but the ApoEe4 allele carrier
      status was significantly associated with executive dysfunction in PD.

PMID- 29326544
TI  - Unraveling the Role of RNA Mediated Toxicity of C9orf72 Repeats in C9-FTD/ALS.
AB  - The most frequent genetic cause of amyotrophic lateral sclerosis (ALS) and
      frontotemporal dementia (FTD) is intronic hexanucleotide (G4C2) repeat expansions
      (HRE) in the C9orf72 gene. The non-exclusive pathogenic mechanisms by which
      C9orf72 repeat expansions contribute to these neurological disorders include loss
      of C9orf72 function and gain-of-function determined by toxic RNA molecules and
      dipeptides repeats protein toxicity. The expanded repeats are transcribed
      bidirectionally and forms RNA foci in the central nervous system, and sequester
      key RNA-binding proteins (RBPs) leading to impairment in RNA processing events.
      Many studies report widespread transcriptome changes in ALS carrying a C9orf72
      repeat expansion. Here we review the contribution of RNA foci interaction with
      RBPs as well as transcriptome changes involved in the pathogenesis of C9orf72-
      associated FTD/ALS. These informations are essential to elucidate the pathology
      and therapeutic intervention of ALS and/or FTD.

PMID- 29326546
TI  - NODDI-DTI: Estimating Neurite Orientation and Dispersion Parameters from a
      Diffusion Tensor in Healthy White Matter.
AB  - The NODDI-DTI signal model is a modification of the NODDI signal model that
      formally allows interpretation of standard single-shell DTI data in terms of
      biophysical parameters in healthy human white matter (WM). The NODDI-DTI signal
      model contains no CSF compartment, restricting application to voxels without CSF
      partial-volume contamination. This modification allowed derivation of analytical
      relations between parameters representing axon density and dispersion, and DTI
      invariants (MD and FA) from the NODDI-DTI signal model. These relations formally
      allow extraction of biophysical parameters from DTI data. NODDI-DTI parameters
      were estimated by applying the proposed analytical relations to DTI parameters
      estimated from the first shell of data, and compared to parameters estimated by
      fitting the NODDI-DTI model to both shells of data (reference dataset) in the WM
      of 14 in vivo diffusion datasets recorded with two different protocols, and in
      simulated data. The first two datasets were also fit to the NODDI-DTI model using
      only the first shell (as for DTI) of data. NODDI-DTI parameters estimated from
      DTI, and NODDI-DTI parameters estimated by fitting the model to the first shell
      of data gave similar errors compared to two-shell NODDI-DTI estimates. The
      simulations showed the NODDI-DTI method to be more noise-robust than the two
      shell fitting procedure. The NODDI-DTI method gave unphysical parameter estimates
      in a small percentage of voxels, reflecting voxelwise DTI estimation error or
      NODDI-DTI model invalidity. In the course of evaluating the NODDI-DTI model, it
      was found that diffusional kurtosis strongly biased DTI-based MD values, and so,
      making assumptions based on healthy WM, a novel heuristic correction requiring
      only DTI data was derived and used to mitigate this bias. Since validations were
      only performed on healthy WM, application to grey matter or pathological WM would
      require further validation. Our results demonstrate NODDI-DTI to be a promising
      model and technique to interpret restricted datasets acquired for DTI analysis in
      healthy white matter with greater biophysical specificity, though its limitations
      must be borne in mind.

PMID- 29326547
TI  - Coordinated Morphogenetic Mechanisms Shape the Vertebrate Eye.
AB  - The molecular bases of vertebrate eye formation have been extensively
      investigated during the past 20 years. This has resulted in the definition of the
      backbone of the gene regulatory networks controlling the different steps of eye
      development and has further highlighted a substantial conservation of these
      networks among vertebrates. Yet, the precise morphogenetic events allowing the
      formation of the optic cup from a small group of cells within the anterior neural
      plate are still poorly understood. It is also unclear if the morphogenetic events
      leading to eyes of very similar shape are indeed comparable among all vertebrates
      or if there are any species-specific peculiarities. Improved imaging techniques
      have enabled to follow how the eye forms in living embryos of a few vertebrate
      models, whereas the development of organoid cultures has provided fascinating
      tools to recapitulate tissue morphogenesis of other less accessible species.
      Here, we will discuss what these advances have taught us about eye morphogenesis,
      underscoring possible similarities and differences among vertebrates. We will
      also discuss the contribution of cell shape changes to this process and how
      morphogenetic and patterning mechanisms integrate to assemble the final
      architecture of the eye.

PMID- 29326548
TI  - A c-Src Inhibitor Peptide Based on Connexin43 Exerts Neuroprotective Effects
      through the Inhibition of Glial Hemichannel Activity.
AB  - The non-receptor tyrosine kinase c-Src is an important mediator in several
      signaling pathways related to neuroinflammation. Our previous study showed that
      cortical injection of kainic acid (KA) promoted a transient increase in c-Src
      activity in reactive astrocytes surrounding the neuronal lesion. As a cell
      penetrating peptide based on connexin43 (Cx43), specifically TAT-Cx43266-283,
      inhibits Src activity, we investigated the effect of TAT-Cx43266-283 on neuronal
      death promoted by cortical KA injections in adult mice. As expected, KA promoted
      neuronal death, estimated by the reduction in NeuN-positive cells and reactive
      gliosis, characterized by the increase in glial fibrillary acidic protein (GFAP)
      expression. Interestingly, TAT-Cx43266-283 injected with KA diminished neuronal
      death and reactive gliosis compared to KA or KA+TAT injections. In order to gain
      insight into the neuroprotective mechanism, we used in vitro models. In primary
      cultured neurons, TAT-Cx43266-283 did not prevent neuronal death promoted by KA,
      but when neurons were grown on top of astrocytes, TAT-Cx43266-283 prevented
      neuronal death promoted by KA. These observations demonstrate the participation
      of astrocytes in the neuroprotective effect of TAT-Cx43266-283. Furthermore, the
      neuroprotective effect was also present in non-contact co-cultures, suggesting
      the contribution of soluble factors released by astrocytes. As glial hemichannel
      activity is associated with the release of several factors, such as ATP and
      glutamate, that cause neuronal death, we explored the participation of these
      channels on the neuroprotective effect of TAT-Cx43266-283. Our results confirmed
      that inhibitors of ATP and NMDA receptors prevented neuronal death in co-cultures
      treated with KA, suggesting the participation of astrocyte hemichannels in
      neurotoxicity. Furthermore, TAT-Cx43266-283 reduced hemichannel activity promoted
      by KA in neuron-astrocyte co-cultures as assessed by ethidium bromide (EtBr)
      uptake assay. In fact, TAT-Cx43266-283 and dasatinib, a potent c-Src inhibitor,
      strongly reduced the activation of astrocyte hemichannels. In conclusion, our
      results suggest that TAT-Cx43266-283 exerts a neuroprotective effect through the
      reduction of hemichannel activity likely mediated by c-Src in astrocytes. These
      data unveil a new role of c-Src in the regulation of Cx43-hemichannel activity
      that could be part of the mechanism by which astroglial c-Src participates in
      neuroinflammation.

PMID- 29326549
TI  - Differential Modulation of GABAA and NMDA Receptors by an alpha7-nicotinic
      Acetylcholine Receptor Agonist in Chronic Glaucoma.
AB  - Presynaptic modulation of gamma-aminobutyric acid (GABA) release by an alpha7
      nicotinic acetylcholine receptor (alpha7-nAChR) agonist promotes retinal ganglion
      cell (RGC) survival and function, as suggested by a previous study on a chronic
      glaucomatous model from our laboratory. However, the role of excitatory and
      inhibitory amino acid receptors and their interaction with alpha7-nAChR in
      physiological and glaucomatous events remains unknown. In this study, we
      investigated GABAA and N-methyl-D-aspartate (NMDA) receptor activity in control
      and glaucomatous retinal slices and the regulation of amino acid receptor
      expression and function by alpha7-nAChR. Whole-cell patch-clamp recordings from
      RGCs revealed that the alpha7-nAChR specific agonist PNU-282987 enhanced the
      amplitude of currents elicited by GABA and reduced the amplitude of currents
      elicited by NMDA. The positive modulation of GABAA receptor and the negative
      modulation of NMDA receptor (NMDAR) by PNU-282987-evoked were prevented by pre
      administration of the alpha7-nAChR antagonist methyllycaconitine (MLA). The
      frequency and the amplitude of glutamate receptor-mediated miniature
      glutamatergic excitatory postsynaptic currents (mEPSCs) were not significantly
      different between the control and glaucomatous RGCs. Additionally, PNU-282987
      treated slices showed no alteration in the frequency or amplitude of mEPSCs
      relative to control RGCs. Moreover, we showed that expression of the alpha1
      subunit of the GABAA receptor was downregulated and the expression of the NMDAR
      NR2B subunit was upregulated by intraocular pressure (IOP) elevation, and the
      changes of high IOP were blocked by PNU-282987. In conclusion, retina GABAA and
      NMDARs are modulated positively and negatively, respectively, by activation of
      alpha7-nAChR in in vivo chronic glaucomatous models.

PMID- 29326550
TI  - Preferential Initiation and Spread of Anoxic Depolarization in Layer 4 of Rat
      Barrel Cortex.
AB  - Anoxic depolarization (AD) is a hallmark of ischemic brain damage. AD is
      associated with a spreading wave of neuronal depolarization and an increase in
      light transmittance. However, initiation and spread of AD across the layers of
      the somatosensory cortex, which is one of the most frequently affected brain
      regions in ischemic stroke, remains largely unknown. Here, we explored the
      initiation and propagation of AD in slices of the rat barrel cortex using
      extracellular local field potential (LFP) recordings and optical intrinsic signal
      (OIS) recordings. We found that ischemia-like conditions induced by oxygen
      glucose deprivation (OGD) evoked AD, which manifested as a large negative LFP
      shift and an increase in light transmittance. AD typically initiated in one or
      more barrels and further spread across the entire slice with a preferential
      propagation through L4. Elevated extracellular potassium concentration
      accelerated the AD onset without affecting proneness of L4 to AD. In live slices,
      barrels were most heavily labeled by the metabolic level marker 2,3,5
      triphenyltetrazolium chloride, suggesting that the highest metabolic demand is in
      L4 when compared to the other layers. Thus, L4 is the layer of the barrel cortex
      most prone to AD, which may be due to the highest metabolic demand and cell
      density in this layer.

PMID- 29326551
TI  - Spinal Cord Cells from Pre-metamorphic Stages Differentiate into Neurons and
      Promote Axon Growth and Regeneration after Transplantation into the Injured
      Spinal Cord of Non-regenerative Xenopus laevis Froglets.
AB  - Mammals are unable to regenerate its spinal cord after a lesion, meanwhile,
      anuran amphibians are capable of spinal cord regeneration only as larvae, and
      during metamorphosis, this capability is lost. Sox2/3+ cells present in the
      spinal cord of regenerative larvae are required for spinal cord regeneration.
      Here we evaluate the effect of the transplantation of spinal cord cells from
      regenerative larvae into the resected spinal cord of non-regenerative stages (NR
      stage). Donor cells were able to survive up to 60 days after transplantation in
      the injury zone. During the first 3-weeks, transplanted cells organize in neural
      tube-like structures formed by Sox2/3+ cells. This was not observed when donor
      cells come from non-regenerative froglets. Mature neurons expressing NeuN and
      Neurofilament-H were detected in the grafted tissue 4 weeks after transplantation
      concomitantly with the appearance of axons derived from the donor cells growing
      into the host spinal cord, suggesting that Sox2/3+ cells behave as neural stem
      progenitor cells. We also found that cells from regenerative animals provide a
      permissive environment that promotes growth and regeneration of axons coming from
      the host. These results suggest that Sox2/3 cells present in the spinal cord of
      regenerative stage (R-stage) larvae are most probably neural stem progenitor
      cells that are able to survive, proliferate, self-organize and differentiate into
      neurons in the environment of the non-regenerative host. In addition, we have
      established an experimental paradigm to study the biology of neural stem
      progenitor cells in spinal cord regeneration.

PMID- 29326552
TI  - Actin Waves Do Not Boost Neurite Outgrowth in the Early Stages of Neuron
      Maturation.
AB  - During neurite development, Actin Waves (AWs) emerge at the neurite base and move
      up to its tip, causing a transient retraction of the Growth Cone (GC). Many
      studies have shown that AWs are linked to outbursts of neurite growth and,
      therefore, contribute to the fast elongation of the nascent axon. Using long term
      live cell-imaging, we show that AWs do not boost neurite outgrowth and that
      neurites without AWs can elongate for several hundred microns. Inhibition of
      Myosin II abolishes the transient GC retraction and strongly modifies the AWs
      morphology. Super-resolution nanoscopy shows that Myosin IIB shapes the growth
      cone-like AWs structure and is differently distributed in AWs and GCs.
      Interestingly, depletion of membrane cholesterol and inhibition of Rho GTPases
      decrease AWs frequency and velocity. Our results indicate that Myosin IIB,
      membrane tension, and small Rho GTPases are important players in the regulation
      of the AW dynamics. Finally, we suggest a role for AWs in maintaining the GCs
      active during environmental exploration.

PMID- 29326553
TI  - The Fast Spiking Subpopulation of Striatal Neurons Coding for Temporal Cognition
      of Movements.
AB  - Background: Timing dysfunctions occur in a number of neurological and psychiatric
      disorders such as Parkinson's disease, obsessive-compulsive disorder, autism and
      attention-deficit-hyperactivity disorder. Several lines of evidence show that
      disrupted timing processing is involved in specific fronto-striatal
      abnormalities. The striatum encodes reinforcement learning and procedural motion,
      and consequently is required to represent temporal information precisely, which
      then guides actions in proper sequence. Previous studies highlighted the temporal
      scaling property of timing-relevant striatal neurons; however, it is still
      unknown how this is accomplished over short temporal latencies, such as the sub
      seconds to seconds range. Methods: We designed a task with a series of timing
      behaviors that required rats to reproduce a fixed duration with robust action.
      Using chronic multichannel electrode arrays, we recorded neural activity from
      dorso-medial striatum in 4 rats performing the task and identified modulation
      response of each neuron to different events. Cell type classification was
      performed according to a multi-criteria clustering analysis. Results: Dorso
      medial striatal neurons (n = 557) were recorded, of which 113 single units were
      considered as timing-relevant neurons, especially the fast-spiking subpopulation
      that had trial-to-trial ramping up or ramping down firing modulation during the
      time estimation period. Furthermore, these timing-relevant striatal neurons had
      to calibrate the spread of their firing pattern by rewarded experience to express
      the timing behavior accurately. Conclusion: Our data suggests that the dynamic
      activities of timing-relevant units encode information about the current duration
      and recent outcomes, which is needed to predict and drive the following action.
      These results reveal the potential mechanism of time calibration in a short
      temporal resolution, which may help to explain the neural basis of motor
      coordination affected by certain physiological or pathological conditions.

PMID- 29326554
TI  - A Variant of the Autophagy-Related 5 Gene Is Associated with Child Cerebral
      Palsy.
AB  - Cerebral palsy (CP) is a major cause of childhood disability in developed and
      developing countries, but the pathogenic mechanisms of CP development remain
      largely unknown. Autophagy is a highly conserved cellular self-digestion of
      damaged organelles and dysfunctional macromolecules. Growing evidence suggests
      that autophagy-related gene 5 (ATG5)-dependent autophagy is involved in neural
      development, neuronal differentiation, and neurological degenerative diseases.
      The aim of this study was to analyze ATG5 protein expression and gene
      polymorphisms in Chinese patients with CP and to evaluate the importance of ATG5
      in the development of CP. Five polymorphisms from different regions of the ATG5
      gene (rs510432, rs3804338, rs573775, rs2299863, and rs6568431) were analyzed in
      715 CP patients and 658 controls using MassARRAY. Of these, 58 patients and 56
      controls were selected for measurement of plasma ATG5 level using ELISA. The
      relevance of disease-associated SNPs was evaluated using the SHEsis program. We
      identified a significant association between rs6568431 and CP (OR = 1.388, 95% CI
      = 1.173~1.643, Pallele = 0.0005, Pgenotype = 0.0015). Subgroup analysis showed a
      highly significant association of rs6568431 with spastic CP (n = 468, OR = 1.511,
      95% CI = 1.251~1.824, Pallele = 8.50e-005, Pgenotype = 1.57e-004) and spastic
      quadriplegia (OR = 1.927, 95% CI = 1.533~2.421, Pallele = 7.35e-008, Pgenotype =
      3.24e-009). Furthermore, mean plasma ATG5 levels were lower in CP patients than
      in controls, and individuals carrying the AA genotype of rs6568431 that was
      positively associated with CP had lower plasma ATG5 levels (P < 0.05). This study
      demonstrated an association of an ATG5 gene variant and low level of ATG5 protein
      with CP, and stronger associations with severe clinical manifestations were
      identified. Our results provide novel evidence for a role of ATG5 in CP and shed
      light on the molecular mechanisms underlying this neurodevelopmental disorder.

PMID- 29326555
TI  - Neurodegeneration: Keeping ATF4 on a Tight Leash.
AB  - Activation of the endoplasmic reticulum (ER) stress and ER stress response, also
      known as the unfolded protein response (UPR), is common to various degenerative
      disorders. Therefore, signaling components of the UPR are currently emerging as
      potential targets for intervention and treatment of human diseases. One UPR
      signaling member, activating transcription factor 4 (ATF4), has been found up
      regulated in many pathological conditions, pointing to therapeutic potential in
      targeting its expression. In cells, ATF4 governs multiple signaling pathways,
      including autophagy, oxidative stress, inflammation, and translation, suggesting
      a multifaceted role of ATF4 in the progression of various pathologies. However,
      ATF4 has been shown to trigger both pro-survival and pro-death pathways, and
      this, perhaps, can explain the contradictory opinions in current literature
      regarding targeting ATF4 for clinical application. In this review, we summarized
      recent published studies from our labs and others that focus on the therapeutic
      potential of the strategy controlling ATF4 expression in different retinal and
      neurodegenerative disorders.

PMID- 29326556
TI  - The Oxidative Stress-Induced Increase in the Membrane Expression of the Water
      Permeable Channel Aquaporin-4 in Astrocytes Is Regulated by Caveolin-1
      Phosphorylation.
AB  - The reperfusion of ischemic brain tissue following a cerebral stroke causes
      oxidative stress, and leads to the generation of reactive oxygen species (ROS).
      Apart from inflicting oxidative damage, the latter may also trigger the
      upregulation of aquaporin 4 (AQP4), a water-permeable channel expressed by
      astroglial cells of the blood-brain barrier (BBB), and contribute to edema
      formation, the severity of which is known to be the primary determinant of
      mortality and morbidity. The mechanism through which this occurs remains unknown.
      In the present study, we have attempted to address this question using primary
      astrocyte cultures treated with hydrogen peroxide (H2O2) as a model system.
      First, we showed that H2O2 induces a significant increase in AQP4 protein levels
      and that this is inhibited by the antioxidant N-acetylcysteine (NAC). Second, we
      demonstrated using cell surface biotinylation that H2O2 increases AQP4 cell
      surface expression independently of it's increased synthesis. In parallel, we
      found that caveolin-1 (Cav1) is phosphorylated in response to H2O2 and that this
      is reversed by the Src kinase inhibitor 4-Amino-5-(4-chlorophenyl)-7-(t
      butyl)pyrazolo[3,4-d]pyrimidine (PP2). PP2 also abrogated the H2O2-induced
      increase in AQP4 surface levels, suggesting that  the phosphorylation of tyrosine
      14 of Cav1 regulates  this  process. We  further  showed  that dominant-negative
      Y14F and phosphomimetic Y14D mutants caused a decrease and increase in AQP4
      membrane expression respectively, and that the knockdown of Cav1 inhibits the
      increase in AQP4 cell-surface, expression following H2O2 treatment. Together,
      these findings suggest that oxidative stress-induced Cav1 phosphorylation
      modulates AQP4 subcellular distribution and therefore may indirectly regulate
      AQP4-mediated water transport.

PMID- 29326557
TI  - TRPC6-mediated ERK1/2 Activation Regulates Neuronal Excitability via Subcellular
      Kv4.3 Localization in the Rat Hippocampus.
AB  - Recently, we have reported that transient receptor potential channel-6 (TRPC6)
      plays an important role in the regulation of neuronal excitability and
      synchronization of spiking activity in the dentate granule cells (DGC). However,
      the underlying mechanisms of TRPC6 in these phenomena have been still unclear. In
      the present study, we investigated the role of TRPC6 in subcellular localization
      of Kv4.3 and its relevance to neuronal excitability in the rat hippocampus. TRPC6
      knockdown increased excitability and inhibitory transmission in the DGC and the
      CA1 neurons in response to a paired-pulse stimulus. However, TRPC6 knockdown
      impaired gamma-aminobutyric acid (GABA)ergic inhibition in the hippocampus during
      and after high-frequency stimulation (HFS). TRPC6 knockdown reduced the Kv4.3
      clusters in membrane fractions and its dendritic localization on DGC and
      GABAergic interneurons. TRPC6 knockdown also decreased extracellular signal
      regulated kinase 1/2 (ERK1/2) phosphorylation and the efficacy of 4-aminopyridine
      (4-AP) in neuronal excitability. An ERK1/2 inhibitor generated multiple
      population spikes in response to a paired-pulse stimulus, concomitant with
      reduced membrane Kv4.3 translocation. A TRPC6 activator (hyperforin) reversed the
      effects of TRPC knockdown, except paired-pulse inhibition. These findings provide
      valuable clues indicating that TRPC6-mediated ERK1/2 activation may regulate
      subcellular Kv4.3 localization in DGC and interneurons, which is cause-effect
      relationship between neuronal excitability and seizure susceptibility.

PMID- 29326558
TI  - Dichotomous Dynamics in E-I Networks with Strongly and Weakly Intra-connected
      Inhibitory Neurons.
AB  - The interconnectivity between excitatory and inhibitory neural networks informs
      mechanisms by which rhythmic bursts of excitatory activity can be produced in the
      brain. One such mechanism, Pyramidal Interneuron Network Gamma (PING), relies
      primarily upon reciprocal connectivity between the excitatory and inhibitory
      networks, while also including intra-connectivity of inhibitory cells. The causal
      relationship between excitatory activity and the subsequent burst of inhibitory
      activity is of paramount importance to the mechanism and has been well studied.
      However, the role of the intra-connectivity of the inhibitory network, while
      important for PING, has not been studied in detail, as most analyses of PING
      simply assume that inhibitory intra-connectivity is strong enough to suppress
      subsequent firing following the initial inhibitory burst. In this paper we
      investigate the role that the strength of inhibitory intra-connectivity plays in
      determining the dynamics of PING-style networks. We show that networks with weak
      inhibitory intra-connectivity exhibit variations in burst dynamics of both the
      excitatory and inhibitory cells that are not obtained with strong inhibitory
      intra-connectivity. Networks with weak inhibitory intra-connectivity exhibit
      excitatory rhythmic bursts with weak excitatory-to-inhibitory synapses for which
      classical PING networks would show no rhythmic activity. Additionally, variations
      in dynamics of these networks as the excitatory-to-inhibitory synaptic weight
      increases illustrates the important role that consistent pattern formation in the
      inhibitory cells serves in maintaining organized and periodic excitatory bursts.
      Finally, motivated by these results and the known diversity of interneurons, we
      show that a PING-style network with two inhibitory subnetworks, one strongly
      intra-connected and one weakly intra-connected, exhibits organized and periodic
      excitatory activity over a larger parameter regime than networks with a
      homogeneous inhibitory population. Taken together, these results serve to better
      articulate the role of inhibitory intra-connectivity in generating PING-like
      rhythms, while also revealing how heterogeneity amongst inhibitory synapses might
      make such rhythms more robust to a variety of network parameters.

PMID- 29326559
TI  - Academic and Behavioral Outcomes in School-Age South African Children Following
      Severe Traumatic Brain Injury.
AB  - Background: Children who have sustained severe traumatic brain injuries (TBIs)
      demonstrate a range of post-injury neurocognitive and behavioral sequelae, which
      may have adverse effects on their academic and behavioral outcomes and interfere
      with school re-entry, educational progress, and quality of life. These post-TBI
      sequelae are exacerbated within the context of a resource-poor country like South
      Africa (SA) where the education system is in a somewhat precarious state
      especially for those from disadvantaged backgrounds. Objectives: To describe
      behavioral and academic outcomes of a group of school-aged SA children following
      severe TBI. Methods: The sample included 27 school-age children who were admitted
      to the Red Cross War Memorial Children's Hospital (RXH), SA, between 2006 and
      2011 for closed severe TBI and who received intracranial monitoring. We collected
      behavioral data using the Child Behavior Checklist (CBCL) and the Behavior Rating
      Inventory of Executive Function (BRIEF) and academic information sourced from the
      BRIEF, CBCL, medical folders, and caregivers. Analyses include descriptive
      statistics and bivariate correlation matrices. Results: The descriptive results
      show that (1) more than half of the participants experienced clinically
      significant behavioral problems across the CBCL scales, (2) the working memory
      BRIEF subscale appeared to be the most problematic subdomain, (3) two thirds of
      the sample were receiving some form of, or were in the process of being placed
      in, special needs education, (4) there was a three-fold increase in the use of
      special education services from pre- to post-injury, and (5) more than half (n =
      16) of the sample repeated at least one grade after returning to school post
      injury. Correlation analyses results suggest that children with increased
      externalizing behavioral problems and executive dysfunction are more likely to
      repeat a grade post-injury; and that children with executive dysfunction post-TBI
      are more likely to require some form of special educational services. Conclusion:
      While there is a vast amount of literature on pediatric TBI (pTBI) academic and
      behavioral outcomes, little literature exists on the pTBI population from the
      developing world and SA specifically. This is important to address given unique
      challenges that face the country and its educational system, and its implications
      for the management and care of children post-TBI.

PMID- 29326561
TI  - Neurotechnology: Current Developments and Ethical Issues.

PMID- 29326560
TI  - Structural Features of an OR37 Glomerulus: A Comparative Study.
AB  - In the olfactory bulb (OB) a sophisticated neuronal network mediates the primary
      processing of sensory information and extensive investigations over the past
      decades have greatly improved our understanding of the morphology and neuronal
      organization of the OB. However, efforts have mostly been focused on the
      different radial layers, typical for the OB and little attention has been paid to
      individual odorant receptor specific glomeruli, the first relay station of
      sensory information. It has been assumed that glomeruli processing odorant
      information out of different contextual fields might require accordingly
      specialized neuronal networks. In this study, we have analyzed and compared the
      structural features as well as cell types in the periglomerular (PG) region of
      three odorant receptor specific glomeruli. The investigations were focused on
      glomeruli of the receptor type OR37A, a member of the unique OR37 subsystem, in
      comparison to glomeruli of OR18-2, a class I odorant receptor and OR256-17, a
      class II receptor. Each of the odorant receptor types is known to be activated by
      distinct odorants and their glomeruli are located in different regions of the
      bulb. We found significant differences in the size of the glomeruli as well as in
      the variability of the glomerulus size in individual mice, whereby the OR37A
      glomeruli featured a remarkably stable size. The number of cells surrounding a
      given glomerulus correlated strongly with its size which allowed comparative
      analyses of the surrounding cell types for individual glomeruli. The proportion
      of PG cells labeled by NeuN as well as putative GABAergic neurons labeled by
      GAD65 was quite similar for the different glomerulus types. However, the number
      of cells expressing distinct calcium-binding proteins, namely parvalbumin (PV),
      calbindin (CB) or calretinin (CR) varied significantly among the three glomerulus
      types. These data suggest that each odorant receptor specific glomerulus type may
      be surrounded by a unique network of PG cells.

PMID- 29326563
TI  - Modulation of Speech Motor Learning with Transcranial Direct Current Stimulation
      of the Inferior Parietal Lobe.
AB  - The inferior parietal lobe (IPL) is a region of the cortex believed to
      participate in speech motor learning. In this study, we investigated whether
      transcranial direct current stimulation (tDCS) of the IPL could influence the
      extent to which healthy adults (1) adapted to a sensory alteration of their own
      auditory feedback, and (2) changed their perceptual representation. Seventy
      subjects completed three tasks: a baseline perceptual task that located the
      phonetic boundary between the vowels /e/ and /a/; a sensorimotor adaptation task
      in which subjects produced the word "head" under conditions of altered or
      unaltered feedback; and a post-adaptation perceptual task identical to the first.
      Subjects were allocated to four groups which differed in current polarity and
      feedback manipulation. Subjects who received anodal tDCS to their IPL (i.e.,
      presumably increasing cortical excitability) lowered their first formant
      frequency (F1) by 10% in opposition to the upward shift in F1 in their auditory
      feedback. Subjects who received the same stimulation with unaltered feedback did
      not change their production. Subjects who received cathodal tDCS to their IPL
      (i.e., presumably decreasing cortical excitability) showed a 5% adaptation to the
      F1 alteration similar to subjects who received sham tDCS. A subset of subjects
      returned a few days later to reiterate the same protocol but without tDCS,
      enabling assessment of any facilitatory effects of the previous tDCS. All
      subjects exhibited a 5% adaptation effect. In addition, across all subjects and
      for the two recording sessions, the phonetic boundary was shifted toward the
      vowel /e/ being repeated, consistently with the selective adaptation effect, but
      a correlation between perception and production suggested that anodal tDCS had
      enhanced this perceptual shift. In conclusion, we successfully demonstrated that
      anodal tDCS could (1) enhance the motor adaptation to a sensory alteration, and
      (2) potentially affect the perceptual representation of those sounds, but we
      failed to demonstrate the reverse effect with the cathodal configuration.
      Overall, tDCS of the left IPL can be used to enhance speech performance but only
      under conditions in which new or adaptive learning is required.

PMID- 29326562
TI  - A Marked Point Process Framework for Extracellular Electrical Potentials.
AB  - Neuromodulations are an important component of extracellular electrical
      potentials (EEP), such as the Electroencephalogram (EEG), Electrocorticogram
      (ECoG) and Local Field Potentials (LFP). This spatially temporal organized multi
      frequency transient (phasic) activity reflects the multiscale spatiotemporal
      synchronization of neuronal populations in response to external stimuli or
      internal physiological processes. We propose a novel generative statistical model
      of a single EEP channel, where the collected signal is regarded as the noisy
      addition of reoccurring, multi-frequency phasic events over time. One of the main
      advantages of the proposed framework is the exceptional temporal resolution in
      the time location of the EEP phasic events, e.g., up to the sampling period
      utilized in the data collection. Therefore, this allows for the first time a
      description of neuromodulation in EEPs as a Marked Point Process (MPP),
      represented by their amplitude, center frequency, duration, and time of
      occurrence. The generative model for the multi-frequency phasic events exploits
      sparseness and involves a shift-invariant implementation of the clustering
      technique known as k-means. The cost function incorporates a robust estimation
      component based on correntropy to mitigate the outliers caused by the inherent
      noise in the EEP. Lastly, the background EEP activity is explicitly modeled as
      the non-sparse component of the collected signal to further improve the
      delineation of the multi-frequency phasic events in time. The framework is
      validated using two publicly available datasets: the DREAMS sleep spindles
      database and one of the Brain-Computer Interface (BCI) competition datasets. The
      results achieve benchmark performance and provide novel quantitative descriptions
      based on power, event rates and timing in order to assess behavioral correlates
      beyond the classical power spectrum-based analysis. This opens the possibility
      for a unifying point process framework of multiscale brain activity where
      simultaneous recordings of EEP and the underlying single neuron spike activity
      can be integrated and regarded as marked and simple point processes,
      respectively.

PMID- 29326565
TI  - Group and Individual Variability in Mouse Pup Isolation Calls Recorded on the
      Same Day Show Stability.
AB  - Mice produce ultrasonic vocalizations (USVs) in a variety of social situations,
      and USVs have been leveraged to study many neurological diseases including verbal
      dyspraxia, depression, autism and stuttering. Pups produce isolation calls, a
      common USV, spontaneously when they are isolated from their mother during the
      first 2 weeks of life. Several genetic manipulations affect (and often reduce)
      pup isolation calls in mice. To facilitate the use of this assay as a means of
      testing whether significant functional differences in genotypes exist instead of
      contextual differences, we test the variability inherent in many commons measures
      of mouse vocalizations. Here we use biological consistency as a way of
      determining which are reproducible in mouse pup vocalizations. We present a
      comprehensive analysis of the normal variability of these vocalizations in groups
      of mice, individual mice and different strains of mice. To control for maturation
      effects, we recorded pup isolation calls in the same group of C57BL/6J 5 days old
      mice twice, with 1 h of rest in between recordings. In almost all cases, the
      group averages between the first and second recordings were the same. We also
      found that there were high correlations in some parameters in individual mice
      across recording while others were not well correlated. These findings could be
      replicated for the majority of features in a separate group of C57BL/6J mice and
      a group of 129/SvEvBrd-C57BL/6J mice. The averages of these mouse USV features
      are highly consistent and represent a robust assay to test the effects of genetic
      and other interventions in the experimental setting.

PMID- 29326564
TI  - Audio Motor Training at the Foot Level Improves Space Representation.
AB  - Spatial representation is developed thanks to the integration of visual signals
      with the other senses. It has been shown that the lack of vision compromises the
      development of some spatial representations. In this study we tested the effect
      of a new rehabilitation device called ABBI (Audio Bracelet for Blind Interaction)
      to improve space representation. ABBI produces an audio feedback linked to body
      movement. Previous studies from our group showed that this device improves the
      spatial representation of space in early blind adults around the upper part of
      the body. Here we evaluate whether the audio motor feedback produced by ABBI can
      also improve audio spatial representation of sighted individuals in the space
      around the legs. Forty five blindfolded sighted subjects participated in the
      study, subdivided into three experimental groups. An audio space localization
      (front-back discrimination) task was performed twice by all groups of subjects
      before and after different kind of training conditions. A group (experimental)
      performed an audio-motor training with the ABBI device placed on their foot.
      Another group (control) performed a free motor activity without audio feedback
      associated with body movement. The other group (control) passively listened to
      the ABBI sound moved at foot level by the experimenter without producing any body
      movement. Results showed that only the experimental group, which performed the
      training with the audio-motor feedback, showed an improvement in accuracy for
      sound discrimination. No improvement was observed for the two control groups.
      These findings suggest that the audio-motor training with ABBI improves audio
      space perception also in the space around the legs in sighted individuals. This
      result provides important inputs for the rehabilitation of the space
      representations in the lower part of the body.

PMID- 29326566
TI  - Investigating Gender Differences under Time Pressure in Financial Risk Taking.
AB  - There is a significant gender imbalance on financial trading floors. This
      motivated us to investigate gender differences in financial risk taking under
      pressure. We used a well-established approach from behavior economics to analyze
      a series of risky monetary choices by male and female participants with and
      without time pressure. We also used second to fourth digit ratio (2D:4D) and face
      width-to-height ratio (fWHR) as correlates of pre-natal exposure to testosterone.
      We constructed a structural model and estimated the participants' risk attitudes
      and probability perceptions via maximum likelihood estimation under both expected
      utility (EU) and rank-dependent utility (RDU) models. In line with existing
      research, we found that male participants are less risk averse and that the
      gender gap in risk attitudes increases under moderate time pressure. We found
      that female participants with lower 2D:4D ratios and higher fWHR are less risk
      averse in RDU estimates. Males with lower 2D:4D ratios were less risk averse in
      EU estimations, but more risk averse using RDU estimates. We also observe that
      men whose ratios indicate a greater prenatal exposure to testosterone exhibit a
      greater optimism and overestimation of small probabilities of success.

PMID- 29326567
TI  - No Robust Association between Static Markers of Testosterone and Facets of Socio
      Economic Decision Making.
AB  - Digit ratio (2D:4D) and facial width-to-height ratio (WHR) are supposedly static
      indicators of testosterone exposition during prenatal and pubertal lifetime,
      respectively. Both measures have been linked to aggressive and assertive behavior
      in laboratory economic games, as well as in real world scenarios. Most of the
      research-often limited to male subjects-considers the associations between these
      behaviors, traits, and hormonal markers separately for 2D:4D and WHR. Reported
      associations are weak and volatile. In the present study we had independent
      raters assess 2D:4D and WHR in a sample of N = 175 participants who played the
      ultimatum game (UG). Respondent behavior in UG captures the tendency to reject
      unfair offers (negative reciprocity). If unfair UG offers are seen as
      provocations, then individuals with stronger testosterone exposition may be more
      prone to reject such offers. Economists argue that negative reciprocity reflects
      altruistic punishment, since the rejecting individual is sacrificing own
      resources. However, recent studies suggest that self-interest, in terms of status
      defense plays a substantial role in decisions to reject unfair offers. We also
      assessed social preferences by social value orientation and assertiveness via
      self-report. By applying structural equation modeling we estimated the latent
      level association of 2D:4D and WHR with negative reciprocity, assertiveness and
      prosociality in both sexes. Results revealed no robust association between any of
      the trait measures and hormonal markers. The measures of 2D:4D and WHR were not
      related with each other. Multigroup models based on sex suggested invariance of
      factor loadings allowing to compare hormone-behavior relationships of females and
      males. Only when collapsing across sex greater WHR was weakly associated with
      assertiveness, suggesting that individuals with wider faces tend to express
      greater status defense. Only the right hand 2D:4D was weakly associated with
      prosocial behavior, indicating that individuals with lower prenatal testosterone
      exposure are more cooperative. Rejection behavior in UG was not related with
      2D:4D nor WHR in any of the models. There were also no curvilinear associations
      between 2D:4D and prosociality as theorized in the literature. Our results
      suggest that previous studies over-estimated the role of static markers of
      testosterone in accounting for aggression and competition behavior in males.

PMID- 29326568
TI  - Tracing the Neural Carryover Effects of Interpersonal Anger on Resting-State fMRI
      in Men and Their Relation to Traumatic Stress Symptoms in a Subsample of
      Soldiers.
AB  - Uncontrolled anger may lead to aggression and is common in various clinical
      conditions, including post traumatic stress disorder. Emotion regulation
      strategies may vary with some more adaptive and efficient than others in reducing
      angry feelings. However, such feelings tend to linger after anger provocation,
      extending the challenge of coping with anger beyond provocation. Task-independent
      resting-state (rs) fMRI may be a particularly useful paradigm to reveal neural
      processes of spontaneous recovery from a preceding negative emotional experience.
      We aimed to trace the carryover effects of anger on endogenous neural dynamics by
      applying a data-driven examination of changes in functional connectivity (FC)
      during rs-fMRI between before and after an interpersonal anger induction (N = 44
      men). Anger was induced based on unfair monetary offers in a previously validated
      decision-making task. We calculated a common measure of global FC (gFC) which
      captures the level of FC between each region and all other regions in the brain,
      and examined which brain regions manifested changes in this measure following
      anger. We next examined the changes in all functional connections of each
      individuated brain region with all other brain regions to reveal which
      connections underlie the differences found in the gFC analysis of the previous
      step. We subsequently examined the relation of the identified neural modulations
      in the aftermath of anger with state- and trait- like measures associated with
      anger, including brain structure, and in a subsample of designated infantry
      soldiers (N = 21), with levels of traumatic stress symptoms (TSS) measured 1 year
      later following combat-training. The analysis pipeline revealed an increase in
      right amygdala gFC in the aftermath of anger and specifically with the right
      inferior frontal gyrus (IFG).We found that the increase in FC between the right
      amygdala and right IFG following anger was positively associated with smaller
      right IFG volume, higher trait-anger level and among soldiers with more TSS.
      Moreover, higher levels of right amygdala gFC at baseline predicted less reported
      anger during the subsequent anger provocation. The results suggest that increased
      amygdala-IFG connectivity following anger is associated with maladaptive
      recovery, and relates to long-term development of stress symptomatology in a
      subsample of soldiers.

PMID- 29326569
TI  - Construct Validity and Reliability of the SARA Gait and Posture Sub-scale in
      Early Onset Ataxia.
AB  - Aim: In children, gait and posture assessment provides a crucial marker for the
      early characterization, surveillance and treatment evaluation of early onset
      ataxia (EOA). For reliable data entry of studies targeting at gait and posture
      improvement, uniform quantitative biomarkers are necessary. Until now, the
      pediatric test construct of gait and posture scores of the Scale for Assessment
      and Rating of Ataxia sub-scale (SARA) is still unclear. In the present study, we
      aimed to validate the construct validity and reliability of the pediatric
      (SARAGAIT/POSTURE) sub-scale. Methods: We included 28 EOA patients [15.5 (6-34)
      years; median (range)]. For inter-observer reliability, we determined the ICC on
      EOA SARAGAIT/POSTURE sub-scores by three independent pediatric neurologists. For
      convergent validity, we associated SARAGAIT/POSTURE sub-scores with: (1) Ataxic
      gait Severity Measurement by Klockgether (ASMK; dynamic balance), (2) Pediatric
      Balance Scale (PBS; static balance), (3) Gross Motor Function Classification
      Scale -extended and revised version (GMFCS-E&R), (4) SARA-kinetic scores
      (SARAKINETIC; kinetic function of the upper and lower limbs), (5) Archimedes
      Spiral (AS; kinetic function of the upper limbs), and (6) total SARA scores
      (SARATOTAL; i.e., summed SARAGAIT/POSTURE, SARAKINETIC, and SARASPEECH sub
      scores). For discriminant validity, we investigated whether EOA co-morbidity
      factors (myopathy and myoclonus) could influence SARAGAIT/POSTURE sub-scores.
      Results: The inter-observer agreement (ICC) on EOA SARAGAIT/POSTURE sub-scores
      was high (0.97). SARAGAIT/POSTURE was strongly correlated with the other ataxia
      and functional scales [ASMK (rs = -0.819; p < 0.001); PBS (rs = -0.943; p <
      0.001); GMFCS-E&R (rs = -0.862; p < 0.001); SARAKINETIC (rs = 0.726; p < 0.001);
      AS (rs = 0.609; p = 0.002); and SARATOTAL (rs = 0.935; p < 0.001)]. Comorbid
      myopathy influenced SARAGAIT/POSTURE scores by concurrent muscle weakness,
      whereas comorbid myoclonus predominantly influenced SARAKINETIC scores.
      Conclusion: In young EOA patients, separate SARAGAIT/POSTURE parameters reveal a
      good inter-observer agreement and convergent validity, implicating the
      reliability of the scale. In perspective of incomplete discriminant validity, it
      is advisable to interpret SARAGAIT/POSTURE scores for comorbid muscle weakness.

PMID- 29326571
TI  - The MindfulBreather: Motion Guided Mindfulness.
AB  - For millennia, humans have focused their attention on the breath to develop
      mindfulness, but finding a scientific way to harness mindful breathing has proven
      elusive. Existing attempts to objectively measure and feedback on mindfulness
      have relied on specialist external hardware including electroencephalograms or
      respirometers that have been impractical for the majority of people learning to
      meditate. Consequently, training in the key skill of breath-awareness has lacked
      practical objective measures and guidance to enhance training. Here, we provide a
      brief technology report on an invention, The MindfulBreather(r) that addresses
      these issues. The technology is available to download embedded in a smartphone
      app that targets, measures and feedbacks on mindfulness of breathing in realtime
      to enhance training. The current article outlines only the technological concept
      with future studies quantifying efficacy, validity and reliability to be reported
      elsewhere. The MindfulBreather works by generating Motion Guided Mindfulness
      through interacting gyroscopic and touchscreen sensors in a three phase process:
      Mindfulness Induction (Phase I) gives standardized instruction to users to place
      their smartphone on their abdomen, breathe mindfully and to tap only at the peak
      of their inhalation. The smartphone's gyroscope detects periodic tilts during
      breathing to generate sinusoidal waveforms. Waveform-tap patterns are analyzed to
      determine whether the user is mindfully tapping only at the correct phase of the
      breathing cycle, indicating psychobiological synchronization. Mindfulness
      Maintenance (Phase II) provides reinforcing pleasant feedback sounds each time a
      breath is mindfully tapped at the right time, and the App records a mindful
      breath. Lastly, data-driven Insights are fed back to the user (Phase III),
      including the number of mindful breaths tapped and breathing rate reductions
      associated with parasympathetic engagement during meditation. The new MGM
      technology is then evaluated and contrasted with traditional mindfulness
      approaches and a novel Psychobiological Synchronization Model is proposed. In
      summary, unlike existing technology, the MindfulBreather requires no external
      hardware and repurposes regular smartphones to deliver app-embedded Motion-Guided
      Mindfulness. Technological applications include reducing mindwandering and down
      regulation of the brain's default mode through enhanced mindful awareness. By
      objectively harnessing breath awareness, The MindfulBreather aims to realize the
      ancient human endeavor of mindfulness for the 21st century.

PMID- 29326570
TI  - Spinal Cord Excitability and Sprint Performance Are Enhanced by Sensory
      Stimulation During Cycling.
AB  - Spinal cord excitability, as assessed by modulation of Hoffmann (H-) reflexes, is
      reduced with fatiguing isometric contractions. Furthermore, spinal cord
      excitability is reduced during non-fatiguing arm and leg cycling. Presynaptic
      inhibition of Ia terminals is believed to contribute to this suppression of
      spinal cord excitability. Electrical stimulation to cutaneous nerves reduces Ia
      presynaptic inhibition, which facilitates spinal cord excitability, and this
      facilitation is present during arm cycling. Although it has been suggested that
      reducing presynaptic inhibition may prolong fatiguing contractions, it is unknown
      whether sensory stimulation can alter the effects of fatiguing exercise on
      performance or spinal cord excitability. Thus, the aim of this experiment was to
      determine if sensory stimulation can interfere with fatigue-related suppression
      of spinal cord excitability, and alter fatigue rates during cycling sprints.
      Thirteen participants randomly performed three experimental sessions that
      included: unloaded cycling with sensory stimulation (CONTROL + STIM), sprints
      with sensory stimulation (SPRINT + STIM) and sprints without stimulation
      (SPRINT). Seven participants also performed a fourth session (CONTROL), which
      consisted of unloaded cycling. During SPRINT and SPRINT + STIM, participants
      performed seven, 10 s cycling sprints interleaved with 3 min rest. For CONTROL
      and CONTROL + STIM, participants performed unloaded cycling for ~30 min. During
      SPRINT + STIM and CONTROL + STIM, participants received patterned sensory
      stimulation to nerves of the right foot. H-reflexes and M-waves of the right
      soleus were evoked by stimulation of the tibial nerve at multiple time points
      throughout exercise. Sensory stimulation facilitated soleus H-reflexes during
      unloaded cycling, whereas sprints suppressed soleus H-reflexes. While receiving
      sensory stimulation, there was less suppression of soleus H-reflexes and slowed
      reduction in average power output, compared to sprints without stimulation. These
      results demonstrate that sensory stimulation can substantially mitigate the
      fatiguing effects of sprints.

PMID- 29326572
TI  - Differential Effects of Carbohydrates on Behavioral and Neuroelectric Indices of
      Selective Attention in Preadolescent Children.
AB  - The importance of breakfast consumption for ideal cognitive performance has
      received much attention in recent years, although research on the topic has
      yielded mixed results. The present study utilized event-related brain potentials
      (ERPs) elicited during a modified flanker task to investigate the neuroelectric
      implications of receiving different mixed macronutrient beverages after an
      overnight fast. A repeated measures design was employed whereby preadolescent
      participants (9-10 years of age) completed cognitive testing while ERPs were
      collected during two non-consecutive testing sessions, one in which they received
      one of three treatment beverages consisting of mixed-macronutrient formulations
      (either Carbohydrate Blend, Sucrose, Maltodextrin) and the other in which they
      received a placebo drink containing Sucralose. Performance indices, ERPs, and
      blood glucose were recorded at three time points before the testing session and
      after the ingestion of each drink. While the behavioral performance indices and
      N2 results showed some evidence of glucose facilitation, the effects were small
      and selective. Participants who received the Maltodextrin treatment showed faster
      reaction times and more stable N2 amplitudes after ingesting the treatment
      beverage. The most robust effects were seen in the P3 amplitude measurement.
      Across the three drink groups, participants showed a marked amplitude increase
      over time after the placebo drink was ingested, although P3 amplitudes remained
      stable when a carbohydrate treatment drink was ingested. These effects were
      eliminated when changes in blood glucose were accounted for, suggesting that the
      neurolectric effects were directly related to glycemic change. These findings
      suggest that ingestion of carbohydrates after an overnight fast results in
      changes to the P3 amplitude of the ERP waveform elicited during an attentional
      inhibition task.

PMID- 29326573
TI  - Two Processes in Early Bimanual Motor Skill Learning.
AB  - Most daily activities are bimanual and their efficient performance requires
      learning and retention of bimanual coordination. Despite in-depth knowledge of
      the various stages of motor skill learning in general, how new bimanual
      coordination control policies are established is still unclear. We designed a new
      cooperative bimanual task in which subjects had to move a cursor across a complex
      path (a circuit) as fast and as accurately as possible through coordinated
      bimanual movements. By looking at the transfer of the skill between different
      circuits and by looking at training with varying circuits, we identified two
      processes in early bimanual motor learning. Loss of performance due to the switch
      in circuit after 15 min of training amounted to 20%, which suggests that a
      significant portion of improvements in bimanual performance is specific to the
      used circuit (circuit-specific skill). In contrast, the loss of performance due
      to the switch in circuit was 5% after 4 min of training. This suggests that
      learning the new bimanual coordination control policy dominates early in the
      training and is independent of the used circuit. Finally, switching between two
      circuits throughout training did not affect the early stage of learning (i.e.,
      the first few minutes), but did affect the later stage. Together, these results
      suggest that early bimanual motor skill learning includes two different
      processes. Learning the new bimanual coordination control policy predominates in
      the first minutes whereas circuit-specific skill improvements unfold later in
      parallel with further improvements in the bimanual coordination control policy.

PMID- 29326574
TI  - Response: Commentary: Skilled Bimanual Training Drives Motor Cortex Plasticity in
      Children with Unilateral Cerebral Palsy.

PMID- 29326575
TI  - Posture Used in fMRI-PET Elicits Reduced Cortical Activity and Altered
      Hemispheric Asymmetry with Respect to Sitting Position: An EEG Resting State
      Study.
AB  - Horizontal body position is a posture typically adopted for sleeping or during
      brain imaging recording in both neuroscience experiments and diagnostic
      situations. Recent literature showed how this position and similar ones with head
      down are associated to reduced plasticity, impaired pain and emotional responses.
      The present study aimed at further understanding the decrease of cortical
      activity associated with horizontal body position by measuring high-frequency EEG
      bands - typically associated with high-level cognitive activation - in a resting
      state experimental condition. To this end, two groups of 16 female students were
      randomly assigned to either sitting control (SC) or 2-h horizontal Bed Rest
      condition (hBR) while EEG was recorded from 38 scalp recording sites. The hBR
      group underwent several body transitions, from sitting to supine, and from supine
      to sitting. Results revealed a clear effect of horizontal posture: the hBR group
      showed, compared to its baseline and to SC, reduced High-Beta and Gamma EEG band
      amplitudes throughout the 2-h of hBR condition. In addition, before and after the
      supine condition, hBR group as well as SC exhibited a greater left vs. right
      frontal activation in both EEG bands while, on the contrary, the supine position
      induced a bilateral and reduced activation in hBR participants. The cortical
      sources significantly more active in SC compared with hBR participants included
      the left Inferior Frontal Gyrus and left Insula. Results are discussed in
      relation to the differences among neuroimaging methods (e.g., fMRI, EEG, NIRS),
      which can be partially explained by posture-induced neural network changes.

PMID- 29326576
TI  - Dynamic Changes in Upper-Limb Corticospinal Excitability during a 'Pro-/Anti
      saccade' Double-Choice Task.
AB  - Under natural behavioral conditions, visually guided eye movements are linked to
      direction-specific modulations of cortico-spinal system (CSS) excitability in
      upper-limb muscles, even in absence of a manual response. These excitability
      changes have been shown to be compatible with a covert motor program encoding a
      manual movement toward the same target of the eyes. The aim of this study is to
      investigate whether this implicit oculo-manual coupling is enforced following
      every saccade execution or it depends on the behavioral context. Twenty-two
      healthy young adults participated in the study. Single-pulse transcranial
      magnetic stimulation was applied to the motor cortex at nine different time
      epochs during a double-choice eye task, in which the decision to execute a
      prosaccade or an antisaccade was made on the color of a peripheral visual cue. By
      analyzing the amplitude of the motor evoked potentials (MEP) in three distal
      muscles of the resting upper-limb, a facilitation peak of CSS excitability was
      found in two of them at 120 ms before the eyes begin to move. Furthermore, a long
      lasting, generalized reduced corticomotor excitability develops following the eye
      response. Finally, a quite large modulation of MEP amplitude, depending on the
      direction of the saccade, is observed only in the first dorsal interosseous
      muscle, in a narrow time window at about 150 ms before the eye movement,
      irrespective of the type of the ocular response (pro-/anti-saccade). This change
      in CSS excitability is not tied up to the timing of the occurrence of the visual
      cue but, instead, appears to be tightly time-related to the saccade onset.
      Observed excitability changes differ in many respects from those previously
      reported with different behavioral paradigms. A main finding of our study is that
      the implicit coupling between eye and hand motor systems is contingent upon the
      particular motor set determined by the cognitive aspects of the performed
      oculomotor task. In particular, the direction-specific modulation in CSS
      excitability described in this study appears to be related to perceptual and
      decision-making processes rather than representing an implicit upper-limb motor
      program, coupled to the saccade execution.

PMID- 29326579
TI  - Interactive Light Stimulus Generation with High Performance Real-Time Image
      Processing and Simple Scripting.
AB  - Light stimulation with precise and complex spatial and temporal modulation is
      demanded by a series of research fields like visual neuroscience, optogenetics,
      ophthalmology, and visual psychophysics. We developed a user-friendly and
      flexible stimulus generating framework (GEARS GPU-based Eye And Retina
      Stimulation Software), which offers access to GPU computing power, and allows
      interactive modification of stimulus parameters during experiments. Furthermore,
      it has built-in support for driving external equipment, as well as for
      synchronization tasks, via USB ports. The use of GEARS does not require elaborate
      programming skills. The necessary scripting is visually aided by an intuitive
      interface, while the details of the underlying software and hardware components
      remain hidden. Internally, the software is a C++/Python hybrid using OpenGL
      graphics. Computations are performed on the GPU, and are defined in the GLSL
      shading language. However, all GPU settings, including the GPU shader programs,
      are automatically generated by GEARS. This is configured through a method
      encountered in game programming, which allows high flexibility: stimuli are
      straightforwardly composed using a broad library of basic components. Stimulus
      rendering is implemented solely in C++, therefore intermediary libraries for
      interfacing could be omitted. This enables the program to perform computationally
      demanding tasks like en-masse random number generation or real-time image
      processing by local and global operations.

PMID- 29326577
TI  - Does Transcranial Direct Current Stimulation Combined with Peripheral Electrical
      Stimulation Have an Additive Effect in the Control of Hip Joint Osteonecrosis
      Pain Associated with Sickle Cell Disease? A Protocol for a One-Session Double
      Blind, Block-Randomized Clinical Trial.
AB  - Chronic pain in Sickle Cell Disease (SCD) is probably related to maladaptive
      plasticity of brain areas involved in nociceptive processing. Transcranial Direct
      Current Stimulation (tDCS) and Peripheral Electrical Stimulation (PES) can
      modulate cortical excitability and help to control chronic pain. Studies have
      shown that combined use of tDCS and PES has additive effects. However, to date,
      no study investigated additive effects of these neuromodulatory techniques on
      chronic pain in patients with SCD. This protocol describes a study aiming to
      assess whether combined use of tDCS and PES more effectively alleviate pain in
      patients with SCD compared to single use of each technique. The study consists of
      a one-session double blind, block-randomized clinical trial (NCT02813629) in
      which 128 participants with SCD and femoral osteonecrosis will be enrolled.
      Stepwise procedures will occur on two independent days. On day 1, participants
      will be screened for eligibility criteria. On day 2, data collection will occur
      in four stages: sample characterization, baseline assessment, intervention, and
      post-intervention assessment. These procedures will last ~5 h. Participants will
      be divided into two groups according to homozygous for S allele (HbSS) (n = 64)
      and heterozygous for S and C alleles (HbSC) (n = 64) genotypes. Participants in
      each group will be randomly assigned, equally, to one of the following
      interventions: (1) active tDCS + active PES; (2) active tDCS + sham PES; (3) sham
      tDCS + active PES; and (4) sham tDCS + sham PES. Active tDCS intervention will
      consist of 20 min 2 mA anodic stimulation over the primary motor cortex
      contralateral to the most painful hip. Active PES intervention will consist of 30
      min sensory electrical stimulation at 100 Hz over the most painful hip. The main
      study outcome will be pain intensity, measured by a Visual Analogue Scale. In
      addition, electroencephalographic power density, cortical maps of the gluteus
      maximus muscle elicited by Transcranial Magnetic Stimulation (TMS), serum levels
      of Brain-derived Neurotrophic Factor (BDNF), and Tumor Necrosis Factor (TNF) will
      be assessed as secondary outcomes. Data will be analyzed using ANOVA of repeated
      measures, controlling for confounding variables.

PMID- 29326580
TI  - The Passive Series Stiffness That Optimizes Torque Tracking for a Lower-Limb
      Exoskeleton in Human Walking.
AB  - This study uses theory and experiments to investigate the relationship between
      the passive stiffness of series elastic actuators and torque tracking performance
      in lower-limb exoskeletons during human walking. Through theoretical analysis
      with our simplified system model, we found that the optimal passive stiffness
      matches the slope of the desired torque-angle relationship. We also conjectured
      that a bandwidth limit resulted in a maximum rate of change in torque error that
      can be commanded through control input, which is fixed across desired and passive
      stiffness conditions. This led to hypotheses about the interactions among optimal
      control gains, passive stiffness and desired quasi-stiffness. Walking experiments
      were conducted with multiple angle-based desired torque curves. The observed
      lowest torque tracking errors identified for each combination of desired and
      passive stiffnesses were shown to be linearly proportional to the magnitude of
      the difference between the two stiffnesses. The proportional gains corresponding
      to the lowest observed errors were seen inversely proportional to passive
      stiffness values and to desired stiffness. These findings supported our
      hypotheses, and provide guidance to application-specific hardware customization
      as well as controller design for torque-controlled robotic legged locomotion.

PMID- 29326578
TI  - Audiovisual Rehabilitation in Hemianopia: A Model-Based Theoretical
      Investigation.
AB  - Hemianopic patients exhibit visual detection improvement in the blind field when
      audiovisual stimuli are given in spatiotemporally coincidence. Beyond this
      "online" multisensory improvement, there is evidence of long-lasting, "offline"
      effects induced by audiovisual training: patients show improved visual detection
      and orientation after they were trained to detect and saccade toward visual
      targets given in spatiotemporal proximity with auditory stimuli. These effects
      are ascribed to the Superior Colliculus (SC), which is spared in these patients
      and plays a pivotal role in audiovisual integration and oculomotor behavior.
      Recently, we developed a neural network model of audiovisual cortico-collicular
      loops, including interconnected areas representing the retina, striate and
      extrastriate visual cortices, auditory cortex, and SC. The network simulated
      unilateral V1 lesion with possible spared tissue and reproduced "online" effects.
      Here, we extend the previous network to shed light on circuits, plastic
      mechanisms, and synaptic reorganization that can mediate the training effects and
      functionally implement visual rehabilitation. The network is enriched by the
      oculomotor SC-brainstem route, and Hebbian mechanisms of synaptic plasticity, and
      is used to test different training paradigms (audiovisual/visual stimulation in
      eye-movements/fixed-eyes condition) on simulated patients. Results predict
      different training effects and associate them to synaptic changes in specific
      circuits. Thanks to the SC multisensory enhancement, the audiovisual training is
      able to effectively strengthen the retina-SC route, which in turn can foster
      reinforcement of the SC-brainstem route (this occurs only in eye-movements
      condition) and reinforcement of the SC-extrastriate route (this occurs in
      presence of survived V1 tissue, regardless of eye condition). The retina-SC
      brainstem circuit may mediate compensatory effects: the model assumes that
      reinforcement of this circuit can translate visual stimuli into short-latency
      saccades, possibly moving the stimuli into visual detection regions. The retina
      SC-extrastriate circuit is related to restitutive effects: visual stimuli can
      directly elicit visual detection with no need for eye movements. Model
      predictions and assumptions are critically discussed in view of existing
      behavioral and neurophysiological data, forecasting that other oculomotor
      compensatory mechanisms, beyond short-latency saccades, are likely involved, and
      stimulating future experimental and theoretical investigations.

PMID- 29326581
TI  - Effects of Dual-Task Management and Resistance Training on Gait Performance in
      Older Individuals: A Randomized Controlled Trial.
AB  - Background: Dual-task (DT) training is a well-accepted modality for fall
      prevention in older adults. DT training should include task-managing strategies
      such as task switching or task prioritization to improve gait performance under
      DT conditions. Methods: We conducted a randomized controlled trial to evaluate a
      balance and task managing training (BDT group) in gait performance compared to a
      single task (ST) strength and resistance training and a control group, which
      received no training. A total of 78 older individuals (72.0 +/- 4.9 years)
      participated in this study. The DT group performed task managing training
      incorporating balance and coordination tasks while the ST group performed
      resistance training only. Training consisted of 12 weekly sessions, 60 min each,
      for 12 weeks. We assessed the effects of ST and BDT training on walking
      performance under ST and DT conditions in independent living elderly adults. ST
      and DT walking (visual verbal Stroop task) were measured utilizing a treadmill at
      self-selected walking speed (mean for all groups: 4.4 +/- 1 km h-1). Specific
      gait variables, cognitive performance, and fear of falling were compared between
      all groups. >Results: Training improved gait performance for step length (p <
      0.001) and gait-line (ST: p < 0.01; DT p < 0.05) in both training groups. The BDT
      training group showed greater improvements in step length (p < 0.001) and gait
      line (p < 0.01) during DT walking but did not have changes in cognitive
      performance. Both interventions reduced fear of falling (p < 0.05). Conclusion:
      Implementation of task management strategies into balance and strength training
      in our population revealed a promising modality to prevent falls in older
      individuals. Trial registration: German register of clinical trials DRKS00012382.

PMID- 29326582
TI  - Anodal Transcranial Direct Current Stimulation Promotes Frontal Compensatory
      Mechanisms in Healthy Elderly Subjects.
AB  - Recent studies have demonstrated that transcranial direct current stimulation
      (tDCS) is potentially useful to improve working memory. In the present study,
      young and elderly subjects performed a working memory task (n-back task) during
      an electroencephalogram recording before and after receiving anodal, cathodal,
      and sham tDCS over the left dorsolateral prefrontal cortex (DLPFC). We
      investigated modulations of behavioral performance and electrophysiological
      correlates of working memory processes (frontal and parietal P300 event-related
      potentials). A strong tendency to modulated working memory performance was
      observed after the application of tDCS. In detail, young, but not elderly,
      subjects benefited from additional practice in the absence of real tDCS, as
      indicated by their more accurate responses after sham tDCS. The cathodal tDCS had
      no effect in any group of participants. Importantly, anodal tDCS improved
      accuracy in elderly. Moreover, increased accuracy after anodal tDCS was
      correlated with a larger frontal P300 amplitude. These findings suggest that, in
      elderly subjects, improved working memory after anodal tDCS applied over the left
      DLPFC may be related to the promotion of frontal compensatory mechanisms, which
      are related to attentional processes.

PMID- 29326583
TI  - Pharmaceutical Regulation in Central and Eastern European Countries: A Current
      Review.
AB  - Objectives: The aim of this study was to review reimbursement environment as well
      as pricing and reimbursement requirements for drugs in selected Central and
      Eastern Europe (CEE) countries. Methods: A questionnaire-based survey was
      performed in the period from November 2016 to March 2017 among experts involved
      in reimbursement matters from CEE countries: Bulgaria, Croatia, Czech Republic,
      Estonia, Hungary, Latvia, Lithuania, Poland, Slovakia, and Romania. A review of
      requirements for reimbursement and implications of Health Technology Assessment
      (HTA) was performed to compare the issues in above-mentioned countries. For each
      specified country, data for reimbursement costs, total pharmaceutical budget, and
      total public health care budget in the years 2014 and 2015 were also collected.
      Questionnaires were distributed via emails and feedback data were obtained in the
      same way. Additional questions, if any, were also submitted to respondents by
      email. Pricing and reimbursement data were valid for March 2017. Results: The
      survey revealed that the relation of drug reimbursement costs to total public
      healthcare spending ranged from 0.12 to 0.21 in the year 2014 and 2015 (median
      value). It also revealed that pricing criteria for drugs, employed in the CEE
      countries, were quite similar. External reference pricing as well as internal
      reference pricing were common in mentioned countries. Positive reimbursement
      lists were valid in all countries of the CEE region, negative ones were rarely
      used; reimbursement decisions were regularly revised and updated in the majority
      of countries. Copayment was common and available levels of reimbursement differed
      within and between the countries and ranged from 20 to 100%. Risk-sharing schemes
      were often in use, especially in the case of innovative, expensive drugs. Generic
      substitution was also possible in all analyzed CEE countries, while some made it
      mandatory. HTA was carried out in almost all of the considered CEE countries and
      HTA dossier was obligatory for submitting a pricing and reimbursement
      application. Conclusions: Pricing and reimbursement requirements are quite
      similar in the CEE region although some differences were identified. HTA
      evaluations are commonly used in considered countries.

PMID- 29326584
TI  - A Combined LC-MS Metabolomics- and 16S rRNA Sequencing Platform to Assess
      Interactions between Herbal Medicinal Products and Human Gut Bacteria in Vitro: a
      Pilot Study on Willow Bark Extract.
AB  - Herbal preparations are complex mixtures of natural products, many of which are
      able to reach the distal gut due to low oral bioavailability. There, they can
      influence the microbial communities, and can be metabolized into potentially
      absorbable bioactive compounds by the intestinal bacteria. This aspect has often
      been disregarded when searching for the active principles of medicinal plants and
      herbal medicinal products. The aim of this study was to establish an
      interdisciplinary platform to unravel interactions of herbal medicine and
      intestinal microbiota, using a combined LC-MS metabolomics and 16S rRNA
      microbiome sequencing approach. Willow bark extract (WBE), a herbal medicinal
      product with a long history of traditional use and a well-established anti
      inflammatory activity, was incubated with human fecal suspension under anoxic
      conditions. Samples were taken after 0.5, 4, and 24 h of incubation. Microbiome
      analyses revealed that incubation with WBE had a marked effect on microbial
      community composition and functions. For example, the proportion of Bacteroides
      sp. was clearly enhanced when the fecal sample used in this study was incubated
      with WBE. LC-MS analysis showed that WBE constituents were readily metabolized by
      fecal bacteria. Numerous microbial metabolites could be annotated, allowing the
      construction of putative microbial degradation pathways for the main groups of
      WBE constituents. We suggest that studies of this type help to increase the
      knowledge on bioactive principles of medicinal plants, since gut microbial
      metabolites might have been underestimated as a source of bioactive compounds in
      the past.

PMID- 29326585
TI  - In Vitro Pro-apoptotic and Anti-migratory Effects of Ficus deltoidea L. Plant
      Extracts on the Human Prostate Cancer Cell Lines PC3.
AB  - This study aims to evaluate the in vitro cytotoxic and anti-migratory effects of
      Ficus deltoidea L. on prostate cancer cells, identify the active compound/s and
      characterize their mechanism of actions. Two farmed varieties were studied, var.
      angustifolia (FD1) and var. deltoidea (FD2). Their crude methanolic extracts were
      partitioned into n-hexane (FD1h, FD2h) chloroform (FD1c, FD2c) and aqueous
      extracts (FD1a, FD2a). Antiproliferative fractions (IC50 < 30 MUg/mL, SRB
      staining of PC3 cells) were further fractionated. Active compound/s were
      dereplicated using spectroscopic methods. In vitro mechanistic studies on PC3
      and/or LNCaP cells included: annexin V-FITC staining, MMP depolarization
      measurements, activity of caspases 3 and 7, nuclear DNA fragmentation and cell
      cycle analysis, modulation of Bax, Bcl-2, Smac/Diablo, and Alox-5 mRNA gene
      expression by RT-PCR. Effects of cytotoxic fractions on 2D migration and 3D
      invasion were tested by exclusion assays and modified Boyden chamber,
      respectively. Their mechanisms of action on these tests were further studied by
      measuring the expression VEGF-A, CXCR4, and CXCL12 in PC3 cells by RT-PCR. FD1c
      and FD2c extracts induced cell death (P < 0.05) via apoptosis as evidenced by
      nuclear DNA fragmentation. This was accompanied by an increase in MMP
      depolarization (P < 0.05), activation of caspases 3 and 7 (P < 0.05) in both PC3
      and LNCaP cell lines. All active plant extracts up-regulated Bax and Smac/DIABLO,
      down-regulated Bcl-2 (P < 0.05). Both FD1c and FD2c were not cytotoxic against
      normal human fibroblast cells (HDFa) at the tested concentrations. Both plant
      extracts inhibited both migration and invasion of PC3 cells (P < 0.05). These
      effects were accompanied by down-regulation of both VEGF-A and CXCL-12 gene
      expressions (P < 0.001). LC-MS dereplication using taxonomy filters and molecular
      networking databases identified isovitexin in FD1c; and oleanolic acid,
      moretenol, betulin, lupenone, and lupeol in FD2c. In conclusion, FD1c and FD2c
      were able to overcome three main hallmarks of cancer in PC3 cells: (1) apoptosis
      by activating of the intrinsic pathway, (2) inhibition of both migration and
      invasion by modulating the CXCL12-CXCR4 axis, and (3) inhibiting angiogenesis by
      modulating VEGF-A expression. Moreover, isovitexin is here reported for the first
      time as an antiproliferative principle (IC50 = 43 MUg/mL, SRB staining of PC3
      cells).

PMID- 29326586
TI  - Bio-Catalytic Structural Transformation of Anti-cancer Steroid, Drostanolone
      Enanthate with Cephalosporium aphidicola and Fusarium lini, and Cytotoxic
      Potential Evaluation of Its Metabolites against Certain Cancer Cell Lines.
AB  - In search of selective and effective anti-cancer agents, eight metabolites of
      anti-cancer steroid, drostanolone enanthate (1), were synthesized via microbial
      biotransformation. Enzymes such as reductase, oxidase, dehydrogenase, and
      hydrolase from Cephalosporium aphidicola, and Fusarium lini were likely involved
      in the biotransformation of 1 into new metabolites at pH 7.0 and 26 degrees C,
      yielding five new metabolites, 2alpha-methyl-3alpha,14alpha,17beta-trihydroxy
      5alpha-androstane (2), 2alpha-methyl-7alpha-hydroxy-5alpha-androstan-3,17-dione
      (3), 2-methylandrosta-11alpha-hydroxy-1, 4-diene-3,17-dione (6), 2-methylandrosta
      14alpha-hydroxy-1,4-diene-3,17-dione (7), and 2-methyl-5alpha-androsta-7alpha
      hydroxy-1-ene-3,17-dione (8), along with three known metabolites, 2alpha-methyl
      3alpha,17beta-dihydroxy-5alpha-androstane (4), 2-methylandrosta-1, 4-diene-3,17
      dione (5), and 2alpha-methyl-5alpha-androsta-17beta-hydroxy-3-one (9), on the
      basis of NMR, and HREI-MS data, and single-crystal X-ray diffraction techniques.
      Interestingly, C. aphidicola and F. lini were able to catalyze hydroxylation only
      at alpha positions of 1. Compounds 1-9 showed a varying degree of cytotoxicity
      against HeLa (human cervical carcinoma), PC3 (human prostate carcinoma), H460
      (human lung cancer), and HCT116 (human colon cancer) cancer cell lines.
      Interestingly, metabolites 4 (IC50 = 49.5 +/- 2.2 MUM), 5 (IC50 = 39.8 +/- 1.5
      MUM), 6 (IC50 = 40.7 +/- 0.9 MUM), 7 (IC50 = 43.9 +/- 2.4 MUM), 8 (IC50 = 19.6 +/
      1.4 MUM), and 9 (IC50 = 25.1 +/- 1.6 MUM) were found to be more active against
      HeLa cancer cell line than the substrate 1 (IC50 = 54.7 +/- 1.6 MUM). Similarly,
      metabolites 2 (IC50 = 84.6 +/- 6.4 MUM), 3 (IC50 = 68.1 +/- 1.2 MUM), 4 (IC50 =
      60.4 +/- 0.9 MUM), 5 (IC50 = 84.0 +/- 3.1 MUM), 6 (IC50 = 58.4 +/- 1.6 MUM), 7
      (IC50 = 59.1 +/- 2.6 MUM), 8 (IC50 = 51.8 +/- 3.4 MUM), and 9 (IC50 = 57.8 +/-
      3.2 MUM) were identified as more active against PC-3 cancer cell line than the
      substrate 1 (IC50 = 96.2 +/- 3.0 MUM). Metabolite 9 (IC50 = 2.8 +/- 0.2 MUM) also
      showed potent anticancer activity against HCT116 cancer cell line than the
      substrate 1 (IC50 = 3.1 +/- 3.2 MUM). In addition, compounds 1-7 showed no
      cytotoxicity against 3T3 normal cell line, while compounds 8 (IC50 = 74.6 +/- 3.7
      MUM), and 9 (IC50 = 62.1 +/- 1.2 MUM) were found to be weakly cytotoxic.

PMID- 29326587
TI  - HDAC2 and HDAC5 Up-Regulations Modulate Survivin and miR-125a-5p Expressions and
      Promote Hormone Therapy Resistance in Estrogen Receptor Positive Breast Cancer
      Cells.
AB  - Intrinsic or acquired resistance to hormone therapy is frequently reported in
      estrogen receptor positive (ER+) breast cancer patients. Even though
      dysregulations of histone deacetylases (HDACs) are known to promote cancer cells
      survival, the role of different HDACs in the induction of hormone therapy
      resistance in ER+ breast cancer remains unclear. Survivin is a well-known pro
      tumor survival molecule and miR-125a-5p is a recently discovered tumor
      suppressor. In this study, we found that ER+, hormone-independent, tamoxifen
      resistant MCF7-TamC3 cells exhibit increased expression of HDAC2, HDAC5, and
      survivin, but show decreased expression of miR-125a-5p, as compared to the
      parental tamoxifen-sensitive MCF7 breast cancer cells. Molecular down-regulations
      of HDAC2, HDAC5, and survivin, and ectopic over-expression of miR-125a-5p,
      increased the sensitivity of MCF7-TamC3 cells to estrogen deprivation and
      restored the sensitivity to tamoxifen. The same treatments also further increased
      the sensitivity to estrogen-deprivation in the ER+ hormone-dependent ZR-75-1
      breast cancer cells in vitro. Kaplan-Meier analysis and receiver operating
      characteristic curve analysis of expression cohorts of breast tumor showed that
      high HDAC2 and survivin, and low miR-125a-5p, expression levels correlate with
      poor relapse-free survival in endocrine therapy and tamoxifen-treated ER+ breast
      cancer patients. Further molecular analysis revealed that HDAC2 and HDAC5
      positively modulates the expression of survivin, and negatively regulates the
      expression miR-125a-5p, in ER+ MCF7, MCF7-TamC3, and ZR-75-1 breast cancer cells.
      These findings indicate that dysregulations of HDAC2 and HDAC5 promote the
      development of hormone independency and tamoxifen resistance in ERC breast cancer
      cells in part through expression regulation of survivin and miR-125a-5p.

PMID- 29326588
TI  - Age-Related Decrease in Male Extra-Striatal Adenosine A1 Receptors Measured
      Using11C-MPDX PET.
AB  - Adenosine A1 receptors (A1Rs) are widely distributed throughout the entire human
      brain, while adenosine A2A receptors (A2ARs) are present in dopamine-rich areas
      of the brain, such as the basal ganglia. A past study using autoradiography
      reported a reduced binding ability of A1R in the striatum of old rats. We
      developed positron emission tomography (PET) ligands for mapping the adenosine
      receptors and we successfully visualized the A1Rs using 8-dicyclopropylmethyl-1
      11C-methyl-3-propylxanthine (11C-MPDX). We previously reported that the density
      of A1Rs decreased with age in the human striatum, although we could not observe
      an age-related change in A2ARs. The aim of this study was to investigate the age
      related change of the density of A1Rs in the thalamus and cerebral cortices of
      healthy participants using 11C-MPDX PET. We recruited eight young (22.0 +/- 1.7
      years) and nine elderly healthy male volunteers (65.7 +/- 8.0 years). A dynamic
      series of decay-corrected PET scans was performed for 60 min starting with the
      injection of 11C-MPDX. We placed the circular regions of interest of 10 mm in
      diameter in 11C-MPDX PET images. The values for the binding potential (BPND) of
      11C-MPDX in the thalamus, and frontal, temporal, occipital, and parietal cortices
      were calculated using a graphical analysis, wherein the reference region was the
      cerebellum. BPND of 11C-MPDX was significantly lower in elderly participants than
      young participants in the thalamus, and frontal, temporal, occipital, and
      parietal cortices. In the human brain, we could observe the age-related decrease
      in the distribution of A1Rs.

PMID- 29326589
TI  - Increased Number of Circulating CD8/CD26 T Cells in the Blood of Duchenne
      Muscular Dystrophy Patients Is Associated with Augmented Binding of Adenosine
      Deaminase and Higher Muscular Strength Scores.
AB  - Duchenne muscular dystrophy (DMD) is an X-linked disorder that leads to cardiac
      and skeletal myopathy. The complex immune activation in boys with DMD is
      incompletely understood. To better understand the contribution of the immune
      system into the progression of DMD, we performed a systematic characterization of
      immune cell subpopulations obtained from peripheral blood of DMD subjects and
      control donors. We found that the number of CD8 cells expressing CD26 (also known
      as adenosine deaminase complexing protein 2) was increased in DMD subjects
      compared to control. No differences, however, were found in the levels of
      circulating factors associated with pro-inflammatory activation of CD8/CD26
      cells, such as tumor necrosis factor-alpha (TNFalpha), granzyme B, and interferon
      gamma (IFNgamma). The number of CD8/CD26 cells correlated directly with
      quantitative muscle testing (QMT) in DMD subjects. Since CD26 mediates binding of
      adenosine deaminase (ADA) to the T cell surface, we tested ADA-binding capacity
      of CD8/CD26 cells and the activity of bound ADA. We found that mononuclear cells
      (MNC) obtained from DMD subjects with an increased number of CD8/CD26 T cells had
      a greater capacity to bind ADA. In addition, these MNC demonstrated increased
      hydrolytic deamination of adenosine to inosine. Altogether, our data demonstrated
      that (1) an increased number of circulating CD8/CD26 T cells is associated with
      preservation of muscle strength in DMD subjects, and (2) CD8/CD26 T cells from
      DMD subjects mediated degradation of adenosine by adenosine deaminase. These
      results support a role for T cells in slowing the decline in skeletal muscle
      function, and a need for further investigation into contribution of CD8/CD26 T
      cells in the regulation of chronic inflammation associated with DMD.

PMID- 29326590
TI  - P2X4 Receptor in Silico and Electrophysiological Approaches Reveal Insights of
      Ivermectin and Zinc Allosteric Modulation.
AB  - Protein allosteric modulation is a pillar of metabolic regulatory mechanisms;
      this concept has been extended to include ion channel regulation. P2XRs are
      ligand-gated channels activated by extracellular ATP, sensitive to trace metals
      and other chemicals. By combining in silico calculations with
      electrophysiological recordings, we investigated the molecular basis of P2X4R
      modulation by Zn(II) and ivermectin, an antiparasite drug currently used in
      veterinary medicine. To this aim, docking studies, molecular dynamics simulations
      and non-bonded energy calculations for the P2X4R in the apo and holo states or in
      the presence of ivermectin and/or Zn(II) were accomplished. Based on the
      crystallized Danio rerio P2X4R, the rat P2X4R, P2X2R, and P2X7R structures were
      modeled, to determine ivermectin binding localization. Calculations revealed that
      its allosteric site is restricted to transmembrane domains of the P2X4R; the role
      of Y42 and W46 plus S341 and non-polar residues were revealed as essential, and
      are not present in the homologous P2X2R or P2X7R transmembrane domains. This
      finding was confirmed by preferential binding conformations and
      electrophysiological data, revealing P2X4R modulator specificity. Zn(II) acts in
      the P2X4R extracellular domain neighboring the SS3 bridge. Molecular dynamics in
      the different P2X4R states revealed allosterism-induced stability. Pore and
      lateral fenestration measurements of the P2X4R showed conformational changes in
      the presence of both modulators compatible with a larger opening of the
      extracellular vestibule. Electrophysiological studies demonstrated additive
      effects in the ATP-gated currents by joint applications of ivermectin plus
      Zn(II). The C132A P2X4R mutant was insensitive to Zn(II); but IVM caused a 4.9 +/
      0.7-fold increase in the ATP-evoked currents. Likewise, the simultaneous
      application of both modulators elicited a 7.1 +/- 1.7-fold increase in the ATP
      gated current. Moreover, the C126A P2X4R mutant evoked similar ATP-gated currents
      comparable to those of wild-type P2X4R. Finally, a P2X4/2R chimera did not
      respond to IVM but Zn(II) elicited a 2.7 +/- 0.6-fold increase in the ATP-gated
      current. The application of IVM plus Zn(II) evoked a 2.7 +/- 0.9-fold increase in
      the ATP-gated currents. In summary, allosteric modulators caused additive ATP
      gated currents; consistent with lateral fenestration enlargement. Energy
      calculations demonstrated a favorable transition of the holo receptor state
      following both allosteric modulators binding, as expected for allosteric
      interactions.

PMID- 29326592
TI  - Drug Repositioning in the Mirror of Patenting: Surveying and Mining Uncharted
      Territory.

PMID- 29326591
TI  - Association between Health-Related Quality of Life and Medication Adherence in
      Pulmonary Tuberculosis in South Africa.
AB  - Background: Health-related quality of life (HRQOL) and adherence to treatment are
      two often inter-related concepts that have implications for patient management
      and care. Tuberculosis (TB) and its treatment present a major public health
      concern in South Africa. The study aimed to evaluate the association between
      HRQOL and adherence in TB patients in South Africa. Methods: Four self-reported
      HRQOL and one self-reported adherence measures were used in an observational
      longitudinal multicentre study during 6-month standard TB treatment. These
      included the generic Short-Form 12 items (SF-12) and European Quality of Life 5
      dimensions 5 levels (EQ-5D-5L), the disease-specific St. George's Respiratory
      Questionnaire (SGRQ) and the condition-specific Hospital Anxiety and Depression
      Scale (HADS) for HRQOL. Adherence was measured by the Morisky Medication
      Adherence Scale 8 items (MMAS-8). The relationship between both concepts was
      examined in 131 patients using Spearman's rho correlations, and linear regression
      models. Results: HRQOL improved over 6-month TB treatment, whereas adherence mean
      scores stayed constant with participants attaining a medium average level. Around
      76% of patients reported to be high adherers and 24% were reporting a medium or
      low adherence. Associations between HRQOL and adherence were mainly weak. High
      adherence at treatment start was positively related to improvements in anxiety
      and depression after 6-month treatment. The overall improvement in pain and
      discomfort, and psychosocial health aspects over treatment time was positively,
      but weakly associated with adherence at 6 months of treatment. Conclusion: A
      positive relationship exists between adherence and HRQOL in TB in a South African
      setting, but this relationship was very weak, most likely because HRQOL is
      affected by a number of different factors and not limited to effects of
      adherence. Therefore, management of TB patients should, besides adequate drug
      treatment, address the specific mental and psychosocial needs.

PMID- 29326593
TI  - BOKP: A DNA Barcode Reference Library for Monitoring Herbal Drugs in the Korean
      Pharmacopeia.
AB  - Herbal drug authentication is an important task in traditional medicine; however,
      it is challenged by the limitations of traditional authentication methods and the
      lack of trained experts. DNA barcoding is conspicuous in almost all areas of the
      biological sciences and has already been added to the British pharmacopeia and
      Chinese pharmacopeia for routine herbal drug authentication. However, DNA
      barcoding for the Korean pharmacopeia still requires significant improvements.
      Here, we present a DNA barcode reference library for herbal drugs in the Korean
      pharmacopeia and developed a species identification engine named KP-IDE to
      facilitate the adoption of this DNA reference library for the herbal drug
      authentication. Using taxonomy records, specimen records, sequence records, and
      reference records, KP-IDE can identify an unknown specimen. Currently, there are
      6,777 taxonomy records, 1,054 specimen records, 30,744 sequence records (ITS2 and
      psbA-trnH) and 285 reference records. Moreover, 27 herbal drug materials were
      collected from the Seoul Yangnyeongsi herbal medicine market to give an example
      for real herbal drugs authentications. Our study demonstrates the prospects of
      the DNA barcode reference library for the Korean pharmacopeia and provides future
      directions for the use of DNA barcoding for authenticating herbal drugs listed in
      other modern pharmacopeias.

PMID- 29326594
TI  - The Gastric Ganglion of Octopus vulgaris: Preliminary Characterization of Gene-
      and Putative Neurochemical-Complexity, and the Effect of Aggregata octopiana
      Digestive Tract Infection on Gene Expression.
AB  - The gastric ganglion is the largest visceral ganglion in cephalopods. It is
      connected to the brain and is implicated in regulation of digestive tract
      functions. Here we have investigated the neurochemical complexity (through in
      silico gene expression analysis and immunohistochemistry) of the gastric ganglion
      in Octopus vulgaris and tested whether the expression of a selected number of
      genes was influenced by the magnitude of digestive tract parasitic infection by
      Aggregata octopiana. Novel evidence was obtained for putative peptide and non
      peptide neurotransmitters in the gastric ganglion: cephalotocin, corticotrophin
      releasing factor, FMRFamide, gamma amino butyric acid, 5-hydroxytryptamine,
      molluscan insulin-related peptide 3, peptide PRQFV-amide, and tachykinin-related
      peptide. Receptors for cholecystokininA and cholecystokininB, and orexin2 were
      also identified in this context for the first time. We report evidence for
      acetylcholine, dopamine, noradrenaline, octopamine, small cardioactive peptide
      related peptide, and receptors for cephalotocin and octopressin, confirming
      previous publications. The effects of Aggregata observed here extend those
      previously described by showing effects on the gastric ganglion; in animals with
      a higher level of infection, genes implicated in inflammation (NFkappaB, fascin,
      serpinB10 and the toll-like 3 receptor) increased their relative expression, but
      TNF-alpha gene expression was lower as was expression of other genes implicated
      in oxidative stress (i.e., superoxide dismutase, peroxiredoxin 6, and glutathione
      peroxidase). Elevated Aggregata levels in the octopuses corresponded to an
      increase in the expression of the cholecystokininA receptor and the small
      cardioactive peptide-related peptide. In contrast, we observed decreased relative
      expression of cephalotocin, dopamine beta-hydroxylase, peptide PRQFV-amide, and
      tachykinin-related peptide genes. A discussion is provided on (i) potential roles
      of the various molecules in food intake regulation and digestive tract motility
      control and (ii) the difference in relative gene expression in the gastric
      ganglion in octopus with relatively high and low parasitic loads and the
      similarities to changes in the enteric innervation of mammals with digestive
      tract parasites. Our results provide additional data to the described
      neurochemical complexity of O. vulgaris gastric ganglion.

PMID- 29326595
TI  - Thermo-Sensitive TRP Channels: Novel Targets for Treating Chemotherapy-Induced
      Peripheral Pain.
AB  - Abnormal Ca2+ channel physiology, expression levels, and hypersensitivity to heat
      have been implicated in several pain states following treatment with
      chemotherapeutic agents. As members of the Ca2+ permeable transient receptor
      potential (TRP), five of the channels (TRPV1-4 and TRPM2) are activated by
      different heat temperatures, and two of the channels (TRPA1 and TRPM8) are
      activated by cold temperature. Accumulating evidences indicates that antagonists
      of TRPA1 and TRPM8 may protect against cisplatin, oxaliplatin, and paclitaxel
      induced mitochondrial oxidative stress, inflammation, cold allodynia, and
      hyperalgesia. TRPV1 was responsible from the cisplatin-induced heat hyperalgesia
      and mechanical allodynia in the sensory neurons. TRPA1, TRPM8, and TRPV2 protein
      expression levels were mostly increased in the dorsal root (DRG) and trigeminal
      ganglia by these treatments. There is a debate on direct or oxaliplatin-induced
      oxidative cold stress dependent TRPA1 and TRPV4 activation in the DRG.
      Involvement of molecular pathways such as cysteine groups, glutathione
      metabolism, anandamide, cAMP, lipopolysaccharide, proteinase-activated receptor
      2, and mitogen-activated protein kinase were also indicated in the oxaliplatin
      and paclitaxel-induced cold allodynia. In this review, we summarized results of
      five temperature-regulated TRP channels (TRPA1, TRPM8, TRPV1, TRPV2, and TRPV4)
      as novel targets for treating chemotherapy-induced peripheral pain.

PMID- 29326596
TI  - An Integrated Analysis of miRNAs and Methylated Genes Encoding mRNAs and lncRNAs
      in Sheep Breeds with Different Fecundity.
AB  - In our previous study, we investigated the regulatory relationship between
      lncRNAs, miRNA, and mRNAs in an effort to shed light onto the regulatory
      mechanisms involved in sheep fecundity. As an extension of this study, here, we
      aimed to identify potential regulators of sheep fecundity using a genome-wide
      analysis of miRNAs and the methylated genes encoding mRNAs and lncRNAs in the
      ovaries of Dorset sheep (low fecundity) and Small Tail Han ewes (high fecundity)
      with the genotype BB (Han BB) and the genotype ++ (Han ++) by performing RNA-Seq
      and MeDIP-Seq analyses. Methylated coding-non-coding gene co-expression networks
      for Han and Dorset sheep were constructed using the methylated genes encoding the
      differentially expressed mRNAs and lncRNAs identified in this study. In the Han
      BB vs. Dorset comparison, the lncRNAs TTC26 and MYH15 had the largest degree.
      Similarly, the lncRNA NYAP1 had the largest degree in the Han ++ vs. Dorset
      comparison. None of the methylated genes encoding lncRNAs were co-expressed with
      the methylated genes encoding mRNAs in the Han BB vs. Han ++ comparison. The
      methylated genes encoding lncRNAs identified here may play a vital regulatory
      role in sheep breeding. Our results suggest that miRNAs might play a key role in
      sheep prolificacy by regulating target genes related to thyroid hormone
      synthesis, and methylated genes encoding lncRNAs associated with tight junctions
      might contribute to the high breeding rate in Han sheep. These findings may
      contribute to a deeper understanding of sheep prolificacy.

PMID- 29326597
TI  - Genome Wide Mapping of Peptidases in Rhodnius prolixus: Identification of
      Protease Gene Duplications, Horizontally Transferred Proteases and Analysis of
      Peptidase A1 Structures, with Considerations on Their Role in the Evolution of
      Hematophagy in Triatominae.
AB  - Triatominae is a subfamily of the order Hemiptera whose species are able to feed
      in the vertebrate blood (i.e., hematophagy). This feeding behavior presents a
      great physiological challenge to insects, especially in Hemipteran species with a
      digestion performed by lysosomal-like cathepsins instead of the more common
      trypsin-like enzymes. With the aim of having a deeper understanding of protease
      involvement in the evolutionary adaptation for hematophagy in Hemipterans, we
      screened peptidases in the Rhodnius prolixus genome and characterized them using
      common blast (NCBI) and conserved domain analyses (HMMER/blast manager software,
      FAT, plus PFAM database). We compared the results with available sequences from
      other hemipteran species and with 18 arthropod genomes present in the MEROPS
      database. Rhodnius prolixus contains at least 433 protease coding genes,
      belonging to 71 protease families. Seven peptidase families in R. prolixus
      presented higher gene numbers when compared to other arthropod genomes. Further
      analysis indicated that a gene expansion of the protease family A1 (Eukaryotic
      aspartyl protease, PF00026) might have played a major role in the adaptation to
      hematophagy since most of these peptidase genes seem to be recently acquired, are
      expressed in the gut and present putative secretory pathway signal peptides.
      Besides that, most R. prolixus A1 peptidases showed high frequencies of basic
      residues at the protein surface, a typical structural signature of Cathepsin D
      like proteins. Other peptidase families expanded in R. prolixus (i.e., C2 and
      M17) also presented significant differences between hematophagous (higher number
      of peptidases) and non-hematophagous species. This study also provides evidence
      for gene acquisition from microorganisms in some peptidase families in R.
      prolixus: (1) family M74 (murein endopeptidase), (2) family S29 (Hepatitis C
      virus NS3 protease), and (3) family S24 (repressor LexA). This study revealed new
      targets for studying the adaptation of these insects for digestion of blood meals
      and their competence as vectors of Chagas disease.

PMID- 29326599
TI  - Nfu1 Mediated ROS Removal Caused by Cd Stress in Tegillarca granosa.
AB  - The blood clam Tegillarca granosa, a eukaryotic bottom-dwelling bivalve species
      has a strong ability to tolerate and accumulate cadmium. In our previous study,
      Nfu1 (iron-sulfur cluster scaffold protein), which is involved in Fe-S cluster
      biogenesis, was shown to be significantly up-regulated under Cd stress, as
      determined by proteomic analysis. To investigate the function of Nfu1 in cadmium
      (Cd) detoxification, the function of blood clam Nfu1 (designated as Tg-Nfu1) was
      investigated by integrated molecular and protein approaches. The full-length cDNA
      of Tg-Nfu1 is 1167 bp and encodes a protein of 272 amino acid residues. The
      deduced Tg-Nfu1 protein is 30 kDa contains a conserved Nfu-N domain and a Fe-S
      cluster binding motif (C-X-X-C). qRT-PCR analysis revealed that Tg-Nfu1 was
      ubiquitously expressed in all examined tissues; it was up-regulated in the
      hepatopancreas and gill, and kept a high level from 9 to 24 h after Cd exposure
      (250 MUg/L). Western blot analysis further revealed that the Tg-Nfu1 protein was
      also highly expressed in the hepatopancreas and gill after 24 h of Cd stress.
      Further functional analysis showed that the production of ROS was increased and
      Cu/ZnSOD activity was inhibited in blood clam, treated with the specific Nfu1
      siRNA and Cd stress, respectively. These results suggest that Tg-Nfu1 could
      protect blood clam from oxidative damage caused by Cd stress.

PMID- 29326598
TI  - Connexins in the Central Nervous System: Physiological Traits and Neuroprotective
      Targets.
AB  - Cell-to-cell interaction and cell-to-extracellular environment communication are
      emerging as new therapeutic targets in neurodegenerative disorders. Dynamic
      expression of connexins leads to distinctive hemichannels and gap junctions,
      characterized by cell-specific conduction, exchange of stimuli or metabolites,
      and particular channel functions. Herein, we briefly reviewed classical
      physiological traits and functions of connexins, hemichannels, and gap junctions,
      in order to discuss the controversial role of these proteins and their mediated
      interactions during neuroprotection, with a particular focus on Cx43-based
      channels. We pointed out the contribution of connexins in neural cells
      populations during neurodegenerative processes to explore potential
      neuroprotective therapeutic applications.

PMID- 29326600
TI  - Exercise-Induced Hypertrophic and Oxidative Signaling Pathways and Myokine
      Expression in Fast Muscle of Adult Zebrafish.
AB  - Skeletal muscle is a plastic tissue that undergoes cellular and metabolic
      adaptations under conditions of increased contractile activity such as exercise.
      Using adult zebrafish as an exercise model, we previously demonstrated that
      swimming training stimulates hypertrophy and vascularization of fast muscle
      fibers, consistent with the known muscle growth-promoting effects of exercise and
      with the resulting increased aerobic capacity of this tissue. Here we
      investigated the potential involvement of factors and signaling mechanisms that
      could be responsible for exercise-induced fast muscle remodeling in adult
      zebrafish. By subjecting zebrafish to swimming-induced exercise, we observed an
      increase in the activity of mammalian target of rapamycin (mTOR) and Mef2 protein
      levels in fast muscle. We also observed an increase in the protein levels of the
      mitotic marker phosphorylated histone H3 that correlated with an increase in the
      protein expression levels of Pax7, a satellite-like cell marker. Furthermore, the
      activity of AMP-activated protein kinase (AMPK) was also increased by exercise,
      in parallel with an increase in the mRNA expression levels of pgc1alpha and also
      of pparda, a beta-oxidation marker. Changes in the mRNA expression levels of slow
      and fast myosin markers further supported the notion of an exercise-induced
      aerobic phenotype in zebrafish fast muscle. The mRNA expression levels of il6,
      il6r, apln, aplnra and aplnrb, sparc, decorin and igf1, myokines known in mammals
      to be produced in response to exercise and to signal through mTOR/AMPK pathways,
      among others, were increased in fast muscle of exercised zebrafish. These results
      support the notion that exercise increases skeletal muscle growth and myogenesis
      in adult zebrafish through the coordinated activation of the mTOR-MEF2 and AMPK
      PGC1alpha signaling pathways. These results, coupled with altered expression of
      markers for oxidative metabolism and fast-to-slow fiber-type switch, also suggest
      improved aerobic capacity as a result of swimming-induced exercise. Finally, the
      induction of myokine expression by swimming-induced exercise support the
      hypothesis that these myokines may have been produced and secreted by the
      exercised zebrafish muscle and acted on fast muscle cells to promote metabolic
      remodeling. These results support the use of zebrafish as a suitable model for
      studies on muscle remodeling in vertebrates, including humans.

PMID- 29326601
TI  - The Role of TonB Gene in Edwardsiella ictaluri Virulence.
AB  - Edwardsiella ictaluri is a Gram-negative facultative intracellular pathogen that
      causes enteric septicemia in catfish (ESC). Stress factors including poor water
      quality, poor diet, rough handling, overcrowding, and water temperature
      fluctuations increase fish susceptibility to ESC. The TonB energy transducing
      system (TonB-ExbB-ExbD) and TonB-dependent transporters of Gram-negative bacteria
      support active transport of scarce resources including iron, an essential
      micronutrient for bacterial virulence. Deletion of the tonB gene attenuates
      virulence in several pathogenic bacteria. In the current study, the role of TonB
      (NT01EI_RS07425) in iron acquisition and E. ictaluri virulence were investigated.
      To accomplish this, the E. ictaluri tonB gene was in-frame deleted. Growth
      kinetics, iron utilization, and virulence of the EiDeltatonB mutant were
      determined. Loss of TonB caused a significant reduction in bacterial growth in
      iron-depleted medium (p > 0.05). The EiDeltatonB mutant grew similarly to wild
      type E. ictaluri when ferric iron was added to the iron-depleted medium. The
      EiDeltatonB mutant was significantly attenuated in catfish compared with the
      parent strain (21.69 vs. 46.91% mortality). Catfish surviving infection with
      EiDeltatonB had significant protection against ESC compared with naive fish (100
      vs. 40.47% survival). These findings indicate that TonB participates in
      pathogenesis of ESC and is an important E. ictaluri virulence factor.

PMID- 29326602
TI  - Physical Capacity and Energy Expenditure of Cavers.
AB  - Caves are an extreme environment for humans because of the high humidity, mud,
      darkness, and slippery conditions. Explorations can last many hours or even days,
      and require extensive climbing and ropework. Very little is known about the
      physical capacity of cavers and their energy expenditure (EE) during caving. The
      physical capacity of 17 (7 females) expert cavers (age 43.9 +/- 7.3 years) was
      assessed during an incremental cycle-ergometer test (IET) with gas exchange
      analysis. Moreover, a wearable metabolic band (Armband Fit Core) was used to
      estimate their EE during caving. In terms of physical capacity, the IET showed
      that cavers had a maximum oxygen uptake (VO2max) of 2,248.7 +/- 657.8 ml.min-1
      (i.e., 32.4 +/- 6.4 ml.kg-1.min-1), while anaerobic threshold (AT) occurred on
      average at 74.5% of VO2max. Results from caving sessions provided an average time
      spent in cave of 9.4 +/- 1.2 h while the average EE was 268.8 +/- 54.8 kcal.h-1,
      which corresponded to about 40% of VO2max measured during IET. A mean distance of
      10.6 +/- 2.2 km was covered by subjects. Data from the present investigation
      provide evidence that cavers have a level of aerobic physical capacity only
      slightly higher than that of sedentary people, thereby suggesting that a high
      aerobic fitness is not needed by cavers. Moreover, during caving the EE was on
      average well below the level of AT. However, in absolute terms, the total EE was
      elevated (i.e., 2,672.3 +/- 576 kcal in total) due to the long time spent in
      caving.

PMID- 29326603
TI  - The Training Characteristics of the World's Most Successful Female Cross-Country
      Skier.
AB  - The main aim of this study was to investigate the training characteristics of the
      most successful female cross-country skier ever during the best period of her
      career. The participant won six gold medals at the Olympic Games, 18 gold medals
      at the World Championship, and 110 World Cup victories. Day-to-day training diary
      data, interviews, and physiological tests were analyzed. Training data was
      systemized by training form (endurance, strength, and speed), intensity [low-
      (LIT), moderate- (MIT), and high-intensity training (HIT)], and mode (running,
      cycling, and skiing/roller skiing), followed by a division into different
      periodization phases. Specific sessions utilized in the various periodization
      periods and the day-to-day periodization of training, in connection with altitude
      camps and tapering toward major championships, were also analyzed. Following a 12
      year nonlinear increase in training load, the annual training volume during the
      five consecutive successful years stabilized at 937 +/- 25 h, distributed across
      543 +/- 9 sessions. During these 5 years, total training time was distributed as
      90.6% endurance-, 8.0% strength-, and 1.4% speed-training, with endurance
      training time consisting of 92.3 +/- 0.3% LIT, 2.9 +/- 0.5% MIT, and 4.8 +/- 0.5%
      HIT. Total LIT-time consisted of 21% warm-up, 14% sessions <90 min, and 65% long
      duration sessions >90 min. While the total number of LIT sessions remained stable
      across phases (32 sessions), total LIT-time was reduced from GP (76 h/month) to
      SP (68 h/month) and CP (55 h/month). MIT-time decreased from GP (2.8 h/month) to
      SP (2.2 h/month) and CP (1 h/month). HIT-time increased from GP (2.8 h/month) to
      SP (3.2 h/month) and CP (4.7 h/month). Altitude training accounted for 18-25% of
      annual training volume and performed across relatively short training camps (<=16
      days) with a clear reduction of HIT training, but increased total and LIT volume
      compared to sea-level training. Training before international championships
      included a 2-week increase in LIT and strength volume followed by a gradual
      reduction of training volume and increased HIT during the last week. This study
      provides unique data on the world's most successful female cross-country skier's
      long-term training process, including novel information about the distribution of
      and interplay between sessions of different forms, intensities, and exercise
      modes throughout the annual season.

PMID- 29326604
TI  - A Shift in the Thermoregulatory Curve as a Result of Selection for High Activity
      Related Aerobic Metabolism.
AB  - According to the "aerobic capacity model," endothermy in birds and mammals
      evolved as a result of natural selection favoring increased persistent locomotor
      activity, fuelled by aerobic metabolism. However, this also increased energy
      expenditure even during rest, with the lowest metabolic rates occurring in the
      thermoneutral zone (TNZ) and increasing at ambient temperatures (Ta) below and
      above this range, depicted by the thermoregulatory curve. In our experimental
      evolution system, four lines of bank voles (Myodes glareolus) have been selected
      for high swim-induced aerobic metabolism and four unselected lines have been
      maintained as a control. In addition to a 50% higher rate of oxygen consumption
      during swimming, the selected lines have also evolved a 7.3% higher mass-adjusted
      basal metabolic rate. Therefore, we asked whether voles from selected lines would
      also display a shift in the thermoregulatory curve and an increased body
      temperature (Tb) during exposure to high Ta. To test these hypotheses we measured
      the RMR and Tb of selected and control voles at Ta from 10 to 34 degrees C. As
      expected, RMR within and around the TNZ was higher in selected lines. Further,
      the Tb of selected lines within the TNZ was greater than the Tb of control lines,
      particularly at the maximum measured Ta of 34 degrees C, suggesting that selected
      voles are more prone to hyperthermia. Interestingly, our results revealed that
      while the slope of the thermoregulatory curve below the lower critical
      temperature (LCT) is significantly lower in the selected lines, the LCT (26.1
      degrees C) does not differ. Importantly, selected voles also evolved a higher
      maximum thermogenesis, but thermal conductance did not increase. As a
      consequence, the minimum tolerated temperature, calculated from an extrapolation
      of the thermoregulatory curve, is 8.4 degrees C lower in selected (-28.6 degrees
      C) than in control lines (-20.2 degrees C). Thus, selection for high aerobic
      exercise performance, even though operating under thermally neutral conditions,
      has resulted in the evolution of increased cold tolerance, which, under natural
      conditions, could allow voles to inhabit colder environments. Further, the
      results of the current experiment support the assumptions of the aerobic capacity
      model of the evolution of endothermy.

PMID- 29326605
TI  - Variability in Tidal Volume Affects Lung and Cardiovascular Function
      Differentially in a Rat Model of Experimental Emphysema.
AB  - In experimental elastase-induced emphysema, mechanical ventilation with variable
      tidal volumes (VT) set to 30% coefficient of variation (CV) may result in more
      homogenous ventilation distribution, but might also impair right heart function.
      We hypothesized that a different CV setting could improve both lung and
      cardiovascular function. Therefore, we investigated the effects of different
      levels of VT variability on cardiorespiratory function, lung histology, and gene
      expression of biomarkers associated with inflammation, fibrogenesis, epithelial
      cell damage, and mechanical cell stress in this emphysema model. Wistar rats (n =
      35) received repeated intratracheal instillation of porcine pancreatic elastase
      to induce emphysema. Seven animals were not ventilated and served as controls
      (NV). Twenty-eight animals were anesthetized and assigned to mechanical
      ventilation with a VT CV of 0% (BASELINE). After data collection, animals (n =
      7/group) were randomly allocated to VT CVs of 0% (VV0); 15% (VV15); 22.5%
      (VV22.5); or 30% (VV30). In all groups, mean VT was 6 mL/kg and positive end
      expiratory pressure was 3 cmH2O. Respiratory system mechanics and cardiac
      function (by echocardiography) were assessed continuously for 2 h (END). Lung
      histology and molecular biology were measured post-mortem. VV22.5 and VV30
      decreased respiratory system elastance, while VV15 had no effect. VV0, VV15, and
      VV22.5, but not VV30, increased pulmonary acceleration time to pulmonary ejection
      time ratio. VV22.5 decreased the central moment of the mean linear intercept (D2
      of Lm) while increasing the homogeneity index (1/beta) compared to NV (77 +/- 8
      MUm vs. 152 +/- 45 MUm; 0.85 +/- 0.06 vs. 0.66 +/- 0.13, p < 0.05 for both).
      Compared to NV, VV30 was associated with higher interleukin-6 expression.
      Cytokine-induced neutrophil chemoattractant-1 expression was higher in all
      groups, except VV22.5, compared to NV. IL-1beta expression was lower in VV22.5
      and VV30 compared to VV0. IL-10 expression was higher in VV22.5 than NV. Club
      cell protein 16 expression was higher in VV22.5 than VV0. SP-D expression was
      higher in VV30 than NV, while SP-C was higher in VV30 and VV22.5 than VV0. In
      conclusion, VV22.5 improved respiratory system elastance and homogeneity of
      airspace enlargement, mitigated inflammation and epithelial cell damage, while
      avoiding impairment of right cardiac function in experimental elastase-induced
      emphysema.

PMID- 29326606
TI  - ACTN3: More than Just a Gene for Speed.
AB  - Over the last couple of decades, research has focused on attempting to understand
      the genetic influence on sports performance. This has led to the identification
      of a number of candidate genes which may help differentiate between elite and non
      elite athletes. One of the most promising genes in that regard is ACTN3, which
      has commonly been referred to as "a gene for speed". Recent research has examined
      the influence of this gene on other performance phenotypes, including exercise
      adaptation, exercise recovery, and sporting injury risk. In this review, we
      identified 19 studies exploring these phenotypes. Whilst there was large
      variation in the results of these studies, as well as extremely heterogeneous
      cohorts, there is overall a tentative consensus that ACTN3 genotype can impact
      the phenotypes of interest. In particular, the R allele of a common polymorphism
      (R577X) is associated with enhanced improvements in strength, protection from
      eccentric training-induced muscle damage, and sports injury. This illustrates
      that ACTN3 is more than just a gene for speed, with potentially wide-ranging
      influence on muscle function, knowledge of which may aid in the future
      personalization of exercise training programmes.

PMID- 29326607
TI  - CYP1A1 Ile462Val Polymorphism Is Associated with Cervical Cancer Risk in
      Caucasians Not Asians: A Meta-Analysis.
AB  - Objective: Previous studies have reported that Ile462Val polymorphism in the gene
      Cytochrome P450 1A1 (CYP1A1) is associated with the risk of cervical cancer, but
      inconsistent results have emerged. Hence, we performed this updated and
      cumulative meta-analysis to ascertain a more accurate association between CYP1A1
      Ile462Val polymorphism and risk of cervical cancer. Methods: Studies involving
      the CYP1A1 Ile462Val polymorphism associated with cervical cancer risk were
      searched from the databases of PubMed, Scopus, ScienceDirect, and Chinese
      National Knowledge Infrastructure (CNKI). The strength of correlation was
      evaluated through calculating summary odds ratios (ORs) with the corresponding
      95% confidence intervals (95% CIs). Subgroup analyses according to ethnicity,
      source of control and HWE were completed to further explore specific association
      between the polymorphism and the cancer risk. Results: Altogether, 11 eligible
      case-control studies were ultimately encompassed into the current meta-analysis,
      with 1,932 patients and 2,039 healthy controls. The total analysis revealed a
      borderline relationship between CYP1A1 Ile462Val polymorphism and cervical cancer
      risk in general population. Interestingly, after subgroup analyses based on
      ethnicity and source of control, the polymorphism increased the susceptibility of
      cervical cancer in Caucasian (G vs. A: OR = 1.97, 95% CI = 1.24-3.13; GG vs. AA:
      OR = 3 .24, 95% CI = 1.24-8.46; GA vs. AA: OR = 1.62, 95% CI = 1.25-2.10; GA+GG
      vs. AA: OR = 1.68, 95% CI = 1.16-2.43; GG vs. AA+GA: OR = 2.73, 95% CI = 1.05
      7.10) and population-based (G vs. A: OR = 1.49, 95% CI = 1.10-2.02; GA vs. AA: OR
      = 1.41, 95% CI = 1.20-1.67; GA+GG vs. AA: OR = 1.40, 95% CI = 1.19-1.64) groups.
      Conclusion: The CYP1A1 Ile462Val polymorphism may enhance the susceptibility to
      cervical cancer in Caucasian females.

PMID- 29326608
TI  - Identification and Expression Patterns of Putative Diversified Carboxylesterases
      in the Tea Geometrid Ectropis obliqua Prout.
AB  - Carboxylesterases (CXEs) belong to a family of metabolic enzymes. Some CXEs act
      as odorant-degrading enzymes (ODEs), which are reportedly highly expressed in
      insect olfactory organs and participate in the rapid deactivation of ester
      pheromone components and plant volatiles. The tea geometrid Ectropis obliqua
      Prout produces sex pheromones consisting of non-ester functional compounds but
      relies heavily on acetic ester plant volatiles to search for host plants and
      locate oviposition sites. However, studies characterizing putative candidate ODEs
      in this important tea plant pest are still relatively scarce. In the present
      study, we identified 35 candidate EoblCXE genes from E. obliqua chemosensory
      organs based on previously obtained transcriptomic data. The deduced amino acid
      sequences possessed the typical characteristics of the insect CXE family,
      including oxyanion hole residues, the Ser-Glu-His catalytic triad, and the Ser
      active included in the conserved pentapeptide characteristic of esterases, Gly-X
      Ser-X-Gly. Phylogenetic analyses revealed that the EoblCXEs were diverse,
      belonging to several different insect esterase clades. Tissue- and sex-related
      expression patterns were studied via reverse-transcription and quantitative real
      time polymerase chain reaction analyses (RT- and qRT-PCR). The results showed
      that 35 EoblCXE genes presented a diversified expression profile; among these, 12
      EoblCXEs appeared to be antenna-biased, two EoblCXEs were non-chemosensory organ
      biased, 12 EoblCXEs were ubiquitous, and nine EoblCXEs showed heterogeneous
      expression levels among different tissues. Intriguingly, two EoblCXE genes,
      EoblCXE7 and EoblCXE13, were not only strongly localized to antennal sensilla
      tuned to odorants, such as the sensilla trichodea (Str I and II) and sensilla
      basiconica (Sba), but were also expressed in the putative gustatory sensilla
      styloconica (Sst), indicating that these two CXEs might play multiple
      physiological roles in the E. obliqua chemosensory processing system. This study
      provides the first elucidation of CXEs in the chemosensory system of a geometrid
      moth species and will enable a more comprehensive understanding of the functions
      of insect CXEs across lepidopteran species.

PMID- 29326609
TI  - A Biomarker to Differentiate between Primary and Cocaine-Induced Major Depression
      in Cocaine Use Disorder: The Role of Platelet IRAS/Nischarin (I1-Imidazoline
      Receptor).
AB  - The association of cocaine use disorder (CUD) and comorbid major depressive
      disorder (MDD; CUD/MDD) is characterized by high prevalence and poor treatment
      outcomes. CUD/MDD may be primary (primary MDD) or cocaine-induced (CUD-induced
      MDD). Specific biomarkers are needed to improve diagnoses and therapeutic
      approaches in this dual pathology. Platelet biomarkers [5-HT2A receptor and
      imidazoline receptor antisera selected (IRAS)/nischarin] were assessed by Western
      blot in subjects with CUD and primary MDD (n = 16) or CUD-induced MDD (n = 9;
      antidepressant free, AD-; antidepressant treated, AD+) and controls (n = 10) at
      basal level and/or after acute tryptophan depletion (ATD). Basal platelet 5-HT2A
      receptor (monomer) was reduced in comorbid CUD/MDD subjects (all patients: 43%)
      compared to healthy controls, and this down-regulation was independent of AD
      medication (decreases in AD-: 47%, and in AD+: 40%). No basal differences were
      found for IRAS/nischarin contents in AD+ and AD- comorbid CUD/MDD subjects. The
      comparison of IRAS/nischarin in the different subject groups during/after ATD
      showed opposite modulations (i.e., increases and decreases) in response to low
      plasma tryptophan levels with significant differences discriminating between the
      subgroups of CUD with primary MDD and CUD-induced MDD. These specific alterations
      suggested that platelet IRAS/nischarin might be useful as a biomarker to
      discriminate between primary and CUD-induced MDD in this dual pathology.

PMID- 29326610
TI  - Posttraumatic Stress Disorder and Related Disorders among Female Yazidi Refugees
      following Islamic State of Iraq and Syria Attacks-A Case Series and Mini-Review.
AB  - Following the severe attacks by the so-called "Islamic State of Iraq and Syria"
      on the Yazidi population, which started in summer 2014, the state government of
      Baden-Wurttemberg, Germany, funded a Special-Quota Project to bring 1,000 very
      ill or left-behind women and children who were being held hostage to 22 cities
      and towns in Baden-Wurttemberg to receive integrated care. Here, we report for
      the first time on the cases of four Yazidi women living in Ulm, Germany, focusing
      on the clinically observed and psychometrically assessed mental phenomena or
      disorders. Our primary aim was to explore what International Classification of
      Diseases, 10th Revision diagnoses are present in this population. Although highly
      traumatized, these women were suffering primarily from adjustment disorder rather
      than posttraumatic stress disorder according to official classification systems.
      Despite their symptoms of depression and anxiety, the women's responses to self
      assessment questionnaires provided no evidence of compulsion, somatization, or
      eating disorders. The results suggest that further investigation of the
      individual-level effects of rape and torture, as well the historic, systemic, and
      collective effects, e.g., on families and societies, is required.

PMID- 29326612
TI  - Dysfunctional Prefrontal Function Is Associated with Impulsivity in People with
      Internet Gaming Disorder during a Delay Discounting Task.
AB  - Internet gaming disorder (IGD), defined as the persistent use of online games
      with ignorance of adverse consequences, has increasingly raised widespread public
      concerns. This study aimed at elucidating the precise mechanisms underlying IGD
      by comparing intertemporal decision-making process between 18 IGD participants
      and 21 matched healthy controls (HCs). Both behavioral and fMRI data were
      recorded from a delay discounting task. At the behavioral level, the IGD showed a
      higher discount rate k than HC; and in IGD group, both the reaction time (delay -
      immediate) and the discount rate k were significantly positively correlated with
      the severity of IGD. At the neural level, the IGD exhibited reduced brain
      activations in the dorsolateral prefrontal cortex and bilateral inferior frontal
      gyrus compared to HC during performing delay trials relative to immediate ones.
      Taken together, the results suggested that IGD showed deficits in making
      decisions and tended to pursuit immediate satisfaction. The underlying mechanism
      arises from the deficient ability in evaluating between delayed reward and
      immediate satisfaction, and the impaired ability in impulse inhibition, which may
      be associated with the dysfunction of the prefrontal activation. These might be
      the reason why IGD continue playing online games in spite of facing severe
      negative consequences.

PMID- 29326613
TI  - French Translation and Validation of Three Scales Evaluating Stigma in Mental
      Health.
AB  - Objective: The concept of stigma refers to problems of knowledge (ignorance),
      attitudes (prejudice), and behavior (discrimination). Stigma may hinder access to
      care, housing, and work. In the context of implementation of programs such as
      "housing first" or "individual placement and support" in French speaking regions,
      validated instruments measuring stigma are necessary. "Attitudes to Mental
      Illness 2011" is a questionnaire that includes three scales measuring stigma
      through these three dimensions. This study aimed to translate, adapt, and
      validate these three scales in French. Methods: The "Attitudes to Mental Illness
      2011" questionnaire was translated into French and back-translated into English
      by an expert. Two hundred and sixty-eight nursing students completed the
      questionnaire. Content validity, face validity, internal validity, and convergent
      validity were assessed. Long-term reliability was also estimated over a three
      month period. Results: Experts and participants found that the questionnaire's
      content validity and face validity were appropriate. The internal validities of
      the three scales were also considered adequate. Convergent validity indicated
      that the scales did indeed measure what they were supposed to. Long-term
      stability estimates were moderate; this pattern of results suggested that the
      construct targeted by the three scales is adequately measured but does not
      necessarily represent stable and enduring traits. Conclusion: Because of their
      good psychometric properties, these three scales can be used in French, either
      separately, to measure one specific dimension of stigma, or together, to assess
      stigma in its three dimensions. This would seem of paramount importance in
      evaluating campaigns against stigma since it allows measures to be adapted
      according to campaign goals and the target population.

PMID- 29326611
TI  - Type 2 Neural Progenitor Cell Activation Drives Reactive Neurogenesis after Binge
      Like Alcohol Exposure in Adolescent Male Rats.
AB  - Excessive alcohol consumption during adolescence remains a significant health
      concern as alcohol drinking during adolescence increases the likelihood of an
      alcohol use disorder in adulthood by fourfold. Binge drinking in adolescence is a
      particular problem as binge-pattern consumption is the biggest predictor of
      neurodegeneration from alcohol and adolescents are particularly susceptible to
      the damaging effects of alcohol. The adolescent hippocampus, in particular, is
      highly susceptible to alcohol-induced structural and functional effects,
      including volume and neuron loss. However, hippocampal structure and function may
      recover with abstinence and, like in adults, a reactive burst in hippocampal
      neurogenesis in abstinence may contribute to that recovery. As the mechanism of
      this reactive neurogenesis is not known, the current study investigated potential
      mechanisms of reactive neurogenesis in binge alcohol exposure in adolescent, male
      rats. In a screen for cell cycle perturbation, a dramatic increase in the number
      of cells in all phases of the cycle was observed at 7 days following binge
      ethanol exposure as compared to controls. However, the proportion of cells in
      each phase was not different between ethanol-exposed rats and controls,
      indicating that cell cycle dynamics are not responsible for the reactive burst in
      neurogenesis. Instead, the marked increase in hippocampal proliferation was shown
      to be due to a twofold increase in proliferating progenitor cells, specifically
      an increase in cells colabeled with the progenitor cell marker Sox2 and S-phase
      (proliferation) marker, BrdU, in ethanol-exposed rats. To further characterize
      the individual subtypes of neural progenitor cells (NPCs) affected by adolescent
      binge ethanol exposure, a fluorescent quadruple labeling technique was utilized
      to differentiate type 1, 2a, 2b, and 3 progenitor cells simultaneously. At one
      week into abstinence, animals in the ethanol exposure groups had an increase in
      proliferating type 2 (intermediate progenitors) and type 3 (neuroblast)
      progenitors but not type 1 neural stem cells. These results together suggest that
      activation of type 2 NPCs out of quiescence is likely the primary mechanism for
      reactive hippocampal neurogenesis following adolescent alcohol exposure.

PMID- 29326615
TI  - Parenting, Peer Relationships, Academic Self-efficacy, and Academic Achievement:
      Direct and Mediating Effects.
AB  - The aim of the present study is to analyze the relation between authoritative and
      permissive parenting styles with the kinds of adolescent peer relationships
      (attachment, victimization, or aggression), and of the latter ones, in turn, with
      academic self-efficacy, and academic performance, in three waves that range from
      the early-mid adolescence to late adolescence. Five hundred Spanish adolescents,
      of both sexes, participated in a three-wave longitudinal study in Valencia,
      Spain. In the first wave, adolescents were either in the third year of secondary
      school or the fourth year of secondary school. The mean age in the first wave was
      14.70 (SD = 0.68; range = 13-16 years). Child Report of Parental Behavior
      Inventory (Schaefer, 1965; Samper et al., 2006), Peer Attachment (from the
      Inventory of Parent and Peer Attachment by Armsden and Greenberg, 1987),
      Victimization (from the Kit at School, Buhs et al., 2010), Physical and Verbal
      Aggression Scale (Caprara and Pastorelli, 1993; Del Barrio et al., 2001), items
      of academic self-efficacy, and items of academic performance were administered.
      Structural equations modeling-path analysis was employed to explore the proposed
      models. The results indicated that parenting styles relate to the way the
      adolescents develops attachments to their peers and to academic self-efficacy.
      The mother's permissive style is an important positive predictor of aggressive
      behavior and a negative predictor of attachment to their peers. At the end, peer
      relations and academic self-efficacy are mediator variables between parenting
      styles and academic performance.

PMID- 29326614
TI  - Prediction Analysis for Transition to Schizophrenia in Individuals at Clinical
      High Risk for Psychosis: The Relationship of DAO, DAOA, and NRG1 Variants with
      Negative Symptoms and Cognitive Deficits.
AB  - Schizophrenia is characterized by positive and negative symptoms and cognitive
      dysfunction. The glutamate hypothesis of schizophrenia has been hypothesized to
      explain the negative symptoms and cognitive deficits better than the dopamine
      hypothesis alone. Therefore, we aimed to evaluate whether glutamatergic variants
      such as d-amino acid oxidase (DAO), DAO activator (DAOA)/G72, and neuregulin 1
      (NRG1) single-nucleotide polymorphisms (SNPs) and their mRNA levels predicted (i)
      transition to schizophrenia spectrum disorders and (ii) research domain criteria
      (RDoC) domains, mainly negative valence and cognitive systems. In a 3-year
      prospective study cohort of 185 individuals (age: 13-35 years) at high risk and
      ultra-high risk (UHR) for psychosis, we assessed DAO (rs3918347, rs4623951), DAOA
      (rs778293, rs3916971, rs746187), and NRG1 (rs10503929) SNPs and their mRNA
      expression. Furthermore, we investigated their association with RDoC domains,
      mainly negative valence (e.g., anxiety, hopelessness) and cognitive (e.g.,
      perception disturbances, disorganized symptoms) systems. NRG1 rs10503929 CC + CT
      versus TT genotype carriers experienced significantly more disorganized symptoms.
      DAOA rs746187 CC versus CT + TT genotype, DAOA rs3916971 TT versus TC + CC
      genotype, and DAO rs3918347 GA + AA versus GG genotype carriers experienced
      nominally more hopelessness, visual perception disturbances, and auditory
      perception disturbances, respectively. The schizophrenia risk G-allele of DAO
      rs3918347 nominally increased risk for those UHR individuals with attenuated
      positive symptoms syndrome. No association between DAO, DAOA, NRG1 SNPs, and
      conversion to schizophrenia spectrum disorders was observed. Our findings suggest
      that DAO, DAOA, and NRG1 polymorphisms might influence both RDoC negative valence
      and cognitive systems, but not transition to schizophrenia spectrum disorders.

PMID- 29326616
TI  - Chilean Adaptation and Validation of the Early Adolescent Temperament
      Questionnaire-Revised Version.
AB  - The aim of this study was to develop an adapted version of the Early Adolescent
      Temperament Questionnaire-Revised (EATQ-R) that would be valid and reliable for
      assessing temperament and its components in Chileans between 12 and 18 years of
      age. Originally, Ellis and Rothbart (2001) developed this questionnaire (EATQ-R)
      to be used in North American adolescents. For the study in Chile, a translation
      protocol was developed, to maintain the original instrument's cultural and
      linguistic equivalence in the adapted version. Psychometric properties of the
      EATQ-R, such as factor structure, internal consistency, and convergent validity,
      were also assessed. The adaption and validation was carried out in two stages,
      with two different studies. The first study, which included 612 adolescent
      students from educational establishments in the cities of Santiago and
      Concepcion, Chile, developed the Chilean version of the 83-item EATQ-R, which has
      13 dimensions, belonging to 4 theoretical factors with adequate internal
      consistency (Cronbach's alpha = 0.79-0.82). The second study assessed the
      questionnaire's convergent validity, through its application to 973 adolescent
      students in Santiago. Results show that the effortful control subscale was
      significantly inversely related to indicators of adolescent maladjustment, such
      as substance abuse and behavioral problems. In addition, it was directly
      associated with indicators of self-concept, including self-esteem and self
      efficacy. The opposite pattern was observed when considering negative affect.
      These findings coincide with current knowledge on the relationship between
      temperament and adjustment in adolescents.

PMID- 29326617
TI  - Enrichment Effects of Gestures and Pictures on Abstract Words in a Second
      Language.
AB  - Laboratory research has demonstrated that multisensory enrichment promotes verbal
      learning in a foreign language (L2). Enrichment can be done in various ways,
      e.g., by adding a picture that illustrates the L2 word's meaning or by the
      learner performing a gesture to the word (enactment). Most studies have tested
      enrichment on concrete but not on abstract words. Unlike concrete words, the
      representation of abstract words is deprived of sensory-motor features. This has
      been addressed as one of the reasons why abstract words are difficult to
      remember. Here, we ask whether a brief enrichment training by means of pictures
      and by self-performed gestures also enhances the memorability of abstract words
      in L2. Further, we explore which of these two enrichment strategies is more
      effective. Twenty young adults learned 30 novel abstract words in L2 according to
      three encoding conditions: (1) reading, (2) reading and pairing the novel word to
      a picture, and (3) reading and enacting the word by means of a gesture. We
      measured memory performance in free and cued recall tests, as well as in a visual
      recognition task. Words encoded with gestures were better remembered in the free
      recall in the native language (L1). When recognizing the novel words,
      participants made less errors for words encoded with gestures compared to words
      encoded with pictures. The reaction times in the recognition task did not differ
      across conditions. The present findings support, even if only partially, the idea
      that enactment promotes learning of abstract words and that it is superior to
      enrichment by means of pictures even after short training.

PMID- 29326618
TI  - The Leadership Lab for Women: Advancing and Retaining Women in STEM through
      Professional Development.
AB  - Innovative professional development approaches are needed to address the ongoing
      lack of women leaders in science, technology, engineering, and math (STEM)
      careers. Developed from the research on women who persist in engineering and
      computing professions and essential elements of women's leadership development,
      the Leadership Lab for Women in STEM Program was launched in 2014. The Leadership
      Lab was created as a research-based leadership development program, offering 360
      degree feedback, coaching, and practical strategies aimed at increasing the
      advancement and retention of women in the STEM professions. The goal is to
      provide women with knowledge, tools and a supportive learning environment to help
      them navigate, achieve, flourish, and catalyze organizational change in male
      dominated and technology-driven organizations. This article describes the
      importance of creating unique development experiences for women in STEM fields,
      the genesis of the Leadership Lab, the design and content of the program, and the
      outcomes for the participants.

PMID- 29326619
TI  - Neurophysiological Markers of Emotion Processing in Burnout Syndrome.
AB  - The substantial body of research employing subjective measures indicates that
      burnout syndrome is associated with cognitive and emotional dysfunctions. The
      growing amount of neurophysiological and neuroimaging research helps in
      broadening existing knowledge of the neural mechanisms underlying core burnout
      components (emotional exhaustion and depersonalization/cynicism) that are
      inextricably associated with emotional processing. In the presented EEG study, a
      group of 93 participants (55 women; mean age = 35.8) were selected for the
      burnout group or the demographically matched control group on the basis of the
      results of the Maslach Burnout Inventory - General Survey (MBI-GS) and the Areas
      of Worklife Survey (AWS). Subjects then participated in an EEG experiment using
      two experimental procedures: a facial recognition task and viewing of passive
      pictures. The study focuses on analyzing event-related potentials (ERPs): N170,
      VPP, EPN, and LPP, as indicators of emotional information processing. Our results
      show that burnout subjects, as compared to the control group, demonstrate
      significantly weaker response to affect-evoking stimuli, indexed by a decline in
      VPP amplitude to emotional faces and decreased EPN amplitude in processing
      emotional scenes. The analysis of N170 and LPP showed no significant between
      group difference. The correlation analyses revealed that VPP and EPN, which are
      ERP components related to emotional processing, are associated with two core
      burnout symptoms: emotional exhaustion and cynicism. To our knowledge, we are one
      of the first research groups to use ERPs to demonstrate such a relationship
      between neurophysiological activity and burnout syndrome in the context of
      emotional processing. Thus, in conclusion we emphasized that the decreased
      amplitude of VPP and EPN components in the burnout group may be a
      neurophysiological manifestation of emotional blunting and may be considered as
      neurophysiological markers of emotional exhaustion and cynicism. Additionally, we
      did not observe a decrease in LPP, which may be considered as a marker that
      significantly differentiates burnout from depression.

PMID- 29326620
TI  - Perseverative Thinking Questionnaire (PTQ): French Validation of a
      Transdiagnostic Measure of Repetitive Negative Thinking.
AB  - Repetitive negative thinking (RNT) is a transdiagnostic process involved in the
      onset and maintenance of many psychological disorders. The Perseverative Thinking
      Questionnaire (Ehring et al., 2011) is a content-independent scale composed of 15
      items that assesses RNT from a transdiagnostic perspective in both clinical and
      general populations. The aim of the current research was to translate and
      validate the French version of the PTQ through two studies (total N = 1016)
      following the steps for the trans-cultural validation of psychometric instruments
      (Hambleton et al., 2006). An exploratory factor analysis conducted on a first
      community sample revealed a latent structure composed of 10 items distributed on
      one common factor, labeled RNT, and three subfactors that evaluated the
      repetitive characteristic of RNT, the intrusiveness of RNT and the effect of RNT
      on mental resources. This factorial structure was confirmed in two confirmatory
      factor analyses in community and clinical samples. Scale score reliability
      indices were good and confirmed the validity of the instrument. The French
      version of the PTQ is a good content-independent instrument to assess RNT in
      general and clinical populations of French speakers.

PMID- 29326621
TI  - Editorial: What Next - The Cognition of Sequences.

PMID- 29326622
TI  - Parental Autonomy Granting and School Functioning among Chinese Adolescents: The
      Moderating Role of Adolescents' Cultural Values.
AB  - School adjustment and achievement are important indicators of adolescents' well
      being; however, few studies have examined the risk and protective factors
      predicting students' school adjustment and achievement at the individual,
      familial, and cultural level. The present study examined the influences of
      individual and familial factors and cultural values on Chinese adolescents'
      school functioning (e.g., school adjustment and grades). It also tested whether
      cultural values moderated the relationship between parenting and adolescents'
      school functioning. Self-report data were collected from a stratified random
      sample of 2,864 adolescents (51.5% female, mean age = 15.52 years, grade 6th -
      12th) from 55 classrooms, in 13 schools in Shanghai, China. Results showed that
      self-esteem (bse->adj = 0.05, SE = 0.01, p < 0.001; bse->grades = 0.08, SE =
      0.02, p < 0.001), parent-adolescent conflict (bconflict->adj = -0.03, SE = 0.00,
      p < 0.001; bconflict->grades = -0.04, SE = 0.01, p < 0.001), and conformity to
      parental expectations (bconform->adj = -0.03, SE = 0.02, p < 0.05; bconform
      >grades = 0.10, SE = 0.04, p < 0.05) all had significant effects on both school
      adjustment and grades, respectively. More importantly, results showed that
      independent self-construal moderated the relationship between parental autonomy
      granting and adolescents' grades (bindepxautom = 0.06, SE = 0.02, p < 0.01). The
      findings suggest that cultural values may influence adolescents' appraisal of
      parental autonomy granting, which then impacts their school functioning.

PMID- 29326623
TI  - Microsatellite Polymorphisms Adjacent to the Oxytocin Receptor Gene in Domestic
      Cats: Association with Personality?
AB  - A growing number of studies have explored the oxytocin system in humans and non
      human animals, and some have found important genetic polymorphisms in the
      oxytocin receptor gene (OXTR) associated with the bonding system, social
      behaviors, and personality in several species. Although single nucleotide
      polymorphisms in OXTR have been well-examined in various species, microsatellites
      (or short tandem repeats) adjacent to OXTR have rarely been studied, despite some
      suggestions that microsatellite polymorphisms near genes might play a role in
      genetic transcription and translation. In this study, we surveyed microsatellites
      in the upstream, intron, and downstream regions of OXTR in domestic cats (Felis
      catus). We succeeded in amplifying 5 out of 10 regions, and recognized these five
      regions as polymorphic. We compared allele frequencies in these five regions
      between mongrel cats in Japan (n = 100) and cats of 10 pure breeds (n = 40).
      There were significant differences in allele frequencies between the two
      populations in all microsatellite regions. Additionally, the owners of mongrel
      cats answered a comprehensive personality questionnaire, and factor analysis
      extracted four factors (Openness, Friendliness, Roughness, and Neuroticism). We
      examined the association between the microsatellite genotypes, age, sex,
      neutering status, and personality scores. Compared to their counterparts, younger
      cats tended to score higher on Openness, male cats scored higher on Friendliness,
      and female and neutered cats scored higher on Roughness. When we divided the
      sample into three groups depending on the length of alleles, we found a
      marginally significant association between Friendliness and MS3. Additionally, we
      found a sex-mediated effect of genotypes in MS4 on Friendliness, resulting in
      different effects on females and males. Our findings that mongrel cats had longer
      alleles in MS3 and MS4 than purebred cats, and that those cats tended to score
      higher on Friendliness, supported the previous findings. However, future studies
      such as comparison between purebred cats with apparently different origin or
      personality are required to determine the association of genetic variants in the
      OXTR with personality.

PMID- 29326624
TI  - Visual Search for Wines with a Triangle on the Label in a Virtual Store.
AB  - Two experiments were conducted in a virtual reality (VR) environment in order to
      investigate participants' in-store visual search for bottles of wines displaying
      a prominent triangular shape on their label. The experimental task involved
      virtually moving along a wine aisle in a virtual supermarket while searching for
      the wine bottle on the shelf that had a different triangle on its label from the
      other bottles. The results of Experiment 1 revealed that the participants
      identified the bottle with a downward-pointing triangle on its label more rapidly
      than when looking for an upward-pointing triangle on the label instead. This
      finding replicates the downward-pointing triangle superiority (DPTS) effect,
      though the magnitude of this effect was more pronounced in the first as compared
      to the second half of the experiment, suggesting a modulating role of practice.
      The results of Experiment 2 revealed that the DPTS effect was also modulated by
      the location of the target on the shelf. Interestingly, however, the results of a
      follow-up survey demonstrate that the orientation of the triangle did not
      influence the participants' evaluation of the wine bottles. Taken together, these
      findings reveal how in-store the attention of consumers might be influenced by
      the design elements in product packaging. These results therefore suggest that
      shopping in a virtual supermarket might offer a practical means of assessing the
      shelf standout of product packaging, which has important implications for food
      marketing.

PMID- 29326625
TI  - Physical Fitness Levels Do Not Affect Stress Levels in a Sample of Norwegian
      Adolescents.
AB  - Physical inactivity, low physical fitness, and perceived stress during
      adolescence are presumed to be risk factors for various disorders and subjective
      health complaints. On the other hand, physical activity and physical fitness, as
      well as mindfulness qualities, are regarded as prerequisites for health and well
      being in children and adolescent, possibly by moderating the negative effects of
      stress and protecting against stress-related health complaints. Previous studies
      have suggested gender differences in the relationship between physical
      activity/physical fitness and psychological variables. The main objective in this
      study was to evaluate how physical fitness, along with mindfulness qualities
      (MAAS-A), pain, and BMI, relate to stress (PSQ) in adolescents. Secondary
      objectives were to explore the relationship between physical fitness, mindfulness
      (MAAS-A), and BMI more explicitly in the study sample, as well as to evaluate
      possible gender differences. The cross-sectional sample included 102 Norwegian
      pupils in 10th grade (15 or 16 years). Study measurements were four items from
      the Test of Physical Fitness (TPF), the Norwegian version of the four-factor
      Perceived Stress Questionnaire (PSQ), the Norwegian version of the Mindful
      Attention Awareness Scale-Adolescent (MAAS-A), and BMI (recorded in terms of self
      reported height and weight). Additionally, pain was measured in terms of
      localization, number of pain sites, duration, and intensity (Visual analogue
      scale; VAS). According to the regression analyses, physical fitness could not
      explain any variation in stress among the adolescents. Nevertheless, there were
      some negative associations between one stress factor (lack of joy) and components
      of physical fitness at a group level, possibly influenced by conditions not
      measured in this study. As opposed to physical fitness, mindfulness qualities,
      and to some degree gender, seemed to explain variation in stress among the
      adolescents. None of the physical fitness components were associated to
      mindfulness (MAAS-A), but some components seemed negatively related to BMI,
      particularly among the males. Among the females, higher physical fitness (in
      terms of endurance) seemed related to reduced number of pain sites. Of note, the
      cross-sectional design did not allow us to determine any causal direction among
      the variables.

PMID- 29326626
TI  - Relations between Automatically Extracted Motion Features and the Quality of
      Mother-Infant Interactions at 4 and 13 Months.
AB  - Bodily movements are an essential component of social interactions. However, the
      role of movement in early mother-infant interaction has received little attention
      in the research literature. The aim of the present study was to investigate the
      relationship between automatically extracted motion features and interaction
      quality in mother-infant interactions at 4 and 13 months. The sample consisted of
      19 mother-infant dyads at 4 months and 33 mother-infant dyads at 13 months. The
      coding system Coding Interactive Behavior (CIB) was used for rating the quality
      of the interactions. Kinetic energy of upper-body, arms and head motion was
      calculated and used as segmentation in order to extract coarse- and fine-grained
      motion features. Spearman correlations were conducted between the composites
      derived from the CIB and the coarse- and fine-grained motion features. At both 4
      and 13 months, longer durations of maternal arm motion and infant upper-body
      motion were associated with more aversive interactions, i.e., more parent-led
      interactions and more infant negativity. Further, at 4 months, the amount of
      motion silence was related to more adaptive interactions, i.e., more sensitive
      and child-led interactions. Analyses of the fine-grained motion features showed
      that if the mother coordinates her head movements with her infant's head
      movements, the interaction is rated as more adaptive in terms of less infant
      negativity and less dyadic negative states. We found more and stronger
      correlations between the motion features and the interaction qualities at 4
      compared to 13 months. These results highlight that motion features are related
      to the quality of mother-infant interactions. Factors such as infant age and
      interaction set-up are likely to modify the meaning and importance of different
      motion features.

PMID- 29326627
TI  - Transfer of Training from Virtual to Real Baseball Batting.
AB  - The use of virtual environments (VE) for training perceptual-motors skills in
      sports continues to be a rapidly growing area. However, there is a dearth of
      research that has examined whether training in sports simulation transfers to the
      real task. In this study, the transfer of perceptual-motor skills trained in an
      adaptive baseball batting VE to real baseball performance was investigated.
      Eighty participants were assigned equally to groups undertaking adaptive hitting
      training in the VE, extra sessions of batting practice in the VE, extra sessions
      of real batting practice, and a control condition involving no additional
      training to the players' regular practice. Training involved two 45 min sessions
      per week for 6 weeks. Performance on a batting test in the VE, in an on-field
      test of batting, and on a pitch recognition test was measured pre- and post
      training. League batting statistics in the season following training and the
      highest level of competition reached in the following 5 years were also analyzed.
      For the majority of performance measures, the adaptive VE training group showed a
      significantly greater improvement from pre-post training as compared to the other
      groups. In addition, players in this group had superior batting statistics in
      league play and reached higher levels of competition. Training in a VE can be
      used to improve real, on-field performance especially when designers take
      advantage of simulation to provide training methods (e.g., adaptive training)
      that do not simply recreate the real training situation.

PMID- 29326628
TI  - Recreational Diving Practice for Stress Management: An Exploratory Trial.
AB  - Background: Within the components of Scuba diving there are similarities with
      meditation and mindfulness techniques by training divers to be in a state of open
      monitoring associated with slow and ample breathing. Perceived stress is known to
      be diminished during meditation practice. This study evaluates the benefits of
      scuba diving on perceived stress and mindful functioning. Method: A recreational
      diving group (RDG; n = 37) was compared with a multisport control group (MCG; n =
      30) on perceived stress, mood, well-being and mindfulness by answering auto
      questionnaires before and after a 1-week long UCPA course. For the diving group,
      stability of the effects was evaluated 1 month later using similar auto
      questionnaires. Results: Perceived stress did not decrease after the course for
      the MCG [ The divers showed a significant reduction on the perceived stress score
      (p < 0.05) with a sustainable effect (p = 0.01)]. An improvement in mood scale
      was observed in both groups. This was associated to an increase in mindfulness
      abilities. Conclusions: The practice of a recreational sport improves the mood of
      subjects reporting the thymic benefits of a physical activity performed during a
      vacation period. The health benefits of recreational diving appear to be greater
      than the practice of other sports in reducing stress and improving well-being.

PMID- 29326629
TI  - Parental Emotion Socialization and Child Psychological Adjustment among Chinese
      Urban Families: Mediation through Child Emotion Regulation and Moderation through
      Dyadic Collaboration.
AB  - The theoretical model of emotion regulation and many empirical findings have
      suggested that children's emotion regulation may mediate the association between
      parents' emotion socialization and children's psychological adjustment. However,
      limited research has been conducted on moderators of these relations, despite the
      argument that the associations between parenting practices and children's
      psychological adjustment are probabilistic rather than deterministic. This study
      examined the mediating role of children's emotion regulation in linking parents'
      emotion socialization and children's psychological adjustment, and whether dyadic
      collaboration could moderate the proposed mediation model in a sample of Chinese
      parents and their children in their middle childhood. Participants were 150
      Chinese children (87 boys and 63 girls, Mage = 8.54, SD = 1.67) and their parents
      (Mage = 39.22, SD = 4.07). Parent-child dyadic collaboration was videotaped and
      coded from an interaction task. Parents reported on their emotion socialization,
      children's emotion regulation and psychopathological symptoms. Results indicated
      that child emotion regulation mediated the links between parental emotion
      socialization and child's psychopathological symptoms. Evidence of moderated
      mediation was also found: supportive emotion socialization and child emotion
      regulation were positively correlated only at high and medium levels of dyadic
      collaboration, with child's psychopathological symptoms as the dependent
      variables. Our findings suggested that higher-level parent-child collaboration
      might further potentiate the protective effect of parental supportive emotion
      socialization practices against child psychopathological symptoms.

PMID- 29326630
TI  - Underlying Processes of an Inverted Personalization Effect in Multimedia Learning
      - An Eye-Tracking Study.
AB  - One of the frequently examined design principles in multimedia learning is the
      personalization principle. Based on empirical evidence this principle states that
      using personalized messages in multimedia learning is more beneficial than using
      formal language (e.g., using 'you' instead of 'the'). Although there is evidence
      that these slight changes in regard to the language style affect learning,
      motivation and the perceived cognitive load, it remains unclear, (1) whether the
      positive effects of personalized language can be transferred to all kinds of
      content of learning materials (e.g., specific potentially aversive health issues)
      and (2) which are the underlying processes (e.g., attention allocation) of the
      personalization effect. German university students (N = 37) learned symptoms and
      causes of cerebral hemorrhages either with a formal or a personalized version of
      the learning material. Analysis revealed comparable results to the few existing
      previous studies, indicating an inverted personalization effect for potentially
      aversive learning material. This effect was specifically revealed in regard to
      decreased average fixation duration and the number of fixations exclusively on
      the images in the personalized compared to the formal version. These results can
      be seen as indicators for an inverted effect of personalization on the level of
      visual attention.

PMID- 29326631
TI  - Cyclists' Anger As Determinant of Near Misses Involving Different Road Users.
AB  - Road anger constitutes one of the determinant factors related to safety outcomes
      (e.g., accidents, near misses). Although cyclists are considered vulnerable road
      users due to their relatively high rate of fatalities in traffic, previous
      research has solely focused on car drivers, and no study has yet investigated the
      effect of anger on cyclists' safety outcomes. The present research aims to
      investigate, for the first time, the effects of cycling anger toward different
      types of road users on near misses involving such road users and near misses in
      general. Using a daily diary web-based questionnaire, we collected data about
      daily trips, bicycle use, near misses experienced, cyclist's anger and
      demographic information from 254 Spanish cyclists. Poisson regression was used to
      assess the association of cycling anger with near misses, which is a count
      variable. No relationship was found between general cycling anger and near misses
      occurrence. Anger toward specific road users had different effects on the
      probability of near misses with different road users. Anger toward the
      interaction with car drivers increased the probability of near misses involving
      cyclists and pedestrians. Anger toward interaction with pedestrians was
      associated with higher probability of near misses with pedestrians. Anger toward
      cyclists exerted no effect on the probability of near misses with any road user
      (i.e., car drivers, cyclists or pedestrians), whereas anger toward the
      interactions with the police had a diminishing effect on the occurrence of near
      misses' involving all types of road users. The present study demonstrated that
      the effect of road anger on safety outcomes among cyclists is different from that
      of motorists. Moreover, the target of anger played an important role on safety
      both for the cyclist and the specific road users. Possible explanations for these
      differences are based on the difference in status and power with motorists, as
      well as on the potential displaced aggression produced by the fear of retaliation
      by motorized vehicle users.

PMID- 29326632
TI  - Sending Nudes: Sex, Self-Rated Mate Value, and Trait Machiavellianism Predict
      Sending Unsolicited Explicit Images.
AB  - Modern dating platforms have given rise to new dating and sexual behaviors. In
      the current study, we examine predictors of sending unsolicited explicit images,
      a particularly underexplored online sexual behavior. The aim of the current study
      was to explore the utility of dark personality traits (i.e., narcissism,
      Machiavellianism, psychopathy, and sadism) and self-rated mate value in
      predicting attitudes toward and behavior of sending unsolicited explicit images.
      Two hundred and forty participants (72% female; Mage = 25.96, SD = 9.79)
      completed an online questionnaire which included a measure of self-rated mate
      value, a measure of dark personality traits, and questions regarding sending
      unsolicited explicit images (operationalized as the explicit image scale). Men,
      compared to women, were found to have higher explicit image scale scores, and
      both self-rated mate value and trait Machiavellianism were positive predictors of
      explicit image scale scores. Interestingly, there were no significant
      interactions between sex and these variables. Further, Machiavellianism mediated
      all relationships between other dark traits and explicit image scale scores,
      indicating this behavior is best explained by the personality trait associated
      with behavioral strategies. In sum, these results provide support for the premise
      that sending unsolicited explicit images may be a tactic of a short-term mating
      strategy; however, future research should further explore this claim.

PMID- 29326633
TI  - Editorial: Psychosocial Job Dimensions and Distress/Well-Being: Issues and
      Challenges in Occupational Health Psychology.

PMID- 29326634
TI  - When Sugar-Coated Words Taste Dry: The Relationship between Gender, Anxiety, and
      Response to Irony.
AB  - This article approaches the question of mocking compliments and ironic praise
      from an interactional gender perspective. A statement such as "You're a real
      genius!" could easily be interpreted as a literal compliment, as playful humor or
      as an offensive insult. We investigate this thin line in the use of irony among
      adult men and women. The research introduces an interactional approach to irony,
      through the lens of gender stereotype bias. The main question concerns the impact
      of individual differences and gender effect on the perception and production of
      ironic comments. Irony Processing Task (IPT), developed by Milanowicz (2016), was
      applied in order to study the production and perception of ironic criticism and
      ironic praise in adult males and females. It is a rare case of a study measuring
      the ability to create irony because, unlike most of known irony research, it is
      not a multiple choice test where participants are given the response options. The
      IPT was also used to assess the asymmetry of affect (humor vs. malice) and impact
      of gender effect in the perception of ironic comments. Results are analyzed in
      relation to the State-Trait Anxiety Inventory (STAI) scores. The findings reveal
      the interactional relationship between gender and response to irony. Male
      responses were consistently more ironic than female's, across all experimental
      conditions, and female responses varied more. Both, men and women used more irony
      in response to male ironic criticism but female ironic praise. Anxiety proved to
      be a moderate predictor of irony comprehension and willingness to use irony.
      Data, collected in control and two gender stereotype activation conditions, also
      corroborates the assumption that the detection of compliments and the detection
      of criticism can be moderated by the attitude activation effect. The results are
      interpreted within the framework of linguistic intergroup bias (LIB) and natural
      selection strategies.

PMID- 29326637
TI  - When More Is Better - Consumption Priming Decreases Responders' Rejections in the
      Ultimatum Game.
AB  - During the past decades, economic theories of rational choice have been exposed
      to outcomes that were severe challenges to their claim of universal validity. For
      example, traditional theories cannot account for refusals to cooperate if
      cooperation would result in higher payoffs. A prominent illustration are
      responders' rejections of positive but unequal payoffs in the Ultimatum Game. To
      accommodate this anomaly in a rational framework one needs to assume both a
      preference for higher payoffs and a preference for equal payoffs. The current set
      of studies shows that the relative weight of these preference components depends
      on external conditions and that consumption priming may decrease responders'
      rejections of unequal payoffs. Specifically, we demonstrate that increasing the
      accessibility of consumption-related information accentuates the preference for
      higher payoffs. Furthermore, consumption priming increased responders' reaction
      times for unequal payoffs which suggests an increased conflict between both
      preference components. While these results may also be integrated into existing
      social preference models, we try to identify some basic psychological processes
      underlying economic decision making. Going beyond the Ultimatum Game, we propose
      that a distinction between comparative and deductive evaluations may provide a
      more general framework to account for various anomalies in behavioral economics.

PMID- 29326635
TI  - Beyond Disease: Happiness, Goals, and Meanings among Persons with Multiple
      Sclerosis and Their Caregivers.
AB  - The experience of persons with multiple sclerosis (MS) and their caregivers is
      usually investigated in terms of emotional distress and health-related quality of
      life, while well-being indicators remain largely underexplored. In addition,
      findings are often interpreted from the clinical perspective, neglecting socio
      cultural aspects that may crucially contribute to individuals' functioning. At
      the methodological level, most studies rely on scaled instruments, not allowing
      participants to freely express their needs and resources. Based on the bio-psycho
      social perspective endorsed by the International Classification of Functioning,
      well-being indicators were investigated among 62 persons with MS (PwMS), their 62
      caregivers and two control groups, matched by age and gender. Participants
      completed the Positive Affect Negative Affect Schedule (PANAS), the Satisfaction
      with Life Scale (SWLS), and the Eudaimonic and Hedonic Happiness Investigation
      instrument (EHHI). EHHI provides information on participants' happiness, goals
      and meanings through scaled and open-ended questions, contextualized within major
      life domains. No relevant differences emerged among PwMS and caregivers, compared
      with the respective control groups, as concerns life domains associated with
      happiness, goals and meaning. Participants across groups prominently mentioned
      family, highlighting its intrinsic value and its relevance as a sharing context;
      health did not represent a major theme for PwMS; community, society and
      religion/spirituality issues were substantially neglected by all participants.
      PwMS and caregivers reported lower levels of positive affect than their control
      groups, while no substantial differences emerged for negative affect, happiness
      and meaningfulness levels in life and across most domains. Results suggest that
      the experience of MS is associated with well-being in relevant life domains, such
      as family and close relationships. Although PwMS and caregivers identified a
      lower number of goals and meaning-related opportunities compared to control
      groups, they showed a positive adjustment to disease through the development of
      personal and family resources. These assets are often undervalued by health
      professionals and social institutions, while they could be fruitfully exploited
      through the active involvement of PwMS and their families as expert and exemplary
      informants in initiatives aimed at promoting the well-being of individuals and
      communities.

PMID- 29326638
TI  - Spatial Release from Masking with a Moving Target.
AB  - In the visual domain, a stationary object that is difficult to detect usually
      becomes far more salient if it moves while the objects around it do not. This
      "pop out" effect is important for parsing the visual world into figure/ground
      relationships that allow creatures to detect food, threats, etc. We tested for an
      auditory correlate to this visual effect by asking listeners to identify a single
      word, spoken by a female, embedded with two or four masking words spoken by
      males. Percentage correct scores were analyzed and compared between conditions
      where target and maskers were presented from the same position vs. when the
      target was presented from one position while maskers were presented from
      different positions. In some trials, the target word was moved across the speaker
      array using amplitude panning, while in other trials that target was played from
      a single, static position. Results showed a spatial release from masking for all
      conditions where the target and maskers were not located at the same position,
      but there was no statistically significant difference between identification
      performance when the target was moving vs. when it was stationary. These results
      suggest that, at least for short stimulus durations (0.75 s for the stimuli in
      this experiment), there is unlikely to be a "pop out" effect for moving target
      stimuli in the auditory domain as there is in the visual domain.

PMID- 29326636
TI  - Uncovering the Mechanisms Responsible for Why Language Learning May Promote
      Healthy Cognitive Aging.
AB  - One of the great challenges facing humankind in the 21st century is preserving
      healthy brain function in our aging population. Individuals over 60 are the
      fastest growing age group in the world, and by 2050, it is estimated that the
      number of people over the age of 60 will triple. The typical aging process
      involves cognitive decline related to brain atrophy, especially in frontal brain
      areas and regions that subserve declarative memory, loss of synaptic connections,
      and the emergence of neuropathological symptoms associated with dementia. The
      disease-state of this age-related cognitive decline is Alzheimer's disease and
      other dementias, which may cause older adults to lose their independence and rely
      on others to live safely, burdening family members and health care systems in the
      process. However, there are two lines of research that offer hope to those
      seeking to promote healthy cognitive aging. First, it has been observed that
      lifestyle variables such as cognitive leisure activities can moderate the risk of
      Alzheimer's disease, which has led to the development of plasticity-based
      interventions for older adults designed to protect against the adverse effects of
      cognitive decline. Second, there is evidence that lifelong bilingualism acts as a
      safeguard in preserving healthy brain function, possibly delaying the incidence
      of dementia by several years. In previous work, we have suggested that foreign
      language learning programs aimed at older populations are an optimal solution for
      building cognitive reserve because language learning engages an extensive brain
      network that is known to overlap with the regions negatively affected by the
      aging process. Here, we will outline potential future lines of research that may
      uncover the mechanism responsible for the emergence of language learning related
      brain advantages, such as language typology, bi- vs. multi-lingualism, age of
      acquisition, and the elements that are likely to result in the largest gains.

PMID- 29326639
TI  - The Effects of Animacy and Syntax on Priming: A Developmental Study.
AB  - Sentence production relies on the activation of semantic information (e.g., noun
      animacy) and syntactic frames that specify an order for grammatical functions
      (e.g., subject before object). However, it is unclear whether these semantic and
      syntactic processes interact and if this might change over development. We thus
      examined the extent to which animacy-semantic role mappings in dative prime
      sentences and target scenes influences choice of syntactic structure (structural
      priming, analysis 1) and ordering of nouns as a function of animacy (animacy noun
      priming, analysis 2) in children and adults. One hundred forty-three participants
      (47 three year olds, 48 five year olds and 48 adults) alternated with the
      experimenter in describing animations. Animacy mappings for themes and goals were
      either prototypical or non-prototypical and either matched or mismatched across
      the experimenter's prime scenes and participants' target elicitation scenes.
      Prime sentences were either double-object datives (DOD e.g., the girl brought the
      monkey a ball) or prepositional datives (PD e.g., the girl brought the ball to
      the monkey), and occurred with either animate-inanimate or inanimate-animate,
      post-verbal noun order. Participants' target sentences were coded for syntactic
      form, and animacy noun order. All age groups showed a structural priming effect.
      A significant interaction between prime structure, prime animacy-semantic role
      mappings and prime-target match indicated that animacy could moderate structural
      priming in 3 year olds. However, animacy had no effect on structural priming in
      any other instance. Nevertheless, production of DOD structures was influenced by
      whether animacy-semantic role mappings in primes and target scenes matched or
      mismatched. We provide new evidence of animacy noun order priming effects in 3
      and 5 year olds where there was prime-target match in animacy-semantic role
      mappings. Neither prime animacy noun ordering nor animacy-semantic role mappings
      influenced adults' target sentences. Our results demonstrate that animacy cues
      can affect speakers' word order independently of syntactic structure and also
      through interactions with syntax, although these processes are subject to
      developmental changes. We therefore, suggest that theories of structural priming,
      sentence production, linguistic representation and language acquisition all need
      to explicitly account for developmental changes in the role of semantic and
      syntactic information in sentence processing.

PMID- 29326640
TI  - Analysis of Amyloid-beta Pathology Spread in Mouse Models Suggests Spread Is
      Driven by Spatial Proximity, Not Connectivity.
AB  - While the spread of some neurodegenerative disease-associated proteinopathies,
      such as tau and alpha-synuclein, is well studied and clearly implicates
      transsynaptic pathology transmission, research into the progressive spread of
      amyloid-beta pathology has been less clear. In fact, prior analyses of
      transregional amyloid-beta pathology spread have implicated both transsynaptic
      and other intracellular- as well as extracellular-based transmission mechanisms.
      We therefore conducted the current meta-analytic analysis to help assess whether
      spatiotemporal amyloid-beta pathology development patterns in mouse models, where
      regional proteinopathy is more directly characterizable than in patients, better
      fit with transsynaptic- or extracellular-based theories of pathology spread. We
      find that, consistently across the datasets used in this study, spatiotemporal
      amyloid-beta pathology patterns are more consistent with extracellular-based
      explanations of pathology spread. Furthermore, we find that regional levels of
      amyloid precursor protein in a mouse model are also better correlated with
      expected pathology patterns based on extracellular, rather than intracellular or
      transsynaptic spread.

PMID- 29326642
TI  - Spinal Cavernomas: Outcome of Surgically Treated 10 Patients.
AB  - Aim: We report the preoperative and postoperative findings and also neurological
      follow-up results from 10 spinal cavernoma patients treated in our clinic.
      Several representative cases are presented in terms of clinical features, imaging
      results, and surgical outcomes. Material and methods: The data were
      retrospectively collected from patients' files in the hospital records and sorted
      with regards to clinical presentation, radiologic features, and operative
      findings. Patients received spinal MRI scans for the diagnosis of spinal
      cavernomas (SC) and postsurgical evaluation. Clinical presentation was evaluated
      via Ogilvy classification and symptoms were checked preoperatively and
      postoperatively at third month and first year using McCormick scale. Primary
      treatment was microsurgical operation aiming a gross total lesion resection.
      Results: 10 spinal cavernoma patients between the ages 30 and 63 were treated.
      Six (60%) of the patients were diagnosed with cervical and four (40%) others were
      diagnosed with thoracic SC. Among the patient group, mean preoperative Ogilvy
      classification score was 2.3 +/- 0.7.8 and McCormick score was 1.9 +/- 0.7. There
      was no residual mass or relapse after surgery. One patient developed surgery
      related left hemiparesis, which was normalized at 1 year follow-up. Conclusion:
      Patients must be diagnosed with MRI since it is nowadays a gold standard.
      Preoperative and postoperative scores are important in evaluating the patients'
      condition and improvement. The results from our patient series also reinforce the
      notion that immediate surgery should be the preferred treatment method for
      cavernomas. Intraoperative neurophysiologic monitarization should assist the
      surgery in order to prevent complications. In conclusion, microsurgery is a gold
      standard method that we recommend for cases of cavernomas, which will not recur
      if gross total resection is achieved.

PMID- 29326641
TI  - The TGF-beta System As a Potential Pathogenic Player in Disease Modulation of
      Amyotrophic Lateral Sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) represents a fatal orphan disease with high
      unmet medical need, and a life time risk of approx. 1/400 persons per population.
      Based on increasing knowledge on pathophysiology including genetic and molecular
      changes, epigenetics, and immune dysfunction, inflammatory as well as fibrotic
      processes may contribute to the heterogeneity and dynamics of ALS. Animal and
      human studies indicate dysregulations of the TGF-beta system as a common feature
      of neurodegenerative disorders in general and ALS in particular. The TGF-beta
      system is involved in different essential developmental and physiological
      processes and regulates immunity and fibrosis, both affecting neurogenesis and
      neurodegeneration. Therefore, it has emerged as a potential therapeutic target
      for ALS: a persistent altered TGF-beta system might promote disease progression
      by inducing an imbalance of neurogenesis and neurodegeneration. The current study
      assessed the activation state of the TGF-beta system within the periphery/in life
      disease stage (serum samples) and a late stage of disease (central nervous system
      tissue samples), and a potential influence upon neuronal stem cell (NSC)
      activity, immune activation, and fibrosis. An upregulated TGF-beta system was
      suggested with significantly increased TGF-beta1 protein serum levels, enhanced
      TGF-beta2 mRNA and protein levels, and a strong trend toward an increased TGF
      beta1 protein expression within the spinal cord (SC). Stem cell activity appeared
      diminished, reflected by reduced mRNA expression of NSC markers Musashi-1 and
      Nestin within SC-paralleled by enhanced protein contents of Musashi-1.
      Doublecortin mRNA and protein expression was reduced, suggesting an arrested
      neurogenesis at late stage ALS. Chemokine/cytokine analyses suggest a shift from
      a neuroprotective toward a more neurotoxic immune response: anti-inflammatory
      chemokines/cytokines were unchanged or reduced, expression of proinflammatory
      chemokines/cytokines were enhanced in ALS sera and SC postmortem tissue. Finally,
      we observed upregulated mRNA and protein expression for fibronectin in motor
      cortex of ALS patients which might suggest increased fibrotic changes. These data
      suggest that there is an upregulated TGF-beta system in specific tissues in ALS
      that might lead to a "neurotoxic" immune response, promoting disease progression
      and neurodegeneration. The TGF-beta system therefore may represent a promising
      target in treatment of ALS patients.

PMID- 29326643
TI  - The Temporal Retinal Nerve Fiber Layer Thickness Is the Most Important Optical
      Coherence Tomography Estimate in Multiple Sclerosis.
AB  - Background: Reduced peripapillary retinal nerve fiber layer (pRNFL) and combined
      ganglion cell and inner plexiform layer (GCIP) thicknesses as measured by optical
      coherence tomography (OCT) have been observed in multiple sclerosis (MS)
      patients. The purpose was to determine the most associative OCT measure to level
      of cognitive and physical disability in MS. Methods: Data were collected from 546
      MS patients and 175 healthy controls (HCs). We compared the average pRNFL,
      temporal pRNFL (T-pRNFL), overall inner ganglion cell/inner plexiform layer
      (GCIP), and the overall ganglion cell complex (GCC) including macular RNFL and
      GCIP thicknesses measurements in differentiating MS subtypes from HCs. The
      association between OCT measures, Expanded Disability Status Scale (EDSS), and
      Symbol Digit Modalities Test (SDMT) were assessed using generalized estimating
      equations models. Results: Both peripapillary and macular OCT measurements could
      differentiate all MS subtypes from HCs. The SDMT score was significantly
      associated with reduced thickness of all OCT measures, mostly in average pRNFL
      (0.14 um, P = 0.001) and T-pRNFL (0.17 um, P < 0.001). The EDSS score was
      significantly associated with reduced inner retinal layer thickness. The largest
      reduction was seen in T-pRNFL (-1.52 MUm, P < 0.001) and inner GCC (-1.78 MUm, P
      < 0.001). Conclusion: The T-pRNFL is highly sensitive and associated with level
      of both cognitive and physical disability.

PMID- 29326645
TI  - Segregation of Spontaneous and Training Induced Recovery from Visual Field
      Defects in Subacute Stroke Patients.
AB  - Whether rehabilitation after stroke profits from an early start is difficult to
      establish as the contributions of spontaneous recovery and treatment are
      difficult to tease apart. Here, we use a novel training design to dissociate
      these components for visual rehabilitation of subacute stroke patients with
      visual field defects such as hemianopia. Visual discrimination training was
      started within 6 weeks after stroke in 17 patients. Spontaneous and training
      induced recoveries were distinguished by training one-half of the defect for 8
      weeks, while monitoring spontaneous recovery in the other (control) half of the
      defect. Next, trained and control regions were swapped, and training continued
      for another 8 weeks. The same paradigm was also applied to seven chronic patients
      for whom spontaneous recovery can be excluded and changes in the control half of
      the defect point to a spillover effect of training. In both groups, field
      stability was assessed during a no-intervention period. Defect reduction was
      significantly greater in the trained part of the defect than in the
      simultaneously untrained part of the defect irrespective of training onset (p =
      0.001). In subacute patients, training contributed about twice as much to their
      defect reduction as the spontaneous recovery. Goal Attainment Scores were
      significantly and positively correlated with the total defect reduction (p =
      0.01), percentage increase reading speed was significantly and positively
      correlated with the defect reduction induced by training (epoch 1: p = 0.0044;
      epoch 2: p = 0.023). Visual training adds significantly to the spontaneous
      recovery of visual field defects, both during training in the early and the
      chronic stroke phase. However, field recovery as a result of training in this
      subacute phase was as large as in the chronic phase. This suggests that patients
      benefited primarily of early onset training by gaining access to a larger visual
      field sooner.

PMID- 29326644
TI  - Remote Diffusion-Weighted Imaging Lesions in Intracerebral Hemorrhage:
      Characteristics, Mechanisms, Outcomes, and Therapeutic Implications.
AB  - Spontaneous intracerebral hemorrhage (ICH) is one of the most fatal form of
      stroke, with high mortality and disability rate. Small diffusion-weighed imaging
      lesions are not rare to see in regions remote from the hematoma after ICH and
      have been generally considered as related with poor outcome. In this review, we
      described the characteristics of remote ischemic lesions, discussed the possible
      mechanisms and clinical outcomes of these lesions, and evaluated the potential
      therapeutic implications.

PMID- 29326646
TI  - Impaired Emotional Mirroring in Parkinson's Disease-A Study on Brain Activation
      during Processing of Facial Expressions.
AB  - Background: Affective dysfunctions are common in patients with Parkinson's
      disease, but the underlying neurobiological deviations have rarely been examined.
      Parkinson's disease is characterized by a loss of dopamine neurons in the
      substantia nigra resulting in impairment of motor and non-motor basal ganglia
      cortical loops. Concerning emotional deficits, some studies provide evidence for
      altered brain processing in limbic- and lateral-orbitofrontal gating loops. In a
      second line of evidence, human premotor and inferior parietal homologs of mirror
      neuron areas were involved in processing and understanding of emotional facial
      expressions. We examined deviations in brain activation during processing of
      facial expressions in patients and related these to emotion recognition accuracy.
      Methods: 13 patients and 13 healthy controls underwent an emotion recognition
      task and a functional magnetic resonance imaging (fMRI) measurement. In the
      Emotion Hexagon test, participants were presented with blends of two emotions and
      had to indicate which emotion best described the presented picture. Blended
      pictures with three levels of difficulty were included. During fMRI scanning,
      participants observed video clips depicting emotional, non-emotional, and neutral
      facial expressions or were asked to produce these facial expressions themselves.
      Results: Patients performed slightly worse in the emotion recognition task, but
      only when judging the most ambiguous facial expressions. Both groups activated
      inferior frontal and anterior inferior parietal homologs of mirror neuron areas
      during observation and execution of the emotional facial expressions. During
      observation, responses in the pars opercularis of the right inferior frontal
      gyrus, in the bilateral inferior parietal lobule and in the bilateral
      supplementary motor cortex were decreased in patients. Furthermore, in patients,
      activation of the right anterior inferior parietal lobule was positively related
      to accuracy in the emotion recognition task. Conclusion: Our data provide
      evidence for a contribution of human homologs of monkey mirror areas to the
      emotion recognition deficit in Parkinson's disease.

PMID- 29326647
TI  - Non-24-Hour Sleep-Wake Rhythm Disorder in the Totally Blind: Diagnosis and
      Management.
AB  - Several aspects of human physiology and behavior are dominated by 24-h circadian
      rhythms with key impacts on health and well-being. These include mainly the sleep
      wake cycle, vigilance and performance patterns, and some hormone secretions. The
      rhythms are generated spontaneously by an internal "pacemaker," the
      suprachiasmatic nuclei within the anterior hypothalamus. This master clock has,
      for most humans, an intrinsic rhythm slightly longer than 24 h. Daily retinal
      light exposure is necessary for the synchronization of the circadian rhythms with
      the external 24-h solar environment. This daily synchronization process generally
      poses no problems for sighted individuals except in the context of jetlag or
      working night shifts being conditions of circadian desynchrony. However, many
      blind subjects with no light perception had periodical circadian desynchrony, in
      the absence of light information to the master clock leading to poor circadian
      rhythm synchronization. Affected patients experience cyclical or periodic
      episodes of poor sleep and daytime dysfunction, severely interfering with social,
      academic, and professional life. The diagnosis of Non-24 Sleep-Wake Rhythm
      Disorder, also named free-running disorder, non-entrained disorder, or
      hypernycthemeral syndrome, remains challenging from a clinical point of view due
      to the cyclical symptoms and should be confirmed by measurements of circadian
      biomarkers such as urinary melatonin to demonstrate a circadian period outside
      the normal range. Management includes behavioral modification and melatonin.
      Tasimelteon, a novel melatonin receptor 1 and 2 agonist, has demonstrated its
      effectiveness and safety with an evening dose of 20 mg and is currently the only
      treatment approved by the FDA and the European Medicines Agency.

PMID- 29326648
TI  - Functional MRI Motor Imagery Tasks to Detect Command Following in Traumatic
      Disorders of Consciousness.
AB  - Severe traumatic brain injury impairs arousal and awareness, the two components
      of consciousness. Accurate diagnosis of a patient's level of consciousness is
      critical for determining treatment goals, access to rehabilitative services, and
      prognosis. The bedside behavioral examination, the current clinical standard for
      diagnosis of disorders of consciousness, is prone to misdiagnosis, a finding that
      has led to the development of advanced neuroimaging techniques aimed at detection
      of conscious awareness. Although a variety of paradigms have been used in
      functional magnetic resonance imaging (fMRI) to reveal covert consciousness, the
      relative accuracy of these paradigms in the patient population is unknown. Here,
      we compare the rate of covert consciousness detection by hand squeezing and
      tennis playing motor imagery paradigms in 10 patients with traumatic disorders of
      consciousness [six male, six acute, mean +/- SD age = 27.9 +/- 9.1 years, one
      coma, four unresponsive wakefulness syndrome, two minimally conscious without
      language function, and three minimally conscious with language function, per
      bedside examination with the Coma Recovery Scale-Revised (CRS-R)]. We also tested
      the same paradigms in 10 healthy subjects (nine male, mean +/- SD age = 28.5 +/-
      9.4 years). In healthy subjects, the hand squeezing paradigm detected covert
      command following in 7/10 and the tennis playing paradigm in 9/10 subjects. In
      patients who followed commands on the CRS-R, the hand squeezing paradigm detected
      covert command following in 2/3 and the tennis playing paradigm in 0/3 subjects.
      In patients who did not follow commands on the CRS-R, the hand squeezing paradigm
      detected command following in 1/7 and the tennis playing paradigm in 2/7
      subjects. The sensitivity, specificity, and accuracy (ACC) of detecting covert
      command following in patients who demonstrated this behavior on the CRS-R was
      66.7, 85.7, and 80% for the hand squeezing paradigm and 0, 71.4, and 50% for the
      tennis playing paradigm, respectively. Overall, the tennis paradigm performed
      better than the hand squeezing paradigm in healthy subjects, but in patients, the
      hand squeezing paradigm detected command following with greater ACC. These
      findings indicate that current fMRI motor imagery paradigms frequently fail to
      detect command following and highlight the need for paradigm optimization to
      improve the accuracy of covert consciousness detection.

PMID- 29326649
TI  - Neck Vibration Proprioceptive Postural Response Intact in Progressive
      Supranuclear Palsy unlike Idiopathic Parkinson's Disease.
AB  - Progressive supranuclear palsy (PSP) and late-stage idiopathic Parkinson's
      disease (IPD) are neurodegenerative movement disorders resulting in different
      postural instability and falling symptoms. IPD falls occur usually forward in
      late stage, whereas PSP falls happen in early stages, mostly backward,
      unprovoked, and with high morbidity. Postural responses to sensory
      anteroposterior tilt illusion by bilateral dorsal neck vibration were probed in
      both groups versus healthy controls on a static recording posture platform. Three
      distinct anteroposterior body mass excursion peaks (P1-P3) were observed. 18 IPD
      subjects exhibited well-known excessive response amplitudes, whereas 21 PSP
      subjects' responses remained unaltered to 22 control subjects. Neither IPD nor
      PSP showed response latency deficits, despite brainstem degeneration especially
      in PSP. The observed response patterns suggest that PSP brainstem pathology might
      spare the involved proprioceptive pathways and implies viability of neck
      vibration for possible biofeedback and augmentation therapy in PSP postural
      instability.

PMID- 29326650
TI  - The Patterns of Recurrences in Idiopathic Benign Paroxysmal Positional Vertigo
      and Self-treatment Evaluation.
AB  - Background and Objectives: Benign paroxysmal positional vertigo (BPPV) recurs
      frequently. This study aims to determine that each patient with BPPV has a
      predilection for a specific canal and the type of recurred BPPV can be predicted
      from that observed during the previous attack. Methods: The involved side (right,
      left, and bilateral) and affected canal (posterior, geotropic horizontal,
      apogeotropic horizontal, anterior, and mixed) were analyzed in 224 pairs of
      consecutive attacks of BPPV confirmed in 167 patients at the Dizziness Clinic of
      Seoul National Bundang Hospital from 2003 to 2017. We defined the recurrence when
      patients had the redevelopment of BPPV at least 1 week after resolution of the
      previous one. Results: During the initial attack, the involved canals were
      posterior in 134 (59.8%), geotropic horizontal in 53 (23.7%), apogeotropic
      horizontal in 27 (12.1%), anterior in 5 (2.2%), and mixed in 5 (2.2%). The right
      ear was more commonly affected than the left ear [132 (58.9%) vs. 90 (40.2%)].
      Two patients (0.9%) showed bilateral involvements. During the recurrences, the
      proportions of involved canals and affected side were similar irrespective of
      those during the former event. Only 24% of the patients showed the recurrence in
      the same canal on the same side. Conclusion: The patterns of recurrences are
      usually discordant in patients with BPPV. Instruction for self-administration of
      a specific canalith repositioning procedure based on the previous type of BPPV
      may have a limited efficacy in this frequently recurrent disorder.

PMID- 29326652
TI  - Clinical Epidemiology of Head Injury from Road-Traffic Trauma in a Developing
      Country in the Current Era.
AB  - Objectives: Africa and other Asian low middle-income countries account for the
      greatest burden of the global road-traffic injury (RTI)-related head injury (HI).
      This study set out to describe the incidence, causation, and severity of RTI
      related HI and associated injuries in a Nigerian academic neurosurgical practice.
      Methods: This is a retrospective cross-sectional analysis of RTI-related HI from
      a prospective HI registry in an academic neurosurgery practice in Nigeria.
      Results: All-terrain RTI accounted for 80.6% (833/1,034) of HI over a 7-year
      study period. All age groups were involved, mean 33.06 years (SD 18.30), mode 21
      30, 231/833 (27.7%). The male:female ratio was 631:202, ~3:1. The road trauma
      occurred exclusively from motorcycle-and motor-vehicle crash (MCC/MVC), MCC
      caused 56.8% (473/833) of these; the victims were vulnerable road users (VRU) in
      74%, and >90% belong in the low socioeconomic class. Using the Glasgow Coma Scale
      grading, the HI was moderate/severe in 52%; loss of consciousness occurred in
      93%, the Abbreviated Injury Severity-head > 3 in 74%, and computed tomography
      (CT) Rotterdam score > 3 in 52%. Significant extracranial injuries occurred in
      many organ systems, 421/833 (50.5%) having Injury Severity Score (ISS) > 25.
      Surgical lesions included extensive brain contusions in 157 (18.8%); acute
      extradural hematoma in 34 (4.1%); acute subdural hematoma in 32 (3.8%); and
      traumatic intracerebral hemorrhage in 27 (3.2%), but only 97 (11.6%) received
      operative care for various logistic reasons. The in-hospital outcome was good in
      71.3% and poor in 28.7%; the statistically significant (p < 0.001) determinants
      of this outcome profile were the severity of the HI, the CT Rotterdam score, and
      the ISS. Conclusion: In this study from Nigeria, RTI-related HI emanates from
      significant trauma to vulnerable road users and are caused exclusively by
      motorcycles and motor vehicles.

PMID- 29326651
TI  - Comparison of 3- and 20-Gradient Direction Diffusion-Weighted Imaging in a
      Clinical Subacute Cohort of Patients with Transient Ischemic Attack: Application
      of Standard Vendor Protocols for Lesion Detection and Final Infarct Size
      Projection.
AB  - Objective: Diffusion tensor imaging may aid brain ischemia assessment but is more
      time consuming than conventional diffusion-weighted imaging (DWI). We compared 3
      gradient direction DWI (3DWI) and 20-gradient direction DWI (20DWI) standard
      vendor protocols in a hospital-based prospective cohort of patients with
      transient ischemic attack (TIA) for lesion detection, lesion brightness,
      predictability of persisting infarction, and final infarct size. Methods: We
      performed 3T-magnetic resonance imaging including diffusion and T2-fluid
      attenuated inversion recovery (FLAIR) within 72 h and 8 weeks after ictus.
      Qualitative lesion brightness was assessed by visual inspection. We measured
      lesion area and brightness with manual regions of interest and compared with
      homologous normal tissue. Results: 117 patients with clinical TIA showed 78 DWI
      lesions. 2 lesions showed only on 3DWI. No lesions were uniquely 20DWI positive.
      3DWI was visually brightest for 34 lesions. 12 lesions were brightest on 20DWI.
      The median 3DWI lesion area was larger for lesions equally bright, or brightest
      on 20DWI [median (IQR) 39 (18-95) versus 18 (10-34) mm2, P = 0.007]. 3DWI showed
      highest measured relative lesion signal intensity [median (IQR) 0.77 (0.48-1.17)
      versus 0.58 (0.34-0.81), P = 0.0006]. 3DWI relative lesion signal intensity was
      not correlated to absolute signal intensity, but 20DWI performed less well for
      low-contrast lesions. 3DWI lesion size was an independent predictor of persistent
      infarction. 3-gradient direction apparent diffusion coefficient areas were
      closest to 8-week FLAIR infarct size. Conclusion: 3DWI detected more lesions and
      had higher relative lesion SI than 20DWI. 20DWI appeared blurred and did not add
      information. Clinical Trial Registration: http://www.clinicaltrials.gov. Unique
      Identifier NCT01531946.

PMID- 29326653
TI  - Electroencephalogram-Based Brain-Computer Interface and Lower-Limb Prosthesis
      Control: A Case Study.
AB  - Objective: The purpose of this study was to establish the feasibility of
      manipulating a prosthetic knee directly by using a brain-computer interface (BCI)
      system in a transfemoral amputee. Although the other forms of control could be
      more reliable and quick (e.g., electromyography control), the
      electroencephalography (EEG)-based BCI may provide amputees an alternative way to
      control a prosthesis directly from brain. Methods: A transfemoral amputee subject
      was trained to activate a knee-unlocking switch through motor imagery of the
      movement of his lower extremity. Surface scalp electrodes transmitted brain wave
      data to a software program that was keyed to activate the switch when the event
      related desynchronization in EEG reached a certain threshold. After achieving
      more than 90% reliability for switch activation by EEG rhythm-feedback training,
      the subject then progressed to activating the knee-unlocking switch on a
      prosthesis that turned on a motor and unlocked a prosthetic knee. The project
      took place in the prosthetic department of a Veterans Administration medical
      center. The subject walked back and forth in the parallel bars and unlocked the
      knee for swing phase and for sitting down. The success of knee unlocking through
      this system was measured. Additionally, the subject filled out a questionnaire on
      his experiences. Results: The success of unlocking the prosthetic knee mechanism
      ranged from 50 to 100% in eight test segments. Conclusion: The performance of the
      subject supports the feasibility for BCI control of a lower extremity prosthesis
      using surface scalp EEG electrodes. Investigating direct brain control in
      different types of patients is important to promote real-world BCI applications.

PMID- 29326655
TI  - Alterations in Mitochondrial Oxidative Stress and Mitophagy in Subjects with
      Prediabetes and Type 2 Diabetes Mellitus.
AB  - Background and aim: Hyperglycemia-mediated oxidative stress impedes cell
      reparative process like autophagy, which has been implicated in impairment of
      beta-cell function in type 2 diabetes mellitus (T2DM). However, the role of
      mitophagy (selective mitochondrial autophagy) in progression of hyperglycemia
      remains elusive. This study aimed to assess the impact of increasing severity of
      hyperglycemia on mitochondrial stress and mitophagy. Design and methods: A case
      control study included healthy controls, subjects with prediabetes, newly
      diagnosed T2DM (NDT2DM) and advanced duration of T2DM (ADT2DM) (n = 20 each).
      Mitochondrial stress indices, transcriptional and translational expression of
      mitophagy markers (PINK1, PARKIN, MFN2, NIX, LC3-II, and LAMP-2) and transmission
      electron microscopic (TEM) studies were performed in peripheral blood mononuclear
      cells. Results: With mild hyperglycemia in subjects with prediabetes, to moderate
      to severe hyperglycemia in NDT2DM and ADT2DM, a progressive rise in mitochondrial
      oxidative stress was observed. Prediabetic subjects exhibited significantly
      increased expression of mitophagy-related markers and showed a positive
      association with HOMA-beta, whereas, patients with NDT2DM and ADT2DM demonstrated
      decreased expression, with a greater decline in ADT2DM subjects. TEM studies
      revealed significantly reduced number of distorted mitochondria in prediabetics,
      as compared to the T2DM patients. In addition, receiver operating characteristic
      analysis showed HbA1C > 7% (53 mmol/mol) was associated with attenuated
      mitophagy. Conclusion: Increasing hyperglycemia is associated with progressive
      rise in oxidative stress and altered mitochondrial morphology. Sustenance of
      mitophagy at HbA1C < 7% (53 mmol/mol) strengthens the rationale of achieving
      HbA1C below this cutoff for good glycemic control. An "adaptive" increase in
      mitophagy may delay progression to T2DM by preserving the beta-cell function in
      subjects with prediabetes.

PMID- 29326654
TI  - Status Epilepticus Triggers Time-Dependent Alterations in Microglia Abundance and
      Morphological Phenotypes in the Hippocampus.
AB  - Status epilepticus (SE) is defined by the occurrence of prolonged "non-stop"
      seizures that last for at least 5 min. SE provokes inflammatory responses
      including the activation of microglial cells, the brain's resident immune cells,
      which are thought to contribute to the neuropathology and pathophysiology of
      epilepsy. Microglia are professional phagocytes that resemble peripheral
      macrophages. Upon sensing immune disturbances, including SE, microglia become
      reactive, produce inflammatory cytokines, and alter their actin cytoskeleton to
      transform from ramified to amoeboid shapes. It is widely known that SE triggers
      time-dependent microglial expression of pro-inflammatory cytokines that include
      TNFalpha and IL-1beta. However, less is known in regards to the spatiotemporal
      progression of the morphological changes, which may help define the extent of
      microglia reactivity after SE and potential function (surveillance, inflammatory,
      phagocytic). Therefore, in this study, we used the microglia/macrophage IBA1
      marker to identify and count these cells in hippocampi from control rats and at 4
      h, 3 days, and 2 weeks after a single episode of pilocarpine-induced SE. We
      identified, categorized, and counted the IBA1-positive cells with the different
      morphologies observed after SE in the hippocampal areas CA1, CA3, and dentate
      gyrus. These included ramified, hypertrophic, bushy, amoeboid, and rod. We found
      that the ramified phenotype was the most abundant in control hippocampi. In
      contrast, SE provoked time-dependent changes in the microglial morphology that
      was characterized by significant increases in the abundance of bushy-shaped cells
      at 4 h and amoeboid-shaped cells at 3 days and 2 weeks. Interestingly, a
      significant increase in the number of rod-shaped cells was only evident in the
      CA1 region at 2 weeks after SE. Taken together, these data suggest that SE
      triggers time-dependent alterations in the morphology of microglial cells. This
      detailed description of the spatiotemporal profile of SE-induced microglial
      morphological changes may help provide insight into their contribution to
      epileptogenesis.

PMID- 29326656
TI  - Variation in the Sweet Taste Receptor Gene and Dietary Intake in a Swedish Middle
      Aged Population.
AB  - Background: The preference for sweet taste is partially genetically determined.
      The major allele of the single nucleotide polymorphism rs12033832 in the sweet
      taste receptor (TAS1R2) has previously been associated with lower sugar
      sensitivity and higher sugar intake among overweight individuals. The aim of the
      present study was to examine the association between dietary intake and the
      TAS1R2 genotype in lean and overweight individuals in the population-based Malmo
      Diet and Cancer (MDC) cohort using dietary intake data with a high validity.
      Methods: In total, 3,602 participants (46-68 years old) from the MDC cohort who
      underwent baseline examinations between 1991 and 1994, who were non-smokers
      without diabetes, and for whom information regarding TAS1R2 rs7534618 (a proxy
      for rs12033832) was available were included in this study. After excluding
      individuals with potentially misreported and unstable food habits, 2,204
      individuals were retained. A modified dietary history method, including a 7-day
      food diary of prepared meals, which was specifically designed for the MDC study
      was used. Results: Only modest associations were observed between dietary intake
      and the TAS1R2 genotype. We observed slightly stronger associations after
      excluding individuals with potentially misreported and unstable food habits.
      Among the participants with a BMI >=25, the major (T) allele carriers consumed
      more carbohydrates [TT = 45.2 percentage of energy intake (E%); TG = 45.2E%; GG =
      43.7E%; p = 0.01] and less fat (p = 0.03), but these participants did not consume
      more sucrose than the G-allele carriers. No association was observed between the
      genotype and dietary intake among the participants with a BMI <25. Conclusion:
      Although the higher carbohydrate intake among the major allele carriers was
      consistent with that reported in a previous study, the magnitudes of the
      associations were substantially smaller. Because we observed no association with
      sucrose, this allele is unlikely to be useful as a marker of sugar intake in the
      MDC population.

PMID- 29326657
TI  - Early Microbes Modify Immune System Development and Metabolic Homeostasis-The
      "Restaurant" Hypothesis Revisited.
AB  - The developing infant gut microbiome affects metabolism, maturation of the
      gastrointestinal tract, immune system function, and brain development. Initial
      seeding of the neonatal microbiota occurs through maternal and environmental
      contact. Maternal diet, antibiotic use, and cesarean section alter the offspring
      microbiota composition, at least temporarily. Nutrients are thought to regulate
      initial perinatal microbial colonization, a paradigm known as the "Restaurant"
      hypothesis. This hypothesis proposes that early nutritional stresses alter both
      the initial colonizing bacteria and the development of signaling pathways
      controlled by microbial mediators. These stresses fine-tune the immune system and
      metabolic homeostasis in early life, potentially setting the stage for long-term
      metabolic and immune health. Dysbiosis, an imbalance or a maladaptation in the
      microbiota, can be caused by several factors including dietary alterations and
      antibiotics. Dysbiosis can alter biological processes in the gut and in tissues
      and organs throughout the body. Misregulated development and activity of both the
      innate and adaptive immune systems, driven by early dysbiosis, could have long
      lasting pathologic consequences such as increased autoimmunity, increased
      adiposity, and non-alcoholic fatty liver disease (NAFLD). This review will focus
      on factors during pregnancy and the neonatal period that impact a neonate's gut
      microbiome, as well as the mechanisms and possible links from early infancy that
      can drive increased risk for diseases including obesity and NAFLD. The complex
      pathways that connect diet, the microbiota, immune system development, and
      metabolism, particularly in early life, present exciting new frontiers for
      biomedical research.

PMID- 29326659
TI  - Intrauterine Reprogramming of the Polycystic Ovary Syndrome: Evidence from a
      Pilot Study of Cord Blood Global Methylation Analysis.
AB  - Polycystic ovary syndrome (PCOS) affects 5-15% of women. PCOS is a heterogeneous
      disorder displaying endocrine, metabolic, and reproductive dysfunction and
      cardiovascular risk manifestations. Evidence of heritability exists, but only a
      portion of the genetic transmission has been identified by genome-wide
      association studies and linkage studies, suggesting epigenetic phenomena may play
      a role. Evidence implicates intrauterine influences in the genesis of PCOS. This
      was a pilot study that aimed at identifying an epigenetic PCOS reprogramming
      signature by profiling the methylation of the DNA extracted from umbilical cord
      blood (UCB) from 12 subjects undergoing in vitro fertilization. Six subjects were
      anovulatory PCOS women diagnosed by Rotterdam criteria and six ovulatory non-PCOS
      women matched for age and body mass index. UCB was collected at delivery of the
      placenta; the DNA was extracted and submitted to methylation analysis. A
      differential methylation picture of prevalent hypomethylation affecting 918 genes
      was detected. Of these, 595 genes (64.8%) carried single or multiple
      hypomethylated CpG dinucleotides and 323 genes (35.2%) single or multiple
      hypermethylated CpG dinucleotides. The Ingenuity Pathway Analysis (IPA) online
      platform enlisted 908 of the 918 input genes and clustered 794 of them into 21
      gene networks. Key features of the primary networks scored by IPA included
      carbohydrate and lipid metabolism, neurotransmitter signaling, cardiovascular
      system development and function, glycosaminoglycan signaling regulation and
      control of amino acid biosynthesis. Central to the network activities were genes
      controlling hormonal regulation (ESR1), mitochondrial activity (APP, PARK2), and
      glucose metabolism (INS). Regulatory pathways such as G-protein coupled receptor
      signaling, inositol metabolism, and inflammatory response were also highlighted.
      These data suggested the existence of a putative "PCOS epigenomic superpathway"
      with three main components: glucotoxic, lipotoxic, and inflammatory. If our
      results are confirmed, they hint at an epigenetic at risk PCOS "signature" may
      thus exist that may be identifiable at birth. Additional studies are needed to
      confirm the results of this pilot study.

PMID- 29326658
TI  - Ghrelin, MicroRNAs, and Critical Limb Ischemia: Hungering for a Novel Treatment
      Option.
AB  - Critical limb ischemia (CLI) is the most severe manifestation of peripheral
      artery disease. It is characterized by chronic pain at rest, skin ulcerations,
      and gangrene tissue loss. CLI is a highly morbid condition, resulting in a
      severely diminished quality of life and a significant risk of mortality. The
      primary goal of therapy for CLI is to restore blood flow to the affected limb,
      which is only possible by surgery, but is inadvisable in up to 50% of patients.
      This subset of patients who are not candidates for revascularisation are referred
      to as "no-option" patients and are the focus of investigation for novel
      therapeutic strategies. Angiogenesis, arteriogenesis and vasculogenesis are the
      processes whereby new blood vessel networks form from the pre-existing
      vasculature and primordial cells, respectively. In therapeutic angiogenesis,
      exogenous stimulants are administered to promote angiogenesis and augment limb
      perfusion, offering a potential treatment option for "no option" patients.
      However, to date, very few clinical trials of therapeutic angiogenesis in
      patients with CLI have reported clinically significant results, and it remains a
      major challenge. Ghrelin, a 28-amino acid peptide, is emerging as a potential
      novel therapeutic for CLI. In pre-clinical models, exogenous ghrelin has been
      shown to induce therapeutic angiogenesis, promote muscle regeneration, and reduce
      oxidative stress via the modulation of microRNAs (miRs). miRs are endogenous,
      small, non-coding ribonucleic acids of ~20-22 nucleotides which regulate gene
      expression at the post-transcriptional level by either translational inhibition
      or by messenger ribonucleic acid cleavage. This review focuses on the mounting
      evidence for the use of ghrelin as a novel therapeutic for CLI, and highlights
      the miRs which orchestrate these physiological events.

PMID- 29326660
TI  - Molecular Characteristics of First IMP-4-Producing Enterobacter cloacae Sequence
      Type 74 and 194 in Korea.
AB  - The worldwide dissemination of carbapenemase-producing Enterobacteriaceae (CPE)
      has become a major therapeutic concern in clinical settings. Enterobacter cloacae
      is a major pathogen that causes serious hospital-acquired infections. We
      investigated the clinical characteristics and molecular mechanisms of the first
      IMP-4-producing E. cloacae clinical isolates in Korea. Five carbapenemase
      producing E. cloacae strains out of 792 E. cloacae clinical isolates, which have
      been identified at a university hospital in Korea between March 2014 and February
      2016, were included in this study. Antimicrobial susceptibilities to imipenem,
      meropenem, and ertapenem were tested using E-test. Carbapenemase determinant
      screening, genetic environment, and multilocus sequence typing were conducted
      using PCR and sequencing analysis. All isolates were not susceptible to at least
      one of the tested carbapenems and presented highly similar pulsed-field gel
      electrophoresis (PFGE) patterns, evidencing hospital-wide clonal dissemination.
      Among all isolates harboring the blaIMP-4 carbapenemase gene, four isolates
      identified as predominant ST74, also contained blaCMY-2. One strain, designated
      as rare ST194, carried blaCMY-1. The E. cloacae strain, harboring both blaIMP-4
      and blaCMY-1, was resistant to all three tested carbapenems. The blaIMP-4 gene
      was located on a highly mobile class 1 integron, showing a new form of the blaIMP
      4-qacG-aacA4 array. This is the first description of IMP-4-producing E. cloacae
      strains in Korea. This observation implicates the widespread of blaIMP-4 in
      Enterobacteriaceae clinical isolates and provides insights into the epidemic
      potential and clinical therapeutic importance of IMP-4-producing E. cloacae for
      healthcare-associated infections.

PMID- 29326661
TI  - En Route towards European Clinical Breakpoints for Veterinary Antimicrobial
      Susceptibility Testing: A Position Paper Explaining the VetCAST Approach.
AB  - VetCAST is the EUCAST sub-committee for Veterinary Antimicrobial Susceptibility
      Testing. Its remit is to define clinical breakpoints (CBPs) for antimicrobial
      drugs (AMDs) used in veterinary medicine in Europe. This position paper outlines
      the procedures and reviews scientific options to solve challenges for the
      determination of specific CBPs for animal species, drug substances and disease
      conditions. VetCAST will adopt EUCAST approaches: the initial step will be data
      assessment; then procedures for decisions on the CBP; and finally the release of
      recommendations for CBP implementation. The principal challenges anticipated by
      VetCAST are those associated with the differing modalities of AMD administration,
      including mass medication, specific long-acting product formulations or local
      administration. Specific challenges comprise mastitis treatment in dairy cattle,
      the range of species and within species breed considerations and several other
      variable factors not relevant to human medicine. Each CBP will be based on
      consideration of: (i) an epidemiological cut-off value (ECOFF) - the highest MIC
      that defines the upper end of the wild-type MIC distribution; (ii) a PK/PD
      breakpoint obtained from pre-clinical pharmacokinetic data [this PK/PD break
      point is the highest possible MIC for which a given percentage of animals in the
      target population achieves a critical value for the selected PK/PD index
      (fAUC/MIC or fT > MIC)] and (iii) when possible, a clinical cut-off, that is the
      relationship between MIC and clinical cure. For the latter, VetCAST acknowledges
      the paucity of such data in veterinary medicine. When a CBP cannot be
      established, VetCAST will recommend use of ECOFF as surrogate. For decision
      steps, VetCAST will follow EUCAST procedures involving transparency, consensus
      and independence. VetCAST will ensure freely available dissemination of
      information, concerning standards, guidelines, ECOFF, PK/PD breakpoints, CBPs and
      other relevant information for AST implementation. Finally, after establishing a
      CBP, VetCAST will promulgate expert comments and/or recommendations associated
      with CBPs to facilitate their sound implementation in a clinical setting.

PMID- 29326662
TI  - MgrB Alterations Mediate Colistin Resistance in Klebsiella pneumoniae Isolates
      from Iran.
AB  - Colistin is one of the last-resort therapeutic agents to combat multidrug
      resistant Gram-negative bacteria (GNB) including Klebsiella pneumoniae. Although
      it happens rarely, resistance to colistin has been reported for several GNB. A
      total of 20 colistin resistant (col-R) and three colistin susceptible (col-S)
      clinical isolates of K. pneumoniae were studied to explore the underlying
      mechanisms of colistin resistance. The presence of plasmid encoded resistance
      genes, mcr-1, mcr-2, mcr-3, and mcr-4 genes were examined by PCR. The nucleotide
      sequences of pmrA, pmrB, phoP, phoQ, and mgrB genes were determined. To evaluate
      the association between colistin resistance and upregulation of pmrHFIJKLM and
      pmrCAB operons, transcriptional level of the pmrK and pmrC genes encoding for
      lipopolysaccharide target modifying enzymes was quantified by RT-qPCR analysis.
      None of the plasmid encoded resistance genes were detected in the studied
      isolates. Inactivation of MgrB due to nonsense mutations and insertion of IS
      elements was observed in 15 col-R isolates (75%). IS elements (IS5-like and IS1
      like families) most commonly targeted the coding region and in one case the
      promoter region of the mgrB. Complementation with wild-type MgrB restored
      colistin susceptibility in isolates with altered mgrB. All col-R isolates lacked
      any genetic alterations in the pmrA, phoP, and phoQ genes and substitutions
      identified in the pmrB were not found to be involved in resistance conferring
      determined by complementation assay. Colistin resistance linked with upregulation
      of pmrHFIJKLM and pmrCAB operons with the pmrK and pmrC being overexpressed in 20
      and 11 col-R isolates, respectively. Our results demonstrated that MgrB
      alterations are the major mechanisms contributing to colistin resistance in the
      tested K. pneumoniae isolates from Iran.

PMID- 29326663
TI  - Seasonal Changes in a Maize-Based Polyculture of Central Mexico Reshape the Co
      occurrence Networks of Soil Bacterial Communities.
AB  - The milpa is a traditional maize-based polyculture in Mexico that is typically
      practiced as rainfed agriculture. Because milpa cultivation has been practiced
      over a vast range of environmental and cultural conditions, this agroecosystem is
      recognized as an important repository of biological and cultural diversity. As
      for any agroecosystem, the relationship between plant development and the
      biogeochemical processes of the soil is critical. Although the milpa has been
      studied from different perspectives, the diversity and structure of microbial
      communities within milpa soils remain largely unexplored. In this study, we
      surveyed a milpa system in Central Mexico across cropping season: before planting
      (dry season; t1), during the early growth of plants (onset of the rainy season;
      t2), and before harvest (end of the rainy season; t3). In order to examine
      changes in community structure through time, we characterized bacterial diversity
      through high-throughput sequencing of 16S rRNA gene amplicons and recorded the
      nutrient status of multiple (5-10) soil samples from our milpa plots. We
      estimated microbial diversity from a total of 90 samples and constructed co
      occurrence networks. Although we did not find significant changes in diversity or
      composition of bacterial communities across time, we identified significant
      rearrangements in their co-occurrence network structure. We found particularly
      drastic changes between the first and second time points. Co-occurrence analyses
      showed that the bacterial community changed from a less structured network at
      (t1) into modules with a non-random composition of taxonomic groups at (t2). We
      conclude that changes in bacterial communities undetected by standard diversity
      analyses can become evident when performing co-occurrence network analyses. We
      also postulate possible functional associations among keystone groups suggested
      by biogeochemical processes. This study represents the first contribution on soil
      microbial diversity of a maize-based polyculture and shows its dynamic nature in
      short-term scales.

PMID- 29326664
TI  - Molecular Epidemiology of Methicillin-Resistant Staphylococcus aureus in Horses,
      Cats, and Dogs Over a 5-Year Period in France.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) has been reported as a
      worldwide pathogen in humans and animals including companion animals, i.e., cats,
      dogs, and horses. France lacked a comprehensive nationwide study describing the
      molecular features of MRSA circulating among companion animals over a large
      period of time. Here is reported the characterization of 130 non-duplicate
      clinical MRSA isolates collected from those three animal species from 2010 to
      2015 through the French national Resapath network. Characterization of isolates
      was performed using phenotypic (antimicrobial susceptibility tests) and molecular
      (DNA arrays, spa-typing) methods. A horse-specific epidemiology was observed in
      France with the large dissemination of a unique clone, the CC398 clone harboring
      a Staphylococcal chromosomal cassette mec (SCCmec) type IV and spa-type t011. It
      was even the unique clone collected in 2015 whereas the clone CC8 USA500 (SCCmec
      type IV), classically described in horses, was present until 2014. Contrarily,
      cats and dogs were mainly infected by human-related MRSA isolates, i.e., clones
      usually reported in human infections, thus mirroring the human epidemiology in
      hospitals in France. Isolates belonging to the CC398 clone (SCCmec type IV or V)
      were also identified in 21.4% of dogs' and 26.5% of cats' MRSA isolates. In order
      to differentiate human-related from CC398 MRSA, tetracycline-resistance [or
      tet(M) detection] could be useful since this resistance is scarce in human
      related strains but constant in CC398 MRSA isolates. In all, our data give a
      nationwide epidemiological picture of MRSA in companion animals over a 5-year
      period in France, adding further epidemiological information on the contribution
      of those animal species to a major public health issue. Considering the wide
      dissemination of CC398 MRSA isolates and the fact that 11/64 (17.2%) of them
      presented the Immune Evasion Cluster which enhances CC398 capacities to colonize
      humans, a specific attention should be paid in the coming years to determine the
      risk associated to the transmission in people in frequent contacts with companion
      animals. Our data also show that the prevalence of MRSA has likely decreased in
      cats, dogs, and horses between 2012 and 2015 in France. This trend should be
      monitored in the years to come.

PMID- 29326666
TI  - Invasion by Cordgrass Increases Microbial Diversity and Alters Community
      Composition in a Mangrove Nature Reserve.
AB  - Invasion by exotic plant species can alter ecosystem function and reduce native
      plant diversity, but relatively little is known about their effects on
      belowground microbial communities. Here we investigated the effects of exotic
      cordgrass (Spartina alterniflora) invasion on the distribution of soil bacterial
      communities in a mangrove nature reserve of the Jiulong River Estuary, southeast
      China using high-throughput sequencing of 16S rRNA gene and multivariate
      statistical analysis. Our results showed that S. alterniflora invasion altered
      soil properties, and significantly increased soil bacterial taxa richness,
      primarily by stimulating an increase in conditionally rare or rare taxa, and
      changes in community composition and function. Abundant, conditionally rare and
      rare subcommunities exhibited similar response patterns to environment changes,
      with both conditionally rare and rare taxa showing a stronger response than
      abundant ones. Habitat generalists were detected among abundant, conditionally
      rare and rare taxa, whereas habitat specialists were only identified among
      conditionally rare taxa and rare taxa. In addition, we found that vegetation was
      the key factor driving these patterns. However, our comparative analysis
      indicated that both environmental selection, and neutral process, significantly
      contributed to soil bacterial community assembly. These results could improve the
      understanding of the microbial processes and mechanisms of cordgrass invasion,
      and offer empirical data of use in the restoration and management of the mangrove
      wetlands.

PMID- 29326665
TI  - Secondary Metabolites Produced during the Germination of Streptomyces coelicolor.
AB  - Spore awakening is a series of actions that starts with purely physical processes
      and continues via the launching of gene expression and metabolic activities,
      eventually achieving a vegetative phase of growth. In spore-forming
      microorganisms, the germination process is controlled by intra- and inter-species
      communication. However, in the Streptomyces clade, which is capable of developing
      a plethora of valuable compounds, the chemical signals produced during
      germination have not been systematically studied before. Our previously published
      data revealed that several secondary metabolite biosynthetic genes are expressed
      during germination. Therefore, we focus here on the secondary metabolite
      production during this developmental stage. Using high-performance liquid
      chromatography-mass spectrometry, we found that the sesquiterpenoid antibiotic
      albaflavenone, the polyketide germicidin A, and chalcone are produced during
      germination of the model streptomycete, S. coelicolor. Interestingly, the last
      two compounds revealed an inhibitory effect on the germination process. The
      secondary metabolites originating from the early stage of microbial growth may
      coordinate the development of the producer (quorum sensing) and/or play a role in
      competitive microflora repression (quorum quenching) in their nature
      environments.

PMID- 29326667
TI  - Comparative Metagenomics of Cellulose- and Poplar Hydrolysate-Degrading
      Microcosms from Gut Microflora of the Canadian Beaver (Castor canadensis) and
      North American Moose (Alces americanus) after Long-Term Enrichment.
AB  - To identify carbohydrate-active enzymes (CAZymes) that might be particularly
      relevant for wood fiber processing, we performed a comparative metagenomic
      analysis of digestive systems from Canadian beaver (Castor canadensis) and North
      American moose (Alces americanus) following 3 years of enrichment on either
      microcrystalline cellulose or poplar hydrolysate. In total, 9,386 genes encoding
      CAZymes and carbohydrate-binding modules (CBMs) were identified, with up to half
      predicted to originate from Firmicutes, Bacteroidetes, Chloroflexi, and
      Proteobacteria phyla, and up to 17% from unknown phyla. Both PCA and hierarchical
      cluster analysis distinguished the annotated glycoside hydrolase (GH)
      distributions identified herein, from those previously reported for grass-feeding
      mammals and herbivorous foragers. The CAZyme profile of moose rumen enrichments
      also differed from a recently reported moose rumen metagenome, most notably by
      the absence of GH13-appended dockerins. Consistent with substrate-driven
      convergence, CAZyme profiles from both poplar hydrolysate-fed cultures differed
      from cellulose-fed cultures, most notably by increased numbers of unique
      sequences belonging to families GH3, GH5, GH43, GH53, and CE1. Moreover, pairwise
      comparisons of moose rumen enrichments further revealed higher counts of GH127
      and CE15 families in cultures fed with poplar hydrolysate. To expand our scope to
      lesser known carbohydrate-active proteins, we identified and compared multi
      domain proteins comprising both a CBM and domain of unknown function (DUF) as
      well as proteins with unknown function within the 416 predicted polysaccharide
      utilization loci (PULs). Interestingly, DUF362, identified in iron-sulfur
      proteins, was consistently appended to CBM9; on the other hand, proteins with
      unknown function from PULs shared little identity unless from identical PULs.
      Overall, this study sheds new light on the lignocellulose degrading capabilities
      of microbes originating from digestive systems of mammals known for fiber-rich
      diets, and highlights the value of enrichment to select new CAZymes from
      metagenome sequences for future biochemical characterization.

PMID- 29326668
TI  - Transcriptome Landscape of Mycobacterium smegmatis.
AB  - The non-pathogenic bacterium Mycobacterium smegmatis mc2155 has been widely used
      as a model organism in mycobacterial research, yet a detailed study about its
      transcription landscape remains to be established. Here we report the
      transcriptome, expression profiles and transcriptional structures through growth
      phase-dependent RNA sequencing (RNA-seq) as well as other related experiments. We
      found: (1) 2,139 transcriptional start sites (TSSs) in the genome-wide scale, of
      which eight samples were randomly selected and further verified by 5'-RACE; (2)
      2,233 independent monocistronic or polycistronic mRNAs in the transcriptome
      within the operon/sub-operon structures which are classified into five groups;
      (3) 47.50% (1016/2139) genes were transcribed into leaderless mRNAs, with the
      TSSs of 41.3% (883/2139) mRNAs overlapping with the first base of the annotated
      start codon. Initial amino acids of MSMEG_4921 and MSMEG_6422 proteins were
      identified by Edman degradation, indicating the presence of distinctive
      widespread leaderless features in M. smegmatis mc2155. (4) 150 genes with
      potentially wrong structural annotation, of which 124 proposed genes have been
      corrected; (5) eight highly active promoters, with their activities further
      determined by beta-galactosidase assays. These data integrated the
      transcriptional landscape to genome information of model organism mc2155 and lay
      a solid foundation for further works in Mycobacterium.

PMID- 29326669
TI  - Yeast Monitoring of Wine Mixed or Sequential Fermentations Made by Native Strains
      from D.O. "Vinos de Madrid" Using Real-Time Quantitative PCR.
AB  - There is an increasing trend toward understanding the impact of non-Saccharomyces
      yeasts on the winemaking process. Although Saccharomyces cerevisiae is the
      predominant species at the end of fermentation, it has been recognized that the
      presence of non-Saccharomyces species during alcoholic fermentation can produce
      an improvement in the quality and complexity of the final wines. A previous work
      was developed for selecting the best combinations between S. cerevisiae and five
      non-Saccharomyces (Torulaspora delbrueckii, Schizosaccharomyces pombe, Candida
      stellata, Metschnikowia pulcherrima, and Lachancea thermotolorans) native yeast
      strains from D.O. "Vinos de Madrid" at the laboratory scale. The best inoculation
      strategies between S. cerevisiae and non-Saccharomyces strains were chosen to
      analyze, by real-time quantitative PCR (qPCR) combined with the use of specific
      primers, the dynamics of inoculated populations throughout the fermentation
      process at the pilot scale using the Malvar white grape variety. The efficiency
      of the qPCR system was verified independently of the samples matrix, founding the
      inoculated yeast species throughout alcoholic fermentation. Finally, we can
      validate the positive effect of selected co-cultures in the Malvar wine quality,
      highlighting the sequential cultures of T. delbrueckii CLI 918/S. cerevisiae CLI
      889 and C. stellata CLI 920/S. cerevisiae CLI 889 and, mixed and sequential
      cultures of L. thermotolerans 9-6C combined with S. cerevisiae CLI 889.

PMID- 29326670
TI  - Mycobacterium smegmatis PhoU Proteins Have Overlapping Functions in Phosphate
      Signaling and Are Essential.
AB  - Many bacteria regulate gene expression in response to phosphate availability
      using a two-component signal transduction system, the activity of which is
      controlled by interaction with the Pst phosphate specific transporter and a
      cytoplasmic protein PhoU. Mycobacterium tuberculosis, the causative agent of
      tuberculosis, requires its phosphate sensing signal transduction system for
      virulence and antibiotic tolerance, but the molecular mechanisms of phosphate
      sensing remain poorly characterized. M. smegmatis serves as a model for studying
      mycobacterial pathogens including M. tuberculosis. M. smegmatis encodes two
      proteins with similarity to PhoU, but it was unknown if both proteins
      participated in signal transduction with the phosphate-responsive SenX3-RegX3 two
      component system. We constructed phoU single and double deletion mutants and
      tested expression of genes in the RegX3 regulon. Only the DeltaphoU1DeltaphoU2
      mutant exhibited constitutive activation of all the RegX3-regulated genes
      examined, suggesting that M. smegmatis PhoU1 and PhoU2 have overlapping functions
      in inhibiting activity of the SenX3-RegX3 two-component system when phosphate is
      readily available. The DeltaphoU1DeltaphoU2 mutant also exhibited decreased
      tolerance to several anti-tubercular drugs. However, a complex plasmid swapping
      strategy was required to generate the DeltaphoU1DeltaphoU2 mutant, suggesting
      that either phoU1 or phoU2 is essential for in vitro growth of M. smegmatis.
      Using whole-genome sequencing, we demonstrated that all five of the
      DeltaphoU1DeltaphoU2 mutants we isolated had independent suppressor mutations
      predicted to disrupt the function of the Pst phosphate transporter, suggesting
      that in the absence of the PhoU proteins phosphate uptake by the Pst system is
      toxic. Collectively, our data demonstrate that the two M. smegmatis PhoU
      orthologs have overlapping functions in both controlling SenX3-RegX3 activity in
      response to phosphate availability and regulating phosphate transport by the Pst
      system. Our results suggest that M. smegmatis can serve as a tractable model for
      further characterization of the molecular mechanism of phosphate sensing in
      mycobacteria and to screen for compounds that would interfere with signal
      transduction and thereby increase the efficacy of existing anti-tubercular
      antibiotics.

PMID- 29326671
TI  - Specificity Characterization of SLA Class I Molecules Binding to Swine-Origin
      Viral Cytotoxic T Lymphocyte Epitope Peptides in Vitro.
AB  - Swine leukocyte antigen (SLA) class I molecules play a crucial role in generating
      specific cellular immune responses against viruses and other intracellular
      pathogens. They mainly bind and present antigens of intracellular origin to
      circulating MHC I-restricted cytotoxic T lymphocytes (CTLs). Binding of an
      appropriate epitope to an SLA class I molecule is the single most selective event
      in antigen presentation and the first step in the killing of infected cells by
      CD8+ CTLs. Moreover, the antigen epitopes are strictly restricted to specific SLA
      molecules. In this study, we constructed SLA class I complexes in vitro
      comprising viral epitope peptides, the extracellular region of the SLA-1
      molecules, and beta2-microglobulin (beta2m) using splicing overlap extension
      polymerase chain reaction (SOE-PCR). The protein complexes were induced and
      expressed in an Escherichia coli prokaryotic expression system and subsequently
      purified and refolded. Specific binding of seven SLA-1 proteins to one classical
      swine fever virus (CSFV) and four porcine reproductive and respiratory syndrome
      virus (PRRSV) epitope peptides was detected by enzyme-linked immunosorbent assay
      (ELISA)-based method. The SLA-1*13:01, SLA-1*11:10, and SLA-1*11:01:02 proteins
      were able to bind specifically to different CTL epitopes of CSFV and PRRSV and
      the MHC restrictions of the five epitopes were identified. The fixed combination
      of Asn151Val152 residues was identified as the potentially key amino acid
      residues influencing the binding of viral several CTL epitope peptides to SLA
      1*13:01 and SLA-1*04:01:01 proteins. The more flexible pocket E in the SLA
      1*13:01 protein might have fewer steric limitations and therefore be able to
      accommodate more residues of viral CTL epitope peptides, and may thus play a
      critical biochemical role in determining the peptide-binding motif of SLA
      1*13:01. Characterization of the binding specificity of peptides to SLA class I
      molecules provides an important basis for epitope studies of infectious diseases
      in swine, and for the rational development of novel porcine vaccines, as well as
      for detailed studies of CTL responses in pigs used as animal models.

PMID- 29326673
TI  - Virus Dynamics Are Influenced by Season, Tides and Advective Transport in
      Intertidal, Permeable Sediments.
AB  - Sandy surface sediments of tidal flats exhibit high microbial activity due to the
      fast and deep-reaching transport of oxygen and nutrients by porewater advection.
      On the other hand during low tide, limited transport results in nutrient and
      oxygen depletion concomitant to the accumulation of microbial metabolites. This
      study represents the first attempt to use flow-through reactors to investigate
      virus production, virus transport and the impact of tides and season in permeable
      sediments. The reactors were filled with intertidal sands of two sites (North
      beach site and backbarrier sand flat of Spiekeroog island in the German Wadden
      Sea) to best simulate advective porewater transport through the sediments. Virus
      and cell release along with oxygen consumption were measured in the effluents of
      reactors during continuous flow of water through the sediments as well as in
      tidal simulation experiments where alternating cycles with and without water flow
      (each for 6 h) were operated. The results showed net rates of virus production
      (0.3-13.2 * 106 viruses cm-3 h-1) and prokaryotic cell production (0.3-10.0 * 105
      cells cm-3 h-1) as well as oxygen consumption rates (56-737 MUmol l-1 h-1) to be
      linearly correlated reflecting differences in activity, season and location of
      the sediments. Calculations show that total virus turnover was fast with 2 to 4
      days, whereas virus-mediated cell turnover was calculated to range between 5-13
      or 33-91 days depending on the assumed burst sizes (number of viruses released
      upon cell lysis) of 14 or 100 viruses, respectively. During the experiments, the
      homogenized sediments in the reactors became vertically structured with
      decreasing microbial activities and increasing impact of viruses on prokaryotic
      mortality with depth. Tidal simulation clearly showed a strong accumulation of
      viruses and cells in the top sections of the reactors when the flow was halted
      indicating a consistently high virus production during low tide. In conclusion,
      cell lysis products due to virus production may fuel microbial communities in the
      absence of advection-driven nutrient input, but are eventually washed off the
      surface sediment during high tide and being transported into deeper sediment
      layers or into the water column together with the produced viruses.

PMID- 29326672
TI  - HHV-6A Infection of Endometrial Epithelial Cells Induces Increased Endometrial NK
      Cell-Mediated Cytotoxicity.
AB  - Background: We have recently reported the presence of Human herpesvirus-6A (HHV
      6A) DNA in the 43% of endometrial epithelial cells from primary idiopathic
      infertile women, with no positivity in fertile women. To investigate the possible
      effect of HHV-6A infection in endometrial (e)NK cells functions, we examined
      activating/inhibitory receptors expressed by eNK cells and the corresponding
      ligands on endometrial cells during HHV-6A infection. Methods: Endometrial
      biopsies and uterine flushing samples during the secretory phase were obtained
      from 20 idiopathic infertile women and twenty fertile women. HHV-6A infection of
      endometrial epithelial cells was analyzed by Real-Time PCR, immunofluorescence
      and flow cytometry. eNKs receptors and endometrial ligands expression were
      evaluated by immunofluorescence and flow cytometry. Results: We observed the
      presence of HHV-6A infection (DNA, protein) of endometrial epithelial cells in
      the 40% of idiopathic infertile women. The eNK from all the subgroups expressed
      high levels of NKG2D and NKG2A receptors. Functional studies showed that NKG2D
      activating receptor and FasL are involved in the acquired cytotoxic function of
      eNK cells during HHV-6A infection of endometrial epithelial cells. In the
      presence of HHV-6A infection, eNK cells increased expression of CCR2, CXCR3 and
      CX3CR1 chemokine receptors (p = 0.01) and endometrial epithelial cells up
      modulated the corresponding ligands: MCP1 (Monocyte chemotactic protein 1, CCL2),
      IP-10 (Interferon gamma-induced protein 10, CXCL10) and Eotaxin-3 (CCL26).
      Conclusion: Our results, for the first time, showed the implication of eNK cells
      in controlling HHV-6A endometrial infection and clarify the mechanisms that might
      be implicated in female idiopathic infertility.

PMID- 29326674
TI  - Current Insights into the Role of Rhizosphere Bacteria in Disease Suppressive
      Soils.
AB  - Disease suppressive soils offer effective protection to plants against infection
      by soil-borne pathogens, including fungi, oomycetes, bacteria, and nematodes. The
      specific disease suppression that operates in these soils is, in most cases,
      microbial in origin. Therefore, suppressive soils are considered as a rich
      resource for the discovery of beneficial microorganisms with novel antimicrobial
      and other plant protective traits. To date, several microbial genera have been
      proposed as key players in disease suppressiveness of soils, but the complexity
      of the microbial interactions as well as the underlying mechanisms and microbial
      traits remain elusive for most disease suppressive soils. Recent developments in
      next generation sequencing and other 'omics' technologies have provided new
      insights into the microbial ecology of disease suppressive soils and the
      identification of microbial consortia and traits involved in disease
      suppressiveness. Here, we review the results of recent 'omics'-based studies on
      the microbial basis of disease suppressive soils, with specific emphasis on the
      role of rhizosphere bacteria in this intriguing microbiological phenomenon.

PMID- 29326675
TI  - A Potential New Human Pathogen Belonging to Helicobacter Genus, Identified in a
      Bloodstream Infection.
AB  - We isolated from aerobic and anaerobic blood culture bottles from a febrile
      patient, a Helicobacter-like Gram negative, rod-shaped bacterium that MALDI-TOF
      MS failed to identify. Blood agar cultures incubated in a microaerobic atmosphere
      revealed a motile Gram negative rod, which was oxidase, catalase, nitrate
      reductase, esterase, and alkaline phosphatase positive. It grew at 42 degrees C
      with no detectable urease activity. Antimicrobial susceptibility testing showed
      that the organism was susceptible to beta-lactams, gentamicin, erythromycin, and
      tetracycline but resistant to ciprofloxacin. Electronic microscopy analysis
      revealed a 3 * 0.5 MUm curved rod bacterium harboring two sheathed amphitrichous
      flagella. Whole genome sequencing revealed a genome 1,708,265 base-pairs long
      with a GC content of 37.80% and a total of 1,697 coding sequences. The genomic
      analyses using the nucleotide sequences of the 16S rRNA gene, hsp60 and gyrB
      genes, as well as the GyrA protein sequence, and the results of Average
      Nucleotide Identity and in silico DNA-DNA hybridization suggest evidence for a
      novel Helicobacter species close to Helicobacter equorum and belonging to the
      group of enterohepatic Helicobacter species. As soon as the particular peptide
      mass fingerprint of this pathogen is added to the spectral databases, MALDI-TOF
      MS technology will improve its identification from clinical specimens, especially
      in case of "sterile infection". We propose to associate the present strain with
      the Latin name of the place of isolation; Caesarodunum (Tours, France) and
      suggest "Helicobacter caesarodunensis" for further description of this new
      bacterium.

PMID- 29326677
TI  - Production of HIV-1 vif mRNA Is Modulated by Natural Nucleotide Variations and
      SLSA1 RNA Structure in SA1D2prox Genomic Region.
AB  - Genomic RNA of HIV-1 contains localized structures critical for viral
      replication. Its structural analysis has demonstrated a stem-loop structure,
      SLSA1, in a nearby region of HIV-1 genomic splicing acceptor 1 (SA1). We have
      previously shown that the expression level of vif mRNA is considerably altered by
      some natural single-nucleotide variations (nSNVs) clustering in SLSA1 structure.
      In this study, besides eleven nSNVs previously identified by us, we totally found
      nine new nSNVs in the SLSA1-containing sequence from SA1, splicing donor 2, and
      through to the start codon of Vif that significantly affect the vif mRNA level,
      and designated the sequence SA1D2prox (142 nucleotides for HIV-1 NL4-3). We then
      examined by extensive variant and mutagenesis analyses how SA1D2prox sequence and
      SLSA1 secondary structure are related to vif mRNA level. While the secondary
      structure and stability of SLSA1 was largely changed by nSNVs and artificial
      mutations introduced to restore the original NL4-3 form from altered ones by
      nSNVs, no clear association of the two SLSA1 properties with vif mRNA level was
      observed. In contrast, when naturally occurring SA1D2prox sequences that contain
      multiple nSNVs were examined, we attained significant inverse correlation between
      the vif level and SLSA1 stability. These results may suggest that SA1D2prox
      sequence adapts over time, and also that the altered SA1D2prox sequence, SLSA1
      stability, and vif level are mutually related. In total, we show here that the
      entire SA1D2prox sequence and SLSA1 stability critically contribute to the
      modulation of vif mRNA level.

PMID- 29326678
TI  - Identification of the Receptor and Cellular Ortholog of the Marek's Disease Virus
      (MDV) CXC Chemokine.
AB  - Marek's disease virus (MDV) is a cell associated alphaherpesvirus that causes
      fatal lymphoma in chickens. One factor that plays a crucial role in MDV
      pathogenesis is the viral CXC chemokine vIL-8 that was originally named after
      chicken interleukin 8 (cIL-8). However, a recent study demonstrated that vIL-8
      recruits B cells and a subset of T cells but not neutrophils, suggesting that vIL
      8 is not a cIL-8 orthologue. In this study, we set to identify the cellular
      orthologues and receptor of vIL-8 using in silico analyses, binding and
      chemotaxis assays. Sequence and phylogenetic analyses of all chicken CXC
      chemokines present in the recently published chicken genome revealed that vIL-8
      shares the highest amino acid similarity with the CXCL13L1 variant. To evaluate
      if vIL-8 and CXCL13L1 are also functional orthologues, we assessed their binding
      properties and chemotaxis activity. We demonstrated that both vIL-8 and CXCL13
      variants bind B cells and subsets of T cells, confirming that they target the
      same cell types. In addition, the chemokines not only bound the target cells but
      also induced chemotaxis. Finally, we identified CXCR5 as the receptor of vIL-8
      and CXCL13 variants and confirmed that the receptor is expressed on MDV target
      cells. Taken together, our data demonstrate the conservation of the receptor
      ligand interaction between CXCR5 and CXCL13 and shed light on the origin and
      function of the MDV-encoded vIL-8 chemokine, which plays a crucial role in the
      pathogenesis of this highly oncogenic virus.

PMID- 29326676
TI  - Edible Cyanobacterial Genus Arthrospira: Actual State of the Art in Cultivation
      Methods, Genetics, and Application in Medicine.
AB  - The cyanobacterial genus Arthrospira appears very conserved and has been divided
      into five main genetic clusters on the basis of molecular taxonomy markers.
      Genetic studies of seven Arthrospira strains, including genome sequencing, have
      enabled a better understanding of those photosynthetic prokaryotes. Even though
      genetic manipulations have not yet been performed with success, many genomic and
      proteomic features such as stress adaptation, nitrogen fixation, or biofuel
      production have been characterized. Many of above-mentioned studies aimed to
      optimize the cultivation conditions. Factors like the light intensity and
      quality, the nitrogen source, or different modes of growth (auto-, hetero-, or
      mixotrophic) have been studied in detail. The scaling-up of the biomass
      production using photobioreactors, either closed or open, was also investigated
      to increase the production of useful compounds. The richness of nutrients
      contained in the genus Arthrospira can be used for promising applications in the
      biomedical domain. Ingredients such as the calcium spirulan, immulina, C
      phycocyanin, and gamma-linolenic acid (GLA) show a strong biological activity.
      Recently, its use in the fight against cancer cells was documented in many
      publications. The health-promoting action of "Spirulina" has been demonstrated in
      the case of cardiovascular diseases and age-related conditions. Some compounds
      also have potent immunomodulatory properties, promoting the growth of beneficial
      gut microflora, acting as antimicrobial and antiviral. Products derived from
      Arthrospira were shown to successfully replace biomaterial scaffolds in
      regenerative medicine. Supplementation with the cyanobacterium also improves the
      health of livestock and quality of the products of animal origin. They were also
      used in cosmetic preparations.

PMID- 29326679
TI  - The Biogeographical Distribution of Benthic Roseobacter Group Members along a
      Pacific Transect Is Structured by Nutrient Availability within the Sediments and
      Primary Production in Different Oceanic Provinces.
AB  - By now, only limited information on the Roseobacter group thriving at the
      seafloor is available. Hence, the current study was conducted to determine their
      abundance and diversity within Pacific sediments along the 180 degrees  meridian.
      We hypothesize a distinct biogeographical distribution of benthic members of the
      Roseobacter group linked to nutrient availability within the sediments and
      productivity of the water column. Lowest cell numbers were counted at the edge of
      the south Pacific gyre and within the north Pacific gyre followed by an increase
      to the north with maximum values in the highly productive Bering Sea. Specific
      quantification of the Roseobacter group revealed on average a relative abundance
      of 1.7 and 6.3% as determined by catalyzed reported deposition-fluorescence in
      situ hybridization (CARD-FISH) and quantitative PCR (qPCR), respectively.
      Corresponding Illumina tag sequencing of 16S rRNA genes and 16S rRNA transcripts
      showed different compositions containing on average 0.7 and 0.9% Roseobacter
      affiliated OTUs of the DNA- and RNA-based communities. These OTUs were mainly
      assigned to uncultured members of the Roseobacter group. Among those with
      cultured representatives, Sedimentitalea and Sulfitobacter made up the largest
      proportions. The different oceanic provinces with low nutrient content such as
      both ocean gyres were characterized by specific communities of the Roseobacter
      group, distinct from those of the more productive Pacific subarctic region and
      the Bering Sea. However, linking the community structure to specific metabolic
      processes at the seafloor is hampered by the dominance of so-far uncultured
      members of the Roseobacter group, indicating a diversity that has yet to be
      explored.

PMID- 29326680
TI  - The Mitochondrial GTPase Gem1 Contributes to the Cell Wall Stress Response and
      Invasive Growth of Candida albicans.
AB  - The interactions of mitochondria with the endoplasmic reticulum (ER) are crucial
      for maintaining proper mitochondrial morphology, function and dynamics. This
      enables cells to utilize their mitochondria optimally for energy production and
      anabolism, and it further provides for metabolic control over developmental
      decisions. In fungi, a key mechanism by which ER and mitochondria interact is via
      a membrane tether, the protein complex ERMES (ER-Mitochondria Encounter
      Structure). In the model yeast Saccharomyces cerevisiae, the mitochondrial GTPase
      Gem1 interacts with ERMES, and it has been proposed to regulate its activity.
      Here we report on the first characterization of Gem1 in a human fungal pathogen.
      We show that in Candida albicans Gem1 has a dominant role in ensuring proper
      mitochondrial morphology, and our data is consistent with Gem1 working with ERMES
      in this role. Mitochondrial respiration and steady state cellular phospholipid
      homeostasis are not impacted by inactivation of GEM1 in C. albicans. There are
      two major virulence-related consequences of disrupting mitochondrial morphology
      by GEM1 inactivation: C. albicans becomes hypersusceptible to cell wall stress,
      and is unable to grow invasively. In the gem1Delta/Delta mutant, it is
      specifically the invasive capacity of hyphae that is compromised, not the ability
      to transition from yeast to hyphal morphology, and this phenotype is shared with
      ERMES mutants. As a consequence of the hyphal invasion defect, the
      gem1Delta/Delta mutant is drastically hypovirulent in the worm infection model.
      Activation of the mitogen activated protein (MAP) kinase Cek1 is reduced in the
      gem1Delta/Delta mutant, and this function could explain both the susceptibility
      to cell wall stress and lack of invasive growth. This result establishes a new,
      respiration-independent mechanism of mitochondrial control over stress signaling
      and hyphal functions in C. albicans. We propose that ER-mitochondria interactions
      and the ER-Mitochondria Organizing Network (ERMIONE) play important roles in
      adaptive responses in fungi, in particular cell surface-related mechanisms that
      drive invasive growth and stress responsive behaviors that support fungal
      pathogenicity.

PMID- 29326681
TI  - Host Specificity for Bacterial, Archaeal and Fungal Communities Determined for
      High- and Low-Microbial Abundance Sponge Species in Two Genera.
AB  - Sponges are engaged in intimate symbioses with a diversity of microorganisms from
      all three domains of life, namely Bacteria, Archaea and Eukarya. Sponges have
      been well studied and categorized for their bacterial communities, some
      displaying a high microbial abundance (HMA), while others show low microbial
      abundance (LMA). However, the associated Archaea and Eukarya have remained
      relatively understudied. We assessed the bacterial, archaeal and eukaryotic
      diversities in the LMA sponge species Dysidea avara and Dysidea etheria by deep
      amplicon sequencing, and compared the results to those in the HMA sponges
      Aplysina aerophoba and Aplysina cauliformis. D. avara and A. aerophoba are
      sympatric in the Mediterranean Sea, while D. etheria and A. cauliformis are
      sympatric in the Caribbean Sea. The bacterial communities followed a host
      specific pattern, with host species identity explaining most of the variation
      among samples. We identified OTUs shared by the Aplysina species that support a
      more ancient association of these microbes, before the split of the two species
      studied here. These shared OTUs are suitable targets for future studies of the
      microbial traits that mediate interactions with their hosts. Even though the
      archaeal communities were not as rich as the bacterial ones, we found a
      remarkable diversification and specificity of OTUs of the family Cenarchaeaceae
      and the genus Nitrosopumilus in all four sponge species studied. Similarly, the
      differences in fungal communities were driven by sponge identity. The structures
      of the communities of small eukaryotes such as dinophytes and ciliophores
      (alveolates), and stramenopiles, could not be explained by either sponge host,
      sponge genus or geographic location. Our analyses suggest that the host
      specificity that was previously described for sponge bacterial communities also
      extends to the archaeal and fungal communities, but not to other microbial
      eukaryotes.

PMID- 29326682
TI  - Prevalence, Antibiotic Susceptibility and Diversity of Vibrio parahaemolyticus
      Isolates in Seafood from South China.
AB  - Vibrio parahaemolyticus is a leading cause of foodborne infections in China and a
      threat to human health worldwide. The main objective of this study is to
      determine the prevalence and characteristic of V. parahaemolyticus isolates in
      fish, oyster and shrimp samples from the South China domestic consumer market. To
      accomplish this, we examined 504 seafood samples from 11 provinces of China. The
      prevalence rates were 9.38, 30.36, and 25.60%, respectively. In summer (33.33%),
      the prevalence of V. parahaemolyticus was more common than that detected in the
      winter (14.01%). In addition, we identified 98 V. parahaemolyticus strains. The
      antimicrobial resistance trends of our seafood isolates to 15 antimicrobial
      agents revealed that major isolates were resistant to ampicillin (79.59%).
      Furthermore, 68.38% of the isolates were identified as being multidrug
      resistance. The prevalence of tdh or trh genes among the isolates was 8.16 and
      12.24%, respectively. ERIC-PCR and multilocus sequence typing (MLST) results
      enabled classification of the isolates (n = 98) into different clusters,
      revealing genetic variation and relatedness among the isolates. Thus, our
      findings demonstrate the prevalence of V. parahaemolyticus in a variety of common
      seafood consumed domestically in China and provides insights into the
      dissemination of antibiotic-resistant strains, which should improve our
      microbiological risk assessment knowledge associated with V. parahaemolyticus in
      seafoods.

PMID- 29326683
TI  - Role of the DNA Mismatch Repair Gene MutS4 in Driving the Evolution of
      Mycobacterium yongonense Type I via Homologous Recombination.
AB  - We recently showed that Mycobacterium yongonense could be divided into two
      genotypes: Type I, in which the rpoB gene has been transferred from Mycobacterium
      parascrofulaceum, and Type II, in which the rpoB gene has not been transferred.
      Comparative genome analysis of three M. yongonense Type I, two M. yongonense Type
      II and M. parascrofulaceum type strains were performed in this study to gain
      insight into gene transfer from M. parascrofulaceum into M. yongonense Type I
      strains. We found two genome regions transferred from M. parascrofulaceum: one
      contained 3 consecutive genes, including the rpoBC operon, and the other
      contained 57 consecutive genes that had been transferred into M. yongonense Type
      I genomes via homologous recombination. Further comparison between the M.
      yongonense Type I and II genomes revealed that Type I, but not Type II has a
      distinct DNA mismatch repair gene (MutS4 subfamily) that was possibly transferred
      via non-homologous recombination from other actinomycetes. We hypothesized that
      it could facilitate homologous recombination from the M. parascrofulaceum to the
      M. yongonense Type I genomes. We therefore generated recombinant Mycobacterium
      smegmatis containing a MutS4 operon of M. yongonense. We found that the M.
      tuberculosis rpoB fragment with a rifampin resistance-conferring mutation was
      more frequently inserted into recombinant M. smegmatis than the wild type,
      suggesting that MutS4 is a driving force in the gene transfer from M.
      parascrofulaceum to M. yongonense Type I strains via homologous recombination. In
      conclusion, our data indicated that MutS4 in M. yongonense Type I genomes may
      drive gene transfer from M. parascrofulaceum via homologous recombination,
      resulting in division of M. yongonense into two genotypes, Type I and II.

PMID- 29326684
TI  - In Situ Field Sequencing and Life Detection in Remote (79 degrees 26'N) Canadian
      High Arctic Permafrost Ice Wedge Microbial Communities.
AB  - Significant progress is being made in the development of the next generation of
      low cost life detection instrumentation with much smaller size, mass and energy
      requirements. Here, we describe in situ life detection and sequencing in the
      field in soils over laying ice wedges in polygonal permafrost terrain on Axel
      Heiberg Island, located in the Canadian high Arctic (79 degrees 26'N), an analog
      to the polygonal permafrost terrain observed on Mars. The life detection methods
      used here include (1) the cryo-iPlate for culturing microorganisms using
      diffusion of in situ nutrients into semi-solid media (2) a Microbial Activity
      Microassay (MAM) plate (BIOLOG Ecoplate) for detecting viable extant
      microorganisms through a colourimetric assay, and (3) the Oxford Nanopore MinION
      for nucleic acid detection and sequencing of environmental samples and the
      products of MAM plate and cryo-iPlate. We obtained 39 microbial isolates using
      the cryo-iPlate, which included several putatively novel strains based on the 16S
      rRNA gene, including a Pedobacter sp. (96% closest similarity in GenBank) which
      we partially genome sequenced using the MinION. The MAM plate successfully
      identified an active community capable of L-serine metabolism, which was used for
      metagenomic sequencing with the MinION to identify the active and enriched
      community. A metagenome on environmental ice wedge soil samples was completed,
      with base calling and uplink/downlink carried out via satellite internet.
      Validation of MinION sequencing using the Illumina MiSeq platform was consistent
      with the results obtained with the MinION. The instrumentation and technology
      utilized here is pre-existing, low cost, low mass, low volume, and offers the
      prospect of equipping micro-rovers and micro-penetrators with aggressive
      astrobiological capabilities. Since potentially habitable astrobiology targets
      have been identified (RSLs on Mars, near subsurface water ice on Mars, the plumes
      and oceans of Europa and Enceladus), future astrobiology missions will certainly
      target these areas and there is a need for direct life detection instrumentation.

PMID- 29326685
TI  - Forebrain Cholinergic Dysfunction and Systemic and Brain Inflammation in Murine
      Sepsis Survivors.
AB  - Sepsis, a complex disorder characterized by immune, metabolic, and neurological
      dysregulation, is the number one killer in the intensive care unit. Mortality
      remains alarmingly high even in among sepsis survivors discharged from the
      hospital. There is no clear strategy for managing this lethal chronic sepsis
      illness, which is associated with severe functional disabilities and cognitive
      deterioration. Providing insight into the underlying pathophysiology is
      desperately needed to direct new therapeutic approaches. Previous studies have
      shown that brain cholinergic signaling importantly regulates cognition and
      inflammation. Here, we studied the relationship between peripheral
      immunometabolic alterations and brain cholinergic and inflammatory states in
      mouse survivors of cecal ligation and puncture (CLP)-induced sepsis. Within 6
      days, CLP resulted in 50% mortality vs. 100% survival in sham-operated controls.
      As compared to sham controls, sepsis survivors had significantly lower body
      weight, higher serum TNF, interleukin (IL)-1beta, IL-6, CXCL1, IL-10, and HMGB1
      levels, a lower TNF response to LPS challenge, and lower serum insulin, leptin,
      and plasminogen activator inhibitor-1 levels on day 14. In the basal forebrain of
      mouse sepsis survivors, the number of cholinergic [choline acetyltransferase
      (ChAT)-positive] neurons was significantly reduced. In the hippocampus and the
      cortex of mouse sepsis survivors, the activity of acetylcholinesterase (AChE),
      the enzyme that degrades acetylcholine, as well as the expression of its encoding
      gene were significantly increased. In addition, the expression of the gene
      encoding the M1 muscarinic acetylcholine receptor was decreased in the
      hippocampus. In parallel with these forebrain cholinergic alterations, microglial
      activation (in the cortex) and increased Il1b and Il6 gene expression (in the
      cortex), and Il1b gene expression (in the hippocampus) were observed in mouse
      sepsis survivors. Furthermore, microglial activation was linked to decreased
      cortical ChAT protein expression and increased AChE activity. These results
      reinforce the notion of persistent inflammation-immunosuppression and catabolic
      syndrome in sepsis survivors and characterize a previously unrecognized
      relationship between forebrain cholinergic dysfunction and neuroinflammation in
      sepsis survivors. This insight is of interest for new therapeutic approaches that
      focus on brain cholinergic signaling for patients with chronic sepsis illness, a
      problem with no specific treatment.

PMID- 29326686
TI  - Regulation of Fn14 Receptor and NF-kappaB Underlies Inflammation in Meniere's
      Disease.
AB  - Meniere's disease (MD) is a rare disorder characterized by episodic vertigo,
      sensorineural hearing loss, tinnitus, and aural fullness. It is associated with a
      fluid imbalance between the secretion of endolymph in the cochlear duct and its
      reabsorption into the subarachnoid space, leading to an accumulation of endolymph
      in the inner ear. Epidemiological evidence, including familial aggregation,
      indicates a genetic contribution and a consistent association with autoimmune
      diseases (AD). We conducted a case-control study in two phases using an immune
      genotyping array in a total of 420 patients with bilateral MD and 1,630 controls.
      We have identified the first locus, at 6p21.33, suggesting an association with
      bilateral MD [meta-analysis leading signal rs4947296, OR = 2.089 (1.661-2.627); p
      = 1.39 * 10-09]. Gene expression profiles of homozygous genotype-selected
      peripheral blood mononuclear cells (PBMCs) demonstrated that this region is a
      trans-expression quantitative trait locus (eQTL) in PBMCs. Signaling analysis
      predicted several tumor necrosis factor-related pathways, the TWEAK/Fn14 pathway
      being the top candidate (p = 2.42 * 10-11). This pathway is involved in the
      modulation of inflammation in several human AD, including multiple sclerosis,
      systemic lupus erythematosus, or rheumatoid arthritis. In vitro studies with
      genotype-selected lymphoblastoid cells from patients with MD suggest that this
      trans-eQTL may regulate cellular proliferation in lymphoid cells through the
      TWEAK/Fn14 pathway by increasing the translation of NF-kappaB. Taken together;
      these findings suggest that the carriers of the risk genotype may develop an NF
      kappaB-mediated inflammatory response in MD.

PMID- 29326688
TI  - Cigarette Smoke Increases Endothelial CXCL16-Leukocyte CXCR6 Adhesion In Vitro
      and In Vivo. Potential Consequences in Chronic Obstructive Pulmonary Disease.
AB  - Cardiovascular disease (CVD) is a major comorbidity in chronic obstructive
      pulmonary disease (COPD). Although the mechanism of its development remains
      largely unknown, it appears to be associated with cigarette consumption and
      reduced lung function. Therefore, the aim of this study was to investigate the
      potential link between water-soluble cigarette smoke extract (CSE)-induced
      endothelial dysfunction and the function of CXCL16/CXCR6 axis on the initial
      attachment of leukocytes, in addition to its possible impact on COPD-associated
      systemic inflammation. To do this, we employed several experimental approaches,
      including RNA silencing and flow cytometry analysis, the dynamic flow chamber
      technique, and intravital microscopy in the cremasteric arterioles of animals
      exposed to cigarette smoke (CS). CSE-induced arterial CXCL16 expression, leading
      to increased platelet-leukocyte and mononuclear cell adhesiveness. CSE-induced
      CXCL16 expression was dependent on Nox5 expression and subsequent RhoA/p38
      MAPK/NF-kappaB activation. Flow cytometry analysis revealed that COPD patients (n
      = 35) presented greater numbers of activated circulating platelets (PAC-1+ and P
      selectin+) expressing CXCL16 and CXCR6 as compared with age-matched controls (n =
      17), with a higher number of CXCR6+-platelets in the smoking COPD group than in
      ex-smokers. This correlated with enhanced circulating CXCR6+-platelet-leukocyte
      aggregates in COPD patients. The increase in circulating numbers of CXCR6
      expressing platelets and mononuclear cells resulted in enhanced platelet
      leukocyte and leukocyte adhesiveness to CSE-stimulated arterial endothelium,
      which was greater than that found in age-matched controls and was partly
      dependent on endothelial CXCL16 upregulation. Furthermore, CS exposure provoked
      CXCL16-dependent leukocyte-arteriolar adhesion in cremasteric arterioles, which
      was significantly reduced in animals with a nonfunctional CXCR6 receptor. In
      conclusion, we provide the first evidence that increased numbers of CXCR6
      expressing circulating platelets and mononuclear leukocytes from patients with
      COPD might be a marker of systemic inflammation with potential consequences in
      CVD development. Accordingly, CXCL16/CXCR6 axis blockade might constitute a new
      therapeutic approach for decreasing the risk of CVD in COPD patients.

PMID- 29326690
TI  - Identifying the Presence of Prostate Cancer in Individuals with PSA Levels <20 ng
      ml-1 Using Computational Data Extraction Analysis of High Dimensional Peripheral
      Blood Flow Cytometric Phenotyping Data.
AB  - Determining whether an asymptomatic individual with Prostate-Specific Antigen
      (PSA) levels below 20 ng ml-1 has prostate cancer in the absence of definitive,
      biopsy-based evidence continues to present a significant challenge to clinicians
      who must decide whether such individuals with low PSA values have prostate
      cancer. Herein, we present an advanced computational data extraction approach
      which can identify the presence of prostate cancer in men with PSA levels <20 ng
      ml-1 on the basis of peripheral blood immune cell profiles that have been
      generated using multi-parameter flow cytometry. Statistical analysis of immune
      phenotyping datasets relating to the presence and prevalence of key leukocyte
      populations in the peripheral blood, as generated from individuals undergoing
      routine tests for prostate cancer (including tissue biopsy) using multi
      parametric flow cytometric analysis, was unable to identify significant
      relationships between leukocyte population profiles and the presence of benign
      disease (no prostate cancer) or prostate cancer. By contrast, a Genetic Algorithm
      computational approach identified a subset of five flow cytometry features
      (CD8+CD45RA-CD27-CD28- (CD8+ Effector Memory cells); CD4+CD45RA-CD27-CD28- (CD4+
      Terminally Differentiated Effector Memory Cells re-expressing CD45RA); CD3-CD19+
      (B cells); CD3+CD56+CD8+CD4+ (NKT cells)) from a set of twenty features, which
      could potentially discriminate between benign disease and prostate cancer. These
      features were used to construct a prostate cancer prediction model using the k
      Nearest-Neighbor classification algorithm. The proposed model, which takes as
      input the set of flow cytometry features, outperformed the predictive model which
      takes PSA values as input. Specifically, the flow cytometry-based model achieved
      Accuracy = 83.33%, AUC = 83.40%, and optimal ROC points of FPR = 16.13%, TPR =
      82.93%, whereas the PSA-based model achieved Accuracy = 77.78%, AUC = 76.95%, and
      optimal ROC points of FPR = 29.03%, TPR = 82.93%. Combining PSA and flow
      cytometry predictors achieved Accuracy = 79.17%, AUC = 78.17% and optimal ROC
      points of FPR = 29.03%, TPR = 85.37%. The results demonstrate the value of
      computational intelligence-based approaches for interrogating immunophenotyping
      datasets and that combining peripheral blood phenotypic profiling with PSA levels
      improves diagnostic accuracy compared to using PSA test alone. These studies also
      demonstrate that the presence of cancer is reflected in changes in the peripheral
      blood immune phenotype profile which can be identified using computational
      analysis and interpretation of complex flow cytometry datasets.

PMID- 29326689
TI  - Mesenchymal Stromal/Stem Cells: A New Era in the Cell-Based Targeted Gene Therapy
      of Cancer.
AB  - In recent years, in light of the promising potentials of mesenchymal stromal/stem
      cells (MSCs) for carrying therapeutic anticancer genes, a complete revisitation
      on old chemotherapy-based paradigms has been established. This review attempted
      to bring forward and introduce the novel therapeutic opportunities of using
      genetically engineered MSCs. The simplicities and advantages of MSCs for medical
      applications make them a unique and promising option in the case of cancer
      therapy. Some of the superiorities of using MSCs as therapeutic gene micro
      carriers are the easy cell-extraction procedures and their abundant proliferation
      capacity in vitro without losing their main biological properties. Targeted
      therapy by using MSCs as the delivery vehicles of therapeutic genes is a new
      approach in the treatment of various types of cancers. Some of the distinct
      properties of MSCs, such as tumor-tropism, non-immunogenicity, stimulatory effect
      on the anti-inflammatory molecules, inhibitory effect on inflammatory responses,
      non-toxicity against the normal tissues, and easy processes for the clinical use,
      have formed the basis of attention to MSCs. They can be easily used for the
      treatment of damaged or injured tissues, regenerative medicine, and immune
      disorders. This review focused on the drugability of MSCs and their potential for
      the delivery of candidate anticancer genes. It also briefly reviewed the vectors
      and methods used for MSC-mediated gene therapy of malignancies. Also, the
      challenges, limitations, and considerations in using MSCs for gene therapy of
      cancer and the new methods developed for resolution of these problems are
      reviewed.

PMID- 29326691
TI  - Suppression Colitis and Colitis-Associated Colon Cancer by Anti-S100a9 Antibody
      in Mice.
AB  - The association between chronic inflammation and cancer has long been recognized.
      The inflammatory bowel disease ulcerative colitis frequently progresses to colon
      cancer; however, the underlying mechanism is still unclear. S100a9 has been
      emerged as an important pro-inflammatory mediator in acute and chronic
      inflammation, and the aberrant expression of S100a9 also contributes to
      tumorigenic processes such as cell proliferation, angiogenesis, metastasis, and
      immune evasion. We previously revealed that S100a8 and S100a9 are highly
      activated and play an important role in the process of colitis-associated
      carcinogenesis, which suggests an attractive therapeutic target for ulcerative
      colitis and related colon cancer. Here, we report that administration of a
      neutralizing anti-S100a9 antibody significantly ameliorated dextran sulfate
      sodium (DSS)-induced colitis and accompanied by diminished cellular infiltrate of
      innate immunity cells (macrophages, neutrophils, and dendritic cells) and
      production of pro-inflammatory cytokines (Tnfalpha, Il1beta, Ifngamma, Il6,
      Il17a, Il23a, Il4, and Il12a). The protective effect of anti-S100a9 antibody
      treatment was also observed in azoxymethane (AOM)/DSS-induced colitis-associated
      cancer (CAC) mouse model. The inflammatory response, tumor cell proliferation,
      and immune cells infiltration in the colon tissues were suppressed by anti-S100a9
      antibody. Gene expression profiling showed that key pathways known to be involved
      in CAC development, such as Wnt signaling pathway, PI3K-Akt signaling pathway,
      cytokine-cytokine receptor interaction, and ECM-receptor interaction pathway,
      were suppressed after treatment with anti-S100a9 antibody in CAC mice. In view of
      the protective effect of neutralizing anti-S100a9 antibody against DSS-induced
      colitis and AOM/DSS-induced CAC in mouse model, this study suggests that anti
      S100a9 antibody may provide a novel therapeutic approach to treat ulcerative
      colitis and may decrease the risk for developing CAC.

PMID- 29326692
TI  - The Absence of NOD1 Enhances Killing of Aspergillus fumigatus Through Modulation
      of Dectin-1 Expression.
AB  - One of the major life-threatening infections for which severely immunocompromised
      patients are at risk is invasive aspergillosis (IA). Despite the current
      treatment options, the increasing antifungal resistance and poor outcome
      highlight the need for novel therapeutic strategies to improve outcome of
      patients with IA. In the current study, we investigated whether and how the
      intracellular pattern recognition receptor NOD1 is involved in host defense
      against Aspergillus fumigatus. When exploring the role of NOD1 in an experimental
      mouse model, we found that Nod1-/- mice were protected against IA and
      demonstrated reduced fungal outgrowth in the lungs. We found that macrophages
      derived from bone marrow of Nod1-/- mice were more efficiently inducing reactive
      oxygen species and cytokines in response to Aspergillus. Most strikingly, these
      cells were highly potent in killing A. fumigatus compared with wild-type cells.
      In line, human macrophages in which NOD1 was silenced demonstrated augmented
      Aspergillus killing and NOD1 stimulation decreased fungal killing. The
      differentially altered killing capacity of NOD1 silencing versus NOD1 activation
      was associated with alterations in dectin-1 expression, with activation of NOD1
      reducing dectin-1 expression. Furthermore, we were able to demonstrate that Nod1
      /- mice have elevated dectin-1 expression in the lung and bone marrow, and
      silencing of NOD1 gene expression in human macrophages increases dectin-1
      expression. The enhanced dectin-1 expression may be the mechanism of enhanced
      fungal killing of Nod1-/- cells and human cells in which NOD1 was silenced, since
      blockade of dectin-1 reversed the augmented killing in these cells. Collectively,
      our data demonstrate that NOD1 receptor plays an inhibitory role in the host
      defense against Aspergillus. This provides a rationale to develop novel
      immunotherapeutic strategies for treatment of aspergillosis that target the NOD1
      receptor, to enhance the efficiency of host immune cells to clear the infection
      by increasing fungal killing and cytokine responses.

PMID- 29326693
TI  - Ticks, Ixodes scapularis, Feed Repeatedly on White-Footed Mice despite Strong
      Inflammatory Response: An Expanding Paradigm for Understanding Tick-Host
      Interactions.
AB  - Ticks transmit infectious agents including bacteria, viruses and protozoa.
      However, their transmission may be compromised by host resistance to repeated
      tick feeding. Increasing host resistance to repeated tick bites is well known in
      laboratory animals, including intense inflammation at the bite sites. However, it
      is not known whether this also occurs in wild rodents such as white-footed mice,
      Peromyscus leucopus, and other wildlife, or if it occurs at all. According to the
      "host immune incompetence" hypothesis, if these mice do not have a strong
      inflammatory response, they would not reject repeated tick bites by Ixodes
      scapularis. To test this hypothesis, histopathological studies were done
      comparing dermal inflammation in P. leucopus versus guinea pigs, Cavia porcellus,
      repeatedly infested with I. scapularis. In P. leucopus, the immune cell
      composition was like that seen in laboratory mouse models, with some differences.
      However, there was a broad sessile lesion with intact dermal architecture, likely
      enabling the ticks to continue feeding unimpeded. In contrast, in C. porcellus,
      there was a relatively similar mixed cellular profile, but there also was a
      large, leukocyte-filled cavitary lesion and scab-like hyperkeratotic changes to
      the epidermal layer, along with itching and apparent pain. Ticks attached to
      sensitized C. porcellus fed poorly or were dislodged, presumably due to the
      weakened anchoring of the tick's mouthparts cemented in the heavily inflamed and
      disintegrating dermal tissues. This is the first time that the architecture of
      the skin lesions has been recognized as a major factor in understanding tick-host
      tolerance versus tick bite rejection. These findings broadly strengthen previous
      work done on lab animal models but also help explain why I. scapularis can
      repeatedly parasitize white-footed mice, supporting the "immune evasion theory"
      but cannot repeatedly parasitize other, non-permissive hosts such as guinea pigs.

PMID- 29326687
TI  - AS03- and MF59-Adjuvanted Influenza Vaccines in Children.
AB  - Influenza is a major cause of respiratory disease leading to hospitalization in
      young children. However, seasonal trivalent influenza vaccines (TIVs) have been
      shown to be ineffective and poorly immunogenic in this population. The
      development of live-attenuated influenza vaccines and adjuvanted vaccines are
      important advances in the prevention of influenza in young children. The oil-in
      water emulsions MF59 and adjuvant systems 03 (AS03) have been used as adjuvants
      in both seasonal adjuvanted trivalent influenza vaccines (ATIVs) and pandemic
      monovalent influenza vaccines. Compared with non-adjuvanted vaccine responses,
      these vaccines induce a more robust and persistent antibody response for both
      homologous and heterologous influenza strains in infants and young children.
      Evidence of a significant improvement in vaccine efficacy with these adjuvanted
      vaccines resulted in the use of the monovalent (A/H1N1) AS03-adjuvanted vaccine
      in children in the 2009 influenza pandemic and the licensure of the seasonal MF59
      ATIV for children aged 6 months to 2 years in Canada. The mechanism of action of
      MF59 and AS03 remains unclear. Adjuvants such as MF59 induce proinflammatory
      cytokines and chemokines, including CXCL10, but independently of type-1
      interferon. This proinflammatory response is associated with improved
      recruitment, activation and maturation of antigen presenting cells at the
      injection site. In young children MF59 ATIV produced more homogenous and robust
      transcriptional responses, more similar to adult-like patterns, than did TIV.
      Early gene signatures characteristic of the innate immune response, which
      correlated with antibody titers were also identified. Differences were detected
      when comparing child and adult responses including opposite trends in gene set
      enrichment at day 3 postvaccination and, unlike adult data, a lack of correlation
      between magnitude of plasmablast response at day 7 and antibody titers at day 28
      in children. These insights show the utility of novel approaches in understanding
      new adjuvants and their importance for developing improved influenza vaccines for
      children.

PMID- 29326694
TI  - The Fos-Related Antigen 1-JUNB/Activator Protein 1 Transcription Complex, a
      Downstream Target of Signal Transducer and Activator of Transcription 3, Induces
      T Helper 17 Differentiation and Promotes Experimental Autoimmune Arthritis.
AB  - Dysfunction of T helper 17 (Th17) cells leads to chronic inflammatory disorders.
      Signal transducer and activator of transcription 3 (STAT3) orchestrates the
      expression of proinflammatory cytokines and pathogenic cell differentiation from
      interleukin (IL)-17-producing Th17 cells. However, the pathways mediated by STAT3
      signaling are not fully understood. Here, we observed that Fos-related antigen 1
      (FRA1) and JUNB are directly involved in STAT3 binding to sites in the promoters
      of Fosl1 and Junb. Promoter binding increased expression of IL-17 and the
      development of Th17 cells. Overexpression of Fra1 and Junb in mice resulted in
      susceptibility to collagen-induced arthritis and an increase in Th17 cell numbers
      and inflammatory cytokine production. In patients with rheumatoid arthritis, FRA1
      and JUNB were colocalized with STAT3 in the inflamed synovium. These observations
      suggest that FRA1 and JUNB are associated closely with STAT3 activation, and that
      this activation leads to Th17 cell differentiation in autoimmune diseases and
      inflammation.

PMID- 29326696
TI  - Editorial: Natural Antibodies in Health and Disease.

PMID- 29326695
TI  - Caveolin-1 Expression Increases upon Maturation in Dendritic Cells and Promotes
      Their Migration to Lymph Nodes Thereby Favoring the Induction of CD8+ T Cell
      Responses.
AB  - Dendritic cell (DC) trafficking from peripheral tissues to lymph nodes (LNs) is a
      key step required to initiate T cell responses against pathogens as well as
      tumors. In this context, cellular membrane protrusions and the actin cytoskeleton
      are essential to guide DC migration towards chemotactic signals. Caveolin-1
      (CAV1) is a scaffolding protein that modulates signaling pathways leading to
      remodeling of the actin cytoskeleton and enhanced migration of cancer cells.
      However, whether CAV1 is relevant for DC function and specifically for DC
      migration to LNs is unknown. Here, we show that CAV1 expression is upregulated in
      DCs upon LPS- and TNF-alpha-induced maturation. CAV1 deficiency did not affect
      differentiation, maturation, or the ability of DCs to activate CD8+ T cells in
      vitro. However, CAV1-deficient (CAV1-/-) DCs displayed reduced in vivo
      trafficking to draining LNs in control and inflammatory conditions. In vitro,
      CAV1-/- DCs showed reduced directional migration in CCL21 gradients in transwell
      assays without affecting migration velocity in confined microchannels or three
      dimensional collagen matrices. In addition, CAV1-/- DCs displayed reduced
      activation of the small GTPase Rac1, a regulator of actin cytoskeletal
      remodeling, and lower numbers of F-actin-forming protrusions. Furthermore, mice
      adoptively transferred with peptide-pulsed CAV1-/- DCs showed reduced CD8+ T cell
      responses and antitumor protection. Our results suggest that CAV1 promotes the
      activation of Rac1 and the formation of membrane protrusions that favor DC
      chemotactic trafficking toward LNs where they can initiate cytotoxic T cell
      responses.

PMID- 29326697
TI  - Pacific Biosciences Sequencing and IMGT/HighV-QUEST Analysis of Full-Length
      Single Chain Fragment Variable from an In Vivo Selected Phage-Display
      Combinatorial Library.
AB  - Phage-display selection of immunoglobulin (IG) or antibody single chain Fragment
      variable (scFv) from combinatorial libraries is widely used for identifying new
      antibodies for novel targets. Next-generation sequencing (NGS) has recently
      emerged as a new method for the high throughput characterization of IG and T cell
      receptor (TR) immune repertoires both in vivo and in vitro. However, challenges
      remain for the NGS sequencing of scFv from combinatorial libraries owing to the
      scFv length (>800 bp) and the presence of two variable domains [variable heavy
      (VH) and variable light (VL) for IG] associated by a peptide linker in a single
      chain. Here, we show that single-molecule real-time (SMRT) sequencing with the
      Pacific Biosciences RS II platform allows for the generation of full-length scFv
      reads obtained from an in vivo selection of scFv-phages in an animal model of
      atherosclerosis. We first amplified the DNA of the phagemid inserts from scFv
      phages eluted from an aortic section at the third round of the in vivo selection.
      From this amplified DNA, 450,558 reads were obtained from 15 SMRT cells. Highly
      accurate circular consensus sequences from these reads were generated, filtered
      by quality and then analyzed by IMGT/HighV-QUEST with the functionality for scFv.
      Full-length scFv were identified and characterized in 348,659 reads. Full-length
      scFv sequencing is an absolute requirement for analyzing the associated VH and VL
      domains enriched during the in vivo panning rounds. In order to further validate
      the ability of SMRT sequencing to provide high quality, full-length scFv
      sequences, we tracked the reads of an scFv-phage clone P3 previously identified
      by biological assays and Sanger sequencing. Sixty P3 reads showed 100% identity
      with the full-length scFv of 767 bp, 53 of them covering the whole insert of 977
      bp, which encompassed the primer sequences. The remaining seven reads were
      identical over a shortened length of 939 bp that excludes the vicinity of primers
      at both ends. Interestingly these reads were obtained from each of the 15 SMRT
      cells. Thus, the SMRT sequencing method and the IMGT/HighV-QUEST functionality
      for scFv provides a straightforward protocol for characterization of full-length
      scFv from combinatorial phage libraries.

PMID- 29326698
TI  - CXCR1/2 Antagonism Is Protective during Influenza and Post-Influenza Pneumococcal
      Infection.
AB  - Rationale: Influenza A infections are a leading cause of morbidity and mortality
      worldwide especially when associated with secondary pneumococcal infections.
      Inflammation is important to control pathogen proliferation but may also cause
      tissue injury and death. CXCR1/2 are chemokine receptors relevant for the
      recruitment of neutrophils. We investigated the role of CXCR1/2 during influenza,
      pneumococcal, and post-influenza pneumococcal infections. Methods: Mice were
      infected with influenza A virus (IAV) or Streptococcus pneumoniae and then
      treated daily with the CXCR1/2 antagonist DF2162. To study secondary pneumococcal
      infection, mice were infected with a sublethal inoculum of IAV then infected with
      S. pneumoniae 14 days later. DF2162 was given in a therapeutic schedule from days
      3 to 6 after influenza infection. Lethality, weight loss, inflammation,
      virus/bacteria counts, and lung injury were assessed. Results: CXCL1 and CXCL2
      were produced at high levels during IAV infection. DF2162 treatment decreased
      morbidity and this was associated with decreased infiltration of neutrophils in
      the lungs and reduced pulmonary damage and viral titers. During S. pneumoniae
      infection, DF2162 treatment decreased neutrophil recruitment, pulmonary damage,
      and lethality rates, without affecting bacteria burden. Therapeutic treatment
      with DF2162 during sublethal IAV infection reduced the morbidity associated with
      virus infection and also decreased the magnitude of inflammation, lung damage,
      and number of bacteria in the blood of mice subsequently infected with S.
      pneumoniae. Conclusion: Modulation of the inflammatory response by blocking
      CXCR1/2 improves disease outcome during respiratory influenza and pneumococcal
      infections, without compromising the ability of the murine host to deal with
      infection. Altogether, inhibition of CXCR1/2 may be a valid therapeutic strategy
      for treating lung infections caused by these pathogens, especially controlling
      secondary bacterial infection after influenza.

PMID- 29326700
TI  - MTBVAC: Attenuating the Human Pathogen of Tuberculosis (TB) Toward a Promising
      Vaccine against the TB Epidemic.
AB  - Bacille Calmette-Guerin (BCG) is a live-attenuated strain of Mycobacterium bovis
      developed a century ago by repeated subculture. It remains the only vaccine
      against tuberculosis (TB) in use today, and it offers variable protection against
      the respiratory forms of TB responsible for transmission. The principal genetic
      basis for BCG attenuation is the loss of the region of difference 1 (RD1) that
      includes the genes codifying for production and export of the major virulence
      factor ESAT6. Today more than 13 TB vaccine candidates are in clinical
      evaluation. One of these candidates is MTBVAC, which is based on a rationally
      attenuated Mycobacterium tuberculosis clinical isolate belonging to modern
      lineage 4, one of the most widespread lineages among humans. MTBVAC conserves
      most of the T cell epitopes described for TB including the major immunodominant
      antigens ESAT6 and CFP10 of the RD1, deleted in BCG. After almost 20 years of
      discovery and preclinical development, MTBVAC is the only live attenuated vaccine
      based on a human pathogen that has successfully entered clinical trials as a
      preventive vaccine in newborns, aiming to replace BCG, and as a preventive
      vaccine in adolescents and adults (BCG-vaccinated at birth). Our recent
      preclinical studies have demonstrated that MTBVAC-induced immunity to ESAT6 and
      CFP10 correlate with improved efficacy relative to BCG encouraging exploration of
      these responses in human clinical trials as potential biomarkers and
      identification of these antigens as possible correlates of vaccine-induced
      protection. Such data would be extremely valuable as they would greatly
      accelerate clinical development to efficacy trials.

PMID- 29326699
TI  - Single-Domain Antibodies As Therapeutics against Human Viral Diseases.
AB  - In full-size formats, monoclonal antibodies have been highly successful as
      therapeutics against cancer and immune diseases. However, their large size leads
      to inaccessibility of some epitopes and relatively high production costs. As an
      alternative, single-domain antibodies (sdAbs) offer special advantages compared
      to full-size antibodies, including smaller size, larger number of accessible
      epitopes, relatively low production costs and improved robustness. Currently,
      sdAbs are being developed against a number of viruses, including human
      immunodeficiency virus-1 (HIV-1), influenza viruses, hepatitis C virus (HCV),
      respiratory syncytial virus (RSV), and enteric viruses. Although sdAbs are very
      potent inhibitors of viral infections, no sdAbs have been approved for clinical
      use against virial infection or any other diseases. In this review, we discuss
      the current state of research on sdAbs against viruses and their potential as
      therapeutics against human viral diseases.

PMID- 29326702
TI  - Accuracy of Programs for the Determination of Human Leukocyte Antigen Alleles
      from Next-Generation Sequencing Data.
AB  - The human leukocyte antigen (HLA) genes code for proteins that play a central
      role in the function of the immune system by presenting peptide antigens to T
      cells. As HLA genes show extremely high genetic polymorphism, HLA typing at the
      allele level is demanding and is based on DNA sequencing. Determination of HLA
      alleles is warranted as HLA alleles are major genetic risk factors in autoimmune
      diseases and are matched in transplantation. Here, we compared the accuracy of
      several published HLA-typing algorithms that are based on next-generation
      sequencing (NGS) data. As genome sequencing is becoming increasingly common in
      research, we wanted to test how well HLA alleles can be deduced from genome data
      produced in studies with objectives other than HLA typing and in platforms not
      especially designed for HLA typing. The accuracies were assessed using datasets
      consisting of NGS data produced using an in-house sequencing platform, including
      the full 4 Mbp HLA segment, from 94 stem cell transplantation patients and exome
      sequences from 63 samples of the 1000 Genomes collection. In the patient dataset,
      none of the software gave perfect results for all the samples and genes when
      programs were used with the default settings. However, we found that ensemble
      prediction of the results or modifications of the settings could be used to
      improve accuracy. For the exome-only data, most of the algorithms did not perform
      very well. The results indicate that the use of these algorithms for accurate HLA
      allele determination is not straightforward when based on NGS data not especially
      targeted to the HLA typing and their accurate use requires HLA expertise.

PMID- 29326701
TI  - Life and Death of Activated T Cells: How Are They Different from Naive T Cells?
AB  - T cells are pivotal in immunity and immunopathology. After activation, T cells
      undergo a clonal expansion and differentiation followed by a contraction phase,
      once the pathogen has been cleared. Cell survival and cell death are critical for
      controlling the numbers of naive T cells, effector, and memory T cells. While
      naive T cell survival has been studied for a long time, more effort has gone into
      understanding the survival and death of activated T cells. Despite this effort,
      there is still much to be learnt about T cell survival, as T cells transition
      from naive to effector to memory. One key advance is the development of
      inhibitors that may allow the temporal study of survival mechanisms operating in
      these distinct cell states. Naive T cells were highly reliant on BCL-2 and
      sensitive to BCL-2 inhibition. Activated T cells are remarkably different in
      their regulation of apoptosis by pro- and antiapoptotic members of the BCL-2
      family, rendering them differentially sensitive to antagonists blocking the
      function of one or more members of this family. Recent progress in understanding
      other programmed cell death mechanisms, especially necroptosis, suggests a unique
      role for alternative pathways in regulating death of activated T cells.
      Furthermore, we highlight a mechanism of epigenetic regulation of cell survival
      unique to activated T cells. Together, we present an update of our current
      understanding of the survival requirement of activated T cells.

PMID- 29326703
TI  - Both Systemic and Intra-articular Immunization with Citrullinated Peptides Are
      Needed to Induce Arthritis in the Macaque.
AB  - Objectives: Anti-citrullinated peptides antibodies (ACPAs) have high specificity
      for the diagnosis of rheumatoid arthritis (RA), but their role in the
      pathophysiology is not fully established. The main genetic risk factor for RA,
      the shared epitope in major histocompatibility complex class II, is associated
      with ACPAs. Among certain non-human primates, 8% carry the shared epitope called
      H6 haplotype, and being similar to humans, are ideal candidates to study the role
      of ACPAs in RA. The goal of this study was to develop a macaque model of RA based
      on immunization against citrullinated peptides to generate an ACPA-mediated model
      of arthritis. Methods: Cynomolgus macaques were immunized with four citrullinated
      peptides from vimentin, fibrinogen, and aggrecan, known to induce T-cell response
      in RA patients, and received an intra-articular (IA) boost with the same four
      citrullinated peptides pooled. Results: In the macaque, the T-cell response was
      specific to citrullinated peptides. Antibodies generated in response to
      immunization were cross-reactive between the citrulline and arginine peptides.
      The presence of the H6 haplotype did not affect the magnitude of the immune
      response. Since no clinical response was observed, macaques received an IA boost
      with the same four peptides pooled and incomplete Freund's adjuvant, which led to
      a prolonged neutrophil-rich mono-arthritis, preferentially in H6-positive
      animals. Conversely, animals boosted with incomplete Freund's adjuvant alone
      presented only transient mono-arthritis. Conclusion: This two-hit model of
      prolonged mono-arthritis mimics what could happen in RA. Despite the limited
      number of joints with disease in the macaque model, the model appears unique to
      study the events occurring during the preclinical phase of RA, from immunization
      against citrullinated peptides to the clinical appearance of disease.

PMID- 29326705
TI  - Mycobacterium tuberculosis Modulates miR-106b-5p to Control Cathepsin S
      Expression Resulting in Higher Pathogen Survival and Poor T-Cell Activation.
AB  - The success of tuberculosis (TB) bacillus, Mycobacterium tuberculosis (Mtb),
      relies on the ability to survive in host cells and escape to immune surveillance
      and activation. We recently demonstrated that Mtb manipulation of host lysosomal
      cathepsins in macrophages leads to decreased enzymatic activity and pathogen
      survival. In addition, while searching for microRNAs (miRNAs) involved in
      posttranscriptional gene regulation during mycobacteria infection of human
      macrophages, we found that selected miRNAs such as miR-106b-5p were specifically
      upregulated by pathogenic mycobacteria. Here, we show that miR-106b-5p is
      actively manipulated by Mtb to ensure its survival in macrophages. Using an in
      silico prediction approach, we identified miR-106b-5p with a potential binding to
      the 3'-untranslated region of cathepsin S (CtsS) mRNA. We demonstrated by
      luminescence-based methods that miR-106b-5p indeed targets CTSS mRNA resulting in
      protein translation silencing. Moreover, miR-106b-5p gain-of-function experiments
      lead to a decreased CtsS expression favoring Mtb intracellular survival. By
      contrast, miR-106b-5p loss-of-function in infected cells was concomitant with
      increased CtsS expression, with significant intracellular killing of Mtb and T
      cell activation. Modulation of miR-106b-5p did not impact necrosis, apoptosis or
      autophagy arguing that miR-106b-5p directly targeted CtsS expression as a way for
      Mtb to avoid exposure to degradative enzymes in the endocytic pathway.
      Altogether, our data suggest that manipulation of miR-106b-5p as a potential
      target for host-directed therapy for Mtb infection.

PMID- 29326706
TI  - Targeting and Recognition of Toll-Like Receptors by Plant and Pathogen Lectins.
AB  - We have reported that some lectins act as agonists of toll-like receptors (TLRs)
      and have immunomodulatory properties. The plant lectin ArtinM, for example,
      interacts with N-glycans of TLR2, whereas other lectins of microbial origin
      interact with TLR2 and TLR4. Expression of the receptors on the surface of
      antigen-presenting cells exposes N-glycans that may be targeted by lectins of
      different structures, specificities, and origins. In vitro, these interactions
      trigger cell signaling that leads to NF-kappaB activation and production of the
      Th1 polarizing cytokine IL-12. In vivo, a same sequence of events follows the
      administration of an active lectin to mice infected with an intracellular
      pathogen, conferring resistance to the pathogen. The lectins of the human
      pathogens Toxoplasma gondii (TgMIC1 and TgMIC4) and Paracoccidioides brasiliensis
      (Paracoccin), by recognition and activation of TLR2 and TLR4, induce cell events
      and in vivo effects comparable to the promoted by the plant lectin ArtinM. In
      this article, we highlight these two distinct mechanisms for activating antigen
      presenting cells. On the one hand, TLRs act as sensors for the presence of
      conventional pathogen-associated molecular patterns, such as microbial lipids. On
      the other hand, we showed that TLR-mediated cell activation might be triggered by
      an alternative way, in which lectins bind to TLRs N-glycans and stimulate cells
      to increase the expression of pro-inflammatory cytokines. This process may lead
      to the development of new pharmaceutical tools that promote protective immune
      responses directed against intracellular pathogens and tumors.

PMID- 29326704
TI  - Innate Lymphoid Cells in HIV/SIV Infections.
AB  - Over the past several years, new populations of innate lymphocytes have been
      described in mice and primates that are critical for mucosal homeostasis,
      microbial regulation, and immune defense. Generally conserved from mice to
      humans, innate lymphoid cells (ILC) have been divided primarily into three
      subpopulations based on phenotypic and functional repertoires: ILC1 bear
      similarities to natural killer cells; ILC2 have overlapping functions with TH2
      cells; and ILC3 that share many functions with TH17/TH22 cells. ILC are
      specifically enriched at mucosal surfaces and are possibly one of the earliest
      responders during viral infections besides being involved in the homeostasis of
      gut-associated lymphoid tissue and maintenance of gut epithelial barrier
      integrity. Burgeoning evidence also suggests that there is an early and sustained
      abrogation of ILC function and numbers during HIV and pathogenic SIV infections,
      most notably ILC3 in the gastrointestinal tract, which leads to disruption of the
      mucosal barrier and dysregulation of the local immune system. A better
      understanding of the direct or indirect mechanisms of loss and dysfunction will
      be critical to immunotherapeutics aimed at restoring these cells. Herein, we
      review the current literature on ILC with a particular emphasis on ILC3 and their
      role(s) in mucosal immunology and the significance of disrupting the ILC niche
      during HIV and SIV infections.

PMID- 29326707
TI  - Extensive Basal Level Activation of Complement Mannose-Binding Lectin-Associated
      Serine Protease-3: Kinetic Modeling of Lectin Pathway Activation Provides
      Possible Mechanism.
AB  - Serine proteases (SPs) are typically synthesized as precursors, termed proenzymes
      or zymogens, and the fully active form is produced via limited proteolysis by
      another protease or by autoactivation. The lectin pathway of the complement
      system is initiated by mannose-binding lectin (MBL)-associated SPs (MASP)-1, and
      MASP-2, which are known to be present as proenzymes in blood. The third SP of the
      lectin pathway, MASP-3, was recently shown to be the major activator, and the
      exclusive "resting blood" activator of profactor D, producing factor D, the
      initiator protease of the alternative pathway. Because only activated MASP-3 is
      capable of carrying out this cleavage, it was presumed that a significant
      fraction of MASP-3 must be present in the active form in resting blood. Here, we
      aimed to detect active MASP-3 in the blood by a more direct technique and to
      quantitate the active to zymogen ratio. First, MASPs were partially purified
      (enriched) from human plasma samples by affinity chromatography using immobilized
      MBL in the presence of inhibitors. Using this MASP pool, only the zymogen form of
      MASP-1 was detected by Western blot, whereas over 70% MASP-3 was in an activated
      form in the same samples. Furthermore, the active to zymogen ratio of MASP-3
      showed little individual variation. It is enigmatic how MASP-3, which is not able
      to autoactivate, is present mostly as an active enzyme, whereas MASP-1, which has
      a potent autoactivation capability, is predominantly proenzymic in resting blood.
      In an attempt to explain this phenomenon, we modeled the basal level fluid-phase
      activation of lectin pathway proteases and their subsequent inactivation by C1
      inhibitor and antithrombin using available and newly determined kinetic
      constants. The model can explain extensive MASP-3 activation only if we assume
      efficient intracomplex activation of MASP-3 by zymogen MASP-1. On the other hand,
      the model is in good agreement with the fact that MASP-1 and -2 are predominantly
      proenzymic and some of them is present in the form of inactive serpin-protease
      complexes. As an alternative hypothesis, MASP-3 activation by proprotein
      convertases is also discussed.

PMID- 29326708
TI  - High Amounts of S100-Alarmins Confer Antimicrobial Activity on Human Breast Milk
      Targeting Pathogens Relevant in Neonatal Sepsis.
AB  - Sepsis is a leading cause of perinatal mortality worldwide. Breast milk (BM)
      feeding is protective against neonatal sepsis, but the molecular mechanisms
      remain unexplained. Despite various supplementations with potential bioactive
      components from BM formula feeding cannot protect from sepsis. S100-alarmins are
      important immunoregulators in newborns preventing excessive inflammation. At high
      concentrations, the S100A8/A9 protein complex also has antimicrobial properties
      due to its metal ion chelation capacity. To assess whether BM contains S100
      alarmins that might mediate the sepsis-protective effect of BM 97 human BM
      samples stratified for gestational age, mode of delivery and sampling after birth
      were collected and analyzed. S100A8/A9 levels were massively elevated after birth
      (p < 0.0005). They slowly decreased during the first month of life, then reaching
      levels comparable to normal values in adult serum. The concentration of S100A8/A9
      in BM was significantly higher after term compared with preterm birth (extremely
      preterm, p < 0.005; moderate preterm, p < 0.05) and after vaginal delivery
      compared with cesarean section (p < 0.0005). In newborn s100a9-/- mice, enterally
      supplied S100-alarmins could be retrieved systemically in the plasma. To explore
      the antimicrobial activity against common causal pathogens of neonatal sepsis,
      purified S100-alarmins and unmodified as well as S100A8/A9-depleted BM were used
      in growth inhibition tests. The high amount of S100A8/A9 proved to be an
      important mediator of the antimicrobial activity of BM, especially inhibiting the
      growth of manganese (Mn) sensitive bacteria such as Staphylococcus aureus (p <
      0.00005) and group B streptococci (p < 0.005). Depletion of S100A8/A9
      significantly reduced this effect (p < 0.05, respectively). The growth of
      Escherichia coli was also inhibited by BM (p < 0.00005) as well as by S100A8/A9
      in culture assays (p < 0.05). But its growth in BM remained unaffected by the
      removal of S100A8/A9 and was neither dependent on Mn suggesting that the
      antimicrobial effects of S100A8/A9 in BM are primarily mediated by its Mn
      chelating capacity. In summary, the enteral supply of bioavailable,
      antimicrobially active amounts of S100-alarmins might be a promising option to
      protect newborns at high risk from infections and sepsis.

PMID- 29326709
TI  - End-Stage Renal Disease Causes Skewing in the TCR Vbeta-Repertoire Primarily
      within CD8+ T Cell Subsets.
AB  - A broad T cell receptor (TCR-) repertoire is required for an effective immune
      response. TCR-repertoire diversity declines with age. End-stage renal disease
      (ESRD) patients have a prematurely aged T cell system which is associated with
      defective T cell-mediated immunity. Recently, we showed that ESRD may
      significantly skew the TCR Vbeta-repertoire. Here, we assessed the impact of ESRD
      on the TCR Vbeta-repertoire within different T cell subsets using a
      multiparameter flow-cytometry-based assay, controlling for effects of aging and
      CMV latency. Percentages of 24 different TCR Vbeta-families were tested in
      circulating naive and memory T cell subsets of 10 ESRD patients and 10 age- and
      CMV-serostatus-matched healthy individuals (HI). The Gini-index, a parameter used
      in economics to describe the distribution of income, was calculated to determine
      the extent of skewing at the subset level taking into account frequencies of all
      24 TCR Vbeta-families. In addition, using HI as reference population, the
      differential impact of ESRD was assessed on clonal expansion at the level of an
      individual TCR Vbeta-family. CD8+, but not CD4+, T cell differentiation was
      associated with higher Gini-TCR indices. Gini-TCR indices were already
      significantly higher for different CD8+ memory T cell subsets of younger ESRD
      patients compared to their age-matched HI. ESRD induced expansions of not one TCR
      Vbeta-family in particular and expansions were predominantly observed within the
      CD8+ T cell compartment. All ESRD patients had expanded TCR Vbeta-families within
      total CD8+ T cells and the median (IQ range) number of expanded TCR Vbeta
      families/patient amounted to 2 (1-4). Interestingly, ESRD also induced clonal
      expansions of TCR Vbeta-families within naive CD8+ T cells as 8 out of 10
      patients had expanded TCR Vbeta-families. The median (IQ range) number of
      expanded families/patient amounted to 1 (1-1) within naive CD8+ T cells. In
      conclusion, loss of renal function skews the TCR Vbeta-repertoire already in
      younger patients by inducing expansions of different TCR Vbeta-families within
      the various T cell subsets, primarily affecting the CD8+ T cell compartment. This
      skewed TCR Vbeta-repertoire may be associated with a less broad and diverse T
      cell-mediated immunity.

PMID- 29326710
TI  - Ubiquitin-Specific Protease 14 Negatively Regulates Toll-Like Receptor 4-Mediated
      Signaling and Autophagy Induction by Inhibiting Ubiquitination of TAK1-Binding
      Protein 2 and Beclin 1.
AB  - Ubiquitin-specific protease 14 (USP14), one of three proteasome-associated
      deubiquitinating enzymes, has multifunctional roles in cellular context. Here, we
      report a novel molecular mechanism and function of USP14 in regulating autophagy
      induction and nuclear factor-kappa B (NF-kappaB) activation induced by toll-like
      receptor (TLR) 4 (TLR4). USP14 interacted with tumor necrosis factor (TNF)
      receptor-associated factor 6 (TRAF6) and interrupted the association of Beclin 1
      with TRAF6, leading to inhibition of TRAF6-mediated ubiquitination of Beclin 1.
      Reduced expression of USP14 in USP14-knockdown (USP14KD) THP-1 cells enhanced
      autophagy induction upon TLR4 stimulation as shown by the increased conversion of
      cytosolic LC3-I to membrane-bound LC3-II. Moreover, USP14KD human breast
      carcinoma MDA-MB-231 cells and USP14KD human hepatic adenocarcinoma SK-HEP-1
      cells showed increased cell migration and invasion, indicating that USP14 is
      negatively implicated in the cancer progression by the inhibition of autophagy
      induction. Furthermore, we found that USP14 interacted with TAK1-binding protein
      (TAB) 2 protein and induced deubiquitination of TAB 2, a key factor in the
      activation of NF-kappaB. Functionally, overexpression of USP14 suppressed TLR4
      induced activation of NF-kappaB. In contrast, USP14KD THP-1 cells showed enhanced
      activation of NF-kappaB, NF-kappaB-dependent gene expression, and production of
      pro-inflammatory cytokines such as IL-6, IL-1beta, and tumor necrosis factor
      alpha. Taken together, our data demonstrate that USP14 can negatively regulate
      autophagy induction by inhibiting Beclin 1 ubiquitination, interrupting
      association between TRAF6 and Beclin 1, and affecting TLR4-induced activation of
      NF-kappaB through deubiquitination of TAB 2 protein.

PMID- 29326711
TI  - Harnessing the Power of Invariant Natural Killer T Cells in Cancer Immunotherapy.
AB  - Invariant natural killer T (iNKT) cells are a distinct subset of innate-like
      lymphocytes bearing an invariant T-cell receptor, through which they recognize
      lipid antigens presented by monomorphic CD1d molecules. Upon activation, iNKT
      cells are capable of not only having a direct effector function but also
      transactivating NK cells, maturing dendritic cells, and activating B cells,
      through secretion of several cytokines and cognate TCR-CD1d interaction. Endowed
      with the ability to orchestrate an all-encompassing immune response, iNKT cells
      are critical in shaping immune responses against pathogens and cancer cells. In
      this review, we examine the critical role of iNKT cells in antitumor responses
      from two perspectives: (i) how iNKT cells potentiate antitumor immunity and (ii)
      how CD1d+ tumor cells may modulate their own expression of CD1d molecules. We
      further explore hypotheses to explain iNKT cell activation in the context of
      cancer and how the antitumor effects of iNKT cells can be exploited in different
      forms of cancer immunotherapy, including their role in the development of cancer
      vaccines.

PMID- 29326712
TI  - Autophagy: A Potential Therapeutic Target for Reversing Sepsis-Induced
      Immunosuppression.
AB  - Sepsis remains the leading cause of mortality in intensive care units and an
      intractable condition due to uncontrolled inflammation together with immune
      suppression. Dysfunction of immune cells is considered as a major cause for poor
      outcome of septic patients but with little specific treatments. Currently,
      autophagy that is recognized as an important self-protective mechanism for
      cellular survival exhibits great potential for maintaining immune homeostasis and
      alleviating multiple organ failure, which further improves survival of septic
      animals. The protective effect of autophagy on immune cells covers both innate
      and adaptive immune responses and refers to various cellular receptors and
      intracellular signaling. Multiple drugs and measures are reportedly beneficial
      for septic challenge by inducing autophagy process. Therefore, autophagy might be
      an effective target for reversing immunosuppression compromised by sepsis.

PMID- 29326714
TI  - Mucosal-Associated Invariant T Cell Interactions with Commensal and Pathogenic
      Bacteria: Potential Role in Antimicrobial Immunity in the Child.
AB  - Mucosal-associated invariant T (MAIT) cells are unconventional CD3+CD161high T
      lymphocytes that recognize vitamin B2 (riboflavin) biosynthesis precursor
      derivatives presented by the MHC-I related protein, MR1. In humans, their T cell
      receptor is composed of a Valpha7.2-Jalpha33/20/12 chain, combined with a
      restricted set of Vbeta chains. MAIT cells are very abundant in the liver (up to
      40% of resident T cells) and in mucosal tissues, such as the lung and gut. In
      adult peripheral blood, they represent up to 10% of circulating T cells, whereas
      they are very few in cord blood. This large number of MAIT cells in the adult
      likely results from their gradual expansion with age following repeated
      encounters with riboflavin-producing microbes. Upon recognition of MR1 ligands,
      MAIT cells have the capacity to rapidly eliminate bacterially infected cells
      through the production of inflammatory cytokines (IFNgamma, TNFalpha, and IL-17)
      and cytotoxic effector molecules (perforin and granzyme B). Thus, MAIT cells may
      play a crucial role in antimicrobial defense, in particular at mucosal sites. In
      addition, MAIT cells have been implicated in diseases of non-microbial etiology,
      including autoimmunity and other inflammatory diseases. Although their
      participation in various clinical settings has received increased attention in
      adults, data in children are scarce. Due to their innate-like characteristics,
      MAIT cells might be particularly important to control microbial infections in the
      young age, when long-term protective adaptive immunity is not fully developed.
      Herein, we review the data showing how MAIT cells may control microbial
      infections and how they discriminate pathogens from commensals, with a focus on
      models relevant for childhood infections.

PMID- 29326715
TI  - Transcriptomics in Human Challenge Models.
AB  - Human challenge models, in which volunteers are experimentally infected with a
      pathogen of interest, provide the opportunity to directly identify both natural
      and vaccine-induced correlates of protection. In this review, we highlight how
      the application of transcriptomics to human challenge studies allows for the
      identification of novel correlates and gives insight into the immunological
      pathways required to develop functional immunity. In malaria challenge trials for
      example, innate immune pathways appear to play a previously underappreciated role
      in conferring protective immunity. Transcriptomic analyses of samples obtained in
      human challenge studies can also deepen our understanding of the immune responses
      preceding symptom onset, allowing characterization of innate immunity and early
      gene signatures, which may influence disease outcome. Influenza challenge studies
      demonstrate that these gene signatures have diagnostic potential in the context
      of pandemics, in which presymptomatic diagnosis of at-risk individuals could
      allow early initiation of antiviral treatment and help limit transmission.
      Furthermore, gene expression analysis facilitates the identification of host
      factors contributing to disease susceptibility, such as C4BPA expression in
      enterotoxigenic Escherichia coli infection. Overall, these studies highlight the
      exceptional value of transcriptional data generated in human challenge trials and
      illustrate the broad impact molecular data analysis may have on global health
      through rational vaccine design and biomarker discovery.

PMID- 29326716
TI  - Interleukin-6 Trans-Signaling Pathway Promotes Immunosuppressive Myeloid-Derived
      Suppressor Cells via Suppression of Suppressor of Cytokine Signaling 3 in Breast
      Cancer.
AB  - Interleukin-6 (IL-6) has been reported to stimulate myeloid-derived suppressor
      cells (MDSCs) in multiple cancers, but the molecular events involved in this
      process are not completely understood. We previously found that cancer-derived IL
      6 induces T cell suppression of MDSCs in vitro via the activation of STAT3/IDO
      signaling pathway. In this study, we aimed to elucidate the underlying
      mechanisms. We found that in primary breast cancer tissues, cancer-derived IL-6
      was positively correlated with infiltration of MDSCs in situ, which was
      accompanied by more aggressive tumor phenotypes and worse clinical outcomes. In
      vitro IL-6 stimulated the amplification of MDSCs and promoted their T cell
      suppression ability, which were fully inhibited by an IL-6-specific blocking
      antibody. Our results demonstrate that IL-6-dependent suppressor of cytokine
      signaling 3 (SOCS3) suppression in MDSCs induced phosphorylation of the JAK1,
      JAK2, TYK2, STAT1, and STAT3 proteins, which was correlated with T cell
      suppression of MDSCs in vitro. Therefore, dysfunction in the SOCS feedback loop
      promoted long-term activation of the JAK/STAT signaling pathway and predominantly
      contributed to IL-6-mediated effects on MDSCs. Furthermore, IL-6-induced
      inhibition of SOCS3 and activation of the JAK/STAT pathway was correlated with an
      elevated expression of IL-6 receptor alpha (CD126), in which the soluble CD126
      mediated IL-6 trans-signaling pathway significantly regulated IL-6-mediated
      effects on MDSCs. Finally, IL-6-induced SOCS3 dysfunction and sustained
      activation of the JAK/STAT signaling pathway promoted the amplification and
      immunosuppressive function of breast cancer MDSCs in vitro and in vivo, and thus
      blocking the IL-6 signaling pathway is a promising therapeutic strategy for
      eliminating and inhibiting MDSCs to improve prognosis.

PMID- 29326713
TI  - Macrophage-Bacteria Interactions-A Lipid-Centric Relationship.
AB  - Macrophages are professional phagocytes at the front line of immune defenses
      against foreign bodies and microbial pathogens. Various bacteria, which are
      responsible for deadly diseases including tuberculosis and salmonellosis, are
      capable of hijacking this important immune cell type and thrive intracellularly,
      either in the cytoplasm or in specialized vacuoles. Tight regulation of cellular
      metabolism is critical in shaping the macrophage polarization states and immune
      functions. Lipids, besides being the bulk component of biological membranes,
      serve as energy sources as well as signaling molecules during infection and
      inflammation. With the advent of systems-scale analyses of genes, transcripts,
      proteins, and metabolites, in combination with classical biology, it is
      increasingly evident that macrophages undergo extensive lipid remodeling during
      activation and infection. Each bacterium species has evolved its own tactics to
      manipulate host metabolism toward its own advantage. Furthermore, modulation of
      host lipid metabolism affects disease susceptibility and outcome of infections,
      highlighting the critical roles of lipids in infectious diseases. Here, we will
      review the emerging roles of lipids in the complex host-pathogen relationship and
      discuss recent methodologies employed to probe these versatile metabolites during
      the infection process. An improved understanding of the lipid-centric nature of
      infections can lead to the identification of the Achilles' heel of the pathogens
      and host-directed targets for therapeutic interventions. Currently, lipid
      moderating drugs are clinically available for a range of non-communicable
      diseases, which we anticipate can potentially be tapped into for various
      infections.

PMID- 29326717
TI  - Long-Lasting Graft-Derived Donor T Cells Contribute to the Pathogenesis of
      Chronic Graft-versus-Host Disease in Mice.
AB  - Chronic graft-versus-host disease (cGVHD) is a major complication in long-term
      survivors of allogeneic hematopoietic stem cell transplantation (allo-HSCT).
      Graft-derived T cells (TG) have been implicated in the induction of cGVHD;
      however, the extent of their contribution to the pathogenesis of cGVHD remains
      unclear. Using a mouse model of cGVHD, we demonstrate that TG predominate over
      hematopoietic stem cell-derived T cells generated de novo (THSC) in cGVHD
      affected organs such as the liver and lung even at day 63 after allo-HSCT.
      Persisting TG, in particular CD8+ TG, not only displayed an exhausted or
      senescent phenotype but also contained a substantial proportion of cells that had
      the potential to proliferate and produce inflammatory cytokines. Host antigens
      indirectly presented by donor HSC-derived hematopoietic cells were involved in
      the maintenance of TG in the reconstituted host. Selective depletion of TG in the
      chronic phase of disease resulted in the expansion of THSC and thus neither the
      survival nor histopathology of cGVHD was ameliorated. On the other hand, THSC
      depletion caused activation of TG and resulted in a lethal TG-mediated
      exacerbation of GVHD. The findings presented here clarify the pathological role
      of long-lasting TG in cGVHD.

PMID- 29326718
TI  - Deletion of TGF-beta1 Increases Bacterial Clearance by Cytotoxic T Cells in a
      Tuberculosis Granuloma Model.
AB  - Mycobacterium tuberculosis is the pathogenic bacterium that causes tuberculosis
      (TB), one of the most lethal infectious diseases in the world. The only vaccine
      against TB is minimally protective, and multi-drug resistant TB necessitates new
      therapeutics to treat infection. Developing new therapies requires a better
      understanding of the complex host immune response to infection, including
      dissecting the processes leading to formation of granulomas, the dense cellular
      lesions associated with TB. In this work, we pair experimental and computational
      modeling studies to explore cytokine regulation in the context of TB. We use our
      next-generation hybrid multi-scale model of granuloma formation (GranSim) to
      capture molecular, cellular, and tissue scale dynamics of granuloma formation. We
      identify TGF-beta1 as a major inhibitor of cytotoxic T-cell effector function in
      granulomas. Deletion of TGF-beta1 from the system results in improved bacterial
      clearance and lesion sterilization. We also identify a novel dichotomous
      regulation of cytotoxic T cells and macrophages by TGF-beta1 and IL-10,
      respectively. These findings suggest that increasing cytotoxic T-cell effector
      functions may increase bacterial clearance in granulomas and highlight potential
      new therapeutic targets for treating TB.

PMID- 29326720
TI  - Improved Cytotoxic T Lymphocyte Responses to Vaccination with Porcine
      Reproductive and Respiratory Syndrome Virus in 4-1BB Transgenic Pigs.
AB  - Vaccination is the most reliable measure to prevent infectious diseases in
      domestic animals. Development of novel vaccines demands extensive studies with
      new technologies, such as using novel adjuvants and immunomodulatory molecules.
      The co-stimulatory molecule 4-1BB provides a key signal that directs the fate of
      T cells during activation, and thus is important to their function in immune
      protection. To determine whether host immune responses to viral infection could
      be promoted by enhancing 4-1BB co-stimulation, in this study, we produced
      transgenic pig clones expressing an extra copy of the 4-1BB gene by clustered
      regularly interspaced short palindromic repeats/CRISPR-associated gene 9-mediated
      homologous recombination at the Rosa26 locus. The immune responses of transgenic
      pigs to porcine reproductive and respiratory syndrome virus (PRRSV) vaccine were
      determined on day 14. We show that peripheral blood lymphocytes of transgenic
      pigs expressed around twice the level of 4-1BB mRNA than those of control pigs.
      We also found IL-2, TNF-alpha, and granzyme B mRNA levels as well as PRRSV
      specific IFN-gamma response were significantly upregulated in 4-1BB transgenic
      pigs, leading to more efficient cytotoxic T lymphocyte (CTL) killing, whereas the
      expressions of IL-4, IL-17, and Foxp3 were not affected. These results indicate
      that higher levels of 4-1BB expression involve in promoting Th1 differentiation
      and enhancing specific CTL responses to PRRSV, and provide a novel approach to
      increase the efficacy of current vaccines to control the infectious diseases.

PMID- 29326719
TI  - Thyroid Autoantibodies Display both "Original Antigenic Sin" and Epitope
      Spreading.
AB  - Evidence for original antigenic sin in spontaneous thyroid autoimmunity is
      revealed by autoantibody interactions with immunodominant regions on thyroid
      autoantigens, thyroglobulin (Tg), thyroid peroxidase (TPO), and the thyrotropin
      receptor (TSHR) A-subunit. In contrast, antibodies induced by immunization of
      rabbits or mice recognize diverse epitopes. Recognition of immunodominant regions
      persists despite fluctuations in autoantibody levels following treatment or over
      time. The enhancement of spontaneously arising pathogenic TSHR antibodies in
      transgenic human thyrotropin receptor/NOD.H2h4 mice by injecting a non-pathogenic
      form of TSHR A-subunit protein also provides evidence for original antigenic sin.
      From other studies, antigen presentation by B cells, not dendritic cells, is
      likely responsible for original antigenic sin. Recognition of restricted epitopes
      on the large glycosylated thyroid autoantigens (60-kDa A-subunit, 100-kDa TPO,
      and 600-kDa Tg) facilitates exploring the amino acid locations in the
      immunodominant regions. Epitope spreading has also been revealed by
      autoantibodies in thyroid autoimmunity. In humans, and in mice that spontaneously
      develop autoimmunity to all three thyroid autoantigens, autoantibodies develop
      first to Tg and later to TPO and the TSHR A-subunit. The pattern of
      intermolecular epitope spreading is related in part to the thyroidal content of
      Tg, TPO and TSHR A-subunit and to the molecular sizes of these proteins.
      Importantly, the epitope spreading pattern provides a rationale for future
      antigen-specific manipulation to block the development of all thyroid
      autoantibodies by inducing tolerance to Tg, first in the autoantigen cascade.
      Because of its abundance, Tg may be the autoantigen of choice to explore antigen
      specific treatment, preventing the development of pathogenic TSHR antibodies.

PMID- 29326722
TI  - Regular Wounding in a Natural System: Bacteria Associated With Reproductive
      Organs of Bedbugs and Their Quorum Sensing Abilities.
AB  - During wounding, tissues are disrupted so that bacteria can easily enter the host
      and trigger a host response. Both the host response and bacterial communication
      can occur through quorum sensing (QS) and quorum sensing inhibition (QSI). Here,
      we characterize the effect of wounding on the host-associated bacterial community
      of the bed bug. This is a model system where the male is wounding the female
      during every mating. Whereas several aspects of the microbial involvement during
      wounding have been previously examined, it is not clear to what extent QS and QSI
      play a role. We find that the microbiome differs depending on mating and feeding
      status of female bedbugs and is specific to the location of isolation. Most
      organs of bedbugs harbor bacteria, which are capable of both QS and QSI
      signaling. By focusing on the prokaryotic quorum communication system, we provide
      a baseline for future research in this unique system. We advocate the bedbug
      system as suitable for studying the effects of bacteria on reproduction and for
      addressing prokaryote and eukaryote communication during wounding.

PMID- 29326721
TI  - Defenders and Challengers of Endothelial Barrier Function.
AB  - Regulated vascular permeability is an essential feature of normal physiology and
      its dysfunction is associated with major human diseases ranging from cancer to
      inflammation and ischemic heart diseases. Integrity of endothelial cells also
      play a prominent role in the outcome of surgical procedures and organ transplant.
      Endothelial barrier function and integrity are regulated by a plethora of highly
      specialized transmembrane receptors, including claudin family proteins, occludin,
      junctional adhesion molecules (JAMs), vascular endothelial (VE)-cadherin, and the
      newly identified immunoglobulin (Ig) and proline-rich receptor-1 (IGPR-1) through
      various distinct mechanisms and signaling. On the other hand, vascular
      endothelial growth factor (VEGF) and its tyrosine kinase receptor, VEGF receptor
      2, play a central role in the destabilization of endothelial barrier function.
      While claudins and occludin regulate cell-cell junction via recruitment of zonula
      occludens (ZO), cadherins via catenin proteins, and JAMs via ZO and afadin, IGPR
      1 recruits bullous pemphigoid antigen 1 [also called dystonin (DST) and SH3
      protein interacting with Nck90/WISH (SH3 protein interacting with Nck)].
      Endothelial barrier function is moderated by the function of transmembrane
      receptors and signaling events that act to defend or destabilize it. Here, I
      highlight recent advances that have provided new insights into endothelial
      barrier function and mechanisms involved. Further investigation of these
      mechanisms could lead to the discovery of novel therapeutic targets for human
      diseases associated with endothelial dysfunction.

PMID- 29326723
TI  - Value of the Overall Pneumococcal Polysaccharide Response in the Diagnosis of
      Primary Humoral Immunodeficiencies.
AB  - Background: An overall response assay [OVA, based on a 23-valent pneumococcal
      polysaccharide vaccine (PPV23)] is widely used to screen for anti-pneumococcal
      antibodies. Given the heterogeneity of response from one polysaccharide (PS) to
      another, a World Health Organization-standardized serotype-specific enzyme-linked
      immunosorbent assay (SSA) is considered to be the only reliable method for
      testing anti-PS antibody responses in individuals with suspected primary
      immunodeficiencies (PIDs). Objective: To evaluate the OVA relative to the
      reference SSA. Methods: Serum samples of adult patients referred for a suspected
      PID were collected before and then 4-8 weeks after immunization with PPV23. The
      anti-pneumococcal response was systematically assessed with an SSA (7-16
      serotypes) and interpreted according to the American Academy of Asthma, Allergy
      and Immunology's current guidelines. We used receiver operating characteristic
      curves and agreement indices to assess the OVA's diagnostic value in a first
      cohort. In order to validate these findings, a second (validation) cohort was
      then prospectively included. Results: Sixty-two adult patients were included, and
      42 (67.7%) were defined as poor responders according to the SSA. Only the post
      immunization titer in the OVA was able to correctly identify poor responders; a
      titer below 110 mg/L gave a positive predictive value of 100% [identifying 24
      (57.1%) of the 42 poor responders], and similar levels of diagnostic performance
      were observed in the validation cohort. The pre-vaccination antibody titer, the
      post/pre-vaccination antibody titer ratio and a post-vaccination titer above 110
      mg/L in the OVA were not predictive of the response in the SSA. Conclusion: A
      post-vaccination antibody titer below 110 mg/L in the OVA was constantly
      associated with a poor PPV23 response using the SSA. In all other cases, SSA is
      the only reliable method for assessing diagnostic vaccination with PPV23.

PMID- 29326724
TI  - beta2 Integrins As Regulators of Dendritic Cell, Monocyte, and Macrophage
      Function.
AB  - Emerging evidence suggests that the beta2 integrin family of adhesion molecules
      have an important role in suppressing immune activation and inflammation. beta2
      integrins are important adhesion and signaling molecules that are exclusively
      expressed on leukocytes. The four beta2 integrins (CD11a, CD11b, CD11c, and CD11d
      paired with the beta2 chain CD18) play important roles in regulating three key
      aspects of immune cell function: recruitment to sites of inflammation; cell-cell
      contact formation; and downstream effects on cellular signaling. Through these
      three processes, beta2 integrins both contribute to and regulate immune
      responses. This review explores the pro- and anti-inflammatory effects of beta2
      integrins in monocytes, macrophages, and dendritic cells and how they influence
      the outcome of immune responses. We furthermore discuss how imbalances in beta2
      integrin function can have far-reaching effects on mounting appropriate immune
      responses, potentially influencing the development and progression of autoimmune
      and inflammatory diseases. Therapeutic targeting of beta2 integrins, therefore,
      holds enormous potential in exploring treatment options for a variety of
      inflammatory conditions.

PMID- 29326725
TI  - Anti-inflammatory Effects of Heme Oxygenase-1 Depend on Adenosine A2A- and A2B
      Receptor Signaling in Acute Pulmonary Inflammation.
AB  - Acute pulmonary inflammation is still a frightening complication in intensive
      care units. In our previous study, we determined that heme oxygenase (HO)-1 had
      anti-inflammatory effects in pulmonary inflammation. Recent literature has
      emphasized a link between HO-1 and the nucleotide adenosine. Since adenosine A2A-
      and A2B-receptors play a pivotal role in pulmonary inflammation, we investigated
      their link to the enzyme HO-1. In a murine model of pulmonary inflammation, the
      activation of HO-1 by hemin significantly decreased polymorphonuclear leukocyte
      (PMN) migration into the lung. This anti-inflammatory reduction of PMN migration
      was abolished in A2A- and A2B-knockout mice. Administration of hemin
      significantly reduced chemokine levels in the BAL of wild-type animals but had no
      effects in A2A-/- and A2B-/- mice. Microvascular permeability was significantly
      attenuated in HO-1-stimulated wild-type mice, but not in A2A-/- and A2B-/- mice.
      The activity of HO-1 rose after LPS inhalation in wild-type animals and,
      surprisingly, also in A2A-/- and A2B-/- mice after the additional administration
      of hemin. Immunofluorescence images of animals revealed alveolar macrophages to
      be the major source of HO-1 activity in both knockout strains-in contrast to wild
      type animals, where HO-1 was also significantly augmented in the lung tissue. In
      vitro studies on PMN migration further confirmed our in vivo findings. In
      conclusion, we linked the anti-inflammatory effects of HO-1 to functional A2A/A2B
      receptor signaling under conditions of pulmonary inflammation. Our findings may
      explain why targeting HO-1 in acute pulmonary inflammation has failed to prove
      effective in some patients, since septic patients have altered adenosine receptor
      expression.

PMID- 29326726
TI  - Apoptotic Cell Clearance in Drosophila melanogaster.
AB  - The swift clearance of apoptotic cells (ACs) (efferocytosis) by phagocytes is a
      critical event during development of all multicellular organisms. It is achieved
      through phagocytosis by professional or amateur phagocytes. Failure in this
      process can lead to the development of inflammatory autoimmune or
      neurodegenerative diseases. AC clearance has been conserved throughout evolution,
      although many details in its mechanisms remain to be explored. It has been
      studied in the context of mammalian macrophages, and in the nematode
      Caenorhabditis elegans, which lacks "professional" phagocytes such as
      macrophages, but in which other cell types can engulf apoptotic corpses. In
      Drosophila melanogaster, ACs are engulfed by macrophages, glial, and epithelial
      cells. Drosophila macrophages perform similar functions to those of mammalian
      macrophages. They are professional phagocytes that participate in phagocytosis of
      ACs and pathogens. Study of AC clearance in Drosophila has identified some key
      elements, like the receptors Croquemort and Draper, promoting Drosophila as a
      suitable model to genetically dissect this process. In this review, we survey
      recent works of AC clearance pathways in Drosophila, and discuss the
      physiological outcomes and consequences of this process.

PMID- 29326727
TI  - Gut Microbiota Dysbiosis Drives and Implies Novel Therapeutic Strategies for
      Diabetes Mellitus and Related Metabolic Diseases.
AB  - Accumulating evidence over the past decade has linked the development of
      metabolic syndrome related to diabetes to variations in gut microbiota, an
      emerging, critical homeostatic regulator of host energy metabolism and immune
      responses. Mechanistic studies in rodent models have revealed an ever-increasing
      multitude of molecular mechanisms whereby the gut microbiota interacts with
      various host sensing and signaling pathways, leading to modulation of endocrine
      system, immune responses, nervous system activity, and hence, the predisposition
      to metabolic diseases. Remarkably, the microbiota-driven immune responses in
      metabolic tissues and the host nutrient-sensing mechanisms of gut microbial
      metabolites, in particular short-chain fatty acids, have been significantly
      associated with the proneness to diabetes and related disorders. This review will
      synthesize the recent efforts on unraveling the mediating role of gut microbiota
      in the pathogenesis of metabolic diseases, aiming to reveal new therapeutic
      opportunities.

PMID- 29326729
TI  - Mapping QTLs Controlling Flowering Time and Important Agronomic Traits in Pearl
      Millet.
AB  - Pearl millet [Pennisetum glaucum (L.) R. Br.] is a staple crop for the people of
      arid and semi-arid regions of the world. It is fast gaining importance as a
      climate resilient nutricereal. Exploiting the bold seeded, semi-dwarf, and early
      flowering genotypes in pearl millet is a key breeding strategy to enhance yield,
      adaptability, and for adequate food in resource-poor zones. Genetic variation for
      agronomic traits of pearl millet inbreds can be used to dissect complex traits
      through quantitative trait locus (QTL) mapping. This study was undertaken to map
      a set of agronomically important traits like flowering time (FT), plant height
      (PH), panicle length (PL), and grain weight (self and open-pollinated seeds) in
      the recombinant inbred line (RIL) population of ICMB 841-P3 * 863B-P2 cross.
      Excluding grain weight (open pollinated), heritabilities for FT, PH, PL, grain
      weight (selfed) were in high to medium range. A total of six QTLs for FT were
      detected on five chromosomes, 13 QTLs for PH on six chromosomes, 11 QTLs for PL
      on five chromosomes, and 14 QTLs for 1,000-grain weight (TGW) spanning five
      chromosomes. One major QTL on LG3 was common for FT and PH. Three major QTLs for
      PL, one each on LG1, LG2, and LG6B were detected. The large effect QTL for TGW
      (self) on LG6B had a phenotypic variance (R2) of 62.1%. The R2 for FT, TGW
      (self), and PL ranged from 22.3 to 59.4%. A total of 21 digenic interactions were
      discovered for FT (R2 = 18-40%) and PL (R2 = 13-19%). The epistatic effects did
      not reveal any significant QTL * QTL * environment (QQE) interactions. The mapped
      QTLs for flowering time and other agronomic traits in present experiment can be
      used for marker-assisted selection (MAS) and genomic selection (GS) breeding
      programs.

PMID- 29326728
TI  - Immunoglobulin G1 Allotype Influences Antibody Subclass Distribution in Response
      to HIV gp140 Vaccination.
AB  - Antibody subclasses exhibit extensive polymorphisms (allotypes) that could
      potentially impact the quality of HIV-vaccine induced B cell responses. Allotypes
      of immunoglobulin (Ig) G1, the most abundant serum antibody, have been shown to
      display altered functional properties in regard to serum half-life, Fc-receptor
      binding and FcRn-mediated mucosal transcytosis. To investigate the potential link
      between allotypic IgG1-variants and vaccine-generated humoral responses in a
      cohort of 14 HIV vaccine recipients, we developed a novel protocol for rapid IgG1
      allotyping. We combined PCR and ELISA assays in a dual approach to determine the
      IgG1 allotype identity (G1m3 and/or G1m1) of trial participants, using human
      plasma and RNA isolated from PBMC. The IgG1-allotype distribution of our
      participants mirrored previously reported results for caucasoid populations. We
      observed elevated levels of HIV gp140-specific IgG1 and decreased IgG2 levels
      associated with the G1m1-allele, in contrast to G1m3 carriers. These data suggest
      that vaccinees homozygous for G1m1 are predisposed to develop elevated Ag
      specific IgG1:IgG2 ratios compared to G1m3-carriers. This elevated IgG1:IgG2
      ratio was further associated with higher FcgammaR-dimer engagement, a surrogate
      for potential antibody-dependent cellular cytotoxicity (ADCC) and antibody
      dependent cellular phagocytosis (ADCP) function. Although preliminary, these
      results suggest that IgG1 allotype may have a significant impact on IgG subclass
      distribution in response to vaccination and associated Fc-mediated effector
      functions. These results have important implications for ongoing HIV vaccine
      efficacy studies predicated on engagement of FcgammaR-mediated cellular functions
      including ADCC and ADCP, and warrant further investigation. Our novel allotyping
      protocol provides new tools to determine the potential impact of IgG1 allotypes
      on vaccine efficacy.

PMID- 29326731
TI  - Mapping and Identifying a Candidate Gene (Bnmfs) for Female-Male Sterility
      through Whole-Genome Resequencing and RNA-Seq in Rapeseed (Brassica napus L.).
AB  - In oilseed crops, carpel and stamen development play vital roles in pollination
      and rapeseed yield, but the genetic mechanisms underlying carpel and stamen
      development remain unclear. Herein, a male- and female-sterile mutant was
      obtained in offspring of a (Brassica napus cv. Qingyou 14) * (Qingyou 14 * B.
      rapa landrace Dahuang) cross. Subsequently, F2-F9 populations were generated
      through selfing of the heterozygote plants among the progeny of each generation.
      The male- and female-sterility exhibited stable inheritance in successive
      generations and was controlled by a recessive gene. The mutant kept the same
      chromosome number (2n = 38) as B. napus parent but showed abnormal meiosis for
      male and female. One candidate gene for the sterility was identified by simple
      sequence repeat (SSR) and insertion deletion length polymorphism (InDel) markers
      in F7-F9 plants, and whole-genome resequencing with F8 pools and RNA sequencing
      with F9 pools. Whole-genome resequencing found three candidate intervals (35.40
      35.68, 35.74-35.75, and 45.34-46.45 Mb) on chromosome C3 in B. napus and
      candidate region for Bnmfs was narrowed to approximately 1.11-Mb (45.34-46.45 M)
      by combining SSR and InDel marker analyses with whole-genome resequencing. From
      transcriptome profiling in 0-2 mm buds, all of the genes in the candidate
      interval were detected, and only two genes with significant differences
      (BnaC03g56670D and BnaC03g56870D) were revealed. BnaC03g56870D was a candidate
      gene that shared homology with the CYP86C4 gene of Arabidopsis thaliana.
      Quantitative reverse transcription (qRT)-PCR analysis showed that Bnmfs primarily
      functioned in flower buds. Thus, sequencing and expression analyses provided
      evidence that BnaC03g56870D was the candidate gene for male and female sterility
      in the B. napus mutant.

PMID- 29326730
TI  - Cyclotide Evolution: Insights from the Analyses of Their Precursor Sequences,
      Structures and Distribution in Violets (Viola).
AB  - Cyclotides are a family of plant proteins that are characterized by a cyclic
      backbone and a knotted disulfide topology. Their cyclic cystine knot (CCK) motif
      makes them exceptionally resistant to thermal, chemical, and enzymatic
      degradation. By disrupting cell membranes, the cyclotides function as host
      defense peptides by exhibiting insecticidal, anthelmintic, antifouling, and
      molluscicidal activities. In this work, we provide the first insight into the
      evolution of this family of plant proteins by studying the Violaceae, in
      particular species of the genus Viola. We discovered 157 novel precursor
      sequences by the transcriptomic analysis of six Viola species: V. albida var.
      takahashii, V. mandshurica, V. orientalis, V. verecunda, V. acuminata, and V.
      canadensis. By combining these precursor sequences with the phylogenetic
      classification of Viola, we infer the distribution of cyclotides across 63% of
      the species in the genus (i.e., ~380 species). Using full precursor sequences
      from transcriptomes, we show an evolutionary link to the structural diversity of
      the cyclotides, and further classify the cyclotides by sequence signatures from
      the non-cyclotide domain. Also, transcriptomes were compared to cyclotide
      expression on a peptide level determined using liquid chromatography-mass
      spectrometry. Furthermore, the novel cyclotides discovered were associated with
      the emergence of new biological functions.

PMID- 29326733
TI  - iTRAQ-Based Comparative Proteomic Analysis of Seedling Leaves of Two Upland
      Cotton Genotypes Differing in Salt Tolerance.
AB  - Cotton yields are greatly reduced under high salinity stress conditions, although
      cotton is considered a moderately salt-tolerant crop. Understanding at the
      molecular level how cotton responds to salt stress will help in developing salt
      tolerant varieties. Here, we combined physiological analysis with isobaric tags
      for relative and absolute quantitation (iTRAQ)-based proteomics of seedling
      leaves of 2 genotypes differing in salinity tolerance to 200 mM (18.3 dS/m) NaCl
      stress. Salt stress produced significant stress symptoms in the sensitive
      genotype Nan Dan Ba Di Da Hua (N), including lower relative water and chlorophyll
      contents and higher relative electrolyte leakage and Na+/K+ ratio in leaf
      samples, compared with those in the tolerant genotype Earlistaple 7 (Z). A total
      of 58 differentially abundant salt-responsive proteins were identified. Asp-Glu
      Ala-Asp (DEAD)-box ATP-dependent RNA helicase 3 and protochlorophyllide reductase
      were markedly suppressed after salt treatment, whereas the phosphate-related
      differentially abundant proteins (DAPs) phosphoethanolamine N-methyltransferase 1
      and 14-3-3-like protein E were induced, and all these proteins may play
      significant roles in salt stress. Twenty-nine salt-responsive proteins were also
      genotype specific, and 62.1 and 27.6% of these were related to chloroplast and
      defense responses, respectively. Based on the Arabidopsis thaliana protein
      interaction database, orthologs of 25 proteins showed interactions in
      Arabidopsis, and among these, a calmodulin protein was predicted to have 212
      functional partners. In addition, the Golgi apparatus and calcium may be
      important for salt secretion in cotton. Through integrative proteome and
      transcriptome analysis, 16 DAPs were matched to differentially expressed genes
      and verified using qRT-PCR. On the basis of these findings, we proposed that some
      proteins related to chloroplast, ATP, ribosomal, and phosphate metabolism as well
      as to the Golgi apparatus and calcium may play key roles in the short-term salt
      stress response of cotton seedling leaves.

PMID- 29326732
TI  - Exogenous Glycine Nitrogen Enhances Accumulation of Glycosylated Flavonoids and
      Antioxidant Activity in Lettuce (Lactuca sativa L.).
AB  - Glycine, the simplest amino acid in nature and one of the most abundant free
      amino acids in soil, is regarded as a model nutrient in organic nitrogen studies.
      To date, many studies have focused on the uptake, metabolism and distribution of
      organic nitrogen in plants, but few have investigated the nutritional performance
      of plants supplied with organic nitrogen. Lettuce (Lactuca sativa L.), one of the
      most widely consumed leafy vegetables worldwide, is a significant source of
      antioxidants and bioactive compounds such as polyphenols, ascorbic acid and
      tocopherols. In this study, two lettuce cultivars, Shenxuan 1 and Lollo Rossa,
      were hydroponically cultured in media containing 4.5, 9, or 18 mM glycine or 9 mM
      nitrate (control) for 4 weeks, and the levels of health-promoting compounds and
      antioxidant activity of the lettuce leaf extracts were evaluated. Glycine
      significantly reduced fresh weight compared to control lettuce, while 9 mM
      glycine significantly increased fresh weight compared to 4.5 or 18 mM glycine.
      Compared to controls, glycine (18 mM for Shenxuan 1; 9 mM for Lollo Rossa)
      significantly increased the levels of most antioxidants (including total
      polyphenols, alpha-tocopherol) and antioxidant activity, suggesting appropriate
      glycine supply promotes antioxidant accumulation and activity. Glycine induced
      most glycosylated quercetin derivatives and luteolin derivatives detected and
      decreased some phenolic acids compared to nitrate treatment. This study indicates
      exogenous glycine supplementation could be used strategically to promote the
      accumulation of health-promoting compounds and antioxidant activity of
      hydroponically grown lettuce, which could potentially improve human nutrition.

PMID- 29326734
TI  - JUNGBRUNNEN1 Confers Drought Tolerance Downstream of the HD-Zip I Transcription
      Factor AtHB13.
AB  - Low water availability is the major environmental factor limiting growth and
      productivity of plants and crops and is therefore considered of high importance
      for agriculture affected by climate change. Identifying regulatory components
      controlling the response and tolerance to drought stress is thus of major
      importance. The NAC transcription factor (TF) JUNGBRUNNEN1 (JUB1) from
      Arabidopsis thaliana extends leaf longevity under non-stress growth conditions,
      lowers cellular hydrogen peroxide (H2O2) level, and enhances tolerance against
      heat stress and salinity. Here, we additionally find that JUB1 strongly increases
      tolerance to drought stress in Arabidopsis when expressed from both, a
      constitutive (CaMV 35S) and an abiotic stress-induced (RD29A) promoter. Employing
      a yeast one-hybrid screen we identified HD-Zip class I TF AtHB13 as an upstream
      regulator of JUB1. AtHB13 has previously been reported to act as a positive
      regulator of drought tolerance. AtHB13 and JUB1 thereby establish a joint drought
      stress control module.

PMID- 29326735
TI  - Discovery of Consistent QTLs of Wheat Spike-Related Traits under Nitrogen
      Treatment at Different Development Stages.
AB  - Spike-related traits such as spike length (Sl), fertile spikelet number (Fsn),
      sterile spikelet number (Ssn), grain number per spike (Gns), and thousand-kernel
      weight (Tkw) are important factors influencing wheat yield. However, reliably
      stable markers that can be used for molecular breeding in different environments
      have not yet been identified. In this study, a double haploid (DH) population was
      used for quantitative trait locus (QTL) mapping of five spike-related traits
      under four different nitrogen (N) supply dates in two locations and years.
      Seventy additive QTLs with phenotypic variation ranging from 4.12 to 34.74% and
      10 major epistatic QTLs were identified. Eight important chromosomal regions on
      five chromosomes (1B, 2B, 2D, 5D, and 6A) were found. Sixteen stable QTLs were
      detected for which N application had little effect. Among those stable QTLs,
      QSl.sdau-2D-1, and QSl.sdau-2D-2, with phenotypic variation explained (PVE) of
      10.4 and 24.2%, respectively, were flanked by markers Xwmc112 and Xcfd53 in the
      same order. The QTLs QSsn.sdau-2B-1, QFsn.sdau-2B-1, and QGns.sdau-2B, with PVE
      ranging from 4.37 to 28.43%, collocated in the Xwmc179-Xbarc373 marker interval.
      The consistent kernel wheat QTL (QTkw.sdau-6A) on the long arm of chromosome 6A,
      flanked by SSR markers Xbarc1055 and Xwmc553, showed PVE of 5.87-15.18%. Among
      these stable QTLs, the two flanking markers Xwmc112 and Xcfd53 have been
      validated using different varieties and populations for selecting Sl. Therefore,
      these results will be of great value for marker-assisted selection (MAS) in
      breeding programs and will accelerate the understanding of the genetic
      relationships among spike-related traits at the molecular level.

PMID- 29326736
TI  - Evolution of the Crop Rhizosphere: Impact of Domestication on Root Exudates in
      Tetraploid Wheat (Triticum turgidum L.).
AB  - Domestication has induced major genetic changes in crop plants to satisfy human
      needs and as a consequence of adaptation to agroecosystems. This adaptation might
      have affected root exudate composition, which can influence the interactions in
      the rhizosphere. Here, using two different soil types (sand, soil), we provide an
      original example of the impact of domestication and crop evolution on root
      exudate composition through metabolite profiling of root exudates for a panel of
      10 wheat genotypes that correspond to the key steps in domestication of
      tetraploid wheat (wild emmer, emmer, durum wheat). Our data show that soil type
      can dramatically affect the composition of root exudates in the rhizosphere.
      Moreover, the composition of the rhizosphere metabolites is associated with
      differences among the genotypes of the wheat domestication groups, as seen by the
      high heritability of some of the metabolites. Overall, we show that domestication
      and breeding have had major effects on root exudates in the rhizosphere, which
      suggests the adaptive nature of these changes.

PMID- 29326737
TI  - Over-Expression of Arabidopsis EDT1 Gene Confers Drought Tolerance in Alfalfa
      (Medicago sativa L.).
AB  - Alfalfa (Medicago sativa L.) is an important legume forage crop with great
      economic value. However, as the growth of alfalfa is seriously affected by an
      inadequate supply of water, drought is probably the major abiotic environmental
      factor that most severely affects alfalfa production worldwide. In an effort to
      enhance alfalfa drought tolerance, we transformed the Arabidopsis Enhanced
      Drought Tolerance 1 (AtEDT1) gene into alfalfa via Agrobacterium-mediated
      transformation. Compared with wild type plants, drought stress treatment resulted
      in higher survival rates and biomass, but reduced water loss rates in the
      transgenic plants. Furthermore, transgenic alfalfa plants had increased stomatal
      size, but reduced stomatal density, and these stomatal changes contributed
      greatly to reduced water loss from leaves. Importantly, transgenic alfalfa plants
      exhibited larger root systems with larger root lengths, root weight, and root
      diameters than wild type plants. The transgenic alfalfa plants had reduced
      membrane permeability and malondialdehyde content, but higher soluble sugar and
      proline content, higher superoxide dismutase activity, higher chlorophyll
      content, enhanced expression of drought-responsive genes, as compared with wild
      type plants. Notably, transgenic alfalfa plants grew better in a 2-year field
      trial and showed enhanced growth performance with increased biomass yield. All of
      our morphological, physiological, and molecular analyses demonstrated that the
      ectopic expression of AtEDT1 improved growth and enhanced drought tolerance in
      alfalfa. Our study provides alfalfa germplasm for use in forage improvement
      programs, and may help to increase alfalfa production in arid lands.

PMID- 29326738
TI  - Editorial: Evolution of Gene Regulatory Networks in Plant Development.

PMID- 29326739
TI  - Tomato Reproductive Success Is Equally Affected by Herbivores That Induce or That
      Suppress Defenses.
AB  - Herbivory induces plant defenses. These responses are often costly, yet enable
      plants under attack to reach a higher fitness than they would have reached
      without these defenses. Spider mites (Tetranychus ssp.) are polyphagous plant
      pests. While most strains of the species Tetranychus urticae induce defenses at
      the expense of their performance, the species Tetranychus evansi suppresses plant
      defenses and thereby maintains a high performance. Most data indicate that
      suppression is a mite-adaptive trait. Suppression is characterized by a massive
      down-regulation of plant gene-expression compared to plants infested with defense
      inducing mites as well as compared to control plants, albeit to a lesser extent.
      Therefore, we hypothesized that suppression may also benefit a plant since the
      resources saved during down-regulation could be used to increase reproduction. To
      test this hypothesis, we compared fruit and viable seed production of uninfested
      tomato plants with that of plants infested with defense-inducing or defense
      suppressing mites. Mite-infested plants produced fruits faster than control
      plants albeit in lower total amounts. The T. evansi-infested plants produced the
      lowest number of fruits. However, the number of viable seeds was equal across
      treatments at the end of the experiment. Nonetheless, at this stage control
      plants were still alive and productive and therefore reach a higher lifetime
      fitness than mite-infested plants. Our results indicate that plants have plastic
      control over reproduction and can speed up fruit- and seed production when
      conditions are unfavorable. Moreover, we showed that although suppressed plants
      are less productive in terms of fruit production than induced plants, their
      lifetime fitness was equal under laboratory conditions. However, under natural
      conditions the fitness of plants such as tomato will also depend on the
      efficiency of seed dispersal by animals. Hence, we argue that the fitness of
      induced plants in the field may be promoted more by their higher fruit production
      relative to that of their suppressed counterparts.

PMID- 29326740
TI  - Engineered Dwarf Male-Sterile Rice: A Promising Genetic Tool for Facilitating
      Recurrent Selection in Rice.
AB  - Rice is a crop feeding half of the world's population. With the continuous raise
      of yield potential via genetic improvement, rice breeding has entered an era
      where multiple genes conferring complex traits must be efficiently manipulated to
      increase rice yield further. Recurrent selection is a sound strategy for
      manipulating multiple genes and it has been successfully performed in allogamous
      crops. However, the difficulties in emasculation and hand pollination had
      obstructed efficient use of recurrent selection in autogamous rice. Here, we
      report development of the dwarf male-sterile rice that can facilitate recurrent
      selection in rice breeding. We adopted RNAi technology to synergistically
      regulate rice plant height and male fertility to create the dwarf male-sterile
      rice. The RNAi construct pTCK-EGGE, targeting the OsGA20ox2 and OsEAT1 genes, was
      constructed and used to transform rice via Agrobacterium-mediated transformation.
      The transgenic T0 plants showing largely reduced plant height and complete male
      sterile phenotypes were designated as the dwarf male-sterile plants. Progenies of
      the dwarf male-sterile plants were obtained by pollinating them with pollens from
      the wild-type. In the T1 and T2 populations, half of the plants were still dwarf
      male-sterile; the other half displayed normal plant height and male fertility
      which were designated as tall and male-fertile plants. The tall and male-fertile
      plants are transgene-free and can be self-pollinated to generate new varieties.
      Since emasculation and hand pollination for dwarf male-sterile rice plants is no
      longer needed, the dwarf male-sterile rice can be used to perform recurrent
      selection in rice. A dwarf male-sterile rice-based recurrent selection model has
      been proposed.

PMID- 29326742
TI  - Perception of Salicylic Acid in Physcomitrella patens.
AB  - Salicylic acid (SA) is a key signaling molecule in plant immunity. Two types of
      SA receptors, NPR1 and NPR3/NPR4, were reported to be involved in the perception
      of SA in Arabidopsis. SA is also synthesized in the non-vascular moss
      Physcomitrella patens following pathogen infection. Sequence analysis revealed
      that there is only one NPR1/NPR3/NPR4-like protein in P. patens. This agrees with
      the phylogenetic study that showed the divergence of NPR1 and NPR3/NPR4 from the
      same ancestor during the evolution of higher plants. Intriguingly, expression of
      the P. patens NPR1/NPR3/NPR4-like gene in Arabidopsis does not complement the
      constitutive defense phenotype of the npr3 npr4 double mutant, but can partially
      rescue the mutant phenotypes of npr1-1, suggesting that it functions as an NPR1
      like positive regulator of SA-mediated immunity and P. patens does not have an SA
      receptor functioning similarly as NPR3/NPR4. Future characterization of the P.
      patens NPR1-like protein and analysis of its functions through knockout and
      biochemical approaches will help us better understand how SA is perceived and
      what its functions are in P. patens.

PMID- 29326741
TI  - Two Lysin-Motif Receptor Kinases, Gh-LYK1 and Gh-LYK2, Contribute to Resistance
      against Verticillium wilt in Upland Cotton.
AB  - Lysin-motif (LysM) receptor kinases (LYKs) play essential roles in recognition of
      chitin and activation of defense responses against pathogenic fungi in the model
      plants Arabidopsis and rice. The function of LYKs in non-model plants, however,
      remains elusive. In the present work, we found that the transcription of two LYK
      encoding genes from cotton, Gh-LYK1 and Gh-LYK2, was induced after Verticillium
      dahliae infection. Virus-induced gene silencing (VIGS) of Gh-LYK1 and Gh-LYK2 in
      cotton plants compromises resistance to V. dahliae. As putative pattern
      recognition receptors (PRRs), both Gh-LYK1 and Gh-LYK2 are membrane-localized,
      and all three LysM domains of Gh-LYK1 and Gh-LYK2 are required for their chitin
      binding ability. However, since Gh-LYK2, but not Gh-LYK1, is a pseudo-kinase and,
      on the other hand, the ectodomain (ED) of Gh-LYK2 can induce reactive oxygen
      species (ROS) burst in planta, Gh-LYK2 and Gh-LYK1 may contribute differently to
      cotton defense. Taken together, our results establish that both Gh-LYK1 and Gh
      LYK12 are required for defense against V. dahliae in cotton, possibly through
      different mechanisms.

PMID- 29326744
TI  - Physiological Plasticity Is Important for Maintaining Sugarcane Growth under
      Water Deficit.
AB  - The water availability at early phenological stages is critical for crop
      establishment and sugarcane varieties show differential performance under
      drought. Herein, we evaluated the relative importance of morphological and
      physiological plasticity of young sugarcane plants grown under water deficit,
      testing the hypothesis that high phenotypic plasticity is associated with drought
      tolerance. IACSP95-5000 is a high yielding genotype and IACSP94-2094 has good
      performance under water limiting environments. Plants were grown in rhizotrons
      for 35 days under three water availabilities: high (soil water matric potential
      [Psim] higher than -20 kPa); intermediate (Psim reached -65 and -90 kPa at the
      end of experimental period) and low (Psim reached values lower than -150 kPa).
      Our data revealed that morphological and physiological responses of sugarcane to
      drought are dependent on genotype and intensity of water deficit. In general,
      IACSP95-5000 showed higher physiological plasticity given by leaf gas exchange
      and photochemical traits, whereas IACSP94-2094 showed higher morphological
      plasticity determined by changes in leaf area (LA) and specific LA. As IACSP94
      2094 accumulated less biomass than IACSP95-5000 under varying water availability,
      it is suggested that high morphological plasticity does not always represent an
      effective advantage to maintain plant growth under water deficit. In addition,
      our results revealed that sugarcane varieties face water deficit using distinct
      strategies based on physiological or morphological changes. When the
      effectiveness of those changes in maintaining plant growth under low water
      availability is taken into account, our results indicate that the physiological
      plasticity is more important than the morphological one in young sugarcane
      plants.

PMID- 29326743
TI  - Plant Responses to Abiotic Stress Regulated by Histone Deacetylases.
AB  - In eukaryotic cells, histone acetylation and deacetylation play an important role
      in the regulation of gene expression. Histone acetylation levels are modulated by
      histone acetyltransferases and histone deacetylases (HDACs). Recent studies
      indicate that HDACs play essential roles in the regulation of gene expression in
      plant response to environmental stress. In this review, we discussed the recent
      advance regarding the plant HDACs and their functions in the regulation of
      abiotic stress responses. The role of HDACs in autophagy was also discussed.

PMID- 29326746
TI  - Stoichiometric Correlation Analysis: Principles of Metabolic Functionality from
      Metabolomics Data.
AB  - Recent advances in metabolomics technologies have resulted in high-quality (time
      resolved) metabolic profiles with an increasing coverage of metabolic pathways.
      These data profiles represent read-outs from often non-linear dynamics of
      metabolic networks. Yet, metabolic profiles have largely been explored with
      regression-based approaches that only capture linear relationships, rendering it
      difficult to determine the extent to which the data reflect the underlying
      reaction rates and their couplings. Here we propose an approach termed
      Stoichiometric Correlation Analysis (SCA) based on correlation between positive
      linear combinations of log-transformed metabolic profiles. The log-transformation
      is due to the evidence that metabolic networks can be modeled by mass action law
      and kinetics derived from it. Unlike the existing approaches which establish a
      relation between pairs of metabolites, SCA facilitates the discovery of higher
      order dependence between more than two metabolites. By using a paradigmatic model
      of the tricarboxylic acid cycle we show that the higher-order dependence reflects
      the coupling of concentration of reactant complexes, capturing the subtle
      difference between the employed enzyme kinetics. Using time-resolved metabolic
      profiles from Arabidopsis thaliana and Escherichia coli, we show that SCA can be
      used to quantify the difference in coupling of reactant complexes, and hence,
      reaction rates, underlying the stringent response in these model organisms. By
      using SCA with data from natural variation of wild and domesticated wheat and
      tomato accession, we demonstrate that the domestication is accompanied by loss of
      such couplings, in these species. Therefore, application of SCA to metabolomics
      data from natural variation in wild and domesticated populations provides a
      mechanistic way to understanding domestication and its relation to metabolic
      networks.

PMID- 29326747
TI  - Deletion of CGLD1 Impairs PSII and Increases Singlet Oxygen Tolerance of Green
      Alga Chlamydomonas reinhardtii.
AB  - The green alga Chlamydomonas reinhardtii is a key model organism for studying
      photosynthesis and oxidative stress in unicellular eukaryotes. Using a forward
      genetics approach, we have identified and characterized a mutant x32, which lacks
      a predicted protein named CGLD1 (Conserved in Green Lineage and Diatom 1) in
      GreenCut2, under normal and stress conditions. We show that loss of CGLD1
      resulted in minimal photoautotrophic growth and PSII activity in the organism. We
      observed reduced amount of PSII complex and core subunits in the x32 mutant based
      on blue-native (BN)/PAGE and immunoblot analysis. Moreover, x32 exhibited
      increased sensitivity to high-light stress and altered tolerance to different
      reactive oxygenic species (ROS) stress treatments, i.e., decreased resistance to
      H2O2/or tert-Butyl hydroperoxide (t-BOOH) and increased tolerance to neutral red
      (NR) and rose bengal (RB) that induce the formation of singlet oxygen,
      respectively. Further analysis via quantitative real-time PCR (qRT-PCR) indicated
      that the increased singlet-oxygen tolerance of x32 was largely correlated with up
      regulated gene expression of glutathione-S-transferases (GST). The phenotypical
      and physiological implications revealed from our experiments highlight the
      important roles of CGLD1 in maintaining structure and function of PSII as well as
      in protection of Chlamydomonas under photo-oxidative stress conditions.

PMID- 29326745
TI  - Brassinosteroids: A Promising Option in Deciphering Remedial Strategies for
      Abiotic Stress Tolerance in Rice.
AB  - Rice is an important staple crop as it feeds about a half of the earth's
      population. It is known to be sensitive to a range of abiotic stresses which
      result in significant decline in crop productivity. Recently, the use of
      phytohormones for abiotic stress amelioration has generated considerable
      interest. Plants adapt to various environmental stresses by undergoing series of
      changes at physiological and molecular levels which are cooperatively modulated
      by various phytohormones. Brassinosteroids (BRs) are a class of naturally
      occurring steroidal phytohormones, best known for their role in plant growth and
      development. For the past two decades, greater emphasis on studies related to BRs
      biosynthesis, distribution and signaling has resulted in better understanding of
      BRs function. Recent advances in the use of contemporary genetic, biochemical and
      proteomic tools, with a vast array of accessible biological resources has led to
      an extensive exploration of the key regulatory components in BR signaling
      networks, thus making it one of the most well-studied hormonal pathways in
      plants. The present review highlights the advancements of knowledge in BR
      research and links it with its growing potential in abiotic stress management for
      important crop like rice.

PMID- 29326749
TI  - Introgression of the Aegilops speltoides Su1-Ph1 Suppressor into Wheat.
AB  - Meiotic pairing between homoeologous chromosomes in polyploid wheat is inhibited
      by the Ph1 locus on the long arm of chromosome 5 in the B genome. Aegilops
      speltoides (genomes SS), the closest relative of the progenitor of the wheat B
      genome, is polymorphic for genetic suppression of Ph1. Using this polymorphism,
      two major suppressor loci, Su1-Ph1 and Su2-Ph1, have been mapped in Ae.
      speltoides. Su1-Ph1 is located in the distal, high-recombination region of the
      long arm of the Ae. speltoides chromosome 3S. Its location and tight linkage to
      marker Xpsr1205-3S makes Su1-Ph1 a suitable target for introgression into wheat.
      Here, Xpsr1205-3S was introgressed into hexaploid bread wheat cv. Chinese Spring
      (CS) and from there into tetraploid durum wheat cv. Langdon (LDN). Sequential
      fluorescence in situ hybridization and genomic in situ hybridization showed that
      an Ae. speltoides segment with Xpsr1205-3S replaced the distal end of the long
      arm of chromosome 3A. In the CS genetic background, the chromosome induced
      homoeologous chromosome pairing in interspecific hybrids with Ae. peregrina but
      not in progenies from crosses involving alien disomic substitution lines. In the
      LDN genetic background, the chromosome induced homoeologous chromosome pairing in
      both interspecific hybrids and progenies from crosses involving alien disomic
      substitution lines. We conclude that the recombined chromosome harbors Su1-Ph1
      but its expression requires expression of complementary gene that is present in
      LDN but absent in CS. We suggest that it is unlikely that Su1-Ph1 and ZIP4-1, a
      paralog of Ph1 located on wheat chromosomes 3A and 3B and Ae. tauschii chromosome
      3D, are equivalent. The utility of Su1-Ph1 for induction of recombination between
      homoeologous chromosomes in wheat is illustrated.

PMID- 29326748
TI  - Pseudomonas syringae pv. actinidiae Type III Effectors Localized at Multiple
      Cellular Compartments Activate or Suppress Innate Immune Responses in Nicotiana
      benthamiana.
AB  - Bacterial phytopathogen type III secreted (T3S) effectors have been strongly
      implicated in altering the interaction of pathogens with host plants. Therefore,
      it is useful to characterize the whole effector repertoire of a pathogen to
      understand the interplay of effectors in plants. Pseudomonas syringae pv.
      actinidiae is a causal agent of kiwifruit canker disease. In this study, we
      generated an Agrobacterium-mediated transient expression library of YFP-tagged
      T3S effectors from two strains of Psa, Psa-NZ V13 and Psa-NZ LV5, in order to
      gain insight into their mode of action in Nicotiana tabacum and N. benthamiana.
      Determining the subcellular localization of effectors gives an indication of the
      possible host targets of effectors. A confocal microscopy assay detecting YFP
      tagged Psa effectors revealed that the nucleus, cytoplasm and cell periphery are
      major targets of Psa effectors. Agrobacterium-mediated transient expression of
      multiple Psa effectors induced HR-like cell death (HCD) in Nicotiana spp.,
      suggesting that multiple Psa effectors may be recognized by Nicotiana spp.. Virus
      induced gene silencing (VIGS) of several known plant immune regulators, EDS1,
      NDR1, or SGT1 specified the requirement of SGT1 in HCD induced by several Psa
      effectors in N. benthamiana. In addition, the suppression activity of Psa
      effectors on HCD-inducing proteins and PTI was assessed. Psa effectors showed
      differential suppression activities on each HCD inducer or PTI. Taken together,
      our Psa effector repertoire analysis highlights the great diversity of T3S
      effector functions in planta.

PMID- 29326750
TI  - Integrative View of the Diversity and Evolution of SWEET and SemiSWEET Sugar
      Transporters.
AB  - Sugars Will Eventually be Exported Transporter (SWEET) and SemiSWEET are recently
      characterized families of sugar transporters in eukaryotes and prokaryotes,
      respectively. SemiSWEETs contain 3 transmembrane helices (TMHs), while SWEETs
      contain 7. Here, we performed sequence-based comprehensive analyses for SWEETs
      and SemiSWEETs across the biosphere. In total, 3,249 proteins were identified and
      ~60% proteins were found in green plants and Oomycota, which include a number of
      important plant pathogens. Protein sequence similarity networks indicate that
      proteins from different organisms are significantly clustered. Of note,
      SemiSWEETs with 3 or 4 TMHs that may fuse to SWEET were identified in plant
      genomes. 7-TMH SWEETs were found in bacteria, implying that SemiSWEET can be
      fused directly in prokaryote. 15-TMH extraSWEET and 25-TMH superSWEET were also
      observed in wild rice and oomycetes, respectively. The transporters can be
      classified into 4, 2, 2, and 2 clades in plants, Metazoa, unicellular eukaryotes,
      and prokaryotes, respectively. The consensus and coevolution of amino acids in
      SWEETs were identified by multiple sequence alignments. The functions of the
      highly conserved residues were analyzed by molecular dynamics analysis. The 19
      most highly conserved residues in the SWEETs were further confirmed by point
      mutagenesis using SWEET1 from Arabidopsis thaliana. The results proved that the
      conserved residues located in the extrafacial gate (Y57, G58, G131, and P191),
      the substrate binding pocket (N73, N192, and W176), and the intrafacial gate
      (P43, Y83, F87, P145, M161, P162, and Q202) play important roles for substrate
      recognition and transport processes. Taken together, our analyses provide a
      foundation for understanding the diversity, classification, and evolution of
      SWEETs and SemiSWEETs using large-scale sequence analysis and further show that
      gene duplication and gene fusion are important factors driving the evolution of
      SWEETs.

PMID- 29326751
TI  - The Role for the Small Cryptic Plasmids As Moldable Vectors for Genetic
      Innovation in Aeromonas salmonicida subsp. salmonicida.
AB  - In Aeromonas salmonicida subsp. salmonicida, a bacterium that causes fish
      disease, there are two types of small plasmids (<15 kbp): plasmids without known
      function, called cryptic plasmids, and plasmids that bear beneficial genes for
      the bacterium. Four among them are frequently detected in strains of A.
      salmonicida subsp. salmonicida: pAsa1, pAsa2, pAsa3, and pAsal1. The latter
      harbors a gene which codes for an effector of the type three secretion system,
      while the three others are cryptic. It is currently unclear why these cryptic
      plasmids are so highly conserved throughout strains of A. salmonicida subsp.
      salmonicida. In this study, three small plasmids, named pAsa10, pAsaXI and
      pAsaXII, are described. Linked to tetracycline resistance, a partial Tn1721
      occupies half of pAsa10. A whole Tn1721 is also present in pAsa8, another plasmid
      previously described in A. salmonicida subsp. salmonicida. The backbone of pAsa10
      has no relation with other plasmids described in this bacterium. However, the
      pAsaXI and pAsaXII plasmids are derivatives of cryptic plasmids pAsa3 and pAsa2,
      respectively. pAsaXI is identical to pAsa3, but bears a transposon with a gene
      that encodes for a putative virulence factor. pAsaXII, also found in Aeromonas
      bivalvium, has a 95% nucleotide identity with the backbone of pAsa2. Like pAsa7,
      another pAsa2-like plasmid recently described, orf2 and orf3 are missing and are
      replaced in pAsaXII by genes that encode a formaldehyde detoxification system.
      These new observations suggest that transposons and particularly Tn1721 are
      frequent and diversified in A. salmonicida subsp. salmonicida. Moreover, the
      discovery of pAsaXI and pAsaXII expands the group of small plasmids that are
      derived from cryptic plasmids and have a function. Although their precise roles
      remain to be determined, the present study shows that cryptic plasmids could
      serve as moldable vectors to acquire mobile elements such as transposons.
      Consequently, they could act as key agents of the diversification of virulence
      and adaptive traits of Aeromonas salmonicida subsp. salmonicida.

PMID- 29326754
TI  - Climate-Induced Landslides within the Larch Dominant Permafrost Zone of Central
      Siberia.
AB  - Climate impact on landslide occurrence and spatial patterns were analyzed within
      the larch-dominant communities associated with continuous permafrost areas of
      Central Siberia. We used high resolution satellite imagery (i.e. QuickBird,
      WorldView) to identify landslide scars over an area of 62000 km2. Landslide
      occurrence was analyzed with respect to climate variables (air temperature,
      precipitation, drought index SPEI), and GRACE satellite derived equivalent of
      water thickness anomalies (EWTA). Landslides were found only on southward facing
      slopes, and the occurrence of landslides increased exponentially with increasing
      slope steepness. Lengths of landslides correlated positively with slope
      steepness. The observed upper elevation limit of landslides tended to coincide
      with the tree line. Observations revealed landslides occurrence was also found to
      be strongly correlated with August precipitation (r = 0.81) and drought index (r
      = 0.7), with June-July-August soil water anomalies (i.e., EWTA, r = 0.68-0.7),
      and number of thawing days (i.e., a number of days with tmax > 0 degrees C; r =
      0.67). A significant increase in the variance of soil water anomalies was
      observed, indicating that occurrence of landslides may increase even with a
      stable mean precipitation level. The key-findings of this study are (1)
      landslides occurrence increased within the permafrost zone of Central Siberia in
      the beginning of the 21st century; (2) the main cause of increased landslides
      occurrence are extremes in precipitation and soil water anomalies; and (3)
      landslides occurrence are strongly dependent on relief features such as southward
      facing steep slopes.

PMID- 29326753
TI  - A Novel Role for CSRP1 in a Lebanese Family with Congenital Cardiac Defects.
AB  - Despite an obvious role for consanguinity in congenital heart disease (CHD), most
      studies fail to document a monogenic model of inheritance except for few cases.
      We hereby describe a first-degree cousins consanguineous Lebanese family with 7
      conceived children: 2 died in utero of unknown causes, 3 have CHD, and 4 have
      polydactyly. The aim of the study is to unveil the genetic variant(s) causing
      these phenotypes using next generation sequencing (NGS) technology. Targeted
      exome sequencing identified a heterozygous duplication in CSRP1 which leads to a
      potential frameshift mutation at position 154 of the protein. This mutation is
      inherited from the father, and segregates only with the CHD phenotype. The in
      vitro characterization demonstrates that the mutation dramatically abrogates its
      transcriptional activity over cardiac promoters like NPPA. In addition, it
      differentially inhibits the physical association of CSRP1 with SRF, GATA4, and
      with the newly described partner herein TBX5. Whole exome sequencing failed to
      show any potential variant linked to polydactyly, but revealed a novel missense
      mutation in TRPS1. This mutation is inherited from the healthy mother, and
      segregating only with the cardiac phenotype. Both TRPS1 and CSRP1 physically
      interact, and the mutations in each abrogate their partnership. Our findings add
      fundamental knowledge into the molecular basis of CHD, and propose the di-genic
      model of inheritance as responsible for such malformations.

PMID- 29326752
TI  - The Dynamics of microRNA Transcriptome in Bovine Corpus Luteum during Its
      Formation, Function, and Regression.
AB  - The formation, function, and subsequent regression of the ovarian corpus luteum
      (CL) are dynamic processes that enable ovary cyclical activity. Studies in whole
      ovary tissue have found microRNAs (miRNAs) to by critical for ovary function.
      However, relatively little is known about the role of miRNAs in the bovine CL.
      Utilizing small RNA next-generation sequencing we profiled miRNA transcriptome in
      bovine CL during the entire physiological estrous cycle, by sampling the CL on
      days: d 1-2, d 3-4, and d 5-7 (early CL, eCL), d 8-12 (mid CL, mCL), d 13-16
      (late CL, lCL), and d > 18 (regressed CL, rCL). We characterized patterns of
      miRNAs abundance and identified 42 miRNAs that were consistent significantly
      different expressed (DE) in the eCL relative to their expression at each of the
      analyzed stages (mCL, lCL, and rCL). Out of these, bta-miR-210-3p, -2898, -96, -7
      5p, -183-5p, -182, and -202 showed drastic up-regulation with a fold-change of
      >=2.0 and adjusted P < 0.01 in the eCL, while bta-miR-146a was downregulated at
      lCL and rCL vs. the eCL. Another 24, 11, and 21 miRNAs were significantly DE only
      between individual comparisons, eCL vs. the mCL, lCL, and rCL, respectively.
      Irrespective of cycle stage two miRNAs, bta-miR-21-5p and bta-miR-143 were
      identified as the most abundant miRNAs species and show opposing expression
      abundance. Whilst bta-miR-21-5p peaked in number of reads in the eCL and was
      significantly downregulated in the mCL and lCL, bta-miR-143 reached its peak in
      the rCL and is significantly downregulated in the eCL. MiRNAs with significant DE
      in at least one cycle stage (CL class) were further grouped into eight distinct
      clusters by the self-organizing tree algorithm (SOTA). Half of the clusters
      contain miRNAs with low-expression, whilst the other half contain miRNAs with
      high-expression levels during eCL. Prediction analysis for significantly DE
      miRNAs resulted in target genes involved with CL formation, functionalization and
      CL regression. This study is the most comprehensive profiling of miRNA
      transcriptome in bovine CL covering the entire estrous cycle and provides a
      compact database for further functional validation and biomarker identification
      relevant for CL viability and fertility.

PMID- 29326755
TI  - Effects of Noncovalent Interactions on the Catalytic Activity of Unsupported
      Colloidal Palladium Nanoparticles Stabilized with Thiolate Ligands.
AB  - This article presents the systematic evaluation of colloidal palladium
      nanoparticles functionalized with well-defined small organic ligands that provide
      spatial control of the geometric and electronic surface properties of
      nanoparticle catalysts. Palladium nanoparticles stabilized with thiolate ligands
      of different structures and functionalities (linear alkyl vs cyclohexyl vs
      phenyl) are synthesized using the thiosulfate protocol in a two-phase system. The
      structure and composition of palladium nanoparticles are characterized using
      transmission electron microscopy, thermogravimetric analysis, NMR, and UV-vis
      spectroscopies. The catalysis studies show that the chemical and structural
      compositions of monolayers surrounding the nanoparticle core greatly influence
      the overall activity and selectivity of colloidal palladium nanoparticle
      catalysts for the hydrogenation, isomerization, and hydrogenolysis of allylic
      alcohols. Especially, noncovalent interactions between surface phenyl ligands and
      incoming aromatic substrates are found to have a profound influence on the
      selectivity of colloidal palladium nanoparticles.

PMID- 29326756
TI  - Mismatch Between Homeless Families and the Homelessness Service System.
AB  - The enrollment phase of the Family Options Study provides information about the
      mismatch of the homeless service system and the needs and desires of families
      experiencing homelessness in 12 communities. One-fourth (25.8 percent) of the
      2,490 families screened for the study after shelter stays of a week were deemed
      ineligible for one or more of the interventions at initial screening, with
      ineligibility highest for those screened for transitional housing programs (28.9
      percent) and lower for short- and long-term rental subsidies (9.2 and 4.1
      percent). Families given priority offers of housing and service interventions for
      which they appeared eligible faced additional screening by programs and made
      decisions about whether to enroll. Considering all stages of this process,
      families were least likely to be eligible for and subsequently choose to enroll
      (within 9 months) in transitional housing programs (32.5 percent of those
      initially screened) and most likely to be eligible for and subsequently lease up
      with long-term subsidies (73.4 percent) with short-term subsidies in between
      (51.0 percent). Homeless system interventions systematically screen out families
      with housing and employment barriers, despite the presumption that these families
      are the families who need interventions in order to achieve housing and economic
      stability.

PMID- 29326757
TI  - Risk Models for Returns to Housing Instability Among Families Experiencing
      Homelessness.
AB  - This study developed risk models for returns to housing instability (that is,
      homelessness and unstable doubling-up situations) among families exiting
      emergency shelter. Participants included 446 families randomly assigned to
      receive priority offers of long-term housing subsidies and 578 families randomly
      assigned to usual care in the Family Options Study, a multisite experiment
      designed to test the impact of various housing and service interventions for
      homeless families. Relationships between family features recorded at shelter
      entry and returns to housing instability 20 months later were examined
      empirically. Correlation, hierarchical logistic regression, and receiver
      operating characteristic curves were used to combine family features into
      predictive risk models. Results indicated that few observable family features
      beyond previous housing instability offered predictive utility. Access to long
      term housing subsidies appears to reduce housing instability. Further research
      should examine whether disability benefits, reliable employment, or effective
      substance dependence treatment reduce housing instability.

PMID- 29326758
TI  - Families' Experiences of Doubling Up After Homelessness.
AB  - This study examined experiences of doubling up among families after episodes of
      homelessness. Doubling up refers to two or more adults or families residing in
      the same housing unit, which has been an increasing trend in the United States in
      recent decades. Within the past 14 years, the number of households containing
      more than one family, related or unrelated, has more than tripled. Although
      doubling up is increasingly common among families at all income levels, this
      study seeks to understand the experiences of doubling up among families who have
      been homeless. Through qualitative interviews with caregivers of 29 families, we
      analyzed advantages and disadvantages of doubling up with the caregiver's parent,
      other family, and nonfamily. Experiences were rated on a four-point scale-(1)
      mostly negative, (2) negative mixed, (3) positive mixed, and (4) mostly positive
      and coded for various positive and negative themes. Overall, we found that
      doubling up was a generally negative experience for families in our sample,
      regardless of their relationship to their hosts. Common themes included negative
      effects on children, undesirable environments, interpersonal tension, and
      feelings of impermanence and instability. For formerly sheltered families in this
      study, doubling up after shelter did not resolve their period of housing
      instability and may be only another stop in an ongoing cycle of homelessness.

PMID- 29326760
TI  - Both-Bone Forearm Fractures in Children with Minimum Four Years of Growth
      Remaining: Can Cast Achieve a Good Outcome at Skeletal Maturity?
AB  - Introduction: Both-bone forearm fractures in children can be treated non
      operatively with a cast. Most previous studies have shown favourable outcome;
      however, information on the functional outcome after skeletal maturity is still
      scanty. Therefore, this study was conducted to determine the functional outcome
      after skeletal maturity in fractures with at least four years of growth
      remaining. Materials and Methods: This retrospective study was conducted from
      March 2012 until March 2013. Age at the time of fracture was taken as until 10
      years for females and until 12 years old for males with at least four years of
      growth remaining. Fractures occurring in the diaphysis were included in the
      study. Functional outcomes were assessed at or after skeletal maturity. Results:
      Forty-four children fulfilled the criteria. The ages of the youngest and the
      oldest at the time of fracture was five and 12 years old respectively. Follow-up
      of the male and female patients were 7.4 years and 5.5 years respectively. There
      was a significant difference between post-reduction angulation and angulation at
      skeletal maturity of the radius and ulna (p<0.001). Out of 44 patients, 39 had
      excellent and five had good functional outcomes. No patient had fair or poor
      functional outcome. There was no association between the functional outcome and
      the angulation of forearm bones after skeletal maturity. Age at the time of
      fracture had a significant association with the functional outcome. Conclusion:
      Non-operative treatment of both-bone diaphyseal forearm fractures in a cast has
      good to excellent functional outcomes in children who still have four years of
      growth remaining.

PMID- 29326761
TI  - Prevalence Rate of Adolescent Idiopathic Scoliosis: Results of School-based
      Screening in Surabaya, Indonesia.
AB  - Introduction: Scoliosis is a lateral spinal deformity of 10 degrees or more,
      resulting in a C-shaped or S-shaped curve of the spine. Information about
      adolescent idiopathic scoliosis (AIS) prevalence rate is important not only for
      paediatric health care planning strategy but also for parent's awareness. This
      study aims to find the suitable inclination cut-off angle and the prevalence rate
      of AIS in Surabaya, Indonesia. Materials and Methods: This is a descriptive cross
      sectional study conducted in 2010. We performed stratified random sampling of 784
      Elementary and Junior High School students in Surabaya between 9-16 years of age.
      Scoliosis screening was performed by the Adam's forward bending test (FBT). The
      students with positive FBT were measured for the inclination angle with
      scoliometer, and then subjected to radiologic examination. Prevalence rate,
      gender ratio, and the cut-off point value of inclination angle were determined by
      a descriptive statistics analysis. Results: Adam's forward bending test was
      positive in 50 students (6,37%). Among them, 23 students (2,93%) four males and
      19 females had Cobb angle of >=10 degrees . The 5 degrees  cutoff point value of
      inclination angle had a 95.6% sensitivity, an 18.5% specificity, a 50% positive
      predictive value (PPV), and a 83.33% negative predictive value (NPV); while the 7
      degrees  cut-off point had a 78.26% sensitivity, a 88.88% specificity, a 85.7%
      PPV, and a 82.7% NPV. Conclusion: The prevalence rate of AIS in Surabaya is 2.93%
      and the 7 degrees  cut-off point of inclination angle is suitable for school
      based screening.

PMID- 29326759
TI  - Exercise Inhibits the Effects of Smoke-Induced COPD Involving Modulation of
      STAT3.
AB  - Purpose: Evaluate the participation of STAT3 in the effects of aerobic exercise
      (AE) in a model of smoke-induced COPD. Methods: C57Bl/6 male mice were divided
      into control, Exe, COPD, and COPD+Exe groups. Smoke were administered during 90
      days. Treadmill aerobic training begun on day 61 until day 90. Pulmonary
      inflammation, systemic inflammation, the level of lung emphysema, and the airway
      remodeling were evaluated. Analysis of integral and phosphorylated expression of
      STAT3 by airway epithelial cells, peribronchial leukocytes, and parenchymal
      leukocytes was performed. Results: AE inhibited smoke-induced accumulation of
      total cells (p < 0.001), lymphocytes (p < 0.001), and neutrophils (p < 0.001) in
      BAL, as well as BAL levels of IL-1beta (p < 0.001), CXCL1 (p < 0.001), IL-17 (p <
      0.001), and TNF-alpha (p < 0.05), while increased the levels of IL-10 (p <
      0.001). AE also inhibited smoke-induced increases in total leukocytes (p <
      0.001), neutrophils (p < 0.05), lymphocytes (p < 0.001), and monocytes (p < 0.01)
      in blood, as well as serum levels of IL-1beta (p < 0.01), CXCL1 (p < 0.01), IL-17
      (p < 0.05), and TNF-alpha (p < 0.01), while increased the levels of IL-10 (p <
      0.001). AE reduced smoke-induced emphysema (p < 0.001) and collagen fiber
      accumulation in the airways (p < 0.001). AE reduced smoke-induced STAT3 and
      phospho-STAT3 expression in airway epithelial cells (p < 0.001), peribronchial
      leukocytes (p < 0.001), and parenchymal leukocytes (p < 0.001). Conclusions: AE
      reduces smoke-induced COPD phenotype involving STAT3.

PMID- 29326762
TI  - Outcome Determinants of Patients with Traumatic Pelvic Fractures: A Cohort Study
      in a Level I Trauma Center in Southern Iran.
AB  - Pelvic fracture is a result of devastating injuries and is usually encountered in
      conjunction with other life-threatening injuries. The aim of the current study
      was to determine the outcome determinants of patients with pelvic fractures
      referred to a large trauma center in southern Iran. This retrospective cross
      sectional study was conducted in a level I trauma center over a period of three
      years from 2012 to 2015. We included all patients with pelvic fractures whose
      medical records had sufficient data. Data were compared between good condition
      and poor conditions. A total of 327 patients with mean age of 40.1 +/- 19.7 years
      were included. Poor condition was defined as being associated with higher heart
      rate (p=0.002), lower systolic blood pressure (p<0.001), lower diastolic blood
      pressure (p=0.002) lower Glasgow Coma Scale (GCS) on admission (p<0.001) and
      higher Injury Severity Score (ISS) (p<0.001). Those with poor conditions had
      significantly higher admission to ICU (p<0.001), higher rate of surgical
      interventions (p<0.001) and higher mortality (p<0.001). The hospital length of
      stay (p<0.001) and ICU length of stay (p=0.025) were also longer in those with
      poor condition. Lower hemoglobin, lower pH, higher heart rate, lower systolic
      blood pressure, lower GCS on admission and higher ISS were important outcome
      determinants of traumatic pelvic fractures.

PMID- 29326763
TI  - Incidence of Varus Malalignment Post Interlocking Nail in Proximal Femur Shaft
      Fractures Comparing Two Types of Entry Points.
AB  - Introduction: Osteosynthesis of the femur using an interlocking nail is the gold
      standard for treating diaphyseal fractures of the femur. There are two
      established entry points for the antegrade interlocking nails which is the
      piriformis fossa or the greater trochanter. It has been reported that varus
      malalignment was frequently seen in proximal femur fracture which were treated
      with interlocking nail utilizing the greater trochanter entry point. The study
      was done to find out if the problem was of significance. Materials and Methods:
      This was a retrospective study which included 179 patients with femur fractures
      which were treated from January 2013 till September 2015 in one Hospital. They
      were treated with interlocking nail either by utilizing the piriformis fossa (PF)
      or the greater trochanter (GT) entry points. Post-operative radiographs of the
      femur were used to measure the varus deformity. Results: Out of 179 patients,
      there were 5 patients who were reported to have unacceptable varus malalignment
      (2.79%). These 5 patients were out of the 88 (5.68%) patients utilizing the
      greater trochanter as the entry point. The same 5 patients were out 90 patients
      that were diagnosed with proximal femur shaft fractures (5.55%). Analysis with
      logistic regression was statistically not significant. Conclusion: There was
      higher rate of varus malalignment seen in proximal femur shaft fractures treated
      with interlocking nails utilizing the greater trochanter entry point. The
      incidence of varus malalignment was not significant statistically.

PMID- 29326764
TI  - A Prospective Study to Evaluate the Management of Sub-trochanteric Femur
      Fractures with Long Proximal Femoral Nail.
AB  - Introduction: Sub-trochanteric fractures of the femur remains one of the most
      challenging fractures faced by orthopaedic surgeons. This study was done to
      analyse the management and complications of sub-trochanteric fractures using long
      proximal femoral nail (PFN). Materials and Methods: This was a prospective study
      of 50 patients with sub-trochanteric fractures of femur who were treated with
      long PFN at a tertiary care center from July 2012 to June 2016. The fractures
      were classified according to Seinsheimer classification. All patients were
      assessed functionally by Harris Hip Score. Results: Average duration of union was
      17.08 weeks (range 13 to 32 weeks), union was achieved in 92% cases. Closed
      reduction was achieved in 68% cases and open reduction was required in 32% cases.
      Various intraoperative complications were seen in 12% and delayed complications
      in 26% of cases. Good anatomical results were achieved in 86% of cases and 14%
      were fair. As per Harris Hip score, excellent results were noted in 28% cases,
      good in 56% cases and fair in 16% cases. Conclusion: The long PFN is a reliable
      implant for subtrochanteric femur fractures, with high rate of bone union and
      minimal soft tissue damage. Intramedullary fixation has biological and
      biomechanical advantages, but the surgery is technically demanding.

PMID- 29326765
TI  - Pneumocephalus Following Combined Spinal Epidural Anaesthesia for Total Knee
      Arthroplasty: A Case Report.
AB  - The authors describe a case of pneumocephalus following epidural anaesthesia for
      total knee arthroplasty. Multiple attempts in locating the epidural space for the
      anaesthesia and the use of loss of resistance to air (LORA) technique were
      identified as the source of air entry. Supportive management was given including
      high flow oxygenation therapy and spontaneous reabsorption of air was noted five
      days after surgery. The presence of pneumocephalus should be kept in mind if
      patient develops neurological complications postoperatively following epidural
      anaesthesia.

PMID- 29326766
TI  - Dorsal Luno-capitate Impingement in a Professional Tennis Player: A Case Report.
AB  - A 30-year old male right handed professional tennis player complained about
      reduced athletic performance, chronic pain and restricted extension of his right
      wrist. Lateral radiograph of the right wrist demonstrated an osteophyte
      projecting from the dorsal lip of the lunate bone. The presence of an osteophyte
      on the lateral radiograph of the lunate along with the history, clinical
      examination, intra-operative findings, and post-operative satisfactory result
      made the diagnosis of dorsal luno-capitate impingement syndrome reasonable.

PMID- 29326767
TI  - Internal Fixation of Only the Distal End in a Bipolar Segmental Clavicle
      Fracture: A Case Report.
AB  - Bipolar segmental clavicle fractures are simultaneous clavicle fractures of both
      proximal and distal ends. Few case reports describing these fractures have been
      published, and the management of these injuries have remained controversial. Non
      operative treatment is likely to result in poor shoulder function due to the
      instability of the fracture in patients with high physical demands. In contrast,
      surgical treatment with fixation of both proximal and distal ends of the clavicle
      possibly may cause life-threatening complications. We present a 74-year old
      female farmer who had injured her left shoulder and was diagnosed with a bipolar
      segmental clavicle fracture. Taking the fracture mechanism into consideration, we
      surgically treated only the distal end of the clavicle fracture with a locking
      plate. The proximal end of the clavicle fracture was treated without surgical
      intervention. Both fracture sites achieved bony union after four months and she
      returned to her activities as a farmer. Quick DASH score was 5.0 with excellent
      results at three years after operation.

PMID- 29326768
TI  - Streptococcus Constellatus Spondylodiscitis in a Teenager: A Case Report.
AB  - Streptococcus constellatus is an extremely rare cause of pyogenic
      spondylodiscitis. Literature search yielded only one case report in an elderly 72
      years old man with spontaneous T10-T11 S. constellatus spondylodiscitis. It is
      virtually unheard of in young teenage. We report the case of a 14 years old male
      teenager who presented with worsening low back pain for one year with no
      neurological deficit. Imaging studies were consistent with features of L4-L5
      spondylodiscitis. CT guided biopsy grew a pure culture of streptococcus
      constellatus sensitive to penicillin and erythromycin. He showed full recovery
      with six weeks of intravenous antibiotics. Due to the insidious onset, this case
      highlight the importance of high clinical suspicion and early diagnosis, with
      image guided biopsy followed by treatment with appropriate intravenous
      antibiotics to enable full recovery without further neurological deterioration.

PMID- 29326769
TI  - Osteoradionecrosis in Subaxial Cervical Spine - a Rare and Devastating
      Complication: A Case Report.
AB  - Osteoradionecrosis, a rare complication of radiation therapy, is a slow
      progression disease which affects the surrounding structures of spinal
      components. It essentially weakens the soft tissue and bony configuration and can
      cause nerve impingement or cord compression. We describe a patient who underwent
      radiotherapy for thyroid cancer and presented with cervical kyphosis with
      anterolisthesis of C3/C4 and C4/C5 some 32 years later. We explore the role of
      anterior and posterior fusion, as well as hyperbaric oxygen therapy in promoting
      healing.

PMID- 29326770
TI  - Migratory Bone Marrow Edema Syndrome of the Hips: A Case Report.
AB  - Migratory bone marrow edema syndrome (BMES) of the hip is a rare entity. We
      report the case of a 41-year old male with migratory BMES of the hip with eight
      months interval period between onset of the pain and consultation. This patient
      was successfully treated non-surgically. It is important to always inform the
      patient with unilateral BMES of the hip regarding the possibility of future
      involvement of the contralateral hip.

PMID- 29326771
TI  - Dystrophic Scoliosis in Neurofibromatosis and Rib-head Resection: A Case Report.
AB  - Surgical management of scoliosis in Neurofibromatosis type I may be challenging
      at times especially when dealing with dystrophic curves. We highlight the
      importance of meticulous study of the radiological imaging and careful pre
      operative planning in a patient with dystrophic scoliosis.

PMID- 29326772
TI  - Posterior Elbow Dislocation with Brachial Artery Thrombosis Treated Non
      surgically: A Case Report.
AB  - The brachial artery is rarely injured in closed posterior dislocation of the
      elbow, unlike the high rate of vascular injury seen after dislocation of the
      knee. Despite the anatomical proximity of the brachial artery to the elbow joint,
      most cases of brachial artery injury after dislocation of the elbow are related
      to an associated fracture, an open injury or high-energy trauma. A high index of
      suspicion should be maintained as well as a thorough neurovascular examination
      with regards this potentially disastrous complication. We describe an unusual
      case of complete thrombosis of the brachial artery presenting with a posterior
      elbow dislocation following a fall (low energy trauma) that was treated
      nonoperatively. At three months follow-up, patient had good circulation over the
      affected limb, no complaints of ischemic pain or cold intolerance, no signs of
      Volkmann's ischemic contracture, and a range of motion that was comparable to the
      contralateral limb.

PMID- 29326773
TI  - Clinical Outcomes of Patients Undergoing Rotational Atherectomy Followed by Drug
      eluting Stent Implantation: A Single-center Real-world Experience.
AB  - Background: Rotational atherectomy (RA) is used to improve procedural success of
      percutaneous catheter interventions (PCIs) of complex and heavily calcified
      coronary lesions. We report the clinical experience and outcomes in our
      institution with the use of RA, followed by drug-eluting stent implantation.
      Materials and Methods: Data of 81 patients treated with PCI and adjunctive RA
      were analyzed. Clinical follow-up for the occurrence of major adverse events
      (MAEs) was obtained in all patients and correlated with significant variables
      using multivariate Cox proportional hazards analysis. Results: Mean age was 67.9
      +/- 9.2 years, 61.7% had diabetes, 20.9% had chronic kidney disease, and 48.1%
      had previous acute coronary syndrome (ACS). Mean SYNTAX score was 29.8 +/- 12.2,
      with a 92.5% angiographic success rate achieved. In-hospital MAEs rate was 7.4%
      while mortality rate was 8.6%. On median follow-up of 12.2 months, incidence of
      MAEs of 13.5% with a 75% free incidence from MAEs at 34 months. Multivariate
      analysis revealed that a history of previous ACS, ejection fraction, neutrophil
      to lymphocyte ratio, platelet to lymphocyte ratio, SYNTAX score, burr to artery
      ratio, and attainment of angiographic success were significant predictors of
      MAEs. Conclusion: RA followed by drug-eluting stent implantation is a safe and
      effective method in improving procedural success as well as short- and long-term
      outcomes of PCI in our center. A combination of clinical and procedural factors
      is predictive for the occurrence of MAEs and should be taken into account in the
      application of this technique.

PMID- 29326774
TI  - The Burden of Truncus Arteriosus in an Urban City in Africa: How are we Fairing?
AB  - Background: The true incidence of truncus arteriosus in underdeveloped countries
      is difficult to determine. This is due largely to underreporting as a result of
      nonavailability of technologically advanced facilities to make definitive
      diagnosis prenatally. There is a lack of data on the profile and outcome of
      patients with persistent truncus arteriosus (PTA) in Nigeria. This study aims to
      document the demographic characteristics, mode of presentation, indications for
      echocardiography, associated anomalies, average age at diagnosis, and outcome of
      patients with truncus arteriosus in our center. Methods: Prospective and cross
      sectional involving consecutive patients diagnosed with PTA using
      echocardiography at the Paediatric Department of Lagos State University Teaching
      Hospital, Lagos, Nigeria as part of a large study between January 2008 and
      December 2015. Results: Only 25 patients had PTA during the study period. The
      prevalence of PTA among children presenting at the study center during the study
      period was 7.9/100,000. It constituted 2.4% of the cases of congenital heart
      disease and 7.1% of cases of cyanotic congenital heart disease. The male:female
      ratio was 1:1.1. The ages of the patients at diagnosis ranged between 0.75 and
      153 months with a mean age at diagnosis +/- standard deviation of 18.4 months +/-
      37.7. Only about 40% of patients were diagnosed within the neonatal period.
      Cyanosis was the most frequent indication for evaluation. Conclusion: PTA is as
      common in Nigeria as in the other parts of the world but diagnosed late. Cyanosis
      is the most common presenting feature.

PMID- 29326775
TI  - A Systematic Review on the Prevalence of Acute Myocardial Infarction in Iran.
AB  - In Iran, cardiovascular diseases are the most common causes of death. We aimed to
      perform a systematic review on the prevalence of acute myocardial infarction
      (AMI) in Iran based on Persian and English papers had been published from 1985 to
      2015. Among 267 initially found articles, 142 were excluded; finally, a total
      number of 40 articles were found relevant which were reduced to 18. Smoking,
      hypertension, diabetes mellitus, and hypercholesterolemia were the most common
      risk factors for AMI. Premature MI prevalence was high in men, and smoking was
      the most common risk factor among young people. People in urban areas were more
      likely to experience AMI than rural people. The prevalence of AMI in Iran is high
      and has increased in recent years. Therefore, to restrain the rising trend of
      AMI, it is necessary to make the primary and secondary prevention efforts.

PMID- 29326776
TI  - Aorto-right Ventricular Fistula Following Percutaneous Transcatheter Aortic Valve
      Replacement: Case Report and Literature Review.
AB  - An 88-year-old woman with a prior history of aortic stenosis and history of
      valvuloplasty presented with worsening symptoms of heart failure and dizziness.
      She underwent successful transcatheter aortic valve replacement (TAVR) without
      complications. Follow-up echocardiograms revealed a small fistula connecting
      aorta to the right ventricle. The patient was initially asymptomatic but 3 months
      later developed overload of the right ventricle and heart failure and chose to
      continue medical therapy. She died of progressive heart failure at 9 months from
      onset of fistula. Aorto-right ventricular fistula is a rare complication of TAVR
      with only four cases reported in literature thus far.

PMID- 29326777
TI  - Surgical Treatment of Right Ventricular Rupture Caused by Total Occlusion of the
      Right Coronary Artery.
AB  - The rupture of the right ventricular anterior wall after myocardial infarction is
      a rare and life-threatening complication associated with high mortality. Early
      diagnosis by echocardiographic examination and successful treatment is discussed
      in this case report.

PMID- 29326778
TI  - "Double Ball Valve Mechanism Obstructing Both Right Ventricular Inflow and
      Outflow": Atypical Presentation of Right Atrial Myxoma Presenting as Right
      Ventricular Mass.
AB  - Large intracavitary masses such as those occupying most of a cardiac chamber and
      obstructing blood flow are not routinely encountered in clinical practice. The
      differential diagnosis includes neoplastic as well as nonneoplastic causes.
      Primary cardiac tumors by themselves are uncommon. We hereby report a rare case
      of a middle-aged female presenting with New York Heart Association Class III
      symptoms, whose transthoracic echocardiogram revealed a huge mass in right-sided
      chambers with a novel double ball valve type movement. She successfully underwent
      urgent surgical resection of the mass with histopathological confirmation of
      diagnosis.

PMID- 29326779
TI  - Tacrolimus as a Rare Cause of Pericardial Effusion in a Renal Transplant
      Recipient.
AB  - Pericardial effusion in a renal transplant recipient represents a diagnostic
      conundrum with a variety of differential diagnoses. Immunosuppressive medications
      such as sirolimus have been linked to pericardial effusions in the reported
      literature. Tacrolimus has been reported to be associated with pleural effusions
      and ascites. We present a case of a patient with tacrolimus as the likely cause
      of a recurrent pericardial effusion.

PMID- 29326780
TI  - Cardiac Magnetic Resonance of Myocardial Involvement in Leptospirosis.
AB  - Leptospirosis is a zoonotic infection caused by the Leptospira interrogans.
      Although it is endemic in tropical countries, global incidence has increased in
      several temperate and developed regions. Here, we present a cardiac magnetic
      resonance (CMR) and multidetector computer tomography (MDCT) chest features of
      active systemic leptospiral infection in a 19-year-old male. The MDCT appearances
      of lungs and CMR appearances of myocardium in icteric leptospirosis are
      described. Early diagnosis and prompt treatment is important to manage the
      cardiothoracic complications.

PMID- 29326782
TI  - The Art of a Medical Illustrator.

PMID- 29326781
TI  - Myxoma in Left Atrium.

PMID- 29326783
TI  - The Physician's Oath: Historical Perspectives.

PMID- 29326784
TI  - Auto-transplantation of whole rat ovary in different transplantation sites.
AB  - This study was carried out to assess the different ovarian transplantation sites
      after short-time autografting. Female rats were randomized into five groups, with
      six rats in each group, including control (intact), cervical subcutaneous
      transplanted (CST), back subcutaneous transplanted (BST), subfascial transplanted
      (SFT) and intramuscular transplanted (IMT) groups. In all experimental groups,
      the right ovary was removed and transplanted into different sites. After three
      weeks, ovaries were removed for morphology assessment, follicular counting and
      the rates of corpus luteum (CL) and cyst formation. Transplanted ovaries in BST
      and SFT groups were full of cysts and did not have sufficient numbers of intact
      follicles and were excluded from experiments. In IMT and CST groups, re
      anastomosis, follicular development and good homogeneity of the stromal tissue
      were seen. However, the difference in intact antral follicles between CST (7.92
      +/- 0.02%) and CST-Op (opposite ovary of CST group) (30.99 +/- 0.03%) was
      significant as well as the difference between CST (7.92 +/- 0.02%) and control
      (10.08 +/- 0.01%) groups. In addition, the number of intact primordial follicles
      in the CST-Op (16.58 +/- 0.02%) group was significantly less than that of the
      control (40.40 +/- 0.03%) group. Interestingly, the number of CL was
      significantly increased in the CST-Op (11.71 +/- 0.01%) and IMT-Op (9.16 +/-
      0.02%) groups compared to the control and experimental groups. Although both
      intramuscular and subcutaneous sites effectively preserved ovarian follicles
      after three weeks, cervical subcutaneous site was better suited for auto
      transplantation in rat.

PMID- 29326785
TI  - Effect of Satureja khuzestanica essential oil against fertility disorders induced
      by busulfan in female mice.
AB  - Busulfan is an alkylating agent affects ovarian follicles growth by oxidative
      stress induction. Satureja khuzestanica has antioxidant effects. The aim of this
      study was to examine whether S. khuzestanica essential oil (SKEO) exhibits
      protective effects on busulfan-induced ovarian failure. Eighty-four adult female
      mice were divided into six groups including dimethyl sulfoxide (control), SKEO
      225.00 mg kg-1 (orally), busulfan 3.00 mg kg-1 (orally), busulfan 36.00 mg kg-1
      (intraperitoneally), busulfan 3.00 mg kg-1 and SKEO and busulfan 36.00 mg kg-1
      and SKEO. After 28 days, the mice were euthanized and oocytes were removed for in
      vitro fertilization (IVF) rate evaluation. Oocyte quantity and quality,
      fertilization rate and pre-implantation embryo development were daily examined
      with a stereo microscope in a period of 120 hr. Serum levels of estradiol and
      progesterone were also evaluated. Busulfan caused significant decreases in oocyte
      number and quality, fertilization rate, pre-implantation embryo development and
      embryo quality. The SKEO significantly decreased the adverse effects of busulfan.
      The present study indicated that SKEO can protect female fertility potential
      against busulfan induced damages.

PMID- 29326786
TI  - Molecular identification and phylogenetic analysis of chronic bee paralysis virus
      in Iran.
AB  - Chronic bee paralysis virus (CBPV) is an unclassified polymorphic single-stranded
      RNA virus. Among the viruses infecting honeybees, CBPV is known to induce
      significant losses in honeybee colonies. In this study, a total number of eighty
      nine suspected apiaries from four regions of Iran (including Mazandaran, Khorasan
      Razavi, Hormozgan, and Kurdistan) were sampled and submitted for molecular
      identification. Three positive samples were detected by RT-PCR. All positive
      samples were confirmed by sequencing. The phylogenetic tree which displays the
      molecular relationship between the viruses of different Iranian geographic
      regions and references isolates was constructed. The Iranian isolates formed two
      distinct phylogenetic groups (Group 1 and Group 2). The IR-CPV-GMG-1, IR-CPV-GMG
      2, IR-CPV-GMG-4, and IR-CPV-GMG-6 formed Group 1 and IR-CPV-GMG-3, IR-CPV-GMG-5,
      and IR-CPV-GMG-7 were in Group 2 as a distinct group. Iranian isolates in group 1
      were similar to European and East Asian CBPVs. This research was the first
      phylogenetic analysis of CBPV in Iran. Further researches are needed to study the
      other aspects of this virus-like genetic characteristics and pathogenesis in
      Iran.

PMID- 29326787
TI  - Molecular detection and phylogenetic analysis of Mycoplasma gallisepticum from
      backyard and commercial turkey flocks in Iran.
AB  - Mycoplasma gallisepticum (MG) is economically important pathogen of poultry
      causes airsacculitis and frequently infraorbital sinusitis in turkeys. Infections
      may remain without clinical signs, but they can make birds susceptible to
      secondary infections. This study was carried out for molecular detection and
      phylogenetic analysis of MG infections in commercial and backyard turkey flocks
      in some parts of Iran. A total number of 600 swab samples were collected from 18
      commercial and 31 backyard turkey flocks. The PCR technique was performed for
      detecting 16S rRNA gene in the samples. Positive sample were subjected for
      sequencing of mgc2 gene. The results showed that 48.38% of backyard and 16.66% of
      commercial farms were positive for MG. These findings suggested the presence of
      MG in the commercial and backyard turkeys' farms of Iran. The molecular analysis
      indicated high sequence similarity between some Iranian turkeys isolates with
      Indian and Pakistanian MG isolates. Furthermore, substitutions of MG nucleic
      acids and correlated amino acids sequences may lead to some antigenic
      modifications.

PMID- 29326788
TI  - A molecular study on Babesia spp. in cattle and ticks in West-Azerbaijan
      province, Iran.
AB  - A total number of 450 blood samples were collected from 45 different randomly
      selected cattle herds. Light microscopic examination of blood smears revealed
      Babesia spp. infection in 4.2%, while 8.9% of blood samples were positive using
      PCR. Upon multiplex-PCR (mPCR), B. bigemina and B. bovis infections were detected
      in 37/40 (92.5%) and 3/40 (7.5%) samples, respectively. 530 ticks of 10 Ixodid
      species were collected from the same cattle. Hyalomma anatolicum was the most
      prevalent tick species (19.9%). An expected 520 bp fragment of Babesia spp. was
      generated in 22 (48.8%) of Rhpicephalus annulatus, 18 (40.0%) of R. bursa and 12
      (30.0%) R. sanguineus sensu lato. The mPCR findings revealed that all infected
      ticks including R. annulatus, R. bursa and R. sanguineus were totally infected
      with B. bigemina. The DNA amplification of B. bovis and B. bigemina in egg
      samples showed that only B. bigemina was detected in two specimens of R.
      annulatus. It could be concluded that B. bigemina was the dominant causative
      agent in this region but the evidence of B. bovis infection of cattle in a few
      cases was noted, as well. The results suggested that B. bigemina and B. bovis
      could be detected in the DNA extracted from R. annulatus, R. bursa and R.
      sanguineus sensu lato confirming previous reports. Since B. bigemina is
      transmitted transovarially by R. annulatus, it might act as an important vector
      for B. bigemina.

PMID- 29326790
TI  - Microbiological, biochemical and organoleptic properties of fermented-probiotic
      drink produced from camel milk.
AB  - The microbiological and biochemical changes occurred during the fermentation of
      camel milk inoculated by three selected bacterial starter, were investigated as
      well as the sensory evaluation of the product. Milk samples were collected from
      camel herds of southeastern of Iran. Chr. Hansen ABT-10 starter including
      Lactobacillus acidophillus, Biphidobacterum biphidum and Sterptococcus
      thermophilus in ratio of 0.50 g per 100 mL of camel milk was added. This
      fermented product was examined at the 0, 3rd, 6th and 9th days for
      microbiological, biochemical and sensory evaluations. The results showed the
      number of starter bacteria was maintained at least 106 CFU mL-1 during nine test
      days. It was shown that it could be used as fermented-probiotic drink. The
      product did not show any microbial contamination. The acidity and protein amount
      of produced drink showed a significant (p < 0.05) increase in different test
      days. Fat, solids-not-fat and ash amount of the product showed significant
      differences at the ninths' test day compared to the zero test day (p < 0.05).
      Organoleptic properties of product including flavor, color, odor, consistency,
      mouth feel and overall acceptance were significantly improved (p < 0.05).
      Therefore, the produced fermented-probiotic drink, in addition to keep
      maintenance and increased nutritional quantity value, was accepted by consumers
      in terms of organoleptic properties and it could be used as a healthy and
      functional drink.

PMID- 29326789
TI  - Production and purification of polyclonal antibody against F(ab')2 fragment of
      human immunoglobulin G.
AB  - Antibodies are essential tools of biomedical and biochemical researches.
      Polyclonal antibodies are produced against different epitopes of antigens.
      Purified F(ab')2 can be used for animal's immunization to produce polyclonal
      antibodies. Human immunoglobulin G (IgG) was purified by ion exchange
      chromatography method. In all stages verification method of the purified
      antibodies was sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS
      PAGE). Purified IgG was digested by pepsin enzyme and F(ab')2 fragment was
      purified by gel filtration separation method. For production of polyclonal
      antibody, rabbit was immunized by purified F(ab')2 and antibody production was
      investigated by enzyme-linked immunosorbent assay. Purified anti-IgG F(ab')2 was
      conjugated with fluorescein isothiocyanate. Ion exchange chromatography
      purification yielded 38 mg of human IgG antibody. The results of SDS-PAGE in
      reduced and non-reduced conditions showed bands with 25-30 kDa molecular weight
      (MW) and 50-kDa respectively and a distinct band with 150 kDa MW. The results of
      non-reduced SDS-PAGE for determining the purity of F(ab')2 fragment showed one
      band in 90 kDa and a band in 150 kDa MW position. Purification by Ion exchange
      chromatography method resulted about 12 mg rabbit polyclonal antibody. Flow
      cytometry showed generated polyclonal antibody had an acceptable activity
      compared to commercial antibody. Taking together, purified IgG F(ab')2 and
      polyclonal anti-IgG F(ab')2 are useful tools in biomedical and biochemical
      researches and diagnostic kits.

PMID- 29326791
TI  - Effect of chlorpyrifos on sperm characteristics and testicular tissue changes in
      adult male rats.
AB  - Chlorpyrifos (CPF) is a broad spectrum organophosphate pesticide used for
      agricultural health purposes. Its principal mechanism of toxicity is the
      inhibition of acetylcholinesterase. The purpose of present study was to
      investigate the effects of CPF on testicular tissue and sperm parameters in male
      rats. Thirty-two healthy male rats were divided into two groups: a CPF-exposed
      group and a control-sham group. Control-sham group received corn oil (0.20 mL per
      day). The CPF was administered orally to male rats at 37 mg kg-1 BW for 45 days
      to evaluate the reproductive toxicity. In all rats, sampling for histological and
      sperm analyses was performed on days 5, 15, 30 and 45. The CPF caused a
      significant (p < 0.05) decrease in sperm count, viability and motility and
      increased immature sperms and DNA damage in sperm cells. Light microscopic
      analyses revealed increased arrested spermatogenesis, negative tubular
      differentiation and repopulation indexes and decreased Leydig cells number. These
      findings indicate that CPF has adverse effects on sperm cells and reproductive
      system of male rats.

PMID- 29326792
TI  - Florfenicol pharmacokinetics following intravenous and oral administrations and
      its elimination after oral and bath administrations in common carp (Cyprinus
      carpio).
AB  - The aim of this study was to evaluate pharmacokinetic profiles of florfenicol
      after a single dose of intravenous (5.00 mg kg-1 body weight) and oral (40.00 mg
      kg-1 body weight) administrations in common carp (Cyprinus carpio). The residue
      depletion of florfenicol was also investigated after oral administration (10.00
      mg kg-1 body weight) and bath treatment (5.00 mg L-1) for 10 consecutive days.
      Pharmacokinetics of florfenicol in plasma after a single dose administration, at
      10 time points (0.50, 1, 2, 4, 8, 12, 24, 72, 120 and 168 hr) and florfenicol
      concentrations in tissues (plasma, liver and muscle) at three time points (1, 7
      and 14 days) after 10 consecutive days, were analyzed by high performance liquid
      chromatography. The peak concentration of florfenicol was 137.02 ng mL-1 and the
      time to reach peak concentration in plasma was two hr. The elimination half
      lives, the volume of distribution at steady state and total body clearance were
      estimated as 21.40 hr, 0.30 and 0.03 L hr-1, respectively. After drug
      administration for 10 days, it's concentration in plasma and muscle in oral
      treatment was significantly more than bath treatment in all days. Drug
      concentrations in the liver after bath treatment were significantly higher for a
      shorter period than the concentration in the oral treatment, indicating that
      higher levels of florfenicol for a longer period can be achieved in the tissues
      after oral drug administration. According to pharmacokinetic results, florfenicol
      may be a suitable candidate for the treatment of common bacterial infections in
      common carp farming.

PMID- 29326793
TI  - European pond turtle (Emys orbicularis persica) as a biomarker of environmental
      pollution in Golestan and Mazandaran provinces, Iran.
AB  - Anthropogenic environmental changes are hypothesized as main reasons for animal
      species population declines. Heavy metals contamination is one of the worst
      threats to animals among human-caused threats. As most of the heavy metals
      bioaccumulate in organisms, analyzing concentrations of heavy metals in long
      living animals, such as turtles, would be very useful for biomonitoring of
      environmental quality. The European pond turtle is classified as a Near
      Threatened in the red list of International Union for Conservation of Nature. The
      objective of this study was to obtain information on heavy metals contamination
      in this species, as a sentinels, to evaluate the overall health of both the
      European pond turtles and their ecosystem in Golestan and Mazandaran provinces.
      Biological samples of 10 living and 15 dead European pond turtles were analyzed
      by atomic absorption spectrophotometer for Zn, Pb, Cu, and Cd contaminations.
      Highest concentration of Zn (202.6 +/- 58.5 MUg g-1), Cd (4.4 +/- 1.3 MUg g-1)
      and Cu (3.8 +/- 1.7 MUg g-1) was detected in livers and the highest accumulation
      of Pb (45.6 +/-16.3 MUg g-1) occurred in kidneys. Positive correlations were
      detected among Zn, Pb and Cd tissue concentrations and carapaces curve length.
      Heavy metal levels were higher in males than females. Heavy metals contamination
      of sampled turtles stood in high degree. However, there is clearly a need to
      evaluate heavy metals physiologic effects on European pond turtles.

PMID- 29326795
TI  - Molecular detection of Ehrlichia spp. in blood samples of dogs in southern Iran
      using polymerase chain reaction.
AB  - Ehrlichiosis is a zoonotic disease which has been reported from some regions of
      Iran. This study was aimed to determine the presence and prevalence of
      ehrlichiosis in suspected dogs referred to the Faculty of Veterinary Medicine,
      Shiraz University, Shiraz, Iran using polymerase chain reaction (PCR). Blood
      samples were collected from 98 suspected dogs with at least one of the five
      following findings: thrombocytopenia, anemia (hematocrit < 37.00%),
      gastrointestinal signs and respiratory and/or central nervous system diseases.
      Complete blood count was performed for each sample. After genomic DNA extraction,
      PCR assay was carried out using a commercial PCR kit. The results showed that
      only three out of 98 samples (3.06%) were positive for ehrlichiosis. There was no
      significant difference in hematological parameters between infected and non
      infected cases. These results emphasize that ehrlichiosis has a low prevalence
      among examined cases in southern Iran. Further serological and molecular studies
      are needed to clarify the epidemiological feature of this infection in different
      areas of Iran.

PMID- 29326794
TI  - Effects of bisphenol-S low concentrations on oxidative stress status and in vitro
      fertilization potential in mature female mice.
AB  - Bisphenol-S (BPS) is a new bisphenol-A substitute widely used in many plastic
      products. Bisphenol-A as a main member of bisphenol family has been known as an
      endocrine system disrupter chemical compound. Like other members of bisphenol
      family, there is public health concern about the toxic effects of BPS on
      reproductive system, thus, we examined BPS effects on in vitro fertilization
      (IVF) potential and oxidative stress status in a murine model. Adult female mice
      (n = 70) were randomly divided into control and BPS-treated groups. Bisphenol-S
      was administered at doses of 0, 1, 5, 10, 50 and 100 ug kg-1 body weight per day
      intraperitoneally for 21 consecutive days. Twenty-Four hr after the last
      treatment, five mice in each group were super-ovulated and the oocytes were
      harvested for IVF. All ovaries were collected and used for biochemical factors
      analyses. Bisphenol-S exposure at doses more than 10 ug kg-1 induced
      developmental arrest of pre-implantation embryos. Further, lipid peroxidation
      measurement in ovaries indicated that all doses of BPS cause oxidative stress in
      female mice. In conclusion, BPS administration even in low doses can result in
      female reproductive toxicities and oxidative stress in mice.

PMID- 29326796
TI  - Effect of different levels of dietary vitamin E on reproductive and productive
      performances in Japanese quails (Coturnix coturnix japonica).
AB  - The aim of this study was to evaluate the effects of dietary vitamin E on
      reproductive and productive parameters in Japanese quails. A total number of 240
      female and 80 male Japanese quail were divided into five treatments with four
      replications in a completely randomized design. Experimental diets were zero
      control, 30, 60, 120 and 240 mg kg-1 of vitamin E. Fertility and total
      hatchability were not affected by treatments. But, the lowest hatch of fertile
      eggs and the highest embryonic death were observed in control group (p < 0.05).
      Left testes weight in T2 and T4 was higher than control (p < 0.05). Right testes
      weight and sera FSH concentration in males were not affected by treatments. The
      highest testosterone concentration of males was observed in T5 (p < 0.05). Weight
      and length of oviduct as well as weight of ovary and FSH concentration in females
      did not affected by treatments. Estrogen concentration in T4 treatment was
      greater than control (p < 0.05). Most of the egg characteristics were not
      affected by treatments. However, higher egg mass and production rates were
      observed in T2 and T3groups than control group (p < 0.05). Feed intake and
      conversion ratio did not differ among treatments. In conclusion, dietary vitamin
      E improved hatch of fertile egg, embryonic viability, egg mass and production
      rates in Japanese quail. The effect of dietary vitamin E combined with selenium
      on these characteristics are recommended for future study in Japanese quail.

PMID- 29326797
TI  - Congenital lumbar vertebrae agenesis in a lamb.
AB  - Congenital agenesis of lumbar vertebrae was diagnosed in a day-old female lamb
      based on radiology and clinical examinations. There was no neurological deficit
      in hindlimb and forelimb associated with standing disability. Radiography of the
      abdominal region revealed absence of lumbar vertebrae. Necropsy confirmed
      clinical and radiographic results. No other anomaly or agenesis was seen
      macroscopically in the abdominal and thoracic regions as well as vertebral
      column. Partial absence of vertebral column has been reported in human and
      different animal species, as an independent occurrence or associated with other
      organs anomalies. The latter has been designated as caudal regression syndrome.
      Vertebral agenesis may arise from irregularity in the differentiation of somites
      to the sclerotome or sclerotome to the vertebral primordium. Most of the
      previously reported cases of agenesis were related to the lumbosacral region,
      lonely or along with other visceral absences. This case was the first report of
      congenital agenesis of lumbar vertebrae in a lamb.

PMID- 29326798
TI  - Late-Onset Hepatic Veno-Occlusive Disease after Allografting: Report of Two Cases
      with Atypical Clinical Features Successfully Treated with Defibrotide.
AB  - Hepatic Veno-Occlusive Disease (VOD) is a potentially severe complication of
      hematopoietic stem cell transplantation (HSCT). Here we report two patients
      receiving an allogeneic HSCT who developed late onset VOD with atypical clinical
      features. The two patients presented with only few risk factors, namely, advanced
      acute leukemia, a myeloablative busulphan-containing regimen and received grafts
      from an unrelated donor. The first patient did not experience painful
      hepatomegaly and weight gain and both patients showed only a mild elevation in
      total serum bilirubin level. Most importantly, the two patients developed
      clinical signs beyond day 21 post-HSCT. Hepatic transjugular biopsy confirmed the
      diagnosis of VOD. Intravenous defibrotide was promptly started leading to a
      marked clinical improvement. Based on our experience, liver biopsy may represent
      a useful diagnostic tool when the clinical features of VOD are ambiguous. Early
      therapeutic intervention with defibrotide represents a crucial issue for the
      successful outcome of patients with VOD.

PMID- 29326800
TI  - Sterile 'Abscess' of the Spleen and the Sickle Cell Trait.

PMID- 29326799
TI  - Molecular Heterogeneity in Acute Promyelocytic Leukemia - a Single Center
      Experience from India.
AB  - Atypical breakpoints and variant APL cases involving alternative chromosomal
      aberrations are seen in a small subset of acute promyelocytic leukemia (APL)
      patients. Over seven different partner genes for RARA have been described.
      Although rare, these variants prove to be a diagnostic challenge and require a
      combination of advanced cytogenetic and molecular techniques for accurate
      characterization. Heterogeneity occurs not only at the molecular level but also
      at clinico-pathological level influencing treatment response and outcome. In this
      case series, we describe the molecular heterogeneity of APL with a focus on seven
      variant APL cases from a single tertiary cancer center in India over a period of
      two and a half years. We discuss five cases with ZBTB16-RARA fusion and two novel
      PML-RARA variants, including a Bcr3 variant involving fusion of PML exon4 and
      RARA exon3 with an additional 40 nucleotides originating from RARA intron2,
      another involving exon 6 of PML and exon 3 of RARA with addition of 126
      nucleotides, which mapped to the central portion of RARA intron 2. To the best of
      our knowledge, this is the first case series of this kind from India.

PMID- 29326803
TI  - Treatment of Early Stages Hodgkin Lymphoma During Pregnancy.
AB  - Background: To assess maternal and fetal outcome of women and newborns who
      received chemotherapy during pregnancy to treat Hodgkin lymphoma (HL)in early
      stages (IA, IIA), we performed a retrospective analysis of a cohort of 44
      pregnant women with HL and early stages, diagnosed and treated between 1988 to
      2013, at a tertiary reference cancer center. Methods: We analyzed data on HL
      characteristics and treatment, with a particular attention to maternal and fetal
      complications; in children, we performed a longer follow-up to detect any anomaly
      in physical development, scholar performance, psychological, cardiac,
      neurological function, and intelligence tests. Results: Median age was 29.4
      (range 21-37) years; Most patients were stage IIA (86%), had M a bulky
      mediastinal disease (78%) and 60% had > 3 nodal sites involved; thus these
      patients were considered to have a not favorable condition. Abortion was refused
      when it was proposed. All patients received chemotherapy during pregnancy; ABVD
      (adryamicin, bleomycin, vinblastine, and dacarbazine) at standard doses and
      schedule, even during the first trimester. Radiotherapy, when indicated, was
      administered after delivery in 39 patients. No obstetrical complications were
      observed, delivery occurred between 33 to 36 weeks in 10 cases (22%); and >37
      weeks in 34 cases (87%). Four newborns were low-weight: 2012 g median (range 1750
      - 2350 g). No clinical malformations were observed, and development of newborns
      was physiological without evidence of cardiac and neurological damage, behavior,
      intelligence, and scholar attendance were normal. At median follow-up range of
      120.4 (48-299) months, the progression-free survival and overall survival of
      patients were 95% and 93%respectively. Conclusion: Combined chemotherapy, as
      initial therapy appears to be the best approach in this setting of patients, with
      an excellent outcome to both mothers and children. If radiotherapy is necessary,
      it could be administered after delivery.

PMID- 29326801
TI  - Waldenstrom's Macroglobulinemia: An Update.
AB  - Waldenstrom Macroglobulinemia is a rare lymphoproliferative disorder with
      distinctive clinical features. Diagnostic and prognostic characterisation in WM
      significantly changed with the discovery of two molecular markers: MYD88 and
      CXCR4. Mutational status of these latter influences both clinical presentation
      and prognosis and demonstrated therapeutic implications. Treatment choice in
      Waldenstrom disease is strictly guided by patients age and characteristics,
      specific goals of therapy, the necessity for rapid disease control, the risk of
      treatment-related neuropathy, disease features, the risk of immunosuppression or
      secondary malignancies and potential for future autologous stem cell
      transplantation. The therapeutic landscape has expanded during the last years and
      the approval of ibrutinib, the first drug approved for Waldenstrom
      Macroglobulinemia, represents a significant step forward for a better management
      of the disease.

PMID- 29326802
TI  - Allogeneic Hematopoietic Stem Cell Transplantation In Therapy-Related Myeloid
      Neoplasms (t-MN) of the Adult: Monocentric Observational Study and Review of the
      Literature.
AB  - Background: Therapy related myeloid neoplasms (t-MN) occur due to direct
      mutational events of chemotherapeutic agents and radiotherapy. Disease latency,
      mutational events and prognosis vary with drugs categories. Methods: We describe
      a cohort of 30 patients, 18 females and 12 males, with median age of 52.5 years
      (range, 20 to 64), submitted to allogeneic stem cell transplantation (HSCT) in
      our department between September 1999 and March 2017. Patients had a history of
      solid tumour in 14 cases, haematological disease in 15 cases and both of them in
      one case. After a median of 36.5 months (range, 4 to 190) from first neoplasm,
      patients developed t-AML in 19 cases and t-MDS in 11 cases. Molecular
      abnormalities were detected in 5 patients, while karyotype aberrations were found
      in 17 patients. Patients received conventional chemotherapy in 14 cases,
      azacitidine in 10 cases and both of them in one case. Five patients were
      submitted to HSCT without previous treatment except for supportive therapy.
      Results: Seventeen patients obtained sustained CR after SCT, while 8 patients
      showed resistant or relapsed disease. The remaining five patients died early
      after SCT. At follow up time (May 2017) 13 patients were alive with a median OS
      of 48 months (range 3-195), while 17 patients died after a median of 4 months
      (range 1-27) by relapse mortality in 6 cases and non-relapse mortality in the
      other 11 patients. Conclusions: Global OS was 43%. After SCT, 72.2% of patients
      with t-MN maintained a sustained CR.

PMID- 29326804
TI  - Occult Hepatitis B Virus Infection and Associated Genotypes among HBsAg-negative
      Subjects in Burkina Faso.
AB  - Background: The presence of HBV DNA in the liver (with detectable or undetectable
      HBV DNA in the serum) of individuals tested HBsAg negative by currently available
      assays is defined occult B Infection (OBI). It remains a potential transmission
      threat and risk to HBV chronic infection. The purpose of this study was to
      determine the OBI prevalence among HBsAg negative subjects and to characterize
      associated genotypes. Methods: Blood samples of 219 HBsAg-negative subjects
      tested by ELISA were collected. HBV DNA was investigated in all samples. Viral
      loads were determined using quantitative real-time PCR. All samples were screened
      for HBV markers (anti-HBc, anti-HBe, HBsAg). The Pre-S/S region of the HBV genome
      was sequenced. The database was analyzed using the SPSS and Epi info software.
      Phylogenetic analysis was performed using the BioEdit and MEGA software. Results:
      Of the 219 samples, 20.1% were anti-HBc positive, 1.8% HBeAg and 22.8% were anti
      HBe positive. Fifty-six (56) (25.6%) of the samples had a detectable HBV DNA and
      viral loads ranging from 4 IU/mL to 13.6 106 IU/mL. Sixteen of them (16/56) had a
      viral load < 200 IU/mL, resulting in an OBI prevalence of 7.3% (16/219) in our
      study. The remaining 40 subjects had viral loads > 200 IU/mL, resulting in a
      "false OBI" prevalence of 18.3% (40/219). HBV genotype E was predominant followed
      by the quasi-sub-genotype A3. A single "false OBI" strain had the characteristic
      mutation G145R. Other mutations were observed and all located in the major
      hydrophilic region (MHR) of the S gene. Conclusion: The study reported a
      prevalence of 7.3% of occult hepatitis B infection. It confirms the predominance
      of genotype E and the existence of a subgroup of quasi-sub-genotype A3 of HBV in
      Burkina Faso. It further provides information on the presence of "false OBI."
      This study has found mutations in the major hydrophilic region (MHR) of the pre
      S/S gene of HBV.

PMID- 29326805
TI  - Detection of beta-Thalassemia Carriers by Red Cell Parameters Obtained from
      Automatic Counters using Mathematical Formulas.
AB  - Background: beta-thalassemia major is a severe disease with high morbidity. The
      world prevalence of carriers is around 1.5-7%. The present study aimed to find a
      reliable formula for detecting beta-thalassemia carriers using an extensive
      database of more than 22,000 samples obtained from a homogeneous population of
      childbearing age women with 3161 (13.6%) of beta-thalassemia carriers and to
      check previously published formulas. Methods: We applied a mathematical method
      based on the support vector machine (SVM) algorithm in the search for a reliable
      formula that can differentiate between thalassemia carriers and non-carriers,
      including normal counts or counts suspected to belong to iron-deficient women.
      Results: Shine's formula and our SVM formula showed >98% sensitivity and >99.77%
      negative predictive value (NPV). All other published formulas gave inferior
      results. Conclusions: We found a reliable formula that can be incorporated into
      any automatic blood counter to alert health providers to the possibility of a
      woman being a beta-thalassemia carrier. A further simple hemoglobin
      characterization by HPLC analysis should be performed to confirm the diagnosis,
      and subsequent family studies should be carried out. Our SVM formula is currently
      limited to women of fertility age until further analysis in other groups can be
      performed.

PMID- 29326806
TI  - Negative Impact of Prolonged Antibiotics or Persistent Diarrhea on Vitamin K1
      Levels in 2-24 Weeks aged Egyptian Infants.
AB  - Background: To evaluate the hazard of prolonged antibiotic therapy and/or
      persistent diarrhea on vitamin K1 (VK1) level and bleeding profile in infants (2
      24 weeks). Methods: A one-year case-control study, conducted at Ain Shams
      University, Egypt. 338 infants (2-24 weeks) were recruited and divided into 3
      groups (1:1:3 ratios); group A (n=67) patients who received antibiotics for >=10
      days, group B (n=67) who had persistent diarrhea >= 14 days and group C (n=204)
      age- and gender- matched infants who had not either received antibiotics nor had
      diarrhea. All subjected to clinical assessment, bleeding history and had their
      complete blood count (CBC), PT and PTT, liver transaminases and VK1 level
      assayed. Results: There was a significant increase in frequency of VKDB (vitamin
      K deficiency bleeding) and abnormal bleeding profile in cases than control group.
      There was significant negative correlation between VK1 level and duration of
      diarrhea, length of antibiotics used and bleeding profile. Antibiotic usage has
      hazardous effect on VK1 level in those with diarrhea; more patients were
      receiving antibiotic in those with persistent diarrhea and VKDB (N=55) than those
      with persistent diarrhea and normal VK1 (N=12). The longer duration of antibiotic
      therapy the lower level of VK1. Combining cephalosporin/penicillin therapy and/or
      diarrhea, in particular, had an impact on VK1 level. Conclusion: VKDB, a
      preventable cause of life-threatening hemorrhage, is still a major health problem
      in Egyptian infants, where persistent diarrhea and misuse of antibiotics are
      prevalent, necessitate a booster dose of VK in those high risk infants.

PMID- 29326807
TI  - Heavy-Chain Diseases and Myeloma-Associated Fanconi Syndrome: an Update.
AB  - The heavy chain diseases (HCDs) are rare B-cell malignancies characterized by the
      production of a monoclonal immunoglobulin heavy chain without an associated light
      chain. There are three types of HCD, defined by the class of immunoglobulin heavy
      chain produced: IgA (alpha-HCD), IgG (gamma-HCD), and IgM (MU-HCD). Alpha-HCD is
      the most common and usually occurs as intestinal malabsorption in a young adult
      from a country of the Mediterranean area. Gamma- and MU-HCDs are rarer and
      associated with a B-cell non-Hodgkin lymphoma that produces an abnormal Ig heavy
      chain. These patients may occasionally be diagnosed with a monoclonal gammopathy
      of undetermined significance (MGUS). Fanconi syndrome, on the other hand, can be
      primary (inherited) or secondary (acquired). The only exception to this rule is
      the idiopathic form. Adult acquired Fanconi syndrome can be a rare complication
      of a monoclonal gammopathy. At diagnosis, most patients have an MGUS or
      smoldering multiple myeloma, with renal failure and evidence of osteomalacia.
      During follow-up, patients can develop an end-stage renal disease. Chemotherapy
      provides little benefit on renal function.

PMID- 29259764
TI  - Utility of massive open online courses (MOOCs) concerning outbreaks of emerging
      and reemerging diseases.
AB  - The emergence and re-emergence of infectious diseases such as Ebola, chikungunya,
      and Zika increase the necessity of knowledgeable and skilled health
      professionals. Massive open online courses (MOOCs) arise as opportunities that
      allow people around the world to participate in higher education courses. A
      search was conducted on specialized MOOC platforms to find courses related to
      outbreaks, using terms included in the list of the WHO disease outbreaks from
      January 1st to December 31 st, 2016. We found seven courses about Ebola, two
      about Zika, three about the dynamics of epidemics and pandemics, and only one
      course about dengue, chikungunya, and malaria. Most of the courses were conducted
      in English. The courses on Ebola, Zika and chikungunya were released after their
      last outbreak. MOOCs could be used to learn about health issues of global
      relevance, and with the necessity of fast divulgation of knowledge and skills.
      Translating the courses into more languages could give these courses more
      traction, and allow participation of professionals in regions affected by these
      outbreaks.

PMID- 29123646
TI  - First de novo draft genome sequence of Oryza coarctata, the only halophytic
      species in the genus Oryza.
AB  - Oryza coarctata plant, collected from Sundarban delta of West Bengal, India,  has
      been used in the present study to generate draft genome sequences, employing the
      hybrid genome assembly with Illumina reads and third generation Oxford Nanopore
      sequencing technology. We report for the first time the draft genome with the
      coverage of 85.71 %  and  deposited the raw data in NCBI SRA, with BioProject ID
      PRJNA396417.

PMID- 29326811
TI  - Impact of liver volume and liver function on posthepatectomy liver failure after
      portal vein embolization- A multivariable cohort analysis.
AB  - Background: Liver failure remains a life-threatening complication after liver
      resection, and is difficult to predict preoperatively. This retrospective cohort
      study evaluated different preoperative factors in regard to their impact on
      posthepatectomy liver failure (PHLF) after extended liver resection and previous
      portal vein embolization (PVE). Methods: Patient characteristics, liver function
      and liver volumes of patients undergoing PVE and subsequent liver resection were
      analyzed. Liver function was determined by the LiMAx test (enzymatic capacity of
      cytochrome P450 1A2). Factors associated with the primary end point PHLF
      (according to ISGLS definition) were identified through multivariable analysis.
      Secondary end points were 30-day mortality and morbidity. Results: 95 patients
      received PVE, of which 64 patients underwent major liver resection. PHLF occurred
      in 7 patients (11%). Calculated postoperative liver function was significantly
      lower in patients with PHLF than in patients without PHLF (67 vs. 109 MUg/kg/h; p
      = 0.01). Other factors associated with PHLF by univariable analysis were age,
      future liver remnant, MELD score, ASA score, renal insufficiency and heart
      insufficiency. By multivariable analysis, future liver remnant was the only
      factor significantly associated with PHLF (p = 0.03). Mortality and morbidity
      rates were 4.7% and 29.7% respectively. Conclusion: Future liver remnant is the
      only preoperative factor with a significant impact on PHLF. Assessment of
      preoperative liver function may additionally help identify patients at risk for
      PHLF.

PMID- 29326812
TI  - Endovascular laser treatment of incompetent saphenous veins using the 1470 nm
      diode laser and radial fiber.
AB  - Objectives: To assess the technical success, complications, and patients' quality
      of life (QoL) after treatment of chronic venous disease (CVD) using the 1470 nm
      radial fiber laser. Methods: A total of 170 patients with chronic venous disease,
      classified as C2 to C4 according to CEAP classification, were treated for
      incompetent greater (GSV) and small (SSV) saphenous veins, using the 1470 nm
      radial fiber laser and application of tumescent anesthesia. Additional
      phlebectomies were performed through stab microincisions, while 11 patients
      further underwent sclerotherapy intraoperatively. Patients' QoL was recorded
      using a CIVIQ-20 questionnaire pre and post-operatively. Results: Technical
      success regarding GSV vein occlusion was recorded at 100% and 98% during 12 and
      24 month follow up respectively. SSV occlusion rates were recorded at 100% for
      the same period. 55% of patients were classified as C2. Mean laser application
      time was 401.1 +/- 92.6 s and 169.4 +/- 56.8 s, while an average of 3986.6 +/-
      934.9 and 1643.5 +/- 534.1 J were applied during ablation of GSV and SSV
      respectively. Three incidents of postoperative pain were recorded. Two patients
      exhibited partial proximal GSV recanalization, while two patients reported mild
      post-operative temporal paresthesia. No major complications were observed post
      operatively. A significant improvement in patients' QoL was demonstrated through
      the CIVIQ-20 questionnaires. Mean pre-operative CIVIQ-20 total score was recorded
      at 77 +/- 3.9, with a total score of 32.8 +/- 2.8 being observed during 12 month
      follow-up. Conclusions: Endovascular laser treatment using the 1470 nm radial
      fiber laser constitutes an effective and safe modality for treatment of CVD.

PMID- 29326808
TI  - Diagnosis of Zollinger-Ellison syndrome in the era of PPIs, faulty gastrin
      assays, sensitive imaging and limited access to acid secretory testing.
AB  - In recent years the diagnosis of Zollinger-Ellison syndrome (ZES) has become
      increasingly controversial with several new approaches and criteria proposed,
      differing from the classical biochemical criterion of inappropriate
      hypergastrinemia (i.e., hypergastrinemia in the presence of hyperchlorhydria)
      (Table 1). These changes have come about because of the difficulty and potential
      dangers of stopping proton pump inhibitors (PPIs) for gastric acid analysis; the
      recognition than many of the current assays used to assess gastrin concentrations
      are unreliable; the development of sensitive imaging modalities that detect
      neuroendocrine tumors (NETs) including an increasing number of the primary
      gastrinomas; the increased use of percutaneous or endoscopic ultrasound (EUS)
      directed biopsies/cytology and the general lack of availability of acid secretory
      testing. In this article we will discuss the basis for these controversies,
      review the proposed changes in diagnostic approaches and make recommendations for
      supporting the diagnosis of ZES in the modern era.

PMID- 29326813
TI  - Surgical treatment of aggressive vertebral hemangioma causing progressive
      paraparesis.
AB  - Vertebral hemangioma is a benign vascular lesion that may onset with neurologic
      symptoms due to spinal cord compression by epidural extension. Surgical
      procedure, embolization and radiotherapy are the gold standard for the treatment
      of this disease. We present a case of a 84 years old woman admitted at our
      department with worsening paraparesis and urinary retention. Her magnetic
      resonance images (MRI) showed a lesion involving both anterior and posterior
      vertebral element of D5, with extension into epidural space and spinal cord
      compression. The patient was operated for laminectomy and epidural lesion
      removal. Histological examination confirmed the diagnosis of cavernous
      hemangioma.

PMID- 29326815
TI  - Case series with literature review: Surgical approach to megarectum and/or
      megasigmoid in children with unremitting constipation.
AB  - Background: The role of surgery in treating children with functional constipation
      (FC) is controversial, because of the efficacy of bowel management programs. This
      case series is comprised of failures: 43 children, spanning 25 years' practice,
      who had megarectosigmoid (MRS) and unremitting constipation. Purpose: To
      determine whether these children were helped by surgery, and to contribute to
      formulating a standard of care for children with megarectum (MR) and/or
      redundancy of the sigmoid colon (MS) who fail medical management. Method: We
      describe our selection criteria and the procedures we utilized - mucosal
      proctectomy and endorectal pull-through (MP) or sigmoidectomy (SE) with
      colorectal anastomosis at the peritoneal reflection. The internet (social media)
      allowed us to contact most of these patients and obtain extremely long follow-up
      data. Results: 30/43 patients had MP and 13/43 had SE. Follow-up was obtained in
      83% MP and 70% SE patients. 60% of MP and 78% of SE patients reported regular
      evacuations and no soiling. 20% MP patients had occasional urgency or soiling or
      episodic constipation. 12% MP and 22% SE patients required antegrade continence
      enemas (ACE) or scheduled cathartics and/or stool softeners. 4% MP had no
      appreciable benefit, frequent loose stools and soiling, presumably from
      encopresis. Conclusion: MR is characterized by diminished sensation, poor
      compliance and defective contractility. Patients with MR do better with MP, which
      effectively removes the entire rectum versus SE, where normal caliber colon is
      anastomosed to MR at the peritoneal reflection; furthermore, MP reliably
      preserves continence; whereas total proctectomy (trans-anal or trans-abdominal)
      may cause incontinence.

PMID- 29326817
TI  - Seating in aged care: Physical fit, independence and comfort.
AB  - Objectives: This research was intended to provide a greater understanding of the
      context and needs of aged care seating, specifically:To conduct an audit of
      typical chairs used in aged care facilities;To collect data about resident and
      staff experiences and behaviour around chairs in order to gain a deeper
      understanding of the exact issues that residents and staff have with the chairs
      they use at aged care facilities;To identify positive and negative issues
      influencing use of chairs in aged care facilities;To deliver evidence-based
      recommendations for the design of chairs for aged care facilities. Methods:
      Methods included a chair dimension audit, interviews with residents, experts and
      carers and observations of aged care residents getting into chairs, sitting in
      them and getting out. Results: Results showed that residents, experts and carers
      all prefer chairs which are above the recommended height for older people so that
      they will be able to get out of them more easily. Armrests were essential for
      ease of entry and egress. However, many residents struggled with chairs which
      were also too deep in the seat pan so that they could not easily touch the floor
      or sit comfortably and were forced to slump. Most residents used cushions and
      pillows to relieve discomfort where possible. Conclusion: The implications of
      these issues for chair design and selection are discussed. Variable height
      chairs, a range of chairs of different heights in each space and footrests could
      all address the height problem. Chair designers need to address the seat depth
      problem by reducing depth in most aged care specific chairs, even when they are
      higher. Armrests must be provided but could be made easier to grip. Addressing
      these issues would increase access to comfortable yet easy-to-use chairs for a
      wider range of the aged care population.

PMID- 29326814
TI  - Paediatric dentistry- novel evolvement.
AB  - Pediatric dentistry provides primary and comprehensive preventive and therapeutic
      oral health care for infants and children through adolescence, together with
      special health care needs. This specialty encompasses a variety of skills,
      disciplines, procedures and techniques that share a common origin with other
      dental specialties however these have been modified and reformed to the
      distinctive requirements of infants, children, adolescents and special health
      care needs. Disciplines comprise of behavior guidance, care of the medically and
      developmentally compromised and disabled patient, supervision of orofacial growth
      and development, caries prevention, sedation, pharmacological management, and
      hospital dentistry including other traditional fields of dentistry. The skills
      apply to the ever-changing stages of dental, physical, and psychosocial
      development for treating conditions and diseases distinctive to growing
      individuals. Hence with the changing scope of practice it is imperative that the
      clinician stays updated with the current evidence based trends in practice,
      collaborates with other disciplines and Imparts quality oral health care tailored
      to the specific needs of every child.

PMID- 29326816
TI  - Immune checkpoint inhibition: prospects for prevention and therapy of
      hepatocellular carcinoma.
AB  - The global prevalence of liver cancer is rapidly rising, mostly as a result of
      the amplified incidence rates of viral hepatitis, alcohol abuse and obesity in
      recent decades. Treatment options for liver cancer are remarkably limited with
      sorafenib being the gold standard for advanced, unresectable hepatocellular
      carcinoma but offering extremely limited improvement of survival time. The immune
      system is now recognised as a key regulator of cancer development through its
      ability to protect against infection and chronic inflammation, which promote
      cancer development, and eliminate tumour cells when present. However, the
      tolerogenic nature of the liver means that the immune response to infection,
      chronic inflammation and tumour cells within the hepatic environment is usually
      ineffective. Here we review the roles that immune cells and cytokines have in the
      development of the most common primary liver cancer, hepatocellular carcinoma
      (HCC). We then examine how the immune system may be subverted throughout the
      stages of HCC development, particularly with respect to immune inhibitory
      molecules, also known as immune checkpoints, such as programmed cell death
      protein-1, programmed cell death 1 ligand 1 and cytotoxic T lymphocyte antigen 4,
      which have become therapeutic targets. Finally, we assess preclinical and
      clinical studies where immune checkpoint inhibitors have been used to modify
      disease during the carcinogenic process. In conclusion, inhibitory molecule-based
      immunotherapy for HCC is in its infancy and further detailed research in relevant
      in vivo models is required before its full potential can be realised.

PMID- 29326818
TI  - Coping, social support and information in patients with pulmonary arterial
      hypertension or chronic thromboembolic pulmonary hypertension: A 2-year
      retrospective cohort study.
AB  - Objectives: Pulmonary arterial hypertension and chronic thromboembolic pulmonary
      hypertension are severe diseases with complicated treatment that need care at
      specialist clinics. The aim was to investigate changes in the patients'
      perceptions on coping, social support and received information when attending a
      newly started nurse-coordinated pulmonary arterial hypertension-outpatient
      clinic. Methods: The present study was a descriptive, questionnaire-based cohort
      study including 42 adult patients. To evaluate coping, the Pearlin Mastery Scale
      was used. Social support, information and health-related quality of life were
      measured using Social Network and Support Scale, QLQ-INFO25 and the EQ-5D.
      Results: Attending the pulmonary arterial hypertension-outpatient clinic
      increased coping ability (Mastery Scale) significantly (baseline 16.0 +/- 3.3
      points vs 2-year follow-up 19.6 +/- 5.2 points, p < 0.001) while there was no
      difference in social network and support or in perception of received information
      after. Patients who improved their coping ability (67%) were younger, had better
      exercise capacity, experienced better health-related quality of life and were
      more satisfied with received information about treatment and medical tests than
      those who reduced the coping ability. There was no difference in gender,
      diagnosis, time since diagnose, pulmonary arterial hypertension-specific
      treatment, education level or civil status between the two groups. Conclusion:
      This study suggests that the pulmonary arterial hypertension-team, in partnership
      with the patient, can support patients to take control of their disease and
      increase their health-related quality of life.

PMID- 29326819
TI  - Association between bullying and pediatric psychiatric hospitalizations.
AB  - Objectives: Bullying is a serious public health issue. We sought to demonstrate
      an association between bullying victimization and hospital admissions for acute
      psychiatric problems. We described the demographics and types of bullying in a
      sample of hospitalized patients in Staten Island, NY, and compared bullying
      victimization scores with psychiatric versus medical admissions. Methods:
      Patients in grades 3-12 were recruited from the Staten Island University Hospital
      Inpatient Pediatrics unit and emergency department. Patients completed the
      validated Olweus Bully/Victim Questionnaire (OBQ) was analyzed to formulate a
      report of bullying in our sample as well as a sub-score measurement of bullying
      victimization. Pediatric residents simultaneously documented whether the subject
      was a medical versus an in-patient psychiatry admission. Statistical analysis was
      performed to look for an association between the victimization sub-score and a
      psychiatric indication for admission. Results: A total of 185 surveys were
      analyzed. Peak bullying occurred in 7th and 8th grades. Demographics and types of
      bullying in our sample were described. A strong association between bullying
      victimization and hospitalization for in-patient psychiatry was demonstrated.
      Association between bullying victimization and suicidal ideation, psychiatry, and
      social work consults was also shown. Concern for an association between
      hospitalization for psychogenic illness and bullying victimization was also
      raised. Conclusions: There is a significant association between bullying
      victimization and psychiatric hospital admissions. This raises the specter of the
      serious consequences of bullying as it is the first study to prospectively link
      hospital admissions to bullying. Studies using a valid measure of psychogenic
      illness to look for an association with bullying victimization are needed.

PMID- 29326820
TI  - A case of intra-arterial thrombolysis with alteplase in a patient with hypothenar
      hammer syndrome but without underlying aneurysm.
AB  - Hypothenar hammer syndrome is a cause of symptomatic ischemia of the hand
      secondary to the formation of aneurysm or thrombosis of the ulnar artery in the
      setting of a complete or incomplete palmar arch. Acute occlusive thrombus or
      embolus of the hand represents a complex problem that often may require immediate
      surgical intervention. We report a case of acute unilateral arterial hand
      ischemia requiring catheter-directed thrombolysis with Alteplase therapy in a
      patient with acute occlusive arterial thrombosis of the left ulnar artery. A
      catheter-directed thrombolytic regimen consisted of Alteplase 1 mg/h for 24 h,
      and heparin was infused through the sheath side arm at a rate of 500 units per
      hour for resolution of the thrombus and improvement in symptoms. A former truck
      driver presented with worsening pain and subsequent development of significant
      cyanosis with early gangrenous changes of the left second and third fingertips.
      He had significant callous of the hypothenar eminence and reported that his left
      hand was not only his "driving" hand but also a cane has been used in his left
      hand to ambulate. Initial angiogram revealed only ulnar artery occlusion at the
      wrist with reconstitution just distal to the hypothenar eminence. After 24 h of
      the initiation of thrombolysis, repeat angiography revealed resolution with a
      widely patent ulnar artery. His symptoms and the color of his digits immediately
      improved, and within a few months, his hand had normalized. The patient had no
      clinical sequelae of thrombolytic therapy. Catheter-directed thrombolytic therapy
      in situations of acute occlusive thrombus of the hand may provide a therapeutic
      option for patients with suspected hypothenar hammer syndrome. However,
      thrombolytic therapy carries risk of significant hemorrhagic complications.
      Before initiating therapy, careful judgment about the possibility for bleeding
      risk is required. This provides for a minimally invasive alternative to open
      surgical revascularization especially in the absence of underlying correctable
      anatomic defect such as aneurysm.

PMID- 29326821
TI  - Age, Sex, and Gene Expression Score identifies a symptomatic, nondiabetic male
      patient as being at high risk of obstructive coronary artery disease.
AB  - In October 2015, a 74-year-old Caucasian male patient (past medical history of
      hyperlipidemia, paroxysmal atrial fibrillation, hypertension, and hypothyroidism)
      presented to the cardiologist for follow-up outpatient evaluation of exertional
      chest pain. The patient had recently been seen at the Emergency Department for
      the same complaint. At that time, the patient's cardiac markers, EKG, and
      pharmacological nuclear stress testing were all reported as normal. At
      presentation to the cardiologist, the patient's physical examination findings
      were unremarkable. Over the course of the following year, repeat
      electrocardiograms and myocardial perfusion imaging studies demonstrated no
      evidence of ischemia. Despite the persistence of symptoms, the patient was
      reluctant to undergo invasive testing. The cardiologist ordered a simple blood
      test: the Age, Sex, and Gene Expression Score, which provides the current
      likelihood of obstructive coronary artery disease in nondiabetic patients. Based
      on the high Age, Sex, and Gene Expression Score result, the patient underwent
      invasive coronary angiography and a 98% stenotic lesion in the proximal left
      anterior descending artery was discovered. A drug-eluting coronary stent was
      placed and resulted in the complete resolution of the patient's symptoms.

PMID- 29326822
TI  - Acute myeloid leukemia with KMT2A-SEPT5 translocation: A case report and review
      of the literature.
AB  - Chromosomal rearrangement involving the KMT2A gene is one of the most common
      genetic alteration in acute myeloid leukemia. A total of 135 different KMT2A
      rearrangements have been identified, where 94 translocation partner genes are now
      characterized at the molecular level. Of these 94 translocation partner genes, 35
      translocation partner genes occur recurrently, but only 9 specific gene fusions
      account for more than 90% of cases. Translocation of KMT2A with SEPT5 gene at
      22q11.2 is rare, with few reported cases in the literature. In this report, we
      are presenting a case of KMT2A-SEPT5 fusion in de novo acute myeloid leukemia
      with t(11;22)(q23;q11.2) with a review of the literature.

PMID- 29326823
TI  - Lichen planus following tetanus-diphtheria-acellular pertussis vaccination: A
      case report and review of the literature.
AB  - Lichen planus is an inflammatory dermatosis with a prevalence of approximately
      1%. Recent meta-analyses show that patients with hepatitis C virus have a 2.5- to
      4.5-fold increased risk of developing lichen planus. Lichen planus has also
      followed vaccinations and has specifically been attributed to the hepatitis B
      vaccine, the influenza vaccine, and the tetanus-diphtheria-acellular pertussis
      vaccine. We describe a case of lichen planus in a hepatitis C virus-infected
      African American male occurring in temporal association with the administration
      of the tetanus-diphtheria-acellular pertussis vaccine. The patient's presentation
      was clinically consistent with lichen planus and confirmed by biopsy. It is
      likely that many cases of vaccine-induced lichen planus have gone unpublished or
      unrecognized. In areas with high prevalence of hepatitis C virus infection, we
      may expect to see more cases of vaccine-induced lichen planus especially in light
      of the updated Centers for Disease Control and Prevention tetanus-diphtheria
      acellular pertussis vaccination recommendations. This case serves to educate
      healthcare providers about vaccine-induced lichen planus and, in particular, the
      need to counsel hepatitis C virus-infected patients about a potential risk of
      developing lichen planus following vaccination. We also reflect on current
      theories suggesting the T-cell-mediated pathogenesis of lichen planus and the
      role that hepatitis C virus and toxoid or protein vaccines may play in initiating
      the disease.

PMID- 29326824
TI  - Secondary multifocal intraocular lens implantation: A novel management strategy
      for white cataracts.
AB  - Objectives: This study was designed to analyse the outcomes of secondary
      multifocal intraocular lens implantation in eyes with white cataracts. Methods:
      White cataract patients undergoing secondary multifocal intraocular lens
      implantation between June 2014 and January 2015 were evaluated prospectively. As
      opposed to a conventional primary intraocular lens implantation for an optimal
      patient, the white cataract was first extracted, followed by optical biometry
      measurements. Whether or not the patient had adequate visual acuity was
      identified, and the multifocal intraocular lens was implanted secondarily. A
      total of five appropriate white cataract patients were enrolled in this secondary
      multifocal intraocular lens implantation study and were retrospectively reviewed.
      Results: All five secondary implantations of the multifocal intraocular lenses
      were successful, without obvious adverse events. The uncorrected near visual
      acuity LogMAR was 0.4-0.5, and the distance visual acuity was -0.1 to 0.1 after
      12 months of the multifocal intraocular lens implantation. All patients achieved
      satisfactory near and distance visual acuities and spectacle freedom. Conclusion:
      Two-stage multifocal intraocular lens implantation is a safe and novel technique
      for the management of white cataract patients to optimise near and distance
      visual acuities.

PMID- 29326825
TI  - Staphylococcal scalded skin syndrome: A pediatric dermatology case report.
AB  - Staphylococcal scalded skin syndrome is a condition which predominantly affects
      children and causes a spectrum of skin lesions. We present a case of a 2-month
      old infant with complaints of fever and fragile blisters over the body. The
      mucosal areas were spared. The diagnosis of staphylococcal scalded skin syndrome
      was reached on clinical grounds and culture report. The patient responded well to
      the treatment, which included an antibiotic (cloxacillin), an analgesic
      (paracetamol), and hydration with intravenous fluids. He was discharged after 8
      days, with almost complete resolution of his skin lesions. Having a high clinical
      suspicion for staphylococcal scalded skin syndrome, early diagnosis/treatment,
      and following robust hygiene measures are imperative for the effective management
      of staphylococcal scalded skin syndrome. More efforts are needed to develop novel
      therapies for staphylococcal scalded skin syndrome.

PMID- 29326826
TI  - Collision tumor consisting of a colorectal adenocarcinoma and dissemination of a
      gastric adenocarcinoma.
AB  - Background: Collision tumors, composed of histologically distinct tumor types,
      are rare entities, especially in the colorectum, and corresponding evidence-based
      clinical management or treatment strategies are poorly defined. This is the first
      report of a collision tumor composed of two histologically distinct
      adenocarcinomas. Case presentation: A 78-year-old male showed severe anemia and a
      10% body weight loss over 1 month. Preoperative examination revealed T3N1M0 stage
      IIIA gastric cancer and T3N0M0 stage IIA rectal cancer. Distal gastrectomy and
      rectectomy with regional lymph node dissection were performed.
      Immunohistochemistry revealed two distinct adenocarcinomas with gland duct
      structures - a colorectal adenocarcinoma and a disseminated gastric
      adenocarcinoma - that had collided to form an invasive tumor on the serosal
      surface of the anterior rectum wall. Conclusion: This extremely rare case of a
      collision tumor supports that precise immunohistochemical identification of all
      tumor components is needed for guiding decisions affecting overall prognosis,
      adjuvant treatment and survival.

PMID- 29326827
TI  - Premature Ventricular Contraction-induced Cardiomyopathy.
AB  - Premature ventricular contractions (PVCs) are very common and usually do not
      require treatment. However, in the clinical setting of troublesome symptoms, or
      when PVCs trigger polymorphic ventricular tachycardia or cause cardiomyopathy,
      proper treatment is critical. In this review, the clinical syndrome of PVC
      induced cardiomyopathy, including risk factors for development and treatment, is
      discussed. Although PVC-induced cardiomyopathy is typically associated with
      frequent PVCs there are also patients with this burden that do not develop
      cardiomyopathy, suggesting a differential susceptibility. Treatment often
      consists of catheter ablation, although antiarrhythmic medications may also
      provide both reduction in PVC frequency and resolution of left ventricular
      dysfunction.

PMID- 29326828
TI  - Cryoballoon Ablation in Today's Practice: Can the Left Common Ostium Be Ablated
      and Injury to the Right Phrenic Nerve Avoided?
AB  - Cryoballoon ablation is rapidly gaining popularity among electrophysiologists in
      the setting of pulmonary vein isolation for the treatment of AF. The first part
      of the following review focuses on the feasibility and clinical outcome of this
      technique in patients exhibiting a left common ostium. In the second part, we
      discuss how to predict and prevent the most common complication related to
      cryoballoon ablation: right phrenic nerve palsy.

PMID- 29326829
TI  - Choice of Ventricular Pacing Site: the End of Non-physiological, Apical
      Ventricular Pacing?

PMID- 29326830
TI  - Optimum Risk Assessment for Stroke in Atrial Fibrillation: Should We Hold the
      Status Quo or Consider Magnitude Synergism and Left Atrial Appendage Anatomy?
AB  - Thromboembolic stroke and systemic embolism are generally agreed to be the major
      morbidity/mortality concerns for patients with AF. However, the risk of
      thromboembolism is not the same for all AF patients. Both AF and comorbidities
      must interact synergistically to create the risk for thromboembolism. But, is the
      synergism dichotomous - AF present or absent, comorbid disorder present or absent
      - or does synergism have magnitude, depending on the number and severity of the
      associated disorders and the amount of time one is in AF? This review discusses
      the current risk-score contributors and options for assessing risk of
      thromboembolism in AF patients, and what their combined roles might be. Also
      covered is the consideration of left atrial appendage anatomy in this context.

PMID- 29326831
TI  - Management of Complications in Anticoagulated Patients with Atrial Fibrillation.
AB  - Oral anticoagulation is mandatory for patients at high risk of thromboembolism,
      but the risk of bleeding should also be taken into account. Direct oral
      anticoagulants are now recommended for non-valvular AF as a potential alternative
      to warfarin. In this article we discuss methods to assess the anticoagulant
      effect of these agents, specific and general antidotes, and management of
      complications such as embolic and haemorrhagic stroke, and significant bleeding.

PMID- 29326832
TI  - At the Atrioventricular Crossroads: Dual Pathway Electrophysiology in the
      Atrioventricular Node and its Underlying Heterogeneities.
AB  - The atrioventricular node (AVN) is a complex structure that performs a variety of
      functions in the heart. The AVN is primarily an electrical gatekeeper between the
      atria and ventricles and introduces a delay between atrial and ventricular
      excitation, allowing for efficient ventricular filling. The AVN is composed of
      several compartments that safely transmit electrical excitation from the atria to
      the ventricles via the fast or slow pathways. There are many electrophysiological
      differences between these pathways, including conduction time and electrical
      refractoriness, that increase the predisposition of the atrioventricular junction
      to arrhythmias such as atrioventricular nodal re-entrant tachycardia. These
      varied electrophysiological characteristics of the fast and slow pathways stem
      from their unique structural and molecular composition (tissue and cellular
      geometry, ion channels and gap junctions). This review summarises the structural
      and molecular heterogeneities of the human AVN and how they result in
      electrophysiological variations and arrhythmias.

PMID- 29326833
TI  - Ganglionated Plexi Ablation: Physiology and Clinical Applications.
AB  - Ganglionated plexi (GP), consisting of conglomerations of autonomic ganglia on
      the epicardial surface of the heart, have been shown to play a significant role
      in different arrhythmias, including atrial fibrillation. GP ablation has become
      an adjunctive procedure in the treatment of atrial fibrillation, while it has
      been used successfully in preliminary studies in vasovagal syncope. This review
      will present the current data on the physiology and clinical applications of GP
      ablation in the treatment of atrial fibrillation and other diseases.

PMID- 29326834
TI  - Ablation of Atrial Fibrillation in Patients with Congenital Heart Disease.
AB  - With improved surgical techniques and medical management for patients with
      congenital heart diseases, more patients are living longer and well into
      adulthood. This improved survival comes with a price of increased morbidity,
      mainly secondary to increased risk of tachyarrhythmias. One of the major
      arrhythmias commonly encountered in this subset of cardiac patients is AF.
      Similar to the general population, the risk of AF increases with advancing age,
      and is mainly secondary to the abnormal anatomy, abnormal pressure and volume
      parameters in the hearts of these patients and to the increased scarring and
      inflammation seen in the left atrium following multiple surgical procedures.
      Catheter ablation for AF has been shown to be a very effective treatment modality
      in patients with refractory AF. However, data and guidelines regarding catheter
      ablation in patients with congenital heart disease are not well established. This
      review will shed light on the procedural techniques, success rates and
      complications of AF catheter ablation in patients with different types of CHD,
      including atrial septal defects, tetralogy of Fallot, persistent left superior
      vena cava, heterotaxy syndrome and atrial isomerism, and Ebstein anomaly.

PMID- 29326835
TI  - Ablation of Atrial Fibrillation Drivers.
AB  - Pulmonary vein isolation (PVI) is central to ablation approaches for atrial
      fibrillation (AF), yet many patients still have arrhythmia recurrence after one
      or more procedures, despite evolving technologies for PVI. Ablation of localised
      AF drivers, which lie outside the pulmonary veins in many patients, is a
      practical approach that has been shown to improve success by many groups. Such
      localised drivers lie in atrial regions shown mechanistically to sustain AF in
      optical mapping and clinical studies of human AF, as well as computational and
      animal studies. Clinical studies now verify rotational activation by multiple
      mapping approaches in the same patients, at sites where ablation terminates
      persistent AF. This review article provides a mechanistic and clinical rationale
      to ablate localised drivers, and describes successful techniques for their
      ablation as well as pitfalls to avoid, which may explain discrepancies between
      results from some centres. We hope that this review will serve as a platform for
      future improvements in the patient-tailored ablation for complex arrhythmias.

PMID- 29326836
TI  - Minimally Invasive Epicardial Surgical Ablation Alone Versus Hybrid Ablation for
      Atrial Fibrillation: A Systematic Review and Meta-Analysis.
AB  - Maintaining sinus rhythm in patients with non-paroxysmal AF is an elusive goal.
      Some suggest that hybrid ablation, combining minimally invasive epicardial
      surgical ablation with endocardial catheter ablation, may be more effective than
      either modality alone. However, randomised trials are lacking. We investigated
      whether hybrid ablation is more effective than epicardial ablation alone at
      preventing recurrent AF by performing a systematic review and meta-analysis. The
      review was prospectively registered with PROSPERO (CRD42016043389). MEDLINE and
      EMBASE were searched for studies of standalone minimally invasive epicardial
      ablation of AF and/or hybrid ablation, identifying 41 non-overlapping studies
      comprising 2737 patients. A random-effects meta-analysis, meta-regression and
      sensitivity analysis were performed. Single-procedure survival free from atrial
      arrhythmias without antiarrhythmic drugs was similar between epicardial-alone and
      hybrid approaches at 12 months (epicardial alone 71.5 %; [95 % CI 66.1-76.9],
      hybrid 63.2 %; [95 % CI 51.5-75.0]) and 24 months (epicardial alone 68.5 %; [95 %
      CI 57.7-79.3], hybrid 57.0 %; [95 % CI 33.6-80.4]). Freedom from atrial
      arrhythmias with AADs and rates of unplanned additional catheter ablations were
      also similar between groups. Major complications occurred more often with hybrid
      ablation (epicardial alone 2.9 %; [95 % CI 1.9-3.9], hybrid 7.3 %; [95 % CI 4.2
      10.5]). Meta-regression suggested that bipolar radiofrequency energy and
      thoracoscopic access were associated with greater efficacy, but adjusting for
      these factors did not unmask any difference between epicardial-alone and hybrid
      ablation. Hybrid and epicardial ablation alone appear to be equally effective
      treatments for AF, although hybrid ablation may be associated with higher
      complication rates. These data derived from observational studies should be
      verified with randomised data.

PMID- 29326837
TI  - One-stage Approach for Hybrid Atrial Fibrillation Treatment.
AB  - The one-stage approach for hybrid atrial fibrillation involves the simultaneous
      and close cooperation of different medical specialties. This review attempts to
      describe its challenging issues, exposing a plan to balance thrombotic risk and
      bleeding risk. It describes the combined surgical-electrophysiological procedure.
      Specific topics, involving hemodynamic, fluid and respiratory management during
      surgery are considered, and problems related to postoperative pain are surveyed.

PMID- 29326838
TI  - Increasing the Single-Procedure Success Rate of Pulmonary Vein Isolation.
AB  - To improve the single-procedural success and long-term outcomes of catheter
      ablation techniques for AF, there is a need for durable, contiguous and
      transmural lesions encircling the pulmonary veins (PV). Measurement of contact
      force (CF) between the catheter tip and the target tissue can optimise ablation
      procedures. A new approach to obtain single-procedure durable PV isolation (PVI)
      using the latest CF technology combined with the CARTO VISITAGTM Module with
      Ablation Index (Biosense Webster) has been shown in small studies to almost
      eliminate recurrence of paroxysmal AF at 1-year follow up and to make PVI
      procedures more reproducible. The use of a standardised workflow is expected to
      increase the reproducibility of results and to increase the efficiency of PVI
      procedures.

PMID- 29326839
TI  - Can We Select Patients for Prophylactic VT Ablation?

PMID- 29326840
TI  - Reproductive gene expression in a coral reef fish exposed to increasing
      temperature across generations.
AB  - Reproduction in marine fish is generally tightly linked with water temperature.
      Consequently, when adults are exposed to projected future ocean temperatures,
      reproductive output of many species declines precipitously. Recent research has
      shown that in the common reef fish, Acanthochromis polyacanthus, step-wise
      exposure to higher temperatures over two generations (parents: +1.5 degrees C,
      offspring: +3.0 degrees C) can improve reproductive output in the F2 generation
      compared to F2 fish that have experienced the same high temperatures over two
      generations (F1 parents: +3.0 degrees C, F2 offspring: +3.0 degrees C). To
      investigate how a step-wise increase in temperature between generations improved
      reproductive capacity, we tested the expression of well-known teleost
      reproductive genes in the brain and gonads of F2 fish using quantitative reverse
      transcription PCR and compared it among control (+0.0 degrees C for two
      generations), developmental (+3.0 degrees C in second generation only), step
      (+1.5 degrees C in first generation and +3.0 degrees C in second generation), and
      transgenerational (+3.0 degrees C for two generations) treatments. We found that
      levels of gonadotropin receptor gene expression (Fshr and Lhcgr) in the testes
      were reduced in developmental and transgenerational temperature treatments, but
      were similar to control levels in the step treatment. This suggests Fshr and
      Lhcgr may be involved in regulating male reproductive capacity in A.
      polyacanthus. In addition, lower Fshb expression in the brain of females in all
      temperature treatments compared to control, suggests that Fshb expression, which
      is involved in vitellogenesis, is sensitive to high temperatures. Our results
      help elucidate key genes that facilitate successful reproduction in reef fishes
      when they experience a gradual increase in temperature across generations
      consistent with the trajectory of climate change.

PMID- 29326841
TI  - It is not just menopause: symptom clustering in the Study of Women's Health
      Across the Nation.
AB  - Background: Patterns of symptom clustering in midlife women may suggest common
      underlying mechanisms or may identify women at risk of adverse health outcomes
      or, conversely, likely to experience healthy aging. This paper assesses symptom
      clustering in the Study of Women's Health Across the Nation (SWAN) longitudinally
      by stage of reproductive aging and estimates the probability of women
      experiencing specific symptom clusters. We also evaluate factors that influence
      the likelihood of specific symptom clusters and assess whether symptom clustering
      is associated with women's self-reported health status. Methods: This analysis
      includes 3289 participants in the multiethnic SWAN cohort who provided
      information on 58 symptoms reflecting a broad range of physical, psychological
      and menopausal symptoms at baseline and 7 follow-up visits over 16 years. We
      conducted latent transition analyses to assess symptom clustering and to model
      symptomatology across the menopausal transition (pre, early peri-, late peri- and
      post-menopausal). Joint multinomial logistic regression models were used to
      identify demographic characteristics associated with premenopausal latent class
      membership. A partial proportional odds regression model was used to assess the
      association between latent class membership and self-reported health status.
      Results: We identified six latent classes that ranged from highly symptomatic
      (LC1) across most measured symptoms, to moderately symptomatic across most
      measured symptoms (LC2), to moderately symptomatic for a subset of symptoms
      (vasomotor symptoms, pain, fatigue, sleep disturbances and physical health
      symptoms) (LC3 and LC5) with one class (LC3) including interference in life
      activities because of physical health symptoms, to numerous milder symptoms,
      dominated by fatigue and psychological symptoms (LC4), to relatively asymptomatic
      (LC6). In pre-menopause, 10% of women were classified in LC1, 16% in LC2, 14% in
      LC3 and LC4, 26% in LC5, and 20% in LC6. Intensity of vasomotor and urogenital
      symptoms as well as sexual desire) differed minimally by latent class.
      Classification into the two most symptomatic classes was strongly associated with
      financial strain, White race/ethnicity, obesity and smoking status. Over time,
      women were most likely to remain within the same latent class as they
      transitioned through menopause stages (range 39-76%), although some women
      worsened or improved. The probability of moving between classes did not differ
      substantially by menopausal stage. Women in the highly symptomatic classes more
      frequently rated their health as fair to poor compared to women in the least
      symptomatic class. Conclusion: Clear patterns of symptom clustering were present
      early in midlife, tended to be stable over time, and were strongly associated
      with self-perceived health. Notably, vasomotor symptoms tended to cluster with
      sleep disturbances and fatigue, were present in each of the moderate to highly
      symptomatic classes, but were not a defining characteristic of the symptom
      clusters. Clustering of midlife women by symptoms may suggest common underlying
      mechanisms amenable to interventions. Given that one-quarter of midlife women
      were highly or moderately symptomatic across all domains in the pre-menopause,
      addressing symptom burden in early midlife is likely critical to ameliorating
      risk in the most vulnerable populations.

PMID- 29326842
TI  - Barriers to Peritoneal Dialysis in Aboriginal Patients.
AB  - Background: Aboriginal people in Canada have an unduly high burden of end-stage
      kidney disease (ESKD) and many live in rural settings. Peritoneal dialysis (PD)
      is a home-based dialysis modality that may provide a valuable alternative to in
      center hemodialysis which is relatively underutilized by the Aboriginal
      population. Objective: We aim to assess the barriers to PD utilization in
      Aboriginal patients with ESKD. Design: This article is a prospective
      observational cohort study. Setting: The setting involves 3 predialysis clinics
      in Winnipeg, Kingston, and Moose Factory. Patients: The patients were 99
      individuals (67 non-Aboriginal and 32 Aboriginal) who were at least 18 years of
      age with an estimated glomerular filtration rate of less than 30 mL/min/1.73m2,
      and were enrolled in one of the 3 study sites from April 2011 to October 2013.
      Measurements: Patient demographics and comorbidities were documented. Barriers to
      PD, PD as modality choice, and Aboriginal status were assessed via patient survey
      upon study enrollment. PD use as the initial dialysis modality was assessed via
      monthly patient follow-up for 1 year after enrollment in the study. Methods: The
      patient survey was created based on literature review of known barriers to PD,
      repaired based on direct patient feedback, and tested for reliability via the
      test-retest method. Differences in PD choice, barriers to PD, and PD use between
      Aboriginal and non-Aboriginal patients were determined by chi-square test and
      logistic regression. Results: All patients enrolled in the study completed the
      survey. Mean age was 65.5 versus 54.6 years for non-Aboriginals and Aboriginals,
      respectively. Barriers to PD significantly associated with Aboriginal status were
      lack of money (odds ratio [OR]: 21.3; 95% confidence interval [CI]: 5.3-86.4; P <
      .0001) and anxiety (OR: 2.8; 95% CI: 1.1-7.1; P = .03). There was no difference
      in PD choice between non-Aboriginals and Aboriginals (66.7% vs 68.8%,
      respectively; P = .83). One of 67 non-Aboriginals (1.5%) and 5 of 32 Aboriginals
      (15.6%) died prior to initiating dialysis (P = .013). No significant difference
      was observed between non-Aboriginals (33%) and Aboriginals (28%) in use of PD (P
      = .81). Limitations: Small sample size was a limitation of this study.
      Conclusions: Aboriginal people in Canada have a disproportionately large burden
      of ESKD, and PD could provide an alternative to in-center hemodialysis for those
      living in rural areas. Our study identified anxiety and lack of money as barriers
      to PD significantly associated with Aboriginal status. When choosing dialysis
      modality, shared decision making between physicians and patient is of key
      importance to weigh all potential benefits and risks and emphasize the Aboriginal
      patient's values and preferences. These results can be used to guide future
      research and to help devise interventions targeting barriers to PD in
      Aboriginals.

PMID- 29326843
TI  - Risk of Acute Kidney Injury in Patients Randomized to a Restrictive Versus
      Liberal Approach to Red Blood Cell Transfusion in Cardiac Surgery: A Substudy
      Protocol of the Transfusion Requirements in Cardiac Surgery III Noninferiority
      Trial.
AB  - Background: When safe to do so, avoiding blood transfusions in cardiac surgery
      can avoid the risk of transfusion-related infections and other complications
      while protecting a scarce resource and reducing costs. This protocol describes a
      kidney substudy of the Transfusion Requirements in Cardiac Surgery III (TRICS
      III) trial, a multinational noninferiority randomized controlled trial to
      determine whether the risk of major clinical outcomes in patients undergoing
      planned cardiac surgery with cardiopulmonary bypass is no greater with a
      restrictive versus liberal approach to red blood cell transfusion. Objective: The
      objective of this substudy is to determine whether the risk of acute kidney
      injury is no greater with a restrictive versus liberal approach to red blood cell
      transfusion, and whether this holds true in patients with and without preexisting
      chronic kidney disease. Design and Setting: Multinational noninferiority
      randomized controlled trial conducted in 73 centers in 19 countries (2014-2017).
      Patients: Patients (~4800) undergoing planned cardiac surgery with
      cardiopulmonary bypass. Measurements: The primary outcome of this substudy is
      perioperative acute kidney injury, defined as an acute rise in serum creatinine
      from the preoperative value (obtained in the 30-day period before surgery), where
      an acute rise is defined as >=26.5 MUmol/L in the first 48 hours after surgery or
      >=50% in the first 7 days after surgery. Methods: We will report the absolute
      risk difference in acute kidney injury and the 95% confidence interval. We will
      repeat the primary analysis using alternative definitions of acute kidney injury,
      including staging definitions, and will examine effect modification by
      preexisting chronic kidney disease (defined as a preoperative estimated
      glomerular filtration rate [eGFR] <60 mL/min/1.73 m2). Limitations: It is not
      possible to blind patients or providers to the intervention; however, objective
      measures will be used to assess outcomes, and outcome assessors will be blinded
      to the intervention assignment. Results: Substudy results will be reported by the
      year 2018. Conclusions: This substudy will provide generalizable estimates of the
      risk of acute kidney injury of a restrictive versus liberal approach to red blood
      cell transfusion in the presence of anemia during cardiac surgery done with
      cardiopulmonary bypass. Trial Registration: www.clinicaltrials.gov; clinical
      trial registration number NCT 02042898.

PMID- 29326845
TI  - Tuberculosis Test Usage and Medical Expenditures from Outpatient Insurance Claims
      Data, 2013.
AB  - Objective: To evaluate TB test usage and associated direct medical expenditures
      from 2013 private insurance claims data in the United States (US). Methods: We
      extracted outpatient claims for TB-specific and nonspecific tests from the 2013
      MarketScan(r) commercial database. We estimated average expenditures (adjusted
      for claim and patient characteristics) using semilog regression analyses and
      compared them to the Centers for Medicare and Medicaid Services (CMS) national
      reimbursement limits. Results: Among the TB-specific tests, 1.4% of the enrollees
      had at least one claim, of which the tuberculin skin test was most common (86%)
      and least expensive ($9). The T-SPOT(r) was the most expensive among the TB
      specific tests ($106). Among nonspecific TB tests, the chest radiograph was the
      most used test (78%), while chest computerized tomography was the most expensive
      ($251). Adjusted average expenditures for the majority of tests (~74%) were above
      CMS limits. We estimated that total United States medical expenditures for the
      employer-based privately insured population for TB-specific tests were $53.0
      million in 2013, of which enrollees paid 17% ($9 million). Conclusions: We found
      substantial differences in TB test usage and expenditures. Additionally, employer
      based private insurers and enrollees paid more than CMS limits for most TB tests.

PMID- 29326846
TI  - The Protective Effect of Sesamol in the Selenite-induced Experimental Cataract
      Model.
AB  - Objectives: To investigate the potential protective effects of sesamol in an
      experimental cataract model. Materials and Methods: Twenty-one Spraque Dawley rat
      pups were randomly assigned into three groups, seven rats in each. All the rats
      except for those in the control group were injected subcutaneously with a single
      dose of sodium selenite on postpartum day 9. On days 10-14, rats in the sham
      group were intraperitoneally administered 50 mg/kg/day saline solution, while
      rats in the sesamol group were given 50 mg/kg/day sesamol by the same route.
      Following cataract grading, the lenses and capsules were extracted and the mean
      levels of reduced glutathione (GSH), malondialdehyde (MDA), total antioxidant
      status (TAS) and total oxidant status (TOS) in lens supernatants were
      biochemically analyzed. Results: The control group did not show any development
      of cataract. It was found that the mean cataract grade in the sesamol group was
      significantly lower than that of the sham group (p<0.05). The mean GSH level and
      TAS in the sesamol group were significantly higher than those of the sham group
      while the mean TOS and MDA level in the sesamol group were significantly lower
      than those of the sham group (p<0.05). Conclusion: Our study shows that sesamol
      reduces TOS and MDA level and increases TAS and GSH level in the lens and
      inhibits cataract formation.

PMID- 29326847
TI  - Corneal, Scleral, Choroidal, and Foveal Thickness in Patients with Rheumatoid
      Arthritis.
AB  - Objectives: To investigate corneal, scleral, choroidal, and foveal thicknesses in
      female patients with rheumatoid arthritis (RA) and compare them with healthy
      subjects. Materials and Methods: This prospective study included consecutive
      female patients diagnosed with RA and healthy subjects. Corneal, scleral,
      choroidal, and retinal (foveal) thicknesses were obtained by using optical
      coherence tomography and a comparison was performed between groups for all
      outcome measures. Results: Thirty-six eyes of 36 female patients diagnosed with
      RA (group 1) and 36 eyes of 36 healthy female volunteers (group 2) were included.
      Mean corneal, scleral, choroidal thicknesses and retinal thickness at the fovea
      of group 1 were 543.3+/-33.7 um, 343.7+/-42.2 um, 214.6+/-50, and 213.5+/-18.9
      um, respectively; in group 2, these values were 549.9+/-29.6 MUm, 420.9+/-42.4
      MUm, 206.4+/-41.9 MUm, and 222+/-15.5 MUm, respectively. The comparison between
      group 1 and 2 with respect to corneal, choroidal, and foveal thicknesses did not
      reveal statistical significant differences (p>0.05). On the contrary, there was a
      statistically significant difference with respect to scleral thickness between
      the groups, with the RA patients demonstrating a thinner scleral layer (p<0.001).
      Conclusion: Female patients with RA seem to demonstrate statistically significant
      scleral thinning when compared with healthy subjects, while there was no
      difference concerning corneal, choroidal, and foveal thickness.

PMID- 29326844
TI  - Biology of premature ageing in survivors of cancer.
AB  - Over 30 million cancer survivors exist worldwide. Survivors have an earlier onset
      and higher incidence of chronic comorbidities, including endocrinopathies,
      cardiac dysfunction, osteoporosis, pulmonary fibrosis, secondary cancers and
      frailty than the general population; however, the fundamental basis of these
      changes at the cellular level is unknown. An electronic search was performed on
      Embase, Medline In-Process & Other Non-Indexed Citations, and the Cochrane
      Central Register of Controlled Trials. Original articles addressing the cellular
      biology of ageing and/or the mechanisms of cancer therapies similar to ageing
      mechanisms were included, and references of these articles were reviewed for
      further search. We found multiple biological process of ageing at the cellular
      level and their association with cancer therapies, as well as with clinical
      effects. The direct effects of various chemotherapies and radiation on telomere
      length, senescent cells, epigenetic modifications and microRNA were found. We
      review the effects of cancer therapies on recognised hallmarks of ageing. Long
      term comorbidities seen in cancer survivors mimic the phenotypes of ageing and
      likely result from the interaction between therapeutic exposures and the
      underlying biology of ageing. Long-term follow-up of cancer survivors and
      research on prevention strategies should be pursued to increase the length and
      quality of life among the growing population of cancer survivors.

PMID- 29326848
TI  - The Knowledge of Eye Physicians on Local Anesthetic Toxicity and Intravenous
      Lipid Treatment: Questionnaire Study.
AB  - Objectives: To evaluate the knowledge of ophthalmologists regarding local
      anesthesia toxicity syndrome (LATS) and intravenous lipid emulsion used in
      treatment, and to raise awareness of this issue. Materials and Methods: A
      questionnaire comprising 14 questions about demographics, local anesthesia (LA)
      use, toxicity, and treatment methods was administered to ophthalmologists at
      different hospitals. Results: The study included 104 ophthalmologists (25%
      residents, 67.3% specialists, 7.7% faculty members) with a mean age of 35.71+/
      6.53 years. The highest number of participants was from state hospitals (65.4%),
      and 34.6% of the physicians had been working in ophthalmology for more than 10
      years. Seventy-six percent of the participants reported using LA every day or
      more than twice a week, but 56.7% had received no specific training on this
      subject. No statistically significant difference was observed between different
      education levels and the rates of training (p=0.419). Bupivacaine was the most
      preferred LA and the majority of respondents (97.1%) did not use a test dose.
      Allergy (76%) and hypotension (68.3%) were the most common responses for early
      findings of LATS, while cardiac arrest (57.4%) and hepatotoxicity (56.4%) were
      given for late findings. The most common responses concerning the prevention of
      LATS included monitorization (72.4%) and use of appropriate doses (58.2%).
      Symptomatic treatment was selected by 72.4% of respondents and cardiopulmonary
      resuscitation and antihistamine treatment by 58.8%. Of the ophthalmologists in
      the study, 62.5% had never encountered LATS. The use of 20% intravenous lipid
      emulsion therapy for toxicity was known by 65% of the physicians, but only 1
      participant stated having used it previously. Conclusion: The importance of using
      20% lipid emulsion in LATS treatment and having it available where LA is
      administered must be emphasized, and there should be compulsory training programs
      for ophthalmologists on this subject.

PMID- 29326849
TI  - Spectral Domain Optical Coherence Tomography Findings in Carotid Artery Disease.
AB  - Objectives: To evaluate the effect of carotid artery disease on retinal
      morphology by means of spectral domain optical coherence tomography (SD-OCT).
      Materials and Methods: We examined 23 eyes with internal carotid artery (ICA)
      stenosis and 24 age- and gender-matched healthy eyes as a control group in this
      prospective, case-control study. Compherensive ophthalmic examination and SD-OCT
      scan were performed to all the patients. The average RNFL and macular thicknesses
      (MT) in the nine macular ETDRS areas were the major OCT measurements for our
      study. Results: Although all of the average RNFL and MT measurements were lower
      in the ICA stenosis group, only the total MT and outer ETDRS area
      (temporal/superior/nasal/inferior outer macula) values were found to be
      significantly thinner compared to the control group (p=0.004, p=0.009, p<0.001,
      p=0.002, and p=0.001, respectively). Conclusion: In addition to our knowledge
      about the effects of ICA stenosis on the retino-choroidal circulation, we found
      that OCT measurements may be beneficial in the early detection of ocular damage
      due to ICA stenosis.

PMID- 29326850
TI  - The Efficacy and Safety of Intravitreal Dexamethasone Implant for the Treatment
      of Macular Edema Related to Retinal Vein Occlusion: Real-life Data and Prognostic
      Factors in a Turkish Population.
AB  - Objectives: To evaluate the efficacy and safety of dexamethasone (DEX) implants
      as mono or combination therapy for macular edema in retinal vein occlusion (RVO)
      with real-life conditions, and to detect factors that influence final visual
      acuity. Materials and Methods: Twenty-five eyes with macular edema secondary to
      RVO underwent assessments for central macular thickness (CMT), best-corrected
      visual acuity (BCVA), adverse events, and also morphologic changes in optical
      coherence tomography at an interval of 4-8 weeks after at least one DEX implant.
      Results: Seventeen eyes with branch RVO and 8 eyes with central RVO were eligible
      for the study. The mean follow-up duration was 17 months (range, 12-26 months).
      Both mean BCVA (p=0.009) and CMT (p=0.006) improved significantly, and visual
      gains of >=3 lines were achieved in 32% and >=2 lines in 52% at the end of the
      follow-up period. The most powerful individual predictor of final visual acuity
      was baseline BCVA (r2=0.611, p<0.001, stepwise multiple regression), but the most
      efficient model was the combination of the ellipsoid zone (EZ) integrity and
      baseline BCVA (r2=0.766, p<0.001, stepwise multiple regression). Complication
      rates were very low after repeated DEX implants. Conclusion: DEX implant seems to
      be an effective and safe treatment for macular edema in RVO despite negative real
      life factors, and visual outcomes are associated with baseline visual acuity and
      EZ integrity.

PMID- 29326852
TI  - Unusual Course of Crystalline Keratopathy in a Patient with Graft-Versus-Host
      Disease.
AB  - We present a case of infectious crystalline keratopathy in a patient with Graft
      versus-Host disease (GVHD) who developed satellite fungal keratitis. A 51-year
      old man was referred for bilateral total persistent corneal epithelial defects
      with severe dry eye. Although persistent epithelial defect healed with medical
      therapy, he developed stromal keratitis with satellite lesions confirmed to be
      secondary to Candida albicans. After three months of antifungal treatment and
      debridement, improvement of the infiltrates was obtained. Crystalline keratopathy
      is an important clinical entity which may develop due to several causes. The
      microbial causes include not only bacteria but fungi as well. Careful
      investigation must be performed, especially for immune-compromised patients, in
      order to provide appropriate and timely treatment.

PMID- 29326851
TI  - Recent Advancements in Gene Therapy for Hereditary Retinal Dystrophies.
AB  - Hereditary retinal dystrophies (HRDs) are degenerative diseases of the retina
      which have marked clinical and genetic heterogeneity. Common presentations among
      these disorders include night or colour blindness, tunnel vision, and subsequent
      progression to complete blindness. The known causative disease genes have a
      variety of developmental and functional roles, with mutations in more than 120
      genes shown to be responsible for the phenotypes. In addition, mutations within
      the same gene have been shown to cause different disease phenotypes, even amongst
      affected individuals within the same family, highlighting further levels of
      complexity. The known disease genes encode proteins involved in retinal cellular
      structures, phototransduction, the visual cycle, and photoreceptor structure or
      gene regulation. Significant advancements have been made in understanding the
      genetic pathogenesis of ocular diseases, and gene replacement and gene silencing
      have been proposed as potentially efficacious therapies. Because of its favorable
      anatomical and immunological characteristics, the eye has been at the forefront
      of translational gene therapy. Recent improvements have been made in the safety
      and specificity of vector-based ocular gene transfer methods. Dozens of promising
      proofs of concept have been obtained in animal models of HRDs and some of them
      have been relayed to the clinic. The results from the first clinical trials for a
      congenital form of blindness have generated great interest and have demonstrated
      the safety and efficacy of intraocular administrations of viral vectors in
      humans. This review summarizes the clinical development of retinal gene therapy.

PMID- 29326853
TI  - Purtscher-Like Retinopathy Associated with Atypical Hemolytic Uremic Syndrome.
AB  - A 25-year-old woman presented with acute bilateral blurred vision and history of
      headache, dizziness, and syncope for three days. Her visual acuity was 20/60 in
      both eyes. Fundoscopy revealed multiple bilateral peripapillary yellow-white
      patches like cotton wool spots, intraretinal hemorrhages and macular edema. The
      patient was diagnosed with Purtscher-like retinopathy based on the retinal
      findings and lack of trauma history. She was urgently admitted to the nephrology
      clinic due to thrombotic microangiopathy findings (hemoglobinemia,
      thrombocytopenia, and acute renal failure). After excluding thrombotic
      microangiopathy, the patient was diagnosed with atypical hemolytic uremic
      syndrome (aHUS) with the clinical and laboratory findings. Eculizumab treatment
      was added to hemodialysis and plasmapheresis therapy. Three months after starting
      treatment, retinal lesions regressed and visual acuity increased to 20/20 in both
      eyes. To the best of our knowledge, this is the first reported case of Purtscher
      like retinopathy associated with aHUS.

PMID- 29326854
TI  - Macular Buckling Surgery for Retinal Detachment Associated with Macular Hole in
      High Myopia Eye.
AB  - A 68-year-old woman presented to our clinic with a 1-month history of central
      scotoma and visual loss in her right eye. The best corrected visual acuity (BCVA)
      was hand motion in her right eye. Fundus examination showed myopic chorioretinal
      degeneration in association with posterior staphyloma and the retina was slightly
      elevated throughout the macula. Optical coherence tomography (OCT) revealed
      retinal detachment involving the posterior pole with a macular hole and
      staphyloma. The patient underwent pars plana vitrectomy, internal limiting
      membrane peeling, macular buckling, and perfluoropropane gas tamponade. At 3
      month follow-up, her BCVA was improved to counting fingers at 1 meter and
      flattened retina with closed macular hole was observed by OCT. Myopic macular
      hole with retinal detachment associated with posterior staphyloma represent a
      challenge regarding their management and several surgical techniques have been
      described. Although satisfactory anatomical improvement is achieved in these eyes
      after surgery, the visual acuity outcomes may be poorer than expected due to the
      chorioretinal atrophy at the posterior pole.

PMID- 29326855
TI  - All Types of Age-related Macular Degeneration in One Patient.
AB  - Herein, we describe a neovascular age-related macular degeneration patient with
      retinal angiomatous proliferation (RAP) and polypoidal choroidal vasculopathy
      (PCV) coexisting in the same eye at the time of diagnosis. A 55-year-old woman
      presented with a history of decreased vision in her left eye. Fundoscopy,
      fluorescein and indocyanine green angiography, and optical coherence tomography
      imaging revealed RAP and PCV lesions in her left eye at first diagnosis. The
      patient received intravitreal ranibizumab therapy but developed tachyphylaxis
      after the first dose despite having three monthly doses. Switching to
      intravitreal aflibercept injection in our case resulted in anatomic and
      functional improvement.

PMID- 29326856
TI  - Using Small Case-Based Learning Groups as a Setting for Teaching Medical Students
      How to Provide and Receive Peer Feedback.
AB  - As future physicians, nearly all medical students will be required to provide
      face-to-face feedback. Moreover, receiving high quality feedback from multiple
      perspectives is particularly valuable during the pre-clerkship training period.
      To address these needs, we developed a straightforward, easy to implement
      exercise that affords students the opportunity to practice giving and receiving
      feedback with peers. We describe how this exercise has been tailored to fit
      within the case-based learning small groups of our first-year curriculum and how
      to enhance the activity by weaving the basic principles of quality feedback into
      preparation sessions. This exercise has been valued greatly by students.

PMID- 29326858
TI  - Improving Management of Paediatric Buckle Fracture in Orthopaedic Outpatients: A
      Completed Audit Loop.
AB  - Introduction Paediatric patient bone fractures are the source of a large number
      of orthopaedic outpatient visits, especially for fracture clinics. The National
      Institute for Health and Care Excellence (NICE) guideline NG38 provides guidance
      on assessing and managing non-complex fractures, such as buckle (i.e., torus)
      fractures in paediatric patients. Objective We retrospectively audited outpatient
      records of children younger than 12 years presenting with distal radius buckle
      fractures for May and June 2017. We compared our practice against the NICE
      guideline standards. We made certain changes in our practice and then repeated
      the exercise prospectively for two months from July 15 to September 15, 2017.
      Material and Methods We identified 31 patients who fit our inclusion criteria.
      After instituting changes based on the NICE guidelines, the number of children
      included in the prospective data collection was 33 patients. Results For the 31
      children treated according to our older protocol, we had 59 outpatient visits,
      with an average of 1.90 visits for every child. After the NICE-driven changes
      were made to our management, 33 patients were treated in 39 visits with an
      average of 1.2 visits per child. Conclusion Introducing NICE guidelines allowed
      for considerable improvement in the management and treatment of paediatric
      patient bone fractures. It is important to fully implement the NICE guidelines
      not only in fracture clinics but also in other departments, such as accident and
      emergency departments.

PMID- 29326857
TI  - Role of Color Doppler Flowmetry in Prediction of Intrauterine Growth Retardation
      in High-Risk Pregnancy.
AB  - OBJECTIVE: To evaluate the usefulness of Color Doppler flowmetry in the
      prediction of intrauterine growth restriction (IUGR) in high-risk pregnancies.
      MATERIALS AND METHOD: A total of 62 high-risk pregnant women underwent Color
      Doppler flowmetric umbilical artery pulsatility index (PI), resistive index (RI)
      and systolic/diastolic (S/D) ratio, middle cerebral artery PI, RI and S/D ratio,
      Ductus venosus S-wave/isovolumetric A-wave index (SIA) and vertebral artery RI at
      23-27 weeks, 28-32 weeks and 32-36 weeks of their pregnancy. Cerebral-umbilical
      C/U PI, RI and S/D were evaluated at the third visit. All the pregnancies were
      followed up till delivery. Ponderal index <10 was considered to be indicative of
      IUGR. Data were analyzed using IBM Statistical Package for Social Sciences (SPSS)
      21.0. RESULTS: Thirty-nine (62.9%) deliveries were IUGR. On all the three visits,
      umbilical artery, mean PI, RI and SD values were significantly higher while MCA
      PI, RI and SD values were significantly lower in IUGR as compared to non-IUGR
      cases. Third visit C/U PI, RI and SD ratio values were also significantly lower
      in IUGR as compared to non-IUGR cases. Ductus venosus SIA values did not show a
      significant difference between IUGR and non-IUGR groups. The vertebral artery
      resistive index was significantly higher in non-IUGR as compared to IUGR on all
      the visits. Umbilical artery PI was the most sensitive and specific for the
      prediction of IUGR at all the three visits, with the maximum sensitivity and
      specificity at the third visit (82.1% and 87%). Third visit C/U PI was most
      sensitive (82.1%) and specific (96.7%) for the prediction of IUGR. CONCLUSION:
      This showed that Doppler flowmetry is a useful method for the prediction of IUGR
      in high-risk pregnancies.

PMID- 29326859
TI  - Severe Hyponatremia Presenting with Minimal Symptoms.
AB  - Hyponatremia is a common electrolyte abnormality, however, encountering a patient
      with serum sodium level below 100 mEq/L and minimal symptoms is unusual. We
      present the case of an 86-year-old woman who was found to have serum sodium
      levels of 99 mEq/L. Her only complaint was difficulty in walking. On admission,
      and throughout her hospital stay, she did not have altered mental status, focal
      neurological deficits, or adverse outcomes. Her history, blood work, and urine
      studies pointed towards a diagnosis of thiazide-associated hyponatremia. Thiazide
      associated hyponatremia can occur at any time during the course of thiazide
      administration. The first step that should be taken to manage this condition is
      discontinuing the medication. The lesson learned from this case is that the
      degree of hyponatremia does not always correlate with the severity of symptoms.

PMID- 29326860
TI  - Retroperitoneal Mass Masquerading as Failure to Thrive in a 91-year-old Woman.
AB  - Failure to thrive (FTT) is a state of overall decline. Patients often present
      with weight loss, poor appetite, malnutrition, and decreased physical
      functioning. The etiology is multifactorial including chronic diseases,
      functional impairments, and acute illnesses. Evaluation for reversible causes is
      paramount, and treatment is aimed at maintaining or improving functional status.
      We present a case of a 91-year-old woman with a retroperitoneal mass that was
      found on workup for failure to thrive.

PMID- 29326861
TI  - Brentuximab vedotin related bilateral Purtscher-like retinopathy unresponsive to
      pulse steroid therapy and intravitreal aflibercept injection.
AB  - We describe a 36-year-old woman with a relapsing Hodgkin's lymphoma who developed
      a severe bilateral sudden visual loss almost three weeks after the initiation of
      brentuximab therapy. Ancillary fundus tests yielded bilateral severe retinal
      arteriolar occlusion 360 degrees  and serous macular retinal detachment. No
      visual improvement could be achieved despite the pulse corticosteroid therapy and
      a single bilateral intravitreal aflibercept administration cessation of the
      brentuximab therapy. Unfortunately, she succumbed to respiratory failure almost
      six weeks after the diagnosis of Purtscher-like retinopathy.

PMID- 29326862
TI  - Perfluoro-n-octane mimicking an intraocular foreign body.
AB  - Retained intraocular foreign body (IOFB) is a major cause of visual loss
      following open globe injuries. Detecting the presence and accurate localization
      of IOFB in the setting of an open globe injury remains a challenge. There can be
      various mimics of intraocular IOFB on imaging including air, ocular
      calcifications, etc. Here, we describe a case of open globe injury wherein a
      retained perfluoro-n-octane bubble mimicked a retained intraocular foreign body.

PMID- 29326863
TI  - CMV endotheliitis: a cause for recurrent failed corneal transplant.
AB  - Objective: To highlight the clinical presentation of CMV endotheliitis and the
      challenge in diagnosing this condition in recurrent failed penetrating
      keratoplasty (PK). Methods: Case series Results: There are 3 cases of recurrent
      failure in PK secondary to CMV endotheliitis presented. Case 1 and 2 were
      pseudophakic patients, while in case 3, the patient had a previous history of
      recurrent anterior uveitis. Case 1 and 3 had four and one previous failed PK
      respectively, while case 2 had endothelial keratoplasty twice before the
      diagnosis of CMV endotheliitis was made, following positive culture of aqueous
      humour. The visual acuity ranged from 1/60 to hand movement. All patients had
      pigmented KP, and two of them had typical coin-shaped KP. Oral valganciclovir was
      instituted for all patients consisting of 900 mg bidaily for two weeks, followed
      by 900 mg once daily for six months. Additionally, topical ganciclovir eyedrop
      0.5% was given every four hours with topical dexaminim four times a day. Repeated
      anterior chamber (AC) tap after six months of treatment was negative for CMV in
      case 3 while cases 1 and 2 are still on treatment. CMV endotheliitis is an
      increasingly important cause of failed corneal transplant. We recommend anterior
      chamber tap in suspicious cases of repeatedly failed corneal transplant,
      regardless of the presence of coin-shaped KP or not. Minimum treatment with oral
      valganciclovir is important to eradicate the problem, before proceeding with
      another corneal transplant. Conclusion: It is important to make an accurate early
      diagnosis by good clinical judgement in preventing loss of corneal endothelial
      cells. High index of suspicion for CMV endotheliitis as a cause of graft failure
      must be made especially when the patient presents with coin-shaped KP. Therefore
      unnecessary treatment resulting from misdiagnosis in these patients can be
      prevented. Early recognition and treatment of this condition is important to
      prevent permanent endothelial cell loss and corneal decompensation.

PMID- 29326864
TI  - Laparoscopic Finding of Ectopic Adrenocortical Tissue in a 2-Year-Old Boy with
      Vanishing Testis.
AB  - Ectopic adrenocortical tissue (EAT) along the spermatic cord is an unusual
      condition in children. The author reports on a 2-year-old boy with impalpable
      testis. On laparoscopy, EAT was detected along the hypotrophic spermatic vessels
      and excised. These remnants should be removed to prevent hormone production or
      malignant transformation.

PMID- 29326865
TI  - Rectal Atresia and Congenital Hypothyroidism: An Association or Coincidence?
AB  - Rectal atresia is a rare anorectal malformation, and its association with other
      anomalies is even more rare. This study presents a unique case of co-twin in
      which the surviving newborn male underwent surgery due to rectal atresia. Newborn
      screening tests identified congenital hypothyroidism. The surgical treatment
      consisted of three stages and thyroid hormones were replaced.

PMID- 29326867
TI  - Cavitary lung lesion suspicious for malignancy reveals Mycobacterium xenopi.
AB  - We report the case of a 68-year-old gentleman who presented with musculoskeletal
      chest pain which appeared suddenly when he bent over with his dog. The chest pain
      was localized to the left lower chest and increased with movement and deep
      breathing. The patient did not complain weight loss, night sweat, fever or chill.
      He complained of mild cough, with expectoration of whitish mucus. Imaging
      revealed cavitary chest lesion in the right upper lobe, which was initially
      suspected to be lung cancer. The patient had a 50-year-old history of smoking 2
      packs per day. PET CT imaging did not reveal any specific activity. Needle biopsy
      and bronchoalveolar lavage, however, did not reveal any malignant cells. Rather,
      necrotic tissues were observed. A wedge resection of the lung mass was performed.
      No common organisms or fungi could be grown. However, acid fast bacilli were
      observed in clumps. The morphology hinted towards non-tuberculous mycobacterial
      organism(s). Molecular studies revealed infection with Mycobacterium xenopi. The
      patient was started on an anti-tuberculous regimen of INH, rifampicin, ethambutol
      and PZA, with pyridoxine. The patient is a Vietnam veteran and complained of
      exposure to dust from a bird's nest and asbestos exposure in childhood, but no
      specific exposure to tuberculosis. The patient had an uneventful recovery post
      surgery. He complained of some nausea after initiation of the antituberculous
      medications, but his pain subsided with time. The patient had diabetes, though
      specific reasons of compromise of immune status could not be pinpointed as
      causative of his nontuberculous mycobacterial lung infection.

PMID- 29326868
TI  - Essential thrombocytemia following immune thrombocytopenia with JAK2V617F
      mutation.
AB  - JAK2V617F mutation is found in about 60% of cases of essential thrombocytemia
      (ET) and represents a driving mutation. Immune thrombocytopenia (ITP) is an
      autoimmune disease characterized by a low platelet (PLT) count. So far, only 2
      reports described ET following ITP. For the first time we analyzed in a patient
      the JAK2V617F allele burden at ITP onset occurred 13 years before the ET
      diagnosis and found the presence of a small clone JAK2V617F positive clone (3%)
      raised to 27% in the following years. The association of ET and ITP could suggest
      similar pathogenetic mechanisms that should be further investigated.

PMID- 29326866
TI  - A Review of Developmental Considerations in Human Laboratory Alcohol Research.
AB  - PURPOSE OF REVIEW: Human laboratory studies involving alcohol administration have
      generated critical knowledge about individual differences in risk for alcohol use
      disorder (AUD), but have primarily involved adult populations and cross-sectional
      research designs. Ethical constraints have largely precluded human laboratory
      alcohol research in adolescence, and prospective studies have been rare. This
      paper provides an overview of developmental considerations in human laboratory
      alcohol research, with a focus on studies conducted with youth. RECENT FINDINGS:
      Recent human laboratory studies from Europe and Canada have examined aspects of
      alcohol response during late adolescence, while recent survey studies from the
      United States have highlighted methods for circumventing alcohol administration
      in studies of adolescents. SUMMARY: Across several decades of research,
      exceedingly few laboratory studies have examined developmental differences in
      alcohol responses or utilized prospective designs. Efforts to prioritize
      prospective research would further clarify the role of alcohol sensitivity traits
      as predictors or markers of AUD onset and progression.

PMID- 29326870
TI  - Lyme carditis with isolated left bundle branch block and myocarditis successfully
      treated with oral doxycycline.
AB  - Lyme disease may present with a variety of cardiac manifestations ranging from
      first degree to third degree heart block. Cardiac involvement with Lyme disease
      may be asymptomatic, or symptomatic. Atrioventrical conduction abnormalities are
      the most common manifestation of Lyme carditis. Less common, are alternating
      right bundle branch block (RBBB) and left bundle branch block (LBBB). We present
      an interesting case of a young male whose main manifestation of Lyme carditis was
      isolated LBBB. He also had mild Lyme myocarditis. The patient was successfully
      treated with oral doxycycline, and his isolated LBBB and myocarditis rapidly
      resolved.

PMID- 29326869
TI  - Prenatal methadone exposure is associated with altered neonatal brain
      development.
AB  - Methadone is used for medication-assisted treatment of heroin addiction during
      pregnancy. The neurodevelopmental outcome of children with prenatal methadone
      exposure can be sub-optimal. We tested the hypothesis that brain development is
      altered among newborn infants whose mothers were prescribed methadone. 20
      methadone-exposed neonates born after 37 weeks' postmenstrual age (PMA) and 20
      non-exposed controls underwent diffusion MRI at mean PMA of 39+ 2 and 41+ 1
      weeks, respectively. An age-optimized Tract-based Spatial Statistics (TBSS)
      pipeline was used to perform voxel-wise statistical comparison of fractional
      anisotropy (FA) data between exposed and non-exposed neonates. Methadone-exposed
      neonates had decreased FA within the centrum semiovale, inferior longitudinal
      fasciculi (ILF) and the internal and external capsules after adjustment for GA at
      MRI (p < 0.05, TFCE corrected). Median FA across the white matter skeleton was
      12% lower among methadone-exposed infants. Mean head circumference (HC) z-scores
      were lower in the methadone-exposed group (- 0.52 (0.99) vs 1.15 (0.84), p <
      0.001); after adjustment for HC z-scores, differences in FA remained in the
      anterior and posterior limbs of the internal capsule and the ILF. Polydrug use
      among cases was common. Prenatal methadone exposure is associated with
      microstructural alteration in major white matter tracts, which is present at
      birth and is independent of head growth. Although the findings cannot be
      attributed to methadone per se, the data indicate that further research to
      determine optimal management of opioid use disorder during pregnancy is required.
      Future studies should evaluate childhood outcomes including infant brain
      development and long-term neurocognitive function.

PMID- 29326872
TI  - Phenotypic spectrum of FARS2-deficiency.

PMID- 29326871
TI  - Quantification of the enzyme activities of iduronate-2-sulfatase, N
      acetylgalactosamine-6-sulfatase and N-acetylgalactosamine-4-sulfatase using
      liquid chromatography-tandem mass spectrometry.
AB  - Mucopolysaccharidosis (MPS) is a genetic disorder characterized by the
      accumulation of glycosaminoglycans in the body. Of the multiple MPS disease
      subtypes, several are caused by defects in sulfatases. Specifically, a defect in
      iduronate-2-sulfatase (ID2S) leads to MPS II, whereas N-acetylgalactosamine-6
      sulfatase (GALN) and N-acetylgalactosamine-4-sulfatase (ARSB) defects relate to
      MPS IVA and MPS VI, respectively. A previous study reported a combined assay for
      these three disorders in a 96-well plate using a liquid chromatography-tandem
      mass spectrometry (LC-MS/MS)-based technique (Kumar et al., Clin Chem 2015
      61(11):1363-1371). In our study, we applied this methodology to a Japanese
      population to examine the assay precision and the separation of populations
      between disease-affected individuals and controls for these three disorders.
      Within our assay conditions, the coefficient of variation (CV, %) values for an
      interday assay of ID2S, GALN, and ARSB were 9%, 18%, and 9%, respectively (n =
      7). The average enzyme activities of ID2S, GALN, and ARSB in random neonates were
      19.6 +/- 5.8, 1.7 +/- 0.7, and 13.4 +/- 5.2 MUmol/h/L (mean +/- SD, n = 240),
      respectively. In contrast, the average enzyme activities of ID2S, GALN, and ARSB
      in disease-affected individuals were 0.5 +/- 0.2 (n = 6), 0.3 +/- 0.1 (n = 3),
      and 0.3 (n = 1) MUmol/h/L, respectively. The representative analytical range
      values corresponding to ID2S, GALN, and ARSB were 39, 17, and 168, respectively.
      These results raise the possibility that the population of disease-affected
      individuals could be separated from that of healthy individuals using the LC
      MS/MS-based technique.

PMID- 29326873
TI  - Motor involvement in Fabry disease.

PMID- 29326874
TI  - Only some patients with bulbar and spinal muscular atrophy may develop cardiac
      disease.
AB  - Objectives: According to recent publications, some patients with spinal and
      bulbar muscular atrophy (BSMA) develop cardiac disease, manifesting as ST-segment
      abnormalities, Brugada-syndrome, dilative cardiomyopathy, or sudden cardiac
      death. Here we present neurological and cardiac data of a BSMA patient who was
      followed up for 10 y. Case report: In a male patient aged 47 y, BSMA was
      diagnosed at age 37 y upon the typical clinical presentation (postural tremor
      since age 12 y, dysarthria since age 15 y, muscle cramps since age 29 y, general
      myalgias since age 32 y, general fasciculations since age 34 y, myoclonic jerks,
      easy fatigability, dyspnea upon exercise since age 36 y) and a CAG-repeat
      expansion of 47 +/- 1 repeats in the androgen-receptor gene detected at age 37 y.
      During the next 10 y he additionally developed mild but slowly progressive
      diffuse weakness on the upper limbs and mild proximal weakness on the lower
      limbs. Cardiologic exam, ECG, and echocardiography were normal at ages 37 y, 41
      y, 44 y, and 47 y. Conclusions: Cardiac involvement may only develop in some BSMA
      patients within 10 y, whereas neurologic abnormalities slowly progress within 10
      y of observation. Cardiac disease may develop at a later stage with progression
      of age and disease.

PMID- 29326875
TI  - Homocystinuria due to cystathionine beta-synthase (CBS) deficiency in Russia:
      Molecular and clinical characterization.
AB  - We present the results of the 45-year clinical observation of 27 Russian
      homocystinuria patients. We made a mutation analysis of the CBS gene for thirteen
      patients from eleven unrelated genealogies. All patients except for the two were
      compound heterozygotes for the mutations detected. The most frequent mutation in
      the cohort investigated was splice mutation IVS11-2a->c. We detected one new
      nonsense mutation, one new missense-mutation and three novel small deletions. We
      also report the clinical case of the B6-responsive patient genotyped as
      Ile278Thr/Cys109Arg.

PMID- 29326876
TI  - Mildly elevated succinylacetone and normal liver function in compound
      heterozygotes with pathogenic and pseudodeficient FAH alleles.
AB  - Background: A high level of succinylacetone (SA) in blood is a sensitive,
      specific marker for the screening and diagnosis of hepatorenal tyrosinemia (HT1,
      MIM 276700). HT1 is caused by mutations in the FAH gene, resulting in deficiency
      of fumarylacetoacetate hydrolase. HT1 newborns are usually clinically
      asymptomatic, but have coagulation abnormalities revealing liver dysfunction.
      Treatment with nitisinone (NTBC) plus dietary restriction of tyrosine and
      phenylalanine prevents the complications of HT1. Observations: Two newborns
      screened positive for SA but had normal coagulation testing. Plasma and urine SA
      levels were 3-5 fold above the reference range but were markedly lower than in
      typical HT1. Neither individual received nitisinone or dietary therapy. They
      remain clinically normal, currently aged 9 and 15 years. Each was a compound
      heterozygote, having a splicing variant in trans with a prevalent
      "pseudodeficient" FAH allele, c.1021C > T (p.Arg341Trp), which confers partial
      FAH activity. All newborns identified with mild hypersuccinylacetonemia in Quebec
      have had genetic deficiencies of tyrosine degradation: either deficiency of the
      enzyme preceding FAH, maleylacetoacetate isomerase, or partial deficiency of FAH
      itself. Conclusion: Compound heterozygotes for c.1021C > T (p.Arg341Trp) and a
      severely deficient FAH allele have mild hypersuccinylacetonemia and to date they
      have remained asymptomatic without treatment. It is important to determine the
      long term outcome of such individuals.

PMID- 29326877
TI  - Natural history of Morquio A patient with tracheal obstruction from birth to
      death.
AB  - Morquio A syndrome (mucopolysaccharidosis IVA, MPS IVA) is a lysosomal storage
      disease caused by a deficiency of N-acetylgalactosamine-6-sulfate sulfatase,
      resulting in systemic accumulation of the partially degraded glycosaminoglycans
      (GAGs), keratan sulfate and chondroitin-6-sulfate. The accumulation of these GAGs
      leads to distinguishing features as skeletal dysplasia with disproportionate
      dwarfism, short neck, kyphoscoliosis, pectus carinatum, tracheal obstruction,
      coxa valga, genu valgum, and joint laxity. In the absence of autopsied cases and
      systemic analysis of multiple tissues, the pathological mechanism of the
      characteristic skeletal dysplasia associated with the disease largely remains a
      question. Here we report an autopsied case of a 23-year-old male with MPS IVA,
      who developed characteristic skeletal abnormalities by 4 months of age and died
      of severe tracheal obstruction and hypoventilation originating from respiratory
      muscle weakness from neurological cord deficit due to cord myelopathy at the age
      of 23. We analyzed postmortem tissues pathohistologically, including the thyroid,
      lung, lung bronchus, trachea, heart, aorta, liver, spleen, kidney, testes,
      humerus, knee cartilage, and knee ligament. Examination of the tissues
      demonstrated systemic storage materials in multiple tissues, as well as severely
      ballooned and vacuolated chondrocytes in the trachea, humerus, knee cartilage,
      and lung bronchus. This autopsied case with MPS IVA addresses the importance of
      tracheal obstruction for morbidity and mortality of the disease, and the
      pathological findings contribute to a further understanding of the pathogenesis
      of MPS IVA and the development of novel therapies.

PMID- 29326878
TI  - Ten-year-long enzyme replacement therapy shows a poor effect in alleviating giant
      leg ulcers in a male with Fabry disease.
AB  - Fabry disease is an X-linked lysosomal storage disorder caused by a deficiency of
      alpha-galactosidase A (alpha-gal A), leading to the progressive accumulation of
      glycosphingolipids. Classical hemizygous males usually present symptoms,
      including pain and paresthesia in the extremities, angiokeratoma, hypo- or
      anhidrosis, abdominal pain, cornea verticillata, early stroke, tinnitus, and/or
      hearing loss, during early childhood or adolescence. Moreover, proteinuria, renal
      impairment, and cardiac hypertrophy can appear with age. Enzyme replacement is
      the most common therapy for Fabry disease at present which has been approved in
      Japan since 2004. We report a case involving a 27-year-old male with extreme
      terminal pain, anhidrosis, abdominal pain, tinnitus, hearing impairment, cornea
      verticillata, and recurrent huge ulcers in the lower extremities. At the age of
      16 years, he was diagnosed with Fabry disease with a positive family history and
      very low alpha-gal A activity. He then received enzyme replacement therapy (ERT)
      with recombinant human agalsidase beta at 1 mg/kg every 2 weeks for 10 years.
      Throughout the course of ERT, his leg ulcers recurred, and massive excretion of
      urinary globotriaosylceramide and plasma globotriaosylsphingosine was observed.
      Electron microscopy of the venous tissue in the regions of the ulcer showed
      massive typical zebra bodies in the vascular wall smooth muscle cells.

PMID- 29326879
TI  - Characteristics of 26 patients with type 3 Gaucher disease: A descriptive
      analysis from the Gaucher Outcome Survey.
AB  - The Gaucher Outcome Survey (GOS) is an international disease-specific registry
      established in 2010 for patients with a confirmed diagnosis of Gaucher disease
      (GD), regardless of GD type or treatment status. Historically, there has been a
      limited understanding of type 3 GD (GD3) and its natural history in patients
      irrespective of their treatment status. Here, we describe the disease
      characteristics of patients with GD3 enrolled in GOS. As of October 2015, 1002
      patients had been enrolled, 26 of whom were reported as GD3. The majority of
      patients with GD3 were from the US (13; 50.0%), seven (26.9%) were from the UK,
      three (11.5%) from Israel, and three (11.5%) from Brazil. No patients were of
      Ashkenazi Jewish origin. Median age of symptom onset was 1.4 (interquartile
      range: 0.5-2.0) years. The most common GBA1 mutation genotype was L444P/L444P,
      occurring in 16 (69.6%) of 23 patients who had genotyping information available.
      Nine patients reported a family history of GD (any type). Of 21 patients with
      treatment status information, 20 (95.2%) had received GD-specific treatment at
      any time, primarily imiglucerase (14 patients) and/or velaglucerase alfa (13
      patients). Hemoglobin concentrations and platelet counts at GOS entry were within
      normal ranges for most patients, and there were no reports of severe hepatomegaly
      or of splenomegaly in non-splenectomized patients, most likely indicative of the
      effects of treatment received prior to GOS entry. This analysis provides
      information on the characteristics of patients with GD3 that could be used as the
      baseline for longitudinal follow-up of these patients.

PMID- 29326880
TI  - Blood phenylalanine instability strongly correlates with anxiety in
      phenylketonuria.
AB  - We assessed the relationship between anxiety and long-term metabolic control in
      adolescents with phenylketonuria (PKU). We used a standardized psychological test
      to measure anxiety level and analyzed lifelong blood phenylalanine stability in a
      selected group of 25 PKU teenagers with treatment adherence problems. We
      demonstrated significant correlations of anxiety with variability of blood
      phenylalanine concentrations and with severity of hyperphenylalaninemia. Avoiding
      blood phenylalanine fluctuations in childhood can probably reduce anxiety in PKU
      adolescents.

PMID- 29326881
TI  - Interaction of anthraquinones of Cassia occidentalis seeds with DNA and
      Glutathione.
AB  - Consumption of Cassia occidentalis (CO) seeds has been associated with the
      hepatomyoencephalopathy (HME) in children. Recently, we have characterized the
      toxic anthraquinones (AQs) such as Emodin, Rhein, Aloe-emodin, Chrysophanol and
      Physcion in CO seeds and detected these moieties in the bio fluids of CO
      poisoning cases. As AQs were detected in the serum of HME patients, their
      interaction with key biomolecules including protein, DNA and glutathione (GSH) is
      imperative. In this regard, we have previously reported the interaction of these
      AQs with serum albumin protein and their subsequent biological effects. However,
      the interaction of these AQs with DNA and GSH remained unexplored. In the present
      work, we have studied the binding of these AQs of CO seeds with DNA and GSH by
      fluorescence spectroscopy, UV-vis spectral analysis, molecular docking, and
      biochemical studies. Results indicated a higher binding affinity for Emodin (Ka =
      3.854 * 104 L mol-1 S-1), Aloe-emodin (Ka = 0.961 * 104 L mol-1 S-1) and Rhein
      (Ka = 0.034 * 104 L mol-1 S-1) towards calf thymus DNA may be associated with
      their higher cytotoxicity. Alternatively, Physcion and Chrysophanol which showed
      less cytotoxicity in our earlier studies exhibited very low DNA binding. The
      binding pattern of all these AQs is consistent with the in-silico data.
      Absorption spectroscopy studies indicated the possible formation of GSH conjugate
      with Aloe-emodin and Physcion. Further biochemical measurement of GSH and GSSG
      (Glutathione disulfide) following incubation with AQs indicated that Aloe-emodin
      (28%) and Rhein (30%) oxidizes GSH to GSSG more as compared to other AQs. Taken
      together, these results suggest that the higher cytotoxicity of Rhein, Emodin and
      Aloe-emodin may be attributed to their potent DNA and GSH binding affinity.

PMID- 29326882
TI  - The Role of Class IA Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic
      Subunits in Glioblastoma.
AB  - Phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) plays a critical role in
      the pathogenesis of cancer including glioblastoma, the most common and aggressive
      form of brain cancer. Targeting the PI3K pathway to treat glioblastoma has been
      tested in the clinic with modest effect. In light of the recent finding that PI3K
      catalytic subunits (PIK3CA/p110alpha, PIK3CB/p110beta, PIK3CD/p110delta, and
      PIK3CG/p110gamma) are not functionally redundant, it is imperative to determine
      whether these subunits play divergent roles in glioblastoma and whether
      selectively targeting PI3K catalytic subunits represents a novel and effective
      strategy to tackle PI3K signaling. This article summarizes recent advances in
      understanding the role of PI3K catalytic subunits in glioblastoma and discusses
      the possibility of selective blockade of one PI3K catalytic subunit as a
      treatment option for glioblastoma.

PMID- 29326883
TI  - Metabolic Plasiticy in Cancers-Distinct Role of Glycolytic Enzymes GPI, LDHs or
      Membrane Transporters MCTs.
AB  - Research on cancer metabolism has recently re-surfaced as a major focal point in
      cancer field with a reprogrammed metabolism no longer being considered as a mere
      consequence of oncogenic transformation, but as a hallmark of cancer.
      Reprogramming metabolic pathways and nutrient sensing is an elaborate way by
      which cancer cells respond to high bioenergetic and anabolic demands during
      tumorigenesis. Thus, inhibiting specific metabolic pathways at defined steps
      should provide potent ways of arresting tumor growth. However, both animal models
      and clinical observations have revealed that this approach is seriously limited
      by an extraordinary cellular metabolic plasticity. The classical example of
      cancer metabolic reprogramming is the preference for aerobic glycolysis, or
      Warburg effect, where cancers increase their glycolytic flux and produce lactate
      regardless of the presence of the oxygen. This allows cancer cells to meet the
      metabolic requirements for high rates of proliferation. Here, we discuss the
      benefits and limitations of disrupting fermentative glycolysis for impeding tumor
      growth at three levels of the pathway: (i) an upstream block at the level of the
      glucose-6-phosphate isomerase (GPI), (ii) a downstream block at the level of
      lactate dehydrogenases (LDH, isoforms A and B), and (iii) the endpoint block
      preventing lactic acid export (MCT1/4). Using these examples of genetic
      disruption targeting glycolysis studied in our lab, we will discuss the responses
      of different cancer cell lines in terms of metabolic rewiring, growth arrest, and
      tumor escape and compare it with the broader literature.

PMID- 29326884
TI  - Primary Orbital Melanoma: Presentation, Treatment, and Long-term Outcomes for 13
      Patients.
AB  - Background: Periocular melanoma is a rare but often deadly malignancy that arises
      in the uvea (commonest origin), conjunctiva or orbit (rarest primary site).
      Melanoma accounts for 5-10% of metastatic/secondary orbital malignancies, but
      only a tiny proportion of primary orbital neoplasia. Primary orbital melanoma
      (POM) is exceedingly rare, with approximately 50 cases reported to date. Methods:
      All patients seen in the orbital unit at a tertiary referral hospital (1991-2016)
      with a biopsy-proven diagnosis of POM were identified from a diagnostic database
      and were studied. The case notes, imaging, surgical approach, and histology were
      reviewed. Results: Thirteen patients (five male; 38%) presented with isolated
      malignant melanoma of the orbit, for which no other primary site was identified
      at presentation or during an average follow-up of 44 months (median 22; range 0
      13 years). The patients presented between the ages of 40 and 84 years (mean 55.5;
      median 48 years) and typically gave a short history of rapidly increasing
      proptosis and eyelid swelling. On the basis of history, a malignant lesion was
      suspected in most patients and all underwent incisional biopsy, with debulking of
      the mass in 10 (77%) patients, and skin-sparing exenteration in 3/13 (23%). Ten
      patients underwent orbital radiotherapy and the survival to date ranged from 9
      months to 14 years (mean 55 months; median 23 months); two patients received
      solely palliative care for widespread disease and one patient refused orbital
      radiotherapy. Five of the 13 (38%) patients died from the disease. Discussion:
      POM is a very rare malignancy, but clinical analysis of this cohort gives insight
      into disease presentation and prognosis. The tumor typically presents with a
      rapidly progressive, well-defined mass that is, in some cases, amenable to
      macroscopically intact excision. Unusual for malignant melanoma, some of these
      patients can show an unusually long period of quiescent disease after surgical
      debulking and radiotherapy.

PMID- 29326886
TI  - Oral Microbiota: Microbial Biomarkers of Metabolic Syndrome Independent of Host
      Genetic Factors.
AB  - The oral microbiota plays a critical role in both local and systemic
      inflammation. Metabolic syndrome (MetS) is characterized by low-grade
      inflammation, and many studies have been conducted on the gut microbiota from
      stool specimens. However, the etiological role of the oral microbiota in the
      development of MetS is unclear. In this study, we analyzed the oral and gut
      microbiome from 228 subgingival plaque and fecal samples from a Korean twin
      family cohort with and without MetS. Significant differences in microbial
      diversity and composition were observed in both anatomical niches. However, a
      host genetic effect on the oral microbiota was not observed. A co-occurrence
      network analysis showed distinct microbiota clusters that were dependent on the
      MetS status. A comprehensive analysis of the oral microbiome identified
      Granulicatella and Neisseria as bacteria enriched in subjects with MetS and
      Peptococcus as bacteria abundant in healthy controls. Validation of the
      identified oral bacteria by quantitative PCR (qPCR) showed that healthy controls
      possessed significantly lower levels of G. adiacens (p = 0.023) and a higher
      ratio of Peptococcus to Granulicatella (p < 0.05) than MetS subjects. Our results
      support that local oral microbiota can be associated with systemic disorders. The
      microbial biomarkers identified in this study would aid in determination of which
      individuals develop chronic diseases from their MetS and contribute to strategic
      disease management.

PMID- 29326889
TI  - Office/home-based exercise rehabilitation is useful for computer-based workers in
      today's world.

PMID- 29326888
TI  - Season's greetings.

PMID- 29326885
TI  - Chlamydia abortus Pmp18.1 Induces IL-1beta Secretion by TLR4 Activation through
      the MyD88, NF-kappaB, and Caspase-1 Signaling Pathways.
AB  - The polymorphic membrane protein D (Pmp18D) is a 160-kDa outer membrane protein
      that is conserved and plays an important role in Chlamydia abortus pathogenesis.
      We have identified an N-terminal fragment of Pmp18D (designated Pmp18.1) as a
      possible subunit vaccine antigen. In this study, we evaluated the vaccine
      potential of Pmp18.1 by investigating its ability to induce innate immune
      responses in dendritic cells and the signaling pathway(s) involved in rPmp18.1
      induced IL-1beta secretion. We next investigated the immunomodulatory impact of
      VCG, in comparison with the more established Th1-promoting adjuvants, CpG and FL,
      on rPmp18.1-mediated innate immune activation. Finally, the effect of siRNA
      targeting TLR4, MyD88, NF-kappaB p50, and Caspase-1 mRNA in DCs on IL-1beta
      cytokine secretion was also investigated. Bone marrow-derived dendritic cells
      (BMDCs) were stimulated with rPmp18.1 in the presence or absence of VCG or CpG or
      FL and the magnitude of cytokines produced was assessed using a multiplex
      cytokine ELISA assay. Expression of costimulatory molecules and Toll-like
      receptors (TLRs) was analyzed by flow cytometry. Quantitation of intracellular
      levels of myeloid differentiation factor 88 (MyD88), nuclear factor kappa beta
      (NF-kappaB p50/p65), and Caspase-1 was evaluated by Western immunoblotting
      analysis while NF-kappaB p65 nuclear translocation was assessed by confocal
      microscopy. The results showed DC stimulation with rPmp18.1 provoked the
      secretion of proinflammatory cytokines and upregulated expression of TLRs and co
      stimulatory molecules associated with DC maturation. These responses were
      significantly (p <= 0.001) enhanced by VCG but not CpG or FL. In addition,
      rPmp18.1 activated the expression of MyD88, NF-kappaB p50, and Caspase-1 as well
      as the nuclear expression of NF-kappaB p65 in treated DCs. Furthermore, targeting
      TLR4, MyD88, NF-kappaB p50, and Caspase-1 mRNA in BMDCs with siRNA significantly
      reduced their expression levels, resulting in decreased IL-1beta cytokine
      secretion, strongly suggesting their involvement in the rPmp18.1-induced IL-1beta
      cytokine secretion. Taken together, these results indicate that C. abortus
      Pmp18.1 induces IL-1beta secretion by TLR4 activation through the MyD88, NF
      kappaB as well as the Caspase-1 signaling pathways and may be a potential C.
      abortus vaccine candidate. The vaccine potential of Pmp18.1 will subsequently be
      evaluated in an appropriate animal model, using VCG as an immunomodulator,
      following immunization and challenge.

PMID- 29326890
TI  - How can we reduce injuries and illnesses among athletes during the PyeongChang
      2018 Olympic Winter Games?

PMID- 29326887
TI  - Streptococcus mutans Displays Altered Stress Responses While Enhancing Biofilm
      Formation by Lactobacillus casei in Mixed-Species Consortium.
AB  - Like Streptococcus mutans, lactobacilli are commonly isolated from carious sites,
      although their exact role in caries development remains unclear. This study used
      mixed-species models to analyze biofilm formation by major groups of oral
      lactobacilli, including L. casei, L. fermentum, L. rhamnosus, L. salivarius ssp.
      salivarius, and L. gasseri. The results showed that lactobacilli did not form
      good biofilms when grown alone, although differences existed between different
      species. When grown together with S. mutans, biofilm formation by L. gasseri and
      L. rhamnosus was increased by 2-log (P < 0.001), while biofilms by L. fermentum
      reduced by >1-log (P < 0.001). L. casei enhanced biofilm formation by ~2-log when
      grown with S. mutans wild-type, but no such effects were observed with S. mutans
      deficient of glucosyltransferase GtfB and adhesin P1. Both S. mutans and L. casei
      in dual-species enhanced resistance to acid killing with increases of survival
      rate by >1-log (P < 0.001), but drastically reduced the survival rates following
      exposure to hydrogen peroxide (P < 0.001), as compared to the respective mono
      species cultures. When analyzed by RNA-seq, more than 134 genes were identified
      in S. mutans in dual-species with L. casei as either up- or down-regulated when
      compared to those grown alone. The up-regulated genes include those for
      superoxide dismutase, NADH oxidase, and members of the mutanobactin biosynthesis
      cluster. Among the down-regulated genes were those for GtfB and alternative sigma
      factor SigX. These results further suggest that interactions between S. mutans
      and oral lactobacilli are species-specific and may have significant impact on
      cariogenic potential of the community.

PMID- 29326891
TI  - Role of exercise on molecular mechanisms in the regulation of antidepressant
      effects.
AB  - Regular exercise reduces depressive-like behavior activation. In this study, we
      look for exact roles of exercise on molecular and neuronal mechanisms for
      antidepressant action by studying the hippocampal neuroplasticity and
      proliferation. Increased hippocampal neurogenesis with exercise has potential
      significance for depression. Exercise promotes brain health in the molecular
      levels in the hippocampus and also affects behavior in a similar way to chronic
      antidepressant treatment. Wingless (Wnt) and frizzled signaling system plays an
      important role in cell proliferation, growth, and differentiation during
      development. Our results demonstrate complicated, differential effects of
      antidepressants on Wnt signaling system, and assume a role for selected signaling
      molecules in the neurogenic activity of antidepressant care. Our review suggests
      that exercise may preserve brain function by increasing neurogenesis through
      activating Wnt signaling pathway in the psychiatric disorders, such as
      depression.

PMID- 29326892
TI  - Role of transforming growth factor-beta in muscle damage and regeneration:
      focused on eccentric muscle contraction.
AB  - High-intensity eccentric muscle contraction induces muscle damage. Damaged
      muscles recover through different processes, including degeneration,
      inflammation, regeneration, and fibrosis; some of these processes are mediated
      through the actions of cytokines. The transforming growth factor-beta (TGF-beta)
      is one such cytokine involved in muscle recovery and repair. In this regard, TGF
      beta regulates the skeletal muscle inflammatory response, inhibits muscle
      regeneration, regulates extracellular matrix remodeling, and promotes fibrosis.
      Although some studies have suggested that inhibition of TGF-beta after muscle
      damage promotes muscle regeneration and recovery, other studies have noted that
      TGF-beta inhibition actually reduces muscle strength because it leads to
      incomplete muscle regeneration. Despite the importance of TGF-beta in the repair
      of damaged muscles, most studies have focused on examining its role in muscle
      diseases such as chronic inflammatory diseases or Duchenne's muscular dystrophy.
      Here, we have reviewed the existing literature for examining the role of TGF-beta
      in muscle damage and regeneration after eccentric muscle contraction.

PMID- 29326894
TI  - Comparison study for body image education of domestic and overseas female college
      students.
AB  - The 2016 health education index showed such tendency as well including their
      raised obesity index, and reported that they are much interested in body images
      appearing externally. Accordingly, in this study, we conducted the self-reported
      questionnaire aimed at a total of 389 subjects composed of domestic (n= 226) and
      overseas (n= 163) female college students from Asia, Europe, and Latin America so
      as to investigate their body images for face, figure and health through
      questionnaires. In this context, a survey was conducted with the method of this
      study, consequently indicating that overseas subjects are more greatly positive
      and active to body images (face, figure, and health) by health level, exercise
      preferences, extent of body activities and body weight than domestic ones. These
      results reflect a different viewpoint between those subjects and reveal that
      overseas subjects are more committed to maintaining their health through body
      activities compared to domestic ones. Moreover, it is considered that domestic
      subjects tend to place a higher value on external beauty rather than beauty in
      terms of physical health, thereby it is most important to change the beauty
      values. Therefore, in the future, health education should play a critical role in
      promoting discussions for plans and practical strategies of improving health
      between students and in participating actively in health behaviours.

PMID- 29326893
TI  - Treadmill exercise ameliorates social isolation-induced depression through
      neuronal generation in rat pups.
AB  - Social isolation is known to induce emotional and behavioral changes in animals
      and humans. The effect of treadmill exercise on depression was investigated using
      social isolated rat pups. The rat pups in the social isolation groups were housed
      individually. The rat pups in the exercise groups were forced to run on treadmill
      for 30 min once a day from postnatal day 21 to postnatal day 34. In order to
      evaluate depression state of rat pups, forced swimming test was performed. Newly
      generated cells in the hippocampal dentate gyrus were determined by 5-bromo-2'
      deoxyuridine (BrdU) immunohistochemistry. We examined the expression of 5
      hydroxytryptamine (5-HT) and tryptophan hydroxylase (TPH) in the dorsal raphe
      using immunofluorescence. The expression of brain-derived neurotrophic factor
      (BDNF) and tyrosine kinase B (TrkB) was detected by Western blot analysis. The
      present results demonstrated that social isolation increased resting time and
      decreased mobility time. Expression of 5-HT and TPH in the dorsal raphe and
      expression of BDNF and TrkB in the hippocampus were decreased by social
      isolation. The number of BrdU-positive cells in the hippocampal dentate gyrus was
      suppressed by social isolation. Treadmill exercise decreased resting time and
      increased mobility in the social isolated rat pups. Expression of 5-HT, TPH,
      BDNF, and TrkB was increased by treadmill exercise. The present results suggested
      that treadmill exercise may ameliorates social isolation-induced depression
      through increasing neuronal generation.

PMID- 29326895
TI  - Effects of walking with hand-held weights on energy expenditure and excess
      postexercise oxygen consumption.
AB  - Walking is not only important to assist in performing daily tasks, but also to
      gain cardiovascular benefits. Further research on walking is needed to examine
      the physiological responses to improve health and reduce the risks of
      cardiovascular disease. The purpose of this study was to compare the energy
      expenditure (EE) during and after walking exercise with versus without hand-held
      weights (HHW). Nineteen sedentary women (mean+/-standard deviation; age, 21+/-2.7
      years, height, 163.1+/-6.3 cm; body mass, 66.6+/- 15.1 kg; body fat %, 30.6%+/-
      7.43%; body mass index, 25.5+/- 5.7 kg/m2) volunteered walking with versus
      without 1.36 kg of HHW in two randomized sessions. The study consisted of 30 min
      of exercise followed b silent sitting for 30 min. The range of motion was set at
      elbow flexion at 90 degrees  while arms were alternated 30.48 cm forward and
      backward. 1% incline was set for the treadmill grade and speed was controlled to
      a moderate level of 40%-59% of heart rate reserve. During the 30-min exercise no
      significant differences were found between the conditions (P> 0.05). The
      physiological responses were significantly greater directly after exercise
      compared with baseline as determined from pairwise comparisons collapsed across
      conditions (P<= 0.05). Walking with HHW was not substantial enough to raise EE
      beyond normal walking and led to an increased effort level. Additionally, the
      moderate intensity of walking was not enough to sustain EE at a surpassing level
      directly after the exercise.

PMID- 29326896
TI  - Relationship between sitting volleyball performance and field fitness of sitting
      volleyball players in Korea.
AB  - The purpose of this study was to evaluate the relationship between sitting
      volleyball performance and the field fitness of sitting volleyball players. Forty
      five elite sitting volleyball players participated in 10 field fitness tests.
      Additionally, the players' head coach and coach assessed their volleyball
      performance (receive and defense, block, attack, and serve). Data were analyzed
      with SPSS software version 21 by using correlation and regression analyses, and
      the significance level was set at P< 0.05. The results showed that chest pass,
      overhand throw, one-hand throw, one-hand side throw, splint, speed endurance,
      reaction time, and graded exercise test results had a statistically significant
      influence on the players' abilities to attack, serve, and block. Grip strength, t
      test, speed, and agility showed a statistically significant relationship with the
      players' skill at defense and receive. Our results showed that chest pass,
      overhand throw, one-hand throw, one-hand side throw, speed endurance, reaction
      time, and graded exercise test results had a statistically significant influence
      on volleyball performance.

PMID- 29326897
TI  - Effect of vigorous physical activity on blood lipid and glucose.
AB  - The aim of the study is to investigate how the participation of vigorous physical
      activities in the health examination contributes to blood lipid and blood
      glucose. A total of 56,810 workers from the Ulsan University Hospital in Ulsan,
      Subjects were tested for health checkups from February to November in 2016. The
      subject is those who does not have medical history, current ailments, and
      medication histories, and selected those who conducted the study of subjects
      tested to research. And this study did not consider their drinking and smoking.
      The final selected population was 11,557 and categorized as a vigorous physical
      activity of the health survey items. In this study, the group participated by the
      vigorous physical activity activities, group 1 (n= 70) had more than 6 days of
      vigorous physical activity, group 2 (n= 2,960) is 3 to 5 days of vigorous
      physical activity, the group 3 (n= 7,389) is 1 to 2 days of vigorous physical
      activity. The group 4 (n= 1,138) were classified as those who did not perform
      vigorous physical activity. To achieve the purpose of the study, the
      questionnaire examined blood lipid and blood glucose, using questions related to
      physical activity related to health examination in the Ulsan University Hospital.
      We obtained the mean and standard deviation for each group and conducted the one
      way analysis of variance as an independent variable. Post hoc is least
      significant difference test and significant level is 0.05. Vigorous physical
      activity more than 3 days of participation had a positive affect high-density
      lipoprotein cholesterol and triglyceride. But participation in vigorous physical
      activity did not affect blood glucose.

PMID- 29326898
TI  - Effect of 10% weight loss on simulated taekwondo match performance: a randomized
      trial.
AB  - The objective of the present study was to analyze the effect of 10% body mass
      reduction on simulated taekwondo match performance. Thirty-one male taekwondo
      athletes were randomly distributed in two groups: weight loss group (n= 15) -
      athletes in this group reduced 5% body mass per week during two successive weeks,
      totaling 10% body mass reduction; control group (n= 16) - athletes in this group
      kept their body mass constant during the 2-week period. Twenty-four hours before
      and after this period, athletes performed a simulated 3-round taekwondo match (6
      min). Athletes wore body protectors to validate the scores during the match
      according to the official taekwondo rules. Match was filmed and actions were
      categorized using the Game Performance Assessment Instrument. There was a group
      and time interaction (P< 0.001) for body mass, with decrease only for the weight
      loss group (P= 0.001). A group and time interaction was also observed for the
      taekwondo match performance (P< 0.001), with performance increase being found
      only for the control group (P= 0.01). Thus, the 10% weight loss was not a good
      strategy to improve taekwondo skills' performance.

PMID- 29326899
TI  - Effectiveness of a multimodal exercise rehabilitation program on walking capacity
      and functionality after a stroke.
AB  - The aim of this study was to determine the effectiveness of a 12-week multimodal
      exercise rehabilitation program on walking speed, walking ability and activities
      of daily living (ADLs) among people who had suffered a stroke. Thirty-one stroke
      survivors who had completed a conventional rehabilitation program voluntarily
      participated in the study. Twenty-six participants completed the multimodal
      exercise rehabilitation program (2 days/wk, 1 hr/session). Physical outcome
      measures were: walking speed (10-m walking test), walking ability (6-min walking
      test and functional ambulation classification) and ADLs (Barthel Index). The
      program consisted on: aerobic exercise; task oriented exercises; balance and
      postural tonic activities; and stretching. Participants also followed a program
      of progressive ambulation at home. They were evaluated at baseline,
      postintervention and at the end of a 6-month follow-up period. After the
      intervention there were significant improvements in all outcomes measures that
      were maintained 6 months later. Comfortable and fast walking speed increased an
      average of 0.16 and 0.40 m/sec, respectively. The walking distance in the 6-min
      walking test increased an average of 59.8 m. At the end of the intervention,
      participants had achieved independent ambulation both indoors and outdoors. In
      ADLs, 40% were independent at baseline vs. 64% at the end of the intervention.
      Our study demonstrates that a multimodal exercise rehabilitation program adapted
      to stroke survivors has benefits on walking speed, walking ability and
      independence in ADLs.

PMID- 29326900
TI  - Development of strategies for changing in physical activity behaviors on older
      adults with disabilities.
AB  - The purpose of this study was to develop strategies for promoting physical
      activity for the disabled older adults who were in the transtheoretical model of
      precontemplation, contemplation, and preparation stages about participating
      physical activities for promoting healthy life-styles. In order to achieve this
      goal, we developed a preliminary strategy for promoting physical activity for the
      elderly with disabilities based on the data gathered through the ground-work
      studies and the results of the research on the changes of the exercise behavior
      directly investigated from the elderly with disabilities. Then the strategies
      were verified to completion of the final promoting strategies. The elderly with
      disabilities in the three stages of precontemplation, contemplation, and
      preparation should develop strategies to think positively about themselves and
      their surroundings as well as strengthen their appropriate healthy behaviors.
      Additionally, families, physicians, and healthy seniors who spent time with
      disabled older adults could help to promote physical activities. However, overall
      administrative support, in-stitutional system construction, and public policy
      support were needed and it suggested that multifaceted supports and a variety of
      cooperation were necessary to improve a quality of life among older adults with
      disabilities.

PMID- 29326901
TI  - Short-term effects of Theracurmin dose and exercise type on pain, walking
      ability, and muscle function in patients with knee osteoarthritis.
AB  - The purpose of this study was to investigate the short-term of Theracurmin dose
      and exercise type on pain, walking ability, and muscle function in patients with
      knee osteoarthritis. Twenty-five patients with knee osteoarthritis randomly
      selected to Theracurmin intake (T) group and Theracurmin in combined with
      exercise (T+E) group. T group (n= 13) was taken orally a capsule of 700 mg, 3
      times per day, (total 2,100 mg, 35 mg/kg-body weight). T+E group (n= 12)
      performed aerobic training of 30-min walking and weight training for increasing
      leg muscular strength. After treatment, the number of steps, muscle mass, range
      of motion of knee, and the muscle strength in flexion and extension significantly
      increased. The percent body fat, visual analogue scale, The Western Ontario and
      McMaster score, centers of pressure with closed eye, 10-m walking ability, stair
      ascending speed were significantly decreased after treatment. Although no
      difference observed between the T and T+E groups, the 4-week intake of
      Theracurmin with and without exercise appeared to be effective in reducing the
      pain and enhancing muscular and balancing function. Therefore, Theracurmin intake
      for early symptoms and additional exercise as symptoms alleviate might be an
      effective way of delaying and managing osteoarthritis, and additional studies
      investigating the effects of Theracurmin and exercise on osteoarthritis could be
      beneficial.

PMID- 29326902
TI  - Low-intensity training provokes adaptive extracellular matrix turnover of a
      muscular dystrophy model.
AB  - Recommendations of therapeutic exercise in Duchenne muscular dystrophy are still
      controversial. The hypothesis that a low-intensity training (LIT) protocol leads
      to muscle adaptations on mdx mice model was tested. Dystrophic male mice with 8
      weeks old were separated in exercised (mdxE, n= 8) and sedentary (mdxC, n= 8)
      groups. Wild-type mice were used as control (WT, n= 8) group. Exercised group
      underwent a LIT protocol (9 m/min, 30 min, 3 days/wk, 60 days) on a horizontal
      treadmill. At day 60 all animals were analyzed regarding parameters of markers of
      muscle lesion and extracellular matrix turnover of muscle tissue by collagens
      fibers on tibial anterior muscle. Histomorphometry attested that centrally
      located nuclei fibers and the coefficient of variance of minimal Feret's diameter
      was similar in mdxE and mdxC groups (P= 1.000) and both groups presented higher
      mean values than WT group (P< 0.001). Fraction area of collagen fibers of mdxE
      group was lower than mdxC group (P= 0,027) and similar to WT group (P= 0,751).
      Intramuscular area of Col3 of the mdxE group was higher than mdxC and WT groups
      (P<0.001). Intramuscular area of Col1 on the mdxE group was similar to the mdxC
      group (P= 1.000) and both groups were higher than WT group (P< 0.001). LIT
      protocol had not influenced muscle injuries resulting from the dystrophin
      deficiency membrane fragility. Although, LIT had provoked adaptations on
      extracellular matrix bringing higher elastic feature to dystrophic muscle tissue.

PMID- 29326903
TI  - Inter- and intrarater reliability of goniometry and hand held dynamometry for
      patients with subacromial impingement syndrome.
AB  - The purpose of this study was to examine the intra- and interrater reliability of
      measuring shoulder range of motion (ROM) and strength among patients diagnosed
      with subacromial impingement syndrome (SAIS). Twenty-five patients (14 female
      patients; mean age, 60.4+/- 7.84 years) diagnosed with SAIS were assessed to
      determine the intrarater reliability for glenohumeral ROM. Twenty-five patients
      (16 female patients; mean age, 60.4+/- 7.80 years) and 76 asymptomatic volunteers
      (52 female volunteers; mean age, 29.4+/- 14.1 years) were assessed for interrater
      reliability. Dependent variables were active shoulder ROM and isometric strength.
      Intrarater reliability was fair-to-excellent for the SAIS patients (intraclass
      correlation coefficient [ICC], 0.52-0.97; standard error of measurement [SEM],
      4.4 degrees -9.9 degrees  N; coefficient of variation [CV], 7.1%-44.9%). Based on
      the ICC, 11 of 12 parameters (92%) displayed an excellent reliability (ICC>
      0.75). The interrater reliability showed fair-to-excellent results (SAIS
      patients: ICC, 0.13-0.98; SEM, 2.3 degrees -8.8 degrees ; CV, 3.6%-37.0%;
      controls: ICC, 0.11-0.96; SEM, 3.0 degrees -35.4 degrees ; CV, 5.6%-26.4%). In
      accordance with the intrarater reliability, glenohumeral adduction ROM was the
      only parameter with an ICC below 0.75 for both samples. Painful shoulder ROM in
      the SAIS patients showed no influence on the quality of reliability for
      measurement. Therefore, these protocols should be considered reliable assessment
      techniques in the prevention, diagnosis, and treatment of painful shoulder
      conditions such as SAIS.

PMID- 29326904
TI  - Effects of habitual smoking on cardiopulmonary function in taekwondo athletes.
AB  - This study aimed to verify habitual smoking effects on cardiopulmonary function
      in taekwondo athletes. Subjects were university taekwondo athletes aged 20-24
      years in nonsmoker (n= 9) and smoker (n= 6) groups. Subjects underwent an
      exercise examination for their ventilation threshold, minute ventilation, oxygen
      uptake, maximum volume of minute oxygen consumption, heart rate, and oxygen pulse
      during exercise and 1, 3, and 5 min after maximum exercise. The time of reaching
      the ventilation threshold was significantly higher in nonsmokers than in smokers.
      Heart rate during recovery after maximum exercise was significantly lower in
      nonsmokers for 1 and 3 min. Nonsmokers had significantly higher time for reaching
      the ventilation threshold and heart rate recovery at 1 and 3 min after exercise.
      The higher timing of accumulation fatigue in ventilation amount and faster
      recovery after exercise are useful in continuous exercise and improving athletic
      performance. Thus, athletes should stop smoking as soon as possible to improve
      their aerobic physical fitness and athletic performance.

PMID- 29326905
TI  - Neuromuscular features in sprinters with cerebral palsy: case studies based on
      paralympic classification.
AB  - Despite the evolution of runner performance in athletes with cerebral palsy (CP),
      little is known about neuromuscular parameters of sprinters from different
      classes, especially related to power output, muscular imbalances and asymmetry
      indexes in lower limbs. The aim of this study was to assess muscle power,
      muscular imbalance and asymmetry in sprinters with CP. Four male sprinters with
      CP (age, 18 to 27 years; body mass, 58.5 to 72.8 kg; height, 161.5 to 174 cm)
      classified as T38, T37, T36, T35 according to International Paralympic Committee
      functional classification, performed vertical counter movement jump and squat
      jump on force plate and isokinetic torque evaluations in both limbs. The
      concentric peak torque (PT) was measured at 60 degrees /sec, 120 degrees /sec and
      180 degrees /sec and PT eccentric at 60 degrees /sec and 120 degrees /sec. The
      asymmetry indexes, conventional and functional ratios were assessed. the results
      showed that athletes with more severe impairments (T35 and T36) showed worse
      performance to muscle power, more muscular imbalance and higher asymmetry in PT
      between limbs (> 10%). The exception was T37 athlete, who presented the better
      performance for all variables. it is concluded that CP athletes with more severe
      impairments showed lower jumping performance and torque production of knee
      extensors and flexors, they showed greater asymmetries between limbs. Finally,
      considering the results of T37 athlete, it seems that the athletic training for a
      longer period can reverse part of the neuromuscular impairments caused by CP.

PMID- 29326906
TI  - A comparison of ground reaction force components according to the foothold
      heights in 16-t truck during downward step.
AB  - The aim of this study is to compare and analyze the components of ground reaction
      force (GRF) relative to the foothold heights during downward step of 16-t truck.
      Adult males (n= 10) jumped downward from each 1st, 2nd, 3rd foothold step and
      driver's seat orderly using hand rail. Sampling rate of force components of 3
      axis (medial-lateral [ML] GRF, anterior-posterior [AP] GRF, peak vertical force
      [PVF]), variables (COPx, COPy, COP area) of center of pressure (COP), loading
      rate, and stability index (ML, AP, vertical, and dynamic postural stability index
      [DPSI]) processed from GRF system was cut off at 1,000 Hz. and variables was
      processed with repeated one-way analysis of variance. AP GRF, PVF and loading
      rate showed higher value in case of not used hand rail than that used hand rail
      in all 1st, 2nd, and 3rd of foothold step. DPSI showed more lowered stability in
      order of 2nd, 3rd step than 1st foothold step used with hand rail, of which
      showed lowest stability from driver's seat. COPx, COPy, and COP area showed
      higher value in case of 2nd and 3rd than that of 1st of foothold step, and showed
      lowest stability from driver's seat. It is more desirable for cargo truck driver
      to utilize an available hand rail in order of 3rd, 2nd, and 1st of foothold step
      than downward stepping directly, thus by which may results in decrease of falling
      injuries and minimization of impulsive force transferring to muscular-skeletal
      system.

PMID- 29326907
TI  - Remote Lifestyle Counseling Influences Cardiovascular Health Outcomes in Youth
      with Overweight or Obesity and Congenital Heart Disease.
AB  - Background: Children with overweight/obesity and congenital heart disease (CHD)
      are at increased cardiovascular risk. A lifestyle intervention may help reduce
      these risks. We sought to determine the feasibility of a smartphone-based
      lifestyle intervention to improve cardiovascular health outcomes in children with
      overweight/obesity and CHD. Methods: We examined the effect of bi-weekly
      nutrition and fitness counseling delivered via smartphone over 12 months. Thirty
      four youth, previously diagnosed with CHD and with overweight or obesity,
      participated in the intervention. They were divided into two groups depending on
      whether the heart disease required surgical correction (operated, n = 19) or not
      (non-operated, n = 15). Anthropometry, body composition cardiorespiratory
      exercise capacity, and cardio-metabolic risk factors were assessed at baseline, 6
      months, and 12 months. Results: Statistically significant decreases in waist
      circumference (WC), body mass index z-score, WC z-score, and waist to height
      ratio z-score were observed at 6 and 12 months in the operated group. A
      significant linear increase in lean body mass was observed in both groups. The
      study also had a high retention rate and a low attrition rate. Conclusion: The
      observed changes in anthropometry were positive with significant improvement to
      some cardiovascular and metabolic risk indicators. However, this was only
      observed in the operated group suggesting that other factors, such as perception
      of condition and self-efficacy, may influence lifestyle behaviors. The results
      from this pilot study clearly demonstrate the feasibility to perform a larger
      controlled study on remote lifestyle intervention in children with congenital
      heart defects and overweight or obesity.

PMID- 29326908
TI  - Asthma and Obesity in Children Are Independently Associated with Airway
      Dysanapsis.
AB  - Background: An increase in the prevalence of overweight and asthma has been
      observed. Both conditions affect negatively lung function in adults and children.
      The aim of this study was to analyze the effect of overweight and asthma on lung
      function in children. Methods: We designed a case-control study of healthy and
      asthmatic subjects nested within an epidemiological asthma prevalence study in
      children between 8 and 16 years of age. The effect of asthma and overweight on
      lung function was assessed by impulse oscillometry and spirometry obtained at
      baseline and 10-15 min after salbutamol. Results: 188 children were recruited,
      114 (61%) were asthmatics and 72 (38%) were overweight or obese. Children with
      asthma and overweight had a higher FVC (+1.16 z scores, p < 0.001) and higher
      FEV1 (+0.79 z scores, p = 0.004) and lower FEV1/FVC (-0.54 z scores, p = 0.008)
      when compared to healthy controls. Compared to normal weight asthmatics, the
      overweight had higher FVC (+0.78 z scores, p = 0.005) and lower FEV1/FVC (-0.50 z
      scores, p = 0.007). In the multivariate analysis, overweight was associated with
      an increase of 0.71 and 0.44 z scores in FVC and FEV1, respectively, and a
      reduction in FEV1/FVC by 0.40 z scores (p < 0.01 for all). Overweight had no
      effect on maximal flows and airway resistance at baseline, and this was not
      modified by inhalation of a bronchodilator. Asthma was also associated with
      higher post-BD FVC (0.45 z scores, p = 0.012) and FEV1 (0.35 z scores, p = 0.034)
      but not with FEV1/FVC and FEF25-75%. Two-way analysis of variance did not detect
      any interaction between asthma and overweight on lung function variables before
      or after bronchodilator. Conclusion: Our results suggest that asthma and
      overweight are independently associated with airway dysanaptic growth in children
      which can be further scrutinized using impulse oscillometry. Overweight
      contributed more to the reduction in FEV1/FVC than asthma in children without
      increasing airway resistance. Spirometry specificity and sensitivity for
      obstructive diseases may be reduced in populations with high prevalence of
      overweight. Adding impedance oscillometry to spirometry improves our
      understanding of the ventilatory abnormalities in overweight children.

PMID- 29326909
TI  - Association of Oxytocin and Parental Prefrontal Activation during Reunion with
      Infant: A Functional Near-Infrared Spectroscopy Study.
AB  - Although previous studies have revealed the role of oxytocin (OT) in parental
      behavior, the role of OT has not been investigated through the direct assessment
      of prefrontal brain activation during parenting. By using functional near
      infrared spectroscopy, we aimed to show the relationship between parental
      [maternal (N = 15) and paternal (N = 21)] OT levels and the activation of the
      prefrontal cortex (PFC), while holding their infants after separation. Baseline
      OT levels were measured in the subjects' saliva samples before the experiment.
      Prefrontal brain activation was assessed in participants sitting alone on a chair
      (i.e., separation from their infant for 120 s) and during the target period
      (i.e., holding their infant for 45 s), which was done in triplicate. The oxygen
      hemoglobin (oxy-Hb) dissociation curve significantly increased in 9 out of 22
      channels on the PFC when maternal and paternal samples were combined. However,
      only the fathers showed a correlation between salivary OT and oxy-Hb signal.
      Furthermore, while holding their infants, high-OT fathers showed left hemispheric
      dominance compared to low-OT fathers, while high-OT mothers showed right
      hemispheric dominance compared to low-OT mothers. This study showed that fathers
      with high-OT levels showed neural activation with left hemispheric dominance,
      while holding their infants, suggesting that increase of OT level might activate
      paternal PFC related to parenting behavior, although the same is not true for
      mothers.

PMID- 29326911
TI  - The Functional Evaluation of Eating Difficulties Scale: Study Protocol and
      Validation in Infants with Neurodevelopmental Impairments and Disabilities.
AB  - Introduction: A reliable and accurate evaluation of oral-motor skills in newborns
      at risk for swallowing and feeding disorders is key to set the goals of effective
      early interventions. Although many tools are available to assess oral-motor
      skills in newborns, limited evidence exists for what pertains their reliability
      and their effectivity in predicting short- and long-term developmental outcomes
      in at-risk infants. The aim of the present study is to develop and provide a
      preliminary validation of a new clinically grounded tool [i.e., the Functional
      Evaluation of Eating Difficulties Scale (FEEDS)] specifically designed to be used
      with at-risk newborns and infants. The paper describes the steps of tool
      development and information on the reliability of the tool are provided.
      Methods/analysis: The FEEDS has been developed according to clinical evidence and
      expertise by a multidisciplinary team of professionals dealing with feeding
      problems in at-risk infants diagnosed with neurodevelopmental impairments and
      disabilities. The steps of FEEDS development are reported, together with a
      detailed description of items, scoring procedure, and clinical cutoff. The FEEDS
      has been applied to a relatively large sample of 0- to 12-month-old infants (N =
      136) with neurodevelopmental disability, enrolled consecutively between 2004 and
      2016 at the Scientific Institute IRCCS Eugenio Medea (Bosisio Parini, Italy),
      which is the main rehabilitation hospital for children with neurodevelopmental
      disabilities in Italy. Internal consistency (Cronbach's alpha) and reliability
      (inter-rater agreement) have been assessed. Ethics and dissemination: All the
      procedures are consistent with the World Medical Association Declaration of
      Helsinki (2013) and the FEEDS has been approved by the clinical committee of the
      Scientific Institute IRCCS Eugenio Medea. Further psychometric characteristics
      and evidence of the predictive validity of the FEEDS will be obtained on a larger
      sample and they will be reported in future publications from this group.

PMID- 29326910
TI  - Is Autosomal Dominant Polycystic Kidney Disease Becoming a Pediatric Disorder?
AB  - Autosomal dominant polycystic kidney disease (ADPKD) affects 1 in 400 to 1,000
      live births, making it the most common monogenic cause of renal failure. Although
      no definite cure is available yet, it is important to affect disease progression
      by influencing modifiable factors such as hypertension and proteinuria. Besides
      this symptomatic management, the only drug currently recommended in Europe for
      selected adult patients with rapid disease progression, is the vasopressin
      receptor antagonist tolvaptan. However, the question remains whether these
      preventive interventions should be initiated before extensive renal damage has
      occurred. As renal cyst formation and expansion begins early in life, frequently
      in utero, ADPKD should no longer be considered an adult-onset disease. Moreover,
      the presence of hypertension and proteinuria in affected children has been
      reported to correlate well with disease severity. Until now, it is controversial
      whether children at-risk for ADPKD should be tested for the presence of the
      disease, and if so, how this should be done. Herein, we review the spectrum of
      pediatric ADPKD and discuss the pro and contra of testing at-risk children and
      the challenges and unmet needs in pediatric ADPKD care.

PMID- 29326912
TI  - Antenatal Consultation and Postnatal Stress in Mothers of Preterm Neonates (A Two
      Center Observational Case-Control Study).
AB  - Background: During antenatal consultation of women hospitalized for preterm
      labor, information of possible adverse outcomes is provided. This may however
      create additional maternal stress and raise some ethical concerns. Objective: The
      aim of the present study was to evaluate the influence of antenatal consultation
      by a neonatologist on maternal stress after delivery of a preterm infant admitted
      to NICU. Methods: In this study, secondary outcome parameters of a prospective
      two-center pilot observational study were analyzed. Mothers of preterm neonates <
      36 weeks of gestation admitted at two tertiary-level Neonatal-Intensive-Care
      Units (NICU) were included. Maternal stress was assessed with the Parental-Stress
      Scale:NICU (PSS:NICU) within 72 h after birth. PSS:NICU measures three scales:
      "relationship and parental role," "sights and sounds," and "baby looks and
      behaves." Maternal sociodemographic data were collected by questionnaire
      administered at the same time. Mothers who received antenatal neonatal
      consultation were matched for gestational age and compared to mothers who had no
      antenatal consultation by a neonatologist. Results: A total of 46 mothers of
      preterm neonates were included, 23 mothers in each group. There was no
      significant difference in sociodemographic data between the two groups regarding
      neonates and mothers. There were no significant differences between the two
      groups regarding stress scales of "sights and sounds" (2.00 +/- 0.76 versus 2.19
      +/- 0.79; p = 0.402), "looks and behaves" (2.55 +/- 0.90 versus 2.48 +/- 0.94; p
      = 0.732) and "relationship and parental role" (3.28 +/- 1.23 versus 3.46 +/-
      1.07; p = 0.517). Conclusion: Our study demonstrated that antenatal consultation
      by a neonatologist had no substantial influence on postnatal maternal stress in
      mothers of preterm neonates admitted to the NICU.

PMID- 29326914
TI  - Adolescents' Experiences and Their Suggestions for HIV Serostatus Disclosure in
      Zambia: A Mixed-Methods Study.
AB  - Background: HIV serostatus disclosure is an immense challenge for adolescents
      living with HIV, their caregivers, and health workers. In Zambia, however, little
      guidance is available from the adolescents' point of view on the HIV disclosure
      process. Objective: This study aimed to examine the setting of HIV serostatus
      disclosure for adolescents, its impacts on them, and their suggestions on the
      best practice of HIV disclosure. Methods: We conducted a mixed-methods study at
      the University Teaching Hospital in Zambia from April to July 2014. We recruited
      200 adolescents living with HIV, aged 15-19 years. We collected data using a
      structured questionnaire including two open-ended questions. We excluded two
      adolescents due to withdrawal during the survey, and eight from the data set due
      to out-of-eligibility criteria in age. Eventually, we included 190 in the
      analysis. We performed descriptive analysis to calculate the distributions of
      basic characteristics of the adolescents, their experience and preference on HIV
      serostatus disclosure, its emotional and behavioral impacts, and health education
      topics they had ever learned at hospital. We performed thematic analysis with
      open-ended data to explain first impressions upon disclosure in detail and to
      determine perceived advantages of HIV serostatus disclosure. Results: The
      majority of adolescents recommended the age of 12 as appropriate for adolescents
      to learn about their HIV serostatus and preferred disclosure by both parents. Out
      of 190 adolescents, 73.2% had negative or mixed feelings about HIV serostatus
      disclosure, while 86.2% reported that disclosure was beneficial. Thematic
      analyses showed that the adolescents reacted emotionally due to an unexpected
      disclosure and a belief of imminent death from HIV. However, they improved
      adherence to treatment (84.7%), limited self-disclosure of their HIV serostatus
      to others (81.1%), and felt more comfortable in talking about HIV with their
      caregivers (54.2%). Thematic analysis identified perceived benefits of disclosure
      as follows: better understanding of their sickness and treatment, and improved
      self-care and treatment adherence. Lower percentage of the adolescents have
      learned about psychosocial well-being, compared to facts about HIV and treatment.
      Conclusion: Despite initial emotional distress experienced after the disclosure,
      knowing one's own HIV serostatus was found to be a crucial turning point for
      adolescents to improve motivation for self-care. HIV serostatus disclosure to
      adolescents requires follow-up support involving parents/primary caregivers,
      health workers, and peers.

PMID- 29326913
TI  - The Genetic and Cellular Basis of Autosomal Dominant Polycystic Kidney Disease-A
      Primer for Clinicians.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common
      genetic disorders worldwide. In recent decades, the field has undergone a
      revolution, starting with the identification of causal ADPKD genes, including
      PKD1, PKD2, and the recently identified GANAB. In addition, advances defining the
      genetic mechanisms, protein localization and function, and the identification of
      numerous pathways involved in the disease process, have contributed to a better
      understanding of this illness. Together, this has led to a better prognosis,
      diagnosis, and treatment in clinical practice. In this mini review, we summarize
      and discuss new insights about the molecular mechanisms underlying ADPKD,
      including its genetics, protein function, and cellular pathways.

PMID- 29326915
TI  - Survival Mediterranean Style: Lifestyle Changes to Improve the Health of the US
      Fire Service.
AB  - Cardiovascular disease (CVD) causes almost half of all on-duty deaths in US
      firefighters and is an important and costly cause of morbidity. In addition,
      cancer is a growing health concern in this population. Obesity and obesity
      associated, cardiometabolic risk clustering are major, modifiable risk factors
      for fire service CVD and cancer risk. The Mediterranean diet (MedDiet) is proven
      effective in primary and secondary CVD prevention. It is also associated with a
      decreased risk of cancer and other chronic diseases. Moreover, it can be adapted
      into successful workplace interventions. Emerging data from our group regarding
      the US Fire Service show that greater compliance with the MedDiet is associated
      with improved CVD risk profiles and less weight gain among career firefighters.
      Moreover, the fact that career firefighters take a considerable number of meals
      communally on the job also represents an excellent opportunity for a workplace
      Mediterranean Diet Nutritional Intervention (MDNI). The devastating effects of
      obesity, CVD, and cancer on the US fire service are recognized, but currently few
      effective preventive programs exist. The consistently positive health benefits
      from following a MedDiet and promising preliminary data in the fire service
      justify translational research to determine the most effective means of
      delivering MDNIs to US firefighters. Therefore, a high priority should be
      assigned to efforts, which can help further disseminate and implement our program
      of novel behavior change strategies, "Survival Mediterranean Style," throughout
      the US fire service and eventually to other occupations.

PMID- 29326916
TI  - Development of the Social Network-Based Intervention "Powerful Together with
      Diabetes" Using Intervention Mapping.
AB  - This article describes the development of the social network-based intervention
      Powerful Together with Diabetes which aims to improve diabetes self-management
      (DSM) among patients with type 2 diabetes living in socioeconomically deprived
      neighborhoods by stimulating social support for DSM and diminishing social
      influences hindering DSM (e.g., peer pressure and social norms). The intervention
      was specifically developed for patients with Dutch, Turkish, Moroccan, and
      Surinamese backgrounds. The intervention was developed according to Intervention
      Mapping. This article describes the first four steps of Intervention Mapping: (1)
      the needs assessment; (2) development of performance and change objectives; (3)
      selection of theory-based methods and strategies; and (4) the translation of
      these into an organized program. These four steps resulted in Powerful Together
      with Diabetes, a 10-month group-based intervention consisting of 24 meetings, 6
      meetings for significant others, and 2 meetings for participants and their
      spouses. The IM method resulted in a tailored approach with a specific focus on
      the social networks of its participants. This article concludes that the IM
      method helped our planning team to tailor the intervention to the needs of our
      target population and facilitated our evaluation design. However, in hindsight,
      the intervention could have been improved by investing more in participatory
      planning and community involvement.

PMID- 29326918
TI  - "How Do We Start? And How Will They React?" Disclosing to Young People with
      Perinatally Acquired HIV in Uganda.
AB  - Despite great advances in pediatric HIV care, rates and the extent of full
      disclosure of HIV status to infected children remain low especially in resource
      constrained setting. The World Health Organisation recommends that, by the age of
      10-12 years old, children should be made fully aware of their HIV-positive
      status. However, this awareness is often delayed until much later in their
      adolescence. Few studies have been conducted to investigate what influences
      caregivers' decision-making process in this regard in low-income settings. In
      this article, we present an analysis of care dyads of caregivers and HIV-positive
      young people in Kampala, Uganda, as part of the findings of a longitudinal
      qualitative study about young people's adherence to antiretroviral therapy
      embedded in an international clinical trial (BREATHER). Repeat in-depth
      interviews were conducted with 26 young people living with HIV throughout the
      course of the trial, and once-off interviews with 16 of their caregivers were
      also carried out toward the end of the trial. In this article, we examine why and
      how caregivers decide to disclose a young person's HIV status to them and explore
      their feelings and dilemmas toward disclosure, as well as how young people
      reacted and the influence it had on their relationships with and attitudes toward
      their caregivers. Caregivers feared the consequences of disclosing the young
      person's positive status to them and disclosure commonly occurred hurriedly in
      response to a crisis, rather than as part of an anticipated and planned process.
      A key impediment to disclosure was that caregivers feared that disclosing would
      damage their relationships with the young people and commonly used this as a
      reason to continue to postpone disclosure. However, young people did not report
      prolonged feelings of blame or anger toward their caregivers about their own
      infection, but they did express frustration at the delay and obfuscation
      surrounding the disclosure process. Our findings can inform the ways in which
      mainstream HIV services support caregivers through the disclosure process. This
      includes providing positive encouragement to disclose fully and to be more
      confident in initiating and sustaining the timely process of disclosure.

PMID- 29326917
TI  - Baseline Preferences for Daily, Event-Driven, or Periodic HIV Pre-Exposure
      Prophylaxis among Gay and Bisexual Men in the PRELUDE Demonstration Project.
AB  - Introduction: The effectiveness of daily pre-exposure prophylaxis (PrEP) is well
      established. However, there has been increasing interest in non-daily dosing
      schedules among gay and bisexual men (GBM). This paper explores preferences for
      PrEP dosing schedules among GBM at baseline in the PRELUDE demonstration project.
      Materials and methods: Individuals at high-risk of HIV were enrolled in a free
      PrEP demonstration project in New South Wales, Australia, between November 2014
      and April 2016. At baseline, they completed an online survey containing detailed
      behavioural, demographic, and attitudinal questions, including their ideal way to
      take PrEP: daily (one pill taken every day), event-driven (pills taken only
      around specific risk events), or periodic (daily dosing during periods of
      increased risk). Results: Overall, 315 GBM (98% of study sample) provided a
      preferred PrEP dosing schedule at baseline. One-third of GBM expressed a
      preference for non-daily PrEP dosing: 20% for event-driven PrEP, and 14% for
      periodic PrEP. Individuals with a trade/vocational qualification were more likely
      to prefer periodic to daily PrEP [adjusted odds ratio (aOR) = 4.58, 95%
      confidence intervals (95% CI): (1.68, 12.49)], compared to individuals whose
      highest level of education was high school. Having an HIV-positive main regular
      partner was associated with strong preference for daily, compared to event-driven
      PrEP [aOR = 0.20, 95% CI: (0.04, 0.87)]. Participants who rated themselves better
      at taking medications were more likely to prefer daily over periodic PrEP [aOR =
      0.39, 95% CI: (0.20, 0.76)]. Discussion: Individuals' preferences for PrEP
      schedules are associated with demographic and behavioural factors that may impact
      on their ability to access health services and information about PrEP and
      patterns of HIV risk. At the time of data collection, there were limited data
      available about the efficacy of non-daily PrEP schedules, and clinicians only
      recommended daily PrEP to study participants. Further research investigating how
      behaviours and PrEP preferences change correspondingly over time is needed. Trial
      registration: ClinicalTrials.gov NCT02206555. Registered 28 July 2014.

PMID- 29326919
TI  - Exposure Assessment and Biomonitoring of Workers in Magnetic Resonance
      Environment: An Exploratory Study.
AB  - Magnetic resonance imaging (MRI) has evolved rapidly over the past few decades as
      one of the most flexible tools in medical research and diagnostic imaging. MRI
      facilities are important sources of multiple exposure to electromagnetic fields
      for both patients and health-care staff, due to the presence of electromagnetic
      fields of multiple frequency ranges, different temporal variations, and field
      strengths. Due to the increasing use and technological advancements of MRI
      systems, clearer insights into exposure assessment and a better understanding of
      possible harmful effects due to long-term exposures are highly needed. In the
      present exploratory study, exposure assessment and biomonitoring of MRI workers
      at the Radio-diagnostics Unit of the National Cancer Institute of Naples "Pascale
      Foundation" (Naples, Italy) have been carried out. In particular, exposure to the
      MRI static magnetic field (SMF) has been evaluated by means of personal
      monitoring, while an application tool has been developed to provide an estimate
      of motion-induced, time-varying electric fields. Measurement results have
      highlighted a high day-to-day and worker-to-worker variability of the exposure to
      the SMF, which strongly depends on the characteristics of the environment and on
      personal behaviors, and the developed application tool can be adopted as an easy
      to-use tool for rapid and qualitative evaluation of motion-induced, time-varying
      electric field exposure. Regarding biomonitoring, the 24 workers of the Radio
      diagnostics Unit were enrolled to evaluate both spontaneous and mitomycin C
      induced chromosomal fragility in human peripheral blood lymphocytes, by means of
      the cytokinesis-block micronucleus assay. The study subjects were 12 MRI workers,
      representative of different professional categories, as the exposed group, and 12
      workers with no MRI exposure history, as the reference group. The results show a
      high worker-to-worker variability for both field exposure assessment and
      biomonitoring, as well as several critical issues and practicalities to be faced
      with in this type of investigations. The procedures for risk assessment and
      biomonitoring proposed here can be used to inform future research in this field,
      which will require a refinement of exposure assessment methods and an enlargement
      of the number of subjects enrolled in the biomonitoring study to gain robust
      statistics and reliable results.

PMID- 29326920
TI  - The Diabetes Management Education Program in South Texas: An Economic and
      Clinical Impact Analysis.
AB  - Introduction: Diabetes is a major chronic disease that can lead to serious health
      problems and high healthcare costs without appropriate disease management and
      treatment. In the United States, the number of people diagnosed with diabetes and
      the cost for diabetes treatment has dramatically increased over time. To improve
      patients' self-management skills and clinical outcomes, diabetes management
      education (DME) programs have been developed and operated in various regions.
      Objective: This community case study explores and calculates the economic and
      clinical impacts of expanding a model DME program into 26 counties located in
      South Texas. Methods: The study sample includes 355 patients with type 2 diabetes
      and a follow-up hemoglobin A1c level measurement among 1,275 individuals who
      participated in the DME program between September 2012 and August 2013. We used
      the Gilmer's cost differentials model and the United Kingdom Prospective Diabetes
      Study (UKPDS) Risk Engine methodology to predict 3-year healthcare cost savings
      and 10-year clinical benefits of implementing a DME program in the selected 26
      Texas counties. Results: Changes in estimated 3-year cost and the estimated
      treatment effect were based on baseline hemoglobin A1c level. An average 3-year
      reduction in medical treatment costs per program participant was $2,033 (in 2016
      dollars). The total healthcare cost savings for the 26 targeted counties
      increases as the program participation rate increases. The total projected cost
      saving ranges from $12 million with 5% participation rate to $185 million with
      75% participation rate. A 10-year outlook on additional clinical benefits
      associated with the implementation and expansion of the DME program at 60%
      participation is estimated to result in approximately 4,838 avoided coronary
      heart disease cases and another 392 cases of avoided strokes. Conclusion: The
      implementation of this model DME program in the selected 26 counties would
      contribute to substantial healthcare cost savings and clinical benefits.
      Organizations that provide DME services may benefit from reduction in medical
      treatment costs and improvement in clinical outcomes for populations with
      diabetes.

PMID- 29326921
TI  - Survey on the Use of Whole-Genome Sequencing for Infectious Diseases
      Surveillance: Rapid Expansion of European National Capacities, 2015-2016.
AB  - Whole-genome sequencing (WGS) has become an essential tool for public health
      surveillance and molecular epidemiology of infectious diseases and antimicrobial
      drug resistance. It provides precise geographical delineation of spread and
      enables incidence monitoring of pathogens at genotype level. Coupled with
      epidemiological and environmental investigations, it delivers ultimate resolution
      for tracing sources of epidemic infections. To ascertain the level of
      implementation of WGS-based typing for national public health surveillance and
      investigation of prioritized diseases in the European Union (EU)/European
      Economic Area (EEA), two surveys were conducted in 2015 and 2016. The surveys
      were designed to determine the national public health reference laboratories'
      access to WGS and operational WGS-based typing capacity for national surveillance
      of selected foodborne pathogens, antimicrobial-resistant pathogens, and vaccine
      preventable diseases identified as priorities for European genomic surveillance.
      Twenty-eight and twenty-nine out of the 30 EU/EEA countries participated in the
      survey in 2015 and 2016, respectively. National public health reference
      laboratories in 22 and 25 countries had access to WGS-based typing for public
      health applications in 2015 and 2016, respectively. Reported reasons for limited
      or no access were lack of funding, staff, and expertise. Illumina technology was
      the most frequently used followed by Ion Torrent technology. The access to
      bioinformatics expertise and competence for routine WGS data analysis was
      limited. By mid-2016, half of the EU/EEA countries were using WGS analysis either
      as first- or second-line typing method for surveillance of the pathogens and
      antibiotic resistance issues identified as EU priorities. The sampling frame as
      well as bioinformatics analysis varied by pathogen/resistance issue and country.
      Core genome multilocus allelic profiling, also called cgMLST, was the most
      frequently used annotation approach for typing bacterial genomes suggesting
      potential bioinformatics pipeline compatibility. Further capacity development for
      WGS-based typing is ongoing in many countries and upon consolidation and
      harmonization of methods should enable pan-EU data exchange for genomic
      surveillance in the medium-term subject to the development of suitable data
      management systems and appropriate agreements for data sharing.

PMID- 29326922
TI  - Patterns and Gaps Identified in a Systematic Review of the Hepatitis C Virus Care
      Continuum in Studies among People Who Use Drugs.
AB  - Introduction: Systematic reviews are useful for synthesizing data on various
      health conditions and for identifying gaps in available data. In the US, the main
      risk group for hepatitis C virus (HCV) infection is people who use drugs (PWUD);
      as a group, PWUD have the highest prevalence of chronic HCV. While the care
      continuum construct has been increasingly applied to studies of HCV care among
      PWUD, what constitutes the steps in an HCV care continuum is not standardized. We
      sought to examine the range of HCV care continuum outcomes that studies reported
      on, to identify gaps in the literature, and to develop strategies that allowed
      for valuable syntheses of care continuum data. Methods: We conducted searches of
      electronic databases for published literature. Reports were eligible if they
      provided original data from 1990 to 2016 from the US, presented data on one or
      more HCV care continuum outcomes, and provided outcome data on PWUD as a distinct
      group. Results: A total of 313 full-text reports were assessed for eligibility.
      Of 212 potentially eligible reports, 32 (15.1%) did not present outcomes for PWUD
      separately from those who were non-PWUD. Among 101 eligible reports, a total of
      166 care continuum outcomes were extracted; outcomes could be grouped into three
      categories that represent the HCV care continuum: testing (39.8%, n = 66/166);
      linkage to care (16.9%, n = 28/166); and treatment (43.4%, n = 72/166). Seventy
      four reports (73.3%, n = 74/101) presented data on only one step. Linkage to care
      occurred variably after only antibody, or after antibody and viral load (VL)
      testing. Six (5.9%, n = 6/101) reports presented data on all three steps.
      Conclusion: Reports examined a variety of HCV care continuum outcomes that could
      be grouped into the three steps of testing, linkage to care, and treatment. The
      application of this care continuum model would facilitate subsequent data
      synthesis for program comparison and public health evaluation. Given the two-step
      nature of HCV testing, analyses also need to account for variation in whether
      linkage to care occurred after antibody testing or after sequential antibody and
      VL testing. Additional data are needed on the progression of PWUD through the
      entire care continuum.

PMID- 29326924
TI  - Influence of the Chemical Structure on Odor Qualities and Odor Thresholds of
      Halogenated Guaiacol-Derived Odorants.
AB  - Chlorinated guaiacol derivatives are found in waste water of pulp mills using
      chlorine in the bleaching process of wood pulp. They can also be detected in fish
      tissue, possibly causing off-odors. To date, there is no systematic investigation
      on the odor properties of halogenated guaiacol derivatives. To close this gap,
      odor thresholds in air and odor qualities of 14 compounds were determined by gas
      chromatography-olfactometry. Overall, the investigated compounds elicited smells
      that are characteristic for guaiacol, namely smoky, sweet, vanilla-like, but also
      medicinal and plaster-like. Their odor thresholds in air were, however, very low,
      ranging from 0.00072 to 23 ng/Lair. The lowest thresholds were found for 5-chloro
      and 5-bromoguaiacol, followed by 4,5-dichloro- and 6-chloroguaiacol. Moreover,
      some inter-individual differences in odor threshold values could be observed,
      with the highest variations having been recorded for the individual values of 5
      iodo- and 4-bromoguaiacol.

PMID- 29326923
TI  - Inorganic Nanocrystals Functionalized Mesoporous Silica Nanoparticles:
      Fabrication and Enhanced Bio-applications.
AB  - Mesoporous SiO2 nanoparticles (MSNs) are one of the most promising materials for
      bio-related applications due to advantages such as good biocompatibility, tunable
      mesopores, and large pore volume. However, unlike the inorganic nanocrystals with
      abundant physical properties, MSNs alone lack functional features. Thus, they are
      not sufficiently suitable for bio-applications that require special functions.
      Consequently, MSNs are often functionalized by incorporating inorganic
      nanocrystals, which provide a wide range of intriguing properties. This review
      focuses on inorganic nanocrystals functionalized MSNs, both their fabrication and
      bio-applications. Some of the most utilized methods for coating mesoporous silica
      (mSiO2) on nanoparticles were summarized. Magnetic, fluorescence and photothermal
      inorganic nanocrystals functionalized MSNs were taken as examples to demonstrate
      the bio-applications. Furthermore, asymmetry of MSNs and their effects on
      functions were also highlighted.

PMID- 29326925
TI  - Photodegradation of Rhodamine B over Biomass-Derived Activated Carbon Supported
      CdS Nanomaterials under Visible Irradiation.
AB  - A family of new composite materials was successfully prepared through the
      deposition of as-synthesized CdS nanomaterials on lotus-seedpod-derived activated
      carbon (SAC). The SAC supports derived at different activation temperatures
      exhibited considerably large surface areas and various microstructures that were
      of great importance in enhancing photocatalytic performance of CdS@SAC composite
      materials toward the photodegradation of rhodamine B (RhB) under visible
      irradiation. The best-performing CdS@SAC-800 showed excellent photocatalytic
      activity with a rate constant of ca. 2.40 * 10-2 min-1, which was approximately
      13 times higher than that of the CdS nanomaterials. Moreover, the estimated band
      gap energy of CdS@SAC-800 was significantly lowered down to 1.99 eV compared to
      that of the CdS precursor (2.22 eV), which suggested considerable strength of
      interface contact between the CdS and SAC support, as well as efficient light
      harvesting capacity of the composite material. Further photocatalytic study
      indicated that the SAC supports enhanced the separation of photogenerated
      electrons and holes in this system. Improved photocatalytic activity of the
      composite materials was largely due to the increased generation of catalytically
      active species such as h+, OH*, [Formula: see text] etc. This work provided a
      facile and low-cost pathway to fabricate photocatalysts for viable degradation of
      organic dye molecules.

PMID- 29326926
TI  - Neuromechanical Cost Functionals Governing Motor Control for Early Screening of
      Motor Disorders.
AB  - Developing a quantifier of the neural control of motion is extremely useful in
      characterizing motor disorders and personalizing the model equations using data.
      We approach this problem using a top-down optimal control methodology, with an
      aim that the quantity estimated from the collected data is representative of the
      underlying neural controller. For this purpose, we assume that during the flexion
      of an arm, human brain optimizes a functional. A functional is defined as a
      function of a function that returns a scalar. Generally, in forward problems,
      this functional is chosen to be a function of metabolic energy spent, jerkiness,
      variance of motion, etc., integrated throughout the trajectory of motion. Current
      states (angular configuration and velocity) and torque applied can approximately
      determine the motion of a joint. Therefore, any internal cost functional
      optimized by the brain has to have its effect in the control of the torque. In
      this work, we study the flexion of the arm in normals and patient groups and
      intend to find the cost functionals governing the motion. To achieve this, we
      parametrize the cost functional governing the motion into the variables thetap
      and omegap , which are then estimated using marker data obtained from the
      subjects. These parameters are shown to vary significantly for the normal and
      patient populations. The thetap values were shown to be significantly higher in
      the case of patients than in the case of normals and omegap values showed an
      exactly opposite trend. We also studied how these cost functionals govern the
      applied torques in both subject groups and how is it affected while perturbed
      with sinusoidal frequencies. A time frequency analysis of the resulting solutions
      revealed a distinguishing pattern for the normals compared with the patient
      groups.

PMID- 29326927
TI  - Nanoparticles-Emerging Potential for Managing Leukemia and Lymphoma.
AB  - Nanotechnology has become a powerful approach to improve the way we diagnose and
      treat cancer. In particular, nanoparticles (NPs) possess unique features for
      enhanced sensitivity and selectivity for earlier detection of circulating cancer
      biomarkers. In vivo, NPs enhance the therapeutic efficacy of anticancer agents
      when compared with conventional chemotherapy, improving vectorization and
      delivery, and helping to overcome drug resistance. Nanomedicine has been mostly
      focused on solid cancers due to take advantage from the enhanced permeability and
      retention (EPR) effect experienced by tissues in the close vicinity of tumors,
      which enhance nanomedicine's accumulation and, consequently, improve efficacy.
      Nanomedicines for leukemia and lymphoma, where EPR effect is not a factor, are
      addressed differently from solid tumors. Nevertheless, NPs have provided
      innovative approaches to simple and non-invasive methodologies for diagnosis and
      treatment in liquid tumors. In this review, we consider the state of the art on
      different types of nanoconstructs for the management of liquid tumors, from
      preclinical studies to clinical trials. We also discuss the advantages of
      nanoplatforms for theranostics and the central role played by NPs in this
      combined strategy.

PMID- 29326929
TI  - Improvement of Xylose Fermentation Ability under Heat and Acid Co-Stress in
      Saccharomyces cerevisiae Using Genome Shuffling Technique.
AB  - Xylose-assimilating yeasts with tolerance to both fermentation inhibitors (such
      as weak organic acids) and high temperature are required for cost-effective
      simultaneous saccharification and cofermentation (SSCF) of lignocellulosic
      materials. Here, we demonstrate the construction of a novel xylose-utilizing
      Saccharomyces cerevisiae strain with improved fermentation ability under heat and
      acid co-stress using the drug resistance marker-aided genome shuffling technique.
      The mutagenized genome pools derived from xylose-utilizing diploid yeasts with
      thermotolerance or acid tolerance were shuffled by sporulation and mating. The
      shuffled strains were then subjected to screening under co-stress conditions of
      heat and acids, and the hybrid strain Hyb-8 was isolated. The hybrid strain
      displayed enhanced xylose fermentation ability in comparison to both parental
      strains under co-stress conditions of heat and acids. Hyb-8 consumed 33.1 +/- 0.6
      g/L xylose and produced 11.1 +/- 0.4 g/L ethanol after 72 h of fermentation at 38
      degrees C with 20 mM acetic acid and 15 mM formic acid. We also performed
      transcriptomic analysis of the hybrid strain and its parental strains to screen
      for key genes for multiple stress tolerances. We found that 13 genes, including 5
      associated with cellular transition metal ion homeostasis, were significantly
      upregulated in Hyb-8 compared to levels in both parental strains under co-stress
      conditions. The hybrid strain Hyb-8 has strong potential for cost-effective SSCF
      of lignocellulosic materials. Moreover, the transcriptome data gathered in this
      study will be useful for understanding the mechanisms of multiple tolerance to
      high temperature and acids in yeast and facilitate the development of robust
      yeast strains for SSCF.

PMID- 29326928
TI  - Smart Materials Meet Multifunctional Biomedical Devices: Current and Prospective
      Implications for Nanomedicine.
AB  - With the increasing advances in the fabrication and in monitoring approaches of
      nanotechnology devices, novel materials are being synthesized and tested for the
      interaction with biological environments. Among them, smart materials in
      particular provide versatile and dynamically tunable platforms for the
      investigation and manipulation of several biological activities with very low
      invasiveness in hardly accessible anatomical districts. In the following, we will
      briefly recall recent examples of nanotechnology-based materials that can be
      remotely activated and controlled through different sources of energy, such as
      electromagnetic fields or ultrasounds, for their relevance to both basic science
      investigations and translational nanomedicine. Moreover, we will introduce some
      examples of hybrid materials showing mutually beneficial components for the
      development of multifunctional devices, able to simultaneously perform duties
      like imaging, tissue targeting, drug delivery, and redox state control. Finally,
      we will highlight challenging perspectives for the development of theranostic
      agents (merging diagnostic and therapeutic functionalities), underlining open
      questions for these smart nanotechnology-based devices to be made readily
      available to the patients in need.

PMID- 29326931
TI  - Editorial: Molecular Organization of Membranes: Where Biology Meets Biophysics.

PMID- 29326932
TI  - Editorial: Determinants of Cell Size.

PMID- 29326930
TI  - RUNX1 Mutations in Inherited and Sporadic Leukemia.
AB  - RUNX1 is a recurrently mutated gene in sporadic myelodysplastic syndrome and
      leukemia. Inherited mutations in RUNX1 cause familial platelet disorder with
      predisposition to acute myeloid leukemia (FPD/AML). In sporadic AML, mutations in
      RUNX1 are usually secondary events, whereas in FPD/AML they are initiating
      events. Here we will describe mutations in RUNX1 in sporadic AML and in FPD/AML,
      discuss the mechanisms by which inherited mutations in RUNX1 could elevate the
      risk of AML in FPD/AML individuals, and speculate on why mutations in RUNX1 are
      rarely, if ever, the first event in sporadic AML.

PMID- 29326933
TI  - Perioperative Management of a Patient with Cold Urticaria.
AB  - Cold urticaria consists of an allergic immune response to cold temperatures with
      symptoms ranging from pruritic wheals to life-threatening angioedema,
      bronchospasm, or anaphylactic shock. Adequate planning to maintain normothermia
      perioperatively is vital due to impaired hypothalamic thermoregulation and
      overall depression of sympathetic outflow during deep sedation and general
      anesthesia. This case report describes the successful perioperative management of
      a 45-year-old female with a history of cold urticaria undergoing a laparoscopic
      Nissen fundoplication for refractory gastroesophageal reflux disease and
      discusses how to appropriately optimize the care of these patients.

PMID- 29326934
TI  - Exploring the Link between Uric Acid and Osteoarthritis.
AB  - Both gout and osteoarthritis (OA) are common forms of arthritis that inflict a
      huge burden to an aging population with the increasing prevalence of obesity.
      Clinicians have long observed the link between these two conditions. In this
      review, we summarize the evidence from epidemiologic and immunological studies
      that described the possible relationship between the two conditions. The recent
      new understanding on monosodium uric acid crystal-induced inflammation has given
      insight into probable shared pathogenesis pathways for both conditions. We
      describe the potential therapeutic implications, particularly regarding the
      possibility of repurposing traditional gout medications for use in OA.

PMID- 29326935
TI  - Integrating Patient Perspectives into Personalized Medicine in Idiopathic
      Pulmonary Fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal disease
      which has a major impact on patients' quality of life (QOL). Except for lung
      transplantation, there is no curative treatment option. Fortunately, two disease
      modifying drugs that slow down disease decline were recently approved. Though
      this is a major step forward, these drugs do not halt or reverse the disease, nor
      convincingly improve health-related QOL. In daily practice, disease behavior and
      response to therapy greatly vary among patients. It is assumed that this is
      related to the multiple biological pathways and complex interactions between
      genetic, molecular, and environmental factors that are involved in the
      pathogenesis of IPF. Recently, research in IPF has therefore started to focus on
      developing targeted therapy through identifying genetic risk factors and
      biomarkers. In this rapidly evolving field of personalized medicine, patient
      factors such as lifestyle, comorbidities, preferences, and experiences with
      medication should not be overlooked. This review describes recent insights and
      methods on how to integrate patient perspectives into personalized medicine.
      Furthermore, it provides an overview of the most used patient-reported outcome
      measures in IPF, to facilitate choices for both researchers and clinicians when
      incorporating the patient voice in their research and care. To enhance truly
      personalized treatment in IPF, biology should be combined with patient
      perspectives.

PMID- 29326936
TI  - Characterisation of Physical Frailty and Associated Physical and Functional
      Impairments in Mild Cognitive Impairment.
AB  - Objective: To characterize the physical frailty phenotype and its associated
      physical and functional impairments in mild cognitive impairment (MCI). Method:
      Participants with MCI (N = 119), normal low cognition (NLC, N = 138), and normal
      high cognition (NHC, N = 1,681) in the Singapore Longitudinal Ageing Studies
      (SLAS-2) were compared on the prevalence of physical frailty, low lean body mass,
      weakness, slow gait, exhaustion and low physical activity, and POMA balance and
      gait impairment and fall risk. Results: There were significantly higher
      prevalence of frailty in MCI (18.5%), than in NLC (8.0%) and NHC (3.9%), and pre
      frailty in MCI (54.6%), NLC (52.9%) than in NHC (48.0%). Age, sex, and ethnicity
      adjusted OR (95% CI) of association with MCI (versus NHC) for frailty were 4.65
      (2.40-9.04) and for pre-frailty, 1.67 (1.07-2.61). Similar significantly elevated
      prevalence and adjusted ORs of association with MCI were observed for frailty
      associated physical and functional impairments. Further adjustment for education,
      marital status, living status, comorbidities, and GDS significantly reduced the
      OR estimates. However, the OR estimates remained elevated for frailty: 3.86 (1.83
      8.17), low body mass: 1.70 (1.08-2.67), slow gait: 1.84 (1.17-2.89), impaired
      gait: 4.17 (1.98-8.81), and elevated fall risk 3.42 (1.22-9.53). Conclusion: Two
      thirds of MCI were physically frail or pre-frail, most uniquely due to low lean
      muscle mass, slow gait speed, or balance and gait impairment. The close
      associations of frailty and physical and functional impairment with MCI have
      important implications for improving diagnostic acuity of MCI and targetting
      interventions among cognitively frail individuals to prevent dementia and
      disability.

PMID- 29326937
TI  - Removal of the C-Terminal Domains of ADAMTS13 by Activated Coagulation Factor XI
      induces Platelet Adhesion on Endothelial Cells under Flow Conditions.
AB  - Platelet recruitment to sites of vascular injury is mediated by von Willebrand
      factor (VWF). The shear-induced unraveling of ultra-large VWF multimers causes
      the formation of a "stringlike" conformation, which rapidly recruits platelets
      from the bloodstream. A disintegrin and metalloproteinase with a thrombospondin
      type 1 motif, member 13 (ADAMTS13) regulates this process by cleaving VWF to
      prevent aberrant platelet adhesion; it is unclear whether the activity of
      ADAMTS13 itself is regulated. The serine proteases alpha-thrombin and plasmin
      have been shown to cleave ADAMTS13. Based on sequence homology, we hypothesized
      that activated coagulation factor XI (FXIa) would likewise cleave ADAMTS13. Our
      results show that FXIa cleaves ADAMTS13 at the C-terminal domains, generating a
      truncated ADAMTS13 with a deletion of part of the thrombospondin type-1 domain
      and the CUB1-2 domains, while alpha-thrombin cleaves ADAMTS13 near the CUB1-2
      domains and plasmin cleaves ADAMTS13 at the metalloprotease domain and at the C
      terminal domain. Using a cell surface immunoassay, we observed that FXIa induced
      the deletion of the CUB1-2 domains from ADAMTS13 on the surface of endothelial
      cells. Removal of the C-terminal domain of ADAMTS13 by FXIa or alpha-thrombin
      caused an increase in ADAMTS13 activity as measured by a fluorogenic substrate
      (FRETS) and blocked the ability of ADAMTS13 to cleave VWF on the endothelial cell
      surface, resulting in persistence of VWF strands and causing an increase in
      platelet adhesion under flow conditions. We have demonstrated a novel mechanism
      for coagulation proteinases including FXIa in regulating ADAMTS13 activity and
      function. This may represent an additional hemostatic function by which FXIa
      promotes local platelet deposition at sites of vessel injury.

PMID- 29326938
TI  - Key Triggers of Osteoclast-Related Diseases and Available Strategies for Targeted
      Therapies: A Review.
AB  - Osteoclasts, the only cells with bone resorption functions in vivo, maintain the
      balance of bone metabolism by cooperating with osteoblasts, which are responsible
      for bone formation. Excessive activity of osteoclasts causes many diseases such
      as osteoporosis, periprosthetic osteolysis, bone tumors, and Paget's disease. In
      contrast, osteopetrosis results from osteoclast deficiency. Available strategies
      for combating over-activated osteoclasts and the subsequently induced diseases
      can be categorized into three approaches: facilitating osteoclast apoptosis,
      inhibiting osteoclastogenesis, and impairing bone resorption. Bisphosphonates are
      representative molecules that function by triggering osteoclast apoptosis. New
      drugs, such as tumor necrosis factor and receptor activator of nuclear factor
      kappa-B ligand (RANKL) inhibitors (e.g., denosumab) have been developed for
      targeting the receptor activator of nuclear factor kappa-B /RANKL/osteoprotegerin
      system or CSF-1/CSF-1R axis, which play critical roles in osteoclast formation.
      Furthermore, vacuolar (H+)-ATPase inhibitors, cathepsin K inhibitors, and
      glucagon-like peptide 2 impair different stages of the bone resorption process.
      Recently, significant achievements have been made in this field. The aim of this
      review is to provide an updated summary of the current progress in research
      involving osteoclast-related diseases and of the development of targeted
      inhibitors of osteoclast formation.

PMID- 29326939
TI  - The Amide Local Anesthetic Lidocaine in Cancer Surgery-Potential Antimetastatic
      Effects and Preservation of Immune Cell Function? A Narrative Review.
AB  - Surgical removal of the primary tumor in solid cancer is an essential component
      of the treatment. However, the perioperative period can paradoxically lead to an
      increased risk of cancer recurrence. A bimodal dynamics for early-stage breast
      cancer recurrence suggests a tumor dormancy-based model with a mastectomy-driven
      acceleration of the metastatic process and a crucial role of the
      immunosuppressive state during the perioperative period. Recent evidence suggests
      that anesthesia could also influence the progress of the disease. Local
      anesthetics (LAs) have long been used for their properties to block nociceptive
      input. They also exert anti-inflammatory capacities by modulating the liberation
      or signal propagation of inflammatory mediators. Interestingly, LAs can reduce
      viability and proliferation of many cancer cells in vitro as well. Additionally,
      retrospective clinical trials have suggested that regional anesthesia for cancer
      surgery (either with or without general anesthesia) might reduce the risk of
      recurrence. Lidocaine, a LA, which can be administered intravenously, is widely
      used in clinical practice for multimodal analgesia. It is associated with a
      morphine-sparing effect, reduced pain scores, and in major surgery probably also
      with a reduced incidence of postoperative ileus and length of hospital stay.
      Systemic delivery might therefore be efficient to target residual disease or
      reach cells able to form micrometastasis. Moreover, an in vitro study has shown
      that lidocaine could enhance the activity of natural killer (NK) cells. Due to
      their ability to recognize and kill tumor cells without the requirement of prior
      antigen exposure, NKs are the main actor of the innate immune system. However,
      several perioperative factors can reduce NK activity, such as stress, pain,
      opioids, or general anesthetics. Intravenous lidocaine as part of the
      perioperative anesthesia regimen would be of major interest for clinicians, as it
      might bear the potential to reduce the risk of cancer recurrence or progression
      patients undergoing cancer surgery. As a well-known pharmaceutical agent,
      lidocaine might therefore be a promising candidate for oncological drug
      repurposing. We urgently need clinical randomized trials assessing the protective
      effect of lidocaine on NKs function and against recurrence after cancer surgery
      to achieve a "proof of concept."

PMID- 29326941
TI  - Structural Validation of a French Food Frequency Questionnaire of 94 Items.
AB  - Background: Food frequency questionnaires (FFQs) are used to estimate the usual
      food and nutrient intakes over a period of time. Such estimates can suffer from
      measurement errors, either due to bias induced by respondent's answers or to
      errors induced by the structure of the questionnaire (e.g., using a limited
      number of food items and an aggregated food database with average portion sizes).
      The "structural validation" presented in this study aims to isolate and quantify
      the impact of the inherent structure of a FFQ on the estimation of food and
      nutrient intakes, independently of respondent's perception of the questionnaire.
      Methods: A semi-quantitative FFQ (n = 94 items, including 50 items with questions
      on portion sizes) and an associated aggregated food composition database (named
      the item-composition database) were developed, based on the self-reported weekly
      dietary records of 1918 adults (18-79 years-old) in the French Individual and
      National Dietary Survey 2 (INCA2), and the French CIQUAL 2013 food-composition
      database of all the foods (n = 1342 foods) declared as consumed in the
      population. Reference intakes of foods ("REF_FOOD") and nutrients ("REF_NUT")
      were calculated for each adult using the food-composition database and the
      amounts of foods self-reported in his/her dietary record. Then, answers to the
      FFQ were simulated for each adult based on his/her self-reported dietary record.
      "FFQ_FOOD" and "FFQ_NUT" intakes were estimated using the simulated answers and
      the item-composition database. Measurement errors (in %), spearman correlations
      and cross-classification were used to compare "REF_FOOD" with "FFQ_FOOD" and
      "REF_NUT" with "FFQ_NUT". Results: Compared to "REF_NUT," "FFQ_NUT" total
      quantity and total energy intake were underestimated on average by 198 g/day and
      666 kJ/day, respectively. "FFQ_FOOD" intakes were well estimated for starches,
      underestimated for most of the subgroups, and overestimated for some subgroups,
      in particular vegetables. Underestimation were mainly due to the use of portion
      sizes, leading to an underestimation of most of nutrients, except free sugars
      which were overestimated. Conclusion: The "structural validation" by simulating
      answers to a FFQ based on a reference dietary survey is innovative and pragmatic
      and allows quantifying the error induced by the simplification of the method of
      collection.

PMID- 29326940
TI  - Flavonoids from Engineered Tomatoes Inhibit Gut Barrier Pro-inflammatory
      Cytokines and Chemokines, via SAPK/JNK and p38 MAPK Pathways.
AB  - Flavonoids are a diverse group of plant secondary metabolites, known to reduce
      inflammatory bowel disease symptoms. How they achieve this is largely unknown.
      Our study focuses on the gut epithelium as it receives high topological doses of
      dietary constituents, maintains gut homeostasis, and orchestrates gut immunity.
      Dysregulation leads to chronic gut inflammation, via dendritic cell (DC)-driven
      immune responses. Tomatoes engineered for enriched sets of flavonoids
      (anthocyanins or flavonols) provided a unique and complex naturally consumed food
      matrix to study the effect of diet on chronic inflammation. Primary murine
      colonic epithelial cell-based inflammation assays consist of chemokine induction,
      apoptosis and proliferation, and effects on kinase pathways. Primary murine
      leukocytes and DCs were used to assay effects on transmigration. A murine
      intestinal cell line was used to assay wound healing. Engineered tomato extracts
      (enriched in anthocyanins or flavonols) showed strong and specific inhibitory
      effects on a set of key epithelial pro-inflammatory cytokines and chemokines.
      Chemotaxis assays showed a resulting reduction in the migration of primary
      leukocytes and DCs. Activation of epithelial cell SAPK/JNK and p38 MAPK signaling
      pathways were specifically inhibited. The epithelial wound healing-associated
      STAT3 pathway was unaffected. Cellular migration, proliferation, and apoptosis
      assays confirmed that wound healing processes were not affected by flavonoids. We
      show flavonoids target epithelial pro-inflammatory kinase pathways, inhibiting
      chemotactic signals resulting in reduced leukocyte and DC chemotaxis. Thus, both
      anthocyanins and flavonols modulate epithelial cells to become hyporesponsive to
      bacterial stimulation. Our results identify a viable mechanism to explain the in
      vivo anti-inflammatory effects of flavonoids.

PMID- 29326943
TI  - Pseudomyxoma Peritonei: A Case Report Diagnosed in a 47-Year-Old Woman with
      Chronic Pelvic Abdominal Pain and Appendicular Origin: Review of the Literature
      and Management.
AB  - The authors report a case of pseudomyxoma peritonei with gelatinous peritoneum in
      a 47-year-old-woman. The main symptom for discovery was a chronic pelvic
      abdominal pain. This disease is particularly rare. The gelatinous substance is
      often associated with a malignant ovarian tumor or appendicitis perforated.
      Currently, on the whole, an exploratory laparoscopy allows diagnosis, biopsies,
      and appendectomy. The treatment is essentially surgical. The prognosis depends on
      grade (1/3) and response to chemotherapy. This case was presented to the tumor
      board.

PMID- 29326942
TI  - The Development and Public Health Implications of Food Preferences in Children.
AB  - Food preferences are a primary determinant of dietary intake and behaviors, and
      they persist from early childhood into later life. As such, establishing
      preferences for healthy foods from a young age is a promising approach to
      improving diet quality, a leading contributor to cardiometabolic health. This
      narrative review first describes the critical period for food preference
      development starting in utero and continuing through early childhood. Infants'
      innate aversion to sour and bitter tastes can lead them to initially reject some
      healthy foods such as vegetables. Infants can learn to like these foods through
      exposures to their flavors in utero and through breastmilk. As solid foods are
      introduced through toddlerhood, children's food preferences are shaped by parent
      feeding practices and environmental factors such as food advertising. Next, we
      discuss two key focus areas to improve diet quality highlighted by the current
      understanding of food preferences: (1) promoting healthy food preferences through
      breastfeeding and early exposures to healthy foods and (2) limiting the extent to
      which innate preferences for sweet and salty tastes lead to poor diet quality. We
      use an ecological framework to summarize potential points of intervention and
      provide recommendations for these focus areas, such as worksite benefits that
      promote breastfeeding, and changes in food retail and service environments.
      Individuals' choices around breastfeeding and diet may ultimately be influenced
      by policy and community-level factors. It is thus crucial to take a multilevel
      approach to establish healthy food preferences from a young age, which have the
      potential to translate into lifelong healthy diet.

PMID- 29326944
TI  - AB0/Rhesus Blood Group Does Not Influence Clinicopathological Tumor
      Characteristics or Oncological Outcome in Patients Undergoing Radical
      Prostatectomy.
AB  - Objectives: AB0 blood group is an inherited characteristic that has been
      associated with the incidence as well as the prognosis of several malignancies.
      The aim of the current study was to clarify the role of the blood group in cancer
      epidemiology and clinical outcome of patients with prostate cancer (PCa).
      Methods: Data from 3,574 patients undergoing radical prostatectomy between 2009
      and 2010 at a single European institution were retrospectively analyzed. The
      correlation of AB0 and Rhesus blood group with PCa-related characteristics and
      oncological outcome were evaluated using univariable and multivariable Cox
      proportional hazard models. Results: Median follow-up was 36.9 months. The
      overall distributions of AB0, as well as Rhesus blood groups among patients with
      PCa, did not differ from the distribution observed in the normal population.
      There was no significant association between AB0/Rhesus blood groups and Gleason
      score, prostate volume, surgical margin, pT-stage, pN-status, or preoperative
      prostate-specific antigen level. In multivariable Cox regression analysis, no
      statistically significant correlation between AB0/Rhesus group and biochemical
      recurrence was observed (all p > 0.05). Conclusion: Our data suggest no relevant
      association of AB0/Rhesus blood group with adverse clinicopathological tumor
      characteristics or oncological outcome after surgery in contrast to several other
      malignancies.

PMID- 29326945
TI  - Biochemical Properties of Human D-Amino Acid Oxidase.
AB  - D-amino acid oxidase catalyzes the oxidative deamination of D-amino acids. In the
      brain, the NMDA receptor coagonist D-serine has been proposed as its
      physiological substrate. In order to shed light on the mechanisms regulating D
      serine concentration at the cellular level, we biochemically characterized human
      DAAO (hDAAO) in greater depth. In addition to clarify the physical-chemical
      properties of the enzyme, we demonstrated that divalent ions and nucleotides do
      not affect flavoenzyme function. Moreover, the definition of hDAAO substrate
      specificity demonstrated that D-cysteine is the best substrate, which made it
      possible to propose it as a putative physiological substrate in selected tissues.
      Indeed, the flavoenzyme shows a preference for hydrophobic amino acids, some of
      which are molecules relevant in neurotransmission, i.e., D-kynurenine, D-DOPA,
      and D-tryptophan. hDAAO shows a very low affinity for the flavin cofactor. The
      apoprotein form exists in solution in equilibrium between two alternative
      conformations: the one at higher affinity for FAD is favored in the presence of
      an active site ligand. This may represent a mechanism to finely modulate hDAAO
      activity by substrate/inhibitor presence. Taken together, the peculiar properties
      of hDAAO seem to have evolved in order to use this flavoenzyme in different
      tissues to meet different physiological needs related to D-amino acids.

PMID- 29326947
TI  - Echocardiographic Image Quality Deteriorates with Age in Children and Young
      Adults with Duchenne Muscular Dystrophy.
AB  - Background: Advances in medical care for patients with Duchenne muscular
      dystrophy (DMD) have resulted in improved survival and an increased prevalence of
      cardiomyopathy. Serial echocardiographic surveillance is recommended to detect
      early cardiac dysfunction and initiate medical therapy. Clinical anecdote
      suggests that echocardiographic quality diminishes over time, impeding accurate
      assessment of left ventricular systolic function. Furthermore, evidence-based
      guidelines for the use of cardiac imaging in DMD, including cardiac magnetic
      resonance imaging (CMR), are limited. The objective of our single-center,
      retrospective study was to quantify the deterioration in echocardiographic image
      quality with increasing patient age and identify an age at which CMR should be
      considered. Methods: We retrospectively reviewed and graded the image quality of
      serial echocardiograms obtained in young patients with DMD. The quality of 16
      left ventricular segments in two echocardiographic views was visually graded
      using a binary scoring system. An endocardial border delineation percentage
      (EBDP) score was calculated by dividing the number of segments with adequate
      endocardial delineation in each imaging window by the total number of segments
      present in that window and multiplying by 100. Linear regression analysis was
      performed to model the relationship between the EBDP scores and patient age.
      Results: Fifty-five echocardiograms from 13 patients (mean age 11.6 years, range
      3.6-19.9) were systematically reviewed. By 13 years of age, 50% of the
      echocardiograms were classified as suboptimal with >=30% of segments inadequately
      visualized, and by 15 years of age, 78% of studies were suboptimal. Linear
      regression analysis revealed a negative correlation between patient age and EBDP
      score (r = -2.49, 95% confidence intervals -4.73, -0.25; p = 0.032), with the
      score decreasing by 2.5% for each 1 year increase in age. Conclusion:
      Echocardiographic image quality declines with increasing age in DMD. Alternate
      imaging modalities may play a role in cases of poor echocardiographic image
      quality.

PMID- 29326948
TI  - Outer Membrane Protein 25 of Brucella Activates Mitogen-Activated Protein Kinase
      Signal Pathway in Human Trophoblast Cells.
AB  - Outer membrane protein 25 (OMP25), a virulence factor from Brucella, plays an
      important role in maintaining the structural stability of Brucella. Mitogen
      activated protein kinase (MAPK) signal pathway widely exists in eukaryotic cells.
      In this study, human trophoblast cell line HPT-8 and BALB/c mice were infected
      with Brucella abortus 2308 strain (S2308) and 2308DeltaOmp25 mutant strain. The
      expression of cytokines and activation of MAPK signal pathway were detected. We
      found that the expressions of tumor necrosis factor-alpha, interleukin-1, and
      interleukin-10 (IL-10) were increased in HPT-8 cells infected with S2308 and
      2308DeltaOmp25 mutant. S2308 also activated p38 phosphorylation protein,
      extracellular-regulated protein kinases (ERK), and Jun-N-terminal kinase (JNK)
      from MAPK signal pathway. 2308DeltaOmp25 could not activate p38, ERK, and JNK
      branches. Immunohistochemistry experiments showed that S2308 was able to activate
      phosphorylation of p38 and ERK in BABL/c mice. However, 2308DeltaOmp25 could
      weakly activate phosphorylation of p38 and ERK. These results suggest that Omp25
      played an important role in the process of Brucella activation of the MAPK signal
      pathway.

PMID- 29326949
TI  - Molecular Characterization and Cluster Analysis of Field Isolates of Avian
      Infectious Laryngotracheitis Virus from Argentina.
AB  - Avian infectious laryngotracheitis (ILT) is a worldwide infectious disease that
      causes important economic losses in the poultry industry. Although it is known
      that ILT virus (ILTV) is present in Argentina, there is no information about the
      circulating strains. With the aim to characterize them, seven different genomic
      regions (thymidine kinase, glycoproteins D, G, B, C, and J, and infected cell
      polypeptide 4) were partially sequenced and compared between field samples. The
      gJ sequence resulted to be the most informative segment, it allowed the
      differentiation among field sample strains, and also, between wild and vaccine
      viruses. Specific changes in selected nucleotidic positions led to the definition
      of five distinct haplotypes. Tests for detection of clustering were run to test
      the null hypothesis that ILTV haplotypes were randomly distributed in time in
      Argentina and in space in the most densely populated poultry region of this
      country, Entre Rios. From this study, it was possible to identify a 46 km radius
      cluster in which higher proportions of haplotypes 4 and 5 were observed, next to
      a provincial route in Entre Rios and a significant decline of haplotype 5 between
      2009 and 2011. Results here provide an update on the molecular epidemiology of
      ILT in Argentina, including data on specific genome segments that may be used for
      rapid characterization of the virus in the field. Ultimately, results will
      contribute to the surveillance of ILT in the country.

PMID- 29326950
TI  - Microtus arvalis and Arvicola scherman: Key Players in the Echinococcus
      multilocularis Life Cycle.
AB  - A broad range of rodent species are described as potential intermediate hosts for
      Echinococcus multilocularis, a wide-spread zoonotic cestode causing alveolar
      echinococcosis. However, little is known about the relative contribution of these
      species for parasite reproduction and the maintenance of its life cycle. In a
      comparative study in a high endemic region in Zurich, Switzerland, we
      investigated prevalence rates and fertility of E. multilocularis in the most
      abundant vole species as well as the predation rate of foxes on these species. To
      ensure that the fox families had access to different vole species and that these
      voles were exposed to the same environmental contamination with parasite eggs, we
      selected eight study plots where at least two rodent species co-occurred. The
      parasite prevalence in Microtus arvalis [11.0%, confidence intervals (CI) 8.9
      13.4] was significantly higher than in Arvicola scherman (5.3%, 3.9-7.1) and
      Myodes glareolus (3.9%, 2.0-6.7). None of the, only 29 individuals of, Microtus
      agrestis was infected (0%, 0.0-9.8) and the species was excluded for further
      analyses. Logistic regression models for the prevalences revealed significant
      differences between nearby study plots and higher infection rates for females,
      heavier individuals, and individuals trapped during spring, when the prevalence
      in M. arvalis peaked up to 65% (CI 50-79) in one plot. Furthermore, we detected
      significantly higher percentages of fertile infections in M. arvalis and M.
      glareolus than in A. scherman (OR 11.2 and 6.4, respectively) and a significantly
      higher protoscolex number in M. glareolus (median 100,000) than in M. arvalis
      (13,500) and A. scherman (4,290). The most abundant fox prey remains were of the
      genera Microtus (12.3%, CI 8.4-17.2) and Arvicola (11.5%, 7.7-16.3), whereas
      Myodes was never recorded as prey (0.0-1.3%). We conclude that M. arvalis and to
      a lesser extent A. scherman can be regarded as key intermediate hosts in Western
      and Central European high-endemic regions whereas M. glareolus and M. agrestis
      play a marginal role. We, therefore, postulate that distribution models of these
      species could contribute to predict parasite occurrence on a more detailed
      spatial scale than models of the distribution of foxes which have a very broad
      and uniform distribution.

PMID- 29326952
TI  - Recent Advances in Radiotracer Imaging Hold Potential for Future Refined
      Evaluation of Epilepsy in Veterinary Neurology.
AB  - Non-invasive nuclear imaging by positron emission tomography and single photon
      emission computed tomography has significantly contributed to epileptic focus
      localization in human neurology for several decades now. Offering functional
      insight into brain alterations, it is also of particular relevance for epilepsy
      research. Access to these techniques for veterinary medicine is becoming more and
      more relevant and has already resulted in first studies in canine patients. In
      view of the substantial proportion of drug-refractory epileptic dogs and cats,
      image-guided epileptic focus localization will be a prerequisite for selection of
      patients for surgical focus resection. Moreover, radiotracer imaging holds
      potential for a better understanding of the pathophysiology of underlying
      epilepsy syndromes as well as to forecast disease risk after epileptogenic brain
      insults. Importantly, recent advances in epilepsy research demonstrate the
      suitability and value of several novel radiotracers for non-invasive assessment
      of neuroinflammation, blood-brain barrier alterations, and neurotransmitter
      systems. It is desirable that veterinary epilepsy patients will also benefit from
      these promising developments in the medium term. This paper reviews the current
      use of radiotracer imaging in the veterinary epilepsy patient and suggests
      possible future directions for the technique.

PMID- 29326953
TI  - Hyperintensity of Cerebrospinal Fluid on T2-Weighted Fluid-Attenuated Inversion
      Recovery Magnetic Resonance Imaging Caused by High Inspired Oxygen Fraction.
AB  - In veterinary medicine, patients undergo magnetic resonance imaging (MRI) under
      general anesthesia to enable acquisition of artifact-free images. The fraction of
      inspired oxygen (FiO2) ranges between 30 and 95%. In humans, a high FiO2 is
      associated with incomplete signal suppression of peripheral cerebrospinal fluid
      (CSF) spaces on T2-weighted fluid-attenuated inversion recovery (T2w-FLAIR)
      sequences. The influence of FiO2 on T2w-FLAIR images remains unreported in small
      animals. The aim of this prospective study was to investigate whether a high FiO2
      is associated with hyperintensity in peripheral CSF spaces on T2w-FLAIR images in
      dogs and cats. Client-owned patients undergoing brain MRI were prospectively
      enrolled. Animals with brain parenchymal abnormalities and/or meningeal contrast
      enhancement on MRI images and/or abnormal CSF analysis were excluded.
      Consequently, twelve patients were enrolled. Anesthesia was maintained by
      isoflurane 0.5-1 minimal alveolar concentration in 30% oxygen. After acquisition
      of transverse and dorsal T2w-FLAIR images, the FiO2 was increased to 95%. The T2w
      FLAIR sequences were then repeated after 40 min. Arterial blood gas analysis was
      performed in six patients at the same time as T2w-FLAIR sequence acquisition.
      Plot profiles of the signal intensity (SI) from CSF spaces of three cerebral
      sulci and adjacent gray and white matter were generated. SI ratios of CSF space
      and white matter were compared between the T2w-FLAIR images with 30 and 95% FiO2.
      An observer blinded to the FiO2, subjectively evaluated the SI of peripheral CSF
      spaces on T2w-FLAIR images as high or low. There was significant difference in
      the partial pressure of oxygen between the two arterial samples (P < 0.001). The
      SI ratios obtained from the T2w-FLAIR images with 95% FiO2 were significantly
      higher compared with those obtained from the T2w-FLAIR images with 30% FiO2 (P <
      0.05). The peripheral CSF spaces were subjectively considered hyperintense in 11
      of 12 cases on T2w-FLAIR images with 95% FiO2 (P < 0.005). A clear difference in
      SI, dependent on the FiO2 was seen in the peripheral CSF spaces on T2w-FLAIR
      images. In conclusion, the influence of FiO2 must be considered when
      differentiating pathological and normal CSF spaces on T2w-FLAIR images in dogs
      and cats.

PMID- 29326951
TI  - Identification of Atypical Enteropathogenic Escherichia coli O98 from Golden Snub
      Nosed Monkeys with Diarrhea in China.
AB  - Fecal samples (n = 76) were collected from 38 snub-nosed monkeys (Rhinopithecus
      roxellana) in Shennongjia National Nature Reserve (China) and examined for the
      presence of enteropathogenic Escherichia coli (EPEC). The 56 samples originated
      from 30 free-ranging monkeys on the reserve and 20 samples from 8 captive monkeys
      that were previously rescued and kept at the research center. Eight diarrhea
      samples were collected from four of the eight captive monkeys (two samples from
      each monkey), and two EPEC strains (2.6%) (95% confidence interval 0.3-9.2%) were
      isolated from two fecal samples from two diarrheic monkeys. Both strains belonged
      to serotype O98 and phylogenetic group D (TspE4C2+, ChuA+). The virulence gene
      detection identified these strains as an atypical EPEC (aEPEC) (bfpB - , stx1 - ,
      and stx2-) with the subtype eae+, escV+, and intiminbeta+. These strains were
      highly sensitive to all the antibiotics tested. The lethal dose 50% of the two
      isolates in Kunming mice was 7.40 * 108 CFU/0.2 mL and 2.40 * 108 CFU/0.2 mL,
      respectively, indicating low virulence. Based on the report that this serotype
      had been isolated from some other non-human animals and humans with diarrhea, the
      first identification of aEPEC O98 strains and their drug resistance profile in R.
      roxellana is of ecological significance for disease control in this endangered
      species.

PMID- 29326954
TI  - Endoparasites of Wild Mammals Sheltered in Wildlife Hospitals and Rehabilitation
      Centres in Greece.
AB  - Wildlife parasitic diseases represent an important field of investigation as they
      may have a significant impact on wild animals' health and fitness, and may also
      have zoonotic implications. This study aimed to investigate the occurrence of
      endoparasites in wild mammals admitted to wildlife hospitals and rehabilitation
      centres in Greece. Sixty-five animals belonging to 17 species and originated from
      various areas of continental and insular Greece were included in the survey. The
      most numerous animal species examined were hedgehogs (n = 19), red foxes (n =
      16), and European roe deer (n = 6). Faecal samples were collected individually
      and examined by floatation and sedimentation method. Parasites were found in 46
      (70.7%) of the animals. Most parasites found in canids, felids, and ruminants are
      of great relevance to the domestic animals' health and some of them are also of
      zoonotic importance. To the best of the author's knowledge, this is the first
      report of endoparasites in hedgehogs, roe deers, fallow deers, badgers, and bats,
      and the first report of the pulmonary nematode Troglostrongylus brevior in a wild
      cat in Greece. The significance of the parasites found in each animal species in
      regard to their health and their relevance to domestic animals and human health
      is discussed.

PMID- 29326946
TI  - Microvesicles in Atherosclerosis and Angiogenesis: From Bench to Bedside and
      Reverse.
AB  - Atherosclerosis (AT) is a progressive chronic disease involving lipid
      accumulation, fibrosis, and inflammation in medium and large-sized arteries, and
      it is the main cause of cardiovascular disease (CVD). AT is caused by
      dyslipidemia and mediated by both innate and adaptive immune responses. Despite
      lipid-lowering drugs have shown to decrease the risk of cardiovascular events
      (CVEs), there is a significant burden of AT-related morbidity and mortality.
      Identification of subjects at increased risk for CVE as well as discovery of
      novel therapeutic targets for improved treatment strategies are still unmet
      clinical needs in CVD. Microvesicles (MVs), small extracellular plasma membrane
      particles shed by activated and apoptotic cells have been widely linked to the
      development of CVD. MVs from vascular and resident cells by facilitating exchange
      of biological information between neighboring cells serve as cellular effectors
      in the bloodstream and play a key role in all stages of disease progression. This
      article reviews the current knowledge on the role of MVs in AT and CVD. Attention
      is focused on novel aspects of MV-mediated regulatory mechanisms from endothelial
      dysfunction, vascular wall inflammation, oxidative stress, and apoptosis to
      coagulation and thrombosis in the progression and development of
      atherothrombosis. MV contribution to vascular remodeling is also discussed, with
      a particular emphasis on the effect of MVs on the crosstalk between endothelial
      cells and smooth muscle cells, and their role regulating the active process of AT
      driven angiogenesis and neovascularization. This review also highlights the
      latest findings and main challenges on the potential prognostic, diagnostic, and
      therapeutic value of cell-derived MVs in CVD. In summary, MVs have emerged as new
      regulators of biological functions in atherothrombosis and might be instrumental
      in cardiovascular precision medicine; however, significant efforts are still
      needed to translate into clinics the latest findings on MV regulation and
      function.

PMID- 29326955
TI  - Welfare Consequences of Omitting Beak Trimming in Barn Layers.
AB  - Beak trimming is used worldwide as a method of reducing the damage to feathers
      and skin caused by injurious pecking in laying hens. However, beak trimming also
      causes some welfare issues as trimming the beak results in pain and sensory loss.
      Due to this dilemma, there is an ongoing discussion in several European countries
      about whether to ban beak trimming. In this study, we investigated the welfare
      consequences of keeping layers with intact beaks and examined for links between
      injurious pecking damage and keel bone damage on an individual level. A study was
      conducted on 10 commercial farms housing laying hens in the barn system. Each
      farm participated with a flock of beak-trimmed hens (T) and a flock of non
      trimmed (NT) hens that were visited around 32 and 62 weeks of age. During visits,
      the condition of plumage, skin, feet, and keel bone of 100 hens was assessed.
      Mortality was recorded by the producers. NT flocks had a lower prevalence of hens
      with good plumage condition around 32 weeks of age (94.1 vs. 99.6%, P < 0.001)
      and a higher prevalence of hens with poor plumage condition at 62 weeks of age
      (63.6 vs. 15.2%, P < 0.001) compared with T flocks. The prevalence of hens with
      keel bone deviations, with both keel bone fractures and deviations and with body
      wounds, was higher in NT flocks compared with T flocks at both ages (P < 0.001).
      Accumulated mortality from placement to end of production tended to be higher in
      NT flocks compared with T flocks (14.2 vs. 8.6%; P = 0.06). The prevalence of
      keel bone damage was higher among hens with poor plumage condition than hens with
      moderate/good plumage condition (31.5 vs. 22.2%; P < 0.001). Thus, omitting beak
      trimming had negative consequences for the condition of plumage, skin, and keel
      bone, and tended to increase mortality, highlighting the risk of reduced welfare
      when keeping layers with intact beaks. In addition, injurious pecking damage was
      found to be positively linked to keel bone damage. The causal relation is
      unknown, but we propose that fearfulness is an important factor.

PMID- 29326956
TI  - MLVA and LPS Characteristics of Brucella canis Isolated from Humans and Dogs in
      Zhejiang, China.
AB  - Background: Brucella canis is a pathogenic bacterium that causes brucellosis in
      dogs, and its zoonotic potential has been increasing in recent years. B. canis is
      a rare source of human brucellosis in China, where Brucella melitensis has been
      the major pathogen associated with human brucellosis outbreaks. In late 2011, a
      case of a B. canis infection was detected in a human patient in Zhejiang
      Province, China. To compare the genotypes between strains of B. canis isolated
      from the patient and from dogs, a multiple-locus variable-number tandem-repeat
      analysis (MLVA-16) was performed. In addition, the lipopolysaccharide-synthesis
      related genes were analyzed with the B. canis reference strain RM6/66. Results:
      32 B. canis strains were divided into 26 genotypes using MLVA-16 [Hunter-Gaston
      Diversity Index (HGDI) = 0.976]. The HGDI indexes for various loci ranged between
      0.000 and 0.865. All four Hangzhou isolates were indistinguishable using panel 1
      (genotype 3) and panel 2A (genotype 28). However, these strains were distinctly
      different from other isolates from Beijing, Jiangsu, Liaoning, and Inner Mongolia
      at Bruce 09. The emergence of a human B. canis infection was limited to an area.
      Comparative analysis indicated B. canis from canines and humans have no
      differences in lipopolysaccharide-synthesis locus. Conclusion: The comprehensive
      approaches have been used to analyze human and canine B. canis isolates,
      including molecular epidemiological and LPS genetic characteristics. Further
      detailed analysis of the whole genomic sequencing will contribute to
      understanding of the pathogenicity of B. canis in humans.

PMID- 29326958
TI  - Performance and Return to Sport After Thumb Ulnar Collateral Ligament Repair in
      Major League Baseball Players.
AB  - Background: Acute ruptures of the ulnar collateral ligament (UCL) of the thumb
      are common injuries in sports. Surgical repair has yielded excellent results and
      high return-to-sport (RTS) rates in elite athletes. Purpose: To determine (1) the
      RTS rate in Major League Baseball (MLB) players following thumb UCL repair, (2)
      postoperative career length and games played per season, (3) pre- and
      postoperative performance, (4) postoperative performance compared with matched
      control players, and (5) whether dominant and nondominant hand injuries respond
      differently. Study Design: Cohort study; Level of evidence, 3. Methods: MLB
      players who underwent thumb UCL surgery from August 3, 1987, to September 6,
      2016, were identified. Demographic and performance data were collected for each
      player, and matched controls were identified. RTS in the MLB was defined as
      playing in at least 1 MLB game after surgery. Comparisons were made by use of
      paired-samples Student t tests. Results: Twenty-one players were identified, with
      a mean +/- SD age of 31.7 +/- 3.9 years and mean experience in the MLB of 8.6 +/-
      3.3 years at time of surgery. Twenty-one players (100%) achieved RTS in the MLB
      at a mean 120.0 +/- 75.9 days. No significant decrease was found in games per
      season or career length for any position following surgery. Infielders had a
      significantly lower rate of postoperative wins above replacement (WAR) compared
      with preoperatively (P = .006), but no significant differences in postoperative
      performance score were found compared with controls after the index date. No
      significant difference was found for performance between players undergoing
      surgery on their dominant hand and those who had surgery on their nondominant
      (glove) hand compared with controls. Conclusion: In this study, 100% of MLB
      players achieved RTS after thumb UCL repair, with in-season players returning at
      a mean of 8 weeks. Players who underwent thumb UCL repair played in a similar
      number of games per season and had similar career lengths in the MLB as controls.
      Infielders had a significantly lower postoperative WAR compared with
      preoperatively, but no significant postoperative performance score differences
      were noted when infielders were compared with post-index date matched controls.
      No significant performance differences were noted with regard to surgery on
      dominant and nondominant hands.

PMID- 29326957
TI  - Characterization of the Phospholipid Platelet-Activating Factor As a Mediator of
      Inflammation in Chickens.
AB  - Lipid mediators are known to play important roles in the onset and resolution
      phases of the inflammatory response in mammals. The phospholipid platelet
      activating factor (PAF) is a pro-inflammatory lipid mediator which participates
      in vascular- and innate immunity-associated processes by increasing vascular
      permeability, by facilitating leukocyte adhesion to the endothelium, and by
      contributing to phagocyte activation. PAF exerts its function upon binding to its
      specific receptor, PAF receptor (PAFR), which is abundantly expressed in
      leukocytes and endothelial cells (ECs). In chickens, lipid mediators and their
      functions are still poorly characterized, and the role of PAF as an inflammatory
      mediator has not yet been investigated. In the present study we demonstrate that
      primary chicken macrophages express PAFR and lysophosphatidylcholine
      acyltransferase 2 (LPCAT2), the latter being essential to PAF biosynthesis during
      inflammation. Also, exogenous PAF treatment induces intracellular calcium
      increase, reactive oxygen species release, and increased phagocytosis by primary
      chicken macrophages in a PAFR-dependent manner. We also show that PAF contributes
      to the Escherichia coli lipopolysaccharide (LPS)-induced pro-inflammatory
      response and boosts the macrophage response to E. coli LPS via
      phosphatidylinositol 3-kinase/Akt- and calmodulin kinase II-mediated
      intracellular signaling pathways. Exogenous PAF treatment also increases avian
      pathogenic E. coli intracellular killing by chicken macrophages, and PAFR and
      LPCAT2 are upregulated in chicken lungs and liver during experimental pulmonary
      colibacillosis. Finally, exogenous PAF treatment increases cell permeability and
      upregulates the expression of genes coding for proteins involved in leukocyte
      adhesion to the endothelium in primary chicken endothelial cells (chAEC). In
      addition to these vascular phenomena, PAF boosts the chAEC inflammatory response
      to bacteria-associated molecular patterns in a PAFR-dependent manner. In
      conclusion, we identified PAF as an inflammation amplifier in chicken macrophages
      and ECs, which suggests that PAF could play important roles in the endothelium
      innate immunity interface in birds during major bacterial infectious diseases
      such as colibacillosis.

PMID- 29326959
TI  - Use of Antibiotic Prophylaxis for Tooth Extractions, Dental Implants, and
      Periodontal Surgical Procedures.
AB  - Background: Guidelines for antibiotics prior to dental procedures for patients
      with specific cardiac conditions and prosthetic joints have changed, reducing
      indications for antibiotic prophylaxis. In addition to guidelines focused on
      patient comorbidities, systematic reviews specific to dental extractions and
      implants support preprocedure antibiotics for all patients. However, data on
      dentist adherence to these recommendations are scarce. Methods: This was a cross
      sectional study of veterans undergoing tooth extractions, dental implants, and
      periodontal procedures. Patients receiving antibiotics for oral or nonoral
      infections were excluded. Data were collected through manual review of the health
      record. Results: Of 183 veterans (mean age, 62 years; 94.5% male) undergoing the
      included procedures, 82.5% received antibiotic prophylaxis (mean duration, 7.1 +/
      1.6 days). Amoxicillin (71.3% of antibiotics) and clindamycin (23.8%) were
      prescribed most frequently; 44.7% of patients prescribed clindamycin were not
      labeled as penicillin allergic. Of those who received prophylaxis, 92.1% received
      postprocedure antibiotics only, 2.6% received preprocedural antibiotics only, and
      5.3% received pre- and postprocedure antibiotics. When prophylaxis was indicated,
      87.3% of patients received an antibiotic. However, 84.9% received postprocedure
      antibiotics when preprocedure administration was indicated. While the majority of
      antibiotics were indicated, only 8.2% of patients received antibiotics
      appropriately. The primary reason was secondary to prolonged duration. Three
      months postprocedure, there were no occurrences of Clostridium difficile
      infection, infective endocarditis, prosthetic joint infections, or postprocedure
      oral infections. Conclusion: The majority of patients undergoing a dental
      procedure received antibiotic prophylaxis as indicated. Although patients for
      whom antibiotic prophylaxis was indicated should have received a single
      preprocedure dose, most antibiotics were prescribed postprocedure. Dental
      stewardship efforts should ensure appropriate antibiotic timing, indication, and
      duration.

PMID- 29326960
TI  - Risk Factors for Clinician-Diagnosed Lyme Arthritis, Facial Palsy, Carditis, and
      Meningitis in Patients From High-Incidence States.
AB  - Background: Clinical features of Lyme disease (LD) range from localized skin
      lesions to serious disseminated disease. Information on risk factors for Lyme
      arthritis, facial palsy, carditis, and meningitis is limited but could facilitate
      disease recognition and elucidate pathophysiology. Methods: Patients from high
      incidence states treated for LD during 2005-2014 were identified in a nationwide
      insurance claims database using the International Classification of Diseases,
      Ninth Revision code for LD (088.81), antibiotic treatment history, and clinically
      compatible codiagnosis codes for LD manifestations. Results: Among 88022 unique
      patients diagnosed with LD, 5122 (5.8%) patients with 5333 codiagnoses were
      identified: 2440 (2.8%) arthritis, 1853 (2.1%) facial palsy, 534 (0.6%) carditis,
      and 506 (0.6%) meningitis. Patients with disseminated LD had lower median age (35
      vs 42 years) and higher male proportion (61% vs 50%) than nondisseminated LD.
      Greatest differential risks included arthritis in males aged 10-14 years (odds
      ratio [OR], 3.5; 95% confidence interval [CI], 3.0-4.2), facial palsy (OR, 2.1;
      95% CI, 1.6-2.7) and carditis (OR, 2.4; 95% CI, 1.6-3.6) in males aged 20-24
      years, and meningitis in females aged 10-14 years (OR, 3.4; 95% CI, 2.1-5.5)
      compared to the 55-59 year referent age group. Males aged 15-29 years had the
      highest risk for complete heart block, a potentially fatal condition.
      Conclusions: The risk and manifestations of disseminated LD vary by age and sex.
      Provider education regarding at-risk populations and additional investigations
      into pathophysiology could enhance early case recognition and improve patient
      management.

PMID- 29326961
TI  - Trends in suicidality among sexual minority and heterosexual students in a
      Canadian population-based cohort study.
AB  - Objectives: Despite evidence from numerous studies that document disparities in
      suicidality for sexual minorities, few have investigated whether or not these
      trends have improved over time, which is the objective of the current study.
      Methods: Using school-based population data over a 15-year period (1998 to 2013),
      multivariate logistic regressions were used to calculate age-adjusted odds ratios
      separately by gender. Interactions were included to test widening or narrowing
      disparities within orientation groups, which makes this one of the first studies
      to test whether gaps in disparities between heterosexual and sexual minorities
      have widened or narrowed over time. Results: Results show that sexual minority
      youth are persistently at a greater risk for suicidal behaviour, a trend that has
      continued particularly for bisexual youth of both sexes. Results also suggest
      that the gap in suicidal behaviour is widening among some female sexual
      orientation groups, yet narrowing for other male sexual orientation groups.
      Conclusions: These findings have important public health implications, especially
      since we see decreases in suicidal behaviour for heterosexual adolescents, but
      not in the same way for many sexual minority youth, despite advances in social
      acceptance of gay, lesbian, and bisexual issues in North America.

PMID- 29326963
TI  - Mutant Huntingtin Secretion in Neuro2A Cells and Rat Primary Cortical Neurons.
AB  - Quantitative analysis of proteins secreted from the cells poses a challenge due
      to their low abundance and the interfering presence of a large amount of bovine
      serum albumin (BSA) in the cell culture media. We established assays for
      detection of mutant huntingtin (mHtt) secreted from Neuro2A cell line stably
      expressing mHtt and rat primary cortical neurons by Western blotting. Our
      protocol is based on reducing the amounts of BSA in the media while maintaining
      cell viability and secretory potential, and concentrating the media prior to
      analysis by means of ultrafiltration.

PMID- 29326965
TI  - Average crop yield (2001-2017) in Ethiopia: Trends at national, regional and
      zonal levels.
AB  - This article presents average agricultural yield data per hectare for key cereal,
      legume and root crops from 2001 until 2017. Data was obtained from the annual
      Agricultural Sample Surveys of the Central Statistics Agency (CSA) of Ethiopia.
      We present data at national, regional (SNNPRS) and zonal (Wolaita) levels. The
      data shows that average yields for all crops, at all levels, show increasing
      trends during the time period. Data for the main cereal crops is consistent and
      aligns with literature relatively well, however we raise questions about the root
      crop data in an effort to encourage greater critical reflection of components of
      data from the CSA.

PMID- 29326964
TI  - Transportation and Other Nonfinancial Barriers Among Uninsured Primary Care
      Patients.
AB  - Introduction: Nonfinancial barriers are frequent causes of unmet need in health
      care services. The significance of transportation barriers can weigh more than
      the issues of access to care. The purpose of this cross-sectional study was to
      examine transportation and other nonfinancial barriers among low-income uninsured
      patients of a safety net health-care facility (free clinic). Methods: The survey
      data were collected from patients aged 18 years and older who spoke English or
      Spanish at a free clinic, which served uninsured individuals in poverty in the
      United States. Results: Levels of transportation barriers were associated with
      levels of other nonfinancial barriers. Higher levels of nonfinancial barriers
      were associated with elevation in levels of stress and poorer self-rated general
      health. Higher educational attainment and employment were associated with an
      increase in other nonfinancial barriers. Conclusion: Focusing only on medical
      interventions might not be sufficient for the well-being of the underserved
      populations. Future studies should examine integrative care programs that include
      medical treatment and social services together and evaluate such programs to
      improve care for underserved populations.

PMID- 29326966
TI  - Transcriptome datasets of macrophages infected with different strains of
      Leptospira spp.
AB  - The datasets reported herein provide information about microarray experiment of
      macrophage cell line J774A.1 infected with three different strains of Leptospira
      spp. Transcriptomic profiles were generated using Affymetrix(r) Mouse Gene 2.1 ST
      Array Strip. Data was normalized and statically process, p-value < 0.01, FDR <
      0.05 and log2 fold change (+/- 2). The microarray raw data are available in Gene
      Expression Omnibus (GEO) under accession number GSE105141.

PMID- 29326967
TI  - HR-TEM and FT-Raman dataset of the caffeine interacted Phe-Phe peptide nanotube
      for possible sensing applications.
AB  - Sensing ability of caffeine interaction with Phe-Phe annotates (PNTs), is
      presented (Govindhan et al., 2017; Karthikeyan et al., 2014; Tavagnacco et al.,
      2013; Kennedy et al., 2011; Wang et al., 2017) [1-5] in this data set.
      Investigation of synthesized caffeine carrying peptide nanotubes are carried out
      by FT-Raman spectral analysis and high resolution transmission electron
      microscopy (HR-TEM). Particle size of the caffeine loaded PNTs is < 40 nm. The FT
      Raman spectrum signals are enhanced in the region of 400-1700 cm-1. These data
      are ideal tool for the applications like biosensing and drug delivery research
      (DDS).

PMID- 29326962
TI  - Emerging Issues in AAV-Mediated In Vivo Gene Therapy.
AB  - In recent years, the number of clinical trials in which adeno-associated virus
      (AAV) vectors have been used for in vivo gene transfer has steadily increased.
      The excellent safety profile, together with the high efficiency of transduction
      of a broad range of target tissues, has established AAV vectors as the platform
      of choice for in vivo gene therapy. Successful application of the AAV technology
      has also been achieved in the clinic for a variety of conditions, including
      coagulation disorders, inherited blindness, and neurodegenerative diseases, among
      others. Clinical translation of novel and effective "therapeutic products" is,
      however, a long process that involves several cycles of iterations from bench to
      bedside that are required to address issues encountered during drug development.
      For the AAV vector gene transfer technology, several hurdles have emerged in both
      preclinical studies and clinical trials; addressing these issues will allow in
      the future to expand the scope of AAV gene transfer as a therapeutic modality for
      a variety of human diseases. In this review, we will give an overview on the
      biology of AAV vector, discuss the design of AAV-based gene therapy strategies
      for in vivo applications, and present key achievements and emerging issues in the
      field. We will use the liver as a model target tissue for gene transfer based on
      the large amount of data available from preclinical and clinical studies.

PMID- 29326968
TI  - Data on wastewater treatment plant by using wetland method, Babol, Iran.
AB  - Date in this paper highlights the applications of constructed horizontal surface
      flow (HF-CW) wetland with two different local plants (Louis latifoila and
      Phragmites -australis (Cav.) Trin) at the wastewater treatment plant in Babol
      city. This system was designed as an advanced treatment unit in field scale after
      the treatment plant. Parameters such as Total Dissolved Solid (TDS), Total
      Suspended Solid (TSS), Turbidity, Biological Oxygen Demand (BOD) and Chemical
      Oxygen Demand (COD), were investigated. The result shows that treatment
      efficiency increases with the passage of time. The efficiency of Phragmites
      planted setups in open environment was fairly good for all studied parameters
      (28.6% of TDS, 94.4% for TSS, 79.8% for turbidity, 93.7% for BOD and 82.6% for
      COD). The efficiency of the latifoila set up was also good, but lower than that
      of Phragmites (26.5% of TDS, 76.9% for TSS, 71.5% for turbidity, 79.1 for BOD and
      68.8% for COD). In brief, the obtained dates show that using local plants in (HF
      CW) wetland not only effectively reduces various contaminants from the effluent
      of the wastewater according to Effluent Guideline regulations (WHO & EPA), but it
      is also a cost- effective and environmentally friendly method. Also, it was
      calculated that in full scale operation [time (1 day) and a depth (0.3 m)], 8 ha
      of wetland was needed.

PMID- 29326969
TI  - Data set of enzyme fingerprinting of dietary fibre components (arabinoxylan and
      beta-glucan) in old and modern Italian durum wheat genotypes.
AB  - The data presented are related to the research article entitled "Comparison of
      the dietary fibre composition of old and modern durum wheat (Triticum turgidum
      spp. durum) genotypes" (De Santis et al., 2018) [1]. This article provides
      details of the structures of the major dietary fibre components, arabinoxylan and
      beta-glucan, in semolina and wholemeal flour of old and modern Italian durum
      wheat genotypes grown in two seasons, determined by enzyme digestion followed by
      high-performance anion-exchange chromatography (enzyme fingerprinting).

PMID- 29326970
TI  - Revisiting sweat chloride test results based on recent guidelines for diagnosis
      of cystic fibrosis.
AB  - Objectives: Recent sweat chloride guidelines published by the Cystic Fibrosis
      Foundation changed the intermediate sweat chloride concentration range from 40-59
      mmol/L to 30-59 mmol/L for age > 6 months. We wanted to know how this new
      guideline would impact detection of cystic fibrosis among patients who previously
      had sweat tests done at Texas Children's Hospital. Methods: We revisited sweat
      chloride test results (n = 3012) in the last 5 years at Texas Children's Hospital
      based on the new guidelines on diagnosis of cystic fibrosis from the Cystic
      Fibrosis Foundation. Results: We identified 125 patients that would be
      reclassified in the intermediate sweat chloride value with the new guidelines
      that were classified as "unlikely to have CF" in the previous guidelines. 8 (32%)
      patients with CFTR gene testing were positive for CFTR gene mutation(s). 4 (50%)
      of these patients were identified to have 2 CFTR mutations. One had variant
      combination that was reported to cause CF but all were diagnosed with CFTR
      related metabolic syndrome. Conclusion: Our findings concur with the new CF
      diagnosis guidelines that changing the intermediate cut-off to 30-59 mmol/L sweat
      chloride concentration in combination with CFTR genetic analysis enhances the
      probability of identifying individuals that have risk of developing CF or have CF
      and enables for earlier therapeutic intervention.

PMID- 29326971
TI  - Cervical clear cell adenocarcinoma with an exceptionally low proliferation index:
      Report of a case.
AB  - *A histologically low-grade cervical clear cell lesion was
      observed.*Proliferating cells were seen only at the periphery of this lesion.*Due
      to its low proliferation index, this may represent a precursor of clear cell
      carcinoma.*Further definition of such lesions may allow for more minimal
      management.

PMID- 29326972
TI  - Aggressive neuroendocrine tumor of the ovary with multiple metastases treated
      with everolimus: A case report.
AB  - *Neuroendocrine tumors (NETs) frequently occur in the lungs or the
      gastrointestinal tract; they are uncommon in the ovary.*The mammalian target of
      rapamycin (mTOR) pathway has been reported as a treatment for advanced NETs.*We
      describe a patient with an aggressive primary ovarian NET, successfully treated
      with everolimus (an mTOR inhibitor).

PMID- 29326973
TI  - A rare case of endometrial cancer metastatic to the uveal choroid.
AB  - *Choroid metastases are extremely rare in endometrial cancer.*Choroid metastases
      can present as many different eye complaints.*Comprehensive eye exams are
      important in patients with visual complaints.

PMID- 29326974
TI  - The largest deep-ocean silicic volcanic eruption of the past century.
AB  - The 2012 submarine eruption of Havre volcano in the Kermadec arc, New Zealand, is
      the largest deep-ocean eruption in history and one of very few recorded submarine
      eruptions involving rhyolite magma. It was recognized from a gigantic 400-km2
      pumice raft seen in satellite imagery, but the complexity of this event was
      concealed beneath the sea surface. Mapping, observations, and sampling by
      submersibles have provided an exceptionally high fidelity record of the seafloor
      products, which included lava sourced from 14 vents at water depths of 900 to
      1220 m, and fragmental deposits including giant pumice clasts up to 9 m in
      diameter. Most (>75%) of the total erupted volume was partitioned into the pumice
      raft and transported far from the volcano. The geological record on submarine
      volcanic edifices in volcanic arcs does not faithfully archive eruption size or
      magma production.

PMID- 29326976
TI  - Ultrafast rotation of magnetically levitated macroscopic steel spheres.
AB  - Our world is increasingly powered by electricity, which is largely converted to
      or from mechanical energy using electric motors. Several applications have driven
      the miniaturization of these machines, resulting in high rotational speeds.
      Although speeds of several hundred thousand revolutions per minute have been used
      industrially, we report the realization of an electrical motor reaching 40
      million rpm to explore the underlying physical boundaries. Millimeter-scale steel
      spheres, which are levitated and accelerated by magnetic fields inside a vacuum,
      are used as a rotor. Circumferential speeds exceeding 1000 m/s and centrifugal
      accelerations of more than 4 * 108 times gravity were reached. The results open
      up new research possibilities, such as the testing of materials under extreme
      centrifugal load, and provide insights into the development of future electric
      drive systems.

PMID- 29326975
TI  - Identifying the substrate proteins of U-box E3s E4B and CHIP by orthogonal
      ubiquitin transfer.
AB  - E3 ubiquitin (UB) ligases E4B and carboxyl terminus of Hsc70-interacting protein
      (CHIP) use a common U-box motif to transfer UB from E1 and E2 enzymes to their
      substrate proteins and regulate diverse cellular processes. To profile their
      ubiquitination targets in the cell, we used phage display to engineer E2-E4B and
      E2-CHIP pairs that were free of cross-reactivity with the native UB transfer
      cascades. We then used the engineered E2-E3 pairs to construct "orthogonal UB
      transfer (OUT)" cascades so that a mutant UB (xUB) could be exclusively used by
      the engineered E4B or CHIP to label their substrate proteins. Purification of xUB
      conjugated proteins followed by proteomics analysis enabled the identification of
      hundreds of potential substrates of E4B and CHIP in human embryonic kidney 293
      cells. Kinase MAPK3 (mitogen-activated protein kinase 3), methyltransferase PRMT1
      (protein arginine N-methyltransferase 1), and phosphatase PPP3CA (protein
      phosphatase 3 catalytic subunit alpha) were identified as the shared substrates
      of the two E3s. Phosphatase PGAM5 (phosphoglycerate mutase 5) and deubiquitinase
      OTUB1 (ovarian tumor domain containing ubiquitin aldehyde binding protein 1) were
      confirmed as E4B substrates, and beta-catenin and CDK4 (cyclin-dependent kinase
      4) were confirmed as CHIP substrates. On the basis of the CHIP-CDK4 circuit
      identified by OUT, we revealed that CHIP signals CDK4 degradation in response to
      endoplasmic reticulum stress.

PMID- 29326977
TI  - Monitoring reservoir response to earthquakes and fluid extraction, Salton Sea
      geothermal field, California.
AB  - Continuous monitoring of in situ reservoir responses to stress transients
      provides insights into the evolution of geothermal reservoirs. By exploiting the
      stress dependence of seismic velocity changes, we investigate the temporal
      evolution of the reservoir stress state of the Salton Sea geothermal field
      (SSGF), California. We find that the SSGF experienced a number of sudden velocity
      reductions (~0.035 to 0.25%) that are most likely caused by openings of fractures
      due to dynamic stress transients (as small as 0.08 MPa and up to 0.45 MPa) from
      local and regional earthquakes. Depths of velocity changes are estimated to be
      about 0.5 to 1.5 km, similar to the depths of the injection and production wells.
      We derive an empirical in situ stress sensitivity of seismic velocity changes by
      relating velocity changes to dynamic stresses. We also observe systematic
      velocity reductions (0.04 to 0.05%) during earthquake swarms in mid-November 2009
      and late-December 2010. On the basis of volumetric static and dynamic stress
      changes, the expected velocity reductions from the largest earthquakes with
      magnitude ranging from 3 to 4 in these swarms are less than 0.02%, which suggests
      that these earthquakes are likely not responsible for the velocity changes
      observed during the swarms. Instead, we argue that velocity reductions may have
      been induced by poroelastic opening of fractures due to aseismic deformation. We
      also observe a long-term velocity increase (~0.04%/year) that is most likely due
      to poroelastic contraction caused by the geothermal production. Our observations
      demonstrate that seismic interferometry provides insights into in situ reservoir
      response to stress changes.

PMID- 29326978
TI  - Seismic signature of active intrusions in mountain chains.
AB  - Intrusions are a ubiquitous component of mountain chains and testify to the
      emplacement of magma at depth. Understanding the emplacement and growth
      mechanisms of intrusions, such as diapiric or dike-like ascent, is critical to
      constrain the evolution and structure of the crust. Petrological and geological
      data allow us to reconstruct magma pathways and long-term magma differentiation
      and assembly processes. However, our ability to detect and reconstruct the short
      term dynamics related to active intrusive episodes in mountain chains is
      embryonic, lacking recognized geophysical signals. We analyze an anomalously deep
      seismic sequence (maximum magnitude 5) characterized by low-frequency bursts of
      earthquakes that occurred in 2013 in the Apennine chain in Italy. We provide
      seismic evidences of fluid involvement in the earthquake nucleation process and
      identify a thermal anomaly in aquifers where CO2 of magmatic origin dissolves. We
      show that the intrusion of dike-like bodies in mountain chains may trigger
      earthquakes with magnitudes that may be relevant to seismic hazard assessment.
      These findings provide a new perspective on the emplacement mechanisms of
      intrusive bodies and the interpretation of the seismicity in mountain chains.

PMID- 29326980
TI  - Increased fluxes of shelf-derived materials to the central Arctic Ocean.
AB  - Rising temperatures in the Arctic Ocean region are responsible for changes such
      as reduced ice cover, permafrost thawing, and increased river discharge, which,
      together, alter nutrient and carbon cycles over the vast Arctic continental
      shelf. We show that the concentration of radium-228, sourced to seawater through
      sediment-water exchange processes, has increased substantially in surface waters
      of the central Arctic Ocean over the past decade. A mass balance model for 228Ra
      suggests that this increase is due to an intensification of shelf-derived
      material inputs to the central basin, a source that would also carry elevated
      concentrations of dissolved organic carbon and nutrients. Therefore, we suggest
      that significant changes in the nutrient, carbon, and trace metal balances of the
      Arctic Ocean are underway, with the potential to affect biological productivity
      and species assemblages in Arctic surface waters.

PMID- 29326979
TI  - Nanometer-precision linear sorting with synchronized optofluidic dual barriers.
AB  - The past two decades have witnessed the revolutionary development of optical
      trapping of nanoparticles, most of which deal with trapping stiffness larger than
      10-8 N/m. In this conventional regime, however, it remains a formidable challenge
      to sort out sub-50-nm nanoparticles with single-nanometer precision, isolating us
      from a rich flatland with advanced applications of micromanipulation. With an
      insightfully established roadmap of damping, the synchronization between optical
      force and flow drag force can be coordinated to attempt the loosely overdamped
      realm (stiffness, 10-10 to 10-8 N/m), which has been challenging. This paper
      intuitively demonstrates the remarkable functionality to sort out single gold
      nanoparticles with radii ranging from 30 to 50 nm, as well as 100- and 150-nm
      polystyrene nanoparticles, with single nanometer precision. The quasi-Bessel
      optical profile and the loosely overdamped potential wells in the microchannel
      enable those aforementioned nanoparticles to be separated, positioned, and
      microscopically oscillated. This work reveals an unprecedentedly meaningful
      damping scenario that enriches our fundamental understanding of particle kinetics
      in intriguing optical systems, and offers new opportunities for tumor targeting,
      intracellular imaging, and sorting small particles such as viruses and DNA.

PMID- 29326981
TI  - Adaptation required to preserve future high-end river flood risk at present
      levels.
AB  - Earth's surface temperature will continue to rise for another 20 to 30 years even
      with the strongest carbon emission reduction currently considered. The associated
      changes in rainfall patterns can result in an increased flood risk worldwide. We
      compute the required increase in flood protection to keep high-end fluvial flood
      risk at present levels. The analysis is carried out worldwide for subnational
      administrative units. Most of the United States, Central Europe, and Northeast
      and West Africa, as well as large parts of India and Indonesia, require the
      strongest adaptation effort. More than half of the United States needs to at
      least double their protection within the next two decades. Thus, the need for
      adaptation to increased river flood is a global problem affecting industrialized
      regions as much as developing countries.

PMID- 29326982
TI  - Discovery of slow magnetic fluctuations and critical slowing down in the
      pseudogap phase of YBa2Cu3O y.
AB  - The origin of the pseudogap region below a temperature T* is at the heart of the
      mysteries of cuprate high-temperature superconductors. Unusual properties of the
      pseudogap phase, such as broken time-reversal and inversion symmetry are observed
      in several symmetry-sensitive experiments: polarized neutron diffraction, optical
      birefringence, dichroic angle-resolved photoemission spectroscopy, second
      harmonic generation, and polar Kerr effect. These properties suggest that the
      pseudogap region is a genuine thermodynamic phase and are predicted by theories
      invoking ordered loop currents or other forms of intra-unit-cell (IUC) magnetic
      order. However, muon spin rotation (MUSR) and nuclear magnetic resonance (NMR)
      experiments do not see the static local fields expected for magnetic order,
      leaving room for skepticism. The magnetic resonance probes have much longer time
      scales, however, over which local fields could be averaged by fluctuations. The
      observable effect of the fluctuations in magnetic resonance is then dynamic
      relaxation. We have measured dynamic muon spin relaxation rates in single
      crystals of YBa2Cu3O y (6.72 < y < 6.95) and have discovered "slow" fluctuating
      magnetic fields with magnitudes and fluctuation rates of the expected orders of
      magnitude that set in consistently at temperatures Tmag ~ T*. The absence of any
      static field (to which MUSR would be linearly sensitive) is consistent with the
      finite correlation length from neutron diffraction. Equally important, these
      fluctuations exhibit the critical slowing down at Tmag expected near a time
      reversal symmetry breaking transition. Our results explain the absence of static
      magnetism and provide support for the existence of IUC magnetic order in the
      pseudogap phase.

PMID- 29326983
TI  - Detecting reciprocity at a global scale.
AB  - Reciprocity stabilizes cooperation from the level of microbes all the way up to
      humans interacting in small groups, but does reciprocity also underlie stable
      cooperation between larger human agglomerations, such as nation states? Famously,
      evolutionary models show that reciprocity could emerge as a widespread strategy
      for achieving international cooperation. However, existing studies have only
      detected reciprocity-driven cooperation in a small number of country pairs. We
      apply a new method for detecting mutual influence in dynamical systems to a new
      large-scale data set that records state interactions with high temporal
      resolution. Doing so, we detect reciprocity between many country pairs in the
      international system and find that these reciprocating country pairs exhibit
      qualitatively different cooperative dynamics when compared to nonreciprocating
      pairs. Consistent with evolutionary theories of cooperation, reciprocating
      country pairs exhibit higher levels of stable cooperation and are more likely to
      punish instances of noncooperation. However, countries in reciprocity-based
      relationships are also quicker to forgive single acts of noncooperation by
      eventually returning to previous levels of mutual cooperation. By contrast,
      nonreciprocating pairs are more likely to exploit each other's cooperation via
      higher rates of defection. Together, these findings provide the strongest
      evidence to date that reciprocity is a widespread mechanism for achieving
      international cooperation.

PMID- 29326984
TI  - Using parahydrogen to hyperpolarize amines, amides, carboxylic acids, alcohols,
      phosphates, and carbonates.
AB  - Hyperpolarization turns weak nuclear magnetic resonance (NMR) and magnetic
      resonance imaging (MRI) responses into strong signals, so normally impractical
      measurements are possible. We use parahydrogen to rapidly hyperpolarize
      appropriate 1H, 13C, 15N, and 31P responses of analytes (such as NH3) and
      important amines (such as phenylethylamine), amides (such as acetamide, urea, and
      methacrylamide), alcohols spanning methanol through octanol and glucose, the
      sodium salts of carboxylic acids (such as acetic acid and pyruvic acid), sodium
      phosphate, disodium adenosine 5'-triphosphate, and sodium hydrogen carbonate. The
      associated signal gains are used to demonstrate that it is possible to collect
      informative single-shot NMR spectra of these analytes in seconds at the micromole
      level in a 9.4-T observation field. To achieve these wide-ranging signal gains,
      we first use the signal amplification by reversible exchange (SABRE) process to
      hyperpolarize an amine or ammonia and then use their exchangeable NH protons to
      relay polarization into the analyte without changing its identity. We found that
      the 1H signal gains reach as high as 650-fold per proton, whereas for 13C, the
      corresponding signal gains achieved in a 1H-13C refocused insensitive nuclei
      enhanced by polarization transfer (INEPT) experiment exceed 570-fold and those in
      a direct-detected 13C measurement exceed 400-fold. Thirty-one examples are
      described to demonstrate the applicability of this technique.

PMID- 29326985
TI  - Use of an Autonomous Surface Vehicle reveals small-scale diel vertical migrations
      of zooplankton and susceptibility to light pollution under low solar irradiance.
AB  - Light is a major cue for nearly all life on Earth. However, most of our knowledge
      concerning the importance of light is based on organisms' response to light
      during daytime, including the dusk and dawn phase. When it is dark, light is most
      often considered as pollution, with increasing appreciation of its negative
      ecological effects. Using an Autonomous Surface Vehicle fitted with a
      hyperspectral irradiance sensor and an acoustic profiler, we detected and
      quantified the behavior of zooplankton in an unpolluted light environment in the
      high Arctic polar night and compared the results with that from a light-polluted
      environment close to our research vessels. First, in environments free of light
      pollution, the zooplankton community is intimately connected to the ambient light
      regime and performs synchronized diel vertical migrations in the upper 30 m
      despite the sun never rising above the horizon. Second, the vast majority of the
      pelagic community exhibits a strong light-escape response in the presence of
      artificial light, observed down to 100 m. We conclude that artificial light from
      traditional sampling platforms affects the zooplankton community to a degree
      where it is impossible to examine its abundance and natural rhythms within the
      upper 100 m. This study underscores the need to adjust sampling platforms,
      particularly in dim-light conditions, to capture relevant physical and biological
      data for ecological studies. It also highlights a previously unchartered
      susceptibility to light pollution in a region destined to see significant changes
      in light climate due to a reduced ice cover and an increased anthropogenic
      activity.

PMID- 29326988
TI  - Editorial.
AB  - Dear Colleagues, It is with pleasure that I hereby introduce the ninth issue of
      UIO. This issue covers a wide range of interesting topics. Some of the topics are
      also focus areas for the European Federation of Societies for Ultrasound in
      Medicine and Biology (EFSUMB), namely student education in ultrasound and
      elastography. Guidelines are available under www.efsumb.org.

PMID- 29326986
TI  - Measles virus: Background and oncolytic virotherapy.
AB  - Measles is a highly transmissible disease caused by measles virus and remains a
      major cause of child mortality in developing countries. Measles virus
      nucleoprotein (N) encapsidates the RNA genome of the virus for providing
      protection from host cell endonucleases and for specific recognition of viral RNA
      as template for transcription and replication. This protein is over-expressed at
      the time of viral replication. The C-terminal of N protein is intrinsically
      disordered, which enables this protein to interact with several host cell
      proteins. It was previously proved in our laboratory that N expressing human
      cancerous cells undergo programmed cell death because of reactive oxygen species
      (ROS) generation as well as Caspase 3 activation. The phosphoprotein (P) along
      with N protein enclosed viral genomic RNA forming a ribonucleoprotein complex
      (RNP). It also establishes interaction with the large protein (L) i.e. viral RNA
      dependent RNA polymerase to ensure viral replication within host cells. The host
      cell receptors of this virus are CD46, SLAM/CD150 and PVRL4. Measles virus is
      latently oncotropic in nature and possesses oncolytic property by syncytia
      formation. We try to highlight the application of this property in developing a
      virotherapeutic vehicle.

PMID- 29326987
TI  - Assessment of nutrient quality, heavy metals and phytotoxic properties of chicken
      manure on selected commercial vegetable crops.
AB  - Due to rapid expansion in the poultry industry, production of poultry manure has
      also consequently increased, resulting in unplanned disposal of this manure to
      the soil in some cases, with possible negative environmental consequences. In
      this study, 10 separate poultry manure samples were collected from different
      sites located in the central Eastern Cape, South Africa and characterized for
      chemical and phytotoxic properties. The poultry manures had an average neutral pH
      (range 6.94 - 7.97) whilst the electrical conductivity was highly variable from
      2.45 dS/m to 12.3 dS/m between the 10 sites. The high conductivity values
      recorded in some of the manures indicate that caution may need to be practiced
      when directly applying these manure to the soil, to avoid buildup of soluble
      salts. All samples showed a very high concentration of total P (1963.1 mg/kg -
      2644.1 mg/kg) with the plant available fraction ranging from 21.3% - 37.7% of the
      total P. All the heavy metals measured (Cr, Cu, Ni, Pb and Zn) were below the
      maximum permissible limits set by the U.S. Environmental Protection Agency.
      However, some of the poultry manure showed some level of phytotoxicity based on
      the plant bioassay, with some samples, recording a germination index less than
      50% for the different crops evaluated. However, this bioassay may not be
      conclusive and there is need to evaluate this phytotoxicity in real world field
      applications as there is paucity of information on this aspect regarding poultry
      manure. Such filed studies can be used to evaluate alternative strategies such as
      planting and harvest intervals between application of these manures and planting
      or harvesting. It is also suggested that further biodegradation through
      composting or vermicomposting may be required to improve nutrient content and
      reduce the presence of phytotoxic compounds in some of the poultry manures before
      use as soil amendments.

PMID- 29326989
TI  - Progressive calibration and averaging for tandem mass spectrometry statistical
      confidence estimation: Why settle for a single decoy?
AB  - Estimating the false discovery rate (FDR) among a list of tandem mass spectrum
      identifications is mostly done through target-decoy competition (TDC). Here we
      offer two new methods that can use an arbitrarily small number of additional
      randomly drawn decoy databases to improve TDC. Specifically, "Partial
      Calibration" utilizes a new meta-scoring scheme that allows us to gradually
      benefit from the increase in the number of identifications calibration yields and
      "Averaged TDC" (a-TDC) reduces the liberal bias of TDC for small FDR values and
      its variability throughout. Combining a-TDC with "Progressive Calibration" (PC),
      which attempts to find the "right" number of decoys required for calibration we
      see substantial impact in real datasets: when analyzing the Plasmodium falciparum
      data it typically yields almost the entire 17% increase in discoveries that "full
      calibration" yields (at FDR level 0.05) using 60 times fewer decoys. Our methods
      are further validated using a novel realistic simulation scheme and importantly,
      they apply more generally to the problem of controlling the FDR among discoveries
      from searching an incomplete database.

PMID- 29326990
TI  - A fluorescent microbead-based microfluidic immunoassay chip for immune cell
      cytokine secretion quantification.
AB  - Quantitative and dynamic analyses of immune cell secretory cytokines are
      essential for precise determination and characterization of the "immune
      phenotype" of patients for clinical diagnosis and treatment of immune-related
      diseases. Although multiple methods including the enzyme-linked immunosorbent
      assay (ELISA) have been applied for cytokine detection, such measurements remain
      very challenging in real-time, high-throughput, and high-sensitivity immune cell
      analysis. In this paper, we report a highly integrated microfluidic device that
      allows for on-chip isolation, culture, and stimulation, as well as sensitive and
      dynamic cytokine profiling of immune cells. Such a microfluidic sensing chip is
      integrated with cytometric fluorescent microbeads for real-time and multiplexed
      monitoring of immune cell cytokine secretion dynamics, consuming a relatively
      small extracted sample volume (160 nl) without interrupting the immune cell
      culture. Furthermore, it is integrated with a Taylor dispersion-based mixing unit
      in each detection chamber that shortens the immunoassay period down to less than
      30 minutes. We demonstrate the profiling of multiple pro-inflammatory cytokine
      secretions (e.g. interleukin-6, interleukin-8, and tumor necrosis factors) of
      human peripheral blood mononuclear cells (PBMCs) with a sensitivity of 20 pg ml-1
      and a sample volume of 160 nl per detection. Further applications of this
      automated, rapid, and high-throughput microfluidic immunophenotyping platform can
      help unleash the mechanisms of systemic immune responses, and enable efficient
      assessments of the pathologic immune status for clinical diagnosis and immune
      therapy.

PMID- 29326992
TI  - A Cu(ii) metal-organic framework with significant H2 and CO2 storage capacity and
      heterogeneous catalysis for the aerobic oxidative amination of C(sp3)-H bonds and
      Biginelli reactions.
AB  - A Cu(ii) metal-organic framework, {[Cu2(L)(H2O)2].(5DMF)(4H2O)}n (1), has been
      synthesized using an angular tetracarboxylic acid ligand (H4L) incorporating both
      trifluoromethyl (-CF3) and amine (-NH2) groups. Notably, the framework possesses
      high water and thermal stability. At atmospheric pressure, the activated
      framework 1' exhibits substantially high amounts of CO2 (35.5 and 20.8 wt% at 273
      and 298 K respectively) and H2 (1.72 wt% at 77 K) adsorption. Also, 1' exhibits
      excellent catalytic activity for the condensation-cyclization reaction between 2
      benzoyl pyridine and different benzylamines via oxidative amination of the C(sp3)
      H bond to form 1,3-diarylated imidazo[1,5-a]pyridines under mild aerobic
      conditions. In addition to this, 1' shows excellent heterogeneous catalytic
      activity in Biginelli reactions. The solid catalyst could be recycled several
      times without significant loss in the catalytic activities.

PMID- 29326991
TI  - A facile one-pot synthesis of acrylated hyaluronic acid.
AB  - The synthesis of acrylated hyaluronic acid (HA-A) normally requires 2 to 3 steps
      of modification, needs laborious purification and also increases the risks of HA
      degradation. Here, we report that the conjugation of acrylate groups to
      hyaluronic acid can be successfully achieved via a new facile one-pot approach.
      Two types of new HA-A hydrogels (via chemical or UV crosslinking) were developed
      and applied for 3D cell encapsulation.

PMID- 29326993
TI  - Turning double hydrophilic into amphiphilic: IR825-conjugated polymeric
      nanomicelles for near-infrared fluorescence imaging-guided photothermal cancer
      therapy.
AB  - Developing biocompatible and photodegradable photothermal agents (PTAs) holds
      great promise for potential clinical applications in photothermal cancer therapy.
      Herein, a new PTA was innovatively constructed by conjugating the hydrophobic
      near-infrared (NIR) heptamethine cyanine molecule IR825-NH2 with a double
      hydrophilic block copolymer methoxypoly(ethylene glycol)5k-block-poly(l-aspartic
      acid sodium salt)10 (abbreviated as PEG-PLD) via amine-carboxyl reaction. The as
      designed PEG-PLD(IR825) was amphiphilic and could self-assemble into polymeric
      nanomicelles in aqueous solutions. Benefiting from the chemical conjugation
      strategy, PEG-PLD(IR825) nanomicelles realized a considerably high drug loading
      rate (~21.0%) and substantially avoided the premature release of IR825 during
      systemic circulation. Confocal imaging revealed that the nanomicelles mainly
      located at mitochondria and endoplasmic reticulum after cellular internalization.
      In vitro photothermal therapy demonstrated the excellent cancer killing
      efficiency of PEG-PLD(IR825) nanomicelles due to their high light-to-heat
      conversion efficiency upon NIR laser irradiation. In addition, PEG-PLD(IR825)
      nanomicelles showed polarity-sensitive fluorescence at ~610 nm (under 552 nm
      excitation) and 830 nm (under 780 nm excitation), which was especially useful for
      both in vitro visible fluorescence imaging and in vivo near-infrared fluorescence
      imaging-guided photothermal therapy (PTT). At the in vivo level, PEG-PLD(IR825)
      nanomicelles exhibited an excellent tumor-homing ability and a long retention
      time in tumor tissues as evidenced by the in vivo fluorescence imaging results.
      The desirable properties of PEG-PLD(IR825) nanomicelles ensured their effective
      tumor ablation during PTT treatment. More importantly, the PEG-PLD(IR825)
      nanomicelles underwent degradation after laser irradiation, which ensured their
      post-treatment biosafety. Therefore, the nanomicelles are promising to serve as
      an efficient and safe PTA for imaging-guided photothermal cancer therapy.

PMID- 29326994
TI  - Single coating of zinc ferrite renders magnetic nanomotors therapeutic and stable
      against agglomeration.
AB  - Magnetic nanomotors with integrated theranostic capabilities can revolutionize
      biomedicine of the future. Typically, these nanomotors contain ferromagnetic
      materials, such that small magnetic fields can be used to maneuver and localize
      them in fluidic or gel-like environments. Motors with large permanent magnetic
      moments tend to agglomerate, which limits the scalability of this otherwise
      promising technology. Here, we demonstrate the application of a microwave
      synthesized ferrite layer to reduce the agglomeration of helical ferromagnetic
      nanomotors by an order of magnitude, which allows them to be stored in a
      colloidal suspension for longer than six months and subsequently be manoeuvred
      with undiminished performance. The ferrite layer also rendered the nanomotors
      suitable as magnetic hyperthermia agents, as demonstrated by their cytotoxic
      effects on cancer cells. The two functionalities were inter-related since higher
      hyperthermia efficiency required a denser suspension, both of which were achieved
      in a single microwave-synthesized ferrite coating.

PMID- 29326995
TI  - Alkene functionalization for the stereospecific synthesis of substituted
      aziridines by visible-light photoredox catalysis.
AB  - A novel strategy involving visible-light-induced functionalization of alkenes for
      the synthesis of substituted aziridines was developed. The readily prepared N
      protected 1-aminopyridinium salts were used for the generation of N-centered
      radicals. This approach allowed the synthesis of aziridines bearing various
      functional groups with excellent diastereoselectivity under mild conditions.
      Moreover, this protocol was successfully applied to prepare structurally diverse
      nitrogen-containing frameworks.

PMID- 29326996
TI  - Organocatalytic [3 + 2] cycloaddition of oxindole-based azomethine ylides with 3
      nitrochromenes: a facile approach to enantioenriched polycyclic spirooxindole
      chromane adducts.
AB  - An organocatalytic asymmetric [3 + 2] cycloaddition of oxindole-based azomethine
      ylides with 3-nitro-2H-chromenes has been developed. This reaction provides a
      facile approach to densely functionalized polycyclic spirooxindole-chromane
      adducts featuring four contiguous stereogenic centers, including two
      tetrasubstituted carbon centers. The products were obtained in high yields with
      good to excellent stereoselectivities (up to 99% yields, 96% ee and >20 : 1 dr).
      In addition, the spiro[pyrrolidine-2,3'-oxindole]-chromane adducts could be
      readily derivatized via simple oxidation and reduction treatment. A dual
      activation working model to illuminate the stereochemical course of the [3 + 2]
      cycloaddition event is proposed.

PMID- 29326997
TI  - Evidence of lying molecules in the structure of the most condensed phase of semi
      fluorinated alkane monolayers.
AB  - Semifluorinated alkanes are known to form peculiar nano-structured monolayers on
      the surface of water. A comprehensive analysis of in situ Grazing Incidence Small
      Angle X-ray Scattering (GISAXS) proves that the structure of their condensed
      phase consists of domains of upright molecules surrounded by lying down
      molecules. Such a model explains the non-coalescence of the domains and is in
      agreement with the high resolution AFM images of monolayers at the surfaces of
      solid substrates. The interaction of the lying molecule dipoles with the dipole
      of the water surface is proposed to explain the observed structuration.

PMID- 29326998
TI  - In situ development of amorphous Mn-Co-P shell on MnCo2O4 nanowire array for
      superior oxygen evolution electrocatalysis in alkaline media.
AB  - Exploitation of efficient and earth-abundant electrocatalysts for the oxygen
      evolution reaction (OER) is of great importance. Herein, we report that the
      formation of an amorphous Mn-Co-P shell on MnCo2O4 can boost its OER activity in
      alkaline media. The core-shell Mn-Co-P@MnCo2O4 nanowire array on Ti mesh (Mn-Co
      P@MnCo2O4/Ti) shows excellent electrochemical catalytic activity and requires an
      overpotential of 269 mV to drive 10 mA cm-2 in 1.0 M KOH, which is 93 mV less
      than that for the MnCo2O4 nanoarray. Notably, this catalyst also shows strong
      long-term electrochemical durability with its activity being maintained for at
      least 100 h and achieves a high turnover frequency of 1.06 s-1 at an
      overpotential of 450 mV.

PMID- 29326999
TI  - A semi-rigid isoindoline-derived nitroxide spin label for RNA.
AB  - A new isoindoline-derived benzimidazole nitroxide spin label, ImUm, was
      synthesized and incorporated into RNA oligoribonucleotides. ImUm is the first
      example of a conformationally unambiguous spin label for RNA, in which the
      nitroxide N-O bond lies on the same axis as the single bond used to attach the
      rigid isoindoline-based spin label to a uridine base. This results in minimal
      displacement of the nitroxide upon rotation of this single bond, which is a
      useful property for a label to be used for distance measurements. Continuous-wave
      (CW) EPR measurements of RNA duplexes containing ImUm indicate a restricted
      rotation around this single bond, presumably due to an intramolecular hydrogen
      bond between the benzimidazole N-H and O4 of the uracil. Orientation-selective
      pulsed electron-electron double resonance (PELDOR, also called double electron
      electron resonance, or DEER) distance measurements between two spin labels in two
      RNA duplexes showed in one case a strong orientation dependence, further
      confirming the restricted motion of the spin labels in RNA duplexes.

PMID- 29327000
TI  - Atomic charges for conformationally rich molecules obtained through a modified
      principal component regression.
AB  - A modification of the principal component regression model is proposed for
      obtaining a fixed set of atomic charges (referred to as dipole-derived charges)
      optimized for reproducing the dipole moment of a conformationally rich molecule,
      i.e., a molecule with multiple local minima on the potential energy surface. The
      method does not require any adjustable parameters and requires the geometries of
      conformers, their dipole moments and atomic polar tensor (APT) charges as the
      only input data. The fixed atomic charges generated by the method not only
      reproduce the molecular dipole moment in all the conformers accurately, but are
      also numerically close to the APT charges, thereby ensuring accurate reproduction
      of the dipole moment variations caused by small geometrical distortions (e.g., by
      vibrations) of the conformers. The proposed method has been applied to canonical
      2'-deoxyribonucleotides, the model DNA monomers, and the dipole-derived charges
      have been shown to outperform both the averaged APT and RESP charges in
      reproducing the dipole moments of large sets of conformers, thus demonstrating a
      potential usefulness of the dipole-derived charges as a 'reference point' for
      modeling polarization effects in conformationally rich molecules.

PMID- 29327001
TI  - Cumulative energy analysis of thermally-induced surface wrinkling of
      heterogeneously multilayered thin films.
AB  - Wrinkling is a well-known example of instability-driven surface deformation that
      occurs when the accumulated compressive stress exceeds the critical value in
      multilayered systems. A number of studies have investigated the instability
      conditions and the corresponding mechanisms of wrinkling deformation. Force
      balance analysis of bilayer systems, in which the thickness of the capping layer
      is importantly considered, has offered a useful approach for the quantitative
      understanding of wrinkling. However, it is inappropriate for multilayer wrinkling
      (layer number > 3) consisting of heterogeneous materials (e.g. polymer/metal or
      inorganic), in which the thickness variation in the substrate is also crucial.
      Therefore, to accommodate the additive characteristics of multilayered systems,
      we thermally treated tri- or quad-layer samples of polymer/metal multilayers to
      generate surface wrinkles and used a cumulative energy balance analysis to
      consider the individual contribution of each constituent layer. Unlike the
      composite layer model, wherein the thickness effect of the capping layer is
      highly overestimated for heterogenously stacked multilayers, our approach
      precisely reflects the bending energy contribution of the given multilayer
      system, with results that match well with experimental values. Furthermore, we
      demonstrate the feasibility of this approach as a metrological tool for simple
      and straightforward estimation of the thermomechanical properties of polymers,
      whereby a delicate change in the Young's modulus of a thin polymeric layer near
      its glass transition temperature can be successfully monitored.

PMID- 29327002
TI  - Charge separation properties of Ta3N5 photoanodes synthesized via a simple metal
      organic-precursor decomposition process.
AB  - Here, we successfully synthesized a Ta3N5 thin film using a simple metal-organic
      precursor decomposition process followed by its conversion to nitride and studied
      its photoelectrochemical (PEC) properties to understand charge separation on the
      surface. Newly synthesized Ta3N5 photoanodes showed a significant difference in
      the PEC activity in relation to the annealing temperature under ammonia flow,
      although similar light absorption properties or electronic states were obtained.
      Charge separation related PEC properties were analyzed using intensity modulated
      photocurrent density spectroscopy (IMPS) and photocurrent measurements in the
      absence/presence of scavengers. The charge transfer and recombination rate
      constants which are related to the photogenerated charge-separation dynamics on
      the Ta3N5 surface were found to be more sensitively influenced by the ammonia
      annealing temperatures, and low temperature (700  degrees C) treated Ta3N5 showed
      a fast recombination rate constant (kr). In addition, high-efficiency charge
      injection into the electrolyte on the surface was critically associated with the
      greatly enhanced photocurrent density of Ta3N5 synthesized at a higher
      temperature (900  degrees C) of ammonia annealing.

PMID- 29327003
TI  - Carbon dots as absorbance promoter probes for detection of Cu(ii) ions in aqueous
      solution: central composite design approach.
AB  - In this work, the use of carbon dots (CDs) as a complexing agent and sensitizer
      in a polymeric matrix for determination of copper(ii) by UV-vis spectroscopy is
      reported for the first time. A new and highly selective Schiff base, namely,
      (N',N'''E,N',N'''E)-N',N'''-((((2-hydroxypropane-1,3-diyl)bis(oxy))bis(2,1
      phenylene))bis(methan-ylylidene))di(isonicotinohydrazide) (NHBMDI), was also
      incorporated in the polymeric matrix. For the first time, the membrane
      composition of the proposed optical sensor including NHBMDI as the ionophore,
      tetraphenylborate (NaTPB) as the anionic additive, dibutyl phthalate (DBP) as the
      plasticizer and polyvinyl chloride (PVC) as the immobilizer was optimized through
      central composite design combined with the desirability function approach (DFA)
      because this method saves material and time consumption and is therefore cost
      effective. The synthesized CDs were characterized by transmission electron
      microscopy (TEM) and scanning electron microscopy (SEM). The fluorescence quantum
      yield of the synthesized CDs was found to be 6.4% by using quinine sulfate as the
      reference. The characterization of the prepared membrane sensor was investigated
      by field emission scanning electron microscope (FE-SEM) and atomic force
      microscopy (AFM).The response of the optode was based on the strong absorbance of
      NHBMDI and CDs upon exposure to Cu(ii) ions with the maximum wavelength at 371
      nm. The proposed sensor exhibited a linear response in the concentration range of
      1.2 * 10-6-4.56 * 10-5 mol L-1 with a detection limit of 7.1 * 10-7 mol L-1,
      which is lower than U.S. Environmental Protection Agency's defined limit (20
      MUM). Furthermore, the proposed optode displayed good selectivity toward Cu(ii)
      ions in comparison with common coexisting cations with satisfactory repeatability
      and reproducibility. The sensor was applied successfully for determination of
      copper(ii) ions in water samples.

PMID- 29327004
TI  - Photoinduced ICT vs. excited rotamer intercoversion in two quadrupolar
      polyaromatic N-methylpyridinium cations.
AB  - The excited state dynamics of two quadrupolar polyaromatic N-methylpyridinium
      cations have been fully investigated in order to acquire detailed information on
      their photo-induced behavior. The two molecules are symmetric push-pull compounds
      having a D-pi-A+-pi-D motif, with the same electron-acceptor central unit (A = N
      methylpyridinium) and two distinctive electron-donor polyaromatic side groups
      (D), namely naphthyl and pyrenyl substituents. Both molecules undergo charge
      transfer during the absorption, as revealed by a significant solvatochromism
      exhibited with solvent polarity, but the fate of their excited state was found to
      be markedly different. The careful analysis of the data gathered from femtosecond
      resolved fluorescence up-conversion and transient absorption experiments,
      supported by DFT quantum mechanical calculations and temperature-dependent
      stationary measurements, shows the leading role of intramolecular charge
      transfer, assisted by symmetry breaking, in the pyrenyl derivative and that of
      rotamer interconversion in the naphthtyl one. Both excited state processes are
      controlled by the viscosity rather than polarity of the solvent, and they occur
      during inertial solvation in low-viscous media and lengthening up to tens of
      picoseconds in highly viscous solvents.

PMID- 29327005
TI  - VIVO complexes with antibacterial quinolone ligands and their interaction with
      serum proteins.
AB  - Quinolone derivatives are among the most commonly prescribed antibacterials in
      the world and could also attract interest as organic ligands in the design of
      metal complexes with potential pharmacological activity. In this study, five
      compounds, belonging to the first (nalidixic acid or Hnal), second (ciprofloxacin
      or Hcip, and norfloxacin or Hnor) and third generation (levofloxacin or Hlev, and
      sparfloxacin or Hspar) of quinolones, were used as ligands to bind the VIVO2+
      ion. In aqueous solution, mono- and bis-chelated species were formed as a
      function of pH, with cis-[VOHxL2(H2O)]x+ and [VOHxL2]x+, x = 0-2, being the major
      complexes at pH 7.4. DFT calculations indicate that the most stable isomers are
      the octahedral OC-6-32 and the square pyramidal SPY-5-12, in equilibrium with
      each other. To the best of our knowledge, this is the first case that an
      equilibrium between a penta-coordinated square pyramidal complex and a hexa
      coordinated octahedral complex is observed in solution for ligands forming six
      membered chelated rings. Nalidixic acid forms the solid compound [VO(nal)2(H2O)],
      to which a cis-octahedral geometry was assigned. The interaction with 1
      methylimidazole (MeIm) causes a shift of the equilibrium SPY-5 + H2O ? OC-6
      toward the right after the formation of cis-[VOHxL2(MeIm)]x+, where MeIm replaces
      an equatorial water ligand. The study of the systems containing [VO(nal)2(H2O)]
      and the serum proteins - albumin (HSA), apo-transferrin (apo-hTf) and holo
      transferrin (holo-hTf) - indicates that HSA and holo-hTf form the mixed species
      {VO(nal)2}y(HSA) and {VO(nal)2}y(holo-hTf), where y = 1-3 denotes the number of
      VO(nal)2 moieties bound to accessible histidines (His105, His367, His510 for HSA,
      and His25, His349, His606 for holo-hTf), whereas apo-hTf yields VO(nal)2(apo-hTf)
      with the coordination of the His289 residue only. Docking calculations suggest
      that the specific conformation of apo-hTf and the steric hindrance of the cis
      VO(nal)2 moiety interfere with its interaction with all the surface His residues
      and the formation of a hydrogen bond network which could stabilize the binding
      sites.

PMID- 29327006
TI  - Spectrochemical analyses of growth phase-related bacterial responses to low
      (environmentally-relevant) concentrations of tetracycline and nanoparticulate
      silver.
AB  - Exposure to environmental insults generally occurs at low levels, making it
      challenging to measure bacterial responses to such interactions. Additionally,
      microbial behaviour and phenotype varies in differing bacterial types or growth
      phases, likely giving rise to growth- or species-specific responses to
      environmental stimuli. The present study applied a spectrochemical tool, infrared
      (IR) spectral interrogation coupled with multivariate analysis, to investigate
      the growth- and species-specific responses of two bacterial strains, Gram
      negative Pseudomonas fluorescens and Gram-positive Mycobacterium vanbaalenii, to
      low concentrations of tetracycline, nanoparticulate silver (AgNP) or mixtures
      thereof. Results indicate the tendency for tetracycline-induced biospectral
      alterations to occur in outer-cellular components, e.g., phospholipids or
      proteins, while AgNPs-induced changes are mainly associated with proteins (~964
      cm-1, ~1485 cm-1, ~1550 cm-1, ~1650 cm-1). The primary altered targets are
      correlated with bacterial membranes or outer-cellular components. Furthermore,
      significant lipid changes at 1705-1750 cm-1 were only present in P. fluorescens
      cells compared to M. vanbaalenii, owing to differences in cell wall structure
      between Gram-positive and -negative bacteria. This study also found distinct
      biospectral alterations in non-log phase compared to log phase, confirming
      bacterial growth-dependent responses to environmental exposures. It implies that
      previous studies on log phase only may underestimate the impacts from exposures
      of interest in situ, where bacteria stay in different growth stages. Our work
      proves the feasibility of biospectroscopy in determining bacterial responses to
      low-level environmental exposures in a fast and efficient manner, revealing
      sufficient biochemical information continuously through growth phases. As a
      nondestructive approach, biospectroscopy may provide deeper insights into the
      actual and in situ interactions between microbes and environmental stimuli,
      regardless of the exposure level, growth phase, or bacterial types.

PMID- 29327007
TI  - Contact laws between nanoparticles: the elasticity of a nanopowder.
AB  - Studies of the mechanical contact between nanometer-scale particles provide
      fundamental insights into the mechanical properties of materials and the validity
      of contact laws at the nanoscale which are still under debate for contact
      surfaces approaching atomic dimensions. Using in situ Brillouin light scattering
      under high pressure, we show that effective medium theories successfully predict
      the macroscopic sound velocities in nanopowders if one takes into account the
      cementation of the contacts Our measurements suggest the relevance of the
      continuum approach and effective medium theories to describe the contact between
      nanoparticles of diameters as small as 4 nm, i.e. with radii of contact of a few
      angstroms. In particular, we demonstrate that the mechanical properties of
      nanopowders strongly depend on the surface state of the nanoparticles. The
      presence of molecular adsorbates modifies significantly the contact laws.

PMID- 29327008
TI  - An upconversion nanoparticle-based fluorescence resonance energy transfer system
      for effectively sensing caspase-3 activity.
AB  - We report a new fluorescence resonance energy transfer (FRET) sensing platform
      for the sensitive detection of caspase-3 activity in vitro and in cells using
      NaGdF4:Yb3+,Er3+@NaGdF4 upconversion nanoparticles (UCNPs) as the energy donor
      and Rhodamine B (RB) as the energy acceptor. The phosphorylated RB-modified
      peptide containing a caspase-3 cleavage site and cell-penetrating peptide (CPP)
      motif (sequence, (RB)-DEVDGGS(p)GCGT(p)GRKKRRQRRRPQ) is immobilized on the UCNP
      surface via the strong coordination interaction between Gd3+ ions with phosphate.
      After the cleavage of DEVD by caspase-3, the RB is released from the UCNP surface
      and the reduced upconversion luminescence (UCL) is recovered. Under the optimum
      conditions, the recovery ratio of the UCL is linearly dependent on the caspase-3
      concentration within the range of 0.01 to 1000 pg mL-1 and with a limit of
      detection (LOD) of 0.01 pg mL-1 (S/N = 3). In particular, the as-proposed UCNP
      based FRET sensing platform has reasonable selectivity which is successfully
      employed to monitor caspase-3 activity in drug-induced apoptosis of HeLa cells.

PMID- 29327009
TI  - Fluorescent and magnetic anti-counterfeiting realized by biocompatible
      multifunctional silicon nanoshuttle-based security ink.
AB  - Herein, we present the first example of a silicon nanoshuttle-based security ink
      simultaneously featuring attractive optical and magnetic properties, suitable for
      fluorescent and magnetic anti-counterfeiting and encryption. Significantly, the
      information can be dual-encrypted through multi-color fluorescence and
      longitudinal (T1)/transverse (T2) relaxation contrast by using the silicon
      nanoshuttle-based security ink. We further demonstrate the feasibility of this
      high-performance ink for practical application in banknote anti-counterfeiting.

PMID- 29327010
TI  - DNA methylation assay using droplet-based DNA melting curve analysis.
AB  - DNA methylation is an epigenetic regulation of gene expression, which has drawn
      great attention in biomedical research due to its association with various
      diseases. A robust, inexpensive platform to detect and quantify the methylation
      status in a specific genomic region is necessary. In this study, an on-chip
      analytical technique of cytosine methylation with droplets in a microchannel is
      proposed. Genomic DNA samples are encapsulated into a series of droplets and
      transported through a detection region, where a stable temperature gradient is
      created. As the temperature is elevated from 60  degrees C to 85  degrees C, the
      DNA samples denature and the associated fluorescence signals decay, with the
      relationship being acquired as the melting curve. The droplets serve as discrete
      reactors for conducting DNA melting curve analysis in the liquid phase, thereby
      eliminating the need for immobilization of reagents. Due to a high heating rate
      and greater enhanced thermal stability, this microchip allows larger melting
      temperature differences for the samples at different percentages of methylated
      DNA. It has an enhanced discrimination ability and lower volume consumption,
      compared to the commercial qPCR machine. This chip enables quantification of the
      methylation levels of the pluripotent stem cell factor Oct-4 in its distal
      enhancer (DE) region, with a designed probe after bisulfite treatment and
      asymmetric PCR.

PMID- 29327011
TI  - Highly reversible and fast sodium storage boosted by improved interfacial and
      surface charge transfer derived from the synergistic effect of heterostructures
      and pseudocapacitance in SnO2-based anodes.
AB  - Sodium-ion batteries have attracted worldwide attention as potential alternatives
      for large scale stationary energy storage due to the rich reserves and low cost
      of sodium resources. However, the practical application of sodium-ion batteries
      is restricted by unsatisfying capacity and poor rate capability. Herein, a novel
      mechanism of improving both interfacial and surface charge transfer is proposed
      by fabricating a graphene oxide/SnO2/Co3O4 nanocomposite through a simple
      hydrothermal method. The formation of heterostructures between ultrafine SnO2 and
      Co3O4 could enhance the charge transfer of interfaces owing to the internal
      electric field. The pseudocapacitive effect, which is led by the high specific
      area and the existence of ultrafine nanoparticles, takes on a feature of fast
      faradaic surface charge-transfer. Benefiting from the synergistic advantages of
      the heterostructures and the pseudocapacitive effect, the as-prepared graphene
      oxide/SnO2/Co3O4 anode achieved a high reversible capacity of 461 mA h g-1 after
      80 cycles at a current density of 0.1 A g-1. Additionally, at a high current
      density of 1 A g-1, a high reversible capacity of 241 mA h g-1 after 500 cycles
      is obtained. A full cell coupled by the as-prepared graphene oxide/SnO2/Co3O4
      anode and the Na3V2(PO4)3 cathode was also constructed, which exhibited a
      reversible capacity of 310.3 mA h g-1 after 100 cycles at a current density of 1
      A g-1. This method of improving both interfacial and surface charge transfer may
      pave the way for the development of high performance sodium-ion batteries.

PMID- 29327012
TI  - Low-force spectroscopy on graphene membranes by scanning tunneling microscopy.
AB  - Two-dimensional atomically flat sheets with a high mechanical flexibility are
      very attractive as ultrathin membranes but are also inherently challenging for
      microscopic investigations. We report on a method using Scanning Tunneling
      Microscopy (STM) under ultra-high vacuum conditions for non-indenting low-force
      spectroscopy on micrometer-sized freestanding graphene membranes. The method is
      based on applying quasi-static voltage ramps with active feedback at low
      tunneling currents and ultimately relies on the attractive electrostatic force
      between the tip and the membrane. As a result a bulge-test scenario can be
      established. The convenience and simplicity of the method relies on the fact that
      the loading force and the membrane deflection detection are both provided
      simultaneously by the STM. This permits the continuous measurement of the stress
      strain relation. Electrostatic forces applied are typically below 1 nN and the
      membrane deflection is detected at sub-nanometer resolution. Experiments on
      single-layer graphene membranes with a strain of 0.1% reveal a two-dimensional
      elastic modulus E2D = 220 N m-1.

PMID- 29327013
TI  - Thienylene vinylene dimerization: from solution to self-assembled monolayer on
      gold.
AB  - The electrochemical and spectroelectrochemical studies of thienylene vinylene
      (TV) derivatives in the immobilized state are compared with the ones obtained in
      solution. The results highlight the exaltation of the dimerization process onto
      TV-based self-assembled monolayers, in which the pi interaction is maintained
      even after 75% dilution.

PMID- 29327015
TI  - A water-soluble, bay-functionalized perylenediimide derivative - correlating
      aggregation and excited state dynamics.
AB  - The aggregation and the photophysics of a water soluble perylenediimide (PDI)
      derivative that features two bromine substituents in the bay positions has been
      probed. Non-fluorescent aggregates were found to be present at concentrations of
      1.0 * 10-5 M. In situ small-angle X-ray scattering (SAXS) measurements and
      complementary molecular modeling showed the presence of PDI aggregates. In their
      singlet excited states, the PDI aggregates are characterized by distinct
      transient fingerprints and rapid deactivation, as revealed by pump-probe
      experiments on the femto-, pico-, nano-, and microsecond timescales. The product
      of this deactivation is a PDI triplet excited state. The efficiency of the
      triplet formation depends on the concentration, and hence on the degree of
      aggregation. Notably, for PDI concentrations in the range of the critical micelle
      concentration, the efficiency of intersystem crossing is close to zero. In short,
      we have demonstrated, for the first time, aggregation-induced formation of
      triplet excited states for PDI derivatives.

PMID- 29327014
TI  - Design of biomimetic substrates for long-term maintenance of alveolar epithelial
      cells.
AB  - There is a need to establish in vitro lung alveolar epithelial culture models to
      better understand the fundamental biological mechanisms that drive lung diseases.
      While primary alveolar epithelial cells (AEC) are a useful option to study mature
      lung biology, they have limited utility in vitro. Cells that survive demonstrate
      limited proliferative capacity and loss of phenotype over the first 3-5 days in
      traditional culture conditions. To address this limitation, we generated a novel
      physiologically relevant cell culture system for enhanced viability and
      maintenance of phenotype. Here we describe a method utilizing e-beam lithography,
      reactive ion etching, and replica molding to generate poly-dimethylsiloxane
      (PDMS) substrates containing hemispherical cavities that mimic the architecture
      and size of mouse and human alveoli. Primary AECs grown on these cavity
      containing substrates form a monolayer that conforms to the substrate enabling
      precise control over cell sheet architecture. AECs grown in cavity culture
      conditions remain viable and maintain their phenotype over one week.
      Specifically, cells grown on substrates consisting of 50 MUm diameter cavities
      remained 96 +/- 4% viable and maintained expression of surfactant protein C
      (SPC), a marker of type 2 AEC over 7 days. While this report focuses on primary
      lung alveolar epithelial cells, our culture platform is potentially relevant and
      useful for growing primary cells from other tissues with similar cavity-like
      architecture and could be further adapted to other biomimetic shapes or contours.

PMID- 29327016
TI  - Isoenergic modification of whey protein structure by denaturation and
      crosslinking using transglutaminase.
AB  - Transglutaminase (TG) catalyzes formation of covalent bonds between lysine and
      glutamine side chains and has applications in manipulation of food structure.
      Physical properties of a whey protein mixture (SPC) denatured either at elevated
      pH or by heat-treatment and followed by TG catalyzed crosslinking, have been
      characterised using dynamic light scattering, size exclusion chromatography,
      flourescence spectroscopy and atomic force microscopy. The degree of enzymatic
      crosslinking appeared higher for pH- than for heat-denatured SPC. The hydrophobic
      surface properties depended on the treatment, thus heating caused the largest
      exposure of the hydrophobic core of SPC proteins, which was decreased by
      crosslinking. The particle size of the treated SPC samples increased upon
      crosslinking by TG. Moreover, the particle morphology depended on the type of
      denaturing treatment, thus heat-treated SPC contained fibrillar structures, while
      pH-denatured SPC remained globular as documented by using atomic force
      microscopy. Finally, the in vitro digestability of the different SPC samples was
      assessed under simulated gastric and intestinal conditions. Notably heat
      treatment was found to lower the gastric digestion rate and enzymatic
      crosslinking reduced both the gastric and the intestinal rate of digestion. These
      characteristics of the various SPC samples provide a useful basis for design of
      isoenergic model foods applicable in animal and human studies on how food
      structure affects satiety.

PMID- 29327017
TI  - A significant role of non-thermal equilibrated electrons in the formation of
      deleterious complex DNA damage.
AB  - Although most of the radiation damage to genomic DNA could be rendered harmless
      using repair enzymes in a living cell, a certain fraction of the damage is
      persistent resulting in serious genetic effects, such as mutation induction. In
      order to understand the mechanisms of the deleterious DNA damage formation in
      terms of its earliest physical stage at the radiation track end, dynamics of low
      energy electrons and their thermalization processes around DNA molecules were
      investigated using a dynamic Monte Carlo code. The primary incident (1 keV)
      electrons multiply collide within 1 nm (equivalent to three DNA-base-pairs, 3bp)
      and generate secondary electrons which show non-Gaussian and non-thermal
      equilibrium distributions within 300 fs. On the other hand, the secondary
      electrons are mainly distributed within approximately 10 nm from their parent
      cations although approximately 5% of the electrons are localized within 1 nm of
      the cations owing to the interaction of their Coulombic fields. The mean electron
      energy is 0.7 eV; however, more than 10% of the electrons fall into a much lower
      energy region than 0.1 eV at 300 fs. These results indicate that pre-hydrated
      electrons are formed from the extremely decelerated electrons over a few nm from
      the cations. DNA damage sites comprising multiple nucleobase lesions or single
      strand breaks can therefore be formed by multiple collisions of these electrons
      within 3bp. This multiple damage site is hardly processed by base excision repair
      enzymes. However, pre-hydrated electrons can also be produced resulting in an
      additional base lesion (or a strand break) more than 3bp away from the multi
      damage site. These damage sites may be finally converted into a double strand
      break (DSB) when base excision enzymes process the additional base lesions. This
      DSB includes another base lesion(s) at their termini, and may introduce miss
      rejoining by DSB repair enzymes, and hence may result in biological effects such
      as mutation in surviving cells.

PMID- 29327018
TI  - The mechanism for the stabilization and surfactant properties of epitaxial
      silicene.
AB  - Using real-time in situ scanning tunneling microscopy and density functional
      theory simulations, we have studied the growth of Si films on Ag(111) beyond the
      silicene monolayer, evidencing the existence of metastable phases and an original
      growth mechanism. Above monolayer Si coverage, an initial structure forms, which
      is identified as an Ag-free Si bilayer with additional Si adatoms. With further
      deposition, this structure is replaced by a distinct bilayer structure covered by
      Si trimers and Ag atoms. The formation of these bilayers follows counterintuitive
      dynamics: they are partially inserted within the Ag substrate and form by
      expelling, from the underlying substrate, the atoms that reinsert below the
      adjacent silicene layer. The growth is therefore characterized by an unexpected
      "surfactant competition" between Ag and silicene: while silicene is a metastable
      surfactant for the Ag(111) surface, Ag plays the role of a surfactant for thicker
      diamond-like Si islands. In spite of being thermodynamically unfavoured, the
      silicene monolayer is, thus, a remarkably stable structure because of the high
      kinetic barrier for the growth of thicker layers.

PMID- 29327019
TI  - Using a novel rigid-fluoride polymer to control the interfacial thickness of
      graphene and tailor the dielectric behavior of poly(vinylidene fluoride
      trifluoroethylene-chlorotrifluoroethylene) nanocomposites.
AB  - Polymer nanocomposites based on conductive fillers for high performance
      dielectrics have attracted increasing attention in recent years. However, a
      number of physical issues are unclear, such as the effect of interfacial
      thickness on the dielectric properties of the polymer nanocomposites, which
      limits the enhancement of permittivity. In this research, two core-shell
      structured reduced graphene oxide (rGO)@rigid-fluoro-polymer conducting fillers
      with different shell thicknesses are prepared using a surface-initiated
      reversible-addition-fragmentation chain transfer polymerization method, which are
      denoted as rGO@PTFMS-1 with a thin shell and rGO@PTFMS-2 with a thick shell. A
      rigid liquid crystalline fluoride-polymer poly{5-bis[(4-trifluoro
      methoxyphenyl)oxycarbonyl]styrene} (PTFMS) is chosen for the first time to tailor
      the shell thicknesses of rGO via tailoring the degree of polymerization. The
      effect of interfacial thickness on the dielectric behavior of the P(VDF-TrFE
      CTFE) nanocomposites with rGO and modified rGO is studied in detail. The results
      demonstrate that the percolation threshold of the nanocomposites increased from
      0.68 vol% to 1.69 vol% with an increase in shell thickness. Compared to the
      rGO@PTFMS-1/P(VDF-TrFE-CTFE) composites, the rGO@PTFMS-2/P(VDF-TrFE-CTFE)
      composites exhibited a higher breakdown strength and a lower dielectric constant,
      which can be interpreted by interfacial polarization and the micro-capacitor
      model, resulting from the insulating nature of the rigid-polymer shell and the
      change of rGO's morphology. The findings provide an innovative approach to tailor
      dielectric composites, and promote a deeper understanding of the influence of
      interfacial region thickness on the dielectric performance.

PMID- 29327020
TI  - Magnetic properties of core-shell nanoparticles possessing a novel Fe(ii)-chromia
      phase: an experimental and theoretical approach.
AB  - Room-temperature ferrimagnetic and superparamagnetic properties, and the magnetic
      interactions between the core and shell, of our iron-incorporated chromia-based
      core shell nanoparticles (CSNs) have been investigated using a combination of
      experimental measurement and density functional theory (DFT) based calculations.
      We have synthesized CSNs having an epitaxial shell and well-ordered interface
      properties by utilizing our hydrothermal nanophase epitaxy (HNE) technique. The
      ferrimagnetic and superparamagnetic properties of the CSNs are manifested beyond
      room temperature and magnetic measurements reveal that the exchange bias
      interaction between the antiferromagnetic (AFM) core and ferrimagnetic (FiM)
      shell persists close to ambient temperature. The DFT calculations confirm the FiM
      ordering of the Fe-chromia shell. Our calculations show that the FiM ordering is
      associated with a band gap reduction, Fe-O d-p orbital hybridization, and AFM
      type Fe-Cr sigma type superexchange interaction in the alpha-Fe0.40Cr1.60O2.92
      shell of the CSNs. The novel magnetic core-shell nanoparticles possess a shell
      comprised of a metastable Fe(ii)-chromia phase, resulting in unique magnetic
      properties that make them ideal for magnetic device and medicinal applications.

PMID- 29327021
TI  - Formation of copper nanoparticles in LTL nanosized zeolite: spectroscopic
      characterization.
AB  - The state of copper species stabilized in nanosized LTL zeolite subjected to
      various post-synthesis treatments was unveiled by a range of spectroscopic
      techniques. FTIR and UV-Vis studies demonstrated that the reduction process of
      copper in the LTL nanosized zeolite leads to the formation of different species
      including Cu2+, Cu+ and Cu nanoparticles (Cu NPs). The adsorption of probe
      molecules (NO and CO) was used to selectively monitor the copper species in the
      LTL nanosized zeolite upon oxidation and reduction post-synthesis treatments.
      Both the Cu2+ and Cu+ species were probed by NO and CO, respectively. The amount
      of Cu+ in the LTL zeolite nanocrystals was about 43% as determined by FTIR, while
      the amount of Cu NPs was about 55% determined by the UV-Vis spectroscopic
      characterization. These results were complemented by EPR, 29Si and 63Cu MAS NMR
      spectroscopic data. The EPR spectroscopy was further applied to monitor the
      effective reduction of the Cu2+ species and their re-oxidation, while the 63Cu
      MAS NMR verified the presence of Cu NPs in the LTL nanosized zeolite crystals.

PMID- 29327022
TI  - On the approximation of independent pairs in diffusion kinetics: correlation of
      distances in a three-body system.
AB  - This study investigates the problem of diffusion kinetics in a three-body system,
      motivated by the theory of radiation chemical kinetics. The backward diffusion
      equation for the joint density of the distances is formulated, and an explicit
      formula for the infinitesimal covariance of two diffusing distances is derived.
      The Clifford-Green theorem is used to show how the infinitesimal covariance of
      two distances is linked to the covariance of the corresponding two squared
      distances as time evolves. In addition, computer simulations for the problem are
      presented, which indicate that hitting probabilities are also correlated. While
      the results indicate that more work is needed before a usable correction to the
      independence approximation is possible, clear progress has been made.

PMID- 29327023
TI  - A step towards understanding the beneficial influence of a LIPON-based artificial
      SEI on silicon thin film anodes in lithium-ion batteries.
AB  - In this work, we present a comprehensive study on the influence of lithium
      phosphorus oxynitride (LIPON) as a possible "artificial SEI layer" on the
      electrochemical performance of pure silicon (Si) thin film electrodes for a
      possible application in microbatteries or on-chip batteries. Si thin film anodes
      (140 nm) with and without an additional amorphous LIPON surface layer of
      different thicknesses (100-300 nm) were prepared by magnetron sputter deposition.
      The LIPON surface coating was characterized thoroughly by means of
      electrochemical impedance spectroscopy, Raman spectroscopy, X-ray photoelectron
      spectroscopy and atomic force microscopy. In situ electrochemical dilatometry and
      ex situ cross-section analysis of the electrodes after cycling could prove that
      the LIPON coating greatly diminishes the volume expansion of the Si electrode
      and, therefore, significantly improves the cycling stability and capacity
      retention. Furthermore, the LIPON coating remarkably reduces parasitic
      electrolyte decomposition reactions that originate from the Si volume expansion
      and contribute to the overall electrode volume expansion, as observed by the
      enhanced Coulombic efficiency over ongoing charge/discharge cycling. Overall,
      this article focuses on the preparation of optimized Si-based thin film
      electrodes in combination with LIPON solid electrolyte coatings for use in high
      energy lithium ion batteries.

PMID- 29327025
TI  - Unraveling the mechanical behaviour of hydrazine borane (NH2-NH2-BH3).
AB  - Crystalline B-N-H compounds of low molecular weight have been intensively
      investigated over the past two decades owing to their promises for chemical
      hydrogen storage. Hydrazine borane NH2-NH2-BH3 is one of the most recent examples
      of this family of materials. In the present work, we explored its structural
      behaviour under mechanical stimulus by synchrotron high pressure X-ray
      diffraction. It has been evidenced that hydrazine borane shows a gradual pressure
      induced decrease of its unit cell dimension and the process is reversible when
      the applied pressure is released. The compressibility of this material was
      established to be relatively low (high bulk modulus) and highly anisotropic. As
      revealed by molecular simulations based on Density Functional Theory
      calculations, the mechanical behaviour of NH2-NH2-BH3 was correlated to the
      pressure-induced changes of its crystal structure in terms of intra- and
      intermolecular bond lengths and angles parameters.

PMID- 29327024
TI  - A lithium-ion oxygen battery with a Si anode lithiated in situ by a Li3N
      containing cathode.
AB  - A practicable strategy has been developed to build a LixSi-O2 battery using an in
      situ formed Li-Si alloy anode based on the decomposition of Li3N pre-loaded in
      the cathode. The LixSi-O2 battery has achieved more than 100 stable charge
      discharge cycles with lower polarization than that using a lithium metal anode.

PMID- 29327026
TI  - FeCl3-catalyzed dimerization/elimination of 1,1-diarylalkenes: efficient
      synthesis of functionalized 4H-chromenes.
AB  - An efficient synthesis of valuable poly-substituted 4H-chromenes was developed
      via a [4 + 2] cycloaddition followed by the elimination of 1,1-diarylalkenes. The
      inexpensive FeCl3 salt has proven to be an efficient catalyst for this
      transformation. The commercial availability of the catalyst and reagents,
      together with a convenient procedure, makes this an attractive method for 4H
      chromene synthesis.

PMID- 29327027
TI  - Polymersomes with asymmetric membranes and self-assembled superstructures using
      pentablock quintopolymers resolved by electron tomography.
AB  - Polystyrene-block-poly(1,4-isoprene)-block-poly(dimethyl siloxane)-block
      poly(tert-butyl methacrylate)-block-poly(2-vinyl pyridine), PS-b-PI-b-PDMS-b
      PtBMA-b-P2VP, self-assembles in acetone into polymersomes with asymmetric
      (directional) PI-b-PDMS membranes. The polymersomes, in turn, self-assemble into
      superstructures. Analogically to supravesicular structures at a smaller length
      scale, we refer to them as suprapolymersome structures. Electron tomograms are
      shown to be invaluable in the structural assessment of such complex self
      assemblies.

PMID- 29327028
TI  - Transition metals and trace elements in the retinal pigment epithelium and
      choroid: correlative ultrastructural and chemical analysis by analytical electron
      microscopy and nano-secondary ion mass spectrometry.
AB  - Understanding the localisation and abundance of structural elements, trace
      elements and especially transition metals like Cu and Zn in ocular tissue
      sections is important for physiology, and also for the characterisation of
      diseases related to oxidative stress like age-related macular degeneration.
      Transition metal abundances were investigated in an aged donor eye by nano
      secondary ion mass spectrometry (nano-SIMS) elemental mapping using Cs+ and O-
      primary ions, respectively, and correlated to their respective mole fractions
      investigated by analytical electron microscopy (AEM). The ultrastructure of the
      tissue and the elemental composition of melanosomes of the choroid and RPE, and
      RPE lipofuscin and melanolipofuscin granules can adequately be investigated by
      nano-SIMS using the secondary ion maps. Melanosomes, 0.5-1 MUm in size, yield
      sulphur maps and maps of stored metals like calcium, sodium and copper.
      Lipofuscin shows especially high phosphorus signals. Elements with mole fractions
      of about 0.1 at%, e.g. for P and Cu, as investigated by AEM before, can be
      validated using simultaneous SIMS maps with an estimated lateral resolution of 66
      nm with typical acquisition times of 30 minutes for each area of interest.
      However, Zn (0.19 at%) was not detected by SIMS. Nano-SIMS imaging of CN-, PO2-,
      S-, Cu-, Ca+, Fe+ and Na+ ions provides excellent detection limits demonstrating
      the possibilities for chemical mapping with high-sensitivity trace element
      detection and reduced acquisition times. Quantification of nano-SIMS data was
      achieved by correlating mole fractions obtained by AEM to secondary ions per
      pixel obtained by nano-SIMS. Both methods yield the melanin type in melanosomes
      and trace metal storage.

PMID- 29327029
TI  - Bio-inspired robust non-iridescent structural color with self-adhesive amorphous
      colloidal particle arrays.
AB  - Here we propose a new method for constructing highly color fast non-iridescent
      structural color materials by assembling self-adhesive poly-dopamine coated SiO2
      nanoparticles (PDA@SiO2) for amorphous colloidal arrays through a "spraying"
      process. Simply by alkaline vapor treatment, the adhesive forces and fastness of
      the amorphous colloidal arrays were significantly improved. This was demonstrated
      by lap shear tests of tape tearing and cohesive failure as well as a series of
      fastness tests like sandpaper abrasion, finger wiping and ultrasonic cleaning.
      Besides, the strengthening fastness reaction could occur on different substrates,
      including glass, metals, polymers and paper, regardless of their chemical and
      physical properties. Moreover, the structural color of the PDA@SiO2 arrays was
      bright due to the broadband absorption of PDA, and was tunable according to the
      size, PDA content and arrangement of the PDA@SiO2 arrays.

PMID- 29327030
TI  - Novel ruthenium and iridium complexes of N-substituted carbazole as triplet
      photosensitisers.
AB  - Novel mono- and di-nuclear Ru(ii) and Ir(iii) complexes, bearing a modified
      carbazole moiety are synthesised. In comparison to their mononuclear analogues,
      the homonuclear diatomic complexes (RuCRu and IrCIr), in which the carbazole
      containing-ligand functions as a bridge, display increased absorbance in the
      visible region, and give rise to higher singlet oxygen quantum yields.

PMID- 29327031
TI  - A thin CdSe shell boosts the electron transfer from CdTe quantum dots to
      methylene blue.
AB  - CdTe core and CdTe/CdSe core/shell quantum dots (QD) are investigated with steady
      state and time-resolved spectroscopic methods. The coating of the CdTe core with
      a 0.7 nm thick CdSe shell shifts the lowest exciton absorption band to the red by
      more than 70 nm making the CdTe/CdSe QD an interesting candidate for application
      in solar energy conversion. Femtosecond transient absorption measurements are
      applied to study the photoinduced electron transfer (ET) to the molecular
      acceptor methylene blue (MB). ET times after single excitation of the QD are
      determined for different MB : QD ratios. The ET reaction is significantly faster
      in the case of the MB-CdTe/CdSe QD complexes, indicative of an altered charge
      distribution in the photoexcited heterostructure with a higher electron density
      in the CdSe shell. As a result of the efficient absorption of incoming light and
      the faster ET reaction, the amount of reduced MB in the time resolved experiments
      is higher for CdTe/CdSe QD compared to CdTe QD.

PMID- 29327032
TI  - Three-dimensional Volumetric Analysis of 3 Fat-Processing Techniques for Facial
      Fat Grafting: A Randomized Clinical Trial.
AB  - Importance: Autologous fat grafting has revolutionized the field of facial soft
      tissue augmentation, despite a lack of standardization. Objective data are needed
      to arrive at consensus regarding the best technique for optimal volume retention.
      Objective: To compare 3 fat-processing techniques with 3-dimensional (3-D)
      technology to explore the optimal fat-processing technique for improving the
      volume retention of grafted fat. Design, Setting, and Participants: From
      September 2015 to December 2016, patients with facial asymmetry were treated by
      initial facial fat grafting at the Plastic Surgery Hospital, Chinese Academy of
      Medical Sciences and Peking Union Medical College. Sixty-three patients (21 per
      group) were randomized to 1 of 3 fat-processing techniques: sedimentation,
      centrifugation, and cotton pad filtration. Patients underwent 3-D scanning
      preoperatively and at 1, 3, 6, and 12 months postoperatively. Patients who did
      not complete preoperative or postoperative follow-up and 3-D imaging were
      excluded from the analysis. Intervention: Autologous fat grafting to correct
      facial asymmetry. Main Outcomes and Measures: The percentage volume maintenance
      of each fat-processing technique was measured with 3-D software and analyzed with
      variance analysis. Results: Of the 63 randomized patients, 30 (7 men, 23 women;
      mean [SD] age at surgery, 22.2 [8.0] years) completed follow-up. The mean (SD)
      percentage volume maintenance of the 3 groups at 1, 3, 6, and 12 months
      postoperatively was, respectively, 49% (4%), 45% (3%), 43% (3%), and 41% (3%) for
      the cotton pad filtration group; 41% (3%), 38% (4%), 36% (4%), and 34% (3%) for
      the centrifugation group; and 37% (4%), 34% (4%), 31% (3%), and 31% (3%) for
      sedimentation group. The variance analysis showed that the cotton pad filtration
      group demonstrated a statistically significant higher percentage volume
      maintenance in comparison with the centrifugation and sedimentation groups.
      Conclusions and Relevance: The use of 3-D technology provides an objective and
      accurate way to evaluate different fat-processing techniques. Autologous fat
      processed by cotton pad filtration had a significant higher volume retention than
      did that processed by centrifugation and sedimentation technique. Trial
      Registration: chictr.org.cn Identifier: ChiCTR-IOR-14005599. Level of Evidence:
      1.

PMID- 29327033
TI  - Disorganization of Inner Retina and Outer Retinal Morphology in Diabetic Macular
      Edema.
AB  - Importance: In diabetic macular edema (DME), identification of baseline markers
      on spectral-domain optical coherence tomography (SD-OCT) and their association
      with severity of diabetic retinopathy (DR) might aid in disease management and
      the design of future trials. Objective: To examine associations between DR
      severity, retinal morphology on SD-OCT, and visual acuity in participants with
      DME. Design, Setting, and Participants: This cross-sectional observational case
      series was conducted at a single tertiary care referral center. Demographics,
      visual acuity, SD-OCT, and color fundus photographs of 80 individuals with DME
      (102 eyes) seen between December 28, 2013, and April 30, 2014, were analyzed
      between May 1 and July 31, 2016. Main Outcomes and Measures: Features captured on
      SD-OCT and thickness metrics. On SD-OCT we graded type and shape of DME, shape
      and presence of septae within the intraretinal cystoid abnormalities, presence of
      hyperreflective dots and foci, integrity of the external limiting membrane and
      ellipsoid zone, presence and extent of disorganization of the inner retinal
      layers (DRIL), and the status of the vitreomacular interface and epiretinal
      membrane. We measured retinal thickness at the fovea and at the site of maximum
      pathology, choroidal thickness at the fovea, and 1000 MUm temporal and nasal to
      the fovea. Color photographs were graded to derive a DR severity stage. Results:
      The mean (SD) age was 63 (11) years, and 30 participants (37.5%) were women. The
      odds of having DRIL were greater in eyes with disrupted external limiting
      membrane (odds ratio [OR], 4.4; 95% CI, 1.6-12.0; P = .003), disrupted ellipsoid
      zone (OR, 2.7; 95% CI, 1.0-7.2; P = .03), presence of epiretinal membrane (OR,
      2.8; 95% CI, 1.0-7.4; P = .03), and increase in retinal thickness at the fovea
      (OR, 1.6; 95% CI, 1.1-2.2; P < .001). Occurrence of DRIL was more likely in eyes
      with proliferative DR (OR, 7.3; 95% CI, 1.7-31.4; P = .007). Mean visual acuity
      decreased by approximately 4.7 letters for each 100-MUm increase in the average
      global DRIL (95% CI, -7.9 to 1.4; P = .006). Conclusions and Relevance: An
      association was found between DRIL and disruption of the outer retina and
      increasing DR severity. Further longitudinal studies seem warranted to determine
      whether DRIL is a clinically relevant noninvasive morphological marker in eyes
      with DME.

PMID- 29327034
TI  - The Rise and Fall of Mandatory Cardiac Bundled Payments.

PMID- 29327035
TI  - Recurrent Monocular Vision Loss and an Ocular Mass.

PMID- 29327036
TI  - Facial Pain and Diplopia in a Young Boy.

PMID- 29327039
TI  - Efficacy and Toxic Effects of Cancer Immunotherapy Combinations-A Double-edged
      Sword.

PMID- 29327040
TI  - A Surgical Procedure Grid for Safety and Operating Room Communication in
      Multisite Surgery.

PMID- 29327042
TI  - Transsaccadic memory of multiple spatially variant and invariant object features.
AB  - Transsaccadic memory is a process by which remembered object information is
      updated across a saccade. To date, studies on transsaccadic memory have used
      simple stimuli-that is, a single dot or feature of an object. It remains unknown
      how transsaccadic memory occurs for more realistic, complex objects with multiple
      features. An object's location is a central feature for transsaccadic updating,
      as it is spatially variant, but other features such as size are spatially
      invariant. How these spatially variant and invariant features of an object are
      remembered and updated across saccades is not well understood. Here we tested how
      well 14 participants remembered either three different features together
      (location, orientation, and size) or a single feature at a time of a bar either
      while fixating either with or without an intervening saccade. We found that the
      intervening saccade influenced memory of all three features, with consistent
      biases of the remembered location, orientation, and size that were dependent on
      the direction of the saccade. These biases were similar whether participants
      remembered either a single feature or multiple features and were not observed
      with increased memory load (single vs. multiple features during fixation trials),
      confirming that these effects were specific to the saccade updating mechanisms.
      We conclude that multiple features of an object are updated together across eye
      movements, supporting the notion that spatially invariant features of an object
      are bound to their location in memory.

PMID- 29327041
TI  - Common constraints limit Korean and English character recognition in peripheral
      vision.
AB  - The visual span refers to the number of adjacent characters that can be
      recognized in a single glance. It is viewed as a sensory bottleneck in reading
      for both normal and clinical populations. In peripheral vision, the visual span
      for English characters can be enlarged after training with a letter-recognition
      task. Here, we examined the transfer of training from Korean to English
      characters for a group of bilingual Korean native speakers. In the pre- and
      posttests, we measured visual spans for Korean characters and English letters.
      Training (1.5 hours * 4 days) consisted of repetitive visual-span measurements
      for Korean trigrams (strings of three characters). Our training enlarged the
      visual spans for Korean single characters and trigrams, and the benefit
      transferred to untrained English symbols. The improvement was largely due to a
      reduction of within-character and between-character crowding in Korean
      recognition, as well as between-letter crowding in English recognition. We also
      found a negative correlation between the size of the visual span and the average
      pattern complexity of the symbol set. Together, our results showed that the
      visual span is limited by common sensory (crowding) and physical (pattern
      complexity) factors regardless of the language script, providing evidence that
      the visual span reflects a universal bottleneck for text recognition.

PMID- 29327043
TI  - Association of Oral Microbiome With Risk for Incident Head and Neck Squamous Cell
      Cancer.
AB  - Importance: Case-control studies show a possible relationship between oral
      bacteria and head and neck squamous cell cancer (HNSCC). Prospective studies are
      needed to examine the temporal relationship between oral microbiome and
      subsequent risk of HNSCC. Objective: To prospectively examine associations
      between the oral microbiome and incident HNSCC. Design, Setting, and
      Participants: This nested case-control study was carried out in 2 prospective
      cohort studies: the American Cancer Society Cancer Prevention Study II Nutrition
      Cohort (CPS-II) and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening
      Trial (PLCO). Among 122 004 participants, 129 incident patient cases of HNSCC
      were identified during an average 3.9 years of follow-up. Two controls per
      patient case (n = 254) were selected through incidence density sampling, matched
      on age, sex, race/ethnicity, and time since mouthwash collection. All
      participants provided mouthwash samples and were cancer-free at baseline.
      Exposures: Oral microbiome composition and specific bacterial abundances were
      determined through bacterial 16S rRNA gene sequencing. Overall oral microbiome
      composition and specific taxa abundances were compared for the case group and the
      control group, using PERMANOVA and negative binomial generalized linear models,
      respectively, controlling for age, sex, race, cohort, smoking, alcohol, and oral
      human papillomavirus-16 status. Taxa with a 2-sided false discovery rate (FDR)
      adjusted P-value (q-value) <.10 were considered significant. Main Outcomes and
      Measures: Incident HNSCC. Results: The study included 58 patient cases from CPS
      II (mean [SD] age, 71.0 [6.4] years; 16 [27.6%] women) and 71 patient cases from
      PLCO (mean [SD] age, 62.7 [4.8] years; 13 [18.3%] women). Two controls per
      patient case (n = 254) were selected through incidence density sampling, matched
      on age, sex, race/ethnicity, and time since mouthwash collection. Head and neck
      squamous cell cancer cases and controls were similar with respect to age, sex,
      and race. Patients in the case group were more often current tobacco smokers,
      tended to have greater alcohol consumption (among drinkers), and to be positive
      for oral carriage of papillomavirus-16. Overall microbiome composition was not
      associated with risk of HNSCC. Greater abundance of genera Corynebacterium (fold
      change [FC], 0.58; 95% confidence interval [CI], 0.41-0.80; q = .06) and Kingella
      (FC, 0.63; 95% CI, 0.46-0.86; q = .08) were associated with decreased risk of
      HNSCC, potentially owing to carcinogen metabolism capacity. These findings were
      consistent for both cohorts and by cohort follow-up time. The observed
      relationships tended to be stronger for larynx cancer and for individuals with a
      history of tobacco use. Conclusions and Relevance: This study demonstrates that
      greater oral abundance of commensal Corynebacterium and Kingella is associated
      with decreased risk of HNSCC, with potential implications for cancer prevention.

PMID- 29327046
TI  - Optical Coherence Tomographic Analysis of the Optic Nerve Head and Surrounding
      Structures in Space Flight-Associated Neuro-ocular Syndrome.

PMID- 29327044
TI  - Association of the Lung Immune Prognostic Index With Immune Checkpoint Inhibitor
      Outcomes in Patients With Advanced Non-Small Cell Lung Cancer.
AB  - Importance: Derived neutrophils/(leukocytes minus neutrophils) ratio (dNLR) and
      lactate dehydrogenase (LDH) level have been correlated with immune checkpoint
      inhibitor (ICI) outcomes in patients with melanoma. Objective: To determine
      whether pretreatment dNLR and LDH are associated with resistance to ICIs in
      patients with advanced non-small cell lung cancer (NSCLC). Design, Setting, and
      Participants: Multicenter retrospective study with a test (n = 161) and a
      validation set (n = 305) treated with programmed death 1/programmed death ligand
      1 (PD-1/PD-L1) inhibitors in 8 European centers, and a control cohort (n = 162)
      treated with chemotherapy only. Complete blood cell counts, LDH, and albumin
      levels were measured before ICI treatment. A lung immune prognostic index (LIPI)
      based on dNLR greater than 3 and LDH greater than upper limit of normal (ULN) was
      developed, characterizing 3 groups (good, 0 factors; intermediate, 1 factor;
      poor, 2 factors). Main Outcomes and Measures: The primary end point was overall
      survival (OS). Secondary end points were progression-free survival (PFS) and
      disease control rate (DCR). Results: In the pooled ICI cohort (N = 466), 301
      patients (65%) were male, 422 (90%) were current or former smokers, and 401 (87%)
      had performance status of 1 or less; median age at diagnosis was 62 (range, 29
      86) years; 270 (58%) had adenocarcinoma and 159 (34%) had squamous histologic
      subtype. Among 129 patients with PD-L1 data, 96 (74%) had PD-L1 of at least 1% by
      immunohistochemical analysis, and 33 (26%) had negative results. In the test
      cohort, median PFS and OS were 3 (95% CI, 2-4) and 10 (95% CI, 8-13) months,
      respectively. A dNLR greater than 3 and LDH greater than ULN were independently
      associated with OS (hazard ratio [HR] 2.22; 95% CI, 1.23-4.01 and HR, 2.51; 95%
      CI, 1.32-4.76, respectively). Median OS for poor, intermediate, and good LIPI was
      3 months (95% CI, 1 month to not reached [NR]), 10 months (95% CI, 8 months to
      NR), and 34 months (95% CI, 17 months to NR), respectively, and median PFS was
      2.0 (95% CI, 1.7-4.0), 3.7 (95% CI, 3.0-4.8), and 6.3 (95% CI, 5.0-8.0) months
      (both P < .001). Disease control rate was also correlated with dNLR greater than
      3 and LDH greater than ULN. Results were reproducible in the ICI validation
      cohort for OS, PFS, and DCR, but were nonsignificant in the chemotherapy cohort.
      Conclusions and Relevance: Pretreatment LIPI, combining dNLR greater than 3 and
      LDH greater than ULN, was correlated with worse outcomes for ICI, but not for
      chemotherapy, suggesting that LIPI can serve as a potentially useful tool when
      selecting ICI treatment, raising the hypothesis that the LIPI might be useful for
      identifying patients unlikely to benefit from treatment with an ICI.

PMID- 29327045
TI  - Serial In-Office Intralesional Steroid Injections in Airway Stenosis.
AB  - Importance: Endoscopic dilation is the mainstay treatment strategy for subglottic
      and proximal tracheal stenosis (SGS/PTS). Its major limitation is restenosis
      requiring repeated surgery. Intralesional steroid injection (ISI) is a promising
      adjunctive treatment aimed at prolonging the effects of dilation. Objective: To
      evaluate the association of serial in-office ISI after endoscopic dilation with
      surgery-free interval (SFI) in adults with SGS/PTS. Design, Setting, and
      Participants: A retrospective study of adults with SGS/PTS who underwent at least
      2 consecutive in-office ISI at the University of Southern California, Keck School
      of Medicine, over a 3-year period was conducted. Exposure: Serial ISI with
      triamcinolone 40 mg/mL using topical anesthesia, spaced 3 to 6 weeks apart. Main
      Outcomes and Measures: Surgery-free interval, number of dilations, need for open
      airway surgery, decannulation rate, and adverse events. Patients with previous
      dilations and sufficient follow-up time were included in a comparative analysis
      of SFI before and after ISI. The Mann-Whitney U test was applied for comparisons.
      Results: Twenty-four patients met eligibility criteria. Mean (SD) age was 50.1
      (15.1) years; 18 (75%) were female. Ten (42%) patients had idiopathic, 8 (33%)
      had traumatic, and 6 (25%) had rheumatologic-related SGS/PTS. Mean (SD) follow-up
      time was 32.3 (33.4) months. Patients underwent mean (SD) 4.08 (1.91) injections.
      Seventeen (71%) patients have not undergone further surgery after ISI. Mean (SD)
      SFI was 17.8 (12.8) months overall and was 15.7 (10.6) months for idiopathic,
      13.8 (9.9) for traumatic, and 26.7 (16.9) for rheumatologic-related SGS/PTS.
      Twenty-one (88%) patients underwent dilation(s) prior to ISI. Among patients who
      fulfilled eligibility criteria for comparison of SFI before and after ISI, SFI
      improved from 10.1 months before, to 22.6 months after ISI (mean difference, 12.5
      months; 95% CI, -2.1 to 27.2 months). Three of 6 patients (all with traumatic
      SGS/PTS) presenting with a tracheotomy were decannulated. No patients required
      open airway surgery after ISI. There were no adverse events associated with ISI.
      Conclusions and Relevance: Serial in-office ISI are safe and well-tolerated in
      adults with SGS/PTS. This technique can reduce the surgical burden on these
      patients and may obviate the need for future airway intervention.

PMID- 29327048
TI  - Retinoblastoma With Endophytic and Exophytic Features.

PMID- 29327049
TI  - Rosette-Shaped Cataract Due to Lightning Injury.

PMID- 29327047
TI  - Histopathological and Inflammatory Features of Chronically Discharging Open
      Mastoid Cavities: Secondary Analysis of a Randomized Clinical Trial.
AB  - Importance: Many patients with an open radical mastoid cavity experience therapy
      resistant otorrhea. Little is known about the underlying histopathological
      substrate of unstable cavities and the correlation with treatment failure.
      Objective: To study the histopathological and inflammatory features of
      chronically discharging open radical mastoid cavities and the influence of
      different treatments. Design, Setting, and Participants: This secondary analysis
      of a randomized clinical trial was a histopathology study of tissue samples of a
      cohort of 30 patients with a chronically discharging open mastoid cavity. Samples
      were taken from the cavities, which were treated with either honey gel or
      conventional eardrops in a tertiary center between 2012 and 2013. Tissue staining
      was performed in May 2014; final computer analysis/correlation studies were
      performed in June 2016. Main Outcomes and Measures: Differences of epithelial
      tissue coverage, infiltration of T cells (CD3, CD4, CD8) and macrophage (CD68,
      isoenzyme nitric oxide synthase, arginase 1) (sub-)populations, infection status,
      and the correlation with clinical presentation. Results: There were 30 patients
      (24 [80%] male; mean [SD] age, 59 [14] years). Cavities were covered with either
      stratified squamous (keratinized) epithelium (n = 10), respiratory columnar
      epithelium (n = 9), or granulation tissue (n = 10). The presence of respiratory
      epithelium was associated with lower treatment success (posttreatment VAS
      improvement of 3.1 [95% CI, 0.5 to 5.8] for discomfort and 3.6 [95% CI, 0.2 to
      6.9] for otorrhea in the group with granulation tissue coverage vs 4.9 [95% CI,
      0.2 to 9.6] and 5.8 [95% CI, -0.1 to 11.6] in the group with squamous
      [keratinized] epithelium coverage and 1.4 [95% CI, -1.2 to 4.1] and 2.5 [95% CI, 
      1.3 to 6.2] in the group with respiratory columnar epithelium coverage). In all 3
      tissue types of cavity-covering tissues, T-cell infiltrates consisted of helper T
      cells and cytotoxic T cells, together with a lower number of macrophages. The
      immunopositivity for isoenzyme nitric oxide synthase and arginase 1 was high and
      not restricted to a macrophage subpopulation, but seen in various cell types.
      Inflammatory infiltrations varied strongly in all 3 tissue modalities.
      Conclusions and Relevance: Discharging open mastoid cavities can be classified
      histologically into 3 different types, based on their coverage: squamous
      epithelium, respiratory epithelium, or granulation tissue. Treatment is less
      successful in cavities covered with respiratory epithelium, possibly explained by
      the status of bacterial infection and local immunological differences.

PMID- 29327050
TI  - Ocular Inflammation Associated With Fibers From Eyelash Extensions.

PMID- 29327051
TI  - Primary Orbital Amyloidosis.

PMID- 29327054
TI  - Trends in Visual Health Inequalities in Childhood Through Associations of Visual
      Function With Sex and Social Position Across 3 UK Birth Cohorts-Reply.

PMID- 29327056
TI  - Neoadjuvant Systemic Therapy for Breast Cancer: Searching for More Effectively
      Curative Therapies.

PMID- 29327055
TI  - Comparing Neoadjuvant Nab-paclitaxel vs Paclitaxel Both Followed by Anthracycline
      Regimens in Women With ERBB2/HER2-Negative Breast Cancer-The Evaluating Treatment
      With Neoadjuvant Abraxane (ETNA) Trial: A Randomized Phase 3 Clinical Trial.
AB  - Importance: Studies of neoadjuvant chemotherapy regimens using anthracyclines
      followed by taxanes have reported a doubling of pathological complete remission
      (pCR) rates compared with anthracycline-based regimens alone. A reverse sequence
      did not reduce activity. Nab-paclitaxel is an albumin-bound nanoparticle of
      paclitaxel that allows for safe infusion without premedication, and its use led
      to a significantly higher rate of pCR in the GeparSepto trial. Objective: To
      determine whether nab-paclitaxel improves the outcomes of early and locally
      advanced human epidermal growth factor receptor 2 (ERBB2/HER2)-negative breast
      cancer compared with paclitaxel when delivered in a neoadjuvant setting. Design,
      Setting, and Participants: In this multicenter, open-label study, in
      collaboration with Grupo Espanol de Investigacion en Cancer de Mama (GEICAM) and
      Breast Cancer Research Center-Western Australia (BCRC-WA), patients with newly
      diagnosed and centrally confirmed ERBB2/HER2-negative breast cancer were
      recruited. Participants were randomly allocated to paclitaxel, 90 mg/m2 (349
      patients), or nab-paclitaxel, 125 mg/m2 (346 patients). The 2 drugs were given on
      weeks 1, 2, and 3 followed by 1 week of rest for 4 cycles before 4 cycles of an
      anthracycline regimen per investigator choice. Main Outcomes and Measures: The
      primary end point was the rate of pCR, defined as absence of invasive cells in
      the breast and axillary nodes (ie, ypT0/is ypN0) at the time of surgery. A
      secondary end point was to assess tolerability and safety of the 2 regimens.
      Results: From May 2013 to March 2015, 814 patients were registered to the study;
      695 patients met central confirmation eligibility and were randomly allocated to
      receive either paclitaxel (349), or nab-paclitaxel (346) (median age, 50 years;
      range, 25-79 years). The intention-to-treat analysis of the primary end point pCR
      revealed that the improved pCR rate after nab-paclitaxel (22.5%) was not
      statistically significant compared with paclitaxel (18.6%; odds ratio [OR], 0.77;
      95% CI, 0.52-1.13; P = .19). Overall, 38 of 335 patients (11.3%) 11.3% of
      patients had at least 1 serious adverse event in the paclitaxel arm and 54 of 337
      patient (16.0%) in the nab-paclitaxel arm. Peripheral neuropathy of grade 3 or
      higher occurred in 6 of 335 patients (1.8%) and in 15 of 337 (4.5%),
      respectively. Conclusions and Relevance: The improved rate of pCR after nab
      paclitaxel was not statistically significant. The multivariate analysis revealed
      that tumor subtype (triple-negative vs luminal B-like) was the most significant
      factor (OR, 4.85; 95% CI, 3.28-7.18) influencing treatment outcome. Trial
      Registration: clinicaltrials.gov Identifier: NCT01822314.

PMID- 29327058
TI  - Trends in Visual Health Inequalities in Childhood Through Associations of Visual
      Function With Sex and Social Position Across 3 UK Birth Cohorts.

PMID- 29327057
TI  - Distinguishing Uveitis Secondary to Sarcoidosis From Idiopathic Disease: Cardiac
      Implications.
AB  - Importance: Idiopathic disease is the most frequent diagnosis in a uveitis
      clinic. The need to distinguish sarcoidosis from idiopathic uveitis is
      controversial. However, cardiac involvement in sarcoidosis can be life
      threatening. Objective: To report a series of patients with uveitis and cardiac
      sarcoidosis to illustrate the importance of categorizing the causes of uveitis.
      Design, Setting, and Participants: This retrospective observational case series
      reviewed the medical records of 249 patients with uveitis who were referred to
      the Casey Eye Institute between July 1, 2008, and February 28, 2017. Main
      Outcomes and Measures: We describe patients who initially received a diagnosis of
      idiopathic uveitis but subsequently received a diagnosis of sarcoidosis. Clinical
      data, including ophthalmologic findings, were collected. We summarized the number
      of patients who initially presented with idiopathic uveitis, the number of
      patients who recived a classification of idiopathic uveitis after evaluation, the
      number of patients who underwent chest computed tomography or an
      electrocardiogram, and the number of patients with ocular sarcoidosis. Results:
      Of 33 patients with sarcoidosis, 21 (63.6%) were women and the mean (SD) age was
      53.5 (13.8) years. Of 249 patients, the referring diagnosis was idiopathic
      uveitis for 179 (72%). After history, examination, and laboratory testing, 127
      (51%) were still considered to have idiopathic disease. Fifty-three of the 179
      patients (30%) with idiopathic disease underwent chest computed tomography
      scanning. A diagnosis of presumed sarcoidosis, usually on the basis of a chest
      computed tomography scan, was made in 19 patients (36.2%). As 14 patients (5.6%)
      were previously known to have sarcoidosis, 33 patients (13.3%) were evaluated
      with definite or presumed ocular sarcoidosis. We obtained electrocardiograms as a
      screen for cardiac sarcoidosis on 14 (42.4%) of these patients. Nine patients
      with abnormal electrocardiogram results were referred to cardiologists. Four of
      the 19 patients (21.1%) who were referred for idiopathic uveitis but subsequently
      received a diagnosis of presumed sarcoidosis were found to have episodes of
      ventricular tachycardia that required implantable cardiac defibrillators.
      Distinguishing ocular sarcoidosis from idiopathic uveitis had potentially life
      saving implications for these patients. Conclusions and Relevance: The present
      case series shows the potential utility of distinguishing sarcoidosis-associated
      uveitis from idiopathic uveitis. We suggest that patients older than 40 years
      with a history of idiopathic uveitis be evaluated with chest computed tomography
      and an electrocardiogram if sarcoidosis is suggested on ophthalmic examination.

PMID- 29327059
TI  - Immunotherapy and Symptomatic Radiation Necrosis in Patients With Brain
      Metastases Treated With Stereotactic Radiation.

PMID- 29327060
TI  - Optical Coherence Tomography Analysis of the Optic Nerve Head and Surrounding
      Structures in Long-Duration International Space Station Astronauts.
AB  - Importance: After long-duration spaceflight, morphological changes in the optic
      nerve head (ONH) and surrounding tissues have been reported. Objective: To
      develop methods to quantify ONH and surrounding tissue changes using preflight
      and postflight optical coherence tomographic scans of the ONH region. Design,
      Setting, and Participants: Two separate analyses were done on retrospective data,
      with the first comparing a preflight group with a control group, followed by
      preflight to postflight analysis. All astronaut data were collected on the same
      instrument and maintained by the National Aeronautics and Space Administration
      (NASA) Lifetime Surveillance of Astronaut Health. Control data were all collected
      at the University of Houston. Participants were 15 astronauts who had previously
      been on an approximately 6-month long-duration mission and had associated
      preflight and postflight ONH scans. The control group consisted of 43 individuals
      with no history of ocular pathology or microgravity exposure. Development of
      algorithms and data analysis were performed between 2012 and 2015. Main Outcomes
      and Measures: The optical coherence tomography data were analyzed using custom
      MATLAB programs (MathWorks) in which the Bruch membrane opening (BMO) was
      manually delineated and used as a reference for all morphological measures. The
      retinal pigment epithelium (RPE) position 2 mm from the center of the BMO was
      used to calculate the BMO height. Global and quadrant total retinal thickness and
      retinal nerve fiber layer (RNFL) thickness were calculated for elliptical annular
      regions referenced to the BMO. The standard circumpapillary circular scan was
      used to quantify RNFL and choroidal thickness. Results: Among 15 astronauts (mean
      [SD] age at preflight evaluation, 48.7 [4.0] years) in this retrospective study,
      the BMO was recessed in preflight astronauts compared with healthy controls and
      deepened after long-duration microgravity exposure (median change, -9.9 MUm; 95%
      CI of difference, -16.3 to 3.7 MUm; P = .03). After long-duration missions, there
      was an increase in total retinal thickness to 1000 MUm and RNFL to 500 MUm from
      the BMO. Circumpapillary RNFL thickness increased by a median of 2.9 MUm (95% CI
      of difference, 1.1-4.4 MUm; P < .01), and there was no change in choroidal
      thickness (median change, 9.3 MUm; 95% CI of difference, -12.1 to 19.6 MUm; P =
      .66). Conclusions and Relevance: After long-duration microgravity exposure, there
      are disc edema-like changes in the morphology of the ONH and surrounding tissue.
      The methods developed to analyze the ONH and surrounding tissue can be useful for
      assessing longitudinal changes and countermeasures in astronauts, as well as
      potentially for terrestrial disc edema causes.

PMID- 29327061
TI  - EGFR-TKI-Associated Interstitial Pneumonitis in Nivolumab-Treated Patients With
      Non-Small Cell Lung Cancer.
AB  - Importance: Nivolumab and epidermal growth factor receptor-tyrosine kinase
      inhibitors (EGFR-TKIs) are now the standard-of-care therapies in non-small cell
      lung cancer (NSCLC). Although EGFR-TKIs are well understood and have well-defined
      safety profiles, our experience with immune checkpoint inhibitors is still
      growing, particularly regarding the use of combinations of different classes of
      antitumor agents, including both the concomitant and sequential use of such
      agents. Objective: To determine whether nivolumab increases EGFR-TKI-associated
      interstitial pneumonitis (IP). Design, Setting, and Participants: A database
      study of 20 516 participants with NSCLC in the US Food and Drug Administration
      Adverse Event Reporting System (FAERS) database, performed between April 2015 and
      March 2017. Main Outcomes and Measures: We compared the incidence of EGFR-TKI
      associated IP in patients receiving and not receiving nivolumab treatment.
      Results: The mean (SD) age of participants treated with EGFR-TKI, with and
      without nivolumab, was 64.4 (15.5) and 68.9 (11.8) years, respectively, and the
      proportion of men was 40.0% and 53.8%, respectively. Of the 20 516 participants
      with NSCLC, 985 cases (4.80%; 95% CI, 4.51-5.10) developed IP. Of 5777 patients
      treated with EGFR-TKI, 265 developed IP (4.59%; 95% CI, 4.06-5.16). Of 70
      patients treated with both EGFR-TKI and nivolumab, 18 developed IP (25.7%; 95%
      CI, 16.0-37.6). The adjusted odds ratio for an interaction between EGFR-TKI and
      nivolumab was 4.31 (95% CI, 2.37-7.86; P < .001), suggesting the existence of an
      interaction. When we further stratified the patients by treatment with and
      without nivolumab, the odds ratio of EGFR-TKI-associated IP in cases with and
      without nivolumab treatment was 5.09 (95% CI, 2.87-9.03) and 1.22 (95% CI, 1.00
      1.47), respectively. Conclusions and Relevance: We found a higher proportion of
      reports of IP for nivolumab in combination with EGFR-TKI vs treatment with either
      drug alone. Owing to the limitations of this study, the results warrant further
      confirmation. However, careful consideration should be given to the possibility
      of an increased risk of IP when EGFR-TKI is administered in combination with
      nivolumab, including concomitant and sequential use, and careful monitoring for
      IP is recommended.

PMID- 29327062
TI  - An Erythematous Papular Rash on the Left Flank of a 31-year-old Woman: A Quiz.

PMID- 29327063
TI  - Systemic Inflammation and Evidence of a Cardio-splenic Axis in Patients with
      Psoriasis.
AB  - The spleen is thought to play a role in atherosclerosis-associated immunity and
      cardiovascular research has indicated the existence of a cardio-splenic axis. The
      aim of this study was to assess splenic 18F-fluorodeoxyglucose uptake as a
      measure of systemic inflammation in patients with untreated psoriasis compared
      with historical controls assessed by positron emission tomography-computed
      tomography. Patients with moderate-to-severe psoriasis (n = 12, age 61.4 +/- 4.1
      years, 83% men, mean  Psoriasis Area Severity Index score of 14.5) and controls
      (n = 23, age 60.4 +/- 4.5 years, 87% men) were included in the study. Splenic
      inflammation was measured using the background-corrected spleen-liver-ratio (SLR)
      based on mean standardized uptake values. Mean +/- SD SLR was increased in
      patients with psoriasis compared with controls (0.94 +/- 0.11 vs. 0.82 +/- 0.08;
      p = 0.001). SLR was significantly associated with aortic inflammation. These
      results support the existence of systemic inflammation in patients with
      psoriasis, and provide the rationale for a mechanistic link between psoriasis
      driven inflammation and cardiovascular comorbidity through a spleen
      atherosclerotic axis.

PMID- 29327064
TI  - Eyelid Dermatitis as a Side Effect of Interleukin-17A Inhibitors in Psoriasis.

PMID- 29327065
TI  - Blood Predictive Biomarkers for Nivolumab in Advanced Melanoma.
AB  - Nivolumab response rate is 40% in metastatic melanoma. Few studies have evaluated
      pre-treatment biomarkers predictive of response. The aim of this study was to
      identify potential peripheral blood biomarkers associated with survival in
      patients with advanced melanoma treated with nivolumab. All advanced melanoma
      cases treated with anti-programmed cell death protein 1 (anti-PD1) over a 3-year
      period in the Dermato-Oncology Department, Nantes, France were identified. For
      each case, 9 potential blood biomarkers were identified. Bivariate and
      multivariate analyses, adjusted for the American Joint Committee on Cancer (AJCC)
      classification stage, Eastern Cooperative Oncology Group (ECOG) performance
      status, lactate dehydrogenase (LDH) level and failure to respond to first-line
      therapy, were used to test the association between biomarkers and overall
      survival (primary outcome) or progression-free survival (secondary outcome).
      Increased monocyte count, leukocyte/lymphocyte ratio and neutrophil/lymphocyte
      ratio were significantly associated with decreased overall survival after
      bivariate and multivariate analyses. Increased monocyte count was also
      significantly associated with decreased progression-free survival. These blood
      variables are easily measured and could help to predict patient response before
      the introduction of anti-PD1 therapy.

PMID- 29327066
TI  - Ramucirumab-induced Multiple Haemangiomas of the Skin: Two Case Reports.

PMID- 29327068
TI  - The specific effect of gallic acid on Escherichia coli biofilm formation by
      regulating pgaABCD genes expression.
AB  - Escherichia coli (E. coli) is associated with an array of health-threatening
      contaminations, some of which are related to biofilm states. The pgaABCD-encoded
      poly-beta-1,6-N-acetyl-D-glucosamine (PGA) polymer plays an important role in
      biofilm formation. This study was conducted to determine the inhibitory effect of
      gallic acid (GA) against E. coli biofilm formation. Minimal inhibitory
      concentration (MIC) and minimal bactericidal concentration (MBC) values of GA
      against planktonic E. coli were 0.5 and 4 mg/mL, and minimal biofilm inhibitory
      concentration and minimal biofilm eradication concentration values of GA against
      E. coli in biofilms were 2 and 8 mg/mL, respectively. Quantitative crystal violet
      staining of biofilms and ESEM images clearly indicate that GA effectively, dose
      dependently inhibited biofilm formation. CFU counting and confocal laser scanning
      microscopy measurements showed that GA significantly reduced viable bacteria in
      the biofilm. The contents of polysaccharide slime, protein, and DNA in the E.
      coli biofilm also decreased. qRT-PCR data showed that at the sub-MIC level of GA
      (0.25 mg/mL) and expression of pgaABC genes was downregulated, while pgaD gene
      expression was upregulated. The sub-MBC level of GA (2 mg/mL) significantly
      suppressed the pgaABCD genes. Our results altogether demonstrate that GA
      inhibited viable bacteria and E. coli biofilm formation, marking a novel approach
      to the prevention and treatment of biofilm-related infections in the food
      industry.

PMID- 29327067
TI  - Overexpression of Nogo receptor 3 (NgR3) correlates with poor prognosis and
      contributes to the migration of epithelial cells of nasopharyngeal carcinoma
      patients.
AB  - : Lymph node metastasis (N classification) is one of the most important
      prognostic factors of nasopharyngeal carcinoma (NPC), and nerve involvement is
      associated with the transition of the N category in NPC patients. Although the
      nervous system has been reported to participate in many types of cancer
      progression, its functions in NPC progression remains unknown. Through analysis
      of gene profiling data, we demonstrate an enrichment of genes associated with
      neuronal development and differentiation in NPC tissues and cell lines. Among
      these genes, Nogo receptor 3 (NgR3), which was originally identified in the
      nervous system and plays a role in nerve development and regeneration, was
      inappropriately overexpressed in NPC cells and tissues. Immunohistochemical
      analysis demonstrated that the overexpression of NgR3 was correlated with poor
      prognosis in NPC patients. Overexpression of NgR3 promoted, and knocking down
      NgR3 inhibited, NPC cell migration and invasion in vitro and metastasis in vivo.
      The ability of NgR3 to promote cell migration was triggered by the downregulation
      of E-cadherin and enhanced cytoskeletal rearrangement and cell polarity, which
      were correlated with the activation of focal adhesion kinase (FAK). Collectively,
      NgR3 is a novel indicator of poor outcomes in NPC patients and plays an important
      role in driving the progression of NPC. These results suggest a potential link
      between the nervous system and NPC progression. KEY MESSAGES: Genes involved in
      the neuronal biological process are enriched in nasopharyngeal carcinoma.
      Overexpression of NgR3 correlates with poor prognosis of nasopharyngeal
      carcinoma. NgR3 promotes NPC cell migration by downregulating E-cadherin. NgR3
      promotes NPC cell polarity and enhances the formation of NPC cell pseudopodia by
      activating FAK/Src pathway.

PMID- 29327069
TI  - [Tarsal tunnel syndrome after hip operation].

PMID- 29327070
TI  - [Open repair of gluteus medius and minimus tendons tears with double-row
      technique : Clinical and radiological results].
AB  - BACKGROUND: Operative refixation is a new therapeutic option in cases of failed
      conservative treatment for trochanteric pain syndrome (TPS) and lesions of the
      hip abductors in magnetic resonance imaging (MRI). OBJECTIVE: Evaluation of the
      clinical and radiological results after open gluteus medius and minimus tendon
      reconstruction with a double-row technique was carried out. MATERIAL AND METHODS:
      Patients with failed conservative treatment for TPS and confirmed lesions of the
      hip abductors in MRI were treated by open hip abductor tendon reconstruction with
      a double-row technique. The patients were evaluated preoperatively and
      postoperatively (minimum follow-up 12 months) using the modified Harris hip score
      (mHHS) and a subjective score (subjective hip value, SHV). Preoperative and
      postoperative MRI evaluation included measurement of hip abductor muscle diameter
      and cross-sectional area as well as fatty degeneration. RESULTS: In this study 12
      consecutive cases of open reconstruction of the hip abductor tendons were
      included. There was a significant improvement in the mHHS. In one case the
      patient showed an atraumatic rupture in the proximal anchor row. The MRI showed a
      significant improvement in muscle diameter and cross-sectional area for the
      gluteus medius muscle of the affected and the contralateral side, while the
      degree of fatty degeneration did not improve. The fatty degeneration showed a
      significant correlation with the postoperative results in the mHHS and the SHV.
      CONCLUSION: Operative reconstruction of lesions in the hip abductor tendons is a
      therapy option with significant improvement of patient satisfaction and
      functional scores as well as muscle diameter and cross-sectional area for the
      gluteus medius. The degree of fatty degeneration and possible differential
      diagnoses need to be taken into consideration.

PMID- 29327072
TI  - Naproxen Is Transformed Via Acetogenesis and Syntrophic Acetate Oxidation by a
      Methanogenic Wastewater Consortium.
AB  - Over-the-counter pharmaceutical compounds can serve as microbial substrates in
      wastewater treatment processes as well as in the environment. The metabolic
      pathways and intermediates produced during their degradation, however, are poorly
      understood. In this study, we investigate an anaerobic wastewater community that
      metabolizes naproxen via demethylation. Enriched cultures, established from
      anaerobic digester inocula receiving naproxen as the sole carbon source,
      transformed naproxen to 6-O-desmethylnaproxen (DMN) within 22 days. Continual
      enrichment and culture transfer resulted in consistent demethylation of naproxen
      with no loss of DMN observed. Methane was generated at 0.83 mmol per 1 mmol
      transformed naproxen. In addition to naproxen, the consortium readily
      demethylated syringic acid and vanillic acid. DNA analysis revealed a community
      of acetogenic bacteria and syntrophic acetate oxidizing archaea. Combined with
      the biotransformation data, this suggests the enriched consortium performs
      aromatic O-demethylation through a syntrophic relationship between specific
      acetogens, acetate oxidizers, and methanogens. The proposed model of carbon
      transfer through the anaerobic food web highlights the significance of linked
      community interactions in the anaerobic transformation of aromatic O-methyl
      compounds such as naproxen.

PMID- 29327074
TI  - Liver Tract Sealing with Hep-PlugTM Sealing System Improves Haemorrhage Control
      for Patients Undergoing Transhepatic Procedures.

PMID- 29327073
TI  - Azospirillum brasilense Increases CO2 Fixation on Microalgae Scenedesmus
      obliquus, Chlorella vulgaris, and Chlamydomonas reinhardtii Cultured on High CO2
      Concentrations.
AB  - Mutualism interactions of microalgae with other microorganisms are widely used in
      several biotechnological processes since symbiotic interaction improves
      biotechnological capabilities of the microorganisms involved. The interaction of
      the bacterium Azospirillum brasilense was assessed with three microalgae genus,
      Scenedesmus, Chlorella, and Chlamydomonas, during CO2 fixation under high CO2
      concentrations. The results in this study have demonstrated that A. brasilense
      maintained a mutualistic interaction with the three microalgae assessed,
      supported by the metabolic exchange of indole-3-acetic acid (IAA) and tryptophan
      (Trp), respectively. Besides, CO2 fixation increased, as well as growth and cell
      compound accumulation, mainly carbohydrates, in each microalgae evaluated,
      interacting with the bacterium. Overall, these results propose the mutualism
      interaction of A. brasilense with microalgae for improving biotechnological
      processes based on microalgae as CO2 capture and their bio-refinery capacity.

PMID- 29327071
TI  - Diseases of complement dysregulation-an overview.
AB  - Atypical hemolytic uremic syndrome (aHUS), C3 glomerulopathy (C3G), and
      paroxysmal nocturnal hemoglobinuria (PNH) are prototypical disorders of
      complement dysregulation. Although complement overactivation is common to all,
      cell surface alternative pathway dysregulation (aHUS), fluid phase alternative
      pathway dysregulation (C3G), or terminal pathway dysregulation (PNH) predominates
      resulting in the very different phenotypes seen in these diseases. The mechanism
      underlying the dysregulation also varies with predominant acquired autoimmune
      (C3G), somatic mutations (PNH), or inherited germline mutations (aHUS)
      predisposing to disease. Eculizumab has revolutionized the treatment of PNH and
      aHUS although has been less successful in C3G. With the next generation of
      complement therapeutic in late stage development, these archetypal complement
      diseases will provide the initial targets.

PMID- 29327075
TI  - Phase II Study of Sorafenib Combined with Concurrent Hepatic Arterial Infusion of
      Oxaliplatin, 5-Fluorouracil and Leucovorin for Unresectable Hepatocellular
      Carcinoma with Major Portal Vein Thrombosis.
AB  - BACKGROUND: Sorafenib is recommended for the first-line treatment of advanced
      hepatocellular carcinoma (HCC). However, the median progression-free survival
      (PFS) of patients with HCC and major portal vein tumor thrombosis treated with
      sorafenib monotherapy is no more than 3 months. A prospective single-arm phase II
      study was conducted to determine whether adding hepatic arterial infusion
      chemotherapy of oxaliplatin, 5-fluorouracil and leucovorin to sorafenib could
      improve on these results. METHODS: Thirty five patients were treated with
      sorafenib 400 mg orally twice a day, oxaliplatin 85 mg/m2 HAI on day 1,
      leucovorin 400 mg/m2 HAI on days 1, and 5-fluorouracil 2800 mg/m2 on days 1 and
      2, repeated every 21 days. The primary end point was the 3-month PFS rate.
      RESULTS: The 3-, 6-, and 12-month PFS rates were 82.9, 51.4, and 22.9%,
      respectively. The median PFS and overall survival was 6.7 and 13.2 months,
      respectively. The objective response rate was 40%, and the disease control rate
      was 77.1% by RECIST criteria. Five (14.3%) patients achieved conversion to
      complete resection after the study treatment, and one of them experienced a
      pathological complete response. Treatment-related deaths did not occur. Grade 3-4
      toxicities consisted of increases in aspartate aminotransferase (31.4%), hand
      foot syndrome (17.1%), thrombocytopenia (14.3%), and neutropenia (8.6%).
      CONCLUSIONS: The combination treatment met the pre-specified end point of a 3
      month progression free survival rate exceeding 65% and was clinical tolerable.
      The merits of this approach need to be established with a phase III trial.
      Clinical trial number http://ClinicalTrials.gov (No. NCT02981498).

PMID- 29327076
TI  - Arms Down Cone Beam CT Hepatic Angiography Performance Assessment: Vascular
      Imaging Quality and Imaging Artifacts.
AB  - INTRODUCTION: The practice of positioning patients' arms above the head during
      catheter-injected hepatic arterial phase cone beam CT (A-CBCT) imaging has been
      inherited from standard CT imaging due to image quality concerns, but interrupts
      workflow and extends procedure time. We sought to assess A-CBCT image quality and
      artifacts with arms extended above the head versus down by the side. METHODS: We
      performed an IRB approved retrospective evaluation of reformatted and 3D-volume
      rendered images from 91 consecutive A-CBCTs (43 arms up, 48 arms down) acquired
      during hepatic tumor arterial embolization procedures. Two interventional
      radiologists reviewed all A-CBCT imaging and assigned vessel visualization scores
      (VVS) from 1 to 5, ranging from non-diagnostic to optimal visualization. Streak
      artifacts across axial images were rated from 1 to 3 based on resulting image
      quality (none to significant). Presence of respiratory or cardiac motion during
      acquisition, body mass index and radiation dose area product (DAP) were also
      recorded and analyzed. Univariate and multivariate analyses were used to assess
      the impact of arm position on VVS and imaging artifacts. RESULTS: VVS were not
      significantly associated with arm position during A-CBCT imaging. One reader
      reported more streak artifacts across axial images in the arms down group (p =
      0.005). DAP was not statistically different between the groups (23.9 Gy cm2 [6.1
      73.4] arms up, 26.1 Gy cm2 [4.2-102.6] arms down, p = 0.54). CONCLUSION: A-CBCT
      angiography performed with the arms above the head is not superior for clinically
      relevant hepatic vascular visualization compared to imaging performed with the
      arms by the patient's side.

PMID- 29327077
TI  - Combined PD-1 and JAK1/2 inhibition in refractory primary mediastinal B-cell
      lymphoma.

PMID- 29327080
TI  - Editorial Board of Biological Cybernetics: Advances in Computational
      Neuroscience.

PMID- 29327079
TI  - Endoscopic third ventriculostomy for hydrocephalus in osteopetrosis: a case
      report and review of the literature.
AB  - INTRODUCTION: There are very few reports in the literature associating in
      hydrocephalus in osteopetrosis. As a complication of shunt procedure, there are
      two reports on shunt malfunction due to osseous overgrowth at the burr hole in
      patients with osteopetrosis. We herein report a case of osteopetrosis with
      hydrocephalus that was successfully treated with endoscopic third ventriculostomy
      (ETV). CASE REPORT: At 5 months of age, a male patient presented with
      developmental delay. Head computed tomography (CT) demonstrated triventricular
      hydrocephalus with a cerebellar tonsillar herniation. At 7 months of age, he
      underwent suboccipital decompression with decompression of the foramen magnum.
      The hydrocephalus did not improve postoperatively, and the patient was
      transferred to our hospital. At 12 months of age, the hydrocephalus was
      successfully treated with ETV. The postoperative period was uneventful.
      Postoperative CT demonstrated an improvement in the ventricle size. CONCLUSIONS:
      The etiology of hydrocephalus in osteopetrosis is not completely understood;
      however, there have been several reports in which ETV was effective. ETV should
      be considered the treatment of choice for hydrocephalus in osteopetrosis, as it
      avoids the characteristic shunt complications that can occur in patients with
      osteopetrosis.

PMID- 29327081
TI  - Neutrophils in viral infection.
AB  - Neutrophils are the first wave of recruited immune cells to sites of injury or
      infection and are crucial players in controlling bacterial and fungal infections.
      Although the role of neutrophils during bacterial or fungal infections is well
      understood, their impact on antiviral immunity is much less studied. Furthermore,
      neutrophil function in tumor pathogenesis and cancer treatment has recently
      received much attention, particularly within the context of oncolytic virus
      infection where neutrophils produce antitumor cytokines and enhance oncolysis. In
      this review, multiple functions of neutrophils in viral infections and immunity
      are discussed. Understanding the role of neutrophils during viral infection may
      provide insight into the pathogenesis of virus infections and the outcome of
      virus-based therapies.

PMID- 29327082
TI  - Evaluation of committed and primitive cord blood progenitors after expansion on
      adipose stromal cells.
AB  - Umbilical cord blood mononuclear fraction is a valuable source of hematopoietic
      stem and progenitor cells (CB HSPCs). The rarity of this population is a serious
      limitation of its application in cell therapy. Ex vivo expansion enables to
      significantly amplify the number of hematopoietic precursors of different
      commitment. Here, we expand CB MNCs in co-culture with human adipose tissue
      derived stromal cells (ASCs) to enrich HSPCs and describe phenotypic features of
      newly formed hematopoietic populations. The CD34+-HSPCs demonstrated 6-fold
      enrichment with 9000 CFUs per 50 * 103 HSPCs on average. A part of the floating
      HSPCs were bearing lineage markers, while others were primitive precursors (CD133
      /CD34+). Among ASC-associated HSPCs, two subsets of cord blood-borne cells were
      revealed: SD90+/SD45- and SD90+/SD45+. The proportion of CD3+/CD8+ and NK-T as
      well as CD25+ and HLA-DR+ T cells among SD90+/SD45- cells was significantly
      higher compared to MNCs and floating HSPCs. More than 80% of CD45+/SD90+ HSPCs
      were identified as late primitive precursors (CD133-/CD34+). Thus, CB MNC
      expansion in the presence of ASCs provides the generation of both lineage
      committed lymphoid progenitors and CD34+/CD133- primitive HSPCs. Substantially
      enriched with primitive precursors, ASC-associated HSPCs could be considered as a
      perspective tool for a long-term restoration of hematopoiesis in various
      hematologic disorders.

PMID- 29327083
TI  - R-loops: targets for nuclease cleavage and repeat instability.
AB  - R-loops form when transcribed RNA remains bound to its DNA template to form a
      stable RNA:DNA hybrid. Stable R-loops form when the RNA is purine-rich, and are
      further stabilized by DNA secondary structures on the non-template strand.
      Interestingly, many expandable and disease-causing repeat sequences form stable R
      loops, and R-loops can contribute to repeat instability. Repeat expansions are
      responsible for multiple neurodegenerative diseases, including Huntington's
      disease, myotonic dystrophy, and several types of ataxias. Recently, it was found
      that R-loops at an expanded CAG/CTG repeat tract cause DNA breaks as well as
      repeat instability (Su and Freudenreich, Proc Natl Acad Sci USA 114, E8392-E8401,
      2017). Two factors were identified as causing R-loop-dependent breaks at CAG/CTG
      tracts: deamination of cytosines and the MutLgamma (Mlh1-Mlh3) endonuclease,
      defining two new mechanisms for how R-loops can generate DNA breaks (Su and
      Freudenreich, Proc Natl Acad Sci USA 114, E8392-E8401, 2017). Following R-loop
      dependent nicking, base excision repair resulted in repeat instability. These
      results have implications for human repeat expansion diseases and provide a
      paradigm for how RNA:DNA hybrids can cause genome instability at structure
      forming DNA sequences. This perspective summarizes mechanisms of R-loop-induced
      fragility at G-rich repeats and new links between DNA breaks and repeat
      instability.

PMID- 29327078
TI  - The role of the thioredoxin/thioredoxin reductase system in the metabolic
      syndrome: towards a possible prognostic marker?
AB  - Mammalian thioredoxin reductase (TrxR) is a selenoprotein with three existing
      isoenzymes (TrxR1, TrxR2, and TrxR3), which is found primarily intracellularly
      but also in extracellular fluids. The main substrate thioredoxin (Trx) is
      similarly found (as Trx1 and Trx2) in various intracellular compartments, in
      blood plasma, and is the cell's major disulfide reductase. Thioredoxin reductase
      is necessary as a NADPH-dependent reducing agent in biochemical reactions
      involving Trx. Genetic and environmental factors like selenium status influence
      the activity of TrxR. Research shows that the Trx/TrxR system plays a significant
      role in the physiology of the adipose tissue, in carbohydrate metabolism, insulin
      production and sensitivity, blood pressure regulation, inflammation, chemotactic
      activity of macrophages, and atherogenesis. Based on recent research, it has been
      reported that the modulation of the Trx/TrxR system may be considered as a new
      target in the management of the metabolic syndrome, insulin resistance, and type
      2 diabetes, as well as in the treatment of hypertension and atherosclerosis. In
      this review evidence about a possible role of this system as a marker of the
      metabolic syndrome is reported.

PMID- 29327084
TI  - BACE1 inhibition more effectively suppresses initiation than progression of beta
      amyloid pathology.
AB  - BACE1 is the rate-limiting protease in the production of synaptotoxic beta
      amyloid (Abeta) species and hence one of the prime drug targets for potential
      therapy of Alzheimer's disease (AD). However, so far pharmacological BACE1
      inhibition failed to rescue the cognitive decline in mild-to-moderate AD
      patients, which indicates that treatment at the symptomatic stage might be too
      late. In the current study, chronic in vivo two-photon microscopy was performed
      in a transgenic AD model to monitor the impact of pharmacological BACE1
      inhibition on early beta-amyloid pathology. The longitudinal approach allowed to
      assess the kinetics of individual plaques and associated presynaptic pathology,
      before and throughout treatment. BACE1 inhibition could not halt but slow down
      progressive beta-amyloid deposition and associated synaptic pathology. Notably,
      the data revealed that the initial process of plaque formation, rather than the
      subsequent phase of gradual plaque growth, is most sensitive to BACE1 inhibition.
      This finding of particular susceptibility of plaque formation has profound
      implications to achieve optimal therapeutic efficacy for the prospective
      treatment of AD.

PMID- 29327085
TI  - Acceptance and commitment therapy for symptom interference in metastatic breast
      cancer patients: a pilot randomized trial.
AB  - PURPOSE: Breast cancer is the leading cause of cancer mortality in women
      worldwide. With medical advances, metastatic breast cancer (MBC) patients often
      live for years with many symptoms that interfere with activities. However, there
      is a paucity of efficacious interventions to address symptom-related suffering
      and functional interference. Thus, this study examined the feasibility and
      preliminary efficacy of telephone-based acceptance and commitment therapy (ACT)
      for symptom interference with functioning in MBC patients. METHODS: Symptomatic
      MBC patients (N = 47) were randomly assigned to six telephone sessions of ACT or
      six telephone sessions of education/support. Patients completed measures of
      symptom interference and measures assessing the severity of pain, fatigue, sleep
      disturbance, depressive symptoms, and anxiety. RESULTS: The eligibility screening
      rate (64%) and high retention (83% at 8 weeks post-baseline) demonstrated
      feasibility. When examining within-group change, ACT participants showed
      decreases in symptom interference (i.e., fatigue interference and sleep-related
      impairment; Cohen's d range = - 0.23 to - 0.31) at 8 and 12 weeks post-baseline,
      whereas education/support participants showed minimal change in these outcomes (d
      range = - 0.03 to 0.07). Additionally, at 12 weeks post-baseline, ACT
      participants showed moderate decreases in fatigue and sleep disturbance (both ds
      = - 0.43), whereas education/support participants showed small decreases in these
      outcomes (ds = - 0.24 and - 0.18 for fatigue and sleep disturbance,
      respectively). Both the ACT and education/support groups showed reductions in
      depressive symptoms (ds = - 0.27 and - 0.28) at 12 weeks post-baseline. Group
      differences in all outcomes were not statistically significant. CONCLUSIONS: ACT
      shows feasibility and promise in improving fatigue and sleep-related outcomes in
      MBC patients and warrants further investigation.

PMID- 29327086
TI  - Frequency of cerebral infarction after pulmonary resection: a multicenter,
      retrospective study in Japan.

PMID- 29327087
TI  - Use of Portable Digital Devices to Analyze Autonomic Stress Response in
      Psychology Objective Structured Clinical Examination.
AB  - The aim of the present study was to explore changes in the autonomic stress
      response of Psychology students in a Psychology Objective Structured Clinical
      Examination (OSCE) and their relationship with OSCE performance. Variables of
      autonomic modulation by the analysis of heart rate variability in temporal,
      frequency and non-linear domains, subjective perception of distress strait and
      academic performance were measured before and after the two different evaluations
      that composed the OSCE. A psychology objective structured clinical examination
      composed by two different evaluation scenarios produced a large anxiety
      anticipatory response, a habituation response in the first of the evaluation
      scenarios and a in the entire evaluation, and a no habituation response in the
      second evaluation scenario. Autonomic modulation parameters do not correlate with
      academic performance of students.

PMID- 29327088
TI  - Amplification of pressure waves in laser-assisted endodontics with synchronized
      delivery of Er:YAG laser pulses.
AB  - When attempting to clean surfaces of dental root canals with laser-induced
      cavitation bubbles, the resulting cavitation oscillations are significantly
      prolonged due to friction on the cavity walls and other factors. Consequently,
      the collapses are less intense and the shock waves that are usually emitted
      following a bubble's collapse are diminished or not present at all. A new
      technique of synchronized laser-pulse delivery intended to enhance the emission
      of shock waves from collapsed bubbles in fluid-filled endodontic canals is
      reported. A laser beam deflection probe, a high-speed camera, and shadow
      photography were used to characterize the induced photoacoustic phenomena during
      synchronized delivery of Er:YAG laser pulses in a confined volume of water. A
      shock wave enhancing technique was employed which consists of delivering a second
      laser pulse at a delay with regard to the first cavitation bubble-forming laser
      pulse. Influence of the delay between the first and second laser pulses on the
      generation of pressure and shock waves during the first bubble's collapse was
      measured for different laser pulse energies and cavity volumes. Results show that
      the optimal delay between the two laser pulses is strongly correlated with the
      cavitation bubble's oscillation period. Under optimal synchronization conditions,
      the growth of the second cavitation bubble was observed to accelerate the
      collapse of the first cavitation bubble, leading to a violent collapse, during
      which shock waves are emitted. Additionally, shock waves created by the
      accelerated collapse of the primary cavitation bubble and as well of the
      accompanying smaller secondary bubbles near the cavity walls were observed. The
      reported phenomena may have applications in improved laser cleaning of surfaces
      during laser-assisted dental root canal treatments.

PMID- 29327089
TI  - Comparative efficacy of Er,Cr:YSGG and Er:YAG lasers for etching of composite for
      orthodontic bracket bonding.
AB  - Several techniques have been proposed to obtain a durable bond, and the efficacy
      of these techniques is assessed by measuring parameters such as bond strength.
      Laser has provided a bond strength as high as that of acid etching in vitro and
      has simpler use with shorter clinical time compared to acid etching. This study
      aimed to compare the efficacy of Er:YAG and Er,Cr:YSGG lasers for etching and
      bonding of composite to orthodontic brackets. No previous study has evaluated the
      effect of these particular types of laser. A total of 70 composite blocks were
      randomly divided into five groups (n = 14): group 1, etching with phosphoric acid
      for 20 s; group 2, Er:YAG laser irradiation with 2 W power for 10 s; group 3,
      Er:YAG laser with 3 W power for 10 s; group 4, Er,Cr:YSGG laser with 2 W power
      for 10 s; group 5, Er,Cr:YSGG laser with 3 W power for 10 s. Metal brackets were
      then bonded to composites, and after 5000 thermal cycles, they were subjected to
      shear bond strength test in a universal testing machine after 24 h of water
      storage. One sample of each group was evaluated under a scanning electron
      microscope (SEM) to assess changes in composite surface after etching. The
      adhesive remnant index (ARI) was calculated under a stereomicroscope. Data were
      statistically analyzed. The mean and standard deviation of shear bond strength
      were 18.65 +/- 3.36, 19.68 +/- 5.34, 21.31 +/- 4.03, 17.38 +/- 6.94, and 16.45 +/
      4.26 MPa in groups 1-5, respectively. The ARI scores showed that the bond
      failure mode in all groups was mainly mixed. The groups were not significantly
      different in terms of shear bond strength. Er:YAG and Er,Cr:YSGG lasers with the
      mentioned parameters yield optimal shear bond strength and can be used as an
      alternative to acid etching for bracket bond to composite.

PMID- 29327090
TI  - Alcohol Use and Unprotected Sex Among HIV-Infected Ugandan Adults: Findings from
      an Event-Level Study.
AB  - While alcohol is a known risk factor for HIV infection in sub-Saharan Africa
      (SSA), studies designed to investigate the temporal relationship between alcohol
      use and unprotected sex are lacking. The purpose of this study was to determine
      whether alcohol used at the time of a sexual event is associated with unprotected
      sex at that same event. Data for this study were collected as part of two
      longitudinal studies of HIV-infected Ugandan adults. A structured questionnaire
      was administered at regularly scheduled cohort study visits in order to assess
      the circumstances (e.g., alcohol use, partner type) of the most recent sexual
      event (MRSE). Generalized estimating equation logistic regression models were
      used to examine the association between alcohol use (by the participant, the
      sexual partner, or both the participant and the partner) and the odds of
      unprotected sex at the sexual event while controlling for participant gender,
      age, months since HIV diagnosis, unhealthy alcohol use in the prior 3 months,
      partner type, and HIV status of partner. A total of 627 sexually active
      participants (57% women) reported 1817 sexual events. Of these events, 19%
      involved alcohol use and 53% were unprotected. Alcohol use by one's sexual
      partner (aOR 1.70; 95% CI 1.14, 2.54) or by both partners (aOR 1.78; 95% CI 1.07,
      2.98) during the MRSE significantly increased the odds of unprotected sex at that
      same event. These results add to the growing event-level literature in SSA and
      support a temporal association between alcohol used prior to a sexual event and
      subsequent unprotected sex.

PMID- 29327091
TI  - Temporal Fluctuations in Behavior, Perceived HIV Risk, and Willingness to Use Pre
      Exposure Prophylaxis (PrEP).
AB  - Individual perceptions of HIV risk influence willingness to use pre-exposure
      prophylaxis (PrEP) for HIV prevention. Among men who have sex with men (MSM) and
      male sex workers (MSWs), temporal or episodic changes in risk behavior may
      influence perceived risk and PrEP acceptability over time. We investigated
      fluctuations in perceived HIV risk and PrEP acceptability, comparing MSWs against
      MSM who do not engage in sex work. We conducted 8 focus groups (n = 38) and 56
      individual interviews among MSM and MSWs in Providence, RI. Perceived HIV risk
      shaped willingness to use PrEP among both MSWs and MSM who did not engage in sex
      work, and risk perceptions changed over time depending on behavior. For MSWs,
      perceived risk cycled according to patterns of substance use and sex work
      activity. These cycles yielded an "access-interest paradox": an inverse
      relationship between willingness to use and ability to access PrEP. MSM who did
      not engage in sex work also reported temporal shifts in risk behavior, perceived
      risk, and willingness to use PrEP, but changes were unrelated to access. MSM
      attributed fluctuations to seasonal changes, vacations, partnerships, behavioral
      "phases," and episodic alcohol or drug use. Efforts to implement PrEP among MSM
      and street-based MSWs should address temporal changes in willingness to use PrEP,
      which are linked to perceived risk. Among MSWs, confronting the access-interest
      paradox may require intensive outreach during high-risk times and efforts to
      address low perceived risk during times of reduced sex work.

PMID- 29327092
TI  - Mesoporous Nickel Oxide (NiO) Nanopetals for Ultrasensitive Glucose Sensing.
AB  - Glucose sensing properties of mesoporous well-aligned, dense nickel oxide (NiO)
      nanostructures (NSs) in nanopetals (NPs) shape grown hydrothermally on the FTO
      coated glass substrate has been demonstrated. The structural study based
      investigations of NiO-NPs has been carried out by X-ray diffraction (XRD),
      electron and atomic force microscopies, energy dispersive X-ray (EDX), and X-ray
      photospectroscopy (XPS). Brunauer-Emmett-Teller (BET) measurements, employed for
      surface analysis, suggest NiO's suitability for surface activity based glucose
      sensing applications. The glucose sensor, which immobilized glucose on NiO
      NPs@FTO electrode, shows detection of wide range of glucose concentrations with
      good linearity and high sensitivity of 3.9 MUA/MUM/cm2 at 0.5 V operating
      potential. Detection limit of as low as 1 MUMU and a fast response time of less
      than 1 s was observed. The glucose sensor electrode possesses good anti
      interference ability, stability, repeatability & reproducibility and shows inert
      behavior toward ascorbic acid (AA), uric acid (UA) and dopamine acid (DA) making
      it a perfect non-enzymatic glucose sensor.

PMID- 29327093
TI  - MiR-181 family-specific behavior in different cancers: a meta-analysis view.
AB  - The involvement of microRNAs in malignant transformation and cancer progression
      was previously grounded. The observations made by multiple published studies led
      to the conclusion that some of these small sequences could be eventually used as
      biomarkers for diagnosis/prognosis. This meta-analysis investigated whether
      microRNA-181 family members could predict the outcome of patients carrying
      different types of cancer. We searched the PubMed and Embase databases for
      studies evaluating the expression levels of miR-181a/b/c/d in patients with
      cancer, selecting the publications that assessed the relation between low and
      high levels of one of these four microRNAs and patients' outcome. Hazard ratios
      (HRs) or risk ratios (RRs) were extracted from the studies, and random-effect
      model was performed to investigate the role of miR-181 in the outcome of these
      patients. The meta-analysis comprised 26 studies including 2653 cancer patients
      from 6 countries. The results showed significant association between the
      expression of miR-181 family members and colorectal cancer. Considering the
      heterogeneity of the pathologies, the analysis, including all types of cancer and
      the expression of all the miR-181 family members together, showed no association
      with distinct outcome (HR = 1.099, p = 0.435). When the analysis was performed on
      each microRNA separately, the expression of miR-181c was significantly associated
      with the outcome of patients with cancer (HR = 2.356, p = 0.011) and miR-181a
      expression levels significantly correlated with survival in patients with non
      small-cell lung cancer (HR = 0.177, p < 0.05). This meta-analysis revealed
      evidence regarding the involvement of miR-181 family members in the outcome of
      patients with some types of cancer, according to their expression level.

PMID- 29327094
TI  - Association between secondhand smoke exposure and quality of life in pregnant
      women and postpartum women and the consequences on the newborns.
AB  - PURPOSE: Secondhand smoke (SHS) exposure is prevalent and could damage the health
      of non-smokers, especially that of pregnant women (PW) and postpartum women
      (PPW). Nevertheless, there is no study on the impact of SHS during pregnancy on
      the quality of life (QOL) of PW and PPW. The study's purpose is to study the
      effects of exposure to SHS on the QOL of pregnant and postpartum women and health
      of the newborns. METHODS: Self-reports and urine tests for cotinine were used to
      obtain data on SSH exposure in 296 women in the second trimester of pregnancy and
      106 women in the postpartum period at the Obstetrics & Gynecology Clinic located
      in a university hospital. The WHOQOL-BREF-THAI and the Edinburgh Postnatal
      Depression Scale were used to assess QOL and postpartum depression, respectively.
      RESULTS: Of the participants, 88.2% of PW and 62.3% of PPW reported exposure to
      SHS during pregnancy. Of the PPW, 5.7% had postpartum depression. PW with good
      QOL were less likely to have family member who smoked (p = 0.007) or to be
      exposed to SHS in public parks (p = 0.037) or in the household or workplace (p =
      0.011). Likewise, PPW with good QOL in the psychological domain were less likely
      to be exposed to SHS during pregnancy, as shown in both verbal report (p = 0.010)
      and objective measure of urine cotinine test (p = 0.034). In addition, maternal
      exposure to SHS during pregnancy is associated with low birth weight and other
      health problems in the newborns (p < 0.05). CONCLUSIONS: Exposure to SHS during
      pregnancy is associated with a lower QOL and a poorer health condition in the
      newborns.

PMID- 29327095
TI  - Longitudinal Links Between Gambling Participation and Academic Performance in
      Youth: A Test of Four Models.
AB  - Gambling participation and low academic performance are related during
      adolescence, but the causal mechanisms underlying this link are unclear. It is
      possible that gambling participation impairs academic performance. Alternatively,
      the link between gambling participation and low academic performance could be
      explained by common underlying risk factors such as impulsivity and socio-family
      adversity. It could also be explained by other current correlated problem
      behaviors such as substance use. The goal of the present study was to examine
      whether concurrent and longitudinal links between gambling participation and low
      academic performance exist from age 14 to age 17 years, net of common antecedent
      factors and current substance use. A convenience sample of 766 adolescents (50.6%
      males) from a longitudinal twin sample participated in the study. Analyses
      revealed significant, albeit modest, concurrent links at both ages between
      gambling participation and academic performance. There was also a longitudinal
      link between gambling participation at age 14 and academic performance at age 17,
      which persisted after controlling for age 12 impulsivity and socio-family
      adversity as well as current substance use. Gambling participation predicts a
      decrease in academic performance during adolescence, net of concurrent and
      antecedent personal and familial risk factors.

PMID- 29327096
TI  - [Focused ultrasound ablation as tremor treatment].
AB  - BACKGROUND: The development of high-intensity magnetic resonance imaging (MRI)
      guided focused ultrasound (MRIgFUS) ablation has widened the spectrum of
      interventional techniques for stereotactic functional neurosurgery of lesions.
      This has resulted in novel incisionless intervention approaches for the therapy
      of tremor disorders. The safety and efficacy is documented by recent study data.
      OBJECTIVES: This article encompasses a description of the technological basis and
      typical course of MRIgFUS interventions, a comparison to alternative open or
      incisionless surgical techniques as well as a review of the current evidence base
      for MRIgFUS ablation in the context of lesional interventions to treat tremor.
      MATERIAL AND METHODS: Narrative literature review and comparison. RESULTS:
      Depending on the surgical target and tremor etiology published trials of MRIgFUS
      ablation report a reduction of tremor intensity of up to 80% after 6-12 months
      follow-up without the disadvantages of open brain surgery. CONCLUSION: The
      MRIgFUS functional neurosurgery is conducted only at a limited number of
      treatment sites. First data on lesions of the thalamic ventral intermediary
      nucleus (V.im.) as well as subthalamic fiber tracts have been published. These
      results indicate an effective and safe treatment of tremor disorders by MRIgFUS
      ablation. Incisionless lesional surgery using MRIgFUS is a significant addition
      to the interventional armamentarium for functional stereotactic neurosurgery and
      a potentially valuable alternative to established interventional therapy options
      for tremor disorders.

PMID- 29327097
TI  - [Clinical and cognitive aspects of functional (psychogenic) tremor].
AB  - Functional (psychogenic) tremor is the most common functional movement disorder.
      Characteristic clinical features, so called red flags, can help to make the
      clinical distinction of this type from other tremor disorders. The most common
      features include the variability of frequency and amplitude. Clinical examination
      should include different types of distraction including motor or cognitive tasks
      or testing the influence of suggestibility on tremor amplitude, frequency or
      direction. Patients often report sudden onset and remissions that may last for
      months or even years. In some cases, the tremor is only present in highly
      specific situations. Although functional tremor shares characteristics with
      voluntary actions, patients experience their abnormal movements as involuntary.
      Recent experimental approaches have revealed an impairment in sense of agency.
      The diagnosis can be supported by neurophysiological measurements including
      accelerometry, which achieved a sensitivity of 89.5% and a specificity of 95.9%
      in a validated test battery, thus providing a useful additional diagnostic tool.
      Psychotherapeutic treatment is indicated in patients with and without evident
      psychological symptoms. A specific physiotherapeutic approach for functional
      tremor is re-trainment.

PMID- 29327098
TI  - [Rare tremor syndromes].
AB  - BACKGROUND: There is a group of uncommon sporadic tremor syndromes, which are
      only partially taken into account in the current classification of tremor. Their
      knowledge is of diagnostic and therapeutic relevance and they should be
      considered in the differential diagnosis of frequent tremor syndromes. OBJECTIVE:
      Differential diagnostics and treatment of uncommon tremor syndromes. METHOD:
      Literature search (PubMed, Google Scholar). RESULTS: Holmes tremor, myorhythmia,
      palatal tremor, limb-shaking transient ischemic attack (TIA), tardive tremor,
      neuropathic tremor, tremor induced by peripheral trauma and orthostatic tremor
      syndrome are described. CONCLUSION: Uncommon sporadic tremor syndromes are mainly
      symptomatic with various underlying neurological or systemic pathologies. Their
      recognition accelerates the diagnostic process and has therapeutic relevance.

PMID- 29327099
TI  - [Genetics of tremor].
AB  - BACKGROUND: Tremor is a symptom of many diseases and can constitute a disease of
      its own: essential tremor. OBJECTIVE: The genetics of essential tremor and
      differential diagnosis of monogenic diseases with the symptom tremor. MATERIAL
      AND METHODS: Literature search and search of clinical genetics databases, e.g.
      OMIM, GeneReviews, MDSGene and the German Neurological Society (DGN) guidelines.
      RESULTS: The genetics of essential tremor remain unresolved in spite of large,
      adequately powered studies. Tremor is a symptom of differential diagnostic value
      in many movement disorders. A slight tremor might have been missed or not
      reported in many descriptions of movement disorders. CONCLUSION: Progress in the
      genetics of essential tremor probably requires a more detailed phenotyping
      allowing stratification into phenotypically defined subgroups. Tremor should
      always be included in the examination and description of movement disorders even
      if tremor is not a cardinal symptom. Tremor might be helpful in the differential
      diagnosis of hereditary dystonia, hereditary ataxia, spastic paraplegia and other
      movement disorders.

PMID- 29327100
TI  - [Provision of palliative care for people with advanced dementia].
AB  - As a result of a literature-based expert process, this review provides an
      overview about the principles of palliative care for people with advanced
      dementia that are relevant for clinical practice. In particular, the indications,
      impact and aims of palliative care for advanced dementia are described. Life
      prolonging measures and management of symptoms at the end of life are discussed.
      Furthermore, the overview focuses on the legal basis of decision making.

PMID- 29327102
TI  - Chemical shift assignments of retinal degeneration 3 protein (RD3).
AB  - Retinal degeneration 3 protein (RD3) binds to retinal membrane guanylyl cyclase
      (RetGC) and suppresses the basal activity of RetGC in photoreceptor cells that
      opposes the allosteric activation of the cyclase by GCAP proteins. Mutations in
      RD3 that disrupt its inhibition of RetGC are implicated in human retinal
      degenerative disorders. Here we report both backbone and sidechain NMR
      assignments for the RD3 protein (BMRB accession no. 27305).

PMID- 29327103
TI  - 1H, 13C and 15N resonance assignments of NEDD8 from Trypanosoma brucei.
AB  - Neural precursor cell-expressed, developmently downregulated 8 (NEDD8) is a small
      ubiquitin-like modifier, which plays important roles in many cellular processes.
      Although it has been well studied in many eukaryotes, NEDD8 is still
      uncharacterized in some unicellular parasites, such as Trypanosoma brucei (T.
      brucei). Here we report the resonance assignments of NEDD8 from T. brucei.

PMID- 29327104
TI  - Long-term efficacy of spa therapy in patients with rheumatoid arthritis.
AB  - Our previous crossover randomized trial suggested that spa therapy added to usual
      pharmacotherapy provides benefits that lasted 6 months over pharmacotherapy alone
      in rheumatoid arthritis patients. We now extend, and report the long-term results
      of that study. In the crossover trial, patients were randomized to spa therapy
      first group or control first group (first assignment, period 1, 6 months); after
      this period and washout phase (9 months), they crossed over to the other arm
      (second assignment, period 2, 6 months). In this long-term study, we now analyze
      the 15-month results of the first assignment, and 12-month results of the second
      assignment in the opposite side with a 6-month extension of the follow-up period.
      The clinical outcome measures were pain, patient and physician global assessment,
      Health Assessment Questionnaire, and Disease Activity Score-28. The 15-month
      results of first assignment revealed no statistically significant differences
      between the groups in any of the efficacy outcomes (p > 0.05 for all). The 12
      month results for the second assignment after crossover revealed a statistically
      significant decrease between the groups regarding the patient global assessment
      scores (p = 0.016), physician global assessment scores (p = 0.003) and swollen
      joints counts (p = 0.030); however, no statistically significant difference was
      found between the groups in any of the other efficacy outcomes (p > 0.05 for
      all). The short- and medium-term beneficial effects of the 2-week spa therapy
      added to the usual pharmacotherapy observed through the initial 6-month
      evaluation period may be maintained mildly to moderately to the 12-month mark in
      rheumatoid arthritis patients receiving conventional disease-modifying
      antirheumatic drugs. Further studies with a larger sample size are needed for the
      confirmation of the study results.

PMID- 29327105
TI  - Catalytic Effect of Pd Clusters in the Poly(N-vinyl-2-pyrrolidone) Combustion.
AB  - Pd(0) is able to catalyze oxygen-involving reactions because of its capability to
      convert molecular oxygen to the very reactive atomic form. Consequently, the
      embedding of a little amount of Pd(0) clusters in polymeric phases can be
      technologically exploited to enhance the incineration kinetic of these polymers.
      The effect of nanostructuration on the Pd(0) catalytic activity in the polymer
      incineration reaction has been studied using poly(N-vinyl-2-pyrrolidone)
      ([Formula: see text] = 10,000 gmol-1) as polymeric model system. A change in the
      PVP incineration kinetic mechanism with significant increase in the reaction rate
      was experimentally found. The kinetic of the Pd(0)-catalyzed combustion has been
      studied by isothermal thermogravimetric analysis. After a short induction time,
      the combustion in presence of Pd(0) clusters shifted to a zero-order kinetic from
      a second-order kinetic control, which is operative in pure PVP combustion
      reaction. In addition, the activation energy resulted much lowered compared to
      the pure PVP incineration case (from 300 to 260 kJ/mol).

PMID- 29327101
TI  - Fundamentals of siRNA and miRNA therapeutics and a review of targeted
      nanoparticle delivery systems in breast cancer.
AB  - Gene silencing via RNA interference (RNAi) is rapidly evolving as a personalized
      approach to cancer treatment. The effector molecules-small interfering RNAs
      (siRNAs) and microRNAs (miRNAs)-can be used to silence or "switch off" specific
      cancer genes. Currently, the main barrier to implementing siRNA- and miRNA-based
      therapies in clinical practice is the lack of an effective delivery system that
      can protect the RNA molecules from nuclease degradation, deliver to them to tumor
      tissue, and release them into the cytoplasm of the target cancer cells, all
      without inducing adverse effects. Here, we review the fundamentals of RNAi, cell
      membrane transport pathways, and factors that affect intracellular delivery. We
      discuss the advantages and disadvantages of the various types of nanoparticle
      delivery systems, with a focus on those that have been investigated in breast
      cancer in vivo.

PMID- 29327106
TI  - MDCT of ductus diverticulum: 3D cinematic rendering to enhance understanding of
      anatomic configuration and avoid misinterpretation as traumatic aortic injury.
AB  - Acute aortic injuries are not common in the setting of severe blunt trauma, but
      lead to significant morbidity and mortality. High-quality MDCT with 2D MPRs and
      3D rendering are essential to identify aortic trauma and distinguish anatomic
      variants and other forms of aortic pathology from an acute injury.
      Misinterpretation of mimics of acute aortic injury can lead to unnecessary
      arteriography and thoracic surgery. Since most traumatic injuries occur in the
      distal arch, radiologists must be cognizant of the range of appearances of
      variants related to the ductus diverticulum. Cinematic rendering (CR) is a new 3D
      post-processing tool that provides even greater anatomic detail than traditional
      volume rendering. In this case series, CR is used to impart to radiologists a
      better understanding of various anatomic configurations that can be seen with a
      ductus diverticulum.

PMID- 29327107
TI  - Imaging of pediatric neurovascular emergencies.
AB  - Pediatric strokes are rare but critical diagnoses to make in the emergency
      setting. They are associated with a set of pathologies that are not frequently
      encountered in the adult population. Some of these diseases have variable
      clinical presentations and imaging appearance depending on the age of onset and
      severity of the underlying pathologies. This article reviews the differential
      diagnoses and noninvasive imaging evaluation of pediatric cerebral ischemic and
      hemorrhagic diseases.

PMID- 29327108
TI  - Computed tomography for occult fractures of the proximal femur, pelvis, and
      sacrum in clinical practice: single institution, dual-site experience.
AB  - PURPOSE: The purpose of this study was to evaluate the diagnostic performance of
      CT for assessment of occult fractures of the proximal femur, pelvis, and sacrum.
      MATERIALS AND METHODS: A retrospective review was performed on patients who
      received a CT of the hip or pelvis for suspected occult fracture after negative
      or equivocal radiographs performed within 24 h. The official radiology report was
      utilized for the determination of CT findings and calculation of sensitivity and
      specificity. Surgical reports, MRI reports, and clinical follow-up were used as
      the standard of reference. Sensitivity and specificity were calculated with 95%
      confidence intervals. RESULTS: Seventy-four patients received CT of the hip or
      pelvis for clinical concern for occult fracture after negative or equivocal
      radiographs. By the reference standard, a total of 40 fractures were present in
      25/74 (33.8%) patients, including 35 conservatively treated fractures of the
      greater trochanter, pelvis, and sacrum, and 5 operatively treated proximal
      femoral fractures. A total of 14/74 (18.9%) of patients had an MRI within 1 day
      of CT. MRI identified an operatively treated femoral neck fracture not seen on CT
      and an operatively treated intertrochanteric fracture, which CT described as a
      greater trochanteric fracture. There were two false negative conservatively
      treated pelvic fractures not seen on CT but diagnosed on MRI. On a per-patient
      basis, CT had an overall sensitivity of 88% (22/25; 95% confidence intervals 69
      97%), specificity of 98% (48/49; 95% confidence intervals 89-100%), and negative
      predictive value of 94%. For the five operative proximal femoral fractures, the
      sensitivity of CT was 60% (3/5; 95% confidence intervals 15-95%), specificity was
      99% (68/69; 95% confidence intervals 92-100%), and negative predictive value was
      97%. CONCLUSIONS: In the clinical setting of suspected occult fracture, the
      sensitivity of clinical CT reports for detection of any type of fracture of the
      proximal femur, pelvis, or sacrum was 88%. For the small number of operatively
      treated proximal femoral fractures seen in the study, sensitivity of CT was 60%
      (3/5) and negative predictive value was 97%, although the relatively few patients
      needing fixation precludes statistical analysis.

PMID- 29327110
TI  - The role of interleukin-2, all-trans retinoic acid, and natural killer cells:
      surveillance mechanisms in anti-GD2 antibody therapy in neuroblastoma.
AB  - Although anti-disialoganglioside (GD2) antibodies are successfully used for
      neuroblastoma therapy, a third of patients with neuroblastoma experience
      treatment failure or serious toxicity. Various strategies have been employed in
      the clinic to improve antibody-dependent cell-mediated cytotoxicity (ADCC), such
      as the addition of interleukin (IL)-2 to enhance natural killer (NK) cell
      function, adoptive transfer of allogeneic NK cells to exploit immune
      surveillance, and retinoid-induced differentiation therapy. Nevertheless, these
      mechanisms are not fully understood. We developed a quantitative assay to test
      ADCC induced by the anti-GD2 antibody Hu14.18K322A in nine neuroblastoma cell
      lines and dissociated cells from orthotopic patient-derived xenografts (O-PDXs)
      in culture. IL-2 improved ADCC against neuroblastoma cells, and differentiation
      with all-trans retinoic acid stabilized GD2 expression on tumor cells and
      enhanced ADCC as well. Degranulation was highest in licensed NK cells that
      expressed CD158b (P < 0.001) and harbored a killer-cell immunoglobulin-like
      receptor (KIR) mismatch against the tumor-specific human leukocyte antigen (HLA;
      P = 0.016). In conclusion, IL-2 is an important component of immunotherapy
      because it can improve the cytolytic function of NK cells against neuroblastoma
      cells and could lower the antibody dose required for efficacy, thereby reducing
      toxicity. The effect of IL-2 may vary among individuals and a biomarker would be
      useful to predict ADCC following IL-2 activation. Sub-populations of NK cells may
      have different levels of activity dependent on their licensing status, KIR
      expression, and HLA-KIR interaction. Better understanding of HLA-KIR interactions
      and the molecular changes following retinoid-induced differentiation is necessary
      to delineate their role in ADCC.

PMID- 29327111
TI  - The role of the endometrial receptivity array (ERA) in patients who have failed
      euploid embryo transfers.
AB  - PURPOSE: Endometrial receptivity issues represent a potential source of
      implantation failure. The aim of this study was to document our experience with
      the endometrial receptivity array (ERA) among patients with a history of euploid
      blastocyst implantation failure. We investigated whether the contribution of the
      endometrial factor could be identified with the ERA test and if actionable
      results can lead to improved outcomes. METHODS: A retrospective review was
      performed for 88 patients who underwent ERA testing between 2014 and 2017.
      Reproductive outcomes were compared for patients undergoing frozen embryo
      transfer (FET) using a standard progesterone protocol versus those with non
      receptive results by ERA and subsequent FET according to a personalized embryo
      transfer (pET) protocol. RESULTS: Of patients with at least one previously failed
      euploid FET, 22.5% had a displaced WOI diagnosed by ERA and qualified for pET.
      After pET, we found that implantation and ongoing pregnancy rates were higher
      (73.7 vs. 54.2% and 63.2 vs. 41.7%, respectively) compared to patients without
      pET, although differences were not statistically significant. CONCLUSIONS: Our
      experience demonstrates that a significant proportion of patients with a history
      of implantation failure of a euploid embryo have a displaced WOI as detected by
      the ERA. For these patients, pET using a modified progesterone protocol may
      improve the outcomes of subsequent euploid FET. Larger randomized studies are
      required to validate these results.

PMID- 29327109
TI  - A novel biologic platform elicits profound T cell costimulatory activity and
      antitumor immunity in mice.
AB  - Combination immunotherapies utilizing complementary modalities that target
      distinct tumor attributes or immunosuppressive mechanisms, or engage different
      arms of the antitumor immune response, can elicit greater therapeutic efficacy
      than the component monotherapies. Increasing the number of agents included in a
      therapeutic cocktail can further increase efficacy, however, this approach poses
      numerous challenges for clinical translation. Here, a novel platform to simplify
      combination immunotherapy by covalently linking immunotherapeutic agonists to the
      costimulatory receptors CD134 and CD137 into a single heterodimeric drug,
      "OrthomAb", is shown. This reagent not only retains costimulatory T cell
      activity, but also elicits unique T cell functions that are not programmed by
      either individual agonist, and preferentially expands effector T cells over
      Tregs. Finally, in an aggressive melanoma model OrthomAb elicits better
      therapeutic efficacy compared to the unlinked agonists. This demonstration that
      two drugs can be combined into one provides a framework for distilling complex
      combination drug cocktails into simpler delivery platforms.

PMID- 29327112
TI  - Simultaneous pre-concentration and separation on simple paper-based analytical
      device for protein analysis.
AB  - In this work, fast isoelectric focusing (IEF) was successfully implemented on an
      open paper fluidic channel for simultaneous concentration and separation of
      proteins from complex matrix. With this simple device, IEF can be finished in 10
      min with a resolution of 0.03 pH units and concentration factor of 10, as
      estimated by color model proteins by smartphone-based colorimetric detection.
      Fast detection of albumin from human serum and glycated hemoglobin (HBA1c) from
      blood cell was demonstrated. In addition, off-line identification of the model
      proteins from the IEF fractions with matrix-assisted laser desorption ionization
      time-of-flight mass spectrometry (MALDI-TOF-MS) was also shown. This PAD IEF is
      potentially useful either for point of care test (POCT) or biomarker analysis as
      a cost-effective sample pretreatment method.

PMID- 29327113
TI  - Storage stability study of porcine hepatic and intestinal cytochrome P450
      isoenzymes by use of a newly developed and fully validated highly sensitive HPLC
      MS/MS method.
AB  - Microsomes are an ideal medium to investigate cytochrome P450 (CYP450) enzyme
      mediated drug metabolism. However, before microsomes are prepared, tissues can be
      stored for a long time. Studies about the stability of these enzymes in porcine
      hepatic and intestinal tissues upon storage are lacking. To be able to
      investigate CYP450 stability in microsomes prepared from these tissues, a highly
      sensitive and rapid HPLC-MS/MS method for the simultaneous determination of six
      CYP450 metabolites in incubation medium was developed and validated. The
      metabolites, paracetamol (CYP1A), 7-hydroxy-coumarin (CYP2A), 1-hydroxy-midazolam
      (CYP3A), 4-hydroxy-tolbutamide (CYP2C), dextrorphan (CYP2D), and 6-hydroxy
      chlorzoxazone (CYP2E) were extracted with ethyl acetate at pH 1.0, followed by
      evaporation and separation on an Agilent Zorbax Eclipse Plus C18 column. The
      method was fully validated in a GLP-compliant laboratory according to European
      guidelines and was highly sensitive (LOQ = 0.25-2.5 ng/mL), selective, had good
      precision (RSD-within, 1.0-9.1%; RSD-between, 1.0-18.4%) and accuracy (within
      run, 83.3-102%; between-run, 78.5-102%), and showed no relative signal
      suppression and enhancement. Consequently, this method was applied to study the
      stability of porcine hepatic and intestinal CYP450 isoenzymes when tissues were
      stored at - 80  degrees C. The results indicate that porcine CYP450 isoenzymes
      are stable in tissues at least up to 4 months when snap frozen and stored at - 80
      degrees C. Moreover, the results indicate differences in porcine CYP450
      stability compared to rat, rabbit, and fish CYP450, as observed by other research
      groups, hence stressing the importance to investigate the CYP450 stability of a
      specific species.

PMID- 29327115
TI  - Investigation of an appropriate contrast-enhanced CT protocol for young patients
      following the Fontan operation.
AB  - PURPOSE: Children with congenital heart diseases (CHDs) may need to be followed
      up with contrast-enhanced CT following the Fontan operation because complications
      such as the occlusion of conduits may occur. The purpose of the present study was
      to develop an adequate contrast-enhanced CT protocol for children with CHD
      following the Fontan operation. MATERIALS AND METHODS: Between July 2012 and July
      2017, 29 CT examinations for 26 patients aged 2-11 years (median 5 years) with
      CHD following the Fontan operation were performed using dual-source CT. A non
      ionized contrast medium was injected through the dorsum manus vein. Scanning
      began 60 or 70 s after the start of the injection. The delayed phase was randomly
      selected to be 60 s in 14 cases and 70 s in 15 cases. We evaluated the
      enhancement of conduits following the Fontan operation at delayed phases.
      RESULTS: The CT numbers of conduits at 60 and 70 s were 185 +/- 46 and 185 +/- 31
      HU, respectively (P = 0.97). CONCLUSION: In contrast-enhanced CT for children
      after the Fontan operation, both of the delayed phases (60 and 70 s) appeared to
      be adequate for evaluating intraconduit patency.

PMID- 29327114
TI  - Anthropometric characteristics and ovarian cancer risk and survival.
AB  - PURPOSE: Multiple studies have examined the role of anthropometric
      characteristics in ovarian cancer risk and survival; however, their results have
      been conflicting. We investigated the associations between weight change, height
      and height change and risk and outcome of ovarian cancer using data from a large
      population-based case-control study. METHODS: Data from 699 ovarian cancer cases
      and 1,802 controls who participated in the HOPE study were included. We used
      unconditional logistic regression adjusted for age, race, number of pregnancies,
      use of oral contraceptives, and family history of breast or ovarian cancer to
      examine the associations between self-reported height and weight and height
      change with ovarian cancer risk. Cox proportional hazards regression models
      adjusted for age and stage were used to examine the association between the
      exposure variables and overall and progression-free survival among ovarian cancer
      cases. RESULTS: We observed an increased risk of ovarian cancer mortality and
      progression for gaining more than 20 pounds between ages 18-30, HR 1.36; 95% CI
      1.05-1.76, and HR 1.31; 95% CI 1.04-1.66, respectively. Losing weight and gaining
      it back multiple times was inversely associated with both ovarian cancer risk, OR
      0.78; 95% CI 0.63-0.97 for 1-4 times and OR 0.73; 95% CI 0.54-0.99 for 5-9 times,
      and mortality, HR 0.63; 95% CI 0.40-0.99 for 10-14 times. Finally, being taller
      during adolescence and adulthood was associated with increased risk of mortality.
      Taller stature and weight gain over lifetime were not related to ovarian cancer
      risk. CONCLUSIONS: Our results suggest that height and weight and their change
      over time may influence ovarian cancer risk and survival. These findings suggest
      that biological mechanisms underlying these associations may be hormone driven
      and may play an important role in relation to ovarian carcinogenesis and tumor
      progression.

PMID- 29327116
TI  - Evaluation of hemodynamic imaging findings of hypervascular hepatocellular
      carcinoma: comparison between dynamic contrast-enhanced magnetic resonance
      imaging using radial volumetric imaging breath-hold examination with k-space
      weighted image contrast reconstruction and dynamic computed tomography during
      hepatic arteriography.
AB  - PURPOSE: To compare the visualization of hemodynamic imaging findings of
      hypervascular hepatocellular carcinoma (HCC) on dynamic contrast-enhanced
      magnetic resonance imaging (DCE-MRI) using radial volumetric imaging breath-hold
      examination with k-space-weighted image contrast reconstruction (r-VIBE-KWIC)
      versus dynamic computed tomography during hepatic arteriography (dyn-CTHA).
      MATERIALS AND METHODS: We retrospectively reviewed the databases of preoperative
      DCE-MRI using r-VIBE-KWIC, dyn-CTHA, and postoperative pathology of resected
      specimens. Fourteen patients with 14 hypervascular HCCs underwent both DCE-MRI
      and dyn-CTHA. The imaging findings of the tumor and adjacent liver parenchyma
      were assessed on both modalities by two readers. The tumor enhancement time was
      also compared between the two modalities. RESULTS: On DCE-MRI/dyn-CTHA, early
      staining, peritumoral low-intensity or low-density bands, corona enhancement, and
      washout of HCC were observed in 14/14 (100%), 10/12 (83%), 11/14 (78%), and 4/14
      (29%) patients, respectively. Pathologically, four HCCs with low-density bands on
      dyn-CTHA had no fibrous capsules. The median tumor enhancement time on DCE-MRI
      and dyn-CTHA was 24 (9-24) and 23 (8-35) s, respectively. The correlation
      coefficient between the two groups was 0.762 (P < 0.002). CONCLUSIONS: DCE-MRI
      using r-VIBE-KWIC has diagnostic potential comparable with that of dyn-CTHA in
      the hemodynamic evaluation of hypervascular HCC except for the washout
      phenomenon.

PMID- 29327117
TI  - Graphical classification of DNA sequences of HLA alleles by deep learning.
AB  - Alleles of human leukocyte antigen (HLA)-A DNAs are classified and expressed
      graphically by using artificial intelligence "Deep Learning (Stacked
      autoencoder)". Nucleotide sequence data corresponding to the length of 822 bp,
      collected from the Immuno Polymorphism Database, were compressed to 2-dimensional
      representation and were plotted. Profiles of the two-dimensional plots indicate
      that the alleles can be classified as clusters are formed. The two-dimensional
      plot of HLA-A DNAs gives a clear outlook for characterizing the various alleles.

PMID- 29327119
TI  - Nocturnal hypoxemic burden is associated with epicardial fat volume in patients
      with acute myocardial infarction.
AB  - BACKGROUND: Increased epicardial fat volume (EFV) is a common feature of patients
      with sleep-disordered breathing (SDB), is considered as an established marker of
      cardiovascular risk, and is associated with adverse cardiovascular events after
      myocardial infarction (MI). METHODS: To investigate the association between
      different measures of SDB severity and EFV after acute MI, we enrolled 105
      patients with acute MI in this study. Unattended in-hospital polysomnography was
      performed to determine the number of apneas and hypopneas per hour during sleep
      (apnea-hypopnea index, AHI). To determine nocturnal hypoxemic burden, we used
      pulse oximetry and applied a novel parameter, the hypoxia load representing the
      integrated area of desaturation divided by total sleep time (HLTST). Of 105
      patients, 56 underwent cardiovascular magnetic resonance to define EFV. RESULTS:
      HLTST was significantly associated with EFV (r2 = 0.316, p = 0.025). Multivariate
      linear regression analysis accounting for age, sex, body mass index, smoking, and
      left ventricular mass demonstrated that the HLTST was an independent modulator of
      EFV (B-coefficient 0.435 (95% CI 0.021-0.591); p = 0.015). In contrast, AHI or
      established measures of hypoxemia did not correlate with EFV. CONCLUSIONS: HLTST,
      a novel parameter to determine nocturnal hypoxemic burden, and not AHI as an
      event-based measure of SDB, was associated with EFV in patients with acute MI.
      Further studies are warranted to confirm the link between nocturnal hypoxemia and
      EFV and to determine the prognostic value of a more detailed characterization of
      nocturnal hypoxemic burden in patients with high cardiovascular risk.

PMID- 29327120
TI  - Readmission and reoperation after midurethral sling.
AB  - INTRODUCTION AND HYPOTHESIS: We aimed to determine the rate of readmission and
      reoperation for patients undergoing midurethral sling (MUS) placement for stress
      urinary incontinence (SUI). METHODS: The American College of Surgeons National
      Surgical Quality Improvement Program (NSQIP) database was queried to identify all
      isolated MUS placed from 2012 through 2015 using the Current Procedural
      Terminology 4 (CPT-4) code for MUS with or without cystoscopy (57,288 +/-
      52,000). The cohort was then reviewed for unplanned, related readmissions and
      reoperations within 30 days of MUS placement. RESULTS: Isolated MUS was placed in
      9910 patients. Fifty-eight (0.59%) patients were readmitted and 81 (0.82%) had
      reoperation. The most common indications for readmission were related to the
      urinary tract, i.e., urinary retention (27.6%), non-surgical-site-related
      infection (15.5%), and medical related issues (15.5%) The most common indications
      for reoperation were urinary tract (60.5%), gastrointestinal (7.4%), and
      gynecologic, i.e., examination under anesthesia (6.2%). Body mass index (BMI) was
      less (p = 0.001), and operative time (p = 0.014) and length of stay (LOS) (p =
      0.001) longer in patients who were readmitted. Those who underwent reoperation
      had longer LOS than those who did not have reoperation (p < 0.001). Upon
      multivariate analysis, BMI <25 (all p < 0.05) and longer LOS maintained
      statistical significance as risk factors for those who experienced readmission or
      reoperation (p = 0.0406, p < 0001). CONCLUSIONS: Isolated MUS placement has low
      30-day readmission and reoperation rates. Increased LOS was associated with
      readmission, while increased LOS and BMI <25 were associated with reoperation
      within 30 days.

PMID- 29327118
TI  - Effect of CPAP therapy on liver disease in patients with OSA: a review.
AB  - Obstructive sleep apnea (OSA) may play an important role in the progression of
      nonalcoholic fatty liver disease (NAFLD).The effect of continuous positive airway
      pressure (CPAP) treatment, the first-line therapy for OSA, on liver disease in
      OSA patients is still debated. We provide this review of previous studies to
      summarize the effects of CPAP treatment on liver disease in OSA patients in
      aspects of liver function, liver steatosis, fibrosis, and incidence of liver
      disease. CPAP treatment may be beneficial to liver disease in subjects with OSA
      independent of metabolic risk factors, but a sufficiently long therapeutic
      duration (perhaps greater than 3 months) may be needed to achieve these positive
      effects. Though the mechanism of impact of CPAP treatment on liver in OSA
      patients is unclear, the influence of CPAP treatment on the factors of the "Two
      hit" hypothesis (insulin resistance, fatty acids dysregulation, oxidative stress,
      and inflammation) may be a reasonable explanation.

PMID- 29327121
TI  - Recognition of Association Between Blood Stasis Syndrome and Traumatic Injury
      among Doctors of Korean Medicine: A Cross-Sectional Observation Study.
AB  - OBJECTIVE: To investigate the diagnostic indicators and herbal treatments for
      blood stasis syndrome (BSS) patients with traumatic injuries and to identify the
      association between BSS and traumatic injury in Korea. METHODS: Two-hundred and
      four patients with traumatic injury were recruited from the Gangnam and Daejeon
      branches of Jaseng Hospital of Oriental Medicine between June 2014 and December
      2014. Two independent doctors of Korean medicine (DKMs) determined the diagnosis
      of BSS or non-BSS based on the subjects signs and symptoms. The scores assigned
      to BSS symptoms and DKMs' reasons for diagnosing BSS in patients with traumatic
      injury were investigated. Both medication and herbal prescription records from a
      3-month period were collected for all patients diagnosed with BSS by both DKMs.
      RESULTS: A total of 169 of 204 (82.8%) patients received consistent diagnosis
      related to BSS by two DKMs. Among them, 54.4% (92 cases) were diagnosed with BSS,
      and 45.6% (77 cases) were not diagnosed with BSS. DKMs most frequently cited
      symptoms of recent traumatic injury as justifications for BSS diagnoses, and also
      selected pain-related indicators such as abdominal pain, sharp pain and nocturnal
      pain as important reasons in diagnosing BSS. In addition, an inconsistency in the
      pattern identification theory with respect to traumatic injury was observed.
      Although only 92 cases (54.4%) of patients were diagnosed with BSS, 77.6% of them
      were prescribed decoctions for BSS. CONCLUSIONS: DKMs considered traumatic injury
      could cause BSS, and utilized decoction for BSS in patients with traumatic injury
      without confirming a diagnosis of BSS because they assumed the main symptoms or
      pathologies of traumatic injury to be closely related to BSS.

PMID- 29327122
TI  - Understanding Qi Running in the Meridians as Interstitial Fluid Flowing via
      Interstitial Space of Low Hydraulic Resistance.
AB  - Qi, blood and the meridians are fundamental concepts in Chinese medicine (CM),
      which are components of the human body and maintain physiological function.
      Pathological changes of qi, blood and meridians may lead to discomfort and
      disease. Treatment with acupuncture or herbal medicine aims to regulate qi and
      blood so as to recover normal function of the meridians. This paper explores the
      nature of qi as well as compares and correlates them with the structures of the
      human body. We propose a conceptualization of qi as being similar to the
      interstitial fluid, and the meridians as being similar to interstitial space of
      low hydraulic resistance in the body. Hence, qi running in the meridians can be
      understood as interstitial fluid flowing via interstitial space of low hydraulic
      resistance.

PMID- 29327123
TI  - Text Mining of Rheumatoid Arthritis and Diabetes Mellitus to Understand the
      Mechanisms of Chinese Medicine in Different Diseases with Same Treatment.
AB  - OBJECTIVE: To identify the commonalities between rheumatoid arthritis (RA) and
      diabetes mellitus (DM) to understand the mechanisms of Chinese medicine (CM) in
      different diseases with the same treatment. METHODS: A text mining approach was
      adopted to analyze the commonalities between RA and DM according to CM and
      biological elements. The major commonalities were subsequently verified in RA and
      DM rat models, in which herbal formula for the treatment of both RA and DM
      identified via text mining was used as the intervention. RESULTS: Similarities
      were identified between RA and DM regarding the CM approach used for diagnosis
      and treatment, as well as the networks of biological activities affected by each
      disease, including the involvement of adhesion molecules, oxidative stress,
      cytokines, T-lymphocytes, apoptosis, and inflammation. The Ramulus Cinnamomi
      Radix Paeoniae Alba-Rhizoma Anemarrhenae is an herbal combination used to treat
      RA and DM. This formula demonstrated similar effects on oxidative stress and
      inflammation in rats with collagen-induced arthritis, which supports the text
      mining results regarding the commonalities between RA and DM. CONCLUSION:
      Commonalities between the biological activities involved in RA and DM were
      identified through text mining, and both RA and DM might be responsive to the
      same intervention at a specific stage.

PMID- 29327124
TI  - Puerarin Up-regulates Methyl-CpG Binding Protein 2 Phosphorylation in Hippocampus
      of Vascular Dementia Rats.
AB  - OBJECTIVE: To observe the effect of puerarin on methyl-CpG binding protein 2
      (MeCP2) phosphorylation (pMeCP2) in the hippocampus of a rat model of vascular
      dementia (VD). METHODS: Thirty-six healthy Sprague-Dawley rats were randomly
      assigned to the sham-operated group, dementia group and puerarintreated group
      using a random number table (n=12 per group). The modifified permanent bilateral
      common carotid artery occlusion method was used to establish the VD model. The
      sham-operated and dementia groups were given 2 mL/d of saline, while the puerarin
      treated group was given 100 mg/(kg*d) of puerarin for 17 days. The learning and
      memory abilities were evaluated by the Morris water maze test. Hematoxylin-eosin
      staining, immunohistochemical (IHC) staining and Western blot analysis were
      carried out to observe changes in neuron morphology and in level of pMeCP2 in the
      hippocampus, respectively. RESULTS: The morphologies of rat hippocampal neurons
      in the puerarintreated group were markedly improved compared with the dementia
      group. The escape latency of the dementia group was significantly longer than the
      sham-operated group (P<0.05), while the puerarin-treated group was obviously
      shorter than the dementia group (P<0.05). Cross-platform times of the dementia
      group were signifificantly decreased compared with the sham-operated group
      (P<0.05), while the puerarin-treated group was obviously increased compared with
      the dementia group (P<0.05). IHC staining showed no significant difference in the
      number of MeCP2 positive cells among 3 groups (P>0.05). The number of pMeCP2
      positive cells in the CA1 region of hippocampus in the dementia group was
      signifificantly increased compared with the sham-operated group, and the puerarin
      treated group was signifificantly increased compared with the dementia group
      (both P<0.05). Western blot analysis showed no signifificant difference of MeCP2
      expression among 3 groups (P>0.05). The expression of pMeCP2 in the dementia
      group was signifificantly increased compared with the sham-operated group, while
      it in the puerarin-treated group was signifificantly increased compared with the
      dementia group (P<0.05). CONCLUSION: Puerarin could play a role in the protection
      of nerve cells through up-regulating pMeCP2 in the hippocampus, improving neuron
      morphologies, and enhancing learning and memory ablities in a rat model of VD.

PMID- 29327126
TI  - Antipyretic Effect of Herba Ephedrae-Ramulus Cinnamomi Herb Pair on Yeast-Induced
      Pyrexia Rats: A Metabolomics Study.
AB  - OBJECTIVE: To investigate the antipyretic mechanism of Herba Ephedrae (Eph)
      Ramulus Cinnamomi (RC) herb pair on yeast-induced pyrexia in rats. METHODS:
      Totally 30 qualified male SD rats were randomly assigned to the normal control
      (NC) group, the pyrexia model (model) group, the Eph, RC and Eph-RC treatment
      groups by a random digital table, 6 rats in each group. Each rat received a 20%
      aqueous suspension of yeast (10 mL/kg) except the NC group. The 3 treatment
      groups were administered 8.1, 5.4 and 13.5 g/kg Eph, RC and Eph-RC respectively
      at 5 and 12 h after yeast injection, the NC group and the model groups were
      administered equal volume of distilled water. Rectal temperatures were measured
      at 0, 6, 8, 10, 12, 15, 18, 24 and 30 h and urine was collected prior to yeast
      injection and at 6, 10, 18, 24, 30, and 36 h after yeast injection. Then urine
      metabolomic profiling by gas chromatography tandem mass spectrometry, coupled
      with multivariate statistical analysis and pattern recognition techniques were
      used to explore the antipyretic effects of Eph-RC. Partial least squares
      discriminate analysis was used to analyze the metabolomics dataset including
      classification and regression in metabolomics plot profiling. RESULTS: Compared
      with the NC group, rectal temperatures were significantly higher in the model
      group (P<0.01), while 3 treatment groups decreased significantly compared with
      the model group (P<0.05 or P<0.01). Rectal temperatures of Eph-RC-treated rats
      started to go down at 6 h, and markedly decreased at 8, 12, 15, 18 and 24 h
      (P<0.05 or P<0.01), while those of the Eph and RC groups had decreased firstly at
      8 h and were markedly lower at 12 h (P<0.05 or P<0.01). Seventeen potential
      biomarkers related to pyrexia were confirmed and identified, including pyruvic
      acid, L-phenylalanine, L-tyrosine, phenylacetic acid, hippuric acid, succinic
      acid, citrate and so on. Eight potential alterations of metabolic pathways
      including phenylalanine metabolism, citrate cycle, tryptophan metabolism,
      biosynthesis of valine, leucine and isoleucine, were identified in relation to
      the antipyretic effects of Eph-RC using MetPA software. CONCLUSION: The
      antipyretic effect of Eph-RC herb pair on yeast-induced pyrexia in rats involved
      correction of perturbed amino acid, fatty acid, and carbohydrate metabolism
      according to the metabolic pathway analysis with MetPA.

PMID- 29327127
TI  - A child with painless left wrist swelling.

PMID- 29327125
TI  - Icariin Improves Cognitive Impairment after Traumatic Brain Injury by Enhancing
      Hippocampal Acetylation.
AB  - OBJECTIVE: To examine the effect of icariin (ICA) on the cognitive impairment
      induced by traumatic brain injury (TBI) in mice and the underlying mechanisms
      related to changes in hippocampal acetylation level. METHODS: The modifified free
      fall method was used to establish the TBI mouse model. Mice with post-TBI
      cognitive impairment were randomly divided into 3 groups using the randomised
      block method (n=7): TBI (vehicle-treated), low-dose (75 mg/kg) and high-dose (150
      mg/kg) of ICA groups. An additional sham-operated group (vehicle-treated) was
      employed. The vehicle or ICA was administrated by gavage for 28 consecutive days.
      The Morris water maze (MWM) test was conducted. Acetylcholine (ACh) content, mRNA
      and protein levels of choline acetyltransferase (ChAT), and protein levels of
      acetylated H3 (Ac-H3) and Ac-H4 were detected in the hippocampus. RESULTS:
      Compared with the sham-operated group, the MWM performance, hippocampal ACh
      content, mRNA and protein levels of ChAT, and protein levels of Ac-H3 and Ac-H4
      were signifificantly decreased in the TBI group (P<0.05). High-dose of ICA
      signifificantly ameliorated the TBI-induced weak MWM performance, increased
      hippocampal ACh content, and mRNA and protein levels of ChAT, as well as Ac-H3
      protein level compared with the TBI group (P<0.05). CONCLUSION: ICA improved post
      TBI cognitive impairment in mice by enhancing hippocampal acetylation, which
      improved hippocampal cholinergic function and ultimately improved cognition.

PMID- 29327128
TI  - Isolated avulsion fracture of the first metatarsal base at the peroneus longus
      tendon attachment: a case report.
AB  - Avulsion fractures of the first metatarsal (MT1) base at the peroneus longus (PL)
      tendon attachment are rare and may be undiagnosed during an emergency visit. If
      the injury is not treated properly, chronic pain or persistent impairment for
      inversion and plantar-flexion of the first ray may occur. This case report
      presents a 30-year-old woman who presented 10 weeks post trauma to a foot and
      ankle surgeon due to a swollen right midfoot with diffuse tenderness over the
      medial Lisfranc joint. Further evaluation showed an isolated avulsion fracture of
      the first metatarsal, which was undiagnosed during the emergent visit following
      the accident. In this case, the patient was successfully treated conservatively.
      The goal of this article is to raise awareness of this rare injury for
      radiologists and orthopedic surgeons.

PMID- 29327129
TI  - Quantification of osteoblastic activity in epiphyseal growth plates by
      quantitative bone SPECT/CT.
AB  - OBJECTIVE: Quantifying the function of the epiphyseal plate is worthwhile for the
      management of children with growth disorders. The aim of this retrospective study
      was to quantify the osteoblastic activity at the epiphyseal plate using the
      quantitative bone SPECT/CT. MATERIALS AND METHODS: We enrolled patients under the
      age of 20 years who received Tc-99m hydroxymethylene diphosphonate bone
      scintigraphy acquired by a quantitative SPECT/CT scanner. The images were
      reconstructed by ordered subset conjugate-gradient minimizer, and the uptake on
      the distal margin of the femur was quantified by peak standardized uptake value
      (SUVpeak). A public database of standard body height was used to calculate growth
      velocities (cm/year). RESULTS: Fifteen patients (6.9-19.7 years, 9 female, 6
      male) were enrolled and a total of 25 legs were analyzed. SUVpeak in the
      epiphyseal plate was 18.9 +/- 2.4 (average +/- standard deviation) in the
      subjects under 15 years and decreased gradually by aging. The SUVpeak correlated
      significantly with the age- and sex-matched growth velocity obtained from the
      database (R2 = 0.83, p < 0.0001). CONCLUSION: The SUV measured by quantitative
      bone SPECT/CT was increased at the epiphyseal plates of children under the age of
      15 years in comparison with the older group, corresponding to higher osteoblastic
      activity. Moreover, this study suggested a correlation between growth velocity
      and the SUV. Although this is a small retrospective pilot study, the objective
      and quantitative values measured by the quantitative bone SPECT/CT has the
      potential to improve the management of children with growth disorder.

PMID- 29327132
TI  - Impact of ENIGMA trials on nitrous oxide: a survey of Canadian anesthesiologists
      and residents.

PMID- 29327131
TI  - Renal vein thrombosis complicating severe acute pyelonephritis with renal
      abscesses and associated bacteraemia caused by extended-spectrum beta-lactamase
      producing Escherichia coli.
AB  - Acute pyelonephritis might be complicated by the formation of renal and perirenal
      abscesses and very rarely by renal vein thrombosis, which is a life-threatening
      condition. The main causative agents of acute pyelonephritis are
      enterobacteriaceae with the incidence of extended-spectrum beta-lactamase (ESBL)
      producing strains increasing worldwide. We present the case of a 71-year-old
      Greek man with history of diabetes mellitus and recent hospitalization, who
      suffered from severe pyelonephritis with renal abscesses formation and associated
      bacteraemia caused by ESBL-producing Escherichia coli, complicated by extensive
      thrombosis of the ipsilateral renal vein and its branches, protruding also in the
      inferior venal cava. Our patient was effectively treated with anticoagulants and
      targeted antibiotic therapy, respectively, consisted of low molecular weight
      heparin transitioned to oral acenocoumarol for 3 months and 2-week course of
      intravenous meropenem followed by oral fosfomycin for additional 3 weeks as
      quidded by clinical and computed tomographic follow-up. In conclusion, in
      complicated urinary infections, caused by ESBL-producing enterobacteriaceae, oral
      fosfomycin might represent an effective option for step-down therapy of
      carbapenems, allowing the shortness of the duration of patient's hospitalization
      and carbapenem use.

PMID- 29327133
TI  - Mobile ascending aortic mass presenting as acute myocardial infarction.

PMID- 29327134
TI  - Management strategies for unintentional dural puncture: a Canadian experience
      survey in an academic setting.

PMID- 29327135
TI  - Acquiring and maintaining point-of-care ultrasound (POCUS) competence for
      anesthesiologists.
AB  - PURPOSE: Point-of-care ultrasound (POCUS) involves the bedside use of ultrasound
      to answer specific diagnostic questions and to assess real-time physiologic
      responses to treatment. Although POCUS has become a well-established resource for
      emergency and critical care physicians, anesthesiologists are still working to
      obtain POCUS skills and to incorporate them into routine practice. This review
      defines the benefits of POCUS to anesthesia practice, identifies challenges to
      establishing POCUS in routine anesthesia care, and offers solutions to help guide
      its incorporation going forward. PRINCIPAL FINDINGS: Benefits to POCUS include
      improving the sensitivity and specificity of the physical examination and helping
      to guide patient treatment. The challenges to establishing POCUS as a standard in
      anesthesia practice include developing and maintaining competence. There is a
      need to develop standards of practice and a common language between specialties
      to facilitate training and create guidelines regarding patient management.
      CONCLUSIONS: Presently, our specialty requires consensus by expert stakeholders
      to address issues of competence, certification, development of standards and
      terminology, and the management of unexpected diagnoses. To promote POCUS
      competency in our discipline, we support its incorporation into anesthesiology
      curricula and training programs and the continuing professional development of
      POCUS-related activities at a national level.

PMID- 29327136
TI  - Signal Detection for Recently Approved Products: Adapting and Evaluating Self
      Controlled Case Series Method Using a US Claims and UK Electronic Medical Records
      Database.
AB  - INTRODUCTION: The Self-Controlled Case Series (SCCS) method has been widely used
      for hypothesis testing, but there is limited evidence of its performance for
      safety signal detection. OBJECTIVE: The objective of this study was to evaluate
      SCCS for signal detection on recently approved products. METHODS: A retrospective
      study covered the period after three recently marketed drugs were launched
      through to 31 December 2010 using The Health Improvement Network, a UK primary
      care database, and Optum, a US claims database. The SCCS method was applied to
      examine five heterogenous outcomes with desvenlafaxine and escitalopram and six
      outcomes with adalimumab for Signals of Disproportional Recording (SDRs); a
      positive finding was determined to be when the lower bound of 95% Confidence
      Interval of the incidence rate ratio (IRR) estimate was >  1. Multiple design
      choices were tested and the trend in IRR estimates over calendar time for one
      drug event pair was examined. RESULTS: All six outcomes with adalimumab, three of
      five outcomes with desvenlafaxine, and four of five outcomes with escitalopram
      had SDRs. SCCS highlighted all acute events in the primary analysis but was less
      successful with slower-onset outcomes. Performance varied by risk period
      definition. Changes in IRR estimates over quarterly intervals for adalimumab with
      herpes zoster showed marked higher SDR within 9 months of drug launch.
      CONCLUSION: SCCS shows promise for signal detection: it may highlight known
      associations for recent marketed products and has potential for early signal
      identification. SCCS performance varied by design choice and the nature of both
      exposure and event pair. Future work is needed to determine how effective the
      approach is in prospective testing and determining the performance
      characteristics of the approach.

PMID- 29327130
TI  - Main steps in DNA double-strand break repair: an introduction to homologous
      recombination and related processes.
AB  - DNA double-strand breaks arise accidentally upon exposure of DNA to radiation and
      chemicals or result from faulty DNA metabolic processes. DNA breaks can also be
      introduced in a programmed manner, such as during the maturation of the immune
      system, meiosis, or cancer chemo- or radiotherapy. Cells have developed a variety
      of repair pathways, which are fine-tuned to the specific needs of a cell.
      Accordingly, vegetative cells employ mechanisms that restore the integrity of
      broken DNA with the highest efficiency at the lowest cost of mutagenesis. In
      contrast, meiotic cells or developing lymphocytes exploit DNA breakage to
      generate diversity. Here, we review the main pathways of eukaryotic DNA double
      strand break repair with the focus on homologous recombination and its various
      subpathways. We highlight the differences between homologous recombination and
      end-joining mechanisms including non-homologous end-joining and microhomology
      mediated end-joining and offer insights into how these pathways are regulated.
      Finally, we introduce noncanonical functions of the recombination proteins, in
      particular during DNA replication stress.

PMID- 29327137
TI  - MicroRNA expression in SMARCB1/INI1-deficient sinonasal carcinoma: a
      clinicopathological and molecular genetic study.

PMID- 29327138
TI  - Handling and reporting of transperineal template prostate biopsy in Europe: a web
      based survey by the European Network of Uropathology (ENUP).
AB  - Transperineal template prostate biopsies (TTPB) are performed for assessments
      after unexpected negative transrectal ultrasound biopsies (TRUSB), correlation
      with imaging findings and during active surveillance. The impact of TTPBs on
      pathology has not been analysed. The European Network of Uropathology (ENUP)
      distributed a survey on TTPB, including how specimens were received, processed
      and analysed. Two hundred forty-four replies were received from 22 countries with
      TTPBs seen by 68.4% of the responders (n = 167). Biopsies were received in more
      than 12 pots in 35.2%. The number of cores embedded per cassette varied between 1
      (39.5%) and 3 or more (39.5%). Three levels were cut in 48.3%, between 2 and 3
      serial sections in 57.2% and unstained spare sections in 45.1%. No statistical
      difference was observed with TRUSB management. The number of positive cores was
      always reported and the majority gave extent per core (82.3%), per region (67.1%)
      and greatest involvement per core (69.4%). Total involvement in the whole series
      and continuous/discontinuous infiltrates were reported in 42.2 and 45.4%,
      respectively. The majority (79.4%) reported Gleason score in each site or core,
      and 59.6% gave an overall score. A minority (28.5%) provided a map or a diagram.
      For 19%, TTPB had adversely affected laboratory workload with only 27% managing
      to negotiate extra costs. Most laboratories process samples thoroughly and report
      TTPB similarly to TRUSB. Although TTPB have caused considerable extra work, it
      remains uncosted in most centres. Guidance is needed for workload impact and
      minimum standards of processing if TTPB work continues to increase.

PMID- 29327139
TI  - Galectin-3 levels relate in children to total body fat, abdominal fat, body fat
      distribution, and cardiac size.
AB  - : Galectin-3 has recently been proposed as a novel biomarker for cardiovascular
      disease in adults. The purpose of this investigation was to assess relationships
      between galectin-3 levels and total body fat, abdominal fat, body fat
      distribution, aerobic fitness, blood pressure, left ventricular mass, left atrial
      size, and increase in body fat over a 2-year period in a population-based sample
      of children. Our study included 170 children aged 8-11 years. Total fat mass and
      abdominal fat were measured by dual-energy x-ray absorptiometry (DXA). Body fat
      distribution was expressed as abdominal fat/total fat mass. Maximal oxygen uptake
      was assessed by indirect calorimetry during a maximal exercise test and scaled to
      body mass. Systolic and diastolic blood pressure and pulse pressure were
      measured. Left atrial size, left ventricular mass, and relative wall thickness
      were measured by echocardiography. Frozen serum samples were analyzed for
      galectin-3 by the Proximity Extension Assay technique. A follow-up DXA scan was
      performed in 152 children 2 years after the baseline exam. Partial correlations,
      with adjustment for sex and age, between galectin-3 versus body fat measurements
      indicated weak to moderate relationships. Moreover, left atrial size, left
      ventricular mass, and relative wall thickness and pulse pressure were also
      correlated with galectin-3. Neither systolic blood pressure nor maximal oxygen
      uptake was correlated with galectin-3. There was also a correlation between
      galectin-3 and increase in total body fat over 2 years, while no such
      correlations were found for the other fat measurements. CONCLUSION: More body fat
      and abdominal fat, more abdominal body fat distribution, more left ventricular
      mass, and increased left atrial size were all associated with higher levels of
      galectin-3. Increase in total body fat over 2 years was also associated with
      higher levels of galectin-3. What is Known: * Galectin-3 has been linked to
      obesity and been proposed to be a novel biomarker for cardiovascular disease in
      adults. * Information on this subject in children is very scarce. What is New: *
      The present study demonstrates a relationship between galectin-3 levels and total
      body fat, abdominal fat, body fat distribution, cardiac size and geometry, and
      increase in total body fat over 2 years in young children.

PMID- 29327141
TI  - Theoretical study on benzoheterocycle based energetic materials, effect of
      heterocyclic-fused, conjugation, hydrogen bond, and substitutional group on the
      detonation performance.
AB  - In this paper, four series of benzoheterocycle based energetic materials (EMs)
      have been designed to plan out a strategy to improve the density and safety of
      EMs, such as combining the insensitive group with aminobenzene ring and the high
      energetic nitramine explosives, benzo-heterocycle mother ring, designing multi
      nitrogen heterocycles with a conjugated system containing N-N and C-N high energy
      bonds, and hydrogen bonding. Their optimized structure and detonation properties
      were first calculated and discussed using DFT methods. After calculation, these
      designed explosives all showed good detonation from 7352 m/s to 8788 m/s. Among
      them, the compounds with six nitro groups, 1c, 2c, 3c, and 4c, exhibit better
      performance and rather poor impact sensitivity. However, we found that the
      compounds with five nitro groups and one amino group have a limited performance
      reduction and a rapid stability improvement. These four compounds, 1b, 2b, 3b,
      and 4b, have good detonation performance and better stability. Moreover, the
      synthesis routes for these four compounds were also designed. The precursor 4-0
      and mononitro product 4-1 were successfully synthesized. Their 1H NMR, single
      crystal, and elemental analysis were also done to verify the structures.

PMID- 29327142
TI  - Quality of life and disability 12 months after surgery vs. conservative
      management for unruptured brain arteriovenous malformations: Scottish population
      based and Australian hospital-based studies.
AB  - BACKGROUND: Few data are available on disability and quality of life (QOL) after
      surgery versus conservative management for unruptured brain arteriovenous
      malformations (uAVMs). OBJECTIVE: The aim of this study was to test the
      hypothesis that QOL and disability are worse after surgery +/- preoperative
      embolisation for uAVM compared with conservative management. METHODS: We included
      consecutive patients diagnosed with uAVM from a prospective population-based
      study in Scotland (1999-2003; 2006-2010) and a prospective hospital-based series
      in Australia (2011-2015). We assessed outcomes on the modified Rankin Scale (mRS)
      and the Short Form (SF)-36 at ~ 12 months after surgery or conservative treatment
      and compared these groups using continuous ordinal regression in the two cohorts
      separately. RESULTS: Surgery was performed for 29% of all uAVM cases diagnosed in
      Scotland and 84% of all uAVM referred in Australia. There was no statistically
      significant difference between surgery and conservative management at 12 months
      among 79 patients in Scotland (mean SF-36 Physical Component Score (PCS) 39 [SD
      14] vs. 39 [SD 13]; mean SF-36 Mental Component Score (MCS) 38 [SD 14] vs. 39 [SD
      14]; mRS > 1, 24 vs. 9%), nor among 37 patients in Australia (PCS 51 [SD 10] vs.
      49 [SD 6]; MCS 48 [SD 12] vs. 49 [SD 10]; mRS > 1, 19 vs. 30%). In the Australian
      series, there was no statistically significant change in the MCS and PCS between
      baseline before surgery or conservative management and 12 months. CONCLUSIONS: We
      did not find a statistically significant difference between surgery +/-
      preoperative embolisation and conservative management in disability or QOL at 12
      months.

PMID- 29327140
TI  - Children's experiences of congenital heart disease: a systematic review of
      qualitative studies.
AB  - : We aimed to describe the experiences of children and adolescents with
      congenital heart disease (CHD). Electronic databases were searched until August
      2016. Qualitative studies of children's perspectives on CHD were included. Data
      was extracted using thematic synthesis. From 44 studies from 12 countries
      involving 995 children, we identified 6 themes: disrupting normality (denying the
      diagnosis, oscillating between sickness and health, destabilizing the family
      dynamic), powerlessness in deteriorating health (preoccupation with impending
      mortality, vulnerability to catastrophic complications, exhaustion from medical
      testing), enduring medical ordeals (traumatized by invasive procedures,
      disappointed by treatment failure, displaced by transition, valuing empathy and
      continuity in care, overcoming uncertainty with information), warring with the
      body (losing stamina, distressing inability to participate in sport, distorted
      body image, testing the limits), hampering potential and goals (feeling disabled,
      unfair judgment and exclusion, difficulties with academic achievement, limiting
      attainment and maintenance of life milestones), and establishing one's own pace
      (demarcating disease from life, determination to survive, taking limitations in
      their stride, embracing the positives, finding personal enrichment, relying on
      social or spiritual support). CONCLUSION: Children with CHD feel vulnerable and
      burdened by debilitating physical symptoms, unpredictable complications, and
      discrimination. Clinicians may support patients by sharing recognition of these
      profound psychosocial consequences. What is Known: * CHD is associated with
      difficulties in learning and attention, school absenteeism, decreased endurance,
      poor body image, and peer socialization * What is lesser known is how young
      patients cope with the symptoms, prognostic uncertainty, and treatment burden
      What is New: * We found that children are challenged by lifestyle restrictions,
      fear of invasive procedures, impaired body image, discrimination, and uncertainty
      about the future. Feelings of disempowerment are intensified by the
      unpredictability of disease progression * Thus, strategies to improve outcomes
      include improved patient education on disease and lifestyle management and
      partnership with school teachers and counselors for unique psychosocial support.

PMID- 29327143
TI  - Long-term control and predictors of seizures in intracranial meningioma surgery:
      a population-based study.
AB  - BACKGROUND: The aim of this retrospective study was to investigate the long-term
      seizure control and antiepileptic drug (AED) prescriptions, as well as
      identifying predictors of seizure(s) before and after surgery in a population
      based cohort of operated intracranial meningioma patients. METHODS: A total of
      113 consecutive adult (> 18 years old) patients with newly diagnosed meningioma
      operated at the Karolinska University Hospital between 2006 and 2008 were
      included and followed up until the end of 2015. Data on seizure activity and AED
      prescriptions were obtained through chart review and telephone interview.
      Logistic regression and survival analysis were applied to identify risk factors
      for pre- and postoperative seizures. RESULTS: A total of 21/113 (18.6%) patients
      experienced seizures before surgery of which 8/21 (38.1%) went on to become
      seizure-free after surgery. Thirteen (14%) patients experienced new-onset
      seizures after surgery. The regression analysis revealed tumor diameter >= 3.5 cm
      as a risk factor for preoperative seizures (OR 3.83, 95% CI 1.14-12.87). Presence
      of headache (OR 0.19, 95% CI 0.05-0.76) and skull base tumor location (OR 0.14,
      95% CI 0.04-0.44) decreased the risk of preoperative seizures. Postoperative
      seizures were associated with tumor diameter >= 3.5 cm (OR 2.65, 95% CI 1.06
      6.62) and history of preoperative seizures (OR 3.50, 95% CI 1.55-7.90).
      CONCLUSION: Seizures are common before and after intracranial meningioma surgery.
      Approximately one third of patients with preoperative seizures become seizure
      free on long-term follow-up after surgery, while 14% experienced new-onset
      seizures after surgery. Larger tumor size, absence of headache, and non-skull
      base location were associated with preoperative seizures, while tumor size and
      preoperative seizures were associated with postoperative seizures.

PMID- 29327145
TI  - HLA-DR expression in neonates after cardiac surgery under cardiopulmonary bypass:
      a pilot study.
AB  - Monocyte HLA-DR expression has been reported as a marker of immunosuppression and
      a predictor of sepsis development. However, to date, there is no report on
      monocyte HLA-DR monitoring exclusively in neonates (< 28 days of life) who
      underwent cardiac surgery under cardiopulmonary bypass (CPB), which have a high
      risk of nosocomial infection. In this pilot study, we studied nine neonates with
      a diagnosis of congenital heart disease requiring surgery under CPB. There was a
      significant reduction in monocyte HLA-DR expression for the first two
      postoperative days, as compared to preoperatively (p = 0.004). Moreover, neonates
      who displayed an episode of NI had a dramatically lower HLA-DR expression at day
      4, as compared to neonates without NI (4257 AB/c [2220-5895] vs 14,947 AB/c [9858
      16,960]; p = 0.04). Our preliminary results could indicate that HLA-DR expression
      may be a useful biomarker of immunosuppression-induced secondary infection after
      CPB in neonates.

PMID- 29327146
TI  - Mid-term Outcome of 100 Consecutive Ross Procedures: Excellent Survival, But Yet
      to Be a Cure.
AB  - The Ross procedure offers excellent short-term outcome but the long-term
      durability is under debate. Reinterventions and follow-up of 100 consecutive
      patients undergoing Ross Procedure at our centre (1993-2011) were analysed.
      Follow-up was available for 96 patients (97%) with a median duration of 5.3 (0.1
      17.1) years. Median age of the patient cohort was 15.2 (0.04-58.4) years with 76
      males. 93% had underlying congenital aortic stenosis. Root replacement technique
      was applied in all. The most common valved conduits used for reconstruction of
      the right ventricular outflow tract were homografts (66 patients) and bovine
      jugular vein (ContegraR) graft (31 patients). Additional procedures included Ross
      Konno procedure (14%), resection of subaortic stenosis/myectomy (11%) and
      reduction plasty of the ascending aorta (25%). One patient died within the first
      30 days (1%). Late deaths occurred in 4 patients (4%) 0.5-4.5 years
      postoperatively: causes included pulmonary hypertension due to endocardial
      fibroelastosis (2), subarachnoid haemorrhage (1) and sudden cardiac death (1).
      Five-year survival was 93.6 (95% CI 88.1-99.1)%. Moderate or severe aortic
      (autograft) regurgitation needing reoperation occurred in 8 patients with a 5
      year freedom from autograft reoperation of 98.5 (95.6-100)%. Five-year freedom
      from reintervention (surgery or catheter based) on the right ventricular outflow
      tract conduit was 91.5 (85.5-96.5)%. Univariate predictors of this
      reinterventions were smaller graft size (p = 0.03) and use of a ContegraR graft
      (p = 0.04). Ross procedure can be performed with low mortality and good survival
      in the long term. Most of the reinterventions are related to the neo-right
      ventricular outflow tract and may be partly attributed to the lack of growth.
      While the Ross Procedure remains an invaluable option for aortic valve disease in
      children, new solutions for the neo-pulmonary valve as well as for the less often
      occurring problems on the autograft are needed.

PMID- 29327147
TI  - Post-operative Catheterization Interventions at the Site of Surgery: An
      Application of the CRISP Scoring System.
AB  - Catheter-based interventions in the early post-operative period are performed
      with caution due to concerns for increased procedural risk, particularly across
      fresh suture lines. The recently published CRISP scoring system provides
      prospective risk stratification based on pre-procedural criterion. In an effort
      to refine the assessment of risk in patients undergoing post-operative catheter
      based interventions, the predicted risk of an adverse event based on CRISP scores
      was compared to actual adverse event rates. A single-center, retrospective review
      of patients undergoing catheterization interventions within 6 weeks of cardiac
      surgery was conducted between Jan 2004 and Dec 2014. Patients who underwent
      dilation interventions across fresh suture lines (group 1) were compared to
      patients who underwent interventional procedures at other sites (group 2), and a
      CRISP score was calculated for all patients. Patients receiving only surveillance
      biopsies were excluded. Sixty-eight patients underwent 100 interventional
      procedures. Group 1 was composed of 44 patients receiving 64 interventions, while
      group 2 had 24 patients who underwent 36 interventions. Group 1 was comprised
      significantly more single ventricles and patients were smaller/younger. Group 1
      had a significantly higher median CRISP score, but both groups were within
      Category 4. The rates of adverse events were similar between groups and
      comparable to predicted rates with the CRISP scoring system. Catheter-based
      interventions in the early post-operative period can be performed with no
      significant increase in the risk of serious adverse events when intervening
      across fresh suture lines. The CRISP scoring system can be a valuable tool in pre
      procedural counseling of high-risk post-operative patients.

PMID- 29327149
TI  - Gestational diabetes and risk of cardiovascular disease up to 25 years after
      pregnancy: a retrospective cohort study.
AB  - AIMS: The risk of cardiovascular disease in women with gestational diabetes is
      poorly understood. We sought to determine whether gestational diabetes increases
      the risk of cardiovascular disease more than two decades after pregnancy.
      METHODS: We carried out a retrospective cohort study of 1,070,667 women who
      delivered infants in hospitals within Quebec, Canada, between 1989 and 2013. We
      followed 67,356 women with gestational diabetes and 1,003,311 without gestational
      diabetes for a maximum of 25.2 years after the index delivery. The main outcome
      measures were hospitalization for ischemic heart disease, myocardial infarction,
      coronary angioplasty, coronary artery bypass graft, and other cardiovascular
      disorders. We used Cox regression to estimate hazard ratios (HR) and 95%
      confidence intervals (CI) comparing women with gestational diabetes to no
      gestational diabetes, adjusted for age, parity, socioeconomic deprivation, time
      period, and preeclampsia. RESULTS: Women with gestational diabetes had a higher
      cumulative incidence of hospitalization for cardiovascular disease 25 years after
      delivery (190.8 per 1000 women) compared with no gestational diabetes (117.8 per
      1000 women). Gestational diabetes was associated with a higher risk of ischemic
      heart disease (HR 1.23, 95% CI 1.12-1.36), myocardial infarction (HR 2.14, 95% CI
      1.15-2.47), coronary angioplasty (HR 2.23, 95% CI 1.87-2.65), and coronary artery
      bypass graft (HR 3.16, 95% CI 2.24-4.47). CONCLUSIONS: In this population of
      pregnant women, gestational diabetes was associated with an increased risk of
      heart disease 25 years after delivery. Women with gestational diabetes may merit
      closer monitoring for cardiovascular disease prevention after pregnancy.

PMID- 29327148
TI  - Autoantibodies against zinc transporter 8 are related to age and metabolic state
      in patients with newly diagnosed autoimmune diabetes.
AB  - AIMS: To assess the prevalence of ZnT8-ab and its correlation to other autoimmune
      markers and diabetic ketoacidosis occurrence in children and adults with T1DM
      onset. METHODS: The study included 367 patients (218 children; 149 adults) at the
      T1DM onset. Selected diabetes-related autoantibodies such as GAD-ab, IA2-ab, ZnT8
      ab were tested before the initiation of insulin therapy. Diabetic ketoacidosis
      was defined as glucose concentration > 13.9 mmol/l, pH < 7.30, concentration of
      HCO3 < 15 mmol/l, presence of ketone bodies in the blood and urine. RESULTS: The
      autoantibodies pattern differs in both study groups. Children were mostly
      positive for two (37.8%) and three (49.5%) autoantibodies, whereas adults for one
      (32.2%) and two (30.7%). The most frequently detected autoantibodies in youth
      were ZnT8-ab (81.1%) and IA2-ab (80.7%), while in adults GAD-ab (74.8%). ZnT8-ab
      (p < 0.0001) titers were significantly higher in children, but adults had higher
      titer of GAD-ab (p < 0.0001) and IA2-ab (p < 0.0001). Children developed more
      frequently diabetic ketoacidosis (28.4 vs. 10.7%, p = 0.0002). ZnT8-ab (p =
      0.002) and IA2-ab (p = 0.008) were reported mostly in individuals with
      ketoacidosis. A correlation between the number of positive antibodies and the
      severity of ketoacidosis was observed (Rs - 0.129 p = 0.014). ZnT8-ab were
      associated with a greater risk of ketoacidosis independent of gender, age group
      and the autoantibodies number [OR = 2.44 (95% CI 1.0-5.94), p = 0.04].
      CONCLUSIONS: Children are at greater risk of ketoacidosis at the diagnosis of
      diabetes. ZnT8-ab and IA2-ab are commonly detected in children, while adults have
      frequently higher titer of GAD-ab. ZnT8-ab are associated with more acute
      diabetes onset.

PMID- 29327150
TI  - Levels of serum uric acid at admission for hypoglycaemia predict 1-year
      mortality.
AB  - AIMS: Hypoglycaemia represents a critical burden with clinical and social
      consequences in the management of diabetes. Serum uric acid (SUA) has been
      associated with cardiovascular diseases (CVD), but no conclusive findings are
      available nowadays in patients suffering from hypoglycaemia. We investigated
      whether SUA levels at the time of hypoglycaemia could predict all-cause mortality
      after 1-year follow-up. METHODS: In total, 219 patients admitted to the Emergency
      Department (ED) of Ospedale Policlinico S. Martino of Genoa (Italy) have been
      enrolled between January 2011 and December 2014. The primary endpoint of the
      study consisted in determining whether SUA levels at the time of ED admission
      could predict the occurrence of death after 1 year. RESULTS: The majority of
      patients were diabetic, especially type 2. CVD and chronic kidney disease were
      prevalent comorbidities. By a cut-off value obtained by the receiver operating
      characteristic curve analysis, a Kaplan-Meier analysis demonstrated that patients
      with SUA levels > 5.43 mg/dL were more prone to death after 1 year compared to
      those with lower SUA levels. The risk of death increased with high SUA levels
      both in the univariate and the multivariate models including estimated glomerular
      filtration rate, C-reactive protein, type of diabetes, and age-adjusted Charlson
      comorbidity index. CONCLUSIONS: SUA could be useful as a predictor of 1-year
      mortality in hypoglycaemic patients, irrespective of severe comorbidities notably
      increasing the risk of death in these frail patients.

PMID- 29327151
TI  - Impact of Admission Hypertension on Rates of Acute Kidney Injury in Intracerebral
      Hemorrhage Treated with Intensive Blood Pressure Control.
AB  - BACKGROUND: Current guidelines recommend that rapid systolic blood pressure (SBP)
      lowering to 140 mmHg may be considered in intracerebral hemorrhage (ICH) patients
      regardless of initial SBP. However, limited safety data exist in patients
      presenting with varying degrees of severe hypertension. The purpose of this study
      was to determine whether there was an increased risk of acute kidney injury (AKI)
      based upon degree of presentation hypertension in ICH patients whose blood
      pressure was reduced intensively. METHODS: This retrospective, cohort study
      evaluated ICH patients treated with intensive blood pressure control (SBP <=140
      mmHg) who presented with three degrees of presentation hypertension: mild (SBP
      141-179 mmHg), moderate (SBP 180-219 mmHg), and severe (SBP >= 220 mmHg).
      Univariate analysis of demographics variables, ICH severity, and factors known to
      impact AKI was conducted between the three groups. Post hoc testing was used to
      compare differences between specific groups, with a Bonferroni correction
      adjusting for multiple comparisons. Additionally, we conducted logistic
      regression analysis to determine whether baseline SBP group independently
      predicted AKI. RESULTS: We included 401 patients (177 with mild, 124 with
      moderate, and 100 with severe hypertension). There was a significant increase in
      the prevalence of AKI between groups, with the severe group experiencing the
      highest rate (p < 0.001). The presence of severe hypertension was also found to
      independently predict AKI development (odds ratio 2.6; p < 0.001). CONCLUSION:
      Our study observed higher rates of AKI in patients presenting with severe
      hypertension. Further research is needed to determine the most appropriate
      strategies for managing blood pressure in ICH patients presenting with higher
      SBP.

PMID- 29327152
TI  - The Prevalence and Impact of Status Epilepticus Secondary to Intracerebral
      Hemorrhage: Results from the US Nationwide Inpatient Sample.
AB  - BACKGROUND: Status epilepticus (SE) has been identified as a predictor of
      morbidity and mortality in many acute brain injury patient populations. We aimed
      to assess the prevalence and impact of SE after intracerebral hemorrhage (ICH) in
      a large patient sample to overcome limitations in previous small patient sample
      studies. METHODS: We queried the Nationwide Inpatient Sample for patients
      admitted for ICH from 1999 to 2011, excluding patients with other acute brain
      injuries. Patients were stratified into SE diagnosis and no SE diagnosis cohorts.
      We identified independent risk factors for SE and assessed the impact of SE on
      morbidity and mortality with multivariable logistic regression models. Logistic
      regression was used to evaluate the trend in SE diagnoses over time as well.
      RESULTS: SE was associated with significantly increased odds of both mortality
      and morbidity (odds ratios (OR) 1.18 [confidence intervals (CI) 1.01-1.39], and
      OR 1.53 [CI 1.22-1.91], respectively). Risk factors for SE included female sex
      (OR 1.17 [CI 1.01-1.35]), categorical van Walraven score (vWr 5-14: OR 1.68 [CI
      1.41-2.01]; vWr > 14: OR 3.77 [CI 2.98-4.76]), sepsis (OR 2.06 [CI 1.58-2.68]),
      and encephalopathy (OR 3.14 [CI 2.49-3.96]). Age was found to be associated with
      reduced odds of SE (OR 0.97 [CI 0.97-0.97]). From 1999 to 2011, prevalence of SE
      diagnosis increased from 0.25 to 0.61% (p < 0.001). Factors associated with SE
      were female sex, medium and high risk vWr score, sepsis, and encephalopathy.
      Independent predictors associated with increased mortality from SE were increased
      age, pneumonia, myocardial infarction, cardiac arrest, and sepsis. CONCLUSIONS:
      SE is a significant, likely underdiagnosed, predictor of morbidity and mortality
      after ICH. Future studies are necessary to better identify which patients are at
      highest risk of SE to guide resource utilization.

PMID- 29327153
TI  - The Effect of Therapeutic Mild Hypothermia on Brain Microvascular Endothelial
      Cells During Ischemia-Reperfusion Injury.
AB  - BACKGROUND: To determine the cerebral protective effects of mild hypothermia (MH)
      on cerebral microcirculation. METHODS: We established ischemia-reperfusion (I/R)
      injury and MH treatment models with rat brain microvascular endothelial cells
      (RBMECs) in vitro and examined the apoptotic changes. The cultured RBMECs were
      randomly divided into the control group, I/R group, and MH group, which was
      further divided into two subgroups: intra-ischemia hypothermia (IIH) and post
      ischemia hypothermia (PIH). Cell morphological changes were assessed using
      fluorescence microscopy. Apoptotic rates were obtained by flow cytometry.
      Expressions of caspase-3, Bax, and Bcl-2 were analyzed by Western blot. RESULTS:
      I/R injury in vitro induced apoptosis of RBMECs. The apoptotic rates in the
      control group, I/R group, and MH group were 0.13, 19.04, and 13.13%, respectively
      (P < 0.01). Compared with the I/R group, the MH group showed a significant
      decrease in the number of apoptotic cells, mainly in stage I apoptotic cells (P <
      0.0083). The caspase-3 and Bax expressions were significantly enhanced (P < 0.05)
      in RBMECs after I/R injury, while substantial decreases in Bcl-2 expression were
      noted (P < 0.05). Following MH intervention, the increase in caspase-3 and Bax
      expression was suppressed (P < 0.05), while Bcl-2 expression significantly
      increased. The apoptotic rates or protein expressions between the two subgroups
      were not different significantly (P > 0.05). CONCLUSIONS: These results indicate
      that MH could inhibit RBMEC apoptosis by preventing pro-apoptotic cells and early
      apoptotic cells from progressing to intermediate and advanced stages. This may be
      due to the effect of MH on I/R-induced apoptotic gene expression changes.

PMID- 29327154
TI  - Effect of Synthesis Method of La1 - xSr x MnO3 Manganite Nanoparticles on Their
      Properties.
AB  - Nanoparticles of lanthanum-strontium manganite were synthesized via different
      methods, namely, sol-gel method, precipitation from non-aqueous solution, and
      precipitation from reversal microemulsions. It was shown that the use of organic
      compounds and non-aqueous media allowed significantly decreasing of the
      crystallization temperature of nanoparticles, and the single-phased crystalline
      product was formed in one stage. Morphology and properties of nanoparticles
      depended on the method and conditions of the synthesis. The heating efficiency
      directly depended on the change in the magnetic parameters of nanoparticles,
      especially on the magnetization. Performed studies showed that each of these
      methods of synthesis can be used to obtain weakly agglomerated manganite
      nanoparticles; however, particles synthesized via sol-gel method are more
      promising for use as hyperthermia inducers.PACS: 61.46.Df 75.75.Cd 81.20. Fw.

PMID- 29327155
TI  - Downregulation of miR-503 contributes to the development of drug resistance in
      ovarian cancer by targeting PI3K p85.
AB  - OBJECTIVE: Cisplatin is an important chemotherapeutic agent frequently used in
      the treatment of ovarian cancer. However, resistance to cisplatin is an obstacle
      to the treatment of ovarian cancer. Recently, many studies have demonstrated that
      microRNAs (miRNAs) are involved in the drug resistance of ovarian cancer cells.
      In this study, we explored the role of miR-503 in cisplatin-resistant ovarian
      cancer. MATERIALS AND METHODS: To investigate the relationship between miR-503
      expression and the sensitivity of ovarian cancer cells to cisplatin, the cells
      were transfected with miR-503 mimics/inhibitors. The relative expression of miR
      503 RNA and its targeted gene PI3K mRNA were detected by real-time PCR (RT-PCR).
      Western blot was used to measure relevant protein levels. Flow cytometry and CCK
      8 assay were used to analyze cell proliferation and apoptosis. RESULTS: MiR-503
      expression was significantly downregulated in cisplatin-resistant ovarian cancer
      cell line SKOV3/DDP compared with parental SKOV3. Over-expression and knock-down
      of miR-503 partially regulated apoptotic activity and changed the cisplatin
      resistance of ovarian cancer cells. In exploring the underlying mechanisms of miR
      503 in ovarian cancer cells' resistance to cisplatin, we found that miR-503 can
      directly target PI3K p85 and participates in the regulation of the PI3K/Akt
      signaling pathway. In vivo, miR-503 agomirs combined with cisplatin treatment
      significantly reduced the growth of tumors compared with cisplatin alone.
      CONCLUSIONS: Our data suggest that miR-503 might be a sensitizer to cisplatin
      treatment in ovarian cancer by targeting PI3K p85, thus giving a new insight into
      developing therapeutic strategies to overcome cisplatin resistance in ovarian
      cancer.

PMID- 29327156
TI  - Effectiveness of celecoxib for pain relief and antipyresis in second trimester
      medical abortions with misoprostol: a randomized controlled trial.
AB  - PURPOSE: To evaluate the effectiveness of celecoxib for pain relief and
      antipyresis during second trimester abortion using sublingual misoprostol.
      METHODS: Fifty-six pregnant women of gestational age 14-24 weeks were randomly
      assigned in a double-blind randomized controlled trial to receive 400 mg of
      celecoxib or placebo just before sublingual administration of misoprostol 400 ug
      every 6 h. Pain and body temperature (BT) were assessed every 1 h until the
      abortion or 24 h after the first dose of misoprostol. Pain was assessed using a
      10-cm Visual Analog Scale (VAS). BT was measured with an infrared thermometer.
      RESULTS: From January 2016 through September 2016, 28 patients were randomized
      into each study group. The mean VAS pain score at the completion of the abortion
      in the celecoxib group was significantly lower than in the placebo group (4.6 +/-
      2.8 vs. 7.3 +/- 2.2) (p = 0.012). But 42.9% of patients in both groups
      experienced severe pain and needed equivalent amounts of morphine rescue. The
      overall mean BT in the celecoxib group was significantly lower than in the
      placebo group [- 0.09 (SD = 0.04)] (p = 0.017). The mean BTs at 1, 2 and 6 h
      after each repeated dose of misoprostol in the celecoxib group were also
      significantly lower than in the placebo group. CONCLUSIONS: Single-dose 400 mg
      celecoxib had an inadequate beneficial effect on pain relief but significant
      antipyretic effect during second trimester abortions using sublingual
      misoprostol.

PMID- 29327157
TI  - Clinicopathological and prognostic significance of blood microvessel density in
      endometrial cancer: a meta-analysis and subgroup analysis.
AB  - OBJECTIVE: The study aimed to systematically review the association between
      angiogenesis and clinicopathological characteristics and its prognostic value in
      patients with endometrial cancer. METHODS: Eligible studies were searched in
      PubMed, Embase, China National Knowledge Infrastructure, and Wanfang database.
      Studies that assessed blood microvessel density (BMVD) and correlated with
      clinicopathological features and/or overall survival (OS) were included.
      Geometric mean values and hazard ratio with 95% confidence interval were pooled
      to examine the risk or hazard association. Subgroup analyses were conducted based
      on populations, BMVD criteria, BMVD markers, and type of survival analysis.
      RESULTS: A total of 29 studies of 2517 patients were included. BMVD was
      associated with depth of myometrial invasion (MI) [standard mean difference (SMD)
      1.24; 95% CI 0.53-1.95; P = 0.0006], lymphovascular space invasion (LVSI) (SMD
      0.75; 95% CI 0.3-1.21; P = 0.001), and lymph node metastasis (LNM) (SMD 0.99; 95%
      CI 0.46-1.52; P = 0.0003). BMVD was also significantly associated with poor OS
      (HR 2.65; 95% CI 1.86-3.77; P < 0.00001). The association remained significant in
      the subgroups Asian population, BMVD criteria using Weidner method, BMVD marker
      CD34 for MI, LVSI, and LNM, CD105 for MI, and factor VIII for MI and LNM,
      respectively. For OS, either Asian or non-Asian population, BMVD criteria using
      Weidner or non-Weidner method, BMVD marker CD31, or factor VIII antibody and
      analysis using univariate or multivariate were all significantly associated.
      CONCLUSIONS: BMVD was associated with deeper MI, positive LVSI, positive LNM, and
      poor OS in patients with endometrial cancer. Therefore, angiogenesis is a useful
      measure for poor clinicopathological outcomes and prognosis in patients with
      endometrial cancer.

PMID- 29327158
TI  - Comparison of Warfarin Requirements in Post-cardiac Surgery Patients: Valve
      Replacement Versus Non-valve Replacement.
AB  - INTRODUCTION: Anticoagulation with warfarin affects approximately 140,000 post
      cardiac surgery patients every year, yet there remains limited published data in
      this patient population. Dosing remains highly variable due to intrinsic risk
      factors that plague cardiac surgery candidates and a lack of diverse literature
      that can be applied to those who have undergone a cardiac surgery alternative to
      heart valve replacement (HVR). In the present study, our aim was to compare the
      warfarin requirements between HVR and non-HVR patients. METHODS: This was a
      single-center, retrospective study of post-cardiac surgery patients initiated on
      warfarin at Mayo Clinic Hospital, Rochester, from January 1st, 2013 to October
      31st, 2016. The primary outcome was the maintenance warfarin dose at the earliest
      of discharge or warfarin day 10 between patients with HVR and non-HVR cardiac
      surgeries. RESULTS: A total of 683 patients were assessed during the study
      period: 408 in the HVR group and 275 in the non-HVR group. The mean warfarin
      maintenance doses in the HVR and non-HVR groups were 2.55 mg [standard deviation
      (SD) 1.52] and 2.43 mg (SD 1.21), respectively (adjusted p = 0.65). A
      multivariable analysis was performed to adjust for gender, age, body mass index
      and drug interactions. CONCLUSIONS: This was the largest study to evaluate
      warfarin dose requirements in post-cardiac surgery patients and is the first to
      compare warfarin requirements between HVR and non-HVR patients during the
      immediate post-operative period. Both groups had similar warfarin requirements,
      which supports expanding the initial warfarin dosing recommendations of the 9th
      edition Chest guideline to include non-HVR patients as well as HVR patients.

PMID- 29327159
TI  - Efficacy and safety of third-line molecular-targeted therapy in metastatic renal
      cell carcinoma resistant to first-line vascular endothelial growth factor
      receptor tyrosine kinase inhibitor and second-line therapy.
AB  - BACKGROUND: The number of studies evaluating the efficacy and safety of third
      line molecular-targeted therapy for metastatic renal cell carcinoma (mRCC) is
      limited. METHODS: The data for 48 patients with disease progression after first
      line vascular endothelial growth factor receptor tyrosine kinase inhibitor (TKI)
      and second-line targeted therapy were evaluated. Patients with prior cytokine
      therapy were excluded. Overall survival (OS) after first- and second-line therapy
      initiation was compared between patients with and without third-line therapy. In
      addition, dose-limiting toxicities (DLTs) were evaluated. RESULTS: Twenty-two of
      48 patients (45.8%) received third-line therapy, and TKI and mammalian target of
      rapamycin inhibitor were each administered in 11 patients (50%). Patients with
      third-line therapy had significantly longer median OS after first-line therapy
      (26.6 vs. 14.6 months, p = 0.0010) and second-line therapy (18.2 vs. 7.4 months,
      p < 0.0001) compared to those without third-line therapy. Multivariate analysis
      showed that the use of third-line therapy following second-line therapy was an
      independent prognosticator for longer OS (hazard ratio 0.29, 95% confidence
      interval 0.14-0.58, p = 0.0005). The median progression-free survival and OS
      after third-line therapy was 2.76 and 8.71 months, respectively. Although a high
      frequency of DLTs was observed (n = 10, 45.5%), the frequencies were similar
      among the sequential therapies. CONCLUSIONS: Third-line therapy has a beneficial
      therapeutic effect in patients with mRCC that is resistant to previous therapies.
      However, there is a need to evaluate in detail the high frequency of adverse
      events, including DLTs.

PMID- 29327160
TI  - Differences in histological features and PD-L1 expression between sporadic
      microsatellite instability and Lynch-syndrome-associated disease in Japanese
      patients with colorectal cancer.
AB  - BACKGROUND: The field of immunotherapy has recently focused on cancers with
      microsatellite instability (MSI). These cancers include both Lynch-syndrome
      associated tumors, which are caused by mismatch repair (MMR) germline mutations,
      and sporadic MSI tumors, which are mainly attributed to MLH1 promoter
      methylation. The present study aimed to clarify differences in the histological
      and PD-L1 expression profiles between these two types of MSI cancers in Japanese
      patients. METHODS: Among 908 cases of colorectal cancer treated via surgical
      resection from 2008 to 2014, we identified 64 MSI cancers, including 36 sporadic
      MSI and 28 Lynch-syndrome-associated cancers, using a BRAF V600E mutation
      analysis and MLH1 methylation analysis. Of the latter subgroup, 21 (75%) harbored
      MMR germline mutations. RESULTS: The following were more frequent with sporadic
      MSI than with Lynch syndrome associated cancers: poor differentiation (50.0 vs.
      7.1%, P = 0.0002), especially solid type (30.6 vs. 3.6%, P = 0.0061); medullary
      morphology (19.4 and 0%, P = 0.015), Crohn-like lymphoid reaction (50.0 vs.
      25.0%, P = 0.042), and PD-L1 expression (25.0 vs. 3.6%, P = 0.034). However, the
      groups did not differ in terms of the mean invasive front and intratumoral CD8
      positive cell densities. In a logistic regression analysis, PD-L1 expression
      correlated with poor differentiation (odds ratio: 7.65, 95% confidence interval:
      1.55-37.7, P = 0.012), but not with the difference between sporadic MSI cancer
      and Lynch-syndrome-associated cancer (odds ratio: 4.74, 95% confidence interval:
      0.50-45.0, P = 0.176). CONCLUSIONS: Therefore, compared with Lynch-syndrome
      associated cancers, sporadic MSI cancers are more frequently solid, poorly
      differentiated medullary cancers that express PD-L1.

PMID- 29327161
TI  - Effects of channel blocking on information transmission and energy efficiency in
      squid giant axons.
AB  - Action potentials are the information carriers of neural systems. The generation
      of action potentials involves the cooperative opening and closing of sodium and
      potassium channels. This process is metabolically expensive because the ions
      flowing through open channels need to be restored to maintain concentration
      gradients of these ions. Toxins like tetraethylammonium can block working ion
      channels, thus affecting the function and energy cost of neurons. In this paper,
      by computer simulation of the Hodgkin-Huxley neuron model, we studied the effects
      of channel blocking with toxins on the information transmission and energy
      efficiency in squid giant axons. We found that gradually blocking sodium channels
      will sequentially maximize the information transmission and energy efficiency of
      the axons, whereas moderate blocking of potassium channels will have little
      impact on the information transmission and will decrease the energy efficiency.
      Heavy blocking of potassium channels will cause self-sustained oscillation of
      membrane potentials. Simultaneously blocking sodium and potassium channels with
      the same ratio increases both information transmission and energy efficiency. Our
      results are in line with previous studies suggesting that information processing
      capacity and energy efficiency can be maximized by regulating the number of
      active ion channels, and this indicates a viable avenue for future
      experimentation.

PMID- 29327162
TI  - Explication of a Behavioral Health-Primary Care Integration Learning
      Collaborative and Its Quality Improvement Implications.
AB  - In an effort to tackle fragmented care in the US healthcare delivery system, we
      explored the use of learning collaborative (LC) to advance integration of
      behavioral health and primary care as one of the potential solutions to a
      holistic approach to the delivery of quality healthcare to individuals with
      physical and mental illness. How a diverse group of primary care and behavioral
      health providers formed a Community of Practice (CoP) with a common purpose and
      shared vision to advance integrated care using a LC approach is described. An
      account of their learning experience, key components of their quality
      improvement, practice changes, clinical processes, and improved outcomes are
      explained. This paper aims at describing the history, creative design, processes,
      roles of the CoP and impact of the LC on the advancement of integrated care
      practice and quality improvements for further exploration and replications.

PMID- 29327163
TI  - Manipulating the Phytic Acid Content of Rice Grain Toward Improving Micronutrient
      Bioavailability.
AB  - Myo-inositol hexaphosphate, also known as phytic acid (PA), is the most abundant
      storage form of phosphorus in seeds. PA acts as a strong chelator of metal
      cations to form phytate and is considered an anti-nutrient as it reduces the
      bioavailability of important micronutrients. Although the major nutrient source
      for more than one-half of the global population, rice is a poor source of
      essential micronutrients. Therefore, biofortification and reducing the PA content
      of rice have arisen as new strategies for increasing micronutrient
      bioavailability in rice. Furthermore, global climate change effects, particularly
      rising atmospheric carbon dioxide concentration, are expected to increase the PA
      content and reduce the concentrations of most of the essential micronutrients in
      rice grain. Several genes involved in PA biosynthesis have been identified and
      characterized in rice. Proper understanding of the genes related to PA
      accumulation during seed development and creating the means to suppress the
      expression of these genes should provide a foundation for manipulating the PA
      content in rice grain. Low-PA rice mutants have been developed that have a
      significantly lower grain PA content, but these mutants also had reduced yields
      and poor agronomic performance, traits that challenge their effective use in
      breeding programs. Nevertheless, transgenic technology has been effective in
      developing low-PA rice without hampering plant growth or seed development.
      Moreover, manipulating the micronutrient distribution in rice grain, enhancing
      micronutrient levels and reducing the PA content in endosperm are possible
      strategies for increasing mineral bioavailability. Therefore, a holistic breeding
      approach is essential for developing successful low-PA rice lines. In this
      review, we focus on the key determinants for PA concentration in rice grain and
      discuss the possible molecular methods and approaches for manipulating the PA
      content to increase micronutrient bioavailability.

PMID- 29327164
TI  - Incremental predictive value of carotid arterial strain in patients with stroke.
AB  - Although increased carotid intima-media thickness (IMT) is a well-known risk
      factor for stroke, carotid IMT alone is not sufficient for risk stratification.
      The assessment of arterial properties using velocity vector imaging (VVI)
      represents a new method for quantifying structural changes. We sought to
      investigate the characteristics and the clinical value of carotid arterial
      mechanics using VVI in patients with stroke. Fifty male patients (55 +/- 5 years)
      with stroke, 30 healthy age-matched volunteers (54 +/- 8 years), and 30 healthy
      young male volunteers (29 +/- 5 years) were evaluated. The peak circumferential
      strain, strain rate, and the standard deviation of the time to peak strain and
      strain rate, representing the synchronicity of the arterial expansion, were
      analyzed using VVI of the left common carotid artery. The circumferential strain
      and strain rate significantly decreased with age, and patients with stroke showed
      the lowest degree of strain and strain rate compared with healthy age-matched
      volunteers. In addition, patients with stroke showed decreased strain and strain
      rate even in participants with a normal carotid IMT (< 0.8 mm). Although carotid
      IMT did not improve the incremental predictive value of stroke over that of
      multiple clinical risk factors (diabetes mellitus, hypertension, coronary artery
      disease, smoking), adding carotid arterial strain and strain rate provided an
      incremental predictive value over both multiple risk factors and carotid IMT for
      stroke. Along with assessment of conventional risk factors, VVI analysis could
      provide improved risk stratification for stroke.

PMID- 29327165
TI  - Measurement of cardiac valve and aortic blood flow velocities in stroke patients:
      a comparison of 4D flow MRI and echocardiography.
AB  - 4D flow MRI is an emerging technique that allows quantification of 3D blood flow
      in vivo. However, comparisons with methods of blood velocity quantification used
      in clinical routine are sparse. Therefore, we compared velocity quantification
      using 4D flow MRI with transthoracic and transesophageal echocardiography at the
      mitral and aortic valves and the aorta. Forty-eight stroke patients (age 67.3 +/-
      15.0 years) were examined by 4D flow MRI. Blood flow velocities were assessed
      using standardized 2D analysis planes positioned in the mitral valve (MV), aortic
      valve (AV), ascending aorta (AAo), and descending aorta (DAo) and were compared
      with echocardiography. MRI showed moderate-high correlations of systolic velocity
      values for the MV (r = 0.67, p < 0.001), AV (r = 0.77, p < 0.001), AAo (r = 0.93,
      p < 0.001), and DAo (r = 0.76, p < 0.001) along with moderate-high intraclass
      correlation-coefficients: MV 0.79 (95% CI 0.62, 0.88), AV 0.86 (95% CI 0.75,
      0.92), AAo 0.96 (95% CI 0.93, 0.98), and DAo 0.83 (95% CI 0.70, 0.90). However,
      MRI underestimated absolute systolic blood flow velocities compared with
      echocardiography by 8.6% for the MV (p = 0.07), 3.1% for the AV (p = 0.48), 10.7%
      for the AAo (p = 0.09), and 15.0% for the DAo (p = 0.01). Blood flow velocities
      obtained using 4D flow MRI and echocardiography at the MV, AV, and the ascending
      and DAo showed moderate to high correlations. Underestimation of absolute
      velocity values by MRI was low. Thus, 4D flow MRI seems ideally suited to
      comprehensively assess cardiac and aortic pathologies and related hemodynamic
      changes in future studies.

PMID- 29327166
TI  - Loneliness in psychosis: a systematic review.
AB  - PURPOSE: The aim of the review is to understand the relationships between
      loneliness and related psychological and social factors in individuals with
      psychosis. Loneliness is poorly understood in people with psychosis. Given the
      myriad of social challenges facing individuals with psychosis, these findings can
      inform psychosocial interventions that specifically target loneliness in this
      vulnerable group. METHODS: We adhered to the PRISMA guidelines and systematically
      reviewed empirical studies that measured loneliness either as a main outcome or
      as an associated variable in individuals with psychosis. RESULTS: A total of ten
      studies examining loneliness in people diagnosed with a psychotic disorder were
      examined. Heterogeneity in the assessment of loneliness was found, and there were
      contradictory findings on the relationship between loneliness and psychotic
      symptomatology. In individuals with psychosis, loneliness may be influenced by
      psychological and social factors such as increased depression, psychosis, and
      anxiety, poor social support, poor quality of life, more severe internalised
      stigma and perceived discrimination, and low self-esteem. CONCLUSIONS: The
      relationship between loneliness and psychosis remains poorly understood due to a
      lack of rigorous studies. Although having strong social relationships is crucial
      to facilitate recovery from serious mental illness, psychosocial interventions
      that specifically target loneliness in individuals with psychosis are lacking and
      sorely needed. Interventions targeting loneliness in those with psychosis will
      also need to account for additional barriers associated with psychosis (e.g.,
      social skill deficits, impoverished social networks, and negative symptoms).

PMID- 29327167
TI  - Does laparoscopic intracorporeal ileocolic anastomosis decreases surgical site
      infection rate? A propensity score-matched cohort study.
AB  - AIM: Foreshortened mesentery or thick abdominal wall constitutes a rationale for
      laparoscopic intracorporeal ileocolic anastomoses (ICA). The aim of this study
      was to compare intracorporeal to extracorporeal ICA in terms of surgical site
      infections in patients with Crohn's ileitis and overweight patients with right
      colon tumors. METHOD: This was a prospective propensity score-matched cohort
      study enrolling consecutive patients with Crohn's terminal ileitis and overweight
      patients with right colon tumors undergoing elective laparoscopic right colon
      resection with intracorporeal or extracorporeal ICA. Propensity score matching
      with a 1:1 ratio was employed to compare diagnosis-matched patients for age, BMI,
      ASA, and previous abdominal surgery. RESULTS: Overall, 453 patients were
      enrolled: 233 intracorporeal vs. 220 extracorporeal. Propensity score matching
      left 195 intracorporeal and 195 extracorporeal patients comparable for age (p =
      0.294), gender (p = 0.683), ASA (p = 0.545), BMI (p = 0.079), previous abdominal
      surgery (p = 0.348), and diagnosis (p = 0.301). Conversion rates (5.1 vs. 3.6%; p
      = 0.457) and intraoperative complications (1 vs. 2.1%; p = 0.45) were similar.
      Overall morbidity (5.1 vs. 12.8%; p = 0.008) and re-intervention rates (3.1 vs.
      8.7%; p = 0.029) were significantly higher in extracorporeal patients.
      Anastomotic leak rates (0.5 vs. 1.5%; p = 0.623) did not differ. Incisional SSI
      rate was significantly higher in extracorporeal patients (p = 0.01). CONCLUSION:
      Laparoscopic intracorporeal ICA reduced incisional SSI rates as compared to its
      extracorporeal counterpart.

PMID- 29327168
TI  - Social Media Social Comparison of Ability (but not Opinion) Predicts Lower
      Identity Clarity: Identity Processing Style as a Mediator.
AB  - Social comparison on social media has received increasing attention, but most
      research has focused on one type of social comparison and its psycho-emotional
      implications. Little is known about how different types of social comparison
      influence youth's identity development. Drawing on the theories of identity
      processing styles and social comparison, we examined how two different forms of
      social comparison on social media related to three identity processing styles,
      which in turn predicted youth's global self-esteem and identity clarity. We
      surveyed 219 college freshmen (Mage = 18.29; 74% female) once in the Fall and
      once in the Spring. Social comparison of ability on social media was related to
      concurrent diffuse-avoidant identity processing style, which predicted lower
      identity clarity months later. In contrast, social comparison of opinion on
      social media did not influence college freshmen's global self-esteem and identity
      clarity through identity processing styles. The findings clarified the
      implications of online social comparison for youth's identity development.

PMID- 29327169
TI  - Passive stiffness of monoarticular lower leg muscles is influenced by knee joint
      angle.
AB  - PURPOSE: While several studies demonstrated the occurrence of intermuscular
      mechanical interactions, the physiological significance of these interactions
      remains a matter of debate. The purpose of this study was to quantify the
      localized changes in the shear modulus of the gastrocnemius lateralis (GL),
      monoarticular dorsi- and plantar-flexor muscles induced by a change in knee
      angle. METHOD: Participants underwent slow passive ankle rotations at the
      following two knee positions: knee flexed at 90 degrees  and knee fully extended.
      Ultrasound shear wave elastography was used to assess the muscle shear modulus of
      the GL, soleus [both proximally (SOL-proximal) and distally (SOL distal)],
      peroneus longus (PERL), and tibialis anterior (TA). This was performed during two
      experimental sessions (experiment I: n = 11; experiment II: n = 10). The shear
      modulus of each muscle was compared between the two knee positions. RESULTS: The
      shear modulus was significantly higher when the knee was fully extended than when
      the knee was flexed (P < 0.001) for the GL (averaged increase on the whole range
      of motion: + 5.8 +/- 1.3 kPa), SOL distal (+ 4.5 +/- 1.5 kPa), PERL (+ 1.1 +/-
      0.7 kPa), and TA (+ 1.6 +/- 1.0 kPa). In contrast, a lower SOL-proximal shear
      modulus (P < 0.001, - 5.9 +/- 1.0 kPa) was observed. CONCLUSION: As the muscle
      shear modulus is linearly related to passive muscle force, these results provide
      evidence of a non-negligible intermuscular mechanical interaction between the
      human lower leg muscles during passive ankle rotations. The role of these
      interactions in the production of coordinated movements requires further
      investigation.

PMID- 29327170
TI  - The effects of a single session of spinal manipulation on strength and cortical
      drive in athletes.
AB  - PURPOSE: The primary purpose of this study was to investigate whether a single
      session of spinal manipulation (SM) increases strength and cortical drive in the
      lower limb (soleus muscle) of elite Taekwondo athletes. METHODS: Soleus-evoked V
      waves, H-reflex and maximum voluntary contraction (MVC) of the plantar flexors
      were recorded from 11 elite Taekwondo athletes using a randomized controlled
      crossover design. Interventions were either SM or passive movement control.
      Outcomes were assessed at pre-intervention and at three post-intervention time
      periods (immediate post, post 30 min and post 60 min). A multifactorial repeated
      measures ANOVA was conducted to assess within and between group differences. Time
      and session were used as factors. A post hoc analysis was carried out, when an
      interactive effect was present. Significance was set at p <= 0.05. RESULTS: SM
      increased MVC force [F(3,30) = 5.95, p < 0.01], and V-waves [F(3,30) = 4.25, p =
      0.01] over time compared to the control intervention. Between group differences
      were significant for all time periods (p < 0.05) except for the post60 force
      measurements (p = 0.07). CONCLUSION: A single session of SM increased muscle
      strength and corticospinal excitability to ankle plantar flexor muscles in elite
      Taekwondo athletes. The increased MVC force lasted for 30 min and the
      corticospinal excitability increase persisted for at least 60 min.

PMID- 29327171
TI  - Efficacy of adjuvant radiotherapy in the intracranial hemangiopericytoma.
AB  - We retrospectively evaluated an efficacy of adjuvant radiotherapy (RT) in the
      intracranial hemangiopericytoma (HPC) and analyzed prognostic factors influencing
      treatment outcomes. Among 49 patients diagnosed as localized intracranial HPC
      between 1995 and 2016, 31 patients received adjuvant RT after surgery; 26 with
      fractionated RT and 5 with stereotactic radiosurgery using Gamma Knife. After
      gross total resection (GTR) (n = 32) and subtotal resection (STR) (n = 17),
      histopathological grade was confirmed to be grade II (n = 9) or grade III (n =
      40). The median follow-up period was 50 months (range 3-216 months). The local
      recurrence was defined as intracranial relapse within 15 mm and regional
      recurrence as beyond 15 mm from the margin of surgical bed. The 10-year overall
      survival (OS) and progression-free survival (PFS) were 69.9 and 34.4%,
      respectively. The 10-year local, regional, and distant failure-free rates were
      56.6, 88.2, and 73.3%, respectively. Local tumor control was better with GTR
      followed by RT than GTR alone (p = 0.056), while there was no difference in OS.
      Local tumor control and OS after STR plus RT were equivalent to those after GTR
      alone. There were no differences in distant metastasis-free survival (DMFS) among
      GTR plus RT, GTR alone, and STR plus RT. Tumor volume > 40 cm3 was associated
      with poor PFS (p = 0.024). The local tumor recurrence was reduced by adjuvant RT
      after surgery. But OS or DMFS was not improved with adjuvant RT. PFS was better
      in the tumor with small volume at diagnosis.

PMID- 29327172
TI  - Identifying candidates for gamma knife radiosurgery among elderly patients with
      brain metastases.
AB  - We investigated the outcomes of gamma knife radiosurgery (GKRS) for elderly
      patients (>= 65 years) with brain metastases, and identified survival-associated
      factors. We retrospectively analyzed data from 115 patients treated with GKRS for
      1-15 brain metastases. The median patient age was 72 years; most primary tumors
      were pulmonary (n = 83). The mean lesion volume was 2.1 +/- 4.8 mL. A mean dose
      of 19.3 Gy was delivered to the mean 63.9% isodose line. The median overall
      survival (OS) was 5.3 months (95% confidence interval [CI] 3.5-7.1). During
      follow-up (median, 5.1 months), 91 patients died of primary cancer progression
      while 1 died of unknown causes. The 6- and 12-month local control rates were 94.9
      and 88.1%, respectively. On multivariate analysis, female sex (p = 0.005, hazard
      ratio [HR] 0.533, 95% CI 0.343-0.827) and a controlled primary tumor (p < 0.001,
      HR 0.328, 95% CI 0.180-0.596) were significantly favorable prognostic factors. Of
      non-small cell lung cancer patients with EGFR mutations, 76.5% were women (p =
      0.005). The median OS of EGFR-mutant and EGFR-wildtype patients were 19.1 and 4.7
      months, respectively (p = 0.080). Brain metastases < 3 mL showed better local
      control rates after GKRS (p = 0.005). GKRS produces favorable outcomes in women
      with brain metastases who are >= 65 years and have controlled primary tumors.
      Such patients are therefore suitable candidates for GKRS.

PMID- 29327173
TI  - Personality traits, patient-centered health status and prognosis of brain tumor
      patients.
AB  - Personality traits can be related to prognosis of cancer patients. The study
      aimed to evaluate the association of big-five personality dimensions with
      emotional and cognitive health status, and prognosis of brain tumor patients. A
      total of 178 patients admitted for brain tumor surgery were evaluated for
      personality traits (Tem item Personality Inventory), depressive/anxiety symptoms
      (Hospital Anxiety and Depression Scale or HADS) and cognitive functioning (Mini
      Mental State Examination or MMSE) on admission. One-hundred and forty-three
      patients were re-evaluated (HADS and MMSE scales) at hospital discharge. Follow
      up continued until November, 2015. Thirty-five patients were diagnosed with high
      grade glioma, 15 with low-grade glioma and 128 with benign brain tumors
      (meningioma, pituitary adenoma and vestibular schwannoma). In multivariate
      regression analyses adjusted for age, gender, past brain tumor treatment,
      psychiatric histories and medication use, and education, greater TIPI
      Extroversion score was associated with greater admission MMSE score (beta =
      0.159); TIPI-Emotional stability score, with lower HADS-Depression and HADS
      Anxiety scores on admission (beta = - 0.407 and beta = - 0.404, respectively) and
      at discharge (beta = - 0.404 and beta = - 0.319, respectively); and greater TIPI
      Openness score, with lower admission HADS-D score (beta = - 0.255, p = 0.001). In
      benign brain tumor patients, greater TIPI-Openness score was associated with
      reduced mortality risk [HR = 0.554 95% CI (0.376-0.814) p = 0.003)] independently
      from age, gender and histological diagnosis. Personality traits were not
      associated with survival of high-grade and low-grade glioma patients. Emotional
      stability and openness are associated with lower depressive/anxiety symptom
      severity, and extroversion with better cognitive functioning independently from
      demographic and clinical risk factors. Openness predicts lower mortality risk of
      low-grade/benign brain tumor patients.

PMID- 29327174
TI  - Localized targeted antiangiogenic drug delivery for glioblastoma.
AB  - Systemic delivery of antiangiogenic agents has been ineffective in improving the
      overall survival of patients with both primary and recurrent glioblastoma, in
      part due to dose-limiting toxicities. With the development of new and efficient
      localized delivery methods and vehicles, an otherwise lethal dose of
      antiangiogenic chemotherapy can be used to treat tumors while minimizing systemic
      side effects. Current in-vitro and in-vivo animal studies have shown promising
      results that encourage the pursuit towards human clinical trials for localized
      antiangiogenic treatment in the near future.

PMID- 29327175
TI  - MicroRNA-30c as a novel diagnostic biomarker for primary and secondary B-cell
      lymphoma of the CNS.
AB  - Primary lymphomas of the central nervous system (PCNSL) are highly aggressive
      tumors affecting exclusively the CNS, meninges, and eyes. PCNSL must be separated
      from secondary spread of systemic lymphoma to the CNS (SCNSL), which may occur at
      diagnosis or relapse of systemic lymphomas. At present, there are no valid
      methods to distinguish PCNSL from SCNSL based on tumor biopsy because of similar
      histological presentation. However, SCNSL and PCNSL are different in terms of
      prognosis and adequate therapy protocols. MicroRNA expression profiles of CSF
      samples collected from SCNSL and PCNSL patients were compared using microRNA
      arrays. MiR-30c revealed the largest differential expression and was selected for
      validation by RT-PCR on 61 CSF samples from patients with PCNSL and 14 samples
      from SCNSL. MiR-30c was significantly increased in patients with SCNSL compared
      to PCNSL (p < 0.001). MiR-30c levels in CSF enabled the differentiation of
      patients with PCNSL from SCNSL with an area under the curve (AUC) of 0.86, with a
      sensitivity of 90.9% and a specificity of 85.5%. Our data suggest that miR-30c
      detected in the CSF can serve as biomarker for distinction between PCNSL and
      SCNSL. The validation in a larger cohort is needed. With respect to its function,
      miR-30c may facilitate lymphoma cells to engraft into CNS by interaction with
      CELSR3 gene that controls the function of ependymal cilia and, thus, affects the
      circulation of CSF.

PMID- 29327177
TI  - Influence of sampling frequency and load calculation methods on quantification of
      annual river nutrient and suspended solids loads.
AB  - Better management of water quality in streams, rivers and lakes requires precise
      and accurate estimates of different contaminant loads. We assessed four sampling
      frequencies (2 days, weekly, fortnightly and monthly) and five load calculation
      methods (global mean (GM), rating curve (RC), ratio estimator (RE), flow
      stratified (FS) and flow-weighted (FW)) to quantify loads of nitrate-nitrogen
      (NO3--N), soluble inorganic nitrogen (SIN), total nitrogen (TN), dissolved
      reactive phosphorus (DRP), total phosphorus (TP) and total suspended solids
      (TSS), in the Manawatu River, New Zealand. The estimated annual river loads were
      compared to the reference 'true' loads, calculated using daily measurements of
      flow and water quality from May 2010 to April 2011, to quantify bias (i.e.
      accuracy) and root mean square error 'RMSE' (i.e. accuracy and precision). The GM
      method resulted into relatively higher RMSE values and a consistent negative bias
      (i.e. underestimation) in estimates of annual river loads across all sampling
      frequencies. The RC method resulted in the lowest RMSE for TN, TP and TSS at
      monthly sampling frequency. Yet, RC highly overestimated the loads for parameters
      that showed dilution effect such as NO3--N and SIN. The FW and RE methods gave
      similar results, and there was no essential improvement in using RE over FW. In
      general, FW and RE performed better than FS in terms of bias, but FS performed
      slightly better than FW and RE in terms of RMSE for most of the water quality
      parameters (DRP, TP, TN and TSS) using a monthly sampling frequency. We found no
      significant decrease in RMSE values for estimates of NO3-N, SIN, TN and DRP loads
      when the sampling frequency was increased from monthly to fortnightly. The bias
      and RMSE values in estimates of TP and TSS loads (estimated by FW, RE and FS),
      however, showed a significant decrease in the case of weekly or 2-day sampling.
      This suggests potential for a higher sampling frequency during flow peaks for
      more precise and accurate estimates of annual river loads for TP and TSS, in the
      study river and other similar conditions.

PMID- 29327176
TI  - How to Use a Graft in Irreparable Rotator Cuff Tears: A Literature Review Update
      of Interposition and Superior Capsule Reconstruction Techniques.
AB  - PURPOSE OF REVIEW: To introduce the challenges in addressing irreparable rotator
      cuff tears and examine the surgical options, specifically interposition grafting
      and superior capsule reconstruction. RECENT FINDINGS: Interposition grafting of
      rotator cuff tears shows promising results in reducing pain and improving
      function postoperatively and one study demonstrated that it performs
      significantly better than partial repair alone. Superior capsule reconstruction
      has become popular rapidly, but given the novelty of the procedure, there is
      currently a paucity of outcomes data to review. Irreparable rotator cuff tears
      are a challenging condition with a variety of surgical options available. Two
      such options-interposition and superior capsule reconstruction-both employ grafts
      in an attempt to restore joint stability and function. In the past 3 years,
      literature discussing interposition grafting has explored the different types of
      grafts, and mostly employed pre-post analysis. The recent superior capsule
      reconstruction articles strictly used human dermal allograft and offer a variety
      of surgical techniques without quantitative data.

PMID- 29327178
TI  - Clinical Impact and Risk Factors for Skeletal Muscle Loss After Complete
      Resection of Early Non-small Cell Lung Cancer.
AB  - BACKGROUND: A relationship between sarcopenia diagnosed by skeletal muscle area
      (SMA) and poor prognosis in cancer patients has recently been reported. This
      study aimed to clarify the clinical significance of postoperatively decreased SMA
      in patients with early non-small cell lung cancer (NSCLC). METHODS: This study
      selected 101 patients with pathologic stage 1 NSCLC who had undergone pre- and
      postoperative (~ 1 year) computed tomography scans and lobectomy between 2005 and
      2010 at Kyushu University Hospital. The post/pre ratio was defined as the
      postoperative normalized SMA (cm2/m2) at the 12th thoracic vertebra level divided
      by the preoperative normalized SMA. The cutoff value for the post/pre ratio was
      set at 0.9. RESULTS: The study classified 31 patients (30.7%) as having decreased
      SMA. Poor performance status (PS) was significantly associated with decreased SMA
      (p = 0.048). The patients with decreased SMA had a significantly shorter disease
      free survival (DFS) (p < 0.001) and overall survival (OS) (p < 0.001) than the
      other patients. Decreased SMA was found to be an independent prognostic factor
      for DFS (p = 0.010) and OS (p = 0.0072). The independent risk factors for
      skeletal muscle loss included poor PS (PS >= 1) and obstructive ventilatory
      impairment [forced expiratory volume (FEV) 1% < 70%]. CONCLUSIONS: Skeletal
      muscle loss after surgery is significantly associated with postoperative poor
      outcomes for patients with early NSCLC. Patients with poor PS, obstructive
      ventilatory impairment, or both need careful support to maintain their skeletal
      muscle mass. Future prospective studies may clarify whether physical activity and
      nutritional support improve postoperative prognosis.

PMID- 29327179
TI  - Liver Transplantation is Equally Effective as a Salvage Therapy for Patients with
      Hepatocellular Carcinoma Recurrence Following Radiofrequency Ablation or Liver
      Resection with Curative Intent.
AB  - BACKGROUND: Liver resection (LR) and radiofrequency ablation (RFA) are curative
      intent therapies for early stages of hepatocellular carcinoma (HCC). If HCC
      recurs, salvage liver transplant (SLT) may constitute a treatment option.
      OBJECTIVE: We aimed to compare the outcomes of patients transplanted for
      recurrent HCC after curative-intent therapies with those transplanted as initial
      therapy. METHODS: We conducted a matched-control (1:1) cohort study comparing
      patients with HCC treated with primary liver transplant (PLT) with SLT after HCC
      recurrence. Matching was performed according to the size and number of viable
      tumors at explant pathology following liver transplant. RESULTS: Between November
      1999 and December 2014, 687 patients with HCC were listed for transplant at our
      institution. A total of 559 patients were transplanted; 509 patients were treated
      with PLT and 50 patients were treated with SLT for HCC recurrence after primary
      treatment with LR (n = 25) or RFA (n = 25). The median length of follow-up from
      transplant was 64 months (0.5-195), and the median time from curative-intent
      treatment of HCC with RFA or LR to recurrence was 9.5 months (1-36) and 14.5
      months (3-143), respectively (p = 0.04). The matched cohort was composed of 48
      SLT patients (23 LR and 25 RFA) and 48 PLT patients. The 5-year risk of
      recurrence after LT was 22% in the PLT group versus 32% in the SLT group (p =
      0.53), while the 5-year actuarial patient survival after PLT was 69% versus 70%
      in the SLT group (p = 1). CONCLUSION: Liver transplant is an effective treatment
      for patients with HCC recurrence following RFA or LR. Outcomes are similar in
      both groups.

PMID- 29327181
TI  - Correction to: Promising Antibacterial Effects of Silver Nanoparticle-Loaded Tea
      Tree Oil Nanoemulsion: a Synergistic Combination Against Resistance Threat.
AB  - With regrets, there is an error in the name of one of the authors which has only
      been noticed after publication.

PMID- 29327180
TI  - Chemotherapy with or Without Definitive Radiation Therapy in Inoperable
      Pancreatic Cancer.
AB  - BACKGROUND: The LAP07 randomized trial calls into question the role of radiation
      therapy (RT) in the modern treatment of locally advanced pancreatic cancer
      (LAPC). However, advances in chemotherapy and RT limit application of the LAP07
      results to current clinical practice. Here we utilize the National Cancer
      Database (NCDB) to evaluate the effects of RT in patients receiving chemotherapy
      for LAPC. METHODS: Using the NCDB, patients with American Joint Committee on
      Cancer (AJCC) clinical stage T2-4, N0-1, M0 adenocarcinoma of the pancreas from
      2004 to 2014 were analyzed. Patients were stratified into chemotherapy only (CT)
      and chemoradiation (CRT) cohorts. Patients undergoing definitive RT, defined as
      at least 20 fractions or >= 5 Gy per fraction [i.e., stereotactic body radiation
      therapy (SBRT)] were included in the CRT cohort. Propensity-score matching (PSM)
      and landmark analysis were used to address selection bias and lead-time bias,
      respectively. RESULTS: 13,004 patients met inclusion criteria, of whom 7034 (54%)
      received CT and 5970 (46%) received CRT. After PSM, 5215 patients remained in
      each cohort. The CRT cohort demonstrated better overall survival (OS) compared
      with CT alone, with median and 1-year OS of 12 versus 10 months, and 50% and 41%,
      respectively (p < 0.001). On multivariable analysis, CRT was associated with
      superior OS with hazard ratio of 0.79 (95% confidence interval 0.76-0.83)
      compared with CT alone. CONCLUSIONS: In our series, addition of definitive
      radiotherapy to CT was associated with better OS when compared with CT alone in
      LAPC. Definitive radiotherapy should remain a treatment option for LAPC, but
      optimal selection criteria remain unclear.

PMID- 29327182
TI  - Changes in Iron Absorption After Roux-en-Y Gastric Bypass.
AB  - INTRODUCTION: Iron deficiency is one of the most common deficiencies that may
      occur after Roux-en-Y gastric bypass (RYGB). Little is known about the optimal
      treatment of post-RYGB iron deficiency. AIM: The aim of this study is to evaluate
      the changes in iron absorption characteristics after RYGB for two oral iron
      formulations, one presented in tablet form and one as in the form of a solution.
      METHOD: Iron absorption in 24 obese women was studied before and 1 month after
      RYGB. Twelve patients were tested with a single dose of 600 mg ferrous fumarate
      in tablet form (195 mg of elementary iron, group 1), and 12 patients received a
      single dose of 1390 mg ferrous gluconate as a solution (160 mg of elementary
      iron, group 2). Serum iron levels were measured before (T0) and every hour after
      ingestion of the supplement (T1-T9). RESULTS: Before surgery, iron absorption was
      similar for the two supplements (P = 0.71). However, RYGB was associated with a
      decrease in fumarate iron absorption (P < 0.001) but did not affect gluconate
      iron absorption (P = 0.13). Postoperative absorption of fumarate iron was
      significantly lower than gluconate iron at T1 (P < 0.05), but the overall
      difference over 9 h did not reach statistical significance (P = 0.53).
      CONCLUSION: RYGB adversely affects the absorption of ferrous fumarate tablets but
      not that of solubilized ferrous gluconate. A solubilized supplement is therefore
      preferred as the supplement of first choice after RYGB.

PMID- 29327183
TI  - Bidirectional Jejunojejunal Anastomosis Prevents Early Small Bowel Obstruction
      Due to the Kinking After Closure of the Mesenteric Defect in the Laparoscopic
      Roux-en-Y Gastric Bypass.
AB  - BACKGROUND: The closure of the mesenteric defects (CMD) in Roux-en-Y gastric
      bypass (RYGB) reduces the risk of small bowel obstruction (SBO) due to internal
      hernia but might be associated with an increased risk of early SBO triggered by
      the jejunojejunal anastomosis (JJS) kinking. The aim of this study was to assess
      how enlarging the JJS with a bidirectional linear stapling can aid in avoiding
      the risk of early SBO by kinking. MATERIALS AND METHODS: This retrospective
      cohort study concerns 1327 patients who underwent RYGB with CMD between May 2007
      and August 2016. The first 626 patients (group A) had a unidirectional JJS. The
      following 701 patients (group B) had a bidirectional side-to-side JJS and a hand
      sewn closure of the remaining defect. We compared early SBO between the two
      groups. RESULTS: Eleven (1.75%) early SBO due to the JJS kinking occurred in
      group A, whereas none occurred in group B (p = 0.0012). Thirty-nine early
      postoperative complications happened in group A versus 32 in group B (p = 0.17).
      Nine (1.2%) digestive bleedings occurred in group B versus two (0.3%) in group A
      (OR = 4.05 [0.87-18], p = 0.054). Average operating time was 81 min [37-330] in
      group A and 77 min [33-240] in group B. CONCLUSION: Enlarging the JJS with a
      bidirectional linear stapling is associated with a reduced risk of early SBO due
      to the anastomosis kinking. However, it could be related to an increased risk of
      digestive bleedings.

PMID- 29327184
TI  - Efficacy of Forced-Air Warming to Prevent Perioperative Hypothermia in Morbidly
      Obese Versus Non-obese Patients.
AB  - BACKGROUND: Hypothermia is associated with an increased postoperative morbidity
      and mortality. Forced-air warming systems are the most effective methods for its
      prevention. When using a mattress, a reduction in the area of diffusion of warm
      air by crushing due to excess weight cannot be ruled out. METHODS: We designed a
      prospective study to compare the efficacy of a forced-air warming mattress (Bair
      Hugger(r) 585) to prevent hypothermia (core temperature (CT degrees ) < 36 
      degrees C) in morbidly obese (group MO, body mass index (BMI) >= 40 kg/m2) and
      non-obese patients (group NO, BMI < 30 kg/m2). RESULTS: Twenty-six patients were
      included in group MO (84% bariatric surgery, 96% laparoscopic procedures) and 32
      in group NO (37.5% cholecystectomy, 62.5% laparoscopic procedures). The incidence
      of hypothermia was not different between the two groups 1 h after induction (H1)
      and at extubation: 22 vs 19% (not significant (NS)) and 23 vs 19% (NS) for the
      group MO versus group NO. At H1, the mean CT degrees  was not different: 36.3 +/-
      0.4  degrees C vs 36.4 +/- 0.5  degrees C (NS), group MO versus group NO. No
      patient presented severe hypothermia (CT degrees  < 34.9  degrees C). Dysfunction
      of the forced-air warming mattress was observed for eight patients (31%) in group
      MO but for none in group NO. CONCLUSION: The forced-air warming mattress is
      effective in preventing hypothermia in MO patients. However, excess weight is
      associated with frequent dysfunction of the system, which does not make it a
      practical system in a context of MO.

PMID- 29327185
TI  - Degradation of organics extracted from dewatered sludge by alkaline pretreatment
      in microbial electrolysis cell.
AB  - Waste activated sludge in China are mostly subjected to dewatering process before
      final disposal without stabilization. This study investigated the feasibility of
      organics degradation and H2 production from non-stabilized dewatered sludge (DS)
      by microbial electrolysis cells (MECs). Alkaline pretreatment was used to
      disintegrate sludge matrix and solubilize organic matters in DS. Then, the
      treatment performance of DS supernatant in a single-chamber MEC at various
      applied voltages was investigated. The COD (chemical oxygen demand) removal rate
      increased with increasing voltage, which ranged from 26.35 to 44.92% at 0.5-0.9
      V. The average coulombic efficiency was 75.6%, while the cathodic hydrogen
      recovery was not satisfied (15.56-20.05%) with H2 production rates of 0.027-0.038
      m3 H2/(m3 day). The reasons could be ascribed to the complexity of the substrate,
      H2 loss, and the confinement of configuration in scale-up. The organic matter
      degradation was influenced by the composition of DS. The carbohydrates could be
      readily used; meanwhile, the major component of the DS supernatant, i.e.
      proteins, was difficult to be utilized, which resulted from the low
      biodegradability of the transphilic fractions during the MEC operation.

PMID- 29327187
TI  - Does biochar affect the availability and chemical fractionation of phosphate in
      soils?
AB  - Biochar as a soil amendment has been reported to affect the content and
      availability of soil nutrients. In this study, we aimed to test whether the
      biochar addition to soils would change the availability and chemical
      fractionation of phosphate in soils. Two soils (Ultisol and Alfisol) were amended
      with five kinds of biochars at application rate of 0, 1, and 2% (w/w). After 3
      month incubation, availability and chemical forms of P were measured to
      investigate the potential effect and role of biochar in improving P availability
      in soils. The biochars used here had a lager variation of P content, depending on
      their feedstocks. Compared to the untreated soils, application of biochars
      derived from deciduous tree leaves (DLB), reed (RB), and rice straw (RSB)
      significantly increased the pH of two soils. The total P content of biochar
      amended soils was increased with the addition of biochars. However, only RSB
      exhibited a significant increase (p < 0.05) of total P content. Application of
      biochars significantly increased the NH4Cl-extractable P content of two soils,
      indicating that biochars were able to increase the availability of phosphate in
      soils, but the amount of available P was dependent on biochar types. Ultisol and
      Alfisol amended with RSB (2% w/w) showed an increase in the P availability (0.5 M
      NaHCO3-extractable P) by 46 and 39%, respectively. For strongly acidic Ultisol,
      addition of biochar significantly increased Al-P and Ca-P content, as well as
      decreased Fe-P content. The P desorption test indicated the release of P from
      soils increased with the addition of biochar. Results suggested that biochar
      would change the P sorption affinity of the soil and help to increase the
      availability of fixed P. The increase of P availability with biochar application
      was due to the pH change and direct P contribution from biochar. Our results
      concluded that biochar affected the availability, chemical forms, and sorption
      capability of phosphate in soil. The extent of biochar effects on soil P varied
      greatly with the type of feedstock of biochar and soil type.

PMID- 29327188
TI  - Temporal variation in bacterial and methanogenic communities of three full-scale
      anaerobic digesters treating swine wastewater.
AB  - To investigate the effects of temporal variations of process parameters on
      microbial community structures in the two types of full-scale anaerobic digester
      treating swine wastewater, three full-scale anaerobic digesters were monitored.
      An anaerobic filter (AF)-type digester located in Gong-Ju (GJ) showed the highest
      COD removal among three digesters and maintained stable efficiency. A digester in
      Hong-Seong (HS) was of the same type as it GJ and showed improved efficiency over
      the sampling period. A continuously stirred tank reactor (CSTR)-type digester in
      Soon-Cheon (SC) showed decreasing efficiency due to a high residual concentration
      of VFAs and NH4+. These process efficiencies were closely correlated to the
      Simpson indices of the methanogenic communities. Genera Bacillus, Methanosaeta,
      and Methanospirillum that have filamentous morphology were dominant in both AF
      type digesters, but genera Acholeplasma, Methanosarcina, and Methanoculleus that
      have spherical or coccoid morphology were dominantly abundant in the CSTR-type
      digester. Correlation between populations suggests a possible syntrophic
      relationship between genera Desulfobulbus and Methanosaeta in digesters GJ and
      HS.

PMID- 29327186
TI  - Environmental pollutants, pathogens and immune system in earthworms.
AB  - Earthworms also known as farmer's friends are natural tillers of soil. They
      belong to Phylum Annelida and class Oligochaeta. Acid soils with organic matter
      and surface humus maintain the largest fauna of worms and earthworms. Due to
      their habitat in soil, they are constantly exposed to microbes and pollution
      generated by anthropogenic sources. Studies have revealed that damage of the
      immune system of earthworms can lead to alterations of both morphological and
      cellular characteristics of worms, activation of signalling pathways and can
      strongly influence their survival. Therefore, the understanding of the robust
      immune system in earthworms has become very important from the point of view of
      understanding its role in combating pathogens and pollutants and its role in
      indicating the soil pollution. In this article, we have outlined the (i)
      components of the immune system and (ii) their function of immunological
      responses on exposure to pollutants and pathogens. This study finds importance
      from the point of view of ecotoxicology and monitoring of earthworm health and
      exploring the scope of earthworm immune system components as biomarkers of
      pollutants and environmental toxicity. The future scope of this review remains in
      understanding the earthworm immunobiology and indicating strong biomarkers for
      pollution.

PMID- 29327189
TI  - Using a high-organic matter biowall to treat a trichloroethylene plume at the
      Beaver Dam Road landfill.
AB  - Trichloroethylene (TCE) is a highly effective industrial degreasing agent and
      known carcinogen. It was frequently buried improperly in landfills and has
      subsequently become one of the most common groundwater and soil contaminants in
      the USA. A common strategy to remediate TCE-contaminated sites and to prevent
      movement of the TCE plumes into waterways is to construct biowalls which consist
      of biomaterials and amendments to enhance biodegradation. This approach was
      chosen to contain a TCE plume emanating from a closed landfill in Maryland.
      However, predicting the effectiveness of biowalls is often site specific.
      Therefore, we conducted an extensive series of batch reactor studies at 12 
      degrees C as opposed to the typical room temperature to examine biowall fill
      material combinations including the effects of zero-valent iron (ZVI) and
      glycerol amendments. No detectable TCE was observed after several months in the
      laboratory study when using the unamended 4:3 mulch-to-compost combination. In
      the constructed biowall, this mixture reduced the upstream TCE concentration by
      approximately 90% and generated ethylene downstream, an indication of successful
      reductive dechlorination. However, the more toxic degradation product vinyl
      chloride (VC) was also detected downstream at levels approximately ten times
      greater than the maximum contaminant level. This indicates that incomplete
      degradation also occurred. In the laboratory, ZVI reduced VC formation. A hazard
      quotient was calculated for the landfill site with and without the biowall. The
      addition of the biowall decreased the hazard quotient by 88%.

PMID- 29327190
TI  - Chemical characterization and quantitativ e assessment of source-specific health
      risk of trace metals in PM1.0 at a road site of Delhi, India.
AB  - This study presents the concentration of submicron aerosol (PM1.0) collected
      during November, 2009 to March, 2010 at two road sites near the Indian Institute
      of Technology Delhi campus. In winter, PM1.0 composed 83% of PM2.5 indicating the
      dominance of combustion activity-generated particles. Principal component
      analysis (PCA) proved secondary aerosol formation as a dominant process in
      enhancing aerosol concentration at a receptor site along with biomass burning,
      vehicle exhaust, road dust, engine and tire tear wear, and secondary ammonia. The
      non-carcinogenic and excess cancer risk for adults and children were estimated
      for trace element data set available for road site and at elevated site from
      another parallel work. The decrease in average hazard quotient (HQ) for children
      and adults was estimated in following order: Mn > Cr > Ni > Pb > Zn > Cu both at
      road and elevated site. For children, the mean HQs were observed in safe level
      for Cu, Ni, Zn, and Pb; however, values exceeded safe limit for Cr and Mn at road
      site. The average highest hazard index values for children and adults were
      estimated as 22 and 10, respectively, for road site and 7 and 3 for elevated
      site. The road site average excess cancer risk (ECR) risk of Cr and Ni was close
      to tolerable limit (10-4) for adults and it was 13-16 times higher than the safe
      limit (10-6) for children. The ECR of Ni for adults and children was 102 and 14
      times higher at road site compared to elevated site. Overall, the observed ECR
      values far exceed the acceptable level.

PMID- 29327191
TI  - Iron-impregnated zeolite catalyst for efficient removal of micropollutants at
      very low concentration from Meurthe river.
AB  - In this paper, for the first time, faujasite Y zeolite impregnated with iron
      (III) was employed as a catalyst to remove a real cocktail of micropollutants
      inside real water samples from the Meurthe river by the means of the
      heterogeneous photo-Fenton process. The catalyst was prepared by the wet
      impregnation method using iron (III) nitrate nonahydrate as iron precursor.
      First, an optimization of the process parameters was conducted using phenol as
      model macro-pollutant. The hydrogen peroxide concentration, the light wavelength
      (UV and visible) and intensity, the iron loading immobilized, as well as the pH
      of the solution were investigated. Complete photo-Fenton degradation of the
      contaminant was achieved using faujasite containing 20 wt.% of iron, under UV
      light, and in the presence of 0.007 mol/L of H2O2 at pH 5.5. In a second step,
      the optimized process was used with real water samples from the Meurthe river.
      Twenty-one micropollutants (endocrine disruptors, pharmaceuticals, personal care
      products, and perfluorinated compounds) including 17 pharmaceutical compounds
      were specifically targeted, detected, and quantified. All the initial
      concentrations remained in the range of nanogram per liter (0.8-88 ng/L). The
      majority of the micropollutants had a large affinity for the surface of the iron
      impregnated faujasite. Our results emphasized the very good efficiency of the
      photo-Fenton process with a cocktail of a minimum of 21 micropollutants. Except
      for sulfamethoxazole and PFOA, the concentrations of all the other
      microcontaminants (bisphenol A, carbamazepine, carbamazepine-10,11-epoxide,
      clarithromycin, diclofenac, estrone, ibuprofen, ketoprofen, lidocaine, naproxen,
      PFOS, triclosan, etc.) became lower than the limit of quantification of the LC
      MS/MS after 30 min or 6 h of photo-Fenton treatment depending on their initial
      concentrations. The photo-Fenton degradation of PFOA can be neglected. The photo
      Fenton degradation of sulfamethoxazole obeys first-order kinetics in the presence
      of the cocktail of the other micropollutants.

PMID- 29327192
TI  - Towards a better control of the wastewater treatment process: excitation-emission
      matrix fluorescence spectroscopy of dissolved organic matter as a predictive tool
      of soluble BOD5 in influents of six Parisian wastewater treatment plants.
AB  - The online monitoring of dissolved organic matter (DOM) in raw sewage water is
      expected to better control wastewater treatment processes. Fluorescence
      spectroscopy offers one possibility for both the online and real-time monitoring
      of DOM, especially as regards the DOM biodegradability assessment. In this study,
      three-dimensional fluorescence spectroscopy combined with a parallel factor
      analysis (PARAFAC) has been investigated as a predictive tool of the soluble
      biological oxygen demand in 5 days (BOD5) for raw sewage water. Six PARAFAC
      components were highlighted in 69 raw sewage water samples: C2, C5, and C6
      related to humic-like compounds, along with C1, C3, and C4 related to protein
      like compounds. Since the PARAFAC methodology is not available for online
      monitoring, a peak-picking approach based on maximum excitation-emission (Ex-Em)
      localization of the PARAFAC components identified in this study has been used. A
      good predictive model of soluble BOD5 using fluorescence spectroscopy parameters
      was obtained (r2 = 0.846, adjusted r2 = 0.839, p < 0.0001). This model is quite
      straightforward, easy to automate, and applicable to the operational field of
      wastewater treatment for online monitoring purposes.

PMID- 29327193
TI  - Effect of vegetation type on treatment performance and bioelectric production of
      constructed wetland modules combined with microbial fuel cell (CW-MFC) treating
      synthetic wastewater.
AB  - An operation of microcosm-constructed wetland modules combined with microbial
      fuel cell device (CW-MFC) was assessed for wastewater treatment and bioelectric
      generation. One of the crucial aims of the present experiment is also to
      determine effect of vegetation on wastewater treatment process and bioelectric
      production in wetland matrix with microbial fuel cell. Accordingly, CW-MFC
      modules with vegetation had higher treatment efficiency compared to unplanted
      wetland module, and average COD, NH4+, and TP removal efficiency in vegetated
      wetland modules were ranged from 85 to 88%, 95 to 97%, and 95 to 97%,
      respectively. However, the highest NO3- removal (63%) was achieved by unplanted
      control module during the experiment period. The maximum average output voltage,
      power density, and Coulombic efficiency were obtained in wetland module vegetated
      with Typha angustifolia for 1.01 +/- 0.14 V, 7.47 +/- 13.7 mWatt/m2, and 8.28 +/-
      10.4%, respectively. The results suggest that the presence of Typha angustifolia
      vegetation in the CW-MFC matrix provides the benefits for treatment efficiency
      and bioelectric production; thus, it increases microbial activities which are
      responsible for biodegradation of organic compounds and catalyzed to electron
      flow from anode to cathode. Consequently, we suggest that engineers can use
      vegetated wetland matrix with Typha angustifolia in CW-MFC module in order to
      maximize treatment efficiency and bioelectric production.

PMID- 29327194
TI  - Agro-industrial waste recycling by Trichosporon fermentans: conversion of waste
      sweetpotato vines alone into lipid.
AB  - Agro-industrial waste can be used to replace traditional carbohydrates, such as
      sucrose, starch, and glucose in many industrial fermentation processes. This
      study investigated the conversion of pre-treated waste sweetpotato vines (SV)
      into lipid by Trichosporon fermentans under the separate hydrolysis and
      fermentation (SHF) and the simultaneous saccharification and fermentation (SSF)
      processes. The results showed that SV autoclaving significantly increased the
      lipid accumulation of T. fermentans compared with acid or alkaline hydrolysis.
      The effects of different pre-treatments on SV were also studied by scanning
      electron microscopy and Fourier transform infrared spectroscopy, which showed the
      partial removal of the aliphatic fractions, hemicelluloses, and lignin during pre
      treatment. Moreover, the lipid yield of T. fermentans in SSF was 6.98 g L-1,
      which was threefold higher than that (2.79 g L-1) in SHF, and the lipid contents
      of yeast in SSF and SHF were 36 and 25%, respectively. Overall, this study
      indicated that SSF using autoclaved SV could increase the growth and lipid
      production of T. fermentans and provided an efficient way to realize the resource
      utilization of waste SV.

PMID- 29327195
TI  - Long-term variations of the riverine input of potentially toxic dissolved
      elements and the impacts on their distribution in Jiaozhou Bay, China.
AB  - The concentrations of the potentially toxic dissolved elements (PTEs) As, Hg, Cr,
      Pb, Cd, and Cu in the main rivers into Jiaozhou Bay (JZB) during 1981-2006 were
      measured, and the impact of the fluvial PTE fluxes on their distributions in the
      bay was investigated. The overall average concentration in the rivers into JZB
      ranged from 8.8 to 39.6 MUg L-1 for As, 10.1 to 632.6 ng L-1 for Hg, 4.1 to
      3003.6 MUg L-1 for Cr, 8.5 to 141.9 MUg L-1 for Pb, 1.1 to 34.2 MUg L-1 for Cd,
      and 13.2 to 1042.8 MUg L-1 for Cu. The interannual average concentration
      variations of the PTEs in these rivers were enormous, with maximum differences of
      41-21,680 times, while their relative seasonal changes were far smaller with
      maximum differences of 3-12 times. The total annual fluvial fluxes for As, Hg,
      and Cr into JZB exhibited the inverse "U" pattern, while those for Pb and Cd
      showed the "N" pattern. As a whole, the total annual Cu flux presented a growing
      tendency from 1998 to 2006. In general, the changing trends of the PTE
      concentrations in JZB were similar to those of their annual fluxes from the
      rivers, indicating a great impact of their fluvial fluxes on their distributions
      in JZB. The annual concentration of Cd in the bay almost remained constant and
      differed from the fluvial flux of Cd. The diversified pattern of the
      environmental Kuznets curve (EKC) represented China's approach to
      industrialization as "improving while developing."

PMID- 29327196
TI  - Biochar amendment with fertilizers increases peanut N uptake, alleviates soil N2O
      emissions without affecting NH3 volatilization in field experiments.
AB  - Biochar application to soil is currently widely advocated for a variety of
      reasons related to sustainability. However, the synergistic effects of biochar
      combined with mineral or organic fertilizer on soil N2O emissions, NH3
      volatilization, and plant N uptake are poorly documented. Field plot experiments
      planted with peanut were conducted under the application of biochar (derived from
      rice husk and cottonseed husk, 50 t ha-1) with organic or mineral fertilizer. It
      was found that biochar increased soil nutrient availability and decreased surface
      soil bulk density, demonstrating that biochar could improve the soil quality
      especially in the 0-20-cm profile. The total N content of the plant changed
      little with treatments, but the kernel N concentration increased significantly
      when biochar was applied with organic fertilizer. Peanut yield increased with
      biochar amendment while no significant difference was observed in plant biomass,
      suggesting biochar had a positive effect on belowground biomass. Peanut N uptake
      was also increased following biochar amendment with either organic or mineral
      fertilizers. While biochar amendment had no significant effect on soil NH3
      volatilization, it did decrease the cumulative N2O emission by 36.3% on average
      with organic fertilizer, and by 32.6% with mineral fertilizer, respectively (p <
      0.05). The copy numbers of 16S rDNA, nifH, nirK, and nirS were not influenced by
      the application of biochar; however, the copy number of nosZ was significantly
      increased under biochar plus mineral fertilizer treatment. The results imply that
      biochar application can suppress N2O emissions, as a result of abiotic factors
      and enhanced peanut N uptake rather than changes of denitrification genes.

PMID- 29327197
TI  - [New kidney function tests: Renal functional reserve and furosemide stress test].
AB  - Acute kidney injury (AKI) occurs in 30-50% of all intensive care patients. Renal
      replacement therapy (RRT) has to be initiated in 10-15%. The early in-hospital
      mortality is about 50%. Up to 20% of all survivors develop chronic kidney disease
      after intensive care discharge and progress to end-stage kidney disease within
      the next 10 years. For timely initiation of prophylactic or therapeutic
      interventions, it is crucial to exactly determine the actual kidney function, i.
      e., glomerular filtration rate (GFR), and to gain insight into the further
      development of kidney function. Traditionally, renal function has been estimated
      using serum levels of creatinine or urea. Unfortunately, both are notoriously
      unreliable and insensitive in intensive care patients. Cystatin C has fewer non
      GFR determinants when compared to creatinine and is more sensitive and accurate
      to detect early decreases of GFR. At present, new functional tests are discussed,
      namely the furosemide stress test (FST) and renal functional reserve (RFR). The
      FST consists of an intravenous infusion of 1.0-1.5 mg/kgBW furosemide to
      critically ill patients with AKI. An increase in urine output to >100 ml/h is
      indicative of a GFR >20 ml/min and almost certainly excludes progression to AKI
      stage III and need for RRT. Estimation of RFR can be made by short-term oral or
      intravenous administration of a high protein load. A subsequent increase in GFR
      defines the presence and the magnitude of functional reserve which can be
      activated. Loss of RFR is an indicator of loss of functioning nephron mass and
      incomplete recovery following AKI. Both FST and RFR can help to improve diagnosis
      and care of high-risk patients with acute and chronic kidney disease.

PMID- 29327198
TI  - Graphene Oxide Hybridized nHAC/PLGA Scaffolds Facilitate the Proliferation of
      MC3T3-E1 Cells.
AB  - Biodegradable porous biomaterial scaffolds play a critical role in bone
      regeneration. In this study, the porous nano-hydroxyapatite/collagen/poly(lactic
      co-glycolic acid)/graphene oxide (nHAC/PLGA/GO) composite scaffolds containing
      different amount of GO were fabricated by freeze-drying method. The results show
      that the synthesized scaffolds possess a three-dimensional porous structure. GO
      slightly improves the hydrophilicity of the scaffolds and reinforces their
      mechanical strength. Young's modulus of the 1.5 wt% GO incorporated scaffold is
      greatly increased compared to the control sample. The in vitro experiments show
      that the nHAC/PLGA/GO (1.5 wt%) scaffolds significantly cell adhesion and
      proliferation of osteoblast cells (MC3T3-E1). This present study indicates that
      the nHAC/PLGA/GO scaffolds have excellent cytocompatibility and bone regeneration
      ability, thus it has high potential to be used as scaffolds in the field of bone
      tissue engineering.

PMID- 29327199
TI  - Glycogen Synthase Kinase-3beta Regulates Equilibrium Between Neurogenesis and
      Gliogenesis in Rat Model of Parkinson's Disease: a Crosstalk with Wnt and Notch
      Signaling.
AB  - Neurogenesis involves generation of functional newborn neurons from neural stem
      cells (NSCs). Insufficient formation or accelerated degeneration of newborn
      neurons may contribute to the severity of motor/nonmotor symptoms of Parkinson's
      disease (PD). However, the functional role of adult neurogenesis in PD is yet not
      explored and whether glycogen synthase kinase-3beta (GSK-3beta) affects multiple
      steps of adult neurogenesis in PD is still unknown. We investigated the possible
      underlying molecular mechanism of impaired adult neurogenesis associated with PD.
      Herein, we show that single intra-medial forebrain bundle (MFB) injection of 6
      hydroxydopamine (6-OHDA) efficiently induced long-term activation of GSK-3beta
      and reduced NSC self-renewal, proliferation, neuronal migration, and neuronal
      differentiation accompanied with increased astrogenesis in subventricular zone
      (SVZ) and hippocampal dentate gyrus (DG). Indeed, 6-OHDA also delayed maturation
      of neuroblasts in the DG as witnessed by their reduced dendritic length and
      arborization. Using a pharmacological approach to inhibit GSK-3beta activation by
      specific inhibitor SB216763, we show that GSK-3beta inhibition enhances radial
      glial cells, NSC proliferation, self-renewal in the SVZ, and the subgranular zone
      (SGZ) in the rat PD model. Pharmacological inhibition of GSK-3beta activity
      enhances neuroblast population in SVZ and SGZ and promotes migration of
      neuroblasts towards the rostral migratory stream and lesioned striatum from
      dorsal SVZ and lateral SVZ, respectively, in PD model. GSK-3beta inhibition
      enhances dendritic arborization and survival of granular neurons and stimulates
      NSC differentiation towards the neuronal phenotype in DG of PD model. The
      aforementioned effects of GSK-3beta involve a crosstalk between Wnt/beta-catenin
      and Notch signaling pathways that are known to regulate NSC dynamics.

PMID- 29327200
TI  - Exocyst Complex Member EXOC5 Is Required for Survival of Hair Cells and Spiral
      Ganglion Neurons and Maintenance of Hearing.
AB  - The exocyst, an octameric protein complex consisting of Exoc1 through Exoc8, was
      first determined to regulate exocytosis by targeting vesicles to the plasma
      membrane in yeast to mice. In addition to this fundamental role, the exocyst
      complex has been implicated in other cellular processes. In this study, we
      investigated the role of the exocyst in cochlear development and hearing by
      targeting EXOC5, a central exocyst component. Deleting Exoc5 in the otic
      epithelium with widely used Cre lines resulted in early lethality. Thus, we
      generated two different inner ear-specific Exoc5 knockout models by crossing
      Gfi1Cre mice with Exoc5f/f mice for hair cell-specific deletion
      (Gfi1Cre/+;Exoc5f/f) and by in utero delivery of rAAV-iCre into the otocyst of
      embryonic day 12.5 for deletion throughout the otic epithelium (rAAV2/1
      iCre;Exoc5f/f). Gfi1Cre/+;Exoc5f/f mice showed relatively normal hair cell
      morphology until postnatal day 20, after which hair cells underwent apoptosis
      accompanied by disorganization of stereociliary bundles, resulting in progressive
      hearing loss. rAAV2/1-iCre;Exoc5f/f mice exhibited abnormal neurite morphology,
      followed by apoptotic degeneration of spiral ganglion neurons (SGNs) and hair
      cells, which led to profound and early-onset hearing loss. These results
      demonstrate that Exoc5 is essential for the normal development and survival of
      cochlear hair cells and SGNs, as well as the functional maintenance of hearing.

PMID- 29327201
TI  - Allele-Specific Biased Expression of the CNTN6 Gene in iPS Cell-Derived Neurons
      from a Patient with Intellectual Disability and 3p26.3 Microduplication Involving
      the CNTN6 Gene.
AB  - Copy number variations (CNVs) of the human CNTN6 gene caused by megabase-scale
      microdeletions or microduplications in the 3p26.3 region are often the cause of
      neurodevelopmental disorders, including intellectual disability and developmental
      delay. Surprisingly, patients with different copy numbers of this gene display
      notable overlapping of neuropsychiatric symptoms. The complexity of the study of
      human neuropathologies is associated with the inaccessibility of brain material.
      This problem can be overcome through the use of reprogramming technologies that
      permit the generation of induced pluripotent stem (iPS) cells from fibroblasts
      and their subsequent in vitro differentiation into neurons. We obtained a set of
      iPS cell lines derived from a patient carrier of the CNTN6 gene duplication and
      from two healthy donors. All iPS cell lines displayed the characteristics of
      pluripotent cells. Some iPS cell lines derived from the patient and from healthy
      donors were differentiated in vitro by exogenous expression of the Ngn2
      transcription factor or by spontaneous neural differentiation of iPS cells
      through the neural rosette stage. The obtained neurons showed the characteristics
      of mature neurons as judged by the presence of neuronal markers and by their
      electrophysiological characteristics. Analysis of allele-specific expression of
      the CNTN6 gene in these neuronal cells by droplet digital PCR demonstrated that
      the level of expression of the duplicated allele was significantly reduced
      compared to that of the wild-type allele. Importantly, according to the
      sequencing data, both copies of the CNTN6 gene, which were approximately 1 Mb in
      size, showed no any additional structural rearrangements.

PMID- 29327202
TI  - Transient Disruption of Adenosine Signaling During Embryogenesis Triggers a Pro
      epileptic Phenotype in Adult Zebrafish.
AB  - Adenosinergic signaling has important effects on brain function, anatomy, and
      physiology in both late and early stages of development. Exposure to caffeine, a
      non-specific blocker of adenosine receptor, has been indicated as a developmental
      risk factor. Disruption of adenosinergic signaling during early stages of
      development can change the normal neural network formation and possibly lead to
      an increase in susceptibility to seizures. In this work, morpholinos (MO)
      temporarily blocked the translation of adenosine receptor transcripts, adora1,
      adora2aa, and adora2ab, during the embryonic phase of zebrafish. It was observed
      that the block of adora2aa and adora2aa + adora2ab transcripts increased the
      mortality rate and caused high rate of malformations. To test the susceptibility
      of MO adora1, MO adora2aa, MO adora2ab, and MO adora2aa + adora2ab animals to
      seizure, pentylenetetrazole (10 mM) was used as a convulsant agent in larval and
      adult stages of zebrafish development. Although no MO promoted significant
      differences in latency time to reach the seizures stages in 7-day-old larvae,
      during the adult stage, all MO animals showed a decrease in the latency time to
      reach stages III, IV, and V of seizure. These results indicated that transient
      interventions in the adenosinergic signaling through high affinity adenosine
      receptors during embryonic development promote strong outcomes on survival and
      morphology. Additionally, long-term effects on neural development can lead to
      permanent impairment on neural signaling resulting in increased susceptibility to
      seizure.

PMID- 29327203
TI  - Loss of Cx43-Mediated Functional Gap Junction Communication in Meningeal
      Fibroblasts Following Mouse Hepatitis Virus Infection.
AB  - Mouse hepatitis virus (MHV) infection causes meningoencephalitis by disrupting
      the neuro-glial and glial-pial homeostasis. Recent studies suggest that MHV
      infection alters gap junction protein connexin 43 (Cx43)-mediated intercellular
      communication in brain and primary cultured astrocytes. In addition to
      astrocytes, meningeal fibroblasts also express high levels of Cx43. Fibroblasts
      in the meninges together with the basal lamina and the astrocyte endfeet forms
      the glial limitans superficialis as part of the blood-brain barrier (BBB).
      Alteration of glial-pial gap junction intercellular communication (GJIC) in MHV
      infection has the potential to affect the integrity of BBB. Till date, it is not
      known if viral infection can modulate Cx43 expression and function in cells of
      the brain meninges and thus affect BBB permeability. In the present study, we
      have investigated the effect of MHV infection on Cx43 localization and function
      in mouse brain meningeal cells and primary meningeal fibroblasts. Our results
      show that MHV infection reduces total Cx43 levels and causes its intracellular
      retention in the perinuclear compartments reducing its surface expression.
      Reduced trafficking of Cx43 to the cell surface in MHV-infected cells is
      associated with loss functional GJIC. Together, these data suggest that MHV
      infection can directly affect expression and cellular distribution of Cx43
      resulting in loss of Cx43-mediated GJIC in meningeal fibroblasts, which may be
      associated with altered BBB function observed in acute infection.

PMID- 29327204
TI  - Neuroprotective Effects of Filgrastim in Rotenone-Induced Parkinson's Disease in
      Rats: Insights into its Anti-Inflammatory, Neurotrophic, and Antiapoptotic
      Effects.
AB  - All current treatments of Parkinson's disease (PD) focus on enhancing the
      dopaminergic effects and providing symptomatic relief; however, they cannot delay
      the disease progression. Filgrastim, a recombinant methionyl granulocyte colony
      stimulating factor, demonstrated neuroprotection in many neurodegenerative and
      neurological diseases. This study aimed to assess the neuroprotective effects of
      filgrastim in rotenone-induced rat model of PD and investigate the potential
      underlying mechanisms of filgrastim actions. The effects of two doses of
      filgrastim (20 and 40 MUg/kg) on spontaneous locomotion, catalepsy, body weight,
      histology, and striatal dopamine (DA) content, as well as tyrosine hydroxylase
      (TH) and alpha-synuclein expression, were evaluated. Then, the effective dose was
      further tested for its potential anti-inflammatory, neurotrophic, and
      antiapoptotic effects. Filgrastim (40 MUg/kg) prevented rotenone-induced motor
      deficits, weight reduction, striatal DA depletion, and histological damage.
      Besides, it significantly inhibited rotenone-induced decrease in TH expression
      and increase in alpha-synuclein immunoreactivity in the midbrains and striata of
      the rats. These effects were associated with reduction of rotenone-induced
      neuroinflammation, apoptosis, and brain-derived neurotrophic factor depletion.
      Collectively, these results suggest that filgrastim might be a good candidate for
      management of PD.

PMID- 29327205
TI  - Nociceptive Roles of TRPM2 Ion Channel in Pathologic Pain.
AB  - Pain is a protective mechanism that enables us to avoid potentially harmful
      environments. However, when pathologically persisted and aggravated under
      severely injured or inflamed conditions, pain often reduces the quality of life
      and thus is considered as a disease to eliminate. Inflammatory and/or neuropathic
      mechanisms may exaggerate interactions between damaged tissues and neural
      pathways for pain mediation. Similar mechanisms also promote the communication
      among cellular participants in synapses at spinal or higher levels, which may
      amplify nociceptive firing and subsequent signal transmission, deteriorating the
      pain sensation. In this pathology, important cellular players are afferent
      sensory neurons, peripheral immune cells, and spinal glial cells. Arising from
      damage of injury, overloaded interstitial and intracellular reactive oxygen
      species (ROS) and intracellular Ca2+ are key messengers in the development and
      maintenance of pathologic pain. Thus, an ROS-sensitive and Ca2+-permeable ion
      channel that is highly expressed in the participant cells might play a critical
      role in the pathogenesis. Transient receptor potential melastatin subtype 2
      (TRPM2) is the unique molecule that satisfies all of the requirements: the
      sensitivity, permeability, and its expressing cells. Notable progress in
      delineating the role of TRPM2 in pain has been achieved during the past decade.
      In the present review, we summarize the important findings in the key cellular
      components that are involved in pathologic pain. This overview will help to
      understand TRPM2-mediated pain mechanisms and speculate therapeutic strategies by
      utilizing this updated information.

PMID- 29327207
TI  - Phenotypic and Functional Characteristics of Human Schwann Cells as Revealed by
      Cell-Based Assays and RNA-SEQ.
AB  - This study comprehensively addresses the phenotype, function, and whole
      transcriptome of primary human and rodent Schwann cells (SCs) and highlights key
      species-specific features beyond the expected donor variability that account for
      the differential ability of human SCs to proliferate, differentiate, and interact
      with axons in vitro. Contrary to rat SCs, human SCs were insensitive to mitogenic
      factors other than neuregulin and presented phenotypic variants at various stages
      of differentiation, along with a mixture of proliferating and senescent cells,
      under optimal growth-promoting conditions. The responses of human SCs to cAMP
      induced differentiation featured morphological changes and cell cycle exit
      without a concomitant increase in myelin-related proteins and lipids. Human SCs
      efficiently extended processes along those of other SCs (human or rat) but failed
      to do so when placed in co-culture with sensory neurons under conditions
      supportive of myelination. Indeed, axon contact-dependent human SC alignment,
      proliferation, and differentiation were not observed and could not be overcome by
      growth factor supplementation. Strikingly, RNA-seq data revealed that ~ 44 of the
      transcriptome contained differentially expressed genes in human and rat SCs. A
      bioinformatics approach further highlighted that representative SC-specific
      transcripts encoding myelin-related and axon growth-promoting proteins were
      significantly affected and that a deficient expression of key transducers of cAMP
      and adhesion signaling explained the fairly limited potential of human SCs to
      differentiate and respond to axonal cues. These results confirmed the
      significance of combining traditional bioassays and high-resolution genomics
      methods to characterize human SCs and identify genes predictive of cell function
      and therapeutic value.

PMID- 29327209
TI  - Bio-monitoring of Tissue Accumulation and Genotoxic Effect of Heavy Metals in
      Cyprinus carpio from River Kabul Khyber Pakhtunkhwa Pakistan.
AB  - The study explored (I) the concentration of heavy metals in water samples (II)
      their bioaccumulation in common carp Cyprinus carpio (III) and the subsequent
      genotoxicity in the selected organs of carp; from river Kabul, Khyber Pakhtunkhwa
      Pakistan. Except for Mercury (Hg) the water samples had all the heavy metals
      within permissible limits of recommended dietary allowance (RDA). Nonetheless a
      number of heavy metals (Zn, Ni, Cr, Cd, Pb and Hg) showed bioaccumulation at
      levels higher than permissible. Zinc (Zn) was the most while Cadmium (Cd) was the
      least accumulated metal in all tissue samples analyzed. The metal burden in
      different organs of C. carpio was in sequence of intestine > skin > liver > gills
      > muscle. The Comet assay established DNA damage in selected organs to be in
      accordance with metal burden; the most to least damage being in sequence of blood
      > intestine > skin > liver > gills > muscle. In conclusion assessment of DNA
      damage in the organs of C. carpio appears to be a useful bio-marker to evaluate
      genotoxic effects of heavy metal pollution.

PMID- 29327210
TI  - Paired blood cultures increase the sensitivity for detecting pathogens in both
      inpatients and outpatients.
AB  - The objective of this study was to show the differences between paired blood
      cultures (PBC) versus single blood cultures (SBC) in the microbiologic yield, the
      sensitivity to detect pathogens and the time to positivity (TTP). We performed a
      retrospective study examining 112,570 blood culture samples over a 5-year period
      from July 2011 to May 2016 in the BacT/ALERT(r) 3D automated blood culture system
      (bioMerieux, Marcy l'Etoile, France). Bacteria and yeasts were identified using
      the VITEK(r) 2 Compact system (bioMerieux, Marcy l'Etoile, France). True
      positives and contaminated bottles were defined and analysed separately. We
      analysed TTP and adherence to blood volume guidelines for a convenience sample of
      510 and 999 sequential positive cultures, respectively. Out of 49,438 PBC
      samples, 5810 (11.7%) were positive. In 63,132 SBC samples, 4552 (7.2%) were
      positive (p < 0.0001). In PBC, 5371 (10.9%) were true-positives and 439 (0.9%)
      contaminants. In SBC, 4095 (6.5%) were true-positives and 457 (0.7%)
      contaminants. In the inpatient departments (IPD), the most common isolate was
      Escherichia coli (n = 1373), followed by Klebsiella pneumoniae (n = 1206),
      whereas in the outpatient departments (OPD), the most common isolates were
      Salmonella typhi (n = 612) and S. paratyphi A (n = 278). In the analysis of TTP,
      98% grew within 72 h, 91% within 48 h and 89% within 36 h. In the blood volume
      analysis, 90% of the cultures had optimal blood volume. A significantly higher
      positivity rate was seen in PBC compared with SBC. Our study adds to the
      increasing evidence of improved microbial yield of clinically significant
      bacteria and fungi by performing PBC instead of SBC and adhering to blood volume
      collection guidelines.

PMID- 29327206
TI  - Brain Photobiomodulation Therapy: a Narrative Review.
AB  - Brain photobiomodulation (PBM) therapy using red to near-infrared (NIR) light is
      an innovative treatment for a wide range of neurological and psychological
      conditions. Red/NIR light is able to stimulate complex IV of the mitochondrial
      respiratory chain (cytochrome c oxidase) and increase ATP synthesis. Moreover,
      light absorption by ion channels results in release of Ca2+ and leads to
      activation of transcription factors and gene expression. Brain PBM therapy
      enhances the metabolic capacity of neurons and stimulates anti-inflammatory, anti
      apoptotic, and antioxidant responses, as well as neurogenesis and synaptogenesis.
      Its therapeutic role in disorders such as dementia and Parkinson's disease, as
      well as to treat stroke, brain trauma, and depression has gained increasing
      interest. In the transcranial PBM approach, delivering a sufficient dose to
      achieve optimal stimulation is challenging due to exponential attenuation of
      light penetration in tissue. Alternative approaches such as intracranial and
      intranasal light delivery methods have been suggested to overcome this
      limitation. This article reviews the state-of-the-art preclinical and clinical
      evidence regarding the efficacy of brain PBM therapy.

PMID- 29327211
TI  - Twelve Lessons Learned for Effective Research Partnerships Between Patients,
      Caregivers, Clinicians, Academic Researchers, and Other Stakeholders.
AB  - Research increasingly means that patients, caregivers, health professionals,
      other stakeholders, and academic investigators work in partnership. This requires
      effective collaboration rooted in mutual respect, involvement of all
      participants, and good communication. Having conducted such partnered research
      over multiple projects, and having recently completed a project together funded
      by the Patient-Centered Outcomes Research Institute, we collaboratively developed
      a list of 12 lessons we have learned about how to ensure effective research
      partnerships. To foster a culture of mutual respect, hold early in-person
      meetings, with introductions focused on motivation, offer appropriate orientation
      for everyone, and maintain awareness of individual and project goals. To actively
      involve all team members, it is important to ensure sufficient funding for
      everyone's participation, to ask for and recognize diverse contributions, and to
      seek the input of quiet members. To facilitate good communication, teams should
      carefully consider labels, avoid jargon and acronyms, judiciously use homogeneous
      and heterogeneous subgroups, and keep progress visible. In offering pragmatic,
      actionable lessons we have learned through our separate and shared experiences,
      we hope to help foster more patient-centered research via productive and
      enjoyable research collaborations.

PMID- 29327208
TI  - Analysis of DNA modifications in aging research.
AB  - As geroscience research extends into the role of epigenetics in aging and age
      related disease, researchers are being confronted with unfamiliar molecular
      techniques and data analysis methods that can be difficult to integrate into
      their work. In this review, we focus on the analysis of DNA modifications, namely
      cytosine methylation and hydroxymethylation, through next-generation sequencing
      methods. While older techniques for modification analysis performed relative
      quantitation across regions of the genome or examined average genome levels,
      these analyses lack the desired specificity, rigor, and genomic coverage to
      firmly establish the nature of genomic methylation patterns and their response to
      aging. With recent methodological advances, such as whole genome bisulfite
      sequencing (WGBS), bisulfite oligonucleotide capture sequencing (BOCS), and
      bisulfite amplicon sequencing (BSAS), cytosine modifications can now be readily
      analyzed with base-specific, absolute quantitation at both cytosine-guanine
      dinucleotide (CG) and non-CG sites throughout the genome or within specific
      regions of interest by next-generation sequencing. Additional advances, such as
      oxidative bisulfite conversion to differentiate methylation from
      hydroxymethylation and analysis of limited input/single-cells, have great promise
      for continuing to expand epigenomic capabilities. This review provides a
      background on DNA modifications, the current state-of-the-art for sequencing
      methods, bioinformatics tools for converting these large data sets into
      biological insights, and perspectives on future directions for the field.

PMID- 29327212
TI  - A Composite of Functional Status and Pneumonia Severity Index Improves the
      Prediction of Pneumonia Mortality in Older Patients.
AB  - BACKGROUND: The baseline health status may be a determinant of interest in the
      evolution of pneumonia. OBJECTIVE: Our objective was to assess the predictive
      ability of community-acquired pneumonia (CAP) mortality by combining the Barthel
      Index (BI) and Pneumonia Severity Index (PSI) in patients aged >= 65 years.
      DESIGN, PATIENTS AND MAIN MEASURES: In this prospective, observational,
      multicenter analysis of comorbidities, the clinical data, additional examinations
      and severity of CAP were measured by the PSI and functional status by the BI. Two
      multivariable models were generated: Model 1 including the PSI and BI and model 2
      with PSI plus BI stratified categorically. KEY RESULTS: The total population was
      1919 patients, of whom 61% had severe pneumonia (PSI IV-V) and 40.4% had some
      degree of dependence (BI <= 90 points). Mortality in the PSI V-IV group was
      12.5%. Some degree of dependence was associated with increased mortality in both
      the mild (7.2% vs. 3.2%; p = 0.016) and severe (14% vs. 3.3%; p < 0.001)
      pneumonia groups. The combination of PSI IV-V and BI <= 90 was the greatest risk
      factor for mortality (aOR 4.17; 95% CI 2.48 to 7.02) in our series. CONCLUSIONS:
      The use of a bimodal model to assess CAP mortality (PSI + BI) provides more
      accurate prognostic information than the use of each index separately.

PMID- 29327213
TI  - Add-on Treatment with Curcumin Has Antidepressive Effects in Thai Patients with
      Major Depression: Results of a Randomized Double-Blind Placebo-Controlled Study.
AB  - Activation of immune-inflammatory and oxidative-nitrosative (IO&NS) stress
      pathways plays a role in major depression (MDD). Evidence suggests that curcumin
      (500-1000 mg/day), a polyphenol with strong anti-IO&NS properties, may have
      efficacy either as monotherapy or as an adjunctive treatment for depression.
      Further controlled trials with extended treatment periods (> 8 weeks) and higher
      curcumin doses are warranted. This 12-week study was carried out to examine the
      effects of adjunctive curcumin for the treatment of MDD. In this double-blind,
      placebo-controlled trial, 65 participants with MDD were randomized to receive
      either adjunctive curcumin (increasing dose from 500 to 1500 mg/day) or placebo
      for 12 weeks. Four weeks after the active treatment phase, a follow-up visit was
      conducted at week 16. Assessments of the primary, i.e., the Montgomery-Asberg
      Depression Rating Scale (MADRS), and secondary, i.e., the Hamilton Anxiety Rating
      Scale (HAM-A), outcome measures were rated at baseline and 2, 4, 8, 12, and 16
      weeks later. Curcumin was more efficacious than placebo in improving MADRS scores
      with significant differences between curcumin and placebo emerging at weeks 12
      and 16. The effects of curcumin were more pronounced in males compared to
      females. There were no statistically significant treatment-emerging adverse
      effects and no significant effects of curcumin on blood chemistry and ECG
      measurements. Adjunctive curcumin has significant antidepressant effects in
      participants with MDD as evidenced by significant benefits occurring 12 and 16
      weeks after treatment initiation. Curcumin administration was safe and well
      tolerated even when combined with antidepressants. Future trials should include
      treatment-by-sex interactions to examine putative antidepressant effects of
      immune-modifying compounds.

PMID- 29327214
TI  - Interaction effect of job insecurity and role ambiguity on psychological distress
      in Japanese employees: a cross-sectional study.
AB  - PURPOSE: We examined the interaction effect of job insecurity (JI) and role
      ambiguity (RA) on psychological distress in Japanese employees. METHODS: Overall,
      2184 male and 805 female employees from two factories of a manufacturing company
      in Japan completed a self-administered questionnaire comprising the scales
      measuring JI (Job Content Questionnaire), RA (National Institute for Occupational
      Safety and Health Generic Job Stress Questionnaire), psychological distress (K6
      scale), and potential confounders (i.e., age, education, family size,
      occupational class, and work shift). Taking psychological distress as a dependent
      variable, hierarchical multiple regression analyses were conducted by gender and
      employment status (i.e., permanent and non-permanent employees). An interaction
      term of JI * RA was included in the model. RESULTS: After adjusting for potential
      confounders, the main effects of JI and RA on psychological distress were
      significant regardless of gender or employment status. Furthermore, the
      significant interaction effect of JI * RA on psychological distress was observed
      among permanent male employees (beta = 0.053, p = 0.010). Post hoc simple slope
      analyses showed that the simple slope of JI was greater at higher levels of RA
      (i.e., one standard deviation [SD] above the mean) (beta = 0.300, p < 0.001)
      compared to lower levels of RA (i.e., one SD below the mean) (beta = 0.212, p <
      0.001). On the other hand, the interaction effect of JI * RA was not significant
      among permanent or non-permanent female employees. CONCLUSIONS: The present study
      suggests that higher levels of RA strengthen the association of JI with
      psychological distress, at least among Japanese permanent male employees.

PMID- 29327215
TI  - Treatment outcomes of using inhalation sedation for comprehensive dental care.
AB  - AIM: To assess the outcomes of dental treatment under inhalation sedation within
      a UK specialist hospital setting. METHODS: This was a retrospective cohort study
      of the case notes of patients under 17 years of age who received dental treatment
      using inhalation sedation at a UK specialist setting during the period 2006-2011.
      Treatment outcomes were categorised into five groups: (1) treatment completed as
      planned, (2) modified treatment completed, (3) treatment abandoned in sedation
      unit and patient referred for treatment under general analgesia (GA), (4)
      treatment abandoned in sedation unit and patient referred for treatment under
      local analgesia (LA), (5) child failed to return to complete treatment. RESULTS:
      In total, the case notes of 453 patients were evaluated. The mean age of the
      patients was 10.3 +/- 2.9 years. Treatment was completed successfully in 63.6% of
      the cases, 15.9% were referred for treatment under GA, 11.2% failed to return to
      complete the treatment, 7.1% received modified treatment completed, and only 2.2%
      were referred for treatment under LA. Treatment outcomes were significantly
      associated with patient's age (p = 0.002). The treatment outcome "treatment
      abandoned and child referred to be treated under GA" had significantly lower mean
      patient ages than the other outcomes. CONCLUSIONS: The majority of children
      referred for inhalation sedation, completed their course of treatment. A
      significantly higher proportion of those in the younger age group required GA to
      complete their treatment.

PMID- 29327216
TI  - Dental erosion, prevalence and risk factors among a group of adolescents in
      Stockholm County.
AB  - AIMS: To investigate the prevalence and risk factors of dental erosion (DE) among
      a group of adolescents in Stockholm County. MATERIALS AND METHODS: This cross
      sectional cohort study was conducted at three clinics of the Public Dental
      Service in Stockholm County. Fifteen and 17 year old adolescents (1335) who
      scheduled their regular dental health examination were asked to participate.
      After drop-outs a sample of 1071 individuals, 547 males and 524 females were
      enrolled in the study. Presence of erosive wear was diagnosed (yes/no) on marker
      teeth by trained dentists/dental hygienists and photographs were taken. The
      adolescents answered a questionnaire regarding oral symptoms, dietary and
      behavioural factors. Two calibrated specialist dentists performed evaluation of
      the photographs for severity of DE using a modified version of the Simplified
      Erosion Partial Recording System (SEPRS). RESULTS: DE was clinically diagnosed in
      28.3% of 15 years old and 34.3% of 17 years old. Severe erosive wear (grade 3 and
      4 according to SEPRS) was found in 18.3% of the adolescents based upon the intra
      oral photographs. DE was more prevalent and severe among males than females.
      Clinically diagnosed erosive lesions correlated significantly with soft drink
      consumption (p < 0.001), the use of juice or sport drinks as a thirst quencher
      after exercise (p = 0.006) and tooth hypersensitivity when eating and drinking (p
      = 0.012). Furthermore, self-assessed gastric reflux was a factor strongly
      associated with DE (p < 0.001). CONCLUSION: The study indicated that DE was
      common among adolescents in Stockholm County and associated with both internal
      and external risk factors.

PMID- 29327217
TI  - Cryobiotechnology of apple (Malus spp.): development, progress and future
      prospects.
AB  - KEY MESSAGE: Cryopreservation provides valuable genes for further breeding of
      elite cultivars, and cryotherapy improves the production of virus-free plants in
      Malus spp., thus assisting the sustainable development of the apple industry.
      Apple (Malus spp.) is one of the most economically important temperate fruit
      crops. Wild Malus genetic resources and existing cultivars provide valuable genes
      for breeding new elite cultivars and rootstocks through traditional and
      biotechnological breeding programs. These valuable genes include those resistant
      to abiotic factors such as drought and salinity, and to biotic factors such as
      fungi, bacteria and aphids. Over the last three decades, great progress has been
      made in apple cryobiology, making Malus one of the most extensively studied plant
      genera with respect to cryopreservation. Explants such as pollen, seeds, in vivo
      dormant buds, and in vitro shoot tips have all been successfully cryopreserved,
      and large Malus cryobanks have been established. Cryotherapy has been used for
      virus eradication, to obtain virus-free apple plants. Cryopreservation provided
      valuable genes for further breeding of elite cultivars, and cryotherapy improved
      the production of virus-free plants in Malus spp., thus assisting the sustainable
      development of the apple industry. This review provides updated and comprehensive
      information on the development and progress of apple cryopreservation and
      cryotherapy. Future research will reveal new applications and uses for apple
      cryopreservation and cryotherapy.

PMID- 29327218
TI  - Online Communication about Depression and Anxiety among Twitter Users with
      Schizophrenia: Preliminary Findings to Inform a Digital Phenotype Using Social
      Media.
AB  - Digital technologies hold promise for supporting the detection and management of
      schizophrenia. This exploratory study aimed to generate an initial understanding
      of whether patterns of communication about depression and anxiety on popular
      social media among individuals with schizophrenia are consistent with offline
      representations of the illness. From January to July 2016, posts on Twitter were
      collected from a sample of Twitter users who self-identify as having a
      schizophrenia spectrum disorder (n = 203) and a randomly selected sample of
      control users (n = 173). Frequency and timing of communication about depression
      and anxiety were compared between groups. In total, the groups posted n =
      1,544,122 tweets and users had similar characteristics. Twitter users with
      schizophrenia showed significantly greater odds of tweeting about depression
      compared with control users (OR = 2.69; 95% CI 1.76-4.10), and significantly
      greater odds of tweeting about anxiety compared with control users (OR = 1.81;
      95% CI 1.20-2.73). This study offers preliminary insights that Twitter users with
      schizophrenia may express elevated symptoms of depression and anxiety in their
      online posts, which is consistent with clinical characteristics of schizophrenia
      observed in offline settings. Social media platforms could further our
      understanding of schizophrenia by informing a digital phenotype and may afford
      new opportunities to support early illness detection.

PMID- 29327220
TI  - Patient Perceptions and Preferences for a Mealtime Insulin Delivery Patch.
AB  - INTRODUCTION: A basal-bolus insulin regimen is needed to achieve glycated
      hemoglobin A1c (HbA1c) below 7.0% in people with type 1 (T1D) or type 2 (T2D)
      diabetes who have significant loss of beta-cell function. Nonadherence to therapy
      is common and negatively affects the ability to reach treatment goals. We
      examined patient assessment of a new, wearable mealtime insulin-delivery system
      (patch) relative to their current mealtime insulin-delivery system (syringe, pen,
      or pump). The patch is designed to deliver only boluses of fast-acting insulin
      (no basal insulin), mechanically controlled by the patient. METHODS: Adults (n =
      101) with T1D or T2D assessed their current mealtime insulin-delivery system and
      then assessed simulated (no active medication) patch use over a 3-day period.
      Participants evaluated mealtime insulin-delivery systems using eight measures
      from five domains (convenience, interference with daily activities, diabetes
      related worry, psychological well-being, and overall satisfaction/preference) on
      the self-administered Insulin Delivery System Rating Questionnaire. User ratings
      of their current insulin-delivery systems (syringe, pen, pump) were compared with
      those for the patch by repeated measure analysis of variance and one-sample t
      tests. RESULTS: Participants had significant (p < 0.05) preference for patch over
      syringe in all eight comparisons, and over pen in five out of eight comparisons,
      with no significant preference for pen. Although there was a preference for patch
      over pump in six out of eight comparisons, only one showed a significant
      preference for patch, and one for pump. Significantly more participants reported
      that they would like to switch to the patch than continue using a syringe (78% vs
      22%) or pen (76% vs 24%) but this difference was not significant for the group
      using a pump (52% vs 48%). CONCLUSIONS: Participants preferred using the patch
      over pens and syringes. Its ease of use and discreet method of insulin delivery
      may contribute to improved patient adherence to mealtime insulin regimens among
      people currently using injection devices. FUNDING: Calibra Medical.

PMID- 29327221
TI  - Whole cell solid-state NMR study of Chlamydomonas reinhardtii microalgae.
AB  - In vivo or whole-cell solid-state NMR is an emerging field which faces tremendous
      challenges. In most cases, cell biochemistry does not allow the labelling of
      specific molecules and an in vivo study is thus hindered by the inherent
      difficulty of identifying, among a formidable number of resonances, those arising
      from a given molecule. In this work we examined the possibility of studying, by
      solid-state NMR, the model organism Chlamydomonas reinhardtii fully and non
      specifically 13C labelled. The extension of NMR-based dynamic filtering from one
      dimensional to two-dimensional experiments enabled an enhanced selectivity which
      facilitated the assignment of cell constituents. The number of resonances
      detected with these robust and broadly applicable experiments appears to be
      surprisingly sparse. Various constituents, notably galactolipids abundant in
      organelle membranes, carbohydrates from the cell wall, and starch from storage
      grains could be unambiguously assigned. Moreover, the dominant crystal form of
      starch could be determined in situ. This work illustrates the feasibility and
      caveats of using solid-state NMR to study intact non-specifically 13C labelled
      micro-organisms.

PMID- 29327223
TI  - One-bone forearm osteodesis and biceps re-routing to correct severe supination
      contracture in a paediatric patient with late obstetric brachial plexus palsy.
AB  - PURPOSE: The one-bone forearm arthrodesis has been performed to change the
      position of the forearm in children with fixed supination deformity due to upper
      extremity neurologic deficit. In this article, we present a retrospective review
      of children with late obstetric brachial plexus palsy who underwent palliative
      surgery to correct severe supination contracture by one-bone forearm osteodesis
      and biceps re-routing. This technique has not been described previously.
      MATERIALS AND METHODS: In this retrospective study, four consecutive patients
      with upper extremity weakness and severe supination contracture who underwent
      forearm osteodesis in neutral or slight pronation and biceps re-routing. The
      average age of patients at the time of surgery was 12 years six months (range, 7
      14 years). RESULTS: The average follow-up was one year ten months (range, 1 year
      6 months to 2 years 7 months). The rotation of the forearm set in neutral (3
      patients) and 15 degrees  pronation (1 patient). No patients noted adverse
      effects on the shoulder, elbow or wrist, and none missed having forearm rotation.
      CONCLUSIONS: One-bone forearm osteodesis and biceps re-routing technique should
      be considered in some patients with fixed forearm supination deformity and
      concomitant severe pronation deficit. In this group of patients, repositioning
      the forearm in a more pronated (or less supinated) position may improve the use
      of that extremity in activities of daily living. The surgical technique is fairly
      simple and can be done in a single procedure.

PMID- 29327222
TI  - (3, 2)D 1H, 13C BIRDr,X-HSQC-TOCSY for NMR structure elucidation of mixtures:
      application to complex carbohydrates.
AB  - Overlap of NMR signals is the major cause of difficulties associated with NMR
      structure elucidation of molecules contained in complex mixtures. A 2D
      homonuclear correlation spectroscopy in particular suffers from low dispersion of
      1H chemical shifts; larger dispersion of 13C chemical shifts is often used to
      reduce this overlap, while still providing the proton-proton correlation
      information e.g. in the form of a 2D 1H, 13C HSQC-TOCSY experiment. For this
      methodology to work, 13C chemical shift must be resolved. In case of 13C chemical
      shifts overlap, 1H chemical shifts can be used to achieve the desired resolution.
      The proposed (3, 2)D 1H, 13C BIRDr,X-HSQC-TOCSY experiment achieves this while
      preserving singlet character of cross peaks in the F1 dimension. The required
      high-resolution in the 13C dimension is thus retained, while the cross peak
      overlap occurring in a regular HSQC-TOCSY experiment is eliminated. The method is
      illustrated on the analysis of a complex carbohydrate mixture obtained by
      depolymerisation of a fucosylated chondroitin sulfate isolated from the body wall
      of the sea cucumber Holothuria forskali.

PMID- 29327224
TI  - Prevalence and clinical characteristics of headache in juvenile myoclonic
      epilepsy: experience from a tertiary epilepsy center.
AB  - The comorbidity of headache and epilepsy is often seen in neurological practice.
      The objective of this study was to assess the prevalence, types of, and risk
      factors for headache in juvenile myoclonic epilepsy (JME). We assessed a total of
      200 patients and 100 healthy controls in our study. Headache was classified in
      participants using a self-administered questionnaire. Demographical, clinical
      features and headache characteristics were recorded. Seizure and headache
      temporal profiles were noted. Headache was present in 111 (56%) patients and 50
      (50%) healthy participants. From these patients, 47 (42.3%) JME patients had
      migraine [30 (27%) migraine without aura (MO), 17 (15.3%) migraine with aura
      (MA)], 52 (46.8%) had tension type headache (TTH), 4 (3.6%) had both migraine and
      TTH, and 8 (7.2%) had other non-primary headaches. In the healthy control group,
      migraine was detected in 16 (32%) subjects, TTH in 33 (66%), both migraine and
      TTH in 1 (2%) subject. A positive migraine family history and symptom relief with
      sleep were more frequent in JME patients (p = 0.01). Headache was classified as
      inter-ictal in 82 (79.6%) patients and peri-ictal in 21 (20.4%) patients. In
      conclusion, the present study revealed that headache frequency was not
      significantly different between JME patients and healthy controls (p > 0.05).
      However, migraine frequency was higher in JME patients than healthy controls.
      Some migraine and TTH characteristics were different in between groups. We
      suggest that our results support both genetic relationship and shared underlying
      hypothetical pathopysiological mechanisms between JME and headache, especially
      migraine.

PMID- 29327219
TI  - Pharmacological Insights into the Use of Apomorphine in Parkinson's Disease:
      Clinical Relevance.
AB  - The present paper consists of a comprehensive review of the literature on
      apomorphine pharmacological properties and its usefulness in Parkinson's disease
      (PD). The chemistry, structure-activity relationship, pharmacokinetics and
      pharmacodynamics of apomorphine are described with regard to its effects on PD
      symptoms, drug interactions, interindividual variability and adverse events.
      Apomorphine chemical structure accounts for most of its beneficial and
      deleterious properties, both dopaminergic and non-dopaminergic. Its
      pharmacokinetics and pharmacodynamics are complex and subject to interindividual
      variability, particularly for subcutaneous absorption and metabolism.
      Subcutaneous apomorphine, either as injections or infusion, is particularly
      useful for the treatment of PD motor symptoms and growing evidence supports its
      clinical value for nonmotor disorders. Owing to interindividual variability and
      sensitivity, apomorphine treatment must be tailored to each patient. While the
      subcutaneous route has been the gold standard for decades, the search for
      alternative routes is ongoing, with promising results from studies of pulmonary,
      sublingual and transdermal routes. In addition, the potential of apomorphine as a
      disease-modifying therapy deserves to be investigated, as well as its ability to
      induce brain plasticity through chronic infusion. Moreover, the ongoing progress
      in the development of analytical methods should be accompanied by new
      pharmacokinetic and pharmacodynamic studies of apomorphine metabolism and sites
      of action in humans, as its biochemistry has yet to be fully described.

PMID- 29327226
TI  - Type D Personality and Sleep Quality in Coronary Artery Disease Patients With and
      Without Obstructive Sleep Apnea: Mediating Effects of Anxiety and Depression.
AB  - PURPOSE: The study aimed to examine the association between type D personality
      trait and sleep quality in coronary artery disease (CAD) patients with and
      without obstructive sleep apnea (OSA) and to explore the mediating effects of
      anxiety and depression symptoms. METHOD: A cross-sectional study was performed in
      879 CAD patients attending cardiac rehabilitation program (mean age 57.8 years;
      SD = 9.0; 75% men). Participants underwent full-night polysomnography and were
      classified in OSA (n = 349) and no OSA (n = 530) groups. Patients were evaluated
      for type D personality, subjective sleep quality (Pittsburgh sleep quality
      index), and symptoms of anxiety and depression (hospital anxiety and depression
      scale). RESULTS: Patients with type D personality reported poorer subjective
      sleep quality than non-type D patients irrespective of the presence of OSA. Type
      D and negative affectivity (NA) were associated with worse subjective sleep
      quality in patients with OSA and without OSA. The mediational analysis revealed
      that type D and NA were indirectly associated with Pittsburgh sleep quality index
      through anxiety and depression symptoms in no OSA and OSA patients. CONCLUSION:
      In CAD patients, type D personality and NA are associated with worse subjective
      sleep quality and this association is mediated by depression and anxiety symptoms
      irrespective of OSA presence.

PMID- 29327225
TI  - News on the journal Neurological Sciences in 2017.

PMID- 29327228
TI  - Postoperative intermittent fasting prevents hippocampal oxidative stress and
      memory deficits in a rat model of chronic cerebral hypoperfusion.
AB  - PURPOSE: Whether intermittent fasting (IF) treatment after stroke can prevent its
      long-term detrimental effects remains unknown. Here, we investigate the effects
      of postoperative IF on cognitive deficits and its underlying mechanisms in a
      permanent two-vessel occlusion (2VO) vascular dementia rat model. METHODS: Rats
      were subjected to either IF or ad libitum feeding 1 week after 2VO surgery. The
      cognition of rats was assessed using the novel object recognition (NOR) task and
      Morris water maze (MWM) 8 weeks after surgery. After behavioral testing,
      hippocampal malondialdehyde (MDA) and glutathione (GSH) concentrations,
      superoxide dismutase (SOD) activity, gene expression of antioxidative enzymes,
      inflammatory protein levels, and microglia density were determined. RESULTS:
      Postoperative IF significantly ameliorated the cognitive performance of 2VO rats
      in the NOR and MWM tests. Cognitive enhancement paralleled preservation of the
      PSD95 and BDNF levels in the 2VO rat hippocampus. Mechanistically, postoperative
      IF mitigated hippocampal oxidative stress in 2VO rats, as indicated by the
      reduced MDA concentration and mRNA and the protein levels of the reactive oxygen
      species-generating enzyme nicotinamide adenine dinucleotide phosphate oxidase 1.
      IF treatment also preserved the GSH level and SOD activity, as well as the levels
      of their upstream regulating enzymes, resulting in preserved antioxidative
      capability. In addition, postoperative IF prevented hippocampal microglial
      activation and elevation of sphingosine 1-phosphate receptor 1 and inflammatory
      cytokines in 2VO rats. CONCLUSIONS: Our results suggest that postoperative IF
      suppresses neuroinflammation and oxidative stress induced by chronic cerebral
      ischemia, thereby preserving cognitive function in a vascular dementia rat model.

PMID- 29327229
TI  - Leopoldia comosa prevents metabolic disorders in rats with high-fat diet-induced
      obesity.
AB  - PURPOSE: Obesity is the main feature of a complex illness known as metabolic
      syndrome. Anti-obesogenic therapies are often associated with side effects and
      represent a high cost in conventional pharmacological approaches. New strategies
      based on natural remedies are under continuous investigation. Leopoldia comosa
      (L.) Parl. (L. comosa) is a spontaneous plant with diuretic, anti-inflammatory
      and antioxidant properties. Recently, a hypoglycemic activity mediated by
      inhibition of carbohydrate digestion has been identified. The aim of this study
      was to evaluate the effects of a diet supplemented with L. comosa extracts on a
      rat model of diet-induced obesity. METHODS: Leopoldia comosa bulb extracts were
      obtained using a dynamic extractor. Phytochemical properties and in vitro
      determination of the antioxidant activity and of the inhibitory effects on lipase
      and pancreatic amylase were performed. Rats were fed (12 weeks) a standard diet,
      or a high-fat diet (HFD), or an HFD plus L. comosa (20 or 60 mg/die) extracts.
      The metabolic and anthropometric parameters were recorded. RESULTS: Results
      indicated that L. comosa inhibited lipase and pancreatic amylase activities. In
      vivo data showed that the supplementation with both doses of L. comosa extracts
      counteracted the HFD-dependent effects. It reduced body weight, abdominal obesity
      and dyslipidemia, and improved glucose tolerance with a reduction of lipidic
      tissue hypertrophy and liver steatosis, as compared to HFD-fed rat. In liver, L.
      comosa reduced protein expression levels of PEPCK and G6Pase. CONCLUSION: We
      suggest that L. comosa extracts prevent obesity-dependent metabolic disorders.
      This paves the way for their therapeutic application as a natural anti-obesity
      drug.

PMID- 29327227
TI  - Structural characterization of a novel full-length transcript promoter from
      Horseradish Latent Virus (HRLV) and its transcriptional regulation by multiple
      stress responsive transcription factors.
AB  - KEY MESSAGE: The promoter fragment described in this study can be employed for
      strong transgene expression under both biotic and abiotic stress conditions.
      Plant-infecting Caulimoviruses have evolved multiple regulatory mechanisms to
      address various environmental stimuli during the course of evolution. One such
      mechanism involves the retention of discrete stress responsive cis-elements which
      are required for their survival and host-specificity. Here we describe the
      characterization of a novel Caulimoviral promoter isolated from Horseradish
      Latent Virus (HRLV) and its regulation by multiple stress responsive
      Transcription factors (TFs) namely DREB1, AREB1 and TGA1a. The activity of full
      length transcript (Flt-) promoter from HRLV (- 677 to + 283) was investigated in
      both transient and transgenic assays where we identified H12 (- 427 to + 73) as
      the highest expressing fragment having ~ 2.5-fold stronger activity than the
      CaMV35S promoter. The H12 promoter was highly active and near-constitutive in the
      vegetative and reproductive parts of both Tobacco and Arabidopsis transgenic
      plants. Interestingly, H12 contains a distinct cluster of cis-elements like
      dehydration-responsive element (DRE-core; GCCGAC), an ABA-responsive element
      (ABRE; ACGTGTC) and as-1 element (TGACG) which are known to be induced by cold,
      drought and pathogen/SA respectively. The specific binding of DREB1, AREB1 and
      TGA1a to DRE, ABRE and as-1 elements respectively were confirmed by the gel
      binding assays using H12 promoter-specific probes. Detailed mutational analysis
      of the H12 promoter suggested that the presence of DRE-core and as-1 element was
      indispensable for its activity which was further confirmed by the transactivation
      assays. Our studies imply that H12 could be a valuable genetic tool for regulated
      transgene expression under diverse environmental conditions.

PMID- 29327231
TI  - Loading of the Condylar Cartilage Can Rescue the Effects of Botox on TMJ.
AB  - The purpose of this study is to evaluate whether the effects of botulinum
      neurotoxin (botox) injection into the masseter in the mandibular condylar
      cartilage (MCC) and subchondral bone could be rescued by compressive loading of
      the temporomandibular joint (TMJ). Twenty-four 6-week-old female mice (C57BL/6J)
      were used. Mice were divided in three groups: (1) Botox (n = 8); (2) Botox plus
      loading (n = 8); (3) Pure control (n = 8). Bone labels (3 and 1 day before
      sacrifice) and the proliferation marker EdU (2 and 1 day before sacrifice) were
      intraperitoneally injected into all groups of mice. Condyles were dissected and
      examined by micro-CT and histology. Sagittal sections of condyles were stained
      for TRAP, alkaline phosphatase, EdU, TUNEL, and toluidine blue. In addition,
      immunostaining for pSmad, VEGF, and Runx2 was performed. Bone volume fraction,
      tissue density, and trabecular thickness were significantly decreased on the
      subchondral bone of botox-injected side when compared to control side and control
      mice, 4 weeks after injection. Furthermore, histological analysis revealed
      decrease in mineralization, matrix deposition, TRAP activity, EdU, and TUNEL
      positive cells in the MCC of the botox-injected side, 4 weeks after injection.
      However, compressive loading reversed the reduced bone volume and density and the
      cellular changes in the MCC caused by Botox injection. TMJ compressive loading
      rescues the negative effects of botox injection into the masseter in the MCC and
      subchondral bone.

PMID- 29327230
TI  - Alcohol, alcoholic beverages, and melanoma risk: a systematic literature review
      and dose-response meta-analysis.
AB  - PURPOSE: Several studies in recent years have investigated the relationship
      between alcohol intake and melanoma risk, with conflicting results. To help
      clarify this issue, we conducted a literature review and dose-response meta
      analysis of studies published until June 30th, 2017, that examined the
      association between alcohol intake (overall and by beverage type) and melanoma
      risk. METHODS: We used random effect models with maximum likelihood estimation to
      calculate summary relative risk (SRR) and 95% confidence intervals (95%CI).
      RESULTS: We included 20 independent studies (encompassing 10,555 melanoma cases
      and over 1.6 million non-cases/controls) published during 1986-2016, of which six
      had a prospective cohort study design. Adjustment for phenotypic characteristics
      and sunlight exposure was performed in 11 and nine studies, respectively. Alcohol
      intake was moderately associated with melanoma risk: the SRR were 1.29 (95% CI
      1.14-1.45) for those in the highest vs. lowest category of current alcohol
      intake, and 1.96 (95% CI 1.02-3.76, I2 = 0%) for cumulative intake. In the dose
      response analysis, the increase in risk associated with a 10 g increment in daily
      alcohol intake was 1.07 (95% CI 1.03-1.11). Risk estimates did not differ by
      gender, study design and adjustment for confounders; between-studies
      heterogeneity was acceptable, and there was no evidence of publication bias.
      CONCLUSIONS: Our findings suggest that alcohol drinking may be moderately
      associated with increased melanoma risk, although residual confounding and bias
      cannot be ruled out. Further research is needed to confirm these findings,
      clarify the role of the different alcohol sources, and investigate the
      interaction with known melanoma risk factors.

PMID- 29327232
TI  - Comparative evaluation of the Omniplex-HPV and RFMP HPV PapilloTyper for
      detecting human papillomavirus genotypes in cervical specimens.
AB  - Human papillomavirus (HPV) is a major cause of cervical neoplasia development.
      HPV screening is very important because early treatment can prevent cervical
      cancer. Omniplex-HPV is a polymerase chain reaction followed by Luminex xMAP bead
      microarray technology that is designed for detecting 40 HPV genotypes. The aim of
      this study is to evaluate the analytical and clinical performance of the Omniplex
      HPV in comparison with that of the commercially available RFMP (restriction
      fragment mass polymorphism) HPV PapilloTyper. A total of 2,808 cervical swab
      specimens were obtained. Of these, only 1799 specimens had a cytology result. A
      type-specific direct sequencing test was performed using the reference method in
      case of discrepancies between the two test results. The overall percent agreement
      (OPA) between Omniplex-HPV and RFMP HPV PapilloTyper was 97.9% (kappa=0.84; 95%
      CI: 0.81-0.88). The positive percent agreement (PPA) and the negative percent
      agreement (NPA) were 98.0% and 96.2%, respectively. The Omniplex-HPV and RFMP HPV
      PapilloTyper showed comparable sensitivities (90.2% and 91.9%, respectively) and
      specificities (91.3% each), while the Omniplex-HPV produced more accurate results
      and required less turnaround time and labor. The agreement between these two
      methods was excellent for HPV genotyping (P>0.05; McNemar's test), and clinical
      sensitivity, specificity, and odds ratio of the two assays were comparable to the
      result of cytology tests in identifying high risk HPV. In conclusion, Omniplex
      HPV and RFMP HPV PapilloTyper were highly comparable with regard to detection and
      genotyping analysis of HPV.

PMID- 29327233
TI  - DCAF1 is involved in HCV replication through regulation of miR-122.
AB  - Hepatitis C virus (HCV) is a worldwide threaten to human health with a high ratio
      of chronic infections. Recently, we found that Vpr-mediated regulation of HCV
      replication depends on the host protein DDB1-Cul4 associate factor 1 (DCAF1),
      implying that DCAF1 might be involved in the replication of HCV. In this study,
      we demonstrated that DCAF1 knockdown reduced HCV replication both in the
      infectious (JFH1) and replicon (Con1) systems. Further investigation showed a
      negative regulation of HCV internal ribosome entry site (IRES)-mediated
      translation by DCAF1. Considering the positive effects on the replication of the
      HCV replicon, we speculated that DCAF1 affected the balance between HCV RNA
      replication and protein translation. Since miR-122 is involved in the regulation
      of this balance, we investigated the influence of DCAF1 on miR-122 expression. By
      measuring the expression of miR-122, pre-miR-122 and its target CAT-1 mRNA, we
      found that miR-122 was downregulated following DCAF1 knockdown. Furthermore,
      overexpression of miR-122 rescued HCV replication impairment induced by DCAF1
      knockdown. In conclusion, our study suggests that DCAF1 is involved in HCV
      replication through regulation of miR-122 and thus provides new insights into the
      interaction between HCV and the host cell.

PMID- 29327234
TI  - Antiviral effect of lithium chloride on replication of avian leukosis virus
      subgroup J in cell culture.
AB  - Lithium chloride (LiCl) has been reported to possess antiviral activity against
      several viruses. In the current study, we assessed the antiviral activity effect
      of LiCl on ALV-J infection in CEF cells by using real-time PCR, Western blot
      analysis, IFA and p27 ELISA analysis. Our results showed that both viral RNA copy
      number and protein level decreased significantly in a dose and time dependent
      manner. Time-course analysis revealed that the antiviral effect was more
      pronounced when CEFs were treated at the post infection stage rather than at
      early absorption or pre-absorption stages. Further experiments demonstrated that
      LiCl did not affect virus attachment or entry, but rather affected early virus
      replication. We also found that inhibition of viral replication after LiCl
      treatment was associated with reduced mRNA levels of pro-inflammatory cytokines.
      These results demonstrate that LiCl effectively blocked ALV-J replication in CEF
      cells and may be used as an antiviral agent against ALV-J.

PMID- 29327235
TI  - Complete genome sequence of a phage hyperparasite of Candidatus Xenohaliotis
      californiensis (Rickettsiales) - a pathogen of Haliotis spp (Gasteropoda).
AB  - Bacteriophages are recognized as major mortality agents of microbes, among them
      intracellular marine rickettsiales-like bacteria. Recently, a phage hyperparasite
      of Candidatus Xenohaliotis californiensis (CXc) has been described. This
      bacterium is considered the causal agent of Withering Syndrome (WS) which is a
      chronic and potentially lethal disease of abalone species from California, USA
      and the peninsula of Baja California, Mexico. This hyperparasite which infects
      CXc could be used as a biocontrol agent for WS. Therefore, it is necessary to
      obtain genomic information to characterize this phage. In this study, the first
      complete genome sequence of a novel phage, Xenohaliotis phage (pCXc) was
      determined. The complete genome of pCXc from red abalone (Haliotis rufescens) is
      35,728 bp, while the complete genome of pCXc from yellow abalone (Haliotis
      corrugata) is 35,736 bp. Both phage genomes consist of double-stranded DNA with a
      G + C content of 38.9%. In both genomes 33 open reading frames (ORFs) were
      predicted. Only 10 ORFs encode proteins that have identifiable functional
      homologues. These 10 ORFs were classified by function, including structural, DNA
      replication, DNA packaging, nucleotide transport and metabolism, life cycle
      regulation, recombination and repair, and additional functions. A PCR method for
      the specific detection of pCXc was developed. This information will help to
      understand a new group of phages that infect intracellular marine rickettsiales
      like bacteria in mollusks.

PMID- 29327236
TI  - Complete genome sequence and construction of an infectious full-length cDNA clone
      of a German isolate of celery mosaic virus.
AB  - The complete genome sequence of a German isolate of celery mosaic virus (CeMV, a
      potyvirus) from Quedlinburg (DSMZ PV-1003) was determined (MF962880). This
      represents the second fully sequenced genome of this virus, along with a
      Californian isolate (HQ676607.1). The positive-sense single-stranded RNA is
      10,000 nucleotides in length and shows the typical organization of potyviruses
      but has a shorter PIPO than CeMV California. In comparison to CeMV isolates from
      different origins, CeMV-Quedlinburg and isolates from the Netherlands
      (AF203531.1) and Aschersleben, Germany (AJ271087.1) show a NAG instead of DAG in
      the region of the coat protein responsible for aphid transmission. In this study
      the first infectious full-length clone of celery mosaic virus was obtained and
      the infectivity confirmed by Rhizobium radiobacter infiltration of Apium species.

PMID- 29327237
TI  - Regional, age and respiratory-secretion-specific prevalence of respiratory
      viruses associated with asthma exacerbation: a literature review.
AB  - Despite increased understanding of how viral infection is involved in asthma
      exacerbations, it is less clear which viruses are involved and to what extent
      they contribute to asthma exacerbations. Here, we sought to determine the
      prevalence of different respiratory viruses during asthma exacerbations.
      Systematic computerized searches of the literature up to June 2017 without
      language limitation were performed. The primary focus was on the prevalence of
      respiratory viruses, including AdV (adenovirus), BoV (bocavirus), CoV
      (coronavirus), CMV (cytomegalovirus), EnV (enterovirus), HSV (herpes simplex
      virus), IfV (influenza virus), MpV (metapneumovirus), PiV (parainfluenzavirus),
      RV (rhinovirus) and RSV (respiratory syncytial virus) during asthma
      exacerbations. We also examined the prevalence of viral infection stratified by
      age, geographic region, type of respiratory secretion, and detection method.
      Sixty articles were included in the final analysis. During asthma exacerbations,
      the mean prevalence of AdV, BoV, CoV, CMV, EnV, HSV, IfV, MpV, PiV, RV and RSV
      was 3.8%, 6.9%, 8.4%, 7.2%, 10.1%, 12.3%, 10.0%, 5.3%, 5.6%, 42.1% and 13.6%,
      respectively. EnV, MPV, RV and RSV were more prevalent in children, whereas AdV,
      BoV, CoV, IfV and PiV were more frequently present in adults. RV was the major
      virus detected globally, except in Africa. RV could be detected in both the upper
      and lower airway. Polymerase chain reaction was the most sensitive method for
      detecting viral infection. Our findings indicate the need to develop prophylactic
      polyvalent or polyvirus (including RV, EnV, IfV and RSV) vaccines that produce
      herd immunity and reduce the healthcare burden associated with virus-induced
      asthma exacerbations.

PMID- 29327238
TI  - The complete genome sequence of HetPV20-an1, an alphapartitivirus infecting the
      conifer-pathogenic fungus Heterobasidion annosum.
AB  - Root rot fungi of the genus Heterobasidion are highly destructive conifer
      pathogens in the northern Boreal forest region. This report describes the
      complete genome sequence of Heterobasidion partitivirus 20 infecting a Finnish
      strain of Heterobasidion annosum. The bisegmented dsRNA genome of HetPV20-an1
      encodes a predicted RNA-dependent RNA polymerase of 605 amino acids (aa) and a
      capsid protein of 536 aa. Based on sequence similarity and phylogenetic analysis,
      this virus is a new member of the genus Alphapartitivirus. HetPV20-an1 shares
      ~65% RdRP aa sequence identity with the most similar virus strain, Rosellinia
      necatrix partitivirus 2, whereas the CP of HetPV20-an1 is most similar to that of
      rose partitivirus with ~27% overall aa sequence identity. HetPV20-an1 is only
      distantly related to previously known partitiviruses of Heterobasidion species
      and shares ~29% RdRP aa sequence identity and ~16% CP aa sequence identity with
      Heterobasidion partitivirus 1 from H. abietinum.

PMID- 29327239
TI  - A small protein probe for correlated microscopy of endogenous proteins.
AB  - Probes are essential to visualize proteins in their cellular environment, both
      using light microscopy as well as electron microscopy (EM). Correlated light
      microscopy and electron microscopy (CLEM) requires probes that can be imaged
      simultaneously by both optical and electron-dense signals. Existing combinatorial
      probes often have impaired efficiency, need ectopic expression as a fusion
      protein, or do not target endogenous proteins. Here, we present FLIPPER-bodies to
      label endogenous proteins for CLEM. Fluorescent Indicator and Peroxidase for
      Precipitation with EM Resolution (FLIPPER), the combination of a fluorescent
      protein and a peroxidase, is fused to a nanobody against a target of interest.
      The modular nature of these probes allows an easy exchange of components to
      change its target or color. A general FLIPPER-body targeting GFP highlights
      histone2B-GFP both in fluorescence and in EM. Similarly, endogenous EGF receptors
      and HER2 are visualized at nm-scale resolution in ultrastructural context. The
      small and flexible FLIPPER-body outperforms IgG-based immuno-labeling, likely by
      better reaching the epitopes. Given the modular domains and possibilities of
      nanobody generation for other targets, FLIPPER-bodies have high potential to
      become a universal tool to identify proteins in immuno-CLEM with increased
      sensitivity compared to current approaches.

PMID- 29327240
TI  - Geriatric oncology in Spain: survey results and analysis of the current
      situation.
AB  - INTRODUCTION: Geriatric oncology (GO) is a discipline that focuses on the
      management of elderly patients with cancer. The Spanish Society of Medical
      Oncology (SEOM) created a Working group dedicated to geriatric oncology in
      February 2016. OBJECTIVES: The main goal of this study was to describe the
      current situation in Spain regarding the management of elderly cancer patients
      through an online survey of medical oncologists. METHODS: A descriptive survey
      was sent to several hospitals by means of the SEOM website. A personal e-mail was
      also sent to SEOM members. RESULTS: Between March 2016 and April 2017, 154
      answers were collected. Only 74 centers (48%) had a geriatrics department and a
      mere 21 (14%) medical oncology departments had a person dedicated to GO. The vast
      majority (n = 135; 88%) had the perception that the number of elderly patients
      with cancer seen in clinical practice had increased. Eighteen (12%) oncologists
      had specific protocols and geriatric scales were used at 55 (31%) centers. Almost
      all (92%) claimed to apply special management practices using specific tools.
      There was agreement that GO afforded certain potential advantages. Finally, 99%
      of the oncologists surveyed believed it and that training in GO had to be
      improved. CONCLUSIONS: From the nationwide survey promoted by the Spanish
      Geriatric Oncology Working Group on behalf of SEOM, we conclude that there is
      currently no defined care structure for elderly cancer patients. There is an
      increasing perception of the need for training in GO. This survey reflects a
      reality in which specific needs are perceived.

PMID- 29327242
TI  - Self-assembly of magnetically functionalized star-polymer nano-colloids.
AB  - We explore the potential of star-polymers that carry super-paramagnetic nano
      particles as end-groups with respect to the single-molecule self-assembly
      process. With the aid of molecular dynamics simulation, the configurations of
      these macromolecules are analyzed as a function of functionality, magnetic
      interaction strength, and the length of the polymeric arms. By means of an
      external magnetic field the nano-particles can be controlled to form static or
      dynamic dipolar chains, resulting in conformations of isolated stars that can be
      characterized by the average number of chains and length. The single-molecule
      conformation diagram in the plane of magnetic interaction strength vs. the star
      functionality is obtained. Further, the molecules are characterized by means of
      various shape and size order parameters.

PMID- 29327241
TI  - A SUVmax-based propensity matched analysis of stereotactic body radiotherapy
      versus surgery in stage I non-small cell lung cancer: unveiling the role of 18F
      FDG PET/CT in clinical decision-making.
AB  - BACKGROUND: The value of maximum standard uptake value (SUVmax) was overlooked in
      current studies comparing stereotactic body radiotherapy (SBRT) versus surgery
      for stage I non-small cell lung cancer (NSCLC). Herein, we aimed to compare the 3
      year outcomes based on patients for whom SUVmax were available, and to explore
      the role of SUVmax in clinical decision-making. METHODS: From January 2010 to
      June 2016, data of eligible patients were collected. Patient variables and
      clinical outcomes were compared in both unmatched and matched groups using
      propensity score matching (PSM). Multivariate analysis was performed for
      predictors of poor outcome. The relationship between treatment approach and
      survival outcome was also evaluated in subgroup patients stratified by SUVmax
      level. RESULTS: A total of 425 patients treated with either surgery (325) or SBRT
      (100) were included. Patients receiving SBRT were significantly older, had a
      higher level of SUVmax and were more likely to have tumor of centrally located.
      Multivariate analysis showed that SUVmax and tumor size were significant
      predictors for 3-year OS, LRC, and PFS, while better PFS was also related to
      peripheral tumor and surgery. The result of PSM analysis also showed that
      compared to SBRT, surgery could only achieve better PFS. Subgroup analysis
      indicated that surgery had added advantage of 3-year LRC and PFS for patients in
      high SUVmax group (SUVmax > 8), but not in low SUVmax group. CONCLUSIONS: The
      study found a superior PFS after surgery while OS and LRC did not differ between
      SBRT and surgery. Surgery should be recommended for tumor of high SUVmax.

PMID- 29327243
TI  - Facile Synthesis of Wormhole-Like Mesoporous Tin Oxide via Evaporation-Induced
      Self-Assembly and the Enhanced Gas-Sensing Properties.
AB  - Wormhole-like mesoporous tin oxide was synthesized via a facile evaporation
      induced self-assembly (EISA) method, and the gas-sensing properties were
      evaluated for different target gases. The effect of calcination temperature on
      gas-sensing properties of mesoporous tin oxide was investigated. The results
      demonstrate that the mesoporous tin oxide sensor calcined at 400  degrees C
      exhibits remarkable selectivity to ethanol vapors comparison with other target
      gases and has a good performance in the operating temperature and
      response/recovery time. This might be attributed to their high specific surface
      area and porous structure, which can provide more active sites and generate more
      chemisorbed oxygen spices to promote the diffusion and adsorption of gas
      molecules on the surface of the gas-sensing material. A possible formation
      mechanism of the mesoporous tin oxide and the enhanced gas-sensing mechanism are
      proposed. The mesoporous tin oxide shows prospective detecting application in the
      gas sensor fields.

PMID- 29327246
TI  - Invited comment to: rates of and methods used at reoperation for recurrence after
      primary inguinal hernia repair with Prolene Hernia System and Lichtenstein.
      Magnusson J, Gustafsson UO, Nygren J, Thorell A.

PMID- 29327244
TI  - Antibody-based delivery of tumor necrosis factor (L19-TNFalpha) and interleukin-2
      (L19-IL2) to tumor-associated blood vessels has potent immunological and
      anticancer activity in the syngeneic J558L BALB/c myeloma model.
AB  - PURPOSE: To analyze the impact of TNFalpha or IL2 on human lymphocytes in vitro
      and the anti-tumor and immune-modifying effects of L19-IL2 and L19-TNFalpha on
      subcutaneously growing J558L myeloma in immunocompetent mice. METHODS: PBMCs from
      three healthy volunteers were incubated with IL2, TNFalpha, or with IL2 plus
      addition of TNFalpha (final 20 h). BALB/c J558L mice with subcutaneous tumors
      were treated with intravenous L19-TNFalpha plus L19-IL2, or controls. Tumor
      growth and intra- and peri-tumoral tissues were analyzed for micro-vessel
      density, necrosis, immune cell composition, and PD1 or PD-L1 expressing cells.
      RESULTS: Exposure of PBMC in vitro to IL2, TNFalpha, or to IL2 over 3 and 5 days
      plus TNFalpha for the final 20 h resulted in an approximately 50 and 75%
      reduction of the CD25low effector cell/CD25high Treg cell ratio, respectively,
      compared to medium control. IL2 or TNFalpha increased the proportion of CD4-
      CD25low effector lymphocytes while reducing the proportion of CD4+ CD25low Teff
      cells. In the J558L myeloma model, tumor eradication was observed in 58, 42, 25,
      and 0% of mice treated with L19-TNFalpha plus L19-IL2, L19-TNFalpha, L19-IL2, and
      PBS, respectively. L19-TNFalpha/L19-IL2 combination caused tumor necrosis,
      capillary density doubling, peri-tumoral T cell and PD1+ T cell reduction (-
      50%), and an increase in PD-L1+ myeloma cells. CONCLUSION: IL2, TNFalpha, or IL2
      plus TNFalpha (final 20 h) increased the proportion of CD4- CD25low effector
      lymphocytes possibly indicating immune activation. L19-TNFalpha/L19-IL2
      combination therapy eradicated tumors in J558L myeloma BALB/c mice likely via
      TNFalpha-induced tumor necrosis and L19-TNFalpha/L19-IL2-mediated local cellular
      immune reactions.

PMID- 29327245
TI  - High nuclear MSK1 is associated with longer survival in breast cancer patients.
AB  - PURPOSE: Mitogen- and stress-activated kinases (MSKs) are important substrates of
      the mitogen-activated protein kinase (MAPK)-activated protein kinase family. MSK1
      and MSK2 are both nuclear serine/threonine protein kinases, with MSK1 being
      suggested to potentially play a role in breast cancer cell proliferation, cell
      cycle progression, cell migration, invasion and tumour growth. The aim of the
      current study was to assess MSK1 protein expression in breast cancer tumour
      specimens, evaluating its prognostic significance. METHODS: A large cohort of
      1902 early stage invasive breast cancer patients was used to explore the
      expression of MSK1. Protein expression was examined using standard
      immunohistochemistry on tissue microarrays. RESULTS: Low MSK1 protein expression
      was associated with younger age (P = 0.004), higher tumour grade (P < 0.001),
      higher Nottingham Prognostic Index scores (P = 0.007), negative ER (P < 0.001)
      and PR (P < 0.001) status, and with triple-negative (P < 0.001) and basal-like (P
      < 0.001) phenotypes. Low MSK1 protein expression was significantly associated
      with shorter time to distant metastasis (P < 0.001), and recurrence (P = 0.013)
      and early death due to breast cancer (P = 0.01). This association between high
      MSK1 expression and improved breast cancer-specific survival was observed in the
      whole cohort (P = 0.009) and in the HER2-negative and non-basal like tumours (P =
      0.006 and P = 0.024, respectively). Multivariate analysis including other
      prognostic variables indicated that MSK1 is not an independent marker of outcome.
      CONCLUSIONS: High MSK1 is associated with improved breast cancer-specific
      survival in early stage invasive breast cancer patients, and has additional
      prognostic value in HER2-negative and non-basal like disease. Although not an
      independent marker of outcome, we believe such findings and significant
      associations with well-established negative prognostic factors (age, grade,
      Nottingham Prognostic Index, hormone receptor status, time to distant metastasis,
      recurrence and triple-negative/basal-like status) warrant further examination and
      validation in independent patient cohorts.

PMID- 29327247
TI  - Comparing different modalities for the diagnosis of incisional hernia: a
      systematic review.
AB  - PURPOSE: Incisional hernia (IH) is the most frequent complication after abdominal
      surgery. The diagnostic modality, observer, definition, and diagnostic protocol
      used for the diagnosis of IH potentially influence the reported prevalence. The
      objective of this systematic review is to evaluate the diagnostic accuracy of
      different modalities used to identify IH. METHODS: Embase, MEDLINE OvidSP, Web of
      Science, Google Scholar, and Cochrane databases were searched to identify studies
      diagnosing IH. Studies comparing the IH detection rate of two different
      diagnostic modalities or inter-observer variability of one modality were
      included. Quality assessment of studies was done by Cochrane Collaboration's
      tool. Article selection and data collection were performed independently by two
      researchers. PROSPERO registration: CRD42017062307. RESULTS: Fifteen studies
      representing a total of 2986 patients were included. Inter-observer variation for
      CT-scan ranged from 11.2 to 69% (n = 678). Disagreement between ultrasound and CT
      scan ranged between 6.6 and 17% (n = 221). Ten studies compared physical
      examination to CT-scan or ultrasound. Disagreement between physical examination
      and imaging ranged between 7.6 and 39% (n = 1602). Between 15 and 58% of IHs were
      solely detected by imaging (n = 483). Relative increase in IH prevalence for
      imaging compared to physical examination ranged from 0.92 to 2.4 (n = 1922).
      CONCLUSIONS: Ultrasound or CT-scan will result in substantial additional IH
      diagnosis. Lack of consensus regarding the definition of IH might contribute to
      the disagreement rates. Both the observer and diagnostic modality used could be
      additional factors explaining variability in IH prevalence and should be reported
      in IH research.

PMID- 29327249
TI  - Neuronal damage and abnormal contraction: Is the circle of synchronicity
      complete?

PMID- 29327250
TI  - Letter regarding "Meta-analysis of 18F-FDG PET/CT in the diagnosis of infective
      endocarditis".

PMID- 29327248
TI  - Introducing new technology safely into urological practice.
AB  - PURPOSE: Surgical innovation is necessary to ensure continued improvement in
      patient care. However, several challenges unique to the surgical craft are
      encountered during the development and validation of such new technology. This
      article highlights some of these challenges and gives an overview of existing
      solutions. METHODS: A Pubmed review was performed about the "introduction of new
      technology" to identify challenges. Cross-referencing was used to explore the
      possible solutions per challenge. RESULTS: Several characteristics of the
      surgical craft itself limit our ability to establish randomised controlled trials
      and hence provide clear categorical evidence. Existing certification bodies for
      new technology often use unstructured regulations and allow fast-track bypassing
      systems. Consequently the IDEAL framework (innovation, development, exploration,
      assessment, long-term follow-up) proposes an objective scientific approach whilst
      defining stakeholder responsibilities. The selection of which new modality to
      implement is heavily influenced by third parties unrelated to the best patient
      outcomes and thus professional organisations can aid in this decision-making.
      Appropriate training of surgeons and their teams until proficiency is achieved is
      essential prior to credentialling. Finally long-term surveillance of outcomes in
      the form of registries is an increasing responsibility of the urological
      community to maintain our role in directing the adoption or rejection of these
      innovations. CONCLUSION: Urological innovation is a dynamic and challenging
      process. Increasing efforts are identified within the urological community to
      render the process more reliable and transparent.

PMID- 29327251
TI  - A practical method to reduce breast attenuation during SPECT myocardial perfusion
      imaging.

PMID- 29327252
TI  - Compared vulnerabilities to small cardiac motions between different cameras used
      for myocardial perfusion imaging.
AB  - : This phantom-based study was aimed to determine whether cardiac CZT-cameras,
      which provide an enhanced spatial resolution and image contrast compared to Anger
      cameras, are similarly affected by small cardiac motions. Translations of a left
      ventricular (LV) insert at half-SPECT acquisitions through six possible
      orthogonal directions and with 5- or 10-mm amplitude were simulated on the
      Discovery NM-530c and DSPECT CZT-cameras and on an Anger Symbia T2 camera
      equipped with an astigmatic (IQ.SPECT) or conventional parallel-hole collimator
      (Conv.SPECT). SPECT images were initially reconstructed as currently recommended
      for clinical routine. The heterogeneity in recorded activity from the 17 LV
      segments gradually increased between baseline and motions simulated at 5- and 10
      mm amplitudes with all cameras, although being higher for Anger- than CZT-cameras
      at each step and resulting in a higher mean number of artifactual abnormal
      segments (at 10-mm amplitude, Conv. SPECT: 3.7; IQ. SPECT: 1.8, Discovery: 0.7,
      DSPECT: 0). However, this vulnerability to motion was markedly (1) decreased for
      Conv.SPECT reconstructed without the recommended Resolution Recovery algorithm
      and (2) increased for DSPECT reconstructed without the recommended cardiac model.
      CZT-cameras and especially the DSPECT appear less vulnerable to small cardiac
      motions than Anger-cameras although these differences are strongly dependent on
      reconstruction parameters.

PMID- 29327253
TI  - My warranty has expired: I need to be retested.
AB  - The concept of warranty period, the duration of time during which the patient's
      risk remains low, is appealing. However, some points remain to be resolved before
      its translation in the clinical arena. Methodological issues should be
      standardized in order to compare the results of studies in different patient
      populations. Also, the definition of a "normal" study should always take into
      consideration the history of prior revascularization, the achieved level of
      exercise, and the stressor used. The promise of warranty can be questioned by the
      patient's baseline demographic and clinical characteristics and may also be
      influenced by life-style modification in the course of the follow-up. The
      "warranty period" concept should shift from data reflecting the time to a cardiac
      event to the development of ischemia, given an opportunity for intervention
      before a cardiac event occurs. In this context, clarify the role of serial
      imaging can be extremely useful, in particular to evaluate if and when retesting
      a patient after a normal scan.

PMID- 29327254
TI  - Abnormal myocardial perfusion pattern in the absence of significant coronary
      artery stenosis.

PMID- 29327255
TI  - Gallium-68 DOTANOC scan in a patient with suspected cardiac sarcoidosis.

PMID- 29327256
TI  - Targeting atrial fibrillation promoting atrial structural remodeling: is this a
      viable strategy in patients with heart failure?

PMID- 29327257
TI  - Biomechanical Characterisation of Bone-anchored Implant Systems for Amputation
      Limb Prostheses: A Systematic Review.
AB  - Bone-anchored limb prostheses allow for the direct transfer of external loads
      from the prosthesis to the skeleton, eliminating the need for a socket and the
      associated problems of poor fit, discomfort, and limited range of movement. A
      percutaneous implant system for direct skeletal attachment of an external limb
      must provide a long-term, mechanically stable interface to the bone, along with
      an infection barrier to the external environment. In addition, the mechanical
      integrity of the implant system and bone must be preserved despite constant
      stresses induced by the limb prosthesis. Three different percutaneous implant
      systems for direct skeletal attachment of external limb prostheses are currently
      clinically available and a few others are under investigation in human subjects.
      These systems employ different strategies and have undergone design changes with
      a view to fulfilling the aforementioned requirements. This review summarises such
      strategies and design changes, providing an overview of the biomechanical
      characteristics of current percutaneous implant systems for direct skeletal
      attachment of amputation limb prostheses.

PMID- 29327258
TI  - Mental health problems of Syrian refugee children: the role of parental factors.
AB  - War-torn children are particularly vulnerable through direct trauma exposure as
      well through their parents' responses. This study thus investigated the
      association between trauma exposure and children's mental health, and the
      contribution of parent-related factors in this association. A cross-sectional
      study with 263 Syrian refugee children-parent dyads was conducted in Turkey. The
      Stressful Life Events Questionnaire (SLE), General Health Questionnaire,
      Parenting Stress Inventory (PSI-SF), Impact of Events Scale for Children (CRIES
      8), and Strengths and Difficulties Questionnaire were used to measure trauma
      exposure, parental psychopathology, parenting-related stress, children's post
      traumatic stress symptoms (PTSS), and mental health problems, respectively.
      Trauma exposure significantly accounted for unique variance in children's PTSS
      scores. Parental psychopathology significantly contributed in predicting
      children's general mental health, as well as emotional and conduct problems,
      after controlling for trauma variables. Interventions need to be tailored to
      refugee families' mental health needs. Trauma-focused interventions should be
      applied with children with PTSD; whilst family-based approaches targeting
      parents' mental health and parenting-related stress should be used in conjunction
      with individual interventions to improve children's comorbid emotional and
      behavioural problems.

PMID- 29327259
TI  - 5-Aminolevulinic Acid-Squalene Nanoassemblies for Tumor Photodetection and
      Therapy: In Vitro Studies.
AB  - Protoporphyrin IX (PpIX) as natural photosensitizer derived from administration
      of 5-aminolevulinic acid (5-ALA) has found clinical use for photodiagnosis and
      photodynamic therapy of several cancers. However, broader use of 5-ALA in
      oncology is hampered by its charge and polarity that result in its reduced
      capacity for passing biological barriers and reaching the tumor tissue. Advanced
      drug delivery platforms are needed to improve the biodistribution of 5-ALA. Here,
      we report a new approach for the delivery of 5-ALA. Squalenoylation strategy was
      used to covalently conjugate 5-ALA to squalene, a natural precursor of
      cholesterol. 5-ALA-SQ nanoassemblies were formed by self-assembly in water. The
      nanoassemblies were monodisperse with average size of 70 nm, polydispersity index
      of 0.12, and zeta-potential of + 36 mV. They showed good stability over several
      weeks. The drug loading of 5-ALA was very high at 26%. In human prostate cancer
      cells PC3 and human glioblastoma cells U87MG, PpIX production was monitored in
      vitro upon the incubation with nanoassemblies. They were more efficient in
      generating PpIX-induced fluorescence in cancer cells compared to 5-ALA-Hex at 1.0
      to 3.3 mM at short and long incubation times. Compared to 5-ALA, they showed
      superior fluorescence performance at 4 h which was diminished at 24 h. 5-ALA-SQ
      presents a novel nano-delivery platform with great potential for the systemic
      administration of 5-ALA.

PMID- 29327260
TI  - Lifetime study in mice after acute low-dose ionizing radiation: a multifactorial
      study with special focus on cataract risk.
AB  - Because of the increasing application of ionizing radiation in medicine,
      quantitative data on effects of low-dose radiation are needed to optimize
      radiation protection, particularly with respect to cataract development. Using
      mice as mammalian animal model, we applied a single dose of 0, 0.063, 0.125 and
      0.5 Gy at 10 weeks of age, determined lens opacities for up to 2 years and
      compared it with overall survival, cytogenetic alterations and cancer
      development. The highest dose was significantly associated with increased body
      weight and reduced survival rate. Chromosomal aberrations in bone marrow cells
      showed a dose-dependent increase 12 months after irradiation. Pathological
      screening indicated a dose-dependent risk for several types of tumors.
      Scheimpflug imaging of the lens revealed a significant dose-dependent effect of
      1% of lens opacity. Comparison of different biological end points demonstrated
      long-term effects of low-dose irradiation for several biological end points.

PMID- 29327262
TI  - Risk of Neoplastic Progression Among Patients with an Irregular Z Line on Long
      Term Follow-Up.
AB  - BACKGROUND: Barrett's esophagus (BE) is a known complication of gastroesophageal
      reflux disease. In a previous study, we described a high prevalence of intestinal
      metaplasia (IM) in patients with an irregular Z line. However, the clinical
      importance of this finding is unclear. GOALS: To evaluate the long-term
      development of BE and relevant complications in patients diagnosed with an
      irregular Z line, with or without IM, on routine esophago-gastro-duodenoscopy
      (EGD). METHODS: In our previously described cohort, 166 out of 2000 consecutive
      patients were diagnosed with an incidental irregular Z line. Of those with
      irregular Z line, 43% had IM. In this continuation study, patients' status was
      reassessed after a median follow-up of 70 months. Patients were divided into two
      groups: Patients with IM (IM-positive group) and without IM (IM-negative group).
      The incidence of long-term development of BE, dysplasia, and esophageal
      adenocarcinoma were compared between groups. RESULTS: At least one follow-up EGD
      was performed in 102 (61%) patients with an irregular Z line. Endoscopic evidence
      of BE was found in eight IM-positive patients (8/50 [16%]) and in one IM-negative
      patient (1/52 [1.9%]). Two (4%) IM-positive patients developed BE with low-grade
      dysplasia. None of the patients developed high-grade dysplasia, or esophageal
      adenocarcinoma. CONCLUSIONS: Patients with irregular Z line do not develop major
      BE complication in more than 5 years of follow-up.

PMID- 29327261
TI  - Chronic Rejection After Intestinal Transplant: Where Are We in Order to Avert It?
AB  - Chronic rejection affects the long-term survival of all solid organ transplants
      and, among intestinal allografts, occurs in up to 10% of the recipients. The
      insidious clinical evolution of the chronic allograft enteropathy, the absence of
      noninvasive biomarkers, and the late endoscopic findings delay its diagnosis. No
      pharmacological approach has been proven effective, and allograft removal
      nowadays still represents the only available therapy. The inclusion of the liver
      in the visceral allograft appears to be the only intervention affecting the
      development of chronic rejection, as revealed by large-center studies and
      registry reports. A significant body of evidence emerged from the experimental
      setting and provided essential knowledge on the complex mechanisms behind the
      development of chronic allograft enteropathy. More recently, donor-specific
      antibodies have been suggested as an early, key element in the natural history of
      chronic allograft enteropathy and several novel approaches, tackling the antibody
      mediated graft injury, have gained acceptance in clinical settings and are
      believed to impact on chronic rejection. The inclusion of a liver allograft is
      advocated when re-transplanting a sensitized recipient, due to its protective
      effect against humoral immunity. Multicenter trials are required to understand
      and tackle chronic rejection, and find the therapeutic answer to this clinical
      dilemma.

PMID- 29327264
TI  - Inline UV/Vis spectroscopy as PAT tool for hot-melt extrusion.
AB  - Hot-melt extrusion on co-rotating twin screw extruders is a focused technology
      for the production of pharmaceuticals in the context of Quality by Design. Since
      it is a continuous process, the potential for minimizing product quality
      fluctuation is enhanced. A typical application of hot-melt extrusion is the
      production of solid dispersions, where an active pharmaceutical ingredient (API)
      is distributed within a polymer matrix carrier. For this dosage form, the product
      quality is related amongst others to the drug content. This can be monitored on-
      or inline as critical quality attribute by a process analytical technology (PAT)
      in order to meet the specific requirements of Quality by Design. In this study,
      an inline UV/Vis spectrometer from ColVisTec was implemented in an early
      development twin screw extruder and the performance tested in accordance to the
      ICH Q2 guideline. Therefore, two API (carbamazepine and theophylline) and one
      polymer matrix (copovidone) were considered with the main focus on the
      quantification of the drug load. The obtained results revealed the suitability of
      the implemented PAT tool to quantify the drug load in a typical range for
      pharmaceutical applications. The effort for data evaluation was minimal due to
      univariate data analysis, and in combination with a measurement frequency of 1
      Hz, the system is sufficient for real-time data acquisition.

PMID- 29327263
TI  - Proton Pump Inhibitors Increase the Susceptibility of Mice to Oral Infection with
      Enteropathogenic Bacteria.
AB  - BACKGROUND AND AIMS: Proton pump inhibitors (PPIs) are among the most frequently
      prescribed medications. Side effects including an increased risk of intestinal
      infections have been reported. It is assumed that PPIs can increase
      susceptibility to enteropathogens; however, the underlying mechanisms are
      unknown. Here in this study, we explored whether Lansoprazole (Laz), one of the
      PPIs, increases the susceptibility to enteropathogens, and further investigated
      the mechanism of it. METHODS: Mice were administered Laz intraperitoneally once
      daily and orally infected with Citrobacter rodentium (C. rodentium). The
      establishment of intestinal infection was assessed by histology and inflammatory
      cytokine expression levels measured by quantitative PCR. To test whether Laz
      changes the intestinal environment to influence the susceptibility, intestinal
      pH, microbiota, metabolites and immune cell distributions were evaluated via pH
      measurement, 16S rRNA gene sequencing, metabolome, and flow cytometry analyses
      after Laz administration. RESULTS: Colitis was induced with less C. rodentium in
      Laz-treated mice as compared with the controls. We found that increased numbers
      of C. rodentium could reach the cecum following Laz administration. Laz increased
      pH in the stomach but not in the intestines. It induced dysbiosis and changed the
      metabolite content of the small intestine. However, these changes did not lead to
      alterations of immune cell distribution. CONCLUSIONS: Laz raised susceptibility
      to C. rodentium as increased numbers of the pathogen reach the site of infection.
      Our results suggest that it was due to increased stomach pH which allowed more
      peroral enteropathogens to pass the stomach, but not because of changes of
      intestinal environment.

PMID- 29327265
TI  - Successful diagnosis of an occult fallopian tube carcinoma detected from the
      diaphragm metastasis.
AB  - We herein reported a rare case of an occult fallopian tube carcinoma first
      detected from the diaphragm metastasis. An 83-year-old woman who had a 30-mm
      tumor on the right diaphragm underwent radical resection. Pathologically, the
      tumor was diagnosed as a high-grade serous adenocarcinoma, suggesting metastasis
      from the pelvic visceral carcinoma. Although the primary site could not be
      detected by imaging examinations, laparoscopy revealed multiple peritoneal
      disseminations; therefore, total hysterectomy was performed. Finally, microscopic
      tumor invasion into the right fimbriae of the fallopian tube was found. A precise
      and detailed pathological and immunohistochemical examinations of the resected
      metastatic diaphragm tumor helped us obtain a proper diagnosis of the primary
      lesion and treat the patient appropriately. Since it is difficult to diagnose
      diaphragm tumors before surgery based on the anatomy, surgical options have
      played an important role in their treatment and diagnosis clinically.

PMID- 29327266
TI  - Social targets improve body-based and environment-based strategies during spatial
      navigation.
AB  - Encoding the position of another person in space is vital for everyday life.
      Nevertheless, little is known about the specific navigational strategies
      associated with encoding the position of another person in the wider spatial
      environment. We asked two groups of participants to learn the location of a
      target (person or object) during active navigation, while optic flow information,
      a landmark, or both optic flow information and a landmark were available in a
      virtual environment. Whereas optic flow information is used for body-based
      encoding, such as the simulation of motor movements, landmarks are used to form
      an abstract, disembodied representation of the environment. During testing, we
      passively moved participants through virtual space, and compared their abilities
      to correctly decide whether the non-visible target was before or behind them.
      Using psychometric functions and the Bayes Theorem, we show that both groups
      assigned similar weights to body-based and environment-based cues in the
      condition, where both cue types were available. However, the group who was
      provided with a person as target showed generally reduced position errors
      compared to the group who was provided with an object as target. We replicated
      this effect in a second study with novel participants. This indicates a social
      advantage in spatial encoding, with facilitated processing of both body-based and
      environment-based cues during spatial navigation when the position of a person is
      encoded. This may underlie our critical ability to make accurate distance
      judgments during social interactions, for example, during fight or flight
      responses.

PMID- 29327267
TI  - Antimicrobial peptide gene BdPho responds to peptidoglycan infection and mating
      stimulation in oriental fruit fly, Bactrocera dorsalis (Hendel).
AB  - Phormicins belong to defensin family, which are important antimicrobial peptides
      (AMPs) in insects. These AMPs are inducible upon challenging by immune triggers.
      In the present study, we identified the cDNA of a phormicin gene (BdPho) in the
      oriental fruit fly, Bactrocera dorsalis (Hendel), a ruinous agricultural pest
      causing great economic losses to fruits and vegetables. The cDNA of BdPho
      contains a 282 bp open reading frame encoding 93 amino acid residues, and the
      predicted molecular weight and isoelectric point of BdPho peptide were 9.83 kDa
      and 7.54, respectively. Quantitative real-time PCR analyses showed that the
      transcription level of BdPho was the highest in adult during different
      developmental stages and was the highest in abdomen among adult tagmata.
      Moreover, BdPho was highly expressed in fat body among different tissues, both in
      female and male adult. The mRNA level of BdPho was significantly up-regulated to
      7.46- and 14.53-fold at 3 and 6 h after the insects were challenged with
      peptidoglycans from Escherichia coli (PGN-EB), respectively, suggesting its
      antimicrobial activity against Gram-negative microorganisms. Furthermore, the
      expression level of BdPho was significantly up-regulated to 3.83-fold after
      mating, suggesting that female adults might enhance their immunity by up
      regulating the expression level of BdPho during mating. These results firstly
      describe the basic properties of the phormicin gene from B. dorsalis, and lay the
      foundation for investigating functional properties of AMPs and exploring the
      molecular mechanisms in the immune system.

PMID- 29327268
TI  - Serum thiol levels and thiol/disulphide homeostasis in gunshot injuries.
AB  - BACKGROUND: Gunshot injuries result in serious traumatic tissue damage due to
      high velocity of the bullet, deep penetration, and ballistic effect. Trauma is
      known to be related with oxidative stress. Serum thiol levels and
      disulphide/thiol homeostasis are novel oxidative stress biomarkers. In this
      study, we aimed to investigate serum thiol levels and disulphide/thiol
      homeostasis in injury patterns of patients admitted to the emergency department
      with a gunshot injury. METHOD: A total of 128 participants were included in the
      study. The participants were divided into two groups: the patient group (Group 1;
      n = 73) and healthy controls (Group 2; n = 55). Native thiol, total thiol,
      disulphide levels, disulphide/native thiol, disulphide/total thiol, and
      neutrophil-to-lymphocyte ratio (NLR) were measured. The Revised Trauma Scale
      (RTS) and Glasgow Coma Scale (GCS) scores were calculated. RESULTS: Native thiol,
      total thiol, and disulphide levels were significantly lower in Group 1 (p <
      0.001). Disulphide/native thiol ratio, disulphide/total thiol ratio, and NLR were
      significantly higher in Group 1, compared to Group 2 (p < 0.05). There was a
      positive correlation between thiol levels and RTS and GCS scores and NLR.
      Stepwise linear regression analysis showed that native thiol was an independent
      indicator of RTS and GCS scores. The receiver operating characteristic curve
      (ROC) analysis revealed that serum native thiol levels of <= 342.9 could predict
      gunshot injury with a sensitivity of 82% and a specificity of 77% (area under the
      curve = 0.853; 95% confidence interval 0.783-0.924). CONCLUSION: Our study
      results suggest that thiol-disulphide homeostasis is disrupted in patients
      sustaining gunshot injuries, and thiol levels decrease in correlation with the
      severity of trauma with a high sensitivity and specificity. As the level of
      native thiol is an independent predictor of the severity of trauma, reduced thiol
      levels may be of prognostic value in the early assessment of patients in the
      emergency room.

PMID- 29327270
TI  - [Paraneoplastic syndromes].

PMID- 29327269
TI  - Unfair Treatment and Periodontitis Among Adults in the Hispanic Community Health
      Study/Study of Latinos (HCHS/SOL).
AB  - This study investigates how perceived unfair treatment, towards self and observed
      towards others due to ethnicity, is associated with periodontitis among diverse
      Hispanic/Latino adults, accounting for sociodemographic, health behavior, and
      acculturation factors. Baseline (2008-2011) dental and survey data from the
      Hispanic Community Health Study/Study of Latinos (HCHS/SOL), a multicenter
      epidemiologic study, were analyzed (N = 12,750). Crude and adjusted prevalence
      ratios and confidence limits were estimated. Half (49%) reported never being
      treated unfairly, while 41% reported they were sometimes, and 10% reported it
      often/always. One third (32%) never saw others treated unfairly, while 42%
      reported it sometimes, and 26% reported it often/always. In the final fully
      adjusted model, the prevalence of periodontitis was higher among adults who were
      as follows: non-Dominican, older, male, had a past year dental visit, current and
      former smokers, and among those who observed unfair treatment towards others.
      Lower prevalence was associated with higher income, higher educational
      attainment, less than full-time employment, reporting experiencing unfair
      treatment, higher acculturation scores, and having health insurance. Perceived
      unfair treatment towards self was negatively associated with periodontitis
      prevalence, while observed unfair treatment towards others was positively
      associated with the outcome among diverse Hispanics/Latinos. The associations
      between unfair treatment and periodontitis warrant further exploration.

PMID- 29327271
TI  - [Paraneoplastic neurological syndromes : A current summary].
AB  - BACKGROUND: Paraneoplastic neurological syndromes (PNNS) are remote effects of a
      tumor and mediated by an altered immune reaction. In the last ten years, the
      spectrum of PNNS has changed profoundly with the discovery of a new category of
      neurological diseases that are associated with antibodies against surface or
      synaptic antigens. In contrast to classical PNNS, patients with surface receptor
      autoimmunity are often highly responsive to immunotherapy. OBJECTIVES: This
      article provides an update on the most relevant PNNS, focusing on specific
      syndromes associated with antibodies against classical onconeuronal antigens as
      well as surface and synaptic proteins. RESULTS: Classical PNNS are associated
      with antibodies against intracellular antigens (onconeuronal antibodies). They
      usually precede the tumor diagnosis and lead to the detection of the neoplasm.
      Affected patients are often older and have an unfavorable prognosis. Patients
      with surface receptor autoimmunity can have a similar presentation as classical
      PNNS; however, the disease is not necessarily triggered by a tumor and patients
      usually show a good response to treatment. Some surface receptor antibodies might
      manifest in highly characteristic syndromes and the resulting disease is named
      after the antibody, such as in anti-N-methyl-D-aspartate receptor (NMDAR)
      encephalitis. Other antibodies have considerable overlap in their clinical
      presentation and may be difficult to distinguish, such as in limbic encephalitis
      associated with GABA(B)R and alpha-amino-3-hydroxy-5-hydroxy-5-methyl-4
      isoxazolpropionsaure receptor (AMPAR) antibodies. The diagnosis of the PNNS is
      important for an early recognition of a tumor and prompt initiation of treatment,
      which is associated with a better outcome of patients.

PMID- 29327272
TI  - Protein Losing Enteropathy in Hennekam Syndrome.

PMID- 29327273
TI  - Chronic Gastric Volvulus: Cause of Feed Intolerance.

PMID- 29327274
TI  - First-line therapy for advanced non-small cell lung cancer with activating EGFR
      mutation: is combined EGFR-TKIs and chemotherapy a better choice?
AB  - As the standard first-line treatment for advanced non-small cell lung cancer
      (NSCLC) with activating epidermal growth factor receptor (EGFR) mutation, EGFR
      tyrosine kinase inhibitors (EGFR-TKIs) have significantly improved the median
      progression-free survival (PFS) up to 18.9 months. However, almost all patients
      eventually develop acquired resistance to EGFR-TKIs, which limits the first-line
      PFS. To overcome the resistance and improve overall survival, researchers have
      tried to identify the resistance mechanisms and develop new treatment strategies,
      among which a combination of EGFR-TKIs and cytotoxic chemotherapy is one of the
      hotspots. The data from preclinical and clinical studies on combined EGFR-TKIs
      and chemotherapy have shown very interesting results. Here, we reviewed the
      available preclinical and clinical studies on first-line EGFR-TKIs-chemotherapy
      combination in patients with advanced NSCLC harboring activating EGFR mutation,
      aiming to provide evidences for more potential choices and shed light on clinical
      treatment.

PMID- 29327275
TI  - [Eyelid surgery : Principles of blepharoplasty, application of CO2 lasers,
      aftercare and scar revision].

PMID- 29327277
TI  - Association between remifentanil and acute kidney injury.

PMID- 29327276
TI  - Portal congestion and intestinal edema in hospitalized patients with heart
      failure.
AB  - An interaction between the intestine and cardiovascular disease has been
      suggested. We thought to clarify the association between intestinal conditions
      and clinical outcomes in patients with heart failure (HF). Hemodynamic parameters
      in intestinal vessels [superior mesenteric artery (SMA), inferior mesenteric
      artery (IMA), and portal vein (PV)] and average colon wall thickness (aCWT) from
      the ascending colon to sigmoid colon were evaluated in 224 hospitalized HF
      patients. Echocardiographic parameters and composite event rates (all-cause
      mortality, readmission for HF deterioration, major ventricular arrhythmias) were
      also examined. Higher PV congestion index (CI) and aCWT were observed in patients
      with New York Heart Association (NYHA) class III/IV. Higher PVCI [hazard ratio
      (HR) per + 1 standard deviation (SD) 1.50, p < 0.01] and aCWT (HR per + 1 SD
      1.45, p < 0.01) were independently associated with higher composite event rates
      during the follow-up of 122 +/- 68 days. None of SMA/IMA hemodynamic parameters
      were associated with NYHA class or composite event rates. Higher right
      ventricular end-diastolic dimension (38 +/- 7 vs 34 +/- 9 mm, p < 0.01) and lower
      tricuspid annual plane systolic excursion (15 +/- 5 vs 19 +/- 5 mm, p < 0.001)
      were observed in patients with higher PVCI (> 0.031 cm s) and aCWT (> 2.8 mm)
      relative to those in others. In conclusion, increased portal congestion and
      intestinal edema were associated with severe HF symptoms and poor outcomes in
      hospitalized HF patients, in addition to being associated with impaired right
      sided cardiac function.

PMID- 29327278
TI  - Nicotinamide Inhibits Ethanol-Induced Caspase-3 and PARP-1 Over-activation and
      Subsequent Neurodegeneration in the Developing Mouse Cerebellum.
AB  - Fetal alcohol spectrum disorder (FASD) is the principal preventable cause of
      mental retardation in the western countries resulting from alcohol exposure
      during pregnancy. Ethanol-induced massive neuronal cell death occurs mainly in
      immature neurons during the brain growth spurt period. The cerebellum is one of
      the brain areas that are most sensitive to ethanol neurotoxicity. Currently,
      there is no effective treatment that targets the causes of these disorders and
      efficient treatments to counteract or reverse FASD are desirable. In this study,
      we investigated the effects of nicotinamide on ethanol-induced neuronal cell
      death in the developing cerebellum. Subcutaneous administration of ethanol in
      postnatal 4-day-old mice induced an over-activation of caspase-3 and PARP-1
      followed by a massive neurodegeneration in the developing cerebellum.
      Interestingly, treatment with nicotinamide, immediately or 2 h after ethanol
      exposure, diminished caspase-3 and PARP-1 over-activation and reduced ethanol
      induced neurodegeneration. Conversely, treatment with 3-aminobenzadine, a
      specific PARP-1 inhibitor, was able to completely block PARP-1 activation, but
      not caspase-3 activation or ethanol-induced neurodegeneration in the developing
      cerebellum. Our results showed that nicotinamide reduces ethanol-induced neuronal
      cell death and inhibits both caspase-3 and PARP-1 alcohol-induced activation in
      the developing cerebellum, suggesting that nicotinamide might be a promising and
      safe neuroprotective agent for treating FASD and other neurodegenerative
      disorders in the developing brain that shares similar cell death pathways.

PMID- 29327279
TI  - Emotion Recognition and Psychological Comorbidity in Friedreich's Ataxia.
AB  - Friedreich's ataxia (FRDA) is an autosomal recessive disease presenting with
      ataxia, corticospinal signs, peripheral neuropathy, and cardiac abnormalities.
      Little effort has been made to understand the psychological and emotional burden
      of the disease. The aim of our study was to measure patients' ability to
      recognize emotions using visual and non-verbal auditory hints, and to correlate
      this ability with psychological, neuropsychological, and neurological variables.
      We included 20 patients with FRDA, and 20 age, sex, and education matched healthy
      controls (HC). We measured emotion recognition using the Geneva Emotion
      Recognition Test (GERT). Neuropsychological status was assessed measuring memory,
      executive functions, and prosopagnosia. Psychological tests were Patient Health
      Questionnaire-9 (PHQ-9), State Trait Anxiety Inventory-state/-trait (STAI-S/-T),
      and Structured Clinical Interview for DSM Disorders II. FRDA patients scored
      worse at the global assessment and showed impaired immediate visuospatial memory
      and executive functions. Patients presented lower STAI-S scores, and similar
      scores at the STAI-T, and PHQ-9 as compared to HC. Three patients were identified
      with personality disorders. Emotion recognition was impaired in FRDA with 29%
      reduction at the total GERT score (95% CI - 44.8%, - 12.6%; p < 0.001; Cohen's d
      = 1.2). Variables associated with poor GERT scores were the 10/36 spatial recall
      test, the Ray Auditory Verbal Learning Test, the Montreal Cognitive Assessment,
      and the STAI-T (R2 = 0.906; p < 0.001). FRDA patients have impaired emotion
      recognition that may be secondary to neuropsychological impairment. Depression
      and anxiety were not higher in FRDA as compared to HC and should not be
      considered as part of the disease.

PMID- 29327280
TI  - Comparison of the DING protein from the archaeon Sulfolobus solfataricus with
      human phosphate-binding protein and Pseudomonas fluorescence DING counterparts.
AB  - DING proteins represent a new group of 40 kDa-related members, ubiquitous in
      living organisms. The family also include the DING protein from Sulfolobus
      solfataricus, functionally related to poly(ADP-ribose) polymerases. Here, the
      archaeal protein has been compared with the human Phosphate-Binding Protein and
      the Pseudomonas fluorescence DING enzyme, by enzyme assays and immune cross
      reactivity. Surprisingly, as the Sulfolobus enzyme, the Human and Pseudomonas
      proteins display poly(ADP-ribose) polymerase activity, whereas a phosphatase
      activity was only present in Sulfolobus and human protein, despite the conserved
      phosphate-binding site residues in Pseudomonas DING. All proteins were positive
      to anti-DING antibodies and gave a comparable pattern of anti-poly(ADP-ribose)
      polymerase immunoreactivity with two bands, at around 40 kDa and roughly at the
      double of this molecular mass. The latter signal was present in all Sulfolobus
      enzyme preparations and proved not due to either a contaminant or a precursor
      protein, but likely being a dimeric form of the 40 kDa polypeptide. The common
      immunological and partly enzymatic behavior linking human, Pseudomonas and
      Sulfolobus DING proteins, makes the archaeal protein an important model system to
      investigate DING protein function and evolution within the cell.

PMID- 29327281
TI  - Effect of early natal supplementation of paracetamol on attenuation of
      exotoxin/endotoxin induced pyrexia and precipitation of autistic like features in
      albino rats.
AB  - The present study was aimed to test the hypothesis that paracetamol (PCM) can
      precipitate autistic like features when used to counteract vaccine-induced fever
      using experimental rat pups. The pups were treated with measles mumps rubella
      (MMR) vaccine, diphtheria tetanus and pertussis (DPT) vaccines and
      lipopolysaccharide (LPS) with subsequent PCM treatment. The pups were evaluated
      for postnatal growth (weight gain, eye opening) and behavior alterations
      (swimming performance, olfactory discrimination, negative geotaxis, nociception,
      and locomotor activity) by performing battery of neurobehavioral test.
      Significant correlation was observed between social behavioral domains
      (nociception, anxiety and motor coordination) and pro-inflammatory load in the
      pups when treated with MMR/LPS along with PCM. A significant change in pro and
      anti-inflammatory (IL-4, IL-6, IL-10) markers were observed in rats treated with
      PCM, MMR, LPS, DPS alone or in combination with MMR, LPS and DPT (5128.6 +/-
      0.000, 15,488 +/- 0.000***, 9661.1 +/- 157.29***a, 15,312 +/- 249.29***, 10,471
      +/- 0.00***a, 16,789 +/- 273.34*** and 12,882 +/- 0.00***a). Pups were also
      scrutinized for the markers of oxidative stress, inflammation and
      histopathologically. All the treatment groups showed significant alteration in
      the behavioral changes, oxidative markers (TBARS-in control-4.33 +/- 0.02, PCM
      9.42 +/- 0.18***, MMR-5.27 +/- 0.15***, MMR + PCM-8.57 +/- 0.18*** a, LPS-6.84 +/
      0.10***, LPS + PCM-4.51 +/- 0.30***a, DPT-5.68 +/- 0.12***, DPT + PCM-7.26 +/-
      0.18***a) and inflammatory markers without following any specific treatment.
      These observation could be accorded to variable phenotypes of autistic spectrum
      disorders (ASDs).

PMID- 29327283
TI  - Persea americana Mill. crude extract exhibits antinociceptive effect on UVB
      radiation-induced skin injury in mice.
AB  - Persea americana, popularly known as avocado, has been empirically used as
      analgesic and anti-inflammatory including in the skin disorder treatment. Species
      of the genus Persea also show a photoprotective effect against UVB radiation. We
      investigated the antinociceptive and anti-inflammatory effects from a topical
      formulation containing the P. americana leaf extract in a UVB irradiation-induced
      burn model in mice and performed a gel-formulation stability study. The
      antinociceptive and anti-inflammatory effect was evaluated through mechanical
      allodynia, paw oedema, and inflammatory cell infiltration. Phenolic compounds
      were quantified by UHPLC-MS/MS. The gel-formulation stability study was performed
      analyzing organoleptic characteristics, pH, and viscosity. P. americana (3%) gel
      was able to prevent the UVB irradiation-induced mechanical allodynia on the 2nd
      and 3rd day after irradiation with maximum inhibition of 60 +/- 12% at 2nd day.
      Such effect may be attributed, at least in part, due the presence of (+)-catechin
      (302.2 +/- 4.9 MUg/g) followed by chlorogenic acid (130 +/- 5.1 MUg/g) and rutin
      (102.4 +/- 0.9 MUg/g) found in the extract. The gel was not able to prevent the
      inflammatory parameters such as edema and leukocyte infiltration induced by UVB
      irradiation. No changes important were detected in the stability study, mainly in
      low temperature. Our results suggest that P. americana gel-formulation, which
      presented stability, ensuring its quality and the therapeutic effect, could be an
      interesting strategy for the treatment of the pain associated with sunburn; this
      effect could be attributed to its biological constituents, especially catechin,
      chlorogenic acid, and rutin.

PMID- 29327282
TI  - Ziziphus spina-christi leaf extract pretreatment inhibits liver and spleen injury
      in a mouse model of sepsis via anti-oxidant and anti-inflammatory effects.
AB  - Sepsis is a systemic response to infection that can result in acute hepatic and
      splenic damage. Ziziphus spina-christi (L.) is a wild tree used as a medicinal
      plant by ancient Egyptians. However, little is known about the mechanism
      underlying its effects on sepsis. The current study investigated the protective
      effects of a Z. spina-christi leaf extract (ZSCLE) on liver and spleen damage in
      a male C57BL/6 mouse model of sepsis, induced by cecal ligation and puncture
      (CLP). Prior to CLP, ZSCLE was administered daily for five consecutive days via
      oral gavage at doses of 100, 200, or 300 mg/kg. The mice were euthanized 9 h
      after CLP, and oxidative stress markers were measured (myeloperoxidase, lipid
      peroxidation, nitric oxide, and reduced glutathione). In addition, we
      investigated histological changes, anti-oxidant enzyme activities (superoxide
      dismutase, catalase, glutathione peroxidase, and glutathione reductase), cytokine
      levels, protein expression of nuclear factor-kappaB and inducible nitric oxide
      synthase (iNOS), and mRNA levels of mitogen-activated protein kinase (8, 9, and
      14), iNOS, tumor necrosis factor-alpha, and interleukin-1beta. Our results
      indicated that ZSCLE significantly and dose-dependently inhibited sepsis-induced
      liver and spleen injury. These results suggest that ZSCLE could provide a
      therapeutic agent for sepsis by inducing anti-inflammatory and anti-oxidant
      effects.

PMID- 29327285
TI  - Bernardino Ramazzini (1633-1714).

PMID- 29327284
TI  - Treatment of multiple sclerosis relapses with high-dose methylprednisolone
      reduces the evolution of contrast-enhancing lesions into persistent black holes.
AB  - INTRODUCTION: The MRI evidence of persistent black holes (pBHs) on T1-weighted
      images reflects brain tissue loss in multiple sclerosis (MS). The evolution of
      contrast-enhancing lesions (CELs) into pBHs probably depends on the degree and
      persistence of focal brain inflammation. The aim of our retrospective study was
      to evaluate the effect of a single cycle of intravenous methylprednisolone
      (IVMP), as for MS relapse treatment, on the risk of CELs' evolution into pBHs.
      PATIENTS AND METHODS: We selected 57 patients with CELs on the baseline MRI scan.
      We evaluated the evolution of CELs into pBHs on a follow-up MRI scan performed
      after >= 6 months in patients exposed and not exposed to IVMP for the treatment
      of relapse after the baseline MRI. RESULTS: In our cohort, 182 CELs were
      identified in the baseline MRI and 57 of them (31.3%) evolved into pBHs. In the
      multivariate analysis, the exposure of CELs to IVMP resulted to be a significant
      independent protective factor against pBHs' formation (OR 0.28, 95% CI 0.11
      0.766, p = 0.005), while ring enhancement pattern and the fact of being
      symptomatic were significant risk factors for CELs' conversion into pBHs (OR
      6.42, 95% CI 2.55-17.27, p < 0.001 and OR 13.19, 95% CI 1.56-288.87, p = 0.037).
      CONCLUSIONS: The exposure of CELs to a cycle of IVMP as for relapse treatment is
      associated with a lower risk of CELs' evolution into pBHs. Future studies are
      required to confirm the potential independent protective effect of IVMP on CELs'
      evolution into pBHs.

PMID- 29327287
TI  - Study of Effect of Impacting Direction on Abrasive Nanometric Cutting Process
      with Molecular Dynamics.
AB  - Abrasive flow polishing plays an important part in modern ultra-precision
      machining. Ultrafine particles suspended in the medium of abrasive flow removes
      the material in nanoscale. In this paper, three-dimensional molecular dynamics
      (MD) simulations are performed to investigate the effect of impacting direction
      on abrasive cutting process during abrasive flow polishing. The molecular
      dynamics simulation software Lammps was used to simulate the cutting of single
      crystal copper with SiC abrasive grains at different cutting angles (0o-45o). At
      a constant friction coefficient, we found a direct relation between cutting angle
      and cutting force, which ultimately increases the number of dislocation during
      abrasive flow machining. Our theoretical study reveal that a small cutting angle
      is beneficial for improving surface quality and reducing internal defects in the
      workpiece. However, there is no obvious relationship between cutting angle and
      friction coefficient.

PMID- 29327286
TI  - ABCD3-I score and the risk of early or 3-month stroke recurrence in tissue- and
      time-based definitions of TIA and minor stroke.
AB  - Changing definition of TIA from time to a tissue basis questions the validity of
      the well-established ABCD3-I risk score for recurrent ischemic cerebrovascular
      events. We analyzed patients with ischemic stroke with mild neurological symptoms
      arriving < 24 h after symptom onset in a phase where it is unclear, if the event
      turns out to be a TIA or minor stroke, in the prospective multi-center Austrian
      Stroke Unit Registry. Patients were retrospectively categorized according to a
      time-based (symptom duration below/above 24 h) and tissue-based (without/with
      corresponding brain lesion on CT or MRI) definition of TIA or minor stroke.
      Outcome parameters were early stroke during stroke unit stay and 3-month ischemic
      stroke. Of the 5237 TIA and minor stroke patients with prospectively documented
      ABCD3-I score, 2755 (52.6%) had a TIA by the time-based and 2183 (41.7%) by the
      tissue-based definition. Of the 2457 (46.9%) patients with complete 3-month
      followup, corresponding numbers were 1195 (48.3%) for the time- and 971 (39.5%)
      for the tissue-based definition of TIA. Early and 3-month ischemic stroke
      occurred in 1.1 and 2.5% of time-based TIA, 3.8 and 5.9% of time-based minor
      stroke, 1.2 and 2.3% of tissue-based TIA as well as in 3.1 and 5.5% of tissue
      based minor stroke patients. Irrespective of the definition of TIA and minor
      stroke, the risk of early and 3-month ischemic stroke steadily increased with
      increasing ABCD3-I score points. The ABCD3-I score performs equally in TIA
      patients in tissue- as well as time-based definition and the same is true for
      minor stroke patients.

PMID- 29327288
TI  - Expression of PFKFB3 and Ki67 in lung adenocarcinomas and targeting PFKFB3 as a
      therapeutic strategy.
AB  - Phosphofructokinase-2/fructose-2, 6-bisphosphatase 3 (PFKFB3) catalyzes the
      synthesis of F2,6BP, which is an allosteric activator of 6-phosphofructo-1-kinase
      (PFK-1): the rate-limiting enzyme of glycolysis. During tumorigenesis, PFKFB3
      increases glycolysis, angiogenesis, and tumor progression. In this study, our aim
      was to investigate the significance of PFKFB3 and Ki67 in human lung
      adenocarcinomas and to target PFKFB3 as a therapeutic strategy. In this study, we
      determined the expression levels of PFKFB3 mRNA and proteins in cancerous and
      normal lung adenocarcinomas by quantitative reverse transcription PCR (qRT-PCR),
      Western blot analysis, and tissue microarray immunohistochemistry analysis,
      respectively. In human adenocarcinoma tissues, PFKFB3 and Ki67 protein levels
      were related to the clinical characteristics and overall survival. Both PFKFB3
      mRNA and protein were significantly higher in lung adenocarcinoma cells (all P <
      0.05). A high expression of PFKFB3 and Ki67 were associated with the degree of
      differentiation, TNM staging, lymph node metastasis, and survival. A high
      expression of PFKFB3 protein was an independent prognostic marker in lung
      adenocarcinoma. Subsequently, 1-(4-pyridinyl)-3-(2-quinolinyl)-2-propen-1-one
      (PFK15) was used as a selective antagonist of PFKFB3. Glycolytic flux was
      determined by measuring glucose uptake, F2,6BP, and lactate production. Cell
      viability, cell cycle, cell apoptosis, cell migration, and invasion were analyzed
      by MTT, flow cytometry, Western blot analysis, wound healing assay, and transwell
      chamber assay. By targeting PFKFB3, it inhibited cell viability and glycolytic
      activity. It also caused apoptosis and induced cell cycle arrest. Furthermore,
      the migration and invasion of A549 cells was inhibited. We conclude that PFKFB3
      bears an oncogene-like regulatory element in lung adenocarcinoma progression. In
      the treatment of lung adenocarcinoma, targeting PFKFB3 would be a promising
      therapeutic strategy.

PMID- 29327289
TI  - Study of adenylyl cyclase-GalphaS interactions and identification of novel AC
      ligands.
AB  - Adenylyl cyclases (ACs) are membrane bound enzymes that catalyze the production
      of cAMP from ATP in response to the activation by G-protein Galphas. Different
      isoforms of ACs are ubiquitously expressed in different tissues involved in
      regulatory mechanisms in response to specific stimulants. There are 9 AC isoforms
      present in humans, with AC5 and AC6 proposed to play a vital role in cardiac
      functions. The activity of AC6 is sensitive to nitric oxide, such that
      nitrosylation of the protein might regulate its function. However, the
      information on structural determinants of nitrosylation in ACs and how they
      interact with Galphas is limited. Here we used homology modeling to build a
      molecular model of human AC6 bound to Galphas. Based on this 3D model, we predict
      the nitrosylation amenable cysteines, and identify potential novel ligands of AC6
      using virtual ligand screening. Our model suggests Cys1004 in AC6 (subunit C2)
      and Cys174 in Galphas present at the AC-Galphas interface as the possible
      residues that might undergo reversible nitrosylation. Docking analysis predicted
      novel ligands of AC6 that include forskolin-based compounds and its derivatives.
      Further work involving site-directed mutagenesis of the predicted residues will
      allow manipulation of AC activity using novel ligands, and crucial insights on
      the role of nitrosylation of these proteins in pathophysiological conditions.

PMID- 29327291
TI  - Pars plana vitrectomy with transscleral fixation of posterior chamber lens in the
      treatment of post-traumatic lens dislocation.
AB  - PURPOSE: To present our experience with post-traumatic lens dislocation
      management by vitrectomy followed with sutureless artificial lens fixation.
      METHODS: The retrospective study involved 15 patients (12 men and 3 women) aged
      from 36 to 78 (on average, 63 years old), from the Vitreoretinal Surgery Teaching
      Hospital, operated in the years 2013-2015. All cases concerned ocular traumas
      with dislocation of the natural or artificial lens to the anterior chamber,
      vitreous body chamber, or post-traumatic aphakia. After vitrectomy, patients had
      the implant fixated with a technique devised by Scharioth-sutureless fixation of
      posterior chamber implants in the groove area, with haptics placed in scleral
      tunnels parallel to the corneal limbus. Preoperative and postoperative condition
      of the eye was assessed. RESULTS: The average period of observation was 29 weeks.
      Average pre-surgery refraction was + 10.75, while post-surgery + 1.25. Average
      best-corrected visual acuity in Snellen charts before surgery was 0.3 and at the
      end of the observation period 0.5. The improvement in visual acuity after surgery
      in relation to visual acuity before surgery was statistically significant (P =
      0.005). In the first 2 weeks after surgery, minor hypotonia was observed in three
      of the patients, while in two-moderate bleeding to the vitreous body and the
      anterior chamber, which subsided without surgical intervention. A slight
      decentration of the implant observed in two cases did not affect later refraction
      or BCVA. CONCLUSION: Basing on the abovementioned facts, we believe that this
      surgical approach facilitates the fixation of the dislocated lens and allows a
      successful treatment of secondary implantation or repositioning of a dislocated
      intraocular lens.

PMID- 29327290
TI  - The diagnostic performance of reduced-dose CT for suspected appendicitis in
      paediatric and adult patients: A systematic review and diagnostic meta-analysis.
AB  - OBJECTIVE: To evaluate the diagnostic performance of reduced-dose CT for
      suspected appendicitis. METHODS: A systematic search of the MEDLINE and EMBASE
      databases was carried out through to 10 January 2017. Studies evaluating the
      diagnostic performance of reduced-dose CT for suspected appendicitis in
      paediatric and adult patients were selected. Pooled summary estimates of
      sensitivity and specificity were calculated using hierarchical logistic
      regression modelling. Meta-regression was performed. RESULTS: Fourteen original
      articles with a total of 3,262 patients were included. For all studies using
      reduced-dose CT, the summary sensitivity was 96 % (95 % CI 93-98) with a summary
      specificity of 94 % (95 % CI 92-95). For the 11 studies providing a head-to-head
      comparison between reduced-dose CT and standard-dose CT, reduced-dose CT
      demonstrated a comparable summary sensitivity of 96 % (95 % CI 91-98) and
      specificity of 94 % (95 % CI 93-96) without any significant differences (p=.41).
      In meta-regression, there were no significant factors affecting the
      heterogeneity. The median effective radiation dose of the reduced-dose CT was 1.8
      mSv (1.46-4.16 mSv), which was a 78 % reduction in effective radiation dose
      compared to the standard-dose CT. CONCLUSION: Reduced-dose CT shows excellent
      diagnostic performance for suspected appendicitis. KEY POINTS: * Reduced-dose CT
      shows excellent diagnostic performance for evaluating suspected appendicitis. *
      Reduced-dose CT has a comparable diagnostic performance to standard-dose CT. *
      Median effective radiation dose of reduced-dose CT was 1.8 mSv (1.46-4.16). *
      Reduced-dose CT achieved a 78 % dose reduction compared to standard-dose CT.

PMID- 29327293
TI  - Overexpression of spoT gene in coccoid forms of clinical Helicobacter pylori
      isolates.
AB  - Helicobacter pylori (H. pylori) can convert to coccoid form in unfavorable
      conditions or as a result of antibiotic treatment. In order to adapt to harsh
      environments, H. pylori requires a stringent response which, encoded by the spoT
      gene, has a bifunctional enzyme possessing both (p)ppGpp synthetic and degrading
      activity. Our goal in this study was to compare spoT gene expression in spiral
      and induced coccoid forms of H. pylori with use of amoxicillin. First, clinical
      isolate coccoid forms were induced with amoxicillin; then, the viability test was
      analyzed by flow cytometer. After RNA extraction, cDNA synthesis and designing a
      specific primer for spoT gene, evaluation of the desired gene expression in both
      forms were studied. Bacterial isolates exposed to amoxicillin at MIC and 1/2 MIC
      induced morphological conversion better and faster than other MIC concentration.
      The expression of spoT gene was significantly downregulated in spiral forms of H.
      pylori, while the gene expression was upregulated and + 30.3-fold changes was
      seen in coccoid forms of bacterium. To summarize, spoT gene is one of the key
      factors for antibiotic resistance and its enhanced expression in coccoid form can
      be a valuable diagnostic marker for recognition of H. pylori during morphological
      conversion.

PMID- 29327292
TI  - Alterations of growth rate and gene expression levels of UPEC by antibiotics at
      sub-MIC.
AB  - The host is the main environment for bacteria, and they also expose to many
      antibiotics during the treatment of infectious diseases in host body. In this
      study, it was aimed to investigate possible changes in growth rate and expression
      levels of three virulence genes (foc/foc, cnf1, and usp) in a uropathogenic E.
      coli standard strain within the presence of ciprofloxacin, nitrofurantoin, and
      trimethoprim-sulfamethoxazole. The UPEC C7 strain was grown on tryptic soy broth
      TSB (control), TSB + ciprofloxacin, TSB + nitrofurantoin, and TSB + trimethoprim
      sulfamethoxazole for determination of both growth rate and gene expression level.
      Antibiotics were added according to their sub-minimal inhibition concentrations.
      E-test was used to determine MIC values of antibiotics. Growth changes were
      measured in absorbance 600 nm during 24-h period. Total RNA isolations were
      performed after incubation for 24 h at 37  degrees C. Gene expression levels were
      determined by quantitative PCR. Tukey's post hoc test was used for statistical
      analysis. According to absorbance values, it has been shown that only
      ciprofloxacin and trimethoprim-sulfamethoxazole have lead significant decrease on
      growth rate. We also detected statistically significant differences in each gene
      expression levels for all antibiotics via relative quantification analysis. Fold
      changes in gene expression was found 0.65, 1.42, 0.23 for foc/foc gene; 0.01,
      0.01, 2.84 for cnf1 gene; and 0.1, 0.01, 0.01 for usp gene in the presence of
      ciprofloxacin, nitrofurantoin, and trimethoprim/sulfamethoxazole, respectively.
      This investigation has shown that antibiotics can play a role as an environmental
      factor which may determine the pathogenicity of bacteria in vivo.

PMID- 29327295
TI  - Common Deficiencies of in vitro Binding Bioequivalence (BE) Studies Submitted in
      Abbreviated New Drug Applications (ANDAs).
AB  - There are several drug products that bind phosphate or bile acid in the
      gastrointestinal (GI) tract to exert their therapeutic efficacy. In vitro binding
      studies are used to assess bioequivalence (BE) of these products. The objective
      of this study is to identify the common deficiencies in Abbreviated New Drug
      Applications (ANDAs) for these products. Deficiencies were compiled from ANDAs
      containing in vitro binding BE studies. The deficiencies were classified into
      eight categories: Pre-Study Method Validation, During-Study Sample Analysis,
      Study Design, Study Procedure, Dissolution/Disintegration, Analytical Site
      Inspection, Data Submission, and Formulations. Within each category, additional
      subcategories were defined to characterize the deficiencies. A total of 712
      deficiencies from 95 ANDAs for 11 drug products were identified and included in
      the analysis. The four categories with the most deficiencies were During-Study
      Sample Analysis (27.8%), Pre-Study Method Validation (17.3%), Data Submission
      (16.7%), and Study Design (15.7%). For the During-Study Sample Analysis category,
      failure to submit complete raw data or analytical runs ranked as the top
      deficiency (32.8%). For the Study Design category, using an unacceptable
      alternate study design (26.8%) was the most common deficiency. Within this
      category, other commonly occurring deficiencies included incorrect/insufficient
      number of absorbent concentrations, failure to pre-treat drug product with acid,
      insufficient number of replicates in study, incorrect calculation of k1 and k2
      values, incorrect dosage form or pooled samples used in the study, and incorrect
      pH of study medium. The review and approval of these products may be accelerated
      if these common deficiencies are addressed in the original ANDA submissions.

PMID- 29327294
TI  - Low risk for hip fracture and high risk for hip arthroplasty due to
      osteoarthritis among Swedish farmers.
AB  - : We aimed to study the risk of hip fracture and risk of hip arthroplasty among
      farmers in Sweden. Our results indicate that farming, representing an occupation
      with high physical activity, in men is associated with a lower risk of hip
      fracture but an increased risk of hip arthroplasty. INTRODUCTION: The risks of
      hip fracture and hip arthroplasty are influenced by factors including
      socioeconomic status, education, urbanization, latitude of residence, and
      physical activity. Farming is an occupation encompassing rural living and high
      level of physical activity. Therefore, we aimed to study the risk of hip fracture
      and risk of hip arthroplasty among farmers in Sweden. METHODS: We studied the
      risk of hip fracture, and hip arthroplasty due to primary osteoarthritis, in all
      men and women aged 35 years or more in Sweden between 1987 and 2002. Documented
      occupations were available in 3.5 million individuals, of whom 97,136 were
      farmers. The effects of age, sex, income, education, location of residence, and
      occupation on risk of hip fracture or hip arthroplasty were examined using a
      modification of Poisson regression. RESULTS: A total of 4027 farmers and 93,109
      individuals with other occupations sustained a hip fracture, while 5349 farmers
      and 63,473 others underwent a hip arthroplasty. Risk of hip fracture was higher
      with greater age, lower income, lower education, higher latitude, and urban area
      for all men and women. Compared to all other occupations, male farmers had a 20%
      lower age-adjusted risk of hip fracture (hazard ratio (HR) 0.80, 95%CI 0.77
      0.84), an effect that was not seen in female farmers (HR 0.96, 95% CI 0.91-1.01).
      Both male and female farmers had a higher age-adjusted risk for hip arthroplasty.
      CONCLUSIONS: Our results indicate that farming, representing an occupation with
      high physical activity, in men is associated with a lower risk of hip fracture
      but an increased risk of hip arthroplasty.

PMID- 29327296
TI  - Correction to: Dietary intake of soy and cruciferous vegetables and treatment
      related symptoms in Chinese-American and non-Hispanic White breast cancer
      survivors.
AB  - In the original publication, the values provided for the isoflavone and
      glucosinolate intake variables were incorrectly labeled in Table 1. The correct
      values of 6.3 mg/day for isoflavone intake, and 20.4 mg/day and 50.1 mg/day for
      glucosinolate intake are provided in this erratum.

PMID- 29327297
TI  - Correction to: Breast-conserving surgery following neoadjuvant therapy-a
      systematic review on surgical outcomes.
AB  - In the original publication of the article, Table 2 was published incorrectly.
      The corrected Table 2 is given in this erratum. The original article has been
      corrected.

PMID- 29327298
TI  - The impact of obesity on outcomes for patients undergoing mastectomy using the
      ACS-NSQIP data set.
AB  - PURPOSE: According to the World Health Organization (WHO), 34.7% of females in
      the United States are obese (BMI >= 30) in 2014, compared to 32.5% in 2010. The
      previous research has demonstrated high BMI as an independent risk factor for
      surgical complications after breast surgery. As more patients become obese, we
      sought to examine whether increasing obesity had an effect on outcomes of women
      who underwent a unilateral mastectomy without breast reconstruction. METHODS: The
      study reviewed the 2007-2012 ACS-NSQIP database and identified all patients who
      underwent a unilateral mastectomy without reconstruction. Patients were then
      categorized and compared according to the World Health Organization obesity
      classification. Data were analyzed for minor complications (e.g., UTI and SSI)
      and major complications (e.g., renal failure, sepsis, deep vein thrombosis,
      return to operating room [RTOR], and cardiac arrest). RESULTS: A total of 7207
      women were identified. Median BMI was 27.3 kg/m2. From the cohort, 453 patients
      (6.29%) had a major complication and 173 patients (2.40%) had a minor
      complication. 53 (0.74%) had bleeding complications, 148 (2.05%) had a surgical
      site infection (SSI), 352 (4.88%) RTOR, and 7 (0.01%) died within 30 days. Major
      complications (p = 0.005) and minor complications (p < 0.001) significantly
      increased as BMI increased. SSI and RTOR had increasing trends, but were not
      statistically significant. CONCLUSIONS: This study characterizes the risk of
      complications in women undergoing unilateral mastectomies and shows that
      increasing obesity is associated with major and minor postoperative
      complications. Our finding highlights the need for personalized preoperative risk
      assessment and counseling of obese patients.

PMID- 29327299
TI  - Impact of subclinical hypothyroidism with TSH <=10 mIU/L on glomerular filtration
      rate in adult women without known kidney disease.

PMID- 29327300
TI  - Cantu syndrome with coexisting familial pituitary adenoma.
AB  - CONTEXT: Pseudoacromegaly describes conditions with an acromegaly related
      physical appearance without abnormalities in the growth hormone (GH) axis.
      Acromegaloid facies, together with hypertrichosis, are typical manifestations of
      Cantu syndrome. CASE DESCRIPTION: We present a three-generation family with 5
      affected members, with marked acromegaloid facies and prominent hypertrichosis,
      due to a novel missense variant in the ABCC9 gene. The proband, a 2-year-old
      girl, was referred due to marked hypertrichosis, noticed soon after birth,
      associated with coarsening of her facial appearance. Her endocrine assessment,
      including of the GH axis, was normal. The proband's father, paternal aunt, and
      half-sibling were referred to the Endocrine department for exclusion of
      acromegaly. Although the GH axis was normal in all, two subjects had clinically
      non-functioning pituitary macroadenomas, a feature which has not previously been
      associated with Cantu syndrome. CONCLUSIONS: Activating mutations in the ABCC9
      and, less commonly, KCNJ8 genes-representing the two subunits of the ATP
      sensitive potassium channel-have been linked with Cantu syndrome. Interestingly,
      minoxidil, a well-known ATP-sensitive potassium channel agonist, can cause a
      similar phenotype. There is no clear explanation why activating this channel
      would lead to acromegaloid features or hypertrichosis. This report raises
      awareness for this complex condition, especially for adult or pediatric
      endocrinologists who might see these patients referred for evaluation of
      acromegaloid features or hirsutism. The link between Cantu syndrome and pituitary
      adenomas is currently unclear.

PMID- 29327302
TI  - Diffuse idiopathic skeletal hyperostosis is associated with lumbar spinal
      stenosis requiring surgery.
AB  - Factors related to the onset and progression of lumbar spinal stenosis (LSS) have
      not yet been identified. Diffuse idiopathic skeletal hyperostosis (DISH)
      increases mechanical loading on the non-fused lumbar levels and may therefore
      lead to LSS. This cross-sectional study aimed to identify associations between
      LSS and DISH. This study included 2363 consecutive patients undergoing surgery
      for LSS and 787 general inhabitants without symptoms of LSS as participants of
      the population-based cohort study, Research on Osteoarthritis/Osteoporosis
      Against Disability. Standing whole-spine radiographs were used to diagnose DISH
      based on the criteria proposed by Resnick and Niwayama. The prevalence of DISH
      showed a significant step-wise increase among asymptomatic inhabitants without
      radiographic LSS, asymptomatic inhabitants with radiographic LSS, and patients
      with LSS requiring surgery (14.4, 21.1, and 31.7%, respectively; p < 0.001). The
      distribution of DISH was similar between the groups, but the lower thoracic and
      upper-middle lumbar spine regions were more frequently involved in patients with
      LSS requiring surgery. Multivariate analysis indicated that DISH was an
      independent associated factor for LSS requiring surgery (adjusted odds ratio
      1.65; 95% confidence interval 1.32-2.07) after adjustment for age, sex, body mass
      index, and diabetes mellitus. Among patients with LSS requiring surgery, a higher
      occurrence of stenosis at the upper lumbar levels and multi-level stenosis were
      observed in patients with DISH requiring surgery than in patients without DISH.
      In conclusion, DISH is independently associated with LSS requiring surgery. The
      decrease in the lower mobile segments by DISH may increase the onset or severity
      of LSS.

PMID- 29327303
TI  - Differential osteopontin expression in human osteoblasts derived from iliac crest
      and alveolar bone and its role in early stages of angiogenesis.
AB  - In our previous study, we revealed significant differences of osteopontin (OPN)
      gene expression in primary human osteoblasts (HOBs) derived from iliac crest bone
      (iHOBs) and alveolar bone (aHOBs). The present study aims at assigning this
      discriminative expression to a possible biologic function. OPN is known to be
      involved in several pathologic and physiologic processes, among others
      angiogenesis. Therefore, we studied the reaction of human umbilical vein
      endothelial cells (HUVECs) to HOB-derived OPN regarding angiogenesis. To this
      end, human primary explant cultures of both bone entities from ten donors were
      established. Subsequent transcription analysis detected higher gene expression of
      OPN in iHOBs compared to aHOBs, thereby confirming the results of our previous
      study. This difference was particularly apparent when cultures were derived from
      female donors. Hence, OPN protein expression as well as the angiogenic potential
      of OPN was analyzed, originating from HOBs of one female donor. In accordance to
      the gene expression level, secreted OPN was more abundant in the supernatant of
      iHOBs than in aHOBs. Moreover, secreted OPN was found to stimulate migration of
      HUVECs, but not proliferation or tube formation. These results indicate an
      involvement in very early stages of angiogenesis and a functional distinction of
      OPN from HOBs derived from different bone entities.

PMID- 29327304
TI  - The Irrigation Effect: How River Regulation Can Promote Some Riparian Vegetation.
AB  - River regulation impacts riparian ecosystems by altering the hydrogeomorphic
      conditions that support streamside vegetation. Obligate riparian plants are often
      negatively impacted since they are ecological specialists with particular
      instream flow requirements. Conversely, facultative riparian plants are
      generalists and may be less vulnerable to river regulation, and could benefit
      from augmented flows that reduce drought stress during hot and dry periods. To
      consider this 'irrigation effect' we studied the facultative shrub, netleaf
      hackberry (Celtis reticulata), the predominant riparian plant along the Hells
      Canyon corridor of the Snake River, Idaho, USA, where dams produce hydropeaking,
      diurnal flow variation. Inventories of 235 cross-sectional transects revealed
      that hackberry was uncommon upstream from the reservoirs, sparse along the
      reservoir with seasonal draw-down and common along two reservoirs with stabilized
      water levels. Along the Snake River downstream, hackberry occurred in fairly
      continuous, dense bands along the high water line. In contrast, hackberry was
      sparsely scattered along the free-flowing Salmon River, where sandbar willow
      (Salix exigua), an obligate riparian shrub, was abundant. Below the confluence of
      the Snake and Salmon rivers, the abundance and distribution of hackberry were
      intermediate between the two upstream reaches. Thus, river regulation apparently
      benefited hackberry along the Snake River through Hells Canyon, probably due to
      diurnal pulsing that wets the riparian margin. We predict similar benefits for
      some other facultative riparian plants along other regulated rivers with
      hydropeaking during warm and dry intervals. To analyze the ecological impacts of
      hydropeaking we recommend assessing daily maxima, as well as daily mean river
      flows.

PMID- 29327301
TI  - LncRNA GAS8-AS1 inhibits cell proliferation through ATG5-mediated autophagy in
      papillary thyroid cancer.
AB  - PURPOSE: The long non-coding RNA GAS8 antisense RNA 1 (lncRNA GAS8-AS1) is a
      tumor suppressor in papillary thyroid cancer (PTC), but the mechanisms underlying
      how GAS8-AS1 regulates PTC biology remain unclear. Here, we evaluated the
      molecular function of GAS8-AS1 in regulating autophagy in PTC cell lines.
      METHODS: GAS8-AS1 was overexpressed and knocked down in PTC cell lines by
      transfecting with expression plasmids or short interfering RNAs (siRNAs). Cell
      proliferation was evaluated using the Cell Counting Kit-8 (CCK-8). qRT-PCR and
      western blot were used to determine changes in expression of autophagy-related
      genes. Autophagy was evaluated by immunofluorescence and transmission electron
      microscopy. RESULTS: Relative GAS8-AS1 expression was lower in the PTC cell
      lines, TPC1 and BCPAP, compared to a normal thyroid cell line. Overexpression of
      GAS8-AS1 inhibited proliferation, significantly increased the ratio of LC3-II/LC3
      I, and reduced p62 expression, whereas GAS8-AS1 knockdown demonstrated opposite
      effects. In GAS8-AS1 overexpressing cell lines, LC3 immunofluorescence staining
      demonstrated increased punctate aggregates of LC3 staining, and transmission
      electron microscopy revealed increased numbers of autophagosomes. Autophagy
      related gene 5 (ATG5) was markedly upregulated by GAS8-AS1 overexpression and
      downregulated by GAS8-AS1 knockdown. Finally, silencing of ATG5 attenuated
      autophagy activation and rescued the inhibition of cell proliferation caused by
      GAS8-AS1. CONCLUSIONS: In PTC cell lines, GAS8-AS1 inhibited proliferation,
      activated autophagy, and increased ATG5 expression. Downregulation of ATG5
      reversed GAS8-AS1-mediated activation of autophagy leading to cell death,
      revealing a novel mechanism of the GAS8-AS1-ATG5 axis in PTC cell lines. This
      provided a new experimental basis to explore the effects of lncRNA on autophagy
      in the treatment of thyroid cancer.

PMID- 29327305
TI  - Five-year postoperative outcomes of modified staged canal wall up tympanoplasty
      for primary acquired cholesteatoma.
AB  - OBJECTIVE: For successful canal wall up tympanoplasty (CWUT) for the treatment of
      cholesteatoma, the restoration of stable middle ear aeration is also important;
      however, little is known about the dynamics of such aeration or the optimal
      surgical procedure. In this study, alternative additional surgical procedure was
      selected based on the grade of middle ear aeration during the second-stage
      operation. SUBJECTS AND METHODS: Patients included in this study underwent staged
      CWUT surgeries with mastoid cortex plasty (MCP) for well-aerated ears (grade 3)
      and bony mastoid obliteration (BMO) for poorly aerated ears (grade 2-0). Of the
      115 ears included in this study, 62 were followed for more than 5 years.
      Recurrence rates with deep retraction pocket formation were assessed using the
      Kaplan-Meier survival analysis. The aeration was graded as: 0, no aeration; 1,
      aeration of only the mesotympanum; 2, aeration of the entire tympanic cavity; and
      3, aeration of both the tympanic and mastoid cavities. RESULTS: No recurrence was
      observed in ears associated with grade 3 aeration that underwent MCP or in ears
      with grade 2 aeration that underwent BMO during second-stage surgery. For grades
      0 and 1 aeration ears, the recurrence rates were 8.1% after 5 years and 12.5%
      after 10 years (p < 0.05), and the aeration of recurrent ears deteriorated to
      grade 0. CONCLUSION: Aeration during second-stage surgery predicts the final
      outcome.

PMID- 29327306
TI  - Strengthening the case for gender-neutral and the nonavalent HPV vaccine.
AB  - PURPOSE: The purpose of this review is to highlight the benefits of gender
      neutral and the nonavalent human papillomavirus vaccination. Human papillomavirus
      infection is the most commonly sexually transmitted disease and is known to cause
      several types of cancers, including cervical, vulvar, vaginal, penile,
      oropharyngeal, anal, and rectal. 5% of cancers every year are attributable to
      human papillomavirus infection, with cervical cancer the most common and
      oropharyngeal cancer estimated to surpass the incidence of cervical cancer by
      2020. METHODS: PubMed and MEDLINE were searched using the following search terms:
      [(human papillomavirus OR HPV) AND (vaccine OR vaccination)] AND [(gardasil OR
      gardasil9 OR cervarix OR quadrivalent OR nonavalent OR ninevalent) OR (gender
      neutral OR male)]. RESULTS: There are currently three different types of human
      papillomavirus vaccinations and range in cover from four to nine different
      strains known to cause human disease. Most countries currently only supply
      vaccination to females; however, recent data point towards both a personal
      benefit as well as a cost-effective population-based benefit with gender-neutral
      vaccination. Data from female vaccination only have shown the vaccine to be
      effective in preventing premalignant cervical lesions, and are believed to have
      the same effect for other human papillomavirus cancers. Male vaccination not only
      provides personal benefit but also has a "herd effect" for females by preventing
      the propagation of the virus. CONCLUSION: Gender-neutral vaccination provides
      significant cost-effective benefits for preventing human papillomavirus-related
      diseases, and this effect is further enhanced by the use of the nonavalent
      vaccine.

PMID- 29327308
TI  - Methionine in Proteins: It's Not Just for Protein Initiation Anymore.
AB  - Methionine in proteins is often thought to be a generic hydrophobic residue,
      functionally replaceable with another hydrophobic residue such as valine or
      leucine. This is not the case, and the reason is that methionine contains sulfur
      that confers special properties on methionine. The sulfur can be oxidized,
      converting methionine to methionine sulfoxide, and ubiquitous methionine
      sulfoxide reductases can reduce the sulfoxide back to methionine. This redox
      cycle enables methionine residues to provide a catalytically efficient
      antioxidant defense by reacting with oxidizing species. The cycle also
      constitutes a reversible post-translational covalent modification analogous to
      phosphorylation. As with phosphorylation, enzymatically-mediated oxidation and
      reduction of specific methionine residues functions as a regulatory process in
      the cell. Methionine residues also form bonds with aromatic residues that
      contribute significantly to protein stability. Given these important functions,
      alteration of the methionine-methionine sulfoxide balance in proteins has been
      correlated with disease processes, including cardiovascular and neurodegenerative
      diseases. Methionine isn't just for protein initiation.

PMID- 29327307
TI  - Nucleoside-Lipid-Based Nanocarriers for Sorafenib Delivery.
AB  - Although the application of sorafenib, a small inhibitor of tyrosine protein
      kinases, to cancer treatments remains a worldwide option in chemotherapy, novel
      strategies are needed to address the low water solubility (< 5 MUM), toxicity,
      and side effects issues of this drug. In this context, the use of nanocarriers is
      currently investigated in order to overcome these drawbacks. In this
      contribution, we report a new type of sorafenib-based nanoparticles stabilized by
      hybrid nucleoside-lipids. The solid lipid nanoparticles (SLNs) showed negative or
      positive zeta potential values depending on the nucleoside-lipid charge.
      Transmission electron microscopy of sorafenib-loaded SLNs revealed parallelepiped
      nanoparticles of about 200 nm. Biological studies achieved on four different cell
      lines, including liver and breast cancers, revealed enhanced anticancer
      activities of Sorafenib-based SLNs compared to the free drug. Importantly,
      contrast phase microscopy images recorded after incubation of cancer cells in the
      presence of SLNs at high concentration in sorafenib (> 80 MUM) revealed a total
      cancer cell death in all cases. These results highlight the potential of
      nucleoside-lipid-based SLNs as drug delivery systems.

PMID- 29327309
TI  - Ischemia-Reperfusion Injury of Sciatic Nerve in Rats: Protective Role of
      Combination of Vitamin C with E and Tissue Plasminogen Activator.
AB  - An ischemia/reperfusion injury of rat's sciatic nerve was experimentally
      developed. In this model, we measured the in vivo production of superoxide
      radical, as a marker of oxidative stress and the occludin expression as an
      indicator of blood-nerve barrier function and we examined potential protective
      innervations against these abnormalities. Right sciatic nerves of the animals
      underwent 3 h of ischemia followed by 7 days of reperfusion and were divided into
      three groups: ischemic, pretreated with vitamin C in conjunction with vitamin E
      and treated with tissue plasminogen activator. Compared to measurements from left
      sciatic nerves used as sham, the ischemic group showed significantly increased
      superoxide radical and reduced expression of occludin in western blot and
      immunohistochemistry. No such differences were detected between sham and nerves
      in the vitamin or tissue plasminogen activator groups. It is suggested that the
      experimental ischemia/reperfusion model was suitable for studying the
      relationship between oxidative state and blood-nerve barrier. The reversion of
      abnormalities by the applied neuroprotective agents might prove to be a
      clinically important finding in view of the implication of vascular supply
      derangement in various neuropathies in humans.

PMID- 29327311
TI  - Sequentially Vapor-Grown Hybrid Perovskite for Planar Heterojunction Solar Cells.
AB  - High-quality and reproducible perovskite layer fabrication routes are essential
      for the implementation of efficient planar solar cells. Here, we introduce a
      sequential vapor-processing route based on physical vacuum evaporation of a PbCl2
      layer followed by chemical reaction with methyl-ammonium iodide vapor. The
      demonstrated vapor-grown perovskite layers show compact, pinhole-free, and
      uniform microstructure with the average grain size of ~ 320 nm. Planar
      heterojunction perovskite solar cells are fabricated using TiO2 and spiro-OMeTAD
      charge transporting layers in regular n-i-p form. The devices exhibit the best
      efficiency of 11.5% with small deviation indicating the high uniformity and
      reproducibility of the perovskite layers formed by this route.

PMID- 29327310
TI  - C-Reactive Protein on Postoperative Day 1 Is a Reliable Predictor of Pancreas
      Specific Complications After Pancreaticoduodenectomy.
AB  - BACKGROUND: Postoperative pancreatic fistula and pancreas-specific complications
      have a significant influence on patient management and outcomes after
      pancreatoduodenectomy. The aim of the study was to assess the value of serum C
      reactive protein on the postoperative day 1 as early predictor of pancreatic
      fistula and pancreas-specific complications. METHODS: Between 2013 and 2016, 110
      patients underwent pancreaticoduodenectomy. Clinical, biological, intraoperative,
      and pathological characteristics were prospectively recorded. Pancreatic fistula
      was graded according to the International Study Group on Pancreatic Fistula
      classification. A composite endpoint was defined as pancreas-specific
      complications including pancreatic fistula, intra-abdominal abscess,
      postoperative hemorrhage, and bile leak. The diagnostic accuracy of serum C
      reactive protein on postoperative day 1 in predicting adverse postoperative
      outcomes was assessed by ROC curve analysis. RESULTS: Six patients (5%) died and
      87 (79%) experienced postoperative complications (pancreatic-specific
      complications: n = 58 (53%); pancreatic fistula: n = 48 (44%)). A soft pancreatic
      gland texture, a main pancreatic duct diameter < 3 mm and serum C-reactive
      protein >= 100 mg/L on postoperative day 1 were independent predictors of
      pancreas-specific complications (p < 0.01) and pancreatic fistula (p < 0.01). ROC
      analysis showed that serum C-reactive protein >= 100 mg/L on postoperative day 1
      was a significant predictor of pancreatic fistula (AUC: 0.70; 95%CI: 0.60-0.79, p
      < 0.01) and pancreas-specific complications (AUC: 0.72; 95%CI: 0.62-0.82, p <
      0.01). ROC analysis showed that serum C-reactive protein >= 50 mg/L at discharge
      was a significant predictor of 90-day hospital readmission (AUC: 0.70; 95%CI:
      0.60-0.79, p < 0.01). CONCLUSIONS: C-reactive protein levels reliably predict
      risks of pancreatic fistula, pancreas-specific complications, and hospital
      readmission, and should be inserted in risk-stratified management algorithms
      after pancreaticoduodenectomy.

PMID- 29327312
TI  - Examining the Prospective Relationship between Pre-Disaster Respiratory Sinus
      Arrhythmia and Post-Disaster Posttraumatic Stress Disorder Symptoms in Children.
AB  - Previous studies have examined the concurrent relationship between posttraumatic
      stress disorder (PTSD) and a range of psychophysiological variables, including
      respiratory sinus arrhythmia (RSA). However, there is a lack of research
      examining the prospective development of trauma symptomatology, and the
      directionality of the association between RSA level and PTSD has yet to be
      determined. The current study is the first prospective study to examine whether
      RSA level and RSA reactivity are risk factors for PTSD symptoms in children.
      Assessments were conducted both prior to (Time 1) and following (Time 2) a
      natural disaster (i.e., Hurricane Katrina). Participants were 36 children who
      were 3-6 years-old during the Time 1 assessment. Structured diagnostic interviews
      were used to assess PTSD symptoms at both Time 1 and Time 2. RSA level during a
      neutral stimulus, RSA reactivity to emotional video stimuli (distress, joy, and
      trauma videos) and RSA reactivity to memory stimuli (remote happy memory, trauma
      memory, mother's recall of the trauma memory) were also collected at both time
      points. Time 1 RSA level during a neutral stimulus was a significant predictor of
      Time 2 PTSD symptoms (controlling for age, Time 1 PTSD symptoms, Time 2 neutral
      RSA level), such that lower RSA during a neutral condition was related to higher
      PTSD symptoms. Also, Time 1 RSA reactivity in response to memory (but not video)
      stimuli, in the form of relatively less vagal withdrawal, was a significant
      predictor of more Time 2 PTSD symptoms (controlling for age, Time 1 PTSD
      symptoms, Time 2 RSA reactivity). This unique prospective study provides evidence
      for level of RSA and RSA reactivity as pre-existing clinical markers of stress
      sensitivity that predict psychopathology following a trauma.

PMID- 29327313
TI  - Reduction of Pain Sensitivity after Somatosensory Therapy in Children with Autism
      Spectrum Disorders.
AB  - Children with autism spectrum disorders (ASD) often present with somatosensory
      dysfunction including an abnormal reactivity to tactile stimuli and altered pain
      perception. A therapy based on somatosensory stimuli has shown effectiveness in
      reducing pain sensitivity among adults with cerebral palsy. The present study
      aims at exploring the influence of somatosensory therapy on somatosensory
      parameters in children with ASD. Children with high-functioning ASD were randomly
      assigned to either the intervention (n = 29) or the control group (n = 30). The
      intervention group received a somatosensory therapy consisting of four types of
      exercises (touch, proprioception, vibration, stereognosis). Somatosensory
      function (pressure pain thresholds, tactile thresholds, stereognosis,
      proprioception) was assessed before and immediately after the therapy. Children
      in the intervention group showed a significant reduction of pain sensitivity and
      increase of tactile sensitivity after treatment, whereas children in the control
      group displayed increased pain sensitivity in the absence of changes of tactile
      sensitivity. No changes were observed for proprioception or stereognosis. The
      repetitive somatosensory stimulation therapy led to a decrease of pain
      sensitivity and an increase of tactile sensitivity. These findings may have
      important research and clinical implications, as promoting early tactile
      interventions in children with ASD may lead to a more adequate development of
      somatosensory processing and less somatosensory abnormalities upon adult life.

PMID- 29327315
TI  - Maternal bonding behavior, adult intimate relationship, and quality of life.
AB  - Continuity and discontinuity in the development of social relationships have been
      investigated by reviewing the course of social bonds and by analyzing the effects
      of a sound intimate relationship in adulthood in conjunction with recalled
      maternal bonding on the quality of life among students.A questionnaire-based
      study of 207 students was conducted. Perceptions of maternal bonding were
      designated as being representative of one of the two contrasting bonding types
      "optimal maternal bonding" and "affectionless maternal control" assessed by the
      Parental Bonding Instrument (PBI) and combined with perceptions of a sound
      intimate adult relationship measured by the Family Assessment Measure III Dyadic
      Relationships Scale (FAM-III-D). Quality of life and general health data were
      determined by using the World Health Organization Quality of Life (WHOQOL-BREF)
      instrument.Students who reported "optimal maternal bonding" had intimate
      relationships in adulthood that were of significantly higher quality than those
      who recalled "affectionless maternal control". Students who recalled "optimal
      maternal bonding" and described their intimate relationship as sound showed
      significantly higher scores in all domains of quality of life and indicated
      having better general health than those who reported "affectionless maternal
      control" and a sound intimate relationship.A sound intimate relationship in
      adulthood does not appear to compensate the impact of a recalled maternal bonding
      behavior in terms of affectionless control, on quality of life. Furthermore,
      results seem to support the hypothesis of continuity of the development of social
      relationships among psychologically well individuals based on the association
      between maternal bonding and later intimate relationships.

PMID- 29327316
TI  - [Diagnosis, differential diagnosis and therapy of substance use disorders in
      general hospital (general section)].
AB  - Substance use disorders are becoming an increasingly significant problem in
      general hospitals and hence play a key role in consultation- and liaison
      psychiatry. Diverse psychotropic effects of various substances mimic psychiatric
      disorders. An alcohol intoxication can present depressive or manic symptoms, a
      cannabis delirium can present as a psychosis while stimulants use can suggest the
      diagnosis of an anxiety disorder. Obtaining dual diagnoses by identifying
      substance-induced and non-substance-induced psychopathologies is clinically
      challenging.The aim of this article is to systematically describe the
      psychopathology, pathophysiology and therapeutic options of substance-use
      disorders particularly relevant for consultation and liaison psychiatry.

PMID- 29327314
TI  - Computational Modeling for Cardiac Resynchronization Therapy.
AB  - Cardiac resynchronization therapy (CRT) is an effective treatment for heart
      failure (HF) patients with an electrical substrate pathology causing ventricular
      dyssynchrony. However 40-50% of patients do not respond to treatment. Cardiac
      modeling of the electrophysiology, electromechanics, and hemodynamics of the
      heart has been used to study mechanisms behind HF pathology and CRT response.
      Recently, multi-scale dyssynchronous HF models have been used to study optimal
      device settings and optimal lead locations, investigate the underlying cardiac
      pathophysiology, as well as investigate emerging technologies proposed to treat
      cardiac dyssynchrony. However the breadth of patient and experimental data
      required to create and parameterize these models and the computational resources
      required currently limits the use of these models to small patient numbers. In
      the future, once these technical challenges are overcome, biophysically based
      models of the heart have the potential to become a clinical tool to aid in the
      diagnosis and treatment of HF.

PMID- 29327318
TI  - Evaluation of water quality and human risk assessment due to heavy metals in
      groundwater around Muledane area of Vhembe District, Limpopo Province, South
      Africa.
AB  - Groundwater is considered as good alternative to potable water because of its low
      turbidity and perceived low contamination. The study assessed the physio-chemical
      and heavy metals concentrations in eight randomly selected boreholes water at
      Muledane village in Limpopo Province of South Africa and the results were
      compared with South African National standard permissible limit. The impacts of
      heavy metals on human health was further determined by performing quantitative
      risk assessment through ingestion and dermal adsorption of heavy metals
      separately for adults and children in order to estimate the magnitude of heavy
      metals in the borehole samples. Parameters such as turbidity, nitrate, iron,
      manganese and chromium in some investigated boreholes did not comply with
      standard limits sets for domestic water use. Multivariate analyses using
      principal component analysis and hierarchical cluster analysis revealed natural
      and anthropogenic activities as sources of heavy metal contamination in the
      borehole water samples. The calculated non-carcinogenic effects using hazard
      quotient toxicity potential, cumulative hazard index and chronic daily intake of
      groundwater through ingestion and dermal adsorption pathways were less than a
      unity, which showed that consumption of the water could pose little or no
      significant health risk. However, maximum estimated values for an individual
      exceeded the risk limit of 10-6 and 10-4 with the highest estimated carcinogenic
      exposure risk (CRing) for Cr and Pb in the groundwater. This could pose potential
      health risk to both adults and children in the investigated area. Therefore,
      precaution needs to be taken to avoid potential CRing of people in Muledane area
      especially, children using the borehole water.

PMID- 29327317
TI  - Transcript levels of members of the SLC2 and SLC5 families of glucose transport
      proteins in eel swimbladder tissue: the influence of silvering and the influence
      of a nematode infection.
AB  - The rate of glucose metabolism has been shown to be correlated to glucose uptake
      in swimbladder gas gland cells. Therefore, it is assumed that in the European eel
      silvering, i.e., the preparation of the eel for the spawning migration to the
      Sargasso Sea, coincides with an enhanced capacity for glucose uptake. To test
      this hypothesis expression of all known glucose transport proteins has been
      assessed at the transcript level in yellow and in silver eels, and we also
      included Anguillicola crassus infected swimbladders. Glucose uptake by rete
      mirabile endothelial cells could be crucial for the countercurrent exchange
      capacity of the rete. Therefore, this tissue was also included in our analysis.
      The results revealed expression of ten different members of the slc2 family of
      glucose transporters, of four slc5 family members, and of kiaa1919 in gas gland
      tissue. Glucose transporters of the slc2 family were expressed at very high
      level, and slc2a1b made up about 80% of all slc2 family members, irrespective of
      the developmental state or the infection status of the eel. Overall, the slc5
      family contributed to only about 8% of all detected glucose transport transcripts
      in gas gland tissue, and the slc2 family to more than 85%. In rete capillaries,
      the contribution of sodium-dependent glucose transporters was significantly
      higher, leaving only 66% for the slc2 family of glucose transporters. Neither
      silvering nor the infection status had a significant effect on the expression of
      glucose transporters in swimbladder gas gland tissue, suggesting that glucose
      metabolism of eel gas gland cells may not be related to transcriptional changes
      of glucose transport proteins.

PMID- 29327319
TI  - Antidepressant-Related Black Thyroid.

PMID- 29327320
TI  - Phylogenetic Analysis and Biological Evaluation of Marine Endophytic Fungi
      Derived from Red Sea Sponge Hyrtios erectus.
AB  - Forty-four endophytic fungal isolates obtained from marine sponge, Hyrtios
      erectus, were evaluated and screened for their hydrolase activities. Most of the
      isolates were found to be prolific producers of hydrolytic enzymes. Only 11
      isolates exhibited maximum cellular contents of lipids, rhamnolipids, and protein
      in the fungal isolates under the isolation numbers MERVA5, MERVA22, MERVA25,
      MERVA29, MERVA32, MERVA34, MERV36, MERVA39, MERVA42, MERVA43, and MERVA44. These
      isolate extracts exhibit the highest reducing activities against carbohydrate
      metabolizing enzymes including alpha-amylase, alpha-glucosidase, beta
      glucosidase, beta-glucuronidase, and tyrosinase. Consequently, based on
      morphological and cultural criteria, as well as sequence information and
      phylogenetic analysis, these isolates could be identified and designated as
      Penicillium brevicombactum MERVA5, Arthrinium arundinis MERVA22, Diaporthe rudis
      MERVA25, Aspergillus versicolor MERVA29, Auxarthron alboluteum MERVA32,
      Dothiorella sarmentorum MERVA34, Lophiostoma sp. MERVA36, Fusarium oxysporum
      MERVA39, Penicillium chrysogenum MERVA42, Penicillium polonicum MERVA43, and
      Trichoderma harzianum MERVA44. The endophytic fungal species, D. rudis MERVA25,
      P. polonicum MERVA43, Lophiostoma sp. MERVA36, A. alboluteum MERVA32, T.
      harzianum MERVA44, F. oxysporum MERVA39, A. versicolor MERVA29, and P.
      chrysogenum MERVA42 extracts, showed significant hepatitis C virus (HCV)
      inhibition. Moreover, D. sarmentorum MERVA34, P. polonicum MERVA43, and T.
      harzianum MERVA44 extracts have the highest antitumor activity against human
      hepatocellular carcinoma cells (HepG2).

PMID- 29327321
TI  - Preliminary Psychometric Testing of the Postpartum Depression Predictors
      Inventory-Revised (PDPI-R) in Portuguese Women.
AB  - Introduction Postpartum depression (PPD) is a prevalent condition with a serious
      impact. The early identification of women at risk for developing PPD allows for
      primary prevention and the delivery of timely appropriate referrals. This study
      investigated the validity and reliability of the postnatal version of the
      Postpartum Depression Predictors Inventory-Revised (PDPI-R), an instrument widely
      studied internationally, in Portuguese women. Methods The sample consisted of 204
      women who participated in an online cross-sectional survey. Participants
      completed the European Portuguese versions of the PDPI-R, the Edinburgh Postnatal
      Depression Scale (EPDS), and the Postnatal Negative Thoughts Questionnaire at 1-2
      months postpartum. Additionally, ROC analyses were performed to conduct an
      exploratory analysis of the instruments' predictive validity. Results The
      prevalence rates of clinical postpartum depressive symptoms were 27.5 and 14.2%
      using the cut-off scores of 9 and 12, respectively, on the EPDS. The European
      Portuguese postnatal version of the PDPI-R demonstrated acceptable reliability
      and satisfactory construct and convergent validity. When using the EPDS > 9 cut
      off score, the exploratory analyses yielded a sensitivity of 76.8% and a
      specificity of 73.0% with a cut-off score of 5.5 [area under the curve = 0.816].
      Discussion These preliminary findings encourage the use of the postnatal version
      of the PDPI-R as a screening tool to identify Portuguese women at high risk for
      developing PPD. Subsequent assessments are needed to support the routine
      application of the PDPI-R both in research and for clinical purposes.

PMID- 29327322
TI  - Molecular characterization of avian malaria in the spotless starling (Sturnus
      unicolor).
AB  - We studied the prevalence and genetic diversity of malaria parasites in the
      poorly investigated spotless starling (Sturnus unicolor) breeding in central
      Spain, aiming to describe the phylogenetic relationships among them and with
      other haemosporidians infecting the genus Sturnus. A total of 180 nestlings and
      180 adult individuals from four different breeding seasons were screened for
      haemosporidian parasites using a nested PCR approach for the genera Plasmodium
      and Haemoproteus. Although the malaria prevalence ranged between years, the
      overall prevalence was 6.94%. Adults had a higher prevalence than chicks: 12.77
      vs. 1.11%, respectively. We molecularly characterized avian malaria isolated in
      peripheral blood samples taken from malaria-infected individuals. Sequence
      analyses revealed four unique Plasmodium lineages of avian malaria (STURUNI01,
      STURUNI02, SYAT05, SGS1) in our spotless starling population. The phylogenetic
      analysis showed a well-supported clade comprised by STURUNI01, STURUNI02, and
      SYAT05. The most common lineage (SYAT05) has been previously found in 26 other
      avian host species, including populations of spotless starling in Portugal.
      Because this sedentary species is widely distributed throughout the Iberian
      Peninsula, we suggest that the local transmission of these lineages might place
      migratory birds at infection risk.

PMID- 29327323
TI  - Inclusion complex and nanoclusters of cyclodextrin to increase the solubility and
      efficacy of albendazole.
AB  - Albendazole (ABZ), a benzimidazole widely used to control gastrointestinal
      parasites, is poorly soluble in water, resulting in variable and incomplete
      bioavailability. This has favored the appearance ABZ-resistant nematodes and,
      consequently, an increase in its clinical ineffectiveness. Among the
      pharmaceutical techniques developed to increase drug efficacy, cyclodextrins
      (CDs) and other polymers have been extensively used with water-insoluble
      pharmaceutical drugs to increase their solubility and availability. Our objective
      was to prepare ABZ formulations, including beta-cyclodextrin (betaCD) or
      hydroxypropyl-beta-cyclodextrin (HPbetaCD), associated or not to the water
      soluble polymer polyvinylpyrrolidone (PVP). These formulations had their
      solubility and anthelmintic effect both evaluated in vitro. Also, their
      anthelmintic efficacy was evaluated in lambs naturally infected with
      gastrointestinal nematodes (GIN) through the fecal egg count (FEC) reduction
      test. In vitro, the complex ABZ/HPbetaCD had higher solubility than ABZ/betaCD.
      The addition of PVP to the complexes increased solubility and dissolution rates
      more effectively for ABZ/HPbetaCD than for ABZ/betaCD. In vivo, 48 lambs
      naturally infected with GIN were divided into six experimental groups: control,
      ABZ, ABZ/betaCD, ABZ/betaCD-PVP, ABZ/HPbetaCD, and ABZ/HPbetaCD-PVP. Each treated
      animal received 10 mg/kg of body weight (based on the ABZ dose) for three
      consecutive days. After 10 days of the last administered dose, treatment efficacy
      was calculated. The efficacy values were as follows: ABZ (70.33%), ABZ/betaCD
      (85.33%), ABZ/betaCD-PVP (82.86%), ABZ/HPbetaCD (78.37%), and ABZ/HPbetaCD-PVP
      (43.79%). In vitro, ABZ/HPbetaCD and ABZ/HPbetaCD-PVP had high solubility and
      dissolution rates. In vivo, although the efficacies of ABZ/betaCD, ABZ/betaCD
      PVP, and ABZ/HPbetaCD increased slightly when compared to pure ABZ, this increase
      was not significant (P > 0.05).

PMID- 29327324
TI  - Divergent Cryptosporidium parvum subtype and Enterocytozoon bieneusi genotypes in
      dromedary camels in Algeria.
AB  - Little information is available on the occurrence of the zoonotic protists
      Cryptosporidium spp. and none on Enterocytozoon bieneusi in camels. This
      preliminary study was conducted to examine the identity of Cryptosporidium
      subtypes and E. bieneusi genotypes in dromedary camels in Algeria. A total of 39
      fecal specimens were collected from young camels. PCR-sequence analysis of the
      small subunit rRNA was used to detect and genotype Cryptosporidium spp.
      Cryptosporidium parvum present was further subtyped by sequence analysis of the
      60 kDa glycoprotein gene. PCR-sequence analysis of the ribosomal internal
      transcribed spacer gene was used to detect and genotype E. bieneusi. Altogether,
      two and eight of the specimens analyzed were positive for C. parvum and E.
      bieneusi, respectively. The former was identified as a new subtype that is
      genetically related to the C. hominis If subtype family, whereas the latter was
      identified as two related genotypes (Macaque1 and a novel genotype) in the newly
      assigned E. bieneusi genotype group 8. Although they are not known hosts for C.
      parvum and E. bieneusi, camels are apparently infected with genetically distinct
      variants of these pathogens.

PMID- 29327325
TI  - Circulating level of Th17 cells is associated with sensitivity to glucocorticoids
      in patients with immune thrombocytopenia.
AB  - Glucocorticoids are a widely recognized first-line therapy for immune
      thrombocytopenia (ITP). However, some patients are unresponsive to glucocorticoid
      therapy for reasons that remain unclear. Accumulating evidence suggests that CD4+
      T-cell abnormalities play a crucial role in the development of ITP. In the
      present study, we investigated peripheral blood CD4+ T cells, Th17-associated
      cytokines, and the mRNA expression level of Th17 transcription factor-RORgammat
      in patients with newly-diagnosed ITP before glucocorticoid therapy. The study
      involved 27 newly-diagnosed patients. Th17-cell levels in the peripheral blood of
      newly-diagnosed ITP patients were associated with responsiveness to
      glucocorticoid therapy. Newly-diagnosed ITP patients who were not sensitive to
      glucocorticoid treatment were found to have lower levels of Th17 cells.
      Quantifying Th17 cells may allow physicians to predict prognosis of
      glucocorticoid treatment and stratify therapy for those with ITP. This strategy
      may provide a new approach to the treatment of glucocorticoid-insensitive
      patients.

PMID- 29327326
TI  - IL-11 facilitates a novel connection between RA joint fibroblasts and endothelial
      cells.
AB  - IL-11 has been detected in inflamed joints; however, its role in the pathogenesis
      of arthritis is not yet clear. Studies were conducted to characterize the
      expression and functional significance of IL-11 and IL-11Ralpha in rheumatoid
      arthritis (RA). IL-11 levels were elevated in RA synovial fluid (SF) compared to
      osteoarthritis (OA) SF and plasma from RA, OA and normal individuals (NLs).
      Morphologic studies established that IL-11 was detected in lining fibroblasts and
      macrophages in addition to sublining endothelial cells and macrophages at higher
      levels in RA compared to NL synovial tissues. Since IL-11Ralpha was exclusively
      expressed in RA fibroblasts and endothelial cells, macrophages were not involved
      in IL-11 effector function. Ligation of IL-11 to IL-11Ralpha strongly provoked
      fibroblast infiltration into RA joint, while cell proliferation was unaffected by
      this process. Secretion of IL-8 and VEGF from IL-11 activated RA fibroblasts was
      responsible for the indirect effect of IL-11 on endothelial cell transmigration
      and tube formation. Moreover, IL-11 blockade impaired RA SF capacity to elicit
      endothelial cell transmigration and tube formation. We conclude that IL-11
      binding to endothelial IL-11Ralpha can directly induce RA angiogenesis. In
      addition, secretion of proangiogenic factors from migrating fibroblasts
      potentiated by IL-11 can indirectly contribute to RA neovascularization.

PMID- 29327329
TI  - microRNA-mediated R gene regulation: molecular scabbards for double-edged swords.
AB  - Plant resistance (R) proteins are immune receptors that recognize pathogen
      effectors and trigger rapid defense responses, namely effector-triggered
      immunity. R protein-mediated pathogen resistance is usually race specific. During
      plant-pathogen coevolution, plant genomes accumulated large numbers of R genes.
      Even though plant R genes provide important natural resources for breeding
      disease-resistant crops, their presence in the plant genome comes at a cost.
      Misregulation of R genes leads to developmental defects, such as stunted growth
      and reduced fertility. In the past decade, many microRNAs (miRNAs) have been
      identified to target various R genes in plant genomes. miRNAs reduce R gene
      levels under normal conditions and allow induction of R gene expression under
      various stresses. For these reasons, we consider R genes to be double-edged
      "swords" and miRNAs as molecular "scabbards". In the present review, we summarize
      the contributions and potential problems of these "swords" and discuss the
      features and production of the "scabbards", as well as the mechanisms used to
      pull the "sword" from the "scabbard" when needed.

PMID- 29327330
TI  - Microbiome analysis and -omics studies of microbial denitrification processes in
      wastewater treatment: recent advances.
AB  - Nitrogen pollution is an increasingly severe worldwide problem because of
      drainage of nitrogen-containing wastewater and intensive application of nitrogen
      containing fertilizers. Denitrification, a key process in nitrogen cycles, is
      commonly employed for nitrogen removal in engineered wastewater treatment
      systems. Biological denitrification is performed by denitrifying microbes
      (bacteria) that use nitrate as terminal electron acceptor. Better understanding
      the functions of diverse microbial populations in denitrification-based
      wastewater treatment systems, and the interactions of these populations with
      operating environments, is essential for improving both treatment performance and
      system stability. Recent advances in "meta-omics" (e. g., genomics,
      transcriptomics, proteomics, metabolomics), other molecular biology tools, and
      microbiome analysis have greatly enhanced such understanding. This minireview
      summarizes recent findings regarding microbial community structure and
      composition, key functional microbes and their physiology, functional genes
      involved in nitrogen cycle, and responses of microbes and their genes to changes
      of environmental factors or operating parameters, in denitrification processes in
      wastewater treatment systems. Of particular interest are heterotrophic
      denitrification systems (which require alternative organic carbon sources) and
      the autotrophic denitrification systems (which do not require an external carbon
      source). Integrated microbiome and -omics approaches have great future potential
      for determination of optimal environmental and biotechnological parameters, novel
      process development, and improvement of nitrogen removal efficiency and system
      stability.

PMID- 29327328
TI  - Genetic analysis of very obese children with autism spectrum disorder.
AB  - Autism spectrum disorder (ASD) is defined by the triad of deficits in social
      interactions, deficits in communication, and repetitive behaviors. Common co
      morbidities in syndromic forms of ASD include intellectual disability, seizures,
      and obesity. We asked whether very obese children with ASD had different
      behavioral, physical and genetic characteristics compared to children with ASD
      who were not obese. We found that very obese children with ASD had significantly
      poorer scores on standardized behavioral tests. Very obese boys with ASD had
      lower full scale IQ and increased impairments with respect to stereotypies,
      communication and social skills. Very obese girls with ASD had increased
      impairments with respect to irritability and oppositional defiant behavior. We
      identified genetic lesions in a subset of the children with ASD and obesity and
      attempted to identify enriched biological pathways. Our study demonstrates the
      value of identifying co-morbidities in children with ASD as we move forward
      towards understanding the biological processes that contribute to this complex
      disorder and prepare to design customized treatments that target the diverse
      genetic lesions present in individuals with ASD.

PMID- 29327331
TI  - Calibration of peripheral perception of shape with and without saccadic eye
      movements.
AB  - The cortical representations of a visual object differ radically across saccades.
      Several studies claim that the visual system adapts the peripheral percept to
      better match the subsequent foveal view. Recently, Herwig, Weibeta, and Schneider
      (2015, Annals of the New York Academy of Sciences, 1339(1), 97-105) found that
      the perception of shape demonstrates a saccade-dependent learning effect. Here,
      we ask whether this learning actually requires saccades. We replicated Herwig et
      al.'s (2015) study and introduced a fixation condition. In a learning phase,
      participants were exposed to objects whose shape systematically changed during a
      saccade, or during a displacement from peripheral to foveal vision (without a
      saccade). In a subsequent test, objects were perceived as less (more) curved if
      they previously changed from more circular (triangular) in the periphery to more
      triangular (circular) in the fovea. Importantly, this pattern was seen both with
      and without saccades. We then tested whether a variable delay between the
      presentations of the peripheral and foveal objects would affect their association
      hypothetically weakening it at longer delays. Again, we found that shape
      judgments depended on the changes experienced during the learning phase and that
      they were similar in both the saccade and fixation conditions. Surprisingly, they
      were not affected by the delay between the peripheral and foveal presentations
      over the range we tested. These results suggest that a general associative
      process, independent of saccade execution, contributes to the perception of shape
      across viewpoints.

PMID- 29327327
TI  - Identifying potentially common genes between dyslipidemia and osteoporosis using
      novel analytical approaches.
AB  - Dyslipidemia (DL) is closely related to osteoporosis (OP), while the exact common
      genetic mechanisms are still largely unknown. We proposed to use novel genetic
      analysis methods with pleiotropic information to identify potentially novel
      and/or common genes for the potential shared pathogenesis associated with OP
      and/or DL. We assessed the pleiotropy between plasma lipid (PL) and femoral neck
      bone mineral density (FNK BMD). We jointly applied the conditional false
      discovery rate (cFDR) method and the genetic analysis incorporating pleiotropy
      and annotation (GPA) method to the summary statistics provided by genome-wide
      association studies (GWASs) of FNK BMD (n = 49,988) and PL (n = 188,577) to
      identify potentially novel and/or common genes for BMD/PL. We found strong
      pleiotropic enrichment between PL and FNK BMD. Two hundred and forty-five PL SNPs
      were identified as potentially novel SNPs by cFDR and GPA. The corresponding
      genes were enriched in gene ontology (GO) terms "phospholipid homeostasis" and
      "chylomicron remnant clearance". Three SNPs (rs2178950, rs9939318, and rs9368716)
      might be the pleiotropic ones and the corresponding genes NLRC5 (rs2178950) and
      TRPS1 (rs9939318) were involved in NF-kappaB signaling pathway and Wnt signaling
      pathway as well as inflammation and innate immune processes. Our study validated
      the pleiotropy between PL and FNK BMD, and corroborated the reliability and high
      efficiency of cFDR and GPA methods in further analyses of existing GWASs with
      summary statistics. We identified potentially common and/or novel genes for PL
      and/or FNK BMD, which may provide new insight and direction for further research.

PMID- 29327332
TI  - Salience from multiple feature contrast: Evidence from saccade trajectories.
AB  - We used eye tracking to quantify the extent to which combinations of salient
      contrasts (orientation, luminance, and movement) influence a central salience map
      that guides eye movements. We found that luminance combined additively with
      orientation and movement, suggesting that the salience system processes luminance
      somewhat independently of the two other features. On the other hand, orientation
      and movement together influenced salience underadditively, suggesting that these
      two features are processed nonindependently. This pattern of results suggests
      that the visual system does not sum sources of salience linearly, but treats some
      sources of salience as redundant.

PMID- 29327333
TI  - Streptomyces flavalbus sp. nov., an actinobacterium isolated from rhizosphere of
      maize (Zea mays L.).
AB  - A novel actinobacterium, designated strain NEAU-QY24T, was isolated from the
      rhizosphere of corn (Zea mays L.). A polyphasic approach was employed to
      determine the taxonomic status of strain NEAU-QY24T. The isolate was found to
      have chemical and morphological properties of the genus Streptomyces, with high
      16S rRNA gene sequence similarity to Streptomyces lanatus JCM 4332T (98.3%) and
      clustered phylogenetically with Streptomyces lannensis JCM 16578T (98.2%). The
      cell wall was found to contain meso-diaminopimelic acid and the whole cell sugars
      were identified as glucose and ribose. The predominant menaquinones were
      identified as MK-9(H6), MK-9(H4) and MK-9(H8). The phospholipid profile was found
      to consisted of diphosphatidylglycerol, phosphatidylethanolamine and
      phosphatidylinositol. The major fatty acids were identified as iso-C16:0, C16:0,
      anteiso-C17:0 and C15:0. A combination of DNA-DNA hybridization experiments and
      phenotypic tests were carried out between strain NEAU-QY24T and its closely
      related strains, which clarified their relatedness and demonstrated that strain
      NEAU-QY24T could be distinguished from these strains. These data indicate that
      the isolate should be recognised as a new species of the genus Streptomyces, for
      which the name Streptomyces flavalbus sp. nov. is proposed. The type strain is
      NEAU-QY24T (= CGMCC 4.7400T = DSM 104539T).

PMID- 29327334
TI  - A masked least-squares smoothing procedure for artifact reduction in scanning-EMG
      recordings.
AB  - Scanning-EMG is an electrophysiological technique in which the electrical
      activity of the motor unit is recorded at multiple points along a corridor
      crossing the motor unit territory. Correct analysis of the scanning-EMG signal
      requires prior elimination of interference from nearby motor units. Although the
      traditional processing based on the median filtering is effective in removing
      such interference, it distorts the physiological waveform of the scanning-EMG
      signal. In this study, we describe a new scanning-EMG signal processing algorithm
      that preserves the physiological signal waveform while effectively removing
      interference from other motor units. To obtain a cleaned-up version of the
      scanning signal, the masked least-squares smoothing (MLSS) algorithm recalculates
      and replaces each sample value of the signal using a least-squares smoothing in
      the spatial dimension, taking into account the information of only those samples
      that are not contaminated with activity of other motor units. The performance of
      the new algorithm with simulated scanning-EMG signals is studied and compared
      with the performance of the median algorithm and tested with real scanning
      signals. Results show that the MLSS algorithm distorts the waveform of the
      scanning-EMG signal much less than the median algorithm (approximately 3.5 dB
      gain), being at the same time very effective at removing interference components.
      Graphical Abstract The raw scanning-EMG signal (left figure) is processed by the
      MLSS algorithm in order to remove the artifact interference. Firstly, artifacts
      are detected from the raw signal, obtaining a validity mask (central figure) that
      determines the samples that have been contaminated by artifacts. Secondly, a
      least-squares smoothing procedure in the spatial dimension is applied to the raw
      signal using the not contaminated samples according to the validity mask. The
      resulting MLSS-processed scanning-EMG signal (right figure) is clean of artifact
      interference.

PMID- 29327335
TI  - Classification and characterization of postural transitions using instrumented
      shoes.
AB  - The frequency and quality of sit-to-stand and stand-to-sit postural transitions
      decrease with age and are highly relevant for fall risk assessment. Accurate
      classification and characterization of these transitions in daily life of older
      adults are therefore needed. In this study, we propose to use instrumented shoes
      for postural transition classification as well as transition duration estimation
      from insole force signals. In the first part, data were collected with 10 older
      adults and 10 young participants performing transitions in the laboratory while
      wearing the instrumented shoes, without arm assistance. A wavelet approach was
      used to transform the insole force data, and candidate events were selected for
      transition duration estimation. Transition durations were then validated against
      a model based on force plate reference. Vertical force estimation was also
      compared to force plate measurement. In the second part, postural transitions
      were classified in daily life using the instrumented shoes and validated against
      a highly accurate wearable system. Transition duration was estimated with an
      error ranging from 10 to 20% while the error for vertical force estimation was
      7%. Postural transition classification was achieved with excellent sensitivity
      and precision exceeding 90%. In conclusion, the instrumented shoes are suitable
      for classifying and characterizing postural transitions in daily life conditions
      of healthy older adults. Graphical abstract "Experimental setup showing
      instrumented shoes, reference force plate, as well as IMUs used for postural
      transition classification and duration estimation comparison".

PMID- 29327337
TI  - Generalized nonmotor (absence) seizures-What do absence, generalized, and
      nonmotor mean?
AB  - OBJECTIVE: Clinical absences are now classified as "generalized nonmotor
      (absence) seizures" by the International League Against Epilepsy (ILAE). The aim
      of this paper is to critically review the concept of absences and to put the
      accompanying focal and motor symptoms into the context of the emerging
      pathophysiological knowledge. METHODS: For this narrative review we performed an
      extensive literature search on the term "absence," and analyzed the plethora of
      symptoms observed in clinical absences. RESULTS: Arising from the localization
      and the involved cortical networks, motor symptoms may include bilateral mild
      eyelid fluttering and mild myoclonic jerks of extremities. These motor symptoms
      may also occur unilaterally, analogous to a focal motor seizure with Jacksonian
      march. Furthermore, electroencephalography (EEG) abnormalities may exhibit
      initial frontal focal spikes and consistent asymmetries. Electroclinical
      characteristics support the cortical focus theory of absence seizures.
      Simultaneous EEG/functional magnetic resonance imaging (fMRI) measurements
      document cortical deactivation and thalamic activation. Cortical deactivation is
      related to slow waves and disturbances of consciousness of varying degrees. Motor
      symptoms correspond to the spike component of the 3/s spike-and-wave-discharges.
      Thalamic activation can be interpreted as a response to overcome cortical
      deactivation. Furthermore, arousal reaction during drowsiness or sleep triggers
      spikes in an abnormally excitable cortex. An initial disturbance in arousal
      mechanisms ("dyshormia") might be responsible for the start of this abnormal
      sequence. SIGNIFICANCE: The classification as "generalized nonfocal and nonmotor
      (absence) seizure" does not covey the complex semiology of a patient's clinical
      events.

PMID- 29327338
TI  - National norms for the expanded version of the inventory of depression and
      anxiety symptoms (IDAS-II).
AB  - OBJECTIVES: The present study developed normative data for the expanded version
      of the Inventory of Depression and Anxiety Symptoms (IDAS-II). The IDAS-II is a
      self-report measure containing 18 factor-analytically derived scales, each
      assessing a specific symptom of internalizing disorders, including depression,
      anxiety disorders, OCD, bipolar disorder, and PTSD. These normative data were
      used to examine group differences in internalizing symptoms across demographic
      characteristics. METHOD: A total of 1,836 Mechanical Turk users (47.6% male; mean
      age = 35.6) completed the IDAS-II; the sample was weighted to be representative
      of the U.S. population on gender, age, and race/ethnicity. RESULTS: Percentiles
      were derived for each of the IDAS-II scales. Age was the demographic
      characteristic most consistently associated with lower internalizing symptoms.
      CONCLUSIONS: The present study provides information on the distribution of
      specific internalizing symptoms in a large national sample, as well as on how
      these symptoms are related to demographic characteristics.

PMID- 29327336
TI  - Simultaneous utilization of multiple cues in judgments of learning.
AB  - There is much evidence that metacognitive judgments, such as people's predictions
      of their future memory performance (judgments of learning, JOLs), are inferences
      based on cues and heuristics. However, relatively little is known about whether
      and when people integrate multiple cues in one metacognitive judgment or focus on
      a single cue without integrating further information. The current set of
      experiments systematically addressed whether and to what degree people integrate
      multiple extrinsic and intrinsic cues in JOLs. Experiment 1 varied two cues:
      number of study presentations (1 vs. 2) and font size (18 point vs. 48 point).
      Results revealed that people integrated both cues in their JOLs. Experiment 2
      demonstrated that the two word characteristics concreteness (abstract vs.
      concrete) and emotionality (neutral vs. emotional) were integrated in JOLs.
      Experiment 3 showed that people integrated all four cues in their JOLs when
      manipulated simultaneously. Finally, Experiment 4 confirmed integration of three
      cues that varied on a continuum rather than in two easily distinguishable levels.
      These results demonstrate that people have a remarkable capacity to integrate
      multiple cues in metacognitive judgments. In addition, our findings render an
      explanation of cue effects on JOLs in terms of demand characteristics
      implausible.

PMID- 29327339
TI  - Electronic registry for the management of childhood obesity in Greece.
AB  - BACKGROUND: Obesity in childhood and adolescence represents a major health
      problem in our century. In Greece, more than 30%-35% of children and adolescents
      are either overweight or obese. MATERIALS AND METHODS: Using information and
      communication technologies, we developed a "National Registry for the Prevention
      and Management of Overweight and Obesity in Childhood and Adolescence" for
      guidance and training of Pediatricians and General Practitioners. The application
      supports interoperability with other national infrastructures and multi-layered
      security spanning preventive, detective and administrative controls. The Patient
      Summary Dataset includes information on medical history, family history,
      medications, immunizations, clinical examination and laboratory findings and
      appointment booking service. RESULTS: The application was launched in September
      2015 and is accessible by: http://app.childhood-obesity.gr/. Based on the data
      that the doctor registers, the system calculates a personalized therapeutic
      algorithm that provides information on diet, physical exercise and sleep, as well
      as guidance on laboratory investigations and referral to specialized centres. A
      pilot study performed in 1270 children and adolescents indicated that using this
      system resulted in a reduction in obesity rates by 30% and overweight rates by
      35% within 1 year. CONCLUSIONS: This National e-Health System appears to be
      effective in the management of overweight and obesity in childhood and
      adolescence.

PMID- 29327341
TI  - Combined thoracic paravertebral and pectoral nerve blocks for breast surgery
      under sedation: a prospective observational case series.
AB  - Avoidance of general anaesthesia for breast surgery may be because of clinical
      reasons or patient choice. There is emerging evidence that the use of regional
      anaesthesia and the avoidance of volatile anaesthetics and opioid analgesia may
      have beneficial effects on oncological outcomes. We conducted a prospective
      observational case series of 16 breast cancer surgeries performed under thoracic
      paravertebral plus pectoral nerve block with propofol sedation to demonstrate
      feasibility of technique, patient acceptability and surgeon satisfaction. Fifteen
      out of 16 cases were successfully completed under sedation and regional
      anaesthesia, with one conversion to general anaesthesia. Eleven out of 16 cases
      required low-dose intra-operative opioid analgesia. Out of the 15 surgical
      procedures completed under regional anaesthesia with sedation, all patients
      experienced either no or minimal intra-operative pain, and all would choose this
      anaesthetic technique again. Surgeon-reported operating conditions were
      'indistinguishable from general anaesthesia' in most cases, and surgeons were
      'extremely satisfied' or 'satisfied' with the technique after every procedure.
      Combined thoracic paravertebral plus pectoral nerve block with intra-operative
      sedation is a feasible technique for breast surgery.

PMID- 29327340
TI  - Shank3-deficient thalamocortical neurons show HCN channelopathy and alterations
      in intrinsic electrical properties.
AB  - KEY POINTS: Shank3 increases the HCN channel surface expression in heterologous
      expression systems. Shank3Delta13-16 deficiency causes significant reduction in
      HCN2 expression and Ih current amplitude in thalamocortical (TC) neurons.
      Shank3Delta13-16 - but not Shank3Delta4-9 -deficient TC neurons share changes in
      basic electrical properties which are comparable to those of HCN2-/- TC neurons.
      HCN channelopathy may critically mediate events downstream from Shank3
      deficiency. ABSTRACT: SHANK3 is a scaffolding protein that is highly enriched in
      excitatory synapses. Mutations in the SHANK3 gene have been linked to
      neuropsychiatric disorders especially the autism spectrum disorders. SHANK3
      deficiency is known to cause impairments in synaptic transmission, but its
      effects on basic neuronal electrical properties that are more localized to the
      soma and proximal dendrites remain unclear. Here we confirmed that in
      heterologous expression systems two different mouse Shank3 isoforms, Shank3A and
      Shank3C, significantly increase the surface expression of the mouse
      hyperpolarization-activated, cyclic-nucleotide-gated (HCN) channel. In
      Shank3Delta13-16 knockout mice, which lack exons 13-16 in the Shank3 gene (both
      Shank3A and Shank3C are removed) and display a severe behavioural phenotype, the
      expression of HCN2 is reduced to an undetectable level. The thalamocortical (TC)
      neurons from the ventrobasal (VB) complex of Shank3Delta13-16 mice demonstrate
      reduced Ih current amplitude and correspondingly increased input resistance,
      negatively shifted resting membrane potential, and abnormal spike firing in both
      tonic and burst modes. Impressively, these changes closely resemble those of HCN2
      /- TC neurons but not of the TC neurons from Shank3Delta4-9 mice, which lack
      exons 4-9 in the Shank3 gene (Shank3C still exists) and demonstrate moderate
      behavioural phenotypes. Additionally, Shank3 deficiency increases the ratio of
      excitatory/inhibitory balance in VB neurons but has a limited impact on the
      electrical properties of connected thalamic reticular (RTN) neurons. These
      results provide new understanding about the role of HCN channelopathy in
      mediating detrimental effects downstream from Shank3 deficiency.

PMID- 29327343
TI  - Changes in out-of-pocket charges associated with obstetric care provided under
      Medicare in Australia.
AB  - Recent health reforms alongside unregulated provider fees have led to increased
      attention being given to out-of-pocket healthcare costs. This study utilised
      annual statistics published by the Department of Health for services provided
      under the Medicare Benefits Schedule (MBS) from 1992/3 to 2016/17 to identify
      changes in out-of-pocket charges for obstetric items over time, and estimate the
      change in demand for obstetric items in response to price increases. Since 1992/3
      out-of-pocket charges increased by 1035% for out-of-hospital items and 77% for in
      hospital items. Demand for obstetric items has reduced with increasing charges.

PMID- 29327342
TI  - Reduced lysosomal clearance of autophagosomes promotes survival and colonization
      of Helicobacter pylori.
AB  - Evasion of autophagy is key for intracellular survival of bacteria in host cells,
      but its involvement in persistent infection by Helicobacter pylori, a bacterium
      identified to invade gastric epithelial cells, remains obscure. The aim of this
      study was to functionally characterize the role of autophagy in H. pylori
      infection. Autophagy was assayed in H. pylori-infected human gastric epithelium
      and the functional role of autophagy was determined via genetic or
      pharmacological ablation of autophagy in mouse and cell line models of H. pylori
      infection. Here, we showed that H. pylori inhibited lysosomal function and
      thereby promoted the accumulation of autophagosomes in gastric epithelial cells.
      Importantly, inhibiting autophagosome formation by pharmacological inhibitors or
      genetic ablation of BECN1 or ATG5 reduced H. pylori intracellular survival,
      whereas inhibition of lysosomal functions exerted an opposite effect. Further
      experiments demonstrated that H. pylori inhibited lysosomal acidification and the
      retrograde trafficking of mannose-6-phosphate receptors, both of which are known
      to positively regulate lysosomal function. We conclude that H. pylori subverts
      autophagy into a pro-survival mechanism through inhibition of lysosomal clearance
      of autophagosomes. Disruption of autophagosome formation offers a novel strategy
      to reduce H. pylori colonization in human stomachs. Copyright (c) 2018
      Pathological Society of Great Britain and Ireland. Published by John Wiley &
      Sons, Ltd.

PMID- 29327344
TI  - Quality of fresh-cut products as affected by harvest and postharvest operations.
AB  - There is a rising demand for fresh-cut convenience products with high quality and
      nutritional standards that needs to be met by the fresh-cut industry. It is well
      known that harvest and postharvest handling of fresh produce has a paramount
      impact on its quality and storage, although most of the existing literature has
      focused on these impacts related only to fresh produce that is destined for the
      final consumers. Indeed, current harvest methods and postharvest technologies
      have improved fruit and vegetable handling and distribution processes by slowing
      down physiological processes and senescence. Nonetheless, these technologies and
      methods may influence the quality of fresh produce as raw material for fresh-cut
      processing as a result of the dynamic responses of fresh produce to handling
      procedures and treatments. Here, we review the existing literature on the
      challenges facing the fresh-cut industry, focusing on the impact of harvest,
      maturity, and handling of fruit and vegetables on the quality of raw materials,
      as well as the implications for fresh-cut products. The review also highlights
      areas for further research with the aim of enhancing the sensorial, nutritional
      and biochemical quality of such products. (c) 2018 Society of Chemical Industry.

PMID- 29327346
TI  - Erratum.

PMID- 29327345
TI  - Serum lipoprotein (a) predicts acute coronary syndromes in patients with severe
      carotid stenosis.
AB  - BACKGROUND: Different cut-off values of serum lipoprotein (a) [Lp (a)] were
      recently identified to better stratify cardiovascular risk categories. Both
      pathophysiological and prognostic values of Lp (a) remain unclear. MATERIALS AND
      METHODS: Here, the prognostic value of Lp (a) and its correlation with
      intraplaque features were assessed in patients with severe carotid artery
      stenosis undergoing endarterectomy (n = 180). The cut-off value of 10 mg/dL for
      serum Lp (a) was selected to predict 24-month follow-up acute coronary syndrome
      (ACS). In addition, the association between serum Lp (a) and intraplaque lipids,
      collagen, inflammatory and vascular cells was assessed. Serum Lp (a) levels were
      measured by nephelometric assay. RESULTS: Patients with high Lp (a) had similar
      comorbidities, medications and laboratory parameters as compared to low Lp (a)
      levels. At 24-month follow-up, patients with high Lp (a) had more ACS as compared
      to low levels. Histological parameters within plaques were comparable in the
      study groups. No significant correlation between Lp (a) serum levels and
      intraplaque parameters was found, except for a weak positive association with
      smooth muscle cells in upstream plaque portions. When adjusted for gender, the
      presence of dyslipidaemia and chronic coronary artery disease, Lp (a) >=10 mg/dL
      remained predictive for ACS. CONCLUSIONS: Lp (a) determination could be a useful
      tool to predict ACS in patients with severe carotid stenosis.

PMID- 29327347
TI  - Unique anti-myeloma activity by thiazolidine-2,4-dione compounds with Pim
      inhibiting activity.
AB  - Proviral Integrations of Moloney virus 2 (PIM2) is overexpressed in multiple
      myeloma (MM) cells, and regarded as an important therapeutic target. Here, we
      aimed to validate the therapeutic efficacy of different types of PIM inhibitors
      against MM cells for their possible clinical application. Intriguingly, the
      thiazolidine-2,4-dione-family compounds SMI-16a and SMI-4a reduced PIM2 protein
      levels and impaired MM cell survival preferentially in acidic conditions, in
      contrast to other types of PIM inhibitors, including AZD1208, CX-6258 and PIM447.
      SMI-16a also suppressed the drug efflux function of breast cancer resistance
      protein, minimized the sizes of side populations and reduced in vitro colony
      forming capacity and in vivo tumourigenic activity in MM cells, suggesting
      impairment of their clonogenic capacity. PIM2 is known to be subject to
      ubiquitination-independent proteasomal degradation. Consistent with this, the
      proteasome inhibitors bortezomib and carfilzomib increased PIM2 protein levels in
      MM cells without affecting its mRNA levels. However, SMI-16a mitigated the PIM2
      protein increase and cooperatively enhanced anti-MM effects in combination with
      carfilzomib. Collectively, the thiazolidine-2,4-dione-family compounds SMI-16a
      and SMI-4a uniquely reduce PIM2 protein in MM cells, which may contribute to
      their profound efficacy in addition to their immediate kinase inhibition. Their
      combination with proteasome inhibitors is envisioned.

PMID- 29327349
TI  - Status of the Trait Concept in Contemporary Personality Psychology: Are the Old
      Questions Still the Burning Questions?
AB  - This special issue of Journal of Personality addresses one of the cardinal
      concerns of personality psychology, namely, the status of traits in contemporary
      personality science. Trait theory is a major scientific model for personality
      explanation and research. Although there have been critiques of traits, typically
      formulated from the point of view of the social-cognitive perspective, the trait
      approach can be viewed as a continuously developing paradigm. However,
      personality psychology persists in tackling burning questions concerning the
      status of traits that need to be answered. Modern trait approaches confront
      problems such as constructing an objective personality traits assessment,
      connecting the descriptive traits with explanatory processes, applying traits for
      understanding the individual person, clarifying the relation of traits to
      behavior, and using traits for solving cardinal concerns of personality
      psychology (e.g., personality organization). This special issue presents examples
      of contemporary trait theories that attempt to provide possible solutions to
      these issues and/or delineate other main issues to be resolved by future research
      and theorizing. We have asked contributors to portray their approach and describe
      in what way their trait theory continues a historic tradition and in what respect
      it breaks with the past and moves trait models to more mature scientific levels.

PMID- 29327350
TI  - Adopting innovation in gynaecology: The introduction of e-consult.
AB  - OBJECTIVE: To describe the development of an e-consultation service as part of
      the triaging and grading process of referrals and to report on the efficacy and
      safety of such a service. METHODS: All gynaecology e-consults in the study period
      June 2015 to March 2016 were retrospectively reviewed. The outcomes of interest
      were the initial reduction in first face-to-face hospital visits, and the rate of
      re-referrals. Acute admission for the same reason, a subsequent diagnosis of
      underlying (pre)-malignancy, or patient death from the condition related to the
      index referral were selected as measures for patient safety. RESULTS: Seven
      thousand and forty-two (7042) referrals were made to the gynaecology service in
      the 10 month study period. After exclusion of referrals to colposcopy and the
      early pregnancy clinic, 4738 e-referrals remained. Of these, 1013 referrals
      (21.4%) were triaged for an e-consult. One hundred and forty-seven patients
      (14.5%) with an initial e-consult were re-referred within 6 months for the same
      condition. The reduction in face-to-face contacts was 18.2% (866/4738). No death
      and/or acute admission for the same reason as stated in the initial referral
      occurred among the patients with e-consultation and none were later diagnosed
      with an underlying (pre)-malignancy. CONCLUSION: E-consultation was effective at
      reducing the number of first outpatient face-to-face contacts without notable
      compromise of the quality of care or patient safety. E-consultation allows
      specialists to provide expert clinical guidance, management and support to the
      referring provider when appropriate. Topics for further study include patient
      benefits and satisfaction, and further assessment of the social, economic and
      financial impacts on all parties involved.

PMID- 29327348
TI  - Respiratory dysfunction progresses with age in Kcna1-null mice, a model of sudden
      unexpected death in epilepsy.
AB  - OBJECTIVE: Increased breathing rate, apnea, and respiratory failure are
      associated with sudden unexpected death in epilepsy (SUDEP). We recently
      demonstrated the progressive nature of epilepsy and mortality in Kcna1-/- mice, a
      model of temporal lobe epilepsy and SUDEP. Here we tested the hypothesis that
      respiratory dysfunction progresses with age in Kcna1-/- mice, thereby increasing
      risk of respiratory failure and sudden death (SD). METHODS: Respiratory
      parameters were determined in conscious mice at baseline and following increasing
      doses of methacholine (MCh) using noninvasive airway mechanics (NAM) systems.
      Kcna1+/+ , Kcna1+/- , and Kcna1-/- littermates were assessed during 3 age ranges
      when up to ~30%, ~55%, and ~90% of Kcna1-/- mice have succumbed to SUDEP:
      postnatal day (P) 32-36, P40-46, and P48-56, respectively. Saturated arterial O2
      (SaO2 ) was determined with pulse oximetry. Lung and brain tissues were isolated
      and Kcna1 gene and protein expression were evaluated by reverse transcriptase
      quantitative polymerase chain reaction (RT-qPCR) and Western blot techniques.
      Airway smooth muscle responsiveness was assessed in isolated trachea exposed to
      MCh. RESULTS: Kcna1-/- mice experienced an increase in basal respiratory drive,
      chronic oxygen desaturation, frequent apnea-hypopnea (A-H), an atypical breathing
      sequence of A-H-tachypnea-A-H, increased tidal volume, and hyperventilation
      induced by MCh. The MCh-provoked hyperventilation was dramatically attenuated
      with age. Of interest, only Kcna1-/- mice developed seizures following exposure
      to MCh. Seizures were provoked by lower concentrations of MCh as Kcna1-/- mice
      approached SD. MCh-induced seizures experienced by a subset of younger Kcna1-/-
      mice triggered death. Respiratory parameters of these younger Kcna1-/- mice
      resembled older near-SD Kcna1-/- mice. Kcna1 gene and protein were not expressed
      in Kcna1+/+ and Kcna1+/- lungs, and MCh-mediated airway smooth muscle
      contractions exhibited similar half-maximal effective concentration( EC50 ) in
      isolated Kcna1+/+ and Kcna1-/- trachea. SIGNIFICANCE: The Kcna1-/- model of SUDEP
      exhibits progressive respiratory dysfunction, which suggests a potential
      increased susceptibility for respiratory failure during severe seizures that may
      result in sudden death.

PMID- 29327351
TI  - Negotiating inter-professional interaction: playing the general practitioner
      pharmacist game.
AB  - Despite a mutual interest in optimising the benefits of medication for patients,
      the general practitioner (GP) and community pharmacist (CP) often work in
      isolation from one another, both physically and figuratively. Sources of tension
      include pharmacy's 'shopkeeper' image, traditional medical hierarchies and
      potential encroachment on professional boundaries. This article examines GP and
      CP perceptions of their interactions and negotiations and, drawing on the works
      of Stein and Goffman, identifies a set of 'unwritten' rules, termed the 'GP
      pharmacist game', which involves the concept of 'face-work'. Qualitative
      interviews with 20 GPs and 23 CPs located in four geographically and
      demographically different areas in England were conducted during 2010-11. Key
      rules of the game include the pharmacist avoiding blaming the GP, using
      discretion in front of patients, and balancing the necessity and frequency of the
      communication. This article argues that whilst adhering to the 'GP-pharmacist
      game' may avoid conflict and 'get the job done', it may also constrain efforts to
      meet wider health care policy aims of a more collaborative relationship.

PMID- 29327352
TI  - Ultrasound findings provide clues to investigate founder mutations expressed as
      runs of homozygosity in chromosomal microarray studies.
AB  - OBJECTIVES: Chromosomal microarray analysis is effectively applied prenatally to
      detect copy number changes. Single nucleotide polymorphism (SNP) probes included
      in the microarray platform can detect regions of excessive homozygosity and
      identical-by-descent genomic stretches. The utility of the latter as part of
      prenatal diagnosis is not well established. Recessive founder mutations are well
      recognized within distinct ethnic groups. Combining these data with prenatal
      sonography provides accurate focused molecular diagnoses quickly. We aimed to
      evaluate the application of this approach in expectant families presenting to our
      unit. METHODS: Three unrelated gravidae presenting with specific fetal
      sonographic findings: (1) ventriculomegaly with encephalocele; (2) severe
      polyhydramnion; and (3) enlarged echogenic kidneys, underwent amniocentesis for
      chromosomal microarray analysis, and genome-wide human SNP array was used to
      analyze DNA from amniocytes. The Genomic Oligoarray and SNP array evaluation tool
      v3.0(c) was used to detect recessive loci associated with the reported clinical
      findings. Candidate genes were further interrogated using the Israeli National
      Genetic Database (INGD) and specifically searching and identifying a
      corresponding founder mutation within the defined ethnic group. RESULTS: Three
      fetuses from 3 distinct nuclear families in which the parents shared a similar
      ethnicity (either Ashkenazi or Bukharan Jews) albeit no reported consanguinity
      were assessed. We found no copy number changes; however, by evaluating regions of
      homozygosity, we were able to reveal relevant candidate gene for the specific
      phenotype for each fetus. Using the INGD led to targeted testing of a specific
      homozygous fetal mutation for which parents were found to be carriers. In the
      fetus with ventriculomegaly with encephalocele c.1167dupA mutation in the FKTN
      gene, in the fetus with severe polyhydramnion c.167ins6[TTTCCC] mutation in the
      BSND gene, and in the fetus with enlarged echogenic kidneys, c.3761_3762delCCinsG
      in the PKHD1 gene were identified. CONCLUSIONS: A tripartite approach integrating
      sonographic pathology with regions of excessive homozygosity data and INGD-based
      founder mutation repository yields a comprehensive streamlined approach to
      provide accurate genetic diagnosis and counselling within the time constraints of
      an ongoing pregnancy.

PMID- 29327353
TI  - Increased risk of congestive heart failure in patients with acetaminophen
      poisoning: A nationwide cohort study.
AB  - Acetaminophen poisoning increases cytochrome P450 2E1 expression and reactive
      oxygen species production, which may lead to maladaptive myocardial remodeling
      and congestive heart failure (CHF). We conducted a nationwide cohort study to
      investigate the incidence and risk of CHF in patients with acetaminophen
      poisoning. We identified a cohort of adult patients with newly diagnosed
      acetaminophen poisoning in the inpatient claims of the Taiwan National Health
      Insurance Research Database for the 1998-2011 period. A comparison cohort was
      frequency matched at a 4:1 ratio for sex, age and index year. All patients were
      followed up until the occurrence of CHF, withdrawal from the National Health
      Insurance program, or December 31, 2011. Cox proportional hazards models were
      employed to calculate the risk of CHF in the acetaminophen poisoning cohort
      compared with the comparison cohort, and the hazard ratios with 95% confidence
      intervals are presented. A total of 3546 and 14 184 patients with and without
      acetaminophen poisoning were followed up for a total of 25 856 and 102 119 person
      years, respectively. The overall incidence of CHF was higher in the acetaminophen
      poisoning cohort than in the comparison cohort (8.12 vs. 5.19 per 10 000 person
      years). After adjustment for covariates, the acetaminophen poisoning cohort
      exhibited a 1.59-fold higher risk of CHF (adjusted hazard ratio = 1.59; 95%
      confidence interval = 1.43-1.75) than did the comparison cohort. Patients with
      acetaminophen poisoning exhibited a significantly higher risk of CHF compared
      with the comparison cohort. Clinicians should follow up heart function in
      patients with acetaminophen poisoning.

PMID- 29327354
TI  - A validated liquid chromatography-high resolution-tandem mass spectrometry method
      for the simultaneous quantitation of tryptophan, kynurenine, kynurenic acid, and
      quinolinic acid in human plasma.
AB  - Tryptophan (TRP) catabolism via the kynurenine pathway is considered to represent
      a major link between inflammation and various diseases, including
      neurodegenerative disorders, depression, schizophrenia, multiple sclerosis,
      cardiovascular disease, and cancer. The kynurenine pathway and levels of TRP and
      its metabolites kynurenine (KYN), kynurenic acid (KYNA) and quinolinic acid
      (QUIN) are well regulated under physiological conditions but may be altered as
      part of the activated immune response. A simple, sensitive, and specific liquid
      chromatography-time of flight mass spectrometry method was developed for
      determining levels of the four compounds in human plasma samples. The workflow
      involves protein precipitation with acetonitrile, chromatographic separation on a
      Phenomenex Luna NH2 column by applying a linear 6 min gradient of 50-5%
      acetonitrile in aqueous ammonium acetate solution (5 mM, pH 9.5), and mass
      spectrometric detection with high-resolution tandem mass spectrometry. Charcoal
      treated plasma served as surrogate matrix for external standard calibration.
      Stable-isotope-labeled analogues were used as internal standards. The calibration
      ranges were 0.5-50 MUg/ml for TRP, 20-1000 ng/mL for KYN und QUIN, and 1-50 ng/mL
      for KYNA. Validation proved fitness of the developed workflow for the intended
      purpose. The established method was applied to the quantification of the four
      targets in 100 authentic plasma samples.

PMID- 29327355
TI  - Non-occupational allergic contact dermatitis caused by long-lasting nail polish
      kits for home use: 'the tip of the iceberg'.
AB  - BACKGROUND: Allergic contact dermatitis (ACD) from (meth)acrylates caused by long
      lasting nail polish (also known as "permanent", "semi-permanent" or "gel nail
      polish") has been described both in occupational and non-occupational settings.
      Inexpensive kits for home use have been available for purchase in many stores or
      through the Internet. OBJECTIVE: To report on several further cases of consumers
      sensitised to these nail products. METHODS: Patch test results and evaluation of
      ingredient labelling of products brought in by the patients. RESULTS: Four new
      cases are presented. Three of the patients reacted to 2-hydroxypropyl
      methacrylate, 2-hydroxyethyl methacrylate and ethyleneglycol dimethacrylate
      (EGDMA), and all 4 to 2-hydroxy ethylacrylate. CONCLUSIONS: Acrylates are present
      in a wide range of products including medical materials. Sensitization from
      (meth)acrylates caused by a merely aesthetic procedure might significantly impact
      health by jeopardizing access to several types of medical interventions. Policies
      should be implemented restricting the use of long-lasting nail polishes to
      qualified professionals and banning the indiscriminate sale of kits for home use.

PMID- 29327357
TI  - NIOSH and the use of systematic review methods in Occupational Safety and Health.

PMID- 29327356
TI  - Gene-Specific Variant Classifier (DPYD-Varifier) to Identify Deleterious Alleles
      of Dihydropyrimidine Dehydrogenase.
AB  - Deleterious variants in dihydropyrimidine dehydrogenase (DPD, DPYD gene) can be
      highly predictive of clinical toxicity to the widely prescribed chemotherapeutic
      5-fluorouracil (5-FU). However, there are very limited data pertaining to the
      functional consequences of the >450 reported no-synonymous DPYD variants. We
      developed a DPYD-specific variant classifier (DPYD-Varifier) using machine
      learning and in vitro functional data for 156 missense DPYD variants. The
      developed model showed 85% accuracy and outperformed other in silico prediction
      tools. An examination of feature importance within the model provided additional
      insight into functional aspects of the DPD protein relevant to 5-FU toxicity. In
      the absence of clinical data for unstudied variants, prediction tools like DPYD
      Varifier have great potential to individualize medicine and improve the clinical
      decision-making process.

PMID- 29327358
TI  - Opioid medication use in patients with gastrointestinal diagnoses vs unexplained
      gastrointestinal symptoms in the US Veterans Health Administration.
AB  - BACKGROUND: While opioid prescriptions have increased alarmingly in the United
      States (US), their use for unexplained chronic gastrointestinal (GI) pain (eg,
      irritable bowel syndrome) carries an especially high risk for adverse effects and
      questionable benefit. AIM: To compare opioid use among US veterans with
      structural GI diagnoses (SGID) and those with unexplained GI symptoms or
      functional GI diagnoses (FGID), a group for whom opioids have no accepted role.
      METHODS: Veterans Health Administration (VHA) administrative data from fiscal
      year 2012 were used to identify veterans with diagnostic codes recorded for SGID
      and FGID. This cohort study examined VHA pharmacy data to compare groups
      receiving >= 1 opioid prescription during the year and number of prescriptions
      filled. Bivariate and multiple logistic regression analyses adjusted for
      potential confounding factors (demographics, medical diagnoses, social factors)
      and identified potential mediators (service use, psychiatric comorbidity) of
      opioid use in these groups. RESULTS: A greater proportion of veterans with FGID
      received an opioid prescription during fiscal year 2012 (36.0% of 272 431)
      compared to only 28.9% of 1 223 744 in the SGID group (Relative Risk [RR] =
      1.25). In multivariate logistic regression, personality disorders and drug abuse
      (OR 1.23 for each group), recent homelessness (OR 1.22), psychotropic medication
      fills (OR 1.55) and emergency department encounters (OR 1.21) were independently
      associated with opioid prescription use. CONCLUSIONS: Despite the potential for
      adverse consequences, opioids more often are prescribed for veterans with
      chronic, unexplained GI symptoms compared to those with structural diagnoses.
      Psychiatric comorbidities and frequent healthcare encounters mediate some of the
      opioid use risk.

PMID- 29327360
TI  - Aboveground herbivory induced jasmonates disproportionately reduce plant
      reproductive potential by facilitating root nematode infestation.
AB  - Different plant feeders, including insects and parasitic nematodes, can influence
      each other by triggering systemic changes in their shared host plants. In most
      cases, however, the underlying mechanisms are unclear, and the consequences for
      plant fitness are not well understood. We studied the interaction between leaf
      feeding Manduca sexta caterpillars and root parasitic nematodes in Nicotiana
      attenuata. Simulated M. sexta attack increased the abundance of root parasitic
      nematodes in the field and facilitated Meloidogyne incognita reproduction in the
      glasshouse. Intact jasmonate biosynthesis was found to be required for both
      effects. Flower counts revealed that the jasmonate-dependent facilitation of
      nematode infestation following simulated leaf attack reduces the plant's
      reproductive potential to a greater degree than would be expected from the
      additive effects of the individual stresses. This work reveals that jasmonates
      mediate the interaction between a leaf herbivore and root parasitic nematodes and
      illustrates how plant-mediated interactions can alter plant's reproductive
      potential. The selection pressure resulting from the demonstrated fitness effects
      is likely to influence the evolution of plant defense traits in nature.

PMID- 29327361
TI  - Myocardial injury in fetal aortic stenosis: Insights from amniotic fluid
      analysis.
AB  - OBJECTIVE: Fetal aortic stenosis (AS) imposes pressure load on the developing
      left ventricle (LV) and leads to derangements in myocardial structure and
      function via mechanisms that are not well characterized. METHODS: We compared
      amniotic fluid NT-BNP and troponin levels in fetuses with AS prior to fetal
      valvuloplasty and controls. We estimated correlations between NT-BNP and fetal
      echo parameters and identify NT-BNP cutoff associated with biventricular outcome
      RESULTS: Median NT-BNP level was higher in fetal AS than controls (3858 vs 1737
      pg/mL, P < 0.012). By contrast, troponin levels were lower in fetal AS, with
      troponin > detectable in 0/25 (0%) AS cases compared with 22/85 (26%) controls (P
      = 0.03). Of 25 fetal AS cases, 12 (48%) had biventricular outcome. Fetuses with
      NT-BNP < 910 pg/mL were more likely to have biventricular (OR =10) compared with
      those >=910 pg/mL (P = 0.045). Higher NT-BNP correlated with earlier gestational
      age and measures of larger left heart size. CONCLUSION: NT-BNP is elevated in
      fetal AS, suggesting that LV pressure load and increased wall stress lead to
      maladaptive stretch-related myocardial remodeling. Troponin is normal in mid
      gestation fetal AS, suggesting that ischemia is not the primary factor in fetal
      response to LV pressure load.

PMID- 29327362
TI  - P-wave and interatrial block: New predictor for atrial high rate episodes in
      patients with cardiac implantable electronic devices.
AB  - BACKGROUND: The presence of interatrial block (IAB) is associated with the
      development of atrial fibrillation (AF). The aim of this study was to determine
      whether P-wave duration and presence of IAB before the implantation of a cardiac
      implantable electronic device (CIED) are associated with the presence of atrial
      high rate episodes (AHRE), during long-term follow-up. METHODS: 380 patients (57%
      men; 75 +/- 10 years) were included. IAB was defined according to the
      International Consensus Criteria. AHRE was defined as an episode of atrial rate
      >=225 beats/min with a minimum duration of 5 minutes. RESULTS: Documented
      paroxysmal AF before the implantation was present in 24% of the patients; 80% had
      hypertension and 32% structural heart disease. Mean P-wave duration was 123 +/-
      23 ms, and 39% of the patients had IAB (32% partial, 7% advanced). After a mean
      follow-up of 18 +/- 12 months, 33% of the patients presented AHRE. Patients with
      AHRE had a P-wave duration significantly longer (130 +/- 24 ms vs 119 +/- 21 ms;
      P < 0.001) and a greater prevalence of IAB (53% vs 32%; P < 0.001). In a
      multivariate analysis, predictors of AHRE were: IAB (odds ratio [OR] 2.1; 95%
      confidence interval [CI] [1.3-3.4], P < 0.001) and previous paroxysmal AF (OR
      2.6; 95% CI [1.5-4.3], P < 0.001). In patients without previous AF, the presence
      of IAB was also a significant predictor of AHRE (OR 3.1; 95% CI [1.8-5.5], P <
      0.001). CONCLUSIONS: IAB is a strong predictor of AHRE in patients with CIED.
      This finding is independent of the presence of prior paroxysmal AF.

PMID- 29327359
TI  - Contact sensitization in dental technicians with occupational contact dermatitis.
      Data of the Information Network of Departments of Dermatology (IVDK) 2001-2015.
AB  - BACKGROUND: Dental technicians (DTs) are at increased risk for allergic contact
      sensitization. OBJECTIVES: To assess the current spectrum of occupational
      sensitization in DTs with occupational contact dermatitis (OCD). METHODS: A
      retrospective analysis of Information Network of Departments of Dermatology patch
      test data from the years 2001-2015 concerning DTs with OCD was performed.
      RESULTS: Patients of the study group (226 DTs with OCD) were significantly more
      often diagnosed with allergic contact dermatitis (37.6% versus 18.5%; p = 0.0002)
      than patients of the control group (124 DTs without OCD). In the study group,
      positive reactions were most frequently observed to methacrylates and/or
      acrylates (n = 67). Of these, 61 patients showed positive reactions to at least
      one of the five most frequent allergens in this group, namely 2-hydroxyethyl
      methacrylate, 2-hydroxypropyl methacrylate, methyl methacrylate, ethyl
      methacrylate, and/or ethylene glycol dimethacrylate. In contrast, no positive
      reactions to diurethane dimethacrylate (DUDMA) occurred. Among allergens of the
      German Contact Dermatitis Research Group series 'dental metals', positive
      reactions were less frequent and were mainly to palladium chloride (n = 6).
      CONCLUSIONS: The present data analysis showed that the sensitization spectrum and
      spectrum of cross-reactivity are largely unchanged as compared with the 1990s. It
      can be concluded that test recommendations are still valid and useful, except for
      the methacrylate DUDMA, which could be omitted.

PMID- 29327364
TI  - 4-Phenylbutyric acid presents therapeutic effect on osteoarthritis via inhibiting
      cell apoptosis and inflammatory response induced by endoplasmic reticulum stress.
AB  - Osteoarthritis (OA) is a common bone and joint disease with a wild range of risk
      factors, which is associated with endoplasmic reticulum (ER) stress. The aim of
      our study was to discuss the possible mechanism of ER stress associated with OA
      in vivo and explore novel therapeutic method against OA. OA-induced damages in
      cartilage tissues were evaluated by HE, Safranin O/fast green, and TUNEL
      staining. The inflammatory factors concentration and the expression of FAP, MMP2,
      MMP9, Bax, Bcl-2, CHOP, and GRP78 were evaluated by ELISA, real-time PCR, and
      Western blot analyses. As results, 4-phenylbutyric acid (4-PBA)-treated OA
      cartilage tissues presented alleviated tissue damage with less apoptotic cells
      and cytokine production in comparison with advanced-OA tissues. Downregulation of
      Bax/Bcl-2, CHOP, GRP78, inflammatory factors, and reactive oxygen species
      generation, and the increase of MMP level detected after 4-PBA treatment
      indicated an inhibitory effect of 4-PBA on cell apoptosis, inflammatory response,
      and ER stress in OA. In conclusion, we indicate that ER stress causes cell
      apoptosis and inflammatory response, resulting in the tissue damage within OA. At
      the same time, 4-PBA exhibited protective effect on cartilage cells against OA
      through the inhibition of ER stress.

PMID- 29327363
TI  - Pretreatment with substance P alleviates irritation due to sodium lauryl sulphate
      exposure by maintaining E-cadherin expression on human keratinocytes.

PMID- 29327365
TI  - Millimeter spatial resolution in vivo sodium MRI of the human eye at 7 T using a
      dedicated radiofrequency transceiver array.
AB  - PURPOSE: The aim of this study was to achieve millimeter spatial resolution
      sodium in vivo MRI of the human eye at 7 T using a dedicated six-channel
      transceiver array. We present a detailed description of the radiofrequency coil
      design, along with electromagnetic field and specific absorption ratio
      simulations, data validation, and in vivo application. METHODS: Electromagnetic
      field and specific absorption ratio simulations were performed. Transmit field
      uniformity was optimized by using a multi-objective genetic algorithm. Transmit
      field mapping was conducted using a phase-sensitive method. An in vivo
      feasibility study was carried out with 3-dimensional density-adapted projection
      reconstruction imaging technique. RESULTS: Measured transmit field distribution
      agrees well with the one obtained from simulations. The specific absorption ratio
      simulations confirm that the radiofrequency coil is safe for clinical use. Our
      radiofrequency coil is light and conforms to an average human head. High spatial
      resolution (nominal 1.4 and 1.0 mm isotropic) sodium in vivo images of the human
      eye were acquired within scan times suitable for clinical applications (~ 10
      min). CONCLUSIONS: Three most important eye compartments in the context of sodium
      physiology were clearly delineated in all of the images: the vitreous humor, the
      aqueous humor, and the lens. Our results provide encouragement for further
      clinical studies. The implications for research into eye diseases including
      ocular melanoma, cataract, and glaucoma are discussed. Magn Reson Med 80:672-684,
      2018. (c) 2018 International Society for Magnetic Resonance in Medicine.

PMID- 29327366
TI  - Financing elderly people's long-term care needs: Evidence from China.
AB  - Confronted by accelerated population aging, China is establishing a long-term
      care (LTC) system. This study discusses challenges and recommendations for
      financing China's LTC system. On the basis of the data on elderly people's self
      care ability from the Chinese Longitudinal Healthy Longevity Survey, we calculate
      the size of the elderly population that need LTC for the period from 2015 to 2030
      and analyse the increasing tendency of LTC expenses by considering the impact of
      price increase. We also analyse the local governments' financial capacity for LTC
      support by comparing the expense level to the fiscal revenue. The study found
      that aging will double the LTC expenses by 2030. Therefore, this study suggests
      the establishment of an LTC insurance system that allocates LTC expenses, which
      are currently borne by individuals and families, more fairly among the
      government, individuals, and families. Moreover, with the current LTC reforms,
      implemented primarily by local governments in China, we believe that the central
      government should bear some of the fiscal responsibility by conducting fiscal
      transfers to partially support undeveloped regions that are establishing an LTC
      system.

PMID- 29327367
TI  - The free healthcare initiative in Sierra Leone: Evaluating a health system
      reform, 2010-2015.
AB  - This article presents the findings of a theory-based evaluation of the Sierra
      Leone Free Health Care Initiative (FHCI), using mixed methods. Analytical
      approaches included time-series analysis of national survey data to examine
      mortality and morbidity trends, as well as modelling of impact using the Lives
      Saved Tool and expenditure trend analysis. We find that the FHCI responded to a
      clear need in Sierra Leone, was well designed to bring about needed changes in
      the health system to deliver services to the target beneficiaries, and did indeed
      bring funds and momentum to produce important systemic reforms. However, its
      ambition was also a risk, and weaknesses in implementation have been evident in a
      number of core areas, such as drugs supply. We conclude that the FHCI was one
      important factor contributing to improvements in coverage and equity of coverage
      of essential services for mothers and children. Modelled cost-effectiveness is
      high-in the region of US$ 420 to US$ 444 per life year saved. The findings
      suggest that even-or perhaps especially-in a weak health system, a reform-like
      fee removal, if tackled in a systematic way, can bring about important health
      system gains that benefit vulnerable groups in particular.

PMID- 29327368
TI  - Measurement of residual chemical shift anisotropies in compressed
      polymethylmethacrylate gels. Automatic compensation of gel isotropic shift
      contribution.
AB  - Mechanical compression of polymer gels provides a simple way for the measurement
      of residual chemical shift anisotropies, which then can be employed, on its own,
      or in combination with residual dipolar couplings, for structural elucidation
      purposes. Residual chemical shift anisotropies measured using compression devices
      needed a posteriori correction to account for the increase of the polymer to
      solvent ratio inside the swollen gel. This correction has been cast before in
      terms of a single-free parameter which, as shown here, can be simultaneously
      optimized along with the components of the alignment tensor while still retaining
      discriminating power of the different relative configurations as illustrated in
      the stereochemical analysis of alpha-santonin and 10-epi-8-deoxycumambrin B.

PMID- 29327369
TI  - Overweight and obesity may play a role in the pathogenesis of chronic spontaneous
      urticaria.
AB  - BACKGROUND: Chronic spontaneous urticaria (CSU) is one of the commonest diseases
      in allergological and dermatological practice. It constitutes an
      interdisciplinary problem, and its pathogenesis is not always easily determined.
      It has been suggested that metabolic syndrome and hyperlipidaemia are more
      frequent in patients with CSU, but the influence of overweight and obesity on the
      development of CSU has not been thoroughly investigated. AIM: To assess the
      association between body parameters and the development of CSU. METHODS: The
      study enrolled 85 patients with CSU, who were divided into three subgroups:
      patients whose only symptoms were weals, patients whose only symptom was angio
      oedema, and patients with urticaria and accompanying angio-oedema. Mean weight,
      height, body mass index (BMI), body surface area, disease duration and age of
      disease onset were recorded RESULTS: There was a statistically significant
      association between CSU and heavier weight, higher BMI, greater affected body
      surface area and older age at disease onset. Subjects with higher BMI values had
      a tendency towards longer disease duration. There were no statistically
      significant differences between the three subgroups. CONCLUSIONS: Our results
      suggest that CSU, especially if of long duration, may be associated with
      overweight and obesity, while increased body mass can result in later onset of
      urticaria symptoms. Further analyses to confirm the presented results and
      possible association between obesity and CSU occurrence are needed.

PMID- 29327370
TI  - Role of immune system in tumor progression and carcinogenesis.
AB  - Tumor micro-environment has potential to customize the behavior of the immune
      cell according to their need. In immune-eliminating phase, immune cells eliminate
      transformed cells but after tumor establishment innate and adaptive immune cells
      synergistically provide shelter as well as fulfill their requirement that helps
      in progression. In between eliminating and establishment phase, equilibrium and
      escaping phase regulate the immune cells response. During immune-escaping, (1)
      the antigenic response generated is either inadequate, or focused entirely on
      tolerance, and (2) immune response generated is specific and effective, but the
      tumor skips immune recognition. In this review, we are discussing the critical
      role of immune cells and their cytokines before and after the establishment of
      tumor which might play a critical role during immunotherapy.

PMID- 29327371
TI  - Variable degrees of ventricular preexcitation during rapid atrial pacing: What is
      the mechanism?

PMID- 29327372
TI  - Relative short-term efficacy and acceptability of agomelatine versus vortioxetine
      in adult patients suffering from major depressive disorder.
AB  - Agomelatine and vortioxetine are antidepressants with different mechanisms of
      action compared to other pharmaceutical treatment options. The objective of this
      present analysis is to determine the relative efficacy and acceptability of
      agomelatine (25-50 mg) compared to vortioxetine (10-15-20 mg) in adult patients
      with major depressive disorder. We performed an adjusted indirect comparison
      using placebo as a common control. The main outcomes were efficacy (response to
      treatment by Montgomery-Asberg depression rating scale/Hamilton Rating Scale for
      Depression) and acceptability (withdrawal rate for any reason or due to adverse
      events). 10 agomelatine and 11 vortioxetine studies were included in the
      analysis. For efficacy, no difference was shown between agomelatine and
      vortioxetine (E[95% CI] = -0.03 [-0.12;0.05]). For acceptability, no significant
      difference was found between both antidepressants. These findings substantiate
      current understanding that most antidepressants are of similar average efficacy
      and tolerability. Such equivalent therapeutic benefit of both compounds, measured
      by a quantitative clinical research approach, has to be discussed with the
      knowledge of a qualitative estimation in routine practice.

PMID- 29327373
TI  - The UK's legal position on Animal Sentience.

PMID- 29327374
TI  - Dynamic coronary MR angiography in a pig model with hyperpolarized water.
AB  - PURPOSE: To investigate dynamic coronary MR angiography using hyperpolarized
      water as a positive contrast agent. Hyperpolarization can increase the signal by
      several orders of magnitude, and has recently been translated to human cardiac
      application. The aim was to achieve large 1 H signal enhancement to allow high
      resolution imaging of the coronary arteries. METHODS: Protons in D2 O were
      hyperpolarized by dissolution dynamic nuclear polarization. A total of 18 mL of
      hyperpolarized water was injected into the coronary arteries of healthy pigs (N =
      9; 3 injections in 3 animals). The MRI images were acquired with a gradient-echo
      sequence in an oblique slab covering the main left coronary arteries with 0.55 mm
      in-plane resolution. The acquisition time was 870 ms per frame. RESULTS: A more
      than 200-fold signal enhancement compared with thermally polarized water at 3 T
      was obtained. Coronary angiographic images with a signal-to-noise ratio from the
      left main stem of 269 +/- 169 and coronary sharpness from the proximal left
      anterior descending coronary artery of 0.31 +/- 0.086 mm-1 were obtained. Dynamic
      images were acquired over a 10 s time window. CONCLUSION: Hyperpolarized water MR
      angiography of the coronary arteries in a large animal model with high signal-to
      noise ratio and high spatial and temporal resolution was obtained. Magn Reson Med
      80:1165-1169, 2018. (c) 2018 International Society for Magnetic Resonance in
      Medicine.

PMID- 29327375
TI  - Impact of HIV/aids epidemic on human capital development in West Africa.
AB  - West Africa occupies the third position with respect to the burden of human
      immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) globally,
      after Southern and East Africa. About 5 million adults and children are infected
      with the disease in the subregion, while HIV prevalence in the general population
      hovers around 2% and 5%. This paper attempts to investigate the impact of
      HIV/AIDS epidemic on human capital development in 11 West African countries over
      the period 1990 to 2011. The study used a dynamic panel data modeling approach,
      using first difference, difference generalized methods of moment, and system
      generalized methods of moment estimating techniques. Four measures of HIV/AIDS
      and 2 human capital measures were used in the study. The findings revealed that
      HIV/AIDS pandemic had negative and significant impact on human capital in West
      Africa. However, the statistical significance was more pronounced on life
      expectancy (a measure of human capital), while the negative impact on school
      enrolment (another human capital measure) was not significant. It is therefore
      recommended that the spread of HIV/AIDS disease in West Africa should be
      effectively controlled, while the number of infected persons undergoing
      antiretroviral therapy in the subregion should be increased to a near 100%
      coverage.

PMID- 29327376
TI  - Urinary orosomucoid is associated with progressive chronic kidney disease stage
      in patients with sickle cell anemia.

PMID- 29327378
TI  - Comparing impact on the family and insurance coverage in children with cerebral
      palsy and children with another special healthcare need.
AB  - BACKGROUND: Families and caregivers of children with special healthcare needs
      (CSHCN) often experience financial difficulties, have unmet physical and mental
      health needs, and are at increased risk of marital problems due to the stress
      caused by carrying for their child. Within the larger population of CHSCN, young
      people with cerebral palsy (CP) have more unmet needs due to the complexity and
      potential severity of the disability. The purpose of this study was to identify
      factors associated with differences in insurance coverage and impact on the
      family of children with CP and other CHSCN. METHODS: The data were taken from the
      National Survey of Children with Special Health Care Needs, which was designed to
      examine state- and national-level estimates of CSHCN. Three variables examined
      differences in insurance coverage between those children diagnosed with CP versus
      all other CSHCN: insurance coverage for the previous year, current insurance
      coverage, and adequacy of insurance coverage. Four variables representing
      different indicators of family impact were used to assess differences between
      children with CP versus all other CSHCN: out-of-pocket expenses for healthcare,
      family financial burden, hours per week that family members spent caring for the
      child, and impact on family work life. RESULTS: The results of this study showed
      significant differences between households with a child with CP and a child with
      another health special need in terms of insurance coverage, indicating a tendency
      of children with CP to be insured the entire year. As for the impact on the
      family in households with children with CP versus other CSHCN, there were
      significant differences in all four variables that were analysed. CONCLUSIONS:
      There is limited evidence highlighting differences between the impact of caring
      for a child with CP and caring for other CSHCN. Caring for a child with CP has a
      significant impact on the family, despite insurance coverage.

PMID- 29327379
TI  - Influence of varying stem and metaphyseal sleeve size on the primary stability of
      cementless revision tibial trays used to reconstruct AORI IIA defects. A
      simulation study.
AB  - Traditionally, diaphyseal stems have been utilized to augment the stability of
      revision total knee replacement (rTKR) implants. More recently metaphyseal
      augments, such as sleeves, have been introduced to further augment component
      fixation. The effect of augments such as stems and sleeves have on the primary
      stability of a rTKR implant is poorly understood, however it has important
      implications on the complexity, costs and survivorship of the procedure. Finite
      element analysis was used to investigate the primary stability and strain
      distribution of various size stems and sleeves used in conjunction with a
      cementless revision tibial tray. The model was built from computer tomography
      images of a single healthy tibia obtained from an 81-year-old patient to which an
      Anderson Orthopaedic Research Institute (AORI) IIA defect was virtually added.
      The influences of varying body mass index (BMI) and bone modulus were also
      investigated. Stemless sleeves were found to provided adequate primary implant
      stability (average implant micro-motion <50 MUm) for the studied defect. Addition
      of a stem did not enhance the primary stability. Furthermore, this study found
      that varying BMI and bone modulus had a considerable effect on strain
      distribution but negligible effect on micro-motion in the sleeve area. In
      conclusion, the addition of diaphyseal stem to a metaphyseal sleeve had little
      benefit in enhancing the primary stability of tibial trays augmented when
      simulating reconstructions of AORI IIA tibial defects. Additional studies are
      required to determine the relative benefit of the diaphyseal stem when using
      metaphyseal sleeves defects with more extensive bone loss. (c) 2018 Orthopaedic
      Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1876-1886,
      2018.

PMID- 29327377
TI  - Sezary syndrome managed with histone deacetylase inhibitor followed by anti-CCR4
      monoclonal antibody.
AB  - A 70-year-old man presented to our clinic with a 10-year history of recurrent
      pruritic erythema and plaques on his trunk and limbs. Based on the pathological
      findings and monoclonal rearrangement of the T-cell receptor (TCR)-Cbeta1 gene,
      mycosis fungoides (T2N0M0B0 stage IB) was diagnosed. Despite combination therapy
      including histone deacetylase inhibitor (vorinostat), the symptoms slowly evolved
      into Sezary syndrome (SS; T4N1M0B2) over 4 years, with dense infiltrates due to
      atypical lymphocytes expressing CCR4 developing in the entire dermis. Anti-CCR4
      monoclonal antibody (mogamulizumab) treatment was started. After seven courses,
      the CCR4-positive atypical lymphocytes decreased in the dermis to levels below
      those seen at the outset of treatment. To our knowledge, there is no previous
      report of a case of SS managed with vorinostat followed by mogamulizumab
      demonstrating such a remarkable change in the pathological state following
      treatment.

PMID- 29327380
TI  - Effects of deficiency and surplus dietary threonine on reproductive performance
      of primiparous pregnant gilts.
AB  - Dietary threonine imbalance is known to impair reproductive performances of
      gestating sows, but the underlying mechanisms are largely unknown. In this study,
      effects of deficiency and surplus dietary threonine during gestation on
      reproductive performance, serum metabolites and hormones concentration, and
      colostral nutrient and immunoglobulin contents of primiparous sows were
      investigated. Ninety primiparous pregnant gilts were assigned to one of the three
      dietary treatments with different standardized ileal digestible threonine/lysine
      ratios at 0.59, 0.72 and 0.85, which represented deficient (DT), adequate (AT)
      and surplus (ST) dietary threonine concentration respectively. Maternal body
      weight gain from day 80-110 of gestation was highest (p < .05) for gilts fed AT
      than for gilts fed DT or ST. On days 30 and 110, serum threonine concentration
      increases in a dose-dependent manner with the increasing of dietary threonine
      concentration in (p < .01), serum urea nitrogen concentration was lower (p < .01)
      in gilts fed AT than DT or ST, and serum insulin-like growth factor-I (IGF-I) was
      lowest (p < .05) for gilts fed DT. On day 110, gilts fed AT had lower serum
      progesterone concentration but higher concentrations of serum prolactin (p < .05)
      compared to DT and ST. Concentration of colostral immunoglobulin A and G from
      gilts fed DT was lower (p < .05) compared with gilts fed AT or ST. In conclusion,
      gilts with the adequate threonine intake were more able to conserve dietary amino
      acids to support foetal and maternal tissue gain. Deficient or ST threonine
      intake may induce a delay in changes in progesterone and prolactin concentrations
      during the prepartum period impeding the transition from pregnancy to lactation.

PMID- 29327381
TI  - Oxidative stress impairs myocyte autophagy, resulting in myocyte hypertrophy.
AB  - NEW FINDINGS: What is the central question of this study? Does oxidative stress
      induce impairment of autophagy that results in myocyte hypertrophy early after
      pressure overload? What is the main finding and its importance? In cultured
      myocytes, hydrogen peroxide decreased autophagy and increased hypertrophy, and
      inhibition of autophagy enhanced myocyte hypertrophy. In rats with early
      myocardial hypertrophy after pressure overload, myocyte autophagy was
      progressively decreased. The antioxidant N-acetyl-cysteine or the superoxide
      dismutase mimic tempol prevented the decrease of myocyte autophagy and attenuated
      myocyte hypertrophy early after pressure overload. These findings suggest that
      oxidative stress impairs myocyte autophagy that results in myocyte hypertrophy.
      ABSTRACT: Insufficient or excessive myocyte autophagy is associated with left
      ventricular (LV) hypertrophy. Reactive oxygen species mediate myocyte hypertrophy
      in vitro and pressure overload-induced LV hypertrophy in vivo. In the present
      study, we tested the hypothesis that oxidative stress induces an impairment of
      autophagy that results in myocyte hypertrophy. H9C2 cardiomyocytes pretreated
      with the autophagy inhibitor 3-methyladenine were exposed to 10 and 50 MUm
      hydrogen peroxide (H2 O2 ) for 48 h. Male Sprague-Dawley rats underwent abdominal
      aortic constriction (AAC) or sham operation. The animals were killed 24, 48 or 72
      h after surgery. In a separate group, the AAC and sham-operated rats randomly
      received the antioxidant N-acetyl-cysteine or the superoxide dismutase mimic
      tempol for 72 h. In H9C2 cardiomyocytes, H2 O2 decreased the ratio of microtubule
      associated protein light chain 3 (LC3) II to LC3 I and increased P62 and
      phosphorylated ERK (p-ERK) proteins and myocyte surface area. 3-Methyladenine
      further increased H2 O2 -induced p-ERK expression. In rats after AAC, the heart
      to body weight ratio was progressively increased, the LC3 II/I ratio was
      progressively decreased, p62 and p-ERK expression was increased, and expression
      of Beclin1, Atg5 and Atg12 was decreased. N-Acetyl-cysteine or tempol prevented
      the decreases in the LC3 II/I ratio and Beclin1 and Atg5 expression and
      attenuated the increases in LV wall thickness, myocyte diameter and brain
      natriuretic peptide expression in AAC rats. In conclusion, oxidative stress
      decreases Beclin1 and Atg5 expression that results in impairment of autophagy,
      leading to myocyte hypertrophy. These findings suggest that antioxidants or
      restoration of autophagy might be of value in the prevention of early myocardial
      hypertrophy after pressure overload.

PMID- 29327382
TI  - Retrospective analysis of forward and reverse ABO typing discrepancies among
      patients and blood donors in a tertiary care hospital.
AB  - OBJECTIVE: The aim of our study was to determine the incidence and causes of ABO
      typing discrepancies among patients and blood donors at our centre. BACKGROUND:
      An accurate interpretation of the ABO blood group of an individual is of utmost
      importance to ensure patient safety and good transfusion practices. METHODS: A
      retrospective observational study was carried out in the Department of
      Transfusion Medicine in our hospital from March 2013 to December 2015. Records of
      all patient and blood donor samples were retrieved and analysed for ABO typing
      discrepancies. RESULTS: In total, 135 853 patient and 62 080 donor samples were
      analysed for ABO typing discrepancies. The incidence among patients and blood
      donors was found to be 0.1% (138/135853) and 0.02% (14/62080), respectively. The
      mean age for patients and blood donors was 48.4 and 29.2 years, respectively. The
      most common cause of ABO typing discrepancies was due to cold autoantibodies
      among the patients (50.7%) and blood donors (57%) causing discrepant results in
      reverse typing. The various other causes of reverse typing discrepancies among
      patients were weak/missing antibody (25.4%), cold-reacting alloantibody (4.3%),
      warm autoantibody (2.2%), anti-A1 antibody (2.2%), Bombay phenotype (1.5%),
      transplantation (0.7%) and rouleaux (0.7%), whereas in blood donors, the causes
      were cold-reacting antibody (7%) and weak antibody (7%). The major cause of
      forward typing discrepancies among patients (12.3%) and blood donors (29%) was
      ABO subgroups. CONCLUSION: The resolution of ABO typing discrepancy is essential
      to minimise the chance of transfusion of ABO-incompatible blood.

PMID- 29327383
TI  - Large-Scale Noniridescent Structural Color Printing Enabled by Infiltration
      Driven Nonequilibrium Colloidal Assembly.
AB  - Structural colors originating from interaction of light with intricately arranged
      micro-/nanostructures have stimulated considerable interest because of their
      inherent photostability and energy efficiency. In particular, noniridescent
      structural color with wide viewing angle has been receiving increasing attention
      recently. However, no method is yet available for rapid and large-scale
      fabrication of full-spectrum structural color patterns with wide viewing angles.
      Here, infiltration-driven nonequilibrium assembly of colloidal particles on
      liquid-permeable and particle-excluding substrates is demonstrated to direct the
      particles to form amorphous colloidal arrays (ACAs) within milliseconds. The
      infiltration-assisted (IFAST) colloidal assembly opens new possibilities for
      rapid manufacture of noniridescent structural colors of ACAs and straightforward
      structural color mixing. Full-spectrum noniridescent structural colors are
      successfully produced by mixing primary structural colors of red, blue, and
      yellow using a commercial office inkjet printer. Rapid fabrication of large-scale
      structural color patterns with sophisticated color combination/layout by IFAST
      printing is realized. The IFAST technology is versatile for developing structural
      color patterns with wide viewing angles, as colloidal particles, inks, and
      substrates are flexibly designable for diverse applications.

PMID- 29327384
TI  - Children's Acquisition of the English Past-Tense: Evidence for a Single-Route
      Account From Novel Verb Production Data.
AB  - This study adjudicates between two opposing accounts of morphological
      productivity, using English past-tense as its test case. The single-route model
      (e.g., Bybee & Moder, ) posits that both regular and irregular past-tense forms
      are generated by analogy across stored exemplars in associative memory. In
      contrast, the dual-route model (e.g., Prasada & Pinker, ) posits that regular
      inflection requires use of a formal "add -ed" rule that does not require analogy
      across regular past-tense forms. Children (aged 3-4; 5-6; 6-7; 9-10) saw
      animations of an animal performing a novel action described with a novel verb
      (e.g., gezz; chake). Past-tense forms of novel verbs were elicited by prompting
      the child to describe what the animal "did yesterday." Collapsing across age
      group (since no interaction was observed), the likelihood of a verb being
      produced in regular past-tense form (e.g., gezzed; chaked) was positively
      associated with the verb's similarity to existing regular verbs, consistent with
      the single-route model only. Results indicate that children's acquisition of the
      English past-tense is best explained by a single-route analogical mechanism that
      does not incorporate a role for formal rules.

PMID- 29327385
TI  - Ultrathin Semiconductor Superabsorbers from the Visible to the Near-Infrared.
AB  - The design of ultrathin semiconducting materials that achieve broadband
      absorption is a long-sought-after goal of crucial importance for optoelectronic
      applications. To date, attempts to tackle this problem consisted either of the
      use of strong-but narrowband-or broader-but moderate-light-trapping mechanisms.
      Here, a strategy that achieves broadband optimal absorption in arbitrarily thin
      semiconductor materials for all energies above their bandgap is presented. This
      stems from the strong interplay between Brewster modes, sustained by judiciously
      nanostructured thin semiconductors on metal films, and photonic crystal modes.
      Broadband near-unity absorption in Ge ultrathin films is demonstrated, which
      extends from the visible to the Ge bandgap in the near-infrared and is robust
      against angle of incidence variation. The strategy follows an easy and scalable
      fabrication route enabled by soft nanoimprinting lithography, a technique that
      allows seamless integration in many optoelectronic fabrication procedures.

PMID- 29327386
TI  - Self-Healing of a Confined Phase Change Memory Device with a Metallic Surfactant
      Layer.
AB  - Understanding and possibly recovering from the failure mechanisms of phase change
      memories (PCMs) are critical to improving their cycle life. Extensive electrical
      testing and postfailure electron microscopy analysis have shown that stuck-set
      failure can be recovered. Here, self-healing of novel confined PCM devices is
      directly shown by controlling the electromigration of the phase change material
      at the nanoscale. In contrast to the current mushroom PCM, the confined PCM has a
      metallic surfactant layer, which enables effective Joule heating to control the
      phase change material even in the presence of a large void. In situ transmission
      electron microscope movies show that the voltage polarity controls the direction
      of electromigration of the phase change material, which can be used to fill
      nanoscale voids that form during programing. Surprisingly, a single voltage pulse
      can induce dramatic migration of antimony (Sb) due to high current density in the
      PCM device. Based on the finding, self-healing of a large void inside a confined
      PCM device with a metallic liner is demonstrated for the first time.

PMID- 29327388
TI  - Lithiophilic Cu-CuO-Ni Hybrid Structure: Advanced Current Collectors Toward
      Stable Lithium Metal Anodes.
AB  - Metallic lithium (Li) is a promising anode material for next-generation
      rechargeable batteries. However, the dendrite growth of Li and repeated formation
      of solid electrolyte interface during Li plating and stripping result in low
      Coulombic efficiency, internal short circuits, and capacity decay, hampering its
      practical application. In the development of stable Li metal anode, the current
      collector is recognized as a critical component to regulate Li plating. In this
      work, a lithiophilic Cu-CuO-Ni hybrid structure is synthesized as a current
      collector for Li metal anodes. The low overpotential of CuO for Li nucleation and
      the uniform Li+ ion flux induced by the formation of Cu nanowire arrays enable
      effective suppression of the growth of Li dendrites. Moreover, the surface Cu
      layer can act as a protective layer to enhance structural durability of the
      hybrid structure in long-term running. As a result, the Cu-CuO-Ni hybrid
      structure achieves a Coulombic efficiency above 95% for more than 250 cycles at a
      current density of 1 mA cm-2 and 580 h (290 cycles) stable repeated Li plating
      and stripping in a symmetric cell.

PMID- 29327389
TI  - Multivariate analysis of variations in intrinsic foot musculature among
      hominoids.
AB  - Comparative analysis of the foot muscle architecture among extant great apes is
      important for understanding the evolution of the human foot and, hence, human
      habitual bipedal walking. However, to our knowledge, there is no previous report
      of a quantitative comparison of hominoid intrinsic foot muscle dimensions. In the
      present study, we quantitatively compared muscle dimensions of the hominoid foot
      by means of multivariate analysis. The foot muscle mass and physiological cross
      sectional area (PCSA) of five chimpanzees, one bonobo, two gorillas, and six
      orangutans were obtained by our own dissections, and those of humans were taken
      from published accounts. The muscle mass and PCSA were respectively divided by
      the total mass and total PCSA of the intrinsic muscles of the entire foot for
      normalization. Variations in muscle architecture among human and extant great
      apes were quantified based on principal component analysis. Our results
      demonstrated that the muscle architecture of the orangutan was the most
      distinctive, having a larger first dorsal interosseous muscle and smaller
      abductor hallucis brevis muscle. On the other hand, the gorilla was found to be
      unique in having a larger abductor digiti minimi muscle. Humans were
      distinguished from extant great apes by a larger quadratus plantae muscle. The
      chimpanzee and the bonobo appeared to have very similar muscle architecture, with
      an intermediate position between the human and the orangutan. These differences
      (or similarities) in architecture of the intrinsic foot muscles among humans and
      great apes correspond well to the differences in phylogeny, positional behavior,
      and locomotion.

PMID- 29327390
TI  - From Intramolecular (Circular) in an Isolated Molecule to Intermolecular Hole
      Delocalization in a Two-Dimensional Solid-State Assembly: The Case of Pillarene.
AB  - To achieve long-range charge transport/separation and, in turn, bolster the
      efficiency of modern photovoltaic devices, new molecular scaffolds are needed
      that can self-assemble in two-dimensional (2D) arrays while maintaining both
      intra- and intermolecular electronic coupling. In an isolated molecule of
      pillarene, a single hole delocalizes intramolecularly via hopping amongst the
      circularly arrayed hydroquinone ether rings. The crystallization of pillarene
      cation radical produces a 2D self-assembly with three intermolecular dimeric
      (sandwich-like) contacts. Surprisingly, each pillarene in the crystal lattice
      bears a fractional formal charge of +1.5. This unusual stoichiometry of oxidized
      pillarene in crystals arises from effective charge distribution within the 2D
      array via an interplay of intra- and intermolecular electronic couplings. This
      important finding is expected to help advance the rational design of efficient
      solid-state materials for long-range charge transfer.

PMID- 29327387
TI  - Student survey trends in reported alcohol use and influencing factors in
      Australia.
AB  - INTRODUCTION AND AIMS: There is a need to explain reported trends of reduced
      alcohol and drug (substance) use in school-aged children in Australia. This study
      used student survey data collected in the states of Victoria, Western Australia
      and Queensland to examine trends in substance use and associated influencing
      factors. DESIGN AND METHODS: Youth self-reports were examined from 11 cross
      sectional surveys completed by 41 328 adolescents (average age 13.5 years, 52.5%
      female) across 109 Australian communities between 1999 and 2015. Multi-level
      modelling was used to identify trends in adolescent reports of lifetime alcohol,
      tobacco and cannabis use, adjusted for age, gender, social disadvantage and
      minority status. Trends in influencing factors were also examined that included:
      individual attitudes, and family, school and community environments. Multivariate
      analyses estimated the main contributors to alcohol use trends. RESULTS: Alcohol,
      tobacco and cannabis use all fell significantly from 1999 to 2015. Higher levels
      of use were observed in Victoria compared to Western Australia or Queensland.
      Multivariate analyses identified reductions in favourable parent attitudes and
      lower availability of substances as direct contributors to reducing alcohol use
      trends. Indicators of school and family adjustment did not show similar trend
      reductions. DISCUSSION AND CONCLUSIONS: Reductions in adolescent alcohol, tobacco
      and cannabis use from 1999 to 2015 were associated with similar reductions in
      parent favourable attitudes and availability of substances. It is plausible that
      a reduced tendency for parents and other adults to supply adolescent alcohol are
      implicated in the reductions in adolescent alcohol use observed across Australia.

PMID- 29327391
TI  - Molecular phenotype of SLC4A11 missense mutants: Setting the stage for
      personalized medicine in corneal dystrophies.
AB  - SLC4A11 mutations cause cases of congenital hereditary endothelial dystrophy
      (CHED), Harboyan syndrome (HS), and Fuchs endothelial corneal dystrophy (FECD).
      Defective water reabsorption from corneal stroma by corneal endothelial cells
      (CECs) leads to these corneal dystrophies. SLC4A11, in the CEC basolateral
      membrane, facilitates transmembrane movement of H2 O, NH3 , and H+ -equivalents.
      Some SLC4A11 disease mutants have impaired folding, leading to a failure to move
      to the cell surface, which in some cases can be corrected by the drug, glafenine.
      To identify SLC4A11 mutants that are targets for folding-correction therapy, we
      examined 54 SLC4A11 missense mutants. Cell-surface trafficking was assessed on
      immunoblots, by the level of mature, high molecular weight, cell surface
      associated form, and using a bioluminescence resonance energy transfer assay. Low
      level of cell surface trafficking was found in four out of 18 (20%) of FECD
      mutants, 19/ out of 31 (61%) of CHED mutants, and three out of five (60%) of HS
      mutants. Amongst ER-retained mutants, 16 showed increased plasma membrane
      trafficking when grown at 30 degrees C, suggesting that their defect has
      potential for rescue. CHED-causing point mutations mostly resulted in folding
      defects, whereas the majority of FECD missense mutations did not affect
      trafficking, implying functional impairment. We identified mutations that make
      patients candidates for folding correction of their corneal dystrophy.

PMID- 29327392
TI  - Differences in white matter structure and cortical thickness between patients
      with traumatic and idiopathic chronic neck pain: Associations with cognition and
      pain modulation?
AB  - Brain alterations are hypothesized to be present in patients with chronic
      whiplash-associated disorders (CWAD). The aim of this case-control study was to
      examine alterations in cortical thickness and white matter (WM) structure, and
      the presence of brain microhemorrhages in a patient group encountering chronic
      neck pain of traumatic origin (i.e., CWAD) when compared with a patient group
      characterized by nontraumatic chronic neck pain [i.e., chronic idiopathic neck
      pain (CINP)], and healthy controls. Furthermore, we aimed to investigate
      associations between brain structure on one hand and cognitive performance and
      central sensitization (CS) on the other hand. T1-weighted, diffusion-weighted and
      T2*-weighted magnetic resonance images of the brain were acquired in 105 women
      (31 controls, 37 CINP, 37 CWAD) to investigate regional cortical thickness, WM
      structure, and microhemorrhages, respectively. Next, cognitive performance, and
      CS encompassing distant hyperalgesia and conditioned pain modulation (CPM)
      efficacy were examined. Cortical thinning in the left precuneus was revealed in
      CWAD compared with CINP patients. Also, decreased fractional anisotropy, together
      with increased values of mean diffusivity and radial diffusivity could be
      observed in the left cingulum hippocampus and tapetum in CWAD compared with CINP,
      and in the left tapetum in CWAD patients compared with controls. Moreover, the
      extent of WM structural deficits in the left tapetum coincided with decreased CPM
      efficacy in the CWAD group. This yields evidence for associations between
      decreased endogenous pain inhibition, and the degree of regional WM deficits in
      CWAD. Our results emphasize the role of structural brain alterations in women
      with CWAD compared with CINP.

PMID- 29327393
TI  - Pulmonary hypertension in interstitial lung disease: Limitations of
      echocardiography compared to cardiac catheterization.
AB  - BACKGROUND AND OBJECTIVE: In interstitial lung disease (ILD), pulmonary
      hypertension (PH) is a major adverse prognostic determinant. Transthoracic
      echocardiography (TTE) is the most widely used tool when screening for PH,
      although discordance between TTE and right heart catheter (RHC) measured
      pulmonary haemodynamics is increasingly recognized. We evaluated the predictive
      utility of the updated European Society of Cardiology/European Respiratory
      Society (ESC/ERS) TTE screening recommendations against RHC testing in a large,
      well-characterized ILD cohort. METHODS: Two hundred and sixty-five consecutive
      patients with ILD and suspected PH underwent comprehensive assessment, including
      RHC, between 2006 and 2012. ESC/ERS recommended tricuspid regurgitation (TR)
      velocity thresholds for assigning high (>3.4 m/s), intermediate (2.9-3.4 m/s) and
      low (<2.8 m/s) probabilities of PH were evaluated against RHC testing. RESULTS:
      RHC testing confirmed PH in 86% of subjects with a peak TR velocity >3.4 m/s, and
      excluded PH in 60% of ILD subjects with a TR velocity <2.8 m/s. Thus, the ESC/ERS
      guidelines misclassified 40% of subjects as 'low probability' of PH, when PH was
      confirmed on subsequent RHC. Evaluating alternative TR velocity thresholds for
      assigning a low probability of PH did not significantly improve the ability of TR
      velocity to exclude a diagnosis of PH. CONCLUSION: In patients with ILD and
      suspected PH, currently recommended ESC/ERS TR velocity screening thresholds were
      associated with a high positive predictive value (86%) for confirming PH, but
      were of limited value in excluding PH, with 40% of patients misclassified as low
      probability when PH was confirmed at subsequent RHC.

PMID- 29327394
TI  - Photothermal-Responsive Conjugated Polymer Nanoparticles for Remote Control of
      Gene Expression in Living Cells.
AB  - Remote control and noninvasive manipulation of cellular bioprocess has received
      intensive attention as a powerful technology to control cell functions. Here, a
      strategy is developed to remotely control intracellular gene expression with high
      spatial and temporal resolutions by using photothermal-responsive conjugated
      polymer nanoparticles (CPNs) as the transducer under near-infrared light
      irradiation. After being modified with positive charged peptide, the CPNs with
      superior photothermal conversion capacity could effectively coat on the surface
      of living cells and generate localized heat to trigger target gene expression.
      The heat-inducible heat shock protein-70 promoter starts transcription of
      downstream EGFP gene in response to heat shock, thus producing green fluorescent
      protein in the living cells. The combination of heat-inducible gene promoter and
      photothermal-responsive CPNs provides a method for the development of
      thermogenetics.

PMID- 29327395
TI  - Effects of traditional Chinese medicine formula on ruminal fermentation, enzyme
      activities and nutrient digestibility of beef cattle.
AB  - This study was conducted to evaluate effects of traditional Chinese medicine
      formula (TCMF) combined with several herbs on ruminal fermentation, enzyme
      activities and nutrient digestibility. Twenty finishing bulls were assigned to
      control or different TCMFs (Yufeisan-1, -2, -3; 2.5% dry matter (DM) in
      concentrate). Results showed that DM intake was higher (P < 0.05) in the Yufeisan
      3 group than others. Compared to control, apparent digestibility of crude protein
      and neutral detergent fiber were increased (P < 0.05) by Yufeisan-3. No changes
      were observed in ruminal pH, concentrations of ammonia-N, microbial crude protein
      and total volatile fatty acid, whereas ratio of acetate to propionate was lower
      (P < 0.05) and propionate proportion tended to be higher (P < 0.1) in three TCMFs
      than control. Ruminal xylanase (P = 0.061) and carboxymethylcellulase (P < 0.05)
      activities were higher in Yufeisan-3 than control. No changes were observed in
      abundance of total bacteria, fungi and protozoa, whereas Fibrobacter succinogenes
      (P = 0.062) and Ruminococcus flavefaciens (P < 0.05) were increased and total
      methanogens was reduced (P = 0.069) by Yufeisan-3 compared to control. Yufeisan-3
      improved nutrient digestibility and ruminal enzyme activity, and modified
      fermentation and microbial community, maybe due to the presence of Herba
      agastaches, Cortex phellodendri and Gypsum fibrosum.

PMID- 29327396
TI  - Configurational Isomerism in Polyoxovanadates.
AB  - A water-soluble derivative of the polyoxovanadate {V15 E6 O42 } (E=semimetal)
      archetype enables the study of cluster shell rearrangements driven by
      supramolecular interactions. A reaction unique to E=Sb, induced exclusively by
      ligand metathesis in peripheral [Ni(ethylenediamine)3 ]2+ counterions, results in
      the formation of the metastable alpha1 * configurational isomer of the {V14 Sb8
      O42 } cluster type. Contrary to all other polyoxovanadate shell architectures,
      this isomer comprises an inward-oriented vanadyl group and is ca. 50 and 12 kJ
      mol-1 higher in energy than the previously isolated alpha and beta isomers,
      respectively. We discuss this unexpected reaction in light of supramolecular Sb
      O???V and Sb-O???Sb contacts manifested in {V14 Sb8 O42 }2 dimers detected in the
      solid state. ESI MS experiments confirm the stability of these dimers also in
      solution and in the gas phase. DFT calculations indicate that other, as of yet
      elusive isomers of {V14 Sb8 }, might be accessible as well.

PMID- 29327398
TI  - Ways of knowing on the Internet: A qualitative review of cancer websites from a
      critical nursing perspective.
AB  - People diagnosed with cancer typically want information from their doctor or
      nurse. However, many individuals now turn to the Internet to tackle unmet
      information needs and to complement healthcare professional information. The
      purpose of this study was to qualitatively explore the content of commonly
      searched cancer websites from a critical nursing perspective, as this information
      is accessible, and allows patients to address their information needs in ways
      that healthcare professionals cannot. This qualitative examination of websites is
      informed by Carper's fundamental patterns of knowing and complemented with the
      critical view to technology espoused by the philosophy of technology. We
      conducted a review of 20 websites using a two-step interpretive descriptive
      approach and thematic analysis. We identified the dominant discourse to be
      focused on empirical information on treatment, prognosis, and cure, and a paucity
      of sociopolitical, ethical, personal, and esthetic information. In place of
      holistic, nuanced, and accurate knowledge nurses may provide, patients find
      predominantly empirical and biomedical information online. Discussion explores
      and critiques online cancer content, gaps in information, and the importance of
      information diversity. Implications focus on needed discourse around pervasive
      technologies and the nursing role in assessing and directing patients to holistic
      information.

PMID- 29327397
TI  - Translating international HIV treatment guidelines into local priorities in
      Indonesia.
AB  - OBJECTIVE: International guidelines recommend countries to expand antiretroviral
      therapy (ART) to all HIV-infected individuals and establish local-level
      priorities in relation to other treatment, prevention and mitigation
      interventions through fair processes. However, no practical guidance is provided
      for such priority-setting processes. Evidence-informed deliberative processes
      (EDPs) fill this gap and combine stakeholder deliberation to incorporate relevant
      social values with rational decision-making informed by evidence on these values.
      This study reports on the first-time implementation and evaluation of an EDP in
      HIV control, organised to support the AIDS Commission in West Java province,
      Indonesia, in the development of its strategic plan for 2014-2018. METHODS: Under
      the responsibility of the provincial AIDS Commission, an EDP was implemented to
      select priority interventions using six steps: (i) situational analysis; (ii)
      formation of a multistakeholder Consultation Panel; (iii) selection of criteria;
      (iv) identification and assessment of interventions' performance; (v)
      deliberation; and (vi) selection of funding and implementing institutions. An
      independent researcher conducted in-depth interviews (n = 21) with panel members
      to evaluate the process. RESULTS: The Consultation Panel included 23
      stakeholders. They identified 50 interventions and these were evaluated against
      four criteria: impact on the epidemic, stigma reduction, cost-effectiveness and
      universal coverage. After a deliberative discussion, the Consultation Panel
      prioritised a combination of several treatment, prevention and mitigation
      interventions. CONCLUSION: The EDP improved both stakeholder involvement and the
      evidence base for the strategic planning process. EDPs fill an important gap
      which international guidelines and current tools for strategic planning in HIV
      control leave unaddressed.

PMID- 29327399
TI  - Poly(Lactide-Co-Glycolide)-Monomethoxy-Poly-(Polyethylene Glycol) Nanoparticles
      Loaded with Melatonin Protect Adipose-Derived Stem Cells Transplanted in
      Infarcted Heart Tissue.
AB  - Stem cell transplantation is a promising therapeutic strategy for myocardial
      infarction. However, transplanted cells face low survival rates due to oxidative
      stress and the inflammatory microenvironment in ischemic heart tissue. Melatonin
      has been used as a powerful endogenous antioxidant to protect cells from
      oxidative injury. However, melatonin cannot play a long-lasting effect against
      the hostile microenvironment. Nano drug delivery carriers have the ability to
      protect the loaded drug from degradation in physiological environments in a
      controlled manner, which results in longer effects and decreased side effects.
      Therefore, we constructed poly(lactide-co-glycolide)-monomethoxy-poly
      (polyethylene glycol) (PLGA-mPEG) nanoparticles to encapsulate melatonin. We
      tested whether the protective effect of melatonin encapsulated by PLGA-mPEG
      nanoparticles (melatonin nanoparticles [Mel-NPs]) on adipose-derived mesenchymal
      stem cells (ADSCs) was enhanced compared to that of free melatonin both in vitro
      and in vivo. In the in vitro study, we found that Mel-NPs reduced formation of
      the p53- cyclophilin D complex, prevented mitochondrial permeability transition
      pores from opening, and rescued ADSCs from hypoxia/reoxygenation injury.
      Moreover, Mel-NPs can achieve higher ADSC survival rates than free melatonin in
      rat myocardial infarction areas, and the therapeutic effects of ADSCs pretreated
      with Mel-NPs were more apparent. Hence, the combination of Mel-NPs and stem cell
      transplantation may be a promising strategy for myocardial infarction therapy.
      Stem Cells 2018;36:540-550.

PMID- 29327401
TI  - Daclatasvir and reduced-dose sofosbuvir: an effective and pangenotypic treatment
      for hepatitis C in patients with eGFR <30 ml/min.
AB  - BACKGROUND & AIMS: Sofosbuvir is a key agent for HCV treatment. It is not
      recommended for patients with chronic kidney disease (CKD) and estimated
      glomerular filtration rate (eGFR) <30 mL/min. We report real-life experience of
      treating a cohort of CKD patients with eGFR <30 mL/min using daclatasvir and half
      daily dose of sofosbuvir. METHODS: Adults patients who (i) had eGFR<30 ml/min and
      detectable HCV RNA and (ii) were treated with interferon and ribavirin free, DAA
      based regimens were included. All patients were treated with daily doses of
      daclatasvir 60 mg and sofosbuvir 200 mg. The planned duration of treatment was 12
      weeks, except for 24 weeks in those with either clinical evidence of cirrhosis or
      on immunosuppressive drugs. The end-points of the study were: (i) 12 weeks of
      follow-up after treatment completion, (ii) treatment discontinuation, or (iii)
      death or loss to follow-up. RESULTS: Thirty-six (88%) among 41 included patients
      (median [range] age: 48 [19-75] years; 25 [61%] male; genotype 1/3/4 were 17/
      22/2; cirrhosis 5) completed the treatment, two discontinued and three died
      during treatment. On an intention-to-treat basis, HCV RNA were undetectable at 4
      weeks of treatment, treatment completion and after 12 weeks of follow-up in 40/41
      (97.6%), 37/41 (90.2%) and 37/41 (90.2%), respectively. None of the patients had
      a relapse. CONCLUSIONS: Daclatasvir and half-daily dose of sofosbuvir was
      effective against genotype 1 and 3 HCV infection in patients with eGFR <30
      ml/min. This combination was could be a pangenotypic treatment option for such
      patients.

PMID- 29327402
TI  - Response to 'High stoma prevalence and stoma reversal complications following
      anterior resection for rectal cancer: a population-based multicentre study'.

PMID- 29327400
TI  - A vitamin B12 conjugate of exendin-4 improves glucose tolerance without
      associated nausea or hypophagia in rodents.
AB  - AIMS: While pharmacological glucagon-like peptide-1 receptor (GLP-1R) agonists
      are FDA-approved for treating type 2 diabetes mellitus (T2DM) and obesity, a
      major side effect is nausea/malaise. We recently developed a conjugate of vitamin
      B12 (B12) bound to the GLP-1R agonist exendin-4 (Ex4), which displays enhanced
      proteolytic stability and retention of GLP-1R agonism. Here, we evaluate whether
      the conjugate (B12-Ex4) can improve glucose tolerance without producing anorexia
      and malaise. MATERIALS AND METHODS: We evaluated the effects of systemic B12-Ex4
      and unconjugated Ex4 on food intake and body weight change, oral glucose
      tolerance and nausea/malaise in male rats, and on intraperitoneal glucose
      tolerance in mice. To evaluate whether differences in the profile of effects of
      B12-Ex4 vs unconjugated Ex4 are the result of altered CNS penetrance, rats
      received systemic injections of fluorescein-Ex4 (Flex), Cy5-B12 or Cy5-B12-Ex4
      and brain penetrance was evaluated using confocal microscopy. Uptake of
      systemically administered Cy5-B12-Ex4 in insulin-containing pancreatic beta cells
      was also examined. RESULTS: B12-Ex4 conjugate improves glucose tolerance, but
      does not elicit the malaise and anorexia produced by unconjugated Ex4. While Flex
      robustly penetrates into the brain (dorsal vagal complex, paraventricular
      hypothalamus), Cy5-B12 and Cy5-B12-Ex4 fluorescence were not observed centrally,
      supporting an absence of CNS penetrance, in line with observed reduction in CNS
      associated Ex4 side effects. Cy5-B12-Ex4 colocalizes with insulin in the
      pancreas, suggesting direct pancreatic action as a potential mechanism underlying
      the hypoglycaemic effects of B12-Ex4. CONCLUSION: These novel findings highlight
      the potential clinical utility of B12-Ex4 conjugates as possible future T2DM
      therapeutics with reduced incidence of adverse effects.

PMID- 29327404
TI  - A novel red emitting phosphor LiBaB9 O15 :Sm2+ /Sm3+ , li+ with broad excitation
      band for white LEDs.
AB  - A novel tunable red emitting phosphor LiBaB9 O15 :Sm2+ /Sm3+ , Li+ with broad
      excitation band was synthesized by a high temperature solid-state method.
      Luminescence properties were investigated in detail by luminescence, X-ray
      photoelectron spectroscopy (XPS) spectra and CIE chromaticity coordinates. XPS
      data confirmed that there were Sm3+ in LiBaB9 O15 :Sm3+ and Sm2+ /Sm3+ in LiBaB9
      O15 :Sm2+ /Sm3+ , respectively. Spectral property of LiBaB9 O15 :Sm3+ , LiBaB9
      O15 :Sm3+ /Sm2+ and LiBaB9 O15 :Sm2+ , Li+ presented that the excitation band of
      Sm3+ widened and the excitation band of Sm2+ ranged from 350 to 450 nm. And the
      red light color is tunable with changing Li+ concentration. The results indicated
      that LiBaB9 O15 :Sm2+ /Sm3+ , Li+ may be promising red phosphor for white light
      emitting diodes.

PMID- 29327405
TI  - From "Non-encounters" to autonomic agency. Conceptions of patients with low back
      pain about their encounters in the health care system.
AB  - Low back pain is a considerable health problem which affects people around the
      world, causing major healthcare costs. The use of qualitative research methods
      enables us to describe and understand patients' experience of, and attitudes to,
      healthcare. The aim of the present phenomenographic study was to identify and
      describe the contextual nature of the conceptions of patients with low back pain
      of their encounters in the HCS. Seventeen patients with chronic or episodic low
      back pain classified as "high risk" were interviewed in open recall interviews,
      using videos of patients' initial physiotherapy sessions that had been recorded
      previously. The data were analysed using the phenomenographic method. Patients'
      conceptions of their clinical journey were formulated by a variety of themes:
      convincing care, lifestyle change, participation, reciprocality and ethicality of
      encounters. The themes varied in four categories: "non-encounters", seeking
      support, empowering collaboration and autonomic agency. The results showed a
      range of clinical interactions - from very negative and disempowering, to
      empowering and life changing. The key differences between the first and second
      categories were professionals "being present" and patients starting to understand
      their low back pain. Between the second and third category, the key aspects were
      strong therapeutic alliance and the active participation of the patient. Finally,
      the key differences between the third and fourth categories were the patient
      being in charge and taking responsibility while knowing that help was available
      if required. The results may help in improving the care of patients with low back
      pain.

PMID- 29327403
TI  - Biogenesis and regulatory hierarchy of phased small interfering RNAs in plants.
AB  - Several varieties of small RNAs including microRNAs (miRNAs) and small
      interfering RNAs (siRNAs) are generated in plants to regulate development, genome
      stability and response to adverse environments. Phased siRNA (phasiRNA) is a type
      of secondary siRNA that is processed from a miRNA-mediated cleavage of RNA
      transcripts, increasing silencing efficiency or simultaneously suppressing
      multiple target genes. Trans-acting siRNAs (ta-siRNAs) are a particular class of
      phasiRNA produced from noncoding transcripts that silence targets in trans. It
      was originally thought that 'one-hit' and 'two-hit' models were essential for
      processing distinct TAS precursors; however, a single hit event was recently
      shown to be sufficient at triggering all types of ta-siRNAs. This review
      discusses the findings about biogenesis, targeting modes and regulatory networks
      of plant ta-siRNAs. We also summarize recent advances in the generation of other
      phasiRNAs and their possible biological benefits to plants.

PMID- 29327406
TI  - Short and medium-term efficacy of sodium glucose co-transporter-2 (SGLT-2)
      inhibitors: A meta-analysis of randomized clinical trials.
AB  - AIMS: Sodium glucose co-transport-2 (SGLT-2) inhibitors reduce tubular glucose
      reabsorption, producing a reduction of blood glucose without stimulating insulin
      release. The aim of this meta-analysis was the systematic collection of available
      data from randomized trials, in order to establish the durability of the efficacy
      of SGLT-2 inhibitors on glycaemic control and body mass index. METHODS: A meta
      analysis was performed, including all trials with a duration of at least 12
      weeks, comparing SGLT-2 inhibitors with non-SGLT-2 inhibitor agents in type 2
      diabetes. The principal outcome was the effect of SGLT-2 inhibitors on hemoglobin
      A1c (HbA1c) at 12, 24, 52 and 104 weeks. Data on body mass index at the same time
      points were also collected. RESULTS: Among 66 randomized trials, HbA1c reduction
      at 12, 24, 52 and 104 weeks was 0.63% (0.57; 0.68, 0.63% (0.57; 0.70), 0.66%
      (0.57; 0.74) and 0.60% (0.40; 0.81), respectively. SGLT-2 inhibitors showed a
      greater efficacy than dipeptidyl-peptidase-4 inhibitors (DPP-4i). Sulfonylureas
      appeared to be superior to SGLT-2 inhibitors at 12 weeks, but not at 24 and 52
      weeks; SGLT-2 inhibitors produced a greater reduction in HbA1c than did
      sulfonylureas at 104 weeks. SGLT-2 inhibitor-induced weight loss in placebo
      controlled trials appeared to increase progressively with the duration of
      treatment. CONCLUSIONS: SGLT-2 inhibitors showed a good persistence of efficacy,
      at least up to 2 years, with a small but significant superiority over DPP-4i.
      Sulfonylureas are more effective in the very short term, but less effective in
      the longer term.

PMID- 29327407
TI  - Bioavailability and metabolism of rosemary infusion polyphenols using Caco-2 and
      HepG2 cell model systems.
AB  - BACKGROUND: Rosmarinus officinalis is an aromatic plant used in folk medicine as
      a result of the therapeutic properties associated with its phenolic composition,
      being rich in rosmarinic acid (RA) and caffeic acid (CA). To better understand
      the bioactivity of these compounds, their absorption and metabolism were assessed
      in human Caco-2 and HepG2 cells, as small intestine and liver models,
      respectively, using RA and CA standards, as well as a rosemary infusion and
      ferulic acid (FA). RESULTS: Test compounds were partially up-taken and
      metabolized by Caco-2 and HepG2 cells, although a higher metabolization rate was
      observed after hepatic incubation compared to intestinal incubation. CA was the
      compound best absorbed followed by RA and FA, showing metabolites percentages of
      30.4%, 11.8% and 4.4% in Caco-2 and 34.3%, 10.3% and 3.2% in HepG2 cells,
      respectively. RA in the rosemary infusion showed improved bioavailability
      compared to pure RA. Methyl derivatives were the main metabolites detected for CA
      and RA after intestinal and hepatic metabolism, followed by methyl-glucuronidates
      and glucuronidates. RA was also minimally hydrolyzed into CA, whereas FA only was
      glucuronidated. Rosemary polyphenols followed the same biotransformation pathways
      as the standards. In addition, phase II derivatives of luteolin were observed.
      CONCLUSION: Rosemary polyphenols are partially metabolized in both the intestine
      and liver. (c) 2018 Society of Chemical Industry.

PMID- 29327408
TI  - The Photoconversion of Phytochrome Includes an Unproductive Shunt Reaction
      Pathway.
AB  - Phytochromes are modular bimodal photoswitches that control gene expression for
      morphogenetic processes in plants. These functions are triggered by photoinduced
      conversions between the inactive and active states of the photosensory module,
      denoted as Pr and Pfr, respectively. In the present time-resolved resonance Raman
      spectroscopic study of bacterial representatives of this photoreceptor family, we
      demonstrate that these phototransformations do not represent linear processes but
      include a branching reaction back to the initial state, prior to (de)activation
      of the output module. Thus, only a fraction of the photoreceptors undergoing the
      phototransformations can initiate the downstream signaling process, consistent
      with phytochrome's function as a sensor for more durable changes of light
      conditions.

PMID- 29327409
TI  - Cultural aspects of pain: A study of Indian Asian women in the UK.
AB  - OBJECTIVES: Culture and ethnicity are acknowledged as important factors in the
      context of the biopsychosocial model. They may contribute to explaining the
      experience of pain, therapeutic encounters within healthcare, and the strategies
      that individuals use to cope with pain. The present study explored these issues
      in a sample of Indian Asian women in the UK. METHODS: Based on a phenomenological
      approach, 17 women participated in five semi-structured group interviews. Data
      were analysed using qualitative content analysis, so as to identify core themes
      and subthemes inductively from the data. RESULTS: Six themes were identified:
      meaning of pain; personal experience of pain; causes of pain; coping strategies;
      family and friends; experience of healthcare. Pain was conceptualized in both
      physical and mental terms, and its experience was explained largely in terms of
      functional consequences. The causes of pain offered suggested externalized
      beliefs, relating to events in participants' lives, rather than being expressed
      in biomedical terms. Alongside culture-specific therapies, the women spoke of
      coping strategies based on rest and activity. Although satisfaction with
      healthcare appeared to be high overall, problems due to communication - sometimes
      related to a language barrier - were voiced by some participants. CONCLUSIONS:
      Greater attention to cultural aspects of the pain experience may assist health
      professionals in communicating with and managing patients with pain from ethnic
      minority backgrounds.

PMID- 29327411
TI  - Reductive Alkaline Release of N-Glycans Generates a Variety of Unexpected, Useful
      Products.
AB  - Release of O-glycans by reductive beta-elimination has become routine in many
      glyco-analytical laboratories and concomitant release of N-glycans has repeatedly
      been observed. Revisiting this somewhat forgotten mode of N-glycan release
      revealed that all kinds of N-glycans including oligomannosidic and complex-type N
      glycans from plants with 3-linked fucose and from mammals with or without 6
      linked fucose and with sialic acid could be recovered. However, the mass spectra
      of the obtained products revealed very surprising facts. Even after 16 h
      incubation in 1 M sodium borohydride, a large part of the glycans occurred in
      reducing form. Moreover, about one third emerged in the form of the stable amino
      functionalized 1-amino-1-deoxy-glycitol. When avoiding acidic conditions,
      considerable amounts of glycosylamine were observed. In addition, a compound with
      a reduced asparagine and de-N-acetylation products, in particular of sialylated
      glycans, was seen. The relative yields of the products reducing glycosylamine,
      reducing N-glycan, 1-amino-1-deoxy-glycitol or glycitol could be controlled by
      the release conditions, foremost by temperature and borohydride concentration.
      Thus, chemical release of N-glycans constitutes a cost-saving alternative to
      enzymatic hydrolysis for the preparation of precursors for the production of
      reference compounds for various formats of N-glycan analysis. Moreover, it allows
      to obtain a stable amino-functionalized glycan derivative, which can be employed
      to construct glycan arrays or affinity matrices.

PMID- 29327412
TI  - Partial Proteome of the Corynetoxin-Producing Gram-Positive Bacterium,
      Rathayibacter toxicus.
AB  - Rathayibacter toxicus is a Gram-positive bacterium that is the causative agent of
      annual ryegrass toxicity (ARGT), a disease that causes devastating losses in the
      Australian livestock industry. R. toxicus exhibits a complex life cycle, using
      the nematode Anguina funesta as a physical vector to carry it up to the seed head
      of the host plant. ARGT is caused by a tunicamycin-like corynetoxin that is
      produced in R. toxicus-infected seed galls. We analyzed protein expression in R.
      toxicus under stationary growth phase conditions to obtain a more complete
      understanding of the biology of this organism and identify potential targets for
      immunoassay development. A total of 323 unique proteins were identified,
      including those with putative roles in secondary metabolism and pathogenicity.
      The proteome analysis for this complex phytopathogenic Gram-positive bacterium
      will facilitate in the characterization of proteins necessary for host
      colonization and toxin production, and assist in the development of diagnostic
      assays. Data are available via ProteomeXchange with identifier PXD004238.

PMID- 29327413
TI  - ITPA Activity in Children Treated by Azathioprine: Relationship to the Occurrence
      of Adverse Drug Reactions and Inflammatory Response.
AB  - Azathioprine (AZA), a thiopurine drug, is widely used in the treatment of
      children with immunological diseases such as inflammatory bowel disease (IBD) and
      autoimmune hepatitis (AIH); however, interindividual variability in the
      occurrence of adverse drug reactions (ADRs) and drug response is observed. This
      study investigated (i) the relationships between inosine triphosphate
      pyrophosphatase (ITPA) activity, an enzyme involved in thiopurine metabolism, and
      the occurrence of ADRs in children with immunological disease on AZA therapy, and
      (ii) the relationship between ITPA activity and the inflammatory activity
      observed in children with IBD. ITPA and TPMT activities were determined in 106
      children with immunological disease on AZA therapy. Markers of hepatotoxicity,
      myelotoxicity, pancreatitis and inflammation as well as clinical information were
      retrospectively collected during regular medical visits. No significant
      association was found between ITPA activity and hepatotoxicity or clinical ADRs
      such as cutaneous reactions, arthralgia, flulike symptoms and gastrointestinal
      disorders. Concerning myelotoxicity, a significant relation was observed between
      ITPA activity and RBC mean corpuscular volume (MCV; p=0.003). This observation
      may be related to the significant relationship found between high ITPA activity
      and the increase in gamma-globulin level reflecting inflammation (p=0.005). In
      our study, ITPA activity was not associated with occurrence of ADRs, but a
      relationship between high ITPA activity and gamma-globulin, a marker of
      inflammation, was found in children with IBD. Therefore, measurement of ITPA
      activity may help to identify children with IBD predisposed to residual
      inflammation on AZA therapy. Further prospective studies are needed to confirm
      this result.

PMID- 29327410
TI  - Genomic insights into the Acidobacteria reveal strategies for their success in
      terrestrial environments.
AB  - Members of the phylum Acidobacteria are abundant and ubiquitous across soils. We
      performed a large-scale comparative genome analysis spanning subdivisions 1, 3,
      4, 6, 8 and 23 (n = 24) with the goal to identify features to help explain their
      prevalence in soils and understand their ecophysiology. Our analysis revealed
      that bacteriophage integration events along with transposable and mobile elements
      influenced the structure and plasticity of these genomes. Low- and high-affinity
      respiratory oxygen reductases were detected in multiple genomes, suggesting the
      capacity for growing across different oxygen gradients. Among many genomes, the
      capacity to use a diverse collection of carbohydrates, as well as inorganic and
      organic nitrogen sources (such as via extracellular peptidases), was detected -
      both advantageous traits in environments with fluctuating nutrient environments.
      We also identified multiple soil acidobacteria with the potential to scavenge
      atmospheric concentrations of H2 , now encompassing mesophilic soil strains
      within the subdivision 1 and 3, in addition to a previously identified
      thermophilic strain in subdivision 4. This large-scale acidobacteria genome
      analysis reveal traits that provide genomic, physiological and metabolic
      versatility, presumably allowing flexibility and versatility in the challenging
      and fluctuating soil environment.

PMID- 29327414
TI  - E-PREP: A competency-based emergency department procedural training programme.

PMID- 29327415
TI  - Mandatory misrepresentation.
AB  - The ethical use of college membership in the statement of political opinion.

PMID- 29327416
TI  - Comparative Proteomics Studies of Insect Cuticle by Tandem Mass Spectrometry:
      Application of a Novel Proteomics Approach to the Pea Aphid Cuticular Proteins.
AB  - The cuticle is a biological composite material consisting principally of N
      acetylglucosamine polymer embedded in cuticular proteins (CPs). CPs have been
      studied and characterized by mass spectrometry in several cuticular structures
      and in many arthropods. Such analyses were carried out by protein extraction
      using SDS followed by electrophoresis, allowing detection and identification of
      numerous CPs. To build a repertoire of cuticular structures from Bombyx mori,
      Apis mellifera and Anopheles gambiae the use of SDS and electrophoresis was
      avoided. Using the combination of hexafluoroisopropanol and of a surfactant
      compatible with MS, a high number of CPs was identified in An. gambiae wings,
      legs and antennae, and in the thoracic integument cuticle of Ap. mellifera pupae.
      The exoskeleton analysis of B. mori larvae allowed to identify 85 CPs from a
      single larva. Finally, the novel proteomics approach was tested on cuticles left
      behind after the molt from the fourth instar of Acyrthosiphon pisum. Analysis of
      these cast cuticles allowed to identify 100 Ac. pisum CPs as authentic cuticle
      constituents. These correspond to 68% of the total putative CPs previously
      annotated for this pea aphid. While this paper analyzes only the recovered
      cuticular proteins, peptides from many other proteins were also detected.

PMID- 29327417
TI  - Konjac flour noodles associated with gastric outlet obstruction.

PMID- 29327418
TI  - Response to Verbeek and Ruotsalainen letter to the editor.

PMID- 29327420
TI  - Expanding the phenotype of SLC25A42-associated mitochondrial encephalomyopathy.
AB  - SLC25A42 gene encodes an inner mitochondrial membrane protein that imports
      Coenzyme A into the mitochondrial matrix. A mutation in this gene was recently
      reported in a subject born to consanguineous parents who presented with
      mitochondrial myopathy with muscle weakness and lactic acidosis. In this report,
      we present 12 additional individuals with the same founder mutation who presented
      with variable manifestations ranging from asymptomatic lactic acidosis to a
      severe phenotype characterized by developmental regression and epilepsy. Our
      report confirms the link between SLC25A42 and mitochondrial disease in humans,
      and suggests that pathogenic variants in SLC25A42 should be interpreted with the
      understanding that the associated phenotype may be highly variable.

PMID- 29327421
TI  - Ionic liquid chemically bonded basalt fibers for in-tube solid-phase
      microextraction.
AB  - Ionic liquids have been widely used in different fields by advantage of their
      specific properties. In this work, 1-methyl-3-(3-trimethoxysilyl
      propyl)imidazolium chloride was prepared and chemically bonded onto basalt fibers
      for in-tube solid-phase microextraction. Through combining in-tube extraction
      device with high-performance liquid chromatography equipped with a diode array
      detector, an online enrichment and analysis method for eight polycyclic aromatic
      hydrocarbons was established under the optimum conditions. A good enrichment
      factor (52-814), good linearity (0.10-15 and 0.20-15 MUg/L), low limits of
      detection (0.03-0.05 MUg/L), and low limits of quantitation (0.10-0.20 MUg/L)
      were achieved using a sample volume of 50 mL. Analysis method was applied to the
      real samples including the groundwater and wastewater from a chemical industry
      park, some target analytes were detected and the relative recoveries were in the
      range of 80.4-116.8%.

PMID- 29327423
TI  - Corrigendum.

PMID- 29327419
TI  - Treatment interruption in HIV-positive patients followed up in Cameroon's
      antiretroviral treatment programme: individual and health care supply-related
      factors (ANRS-12288 EVOLCam survey).
AB  - INTRODUCTION: Decreasing international financial resources for HIV and increasing
      numbers of antiretroviral treatment (ART)-treated patients may jeopardise
      treatment continuity in low-income settings. Using data from the EVOLCam ANRS
      12288 survey, this study aimed to document the prevalence of unplanned treatment
      interruption for more than 2 consecutive days (TI>2d) and investigate the
      associated individual and health care supply-related factors within the
      Cameroonian ART programme. METHODS: A cross-sectional mixed methods survey was
      carried out between April and December 2014 in 19 HIV services of the Centre and
      Littoral regions. A multilevel logistic model was estimated on 1885 ART-treated
      patients in these services to investigate factors of TI>2d in the past 4 weeks.
      RESULTS: Among the study population, 403 (21%) patients reported TI>2d. Patients
      followed up in hospitals reporting ART stock-outs were more likely to report
      TI>2d while those followed up in the Littoral region, in medium- or small-sized
      hospitals and in HIV services proposing financial support were at lower risk of
      TI>2d. The following individual factors were also associated with a lower risk of
      TI>2d: living in a couple, having children, satisfaction with attention provided
      by doctor, tuberculosis co-infection and not having consulted a traditional
      healer. CONCLUSIONS: Besides identifying individual factors of TI>2d, our study
      highlighted the role of health care supply-related factors in shaping TI in
      Cameroon's ART programme, especially the deleterious effect of ART stock-outs.
      Our results also suggest that the high proportion of patients reporting TI could
      jeopardise progress in the fight against HIV in the country, unless effective
      measures are quickly implemented like ensuring the continuity of ART supply.

PMID- 29327422
TI  - Prognosis and distribution of lymph nodes metastases in resectable primary
      pulmonary lymphoepithelioma-like carcinoma: A large cohort from a single center.
AB  - BACKGROUND: Primary pulmonary lymphoepithelioma-like carcinoma is a rare subtype
      of lung cancer. Until now, the characteristics of lymph nodes metastases in
      resectable cases have not yet been reported. METHODS: In this study, a total of
      87 consecutive patients with primary pulmonary lymphoepithelioma-like carcinoma
      that received surgical treatment were investigated from October 1999 to August
      2016. The clinical and radiological data and follow-up information were extracted
      from hospital records in detail. RESULTS: In a univariate analysis, those
      patients with an early pathological stage (I-II), low rate of lymph node
      metastases (<30%) and a low number of positive lymph nodes (<5) showed longer
      recurrence-free survival and overall survival (all P < 0.05). However, the early
      pathological stage was identified as the only factor independently associated
      with recurrence-free survival by multivariate analysis (P = 0.038). In a
      preoperative lymph nodes evaluation, the accuracy and specificity of computed
      tomography alone were 52.9% (46/87) and 88% (302/343), respectively, and 73.2% of
      these cases with incorrect nodal staging (30/41) were upstaged. Skipping
      metastases were more frequent in operated stage N2 cases (71.4%), whereas whether
      or not those patients showed skipping metastasis did not affect their recurrence
      free survival or overall survival (P > 0.05). The highest metastasis frequencies
      for specific lobes with primary lymphoepithelioma-like carcinoma are as follows:
      #5 left upper lobe (21.4%); #7 left lower lobe (40.7%); #2R (28.6%) and/or #4R
      (14.3%) right upper lobe; #7 (42.9%) right lower lobe; #7 (28%) and/or superior
      mediastinal nodes (36%) right middle lobe. CONCLUSION: Based on accurate staging
      and uncertain survival benefit, complete mediastinal lymph nodes dissection is
      still required for curative resection.

PMID- 29327424
TI  - The Choreography of Group Affiliation.
AB  - When two people move in synchrony, they become more social. Yet it is not clear
      how this effect scales up to larger numbers of people. Does a group need to move
      in unison to affiliate, in what we term unitary synchrony; or does affiliation
      arise from distributed coordination, patterns of coupled movements between
      individual members of a group? We developed choreographic tasks that manipulated
      movement synchrony without explicitly instructing groups to move in unison. Wrist
      accelerometers measured group movement dynamics and we applied cross-recurrence
      analysis to distinguish the temporal features of emergent unitary synchrony
      (simultaneous movement) and distributed coordination (coupled movement).
      Participants' unitary synchrony did not predict pro-social behavior, but their
      distributed coordination predicted how much they liked each other, how they felt
      toward their group, and how much they conformed to each other's opinions. The
      choreography of affiliation arises from distributed coordination of group
      movement dynamics.

PMID- 29327426
TI  - Quantification of total cholesterol in human milk by gas chromatography.
AB  - Human milk provides the key nutrients necessary for infant growth and
      development. The objective of this study was to develop and validate a method to
      analyze the cholesterol content in liquid human milk samples along lactation.
      Direct saponification of the sample using ethanolic potassium hydroxide solution
      under cold conditions was applied and unsaponifiable matter was separated by
      centrifugation. Cholesterol was converted into its trimethylsilyl ether and the
      derivative analyzed by gas chromatography coupled with a flame ionization
      detector. Cholesterol was quantified using epicoprostanol as internal standard.
      The method is suitable for the determination of cholesterol in only 0.3 g of
      human milk. It has been validated showing good repeatability (CV(r) < 15%) and
      intermediate reproducibility (CV(iR) < 15%). The method was used to analyze human
      milk obtained from five mothers collected at day 30(+/-3), 60 (+/-3) and 120 (+/
      3) after delivery. The cholesterol content in human milk slightly decreased from
      13.1 mg/100 g at 1 month to 11.3 mg/100 g 120 days after delivery. The method can
      also be used to determine desmosterol, an intermediate in cholesterol synthesis.

PMID- 29327427
TI  - Aerobic Photooxidative Synthesis of beta-Alkoxy Monohydroperoxides Using an
      Organo Photoredox Catalyst Controlled by a Base.
AB  - Transition-metal-free synthesis of beta-alkoxy monohydroperoxides via aerobic
      photooxidation using an acridinium photocatalyst was developed. This method
      enables the synthesis of some novel hydroperoxides. The peroxide source is
      molecular oxygen, which is cost-effective and atomically efficient. Magnesium
      oxide plays an important role as a base in the catalytic system.

PMID- 29327428
TI  - An endochondral ossification approach to early stage bone repair: Use of tissue
      engineered hypertrophic cartilage constructs as primordial templates for weight
      bearing bone repair.
AB  - Mimicking endochondral ossification to engineer constructs offers a novel
      solution to overcoming the problems associated with poor vascularisation in bone
      repair. This can be achieved by harnessing the angiogenic potency of hypertrophic
      cartilage. In this study, we demonstrate that tissue-engineered hypertrophically
      primed cartilage constructs can be developed from collagen-based scaffolds
      cultured with mesenchymal stem cells. These constructs were subsequently
      implanted into femoral defects in rats. It was evident that the constructs could
      support enhanced early stage healing at 4 weeks of these weight-bearing femoral
      bone defects compared to untreated defects. This study demonstrates the value of
      combining knowledge of development biology and tissue engineering in a
      developmental engineering inspired approach to tissue repair.

PMID- 29327430
TI  - Knowledge, attitudes, representations and declared practices of nurses and
      physicians about obesity in a university hospital: training is essential.
AB  - In the context of a worldwide obesity epidemic, healthcare providers play a key
      role in obesity management. Knowledge of current guidelines and attitudes to
      prevent stigmatization are especially important. This study aimed to assess
      knowledge, attitudes, beliefs, perception of opportunity for intervention,
      declared practices and need for training and material of nurses and physicians
      about obesity in a Swiss University Hospital. A total of 834 physicians and
      nurses filled an online survey. The questionnaire was based on literature,
      exploratory interviews and expert committee review. It was pre-tested with 15
      physicians and nurses. Participants declared a low level of negative attitudes
      towards individuals living with obesity. However, the results highlighted a lack
      of knowledge to diagnose obesity in adults and children, as well as confidence
      and training to care of patients with obesity. One-third of providers did not
      know how to calculate body mass index. Half of providers felt it was part of
      their role to take care of patients with obesity, even if 55% of them had the
      feeling that they did not have adequate training. Nurses and physicians working
      in a university hospital showed a low level of negative attitudes but a lack of
      knowledge and skills on obesity management. Training should be improved in this
      population to insure adequate and coherent messages and equal access to evidence
      based treatment for patients living with obesity.

PMID- 29327429
TI  - In vivo migration of endogenous brain progenitor cells guided by an injectable
      peptide amphiphile biomaterial.
AB  - Biomaterials hold great promise in helping the adult brain regenerate and rebuild
      after trauma. Peptide amphiphiles (PAs) are highly versatile biomaterials,
      gelling and forming macromolecular structures when exposed to physiological
      levels of electrolytes. We are here reporting on the first ever in vivo use of
      self-assembling PA carrying a Tenascin-C signal (E2 Ten-C PA) for the redirection
      of endogenous neuroblasts in the rodent brain. The PA forms highly aligned
      nanofibers, displaying the migratory sequence of Tenascin-C glycoprotein as
      epitope. In this in vivo work, we have formed in situ a gel of aligned PA
      nanofibers presenting a migratory Tenascin-C signal sequence in the ventral horn
      of the rostral migratory stream, creating a track reaching the neocortex. Seven
      days posttransplant, doublecortin positive cells were observed migrating inside
      and alongside the injected biomaterial, reaching the cortex. We observed a 24
      fold increase in number of redirected neuroblasts for the E2 Ten-C PA-injected
      animals compared to control. We also found injecting the E2 Ten-C PA to cause
      minimal neuroinflammatory response. Analysing GFAP+ astrocytes and Iba1+
      microglia activation, the PA does not elicit a stronger neuroinflammatory
      response than would be expected from a small needle stab wound. Redirecting
      endogenous neuroblasts and increasing the number of cells reaching a site of
      injury using PAs may open up new avenues for utilizing the pool of neuroblasts
      and neural stem cells within the adult brain for regenerating damaged brain
      tissue and replacing neurons lost to injury.

PMID- 29327431
TI  - Enhanced bone regeneration and visual monitoring via superparamagnetic iron oxide
      nanoparticle scaffold in rats.
AB  - A main challenge for use of scaffolds in bone engineering involves non-invasive
      monitoring in vivo and enhanced bone regeneration. The tissue repair effect of
      superparamagnetic iron oxide nanoparticles (SPIONs) was demonstrated previously
      by our group. However, testing in vivo is needed to confirm in vitro results.
      Here, SPIONs loaded gelatin sponge (GS) was used as a scaffold (SPIONs-GS) and
      implanted in the incisor sockets of Sprague-Dawley rats. Incisor sockets filled
      with nothing and filled with GS served as controls. Rats were sacrificed at 2 and
      4 weeks. A significant decrease in the signal intensity of T2-weighted magnetic
      resonance imaging (MRI) in the SPIONs-GS group was noted. Changes in image
      intensity of scaffolds (indicating scaffold degradation and interaction with host
      tissues) could be visually monitored over time. Microcomputed tomography showed
      that the SPIONs-GS group had more newly formed bone (64.44 +/- 10.92 vs. 28.1 +/-
      4.49, p < .0001) and a better preserved alveolar ridge than blank control group
      at 4 weeks (0.962 +/- 0.01 vs. 0.92 +/- 0.01, p < .0001). Histology confirmed
      imaging results, showing good consistency in new bone formation and scaffold
      degradation. The number of SPIONs decreased rapidly with time due to quick
      degradation of GS, whereas the number of endocytic SPIONs in cells increased with
      time. These residual SPIONs, together with newly formed bone, could be detected
      by MRI at 4 weeks. Therefore, it was clear that SPIONs induced active
      osteogenesis. In conclusion, good visibility on MRI and enhanced regeneration of
      bone can be obtained by implanting SPIONs-GS in vivo without using an external
      magnetic field.

PMID- 29327432
TI  - A rhodamine-triazole fluorescent chemodosimeter for Cu2+ detection and its
      application in bioimaging.
AB  - A rhodamine-based fluorescent chemodosimeter rhodamine hydrazide-triazole (RHT)
      tethered with a triazole moiety was developed for Cu2+ detection. In aqueous
      medium, the RHT probe exhibited high selectivity and sensitivity toward Cu2+
      among other metal ions. The addition of Cu2+ triggered a fluorescence emission of
      RHT by 384-fold (Phi = 0.33) based on a ring-opening process and a subsequent
      hydrolysis reaction. Moreover, RHT also showed a selective colorimetric response
      toward Cu2+ from colorless solution to pink, readily observed with the naked eye.
      The limit of detection of RHT for Cu2+ was calculated to be 1 nM (0.06 ppb). RHT
      was successfully demonstrated to detect Cu2+ in Chang liver cells by confocal
      fluorescence microscopy.

PMID- 29327433
TI  - Factors influencing skin cancer excision rates in Scottish primary care.
AB  - Skin cancer incidence rates are rising in the UK, yet many areas are experiencing
      a shortage of dermatologists. We sought to compare skin cancer excision rates
      between general practice (GP) surgeons to identify factors associated with good
      practice, through a retrospective analysis of GP skin cancer histopathology
      reports in three Scottish Health Boards over a 4-year period. Postal
      questionnaires were used to explore factors affecting surgeons' excision rates.
      GPs excised 895 skin cancers (4.5% of the 19 853 regional total) during the
      period. Of the basal cell carcinomas, 308 would be classified as low-risk by
      current National Institute for Health and Care Excellence criteria. Of the
      returned questionnaires, 58 accounted for 631 (70.5%) of the excised skin
      cancers. Analysing completeness of skin cancer excision, there was a
      statistically significant difference between GPs performing excision on >= 11
      lesions/month compared with those performing excision on <= 10/month.
      Policymakers may wish to consider systems to facilitate low-risk patients being
      treated by GPs who undertake frequent surgical procedures.

PMID- 29327435
TI  - Impact of dietary induced precocious gut maturation on cecal microbiota and its
      relation to the blood-brain barrier during the postnatal period in rats.
AB  - BACKGROUND: Precocious maturation of the gastrointestinal barrier (GIB) in
      newborn mammals can be induced by dietary provocation, but how this affects the
      gut microbiota and the gut-brain axis remains unknown. The objective of this
      study was to investigate effects of induced GIB maturation on gut microbiota
      composition and blood-brain barrier (BBB) permeability. METHODS: Suckling rats
      were studied at 72 h after gavage with phytohemagglutinin (PHA) or microbial
      protease (PT) to induce maturation of GIB. For comparison, untreated suckling and
      weaned rats were included (n = 10). Human serum albumin (HSA) was administered
      orally and analyzed in blood to assess permeability of the GIB, while
      intraperitoneally injected bovine serum albumin (BSA) was measured in the brain
      tissue for BBB permeability. The cecal microbial composition, plasma
      lipopolysaccharide-binding protein (LBP) levels and short-chain fatty acids in
      serum and brain were analyzed. KEY RESULTS: Cessation of HSA passage to blood
      after PHA or PT treatment was similar to that seen in weaned rats. Interestingly,
      concomitant increases in cecal Bacteroidetes and plasma LBP levels were observed
      after both PHA and PT treatments. The BBB passage of BSA was surprisingly
      elevated after weaning, coinciding with lower plasma LBP levels and specific
      microbial taxa and increased acetate uptake into the brain. CONCLUSIONS &
      INFERENCES: This study provides evidence that the gut microbiota alteration
      following induced precocious GIB maturation may induce low-grade systemic
      inflammation and alter SCFAs utilization in the brain which may also play a
      potential role in GIB-BBB dysfunction disorders in neonates.

PMID- 29327436
TI  - Effect of patterned electrospun hierarchical structures on alignment and
      differentiation of mesenchymal stem cells: Biomimicking bone.
AB  - Considering the complex hierarchical structure of bone, biomimicking the micro
      and nano level features should be an integral part of scaffold fabrication for
      successful bone regeneration. We aim to biomimic the microstructure and
      nanostructure of bone and study the effect of physical cues on cell alignment,
      proliferation, and differentiation. To achieve this, we have divided the
      scaffolds into groups: electrospun SU-8 nanofibers, electrospun SU-8 nanofibers
      with UV treatment, and micropatterned (20 MUm sized ridges and grooves) SU-8
      nanofibers by photolithography with UV treatment. Two types of culture conditions
      were applied: with and without osteoinduction medium. In vitro cell proliferation
      assays, protein estimation, alkaline phosphatase osteodifferentiation assay, live
      dead assay, and cell alignment studies were performed on these micropatterned
      nanofiber domains. Our findings show that patterned surface induced an early
      osteodifferentiation of mesenchymal stem cells even in absence of osteoinduction
      medium. An interesting similarity with the helicoidal plywood model of the bone
      was observed. The cells showed layering and rotation along the patterns with
      time. This resembles the in vivo anisotropic multilamellar bone tissue
      architecture thus, closely mimicking the subcellular features of bone. This might
      serve as a smart biomaterial surface for mesenchymal stem cell differentiation in
      therapeutics where the addition of external chemical factors is a challenge.

PMID- 29327434
TI  - A fast and reliable method for monitoring of prophage-activating chemicals.
AB  - Bacteriophages, that is viruses that infect bacteria, either lyse bacteria
      directly or integrate their genome into the bacterial genome as so-called
      prophages, where they remain at a silent state. Both phages and bacteria are able
      to survive in this state. However, prophages can be reactivated with the
      introduction of chemicals, followed by the release of a high number of phage
      particles, which could infect other bacteria, thus harming ecosystems by a viral
      bloom. The basics for a fast, automatable analytical method for the detection of
      prophage-activating chemicals are developed and successfully tested here. The
      method exploits the differences in metabolic heat produced by Escherichia coli
      with (lambda+) and without the lambda prophages (lambda-). Since the metabolic
      heat primarily reflects opposing effects (i.e. the reduction of heat-producing
      cells by lysis and enhanced heat production to deliver the energetic costs for
      the synthesis of phages), a systematic analysis of the influence of the different
      conditions (experimentally and in silico) was performed and revealed anoxic
      conditions to be best suited. The main advantages of the suggested monitoring
      method are not only the possibility of obtaining fast results (after only few
      hours), but also the option for automation, the low workload (requires only few
      minutes) and the suitability of using commercially available instruments. The
      future challenge following this proof of principle is the development of thermal
      transducers which allow for the electronic subtraction of the lambda+ from the
      lambda- signal.

PMID- 29327437
TI  - Intraspecies variation in a widely distributed tree species regulates the
      responses of soil microbiome to different temperature regimes.
AB  - Plant characteristics in different provenances within a single species may vary
      in response to climate change, which might alter soil microbial communities and
      ecosystem functions. We conducted a glasshouse experiment and grew seedlings of
      three provenances (temperate, subtropical and tropical origins) of a tree species
      (i.e., Eucalyptus tereticornis) at different growth temperatures (18, 21.5, 25,
      28.5, 32 and 35.5 degrees C) for 54 days. At the end of the experiment, bacterial
      and fungal community composition, diversity and abundance were characterized.
      Measured soil functions included surrogates of microbial respiration, enzyme
      activities and nutrient cycling. Using Permutation multivariate analysis of
      variance (PerMANOVA) and network analysis, we found that the identity of tree
      provenances regulated both structure and function of soil microbiomes. In some
      cases, tree provenances substantially affected the response of microbial
      communities to the temperature treatments. For example, we found significant
      interactions of temperature and tree provenance on bacterial community and
      relative abundances of Chloroflexi and Zygomycota, and inorganic nitrogen.
      Microbial abundance was altered in response to increasing temperature, but was
      not affected by tree provenances. Our study provides novel evidence that even a
      small variation in biotic components (i.e., intraspecies tree variation) can
      significantly influence the response of soil microbial community composition and
      specific soil functions to global warming.

PMID- 29327438
TI  - Establishing RNA virus resistance in plants by harnessing CRISPR immune system.
AB  - Recently, CRISPR-Cas (clustered, regularly interspaced short palindromic repeats
      CRISPR-associated proteins) system has been used to produce plants resistant to
      DNA virus infections. However, there is no RNA virus control method in plants
      that uses CRISPR-Cas system to target the viral genome directly. Here, we
      reprogrammed the CRISPR-Cas9 system from Francisella novicida to confer molecular
      immunity against RNA viruses in Nicotiana benthamiana and Arabidopsis plants.
      Plants expressing FnCas9 and sgRNA specific for the cucumber mosaic virus (CMV)
      or tobacco mosaic virus (TMV) exhibited significantly attenuated virus infection
      symptoms and reduced viral RNA accumulation. Furthermore, in the transgenic virus
      targeting plants, the resistance was inheritable and the progenies showed
      significantly less virus accumulation. These data reveal that the CRISPR/Cas9
      system can be used to produce plant that stable resistant to RNA viruses, thereby
      broadening the use of such technology for virus control in agricultural field.

PMID- 29327439
TI  - The "hidden" concealed left-sided accessory pathway: An uncommon cause of SVT in
      young people.
AB  - BACKGROUND: Concealed left-sided accessory pathways (CLAP) are a cause of
      supraventricular tachycardia (SVT) in the young. Most are mapped with right
      ventricular (RV) apical/outflow pacing. Rarely, alternative means of mapping are
      required. We review our experience from three pediatric electrophysiology (EP)
      centers with a rare form of "hidden" CLAP. METHODS: All patients <21 years
      undergoing EP study from 2008 to 2014 with a "hidden" CLAP (defined as an
      accessory pathway [AP] for which RV pacing at cycle lengths [CL] stable for
      mapping did not demonstrate eccentric retrograde conduction) were included.
      EXCLUSION CRITERIA: preexcitation. Demographic, procedural, and follow-up data
      were collected. RESULTS: A total of 23 patients met the criteria (median age,
      14.3 years [range 7-21], weight, 51 kg [31-99]). 21 (96%) had SVT and one AFIB
      (4%). APs were adenosine sensitive in 7/20 patients (35%) and VA conduction was
      decremental in six (26%). CLAP conduction was demonstrable with orthodromic
      reentrant tachycardia in all patients, with RV extrastimulus testing in seven
      (30%) and with rapid RV pacing (<CL 300) in three (13%). Left ventricular (LV)
      pacing demonstrated CLAP conduction in 17/17 (100%) patients in whom it was used.
      All 23 CLAPs were successfully ablated (100%) via transseptal approach with
      radiofrequency energy. Specific ablation techniques included: 16 (70%) during LV
      paced rhythm, four (17%) during orthodromic reciprocating tachycardia (ORT; 3/4
      ventricular entrained), and three (13%) with brief rapid RV pacing. There were no
      complications. At 18 months (range 3-96), there was one recurrence (4%).
      CONCLUSIONS: Some CLAPs are only demonstrable with LV pacing, entrained ORT, or
      rapid RV pacing. LV pacing facilitated preferential AP conduction, allowing for
      mapping while maintaining stable hemodynamics.

PMID- 29327441
TI  - Response to 'Circumferential margin involvement after total mesorectal excision
      for mid or low rectal cancer: are all R1 resections equal?'

PMID- 29327440
TI  - A maize phytochrome-interacting factors protein ZmPIF1 enhances drought tolerance
      by inducing stomatal closure and improves grain yield in Oryza sativa.
AB  - Phytochrome-interacting factors (PIFs) play major roles in regulating plant
      growth and development, but their roles in drought stress remain elusive. Here,
      we cloned and characterized a maize (Zea mays) PIF transcription factor, ZmPIF1.
      The expression level of ZmPIF1 was significantly induced by independent drought
      and abscisic acid (ABA) treatments. The ZmPIF1 transgenic rice and Arabidopsis
      displayed water saving and drought resistance, which were associated with reduced
      a stomatal aperture and transpiration rate. Moreover, the ZmPIF1 transgenic rice
      were hypersensitive to exogenous ABA, while the endogenous ABA level was not
      significantly changed, suggesting that ZmPIF1 was a positive regulator of the ABA
      signalling pathway. Digital gene expression (DGE) results further indicated that
      ZmPIF1 participated in ABA signalling pathway and regulated the stomatal aperture
      in rice. In addition, grain yield and agronomic traits analysis over 4 years
      showed that ZmPIF1 was able to increase the grain yield through an increase in
      tiller and panicle numbers in transgenic rice. Overall, ZmPIF1 plays an important
      role in the ABA-mediated regulation of stomatal closure to control water loss.
      ZmPIF1 can enhance water saving and drought resistance and improve the crop yield
      in rice, illustrating the capacity of ZmPIF1 for crop improvement.

PMID- 29327442
TI  - Transplantation or rurality? Migration and HIV risk among Chinese men who have
      sex with men in the urban areas.
AB  - INTRODUCTION: Migration of men who have sex with men (MSM) from rural to urban
      areas is common across low- and middle-income countries and is widely believed to
      contribute to elevated HIV risk among migrant MSM in urban areas. Little
      consensus exists on whether their risk is due to their transplantation or their
      being from resource-constrained rural areas. This study seeks to clarify the
      relationship between migration and HIV risks by comparing differences in HIV
      related risky sexual behaviours and healthcare utilization across competing
      conceptualizations of migratory statuses. METHODS: In July 2016, MSM >=16 years
      old currently residing in one of eight urban cities in China were recruited for
      an online cross-sectional survey, which collected information on socio
      demographics, sexual behaviours, HIV care-seeking behaviours, and healthcare
      utilization. Based on a question about residency status, each participant was
      classified as an urban local resident, urban transplant, or rural transplant.
      Multivariable multinomial logistic regression was used to examine the
      associations between risky behaviours and healthcare utilization among these
      three groups. RESULTS: Among 2007 MSM, the proportion of local, urban transplant
      and rural transplant were 32% (648/2007), 24% (478/2007), and 44% (881/2007),
      respectively. Compared with urban local resident MSM, urban transplant MSM were
      more likely to have ever tested for HIV (adjusted odds ratio (aOR) = 1.39, 95%
      confidence interval (CI): 1.08 to 1.80). Compared with urban transplant MSM,
      rural transplant MSM were less likely to have utilized any governmental sexual
      health services in the past three months (aOR = 0.75, 95% CI: 0.60 to 0.93), ever
      tested for HIV (aOR = 0.77, 95% CI: 0.61 to 0.96), ever initiated antiretroviral
      therapy (ART) (aOR = 0.16, 95% CI: 0.05 to 0.52), and ever purchased sex (aOR =
      0.57, 95% CI: 0.38 to 0.85). No other significant differences were found in
      sexual behaviours among three groups. CONCLUSIONS: The widely used local/migrant
      categorization obscures important differences in HIV risk present between
      urban/rural subgroups among them. Previous studies of HIV risks in Chinese
      "migrant" may have failed to consider the role of structural factors such as
      discrimination or barriers to healthcare when interpreting their findings of
      higher HIV prevalence in this population. Low ART uptake among rural transplant
      MSM in this study is particularly concerning and underscore the need for HIV
      related interventions tailored for this group.

PMID- 29327443
TI  - Effect of gut stress induced by oxidized wheat gluten on the growth performance,
      gut morphology and oxidative states of broilers.
AB  - This study was to investigate the effect of oxidized wheat gluten (OG) on growth
      performance, gut morphology and its oxidative states of broilers. One hundred and
      eighty-day-old male broilers (10 chicks/pen) were randomly allocated into three
      dietary treatments: control diet (CON), diet with 8% wheat gluten (WG) and diet
      with 8% OG with six pens/treatment. Body weight (BW) (21 and 35 days) and average
      daily gain (ADG) (1-21 days and 22-35 days) decreased (p < .05) and feed
      conversion ratio (FCR) (1-21 days and 22-35 days) increased (p < .05) in OG
      treatment. Feed intake (FI) decreased (p < .05) in WG and OG treatments during 22
      35 days. However, FI was not influenced by dietary treatments during 1-21 days (p
      > .05). The OG-fed broilers had a lower faecal pH value (p < .05) and higher
      faecal moisture content (p < 05) at 14, 21, 28 and 35 days. Villus height, crypt
      depth and V/C value were not different (p > .05) among treatments at 21 and 35
      days. Lipid peroxidation (LPO) (21 and 35 days) and malondialdehyde (MDA) (35
      days) content in crop of OG treatment increased (p < .05). Oxidized glutathione
      (GSSG) (21 days), LPO (21 and 35 days) and MDA (21 and 35 days) content in ileum
      of OG treatment increased (p < .05). The reduced glutathione/oxidized glutathione
      (GSH/GSSG) (21 days) and (GSH) (35 days) in ileum of OG treatment decreased (p <
      .05). The present findings indicate that OG might be a stressor for broiler gut,
      which could induce oxidative stress both in crop and in ileum, and the diarrhoea
      as well. The growth performance of broiler was consequently depressed.

PMID- 29327444
TI  - Developing a flexible, high-efficiency Agrobacterium-mediated sorghum
      transformation system with broad application.
AB  - Sorghum is the fifth most widely planted cereal crop in the world and is commonly
      cultivated in arid and semi-arid regions such as Africa. Despite its importance
      as a food source, sorghum genetic improvement through transgenic approaches has
      been limited because of an inefficient transformation system. Here, we report a
      ternary vector (also known as cohabitating vector) system using a recently
      described pVIR accessory plasmid that facilitates efficient Agrobacterium
      mediated transformation of sorghum. We report regeneration frequencies ranging
      from 6% to 29% in Tx430 using different selectable markers and single copy,
      backbone free 'quality events' ranging from 45% to 66% of the total events
      produced. Furthermore, we successfully applied this ternary system to develop
      transformation protocols for popular but recalcitrant African varieties including
      Macia, Malisor 84-7 and Tegemeo. In addition, we report the use of this
      technology to develop the first stable CRISPR/Cas9-mediated gene knockouts in
      Tx430.

PMID- 29327446
TI  - Current and Military-Specific Gender Minority Stress Factors and Their
      Relationship with Suicide Ideation in Transgender Veterans.
AB  - Research suggests the prevalence of suicide ideation and suicide attempts in the
      transgender veteran community may be upwards of 20 times higher than
      nontransgender veterans, who are known to be at increased risk than the general
      US population. This study aimed to understand the potential influence of external
      and internal minority stress experienced during and after military service on
      past-year and recent suicide ideation in a sample of 201 transgender veterans.
      Nonparametric bootstrapping analyses indicated past-year transgender-specific
      discrimination and rejection (external minority stress) indirectly predicted
      frequency of both past-year and past 2-week suicide ideation through past-year
      shame related to gender identity (internal minority stress). This result was
      significant when controlling for symptoms of depression and demographics. Similar
      patterns emerged when examining relationships among military external and
      internal minority stress on suicide outcomes. These results suggest that attempts
      to reduce both the experience and impact of minority stressors related to gender
      identity during and after military service may be an important avenue for suicide
      prevention.

PMID- 29327445
TI  - Don't just do something, stand there! The value and art of deliberate clinical
      inertia.
AB  - It can be difficult to avoid unnecessary investigations and treatments, which are
      a form of low-value care. Yet every intervention in medicine has potential harms,
      which may outweigh the potential benefits. Deliberate clinical inertia is the art
      of doing nothing as a positive response. This paper provides suggestions on how
      to incorporate deliberate clinical inertia into our daily clinical practice, and
      gives an overview of current initiatives such as 'Choosing Wisely' and the 'Right
      Care Alliance'. The decision to 'do nothing' can be complex due to competing
      factors, and barriers to implementation are highlighted. Several strategies to
      promote deliberate clinical inertia are outlined, with an emphasis on shared
      decision-making. Preventing medical harm must become one of the pillars of modern
      health care and the art of not intervening, that is, deliberate clinical inertia,
      can be a novel patient-centred quality indicator to promote harm reduction.

PMID- 29327447
TI  - iTRAQ-Based Proteomic Analysis Exploring the Influence of Hypoxia on the Proteome
      of Dental Pulp Stem Cells under 3D Culture.
AB  - Hypoxic preconditioning is commonly applied to enhance mesenchymal stem cells
      (MSCs) therapeutic effect before transplantation. Elucidating the effect of
      hypoxic preconditioning would be beneficial for improved application. However,
      the influence of hypoxia on dental tissue derived MSCs cultured in 3D was
      unknown. Thus, the present study is to investigate gene expression and proteome
      of dental pulp stem cells (DPSCs) after hypoxic preconditioning. DPSCs were
      isolated, cultured in a 3D system under the normoxic and hypoxic conditions. The
      gene expression was examined with reverse transcription polymerase chain
      reaction, and the proteome was analyzed using iTRAQ-based mass spectrometry. The
      expressions of HIF-1alpha, VEGFA, KDR at mRNA level was upregulated while BMP-2
      was downregulated. Two thousand one hundred and fifteen proteins were identified
      and 57 proteins exhibited significant differences after hypoxic preconditioning
      (30 up-regulated, 27 down-regulated). Bioinformatic analysis revealed the
      majority of up-regulated proteins are involved in cellular process, angiogenesis,
      protein binding and transport, regulation of response to stimulus, metabolic
      processes, and immune response. Increased IL-6 and decreased TGF-1beta protein
      expression under hypoxic condition were verified by ELISA. Hypoxic
      preconditioning partly affected the gene and protein expression in DPSCs under 3D
      culture and may enhance the efficacy of MSCs transplantation.

PMID- 29327448
TI  - The Saliva Proteome of Dogs: Variations Within and Between Breeds and Between
      Species.
AB  - Saliva is a complex multifunctional fluid that bathes the oral cavity to assist
      in soft and hard tissue maintenance, lubrication, buffering, defense against
      microbes, and initiating digestion of foods. It has been extensively
      characterized in humans but its protein composition in dogs remains poorly
      characterized, yet saliva composition could explain (patho) physiological
      differences between individuals, breeds and with humans. This pilot discovery
      study aimed to characterize canine saliva from two breeds, Labrador retrievers
      and Beagles, and to compare this with human saliva using quantitative mass
      spectrometry. The analysis demonstrated considerable inter-individual variation
      and difference between breeds; however these were small in comparison to the
      differences between species. Functional mapping suggested roles of detected
      proteins similar to those found in human saliva with the exception of the
      initiation of digestion as salivary amylase was lacking or at very low abundance
      in canine saliva samples. Many potential anti-microbial proteins were detected
      agreeing with the notion that the oral cavity is under continuous microbial
      challenge.

PMID- 29327449
TI  - Clinical, microbiological and cytomorphometric evaluation of low-level laser
      therapy as an adjunct to periodontal therapy in patients with chronic
      periodontitis.
AB  - OBJECTIVE: A clinical prospective study was designed to evaluate microbiological,
      cytomorphometric and clinical efficacy of low-level laser therapy (LLLT) as an
      adjunct to periodontal therapy in the treatment of chronic periodontitis.
      METHODS: Sixty subjects were included and randomly assigned into 2 groups: SRP
      (scaling root planning) group (n = 30) and LLLT + SRP group (n = 30). Clinical
      parameters were measured before intervention, after the fifth treatment, and
      after a month. All subjects received oral hygiene instructions and full-mouth
      conservative periodontal treatment (removal of dental plaque followed by SRP).
      Afterwards, in group II, Kavo LLLT (980 nm, 0.2 W, 6 J/cm2 ) was applied.
      Subgingival samples were collected at baseline and after the fifth treatment to
      quantify Aggregatibacter actinomycetemcomitans, Prevotella intermedia,
      Porphyromonas gingivalis, Tannerella forsythensis and Treponema denticola by
      polymerase chain reaction (PCR). Gingival swabs were taken, and direct smears
      were prepared on slides for cytomorphometric analysis. RESULTS: Evaluation using
      clinical parameters showed better results in LLLT group. A statistically
      significant decrease in the prevalence of bacteria after treatment in LLLT group
      was observed for the following: T. forsythensis and T. denticola (P < .001), P.
      gingivalis (P < .01), A. actinomycetemcomitans and P. intermedia (P < .05). The
      values of nuclear area, perimeter and Ferret's diameter were significantly lower
      in both studied groups after treatment, but statistical significance was higher
      in LLLT group (P < .001) than in the SRP therapy group (P < .05). CONCLUSION: Low
      level laser therapy as an adjunct to periodontal therapy demonstrates short-term
      additional bacteriological, cytological and clinical benefits.

PMID- 29327450
TI  - The black legend on the Spanish presence in the low countries: Verifying shared
      beliefs on genetic ancestry.
AB  - OBJECTIVES: War atrocities committed by the Spanish army in the Low Countries
      during the 16th century are so ingrained in the collective memory of Belgian and
      Dutch societies that they generally assume a signature of this history to be
      present in their genetic ancestry. Historians claim this assumption is a
      consequence of the so-called "Black Legend" and negative propaganda portraying
      and remembering Spanish soldiers as extreme sexual aggressors. The impact of the
      presence of Spaniards during the Dutch Revolt on the genetic variation in the Low
      Countries has been verified in this study. MATERIALS AND METHODS: A recent
      population genetic analysis of Iberian-associated Y-chromosomal variation among
      Europe is enlarged with representative samples of Dutch (N = 250) and Flemish (N
      = 1,087) males. Frequencies of these variants are also compared between donors
      whose oldest reported paternal ancestors lived in-nowadays Flemish-cities
      affected by so-called Spanish Furies (N = 116) versus other patrilineages in
      current Flemish territory (N = 971). RESULTS: The frequencies of Y-chromosomal
      markers Z195 and SRY2627 decline steeply going north from Spain and the data for
      the Flemish and Dutch populations fits within this pattern. No trend of higher
      frequencies of these variants has been found within the well-ascertained samples
      associated with Spanish Fury cities. DISCUSSION: Although sexual aggression did
      occur in the 16th century, these activities did not leave a traceable "Spanish"
      genetic signature in the autochthonous genome of the Low Countries. Our results
      support the view that the 'Black Legend' and historical propaganda on sexual
      aggression have nurtured today's incorrect assumptions regarding genetic
      ancestry.

PMID- 29327451
TI  - Strengthening standards, transparency, and collaboration to support medicine
      evaluation: Ten years of the European Network of Centres for Pharmacoepidemiology
      and Pharmacovigilance (ENCePP).

PMID- 29327453
TI  - Catalytic Asymmetric Dearomatization of Indolyl Dihydropyridines through an
      Enamine Isomerization/Spirocyclization/Transfer Hydrogenation Sequence.
AB  - A highly efficient synthesis of enantioenriched spiroindolines by catalytic
      asymmetric dearomatization of indolyl dihydropyridines through a chiral
      phosphoric acid catalyzed enamine isomerization/spirocyclization/transfer
      hydrogenation sequence has been developed. This reaction proceeds under mild
      reaction conditions, affording novel spiroindolines in good yields (up to 88 %)
      with excellent enantioselectivity (up to 97 % ee). DFT calculations provide
      insights into the reaction mechanism as well as the origin of stereochemistry.

PMID- 29327452
TI  - Regenerative effects of human embryonic stem cell-derived neural crest cells for
      treatment of peripheral nerve injury.
AB  - Surgical intervention is the current gold standard treatment following peripheral
      nerve injury. However, this approach has limitations, and full recovery of both
      motor and sensory modalities often remains incomplete. The development of
      artificial nerve grafts that either complement or replace current surgical
      procedures is therefore of paramount importance. An essential component of
      artificial grafts is biodegradable conduits and transplanted cells that provide
      trophic support during the regenerative process. Neural crest cells are promising
      support cell candidates because they are the parent population to many peripheral
      nervous system lineages. In this study, neural crest cells were differentiated
      from human embryonic stem cells. The differentiated cells exhibited typical
      stellate morphology and protein expression signatures that were comparable with
      native neural crest. Conditioned media harvested from the differentiated cells
      contained a range of biologically active trophic factors and was able to
      stimulate in vitro neurite outgrowth. Differentiated neural crest cells were
      seeded into a biodegradable nerve conduit, and their regeneration potential was
      assessed in a rat sciatic nerve injury model. A robust regeneration front was
      observed across the entire width of the conduit seeded with the differentiated
      neural crest cells. Moreover, the up-regulation of several regeneration-related
      genes was observed within the dorsal root ganglion and spinal cord segments
      harvested from transplanted animals. Our results demonstrate that the
      differentiated neural crest cells are biologically active and provide trophic
      support to stimulate peripheral nerve regeneration. Differentiated neural crest
      cells are therefore promising supporting cell candidates to aid in peripheral
      nerve repair.

PMID- 29327454
TI  - Ultrafast All-Optical Switching of Germanium-Based Flexible Metaphotonic Devices.
AB  - Incorporating semiconductors as active media into metamaterials offers
      opportunities for a wide range of dynamically switchable/tunable, technologically
      relevant optical functionalities enabled by strong, resonant light-matter
      interactions within the semiconductor. Here, a germanium-thin-film-based flexible
      metaphotonic device for ultrafast optical switching of terahertz radiation is
      experimentally demonstrated. A resonant transmission modulation depth of 90% is
      achieved, with an ultrafast full recovery time of 17 ps. An observed sub
      picosecond decay constant of 670 fs is attributed to the presence of trap
      assisted recombination sites in the thermally evaporated germanium film.

PMID- 29327455
TI  - Bioactivity guided fractionation of methanolic extract of Terminalia arjuna for
      its CYP3A and CYP2D inhibition in rat liver microsomes.
AB  - Terminalia arjuna (T. arjuna) is an Indian medicinal plant belonging to the
      family Combretaceae and possesses numerous therapeutic activities including its
      immense cardioprotective activity. In the present work, a methanolic bark extract
      of T. arjuna was evaluated for CYP3A and CYP2D inhibition potential in rat liver
      microsomes (RLM). Further, the methanolic bark extract was fractionated
      successively using increasing polarity solvents starting with petroleum ether,
      chloroform, ethyl acetate and n-butanol. The fractions so obtained were also
      evaluated for their CYP3A and CYP2D inhibition potential. Probe substrates
      testosterone and dextromethorphan were used for CYP3A and CYP2D respectively. The
      IC50 values for the methanolic extract and the fractions were found to be less
      than 50 MUg/ml in RLM for both CYP3A and CYP2D isoenzymes. The most potent n
      butanol fraction was further fractionated with column chromatography to isolate
      the highest active constituent responsible for the activity. Fraction 4 of the n
      butanol extract was the most potent fraction with IC50 values of 5.64 +/- 0.735
      MUg/ml and 16.63 +/- 0.879 MUg/ml for CYP3A and CYP2D in RLM, respectively.
      Therefore, in vitro data indicated that the Terminalia arjuna extract contains
      constituents that can potentially inhibit the CYP3A and CYP2D isoenzymes which
      may in turn lead to pharmacokinetic drug-herb interaction.

PMID- 29327457
TI  - Solvatochromic study of 3-N-(N'-methylacetamidino)benzanthrone and its
      interaction with dopamine by the fluorescence quenching mechanism.
AB  - The change in photophysical properties of the organic molecule due to
      solvatochromic effect caused by different solvent environments at room
      temperature gives information about the dipole moments of 3-N-(N'
      methylacetamidino)benzanthrone (3-MAB). The quantum yield, fluorescence lifetime
      of 3-MAB was measured in different solvents to calculate radiative and non
      radiative rate constants. The results revealed that the excited state dipole
      moment (MUe ) is relatively larger compared to the ground state dipole moment
      (MUg ), indicating the excited state of the dye under study is more polar than
      the ground state and the same trend is noticed with theoretical calculations
      performed using the CAM-B3LYP/6-311+G(d,p) method. Further, the study on
      preferential solvation was carried out for 3-MAB dye in ethyl acetate-methanol
      solvent mixture. The fluorescence quenching method has been employed for the
      detection of dopamine using 3-MAB as fluorescent probe, using steady-state and
      time resolved methods at room temperature. The method enables dopamine in the
      micro molar range to be detected. Also, an attempt to verify the quenching
      process by employing different models has been tried. Various rate parameters are
      measured using these models, our results indicates the quenching process is
      diffusion limited.

PMID- 29327458
TI  - Lead-induced DNA damage and cell apoptosis in human renal proximal tubular
      epithelial cell: Attenuation via N-acetyl cysteine and tannic acid.
AB  - This study investigates the exposure of lead-induced reactive oxygen species
      (ROS) generation, DNA damage, and apoptosis and also evaluates the therapeutic
      intervention using antioxidants in human renal proximal tubular cells (HK-2
      cells). Following treatment of HK-2 cells with an increasing concentration of
      lead nitrate (0-50 MUM) for 24 h, the intracellular ROS level increased whereas
      the GSH level decreased significantly in a dose-dependent manner. Comet assay
      results revealed that lead nitrate showed the ability to increase the levels of
      DNA strand breaks in HK-2 cells. Lead exposure also induced apoptosis through
      caspase-3 activation at 30 MUg/mL. Pretreatment with N-acetylcysteine (NAC) and
      tannic acid showed a significant ameliorating effect on lead-induced ROS, DNA
      damage, and apoptosis. In conclusion, lead induces ROS, which may exacerbate the
      DNA damage and apoptosis via caspase-3 activation. Additionally, supplementation
      of antioxidants such as NAC and tannic acid may be used as salvage therapy for
      lead-induced DNA damage and apoptosis in an exposed person.

PMID- 29327456
TI  - Discovery and Characterization of CD12681, a Potent RORgamma Inverse Agonist,
      Preclinical Candidate for the Topical Treatment of Psoriasis.
AB  - With possible implications in multiple autoimmune diseases, the retinoic acid
      receptor-related orphan receptor RORgamma has become a sought-after target in the
      pharmaceutical industry. Herein are described the efforts to identify a potent
      RORgamma inverse agonist compatible with topical application for the treatment of
      skin diseases. These efforts culminated in the discovery of N-(2,4
      dimethylphenyl)-N-isobutyl-2-oxo-1-[(tetrahydro-2H-pyran-4-yl)methyl]-2,3-dihydro
      1H-benzo[d]imidazole-5-sulfonamide (CD12681), a potent inverse agonist with in
      vivo activity in an IL-23-induced mouse skin inflammation model.

PMID- 29327459
TI  - Subacute cutaneous lupus erythematosus: is clopidogrel a trigger?

PMID- 29327460
TI  - Nanocrystal-Polymer Particles: Extended Delivery Carriers for Osteoarthritis
      Treatment.
AB  - An efficient treatment for osteoarthritis (OA) can benefit from the local release
      of a high therapeutic dose over an extended period of time. Such a treatment will
      minimize systemic side effects and avoid the inconvenience of frequent
      injections. To this aim, nanocrystal-polymer particles (NPPs) are developed by
      combining the advantages of nanotechnology and microparticles. Nanocrystals are
      produced by wet milling kartogenin (KGN), which is known to promote
      chondrogenesis and to foster chondroprotection. A fluorescent biodegradable
      polymer is synthesized for intravital particle tracking. Polymer microparticles
      with 320 nm embedded KGN nanocrystals (KGN-NPPs) show a high drug loading of
      31.5% (w/w) and an extended drug release of 62% over 3 months. In vitro, these
      particles do not alter mitochondrial activity in cultured human OA synoviocytes.
      In vivo, KGN-NPPs demonstrate higher bioactivity than a KGN solution in a murine
      mechanistic OA model based on histological assessment (Osteoarthritis Research
      Society International score), epiphyseal thickness (microcomputed tomography), OA
      biomarkers (e.g., vascular endothelial growth factor, Adamts5), and prolonged
      intra-articular persistence (fluorescence analysis). This work provides proof-of
      concept of a novel and innovative extended drug delivery system with the
      potential to treat human OA.

PMID- 29327462
TI  - Propensity score-matched outcomes after thoracic epidural or paravertebral
      analgesia for thoracotomy.
AB  - It is not known which regional analgesic technique is most effective or safest
      after open lung resection. We retrospectively examined outcomes in 828 patients
      who received thoracic epidural analgesia and 791 patients who received
      paravertebral block after lung resection between 2008 and 2012. We analysed
      outcomes for 648 patients, 324 who had each analgesic technique, matched by
      propensity scores generated with peri-operative data. There were 22 out of 324
      (7%) postoperative respiratory complications after thoracic epidural and 23 out
      of 324 (7%) after paravertebral block, p = 0.88. For any postoperative
      complication, there were 80 out of 324 (25%) and 78 out of 324 (24%)
      complications, respectively, p = 0.85. There were 17 out of 324 (5%) re
      admissions to intensive care after thoracic epidural and 17 out of 324 (5%) after
      paravertebral block, p > 0.99, and the number of deaths before discharge were 6
      out of 324 (2%) and 4 out of 324 (1%), respectively, p = 0.53. There was no
      significant difference in median (IQR [range]) hospital stay after thoracic
      epidural or paravertebral block, 6 (5-9 [2-94]) days vs. 6 (5-9 [2-122]),
      respectively, p = 0.83. Our study suggests that rates of complications as well as
      length of hospital stay after thoracic epidural analgesia and paravertebral
      blockade are similar. We were unable to compare analgesic efficacy due to
      incomplete data.

PMID- 29327461
TI  - Well-Balanced Ambipolar Conjugated Polymers Featuring Mild Glass Transition
      Temperatures Toward High-Performance Flexible Field-Effect Transistors.
AB  - Conjugated polymers, which can be fabricated by simple processing techniques and
      possess excellent electrical performance, are key to the fabrication of flexible
      polymer field-effect transistors (PFETs) and integrated circuits. Herein, two
      ambipolar conjugated polymers based on (3E,7E)-3,7-bis(2-oxo-1H-pyrrolo[2,3
      b]pyridin-3(2H)-ylidene)benzo[1,2-b:4,5-b']difuran-2,6(3H,7H)-dione and
      dithienylbenzothiadiazole units, namely PNBDOPV-DTBT and PNBDOPV-DTF2BT, are
      developed. Both copolymers possess almost planar conjugated backbone
      conformations and suitable highest occupied molecular orbital (HOMO)/lowest
      unoccupied molecular orbital (LUMO) energy levels (-5.64/-4.38 eV for PNBDOPV
      DTBT and -5.79/-4.48 eV for PNBDOPV-DTF2BT). Note that PNBDOPV-DTBT has a glass
      transition temperature (140  degrees C) lower than the deformation temperature of
      polyethylene terephthalate (PET), meaning well-ordered molecular packing can be
      obtained on PET substrate before its deformation in mild thermal annealing
      process. Flexible PFETs based on PNBDOPV-DTBT fabricated on PET substrates
      exhibit high and well-balanced hole/electron mobilities of 4.68/4.72 cm2 V-1 s-1
      under ambient conditions. After the further modification of Au source/drain
      electrodes with 1-octanethiol self-assembled monolayers, impressively high and
      well-balanced hole/electron mobilities up to 5.97/7.07 cm2 V-1 s-1 are achieved
      in the flexible PFETs. Meanwhile, flexible complementary-like inverters based on
      PNBDOPV-DTBT on PET substrate also afford a much high gain of 148. The device
      performances of both the PFETs and inverters are among the highest values for
      ambipolar conjugated polymers reported to date.

PMID- 29327463
TI  - Subcutaneous implantable cardioverter defibrillator (S-ICD) shocks in a patient
      with a left ventricular assist device.

PMID- 29327465
TI  - Has analgesia changed for lung resection surgery?

PMID- 29327464
TI  - The expression of an exogenous ACC deaminase by the endophyte Serratia grimesii
      BXF1 promotes the early nodulation and growth of common bean.
AB  - : Ethylene acts as an inhibitor of the nodulation process of leguminous plants.
      However, some bacteria can decrease deleterious ethylene levels by the action of
      the enzyme 1-aminocyclopropane-1-carboxylate (ACC) deaminase which degrades ACC,
      the ethylene precursor in all higher plants. Co-inoculation of rhizobia with
      endophytes enhances the rhizobial symbiotic efficiency with legumes, improving
      both nodulation and nitrogen fixation. However, not much is understood about the
      mechanisms employed by these endophytic bacteria. In this regard, the role of ACC
      deaminase from endophytic strains in assisting rhizobia in this process has yet
      to be confirmed. In this study, the role of ACC deaminase in an endophyte's
      ability to increase Rhizobium tropici nodulation of common bean was evaluated. To
      assess the effect of ACC deaminase in an endophyte's ability to promote rhizobial
      nodulation, the endophyte Serratia grimesii BXF1, which does not encode ACC
      deaminase, was transformed with an exogenous acdS gene. The results obtained
      indicate that the ACC deaminase-overexpressing transformant strain increased
      common bean growth, and enhanced the nodulation abilities of R. tropici CIAT899,
      in both cases compared to the wild-type non-transformed strain. Furthermore,
      plant inoculation with the ACC deaminase-overproducing strain led to an increased
      level of plant protection against a seed-borne pathogen. SIGNIFICANCE AND IMPACT
      OF THE STUDY: In this work, we studied the effect of ACC deaminase production by
      the bacterial endophyte Serratia grimesi BXF1, and its impact on the nodulation
      process of common bean. The results obtained indicate that ACC deaminase is an
      asset to the synergetic interaction between rhizobia and the endophyte,
      positively contributing to the overall legume-rhizobia symbiosis by regulating
      inhibitory ethylene levels that might otherwise inhibit nodulation and overall
      plant growth. The use of rhizobia together with an ACC deaminase-producing
      endophyte is, therefore, an important strategy for the development of new
      bacterial inoculants with increased performance.

PMID- 29327466
TI  - Analysis of trace levels of impurities and hydrogen isotopes in helium purge gas
      using gas chromatography for tritium extraction system of an Indian lead lithium
      ceramic breeder test blanket module.
AB  - In the fusion fuel cycle, the accurate analysis and understanding of the chemical
      composition of any gas mixture is of great importance for the efficient design of
      a tritium extraction and purification system or any tritium handling system.
      Methods like laser Raman spectroscopy and gas chromatography with thermal
      conductivity detector have been considered for hydrogen isotopes analyses in fuel
      cycles. Gas chromatography with a cryogenic separation column has been used for
      the analysis of hydrogen isotopes gas mixtures in general due to its high
      reliability and ease of operation. Hydrogen isotopes gas mixture analysis with
      cryogenic columns has been reported earlier using different column materials for
      percentage level composition. In the present work, trace levels of hydrogen
      isotopes (~100 ppm of H2 and D2 ) have been analyzed with a Zeolite 5A and a
      modified gamma-Al2 O3 column. Impurities in He gas (~10 ppm of H2 , O2 , and N2 )
      have been analyzed using a Zeolite 13-X column. Gas chromatography with discharge
      ionization detection has been utilized for this purpose. The results of these
      experiments suggest that the columns developed were able to separate ppm levels
      of the desired components with a small response time (<6 min) and good resolution
      in both cases.

PMID- 29327468
TI  - Why do people become health workers? Analysis from life histories in 4 post
      conflict and post-crisis countries.
AB  - While there is a growing body of literature on how to attract and retain health
      workers once they are trained, there is much less published on what motivates
      people to train as health professions in the first place in low- and middle
      income countries and what difference this makes to later retention. In this
      article, we examine patterns in expressed motivation to join the profession
      across different cadres, based on 103 life history interviews conducted in
      northern Uganda, Sierra Leone, Cambodia, and Zimbabwe. A rich mix of reported
      motivations for joining the profession was revealed, including strong influence
      of "personal calling," exhortations of family and friends, early experiences, and
      chance factors. Desire for social status and high respect for health
      professionals were also significant. Economic factors are also important-not just
      perceptions of future salaries and job security but also more immediate ones,
      such as low cost or free training. These allowed low-income participants to
      access the health professions, to which they had shown considerably loyalty. The
      lessons learned from these cohorts, which had remained in service through periods
      of conflict and crisis, can influence recruitment and training policies in
      similar contexts to ensure a resilient health workforce.

PMID- 29327467
TI  - ERBB3-Binding Protein 1 (EBP1) Is a Novel Developmental Pluripotency-Associated-4
      (DPPA4) Cofactor in Human Pluripotent Cells.
AB  - Developmental Pluripotency-Associated-4 (DPPA4) is one of the few core
      pluripotency genes lacking clearly defined molecular and cellular functions.
      Here, we used a proteomics screening approach of human embryonic stem cell (hESC)
      nuclear extract to determine DPPA4 molecular functions through identification of
      novel cofactors. Unexpectedly, the signaling molecule ERBB3-binding protein 1
      (EBP1) was the strongest candidate binding partner for DPPA4 in hESC. EBP1 is a
      growth factor signaling mediator present in two isoforms, p48 and p42. The two
      isoforms generally have opposing functions, however their roles in pluripotent
      cells have not been established. We found that DPPA4 preferentially binds p48 in
      pluripotent and NTERA-2 cells, but this interaction is largely absent in non
      pluripotent cells and is reduced with differentiation. The DPPA4-EBP1 interaction
      is mediated at least in part in DPPA4 by the highly conserved SAF-A/B, Acinus and
      PIAS (SAP) domain. Functionally, we found that DPPA4 transcriptional repressive
      function in reporter assays is significantly increased by specific p48 knockdown,
      an effect that was abolished with an interaction-deficient DPPA4 DeltaSAP mutant.
      Thus, DPPA4 and EBP1 may cooperate in transcriptional functions through their
      physical association in a pluripotent cell specific context. Our study identifies
      EBP1 as a novel pluripotency cofactor and provides insight into potential
      mechanisms used by DPPA4 in regulating pluripotency through its association with
      EBP1. Stem Cells 2018;36:671-682.

PMID- 29327469
TI  - A retrospective survey of exposure history to chemotherapy or radiotherapy in 940
      consecutive patients with primary myelofibrosis.

PMID- 29327470
TI  - Investigation of the effect of rapid and slow external pH increases on
      Enterococcus faecalis biofilm grown on dentine.
AB  - BACKGROUND: Calcium hydroxide is a common endodontic medicament and has an
      antimicrobial effect by increasing the localized pH within the root canal.
      However, Enterococcus faecalis has shown some resistance to calcium hydroxide.
      METHODS: A flow cell apparatus was used to grow an E. faecalis biofilm on dentine
      discs. Following 4 weeks growth in Todd Hewitt Broth, flow cells were exposed to
      either a rapid or slow increase to pH 11.5 or 12.5. Cellular viability was
      determined using serial plating and the number of colony-forming units was
      normalized against the cellular protein content. Scanning electron microscopy was
      carried out to qualitatively observe the effects of the different rates of pH
      increase. RESULTS: A significant difference in viability between the pH rapid and
      slow groups was not shown in this study. Compared with pH 11.5 solutions, pH 12.5
      solutions were more effective at killing bacteria although some E. faecalis still
      survived. CONCLUSIONS: Enterococcus faecalis did not adapt and develop a greater
      resistance to high pH following a slow rise in pH compared with a rapid rise in
      pH. As expected, pH 12.5 was more effective in reducing bacterial numbers
      compared with pH 11.5 although E. faecalis was not completely eliminated.

PMID- 29327471
TI  - Exploring microbial N2 O reduction: a continuous enrichment in nitrogen free
      medium.
AB  - N2 O is a potent greenhouse gas, but also a potent electron acceptor. In search
      of thermodynamically favourable - yet undescribed - metabolic pathways involving
      N2 O reduction, we set up a continuous microbial enrichment, inoculated with
      activated sludge, fed with N2 O as the sole electron acceptor and acetate as an
      electron donor. A nitrogen-free mineral medium was used with the intention of
      creating a selective pressure towards organisms that would use N2 O directly as
      source of nitrogen for cell synthesis. Instead, we obtained a culture dominated
      by microorganisms of the Rhodocyclaceae family growing by N2 O reduction to N2
      coupled to N2 fixation. Biomass yields of this culture were 40% lower than those
      of a previously reported culture grown under comparable conditions but with an
      NH4+-amended medium, as expected from the extra energy expense of N2 fixation.
      Interestingly, we found no significant difference in yields whether N2 O or
      acetate was the growth-limiting substrate in the chemostat in contrast to the
      study with NH4+-amended medium, in which biomass yields were roughly 30% lower
      during acetate limiting conditions.

PMID- 29327473
TI  - Risk assessment for metalworking fluids and cancer outcomes.
AB  - BACKGROUND: Metalworking fluids (MWF) are complex mixtures with dermal and
      inhalation exposure. Published reports reveal excess cancer risk. METHODS: Using
      published findings exposure response was derived for each attributable cancer
      site. Aggregate excess lifetime risk was estimated by applying a lifetable
      calculation. RESULTS: Cancer sites contributing the most attributable cases were
      larynx, esophagus, brain, female breast, and uterine cervix. With constant
      workplace MWF exposure of 0.1 mg/m3 over a 45 years working life, the risk of
      attributable cancer was 3.7% or, excluding the less certain female cancers, 3.1%.
      CONCLUSION: Substantial cancer risks occurred at 0.1 mg/m3 MWF, one fourth of the
      current NIOSH recommended exposure limit for MWF total particulate. Because
      ingredients in current MWF remain from earlier formulations, it is likely that
      some MWF carcinogenicity persists today. Although important changes have
      occurred, newer agents are being continually introduced with little or no
      knowledge of chronic health risks.

PMID- 29327472
TI  - Mesenchymal stem cell deficiency influences megakaryocytopoiesis through the
      TNFAIP3/NF-kappaB/SMAD pathway in patients with immune thrombocytopenia.
AB  - Immune thrombocytopenia (ITP) is an autoimmune disease. Mesenchymal stem cells
      (MSCs) play important roles in the physiology and homeostasis of the
      haematopoietic system, including supporting megakaryocytic differentiation from
      CD34+ haematopoietic progenitor cells. Tumour necrosis factor alpha-induced
      protein 3 (TNFAIP3, also termed A20) plays a key role in terminating NF-kappaB
      signalling. Human genetic studies showed that the polymorphisms of the TNFAIP3
      gene may contribute to ITP susceptibility. In this study, we showed a significant
      decrease in TNFAIP3 and increase in NF-kappaB/SMAD7 in ITP-MSCs. In co-cultures
      with CD34+ cells, NF-kappaB was overexpressed in MSCs from healthy controls (HC
      MSCs) after transfection with NFKBIA (IkappaB)-specific short hairpin (sh)RNAs,
      resulting in MSC deficiency and a reduction in megakaryocytic differentiation and
      thrombopoiesis. Knockdown of TNFAIP3 expression using TNFAIP3-specific shRNAs in
      HC-MSCs affected megakaryocytopoiesis. However, IKBKB knockdown corrected
      megakaryocytopoiesis inhibition in the ITP-MSCs by decreasing NF-kappaB
      expression. Amplified TNFAIP3 expression in ITP-MSCs by TNFAIP3 cDNA can
      facilitate megakaryocyte differentiation. shRNA-mediated knockdown of SMAD7
      expression rescued the impaired MSC function in ITP patients. Therefore, we
      demonstrate that a pathological reduction in TNFAIP3 levels induced NF
      kappaB/SMAD7 pathway activation, causing a deficiency in MSCs in ITP patients.
      The ability of ITP-MSCs to support megakaryocytic differentiation and
      thrombopoiesis of CD34+ cells was impaired.

PMID- 29327474
TI  - Long-term effects of intralymphatic immunotherapy (ILIT) on canine atopic
      dermatitis.
AB  - BACKGROUND: Subcutaneous allergen immunotherapy (SCIT) is an established and
      efficacious therapy for canine atopic dermatitis (AD). In humans, intralymphatic
      immunotherapy (ILIT) was reported to be associated with fewer and less severe
      adverse effects than subcutaneous allergen immunotherapy and to be efficacious
      for several years after three intralymphatic injections. OBJECTIVE: To evaluate
      safety and effects of ILIT in a case series of dogs with (AD). ANIMALS: Fifty one
      privately owned dogs with AD. METHODS: Dogs received injections of 0.2 mL alum
      precipitated allergen extract into the popliteal lymph nodes at monthly intervals
      for 3-5 months. Lesion scores, pruritus and medication scores were determined
      before and at three and 12 months after beginning immunotherapy, and compared in
      a per protocol analysis (PP) and an intention-to-treat analysis (ITT). RESULTS:
      Twenty two dogs completed the study and 29 dogs did not fulfil study completion
      criteria due to lack of a final study visit (21 of 29) or due to insufficient
      improvement (14 of 29). All scores improved during the study with both analyses.
      For pruritus and Quality of Life scores this improvement was significant with
      both analyses; for Canine Atopic Dermatitis Extent and Severity Index (CADESI)-03
      values and medication scores only with PP. The only rare adverse effects observed
      included mild swelling of the lymph node post-injection and increased pruritus.
      CONCLUSION AND CLINICAL RELEVANCE: ILIT is safe and feasible, and provides long
      lasting relief in some atopic dogs with a limited number of injections.

PMID- 29327475
TI  - Tuning the Activity of Carbon for Electrocatalytic Hydrogen Evolution via an
      Iridium-Cobalt Alloy Core Encapsulated in Nitrogen-Doped Carbon Cages.
AB  - Graphene, a 2D material consisting of a single layer of sp2 -hybridized carbon,
      exhibits inert activity as an electrocatalyst, while the incorporation of
      heteroatoms (such as N) into the framework can tune its electronic properties.
      Because of the different electronegativity between N and C atoms, electrons will
      transfer from C to N in N-doped graphene nanosheets, changing inert C atoms
      adjacent to the N-dopants into active sites. Notwithstanding the achieved
      progress, its intrinsic activity in acidic media is still far from Pt/C. Here, a
      facile annealing strategy is adopted for Ir-doped metal-organic frameworks to
      synthesize IrCo nanoalloys encapsulated in N-doped graphene layers. The highly
      active electrocatalyst, with remarkably reduced Ir loading (1.56 wt%), achieves
      an ultralow Tafel slope of 23 mV dec-1 and an overpotential of only 24 mV at a
      current density of 10 mA cm-2 in 0.5 m sulfuric acid solution. Such superior
      performance is even superior to the noble-metal catalyst Pt. Surface structural
      and computational studies reveal that the superior behavior originates from the
      decreased DeltaGH* for HER induced by the electrons transferred from the alloy
      core to the graphene layers, which is beneficial for enhancing C?H binding.

PMID- 29327476
TI  - O-GlcNAcylation in oral squamous cell carcinoma.
AB  - BACKGROUND: Two post-translational mechanisms commonly demonstrated in various
      cancers are protein phosphorylation and glycosylation by O-linked beta-N
      acetylglucosamine (O-GlcNAc). However, only phosphorylation of the epidermal
      growth factor receptor (EGFR)/Akt pathway has been reported in oral squamous cell
      carcinoma (OSCC). Therefore, we aimed to determine both post-translational
      modifications in OSCC tissues and in oral cancer cells compared to normal tissues
      and oral keratinocytes and to find correlations of these modifications with
      histological grading. METHODS: Thirty-two OSCC and ten normal formalin-fixed and
      paraffin-embedded sections were probed with the anti-O-GlcNAc, anti-O-GlcNAc
      transferase (OGT), anti-phosphorylated-EGFRtyr1173 , and anti-phosphorylated
      Aktser473 antibodies following standard immunohistochemistry. The
      immunohistochemical (IHC) score was determined using the Fromowitz standard.
      Whole cell lysates of oral cancer cells and normal oral keratinocytes were
      immunoblotted with the anti-O-GlcNAc antibody. RESULTS: The median IHC scores of
      O-GlcNAc or OGT between OSCC and normal tissues were not different, whereas those
      of phosphorylated-EGFRtyr1173 and phosphorylated-Aktser473 were significantly
      higher in OSCC than normal tissues (P < .001 and P < .01, respectively).
      Similarly, expression of O-GlcNAcylated proteins in oral cancer cells and normal
      oral keratinocytes did not differ. In the OSCC group, the median IHC scores of O
      GlcNAc and OGT were significantly lower than those of phosphorylated-EGFRtyr1173
      and phosphorylated-Aktser473 (P < .01 and P < .001, respectively). The IHC scores
      of O-GlcNAc or OGT were not determined to correlate with histological grading.
      CONCLUSION: Unlike other types of cancers, our findings demonstrate that the
      levels of O-GlcNAcylation are not significantly increased in OSCC tissues or in
      oral cancer cells and are not associated with the histological grading of OSCC.

PMID- 29327477
TI  - Nitrogen sources affect productivity, desiccation tolerance and storage stability
      of Beauveria bassiana blastospores.
AB  - AIMS: Nitrogen is a critical element in industrial fermentation media. This study
      investigated the influence of various nitrogen sources on blastospore production,
      desiccation tolerance and storage stability using two strains of the cosmopolitan
      insect-pathogenic fungus Beauveria bassiana. METHODS AND RESULTS: Complex organic
      sources of nitrogen such as soy flour, autolysed yeast and cottonseed flour
      induced great numbers of blastospores after 2-3 days of fermentation, which also
      survived drying and remained viable (32-56% survival) after 9 months storage at 4
      degrees C, although variations were found between strains. Nitrogen availability
      in the form of free amino acids directly influenced blastospore production and
      resistance to desiccation. Increasing glucose and nitrogen concentrations up to
      120 and 30 g l-1 , respectively, did not improve blastospore production but
      enhanced desiccation tolerance. Cell viability after drying and upon fast
      rehydration was increased when >=25 g acid-hydrolysed casein per litre was
      supplemented in the liquid culture medium. CONCLUSIONS: These findings indicate
      that low-cost complex nitrogen compounds are suitable to enhance yeast-like
      growth by B. bassiana with good desiccation tolerance and therefore support its
      further scale-up production as a mycoinsecticide. SIGNIFICANCE AND IMPACT OF THE
      STUDY: Nitrogen is the most expensive nutrient in liquid media composition, but
      this study underscores the feasibility of using low-cost nitrogen compounds
      composed mainly of agro-industrial by-products for rapid production of
      desiccation-tolerant B. bassiana blastospores by liquid culture fermentation.

PMID- 29327478
TI  - Interventions to improve working conditions of nursing staff in acute care
      hospitals: Scoping review.
AB  - AIM: To conduct a scoping review to examine and map the interventions proposed
      for the improvement of the working conditions of nursing staff in acute care
      hospitals. BACKGROUND: The Registered Nurse Forecasting (RN4CAST) project and
      other studies have determined the impact that the nursing staff has on the
      quality of care. The nursing staff's higher levels of burnout, job
      dissatisfaction and negative perception of the quality of care provided caused
      worse health outcomes. METHODS: A scoping review was carried out. By searching in
      SCOPUS, PubMed, CINAHL, Cochrane, Dialnet and in the grey literature, 705
      potentially relevant papers were identified. The final analysis included 21
      papers and three grey documents. RESULTS: The studies analysed proposed
      interventions at the macro-management, meso-management and micro-management
      levels, although the interventions at the macro- and meso-levels produce better
      staff outcomes. CONCLUSIONS: The findings of this review can be applied to
      management at different levels: measures to improve the patient-nurse ratio at
      the macro-management level, the horizontal hierarchies at the meso-management
      level, the mind-body techniques at the micro-management level. IMPLICATIONS FOR
      NURSING MANAGEMENT: Nurse managers and leaders should implement interventions at
      different organisational levels to improve the working conditions of the nursing
      staff and other health outcomes.

PMID- 29327479
TI  - The immunological disease continuum of inflammation against self as an
      explanation for the lack of association between hidradenitis suppurativa and
      autoimmune thyroid disease.

PMID- 29327480
TI  - Membrane-active peptide PV3 efficiently eradicates multidrug-resistant
      Pseudomonas aeruginosa in a mouse model of burn infection.
AB  - The aim of this study was to evaluate the topical bactericidal activity of
      peptide PV3 against a MDR isolate of Pseudomonas aeruginosa in a mouse model of
      burn infection. The structural analysis of PV3 by circular dichroism spectroscopy
      indicated a low peptide helical content in water, whereas a high helical content
      was observed in the presence of the more hydrophobic 50% (v/v)
      trifluoroethanol/water buffer. A confocal microscopy analysis indicated that the
      main action of PV3 occurred at the membrane of bacteria. Peptide PV3 exhibited
      superior in vitro anti-Pseudomonas activity and killing kinetics as compared with
      doripenem. A single dose of the topically applied peptide PV3 (4 * MBC, 120 min)
      was found to be sufficient to eradicate MDRP. aeruginosa in a bacterially
      infected mouse burn wound model, whereas doripenem (4 * MBC) failed to eradicate
      the initial inoculum. This indicates a potent and fast PV3-associated
      bactericidal activity, contrary to doripenem. An in-depth analysis of mouse skin
      by histopathology revealed that peptide PV3 (4 * MBC) did not induce any topical
      skin toxicity. Overall, the data strongly suggest that peptide PV3 might be a
      potent candidate antimicrobial agent active on antibiotic-resistant isolates of
      pathogenic bacteria.

PMID- 29327481
TI  - The genome and microbiome of a dikaryotic fungus (Inocybe terrigena, Inocybaceae)
      revealed by metagenomics.
AB  - Recent advances in molecular methods have increased our understanding of various
      fungal symbioses. However, little is known about genomic and microbiome features
      of most uncultured symbiotic fungal clades. Here, we analysed the genome and
      microbiome of Inocybaceae (Agaricales, Basidiomycota), a largely uncultured
      ectomycorrhizal clade known to form symbiotic associations with a wide variety of
      plant species. We used metagenomic sequencing and assembly of dikaryotic fruiting
      body tissues from Inocybe terrigena (Fr.) Kuyper, to classify fungal and
      bacterial genomic sequences, and obtained a nearly complete fungal genome
      containing 93% of core eukaryotic genes. Comparative genomics reveals that I.
      terrigena is more similar to ectomycorrhizal and brown rot fungi than to white
      rot fungi. The reduction in lignin degradation capacity has been independent from
      and significantly faster than in closely related ectomycorrhizal clades
      supporting that ectomycorrhizal symbiosis evolved independently in Inocybe. The
      microbiome of I. terrigena fruiting-bodies includes bacteria with known symbiotic
      functions in other fungal and non-fungal host environments, suggesting potential
      symbiotic functions of these bacteria in fungal tissues regardless of habitat
      conditions. Our study demonstrates the usefulness of direct metagenomics analysis
      of fruiting-body tissues for characterizing fungal genomes and microbiome.

PMID- 29327482
TI  - Streptococcus oralis maintains homeostasis in oral biofilms by antagonizing the
      cariogenic pathogen Streptococcus mutans.
AB  - Bacteria residing in oral biofilms live in a state of dynamic equilibrium with
      one another. The intricate synergistic or antagonistic interactions between them
      are crucial for determining this balance. Using the six-species Zurich
      "supragingival" biofilm model, this study aimed to investigate interactions
      regarding growth and localization of the constituent species. As control, an
      inoculum containing all six strains was used, whereas in each of the further five
      inocula one of the bacterial species was alternately absent, and in the last,
      both streptococci were absent. Biofilms were grown anaerobically on
      hydroxyapatite disks, and after 64 h they were harvested and quantified by
      culture analyses. For visualization, fluorescence in situ hybridization and
      confocal laser scanning microscopy were used. Compared with the control, no
      statistically significant difference of total colony-forming units was observed
      in the absence of any of the biofilm species, except for Fusobacterium nucleatum,
      whose absence caused a significant decrease in total bacterial numbers. Absence
      of Streptococcus oralis resulted in a significant decrease in Actinomyces oris,
      and increase in Streptococcus mutans (P < .001). Absence of A. oris, Veillonella
      dispar or S. mutans did not cause any changes. The structure of the biofilm with
      regards to the localization of the species did not result in observable changes.
      In summary, the most striking observation of the present study was that absence
      of S. oralis resulted in limited growth of commensal A. oris and overgrowth of S.
      mutans. These data establish highlight S. oralis as commensal keeper of
      homeostasis in the biofilm by antagonizing S. mutans, so preventing a caries
      favoring dysbiotic state.

PMID- 29327483
TI  - Hospital nurses' information retrieval behaviours in relation to evidence based
      nursing: a literature review.
AB  - OBJECTIVE: The purpose of this literature review is to provide an overview of the
      information retrieval behaviour of clinical nurses, in terms of the use of
      databases and other information resources and their frequency of use. METHODS:
      Systematic searches carried out in five databases and handsearching were used to
      identify the studies from 2010 to 2016, with a populations, exposures and
      outcomes (PEO) search strategy, focusing on the question: In which databases or
      other information resources do hospital nurses search for evidence based
      information, and how often? RESULTS: Of 5272 titles retrieved based on the search
      strategy, only nine studies fulfilled the criteria for inclusion. The studies are
      from the United States, Canada, Taiwan and Nigeria. The results show that
      hospital nurses' primary choice of source for evidence based information is
      Google and peers, while bibliographic databases such as PubMed are secondary
      choices. Data on frequency are only included in four of the studies, and data are
      heterogenous. CONCLUSIONS: The reasons for choosing Google and peers are
      primarily lack of time; lack of information; lack of retrieval skills; or lack of
      training in database searching. Only a few studies are published on clinical
      nurses' retrieval behaviours, and more studies are needed from Europe and
      Australia.

PMID- 29327484
TI  - Factors affecting general practice collaboration with voluntary and community
      sector organisations.
AB  - Collaborative working between general practice (GP) and voluntary and community
      sector (VCS) organisations is increasingly championed as a means of primary care
      doing more with less and of addressing patients' "wicked problems". This paper
      aims to add to the knowledge base around collaborative practice between GPs and
      VCS organisations by examining the factors that aid or inhibit such
      collaboration. A case study design was used to examine the lived-experience of
      GPs and VCS organisations working collaboratively. Four cases, each consisting of
      a GP and a VCS organisation with whom they work collaboratively, were identified.
      Interviews (n = 18) and a focus group (n = 1) were conducted with staff within
      each organisation. Transcribed data were analysed thematically. Whilet there are
      similarities across cases in their use of, for example, Health Trainers and
      social prescribing, the form and function of GP-VCS collaborations were unique to
      their local context. The identified factors affecting GP-VCS collaboration
      reflect those found in previous service evaluations and the broader literature on
      partnership working; shared understanding, time and resources, trust, strong
      leadership, operational systems and governance and the "negotiation" of
      professional boundaries. While the current political environment may represent an
      opportunity for collaborations to develop, there are issues yet to be resolved
      before collaboration-especially more holistic and integrated approaches-becomes
      systematically embedded into practice.

PMID- 29327485
TI  - Right-left propensity of cardiogenic cerebral embolism in standard versus bovine
      aortic arch variant.
AB  - Left-hemispheric ischemic strokes are more frequent overall and often have a
      worse outcome than their right-hemispheric counterparts. We hypothesized that the
      right-left propensity of CE cerebral infarcts differs between patients with
      standard and bovine arch variants. We retrospectively identified all patients
      with acute stroke of the anterior circulation admitted to our primary stroke
      center between January 2011 and June 2017 who had moderate- to high-risk cardio
      embolic sources according to the SSS-TOAST classification. From amongst these
      patients, only those with available cross-sectional imaging of the aortic arch
      were included. Lesion side and patterns on diffusion-weighted magnetic resonance
      imaging were determined blinded to the aortic arch imaging. One hundred and
      nineteen patients met the TOAST criteria for moderate- or high-risk cardio
      embolic source. Of these, 58 (49%) were men and the median age was 71.9 years;
      33% of the patients had a bovine arch. The most common etiologies of CE were
      atrial fibrillation (n = 80 [67%]) and congestive heart failure with ejection
      fraction <30% (n = 18 [15%]). In patients with bovine arch there was an
      approximately 50% chance of having a right- or left-sided infarct. Although there
      was a trend towards right-sided lesions in patients with standard arches, this
      did not reach statistical significance. No statistically significant difference
      in embolic stroke laterality was demonstrated in our relatively small sample.
      Bovine arch could be an independent risk factor for cardio-embolic embolism.
      Clin. Anat. 31:310-313, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 29327486
TI  - IR-Driven Ultrafast Transfer of Plasmonic Hot Electrons in Nonmetallic Branched
      Heterostructures for Enhanced H2 Generation.
AB  - The ultrafast transfer of plasmon-induced hot electrons is considered an
      effective kinetics process to enhance the photoconversion efficiencies of
      semiconductors through strong localized surface plasmon resonance (LSPR) of
      plasmonic nanostructures. Although this classical sensitization approach is
      widely used in noble-metal-semiconductor systems, it remains unclear in
      nonmetallic plasmonic heterostructures. Here, by combining ultrafast transient
      absorption spectroscopy with theoretical simulations, IR-driven transfer of
      plasmon-induced hot electron in a nonmetallic branched heterostructure is
      demonstrated, which is fabricated through solvothermal growth of plasmonic W18
      O49 nanowires (as branches) onto TiO2 electrospun nanofibers (as backbones). The
      ultrafast transfer of hot electron from the W18 O49 branches to the TiO2
      backbones occurs within a timeframe on the order of 200 fs with very large rate
      constants ranging from 3.8 * 1012 to 5.5 * 1012 s-1 . Upon LSPR excitation by low
      energy IR photons, the W18 O49 /TiO2 branched heterostructure exhibits obviously
      enhanced catalytic H2 generation from ammonia borane compared with that of W18
      O49 nanowires. Further investigations by finely controlling experimental
      conditions unambiguously confirm that this plasmon-enhanced catalytic activity
      arises from the transfer of hot electron rather than from the photothermal
      effect.

PMID- 29327487
TI  - Reductive Carbocyclization of Homoallylic Alcohols to syn-Cyclobutanes by a Boron
      Catalyzed Dual Ring-Closing Pathway.
AB  - The organoborane-catalyzed reductive carbocyclization of homoallylic alcohols has
      been developed by using hydrosilanes as reducing reagents to provide a range of
      1,2-disubstituted arylcyclobutanes. The reaction proceeds in a cis-selective
      manner with high efficiency under mild conditions. Mechanistic studies, including
      deuterium scrambling and Hammett studies, and DFT calculations, suggest a dual
      ring-closing pathway.

PMID- 29327489
TI  - How can we protect youth from putative vaping gateway effects without denying
      smokers a less harmful option?

PMID- 29327488
TI  - Isolation of Human Photoreceptor Precursors via a Cell Surface Marker Panel from
      Stem Cell-Derived Retinal Organoids and Fetal Retinae.
AB  - Loss of photoreceptor cells due to retinal degeneration is one of the main causes
      of blindness in the developed world. Although there is currently no effective
      treatment, cell replacement therapy using stem-cell-derived photoreceptor cells
      may be a feasible future treatment option. In order to ensure safety and efficacy
      of this approach, robust cell isolation and purification protocols must be
      developed. To this end, we previously developed a biomarker panel for the
      isolation of mouse photoreceptor precursors from the developing mouse retina and
      mouse embryonic stem cell cultures. In the current study we applied this approach
      to the human pluripotent stem cell (hPSC) system, and identified novel biomarker
      combinations that can be leveraged for the isolation of human photoreceptors.
      Human retinal samples and hPSC-derived retinal organoid cultures were screened
      against 242 human monoclonal antibodies using a high through-put flow cytometry
      approach. We identified 46 biomarkers with significant expression levels in the
      human retina and hPSC differentiation cultures. Human retinal cell samples,
      either from fetal tissue or derived from embryonic and induced pluripotent stem
      cell cultures, were fluorescence-activated cell sorted (FACS) using selected
      candidate biomarkers that showed expression in discrete cell populations.
      Enrichment for photoreceptors and exclusion of mitotically active cells was
      demonstrated by immunocytochemical analysis with photoreceptor-specific
      antibodies and Ki-67. We established a biomarker combination, which enables the
      robust purification of viable human photoreceptors from both human retinae and
      hPSC-derived organoid cultures. Stem Cells 2018;36:709-722.

PMID- 29327490
TI  - Fetal subcutaneous cells have potential for autologous tissue engineering.
AB  - Major congenital malformations affect up to 3% of newborns. Infants with
      prenatally diagnosed soft tissue defects should benefit from having autologous
      tissue readily available for surgical implantation in the perinatal period. In
      this study, we investigate fetal subcutaneous cells as cellular source for tissue
      engineering. Fetal subcutaneous biopsies were collected from elective
      terminations at gestational Week 20-21. Cells were isolated, expanded, and
      characterized in vitro. To determine cell coverage, localization, viability, and
      proliferation in different constructs, the cells were seeded onto a matrix (small
      intestine submucosa) or in collagen gel with or without poly(epsilon
      caprolactone) mesh and were kept in culture for up to 8 weeks before analysis.
      Angiogenesis was analysed through a tube-forming assay. Fetal subcutaneous cells
      could be expanded until 43 +/- 3 population doublings, expressed mesenchymal
      markers, and readily differentiate into adipogenic and osteogenic lineages. The
      cells showed low adherence to small intestine submucosa and did not migrate deep
      into the matrix. However, in collagen gels, the cells migrated into the gel and
      proliferated with sustained viability for up to 8 weeks. The cells in the
      matrices expressed Ki67, CD73, and alpha-smooth muscle actin but not cytokeratin
      or CD31. Fetal cells derived from subcutaneous tissue demonstrated favourable
      characteristics for preparation of autologous tissue transplants before birth.
      Our study supports the theory that cells could be obtained from the fetus during
      pregnancy for tissue engineering purposes after birth. In a future clinical
      situation, autologous transplants could be used for reconstructive surgery in
      severe congenital malformations.

PMID- 29327491
TI  - Assessment of the dissipation, pre-harvest interval and dietary risk of
      carbosulfan, dimethoate, and their relevant metabolites in greenhouse cucumber
      (Cucumis sativus L.).
AB  - BACKGROUND: The dissipation behavior, pre-harvest interval and dietary risk of
      carbosulfan, dimethoate, and their relevant metabolites were investigated in
      greenhouse cucumber in Tianjin, northern China, to ensure raw consumption safety.
      RESULTS: Carbosulfan was metabolized to carbofuran, dibutylamine, 3
      hydroxycarbofuran and 3-ketocarbofuran, and dimethoate was degraded to omethoate
      in cucumber fruits and leaves. The dissipation of carbosulfan, carbofuran, 3
      hydroxycarbofuran and dimethoate fitted first-order kinetics well, with R2
      ranging from 0.912 to 0.992, and their half-lives were 2.6, 2.7, 2.4 and 5.2 days
      in cucumber fruits and 2.8, 3.0, 4.6 and 2.5 days in leaves, respectively. The
      estimated daily intakes of the active ingredients and their relevant metabolites
      were 0.1-4% of the corresponding acceptable daily intakes. Acute oral exposure to
      carbofuran (a metabolite of carbosulfan) represented 367% of the acute reference
      dose (ARfD) for 1-6-year-old Chinese children and 227% for the general Chinese
      population. CONCLUSION: A minimum pre-harvest interval of 12 days for carbosulfan
      is proposed to ensure safe consumption of cucumber. The slow dissipation rate of
      omethoate in cucumber reveals that a longer pre-harvest interval (>= 27 days) is
      necessary to prevent dietary risk when dimethoate is applied to cucumber. (c)
      2018 Society of Chemical Industry.

PMID- 29327492
TI  - A five-gene signature may predict sunitinib sensitivity and serve as prognostic
      biomarkers for renal cell carcinoma.
AB  - Sunitinib resistance is, nowadays, the major challenge for advanced renal cell
      carcinoma patients. Illuminating the potential mechanisms and exploring effective
      strategies to overcome sunitinib resistance are highly desired. We constructed a
      reliable gene signature which may function as biomarkers for prediction of
      sunitinib sensitivity and clinical prognosis. The gene expression profiles were
      obtained from The Cancer Genome Atlas database. By performing GEO2R analysis,
      numerous differentially expressed genes (DEGs) were found to be associated with
      sunitinib resistance. To acquire more precise DEGs, we integrated three different
      microarray datasets. Functional analysis revealed that these DEGs were mainly
      involved in Rap1 signaling pathway, p53 signaling pathway and Ras signaling
      pathway. Then, top five hub genes, BIRC5, CD44, MUC1, TF, CCL5, were identified
      from protein-protein interaction (PPI) network. Sub-network analysis carried out
      by MCODE plugin revealed that key DEGs were related with PI3K-Akt signaling
      pathway, Rap1 signaling pathway and VEGF signaling pathway. Next, we established
      sunitinib-resistant OS-RC-2 and 786-O cell lines and validated the expression of
      five hub genes in cell lines. To further evaluate the potentials of five-gene
      signature for predicting clinical prognosis, we analyzed RCC patients with gene
      expressions and overall survival information from two independent patient
      datasets. The Kaplan-Meier estimated the OS of RCC patients in the low- and high
      risk groups according to gene expression signature. Multivariate Cox regression
      analysis indicated that the prognostic power of five-gene signature was
      independent of clinical features. In conclusion, we developed a five-gene
      signature which can predict sunitinib sensitivity and OS for advanced RCC
      patients, providing novel insights into understanding of sunitinib-resistant
      mechanisms and identification of RCC patients with poor prognosis.

PMID- 29327493
TI  - A prospective cohort study of 122 adult patients presenting to an
      otolaryngologist's office with globus pharyngeus.
AB  - OBJECTIVES: To investigate the epidemiology of globus pharyngeus in adult
      patients presenting to the otolaryngologist's office. Also, the predictors of
      persisting symptoms, prevalence of anxiety and the effect of clinical assessment
      were analysed. DESIGN: This was a prospective cohort study. Follow-up was carried
      out using a postal questionnaire. SETTING: One otolaryngologists' office
      comprising three medical doctors. PARTICIPANTS: A total of 122 consecutive globus
      patients presenting to one otolaryngology office in a 1-year period. MAIN OUTCOME
      MEASURES: Globus incidence, gender and age distribution, predictors of persisting
      symptoms and the patient's health-related concerns. RESULTS: 3.8% of first-time
      visits were regarding globus. The mean age was 48 years [range 20-88 years], and
      a female predominance was found (ratio 1.49). Eighty-four per cent experienced
      anxiety, mainly due to fear of cancer. The most common pathological findings were
      reflux (15.6%) and post-infectious inflammation (10.6%). 21.4% of questionnaire
      responders reported full remission of their symptoms. Three predictors regarding
      symptom persistence were identified: male gender (OR 1.52), smoking (OR 3.4) and
      difficulties in breathing (OR 8.7). Patients with concomitant foreign body
      sensation were less likely to have persisting symptoms (OR 0.42). No cases of
      malignant disease were encountered. 94.7% was reassured by the office visit.
      CONCLUSION: The incidence of globus is 3.8% in the otolaryngologist's office.
      Female gender and concomitant foreign body sensation were predictive for
      presenting to the clinic even if symptom remission had occurred. Male gender,
      smoking and self-perceived breathing difficulties were predictive for persisting
      symptoms. Globus is an anxiety-causing symptom, but reassurance is provided by
      clinical examination by the otolaryngologist.

PMID- 29327494
TI  - Wood's lamp examination: a novel diagnostic approach to detect Bitot's spots in
      vitamin A deficiency.

PMID- 29327495
TI  - Challenge and hindrance demands lead to employees' health and behaviours through
      intrinsic motivation.
AB  - Based on the job demand-resource theory, this study examined the differential
      relationships of two types of job demands, challenge and hindrance stressors,
      with three outcomes: ill health, organizational citizenship behaviour, and work
      engagement. These relationships were mediated by two personal resources:
      psychological empowerment and organization-based self-esteem (OBSE). Data were
      collected at two separate points, 2 weeks apart. With 336 full-time U.S.
      employees, results from path analysis indicated that the challenge stressor,
      workload, was positively related to psychological empowerment and OBSE, both of
      which were in turn positively related to good work behaviours as well as
      negatively related to ill health, an indication that employees experienced
      physical symptoms and psychological strains. In contrast, hindrance stressors
      (role stressors and interpersonal conflict) showed the opposite patterns of
      relationships with these intermediate outcomes, resulting in less empowerment and
      OBSE. Overall, findings suggested that psychological empowerment and OBSE were
      important intrinsic motivational mechanisms through which some stressors
      (especially hindrance demands) can promote employees' favourable work behaviours
      as well as alleviate the negative health outcomes.

PMID- 29327496
TI  - Modulation of BACE1 Activity by Chemically Modified Aptamers.
AB  - A modified DNA aptamer that binds BACE1, a therapeutic target involved in
      Alzheimer's disease has been developed. This ssXNA not only tightly binds to
      BACE1 but also inhibits its protease activity in vitro in the same range as a
      previously described unmodified aptamer. We report the in vitro selection of
      functional oligonucleotides incorporating two nucleobase modifications: 5
      chlorouracil and 7-deazaadenine. The nucleoside analogue 5-chloro-2'-deoxyuridine
      has already been explored as a replacement for thymidine in a chemically modified
      genome of a bacterium. Thus, 5-chlorouracil modification is a good candidate to
      support genetic transfer in vivo as well as functional activity.

PMID- 29327497
TI  - Congenital central hypoventilation syndrome: Broader cognitive deficits revealed
      by parent controls.
AB  - OBJECTIVE: To investigate neurocognitive deficits in children with Congenital
      Central Hypoventilation Syndrome (CCHS) by comparing them to their parents, since
      parents comprise a particularly suitable control group matched on disease
      extrinsic factors that can influence neurocognitive functioning. We compared CCHS
      patients to their parents and to population norms, hypothesizing that they would
      obtain lower intelligence test scores than both groups. We also compared patient
      parent differences against patient-normative differences, to determine whether
      the two analytic approaches would yield different results. METHODS: We
      administered an intelligence screening, the Shipley-2, to 21 school-aged patients
      (age 14.2 +/- 5.5 years) with PHOX2B mutation-confirmed CCHS and their parents.
      Patients also received detailed clinical intellectual assessments using the
      Wechsler scales. RESULTS: CCHS patients scored significantly below parents on
      Shipley-2 indices of intelligence, vocabulary, and abstraction, with a trend for
      perceptual reasoning. The CCHS patients scored significantly below population
      norms on indices of abstraction and perceptual reasoning. Patient-parent
      differences were significantly larger than patient-normative differences for
      vocabulary scores. CCHS patients scored significantly below population norms on
      Wechsler indices of intelligence, perceptual reasoning, working memory, and
      processing speed. CONCLUSIONS: CCHS may affect a broader range of cognitive
      abilities than previous research based on comparisons to population norms has
      indicated. Comparisons of CCHS children to their parents reveal deficits of
      vocabulary and abstract reasoning which have not been previously identified. A
      full understanding of the neurocognitive impact of CCHS requires comparisons
      between patients and other individuals such as friends, parents, or siblings who
      closely resemble them on disease-extrinsic characteristics.

PMID- 29327499
TI  - Five-year outcome of endoscopic laser cricopharyngeal myotomy: Our experience in
      ten patients.

PMID- 29327498
TI  - Relationship style and glycaemic control in women with type 2 diabetes: The
      mediating role of psychological distress.
AB  - This study examined whether depressive symptoms and/or diabetes distress mediate
      the association between relationship style and glycaemic control in women with
      diabetes. Seventy-five women with type 2 diabetes completed the Relationship
      Questionnaire. Participants endorsing "secure" or "preoccupied" adult attachment
      were combined into the interactive relationship style and "dismissing/avoidant"
      or "fearful" adult attachment were combined into the independent relationship
      style. Glycaemic control was a latent variable composed of A1c and 48-hr
      continuously measured glucose. Diabetes distress was assessed with the Problem
      Areas in Diabetes scale and depressive symptoms with the Center for
      Epidemiological Studies Depression scale. A parallel multiple mediation model
      with relationship style as the independent variable, glycaemic control as the
      dependent variable, and Problem Areas in Diabetes and Center for Epidemiological
      Studies Depression scale as mediators, tested indirect effects. Bias-corrected
      bootstrap with 10,000 replications was used to construct 95% confidence
      intervals. The indirect association of relationship style with glycaemic control
      through diabetes distress was significant (effect = -0.09, p = .036, 95CI = -0.19
      0.01), but through depressive symptoms was not. A model testing the indirect
      association of relationship style with diabetes distress through glycaemic
      control was not significant. Results suggest that relationship style is
      associated with glycaemic control through diabetes distress in women with type 2
      diabetes.

PMID- 29327501
TI  - Corrigendum.

PMID- 29327500
TI  - Multiplex polymerase chain reaction detection of selected bacterial species from
      symptomatic and asymptomatic non-vital teeth with primary endodontic infections.
AB  - AIM: The aim of the present study was to investigate the presence of selective
      anaerobic microorganisms in primary root canal infections of symptomatic and
      asymptomatic non-vital teeth with periapical pathosis using multiplex polymerase
      chain reaction. METHODS: A total of 100 root canal samples (50 from symptomatic
      and 50 from asymptomatic teeth) were obtained from patients with primary
      endodontic infections. DNA extracted from the samples was amplified by using
      specific primers for the 16S rRNA gene of each bacterium, and semiquantification
      was done to analyze the prevalence of microorganisms and their correlation to
      clinical features. RESULTS: Treponema denticola (T. denticola) was present in 21
      (42%) and 29 (58%) samples in the symptomatic and asymptomatic groups,
      respectively. Tannerella forsythia, Porphyromonas gingivalis (P. gingivalis), and
      Fusobacterium nucleatum (F. nucleatum) were significantly high (P < .05) in the
      symptomatic group, whereas Prevotella intermedia was significantly high (P < .05)
      in the asymptomatic group. The mean counts of T. denticola and F. nucleatum were
      significantly high (P < .05) in the symptomatic group. For symptoms, P.
      gingivalis, T. denticola, and F. nucleatum were significantly associated with
      clinical features. CONCLUSION: Significant differences exist in the bacterial
      composition between asymptomatic and symptomatic primary endodontic infections.
      As well as presence of pathogens, other factors, such as the phenotypic trait of
      bacteria and interactions among bacterial members, might play a determining role
      in the pathogenicity of primary endodontic infections.

PMID- 29327502
TI  - A differential diagnosis of a head and neck bony lesion: Review of a case series
      with 18 patients with extraintestinal features of familial adenomatous polyposis.

PMID- 29327504
TI  - Natural Deposition Strategy for Interfacial, Self-Assembled, Large-Scale, Densely
      Packed, Monolayer Film with Ligand-Exchanged Gold Nanorods for In Situ Surface
      Enhanced Raman Scattering Drug Detection.
AB  - Liquid interfacial self-assembly of metal nanoparticles holds great promise for
      its various applications, such as in tunable optical devices, plasmonics,
      sensors, and catalysis. However, the construction of large-area, ordered,
      anisotropic, nanoparticle monolayers and the acquisition of self-assembled
      interface films are still significant challenges. Herein, a rapid, validated
      method to fabricate large-scale, close-packed nanomaterials at the
      cyclohexane/water interface, in which hydrophilic cetyltrimethylammonium bromide
      coated nanoparticles and gold nanorods (AuNRs) self-assemble into densely packed
      2D arrays by regulating the surface ligand and suitable inducer, is reported.
      Decorating AuNRs with polyvinylpyrrolidone not only extensively decreases the
      charge of AuNRs, but also diminishes repulsive forces. More importantly, a
      general, facile, novel technique to transfer an interfacial monolayer through a
      designed in situ reaction cell linked to a microfluidic chip is revealed. The
      self-assembled nanofilm can then automatically settle on the substrate and be
      directly detected in the reaction cell in situ by means of a portable Raman
      spectrometer. Moreover, a close-packed monolayer of self-assembled AuNRs provides
      massive, efficient hotspots to create great surface-enhanced Raman scattering
      (SERS) enhancement, which provides high sensitivity and reproducibility as the
      SERS-active substrate. Furthermore, this strategy was exploited to detect drug
      molecules in human urine for cyclohexane-extracted targets acting as the oil
      phase to form an oil/water interface. A portable Raman spectrometer was employed
      to detect methamphetamine down to 100 ppb levels in human urine, exhibiting
      excellent practicability. As a universal platform, handy tool, and fast
      pretreatment method with a good capability for drug detection in biological
      systems, this technique shows great promise for rapid, credible, and on-spot drug
      detection.

PMID- 29327505
TI  - Flexible Modulation of CO-Release Using Various Nuclearity of Metal Carbonyl
      Clusters on Graphene Oxide for Stroke Remediation.
AB  - Utilizing the size-dependent adsorption properties of ruthenium carbonyl clusters
      (Ru-carbon monoxide (CO)) onto graphene oxide (GO), a facile CO-release platform
      for in situ vasodilation as a treatment for stroke-related vascular diseases is
      developed. The rate and amount of formation of the CO-release-active RuII (CO)2
      species can be modulated by a simple mixing procedure at room temperature. The
      subsequent thermally induced oxidation of RuII (CO)2 to RuO2 on the GO surface
      results in the release of CO. Further modulation of thermal and CO-release
      properties can be achieved via a hybridization of medium- and high-nuclearity of
      Ru-CO clusters that produces a RuO2 /RuII (CO)2 /6 Ru-CO-GO composite, where 6 Ru
      CO-GO provides a photothermally activated reservoir of RuII (CO)2 species and the
      combined infrared absorption properties of GO and RuO2 provides photothermal
      response for in situ CO-release. The RuO2 /RuII (CO)2 /6 Ru-CO-GO composite does
      not produce any cytotoxicity and the efficacy of the composite is further
      demonstrated in a cortical photothrombotic ischemia rat model.

PMID- 29327506
TI  - Next generation sequencing characterizes the extent of HLA diversity in an
      Argentinian registry population.
AB  - Next generation DNA sequencing is used to determine the HLA-A, -B, -C, -DRB1, and
      -DQB1 assignments of 1472 unrelated volunteers for the unrelated donor registry
      in Argentina. The analysis characterized all HLA exons and introns for class I
      alleles; at least exons 2, 3 for HLA-DRB1; and exons 2 to 6 for HLA-DQB1. Of the
      distinct alleles present, there are 330 class I and 98 class II. The majority
      (~98%) of the cumulative allele frequency at each locus is contributed by alleles
      that appear at a frequency of at least 1 in 1000. Fourteen (18.2%) of the 77
      novel class I and II alleles carry nonsynonymous variation within their exons; 52
      (75.4%) class I novel alleles carry only single, apparently random, nucleotide
      variation within their introns/untranslated regions. Alleles encoding protein
      variation not usually detected by typing focused only on the exons encoding the
      antigen recognition domain are 1.0% of the class I assignments and 7.3% of the
      class II assignments (predominantly DQB1*02:02:01, DQB1*03:19:01, and
      DRB1*14:54:01). Updates to the common and well documented list of alleles include
      10 alleles previously thought to be uncommon but that are found at least 30
      times. Five locus haplotypes estimated using the expectation-maximization
      algorithm as present 3 or more times total 187. While the known HLA diversity
      continues to increase, the conservation of known allele sequences is remarkable.
      Overall, the HLA diversity observed in the Argentinian population reflects its
      European and Native American ancestry.

PMID- 29327507
TI  - Rapid characterization of chlorogenic acids in Duhaldea nervosa based on ultra
      high-performance liquid chromatography-linear trap quadropole-Orbitrap-mass
      spectrometry and mass spectral trees similarity filter technique.
AB  - Duhaldea nervosa (Wallich ex Candolle) A. Anderberg has been traditionally used
      as a food spice and also in folk medicine for treating traumatic injury and
      relieving rheumatism, especially accelerating the healing of a fracture. However,
      so far as we are aware, the chemical constituents have not been fully
      investigated. In this study, a practical method of mass spectral trees similarity
      filter, a data-mining technique, was developed and evaluated for the rapid
      detection and identification complicated constituents based on ultra-high
      performance liquid chromatography-linear trap quadropole-Orbitrap-mass
      spectrometry. Finally, a total of 47 chlorogenic acids, including 19 monoacyl
      quinic acids, 22 diacyl-quinic acids, and six triacyl-quinic acids, were
      unambiguously or tentatively identified based on their accurate mass measurement,
      chromatographic retention, MSn spectra, and bibliography data. To our best
      knowledge, it is the first time to report the chlorogenic acids of D. nervosa,
      which would be beneficial for the further material basis and quality research.
      Meanwhile, this mass spectral trees similarity filter method could be envisioned
      to exhibit a wide application for the identification of complicated components
      from botanical extracts.

PMID- 29327508
TI  - Relative stability of ploidy in a marine Synechococcus across various growth
      conditions.
AB  - Marine picocyanobacteria of the genus Synechococcus are ubiquitous phototrophs in
      oceanic systems. Consistent with these organisms occupying vast tracts of the
      nutrient impoverished ocean, most marine Synechococcus so far studied are
      monoploid, i.e., contain a single chromosome copy. The exception is the
      oligoploid strain Synechococcus sp. WH7803, which on average possesses around 4
      chromosome copies. Here, we set out to understand the role of resource
      availability (through nutrient deplete growth) and physical stressors (UV,
      exposure to low and high temperature) in regulating ploidy level in this strain.
      Using qPCR to assay ploidy status we demonstrate the relative stability of
      chromosome copy number in Synechococcus sp. WH7803. Such robustness in
      maintaining an oligoploid status even under nutrient and physical stress is
      indicative of a fundamental role, perhaps facilitating recombination of damaged
      DNA regions as a result of prolonged exposure to oxidative stress, or allowing
      added flexibility in gene expression via possessing multiple alleles.

PMID- 29327503
TI  - Noncoding RNAs in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the main
      cause of dementia among the elderly worldwide. Despite intense efforts to develop
      drugs for preventing and treating AD, no effective therapies are available as
      yet, posing a growing burden at the personal, medical, and socioeconomic levels.
      AD is characterized by the production and aggregation of amyloid beta (Abeta)
      peptides derived from amyloid precursor protein (APP), the presence of
      hyperphosphorylated microtubule-associated protein Tau (MAPT), and chronic
      inflammation leading to neuronal loss. Abeta accumulation and hyperphosphorylated
      Tau are responsible for the main histopathological features of AD, Abeta plaques,
      and neurofibrillary tangles (NFTs), respectively. However, the full spectrum of
      molecular factors that contribute to AD pathogenesis is not known. Noncoding
      (nc)RNAs, including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and
      circular RNAs (circRNAs), regulate gene expression at the transcriptional and
      posttranscriptional levels in various diseases, serving as biomarkers and
      potential therapeutic targets. There is rising recognition that ncRNAs have been
      implicated in both the onset and pathogenesis of AD. Here, we review the ncRNAs
      implicated posttranscriptionally in the main AD pathways and discuss the growing
      interest in targeting regulatory ncRNAs therapeutically to combat AD pathology.
      WIREs RNA 2018, 9:e1463. doi: 10.1002/wrna.1463 This article is categorized
      under: RNA in Disease and Development > RNA in Disease.

PMID- 29327509
TI  - Proteomic expression profile of injured rat peripheral nerves revealed biological
      networks and processes associated with nerve regeneration.
AB  - Peripheral nerve regeneration is regulated through the coordinated spatio
      temporal activation of multiple cellular pathways. In this work, an integrated
      proteomics and bioinformatics approach was employed to identify differentially
      expressed proteins at the injury-site of rat sciatic nerve at 20 days after
      damage. By a label-free liquid chromatography mass-spectrometry (LC-MS/MS)
      approach, we identified 201 differentially proteins that were assigned to
      specific canonical and disease and function pathways. These include proteins
      involved in cytoskeleton signaling and remodeling, acute phase response, and
      cellular metabolism. Metabolic proteins were significantly modulated after nerve
      injury to support a specific metabolic demand. In particular, we identified a
      group of proteins involved in lipid uptake and lipid storage metabolism.
      Immunofluorescent staining for acyl-CoA diacylglycerol acyltransferase 1 (DGAT1)
      and DAGT2 expression provided evidence for the expression and localization of
      these two isoforms in Schwann cells at the injury site in the sciatic nerve. This
      further supports a specific local regulation of lipid metabolism in peripheral
      nerve after damage.

PMID- 29327511
TI  - Cp2 TiX Complexes for Sustainable Catalysis in Single-Electron Steps.
AB  - We present a combined electrochemical, kinetic, and synthetic study with a novel
      and easily accessible class of titanocene catalysts for catalysis in single
      electron steps. The tailoring of the electronic properties of our Cp2 TiX
      catalysts that are prepared in situ from readily available Cp2 TiX2 is achieved
      by varying the anionic ligand X. Of the complexes investigated, Cp2 TiOMs proved
      to be either equal or substantially superior to the best catalysts developed
      earlier. The kinetic and thermodynamic properties pertinent to catalysis have
      been determined. They allow a mechanistic understanding of the subtle interplay
      of properties required for an efficient oxidative addition and reduction.
      Therefore, our study highlights that efficient catalysts do not require the
      elaborate covalent modification of the cyclopentadienyl ligands.

PMID- 29327512
TI  - Mental disorder: Are we moving away from distress and disability?
AB  - The first time that formally a definition of mental disorder was presented was in
      DSM-III. This resulted from a complex conceptual analysis carried out by Spitzer,
      chair of the committee on nomenclature and statistics. The criteria of harm
      (distress-disability) arise as main defining characteristics for mental illness,
      being added that "there is an inference" that there is a dysfunction. The
      distress-disability model was later developed by Wakefield. This author argued
      that in a medical or psychiatric disorder there had to be a dysfunctional
      component (value free) and another one of harm (value laden). In this article, we
      intend to review the emergence and evolution of the definition of mental disorder
      and the importance that the criteria of distress and disability always had in
      this definition. This happened until the advent of DSM-5 when these criteria came
      to play a secondary role.

PMID- 29327510
TI  - ZmSTK1 and ZmSTK2, encoding receptor-like cytoplasmic kinase, are involved in
      maize pollen development with additive effect.
AB  - Pollen germination and pollen tube growth are important physiological processes
      of sexual reproduction of plants and also are involved in signal transduction.
      Our previous study reveals that ZmSTK1 and ZmSTK2 are two receptor-like
      cytoplasmic kinases (RLCK) homologs in Zea mays as members of receptor-like
      protein kinase (RLK) subfamily, sharing 86% identity at the amino acid level.
      Here, we report that ZmSTK1 and ZmSTK2, expressed at late stages of pollen
      development, regulate maize pollen development with additive effect. ZmSTK1 or
      ZmSTK2 mutation exhibited severe pollen transmission deficiency, which thus
      influenced pollen fertility. Moreover, the kinase domains of ZmSTKs were cross
      interacted with C-terminus of enolases detected by co-immunoprecipitation (Co-IP)
      and yeast two-hybrid system (Y2H), respectively. Further, the detective ZmSTK1 or
      ZmSTK2 was associated with decreased activity of enolases and also reduced
      downstream metabolite contents, which enolases are involved in glycolytic
      pathway, such as phosphoenolpyruvate (PEP), pyruvate, ADP/ATP, starch, glucose,
      sucrose and fructose. This study reveals that ZmSTK1 and ZmSTK2 regulate maize
      pollen development and indirectly participate in glycolytic pathway.

PMID- 29327513
TI  - Methanol-Water Aqueous-Phase Reforming with the Assistance of Dehydrogenases at
      Near-Room Temperature.
AB  - As an excellent hydrogen-storage medium, methanol has many advantages, such as
      high hydrogen content (12.6 wt %), low cost, and availability from biomass or
      photocatalysis. However, conventional methanol-water reforming usually proceeds
      at high temperatures. In this research, we successfully designed a new effective
      strategy to generate hydrogen from methanol at near-room temperature. The
      strategy involved two main processes: CH3 OH->HCOOH->H2 and NADH->HCOOH->H2 . The
      first process (CH3 OH->HCOOH->H2 ) was performed by an alcohol dehydrogenase
      (ADH), an aldehyde dehydrogenase (ALDH), and an Ir catalyst. The second procedure
      (NADH->HCOOH->H2 ) was performed by formate dehydrogenase (FDH) and the Ir
      catalyst. The Ir catalyst used was a previously reported polymer complex catalyst
      [Cp*IrCl2 (ppy); Cp*=pentamethylcyclopentadienyl, ppy=polypyrrole] with high
      catalytic activity for the decomposition of formic acid at room temperature and
      is compatible with enzymes, coenzymes, and poisoning chemicals. Our results
      revealed that the optimum hydrogen generation rate could reach up to 17.8 MUmol h
      1  gcat-1 under weak basic conditions at 30  degrees C. This will have high
      impact on hydrogen storage, production, and applications and should also provide
      new inspiration for hydrogen generation from methanol.

PMID- 29327515
TI  - Myocardial Dysfunction in Sepsis and Septic Shock.

PMID- 29327514
TI  - Evolution of radical resection for perihilar cholangiocarcinoma.

PMID- 29327516
TI  - Cardiac Biomarkers and Myocardial Dysfunction in Septicemia.
AB  - Objectives: Cardiac biomarkers have been studied in sepsis in the past and
      various mechanisms for their rise have been elucidated. However their association
      with severity of sepsis, mortality and myocardial dysfunction warrants further
      studies. We have studied three different cardiac biomarkers- troponin T (trop T),
      creatine phosphokinase MB isoform (CPK MB) and NT pro brain natriuretic peptide
      (NT Pro BNP) in patients with septicemia. We have attempted to observe the levels
      of these biomarkers in sepsis, their individual abilities to predict the severity
      of sepsis, mortality and association with myocardial dysfunction noted in
      echocardiography. Results: There were 54 patients each of septicaemia and
      controls. The means of the three biomarkers, namely Troponin T, CPK MB and NT Pro
      BNP, were significantly elevated in patients with sepsis- mean values of 0.23+/
      0.8 ng/ml, 9.9+/-13.4 ng/ml and 5988.62+/-13.7 pg/ml respectively. Myocardial
      dysfunction was observed in 27 cases. There were 13 non-survivors. Troponin T and
      NT pro BNP were strongly associated with higher mortality. CPK MB had better
      correlation with myocardial dysfunction. Conclusion: We conclude that myocardial
      dysfunction using echocardiography is seen in around half of the patients with
      sepsis. Cardiac biomarkers can be routinely used in patients of septicemia to
      suggest the severity of sepsis,to detect myocardial injury and dysfunction and
      prognostication. CPK MB may be very useful to suspect myocardial dysfunction in
      such patients.

PMID- 29327517
TI  - Sheehan's Syndrome-The Most Common Cause of Panhypopituitarism at Moderate
      Altitude: A Sub-Himalayan Study.
AB  - Background: Panhypopituitarism is a rare disorder with varied clinical
      presentation having various etiologies. Sheehan's syndrome (SS) is decreasing in
      frequency worldwide and is a rare cause of panhypopituitarism in developed
      nations. Methodology: A retrospective study done between May 2011 and May 2015 in
      tertiary care hospital. We reviewed the records of patients with hypopituitarism.
      Clinical features, hormonal profile and radiological investigations noted.
      Results: Total 14 patients of panhypopituitarism included with average duration
      of symptoms 1.93+/- 1.96 years. four (28.57%) were males and ten (71.43%) were
      females with mean age of diagnosis 37.78+/- 13.68 years. Sheehan's syndrome (SS)
      was the most common cause of panhypopituitarism in 57.14%(8 patients), followed
      by post surgery in 14.28% (2 patients). 80% of women had SS with a mean duration
      of symptoms 2.39+/-1.54 years. Conclusion: Sheehan's syndrome is not uncommon in
      developing countries, High degree of clinical suspicion is desired as clinical
      features are most often subtle.

PMID- 29327518
TI  - A Study of Cardiovascular Abnormalities in HIV Positive Patients in a Tertiary
      Care Hospital in Northern India.
AB  - Introduction: Cardiovascular illness is common in patients with HIV infection,
      particularly in the later course of disease. Cardiovascular abnormalities in
      people living with HIV disease (PLHIV) often go unrecognized or untreated
      resulting in increased cardiovascular related morbidity and mortality and reduced
      quality of life. The prevalence of cardiac involvement in PLHIV has been reported
      to range between 28 to 73%. However, the incidence of symptomatic heart failure
      in HIV positive patients is 8-10%. Aims and Objectives: The present study had
      been undertaken to study the prevalence of cardiovascular manifestation in HIV
      positive patients in north Indian population and its association with HAART, CD4
      count and WHO stages of the disease. Material and Methods: This study was
      conducted in the department of Medicine, KGMU, Lucknow. A total of 75 HIV
      positive patients of age >15 years, admitted to the hospital were enrolled, out
      of which 32 were on ART. The cardiovascular evaluation in the form of chest x
      ray, ECG, 2D echocardiography and NT-ProBNP was done and their correlations with
      CD4 count was studied. Two rheumatic heart disease patients were excluded during
      analysis. Results: Cardiovascular manifestations were found in around 52.1% of
      HIV positive patients. Chest x-ray showed cardiomegaly in 8 out of 73 patients.
      ECG abnormalities were found in 49.3% while 2 D echocardiography was abnormal in
      52.1% of the patients. Though NT-Pro BNP was abnormal in 26.7% of the patients,
      no statistical correlation was found with CD4 counts. Conclusion: The prevalence
      of cardiovascular abnormalities in our study population was 52.1%. Our study did
      not show any statistical correlation with CD4 counts but showed correlation with
      the WHO clinical staging of the disease. We suggest a study with larger sample
      size to see the exact prevalence of cardiovascular disease in HIV positive
      patients.

PMID- 29327519
TI  - Psychiatric Co-morbidities in Women with Epilepsy.
AB  - Background: The co-existence of psychiatric co-morbidities with Epilepsy in women
      is multifactorial and complex, being closely related to hormonal status,
      medication side effects, and psychosocial factors. Aims: We aimed to study
      associated Psychiatric co-morbidities in women with Epilepsy (WWE), and correlate
      the same with seizure subtype and medication , compliance with treatment and
      seizure control. Material and Methods: This was a prospective, interview based
      study in OPD over 18 months, evaluating WWE over 13 years of age with at least 1
      seizure in the last 1 year. The primary outcome evaluated was the psychiatric
      diagnosis. Covariables assessed included sociodemographic data, details of
      seizures and treatment taken. Study population included 143 WWE. Thirty women
      with a chronic disease, viz., Diabetes and with no h/o seizures, and another
      group of 25 healthy women from the community with no seizures ever and no
      Diabetes, were evaluated as 2 sets of controls. Results and Conclusions: One
      hundred and forty three women with Epilepsy (WWE) were recruited into the study.
      Psychiatric co-morbidity prevalence was 28.6 % (41/143) in WWE, 13.7 % in women
      with Diabetes and 8.3 % in women with no Epilepsy or Diabetes (normal controls).
      Overall, Depression was the commonest psychiatric co-morbidity. Psychiatric co
      morbidity was significantly more in WWE as compared to normal controls. Seizure
      duration over 2 years, complex partial seizures and Polypharmacy were
      significantly linked to Psychiatric co-morbidities.

PMID- 29327520
TI  - Risk Factors of Clinical and Immunological Failure in South Indian Cohort on
      Generic Antiretroviral Therapy.
AB  - Background: Since the time of NACO Antiretroviral (ART) roll-out, generic ART has
      been the mainstay of therapy. There are many studies documenting the efficacy of
      generic ART but with the passage of time, failure of therapy is on the rise. As
      institution of second line ART has significant financial implications both for a
      program and for an individual it is imperative that we determine factors which
      contribute towards treatment failure in a cohort of patients on generic
      antiretroviral therapy. Methodology: This was a nested matched case-control study
      assessing the predictors for treatment failure in our cohort who had been on Anti
      retroviral therapy for at least a year. We identified 42 patients (Cases) with
      documented treatment failure out of our cohort of 823 patients and 42 sex, age
      and duration of therapy-matched controls. Using a structured proforma, we
      collected information from the out-patient and in-patient charts of the
      Infectious Diseases clinic Cohort in CMC, Vellore. A set of predetermined
      variables were studied as potential risk factors for treatment failure on ART.
      Results: Univariate analysis showed significant association with 1) Self-reported
      nonadherence<95% [OR 12.81 (95%CI 1.54-281.45)]. 2) Treatment interruptions in
      adherent cases (OR 9.56 (95% CI 1.11-213.35)]. 3) Past inappropriate therapies
      [OR 9.65 (95% CI 1.12-215.94)]. 4) Diarrhoea [OR 16.40 (95% CI 2.02-3.55.960]. 5)
      GI opportunistic infections (OR 11.06 (95% CI 1.31 -244.27)] and 6) Drug Toxicity
      [OR 3.69 (95% CI 1.15-12.35).In multiple logistic regression analysis, we found
      independent risk factors of treatment failure to be: Self-reported non-adherence
      (<95%) with OR 15.46(95%CI 1.55 - 154.08), drug toxicity - OR 4.13(95%CI 1.095 -
      15.534) and history of diarrhoea - OR 23.446(95%CI 2.572 - 213.70). Conclusion:
      This study reveals that besides adherence to therapy, presence of diarrhoea and
      occurrence of drug toxicity are significant risk factors associated with failure
      of anti-retroviral therapy. There is a need for further prospective studies to
      assess their role in development of treatment failure on ART and thus help
      development of targeted interventions.

PMID- 29327521
TI  - Cerebrospinal Fluid - A Clinicopathologic Analysis.
AB  - Context and Objective: This study aims to emphasize the importance of an
      appropriate CSF examination in patients of suspected CNS disease and the
      necessity of correlating it with the clinico-radiologic findings which will help
      in early diagnosis of CNS diseases and guide the further management of the
      disease. Design: In this 2 year study, 215 CSF samples from patients with
      clinically suspected diseases of the CNS were studied. The CSF samples were
      analyzed for gross examination, protein, sugar, adenosine deaminase (ADA) levels,
      microscopic examination and microbiologic examination. Culture was performed an
      all cases. A cytospin examination was done where malignancy (primary/metastasis)
      was suspected. Results: Of the 215 samples analyzed, 97(45.1%) were found to have
      abnormal CSF findings. The maximum number of abnormal CSF samples were seen in
      the adolescents and adults (56.7%) age group. Very high protein levels were seen
      with bacterial, tuberculous and parasitic meningitis whereas fungal and viral
      meningitis showed moderate elevation of proteins. CSF ADA levels were raised in
      cases of tuberculous meningitis with mean value of 20.9 IU/L whereas all other
      types of meningitis showed normal level of ADA. A total of 3 cases of IVH and 2
      cases of demyelinating disease were found in our study. Malignant cells were
      detected in two cases. Conclusion: Thus, a study of CSF is vital as it provides
      an invaluable diagnostic window to the central nervous system atmosphere. A
      timely and appropriate analysis of CSF can help the clinician to direct the line
      of treatment and enhance patient care as well as reduce morbidity and mortality.

PMID- 29327522
TI  - Clinical Profile and Outcome of Pregnant Patients with Acute HEV Hepatitis During
      Water Borne Epidemic in Himachal Pradesh: A Hospital Based Study.
AB  - Background: Recent outbreak of HEV hepatitis epidemic in Himachal Pradesh in
      Shimla caused significant morbidity and mortality especially among pregnant
      patients. Overall mortality is 0.5- 4% in patients developing acute hepatic
      failure (ALF) and is significantly higher in pregnant patients (20%). Present
      study conducted to observe clinical profile and outcome in pregnant patients.
      Methodology: this is a retrospective observational study done on admitted
      pregnant and post partum patients with acute HEV hepatitis during 3 months
      periods. History focussing on symptoms, duration, onset, progression, co
      morbidities, pregnancy outcome, complications noted. Confirmation of the HEV
      infection was done using HEV IgM ELISA. Results: Total 26 patients observed,
      among which 8 were pregnant and 18 were post partum Average age of presentation
      was 26.11+/-3.7 years and average duration of hospital stay 10.46 days. 8
      (30.76%) patients required ICU care Presenting complaints were similar to typical
      presentation in viral hepatitis. All patients were icteric at presentation and 8
      (30.76%) patients had hepatic encephalopathy (HE) and 8 (30.76%) patients had
      ALF, 20 (76.92%) sepsis and 7(26.92%) underwent preterm labour. Out of the total
      14 patients who delivered, poor fetal outcome was seen in 5 patients died during
      this period (15.38%). Factors responsible for in hospital mortality were altered
      mental status at presentation (p0.018), edema (p 0.046), HE(0.018), acute liver
      failure(0.018). Conclusion: HEV infection has more morbidity and mortality among
      pregnant females and poor fetal outcome. Mortality is high (15.38%). Altered
      mental status at presentation, edema, HE, ALF have significant correlation
      (<0.05) with the mortality.

PMID- 29327523
TI  - Association of Physicians of India: Position Statement on Role of Chirally Pure
      Molecules in Clinical Practice.
AB  - Chirally pure molecules or enantiomers are non-superimposable mirror images of
      each other with a chiral center (such as carbon, sulphur, nitrogen or phosphorous
      atom). An equimolar mixture of enantiomers forms a racemate. Chirally pure
      molecules (single enantiomers) are important in the field of drug discovery as
      the drug targets such as enzymes and receptors are enantioselective in nature.
      Clinical studies have demonstrated that chirally pure drugs exhibit different
      pharmacokinetic and metabolic profiles, reduced adverse events, improved safety
      profiles and similar therapeutic activity at lowered drug dosage as compared with
      the racemate in many therapeutic areas. However, since there is a low level of
      awareness on the advantages of chirally pure molecules among clinicians,
      pharmacists and patients in India, the Association of Physicians of India (API)
      developed this position statement to increase awareness on the concept of
      chirality and the associated advantages of using chirally pure drugs in certain
      therapeutic areas to maximize patient outcomes. This includes the clinical
      evidence associated with single enantiomers such as S-metoprolol, S-amlodipine,
      esomeprazole, escitalopram, levobupivacaine, cisatracurium, S-etodolac,
      dexketoprofen, levofloxacin in terms of efficacy and safety as compared with
      their racemates. In addition, the API also provides some tactical recommendations
      for clinicians, pharmacists, patients, regulatory body and pharmaceutical
      companies to increase awareness on chirally pure drugs and puts forth the need
      for expedited availability of chirally pure drugs in the Indian market.

PMID- 29327525
TI  - Drug Abuse as an Emanating Risk for Stroke in Young Adults.
AB  - Drug abuse is a substantial risk factor for stroke among patients under 45 years
      of age and ranks second among the most commonly identified potential risk
      factors. Drug abusers aged 15 to 44 years are 6.5 times more likely to have a
      stroke than non drug users. Stroke occurring in persons under 45 years of age
      accounts for only 4% of all strokes but causes an enormous toll in personal
      suffering, lost productivity, and health care costs.

PMID- 29327524
TI  - Uttar Pradesh Association of Physicians of India Position Statement: Tobacco Use
      and Metabolic Syndrome.
AB  - Tobacco use is one of the main preventable causes of mortality and morbidity
      worldwide. The global disease burden due to tobacco use is huge with projected
      mortality of eight million lives per year by 2030. Metabolic syndrome (MS) is
      defined as a constellation of cardiovascular and endocrine risk factors such as
      insulin resistance, obesity, raised blood pressure, and abnormal lipid profile.
      The relationship between tobacco use and MS has been well established. Also, the
      causal association between tobacco use and development of individual components
      of MS is well established. The Uttar Pradesh Association of Physicians of India
      (UP API) has drafted this position statement on managing tobacco use among
      persons with or at risk of developing Metabolic Syndrome (MS). This position
      statement presents evidence-based recommendations as described below. Scope and
      purpose The objective of this position statement is to offer clinical
      recommendations for screening, diagnosis and management of tobacco use among
      persons with or at risk of developing Metabolic Syndrome (MS). The purpose of
      this document is to aid in identification and treatment of maladaptive patterns
      of tobacco use i.e. tobacco use disorder (tobacco dependence, harmful use, abuse)
      in person with or at risk of developing MS. Intended Audience The position
      statement is targeted at the clinicians engaged in care and management of person
      with or at risk of developing Metabolic Syndrome (MS). This might also be of
      relevance to the policy makers considering the public health burden of both MS
      and tobacco use disorders.

PMID- 29327526
TI  - Dengue-Induced Hepatic Injury.
AB  - Dengue has a significant impact on the disease burden in the population residing
      in tropical countries. It is transmitted by the bite of Aedes mosquito. The virus
      have got some hepatotoxic effects. Most of the cases are asymptomatic. However,
      it should be considered as one of the causes of Acute Liver Failure in endemic
      countries. Our article focuses on the pathogenesis, manifestations,
      investigations and, the treatment options for dengue related hepatic dysfunction.

PMID- 29327527
TI  - Role and Relevance of Blood Pressure Variability in Hypertension Related Co
      morbidities.
AB  - Despite maintaining mean blood pressure at optimal levels, cardiovascular
      complications still occur in hypertensive patients. Blood pressure variability
      (BPV) has been implicated as a prominent factor responsible for incurring this
      additional risk. In this review we attempted to generate a consensus on the
      importance of BPV in the hypertension management and to evaluate different
      therapeutic options available to reduce BPV. Panel comprising of 11 leading
      experts from India in different areas of clinical practice (including nephrology,
      diabetes and endocrinology, cardiology, and critical care medicine) was convened.
      The board reviewed up to date literature on BPV, shared personal experiences from
      their clinical practice, and debated their opinions on the significance of BPV in
      hypertension management and also on various therapeutic options available to
      control it. The reviewers agreed that BPV is frequently observed in hypertensive
      individuals and it is a critical factor in hypertension management. Blood
      pressure variability can be measured by ambulatory blood pressure monitoring,
      home blood pressure monitoring, and office blood pressure monitoring. Members
      concurred that variations in blood pressure that are 10 standard deviations above
      the mean blood pressure should be considered as pathologically significant and
      such variations should be reduced using pharmacological therapies. The board
      opined that Angiotensin II Receptor Blockers,Calcium Channel Blockers etc such as
      Olmesartan, Nifedipine can be used to reduce BPV. As a way forward, the panel
      recommends to bridge the evidence gap that establishes a possible direct
      relationship between BPV and cardiovascular complications. Blood pressure
      variability has paramount role in the current hypertension management scenario.
      To reduce disease burden and increase quality of life of hypertensive
      individuals, physicians should consider lowering BPV along with physiological BP
      levels.

PMID- 29327528
TI  - MDCT Depiction of Spontaneous Rupture of Hepatic Hydatid Cyst with Peritoneal
      Hydatidosis.

PMID- 29327529
TI  - Unusual Empyema.

PMID- 29327530
TI  - Splenic Abscess Caused by Salmonella Typhi and Co-Infection with Leptospira.
AB  - Splenic abscesses caused by Salmonella typhi are a very rare complication of
      typhoid fever in this era of use of specific antibiotics. Co-infection with
      Leptospira in such a patient is even rarer. Clinical diagnosis of splenic abscess
      caused by Salmonella is difficult owing to its rarity, being insidious in onset
      and having nonspecific clinical presentation. Splenic abscesses are potentially
      fatal complication of typhoid fever. In most of these patients,
      hemoglobinopathies or some other underlying immunocompromised state is usually
      present. We report a case of splenic abscess, caused by Salmonella typhi, and co
      infection with Leptospira in a previously healthy young male.

PMID- 29327531
TI  - Isolated Pancreatic Tuberculosis in an Immunocompetent Host.
AB  - Despite the high prevalence of tuberculosis (TB) worldwide, pancreatic TB is
      rare. When present, pancreatic TB is frequently associated with miliary TB, often
      in immunocompromised hosts. Pancreatic TB may present as a pancreatic abscess,
      acute or chronic pancreatitis, and cystic or solid pancreatic masses. This is a
      case of isolated Tubecular infection of the pancreas in an immunocompetent
      patient, who presented with a discrete pancreatic abscess, and was subsequently
      diagnosed with isolated pancreatic TB. This case suggests that clinicians should
      have a heightened suspicion of pancreatic TB when faced with discrete pancreatic
      lesions, especially in patients from areas where the infection is endemic. Such
      recognition may lead to appropriate diagnostic testing, and possible resolution
      of pancreatic lesions with antitubercular therapy.

PMID- 29327532
TI  - Adrenal Oncocytoma - A Rare Functional Tumor Presenting as Cushing Syndrome.
AB  - Adrenal oncocytoma is very rare pathological variant of adrenal neoplasm. These
      are usually large and non-functional; however, rarely functional adrenal
      oncocytomas are also presented as Cushing's syndrome and pheochromocytoma. We
      report a case of adrenal oncocytoma in 38 year old female presented with symptoms
      of Cushing Syndrome.

PMID- 29327533
TI  - Post-transplant Lymphoproliferative Disorder.
AB  - Post-transplant lymphoproliferative disorders (PTLDs) are life-threatening
      complications of solid-organ transplantation and bone marrow transplantation
      leading to a high mortality. PTLD represents a heterogeneous group of
      lymphoproliferative diseases. They become clinically relevant because of the
      expansion of transplantation medicine together with the development of potent
      immunosuppressive drugs associated now with long survival. The risk of PTLD is
      highest in the early post-transplant period, but the cumulative risk increases
      with time. We report a case of two sequential malignancies - carcinoma bladder
      occurring -13 years and now gastric lymphoma -15 after renal transplantation in a
      73-year-old man.

PMID- 29327534
TI  - Gastric Angioinvasive Mucormycosis in Immunocompetent Adult, A Rare Occurrence.
AB  - Mucormycosis is a rare, opportunistic fungal infection that occurs almost
      exclusively in immunocompromised hosts such as patients with diabetes mellitus,
      leukemia, lymphoma, renal disease, septicemia, burns, malnutrition, and following
      long-term treatment with steroids and antibiotics. Based on the clinical
      presentation and involvement, mucormycosis is classified as six major forms,
      namely, rhinocerebral, pulmonary, cutaneous, gastrointestinal (GI), disseminated
      and miscellaneous, with rhinocerebral and pulmonary being the common forms. GI
      mucormycosis is rare, accounting for only 7% of all cases; however, the mortality
      rate is as high as 85%. Here we report a case of a young immunocompetent male who
      developed gastric invasive mucormycosis during an acute illness and succumbed to
      it despite all supportive care.

PMID- 29327536
TI  - Medical Symbols: Part-2.

PMID- 29327535
TI  - Catheter Assisted Management of Massive Pulmonary Embolism.
AB  - Pulmonary thromboembolism is common and missed by clinicians. We report a case of
      massive pulmonary embolism which was life threatening treated by the catheter
      assisted technique. Anticoagulation is the mainstay of therapy for most patients,
      with thrombolytic therapy reserved for some patients.1 Recent studies have
      suggested a role for systemic or catheter-directed thrombolytic therapy in
      selected patients.2 We present a case of a patient who presented with an PE, was
      successfully treated with catheter-directed thrombolysis.

PMID- 29327538
TI  - Angiotensin-converting Enzyme (ACE) Inhibitor Induced Macroglossia.

PMID- 29327537
TI  - Can Forced Expiratory Time be Used as a Supportive Tool in the Diagnosis of COPD
      ?

PMID- 29327539
TI  - [Surgical treatment of severe elbow injuries].

PMID- 29327540
TI  - [Analysis on the effect of surgical cleaning combined with external fixator for
      the treatment of post-traumatic heterotopic ossification of elbow joint].
AB  - OBJECTIVE: To evaluate the clinical efficacy of surgical treatment using a
      combined medial and lateral approach combined with an external fixator for the
      treatment of post-traumatic heterotopic ossification(HO) in patients with stiff
      elbow joints. METHODS: Surgical release using the combined medial and lateral
      approach combined with external fixation for the treatment of HO and elbow
      stiffness in 26 patients from July 2010 to December 2013. The study group
      included 18 males and 8 females, with an average age 38.7 years (ranged 14 to 60
      years). The time from injury to surgery averaged 9.3 (ranged 7 to 18) months.
      Before and after operation, the elbow range of motion and forearm rotation angle
      were measured, and the Mayo Elbow Performance Score (MEPS) was evaluated.
      RESULTS: The wound of all patients was well healed during the first period,
      except one patient who had chronic infection at the external fixation pin 3 weeks
      after operation. Then the external fixator was removed. All 26 patients were
      followed up, and the during ranged from 24 to 40 months, with an average of 34
      months. HO recurrence occurred in 1 patient 8 months after operation. The range
      of motion, forearm rotation angle, and Mayo Elbow Performance Score of elbow
      joint in patients was significantly improved compared with that before
      surgery(P<0.05). CONCLUSIONS: Surgical release using the combined medial and
      lateral approach combined with an external fixator for the treatment of traumatic
      HO and elbow stiffness can effectively improve elbow function, resulting in a
      satisfactory effect.

PMID- 29327541
TI  - [Mini-locking plates for the treatment of Regan-Morrey type III fracture of ulnar
      coronoid process through anterior approach of elbow joint].
AB  - OBJECTIVE: To explore clinical effects of mini-locking plates for the treatment
      of Regan-Morrey type III fractures of ulnar coronoid process through an anterior
      approach of elbow joint. METHODS: A retrospective analysis on 12 patients with
      Regan-Morrey type III fractures of the ulnar coronoid process was performed from
      January 2011 to June 2014, who were treated with unini-locking plates through the
      anterior approach of elbow joint. There were 7 males and 5 females, ranging in
      age from 23 to 65 years old, averaged 43 years old. Four patients had fractures
      on the left and 8 patients had fractures on the right. The X-ray films were taken
      to evaluate the location and healing of the fracture before and after operation.
      Clinical evaluation included analysis on surgical complications, range of motion
      and Mayo elbow function score. All the patients were treated with mini-locking
      plates, and the elbow joint was stable after operation. RESULTS: All the patients
      were followed up, and the duration ranged from 14 to 36 months. All the fractures
      were healed, and the healing time ranged from 12 to 20 weeks. The average healing
      time was 15.6 weeks. There were no complications occurred such as heterotopic
      ossification, traumatic arthritis and others. At the latest follow-up, the
      average angle of elbow flexion was (127.0+/-5.6) degrees (120 degrees  to 135
      degrees ); the average extension angle was(4.2+/-4.5) degrees  (0 degrees  to 10
      degrees ); the average pronation angle of forearm was (86.0+/-6.1) degrees (75
      degrees  to 90 degrees ); the average supination angle of forearm was (87.0+/
      6.9) degrees (80 degrees  to 100 degrees ). Mayo elbow function score was 80 to
      96 points, with an average of 88 points, of which 2 cases got an excellent
      result, 10 good. CONCLUSIONS: Elbow anterior approach can clearly expose the
      Regan-Morrey type III coronoid fractures, and mini-locking plate fixation has a
      satisfactory effect.

PMID- 29327542
TI  - [Treatment of coronal shear fracture of the distal end of the humerus by the
      olecranon osteotomy approach].
AB  - OBJECTIVE: To explore the effectiveness of olecranon osteotomy approach for the
      treatment of coronal shear fracture of the distal end of the humerus. METHODS: A
      retrospective analysis was made on the clinical data of 34 patients with the
      coronal shear fracture of the distal end of the humerus treated by the olecranon
      osteotomy approach from January 2005 to January 2013. Of 34 cases, there were 15
      boys and 19 girls, aged from 17 years to 84 years (mean, 54.9+/-10.2 years); 18
      patients had fractures on the left and 16 patients had fractures on the right.
      Fractures were classified according to the Bryan and Morrey classification united
      Mckee classification: type Iinjuries occurred in 10 cases, type IIinjuries in 5
      cases, type III injuries in 10 cases and type IV injuries in 9 cases. The Mayo
      elbow functional scores were evaluated for analysis. RESULTS: All the patients
      were followed up, and the duration ranged from 15 to 96 months, with a mean of
      (35.1+/-7.2) months. Average arc of motion was (132.1+/-11.2) degrees  in flexion
      and (4.6+/-1.9) degrees  in extension. The average Mayo score was 85.9+/-6.3(73
      to 94 scores). Thirteen patients got an excellent result, 15 good and 6 poor. The
      average Mayo score was 88.6+/-3.7 in type Iinjuries, 85.8+/-4.6 in type
      IIinjuries, 81.8+/-5.8 in type III injuries and 87.5+/-9.1 in type IV injuries.
      There were no significant differences in outcomes. CONCLUSIONS: The treatment for
      the coronal shear fracture of the distal end of the humerus by the olecranon
      osteotomy approach can achieve the satisfactory curative effect, maintain the
      reduction and improve the elbow function.

PMID- 29327543
TI  - [Management of displaced radial neck fractures in children: elastic stable
      intramedullary nailing vs K-wire fixation].
AB  - OBJECTIVE: To compare the complications and clinical outcome of titanium elastic
      nail(TEN) versus K-wire fixation(KW) for the treatment of displaced radial neck
      fractures in children. METHODS: From January 2009 to December 2014, 56 children
      with displaced radial neck fractures were studied retrospectively according to
      the inclusion criteria. Based on the different methods of internal fixation,
      patients were divided into two groups: titanium elastic nail (TEN group) and K
      wire fixation (KW group). Among 25 patients(15 males and 11 females, aged from 3
      to 12 years old with an average of 8.6+/-2.1) treated with TEN, 16 patients had
      type III fractures, 19 patients had type IV fractures according to Metaizeau
      Judet modified classification; 20 patients were treated with closed reduction and
      5 patients were treated with open reduction; the time from injury to treatment
      ranged from 1 to 8 days with an average of (3.6+/-1.7) days. Among 31 patients
      (20 males and 11 females, aged from 3 to 11 years old with an average of 9.1+/
      1.9 years old) treated with KW, 19 patients had type III fractures, 12 patients
      had type IV fractures; 22 patients were treated with closed reduction, and 9
      patients were treated with open reduction; the time from injury to treatment
      ranged from 2 to 7 days with an average of (3.7+/-1.5) days. No significant
      differences between two groups were found in general data. Operative time,
      hospitalization time, healing time of fracture, internal fixation time,
      postoperative complications and function recovery of the two groups were compared
      and evaluated. RESULTS: The average follow-up period of the patients was 22.1
      months in TEN group(ranged, 16 to 48 months), and 21.9 months in KW group(ranged,
      13 to 48 months). There were no significant differences between these 2 groups in
      follow-up duration, average hospitalization time and fracture healing time. The
      operation time, hospital costs and internal fixation time in TEN group were
      (56.6+/-11.8) min, (18 000+/-3 000) Yuan(RMB), (9.1+/-2.5) weeks respectively;
      and in KW group were(45.5+/-10.3) min, (8 000+/-1 000) Yuan(RMB), (4.8+/-1.6)
      weeks respectively, there were significant differences between two
      groups(P<0.05). Outcome scores according to Metaizeau and Tibone-Stoltz had no
      significant differences between two groups(P>0.05). CONCLUSIONS: There is no
      significant difference of therapeutic effects between TEN and KW for children
      with displaced radial neck fractures. Because the removal of TEN fixation
      requires the secondary anesthesia, and the TEN costs significantly more than KW,
      TEN still can't replace the traditional KW for the treatment of radial neck
      fracture in children.

PMID- 29327544
TI  - [Clinical outcome of arthroscopic anterior cruciate ligament remnant-preserving
      reconstruction].
AB  - OBJECTIVE: To evaluate the clinical outcome of arthroscopic anterior cruciate
      ligament(ACL)reconstruction with remnant cuff preservation. METHODS: There were
      42 cases of ACL tear were performed reconstruction in our department from January
      2012 to December 2014. The patients were 28.4 years old on average, 17 males and
      25 females. ACL reconstruction was performed under arthroscopy with remnant cuff
      preservation. The stability of knee was assessed by Lachman test and anterior
      drawer test. The function of knee was assessed through Lysholm score and Tegner
      activity rating. MRI of the knee was checked 12 months postoperatively. RESULTS:
      The stability tests of all patients were negative postoperatively. Lysholm score
      of all patients 12 months after operation was 96.8+/-6.1, which was significantly
      better than 37.8+/-7.1 of preoperatively. Tegner activity rating of all patients
      12 months after operation was 6.2+/-0.9, which was significantly better than
      2.1+/-0.4 of preoperatively. It showed the grafts were very well in MRI 12 months
      after operation. CONCLUSIONS: Arthroscopic anterior cruciate ligament remnant
      preserving reconstruction could restore the stability of knee.

PMID- 29327545
TI  - [Study on therapeutic effects of arthroscopic repair on medial patellar
      retinaculum acute injury].
AB  - OBJECTIVE: To accurately define the injury position of medial patellar
      retinaculum with acute injury under the guiding of high frequency
      ultrasonography, and to study therapeutic effects of suture operation on medial
      patellar retinaculum in the injuried position. METHODS: From June 2009 to March
      2014, there were 17 patients with acute patellar dislocation, 6 males and 11
      females with average age of (16.2+/-6.2) years old. The duration time of patellar
      dislocation was 2 weeks. Before operation, the medial patellar retinaculum of all
      patients were examined with the high frequency ultrasonography, and the skin with
      the non-continuous fiber was iudicated as the surface mark under the high
      frequency ultrasonography. The injury position of medial retinaculum was in the
      middle of 5 patients who were treated with suture operation of arthroscopic
      medial retinaculum. The injury position was in the patellar edge in 12 patients
      who were treated with fixing bone anchor on patella and arthroscopic suture
      operation of medial retinaculum. The CT examination and Kujala scores, patellar
      tilt angle on CT film, measured maximal angles of passive or active knee flexion
      and apprehension test were observed before treatment and postoperative 18 months.
      RESULTS: Eighteen months after treatment, Kujala scores were 92.2+/-11.1 and
      patellar tilt angle were(11.5+/-4.2)  degrees , and there was no statistical
      difference between post-operation and pre-operation. The difference between
      maximal angles of passive knee flexion(133.5+/-4.2)  degrees  and normal had no
      statistically significance. Maximal angles of active knee flexion were(153.5+/
      4.6)  degrees . Ultrasonography showed the continuous fiber of medial
      retinaculum. A patient showed positive apprehension test and no patient had the
      recurrence patella instability after operation. CONCLUSIONS: The injury position
      of medial patellar retinaculum was accurately shown by high frequency
      ultrasonography and treated with arthroscopic suture operation. Knee
      immobilization time after operation was shorten. Eighteen months after operation,
      knee joint function was good, and no patient had the recurrence patella
      instability.

PMID- 29327546
TI  - [Bone mineral density decreased is a high risk factor for uncemented acetabular
      cups migration in female total hip arthroplasty patients].
AB  - OBJECTIVE: To investigate the decrease of bone mineral density in female
      patients, effects on acetabular displacement. METHODS: From October 2013 to
      November 2015, a total of 34 patients underwent total hip replacement in the
      Department of orthopedics, the Third Affiliated Hospital of Zunyi Medical
      College. The two groups of patients were female and the patients were treated
      with hip osteoarthritis. Based on the lowest value of preoperative dual energy X
      ray bone mineral density (DXA), the patients were divided into normal group and
      low bone mineral density(-3.5<=T<=-1). There were 10 patients in the normal
      group, ranging in age from 55 to 64 years old, with an average of (58.00+/-4.22)
      years old. There were 24 patients in the low bone density group, ranging in age
      from 58 to 72 years old, with an average age of (65.71+/-8.19) years old. All the
      patients received a THA implant with ceramic-on-ceramic bearings(Depuy America).
      The lining system was Pinnacle cup. During the operation, the acetabular cup was
      maintained at abduction 45 degree and anteversion 15 degree. Analysis (RSA) of
      acetabular components in 3, 6, 12, and 24 months after surgery. RESULTS: There
      was a statistically significant difference in cup migration between patients with
      normal BMD and those with low BMD. At 3 months, compare to the normal group, the
      low bone mineral density (BMD) occurred in the X axis (95% confidence interval,
      0.01 to 0.31; P=0.006) and Y (95% confidence interval 0.20 to 0.39; P=0.003). The
      initial rotation occurs in a separate Z axis(95% confidence interval -0.26 to
      0.81; P=0.006). CONCLUSIONS: It has produced that increaseed migration of
      uncemented cups in female patients with low systemic BMD in 3 months after
      surgery.

PMID- 29327547
TI  - [Finite element analysis on the effect of lateral wedge insole intervention on
      the contact characteristics of the subtalar joint].
AB  - OBJECTIVE: To establish a three-dimensional finite element model of the lower
      limb bones, and investigate the changes of the contact characteristics of the
      subtalar joint after using laterally wedge insole intervention. METHODS: Using
      the reverse modeling technology, the lower limb bones of normal adult volunteers
      was scanned by CT. Mimics 10.0 and Geomagic Studio 6.0 software were used to
      reconstruct the 3D morphology of bones and external soft tissue of the feet. The
      laterally wedge insole was designed in ProE 5.0. And then all the models were
      imported into Hyperwork 10.0 and meshed, and given the material properties. The
      finite element analysis was carried out in ABAQUS 6.9. RESULTS: A three
      dimensional finite element model of the lower extremity was established, which
      was consisted of 95 365 nodes and 246 238 elements. The contact area of the
      standing state of the lower joint was larger than that of the anterior middle
      joint surface. The peak stress was concentrated in the anterior lateral part of
      the posterior articular surface, and the average stress value was(3.85+/-1.03)
      MPa. Compared with the model of 0 degrees , the contact area of the subtalar
      joint was reduced accordingly. There was a significant correlation between
      anterior middle joint |r|=0.964, P=0.008, and posterior articular |r|=0.978,
      P=0.002. The equivalent stress of 0 degrees  model distributed from(3.07+/-1.14)
      MPa to(3.85+/- 1.03) MPa, which had no statistically difference. Compared with
      the 0 degrees  model, the equivalent stress of the anterior and middle joint
      surfaces of the 8 degrees  model was significantly reduced(P<0.05), but the peak
      stress of the posterior articular surface was significantly increased(P<0.05). In
      the 12 degrees  model, the peak stress was sharply increased to(10.51+/-3.53)
      MPa. Compared with 8 degrees  model, there was no statistically
      difference(P<0.05). Although the peak stress was slightly increased in 16 degrees
      model, but compared with 12 degrees  model, there was no statistically
      differences(P>0.05). CONCLUSIONS: Although a certain valgus can be obtained in
      subtalar by wearing LWI, the result comes at the cost of the stress concentration
      on posterior surface. Through this study, we can find that LWI with 8 degrees 
      tilt angle could provide appropriate valgus moment without causing excessive
      concentration. Therefore, in order to avoid secondary ankle complications, we
      should not increase the tilt angle blindly.

PMID- 29327548
TI  - [Research of TCM synthetic rehabilitation on the recovery of wrist joint after
      distal radius fractures].
AB  - OBJECTIVE: To evaluate efficacy and advantages of the Traditional Chinese
      Medicine (TCM) synthetic rehabilitation therapy in the treatment of wrist
      dysfunction after distal radius fractures. METHODS: From May 2014 to October
      2015, 72 patients with distal radius fracture meeting standards were treated
      using central randomization system for clinical research. All the patients were
      divided into two groups: 36 patients in test group and 36 in control group. Sixty
      nine cases were finished treatment and followed up in the end. The test group
      fell off 1 case, and the control group fell off 2 cases. The test group was given
      TCM synthetic rehabilitation (manipulative therapy, joint mobilization, soaking
      washing with Chinese medicinal herbs, functional exercise), and the control group
      was given functional exercise as well as soaking-washing with Chinese medicinal
      herbs, 3 weeks for both. Five evaluation standards were used in this research,
      which were grip strength, patient-rated wrist evaluation (PRWE), Gartland and
      Werley wrist score, self-rating anxiety scale(SAS) and the overall curative
      effect evaluation. Before treatment(baseline), after 3 weeks of treatment and 3
      months after fracture were the three points in time when collected the data.
      RESULTS: After 3 weeks of treatment and 3 months after fracture, the test group
      had a significantly better results than those of control group in the PRWE, G-W
      wrist score and the overall curative effect evaluation(P<0.05). In terms of grip
      strength recovery, after 3 weeks of treatment, the intergroup difference between
      the test group and the control group were statistically significant relative to
      the baseline regarding grip strength of ipsilateral wrist by group t
      test(P<0.05). However, the test group and the control group had no statistically
      significant relative to the baseline at 3 months after fracture in grip
      strength(P<0.05). For the anxiety of patients, compared with the test group and
      control group at before and after rehabilitation treatment, the anxiety of both
      test group and control group cases was eased(P<0.05). However, The degree of
      anxiety relief in test group and control group cases had no difference(P>0.05).
      CONCLUSIONS: The TCM synthetic rehabilitation therapy has better curative effects
      on the treatment of functional disability of wrist joints after distal radius
      fractures than the general therapy of soaking-washing with Chinese medicinal
      herbs and functional exercise.

PMID- 29327549
TI  - [Characteristics and treatments of the Essex-Lopresti injury].
AB  - OBJECTIVE: To summarize experiences of operative treatment for Essex-Lopresti
      injury, and analyze the effect of the compare repair of interosseous membrane of
      forearm(IOM)on the forearm function. METHODS: Twenty-four patients of Essex
      Lopresti injury were treated from January 2005 to December 2013, 16
      patients(group A) with radius and/or ulna fractures were treated with open
      reduction and internal fixation of radius or ulna and repair of forearm bone
      membrane at the same time, and then treated with open reduction and internal
      fixation of head of radius, as well as lower ulnar joint fixation or repair of
      wrist triangle fiber complex. Another 8 patients without radius and or ulna
      fractures(group B) were treated with open reduction and internal fixation of head
      of radius, as well as lower ulnar joint fixation or repair of wrist triangle
      fiber complex. The wrist joint function was evaluated using Cooney wrist
      functional rating index, and the elbow joint function was evaluated using Mayo
      elbow-performance score 2 weeks and 2 years after operation. RESULTS: According
      to Cooney wrist functional rating index, 4 patients in group A got a fair result
      and 12 poor, 2 patients in group B got a fair result and 6 poor 2 weeks after
      operation; 8 patients in group A got a good result, 6 fair and 2 poor, 5 patients
      in group B got a good result, 2 fair and 1 poor 2 years after operation.
      According to Mayo elbow-performance score, 2 patients in group A got a good
      result, fair and 6 poor, 1 patient in group B got a good result, 5 fair and 2
      poor 2 weeks after operation; 8 patients in group A got a good result, 6 fair and
      2 poor, 4 patients in group B got a good result, 3 fair and 1 poor. There were no
      statistically differences between two groups 2 weeks and 2 years after operation.
      CONCLUSIONS: It is important to restore the length of radius and/or ulna and
      maintain the dynamic stabilization of elbow and wrist for treat Essex-Lopresti
      injury. The repair of IOM has no effect on the forearm function.

PMID- 29327550
TI  - [Study on the correlative factors of the pain under the second metatarsal in
      patients with hallux valgus].
AB  - OBJECTIVE: To analyze the correlation between the hallux valgus angle and arch X
      ray parameters change, plantar pressure by measuring the X-ray indexes and foot
      pressure indexes in patients with hallux valgus, as well as to study the main
      cause factors for the pain under the second metatarsal head. METHODS: A
      retrospective study of 254 patients(477 feet) treated in Wangjing Hospital from
      January 2012 to June 2013 was performed. The pain under the second metatarsal
      head and age distribution were recorded. All the patients were divided into two
      groups according to the second plantar bone pain: pain group and no pain group.
      The following indexes were measured and compared: HAVA(hallux abductor valgus
      angle), IMA1-2(the inter-metatarsal angle between the first and second
      metatarsals), IMA1-5(the inter-metatarsal angle between the first and fifth
      metatarsals), TAOTMLA (top angle of the medial longitudinal arch), AAOTMLA
      (anterior angle of the medial longitudinal arch), SMRL (the second metatarsal
      relative length than the first), and the plantar pressure indicators including
      TPUM (touch the ground time percentage under the second metatarsal head), PPUM
      (peak pressure under the second metatarsal head), and IUM(impulse under the
      second metatarsal head). All the factors were evaluated by Logistic regression
      analysis. RESULTS: Spearman rank correlation test showed that there were
      statistical significance in correlation between HAVA and IMA1-2, IMA1-5, TAOTMLA,
      AAOTMLA, TPUM(P<0.05, r=0.647, 0.553, 0.127, -0.165, 0.158). Factors including
      the HAVA, SMRL and the TPUM were the risks for the pain under the second
      metatarsal head in patients with hallux valgus(P<0.05, ORj=1.030, 1.069, 1.060).
      CONCLUSIONS: Increase of the hallux valgus angle causes the collapse of hallux
      valgus arch, extending the weight bearing time of the second metatarsal and
      increasing the possibility of the pain under the second metatarsal.

PMID- 29327551
TI  - [Analysis of the axial stretching force of the small splint fixation system].
AB  - OBJECTIVE: To measure the axial stretching force produced by the small splint
      fixation system in the treatment of the fracture. METHODS: Dumbbell shaped
      plexiglass was machined to model the bone shaft with expanded two ends. Force
      transducer was set at the model fracture site to measure the stretching force
      produced by fracture fixation of the small splint with cloth aqueous bag that
      simulated the muscles and other soft tissue underneath. RESULTS: There was
      positive relationship between the axial stretching force produced at the model
      fracture site and the transverse pressing force exerted by the external plates.
      The ratio of which was 1/10. CONCLUSIONS: Muscle enwrapped with fascia is similar
      to the cloth aqueous bag system in mechanical structure. From this article, axial
      stretching force exists at the bone shaft fracture site when fixed by small
      splint which exerts the force transversely from the outside of the extrimity.

PMID- 29327552
TI  - [Treatment of irreducible Gartland typeIII humerus supracondylar fracture in
      children with limited open reduction and percutaneous K-wire internal fixation].
AB  - OBJECTIVE: To investigate the clinical outcomes of limited open reduction and
      percutaneous K-wire internal fixation for the treatment of irreducible Gartland
      type III humerus supracondylar fracture in children. METHODS: From May 2006 to
      October 2014, 132 patients with irreducible Gartland type III humerus
      supracondylar fracture were treated with reduction and percutaneous K-wire
      internal fixation. The reduction was performed with the guiding of surgeon's
      finger, and the lateral approach with periosteum torn was chosen according to the
      shift direction of the distal fractures. Among them, there were 82 males and 50
      females with an average age of 5.8 years old(ranged from 2 to 14 years old).
      RESULTS: All the patients were followed up, the duration ranged from 6 to 36
      months, with an average of 13.7 months. Ninety-five patients got an excellent
      result, 27 good, 8 fair, and 2 poor. CONCLUSIONS: Limited open reduction and
      percutaneous K-wire internal fixation for the treatment of irreducible Gartland
      type III humerus supracondylar fracture in children has many advantages: simple
      manipulate, not affected by the elbow swelling, and satisfactory curative effect.
      It is worth popularizing in clinic.

PMID- 29327553
TI  - [Preliminary development of drill template-assisted placement of reverse
      intramedullary lag screw for superior ramus of pubis using three dimentional
      print technique].
AB  - OBJECTIVE: To investigate the feasibility of a drill template for the placement
      of reverse intramedullary lag screws on the outside of the pubis based on digital
      design and 3D printing technology. METHODS: The preoperative CT images of a 23
      year-old male patient with pelvic fracture were collected retrospectively.
      According to the Young and Burgess classification, the type of pelvic fracture
      was LC IIwith the 3D printing technology. The data was reconstructed by 3D
      imaging reconstruction software to produce 1:1 three dimensional model. The screw
      channel and the individual drill template was designed by the softwares of Mimics
      10.01 and Geomagic 12, the accuracy of a drill template was observed by X-rays
      and CT scans after the placement of 2.0 mm K-wires in the three dimensional
      template fixed on the model. RESULTS: Three dimensional pelvic model and digital,
      individual drill template could meet the requirement of the placement of reverse
      interamodullary lay screw for the treatment of superior ramus of pubis fracture.
      K-wire was placed and the accuracy of screw placement was confirmed using the X
      ray and CT scanning. Template and the corresponding anatomical landmark fitted
      well. CONCLUSIONS: With the assistance of the individual design and 3D printing
      technology, the accurate placement of superior ramus of pubis fracture screws can
      be realized. This technology is helpful to reduce the operation time and X-ray
      exposure of the patients and doctors.

PMID- 29327554
TI  - [Ewing's sarcoma misdiagnosed as nonossifying fibroma: a case report].

PMID- 29327555
TI  - [Anterior versus posterior approach for multilevel cervical spondylotic
      myelopathy: a meta-analysis].
AB  - OBJECTIVE: To assess the clinical effectiveness and safety of anterior versus
      posterior approach for multilevel cervical spondylotic myelopathy. METHODS: The
      following databases were searched: the Cochrane Library, PubMed, EM base, OVID,
      CBM, Wanfang Data, CNKI. Relevant journals were manually searched for randomized
      controlled trials or clinical controlled trials(CCTs) that investigated the
      clinical effectiveness and safety of anterior and posterior approach for
      multilevel cervical spondylotic myelopathy. Two reviewers independently screened
      the literature according to inclusion and exclusion criteria, extracted the data,
      and assessed the methodological quality of included studies. Meta-analysis was
      performed by using RevMan 5.2 software. RESULTS: Eight CCTs, involving 1 151
      patients, were included. Significant differences were found between anterior and
      posterior approach with respect to complications, OR=2.19, 95%CI (1.50, 3.19),
      P<0. 000 1; and neural recovery rate, WMD=11.04, 95% CI(0.60, 21.47), P=0.04 . In
      addition, there were no significant differences in preoperative JOA scores,
      WMD=0.13, 95% CI (-0.20, 0.46), P=0. 44; postoperative JOA scores, WMD=0.45, 95%
      CI (-0.10, 1.00), P=0.11; operation time, WMD=39.43, 95% CI(-5.92, 84.78),
      P=0.09; and amount of intraoperative bleeding, WMD=5.46, 95% CI(-96.65, 107.58),
      P=0. 92). CONCLUSIONS: There are no significant differences between anterior and
      posterior approach for multilevel cervical spondylotic myelopathy in the recovery
      of neural function of the spinal cord, operation time and intraoperative
      bleeding. However, posterior appreach showed fewer complications than anterior
      appreach.

PMID- 29327556
TI  - [Surgical treatment for the fractures and dislocations of the elbow in old
      patients].
AB  - OBJECTIVE: To introduce and report the preliminary results of 7 old patients with
      fractures and dislocations of the elbow. METHODS: From July 2011 to August 2015,
      7 old patients suffered from fractures and dislocations of the elbow(5 of which
      were terrible triad). One patient had type Iradial head fracture, 3 type IIand 1
      type III according to the Mason classification, and 1 type I, 5 type IIand 1 type
      III according to the Regan-Morrey classification. All the 7 patients received
      operation and then were treated with external fixation. Fractures of the radial
      head were fixed with Herbert screws or locking plates and screws. Fractures of
      ulnar coronoid were reduced and fixed with lag screws or K-wires or PDS sutures
      or locking screws according to the types. The lateral and medial collateral
      ligaments were also repaired. Plaster external fixation was applied for 3 weeks
      after operation, in the position with elbow flexion in 90 degrees and forearm
      rotation in neutral. External fixation braces were used for each patient after
      the plasters were removed, and at the same time rehabilitation programs were
      carried out. RESULTS: All the 7 patients were followed up, and the during ranged
      from 13 to 48 months(averaged, 20 months), with healed fractures, stable elbow
      and no pain movement. The functional outcome was excellent in 3 patients, good in
      3 and fair in 1 according to the Mayo Elbow Performance Score(MEPS). CONCLUSIONS:
      It is not easy to get stable fixation for fractures and dislocations of the elbow
      in old patients with osteoporosis and low density of bone, but the operation can
      achieve satisfied clinical outcomes after external fixation.

PMID- 29327557
TI  - [Surgical treatment for 14 patients with old fractures of humeral lateral condyle
      in children].
AB  - OBJECTIVE: To study clinical effects of operation for the treatment of old
      fractures of the humerus lateral condyle in children. METHODS: From January 2012
      to January 2014 in our department, 14 children of old humeral lateral condyle
      fractures were treated with operation. Ten cases were male, 4 cases were female;
      age from 2 to 12 years old, average 5.8 years old. The initial diagnosis was type
      IIfracture according to the Milch ciassification, the loss of treatment in 11
      cases, conservative treatment in 3 cases of nonunion after fracture displacement.
      Two cases had mild cubitus valgus deformity; 10 cases had elbow disorders, and
      the motion range was limited from 15 degrees  to 60 degrees ; 6 cases had pain in
      activity. The time from injury to operation was 32 to 176 days(62 days on
      average) in 14 cases, the 14 cases were treated with open reduction and internal
      fixation. According to the Modified An-Morrey elbow function assessment criteria
      after surgery for curative effect. RESULTS: Fourteen cases were followed up for 1
      to 3 years, average 1.8 years. No nonunion, malunion, aseptic necrosis of the
      epiphysis, cubitus varus or valgus occurred. Five cases had mild protrusion
      deformity of external condyle, 3 cases still had mild dysfunction. The time of
      clinical bone union was 4 to 8 weeks in X-ray films. Five cases had bony spur
      formation, 3 cases had signs of early closure of epiphysis; 2 cases had a
      increasing volume of humeral lateral condyle; and 2 cases appeared tail
      deformity. Modified An-Morrey score averaged(95.2+/-3.6) points, 13 excellent, 1
      good. CONCLUSIONS: For the old fracture of humeral lateral condyle, operation can
      effectively restore the appearance and function of elbow joint, and the short
      term curative effect is satisfactory, but the long-term effect needs further
      observation.

PMID- 29327558
TI  - [Modified osteotomy of olecranon for the management of inter-condylar fracture of
      the humerus].
AB  - OBJECTIVE: To explore the surgical method and clinical outcome of modified
      osteotomy of olecranon for the treatment of inter-condylar fracture of humerus.
      METHODS: From May 2007 to December 2012, 32 patients of intercondylar fracture of
      humerus were treated surgically through the approach of modified osteotomy of
      olecranon. The patients were 21 males and 11 females with a mean age of 46.3
      years (ranged 18 to 65 years). Nineteen fractures occurred on the right extremity
      and 13 on the left extremity. According to the AO classification, type C1
      fracture was found in 7, C2 in 11 and C3 in 14. Five patients suffered from open
      fracture (Gustilo type Iin 3, type II in 2). Other fractures occurred in 6
      patients and the primary injury of nerve occurred 6. The healing of the osteotomy
      was evaluated with physical examination and plain X-ray film, and the function of
      elbow was assessed according to Cassebaum scale. RESULTS: All the patients were
      followed from 9 months to 5 years(average, 1.9 years). All the osteotomies healed
      at 7.4 weeks averagely after operation, and no nonunion, delayed union, fracture
      of ulna olecranon were found. Two cases had little pain on the elbow, heterotopic
      ossification occurred in 2 cases and cutting bone block loosed in 1 case. The
      function of the elbow showed excellent in 19 cases, good in 8, fair in 4 and poor
      in 1. CONCLUSIONS: The use of the approach of modified olecranon osteotomy for
      surgical management of intercondylar fracture of humerus has some advantages, it
      provides satisfactory stability with simple technical procedures avoiding inter
      articular invasion, and it facilitates rehabilitation exercises and providing
      good results with low complication rates.

PMID- 29327560
TI  - [Research progress on reatment of unstable atlas fracture with single-segment
      fixation by transoral approach].
AB  - As a common type of fracture in cervical, atlas fracture is frequently unstable
      due to its special anatomical structure. In a previous treatment, external
      fixation was likely to bring low bony union rate and long-term neck pain, while
      occipito-cervical fusion and atlantoaxial fusion sacrifice range of motion in
      cervical spine. Reduction and single section fixation of atlas by anterior
      lateral mass screws through the transoral approach were reported by some
      scholars, and the retrospective study demonstrated the high healing rate,
      reservation of cervical ROM and less bleeding. But it also has high risks of
      cervical spinal cord and vertebral artery damage, as well as the post-operation
      infection. Moreover, the indication and fixation strength require further
      evidences. As a result, this surgical option provides a new way for spinal
      surgeons to deal with unstable atlas fractures.

PMID- 29327559
TI  - [Combined surgical approaches in the treatment of complex tibial plateau
      fractures].
AB  - OBJECTIVE: To explore the early clinical efficacy of a posteromedial inverted "L"
      shape approach combined an assisted antero lateral assisted approach for the
      treatment of complex fractures of tibial plateau. METHODS: From March 2011 to
      June 2014, the posteromedial inverted "L" shape approach combined with the antero
      lateral assisted approach in the treatment of Schatzker type IV, V, VI tibial
      plateau fracture were performed in 34 cases. There were 23 males and 11 females,
      ranging in age from18 to 67 years old, averaged 34.9 years old; 19 patients had
      fractures on the left and 15 patients had fractures on the right. According to
      Schatzker classification, 11 cases of type IV, 15 cases of type V and 8 cases of
      type VI. According to the three column classification, 23 cases of double column
      fractures, 11 cases of three column fractures. The X-ray healing time and knee
      joint mobility were recorded. The mean tibial plateau angle(TPA) and the mean
      posterior slope angle (PA) were measured and recorded immediately after
      operation, 6 and 12 months after operation. The knee function was evaluated using
      the Hospital for Special Surgery Score(HSS) 3, 6 and 12 months after operation.
      RESULTS: Among all the patients, 28 patients were followed up, and the duration
      time ranged from 8 to 39 months with a mean of(21.6+/-8.7) months. All the
      fractures were healed. The healing time in terms of X-ray ranged from 12 to 24
      weeks, with a mean of (14.5+/-3.6) weeks. The range of knee activity ranged from
      105 degrees  to 135 degrees , with a mean of (121.5+/-5.5) degrees . Immediately
      after operation, 6 and 12 months after operation, the mean tibial plateau angle
      (TPA) was (84.3+/-1.8) degrees , (85.1+/-1.3) degrees , (85.6+/-1.6) degrees ,
      and the mean posterior slope angle (PA) was (7.8+/-1.6) degrees , (7.8+/-1.3)
      degrees , (7.7+/-2.3) degrees , respectively, showing no significant difference
      between the 3 time points. The mean HSS score at 3, 6 and 12 months after
      operation was 71.4+/-1.4, 76.7+/-1.7, 81.6+/-1.2 respectively, showing no
      significant differences between the 3 time points. One patient with early knee
      joint stiffness had 6 degrees  of the restricted straight range after the active
      functional exercise, 1 year after operation. Anterolateral wound dehiscence
      occurred in 1 cases but was cured by dressing without deep wound infection
      occurred. The pain occurred in 4 cases when the weather changed. At the end of
      follow-up, no case of knee joint instability, knee valgus, loosening or breakage
      occurred. CONCLUSIONS: The posteromedial inverted "L" shape approach combined
      assisted anterior lateral approach for the treatment of complex fractures of
      tibial plateau can expose the operation area, repair the fracture under the
      direct vision, and implant a full amount of bone graft for the collapse of the
      platform.Thus, the smoothness of the articular surface is restored, and the
      fixation is firm, which is beneficial to the early functional exercise, less
      complications, and satisfactory clinical curative effects.

PMID- 29327561
TI  - Hostility of proximal aortic neck anatomy in relation to abdominal aortic
      aneurysm size and its impact on the outcome of endovascular repair with the new
      generation endografts.
AB  - BACKGROUND: To assess the relation of abdominal aortic aneurysm (AAA) diameter
      with the proximal neck anatomy (PNA) hostility and to evaluate its impact on the
      endovascular aneurysm repair (EVAR) outcomes with the use of newer generation
      endografts. METHODS: Retrospective analysis of single institution's recorded data
      from February 2009 to April 2016. Patients' characteristics, co-morbidities,
      aortic morphology, perioperative characteristics and outcomes were analyzed. In
      relation to AAA diameter 2 groups were identified: group A (50 - 55mm) and group
      B ( >55mm). Hostile PNA was defined based on: neck diameter >28mm, length <15mm,
      angulation >60o, and circumferential thrombus and/or calcification >50%. The
      aortic neck scoring system was calculated. Multiple logistic regression analysis
      with a forward likelihood ratio method adjusted for age and gender was
      undertaken. RESULTS: 317 patients (96% males, mean age 72.4+/- 9 years, 80%
      elective) were follow up for a mean of 23.4 months (range, 3-86 months). No
      differences were observed in demographics and co-morbidities between the two
      groups (group A:134, 42% vs. group B: 183, 58%). Hostile PNA was present in
      147/317 (46%) patients and significantly more likely to be present in group B
      (P<.001). In group B the aortic neck score was higher (P<.001), the likelihood
      for having hostile PNA increased for neck diameter by 2.2 -fold (OR 2.2, P=.013,
      95% CI: 1.18-4.03), length by 2.3-fold (OR 2.3, P=.012, 95% CI:1.20-4.51), angle
      by 4.8-fold (OR 4.8, P= .002, 95% CI:1.79-13.24) and presence of thrombus by 1.5
      fold (OR 1.5, P=.037, 95% CI: 1.45- 10.34). No association existed for neck
      calcification (P=.071). Technical success, adjunctive procedures, perioperative
      characteristics and outcomes were comparable in friendly and hostile PNAs.
      CONCLUSIONS: PNA hostility is more likely in AAA with diameter >55mm but with the
      use of newer generation endografts this did not influence the short- and mid-
      term EVAR outcomes. Longer follow-up is needed for a more definite conclusion.

PMID- 29327562
TI  - Development of a porcine beating-heart model of self-myocardial retroperfusion:
      evaluation of hemodynamic and cardiac responses to ischemia and clinical
      applications.
AB  - BACKGROUND: Retrograde perfusion into the coronary sinus is used to deliver
      cardioplegia. We developed an in-vivo porcine beating-heart model of self
      myocardial retroperfusion (SMR) using the venous route to supply myocardial
      oxygenation and sought to assess hemodynamic and cardiac responses triggered by
      SMR before and after a prolonged occlusion of the LAD. METHODS: A bypass-line
      between the ascending aorta and the coronary sinus was made to perform a
      selective retrograde perfusion of the great cardiac vein with oxygenated blood
      (SMR). A Control group (N.=6) was assigned to collect baseline data, and an SMR
      group (N.=6) was dedicated to undergo SMR with occlusion of LAD for 240 minutes.
      Cardiac output (CO), maximal pressure in the LV (Pmax in-LV), stroke volume (SV),
      left ventricular ejection fraction (LVEF), diastolic durations, heart rate, and
      arterial systemic pressure were evaluated with conductance catheters for the
      following periods: basal (before SMR), SMR with patent LAD, and SMR with occluded
      LAD. In order to assess peripheral perfusion, patterns of sublingual
      microcirculation were analyzed. At the end of the procedures, the hearts were
      harvested for histology. RESULTS: Echographic LVEF evaluation was affected by
      sternotomy, but conductance catheter evaluation was not. Following
      pericardiotomy, CO decreased by 7.51% (P<0.05). SMR with patent LAD showed
      inotropic properties with improvements in CO, SV, Pmax in-LV and LVEF (P<0.0001).
      Following LAD occlusion, SMR supplied myocardial oxygenation with hemodynamic
      compensation and preserved the peripheral perfusion. Histology confirmed no signs
      of infarct. CONCLUSIONS: SMR showed capacities to produce inotropic effects and
      protect against ischemia, opening interesting perspectives.

PMID- 29327564
TI  - Neo-pulmonary valve fabrication using tissue-engineered pericardium: a new
      surgical technique.

PMID- 29327565
TI  - Durability of fenestrated endovascular aortic repair for juxta-renal abdominal
      aortic aneurysm repair.
AB  - BACKGROUND: The aim of this study was to evaluate the long term durability of
      fenestrated endovascular aortic aneurysm repair (F-EVAR) of juxta-renal aortic
      aneurysms (JAAAs) in terms of mortality, target visceral vessel (TVV) patency and
      Reintervention rates. EVIDENCE ACQUISITION: A systematic review and meta-analysis
      was performed. MEDLINE, CENTRAL, and Cochrane databases were searched with PRISMA
      methodology for studies reporting on F-EVAR of JAAA presenting follow-up >36
      months. Articles with <15 patients, follow-up <36 months, comparison of F-EVAR
      with other treatment modalities were excluded. EVIDENCE SYNTHESIS: Seven non
      randomized retrospective studies of prospectively collected data were analysed
      including 772 patients (mean age and diameter ranging from 71.5 to 74 years and
      from 60 to 65mm, respectively) underwent F-EVAR for JAAA during 2001-2015. The
      pooled mortality rates during 12, 24, 36, 48 and 60 months were 0.080 (0.060
      0.106), 0.129 (0.097-0.169), 0.211 (0.158-0.277), 0.279 (0.193-0.386) and 0.405
      (0.303-0.517), respectively. The pooled Reintervention rates during 12, 24, 36
      and 48 months were 0.097 (0.066-0.140), 0.131 (0.082-0.203), 0.281 (0.182-0.406)
      and 0.244 (0.103-0.477), respectively. The pooled loss of TVV patency rates
      during 12, 24, 36, 48 and 60 months were 0.046 (0.035-0.060), 0.081 (0.058
      0.110), 0.088 (0.060-0.127), 0.123 (0.067-0.214) and 0.132 (0.081-0.207).
      CONCLUSIONS: F-EVAR for the treatment of patients with JAAA is a durable
      procedure with good long term outcomes in terms of mortality and visceral vessels
      patency. During long term period the need for a Reintervention continues to
      exists, thus follow-up of those cases may be important for preserving the good
      results.

PMID- 29327563
TI  - Hemodynamic outcomes of the Ross procedure versus other aortic valve replacement:
      a systematic review and meta-analysis.
AB  - INTRODUCTION: Life expectancy in young adults undergoing mechanical or
      bioprosthetic aortic valve replacement (AVR) may be reduced by up to 20 years
      compared to age matched controls. The Ross procedure is a durable,
      anticoagulation-sparing alternative. We performed a systematic review and meta
      analysis to compare the valve hemodynamics of the Ross procedure versus other
      AVR. EVIDENCE ACQUISITION: We searched Cochrane CENTRAL, MEDLINE and EMBASE from
      inception to February 2017 for randomized controlled trials (RCTs) and
      observational studies (n>=10 Ross). Independently and in duplicate, we performed
      title and abstract screening, full-text eligibility assessment, and data
      collection. We evaluated the risk of bias with the Cochrane and CLARITY tools,
      and the quality of evidence with the GRADE framework. EVIDENCE SYNTHESIS: We
      identified 2 RCTs and 13 observational studies that met eligibility criteria
      (N.=1412). In observational studies, the Ross procedure was associated with a
      lower mean aortic gradient at discharge (MD -9 mmHg, 95% CI: -13 to -5, P<0.0001,
      I2=97%) and latest follow-up (MD -5 mmHg, 95% CI: -7 to -3, P<0.0001, I2=92%).
      There was no significant difference in the incidence of severe aortic
      regurgitation at latest follow-up (RR 1.3, 95% CI: 0.3 to 5.8, P=0.70, I2=30%).
      In RCTs, the Ross procedure was associated with a lower mean gradient at latest
      follow-up (MD -15 mmHg, 95% CI: -32 to 2, P=0.08, I2=99%). The mean pulmonic
      gradient for the Ross procedure was 18.0 mmHg (95% CI: 16 to 20, P<0.0001) at
      latest follow-up. The evidence for all outcomes from observational studies was
      deemed to be of very low quality, while the evidence from RCTs was downgraded for
      imprecision and moderately serious risk of bias. CONCLUSIONS: Compared to
      conventional AVR, the Ross procedure was associated with better aortic valve
      hemodynamics. Future studies should evaluate the impact of the Ross procedure on
      exercise capacity and quality of life.

PMID- 29327566
TI  - Upper extremity access options for complex endovascular aortic interventions.
AB  - The advancement of endovascular therapy has led to minimally invasive solutions
      to increasingly complex aortic pathology, including thoracoabdominal aneurysms
      and those involving the visceral segment. Upper extremity access is beneficial in
      a variety of these complex interventions, and may be absolutely required for
      certain procedures such as placement of parallel chimney grafts. Traditionally,
      the brachial artery has been the primary access site on the arm, using either a
      percutaneous or open approach. Brachial access is safe and effective, and remains
      suitable for the majority of clinical situations. More recently though,
      descriptions of axillary and radial access have emerged and may provide a useful
      alternative in specific cases. These options should be viewed as complementary
      rather than competitive, and facility with all three techniques is desirable.
      Here, we describe in detail the various options for upper extremity access during
      complex aortic aneurysm repair and their relative advantages.

PMID- 29327567
TI  - Does surgical ventricular restoration still represent a valuable option in the
      surgeon's armamentarium in the post-STICH era?

PMID- 29327568
TI  - Is there an age limit for abdominal aortic aneurysm repair?
AB  - INTRODUCTION: There is an increasing number of elderly in society and some of
      them may have an abdominal aortic aneurysm (AAA). The prevalence of AAA in octo-
      and nonagenarians indicates that this number could be substantial. The question
      is: is there an age limit for repair? This complex question incorporates ethical,
      political, economic and medical aspects. To answer part of this question a review
      of the outcome of elective and emergent AAA repair in those over 80 was done.
      EVIDENCE ACQUISITION: A literature research was done in the PubMed and Embase
      databases between 2007 and 2017 for either emergent and/or elective repair of AAA
      in individuals older than 80 years of age. EVIDENCE SYNTHESIS: Ten of 663 studies
      were found eligible for the review. Elective AAA repair in individuals more than
      80 years shows a very varying outcome with 30-day mortality between 0% and 20.1%
      and 1-year mortality between 7% and 26%. Length of procedure, hospital stay, and
      number of major adverse events are also more in those over 80 years of age. In
      ruptured AAA 30-day mortality is between 29 and 59 % and 1 one year between 45%
      and 63%. CONCLUSIONS: No definitive answer whether to perform a repair of AAA in
      the elderly can be given. The decision has to be individualized and will also
      vary depending on ethical, political, economic factors and type of healthcare
      system the individual lives in.

PMID- 29327569
TI  - Combination of endovascular revascularization and supervised exercise therapy for
      intermittent claudication: a systematic review and meta-analysis.
AB  - BACKGROUND: Peripheral arterial disease is a major health concern in the Western
      world, often treated with endovascular revascularization (EVR) or supervised
      exercise therapy (SET). In this systematic review and meta-analysis, we assessed
      the outcomes after combination treatment of EVR and SET, compared with EVR or SET
      alone. EVIDENCE ACQUISITION: We performed a systematic search of Embase, Medline,
      Web of Science, Cochrane Central and Google Scholar. Only randomized controlled
      trials comparing combination treatment with EVR or SET only, for patients with
      intermittent claudication due to femoropopliteal or aortoiliac peripheral artery
      disease, were included. Primary outcome was maximum walking distance (MWD) at 6
      and 12 months' follow-up. Secondary outcomes included pain-free walking distance
      (PFWD), quality of life and adverse events. Pooled estimates of difference in
      walking distance between EVR plus SET, EVR only and SET only were calculated
      using random effects models. EVIDENCE SYNTHESIS: Our search yielded 812 articles,
      of which 7 were finally included in the systematic review. Three studies reported
      the outcomes of combination treatment versus SET and three more reported the
      outcomes of combination versus EVR. Follow-up ranged between 6 and 24 months.
      Combination treatment was associated with a greater MWD at 6 months compared to
      EVR only or SET only, with a standardized mean difference (SMD) of 0.86 (95% CI:
      0.15, 1.57) and 0.41 (95% CI: 0.17, 0.66), respectively. At twelve months no
      significant difference in maximum walking distance was observed between
      combination treatment compared to EVR (SMD 0.96 [95% CI: -0.44, 2.37]) or SET
      (SMD 0.52 [95% CI: -0.17, 1.20]). Compared to EVR only, the combination treatment
      was associated with a greater PFWD walking distance at 12 months (SMD 0.73 [95%
      CI 0.01, 1.45]). Most studies reported only minor differences in quality of life
      in favor of the combination treatment, or no difference at all. CONCLUSIONS:
      Combination treatment of endovascular revascularization followed by SET shows a
      greater improvement in maximum walking distance at 6 months' follow-up compared
      to EVR only or SET only, while this difference was no longer present after 12
      months.

PMID- 29327570
TI  - The DETOUR procedure: no more need for conventional bypass surgery?
AB  - BACKGROUND: Long segment occlusive disease in the superficial femoral artery
      remains a treatment challenge despite advances in open surgical and endovascular
      approaches. We report initial clinical results of an entirely new procedure to
      perform percutaneous femoro-popliteal bypass using the DETOUR System. First-in
      human patients were performed in New Zealand from December 2013 to June 2014.
      After modifications to the technique and devices had significantly refined the
      procedure, the Detour I Trial commenced. METHODS: Review of initial results in
      the first five patients treated at a single site enrolled in IRB-approved,
      prospective clinical study using the DETOUR System. All patients signed informed
      consent with planned 2-year follow-up. The DETOUR System was used to create a
      stent graft bypass which originates in the SFA, travels through the femoral vein,
      and ends in the popliteal artery, bypassing the diseased segment. RESULTS: A
      cohort of patients were treated in Latvia from January 2015 to October 2015. The
      initial five patients in this cohort (age 67.2+/-11.4 years) with long femoral
      artery occlusions (29.5+/-14.1 cm) were treated at a single clinical site. TORUS
      stent grafts were successfully implanted in all 5 patients (100%) using an 8F
      delivery system. There were no perioperative 30-day major adverse events (death,
      major bleeding, deep vein thrombosis, target vessel revascularization or major
      amputation) observed. At 24 months' follow-up, the primary patency rate was 80%
      (4/5) and primary assisted patency was 100% (5/5). Significant improvement in
      ankle-brachial index and Rutherford class were observed in all patients. There
      was a single secondary procedure performed in these patients (proximal stent edge
      stenosis at 24 months). The venous function has not been damaged or compromised
      in any patient. CONCLUSIONS: Early results suggest that properly-selected
      patients with long-segment occlusive disease above the knee can be safely treated
      using the DETOUR System for percutaneous bypass, with favorable clinical outcomes
      extending to 2 years. Further clinical investigation is warranted to evaluate the
      role of this approach in the treatment of long femoral lesions.

PMID- 29327571
TI  - The current state of flexide catheter robotics for endovascular interventions.

PMID- 29327572
TI  - Endovascular treatment of isolated abdominal aortic dissection.

PMID- 29327573
TI  - Treating complex femoropopliteal lesions.
AB  - Peripheral artery disease affects 202 million patients worldwide and may cause
      disabling intermittent claudication and critical limb ischemia. Next to life
      style changes, best medical treatment and supervised exercise therapy, it can be
      necessary to re-vascularize the limb. Treatment of femoropopliteal lesions poses
      a challenge and a surgical bypass remains recommended in the guidelines for
      longer and more complex lesions. Bypass surgery is associated with substantial
      morbidity and even mortality. Endovascular alternatives are quickly evolving from
      plain balloon angioplasty to drug-eluting stents, drug-coated balloons,
      polytetrafluoroethylene-covered stents and atherectomy. These developments might
      challenge the gold standard in the near future. This article focuses on which
      technique can be used for which femoropopliteal lesion, particularly complex
      lesions, and summarizes the most recent and important literature on this topic.

PMID- 29327574
TI  - Review on management and outcomes of ruptured abdominal aortic aneurysm in women.
AB  - Vascular procedures in general, and specifically abdominal aortic aneurysm (AAA)
      repair, are associated with worse outcomes in female patients. However, how
      female gender influences outcomes in the setting of aneurysm-rupture remains
      unclear and may be even more pronounced when compared to elective operations. In
      this report, the authors aim to review the literature regarding ruptured AAA
      repair in women. Using the traditional threshold for AAA of 30 mm of maximum
      diameter, the prevalence in women is lesser than in men. However, the true
      prevalence may be underestimated due to gender discrepancies in normal aortic
      diameter. For females, aneurysmal disease seems to manifest later, have more
      associated comorbidities, and rupture occurs at smaller aortic diameters. This
      has obvious implications for management. There is still no consensus over the
      optimal treatment for ruptured AAA in women. They are less frequently treated by
      endovascular aneurysm repair, possibly due to anatomical restrains. When
      feasible, endovascular repair shows better outcomes, at least in the short-term,
      and there is new evidence suggesting a lasting benefit as well. For open repair
      the results are consensually worse when compared to male counterparts. Finally,
      despite benefitting of apparently similar healthcare, women have a lower relative
      survival after rAAA repair when compared to men. Further investigation to
      determine the reasons of these discrepancies is warranted.

PMID- 29327575
TI  - The revolution of transcatheter aortic valve implantation.

PMID- 29327576
TI  - Is EVAR a durable solution? Indications for reinterventions.
AB  - INTRODUCION: Indications for reinterventions after endovascular aneurysm repair
      (EVAR), as well as their occurrence in number and time, are important to
      establish in order to optimize patient selection, postprocedure surveillance and
      also to guide improvements in endograft designs. The aim of this report was to
      present an overview of current data on reinterventions after elective EVAR.
      EVIDENCE ACQUISITION: Qualitative review of studies reporting on reinterventions
      after elective EVAR, identified by a systematic literature search in MEDLINE,
      EMBASE and the Cochrane Library for publications from 2010 to 13th of November
      2017. EVIDENCE SYNTHESIS: Twenty-three studies reporting on 83,307 patients met
      the inclusion criteria. Index procedures were performed between 1996-2014. There
      was wide heterogeneity in reporting standards. Type I endoleaks were reported in
      0.6%-13% and type III endoleaks in 0.9-2.1% with a significant improvement for
      newer devices. Migration rates varied between 0-4%. Endoleak type II was the most
      common indication for re-intervention ranging from 14-25.3% although the majority
      resolved without intervention. Rupture rates ranged from 0-5.4% and carried a
      high mortality (60-67%). Ruptures occurred at any time after the index procedure.
      Limb ischemia rates were reported at 0.4-11.9% with re-intervention rates between
      0.06-11.9%. Wound related complications and related re-interventions were the
      indication in 0.5-14% and 0.3-6.5%, respectively. Endograft infection carried a
      high risk of mortality and was described in 0.3-3.6%, often related to graft
      enteric fistula and the majority had an open explantation of the endograft.
      CONCLUSIONS: This review showed that the rates of complications and techniques
      for reintervention developed over time with a tendency towards better outcomes
      considering the aneurysm related indications. Significant factors that led to
      subsequent secondary interventions were migration, rupture, infections and type I
      and II endoleaks. Patients treated with earlier generation endografts are still
      alive and need continued surveillance to detect these severe complications before
      they lead to rupture.

PMID- 29327577
TI  - Interplay of Interfacial Layers and Blend Composition To Reduce Thermal
      Degradation of Polymer Solar Cells at High Temperature.
AB  - The thermal stability of printed polymer solar cells at elevated temperatures
      needs to be improved to achieve high-throughput fabrication including annealing
      steps as well as long-term stability. During device processing, thermal annealing
      impacts both the organic photoactive layer, and the two interfacial layers make
      detailed studies of degradation mechanism delicate. A recently identified
      thermally stable poly[[4,8-bis[(2-ethylhexyl)oxy]benzo[1,2-b:4,5-b']dithiophene
      2,6-diyl][3-fluoro-2-[(2-ethylhexyl)carbonyl]thieno[3,4-b]thiophenediyl]]:[6,6]
      phenyl-C71-butyric acid methyl ester (PTB7:PC70BM) blend as photoactive layer in
      combination with poly(3,4-ethylenedioxythiophene) polystyrene sulfonate as hole
      extraction layer is used here to focus on the impact of electron extraction layer
      (EEL) on the thermal stability of solar cells. Solar cells processed with densely
      packed ZnO nanoparticle layers still show 92% of the initial efficiency after
      constant annealing during 1 day at 140  degrees C, whereas partially covering ZnO
      layers as well as an evaporated calcium layer leads to performance losses of up
      to 30%. This demonstrates that the nature and morphology of EELs highly influence
      the thermal stability of the device. We extend our study to thermally unstable
      PTB7:[6,6]-phenyl-C61-butyric acid methyl ester (PC60BM) blends to highlight the
      impact of ZnO on the device degradation during annealing. Importantly, only 12%
      loss in photocurrent density is observed after annealing at 140  degrees C during
      1 day when using closely packed ZnO. This is in stark contrast to literature and
      addressed here to the use of a stable double-sided confinement during thermal
      annealing. The underlying mechanism of the inhibition of photocurrent losses is
      revealed by electron microscopy imaging and spatially resolved spectroscopy. We
      found that the double-sided confinement suppresses extensive fullerene diffusion
      during the annealing step, but with still an increase in size and distance of the
      enriched donor and acceptor domains inside the photoactive layer by an average
      factor of 5. The later result in combination with comparably small photocurrent
      density losses indicates the existence of an efficient transport of minority
      charge carriers inside the donor and acceptor enriched phases in PTB7:PC60BM
      blends.

PMID- 29327578
TI  - Rapid Light-Driven Color Transition of Novel Photoresponsive Polydiacetylene
      Molecules.
AB  - We developed new photoresponsive polydiacetylene (PR-PDA) molecules by
      incorporating a photocleavable moiety, 6-nitropiperonyl alcohol (NP) or 4,5
      dimethoxy-2-nitrobenzyl alcohol (DMN), into a self-assembling diacetylene
      molecule. Inducing steric disordering of the assembled PDA molecules by the
      cleavage of the photoresponsive moiety under 365 nm UV irradiation results in
      color transition from blue to red and development of red fluorescence, allowing
      convenient photo patterning. Further writing and erasing of fluorescence patterns
      are demonstrated toward novel secure information communication and
      anticounterfeiting applications.

PMID- 29327579
TI  - Can Multielectron Intercalation Reactions Be the Basis of Next Generation
      Batteries?
AB  - Intercalation compounds form the basis of essentially all lithium rechargeable
      batteries. They exhibit a wide range of electronic and crystallographic
      structures. The former varies from metallic conductors to excellent insulators.
      The latter often have layer structures or have open tunnel structures that can
      act as the hosts for the intercalation of a wide range of metal cation and other
      guest species. They are fascinating materials with almost infinitely variable
      properties, with the crystal structure controlling the identity and the amount of
      the guest species that may be intercalated and subsequently removed. The
      electronic structure controls not only the degree of electron transfer to the
      host, but also defines the degree of the electrostatic interactions a mobile ion
      experiences; thus, a metallic host will provide a minimizing of those
      interactions, whereas in an ionic lattice the interactions will be much greater
      and the mobile ion will experience a much higher activation energy for motion.
      This becomes more important for multivalent cations such as Mg2+. Today's lithium
      batteries are limited in capacity, because less than one lithium ion is
      reversibly intercalated per transition metal redox center. There may be an
      opportunity to increase the storage capacity by utilizing redox centers that can
      undergo multielectron reactions. This might be accomplished by intercalating
      multiple monovalent cations or one multivalent cation. In this Account, we review
      the key theoretical and experimental results on lithium and magnesium reversible
      intercalation into two prototypical materials: titanium disulfide, TiS2, and
      vanadyl phosphate, VOPO4. Both of these materials exist in two or more phases,
      which have different molar volumes and/or dimensionalities and thus are expected
      to show a range of diffusion opportunities for battery active guest ions such as
      lithium, sodium, and magnesium. One major conclusion of this Account is that
      reversibly intercalating two lithium ions into a host lattice while maintaining
      its crystal structure is possible. A second major conclusion is that theoretical
      studies are now sufficiently mature that they can be relied upon to predict the
      key free energy values of simple intercalation reactions, i.e., the energy that
      might be stored. This could help to focus future choices of battery couples. In
      hindsight, theory would have predicted that magnesium-based intercalation cells
      are not a viable electrochemical option, relative to lithium cells, from either
      power or energy density considerations. However, the fundamental study of such
      reactions will lead to a better understanding of intercalation reactions in
      general, and of the critical importance of crystal structure in controlling the
      rates and degree of chemical reactions.

PMID- 29327580
TI  - Measuring RNA-Ligand Interactions with Microscale Thermophoresis.
AB  - In recent years, there has been dramatic growth in the study of RNA. RNA has gone
      from being known as an intermediate in the central dogma of molecular biology to
      a molecule with a large diversity of structure and function that is involved in
      all aspects of biology. As new functions are rapidly discovered, it has become
      clear that there is a need for RNA-targeting small molecule probes to investigate
      RNA biology and clarify the potential for therapeutics based on RNA-small
      molecule interactions. While a host of techniques exist to measure RNA-small
      molecule interactions, many of these have drawbacks that make them intractable
      for routine use and are often not broadly applicable. A newer technology called
      microscale thermophoresis (MST), which measures the directed migration of a
      molecule and/or molecule-ligand complex along a temperature gradient, can be used
      to measure binding affinities using very small amounts of sample. The high
      sensitivity of this technique enables measurement of affinity constants in the
      nanomolar and micromolar range. Here, we demonstrate how MST can be used to study
      a range of biologically relevant RNA interactions, including peptide-RNA
      interactions, RNA-small molecule interactions, and displacement of an RNA-bound
      peptide by a small molecule.

PMID- 29327581
TI  - Direct Measurement of Large Electrocaloric Effect in Ba(ZrxTi1-x)O3 Ceramics.
AB  - Barium zirconate titanate (BZT) (Ba(ZrxTi1-x)O3) ceramics with Zr4+ contents of x
      = 5, 10, 15, 20, 25, and 30 mol % were prepared using a solid-state reaction
      approach. The microstructures, morphologies, and electric properties were
      characterized using X-ray diffraction, scanning electron microscopy, and
      impedance analysis methods, respectively. The dielectric analyses indicate that
      the BZT bulk ceramics show characteristics of phase transition from a normal
      ferroelectric to a relaxor ferroelectric with the increasing Zr4+ ionic content.
      The electrocaloric effect adiabatic temperature change decreases with the
      increasing Zr4+ content. The highest adiabatic temperature change obtained is 2.4
      K for BZT ceramics with a 5 mol % of Zr4+ ionic content.

PMID- 29327582
TI  - Uranium(VI) On-Chip Microliter Concentration Measurements in a Highly Extended UV
      Visible Absorbance Linearity Range.
AB  - The reduction of effluents deriving from analytical control is a serious concern
      in the nuclear industry, for both production and R&D units. In this work we
      report an alternative methodology for the standard UV-vis absorbance analyses for
      actinides concentration monitoring along the plutonium uranium refining
      extraction (PUREX) process. This methodology, based on photonic lab-on-a-chip
      (PhLoC) technology, enables drastic sampling reduction down to a few microliters
      and simultaneously allows to track concentrations over several orders of
      magnitude while maintaining a detection linearity range. A PhLoC microfluidic
      platform was specifically designed to allow online sample injection with zero
      dead volume connectivity and the on-chip spectrophotometric approach, based on a
      multiple optical path configuration, was tested for the determination of
      uranium(VI) concentrations from 0.1 to 200 g L-1, showing that linearity is
      maintained within high levels of confidence. These results provide the proof of
      concept for the transposition of current analytical methods for actinides,
      including plutonium, to microfluidic systems.

PMID- 29327583
TI  - Asymmetric Total Synthesis of (+)-(3E)-Pinnatifidenyne via Abnormally
      Regioselective Pd(0)-Catalyzed Endocyclization.
AB  - The asymmetric total synthesis of the marine natural product (+)-(3E)
      pinnatifidenyne was accomplished. The key features of the synthesis involve the
      construction of an eight-membered cyclic ether by the abnormally regioselective
      Pd(0)-catalyzed cyclization, the installation of a double bond in the oxocene
      skeleton by sequential in situ deconjugative isomerization, and the efficient
      introduction of the crucial chloride mediated by the substrate-controlled
      diastereoselective reduction.

PMID- 29327584
TI  - Gamma-aminobutyric Acid Enriched Rice Bran Diet Attenuates Insulin Resistance and
      Balances Energy Expenditure via Modification of Gut Microbiota and Short-Chain
      Fatty Acids.
AB  - In this study, gamma-aminobutyric acid (GABA) enriched rice bran (ERB) was
      supplemented to obese rats to investigate the attenuation of metabolic syndromes
      induced by high-fat diet. ERB-containing diet stimulated butyrate and propionate
      production by promoting Anaerostipes, Anaerostipes sp., and associated
      synthesizing enzymes. This altered short-chain fatty acid (SCFA) distribution
      further enhanced circulatory levels of leptin and glucagon-like peptide-1,
      controlling food intake by downregulating orexigenic factors. Together with the
      enhanced fatty acid beta-oxidation highlighted by Prkaa2, Ppara, and Scd1
      expression via AMPK signaling pathway and nonalcoholic fatty liver disease
      pathway, energy expenditure was positively modulated. Serum lipid compositions
      showed ERB supplement exhibited a more efficient effect on lowering serum
      sphingolipids, which was closely associated with the status of insulin
      resistance. Consistently, genes of Ppp2r3b and Prkcg, involved in the function of
      ceramides in blocking insulin action, were also downregulated following ERB
      intervention. Enriched GABA and phenolic acids were supposed to be responsible
      for the health-beneficial effects.

PMID- 29327585
TI  - Photoinduced Generation of Acyl Radicals from Simple Aldehydes, Access to 3-Acyl
      4-arylcoumarin Derivatives, and Evaluation of Their Antiandrogenic Activities.
AB  - A novel photocatalysis to construct the 3-acyl-4-arylcoumarin framework from
      simple aldehyde with ynoate is described. The reaction proceeded through an acyl
      radical intermediate generated by hydrogen atom abstraction from aldehyde,
      followed by reaction with ynoate and then cyclization to afford coumarins. This
      valuable radical cyclization reaction gave over 20 coumarin derivatives in
      moderate to good yields with inexpensive 2-tBu-anthraquinone as a catalyst. In
      addition, synthetic coumarins were investigated for 5alpha-dihydrotestosterone
      (DHT)-induced secretion of prostate-specific antigen (PSA) levels and cell
      proliferation of androgen-dependent CWR22Rv1 cells.

PMID- 29327587
TI  - Conformational Impact on Amino Acid-Surface pi-pi Interactions on a (7,7) Single
      Walled Carbon Nanotube: A Molecular Mechanics Approach.
AB  - A study of pi-pi interactions between a (7,7) single-walled carbon nanotube
      (SWNT) and three different aromatic amino acids (AAA), namely l-tyrosine (Tyr), l
      tryptophan (Trp), and l-phenylalanine (Phe) was conducted with a molecular
      mechanics (MM) approach. For each of the amino acids we investigated the behavior
      of six different conformers. We examined the impact of the so-called edge effects
      by testing the parameters of the built-in switching function in MM. We found the
      optimal SWNT length to be approximately 80 A for the size of the molecules in our
      conformational studies. The positional effect of electron withdrawing groups with
      respect to the aromatic tail was studied to understand the influence of this
      interaction specific to adsorption strength and geometry. We decomposed the
      aromatic amino acid-surface interactions into three components: overall energy,
      aromatic ring, and amino acid head adsorption energies. We found that the ability
      of the amino acid's head to interact with the surface pi-densities had a greater
      impact on the overall energy than the amino acid head interaction with its
      substituent's aromatic ring's pi-electrons.

PMID- 29327586
TI  - Composite Hydrogel Modified by IGF-1C Domain Improves Stem Cell Therapy for Limb
      Ischemia.
AB  - Stem cell treatment for critical limb ischemia yields a limited therapeutic
      effect due to cell loss and dysfunction caused by local ischemic environment.
      Biomimetic scaffolds emerge as ideal cell delivery vehicles for regulating cell
      fate via mimicking the components of stem cell niche. Herein, we prepared a
      bioactive hydrogel by mixing chitosan and hyaluronic acid that is immobilized
      with C domain peptide of insulin-like growth factor 1 (IGF-1C) and examined
      whether this hydrogel could augment stem cell survival and therapeutic potential.
      Our results showed that IGF-1C-modified hydrogel increased in vitro viability and
      proangiogenic activity of adipose-derived stromal cells (ADSCs). Moreover,
      cotransplantation of hydrogel and ADSCs into ischemic hind limbs of mice
      effectively ameliorated blood perfusion and muscle regeneration, leading to
      superior limb salvage. These therapeutic effects can be ascribed to improved ADSC
      retention, angiopoientin-1 secretion, and neovascularization, as well as reduced
      inflammatory cell infiltration. Additionally, hydrogel enhanced antifibrotic
      activity of ADSCs, as evidenced by decreased collagen accumulation at late stage.
      Together, our findings indicate that composite hydrogel modified by IGF-1C could
      promote survival and proangiogenic capacity of ADSCs and thereby represents a
      feasible option for cell-based treatment for critical limb ischemia.

PMID- 29327588
TI  - Directing Oxygen Vacancy Channels in SrFeO2.5 Epitaxial Thin Films.
AB  - Transition-metal oxides (TMOs) with brownmillerite (BM) structures possess one
      dimensional oxygen vacancy channels (OVCs), which play a key role in realizing
      high ionic conduction at low temperatures. The controllability of the vacancy
      channel orientation, thus, possesses a great potential for practical applications
      and would provide a better visualization of the diffusion pathways of ions in
      TMOs. In this study, the orientations of the OVCs in BM-SrFeO2.5 are stabilized
      along two crystallographic directions of the epitaxial thin films. The
      distinctively orientated phases are found to be highly stable and exhibit a
      considerable difference in their electronic structures and optical properties,
      which could be understood in terms of orbital anisotropy. The control of the OVC
      orientation further leads to modifications in the hydrogenation of the BM
      SrFeO2.5 thin films. The results demonstrate a strong correlation between
      crystallographic orientations, electronic structures, and ionic motion in the BM
      structure.

PMID- 29327589
TI  - Transition Metal Dichalcogenide Nanosheets for Visual Monitoring PCR Rivaling a
      Real-Time PCR Instrument.
AB  - Monitoring the progress of polymerase chain reactions (PCRs) is of critical
      importance in bioanalytical chemistry and molecular biology. Although real-time
      PCR thermocyclers are ideal for this purpose, their high cost has limited their
      applications in resource-poor areas. Direct visual detection would be a more
      attractive alternative. To monitor the PCR amplification, DNA-staining dyes, such
      as SYBR Green I (SG), are often used. Although these dyes give higher
      fluorescence when binding to double-stranded DNA products, they also yield strong
      background fluorescence in the presence of a high concentration of single
      stranded (ss) DNA primers. In this work, we screened various nanomaterials and
      found that graphene oxide (GO), reduced GO, molybdenum disulfide (MoS2), and
      tungsten disulfide (WS2) can quench the fluorescence of nonamplified negative
      samples while still retaining strong fluorescence of positive ones. The signal
      ratio of positive-over-negative samples was enhanced by around 50-fold in the
      presence of these materials. In particular, MoS2 and WS2 nearly fully retained
      the fluorescence of the positive samples. The mechanism for MoS2 and WS2 to
      enhance PCR signaling is attributed to the adsorption of both the ssDNA PCR
      primers and SG with an appropriate strength. MoS2 can also suppress nonspecific
      amplification caused by excess polymerase. Finally, this method was used to
      detect extracted transgenic soya GTS 40-3-2 DNA after PCR amplification. Compared
      with the samples without nanomaterials, the addition of MoS2 could better
      distinguish the concentration difference of the template DNA, and the sensitivity
      of visual detection rivaled that from a real-time PCR instrument.

PMID- 29327590
TI  - Simple Strategy for Rapid and Sensitive Detection of Avian Influenza A H7N9 Virus
      Based on Intensity-Modulated SPR Biosensor and New Generated Antibody.
AB  - In 2013 a new reassortant avian influenza A H7N9 virus emerged in China, causing
      human infection with high mortality. An accurate and timely diagnosis is crucial
      for controlling the outbreaks of the disease. We therefore propose a simple
      strategy for rapidly and sensitively detecting the H7N9 virus using an intensity
      modulated surface plasmon resonance (IM-SPR) biosensor integrated with a new
      generated monoclonal antibody. The novel antibody exhibits significant
      specificity to recognize H7N9 virus compared with other clinical human influenza
      isolates (p < 0.01). Experimentally, the detection limit of the proposed approach
      for H7N9 virus detection is estimated to be 144 copies/mL, which is a 20-fold
      increase in sensitivity compared with homemade target-captured ELISA using the
      identical antibody. For the measurement of mimic clinical specimens containing
      the H7N9 virus mixed with nasal mucosa from flu-like syndrome patients, the
      detection limit is calculated to be 402 copies/mL, which is better than
      conventional influenza detection assays; quantitative reverse transcription
      polymerase chain reaction (qRT-PCR) and rapid influenza diagnostic test (RIDT).
      Most importantly, the assay time took less than 10 min. Combined, the results of
      this study indicate that the proposed simple strategy demonstrates high
      sensitivity and time-saving in H7N9 virus detection. By incorporating a high
      specific recognizer, the proposed technique has the potential to be used in
      applications and development of other emerging or re-emerging microbe detection
      platforms.

PMID- 29327591
TI  - Post-Ugi Cascade Transformations for Accessing Diverse Chromenopyrrole
      Collections.
AB  - Employing a build/couple/pair strategy, a serendipitous one-pot protocol for the
      diastereoselective construction of diverse collections of chromenopyrroles is
      described. This methodology features an unprecedented five-step cascade including
      azomethine ylide generation followed by in situ intramolecular [3 + 2]
      cycloaddition. Furthermore, this protocol was extended to access enantiopure
      chromenopyrroles using amino acids as chiral auxiliary. Moreover, postpairing
      reactions were employed to increase the diversity and complexity of our pilot
      compound collections.

PMID- 29327592
TI  - Sulfonium Salts as Alkylating Agents for Palladium-Catalyzed Direct Ortho
      Alkylation of Anilides and Aromatic Ureas.
AB  - A novel method for the ortho alkylation of acetanilide and aromatic urea
      derivatives via C-H activation was developed. Alkyl dibenzothiophenium salts are
      considered to be new reagents for the palladium-catalyzed C-H activation
      reaction, which enables the transfer of methyl and other alkyl groups from the
      sulfonium salt to the aniline derivatives under mild catalytic conditions.

PMID- 29327593
TI  - The impact of age and gender on the ICF-based assessment of chronic low back
      pain.
AB  - PURPOSE: To evaluate the impact of age and gender on the international
      classification of functioning, disability and health (ICF)-based assessment for
      chronic low back pain. METHODS: Two hundred forty-four chronic low back pain
      patients (52% female) with a mean age of 49 years (SD =17.64) were interviewed
      with the comprehensive ICF core set for activities and participation, and
      environmental factors. After conducting explorative factor analysis, the impact
      of age and gender on the different factors was analyzed using analyzes of
      variances. RESULTS: Results revealed that older patients experienced more
      limitations within "self-care and mobility" and "walking" but less problems with
      "transportation" compared to younger patients. Older or middle-aged low back pain
      patients further perceived more facilitation through "architecture and products
      for communication", "health services", and "social services and products for
      mobility" than younger patients. Regarding gender differences, women reported
      more restriction in "housework" than men. An interaction effect between age and
      gender was found for "social activities and recreation" with young male patients
      reporting the highest impairment. CONCLUSIONS: The study demonstrated that the
      comprehensive ICF core set classification for chronic low back pain is influenced
      by age and gender. This impact is relevant for ICF-based assessments in clinical
      practice, and should be considered in intervention planning for rehabilitative
      programs. Implications for rehabilitation It is important to consider age and
      gender differences when classifying with the ICF. The intervention planning based
      on the ICF should focus on improvement of bodily functioning and mobility in
      older patients, facilitation of household activities in women, consideration of
      work-life balance and recreation (e.g., through mindfulness based stress
      reduction), and reduction of dissatisfaction with rehabilitation in younger
      patients. It is important to offer patients the opportunity to participate in
      intervention planning based on the ICF. For intervention planning professionals
      should bear in mind the resource-oriented approach of the ICF (e.g., facilitation
      through environmental factors), and a collaboration with other professionals.

PMID- 29327595
TI  - The pretransplant neutrophil-lymphocyte ratio as a new prognostic predictor after
      liver transplantation for hepatocellular cancer: a systematic review and meta
      analysis.
AB  - AIM: Recently, many reports showed that the pretransplant neutrophil-lymphocyte
      ratio (NLR) may be correlated with the prognosis of patients undergoing liver
      transplantation (LT) for hepatocellular cancer (HCC). However, their results
      still remained controversial. Thus we performed a meta-analysis of 13 studies to
      estimate the prognostic value of pretransplant NLR. METHODS: Databases including
      PubMed, Embase, Cochrane Library and Web of Science were searched to September
      2017. Hazard ratio (HR) or odds ratio (OR) with its 95% CI was used to evaluate
      the association between elevated NLR and the prognosis or clinical features of
      liver cancer patients. RESULTS: A total of 13 studies including 1936 patients
      were included in this meta-analysis. Elevated pretransplant NLR had a close
      association with the overall survival (HR: 2.22; 95% CI: 1.34-3.68), recurrence
      free survival (HR: 3.77; 95% CI: 2.01-7.06) and disease-free survival (HR: 2.51;
      95% CI: 1.22-5.15) of patients undergoing LT for HCC, respectively. In addition,
      elevated NLR was associated with the presence of vascular invasion (OR: 2.39; 95%
      CI: 1.20-4.77) and Milan criteria (OR: 0.26; 95% CI: 0.17-0.40). CONCLUSION: The
      results of this meta-analysis showed that elevated pretransplant NLR may be used
      as a new prognostic predictor after LT for HCC.

PMID- 29327596
TI  - Fertility preservation in BRCA-mutated women: when and how?
AB  - BRCA 1 and 2 genes play a critical role in the safeguarding of DNA integrity. It
      is now well established that BRCA1 and BRCA2-mutated women are at increased risk
      of breast and ovarian cancers. However, several lines of evidence indicate that
      this genetic status may also be associated with ovarian dysfunction, in
      particular a reduced ovarian reserve. Considering the gonadal toxicity of cancer
      treatments and the recommendation of prophylactic bilateral salpingo-oophorectomy
      around 40 years, young BRCA mutation carriers are confronted with difficult
      family planning decisions. Recent development in fertility preservation offers
      new possibilities for these women, not only before a potential cancer treatment,
      but also in healthy carriers. If the pregnancy seems to be safe in this
      population, oocyte vitrification following ovarian stimulation might help BRCA
      mutated patients to conceive after cancer treatment or to undergo prenatal
      genetic diagnosis in order to avoid the risk of transmitting the genetic
      abnormality to their offspring. The present article aims to extensively discuss
      the fertility issues related to BRCA gene mutations and the questions raised by
      the possibility of fertility in this population.

PMID- 29327597
TI  - Endothelial cell-derived microvesicles: potential mediators and biomarkers of
      pathologic processes.
AB  - This review focuses on the formation, composition and function of endothelial
      microvesicles (MV), often called microparticles (MP). MV release is a controlled
      event and is considered a hallmark of cellular activation or alteration. MV may
      affect the function of target cells through surface interaction and receptor
      activation, cellular fusion and the delivery of intravesicular cargo. Endothelial
      MV are released as a consequence of endothelial activation during inflammation
      and have been described to affect hemostasis, various aspects of inflammatory
      reaction, vessel formation, apoptosis and cell survival, endothelial cell
      differentiation and function. Recent data suggest the potential use of MV in
      diagnostics, assessment of severity and prediction of outcomes in inflammatory
      diseases and their utilization as targets, mediators and vectors in therapy.

PMID- 29327594
TI  - Liver Resection and Surgical Strategies for Management of Primary Liver Cancer.
AB  - Primary liver cancer-including hepatocellular carcinoma (HCC) and intrahepatic
      cholangiocarcinoma (ICC)-incidence is increasing and is an important source of
      cancer-related mortality worldwide. Management of these cancers, even when
      localized, is challenging due to the association with underlying liver disease
      and the complex anatomy of the liver. Although for ICC, surgical resection
      provides the only potential cure, for HCC, the risks and benefits of the multiple
      curative intent options must be considered to individualize treatment based upon
      tumor factors, baseline liver function, and the functional status of the patient.
      The principles of surgical resection for both HCC and ICC include margin-negative
      resections with preservation of adequate function of the residual liver. As the
      safety of surgical resection has improved in recent years, the role of liver
      resection for HCC has expanded to include selected patients with preserved liver
      function and small tumors (ablation as an alternative), tumors within Milan
      criteria (transplant as an alternative), and patients with large (>5 cm) and
      giant (>10 cm) HCC or with poor prognostic features (for whom surgery is
      infrequently offered) due to a survival benefit with resection for selected
      patients. An important surgical consideration specifically for ICC includes the
      high risk of nodal metastasis, for which portal lymphadenectomy is recommended at
      the time of hepatectomy for staging. For both diseases, onco-surgical strategies
      including portal vein embolization and parenchymal-sparing resections have
      increased the number of patients eligible for curative liver resection by
      improving patient outcomes. Multidisciplinary evaluation is critical in the
      management of patients with primary liver cancer to provide and coordinate the
      best treatments possible for these patients.

PMID- 29327598
TI  - Sensitivity to change of mobility measures in musculoskeletal conditions on lower
      extremities in outpatient rehabilitation settings.
AB  - STUDY DESIGN: Prospective longitudinal study. OBJECTIVE: To examine the
      sensitivity of the Mobility Activities Measure for lower extremities and to
      compare it to the sensitivity of the Physical Functioning Scale (PF-10) and the
      Patient-Specific Functional Scale (PSFS) at week 4 and week 8 post
      hospitalization in outpatient rehabilitation settings. BACKGROUND: Mobility
      Activities Measure is a set of short mobility measures to track outpatient
      rehabilitation progress: its scales have shown good properties but its
      sensitivity to change has not been reported. METHODS: Patients with
      musculoskeletal conditions were recruited at admission in three outpatient
      rehabilitation settings in Spain. Data were collected at admission, week 4 and
      week 8 from an initial sample of 236 patients (mean age +/- SD = 36.7 +/- 11.1).
      MAIN OUTCOME MEASURES: Mobility Activities Measure scales for lower extremity; PF
      10; and PSFS. RESULTS: All the Mobility Activities Measure scales were sensitive
      to both positive and negative changes (the Standardized Response Means (SRMs)
      ranged between 1.05 and 1.53 at week 4, and between 0.63 and 1.47 at week 8). The
      summary measure encompassing the three Mobility Activities Measure scales
      detected a higher proportion of participants who had improved beyond the minimal
      detectable change (MDC) than detected by the PSFS and the PF-10 both at week 4
      (86.64% vs. 69.81% and 42.23%, respectively) and week 8 (71.14% vs. 55.65% and
      60.81%, respectively). CONCLUSIONS: The three Mobility Activities Measure scales
      assessing the lower extremity can be used across outpatient rehabilitation
      settings to provide consistent and sensitive measures of changes in patients'
      mobility. Implications for rehabilitation All the scales of the Mobility
      Activities Measure for the lower extremity were sensitive to both positive and
      negative change across the follow-up periods. Overall, the summary measure
      encompassing the three Mobility Activities Measure scales for the lower extremity
      appeared more sensitive to positive changes than the Physical Functioning Scale,
      especially during the first four weeks of treatment. The summary measure also
      detected a higher percentage of participants with positive change that exceeded
      the minimal detectable change than the Patient-Specific Functional Scale and the
      Physical Functioning Scale at the first follow-up period. By demonstrating their
      consistency and sensitivity to change, the three Mobility Activities Measures
      scales can now be considered in order to track patients' functional progress.
      Mobility Activities Measure can be therefore used in patients with
      musculoskeletal conditions across outpatient rehabilitation settings to provide
      estimates of change in mobility activities focusing on the lower extremity.

PMID- 29327599
TI  - Motor skills, cognition, and work performance of people with severe mental
      illness.
AB  - PURPOSE: Employment offers many benefits to people with mental illness, yet their
      employment rate is much lower than that of the general population. We
      investigated the effect of work-related motor skills, neurocognition, and job
      attitudes on the work performance of people with mental illness, comparing those
      working in sheltered workshops, with controls working in similar jobs. METHODS:
      Twenty-nine adults with severe mental illness and 27 controls matched by gender
      and age were enrolled into the study using convenience sampling. They were
      assessed for gross and fine motor hand functioning, job attitudes, work
      performance, and cognition. RESULTS: People with mental illness scored lower on
      work performance, cognitive functioning, and hand dexterity while sitting and
      working with tools. They were assigned lower job loads than were controls, and
      perceived the physical environment at work as more constraining than did
      controls. Assembling motor skills significantly explained the work performance of
      people with mental illness. CONCLUSIONS: The results expand our understanding of
      the complexities involved in the employment of people with severe mental illness,
      and point to new paths for improving vocational outcomes of people with severe
      mental illness, taking into account their motor skills and job attitudes.
      Implications for rehabilitation Therapists should be aware that employed people
      with severe mental illness may have various unmet needs, affecting their work
      performance and experience of stress. This study results demonstrate importance
      of motor skills and perception of the work environment for the promotion of
      vocational outcomes among individuals with severe mental illness. Employment of
      people with severe mental illness should be viewed from holistic perspective as
      with general population, rather than focused on traditionally illness-related
      factors.

PMID- 29327600
TI  - Population-based serum omentin-1 levels: paradoxical association with
      cardiometabolic disorders primarily in men.
AB  - AIM: The conflicting relationships of serum omentin with inflammation markers and
      cardiometabolic disorders were investigated. Results & methods: Unselected 864
      population-based middle-aged adults were cross-sectionally studied by sex
      specific omentin tertiles. Men in the lowest omentin tertile (T1) had lower
      systolic blood pressure, HbA1c and glucose values and tended in T3 to higher
      lipoprotein(a) levels. Logistic regression analysis, adjusted for four
      covariates, revealed significant independent associations with the presence of
      hypertension and diabetes only in men. Sex- and age-adjusted odds ratio in gender
      combined for T2 & T3 versus T1 was 1.34 (95% CI: 1.00-1.79) for metabolic
      syndrome. DISCUSSION & CONCLUSION: The elicited adverse relationships of omentin
      1 support the notion of oxidative stress-induced proinflammatory conversion of
      omentin, rendering loss of anti-inflammatory properties.

PMID- 29327601
TI  - Syndecan-1 as a biomarker for sepsis survival after major abdominal surgery.
AB  - AIM: Sepsis is a serious complication following surgery and identification of
      patients at risk is of high importance. Syndecan-1 (sSDC1) levels are known to be
      elevated during sepsis. MATERIALS & METHODS: Fifty-five patients scheduled for
      major abdominal surgery were prospectively included and sSDC1 concentrations were
      measured during hospital stay. RESULTS: Patients with postoperative sepsis showed
      a continued increase of sSDC1 levels and exhibited higher median sSDC1
      concentrations at day 1 compared with nonseptic patients 90.3 versus 16.5 ng/ml.
      A significant association of sSDC1 levels with the incidence of sepsis and death
      was demonstrated. CONCLUSION: This study identifies sSDC1 as potential biomarker
      for sepsis and survival after abdominal surgery.

PMID- 29327602
TI  - Combination Therapy Versus Exercise and Orthotic Support in the Management of
      Pain in Plantar Fasciitis: A Randomized Controlled Trial.
AB  - BACKGROUND: This study aimed at estimating the effectiveness of two commonly used
      modalities-extracorporeal shock wave therapy (ESWT) and low-level laser therapy
      (LLLT)-each combined with usual care (exercises and orthotic supports) in
      comparison to only usual care to relieve pain in patients with plantar fasciitis
      (PF). METHODS: Participants with PF were randomly allocated into 3 groups: ESWT
      (n = 25), LLLT (n = 24), and control (n = 17). All participants received a home
      exercise program with orthotic support. The ESWT group received 2000 shock waves
      with 0.02 mJ/mm2 for 3 sessions, once a week; LLLT group received gallium
      aluminum-arsenide laser with 850 nm wavelength for 10 sessions, 3 times a week.
      Pain was measured by Foot Function Index-pain subscale (FFI-p) and Numerical
      Rating Scale for pain (NRS-p). The scores were recorded at baseline, third week,
      and third month after the treatment. Analysis was performed using repeated
      measures ANOVA. RESULTS: There was a significant improvement in pain over the 3
      months in all groups on both FFI-p ( P < .001) and NRS-p ( P < .001). In NRS-p,
      LLLT group had significantly lower pain than ESWT ( P = .002) at the third week
      and control ( P = .043) and ESWT ( P = .003) at third month. In FFI-p total
      score, ESWT group had higher pain than LLLT ( P = .003) and control ( P = .035)
      groups at third week and LLLT ( P = .010) group at third month. CONCLUSION: When
      LLLT and ESWT were combined with usual care, LLLT was found to be more effective
      than ESWT in reducing pain in PF at short-term follow-up. LEVEL OF EVIDENCE:
      Level II, comparative study.

PMID- 29327603
TI  - A qualitative investigation into the patient-centered goal-setting practices of
      allied health clinicians working in rehabilitation.
AB  - OBJECTIVE: To explore the ways clinicians engage rehabilitation patients in
      patient-centered goal setting and identify factors influencing the goal-setting
      process. DESIGN: Ethnographic study utilizing observed practice-thematic
      analysis. SETTING: Four rehabilitation wards of a large metropolitan hospital in
      Melbourne, Australia. SUBJECTS: Participants included 17 rehabilitation patients,
      18 allied health clinicians and one family member. Disciplines represented were
      speech pathology, occupational therapy, social work and physiotherapy. METHOD:
      Multiple qualitative methods were used. A total of 18 routine goal-setting
      interviews between clinicians and patients were audio recorded and transcribed.
      Together with associated entries in the patient medical record, transcripts were
      coded and developed into themes using thematic analysis. Finally, focus groups
      with clinicians were conducted to validate themes identified. RESULTS: Three
      themes were identified describing factors which influence patient centeredness:
      "a goal-setting collaboration"-the interpersonal exchange between client and
      clinician; "the environment"-physical, temporal and structural; and "clinician
      self-awareness"-clinicians' insight into the ways they influence goal setting.
      The practice of patient-centered goal setting varied considerably between
      clinicians. Goals developed were strongly influenced by the clinician's views,
      although strategies of respect for the patient and reflective listening skills
      increased patient participation and the patient centeredness of goals developed.
      CONCLUSION: Goals developed with rehabilitation patients are more likely to be
      patient-centered when the interaction encourages the patient to express their
      needs and preferences, and these are heard by the clinician. For this to
      influence treatment, it must occur in an environment structured to support and
      value patient-centered goals.

PMID- 29327604
TI  - Strategies to improve recruitment of people with dementia to research studies.
AB  - : Background Low participation in research is one of the key challenges to
      advancing understanding of dementia, and improving the care and treatment of
      those who live with this condition. Nurses and nurse researchers play a vital
      role in recruiting people with dementia to studies, as several countries
      including the United States and the United Kingdom set national targets and
      develop initiatives to encourage more people with dementia to take part in
      research. Aim To highlight the challenges to recruiting people with dementia to
      studies, and to identify strategies that nurses, and in particular, nurse
      researchers can use for overcoming them. Our focus is primarily on the role of
      nurses in recruiting people with dementia to dementia studies, but much of the
      discussion will apply to other health professionals involved in the recruitment
      of people with dementia to research more generally. Discussion Challenges
      discussed include a lack of awareness about research participation opportunities
      and a suitable study partner. We discuss how the nurses' role is to ensure that
      recruitment practices are personalised and responsive to participants' needs and
      situation, rather than target driven. The notion of responsible research is used
      to anchor the discussion. Conclusion Increasing the participation of people with
      dementia in research is a global priority. Nurses and nurse researchers play an
      important role in ensuring that people who take part in research have an optimal
      research experience. IMPLICATIONS FOR PRACTICE: Recruiting people with dementia
      to research studies is a national priority in many countries. With a greater
      understanding of the challenges involved and strategies that can be used to
      overcome them, nurses can have an effective role in the recruitment process and
      research experience.

PMID- 29327605
TI  - Does change in isolated lumbar extensor muscle function correlate with good
      clinical outcome? A secondary analysis of data on change in isolated lumbar
      extension strength, pain, and disability in chronic low back pain.
AB  - PURPOSE: Secondary analysis of data from studies utilising isolated lumbar
      extension exercise interventions for correlations among changes in isolated
      lumbar extension strength, pain, and disability. MATERIALS AND METHODS: Studies
      reporting isolated lumbar extension strength changes were examined for inclusion
      criteria including: (1) participants with chronic low back pain, (2) intervention
      >= four weeks including isolated lumbar extension exercise, (3) outcome measures
      including isolated lumbar extension strength, pain (Visual Analogue Scale), and
      disability (Oswestry Disability Index). Six studies encompassing 281 participants
      were included. Correlations among change in isolated lumbar extension strength,
      pain, and disability. Participants were grouped as "met" or "not met" based on
      minimal clinically important changes and between groups comparisons conducted.
      RESULTS: Isolated lumbar extension strength and Visual Analogue Scale pooled
      analysis showed significant weak to moderate correlations (r = -0.391 to -0.539,
      all p < 0.001). Isolated lumbar extension strength and Oswestry Disability Index
      pooled analysis showed significant weak correlations (r = -0.349 to -0.470, all p
      < 0.001). For pain and disability, isolated lumbar extension strength changes
      were greater for those "met" compared with those "not met" (p < 0.001-0.008).
      CONCLUSIONS: Improvements in isolated lumbar extension strength may be related to
      positive and meaningful clinical outcomes. As many other performance outcomes and
      clinical outcomes are not related, isolated lumbar extension strength change may
      be a mechanism of action affecting symptom improvement. Implications for
      Rehabilitation Chronic low back pain is often associated with deconditioning of
      the lumbar extensor musculature. Isolated lumbar extension exercise has been
      shown to condition this musculature and also reduce pain and disability. This
      study shows significant correlations between increases in isolated lumbar
      extension strength and reductions in pain and disability. Strengthening of the
      lumbar extensor musculature could be considered an important target for exercise
      interventions.

PMID- 29327606
TI  - The effects of joint mobilization on individuals with patellofemoral pain: a
      systematic review.
AB  - OBJECTIVE: To investigate and synthesize the effects of joint mobilization on
      individuals with patellofemoral pain syndrome. DATA SOURCES: Five electronic
      databases (CINAHL, the Cochrane Central Register of Controlled Trials, PubMed,
      Scopus, and SPORTDiscus) were used. REVIEW METHODS: Each database was searched
      from inception to 1 November 2017. Randomized controlled trials investigating a
      manual therapy intervention, with or without co-interventions, for persons with
      patellofemoral pain were included. Two reviewers independently screened the
      retrieved literature and appraised the quality of the selected studies using the
      PEDro rating scale. A third reviewer was used in cases of discrepancy to create a
      consensus. RESULTS: A total of 361 articles were identified in the search. Twelve
      randomized trials with a total of 499 participants were selected for full review.
      Within-group improvements in pain and function were noted for the manual therapy
      groups. Between-group improvements for short-term outcomes (three months or less)
      were greatest when joint mobilization was directed to the knee complex and used
      as part of a comprehensive approach. CONCLUSION: In the articles reviewed, joint
      mobilization appears to be most effective in improving pain and function when
      coupled with other interventions, although its discrete effect is unclear due to
      the reviewed studies' design and reporting.

PMID- 29327607
TI  - Up-regulation of Cav3.1 expression in SH-SY5Y cells induced by lidocaine
      hydrochloride.
AB  - BACKGROUND: Neurotoxicity induced by the local anaesthetics has aroused concern.
      A previous study has shown that an overload of intracellular calcium was involved
      in the neurotoxic effect. Cav3.1 is one of the low-voltage-activated (LVA)
      calcium channels which play a key point to regulate the intracellular calcium ion
      level. This study aimed to investigate the changes of the Cav3.1 expression in
      the SH-SY5Y cells treated with lidocaine hydrochloride. METHODS: The SH-SY5Y
      cells were treated with different concentrations of lidocaine hydrochloride(1 mM,
      5 mM and 10 mM, namely L1 group, L5 group and L10 group) and different exposure
      times (1 h,12 h and 24 h), respectively. Cell viability, Cav3.1 protein and mRNA
      expression were detected. RESULTS: The results showed that cell viability
      decreased and Cav3.1 mRNA and protein expression increased with the concentration
      (from 1 mM to 10 mM) of the lidocaine hydrochloride and exposure time (from 1 h
      to 24 h) to the SH-SY5Y cell line increased. CONCLUSION: Those data showed that
      lidocaine hydrochloride induced SH-SY5Y cell toxicity and up-regulated Cav3.1mRNA
      and protein expression.

PMID- 29327609
TI  - Cross-bridge mechanism of residual force enhancement after stretching in a
      skeletal muscle.
AB  - A muscle model that uses a modified Langevin equation with actomyosin potentials
      was used to describe the residual force enhancement after active stretching.
      Considering that the new model uses cross-bridge theory to describe the residual
      force enhancement, it is different from other models that use passive stretching
      elements. Residual force enhancement was simulated using a half sarcomere
      comprising 100 myosin molecules. In this paper, impulse is defined as the
      integral of an excess force from the steady isometric force over the time
      interval for which a stretch is applied. The impulse was calculated from the
      force response due to fast and slow muscle stretches to demonstrate the
      viscoelastic property of the cross-bridges. A cross-bridge mechanism was proposed
      as a way to describe the residual force enhancement on the basis of the impulse
      results with reference to the compliance of the actin filament. It was assumed
      that the period of the actin potential increased by 0.5% and the amplitude of the
      potential decreased by 0.5% when the half sarcomere was stretched by 10%. The
      residual force enhancement after 21.0% sarcomere stretching was 6.9% of the
      maximum isometric force of the muscle; this value was due to the increase in the
      number of cross-bridges.

PMID- 29327608
TI  - Pregnancy outcomes of women with spina bifida.
AB  - PURPOSE: To assess the pregnancy outcomes of women with spina bifida. MATERIALS
      AND METHODS: We analyzed a population-based cohort of 397 pregnant women with
      spina bifida and 1,083,211 without spina bifida who delivered infants in
      hospitals in Quebec, Canada, 1989-2013. Outcomes included maternal and infant
      morbidity and mortality at delivery. We used log-binomial regression models to
      estimate prevalence ratios (PR) and 95% confidence intervals (CI) for the
      association of maternal spina bifida with pregnancy outcomes, accounting for
      maternal characteristics. RESULTS: Women with spina bifida had a higher
      prevalence of several adverse outcomes compared with women who had no birth
      defects. Maternal risks were highest for intensive care unit admission during the
      delivery hospitalization (PR 3.41, CI 95% 1.56-7.43) and respiratory morbidity
      (PR 9.46, CI 95% 3.31-26.99). Infant risks were greatest for intracranial
      hemorrhage (PR 6.85, CI 95% 2.23-21.08), birth hypoxia (PR 1.64, CI 95% 1.21
      2.22), and hospital length of stay >=14 days (PR 2.56, CI 95% 1.58-4.15). After
      adjustment for confounders, maternal spina bifida was associated with risk of
      oral clefts and abdominal wall defects in infants. CONCLUSIONS: Women with spina
      bifida have an increased risk of severe maternal and infant complications at
      delivery, compared with no spina bifida. Implications for Rehabilitation A
      growing number of women with spina bifida achieve pregnancy, but pregnancy
      outcomes are poorly understood. In a large pregnancy cohort, women with spina
      bifida had a high risk of severe maternal and infant morbidity at delivery. Women
      with spina bifida may benefit from enhanced periconceptional counseling and
      obstetric monitoring by health professionals. Guidelines should be developed for
      rehabilitation care providers to improve the obstetric management of women with
      spina bifida.

PMID- 29327610
TI  - The 44th Congress of the International Society of Oncology and Biomarkers: Rio de
      Janeiro, Brazil, 7-10 September 2017.
AB  - The 44th Congress of the International Society of Oncology and Biomarkers: Rio de
      Janeiro, Brazil, 7-10 September 2017 The 44th congress followed the previous one
      of  International Society of Oncology and Biomarkers (ISOBM) that took place in
      Chicago (USA) in 2016. The title of the 44th Annual congress was: 'Biomarkers in
      oncology: new horizons and challenges in the diagnosis and treatment of cancer' [
      1 ]. The congress was co-organized by ISOBM, European Group on Tumor Markers
      (EGTM) and Brazilian Society of Clinical Pathology SBPC/ML. The event attracted
      more than 180 participants from all over the world. The program offered many
      topics regarding discovery, validation, evaluation and use of tumor biomarkers.
      The presentations were split into the key note lectures, oral presentations,
      poster presentations and satellite symposiums sponsored by companies. The
      congress offered participants the opportunity to link clinical and research
      oncologists to discuss new tools for diagnosis and monitoring of cancer diseases.
      Prominent people in the field of cancer research and clinical oncology were
      presented and offered the unique opportunity to exchange experiences and
      knowledge in an international forum [ 2 ]. Compared with previous ISOBM
      congresses, it was held in Latin America for the first time, and due to that more
      participants from Latin America were present.

PMID- 29327611
TI  - miRNA-20a upregulates TAK1 and increases proliferation in osteosarcoma cells.
AB  - AIM: The aim of this study is to explore the function of miR-20a in osteosarcoma.
      MATERIALS & METHODS: miR-20a expression was measured by real-time PCR. miR-20a
      mimics, inhibitor and scramble siRNA were transfected into osteosarcoma cells to
      observe effects on colony formation and tumor growth. Moreover, relationships of
      miR-20a with TAK1 were investigated by western blot and luciferase activity.
      RESULTS: We found that miR-20a was downregulated in osteosarcoma, and
      overexpression of miR-20a reduced colony formation and tumor growth. Furthermore,
      the data revealed that the function of miR-20a was probably exerted via targeting
      the TAK1 expression. Overexpression of miR-20a sensitizes the osteosarcoma cells
      to chemotherapeutic drugs. CONCLUSION: Our data identify the role of miR-20a in
      osteosarcoma growth, indicating its potential application in chemotherapy.

PMID- 29327612
TI  - The evidence for expanded genetic testing for pediatric patients with cancer.

PMID- 29327614
TI  - Intracellular African swine fever virus DNA remains unmethylated in infected Vero
      cells.
AB  - AIM: Sequence-specific CpG methylation of eukaryotic promoters is an important
      epigenetic signal for long-term gene silencing. We have now studied the
      methylation status of African swine fever virus (ASFV) DNA at various times after
      infection of Vero cells in culture. METHODS & RESULTS: ASFV DNA was detectable
      throughout the infection cycle and was found unmethylated in productively
      infected Vero cells as documented by bisulfite sequencing of 13 viral DNA
      segments. CONCLUSION: ASFV DNA does not become de novo methylated in the course
      of infection in selected segments spread across the entire genome. Thus DNA
      methylation does not interfere with ASFV genome transcription. Lack of de novo
      methylation has previously been observed for free intracellular viral DNA in
      cells permissively infected with human adenoviruses, with human papillomaviruses
      and others.

PMID- 29327615
TI  - Corrigendum.

PMID- 29327613
TI  - Potential immunotherapies for sarcoidosis.
AB  - INTRODUCTION: Sarcoidosis is a chronic granulomatous inflammatory disease that
      commonly causes lung disease, but can affect other vital organs and tissues. The
      cause of sarcoidosis is unknown, and current therapies are commonly limited by
      lack of efficacy, adverse side effects, and excessive cost. Areas covered: The
      manuscript will provide a review of current concepts relating to the pathogenesis
      of sarcoidosis, and how these disease mechanisms may be leveraged to develop more
      effective treatments for sarcoidosis. It provides only a brief summary of
      currently accepted therapy, while focusing more extensively on potential novel
      therapies. Expert opinion: Current sarcoidosis therapeutic agents primarily
      target the M1 or pro-inflammatory pathways. Agents that prevent M2 polarization,
      a regulatory phenotype favoring fibrosis, are attractive treatment alternatives
      that could potentially prevent fibrosis and associated life threatening
      complications. Effective treatment of sarcoidosis potentially requires
      simultaneous modulation both M1/M2 polarization instead of suppressing one
      pathway over the other to restore immune competent and inactive (M0) macrophages.

PMID- 29327616
TI  - Nintedanib for the treatment of idiopathic pulmonary fibrosis.
AB  - INTRODUCTION: Idiopathic Pulmonary Fibrosis (IPF) is an interstitial lung disease
      characterized by the progressive loss of pulmonary function, ultimately leading
      to respiratory failure and death. Two novel compounds, nintedanib and
      pirfenidone, have shown efficacy in reducing the rate of decline of lung function
      in IPF patients. The multiple tyrosine kinase inhibitor nintedanib has
      extensively being studied as a potential angiogenesis inhibitor in clinical
      against various neoplastic disorders. Afterwards, this compound was successfully
      tested in IPF. Areas covered: Herein, the authors review the working mechanisms
      of nintedanib, its pharmacological profile, and its efficacy and safety for
      patients with IPF. Expert opinion: Nintedanib has shown to be safe and effective
      in patients with IPF, with a favorable long-term safety profile. There is a lack
      of comparative trials of pirfenidone and nintedanib, and the choice of treatment
      is left to the physicians' judgement. Future directions of nintedanib use are
      represented by the treatment of progressive fibrosing interstitial lung disease
      other than IPF, IPF with advanced functional impairment, and lung fibrosis
      secondary to connective tissue diseases. A promising safety profile for the
      combinational use of nintedanib and pirfenidone in IPF has also recently emerged.

PMID- 29327618
TI  - Between Freud's Second and Third Essays on Sexuality: Commentary on Hansbury.

PMID- 29327617
TI  - Presence, Mourning, and Beauty: Elements of Analytic Process.
AB  - Analyst and patient occasionally arrive at moments of heightened meaning and
      aliveness. These moments can be transformative and lead to psychic change in the
      patient. They give life and arouse hope, and feel "real" in a new way, though
      often entailing emotional turbulence. Specific internal work must be done by the
      analyst to allow for and foster these experiences. This involves a kind of
      mourning process in the analyst that allows for "presence" and "availability" as
      described by Gabriel Marcel, and for the "at-one-ment" described by Bion. These
      transforming moments can be viewed in an aesthetic realm, along the lines of
      Keats's "Beauty is truth, truth beauty." This embodies the analytic value of
      emotional truth. These moments are shared and their emergence is an
      intersubjective creation. Clinical illustrations show how the internal work of
      mourning by the analyst through directed introspection allows for presence and
      availability, and then for shared moments of beauty with the patient.

PMID- 29327619
TI  - Body and Symbol: Introduction to Hansbury and Commentators.

PMID- 29327623
TI  - Pussy RIOT: Commentary on Hansbury.

PMID- 29327627
TI  - The Edge is a Horizon: Commentary on Hansbury.

PMID- 29327629
TI  - The Masculine Vaginal: Working With Queer Men's Embodiment at the Transgender
      Edge.
AB  - Turning away from the conspicuous phenomena of transgender experience, with an
      eye toward locating and illuminating the transgender edge in cisgender, this
      paper explores the relationship between men and the Vaginal, both material and
      fantasized. Positing the Vaginal as a counterpart to the Phallic allows a
      delinkage of vaginal psychic and embodied states from the strictly female so
      that, like the Phallic, they can be accessed by people of all genders and sexes.
      This concept goes beyond the conceptual to the fleshy, embodied experience of
      many transgender men, who live in whole, partial, and/or temporary "female"
      bodies. It can also be applied to the physio-psychic reality of many cisgender
      men. Included is a discussion of a case in which a gay cisgender male patient
      experiences and fantasizes his anus as a vagina.

PMID- 29327630
TI  - The Specter of the Primitive.
AB  - Traditional psychoanalytic theories of development hold that the adult neurotic
      can regress, or has already regressed, to the childhood arrests and/or fixations
      in which his pathology originated. More recent critiques have called this
      possibility into question. It is unlikely that anyone can roll back the additions
      and modifications of lifespan development in a full-fledged return to the needs,
      wishes, and anxieties of childhood. By regression, though, some analysts mean not
      a full-fledged return to an earlier developmental phase, but a non-phase-specific
      slip into primitive fantasies and defenses. The operational term, in this
      particular variation, is not regression but primitive. The shift from the
      depressive to the paranoid-schizoid position is, for instance, considered not a
      phase-specific regression but a regression to primitive forms of mentation. The
      psychoanalytic conception of the primitive originated in Freud's reading of late
      nineteenth and early twentieth century anthropology. Freud and later Klein
      believed that the neurotic regresses to a psychological childhood, which in turn
      preserves the thought patterns of our prehistoric ancestors. Although this
      proposition and the underlying principle of recapitulation have been disproven,
      its traces are nonetheless preserved in what are termed the primary processes and
      primitive defenses. A tradition of theoretical critique and developmental
      research, however, shows that the primary processes and primitive defenses are
      not in fact primitive. That is, they are neither evolutionarily nor
      developmentally primary in human life. By implication, psychoanalysis should
      discard the term primitive and adopt a lifespan approach to the processes it
      describes.

PMID- 29327631
TI  - The association between adverse childhood experiences and adult traumatic brain
      injury/concussion: a scoping review.
AB  - BACKGROUND: Adverse childhood experiences are significant risk factors for
      physical and mental illnesses in adulthood. Traumatic brain injury/concussion is
      a challenging condition where pre-injury factors may affect recovery. The
      association between childhood adversity and traumatic brain injury/concussion has
      not been previously reviewed. The research question addressed is: What is known
      from the existing literature about the association between adverse childhood
      experiences and traumatic brain injury/concussion in adults? METHODS: All
      original studies of any type published in English since 2007 on adverse childhood
      experiences and traumatic brain injury/concussion outcomes were included. The
      literature search was conducted in multiple electronic databases. Arksey and
      O'Malley and Levac et al.'s scoping review frameworks were used. Two reviewers
      independently completed screening and data abstraction. RESULTS: The review
      yielded six observational studies. Included studies were limited to incarcerated
      or homeless samples, and individuals at high-risk of or with mental illnesses.
      Across studies, methods for childhood adversity and traumatic brain
      injury/concussion assessment were heterogeneous. DISCUSSION: A positive
      association between adverse childhood experiences and traumatic brain injury
      occurrence was identified. The review highlights the importance of screening and
      treatment of adverse childhood experiences. Future research should extend to the
      general population and implications on injury recovery. Implications for
      rehabilitation Exposure to adverse childhood experiences is associated with
      increased risk of traumatic brain injury. Specific types of adverse childhood
      experiences associated with risk of traumatic brain injury include childhood
      physical abuse, psychological abuse, household member incarceration, and
      household member drug abuse. Clinicians and researchers should inquire about
      adverse childhood experiences in all people with traumatic brain injury as pre
      injury health conditions can affect recovery.

PMID- 29327632
TI  - Defining the target: Competency-based medical education for better patient care.

PMID- 29327634
TI  - Clearing the confusion about self-directed learning and self-regulated learning.
AB  - Self-Directed Learning (SDL) and Self-Regulated Learning (SRL) are often used
      without a clear distinction, leading to confusion in understanding and the use of
      inappropriate measurement tools. SDL is a general approach to learning and can be
      identified using 'aptitude' questionnaires but SRL is a dynamic and context
      specific learning process and requires 'event' measures, such as microanalysis.
      These differences have implications for research and remediation.

PMID- 29327633
TI  - Biochemical basis for the age-related sensitivity of broilers to aflatoxin B1.
AB  - In this study, we investigated the mechanism underlying age-related
      susceptibility in broilers to aflatoxin B1 (AFB1). The results showed that AFB1
      induced significant changes in serum alkaline phosphatase (ALP), alanine
      aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl
      transferase (GGT) activity & liver superoxide dismutase (SOD), malonaldehyde
      (MDA), glutathione peroxidase (GSH-Px) and glutathione S-transferase (GST)
      activity at day 7, 21 and 42 relative to control group. However, AFB1-induced
      changes in serum biochemical parameters and liver antioxidant activities become
      less severe with increasing age of broilers. Particularly, liver cytosolic GST
      activity increases with the age of broilers, crucial for the detoxification of
      AFB1. The mRNA expression level of Cytochrome P450 (CYP) enzymes was
      significantly higher at day 7, and decreases at day 21 and 42. While, the mRNA
      expression level of liver GSTA3, GSTA4 and EPHX1 increases with age of broilers.
      Maximum AFB1 residues level was detected at day 42 relative to day 7 and 21.
      While, AFM1 residues level increases (p < 0.05) from day 7 to 21, but decreases
      (p > 0.05) at day 42. Most importantly, our data confirmed the efficient AFB1
      bioactivation by CYP enzymes and deficient detoxification of GST enzymes at
      younger age (~7-day old) compared to older age. In summary, the age-related
      changes particularly in phase-I and phase-II enzymes mainly responsible for AFB1
      bioactivation and detoxification may be partially accountable for the increased
      susceptibility of younger broilers (~7-day old) compared to older broilers.

PMID- 29327635
TI  - An open label clinical trial of thalidomide in NSAIDs refractory ankylosing
      spondylitis.

PMID- 29327636
TI  - The Norwegian occupational wholeness questionnaire (N-OWQ): Scale development and
      psychometric properties.
AB  - BACKGROUND: Occupational therapy has long emphasized the concepts doing, being,
      becoming and belonging, and a notion of balance between them. Measures of these
      concepts are in a developing stage. AIM: This study aimed to develop and examine
      the properties of the Norwegian version of the Occupational Wholeness
      Questionnaire (N-OWQ), which is proposed to measure being, becoming, and
      belonging, in addition to occupational wholeness as a higher-order concept.
      METHODS: An anonymous sample of 248 persons over the age of 18 years completed
      the N-OWQ along with sociodemographic information. Principal Components Analysis
      (PCA) was performed on the scale items when examining factor structure. Item
      reduction was based on considerations of communalities, factor loadings, scale
      consistency if item deleted, and conceptual issues. Internal consistency was
      assessed with Cronbach's alpha. RESULTS: Following the PCA, the 'Being' and
      'Becoming' scales merged into one five-item 'Self' scale (Cronbach's alpha 0.77).
      The 'Belonging' scale items were split into two scales comprised by three items
      each: 'Closeness' (Cronbach's alpha 0.70) and 'Relatedness' (Cronbach's alpha
      0.73). CONCLUSIONS: The revised N-OWQ merged the 'Being' and 'Becoming' items
      into one factor, whereas the 'Belonging' items were split into two distinct
      factors. Internal consistency for all scales were satisfactory.

PMID- 29327637
TI  - Evidence of shallow mitochondrial divergence in the slender armorhead, Pentaceros
      wheeleri (Pisces, Pentacerotidae) from the Emperor Seamount Chain.
AB  - Competitive overexploitation of the slender armorhead, Pentaceros wheeleri, a
      deep-sea fish inhabiting the Emperor Seamount Chain caused a serious population
      decline. Therefore, it is urgently necessary to clarify its genetic diversity and
      connectivity among populations of P. wheeleri for appropriate stock management.
      For this, we compared 677 base pairs (bp) of mitochondrial (mt) DNA control
      region (CR) sequences of 80 individuals from three seamounts (the Milwaukee,
      Kinmei, and Koko Seamounts) in the southern part of the Emperor Seamount Chain.
      Contrary to our expectation, the three seamount populations showed high genetic
      diversity, not yet reflecting effects from the recent population decline or due
      to mixed two clades. Analysis of molecular variance indicated no significant
      genetic differentiation between seamount populations, however, the neighbour
      joining tree and minimum spanning network showed significant separation into two
      clades (K2P distance= 1.2-3.2%, phist = 0.5739, p < .05) regardless of seamount.
      The divergence time between the two clades was estimated to be 0.3-0.8 Mya,
      during the period of Pleistocene glacial cycles, suggesting that associated
      environmental changes and the unique life history traits of Pentaceros spp. might
      have resulted in the initiation of divergence between these clades.

PMID- 29327638
TI  - Hybrid and surgical procedures for the treatment of persistent and longstanding
      persistent atrial fibrillation.
AB  - INTRODUCTION: Atrial fibrillation (AF) is the most common cardiac arrhythmia. The
      incidence of AF increases with age and is associated with increased stroke, heart
      failure and mortality. Persistent and long standing persistent AF is difficult to
      treat and often refractory to medical therapy and catheter ablation. Areas
      covered: This article reviews the historical development of the surgical Cox-MAZE
      procedure and current hybrid and minimally invasive surgical approaches for the
      treatment of persistent and long standing persistent AF. The role of concomitant
      pulmonary vein isolation and left atrial appendage (LAA) exclusion will also be
      reviewed. Expert commentary: An ablation pattern emulating the Cox-Maze surgical
      procedure is commonly needed to obtain maintenance of sinus rhythm in patients
      with persistent and long standing persistent atrial fibrillation. Minimally
      invasive bilateral thorascopic surgical procedures can achieve a similar Cox-Maze
      lesion set, but are associated with increased adverse events compared to catheter
      ablation. Future prospective randomized studies are required to confirm whether
      the recently developed hybrid subxyphoid epicardial/endocardial procedure and
      percutaneous LAA ligation and catheter ablation are indeed as effective as
      surgical options with less adverse events.

PMID- 29327639
TI  - Levels of uric acid in erectile dysfunction of different aetiology.
AB  - Erectile dysfunction is a common disease characterized by endothelial
      dysfunction. The aetiology of ED is often multifactorial but evidence is being
      accumulated in favor of the proper function of the vascular endothelium that is
      essential to achieving and maintaining penile erection. Uric acid itself causes
      endothelial dysfunction via decreased nitric oxide production. This study aims to
      evaluate the serum uric acid (SUA) levels in 180 ED patients, diagnosed with the
      International Index of Erectile Function-5 (IIEF-5) and 30 non-ED control. Serum
      uric acid was analyzed with a commercially available kit using ModularEVO (Roche,
      Monza, Italy). Within-assay and between-assay variations were 3.0% and 6.0%,
      respectively. Out of the ED patients, 85 were classified as arteriogenic (A-ED)
      and 95 as non-arteriogenic (NA-ED) with penile-echo-color-Doppler. Uric acid
      levels (median and range in mg/dL) in A-ED patients (5.8, 4.3-7.5) were
      significantly higher (p < .001) than in NA-ED patients (4.4, 2.6-5.9) and in
      control group (4.6, 3.1-7.2). There was a significant difference (p < .001)
      between uric acid levels in patients with mild A-ED (IIEF-5 16-20) and
      severe/complete A-ED (IIEF-5 <= 10) that were 5.4 (range 4.3-6.5) mg/dL and 6.8
      (range 6.4-7.2) mg/dL, respectively. There was no difference between the levels
      of uric acid in patients with different degree of NA-ED. Our findings reveal that
      SUA is a marker of ED but only of ED of arteriogenic aetiology.

PMID- 29327640
TI  - Who should be responsible for supporting individuals with mental health problems?
      A critical literature review.
AB  - BACKGROUND: Individuals with mental health problems have many support needs that
      are often inadequately met; however, perceptions of who should be responsible for
      meeting these needs have been largely unexplored. Varying perceptions may
      influence whether, how, and to what extent relevant stakeholders support
      individuals with mental health problems. AIMS: To critically evaluate the
      literature to determine who different stakeholders believe should be responsible
      for supporting individuals with mental health problems, what factors shape these
      perceptions, and how they relate to one another. METHOD: A critical literature
      review was undertaken. Following an extensive literature search, the conceptual
      contributions of relevant works were critically evaluated. A concept map was
      created to build a conceptual framework of the topic. RESULTS: Views of
      individual versus societal responsibility for need provision and health; the
      morality of caring; and attributions of responsibility for mental illness offered
      valuable understandings of the review questions. Creating a concept map revealed
      that various interrelated factors may influence perceptions of responsibility.
      CONCLUSIONS: Varying perceptions of who should be responsible for supporting
      individuals with mental health problems may contribute to unmet support needs
      among this group. Our critical review helps build a much-needed conceptual
      framework of factors influencing perceptions of responsibility. Such a framework
      is essential as these views iteratively shape and reflect the complex divisions
      of mental healthcare roles and responsibilities. Understanding these perceptions
      can help define relevant stakeholders' roles more clearly, which can improve
      mental health services and strengthen stakeholder accountability.

PMID- 29327642
TI  - Effects of Arm Cycling Exercise in Spinal Muscular Atrophy Type II Patients: A
      Pilot Study.
AB  - Exercise studies in neuromuscular diseases like spinal muscular atrophy (SMA), a
      devastating disease caused by survival of motor neuron 1 ( SMN1) gene mutations,
      are drawing attention due to its beneficial effects. In this study, we presented
      a constructed arm cycling exercise protocol and evaluated the benefits on SMA
      patients. Five SMA type II patients performed 12 weeks of supervised arm cycling
      exercise. The physical functions were evaluated together with the SMN2 copy
      numbers, SMN protein levels, insulin-like growth factor 1(IGF1) and binding
      protein 3 (IGFBP3) levels. The active cycling distance and duration of patients
      significantly improved. Significant changes could not have detected either SMN or
      IGF1 and IGFBP3 levels in response to exercise. The findings demonstrated that
      the patients tolerated the exercise protocol and gained a benefit from arm
      cycling but benefits could not be associated with SMN2 copy number, SMN protein
      level, IGF1, or IGFBP3 levels.

PMID- 29327643
TI  - Adherence to biologics in patients with psoriasis.
AB  - INTRODUCTION: Psoriasis has a profound impact on patients' lives, but adherence
      to topical treatment of psoriasis is still poor. Biologic treatment has
      revolutionized the management of psoriasis, but adherence to treatment may still
      be a barrier for some patients. Areas covered: A PubMed search was conducted in
      August 2017 using the terms 'biologics psoriasis adherence' and 'biologics
      psoriasis survival.' Additional articles were obtained by perusing the references
      of articles identified in the original PubMed search. Articles that did not
      specifically mention 'survival,' 'adherence,' or 'persistence' were not included.
      We review the measures used to assess adherence to biologics for psoriasis and
      the factors impacting drug survival and adherence rates for biologics in
      psoriasis. Expert commentary: Drug survival and adherence rates for biologic
      therapy is less than ideal but may be modifiable. Means that may improve
      adherence and drug survival include individualized choice of biologic and
      providing additional support for patients who are at increased risk for
      prematurely stopping treatment.

PMID- 29327641
TI  - Generation of an arrayed CRISPR-Cas9 library targeting epigenetic regulators:
      from high-content screens to in vivo assays.
AB  - The CRISPR-Cas9 system has revolutionized genome engineering, allowing precise
      modification of DNA in various organisms. The most popular method for conducting
      CRISPR-based functional screens involves the use of pooled lentiviral libraries
      in selection screens coupled with next-generation sequencing. Screens employing
      genome-scale pooled small guide RNA (sgRNA) libraries are demanding, particularly
      when complex assays are used. Furthermore, pooled libraries are not suitable for
      microscopy-based high-content screens or for systematic interrogation of protein
      function. To overcome these limitations and exploit CRISPR-based technologies to
      comprehensively investigate epigenetic mechanisms, we have generated a focused
      sgRNA library targeting 450 epigenetic regulators with multiple sgRNAs in human
      cells. The lentiviral library is available both in an arrayed and pooled format
      and allows temporally-controlled induction of gene knock-out. Characterization of
      the library showed high editing activity of most sgRNAs and efficient knock-out
      at the protein level in polyclonal populations. The sgRNA library can be used for
      both selection and high-content screens, as well as for targeted investigation of
      selected proteins without requiring isolation of knock-out clones. Using a
      variety of functional assays we show that the library is suitable for both in
      vitro and in vivo applications, representing a unique resource to study
      epigenetic mechanisms in physiological and pathological conditions.

PMID- 29327644
TI  - Evaluation of supervised multimodal prehabilitation programme in cancer patients
      undergoing colorectal resection: a randomized control trial.
AB  - BACKGROUND: Prehabilitation has been previously shown to be more effective in
      enhancing postoperative functional capacity than rehabilitation alone. The
      purpose of this study was to determine whether a weekly supervised exercise
      session could provide further benefit to our current prehabilition program, when
      comparing to standard post-surgical rehabilitation. METHODS: A parallel-arm
      single-blind randomized control trial was conducted in patients scheduled for non
      metastatic colorectal cancer resection. Patients were assigned to either a once
      weekly supervised prehabilitation (PREHAB+, n = 41) or standard rehabilitation
      (REHAB, n = 39) program. Both multimodal programs were home-based program and
      consisted of moderate intensity aerobic and resistance exercise, nutrition
      counseling with daily whey protein supplementation and anxiety-reduction
      strategies. Perioperative care was standardized for both groups as per enhanced
      recovery after surgery (ERAS(r)) guidelines. Functional exercise capacity, as
      determined by the 6-minute walk test distance (6MWD), was the primary outcome.
      Exercise quantity, intensity and energy expenditure was determined by the CHAMPS
      questionnaire. RESULTS: Both groups were comparable for baseline walking capacity
      (PREHAB+: 448 m [IQR 375-525] vs. REHAB: 461 m [419-556], p=.775) and included a
      similar proportion of patients who improved walking capacity (>20 m) during the
      preoperative period (PREHAB+: 54% vs. REHAB: 38%, p = .222). After surgery,
      changes in 6MWD were also similar in both groups. In PREHAB+, however, there was
      a significant association between physical activity energy expenditure and 6MWD
      (p < .01). Previously inactive patients were more likely to improve functional
      capacity due to PREHAB+ (OR 7.07 [95% CI 1.10-45.51]). CONCLUSIONS: The addition
      of a weekly supervised exercise session to our current prehabilitation program
      did not further enhance postoperative walking capacity when compared to standard
      REHAB care. Sedentary patients, however, seemed more likely to benefit from
      PREHAB+. An association was found between energy spent in physical activity and
      6MWD. This information is important to consider when designing cost-effective
      prehabilitation programs.

PMID- 29327645
TI  - Identification and characterization of chitinolytic bacteria isolated from a
      freshwater lake.
AB  - To develop a novel type of biocontrol agent, we focus on bacteria that are
      characterized by both chitinase activity and biofilm development. Chitinolytic
      bacteria were isolated from sediments and chitin flakes immersed in the water of
      a sand dune lake, Sakata, in Niigata, Japan. Thirty-one isolates from more than
      5100 isolated strains were examined chitinase activity and biofilm formation.
      Phylogenetic analysis of these isolates based on the 16S rRNA gene sequences
      revealed that most isolates belonged to the family Aeromonadaceae, followed by
      Paenibacillaceae, Enterobacteriaceae, and Neisseriaceae. The specific activity of
      chitinase of four selected strains was higher than that of a reference strain.
      The molecular size of one chitinase produced by Andreprevotia was greater than
      that of typical bacterial chitinases. The dialyzed culture supernatant containing
      chitinases of the four strains suppressed hyphal growth of Trichoderma reesei.
      These results indicate that these four strains are good candidates for biocontrol
      agents.

PMID- 29327646
TI  - Late Blight Resistance Screening of Major Wild Swedish Solanum Species: S.
      dulcamara, S. nigrum, and S. physalifolium.
AB  - To understand the contribution of wild Solanum species to the epidemiology of
      potato late blight in Sweden, we characterized the resistance of the three
      putative alternative hosts: S. physalifolium, S. nigrum, and S. dulcamara to
      Phytophthora infestans, the causal agent of late blight. The pathogen sporulated
      in all 10 investigated S. physalifolium genotypes, suggesting susceptibility (S
      phenotype). Field-grown S. physalifolium was naturally infected but could regrow,
      though highly infected genotypes were smaller at the end of the season. In 75 S.
      nigrum genotypes, there were no symptoms (R phenotype) or a lesion restricted to
      the point of inoculation (RN phenotype), indicating resistance. In 164 S.
      dulcamara genotypes, most resistance variability was found within sibling groups.
      In addition to the three resistance phenotypes (R, RN, and S), in S. dulcamara a
      fourth new resistance phenotype (SL) was identified with lesions larger than the
      point of inoculation but without visible sporulation of the pathogen.
      Quantitative PCR confirmed P. infestans growth difference in RN, SL, and S
      phenotypes. Thus, in Sweden S. physalifolium is susceptible and could be a player
      in epidemiology. A limited role of S. dulcamara leaves in the epidemiology of
      late blight was suggested, since no major symptoms have been found in the field.

PMID- 29327647
TI  - Afrina sporoboliae sp. n. (Nematoda: Anguinidae) Associated with Sporobolus
      cryptandrus from Idaho, United States: Phylogenetic Relationships and Population
      Structure.
AB  - The dropseed gall-forming nematode, Afrina sporoboliae sp. n., is described from
      seed galls of Sporobolus cryptandrus (Poaceae: Chloridoideae: Sporobolinae)
      collected in Idaho, USA. This is the third report of an Afrina species in North
      America and the first report of this genus in a natural plant population on this
      continent. Morphological, morphometric, and molecular analyses placed this
      nematode in genus Afrina and demonstrated that it differs from Afrina
      hyparrheniae and Afrina spermophaga by having longer body and stylet lengths for
      females and males, and from Afrina wevelli by the absence of tip irregularities
      on the tails of female and presence of lips noticeably protruding beyond the body
      contour. The new species has several characters that overlap with Afrina
      tumefaciens, but differs from this species by inducing seed galls, whereas Afrina
      tumefaciens induces ovoid galls on stems, leaves, and in flower heads.
      Evolutionary relationships of Afrina sporoboliae sp. n. with other
      representatives of the family Anguinidae are presented based on analysis of the
      internal transcribed spacer (ITS)1-5.8S-ITS2 rRNA and the D2-D3 regions of the
      rRNA genes. Analysis of 270 sequences of the cox1 gene from 25 populations of
      Afrina sporoboliae sp. n. revealed seven haplotypes with sequence divergence up
      to 5%. This study did not demonstrate a significant positive relationship between
      genetic difference and geographic distance. Seed gall nematodes are important
      quarantine pests in many countries. The association of this and other seed gall
      nematodes with Rathayibacter species and their ability to serve as vectors,
      especially of R. toxicus, is of concern for U.S. agriculture.

PMID- 29327648
TI  - The Goniometer Device: Special Equipment Designed for Symmetric Mammoplasty
      Planning and Photo-Symmetry Analysis Technique.
AB  - INTRODUCTION: Preoperative planning is an essential prerequisite for the success
      of plastic surgery. In procedures such as breast reduction, freehand drawings may
      be associated with a number of challenges during the determination of axes
      vertical and parallel to the surgical site. Furthermore, many procedures involve
      subjective maneuvers, such as attempts aimed at positioning both nipples on the
      same line and transferring nipple-areola complexes in a well-matched manner. Our
      newly designed instrument, that is, the goniometer (TG), aims to ensure metric
      measurements appropriate for the axes, and it may also be used in circumstances
      that require angle measurements. Moreover, it incorporates a canal system to
      facilitate surgical designing of the area, to which the nipple-areola complex
      will be transferred. METHOD: From April 2013 to September 2015, TG device was
      used in superior pedicle breast reduction operation of 96 patients and 50 of them
      were randomly selected for the purpose of study analyses. An additional randomly
      selected 50 patients, in whom surgical planning was based on conventional
      techniques were served as controls. At postoperative 1 year, symmetry analysis
      was carried out on patient photographs. RESULTS: No partial or total necrosis
      occurred at the nipple-areola complex, and symmetrical volume and shape could be
      achieved in all cases. TG device exhibited superiority in all criteria used for
      postoperative symmetry analyses (P < .05). CONCLUSION: We believe that this
      device may effectively accelerate the planning process in various types of
      plastic and aesthetic operations and may help ensure symmetry, especially in
      reduction mammoplasty and mastopexy.

PMID- 29327649
TI  - The effect of auditory stimulus training on swimming start reaction time.
AB  - Task-specific auditory training can improve sensorimotor processing times of the
      auditory reaction time (RT). The majority of competitive swimmers do not conduct
      habitual start training with the electronic horn used to commence a race. We
      examined the effect of four week dive training interventions on RT and block time
      (BT) of 10 male adolescent swimmers (age 14.0 +/- 1.4 years): dive training with
      auditory components (speaker and electronic horn) (n = 5) and dive training
      without auditory components (n = 5). Auditory stimulus dive training
      significantly reduced swimming start RT, compared with dive training without
      auditory components (p < 0.01), with a group mean RT reduction of 13 +/- 9 ms.
      Four of the five swimmers that received auditory stimulus training showed medium
      to large effect size reductions in RT (d = 0.74; 1.32; 1.40; 1.81). No
      significant changes to swimmers' BTs were evident in either dive training
      intervention. The adolescent swimmers' results were compared against six male
      elite swimmers (age 19.8 +/- 1.0 years). The elite swimmers had significantly
      shorter BTs (p < 0.05) but no significant difference in RTs. Auditory stimulus
      dive training should be explored further as a mechanism for improving swimming
      start performance in elite swimmers who have pre-established optimal BTs.

PMID- 29327650
TI  - Transesophageal Echocardiography Use in Diagnosis and Management of Embolized
      Intravascular Foreign Bodies.
AB  - The increasing use of endovascular interventions coupled with the large number of
      published case series detailing complications attest to the likelihood that
      anesthesiologists will encounter a case of intravascular foreign body
      embolization during their careers. Transesophageal echocardiography is essential
      to the diagnosis and management of traumatic and intravascular foreign bodies
      embolized to the heart because it can identify not only the foreign body but also
      hemodynamically significant lesions to radiolucent anatomic structures prior to
      and during surgical exploration. In this case presentation, we review how
      intraoperative transesophageal echocardiography facilitated the intraoperative
      assessment and management of a post-liver transplant patient who underwent open
      surgical removal of migrated inferior vena cava stent from the right ventricle
      with concomitant tricuspid valve annuloplasty.

PMID- 29327651
TI  - A new application for the quantification of apoplastic redox radicals of plant
      roots using pre-fluorescent probe.
AB  - New application of fluorescence probe to detect apoplastic redox radicals from
      plant roots were sought. This probe can detect radicals selectively. Calibration
      curve for radicals was obtained using nitrogen monoxide as radical standard
      produced by NOC7. Apoplastic radicals released constitutively were quantified and
      the release rate was 60 MUmol L-1 h-1. Oxidative burst triggered by chitin was
      distinguished from constitutive radical release.

PMID- 29327652
TI  - Acquisition of a mental strategy to control a virtual tail via brain-computer
      interface.
AB  - The objective of the present study was to clarify the variation in and properties
      of mental images and policies used to regulate specific image selection when
      learning to control a brain-computer interface. Healthy volunteers performed a
      reaching task with a virtually generated monkey tail-like object on a computer
      monitor by regulating event-related desynchronization (ERD) on the buttock area
      of the sensorimotor cortex as recorded by electroencephalogram (EEG).
      Participants were instructed to find a free image by which the tail was well
      controlled. Seven participants frequently returned to specific images that were
      mostly unrelated to a tail, and returned to these images on the last day of
      training. The ERD levels were greater during use of those selected images versus
      when selected images were not employed. Our results suggest that individuals
      adopted a mental strategy where they imagine what would reduce the prediction
      error between the predicted and actual BCI actions.

PMID- 29327654
TI  - Delayed Reaction: The Tardy Embrace of Physical Organic Chemistry by the German
      Chemical Community.
AB  - The emergence of physical organic chemistry, which focuses on the mechanisms and
      structures of organic reactions and molecules using the tools of physical
      chemistry, was a major development in twentieth-century chemistry. It first
      flourished in the interwar period, in the UK and then in the US. Germany, by
      contrast, did not embrace the field until almost a half century later. The great
      success of classical organic chemistry, especially in synthesis, encouraged
      indifference to the new field among German chemists, as did their inductivist
      research philosophy, as enunciated by Walter Huckel's ground-breaking textbook
      (1931). This author also resisted new concepts and representations, especially
      those of the American theoretician, Linus Pauling. The arrival of the Nazi regime
      reinforced such resistance. Postwar conditions initiated a reaction against this
      conservative, nationalistic attitude, especially in the American Occupation Zone.
      Exposure to American textbooks and visiting lecturers influenced attitudes of
      younger chemists. The accompanying shift towards a more explanatory, less
      hierarchical mode of pedagogy was consonant with larger social and political
      developments.

PMID- 29327653
TI  - Preparation and in vitro and in vivo evaluation of quercetin-loaded mixed
      micelles for oral delivery.
AB  - Quercetin (QT) is a plant polyphenol with various pharmacological properties.
      However, the low water solubility limits its therapeutic efficacy. In the present
      study, QT-loaded sodium taurocholate-Pluronic P123 (QT-loaded ST/P123) mixed
      micelles were developed and characterized, and the effect of the formulation on
      improving the water solubility of QT was investigated. QT-loaded ST/P123 mixed
      micelles were prepared by thin film hydration-direct dissolution and optimized by
      uniform design. The optimal formulation possessed high drug loading (12.6%) and
      entrapment efficiency (95.9%) in small (16.20 nm) spherically-shaped micelles. A
      low critical micelle concentration indicated that the micelles were stable, and
      they showed a sustained release pattern, as determined in vitro in simulated
      gastric fluid and intestinal fluid. Pharmacokinetic evaluation showed the Cmax
      and AUC0-24 were 1.8-fold and 1.6-fold higher than the QT suspension. The present
      results indicate that QT-loaded ST/P123 micelles are potential candidates to
      improve the solubility and oral bioavailability of QT.

PMID- 29327655
TI  - Accuracy between optical and inertial motion capture systems for assessing trunk
      speed during preferred gait and transition periods.
AB  - Motion capture through inertial sensors is becoming popular, but its accuracy to
      describe kinematics during changes in walking speed is unknown. The aim of this
      study was to determine the accuracy of trunk speed extracted using an inertial
      motion system compared to a gold standard optical motion system, during steady
      walking and stationary periods. Eleven participants walked on pre-established
      paths marked on the floor. Between each lap, a 1-second stationary transition
      period at the initial position was included prior to the next lap. Resultant
      trunk speed during the walking and transition periods were extracted from an
      inertial (240 Hz sampling rate) and an optical system (120 Hz sampling rate) to
      calculate the agreement (Pearson's correlation coefficient) and relative root
      mean square errors between both systems. The agreement for the resultant trunk
      speed between the inertial system and the optical system was strong (0.67 < r <=
      0.9) for both walking and transition periods. Moreover, relative root mean square
      error during the transition periods was greater in comparison to the walking
      periods (>40% across all paths). It was concluded that trunk speed extracted from
      inertial systems have fair accuracy during walking, but the accuracy was reduced
      in the transition periods.

PMID- 29327656
TI  - NAD+/NADH homeostasis affects metabolic adaptation to hypoxia and secondary
      metabolite production in filamentous fungi.
AB  - Filamentous fungi are used to produce fermented foods, organic acids, beneficial
      secondary metabolites and various enzymes. During such processes, these fungi
      balance cellular NAD+:NADH ratios to adapt to environmental redox stimuli.
      Cellular NAD(H) status in fungal cells is a trigger of changes in metabolic
      pathways including those of glycolysis, fermentation, and the production of
      organic acids, amino acids and secondary metabolites. Under hypoxic conditions,
      high NADH:NAD+ ratios lead to the inactivation of various dehydrogenases, and the
      metabolic flow involving NAD+ is down-regulated compared with normoxic
      conditions. This review provides an overview of the metabolic mechanisms of
      filamentous fungi under hypoxic conditions that alter the cellular NADH:NAD+
      balance. We also discuss the relationship between the intracellular redox balance
      (NAD/NADH ratio) and the production of beneficial secondary metabolites that
      arise from repressing the HDAC activity of sirtuin A via Nudix hydrolase A (NdxA)
      dependent NAD+ degradation.

PMID- 29327657
TI  - Rare disease prevention and treatment: the need for a level playing field.
AB  - Pharmacogenetic tests are being used increasingly to prevent rare and potentially
      life-threatening adverse drug reactions. For many tests, however, cost
      effectiveness is hard to demonstrate, and with the exception of a few cases,
      widespread implementation remains a distant prospect. Many orphan drugs for rare
      diseases are also not cost effective but are nonetheless normally reimbursed. In
      this article, we argue that the health technology assessment of pharmacogenetic
      tests aimed to prevent rare but severe adverse drug reactions should be on a
      level playing field with orphan drugs. This is supported by a number of
      arguments, concerning the severity, rarity and iatrogenic nature of adverse drug
      reactions, the distribution of benefits and costs and societal preference towards
      prevention over treatment.

PMID- 29327658
TI  - Immunohistochemical analysis of IL-1 Receptor 1 in the discs of patients with
      temporomandibular joint dysfunction.
AB  - Objective Temporomandibular joint dysfunction (TMD) may affect a patient's
      quality of life, and one of the etiologies can be anterior disc displacement with
      reduction (ADDwR) and anterior disc displacement without reduction (ADDWoR).
      Interleukin 1 Receptor 1 (IL-1R1) is a membrane receptor that plays an important
      role on initiating immune and inflammatory response by binding the agonists
      ligands of IL-1 alpha and IL-1 beta. Therefore, the aim of this study was to
      evaluate, through immunohistochemical analysis, the association of IL-1R1 with
      TMD. Methods Thirty-nine human disc samples were collected and composed three
      different groups: ADDwR (n = 19), ADDwoR (n = 12), and control group (n = 8). The
      samples were immunostained with IL-1R1 antibody and evaluated on both quantity
      and intensity of staining. Results There was a statistically significant
      difference (p < 0.05) between the control and test groups for both quantity and
      intensity of staining. Conclusion IL1-R1 was associated with ADDwR and ADDwoR in
      TMD discs of humans.

PMID- 29327659
TI  - Stabilization of mesophilic Allochromatium vinosum cytochrome c' through specific
      mutations modeled by a thermophilic homologue.
AB  - AVCP cytochrome c' from mesophilic Allochromatium vinosum exhibits lower
      stability than a thermophilic counterpart, Hydrogenophilus thermoluteolus
      cytochrome c' (PHCP), in which the six specific amino acid residues that are not
      conserved in AVCP are responsible for its stability. Here we measured the
      stability of AVCP variants carrying these specific residues instead of the
      original AVCP ones. Among the six single AVCP variants, all of which formed a
      dimeric structure similar to that of the wild-type, three were successfully
      stabilized compared with the wild-type, while one showed lower stability than the
      wild-type. In addition, the most stabilized and destabilized AVCP variants could
      bind CO, similar to the wild-type. These results indicated that mesophilic AVCP
      could be stabilized through specific three mutations modeled by the thermophilic
      counterpart, PHCP, without changing the CO binding ability.

PMID- 29327660
TI  - Identification of 2-phenylethanol with a rose-like odor from anal sac secretions
      of the small Indian mongoose (Herpestes auropunctatus).
AB  - The small Indian mongoose (Herpestes auropunctatus) is an invasive species in
      Okinawa and Amami-Oshima, Japan. Major strategies for their eradication have been
      the use of baited traps, which suffer from decreasing efficiency with declining
      populations and the bycatch of native animals. To address these concerns,
      mongoose-specific lures are required. In this study, we aimed to identify species
      and/or sex-specific compounds from anal sac secretions of small Indian
      mongooses. Volatile compounds emitted from male and female mongoose anal sac
      secretions were analyzed by thermal desorption-gas chromatography-mass
      spectrometry. In addition to several fatty acids, 2-phenylethanol was identified
      as a minor compound, which is uncommon in mammalian secretions but a dominant
      odorant in roses. Female samples emitted higher levels of 2-phenylethanol than
      male samples did. These findings indicate that 2-phenylethanol is a female
      specific volatile compound of anal sac secretions in small Indian mongooses, and
      it may be useful as an ingredient of mongoose-specific scent lures.

PMID- 29327662
TI  - Managing Health Conditions in Older Adulthood: Barriers, Facilitators, and
      Solutions.

PMID- 29327661
TI  - Evaluations of the tongue and hyoid bone positions and pharyngeal airway
      dimensions after maxillary protraction treatment.
AB  - Objective To assess changes in the tongue and hyoid bone positions and airway
      dimensions after maxillary protraction using lateral cephalograms. Methods
      Lateral cephalograms were obtained before (C0) and after (C1) an observation
      period for untreated children with skeletal Class I malocclusion and before (T0),
      immediately after (T1), and one year after (T2) maxillary protraction in children
      with skeletal Class III malocclusion. Cephalometric measurements were compared
      between the time points in both patient groups. Results Immediately after
      maxillary protraction, the tongue moved superiorly and the nasopharyngeal and
      superior oropharyngeal airway dimensions increased. No significant changes in the
      middle or inferior oropharyngeal airway dimensions or in the hyoid bone position
      were noted after treatment. Conclusions Maxillary protraction improved tongue
      posture and modified the nasopharyngeal and superior oropharyngeal airway
      dimensions in patients with skeletal Class III malocclusion. Consequently,
      maxillary protraction may restore the intra- and extraoral balance and improve
      respiratory function.

PMID- 29327664
TI  - Farewell Editorial.

PMID- 29327665
TI  - Introductory Editorial.

PMID- 29327666
TI  - Understanding and Supporting Persons With Memory Loss and Their Families Across
      the Spectrum of Dementia.

PMID- 29327668
TI  - Impact of 3 Tesla MRI on interobserver agreement in clinically isolated syndrome:
      A MAGNIMS multicentre study.
AB  - BACKGROUND: Compared to 1.5 T, 3 T magnetic resonance imaging (MRI) increases
      signal-to-noise ratio leading to improved image quality. However, its clinical
      relevance in clinically isolated syndrome suggestive of multiple sclerosis
      remains uncertain. OBJECTIVES: The purpose of this study was to investigate how 3
      T MRI affects the agreement between raters on lesion detection and diagnosis.
      METHODS: We selected 30 patients and 10 healthy controls from our ongoing
      prospective multicentre cohort. All subjects received baseline 1.5 and 3 T brain
      and spinal cord MRI. Patients also received follow-up brain MRI at 3-6 months.
      Four experienced neuroradiologists and four less-experienced raters scored the
      number of lesions per anatomical region and determined dissemination in space and
      time (McDonald 2010). RESULTS: In controls, the mean number of lesions per rater
      was 0.16 at 1.5 T and 0.38 at 3 T ( p = 0.005). For patients, this was 4.18 and
      4.40, respectively ( p = 0.657). Inter-rater agreement on involvement per
      anatomical region and dissemination in space and time was moderate to good for
      both field strengths. 3 T slightly improved agreement between experienced raters,
      but slightly decreased agreement between less-experienced raters. CONCLUSION:
      Overall, the interobserver agreement was moderate to good. 3 T appears to improve
      the reading for experienced readers, underlining the benefit of additional
      training.

PMID- 29327669
TI  - Advanced 3D Models Cultured to Investigate Mesenchymal Stromal Cells of the Human
      Dental Follicle.
AB  - The human dental follicle (hDF) contains the developing tooth and is involved in
      regulating tooth maturation and eruption. To investigate the mesenchymal stromal
      cells of the dental follicle, 2 three-dimensional (3D) culture models were used,
      based on a dynamic bioreactor: the Rotary Cell Culture System (RCCSTM) and the 3D
      culture of precursor cells isolated from follicular tissue (human dental follicle
      cells [hDFCs]). The hDFCs were obtained from impacted third molars of 20
      patients. Two 3D culture models were tested. In the first model, intact hDF
      explants were cultured in 3D conditions, preserving the original tissue
      architecture; they were studied using histomorphological and molecular analyses.
      The second model involved the 3D culture of hDFCs, which were characterized to
      evaluate their multipotency in terms of differentiation capability. Of the
      biomarkers known to characterize hDFCs, hDF precursors were selected for our
      study. The immunophenotype and in situ immunocytochemistry were evaluated for
      markers CD44, CD90, CD146, CD105, CD31, CD34, and CD45 Ag. The results show that
      the conditions provided by the RCCS preserve the original organizational
      architecture of the cells. The 3D conditions of the model enhanced
      differentiation in response to adipogenic, osteogenic, and chondrogenic inductive
      growth media. The immunophenotype and the immunocytochemistry showed generally
      high expression of CD90, CD44, and CD105, while CD146 expression was more
      restricted to ~30% of cells. No expression was observed for CD31, CD34, and CD45
      Ags. Two 3D tissue- and cell-based ex vivo models of the hDF supported the long
      term maintenance of hDF-specific cell phenotypes and their ability to
      recapitulate typical cellular differentiation states. As such, these ex vivo
      models could be used to study the physiopathology of human odontogenesis. In
      addition, in a therapeutic context, they could be used to examine the role of
      specific chemical signals (e.g., new therapeutic agents) in the processes of
      dental tissue repair and regeneration.

PMID- 29327670
TI  - Identification of undesirable white-colony-forming yeasts appeared on the surface
      of Japanese kimchi.
AB  - To identify yeasts involved in white-colony formation on Japanese commercial
      kimchi products, three types of kimchi were prepared and fermented at four
      different temperatures. At 4  degrees C, yeast colonies did not appear until 35
      days, while more rapid white-colony formation occurred at higher temperatures
      (10, 15, and 25  degrees C). Combination of PCR-DGGE and direct isolation of
      yeasts from white colonies revealed that Kazachstania exigua and K. pseudohumilis
      were responsible for the white-colony formation. Inoculation of the isolated
      Kazachstania strains into fresh kimchi successfully reproduced white-colony
      formation at 15  degrees C but not at 4  degrees C. Growth experiments in liquid
      medium revealed that Kazachstania spp. grew fast at 15  degrees C even in the
      presence of acidulants, which are commonly added to Japanese kimchi products for
      prevention of yeast growth. These results suggest that white-colony formation on
      Japanese kimchi is caused by the genus Kazachstania, and that one of important
      factors determining white-colony formation is its fermentation temperature.

PMID- 29327672
TI  - Linear epitopes in African swine fever virus p72 recognized by monoclonal
      antibodies prepared against baculovirus-expressed antigen.
AB  - Protein p72 is the major capsid protein of African swine fever virus (ASFV) and
      is an important target for test and vaccine development. Monoclonal antibodies
      (mAbs) were prepared against a recombinant antigenic fragment, from amino acid
      (aa) 20-303, expressed in baculovirus. A total of 29 mAbs were recovered and
      tested by immunofluorescent antibody (IFA) staining on ASFV Lisbon-infected Vero
      cells. Six antibodies were IFA-positive and selected for further
      characterization. Epitope mapping was performed against overlapping polypeptides
      expressed in E. coli and oligopeptides. Based on oligopeptide recognition, the
      mAbs were divided into 4 groups: mAb 85 (aa 165-171); mAbs 65-3 and 6H9-1 (aa 265
      280); mAbs 8F7-3 and 23 (aa 280-294); and mAb 4A4 (aa 290-303). All mAbs were
      located within a highly conserved region in p72. This panel of antibodies
      provides the opportunity to develop new assays for the detection of ASFV antibody
      and antigen.

PMID- 29327673
TI  - Evaluation of the electromyographic fatigue of the masseter and temporalis
      muscles in individuals with osteoporosis.
AB  - Objectives The objective of this study was to evaluate the electromyographic
      fatigue of the masseter and temporalis muscles in individuals with and without
      osteoporosis. Methods Median frequency of the initial, mid, and final periods of
      the electromyographic signal in the 33 subjects with osteoporosis (OG) and 33
      subjects without osteoporosis [control (CG)] was analyzed. Results OG showed a
      decrease in median frequency along the electromyographic signal, with a
      significant difference for the right masseter: initial vs. mid periods, initial
      vs. final periods; left masseter: initial vs. final periods; temporal (right and
      left): initial vs. mid periods, initial vs. final periods, and mid vs. final
      periods. Percentage comparison of median frequency between the initial and mid
      periods and between initial and final periods in the OG showed a significant
      difference in the masticatory muscles. Discussion The findings suggest that
      osteoporosis is associated with changes in the function of masticatory muscles,
      especially when measured by electromyographic fatigue.

PMID- 29327674
TI  - Insoluble Microenvironment Facilitating the Generation and Maintenance of
      Pluripotency.
AB  - Induced pluripotent stem cells (iPSCs) hold enormous potential as a tool to
      generate cells for tissue engineering and regenerative medicine. Since the
      initial report of iPSCs in 2006, many different methods have been developed to
      enhance the safety and efficiency of this technology. Recent studies indicate
      that the extracellular signals can promote the production of iPSCs, and even
      replace the Yamanaka factors. Noticeably, abundant evidences suggest that the
      insoluble microenvironment, including the culture substrate and neighboring
      cells, directly regulates the expression of core pluripotency genes and the
      epigenetic modification of the chromatins, hence, impacts the reprogramming
      dynamics. These studies provide new strategies for developing safer and more
      efficient method for iPSC generation. In this review, we examine the publications
      addressing the insoluble extracellular microenvironment that boosts iPSC
      generation and self-renewal. We also discuss cell adhesion-mediated molecular
      mechanisms, through which the insoluble extracellular cues interplay with
      reprogramming.

PMID- 29327675
TI  - The relationship between oral tori and bite force.
AB  - Objective The relationship between bite force and torus palatinus or mandibularis
      remains to be explained. The major aim of this study was to determine the
      correlation between bite force and oral tori. Methods The bite force of 345
      patients was measured with a bite force recorder; impressions of the shape and
      size of the oral tori were taken on plaster models prior to orthodontic
      treatments. Subsequently, the relationship between oral tori and bite force was
      analyzed. Results The size, shape, and incidence of torus palatinus was not
      significantly correlated with bite force. However, the size of torus mandibularis
      increased significantly in proportion to the bite force (p = 0.020). The
      occurrence of different types of oral tori was not correlated with the bite
      force. Discussion The size of torus mandibularis provides information about bite
      force and can thus be used to clinically assess occlusal stress.

PMID- 29327676
TI  - Physiological responses to taste signals of functional food components.
AB  - The functions of food have three categories: nutrition, palatability, and
      bioregulation. As the onset of lifestyle-related diseases has increased, many
      people have shown interest in functional foods that are beneficial to
      bioregulation. We believe that functional foods should be highly palatable for
      increased acceptance from consumers. In order to design functional foods with a
      high palatability, we have investigated about the palatability, especially in
      relation to the taste of food. In this review, we discuss (1) the identification
      of taste receptors that respond to functional food components; (2) an analysis of
      the peripheral taste transduction system; and (3) the investigation of the
      relationship between physiological functions and taste signals.

PMID- 29327678
TI  - Polymorphism observed in mitochondrial genes of red flour beetle, Tribolium
      castaneum (Coleoptera: Tenebrionidae) of different origin in laboratory cultures.
AB  - Tribolium castaneum, a pest of stored grain, has a uniform morphology, preventing
      the visual identification of strains from different areas. Polymorphisms in the
      nucleotide sequences of the mitochondrial genes of this species were examined,
      and combined into seven haplotypes among the test insect specimens originating
      from Japan, Thailand, and Canada. These results suggested the potential for
      geographical differentiation.

PMID- 29327671
TI  - Tissue-Engineered Heart Valves: A Call for Mechanistic Studies.
AB  - Heart valve disease carries a substantial risk of morbidity and mortality.
      Outcomes are significantly improved by valve replacement, but currently available
      mechanical and biological replacement valves are associated with complications of
      their own. Mechanical valves have a high rate of thromboembolism and require
      lifelong anticoagulation. Biological prosthetic valves have a much shorter
      lifespan, and they are prone to tearing and degradation. Both types of valves
      lack the capacity for growth, making them particularly problematic in pediatric
      patients. Tissue engineering has the potential to overcome these challenges by
      creating a neovalve composed of native tissue that is capable of growth and
      remodeling. The first tissue-engineered heart valve (TEHV) was created more than
      20 years ago in an ovine model, and the technology has been advanced to clinical
      trials in the intervening decades. Some TEHVs have had clinical success, whereas
      others have failed, with structural degeneration resulting in patient deaths. The
      etiologies of these complications are poorly understood because much of the
      research in this field has been performed in large animals and humans, and,
      therefore, there are few studies of the mechanisms of neotissue formation. This
      review examines the need for a TEHV to treat pediatric patients with valve
      disease, the history of TEHVs, and a future that would benefit from extension of
      the reverse translational trend in this field to include small animal studies.

PMID- 29327677
TI  - Autologous Smooth Muscle Progenitor Cells Enhance Regeneration of Tissue
      Engineered Bladder.
AB  - Tissue engineering techniques provide a great potential to de novo construct a
      histological bladder. Smooth muscle regeneration is extremely important for the
      functional recovery of engineered neobladder. However, many challenges remain for
      the use of bladder smooth muscle cells (SMCs) as the cell sources. Recent
      evidences showed that smooth muscle progenitor cells (SPCs) in the peripheral
      blood have the capacity of differentiating into SMCs, while their use for bladder
      regeneration has not yet been reported. The aim of our study was to investigate
      the effect and mechanism of autologous SPCs on bladder regeneration in a rabbit
      model. In this study, autologous SPCs were isolated and cultured from the
      peripheral blood, labeled with CM-DiI, and then seeded into a porcine bladder
      acellular matrix (BAM) to construct a SPC-BAM complex, which was finally
      implanted to substitute the partial bladder with an equivalent size. In the
      results, SPCs demonstrated the phenotype of stem/progenitor cells, expressed SMs
      markers (alpha-smooth muscle actin [alpha-SMA], desmin, calponin, SM22alpha, and
      smooth muscle myosin heavy chain [SMMHC]), and displayed carbachol-induced
      contraction. Compared with cell-free BAM, the SPC-BAM was able to improve
      histological regeneration (smooth muscle regeneration, vascularization, and nerve
      formation) and functional recovery (urodynamic function and smooth muscle
      contraction) of the engineered neobladder. Cell tracing indicated that seeded
      SPCs could survive and directly integrated into the regenerated neobladder. In
      addition, SPCs could also promote proliferation and migration of rabbit bladder
      SMCs through the paracrine platelet-derived growth factor-BB (PDGF-BB). In
      conclusion, our study first demonstrated that SPCs from the peripheral blood
      could enhance histological regeneration and functional recovery of the tissue
      engineered neobladder through both the direct integration and indirect paracrine
      effect, supporting the use of SPCs as the cell sources for tissue engineering of
      the bladder.

PMID- 29327679
TI  - Natural and Artificial Strategies To Control the Conjugative Transmission of
      Plasmids.
AB  - Conjugative plasmids are the main carriers of transmissible antibiotic resistance
      (AbR) genes. For that reason, strategies to control plasmid transmission have
      been proposed as potential solutions to prevent AbR dissemination. Natural
      mechanisms that bacteria employ as defense barriers against invading genomes,
      such as restriction-modification or CRISPR-Cas systems, could be exploited to
      control conjugation. Besides, conjugative plasmids themselves display mechanisms
      to minimize their associated burden or to compete with related or unrelated
      plasmids. Thus, FinOP systems, composed of FinO repressor protein and FinP
      antisense RNA, aid plasmids to regulate their own transfer; exclusion systems
      avoid conjugative transfer of related plasmids to the same recipient bacteria;
      and fertility inhibition systems block transmission of unrelated plasmids from
      the same donor cell. Artificial strategies have also been designed to control
      bacterial conjugation. For instance, intrabodies against R388 relaxase expressed
      in recipient cells inhibit plasmid R388 conjugative transfer; pIII protein of
      bacteriophage M13 inhibits plasmid F transmission by obstructing conjugative
      pili; and unsaturated fatty acids prevent transfer of clinically relevant
      plasmids in different hosts, promoting plasmid extinction in bacterial
      populations. Overall, a number of exogenous and endogenous factors have an effect
      on the sophisticated process of bacterial conjugation. This review puts them
      together in an effort to offer a wide picture and inform research to control
      plasmid transmission, focusing on Gram-negative bacteria.

PMID- 29327680
TI  - Mechanisms of Bacterial Resistance to Antimicrobial Agents.
AB  - During the past decades resistance to virtually all antimicrobial agents has been
      observed in bacteria of animal origin. This chapter describes in detail the
      mechanisms so far encountered for the various classes of antimicrobial agents.
      The main mechanisms include enzymatic inactivation by either disintegration or
      chemical modification of antimicrobial agents, reduced intracellular accumulation
      by either decreased influx or increased efflux of antimicrobial agents, and
      modifications at the cellular target sites (i.e., mutational changes, chemical
      modification, protection, or even replacement of the target sites). Often several
      mechanisms interact to enhance bacterial resistance to antimicrobial agents. This
      is a completely revised version of the corresponding chapter in the book
      Antimicrobial Resistance in Bacteria of Animal Origin published in 2006. New
      sections have been added for oxazolidinones, polypeptides, mupirocin, ansamycins,
      fosfomycin, fusidic acid, and streptomycins, and the chapters for the remaining
      classes of antimicrobial agents have been completely updated to cover the
      advances in knowledge gained since 2006.

PMID- 29327681
TI  - Updated National Comprehensive Cancer Network guidelines for treatment of head
      and neck cancers 2010-2017.
AB  - INTRODUCTION: The diagnostic and therapeutic recommendations have been changing
      over the years to improve treatment outcomes and quality of life of Head and Neck
      Cancer (HNC) patients. AIM: The aim of this study was to present currently
      recommended Head and Neck Cancer treatment guidelines based on the literature
      review with particular emphasis on novel approaches the NCCN algorithms. MATERIAL
      AND METHODS: The review of literature covering articles published in the last
      five years and pointing out essential changes in HNC treatment regarding evidence
      based medicine. The study focused on the analysis of novel approaches for the
      particular primaries, the implementation of biological therapies and personalized
      cancer therapies. RESULTS: Updates in the oncological NCCN guidelines for all ENT
      primaries except major salivary glands and subglottis are based on knowledge
      derived from the basic sciences, clinical trials and the best evidence available
      currently. The latest recommendations emphasize value of biological therapies
      use.

PMID- 29327682
TI  - Analysis of implementiation of 4th Head and Neck Cancer Awareness Week in
      Department of Otolaryngology in Miedzyleski Hospital in Warsaw.
AB  - INTRODUCTION: The aim of the study was to analyze the profile of patients
      applying for free preventive examinations within The Forth European Head an Neck
      Cancer (HNC) Awareness Week in the Department of Otorhynolaryngology in
      Miedzyleski Hospital in Warsaw (ORL MSS). MATERIAL AND METHODS: A media campaign
      was designed to inform HNC risk patients about the opportunity to receive free
      preventive examinations in ORL MSS. 225 patients were enrolled to the study.
      Patient age ranged from 26 to 92 (average 63 years). Women accounted for 66%
      (149) and males 34% (76). Each patient completed a questionnaire assessing risk
      factors for HNC, including reported symptoms and lifestyle. ENT examination was
      performed. Some patients were referred for further diagnostics and treatment.
      RESULTS: The following HNC risk factors connected with lifestyle were found:
      nicotine in 22%, alcohol in more than once a week in 12%, oral sex in 17%,
      multiple sexual partners in 10%, rare dental tests in 24%, prosthetic
      restorations in 45%. The symptom that most often prompted patients to participate
      in the HNC prevention week was chronic hoarseness (64%) of people, dry mouth
      (39%), swallowing (37%), nasal obstruction (6%), neck tumour (5%). One per every
      five patients was referred to further diagnostics: imaging screening 7% (15
      persons), fiber optic examination 11% (25 persons), the excision of the lesion 8%
      (18 persons). 17 patients were referred for further oncological treatment, of
      which 13 had benign tumors and 4 had malignant tumors. CONCLUSIONS: The HNC
      Awareness Program increases public consciousness and should systematically
      includes people with risk factors. The introduction of the Program in the ORL
      Department has made possible to detect and treat cancer in early stages in 7.5%
      of those who applied for the program. The use of adequate diagnostics and
      treatment requires, however, adequate financial resources and systemic solutions.

PMID- 29327683
TI  - Clinical manifestation of malignant lymphomas of the head and neck region.
AB  - INTRODUCTION: Malignant lymphoma (ML) is a neoplasm caused by clonal expansion of
      undifferentiated B, T and NK-lymphoid cells. WHO classification divides lymphomas
      into two main types, i.e. Hodgkin lymphoma (HL), and non-Hodgkin lymphoma (NHL),
      with numerous subtypes. The majority of MLs are localized in lymph nodes, but
      extranodal locations are also possible. MLs represent approximately 3-5% of all
      malignant neoplasms in Poland, but their incidence has been increasing in recent
      years, especially in young patients. The objective of the study was to evaluate
      clinical manifestations and diagnostic process in patients with malignant
      lymphomas of the head and neck region as diagnosed in the Department of
      Otorhinolaryngology of the Medical University of Lodz in years 2013-2017.
      MATERIAL AND METHOD: 30 patients diagnosed with malignant lymphomas of the head
      and neck region at the Departbadament of Otorhinolaryngology of the Medical
      University of Lodz in 2013-2017. RESULTS: The study group consisted of 8 cases of
      nodal lymphomas and 22 cases of extranodal lymphomas. In 29 cases B-cell
      lymphomas were diagnosed. The most common symptoms included lymphadenopathy or
      neck tumor. Other symptoms were associated with the location of tumors in
      particular body organs. The diagnosis was based on histopathological examination
      of biopsy (needle or surgical) samples. CONCLUSION: Malignant lymphomas should be
      taken into account during differential diagnosis of the tumor or lymphadenopathy
      of the neck. The diagnosis is difficult because of the nonspecificity of symptoms
      and the need for interdisciplinary cooperation of many specialists.

PMID- 29327684
TI  - Diagnosis and treatment of nasal and paranasal inverted papillomas - epidemiology
      and own experience.
AB  - INTRODUCTION: The aim of this study was to analyse the occurrence of inverted
      papillomas of the nose and paranasal sinuses in patients that underwent
      endoscopic sinus surgery in our department. MATERIAL AND METHODS: Between 2006
      and 2016, 3,574 patients underwent surgery due to paranasal sinus diseases.
      Patients were qualified for surgery based on medical history, computed
      tomography, and laboratory tests. Data were gathered from medical files, and they
      included age, sex, and histopathological diagnosis. RESULTS: Among 3,574 patients
      that underwent surgery due to chronic inflammatory changes, on histopathology,
      inverted papillomas were diagnosed in 80 patients, including 31 women (38.75%)
      and 49 men (61.25%). Most patients were aged 60-70 years (women, 12.5%; men, 15%)
      or 50-60 years (women, 5%; men, 21.25%). Between 2006 and 2016, the number of
      surgeries ranged from 264 (7.38%) in 2013 to 355 (9.93%) in 2016, and the number
      of inverted papillomas ranged from 4 in 2007 and 2015 (1.23%) to 12 in 2014
      (3.87%). Over the last 4 years of the study period, the incidence of inverted
      papillomas increased. CONCLUSIONS: Among 3,574 patients operated on due to
      chronic inflammatory changes, on histopathology, inverted papillomas were
      diagnosed in 80 cases (2.23%); thus, all patients qualified for endoscopic
      surgery due to inflammatory or hypertrophic changes should undergo rhino
      fiberoscopy. Recurrence of inverted papillomas was observed in 17.50%, typically
      in patients with nasal polyps that co-occurred with inverted papillomas. We
      regard rhino-fiberoscopy as the most valuable method for detecting tumour
      recurrence in patients after surgery for inverted papillomas.

PMID- 29327685
TI  - The role of pepsin in the laryngopharyngeal reflux.
AB  - Laryngopharyngeal reflux (LPR) is a common defect among laryngological and
      phoniatric patients. Although LPR is categorized as a superficial
      gastroesophageal reflux disease (GERD), differential diagnosis should treat these
      two diseases separately. LPR symptoms can be assessed in the interview using as a
      tool the reflux symptom index (RSI). In addition, changes in the larynx that
      occur during LPR might be seen during laryngoscopy and classified according to
      the reflux finding score (RFS). One of the main mucosal irritants in LPR is
      pepsin which digests proteins and impairs the functions of the upper respiratory
      tract cells by affecting carbonate anhydrase (CAIII) and the Sep 70 protein.
      Pepsin initiates inflammatory changes within the larynx, nasopharynx and nasal
      cavity. The use of pepsin detection in upper and lower throat secretions is a new
      direction in LPR diagnostics.

PMID- 29327686
TI  - Severity of dysphonia in patients during first days after iatrogenic injury.
AB  - INTRODUCTION: The most common cause of vocal fold paralysis (VFP) is iatrogenic
      injury. Patients with symptoms of VFP present to the specialist after a couple of
      weeks or even months since the onset of symptoms. In the literature, the data
      regarding speech impairment during the first days after a iatrogenic injury is
      lacking. AIM: to evaluate the quality of voice during first days of vocal fold
      paralysis following a iatrogenic injury. MATERIALS AND METHODS: Twenty-five
      patients with iatrogenic vocal fold paralysis who presented for phoniatric
      consultation at the Department of Otolaryngology of the Medical University of
      Warsaw between May 2015 and December 2016 were enrolled in the study. The
      patients were examined 1-2 days since the onset of speech deterioration. In all
      patients, laryngeal videolaryngostroboscopy was performed, based on which the
      following were assessed: vocal fold mobility, mucosal wave, phonation closure,
      simultaneity and amplitude of vocal fold vibration. Acoustic analysis was
      performed, and the following acoustic parameters were evaluated: DSI, F0,
      Shimmer, Jitter, NHR. Also, the maximal phonation time of [a] sound (MPT a) was
      assessed and the voice perception analysis with the GRBAS scale was performed.
      The patients self-evaluated their voice using a 10-point VAS scale. RESULTS:
      Based on the videolaryngostroboscopy, phonatory insufficiency and asymmetrical
      vocal fold vibration were observed. On perception assessment with GRBAS scale, we
      noticed slight to mild degree hoarseness, breathiness of sound and weakened
      voice. In majority of patients, the maximal phonation time of [a] sound was
      significantly reduced. All patients showed abnormal acoustic parameters. None of
      them rated their voice as perfectly normal on VAS scale.

PMID- 29327687
TI  - Effect of speechreading in presbycusis: Do we have a third ear?
AB  - INTRODUCTION: Evidence regarding the effect of speechreading is lacking in age
      related hearing loss (presbycusis). Thus, in individuals with presbycusis, this
      study determined whether speechreading would improve word intelligibility.
      Moreover, the study investigated the effect of speechreading on word
      intelligibility depending on hearing impairment severity. MATERIALS AND METHODS:
      This analytical, cross-sectional study involved two groups of individuals aged >
      65 years that were enrolled by convenience sampling: 29 individuals with
      bilateral sensorineural hearing loss compatible with presbycusis (n=58 ears; mean
      age, 74.1+/-9.4 years) and 10 controls with at-most-mild hearing loss (n=58 ears;
      mean age, 73.8+/-8.5 years). All participants underwent a comprehensive medical
      and audiological evaluation, which included speech audiometry with and without
      observation of the audiologist's face, i.e. speechreading. Within each group, the
      effect of speechreading was determined as a change in the speech reception
      threshold. For all statistical analyses, p < 0.05 was considered significant.
      RESULTS: Both in individuals with presbycusis and controls, speechreading
      significantly improved speech discrimination (p<.001<.05); however, compared to
      controls, this effect of speechreading on speech discrimination was more
      pronounced in individuals with presbycusis (p<.001). DISCUSSION: Individuals with
      presbycusis or hearing impairment displayed improved spoken-word intelligibility
      when spoken-word recognition was coupled with speechreading. Thus, speechreading
      may serve as a "third ear".

PMID- 29327688
TI  - Empirical optimization of DFT  +  U and HSE for the band structure of ZnO.
AB  - ZnO is a well-known wide band gap semiconductor with promising potential for
      applications in optoelectronics, transparent electronics, and spintronics.
      Computational simulations based on the density functional theory (DFT) play an
      important role in the research of ZnO, but the standard functionals, like Perdew
      Burke-Erzenhof, result in largely underestimated values of the band gap and the
      binding energies of the Zn3d electrons. Methods like DFT  +  U and hybrid
      functionals are meant to remedy the weaknesses of plain DFT. However, both
      methods are not parameter-free. Direct comparison with experimental data is the
      best way to optimize the computational parameters. X-ray photoemission
      spectroscopy (XPS) is commonly considered as a benchmark for the computed
      electronic densities of states. In this work, both DFT  +  U and HSE methods were
      parametrized to fit almost exactly the binding energies of electrons in ZnO
      obtained by XPS. The optimized parameterizations of DFT  +  U and HSE lead to
      significantly worse results in reproducing the ion-clamped static dielectric
      tensor, compared to standard high-level calculations, including GW, which in turn
      yield a perfect match for the dielectric tensor. The failure of our XPS-based
      optimization reveals the fact that XPS does not report the ground state
      electronic structure for ZnO and should not be used for benchmarking ground state
      electronic structure calculations.

PMID- 29327689
TI  - Global spectral graph wavelet signature for surface analysis of carpal bones.
AB  - Quantitative shape comparison is a fundamental problem in computer vision,
      geometry processing and medical imaging. In this paper, we present a spectral
      graph wavelet approach for shape analysis of carpal bones of the human wrist. We
      employ spectral graph wavelets to represent the cortical surface of a carpal bone
      via the spectral geometric analysis of the Laplace-Beltrami operator in the
      discrete domain. We propose global spectral graph wavelet (GSGW) descriptor that
      is isometric invariant, efficient to compute, and combines the advantages of both
      low-pass and band-pass filters. We perform experiments on shapes of the carpal
      bones of ten women and ten men from a publicly-available database of wrist bones.
      Using one-way multivariate analysis of variance (MANOVA) and permutation testing,
      we show through extensive experiments that the proposed GSGW framework gives a
      much better performance compared to the global point signature embedding approach
      for comparing shapes of the carpal bones across populations.

PMID- 29327690
TI  - Laser-direct writing by two-photon polymerization of 3D honeycomb-like structures
      for bone regeneration.
AB  - A major limitation of existing 3D implantable structures for bone tissue
      engineering is that most of the cells rapidly attach on the outer edges of the
      structure, restricting the cells penetration into the inner parts and causing the
      formation of a necrotic core. Furthermore, these structures generally possess a
      random spatial arrangement and do not preserve the isotropy on the whole volume.
      Here, we report on the fabrication and testing of an innovative 3D hierarchical,
      honeycomb-like structure (HS), with reproducible and isotropic arhitecture, that
      allows in 'volume' migration of osteoblasts. In particular, we demonstrate the
      possibility to control the 3D spatial cells growth inside these complex
      architectures by adjusting the free spaces inside the structures. The structures
      were made of vertical microtubes arranged in a mulitlayered configuration,
      fabricated via laser direct writing by two photons polymerization of the IP-L780
      photopolymer. In vitro tests performed in MG-63 osteoblast-like cells
      demonstrated that the cells migration inside the 3D structures is conducted by
      the separation space between the microtubes layers. Specifically, for layers
      separation between 2 and 10 MUm, the cells gradually penetrated between the
      microtubes. Furthermore, these structures induced the strongest cells osteogenic
      differentiation and mineralization, with ALP activity 1.5 times stronger, amount
      of calcified minerals 1.3 times higher and osteocalcin secretion increased by 2.3
      times compared to the other structures. On the opposite, for layers separation
      less than 2 MUm and above 10 MUm, the cells were not able to make
      interconnections and exhibited poor mineralization ability.

PMID- 29327691
TI  - Fermi-level tuning of the Dirac surface state in (Bi<sub>1
      <i>x</i></sub>Sb<sub><i>x</i></sub>)<sub>2</sub>Se<sub>3</sub> thin films.
AB  - We report on the electronic states and the transport properties of three
      dimensional topological insulator (Bi<sub>1
      <i>x</i></sub>Sb<sub><i>x</i></sub>)<sub>2</sub>Se<sub>3</sub> ternary alloy thin
      films grown on an isostructural Bi<sub>2</sub>Se<sub>3</sub> buffer layer on InP
      substrates. By angle-resolved photoemission spectroscopy, we clearly detected
      Dirac surface states with a large bulk band gap of 0.2 - 0.3 eV in the (Bi<sub>1
      <i>x</i></sub>Sb<sub><i>x</i></sub>)<sub>2</sub>Se<sub>3</sub> film with <i>x</i>
      = 0.70. In addition, we observed by Hall effect measurements that the dominant
      charge carrier converts from electron (n-type) to hole (p-type) at around
      <i>x</i> = 0.7, indicating that the Fermi level can be controlled across the
      Dirac point. Indeed, the carrier transport was shown to be governed by Dirac
      surface state in 0.63 <= <i>x</i> <= 0.75.These features suggest that Fermi-level
      tunable (Bi<sub>1-<i>x</i></sub>Sb<sub><i>x</i></sub>)<sub>2</sub>Se<sub>3</sub>
      based heterostructures provide a platform for extracting exotic topological
      phenomena.

PMID- 29327693
TI  - Direct determination of k Q factors for cylindrical and plane-parallel ionization
      chambers in high-energy electron beams from 6 MeV to 20 MeV.
AB  - For the ionometric determination of the absorbed dose to water, D w, in high
      energy electron beams from a clinical accelerator, beam quality dependent
      correction factors, k Q, are required. By using a water calorimeter, these
      factors can be determined experimentally and potentially with lower standard
      uncertainties than those of the calculated k Q factors, which are tabulated in
      various dosimetry protocols. However, one of the challenges of water calorimetry
      in electron beams is the small measurement depths in water, together with the
      steep dose gradients present especially at lower energies. In this investigation,
      water calorimetry was implemented in electron beams to determine k Q factors for
      different types of cylindrical and plane-parallel ionization chambers (NE2561,
      NE2571, FC65-G, TM34001) in 10 cm  *  10 cm electron beams from 6 MeV to 20 MeV
      (corresponding beam quality index R 50 ranging from 1.9 cm to 7.5 cm). The
      measurements were carried out using the linear accelerator facility of the
      Physikalisch-Technische Bundesanstalt. Relative standard uncertainties for the k
      Q factors between 0.50% for the 20 MeV beam and 0.75% for the 6 MeV beam were
      achieved. For electron energies above 8 MeV, general agreement was found between
      the relative electron energy dependencies of the k Q factors measured and those
      derived from the AAPM TG-51 protocol and recent Monte Carlo-based studies, as
      well as those from other experimental investigations. However, towards lower
      energies, discrepancies of up to 2.0% occurred for the k Q factors of the TM34001
      and the NE2571 chamber.

PMID- 29327692
TI  - A PET reconstruction formulation that enforces non-negativity in projection space
      for bias reduction in Y-90 imaging.
AB  - Most existing PET image reconstruction methods impose a nonnegativity constraint
      in the image domain that is natural physically, but can lead to biased
      reconstructions. This bias is particularly problematic for Y-90 PET because of
      the low probability positron production and high random coincidence fraction.
      This paper investigates a new PET reconstruction formulation that enforces
      nonnegativity of the projections instead of the voxel values. This formulation
      allows some negative voxel values, thereby potentially reducing bias. Unlike the
      previously reported NEG-ML approach that modifies the Poisson log-likelihood to
      allow negative values, the new formulation retains the classical Poisson
      statistical model. To relax the non-negativity constraint embedded in the
      standard methods for PET reconstruction, we used an alternating direction method
      of multipliers (ADMM). Because choice of ADMM parameters can greatly influence
      convergence rate, we applied an automatic parameter selection method to improve
      the convergence speed. We investigated the methods using lung to liver slices of
      XCAT phantom. We simulated low true coincidence count-rates with high random
      fractions corresponding to the typical values from patient imaging in Y-90
      microsphere radioembolization. We compared our new methods with standard
      reconstruction algorithms and NEG-ML and a regularized version thereof. Both our
      new method and NEG-ML allow more accurate quantification in all volumes of
      interest while yielding lower noise than the standard method. The performance of
      NEG-ML can degrade when its user-defined parameter is tuned poorly, while the
      proposed algorithm is robust to any count level without requiring parameter
      tuning.

PMID- 29327694
TI  - Electronic structure of Fe1.08Te bulk crystals and epitaxial FeTe thin films on
      Bi2Te3.
AB  - The electronic structure of thin films of FeTe grown on Bi2Te3 is investigated
      using angle-resolved photoemission spectroscopy, scanning tunneling microscopy
      and first principles calculations. As a comparison, data from cleaved bulk
      Fe1.08Te taken under the same experimental conditions is also presented. Due to
      the substrate and thin film symmetry, FeTe thin films grow on Bi2Te3 in three
      domains, rotated by 0 degrees , 120 degrees , and 240 degrees . This results in a
      superposition of photoemission intensity from the domains, complicating the
      analysis. However, by combining bulk and thin film data, it is possible to partly
      disentangle the contributions from three domains. We find a close similarity
      between thin film and bulk electronic structure and an overall good agreement
      with first principles calculations, assuming a p-doping shift of 65 meV for the
      bulk and a renormalization factor of around two. By tracking the change of
      substrate electronic structure upon film growth, we find indications of an
      electron transfer from the FeTe film to the substrate. No significant change of
      the film's electronic structure or doping is observed when alkali atoms are dosed
      onto the surface. This is ascribed to the film's high density of states at the
      Fermi energy. This behavior is also supported by the ab initio calculations.

PMID- 29327695
TI  - Multiple inflamed cutaneous nodules in an elderly female.

PMID- 29327697
TI  - An unusual early onset of lentigo maligna in the fourth decade of life.

PMID- 29327696
TI  - Sarcomatoid lung carcinoma presenting as alopecia neoplastica.

PMID- 29327698
TI  - Eruptive pseudoangiomatosis - cherry angiomas with perilesional halo.
AB  - Eruptive pseudoangiomatosis is a rare viral exanthem characterized by acute onset
      of hemangiomata-like lesions, however, histological findings are distinct from
      that of true angiomas. This entity has been reported from Europe, North America,
      Japan, and Korea till date. Here, we report 12 cases of eruptive
      pseudoangiomatosis from a tertiary care hospital in Punjab.

PMID- 29327699
TI  - Nail changes in autoimmune blistering disorders: A case-control study.
AB  - Background: Pemphigus and pemphigoid disorders produce blistering cutaneous
      lesions. Earlier case reports state that nail involvement is uncommon in these
      autoimmune blistering disorders. Aims and Objectives: To study nail changes in
      autoimmune blistering disorders. Methods: A case-control study was conducted
      where 40 cases and 40 controls were evaluated for nail changes. Results: Nail
      changes were seen in 72.5% of cases and 17.5% of controls. The most common nail
      findings were paronychia and onychorrhexis. Limitations: Small sample size; short
      study duration; nail biopsy could not be done. Conclusion: Our findings indicate
      that the inflammatory nature of the blistering cutaneous disease is often
      reflected conspicuously in the nails.

PMID- 29327700
TI  - Disseminated cutaneous fusariosis in human immunodeficiency virus-infected
      patient and dramatic response with oral itraconazole.
AB  - Fusarium species are known to cause disseminated cutaneous lesions in
      immunocompromised patients. Some cases of fusariosis are reported in patients
      infected with the human immunodeficiency virus. There are two reports in such
      patients with systemic comorbidities like lymphoma, neutropenia and infective
      port-a-catheter. Another reported patient had systemic fusariosis, without skin
      involvement. Diagnosis and treatment of cutaneous fusariosis is difficult and
      resistance to antifungals is a problem. Our patient was at an advanced human
      immunodeficiency virus infection stage with disseminated cutaneous fusariosis,
      without any systemic involvement, who responded completely to oral itraconazole.

PMID- 29327701
TI  - Distribution of killer immunoglobulin-like receptor genes in HIV infected long
      term non-progressors from Mumbai, India.
AB  - Background: Few reports suggest the association of killer immunoglobulin-like
      receptors of natural killer cells with human immunodeficiency virus infection.
      India with world's third largest population of human immunodeficiency virus /
      acquired immunodeficiency syndrome, offers scope to study such association.
      Objective: Current study (2010-2015) was designed to evaluate if killer
      immunoglobulin-like receptors gene polymorphisms are associated with HIV
      infection outcomes specifically, with long term non progressors. Methods: Killer
      immunoglobulin-like receptors genotyping was done using polymerase chain reaction
      - sequence-specific primer method. Viral load was measured by Cobas Taqman HIV-1
      test. Estimation of CD4 counts was done using BD FACS CD4 count reagent. Results:
      The activating gene frequencies identified were 3DS1 (53.8%), 2DS3 (69.2%), 2DS4
      (76.9%), 2DS5 (69.2%), 2DS1 (76.9%) and 2DS2 (92.3%). The inhibitory gene
      frequencies were 2DL2 (92.3%), 2DL5 (76.9%), 2DL3 (69.5%), 3DL1 (84.6%), 3DL2
      (92.3%) and 2DL1 (100%). The results highlight high frequency of 3DS1/3DL1
      heterozygote and killer immunoglobulin-like receptor 2DS1, among these long term
      non progressors indicating their possible association with slow progression.
      Genotype analysis shows total 13 genotypes, of which 8 genotypes were identified
      for the first time from India. Two genotypes were unique/novel, which were
      unreported. All genotypes observed in this study were considered to be Bx
      genotype (100 %). Limitations: A small sample size (n=13, due to a rare cohort)
      and the absence of control group were the limitations of this study. Conclusions:
      The present study highlights the distribution of killer immunoglobulin-like
      receptor genes in a very rare group of human immunodeficiency virus -1 infected
      individuals - long term non progressors. All the long term non progressors tested
      show the presence of Bx haplotype and each long term non progressors has a
      different killer immunoglobulin-like receptor genotype.

PMID- 29327702
TI  - Laser-assisted surgery and bioscaffold for the treatment of rhinophyma.

PMID- 29327703
TI  - Flexural scaly papules and plaques.

PMID- 29327705
TI  - Diabetes: Towards a coxsackievirus B-based vaccine to combat T1DM.

PMID- 29327707
TI  - Appendiceal goblet cell carcinoids and adenocarcinomas ex-goblet cell carcinoid
      are genetically distinct from primary colorectal-type adenocarcinoma of the
      appendix.
AB  - The appendix gives rise to goblet cell carcinoids, which represent special
      carcinomas with distinct biological and histological features. Their genetic
      background and molecular relationship to colorectal adenocarcinoma is largely
      unknown. We therefore performed a next-generation sequencing analysis of 25
      appendiceal carcinomas including 11 goblet cell carcinoids, 7 adenocarcinomas ex
      goblet cell carcinoid, and 7 primary colorectal-type adenocarcinomas, using a
      modified Colorectal Cancer specific Panel comprising 32 genes linked to
      colorectal and neuroendocrine tumorigenesis. The mutational profiles of these
      neoplasms were compared with those of conventional adenocarcinomas, mixed
      adenoneuroendocrine carcinomas, and neuroendocrine carcinomas of the colorectum.
      In addition, a large-scale pan-cancer sequencing panel covering 409 genes was
      applied to selected cases of goblet cell carcinoid/adenocarcinoma ex-goblet cell
      carcinoid (n=2, respectively). Mutations in colorectal cancer-related genes (eg,
      TP53, KRAS, APC) were rare to absent in both, goblet cell carcinoids and
      adenocarcinomas ex-goblet cell carcinoid, but frequent in primary colorectal-type
      adenocarcinomas of the appendix. Additional large-scale sequencing of selected
      goblet cell carcinoids and adenocarcinomas ex-goblet cell carcinoid revealed
      mutations in Wnt-signaling-associated genes (USP9X, NOTCH1, CTNNA1, CTNNB1,
      TRRAP). These data suggest that appendiceal goblet cell carcinoids and
      adenocarcinomas ex-goblet cell carcinoid constitute a morphomolecular entity,
      histologically and genetically distinct from appendiceal colorectal-type
      adenocarcinomas and its colorectal counterparts. Altered Wnt-signaling associated
      genes, apart from APC, may act as potential drivers of these neoplasms. The
      absence of KRAS/NRAS mutations might render some of these tumors eligible for
      anti-EGFR directed therapy regimens.

PMID- 29327704
TI  - Emerging nonmetabolic functions of skin fat.
AB  - Although the major white adipose depots evolved primarily to store energy,
      secrete hormones and thermo-insulate the body, multiple secondary depots
      developed additional specialized and unconventional functions. Unlike any other
      fat tissue, dermal white adipose tissue (dWAT) evolved a large repertoire of
      novel features that are central to skin physiology, which we discuss in this
      Review. dWAT exists in close proximity to hair follicles, the principal
      appendages of the skin that periodically grow new hairs. Responding to multiple
      hair-derived signals, dWAT becomes closely connected to cycling hair follicles
      and periodically cycles itself. At the onset of new hair growth, hair follicles
      secrete activators of adipogenesis, while at the end of hair growth, a reduction
      in the secretion of activators or potentially, an increase in the secretion of
      inhibitors of adipogenesis, results in fat lipolysis. Hair-driven cycles of dWAT
      remodelling are uncoupled from size changes in other adipose depots that are
      controlled instead by systemic metabolic demands. Rich in growth factors, dWAT
      reciprocally signals to hair follicles, altering the activation state of their
      stem cells and modulating the pace of hair regrowth. dWAT cells also facilitate
      skin repair following injury and infection. In response to wounding, adipose
      progenitors secrete repair-inducing activators, while bacteria-sensing adipocytes
      produce antimicrobial peptides, thus aiding innate immune responses in the skin.

PMID- 29327708
TI  - Myeloproliferative neoplasms with concurrent BCR-ABL1 translocation and JAK2
      V617F mutation: a multi-institutional study from the bone marrow pathology group.
AB  - Myeloproliferative neoplasms arise from hematopoietic stem cells with somatically
      altered tyrosine kinase signaling. Classification of myeloproliferative neoplasms
      is based on hematologic, histopathologic and molecular characteristics including
      the presence of the BCR-ABL1 and JAK2 V617F. Although thought to be mutually
      exclusive, a number of cases with co-occurring BCR-ABL1 and JAK2 V617F have been
      identified. To characterize the clinicopathologic features of myeloproliferative
      neoplasms with concomitant BCR-ABL1 and JAK2 V617F, and define the frequency of
      co-occurrence, we conducted a retrospective multi-institutional study. Cases were
      identified using a search of electronic databases over a decade at six major
      institutions. Of 1570 patients who were tested for both BCR-ABL1 and JAK2 V617F,
      six were positive for both. An additional five patients were identified via
      clinical records providing a total of 11 cases for detailed evaluation. For each
      case, clinical variables, hematologic and genetic data, and bone marrow
      histomorphologic features were analyzed. The sequence of identification of the
      genetic abnormalities varied: five patients were initially diagnosed with a JAK2
      V617F+ myeloproliferative neoplasm, one patient initially had BCR-ABL1+ chronic
      myeloid leukemia, while both alterations were identified simultaneously in five
      patients. Classification of the BCR-ABL1-negative myeloproliferative neoplasms
      varied, and in some cases, features only became apparent following tyrosine
      kinase inhibitor therapy. Seven of the 11 patients showed myelofibrosis, in some
      cases before identification of the second genetic alteration. Our data,
      reflecting the largest reported study comprehensively detailing clinicopathologic
      features and response to therapy, show that the co-occurrence of BCR-ABL1 and
      JAK2 V617F is rare, with an estimated frequency of 0.4%, and most often reflects
      two distinct ('composite') myeloproliferative neoplasms. Although uncommon, it is
      important to be aware of this potentially confounding genetic combination, lest
      these features be misinterpreted to reflect resistance to therapy or disease
      progression, considerations that could lead to inappropriate management.

PMID- 29327706
TI  - Nuclear grade and necrosis predict prognosis in malignant epithelioid pleural
      mesothelioma: a multi-institutional study.
AB  - A recently described nuclear grading system predicted survival in patients with
      epithelioid malignant pleural mesothelioma. The current study was undertaken to
      validate the grading system and to identify additional prognostic factors. We
      analyzed cases of epithelioid malignant pleural mesothelioma from 17 institutions
      across the globe from 1998 to 2014. Nuclear grade was computed combining nuclear
      atypia and mitotic count into a grade of I-III using the published system.
      Nuclear grade was assessed by one pathologist for three institutions, the
      remaining were scored independently. The presence or absence of necrosis and
      predominant growth pattern were also evaluated. Two additional scoring systems
      were evaluated, one combining nuclear grade and necrosis and the other mitotic
      count and necrosis. Median overall survival was the primary endpoint. A total of
      776 cases were identified including 301 (39%) nuclear grade I tumors, 354 (45%)
      grade II tumors and 121 (16%) grade III tumors. The overall survival was 16
      months, and correlated independently with age (P=0.006), sex (0.015), necrosis
      (0.030), mitotic count (0.001), nuclear atypia (0.009), nuclear grade (<0.0001),
      and mitosis and necrosis score (<0.0001). The addition of necrosis to nuclear
      grade further stratified overall survival, allowing classification of epithelioid
      malignant pleural mesothelioma into four distinct prognostic groups: nuclear
      grade I tumors without necrosis (29 months), nuclear grade I tumors with necrosis
      and grade II tumors without necrosis (16 months), nuclear grade II tumors with
      necrosis (10 months) and nuclear grade III tumors (8 months). The mitosis
      necrosis score stratified patients by survival, but not as well as the
      combination of necrosis and nuclear grade. This study confirms that nuclear grade
      predicts survival in epithelioid malignant pleural mesothelioma, identifies
      necrosis as factor that further stratifies overall survival, and validates the
      grading system across multiple institutions and among both biopsy and resection
      specimens. An alternative scoring system, the mitosis-necrosis score is also
      proposed.

PMID- 29327709
TI  - INSM1 expression and its diagnostic significance in extraskeletal myxoid
      chondrosarcoma.
AB  - Extraskeletal myxoid chondrosarcoma is a rare subtype of sarcoma that affects the
      soft tissue and bones in middle-aged and elderly adults. Its diagnosis can be
      challenging, with the differential diagnoses including a wide variety of
      mesenchymal tumors. The line of differentiation of extraskeletal myxoid
      chondrosarcoma has been controversial, but recent evidence suggests a
      neuroendocrine phenotype. INSM1 is a zinc-finger transcription factor that plays
      a pivotal role in neuroendocrine differentiation, and has been proposed as a
      promising immunohistochemical marker of neuroendocrine carcinoma. The aim of this
      study was to determine the prevalence of INSM1 expression in extraskeletal myxoid
      chondrosarcoma and to understand its significance in sarcoma diagnosis. We
      immunostained the representative sections of 31 NR4A3-rearranged extraskeletal
      myxoid chondrosarcomas and 187 histological mimics. Nuclear staining of moderate
      or higher intensity in at least 5% of tumor cells was considered positive. Twenty
      eight of the 31 extraskeletal myxoid chondrosarcomas (90%) were positive for
      INSM1, providing strong evidence for neuroendocrine differentiation. The staining
      was diffuse (>50%) in 17 cases, with most immunopositive tumors showing at least
      focal strong expression. The INSM1 staining extent was not correlated with
      cytomorphology, synaptophysin expression, or fusion types (EWSR1 vs non-EWSR1).
      In contrast, INSM1 expression was negative in 94% of the 187 other mesenchymal
      tumors. INSM1-positive mimics comprised a small subset of chordoma (1 of 10),
      soft tissue myoepithelioma (1 of 20), ossifying fibromyxoid tumor (3 of 10), and
      Ewing sarcoma (3 of 10), among other tumor types. The majority of these cases
      showed labeling in <25% of the tumor cells. Although not entirely sensitive or
      specific, INSM1 could be a potential marker for the diagnosis of extraskeletal
      myxoid chondrosarcoma when molecular genetic access is limited.

PMID- 29327710
TI  - Genome profiling is an efficient tool to avoid the STUMP classification of
      uterine smooth muscle lesions: a comprehensive array-genomic hybridization
      analysis of 77 tumors.
AB  - The diagnosis of a uterine smooth muscle lesion is, in the majority of cases,
      straightforward. However, in a small number of cases, the morphological criteria
      used in such lesions cannot differentiate with certainty a benign from a
      malignant lesion and a diagnosis of smooth muscle tumor with uncertain malignant
      potential (STUMP) is made. Uterine leiomyosarcomas are often easy to diagnose but
      it is difficult or even impossible to identify a prognostic factor at the moment
      of the diagnosis with the exception of the stage. We hypothesize, for uterine
      smooth muscle lesions, that there is a gradient of genomic complexity that
      correlates to outcome. We first tested this hypothesis on STUMP lesions in a
      previous study and demonstrated that this 'gray category' could be split
      according to genomic index into two groups. A benign group, with a low to
      moderate alteration rate without recurrence and a malignant group, with a highly
      rearranged profile akin to uterine leiomyosarcomas. Here, we analyzed a large
      series of 77 uterine smooth muscle lesions (from 76 patients) morphologically
      classified as 19 leiomyomas, 14 STUMP and 44 leiomyosarcomas with
      clinicopathological and genomic correlations. We confirmed that genomic index
      with a cut-off=10 is a predictor of recurrence (P<0.0001) and with a cut-off=35
      is a marker for poor overall survival (P=0.035). For the tumors confined to the
      uterus, stage as a prognostic factor was not useful in survival prediction. At
      stage I, among the tumors reclassified as molecular leiomyosarcomas (ie, genomic
      index >=10), the poor prognostic markers were: 5p gain (overall survival
      P=0.0008), genomic index at cut-off=35 (overall survival P=0.0193), 13p loss
      including RB1 (overall survival P=0.0096) and 17p gain including MYOCD gain
      (overall survival P=0.0425). Based on these findings (and the feasibility of
      genomic profiling by array-comparative genomic hybridization), genomic index, 5p
      and 17p gains prognostic value could be evaluated in future prospective
      chemotherapy trials.

PMID- 29327711
TI  - CD3-positive plasmablastic B-cell neoplasms: a diagnostic pitfall.
AB  - Rare B-cell neoplasms with plasmablastic differentiation may aberrantly express
      CD3 by immunohistochemical staining, which places a great challenge for
      diagnosis. We here studied 17 cases of CD3+ plasmablastic B-cell neoplasms,
      including 12 plasmablastic lymphomas and 5 plasmablastic plasma cell myelomas.
      All 17 cases occurred in the extranodal sites with a male predominance (13/17).
      Four cases were initially misinterpreted by outside institutions, among which
      three were diagnosed as 'peripheral T-cell lymphoma, not otherwise specified' and
      one was classified as 'poorly differentiated neuroendocrine carcinoma'. The
      plasmablastic cells were present in all 17 cases diffusely or in a subset of
      tumor cells. CD3 expression was mostly diffuse (12/17) and moderate to strong
      (11/16) with a cytoplasmic staining pattern (14/16). Other T-cell markers were
      nearly absent, including CD2 (0/10), CD4 (1/13), CD5 (0/14), CD7 (0/11), and CD8
      (0/13). CD138 was positive in all 17 cases and CD79a was variably positive in 8
      of 14 cases. Only one case had immunoreactivity to CD20 (1/17) and PAX5 (1/12).
      CD56 expression and EBV infection were detected in 8/15 and 6/17, respectively.
      No HHV8 infection was noted in all 11 cases tested. Most cases (11/13) revealed
      either kappa or lambda light chain restriction. Of the nine cases studied, six
      had clonal IGH rearrangements but no clonal TRG rearrangements. Our study further
      emphasizes that the accurate classification of CD3+ plasmablastic neoplasms
      requires thorough morphologic examination, incorporation of more B-cell and T
      cell markers in addition to CD3 and CD20, frequent addition of CD138 staining,
      and utilization of necessary molecular and genetic studies.

PMID- 29327712
TI  - Glypican-1 immunohistochemistry is a novel marker to differentiate epithelioid
      mesothelioma from lung adenocarcinoma.
AB  - Histological morphology alone is not sufficient for the pathological diagnosis of
      malignant mesothelioma. Positive and negative immunohistochemical markers are
      necessary to differentiate it from lung adenocarcinoma. As calretinin and D2-40,
      the recognized positive markers of mesothelioma, are expressed in lung
      adenocarcinoma to some extent, novel markers with high specificity are desirable.
      In this study, we investigated the applicability of glypican-1
      immunohistochemistry to differentiate epithelioid mesothelioma from lung
      adenocarcinoma. We investigated 82 cases of epithelioid mesothelioma and 97 cases
      of lung adenocarcinoma for glypican-1 expression by immunohistochemistry using a
      commercially available antibody. All 82 cases of epithelioid mesothelioma showed
      glypican-1 expression, most with diffuse and strong reactivity. In contrast, only
      three cases of lung adenocarcinoma showed focal glypican-1 expression. Glypican-1
      expression showed 100 sensitivity, 97% specificity, and a 98% accuracy rate to
      differentiate epithelioid mesothelioma from lung adenocarcinoma. The sensitivity
      of glypican -1 immunohistochemistry is as high as that of calretinin and D2-40,
      and its specificity is far better than that of calretinin and D2-40. Therefore,
      we recommend including glypican -1 immunohistochemistry as a positive marker of
      epithelioid mesothelioma.

PMID- 29327713
TI  - Expression of enhancer of zeste homolog 2 (EZH2) protein in histiocytic and
      dendritic cell neoplasms with evidence for p-ERK1/2-related, but not MYC- or p
      STAT3-related cell signaling.
AB  - EZH2 is an important enzymatic subunit of the epigenetic regulator polycomb
      repressive complex 2 (PRC2), which controls gene silencing through post
      translational modification, and is overexpressed in various carcinomas and
      hematopoietic neoplasms. We found that the majority of cases of histiocytic and
      dendritic cell neoplasms, including histiocytic sarcoma, follicular dendritic
      cell sarcoma, Langerhans cell histiocytosis, and interdigitating dendritic cell
      sarcoma, show strong EZH2 expression by immunohistochemical staining, in contrast
      to benign histiocytic lesions and normal cellular counterparts, which did not
      show EZH2 expression, suggesting that this molecule may function as an oncogenic
      protein in these neoplasms. We correlated EZH2 expression with that of p-ERK1/2,
      MYC, and p-STAT3, potential regulators of EZH2, and found that 60-80% of these
      cases showed strong p-ERK1/2 expression, and only a minority of cases showed
      positivity for MYC or p-STAT3 in neoplastic cells. In cases of follicular
      dendritic cell sarcoma, Langerhans cell histiocytosis, histiocytic sarcoma, and
      interdigitating dendritic cell sarcoma with strong EZH2 expression, 90%, 89%,
      70%, and 100% of cases showed co-expression of p-ERK1/2 with EZH2, respectively,
      while only a small percentage of these cases showed MYC or p-STAT3 co-expression
      with EZH2 (<=30%). These findings suggest that the p-ERK1/2 signaling cascade,
      but not the p-STAT3 and MYC signaling cascades, may regulate EZH2 expression in
      histiocytic and dendritic cell neoplasms, and that EZH2 and the p-ERK1/2
      signaling cascade could serve as therapeutic targets for the treatment of these
      neoplasms. Interestingly, only a minority of cases of blastic plasmacytoid
      dendritic cell neoplasm exhibited high EZH2 expression, and only a minority of
      these cases showed p-ERK1/2 co-expression, suggesting that alternative mechanisms
      may contribute to tumorigenesis in this aggressive neoplasm.

PMID- 29327714
TI  - A comprehensive flow-cytometry-based immunophenotypic characterization of Burkitt
      like lymphoma with 11q aberration.
AB  - We previously described a subset of MYC translocation-negative aggressive B-cell
      lymphomas resembling Burkitt lymphoma, characterized by proximal gains and distal
      losses in chromosome 11. In the 2016 WHO classification, these MYC-negative
      lymphomas were recognized as a new provisional entity, 'Burkitt-like lymphoma
      with 11q aberration'. Here we present an immunophenotype analysis of Burkitt-like
      lymphomas with 11q aberration. Cells were acquired by fine needle aspiration
      biopsy from 10 young adult patients, 80% of whom presented recurrence-free 5-year
      survival. Twenty-three MYC-positive Burkitt lymphomas, including three carrying
      both MYC rearrangement and 11q aberration, served as controls. By
      immunohistochemistry, all Burkitt-like lymphomas with 11q aberration were
      CD20+/CD10+/BCL6+/BCL2-/MUM1-/MYC+/EBV-, usually LMO2+/CD44-/CD43- and sometimes
      CD56+, and showed high proliferation rate. By flow cytometry, Burkitt-like
      lymphoma with 11q aberration immunophenotypically resembled MYC-positive Burkitt
      lymphoma, except for significantly (adjusted P<0.001) more frequent CD38higher
      expression in Burkitt lymphoma (91% MYC-positive Burkitt lymphoma vs 10% Burkitt
      like lymphoma with 11q aberration), more frequently diminished CD45 expression in
      Burkitt lymphoma (74% vs 10%), an exclusive CD16/CD56 and highly restricted CD8
      expression in Burkitt-like lymphoma with 11q aberration (60% vs 0% and 40% vs 4%,
      respectively). We showed high diagnostic accuracy and effectiveness of flow
      cytometry in Burkitt lymphoma. CD16/CD56 expression without CD38higher and the
      lack of CD16/CD56 with CD38higher expression proves to be a reliable, fast, and
      cost-effective method for diagnosing 11q aberration and MYC rearrangements in
      CD10(+) aggressive lymphomas, respectively. In addition, we confirmed a pattern
      of an inverted duplication with telomeric loss of 11q, as a recurrent 11q
      abnormality, but one case presented alternative changes, possibly resulting in an
      equivalent molecular effect. Our findings reveal similarities along with subtle
      but essential differences in the immunophenotype of Burkitt-like lymphoma with
      11q aberration and MYC-positive Burkitt lymphoma, important for the differential
      diagnosis, but also for understanding the pathogenesis of Burkitt-like lymphoma
      with 11q aberration.

PMID- 29327715
TI  - De novo pure erythroid leukemia: refining the clinicopathologic and cytogenetic
      characteristics of a rare entity.
AB  - Per the revised fourth edition World Health Organization classification of acute
      myeloid leukemia, pure erythroid leukemia is now the sole type of acute erythroid
      leukemia. The diagnosis of this rare entity is often challenging and the
      cytologic overlap with non-neoplastic (eg, megaloblastic anemia) and neoplastic
      entities (eg, other types of acute leukemia and non-hematopoietic malignancies)
      warrants a significant degree of clinical, laboratory, immunophenotypic, and
      genetic investigation. Given the limited number of reports of this rare and
      diagnostically challenging entity, we report detailed clinicopathologic
      characteristics from 15 patients, the largest series thus far, of primary de novo
      pure erythroid leukemia to provide further diagnostic insights into this entity
      and reveal strategies for making the diagnosis. We found that de novo pure
      erythroid leukemia is a disease of adults (median age 68 years), exhibits a
      striking male predominance, is universally associated with an abnormal karyotype
      and has an exceedingly poor overall median survival of 1.4 months. Given the
      general inability of immunophenotypic markers to discriminate neoplastic from non
      neoplastic erythroid proliferations, key features identified in this study to
      help establish the diagnosis of pure erythroid leukemia and exclude mimickers
      include circulating pronormoblasts, clear-cut dysplasia in erythroid,
      granulocytic, and/or megakaryocytic lineage, utilization of a broad
      immunophenotypic panel, TP53 immunohistochemical positivity, and identification
      of a complex, often highly complex, karyotype. Given the gravity of a diagnosis
      of de novo pure erythroid leukemia, it should be rendered with utmost confidence.

PMID- 29327716
TI  - Genomic heterogeneity of ALK fusion breakpoints in non-small-cell lung cancer.
AB  - In lung adenocarcinoma, canonical EML4-ALK inversion results in a fusion protein
      with a constitutively active ALK kinase domain. Evidence of ALK rearrangement
      occurs in a minority (2-7%) of lung adenocarcinoma, and only ~60% of these
      patients will respond to targeted ALK inhibition by drugs such as crizotinib and
      ceritinib. Clinically, targeted anti-ALK therapy is often initiated based on
      evidence of an ALK genomic rearrangement detected by fluorescence in situ
      hybridization (FISH) of interphase cells in formalin-fixed, paraffin-embedded
      tissue sections. At the genomic level, however, ALK rearrangements are
      heterogeneous, with multiple potential breakpoints in EML4, and alternate fusion
      partners. Using next-generation sequencing of DNA and RNA together with ALK
      immunohistochemistry, we comprehensively characterized genomic breakpoints in 33
      FISH-positive lung adenocarcinomas. Of these 33 cases, 29 (88%) had detectable
      DNA level ALK rearrangements involving EML4, KIF5B, or non-canonical partners
      including ASXL2, ATP6V1B1, PRKAR1A, and SPDYA. A subset of 12 cases had material
      available for RNA-Seq. Of these, eight of eight (100%) cases with DNA
      rearrangements showed ALK fusion transcripts from RNA-Seq; three of four cases
      (75%) without detectable DNA rearrangements were similarly negative by RNA-Seq,
      and one case was positive by RNA-Seq but negative by DNA next-generation
      sequencing. By immunohistochemistry, 17 of 19 (89%) tested cases were clearly
      positive for ALK protein expression; the remaining cases had no detectable DNA
      level rearrangement or had a non-canonical rearrangement not predicted to form a
      fusion protein. Survival analysis of patients treated with targeted ALK
      inhibitors demonstrates a significant difference in mean survival between
      patients with next-generation sequencing confirmed EML4-ALK rearrangements, and
      those without (20.6 months vs 5.4 months, P<0.01). Together, these data
      demonstrate abundant genomic heterogeneity among ALK-rearranged lung
      adenocarcinoma, which may account for differences in treatment response with
      targeted ALK inhibitors.

PMID- 29327717
TI  - Combined mutation and copy-number variation detection by targeted next-generation
      sequencing in uveal melanoma.
AB  - Uveal melanoma is a highly aggressive cancer of the eye, in which nearly 50% of
      the patients die from metastasis. It is the most common type of primary eye
      cancer in adults. Chromosome and mutation status have been shown to correlate
      with the disease-free survival. Loss of chromosome 3 and inactivating mutations
      in BAP1, which is located on chromosome 3, are strongly associated with 'high
      risk' tumors that metastasize early. Other genes often involved in uveal melanoma
      are SF3B1 and EIF1AX, which are found to be mutated in intermediate- and low-risk
      tumors, respectively. To obtain genetic information of all genes in one test, we
      developed a targeted sequencing method that can detect mutations in uveal
      melanoma genes and chromosomal anomalies in chromosome 1, 3, and 8. With as
      little as 10 ng DNA, we obtained enough coverage on all genes to detect
      mutations, such as substitutions, deletions, and insertions. These results were
      validated with Sanger sequencing in 28 samples. In >90% of the cases, the BAP1
      mutation status corresponded to the BAP1 immunohistochemistry. The results
      obtained in the Ion Torrent single-nucleotide polymorphism assay were confirmed
      with several other techniques, such as fluorescence in situ hybridization,
      multiplex ligation-dependent probe amplification, and Illumina SNP array. By
      validating our assay in 27 formalin-fixed paraffin-embedded and 43 fresh uveal
      melanomas, we show that mutations and chromosome status can reliably be obtained
      using targeted next-generation sequencing. Implementing this technique as a
      diagnostic pathology application for uveal melanoma will allow prediction of the
      patients' metastatic risk and potentially assess eligibility for new therapies.

PMID- 29327718
TI  - Epithelioid fibrous histiocytoma: molecular characterization of ALK fusion
      partners in 23 cases.
AB  - Epithelioid fibrous histiocytoma is a rare and distinctive cutaneous neoplasm.
      Most cases harbor ALK rearrangement and show ALK overexpression, which
      distinguish this neoplasm from conventional cutaneous fibrous histiocytoma and
      variants. SQSTM1 and VCL have previously been shown to partner with ALK in one
      case each of epithelioid fibrous histiocytoma. The purpose of this study was to
      examine a large cohort of epithelioid fibrous histiocytomas by next-generation
      sequencing to characterize the nature and prevalence of ALK fusion partners. A
      retrospective archival review was performed to identify cases of epithelioid
      fibrous histiocytoma (2012-2016). Immunohistochemistry was performed to confirm
      ALK expression. Targeted next-generation sequencing was applied on RNA extracted
      from formalin-fixed paraffin-embedded tissue to identify the fusion partners.
      Twenty-three cases fulfilled inclusion criteria. The mean patient age was 39
      years (range, 8-74), there was no sex predilection, and >75% of cases involved
      the lower extremities. The most common gene fusions were SQSTM1-ALK (N=12; 52%)
      and VCL-ALK (N=7; 30%); the other four cases harbored novel fusion partners
      (DCTN1, ETV6, PPFIBP1, and SPECC1L). The pattern of ALK immunoreactivity was
      usually granular cytoplasmic (N=12; 52%) or granular cytoplasmic and nuclear
      (N=10; 43%); the case containing an ETV6 fusion partner showed nuclear staining
      alone. There was no apparent relationship between tumor morphology and the ALK
      fusion partner. In summary, SQSTM1 and VCL are the most common ALK fusion
      partners in epithelioid fibrous histiocytoma; DCTN1, ETV6, PPFIBP1, and SPECC1L
      represent rare fusion partners. The proteins encoded by these genes play diverse
      roles in scaffolding, cell adhesion, signaling, and transcription (among others)
      without clear commonalities. These findings expand the oncogenic promiscuity of
      many of these ALK fusion genes, which drive neoplasia in tumors of diverse
      lineages with widely varied clinical behavior. This is the first documented
      account of ETV6-ALK and SPECC1L-ALK translocations in neoplasms.

PMID- 29327719
TI  - The histomorphological spectrum of restrictive chronic lung allograft dysfunction
      and implications for prognosis.
AB  - Chronic lung allograft dysfunction continues to be the main contributor to poor
      long-term allograft survival after lung transplantation. The restrictive
      phenotype of chronic lung allograft dysfunction carries a particularly poor
      prognosis. Little is known about the pathogenetic mechanisms involved in
      restrictive chronic lung allograft dysfunction. In this study, we performed
      histomorphological and immunohistochemical analysis of restrictive chronic lung
      allograft dysfunction lungs. Explant lung tissue from 21 restrictive chronic lung
      allograft dysfunction patients was collected and histopathologic patterns of
      rejection, fibrosis and vascular changes were scored after routine histochemical
      stains and additional immunohistochemistry for endothelial markers and C4d. In
      all, 75% of cases showed evidence of acute cellular rejection; lymphocytic
      bronchiolitis was absent in most lungs, whereas in 55% there was obliterative
      bronchiolitis. Almost half of the cases showed a pattern consistent with
      pleuroparenchymal fibro-elastosis (n=10), and a subset showed nonspecific
      interstitial pneumonia (n=5) or irregular emphysema (n=5). Fibrinous alveolar
      exudates were frequently seen in association with fibrosis (n=6), but no diffuse
      alveolar damage was found. Evidence of microvascular damage was present in most
      cases. An emphysematous pattern of fibrosis was associated with a better survival
      (P=0.0030), whereas fibrinous exudates were associated with a worse survival
      (P=0.0007). In addition to the previously described nonspecific interstitial
      pneumonia and pleuroparenchymal fibro-elastosis patterns in restrictive chronic
      lung allograft dysfunction, we are the first to describe a pattern of fibrosis
      induced subpleural/paraseptal emphysema. This pattern confers a better survival,
      whereas fibrinous exudates are associated with a worse survival. We believe that
      our findings offer a pathogenetic theory for pleuroparenchymal fibro-elastosis in
      restrictive chronic lung allograft dysfunction, and show that restrictive chronic
      lung allograft dysfunction is an increasingly heterogeneous disease with
      presumably different mechanisms of subpattern formation.

PMID- 29327720
TI  - A ten year experience of medical emergencies at Birmingham Dental Hospital.

PMID- 29327721
TI  - Midazolam use for dental conscious sedation: how safe are we?

PMID- 29327722
TI  - Healthy lifestyle habits benefit remission of recurrent aphthous stomatitis and
      RAS type ulceration.
AB  - In a clinical setting, it is not practical to separate recurrent aphthous
      stomatitis (RAS) from RAS-type ulceration in every case, so both conditions have
      been considered together for the purpose of this article. Due to the lack of
      consistently effective therapeutic options for RAS, other approaches to treat the
      disease are considered here, beginning with an analysis of possible aetiological
      factors. The aetiology of RAS, the most common mucosal disease, remains undefined
      thus far. A few researchers have proposed psychological disorders as a major
      factor impacting RAS. Some systemic diseases and lifestyle habits are also
      reported to be associated with RAS; these also impact mental health. I believe
      that all habits contributing to mental health might also benefit patients with
      RAS. I suggest that practitioners of oral medicine should recommend a healthy
      lifestyle to patients with RAS, before prescribing medicines.

PMID- 29327723
TI  - The role of the consultant in restorative dentistry.
AB  - The role of a hospital consultant has changed extensively over the past decade as
      the National Health Service has progressed through a series of challenges
      including an ageing population and rising costs of clinical care. The traditional
      concept of a consultant has changed with different and increased expectations of
      the role as the pressures to deliver high quality patient care, education and
      advice continue to rise in a difficult financial climate. In addition,
      consultants in restorative dentistry are faced with the challenge of a poor
      general awareness of the scope of their speciality and their role. This paper
      provides an update on how the role of the consultant in restorative dentistry has
      evolved in the last decade and how it differs from that of other dental
      specialists and general dental practice.

PMID- 29327724
TI  - Let's get serious about mentoring.
AB  - The piece discusses the benefit of mentoring and the importance of formal
      training, in addition to valuing the skills a mentor can provide. As an
      understanding of mentoring grows within the dental profession, now is the time to
      ensure those who offer mentoring have the techniques, tools and skills to
      complement their professional/clinical expertise.

PMID- 29327726
TI  - Generation of knock-in cynomolgus monkey via CRISPR/Cas9 editing.

PMID- 29327727
TI  - Generation of a precise Oct4-hrGFP knockin cynomolgus monkey model via
      CRISPR/Cas9-assisted homologous recombination.

PMID- 29327725
TI  - Whole-genome sequencing reveals principles of brain retrotransposition in
      neurodevelopmental disorders.
AB  - Neural progenitor cells undergo somatic retrotransposition events, mainly
      involving L1 elements, which can be potentially deleterious. Here, we analyze the
      whole genomes of 20 brain samples and 80 non-brain samples, and characterized the
      retrotransposition landscape of patients affected by a variety of
      neurodevelopmental disorders including Rett syndrome, tuberous sclerosis, ataxia
      telangiectasia and autism. We report that the number of retrotranspositions in
      brain tissues is higher than that observed in non-brain samples and even higher
      in pathologic vs normal brains. The majority of somatic brain retrotransposons
      integrate into pre-existing repetitive elements, preferentially A/T rich L1
      sequences, resulting in nested insertions. Our findings document the fingerprints
      of encoded endonuclease independent mechanisms in the majority of L1 brain
      insertion events. The insertions are "non-classical" in that they are truncated
      at both ends, integrate in the same orientation as the host element, and their
      target sequences are enriched with a CCATT motif in contrast to the classical
      endonuclease motif of most other retrotranspositions. We show that L1Hs elements
      integrate preferentially into genes associated with neural functions and
      diseases. We propose that pre-existing retrotransposons act as "lightning rods"
      for novel insertions, which may give fine modulation of gene expression while
      safeguarding from deleterious events. Overwhelmingly uncontrolled
      retrotransposition may breach this safeguard mechanism and increase the risk of
      harmful mutagenesis in neurodevelopmental disorders.

PMID- 29327728
TI  - Diverse modes of clonal evolution in HBV-related hepatocellular carcinoma
      revealed by single-cell genome sequencing.
AB  - Hepatocellular carcinoma (HCC) is a cancer of substantial morphologic, genetic
      and phenotypic diversity. Yet we do not understand the relationship between
      intratumor heterogeneity and the associated morphologic/histological
      characteristics of the tumor. Using single-cell whole-genome sequencing to
      profile 96 tumor cells (30-36 each) and 15 normal liver cells (5 each), collected
      from three male patients with HBV-associated HCC, we confirmed that copy number
      variations occur early in hepatocarcinogenesis but thereafter remain relatively
      stable throughout tumor progression. Importantly, we showed that specific HCCs
      can be of monoclonal or polyclonal origins. Tumors with confluent multinodular
      morphology are the typical polyclonal tumors and display the highest intratumor
      heterogeneity. In addition to mutational and copy number profiles, we dissected
      the clonal origins of HCC using HBV-derived foreign genomic markers. In
      monoclonal HCC, all the tumor single cells exhibit the same HBV integrations,
      indicating that HBV integration is an early driver event and remains extremely
      stable during tumor progression. In addition, our results indicated that both
      models of metastasis, late dissemination and early seeding, have a role in HCC
      progression. Notably, early intrahepatic spreading of the initiating clone leads
      to the formation of synchronous multifocal tumors. Meanwhile, we identified a
      potential driver gene ZNF717 in HCC, which exhibits a high frequency of mutation
      at both single-cell and population levels, as a tumor suppressor acting through
      regulating the IL-6/STAT3 pathway. These findings highlight multiple distinct
      tumor evolutionary mechanisms in HCC, which suggests the need for specific
      treatment strategies.

PMID- 29327729
TI  - H5N1 influenza virus-specific miRNA-like small RNA increases cytokine production
      and mouse mortality via targeting poly(rC)-binding protein 2.
AB  - Infection of H5N1 influenza virus causes the highest mortality among all
      influenza viruses. The mechanisms underlying such high viral pathogenicity are
      incompletely understood. Here, we report that the H5N1 influenza virus encodes a
      microRNA-like small RNA, miR-HA-3p, which is processed from a stem loop
      containing viral RNA precursor by Argonaute 2, and plays a role in enhancing
      cytokine production during H5N1 infection. Mechanistic study shows that miR-HA-3p
      targets poly(rC)-binding protein 2 (PCBP2) and suppresses its expression.
      Consistent with PCBP2 being an important negative regulator of RIG-I/MAVS
      mediated antiviral innate immunity, suppression of PCBP2 expression by miR-HA-3p
      promotes cytokine production in human macrophages and mice infected with H5N1
      virus. We conclude that miR-HA-3p is the first identified influenza virus-encoded
      microRNA-like functional RNA fragment and a novel virulence factor contributing
      to H5N1-induced 'cytokine storm' and mortality.

PMID- 29327730
TI  - Eosinophil-derived CCL-6 impairs hematopoietic stem cell homeostasis.
AB  - Eosinophils (Eos) have been long considered as end-stage effector cells in the
      hierarchical hematopoietic system. Numerous lines of evidence have suggested that
      Eos are multifunctional leukocytes with respect to the initiation, propagation
      and regulation of various inflammatory or immune reactions, especially in
      allergic diseases. Recent studies have shown that Eos are also required for
      maintenance of bone marrow plasma cells and differentiation of B cells. However,
      it remains unclear whether Eos contributes to regulation of hematopoietic stem
      cell (HSC) homeostasis. Here, we demonstrate that Eos disrupt HSC homeostasis by
      impairing HSC quiescence and reconstitution ability in wild-type mice following
      ovalbumin (OVA) challenge and even by causing bone marrow HSC failure and
      exhaustion in Cd3delta-Il-5 transgenic mice. The impaired maintenance and
      function of HSCs were associated with Eos-induced redox imbalance (increased
      oxidative phosphorylation and decreased anti-oxidants levels). More importantly,
      using mass spectrometry, we determined that CCL-6 is expressed at a high level
      under eosinophilia. We demonstrate that CCL-6 is Eos-derived and responsible for
      the impaired HSC homeostasis. Interestingly, blockage of CCL-6 with a specific
      neutralizing antibody, restored the reconstitution ability of HSCs while
      exacerbating eosinophilia airway inflammation in OVA-challenged mice. Thus, our
      study reveals an unexpected function of Eos/CCL-6 in HSC homeostasis.

PMID- 29327731
TI  - Transoral robotic surgery in Eagle's syndrome: our experience on four patients.
AB  - Eagle's syndrome is characterised by focal pain in the tonsillar fossa on wide
      mouth opening or head rotation and various accompanying symptoms. While the
      syndrome is difficult to diagnose, shortening the styloid process via a transoral
      or transcervical surgical approach has been shown to be the most effective
      treatment. The aim of this article was to document our experience with a
      transoral robotic approach to treat Eagle's syndrome and to present the outcomes
      of four patients. We reviewed the cases of four patients with Eagle's syndrome
      who underwent transoral robotic surgery (TORS). The average age of patients was
      53.75 years, and there were equal numbers of males and females. The styloid
      processes were reconstructed in 3D from the preoperative CT scans and were
      measured as an average of 4.18 cm (range 3.3-5.1). The mean set-up time and
      operation times were less than 10 minutes and 30 minutes, respectively. All
      patients were completely relieved of symptoms, and were able to restart an oral
      diet on post-operative day 1. No patient suffered intraoperative or postoperative
      complication, including cranial nerve injury, haemorrhage, or deep neck
      infection. In our experience, transoral excision of the styloid process via a
      robotic approach can be considered as a feasible treatment option for Eagle's
      syndrome.

PMID- 29327732
TI  - A miRNA signature suggestive of nodal metastases from laryngeal carcinoma.
AB  - The discovery that miRNAs are frequently deregulated in tumours offers the
      opportunity to identify them as prognostic and diagnostic markers. The aim of
      this multicentric study is to identify a miRNA expression profile specific for
      laryngeal cancer. The secondary endpoint was to identify specific deregulated
      miRNAs with potential as prognostic biomarkers for tumour spread and nodal
      involvement, and specifically to search for a miRNA pattern pathognomonic for N+
      laryngeal cancer and for N- tissues. We identified 20 miRNAs specific for
      laryngeal cancer and a tissue-specific miRNA signature that is predictive of
      lymph node metastases in laryngeal carcinoma characterised by 11 miRNAs, seven of
      which are overexpressed (upregulated) and four downregulated. These results allow
      the identification of a group of potential specific tumour biomarkers for
      laryngeal carcinoma that can be used to improve its diagnosis, particularly in
      early stages, as well as its prognosis.

PMID- 29327733
TI  - Orthopaedic treatment effects of functional therapy on the sagittal pharyngeal
      dimensions in subjects with sleep-disordered breathing and Class II malocclusion.
AB  - The purpose of this cephalometric study was to evaluate the craniofacial changes
      induced by functional treatment of mandibular advancement with special regard to
      pharyngeal sagittal airway dimensions, tongue and hyoid bone position in subjects
      with sleep-disordered breathing (SDB) and dentoskeletal Class II malocclusions
      compared with an untreated Class II control group. 51 subjects (24 female, 27
      male; mean age 9.9 +/- 1.3 years) with Class II malocclusion and SDB
      consecutively treated with a functional appliance (Modify Monobloc, MM) were
      compared with a control group of 31 subjects (15 males, 16 females; mean age 10.1
      +/- 1.1) with untreated Class II malocclusion. For the study group, mode of
      breathing was defined by an otorhinolaryngologist according to complete physical
      examination. The parents of all participants completed a modified version of the
      paediatric sleep questionnaire, PSQ-SRBD Scale, by Ronald Chervin (the Italian
      version in 22 items form) before and after the trial. Lateral cephalograms were
      available at the start and end of treatment with the MM. Descriptive statistics
      were used for all cephalometric measurements in the two groups for active
      treatment changes. Significant, favourable skeletal changes in the mandible were
      observed in the treated group after T2. Significant short-term changes in
      sagittal airway dimensions, hyoid position and tongue position were induced by
      functional therapy of mandibular advancement in subjects with Class II
      malocclusion and SDB compared with untreated controls. After orthodontic
      treatment, a significant reduction in diurnal symptoms was observed in 45 of the
      51 participants who had received an oral appliance. Orthodontic treatment is
      considered to be a potential therapeutic approach for SDB in children.
      Orthodontists are playing an increasingly important role in managing snoring and
      respiratory problems by oral mandibular advancement devices and rapid maxillary
      expansion.

PMID- 29327734
TI  - Clinical study of extrapulmonary head and neck tuberculosis in an urban setting.
AB  - Tuberculosis (TB) of the head and neck region is quite common in endemic
      countries, but is still misdiagnosed due to its varied presentation and different
      sites of involvement. The aims of the present study were to present the
      diversities of presentation of head and neck tuberculosis with the diagnostic
      predicaments faced during evaluation and to assess treatment response to anti
      tubercular treatment (ATT). We analysed 48 patients with head and neck
      tuberculosis who presented to the Department of Otorhinolaryngology in our
      tertiary care urban hospital over a period of two years from 2013 to 2015 and
      recorded their data, which included presenting complaints, local and systemic
      examination findings, investigation results and treatment outcomes. The results
      showed that majority (64.5%) of cases were female and none of the patients were
      HIV positive. The most common manifestation was cervical lymphadenopathy (81.25%)
      with level II being the most commonly affected (31.3%). Three of the 48 patients
      had coexisting pulmonary TB. Fine needle aspiration cytology (FNAC),
      histopathological diagnosis and acid fast bacilli (AFB) staining were used to
      confirm diagnosis. All patients were treated with Category I ATT, which achieved
      cure in 96.8% of cases. Though cervical lymphadenitis is the most common
      presentation of head and neck TB, isolated involvement of the sinonasal region,
      larynx, oral cavity and other sub-sites are not solely unknown entities. It is,
      therefore, important for clinicians to be aware of atypical and misleading
      presentations and consider TB as a major differential diagnosis in the head and
      neck region, even in non-immunocompromised individuals.

PMID- 29327736
TI  - Balloon dilation of the Eustachian tube: clinical experience in the management of
      126 children.
AB  - Balloon dilation of the Eustachian tube has been recently introduced as a novel
      and minimally invasive method for treating chronic obstructive Eustachian tube
      dysfunction. For the first time worldwide, we assessed the role of this technique
      in the treatment of children with Eustachian tube dysfunction who did not respond
      to other treatments. We retrospectively analysed the medical records of 60
      children (mean age: 6.3 years, range: 28 months to 12 years) who underwent
      balloon dilation of the Eustachian tube using the Bielefeld balloon catheter. In
      addition, the parents of a further 66 children who underwent balloon dilation
      (mean age: 8 years, range: 4 to 13 years) were asked to complete a standardised
      written questionnaire and were interviewed by telephone about the postoperative
      course of their children. There were no complications during surgery. Clinical
      symptoms improved in more than 80% of patients. No patient reported a
      deterioration of symptoms. Of the participating parents, 81.3% were very
      satisfied or satisfied with the outcome of treatment. Balloon dilation is a
      rapid, simple and safe method for the treatment of both adults and children with
      Eustachian tube dysfunction that does not respond to other treatments. Further
      studies, ideally multicentre studies, are required in order to optimise the
      definition of existing and potential new indications for this treatment approach
      and to establish this treatment in the management of children with refractory
      chronic Eustachian tube dysfunction.

PMID- 29327735
TI  - Acquired sensorineural hearing loss in children: current research and therapeutic
      perspectives.
AB  - The knowledge of mechanisms responsible for acquired sensorineural hearing loss
      in children, such as viral and bacterial infections, noise exposure,
      aminoglycoside and cisplatin ototoxicity, is increasing and progressively
      changing the clinical management of affected patients. Viral infections are by
      far the most relevant cause of acquired hearing loss, followed by aminoglycoside
      and platinum derivative ototoxicity; moreover, cochlear damage induced by noise
      overexposure, mainly in adolescents, is an emerging topic. Pharmacological
      approaches are still challenging to develop a truly effective cochlear
      protection; however, the use of steroids, antioxidants, antiviral drugs and other
      small molecules is encouraging for clinical practice. Most of evidence on the
      effectiveness of antioxidants is still limited to experimental models, while the
      use of corticosteroids and antiviral drugs has a wide correspondence in
      literature but with controversial safety. Future therapeutic perspectives include
      innovative strategies to transport drugs into the cochlea, such as molecules
      incorporated in nanoparticles that can be delivered to a specific target.
      Innovative approaches also include the gene therapy designed to compensate for
      abnormal genes or to make proteins by introducing genetic material into cells;
      finally, regenerative medicine (including stem cell approaches) may play a
      central role in the upcoming years in hearing preservation and restoration even
      if its role in the inner ear is still debated.

PMID- 29327737
TI  - Uphill/downhill nystagmus.
AB  - Differential diagnosis between peripheral and central spontaneous nystagmus can
      be difficult to classify (as peripheral or central) even on the basis of criteria
      recommended in the recent literature. The aim of this paper is to use the
      combination of spontaneous nystagmus and ocular tilt reaction to determine the
      site of origin of the disease that causes nystagmus. We propose to classify the
      nystagmus in: 1) "Uphill" nystagmus in which the nystagmus takes on an inclined
      plane and the direction of the fast phase is towards the hypertropic eye (this
      type of nystagmus is likely peripheral); 2) "Downhill" nystagmus when the
      nystagmus beats toward the hypotropic eye (this type of nystagmus is likely
      central); 3) "Flat" nystagmus when the plane on which nystagmus beats is
      perfectly horizontal: in this case, we cannot say anything about the site of
      lesion (it was only detected in 15% of cases). The spatial position of nystagmus
      vector has to be considered as an intrinsic characteristic of the nystagmus
      itself (as direction, frequency, angular velocity etc.) and must be reported in
      the description, possibly giving an indication of the site of damage (peripheral
      or central). In particular, similar results are obtained by comparing the
      inclination of the nystagmus with the head impulse test (HIT, considered the best
      bedside test now available). It seems that this sign may confirm HIT for safer
      diagnosis or replace it in case of doubt. In contrast, in case of "Flat"
      nystagmus (probably attributable to the fact that the utricular maculae are
      spared), HIT can replace observation of the plane of the nystagmus. Thus, the two
      signs confirm and integrate each other. The test does not require additional time
      and is not tedious for the patient. It is proposed that it be included in the
      evaluation of spontaneous nystagmus in everyday clinical practice.

PMID- 29327738
TI  - Increased Mortality in Male Recipients of Red Cells from ever Pregnant Female
      Donors: mHAGs on Red Cells to Blame?

PMID- 29327740
TI  - Correction: Neither slim nor fat: estimating the mass of the dodo (Raphus
      cucullatus, Aves, Columbiformes) based on the largest sample of dodo bones to
      date.
AB  - [This corrects the article DOI: 10.7717/peerj.4110.].

PMID- 29327739
TI  - Numerical Simulation of Thrombotic Occlusion in Tortuous Arterioles.
AB  - Tortuous microvessels alter blood flow and stimulate thrombosis but the physical
      mechanisms are poorly understood. Both tortuous microvessels and abnormally large
      platelets are seen in diabetic patients. Thus, the objective of this study was to
      determine the physical effects of arteriole tortuosity and platelet size on the
      microscale processes of thrombotic occlusion in microvessels. A new lattice
      Boltzmann method-based discrete element model was developed to simulate the fluid
      flow field with fluid-platelet coupling, platelet interactions, thrombus
      formation, and thrombotic occlusion in tortuous arterioles. Our results show that
      vessel tortuosity creates high shear stress zones that activate platelets and
      stimulate thrombus formation. The growth rate depends on the level of tortuosity
      and the pressure and flow boundary conditions. Once thrombi began to form,
      platelet collisions with thrombi and subsequent activations were more important
      than tortuosity level. Thrombus growth narrowed the channel and reduced the flow
      rate. Larger platelet size leads to quicker decrease of flow rate due to larger
      thrombi that occluded the arteriole. This study elucidated the important roles
      that tortuosity and platelet size play in thrombus formation and occlusion in
      arterioles.

PMID- 29327741
TI  - Fabrication and assessment of an electrospun polymeric microfiber-based platform
      under bulk flow conditions with rapid and efficient antigen capture.
AB  - This study investigated the fabrication and proof of concept design demonstrating
      rapid and highly sensitive antigen capture utilizing electrospun polystyrene (PS)
      microfiber mat substrates paired with vacuum pump pressurization to induce bulk
      flow. In comparison with conventional flat PS surfaces used for immunoassay
      purposes, this system optimizes the increased surface area of the electrospun
      polystyrene (ESPS) fiber mat substrates and the accelerated propagation of the
      antigen through the detection platform by using a vacuum pump to enable efficient
      and rapid antigen capture. The novelty of this work was demonstrated through a
      parametric study detailing how a fiber substrate can capture antigen sensitively
      and at high speeds. In terms of sensitivity, the current system is comparable to
      the conventionally used flat PS substrates. Additionally, the amount of antigen
      captured on a flat PS substrate in 60 minutes was surpassed in under 5 seconds
      when utilizing the ESPS-vacuum system. Three-dimensional ESPS fiber mats were
      then noted as a comparison between Damkohler numbers and between flat PS and ESPS
      vacuum systems. The bulk flow of the ESPS-vacuum system allows for a Damkohler
      number of 0.37 indicating a balance between the flow rate and the reaction rate
      as opposed to a PS flat platform of 5.80 * 104 which illustrates a diffusion rate
      limited system. Finally, the overall ESPS-vacuum system was tested for its
      immunoassay capability. A sandwich fluorescence-based immunoassay was performed
      on both PS flat-diffusion and ESPS-vacuum systems. The ESPS-vacuum system
      indicated a wider detection range capability from 5 to 1000 ng mL-1 in comparison
      with the PS flat-diffusion system at 5 to 100 ng mL-1.

PMID- 29327742
TI  - Targeting cleanups towards a more sustainable future.
AB  - A tension arises between society's disposition to protect people at risk from
      environmental pollution, and an aversion towards the potential harmful side
      effects associated with cleanup activities. Here we explore how setting different
      cleanup standards may influence some of the environmental, social, and economic
      side-effects of remediation, and how they can be quantified for incorporation
      into cleanup target setting; these include (1) secondary environmental impacts,
      assessed by life cycle assessment (LCA); (2) fatalities and injuries, assessed by
      actuarial risk analysis; and (3) the cost effectiveness of stringent cleanup
      standards, assessed by the incremental cost-effectiveness ratio (ICER). We argue
      that only by using optimal cleanup standards that integrate quantified
      remediation side-effects with health risk assessment (HRA) can the green and
      sustainable remediation (GSR) movement maximize its potential. Together, the
      combined approaches may provide a more holistic management of risks for a more
      sustainable future.

PMID- 29327743
TI  - The unexpected racemization and hydrogen-deuterium exchange of the hydrogen at
      the alpha-carbon of proline analogs containing the 5-azoniaspiro[4.4]nonyl-group.
AB  - Recently, we developed a novel non-fragmenting quaternary ammonium ionization tag
      for the mass spectrometric sensitive sequencing of peptides, based on the N-spiro
      proline residue (5-azoniaspiro[4.4.]nonyl-carbonyl). Herein, we present an
      unexpected racemization and the hydrogen-deuterium exchange (HDX) at the alpha-C
      atom of the proline derivative under basic aqueous conditions (1% water solution
      of triethylamine). The deuterium atom, substituted for the alpha-C atom, does not
      undergo back-exchange under acidic aqueous conditions which makes the deuterated
      isotopologue a promising stabile isotope-coded internal standard for quantitative
      analysis by mass spectrometry. The applicability of the prepared isotopologues of
      the quaternary ammonium salt labeled peptides for quantification experiments
      using the isotopic dilution method was also examined.

PMID- 29327744
TI  - Spinel Co3O4 nanomaterials for efficient and stable large area carbon-based
      printed perovskite solar cells.
AB  - Carbon based perovskite solar cells (PSCs) are fabricated through easily scalable
      screen printing techniques, using abundant and cheap carbon to replace the hole
      transport material (HTM) and the gold electrode further reduces costs, and carbon
      acts as a moisture repellent that helps in maintaining the stability of the
      underlying perovskite active layer. An inorganic interlayer of spinel cobaltite
      oxides (Co3O4) can greatly enhance the carbon based PSC performance by
      suppressing charge recombination and extracting holes efficiently. The main focus
      of this research work is to investigate the effectiveness of Co3O4 spinel oxide
      as the hole transporting interlayer for carbon based perovskite solar cells
      (PSCs). In these types of PSCs, the power conversion efficiency (PCE) is
      restricted by the charge carrier transport and recombination processes at the
      carbon-perovskite interface. The spinel Co3O4 nanoparticles are synthesized using
      the chemical precipitation method, and characterized by X-ray diffraction (XRD),
      X-ray absorption spectroscopy (XAS), field emission scanning electron microscopy
      (FESEM), transmission electron microscopy (TEM) and UV-Vis spectroscopy. A screen
      printed thin layer of p-type inorganic spinel Co3O4 in carbon PSCs provides a
      better-energy level matching, superior efficiency, and stability. Compared to
      standard carbon PSCs (PCE of 11.25%) an improved PCE of 13.27% with long-term
      stability, up to 2500 hours under ambient conditions, is achieved. Finally, the
      fabrication of a monolithic perovskite module is demonstrated, having an active
      area of 70 cm2 and showing a power conversion efficiency of >11% with virtually
      no hysteresis. This indicates that Co3O4 is a promising interlayer for efficient
      and stable large area carbon PSCs.

PMID- 29327745
TI  - Bipyridine-triggered modulation of structure and properties of zinc
      diphosphonates: coordination role vs. template rule.
AB  - Two zinc-diphosphonates driven by 4,4'-bipyridine (4,4'-bipy), [Zn4(HEDP)2(4,4'
      bipy)2].4.5(H2O) (1) and (H2-4,4'-bipy)0.5.[Zn3(HEDP)(H2EDP)(H2O)].1.5(H2O) (2),
      were solvothermally prepared (HEDP = CH3C(OH)(PO3)2, 1
      hydroxyethylidenediphosphonate). Compound 1 features a layered structure with the
      Zn-HEDP chains as supramolecular units and 4,4'-bipy as interchain linkers.
      Compound 2 possesses a Zn-HEDP layer with protonated 4,4'-bipy as template. The
      structure differences between the two compounds are mainly ascribed to the
      distinct role of 4,4'-bipy in the process of in situ assembly. In compound 1, the
      4,4'-bipy moiety acts as coordinative unit to participate in the formation of the
      resulting architecture. However, in compound 2, the protonated 4,4'-bipy serves
      as template to direct the formation of the final structure. The luminescence and
      proton conduction of the two compounds were investigated. Compounds 1 and 2
      exhibit intense blue fluorescence; compound 2 has a proton conductivity of 2.61 *
      10-4 S cm-1 at 100% relative humidity and 70  degrees C.

PMID- 29327747
TI  - Temperature- and excitation wavelength-dependent emission in a manganese(ii)
      complex.
AB  - A mononuclear manganese(ii) complex with a chelating 4-(3,5-diphenyl-1H-pyrazol-1
      yl)-6-(piperidin-1-yl)pyrimidine ligand (L), [MnL2Cl2].H2O, shows intriguing
      excitation wavelength-dependent emission. Depending on the excitation wavelength,
      the complex demonstrates three emission bands with the maxima at 380 nm, 440 nm
      and 495 nm. The 380 nm and 440 nm emissions originate from the pi -> pi* and n ->
      pi* ligand-centered transitions. The long-wave 495 nm emission with microsecond
      lifetimes is related to the d-d transitions and/or metal-to-ligand and halogen-to
      ligand charge transfer. The emission behavior of this complex is strongly
      temperature-dependent: upon cooling from 300 K down to 77 K, the intensity of
      emission considerably increases. The enhancement of the luminescence upon cooling
      is accompanied by the appearance of the vibrational structure. This complex is
      the first example of manganese(ii) complexes demonstrating excitation wavelength
      dependent emission.

PMID- 29327746
TI  - Silk nanoparticles: from inert supports to bioactive natural carriers for drug
      delivery.
AB  - Silk proteins have been studied and employed for the production of drug delivery
      (nano)systems. They show excellent biocompatibility, controllable
      biodegradability and non-immunogenicity and, if needed, their properties can be
      modulated by blending with other polymers. Silk fibroin (SF), which forms the
      inner core of silk, is a (bio)material officially recognized by the Food and Drug
      Administration for human applications. Conversely, the potential of silk sericin
      (SS), which forms the external shell of silk, could still be considered under
      evaluation. At the best of our knowledge, nanoparticles based on silk sericin
      "alone" cannot be produced, due to its physicochemical instability influenced by
      extreme pH, high water solubility and temperature; for these reasons, it almost
      always needs to be combined with other polymers for the development of drug
      delivery systems. In this review, we focused on silk proteins as bioactive
      natural carriers, since they show not only optimal features as inert excipients,
      but also remarkable intrinsic biological activities. SF has anti-inflammatory
      properties, while SS presents antioxidant, anti-tyrosine, anti-aging, anti
      elastase and anti-bacterial features. Here, we give an overview on SF or SS silk
      based nanosystems, with particular attention on the production techniques.

PMID- 29327748
TI  - Four new metal-organic frameworks based on diverse secondary building units:
      sensing and magnetic properties.
AB  - Four new metal-organic frameworks (MOFs), {[Zn3(L)(OH)(H2O)5].NMP.2H2O}n (1),
      {[H2N(Me)2][Zn2(L)(H2O)].DMF.H2O}n (2), {[Co5(L)2(H2O)11].2H2O}n (3) and
      {[Mn5(L)2(H2O)12].6H2O}n (4), were assembled employing a symmetrical V-shaped
      rigid multicarboxylic acid ligand H5L (H5L = 2,4-di(3',5'
      dicarboxylphenyl)benzoic acid) with different metal ions, resulting in versatile
      frameworks as well as various types of coordination modes of H5L. 1 forms a three
      dimensional (3D) 4-connected sra net based on trinuclear [Zn3(MU3-OH)(MU2
      COO)(MU1-COO)4] clusters, while 2 displays a 3D (4,6)-connected net based on two
      types of binuclear [Zn2(MU2-COO)2(MU1-COO)4] and [Zn2(MU2-COO)4] clusters. 3 and
      4 contain similar [M3(MU2-COO)4(MU1-COO)2] (3, M = Co; 4, M = Mn) clusters but
      result in different 4-connected 3D and 2D frameworks, respectively. 1 and 2 show
      solid-state luminescence properties at ambient temperature. Meanwhile, 1 shows
      high selectivity and sensitivity for not only Fe3+ cations but also for CrO42-,
      Cr2O72- and MnO4- anions via a luminescence quenching effect with a low detection
      limit, which thus means that it could be a potential crystalline material for
      detecting these anions. The mechanisms of the quenching effect and sensing
      properties of 1 are discussed in detail. In addition, 3 and 4 have the presence
      of antiferromagnetic interactions between the metal ions.

PMID- 29327749
TI  - Fabrication of high-performance graphene nanoplatelet-based transparent
      electrodes via self-interlayer-exfoliation control.
AB  - Graphene nanoplatelets (GNP) have attracted considerable attention due to their
      high yield and fabrication route that is scalable to enable graphene production.
      However, the absence of a means of fabricating a transparent and conductive GNP
      film has been the biggest obstacle to the replacement of pristine graphene. Here,
      we report on a novel means of fabricating uniform and thin GNP-based high
      performance transparent electrodes for flexible and stretchable optoelectronic
      devices involving the use of an adhesive polymer layer (PMMA) as a GNP layer
      controller and by forming a hybrid GNP/AgNW electrode embedded on PET or PDMS.
      Relative to the commercially available indium tin oxide (ITO) film on a PET
      substrate, a GNP-based electrode composed of hybrid GNP/AgNW on PET exhibits
      superb optical, physical, and electrical properties: a sheet resistance of 12
      Omega sq-1 with 87.4% transmittance, a variable work function from 4.16 to 5.26
      eV, an ultra-smooth surface, a rate of resistance increase of only 4.0% after 100
      000 bending cycles, stretchability to 50% of tensile strain, and robust stability
      against oxidation. Moreover, the GNP-based electrode composed of hybrid Cl-doped
      GNP/AgNW shows outstanding performance in actual organic light-emitting diodes
      (OLEDs) by exhibiting an increased current efficiency of 29.5% and an increased
      luminous efficiency of 36.2%, relative to the commercial ITO electrode on PET.

PMID- 29327750
TI  - Synthesis and reactivity of an anionic allenylidene complex.
AB  - The reaction of [W([triple bond, length as m-dash]CC[triple bond, length as m
      dash]CSiMe3)(CO)2(Tp*)] (Tp* = hydrotris(dimethylpyrazolyl)borate) with MeLi
      generates the first example of an anionic allenylidene complex Li[W([double bond,
      length as m-dash]C[double bond, length as m-dash]C[double bond, length as m
      dash]CMeSiMe3)(CO)2(Tp*)] which reacts with electrophiles (H+, Me+) at the beta
      carbon to afford vinylcarbyne (allylidyne) complexes [W([triple bond, length as m
      dash]CCE[double bond, length as m-dash]CMeSiMe3)(CO)2(Tp*)] (E = H, Me), and with
      bromine provides the unprecedented binuclear bis(carbyne) complex {C([double
      bond, length as m-dash]CMeSiMe3)C[triple bond, length as m-dash]W(CO)2(Tp*)}2via
      oxidative C-C coupling at the beta-carbon.

PMID- 29327751
TI  - A novel covalent post-synthetically modified MOF hybrid as a sensitive and
      selective fluorescent probe for Al3+ detection in aqueous media.
AB  - A modified MOF named UiO-66-NH2-SA was synthesized based on the covalent post
      synthetic attachment of the MOFs (UiO-66-NH2) and salicylaldehyde via a Schiff
      base reaction. The as-prepared functionalized UiO-66-NH2-SA not only maintains
      its structural integrity during the PSM process, but also shows excellent
      luminescence and good fluorescence stability in water. It was further utilized as
      a novel fluorescent probe for detecting of Al3+. The fluorescence intensity of
      UiO-66-NH2-SA increased linearly upon increasing the concentration of Al3+ in the
      range of 0-500 MUM with a detection limit of 6.98 MUM. The possible mechanism is
      discussed. This study presents a new ratiometric and colorimetric Al3+
      fluorescent sensor. The good fluorescence stability of UiO-66-NH2-SA in aqueous
      media, the low detection limit and the broad linear in sensing Al3+ indicate its
      high potential in practical applications.

PMID- 29327752
TI  - Chiral evolution of carbon dots and the tuning of laccase activity.
AB  - Chirality has attracted extensive attention in many fields ranging from chemistry
      to life sciences. Carbon dots (CDs) with good biocompatibility and unique
      photochemical properties have become a new star in the nanocarbon family. Endowed
      with chirality, CDs will exhibit more marvellous properties and bridge the fields
      of material chemistry and life sciences tightly. Herein, we report a facile one
      step alkali-assisted electrochemical method to fabricate chiral CDs from cysteine
      (cys). We showed the chiral evolution of CDs with highly symmetrical circular
      dichroism (CD) signals in the range from 205 to 350 nm. These chiral CDs have
      been further demonstrated to be capable of tuning the activity of laccase: the l
      CDs can improve the activity of the enzyme up to 20.2%, whereas the d-CDs
      decrease the activity to 10.4%. A series of experiments confirm that it is the
      synergistic effect of nanosize and chirality of CDs that induces the change in
      the structure of laccase and thus leads to the tuning of the laccase activity.

PMID- 29327753
TI  - Recyclable (Fe3O4-NaYF4:Yb,Tm)@TiO2 nanocomposites with near-infrared enhanced
      photocatalytic activity.
AB  - Herein, the design and synthesis of a multifunctional (Fe3O4-NaYF4:Yb,Tm)@TiO2
      photocatalyst through a facile sol-gel process combined with electrostatic self
      assembly has been reported. Particularly, as an upconversion sensor, NaYF4:Yb,Tm
      nanoparticles have the ability to convert near-infrared (NIR) light into
      ultraviolet (UV) emissions, so that the catalytic body TiO2 can indirectly
      utilize the NIR part of sunlight but not UV light. The excellent photocatalytic
      activity of the hybrid samples is evaluated using a model of the degradation of
      methylene blue (MB). Most importantly, the obtained materials exhibit remarkable
      magnetic properties because of the addition of a magnetic component (Fe3O4),
      therefore, the photocatalysts possess desired recyclability and reusability,
      which is significant for actual applications. Finally, the possible
      photocatalysis mechanism of the nanohybrids is discussed and hydroxyl radicals
      (OH) are confirmed as the main reactive species.

PMID- 29327754
TI  - Affinity resins as new tools for identifying target proteins of ascorbic acid.
AB  - l-Ascorbic acid (AA) has diverse physiological functions, but little is known
      about the functional mechanisms of AA. In this study, we synthesized two types of
      affinity resin on which AA is immobilized in a stable form to identify new AA
      targeted proteins, which can provide important clues for elucidating unknown
      functional mechanisms of AA. To our knowledge, an affinity resin on which AA as a
      ligand is immobilized has not been prepared, because AA is very unstable and
      rapidly degraded in an aqueous solution. By using the affinity resins, cytochrome
      c (cyt c) was identified as an AA-targeted protein, and we showed that oxidized
      cyt c exhibits specific affinity for AA. These results suggest that two kinds of
      AA-affinity resin can be powerful tools to identify new target proteins of AA.

PMID- 29327755
TI  - Reversible three equal-step spin crossover in an iron(ii) Hofmann-type metal
      organic framework.
AB  - A novel bent ligand-pillared three-dimensional Hofmann-type metal-organic
      framework, [FeII(Hbpt)Pt(CN)4].1/2Hbpt.1/2CH3OH.5/2H2O [1, Hbpt = 4,4'-(1H-1,2,4
      triazole-3,5-diyl) dipyridine], was synthesized and crystallographically and
      magnetically characterized, which showed incomplete three-step spin-crossover
      behavior with a reversible three equal-step sequence of HS1.00 <-> HS0.75LS0.25 <
      > HS0.5LS0.5 <-> HS0.25LS0.75.

PMID- 29327757
TI  - Rapid and sensitive detection of neuron specific enolase with a polydopamine
      coated plasmonic chip utilizing a rear-side coupling method.
AB  - A rapid and sensitive detection of a cancer marker, neuron specific enolase
      (NSE), is demonstrated by using a disposable silver plasmonic chip functionalized
      with a mussel-inspired polydopamine (PDA) coating. A plasmonic chip consisting of
      a diffraction grating coated with a silver thin film is used for the excitation
      of propagating surface plasmon resonance through a rear-side grating coupling
      method. Simple and quick bio-functionalization of the sensor surface is performed
      by PDA coating which requires 20 min for deposition, and allows direct attachment
      of the capture antibody without using any coupling agents. A fluorescence based
      sandwich immunoassay is used for the detection of NSE by utilizing surface
      plasmon enhanced fluorescence (SPF) spectroscopy. The developed biosensor scheme
      provides approximately linear sensor responses for the sample containing NSE with
      the concentration around the clinically important value (12 ng mL-1) in both
      buffer and diluted human serum (25 vol% to a buffer solution). The detection
      limit for NSE is 0.5 ng mL-1 (11 pM) and 1.4 ng mL-1 (30 pM) in a buffer solution
      and diluted human serum, respectively. The presented biosensor scheme requires a
      small amount of the sample down to 10 MUL in human serum and a short incubation
      time (15 min) of the sample solution containing NSE, enabling less invasive and
      rapid detection of NSE. This is the first example of the sensitive sandwich
      immunoassay demonstrated by using a plasmonic chip for the measurement of the
      sample dissolved in a complex medium with a rear side coupling method, which
      progresses the universal use of the SPF biosensors with a disposable plasmonic
      chip.

PMID- 29327756
TI  - Isomeric and hybrid ferrocenyl/cyrhetrenyl aldimines: a new family of
      multifunctional compounds.
AB  - The synthesis and characterization of two novel and isomeric hybrid
      ferrocenyl/cyrhetrenyl aldimines [(eta5-C5H5)Fe{(eta5-C5H4)-CH[double bond,
      length as m-dash]N-(eta5-C5H4)}Re(CO)3] (1) and [(eta5-C5H5)Fe{(eta5-C5H4)
      N[double bond, length as m-dash]CH-(eta5-C5H4)}Re(CO)3] (2) are reported. Their X
      ray crystal structures reveal that both adopt the E form. However, molecules of 1
      and 2 differ in the relative arrangement of the "Fe(eta5-C5H5)" and "Re(CO)3"
      units (anti in 1 and syn in 2). This affects the type of intermolecular
      interactions, the assembly of the molecules and therefore their crystal
      architecture. Comparative studies of their electrochemical, spectroscopic and
      photo-physical properties have allowed us to clarify the effect produced by the
      location of the organometallic arrays (ferrocenyl or cyrhetrenyl) on electronic
      delocalization, the proclivity of the metals to undergo oxidation and their
      emissive properties. Theoretical studies based on Density Functional Theory (DFT)
      calculations on the two compounds have also been carried out in order to
      rationalize the experimental results and to assign the bands detected in their
      electronic spectra. The cytotoxic activities of compounds 1 and 2 against human
      adenocarcinoma cell lines [breast (MCF7 and MDA-MB-231) and colon (HCT-116)]
      reveal that imine 2 has a greater inhibitory growth effect than 1 and it is ca.
      1.8 times more potent than cisplatin in the triple negative MDA-MB 231 and in the
      cisplatin resistant HCT-116 cell lines. A comparative study of their effect on
      the normal and non-tumour human skin fibroblast BJ cell lines is also reported.

PMID- 29327758
TI  - A computational analysis of pro-angiogenic therapies for peripheral artery
      disease.
AB  - Inducing therapeutic angiogenesis to effectively form hierarchical, non-leaky
      networks of perfused vessels in tissue engineering applications and ischemic
      disease remains an unmet challenge, despite extensive research and multiple
      clinical trials. Here, we use a previously-developed, multi-scale, computational
      systems pharmacology model of human peripheral artery disease to screen a diverse
      array of promising pro-angiogenic strategies, including gene therapy,
      biomaterials, and antibodies. Our previously-validated model explicitly accounts
      for VEGF immobilization, Neuropilin-1 binding, and weak activation of VEGF
      receptor 2 (VEGFR2) by the "VEGFxxxb" isoforms. First, we examine biomaterial
      based delivery of VEGF engineered for increased affinity to the extracellular
      matrix. We show that these constructs maintain VEGF close to physiological levels
      and extend the duration of VEGFR2 activation. We demonstrate the importance of
      sub-saturating VEGF dosing to prevent angioma formation. Second, we examine the
      potential of ligand- or receptor-based gene therapy to normalize VEGF receptor
      signaling. Third, we explore the potential for antibody-based pro-angiogenic
      therapy. Our model supports recent observations that improvement in perfusion
      following treatment with anti-VEGF165b in mice is mediated by VEGF-receptor 1,
      not VEGFR2. Surprisingly, the model predicts that the approved anti-VEGF cancer
      drug, bevacizumab, may actually improve signaling of both VEGFR1 and VEGFR2 via a
      novel 'antibody swapping' effect that we demonstrate here. Altogether, this model
      provides insight into the mechanisms of action of several classes of pro
      angiogenic strategies within the context of the complex molecular and
      physiological processes occurring in vivo. We identify molecular signaling
      similarities between promising approaches and key differences between promising
      and ineffective strategies.

PMID- 29327759
TI  - Bi and trinuclear complexes in palladium carboxylate-assisted C-H activation
      reactions.
AB  - The role of polynuclear species in C-H activations assisted by palladium
      carboxylates has not been clear so far. The summary of the key findings covering
      this issue shows its important role under certain conditions. However, much more
      effort is necessary for a deeper understanding of the whole issue.

PMID- 29327760
TI  - Composition, thickness and properties of grafted copolymer brush coatings
      determined by ellipsometry: calculation and prediction.
AB  - The composition, thickness and properties of poly(4-vinylpyridine-co
      oligo(ethylene glycol)ethyl ether methacrylate246) [P(4VP-co-OEGMA246)] copolymer
      grafted brush coatings attached to glass were studied in the dry and swollen
      states using ellipsometry. These measured data are in good agreement with
      predicted (estimated) changes in the amount of water, refractive index and
      thickness of the grafted copolymer brush coatings on swelling. For POEGMA brushes
      the thickness of the coatings on swelling at 20  degrees C can be more than
      double, in contrast to P4VP where those changes are insignificant. The presence
      of 4VP units in the structure of the P(4VP-co-OEGMA246) copolymer grafted brushes
      significantly decreases the hydration degree even for coatings with very low
      concentrations of 4VP units.

PMID- 29327761
TI  - Evaluation of clinical reasoning teaching for third year medical students.
AB  - INTRODUCTION: Clinical reasoning teaching is an educational method based on
      learning and contextualized education.The aim of this study was to determine the
      value of clinical reasoning teaching sessions, from the perspective of third year
      medical students using a self-administered questionnaire. METHOD: Two successive
      groups of nine students (a total of 18 students) participated in this study.They
      had anexternship in the cardiology department of HabibThameur hospital during
      amonth.An anonymous evaluation self-administered questionnaire was submitted to
      the two groups at the end of the traineeshipperiod. RESULTS: The average scores
      given by students for the items "quality of education", "workload", "atmosphere",
      "interest in teaching sessions"and "acquisition of new clinical knowledge" were
      greater than 8/10. Exposed health problem to be solved has attracted the interest
      and the motivation of 16 students and prompted 15 others to do further
      research.Fourteen students opted for clinical reasoning teaching as the preferred
      teaching method for optimal memorization.Thirteen students have found a real
      contribution ofreasoning teaching in the management of relationship with the
      patient.All students assumed that clinical reasoning meetings session should be
      more frequently usedduring the internship period. CONCLUSION: Clinical reasoning
      teaching session appears to be widely desired by medical students.

PMID- 29327762
TI  - The role of the pathologic exam in the acute exacerbations of the interstitial
      pneumonia.
AB  - Acute exacerbation of interstitial pneumonia is a new terminology with recent
      debated criteria. Its prognosis is bad and its management remains non consensual.
      This lack of consensus seems to be due to the lack of knowledge concerning the
      physiopathologic phenomenon. This lack of knowledge results in few efficient
      therapeutics. The diagnosis of acute exacerbation is challenging for clinicians
      and the real place of the pathologic exam remains unknown. Our aim was to assess
      the different situations faced by the pathologists by emphasizing their real
      role.

PMID- 29327763
TI  - Internal transfistulary drainage for intrabiliary rupture of hydatid cyst of the
      liver: Analysis of the indications and the results. Report of 50 cases.
AB  - BACKGROUND: The rupture of hydatid cyst of the liver into the biliary tracts
      through a large fistula is one of the most difficult complications to treat. The
      techniques are various and each has its own morbidity. Internal transfistulary
      drainage is a surgical method of treatment of hydatid cysts of the liver opening
      in the biliary tract. AIMS: The aim of this study was to identify the risk
      factors of specific postoperative complications of this surgical technique
      Methods: During the period's study, 823 patients with liver hydatid cyst were
      operated. 86 (11 %) of them were opened in the bile ducts through a large
      fistula. 50 patients (58 %) had internal transfistulary drainage. RESULTS: The
      sex ratio was 1.6. The population was young with an average age of 40.8 years.
      The most frequent clinical feature of the opening in the biliary tract was acute
      cholangitis (42 %). The most common location of hydatid cyst was at the hepatic
      dome. The pericyst was flexible in only 62 % of cases. Thick pericysts were made
      flexible in 20% of cases and partly resection of protruding dome was made in 36 %
      of cases. Specific morbidity rate was 16% with no mortality. The uni and
      multivariate analysis had identified as risk factors for specific complications:
      the thick pericyst (P = 0.04), a size of the residual cavity >= 9cm; non
      visualization of the residual cavity on the post operative cholangiography was of
      borderline statistical significance (P = 0.049). CONCLUSION: The internal
      transfistulary drainage is an easy and reliable surgical technique, its morbidity
      is low. It's indicated in the cases of large fistula with a thin pericyst and a
      diameter of the residual cavity less than 09 cm. Making thick pericyst flexible
      is a false security for the indication of internal transfistulary drainage and
      the non visualization of the residual cavity on the post operative
      cholangiography impose more frequent control for these patients since they are at
      risk of complications.

PMID- 29327764
TI  - Diagnosis and management of idiopathic facial palsy in children.
AB  - Idiopathic or Bell's palsy is an acute peripheral-nerve palsy involving the
      facial nerve. The disorder is quite infrequent under the age of 10 years. The
      proposed etiologies of Bell's palsy include ischemic neuropathy and vascular
      diseases. This case series presents five children with Bell's palsy. The
      epidemiologic, diagnostic and therapeutic measures were summarized. The evolution
      regarding especially the facial motricity was detailed. The results about the
      role of some thrombophilic polymorphisms suggest a probable involvement of factor
      V haplotype, MTHFR and factor XIII in the etiology of Bell's palsy in five
      Tunisian children.

PMID- 29327765
TI  - Child mortality infected with HIV1 followed in 40 pediatric care sites in Togo.
AB  - INTRODUCTION: The infection in pediatric HIV is the reason a lot of problems in
      Africa The objective of our study were to identify factors associated with
      mortality during follow-up of children receiving antiretroviral therapy in Togo.
      METHODS: It was a cross-sectional study of 870 children aged files from 7 weeks
      to 15 years infected with HIV on antiretroviral treatment, covering the period 1
      January 2001 to 31 December 2010 taking in 40 sites medical management in Togo.
      Data processing was done with the software Epi-Info 6.04d and duplicates were
      treated by the Software ESOPE. RESULTS: All patients were infected with HIV-1. In
      total forty six (46) deaths is 5.29% of the overall cohort were reported in our
      series. The lethality of the overall cohort followed for 60 months was 5.29%. The
      survival rate of the overall effective monitoring in our study was 89.2%. Fifty
      eight percent (58%) of deaths had affected children in a state of severe
      malnutrition and forty two percent (42%) in a state of moderate malnutrition.
      Sixty two percent (62%) of children under HAART treatment died benefited
      monitoring a psychologist. CONCLUSION: The diagnostic inadequacies of pediatric
      HIV strike the prognosis of infected children. Efforts still needs to be done to
      improve the load take pediatric HIV in Togo.

PMID- 29327766
TI  - Contribution of ultrasound in the study of ovarian fibrothecomas: a series of 47
      cases.
AB  - INTRODUCTION: Ovarian fibro-thecoma are rare presenting 1 to 4, 7%of ovarian
      organictumors. These tumors are of stromal origin and contain varied proportion
      of fusiform connective tissue cells and theca cells. They mainly affect
      menopausal or perimenopausal women. This tumor is benign in most cases and may be
      responsible for hormone secretion. OBJECTIVES: Study the epidemiological and
      clinical data of patients with ovarian fibro-thecoma, analyze ultrasonographic
      characteristics of these tumors,and evaluate the sensitivity and specificity of
      pelvic ultrasound in ovarian fibro-thecoma approach. METHODS: A retrospective
      study of 47 patients who underwent surgical treatment for ovarian fibro-thecoma
      was performed. Data were collected in our department of gynecologyand obstetrics
      A within Charles Nicole hospital in Tunis, over a period of 18 years between
      January 1994 and December 2012. For each of our observations, we analyzed the
      clinical and para-clinical data, including U.S. characteristics and available MRI
      data with confrontation to the final histological results. RESULTS: The average
      age of patients was 45.2 years. The average gravidity was 4 and the mean parity
      was 3. . Thirty-eight of our patients were postmenopausal (80.85%). Ovarian tumor
      was discovered incidentally in 11 cases and on the occasion of functional
      symptoms in 36 cases including pelvic pain in 18 cases. Physical examination
      revealed a pelvic mass in 17 patients and pelvic-abdominal in 14 patients. All
      patients underwent a pelvic ultrasound. . Ultrasound identified 49 tumors (2
      cases of bilateral tumors). Average size of tumors was 10, 05 cm (4 to 30 cm). )
      . Ovarian tumor was echogenic in 9 cases (18.36%), hypoechoic in 14 cases
      (28.47%), mixed in 14 cases (28.47%) and anechoic in 12 cases (24.49%). The tumor
      was found to be solid in 27 cases (55.1%); cystic in 8 cases (16.3%) and solido
      cystic in 14 cases (28.6%).It was compartmentalized in 10 cases. Extra cystic
      vegetations were found in 2 patients. The tumor was nonvascularized at color
      Doppler in 47 cases (95.9%) and slightly vascularized in 2 cases (4.1%). Intra
      peritoneal effusion was objectified in 15 cases. The diagnosis of ovarian fibro
      thecoma was raised based on U.S in 25 cases (51.02%) before surgery .MRI was
      performed in four cases. All patients underwent surgery. We performed laparotomy
      in 36 cases and laparoscopy in 11 cases. By laparotomy were performed a total
      hysterectomy with bilateral oophorectomy in most cases (26 patients). By
      laparoscopy we did lumpectomy in all cases. . The final pathologic examination
      revealed 19 fibromas, 14cystadenofibromas and 14 fibrothecomas. CONCLUSION: The
      paraclinical exploration of ovarian fibro-thecoma isbased, as all ovarian tumors,
      on ultrasound examination. The most typical features are images of solid tumors
      with regular contours, echogenic or mixed with the presence of streakedshadows.

PMID- 29327767
TI  - Triple negative breast cancer: A clinico-epidemiological and histopronostic study
      of 90 cases.
AB  - PURPOSE: The aim of this study was to describe the clinico-epidemiological and
      histopronostic characteristics of triple negative breast cancer (TNBC) and to
      evaluate the therapeutic results in tunisian women. METHODS: We reported the
      results of a retrospective study including 90 patients treated for TNBC between
      Junuary 2008 and December 2009 in the Salah Azaiz Institute of Tunis. RESULTS:
      TNBCoccured in 14% of diagnosed breast cancers. The mean age at diagnosis was
      53.67 years. Family history of breast cancer was reported in 10% of cases.The
      majority of tumors were classified as T2 (41%) and associated with invasive
      ductal carcinoma histological type (99%) and SBR grade-II (54%). Tumor lymph node
      metastases were detected in 44% of patients.Among operated patients, 46% of
      patients underwent conservative surgery and 54% radical surgery. Chemotherapy and
      postoperative radiotherapy were given in97% and 80%of patients, respectively.
      After a median follow-up of 33.51 months, 61% of patients remained free of
      disease, 12% hadloco-regional recurrence, 9% had disease progression during
      chemotherapy and 21% developed systemic disease. CONCLUSION: TNBC diagnosis is
      often made in the advanced stage and has a tendency to recur after treatment. The
      variable responseto chemotherapy is due to the molecular tumor heterogeneity. The
      development of targeted therapies is necessary to improve outcome of
      chemoresistant TNBC.

PMID- 29327768
TI  - Anaphylaxis in an emergency department: Epidemiology, clinical features and
      management.
AB  - INTRODUCTION: Studies report that anaphylaxis was under-diagnosed in emergency
      department (ED) and emergency management was often in disagreement with
      international recommendations. AIM OF THE STUDY: The aim of this study was to
      describe the epidemiology, clinical features, management and outcome of patients
      with anaphylaxis presenting to an ED. METHODS: Prospective, observational study
      over four years (June 2010 to May 2014). INCLUSION CRITERIA: patients (> 14 years
      of age) presenting consecutively to the ED with the diagnosis of anaphylaxis.
      Collection of epidemiological, clinical and therapeutic parameters Results:
      During the study, 239 patients were enrolled. Mean age = 40+/-15 years. Sex
      ratio=0.8.  History of anaphylaxis was reported in 40% of cases. Clinical
      features n (%): cutaneous features 229 (96), cardiovascular features 124 (52),
      respiratory features 127 (53), gastrointestinal features 48 (20) and neurologic
      features 4 (10). Most common allergens: drugs 62%, food 24% and insects 4%. No
      causes were apparent in 8% of cases. An anaphylactic shock was recorded in 73
      patients (31%). Adrenaline was used in 83%of patients, intravenously in 31%. 
      Corticosteroids and histamine H1 antagonist were prescribed in 98 and 51%
      respectively. Biphasic reactions were reported in three patients. There was no
      death cases registered. CONCLUSION: Our results showed that the prevalence of
      anaphylaxis was low.This demonstrates that anaphylaxis is a situation which
      remains underestimated. It is therefore imperative to conduct prospective
      multicenter studies in emergency services for better determination of its impact
      and its risk factors.

PMID- 29327769
TI  - Drug-adverse related events in emergency department : Epidemiological,clinical
      profile and prognosis.
AB  - INTRODUCTION: Adverse-drug events (ADe) are frequent in emergency medicine and
      remain misdiagnosed depending on the clinical polymorphism and the underlying
      comorbidities. Older patients with multiple comorbidities and polypharmacy are
      more frequently affected and makes poor prognosis. AIM OF THE STUDY: The aim of
      this study was to evaluate the epidemiology of ADe in the emergency department
      (ED) visits and to identify the prognostic value mortality within 30 days.
      METHODS: Prospective, monocentric study. Patients were included if they met
      criteria of aADe. We evaluated severity and mortality at 30 days. Moreover,
      misuse and preventabilty were studied. RESULTS: We included 159 cases within
      113,272 ED visits. Mean age = 64 +/- 19 years, sex ratio =0.6.The average number
      of drugs was 4.5 +/- 3. Polymedication was found in 54%. In 10 cases, the
      prescription contained twice the same molecule. A double ADe was found in 11
      patients. We identified 55 cases of misuse, 94% of them were due to physician. An
      interaction was found in 23 patients. Improper prescription with age, renal
      function or presence of contra-indications was found in 46 patients. In 41%
      cases, ADR events were preventable. An ADR event was considered severe in 44% of
      cases and 30-Days mortality's rate was 9.4%. Drugs n (%): Anticoagulants
      53(34,6); Antihypertensive 29(19); Antiarrhythmic 15(10). Multivariate analysis
      of mortality at day 30: Misuse and polyapthology were independent predictors;
      Respective Odds ratios: (OR: 2.6; 95% CI [1.25-5.38]; p=0,001) and (OR 2.31; 95%
      CI [1,16 - 4,61]; p=0,017). CONCLUSION: Drug-related ED visits are common in
      elderly. ADe is severe in 44% cases and preventable in 41%. Mortality rate was
      9,4%. Misuse, polypharmacy and comorbidities were independent predictors of
      severity and mortality.

PMID- 29327770
TI  - The head to foot screw fixation. A new technique of percutaneous screw fixation
      of the scaphoid bone.
AB  - OBJECTIVES: Many techniques have been described for screw fixation of the
      scaphoid bone. The approach is either proximal or dorsal. A new percutaneous
      technique is presented by the authors called the head to foot screw fixation.
      Indications and results are evaluated. METHODS: It is a percutaneous technique
      with fixation of the scaphoid bone by two screws introduced in an opposite
      direction: a proximal screw and a distal screw. No postoperative immobilization
      was necessary. A prospective study was conducted in 40 patients over a period of
      three years. The average age was 25 years with extremes of 14 and 44 years. This
      technique was practiced in fractures (30 cases) and nonunion (10 cases) in which
      the localization was proximal, corresponding to Schernberg types I, II and III.
      Forms associated with perilunate dislocation of the carpus were excluded from the
      study. RESULTS: The results were analysed with a mean of 8 months (6-30). Union
      was obtained in all the cases. No tendon injury related to percutaneous approach
      was noted. The technique required a learning curve with progressive decrease in
      operative time from 45 to 15 minutes. It was necessary in two cases to change
      protruding screws which were not diagnosed during the first intervention.
      Percutaneous screw fixation was achieved again in both cases.   Conclusions: The
      combination in our experience of two screws allowed us to prevent rotation around
      the unthreated area of a single screw. Our technique, bringing together the head
      to the foot of the screw, reduces the crowding at the proximal part of the
      scaphoid bone. This non-invasive method permitted early mobilization with no pain
      until biological union.

PMID- 29327771
TI  - Inherited ADMATS13 deficiency: When to evoke the in the newborn?
AB  - Inherited ADMATS13 or Upshaw-Schulman syndrome (USS) is caused by the deficiency
      of the Von Willebrand factor-cleaving protease. It is characterized by recurrent
      episodes of thrombocytopenia reversible by fresh frozen plasma (FFP) infusions,
      microangiopathic hemolytic anemia, and microvascular thrombosis leading to
      ischemic damage of multiple organs with end stage renal failure, or neurological
      sequelae in the absence of appropriate treatment. The typically reported features
      of USS in neonates are severe jaundice with hyperbilirubinemia, thrombocytopenia
      and /or combs negative hemolytic anemia, and an increased creatinine.We presented
      a clinical case of USS with unusual features, which delayed the diagnosis.USS was
      declared at sixth hours of life with diffuse hemorrhage related to an early
      neonatal infection. Analysis of the plasma, at the age of 20 months, revealed low
      ADAMTS13 activity in the patient (<1%).Inherited ADMATS13 deficiency
      manifestations may overlap with other conditions, which may delay diagnosis and
      lead to visceral and neurological damage. The diagnosis should be, early
      considered in some clinical conditions: discrepancy between the severity of a
      hemorrhagic syndrome and thrombocytopenia, recurrence, resistance to symptomatic
      treatment. The diagnosis can be suggested by the normalization of platelet count
      after FFP transfusions.

PMID- 29327772
TI  - Chilaiditi's sign (or syndrome).

PMID- 29327773
TI  - Erosive erythema multiforme of the oral mucosa with acantholysis et circulating
      autoantibodies.

PMID- 29327774
TI  - Lung herniation : a case report of a spontaneous cervical hernia.

PMID- 29327776
TI  - A rare cause of dyspnea in adulthood: Bochdalek hernia.

PMID- 29327775
TI  - Renal carcinoma associated to acquired cystic renal disease.

PMID- 29327777
TI  - The Use of Acellular Dermal Matrices (ADM) in Breast Reconstruction: A Review.
AB  - The use of acellular dermal matrices (ADM), sometimes referred to as
      extracellular matrix (ECM), has become an interesting aspect of breast
      reconstruction. A great deal of literature is available, totaling over 7000 ADM
      based reconstructions. Most often, ADMs are used in a skin sparing mastectomy
      (SSM) scenario, although heterologous breast augmentation with a sub-pectoral
      fixation may also require an ADM application. Their use has become an attractive,
      but expensive option. Available data shows head to head comparisons between
      individual ADMs to be mostly retrospective in nature with only a few prospective
      trials available. Points of interest include postoperative hematoma,
      postoperative skin irritation, infection, red breast syndrome, and revision
      surgery. This work will, therefore, highlight the individual properties of ADMs
      used in breast reconstruction and compare the available data on complication
      rates and costs for these devices.

PMID- 29327778
TI  - Impact of Physical Activity and Body Mass Index in Cardiovascular and
      Musculoskeletal Health: A Review.
AB  - Due to an increasing elderly population coupled with a growing obesity epidemic,
      there has been an increased prevalence in cardiovascular and musculoskeletal
      diseases. This has led to an increased burden in healthcare expenditures, now
      estimated to be over 17.8% of gross domestic product. As a result, physical
      activity has been increasingly encouraged due to its potential prophylactic
      effects on health. Recent reports have demonstrated a relationship between
      physical activity and body mass index (BMI) on cardiovascular and musculoskeletal
      health. However, the effect of the combination of the two have not been reported.
      Therefore, the purpose of this review was to assess the effect of various levels
      of physical activity on: 1) cardiovascular disease risk; and 2) the development
      of musculoskeletal disease (osteoarthritis [OA]) when accounting for various
      levels of BMIs. A total of 143 abstracts were identified for cardiovascular
      health and 55 abstracts for musculoskeletal health. Upon review, 11 reports were
      included for final evaluation. Despite patient BMI, physical activity was
      associated with a decreased risk of cardiovascular events. Additionally, moderate
      levels of physical activity were demonstrated to be protective against the
      development of OA; however, the levels of physical activity necessary to be
      beneficial were not fully elucidated. This suggests that the prophylactic effects
      of physical activity were maintained despite patient BMI. Future studies are
      needed to explore the appropriate levels of physical activity for optimal
      effectiveness when stratifying by patient BMI.

PMID- 29327779
TI  - Locally delivered ethyl-2,5-dihydroxybenzoate using 3D printed bone implant for
      promotion of bone regeneration in a osteoporotic animal model.
AB  - Osteoporosis is a disease characterized by low bone mass, most commonly caused by
      an increase in bone resorption that is not matched by sufficient bone formation.
      The most common complications of postmenopausal osteoporosis are bone-related
      defects and fractures. Fracture healing is a multifactorial bone regeneration
      process, influenced by both biological and mechanical factors related to age,
      osteoporosis and stability of the osteosynthesis. During the treatment of bone
      defects in osteoporotic conditions, imbalanced bone remodeling is the leading
      cause for implant failure. To overcome these problems, ethyl-2,5
      dihydroxybenzoate (E-2,5-DHB), a drug that promotes bone formation and inhibits
      bone resorption, was used. E-2,5-DHB-incorporating titanium (Ti) implants using
      poly(lactic-co-glycolic acid) (PLGA) coating for local delivery of E-2,5-DHB were
      developed and the effects on bone healing of femoral defects were evaluated in an
      osteoporotic model. The release of E-2,5-DHB resulted in decreased bone
      resorption and increased bone formation around the implant. Thus, it was
      confirmed that, in the osteoporotic model, bone healing was increased and implant
      fixation was enhanced. These results suggested that E-2,5-DHB-coated Ti implants
      have great potential as an ultimate local drug delivery system for bone tissue
      scaffolds.

PMID- 29327780
TI  - Systematic review with meta-analysis: effectiveness and tolerability of
      interferon-free direct-acting antiviral regimens for chronic hepatitis C genotype
      1 in routine clinical practice in Asia.
AB  - BACKGROUND: Direct-acting antiviral (DAA) regimens have shown high efficacy and
      tolerability for patients with HCV genotype 1/1b (GT1/1b) in clinical trials.
      However, robust real-world evidence of interferon (IFN)-free DAA treatment for
      HCV GT1-infected patients in Asia is still lacking. AIM: To systematically review
      and meta-analyse the effectiveness and tolerability of IFN-free DAA therapy for
      HCV GT1 infection in Asia. METHODS: We included studies that enrolled adult
      patients with HCV GT1 infection in routine clinical practice in Asia, using IFN
      free DAA regimens, and reported sustained virological response (SVR) after 12/24
      weeks end-of-treatment by 31 May 2017. The pooled SVR rates were computed with a
      random-effects model. Subgroup analysis and meta-regression as previously
      registered in PROSPERO were performed to determine how pre-planned variables
      might have affected the pooled estimates. RESULTS: We included 41 studies from
      eight countries and regions, comprising of 8574 individuals. The pooled SVR rates
      for GT1 were 89.9% (95% CI 88.6-91.1, I2  = 55.1%) with daclatasvir/asunaprevir
      (DCV/ASV) and 98.1% (95% CI 97.0-99.0, I2  = 41.0%) with ledipasvir/sofosbuvir +/
      ribavirin (LDV/SOF +/- RBV). Baseline cirrhosis but not prior treatment history
      and age, attenuated the effectiveness of both regimens. Baseline resistance
      associated substitutions (RASs) severely attenuated SVR of DCV/ASV (65.4% vs
      94.3%, P < 0.001) and only minimally with LDV/SOF +/- RBV (94.5% vs 99.2%, P =
      0.003). Patients with renal dysfunction treated with DCV/ASV showed a higher SVR
      rate (93.9% vs 89.8%, P = 0.046). Patients with hepatocellular carcinoma (HCC)
      LDV/SOF +/- RBV achieved a lower SVR than those without HCC (94.1% vs 98.7%, P =
      0.001). CONCLUSION: All oral DAA treatment of HCV GT1 resulted in high cure rates
      in Asian patients in routine clinical practice setting including elderly patients
      and those with end-stage renal disease.

PMID- 29327781
TI  - Treatment with proton pump inhibitors is associated with increased mortality in
      patients with pyogenic liver abscess.
AB  - BACKGROUND: Proton pump inhibitors (PPI) are often used in patients with gastro
      esophageal reflux and peptic ulcer disease. A higher risk for infectious diseases
      and for pyogenic liver abscess has been reported in patients with prolonged PPI
      intake. Although many patients have ongoing PPI treatment after diagnosis of
      liver abscess, there are no data available that focus on the prognostic impact of
      PPI treatment in these patients. AIM: To analyse the effect of PPI treatment on
      mortality in patients with pyogenic liver abscesses. METHODS: Between January
      2005 and March 2017, one hundred and eighty-one patients with pyogenic liver
      abscess were retrospectively included in this analysis. Medical records including
      PPI treatment, microbiological and imaging data were reviewed. The primary
      endpoint was index mortality and predictive factors were analysed using uni- and
      multivariate logistic regression models. RESULTS: One hundred patients with
      pyogenic liver abscess (55.2%) were treated with PPI compared to 81 patients
      (44.8%) without PPI treatment. In both patient cohorts, enterococcus spp. and
      streptococcus of the anginous group were the most common pathogens identified.
      Patients with PPI treatment had significantly higher index mortality compared to
      patients without PPI treatment (30.0% vs 11.1%, P = 0.003). After adjusting for
      comorbidities PPI remained an independent predictive factor with an OR of 2.56
      (1.01-6.46, P = 0.036). CONCLUSIONS: PPI treatment is associated with higher
      index mortality in patients with pyogenic liver abscess. Therefore, critical
      evaluation of the indication for PPI treatment is particularly important in
      patients at high risk for pyogenic liver abscess.

PMID- 29327783
TI  - Nonsurgical management of human immunodeficiency virus-associated parotid cysts:
      A systematic review and meta-analysis.
AB  - BACKGROUND: The purpose of this clinical review was to analyze the effectiveness
      of nonsurgical management options for human immunodeficiency virus (HIV)
      associated parotid cysts. METHODS: We conducted systematic and meta-analysis
      reviews. Primary outcomes were complete or partial responses. RESULTS: Systematic
      review identified 12 relevant studies. The average rates of complete response for
      antiretroviral therapy (ART), sclerotherapy, and fine-needle aspiration (FNA)
      were 52.8%, 55.5%, and 33.3%, respectively. Three radiotherapy studies, totaling
      104 patients, were included in a meta-analysis. Patients receiving high-dose
      therapy achieved complete and partial response rates of 65.8% (95% confidence
      interval [CI] 54.3%-76.2%) and 25.2% (95% CI 16.1%-36.3%), respectively. Patients
      receiving low-dose therapy achieved complete and partial response rates of 23.2%
      (95% CI 1.2%-60.9%) and 22.3% (95% CI 5.2%-87.8%), respectively. The rate of
      complete response was significantly greater for high-dose radiotherapy compared
      to low-dose (P < .001). CONCLUSION: Among nonsurgical treatment modalities for
      HIV-associated parotid cysts, radiotherapy has the highest number of reported
      outcomes in the literature and our analysis suggests that higher dose
      radiotherapy has higher rates of achieving complete response.

PMID- 29327784
TI  - Transoral robotic surgery for oropharyngeal carcinoma: Surgical margins and
      oncologic outcomes.
AB  - BACKGROUND: This study presents oncologic outcomes after transoral robotic
      surgery (TORS) +/- adjuvant therapy for oropharyngeal squamous cell carcinoma
      (SCC). METHODS: Three hundred fourteen patients undergoing TORS +/- adjuvant
      therapy for oropharyngeal SCC from May 1, 2007, to May 31, 2015, are analyzed.
      RESULTS: Median follow-up was 3.3 years (interquartile range [IQR] 1.8-5.3 years;
      range 1 day to 9.3 years). Estimated locoregional recurrence-free survival,
      distant metastasis-free survival (DMFS), overall survival (OS), and cancer
      specific survival (CSS) rates (95% confidence interval [CI] number still at risk)
      at 5 years after surgery were 92% (88-95; 92), 90% (86-94; 92), 86% (82-92; 98),
      and 94% (91-97; 98), respectively. Negative margins were achieved in 98% of
      cases. The adult comorbidity evaluation (ACE)-27 comorbidity index, human
      papillomavirus (HPV) status, pathologic N classification, and number of attempts
      to clear margins were associated with death due to cancer (P = .003, P = .002, P
      = .030, and P = .002, respectively). CONCLUSION: The need to take >=2 margins to
      achieve resection portends an increased risk of locoregional recurrence and death
      due to disease in oropharyngeal SCC.

PMID- 29327782
TI  - Development of manganese-enhanced magnetic resonance imaging of the rostral
      ventrolateral medulla of conscious rats: Importance of normalization and
      comparison with other regions of interest.
AB  - Spinally projecting neurons in the rostral ventrolateral medulla (RVLM) are
      believed to contribute to pathophysiological alterations in sympathetic nerve
      activity and the development of cardiovascular disease. The ability to identify
      changes in the activity of RVLM neurons in conscious animals and humans,
      especially longitudinally, would represent a clinically important advancement in
      our understanding of the contribution of the RVLM to cardiovascular disease. To
      this end, we describe the initial development of manganese-enhanced magnetic
      resonance imaging (MEMRI) for the rat RVLM. Manganese (Mn2+ ) has been used to
      estimate in vivo neuronal activity in other brain regions because of both its
      paramagnetic properties and its entry into and accumulation in active neurons. In
      this initial study, our three goals were as follows: (1) to validate that Mn2+
      enhancement occurs in functionally and anatomically localized images of the rat
      RVLM; (2) to quantify the dose and time course dependence of Mn2+ enhancement in
      the RVLM after one systemic injection in conscious rats (66 or 33 mg/kg,
      intraperitoneally); and (3) to compare Mn2+ enhancement in the RVLM with other
      regions to determine an appropriate method of normalization of T1 -weighted
      images. In our proof-of-concept and proof-of-principle studies, Mn2+ was
      identified by MRI in the rat RVLM after direct microinjection or via retrograde
      transport following spinal cord injections, respectively. Systemic injections in
      conscious rats produced significant Mn2+ enhancement at 24 h (p < 0.05).
      Injections of 66 mg/kg produced greater enhancement than 33 mg/kg in the RVLM and
      paraventricular nucleus of the hypothalamus (p < 0.05 for both), but only when
      normalized to baseline scans without Mn2+ injection. Consistent with findings
      from our previous functional and anatomical studies demonstrating subregional
      neuroplasticity, Mn2+ enhancement was higher in the rostral regions of the RVLM
      (p < 0.05). Together with important technical considerations, our studies support
      the development of MEMRI as a potential method to examine RVLM activity over time
      in conscious animal subjects.

PMID- 29327785
TI  - The effect of partially exposed connective tissue graft on root-coverage
      outcomes: a systematic review and meta-analysis.
AB  - The aim of this systematic review was to compare the root-coverage outcomes of
      using a partially exposed connective tissue graft (CTG) technique with a fully
      covered CTG technique for root coverage. An electronic search up to February 28th
      , 2017, was performed to identify human clinical studies with data comparing
      outcomes of root coverage using CTG, with and without a partially exposed graft.
      Five clinical studies were selected for inclusion in this review. For each study,
      the gain of keratinized gingiva, reduction of recession depth, number of surgical
      sites achieving complete root coverage, percentage of root coverage, gain of
      tissue thickness, and changes of probing depth and clinical attachment level were
      recorded. Meta-analysis for the comparison of complete root coverage between the
      two techniques presented no statistically significant differences. A
      statistically significant gain of keratinized tissue in favor of the sites with
      an exposed CTG and a tendency of greater reduction in recession depth were seen
      at the sites with a fully covered CTG. Based on the results, the use of a
      partially exposed CTG in root-coverage procedures could achieve greater gain in
      keratinized gingiva, while a fully covered CTG might be indicated for procedures
      aiming to reduce recession depth.

PMID- 29327786
TI  - Differential effects of experimental hyperthyroidism on declined immunity of
      broiler chicken.
AB  - Thyroid hormones (THs) are involved in the development of lymphoid organs and
      regulation of immune function in birds. However, their role as an immune
      modulator in the hyperthyroid state is still debatable. To explore the
      interrelationship of thyroxine (T4 ) and the immune system, chicks were divided
      into three groups. Group I was comprised of control birds, who received the basal
      diet while group II and III were given diets supplemented with 5 MUg and 10 MUg
      thyroxine/kg feed, respectively, from 15 to 28 days of age. Cell-mediated immune
      response was evaluated through in vitro abdominal macrophage phagocytosis assay,
      macrophage nitric oxide (NO) production, heterophil-to-lymphocyte (H:L) ratio and
      delayed-type hypersensitivity response against phytohemagglutinin (PHA). Humoural
      immune response was assessed through serum IgG and IgM antibody production
      against sheep red blood cells (SRBCs) and antibody production against infectious
      bronchitis virus (IBV). Sampling was carried out at 7, 14 and 21 days of
      treatment. Results have shown higher levels (p < .001) of circulating T4 in both
      treatment groups compared to the control group. There was a lower (p < .05)
      macrophage engulfment percentage, an increase in H:L ratio (p < .001) in treated
      birds, while their NO production remained higher (p < .05) in thyroxine
      supplemented groups after bacterial lipopolysaccharide stimulation. The humoural
      immune response revealed a significant decline (p < .001) in IgG, IgM antibody
      production against SRBCs but IBV circulating antibodies increased with age. In
      conclusion, hyperthyroidism has a strong co-relation with decreased immune
      performance of birds.

PMID- 29327787
TI  - Electrophile-Directed Diastereoselective Oxonitrile Alkylations.
AB  - Diastereoselective alkylation of prochiral oxonitrile dianions with secondary
      alkyl halides efficiently installs two contiguous stereogenic centers. The
      confluence of nucleophilic trajectory and the electrophile chirality causes
      distinct steric differences that allow efficient discrimination for one of the
      six possible conformers. Numerous oxonitrile-derived dianions efficiently
      displace secondary alkyl halides propagating the electrophile chirality to
      efficiently install two contiguous tertiary centers. The prevalence of chiral,
      secondary electrophiles makes the interdigitated alkylation of chiral
      electrophiles a particularly attractive route because the resulting oxonitriles
      are readily transformed into bioactive heterocycles.

PMID- 29327788
TI  - Teaching concept analysis to graduate nursing students.
AB  - AIM: To provide guidance to educators who use the Wilson (1963) concept analysis
      method, as modified by Walker and Avant (2011), in their graduate nursing
      curriculum BACKGROUND: While graduate nursing curricula often include a concept
      analysis assignment, there is a paucity of literature to assist educators in
      guiding students through this challenging process. DESIGN: This article details
      one way for educators to assist graduate nursing students in learning how to
      undertake each step of the Wilson (1963) concept analysis method, as modified by
      Walker and Avant (2011). DATA SOURCE: Wilson (1963) concept analysis method, as
      modified by Walker and Avant (2011). RESULTS: Using examples, this article walks
      the reader through the Walker and Avant (2011) concept analysis process and
      addresses those issues commonly encountered by educators during this process.
      CONCLUSION: This article presented one way of walking students through a Walker
      and Avant (2011) concept analysis. Having clear information about the steps
      involved in developing a concept analysis will make it easier for educators to
      incorporate it into their graduate nursing curriculum and to effectively guide
      students on their journey through this process.

PMID- 29327789
TI  - Imaging macrophage distribution and density in mammary tumors and lung metastases
      using fluorine-19 MRI cell tracking.
AB  - PURPOSE: The presence of tumor-associated macrophages (TAMs) correlates with
      breast cancer progression and metastatic spread. Metastasis-associated
      macrophages (MAMs) are also recruited to distant sites, where they support
      metastatic growth. In this study, we demonstrate that in vivo fluorine-19 (19 F)
      based MRI cell tracking can evaluate the density and distribution of macrophages
      within murine breast cancer tumors and associated metastases. METHODS: Three
      murine breast cancer cell lines with different metastatic potentials (4T1,
      168FARN, and 67NR) were implanted into the mammary fat pad in mice. In vivo whole
      body 19 F MRI was performed on tumor-bearing mice 24 hours post-intravenous
      injection of a perfluorocarbon (PFC) agent, which was taken up by macrophages in
      situ. RESULTS: TAMs were detected mainly in the periphery of primary tumors, and
      higher numbers of TAMs were detected in the more aggressive 4T1 tumors. Tumors
      had significantly greater 19 F spins/mm3 when they were smaller, suggesting more
      TAM infiltration in early-stage tumors. 19 F signal was observed within lung
      metastases in mice with 4T1 tumors, and fluorescence microscopy confirmed the
      presence of PFC-positive macrophages. CONCLUSION: This study shows for the first
      time proof of the ability to use MRI cell tracking to visualize MAMs in the
      lungs. The ability to detect and monitor the number of TAMs in individual tumors
      with 19 F MRI would allow for identification of breast tumors with heavy
      infiltration of TAMs and could be used as a biomarker for decisions about how to
      best treat these patients as well as for monitoring responses to therapy. Magn
      Reson Med 80:1138-1147, 2018. (c) 2018 International Society for Magnetic
      Resonance in Medicine.

PMID- 29327791
TI  - A Watershed Outlook for Pharmacotherapy in 2018.

PMID- 29327790
TI  - Iron Encapsulation in Water-in-Oil Emulsions: Effect of Ferrous Sulfate
      Concentration and Fat Crystal Formation on Oxidative Stability.
AB  - : Iron deficiency is a major global human health concern. Encapsulation of iron
      in functional food products may help to solve this problem. However, iron is
      highly reactive and may promote rapid lipid oxidation in fatty foods. In this
      study, the effect of ferrous sulfate (0.1 to 0.5 wt%) and rice bran stearin (0 or
      30 wt%) on the physical properties, oxidative stability, and encapsulation
      efficiency of 20 wt% water-in-oil (W/O) emulsions stabilized with polyglycerol
      polyricinoleate was investigated. In the presence of rice bran stearin crystals
      in the continuous oil phase, W/O emulsions had smaller mean droplet diameters (d
      ~ 250 nm) and better physical stability than its absence (d ~ 330 nm). An
      increase in the ferrous sulfate concentration in the water droplets led to a
      decrease in the oxidative stability of the W/O emulsions. However, the presence
      of rice bran stearin significantly (P <= 0.05) improved their oxidative
      stability. Moreover, addition of rice bran stearin also significantly (P <= 0.05)
      improved the encapsulation efficiency and delayed ferrous sulfate release from
      the W/O emulsions. The impact of pH and ionic strength on the encapsulation
      efficiency of the W/O emulsion was also investigated. Ionic strength affected the
      encapsulation efficiency much more than pH. The W/O emulsions created in the
      present study may be useful for the encapsulation and delivery of iron and other
      water-soluble nutrients into food products. PRACTICAL APPLICATION: Water-in-oil
      (W/O) emulsions may be used to encapsulate, protect, and deliver water-soluble
      bioactive compounds or nutrients into food products. In this study, W/O emulsions
      stabilized using an oil-soluble surfactant (polyglycerol polyricinoleate, PGPR)
      and fat crystal network (rice bran stearin) were shown to be useful for
      encapsulation and delivery of iron into foods. This strategy may be a promising
      approach to reduce iron deficiency, a major nutritional deficiency for people
      with inadequate food supplies.

PMID- 29327792
TI  - Tetrablock Metallopolymer Electrochromes.
AB  - Multi-block polymers are highly desirable for their addressable functions that
      are both unique and complementary among the blocks. With metal-containing
      polymers, the goal is even more challenging insofar as the metal properties may
      considerably extend the materials functions to sensing, catalysis, interaction
      with metal nanoparticles, and electro- or photochrome switching. Ring-opening
      metathesis polymerization (ROMP) has become available for the formation of living
      polymers using highly efficient initiators such as the 3rd generation Grubbs
      catalyst [RuCl2 (NHC)(=CHPh)(3-Br-C5 H4 N)2 ], 1. Among the 24 possibilities to
      introduce 4 blocks of metallopolymers into a tetrablock metallocopolymer by ROMP
      using the catalyst 1, two viable pathways are disclosed. The synthesis,
      characterization, electrochemistry, electron-transfer chemistry, and remarkable
      electrochromic properties of these new nanomaterials are presented.

PMID- 29327794
TI  - Meaningful aspects of the term 'mood stabilizer'.

PMID- 29327793
TI  - Who needs an implantable cardioverter-defibrillator? Controversies and
      opportunities after DANISH.

PMID- 29327795
TI  - Bipolar II: Comments on its validity and utility.

PMID- 29327796
TI  - Speech characteristics in the congenital and childhood-onset forms of myotonic
      dystrophy type 1.
AB  - BACKGROUND: Myotonic dystrophy type 1 (DM1) is a slowly progressive multi
      systemic disease with an autosomal-dominant inheritance caused by a mutation on
      chromosome 19 (19q13.3). AIMS: To explore speech characteristics in a group of
      individuals with the congenital and childhood-onset forms of DM1 in terms of
      intelligibility, speech-sound production, nasality and compensatory articulation.
      A further aim was to analyse whether speech characteristics were correlated to
      subforms of DM1 and if speech outcome could be related to muscle strength.
      METHODS & PROCEDURES: Fifty native Swedish speakers (7-29 years old) with the
      congenital and childhood-onset forms of DM1 and 13 healthy controls participated
      in the study. The intelligibility of spontaneous speech, speech-sound production 
      single-word and sentence repetition - including percentage consonants correct
      (PCC) and compensatory articulation, were evaluated by speech-language
      pathologists from video recordings. A nasometer and lip-force meter were used for
      objective evaluations of nasality and orofacial strength. OUTCOMES & RESULTS: In
      severe (n = 9) and mild congenital DM1 (n = 13), all participants had impaired
      intelligibility to some degree, while this applied to 79% of those with childhood
      DM1 (n = 28). PCC for bilabials were 53.9% in severe congenital DM1, 57.4% in
      mild congenital DM1 and 85.3% in childhood DM1; the corresponding results for
      dentals were 69.3%, 59.2% and 87.3%. Bilabials were most often compensated for
      with interdental or labiodental articulation. Dentals were substituted with
      interdental articulation. Velars were seldom affected. The mean nasalance score
      was high in the study group compared with controls and with normative data and
      the majority had weak lips. Maximum lip force, as well as the mean nasalance
      score, correlated significantly with the intelligibility score. CONCLUSIONS &
      IMPLICATIONS: The deviant production of bilabial consonants, interdental
      articulation and hypernasal speech are characteristic features of dysarthria in
      congenital and childhood DM1. Dysarthria is more frequent and more severe in
      congenital DM1 compared with childhood DM1. Most individuals with congenital DM1
      and childhood-onset DM1 will need speech therapy from a young age. For some
      children with incomprehensible speech or severe neurodevelopmental disorders,
      alternative and augmentative ways of communication will be part of the treatment.

PMID- 29327798
TI  - Severity of symptoms in mania-clinical guidelines and study design implications.

PMID- 29327797
TI  - Potassium and the use of renin-angiotensin-aldosterone system inhibitors in heart
      failure with reduced ejection fraction: data from BIOSTAT-CHF.
AB  - BACKGROUND: Hyperkalaemia is a common co-morbidity in patients with heart failure
      with reduced ejection fraction (HFrEF). Whether it affects the use of renin
      angiotensin-aldosterone system inhibitors and thereby negatively impacts outcome
      is unknown. Therefore, we investigated the association between potassium and
      uptitration of angiotensin-converting enzyme inhibitors (ACEi)/angiotensin
      receptor blockers (ARB) and its association with outcome. METHODS AND RESULTS:
      Out of 2516 patients from the BIOSTAT-CHF study, potassium levels were available
      in 1666 patients with HFrEF. These patients were sub-optimally treated with
      ACEi/ARB or beta-blockers and were anticipated and encouraged to be uptitrated.
      Potassium levels were available at inclusion and at 9 months. Outcome was a
      composite of all-cause mortality and heart failure hospitalization at 2 years.
      Patients' mean age was 67 +/- 12 years and 77% were male. At baseline, median
      serum potassium was 4.3 (interquartile range 3.9-4.6) mEq/L. After 9 months, 401
      (24.1%) patients were successfully uptitrated with ACEi/ARB. During this period,
      mean serum potassium increased by 0.16 +/- 0.66 mEq/L (P < 0.001). Baseline
      potassium was an independent predictor of lower ACEi/ARB dosage achieved [odds
      ratio 0.70; 95% confidence interval (CI) 0.51-0.98]. An increase in potassium was
      not associated with adverse outcomes (hazard ratio 1.15; 95% CI 0.86-1.53). No
      interaction on outcome was found between baseline potassium, potassium increase
      during uptitration, or potassium at 9 months and increased dosage of ACEi/ARB
      (Pinteraction  > 0.5 for all). CONCLUSION: Higher potassium levels are an
      independent predictor of enduring lower dosages of ACEi/ARB. Higher potassium
      levels do not attenuate the beneficial effects of ACEi/ARB uptitration.

PMID- 29327799
TI  - What is needed to prepare speech pathologists to work in adult palliative care?
AB  - BACKGROUND: Speech pathologists have a pivotal role in palliative care, assisting
      patients with swallowing and communication disorders, yet very little is known
      about the preparedness of speech pathologists to work in this field. AIMS: To
      investigate the preparedness of speech pathologists for working in palliative
      care. The term 'palliative care' was viewed as an encompassing umbrella term
      incorporating the management/reduction of symptoms and improvement in a person's
      quality of life at any point of the disease progression. METHODS & PROCEDURES:
      Participants were Australian-trained speech pathologists who provided adult
      palliative care services. An online questionnaire was used to gather both
      quantitative and qualitative data from practising speech pathologists.
      Qualitative data were analysed and interpreted using conventional content
      analysis. Descriptive statistics were analysed via the Statistical Package for
      the Social Sciences (SPSS) for Windows Version 22. Non-parametric tests (chi
      square and Mann-Whitney U-test) were used for further analysis. OUTCOMES &
      RESULTS: The majority (70%) of participants indicated that their university
      training did not prepare them to practice in palliative care. Participants who
      received palliative care education at the tertiary level were significantly more
      prepared to work with palliative patients than those who had not; however, only a
      minority (27%) had received such training. Just over half (57%) reported having
      completed post-university professional development in palliative care. The speech
      pathologist's role in palliative care was also highlighted, with speech
      pathologists outlining their contribution to the assessment of patients'
      communication and swallowing abilities. In addition, recommendations for
      palliative care content to be incorporated into university curriculum were
      suggested. CONCLUSIONS & IMPLICATIONS: Speech pathologists can make important
      contributions to end-of-life care, but there is much scope for improving the
      availability and quality of university and post-university palliative care
      training opportunities so that people receiving palliative care are best
      supported.

PMID- 29327800
TI  - The need for evaluating right ventricular adaptation and ventriculo-arterial
      coupling: reply.

PMID- 29327801
TI  - Tense and plural formation in Welsh-English bilingual children with and without
      language impairment.
AB  - BACKGROUND: Grammatical morphology has been shown to be problematic for children
      with specific language impairment (SLI) or developmental language disorder (DLD).
      Most research on this topic comes from widely spoken languages, such as English.
      Despite Welsh being the most extensively spoken indigenous in the UK after
      English, and Wales being the only official bilingual country in the UK, our
      knowledge about the morphosyntactic areas of Welsh that may pose problems for
      Welsh-speaking children with SLI is limited. Currently, Welsh-speaking speech and
      language therapists (SLTs) are heavily reliant on the use of informally
      translated English assessments. This can inadvertently result in a failure to
      take aspects of Welsh morphosyntax into account that are critical for the
      assessment and treatment of Welsh-speaking children. AIMS: This is the first
      study to examine how Welsh-English bilingual children of early school age with
      typical development (bi-TD) and with SLI (bi-SLI) perform on production tasks
      targeting verbal and nominal morphology in Welsh. We targeted areas of Welsh
      morphosyntax that could potentially be vulnerable for Welsh-speaking children
      with or at risk of language impairment, such as tense marking and plural
      formation, and assessed their diagnostic potential. METHODS & PROCEDURES: Twenty
      eight Welsh-dominant bilingual children participated in the study: 10 bi-SLI and
      18 bi-TD. They were administered three elicitation tasks targeting the production
      of verbal (compound and synthetic past tense) and nominal (plural) morphology in
      Welsh. OUTCOMES & RESULTS: The bi-SLI children performed worse than their bi-TD
      peers across all three tasks. They produced more uninflected verbs in the
      elicited-production task and were less likely to be prompted to produce the
      synthetic past, which is a concatenating, low-frequency form of the past tense.
      They also over-regularized less in the context of plural nouns, and when they
      did, they opted for high-frequency suffixes. CONCLUSIONS & IMPLICATIONS: By
      focusing on aspects of morphosyntactic development which are unique to Welsh, we
      have increased existing about how verbal and nominal morphology are acquired in
      Welsh-speaking bi-SLI and bi-TD children. The present results point towards
      productivity problems for Welsh-speaking bi-SLI children who are adversely
      influenced by low-frequency structures and fail to over-regularize in the context
      of verbal and nominal concatenating morphology. From a clinical perspective,
      targeting synthetic past-tense forms through a prompting task may be a promising
      assessment and intervention tool that future studies could explore further.

PMID- 29327802
TI  - An old debate still in the beta-phase?

PMID- 29327803
TI  - Myocardial oedema and congestive heart failure: one piece of the puzzle?

PMID- 29327804
TI  - HOME HF: an honest report of an (apparently) doable study.

PMID- 29327805
TI  - Benzonorcorrole NiII Complexes: Enhancement of Paratropic Ring Current and
      Singlet Diradical Character by Benzo-Fusion.
AB  - Fused benzene rings to antiaromatic compounds generally improve their stability
      but attenuate their antiaromaticity. The opposite case is now reported. NiII
      benzonorcorroles were synthesized and the effect of benzo-fusion on the
      antiaromaticity was elucidated. The benzo-fusion resulted in significant decrease
      of the HOMO-LUMO gaps and enhancement of the paratropic ring current effect.
      Furthermore, the introduction of the benzo groups induced singlet diradical
      character in the antiaromatic porphyrinoid.

PMID- 29327806
TI  - The determination of the carbonic anhydrases activators in vitro effect of mixed
      donor crown ethers.
AB  - Carbonic anhydrases (CAs) play an important function in various physiological and
      pathological processes. Therefore, many researchers work in this field in order
      to design and synthesize new drugs. Both inhibitors and activators of CAs, which
      are associated with the diagnosis and treatment of many diseases, are very
      important. The emergence of the use of CA activators in the treatment of
      Alzheimer has led many scholars to work on this issue. In this study, CA
      activators and inhibitors are determined. The crown ethers compounds (1, 2, 3, 6,
      7, 8, and 9) were found to cause activation on enzyme activities of hCA I and II.
      The AC50 values on hCA I and II of the compounds are in the range of 4.6565
      374.979 MUM. The 4 (IC50 ; 1.301 and 3.215 MUM for hCA I and II) and 5 (IC50 ;
      73.96 and 378.5 MUM for hCA I and II) compounds were found to cause inhibition on
      enzyme activities of hCA I and II.

PMID- 29327807
TI  - Uric acid is important, but there is something that matters even more: to deliver
      sacubitril/valsartan to eligible heart failure patients.

PMID- 29327809
TI  - The Prevalence of Cannabinoid Hyperemesis Syndrome Among Regular Marijuana
      Smokers in an Urban Public Hospital.
AB  - Epidemiological data, including prevalence, for cannabinoid hyperemesis syndrome
      (CHS) remain largely unknown. Without these data, clinicians often describe CHS
      as 'rare' or 'very rare' without supporting evidence. We seek to estimate the
      prevalence of CHS in a population of patients presenting to a socio-economically
      and racially diverse urban Emergency Department of a public hospital. This study
      consisted of a questionnaire administered to a convenience sample of patients
      presenting to the ED of the oldest public hospital in the United States. Trained
      Research Associates (RAs) administered the questionnaire to patients between the
      ages of 18-49 years who reported smoking marijuana at least 20 days per month.
      The survey included questions related to CHS symptoms (nausea and vomiting) and
      Likert scale rankings on eleven symptom relief methods, including 'hot showers'.
      Patients were classified as experiencing a phenomenon consistent with CHS if they
      reported smoking marijuana at least 20 days per month and also rated 'hot
      showers' as five or more on the ten-point symptom relief method Likert scale for
      nausea and vomiting. Among 2127 patients approached for participation, 155 met
      inclusion criteria as smoking 20 or more days per month. Among those surveyed,
      32.9% (95% CI, 25.5-40.3%) met our criteria for having experienced CHS. If this
      is extractable to the general population, approximately 2.75 million (2.13-3.38
      million) Americans may suffer annually from a phenomenon similar to CHS.

PMID- 29327808
TI  - The rocky road to personalized medicine in acute myeloid leukaemia.
AB  - Acute myeloid leukaemia (AML) is a malignant disorder of the myeloid blood
      lineage characterized by impaired differentiation and increased proliferation of
      hematopoietic precursor cells. Recent technological advances have led to an
      improved understanding of AML biology but also uncovered the enormous cytogenetic
      and molecular heterogeneity of the disease. Despite this heterogeneity, AML is
      mostly managed by a 'one-size-fits-all' approach consisting of intensive, highly
      toxic induction and consolidation chemotherapy. These treatment protocols have
      remained largely unchanged for the past several decades and only lead to a cure
      in approximately 30-35% of cases. The advent of targeted therapies in chronic
      myeloid leukaemia and other malignancies has sparked hope to improve patient
      outcome in AML. However, the implementation of targeted agents in AML therapy has
      been unexpectedly cumbersome and remains a difficult task due to a variety of
      disease- and patient-specific factors. In this review, we describe current
      standard and investigational therapeutic strategies with a focus on targeted
      agents and highlight potential tools that might facilitate the development of
      targeted therapies for this fatal disease. The classes of agents described in
      this review include constitutively activated signalling pathway inhibitors,
      surface receptor targets, epigenetic modifiers, drugs targeting the interaction
      of the hematopoietic progenitor cell with the stroma and drugs that target the
      apoptotic machinery. The clinical context and outcome with these agents will be
      examined to gain insight about their optimal utilization.

PMID- 29327810
TI  - Nebulized hypertonic saline in infants hospitalized with moderately severe
      bronchiolitis due to RSV infection: A multicenter randomized controlled trial.
AB  - INTRODUCTION: The efficacy of nebulized hypertonic saline (HS) therapy for
      shortening hospital length of stay (LOS) or improving bronchiolitic symptoms
      remains controversial. Most studies enrolled small numbers of subjects and did
      not consider the role of respiratory syncytial virus (RSV), the most common cause
      of acute bronchiolitis. Our aim was to evaluate the efficacy and safety of
      nebulized HS therapy for acute bronchiolitis due to RSV in moderately ill
      hospitalized infants. MATERIALS AND METHODS: This was an open-label, multicenter,
      randomized controlled trial comparing a nebulized HS treatment group with a
      normal saline (NS) group. The subjects, 128 infants with bronchiolitis due to
      RSV, were admitted to five hospitals in Tokyo, Japan. Three-percent HS or NS was
      administered via bronchodilator four times daily post-admission. The primary
      outcome was LOS, defined as the time until the patients fulfilled the discharge
      criteria, namely, absence of fever, no need for supplemental oxygen, and adequate
      feeding. Survival analysis was conducted in accordance with the intention-to
      treat principle. RESULTS: The baseline characteristics were similar between the
      two groups. There was no significant overall difference in LOS between the groups
      (4.81 +/- 2.14 days in HS vs 4.61 +/- 2.18 days in NS; P = 0.60). Survival
      analysis by log-rank test also showed no significance (P = 0.62). Multivariate
      adjustment did not significantly alter the results. The treatment was well
      tolerated, with no adverse effects attributable to the use of HS. CONCLUSIONS:
      Nebulized HS therapy did not significantly reduce LOS among infants with
      bronchiolitis due to RSV.

PMID- 29327811
TI  - An Aza resveratrol-chalcone derivative 6b protects mice against diabetic
      cardiomyopathy by alleviating inflammation and oxidative stress.
AB  - Inflammation and oxidative stress play a crucial role in the development of
      diabetic cardiomyopathy (DCM). We previously had synthesized an Aza resveratrol
      chalcone derivative 6b, of which effectively suppressing lipopolysaccharide (LPS)
      induced inflammatory response in macrophages. This study aimed to investigate the
      potential protective effect of 6b on DCM and underlying mechanism. In H9c2
      myocardial cells, 6b potently decreased high glucose (HG)-induced cell fibrosis,
      hypertrophy and apoptosis, alleviating inflammatory response and oxidant stress.
      In STZ-induced type 1 diabetic mice (STZ-DM1), orally administration with 6b for
      16 weeks significantly attenuated cardiac hypertrophy, apoptosis and fibrosis.
      The expression of inflammatory cytokines and oxidative stress biomarkers was also
      suppressed by 6b distinctly, without affecting blood glucose and body weight. The
      anti-inflammatory and antioxidative activities of 6b were mechanistic associated
      with nuclear factor-kappa B (NF-kappaB) nucleus entry blockage and Nrf2
      activation both in vitro and in vivo. The results indicated that 6b can be a
      promising cardioprotective agent in treatment of DCM via inhibiting inflammation
      and alleviating oxidative stress. This study also validated the important role of
      NF-kappaB and Nrf2 taken in the pathogenesis of DCM, which could be therapeutic
      targets for diabetic comorbidities.

PMID- 29327812
TI  - Hyper-acetylation contributes to the sensitivity of chemo-resistant prostate
      cancer cells to histone deacetylase inhibitor Trichostatin A.
AB  - Therapeutic agents are urgently needed for treating metastatic castration
      refractory prostate cancer (mCRPC) that is unresponsive to androgen deprivation
      and chemotherapy. Our screening assays demonstrated that chemotherapy-resistant
      prostate cancer (PCa) cells are more sensitive to HDAC inhibitors than paired
      sensitive PCa cells, as demonstrated by cell proliferation and apoptosis in vitro
      and in vivo. Kinetic study revealed that TSA-induced apoptosis was significantly
      dependent on enhanced transcription and protein synthesis in an early stage,
      which subsequently caused ER stress and apoptosis. ChIP analysis indicated that
      TSA increased H4K16 acetylation, promoting ER stress gene transcription. The
      changes in Ac-H4K16, ATF3 and ATF4 were also validated in TSA-treated animals.
      Further study revealed the higher enzyme activity of HDACs and an increase in
      acetylated proteins in resistant cells. The higher nucleocytoplasmic acetyl-CoA
      in resistant cells was responsible for elevated acetylation status of protein and
      a more vigorous growth state. These results strongly support the pre-clinical
      application of HDAC inhibitors for treating chemotherapy-resistant mCRPC.

PMID- 29327813
TI  - Computational Tools for the Identification and Interpretation of Sequence Motifs
      in Immunopeptidomes.
AB  - Recent advances in proteomics and mass-spectrometry have widely expanded the
      detectable peptide repertoire presented by major histocompatibility complex (MHC)
      molecules on the cell surface, collectively known as the immunopeptidome. Finely
      characterizing the immunopeptidome brings about important basic insights into the
      mechanisms of antigen presentation, but can also reveal promising targets for
      vaccine development and cancer immunotherapy. This report describes a number of
      practical and efficient approaches to analyze immunopeptidomics data, discussing
      the identification of meaningful sequence motifs in various scenarios and
      considering current limitations. Guidelines are provided for the filtering of
      false hits and contaminants, and to address the problem of motif deconvolution in
      cell lines expressing multiple MHC alleles, both for the MHC class I and class II
      systems. Finally, it is demonstrated how machine learning can be readily employed
      by non-expert users to generate accurate prediction models directly from mass
      spectrometry eluted ligand data sets.

PMID- 29327814
TI  - Systematic Evaluation of Protein Sequence Filtering Algorithms for Proteoform
      Identification Using Top-Down Mass Spectrometry.
AB  - Complex proteoforms contain various primary structural alterations resulting from
      variations in genes, RNA, and proteins. Top-down mass spectrometry is commonly
      used for analyzing complex proteoforms because it provides whole sequence
      information of the proteoforms. Proteoform identification by top-down mass
      spectral database search is a challenging computational problem because the types
      and/or locations of some alterations in target proteoforms are in general
      unknown. Although spectral alignment and mass graph alignment algorithms have
      been proposed for identifying proteoforms with unknown alterations, they are
      extremely slow to align millions of spectra against tens of thousands of protein
      sequences in high throughput proteome level analyses. Many software tools in this
      area combine efficient protein sequence filtering algorithms and spectral
      alignment algorithms to speed up database search. As a result, the performance of
      these tools heavily relies on the sensitivity and efficiency of their filtering
      algorithms. Here, we propose two efficient approximate spectrum-based filtering
      algorithms for proteoform identification. We evaluated the performances of the
      proposed algorithms and four existing ones on simulated and real top-down mass
      spectrometry data sets. Experiments showed that the proposed algorithms
      outperformed the existing ones for complex proteoform identification. In
      addition, combining the proposed filtering algorithms and mass graph alignment
      algorithms identified many proteoforms missed by ProSightPC in proteome-level
      proteoform analyses.

PMID- 29327815
TI  - No Impact of Pre-existing Cardiovascular Disease on Prescribing Patterns of
      Sulphonylureas in Denmark - A Registry-based Nationwide Study.
AB  - Uncertainty exists regarding cardiovascular (CV) safety of sulphonylureas (SUs)
      as reflected in package labels and treatment guidelines. This study evaluated
      clinical treatment practice for SUs by analysing prescription patterns for SUs
      relative to patient history of CV disease (CVD). Patients in Denmark initiating
      treatment with SU or other anti-hyperglycaemic drugs during 2006-12 were
      retrospectively identified using national health registries. Pre-existing
      (previous 12 years) overall CVD, coronary heart disease (CHD) and myocardial
      infarction (MI) were subsequently identified. Proportion of patients with pre
      existing CVD was compared between new users of SU and new users of other anti
      hyperglycaemic drugs. In total, 50,425 (42.2% females, mean +/- SD age 63.3 +/-
      13.5 years) and 190,438 (46.5% females, age 60.3 +/- 15.0 years) patients
      initiated treatment with SU or other anti-hyperglycaemic drugs, respectively,
      during 2006-12. The number of patients initiating SU treatment decreased by 63%
      during 2006-12. The proportion of patients with pre-existing CVD varied between
      46.9% and 49.8% among new SU users versus 39.9% and 44.8% among new users of
      other anti-hyperglycaemic drugs. Corresponding proportions for CHD (17.9-19.9%
      versus 15.4-16.9%) and MI (6.3-7.5% versus 5.8-6.2%) showed the same pattern.
      Excluding new gliclazide users (9.6% of all new SU users) from the SU definition
      did not alter the results. Despite a potentially increased CV risk associated
      with use of SUs, pre-existing CVD did not decrease clinicians' relative
      prescriptions of SUs.

PMID- 29327817
TI  - Ketonization of Proline Residues in the Peptide Chains of Actinomycins by a 4
      Oxoproline Synthase.
AB  - X-type actinomycins (Acms) contain 4-hydroxyproline (Acm X0 ) or 4-oxoproline
      (Acm X2 ) in their beta-pentapeptide lactone rings, whereas their alpha ring
      contains proline. We demonstrate that these Acms are formed through asymmetric
      condensation of Acm half molecules (Acm halves) containing proline with 4
      hydroxyproline- or 4-oxoproline-containing Acm halves. In turn, we show-using an
      artificial Acm half analogue (PPL 1) with proline in its peptide chain-their
      conversion into the 4-hydroxyproline- and 4-oxoproline-containing Acm halves, PPL
      0 and PPL 2, in mycelial suspensions of Streptomyces antibioticus. Two
      responsible genes of the Acm X biosynthetic gene cluster of S. antibioticus,
      saacmM and saacmN, encoding a cytochrome P450 monooxygenase (Cyp) and a
      ferredoxin were identified. After coexpression in Escherichia coli, their gene
      products converted PPL 1 into PPL 0 and PPL 2 in vivo as well as in situ in
      permeabilized cell of the transformed E. coli strain in conjunction with the host
      encoded ferredoxin reductase in a NADH (NADPH)-dependent manner. saAcmM has high
      sequence similarity to the Cyp107Z (Ema) family of Cyps, which can convert
      avermectin B1 into its keto derivative, 4''-oxoavermectin B1. Determination of
      the structure of saAcmM reveals high similarity to the Ema structure but with
      significant differences in residues decorating their active sites, which defines
      saAcmM and its orthologues as a distinct new family of peptidylprolineketonizing
      Cyp.

PMID- 29327816
TI  - Brain-Cortex Microglia-Derived Exosomes: Nanoparticles for Glioma Therapy.
AB  - The function and integrity of the nervous system require interactive exchanges
      among neurons and glial cells. Exosomes and other extracellular vesicles (EVs)
      are emerging as a key mediator of intercellular communication, capable of
      transferring nucleic acids, proteins and lipids influencing numerous functional
      and pathological aspects of both donor and recipient cells. The immune response
      mediated by microglia-derived exosomes is most prominently involved in the spread
      of neuroinflammation, neurodegenerative disorders, and brain cancer. Therefore,
      in the present study we describe a reproducible and highly efficient method for
      yielding purified primary microglia cells, followed by exosome isolation and
      their characterization. An in vitro biological assay demonstrates that microglia
      derived exosomes tested on a 3D spheroid glioma culture were able to inhibit
      tumor invasion in time course. These results evidence that brain microglia
      derived exosomes could be used as nanotherapeutic agents against glioma cells.

PMID- 29327818
TI  - Cyclosporine for severe steroid-refractory ulcerative colitis: commenting the
      comment.

PMID- 29327819
TI  - Helicobacter pylori infection in Africa: 2018 literature update.
AB  - Helicobacter pylori (H. pylori) relationship with humans is believed to have
      originated in Africa and three African H. pylori populations have been
      identified: hpAfrica1, hpAfrica2 and hpNEAfrica. Actually, H. pylori infection is
      a ubiquitous infection in developing countries, particularly Africa. In this
      continent, the prevalence of H. pylori is higher and the bacterium is acquired at
      an early age compared to developed countries. In fact, while it affects over 50%
      of humans in developed countries its prevalence reaches 80% or more among adults
      in Africa. This paper reviews works in literatures, including epidemiology,
      virulence genes, gastric pathology and antimicrobial treatment and resistance of
      H. pylori in Africa.

PMID- 29327820
TI  - Gastroenterology today: between certainties and news.
AB  - This special article reports on two crucial issues discussed during a meeting.
      The first was the updated management of Helicobacter pylori (H. pylori)
      infection. This was approached taking into account the recent European
      Guidelines, with a focus on novelties in treatment. In particular, considering
      the increasing H. pylori antibiotic resistance to clarithromycin, in countries
      with a high clarithromycin resistance rate, the bismuth-containing quadruple
      therapies should be preferred. The new formulation, with bismuth, metronidazole,
      and tetracycline contained in a single capsule (three-in-one), has shown exciting
      results both in naive and in non-responder patients. Levofloxacin- and rifabutin
      containing triple therapies should be proposed to patients who experienced H.
      pylori treatment failures. Another key message on H. pylori management was that,
      after one or more failures, standard antimicrobial susceptibility testing should
      be considered before prescribing a further treatment. The second issue concerned
      the novelties on dysbiosis of intestinal microbiota and its clinical
      consequences. Among the latter, the focus was on both constipation-predominant
      irritable bowel syndrome (IBS-C) and microscopic colitis. Since the number of
      microorganisms inhabiting the gastrointestinal (GI) tract is estimated to be
      about 10 times higher than that of human cells, it is not surprising to foresee
      the clinical consequences of dysbiosis. However, to date the role of dysbiosis in
      IBS-C and in microscopic colitis is poorly known and major efforts are needed to
      understand if manipulating microbiota could improve the treatment of these and
      other diseases both within and outside the GI tract. At a meeting held in Turin,
      Italy, on May 27, 2017 two crucial issues of modern gastroenterology were
      discussed: the updated management of Helicobacter pylori (H. pylori) infection
      and the novelties regarding the dysbiosis of intestinal microbiota and its
      clinical consequences. Among the latter, a focus was made on both constipation
      predominant irritable bowel syndrome (IBS-C) and microscopic colitis. In this
      special article we report the most recent salient advances discussed during this
      meeting.

PMID- 29327821
TI  - Chronic kidney disease in patients with chronic hepatitis C virus infection.
AB  - Hepatitis C virus (HCV) infection affects many organs in the body, including the
      liver, kidneys, skin, joints and others. Although the hepatic manifestation of
      HCV has been widely studied, the extrahepatic manifestations of HCV have not been
      fully appreciated. Studies have shown that patients with HCV have a higher risk
      of chronic kidney disease and end-stage renal disease, as well as poorer outcomes
      after kidney transplantation. Given these findings, it is important to screen HCV
      patients for presence of renal impairment in a timely manner. Current guidelines
      recommend screening for kidney disease at the time of HCV diagnosis, along with
      annual urinalysis and creatinine checks. It is important to note that chronic HCV
      infection has been associated with a number of renal disorders, including
      cryoglobulinemic glomerulonephritis, membranoproliferative glomerulonephritis,
      membranous nephropathy, focal segmental glomerulosclerosis, IgA nephropathy,
      fibrillary and immunotactoid glomerulopathies, and hepatorenal syndrome. Of
      these, while HRS can be reversible post-transplantation, cryoglobulinemic
      glomerulonephritis is common and is primarily caused by mixed cryoglobulinemia.
      These patients may be asymptomatic or may present with hematuria, proteinuria,
      nephrotic syndrome, or impaired renal function only detected by laboratory data.
      In this review, we will provide an up-to-date assessment of these renal
      complications in patients with HCV infection.

PMID- 29327822
TI  - Efficacy and safety of long-term entecavir therapy in a European population.
AB  - BACKGROUND: Therapy in chronic hepatitis B (chronic hepatitis B) patients aims at
      improving their survival by preventing disease progression to cirrhosis and its
      complications. Entecavir (ETV) is currently a first line therapeutic agent
      recommended for the treatment of CHB. Our aim was to evaluate the long term
      outcome of a cohort of CHB patients treated with ETV. METHODS: Thirty-four
      patients treated with ETV for at least 6 months were included in this study. The
      virologic response was determined by the dosage of serum HBV-DNA, HBsAg, HBeAg,
      anti-HBs and anti-HBe antibodies. Death, acute pancreatitis, lactic acidosis and
      kidney function impairment were considered as major adverse events. RESULTS: The
      median period of treatment was 55 months (range 15-81). Thirty-three (97%)
      patients responded to the therapy after a mean time of 14.7 weeks (4-60); of
      these, 29 (85.3%) maintained the HBV-DNA negativity in serum, while 4 patients
      (11.8%) had a breakthrough. The remaining patient did not respond. Seroconversion
      to anti-HBs and anti-HBe was not observed, although 2 patients lost the e and the
      s antigen, respectively. Baseline alanine aminostransferase (ALT) levels in serum
      were altered in 18 patients (52.9%), and returned to normal levels during the
      follow-up, with a reduction of 87.7 IU/L (P<0.0001). A case (3.4%) of
      hepatocellular carcinoma was observed after 24 months. No major adverse events
      were recorded. CONCLUSIONS: ETV is effective in suppressing viral replication as
      well as in normalizing serum ALT levels, without anti-HBs seroconversion.
      Finally, ETV is a safe drug, substantially free of major side effects.

PMID- 29327823
TI  - A previous hamstring injury affects kicking mechanics in soccer players.
AB  - BACKGROUND: Although the kicking skill is influenced by limb dominance and sex,
      how a previous hamstring injury affects kicking has not been studied in detail.
      Thus, the objective of this study was to evaluate the effect of sex and limb
      dominance on kicking in limbs with and without a previous hamstring injury.
      METHODS: 45 professional players (males: n=19, previously injured players=4,
      age=21.16 +/- 2.00 years; females: n=19, previously injured players=10, age=22.15
      +/- 4.50 years) performed 5 kicks each with their preferred and non-preferred
      limb at a target 7m away, which were recorded with a three-dimensional motion
      capture system. Kinematic and kinetic variables were extracted for the backswing,
      leg cocking, leg acceleration and follow through phases. RESULTS: A shorter
      backswing (20.20 +/- 3.49% vs 25.64 +/- 4.57%), and differences in knee flexion
      angle (58 +/- 10o vs 72 +/- 14o) and hip flexion velocity (8 +/- 0rad/s vs 10 +/-
      2rad/s) were observed in previously injured, non-preferred limb kicks for
      females. A lower peak hip linear velocity (3.50 +/- 0.84m/s vs 4.10 +/- 0.45m/s)
      was observed in previously injured, preferred limb kicks of females. These
      differences occurred in the backswing and leg-cocking phases where the hamstring
      muscles were the most active. A variation in the functioning of the hamstring
      muscles and that of the gluteus maximus and iliopsoas in the case of a previous
      injury could account for the differences observed in the kicking pattern.
      CONCLUSIONS: Therefore, the effects of a previous hamstring injury must be
      considered while designing rehabilitation programs to re-educate kicking
      movement.

PMID- 29327824
TI  - Are there bilateral isokinetic shoulder rotator differences in basketball male
      players?
AB  - BACKGROUND: The internal (IR) and external (ER) rotator shoulder strength are
      often assess in the upper limb sports to prevent a risk of injuries. The purpose
      of this comparative study was to measure the agonist/antagonist balance of
      shoulder strength and to determine whether significant differences exist between
      the dominant and nondominant sides in basketball players compared to a control
      groups. METHODS: During the championship, 23 elite male-basketball players (BB)
      and 23 healthy males (CG) were tested bilaterally on a Cybex Norm isokinetic
      dynamometer in a seated position with 45 degrees  shoulder abduction in the
      scapular plane at 60 degrees .s-1 and 180 degrees .s-1 in concentric (CON) and 60
      degrees .s-1 in eccentric (ECC) modes. RESULTS: No significant differences were
      found for normalized values to body weight (N.m/kg-1) between the both groups and
      ER/IR, ECC/CON and functional deceleration ratios were similar. BB have a
      bilateral difference with higher ER of the dominant side comparatively to the
      opposite (P<0.05). CONCLUSIONS: Unlike other sports that increase the performance
      of IR dominant side, the basketball player isokinetic profile could indicate a
      strengthening in the external rotators of the dominant side. This bilateral
      difference could be explained by the repetition of the specific movements in the
      ball control but this was not large enough for the ER/IR ratios to be
      significantly different with CG. The ratios analysis does not report an imbalance
      associated with a high risk of shoulder injuries.

PMID- 29327825
TI  - The sagittal spinal alignment in young swimmers and glide performance: the
      importance of lumbar lordosis.

PMID- 29327826
TI  - Correlation between hypermobility score and injury rate in artistic gymnastics.
AB  - BACKGROUND: Generalized Joint Hypermobility (GJH) is suggested as a contributing
      factor for injuries in young athletes and adults. It is presumed that GJH causes
      decreased joint stability, thereby increasing the risk of joint and soft tissue
      injuries during sports activities. The aim of this study was to determine the
      correlation between the hypermobility rate (using the Beighton's modification of
      the Carter-Wilkinson criteria of hypermobility) in gymnasts and injury rate,
      during the period of one year. METHODS: This study observed 24 artistic gymnasts
      (11-26 years old), members of Qatar National Team in artistic gymnastics. We
      examined the Beighton joint hypermobility screen and a seasonal injury survey.
      The gymnasts characteristics (age, gender) and gymnastics characteristics
      (training per day and number of years in training artistic gymnastics) and its'
      relations to injury rate were also included. RESULTS: The most common injury was
      the lower back pain injury, followed by knee, shoulder, hip and ankle injuries.
      We found strong correlation of number of years gymnastics training and injury
      rate (p<0.001). There is no significant correlation in the numbers of hours
      training during one week and hypermobility score to numbers of injuries (p>0.05).
      CONCLUSIONS: According to this study there is no correlation between GJH rate and
      injury rate in artistic gymnasts in Qatar. Total training period in gymnastics
      have greater contribution in injury rate.

PMID- 29327827
TI  - Differences in 100-m sprint performance and skeletal muscle mass between elite
      male and female sprinters.
AB  - BACKGROUND: The sex difference in 100-m sprint performance between the world's
      best athletes is approximately 10%. We hypothesized that skeletal muscle mass
      (SM) relative to body mass may be a major factor contributing to this difference.
      The aim of this study was to examine the sex difference in absolute and relative
      SM and sprint performance in male and female sprinters. METHODS: We analyzed the
      SM of male (n=37) and female (n=26) 100-m sprinters; the sample was divided into
      two subgroups within each sex according to personal best 100-m time: 10.00- 10.90
      s (M10; n=22) and 11.00-11.70 s (M11; n=15) for males and 11.00-11.90 s (F11,
      n=14) and 12.00-13.50 s (F12, n=12) for females. SM was estimated from ultrasound
      measured muscle thickness (MT) using prediction equations. RESULTS: There was an
      approximate 10% difference in 100-m sprint time between sexes, whereas absolute
      and relative values of SM for female sprinters were 70-71% and 79-84% of the male
      sprinters, respectively. No differences were observed within each male/female
      subgroup for fat-free mass, absolute and relative SM, excepting that leg SM index
      of M10 was higher than M11. The 100-m time was not different (0.27 s, p=0.051)
      between M11 and F11 subgroups, but absolute and relative values of SM and MT were
      higher and percent body fat was lower in the M11 than in the F11 subgroup.
      CONCLUSIONS: Our results suggest that differences in muscle mass may not play a
      large role in determining successful performance in elite male and female
      sprinters.

PMID- 29327828
TI  - The acute effects of stretching with vibration on dynamic flexibility in young
      female gymnasts.
AB  - BACKGROUND: While stretching with vibration has been shown to improve static
      flexibility; the effect of stretching with vibration on dynamic flexibility is
      not well known. The purpose of this study was to examine the effectiveness of
      stretching with vibration on acute dynamic flexibility and jump height in novice
      and advanced competitive female gymnasts during a split jump. METHODS: Female
      gymnast (n=27, age: 11.5 +/- 1.7 years, Junior Olympic levels 5-10) participated
      in this cross-over study. Dynamic flexibility during gymnastic split jumps were
      video recorded and analyzed with Dartfish software. All participants completed
      both randomized stretching protocols with either the vibration platform turned on
      (VIB) (frequency of 30 Hz and 2 mm amplitude) or off (NoVIB) separated by 48 h.
      Participants performed 4 sets of three stretches on the vibration platform. Each
      stretch was held for 30 s with 5 s rest for a total of 7 min of stretch. RESULTS:
      Split jump flexibility decreased significantly from pre to post measurement in
      both VIB (-5.8 degrees +/-5.9 degrees ) (p<0.001) and NoVIB (-2.6 degrees +/-6.1
      degrees ) (p=0.041) conditions (adjusted for gymnast level). This effect was
      greatest in lower skill level gymnasts (p=0.003), while the highest skill level
      gymnasts showed no significant decrease in the split jump (p=0.105). Jump height
      was not significantly different between conditions (p=0.892) or within groups
      (p=0.880). CONCLUSIONS: An acute session of static stretching with or without
      vibration immediately before performance does not alter jump height. Stretching
      with vibration immediately prior to gymnastics competition decreases split jump
      flexibility in lower level gymnasts more than upper level gymnasts.

PMID- 29327862
TI  - Endoscopic fenestration of a posterior fossa arachnoid cyst to treat a Chiari
      like headache.

PMID- 29327861
TI  - Prognostic factors in intrauterine insemination cycles.
AB  - OBJECTIVE: This study aimed to evaluate the clinical pregnancy rate of
      intrauterine insemination cycles in relation to patient age, cause of
      infertility, ovulation induction method, number of mature follicles and sperm
      with progressive motility. METHODS: This retrospective observational study
      included 237 intrauterine insemination cycles performed from 2011 to 2015 at the
      Assisted Reproduction Service of the Hospital das Clinicas of the Ribeirao Preto
      Medical School, University of Sao Paulo. Student's t-test was used to compare
      quantitative variables and the chi-square test was used to compare qualitative
      variables. RESULTS: Patient age was inversely and significantly correlated with
      pregnancy rates (p=0.001) (Pregnant women = 32.56+/-5.64 years, non-pregnant
      women = 36.64+/-5.03 years). Cause of infertility, ovulation induction method,
      number of mature follicles and sperm with progressive motility were not
      associated with pregnancy rates. The overall clinical pregnancy rate was 7.59%.
      In the subgroup of patients (n=102 cycles) considered ideal for intrauterine
      insemination (age <=35 years, unexplained infertility, ovarian factor infertility
      or minimal endometriosis, and a partner with sperm count >=2.5 * 106 retrieved on
      the day of insemination) the pregnancy rate was 12.74%. CONCLUSION: In the
      studied group, female patient age was the only variable significantly correlated
      with intrauterine insemination success rates.

PMID- 29327863
TI  - Endoscopic endonasal transpterygoid approach to petrous pathologies: technique,
      limitations and alternative approaches.
AB  - The endoscopic endonasal transpterygoid approach is a versatile technique,
      providing direct access to the petrous apex through an anterior surgical
      corridor. In this review we detail the transpterygoid approach to the petrous
      apex and highlight its relative indications. Although this approach is a useful
      strategy for many lesions of the petrous apex, disease extension into lateral,
      superior, or posterior compartments may limit extent of resection afforded by an
      anterior approach alone. Based on these considerations, a disease compartment
      specific strategy is discussed. The limitations of the transpterygoid approach
      and indications for lateral and postero-lateral approaches to petrous pathology
      are reviewed.

PMID- 29327864
TI  - Limits of endoscopic endonasal approach for cranio-vertebral junction tumors.
AB  - BACKGROUND: The endoscopic endonasal approach has been recently proposed for
      cranio-vertebral junction lesions. The more common indication for this sagittal
      extension of the endonasal route is represented by odontoidectomy for irreducible
      ventral brainstem compression due to congenital or degenerative conditions.
      However, in an increasing number of studies its adoption for tumors involving the
      cranio-cervical junction has been reported. The aim of this study is to consider
      retrospectively our surgical series, focusing on the advantages and limits of
      this approach. METHODS: Each consecutive case of tumor involving the cranio
      vertebral junction since 2007 to 2017 treated through an endoscopic endonasal
      approach has been included. All patients undergone preoperative neurological
      examination and neuroimaging (magnetic resonance imaging [MRI] and computed
      tomography angiography). These examinations were repeated after 3 months and then
      annually. Complementary treatments, recurrence rate and clinical status at mean
      follow-up of 18+/-7.3 months were considered. RESULTS: Seven patients have been
      included in this study, mean age was of 47+/-17 years; male-to-female ratio was
      of 3:4. Series is composed by 6 chordomas and one foramen magnum meningioma. One
      patient had been already posteriorly stabilized for cranio-vertebral instability.
      Gross tumor removal was achieved in two cases, in the others a subtotal removal
      was demonstrated at postoperative MRI. One patient presented a transitory
      worsening of CN XII palsy, resolved within 3 months. For preoperative dysphagia
      and inhalation pneumonia, one case undergone tracheostomy and was fed with oro
      gastric tube for 10 days. Three patients died for chordoma progression and at
      follow-up one presented a local recurrence. CONCLUSIONS: Despite our experience
      is preliminary, the endoscopic endonasal approach has resulted safe for cranio
      cervical junction tumor with a reduced number of complications. It can give a
      straight and direct trajectory to this deep region. We suggest that lateral
      extension of the tumor beyond the plane of cranial nerves is a limit for this
      approach, as well as an inferior expansion caudal to C1. Larger series and longer
      follow-up are required to assess the proper indications of this approach.

PMID- 29327892
TI  - Measurement of the accuracy of dental working casts using a coordinate measuring
      machine.
AB  - Background/Aim: Dental impressions present a negative imprint of intraoral
      tissues of a patient which is, by pouring in gypsum, transferred extraorally on
      the working cast. Casting an accurate and precise working cast presents the first
      and very important step, since each of the following stages contributes to the
      overall error of the production process, which can lead to inadequately fitting
      dental restorations. The aim of this study was to promote and test a new model
      and technique for in vitro evaluation of the dental impression accuracy, as well
      as to asses the dimensional stability of impression material depending on the
      material bulk, and its effect on the accuracy of working casts. Methods:
      Impressions were made by the monophasic technique using the experimental master
      model. Custom trays with spacing of 1, 2 and 3 mm were constructed by rapid
      prototyping. The overall of 10 impressions were made with each custom tray.
      Working casts were made with gypsum type IV. Measurement of working casts was
      done 24 h later using a co-ordinate measuring machine. Results: The obtained
      results show that the working casts of all the three custom trays were in most
      cases significantly different in the transversal and sagittal planes in relation
      to the master model. The height of abutments was mainly unaffected. The degree of
      convergence showed certain significance in all the three custom trays, most
      pronounced in the tray with 3 mm spacing. Conclusion: The impression material
      bulk of 1-3 mm could provide accurate working casts when using the monophasic
      impression technique. The increase of the distance between abutment teeth
      influences the accuracy of working casts depending on the material bulk.
      [Projekat Ministarstva nauke Republike Srbije, br. TR 35020: Research and
      development of modelling methods and approaches in manufacturing of dental
      recoveries with the application of modern technologies and computer aided
      systems]

PMID- 29327893
TI  - Heart failure in grown-up congenital heart disease.
AB  - The increasing survival to adulthood of patients with congenital heart disease
      (CHD) has changed the epidemiology of adult CHD (ACHD) patients and has led to an
      increment in hospitalization rates due to heart failure (HF). ACHD patients
      hospitalized for HF have a five-fold higher risk of death than those compensated.
      HF occurs predominantly in patients with tetralogy of Fallot, single ventricles,
      and after the Mustard operation for transposition of the great arteries.
      Diagnostic strategies applied in acquired HF patients are usually used to
      evaluate ACHD patients, but sometimes this can postpone the identification of HF
      that can become manifest with unusual and peculiar signs or symptoms. In the same
      way, therapeutic management resembles the acquired HF one, even if no large
      randomized clinical trials have been conducted in ACHD patients. Therefore, a
      close monitoring in dedicated units is mandatory in order to identify in time HF
      manifestations and manage them adequately.

PMID- 29327894
TI  - Cell therapy for heart disease: current status and future directions.
AB  - Treatment of ischemic heart disease has evolved considerably over time, seeing a
      technological impetus in recent times. Prompt diagnosis and progressively earlier
      reperfusion of the infarct artery have become the cornerstone of the early
      myocardial ischemia management. However, treatment of post-infarction sequelae
      resulting from ischemic damage sustained within the myocardium remains a
      considerable challenge. In this setting, stem cell therapy has emerged as an
      exciting regenerative modality with a promise to arrest or even reverse the
      pathological myocardial remodeling. Multiple preclinical and clinical studies
      have thereafter reported use of various types of stem cells delivered through
      varying routes. While most of these studies reported positive results, some
      appropriate concerns were raised in others. This has resulted in considerable
      uncertainty regarding cell therapy and an inability to formulate therapeutic
      recommendations. Though there has been a considerable improvement in our
      understanding of stem cell properties, there is a need to identify specific
      mechanisms of actions in order to maximize the benefits of stem cell therapy in
      ischemic heart disease. With this review, we attempt to highlight some of the
      salient features of stem cell research, focusing on understanding the predominant
      types of stem cells, proposed mechanisms of action, routes of administration, and
      application of this exciting and innovative regenerative therapy offered by stem
      cells.

PMID- 29327895
TI  - Antimicrobial susceptibility and beta-lactamase production in Bacillus cereus
      isolates from stool of patients, food and environment samples.
AB  - Background/Aim: Bacillus cereus (B. cereus) usually ingested by food can cause
      two types of diseases: vomiting due to the presence of emetic toxin and diarrheal
      syndrome, due to the presence of diarrheal toxins. Systemic manifestations can
      also occur. The severe forms of disease demand antibiotic treatmant. The aim of
      this study was to determine the differences in antibiotic susceptibility and beta
      lactamase activity of B. cereus isolates from stools of humans, food and
      environment. Methods: Identification of B. cereus was performed with selective
      medium, classical biochemical test and polymerase chain reaction (PCR) with
      primers specific for bal gene. Thirty isolates from each group were analysed for
      antibiotic susceptibility using the disk-diffusion assay. Production of beta
      lactamase was determined by cefinase test, and double-disc method. Results: All
      strains identified as B. cereus using classical biochemical test, yielded 533 bp
      fragment with PCR. Isolates from all the three groups were susceptible to
      imipenem, vancomycin, and erythromycin. All isolates were susceptible to
      ciprofloxacin but one from the environment. A statistically significant
      difference between the groups was confirmed to tetracycline and trimethoprim
      sulphamethoxazole sensitivity. A total of 28/30 (93.33%) samples from the foods
      and 25/30 (83.33%) samples from environment were approved sensitive to
      tetracycline, while 10/30 (33.33%) isolates from stools were sensitive. Opposite
      to this result, high susceptibility to trimethoprim-sulphamethoxazole was shown
      in samples from stools (100%), while isolates from foods (63.33%) and from
      environment (70%) had low susceptibility. All samples produced beta-lactamases.
      Conclusion: The strains of B. cereus from all the three groups showed high rate
      of sensitivity to most tested antibiotics, except to tetracycline in samples from
      human stool and to trimethoprim-sulphamethoxazole in samples from food and
      environment. The production of beta-lactamases was confirmed in all the strains.

PMID- 29327896
TI  - Obesity and metabolic syndrome as risk factors for the development of non
      alcoholic fatty liver disease as diagnosed by ultrasound.
AB  - Introduction/Aim: Non-alcoholic fatty liver disease (NAFLD) is a chronic liver
      disease of a broad histological spectrum, characterized by the accumulation of
      triglycerides in more than 5% of hepatocytes in the absence of consuming alcohol
      in quantities harmful to the liver. The aim of our study was to determine the
      importance of anthropometric and laboratory parameters as well as metabolic
      syndrome (MS) for the diagnosis of NAFLD and to estimate their influence on the
      degree of liver steatosis as evaluated by ultrasound (US). Methods: The study
      included 86 participants, 55 of whom had fatty liver diagnosed by ultrasound and
      they comprised the study group. The control group consisted of 31 control
      subjects. During the course of hospitalization at the Clinic of Gastroenterology
      and Hepatology, Clinical Centre Nis, the patients had their anamnesis taken, and
      anthropometric measurements as well as biochemical blood analyses and abdominal
      ultrasound were performed. Results: The patients with NAFLD had statistically
      higher values of body mass index (BMI), waist circumference (WC), systolic (SBP)
      and diastolic blood pressure (DBP), levels of alanin and aspartate
      aminotransferase (ALT, AST), gamma-glutamyl transpeptidase (GGT) (p<0.001), low
      density lipoprotein cholesterole (LDL), total bilirubin (TBIL) (p<0.05), total
      cholesterol (p<0.01), triglycerides (TGL), urates, C-reactive protein (CRP),
      ferritin, fibrinogenes, fasting blood glucose (FBG), insulin and Homeostasis
      Model Assessment (HOMA-IR) (p<0.001), whereas the levels of high-density
      lipoprotein cholesterol (HDL) were higher in the control group (p<0.05). In the
      NAFLD group, there were statistically significantly more patients with
      hypertension (72.73% vs. 12.90%, p<0.001) and type 2 diabetes mellitus (DM)
      (47.27%). Metabolic syndrome was determined in 48 (87.27%) patients of the study
      group. An equal number of patients, 16 of them (29.09%), had 3, 4 and 5
      components of MS. In the NAFLD group there were 17 overweight (30.91%) (BMI from
      25 kg/m2 to 29.9 kg/m2) and 38 (69.09%) obese patients. (BMI >= 30.0 kg/m2). The
      largest number of patients in the obesity group, 22 (40.00%) of them, had the
      first degree obesity (BMI from 30 kg/m2 to 34.99 kg/m2). The largest number of
      the NAFLD group patients - 23 (41.82%), had an ultrasound finding of grade 3
      fatty liver, 20 patients (36.36%) had grade 2 and 12 (21.82%) grade 1 fatty
      liver. Kruskal-Wallis test and ANOVA analysis showed statistically significant
      differences between groups with different US grade for insulin, LDL-cholesterol,
      WC, BMI (p<0.05), as well as HOMA-IR and body weight (BW) (p<0.01). Metabolic
      syndrome was statistically more present in patients with US finding grades 2 and
      3 (p<0.01) in relation to grade 1 US finding, as well as obesity, hypertension
      and DM type 2 (p<0.05). Conclusion: The results of our study have confirmed that
      a high percentage of patients with high risk factors (DM, MS, dyslipidemia,
      hypertension) have NAFLD.

PMID- 29327897
TI  - Peripheral arterial occlusive disease and perioperative risk.
AB  - Surgical procedures represent a risk for different complications which may appear
      during the perioperative period. Cardiac ischemic events and vascular
      complications are the most important causes of increased morbidity and mortality
      and they are much more frequent in patients with manifest cardiovascular disease.
      This is particularly seen in patients with peripheral arterial occlusive disease
      (PAD), which represents advanced atherosclerosis frequently accompanied by the
      presence of coronary artery disease. Therefore, patients with PAD need careful
      preoperative examination, including estimation of functional capacity and the
      presence of other co-existing atherosclerotic diseases. The perioperative risk of
      cardiac complications should be calculated by Apgar score. In patients with
      unstable coronary syndrome myocardial revascularization should be performed
      before vascular procedures, whereas in other coronary patients pharmacotherapy
      should be intensified. The latter includes beta-adrenergic receptor blockers,
      statin therapy, which significantly improves postoperative outcome and
      antiplatelet drugs, which do not significantly increase major bleeding
      complications but significantly reduce cardiovascular thromboembolic events.
      Postoperative strategy for prevention of complications should be focused
      particularly on identification of myocardial infarction which is frequently
      asymptomatic. Therefore, serial postoperative measurements of troponin levels
      allow close monitoring of postoperative myocardial damage and help to implement
      strategic choices for the treatment of postoperative adverse cardiac events.

PMID- 29327898
TI  - Association of different electrocardiographic patterns with shock index, right
      ventricle systolic pressure and diameter, and embolic burden score in pulmonary
      embolism.
AB  - Background/Aim: Some electrocardiographic (ECG) patterns are characteristic for
      pulmonary embolism but exact meaning of the different ECG signs are not well
      known. The aim of this study was to determine the association between four common
      ECG signs in pulmonary embolism [complete or incomplete right bundle branch block
      (RBBB), S-waves in the aVL lead, S1Q3T3 sign and negative T-waves in the
      precordial leads] with shock index (SI), right ventricle diastolic diameter
      (RVDD) and peak systolic pressure (RVSP) and embolic burden score (EBS). Methods:
      The presence of complete or incomplete RBBB, S waves in aVL lead, S1Q3T3 sign and
      negative T-waves in the precordial leads were determined at admission ECG in 130
      consecutive patients admitted to the intensive care unit of a single tertiary
      medical center in a 5-year period. Echocardiography examination with measurement
      of RVDD and RVSP, multidetector computed tomography pulmonary angiography (MDCT
      PA) with the calculation of EBS and SI was determined during the admission
      process. Multivariable regression models were calculated with ECG parameters as
      independent variables and the mentioned ultrasound, MDCT-PA parameters and SI as
      dependent variables. Results: The presence of S-waves in the aVL was the only
      independent predictor of RVDD (F = 39.430, p < 0.001; adjusted R2 = 0.231) and
      systolic peak right ventricle pressure (F = 29.903, p < 0.001; adjusted R2 =
      0.185). Negative T-waves in precordial leads were the only independent predictor
      for EBS (F = 24.177, p < 0.001; R2 = 0.160). Complete or incomplete RBBB was the
      independent predictor of SI (F = 20.980, p < 0.001; adjusted R2 = 0.134).
      Conclusion: In patients with pulmonary embolism different ECG patterns at
      admission correlate with different clinical, ultrasound and MDCT-PA parameters.
      RBBB is associated with shock, Swave in the aVL is associated with right
      ventricle pressure and negative T-waves with the thrombus burden in the pulmonary
      tree.

PMID- 29327910
TI  - Local recurrence in patients treated for rectal cancer using total mesorectal
      excision or transection of mesorectum.
AB  - Background/Aim: Rectal cancer is a major health problem throughout the world,
      despite the great progress in the treatment and control of the disease. The aim
      of this study was to determine the effect of mesorectal excision type on local
      recurrence in patients operated on for rectal cancer within a 3- year period.
      Methods: The clinical retrospective study was conducted at the Clinic for General
      Surgery at the Clinical Center in Nis, Serbia, and included 225 patients with
      rectal cancer. Postoperatively, the patients were observed 36 months. Total
      mesorectal excision (TME) method was used in 129 (57.33%) patients, and partial
      mesorectal excision (PME) in 96 (42.66%). There were 145 (64.44%) man and 80
      (35.55%) women, average age 66.8 years. Results: In 58 (25.77%) of the patients
      cancer was localized in the proximal third of the rectum, in 99 (44%) in the
      medium third, in 68 (30.22%) it was 8 cm of the anocutaneous line. In 167
      (74.22%) patients rectal cancer was in T3 stadium. TME was performed in all the
      patients with cancer in the distal third of the rectum and in 61.61% of the
      patients with cancer in the medium third of the rectum. PME was performed in all
      the patients with localized cancer in the proximal third and in 38.38% of the
      patients with cancer in the medium third of the rectum. Local recurrence occurred
      in 20 (8.88%) patients, 12 (9.30%) in the TME group and 8 (8.33%) in the PME
      group, which was not a statistically significant difference. In 75% of the cases,
      relapse occurred in the patients in T3 stage. Relapse occurred in 55% of the
      cases in the second year after the surgery. The median survival of all the
      patients amounted to 35 months. The total mortality of all respondents in a 3
      year period amounted to 5.3%. Conclusion: There were no statistically significant
      differences in the incidence of local recurrence and survival among patients who
      underwent TME and those underwent PME. The type of mesorectal excision does not
      affect the incidence of local recurrence in node-negative disease stages.

PMID- 29327911
TI  - Enhanced Charge Separation Efficiency Accelerates Hydrogen Evolution from Water
      of Carbon Nitride and 3,4,9,10-Perylene-tetracarboxylic Dianhydride Composite
      Photocatalyst.
AB  - The catalytic ability of graphitic carbon nitride is greatly affected by its
      intrinsic electronic properties. Although combination with chromophore has been
      demonstrated to be one of the promising approaches to improve the catalytic
      performance of carbon nitride, it is imperative to understand the key factors
      governing the whole process. Here, we report a composite photocatalyst CN-P by
      embedding perylene unit into the matrix of carbon nitride. The composite
      photocatalyst could catalyze hydrogen evolution with a high rate of 17.7 mmol h-1
      g-1, which is 2.8 times faster than pure carbon nitride. The apparent quantum
      efficiency is high up to be 5.8% at 450 nm. Detailed studies reveal that the
      light absorption ability and charge separation efficiency are greatly enhanced in
      the synthesized catalyst. These are the key factors for the improved hydrogen
      evolution ability of CN-P than that of pure carbon nitride.

PMID- 29327912
TI  - Reliable Manipulation of Gas Bubble Size on Superaerophilic Cones in Aqueous
      Media.
AB  - Gas bubbles in aqueous media are ubiquitous in a broad range of applications. In
      most cases, the size of the bubbles must be manipulated precisely. However, it is
      very difficult to control the size of gas bubbles. The size of gas bubbles is
      affected by many factors both during and after the generation process. Thus,
      precise manipulation of gas bubble size still remains a great challenge. The
      ratchet and conical hairs of the Chinese brush enable it to realize a significant
      capacity for holding ink and transferring them onto paper continuously and
      controllably. Inspired by this, a superhydrophobic/superaerophilic cone interface
      is developed to manipulate gas bubble size in aqueous media. When the resultant
      force between the Laplace force and the axial component of the buoyancy force
      approaches zero, the gas bubble is held steadily by the
      superhydrophobic/superaerophilic copper cones in a unique position (balance
      position). A new kind of pressure sensor is also designed based on this
      principle.

PMID- 29327914
TI  - Mechanistic Evaluation of Bioorthogonal Decaging with trans-Cyclooctene: The
      Effect of Fluorine Substituents on Aryl Azide Reactivity and Decaging from the
      1,2,3-Triazoline.
AB  - Bioorthogonal prodrug activation/decaging strategies need to be selective, rapid
      and release the drug from the masking group upon activation. The rates of the 1,3
      dipolar cycloaddition between a trans-cyclooctene (TCO) and a series of fluorine
      substituted azido-PABC self-immolative spacers caging two model drugs, and
      subsequent release from the 1,2,3-triazoline are reported. As the number of
      fluorine substituents on the PABC linker increases from one to four, the rate of
      cycloaddition increases by almost one order of magnitude. Using a combination of
      fluorescence, 1H/19F NMR, and computational experiments, we have been able to
      determine how substituents on the PABC ring can influence the degradation rates
      and also the product distribution of the 1,2,3-triazoline. We have also been able
      to determine how these substituents influence the rate of imine hydrolysis and
      1,6-self-immolation decaging rates of the generated anilines. The NMR and
      computational studies demonstrate that fluorine substituents on the aromatic ring
      lower the transition state energy required for converting the triazoline to the
      imine or aziridine intermediates via extrusion of diatomic nitrogen, and that in
      the case of a tetrafluoro substituted aromatic ring, it is the imine hydrolysis
      and 1,6-self-immolation that is rate-limiting. This knowledge further enhances
      the understanding of factors which influence the stability of triazolines, and
      enables potential applications of fluorinated aromatics, in particular,
      perfluorinated aromatics, in synthetic chemistry and sustained-release drug
      delivery systems.

PMID- 29327915
TI  - Multispectral Atomic Force Microscopy-Infrared Nano-Imaging of Malaria Infected
      Red Blood Cells.
AB  - Atomic force microscopy-infrared (AFM-IR) spectroscopy is a powerful new
      technique that can be applied to study molecular composition of cells and tissues
      at the nanoscale. AFM-IR maps are acquired using a single wavenumber value: they
      show either the absorbance plotted against a single wavenumber value or a ratio
      of two absorbance values. Here, we implement multivariate image analysis to
      generate multivariate AFM-IR maps and use this approach to resolve subcellular
      structural information in red blood cells infected with Plasmodium falciparum at
      different stages of development. This was achieved by converting the discrete
      spectral points into a multispectral line spectrum prior to multivariate image
      reconstruction. The approach was used to generate compositional maps of
      subcellular structures in the parasites, including the food vacuole, lipid
      inclusions, and the nucleus, on the basis of the intensity of hemozoin,
      hemoglobin, lipid, and DNA IR marker bands, respectively. Confocal Raman
      spectroscopy was used to validate the presence of hemozoin in the regions
      identified by the AFM-IR technique. The high spatial resolution of AFM-IR
      combined with hyperspectral modeling enables the direct detection of subcellular
      components, without the need for cell sectioning or immunological/biochemical
      staining. Multispectral-AFM-IR thus has the capacity to probe the phenotype of
      the malaria parasite during its intraerythrocytic development. This enables novel
      approaches to studying the mode of action of antimalarial drugs and the
      phenotypes of drug-resistant parasites, thus contributing to the development of
      diagnostic and control measures.

PMID- 29327916
TI  - Self-Assembly of Pseudorotaxane Structures from a Dicopper(II) Molecular Cage and
      Dicarboxylate Axles.
AB  - In this work, we employed for the first time a dinuclear bis[tris(2
      aminoethyl)amine] cryptate to obtain the self-assembly of pseudorotaxane
      structures in an aqueous solution. The goal was achieved by exploiting the well
      known affinity of the dicopper azacryptate with diphenyl spacers for the
      terephthalate anion. In particular, a series of molecular threads were
      synthesized by appending either alkyl or polyoxyethylene chains on both sides of
      the terephthalate benzene ring. The obtained dicarboxylic acids were precipitated
      as sodium salts, and their affinity toward the dicopper azacryptate was
      determined in a methanol/water mixture (pH 7). Experimental investigations showed
      that the chains' length and nature have a small impact on the 1:1 binding
      constants, whose values range between 4.98 and 5.18 log units. Computational
      studies indicated that the molecular axle is threaded through the azacryptate
      cavity, with the terephthalate group wedged between the two copper ions,
      coordinating both of them in the apical position (the one that, in the free
      azacryptate, is occupied by a water molecule). Compared to the inclusion complex
      with the plain terephthalate anion, a slight strain was found in the
      pseudorotaxane structure, induced by the inner chain of the thread inside the
      cavity. These results may be of great interest in all of the fields of science
      and technology in which host-guest recognition and molecular cages are applied.

PMID- 29327917
TI  - Peptide-Based Photoelectrochemical Cytosensor Using a Hollow-TiO2/EG/ZnIn2S4
      Cosensitized Structure for Ultrasensitive Detection of Early Apoptotic Cells and
      Drug Evaluation.
AB  - The ability to rapidly detect apoptotic cells and accurately evaluate therapeutic
      effects is significant in cancer research. To address this target, a
      biocompatible, ultrasensitive photoelectrochemical (PEC) cytosensing platform was
      developed based on electrochemically reduced graphene (EG)/ZnIn2S4 cosensitized
      TiO2 coupled with specific recognition between apoptotic cells and
      phosphatidylserine-binding peptide (PSBP). In this strategy, the HL-60 cells were
      selected as a model and C005, nilotinib, and imatinib were selected as apoptosis
      inducers to show cytosensing performances. In particular, a TiO2 photoactive
      substrate was designed as hollow spheres to enhance the PEC performance. Graphene
      was electrodeposited on the hollow TiO2-modified electrode to accelerate electron
      transfer and increase conductivity, followed by in situ growth of ZnIn2S4
      nanocrystals as photosensitizers via successive ionic layer adsorption and
      reaction method, forming a TiO2/EG/ZnIn2S4 cosensitized structure that was used
      as a PEC matrix to immobilize PSBP for the recognition of early apoptotic cells.
      The detection of apoptotic cells was based on steric hindrance originating from
      apoptotic cell capture to induce an obvious decrease in the photocurrent signal.
      The ultrahigh sensitivity of the cytosensor resulted from enhanced PEC
      performance, bioactivity, and high binding affinity between PSBP and apoptotic
      cells. Compared with other assays, incorporate toxic elements were avoided, such
      as Cd, Ru, and Te, which ensured normal cell growth and are appropriate for cell
      analysis. The designed PEC cytosensor showed a low detection limit of apoptotic
      cells (as low as three cells), a wide linear range from 1 * 103 to 5 * 107
      cells/mL, and an accurate evaluation of therapeutic effects. It also exhibited
      good specificity, reproducibility, and stability.

PMID- 29327913
TI  - Proteomic Analysis of the Downstream Signaling Network of PARP1.
AB  - Poly-ADP-ribosylation (PARylation) is a protein posttranslational modification
      (PTM) that is critically involved in many biological processes that are linked to
      cell stress responses. It is catalyzed by a class of enzymes known as poly-ADP
      ribose polymerases (PARPs). In particular, PARP1 is a nuclear protein that is
      activated upon sensing nicked DNA. Once activated, PARP1 is responsible for the
      synthesis of a large number of PARylated proteins and initiation of the DNA
      damage response mechanisms. This observation provided the rationale for
      developing PARP1 inhibitors for the treatment of human malignancies. Indeed,
      three PARP1 inhibitors (Olaparib, Rucaparib, and Niraparib) have recently been
      approved by the Food and Drug Administration for the treatment of ovarian cancer.
      Moreover, in 2017, both Olaparib and Niraparib have also been approved for the
      treatment of fallopian tube cancer and primary peritoneal cancer. Despite this
      very exciting progress in the clinic, the basic signaling mechanism that connects
      PARP1 to a diverse array of biological processes is still poorly understood. This
      is, in large part, due to the inherent technical difficulty associated with the
      analysis of protein PARylation, which is a low-abundance, labile, and
      heterogeneous PTM. The study of PARylation has been greatly facilitated by the
      recent advances in mass spectrometry-based proteomic technologies tailored to the
      analysis of this modification. In this Perspective, we discuss these
      breakthroughs, including their technical development, and applications that
      provide a global view of the many biological processes regulated by this
      important protein modification.

PMID- 29327918
TI  - Zeptomole Detection Scheme Based on Levitation Coordinate Measurements of a
      Single Microparticle in a Coupled Acoustic-Gravitational Field.
AB  - We present a novel analytical principle in which an analyte (according to its
      concentration) induces a change in the density of a microparticle, which is
      measured as a vertical coordinate in a coupled acoustic-gravitational (CAG)
      field. The density change is caused by the binding of gold nanoparticles (AuNP's)
      on a polystyrene (PS) microparticle through avidin-biotin association. The
      density of a 10-MUm PS particle increases by 2% when 500 100-nm AuNP's are bound
      to the PS. The CAG can detect this density change as a 5-10 MUm shift of the
      levitation coordinate of the PS. This approach, which allows us to detect 700
      AuNP's bound to a PS particle, is utilized to detect biotin in solution. Biotin
      is detectable at a picomolar level. The reaction kinetics plays a significant
      role in the entire process. The kinetic aspects are also quantitatively discussed
      based on the levitation behavior of the PS particles in the CAG field.

PMID- 29327919
TI  - Differentiation and Relative Quantitation of Disaccharide Isomers by MALDI
      TOF/TOF Mass Spectrometry.
AB  - Saccharide isomer differentiation has been a challenge in glycomics, as the lack
      of technology to decipher fully the diverse structures of compositions, linkages,
      and anomeric configurations. Several mass spectrometry-based methods have been
      applied to the discrimination of disaccharide isomers, but limited quantitative
      analyses have been reported. In the present study, MALDI-LIFT-TOF/TOF has been
      investigated to differentiate and relatively quantify underivatized glucose
      containing disaccharide isomers that differ in composition, connectivity or
      configuration. N-(1-naphthyl)ethylenediamine dihydrochloride (NEDC) was used as a
      highly sensitive matrix without matrix interferences in low mass range, thus
      yielding intense chloride-attached disaccharide ions [M + Cl]-, which could be
      fragmented to give diagnostic characteristic fragment patterns for distinguishing
      these isomers. Three different types of disaccharide isomers were successfully
      relatively quantified in a binary mixture using the specific product ion pairs.
      Finally, this method was utilized to identify and relatively quantify two
      disaccharide isomers in Medicago leaf (maltose and sucrose) without numerous
      preparation steps. In general, this method is a fast, effective, and robust
      method for rapid differentiation and quantitation of disaccharide isomers in
      complex medium.

PMID- 29327920
TI  - Generation of Optogenetically Modified Adenovirus Vector for Spatiotemporally
      Controllable Gene Therapy.
AB  - Gene therapy is expected to be utilized for the treatment of various diseases.
      However, the spatiotemporal resolution of current gene therapy technology is not
      high enough. In this study, we generated a new technology for spatiotemporally
      controllable gene therapy. We introduced optogenetic and CRISPR/Cas9 techniques
      into a recombinant adenovirus (Ad) vector, which is widely used in clinical
      trials and exhibits high gene transfer efficiency, to generate an illumination
      dependent spatiotemporally controllable gene regulation system (designated the
      Opt/Cas-Ad system). We generated an Opt/Cas-Ad system that could regulate a
      potential tumor suppressor gene, and we examined the effectiveness of this system
      in cancer treatment using a xenograft tumor model. With the Opt/Cas-Ad system,
      highly selective tumor treatment could be performed by illuminating the tumor. In
      addition, Opt/Cas-Ad system-mediated tumor treatment could be stopped simply by
      turning off the light. We believe that our Opt/Cas-Ad system can enhance both the
      safety and effectiveness of gene therapy.

PMID- 29327921
TI  - The Nature and Reactivity of Ferryl Heme in Compounds I and II.
AB  - Aerobic organisms have evolved to activate oxygen from the atmosphere, which
      allows them to catalyze the oxidation of different kinds of substrates. This
      activation of oxygen is achieved by a metal center (usually iron or copper)
      buried within a metalloprotein. In the case of iron-containing heme enzymes, the
      activation of oxygen is achieved by formation of transient iron-oxo (ferryl)
      intermediates; these intermediates are called Compound I and Compound II. The
      Compound I and II intermediates were first discovered in the 1930s in horseradish
      peroxidase, and it is now known that these same species are used across the
      family of heme enzymes, which include all of the peroxidases, the heme catalases,
      the P450s, cytochrome c oxidase, and NO synthase. Many years have passed since
      the first observations, but establishing the chemical nature of these transient
      ferryl species remains a fundamental question that is relevant to the reactivity,
      and therefore the usefulness, of these species in biology. This Account
      summarizes experiments that were conceived and conducted at Leicester and
      presents our ideas on the chemical nature, stability, and reactivity of these
      ferryl heme species. We begin by briefly summarizing the early milestones in the
      field, from the 1940s and 1950s. We present comparisons between the nature and
      reactivity of the ferryl species in horseradish peroxidase, cytochrome c
      peroxidase, and ascorbate peroxidase; and we consider different modes of electron
      delivery to ferryl heme, from different substrates in different peroxidases. We
      address the question of whether the ferryl heme is best formulated as an
      (unprotonated) FeIV?O or as a (protonated) FeIV-OH species. A range of
      spectroscopic approaches (EXAFS, resonance Raman, Mossbauer, and EPR) have been
      used over many decades to examine this question, and in the last ten years, X-ray
      crystallography has also been employed. We describe how information from all of
      these studies has blended together to create an overall picture, and how the
      recent application of neutron crystallography has directly identified protonation
      states and has helped to clarify the precise nature of the ferryl heme in
      cytochrome c peroxidase and ascorbate peroxidase. We draw comparisons between the
      Compound I and Compound II species that we have observed in peroxidases with
      those found in other heme systems, notably the P450s, highlighting possible
      commonality across these heme ferryl systems. The identification of proton
      locations from neutron structures of these ferryl species opens the door for
      understanding the proton translocations that need to occur during O-O bond
      cleavage.

PMID- 29327922
TI  - A Constrained Tetrapeptide as a Model of Cu(I) Binding Sites Involving Cu4S6
      Clusters in Proteins.
AB  - Peptide design is an efficient strategy to create relevant models of natural
      metal binding sites found in proteins. The two short tetrapeptides Ac-Cys-dPro
      Pro-Cys-NH2 (CdPPC) and Ac-Cys-Pro-Gly-Cys-NH2 (CPGC) were synthesized and
      studied as mimics of Cu(I) binding sites involved in Cu homeostasis. Both
      sequences contain beta turn inducing motifs to rigidify the peptide backbone
      structure and thereby preorganize the metal-binding side chains. The more
      constrained structure of the peptide CdPPC with respect to CPGC was evidenced by
      the measurements of the temperature coefficients of the amide protons by 1H NMR,
      which suggest a solvent-shielded intramolecular hydrogen bond in CdPPC, and no H
      bond in CPGC. The Cu(I) complexes were studied by UV, circular dichroism (CD),
      and NMR spectroscopies as well as electrospray ionization mass spectrometry (ESI
      MS) experiments in aqueous solution at physiological pH. The complexes formed
      with CPGC showed a complicated speciation with the possible formation of many
      polymetallic species. By contrast, the better preorganization in CdPPC leads to
      the formation of a unique Cu4L3 complex involving a Cu4S6 core. The formation of
      this specific cluster was confirmed by ESI-MS and by diffusion-ordered NMR
      spectroscopy in solution. The affinity of CdPPC for Cu(I) (beta11pH7.4 = 1017.5
      calculated for a CuL complex) is more than 1 order of magnitude larger than the
      affinity measured for the less constrained peptide CPGC. Besides, this stability
      constant value is very similar to those reported with proteins. Therefore, the
      Cu(I) complex formed with the simple tetrapeptide CdPPC in water at physiological
      pH represents a very good model of Cu(I)-thiolate clusters found in proteins. The
      extremely large selectivity (1011) in favor of Cu(I) with respect to Zn(II), an
      abundant competitor in cells, makes it a promising candidate to be targeted to
      the liver cells for the localized treatment of Cu overload in Wilson's disease.

PMID- 29327923
TI  - Aliovalent Cation Substitution in UO2: Electronic and Local Structures of U1
      yLayO2+/-x Solid Solutions.
AB  - For nuclear fuel related applications, the oxygen stoichiometry of mixed oxides
      U1-yMyO2+/-x is an essential property as it affects fuel properties and may
      endanger the safe operation of nuclear reactors. A careful review of the open
      literature indicates that this parameter is difficult to assess properly and that
      the nature of the defects, i.e., oxygen vacancies or UV, in aliovalent cation
      doped UO2 is still subject to controversy. To confirm the formation of UV, we
      have investigated the room-temperature stable U1-yLayO2+/-x phase using several
      experimental methods (e.g., XRD, XANES, and NMR) confirmed by theoretical
      calculations. This paper presents the experimental proof of UV and its effect we
      identified in both electronic and local structure. We observe that UV is formed
      in quasi-equimolar proportion as LaIII in U1-yLayO2+/-x (y = 0.06, 0.11, and
      0.22) solid solutions. The fluorite structure is maintained despite the cationic
      substitution, but the local structure is affected as variations of the
      interatomic distances are found. Therefore, we provide here the definitive proof
      that the substitution of UIV with LaIII is not accommodated by the creation of O
      vacancies as has often been assumed. The UO2 fluorite structure compensates the
      incorporation of an aliovalent cation by the formation of UV in quasi-equimolar
      proportions.

PMID- 29327924
TI  - Two-Step Macrocycle Synthesis by Classical Ugi Reaction.
AB  - The direct nonpeptidic macrocycle synthesis of alpha-isocyano-omega-amines via
      the classical Ugi four-component reaction (U-4CR) is introduced. Herein an
      efficient and flexible two-step procedure to complex macrocycles is reported. In
      the first step, the reaction between unprotected diamines and isocyanocarboxylic
      acids gives high diversity of unprecedented building blocks in high yield. In the
      next step, the alpha-isocyano-omega-amines undergo a U-4CR with high diversity of
      aldehydes and carboxylic acids in a one-pot procedure. This synthetic approach is
      short and efficient and leads to a wide range of macrocycles with different ring
      sizes.

PMID- 29327925
TI  - Writing Theory and Modeling Papers for Langmuir: The Good, the Bad, and the Ugly.

PMID- 29327926
TI  - Electrochemical Reaction Mechanism of the MoS2 Electrode in a Lithium-Ion Cell
      Revealed by in Situ and Operando X-ray Absorption Spectroscopy.
AB  - As a typical transition metal dichalcogenide, MoS2 offers numerous advantages for
      nanoelectronics and electrochemical energy storage due to its unique layered
      structure and tunable electronic properties. When used as the anode in lithium
      ion cells, MoS2 undergoes intercalation and conversion reactions in sequence upon
      lithiation, and the reversibility of the conversion reaction is an important but
      still controversial topic. Here, we clarify unambiguously that the conversion
      reaction of MoS2 is not reversible, and the formed Li2S is converted to sulfur in
      the first charge process. Li2S/sulfur becomes the main redox couple in the
      subsequent cycles and the main contributor to the reversible capacity. In
      addition, due to the insulating nature of both Li2S and sulfur, a strong
      relaxation effect is observed during the cycling process. This study clearly
      reveals the electrochemical lithiation-delithiation mechanism of MoS2, which can
      facilitate further developments of high-performance MoS2-based electrodes.

PMID- 29327927
TI  - Atom-Dependent Edge-Enhanced Second-Harmonic Generation on MoS2 Monolayers.
AB  - Edge morphology and lattice orientation of single-crystal molybdenum disulfide
      (MoS2) monolayers, a transition metal dichalcogenide (TMD), possessing a
      triangular shape with different edges grown by chemical vapor deposition are
      characterized by atomic force microscopy and transmission electron microscopy.
      Multiphoton laser scanning microscopy is utilized to study one-dimensional atomic
      edges of MoS2 monolayers with localized midgap electronic states, which result in
      greatly enhanced optical second-harmonic generation (SHG). Microscopic S-zigzag
      edge and S-Mo Klein edge (bare Mo atoms protruding from a S-zigzag edge)
      terminations and the edge-atom dependent resonance energies can therefore be
      deduced based on SHG images. Theoretical calculations based on density functional
      theory clearly explain the lower energy of the S-zigzag edge states compared to
      the corresponding S-Mo Klein edge states. Characterization of the atomic-scale
      variation of edge-enhanced SHG is a step forward in this full-optical and high
      yield technique of atomic-layer TMDs.

PMID- 29327929
TI  - Development of Candidates for Positron Emission Tomography (PET) Imaging of
      Ghrelin Receptor in Disease: Design, Synthesis, and Evaluation of Fluorine
      Bearing Quinazolinone Derivatives.
AB  - Molecular imaging with positron emission tomography (PET) is an attractive
      platform for noninvasive detection and assessment of disease. The development of
      a PET imaging agent targeting the ghrelin receptor (growth hormone secretagogue
      receptor type 1a or GHS-R1a) has the potential to lead to the detection and
      assessment of the higher than normal expression of GHS-R1a in diseases such as
      prostate, breast, and ovarian cancer. To enable the development of 18F
      radiopharmaceuticals, we have designed and synthesized three series of
      quinazolinone derivatives, resulting in the identification of two compound (5i,
      17) with subnanomolar binding affinity and one fluorine-bearing compound (10b)
      with picomolar binding affinity (20 pM), representing the highest binding
      affinity for GHS-R1a reported to date. Two lead compounds (5b, IC50 = 20.6 nM;
      5e, IC50 = 9.3 nM) were successfully 18F-radiolabeled with radiochemical purity
      of greater than 99%. Molecular modeling studies were performed to shed light on
      ligand-receptor interactions.

PMID- 29327928
TI  - One-Step Bioconversion of Fatty Acids into C8-C9 Volatile Aroma Compounds by a
      Multifunctional Lipoxygenase Cloned from Pyropia haitanensis.
AB  - The multifunctional lipoxygenase PhLOX cloned from Pyropia haitanensis was
      expressed in Escherichia coli with 24.4 mg.L-1 yield. PhLOX could catalyze the
      one-step bioconversion of C18-C22 fatty acids into C8-C9 volatile organic
      compounds (VOCs), displaying higher catalytic efficiency for eicosenoic and
      docosenoic acids than for octadecenoic acids. C20:5 was the most suitable
      substrate among the tested fatty acids. The C8-C9 VOCs were generated in good
      yields from fatty acids, e.g., 2E-nonenal from C20:4, and 2E,6Z-nonadienal from
      C20:5. Hydrolyzed oils were also tested as substrates. The reactions mainly
      generated 2E,4E-pentadienal, 2E-octenal, and 2E,4E-octadienal from hydrolyzed
      sunflower seed oil, corn oil, and fish oil, respectively. PhLOX showed good
      stability after storage at 4  degrees C for 2 weeks and broad tolerance to pH and
      temperature. These desirable properties of PhLOX make it a promising novel
      biocatalyst for the industrial production of volatile aroma compounds.

PMID- 29327930
TI  - Synthesis of Cyclic Enones by Allyl-Palladium-Catalyzed alpha,beta
      Dehydrogenation.
AB  - The use of allyl-palladium catalysis for the one-step alpha,beta-dehydrogenation
      of ketones via their zinc enolates is reported. The optimized protocol utilizes
      commercially available Zn(TMP)2 as base and diethyl allyl phosphate as oxidant.
      Notably, this transformation operates under salt-free conditions and tolerates a
      diverse scope of cycloalkanones.

PMID- 29327931
TI  - Bastimolide B, an Antimalarial 24-Membered Marine Macrolide Possessing a tert
      Butyl Group.
AB  - We reported previously the discovery of the potent antimalarial 40-membered
      macrolide bastimolide A (1) from the tropical marine cyanobacterium Okeania
      hirsute. Continued investigation has led to the discovery of a new analogue,
      bastimolide B (2), a 24-membered polyhydroxy macrolide with a long aliphatic
      chain and unique terminal tert-butyl group. Its complete structure was determined
      by a combination of extensive spectroscopic methods and comparative analysis of
      its methanolysis products with those of bastimolide A. A methanolysis mechanism
      for bastimolide A is proposed, and one unexpected isomerization product of the C2
      C3 double bond, 2-(E)-bastimolide A (3), was obtained. Bastimolide B (2) showed
      strong antimalarial activity against chloroquine-sensitive Plasmodium falciparum
      strain HB3. A preliminary investigation of the structure-activity relationship
      based on six analogues revealed the importance of the double bond as well as the
      1,3-diol and 1,3,5-triol functionalities.

PMID- 29327932
TI  - Temperature Controlled Selective C-S or C-C Bond Formation: Photocatalytic
      Sulfonylation versus Arylation of Unactivated Heterocycles Utilizing Aryl
      Sulfonyl Chlorides.
AB  - A visible-light-induced photocatalytic method for the arylsulfonylation of
      heterocycles has been developed. The synthetic utility of this reaction is
      reflected by the direct use of commercially available sulfonyl chlorides and
      heterocycles under room temperature conditions. Complementarily, the
      photocatalytic arylation of heterocycles by sulfonyl chlorides via extrusion of
      SO2 is feasible at elevated temperature conditions, allowing switching between
      arylation or arylsulfonylation with excellent chemoselectivity.

PMID- 29327933
TI  - Ligand-Effect in Gold(I)-Catalyzed Rautenstrauch Rearrangement: Regio- and
      Stereoselective Synthesis of Bicyclo[3.2.1]octa-3,6-dienes through
      Cyclodimerization of 1-Ethynyl-2-propenyl Esters.
AB  - Gold(I) complexes bearing sterically demanding phosphine ligands such as tBuXphos
      catalyze the cascade Rautenstrauch rearrangement/[4 + 3] cycloaddition of 1
      ethynyl-2-propenyl esters. The reaction provides an efficient and straightforward
      route to bicyclo[3.2.1]octa-3,6-dienes with high regio- and stereoselectivity.
      The formation of the [4 + 3] cycloadducts likely proceeds through the
      cycloaddition of a gold(I) carbenoid/gold-stabilized allyl cation intermediate
      with cyclopentadiene arising from Rautenstrauch rearrangement.

PMID- 29327934
TI  - Synthesis of Pyrrole-2-carbaldehyde Derivatives by Oxidative Annulation and
      Direct Csp3-H to C?O Oxidation.
AB  - An efficient and practical de novo synthesis of pyrrole-2-carbaldehyde skeletons
      featuring oxidative annulation and Csp3-H to C?O oxidation is presented,
      exemplified by the preparation of pyrrole-2-carbaldehyde derivatives from aryl
      methyl ketones, arylamines, and acetoacetate esters. Preliminary mechanistic
      investigations indicate that the aldehyde oxygen atom originates from oxygen.
      Moreover, the developed scalable approach provides a distinct advantage over
      traditional oxidative functionalization of C-H moieties, avoiding the use of
      stoichiometric quantities of hazardous oxidants.

PMID- 29327936
TI  - A Simple "Boxed Molecular Kinetics" Approach To Accelerate Rare Events in the
      Stochastic Kinetic Master Equation.
AB  - The chemical master equation is a powerful theoretical tool for analyzing the
      kinetics of complex multiwell potential energy surfaces in a wide range of
      different domains of chemical kinetics spanning combustion, atmospheric
      chemistry, gas-surface chemistry, solution phase chemistry, and biochemistry.
      There are two well-established methodologies for solving the chemical master
      equation: a stochastic "kinetic Monte Carlo" approach and a matrix-based
      approach. In principle, the results yielded by both approaches are identical; the
      decision of which approach is better suited to a particular study depends on the
      details of the specific system under investigation. In this Article, we present a
      rigorous method for accelerating stochastic approaches by several orders of
      magnitude, along with a method for unbiasing the accelerated results to recover
      the "true" value. The approach we take in this paper is inspired by the so-called
      "boxed molecular dynamics" (BXD) method, which has previously only been applied
      to accelerate rare events in molecular dynamics simulations. Here we extend BXD
      to design a simple algorithmic strategy for accelerating rare events in
      stochastic kinetic simulations. Tests on a number of systems show that the
      results obtained using the BXD rare event strategy are in good agreement with
      unbiased results. To carry out these tests, we have implemented a kinetic Monte
      Carlo approach in MESMER, which is a cross-platform, open-source, and freely
      available master equation solver.

PMID- 29327935
TI  - Introduction of a Crystalline, Shelf-Stable Reagent for the Synthesis of
      Sulfur(VI) Fluorides.
AB  - The design, synthesis, and application of [4-(acetylamino)phenyl]imidodisulfuryl
      difluoride (AISF), a shelf-stable, crystalline reagent for the synthesis of
      sulfur(VI) fluorides, is described. The utility of AISF is demonstrated in the
      synthesis of a diverse array of aryl fluorosulfates and sulfamoyl fluorides under
      mild conditions. Additionally, a single-step preparation of AISF was developed
      that installed the bis(fluorosulfonyl)imide group on acetanilide utilizing an
      oxidative C-H functionalization protocol.

PMID- 29327937
TI  - Synthesis, Structure, and Properties of Corona[6]arenes and Their Assembly with
      Anions in the Crystalline State.
AB  - The synthesis, conformational structure, electronic property, and anion
      complexation of novel coronarenes were systematically studied. A number of
      corona[4]arene[2]tetrazines that contain different combinations of nitrogen atoms
      with O, S, SO2, and CH2 as bridging units were synthesized conveniently by means
      of a fragment coupling strategy based on efficient nucleophilic aromatic
      substitution reaction of easily available aromatic dinucleophiles and 3,6
      dichlorotetrazine. The resulting macrocycles adopt crownlike conformational
      structures with the nitrogen bridge(s) forming conjugation with carbonyl and the
      other heteroatom linkages with tetrazine. CV and DPV measurements showed that the
      tetrazine-bearing coronarenes were electron deficient with reduction potentials
      ranging from -896 to -960 mV. Owing mainly to noncovalent anion-pi attractive
      interactions, N2,O4-corona[4]arene[2]tetrazine formed complexes with anions of
      varied geometries and shapes yielding diverse assembled structures in the solid
      state.

PMID- 29327938
TI  - Glaucocalyxin A Attenuates the Activation of Hepatic Stellate Cells Through the
      TGF-beta1/Smad Signaling Pathway.
AB  - Glaucocalyxin A (GLA) is a biologically active ent-kauranoid diterpenoid isolated
      from Rabdosia japonica var. glaucocalyx. A large number of studies have shown
      that GLA possesses important pharmacological activities, such as anti
      inflammatory, antitumor, antifibrosis, and antiplatelet activities. However, the
      role of GLA in the pathogenesis of liver fibrosis remains undefined. Therefore,
      the aim of this study was to investigate the effects of GLA on hepatic stellate
      cells (HSCs) activation/proliferation and migration in vitro and its possible
      mechanism in liver fibrosis. HSCs were incubated with different concentrations of
      GLA in the presence or absence of TGF-beta1 for 24 h. Cell proliferation and
      migration were evaluated by the MTT assay and Transwell migration assay,
      respectively. Intracellular reactive oxygen species (ROS) production was measured
      using 2',7'-dichlorodihydrofluorescin diacetate (DCFH-DA). Western blot was used
      to detect the expression levels of alpha-smooth-muscle actin (alpha-SMA),
      collagen-I, p-Smad2, Smad2, p-Smad3, and Smad3. Our results demonstrated that GLA
      significantly inhibited the proliferation and migration of HSCs, and suppressed
      the expression of extracellular matrix in TGF-beta1-stimulated HSC-T6 cells. In
      addition, pretreatment with GLA markedly suppressed TGF-beta1-induced ROS level
      in HSC-T6 cells. Furthermore, GLA greatly inhibited the phosphorylation levels of
      Smad2 and Smad3 in TGF-beta1-stimulated HSC-T6 cells. Taken together, these
      findings indicated that GLA inhibits the proliferation and activation of HSC-T6
      cells, at least in part, through the TGF-beta1/Smad signaling pathway. Therefore,
      GLA may be a promising potential therapeutic agent for liver fibrosis.

PMID- 29327939
TI  - Blockade of the Complement C5a/C5aR1 Axis Impairs Lung Cancer Bone Metastasis by
      CXCL16-mediated Effects.
AB  - RATIONALE: C5aR1 (CD88), a receptor for complement anaphylatoxin C5a, is a potent
      immune mediator. Its impact on malignant growth and dissemination of non-small
      cell lung cancer cells is poorly understood. OBJECTIVES: To investigate the
      contribution of the C5a/C5aR1 axis to the malignant phenotype of non-small cell
      lung cancer cells, particularly in skeletal colonization, a preferential lung
      metastasis site. METHODS: Association between C5aR1 expression and clinical
      outcome was assessed in silico and validated by immunohistochemistry. Functional
      significance was evaluated by lentiviral gene silencing and ligand l-aptamer
      inhibition in in vivo models of lung cancer bone metastasis. In vitro functional
      assays for signaling, migration, invasion, metalloprotease activity, and
      osteoclastogenesis were also performed. MEASUREMENTS AND MAIN RESULTS: High
      levels of C5aR1 in human lung tumors were significantly associated with shorter
      recurrence-free survival, overall survival, and bone metastasis. Silencing of
      C5aR1 in lung cancer cells led to a substantial reduction in skeletal metastatic
      burden and osteolysis in in vivo models. Furthermore, metalloproteolytic,
      migratory, and invasive tumor cell activities were modulated in vitro by C5aR1
      stimulation or gene silencing. l-Aptamer blockade or C5aR1 silencing
      significantly reduced the osseous metastatic activity of lung cancer cells in
      vivo. This effect was associated with decreased osteoclastogenic activity in
      vitro and was rescued by the exogenous addition of the chemokine CXCL16.
      CONCLUSIONS: Disruption of C5aR1 signaling in lung cancer cells abrogates their
      tumor-associated osteoclastogenic activity, impairing osseous colonization. This
      study unveils the role played by the C5a/C5aR1 axis in lung cancer dissemination
      and supports its potential use as a novel therapeutic target.

PMID- 29327940
TI  - The different faces of renal angiomyolipomas on radiologic imaging: a pictorial
      review.
AB  - Renal angiomyolipoma (AML) is an uncommon renal tumour, generally composed of
      mature adipose tissue, dysmorphic blood vessels and smooth muscle. Identification
      of intratumoral fat on unenhanced CT images is the most reliable finding for
      establishing the diagnosis of renal AML. However, AMLs sometimes exhibit atypical
      findings, including cystic as well as solid forms; some of these variants overlap
      with the appearance of other renal tumours. A rare type of AML, the epithelioid
      type, possesses malignant potential. The aim of this pictorial review is to
      gather the different imaging features of AMLs including the classic and fat-poor
      types, AMLs with epithelial cysts, epithelioid AML, AML associated with tuberous
      sclerosis, haemorrhagic AML and large AMLs mimicking retroperitoneal
      liposarcomas. The diagnostic clues that help to distinguish AMLs from other renal
      tumours are also described in the review.

PMID- 29327942
TI  - Efficient selective screening for heart failure in elderly men and women from the
      community: A diagnostic individual participant data meta-analysis.
AB  - Background Prevalence of undetected heart failure in older individuals is high in
      the community, with patients being at increased risk of morbidity and mortality
      due to the chronic and progressive nature of this complex syndrome. An essential,
      yet currently unavailable, strategy to pre-select candidates eligible for
      echocardiography to confirm or exclude heart failure would identify patients
      earlier, enable targeted interventions and prevent disease progression. The aim
      of this study was therefore to develop and validate such a model that can be
      implemented clinically. Methods and results Individual patient data from four
      primary care screening studies were analysed. From 1941 participants >60 years
      old, 462 were diagnosed with heart failure, according to criteria of the European
      Society of Cardiology heart failure guidelines. Prediction models were developed
      in each cohort followed by cross-validation, omitting each of the four cohorts in
      turn. The model consisted of five independent predictors; age, history of
      ischaemic heart disease, exercise-related shortness of breath, body mass index
      and a laterally displaced/broadened apex beat, with no significant interaction
      with sex. The c-statistic ranged from 0.70 (95% confidence interval (CI) 0.64
      0.76) to 0.82 (95% CI 0.78-0.87) at cross-validation and the calibration was
      reasonable with Observed/Expected ratios ranging from 0.86 to 1.15. The clinical
      model improved with the addition of N-terminal pro B-type natriuretic peptide
      with the c-statistic increasing from 0.76 (95% CI 0.70-0.81) to 0.89 (95% CI 0.86
      0.92) at cross-validation. Conclusion Easily obtainable patient characteristics
      can select older men and women from the community who are candidates for
      echocardiography to confirm or refute heart failure.

PMID- 29327941
TI  - Infection Is Not Required for Mucoinflammatory Lung Disease in CFTR-Knockout
      Ferrets.
AB  - RATIONALE: Classical interpretation of cystic fibrosis (CF) lung disease
      pathogenesis suggests that infection initiates disease progression, leading to an
      exuberant inflammatory response, excessive mucus, and ultimately bronchiectasis.
      Although symptomatic antibiotic treatment controls lung infections early in
      disease, lifelong bacterial residence typically ensues. Processes that control
      the establishment of persistent bacteria in the CF lung, and the contribution of
      noninfectious components to disease pathogenesis, are poorly understood.
      OBJECTIVES: To evaluate whether continuous antibiotic therapy protects the CF
      lung from disease using a ferret model that rapidly acquires lethal bacterial
      lung infections in the absence of antibiotics. METHODS: CFTR (cystic fibrosis
      transmembrane conductance regulator)-knockout ferrets were treated with three
      antibiotics from birth to several years of age and lung disease was followed by
      quantitative computed tomography, BAL, and histopathology. Lung disease was
      compared with CFTR-knockout ferrets treated symptomatically with antibiotics.
      MEASUREMENTS AND MAIN RESULTS: Bronchiectasis was quantified from computed
      tomography images. BAL was evaluated for cellular differential and features of
      inflammatory cellular activation, bacteria, fungi, and quantitative proteomics.
      Semiquantitative histopathology was compared across experimental groups. We
      demonstrate that lifelong antibiotics can protect the CF ferret lung from
      infections for several years. Surprisingly, CF animals still developed hallmarks
      of structural bronchiectasis, neutrophil-mediated inflammation, and mucus
      accumulation, despite the lack of infection. Quantitative proteomics of BAL from
      CF and non-CF pairs demonstrated a mucoinflammatory signature in the CF lung
      dominated by Muc5B and neutrophil chemoattractants and products. CONCLUSIONS:
      These findings implicate mucoinflammatory processes in the CF lung as pathogenic
      in the absence of clinically apparent bacterial and fungal infections.

PMID- 29327943
TI  - Phenotyping Pharyngeal Pathophysiology using Polysomnography in Patients with
      Obstructive Sleep Apnea.
AB  - RATIONALE: Therapies for obstructive sleep apnea (OSA) could be administered on
      the basis of a patient's own phenotypic causes ("traits") if a clinically
      applicable approach were available. OBJECTIVES: Here we aimed to provide a means
      to quantify two key contributors to OSA-pharyngeal collapsibility and
      compensatory muscle responsiveness-that is applicable to diagnostic
      polysomnography. METHODS: Based on physiological definitions, pharyngeal
      collapsibility determines the ventilation at normal (eupneic) ventilatory drive
      during sleep, and pharyngeal compensation determines the rise in ventilation
      accompanying a rising ventilatory drive. Thus, measuring ventilation and
      ventilatory drive (e.g., during spontaneous cyclic events) should reveal a
      patient's phenotypic traits without specialized intervention. We demonstrate this
      concept in patients with OSA (N = 29), using a novel automated noninvasive method
      to estimate ventilatory drive (polysomnographic method) and using "gold standard"
      ventilatory drive (intraesophageal diaphragm EMG) for comparison. Specialized
      physiological measurements using continuous positive airway pressure manipulation
      were employed for further comparison. The validity of nasal pressure as a
      ventilation surrogate was also tested (N = 11). MEASUREMENTS AND MAIN RESULTS:
      Polysomnography-derived collapsibility and compensation estimates correlated
      favorably with those quantified using gold standard ventilatory drive (R = 0.83,
      P < 0.0001; and R = 0.76, P < 0.0001; respectively) and using continuous positive
      airway pressure manipulation (R = 0.67, P < 0.0001; and R = 0.64, P < 0.001;
      respectively). Polysomnographic estimates effectively stratified patients into
      high versus low subgroups (accuracy, 69-86% vs. ventilatory drive measures; P <
      0.05). Traits were near-identical using nasal pressure versus pneumotach (N = 11,
      R >= 0.98, both traits; P < 0.001). CONCLUSIONS: Phenotypes of pharyngeal
      dysfunction in OSA are evident from spontaneous changes in ventilation and
      ventilatory drive during sleep, enabling noninvasive phenotyping in the clinic.
      Our approach may facilitate precision therapeutic interventions for OSA.

PMID- 29327945
TI  - The gas bubble sign-a reliable indicator of laryngeal fractures in hanging on
      post-mortem CT.
AB  - OBJECTIVE: The purpose was to evaluate the presence of gas in the tissue adjacent
      to the laryngeal structures, "the gas bubble sign", in cases of hanging as a
      diagnostic indicator of neck trauma. METHODS: In this study, post-mortem CT
      (PMCT) scans and autopsies of 35 victims of hanging were examined to reveal age
      dependent changes, laryngeal fracture, fracture location and the presence of gas.
      A matched group with cardiac arrest or intoxication was used as controls (n =
      35). An autopsy was performed in each case. RESULTS: Incomplete suspension was
      the most common method in hanging. The thyroid horns (90.5%) were identified as
      the most vulnerable location for fractures. Laryngeal deformity and dislocation,
      which was only detected on PMCT, was observed in 57.1% and was concomitant with
      fractures in 83.3%. Laryngeal fractures are more common with advanced age (>40
      years, 88.9%) and less common in younger subjects (<40 years, 29.4%). The gas
      bubble sign with regard to laryngeal fractures yielded a sensitivity of 79.2%, a
      positive predictive value of 95%, a specificity of 90.9%, a negative predictive
      value of 34.5% and an accuracy of 83%. CONCLUSION: The complex evaluation of the
      larynx is profoundly supported by PMCT and the detection of the gas bubble sign
      as a diagnostic indicator of neck trauma. This relevant diagnostic finding might
      aid in not only post-mortem cases but also clinical cases, for patients who
      survive an assault to the neck. Advances in knowledge: (1) The gas bubble sign is
      a diagnostic indicator of neck trauma in not putrefied bodies. (2) PMCT supports
      evaluation of trauma to the neck in hanging tremendously. (3) The diagnostic
      finding of gas located at the laryngeal structures may not only aid in post
      mortem cases but also clinical cases of people who survive an assault to the
      neck.

PMID- 29327944
TI  - Diagnostic accuracy of 18F-FDG PET or PET/CT for the characterization of adrenal
      masses: a systematic review and meta-analysis.
AB  - OBJECTIVE: We aimed to explore the role of the diagnostic accuracy of 18F
      fluodeoxyglucose PET (18F-FDG PET) or PET/CT for characterization of adrenal
      lesions through a systematic review and meta-analysis. METHODS: The MEDLINE,
      EMBASE, and Cochrane Library database, from the earliest available date of
      indexing through 30 April 2017, were searched for studies evaluating the
      diagnostic performance of 18F-FDG PET or PET/CT for characterization of adrenal
      lesions. We determined the sensitivities and specificities across studies,
      calculated positive and negative likelihood ratios (LR + and LR-), and
      constructed summary receiver operating characteristic curves. RESULTS: Across 29
      studies (2421 patients), the pooled sensitivity for 18F-FDG PET or PET/CT was
      0.91 [95% CI (0.88-0.94)] with heterogeneity (chi2 = 141.8, p = 0.00) and a
      pooled specificity of 0.91 [95% CI (0.87-0.93)] with heterogeneity (chi2 = 113.7,
      p = 0.00). Likelihood ratio (LR) syntheses gave an overall positive likelihood
      ratio (LR+) of 9.9 [95% CI (7.1-13.7)] and negative likelihood ratio (LR-) of
      0.09 [95% CI (0.07-0.13)]. The pooled diagnostic odds ratio was 105 [95% CI (63
      176)]. In metaregression analysis, study design, publication year, study location
      (western vs others), interpretation criteria of PET or PET/CT images,
      quantification of PET or PET/CT [SUVmax (maximum standardized uptake value) vs
      SUV (standardized uptake value) ratio], patient group, and analysis method
      (patient-based vs lesion-based) were the sources of the study heterogeneity.
      However, in multivariate metaregression, no definite variable was the source of
      the study heterogeneity. CONCLUSION: 18F-FDG PET or PET/CT demonstrated good
      sensitivity and specificity for the characterization of adrenal masses. At
      present, the literature regarding the use of 18F-FDG PET or PET/CT for the
      characterization of adrenal masses remains still limited; thus, further large
      multicenter studies would be necessary to substantiate the diagnostic accuracy of
      18F-FDG PET or PET/CT characterization of adrenal masses. Advances in knowledge:
      18F- FDG PET or PET/CT showed good sensitivity and specificity for the
      characterization of adrenal masses and could provide additional information for
      that purpose.

PMID- 29327946
TI  - Posttranscriptional Regulation of Human Antigen R by miR-133b Enhances Docetaxel
      Cytotoxicity Through the Inhibition of ATP-Binding Cassette Subfamily G Member 2
      in Prostate Cancer Cells.
AB  - Docetaxel (DTX)-based chemotherapy is a first-line therapy in patients with
      castration-resistant prostate cancer. However, development of DTX resistance
      remains a challenge in cancer treatment. miRNAs have been shown to be involved in
      drug resistance in tumors. Nevertheless, little is known about the function and
      detailed molecular mechanism of miR-133b in DTX resistance of prostate cancer
      cells. The current study showed that miR-133b was downregulated, while human
      antigen R (HuR) was upregulated in prostate cancer cells. HuR was identified as a
      target of miR-133b, and miR-133b could suppress HuR expression. Ectopic
      expression of miR-133b and HuR knockdown suppressed cell viability and promoted
      DTX-induced apoptosis in DTX-treated prostate cancer cells, which were restored
      by HuR overexpression. Furthermore, HuR overexpression partially abolished the
      inhibitory effect of miR-133b overexpression on ATP-binding cassette (ABC)
      subfamily G member 2 (ABCG2) expression in prostate cancer cells. ABCG2
      overexpression relieved DTX and miR-133b cytotoxicity in prostate cancer cells.
      In conclusion, posttranscriptional regulation of HuR by miR-133b enhances DTX
      cytotoxicity through inhibition of ABCG2, revealing a novel miR-133b/HuR/ABCG2
      regulatory pathway to overcome chemoresistance in prostate cancer cells.

PMID- 29327947
TI  - Secnidazole: next-generation antimicrobial agent for bacterial vaginosis
      treatment.
AB  - Secnidazole is a next-generation 5-nitroimidazole approved for more than three
      decades in Europe, Asia, South America and Africa and recently in the USA as a
      single-dose (2 g) treatment of bacterial vaginosis (BV). Secnidazole is
      characterized by potent in vitro antimicrobial activity against BV-associated
      pathogens, as well as prolonged terminal elimination half-life and systemic
      exposure. These characteristics form the basis of effective and safe treatment of
      BV with a 2-g single-dose secnidazole regimen, which was recently confirmed in
      double-blind, placebo-controlled clinical trials conducted in the USA. The option
      to treat BV with single-dose secnidazole not only cures the primary infection but
      also may diminish risks of serious sequelae of untreated or undertreated
      infection.

PMID- 29327948
TI  - Effects of Lumacaftor-Ivacaftor Therapy on Cystic Fibrosis Transmembrane
      Conductance Regulator Function in Phe508del Homozygous Patients with Cystic
      Fibrosis.
AB  - RATIONALE: The combination of the CFTR (cystic fibrosis transmembrane conductance
      regulator) corrector lumacaftor with the potentiator ivacaftor has been approved
      for the treatment of patients with cystic fibrosis homozygous for the Phe508del
      CFTR mutation. The phase 3 trials examined clinical outcomes but did not evaluate
      CFTR function in patients. OBJECTIVES: To examine the effect of lumacaftor
      ivacaftor on biomarkers of CFTR function in Phe508del homozygous patients with
      cystic fibrosis aged 12 years and older. METHODS: This prospective observational
      study assessed clinical outcomes including FEV1% predicted and body mass index,
      and CFTR biomarkers including sweat chloride concentration, nasal potential
      difference, and intestinal current measurement before and 8-16 weeks after
      initiation of lumacaftor-ivacaftor. MEASUREMENTS AND MAIN RESULTS: A total of 53
      patients were enrolled in the study, and 52 patients had baseline and follow-up
      measurements. After initiation of lumacaftor-ivacaftor sweat chloride
      concentrations were reduced by 17.8 mmol/L (interquartile range [IQR], -25.9 to 
      6.1; P < 0.001), nasal potential difference showed partial rescue of CFTR
      function in nasal epithelia to a level of 10.2% (IQR, 0.0-26.1; P < 0.011), and
      intestinal current measurement showed functional improvement in rectal epithelia
      to a level of 17.7% of normal (IQR, 10.8-29.0; P < 0.001). All patients improved
      in at least one CFTR biomarker, but no correlations were found between CFTR
      biomarker responses and clinical outcomes. CONCLUSIONS: Lumacaftor-ivacaftor
      results in partial rescue of Phe508del CFTR function to levels comparable to the
      lower range of CFTR activity found in patients with residual function mutations.
      Functional improvement was detected even in the absence of short-term improvement
      of FEV1% predicted and body mass index. Clinical trial registered with
      www.clinicaltrials.gov (NCT02807415).

PMID- 29327949
TI  - Work-exacerbated Asthma.

PMID- 29327950
TI  - Association of Avian Veterinarians News.

PMID- 29327951
TI  - What Is Your Diagnosis?

PMID- 29327953
TI  - Multicentric Cryptococcosis in a Congo African Grey Parrot ( Psittacus erithacus
      erithacus).
AB  - An approximately 10-year-old, female Congo African grey parrot ( Psittacus
      erithacus erithacus) developed progressive, unilateral exophthalmos and
      buphthalmos. Survey radiographs revealed a large, coelomic, soft tissue mass,
      which was confirmed on computed tomography scan. Aspirates of both the contents
      of the buphthalmic globe and coelomic mass were consistent with Cryptococcus
      species. Initial results were later confirmed with serum antigen latex
      agglutination and polymerase chain reaction testing, and the organism was then
      identified as Cryptococcus neoformans with DNA sequencing. During the course of 1
      year, the bird was treated with combinations of oral terbinafine, fluconazole,
      and flucytosine, as well as intraocular amphotericin B. The coelomic mass
      dramatically decreased in size during the course of treatment, but the globe
      continued to enlarge. The bird died after exhibiting ataxia and seizures
      approximately 13 months after initial diagnosis, and necropsy confirmed
      colonization of the cerebrum and meninges with Cryptococcus. Cryptococcus remains
      a rare fungal disease of birds that is often refractory to treatment.

PMID- 29327954
TI  - Prevalence of Caryospora Species (Apicomplexa: Eimeriidae) in Falcons in the
      United Arab Emirates.
AB  - A total of 3975 fecal samples, originated from the same number of individual
      birds, from 7 dedicated falcon hospitals, were examined to determine the
      prevalence of Caryospora species in the falcon population used in the sport of
      falconry in the United Arab Emirates (UAE). From that total, 297 (7.5%) were
      positive for the presence of Caryospora species. The falcons were all captive
      bred within the UAE and abroad, mainly from Germany, Spain, the United States,
      and Canada. Positive samples for the presence of Caryospora species were
      sporulated, and the taxonomy was established based on morphologic
      characteristics. The results showed the prevalence of the following Caryospora
      species: C kutzeri 41.4%, C neofalconis 25.6%, C megafalconis 18.2%, C falconis
      10.4%, C cherrughi 3.7%, and C boeri 0.7%. The prevalence of Caryospora species
      among the various falcon species in this study was: gyr * peregrine hybrid
      falcons ( Falco rusticolus * Falco peregrinus), 27.3%; gyr falcons ( Falco
      rusticolus), 25.6%; peregrine falcons ( Falco peregrinus), 20.5%; saker falcons (
      Falco cherrug), 16.5%; gyr * saker hybrid falcons ( Falco rusticolus * Falco
      cherrug), 8.1%; Eurasian kestrels ( Falco tinnunculus), 1%; red-napped shaheen (
      Falco pelegrinoides babylonicus), 0.7%; and American kestrels ( Falco
      sparverius), 0.3%.

PMID- 29327955
TI  - Co-occurrence of Mycoplasma Species and Pigeon Herpesvirus-1 Infection in Racing
      Pigeons ( Columba livia).
AB  - Oropharyngeal swab samples were collected from 438 live racing pigeons ( Columba
      livia), with and without signs of respiratory disease, that were housed in 220
      lofts in 3 provinces in the western part of the Netherlands. Polymerase chain
      reaction (PCR) was used to identify Mycoplasma species and pigeon herpesvirus-1
      (PHV-1) from the samples. In 8.6% of the pigeon lofts tested, signs of
      respiratory disease were present in pigeons at sampling, and in 30.9% of the
      sampled pigeon lofts, respiratory signs were observed in pigeons during the 6
      month period immediately before sampling. A total of 39.8% of tested pigeons
      (54.5% of tested lofts) were positive for Mycoplasma species, and 30.6% of tested
      pigeons (48.6% of tested lofts) were positive for PHV-1. In 15.8% of the tested
      pigeons (26.8% of tested pigeon lofts), coinfection by Mycoplasma species and PHV
      1 was identified. The number of pigeon lofts having pigeons coinfected by
      Mycoplasma species and PHV-1 was higher than that where only one of the
      infections was identified. Neither the presence of Mycoplasma species, PHV-1, nor
      the co-occurrence of both infections was significantly associated with signs of
      respiratory disease.

PMID- 29327956
TI  - The Incidence and Treatment Outcomes of Macrorhabdus ornithogaster Infection in
      Budgerigars ( Melopsittacus undulatus) in a Veterinary Clinic.
AB  - Macrorhabdus ornithogaster, avian gastric yeast, is a common cause of
      gastrointestinal disease in budgerigars ( Melopsittacus undulatus). To better
      understand the clinical disease in budgerigars presented in a practice
      population, we reviewed the occurrence, clinical signs, and treatment success of
      M ornithogaster disease in budgerigars during a 2.5-year period at the Clinic for
      Birds and Reptiles, University of Leipzig (Leipzig, Germany). The yeast was
      diagnosed by microscopic examination of fresh fecal samples. Male budgerigars of
      all ages were most affected. Most clinical signs in birds with confirmed positive
      results were nonspecific, except for the occurrence of undigested seeds in the
      feces. Although radiographic appearance of a dilated proventriculus is indicative
      of a M ornithogaster infection, it is difficult to recognize because of the small
      size of the budgerigars. Birds with positive results were treated with
      amphotericin B (100 mg/kg PO q12h) for 4 weeks. Treatment was stressful for the
      birds because of the handling required and the long treatment duration, and
      therapeutic results were unsatisfactory. Therefore, the indications for treatment
      with amphotericin B should be carefully considered in birds with positive M
      ornithogaster results. An increased occurrence of the infection in association
      with other pathogens was detected.

PMID- 29327957
TI  - Unusual Outbreak of Fatal Clostridiosis in a Group of Captive Brown Pelicans (
      Pelecanus occidentalis).
AB  - Fatal clostridial infections and clostridial toxicoses are common in birds. Most
      fatalities are associated with toxin production and progress rapidly, often
      within 24 hours of infection. We describe an unusual and protracted course of
      disease in 6 captive brown pelicans ( Pelecanus occidentalis), which was believed
      to result from toxicosis by toxovar A produced by a mixed infection with
      Clostridium sordellii and Clostridium perfringens. Although the first death in
      the group occurred 3 days after signs of illness were documented, the remaining
      birds died over a 38-day period despite aggressive antibiotic and supportive
      therapy. Although the birds presented with classic signs of botulism, Clostridium
      botulinum was not identified in any tissues or environmental samples. Postmortem
      findings in all pelicans included extensive subacute myonecrosis, enteritis, and
      nonsuppurative hepatitis. Alpha-toxins and sordellilysin genes from C perfringens
      and C sordelli isolates, respectively, were detected via polymerase chain
      reaction. The source of the pathogenic bacteria was sediment within a water basin
      inside the affected birds' enclosure.

PMID- 29327958
TI  - How Not to "Wing It" with Backyard Poultry.

PMID- 29327960
TI  - Pharmacokinetics of a Single Intramuscular Injection of Long-Acting Ceftiofur
      Crystalline-Free Acid in Cattle Egrets ( Bubulcus ibis).
AB  - We determined the pharmacokinetic properties of ceftiofur crystalline-free acid
      (CCFA), a long-acting antibiotic, after a single intramuscular injection in
      cattle egrets ( Bubulcus ibis). A dose of 20 mg/kg was administered
      intramuscularly to 18 birds and blood samples were collected via jugular
      venipuncture at 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, and 240
      hours after CCFA administration. Plasma concentrations of ceftiofur free acid
      equivalents (CFAEs) were measured via high-performance liquid chromatography. The
      minimum inhibitory concentration (MIC) of 1 MUg/mL was reached by 1 hour after
      administration and remained higher than the MIC for at least 72 hours in all
      birds. This target concentration is effective for many bacterial infections in
      avian species. The area under the plasma concentration versus time curve was
      451.3 h*MUg/mL, maximum plasma concentration was 16.22 MUg/mL, time to maximum
      plasma concentration was 3.2 hours, mean harmonic half-life was 37.92 hours, and
      time that the concentrations of CFAEs were higher than the target MIC was a
      minimum of 72 hours.

PMID- 29327961
TI  - Tracheal Resection in a Secretary Bird ( Sagittarius serpentarius) with
      Granulomatous, Foreign-body Induced Tracheitis.
AB  - A 24-year-old female secretary bird ( Sagittarius serpentarius) was presented
      with acute, mild dyspnea occurring only during feeding times. Despite initial
      conservative therapy consisting of antibiotics and antifungal, antiparasitic, and
      anti-inflammatory drugs, the dyspnea worsened progressively, resulting in severe
      respiratory distress. Radiographs of the trachea suggested stenosis in the caudal
      one-third of the trachea. Tracheal endoscopy revealed an obstruction of
      approximately 90% of the tracheal lumen, in addition to mild suspected
      aspergillosis of the air sacs. Tracheal resection and anastomosis were performed,
      during which 1.5 cm of abnormal trachea was removed. Histopathologic examination
      showed severe granulomatous tracheitis, most likely induced by foreign body
      material. Respiratory signs resolved immediately postoperatively. Antibiotic and
      anti-inflammatory therapy continued for another 7 days and the bird was treated
      with antifungals for a total of 45 days. The bird recovered uneventfully. We
      encourage tracheal resection and anastomosis for severe tracheal stenosis even in
      aged, large birds of prey that are managed in large aviaries.

PMID- 29327962
TI  - Acute, Fatal, Presumptive Xylitol Toxicosis in Cape Sugarbirds ( Promerops
      cafer).
AB  - Twenty-nine wild Cape sugarbirds ( Promerops cafer) died acutely after ingestion
      of a homemade xylitol nectar solution from a bird feeder. The most aggressive
      feeders were first affected. Most birds showed clinical signs within 15 minutes
      of nectar ingestion, including incoordination, weakness, falling from perches,
      collapse, and death. A few birds showing clinical signs seemed to spontaneously
      recover and fly away. Full necropsy examinations done on 27 birds were hampered
      by freezing artifact and autolysis, but results indicated death was caused by the
      consequences of acute hypoglycemia. A presumptive diagnosis of xylitol toxicity
      was made based on the history, clinical signs, and absence of other obvious
      causes of death. This is potentially the first record of xylitol toxicity in wild
      birds.

PMID- 29327963
TI  - Antemortem Diagnosis of Coxiellosis in a Blue and Gold Macaw ( Ara ararauna).
AB  - A 15-year-old female blue and gold macaw ( Ara ararauna) was presented for
      evaluation after being found laterally recumbent, reluctant to move, and
      lethargic. Results of a complete blood count showed an increased number of
      immature heterophils with increased cytoplasmic basophilia and degranulation and
      the presence of a left shift. Radiographs and a computed tomography scan were
      performed and revealed a markedly enlarged spleen. An ultrasound-guided fine
      needle aspirate of the spleen was submitted for cytologic examination and aerobic
      bacterial culture. While the culture revealed no growth, cytologic examination
      identified mononuclear phagocytes with cytoplasmic vacuoles containing structures
      consistent with bacteria. Pan-bacterial 16S rRNA polymerase chain reaction of the
      splenic sample followed by direct sequencing identified a Coxiella-like agent
      identical to one previously isolated in the liver of a golden-mantled rosella (
      Platycercus eximius). Phylogenetic analysis shows that avian coxiellosis agents
      and Coxiella burnetii, the agent of Q fever, represent 2 independent events of
      development of vertebrate pathogenicity in this group of tick endosymbionts. This
      report suggests diagnostic and treatment directions for coxiellosis in avian
      patients and indicates where further study is needed.

PMID- 29327964
TI  - Endoscopic Removal of Gastrointestinal Foreign Bodies in Two African Grey Parrots
      ( Psittacus erithacus) and a Hyacinth Macaw ( Anodorhynchus hyacinthinus).
AB  - Two African grey parrots ( Psittacus erithacus) and one hyacinth macaw (
      Anodorhynchus hyacinthinus) were examined because of varying clinical signs
      ranging from general lethargy to seizure-like episodes and regurgitation.
      Radiography and fluoroscopy in the 3 birds demonstrated variable degrees of
      gastric abnormalities, suggesting the presence of foreign material or stricture
      like defects. Upper gastrointestinal rigid endoscopy by ingluviotomy revealed
      foreign bodies that were removed endoscopically. Minor postoperative
      complications were pulmonary congestion or mild aspiration and cardiac
      arrhythmia, both of which resolved, and no serious deleterious effects were
      associated with endoscopy in the short or long term. Endoscopy is recommended for
      examination and removal of foreign bodies from the upper gastrointestinal tract
      because it is less invasive and traumatic than traditional surgical approaches.

PMID- 29327966
TI  - Ocular Histomorphometry of Free-Living Common Kestrels ( Falco tinnunculus).
AB  - We evaluated the histomorphometry of the eye structures (cornea, retina, choroid,
      and sclera) of 13 adult free-living common kestrels ( Falco tinnunculus). Birds
      included in the study were euthanatized because of severe trauma from a motor
      vehicle injury. The eyes were enucleated immediately after euthanasia, fixed in
      10% buffered formalin, and decalcified. The right eyes were cut vertically
      (dorsoventrally) and the left eyes cut horizontally (temporonasally). Tissues
      were processed, stained with hematoxylin and eosin, and evaluated by an image
      analysis software. The thicknesses of the diverse corneal layers were measured at
      3 points; 2 at the peripheral region (A and C) and one at the central region (B).
      The thicknesses of the retina, choroid, and sclera were evaluated at 6 different
      positions. Measurements of the left and right eyes of the male and female birds
      were compared. The median thicknesses of the cornea at the peripheral points were
      210.78 (A) and 197.79 (C) MUm, and 129 MUm at the central point (B). The
      thickness of the cornea did not differ significantly between males and females or
      between right or left eyes. The mean thicknesses of the retina, choroid, and
      sclera were 91.13, 20.74, and 92.8 MUm, respectively. The thickness of the
      choroid and sclera did not differ significantly between the sexes or between the
      right and left eyeballs. The retinas of the females were significantly thicker
      than those of males at the points in the fundus of the eyeball, near the
      insertion of the pecten (optical nerves).

PMID- 29327967
TI  - Cumulative Subject Index.

PMID- 29327969
TI  - AtOZF1 Positively Regulates Defense Against Bacterial Pathogens and NPR1
      Independent Salicylic Acid Signaling.
AB  - Plant hormone salicylic acid (SA) plays critical roles in defense signaling
      against biotrophic pathogens. Pathogen inoculation leads to SA accumulation in
      plants. SA activates a transactivator protein NPR1, which, in turn,
      transcriptionally activates many defense response genes. Reports also suggest the
      presence of NPR1-independent pathways for SA signaling in Arabidopsis. Here, we
      report the characterization of a zinc-finger protein-coding gene AtOZF1 that
      positively influences NPR1-independent SA signaling. Mutants of AtOZF1 are
      compromised, whereas AtOZF1-overexpressing plants are hyperactive for defense
      against virulent and avirulent pathogens. AtOZF1 expression is SA-inducible.
      AtOZF1 function is not required for pathogenesis-associated biosynthesis and
      accumulation of SA. However, it is required for SA responsiveness. By generating
      atozf1npr1 double mutant, we show that contributions of these two genes are
      additive in terms of defense. We identified AtOZF1-interacting proteins by a
      yeast-two-hybrid screening of an Arabidopsis cDNA library. VDAC2 and NHL3 are two
      AtOZF1-interacting proteins, which are positive regulators of basal defense.
      AtOZF1 interacts with NHL3 and VDAC2 in plasma membrane and mitochondria,
      respectively. Our results demonstrate that AtOZF1 coordinates multiple steps of
      plant-pathogen interaction.

PMID- 29327970
TI  - It is Electric! Electroconvulsive Therapy for Refractory Central Pain and
      Comorbid Psychiatric Disease.
AB  - Central pain syndromes are a complex, diverse group of clinical conditions that
      are poorly understood. We present a patient with progressive, debilitating
      central pain and co-existing mood disorders that was refractory to multimodal
      pharmacologic and nonpharmacologic therapies, but that ultimately responded to
      electroconvulsive therapy (ECT). The patient described it at various times as her
      skin being "lit on fire," "stabbed," "squeezed like a boa constrictor," or
      itching unbearably. She underwent a course of three sequential ECT treatments
      during her hospitalization and it dramatically decreased her pain. She began
      maintenance ECT, and a rate of roughly one treatment a month provided persistent
      pain suppression. Despite this lack of evidence, ECT has a favorable safety
      profile and can be considered in the therapeutic armamentarium for patients who
      have exhausted standard treatment regimens who continue to have suffering in the
      setting of central pain syndromes and coexisting mood disorders.

PMID- 29327971
TI  - Inflammatory Potential of Diet is Associated with Increased Odds of Cataract in a
      Case-Control Study from Iran.
AB  - BACKGROUND: In previous studies, diet has been shown to be associated with
      cataract. However, no study to date has focused on the association between
      inflammatory potential of diet and cataract. OBJECTIVES: In this case-control
      study conducted in Iran, we examined the association of the dietary inflammatory
      index (DII(r)) and cataract. METHODS: This case-control study included 97
      cataract cases and 198 healthy controls hospitalized for acute non-neoplastic
      diseases with the control group matched according to age (with a five-year
      interval) and sex with the case group. The DII was computed based on dietary
      intake assessed by a previously validated food frequency questionnaire.
      Multivariable logistic regression models were used to estimate odds ratios (ORs),
      with the DII analyzed as both continuous and as tertiles. Energy was adjusted
      using the residual method. RESULTS: Subjects with higher DII scores (i.e., with a
      more pro-inflammatory diet) had a higher odds of cataract, with the DII being
      used as both a continuous variable (ORcontinuous 1.51, 95% confidence interval,
      CI, 1.13 - 2.03; one unit increase corresponding to ~18% of its range in the
      current study) and as tertiles (ORtertile3vs1 2.67, 95%CI 1.32 - 5.48, Ptrend =
      0.002). CONCLUSIONS: These results indicate that a pro-inflammatory diet is
      associated with increased risk of cataract. Additional studies should be
      conducted to further explore this association.

PMID- 29327972
TI  - Albert Dereymaeker and Joseph Cyriel Mulier's description of anterior cervical
      discectomy with fusion in 1955.
AB  - Anterior cervical discectomy with fusion (ACDF) is a very well-known and often
      performed procedure in the practice of spine surgeons. The earliest descriptions
      of the technique have always been attributed to Cloward, Smith, and Robinson.
      However, in the French literature, this procedure was also described by others
      during the exact same time period (in the 1950s). At a meeting in Paris in 1955,
      Belgians Albert Dereymaeker and Joseph Cyriel Mulier, a neurosurgeon and an
      orthopedic surgeon, respectively, described the technique that involved an
      anterior cervical discectomy and the placement of an iliac crest graft in the
      intervertebral disc space. In 1956, a summary of their oral presentation was
      published, and a subsequent paper-an illustrated description of the technique and
      the details of a larger case series with a 3.5-year follow-up period-followed in
      1958. The list of authors who first described ACDF should be completed by adding
      Dereymaeker's and Mulier's names. They made an important contribution to the
      practice of spinal surgery that was not generally known because they published in
      French.

PMID- 29327973
TI  - Fluoroscopy-guided percutaneous vertebroplasty for symptomatic loosened pedicle
      screw and instrumentation-associated vertebral fracture: an evaluation of initial
      experiences and technical note.
AB  - OBJECTIVE For symptomatic loosened pedicle screws and instrumentation-associated
      vertebral fracture, extensive surgery to remove the pedicle screws and extend the
      instrumentation, along with the reinsertion of more pedicle screws, is usually
      the treatment of choice. After such a surgery, however, similar complications
      will still be encountered. In this study the authors propose minimally invasive
      percutaneous cement augmentation under fluoroscopic guidance as a salvage
      procedure that eliminates the inherent risks of conventional extensive surgery.
      METHODS The records for 10 consecutive patients who had undergone fluoroscopy
      guided percutaneous cement augmentation for loosened pedicle screws and
      instrumentation-associated vertebral fractures were reviewed. The procedures,
      performed with the patients under local anesthesia, were basically similar to
      vertebroplasty except for the preexisting pedicle screws. The trocar was inserted
      under fluoroscopic guidance, along the path of the loosened pedicle screw, using
      the latero-pedicular approach. The visual analog scale (VAS) and radiographic
      images were used for clinical outcome assessment at 3, 6, and 12 months after
      surgery. RESULTS The mean follow-up period was 14.3 months. The mean
      postoperative hospital stay was 1.2 days. There was neither cement leakage into
      the posterior neuroforamen nor neurological complication in this series. The mean
      VAS score improved from 5.9 preoperatively to 2.5 at the last follow-up (p =
      0.02). Eight patients obtained satisfactory results and 2 needed revision open
      surgery. CONCLUSIONS The results demonstrate that minimally invasive fluoroscopy
      guided percutaneous vertebroplasty is technically feasible and can be performed
      safely and effectively for symptomatic loosened pedicle screws and
      instrumentation-associated vertebral fracture.

PMID- 29327974
TI  - The FDA and the US direct-to-consumer marketplace for stem cell interventions: a
      temporal analysis.
AB  - Hundreds of businesses in the US currently advertise a wide range of non-US FDA
      approved stem cell interventions. Here we present a novel systematic temporal
      analysis of US companies engaged in direct-to-consumer marketing of putative stem
      cell treatments. Between 2009 and 2014, the number of new US stem cell businesses
      with websites grew rapidly, at least doubling on average every year. From 2014 to
      2016, approximately 90-100 new stem cell business websites appeared per year. In
      contrast, from 2012 to the present, regulatory activity in the form of FDA
      warning letters has been limited. These data point to a problematic disconnect
      between a rapidly expanding US direct-to-consumer stem cell industry and limited
      FDA oversight of this marketplace. More consistent, timely and effective FDA
      actions are urgently needed.

PMID- 29327975
TI  - Impact of CYP2D6 on venlafaxine metabolism in Trinidadian patients with major
      depressive disorder.
AB  - AIM: This study aimed to assess the impact of CYP2D6 and CYP2C19 variation on
      venlafaxine (VEN) at steady state in patients from Trinidad and Tobago of Indian
      and African descent with major depressive disorder. PATIENTS & METHODS: Patients
      were phenotyped with dextromethorphan, genotyped for CYP2D6 and CYP2C19, and
      metabolic ratios for VEN obtained at 2-week intervals. RESULTS: Of 61 patients,
      55 were genotyped and phenotyped and 47 completed 8 weeks of VEN treatment. The
      majority of patients had metabolic ratios for VEN that were consistent with those
      for dextromethorphan and genotype-predicted phenotype using activity scores. One
      subject presented with a novel no-function allele, CYP2D6*99. No correlations
      were observed with CYP2C19 genotype. CONCLUSION: CYP2D6 genotype analysis
      provides valuable information to individualize drug therapy with VEN.

PMID- 29327976
TI  - Endoscopic Treatment of Transesophageal Echocardiography-Induced Esophageal
      Perforation.
AB  - BACKGROUND: Perforation of the esophagus is the most severe complication of
      transesophageal echocardiography (TEE) and can lead to mediastinitis, pleural
      empyema, or peritonitis. Currently, the majority of patients receive operative
      treatment with only 6% treated endoscopically. We report our experience with
      endoscopic and conservative approaches. METHODS: We retrospectively reviewed all
      patients treated for esophageal perforation and included all patients with
      perforation caused by TEE. All patients with perforation of the esophagus by TEE
      probe underwent conservative or endoscopic treatment, drainage of pleural and
      mediastinal retentions, and adjusted to antibiotic therapy. RESULTS: From January
      2004 to December 2014 a total of 109 patients were treated for esophageal
      perforation in our department. In 6 patients (5.5%) the perforation was caused by
      TEE. Location was cervical and midthoracic in 2 and 4 cases, respectively. All
      patients underwent successful endoscopic treatment and no further surgical
      procedure, such as esophageal suture or resection was necessary. The mean time
      between TEE and therapy of the perforation was 7.3 days. In all patients closure
      of the leakage could be achieved within 30 days. Mortality rate was 0%.
      CONCLUSIONS: Esophageal perforations caused by TEE are typically small, in the
      cervical and mid esophagus, and minimally contaminated. These are good prognostic
      factors for successful endoscopic treatment with preservation of the esophagus.
      Operative treatment should only be considered in cases of failed endoscopic
      treatment.

PMID- 29327977
TI  - Status and Challenges of Predicting and Diagnosing Sepsis in Burn Patients.
AB  - Burns are a common form of trauma that account for more than 300,000 deaths each
      year worldwide. Survival rates have improved over the past decades because of
      improvements in nutritional and fluid support, burn wound care, and infection
      control practices. Death, however, remains unacceptably high. The primary cause
      of death has changed over the last decades from anoxic causes to now
      predominantly infections and sepsis. Sepsis and septic complications are not only
      major contributors to poor outcomes, but they further result in longer hospital
      stay and higher healthcare costs. Despite the importance of infections and
      sepsis, the diagnosis and prediction remain a major challenge. To date, no clear
      diagnostic criteria or predictive formula exist that can predict reliably the
      occurrence of sepsis and infections. This review will highlight and discuss
      current definitions and criteria for diagnosis as well as predictive biomarkers
      of sepsis in patients with burns. It will also present the diagnostic tools
      employed, such as procalcitonin, C-reactive protein, and cytokines. We will
      discuss the benefits and shortcomings of different treatment modalities in the
      context of sepsis prevention. Last, we identify new therapeutic strategies for
      sepsis prediction and present future considerations to prevent sepsis in patients
      with burns. Minimizing and preventing septic complications through early
      detection would significantly benefit patients and necessitate continued research
      to unravel new biomarkers and mechanisms. Subsequent studies need to take a fresh
      perspective and consider the implementation of patient-centered therapeutic
      strategies.

PMID- 29327978
TI  - In Vivo CYP3A Activity in Palliative Care Patients: Study Protocol for a Single
      Arm Prospective Trial.
AB  - BACKGROUND: Drug interactions are a common cause for escalation of debilitating
      symptoms in palliative care patients. CYP3A is the most relevant CYP enzyme in
      humans involved in metabolism of about half of all available pharmaceuticals.
      OBJECTIVE: To increase knowledge about the CYP3A enzyme and the impact of drug
      interactions on its activity to improve dosing in palliative care patients.
      DESIGN: The prospective clinical trial uses a secure method of analyzing CYP3A
      activity in humans: Administration of a marker substance followed by the
      determination of its blood concentrations as well as the concentrations of its
      metabolite at certain points of time and corresponding metabolic clearance
      calculations. SETTING: The ongoing trial is carried out at a palliative care unit
      under real-life clinical conditions. MEASUREMENTS: A four-hour pharmacokinetic
      profile after oral administration of the marker substance (microdose of
      midazolam) will be obtained from each enrolled patient. Plasma concentrations of
      midazolam and its primary metabolite will be quantified by mass spectrometry
      techniques. CYP3A activity will be calculated as partial metabolic clearance from
      a limited sampling area under the curve. All other drugs taken by the
      participating patients will be considered as well as recent blood test results
      and the patients' diagnoses. CONCLUSIONS: This is the first prospective study
      dealing with drug metabolism in patients on a palliative care unit. The trial is
      based on reliable and established methods aiming to provide improved dosing
      regimens and thus optimize pharmacological therapies in this specialty.

PMID- 29327979
TI  - The General Motor Ability Hypothesis: An Old Idea Revisited.
AB  - While specific motor abilities have become a popular explanation for motor
      performance, the older, alternate notion of a general motor ability should be
      revisited. Current theories lack consensus, and most motor assessment tools
      continue to derive a single composite score to represent motor capacity. In
      addition, results from elegant statistical procedures such as higher order factor
      analyses, cluster analyses, and Item Response Theory support a more global motor
      ability. We propose a contemporary model of general motor ability as a
      unidimensional construct that is emergent and fluid over an individual's
      lifespan, influenced by both biological and environmental factors. In this
      article, we address the implications of this model for theory, practice,
      assessment, and research. Based on our hypothesis and Item Response Theory, our
      Lifespan Motor Ability Scale can identify motor assessment tasks that are
      relevant and important across varied phases of lifespan development.

PMID- 29327980
TI  - Effects of Endoscopic Thoracic Sympathectomy on Raynaud's Disease.
AB  - INTRODUCTION: Raynaud's disease is a disorder that is characterized by attacks of
      pain, cyanosis, redness, and numbness in the upper extremities caused by
      vasospasm of digital arteries due to cold or emotional stress. We aimed at
      demonstrating our experiences with endoscopic thoracic sympathectomy (ETS) in the
      treatment of Raynaud's disease. METHODS: From 48 patients who underwent ETS for
      various reasons at our department between January 2014 and January 2015, we
      reviewed 9 patients with Raynaud's disease (18.7%) with respect to their
      demographic characteristics such as gender and age, postoperative complications,
      short-term results, side effects, recurrence of symptoms, and long-terms results.
      RESULTS: The symptoms and findings reappeared and the number and dosage of the
      drugs used returned to their preoperative levels in 66.6% of the patients at
      month 6, and in all patients except 1 at the end of the 1st year. CONCLUSION: ETS
      should be considered an ultimate choice for patients with Raynaud's disease who
      have treatment-resistant severe symptoms and serious complications, disturbed
      social and daily lives, and impaired quality of life, and all patients should be
      properly informed before the surgery about the possibility of a high rate of
      recurrence.

PMID- 29327982
TI  - Communicating Your Research with Social Media: A Practical Guide to Using Blogs,
      Podcasts, Data Visualisations and Video, by Amy Mollett, Cheryl Brumley, Chris
      Gilson, and Sierra Williams.

PMID- 29327981
TI  - HIV/AIDS Outreach: Curriculum Development and Skills Training to Health and
      Information Professionals.
AB  - With funding from the National Library of Medicine HIV/AIDS Community Information
      Outreach Program (ACIOP), librarians at the University of Florida Health Sciences
      Libraries partnered with university and community groups to facilitate
      collaboration, develop new information resources, develop information-seeking
      skills, and raise general awareness surrounding HIV/AIDS risks, prevention, and
      treatment. This article describes the skills development elements of the project,
      including development and implementation of an HIV/AIDS information resource
      curriculum for health care providers, social services professionals, and public
      librarians within the project's partner organizations.

PMID- 29327984
TI  - Taking the Pulse of the University of Tennessee Medical Center's Health Literacy
      Knowledge.
AB  - Low health literacy is well documented in East Tennessee. Before addressing the
      issue, librarians at the Preston Medical Library, University of Tennessee Medical
      Center in Knoxville, Tennessee, conducted a needs assessment of hospital staff to
      determine their knowledge of health literacy and the need for training. As a
      follow-up, library staff conducted training sessions for nurses through classes,
      small group meetings, and staff huddles. The result is an increased dialogue of
      health literacy at the hospital, along with new research projects, a forum, and a
      summit meeting.

PMID- 29327983
TI  - Serving Community Faculty Through a Dedicated Liaison.
AB  - Community-based medical schools rely heavily on volunteer faculty to provide
      medical education. Volunteer faculty consist of health care professionals,
      primarily physicians, who commit to educating medical students and residents.
      While these volunteer faculty are typically unpaid, many medical schools provide
      some benefits to them for volunteering their time. One such benefit, although
      rarely noted in library or medical education literature, is access to academic
      medical library resources and services. This article highlights a library
      services liaison model dedicated to the support of volunteer faculty at a
      community-based medical school.

PMID- 29327985
TI  - Effective Difficult Conversations: A Step-By-Step Guide, by Catherine B. Soehner
      and Ann Darling.

PMID- 29327986
TI  - Marketing for Special and Academic Libraries: A Planning and Sourcebook, by
      Valerie S. Gordon and Patricia C. Higginbottom.

PMID- 29327987
TI  - OSTMED.DR(r), an Osteopathic Medicine Digital Library.
AB  - The OSTMED.DR(r) database provides access to both citation and full-text
      osteopathic literature, including the Journal of the American Osteopathic
      Association. Currently, it is a free database searchable using basic and advanced
      search features.

PMID- 29327988
TI  - Alexa, Siri, Cortana, and More: An Introduction to Voice Assistants.
AB  - Voice assistants are software agents that can interpret human speech and respond
      via synthesized voices. Apple's Siri, Amazon's Alexa, Microsoft's Cortana, and
      Google's Assistant are the most popular voice assistants and are embedded in
      smartphones or dedicated home speakers. Users can ask their assistants questions,
      control home automation devices and media playback via voice, and manage other
      basic tasks such as email, to-do lists, and calendars with verbal commands. This
      column will explore the basic workings and common features of today's voice
      assistants. It will also discuss some of the privacy and security issues inherent
      to voice assistants and some potential future uses for these devices. As voice
      assistants become more widely used, librarians will want to be familiar with
      their operation and perhaps consider them as a means to deliver library services
      and materials.

PMID- 29327989
TI  - Making It Work for Everyone: An Evolving Reference Service.
AB  - At an academic health science center, librarians identified problems, weaknesses,
      and strengths in reference services. The on-call reference schedule was
      discontinued and a question flowchart was developed for circulation staff. Only
      research questions were referred to librarians, who would respond if available.
      Circulation staff perceived the unscheduled, voluntary model was not working well
      for the patrons or the staff. After two months, the schedule was reinstated with
      a hybrid version of the previous on-call format. In the process of changing the
      service model, the library staff also underwent a cultural change.

PMID- 29327991
TI  - A Clinical Librarian Embedded in Medical Education: Patient-Centered Encounters
      for Preclinical Medical Students.
AB  - Adding patient encounters and simulation to the preclinical years of medical
      school is becoming increasingly popular. This article describes the creation of
      active learning opportunities by a clinical librarian that are aimed at training
      preclinical students through the use of simulated patient scenarios. Scenarios
      for second-year students walk them through the evidence-based resources needed in
      clinical years and beyond through a standardized patient encounter. Scenarios for
      first-year students involve role-play of cases where the patient and physician
      bring contrasting ideas to the outpatient interaction. All scenarios are carried
      out under the guidance of a clinician and librarian.

PMID- 29327992
TI  - DigitalHub: A Repository Focused on the Future.
AB  - The DigitalHub scholarly repository was developed and launched at the Galter
      Health Sciences Library for the Feinberg School of Medicine and the greater
      Northwestern Medicine community. The repository was designed to allow scholars
      the ability to create, share, and preserve a range of citable digital outputs.
      This article traces the evolution of DigitalHub's development and engagement
      activities, highlighting project challenges, innovations, success stories, and
      the team-based approach that was employed to successfully achieve project goals.

PMID- 29327993
TI  - Managing a Biomedical Library's Instruction Program: Redefining Scope.
AB  - The National Institutes of Health (NIH) library instruction program provides
      training services to staff, clinicians, and researchers across NIH and several
      Department of Health and Human Services (HHS) operating divisions. The audience,
      training needs, and training topics are diverse and constantly changing. The NIH
      library has developed several new services and class topics to meet the needs of
      its NIH and HHS communities. Context, strategies, and future directions for the
      NIH library instruction program are described.

PMID- 29327994
TI  - The Medical Library Association Guide to Data Management for Librarians, edited
      by Lisa Federer.

PMID- 29327996
TI  - Letter to the Editor. Tumors of the fourth ventricle.

PMID- 29327995
TI  - The Impact of Library Tutorials on the Information Literacy Skills of
      Occupational Therapy and Physical Therapy Students in an Evidence-Based Practice
      Course: A Rubric Assessment.
AB  - This study measures how online library instructional tutorials implemented into
      an evidence-based practice course have impacted the information literacy skills
      of occupational and physical therapy graduate students. Through a rubric
      assessment of final course papers, this study compares differences in students'
      search strategies and cited sources pre- and post-implementation of the
      tutorials. The population includes 180 randomly selected graduate students from
      before and after the library tutorials were introduced into the course
      curriculum. Results indicate a statistically significant increase in components
      of students' searching skills and ability to find higher levels of evidence after
      completing the library tutorials.

PMID- 29327997
TI  - Mechanical thrombectomy in basilar artery occlusion: influence of reperfusion on
      clinical outcome and impact of the first-line strategy (ADAPT vs stent
      retriever).
AB  - OBJECTIVE Several randomized trials have been focused on patients with anterior
      circulation stroke, whereas few data on posterior circulation stroke are
      available. Thus, new mechanical thrombectomy (MT) strategies, including a direct
      aspiration first-pass technique (ADAPT), remain to be evaluated in basilar artery
      occlusion (BAO) patients. The authors here assessed the influence of reperfusion
      on outcome in BAO patients and examined whether ADAPT improves the reperfusion
      rate compared with stent retriever devices. METHODS Three comprehensive stroke
      centers prospectively collected individual data from BAO patients treated with
      MT. Baseline characteristics as well as radiographic and clinical outcomes were
      compared between the 2 MT strategies. The primary outcome measure was the rate of
      successful reperfusion, defined as a modified Thrombolysis in Cerebral Infarction
      (mTICI) grade of 2b-3. Favorable outcome was defined as a 90-day modified Rankin
      Scale score of 0-2. RESULTS Among the 100 adult patients included in the study,
      46 were treated with first-line ADAPT (median age 61 years, IQR 53-71 years;
      stent-retriever rescue therapy was secondarily used in 12 [26.1%]) and 54 were
      treated with a primary stent retriever (median age 67 years, IQR 53-78 years).
      There was no difference in baseline characteristics between the 2 treatment
      groups, except for the rate of diabetes (19.6% vs 5.7%, respectively, p = 0.035).
      Successful reperfusion was achieved in 79% of the overall study sample. Overall,
      the rate of favorable outcome was 36.8% and 90-day all-cause mortality was 44.2%.
      Successful reperfusion positively impacted favorable outcome (OR 4.57, 95% CI
      1.24-16.87, p = 0.023). A nonsignificant trend toward a higher successful
      reperfusion rate (unadjusted OR 2.56, 95% CI 0.90-7.29, p = 0.071) and a
      significantly higher rate of complete reperfusion (mTICI grade 3; unadjusted OR
      2.59, 95% CI 1.14-5.86, p = 0.021) was found in the ADAPT group. The procedure
      duration was also significantly lower in the ADAPT group (median 45 minutes, IQR
      34 to 62 minutes vs 56 minutes, IQR 40 to 90 minutes; p = 0.05), as was the rate
      of periprocedural complications (4.3% vs 25.9%, p = 0.003). Symptomatic
      intracranial hemorrhage (0.0% vs 4.0%, p = 0.51) and 90-day all-cause mortality
      (46.7% vs 42.0%, p = 0.65) were similar in the 2 groups. CONCLUSIONS Among BAO
      patients, successful reperfusion is a strong predictor of a 90-day favorable
      outcome, and the choice of ADAPT as the first-line strategy achieves a
      significantly higher rate of complete reperfusion with a shorter procedure
      duration.

PMID- 29327998
TI  - A novel scale for describing visual outcomes in patients following resection of
      lesions affecting the optic apparatus: the Unified Visual Function Scale.
AB  - OBJECTIVE Historically, descriptions of visual acuity and visual field change
      following intracranial procedures have been very rudimentary. Clinicians and
      researchers have often used basic descriptions, such as "improved," "worsened,"
      and "unchanged," to describe outcomes following resections of tumors affecting
      the optic apparatus. These descriptors are vague, difficult to quantify, and
      challenging to apply in a clinical perspective. Several groups have attempted to
      combine visual acuity and visual fields into a single assessment score, but these
      are not user-friendly. The authors present a novel way to describe a patient's
      visual function as a combination of visual acuity and visual field assessment
      that is simple to use and can be used by surgeons and researchers to gauge visual
      outcomes following tumor resection. METHODS Visual acuity and visual fields were
      combined into 3 categories designed around the definitions of legal blindness and
      fitness to drive in Canada. The authors then applied the scale (the Unified
      Visual Function Scale, or UVFS) to their previously published case series of
      perisellar meningiomas to document and test overall visual outcomes for patients
      undergoing tumor resection. The results were compared with previously documented
      visual loss scales in the literature. RESULTS Using the UVFS the authors were
      able to capture the overall visual change; the scale was sensitive enough to
      define the overall visual improvement or worsening quantitatively, using
      categories that are clinically relevant and understandable. CONCLUSIONS The UVFS
      is a robust way to assess a patient's vision, combining visual fields and acuity.
      The implementation of pre- and postoperative assessment is sensitive enough to
      assess overall change while also providing clinically relevant information for
      surgeons, and allows for comparisons between treatment groups.

PMID- 29327999
TI  - Declining complication rates with flow diversion of anterior circulation
      aneurysms after introduction of the Pipeline Flex: analysis of a single
      institution series of 568 cases.
AB  - OBJECTIVE The second-generation Pipeline embolization device (PED), Flex, has
      several design upgrades, including improved opening and the ability to be
      resheathed, in comparison with the original device (PED classic). The authors
      hypothesized that Flex is associated with a lower rate of major complications.
      METHODS A prospective, IRB-approved, single-institution database was analyzed for
      all patients with anterior circulation aneurysms treated by flow diversion. The
      PED classic was used from August 2011 to January 2015, and the Pipeline Flex has
      been used since February 2015. RESULTS A total of 568 PED procedures (252 classic
      and 316 Flex) were performed for anterior circulation aneurysms. The average
      aneurysm size was 6.8 mm. Patients undergoing treatment with the Flex device had
      smaller aneurysms (p = 0.006) and were more likely to have undergone previous
      treatments (p = 0.001). Most aneurysms originated along the internal carotid
      artery (89% classic and 75% Flex) but there were more anterior cerebral artery
      (18%) and middle cerebral artery (7%) deployments with Flex (p = 0.001).
      Procedural success was achieved in 96% of classic and 98% of Flex cases (p =
      0.078). Major morbidity or death occurred in 3.5% of cases overall: 5.6% of
      classic cases, and 1.9% of Flex cases (p = 0.019). On multivariate logistic
      regression, predictors of major complications were in situ thrombosis (OR 4.3, p
      = 0.006), classic as opposed to Flex device (OR 3.7, p = 0.008), and device
      deployment in the anterior cerebral artery or middle cerebral artery as opposed
      to the internal carotid artery (OR 3.5, p = 0.034). CONCLUSIONS Flow diversion of
      anterior circulation cerebral aneurysms is associated with an overall low rate of
      major complications. The complication rate is significantly lower since the
      introduction of the second-generation PED (Flex).

PMID- 29328000
TI  - Conscious sedation with dexmedetomidine compared with asleep-awake-asleep
      craniotomies in glioma surgery: an analysis of 180 patients.
AB  - OBJECTIVE Awake craniotomies have become a feasible tool over time to treat brain
      tumors located in eloquent regions. Different techniques have been applied in
      neurooncology centers. Both "asleep-awake-asleep" (asleep) and "conscious
      sedation" were used subsequently at the authors' neurosurgical department. Since
      2013, the authors have only performed conscious sedation surgeries, predominantly
      using the alpha2-receptor agonist dexmedetomidine as the anesthetic drug. The aim
      of this study was to compare both mentioned techniques and evaluate the clinical
      use of dexmedetomidine in the setting of awake craniotomies for glioma surgery.
      METHODS The authors retrospectively analyzed patients who underwent operations
      either under the asleep condition using propofol-remifentanil or under conscious
      sedation conditions using dexmedetomidine infusions. In the asleep group patients
      were intubated with a laryngeal mask and extubated for the assessment period.
      Adverse events, as well as applied drugs with doses and frequency of usage, were
      recorded. RESULTS From 224 awake surgeries between 2009 and 2015, 180 were
      performed for the resection of gliomas and included in the study. In the
      conscious sedation group (n = 75) significantly fewer opiates (p < 0.001) and
      vasoactive (p < 0.001) and antihypertensive (p < 0.001) drugs were used in
      comparison with the asleep group (n = 105). Furthermore, the postoperative length
      of stay (p < 0.001) and the surgical duration (p < 0.001) were significantly
      lower in the conscious sedation group. CONCLUSIONS Use of dexmedetomidine creates
      excellent conditions for awake surgeries. It sedates moderately and acts as an
      anxiolytic. Thus, after ceasing infusion it enables quick and reliable clinical
      neurological assessment of patients. This might lead to reducing the amount of
      administered antihypertensive and vasoactive drugs as well as the length of
      hospitalization, while likely ensuring more rapid surgery.

PMID- 29328001
TI  - Gamma Knife radiosurgery of saccular aneurysms in a rabbit model.
AB  - OBJECTIVE Intracranial aneurysms are vascular abnormalities associated with
      neurological morbidity and mortality due to risk of rupture. In addition, many
      aneurysm treatments have associated risk profiles that can preclude the
      prophylactic treatment of asymptomatic lesions. Gamma Knife radiosurgery (GKRS)
      is a standard treatment for trigeminal neuralgia, tumors, and arteriovenous
      malformations. Aneurysms associated with arteriovenous malformations have been
      noted to resolve after treatment of the malformation. The aim of this study was
      to determine the efficacy of GKRS treatment in a saccular aneurysm animal model.
      METHODS Aneurysms were surgically produced using an elastase-induced aneurysm
      model in the right common carotid artery of 10 New Zealand white rabbits.
      Following initial observation for 4 years, each rabbit aneurysm was treated with
      a conformal GKRS isodose of 25 Gy to the 50% margin. Longitudinal MRI studies
      obtained over 2 years and terminal measures obtained at multiple time points were
      used to track aneurysm size and shape index modifications. RESULTS Aneurysms did
      not rupture or involute during the observation period. Whole aneurysm and blood
      volume averages decreased with a linear trend, at rates of 1.7% and 1.6% per
      month, respectively, over 24 months. Aneurysm wall percent volume increased
      linearly at a rate of 0.3% per month, indicating a relative thickening of the
      aneurysm wall during occlusion. Nonsphericity of the average volume, aspect
      ratio, and isoperimetric ratio of whole aneurysm volume all remained constant.
      Histopathological samples demonstrated progressive reduction in aneurysm size and
      wall thickening, with subintimal fibrosis. Consistent shape indices demonstrate
      stable aneurysm patency and maintenance of minimal rupture risk following
      treatment. CONCLUSIONS The data indicate that GKRS targeted to saccular aneurysms
      is associated with histopathological changes and linear reduction of aneurysm
      size over time. The results suggest that GKRS may be a viable, minimally invasive
      treatment option for intracranial aneurysm obliteration.

PMID- 29328002
TI  - Dexamethasone-mediated oncogenicity in vitro and in an animal model of
      glioblastoma.
AB  - OBJECTIVE Dexamethasone, a known regulator of mesenchymal programming in
      glioblastoma (GBM), is routinely used to manage edema in GBM patients.
      Dexamethasone also activates the expression of genes, such as CEBPB, in GBM stem
      cells (GSCs). However, the drug's impact on invasion, proliferation, and
      angiogenesis in GBM remains unclear. To determine whether dexamethasone induces
      invasion, proliferation, and angiogenesis in GBM, the authors investigated the
      drug's impact in vitro, in vivo, and in clinical information derived from The
      Cancer Genome Atlas (TCGA) cohort. METHODS Expression profiles of patients from
      the TCGA cohort with mesenchymal GBM (n = 155) were compared with patients with
      proneural GBM by comparative marker selection. To obtain robust data, GSCs with
      IDH1 wild-type (GSC3) and with IDH1 mutant (GSC6) status were exposed to
      dexamethasone in vitro and in vivo and analyzed for invasion (Boyden chamber,
      human-specific nucleolin), proliferation (Ki-67), and angiogenesis (CD31). Ex
      vivo tumor cells from dexamethasone-treated and control mice were isolated by
      fluorescence activated cell sorting and profiled using Affymetrix chips for mRNA
      (HTA 2.0) and microRNAs (miRNA 4.0). A pathway analysis was performed to identify
      a dexamethasone-regulated gene signature, and its relationship with overall
      survival (OS) was assessed using Kaplan-Meier analysis in the entire GBM TCGA
      cohort (n = 520). RESULTS The mesenchymal subgroup, when compared with the
      proneural subgroup, had significant upregulation of a dexamethasone-regulated
      gene network, as well as canonical pathways of proliferation, invasion, and
      angiogenesis. Dexamethasone-treated GSC3 demonstrated a significant increase in
      invasion, both in vitro and in vivo, whereas GSC6 demonstrated a modest increase.
      Furthermore, dexamethasone treatment of both GSC3 and GSC6 lines resulted in
      significantly elevated cell proliferation and angiogenesis in vivo. Patients with
      mesenchymal GBM had significant upregulation of dexamethasone-regulated pathways
      when compared with patients with proneural GBM. A prognostic (p = 0.0007) 33-gene
      signature was derived from the ex vivo expression profile analyses and used to
      dichotomize the entire TCGA cohort by high (median OS 12.65 months) or low
      (median OS 14.91 months) dexamethasone signature. CONCLUSIONS The authors present
      evidence that furthers the understanding of the complex effects of dexamethasone
      on biological characteristics of GBM. The results suggest that the drug increases
      invasion, proliferation, and angiogenesis in human GSC-derived orthotopic tumors,
      potentially worsening GBM patients' prognoses. The authors believe that careful
      investigation is needed to determine how to minimize these deleterious
      dexamethasone-associated side effects in GBM.

PMID- 29328003
TI  - Characterizing the type and location of intracranial abnormalities in mild
      traumatic brain injury.
AB  - OBJECTIVE The incidence of intracranial abnormalities after mild traumatic brain
      injury (TBI) varies widely across studies. This study describes the
      characteristics of intracranial abnormalities (acute/preexisting) in a large
      representative sample of head-injured patients who underwent CT imaging in an
      emergency department. METHODS CT scans were systematically analyzed/coded in the
      TBI Common Data Elements framework. Logistic regression modeling was used to
      quantify risk factors for traumatic intracranial abnormalities in patients with
      mild TBIs. This cohort included all patients who were treated at the emergency
      department of the Tampere University Hospital (between 2010 and 2012) and who had
      undergone head CT imaging after suffering a suspected TBI (n = 3023), including
      2766 with mild TBI and a reference group with moderate to severe TBI. RESULTS The
      most common traumatic lesions seen on CT scans obtained in patients with mild
      TBIs and those with moderate to severe TBIs were subdural hematomas, subarachnoid
      hemorrhages, and contusions. Every sixth patient (16.1%) with mild TBI had an
      intracranial lesion compared with 5 of 6 patients (85.6%) in the group with
      moderate to severe TBI. The distribution of different types of acute traumatic
      lesions was similar among mild and moderate/severe TBI groups. Preexisting brain
      lesions were a more common CT finding among patients with mild TBIs than those
      with moderate to severe TBIs. Having a past traumatic lesion was associated with
      increased risk for an acute traumatic lesion but neurodegenerative and ischemic
      lesions were not. A lower Glasgow Coma Scale score, male sex, older age, falls,
      and chronic alcohol abuse were associated with higher risk of acute intracranial
      lesion in patients with mild TBI. CONCLUSIONS These findings underscore the
      heterogeneity of neuropathology associated with the mild TBI classification.
      Preexisting brain lesions are common in patients with mild TBI, and the incidence
      of preexisting lesions increases with age. Acute traumatic lesions are fairly
      common in patients with mild TBI; every sixth patient had a positive CT scan.
      Older adults (especially men) who fall represent a susceptible group for acute CT
      positive TBI.

PMID- 29328004
TI  - Thoracolumbar Injury Classification and Severity Score in children: a reliability
      study.
AB  - OBJECTIVE There are many classification systems for injuries of the thoracolumbar
      spine. The recent Thoracolumbar Injury Classification and Severity Score (TLICS)
      has been shown to be a reliable tool for adult patients. The aim of this study
      was to assess the reliability of the TLICS system in pediatric patients. The
      validity of the TLICS system is assessed in a companion paper. METHODS The
      medical records of pediatric patients with acute, traumatic thoracolumbar
      fractures at a single Level 1 trauma center were retrospectively reviewed. A
      TLICS was calculated for each patient using CT and MRI, along with the
      neurological examination recorded in the patient's medical record. TLICSs were
      compared with the type of treatment received. Five raters scored all patients
      separately to assess interrater reliability. RESULTS TLICS calculations were
      completed for 81 patients. The mean patient age was 10.9 years. Girls represented
      51.8% of the study population, and 80% of the study patients were white. The most
      common mechanisms of injury were motor vehicle accidents (60.5%), falls (17.3%),
      and all-terrain vehicle accidents (8.6%). The mean TLICS was 3.7 +/- 2.8. Surgery
      was the treatment of choice for 33.3% of patients. The agreement between the
      TLICS-suggested treatment and the actual treatment received was statistically
      significant (p < 0.0001). The interrater reliability of the TLICS system ranged
      from moderate to very good, with a Fleiss' generalized kappa (kappa) value of
      0.69 for the TLICS treatment suggestion among all patients; however, interrater
      reliability decreased when MRI was used to contribute to the TLICS. The kappa
      value decreased from 0.73 to 0.57 for patients with CT only vs patients with
      CT/MRI or MRI only, respectively (p < 0.0001). Furthermore, the agreement between
      suggested treatment and actual treatment was worse when MRI was used as part of
      injury assessment. CONCLUSIONS The TLICS system demonstrates good interrater
      reliability among physicians assessing thoracolumbar fracture treatment in
      pediatric patients. Physicians should be cautious when using MRI to aid in the
      surgical decision-making process.

PMID- 29328005
TI  - A novel use of the NeuroBlate SideFire probe for minimally invasive disconnection
      of a hypothalamic hamartoma in a child with gelastic seizures.
AB  - The authors describe the case of a 22-month-old boy who presented with gelastic
      seizures and developmental delay. Magnetic resonance imaging and video
      electroencephalography monitoring revealed a primarily intraventricular
      hypothalamic hamartoma and gelastic seizures occurring 20-30 times daily. The
      patient was treated with various regimens of antiepileptic medications for 16
      months, but the seizures remained medically intractable. At 3 years of age, he
      underwent stereotactic laser ablation with an aim of disconnection of the lesion.
      The procedure was performed with the NeuroBlate SideFire probe. To the authors'
      knowledge, this is the first reported use of this technology for this procedure
      and serves as proof of concept. There were no perioperative complications, and 2
      years postprocedure, the patient remains seizure free with marked behavioral and
      cognitive improvements.

PMID- 29328006
TI  - Parent/guardian knowledge regarding implanted shunt type, setting, and symptoms
      of malfunction/infection.
AB  - OBJECTIVE Patients with shunts often interact with providers distant from their
      primary hospital, making it important that the parent(s)/guardian(s) is well
      versed in the type of shunt implanted and symptoms of malfunction/infection. This
      is particularly important with magnetic-sensitive programmable valves, as the use
      of MRI becomes more prevalent. METHODS Over a 6-month period, primary caregivers
      of 148 consecutive patients who received shunts were prospectively administered
      questionnaires at clinic visits. Caregivers were asked to do the following: 1)
      identify shunt valve name, type, and setting if applicable; 2) list symptoms of
      shunt malfunction/infection; and 3) indicate whether they had access to
      references regarding shunt type/setting, booklets from the Hydrocephalus
      Association, and quick reference cards with symptoms of shunt
      malfunction/infection. One cohort of caregivers (n = 75) was asked to carry
      informational cards with shunt valve/setting information (group I); this cohort
      was compared with another subgroup of caregivers (n = 73) not carrying cards
      (group II). RESULTS The mean (+/- SD) age of patients at implantation/revision
      was 3.71 +/- 4.91 years, and the age at follow-up was 6.12 +/- 5.4 years. The
      average time from surgery to administration of the questionnaire was 2.38 +/-
      3.22 years. There were 86 new shunt insertions and 62 revisions. One hundred
      twenty-eight caregivers (87%) could identify the type of valve (programmable vs
      nonprogrammable). On the other hand, only 72 caregivers (49%) could identify the
      valve name. Fifty-four of 73 (74%) caregivers of patients who had shunts with
      programmable valves could correctly identify the valve setting. One hundred
      caregivers (68%) had a copy of the Hydrocephalus Association booklet, and 103
      (70%) had quick reference cards. Eighty caregivers (54%) had references on shunt
      type/setting. Most caregivers (127 [86%]) could name >= 3 signs/symptoms of shunt
      malfunction, with vomiting (61%), headache (49%), and sleeps more/lethargic (35%)
      most frequently reported. Caregivers of patients in group I were more likely to
      have cards with symptoms of shunt infection or malfunction (p = 0.015); have
      information cards regarding shunt type/setting (p < 0.001); and correctly
      identify valve type (p = 0.001), name (p < 0.001), and setting if programmable (p
      = 0.0016). There were no differences in ability to list symptoms of shunt
      malfunction or infection (p = 0.8812) or in access to Hydrocephalus Association
      booklets (p = 0.1288). There were no significant demographic differences between
      the groups, except that group I patients had a shorter time from surgery to last
      follow-up (1.66 vs 3.17 years; p = 0.0001). CONCLUSIONS Education regarding the
      care of patients with shunts by providing written cards with shunt type/setting
      and access to reference materials seems to be effective. Developing plans for
      guided instruction with assessment in the clinic setting of a caregiver's
      knowledge is important for patient safety.

PMID- 29328007
TI  - [Prophylactic hydration to protect renal function from intravascular iodinated
      contrast material in patients at high risk of contrast-induced nephropathy
      (AMACING): a prospective, randomised, phase 3, controlled, open-label, non
      inferiority trial].
AB  - BACKGROUND: Intravenous saline is recommended in clinical practice guidelines as
      the cornerstone for preventing contrast-induced nephropathy in patients with
      compromised renal function. However, clinical-effectiveness and cost
      effectiveness of this prophylactic hydration treatment in protecting renal
      function has not been adequately studied in the population targeted by the
      guidelines, against a group receiving no prophylaxis. This was the aim of the
      AMACING trial. METHODS: AMACING is a prospective, randomised, phase 3, parallel
      group, open-label, non-inferiority trial of patients at risk of contrast-induced
      nephropathy according to current guidelines. High-risk patients (with an
      estimated glomerular filtration rate [eGFR] of 30-59 mL per min/1.73 m2) aged 18
      years and older, undergoing an elective procedure requiring iodinated contrast
      material administration at Maastricht University Medical Centre, the Netherlands,
      were randomly assigned (1:1) to receive intravenous 0.9% NaCl or no prophylaxis.
      We excluded patients with eGFR lower than 30 mL per min/1.73 m2, previous
      dialysis, or no referral for intravenous hydration. Randomisation was stratified
      by predefined risk factors. The primary outcome was incidence of contrast-induced
      nephropathy, defined as an increase in serum creatinine from baseline of more
      than 25% or 44 MUmol/L within 2-6 days of contrast exposure, and cost
      effectiveness of no prophylaxis compared with intravenous hydration in the
      prevention of contrast-induced nephropathy. We measured serum creatinine
      immediately before, 2-6 days, and 26-35 days after contrast-material exposure.
      Laboratory personnel were masked to treatment allocation. Adverse events and use
      of resources were systematically recorded. The non-inferiority margin was set at
      2.1%. Both intention-to-treat and per-protocol analyses were done. This trial is
      registered with ClinicalTrials.gov, number NCT02106234. FINDINGS: Between June
      17, 2014, and July 17, 2016, 660 consecutive patients were randomly assigned to
      receive no prophylaxis (n=332) or intravenous hydration (n=328). 2-6 day serum
      creatinine was available for 307 (92%) of 332 patients in the no prophylaxis
      group and 296 (90%) of 328 patients in the intravenous hydration group. Contrast
      induced nephropathy was recorded in eight (2.6%) of 307 non-hydrated patients and
      in eight (2.7%) of 296 hydrated patients. The absolute difference (no hydration
      vs hydration) was -0.10% (one-sided 95% CI -2.25 to 2.06; one-tailed p=0.4710).
      No hydration was cost-saving relative to hydration. No haemodialysis or related
      deaths occurred within 35 days. 18 (5.5%) of 328 patients had complications
      associated with intravenous hydration. INTERPRETATION: We found no prophylaxis to
      be non-inferior and cost-saving in preventing contrast-induced nephropathy
      compared with intravenous hydration according to current clinical practice
      guidelines.

PMID- 29328008
TI  - [Posttraumatic stress disorder: current insights in diagnostics, treatment and
      prevention].
AB  - - Posttraumatic stress disorder (PTSD) is a psychiatric disorder that may develop
      after traumatic events.- PTSD is one of the most prevalent psychiatric disorders
      in the Netherlands, with an estimated lifetime prevalence of 7%.- Recurrent re
      experiencing of the traumatic event is the most characteristic PTSD symptom.-
      Recognition of PTSD may be hampered by the heterogeneous symptomatology,
      avoidance to talk about the trauma and highly frequent comorbid psychiatric and
      somatic comorbidity.- Feelings of guilt and shame may also influence reported
      trauma history.- First choice treatment for PTSD is trauma-focused psychotherapy,
      which may be combined with pharmacotherapy.- In case of severe acute
      posttraumatic stress symptoms after a recent trauma, it is recommended to start
      early trauma-focused psychotherapy.- Neurobiological findings are increasingly
      applied in novel interventions to improve the treatment and prevention of PTSD.

PMID- 29328009
TI  - [A verrucous plaque on the lower leg].
AB  - A 10-year-old boy presented with an asymptomatic, congenital, dark brown
      coloured, well circumscribed, verrucous, hyperkeratotic plaque on his left leg.
      This was diagnosed as verrucous haemangioma.

PMID- 29328010
TI  - [Guideline 'The chronically ill and work'].
AB  - - The guideline 'The chronically ill and work' gives insight into disease
      overarching factors and interventions that can promote or impede the
      participation in the work process of workers and those looking for work who have
      a chronic condition. - In particular, the guideline focuses on the role taken on
      by workers or those looking for work themselves during the process of keeping or
      resuming work. - The guideline gives recommendations for the daily practice of
      healthcare providers which are based on knowledge from disease-specific
      guidelines, the international literature and the experiences of healthcare
      providers, and workers and those looking for work with a chronic condition.

PMID- 29328011
TI  - [Is there quality of life with locked-in syndrome?]
AB  - A 57-year-old man developed a locked-in state due to a brain stem stroke. He
      communicated through eye movements. The team suggested treatment should be
      discontinued, as there was no perspective of improvement. The family was very
      upset because they experienced sufficient quality of life. We investigated what
      'quality of life' means. The literature shows that severely ill and completely
      care-dependent patients may experience high quality of life; this is called the
      disability paradox. Patients and families evaluate quality of life by looking for
      positive things to live for. Some quality-of-life tests, however, understand
      quality of life as 'functionality'. Healthy people evaluate the situation of
      people living with handicaps more negatively than the handicapped themselves do.
      Practitioners may overlook the instability of patients' evaluations: responses
      and situations may shift. Quality of life as an outcome in clinical trials may be
      different for individual patients. These insights may improve communication.

PMID- 29328012
TI  - [A man with severe skin rash].
AB  - A 31-year-old man visited the outpatient clinic Dermatology with an exacerbation
      of his atopic eczema. Since a few day vesicles and crusts had appeared and his
      eyelids were swollen. He was known to have eczema, for which he was treated with
      ciclosporin 200 mg 2 times a day (4 mg/kg per day) since four months. Under this
      treatment the eczema used to be under control. There were no neurological
      symptoms or vision problems. At physical examination we saw erythematous papules,
      vesicles, superficial erosions and crusts on all body regions, but especially on
      the trunk and in the main neck region. The patient was diagnosed with eczema
      herpeticum and he was treated with intravenous aciclovir 1000 mg 3 times a day
      (10 mg/kg 3 dd) and flucloxacillin 1000 mg 4 times a day for seven days.

PMID- 29328013
TI  - [A woman with a painful and enlarged tongue].
AB  - A 53-year-old woman presented with painful macroglossia and periorbital papules.
      Based on this clinical features and biopsies the diagnosis of nodular amyloidosis
      was established. Further analysis revealed that multiple myeloma was the
      underlying hematological disorder.

PMID- 29328014
TI  - [Innovation in transport of critical care patients].
AB  - The differentiation of specialist care means that not every hospital can meet
      specific care requirements. Because of this, frequent transport of critical care
      patients is necessary. In most circumstances, regular ambulance transport is
      used, either with or without an accompanying physician. In some cases, a mobile
      intensive care unit (MICU) can be deployed. However, the MICU is not 24/7
      operational in our area and significant waiting times can occur. Additionally,
      space and resources in a regular ambulance are limited. We have therefore
      developed a new protocol, covering the transport of critical care patients. In
      this, we use a special trolley with built-in advanced devices, such as a
      respiratory apparatus, in combination with an adapted ambulance. By using this
      protocol we minimize time loss and guarantee safe and patient-centred transport.

PMID- 29328015
TI  - [A young man with extensive skin abnormalities].
AB  - A 26-year-old man who has sex with men visited the STI clinic because of
      increasing skin abnormalities since four months. The patient had macular skin
      lesions on his penis and scrotum, condylomata lata in the anal region, cutaneous
      lesions on the feet, and a widespread papular rash. A secondary stage of syphilis
      was diagnosed.

PMID- 29328016
TI  - [The yips: a movement disorder among golfers].
AB  - BACKGROUND: Although the yips occurs commonly in golfers, this neurological
      movement disorder is a relatively unknown phenomenon among physicians. CASE
      DESCRIPTION: A 47-year-old golf player developed a disturbing, neurological
      movement disorder that manifested when playing golf: the yips. These jerks
      occurred when putting, but not during practice rounds. The patient's father
      suffered from similar yips. CONCLUSION: The yips is a task-specific dystonia,
      which can also manifest in players of other sports. Multiple factors, such as
      genetic predisposition and anxiety seem to be involved in its pathophysiology.
      The disorder is relatively common among both professional and amateur golfers.
      The adverse impact can be big and a cure is yet to be found.

PMID- 29328017
TI  - [Hydration to prevent contrast-induced nephropathy].
AB  - In 2007, a national guideline was issued in the Netherlands to prevent contrast
      induced nephropathy. This guideline recommended preventive hydration with 0.9%
      NaCl in patients with reduced estimated glomerular filtration rate (eGFR 30-69
      ml/min/1.73 m2) prior to administration of contrast. The recent AMACING study
      compared hydration versus no hydration, and found that hydration did not prevent
      contrast-induced nephropathy but did lead to complications and higher costs. The
      latest 2017 guideline recommends hydration only for patients with eGFR < 30
      ml/min/1.73 m2. Although this is an improvement, an even more recent study,
      PRESERVE, showed no differences in the incidence of contrast-induced nephropathy
      between sodium chloride, sodium bicarbonate, acetylcysteine, or placebo - even in
      patients with lower eGFRs (15-60 ml/min/1.73 m2) undergoing elective angiography.
      This raises the question whether preventive measures are only effective in
      patients with the highest risk, i.e. hospitalized patients with multiple risk
      factors undergoing emergency procedures.

PMID- 29328018
TI  - [A day in the life of a medical resident on the ward].
AB  - OBJECTIVE: To investigate how internal medicine residents allocate their time
      during a hospital dayshift on the wards. DESIGN: Prospective observational cohort
      study (time and motion study). METHODS: Data were collected from 36 internal
      medicine residents working at the Internal Medicine Department of the Academic
      Medical Centre in Amsterdam, the Netherlands. Trained observers monitored 22
      residents using a newly developed smartphone-application, registering their
      dayshift activities (meetings and education, direct patient contact,
      administrative tasks, lunch/break, other) and location (workstation, conference
      room, ward and patient rooms, other). Data of 14 residents on work-related
      activities during after-hours in the hospital and at home were collected through
      a questionnaire. RESULTS: Residents were observed for a total of 210 hours. The
      average workday encompassed 9.5 hours. During this dayshift, residents spent an
      average of 38% of their time on administrative tasks, and 37% on
      interprofessional consultation and educational activities. Direct patient/family
      contact accounted for 13% of the workday. After the evening handover at 5 pm, on
      average another 80 minutes of work was performed in the hospital, of which 73
      minutes (91%) entailed administration. At home, they spent on average another 52
      minutes on patient care related work, of which 51 minutes (98%) consisted of
      administration. CONCLUSION: The internal medicine residents on the ward spend
      most of their dayshift on indirect patient care. This comprises mostly computer
      based administrative tasks. After the dayshift, many residents continue to work
      in their own time to finish remaining paperwork. Study limitations are the
      limited total number of monitored residents, the total observation time and
      possible self-report bias.

PMID- 29328019
TI  - Amygdala reactivity in ethnic minorities and its relationship to the social
      environment: an fMRI study.
AB  - BACKGROUND: Ethnic minority individuals have an increased risk of developing a
      psychotic disorder, particularly if they live in areas of ethnic segregation, or
      low own group ethnic density. The neurobiological mechanisms underlying this
      ethnic minority associated risk are unknown. We used functional MRI to
      investigate neural responses to faces of different ethnicity, in individuals of
      black ethnicity, and a control group of white British ethnicity individuals.
      METHODS: In total 20 individuals of black ethnicity, and 22 individuals of white
      British ethnicity underwent a 3T MRI scan while viewing faces of black and white
      ethnicity. Own group ethnic density was calculated from the 2011 census.
      Neighbourhood segregation was quantified using the Index of Dissimilarity method.
      RESULTS: At the within-group level, both groups showed greater right amygdala
      activation to outgroup faces. Between groups, the black ethnicity group showed
      greater right amygdala activation to white faces, compared to the white ethnicity
      group. Within the black ethnicity group, individuals living in areas of lower own
      group ethnic density showed greater right amygdala reactivity to white faces (r =
      -0.61, p = 0.01). CONCLUSIONS: This is the first time an increased amygdala
      response to white faces has been demonstrated in individuals of black ethnicity.
      In the black ethnicity group, correlations were observed between amygdala
      response and neighbourhood variables associated with increased psychosis risk.
      These results may have relevance for our understanding of the increased rates of
      paranoia and psychotic disorders in ethnic minority individuals.

PMID- 29328022
TI  - [ENDOMETRIOSIS: A NEW APPROACH TO ETIOLOGY AND PATHOGENESIS (REVIEW)].
AB  - Endometriosis is a dyshormonal immune-dependent genetically determined disease,
      which appears as an endometrioid tissue that grows outside the uterine.
      Endometriosis is one of the most urgent problems of medicine. To date, new
      concepts of the endometriosis etiology and pathogenesis have been developed, but,
      despite their abundance, there is no unified theory. Genetic and epigenetic
      factors result in changes in an expression of aromatase, steroidogenic factor 1,
      and estrogen receptors are suggested to be the main cause of endometriosis. These
      changes lead to an active synthesis of various pro-inflammatory agents and a
      nerve growth factor, that are important in the development of pain syndrome.
      Also, changes in the progesterone receptor functioning and the local progesterone
      resistance development decrease the antiproliferative activity, apoptosis, and
      the anti-inflammatory substances level, as well as increase the prostaglandin,
      metalloproteinase activity, and level of hypoxia factors. In addition, there are
      shreds of evidence that endometriosis is associated with the risk of malignant
      tumors development, so new concepts for understanding these mechanisms are
      actively developing. Some of these mechanisms are discussed in this review.

PMID- 29328023
TI  - FEATURES OF FORMATION OF COLLATERAL CIRCULATION IN PATIENTS WITH SUBCLAVIAN STEAL
      SYNDROME.
AB  - To date in patients with subclavian steal syndrome diagnosis is only grade of
      stenosis or localization of occlusion described. Authors recommend to take into
      account also type of a collateral compensation of cerebral circulation for
      selection of an optimal treatment The objective of the research was to study the
      features of formation of collateral circulation in patients with subclavian steal
      syndrome. The authors described changes in the direction of blood flow in the
      extracranial vessels of 42 patients with subclavian steal syndrome. Latent
      subclavian steal syndrome was detected in 26.2% of patients, transient subclavian
      steal syndrome was found in 54.8% of patients, and a persistent course of the
      disease was observed in 19.9% of patients. Symptoms of vertebrobasilar
      insufficiency were detected in 26.6% of patients, and combination of chronic
      upper extremity ischemia and vertebrobasilar insufficiency was diagnosed in 73.8%
      of patients. When analyzing the features of collateral circulation in 64.3% of
      patients the extracranial compensatory mechanism was observed being provided by
      three main groups of collateral hemodynamic reallocation: the occipito-vertebral
      hemodynamic mechanism of compensation was detected in 38.1% of cases, the thyroid
      compensatory mechanism was found in 16.7% of cases, and the brain stem-occipital
      compensatory mechanism was observed in 9.5% of cases. In 35.7% of patients the
      intracranial compensatory mechanism was observed being provided by two main
      groups of collateral hemodynamic reallocation: the vertebro-vertebral
      compensatory mechanism was found in 21.4% of cases and cerebrobasilar
      compensatory mechanism was detected in 14.3% of cases. Consideration of the
      features of collateral circulation in patients with subclavian steal syndrome may
      serve as a prognostic criterion for selecting an optimal treatment tactics.Each
      of compensatory mechanisms has its own hemodynamic peculiarities. The occipito-
      vertebral compensatory mechanism has the most positive influence on the
      compensationof hemodynamic failure of the vertebrobasilar basin.

PMID- 29328021
TI  - The presynaptic ribbon maintains vesicle populations at the hair cell afferent
      fiber synapse.
AB  - The ribbon is the structural hallmark of cochlear inner hair cell (IHC) afferent
      synapses, yet its role in information transfer to spiral ganglion neurons (SGNs)
      remains unclear. We investigated the ribbon's contribution to IHC synapse
      formation and function using KO mice lacking RIBEYE. Despite loss of the entire
      ribbon structure, synapses retained their spatiotemporal development and KO mice
      had a mild hearing deficit. IHCs of KO had fewer synaptic vesicles and reduced
      exocytosis in response to brief depolarization; a high stimulus level rescued
      exocytosis in KO. SGNs exhibited a lack of sustained excitatory postsynaptic
      currents (EPSCs). We observed larger postsynaptic glutamate receptor plaques,
      potentially compensating for the reduced EPSC rate in KO. Surprisingly, large
      amplitude EPSCs were maintained in KO, while a small population of low-amplitude
      slower EPSCs was increased in number. The ribbon facilitates signal transduction
      at physiological stimulus levels by retaining a larger residency pool of synaptic
      vesicles.

PMID- 29328024
TI  - ENDOMETRIAL POLYPS IN WOMEN OF REPRODUCTIVE AGE: CLINICAL AND PATHOGENE-TIC
      VARIATIONS.
AB  - The aim of the study was to study the relationship between the morphofunctional
      characteristics of the endometrium, hormonal homeostasis and microbiocenosis of
      the reproductive system in patients with endometrial polyps. The study involved
      130 patients aged 18-35 years: 34 patients with endometrial polyps, 30 patients
      with micropolyps, 36 patients with endometrial polyps and micropolyps, 30 healthy
      women of the control group. Hysteroscopy was performed for women who had been
      suspected for endometrial polyps and who had infertility or repeated recurrent
      miscarriages. Endometrial samples from healthy women were obtained by aspiration
      biopsy. The endometrial sections were immunostained with monoclonal antibodies
      against the specific markers of plasmacytes (CD138), NK cells (CD56, CD16), pan
      leukocytes (CD45), macrophages (CD68), cellular marker for proliferation (Ki-67),
      ER, PR. Bacteriological examination of the endometrium was performed by PCR and
      by cultivating aerobic and anaerobic microorganisms on special growth media. In
      all groups of women the content in blood serum for 3-5 day of a menstrual cycle
      of gonadotropic hormones (FSH, LH) and sex steroid hormones (estradiol,
      prolactin) was studied, for 21 days of a cycle estimated the content of
      progesterone. Level of an expression of receptors of progesterone and estrogen
      estimated in endometrium and at EP, also in I a cycle phase. Highlighted are
      separate clinical and pathogenetic variations of endometrial polyps: isolated
      polyps, micropolyps, polyps in conjunction with micropolyps. In the course of
      study, it was found that progesterone deficiency and local immune imbalance with
      severe hypofunctional NK cells against viral and fungal infestations result in
      excessive endometrial cell proliferation and development of an isolated polyp.
      The case of a polyp merging with micropolyps potentiates an active inflammatory
      process alongside all of the mechanisms mentioned above. Micropolyps as a
      macroscopic manifestation of an active inflammatory process in chronic
      endometritis are characterized by focal infiltrates of leukocytes (CD45),
      macrophages (CD68), plasmacells (CD138) and NK (CD56) cells, whose activity leads
      to excess abnormal proliferation of endometrium, even in the absence of hormone
      receptor disorders.

PMID- 29328020
TI  - The synaptic ribbon is critical for sound encoding at high rates and with
      temporal precision.
AB  - We studied the role of the synaptic ribbon for sound encoding at the synapses
      between inner hair cells (IHCs) and spiral ganglion neurons (SGNs) in mice
      lacking RIBEYE (RBEKO/KO). Electron and immunofluorescence microscopy revealed a
      lack of synaptic ribbons and an assembly of several small active zones (AZs) at
      each synaptic contact. Spontaneous and sound-evoked firing rates of SGNs and
      their compound action potential were reduced, indicating impaired transmission at
      ribbonless IHC-SGN synapses. The temporal precision of sound encoding was
      impaired and the recovery of SGN-firing from adaptation indicated slowed synaptic
      vesicle (SV) replenishment. Activation of Ca2+-channels was shifted to more
      depolarized potentials and exocytosis was reduced for weak depolarizations.
      Presynaptic Ca2+-signals showed a broader spread, compatible with the altered
      Ca2+-channel clustering observed by super-resolution immunofluorescence
      microscopy. We postulate that RIBEYE disruption is partially compensated by multi
      AZ organization. The remaining synaptic deficit indicates ribbon function in SV
      replenishment and Ca2+-channel regulation.

PMID- 29328025
TI  - THE PECULIARITIES OF THE STATE OF THE AUTONOMIC NERVOUS SYSTEM ESTIMATED BY THE
      METHOD OF HEART RATE VARIABILITY IN PATIENTS WITH CIRRHOSIS AND SYNTROPIC DAMAGES
      OF CARDIOVASCULAR SYSTEM.
AB  - In the article the features of the autonomic nervous system state were estimated
      by the method of heart rate variability in patients with cirrhosis with syntropic
      damages of cardiovascular system - cardiomyopathy and arterial hypotension. As a
      result of an examination of 50 patients with liver cirrhosis and cardiomyopathy
      (investigational group A), 54 patients with liver cirrhosis and arterial
      hypotension (investigational group B), and 45 patients with liver cirrhosis also
      those who don't have the damages of cardiovascular system (group of comparison)
      it was established that: 1) they have the peculiarities of vegetative imbalance
      the characteristics of which are the low summarized activity of vegetative
      influence on heart rhythm and special dynamics of indexes of percentage structure
      of general spectral power; 2) they depend on the clinical variant of this damage 
      in patients with cirrhosis and syntropic cardiomyopathy the regulating of
      internal processes involve the humoral-metabolic influence, i.e. local vasoactive
      conjunctions, catecholamines, renin-angiotensin-aldosterone system, with a
      simultaneous influence of sympathetic system and activity reduction of
      parasympathetic vegetative nervous system, and in patients with cirrhosis and
      syntropic arterial hypotension - the internal regulation involves the local
      humoral-metabolic factors with the lack of both sympathetic and parasympathetic
      parts of vegetative nervous system.

PMID- 29328026
TI  - CLINICAL EFFICACY OF S-ADENOSYLMETHIONINE IN PATIENTS WITH NON-ALCOHOLIC
      STEATOHEPATITIS AND CHRONIC KIDNEY DISEASE I-II STAGE.
AB  - The article presents a theoretical generalization of the results of the clinical
      efficacy of S-adenosylmethionine in patients with non-alcoholic steatohepatitis
      (NASH) in comorbidity with obesity and chronic kidney disease (CKD) of the 1st
      2nd stages. The objective of the article was to determine the likely effect of S
      adenosylmethionine and Meldonium on the clinical course of non-alcoholic
      steatohepatitis (NASH) and chronic kidney disease (CKD) of the I-II stages. We
      examined 75 patients with NASH with comorbid obesity I degree and CKD I and II
      dgrees. To determine the efficacy of the treatment, 3 groups of patients were
      randomized according to age, sex, degree of obesity, activity of the cytolytic
      syndrome of NASH and the stage of the CKD. SAM possesses powerful membrane
      stabilizing properties, stably eliminates the manifestations of cytolysis,
      cholestasis, mesenchymal-inflammatory syndrome, increases the albumin
      synthesizing function of the liver in patients with NASH and prevents the loss of
      albumins in the conditions of CKD I-II st. At the same time, complex therapy of
      SAM and vazonate is superior to the effectiveness of correction of these
      syndromes due to the implementation of powerful metabolic, antioxidant,
      antihypoxant, energy-specific properties of Meldonium and may be recommended for
      the introduction into the practice of internal medicine and gastroenterology for
      treatment NASH on the background of obesity and CKD I and II stages. The
      established nephroprotective properties of SAM that are potentiated by Meldonium
      are probably due to the ability of these drugs to eliminate endothelial
      dysfunction, improve microcirculation, and prevent the progression of kidney
      fibrosis. S-adenosylmethionine (ahepta) in a dose of 600 mg sublingually in
      patients with non-alcoholic steatohepatitis on the background of obesity and
      chronic kidney disease of the 1st and 2nd st. produces powerful membrane
      stabilizing effects on the affected hepatocytes, stably eliminates the clinical
      manifestations of the disease, the intensity of cytolysis, cholestasis,
      mesenchymal-inflammatory syndrome, inhibits the progression of hepatic and renal
      dysfunction (increases the albumin-synthesizing function of the liver, the
      velocity of glomerular filtration) by optimizing the control of fibrosis of the
      liver and kidneys. Complex therapy with S-adenosylmethionine (ahape) and
      Meldonium (500 mg /day)(vasonate) is superior to the correction of these
      syndromes NASH and CKD, since the vasonate potentially potentiates the action of
      S-adenosylmethionine in acute and distant observation periods.

PMID- 29328027
TI  - THE IMPACT OF 12-MONTH GROWTH HORMONE REPLACEMENT THERAPY ON LIPID METABOLISM AND
      ADIPOSE TISSUE DISTRIBUTION IN GEORGIAN PATIENTS WITH ADULT GROWTH HORMONE
      DEFICIENCY.
AB  - Growth hormone deficiency (GHD) is one of the reasons of significant metabolic
      morbidities inchildren and adults. The aim of our study was to evaluate the
      impact of growth hormone (GH) replacement therapy on lipid profile and adipose
      tissue distribution in adults with GHD. Twenty hypopituitary adults, aged 40.75+/
      2.2 years (mean +/- SE, range 20.5-60), with adult onset GHD (aGHD) were enrolled
      in a randomized, double blind, placebo-controlled study. 10 patients received
      recombinant growth hormone injection once weekly for 12 months, and the rest 10
      patients (as control group) received placebo. The patients were selected from the
      basis of National Institute of Endocrinology. After 12 months of treatment mean
      values of low density lipoprotein cholesterol (LDL-CH), total cholesterol (CH)
      and triglycerides (TG) were increased in GH treated patients, compared to the
      control group (median increase in LDL-CH, CH and TG were 0.1 mmol/l, 0.1 mmol/l
      and 0.3mmol/l, respectively). In contrast, the favorable effect was seen in high
      density lipoprotein cholesterol (HDL-CH) levels with the median increase of 0.2
      mmol/l). Furthermore, there was an increase in adipose tissue distribution
      percentages, in GH treated patients (DXA: Legs +10.22%, Trunk: +7.43%, Android:
      +5.59%, Gynoid: +10.59%, Total body: +7.6%), compared to the control group, in
      which adipose tissue distribution was slightly improved or remained unchanged.
      Since the results of 12-month growth hormone treatment therapy did not show any
      improvements in lipid profile and adipose tissue distribution, the decision was
      made to prolong the study for the next 12 months.

PMID- 29328028
TI  - [SKIN PATHOLOGY IN DIABETES MELLITUS: CLINICAL AND PATHOPHYSIOLOGICAL
      CORRELATIONS (REVIEW)].
AB  - Skin pathology is registered in vast majority of patients with diabetes mellitus
      (DM). Despite the abundance of publications on dermatological problems in DM,
      there is still a number of gaps to be discussed in terms of pathophysiological
      mechanisms. The goal of this review was to assess the mechanisms of development
      of different skin pathologies under DM. One of the key pathogenic mechanisms of
      skin lesions in diabetes is hyperglycemia and the effects of the advanced
      glycation end products, inducing oxidative stress, endothelial dysfunction and
      inflammation; that in its turn can accelerate the mechanisms of skin aging, the
      development of diabetic dermopathy and scleredema diabeticorum. Imbalance of
      growth factors, cytokines and hormones under insulin resistance, is associated
      with increased proliferation of keratinocytes, fibroblasts and sebocytes, mast
      cell dysfunction and melanogenesis disorders in acanthosis nigricans,
      acrochordons, acne and inflammatory dermatitis in diabetic patients. In addition,
      authors discuss the role of dendritic cells and macrophages dysfunction in
      impairment of peripheral tolerance and diabetic wounds pathogenesis in patients
      with DM.

PMID- 29328029
TI  - [METABOLIC SECRETION IN REPRODUCTIVE AGE WOMEN WITH OBESITY].
AB  - For the last decade melatonin has attracted attention as a neuroregulator in
      pathogenesis of obesity and metabolic syndrome. The aim of our study is to
      evaluate the characteristics of metabolic secretion in obese women of
      reproductive age. The study was conducted on the total number of 120 women.
      Eighty women with obesity formed the case group, and forty healthy women - the
      control group. Carbohydrate metabolism, lipid profile and serum levels of
      melatonin were evaluated in all study subjects. According to the results, 61.3%
      of the total study population had insulin resistance and 60% had dyslipidemia.
      Melatonin hypersecretion, with the mean level of melatonin 129.4+/-124.9, was
      observed in the case group. The mean level of melatonin in the control group was
      107.5+/-10.9, which was 17% less than in the case group. Melatonin secretion was
      in significant correlation with patients' age (P=0.022), family history of
      myocardial infarction (P=0.030), excess carbohydrate intake (P=0.051) and
      enlarged ovaries (P=0.050). Our results confirm the relationship between obesity,
      metabolic abnormalities (insulin resistance, dyslipidemia) and melatonin
      hypersecretion in women of reproductive age.

PMID- 29328030
TI  - MODERN APPROACHES TO FRACTIONAL EXHALED NITRIC OXIDE AS A USEFUL BIOMARKER FOR
      ALLERGIC ASTHMA PHENOTYPING AND MANAGEMENT.
AB  - Asthma is a pathologically heterogeneous disease, consisting of several
      phenotypes. Different types of airway inflammation are the cornerstone feature of
      this condition. Fraction of nitric oxide in exhaled air (FENO) has been proposed
      as a noninvasive, specific biomarker for eosinophilic airway inflammation and has
      been shown to be elevated in patients with allergic asthma phenotype. More recent
      studies indicate that FeNO identifies T-helper cell type 2 (Th2)-mediated airway
      inflammation with a high predictive value for identifying inhaled corticosteroid
      (ICS) responsive airway inflammation. Taking into account the accumulated
      evidence,it is possible to consider, that FeNO testing has an important role in
      the assessment of patients with suspected asthma and in the management of
      established asthmadiagnosis. In conjunction with symptom scores and lung function
      tests, FeNO measurement could provide a more useful and effective approach for
      asthma in terms of: (1) detecting the presence of Th2-mediated airway
      inflammation, (2) determining the likelihood of ICS responsive (and lack of
      course), (3) monitoring of airway inflammation to determine risk for future
      impairment or loss of asthma control during reduction/cessation of ICS treatment,
      (4) unmasking (otherwise unsuspected) non-adherence to corticosteroid therapy and
      (5) in severe asthma cases tailoring treatment with biological drugs. However,
      more work is still needed to address outstanding questions about its exact role
      in guiding asthma management and better define the use of FENO in different
      clinical settings.

PMID- 29328031
TI  - METABOLIC PROFILE OF SERUM FATTY ACIDS IN PATIENTS WITH COMORBIDITY OF CHRO-NIC
      OBSTRUCTIVE PULMONARY DISEASE AND CHRONIC PANCREATITIS.
AB  - Objective - study of blood serum fatty acid metabolic profile in patients with
      comorbidity of COPD and chronic pancreatitis. 238 patients were examined, of them
      131 with combined COPD and chronic pancreatitis and 107 with isolated COPD run.
      In study of fatty acid spectrum biological materials were prepared and gas
      chromatography analysis of blood serum lipid fatty acid spectrum performed
      according to methodology by L.V.Sazonenko et al. The study showed that COPD
      exacerbation was accompanied with by changes in contents of particular fatty
      acids both in patients with isolated COPD and in patients with comorbidity in
      comparison with almost healthy patients. In comparison of values for isolated
      COPD patients and comorbidity of COPD and chronic pancreatitis patients
      unidirectional deviations in concentrations of basic FAs were observed in both
      groups. Although concentrations of basic FAs mostly did not have probable
      discrepancies, nevertheless, concentration changes of stearic and linoleic acids
      were significantly more expressed, which caused saturation level reduction and
      increased unsaturation of fatty acids. The presence of concomitant chronic
      pancreatitis in patients with COPD substantially strengthened the expression of
      FAs spectrum deviations due to increase of unsaturation level and the sum of
      PSFAs which is indicative of lipid peroxidation processes intensification, and
      this may be treated as one of additional factors of pathology progressing.

PMID- 29328032
TI  - [TACTICS OF CHOOSING COGNITIVE DYSFUNCTION THERAPY IN THE POSTOPERATIVE PERIOD].
AB  - The aim of the study is to formulate the tactics of assigning adequate
      neuroprotective therapy to patients with postoperative cognitive dysfunctions on
      the basis of subtracting the indicator of the total cognitive deficiency. To
      achieve this goal, we conducted a study of cognitive function in patients of
      different age groups: young age, middle age, elderly age with acute surgical
      pathology before surgery and at 1, 7, 30 days after surgery compared with
      preoperative data. Methods of research. The study of the cognitive sphere: scale
      MMSE, test drawing hours, test "10 words", battery tests for frontal dysfunction,
      method Schulte. The indicator of the total cognitive deficiency was calculated. 
      The results of the study of cognitive function made it possible to formulate a
      scheme for the use of citicoline and cytoflavin in a complex of therapeutic
      programs. In each age group, on the seventh day of the study, there were patients
      with different dynamics of cognitive function recovery for the preoperative
      period. This allowed us to develop and propose a formula for calculating the
      total cognitive deficit, which makes it possible to formulate appropriate tactics
      for managing patients in the subsequent period in each specific case. We
      determine the values of the percentage deviations of each study result from the
      norm and the indicator of the total cognitive deficit by the sum of the values of
      the percentage deviation from the norm of the results of the study of cognitive
      impairment.

PMID- 29328033
TI  - [ELEMENTAL STATUS OF PATIENTS WITH VARIOUS FORMS OF VITILIGO].
AB  - Vitiligo is a multifactorial disease in which, in each specific case of its
      manifestation, different mechanisms of its pathogenesis and different levels of
      melanin formation in the skin can be involved. Skin is one of the most
      metabolically active organs. Carrying out a number of vital functions (barrier,
      protective, respiratory, excretory, metabolic, immune, etc.), it needs
      microelementss. Of the 92 naturally occurring chemical elements, 81 are found in
      the human body. Lack of the vital elements, leads to the emergence of diseases,
      which are based on deficiency, excess or imbalance of micro- and macroelements in
      the body. To assess the elemental status of patients with various forms of
      vitiligo, fluorescent x-ray spectroscopy was used. The method has good
      informativeness, since the hair most fully reflects the level of content of both
      toxic and vital elements. According to the results obtained, in patients with
      segmental vitiligo, a slight decrease in the content of manganese and copper was
      detected in the hair. In the group of patients with non-segmental form of
      vitiligo, along with a significant decrease in the concentration of basic
      elements (on average from 20 to 50%) copper, manganese, selenium, zinc, there was
      an increase in the indices of such toxic elements as lead and cadmium. The data
      of multi-element hair analysis, as are confirmed by well-known information about
      the role of certain chemical elements in the pathogenesis of vitiligo, also allow
      us to make new assumptions about the possible relationship between the violation
      of the microelement balance of the organism with the emergence and peculiarity of
      the flow of various forms of vitiligo. The correct approach to understanding the
      mechanisms of the emergence of vitiligo, will allow to offer new effective
      schemes for the treatment of vitiligo.

PMID- 29328034
TI  - CHARACTERISTICS OF ARTICULAR SYNDROME IN SYSTEMIC VASCULITIS.
AB  - The purpose of the study - investigation the separate joint lesion in systemic
      vasculitis, their X-ray sonographic characteristics, the correlation of the
      articular syndrome severity with extra-articular manifestations of the diseases,
      as well as aspects of the arthritis pathogenesis in this category of patients.
      The study included 525 patients in the ratio of the examined with Henoch-Schonlen
      purpura, microscopic polyangiitis, cryoglobulinemic vasculitis, polyarteritis
      nodosa, Takayasu's arteritis, Wegener's granulomatosis with polyangiitis and
      eosinophilic granulomatosis with polyangiitis Churg-Strauss as a 7:4:3:1:1:1:1.
      Joint's damage in the form of arthritis or arthralgia observed in 32-67%
      different groups of patients, that depending on the disease duration, the degree
      of the pathological process's activity, extraarticular signs severity, lung
      parenchyma involving and hemodynamic status in the pulmonary circulation. The
      frequency of the certain bone lesions, existence of tenosynovitis and
      enthesopathies, X-ray sonographic signs of articular syndrome in different kind
      of vasculitis has its own gender dimorphism. The immune system malfunction, the
      rheological properties of blood and endothelial function of vessels collaborate
      in pathogenetic constructions of arthropathy. What is more, the high value of
      rheumatoid factor in blood associates with severe course of joint damage. Joint
      syndrome at different variants of systemic vasculitis is progressing in 1/3-2/3
      of cases, this syndrome has definite features of clinical course and
      pathogenesis.

PMID- 29328035
TI  - ASSESSMENT OF NEURODEVELOPMENTAL OUTCOMES IN INFANTS 6-12 MONTHS OF AGE ACCORDING
      TO IMPACT OF PERINATAL RISK FACTORS.
AB  - The purpose of this research was to investigate the developmental follow-up of
      infants (at age of 6 month and 12 month), exposed to separate and combination
      impact of perinatal risk factors, compared with not exposed cases, within the
      prospective cohort study. Between January 2015 and January 2017, in this research
      we prospectively enrolled 1018 live-born infants from the medical reports of the
      participating clinics in Tbilisi (capital of Republic of Georgia) and Mtskheta,
      Dusheti (districts of Georgia). Within postnatal follow-up, the children from
      whole population were assessed at 6 and 12 months of age by family doctors using
      the Denver Developmental Screening Test (Denver II). The association between the
      risk factors and neurodevelopmental outcomes was analyzed by Chi-square test of
      independence. Statistical analysis of these data was performed using the SPSS
      version 12. (SPSS Inc., Chicago, IL). A P value of less than 0.05 was considered
      as significant. Prevalence of abnormal development in whole population was
      revealed 9.0% or 92 cases at age of 6 month and 36 cases or 3.5% at age of 12
      month. Point prevalence of farther neurodevelopmental adversities for healthy
      born children not influenced by studied risk factors was 0.1% and for infants
      with impact of the risk factors - 1.5%; on the other hand, prevalence of observed
      abnormal development in infant's population who had neonatal pathologies was 2.3%
      if risk factors were not exposed and 21.6% under influence of risk factors.
      Statistical analysis showed that an abnormal developmental outcomes were more
      frequent when researched risk factors were exposed (OR-23.18, CI 95% - 11.83 to
      45.41 - at age of 6 month; OR - 26.12, CI 95% - 7.95 to 85.85 - at age of 12
      month) as well, as correlation of these risk factors with neurodevelopmental
      adverse outcomes was significant (p<0.001). Significant correlations were
      identified for separate risk factors, such as maternal age (<17Y>35Y),
      pathologies of pregnancy and delivery as well as gestation age (<37 weeks).
      Coexistence of revealed risk factors increased probability of adverse
      neurological outcomes in infants at age of 6 month as well as at age of 12 month.
      There was a statistically important association between infant's 1-year
      neurological outcomes and these perinatal risk factors.

PMID- 29328036
TI  - [STRUCTURE AND RISK FACTORS FOR CONGENITAL MALFORMATIONS].
AB  - Congenital malformations and anomalies occupy leading positions in the structure
      of infant mortality and disability. In order to reduce the risk of children with
      these disorders, it is necessary to carefully study the causes of congenital
      malformations. In this connection, the structures and risk factors of congenital
      malformations of the fetus were studied and recommendations for the improvement
      of preventive measures were developed. When studying the structure of congenital
      malformations of the fetus in Almaty, hereditary and acquired causes of
      congenital malformation are identified. In the course of the study, the main risk
      factors for fetal development of the fetus were studied, where the main
      predictors were identified. The main age of women, 30-46 years old, whose
      pregnancy is susceptible to fetal malformation, has been determined. On the basis
      of the data obtained, recommendations are given on improving the sanitary
      literacy among women, creating a healthy lifestyle and ensuring prevention.

PMID- 29328037
TI  - [IMPLEMENTATION OF THE RIGHT FOR HEALTH CARE FOR CHILDREN - INTERNALLY DISPLACED
      PERSONS (CERTAIN ASPECTS)].
AB  - The aim of the article is to do a research on selected issues related to
      realizing the right for health sare for the children - internally dislocated
      persons. In order to achieve the given aim statistical data of the quantity of
      involuntarily dislocated persons including children and also the quantity of
      children registered with the health-care authority as well as the quantity of
      their requests for medical care have been analized. It has been determined that
      in case of involuntary dislocation children are more often exposed to trauma than
      adults which leads to different emotional disorders. The concepts of "the right
      for health care" in international legal acts, national legislation of Ukraine and
      scientific works have been analized. There have been defined three levels of the
      provision of the right for health care of internally dislocated persons. It has
      been substantiated that the fact that a child has not been registered with the
      health-care authority as IRP can't be a ground for limitations in realization of
      his right on health care. During the research process it has been defined that
      children IRP need medical care more often than other internally dislocated
      persons and in realization of the right for health care they come across a number
      of problems that need urgent solution, including access to free of charge
      professional medical care, regardless of the fact of medical registration of a
      child IRP, insufficient funding for provision of the needs of children IRP with
      medications, absence of obligatory primary medical examination of children IRP,
      etc.

PMID- 29328038
TI  - QUANTITATIVE ASSESSMENT OF THE RESULTS OF VIMENTIN IMMUNOHISTOCHEMICAL
      EXAMINATION IN FIBROBLASTS AND ENDOTHELIOCYTES OF THE PLACENTAL VILLI IN THE
      ASPECT OF PRETERM MATURATION OF THE CHORIONIC TREE AND IRON DEFICIENCY ANEMIA OF
      GRAVIDAS.
AB  - The objective of our study was to investigate quantitative parameters of vimentin
      in fibroblasts and endotheliocytes of the chorionic villi by means of
      immunohistochemical examination of placenta with preterm maturation of the
      chorionic tree with iron-deficiency anemia of pregnancy in two different terms of
      gestation - 29-32 weeks and 33-36 weeks. 182 placentas were examined. The study
      design included two main groups of investigation of the above terms of gestation
      and three groups of comparison. Quantitative parameters of vimentin in the
      cytoplasm of fibroblasts and endotheliocytes of the placenta intermediate and
      terminal villi were considered on the basis of staining optic density measured by
      means of computer microdensitometry method. Immunohistochemical staining on
      vimentin was determined in the cytoplasm of fibroblasts and endotheliocytes of
      the placenta intermediate and terminal villi in all the groups of the study. The
      main results are presented in the conclusions. Optic density of
      immunohistochemical staining on vimentin in the cytoplasm of fibroblasts and
      endotheliocytes of the placenta intermediate and terminal villi was found to be a
      criterion to determine maturation of the placenta chorionic tree. Iron-deficiency
      anemia paradoxically causes immaturity of fibroblasts and endotheliocytes of the
      placenta intermediate and terminal villi even in those placentas where preterm
      maturation of the chorionic tree is determined.

PMID- 29328039
TI  - INFLUENCE OF METABOLIC SYNDROME ON CONDITION OF MICROCIRCULATORY BED OF ORAL
      CAVITY.
AB  - Metabolic syndrome (MS) can be characterized as the clustering of combination of
      impaired glucose regulation, metabolic disorders accompanied by abdominal
      obesity, hyperglycemia, high blood pressure and dyslipidemia. Detection of
      changes in microcirculatory bed (MCB) of oral cavity in metabolic syndrome could
      be important for completion of gap for developing of adequate therapeutical
      measure for prevention of pathological periodontal disorder that was the purpose
      of our study. We performed experimental investigation with modulation of MS (on
      white male rats 1.5-2 months of age) during 70 days using a diet in which the
      oral pork fat was daily administered orally (40% of the rat weight), and 10%
      fructose ad libitum solution was used also instead of drinking water. Obtained
      specimens of soft tissues of the oral cavity were stained with histological and
      histochemical methods. The microscopic study with statistical analysis was
      performed. As result of our work it is established that metabolic syndrome is
      realized in significant changes in the microcirculatory bed of the periodontal,
      which can underlie the pathogenesis of inflammatory changes. Microcirculation
      disorders are characterized by significant changes in microangioarchitecture with
      uneven congestion, reduced specific volume of MCB vessels, thickening of vascular
      walls. Specific density of MCB vessels is changed from 27.40+/-8.31 % to 13.16+/
      1.94 % statistically. Growth of connective tissue is developed as result of
      hypoxia with presence of collagen fibers in all layers of oral mucosa lamina
      propria. Specific density of rough connective tissue is increased from 21.47+/
      6.38 % to 39.87+/-5.39 %.

PMID- 29328040
TI  - EXPRESSION OF CYCLIN E IN BASAL-LIKE BREAST CARCINOMA.
AB  - Results of study under 362 patients biopsy materials in Tbilisi National Cancer
      Center were shown that basal-like type breast carcinoma is characterizes by
      different reaction on Cyclin E, CK5/17 and ER/PR immunoreactivities. Basal-like
      tumor immunoreactivity on Cyclin E differs based they clinical stage and seen
      maximum correlation with III-IV stage and poor prognosis.

PMID- 29328041
TI  - VON WILLEBRAND FACTOR IMMUNOHISTOCHEMICAL STAINING QUANTITATIVE OPTICAL DENSITY
      PARAMETERS IN THE ENDOTHELIUM AND FIBRINOID OF THE PLACENTA DURING SECUNDINES
      INFLAMMATION AND CONCOMITANT IRON DEFICIENCY ANEMIA IN GRAVIDAS.
AB  - The aim of the research was to set the optical density quantitative parameters of
      the von Willebrand factor immunohistochemical staining (vWF) in the endothelium
      and fibrinoid of the placenta during the secundines inflammation concomitant with
      iron deficiency anemia in gravidas. The total number of 198 placentas was
      studied. The immunohistochemical technique was performed using the visualization
      of the primary antibodies to vWF with a diaminobenzidine dye polymer system. The
      optical density of the histochemical staining was measured by means of computer
      microdensitometry after the digital copies of the images had been obtained. All
      the cases of the secundines inflammation and the structures under study were
      found to have a significant increase in the optical density of the vWF
      immunohistochemical staining in the endothelium of the blood vessels as compared
      to the physiological pregnancy. Iron deficiency anemia in gravidas (IDAG)
      contributes to an increase in the indices of the inflammation, the highest data
      pertaining to the endothelial cells of the placental basal plate in chronic basal
      deciduitis. The optical density of the staining in the fibrinoid of the chorionic
      and basal plates during chronic forms of chorioamnionitis and basal deciduitis is
      higher than the optical density inherent in physiological pregnancy. The
      intensity of staining increases in presence of all the forms of inflammation on
      the background of IDAG in comparison with physiological pregnancy with placenta
      inflammation. Compared with IDAG in absence of the inflammatory processes, only
      chronic inflammatory processes reveal a change in indices. Consequently, the
      optical density of the staining significantly increases in the endothelium of
      blood vessels in all forms of the secundines inflammation, in comparison with the
      physiological pregnancy, whereas in fibrinoid the same process is reported only
      in chronic course. In this case, IDAG is accompanied by maximum levels of optical
      density in the endothelium and fibrinoid, whereas in chronic, the average indices
      are higher than those in acute forms.

PMID- 29328042
TI  - DYNAMICS OF CHANGES IN INDICES OF ENDOGENOUS INTOXICATION IN PATIENTS WITH ACUTE
      SMALL INTESTINAL OBSTRUCTION IN CASE OF REAMBERIN USE IN THE COMPREHENSIVE
      TREATMENT.
AB  - The objective of this research was to study changes in parameters, characterizing
      endogenous intoxication in patients with acute small bowel obstruction with
      Reamberin included into therapy scheme. Full physical examination and surgical
      treatment of 202 patients with acute small bowel obstruction were conducted. The
      control group included 30 healthy individuals. Dynamics of such clinical
      biochemical parameters as medium mass molecules (MMM), malondialdehyde (MDA),
      diene conjugates (DC) in blood serum were analyzed in preoperative period and on
      the 1st, 5th and 14th day of postoperative period. Significant free radical
      production occurred both in preoperative period and after surgical intervention.
      This was the reason to include antioxidant therapy using Reamberin (STPF
      "POLYSAN") in addition to basic treatment. The drug is approved for use by
      Central Formulary Committee of the Ministry of Health of Ukraine. All patients
      were divided into 2 groups depending on the treatment scheme. Group I consisted
      of 100 patients with acute small bowel obstruction who underwent the
      comprehensive treatment according to recommendations of the Ministry of Health of
      Ukraine No 297 dated 02.04.2010 (Standards of medical care for patients with
      urgent surgical diseases of the abdominal cavity). 102 patients of group II
      received the comprehensive treatment of antihypoxant and antioxidant therapy with
      Reamberin added to basic scheme. The main active ingredient of Reamberin is
      succinic acid. The drug was administered intravenously by drop infusion in a dose
      of 400 ml a day during 7-day period. Administration rate did not exceed 90 drops
      per minute. The medicine administration was started during complex preoperative
      preparation and then was done immediately after the completion of surgical
      treatment under resuscitation conditions. It was shown that the use of Reamberin
      promotes effective correction of free radical imbalance, reduction of endogenous
      intoxication and postoperative complications.

PMID- 29328043
TI  - COMPLEMENTARY AND ALTERNATIVE MEDICINE AND MEDICAL EDUCATION IN GEORGIA: STATE OF
      THE ART AND FURTHER PERSPECTIVES.
AB  - Aim - complementary and alternative medicine (CAM) is popular in Georgia, but
      providers' training not well understood or regulated. The aim of this mixed
      methods study was to inform the process of implementing quality CAM curricula in
      Georgia and strategies for the inclusion of effective CAM curricula into medical
      education in Georgia. We analyzed existing medical curricula. We conducted a
      contextual analysis based of qualitative data collected from relevant medical
      education experts, qualified physicians, CAM practitioners and other
      stakeholders; and administered a quantitative MD students' survey to MD students.
      CAM components are currently not represented in medical curricula in Georgia.
      Physicians largely lack adequate knowledge of CAM and its practice. All
      stakeholders supported that it would be beneficial to develop CAM educatory
      courses, both to future practitioners (medical students, initially as an elective
      subject) and practicing physicians (through CME). We recommend
      development/integration of an elective subject and/or a curricular component as a
      first step of CAM integration into the medical curricula in Georgia for MD
      students and CME courses for physicians. Interdisciplinary and international
      collaborations may help achieve best outcome, and safe practice of CAM in
      Georgia, forming a base for physician - CAM practitioner collaborations for
      quality care for patients in Georgia.

PMID- 29328044
TI  - A COMPUTER MODELING STUDY OF BINDING PROPERTIES OF CHIRAL NUCLEOPEPTIDE FOR
      BIOMEDICAL APPLICATIONS.
AB  - Nucleopeptides often show interesting properties of molecular binding that render
      them good candidates for development of innovative drugs for anticancer and
      antiviral therapies. In this work we present results of computer modeling of
      interactions between the molecules of hexathymine nucleopeptide (T6) and poly rA
      RNA (A18). The results of geometry optimization calculated using Hyperchem
      software and our own computer program for molecular docking show that molecules
      establish stable complexes due to the complementary-nucleobase interaction and
      the electrostatic interaction between the negative phosphate group of poly rA and
      the positively-charged residues present in the cationic nucleopeptide structure.
      Computer modeling makes it possible to find the optimal binding configuration of
      the molecules of a nucleopeptide and poly rA RNA and to estimate the binding
      energy between the molecules.

PMID- 29328045
TI  - ASSESSMENT OF THE LEVEL OF KNOWLEDGE OF MEDICAL PERSONNEL IN DIARRHEA AND
      HEMOLYTIC-UREMIC SYNDROME.
AB  - Survey have been conducted among medical professionals to test knowledge level of
      HUS and diarrheal diseases and to identify predictor variables for better
      knowledge. Cross-sectional survey have been conducted among medical personnel at
      different clinics in Tbilisi and in regions of Georgia. Participants were
      selected from different clinics in Tbilisi and in three biggest regional cities
      (Zugdidi, Batumi and Kutaisi) of Georgia. A total of 12 clinics were selected
      from them 6 were in Tbilisi and 2 at each regional cities. Clinics were selected
      based on their ability to provide services for gastrointestinal diseases,
      infectious diseases and kidney diseases. Data were entered into electronic
      database and analyzed using R v3.3.2. Descriptive statistics and methods of
      multivariate analysis were used for data analysis. 366 medical personnel have
      been interviewed. 73% (267) were females and 27% (99) males. Mean age was 40.8,
      IQR (27-52). A total of 64% (235) participants were from clinics located in
      Tbilisi. In multivariate analysis background in infectious diseases, female sex
      and having more than 10 years of medical experience were significantly associated
      with the total knowledge score of diarrheal diseases (p<0.05). High total
      knowledge score of HUS was detected among pediatricians (p<0.05). Trainings has
      been recommended for medical specialists to increase knowledge of diarrheal
      diseases and HUS to be able to identify those condition and to provide timely
      medical support for patients.

PMID- 29328046
TI  - Spatiotemporal radiotherapy planning using a global optimization approach.
AB  - This paper aims at quantifying the extent of potential therapeutic gain, measured
      using biologically effective dose (BED), that can be achieved by altering the
      radiation dose distribution over treatment sessions in fractionated radiotherapy.
      To that end, a spatiotemporally integrated planning approach is developed, where
      the spatial and temporal dose modulations are optimized simultaneously. The
      concept of equivalent uniform BED (EUBED) is used to quantify and compare the
      clinical quality of spatiotemporally heterogeneous dose distributions in target
      and critical structures. This gives rise to a large-scale non-convex treatment
      plan optimization problem, which is solved using global optimization techniques.
      The proposed spatiotemporal planning approach is tested on two stylized cancer
      cases resembling two different tumor sites and sensitivity analysis is performed
      for radio-biological and EUBED parameters. Numerical results validate that
      spatiotemporal plans are capable of delivering a larger BED to the target volume
      without increasing the BED in critical structures compared to conventional time
      invariant plans. In particular, this additional gain is attributed to the
      irradiation of different regions of the target volume at different treatment
      sessions. Additionally, the trade-off between the potential therapeutic gain and
      the number of distinct dose distributions is quantified, which suggests a
      diminishing marginal gain as the number of dose distributions increases.

PMID- 29328047
TI  - Optimal multichannel transmission for improved cr-MREPT.
AB  - Magnetic resonance electrical properties tomography (MR-EPT), aiming at
      reconstructing the EP's at radio frequencies, uses the H + field (both magnitude
      and phase) distribution within the object. One of the MR-EPT algorithms, cr
      MREPT, accurately reconstructs the internal tissue boundaries, however, it faces
      an artifact which occurs at the regions where the convective field, [Formula: see
      text], [Formula: see text], has a low magnitude (at the noise level). This study
      aims to develop an artifact-free conductivity reconstruction by modifying the H +
      field inside the region of interest (ROI), using multiple RF transmission
      techniques in MRI. An eight channel multi-transmit transverse electromagnetic
      array is used in two different drive configurations. The first drive is the
      standard volume excitation configuration where all ports are driven with the same
      magnitude and with 45 degrees  phase increment between adjacent channels. In the
      second drive, the drive voltage magnitude and phases for each of the eight drive
      ports are modified to generate a desired H + distribution such that the low
      convective field region moves to another non-overlapping position. Finally, data
      from both drive experiments are simultaneously used to reconstruct EP's. Computer
      simulations using cylindrical phantoms and a brain model are conducted and it is
      shown that the low convective field artifact can be eliminated. It is further
      shown that it is not necessary to re-calculate the port drive RF voltage
      magnitude and phases for each patient. The implementation issues of this method
      are briefly discussed.

PMID- 29328049
TI  - PET attenuation correction for rigid MR Tx/Rx coils from 176Lu background
      activity.
AB  - One challenge for PET-MR hybrid imaging is the correction for attenuation of the
      511 keV annihilation radiation by the required RF transmit and/or RF receive
      coils. Although there are strategies for building PET transparent Tx/Rx coils,
      such optimised coils still cause significant attenuation of the annihilation
      radiation leading to artefacts and biases in the reconstructed activity
      concentrations. We present a straightforward method to measure the attenuation of
      Tx/Rx coils in simultaneous MR-PET imaging based on the natural 176Lu background
      contained in the scintillator of the PET detector without the requirement of an
      external CT scanner or PET scanner with transmission source. The method was
      evaluated on a prototype 3T MR-BrainPET produced by Siemens Healthcare GmbH, both
      with phantom studies and with true emission images from patient/volunteer
      examinations. Furthermore, the count rate stability of the PET scanner and the x
      ray properties of the Tx/Rx head coil were investigated. Even without energy
      extrapolation from the two dominant gamma energies of 176Lu to 511 keV, the
      presented method for attenuation correction, based on the measurement of 176Lu
      background attenuation, shows slightly better performance than the coil
      attenuation correction currently used. The coil attenuation correction currently
      used is based on an external transmission scan with rotating 68Ge sources
      acquired on a Siemens ECAT HR  +  PET scanner. However, the main advantage of the
      presented approach is its straightforwardness and ready availability without the
      need for additional accessories.

PMID- 29328048
TI  - A biomechanical modeling-guided simultaneous motion estimation and image
      reconstruction technique (SMEIR-Bio) for 4D-CBCT reconstruction.
AB  - Reconstructing four-dimensional cone-beam computed tomography (4D-CBCT) images
      directly from respiratory phase-sorted traditional 3D-CBCT projections can
      capture target motion trajectory, reduce motion artifacts, and reduce imaging
      dose and time. However, the limited numbers of projections in each phase after
      phase-sorting decreases CBCT image quality under traditional reconstruction
      techniques. To address this problem, we developed a simultaneous motion
      estimation and image reconstruction (SMEIR) algorithm, an iterative method that
      can reconstruct higher quality 4D-CBCT images from limited projections using an
      inter-phase intensity-driven motion model. However, the accuracy of the intensity
      driven motion model is limited in regions with fine details whose quality is
      degraded due to insufficient projection number, which consequently degrades the
      reconstructed image quality in corresponding regions. In this study, we developed
      a new 4D-CBCT reconstruction algorithm by introducing biomechanical modeling into
      SMEIR (SMEIR-Bio) to boost the accuracy of the motion model in regions with small
      fine structures. The biomechanical modeling uses tetrahedral meshes to model
      organs of interest and solves internal organ motion using tissue elasticity
      parameters and mesh boundary conditions. This physics-driven approach enhances
      the accuracy of solved motion in the organ's fine structures regions. This study
      used 11 lung patient cases to evaluate the performance of SMEIR-Bio, making both
      qualitative and quantitative comparisons between SMEIR-Bio, SMEIR, and the
      algebraic reconstruction technique with total variation regularization (ART-TV).
      The reconstruction results suggest that SMEIR-Bio improves the motion model's
      accuracy in regions containing small fine details, which consequently enhances
      the accuracy and quality of the reconstructed 4D-CBCT images.

PMID- 29328050
TI  - Threshold-driven optimization for reference-based auto-planning.
AB  - We study threshold-driven optimization methodology for automatically generating a
      treatment plan that is motivated by a reference DVH for IMRT treatment planning.
      We present a framework for threshold-driven optimization for reference-based auto
      planning (TORA). Commonly used voxel-based quadratic penalties have two
      components for penalizing under- and over-dosing of voxels: a reference dose
      threshold and associated penalty weight. Conventional manual- and auto-planning
      using such a function involves iteratively updating the preference weights while
      keeping the thresholds constant, an unintuitive and often inconsistent method for
      planning toward some reference DVH. However, driving a dose distribution by
      threshold values instead of preference weights can achieve similar plans with
      less computational effort. The proposed methodology spatially assigns reference
      DVH information to threshold values, and iteratively improves the quality of that
      assignment. The methodology effectively handles both sub-optimal and infeasible
      DVHs. TORA was applied to a prostate case and a liver case as a proof-of-concept.
      Reference DVHs were generated using a conventional voxel-based objective, then
      altered to be either infeasible or easy-to-achieve. TORA was able to closely
      recreate reference DVHs in 5-15 iterations of solving a simple convex sub
      problem. TORA has the potential to be effective for auto-planning based on
      reference DVHs. As dose prediction and knowledge-based planning becomes more
      prevalent in the clinical setting, incorporating such data into the treatment
      planning model in a clear, efficient way will be crucial for automated planning.
      A threshold-focused objective tuning should be explored over conventional methods
      of updating preference weights for DVH-guided treatment planning.

PMID- 29328051
TI  - In situ synthesized SnO2 nanorod/reduced graphene oxide low-dimensional structure
      for enhanced lithium storage.
AB  - A unique SnO2 nanorod (NR)/reduced graphene oxide (RGO) composite morphology has
      been synthesized using the in situ hydrothermal method, for use as an anode
      material in lithium-ion batteries. The SnO2 NR adhering to the RGO exhibits a
      length of 250-400 nm and a diameter of 60-80 nm without any obvious aggregation.
      The initial discharge/charge capacities of the SnO2 NR/RGO composite are 1761.3
      mAh g-1 and 1233.1 mAh g-1, with a coulombic efficiency (CE) of 70% under a
      current density of 200 mA g-1, and a final capacity of 1101 mAh g-1 after 50
      cycles. The rate capability of the SnO2 NR/RGO is also improved compared to that
      of bare SnO2 NR. The superior electrochemical performance is ascribed to the
      special morphology of the SnO2 NRs-which plays a role in shorting the
      transmission path-and the sheet-like 2D graphene, which prevents the
      agglomeration of SnO2 and enhances conductivity during the electrochemical
      reaction of SnO2 NR/RGO.

PMID- 29328052
TI  - Shear-driven phase transformation in silicon nanowires.
AB  - We report on an unprecedented formation of allotrope heterostructured Si
      nanowires by plastic deformation based on applied radial compressive stresses
      inside a surrounding matrix. Si nanowires with a standard diamond structure (3C)
      undergo a phase transformation toward the hexagonal 2H-allotrope. The
      transformation is thermally activated above 500  degrees C and is clearly driven
      by a shear-stress relief occurring in parallel shear bands lying on {115} planes.
      We have studied the influence of temperature and axial orientation of nanowires.
      The observations are consistent with a martensitic phase transformation, but the
      finding leads to clear evidence of a different mechanism of deformation-induced
      phase transformation in Si nanowires with respect to their bulk counterpart. Our
      process provides a route to study shear-driven phase transformation at the
      nanoscale in Si.

PMID- 29328053
TI  - Symmetric spin-orbit interaction in triple quantum dot and minimisation of spin
      orbit leakage in CNOT gate.
AB  - We analyse spin-orbit interaction in triple quantum dots and show that a
      symmetric spin-orbit Hamiltonian does not follow the standard form used in double
      quantum dots, as a consequence of the presence of the third dot in the setup.
      Furthermore, CNOT implementation schemes based on the exchange interaction were
      studied. It was shown that an antisymmetric Dzyaloshinsky-Moriya term is the
      dominant source of spin-orbit leakage from the computational space. We present a
      simple scheme for the minimisation of leakage that can be implemented in cases
      where interacting spins enclose parallelogram or equilateral triangle loops.

PMID- 29328054
TI  - Effect of conductance linearity and multi-level cell characteristics of TaOx
      based synapse device on pattern recognition accuracy of neuromorphic system.
AB  - To improve the classification accuracy of an image data set (CIFAR-10) by using
      analog input voltage, synapse devices with excellent conductance linearity (CL)
      and multi-level cell (MLC) characteristics are required. We analyze the CL and
      MLC characteristics of TaOx-based filamentary resistive random access memory
      (RRAM) to implement the synapse device in neural network hardware. Our findings
      show that the number of oxygen vacancies in the filament constriction region of
      the RRAM directly controls the CL and MLC characteristics. By adopting a Ta
      electrode (instead of Ti) and the hot-forming step, we could form a dense
      conductive filament. As a result, a wide range of conductance levels with CL is
      achieved and significantly improved image classification accuracy is confirmed.

PMID- 29328055
TI  - An analysis of radon levels in the basements of UK workplaces and review of when
      employers should test.
AB  - Radon is a recognised lung carcinogen. The main source of radon in UK buildings
      is the ground. As basements have more ground contact than other parts of a
      building, and often limited ventilation, there is increased potential for high
      radon levels to occur. Regulations are in place in the UK to control radon
      exposure at work, to prompt employers to undertake risk assessments, test where
      necessary and take action if levels exceed certain thresholds. Both Public Health
      England (PHE) and the Health and Safety Executive (HSE) currently advise
      employers to test routinely occupied basements for radon, irrespective of
      geographical location; the minimum annual occupancy threshold has been
      established as one hour per week (approximately 50 h per year). PHE operates a
      routine measurement service for employers and holds the measurement data for
      radon levels in the basements of more than 3500 workplaces. Typically, radon
      concentrations follow a lognormal distribution over a wide range, when
      corrections are made for seasonal variations and the contribution of outside air.
      Statistical tests on these data show good correspondence in most cases for the
      workplace basements of seven different occupational sectors. Radon should be
      included in the risk assessments of basements of all workplace types irrespective
      of the radon-affected area status (i.e. whether they are located in a
      geographical unit where higher proportions of houses or workplaces are likely to
      exceed their reference levels). As a consequence of this analysis, however,
      evidence is presented that supports a change in the existing protocols on when to
      test the radon levels in basements, if a more sophisticated approach were to be
      adopted taking into account the affected area status.

PMID- 29328056
TI  - Monolithic Au/CeO2 nanorod framework catalyst prepared by dealloying for low
      temperature CO oxidation.
AB  - Monolithic Au/CeO2 nanorod frameworks (NFs) with porous structure were prepared
      by dealloying melt-spun Al89.7Ce10Au0.3 ribbons. After calcination in O2, a 3D
      Au/CeO2 NF catalyst with large surface area was obtained and used for low
      temperature CO oxidation. The small Au clusters/nanoparticles (NPs) were in situ
      supported and highly dispersed on the nanorod surface, creating many nanoscale
      contact interfaces. XPS results demonstrated that high-concentration oxygen
      vacancy and Au delta+/Au0 co-existed in the calcined sample. The Au/CeO2 nanorod
      catalyst calcined at 400  degrees C exhibited much higher catalytic activity for
      CO oxidation compared with the dealloyed sample and bare CeO2 nanorods. Moreover,
      its complete reaction temperature was as low as 91  degrees C. The designed
      Au/CeO2 NF catalyst not only possessed extreme sintering resistance but also
      exhibited high performance owing to the enhanced interaction between the Au
      clusters/NPs and CeO2 nanorod during calcination.

PMID- 29328057
TI  - Electron-phonon coupling from finite differences.
AB  - The interaction between electrons and phonons underlies multiple phenomena in
      physics, chemistry, and materials science. Examples include superconductivity,
      electronic transport, and the temperature dependence of optical spectra. A first
      principles description of electron-phonon coupling enables the study of the above
      phenomena with accuracy and material specificity, which can be used to understand
      experiments and to predict novel effects and functionality. In this topical
      review, we describe the first-principles calculation of electron-phonon coupling
      from finite differences. The finite differences approach provides several
      advantages compared to alternative methods, in particular (i) any underlying
      electronic structure method can be used, and (ii) terms beyond the lowest order
      in the electron-phonon interaction can be readily incorporated. But these
      advantages are associated with a large computational cost that has until recently
      prevented the widespread adoption of this method. We describe some recent
      advances, including nondiagonal supercells and thermal lines, that resolve these
      difficulties, and make the calculation of electron-phonon coupling from finite
      differences a powerful tool. We review multiple applications of the calculation
      of electron-phonon coupling from finite differences, including the temperature
      dependence of optical spectra, superconductivity, charge transport, and the role
      of defects in semiconductors. These examples illustrate the advantages of finite
      differences, with cases where semilocal density functional theory is not
      appropriate for the calculation of electron-phonon coupling and many-body methods
      such as the GW approximation are required, as well as examples in which higher
      order terms in the electron-phonon interaction are essential for an accurate
      description of the relevant phenomena. We expect that the finite difference
      approach will play a central role in future studies of the electron-phonon
      interaction.

PMID- 29328058
TI  - Behaviour of niobium during early Earth's differentiation: insights from its
      local structure and oxidation state in silicate melts at high pressure.
AB  - Niobium (Nb) is one of the key trace elements used to understand Earth's
      formation and differentiation, and is remarkable for its deficiency relative to
      tantalum in terrestrial rocks compared to the building chondritic blocks. In this
      context, the local environment of Nb in silica-rich melts and glasses is studied
      by in situ x-ray absorption spectroscopy (XAS) at high pressure (P) up to 9.3 GPa
      and 1350 K using resistive-heating diamond-anvil cells. Nb is slightly less
      oxidized in the melt (intermediate valence between  +4 and  +5) than in the glass
      (+5), an effect evidenced from the shift of the Nb-edge towards lower energies.
      Changes in the pre-edge features are also observed between melt and glass states,
      consistently with the observed changes in oxidation state although likely
      enhanced by temperature (T) effects. The oxidation state of Nb is not affected by
      pressure neither in the molten nor glassy states, and remains constant in the
      investigated P-range. The Nb-O coordination number is constant and equal to
      [Formula: see text] below 5 GPa, and only progressively increases up to [Formula:
      see text] at 9.3 GPa, the maximum P investigated. If these findings were to
      similarly apply to basaltic melts, that would rule out the hypothesis of Nb/Ta
      fractionation during early silicate Earth's differentiation, thus reinforcing the
      alternative hypothesis of fractionation during core formation on reduced pre
      planetary bodies.

PMID- 29328059
TI  - A simple way to synthesis larger-scale Cu<sub>2</sub>O/Ag nanoflower for
      ultrasensitive surface-enhanced Raman scattering detection.
AB  - Here, we report a simple strategy to prepare highly sensitive surface-enhanced
      Raman spectroscopy (SERS) substrates based on Ag decorated Cu<sub>2</sub>O
      nanoparticles by combing two commom techniques, viz, thermal oxidation growth of
      Cu<sub>2</sub>O nanoparticles and magnetron sputtering fabrication of Ag
      nanopartilce film. Methylene blue was used as raman analyte for the SERS study,
      and the substrates fabricated under optimized conditions have very good
      sensitivity (analytical enhancement facor ~10<sup>8</sup>) , stablility and
      reproducibility. A linear dependence about the SERS intensities with the
      concentration was obtained with the R<sup>2</sup> value > 0.9. These excellent
      properties indicate that the substrate have great potential in the detection of
      biological and chemical substances.

PMID- 29328060
TI  - In vivo neutron activation analysis of bone manganese in workers.
AB  - OBJECTIVE: Manganese (Mn) is a neurotoxin. However, the impact of elevated,
      chronic Mn exposure is not well understood, partially due to the lack of a
      cumulative exposure biomarker. To address this gap, our group developed a compact
      in vivo neutron activation analysis (IVNAA) system to quantify Mn concentration
      in bone (MnBn). APPROACH: In this study, we used this system and determined MnBn
      among male Chinese workers and compared results to their blood Mn (MnB), a
      measure of recent exposure, and the years of employment, a measure of cumulative
      exposure. A cross-sectional study was conducted with 30 ferroalloy smelters
      (exposed) and 30 general manufacturing workers (controls). MnBn was assessed
      using IVNAA, MnB was measured with inductively coupled plasma mass spectrometry,
      and occupational history and demographics were obtained via questionnaire. Mn
      doped phantoms were used to generate a calibration curve; spectra from these
      phantoms were consistent with in vivo spectra. MAIN RESULTS: The median
      (interquartile range (IQR)) values for Mn biomarkers were 2.7 ug g-1 (7.2) for
      MnBn and 14.1 ug l-1 (4.0) for MnB. In regression models adjusted for age and
      education, the natural log transformed MnBn (ln(MnBn)) was significantly
      associated with the exposed/control status (beta  =  0.44, p  =  0.047) and years
      of employment (beta  =  0.05, p  =  0.002), but not with natural log transformed
      MnB (ln(MnB)) (beta  =  0.54, p  =  0.188). SIGNIFICANCE: Our results support the
      use of IVNAA to quantify MnBn and the use of MnBn as a biomarker of cumulative Mn
      exposure.

PMID- 29328061
TI  - Spontaneous nano-gap formation in Ag film using NaCl sacrificial layer for Raman
      enhancement.
AB  - We report the method of fabrication of nano-gaps (known as hot spots) in Ag thin
      film using a sodium chloride (NaCl) sacrificial layer for Raman enhancement. The
      Ag thin film (20-50 nm) on the NaCl sacrificial layer undergoes an interfacial
      reaction due to the AgCl formed at the interface during water molecule
      intercalation. The intercalated water molecules can dissolve the NaCl molecules
      at interfaces and form the ionic state of Na+ and Cl-, promoting the AgCl
      formation. The Ag atoms can migrate by the driving force of this interfacial
      reaction, resulting in the formation of nano-size gaps in the film. The surface
      enhanced Raman scattering activity of Ag films with nano-size gaps has been
      investigated using Raman reporter molecules, Rhodamine 6G (R6G).

PMID- 29328062
TI  - Cyanobacterial photosynthesis under sulfidic conditions: insights from the
      isolate Leptolyngbya sp. strain hensonii.
AB  - We report the isolation of a pinnacle-forming cyanobacterium isolated from a
      microbial mat covering the sediment surface at Little Salt Spring-a flooded
      sinkhole in Florida with a perennially microoxic and sulfidic water column. The
      draft genome of the isolate encodes all of the enzymatic machinery necessary for
      both oxygenic and anoxygenic photosynthesis, as well as genes for methylating
      hopanoids at the C-2 position. The physiological response of the isolate to H2S
      is complex: (i) no induction time is necessary for anoxygenic photosynthesis;
      (ii) rates of anoxygenic photosynthesis are regulated by both H2S and irradiance;
      (iii) O2 production is inhibited by H2S concentrations as low as 1 MUM and the
      recovery rate of oxygenic photosynthesis is dependent on irradiance; (iv) under
      the optimal light conditions for oxygenic photosynthesis, rates of anoxygenic
      photosynthesis are nearly double those of oxygenic photosynthesis. We hypothesize
      that the specific adaptation mechanisms of the isolate to H2S emerged from a
      close spatial interaction with sulfate-reducing bacteria. The new isolate,
      Leptolyngbya sp. strain hensonii, is not closely related to other well
      characterized Cyanobacteria that can perform anoxygenic photosynthesis, which
      further highlights the need to characterize the diversity and biogeography of
      metabolically versatile Cyanobacteria. The isolate will be an ideal model
      organism for exploring the adaptation of Cyanobacteria to sulfidic conditions.

PMID- 29328065
TI  - Upper lid ptosis surgery: what is the optimal interval for the postoperative
      review? A retrospective review of 300 cases.
AB  - PurposeCorrection of upper eyelid ptosis is one of the most commonly performed
      oculoplastic procedures on the NHS but there is currently no data in the
      literature informing the surgeon of the optimal time for the first postoperative
      review. Our aim was to investigate how often a complication that warranted
      intervention occurred in the first 6 weeks after surgery and whether such a
      complication could have been predicted preoperatively.Patients and methodsA
      retrospective review was performed of 300 operations in 239 patients over a 9
      month period at Moorfields Eye Hospital, London. Electronic medical record
      software was used to extract data regarding the timing of first postoperative
      review, complications, any return to theatre, and any underlying risk factors or
      co-morbidities.ResultsAt 1 week 44 % (133) cases were reviewed, 30% (89) at 2
      weeks, 17% (50) at 3 weeks, and 9% (28) at 4 or more weeks. The overall
      complication rate at any time during the 6-week follow-up interval was 8%. The
      majority of these complications were minor (24 eyes, 8%) and 1 was major (0.3%).
      Of the 25 complications, an underlying risk factor was identified in 14
      cases.ConclusionsThese data indicate that postoperative complications are very
      low in the absence of preoperative risk factors. In our institution, as the risk
      of overcorrection is low, most patients without risk factors for exposure (51% in
      this series) can safely be reviewed later than 1 week after surgery, but for
      those with risk factors earlier follow-up is warranted.

PMID- 29328064
TI  - South African Eye Study (SAES): ethnic differences in central corneal thickness
      and intraocular pressure.
AB  - PurposeGlaucoma is the leading cause of irreversible blindness worldwide. South
      Africa has a diverse population but there is a lack of published ethnic specific
      normative data. The purpose of the study is to determine the distribution of
      intraocular pressure (IOP) and central corneal thickness (CCT) values in a multi
      ethnic South African population and to determine additional systemic and ocular
      factors that influence IOP and CCT.Patients and methodsThis cross-sectional study
      included a total of 402 participants with 706 eyes aged 18-94 years. Participants
      underwent a standardized interviewer-administered questionnaire for risk factor
      assessment followed by a full ophthalmic examination. The averages of six IOP
      readings were measured with an Icare PRO tonometer and CCT was measured with a
      Pentacam.ResultsThe mean CCT readings in the African, Mixed ethnicity, and
      Caucasian participants were 514.77+/-31.86, 531.77+/-35.17, and 549.97+/-30.51
      MUm (P<0.001). The mean IOP in the African, Mixed ethnicity, and Caucasian
      participants were 15.51+/-2.49, 15.09+/-2.12, and 15.13+/-2.53 mm Hg (P=0.07).
      Africans had significantly higher IOP than Mixed ethnicity (P=0.034) and
      Caucasians (P=0.011). Hypertensives had a higher IOP (P=0.03). Age and
      pseudophakia were associated with a lower IOP (P<0.001) and higher CCT (P<0.001).
      There was a strongly positive correlation between CCT and IOP (beta=0.021;
      P<0.001).ConclusionsIn the South African Eye Study (SAES), Africans had the
      thinnest corneas and highest IOP followed by Mixed ethnicity and Caucasians.
      Including systemic and ocular factors that influence IOP specific to each
      population and ethnic group, will lead to a more accurate clinical risk
      stratification in glaucoma management.

PMID- 29328063
TI  - Immune loss as a driver of coexistence during host-phage coevolution.
AB  - Bacteria and their viral pathogens face constant pressure for augmented immune
      and infective capabilities, respectively. Under this reciprocally imposed
      selective regime, we expect to see a runaway evolutionary arms race, ultimately
      leading to the extinction of one species. Despite this prediction, in many
      systems host and pathogen coexist with minimal coevolution even when well-mixed.
      Previous work explained this puzzling phenomenon by invoking fitness tradeoffs,
      which can diminish an arms race dynamic. Here we propose that the regular loss of
      immunity by the bacterial host can also produce host-phage coexistence. We pair a
      general model of immunity with an experimental and theoretical case study of the
      CRISPR-Cas immune system to contrast the behavior of tradeoff and loss mechanisms
      in well-mixed systems. We find that, while both mechanisms can produce stable
      coexistence, only immune loss does so robustly within realistic parameter ranges.

PMID- 29328066
TI  - A British Ophthalmological Surveillance Unit Study on metastatic endogenous
      endophthalmitis.
AB  - PurposeEndogenous endophthalmitis (EE) is a rare but serious ocular infection
      caused by the seeding of bacteria into the eye from a source elsewhere in the
      body. Studies suggest that EE accounts for 2 to 8% of all
      endophthalmitis.MethodsA prospective observational study was conducted using the
      British Ophthalmological Surveillance Unit reporting system. Questionnaires were
      sent to reporting Ophthalmologists in the UK to assess incidence, underlying
      aetiology, eye findings, management, and final outcomes in endogenous
      endophthalmitis over a 12-month period within the British Isles.ResultsSixty two
      cases reported with 48 initial questionnaires returned and 25 6-month follow-up
      questionnaires returned. The median age of patients affected was 57 years with
      youngest aged 2 years and oldest aged 85 years. Twenty three were male and 24
      were female. The median visual acuity in the affected eye was 3 logMAR (range 
      0.1 to 5). Blood cultures were taken in 36 patients, 58% of which were positive.
      Vitreous biopsy was taken in 35 patients, 23% of which were culture positive. The
      visual function as assessed by visual acuity had significantly improved at 6
      months with a median acuity of 0.18 logMAR (P=0.003).ConclusionsThe survey
      demonstrates the severe nature of endogenous endophthalmitis in patients with
      active infection or with risk factors for infection. Our study has demonstrated
      that at least half of the patients who were treated had significant vision
      improvement.

PMID- 29328067
TI  - A physical approach to model occlusions in the retinal microvasculature.
AB  - Blood occlusions in the retinal microvasculature contribute to the pathology of
      many disease states within the eye. These events can cause haemorrhaging and
      retinal detachment, leading to a loss of vision in the affected patient. Here, we
      present a physical approach to characterising the collective cell dynamics
      leading to plug formation, through the use of a bespoke microfluidic device, and
      through the derivation of a probabilistic model. Our microfluidic device is based
      on a filtration design that can tune the particle volume fraction of a flowing
      suspension within a conduit, with sizes similar to arterioles. This allows us to
      control and reproduce an occlusive event. The formation of the occlusion can be
      examined through the extracted motion of particles within the channel, which
      enables the assessment of individual and collective particle dynamics in the time
      leading to the clogging event. In particular, we observe that at the onset of the
      occlusion, particles form an arch bridging the channel walls. The data presented
      here inform the development of our mathematical model, which captures the
      essential factors promoting occlusions, and notably highlights the central role
      of adhesion in these processes. Both the physical and probabilistic models rely
      on significant approximations, and future investigation will seek to assess these
      approximations, including the deformability and complex flow profiles of the
      blood constituents. However, we anticipate that the general mechanisms of
      occlusion may be elucidated from these simple models. As microvascular flows in
      the eye can now be measured in vivo and non-invasively with single cell
      resolution, our model will also be compared to the pathophysiological
      characteristics of the human microcirculation.

PMID- 29328068
TI  - Indications for explant of implantable collamer lens.

PMID- 29328069
TI  - Inhibition of MUC1 biosynthesis via threonyl-tRNA synthetase suppresses
      pancreatic cancer cell migration.
AB  - Mucin1 (MUC1), a heterodimeric oncoprotein, containing tandem repeat structures
      with a high proportion of threonine, is aberrantly overexpressed in many human
      cancers including pancreatic cancer. Since the overall survival rate of
      pancreatic cancer patients has remained low for several decades, novel
      therapeutic approaches are highly needed. Intestinal mucin has been known to be
      affected by dietary threonine supply since de novo synthesis of mucin proteins is
      sensitive to luminal threonine concentration. However, it is unknown whether
      biosynthesis of MUC1 is regulated by threonine in human cancers. In this study,
      data provided suggests that threonine starvation reduces the level of MUC1 and
      inhibits the migration of MUC1-expressing pancreatic cancer cells. Interestingly,
      knockdown of threonyl-tRNA synthetase (TRS), an enzyme that catalyzes the
      ligation of threonine to its cognate tRNA, also suppresses MUC1 levels but not
      mRNA levels. The inhibitors of TRS decrease the level of MUC1 protein and
      prohibit the migration of MUC1-expressing pancreatic cancer cells. In addition, a
      positive correlation between TRS and MUC1 levels is observed in human pancreatic
      cancer cells. Concurrent with these results, the bioinformatics data indicate
      that co-expression of both TRS and MUC1 is correlated with the poor survival of
      pancreatic cancer patients. Taken together, these findings suggest a role for TRS
      in controlling MUC1-mediated cancer cell migration and provide insight into
      targeting TRS as a novel therapeutic approach to pancreatic cancer treatment.

PMID- 29328070
TI  - Nerve growth factor upregulates sirtuin 1 expression in cholestasis: a potential
      therapeutic target.
AB  - This study investigated the regulatory role of nerve growth factor (NGF) in
      sirtuin 1 (SIRT1) expression in cholestatic livers. We evaluated the expression
      of NGF and its cognate receptors in human livers with hepatolithiasis and the
      effects of NGF therapy on liver injury and hepatic SIRT1 expression in a bile
      duct ligation (BDL) mouse model. Histopathological and molecular analyses showed
      that the hepatocytes of human diseased livers expressed NGF, proNGF (a precursor
      of NGF), TrkA and p75NTR, whereas only p75NTR was upregulated in hepatolithiasis,
      compared with non-hepatolithiasis livers. In the BDL model without NGF therapy,
      p75NTR, but not TrkA antagonism, significantly deteriorated BDL-induced liver
      injury. By contrast, the hepatoprotective effect of NGF was abrogated only by
      TrkA and not by p75NTR antagonism in animals receiving NGF therapy. Intriguingly,
      a positive correlation between hepatic SIRT1 and NGF expression was found in
      human livers. In vitro studies demonstrated that NGF upregulated SIRT1 expression
      in mouse livers and human Huh-7 and rodent hepatocytes. Both NGF and proNGF
      induced protective effects against hydrogen peroxide-induced cytotoxicity in Huh
      7 cells, whereas inhibition of TrkA and p75NTR activity prevented oxidative cell
      death. Mechanistically, NGF, but not proNGF, upregulated SIRT1 expression in
      human Huh-7 and rodent hepatocytes via nuclear factor (NF)-kappaB activity,
      whereas NGF-induced phosphoinositide-3 kinase/Akt, extracellular signal-regulated
      kinase and NF-kappaB signaling and SIRT1 activity were involved in its
      hepatoprotective effects against oxidative injury. These findings suggest that
      pharmacological manipulation of the NGF/SIRT1 axis might serve as a novel
      approach for the treatment of cholestatic disease.

PMID- 29328073
TI  - Introduction to electromagnetic scattering: tutorial.
AB  - In this paper, an introduction to electromagnetic scattering is presented. We
      introduce the basic concepts needed to face a scattering problem, including the
      scattering, absorption, and extinction cross sections. We define the vector
      harmonics and we present some of their properties. Finally, we tackle the two
      canonical problems of the scattering by an infinitely long circular cylinder, and
      by a sphere, showing that the introduction of the vector wave function makes the
      imposition and solution of the boundary conditions particularly simple.

PMID- 29328074
TI  - Needles of light produced with a quasi-parabolic mirror.
AB  - We propose a quasi-parabolic mirror that can produce a long needle of light by
      focusing a radially polarized annular beam. The quasi-parabolic mirror can be
      acquired by moving the axis of rotation of a parabolic mirror. Using the extended
      Richards-Wolf theory for axisymmetric surfaces, we calculated that the needle
      obtained can have a longitudinal FWHM over hundreds to thousands of wavelengths
      by keeping the transverse FWHM under 0.36lambda. The consistent expression of the
      approximate relationship between the angular thickness of the incident beam and
      the longitudinal FWHM based on both geometrical optics and wave optics is
      presented.

PMID- 29328071
TI  - Sumoylation of histone deacetylase 1 regulates MyoD signaling during myogenesis.
AB  - Sumoylation, the conjugation of a small ubiquitin-like modifier (SUMO) protein to
      a target, has diverse cellular effects. However, the functional roles of the SUMO
      modification during myogenesis have not been fully elucidated. Here, we report
      that basal sumoylation of histone deacetylase 1 (HDAC1) enhances the
      deacetylation of MyoD in undifferentiated myoblasts, whereas further sumoylation
      of HDAC1 contributes to switching its binding partners from MyoD to Rb to induce
      myocyte differentiation. Differentiation in C2C12 skeletal myoblasts induced new
      immunoblot bands above HDAC1 that were gradually enhanced during differentiation.
      Using SUMO inhibitors and sumoylation assays, we showed that the upper band was
      caused by sumoylation of HDAC1 during differentiation. Basal deacetylase activity
      was not altered in the SUMO modification-resistant mutant HDAC1 K444/476R (HDAC1
      2R). Either differentiation or transfection of SUMO1 increased HDAC1 activity
      that was attenuated in HDAC1 2R. Furthermore, HDAC1 2R failed to deacetylate
      MyoD. Binding of HDAC1 to MyoD was attenuated by K444/476R. Binding of HDAC1 to
      MyoD was gradually reduced after 2 days of differentiation. Transfection of SUMO1
      induced dissociation of HDAC1 from MyoD but potentiated its binding to Rb. SUMO1
      transfection further attenuated HDAC1-induced inhibition of muscle creatine
      kinase luciferase activity that was reversed in HDAC1 2R. HDAC1 2R failed to
      inhibit myogenesis and muscle gene expression. In conclusion, HDAC1 sumoylation
      plays a dual role in MyoD signaling: enhancement of HDAC1 deacetylation of MyoD
      in the basally sumoylated state of undifferentiated myoblasts and dissociation of
      HDAC1 from MyoD during myogenesis.

PMID- 29328075
TI  - Digital Holography and 3D Imaging: introduction to the joint feature issue in
      Applied Optics and Journal of the Optical Society of America A.
AB  - The OSA Topical Meeting on Digital Holography and 3D Imaging (DH) was held 29 May
      to 1 June 2017 on Jeju Island, South Korea. Feature issues based on the DH
      meeting series have been released by Applied Optics (AO) since 2007. This year,
      AO and the Journal of the Optical Society of America A (JOSA A) jointly decided
      to have one such feature issue in each journal. This feature issue includes 33
      papers in AO and 9 in JOSA A and covers a large range of topics, reflecting the
      rapidly expanding techniques and applications of digital holography and 3D
      imaging. The upcoming DH meeting (DH 2018) will be held 25-28 June 2018 in
      Orlando, Florida, as part of the OSA Imaging and Applied Optics Congress.

PMID- 29328072
TI  - Immunomodulatory effect of CD200-positive human placenta-derived stem cells in
      the early phase of stroke.
AB  - Human placenta amniotic membrane-derived mesenchymal stem cells (AMSCs) regulate
      immune responses, and this property can be exploited to treat stroke patients via
      cell therapy. We investigated the expression profile of AMSCs cultured under
      hypoxic conditions and observed interesting expression changes in various genes
      involved in immune regulation. CD200, an anti-inflammatory factor and positive
      regulator of TGF-beta, was more highly expressed under hypoxic conditions than
      normoxic conditions. Furthermore, AMSCs exhibited inhibition of pro-inflammatory
      cytokine expression in co-cultures with LPS-primed BV2 microglia, and this effect
      was decreased in CD200-silenced AMSCs. The AMSCs transplanted into the ischemic
      rat model of stroke dramatically inhibited the expression of pro-inflammatory
      cytokines and up-regulated CD200, as compared with the levels in the sham-treated
      group. Moreover, decreased microglia activation in the boundary region and
      improvements in behavior were confirmed in AMSC-treated ischemic rats. The
      results suggested that the highly expressed CD200 from the AMSCs in a hypoxic
      environment modulates levels of inflammatory cytokines and microglial activation,
      thus increasing the therapeutic recovery potential after hypoxic-ischemic brain
      injury, and further demonstrated the immunomodulatory function of AMSCs in a
      stroke model.

PMID- 29328076
TI  - Analysis of 3D plasmonic circuits by using surface impedance models.
AB  - Novel and accurate global and local surface impedance models have been developed
      to analyze plasmonic circuits fast and efficiently. In the analysis procedure,
      first the metal strip in the plasmonic circuit is modeled by a surface impedance.
      Then, the calculated surface impedance is employed in the surface integral
      equation to analyze the plasmonic circuit such as a through line and line
      coupler. Accuracy of the numerical results is shown in comparison with a
      commercial simulation software. The number of unknowns as well as the
      computational time are also compared with the volume integral equation, and it is
      obvious that, using our proposed surface impedance models, the analysis will be
      much faster and more efficient. This could have been evident from the beginning
      because usage of the surface impedance model helps bring the unknowns to the
      boundary of the structure, which reduces the number of unknowns.

PMID- 29328077
TI  - Computational multispectral video imaging [Invited].
AB  - Multispectral imagers reveal information unperceivable to humans and conventional
      cameras. Here, we demonstrate a compact single-shot multispectral video-imaging
      camera by placing a micro-structured diffractive filter in close proximity to the
      image sensor. The diffractive filter converts spectral information to a spatial
      code on the sensor pixels. Following a calibration step, this code can be
      inverted via regularization-based linear algebra to compute the multispectral
      image. We experimentally demonstrated spectral resolution of 9.6 nm within the
      visible band (430-718 nm). We further show that the spatial resolution is
      enhanced by over 30% compared with the case without the diffractive filter. We
      also demonstrate Vis-IR imaging with the same sensor. Because no absorptive color
      filters are utilized, sensitivity is preserved as well. Finally, the diffractive
      filters can be easily manufactured using optical lithography and replication
      techniques.

PMID- 29328078
TI  - Special ciphertext-only attack to double random phase encryption by plaintext
      shifting with speckle correlation.
AB  - In this paper, a special ciphertext-only attack (COA) scenario to the traditional
      double random phase encoding (DRPE) technique is proposed based on plaintext
      shifting. We assume the attacker can illegally manipulate the DRPE system to gain
      multiple ciphertexts from randomly shifted versions of the same plaintext. The
      plaintext image can be recovered when our proposed scenario is combined with a
      speckle correlation attacking method proposed in previous work. Simulation
      results demonstrate that our proposed scheme can successfully crack the DRPE
      system even when the speckle correlation method alone fails to work in the
      conventional single ciphertext scenario due to the small size of the plaintext
      image. The work in this paper reveals a severe security flaw of DRPE systems when
      minor position shifting of the plaintext occurs.

PMID- 29328079
TI  - High-resolution coherent x-ray diffraction imaging of metal-coated polymer
      microspheres.
AB  - Coherent x-ray diffraction imaging (CXDI) is becoming an important 3D
      quantitative microscopy technique, allowing structural investigation of a wide
      range of delicate mesoscale samples that cannot be imaged by other techniques
      like electron microscopy. Here we report high-resolution 3D CXDI performed on
      spherical microcomposites consisting of a polymer core coated with a triple layer
      of nickel-gold-silica. These composites are of high interest to the
      microelectronics industry, where they are applied in conducting adhesives as fine
      pitch electrical contacts-which requires an exceptional degree of uniformity and
      reproducibility. Experimental techniques that can assess the state of the
      composites non-destructively, preferably also while embedded in electronic chips,
      are thus in high demand. We demonstrate that using CXDI, all four different
      material components of the composite could be identified, with radii matching
      well to the nominal specifications of the manufacturer. Moreover, CXDI provided
      detailed maps of layer thicknesses, roughnesses, and defects such as holes, thus
      also facilitating cross-layer correlations. The side length of the voxels in the
      reconstruction, given by the experimental geometry, was 16 nm. The effective
      resolution enabled resolving even the thinnest coating layer of ~20  nm nominal
      width. We discuss critically the influence of the weak phase approximation and
      the projection approximation on the reconstructed electron density estimates,
      demonstrating that the latter has to be employed. We conclude that CXDI has
      excellent potential as a metrology tool for microscale composites.

PMID- 29328080
TI  - Subsurface metrology using scanning white light interferometry: absolute z
      coordinates deep inside displays.
AB  - Mobile devices with interactive displays are ubiquitous commodities. Efficient
      quality control (QC) drives competitiveness. Scanning white light interferometry
      imaging offers a fast and nondestructive tool for QC purposes. Relying on optical
      compensation and image stitching, one can rapidly and cost-effectively produce
      sharp 3D images of a display's inner structures with a few nanometers' accuracy
      along the z direction. As a practical example, 3D images of a mobile device
      display revealed 0.92+/-0.02  MUm height variation in the top glass assembly. The
      proposed method improves quality assurance methods of display manufacturing.

PMID- 29328081
TI  - Is QR code an optimal data container in optical encryption systems from an error
      correction coding perspective?
AB  - Quick response (QR) code has been employed as a data carrier for optical
      cryptosystems in many recent research works, and the error-correction coding
      mechanism allows the decrypted result to be noise free. However, in this paper,
      we point out for the first time that the Reed-Solomon coding algorithm in QR code
      is not a very suitable option for the nonlocally distributed speckle noise in
      optical cryptosystems from an information coding perspective. The average channel
      capacity is proposed to measure the data storage capacity and noise-resistant
      capability of different encoding schemes. We design an alternative 2D barcode
      scheme based on Bose-Chaudhuri-Hocquenghem (BCH) coding, which demonstrates
      substantially better average channel capacity than QR code in numerical simulated
      optical cryptosystems.

PMID- 29328082
TI  - Linear iterative near-field phase retrieval (LIPR) for dual-energy x-ray imaging
      and material discrimination.
AB  - Near-field x-ray refraction (phase) contrast is unavoidable in many lab-based
      micro-CT imaging systems. Quantitative analysis of x-ray refraction (a.k.a. phase
      retrieval) is in general an under-constrained problem. Regularizing assumptions
      may not hold true for interesting samples; popular single-material methods are
      inappropriate for heterogeneous samples, leading to undesired blurring and/or
      over-sharpening. In this paper, we constrain and solve the phase-retrieval
      problem for heterogeneous objects, using the Alvarez-Macovski model for x-ray
      attenuation. Under this assumption we neglect Rayleigh scattering and pair
      production, considering only Compton scattering and the photoelectric effect. We
      formulate and test the resulting method to extract the material properties of
      density and atomic number from single-distance, dual-energy imaging of both
      strongly and weakly attenuating multi-material objects with polychromatic x-ray
      spectra. Simulation and experimental data are used to compare our proposed method
      with the Paganin single-material phase-retrieval algorithm, and an innovative
      interpretation of the data-constrained modeling phase-retrieval technique.

PMID- 29328083
TI  - Topological charge measurement of concentric OAM states using the phase-shift
      method.
AB  - We proposed a method to measure orbital angular momentum (OAM) states by using a
      multi-zone pure phase grating with the phase-shift technique. In free-space
      optical communication systems, the topological charges (TCs) of concentric OAM
      beams are usually detected for decoding, since the diameter of the OAM beam
      relates to the transmission distance. Two typical concentric OAM beams,
      concentric Laguerre-Gaussian beams and perfect vortex beams, were generated as
      incident beams, and the diffraction patterns can be separated by implementing a
      pure phase grating in the Fourier plane of a 4-f system. By counting the
      corresponding diffraction fringes, we can identify the TCs of the two OAM states.
      The simulation results show that the diffraction angles of the concentric OAM
      beams can be controlled and two concentric OAM states can be measured
      simultaneously.

PMID- 29328084
TI  - Unified and accurate diffraction calculation between two concentric cylindrical
      surfaces.
AB  - A unified and accurate fast diffraction calculation between a pair of concentric
      cylindrical surfaces is proposed. Analysis of the obliquity factor shows that the
      physical meaning of it is the projection of the unit complex amplitude in the
      propagation direction onto the outer normal of the observation point. Therefore,
      a unified and accurate diffraction calculation formula for both inside-out and
      outside-in propagation models is achieved. Furthermore, it is accurately
      accelerated by a fast calculation method using fast Fourier transformation with a
      speed-up over 3.9*106, which is compared with the direct calculation method under
      resolution of 512*512 pixels. Through analysis and comparison, it is found that
      the computing error is significant in the approximate method of the inside-out
      propagation model, which releases the limitation of the ratios of the outer
      radius and the height to the inner radius of the cylinders. The simulation
      results are presented to verify the correctness and accuracy of our proposal.

PMID- 29328085
TI  - Reference-free metric for quantitative noise appraisal in holographic phase
      measurements.
AB  - This paper presents a reference-free metric for quantitative appraisal of de
      noising algorithms for phase measurements in digital holography. In the
      literature, quality metrics are not self-contained because they require a noise
      free reference phase fringe pattern in order to be computed. In practical
      situations, no exact phase is available to evaluate the quality of processing. In
      order to bypass such limitations, one needs a metric directly capable of
      providing information on how efficient the filtering is, without any help from
      any reference measurements and by only considering the measured available phase
      data. This paper presents a novel reference-free metric, called estimated phase
      error for quantitative appraisal of de-noising algorithms for noisy phase data
      processing. This metric is based on the computation of an estimator of the
      standard deviation of the phase error between data processed with an external
      algorithm and that from the evaluated algorithm. A benchmark, including 37
      different de-noising algorithms, demonstrates that the proposed metric is capable
      of producing the same rankings as those obtained with classical metrics,
      requiring a reference phase. Application to phase data from mechanical testing
      demonstrates that the ranking obtained from experimental phase data is similar to
      that obtained during the benchmarking with simulated data.

PMID- 29328086
TI  - Geometric optics of a refringent sphere illuminated by a point source: caustics,
      wavefronts, and zero phase-fronts for every rainbow "k" order.
AB  - This study relates to a refringent sphere illuminated by a point source placed at
      a distance h from its center; for h->infinity the light beam becomes parallel. A
      selection of variables, principally angular with the center of the sphere as a
      common point, allows a global, straightforward, and geometrically transparent way
      to the rays, caustics, and wavefronts, internal as well as external, for every k
      order, k being the number of internal reflections. One obtains compact formulas
      for generating the rays and the wavefronts.

PMID- 29328087
TI  - Theoretical modeling and design of photonic structures in zeolite nanocomposites
      for gas sensing. Part II: volume gratings.
AB  - The suitability of holographic structures fabricated in zeolite nanoparticle
      polymer composite materials for gas sensing applications has been investigated.
      Theoretical modeling of the sensor response (i.e., change in hologram readout due
      to a change in refractive index modulation or thickness as a result of gas
      adsorption) of different sensor designs was carried out using the Raman-Nath
      theory and Kogelnik's coupled wave theory. The influence of a range of parameters
      on the sensitivity of holographically recorded surface and volume photonic
      structures has been studied, namely, hologram geometry, hologram thickness and
      spatial frequency, reconstruction wavelength, and zeolite nanoparticle refractive
      index. From this, the optimum fabrication conditions for both surface and volume
      holographic gas sensor designs have been identified. Here in Part II, results
      from modeling of the influence of design on the sensor response of
      holographically recorded volume grating structures for gas sensing applications
      are reported.

PMID- 29328088
TI  - Determination of the optimum double-pass image through focus operators.
AB  - A set of autofocus operators (AFO) are assessed for their ability to determine
      the optimal double-pass image as well as their potential to detect the focus
      lines and the disc of least confusion in astigmatic eyes. Eight AFO and three
      optical quality parameters (OQP) often used to analyze double-pass aerial images
      were considered. To quantify the discriminative power of each AFO and OQP, a
      maximum discrimination (MD) parameter was proposed. Double-pass images were
      obtained from an artificial eye with an induced astigmatism (Cylinder: -1  D, 
      0.75  D, 0.75 D, 1 D) and without astigmatism (Sphere: 0.1 D) and from 19 eyes of
      subjects with different refractions. The MD values for the autofocus operators
      Tenengrad variance and Gray level local variance were the highest for the
      artificial eye with and without astigmatism. In the case of astigmatic eyes, the
      discrimination of the focus lines with the autofocus operator Tenengrad variance
      was better than with OQP.

PMID- 29328089
TI  - Generation of vector Bessel beams with diffractive phase elements based on the
      Jacobi-Anger expansion.
AB  - We report the design and optimization of a diffractive phase element whose phase
      modulation is derived from the Jacobi-Anger relation, which allows the
      simultaneous generation of multiple scalar Bessel beams of different integer
      orders. In addition, by the appropriate treatment of a couple of such Bessel
      beams, we generate a vector Bessel beam of arbitrary order m. This beam is
      constructed by the collinear superposition of the scalar Bessel beam modes of
      orders m-1 and m+1, with circular orthogonal polarizations. We demonstrate
      experimentally both the simultaneous generation of the multiple scalar Bessel
      beams and the generation of vector Bessel beams of orders m=0 and m=1. These
      tasks are performed in an optical setup based on a pixelated liquid-crystal
      spatial light modulator.

PMID- 29328090
TI  - Built-up index methods and their applications for urban extraction from Sentinel
      2A satellite data: discussion.
AB  - Several built-up indices have been proposed in the literature in order to extract
      the urban sprawl from satellite data. Given their relative simplicity and easy
      implementation, such methods have been widely adopted for urban growth
      monitoring. Previous research has shown that built-up indices are sensitive to
      different factors related to image resolution, seasonality, and study area
      location. Also, most of them confuse urban surfaces with bare soil and barren
      land covers. By gathering the existing built-up indices, the aim of this paper is
      to discuss some of their advantages, difficulties, and limitations. In order to
      illustrate our study, we provide some application examples using Sentinel 2A
      data.

PMID- 29328091
TI  - Iterative design of diffractive elements made of lossy materials.
AB  - Diffractive surface relief elements made of lossy materials exhibit phase
      dependent absorption, which not only reduces the efficiency but also distorts the
      signal if the surface profile is realized on the basis of a phase-only design. We
      introduce an extension of the iterative Fourier transform algorithm, which
      accounts for such phase-dependent absorption, and present examples of its
      application to the design of diffractive beam splitters. The operator required
      for taking absorption into account is chosen to maximize the efficiency of the
      found design.

PMID- 29328092
TI  - Talbot carpet at the transverse plane produced in the diffraction of plane wave
      from amplitude radial gratings.
AB  - We experimentally demonstrate and theoretically predict a new and unprecedented
      optical carpet that includes all the geometric shadow and far-field and near
      field diffraction patterns at the transverse plane in the diffraction from a
      radial grating illuminated by a plane wavefront. The main feature of using radial
      grating is the continuous change of the spatial period along the radial
      direction. Therefore, the geometric shadow, and the near-field and far-field
      diffraction regimes are mixed at various propagation distances, and the
      traditional definitions for the different diffraction regimes would not apply
      here. We show that for a given propagation distance, at a certain radial distance
      the shadow regime changes to the near-field regime and at another certain radial
      distance, the diffraction pattern changes from a near-field to a far-field case.

PMID- 29328093
TI  - Trajectories on the Poincare sphere of polarization states of a beam passing
      through a rotating linear retarder.
AB  - The emerging polarization states from a linearly polarized monochromatic light
      passing through a rotating linear quarter-wave plate have been characterized as
      the intersection curve of a cylinder and the Poincare sphere. But in the cases
      where the input polarization states are in general elliptical or circular and
      pass through a rotating linear retarder, the emerging polarization states produce
      trajectories that do not correspond to the intersection of a sphere with one
      cylinder. Hence, in this work, we present a full characterization of the
      trajectories on the Poincare sphere for monochromatic input beams with an
      arbitrary polarization state passing through a rotating linear retarder as the
      intersection curve of the Poincare sphere with a cone. Moreover, it is shown that
      these trajectories are characterized by their projection on the equator plane,
      having the form of limacon of Pascal (Pascal's snails).

PMID- 29328094
TI  - Matched and wideband flat lens antennas using symmetric graded dielectrics.
AB  - Matched and wideband flat lens antennas using a two-dimensional symmetric graded
      dielectric (SGD) are considered. An explicit relation for refractive index of
      this type of antenna is presented. This design relation is obtained in two steps.
      The variations of refractive index are determined first in the radial direction
      and then in the axial direction. Additionally, reflector-lens antennas are
      introduced using two-dimensional SGD. The validity of design methodology is
      verified by simulation.

PMID- 29328095
TI  - Experimental comparison of single-pixel imaging algorithms.
AB  - Single-pixel imaging (SPI) is a novel technique that captures 2D images using a
      photodiode, instead of conventional 2D array sensors. SPI has high signal-to
      noise ratio, wide spectral range, low cost, and robustness to light scattering.
      Various algorithms have been proposed for SPI reconstruction, including linear
      correlation methods, the alternating projection (AP) method, and compressive
      sensing (CS) based methods. However, there has been no comprehensive review
      discussing respective advantages, which is important for SPI's further
      applications and development. In this paper, we review and compare these
      algorithms in a unified reconstruction framework. We also propose two other SPI
      algorithms, including a conjugate gradient descent (CGD) based method and a
      Poisson maximum-likelihood-based method. Both simulations and experiments
      validate the following conclusions: to obtain comparable reconstruction accuracy,
      the CS-based total variation (TV) regularization method requires the fewest
      measurements and consumes the least running time for small-scale reconstruction,
      the CGD and AP methods run fastest in large-scale cases, and the TV and AP
      methods are the most robust to measurement noise. In a word, there are trade-offs
      in capture efficiency, computational complexity, and robustness to noise among
      different SPI algorithms. We have released our source code for non-commercial
      use.

PMID- 29328096
TI  - Approximate Bayesian computation techniques for optical characterization of
      nanoparticle clusters.
AB  - Characterization of nanoparticle aggregates from observed scattered light leads
      to a highly complex inverse problem. Even the forward model is so complex that it
      prohibits the use of classical likelihood-based inference methods. In this study,
      we compare four so-called likelihood-free methods based on approximate Bayesian
      computation (ABC) that requires only numeric simulation of the forward model
      without the need of evaluating a likelihood. In particular, rejection, Markov
      chain Monte Carlo, population Monte Carlo, and adaptive population Monte Carlo
      (APMC) are compared in terms of accuracy. In the current model, we assume that
      the nanoparticle aggregates are mutually well separated and made up of particles
      of same size. Filippov's particle-cluster algorithm is used to generate
      aggregates, and discrete dipole approximation is used to estimate scattering
      behavior. It is found that the APMC algorithm is superior to others in terms of
      time and acceptance rates, although all algorithms produce similar posterior
      distributions. Using ABC techniques and utilizing unpolarized light experiments
      at 266 nm wavelength, characterization of soot aggregates is performed with less
      than 2 nm deviation in nanoparticle radius and 3-4 deviation in number of
      nanoparticles forming the monodisperse aggregates. Promising results are also
      observed for the polydisperse aggregate with log-normal particle size
      distribution.

PMID- 29328097
TI  - Temperature dependence of Brewster's angle.
AB  - In this work, a dielectric at a finite temperature is modeled as an ensemble of
      identical atoms moving randomly around where they are trapped. Light reflection
      from the dielectric is then discussed in terms of atomic radiation. Specific
      calculation demonstrates that because of the atoms' thermal motion, Brewster's
      angle is, in principle, temperature-dependent, and the dependence is weak in the
      low-temperature limit. What is also found is that the Brewster's angle is nothing
      but a result of destructive superposition of electromagnetic radiation from the
      atoms.

PMID- 29328098
TI  - Demonstration of single-shot digital holography using a Bayesian framework.
AB  - In this paper, we present experimental results for image reconstruction, with
      isoplanatic phase-error correction, from single-shot digital holography data. We
      demonstrate the utility of using a model-based iterative reconstruction (MBIR)
      algorithm to jointly compute the maximum a posteriori estimates of the phase
      errors and the real-valued object reflectance function. Specifically, we show
      that the MBIR algorithm is robust to noise and phase errors over a range of
      conditions.

PMID- 29328099
TI  - Incoherent component of light scattered by a monolayer of spherical particles:
      analysis of angular distribution and absorption of light.
AB  - We have derived an analytical solution for an incoherent component of light
      scattered by a normally illuminated monolayer of homogeneous spherical particles.
      It is based on the quasi-crystalline approximation of the theory of multiple
      scattering of waves as well as on the multipole expansion of electromagnetic
      fields and tensor Green's function in terms of vector spherical wave functions.
      We apply the solution to a description of scattering and absorption
      characteristics of partially ordered monolayers and monolayers with imperfect
      lattices. The impact of particle size and type of particle spatial order on light
      absorption is studied. The comparison of calculated and available experimental
      data is made on the angular and spectral position of the first diffraction order
      peak for a monolayer with an imperfect triangular lattice from silicon dioxide
      particles. The theoretical and experimental data are in close agreement.

PMID- 29328100
TI  - High-Q all-dielectric thermal emitters for mid-infrared gas-sensing applications.
AB  - A simple all-dielectric thermal emitter unit cell for narrowband gas-sensing
      application is proposed, providing large Q-factors compared to its plasmonic
      counterpart. It consists of a high-index dielectric-based elliptical puck on top
      of a back-reflector, providing narrowband thermal emission. Using full-wave
      simulations, it is demonstrated that the achievable Q-factors in this structure
      are orders of magnitude larger than what have been shown for plasmonic cells,
      thanks to their low-loss electrical characteristics. Furthermore, the thermal
      emission properties can be engineered by manipulating the geometry of the unit
      cell, whereby it is shown that these unit cells can provide polarized thermal
      emission simultaneously in two separate frequency bands, with identical Q-factor
      characteristics, depending on their ellipticity parameter.

PMID- 29328101
TI  - Precision of proportion estimation with binary compressed Raman spectrum.
AB  - The precision of proportion estimation with binary filtering of a Raman spectrum
      mixture is analyzed when the number of binary filters is equal to the number of
      present species and when the measurements are corrupted with Poisson photon
      noise. It is shown that the Cramer-Rao bound provides a useful methodology to
      analyze the performance of such an approach, in particular when the binary
      filters are orthogonal. It is demonstrated that a simple linear mean square error
      estimation method is efficient (i.e., has a variance equal to the Cramer-Rao
      bound). Evolutions of the Cramer-Rao bound are analyzed when the measuring times
      are optimized or when the considered proportion for binary filter synthesis is
      not optimized. Two strategies for the appropriate choice of this considered
      proportion are also analyzed for the binary filter synthesis.

PMID- 29328102
TI  - A new year, new editors, and new honors: editorial.
AB  - Editor-in-Chief P. Scott Carney congratulates recent awardees and introduces the
      Journal's newest Topical Editors.

PMID- 29328103
TI  - Mode diversity of weakly modulated cavity antennas.
AB  - The radiating mode of a cavity antenna at a particular frequency is fixed.
      However, by actively modulating the permittivity inside the cavity, the radiating
      mode may be changed. Using time-independent perturbation theory, we derive the
      modes of a cavity perturbed by many modulating elements. It is found that with a
      sufficient number of modulators of sufficient strength, the number of unique
      fields radiated by the cavity may reach a limit determined by the number of
      unperturbed cavity modes. The number of addressable radiated fields increases
      exponentially with the number of modulators; however, perturbations involving the
      interaction of several modulators become progressively weaker. For antennas at
      millimeter and terahertz frequencies, such cavity antennas can realize a great
      diversity of radiation patterns using fewer active devices, better exploiting the
      diversity achieved by each added modulator.

PMID- 29328104
TI  - Statistical properties of single-mode fiber coupling of satellite-to-ground laser
      links partially corrected by adaptive optics.
AB  - In the framework of satellite-to-ground laser downlinks, an analytical model
      describing the variations of the instantaneous coupled flux into a single-mode
      fiber after correction of the incoming wavefront by partial adaptive optics (AO)
      is presented. Expressions for the probability density function and the cumulative
      distribution function as well as for the average fading duration and fading
      duration distribution of the corrected coupled flux are given. These results are
      of prime interest for the computation of metrics related to coded transmissions
      over correlated channels, and they are confronted by end-to-end wave-optics
      simulations in the case of a geosynchronous satellite (GEO)-to-ground and a low
      earth orbit satellite (LEO)-to-ground scenario. Eventually, the impact of
      different AO performances on the aforementioned fading duration distribution is
      analytically investigated for both scenarios.

PMID- 29328105
TI  - Validity of ultrasound-guided aspiration needle biopsy in the diagnosis of
      micrometastases in sentinel lymph nodes in patients with cutaneous melanoma.
AB  - Background/Aim: Cutaneous melanoma is one of the most aggressive solid cancers,
      that develops local, regional and distant metastases. The presence of metastases
      in lymph nodes is in correlation with Breslow tumor thickness. According to
      various researches, in melanoma with more than 4 mm Breslow thickness, lymph node
      micrometastases can be found in 60-70% of cases. Sentinel lymph nodes biopsy is a
      diagnostic procedure for lymph node micrometastasis detection, which is necessary
      for disease staging. In recent studies, ultrasound-guided fine needle aspiration
      with cytology (US FNAC) of the sentinel lymph node was used as less invasive
      procedure, but is not accepted as the standard procedure. The goal of this work
      was to define sensitivity, specification and precision of the ultrasound-guided
      fine needle aspiration method in comparison with standard sentinel lymph node
      biopsy. Methods: After obtaining the Ethics Committee's permission, from 2012 to
      2014 a total of 60 patients with cutaneous melanoma were enrolled, and divided
      into three groups: group I with thin melanoma, group II with intermediate
      thickness melanoma and group III with thick melanoma. The presence of
      micrometastases in sentinel regional lymph nodes was analyzed by US FNAC. The
      results obtained were compared to sentinel lymph nodes biopsy (SLNB) results. The
      golden standard for calculating the specific, sensitive and precise
      characteristics of the method of US FNAC of sentinel lymph nodes was
      histopathologic lymph node examination of sentinel lymph nodes acquired through
      biopsy. Results: Detection rate of US FNAC was 0% in the group I, 5% in the group
      II and 30% in the group III. SLNB detection rates were: 10% in the group I, 15%
      in the group II, and 45% in the group III. In melanoma thicker than 4 mm, 15% of
      the patients were false negative by US FNAC. The sensitivity of US FNAC for all
      the patients was 50%: in the group I, 0%; in the group II, 33.3%; and in the
      group III, 66.6%. The method specificity for all examined patients was 100% and
      accuracy 88%: group I, 90%; group II, 90%; group III, 85%. The FNAC and SLNB
      micrometastasis detection rate was significantly higher in melanoma with Breslow
      thickness > 4 mm (group 3) in comparison to thin and intermediate thickness
      tumors. Conclusion: The method of ultrasound-guided fine needle aspiration of
      sentinel lymph nodes, according to its sensitivity, has a place in the
      diagnostics of micrometastasis in regional lymph nodes only in thick melanoma,
      but not in thin and intermediary thickness melanoma. The results must be
      confirmed in a larger number of patients. If this observation could be confirmed,
      it would rationalize treatment of patients with thick melanoma, decrease the
      number of operations and shorten the time to make the diagnosis.

PMID- 29328106
TI  - Polymer thermal optical switch for a flexible photonic circuit.
AB  - Flexible and wearable optoelectronic devices are the new trend for an active
      lifestyle. These devices are polymer-based for flexibility. We demonstrated
      flexible polymer waveguide optical switches for a flexible photonic integrated
      circuit. The optical switches are composed of a single-mode inverted waveguide
      with dimensions of 5 MUm waveguide width, 3 MUm ridge height, and 3 MUm slab
      height. A Mach-Zehnder structure was used in the device, with the Y-branch
      horizontal length of 0.1 cm, the distance between two heating branches of 30 MUm,
      and the heating branch length of 1 cm. The optical field of the device was
      simulated by beam propagation to optimize the electrode position. The switching
      properties of the flexible optical switch with different working conditions, such
      as contact to the polymer, silicon, and skin, were simulated. The device was
      prepared based on the photo curved polymer and lithography method. The end faces
      of the flexible film device were processed using an excimer laser with optimized
      parameters of 28  mJ/cm2 and 15 Hz. The response rise time and fall time on the
      PMMA substrate were measured as 1.98 ms and 2.71 ms, respectively. The power
      consumption was 16 mW and the extinction ratio was 11 dB. The response rise and
      fall times on the Si substrate were measured as 1.08 ms and 1.62 ms,
      respectively. The power consumption was 17 mW and the extinction ratio was 11 dB.
      The demonstrated properties indicate that this flexible optical waveguide
      structure can be used in the light control area of a wearable device.

PMID- 29328107
TI  - Modulation transfer function of liquid crystal microlenses and microprisms using
      double dielectric layer.
AB  - We investigate electrically tunable liquid crystal (LC) microlenses and
      microprisms based on double dielectric optically hidden (DDOH) layers.
      Comparative theoretical study of the spatial resolution limits in the creation of
      a spatially modulated electric field by the DDOH layer is conducted. Both the
      depth of the resulting optical phase modulation and its deviation from the
      desired wavefront are obtained for sine and sawtooth geometries of the DDOH
      layer's structure. A comparison is provided with the standard LC reorientation
      approach using patterned electrodes.

PMID- 29328108
TI  - Numerical simulation and design of an apodized diffractive optical element
      composed of open-ring zones and pinholes.
AB  - In this paper, we investigate the relationship between open-ring zones of the
      Fresnel zone plate and the pinhole rings of photon sieves (PSs). Numerical
      simulations show that the normalized diffraction fields near the focal point of
      an individual pinhole ring and the circular open-ring zone are the same. It is
      confirmed that the maximum diffraction efficiency of an open-ring zone is higher
      than that of the traditional pinhole ring. Meanwhile, pinhole rings have more
      flexibility for apodization filtering. Based on these key findings, we propose
      the design theory of an apodized diffractive optical element comprised of open
      ring zones and pinholes. To validate the theory, we developed a design example.
      Compared with traditional apodized PSs, the new apodized diffractive element has
      a 50.19% higher energy efficiency, and the minimum pinhole size is enlarged by
      30.77%.

PMID- 29328109
TI  - Distortion-compensated multifocusing of ultrashort pulse beams using cascade
      optical system.
AB  - We report a cascade optical system for multifocusing ultrashort pulse beams,
      particularly sub-50-fs pulses. System achromaticity is key to simultaneous
      compensation of the spatio-temporal pulse distortions. In this system,
      diffractive and refractive subsystems are optically coupled in cascade to correct
      chromatic aberrations, which are the primary cause of pulse distortion. We design
      a prototype system by applying achromatic conditions derived from an ABCD matrix
      analysis. The designed system is then evaluated using 20-fs pulses, by
      characterizing the transmitted pulses in terms of beam width and pulse duration;
      hence, the proposed distortion compensation scheme is validated. This pulse
      delivery system enables damage-free and high-throughput materials processing
      using ultrashort pulses.

PMID- 29328110
TI  - Modeling, simulation, and fabrication of bi-directional mode-division
      multiplexing for silicon-on-insulator platform.
AB  - A strip waveguide-based bi-directional mode-division multiplexer is proposed. A
      mathematical model has been proposed to analyze the performance, and the results
      are simulated. The design concept of this device to (de)multiplex three modes
      simultaneously has been studied previously for slab waveguides, both
      mathematically using the perturbative mode-coupled theory and by simulation using
      2D FDTD Solutions (FDTD, finite difference time domain). As slab waveguides are
      not suitable for extracting fabrication parameters for most silicon-on-insulator
      applications, we apply the concept to a more practical device that involves strip
      waveguides rather than slab waveguides. The effective index method (EIM) has been
      used to develop the mathematical model and to get approximate forms for both the
      profiles and coupling coefficients. The return loss of different modes is taken
      into consideration to fully characterize the device performance. Simple formulas
      for both insertion and return losses of all multiplexing modes have been derived.
      In addition, full vectorial 3D FDTD simulations are performed so as to validate
      our mathematical model. Different design parameters have been used to get
      numerical results of the proposed device. Our results reveal that the EIM has
      enough accuracy to characterize the performance of our device compared to that of
      the complex full vectorial simulation. In order to validate the used model, the
      device has been fabricated and tested. Good insertion losses and crosstalks for
      all modes have been obtained.

PMID- 29328111
TI  - Development of a spatially dispersed short-coherence interferometry sensor using
      diffraction grating orders: publisher's note.
AB  - This publisher's note amends the author listing and the funding and
      acknowledgment sections in Appl. Opt.57, 6391 (2017)APOPAI0003
      693510.1364/AO.56.006391.

PMID- 29328112
TI  - Design for a high birefringence photonic crystal fiber with multimode and low
      loss.
AB  - In this work, a novel design of a high birefringence photonic crystal fiber (HB
      PCF) with multimode and low confinement loss is proposed. To achieve high
      birefringence, the core is designed as an elliptical region, which is enclosed by
      twelve small holes. Based on this design, replacing the two circular holes at the
      top and bottom of the core region with two elliptical holes can further improve
      the birefringence. At the wavelength of 1.55 MUm, the birefringence of the
      fundamental mode (LP01) and the second-order mode (LP11) are 1.70*10-2 and
      1.85*10-2, respectively. Meanwhile, the confinement losses maintain on orders of
      1*10-5  dB/km (LP01) and 1*10-1  dB/km (LP11). After the effective refractive
      indices of two types of the proposed HB-PCF are calculated by the finite element
      method, the birefringence, confinement loss, bending loss, dispersion, and
      nonlinear coefficient are studied. These results reveal that the HB-PCF might be
      applied for polarization-maintaining and nonlinear optics.

PMID- 29328113
TI  - Spectroscopic study of a diffusion-bonded sapphire cell for hot metal vapors.
AB  - Characteristics of a diffusion-bonded sapphire cell for optical experiments with
      hot metal vapors were investigated. The sapphire cell consisted of sapphire
      crystal plates and a borosilicate-glass tube, which were bonded to each other by
      diffusion bonding without any binders or glues. The glass tube was attached to a
      vacuum manifold using the standard method applied in glass processing, filled
      with a small amount of Rb metal by chasing with a torch, and then sealed. The
      cell was baked at high temperatures, and optical experiments were then performed
      using rubidium atoms at room temperature. The sapphire cell was found to be
      vacuum tight, at least up to 350 degrees C, and the sapphire walls remained clear
      over all temperatures. From the optical experiments, the generation of a
      background gas was indicated after baking at 200 degrees C. The background gas
      pressure was low enough to avoid pressure broadening of absorption lines but high
      enough to cause velocity-changing collisions of Rb atoms. The generated gas
      pressure decreased at higher temperatures, probably due to chemical reactions.

PMID- 29328114
TI  - Sequences of the ranged amplitudes as a universal method for fast noninvasive
      characterization of SPAD dark counts.
AB  - Single-photon detectors based on avalanche photodiodes (SPADs) are key elements
      of many modern highly sensitive optical systems. One of the bottlenecks of such
      detectors is an afterpulsing effect, which limits detection rate and requires an
      optimal hold-off time. In this paper, we propose a novel approach for statistical
      analysis of SPAD dark counts, and we demonstrate its usefulness for the search of
      the experimental condition where the afterpulsing effect can be strongly
      eliminated. This approach exploits a sequence of ranked time intervals between
      the dark counts and does not contain a complex mathematical analysis of the
      experimental data. We show that the approach can be efficiently applied for a
      small number of the dark counts, and it seems to be very beneficial for practical
      fast characterization of SPAD devices.

PMID- 29328115
TI  - Digital Holography and 3D Imaging: introduction to the joint feature issue in
      Applied Optics and Journal of the Optical Society of America A.
AB  - The OSA Topical Meeting on Digital Holography and 3D Imaging (DH) was held 29 May
      to 1 June 2017 in Jeju Island, South Korea. Feature issues based on the DH
      meeting series have been released by Applied Optics (AO) since 2007. This year,
      AO and the Journal of the Optical Society of America A (JOSA A) jointly decided
      to have one such feature issue in each journal. This feature issue includes 33
      papers in AO and 9 in JOSA A and covers a large range of topics, reflecting the
      rapidly expanding techniques and applications of digital holography and 3D
      imaging. The upcoming DH meeting (DH 2018) will be held 25-28 June 2018 in
      Orlando, Florida, USA, as part of the OSA Imaging and Applied Optics Congress.

PMID- 29328116
TI  - Hybrid sensing face detection and registration for low-light and unconstrained
      conditions.
AB  - The capability to track, detect, and identify human targets in highly cluttered
      scenes under extreme conditions, such as in complete darkness or on the
      battlefield, has been one of the primary tactical advantages in military
      operations. In this paper, we propose a new collaborative, multi-spectrum sensing
      method to achieve face detection and registration under low-light and
      unconstrained conditions. We design and prototype a novel type of hybrid sensor
      by combining a pair of near-infrared (NIR) cameras and a thermal camera (a long
      wave infrared camera). We strategically surround each NIR sensor with a ring of
      LED IR flashes to capture the "red-eye," or more precisely, the "bright-eye"
      effect of the target. The "bright-eyes" are used to localize the 3D position of
      eyes and face. The recovered 3D information is further used to warp the thermal
      face imagery to a frontal-parallel pose so that additional tasks, such as face
      recognition, can be reliably conducted, especially with the assistance of
      accurate eye locations. Experiments on real face images are provided to
      demonstrate the merit of our method.

PMID- 29328117
TI  - Rotating of low-refractive-index microparticles with a quasi-perfect optical
      vortex.
AB  - Low-refractive-index microparticles, such as hollow microspheres, have shown
      great significance in some applications, such as biomedical sensing and targeted
      drug delivery. However, optical trapping and manipulation of low-refractive-index
      microparticles are challenging, owing to the repelling force exerted by typical
      optical traps. In this paper, we demonstrated optical trapping and rotating of
      large-sized low-refractive-index microparticles by using quasi-perfect optical
      vortex (quasi-POV) beams, which were generated by Fourier transform of high-order
      quasi-Bessel beams. Numerical simulation was carried out to characterize the
      focusing property of the quasi-POV beams. The dynamics of low-refractive-index
      microparticles in the quasi-POV with various topological charges was investigated
      in detail. To improve the trapping and rotating performances of the vortex, a
      point trap was introduced at the center of the ring. Experimental results showed
      that the quasi-POV was preferable for manipulation of large-sized low-refractive
      index microparticles, with its control of the particles' rotating velocity
      dependent only on the topological charge due to the unchanged orbital radius.

PMID- 29328118
TI  - Evaluation of the key design parameters of liquid crystal tunable lenses for
      depth-from-focus algorithm.
AB  - Liquid crystal (LC) tunable lenses have been extensively studied and used in
      various applications, however, most of them have been evaluated regardless of
      their optical imaging quality, in particular, concerning their intrinsic diffuse
      scattering. In this paper, we investigate the impact of such impairments when LC
      lenses are used as tunable elements in a depth-from-focus algorithm (DfF). We
      attempt to analyze these effects in order to design LC lenses that mitigate their
      impact on the imaging quality. For this purpose, we designed various lenses to
      evaluate several parameters such as optical, electrical, manufacturing, etc.,
      according to their implementations in a near-pixel DfF architecture.

PMID- 29328119
TI  - Standoff ultracompact micro-Raman sensor for planetary surface explorations.
AB  - We report the development of an innovative standoff ultracompact micro-Raman
      instrument that would solve some of the limitations of traditional micro-Raman
      systems to provide a superior instrument for future NASA missions. This active
      remote sensor system, based on a 532 nm laser and a miniature spectrometer, is
      capable of inspection and identification of minerals, organics, and biogenic
      materials within several centimeters (2-20 cm) at a high 10 MUm resolution. The
      sensor system is based on inelastic (Raman) light scattering and laser-induced
      fluorescence. We report on micro-Raman spectroscopy development and demonstration
      of the standoff Raman measurements by acquiring Raman spectra in daylight at a 10
      cm target distance with a small line-shaped laser spot size of 17.3 MUm (width)
      by 5 mm (height).

PMID- 29328120
TI  - Broadband perfect infrared absorption by tuning epsilon-near-zero and epsilon
      near-pole resonances of multilayer ITO nanowires.
AB  - We numerically investigate the broadband perfect infrared absorption by tuning
      epsilon-near-zero (ENZ) and epsilon-near-pole (ENP) resonances of multilayer
      indium tin oxide nanowires (ITO NWs). The monolayer ITO NWs array shows intensive
      absorption at ENZ and ENP wavelengths for p polarization, while only at the ENP
      wavelength for s polarization. Moreover, the ENP resonances are almost
      omnidirectional and the ENZ resonances are angularly dependent. Therefore, the
      absorption bandwidth is broader for p polarization than that for s polarization
      when polarized waves are incident obliquely. The ENZ resonances can be tuned by
      altering the doping concentration and volume filling factor of ITO NWs. However,
      the ENP resonances only can be tuned by changing the doping concentration of ITO
      NWs, and volume filling factor impacts little on the ENP resonances. Based on the
      strong absorption properties of each layer at their own ENP and ENZ resonances,
      the tuned absorption of the bilayer ITO NWs with the different doping
      concentrations can be broader and stronger. Furthermore, multilayer ITO NWs can
      achieve broadband perfect absorption by controlling the doping concentration,
      volume filling factor, and length of the NWs in each layer. This study has the
      potential to apply to applications requiring efficient absorption and energy
      conversion.

PMID- 29328121
TI  - High-precision rotation angle measurement method based on a lensless digital
      holographic microscope.
AB  - To accurately measure ultrasmall rotation angles, a robust and effective method
      based on lensless digital holographic microscopy is proposed in this paper. The
      method combines holographic microscopy, solid geometry, and 3D measurement,
      including holographic measurement and angle measurement processes. We can
      calculate the 3D shape by the angular spectrum algorithm and the least-squares
      phase-unwrapping algorithm in the holographic process. According to the
      relationship between the surface shape and rotation angles, the real-time
      rotation angles can be calculated. To validate the feasibility and practicability
      of the proposed approach, numerical noise simulations and experiments were
      performed. The measurement precision of rotation angle can reach 0.5" in the
      range of 1000" in this paper's experiments. The holographic method has high
      measurement precision and good stability. In addition, the compact small volume
      has great potential in small-angle sensor applications.

PMID- 29328122
TI  - Model-assisted measuring method for periodical sub-wavelength nanostructures.
AB  - This paper describes a scatterometry approach designed by simulations for the in
      line characterization of sub-wavelength sinusoidal gratings, which are formed on
      a transparent foil in a roll-to-roll procedure. Currently used methods are based
      on series of in situ measurements of the specular optical response at different
      incident angles or wavelengths for acquiring dimensional information on the
      gratings. The capability of single measurements of the first diffraction maxima
      at a fixed incident angle and wavelength to accurately measure the height of the
      sub-wavelength sinusoidal gratings is investigated in this work. The relation
      between the scattered powers of the diffraction maxima and the grating height is
      extracted from light scattering simulations, i.e., the inverse problem is solved.
      Optimal setup parameters for the measurement of grating heights ranging from 100
      nm to 300 nm are derived from simulations. Limits of measurability and the
      measurement uncertainty are evaluated for different instrumentation and
      simulation parameters. When using laser light in the visible wavelength range,
      the measurement uncertainty is physically limited by the photon shot noise to the
      picometer range, but the systematic contributions dominate the uncertainty. As a
      result, the measurement uncertainty for the grating height is estimated to <=12 
      nm, with a potential for <4  nm. Large-area scanning measurements performed
      offline and reference atomic force microscopy measurements verify the sensitivity
      of the presented measurement approach for identifying local variations of the
      spatial surface properties. Depending on the chosen detection system, sampling
      rates up to the MHz range are feasible, meeting the requirements of in-line
      process control of the roll-to-roll production process.

PMID- 29328123
TI  - On the fundamental comparison between unfocused and focused light field cameras.
AB  - Light field cameras have been extensively used in a variety of applications,
      thanks to their snapshot three-dimensional imaging capability. However, little is
      known regarding their pros and cons for a given application. Herein we report a
      fundamental comparison between two types of light field cameras-focused and
      unfocused. Our results indicate that the unfocused light field camera outperforms
      its focused counterpart in depth range and number of resolvable depth steps,
      while the focused light field camera has an edge in lateral resolution and
      reconstruction accuracy.

PMID- 29328124
TI  - Single-shot 3D topography of reflective samples with digital holographic
      microscopy.
AB  - In this work, an off-axis digital holographic microscope operating in reflection
      mode and a telecentric regimen to produce 3D topography of a microscopy sample is
      shown. The main characteristics of the proposed method, which make it different
      from the previous works in the field, are the possibility of producing the 3D
      topography by a single shot over the complete field of view with sensitivity of
      lambda/100, without phase perturbations introduced by the illuminating-imaging
      system, and with no further numerical processing beyond that required for
      recovering the phase map of the sample. A complete analysis of the illuminating
      imaging system of the digital holographic microscope is presented. The proposed
      digital holographic microscope is tested on imaging a USAF resolution test target
      and some micro-electromechanical systems (MEMs).

PMID- 29328125
TI  - Multispectral metasurface hologram at millimeter wavelengths.
AB  - We demonstrate a computer-generated metasurface hologram in which four distinct
      images are encoded at four different W-band (75-110 GHz) frequencies. The
      metasurface hologram consists of a planar array of resonant metamaterial elements
      excited by a collimated reference beam incident on the hologram at an oblique
      angle. Each of the images is encoded by a subset of metamaterial elements that
      are resonant at the specific excitation frequency and are spatially positioned to
      achieve a desired phase distribution in the plane in conjunction with the
      reference wave. The phase-only hologram is optimized using the Gerschberg-Saxton
      algorithm. The four well-defined images are produced at specific distances within
      the Fresnel zone of the aperture.

PMID- 29328126
TI  - Universal phase-depth mapping in a structured light field.
AB  - Technologies and devices for light field imaging have recently been developed for
      both industrial applications and scientific research to achieve excellent imaging
      properties. In our previous work, we combined light field imaging with structured
      illumination to propose a structured light field method in which multidirectional
      depth estimation can be performed for high-quality 3D imaging. However, the
      projection axis was implicitly assumed to be perpendicular to the reference
      plane, which is hard to meet in practice. In this paper, we derive a universal
      phase-depth mapping in a structured light field by relaxing this implicit
      condition. Both nonlinear and linear models were proposed based on this universal
      relationship. To test the model's practical performance, we simulated experiments
      by adding errors to the real measured values to evaluate the deviation in depth
      estimation. By comparing the root-mean-square distributions of the depth
      deviations with respect to the depth positions, we demonstrated that the
      nonlinear model was precise and consistent in a wide range of depth, and we
      employed this model to realize high-quality multidirectional scene
      reconstruction.

PMID- 29328127
TI  - Efficient method for fabricating a directional volumetric display using strings
      displaying multiple images.
AB  - In this study, we describe the fabrication of a high-resolution directional
      volumetric display that can display multiple images in different directions. The
      display designs can be used to show animations using strings; however, improving
      the resolution of such displays is difficult. Previously, the arrangement of
      strings has only been determined experimentally, making fabrication of volumetric
      displays a challenge. The goal of the present study is to improve resolution
      using simulations and to determine the arrangement of strings under three
      constraints. This simplified the fabrication of a directional volumetric display
      with 345 strings, which can display two different 20*20  pixel images in two
      different directions. A large high-resolution directional volumetric display can
      be fabricated using the proposed method. The string-type display has high
      artistic potential and is expected to find applications in the amusement and
      entertainment fields.

PMID- 29328128
TI  - Phase-locked optical metrology I: identification of intrinsic camera parameters
      from multiple grid views.
AB  - Camera-based optical metrology crucially relies on a proper identification of
      intrinsic (optical center position) and extrinsic (camera position) parameters of
      the used camera. A novel approach for processing phase data from multiple views
      of a target grid is presented, allowing these identifications within a pinhole
      camera model. First, the homography associated with the perspective distortion of
      each grid image is accurately identified using a phase-locking loop. Then, the
      affine transform for each view is determined, with the constraint of an identical
      set of intrinsic camera parameters. This requires slightly adjusting each
      homography. As there are highly redundant data, a criterion has to be chosen to
      optimize the result. The chosen criterion is the simultaneous minimization of the
      standard deviation between in-plane grid line displacements between the acquired
      grid images and the reconstructed ones. Experimental results demonstrate the
      efficiency of the method.

PMID- 29328129
TI  - Complex object wave extraction using time-multiplexing in off-axis digital
      holography.
AB  - In this paper, we present an algorithm for complex object wave extraction in off
      axis digital holography using a time-multiplexing and frequency spectrum-shifting
      technique. The proposed approach utilizes the digital time-multiplexing
      technique, in which two 90-deg-rotated off-axis holograms are recorded in
      sequence, and corresponding spectra are subtracted in the computed Fourier domain
      to eliminate the DC term. Then, the two subtracted holograms are digitally
      multiplexed into one complex hologram in the same plane, and by shifting the
      spatial frequency spectra of the subtracted hologram in the spatial frequency
      domain, one of the two cross-correlations can be obtained in the center. This
      technique simply extracts the spectrum of the real image in the frequency domain
      than the spatial filtering method.

PMID- 29328130
TI  - Quality of reconstruction of compressed off-axis digital holograms by frequency
      filtering and wavelets.
AB  - Compression of digital holograms can significantly help with the storage of
      objects and data in 2D and 3D form, its transmission, and its reconstruction.
      Compression of standard images by methods based on wavelets allows high
      compression ratios (up to 20-50 times) with minimum losses of quality. In the
      case of digital holograms, application of wavelets directly does not allow high
      values of compression to be obtained. However, additional preprocessing and
      postprocessing can afford significant compression of holograms and the acceptable
      quality of reconstructed images. In this paper application of wavelet transforms
      for compression of off-axis digital holograms are considered. The combined
      technique based on zero- and twin-order elimination, wavelet compression of the
      amplitude and phase components of the obtained Fourier spectrum, and further
      additional compression of wavelet coefficients by thresholding and quantization
      is considered. Numerical experiments on reconstruction of images from the
      compressed holograms are performed. The comparative analysis of applicability of
      various wavelets and methods of additional compression of wavelet coefficients is
      performed. Optimum parameters of compression of holograms by the methods can be
      estimated. Sizes of holographic information were decreased up to 190 times.

PMID- 29328131
TI  - Low-cost three-dimensional millimeter-wave holographic imaging system based on a
      frequency-scanning antenna.
AB  - In this paper, a closed-form two-dimensional reconstruction technique for hybrid
      frequency and mechanical scanning millimeter-wave (MMW) imaging systems is
      proposed. Although being commercially implemented in many imaging systems as a
      low-cost real-time solution, the results of frequency scanning systems have been
      reconstructed numerically or have been reported as the captured raw data with no
      clear details. Furthermore, this paper proposes a new framework to utilize the
      captured data of different frequencies for three-dimensional (3D) reconstruction
      based on novel proposed closed-form relations. The hybrid frequency and
      mechanical scanning structure, together with the proposed reconstruction method,
      yields a low-cost MMW imaging system with a satisfying performance. The extracted
      reconstruction formulations are validated through numerical simulations, which
      show comparable image quality with conventional MMW imaging systems, i.e.,
      switched-array (SA) and phased-array (PA) structures. Extensive simulations are
      also performed in the presence of additive noise, demonstrating the acceptable
      robustness of the system against system noise compared to SA and comparable
      performance with PA. Finally, 3D reconstruction of the simulated data shows a
      depth resolution of better than 10 cm with minimum degradation of lateral
      resolution in the 10 GHz frequency bandwidth.

PMID- 29328132
TI  - Digital hologram transformations for RGB color holographic display with
      independent image magnification and translation in 3D.
AB  - A new framework for in-plane transformations of digital holograms (DHs) is
      proposed, which provides improved control over basic geometrical features of
      holographic images reconstructed optically in full color. The method is based on
      a Fourier hologram equivalent of the adaptive affine transformation technique
      [Opt. Express18, 8806 (2010)OPEXFF1094-408710.1364/OE.18.008806]. The solution
      includes four elementary geometrical transformations that can be performed
      independently on a full-color 3D image reconstructed from an RGB hologram: (i)
      transverse magnification; (ii) axial translation with minimized distortion; (iii)
      transverse translation; and (iv) viewing angle rotation. The independent
      character of transformations (i) and (ii) constitutes the main result of the work
      and plays a double role: (1) it simplifies synchronization of color components of
      the RGB image in the presence of mismatch between capture and display parameters;
      (2) provides improved control over position and size of the projected image,
      particularly the axial position, which opens new possibilities for efficient
      animation of holographic content. The approximate character of the operations (i)
      and (ii) is examined both analytically and experimentally using an RGB circular
      holographic display system. Additionally, a complex animation built from a single
      wide-aperture RGB Fourier hologram is presented to demonstrate full capabilities
      of the developed toolset.

PMID- 29328133
TI  - Computer-generated hologram generation method to increase the field of view of
      the reconstructed image.
AB  - In this paper, a computer-generated hologram (CGH) generation method is proposed
      to increase the field of view (FOV) in the holographic display. The CGH is
      generated through accumulating interference patterns of all object points. The
      size of each interference pattern is equal to the sum of the size of the recorded
      object and the spatial light modulator (SLM), so the size of the interference
      pattern is increased. The position of the interference pattern is related to that
      of the corresponding recorded object point. In the reconstruction process, three
      SLMs in a planar configuration are used to load the CGH. The seams between the
      SLMs are eliminated by beam splitters. Meanwhile, the boundaries of the
      diffraction light of all interference patterns are parallel with each other.
      Compared with the holographic display method using one SLM, the experiments
      demonstrate that the proposed method can reduce the demand for viewing distance
      and expand the FOV obviously in the horizontal direction, especially for the
      large-sized recorded object.

PMID- 29328134
TI  - 360-degree color hologram generation for real 3D objects.
AB  - Recently, holographic display and computer-generated holograms calculated from
      real existing objects have been more actively investigated to support holographic
      video applications. In this paper, we proposed a method of generating 360-degree
      color holograms of real 3D objects in an efficient manner. 360-degree 3D images
      are generated using the actual 3D image acquisition system consisting of a depth
      camera and a turntable and intermediate view generation. Then, 360-degree color
      holograms are calculated using a viewing-window-based computer-generated
      hologram. We confirmed that floating 3D objects are faithfully reconstructed
      around a 360-degree direction using our 360-degree tabletop color holographic
      display.

PMID- 29328135
TI  - Autostereoscopic 3D display system with dynamic fusion of the viewing zone under
      eye tracking: principles, setup, and evaluation [Invited].
AB  - We study optical technologies for viewer-tracked autostereoscopic 3D display
      (VTA3D), which provides improved 3D image quality and extended viewing range. In
      particular, we utilize a technique-the so-called dynamic fusion of viewing zone
      (DFVZ)-for each 3D optical line to realize image quality equivalent to that
      achievable at optimal viewing distance, even when a viewer is moving in a depth
      direction. In addition, we examine quantitative properties of viewing zones
      provided by the VTA3D system that adopted DFVZ, revealing that the optimal
      viewing zone can be formed at viewer position. Last, we show that the comfort
      zone is extended due to DFVZ. This is demonstrated by a viewer's subjective
      evaluation of the 3D display system that employs both multiview autostereoscopic
      3D display and DFVZ.

PMID- 29328136
TI  - Beam shaping diffractive wave plates [Invited].
AB  - We present and discuss opportunities opened up by a new generation of beam
      shaping optical elements that combine capabilities of digital spatial light
      polarization converters and diffractive properties of thin liquid crystalline
      films with patterned orientation of anisotropy axis (diffractive wave plates).
      Several functions of the new generation beam shapers are demonstrated, among them
      converting a laser beam of a Gaussian profile into a ring profile in the far
      field, a flattop profile, and into complex images. We also describe electrically
      controlled beam shaping optical elements which can be turned off and on within
      milliseconds by applying a low external voltage. Optical, morphological, and
      electro-optical properties of the components are characterized.

PMID- 29328137
TI  - Hardware and software improvements to a low-cost horizontal parallax holographic
      video monitor.
AB  - Displays capable of true holographic video have been prohibitively expensive and
      difficult to build. With this paper, we present a suite of modularized hardware
      components and software tools needed to build a HoloMonitor with basic "hacker
      space" equipment, highlighting improvements that have enabled the total materials
      cost to fall to $820, well below that of other holographic displays. It is our
      hope that the current level of simplicity, development, design flexibility, and
      documentation will enable the lay engineer, programmer, and scientist to
      relatively easily replicate, modify, and build upon our designs, bringing true
      holographic video to the masses.

PMID- 29328138
TI  - Optical convolution for quantitative phase retrieval using the transport of
      intensity equation.
AB  - Propagation-based phase imaging using the transport of intensity equation (TIE)
      allows rapid, deterministic phase retrieval from defocused images. However,
      computational solutions to the TIE suffer from significant low-frequency noise
      artifacts and are unique up to the application of boundary conditions on the
      phase. We demonstrate that quantitative phase can be imaged directly at the
      detector for a class of pure-phase samples by appropriately patterning the
      illumination to solve the TIE through an optical convolution with the source.
      This can reduce noise artifacts, obviates the need for user-supplied boundary
      conditions and is demonstrated via simulation and experiment.

PMID- 29328139
TI  - Holographic display methods for volume data: polygon-based and MIP-based methods.
AB  - Volume data are widely used in many areas, especially in biomedical science and
      geology. However, current visualization technologies of volume data cannot
      satisfy the visual requirements of humans. In this study, we propose two
      holographic display methods for volume data. The first method is polygon-based,
      and the other is maximum intensity projection (MIP)-based. Both methods are able
      to generate computer generated holograms of volume data. The polygon-based method
      can obtain various and colorful holograms, while the MIP-based method can be
      quickly calculated. Both methods can generate holographic animations, which were
      displayed on an electro-holography device.

PMID- 29328140
TI  - Full-color digitized holography for large-scale holographic 3D imaging of
      physical and nonphysical objects.
AB  - Digitized holography techniques are used to reconstruct three-dimensional (3D)
      images of physical objects using large-scale computer-generated holograms (CGHs).
      The object field is captured at three wavelengths over a wide area at high
      densities. Synthetic aperture techniques using single sensors are used for image
      capture in phase-shifting digital holography. The captured object field is
      incorporated into a virtual 3D scene that includes nonphysical objects, e.g.,
      polygon-meshed CG models. The synthetic object field is optically reconstructed
      as a large-scale full-color CGH using red-green-blue color filters. The CGH has a
      wide full-parallax viewing zone and reconstructs a deep 3D scene with natural
      motion parallax.

PMID- 29328141
TI  - Improved particle position accuracy from off-axis holograms using a Chebyshev
      model.
AB  - Side scattered light from micrometer-sized particles is recorded using an off
      axis digital holographic setup. From holograms, a volume is reconstructed with
      information about both intensity and phase. Finding particle positions is non
      trivial, since poor axial resolution elongates particles in the reconstruction.
      To overcome this problem, the reconstructed wavefront around a particle is used
      to find the axial position. The method is based on the change in the sign of the
      curvature around the true particle position plane. The wavefront curvature is
      directly linked to the phase response in the reconstruction. In this paper we
      propose a new method of estimating the curvature based on a parametric model. The
      model is based on Chebyshev polynomials and is fit to the phase anomaly and
      compared to a plane wave in the reconstructed volume. From the model
      coefficients, it is possible to find particle locations. Simulated results show
      increased performance in the presence of noise, compared to the use of finite
      difference methods. The standard deviation is decreased from 3-39 MUm to 6-10 MUm
      for varying noise levels. Experimental results show a corresponding improvement
      where the standard deviation is decreased from 18 MUm to 13 MUm.

PMID- 29328142
TI  - Full field-of-view digital lens-free holography for weak-scattering objects based
      on grating modulation.
AB  - Grating-based single-shot digital lens-free holography with spatial spectral
      multiplexing is proposed to realize full field-of-view (FOV) imaging for weak
      scattering objects. Multiple object waves are generated by a one-dimensional
      grating that is placed in near contact with the object to avoid the cross talk
      among different diffraction orders during reconstruction. A multiplexed off-axis
      hologram is created by interference between the object waves and reference wave
      and captured by an image sensor in one shot. Multiple imaging areas corresponding
      to the captured object waves can be simultaneously retrieved during
      reconstruction. A formula which guarantees full FOV imaging without cross talk or
      information loss is presented. The imaging experiments of a USAF resolution
      target are presented to demonstrate the feasibility of this method.

PMID- 29328143
TI  - Resolution optimization of an off-axis lensless digital holographic microscope.
AB  - Microscopes aimed at detecting cellular life in extreme environments such as
      ocean-bearing solar system moons must provide high resolution in a compact,
      robust instrument. Here, we consider the resolution optimization of a compact off
      axis lensless digital holographic microscope (DHM) that consists of a sample
      placed between an input point-source pair and a detector array. Two optimal high
      resolution regimes are identified at opposite extremes-a low-magnification regime
      with the sample located near a small-pixel detector array, and a high
      magnification regime with the sample near the input plane. In the former,
      resolution improves with smaller pixels, while in the latter, the effect of the
      finite pixel size is obviated, and the spatial resolution improves with detector
      array size. Using an off-axis lensless DHM with a 2 k*2 k array of 5.5 MUm-pixels
      in the high-magnification regime, and standard aberration correction software, a
      resolution of ~0.95  MUm has been demonstrated, a factor of 5.8 smaller than the
      pixel size. Our analysis further suggests that with yet larger detector arrays, a
      lensless DHM should be capable of near wavelength-scale resolution.

PMID- 29328144
TI  - Error of image saturation in the structured-light method.
AB  - In the phase-measuring structured-light method, image saturation will induce
      large phase errors. Usually, by selecting proper system parameters (such as the
      phase-shift number, exposure time, projection intensity, etc.), the phase error
      can be reduced. However, due to lack of a complete theory of phase error, there
      is no rational principle or basis for the selection of the optimal system
      parameters. For this reason, the phase error due to image saturation is analyzed
      completely, and the effects of the two main factors, including the phase-shift
      number and saturation degree, on the phase error are studied in depth. In
      addition, the selection of optimal system parameters is discussed, including the
      proper range and the selection principle of the system parameters. The error
      analysis and the conclusion are verified by simulation and experiment results,
      and the conclusion can be used for optimal parameter selection in practice.

PMID- 29328145
TI  - Iterative pixelwise approach applied to computer-generated holograms and
      diffractive optical elements.
AB  - This paper presents a novel approach to optimizing the design of phase-only
      computer-generated holograms (CGH) for the creation of binary images in an
      optical Fourier transform system. Optimization begins by selecting an image pixel
      with a temporal change in amplitude. The modulated image function undergoes an
      inverse Fourier transform followed by the imposition of a CGH constraint and the
      Fourier transform to yield an image function associated with the change in
      amplitude of the selected pixel. In iterations where the quality of the image is
      improved, that image function is adopted as the input for the next iteration. In
      cases where the image quality is not improved, the image function before the
      pixel changed is used as the input. Thus, the proposed approach is referred to as
      the pixelwise hybrid input-output (PHIO) algorithm. The PHIO algorithm was shown
      to achieve image quality far exceeding that of the Gerchberg-Saxton (GS)
      algorithm. The benefits were particularly evident when the PHIO algorithm was
      equipped with a dynamic range of image intensities equivalent to the amplitude
      freedom of the image signal. The signal variation of images reconstructed from
      the GS algorithm was 1.0223, but only 0.2537 when using PHIO, i.e., a 75%
      improvement. Nonetheless, the proposed scheme resulted in a 10% degradation in
      diffraction efficiency and signal-to-noise ratio.

PMID- 29328146
TI  - Accurate shape measurement of focusing microstructures in Fourier digital
      holographic microscopy.
AB  - This paper proposes a measurement method of focusing objects with a high gradient
      shape of a small and large radius of curvature. The measurements are carried out
      on a Fourier digital holographic microscope with optimized illumination
      conditions maximizing the usage of the system's numerical aperture. The obtained
      fringe patterns are the result of interference of deformed spherical object and
      spherical reference waves. The key elements of the method are the aberration
      compensation and calibration procedures. They provide accurate reconstruction of
      the object wave and determination of the focus position of the sample. The shape
      is calculated in two steps. First, the object wave is reconstructed at the plane
      of the object focus using single or multiframe phase extraction algorithm and the
      specialized propagation method. The step includes compensation for spherical
      aberration. In the second step, the sample shape is computed with the local ray
      approximation approach. The proposed method is experimentally validated with
      measurements of challenging, high gradient shapes (convex, concave) of different
      radiuses of curvature.

PMID- 29328147
TI  - Optical diffraction tomography with fully and partially coherent illumination in
      high numerical aperture label-free microscopy [Invited].
AB  - Quantitative label-free imaging is an important tool for the study of living
      microorganisms that, during the last decade, has attracted wide attention from
      the optical community. Optical diffraction tomography (ODT) is probably the most
      relevant technique for quantitative label-free 3D imaging applied in wide-field
      microscopy in the visible range. The ODT is usually performed using spatially
      coherent light illumination and specially designed holographic microscopes.
      Nevertheless, the ODT is also compatible with partially coherent illumination and
      can be realized in conventional wide-field microscopes by applying refocusing
      techniques, as it has been recently demonstrated. Here, we compare these two ODT
      modalities, underlining their pros and cons and discussing the optical setups for
      their implementation. In particular, we pay special attention to a system that is
      compatible with a conventional wide-field microscope that can be used for both
      ODT modalities. It consists of two easily attachable modules: the first for
      sample illumination engineering based on digital light processing technology; the
      other for focus scanning by using an electrically driven tunable lens. This
      hardware allows for a programmable selection of the wavelength and the
      illumination design, and provides fast data acquisition as well. Its performance
      is experimentally demonstrated in the case of ODT with partially coherent
      illumination providing speckle-free 3D quantitative imaging.

PMID- 29328148
TI  - Fast occlusion processing for a polygon-based computer-generated hologram using
      the slice-by-slice silhouette method.
AB  - In a polygon-based computer-generated hologram (CGH), the three-dimensional (3D)
      model is represented as a polygon, which consists of numerous small facets.
      Lighting effect, material texture, and surface property can be included in the
      polygonal model, which enables polygon-based CGH to realize high-fidelity 3D
      display. On the other hand, the occlusion effect is an important depth cue for 3D
      display. In polygon-based CGH, however, occlusion processing is difficult and
      time-consuming work. In this paper, we proposed a simple and fast occlusion
      processing method, the slice-by-slice silhouette (S3) method, for generating the
      occlusion effect in polygon-based CGH. In the S3 method, the polygonal model is
      sliced into multiple thin segments. For each segment, a silhouette mask is
      generated and located at the backside of the segment. The incident light is first
      shaded by the mask and superimposes on the light emitted from the facets of the
      evaluated segment. In this way, every segment can be processed sequentially to
      get the resulting object light. Our experimental result demonstrates that the S3
      method can generate a high-definition hologram with qualified occlusion effect.
      The computing complexity of the S3 method is lower than that of previous methods.
      In addition, the S3 method can be parallelized easily, and thus can be further
      speeded up by applying a parallel computing framework, such as multi-core CPU or
      GPU.

PMID- 29328149
TI  - Evaluation of finite difference and FFT-based solutions of the transport of
      intensity equation.
AB  - A finite difference method is proposed for solving the transport of intensity
      equation. Simulation results show that although slower than fast Fourier
      transform (FFT)-based methods, finite difference methods are able to reconstruct
      the phase with better accuracy due to relaxed assumptions for solving the
      transport of intensity equation relative to FFT methods. Finite difference
      methods are also more flexible than FFT methods in dealing with different
      boundary conditions.

PMID- 29328150
TI  - Phase retrieval based on transport of intensity and digital holography.
AB  - We propose a technique in which intensity images are reconstructed from a digital
      hologram to provide inputs for the transport-of-intensity equation for unwrapped
      phase recovery. By doing this, we avoid shifting of the sample or the camera in
      the experiment, a method commonly employed while using the method of transport-of
      intensity equation for phase retrieval. Computer simulations as well as
      experimental results have been demonstrated to verify the effectiveness of the
      proposed idea. The underlying numerical technique can also be viewed as an
      alternative to existing phase-unwrapping algorithms.

PMID- 29328151
TI  - Characterization of the reference wave in a compact digital holographic camera.
AB  - A hologram is a recording of the interference between an unknown object wave and
      a coherent reference wave. Providing the object and reference waves are
      sufficiently separated in some region of space and the reference beam is known, a
      high-fidelity reconstruction of the object wave is possible. In traditional
      optical holography, high-quality reconstruction is achieved by careful
      reillumination of the holographic plate with the exact same reference wave that
      was used at the recording stage. To reconstruct high-quality digital holograms
      the exact parameters of the reference wave must be known mathematically. This
      paper discusses a technique that obtains the mathematical parameters that
      characterize a strongly divergent reference wave that originates from a fiber
      source in a new compact digital holographic camera. This is a lensless design
      that is similar in principle to a Fourier hologram, but because of the large
      numerical aperture, the usual paraxial approximations cannot be applied and the
      Fourier relationship is inexact. To characterize the reference wave, recordings
      of quasi-planar object waves are made at various angles of incidence using a
      Dammann grating. An optimization process is then used to find the reference wave
      that reconstructs a stigmatic image of the object wave regardless of the angle of
      incidence.

PMID- 29328153
TI  - Fast and high-resolution light field acquisition using defocus modulation.
AB  - In the conventional microlens-array-based light field imaging system, there is a
      trade-off between the angular and spatial resolutions. Light field reconstruction
      from images captured by focal plane sweeping, such as light field moment imaging
      (LFMI) and light field reconstruction with back projection (LFBP), can achieve
      high transverse resolution comparable to the modern camera sensor. However, the
      acquisition of a series of focal plane sweeping images along the optical axis is
      time consuming and requires fine alignment. Furthermore, different focal-plane
      based light field reconstruction techniques require images with different
      characteristics. To solve these problems, we present an efficient approach for
      fast light field acquisition with precise focal plane sweeping capture by defocus
      modulation, rather than mechanical movement. Also, we verify the validity and the
      improvement of our system. With the controllable point spread function, we can
      capture images for light field reconstruction with both LFMI and LFBP. Otherwise,
      we quantitatively compare the two methods using images captured with the proposed
      systems.

PMID- 29328152
TI  - Single-shot, dual-mode, water-immersion microscopy platform for biological
      applications.
AB  - A single-shot water-immersion digital holographic microscope combined with
      broadband (white light) illumination mode is presented. This double imaging
      platform allows conventional incoherent visualization with phase holographic
      imaging of inspected samples. The holographic architecture is implemented at the
      image space (that is, after passing the microscope lens), thus reducing the
      sensitivity of the system to vibrations and/or thermal changes in comparison to
      regular interferometers. Because of the off-axis holographic recording principle,
      quantitative phase images of live biosamples can be recorded in a single camera
      snapshot at full-field geometry without any moving parts. And, the use of water
      immersion imaging lenses maximizes the achievable resolution limit. This dual
      mode microscope platform is first calibrated using microbeads, then applied to
      the characterization of fixed cells (neuroblastoma, breast cancer, and
      hippocampal neuronal cells) and, finally, validated for visualization of dynamic
      living cells (hippocampal neurons).

PMID- 29328154
TI  - Effect of optical pumping on the dielectric properties of 0.6CaTiO3-0.4NdAlO3
      ceramics in the terahertz range.
AB  - The dielectric properties of 0.6CaTiO3-0.4NdAlO3 ceramics under external optical
      fields were investigated by terahertz time-domain spectroscopy in a frequency
      range of 0.2 THz to 1 THz at room temperature. It could be found that the
      variation of the real part of complex permittivity is approximately 0.31 in the
      frequency range of 0.2 THz to 1 THz. However the imaginary part of the dielectric
      constant does not change appreciably with the external optical field. The
      micromechanism of these results was attributed to the built-in electric field
      caused by the excited free carriers in the ceramics.

PMID- 29328155
TI  - Fast-switching optically isotropic liquid crystal nano-droplets with improved
      depolarization and Kerr effect by doping high k nanoparticles.
AB  - We proposed and analyzed an optically isotropic nano-droplet liquid crystal (LC)
      doped with high k nanoparticles (NPs), exhibiting enhanced Kerr effects, which
      could be operated with reduced driving voltages. For enhancing the contrast ratio
      together with the light efficiencies, the LC droplet sizes were adjusted to be
      shorter than the wavelength of visible light to reduce depolarization effects by
      optical scattering of the LC droplets. Based on the optical analysis of the
      depolarization effects, the influence of the relationship between the LC droplet
      size and the NP doping ratio on the Kerr effect change was investigated.

PMID- 29328156
TI  - Suppressing the influence of charge-coupled device vertical blooming on the
      measurement of laser beam quality factor (M2) of a near-infrared laser.
AB  - In this paper, a new method, which is based on reconstructing the original
      intensity distribution of a laser with images captured by a charge-coupled device
      (CCD) in two orthogonal directions, is proposed for suppressing the influence of
      CCD vertical blooming on the measurement of the laser beam quality factor (M2). A
      simplified theoretical model for the distribution of CCD blooming is also
      proposed. With the proposed method and model, the influence of CCD vertical
      blooming on the measurement of M2 is simulated. The experimental results
      demonstrate that the new method can be an effective means to measure the M2 of a
      near-infrared laser with a silicon CCD camera. The proposed method can be applied
      to a beam quality analyzer in order to suppress the influence of blooming on the
      measurement of M2.

PMID- 29328157
TI  - Talbot-Lau x-ray deflectometry phase-retrieval methods for electron density
      diagnostics in high-energy density experiments.
AB  - Talbot-Lau x-ray interferometry uses incoherent x-ray sources to measure
      refraction index changes in matter. These measurements can provide accurate
      electron density mapping through phase retrieval. An adaptation of the
      interferometer has been developed in order to meet the specific requirements of
      high-energy density experiments. This adaptation is known as a moire
      deflectometer, which allows for single-shot capabilities in the form of
      interferometric fringe patterns. The moire x-ray deflectometry technique requires
      a set of object and reference images in order to provide electron density maps,
      which can be costly in the high-energy density environment. In particular,
      synthetic reference phase images obtained ex situ through a phase-scan procedure,
      can provide a feasible solution. To test this procedure, an object phase map was
      retrieved from a single-shot moire image obtained from a plasma-produced x-ray
      source. A reference phase map was then obtained from phase-stepping measurements
      using a continuous x-ray tube source in a small laboratory setting. The two phase
      maps were used to retrieve an electron density map. A comparison of the moire and
      phase-stepping phase-retrieval methods was performed to evaluate single-exposure
      plasma electron density mapping for high-energy density and other transient
      plasma experiments. It was found that a combination of phase-retrieval methods
      can deliver accurate refraction angle mapping. Once x-ray backlighter quality is
      optimized, the ex situ method is expected to deliver electron density mapping
      with improved resolution. The steps necessary for improved diagnostic performance
      are discussed.

PMID- 29328158
TI  - Volume holographic spatial mode demultiplexer with a dual-wavelength method.
AB  - Volume holographic demultiplexers (VHDMs) provide spatial mode demultiplexing
      using simple optical systems. However, applying VHDM to practical optical
      communication systems is difficult, as typical holographic media have no
      sensitivity in the infrared region, which includes optical transmission bands. In
      this paper, we propose a VHDM scheme combined with a dual-wavelength method
      (DWM). Using the DWM, VHDMs are able to perform mode demultiplexing in the
      optical transmission bands. We experimentally demonstrated the basic operation of
      our proposal using experiments performed at an 850-nm wavelength. In addition, we
      performed numerical simulations to investigate the application of VHDM to the C
      band.

PMID- 29328159
TI  - Adaptive compensation of intracavity tilts during lasing through detecting the
      direction of output beams.
AB  - We present adaptive compensation of intracavity tilts based on detecting the
      direction of the output beams. We use the initial direction of the output beam
      when the laser cavity is well collimated for reference. Then the difference
      between the actual direction of the output beam and the reference is used as
      feedback to control the intracavity tip/tilt mirror. The relation between the
      direction of the output beam and the intracavity tilt is investigated with both
      the Fox-Li method and measurements. A series of experiments demonstrate that
      intracavity tilts can be well compensated by the proposed method. We have also
      proved that it is possible to substitute the proposed method for conventional
      extracavity beam stabilization.

PMID- 29328160
TI  - Frequency downconversion with independent multichannel phase shifting and zero
      intermediate-frequency receiving based on optical frequency shift and
      polarization multiplexing.
AB  - Photonic microwave frequency downconversion with independent multichannel phase
      shifting and zero-intermediate-frequency (IF) receiving via an integrated
      polarization multiplexing dual-parallel Mach-Zehnder modulator (MZM) is proposed.
      Based on the ideas of optical frequency shift and polarization multiplexing, the
      radio frequency (RF) signal is frequency downconverted to multichannel IF signals
      with the phases independently and arbitrarily tuned by adjusting the polarization
      controllers or even frequency downconverted to baseband directly by choosing two
      quadrature channels. In the simulation, the gain of our proposed frequency
      downconversion system is higher than that of the conventional two cascaded MZMs'
      system, and the phase shift with the range of 360 degrees  can be obtained
      concurrently. Furthermore, 2.5 Gbit/s RF vector signals centered at 10 GHz with
      different modulation formats are successfully demodulated.

PMID- 29328161
TI  - Ultrafast and low-power crystallization in Ge1Sb2Te4 and Ge1Sb4Te7 thin films
      using femtosecond laser pulses.
AB  - Rapid and reversible switching between amorphous and crystalline phases of phase
      change material promises to revolutionize the field of information processing
      with a wide range of applications including electronic, optoelectronics, and
      photonic memory devices. However, achieving faster crystallization is a key
      challenge. Here, we demonstrate femtosecond-driven transient inspection of
      ultrafast crystallization of as-deposited amorphous Ge1Sb2Te4 and Ge1Sb4Te7 thin
      films induced by a series of 120 fs laser pulses. The snapshots of phase
      transitions are correlated with the time-resolved measurements of change in the
      absorption of the samples. The crystallization is attributed to the reiterative
      excitation of an intermediate state with subcritical nuclei at a strikingly low
      fluence of 3.19  mJ/cm2 for Ge1Sb2Te4 and 1.59  mJ/cm2 for Ge1Sb4Te7.
      Furthermore, 100% volumetric crystallization of Ge1Sb4Te7 was achieved with the
      fluence of 4.78  mJ/cm2, and also reamorphization is seen for a continuous
      stimulation at the same repetition rate and fluence. A systematic confirmation of
      structural transformations of all samples is validated by Raman spectroscopic
      measurements on the spots produced by the various excitation fluences.

PMID- 29328162
TI  - Optical device terahertz integration in a two-dimensional-three-dimensional
      heterostructure.
AB  - The transmission properties of an off-planar integrated circuit including two
      wavelength division demultiplexers are designed, simulated, and analyzed in
      detail by the finite-difference time-domain method. The results show that the
      wavelength selection for different ports (0.404[c/a] at B2 port, 0.389[c/a] at B3
      port, and 0.394[c/a] at B4 port) can be realized by adjusting the parameters. It
      is especially important that the off-planar integration between two complex
      devices is also realized. These simulated results give valuable promotions in the
      all-optical integrated circuit, especially in compact integration.

PMID- 29328163
TI  - Bicontrollable terahertz metasurface with subwavelength scattering elements of
      two different materials.
AB  - Transmission of a normally incident plane wave through a metasurface with
      bicontrollable subwavelength scattering elements was simulated using a commercial
      software. Some pixels composing the H-shaped scattering elements were made of a
      magnetostatically controllable material whereas the remaining pixels were made of
      a thermally controllable material, the metasurface designed to operate in the
      terahertz spectral regime. The copolarized transmission coefficients were found
      to exhibit stopbands that shift when either a magnetostatic field is applied or
      the temperature is increased or both. Depending on spectral location of the
      stopband, either the magnetostatic field gives coarse control and temperature
      gives fine control or vice versa. The level of magnetostatic control depends on
      the magnetostatic-field configuration.

PMID- 29328164
TI  - Impact of input field characteristics on vibrational femtosecond coherent anti
      Stokes Raman scattering thermometry.
AB  - In this paper, three ultrashort-pulse coherent anti-Stokes Raman scattering
      (CARS) thermometry approaches are summarized with a theoretical time-domain
      model. The difference between the approaches can be attributed to variations in
      the input field characteristics of the time-domain model. That is, all three
      approaches of ultrashort-pulse (CARS) thermometry can be simulated with the
      unified model by only changing the input fields features. As a specific example,
      the hybrid femtosecond/picosecond CARS is assessed for its use in combustion flow
      diagnostics; thus, the examination of the input field has an impact on
      thermometry focuses on vibrational hybrid femtosecond/picosecond CARS. Beginning
      with the general model of ultrashort-pulse CARS, the spectra with different input
      field parameters are simulated. To analyze the temperature measurement error
      brought by the input field impacts, the spectra are fitted and compared to fits,
      with the model neglecting the influence introduced by the input fields. The
      results demonstrate that, however the input pulses are depicted, temperature
      errors still would be introduced during an experiment. With proper field
      characterization, however, the significance of the error can be reduced.

PMID- 29328165
TI  - Time-resolved study of optical properties and microscopic dynamics during the
      drying of TiO2 films by spectral diffusing wave spectroscopy.
AB  - We present a combined experimental, theoretical, and numerical study of photon
      transport and microscopic dynamics in rigid and drying turbid thin films. Our
      setup is based in multispeckle diffusing wave spectroscopy and is adapted for
      frequency sweep of the illuminating source. We apply our approach to
      simultaneously monitor the changes in optical properties and microscopic dynamics
      of turbid thin films of rutile TiO2 powder dispersed in ethanol during the full
      drying process. Accordingly, we introduce an extension of the photon diffusion
      model for spectral speckle intensity correlations to account for system
      microscopic dynamics. We find that our results are well described by the model,
      where parameters required as the time-dependent sample thickness and transport
      mean free path are obtained from experiments. Furthermore, our findings are
      validated by numerical simulations of speckle dynamics based on the copula
      scheme. We consider that our scheme could be useful in time-resolved physical
      characterization of time-evolving turbid thin systems.

PMID- 29328166
TI  - Comprehensive three-dimensional ray tracing model for three-mirror cavity
      enhanced spectroscopy.
AB  - A 3D ray tracing model is used to simulate optical reinjection in a nonresonant
      optical cavity, for off-axis integrated cavity output spectroscopy. The optical
      cavities are optimized for maximum intensity enhancement factors via a grid
      search and a genetic algorithm. Intensity enhancement factors up to 1400 are
      found for short cavities (3 cm) and up to 101 for long cavities (50 cm). The
      model predicts that short absorption cells can be used, having a long effective
      path length and a high throughput power. This opens new opportunities in the
      field of ultrasensitive absorption spectroscopy and allows the design of compact
      optical gas sensors.

PMID- 29328167
TI  - High-speed real-time heterodyne interferometry using software-defined radio.
AB  - This paper describes the design and performance of a phase demodulation scheme
      based on software-defined radio (SDR), applied in heterodyne interferometry. The
      phase retrieval is performed in real time by means of a low-cost SDR with a
      wideband optoelectronic front-end. Compared to other demodulation schemes, the
      system is quite simpler, versatile, and of lower cost. The performance of the
      demodulator is demonstrated by measuring the displacement per volt of a thin-film
      polymeric piezoelectric transducer based on polyvinylidene fluoride for
      ultrasonic applications. We measured displacements between 3.5 pm and 122 pm with
      7% relative uncertainty, in the frequency range from 20 kHz to 1 MHz.

PMID- 29328168
TI  - Simultaneous determination of the size and concentration of fine bubbles in water
      by laser-light scattering.
AB  - The preparation of nanoscale fine bubbles in water is an innovative technology,
      but no precise method for simultaneously measuring the size and concentration of
      such bubbles had previously been developed. We have developed a method for
      simultaneously determining the size and concentration of fine bubbles in water by
      a light-scattering technique. Dynamic light scattering gives the diffusion
      constant and particle size of fine bubbles, whereas static light scattering
      provides their concentration or molar mass. Static light scattering also provides
      the radius of gyration of the bubbles, thereby providing a means for validating
      measurements of the sizes of the fine bubbles.

PMID- 29328169
TI  - Inverse synthetic aperture LADAR demonstration: system structure, imaging
      processing, and experiment result.
AB  - A long-distance inverse synthetic aperture LADAR (ISAL) imaging experiment
      outdoors over 1 km for cooperative targets is demonstrated, which gets a two
      dimensional high-resolution image with resolution exceeding 2.5 cm. The system
      utilizes an electro-optic in-phase and quadrature modulator to output a linear
      frequency-modulated continuous waveform (LFMCW) with a bandwidth of 6 GHz and
      pulse repetition frequency (PRF) of 16.7 KHz. For the problem of the coherence of
      the laser, the effects of the coherent processing interval (CPI) and time delay
      of the local oscillator (LO) on the coherence are discussed. The fiber delay line
      is set and the CPI is reduced to lower the requirement of the frequency stability
      of the laser source. The images are formed by two-dimensional Fourier transform
      and joint time-frequency transform methods, respectively. In this paper, we
      present the system structure, imaging processing, and the experiment result in
      detail. The experiment result validates the performance of our system for ISAL
      imaging.

PMID- 29328170
TI  - Highly directive plasmonic structure with double resonance at excitation and
      emission for molecule-enhanced fluorescence.
AB  - An improved bull's eye nanostructure is proposed as a substrate for surface
      enhanced fluorescence. Optimized by finite-difference time-domain, annular
      corrugation on both upper and lower surfaces is placed around a nanobow tie in
      the middle. The whole structure is designed for the excitation and emission
      process of a certain fluorescence simultaneously, which can enhance the
      fluorescence intensity enormously (35 times for an excitation field and 120 times
      for radiation, independently). Meanwhile, it is able to confine the far-field
      emission energy within a divergence angle of +/-3.5 degrees . The dual-resonant
      enhancement and directivity of such a substrate allows higher sensitivity during
      fluorescence detection. Furthermore, the designed resonance and directional light
      control at emission may effectively reduce the required energy at excitation,
      which is ideal for those molecules with low laser damage threshold.

PMID- 29328171
TI  - Sequential fitting-and-separating reflectance components for analytical
      bidirectional reflectance distribution function estimation.
AB  - We present a sequential fitting-and-separating algorithm for surface reflectance
      components that separates individual dominant reflectance components and
      simultaneously estimates the corresponding bidirectional reflectance distribution
      function (BRDF) parameters from the separated reflectance values. We tackle the
      estimation of a Lafortune BRDF model, which combines a nonLambertian diffuse
      reflection and multiple specular reflectance components with a different specular
      lobe. Our proposed method infers the appropriate number of BRDF lobes and their
      parameters by separating and estimating each of the reflectance components using
      an interval analysis-based branch-and-bound method in conjunction with iterative
      K-ordered scale estimation. The focus of this paper is the estimation of the
      Lafortune BRDF model. Nevertheless, our proposed method can be applied to other
      analytical BRDF models such as the Cook-Torrance and Ward models. Experiments
      were carried out to validate the proposed method using isotropic materials from
      the Mitsubishi Electric Research Laboratories-Massachusetts Institute of
      Technology (MERL-MIT) BRDF database, and the results show that our method is
      superior to a conventional minimization algorithm.

PMID- 29328172
TI  - Simultaneous trilateral communication based on three mutually coupled chaotic
      semiconductor lasers with optical feedback.
AB  - In this paper, we propose a chaos-based scheme allowing for trilateral
      communication among three mutually coupled chaotic semiconductor lasers. The
      coupling through a partially transparent optical mirror between two lasers
      induces the chaotic dynamics. We numerically solve the delay rate equations of
      three lasers and demonstrate that the dynamics is completely synchronous. Herein,
      each laser is not only a transmitter but a receiver; three different messages are
      encoded by simultaneously modulating bias current of the three lasers. By
      monitoring the synchronization error between transmitter and receiver, and
      comparing the error with the message of the local laser, we can decipher the
      message of the sender. The investigation indicates that these messages introduced
      on the two ends of each link among three lasers can be simultaneously transmitted
      and restored, so the system can realize simultaneous trilateral communication. In
      this scheme, an eavesdropper can monitor the synchronization error, but one has
      no way to obtain the bits that are being sent, so the trilateral communication is
      secure.

PMID- 29328173
TI  - Random fiber laser based on artificially controlled backscattering fibers.
AB  - The random fiber laser (RFL), which is a milestone in laser physics and nonlinear
      optics, has attracted considerable attention recently. Most previously reported
      RFLs are based on distributed feedback of Rayleigh scattering amplified through
      the stimulated Raman-Brillouin scattering effect in single-mode fibers, which
      require long-distance (tens of kilometers) single-mode fibers and high threshold,
      up to watt level, due to the extremely small Rayleigh scattering coefficient of
      the fiber. We proposed and demonstrated a half-open-cavity RFL based on a segment
      of an artificially controlled backscattering single-mode fiber with a length of
      210 m, 310 m, or 390 m. A fiber Bragg grating with a central wavelength of 1530
      nm and a segment of artificially controlled backscattering single-mode fiber
      fabricated by using a femtosecond laser form the half-open cavity. The proposed
      RFL achieves thresholds of 25 mW, 30 mW, and 30 mW, respectively. Random lasing
      at a wavelength of 1530 nm and extinction ratio of 50 dB is achieved when a
      segment of 5 m erbium-doped fiber is pumped by a 980 nm laser diode in the RFL. A
      novel RFL with many short cavities has been achieved with low threshold.

PMID- 29328174
TI  - Mapping geometry in Fizeau transmission spheres with a small f-number.
AB  - The ideal mapping geometry in a Fizeau interferometer is to map equal height
      increments on a flat object and equal angle increments on a spherical surface to
      equal heights on the detector. So the initial intent of the optical design of
      Fizeau transmission spheres (TSs) is to provide R-theta mapping geometry for
      equal angle increments. The corresponding unequal heights mapping will introduce
      retrace error as coma when linear carrier fringes exist. On the contrary, equal
      heights mapping with R-sin theta mapping geometry will avoid linear carrier
      fringes induced coma error. These two different mapping geometries conflict
      especially for the TS with a small f-number. In this paper, we will first explore
      the design and the performance of the f/0.75  TS according to the two different
      mapping geometries, and then evaluate the mapping geometry for the commercial
      ZYGO f/0.75  TS, and give some engineering notes for the designers, the
      metrologists, and the fabricators in the optical laboratory.

PMID- 29328175
TI  - Dependence of the birefringence of polystyrene film on the stretching conditions.
AB  - We investigated the dependence of the birefringence of polystyrene (PS) film with
      a negative optical birefringence on the stretching conditions. We varied the
      stretching ratio (SR), stretching speed (SS), and stretching temperature (ST),
      and measured the inplane birefringence and the Nz coefficient of the PS film. The
      inplane birefringence was increased with greater SR and SS but decreased with
      greater ST. The Nz coefficient of the stretched PS film was around zero and
      showed similar dependence on the stretching conditions like inplane
      birefringence.

PMID- 29328176
TI  - Ultra-sensitive quasi-distributed temperature sensor based on an apodized fiber
      Bragg grating.
AB  - This work targets a remarkable quasi-distributed temperature sensor based on an
      apodized fiber Bragg grating. To achieve this, the mathematical formula for a
      proposed apodization function is carried out and tested. Then, an optimization
      parametric process required to achieve the remarkable accuracy that is based on
      coupled mode theory (CMT) is done. A detailed investigation for the side lobe
      analysis, which is a primary judgment factor, especially in quasi-distributed
      configuration, is investigated. A comparison between elite selection of
      apodization profiles (extracted from related literatures) and the proposed
      modified-Nuttal profile is carried out covering reflectivity peak, full width
      half maximum (FWHM), and side lobe analysis. The optimization process concludes
      that the proposed modified-Nuttal profile with a length (L) of 15 mm and
      refractive index modulation amplitude (Deltan) of 1.4*10-4 is the optimum choice
      for single-stage and quasi-distributed temperature sensor networks. At previous
      values, the proposed profile achieves an acceptable reflectivity peak of 10-0.426
      dB, acceptable FWHM of 0.0808 nm, lowest side lobe maximum (SL max) of 7.037*10
      12  dB, lowest side lobe average (SL avg) of 3.883*10-12  dB, and lowest side
      lobe suppression ratio (SLSR) of 1.875*10-11  dB. These optimized characteristics
      lead to an accurate single-stage sensor with a temperature sensitivity of 0.0136
      nm/ degrees C. For the quasi-distributed scenario, a noteworthy total isolation
      of 91 dB is achieved without temperature, and an isolation of 4.83 dB is achieved
      while applying temperature of 110 degrees C for a five-stage temperature-sensing
      network. Further investigation is made proving that consistency in choosing the
      apodization profile in the quasi-distributed network is mandatory. If the
      consistency condition is violated, the proposed profile still survives with a
      casualty of side lobe level rise of -73.2070  dB when adding uniform apodization
      and -46.4823  dB when adding Gaussian apodization to the five-stage modified
      Nuttall temperature-sensing network.

PMID- 29328177
TI  - Projected image correction technology research on autonomous-perception
      anisotropic surfaces.
AB  - In this paper, a projection correction method is proposed for autonomous
      perception depth anisotropic surfaces, in order to improve the adaptive
      perceptual projection of the projection equipment under different circumstances.
      During the parameter calibration process of a projector-camera system with low
      recognition precision, as well as low noise resistance at angular points, an
      angular-point subpixel detection algorithm based on color information guidance
      was proposed to effectively improve the identification precision of the angular
      point detection. Meanwhile, the projection geometry correction algorithm was
      proposed, which was based on the topology analysis, in order to analyze the
      spatial topology distribution of the depth anisotropic surface and also to solve
      the homography matrix in the different regions of the anisotropic surface.
      Eventually, the homography matrix was used for the geometric distortion
      correction of the projection distortion image. The experimental analysis showed
      that the identification accuracy of the proposed method achieved 0.25 pixels,
      with simultaneous high planar parallelism and liner perpendicularity. Through
      utilizing the method proposed by us for the projection correction of the depth
      anisotropic surface, it was confirmed that the geometric distortion correction
      precision of the proposed method had reached the subpixel level, and the
      consistency level of the imaging picture was also confirmed.

PMID- 29328178
TI  - Determination of toxic and essential metals in rock and sea salts using pulsed
      nanosecond laser-induced breakdown spectroscopy.
AB  - A spectrometer based on pulsed nanosecond laser-induced breakdown spectroscopy
      (LIBS) was employed for the quantitative determination of heavy and essential
      metals in salts from various sources available in Pakistan. Six salt samples were
      collected from sea salt and rock salt. Toxic metals (Cu, Cd, and Ni) and other
      microessentials (Fe, Ca, Co, Mg, Mn, S, and Zn) were investigated from the
      recorded spectra. The detection system was calibrated using a parametric
      dependence study. The quantitative analyses were accomplished under the
      assumption of local thermodynamic equilibrium and optically thin plasma. The
      results by the LIBS technique were in agreement with the outcomes of the same
      samples studied using a more standard approach like inductively coupled plasma
      atomic emission spectroscopy (ICP-AES). When the concentrations of heavy and
      essential metals were calculated using a calibration-free LIBS method that does
      not need a standard salt specimen and dilution, both LIBS and ICP-AES were also
      in good agreement. The limit of detection of the experimental set up was
      determined for the observed heavy metals in the studied samples.

PMID- 29328179
TI  - Beam shape coefficient calculation for a Gaussian beam: localized approximation,
      quadrature and angular spectrum decomposition methods.
AB  - Three methods for calculating the beam shape coefficients (the quadrature, the
      angular spectrum decomposition (ASD), and the localized approximation methods)
      are studied. The normalized associated Legendre function is employed in the
      calculation so as to prevent overflow. The two-dimensional integrations in the
      quadrature and the ASD methods are developed to the one-dimensional integration
      to speed up the calculation. The Gaussian beams reconstructed with different
      methods are compared, showing the difference in the remodeling effects of these
      methods. The reason for the presence of pseudodistribution in the localized model
      is given.

PMID- 29328180
TI  - Modulation transfer function of a fish-eye lens based on the sixth-order wave
      aberration theory.
AB  - A calculation program of the modulation transfer function (MTF) of a fish-eye
      lens is developed with the autocorrelation method, in which the sixth-order wave
      aberration theory of ultra-wide-angle optical systems is used to simulate the
      wave aberration distribution at the exit pupil of the optical systems. The
      autocorrelation integral is processed with the Gauss-Legendre integral, and the
      magnification chromatic aberration is discussed to calculate polychromatic MTF.
      The MTF calculation results of a given example are then compared with those
      previously obtained based on the fourth-order wave aberration theory of plane
      symmetrical optical systems and with those from the Zemax program. The study
      shows that MTF based on the sixth-order wave aberration theory has satisfactory
      calculation accuracy even for a fish-eye lens with a large acceptance aperture.
      And the impacts of different types of aberrations on the MTF of a fish-eye lens
      are analyzed. Finally, we apply the self-adaptive and normalized real-coded
      genetic algorithm and the MTF developed in the paper to optimize the Nikon F/2.8
      fish-eye lens; consequently, the optimized system shows better MTF performances
      than those of the original design.

PMID- 29328181
TI  - Super-resolution image de-fencing using a nonlocal nonconvex prior.
AB  - Today's smartphones/phablets/tablets are equipped with cameras that have enabled
      people to capture their favorite moments. However, images or videos taken at
      public places using inexpensive low-resolution cameras are often degraded by the
      presence of occlusions such as fences/barricades. In order to reconstruct a fence
      free high-resolution image, we use a video of a scene captured by panning a hand
      held camera and model the effects of various degradations. Initially, we obtain
      the spatial locations of fences by semantic segmentation and subsequently
      estimate the subpixel motion between the degraded low-resolution frames. The
      unknown high-resolution de-fenced image is modeled as a nonlocal discontinuity
      adaptive Markov random field (NL-DAMRF) and its maximum a posteriori estimate is
      obtained by minimizing an appropriate objective function. We propose a nonlocal
      extension of DAMRF prior to preserve high-frequency information in the
      reconstruction process. Specifically, we use the graduated nonconvexity algorithm
      to minimize the proposed nonconvex energy function. Experiments with both
      synthetic and real-world data demonstrate the efficacy of the proposed algorithm.

PMID- 29328182
TI  - Mechano-optical modulator based on a rotating optical flat applied to
      simultaneous holographic multiplexing of gratings.
AB  - Simultaneous holographic multiplexing methods are used to store multiple
      holograms concurrently into one holographic volume. Compared to serial exposure,
      one advantage is the higher processing speed. Additionally, for parallel exposure
      the different gratings develop in a linear relation to one another, although the
      developing process itself is nonlinear caused by the holographic photopolymer. A
      mechano-optical modulator using a rotating optical flat is introduced to enable
      economic single-shot exposure of centimeter to decimeter-sized holograms
      utilizing only one laser. The modulator specifically suppresses undesired
      interference, which occurs with this type of simultaneous exposure. A device
      concept of the modulator is presented. The application to simultaneous
      holographic multiplexing is theoretically discussed and experimentally
      demonstrated. The experimental results are compared to simulations and are
      evaluated. The functionality and practicability are proven, giving rise to a new
      design concept and a wider range of applications.

PMID- 29328183
TI  - Ultrafast multipulse damage threshold of femtosecond high reflectors.
AB  - Laser-induced damage threshold is a fundamental figure of merit of femtosecond
      optical components used in large-scale laser systems. We tested a series of
      ultrafast mirrors featuring high band-gap dielectric materials as well as
      improved design and coating techniques. In a broad range of the damage test pulse
      train involving between 10 and 100,000 pulses (40 fs, 800 nm), pure dielectric
      high reflectors exhibit around 1.5  J/cm2 and hybrid Ag-multilayer mirrors can
      exhibit well above 1.2  J/cm2 damage threshold. In addition, a reference
      antireflection coating exceeded 2  J/cm2. Damage threshold dependence on the
      number of pulses was similar for all optics involved.

PMID- 29328184
TI  - Extinction spectra of suspensions of microspheres: determination of the spectral
      refractive index and particle size distribution with nanometer accuracy.
AB  - A method is presented to infer simultaneously the wavelength-dependent real
      refractive index (RI) of the material of microspheres and their size distribution
      from extinction measurements of particle suspensions. To derive the averaged
      spectral optical extinction cross section of the microspheres from such ensemble
      measurements, we determined the particle concentration by flow cytometry to an
      accuracy of typically 2% and adjusted the particle concentration to ensure that
      perturbations due to multiple scattering are negligible. For analysis of the
      extinction spectra, we employ Mie theory, a series-expansion representation of
      the refractive index and nonlinear numerical optimization. In contrast to other
      approaches, our method offers the advantage to simultaneously determine size,
      size distribution, and spectral refractive index of ensembles of microparticles
      including uncertainty estimation.

PMID- 29328185
TI  - Optical fiber humidity sensor based on the direct response of the polyimide film.
AB  - An optical fiber humidity sensor based on an optical Fabry-Perot interferometer
      is proposed and experimentally demonstrated. The sensor is constructed by a short
      section of hollow-core fiber coated with a polyimide (PI) film. Taking advantage
      of the direct response of the PI film, a sensitivity of up to 1.309 nm/%RH can be
      achieved in the humidity change range from 40% RH to 80% RH. The temperature
      sensitivity is measured to be 43.57 pm/ degrees C when the temperature changes
      from 25 degrees C to 55 degrees C. Because of its simple structure, fast response
      time, convenient production, and good reproducibility, the proposed sensor will
      be competitive in the field of cultural relic humidity monitoring and
      pharmaceutical storage.

PMID- 29328186
TI  - Single crystal Er3+ : YAG fibers with tailored refractive index profiles.
AB  - Erbium-doped yttrium aluminum garnet (Er3+:YAG) rods were inserted inside undoped
      tubes and grown into single-crystal fibers of a diameter of 300 MUm using the
      laser-heated pedestal growth technique. Growth at various rates resulted in
      radially graded distributions of Er3+ dopant ions, as observed using laser
      induced fluorescence imaging. Profiles of the refractive index were measured
      using cross-sectional reflectometry in a microscope. Dopant distributions and the
      corresponding index profiles were compared with thermal diffusion theory to
      determine the inter-diffusion coefficient of Y3+ and Er3+ ions at 2000 degrees C,
      yielding an estimated value of D=(9.10+/-0.8)*10-11  m2/s. This work constitutes
      a step toward controlled growth of fibers with high thermal conductivities, low
      Brillouin gain, and waveguiding properties required for high-power optical
      amplifier and laser applications.

PMID- 29328187
TI  - Kilohertz binary phase modulator for pulsed laser sources using a digital
      micromirror device.
AB  - The controlled modulation of an optical wavefront is required for aberration
      correction, digital phase conjugation, or patterned photostimulation. For most of
      these applications, it is desirable to control the wavefront modulation at the
      highest rates possible. The digital micromirror device (DMD) presents a cost
      effective solution to achieve high-speed modulation and often exceeds the speed
      of the more conventional liquid crystal spatial light modulator but is inherently
      an amplitude modulator. Furthermore, spatial dispersion caused by DMD diffraction
      complicates its use with pulsed laser sources, such as those used in nonlinear
      microscopy. Here we introduce a DMD-based optical design that overcomes these
      limitations and achieves dispersion-free high-speed binary phase modulation. We
      show that this phase modulation can be used to switch through binary phase
      patterns at the rate of 20 kHz in two-photon excitation fluorescence
      applications.

PMID- 29328188
TI  - Plasmon mediated inverse Faraday effect in a graphene-dielectric-metal structure.
AB  - This Letter shows the features of inverse Faraday effect (IFE) in a graphene
      dielectric-metal (GDM) structure. The constants of propagation and attenuation of
      the surface plasmon-polariton modes are calculated. The effective magnetic field
      induced by surface plasmon modes in the dielectric due to the IFE is estimated to
      reach above 1 tesla. The possibility to control the distribution of the magnetic
      field by chemical potential of graphene is shown. The concept of strain-driven
      control of the IFE in the structure has been proposed and investigated.

PMID- 29328189
TI  - Massive ordering and alignment of cylindrical micro-objects by photovoltaic
      optoelectronic tweezers.
AB  - Optical tools for manipulation and trapping of micro- and nano-objects are a
      fundamental issue for many applications in nano- and biotechnology. This work
      reports on the use of one such method, known as photovoltaic optoelectronics
      tweezers, to orientate and organize cylindrical microcrystals, specifically
      elongated zeolite L, on the surface of Fe-doped LiNbO3 crystal plates. Patterns
      of aligned zeolites have been achieved through the forces and torques generated
      by the bulk photovoltaic effect. The alignment patterns with zeolites parallel or
      perpendicular to the substrate surface are highly dependent on the features of
      light distribution and crystal configuration. Moreover, dielectrophoretic chains
      of zeolites with lengths up to 100 MUm have often been observed. The experimental
      results of zeolite trapping and alignment have been discussed and compared
      together with theoretical simulations of the evanescent photovoltaic electric
      field and the dielectrophoretic potential. They demonstrate the remarkable
      capabilities of the optoelectronic photovoltaic method to orientate and pattern
      anisotropic microcrystals. The combined action of patterning and alignment offers
      a unique tool to prepare functional nanostructures with potential applications in
      a variety of fields such as nonlinear optics or plasmonics.

PMID- 29328190
TI  - Orbital angular momentum generation via a spiral phase microsphere.
AB  - Vortex beam carrying orbital angular momentum (OAM) attracts much attention in
      many research fields for its special phase and intensity distributions. In this
      Letter, a novel design called the spiral phase microsphere (SPMS) is proposed for
      the first time, to the best of our knowledge, which can convert incident plane
      wave light into the focused vortex beam that carries OAM with different
      topological charges l=+/-1 and +/-2. The vortex beam generation is verified by a
      self-interfered modification of the SPMS. The generation of the vortex beams by
      the SPMS irradiated by a single-wavelength incident light is studied using the
      CST MICROWAVE STUDIO simulation. The SPMS provides a new approach to achieve high
      efficiency and high-integrated photonic applications related with OAM.

PMID- 29328191
TI  - Dispersion-managed Ho-doped fiber laser mode-locked with a graphene saturable
      absorber.
AB  - In this Letter, we demonstrate an all-fiber holmium-doped laser operating in the
      stretched-pulse regime. As a result of dispersion management, the laser is
      capable of generating 190 fs pulses with a bandwidth of 53.6 nm. The pulses
      centered at 2060 nm reach 2.55 nJ of energy. Mode-locking is achieved with a
      multilayer graphene saturable absorber (SA). The Letter also presents the
      measurement of group velocity dispersion of active (Nufern SM-HDF-10/130),
      passive (SMF28), and dispersion-compensating (Nufern UHNA4) fibers in a 1.8-2.1
      MUm range. To the best of our knowledge, this is the first report on an all
      fiber, stretched-pulse laser operating beyond 2 MUm with nanomaterial-based SA.

PMID- 29328192
TI  - Near quantum-noise limited and absolute frequency stabilized 1083  nm single
      frequency fiber laser.
AB  - The Earth's magnetic field has significant effects that protect us from cosmic
      radiation and provide navigation for biological migration. However, slow temporal
      variations originating in the liquid outer core invariably exist. To understand
      the working mechanism of the geomagnetic field and improve accuracy of navigation
      systems, a high-precision magnetometer is essential to measure the absolute
      magnetic field. A helium optically pumping magnetometer is an advanced approach,
      but its sensitivity and accuracy are directly limited by the low-frequency
      relative intensity noise and frequency stability characteristics of a light
      source. Here, we demonstrate a near quantum-noise limited and absolute frequency
      stabilized 1083 nm single-frequency fiber laser. The relative intensity noise is
      only 5 dB higher than the quantum-noise limit, and the root mean square of
      frequency fluctuation is ~17  kHz after locked. This fiber laser could suppress
      the fluctuation of magnetic resonant frequency and improve the signal-to-noise
      ratio of the magnetic resonance signal detection.

PMID- 29328193
TI  - Polarization-insensitive and wide-incident-angle optical absorber with
      periodically patterned graphene-dielectric arrays.
AB  - A polarization-insensitive and angle-independent graphene absorber (GA) with
      periodically patterned grating is demonstrated. A periodic nanocavity composed of
      multilayer subwavelength grating and metal substrate supports a strongly
      localized mode inside the cavity, where the mode helps to absorb more
      electromagnetic waves. The proposed GA exhibits polarization-insensitive behavior
      and maintains the high absorption above 90% within a wide range of incident angle
      (more than 80 degrees ). We attribute the high absorption to the excitation of
      the cavity mode resonance and magnetic resonance for the transverse electric and
      transverse magnetic polarizations, respectively. The proposed GA has potential
      applications in the design of various devices, such as optical modulators or
      tunable absorption filters because of its remarkable angle-insensitive absorption
      performance.

PMID- 29328194
TI  - Subwavelength wave manipulation in a thin surface-wave bandgap crystal.
AB  - It has been recently reported that the unit cell of wire media metamaterials can
      be tailored locally to shape the flow of electromagnetic waves at deep
      subwavelength scales [Nat. Phys.9, 55 (2013)NPAHAX1745-247310.1038/nphys2480].
      However, such bulk structures have a thickness of at least the order of
      wavelength, thus hindering their applications in the on-chip compact plasmonic
      integrated circuits. Here, based upon a Sievenpiper "mushroom" array [IEEE Trans.
      Microwave Theory Tech.47, 2059 (1999)IETMAB0018-948010.1109/22.798001], which is
      compatible with standard printed circuit board technology, we propose and
      experimentally demonstrate the subwavelength manipulation of surface waves on a
      thin surface-wave bandgap crystal with a thickness much smaller than the
      wavelength (1/30th of the operating wavelength). Functional devices including a T
      shaped splitter and sharp bend are constructed with good performance.

PMID- 29328195
TI  - Geometrical optimization of nanostrips for surface plasmon excitation: an
      analytical approach.
AB  - We give a simple tool for the optimization of the dimensions of a metallic
      nanostrip illuminated at a given wavelength under normal incidence, to get a
      maximum of the electromagnetic field amplitude in the nanostrip. We propose an
      analytical formula that gives the widths and heights of the series of nanostrips
      that produce field enhancement. The validity of the analytical formula is checked
      by using the finite element method. This design of a nanostrip could be useful
      for sensors and thermally active components.

PMID- 29328196
TI  - Anisotropy of nonlinear optical absorption of LBO crystals at 355  nm.
AB  - The dependence of the nonlinear optical absorption coefficients on the intensity
      and polarization of pulsed laser radiation at 355 nm was investigated for lithium
      triborate (LBO) crystals using the piezoelectric resonance laser calorimetry.

PMID- 29328197
TI  - Fiber Bragg grating fabricated in micro-single-crystal sapphire fiber.
AB  - This Letter introduces a fiber Bragg grating (FBG) in a micro-single-crystal
      sapphire fiber (micro-SFBG) for sensing applications in high-temperature and
      harsh environments. The FBG was fabricated by a point-by-point method via an IR
      femtosecond laser in a large-diameter sapphire fiber that was then wet-hot acid
      etched to achieve microfiber size, which culminated in fabricating and
      characterizing a 9.6 MUm diameter micro-SFBG. The refractive index measurement
      ranging from 1 to 1.75 and temperature measurement from room temperature to 1400
      degrees C are also reported.

PMID- 29328198
TI  - Stable vortex soliton in nonlocal media with orientational nonlinearity.
AB  - We report on the first experimental observation of stable vortex solitons in
      nematic liquid crystals with nonlocal nonlinear reorientational response. We show
      how these nonlinear vortex beams can be formed and confined in extraordinary
      optical waves by employing the cell with no lateral boundary conditions and the
      application of an external magnetic field that effectively controls the molecular
      direction and propagation of the self-trapped beams. We also find that these
      vortex solitons can be generated in certain ranges of the input beam power.

PMID- 29328199
TI  - Silicon-on-insulator microring resonator sensor based on an amplitude comparison
      sensing function.
AB  - A novel, highly sensitive integrated sensor based on a silicon-on-insulator
      microring resonator is proposed and experimentally demonstrated. To achieve a
      fast-response and cost-effective sensing system, the new structure establishes a
      linear amplitude comparison sensing function (ACSF) by monitoring the optical
      powers from both the through port and drop port of an add-drop microring
      resonator simultaneously, where the contrast of the two ports eliminates the
      effect of unexpected power fluctuation of the input laser on sensor performance.
      A highly enhanced linear relationship between the resonant wavelength shift and
      the ACSF value is achieved with an R-squared value over 0.99. A proof-of-concept
      experiment for temperature sensing demonstrates an almost constant ACSF with only
      +/-0.9% discrepancy, while the laser power is varied between 0 dBm and -7  dBm.

PMID- 29328200
TI  - Super pulses of orbital angular momentum in fractional-order spiroid vortex
      beams.
AB  - We consider optical properties of hypergeometric-Gaussian beam compositions with
      spiral-like intensity and phase distributions called spiroid beams. Their orbital
      angular momentum as a function of a fractional-order topological charge has a
      chain of super-pulses (bursts and dips). The form of the super-pulses can be
      controlled by the spiral parameters. Such a phenomenon can be used in optical
      switches and triggers for optical devices and communication systems.

PMID- 29328201
TI  - Selective generation of Lamb modes by a moving continuous-wave laser.
AB  - This Letter focuses on the selectively non-contact generation of Lamb wave modes
      in plates by using a continuous-wave (CW) laser moving along sample surface.
      Compared with the generated Lamb waves with broadband, multiple modes (the
      existence of at least two modes at any given frequency) excited by a pulsed
      laser, the desired single narrowband mode of the Lamb wave can be generated by a
      moving CW laser, as long as the scanning speed matches the phase velocity of the
      mode. Moreover, the dispersion curves of the Lamb wave can be obtained directly
      from the power spectrum of the time-domain signal recorded at each laser's moving
      speed. Single A0 mode excitation, coupled resonance phenomenon of A0 mode and S0
      mode, single S0 mode excitation, and high-order modes appeared successively as
      scanning speed increased. Especially, the excitation of the pure single S0 mode
      can be realized, which is suitable for propagation in the case of liquid loading.
      It is proposed, for the first time to the best of our knowledge, to realize the
      selection of a single Lamb wave mode by using the CW laser scanning method, which
      provides a brand-new way for laser ultrasonic excitation.

PMID- 29328202
TI  - Inclined emitting slotted single-mode laser with 1.7 degrees  vertical divergence
      angle for PIC applications.
AB  - In this Letter, a new type of single-mode slotted laser used for an on-chip light
      source in photonic integrated circuits is proposed. An inclined light beam with a
      low vertical divergence angle can be directly coupled into the surface grating of
      the silicon to form an integrated light source. Experimentally, a III-V laser
      with a 54.6 degrees  inclined angle and a vertical divergence angle of 1.7
      degrees  is achieved by introducing a kind of specially distributed
      microstructure. The side mode suppression ratio is better than 45 dB, and the
      continuous wave output power reaches 6.5 mW at room temperature. We report the
      inclined emitting microstructured single-mode laser with a low divergence angle
      for the first time, to the best of our knowledge.

PMID- 29328203
TI  - Polarization control of terahertz radiation from two-color femtosecond gas
      breakdown plasma.
AB  - We individually control polarizations of 800 and 400 nm beams, which form a two
      color femtosecond plasma filament in air irradiating a linear-to-elliptical THz
      signal. We detected a threshold-like appearance of THz ellipticity at the angle
      of ~85 degrees  between the fundamental and second-harmonic field polarization
      directions. The simulations confirm the abrupt change of THz polarization and
      reveal that the weak ellipticity of the second harmonic is sufficient to generate
      essentially elliptical THz radiation.

PMID- 29328204
TI  - Broadband nonvolatile photonic switching based on optical phase change materials:
      beyond the classical figure-of-merit.
AB  - In this Letter, we propose a broadband, nonvolatile on-chip switch design in the
      telecommunication C-band with record low loss and crosstalk. The unprecedented
      device performance builds on: 1) a new optical phase change material (O-PCM)
      Ge2Sb2Se4Te1 (GSST), which exhibits significantly reduced optical attenuation
      compared to traditional O-PCMs, and 2) a nonperturbative design that enables low
      loss device operation beyond the classical figure-of-merit (FOM) limit. We
      further demonstrate that the 1-by-2 and 2-by-2 switches can serve as basic
      building blocks to construct nonblocking and nonvolatile on-chip switching fabric
      supporting arbitrary numbers of input and output ports.

PMID- 29328205
TI  - Flexible pulse-stretching for a swept source at 2.0  MUm using free-space angular
      chirp-enhanced delay.
AB  - Dispersive pulse-stretching at 2.0 MUm has long been hindered by the high
      intrinsic optical loss from conventional dispersive media. Here a flexible pulse
      stretching technique at 2.0 MUm is demonstrated over a broad bandwidth with large
      scale dispersion and low intrinsic optical loss. The technique employs the newly
      proposed pulse-stretching scheme, namely, free-space angular-chirp-enhanced
      delay. Both normal and anomalous temporal dispersion (up to +/-500  ps/nm) with
      low intrinsic loss (<6  dB) over a spectral bandwidth of ~84  nm at 2.0 MUm is
      obtained with low nonlinear effects. Based on this method, an optical wavelength
      swept source at 2.0 MUm is realized and applied to spectrally encoded imaging at
      a line scan rate of ~19  MHz, proving the potential of this pulse-stretching
      technique for continuous single-shot measurements at the 2.0 MUm wavelength
      regime, particularly for optical microscopy and spectroscopy.

PMID- 29328206
TI  - Fabrication of helical photonic structures with submicrometer axial and spatial
      periodicities following "inverted umbrella" geometry through phase-controlled
      interference lithography.
AB  - In this Letter we report for the first time, to the best of our knowledge, a
      phase spatial light modulator (SLM)-based interference lithography (IL) approach
      for the realization of hexagonally packed helical photonic structures with a
      submicrometer scale spatial, as well as axial, periodicity over a large area. A
      phase-only SLM is used to electronically generate six phase-controlled plane
      beams. These six beams from the front side and a direct central backside beam are
      used together in an "inverted umbrella" geometry setup to realize the desired
      submicrometer axial periodic chiral photonic structures through IL. The realized
      structures with 650 nm spatial and 353 nm axial periodicities on negative
      photoresist can be used as an optical filter and refractive index sensor, as
      evidenced from the FDTD-based simulation study on its optical properties.
      Further, the fabricated templates can be transferred to metals such as silver or
      aluminum for the realization of a metamaterial-based broadband circular polarizer
      ranging from 1 to 3.5 MUm of near-infrared spectra.

PMID- 29328207
TI  - 13  dB squeezed vacuum states at 1550  nm from 12  mW external pump power at 775 
      nm.
AB  - Strongly squeezed light at telecommunication wavelengths is a necessary resource
      for one-sided device-independent quantum key distribution via fiber networks.
      Reducing the optical pump power that is required for its generation will advance
      this quantum technology towards efficient out-of-laboratory operation. Here, we
      investigate the second-harmonic pump power requirement for parametric generation
      of continuous-wave squeezed vacuum states at 1550 nm in a state-of-the-art doubly
      resonant standing-wave periodically poled potassium titanyl phosphate cavity
      setup. We use coarse adjustment of the Gouy phase via the cavity length, together
      with temperature fine-tuning, for simultaneously achieving double resonance and
      (quasi) phase matching, and observe a squeeze factor of 13 dB at 1550 nm from
      just 12 mW of external pump power at 775 nm. We anticipate that optimizing the
      cavity coupler reflectivity will reduce the external pump power to 3 mW, without
      reducing the squeeze factor.

PMID- 29328208
TI  - Absorption of laser plasma in competition with oscillation currents for a
      terahertz spectrum.
AB  - We generate terahertz radiation in a supersonic jet of nitrogen molecules pumped
      by intense two-color laser pulses. The tuning of terahertz spectra from blue
      shift to red shift is observed by increasing laser power and stagnation pressure,
      and the red shift range is enlarged with the increased stagnation pressure. Our
      simulation reveals that the plasma absorption of the oscillation currents and
      expanded plasma column owing to increased laser intensity and gas number density
      are crucial factors in the recurrence of the red shift of terahertz spectra. The
      findings disclose the microscopic mechanism of terahertz radiation and present a
      controlling knob for the manipulation of a broadband terahertz spectrum from
      laser plasma.

PMID- 29328209
TI  - Observation of spatial optical diametric drive acceleration in photonic lattices.
AB  - We experimentally and theoretically demonstrate a spatial diametric drive
      acceleration of two mutually incoherent optical beams in 1D optical lattices
      under a self-defocusing nonlinearity. The two beams, exciting the modes at the
      top/bottom edges of the first Bloch band and hence experiencing normal/anomalous
      diffraction, can bind together and bend in the same direction during nonlinear
      propagation, analogous to the interplay between two objects with opposite signs
      of mass that breaks Newton's third law. Their spatial spectrum changes associated
      with the acceleration are analyzed for different lattice modulations. We find
      that the acceleration limit is determined by the beam exciting the top band edge
      that reaches a saturated momentum change prior to the other pairing beam.

PMID- 29328210
TI  - Nonlinear absorption and temperature-dependent fluorescence of perovskite FAPbBr3
      nanocrystal.
AB  - Recent progress in solar cell and light-emitting devices makes halide perovskite
      a research hot spot in optics. In this Letter, the nonlinear absorption and
      fluorescence properties of FAPbBr3 nanocrystal, one typical organometallic halide
      perovskite, have been investigated via Z-scan measurements and a density
      dependent photoluminescence (PL) spectrum. The FAPbBr3 nanocrystal exhibits
      nonlinear absorption under the excitation of 800 nm, whose photon energy is below
      the bandgap of FAPbBr3. The significant absorption is experimentally confirmed to
      be induced by two-photon absorption (TPA), and the TPA coefficient is measured to
      be ~0.0042  cm/GW. Moreover, the PL induced by TPA in FAPbBr3 nanocrystal shows
      different temperature-dependent behaviors in the range of 90 to 350 K. The peaks
      of the PL spectrum remain nearly constant at 100-160  K, with a very shallow
      trough at around 150 K, while a linear blue shift (0.496 meV/K) of the spectrum
      is observed when temperature is above 160 K. These temperature-dependent
      fluorescence behaviors can be ascribed to the structural phase transition at
      about 150 K and the contribution of thermal expansion. Moreover, the exciton
      binding energy around 160 meV and the optical phonon energy of 15.3 meV are also
      extracted from the temperature-dependent PL data.

PMID- 29328211
TI  - Effects of defocus on the transfer function of coherence scanning interferometry.
AB  - Coherence scanning interferometry (CSI) offers three-dimensional (3D) measurement
      of surface topography with high precision and accuracy. Defocus within the
      interferometric objective lens, however, is commonly present in CSI measurements
      and reduces both the resolving power of the imaging system and the ability to
      measure tilted surfaces. This Letter extends the linear theory of CSI to consider
      the effects of defocus on the 3D transfer function and the point spread function
      in an otherwise ideal CSI instrument. The results are compared with measurements
      of these functions in a real instrument. This work provides further evidence for
      the validity of the linear systems theory of CSI.

PMID- 29328212
TI  - High-throughput microchannel fabrication in fused silica by temporally shaped
      femtosecond laser Bessel-beam-assisted chemical etching.
AB  - We proposed combining temporally shaped (double-pulse train) laser pulses with
      spatially shaped (Bessel beam) laser pulses. By using a temporally shaped
      femtosecond laser Bessel-beam-assisted chemical etching method, the energy
      deposition efficiency was improved by adjusting the pulse delay to yield a
      stronger material modification and, thus, a higher etching depth. The etching
      depth was enhanced by a factor of 13 using the temporally shaped Bessel beam. The
      mechanism of etching depth enhancement was elucidated by localized transient-free
      electrons dynamics-induced structural and morphological changes. Micro-Raman
      spectroscopy was conducted to verify the structural changes inside the material.
      This method enables high-throughput, high-aspect-ratio microchannel fabrication
      in fused silica for potential applications in microfluidics.

PMID- 29328213
TI  - Iodine-stabilized single-frequency green InGaN diode laser.
AB  - A 520-nm InGaN diode laser can emit a milliwatt-level, single-frequency laser
      beam when the applied current slightly exceeds the lasing threshold. The laser
      frequency was less sensitive to diode temperature and could be finely tuned by
      adjusting the applied current. Laser frequency was stabilized onto a hyperfine
      component in an iodine transition through the saturated absorption spectroscopy.
      The uncertainty of frequency stabilization was approximately 8*10-9 at a 10-s
      integration time. This compact laser system can replace the conventional green
      diode-pumped solid-state laser and applied as a frequency reference. A single
      longitudinal mode operational region with diode temperature, current, and output
      power was investigated.

PMID- 29328214
TI  - Efficient, 2-5  MUm tunable CdSiP2 optical parametric oscillator pumped by a
      laser source at 1.57  MUm.
AB  - We report on first demonstrations of CdSiP2-based optical parametric oscillators
      that are pumped by eye-safe Q-switched nanosecond laser sources operating at 1.57
      MUm. One device reached 40% optical conversion efficiency generating 10 mJ of
      energy near degeneracy in the 3 MUm region. Angle tuning of a similar device
      through the middle infrared was demonstrated with the signal and idler waves
      being tuned from 2.28 MUm to 5.05 MUm.

PMID- 29328215
TI  - Cascaded four-wave mixing in the XUV region.
AB  - We present a detailed study of the wave-mixing process in the extreme ultraviolet
      (XUV) region (around 30 nm) by using two collinear multiple-cycle laser pulses
      with incommensurate frequencies (wavelengths 1400 and 800 nm). The experimental
      data provide evidence for the coherent accumulation of wave-mixing fields and a
      high third-order response of the medium in this spectral range. We show that the
      time evolution of the mixing fields can be used to study the coherence dynamics
      of the free-electron wave packet with a lifetime of 200-750 fs.

PMID- 29328216
TI  - Photoacoustic and hyperspectral dual-modality endoscope.
AB  - We have developed a dual-modality endoscope composed of photoacoustic (PA) and
      hyperspectral imaging, capable of visualizing both structural and functional
      properties of bio-tissue. The endoscope's composition and scanning mechanism was
      described, and the feasibility of the dual-modality endoscope was verified by
      mimic phantom experiments. Lately, we demonstrated its endoscopic workability
      through in vivo experiments. The experimental results showed that the proposed
      herein hybrid endoscope can provide optical imaging of the surface and tomography
      imaging for the deeper features, and a functional oxygen saturation rate map of
      the same imaging area. We demonstrated optical-resolution PA imaging of vascular
      structures and an oxygen saturation rate map in a rabbit's rectum. It confirmed
      that this dual-modality endoscope can play an important role in comprehensive
      clinical applications.

PMID- 29328217
TI  - Differential loss magnetic field sensor using a ferrofluid encapsulated D-shaped
      optical fiber.
AB  - A ferrofluid immersed, D-shape optical fiber exhibits differential loss up to 12
      dB with respect to an azimuthally rotating magnetic field placed around its
      longitudinal axis, manifested in its measured transmission power. Investigating
      the magneto induced refractive index and loss changes by using ferrofluid
      overlaid diffractive elements a differential loss mechanism is revealed,
      associated with the relative light polarization direction and the magnetic field
      application direction. The results were used for performing modal profile
      simulations of ferrofluid immersed D-shape optical fiber. It is demonstrated that
      such an optical system can act as a magnetic field sensor with field angle and
      intensity sensing capabilities.

PMID- 29328218
TI  - Scattering cross-sectional modulation in photoacoustic remote sensing microscopy.
AB  - Modeling and observations of large scattering cross-sectional modulations in
      absorbing optical scatterers due to a pulsed laser excitation are reported. Rapid
      laser-induced thermo-elastic expansion produces nontrivial perturbations to the
      local refractive indices. This mechanism forms the basis of a recent non-contact
      photoacoustic technique known as photoacoustic remote sensing microscopy. A time
      evolution model is constructed and discussed, comparing it with existing planar
      models, time-independent models, and experiments. Fractional scattering cross
      sectional modulations greater than 20 times that of the unperturbed particles are
      predicted and observed for the first time, to the best of our knowledge. A
      nonlinear acoustic enlargement effect is likewise predicted and observed.
      Implications of system and material properties are explored.

PMID- 29328219
TI  - Quantum limits on the time-bandwidth product of an optical resonator.
AB  - A thought-provoking proposal by Tsakmakidis et al. [Science356, 1260
      (2017)SCIEAS0036-807510.1126/science.aam6662] suggests that nonreciprocal optics
      can break a time-bandwidth limit to passive resonators. Here I quantize their
      resonator model and show that quantum mechanics does impose a limit, or requires
      extra noise to be added in the same fashion as amplified spontaneous emission in
      an active resonator. I also use thermodynamics to argue that extra dissipation or
      noise must be present in their proposed device.

PMID- 29328220
TI  - Fabrication of optical vortex lattices based on holographic polymer-dispersed
      liquid crystal films.
AB  - This Letter demonstrates optical vortex lattices based on holographic polymer
      dispersed liquid crystal (HPDLC) films. The fabrication method uses a phase-only
      reflective spatial light modulator with numerically calculated phase profiles
      loaded on it to simplify multi-helical-wave interference. The beam profiles of
      the diffraction beams are simulated using the Fourier transform and compared with
      experimental results. The topological charges of the 1st-order diffraction beams
      reconstructed from the HPDLC films are examined using a Michelson interferometer.

PMID- 29328221
TI  - Localized excitation of polarized light emission by cathodoluminescence
      spectroscopy.
AB  - Surface plasmons (SPs), the resonance of free electrons on the metal-air
      interface, may strongly interact with light and generate some extraordinary
      optical effects. Instead of using conventional planar light excitation, here we
      excite SPs with a focused electron beam on metallic nanostructures with different
      geometrical symmetries. With the help of a polarizer and filter in the detection
      system, we obtain cathodoluminescence (CL) images with different polarizations at
      certain wavelengths. The maxima in the CL images show that the focused electron
      beam may efficiently excite luminescence with different polarizations at
      different spots. Comparing the data collected on the structures with specific
      geometrical symmetry, we demonstrate that the polarization of the emitted light
      depends on both the structural symmetry and the excitation location. We suggest
      that this Letter is enlightening to understand the relationship between the SP
      resonance on the structure and the emission of CL with different polarizations.

PMID- 29328222
TI  - Doppler-free Fourier transform spectroscopy.
AB  - Sub-Doppler broadband multi-heterodyne spectroscopy is proposed and
      experimentally demonstrated. Using two laser frequency combs of slightly
      different repetition frequencies, we have recorded Doppler-free two-photon dual
      comb spectra of atomic rubidium resonances of a width of 6 MHz, while
      simultaneously interrogating a spectral span of 10 THz. The atomic transitions
      are uniquely identified via the intensity modulation of the observed fluorescence
      radiation. To the best of our knowledge, these results represent the first
      demonstration of Doppler-free Fourier transform spectroscopy and extend the range
      of applications of broadband spectroscopy towards precision nonlinear
      spectroscopy.

PMID- 29328223
TI  - Self-referenced octave-wide subharmonic GaP optical parametric oscillator
      centered at 3  MUm and pumped by an Er-fiber laser: erratum.
AB  - This erratum reports a correction to the labeling of Figs. 2(b) and 3(b) in the
      original manuscript, Opt. Lett.42, 4756 (2017)OPLEDP0146
      959210.1364/OL.42.004756.

PMID- 29328224
TI  - Magnetometry using fluorescence of sodium vapor.
AB  - Magnetic resonance of sodium fluorescence is studied with varying laser
      intensity, duty cycle, and field strength. A magnetometer based on a sodium vapor
      cell filled with He buffer gas is demonstrated, using a single amplitude
      modulated laser beam. With a 589 nm laser tuned at the D1 or D2 line, the
      magnetic field is inferred from the variation of fluorescence. A magnetic field
      sensitivity of 150  pT/Hz is achieved at the D1 line. The work is an important
      step toward sensitive remote magnetometry with mesospheric sodium.

PMID- 29328225
TI  - Transversely coupled Fabry-Perot resonators with Bragg grating reflectors.
AB  - We design and demonstrate Fabry-Perot resonators with transverse coupling using
      Bragg gratings as reflectors on the silicon-on-insulator (SOI) platform. The
      effects of tailoring the cavity length and the coupling coefficient of the
      directional coupler on the spectral characteristics of the device are studied.
      The fabricated resonators achieved an extinction ratio (ER) of 37.28 dB and a Q
      factor of 3356 with an effective cavity length of 110 MUm, and an ER of 8.69 dB
      and a Q-factor of 23642 with a 943 MUm effective cavity length. The resonator
      structure presented here has the highest reported ER on SOI and provides
      additional degrees of freedom compared to an all-pass ring resonator to tune the
      spectral characteristics.

PMID- 29328226
TI  - Intensity modulation of a terahertz bandpass filter: utilizing image currents
      induced on MEMS reconfigurable metamaterials.
AB  - We experimentally demonstrated a tunable terahertz bandpass filter based on
      microelectromechanical systems (MEMS) reconfigurable metamaterials. The unit cell
      of the filter consists of two split-ring resonators (SRRs) and a movable bar.
      Initially, the movable bar situates at the center of the unit cell, and the
      filter has two passbands whose central frequencies locate at 0.65 and 0.96 THz.
      The intensity of the two passbands can be actively modulated by the movable bar,
      and a maximum modulation depth of 96% is achieved at 0.96 THz. The mechanism of
      tunability is investigated using the finite-integration time-domain method. The
      result shows that the image currents induced on the movable bar are opposite the
      resonance currents induced on the SRRs and, thus, weaken the oscillating
      intensity of the resonance currents. This scheme paves the way to dynamically
      control and switch the terahertz wave at some constant frequencies utilizing
      induced image currents.

PMID- 29328227
TI  - Wide-angle transmissions of electromagnetic fields through the sandwiched
      transparent epsilon-near-zero metamaterial screen.
AB  - We propose a sandwiched transparent epsilon-near-zero (ENZ) metamaterial screen
      to release the obliquely incident electromagnetic fields. More specifically, the
      transmission properties through ENZ metamaterials are investigated when
      incorporated with an interlayer of a meta-surface having periodic complementary
      spiral-resonator-matrixes. We show that both TE- and TM-polarized electromagnetic
      waves are capable of penetrating the ENZ metamaterials under a wide-angle range
      of illuminations, and the greatly enhanced transmissions are turning out to be
      frequency dispersionless for different polarized electromagnetic fields with
      different incident angles. Our design, breaking the notion of the angular filter
      of ENZ metamaterials, should readily be applied to other extreme-parameter
      materials and pave the way to explore more unexpected transmission properties of
      these metamaterials.

PMID- 29328228
TI  - Quadrature squeezing of a higher-order sideband spectrum in cavity optomechanics.
AB  - We propose an efficient scheme to generate quadrature squeezing of a higher-order
      sideband spectrum in an optomechanical system. This is achieved by exploiting a
      well-established optomechanical circumstance, where a second-order nonlinearity
      is embedded into the optomechanical cavity driven by a strong control field and a
      weak probe pulse. Using experimentally achievable parameters, we demonstrate that
      the second-order nonlinearity intensity and the frequency detuning of a control
      field allow us to modify the amplitude of higher-order sidebands and improve the
      amount of squeezing of a higher-order sideband spectrum. Furthermore, in the
      presence of a strong second-order nonlinearity, an optimizing quadrature
      squeezing of a higher-order sideband spectrum can be achieved, which provides a
      practical opportunity to design the squeezed frequency combs and other precision
      measurements.

PMID- 29328229
TI  - Two-mode surface plasmon lasing in hexagonal arrays.
AB  - We demonstrate surface-plasmon lasing in hexagonal metal hole arrays with a
      semiconductor gain medium. The device can be tuned between two laser modes, with
      distinct wavelengths, spatial distributions, and polarization patterns, by
      changing the size of the optically pumped area. One of the modes exhibits a six
      fold polarization pattern, while the mode observed for larger pump spots has a
      rotationally symmetric polarization pattern. We explain the mode tuning by the
      differences of in-plane and radiative out-of-plane losses of the modes. The
      spatial and polarization properties of the modes are conveniently described by a
      sum of vectorial orbital angular momentum beams with orbital, spin, and total
      angular momentum j=l+s.

PMID- 29328230
TI  - High-efficiency 2  MUm Tm:YAP laser with a compact mechanical Q-switch.
AB  - We describe a compact, highly efficient, diode-pumped, mechanically Q-switched
      Tm:YAP laser operating near 2 MUm. The Q-switch, based on a torsion spring
      resonant mirror scanner, had negligible optical loss and required very low
      electrical drive power. At a 10 kHz pulse repetition frequency, the laser
      generated an average output power of 10.5 W at 1.94 MUm, Q-switched pulse energy
      of 1.05 mJ, a pulse length of 31 ns, and a peak power of 34 kW. The Q-switched
      laser exhibited maximum optical and electrical efficiencies of 51% and 26%,
      respectively.

PMID- 29328231
TI  - Aberration-accounting calibration for 3D single-molecule localization microscopy.
AB  - We propose a straightforward sample-based technique to calibrate the axial
      detection in 3D single-molecule localization microscopy. Using microspheres
      coated with fluorescent molecules, the calibration curves of point spread
      function-shaping or intensity-based measurements can be obtained over the imaging
      depth range. This experimental method takes into account the effect of the
      spherical aberration without requiring computational correction. We demonstrate
      its efficiency for astigmatic imaging in a 1.2 MUm range above the coverslip.

PMID- 29328232
TI  - CEP dependence of signal and idler upon pump-seed synchronization in optical
      parametric amplifiers.
AB  - We study the effect of pump-seed timing fluctuations on the carrier-envelope
      phase (CEP) of signal and idler pulses emerging from an OP(CP)A. A simple
      analytical model is derived in order to provide an intuitive explanation of the
      origin of CEP fluctuations, while split-step simulations are performed to cover a
      broad range of different seeding schemes. Finally, we compare the simulation
      results with real observations of the CEP of idler pulses generated by an OPA.
      The quantitative model presented provides a key tool for designing the next
      generation of low-noise CEP-stable OP(CP)A-based sources.

PMID- 29328233
TI  - Nonlinearity-aware 200  Gbit/s DMT transmission for C-band short-reach optical
      interconnects with a single packaged electro-absorption modulated laser.
AB  - We experimentally demonstrate the transmission of a 200 Gbit/s discrete multitone
      (DMT) at the soft forward error correction limit in an intensity-modulation
      direct-detection system with a single C-band packaged distributed feedback laser
      and traveling-wave electro absorption modulator (DFB-TWEAM), digital-to-analog
      converter and photodiode. The bit-power loaded DMT signal is transmitted over 1.6
      km standard single-mode fiber with a net rate of 166.7 Gbit/s, achieving an
      effective electrical spectrum efficiency of 4.93 bit/s/Hz. Meanwhile, net rates
      of 174.2 Gbit/s and 179.5 Gbit/s are also demonstrated over 0.8 km SSMF and in an
      optical back-to-back case, respectively. The feature of the packaged DFB-TWEAM is
      presented. The nonlinearity-aware digital signal processing algorithm for channel
      equalization is mathematically described, which improves the signal-to-noise
      ratio up to 3.5 dB.

PMID- 29328234
TI  - Relative sensitivity variation law in the field of fluorescence intensity ratio
      thermometry.
AB  - We study the variation law of relative sensitivity in the field of fluorescence
      intensity ratio thermometry. It is theoretically demonstrated that there must be
      only one maximum value of relative sensitivity in the case in which there is a
      positive offset in fitting function. Moreover, the method to obtain this maximum
      is proposed. Experimental results, taking the D15/D50 levels of Eu3+ as examples,
      are in excellent accordance with the conclusion. The mechanism behind is then
      investigated, and other populating processes imposed on the D15 level, which
      exert negative outcome on thermal sensitivity, are found to play a key role in
      determination of this unique variation law.

PMID- 29328235
TI  - Non-diffracting beams for label-free imaging through turbid media.
AB  - We propose a new method to image through dynamically changing turbid media based
      on the scanning of non-diffractive laser beams. We use computer-generated
      holograms to create Airy beams and compare quantitatively the characteristics of
      their propagation in clear and turbid media. Imaging contrast is achieved by
      relative reflection of the scanned beams from the imaged surface. We implement
      our method to demonstrate experimentally our ability to image a chromium surface
      on a glass slide through 270 MUm of highly scattering milk/water mixtures with a
      resolution of several microns.

PMID- 29328236
TI  - Real-time Fourier transformation based on the bandwidth magnification of RF
      signals.
AB  - We demonstrate a novel real-time Fourier transformation scheme with megahertz
      level resolution realized by bandwidth magnification of radio frequency (RF)
      signals. Before the frequency-to-time mapping, the RF signal is modulated on an
      optical frequency comb, and then extracted by a Vernier comb filter. As a result,
      RF components can be separated in the spectrum with a greatly magnified optical
      bandwidth. Thus, even with limited dispersion provided by an ordinary optical
      fiber, the frequency-dependent pulses can be distinguished in the time domain.
      Experimentally, the RF signal with the frequency difference of 60 MHz is
      separated by around 123 ps in the time domain, equivalent to the dispersion of
      1975.5 ps/GHz (2.47*105  ps/nm), while the physical dispersion is 1500 ps/nm.
      Thus, based on the bandwidth magnification of signals, the dispersion is
      equivalently amplified by 165 times.

PMID- 29328238
TI  - 2  MUm Doppler wind lidar with a Tm:fiber-laser-pumped Ho:YLF laser.
AB  - A 2 MUm Ho-doped ytrrium lithium fluoride (Ho:YLF) laser end-pumped by a 1.94 MUm
      Tm:fiber laser was developed. A laser system of a ring resonator oscillator and
      amplifier was operated at repetition rates of 200-5000 Hz at room temperature.
      The Q-switched outputs were 7.4 W at 5000 Hz and 4.25 W at 200 Hz. Injection
      seeding was applied to the ring resonator, and single-mode laser emission was
      obtained. The Tm:fiber-laser-pumped Ho:YLF laser was first used for Doppler wind
      lidar measurements, and wind profiles were obtained up to ranges of about 15 km
      in a range resolution of 96 m and an integration time of 1 s.

PMID- 29328237
TI  - Visible light optical coherence microscopy of the brain with isotropic femtoliter
      resolution in vivo.
AB  - Most flying-spot optical coherence tomography and optical coherence microscopy
      (OCM) systems use a symmetric confocal geometry, where the detection path
      retraces the illumination path starting from and ending with the spatial mode of
      a single-mode optical fiber. Here we describe a visible light OCM instrument that
      breaks this symmetry to improve transverse resolution without sacrificing
      collection efficiency in scattering tissue. This was achieved by overfilling a
      water immersion objective on the illumination path while maintaining a
      conventional Gaussian mode detection path (1/e2 intensity diameter ~0.82 Airy
      disks), enabling ~1.1  MUm full width at half-maximum (FWHM) transverse
      resolution. At the same time, a ~0.9  MUm FWHM axial resolution in tissue,
      achieved by a broadband visible light source, enabled femtoliter volume
      resolution. We characterized this instrument according to paraxial coherent
      microscopy theory and, finally, used it to image the meningeal layers,
      intravascular red blood cell-free layer, and myelinated axons in the mouse
      neocortex in vivo through the thinned skull.

PMID- 29328239
TI  - TE-polarized design for metallic slit lenses: a way to deep-subwavelength
      focusing over a broad wavelength range.
AB  - Slit arrays based on noble metals have been widely proposed as planar transverse
      magnetic (TM)-lenses, illuminated by a linearly polarized light with the
      polarization perpendicular to slits and implementing the focusing capability
      beyond the diffraction limit. However, due to intrinsic plasmonic losses, these
      TM-lenses cannot work efficiently in the ultraviolet wavelengths. In this Letter,
      taking advantage of the unique transmission through metallic slits not involving
      plasmonic losses, a metallic slit array with transverse-electric (TE)-polarized
      design is proposed, showing for the first time, to the best of our knowledge, the
      realization of sub-diffraction-limit focusing for ultraviolet light.
      Additionally, in contrast to the situations of TM-lenses, a wider slit leads to a
      greater phase delay and much larger slits can be arranged to construct the TE
      lenses, which is quite beneficial for practical fabrication. Furthermore, deep
      subwavelength focusing can be achieved by utilizing the immersing technology.

PMID- 29328240
TI  - Comparison of optical feedback dynamics of InAs/GaAs quantum-dot lasers emitting
      solely on ground or excited states.
AB  - We experimentally compare the dynamics of InAs/GaAs quantum dot lasers under
      optical feedback emitting exclusively on ground states (GSs) or excited states
      (ESs). By varying the feedback parameters and putting focus either on their short
      or long cavity regions, various periodic and chaotic oscillatory states are
      found. The GS laser is shown to be more resistant to feedback, benefiting from
      its strong relaxation oscillation damping. In contrast, the ES laser can easily
      be driven into complex dynamics. While the GS laser is of importance for the
      development of isolator-free transmitters, the ES laser is essential for
      applications taking advantages of chaos.

PMID- 29328241
TI  - Single-shot Fourier ptychography based on diffractive beam splitting.
AB  - An optical setup and corresponding reconstruction algorithm are proposed to
      realize single-shot Fourier ptychography (FP). Multiple angle-varied object waves
      are generated by placing a Dammann grating at a certain distance behind the
      object, and the generated image array of low resolution corresponding to
      different diffraction orders formed on the detector plane is recorded
      simultaneously in a single exposure. The amplitude, as well as the phase
      information of the object, can be properly reconstructed with a common FP
      algorithm from the recorded image array. This method eliminates the requirement
      for the angular scanning of common FP, and the total acquisition time is
      dramatically reduced. The feasibility of this proposed method was demonstrated
      both numerically and experimentally. The proposed method has the advantages of
      fast data acquisition and corresponding high temporal resolution, making it very
      suitable for applications in which high imaging speed is required.

PMID- 29328242
TI  - Efficient diode-pumped Er:KLu(WO4)2 laser at ~1.61  MUm.
AB  - We report on an efficient diode-pumped continuous-wave erbium-doped monoclinic
      double tungstate laser. It is based on a 1 at. % Er3+:KLu(WO4)2 (Er:KLuW) crystal
      cut along the Ng optical indicatrix axis. The Er:KLuW microchip laser, diode
      pumped at 0.98 MUm, generates 268 mW at 1.610 MUm with a slope efficiency of 30%.
      The output is linearly polarized (E||Nm), and the laser beam is nearly
      diffraction limited (Mp,m2<1.1). Spectroscopic properties of Er3+ in KLuW are
      also presented. The stimulated-emission cross-section sigmaSE is 0.46*10-20  cm2
      at ~1.609  MUm for E||Nm. The microchip Er:KLuW laser outperforms the commercial
      Er,Yb:glass.

PMID- 29328243
TI  - Spatiotemporal sharply autofocused dual-Airy-ring Airy Gaussian vortex wave
      packets.
AB  - Here we investigate the propagation properties of spatiotemporal sharply
      autofocused single-Airy-ring Airy Gaussian vortex (AiRAiGV) and dual-Airy-ring
      Airy Gaussian vortex (dAiRAiGV) wave packets by solving the (3+1) D Schrodinger
      equation in free space. We can change the spatial part of the wave packets into
      Airy or Gaussian distribution by choosing the different spatial distribution
      factors bs. In particular, only when the shape of the pulses is set well with
      appropriate temporal distribution factor bt and initial velocity v in the
      temporal domain, dAiRAiGV wave packets can simultaneously autofocus in the
      spatial and temporal domains and the peak intensity is increased dozens of times
      at the focus more than that at the initial plane. Furthermore, properties of
      dAiRAiGV wave packets with a vortex in the center and off-axis vortex pairs are
      also discussed.

PMID- 29328244
TI  - Equivalence principle and quantum mechanics: quantum simulation with entangled
      photons.
AB  - Einstein's equivalence principle (EP) states the complete physical equivalence of
      a gravitational field and corresponding inertial field in an accelerated
      reference frame. However, to what extent the EP remains valid in non-relativistic
      quantum mechanics is a controversial issue. To avoid violation of the EP,
      Bargmann's superselection rule forbids a coherent superposition of states with
      different masses. Here we suggest a quantum simulation of non-relativistic
      Schrodinger particle dynamics in non-inertial reference frames, which is based on
      the propagation of polarization-entangled photon pairs in curved and birefringent
      optical waveguides and Hong-Ou-Mandel quantum interference measurement. The
      photonic simulator can emulate superposition of mass states, which would lead to
      violation of the EP.

PMID- 29328245
TI  - Raman dissipative soliton fiber laser pumped by an ASE source: publisher's note.
AB  - This publisher's note corrects a typo in the affiliations in Opt. Lett.42, 5162
      (2017)OPLEDP0146-959210.1364/OL.42.005162.

PMID- 29328246
TI  - Plasmon-enhanced luminescence in novel complex conjugated polymer nanoparticles:
      publisher's note.
AB  - This publisher's note corrects errors in the affiliations in Opt. Lett.42, 3789
      (2017).OPLEDP0146-959210.1364/OL.42.003789.

PMID- 29328247
TI  - Femtosecond Alexandrite laser passively mode-locked by an InP/InGaP quantum-dot
      saturable absorber.
AB  - An Alexandrite laser passively mode-locked using an InP/InGaP quantum-dot
      semiconductor saturable absorber mirror (QD-SESAM) was demonstrated. The laser
      was pumped at 532 nm and generated pulses as short as 380 fs at 775 nm with an
      average output power of 295 mW. To the best of our knowledge, this is the first
      report on a passively mode-locked femtosecond Alexandrite laser using a SESAM in
      general and a QD-SESAM in particular.

PMID- 29328248
TI  - Filamentation-free self-compression of mid-infrared pulses in birefringent
      crystals with second-order cascading-enhanced self-focusing nonlinearity.
AB  - We experimentally demonstrate virtually lossless, filamentation-free and energy
      scalable more than three-fold self-compression of mid-infrared laser pulses at
      2.1 MUm in a birefringent medium (beta-BBO crystal), which stems from favorable
      interplay between the second-order cascading-enhanced self-phase modulation and
      anomalous group velocity dispersion. By choosing an appropriate input beam
      diameter and intensity, the self-compression down to sub-30 fs pulse widths with
      gigawatt peak power is achieved without the onset of beam filamentation and
      associated nonlinear losses due to the multiphoton absorption, yielding the
      energy throughput greater than 86%.

PMID- 29328249
TI  - Broadband near-infrared antireflection coatings fabricated by three-dimensional
      direct laser writing.
AB  - Three-dimensional direct laser writing via two-photon polymerization is used to
      fabricate anti-reflective structured surfaces (ARSSs) composed of subwavelength
      conicoid features optimized to operate over a wide bandwidth in the near-infrared
      range from 3700  cm-1 to 6600  cm-1 (2.7-1.52 MUm). Analytic Bruggemann effective
      medium calculations are used to predict nominal geometric parameters such as the
      fill factor of the constitutive conicoid features of the anti-reflective
      structured surfaces (ARSSs) presented here. The performance of the ARSSs was
      investigated experimentally using infrared reflection and transmission
      measurements. An enhancement of the transmittance by 1.35%-2.14% over a broadband
      spectral range from 3700  cm-1 to 6600  cm-1 (2.7-1.52 MUm) was achieved. We
      further report on finite-element-based reflection and transmission data using
      three-dimensional (3D) model geometries for comparison. A good agreement between
      experimental results and the finite-element-based numerical analysis is observed
      once as-fabricated deviations from the nominal conicoid forms are included in the
      model. 3D direct laser writing is demonstrated here as an efficient method for
      the fabrication and optimization of ARSSs designed for the infrared spectral
      range.

PMID- 29328250
TI  - Ultrafast saturable absorption of MoS2 nanosheets under different pulse-width
      excitation conditions.
AB  - The newly raised two-dimensional material MoS2 is regarded as an ideal candidate
      for saturated absorbers. Here, the open-aperture Z-scan method is used to study
      the saturation absorption (SA) response of monolayer and multilayer MoS2,
      considering laser irradiation with different pulse widths. Specifically, in cases
      of 10 ns and 10 ps laser pulses, the accumulative nonlinearity [e.g., free
      carrier absorption (FCA)] coupled with SA is found in both monolayer and
      multilayer MoS2. However, under a 65 fs pulse laser, the instantaneous
      nonlinearity [e.g., two-photon absorption (TPA)] and the SA effect turn to play a
      significant role. Additionally, the saturation of both TPA and FCA is observed in
      MoS2. Importantly, the modulation depth of MoS2 shows different change trends by
      adjusting the laser pulse width.

PMID- 29328251
TI  - Cavity-birefringence-dependent h-shaped pulse generation in a thulium-holmium
      doped fiber laser.
AB  - We report on a type of 2 MUm h-shaped pulse generation in a thulium-holmium-doped
      fiber laser and experimentally investigate its cavity birefringence and pump
      power dependences. An asymmetric nonlinear optical loop mirror is employed as an
      artificial saturable absorber, which incorporates ~52.7  m dispersion-shifted
      fiber and ~3.8  m ultra-high numerical aperture fiber to enhance the
      nonlinearity. The h-shaped pulse shows both a polarization state (PS) and pump
      power related evolutions, even when randomly weak birefringence fibers are
      employed. By further incorporating different lengths of high birefringence
      polarization-maintaining fiber (PMF), i.e., introducing different amounts of
      linear cavity birefringence, much larger pulse tuning ranges can be realized. In
      particular, when the PMF is lengthened to ~2.3  m through manipulating the PS,
      the achieved longest pulse duration of ~318.14  ns can almost cover the whole
      repetition period of ~323.96  ns, corresponding to a pulse duty circle of ~98.2%,
      the largest ever reported from a fiber laser, to the best of our knowledge. We
      demonstrate the related characteristics in detail.

PMID- 29328252
TI  - Phase modulator mode based on the pre-transitional effect of antiferroelectric
      liquid crystals.
AB  - We demonstrate a novel phase-only modulation mode based on the pre-transitional
      effect of the antiferroelectric liquid crystal. 2pi phase modulation without
      changing the polarization state of the incident light is achieved with a low
      field (1.8 V/MUm). This phase modulation mode also shows an ultrafast response
      time (less than 300 MUs) and a uniform optical texture with an easy fabrication
      process. This phase modulator can be applied to laser beam steering, virtual
      reality, and holograms, etc., in the future.

PMID- 29328253
TI  - Measurements of milli-Newton surface tension forces with tilted fiber Bragg
      gratings.
AB  - Small lateral forces (lower than 0.1 N) cannot normally be measured with
      conventional single-mode fiber-based sensors because of the high value of their
      Young modulus (>70  GPa). Here we demonstrate the measurement of lateral forces
      in the range from 0.2 to 1.4*10-3  N with a tilted fiber Bragg grating (TFBG) in
      conventional single-mode fiber pushed against the surface tension (ST) of a bead
      of water. The measured transmission changes of individual cladding mode
      resonances of the TFBG corresponding to these force values are of the order of 29
      dB. Separate measurements of the contact angle between the surface of the water
      and the fiber are used to calibrate the sensor with help from the known value of
      ST for water. Once calibrated, a TFBG can be used to measure unknown forces in
      the same range or to measure an unknown ST, provided a separate force measurement
      is available.

PMID- 29328254
TI  - Optically induced transparency in bosonic cascade lasers.
AB  - Bosonic cascade lasers are terahertz (THz) lasers based on stimulated radiative
      transitions between bosonic condensates of excitons or exciton-polaritons
      confined in a trap. We study the interaction of an incoming THz pulse resonant in
      frequency with the transitions between neighboring energy levels of the cascade.
      We show that at certain optical pump conditions the cascade becomes transparent
      to the incident pulse: it neither absorbs nor amplifies it in the mean-field
      approximation. The populations of intermediate levels of the bosonic cascade
      change as the THz pulse passes, nevertheless. In comparison, a fermionic cascade
      laser does not reveal any of these properties.

PMID- 29328255
TI  - Continuous-wave-induced resonant spectral sidebands in soliton fiber lasers.
AB  - We observed the resonant sidebands similar to the Kelly sidebands, but caused by
      the coupling between continuous-wave (CW) and dispersive waves (DWs) in a mode
      locked ring fiber laser for the first time, to the best of our knowledge. The
      coupling between the CW and DWs is a linear process, which is different from the
      previously observed parametric sub-sidebands. The regimes of the CW-induced
      sidebands are discussed. The experimental results agree both qualitatively and
      quantitatively with theoretical analysis. The results enrich the nonlinear
      dynamics of ultrafast fiber lasers and may have potential in optically
      controlling mode-locked lasers.

PMID- 29328256
TI  - Nanoscale beam splitters based on gradient metasurfaces.
AB  - Beam splitters are essential components in various optical and photonic
      applications, for example, interferometers, multiplexers, and so on. Present beam
      splitters based on cubes or plates are normally bulky. Realizing beam splitters
      in nanoscales is useful to reduce the total size of photonic devices. We
      demonstrate here a beam splitter with nanoscale thickness based on a gradient
      metasurface comprising lithium niobate cylinder arrays. Since one unit cell of
      metasurface comprising two cylinder rows shows two opposite phase gradients, the
      incident light is split into different directions according to the generalized
      Snell's law. The split ratio is proven to be effectively tunable.

PMID- 29328257
TI  - Multi-electrode tunable liquid crystal lenses with one lithography step.
AB  - Electrically tunable lenses offer the possibility to control the focal distance
      by applying an electric field. Different liquid crystal tunable lenses have been
      demonstrated. In order to minimize lens aberrations, multi-electrode designs
      allow us to fine-tune the applied voltages for every possible focal distance. In
      this Letter, we provide a novel multi-electrode design in which only one
      lithography step is necessary, thereby offering a greatly simplified fabrication
      procedure compared to earlier proposed designs. The key factor is the use of a
      high-permittivity layer, in combination with floating electrodes.

PMID- 29328258
TI  - Quantum anomalous Hall-quantum spin Hall effect in optical superlattices.
AB  - We consider the topological characteristics of the spin-orbital coupling
      particles loaded in one-dimensional (1D) optical superlattices subject to the
      Zeeman field. The phase shift of the superlattice provides a virtual dimension
      which allows us to simulate two-dimensional topological phases with a physically
      1D system. The system possesses a variety of quantum phase transitions over a
      large parametric space and two important topological phases, namely, quantum
      anomalous Hall (QAH) and quantum spin Hall (QSH) phases are found to coexist in
      the system, but they reside in different bandgaps. This new category of gap
      dependent QAH--QSH insulator paves the way for the possible observation of the
      coexistence of QSH and QAH effects at one platform.

PMID- 29328259
TI  - Ultra-high speed RF filtering switch based on stimulated Brillouin scattering.
AB  - Radio frequency (RF) filtering switch is highly desired for signal routing or
      manipulation in the RF system. Based on the stimulated Brillouin scattering
      effect and the electro-optics Pockels effect, we propose a novel RF filtering
      switch with a high-frequency filtering precision and a fast switching speed. We
      have experimentally demonstrated the RF filtering with a high precision of ~34 
      MHz, a wide operation bandwidth of ~18  GHz, and the RF switching at a speed of
      <100  ps, which is hundreds of times faster than the traditional RF switch.

PMID- 29328260
TI  - Fully digital programmable optical frequency comb generation and application.
AB  - We propose a fully digital programmable optical frequency comb (OFC) generation
      scheme based on binary phase-sampling modulation, wherein an optimized bit
      sequence is applied to phase modulate a narrow-linewidth light wave. Programming
      the bit sequence enables us to tune both the comb spacing and comb-line number
      (i.e., number of comb lines). The programmable OFCs are also characterized by
      ultra-flat spectral envelope, uniform temporal envelope, and stable bias-free
      setup. Target OFCs are digitally programmed to have 19, 39, 61, 81, 101, or 201
      comb lines and to have a 100, 50, 20, 10, 5, or 1 MHz comb spacing. As a
      demonstration, a scanning-free temperature sensing system using a proposed OFC
      with 1001 comb lines was also implemented with a sensitivity of 0.89 degrees
      C/MHz.

PMID- 29328261
TI  - Improved 2 * 2 Mach-Zehnder switching using coupled-resonator photonic-crystal
      nanobeams.
AB  - Design and simulation results are presented for an on-chip 2*2 Mach-Zehnder-based
      optical switch where each arm of the interferometer is composed of a coupled
      resonator optical waveguide. The individual resonators are one-dimensional
      photonic crystal nanobeam cavities, and switching occurs through thermally
      induced changes in the refractive index of the silicon structure using integrated
      heating pads. The performance of the coupled-resonator device is directly
      compared to its single resonator counterpart, and significant improvement is
      found in the bar-state CT metric.

PMID- 29328262
TI  - Wavelength-tunable Hermite-Gaussian modes and an orbital-angular-momentum-tunable
      vortex beam in a dual-off-axis pumped Yb:CALGO laser.
AB  - A dual-off-axis pumping scheme is presented to generate wavelength-tunable high
      order Hermite-Gaussian (HG) modes in Yb:CaGdAlO4 lasers. The mode and wavelength
      can be actively controlled by the off-axis displacements and pump power. The
      purities of the output HG modes are quantified by intensity distributions and the
      measured M2 values. The highest order reaches m=15 for stable HGm,0 mode, and
      wavelength-tunable width is about 10 nm. Moreover, through externally converting
      the HGm,0 modes, the vortex beams carrying orbital angular momentum (OAM) with a
      large OAM-tunable range from +/-1h to +/-15h are produced. This work is effective
      for largely scaling the spectral and OAM tunable ranges of optical vortex beams.

PMID- 29328263
TI  - Common-path spectral interferometry for single-shot terahertz electro-optics
      detection: publisher's note.
AB  - This publisher's note corrects an error in one of the authors' names and an error
      in one of the grant numbers in Opt. Lett.42, 4263 (2017).

PMID- 29328264
TI  - Mid-infrared supercontinuum generation from 1.6 to >11  MUm using concatenated
      step-index fluoride and chalcogenide fibers.
AB  - We demonstrate an all-fiber supercontinuum source that generates a continuous
      spectrum from 1.6 MUm to >11  MUm with 417 mW on-time average power at 33% duty
      cycle. By utilizing a master oscillator power amplifier pump with three
      amplification stages and concatenating solid core ZBLAN, arsenic sulfide, and
      arsenic selenide fibers, we shift 1550 nm light to ~4.5  MUm, ~6.5  MUm, and >11 
      MUm, respectively. With 69 mW past 7.5 MUm, this source provides both high power
      and broad spectral expansion, while outputting a single fundamental mode.

PMID- 29328265
TI  - In-fiber high-speed recognition of incoherent-light broadband energy spectrum
      patterns.
AB  - A fiber-optic system is proposed and experimentally demonstrated for real-time,
      on-the-fly identification of an incoherent-light energy spectrum pattern based on
      dispersion-induced time-spectrum convolution. In the proposed system, the
      incoming frequency-spectrum patterns to be identified are modulated by a time
      mapped version of the target intensity profile. Following propagation through a
      suitable fiber-optic dispersive medium, the measured output temporal waveform
      provides a correlation of the incoming spectra with the programmed target
      pattern. This enables direct, real-time detection of the matching energy spectra,
      without any further numerical post-processing. We experimentally demonstrate
      successful recognition of a target infrared spectral pattern, extending over a
      bandwidth of 1.5 THz with a resolution of ~12  GHz, with sub-megahertz update
      rates. A path for further performance improvements is also suggested.

PMID- 29328266
TI  - Nonlinear refractive index measurements using time-resolved digital holography.
AB  - In this Letter, a novel method to evaluate nonlinear refractive index using time
      resolved digital holographic microscopy is introduced. To demonstrate the
      viability of the method, cross-correlative nonlinear refractive index values for
      sapphire are measured experimentally: 2.75.10-20  m2/W at 1030 nm and 4.10.10-20 
      m2/W 515 nm wavelengths. The obtained results for sapphire are compared to
      those available in literature obtained by other methods.

PMID- 29328267
TI  - 25  W single-frequency, low noise fiber MOPA at 1120  nm.
AB  - This Letter reports on the development of a 25 W single-frequency, all-fiber
      master oscillator power amplifier (MOPA) operating at 1120 nm. By heating the
      gain fiber at 75 degrees C, an output power of 25.3 W is achieved with an optical
      to-optical efficiency of 53.5%. The output shows no sign of stimulated Brillouin
      scattering and the signal to amplified spontaneous emission ratio is close to 40
      dB. A M2 value of 1.15 and a polarization extinction ratio of 17 dB are measured.
      The relative intensity noise of the output is also characterized, reaching -155 
      dBc/Hz at 10 MHz at the maximum output power. The study of the noise dynamics
      highlights, for the first time to the best of our knowledge, an unpredicted
      behavior due to the strong backward amplified spontaneous emission.

PMID- 29328268
TI  - Backscatter particle image velocimetry via optical time-of-flight sectioning.
AB  - Conventional particle image velocimetry (PIV) configurations require a minimum of
      two optical access ports, inherently restricting the technique to a limited class
      of flows. Here, the development and application of a novel method of
      backscattered time-gated PIV requiring a single-optical-access port is described
      along with preliminary results. The light backscattered from a seeded flow is
      imaged over a narrow optical depth selected by an optical Kerr effect (OKE) time
      gate. The picosecond duration of the OKE time gate essentially replicates the
      width of the laser sheet of conventional PIV by limiting detected photons to a
      narrow time-of-flight within the flow. Thus, scattering noise from outside the
      measurement volume is eliminated. This PIV via the optical time-of-flight
      sectioning technique can be useful in systems with limited optical access and in
      flows near walls or other scattering surfaces.

PMID- 29328269
TI  - Generation of 400  MUW at 17.5  um using a two-color Yb fiber chirped pulse
      amplifier: erratum.
AB  - An Erratum is presented to correct the reported [Opt. Lett.36, 1080
      (2011)OPLEDP0146-959210.1364/OL.36.001080] power of the generated long
      wavelength, mid-infrared power.

PMID- 29328270
TI  - Ultrasensitive fiber tilt sensor based on a mobile inscribed microbubble along
      the arc-shaped inwall of the microcavity: publisher's note.
AB  - This publisher's note corrects an error in the funding section in Opt. Lett.42,
      4418 (2017).OPLEDP0146-959210.1364/OL.42.004418.

PMID- 29328271
TI  - Integrated diamond Raman laser pumped in the near-visible.
AB  - Using a high-Q diamond microresonator (Q>300,000) interfaced with high-power
      handling directly-written doped-glass waveguides, we demonstrate a Raman laser in
      an integrated platform pumped in the near-visible. Both TM-to-TE and TE-to-TE
      lasing is observed, with a Raman lasing threshold as low as 20 mW and Stokes
      power of over 1 mW at 120 mW pump power. Stokes emission is tuned over a 150 nm
      (60 THz) bandwidth of approximately 875 nm wavelength, corresponding to 17.5% of
      the center frequency.

PMID- 29328272
TI  - Direct laser writing combined with a phase-delay probe.
AB  - We develop on lithium niobate crystals a photorefractive direct-laser-writing
      approach, in which we combine in one beam both direct writing and phase-delay
      probing functionalities to extract the in situ information of the refractive
      index or the electrostatic field. The phase-delay signal, predicted well by the
      photorefractive theory, is used as feedback for tuning the exposure time or
      scanning speed of the focused laser in order to control the refractive index
      change (Deltan) at single points and scanning lines. Different features found in
      creating Deltan at the points and lines are explained by the different
      photorefractive responses in the two cases.

PMID- 29328273
TI  - Optothermal control of gains in erbium-doped whispering-gallery microresonators.
AB  - Erbium-doped whispering-gallery-mode (WGM) microcavities have great potential in
      many important applications, such as the precision detection and the micro/nano
      laser. However, they are sensitive to the fluctuations from the pump laser and
      the environment. Here we demonstrate the precise controlling of transmission
      spectra and optical gains using optothermal scanning methods in erbium-doped WGM
      microcavities. The transmission spectrum of the probe signal exhibits the
      transition between asymmetric Fano-like resonance and the Lorentz peak (or dip)
      through tuning the input frequency and the scanning speed of the pump laser. In
      particular, the analytical calculations can fit well with our experimental
      results through adiabatically eliminating the anticlockwise optical mode. This
      Letter shows that the optothermal control of gains is more robust to external
      noises, which paves a crucial step toward the application in the ultra-sensitive
      detection.

PMID- 29328274
TI  - Photonics-enabled compressive sensing with spectral encoding using an incoherent
      broadband source.
AB  - In this Letter, we propose an approach to achieving photonics-enabled compressive
      sensing of sparse wideband radio frequency signals in which an incoherent
      broadband source is applied, and the mixing and integration functions are
      realized in the optical domain. A spectrum shaper is employed to slice and encode
      the spectrum of the broadband light according to a predetermined random sequence.
      Because of the dispersion-induced group delay, the mixing between the incoming
      signal and the random bit sequence is achieved. At the output of the spectrum
      shaper, an array of photodetectors is employed to realize down-sampling, and the
      input sparse signal can be captured in a single-shot mode. Since no pulsed laser
      is employed, our scheme obviates the need for time-domain synchronization between
      the repetitive ultra-fast pulses and the random sequence. Experimental
      demonstrations and numerical results are presented to verify the feasibility and
      potential of the approach.

PMID- 29328275
TI  - Fabricated nanogap-rich plasmonic nanostructures through an optothermal surface
      bubble in a droplet.
AB  - A rapid and cost-effective method for the fabrication of nanogap-rich structures
      is demonstrated in this Letter. The method utilizes the Marangoni convection
      around an optothermal surface bubble inside a liquid droplet with a nanoliter
      volume. The liquid droplet containing metallic nanoparticles reduces the sample
      consumption and confines the liquid flow. The optothermal surface bubble creates
      a strong convective flow that allows for the rapid deposition of the metallic
      nanoparticles to form nanogap-rich structures on any substrate under ambient
      conditions. This method will enable a broad range of applications such as
      biosensing, environmental analysis, and nonlinear optics.

PMID- 29328276
TI  - Femto/nano-second switchable passively mode-locked fiber laser with analytic
      modeling by the cubic-quintic Ginzburg-Landau equation.
AB  - We report a passively mode-locked erbium-doped fiber laser with pulse widths
      switchable from 473 fs to 76.8 ns, where the fundamental mode-locking, noise-like
      pulse, nanosecond mode-locking, and dual-width mode-locking (DML) are obtained by
      adjusting a polarization controller. Co-existence of femto- and nano-second
      pulses in DML is attributed to the gain balancing. Analytic modeling of the fiber
      laser with the cubic-quintic Ginzburg-Landau equation is presented, in which the
      pulse widths are calculated as functions of dispersion, self-phase modulation
      (SPM), cubic saturable absorption (SA), and quintic SA. The generation of
      nanosecond pulses is caused by the weakened intracavity pulse-shortening
      strength, the reduced effective SPM, and the inclusion of quintic SA in the laser
      cavity.

PMID- 29328277
TI  - Efficient 1.7  MUm light source based on KTA-OPO derived by Nd:YVO4 self-Raman
      laser.
AB  - An intra-cavity optical parametric oscillator (OPO) emitting at 1.7 MUm derived
      by Nd:YVO4 self-Raman laser is demonstrated in this Letter, with a KTiOAsO4 (KTA)
      crystal used as nonlinear optical crystal. A laser diode end-pumped acousto-optic
      Q-switched Nd:YVO4 self-Raman laser at 1176 nm was employed as the pump source.
      At an incident pump power of 12.1 W and a pulse repetition frequency of 60 kHz,
      average output power up to 1.2 W signal light at 1742 nm was obtained, with diode
      to-signal conversion efficiency of 10%. The pulse width was about 11 ns and
      spectral line width was less than 0.5 nm for the signal light. The results show
      that compact intra-cavity KTA-OPO derived by Nd:YVO4 self-Raman laser is an
      efficient method for 1.7 MUm waveband laser generation, with potential
      applications in biological imaging, laser therapy, special materials processing,
      etc.

PMID- 29328279
TI  - Tunable mid-infrared source from an ultrafast two-color Yb:fiber chirped pulse
      amplifier: erratum.
AB  - This Erratum is presented to correct the reported [Opt. Lett.37, 3570 (2012)]
      power of the generated long wavelength, mid-infrared power.

PMID- 29328278
TI  - Controlled-phase manipulation module for orbital-angular-momentum photon states.
AB  - Phase manipulation is essential to quantum information processing, for which the
      orbital angular momentum (OAM) of photon is a promising high-dimensional
      resource. Dove prism (DP) is one of the most important elements to realize the
      nondestructive phase manipulation of OAM photons. DP usually changes the
      polarization of light and thus increases the manipulation error for a spin-OAM
      hybrid state. DP in a Sagnac interferometer also introduces a mode-dependent
      global phase to the OAM mode. In this work, we implemented a high-dimensional
      controlled-phase manipulation module (PMM), which can compensate the mode
      dependent global phase and thus preserve the phase in the spin-OAM hybrid
      superposition state. The PMM is stable for free running and is suitable to
      realize the high-dimensional controlled-phase gate for spin-OAM hybrid states.
      Considering the Sagnac-based structure, the PMM is also suitable for classical
      communication with the spin-OAM hybrid light field.

PMID- 29328280
TI  - Strategies for achieving intense single-cycle pulses with in-line post
      compression setups.
AB  - Intense few- and single-cycle pulses are powerful tools in different fields of
      science Today, third- and higher-order terms in the remnant spectral phase of the
      pulses remain a major obstacle for obtaining high-quality few- and single-cycle
      pulses from in-line post-compression setups. In this Letter, we show how input
      pulse shaping can successfully be applied to standard post-compression setups to
      minimize the occurrence of high-order phase components during nonlinear
      propagation and to directly obtain pulses with durations down to 3 fs.
      Furthermore, by combining this pulse shaping of the input pulse with new
      generation broadband chirped mirrors and material addition for remnant third
      order phase correction, pulses down to 2.2 fs duration have been measured.

PMID- 29328281
TI  - Thermally sensitive scattering of terahertz waves by coated cylinders for tunable
      invisibility and masking.
AB  - Temperature-sensitive scattering of terahertz (THz) waves by infinitely long,
      cylindrical core-shell structures was theoretically studied. Each structure is a
      dielectric cylinder coated with an InSb shell illuminated by either a transverse
      electric (TE) or a transverse-magnetic (TM) plane wave. InSb is a thermally
      tunable semiconductor showing a transition from dielectric to plasmonic state at
      THz frequencies. Accordingly, the total scattering efficiency (TSE) can be
      thermally tuned for both polarization states of the incident plane wave. The
      spectral locations of the maxima and minima of the TSE of an InSb-coated cylinder
      can be exploited for cloaking the core. At least three scenarios lead to the
      strong suppression of scattering by a single core-shell structure in different
      spectral regimes when the temperature is fixed. The excitation of localized
      surface-plasmon resonances is the feature being common for two of them, while the
      effect of volumetric resonance dominates in the third scenario. Regimes that are
      either highly or weakly sensitive to the core material were identified. Weak
      sensitivity enables masking, i.e., the core material cannot be identified by a
      far-zone observer. The TSE minima are usually significantly sensitive to the
      polarization state, but ones with weak sensitivity to the polarization state also
      exist.

PMID- 29328282
TI  - Recommended conceptual optical system design for China's Large Optical-infrared
      Telescope (LOT).
AB  - Recently, China is planning to construct a new large optical-infrared telescope
      (LOT), in which the aperture of the primary mirror is as large as 12m. China's
      LOT is a general-purpose telescope, which is aimed to work with multiple
      scientific instruments such as spectrographs. Based on the requirements of LOT
      telescope, we have compared the performance of Ritchey-Chretien (RC) design and
      Aplanatic-Gregorian (AG) design from the perspective of scientific performance
      and construction cost. By taking the primary focal ratio, Nasmyth focal ratio,
      and telescope's site condition into consideration, we finally recommend a RC
      f/1.6 design configuration for LOT's Nasmyth telescope system. Unlike the general
      identical configuration, we choose a non-identical configuration for the
      telescope system which has a shorter Cassegrain focal ratio compared to the
      designed Nasmyth focal ratio. The non-identical design can allow for a shorter
      back focal distance and therefore a shorter telescope fork to guarantee the
      gravitational stability of the whole telescope structure, as well as relatively
      lower construction cost. Detailed analysis for the feasibility of our recommended
      design is provided in this paper.

PMID- 29328283
TI  - Tailoring the quality factors and nonlinear response in hybrid plasmonic
      dielectric metasurfaces.
AB  - Plasmonic nanoantennas and metamaterials concentrate optical energy into
      nanometric volumes strongly enhancing the light-matter interaction. This makes
      them promising platforms for optical sensing, nonlinear effects and quantum
      optics. However, absorption losses and radiative damping result in broad, low
      quality factor (Q) resonances of plasmonic systems that significantly limit their
      performance. Here, we develop a hybrid plasmonic/dielectric metasurface that can
      simultaneously achieve high Q and large field enhancement values in the near
      infrared by forming a hybridized mode between the nanoantennas' plasmonic mode
      and the photonic waveguide mode of Si device layer. The tunability of the modes
      and quality factors of our platform allows us to study the effect of the
      geometric parameters on the optical properties of the metasurface. We demonstrate
      that the strongest near field enhancement and nonlinear signal generation can be
      achieved by balancing the high Q factors and in-coupling efficiency in hybrid
      resonators.

PMID- 29328284
TI  - Improving the performance of hollow fiber surface plasssmon resonance sensor with
      one dimensional photonic crystal structure.
AB  - A high performance hollow fiber (HF) surface plasmon resonance (SPR) sensor
      utilizing one-dimensional photonic crystal (1DPC) is proposed. The performance of
      the designed sensor is analyzed theoretically with respect to the center
      wavelength and the bilayer period. Because the light transmitted in the sensor
      mostly have large incident angles, the center wavelength of the 1DPC should shift
      to longer wavelength to ensure the band gap covers the spectrum range of the
      incident light. The sensor exhibits better performance when the detection
      spectral range is located in the band gap of 1DPC for incident angle larger than
      80 degrees . Compared to conventional HF SPR sensor, the figure of merit (FOM) of
      the proposed sensor is three to four times higher while the sensitivity is
      comparable. Moreover, within the limited spectrum range of 400 to 800nm, the
      proposed sensor have much wider refractive index (RI) detection range and can
      detect sensed medium with low RI very close to the supporting tube.

PMID- 29328285
TI  - Astigmatic laser beams with a large orbital angular momentum.
AB  - We show that an elliptic Gaussian beam, focused by a cylindrical lens, can be
      represented as a linear combination of a countable number of only even angular
      harmonics with both positive and negative topological charge. For the orbital
      angular momentum (OAM) of the astigmatic Gaussian beam, an exact expression is
      obtained in a form of a converging series of the Legendre functions of the second
      kind. It is shown that at some conditions only the terms with the positive or
      negative topological charge are remained in this series. Using a hybrid numeric
      experimental approach, we obtained the normalized OAM of the astigmatic beam,
      equal to 109, which is just 6% different from the exact OAM of 116, calculated by
      the equation. To generate such laser beams, there is no need in special optical
      elements such as spiral phase plates. The OAM of such beams can be adjusted by
      varying the waist radius of the Gaussian beam and the focal length of the
      cylindrical lens. The OAM of such beams can reach large values.

PMID- 29328286
TI  - Information-weighted constrained regularization for particle size distribution
      recovery in multiangle dynamic light scattering.
AB  - In particle size measurement with dynamic light scattering (DLS), it is difficult
      to get an accurate recovery of a bimodal particle size distribution (PSD) with a
      peak position ratio less than ~2:1, especially when large particles (>350nm) are
      present. This is due to the inherent noise in the autocorrelation function (ACF)
      data and the scarce utilization of PSD information during the inversion process.
      In this paper, the PSD information distribution in the ACF data is investigated.
      It was found that the initial decay section of the ACF contains more information,
      especially for a bimodal PSD. Based on this, an information-weighted constrained
      regularization (IWCR) method is proposed in this paper and applied in multiangle
      DLS analysis for bimodal PSD recovery. By using larger (or smaller) coefficients
      for weighting the ACF data, more (or less) weight can then be given to the
      initial part of the ACF. In this way, the IWCR method can enhance utilization of
      the PSD information in the ACF data, and effectively weaken the effect of noise
      at large delay time on PSD recovery. Using this method, bimodal PSDs (with
      nominal diameters of 400:608 nm, 448:608 nm, 500:600 nm) were recovered
      successfully from simulated data and it appears that the IWCR method can improve
      the recovery resolution for closely spaced bimodal particles. Results of the PSD
      recovery from experimental DLS data confirm the performance of this method.

PMID- 29328287
TI  - Method for precise evaluation of refractive index modulation amplitude inside the
      volume Bragg grating recorded in photo-thermo-refractive glass.
AB  - In this paper, we present a method for achieving precise evaluation of amplitude
      of refractive index modulation (RIM) inside the volume Bragg grating (VBG)
      recorded in photo-thermo-refractive (PTR) glasses. The Gaussian divergence
      characteristics of the incident beam is theoretically considered when calculating
      the angular selectivity of VBG, and the profiles of experimental angular
      selectivity curves are utilized to determine the value of RIM with one step. The
      effectiveness of our proposed method is experimentally verified. This method is
      applicable even if the full width at half maximum (FWHM) of VBG's angular
      selectivity curve has the same order of magnitude as or is less than the beam
      divergence.

PMID- 29328288
TI  - Invisible gateway for both light waves and rays.
AB  - Considering that previous invisible gateways (an open entrance that only blocks
      electromagnetic waves) based on super-scatters designed by transformation optics
      cannot effectively work for narrow beams and light rays that do not touch
      negative refractive index material, we explore a new way to realize an improved
      invisible gateway that can give a good performance for both light waves and rays.
      In all previous invisible gateways, they require a finite thickness of the wall
      and the gateway. For the improved invisible gateway proposed in this study, there
      is no requirement on the thickness of the wall and gateway, i.e. the wall and
      gateway can be infinitely thin. Our study will go a further step to realize the
      invisible gateway in fiction.

PMID- 29328289
TI  - Electrical switching of birefringence in zirconium phosphate colloids with
      various solvents.
AB  - Even though a graphene-oxide (GO) dispersion is attractive for electro-optical
      switching devices because of its high Kerr coefficient, it has several
      limitations such as chemical instability and optical loss due to absorption at
      visible wavelengths. Here we introduce the use of tetrabutylammonium-tethered
      alpha-zirconium phosphate (TBA-ZrP) colloid in various solvents for electro
      optical switching devices; the TBA-ZrP colloid is chemically stable and optically
      transparent. We find that the electrical switching behavior of TBA-ZrP is
      sensitively dependent on the type of solvent. The TBA-ZrP colloid in acetone
      exhibits the highest effective Kerr coefficient and the fastest switching time,
      which is related to the unusual behavior of the viscosity of the TBA-ZrP colloid
      in acetone. Its viscosity is relatively low and less sensitive to concentration
      compared to ZrP in other solvents. This indicates that the motion of individual
      nanoparticles is relatively less restricted in acetone. These findings may be
      useful in developing electro-optical devices using lyotropic liquid crystal
      colloids.

PMID- 29328290
TI  - Design of narrowband Bragg spectral filters in subwavelength grating metamaterial
      waveguides.
AB  - Properties of reflection and transmission spectral filters based on Bragg
      gratings in subwavelength grating (SWG) metamaterial waveguides on silicon-on
      insulator platform have been analyzed using proprietary 2D and 3D simulation
      tools based on Fourier modal method and the coupled-mode theory. We also
      demonstrate that the coupled Bloch mode theory can be advantageously applied to
      design of Bragg gratings in SWG waveguides. By combining different techniques,
      including judiciously positioning silicon loading segments within the evanescent
      field of the SWG waveguide and making use of its dispersion properties, it is
      possible to attain sub-nanometer spectral bandwidths for both reflection and
      transmission filters in the wavelength range of 1550 nm while keeping minimum
      structural features of the filters as large as 100 nm. Numerical simulations have
      also shown that a few nanometer jitter in the size and position of Si segments is
      well tolerated in our filter designs.

PMID- 29328291
TI  - Whispering gallery modes in a single silica microparticle attached to an optical
      microfiber and their application for highly sensitive displacement sensing.
AB  - A compact and relatively stable structure is experimentally demonstrated to
      excite whispering gallery modes (WGMs) in a single chemically fabricated silica
      microparticles with a diameter of around 10.6 MUm attached to an optical
      microfiber. The resonance dip with an extinction ratio of 14 dB and Q factor of
      around 300 has been achieved. Based on the WGMs in this structure, an in-line
      fiber-optic displacement sensor is presented with a high sensitivity of 33 dB/mm
      and a measurement range of over 400 MUm. The measurement resolution of this
      displacement sensor can reach to ~10 MUm. The good reversibility and
      repeatability are also verified. This work offers a scheme to observe the WGMs in
      a single silica microparticles and demonstrates their application for in-line
      highly-sensitive displacement sensing.

PMID- 29328292
TI  - Experimental observation of quantum state-independent contextuality under no
      signaling conditions.
AB  - Contextuality, the impossibility of assigning context-independent measurement
      outcomes, is a critical resource for quantum computation and communication. No
      signaling between successive measurements is an essential requirement that should
      be accomplished in any test of quantum contextuality and that is difficult to
      achieve in practice. Here, we introduce an optimal quantum state-independent
      contextuality inequality in which the deviation from the classical bound is
      maximal. We then experimentally test it using single photons generated from a
      defect in a bulk silicon carbide, while satisfying the requirement of no
      signaling within the experimental error. Our results shed new light on the study
      of quantum contextuality under no-signaling conditions.

PMID- 29328293
TI  - Whispering gallery mode resonator sensor for in situ measurements of hydrogel
      gelation.
AB  - Whispering gallery mode (WGM) resonators are compact and ultrasensitive devices,
      which enable label-free sensing at the single-molecule level. Despite their high
      sensitivity, WGM resonators have not been thoroughly investigated for use in
      dynamic biochemical processes including molecular diffusion and polymerization.
      In this work, the first report of using WGM sensors to continuously monitor a
      chemical reaction (i.e. gelation) in situ in a hydrogel is described.
      Specifically, we monitor and quantify the gelation dynamics of polyacrylamide
      hydrogels using WGM resonators and compare the results to an established
      measurement method based on rheology. Rheology measures changes in
      viscoelasticity, while WGM resonators measure changes in refractive index.
      Different gelation conditions were studied by varying the total monomer
      concentration and crosslinker concentration of the hydrogel precursor solution,
      and the resulting similarities and differences in the signal from the WGM
      resonator and rheology are elucidated. This work demonstrates that WGM alone or
      in combination with rheology can be used to investigate the gelation dynamics of
      hydrogels to provide insights into their gelation mechanisms.

PMID- 29328294
TI  - State-switchable and wavelength-tunable gain-switched mid-infrared fiber laser in
      the wavelength region around 2.94 MUm.
AB  - We demonstrate a gain-switched singly Ho3+-doped ZBLAN fiber laser for the first
      time in the wavelength region around 2.94 MUm which circumvents the strong water
      vapor lines. Four switchable gain-switched temporal states with 1/n (n = 4,3,2,1)
      pump repetition rates are first observed. The influences of pump power (pulse
      energy), repetition rate, duty cycle (pulse duration), and laser wavelength on
      their characteristics are studied, respectively. The results indicate that high
      pump repetition rate, large pump duty cycle, and short laser wavelength are
      beneficial for obtaining more gain-switched temporal states. For the case (n =
      1), the increased pump repetition rate contributes to the increased pulse
      duration while decreased pulse energy and peak power. While MUs-level pump pulse
      duration variation has an almost negligible effect on them. By introducing a
      plane ruled grating, the wavelength tuning was performed yielding a tuning range
      of 105 nm from 2895.5 nm to 3000.5 nm which just overlays the peak region of
      liquid water absorption. Finally, further optimizing of laser performances is
      discussed as well. This demonstration is helpful for preliminarily designing,
      prior to constructing a mid-infrared gain-switched laser which can find direct
      applications in laser surgery.

PMID- 29328295
TI  - Bright nanowire single photon source based on SiV centers in diamond.
AB  - The practical implementation of many quantum technologies relies on the
      development of robust and bright single photon sources that operate at room
      temperature. The negatively charged silicon-vacancy (SiV-) color center in
      diamond is a possible candidate for such a single photon source. However, due to
      the high refraction index mismatch to air, color centers in diamond typically
      exhibit low photon out-coupling. An additional shortcoming is due to the random
      localization of native defects in the diamond sample. Here we demonstrate
      deterministic implantation of Si ions with high conversion efficiency to single
      SiV- centers, targeted to fabricated nanowires. The co-localization of single SiV
      centers with the nanostructures yields a ten times higher light coupling
      efficiency than for single SiV- centers in bulk diamond. This enhanced photon out
      coupling, together with the intrinsic scalability of the SiV- creation method,
      enables a new class of devices for integrated photonics and quantum science.

PMID- 29328296
TI  - Laser heterodyne interferometer with rotational error compensation for precision
      displacement measurement.
AB  - A laser heterodyne interferometer with rotational error compensation is proposed
      for precision displacement measurement. In this interferometer, the rotational
      error of the measured object is obtained by using an angle detecting unit which
      is composed of a semi-reflective film, a polarizing beam splitter, a quarter-wave
      plate, a convex lens and a two-dimensional position sensitive detector. And the
      obtained rotational angle is used for compensating its influence on displacement
      measurement result. The optical configuration of the proposed interferometer is
      designed, and the mathematical model for displacement measurement with rotational
      error compensation is established. The coupling effect of axial displacement on
      rotational angle measurement and the rotational angle range used for compensation
      on displacement measurement are discussed in detail. To verify feasibility of the
      proposed interferometer, the experimental setup was constructed and several
      verification experiments were performed.

PMID- 29328297
TI  - Detecting fast signals beyond bandwidth of detectors based on computational
      temporal ghost imaging.
AB  - Measurement of fast signal is getting more and more important in many fields. In
      this paper, we propose to detect a temporal signal based on the idea of
      computational ghost imaging (GI), which can greatly reduce requirements on
      bandwidth of detectors. In experiments, we implement retrieving of a temporal
      signal with time scale of 50ns using a detector of 1kHz bandwidth, which is much
      lower than the requirement on bandwidth of detector according to information
      theory. The performance of our technique are also investigated under different
      detection bandwidths.

PMID- 29328298
TI  - Instantaneous one-angle white-light scatterometer.
AB  - We present a white light scatterometer operating at a unique scattering
      direction. Mechanical motions and wavelength scans are removed. The technique
      provides an immediate flexible characterization of roughness with no loss of
      resolution.

PMID- 29328299
TI  - Coherent modulation up to 100 GBd 16QAM using silicon-organic hybrid (SOH)
      devices.
AB  - We demonstrate the generation of higher-order modulation formats using silicon
      based inphase/quadrature (IQ) modulators at symbol rates of up to 100 GBd. Our
      devices exploit the advantages of silicon-organic hybrid (SOH) integration, which
      combines silicon-on-insulator waveguides with highly efficient organic electro
      optic (EO) cladding materials to enable small drive voltages and sub-millimeter
      device lengths. In our experiments, we use an SOH IQ modulator with a pi-voltage
      of 1.6 V to generate 100 GBd 16QAM signals. This is the first time that the 100
      GBd mark is reached with an IQ modulator realized on a semiconductor substrate,
      leading to a single-polarization line rate of 400 Gbit/s. The peak-to-peak drive
      voltages amount to 1.5 Vpp, corresponding to an electrical energy dissipation in
      the modulator of only 25 fJ/bit.

PMID- 29328300
TI  - Effects of edge inclination angles on whispering-gallery modes in printable wedge
      microdisk lasers.
AB  - The ink-jet technique was developed to print the wedge polymer microdisk lasers.
      The characterization of these lasers was implemented using a free-space optics
      measurement setup. It was found that disks of larger edge inclination angles have
      a larger free spectral range (FSR) and a lower resonance wavelength difference
      between the fundamental transverse electric (TE) and transverse magnetic (TM)
      whispering-gallery modes (WGMs). This behavior was also confirmed with
      simulations based on the modified Oxborrow's model with perfectly matched layers
      (PMLs), which was adopted to accurately calculate the eigenfrequencies, electric
      field distributions, and quality parameters of modes in the axisymmetric
      microdisk resonators. Combined with the nearly equivalent quality factor (Q
      factor) and finesse factor (F-factor) variations, the correlations between the TE
      and left adjacent TM modes were theoretically demonstrated. When the edge
      inclination angle is varied, the distinguishable mode distribution facilitates
      the precise estimation of a resonance wavelength shift. Therefore, the flexible
      and efficient nature of wedge polymer microdisk lasers extends their potential
      applications in precision sensing technology.

PMID- 29328301
TI  - Coherence-resolution relationship in holographic and coherent diffractive
      imaging.
AB  - We study by numerical simulation how spatial coherence affects the reconstruction
      quality of images in coherent diffractive x-ray imaging. Using a conceptually
      simple, but computationally demanding approach, we have simulated diffraction
      data recorded under partial coherence, and then use the data for iterative
      reconstruction algorithms using a support constraint. By comparison of
      experimental regimes and parameters, we observe a significantly higher robustness
      against partially coherent illumination in the near-field compared to the far
      field setting.

PMID- 29328302
TI  - Sliding sensor using fiber Bragg grating for mechanical fingers.
AB  - A sliding sensor based on a fiber Bragg grating (FBG) was proposed to enable
      mechanical fingers to softly grasp an object. FBG strain sensors are embedded in
      a polymeric material as a sensing element to obtain sliding information. This
      study expounded the structural design of the sliding sensor and the mechanism of
      sliding sensation, which were verified using the finite element simulation. The
      static and dynamic performances of the sliding sensor were studied
      experimentally. Finally, the sensing signals were processed using fuzzy logic.
      Results show that the FBG sliding sensor with a simple structure has high
      sensitivity and can reliably detect the contact state of the target object,
      thereby providing a design scheme for the study of the sliding sense of
      mechanical fingers.

PMID- 29328303
TI  - Tunable and channel spacing precisely controlled comb filters based on the fused
      taper technology.
AB  - We propose and demonstrate an adjustable all-fiber comb filter with precisely
      controlled channel spacing by employing a tapered fiber in one arm of a Mach
      Zehnder interferometer (MZI) for the first time. Using fused taper technology to
      draw the fiber, we can precisely control the optical path difference between the
      two arms of the MZI, thus realizing a precisely controllable channel spacing. By
      rotating the polarization controller state in the other arm of the MZI, the
      transmission spectrum wavelength can be continuously tuned. Comb filters with
      controllable channel spacings from 0.2 to 3.0 nm have been numerically studied
      and achieved in experiment. Applications of a filter based on a multi-wavelength
      tunable all-fiber laser source are also demonstrated.

PMID- 29328304
TI  - Optofluidic refractive-index sensors employing bent waveguide structures for low
      cost, rapid chemical and biomedical sensing.
AB  - We propose and develop an intensity-detection-based refractive-index (RI) sensor
      for low-cost, rapid RI sensing. The sensor is composed of a polymer bent ridge
      waveguide (BRWG) structure on a low-cost glass substrate and is integrated with a
      microfluidic channel. Different-RI solutions flowing through the BRWG sensing
      region induce output optical power variations caused by optical bend losses,
      enabling simple and real-time RI detection. Additionally, the sensors are
      fabricated using rapid and cost-effective vacuum-less processes, attaining the
      low cost and high throughput required for mass production. A good RI solution of
      5.31 10-4 * RIU-1 is achieved from the RI experiments. This study demonstrates
      mass-producible and compact RI sensors for rapid and sensitive chemical analysis
      and biomedical sensing.

PMID- 29328305
TI  - Analysis of photonic noise generated due to Kerr nonlinearity in silicon ring
      resonators.
AB  - The Kerr effect in silicon ring resonators (RRs) is widely used for switching and
      regeneration of optical communications signals. In addition, it has been shown to
      considerably limit the performance of refractive index sensors based on high
      quality-factor RRs. While the Kerr effect's impact on output signals of silicon
      RRs is well known, its influence on the properties of the output noise is yet to
      be explored. In this work, we analytically and numerically analyze the noise
      properties of Kerr effect in silicon RRs. We show that the input power, RR's
      bandwidth, and input optical signal to noise ratio (OSNR) have significant
      influence on the power and distribution of the output noise. We use the developed
      noise model to evaluate the RR's noise figure and output noise distribution for
      optical communications and sensing applications. These noise properties can be
      used for the design and performance evaluation of optical communications systems
      and sensors using silicon photonic RRs.

PMID- 29328306
TI  - Compensation factors for 3rd order coma in three mirror anastigmatic (TMA)
      telescopes.
AB  - Misalignment induced third-order coma with respect to misaligned parameters in
      TMA optical systems is derived by using Nodal Aberration Theory, which yields the
      compensation factors that can be used to accomplish coma compensation in both
      coaxial and off-axis misaligned TMA telescopes. By using the compensation
      factors, coma free point for the tertiary mirror in TMA telescopes is derived and
      proved to be the negative form of the one for the secondary mirror in the
      Cassegrain telescope. The compensation factors can also be used to design the off
      axis TMAs due to their capability of eliminating the coma over the field of view.

PMID- 29328307
TI  - Channel estimation for wideband underwater visible light communication: a
      compressive sensing perspective.
AB  - With the rapid development of light emitting diode (LED), visible light
      communication (VLC) becomes an important technique for information transmission
      including underwater applications. However, accurate channel estimation for
      underwater VLC is still challenging due to the complex environment of the
      underwater VLC channel. In this paper, by utilizing a proper approximation, where
      the channel attenuation is linear with the frequency, a new compressive sensing
      (CS) based channel estimation approach is proposed. Utilizing the sparse property
      of the reflection path length for the underwater VLC channel, the CS framework is
      modeled to estimate the reflection path length, which can further recover the
      underwater VLC channel. Moreover, a Bayesian CS recovery algorithm is
      investigated to overcome the problem of high coherence for the sensing matrix
      which outperforms the conventional greedy algorithm such as orthogonal matching
      pursuit (OMP). Simulation results illustrate that our proposed channel estimation
      for underwater VLC systems has a superior performance which can significantly
      reduce the pilot overhead, improve the spectral efficiency, and enhance the
      estimation accuracy.

PMID- 29328308
TI  - Large enhancement of second harmonic generation from transition-metal
      dichalcogenide monolayer on grating near bound states in the continuum.
AB  - Second harmonic generation from the two-layer structure where a transition-metal
      dichalcogenide monolayer is put on a one-dimensional grating has been studied.
      This grating supports bound states in the continuum which have no leakage lying
      within the continuum of radiation modes, we can enhance the second harmonic
      generation from the transition-metal dichalcogenide monolayer by more than four
      orders of magnitude based on the critical field enhancement near the bound states
      in the continuum. In order to complete this calculation, the scattering matrix
      theory has been extended to include the nonlinear effect and the scattering
      matrix of a two-dimensional material including nonlinear terms; furthermore, two
      methods to observe the bound states in the continuum are considered, where one is
      tuning the thickness of the grating and the other is changing the incident angle
      of the electromagnetic wave. We have also discussed various modulation of the
      second harmonic generation enhancement by adjusting the azimuthal angle of the
      transition-metal dichalcogenide monolayer.

PMID- 29328309
TI  - Role of interactions in the magneto-plasmonic response at the geometrical
      threshold of surface continuity: publisher's note.
AB  - This publisher's note amends the author listing of [Opt. Express26, 32792
      (2017)].

PMID- 29328310
TI  - Distribution of a phase-stabilized 100.02 GHz millimeter-wave signal over a 160
      km optical fiber with 4.1 * 10-17 instability.
AB  - We report a long-distance phase-stabilized millimeter-wave distribution over
      optical fibers, where the optical-link-induced phase noise is compensated with a
      high-precision photonic-generated millimeter-wave (mm-wave) voltage-controlled
      oscillator (VCO). The mm-wave VCO is realized based on pre-filtering and re
      modulating optical spectral lines of an optical frequency comb (OFC). By
      adjusting the frequency spacing of the optical spectral lines extracted from the
      OFC, the phase error of the transmitted optical mm-wave signal can be compensated
      precisely. Using the mm-wave VCO, we demonstrate a distribution of a 100.02 GHz
      signal over spooled optical fibers and the fractional frequency instability of
      the system at different transmission distances is exhibited. The residual phase
      noise of the remote mm-wave signal after being transferred through a 160-km fiber
      link is measured to be -59 dBc/Hz at 1 Hz frequency offset from the carrier, and
      the RMS timing jitter in the frequency range from 0.01 Hz to 1 MHz reaches 62 fs.
      The long-term fractional frequency instability of 4.1 * 10-17 at 10000 s
      averaging time is achieved, and the maximum timing drift is within 0.93 ps (peak
      to peak) during 4 hours.

PMID- 29328311
TI  - Status analysis of keyhole bottom in laser-MAG hybrid welding process.
AB  - The keyhole status is a determining factor of weld quality in laser-metal active
      gas arc (MAG) hybrid welding process. For a better evaluation of the hybrid
      welding process, three different penetration welding experiments: partial
      penetration, normal penetration (or full penetration), and excessive penetration
      were conducted in this work. The instantaneous visual phenomena including
      metallic vapor, spatters and keyhole of bottom surface were used to evaluate the
      keyhole status by a double high-speed camera system. The Fourier transform was
      applied on the bottom weld pool image for removing the image noise around the
      keyhole, and then the bottom weld pool image was reconstructed through the
      inverse Fourier transform. Lastly, the keyhole bottom was extracted from the de
      noised bottom weld pool image. By analyzing the visual features of the laser-MAG
      hybrid welding process, mechanism of the closed and opened keyhole bottom were
      revealed. The results show that the stable opened or closed status of keyhole
      bottom is directly affected by the MAG droplet transition in the normal
      penetration welding process, and the unstable opened or closed status of keyhole
      bottom would appear in excessive penetration welding and partial penetration
      welding. The analysis method proposed in this paper could be used to monitor the
      keyhole stability in laser-MAG hybrid welding process.

PMID- 29328312
TI  - Highly sensitive temperature sensor using packaged optical microfiber coupler
      filled with liquids.
AB  - A novel temperature sensor based on a Teflon capillary encapsulated 2 * 2 optical
      microfiber coupler (OMC) filled with refractive index matching liquids is
      described. The sealed capillary and the filling liquid are demonstrated to
      enhance the temperature sensing performance, achieving a high temperature
      sensitivity of 5.3 nm/ degrees C. To the best of our knowledge, the temperature
      sensor described in this article exhibits the highest sensitivity among the OMC
      structure based fiber optic temperature sensors. Experimental results also show
      that it has good repeatability along with a fast response time of 243 ms.

PMID- 29328313
TI  - Achievable information rate enhancement of visible light communication using
      probabilistically shaped OFDM modulation.
AB  - We present the first experimental demonstration of orthogonal frequency division
      multiplexed (OFDM) modulation using the probabilistic shaping (PS) technique in
      visible light communication (VLC) systems, in order to increase the achievable
      information rate (AIR) according to the pre-estimated signal to noise ratio (SNR)
      of VLC channel. We numerically investigate the performance of PS technique and
      make a fair comparison with bit-loading technique under different scenarios. By
      using a phosphor-LED based VLC system with available bandwidth of ~45-MHz, OFDM
      with PS technique can experimentally realize an AIR of 204.1-Mb/s over 1-m free
      space transmission, leading to a 26.8% increment in comparison with OFDM using
      bit-loading technique at the expense of 16% overall forward error correction
      (FEC) overhead (OH).

PMID- 29328314
TI  - RF injection locked 18 GHz regeneratively mode-locked semiconductor laser.
AB  - In this manuscript, a semiconductor based fiber ring cavity mode-locked laser
      regeneratively driven at 18 GHz is presented. The optical spectrum of the laser
      is centered at 1578 nm. The laser is RF injection locked via an external source
      at 18 GHz. The phase noise of the mode-locked laser is measured and the
      integrated timing jitter was found to be 10.8 fs (from 100 Hz to 20 MHz) and 13.3
      fs (from 100 Hz to Nyquist frequency). The integrated amplitude fluctuation (from
      100 Hz to 20 MHz) was less than 0.02%. The laser phase and amplitude noise
      responses to various injected RF power levels were also investigated. The
      injection RF power has significant effect on the phase noise and the best jitter
      value is around 40 dB lower than the cavity regenerated RF power.

PMID- 29328316
TI  - Optimized phase sensing in a truncated SU(1,1) interferometer.
AB  - Homodyne detection is often used for interferometers based on nonlinear optical
      gain media. For the configuration of a seeded, "truncated SU(1,1)" interferometer
      Anderson, et al. [ Phys. Rev. A95, 063843 (2017)] showed how to optimize the
      homodyne detection scheme and demonstrated theoretically that it can saturate the
      quantum Cramer-Rao bound for phase estimation. In this work we extend those
      results by taking into account loss in the truncated SU(1,1) interferometer and
      determining the optimized homodyne detection scheme for phase measurement.
      Further, we build a truncated SU(1,1) interferometer and experimentally
      demonstrate that this optimized scheme achieves a reduction in noise level,
      corresponding to an enhanced potential phase sensitivity, compared to a typical
      homodyne detection scheme for a two-mode squeezed state. In doing so, we also
      demonstrate an improvement in the degree to which we can beat the standard
      quantum limit with this device.

PMID- 29328315
TI  - Magnetometry for precision measurement using frequency-modulation microwave
      combined efficient photon-collection technique on an ensemble of nitrogen-vacancy
      centers in diamond.
AB  - Sensitivity of magnetometers that use color centers is limited by poor photon
      collection and detection efficiency. In this paper, we present the details of a
      newly developed all-optical collection combined frequency-modulated microwave
      method. The proposed method achieves a high sensitivity in static magnetic-field
      detection both theoretically and experimentally. First, we demonstrate that this
      collection technique enables both a fluorescence collection as high as 40% and an
      efficient pump absorption. Subsequently, we exploit the optically detected
      magnetic resonance (ODMR) signal and quantitative magnetic detection of an
      ensemble of nitrogen vacancy (NV) centers, by applying a frequency-modulated (FM)
      microwave method followed by a lock-in technique on the resonance frequency
      point. Based on the results obtained using all-optical collection combined FM
      microwaves, we verified that the sensitivity of the magnetometer can achieve
      approximately 14 nT/?Hz at 1 Hz, using a discrete Fourier transform detection
      method experimentally. This method provides a compact and portable precision
      sensor platform for measuring magnetic fields, and is of interest for fundamental
      studies in spintronics.

PMID- 29328317
TI  - Planar polarization-routing optical cross-connects using nematic liquid crystal
      waveguides.
AB  - This paper presents the device design and performance analysis of a novel design
      of planar optical cross-connect (OXC) using nematic liquid crystal (NLC)
      waveguides. It employs N * N switching matrix in cross-bar fabric. In each unit
      cell, the input light is set in either the transverse electric (TE) mode or the
      transverse magnetic (TM) mode by electrically reorienting the NLC in the
      waveguide. The light then enters a passive waveguide and is routed to different
      paths depending on the polarization state (TE/TM mode). A sample device of 8 * 8
      OXC is analyzed for performance estimation, which predicts a maximum on-chip
      insertion loss of 3 dB, an average cross-talk of -40 dB, ~1 ms switching time,
      and 2 mm * 2 mm footprint. The proposed OXC is unique in the switching mechanism
      of polarization-dependent routing and allows non-blocking switching with high
      compactness and broad bandwidth. It is potential for optical circuit switching in
      data centers and optical communication networks.

PMID- 29328318
TI  - Efficient continuous-wave and passively Q-switched pulse laser operations in a
      diffusion-bonded sapphire/Er:Yb:YAl3(BO3)4/sapphire composite crystal around 1.55
      MUm.
AB  - A composite crystal consisting of a 1.5-mm-thick Er:Yb:YAl3(BO3)4 crystal between
      two 1.2-mm-thick sapphire crystals was fabricated by the thermal diffusion
      bonding technique. Compared with a lone Er:Yb:YAl3(BO3)4 crystal measured under
      the identical experimental conditions, higher laser performances were
      demonstrated in the sapphire/Er:Yb:YAl3(BO3)4/sapphire composite crystal due to
      the reduction of the thermal effects. End-pumped by a 976 nm laser diode in a
      hemispherical cavity, a 1.55 MUm continuous-wave laser with a maximum output
      power of 1.75 W and a slope efficiency of 36% was obtained in the composite
      crystal when the incident pump power was 6.54 W. Passively Q-switched by a
      Co2+:MgAl2O4 crystal, a 1.52 MUm pulse laser with energy of 10 MUJ and repetition
      frequency of 105 kHz was also realized in the composite crystal. Pulse width was
      315 ns. The results show that the sapphire/Er:Yb:YAl3(BO3)4/sapphire composite
      crystal is an excellent active element for 1.55 MUm laser.

PMID- 29328319
TI  - Dynamic spatial filtering using a digital micromirror device for high-speed
      optical diffraction tomography.
AB  - Optical diffraction tomography (ODT) is an emerging microscopy technique for
      three-dimensional (3D) refractive index (RI) mapping of transparent specimens.
      Recently, the digital micromirror device (DMD) based scheme for angle-controlled
      plane wave illumination has been proposed to improve the imaging speed and
      stability of ODT. However, undesired diffraction noise always exists in the
      reported DMD-based illumination scheme, which leads to a limited contrast ratio
      of the measurement fringe and hence inaccurate RI mapping. Here we present a
      novel spatial filtering method, based on a second DMD, to dynamically remove the
      diffraction noise. The reported results illustrate significantly enhanced image
      quality of the obtained interferograms and the subsequently derived phase maps.
      And moreover, with this method, we demonstrate mapping of 3D RI distribution of
      polystyrene beads as well as biological cells with high accuracy. Importantly,
      with the proper hardware configuration, our method does not compromise the 3D
      imaging speed advantage promised by the DMD-based illumination scheme.
      Specifically, we have been able to successfully obtain interferograms at over 1
      kHz speed, which is critical for potential high-throughput label-free 3D image
      cytometry applications.

PMID- 29328320
TI  - Efficient and tunable strip-to-slot fundamental mode coupling.
AB  - We present a novel photonic wire-to-slot waveguide coupler in SOI. The phase
      matching between a wire and slot mode is achieved using a mode transformer. The
      architecture consists of a balanced 50/50 power splitter and a tunable phase
      matched taper combiner forming a slot waveguide. We show a theoretical wire-to
      slot coupling efficiency of 99 % is achievable and experimentally, we demonstrate
      a coupling efficiency of 99 % in the 1550 nm band. Based on the coupling scheme,
      we also show excitation of a slot mode in a slotted ring resonator and verified
      the excitation through the thermo-optic response of the rings. We show a nearly
      athermal behaviour of a PMMA filled slot ring with a thermo-optic response of
      12.8 pm/ degrees C compare to 43.5 pm/ degrees C for an air clad slot waveguide.

PMID- 29328321
TI  - Anti-waveguiding vertical-cavity surface-emitting laser at 850 nm: From concept
      to advances in high-speed data transmission.
AB  - Oxide-confined vertical cavity surface emitting lasers (VCSELs) with anti
      waveguiding AlAs-rich core presently attract a lot of attention. Anti-waveguiding
      cavity enables the maximum possible optical confinement of the VCSEL mode
      ("lambda/2 design"), increases its oscillator strength and reduces dramatically
      the optical power accumulated in the VCSEL mesa regions outside the aperture.
      VCSEL designs are suggested that favor single transverse mode operation. Modeling
      including current-induced and absorption-induced overheating shows that the
      preference for the transverse fundamental mode persists up to 10 mA current at 5
      um aperture diameter. Error-free data transmission is realized up to 160 Gb/s in
      digital-multitone (DMT) format using single-mode anti-waveguiding VCSELs. The
      approach to single-mode anti-waveguiding VCSELs is extended over a broad spectral
      range realizing error-free high-speed data transmission at both 850 nm and 910
      nm.

PMID- 29328322
TI  - Anti-dispersion phase-tunable microwave mixer based on a dual-drive dual-parallel
      Mach-Zehnder modulator.
AB  - An optically-controlled phase-tunable microwave mixer based on a dual-drive dual
      parallel Mach-Zehnder modulator (DDDP-MZM) is proposed, which supports wideband
      phase shift and immunity to power fading caused by chromatic dispersion. By using
      carrier-suppressed single side-band (CS-SSB) modulation for the local oscillator
      (LO) signal and carrier-suppressed double side-band (CS-DSB) modulation for the
      input signal, no vector superposition for the same output microwave frequency
      occurs, making the system immune from power fading caused by chromatic
      dispersion. Phase tuning is achieved by shifting the phase of the LO signal, and
      direct electrical tuning of the wideband microwave input signal is avoided, thus
      supporting large working bandwidth. A phase-shifted down-conversion experiment is
      carried out, where a phase shift with 0 ~390 degrees  and down-conversion are
      achieved with a phase variation of less than 5 degrees  and power variation less
      than 3.5 dBm when the input signal sweeps between 12 ~16 GHz. The mixer is simple
      and power-efficient since it uses a single compact modulator, and does not
      require any optical filters. No power notches are observed in the output
      microwave spectrum, proving that the dispersion-related frequency-selective
      fading is mitigated.

PMID- 29328323
TI  - Long-range distributed optical fiber hot-wire anemometer based on chirped-pulse
      PhiOTDR.
AB  - We demonstrate a technique allowing to develop a fully distributed optical fiber
      hot-wire anemometer capable of reaching a wind speed uncertainty of ~ +/-0.15m/s
      (+/-0.54km/h) at only 60 mW/m of dissipated power in the sensing fiber, and
      within only four minutes of measurement time. This corresponds to similar
      uncertainty values than previous papers on distributed optical fiber anemometry
      but requires two orders of magnitude smaller dissipated power and covers at least
      one order of magnitude longer distance. This breakthrough is possible thanks to
      the extreme temperature sensitivity and single-shot performance of chirped-pulse
      phase-sensitive optical time domain reflectometry (PhiOTDR), together with the
      availability of metal-coated fibers. To achieve these results, a modulated
      current is fed through the metal coating of the fiber, causing a modulated
      temperature variation of the fiber core due to Joule effect. The amplitude of
      this temperature modulation is strongly dependent on the wind speed at which the
      fiber is subject. Continuous monitoring of the temperature modulation along the
      fiber allows to determine the wind speed with singular low power injection
      requirements. Moreover, this procedure makes the system immune to temperature
      drifts of the fiber, potentially allowing for a simple field deployment. Being a
      much less power-hungry scheme, this method also allows for monitoring over much
      longer distances, in the orders of 10s of km. We expect that this system can have
      application in dynamic line rating and lateral wind monitoring in railway
      catenary wires.

PMID- 29328324
TI  - Temperature-insensitive optical fiber strain sensor with ultra-low detection
      limit based on capillary-taper temperature compensation structure.
AB  - An optical fiber strain sensor based on capillary-taper compensation structure
      was proposed. The theoretical simulation by using the finite element analysis
      method shows a matching condition between the capillary length and the
      interference-cavity length to achieve the zero temperature crosstalk. Meanwhile,
      the strain sensitivity can also be improved greatly at the matching condition. We
      then set up an insertion controller system with high accuracy to make sure the
      interference-cavity length can match the capillary length. Finally the fiber
      strain sensor with both ultra-low temperature-crosstalk (0.05 pm/ degrees C) and
      ultra-high sensitivity (214.35 pm/MUepsilon) was achieved, and the experimental
      results agreed well with the calculated results. The "ladder-mode" and
      repeatability experiments showed that the proposed sensor was actually with the
      ultra-low detection limit of 0.047 uE.

PMID- 29328325
TI  - Comparing laser induced plasmas formed in diode and excimer pumped alkali lasers.
AB  - Lasing on the D1 transition (62P1/2 -> 62S1/2) of cesium can be reached in both
      diode and excimer pumped alkali lasers. The first uses D2 transition (62S1/2 ->
      62P3/2) for pumping, whereas the second is pumped by photoexcitation of ground
      state Cs-Ar collisional pairs and subsequent dissociation of diatomic,
      electronically-excited CsAr molecules (excimers). Despite lasing on the same D1
      transition, differences in pumping schemes enables chemical pathways and
      characteristic timescales unique for each system. We investigate unavoidable
      plasma formation during operation of both systems side by side in Ar/C2H6/Cs.

PMID- 29328326
TI  - Quadrupole mode plasmon resonance enabled subwavelength metal-dielectric grating
      optical reflection filters.
AB  - A metal-dielectric subwavelength grating structure was investigated for making
      single-peak narrow linewidth optical reflection filters in the near-infrared
      region. The subwavelength grating filter structure consists of a one-dimensional
      periodic array of metal (gold) and dielectric (Al2O3) elements on a dielectric
      substrate. Optimized reflection filters have a single reflection peak with ~10 nm
      linewidth in the infrared region over a wide spectral band. Finite-difference
      time-domain (FDTD) simulations and multipole analysis show that the narrow
      linewidth reflection is due to the coupling of the Rayleigh anomaly wave to the
      quadrupole plasmon resonance mode of the subwavelength metal-dielectric grating.
      Additionally, it was found that the contrast of the indices of refraction of two
      dielectric materials in the subwavelength structure is critical for realizing
      optical filter effect.

PMID- 29328327
TI  - Realizable design of field taper via coordinate transformation.
AB  - Complex electromagnetic structures can be designed by exploiting the concept of
      spatial coordinate transformations. In this paper, we define a coordinate
      transformation scheme that enables one to taper the electric field between two
      waveguides of different cross-sections. The electromagnetic field launched from
      the wide input waveguide is compressed in the proposed field tapering device and
      guided into the narrow output waveguide. In closed rectangular waveguide
      configurations, the taper can further play the role of a mode selector due to the
      output waveguide's cut-off frequency. Realizable permittivity and permeability
      values that can be achieved with common existing metamaterials are determined
      from the transformation equations and simplified by a proposed parameter
      reduction method. Both a 2D continuous design model and a potential 3D
      discretized realization model are presented at microwave frequencies and the
      performances of the tapering devices are verified by full-wave finite element
      numerical simulations. Finally, near-field distributions are shown to demonstrate
      the field tapering functionality.

PMID- 29328328
TI  - Broadband integrated polarization rotator using three-layer metallic grating
      structures.
AB  - In this work, we demonstrate broadband integrated polarization rotator (IPR) with
      a series of three-layer rotating metallic grating structures. This transmissive
      optical IPR can conveniently rotate the polarization of linearly polarized light
      to any desired directions at different spatial locations with high conversion
      efficiency, which is nearly constant for different rotation angles. The linear
      polarization rotation originates from multi-wave interference in the three-layer
      grating structure. We anticipate that this type of IPR will find wide
      applications in analytical chemistry, biology, communication technology, imaging,
      etc.

PMID- 29328329
TI  - Speeding up Raman spectral imaging by the three-dimensional low rank estimation
      method.
AB  - Raman spectral imaging has been widely used as a very important analytical tool
      in various fields. For obtaining the high spectral signal-to-noise ratio Raman
      images, the long integration time is necessary, which is placing a limit on the
      application of Raman spectral imaging. We introduce a simple and feasible
      numerical method of the Three-dimensional Low Rank Estimation (3D-LRE), which can
      speed up the data acquisition process of the Raman spectral imaging. The spectral
      signal-to-noise ratio of the Raman images can be increased by over 75 times and
      the speed of the data acquisition can be improved by over 30 times. By combining
      with line-scan or multifocus-scan techniques, the Raman images can be obtained in
      a few seconds.

PMID- 29328330
TI  - Evaluation of thermal expansion coefficient of carbon fiber reinforced composites
      using electronic speckle interferometry.
AB  - An optical system for measuring the coefficient of thermal expansion (CTE) of
      materials has been developed based on electronic speckle interferometry. In this
      system, the temperature can be varied from -60 degrees C to 180 degrees C with a
      Peltier device. A specific specimen geometry and an optical arrangement based on
      the Michelson interferometer are proposed to measure the deformation along two
      orthogonal axes due to temperature changes. The advantages of the system include
      its high sensitivity and stability over the whole range of measurement. The
      experimental setup and approach for estimating the CTE was validated using an
      Aluminum alloy. Following this validation, the system was applied for
      characterizing the CTE of carbon fiber reinforced composite (CFRP) laminates. For
      the unidirectional fiber reinforced composites, the CTE varied with fiber
      orientation and exhibits anisotropic behavior. By stacking the plies with
      specific angles and order, the CTE of a specific CFRP was constrained to a low
      level with minimum variation temperature. The optical system developed in this
      study can be applied to CTE measurement for engineering and natural materials
      with high accuracy.

PMID- 29328331
TI  - Directional torsion and temperature discrimination based on a multicore fiber
      with a helical structure.
AB  - We propose and experimentally demonstrate a directional torsion sensor based on a
      Mach-Zehnder interferometer formed in a multicore fiber (MCF) with a ~570-MUm
      long helical structure (HS). The HS was fabricated into the MCF by simply pre
      twisting and then heating with a CO2 laser splicing system. This device shows the
      capability of directional torsion measurement from -17.094 rad/m to 15.669 rad/m
      with the sensitivity of ~0.118 nm/(rad/m). Moreover, since the multiple
      interferences respond differently to torsion and temperature simultaneously, the
      temperature cross-sensitivity of the proposed sensor can be eliminated
      effectively. Besides, the sensor owns other merits such as easy fabrication and
      good mechanical robustness.

PMID- 29328332
TI  - Wavelength tuning of surface plasmon coupled quantum well infrared
      photodetectors.
AB  - A novel method of detection wavelength tuning for surface plasmon coupled quantum
      well infrared photodetectors (QWIPs) was demonstrated. By changing of the
      thickness of the top contact layer, the detection wavelength can be adjusted. The
      displacement of the detection wavelength is related to the effective dielectric
      constant of the dielectric layers in the device structure. The peak wavelength
      moves toward longer wavelength as the contact layer thickness decreases. With a
      proper match of the 2D metal hole array and the QW absorption region, the
      responsivity can be kept within a reasonable range for samples with different top
      contact layer thicknesses.

PMID- 29328333
TI  - Broadband tunable filter based on the loop of multimode Bragg grating.
AB  - A broadband tunable silicon filter has been demonstrated on silicon-on-insulator
      platform. The device is based on the loop of multimode anti-symmetric waveguide
      Bragg grating. A wide bandwidth tunability about 1.455 THz (0.117-1.572 THz) is
      achieved. The device, functions like a ring, can realize the bandwidth tunable of
      the drop port and the through port. And, its feature has simultaneous wavelength
      tuning and no free space ranges limitation. A high out-of-band contrast of 30 dB
      is achieved with a bandwidth of 1.572 THz (Deltalambda = 13 nm). The out-of-band
      contrast is 18 dB at the minimum bandwidth 0.117 THz (Deltalambda = 1.0 nm).

PMID- 29328334
TI  - Computation and analysis of backward ray-tracing in aero-optics flow fields.
AB  - A backward ray-tracing method is proposed for aero-optics simulation. Different
      from forward tracing, the backward tracing direction is from the internal sensor
      to the distant target. Along this direction, the tracing in turn goes through the
      internal gas region, the aero-optics flow field, and the freestream. The
      coordinate value, the density, and the refractive index are calculated at each
      tracing step. A stopping criterion is developed to ensure the tracing stops at
      the outer edge of the aero-optics flow field. As a demonstration, the analysis is
      carried out for a typical blunt nosed vehicle. The backward tracing method and
      stopping criterion greatly simplify the ray-tracing computations in the aero
      optics flow field, and they can be extended to our active laser illumination aero
      optics study because of the reciprocity principle.

PMID- 29328335
TI  - Optical frequency combs based on a period-doubling mode-locked Er-doped fiber
      laser.
AB  - The phase-locking mechanism and results of a frequency comb based on a period
      doubling mode-locked (PD-ML) fiber laser were investigated. A mode-locked fiber
      laser was designed to switch from fundamental mode locking (FML) to PD-ML with
      similar output pulses by simply changing the pump. Experimental results show that
      the new comb teeth generated in the PD-ML are strongly correlated with the
      original teeth and have a consistent carrier-envelope offset (CEO) frequency.
      Controlling the pump and cavity length is also suited for phase-locking the PD-ML
      laser. With the same f-to-2f heterodyne beat system and locking circuit, phase
      locking of both PD-ML and FML-based optical combs with two repetition rates, and
      switching between them, were obtained by changing the pump only.

PMID- 29328336
TI  - Quantitative phase microscopy for cellular dynamics based on transport of
      intensity equation.
AB  - We demonstrate a simple method for quantitative phase imaging of tiny transparent
      objects such as living cells based on the transport of intensity equation. The
      experiments are performed using an inverted bright field microscope upgraded with
      a flipping imaging module, which enables to simultaneously create two laterally
      separated images with unequal defocus distances. This add-on module does not
      include any lenses or gratings and is cost-effective and easy-to-alignment. The
      validity of this method is confirmed by the measurement of microlens array and
      human osteoblastic cells in culture, indicating its potential in the applications
      of dynamically measuring living cells and other transparent specimens in a
      quantitative, non-invasive and label-free manner.

PMID- 29328337
TI  - Development and validation of a simulation method, PeCHREM, for evaluating spatio
      temporal concentration changes of paddy herbicides in rivers.
AB  - In pesticide risk management in Japan, predicted environmental concentrations are
      estimated by a tiered approach, and the Ministry of the Environment also performs
      field surveys to confirm the maximum concentrations of pesticides with risk
      concerns. To contribute to more efficient and effective field surveys, we
      developed the Pesticide Chemicals High Resolution Estimation Method (PeCHREM) for
      estimating spatially and temporally variable emissions of various paddy
      herbicides from paddy fields to the environment. We used PeCHREM and the G-CIEMS
      multimedia environmental fate model to predict day-to-day environmental
      concentration changes of 25 herbicides throughout Japan. To validate the
      PeCHREM/G-CIEMS model, we also conducted a field survey, in which river waters
      were sampled at least once every two weeks at seven sites in six prefectures from
      April to July 2009. In 20 of 139 sampling site-herbicide combinations in which
      herbicides were detected in at least three samples, all observed concentrations
      differed from the corresponding prediction by less than one order of magnitude.
      We also compared peak concentrations and the dates on which the concentrations
      reached peak values (peak dates) between predictions and observations. The peak
      concentration differences between predictions and observations were less than one
      order of magnitude in 66% of the 166 sampling site-herbicide combinations in
      which herbicide was detected in river water. The observed and predicted peak
      dates differed by less than two weeks in 79% of these 166 combinations. These
      results confirm that the PeCHREM/G-CIEMS model can improve the efficiency and
      effectiveness of surveys by predicting the peak concentrations and peak dates of
      various herbicides.

PMID- 29328338
TI  - Binding affinity prediction of nanobody-protein complexes by scoring of molecular
      dynamics trajectories.
AB  - Nanobodies offer a viable alternative to antibodies for engineering high affinity
      binders. Their small size has an additional advantage: it allows exploiting
      computational protocols for optimizing their biophysical features, such as the
      binding affinity. The efficient prediction of this quantity is still considered a
      daunting task especially for modelled complexes. We show how molecular dynamics
      can successfully assist in the binding affinity prediction of modelled nanobody
      protein complexes. The approximate initial configurations obtained by in silico
      design must undergo large rearrangements before achieving a stable conformation,
      in which the binding affinity can be meaningfully estimated. The scoring
      functions developed for the affinity evaluation of crystal structures will
      provide accurate estimates for modelled binding complexes if the scores are
      averaged over long finite temperature molecular dynamics simulations.

PMID- 29328339
TI  - Reduced sintering of mass-selected Au clusters on SiO2 by alloying with Ti: an
      aberration-corrected STEM and computational study.
AB  - Au nanoparticles represent the most remarkable example of a size effect in
      heterogeneous catalysis. However, a major issue hindering the use of Au
      nanoparticles in technological applications is their rapid sintering. We explore
      the potential of stabilizing Au nanoclusters on SiO2 by alloying them with a
      reactive metal, Ti. Mass-selected Au/Ti clusters (400 000 amu) and Au2057
      clusters (405 229 amu) were produced with a magnetron sputtering, gas
      condensation cluster beam source in conjunction with a lateral time-of-flight
      mass filter, deposited onto a silica support and characterised by XPS and LEIS.
      The sintering dynamics of mass-selected Au and Au/Ti alloy nanoclusters were
      investigated in real space and real time with atomic resolution aberration
      corrected HAADF-STEM imaging, supported by model DFT calculations. A strong
      anchoring effect was revealed in the case of the Au/Ti clusters, because of a
      much increased local interaction with the support (by a factor 5 in the
      simulations), which strongly inhibits sintering, especially when the clusters are
      more than ~0.60 nm apart. Heating the clusters at 100  degrees C for 1 h in a
      mixture of O2 and CO, to simulate CO oxidation conditions, led to some
      segregation in the Au/Ti clusters, but in line with the model computational
      investigation, Au atoms were still present on the surface. Thus size-selected,
      deposited nanoalloy Au/Ti clusters appear to be promising candidates for
      sustainable gold-based nanocatalysis.

PMID- 29328340
TI  - Interactions between brush-grafted nanoparticles within chemically identical
      homopolymers: the effect of brush polydispersity.
AB  - We systematically examined the polymer-mediated interparticle interactions
      between polymer-grafted nanoparticles (NPs) within chemically identical
      homopolymer matrices through experimental and computational efforts. In
      experiments, we prepared thermally stable gold NPs grafted with polystyrene (PS)
      or poly(methyl methacrylate) (PMMA), and they were mixed with corresponding
      homopolymers. The nanocomposites are well dispersed when the molecular weight
      ratio of free to grafted polymers, alpha, is small. For alpha above 10, NPs are
      partially aggregated or clumped within the polymer matrix. Such aggregation of
      NPs at large alpha has been understood as an autophobic dewetting behavior of
      free homopolymers on brushes. In order to theoretically investigate this
      phenomenon, we calculated two particle interaction using self-consistent field
      theory (SCFT) with our newly developed numerical scheme, adopting two-dimensional
      finite volume method (FVM) and multi-coordinate-system (MCS) scheme which makes
      use of the reflection symmetry between the two NPs. By calculating the polymer
      density profile and interparticle potential, we identified the effects of several
      parameters such as brush thickness, particle radius, alpha, brush chain
      polydispersity, and chain end mobility. It was found that increasing alpha is the
      most efficient method for promoting autophobic dewetting phenomenon, and the
      attraction keeps increasing up to alpha = 20. At small alpha values, high
      polydispersity in brush may completely nullify the autophobic dewetting, while at
      intermediate alpha values, its effect is still significant in that the
      interparticle attractions are heavily reduced. Our calculation also revealed that
      the grafting type is not a significant factor affecting the NP aggregation
      behavior. The simulation result qualitatively agrees with the
      dispersion/aggregation transition of NPs found in our experiments.

PMID- 29328344
TI  - Kinetics of thermal cis-trans isomerization in a phototropic azobenzene-based
      single-component liquid crystal in its nematic and isotropic phases.
AB  - Single-component azobenzene-based phototropic liquid crystals (PtLC) are
      promising materials that have started to be explored for photonic applications.
      One of the essential factors determining the applicability of these materials is
      the rate of the thermally driven cis-trans isomerization. In this paper, the
      kinetics of the thermal back cis-to-trans reaction in a pure 4-hexyl-4'
      methoxyazobenzene (6-AB-O1) compound in its isotropic liquid and nematic phases
      is studied (the undoped LC). The reaction rate constants, activation energies and
      thermal activation parameters were determined based on spectroscopic studies. The
      reaction kinetics is compared to that measured for the compound dissolved in
      chloroform. The results demonstrate that the thermal back reaction depends on the
      phase and molecular environment of the cis-isomer. Moreover, the effect of
      temperature on the absorption spectra of 6-AB-O1 in its isotropic, nematic and
      crystalline phases is examined. The changes in the compound's absorption spectra
      in the respective phases have been correlated to the positional order parameter
      S.

PMID- 29328343
TI  - In situ fluorescence activation of DNA-silver nanoclusters as a label-free and
      general strategy for cell nucleus imaging.
AB  - A facile, general and turn-on nucleus imaging strategy was first developed based
      on in situ fluorescence activation of C-rich dark silver nanoclusters by G-rich
      telomeres. After a simple incubation without washing, nanoclusters could
      selectively stain the nucleus with intense red luminescence, which was confirmed
      using fixed/living cells and several cell lines.

PMID- 29328345
TI  - Oxidative radical divergent Si-incorporation: facile access to Si-containing
      heterocycles.
AB  - A copper-catalyzed oxidative radical strategy to avoid the use of the highly
      expensive noble metal/ligand catalytic systems is described, which allows
      selective activation of dual chemical bonds around the Si-atom center relying on
      the nature of alkylsilanes. While for tertiary silanes selective
      functionalization of Si-H/silyl C(sp3)-H bonds in intermolecular oxidative
      annulation cascades with N-(2-(ethynyl)aryl)acrylamides toward silino[3,4
      c]quinolin-5(3H)-ones, when using secondary silanes and HSi(TMS)3, dual Si-H
      bonds or Si-H/Si-Si bonds are selectively cleaved leading to 4H-silolo[3,4
      c]quinolin-4-ones.

PMID- 29328346
TI  - 1,4-Additions of tricyclic 1,4-diphosphinines - a novel system to study sigma
      bond activation and pi-pi dispersion interactions.
AB  - The dienic nature of the aromatic pi-system in 1,4-diphosphinines remains largely
      unexplored to this day due to a lack of facile and efficient synthetic protocols.
      Recently reported stable, tricyclic 1,4-diphosphinines were used to explore the
      thermal reactivity of the pi-system towards an array of dienophiles in [4pi+2pi]-
      and, for the first time, in [4pi+2sigma]-type cycloaddition reactions.

PMID- 29328347
TI  - As tall as my peers - similarity in body height between migrants and hosts.
AB  - ABSTRACT: Background: We define migrants as people who move from their place of
      birth to a new place of residence. Migration usually is directed by "Push-Pull"
      factors, for example to escape from poor living conditions or to find more
      prosperous socio-economic conditions. Migrant children tend to assimilate
      quickly, and soon perceive themselves as peers within their new social networks.
      Differences exist between growth of first generation and second generation
      migrants. Methods: We review body heights and height distributions of historic
      and modern migrant populations to test two hypotheses: 1) that migrant and
      adopted children coming from lower social status localities to higher status
      localities adjust their height growth toward the mean of the dominant recipient
      social network, and 2) social dominant colonial and military migrants display
      growth that significantly surpasses the median height of both the conquered
      population and the population of origin. Our analytical framework also considered
      social networks. Recent publications indicate that spatial connectedness
      (community effects) and social competitiveness can affect human growth. Results:
      Migrant children and adolescents of lower social status rapidly adjust in height
      towards average height of their hosts, but tend to mature earlier, and are prone
      to overweight. The mean height of colonial/military migrants does surpass that of
      the conquered and origin population. Conclusion: Observations on human social
      networks, non-human animal strategic growth adjustments, and competitive growth
      processes strengthen the concept of social connectedness being involved in the
      regulation of human migrant growth.

PMID- 29328348
TI  - Body image issues in Lithuanian females before and during pregnancy.
AB  - ABSTRACT: There is a risk that during pregnancy a woman's changing physique might
      result in stronger concerns about her appearance and may lead to negative
      consequences both for mother and foetus. The aim of the present study was to
      assess women's self-esteem, body image and weight control before and during
      pregnancy. A cross-sectional study was carried out at the Centre of Obstetrics
      and Gynaecology of Vilnius University Hospital. In total, 234 pregnant women were
      investigated. The Self-esteem was measured by Rosenberg's scale (1965), while the
      attitude towards the body size - by Stunkard's figure rating scale (1983). When
      rating their actual body size and the preferred body shape using Stunkard's
      figures, the investigated females chose, on average, 3.40 and 2.93 (respectively)
      size figures for the period before pregnancy (p < 0.05), while they picked 4.38
      and 3.44 (respectively) figures during pregnancy (p < 0.05). Women's efforts not
      to gain weight during pregnancy were not determined by their opinion of their
      body size during pregnancy (rs(232) = 0.136,p > 0.05). Regardless of their body
      shape assessment during pregnancy, pregnant women did not restrict their diet
      (rs(232) = 0.064,p > 0.05). Conclusions: during pregnancy women assessed their
      weight gain adequately, pregnant women chose larger body sizes as an ideal
      physique if compared to the ones of the period before pregnancy, women's efforts
      not to gain weight during pregnancy were not determined by their body size
      perception during pregnancy, pregnant women, despite their body shape assessment
      during pregnancy, did not restrict their diet, i.e. pregnant women became
      psychologically adapted to their body changes during pregnancy, and the maternity
      became a much more important factor than the beauty ideals associated with
      slender figures.

PMID- 29328349
TI  - Sexual dimorphism in physical education students of equal body height.
AB  - ABSTRACT: The aim: This paper's aim is to assess the level of development and
      size of particular body parts and dimorphic differences with regard to body
      height. Methods: The research was carried out over the period of 1995-2010 on a
      1,969-strong cohort of first-year students of physical education, aged 19-21. The
      following somatic features were measured: body height and weight, breadth of
      distal femoral epiphysis, breadth of distal brachial epiphysis, four skinfolds,
      arm circumference, and calf circumference. Using the results, the shares of
      endomorphy, mesomorphy, and ectomorphy were calculated as well as the mean values
      of particular features and their supplemental values and regression equations.
      Results: With regard to height, the women students exhibit higher share of
      endomorphy than do the men students who, in turn, are characterised by a higher
      share of mesomorphy, the differences being statistically significant. The women
      also exhibit a higher share of ectomorphy, with differences statistically
      significant. The regression equation shows that the share of endomorphy decreases
      with height in the case of both sexes. Conclusions: The men students' body build
      is dominated by mesomorphy and endomorphy, while the women students' - by
      endomorphy. Sexual dimorphism is best seen in the mesomorphic build.

PMID- 29328352
TI  - New Drugs & Indications for 2017: The Year in Review.

PMID- 29328350
TI  - Helicobacter pylori DNA obtained from the stomach specimens of two 17th century
      Korean mummies.
AB  - ABSTRACT: Helicobacter pylori is a bacterium that grows in the stomach mucosal
      epithelium, and can induce gastric diseases. Although many studies on modern H.
      pylori genomes have been reported from all over the world, a comprehensive
      picture of H. pylori is still lacking. Therefore, there is a pressing need to
      obtain archaeological specimens and to subject the ancient DNA (aDNA) extracted
      therefrom to analysis. Considering the typically excellent state of preservation
      of Joseon mummies discovered in Korea, we thus tried to isolate ancient H. pylori
      DNA from their mummified stomach specimens. After screening Korean mummy stomachs
      containing remnant H. pylori DNA, vacA (s- and m-region) alleles were
      successfully identified in the stomach isolates of two samples. The H. pylori
      strains identified had vacA s1/m2 (Cheongdo mummy) and s1 (Dangjin mummy)
      alleles. This paper is significant in that it is the first report of presumptive
      ancient H. pylori DNA obtained from East Asian archaeological specimens. However,
      full characterization and exploitation of ancient H. pylori DNA remnant in Joseon
      mummy specimens will require subsequent investigations utilizing the most cutting
      edge techniques established for the analysis of ancient intestinal-content
      samples, such as next-generation sequencing (NGS).

PMID- 29328351
TI  - Mindful Self-Compassion: How it Can Enhance Resilience.

PMID- 29328353
TI  - 2017 Reviewers.

PMID- 29328354
TI  - End-of-Life Conversations as a Legacy.
AB  - Advance directives such as living wills and health care powers of attorney are
      important documents that offer patients ways to avoid unwanted care when they are
      unable to express their wishes. Although health care professionals have increased
      focus on advance care planning in recent years, approximately two thirds of
      American adults do not have advance medical directives. In addition, 90% of
      individuals believe that talking to loved ones about end-of-life wishes is
      important, but only 27% have done so. It is important for nurses to understand
      the complex factors that influence how individuals make health care decisions and
      identify ways to encourage conversations with family, friends, and health care
      providers to help clarify patients' wishes for endof-life care. [Journal of
      Psychosocial Nursing and Mental Health Services, 56(1), 32-35.].

PMID- 29328355
TI  - Untitled by Veronica Benning.

PMID- 29328356
TI  - Factor Structure of the Eating Disorder Examination-Questionnaire in a Clinical
      Sample of Adult Women With Anorexia Nervosa.
AB  - An exploratory factor analysis on the Eating Disorder Examination-Questionnaire
      (EDE-Q) is presented for a clinical sample of women with anorexia nervosa. THE
      EDE-Q was completed by 169 participants after admission to an inpatient unit for
      eating disorders. Results of the current study did not support the four-factor
      model presented by the EDE-Q. A new four-factor solution was obtained with two
      factors showing similarity to the Restraint and Eating Concern subscales of the
      original model. The Shape and Weight Concern items primarily loaded together on
      one factor, along with preoccupation with food and fear of losing control over
      eating, two Eating Concern items. Finally, an appearance factor was obtained that
      supports the results of prior research. [Journal of Psychosocial Nursing and
      Mental Health Services, 56(5), 33-39.].

PMID- 29328357
TI  - Sensitizing Inpatient Mental Health Staff to the Challenges of Aging.
AB  - Although the aging inpatient population in state psychiatric hospitals is growing
      significantly, there are few examples of available training to improve staff
      knowledge and practice. The current article describes a 10-week training series
      developed through a university and psychiatric hospital collaboration. Training
      was attended by 135 direct care nursing and rehabilitation staff and focused on
      improving aging awareness, problem solving, using person-centered therapeutic
      techniques, and engaging older adults. Staff reported improvements in therapeutic
      techniques, knowledge, concrete strategies for providing care, and stress
      management skills. Specialized training to improve understanding of aging
      processes and communication with older adults may also improve inpatient staff
      knowledge and skills. As the aging inpatient population in state psychiatric
      hospitals continues to grow, future work should develop manualized training
      initiatives to address communication needs of older adults and intervention
      strategies that can be used by mental health nursing staff when working with this
      population. [Journal of Psychosocial Nursing and Mental Health Services, 56(4),
      12-16.].

PMID- 29328358
TI  - Team Development Measure in Interprofessional Graduate Education: A Pilot Study.
AB  - A faculty team developed the 4-week Recovery-Based Interprofessional Distance
      Education (RIDE) rotation for graduate students in their disciplines. The
      evaluation team identified the Team Development Measure (TDM) as a potential
      alternative to reflect team development during the RIDE rotation. The TDM,
      completed anonymously online, was piloted on the second student cohort (N = 18)
      to complete the RIDE rotation. The overall pretest mean was 60.73 points (SD =
      11.85) of a possible 100 points, indicating that students anticipated their RIDE
      team would function at a moderately high level during the 4-week rotation. The
      overall posttest mean, indicating student perceptions of actual team functioning,
      was 72.71 points (SD = 23.31), an average increase of 11.98 points. Although not
      statistically significant, Cohen's effect size (d = 0.43) indicates an observed
      difference of large magnitude. No other published work has used the TDM as a pre
      /posttest measure of team development. The authors believe the TDM has several
      advantages as a measure of student response to interprofessional education
      offerings, particularly in graduate students with prior experience on health care
      teams. Further work is needed to validate and extend the findings of this pilot
      study. [Journal of Psychosocial Nursing and Mental Health Services, 56(4), 18
      22.].

PMID- 29328359
TI  - Destigmatizing Mental Illness: An Innovative Evidence-Based Undergraduate
      Curriculum.
AB  - Stigma toward individuals with mental illness is prevalent, not only in society
      but also among nurses caring for this population. Such stigma contributes to
      health disparities, discrimination, and a lack of providers working with those
      who experience mental illness. An evidence-based anti-stigma curriculum
      innovation in a mental health nursing course in an undergraduate program is
      described. The curriculum change, undertaken over 2 years, included two elements:
      (a) contact-based education, and (b) reflective activities. For the contact-based
      education element, volunteers with varying mental illnesses modeling a recovery
      focus spoke with students and reinforced the content of that day's lecture. For
      the reflective element, students engaged in reflective activities regarding
      stigma, personal biases, and changed perceptions at three points: before, during,
      and after the contact-based education series. Implications related to nursing and
      nursing education are presented. [Journal of Psychosocial Nursing and Mental
      Health Services, 56(5), 50-55.].

PMID- 29328360
TI  - Metabolic Side Effects in Patients Using Atypical Antipsychotic Medications
      During Hospitalization.
AB  - The current research evaluated metabolic side effects in inpatients (N = 271)
      using atypical antipsychotic medications in a psychiatric hospital in Turkey
      between June and December 2016. Data were collected via an information form
      created after reviewing the literature at the time of patients' hospitalization
      and discharge. According to the analysis, 73.8% of patients stated they
      experienced side effects from antipsychotic medications and 20.7% of patients
      experienced weight gain. A statistical difference was detected among body mass
      index, waist circumference, diastolic blood pressure, and heart rate during
      patient hospitalization and discharge. Patients using atypical anti-psychotic
      medications gained weight, had increased cardiovascular risk, and experienced
      adverse effects on their physical health during hospitalization. Mental health
      nurses should inform patients of medication effects and possible side effects,
      monitor side effects, and teach patients how to manage metabolic side effects.
      [Journal of Psychosocial Nursing and Mental Health Services, 56(4), 28-37.].

PMID- 29328361
TI  - Logistic regression analysis for the identification of the metastasis-associated
      signaling pathways of osteosarcoma.
AB  - Osteosarcoma (OS) is the most common histological type of primary bone cancer.
      The present study was designed to identify the key genes and signaling pathways
      involved in the metastasis of OS. Microarray data of GSE39055 were downloaded
      from the Gene Expression Omnibus database, which included 19 OS biopsy specimens
      before metastasis (control group) and 18 OS biopsy specimens after metastasis
      (case group). After the differentially expressed genes (DEGs) were identified
      using the Linear Models for Microarray Analysis package, hierarchical clustering
      analysis and unsupervised clustering analysis were performed separately, using
      orange software and the self-organization map method. Based upon the Database for
      Annotation, Visualization and Integrated Discovery tool and Cytoscape software,
      enrichment analysis and protein-protein interaction (PPI) network analysis were
      conducted, respectively. After function deviation scores were calculated for the
      significantly enriched terms, hierarchical clustering analysis was performed
      using Cluster 3.0 software. Furthermore, logistic regression analysis was used to
      identify the terms that were significantly different. Those terms that were
      significantly different were validated using other independent datasets. There
      were 840 DEGs in the case group. There were various interactions in the PPI
      network [including intercellular adhesion molecule-1 (ICAM1), transforming growth
      factor beta1 (TGFB1), TGFB1-platelet-derived growth factor subunit B (PDGFB) and
      PDGFB-platelet-derived growth factor receptor-beta (PDGFRB)]. Regulation of cell
      migration, nucleotide excision repair, the Wnt signaling pathway and cell
      migration were identified as the terms that were significantly different. ICAM1,
      PDGFB, PDGFRB and TGFB1 were identified to be enriched in cell migration and
      regulation of cell migration. Nucleotide excision repair and the Wnt signaling
      pathway were the metastasis-associated pathways of OS. In addition, ICAM1, PDGFB,
      PDGFRB and TGFB1, which were involved in cell migration and regulation of cell
      migration may affect the metastasis of OS.

PMID- 29328362
TI  - MicroRNA-493-5p promotes apoptosis and suppresses proliferation and invasion in
      liver cancer cells by targeting VAMP2.
AB  - The aim of the present study was to explore the role of miR-493-5p in liver
      cancer tissues and cell lines, and its effect on cell behavioral characteristics.
      The expression of miR-493-5p was detected by reverse transcription-quantitative
      polymerase chain reaction (RT-qPCR) in liver cancer tissues and cell lines
      (hepatic cell line HL-7702 and the liver cancer cell lines HCCC-9810, HuH-7 and
      HepG2). In addition, the mechanism by which miR-493-5p mediates its effects was
      analyzed via the transfection of miR-493-5p mimic and negative control miRNA into
      HepG2 cells. The viability, proliferation, apoptosis and invasion of the cells
      were analyzed using MTT assay, flow cytometry and Transwell chamber experiments.
      Furthermore, the effect of miR-493-5p on the expression of vesicle associated
      membrane protein 2 (VAMP2) was assayed using a dual-luciferase reporter system,
      and VAMP2 protein levels were determined by western blot analysis. In addition,
      following the cotransfection of HepG2 cells with pcDNA3.1-VAMP2 plasmid and miR
      493-5p mimic, the role of miR-493-5p as a regulator of VAMP2 was evaluated using
      MTT assay, flow cytometry and Transwell chamber experiments. RT-qPCR analysis
      indicated that the expression of miR-493-5p in liver cancer tissues and cell
      lines was decreased significantly compared with that in adjacent normal liver
      tissues and normal liver cell lines, respectively. Compared with the control
      group, the cells transfected with miR-493-5p mimic (the miR-493-5p overexpression
      group) exhibited reduced cell viability, a reduced percentage of cells in the S
      phase and an increased percentage of apoptotic cells. In addition, fewer cells
      passed through the Transwell membrane in the miR-493-5p overexpression group
      compared with the control group. In the dual-luciferase reporter assay,
      luciferase activity in the miR-493-5p overexpression group was attenuated
      compared with that in the control group. In addition, western blot analysis
      indicated that the VAMP2 protein levels in the miR-493-5p overexpression group
      were lower than those in the control group. Furthermore, in cells overexpressing
      miR-493-5p and VAMP2 simultaneously, the biological behavior of the cells,
      including cell viability, cell cycle and cell invasiveness, was significantly
      rescued compared with that of the control group transfected with miR-493-5p
      alone. In conclusion, miR-493-5p is indicated to be a tumor suppressor gene, and
      is downregulated in human liver cancer. miR-493-5p overexpression promotes cell
      apoptosis and inhibits the proliferation and migration of liver cancer cells by
      negatively regulating the expression of VAMP. These observations suggest the
      potential of treating liver cancer by the overexpression of microRNA-493-5p.

PMID- 29328363
TI  - Support vector machine classifier for prediction of the metastasis of colorectal
      cancer.
AB  - Colorectal cancer (CRC) is one of the most common cancers and a major cause of
      mortality. The present study aimed to identify potential biomarkers for CRC
      metastasis and uncover the mechanisms underlying the etiology of the disease. The
      five datasets GSE68468, GSE62321, GSE22834, GSE14297 and GSE6988 were utilized in
      the study, all of which contained metastatic and non-metastatic CRC samples.
      Among them, three datasets were integrated via meta-analysis to identify the
      differentially expressed genes (DEGs) between the two types of samples. A protein
      protein interaction (PPI) network was constructed for these DEGs. Candidate genes
      were then selected by the support vector machine (SVM) classifier based on the
      betweenness centrality (BC) algorithm. A CRC dataset from The Cancer Genome Atlas
      database was used to evaluate the accuracy of the SVM classifier. Pathway
      enrichment analysis was carried out for the SVM-classified gene signatures. In
      total, 358 DEGs were identified by meta-analysis. The top ten nodes in the PPI
      network with the highest BC values were selected, including cAMP responsive
      element binding protein 1 (CREB1), cullin 7 (CUL7) and signal sequence receptor 3
      (SSR3). The optimal SVM classification model was established, which was able to
      precisely distinguish between the metastatic and non-metastatic samples. Based on
      this SVM classifier, 40 signature genes were identified, which were mainly
      enriched in protein processing in endoplasmic reticulum (e.g., SSR3), AMPK
      signaling pathway (e.g., CREB1) and ubiquitin mediated proteolysis (e.g., FBXO2,
      CUL7 and UBE2D3) pathways. In conclusion, the SVM-classified genes, including
      CREB1, CUL7 and SSR3, precisely distinguished the metastatic CRC samples from the
      non-metastatic ones. These genes have the potential to be used as biomarkers for
      the prognosis of metastatic CRC.

PMID- 29328366
TI  - Expression of DNA damage response proteins in gastric cancer: Comprehensive
      protein profiling and histological analysis.
AB  - Gastric cancer is the third major cause of cancer-related mortality in Japan. The
      aim of this study was to identify a factor implicated in the biology of gastric
      cancer by comprehensive protein profiling. Protein profiling was carried out by
      liquid chromatography-tandem mass spectrometry, using formalin-fixed paraffin
      embedded specimens of 17 gastric cancer cases. Pathway analysis and orthogonal
      partial least square-discriminant analysis suggested the significant expression
      of ribonucleoproteins, heterogeneous nuclear ribonucleoproteins, interleukin
      binding factor 2 (ILF2), KU70 and KU80, which are involved in DNA damage response
      (DDR). Thus, the expression and phosphorylation levels of KU70, ILF2, CHK1 and
      CHK2 were examined by immunohistochemistry in 42 cases of gastric cancer. The
      expressions of ILF2 and CHK1 were unaffected in all cases. The expression and
      phosphorylation of CHK2 were absent in 2 cases. Despite the expression of
      proteins, the phosphorylation of KU70 and CHK2 appeared to be impaired in 1 and 4
      cases, respectively. In 7 out of 42 cases (17%), DDR appeared to be impaired.
      Recurrence was noted in 2 out of these 7 cases (29%), whereas the recurrence was
      noted in 2 out of the remaining 35 cases (6%). The expression levels of KU70,
      ILF2, CHK1, CHK2 and TP53 were further examined in 4 gastric cancer cell lines.
      The expression and phosphorylation levels following exposure to ultraviolet
      radiation were abnormal in the 3 cell lines. The normal consecutive
      phosphorylation of CHK1 and CHK2, the upregulation of TP53 and an increase in
      apoptotic cell death following exposure to ultraviolet radiation was detected
      only in one cell line, suggesting that the preserved functions of DDR and TP53
      are necessary for the determination of cell fate. It is thus suggested that DDR
      plays an important role in the pathobiology of gastric cancers.

PMID- 29328365
TI  - Nuclear GSK3beta induces DNA double-strand break repair by phosphorylating 53BP1
      in glioblastoma.
AB  - Glioblastoma is the most malignant and lethal subtype brain tumors with high risk
      of recurrence and therapeutic resistance. Emerging evidence has indicated that
      glycogen synthesis kinase 3 (GSK3)beta plays oncogenic roles in multiple tumor
      types; however, the underlying mechanisms remain largely unknown. It has also
      been demonstrated that p53 binding protein 1 (53BP1) plays a central role in DNA
      double-strand break (DSB) repair. This study aimed to reveal the significance of
      GSK3beta translocation from the cytoplasm to the nucleus, and to determine
      whether GSK3beta induces DNA DSB repair in the nuclei of glioblastoma cells via
      phospho-53BP1. By performing in vitro experiments, we found that GSK3beta
      translocated from the cytoplasm to the nucleus, and it then bound to 53BP1
      following exposure to IR (IR). In addition, 53BP1-mediated DNA DSB repair was
      observed to be abrogated by the inhibition of GSK3beta. Further experiments on
      the phosphorylation site of 53BP1 by GSK3beta revealed that the S/T-Q motif may
      play a critical role. Importantly, our in vivo and in vitro data clearly
      indicated that GSK3beta induced the phosphorylation of 53BP1 at the Ser166 site.
      Moreover, brain tumor xenograft models revealed that following exposure to IR
      plus SB216763, a specific GSK3beta inhibitor, tumor growth was markedly inhibited
      and the survival of mice markedly increased. Based on these results, we concluded
      that the phosphorylation of 53BP1 by GSK3beta was indispensable for DNA DSB
      repair. Our study also suggested that the inhibition of GSK3beta by SB216763
      significantly inhibited the proliferation and induced the apoptosis of
      glioblastoma cells. Taken together, our data indicate that GSK3beta, a key
      phosphorylation protein for 53BP1, may be a potential target for enhancing the
      sensitivity of glioblastoma cells to radiation.

PMID- 29328364
TI  - Genetically-modified stem cells in treatment of human diseases: Tissue kallikrein
      (KLK1)-based targeted therapy (Review).
AB  - The tissue kallikrein-kinin system (KKS) is an endogenous multiprotein metabolic
      cascade which is implicated in the homeostasis of the cardiovascular, renal and
      central nervous system. Human tissue kallikrein (KLK1) is a serine protease,
      component of the KKS that has been demonstrated to exert pleiotropic beneficial
      effects in protection from tissue injury through its anti-inflammatory, anti
      apoptotic, anti-fibrotic and anti-oxidative actions. Mesenchymal stem cells
      (MSCs) or endothelial progenitor cells (EPCs) constitute populations of well
      characterized, readily obtainable multipotent cells with special
      immunomodulatory, migratory and paracrine properties rendering them appealing
      potential therapeutics in experimental animal models of various diseases. Genetic
      modification enhances their inherent properties. MSCs or EPCs are competent
      cellular vehicles for drug and/or gene delivery in the targeted treatment of
      diseases. KLK1 gene delivery using adenoviral vectors or KLK1 protein infusion
      into injured tissues of animal models has provided particularly encouraging
      results in attenuating or reversing myocardial, renal and cerebrovascular
      ischemic phenotype and tissue damage, thus paving the way for the administration
      of genetically modified MSCs or EPCs with the human tissue KLK1 gene. Engraftment
      of KLK1-modified MSCs and/or KLK1-modified EPCs resulted in advanced beneficial
      outcome regarding heart and kidney protection and recovery from ischemic insults.
      Collectively, findings from pre-clinical studies raise the possibility that
      tissue KLK1 may be a novel future therapeutic target in the treatment of a wide
      range of cardiovascular, cerebrovascular and renal disorders.

PMID- 29328368
TI  - Identification of significant biomarkers and pathways associated with gastric
      carcinogenesis by whole genome-wide expression profiling analysis.
AB  - The incidence of gastric cancer (GC) is extremely high in East Asia. GC is also
      one of the most common and lethal forms of cancer from a global perspective.
      However, to date, we have not been able to determine one or several genes as
      biomarkers in the diagnosis of GC and have also been unable to identify the genes
      which are important in the therapy of GC. In this study, we analyzed all genome
      wide expression profiling arrays uploaded onto the Gene Expression Omnibus (GEO)
      database to filtrate the differentially expressed genes (DEGs) between normal
      stomach tissues and GC tissues. GSE13911, GSE19826 and GSE79973 were based on the
      GPL570 platform, and GSE29272 was based on the GPL96 platform. We screened out
      the DEGs from the two platforms and by selecting the intersection of these two
      platforms, we identified the common DEGs in the sequencing data from different
      laboratories. Finally, we obtained 3 upregulated and 34 downregulated DEGs in GC
      from 384 samples. As the number of downregulated DEGs was greater than that of
      the upregulated DEGs, functional analysis and pathway enrichment analysis were
      performed on the downregulated DEGs. Through our analysis, we identified the most
      significant genes associated with GC, such as secreted phosphoprotein 1 (SPP1),
      sulfatase 1 (SULF1), thrombospondin 2 (THBS2), ATPase H+/K+ transporting beta
      subunit (ATP4B), gastric intrinsic factor (GIF) and gastrokine 1 (GKN1). The
      prognostic power of these genes was corroborated in the Oncomine database and by
      Kaplan-Meier plotter (KM-plotter) analysis. Moreover, gastric acid secretion,
      collecting duct acid secretion, nitrogen metabolism and drug metabolism were
      significantly related to GC. Thus, these genes and pathways may be potential
      targets for improving the diagnosis and clinical effects in patients with GC.

PMID- 29328367
TI  - Tumorigenic proteins upregulated in the MYCN-amplified IMR-32 human neuroblastoma
      cells promote proliferation and migration.
AB  - Childhood neuroblastoma is one of the most common types of extra-cranial cancer
      affecting children with a clinical spectrum ranging from spontaneous regression
      to malignant and fatal progression. In order to improve the clinical outcomes of
      children with high-risk neuroblastoma, it is crucial to understand the
      tumorigenic mechanisms that govern its malignant behaviors. MYCN proto-oncogene,
      bHLH transcription factor (MYCN) amplification has been implicated in the
      malignant, treatment-evasive nature of aggressive, high-risk neuroblastoma. In
      this study, we used a SILAC approach to compare the proteomic signatures of MYCN
      amplified IMR-32 and non-MYCN-amplified SK-N-SH human neuroblastoma cells.
      Tumorigenic proteins, including fatty-acid binding protein 5 (FABP5), L1-cell
      adhesion molecule (L1-CAM), baculoviral IAP repeat containing 5 [BIRC5
      (survivin)] and high mobility group protein A1 (HMGA1) were found to be
      significantly upregulated in the IMR-32 compared to the SK-N-SH cells and mapped
      to highly tumorigenic pathways including, MYC, MYCN, microtubule associated
      protein Tau (MAPT), E2F transcription factor 1 (E2F1), sterol regulatory element
      binding transcription factor 1 or 2 (SREBF1/2), hypoxia-inducible factor 1alpha
      (HIF-1alpha), Sp1 transcription factor (SP1) and amyloid precursor protein (APP).
      The transcriptional knockdown (KD) of MYCN, HMGA1, FABP5 and L1-CAM significantly
      abrogated the proliferation of the IMR-32 cells at 48 h post transfection. The
      early apoptotic rates were significantly higher in the IMR-32 cells in which
      FABP5 and MYCN were knocked down, whereas cellular migration was significantly
      abrogated with FABP5 and HMGA1 KD compared to the controls. Of note, L1-CAM,
      HMGA1 and FABP5 KD concomitantly downregulated MYCN protein expression and MYCN
      KD concomitantly downregulated L1-CAM, HMGA1 and FABP5 protein expression, while
      survivin protein expression was significantly downregulated by MYCN, HMGA1 and
      FABP5 KD. In addition, combined L1-CAM and FABP5 KD led to the concomitant
      downregulation of HMGA1 protein expression. On the whole, our data indicate that
      this inter-play between MYCN and the highly tumorigenic proteins which are
      upregulated in the malignant IMR-32 cells may be fueling their aggressive
      behavior, thereby signifying the importance of combination, multi-modality
      targeted therapy to eradicate this deadly childhood cancer.

PMID- 29328370
TI  - Ammonium tetrathiomolybdate enhances the antitumor effects of cetuximab via the
      suppression of osteoclastogenesis in head and neck squamous carcinoma.
AB  - Head and neck squamous cell carcinoma (HNSCC) poses a significant challenge
      clinically where one of the mechanisms responsible for the invasion into facial
      bones occurs via the activation of osteoclasts. Copper has been demonstrated to
      play a key role in skeletal remodeling. However, the role of copper in cancer
      associated bone destruction is thus far unknown. Lysyl oxidase (LOX) is a copper
      dependent enzyme that promotes osteoclastogenesis. In the present study, we
      investigated the effects of copper on HNSCC with bone invasion by the copper
      chelator, ammonium tetrathiomolybdate (TM) in vitro and in vivo. We demonstrate
      that TM blocks the proliferation of HNSCC cells, inhibits LOX activation and
      decreases the expression of the receptor activator of nuclear factor-kappaB
      ligand (RANKL) in osteoblasts and osteocytes, subsequently suppressing bone
      destruction. These findings suggest that copper is a potential target for the
      treatment of HNSCCs associated with bone destruction.

PMID- 29328369
TI  - PITX2 DNA-methylation predicts response to anthracycline-based adjuvant
      chemotherapy in triple-negative breast cancer patients.
AB  - Triple-negative breast cancer (TNBC) constitutes a heterogeneous breast cancer
      subgroup with poor prognosis; survival rates are likely to be lower with TNBC
      compared to other breast cancer subgroups. For this disease, systemic adjuvant
      chemotherapy regimens often yield suboptimal clinical results. To improve
      treatment regimens in TNBC, identification of molecular biomarkers may help to
      select patients for individualized adjuvant therapy. Evidence has accumulated
      that determination of the methylation status of the PITX2 gene provides a
      predictive value in various breast cancer subgroups, either treated with
      endocrine-based therapy or anthracycline-containing chemotherapy. To further
      explore the validity of this novel predictive candidate biomarker, in the present
      exploratory retrospective study, determination of the PITX2 DNA-methylation
      status was assessed for non-metastatic TNBC patients treated with adjuvant
      anthracycline-based chemotherapy by molecular analysis of breast cancer tissues.
      The PITX2 DNA-methylation status was determined in fresh-frozen tumor tissue
      specimens (n=56) by methylation-specific qRT-PCR (qMSP) and the data related to
      disease-free and overall survival, applying an optimized DNA-methylation score of
      6.35%. For non-metastatic TNBC patients treated with adjuvant systemic
      anthracycline-based chemotherapy, a low PITX2 DNA-methylation status (<6.35)
      defines TNBC patients with poor disease-free and overall survival. Univariate and
      multivariate analyses demonstrate the statistically independent predictive value
      of PITX2 DNA-methylation. For non-metastatic TNBC patients, selective
      determination of the PITX2 DNA-methylation status may serve as a cancer biomarker
      for predicting response to anthracycline-based adjuvant chemotherapy. The assay
      based on methylation of the PIXT2 gene can be applied to frozen and routinely
      available formalin-fixed, paraffin-embedded (FFPE) breast cancer tumor tissues
      that will not only define those TNBC patients who may benefit from anthracycline
      based chemotherapy but also those who should be spared the necessity of such
      potentially toxic treatment. Such patients should be allocated to alternative
      treatment options.

PMID- 29328371
TI  - CD133 expression predicts post-operative recurrence in patients with colon cancer
      with peritoneal metastasis.
AB  - Despite extensive research on cancer stem cells in colorectal cancer, the impact
      of stem cell markers on patient survival remains unclear, particularly in those
      with distant metastasis. In this study, we focused on colon cancer with
      peritoneal metastasis and investigated the association between the expression of
      CD133, aldehyde dehydrogenase-1 (ALDH1) and leucine-rich repeating G-protein
      coupled receptor-5 (Lgr5), and disease prognosis. Putative stem cell marker
      expression was immunohistochemically evaluated in samples from 142 primary
      tumours and 75 peritoneal nodules. The associations between the expression of
      these markers and clinicopathological characteristics, overall survival and
      disease-free survival were analysed. The expression of CD133, ALDH1 and Lgr5 was
      found to be positive in 55.6, 47.2 and 78.9% of the primary tumour samples,
      respectively. While their expression was not associated with overall survival,
      disease-free survival was significantly worse in the CD133-negative group (36.1
      vs. 13.7%, P=0.041). Multivariable analysis confirmed that a negative CD133
      expression was an independent risk factor for a reduced disease-free survival
      (P=0.005). Furthermore, the benefit of systemic chemotherapy was significantly
      greater in the CD133-negative group (P=0.039). On the whole, our data indicated
      that patients with colon cancer with CD133-negative expression had a reduced
      disease-free survival. Thus, we propose that CD133 expression may be a useful
      clinical biomarker in the treatment of colon cancer with peritoneal metastasis.

PMID- 29328372
TI  - Differential microRNA expression profiles and bioinformatics analysis between
      young and aging spontaneously hypertensive rats.
AB  - MicroRNAs (miRNAs/miRs) serve a role as important regulators in cardiac
      hypertrophy. The present study aimed to reveal the differential expression
      profile of miRNAs between young and aging spontaneously hypertensive rats (SHRs)
      and studied the functional annotation of predicted targets. Briefly, 3-month-old
      and 12-month-old SHRs (n=3/group) were subjected to echocardiography,
      histopathological analysis and dihydroethidium staining. Subsequently, small RNA
      sequencing and data processing was conducted to identify the differentially
      expressed miRNAs between these two groups. Eight significantly upregulated miRNAs
      were validated by reverse transcription-quantitative polymerase chain reaction
      (RT-qPCR), followed by in silico target gene prediction. Functional annotation
      analysis of the predicted targets was performed using Gene Ontology (GO) and
      Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. As a result,
      significantly impaired left ventricular diastolic function was detected in the 12
      month-old SHRs, alongside increased myocyte cross-sectional area and percentage
      area of fibrosis, elevated reactive oxygen species production and reduced
      microvessel density (P<0.05). Compared with the 3-month-old SHRs, 21 miRNAs were
      significantly upregulated and five miRNAs were downregulated in 12-month-old rats
      (P<0.05). Eight upregulated, remodeling-associated miRNAs, including rno-miR-132
      3p, rno-miR-182, rno-miR-208b-3p, rno-miR-212-3p, rno-miR-214-3p, rno-miR-218a
      5p, rno-miR-221-3p and rno-miR-222-3p, underwent bioinformatics analysis. The
      target genes were significantly enriched in 688 GO terms and 39 KEGG pathways,
      including regulation of peptidyl-tyrosine phosphorylation, regulation of protein
      serine/threonine kinase activity, adrenergic signaling in cardiomyocytes, ErbB
      signaling pathway, mTOR signaling pathway, FoxO signaling pathway, Ras signaling
      pathway, insulin secretion, adipocytokine signaling pathway, HIF-1 signaling
      pathway, Rap1 signaling pathway, VEGF signaling pathway and TNF signaling
      pathway. Collectively, the present study identified a dysregulated miRNA profile
      in aging SHRs, which targeted numerous signaling pathways associated with cardiac
      hypertrophy, autophagy, insulin metabolism, angiogenesis and inflammatory
      response.

PMID- 29328373
TI  - Integrative gene ontology and network analysis of coronary artery disease
      associated genes suggests potential role of ErbB pathway gene EGFR.
AB  - Coronary artery disease (CAD) is a major cause of mortality in India, more
      importantly the young Indians. Combinatorial and integrative approaches to
      evaluate pathways and genes to gain an improved understanding and potential
      biomarkers for risk assessment are required. Therefore, 608 genes from the
      CADgene database version 2.0, classified into 12 functional classes representing
      the atherosclerotic disease process, were analyzed. Homology analysis of the
      unique list of gene ontologies (GO) from each functional class gave 8 GO terms
      represented in 11 and 10 functional classes. Using disease ontology analysis 80
      genes belonging to 8 GO terms, using FunDO suggested that 29 of them were
      identified to be associated with CAD. Extended network analysis of these genes
      using STRING version 9.1 gave 328 nodes and 4,525 interactions of which the top
      5% had a node degree of >=75 associated with pathways including the ErbB
      signaling pathway with epidermal growth factor receptor (EGFR) gene as the
      central hub. Evaluation of EFGR protein levels in age and gender-matched 342 CAD
      patients vs. 342 control subjects demonstrated significant differences
      [controls=149.76+/-2.47 pg/ml and CAD patients stratified into stable angina
      (SA)=161.65+/-3.40 pg/ml and myocardial infarction (MI)=171.51+/-4.26 pg/ml].
      Logistic regression analysis suggested that increased EGFR levels exhibit 3-fold
      higher risk of CAD [odds ratio (OR) 3.51, 95% confidence interval [CI] 1.96-6.28,
      P<=0.001], upon adjustment for hypertension, diabetes and smoking. A unit
      increase in EGFR levels increased the risk by 2-fold for SA (OR 2.58, 95% CI 1.25
      5.33, P=0.01) and 3.8-fold for MI (OR 3.82, 95% CI 1.94-7.52, P<=0.001) following
      adjustment. Thus, the use of ontology mapping and network analysis in an
      integrative manner aids in the prioritization of biomarkers of complex disease.

PMID- 29328374
TI  - ATX-LPA axis facilitates estrogen-induced endometrial cancer cell proliferation
      via MAPK/ERK signaling pathway.
AB  - Autotaxin (ATX) is a key enzyme that converts lysophosphatidylcholine to
      lysophosphatidic acid (LPA). ATX is a crucial factor that facilitates cancer
      progression; however, the effect of ATX on endometrial cancer has not been
      explored. The aim of the present study was to investigate the role of ATX in the
      progression of endometrial cancer. The immunohistochemical results revealed
      higher protein expression levels of ATX and LPA receptors (LPA 1, 2 and 3) in
      human endometrial cancer tissue than in non-carcinoma tissue. In addition,
      reverse transcription-quantitative polymerase chain reaction and western blotting
      analysis demonstrated that ATX and LPA receptor mRNA and protein expression was
      greater in Ishikawa cells, which are positive for estrogen receptor (ER), than in
      Hec-1A cells that exhibit low ER expression. Short interfering RNA knockdown of
      ATX in Ishikawa cells led to decreased cell proliferation and cell colony number,
      as determined by Cell Counting kit-8 and colony formation assays. Estrogen
      stimulated ATX mRNA expression. Inhibition of ATX decreased estrogen and LPA
      induced cell proliferation. High LPA levels markedly elevated the phosphorylation
      levels of extracellular signal-regulated kinase (ERK). ATX downregulation
      moderately decreased estrogen- and LPA-induced phosphorylation of ERK. In
      addition, the ERK inhibitor, PD98059, reduced cell proliferation with estrogen,
      ATX and LPA treatment. The present study suggested that the ATX-LPA axis may
      facilitate estrogen-induced cell proliferation in endometrial cancer via the
      mitogen-activated protein kinase/ERK signaling pathway. The present study may
      provide ideas and an experimental basis for clinicians to identify new molecular
      targeted drugs for the treatment of endometrial cancer.

PMID- 29328376
TI  - Identification of a novel compound heterozygous mutation of the CYP21A2 gene
      causing 21-hydroxylase deficiency in a Chinese pedigree.
AB  - 21-Hydroxylase deficiency (21-OHD) is the most common cause of congenital adrenal
      hyperplasia. Inherited in an autosomal recessive manner, 21-OHD is caused by
      mutations in the cytochrome P450 family 21 subfamily A member 2 (CYP21A2) gene.
      The present study was designed to investigate the genetic characteristics of one
      Chinese pedigree and to identify the genotype-phenotype association, thereby
      facilitating the precise diagnosis of 21-OHD at the molecular level. Members of a
      Chinese family with 21-OHD were screened for mutations in the CYP21A2 gene.
      Clinical data and biochemical parameters, including androgen and derivatives,
      were collected. Complete DNA sequencing and multiplex ligation-dependent probe
      amplification (MLPA) were utilized to analyze the genetic variations in the full
      length CYP21A2 gene. A C-T transition located in exon 8 of the CYP21A2 gene,
      leading to the predicted amino acid residue change from Arg to Trp at codon 342,
      was identified in the mother and four sisters. Additionally, heterozygous
      deletion mutations of exons 1, 3, 4, 6 and 7 of paternal origin were detected in
      the four sisters by MLPA analysis. During the one-year follow-up, the four
      sisters exhibited symptom improvement following treatment with glucocorticoids,
      and the proband and one sister successfully conceived. The results of the present
      study demonstrated that novel compound heterozygous variations in the CYP21A2
      gene may be causative agents of 21-OHD, providing insights into the functions of
      this gene and a more comprehensive understanding of the disorder.

PMID- 29328375
TI  - The role of IL-16 gene polymorphisms in endometriosis.
AB  - Endometriosis is one of the most common gynecological diseases affecting up to
      10% of the female population of childbearing age and a major cause of pain and
      infertility. It is influenced by multiple genetic, epigenetic and environmental
      factors. Interleukin-16 (IL-16) is a proinflammatory cytokine playing a pivotal
      role in many inflammatory and autoimmune diseases as well as in the pathogenesis
      of endometriosis. The aim of the present study was to evaluate the association of
      two IL-16 gene single nucleotide polymorphisms (SNPs), rs4072111 and rs11556218,
      with the risk of endometriosis in women from Greece as well as to gain insight
      about the structural consequences of these two exonic SNPs regarding development
      of the disease. A total of 159 women with endometriosis (stages I-IV)
      hospitalized for endometriosis, diagnosed by laparoscopic intervention and
      histologically confirmed, and 146 normal controls were recruited and genotyped.
      Subjects were genotyped using a polymerase chain reaction restriction fragment
      length polymorphism (PCR-RFLP) strategy. A significant association was detected
      regarding the GG and GT genotype as well as 'G' allele of rs11556218 in patients
      with endometriosis. The rs4072111 SNP of the IL-16 gene was not found to be
      associated with an increased susceptibility to endometriosis either for all
      patients (stages I-IV) or for stage III and IV of the disease only. Our results
      demonstrated that rs11556218 is associated with endometriosis in Greek women,
      probably by resulting in the aberrant expression of IL-16, as suggested by the
      bioinformatics analysis conducted on the SNP-derived protein sequences, which
      indicated a possible association between mutation and functional modification of
      Pro-IL-16.

PMID- 29328377
TI  - Feature genes in metastatic breast cancer identified by MetaDE and SVM classifier
      methods.
AB  - The aim of the present study was to investigate the feature genes in metastatic
      breast cancer samples. A total of 5 expression profiles of metastatic breast
      cancer samples were downloaded from the Gene Expression Omnibus database, which
      were then analyzed using the MetaQC and MetaDE packages in R language. The
      feature genes between metastasis and non-metastasis samples were screened under
      the threshold of P<0.05. Based on the protein-protein interactions (PPIs) in the
      Biological General Repository for Interaction Datasets, Human Protein Reference
      Database and Biomolecular Interaction Network Database, the PPI network of the
      feature genes was constructed. The feature genes identified by topological
      characteristics were then used for support vector machine (SVM) classifier
      training and verification. The accuracy of the SVM classifier was then evaluated
      using another independent dataset from The Cancer Genome Atlas database. Finally,
      function and pathway enrichment analyses for genes in the SVM classifier were
      performed. A total of 541 feature genes were identified between metastatic and
      non-metastatic samples. The top 10 genes with the highest betweenness centrality
      values in the PPI network of feature genes were Nuclear RNA Export Factor 1,
      cyclin-dependent kinase 2 (CDK2), myelocytomatosis proto-oncogene protein (MYC),
      Cullin 5, SHC Adaptor Protein 1, Clathrin heavy chain, Nucleolin, WD repeat
      domain 1, proteasome 26S subunit non-ATPase 2 and telomeric repeat binding factor
      2. The cyclin-dependent kinase inhibitor 1A (CDKN1A), E2F transcription factor 1
      (E2F1), and MYC interacted with CDK2. The SVM classifier constructed by the top
      30 feature genes was able to distinguish metastatic samples from non-metastatic
      samples [correct rate, specificity, positive predictive value and negative
      predictive value >0.89; sensitivity >0.84; area under the receiver operating
      characteristic curve (AUROC) >0.96]. The verification of the SVM classifier in an
      independent dataset (35 metastatic samples and 143 non-metastatic samples)
      revealed an accuracy of 94.38% and AUROC of 0.958. Cell cycle associated
      functions and pathways were the most significant terms of the 30 feature genes. A
      SVM classifier was constructed to assess the possibility of breast cancer
      metastasis, which presented high accuracy in several independent datasets. CDK2,
      CDKN1A, E2F1 and MYC were indicated as the potential feature genes in metastatic
      breast cancer.

PMID- 29328378
TI  - Liposome-delivered baicalein induction of myeloid leukemia K562 cell death via
      reactive oxygen species generation.
AB  - Baicalein (BL), a potential cancer chemopreventative flavone, has been reported
      to inhibit cancer cell growth by inducing apoptosis and causing cell cycle arrest
      in various human cancer cell models. Delivery of BL via nanoliposomes has been
      shown to improve its oral bioavailability and long-circulating property in vivo.
      However, the role of BL in the inhibition of human chronic myeloid leukemia (CML)
      K562 cell growth and its underlying mechanisms has yet to be elucidated. In the
      present study, BL was formulated into liposomes with different sizes to improve
      its solubility and stability. The cytotoxic and pro-apoptotic effects of free BL
      and liposomal BL were also evaluated. The results demonstrated that 100 nm
      liposomes were the most stable formulation when compared with 200 and 400 nm
      liposomes. Liposomal BL inhibited K562 cell growth as efficiently as free BL
      (prepared in DMSO), indicating that the liposome may be a potential vehicle to
      deliver BL for the treatment of CML. Flow cytometry analysis showed that there
      was significant (P<0.005) cell cycle arrest in the sub-G1 phase (compared with
      vehicle control), indicating cell apoptosis following 20 uM liposomal BL or free
      BL treatment of K562 cells for 48 h. The induction of cell apoptosis by all BL
      preparations was further confirmed through the staining of treated cells with
      Annexin V-fluorescein isothiocyanate/propidium iodide. A significant increase in
      reactive oxygen species (ROS) gene-ration was observed in free BL and liposomal
      BL treated cells, with a higher level of ROS produced from those treated with
      free BL. This indicated that cell apoptosis induced by BL may be via ROS
      generation and liposome delivery may further extend the effect through its long
      circulating property.

PMID- 29328379
TI  - miR-1273g-3p promotes proliferation, migration and invasion of LoVo cells via
      cannabinoid receptor 1 through activation of ERBB4/PIK3R3/mTOR/S6K2 signaling
      pathway.
AB  - MicroRNAs (miR) are important in various crucial cell processes including
      proliferation, migration and invasion. Dysregulation of miRNAs have been
      increasingly reported to contribute to colorectal cancer. However, the detailed
      biological function and potential mechanisms of miR-1273g-3p in colorectal cancer
      remain poorly understood. The expression levels of miR-1273g-3p in human
      colorectal cancer LoVo cell lines were detected via reverse transcription
      quantitative polymerase chain reaction (RT-qPCR). The target genes of miR-1273g
      3p were predicted by bioinformatics and verified by a luciferase reporter assay,
      RT-qPCR and western blotting. The MTT, wound-healing and Transwell assays were
      used to examine the biological functions of miR-1273g-3p in LoVo cells. The
      potential molecular mechanisms of miR-1273g-3p on LoVo cell proliferation,
      migration and invasion was detected by western blotting. The results of the
      present study demonstrated that miR-1273g-3p expression was extensively
      upregulated in LoVo cells compared with the normal colon epithelial NCM460 cell
      line. Further studies indicated that miR-1273g-3p inhibitor significantly
      suppressed LoVo cell proliferation, migration and invasion compared with
      inhibitor control. Following this, the cannabinoid receptor 1 (CNR1) was
      identified as a direct target gene of miR-1273g-3p. Knockdown of CNR1 restored
      the phenotypes of LoVo cells transfected with miR-1273g-3p inhibitor.
      Furthermore, the potential molecular mechanism of miR-1273g-3p on LoVo cell
      proliferation, migration and invasion may be mediated by activating the Erb-B2
      receptor tyrosine kinase 4 (ERBB4)/phosphoinositide-3-kinase regulatory subunit 3
      (PIK3R3)/mechanistic target of rapamycin (mTOR)/S6 kinase 2 (S6K2) signaling
      pathway. These observations indicated that miR-1273g-3p promoted the
      proliferation, migration and invasion of LoVo cells via CNR1, and this may have
      occurred through activation of the ERBB4/PIK3R3/mTOR/S6K2 signaling pathway,
      suggesting that miR-1273g-3p may serve as a novel therapeutic target for the
      effective treatment of colorectal cancer.

PMID- 29328380
TI  - Role of the PI3K-AKT-mTOR pathway in hepatitis B virus infection and replication.
AB  - The replication of hepatitis B virus (HBV) may be modulated by a variety of cell
      signaling pathways, including the phosphatidylinositol 3-kinase (PI3K)-RAC-alpha
      serine/threonine-protein kinase (AKT)-serine/threonine-protein kinase mTOR (mTOR)
      pathway. The aim of the present study was to determine the regulatory effects of
      this pathway on the infection and replication of HBV. The results indicated that
      the HBV entry process may activate the AKT pathway, as demonstrated by AKT
      phosphorylation in HBV natural infection. However, inhibition of AKT
      phosphorylation by short-term treatment with AKT inhibitors was unable to block
      HBV entry, which suggested that AKT activation induced by HBV infection is not
      essential for viral entry process. Prolonged treatment with PI3K-AKT-mTOR pathway
      inhibitors markedly promoted HBV replication in HBV replicating and natural
      infection models. The PI3K-AKT-mTOR pathway was therefore identified to be a
      negative regulator of HBV replication. These inhibitors enhanced the replication
      and transcription of HBV in an HBx-dependent way. The results additionally
      indicated that a PI3K inhibitor, Ly294002, inhibited the secretion of the small
      surface antigen of HBV in a PI3K-AKT-independent manner. The inhibitor Ly294002
      may be used as a tool for the drug development of surface antigen secretion
      inhibitors.

PMID- 29328381
TI  - Overexpressing microRNA-150 attenuates hypoxia-induced human cardiomyocyte cell
      apoptosis by targeting glucose-regulated protein-94.
AB  - MicroRNA (miR)-150 has been demonstrated to protect the heart from ischemic
      injury. However, the protective effect of miR-150 in hypoxia-injured
      cardiomyocytes remains unclear. The present study aimed to investigate the target
      gene of miR-150 and the underlying molecular mechanisms of miR-150 in hypoxia
      induced cardiomyocyte apoptosis. Using the hypoxia model of human cardiomyocytes
      (HCMs) in vitro, it was demonstrated that miR-150 was markedly inhibited in HCMs
      after hypoxia treatment. Overexpressing miR-150 significantly decreased hypoxia
      induced HCM death and apoptosis. In addition, GRP94 was revealed to be a direct
      target of miR-150. Additionally, GRP94 was demonstrated to be involved in hypoxia
      induced HCM apoptosis, and the protein expression levels of GRP94 were increased
      in HCMs in the presence of hypoxia. These findings demonstrated that miR-150 is
      involved in hypoxia-mediated gene regulation and apoptosis in HCMs. Furthermore,
      GRP94 knockout increased the cell viability of hypoxia-impaired HCMs with miR-150
      mimic or miR-150 inhibitor transfection. In conclusion, miR-150 may serve a
      protective role in cardiomyocyte hypoxia injury, and the underlying mechanism was
      mediated, at least partially, by inhibiting GRP94 expression. These findings may
      provide a novel insight for the therapy of hypoxia-induced myocardial I/R injury.

PMID- 29328382
TI  - Propofol postconditioning protects H9c2 cells from hypoxia/reoxygenation injury
      by inducing autophagy via the SAPK/JNK pathway.
AB  - Propofol postconditioning (P-PostC) offers cardioprotection in mice, and the
      upregulation of autophagy protects cardiac cells against ischemia/reperfusion
      injury. The present study aimed to examine the effects of P-PostC on the
      induction of autophagy and its potential roles in hypoxia/reoxygenation (H/R)
      injury. Rat heart-derived H9c2 cells were exposed to H/R, comprising 6 h of
      hypoxia followed by 4 h of reoxygenation, as well as postconditioning with
      various concentrations of propofol at the onset of reperfusion. Lactate
      dehydrogenase (LDH) activity and the rate of cell apoptosis were measured to
      evaluate the degree of cardiomyocyte H/R injury. The induction of autophagy in
      myocytes subjected to H/R injury and P-PostC was detected by western blotting and
      immunofluorescence. Furthermore, the activation of c-Jun N-terminal kinase (JNK)
      in cells treated with P-PostC with or without co-treatment with SP600125, an
      inhibitor of JNK, was also determined by western blotting. P-PostC reduced the
      activity of LDH in the culture medium and the percentage of apoptotic cells
      compared with cells in the untreated H/R group. In addition, P-PostC induced
      autophagy and promoted survival signaling in H9c2 cardiac myoblast cells. The
      inhibition of autophagy by 3-methyladenine treatment diminished the
      cardioprotective effects of P-PostC. These results indicated that propofol
      postconditioning promoted cell survival through the induction of autophagy in
      H9c2 cardiac cells, and that the stress-activated protein kinase/JNK survival
      pathway may be partly involved in P-PostC-induced autophagy.

PMID- 29328383
TI  - Oxymatrine protects against the effects of cardiopulmonary resuscitation via
      modulation of the TGF-beta1/Smad3 signaling pathway.
AB  - Previous studies have demonstrated that oxymatrine may inhibit ventricular
      remodeling and serves an important role in the treatment of cardiovascular
      disease. The present study investigated whether oxymatrine treatment protects
      against the effects of cardiopulmonary resuscitation (CPR) via regulation of the
      transforming growth factor-beta1 (TGF-beta1)/mothers against decapentaplegic
      (Smad) signaling pathway. A CPR model was established in Sprague-Dawley (SD) rats
      by asphyxiation, and rats were subsequently anaesthetized by intraperitoneal
      injection of chloral hydrate. SD rats were then administered 25 or 50 mg/kg
      oxymatrine once a day for 4 weeks. Oxymatrine treatment significantly improved
      troponin I levels, the ejection fraction, hydroxyproline content and the
      myocardial performance index in model rats. However, treatment with oxymatrine
      significantly reduced arterial oxygen tension, arterial lactate levels and oxygen
      extraction. Treatment with oxymatrine following CPR significantly inhibited the
      protein expression levels of TGF-beta1, TGF-beta1 receptor type 1 and Smad
      homolog 3 (Smad3) in model rats. The results of this research indicated that
      oxymatrine treatment may protect against the effects of CPR via regulation of the
      TGF-beta1/Smad3 signaling pathway and may be a novel drug for CPR in a clinical
      setting.

PMID- 29328384
TI  - Forkhead box protein C1 promotes cell proliferation and invasion in human
      cervical cancer.
AB  - Increasing evidence has demonstrated that aberrant forkhead box protein C1
      (FOXC1) expression contributes to tumorigenesis in multiple types of malignant
      tumor. However, the clinical significance and biological roles of FOXC1 in
      cervical cancer remain unknown. The expression levels of FOXC1 were examined in
      human cervical cancer tissues and cells using reverse transcription-quantitative
      polymerase chain reaction, immunohistochemistry and western blotting.
      Furthermore, high FOXC1 expression was significantly associated with advanced
      clinical stages, a high degree of malignancy and a poor outcome. FOXC1 silencing
      inhibited cell growth and enhanced cell apoptosis. Knockdown of FOXC1 markedly
      suppressed cell migration and invasion in vitro, and resulted in downregulation
      of phosphorylated-RAC-alpha serine/threonine-protein kinase, proto-oncogene c-Myc
      and B-cell lymphoma 2. In conclusion, these data indicated that upregulation of
      FOXC1 contributed to the development of cervical cancer by increasing the growth
      and motility of the cervical cancer cells, thereby worsening the disease
      progression in these patients.

PMID- 29328385
TI  - Tormentic acid inhibits IL-1beta-induced chondrocyte apoptosis by activating the
      PI3K/Akt signaling pathway.
AB  - Interleukin-1beta (IL-1beta) accelerates degradation of the cartilage matrix and
      induces apoptosis of chondrocytes. Tormentic acid (TA) is a triterpene isolated
      from the stem bark of the Vochysia divergens plant, which has been demonstrated
      to exert in vitro inhibitory activity against hepatocyte apoptosis. However, the
      effects of TA on IL-1beta-induced apoptosis of human chondrocytes remain unclear.
      Therefore, the present study investigated the in vitro effects of TA on human
      osteoarthritic chondrocyte apoptosis cultivated in the presence of IL-1beta.
      Human chondrocytes were pretreated with or without various concentrations of TA
      and then co-incubated in the absence or presence of IL-1beta for 24 h. Cell
      viability was determined using the MTT assay, and cell apoptosis was detected
      using a Nucleosome ELISA kit. Caspase-3 activity was detected using a caspase-3
      colorimetric assay kit. The levels of B-cell lymphoma 2 (Bcl-2)-associated X
      protein (Bax), Bcl-2, phosphorylated (p)-phosphoinositide 3-kinase (PI3K), PI3K,
      p-protein kinase B (Akt) and Akt were measured by western blotting. The results
      revealed that pretreatment with TA inhibited IL-1beta-induced cytotoxicity and
      apoptosis in chondrocytes. In addition, TA pretreatment increased B-cell lymphoma
      (Bcl)-2 expression, and decreased caspase-3 activity and Bax expressionin human
      chondrocytes. In addition, pretreatment with TA markedly increased the expression
      of p-PI3K and p-Akt in IL-1beta-induced chondrocytes. Collectively, these results
      indicate that TA inhibits IL-1beta-induced chondrocyte apoptosis by activating
      the PI3K/Akt signaling pathway. Therefore, TA may be considered a potential
      therapeutic target for the treatment of osteoarthritis.

PMID- 29328386
TI  - Proteomics-based investigation of multiple stages of OSCC development indicates
      that the inhibition of Trx-1 delays oral malignant transformation.
AB  - The majority of cases of oral squamous cell carcinoma (OSCC) develop from oral
      potentially malignant disorders, which have been confirmed to be involved in
      chronic oxidative stimulation. However, no effective treatment approaches have
      been used to prevent the development of dysplasia into cancerous lesions thus
      far. In the present study, a well-established OSCC model was used to detect
      proteomics profiles at different stages during oral malignant transformation. Of
      the 15 proteins that were found to be upregulated in both the dysplasia and
      carcinoma stages, the oxidative stress-associated proteins, thioredoxin-1 (Trx
      1), glutaredoxin-1 and peroxiredoxin-2 were note as the proteins with significant
      changes in expression Trx-1 was identified to be the most significantly
      upregulated protein in the precancerous stage. Validation experiments confirmed
      that Trx-1 was overexpressed both in dysplasia and cancerous tissue samples, and
      the inhibition of Trx-1 was able to promote the apoptosis of OSCC cells under
      hypoxic conditions. Furthermore, the experimental application of a Trx-1-specific
      inhibitory agent in an animal model led to a lower cancerization rate and a delay
      in tumor formation. The possible mechanisms were associated with the increased
      apoptosis via a reactive oxygen species (ROS)-dependent pathway. Taken together,
      our findings indicate that Trx-1 may be an important target for delaying oral
      malignant transformation, which provides a novel therapeutic strategy for the
      prevention and treatment of OSCC.

PMID- 29328387
TI  - Rhus verniciflua Stokes extract induces inhibition of cell growth and apoptosis
      in human chronic myelogenous leukemia K562 cells.
AB  - Rhus verniciflua Stokes has been widely used as a traditional medicinal plant
      with a variety of pharmacological activities. We investigated the mechanisms
      involved in mediating the effects of Rhus verniciflua Strokes (R. verniciflua)
      extract in human chronic myelogenous leukemia K562 cells, including caspase
      dependent apoptotic pathways related to cell-cycle arrest, as well as the
      inhibition of nuclear factor NF-kappaB activation and upregulation of the mitogen
      activated protein kinase (MAPK) signaling pathway. R. verniciflua extract
      suppressed the abnormal cellular proliferation of K562 cells in a dose- and time
      dependent manner and increased the quantitative proportions of cells involved in
      the early and late process of apoptosis. Furthermore, R. verniciflua extract
      significantly mediated the mRNA levels of pro-apoptotic and anti-apoptotic
      regulators, such as Bcl-2, Bax, Mcl-1 and survivin in apoptotic cells.
      Particularly, the treatment of K562 cells with R. verniciflua extract augmented
      the caspase-3 activity and increased the expression of caspase-3 protein, while
      co-treatment with R. verniciflua extract and the permeant pan-caspase inhibitor Z
      VAD-FMK and caspase-3 inhibitor Z-DEVD-FMK inversely enhanced the proliferation
      of K562 cells. The extract of R. verniciflua inhibited the activation of NF
      kappaB and the phosphorylation of ERK. Collectively, these results indicated that
      the extract of R. verniciflua inhibited the proliferation of human chronic
      myelogenous leukemia K562 cells by activating the apoptotic process via caspase-3
      overexpression and the regulation of the NF-kappaB and MAPK signaling.

PMID- 29328389
TI  - miR-375 inhibits IFN-gamma-induced programmed death 1 ligand 1 surface expression
      in head and neck squamous cell carcinoma cells by blocking JAK2/STAT1 signaling.
AB  - Upregulation of programmed death 1 ligand 1 (PD-L1) in cancer cells and its
      ligation to PD-1 on T cells facilitates cancer cell escape from immune
      surveillance. Therapies with PD-1 or PD-L1 antibodies have resulted in marked
      clinical responses in various cancer types. Hence, modulators that inhibit PD-L1
      expression in cancer cells may serve as a novel strategy by which to enhance host
      immune responses. In the present study, we investigated the effects of miR-375 on
      PD-L1 expression in head and neck squamous cell carcinoma (HNSCC) cells by qRT
      PCR and western blot analyses. We confirmed that miR-375 inhibited IFN-gamma
      induced PD-L1 surface expression in HNSCC cells, and we observed that Janus
      kinase 2 (JAK2) is a bona fide target of miR-375 and further activated signal
      transducer and activator of transcription 1 (STAT1). Additionally, miR-375
      mediated inhibition of PD-L1 expression was dependent on the JAK2/STAT1 pathway.
      Therefore, by attenuating PD-1/PD-L1 signaling, miR-375 may also serve as a
      modulator to increase the cell immune responses to HNSCC.

PMID- 29328388
TI  - GW4064 attenuates lipopolysaccharide-induced hepatic inflammation and apoptosis
      through inhibition of the Toll-like receptor 4-mediated p38 mitogen-activated
      protein kinase signaling pathway in mice.
AB  - Liver injury is associated with devastating consequences caused by inflammation
      and apoptosis. The farnesoid X receptor (FXR) is a nuclear receptor that has an
      essential role in hepatoprotection by maintaining the homeostasis of liver
      metabolism. The present study investigated the capacity of the FXR agonist GW4064
      to protect the livers of mice from lipopolysaccharide (LPS)-induced inflammation
      and apoptosis. Male C57BL/6J [wild-type (WT)] and FXR knockout (KO) mice were
      intraperitoneally injected with LPS or saline. LPS-treated mice were
      intraperitoneally injected with vehicle or GW4064 (20 mg/kg) twice and then
      sacrificed. Activation of FXR by GW4064 alleviated hepatic inflammation in the
      LPS-induced murine liver injury model as reflected by reduced serum levels of
      aspartate aminotransferase and pro-inflammatory cytokine mRNA expression,
      including tumor necrosis factor-alpha, as well as interleukin-6 and -1beta in WT
      mice. In addition, Toll-like receptor 4 (TLR4), p38 mitogen-activated protein
      kinase (MAPK), B-cell lymphoma-2-associated X protein and cytochrome c protein
      levels were decreased in WT mice receiving LPS with simultaneous GW4064
      administration compared with those receiving LPS alone, while this was not
      observed in FXR KO mice. These results indicated that in WT mice, administration
      of GW4064 ameliorated LPS-mediated liver injury by upregulation of FXR
      expression, which was in part mediated by the TLR4/p38 MAPK pathway.

PMID- 29328391
TI  - Effects of thymosin beta4 on oxygen-glucose deprivation and reoxygenation-induced
      injury.
AB  - Cerebral ischemia causes severe brain injury and results in selective neuronal
      death through programmed cell death mechanisms, including apoptosis and
      autophagy. Minimizing neuronal injury has been considered a hot topic among
      clinicians. The present study elucidated the effect of thymosin beta4 (Tbeta4) on
      neuronal death induced by cerebral ischemia/reperfusion in PC12 cells that were
      subjected to oxygen-glucose deprivation and reoxygenation (OGD/R). The survival,
      apoptotic and autophagy rates of PC12 cells were investigated. Tbeta4 pre
      conditioning prior to OGD/R was performed to evaluate PC12-cell viability and the
      protective mechanisms of Tbeta4. Tbeta4 significantly increased cell survival
      after OGD/R. Tbeta4 inhibited the release of lactate dehydrogenase, downregulated
      malondialdehyde and upregulated the activities of glutathione peroxidase and
      superoxide dismutase. In addition, Tbeta4 attenuated OGD/R-associated decreases
      in the expression of P62 and the anti-apoptotic protein B-cell lymphoma-2, as
      well as the upregulation of autophagy mediators, including autophagy-related
      protein-5 and the ratio of microtubule-associated protein 1 light chain 3 (LC3)
      II vs. LC3 I. These results suggested that Tbeta4 effectively inhibits cell
      apoptosis and autophagy induced by OGD/R. To the best of our knowledge, the
      present study was the first to report on the antioxidant, anti-apoptotic and anti
      autophagic effects of Tbeta4 in neuronal-like PC12 cells. These results suggested
      that Tbeta4 may be explored as a potential treatment for cerebral ischemia.

PMID- 29328390
TI  - Investigation into the underlying molecular mechanisms of hypertensive
      nephrosclerosis using bioinformatics analyses.
AB  - Hypertensive nephrosclerosis (HNS) is a major risk factor for end-stage renal
      disease. However, the underlying pathogenesis of HNS remains to be fully
      determined. The gene expression profile of GSE20602, which consists of 14
      glomeruli samples from patients with HNS and 4 normal glomeruli control samples,
      was obtained from the Gene Expression Omnibus database. Gene ontology (GO) and
      pathway enrichment analyses were performed in order to investigate the functions
      and pathways of differentially expressed genes (DEGs). Pathway relation and co
      expression networks were constructed in order to identify key genes and signaling
      pathways involved in HNS. In total, 483 DEGs were identified to be associated
      with HNS, including 302 upregulated genes and 181 downregulated genes.
      Furthermore, GO analysis revealed that DEGs were significantly enriched in the
      small molecule metabolic process. In addition, pathway analysis also revealed
      that DEGs were predominantly involved in metabolic pathways. The tricarboxylic
      acid (TCA) cycle was identified as the hub pathway in the pathway relation
      network, whereas the sorbitol dehydrogenase (SORD) and cubulin (CUBN) genes were
      revealed to be the hub genes in the co-expression network. The present study
      revealed that the SORD, CUBN and albumin genes as well as the TCA cycle and
      metabolic pathways are involved in the pathogenesis of HNS. The results of the
      present study may contribute to the determination of the molecular mechanisms
      underlying HNS, and provide insight into the exploration of novel targets for the
      diagnosis and treatment of HNS.

PMID- 29328392
TI  - Targeting bladder cancer using activated T cells armed with bispecific
      antibodies.
AB  - In the present study, we aimed to investigate whether EGFR or HER2 may serve as a
      target for T cell-mediated immunotherapy against human bladder cancer. Expression
      of EGFR and HER2 was detected on the surface of bladder cancer cells, including
      Pumc-91 and T24 cells, and their chemotherapeutic drug-resistant counterparts.
      Activated T cells (ATCs) were generated from healthy PBMCs that were stimulated
      by the combination of anti-CD3 monoclonal antibody and anti-CD28 monoclonal
      antibody in the presence of interleukin-2 for 14 days. The ATCs were then armed
      with chemically hetero-conjugated anti-CD3xanti-EGFR (EGFRBi-Ab) or anti-CD3xanti
      HER2 (HER2Bi-Ab). The specific cytolytic activity of ATCs armed with EGFRBi-Ab or
      HER2Bi-Ab against human bladder cancer cells was evaluated by lactate
      dehydrogenase activity assays in vitro. In contrast to unarmed ATCs, EGFRBi-Ab
      armed ATCs and HER2Bi-Ab-armed ATCs showed increased cytotoxic activity against
      bladder cancer cells. Moreover, Bi-Ab-armed ATCs expressed higher levels of
      activating marker CD69 and secreted more IFN-gamma, TNF-alpha and IL-2 than did
      unarmed ATCs. EGFRBi-Ab- or HER2Bi-Ab-armed ATCs may provide a promising
      immunotherapy for bladder cancer.

PMID- 29328394
TI  - Application of multifunctional nanomaterials in cancer vaccines (Review).
AB  - Tumor immunotherapy has been in development for more than a century. With the
      rapid developments in biotechnology research in recent years, immunotherapy has
      become a promising oncotherapy strategy after surgery, chemotherapy and
      radiotherapy. Cancer vaccines are a promising new treatment strategy and the
      application of nanotechnology in cancer vaccines, greatly enhances their
      effectiveness. Such applications indicate the bright prospects of tumor
      immunotherapy. The multifunctional nanomaterials used in cancer vaccines and
      their practical application in specific cancer vaccines are hereby reviewed. In
      addition, a preliminary analysis of the current and prospective use of
      nanotechnology with the purpose of providing solutions to cancer vaccine
      challenges is presented.

PMID- 29328393
TI  - Paediatric Virology and its interaction between basic science and clinical
      practice (Review).
AB  - The 3rd Workshop on Paediatric Virology, which took place on October 7th, 2017 in
      Athens, Greece, highlighted the role of breast feeding in the prevention of viral
      infections during the first years of life. Moreover, it focused on the long-term
      outcomes of respiratory syncytial virus and rhinovirus infections in prematurely
      born infants and emphasised the necessity for the development of relevant
      preventative strategies. Other topics that were covered included the vaccination
      policy in relation to the migration crisis, mother-to-child transmission of
      hepatitis B and C viruses, vaccination against human papilloma viruses in boys
      and advances on intranasal live-attenuated vaccination against influenza.
      Emphasis was also given to the role of probiotics in the management of viral
      infections in childhood, the potential association between viral infections and
      the pathogenesis of asthma, fetal and neonatal brain imaging and the paediatric
      intensive care of children with central nervous system viral infections.
      Moreover, an interesting overview of the viral causes of perinatal mortality in
      ancient Greece was given, where recent archaeological findings from the Athenian
      Agora's bone well were presented. Finally, different continuing medical
      educational options in Paediatric Virology were analysed and evaluated. The
      present review provides an update of the key topics discussed during the
      workshop.

PMID- 29328395
TI  - Bioinformatic identification of chemoresistance-associated microRNAs in breast
      cancer based on microarray data.
AB  - Breast cancer is the most commonly diagnosed cancer among females, and
      chemoresistance constitutes a major clinical obstacle to the treatment of this
      disease. MicroRNAs (miRNAs) are related to human cancer development, progression
      and drug resistance. To identify breast cancer chemoresistance-associated miRNAs,
      miRNA microarray dataset GSE71142, including five chemoresistant breast cancer
      tissues and five chemosensitive tissues, was downloaded from the Gene Expression
      Omnibus (GEO) database. Differentially expressed miRNAs (DE-miRNAs) were obtained
      by t-test and the potential target genes were predicted by miRWalk2.0. Functional
      and pathway enrichment analysis by WebGestalt was performed for the potential
      target genes of DE-miRNAs. Protein-protein interaction (PPI) network was
      established by STRING database and visualized by Cytoscape software. Enriched
      transcription factors by the target genes were obtained from FunRich. Breast
      cancer-associated miRNA-gene pairs were identified from miRWalk2.0. A total of 22
      DE-miRNAs were screened out, including 10 upregulated miRNAs (e.g., miR-196a-5p)
      and 12 downregulated miRNAs (e.g., miR-4472) in the chemoresistant breast cancer
      tissues, compared with chemosensitive tissues. In total 1,278 target genes were
      screened out, and they were involved in breast cancer-related pathways such as
      pathways in cancer, signaling pathways regulating pluripotency of stem cells,
      endocrine resistance, breast cancer, mTOR signaling and Hippo signaling pathway.
      NOTCH1 and MAPK14 were identified as hub genes in the PPI network. EGR1 and SP1
      were the most enriched transcription factors by the target genes. Several breast
      cancer-associated miRNA-gene pairs including miR-214-TP53 and miR-16-PPM1D were
      identified. The current bioinformatics study of miRNAs based on microarray may
      offer a new understanding into the mechanisms of breast cancer chemoresistance,
      and may identify novel miRNA therapeutic targets.

PMID- 29328396
TI  - Placenta-associated serum exosomal miR-155 derived from patients with
      preeclampsia inhibits eNOS expression in human umbilical vein endothelial cells.
AB  - Preeclampsia (PE) is considered to be initiated by abnormal placentation in early
      pregnancy and results in systemic endothelial cell dysfunction in the second or
      third trimester. MicroRNAs (miRs) expressed in the human placenta can be secreted
      into maternal circulation via exosomes, which are secreted extracellular vesicles
      that serve important roles in intercellular communication. The present study
      hypothesized that upregulation of placenta-associated serum exosomal miR-155 from
      patients with PE may suppress endothelial nitric oxide synthase (eNOS) expression
      in endothelial cells. The results demonstrated that placenta-associated serum
      exosomes from patients with PE decreased nitric oxide (NO) production and eNOS
      expression in primary human umbilical vein endothelial cells (HUVECs).
      Subsequently, an upregulation of placenta-associated serum exosomal miR-155 was
      detected in patients with PE compared with in gestational age-matched normal
      pregnant women. In addition, the results demonstrated that overexpression of
      exosomal miR-155 from BeWo cells was internalized into HUVECs, and was able to
      suppress eNOS expression by targeting its 3'-untranslated region. The results of
      the present study indicated that placenta-associated serum exosomes may inhibit
      eNOS expression in endothelial cell during PE development in humans, and this
      phenomenon may be partly due to increased miR-155 expression in placenta
      associated serum exosomes.

PMID- 29328397
TI  - Aberrant expression of IL-23/IL-23R in patients with breast cancer and its
      clinical significance.
AB  - Breast cancer tissues and adjacent tissues were collected from 32 patients who
      were treated in The Third Hospital of Chengde City. Reverse transcription
      quantitative polymerase chain reaction results demonstrated that, compared with
      the adjacent tissues, interleukin (IL)-23/IL-23 receptor (R) gene expression
      levels were notably higher in breast cancer tissues. Furthermore, IL-23 and IL
      23R expression levels were positively correlated with patients' tumor size, TNM
      stage and metastasis. Recombinant human (rh) IL-23 (10 ng/ml) was used for the
      stimulation of the MCF-7 cell line. Effects of rh IL-23 (10 ng/ml) on cell
      proliferation was detected after MCF-7 cells were incubated with rh IL-23 for 48
      h. Whether pre-treatment with polyclonal antibody (PAb) IL-23p19, a neutralizing
      antibody specific for IL-23, may influence the effects of IL-23 on cell behavior
      was also investigated. Cell proliferation assay and cell apoptosis assay were
      evaluated using MTT assay and flow cytometry assay, respectively. Results
      suggested that PAb IL-23p19 reduced IL-23-induced cell proliferation whereas
      induced IL-23 inhibited cell apoptosis. Western blot analysis was performed for
      the detection of molecules that may be responsible for the aforementioned
      changes. Results indicated that PAb IL-23p19 treatment reduced IL-23-induced
      upregulation of B-cell lymphoma-2 protein expression and activation of the janus
      kinase 2/signal transducer and activator of transcription 3 signaling pathway.
      The present results suggested that IL-23 may be a potential prognosis marker and
      target for the treatment of breast cancer patients.

PMID- 29328398
TI  - Synergistic antitumor effect of brusatol combined with cisplatin on colorectal
      cancer cells.
AB  - Colorectal cancer (CRC) is a common and life-threatening type of malignant
      cancer, which is associated with a high mortality rate. Cisplatin (CDDP) is a
      commonly used chemotherapy drug with significant side effects. Brusatol (BR) is
      one of the principal chemical compounds isolated from the Chinese herb Bruceae
      Fructus, which has been reported to markedly inhibit the proliferation of
      numerous cancer cell lines. The present study aimed to investigate the possible
      synergistic anticancer effects of CDDP combined with BR on CT-26 cells, and to
      evaluate the underlying mechanisms of action. The growth inhibitory effects of
      BR, CDDP, and BR and CDDP cotreatment on CT-26 cells were assessed by MTT assay.
      Cell apoptosis were determined by flow cytometry and western blot analysis. The
      results indicated that compared with single-agent treatment, cotreatment of CT-26
      cells with CDDP and BR synergistically inhibited cell proliferation and increased
      cellular apoptosis. Furthermore, treatment of CT-26 cells with CDDP and BR
      resulted in a marked increase in the release of cytosolic cytochrome c, decreased
      expression of procaspase-3 and procaspase-9, and upregulation of the B-cell
      lymphoma 2 (Bcl-2)-associated X protein/Bcl-2 ratio compared with treatment with
      BR or CDDP alone. These results strongly suggested that the combination of CDDP
      and BR was able to produce a synergistic antitumor effect in CRC cells, thus
      providing a solid foundation for further development of this combination regimen
      into an effective therapeutic method for CRC.

PMID- 29328399
TI  - miR-378a enhances the sensitivity of liver cancer to sorafenib by targeting
      VEGFR, PDGFRbeta and c-Raf.
AB  - Liver cancer is a globally prevalent cancer with poor prognosis. The present
      study investigated the link between microRNA-378a (miR-378a) expression and the
      sensitivity of hepatocellular carcinoma (HCC) and hepatoblastoma (HB) cancers to
      sorafenib therapy. miR-378a expression was determined in liver tissue samples
      from healthy candidates and patients with liver cancer using the reverse
      transcription-quantitative polymerase chain reaction. The antitumor effects of
      miR-378a alone and in combination with sorafenib were investigated in the HB cell
      line HepG2 and the HCC cell line SMMC-7721 with methyl thiazoyl tetrazolium,
      colony formation, flow cytometry and Transwell migration assays. The underlying
      mechanisms were investigated using western blot analysis. miR-378a expression was
      decreased in tissue samples from patients with liver cancer. HCC and HB cell line
      proliferation and invasion ability was inhibited by miR-378a. The combination of
      miR-378a and sorafenib provided the greatest inhibition. Western blot indicated
      that mitogen activated protein kinase signaling pathway proteins, vascular
      endothelial growth factor receptor, platelet derived growth factor receptor beta,
      Raf-1 proto-oncogene, serine/threonine kinase and matrix metallopeptidase 2 were
      regulated by miR-378a alone and to a greater extent when combined with sorafenib.
      Results suggest that miR-378a can inhibit liver cancer cell growth and enhance
      the sensitivity of liver cancer cells to sorafenib-based chemotherapies.

PMID- 29328400
TI  - MicroRNA-146a/NAPDH oxidase4 decreases reactive oxygen species generation and
      inflammation in a diabetic nephropathy model.
AB  - The present study investigated the role of microRNA (miR)-146a in a diabetic
      nephropathy (DN) model, and its molecular mechanism. DN mice were given
      intraperitoneal injections of streptozotocin (55 mg/kg/day) for 5 consecutive
      days as an in vivo DN model. The HK-2 human kidney cell line were exposed to 45%
      D-glucose as an in vitro DN model. Firstly, it was demonstrated that miR-146a
      expression was inhibited and NAPDH oxidase 4 (Nox4) was increased in DN mice. In
      HK-2 cells, overexpression of miR-146a inhibited Nox4 protein expression and
      decreased reactive oxygen species (ROS) generation, oxidative stress and
      inflammation, and suppressed vascular cell adhesion molecule-1 (VCAM-1) and
      intracellular adhesion molecule-1 (ICAM-1) protein expression. Nacetylcysteine, a
      Nox4 inhibitor, was demonstrated to inhibit ROS generation, suppress VCAM-1 and
      ICAM-1 protein expression, and decrease oxidative stress and inflammation in HK-2
      cells following overexpression of miR-146a. In conclusion, these results
      indicated that miR-146a/Nox4 decreases ROS generation and inflammation and
      prevents DN. Therefore, miR-146a may represent a novel anti-inflammatory and 
      oxidative modulator of DN.

PMID- 29328401
TI  - Long non-coding RNA MEG3 functions as a tumour suppressor and has prognostic
      predictive value in human pancreatic cancer.
AB  - Long non-coding RNA (lncRNA) MEG3 has been demonstrated to be a tumour suppressor
      in many malignancies. However, the functional role of MEG3 in pancreatic cancer
      (PC) is unclear. In this study, the expression pattern of MEG3 was evaluated in
      25 samples of microdissected PC tissues and 8 PC cell lines and was compared to
      the expression in adjacent non-cancerous tissues and a human pancreatic normal
      epithelial cell line. Loss of MEG3 expression was observed in both the cancerous
      tissues and cancer cell lines. Although the absence of expression of MEG3 was not
      statistically correlated to either histological grade or TNM stage in the 25
      cases, the prognosis was significantly worse. MEG3 knockdown enhanced cell
      proliferation, promoted cell migration and invasion, induced epithelial
      mesenchymal transition (EMT), increased the sphere-forming ability and cancer
      stem cell (CSC) properties, and decreased the chemosensitivity to gemcitabine in
      vitro. In contrast, forced expression of MEG3 resulted in a reverse effect. In
      conclusion, MEG3 functions as a tumour suppressor in human PC. The underlying
      cause of the poor prognosis induced by low levels of MEG3 expression in PC
      patients might involve EMT induction, enhanced CSC phenotypes and reduced
      chemoresistance, all of which might be associated with Snail activation.

PMID- 29328403
TI  - Arcuate nucleus neurons are not essential for the preprandial peak in plasma
      ghrelin after neonatal monosodium glutamate treatment.
AB  - The aim of the present study was to determine whether arcuate nucleus (ARC)
      lesions affect the ghrelin level in the plasma and the stomach in monosodium
      glutamate (MSG)-treated mice. The aim of the present study was to investigate
      whether the ARC was destroyed in mice treated neonatally with MSG, and whether
      the ARC lesions affect the ghrelin level in the plasma and lipid mobilization in
      MSG-treated mice. The results revealed that MSG led to a marked reduction in ARC
      cresyl violet staining, tyrosine hydroxylase-immunoreactive (IR) neurons and
      neuropeptide Y-IR fibers, compared with saline controls. MSG-treated mice
      exhibited significantly increased body mass compared with saline controls, and
      MSG treatment did not prevent food deprivation-induced decrease in white adipose
      tissue mass compared with controls. Plasma ghrelin levels were significantly
      increased in MSG-treated mice that were fasted for 48 h, compared with the levels
      prior to fasting and re-feeding, and the preprandial peak of plasma ghrelin
      persisted in MSG-treated mice. In summary, the ARC was not found to be essential
      for food deprivation-induced lipid mobilization and preprandial peak in MSG
      treated mice. However, this finding does not mean that ARC neurons do not
      contribute to food sensing and lipid mobilization under normal conditions, as
      compensatory mechanisms may have emerged after the ablation of ARC neurons.

PMID- 29328402
TI  - miR-203-3p participates in the suppression of diabetes-associated osteogenesis in
      the jaw bone through targeting Smad1.
AB  - Certain microRNAs (miRs) have important roles in the maintenance of bone
      development and metabolism, and a variety of miRs are known to be deregulated in
      diabetes. The present study investigated the role of miR-203-3p in the regulation
      of bone loss by assessing jaw bones of a rat model of type 2 diabetes. The
      results indicated that miR-203-3p inhibited osteogenesis in the jaws of diabetic
      rats and in rat bone marrow mesenchymal stem cells cultured in high-glucose
      medium. A luciferase re-porter assay was used to verify the bioinformatics
      prediction that miR-203-3p targets the 3'-untranslated region of Smad1, which is
      an important mediator of the bone morphogenetic protein (BMP)/Smad pathway.
      Overexpression of Smad1 attenuated the miR-203-3p-mediated suppres-sion of
      osteogenic differentiation. It was therefore indicated that the BMP/Smad pathway
      is attenuated and the transforming growth factor-beta/activin pathway is promoted
      by Smad1 reduction. Taken together, it was indicated that miR-203-3p inhibits
      osteogenesis in jaw bones of diabetic rats by targeting Smad1 to inhibit the
      BMP/Smad pathway.

PMID- 29328404
TI  - Chronic oxymatrine treatment induces resistance and epithelial-mesenchymal
      transition through targeting the long non-coding RNA MALAT1 in colorectal cancer
      cells.
AB  - A major reason for colorectal cancer (CRC) chemoresistance is the enhanced
      migration and invasion of cancer cells, such as the cell acquisition of
      epithelial-mesenchymal transition (EMT). Long non-coding RNA (lncRNA) metastasis
      associated lung adenocarcinoma transcript 1 (MALAT1) has been considered as a pro
      oncogene in multiple cancers. However, the precise functional mechanism of lncRNA
      MALAT1 in chemoresistance and EMT is not well known. In the present study, we
      focused on the effect of oxymatrine on CRC cells and further investigated the
      role of MALAT1 in oxymatrine-induced resistance and EMT process. The human CRC
      cell line HT29 was exposed to increasing doses of oxymatrine to establish stable
      cell lines resistant to oxymatrine. The established HT29 oxymatrine resistant
      cells showed an EMT phenotype including specific morphologic changes, enhanced
      migratory and invasive capacity, and downregulation of E-cadherin protein
      expression. Subsequently, high-throughput HiSeq sequencing and RT-qPCR showed
      that lncRNA MALAT1 was significantly upregulated in the oxymatrine resistant
      cells (P<0.01), while knockdown of MALAT1 partially reversed the EMT phenotype in
      HT29 resistant cells. Furthermore, oxymatrine treatment suppressed the migration
      and invasion ability of CRC cells, however, this effect was significantly
      reversed by overexpression of MALAT1. Finally, we investigated the clinical role
      of MALAT1 and found that high lncRNA MALAT1 expression level is associated with
      poor prognosis in CRC patients receiving oxymatrine treatment (P<0.01). In
      conclusion, we demonstrate that lncRNA MALAT1 is a stimulator for oxymatrine
      resistance in CRC and it may provide therapeutic and prognostic information for
      CRC patients.

PMID- 29328407
TI  - Estrogen receptor beta1 activation accelerates resistance to epidermal growth
      factor receptor-tyrosine kinase inhibitors in non-small cell lung cancer.
AB  - Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer-related
      deaths worldwide. Epidermal growth factor receptor-tyrosine kinase inhibitors
      (EGFR-TKIs) have revolutionized the treatment of patients with advanced EGFR
      mutant NSCLC. However, drug resistance eventually develops in the majority of
      patients despite an excellent initial response. The present study aimed to
      investigate the mechanism of acquired resistance to EGFR-TKIs and to explore
      strategies to overcome the resistance to EGFR-TKIs from a gender perspective. PC9
      and Hcc827 cell lines, sensitized to EGFR-TKI, and secondary TKI-resistant PC9-ER
      (erlotinib resistant) and Hcc827-ER cell lines were evaluated for the expression
      of ERbeta1. The proliferative ability of both cell lines was analyzed after
      transfection of siRNA-ERbeta1 using Cell Counting Kit-8 and colony formation
      assays. Extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) and Akt
      activation were detected. The co-inhibition efficiency of erlotinib and
      fulvestrant was analyzed in PC9-ER xenografts. The expression of ERbeta1 was
      investigated in tumor tissues of EGFR-TKI-treated patients, and its correlation
      with clinicopathological factors and progression-free survival (PFS) was
      assessed. The expression of ERbeta1 was upregulated secondary to EGFR-TKIs in PC9
      and Hcc827 cell lines, with beta-estradiol dependence. Both PC9-ER and Hcc827-ER
      cell lines were re-sensitized to erlotinib after downregulation of the expression
      of ERbeta1. ERK1/2 and Akt pathways were activated following the silencing of the
      expression of ERbeta1 in PC9-ER and Hcc827 cell lines. The co-treatment of
      erlotinib and fulvestrant exhibited better growth inhibitory efficiency compared
      with the treatment of each agent alone in PC9-ER-derived xenografts. Primary
      NSCLC samples of 53 patients treated with EGFR-TKIs were analyzed. ERbeta1 was
      highly expressed, and the strong expression of cytoplasmic ERbeta1 was related to
      a shorter PFS. In conclusion, ERbeta1 was activated in EGFR-TKI secondary
      resistance. The downregulation of ERbeta1 sensitized the cells to EGFR-TKIs.
      ERbeta1 may be a key molecule in EGFR-TKI therapy. In addition, anti-ERbeta1
      treatment may reverse TKI resistance.

PMID- 29328406
TI  - miR-141 inhibits prostatic cancer cell proliferation and migration, and induces
      cell apoptosis via targeting of RUNX1.
AB  - Prostate cancer (PCa) is the most commonly diagnosed male malignancy and the
      second leading cause of male cancer-related deaths. miR-141 has been demonstrated
      to be inversely correlated with tumorigenicity. In the present study, we
      investigated the effect of miR-141 and runt-related transcription factor 1
      (RUNX1) on PCa cells. We determined that miR-141 was expressed at a low level and
      RUNX1 was expressed at a high level in PCa tissues in comparison to that in
      adjacent normal tissues. Upregulation of miR-141 significantly inhibited cell
      growth, migration and invasion, and promoted cell apoptosis in PCa cells.
      Furthermore, miR-141 overexpression suppressed the expression of MMP-2 and MMP-9,
      and increased the expression of FOXO1 and p21. However, overexpression of RUNX1
      could antagonize the effects of miR-141 on PCa cells. Our findings demonstrated
      that miR-141 could suppress cell growth, migration and invasion and induce cell
      apoptosis by targeting RUNX1 in PCa cells. Thus, miR-141/RUNX1 play critical
      roles in the progression of PCa and may be promising targets for the diagnosis
      and treatment of PCa.

PMID- 29328405
TI  - Liraglutide repairs the infarcted heart: The role of the SIRT1/Parkin/mitophagy
      pathway.
AB  - Liraglutide is glucagon-like peptide-1 receptor agonist used for treating
      patients with type 2 diabetes mellitus. The present study aimed to investigate
      the role and mechanism of liraglutide in repairing the infarcted heart following
      myocardial infarction. The results of the present study demonstrated that
      amplification of the dose of liraglutide for ~28 days was able to reduce cardiac
      fibrosis, inflammatory responses and myocardial death in the post-infarcted
      heart. In vitro, liraglutide protected cardiomyocyte mitochondria against the
      chronic hypoxic damage, inhibiting the mitochondrial apoptosis pathways.
      Mechanistically, liraglutide elevated the expression of NAD-dependent protein
      deacetylase sirtuin-1 (SIRT1), which increased the expression of Parkin, leading
      to mitophagy activation. Protective mitophagy reversed cellular adenosine 5'
      triphosphate production, reduced cellular oxidative stress and balanced the redox
      response, sustaining mitochondrial homeostasis. Notably, following blockade of
      glucagon-like peptide 1 receptor or knockdown of Parkin, the beneficial effects
      of liraglutide on mitochondria disappeared. In conclusion, the results of the
      present study illustrated the protective role of liraglutide in repairing the
      infarcted heart via regulation of the SIRT1/Parkin/mitophagy pathway.

PMID- 29328409
TI  - Alpha gene upregulates TFEB expression in renal cell carcinoma with t(6;11)
      translocation, which promotes cell canceration.
AB  - Renal cell carcinoma (RCC) with t(6;11) translocation has been characterized by
      the fusion of the Alpha gene with the TFEB gene. However, the underlying
      molecular mechanisms remain greatly uncharacterized and effective targeted
      therapy has yet to be identified. In this study, we examined the role of the
      Alpha gene in this tumor entity and the function of the fusion gene Alpha-TFEB
      product in vitro and in vivo. Our results revealed that the luciferase activity
      of Alpha1, Alpha2, Alpha3, Alpha4 and Alpha5 significantly increased compared
      with that of the pGL3-Basic group (P<0.01). The luciferase activity also
      increased significantly in the Alpha1, Alpha2 and Alpha5 groups compared with
      that of the normal TFEB gene group (P<0.01). In addition, the luciferase activity
      of Alpha5 was the strongest located in the 643-693 base sequence. The stable
      transfection of Alpha-TFEB into HK-2 and CaKi-2 cells promoted the expression of
      Alpha-TFEB mRNA and TFEB protein. Furthermore, the overexpression of TFEB
      increased cell proliferation and enhanced the cell invasive ability, and
      decreased cell apoptosis in the Alpha-TFEB stably transfected cells in vitro. In
      vivo experiments revealed that the overexpression of TFEB promoted tumorigenicity
      in nude mice, which was consistent with our in vitro results. On the whole, these
      data indicate that the overexpression of TFEB confers a potent oncogenic signal
      and may thus be a novel therapeutic target in RCC with t(6;11) translocation.

PMID- 29328408
TI  - Genistein attenuates di-(2-ethylhexyl) phthalate-induced testicular injuries via
      activation of Nrf2/HO-1 following prepubertal exposure.
AB  - Di-(2-ethylhexyl) phthalate (DEHP) and genistein (GEN) are of the most common
      endocrine disrupting chemicals (EDCs) present in the environment or the diet.
      However, investigation of the effects of acute exposure to these two EDCs during
      prepuberty has been lacking. In this study, DEHP and GEN were administrated to
      prepubertal male Sprague-Dawley rats by gavage from PND22 to PND35 with vehicle
      control, GEN 50 mg/kg body weight (bw)/day, DEHP50, 150 and 450 mg/kg bw/day, and
      combined treatment. Reproductive parameters including testis weight, anogenital
      distance and organ coefficient were evaluated on PND36. Enzyme activity involved
      in the regulation of testicular redox state as well as expression of genes and
      proteins related to anti-oxidative ability and apoptosis were also investigated.
      The results revealed that by PND36, DEHP treatment had significantly decreased
      the testis weight, organ coefficient, testicular anti-oxidative enzyme activities
      and caused tubular vacuolation; however, co-administration of GEN partially
      alleviated DEHP-induced testicular injuries and enhanced testicular anti
      oxidative enzyme activities and upregulated the expression of NF-E2 related
      factor 2 and heme oxygenase-1, which indicated that GEN partially attenuated DEHP
      induced male reproductive system damage through anti-oxidative action following
      acute prepubertal exposure to DEHP. Thus, GEN may have use in attenuating the
      damaging effects of other EDCs that lead to reproductive disorders.

PMID- 29328410
TI  - CLDN5 affects lncRNAs acting as ceRNA dynamics contributing to regulating blood
      brain barrier permeability in tumor brain metastasis.
AB  - The blood-brain barrier (BBB) constitutes an efficient organization of tight
      junctions that limits the delivery of tumor to the brain. The principal tight
      junction protein in BBB is claudin-5 (CLDN5), but its mechanism of action remains
      largely unknown. Long non-coding RNAs (lncRNAs) are aberrantly expressed in many
      cancers, some lncRNAs play key roles in regulating BBB permeability and are
      involved in tumor brain metastasis. In particular, lncRNAs can function as
      competing endogenous RNAs (ceRNAs). Herein, we investigated whether ceRNA
      dysregulation is associated with alterations of the level of CLDN5 in human brain
      vascular endothelial hCMEC/D3 cells. The Affymetrix Human Transcriptome Array 2.0
      and Affymetrix GeneChip miRNA 4.0 Array were used to detect the expression levels
      of 2,578 miRNAs, 22,829 lncRNAs, and 44,699 mRNAs in pLL3.7-CLDN5-transfected and
      pLL3.7 control hCMEC/D3 cells. The distinctly expressed miRNAs, lncRNAs, and
      mRNAs were subjected to construction of miRNA-lncRNA-mRNA interaction network. A
      total of 41 miRNAs, 954 lncRNAs, and 222 mRNAs were found to be differentially
      expressed between the CLDN5-overexpressing and control group. 148 lncRNA acting
      as ceRNAs were identified based on the miRNA-lncRNA-mRNA interaction network. The
      function of differential mRNA in the network was determined by GO and pathway
      analysis. The potential roles of the 27 ceRNAs were revealed, the possible
      biology functions of these regulatory ceRNAs mainly included tight junction,
      focal adhesion, cell-cell adhesion, cell growth and apoptosis. The identified
      sets of miRNAs, lncRNAs and mRNAs specific to CLDN5-overexpressing hCMEC/D3 cells
      were verified by quantitative real-time RT-PCR experiment. Our study predicts the
      biological functions of a multitude of ceRNAs associated with the alteration of
      CLDN5 in brain vascular endothelial cells. Our data suggest that these
      dysregulated ceRNAs, in conjunction with the high CLDN5 levels, could serve as
      useful targets of prevention of brain metastasis formation. Further studies are
      warranted to determine the role of these ceRNAs in facilitating the function of
      CLDN5 in brain-tumor barrier.

PMID- 29328411
TI  - DNA methylation enzyme inhibitor RG108 suppresses the radioresistance of
      esophageal cancer.
AB  - Esophageal cancer (EC) is the eighth most common highly aggressive cancer
      worldwide. The purpose of this study was to investigate the effect of the DNA
      methyltransferase inhibitor RG108 on the radiosensitivity of EC cells. MTT and
      clonogenic assays were performed to assess the effect of RG108 on the
      proliferation and radiosensitivity of Eca-109 and TE-1 human EC cells. The cell
      cycle progression and alterations in apoptosis were analyzed by flow cytometry.
      For the in vivo analysis, the Eca-109 cells were inoculated into nude mice to
      establish tumors. Tissues from xenografts were obtained to detect changes to
      microvessels and tumor growth by immunohistochemistry (IHC). RNA-seq was used to
      identify differentially expressed genes. We found that RG108 increased the
      radiosensitivity of EC cells. Apoptosis and G2/M-phase arrest were induced by X
      ray irradiation and were significantly enhanced by RG108. In addition, growth of
      tumor xenografts from the Eca-109 cells was significantly inhibited by
      irradiation in combination with RG108. The RNA-seq analysis revealed that,
      compared with radiation alone, X-ray irradiation in combination with RG108
      altered the expression of 121 genes in multiple pathways, including the TGF-beta
      signaling pathway and the Epstein-Barr virus infection pathway. In conclusion,
      RG108 induced radiosensitivity in EC cells both in vitro and in vivo.

PMID- 29328412
TI  - Therapeutic efficacy of cyclosporin A against spinal cord injury in rats with
      hyperglycemia.
AB  - The present study aimed to explore the therapeutic effects of cyclosporin A (CsA)
      on spinal cord injury (SCI) in rats with hyperglycemia and to identify a novel
      potential method to treat SCI in the presence of hyperglycemia. Female Sprague
      Dawley (SD) rats were randomly allocated into four groups: Sham, SCI,
      SCI+hyperglycemia and SCI+hyperglycemia+CsA groups. Streptozotocin-induced
      hyperglycemic SD rats and a weight-drop contusion SCI model were established. The
      Basso, Beattie, Bresnahan scale and inclined plane test were used to evaluate the
      neurological function of the rats. Flow cytometric assay was performed to detect
      the apoptotic rates of cells in the spinal cord. ELISA and western blot analysis
      were performed to determine the levels of interleukin (IL)-10, tumor necrosis
      factor (TNF)-alpha, cyclophilin-D (Cyp-D) and apoptosis-inducing factor (AIF).
      The results demonstrated that CsA significantly improved the neurological
      function of the SCI rats with hyperglycemia. CsA markedly reduced the number of
      apoptotic cells exaggerated by hyperglycemia in the spinal cord of the SCI rats.
      CsA significantly decreased the expression levels of IL-10, TNF-alpha, Cyp-D and
      AIF in the spinal cord of the SCI rats. Overall, the present study revealed a
      significant role of CsA in the treatment of SCI in the presence of hyperglycemia
      by inhibiting the apoptosis of spinal cord cells.

PMID- 29328413
TI  - Prevalence of the CYP2C19*2 (681 G>A), *3 (636 G>A) and *17 (-806 C>T) alleles
      among an Iranian population of different ethnicities.
AB  - Polymorphisms in the cytochrome P (CYP) 450 family may cause adverse drug
      responses in individuals. Cytochrome P450 2C19 (CYP2C19) is a member of the CYP
      family, where the presence of the 681 G>A, 636 G>A and 806 C>T polymorphisms
      result in the CYP2C19*2, CYP2C19*3 and CYP2C19*17 alleles, respectively. In the
      current study, the frequency of the CYP2C19*2, CYP2C19*3 and CYP2C19*17 alleles
      in an Iranian population cohort of different ethnicities were examined and then
      compared with previously published frequencies within other populations. Allelic
      and genotypic frequencies of the CYP2C19 alleles (*2, *3 and *17) were detected
      using polymerase chain reaction (PCR)-restriction fragment length polymorphism
      analysis, PCR-single-strand conformation polymorphism analysis and DNA sequencing
      from blood samples of 1,229 unrelated healthy individuals from different
      ethnicities within the Iranian population. The CYP2C19 allele frequencies among
      the Iranian population were 21.4, 1.7, and 27.1% for the CYP2C19*2, CYP2C19*3 and
      CYP2C19*17 alleles, respectively. The frequency of the homozygous A/A variant of
      the CYP2C19*2 allele was significantly high and low in the Lur (P<0.001) and
      Caspian (P<0.001) ethnicities, respectively. However, the frequency of the
      homozygous A/A variant of the CYP2C19*3 allele was not detected in the Iranian
      cohort in the current study. The frequency of the heterozygous G/A variant of the
      CYP2C19*3 allele had the significantly highest and lowest frequency in the Fars
      (P<0.001) and Lur (P<0.001) groups, respectively. The allele frequency of the
      homozygous T/T variant of the CYP2C19*17 allele was significantly high in the
      Caspian (P<0.001) and low in the Kurd (P<0.05) groups. The frequency of the
      CYP2C19 alleles involved in drug metabolism, may improve the clinical
      understanding of the ethnic differences in drug responses, resulting in the
      advancement of the personalized medicine among the different ethnicities within
      the Iranian population.

PMID- 29328414
TI  - MALAT1 enhanced the proliferation of human osteoblasts treated with ultra-high
      molecular weight polyethylene by targeting VEGF via miR-22-5p.
AB  - Osteolysis associated with an implanted prosthesis is the major cause of failure
      in prosthesis implantation, and a severe public health issue worldwide. The type
      of bone metabolism associated with this disorder has been a major focus for
      improving the outcomes of patients with osteolysis. The role of metastasis
      associated lung adenocarcinoma transcript 1 (MALAT1; a member of the long coding
      RNA family) during the onset of osteolysis and the related molecular regulatory
      mechanism in ultra-high molecular weight polyethylene (UHMWPE)-treated hFOB 1.19
      cells were investigated in the current study. The effect of MALAT1 knockdown on
      cell viability, cell apoptosis and osteolysis-associated signaling were also
      examined, and the interactions that occurred between MALAT1 and an anti
      osteolysis molecule, microRNA (miR)-22-5p were investigated. Additionally,
      knockdown of vascular endothelial growth factor (VEGF) exerted similar biological
      effects as observed following miR-22-5p overexpression. The data showed that
      MALAT1 and pro-osteolysis indicators, receptor activator of nuclear factor-kappaB
      ligand (RANKL) and VEGF were upregulated in clinical interface membrane samples.
      Knockdown of MALAT1 inhibited the growth of UHMWPE-treated hFOB 1.19 cells, and
      this effect was associated with the upregulation of OPG, and downregulation of
      RANKL and VEGF. Results of a dual luciferase assay confirmed the interaction
      between VEGF and miR-22-5p, and also between MALAT1 and miR-22-5p. Additionally,
      subsequent assays indicated that overexpression of MALAT1 suppressed the anti
      osteolysis effect of miR-22-5p, which would further induce VEGF expression. The
      data indicated that MALAT1 has an in port ant role in the onset of osteolysis via
      its ability to induce RANKL expression and inhibit the effect of miR-22-5p.

PMID- 29328416
TI  - Endotoxin tolerance induced by lipopolysaccharide preconditioning protects
      against surgery-induced cognitive impairment in aging mice.
AB  - Postoperative cognitive dysfunction (POCD) is a clinical syndrome characterized
      by varying degrees of cognitive functional decline in patients following major
      surgery. Inflammation and a dysregulated innate immune system exert broad effects
      in the periphery and central nervous system, yet the mechanisms underlying POCD
      remain poorly understood and without effective therapy. It has been reported that
      modulation of the dysregulated inflammatory response with low-dose
      lipopolysaccharide (LPS) preconditioning, a phenomenon additionally referred to
      as endotoxin tolerance, has the potential to reduce neuroinflammation, blood
      brain barrier disruption, and cognitive impairment in a number of disease states.
      Therefore, it was hypothesized that endotoxin tolerance induced by LPS
      preconditioning may protect against surgery-induced cognitive impairment in aging
      mice. Using a mouse model of surgery-induced cognitive decline, the present study
      demonstrated that exploratory laparotomy caused a significant impairment in
      hippocampal-dependent memory. Notably, one application of low-dose LPS
      preconditioning at 24 h prior to surgery improved the cognitive impairment and
      abolished the signs of neuroinflammation in the hippocampus following surgery.
      However, LPS injection at 6 h or immediately prior to surgery did not confer such
      beneficial effects, suggesting that the effects of LPS-induced endotoxin
      tolerance may depend on the time of application. In conclusion, the results of
      the present study suggested that low-dose LPS preconditioning may markedly
      alleviate surgery-induced neuroinflammation and cognitive impairment in aging
      mice, which may provide a novel approach to preventing POCD and, potentially,
      other forms of memory impairment.

PMID- 29328415
TI  - Role of catalpol in ameliorating the pathogenesis of experimental autoimmune
      encephalomyelitis by increasing the level of noradrenaline in the locus
      coeruleus.
AB  - The endogenous neurotransmitter, noradrenaline, exerts anti-inflammatory and
      neuroprotective effects in vivo and in vitro. Reduced noradrenaline levels
      results in increased inflammation and neuronal damage. The primary source of
      noradrenaline in the central nervous system is tyrosine hydroxylase (TH)-positive
      neurons, located in the locus coeruleus (LC). TH is the rate-limiting enzyme for
      noradrenaline synthesis; therefore, regulation of TH protein expression and
      intrinsic enzyme activity represents the central means for controlling the
      synthesis of noradrenaline. Catalpol is an iridoid glycoside purified from
      Rehmannia glutinosa Libosch, which exerts a neuroprotective effect in multiple
      sclerosis (MS). The present study used an experimental mouse model of autoimmune
      encephalomyelitis to verify the neuroprotective effects of catalpol. Significant
      improvements in the clinical scores were observed in catalpol-treated mice.
      Furthermore, catalpol increased TH expression and increased noradrenaline levels
      in the spinal cord. In primary cultures, catalpol exerted a neuroprotective
      effect in rat LC neurons by increasing the noradrenaline output. These results
      suggested that drugs targeting LC survival and function, including catalpol, may
      be able to benefit patients with MS.

PMID- 29328417
TI  - MicroRNA-129-5p suppresses cell proliferation, migration and invasion via
      targeting ROCK1 in osteosarcoma.
AB  - Osteosarcoma (OS) is the most common primary malignancy of the bone in teenagers
      and accounts for 20-35% of all malignant primary bone tumors. Increasing evidence
      shows that microRNAs (miRNAs) are abnormally expressed in several types of human
      cancer. miRNAs are necessary to maintain the malignant phenotype of cancer cells
      and can function as either tumor suppressors or oncogenes. The present study
      aimed to measure the expression of miRNA-129-5p (miR-129-5p) in OS, determine the
      effects of miR-129-5p on the malignant behaviors of OS cells, and elucidate the
      molecular mechanism underlying the oncogenesis and progression of OS. The
      expression levels of miR-129-5p in OS tissues and cell lines were measured using
      reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis.
      SAOS-2 and U2OS cells were then transfected with miR-129-5p mimics or miR
      negative control. The effects of miR-129-5p on the proliferation, migration and
      invasion of SAOS-2 and U2OS cells in vitro were then evaluated using 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, Transwell migration assay
      and invasion assays, respectively. In addition, bioinformatics analysis, a
      luciferase reporter assay, and RT-qPCR and western blot analyses were used to
      examine whether Rho-associated protein kinase 1 (ROCK1) was a direct target of
      miR-129-5p. The mRNA expression of ROCK1 in OS tissues was detected using RT-qPCR
      analysis, and the biological roles of ROCK1 in OS cells were also evaluated. The
      results showed that miR-129-5p was significantly downregulated in the OS tissues
      and cell lines. The re-expression of miR-129-5p suppressed the cell
      proliferation, migration and invasion of OS cells. In addition, ROCK1 was
      confirmed as a direct target of miR-129-5p. The mRNA expression of ROCK1 was high
      in OS tissues and inversely correlated with the expression of miR-129-5p. The
      downregulation of ROCK1 inhibited the proliferation, migration and invasion of OS
      cells. These findings suggested that miR-129-5p inhibited cell proliferation,
      migration and invasion in the development of OS via the negative regulation of
      ROCK1. The miR-129-5p/ROCK1 axis may serve as an efficient target in cancer
      therapy.

PMID- 29328418
TI  - microRNA-3941 targets IGF2 to control LPS-induced acute pneumonia in A549 cells.
AB  - The present study aimed to investigate the potential roles and regulatory
      mechanism of microRNA (miR)-3941 in lipopolysaccharides (LPS)-induced acute
      pneumonia. The expression of miR-3941 in child patients with acute pneumonia was
      detected and A549 cells were treated with LPS to establish the cellular model of
      acute pneumonia. The effects of miR-3941 in LPS-induced cell injury were
      investigated by assessing cell viability, apoptosis and inflammation. In
      addition, the regulatory relationship between miR-3941 and insulin-like growth
      factor 2 (IGF2) was explored, as well as the association between miR-3941 and the
      phosphatidylinositol-4,5-bisphosphate 3-kinase/protein kinase B (PI3K/AKT)
      pathway. miR-3941 was significantly down-regulated in patients with acute
      pneumonia (P<0.01). In the cell model of acute pneumonia, LPS treatment
      significantly induced cell injury via inhibiting cell viability (P<0.05 or
      P<0.01), inducing cell apoptosis (P<0.01) and enhancing the production of
      cytokines [interleukin (IL)-6, IL-8 and tumor necrosis factor-alpha; P<0.01 or
      P<0.001]. LPS treatment also resulted in a significantly decreased expression of
      miR-3941 in A549 cells (P<0.01) and the overexpression of miR-3941 significantly
      alleviated LPS-induced cell injury (P<0.05). In addition, IGF2 was confirmed as a
      direct target gene of miR-3941. Knockdown of IGF2 significantly alleviated LPS
      induced cell injury (P<0.05, P<0.01 or P<0.001), which was significantly reversed
      by suppression of miR-3941 (P<0.05, P<0.01 or P<0.001). Furthermore, inhibition
      of miR-3941 was demonstrated to activate the PI3K/AKT pathway, which was
      inhibited following knockdown of IGF2. The present study indicates that miR-3941
      is downregulated in child patients with acute pneumonia and that downregulation
      of miR-3941 may promote LPS-induced cell injury in A549 cells via targeting IGF2
      to regulate the activation of the PI3K/AKT pathway. Therefore, miR-3941 may be a
      potential therapeutic target for the treatment of acute pneumonia in child
      patients.

PMID- 29328419
TI  - Screening and clinical evaluation of dominant peptides of centromere protein F
      antigen for early diagnosis of hepatocellular carcinoma.
AB  - Tumor-associated antigens, such as centromere protein F (CENP-F), have been
      recognized as potential serological biomarkers for early diagnosis of
      hepatocellular carcinoma (HCC); however, the exact regions corresponding to the
      dominant peptides of CENP-F antigen remain to be explored. We aimed to screen and
      evaluate potential dominant peptides of CENP-F for early diagnosis of HCC.
      Dominant peptides of CENP-F were predicted by BioSun version 3.0, and the
      corresponding recombinant proteins were prepared. Enzyme-linked immunosorbent
      assays were conducted for initial screening of dominant peptides, and selected
      dominant peptides were subjected to further clinical evaluation. Eight dominant
      peptides of CENP-F antigens were predicted at amino acids (a.a) 121-220, 335-416,
      1100-1265, 1670-1791, 1759-2093, 2075-2210, 2485-2592, and 2808-2960. Initial
      screening of the predicted peptides in samples of 47 HCC cases showed the highest
      diagnostic value for 121-220 a.a and 1670-1791 a.a peptides with area under the
      curve (AUC) values of 0.795 [95% confidence interval (CI), 0.706-0.884] and 0.809
      (95% CI, 0.721-0.896), sensitivity of 58.3 and 85.4%, and specificity of 93.9 and
      65.3%, respectively. Further evaluation of the two peptides in 405 samples
      comprised of 153 HCC, 126 liver cirrhosis and 126 healthy controls, presenting an
      AUC of 0.743 (95% CI, 0.674-0.812) for 121-220 a.a peptide in detecting early
      stage HCCs. Specifically, the 121-220 a.a peptide showed a complementary effect
      in combination with alpha-fetoprotein (AFP) for the detection of early-stage HCC
      with increased AUC value of 0.840 (95% CI, 0.781-0.899), and sensitivity of 81.4%
      and specificity of 72.2%. In conclusion, our study identified the 121-220 a.a
      dominant peptide as the region of CENP-F antigen with the highest immunogenicity
      and demonstrated its value in combination with AFP for diagnosis of early-stage
      HCC.

PMID- 29328422
TI  - L-mimosine induces caspase-9-mediated apoptosis in human osteosarcoma cells.
AB  - L-mimosine is a rare plant amino acid extracted from Mimosa or Leucaena spp., and
      it has been reported to exhibit antitumor activity in a number of types of
      cancer. However, the underlying mechanisms remain to be clarified. In the present
      study, the effect of L-mimosine was investigated in human osteosarcoma cells. A
      Cell Counting Kit-8 assay and flow cytometry were used for toxicity detection.
      Hoechst staining and transmission electron microscopy (TEM), in addition to
      western blot analysis, were used for the examination of the associated
      mechanisms. The results of the present study indicated that L-mimosine
      significantly inhibited cell proliferation by inducing cellular apoptosis in
      osteosarcoma cells. The Hoechst staining results and TEM revealed that nuclear
      damage increased with the concentration increase in L-mimosine, as did the
      formation of apoptotic bodies. Additionally, the results of the western blot
      analysis confirmed that the treatment of cells with L-mimosine was accompanied by
      increasing expression of cleaved caspase-9. L-mimosine-induced apoptosis was
      inhibited by the caspase-9 inhibitor Z-LEHD-FMK. In addition, the extracellular
      signal-regulated kinase (ERK) signaling pathway was suppressed following
      treatment with L-mimosine. In conclusion, the results of the present study
      suggested that L-mimosine induced apoptosis via the mitochondrial apoptotic
      pathway. The ERK signaling pathway was indicated to be an additional mechanism
      underlying apoptosis induction. The results provided evidence for the use of L
      mimosine as a promising candidate for osteosarcoma therapy.

PMID- 29328420
TI  - Ginsenoside Rg3 inhibits keloid fibroblast proliferation, angiogenesis and
      collagen synthesis in vitro via the TGF-beta/Smad and ERK signaling pathways.
AB  - A wide range of therapeutic options exists for the treatment of keloids, all of
      which have their own strengths; however, a high risk of side-effects and frequent
      recurrence remains. Therefore, the present study aimed to identify improved
      therapeutic approaches or drugs for the treatment of keloids. Ginsenoside Rg3
      (Rg3) has been reported to exert numerous antitumor effects, thus indicating that
      Rg3 may be a potential therapeutic agent that targets keloids. The present study
      determined the effects of Rg3 on human keloid fibroblasts (KFs) in vitro, and
      further explored the associated molecular and cellular mechanisms. Keloid scar
      specimens were obtained from patients, aged between 22 and 35 years, without
      systemic diseases and primary cells were isolated from keloid tissues. In each
      assay, KFs were divided into three groups and were cultured in medium with or
      without various concentrations of Rg3 (50 or 100 ug/ml). Cell viability assay,
      flow cytometry, quantitative polymerase chain reaction, cell migration assay,
      immunofluorescence staining, western blot analysis, Transwell cell invasion assay
      and immunohistochemical analysis were used to analyze the KFs and keloid explant
      cultures. The results of the present study demonstrated that Rg3 was able to
      exert an inhibitory effect on the transforming growth factor-beta/Smad and
      extracellular signal-regulated kinase signaling pathways in KFs. The
      proliferation, migration, invasion, angiogenesis and collagen synthesis of KFs
      were markedly suppressed following treatment with Rg3. Furthermore, the results
      of an ex vivo assay indicated that Rg3 inhibited angiogenesis and reduced
      collagen accumulation in keloids. Significant statistical differences existed
      between the control and Rg3-treated groups (P<0.05). All of these experimental
      results suggested that Rg3 may serve as a reliable drug for the treatment of
      patients with keloids.

PMID- 29328421
TI  - Antitumor activity of curcumin by modulation of apoptosis and autophagy in human
      lung cancer A549 cells through inhibiting PI3K/Akt/mTOR pathway.
AB  - Curcumin is known to exhibit anticancer effects on various cancers with selective
      cytotoxicity in tumor cells. In the present study, the effects of curcumin
      induced multiple PCDs on human non-small cell lung cancer (NSCLC) cells and the
      potential molecular mechanisms of apoptosis and autophagy triggered by curcumin
      via the PI3K/Akt/mTOR signaling pathway were explored, further confirmed by co
      culture of curcumin with mTOR blocker rapamycin and PI3K/Akt inhibitor LY294002.
      The anti-proliferation effect of different stimulus was measured by MTT assay.
      Apoptosis was detected by flow cytometry. Autophagy induction was detected by MDC
      labeling and western blotting of Beclin1, LC3, and p62 expression. The mRNA and
      protein expression levels of Akt and mTOR were assayed by real-time fluorescence
      quantitative (qRT-PCR) technique and western blotting. Our results showed that
      curcumin inhibited the viability of A549 cells time- and dose-dependently. In
      addition, a dosage-dependent A549 cell apoptosis-induction phenomena was observed
      by the curcumin intervention. Moreover, obvious autophagy was induced after
      curcumin-treatment, characterized by the formation of fluorescent particles
      [autophagic vesicles (AVs)] and significant increase in ratio of LC3-II/LC3-I and
      Beclin1 as well as decreased p62 expression. Furthermore, the effect of curcumin
      on a substantial downregulation of phosphatidylinositol 3-kinase
      (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway was observed. It is worth
      noting that the inhibition of mTOR by rapamycin or of PI3K/Akt by LY294002
      augmented curcumin-induced apoptosis and autophagy, leading to significant
      inhibition of cell proliferation. From these findings, it can be speculated that
      curcumin potently inhibit the cell growth of NSCLC A549 cells through inducing
      both apoptosis and autophagy by inhibition of the PI3K/Akt/mTOR pathway. These
      results support the potential use of curcumin as a novel candidate in treatment
      of human lung cancer.

PMID- 29328423
TI  - Cetuximab enhances cisplatin-induced endoplasmic reticulum stress-associated
      apoptosis in laryngeal squamous cell carcinoma cells by inhibiting expression of
      TXNDC5.
AB  - Cisplatin and cetuximab, an anti-epidermal growth factor receptor (EGFR)
      monoclonal humanized antibody, have been used for treatment of laryngeal squamous
      cell carcinoma (LSCC). It has been demonstrated that cisplatin and inhibition of
      EGFR signaling may induce endoplasmic reticulum (ER) stress-associated apoptosis.
      However, ER protein thioredoxin domain-containing protein 5 (TXNDC5) reportedly
      protects cells from ER stress-associated apoptosis. The present study
      investigated the interaction between cisplatin, cetuximab and TXNDC5 on ER stress
      associated apoptosis in LSCC cells. AMC-HN-8 human LSCC cells with or without
      TXNDC5 overexpression or knockdown were treated with cisplatin (5, 10, 20 and 40
      uM) and/or cetuximab (10, 50, 100 and 150 ug/ml), for 12, 24, 36 and 48 h.
      Cisplatin and cetuximab concentration- and time-dependently increased and
      decreased the expression of TXNDC5 in AMC-HN-8 cells, respectively. Knockdown of
      TXNDC5 markedly augmented cisplatin-induced levels of CCAAT/enhancer-binding
      protein homologous protein (CHOP), caspase-3 activity and apoptosis; while
      overexpression of TXNDC5 largely eliminated cetuximab-induced levels of CHOP,
      caspase-3 activity and apoptosis. Cisplatin and cetuximab demonstrated a
      combinatorial effect on increasing the levels of CHOP, caspase-3 activity and
      apoptosis, which was largely eliminated by overexpression of TXNDC5 or a reactive
      oxygen species (ROS) scavenger/antagonist. In addition, promoter/luciferase
      reporter assays revealed that cisplatin and cetuximab regulated the expression of
      TXNDC5 at the gene transcription/promoter level. In conclusion, the findings
      suggested that ER stress-associated apoptosis is a major mechanism underlying the
      apoptotic effect of cisplatin and cetuximab on LSCC cells; cetuximab enhanced
      cisplatin-induced ER stress-associated apoptosis in LSCC cells largely by
      inhibiting the expression of TXNDC5 and thereby increasing ROS production;
      cisplatin and cetuximab had stimulatory and inhibitory effects on the TXNDC5 gene
      promoter, respectively. The present study offered novel insights into the
      pharmacological effects of cisplatin and cetuximab on LSCC. It also suggested
      that TXNDC5 may be a potential therapeutic target for LSCC.

PMID- 29328424
TI  - Vitexin induces G2/M-phase arrest and apoptosis via Akt/mTOR signaling pathway in
      human glioblastoma cells.
AB  - Glioblastoma is a common primary brain tumor with aggressive malignancy, which
      results in poor outcomes, short survival time and high mortality. Vitexin, an
      active ingredient from natural products, has been reported to inhibit cell growth
      and induce cell apoptosis in various cancer cell lines including hepatocellular
      carcinoma, oral and esophageal cancer. To the best of the authors knowledge, the
      present study was the first to investigate anticancer effects of vitexin on human
      glioblastoma cells and potential underlying mechanisms. The present study
      demonstrated that vitexin inhibited cell viability in a dose- and time-dependent
      manner. In the present study, vitexin induced G2/M cell cycle arrest, as
      demonstrated by flow cytometry. Induction of cell apoptosis following vitexin
      treatment, was further indicated by observation of morphological alterations,
      flow cytometry analysis and detection of cleaved-poly (ADP-ribose) polymerase.
      The present study also demonstrated that vitexin inhibited RAC-alpha
      serine/threonine-protein kinase (Akt)/mechanistic target of rapamycin kinase
      (mTOR) signaling in human glioblastoma cells. Collectively, the results of the
      present study demonstrated that vitexin induced G2/M cell cycle arrest and
      apoptosis by inhibiting Akt/mTOR signaling in human glioblastoma cells. Vitexin
      may in the future be used as a therapeutic agent for treatment of malignant
      glioblastoma.

PMID- 29328425
TI  - Bioinformatics analysis of the CDK2 functions in neuroblastoma.
AB  - The present study aimed to elucidate the potential mechanism of cyclin-dependent
      kinase 2 (CDK2) in neuroblastoma progression and to identify the candidate genes
      associated with neuroblastoma with CDK2 silencing. The microarray data of
      GSE16480 were obtained from the gene expression omnibus database. This dataset
      contained 15 samples: Neuroblastoma cell line IMR32 transfected with CDK2 shRNA
      at 0, 8, 24, 48 and 72 h (n=3 per group; total=15). Significant clusters
      associated with differentially expressed genes (DEGs) were identified using fuzzy
      C-Means algorithm in the Mfuzz package. Gene ontology and pathway enrichment
      analysis of DEGs in each cluster were performed, and a protein-protein
      interaction (PPI) network was constructed. Additionally, functional annotation of
      DEGs in clusters was performed for the detection of transcription factors and
      tumor-associated genes. A total of 4 clusters with significant change tendency
      and 1,683 DEGs were identified. The hub nodes of the PPI network constructed by
      DEGs in Cluster 1, Cluster 2, Cluster 3 and Cluster 4 were MDM2 oncogene, E3
      ubiquitin protein ligase (MDM2), cyclin-dependent kinase 1 (CDK1), proteasome
      (prosome, macropain) 26S subunit, non-ATPase, 14 (PSMD14) and translocator
      protein (18 kDa) (TSPO) respectively. These genes were significantly enriched in
      the p53 signaling pathway, cell cycle, proteasome and systemic lupus
      erythematosus pathways. MDM2, CDK1, PSMD14 and TSPO may be key target genes of
      CDK2. CDK2 may have key functions in neuroblastoma progression by regulating the
      expression of these genes.

PMID- 29328426
TI  - Relaxant and vasoprotective effects of ginger extracts on porcine coronary
      arteries.
AB  - Ginger (Zingiber officinale Roscoe) is a popular Chinese herbal medicine, which
      is considered to warm the stomach and dispel cold in traditional Chinese
      medicine. Ginger is widely used to treat stomach disorders, and it has been
      reported to exhibit antithrombotic activity via the inhibition of platelet
      aggregation and thromboxane B2 production in vitro. Cardiovascular disease is
      associated with the aberrant functioning of the heart and circulatory system; the
      relatively narrow vessels of the circulation are commonly affected and blocked by
      atherosclerosis, which may result in angina or heart attack. Numerous drugs and
      medicines are used to treat myocardial infarction; however, they are often
      associated with numerous side effects. Therefore, it is important to identify
      substitutive drugs with no unbearable side effects. In the present study, the
      relaxant effects of ginger crude extract (GCE) were determined on porcine
      coronary arteries. The DPPH radical scavenging assay, lucigenin-enhanced
      chemiluminescence assay and western blot analysis were used to individually
      detect antioxidant assay of ginger extraction or superoxide anion produced by
      endothelial cells and molecular signaling. The results indicated that GCE induced
      relaxation of porcine coronary arteries in an endothelium-dependent manner. GCE
      increased vasoprotection via the suppression of nitric oxide synthase and
      cyclooxygenase. In addition, GCE possessed antioxidant ability, as determined
      using 1,1-diphenyl-2-picrylhydrazyl and lucigenin-enhanced chemiluminescence
      assays. Taken together, the present study demonstrated that GCE exerts marked
      vasoprotective effects and free radical-scavenging activities in porcine coronary
      arteries.

PMID- 29328427
TI  - miR-133b reverses cisplatin resistance by targeting GSTP1 in cisplatin-resistant
      lung cancer cells.
AB  - MicroRNAs play a critical role in chemoresistance and are implicated in various
      biological and pathological processes of cells. The objective of the present
      study was to explore the role of miR-133b and its mechanism in the regulation of
      cisplatin resistance and tumor progression in cisplatin-resistant non-small cell
      lung cancer (NSCLC) cells. Reverse transcription-quantitative polymerase chain
      reaction and western blot assays of the cisplatin-resistant cell lines A549/DPP
      and H1299/DDP displayed the reduced expression of miR-133b and increased
      expression of glutathione-S-transferase P1 (GSTP1) in the resistant cells
      compared with the respective parental cell lines A549 and H1299. Cell Counting
      kit-8, flow cytometry, colony formation and Transwell migration assays indicated
      that the overexpression of miR-133b increased the chemosensitivity to cisplatin
      and attenuated the proliferation and migration capacities of the cisplatin
      resistant NSCLC cell lines in vitro. A dual-luciferase reporter assay
      demonstrated that miR-133b negatively regulated the expression of GSTP1 by
      targeting its 3'-untranslated region. In addition, the knockdown of GSTP1 by
      transfection with small interfering RNA exerted similar effects on cell
      chemosensitivity, proliferation and migration as did ectopic miR-133b expression,
      in addition to the upregulation of Bax and downregulation of Bcl-2, survivin and
      matrix metalloproteinase expression. In conclusion, the present study findings
      provide the insights that miR-133b reduces cisplatin resistance and its
      overexpression contributes to the suppression of the malignant growth and
      aggressiveness of cisplatin-resistant NSCLC cells by targeting GSTP1. This could
      potentially be exploited as a novel therapeutic strategy for the reversal of
      cisplatin resistance.

PMID- 29328428
TI  - Regulation of drug resistance and metastasis of gastric cancer cells via the
      microRNA647-ANK2 axis.
AB  - Due to a lack of effective methods for early diagnosis, the majority of patients
      with gastric cancer (GC) are diagnosed during the late stages of the disease,
      which are often accompanied by metastasis. For these patients, despite being
      considered an important therapeutic modality in the treatment of cancer,
      chemotherapy is usually not effective due to multidrug resistance (MDR). The
      expression levels of MDR/metastasis-associated genes are regulated by numerous
      microRNAs (miRNAs/miRs). The expression of miR-647 in GC tissues and SGC7901/VCR
      cell line (drug resistance to vincristine) was detected by qRT-PCR. The effect of
      overexpression of miR-647 on drug resistance was evaluated by measuring the half
      maximal inhibitory concentration (IC50) value of SGC-7901/VCR to vincristine and
      tumor growth in vivo. Moreover, drug-induced cell apoptosis and cell cycle were
      evaluated by flow cytometry, as well as the ability of cell migration and
      invasiveness detected by wound healing and transwell assay. Furthermore,
      underlying targets of miR-647 were predicted by TargetScan and MicroRNA;
      meanwhile, the expression of ANK2, FAK, MMP2, MMP12,CD44,SNAIL1 were observed by
      qRT-PCR and western blot analysis. The present study established that the
      expression levels of miR-647 were downregulated in GC tissues from patients with
      metastasis and in the vincristine-resistant SGC7901 (SGC-7901/VCR) GC cell line.
      The IC50 value for vincristine was significantly decreased, whereas the
      proportion of cells in G0/G1 phase and the drug-induced apoptotic rate were
      significantly increased following upregulation of miR-647. Furthermore, the
      results demonstrated that miR-647 overexpression led to decreased migration and
      invasion of SGC-7901/VCR cells. Overexpression of miR-647 was also demonstrated
      to sensitize tumors to chemotherapy in vivo. In addition, miR-647 overexpression
      was able to reduce the expression levels of ankyrin-B, focal adhesion kinase,
      matrix metalloproteinase (MMP)2, MMP12, cluster of differentiation 44 and snail
      family transcriptional repressor 1. In conclusion, these findings demonstrated
      that miR-647 may function as a novel target to ameliorate drug resistance and
      metastasis of GC cells.

PMID- 29328429
TI  - Anthocyanins inhibit high glucose-induced renal tubular cell apoptosis caused by
      oxidative stress in db/db mice.
AB  - Oxidative stress is an important contributory factor resulting the development of
      kidney injury in patients with diabetes. Numerous in vitro and in vivo studies
      have suggested that anthocyanins, natural phenols commonly existing in numerous
      fruits and vegetables, exhibit important antioxidative, anti-inflammatory and
      antihyperlipidemic effects; however, their effects and underlying mechanisms on
      diabetic nephropathy (DN) have not yet been fully determined. In the present
      study, the regulation of apoptosis metabolism and antioxidative effects exhibited
      by anthocyanins [grape seed procyanidin (GSPE) and cyanidin-3-O-beta-glucoside
      chloride (C3G)] were investigated, and the molecular mechanism underlying this
      process was investigated in vivo and in vitro. GSPE administration was revealed
      to suppress renal cell apoptosis, as well as suppress the expression of Bcl-2 in
      diabetic mouse kidneys. Furthermore, GSPE administration was demonstrated to
      suppress the expression of thioredoxin interacting protein (TXNIP), in addition
      to enhancing p38 mitogen-activation protein kinase (MAPK) and extracellular
      signal-regulated kinase 1/2 (ERK1/2) oxidase activity in diabetic mouse kidneys.
      In vitro experiments using HK-2 cells revealed that C3G suppressed the generation
      of HG-mediated reactive oxygen species, cellular apoptosis, the expression of
      cleaved caspase-3 and the Bax/Bcl-2 ratio; and enhanced the expression of
      cytochrome c released from mitochondria. Furthermore, treatment with C3G was
      revealed to suppress the expression of TXNIP, in addition to the phosphorylation
      of p38 MAPK and ERK1/2 oxidase activity in HK-2 cells under HG conditions. In
      addition, treatment with C3G was revealed to attenuate the HG-induced suppression
      of the biological activity of thioredoxin, and to enhance the expression of
      thioredoxin 2 in HK-2 cells under HG conditions. In conclusion, the present study
      demonstrated that anthocyanins may exhibit protective effects against HG-induced
      renal injury in DN via antioxidant activity.

PMID- 29328432
TI  - A double-edged function of DDX3, as an oncogene or tumor suppressor, in cancer
      progression (Review).
AB  - DEAD-box RNA helicase 3 (DDX3) is a highly conserved family member of DEAD-box
      proteins in all eukaryotes from yeasts to human beings. Accumulating studies have
      confirmed DDX3 has the ability to regulate different steps of RNA metabolism,
      including RNA splicing, RNA export, transcription and translation initiation.
      Moreover, DDX3 is involved in many biological processes, such as stress response,
      cell apoptosis, cell cycle regulation and virus infection. In recent years, DDX3
      is getting increasing attention due to its essential roles in cancer progression.
      However, DDX3 role in cancer development is rather complicated. This review
      mainly focuses on the dual roles of DDX3 and DDX3-mediated signaling pathways in
      multiple cancers. In addition, the interplaying causes for the controversial
      roles of DDX3 in cancer are discussed. So far several small molecular chemical
      compounds targeting DDX3 are also summarized from the anticancer activity to the
      clinical trials of DDX3 inhibitors.

PMID- 29328430
TI  - Vanillin improves scopolamine-induced memory impairment through restoration of
      ID1 expression in the mouse hippocampus.
AB  - 4-Hydroxy-3-methoxybenzaldehyde (vanillin), contained in a number of species of
      plant, has been reported to display beneficial effects against brain injuries. In
      the present study, the impact of vanillin on scopolamine-induced alterations in
      cognition and the expression of DNA binding protein inhibitor ID-1 (ID1), one of
      the inhibitors of DNA binding/differentiation proteins that regulate gene
      transcription, in the mouse hippocampus. Mice were treated with 1 mg/kg
      scopolamine with or without 40 mg/kg vanillin once daily for 4 weeks. Scopolamine
      induced cognitive impairment was observed from 1 week and was deemed to be severe
      4 weeks following the administration of scopolamine. However, treatment with
      vanillin in scopolamine-treated mice markedly attenuated cognitive impairment 4
      weeks following treatment with scopolamine. ID1-immunoreactive cells were
      revealed in the hippocampus of vehicle-treated mice, and were hardly detected 4
      weeks following treatment with scopolamine. However, treatment with vanillin in
      scopolamine-treated mice markedly restored ID1-immunoreactive cells and
      expression 4 weeks subsequent to treatment. The results of the present study
      suggested that vanillin may be beneficial for cognitive impairment, by preventing
      the reduction of ID1 expression which may be associated with cognitive
      impairment.

PMID- 29328431
TI  - Bioinformatic analysis of gene expression profiling of intracranial aneurysm.
AB  - Intracranial aneurysm (IA) is a severe clinical condition of primary concern and
      currently, there is no effective therapeutic reagent. The present study aimed to
      investigate the molecular mechanism of IA via bioinformatic analysis. Various
      gene expression profiles (GSE26969) were downloaded from the Gene Expression
      Omnibus database, including 3 IA and 3 normal superficial temporal artery
      samples. Firstly, the limma package in R language was used to identify
      differentially expressed genes (DEGs; P-value <0.01 and |log2 FC|>=1). Secondly,
      the database for annotation, visualization and integrated discovery software was
      utilized to perform pathway and functional enrichment analyses (false discovery
      rate <=0.05). Finally, protein-protein interaction (PPI) network and sub-network
      clustering analyses were performed using the biomolecular interaction network
      database and ClusterONE software, respectively. Following this, a transcription
      factor regulatory network was identified from the PPI network. A total of 1,124
      DEGs were identified, of which 989 were upregulated and 135 downregulated.
      Pathway and functional enrichment analyses revealed that the DEGs primarily
      participated in RNA splicing, functioning of the spliceosome, RNA processing and
      the mRNA metabolic process. Following PPI network analysis, 1 hepatocyte nuclear
      factor (HNF) 4A (transcription factor)-centered regulatory network and 5 DEG
      centered sub-networks were identified. On analysis of the transcription factor
      regulatory network, 6 transcription factors (HNF6, HNF4A, E2F4, YY1, H4 and H31T)
      and a regulatory pathway (HNF6-HNF4-E2F4) were identified. The results of the
      present study suggest that activating transcription factor-5, Jun proto-oncogene,
      activator protein-1 transcription factor subunit, HNF6, HNF4 and E2F4 may
      participate in IA progression via vascular smooth muscle cell apoptosis,
      inflammation, vessel wall remodeling and damage and the tumor necrosis factor
      beta signaling pathway. However, further experimental studies are required to
      validate these predictions.

PMID- 29328433
TI  - Peiminine serves as an adriamycin chemosensitizer in gastric cancer by modulating
      the EGFR/FAK pathway.
AB  - Gastric cancer (GC) is one of the most common malignancies of the digestive
      tract. Adriamycin (ADR) has been widely utilized in various chemotherapy regimens
      for treating GC, yet its long-term application may increase drug resistance
      resulting in treatment failure. Increasing evidence shows that bioactive natural
      products can be used as chemotherapeutic sensitizers that can significantly
      improve chemotherapy sensitivity. Peiminine (PMI) is a biologically active
      component extracted from Fritillaria walujewii Regel. Thus, in the present study,
      we aimed to investigate whether peiminine (PMI) alters the chemosensitivity of GC
      to adriamycin (ADR). GC cells were treated with ADR with or without PMI. MTT
      assay, flow cytometry and a nude mouse tumor xenograft model of SGC7901 cells
      were used to evaluate the chemosensitization activity of PMI combined with ADR.
      Western blotting was used to examine the expression of cyclin D1 and cleaved
      PARP. The RayBio(r) Human RTK phosphorylation antibody array kit was used to test
      the differential protein expression. Compared with the ADR group, PMI combined
      with ADR significantly suppressed cell proliferation and induced cell apoptosis
      in vitro. The growth curve and tumor weight of the tumor xenografts were
      significantly decreased in mice treated with the combination of PMI and ADR.
      However, the organs showed no obvious abnormality after treatment with PMI plus
      ADR. The expression of cyclin D1 was decreased and the level of cleaved PARP was
      increased after treatment with PMI and ADR. The expression of p-EGFR and p-FAK
      was downregulated in cells treated with PMI and ADR, and the validation of p-EGFR
      and p-FAK was in accordance with the result of the phosphorylation antibody array
      kit. PMI may serve as a new chemosensitizer by inhibiting the proliferation and
      inducing the apoptosis to enhance the chemotherapeutic drug sensitivity of ADR in
      GC.

PMID- 29328434
TI  - Chemical conversion of human lung fibroblasts into neuronal cells.
AB  - It has been previously reported that human embryonic fibroblasts and mouse
      embryonic fibroblasts can be converted into neuronal cells using chemical agents,
      along with forced expression specific transcriptional factors. However, the
      materials required for reprogramming in these approaches presents major technical
      difficulties and safety concerns. The current study investigated whether a
      cocktail of small molecules can convert human lung fibroblast cells into neurons.
      The small molecules valproic acid, CHIR99021, DMH1, Repsox, forskolin, Y-27632
      and SP600125 (VCHRFYS) were used to induce MRC-5 cells into neuronal cells in
      vitro. Neuronal markers were analyzed by immunofluorescence staining. The gene
      profiles were analyzed by reverse transcription-quantitative polymerase chain
      reaction. MRC-5 is a human lung fibroblast cell line derived from normal lung
      tissue of a 14-week-old male fetus. The results of the current study demonstrated
      that MRC-5 fibroblasts can be directly converted into neuronal cells using a
      cocktail of seven small molecules (VCHRFYS), with a yield of ~90% Tuj1-positive
      cells after 7 days of induction. Following a further maturation period, these
      chemically-induced neurons possessed neuronal morphology and expressed multiple
      neuron-specific genes. In conclusion, a cocktail of small molecules that can
      convert fibroblasts MRC-5 cells into functional neurons without the exogenous
      genetic factors was identified, which has the potential to be useful in
      neurological disease therapy.

PMID- 29328435
TI  - miR-214 reduces cisplatin resistance by targeting netrin-1 in bladder cancer
      cells.
AB  - miR-214 has been reported to be downregulated in several cancer types, such as
      bladder cancer. However, its involvement in apoptosis and chemoresistance has not
      been investigated. The present study aimed to clarify the biological function of
      miR-214 and potential mechanisms in chemoresistance of bladder cancer cells.
      Reverse transcription-quantitative polymerase chain reaction demonstrated that
      miR-214 was downregulated in bladder cancer tissues compared with the level in
      normal tissues. miR-214 was downregulated in bladder cancer cell lines compared
      with the level in the normal cell line SV-HUC-1. miR-214 mimics were transfected
      into T24 and J82 cell lines to restore its expression. The results indicated that
      miR-214 mimic inhibited proliferation and invasion in these cell lines. In
      addition, miR-214 mimic reduced cisplatin resistance in T24 and J82 cells,
      indicated by the inhibition of cell viability and upregulation of cell apoptosis.
      Western blotting demonstrated that miR-214 mimic was able to upregulate cleaved
      caspase-3 and cleaved poly (ADP-ribose) polymerase (PARP), while downregulate
      caspase-3 and PARP expression, and AKT phosphorylation. Using prediction
      software, it was revealed that the netrin-1 oncoprotein is on the target list of
      miR-214. miR-214 also downregulated netrin-1 protein and mRNA expression levels
      in the T24 and J82 cell lines. Luciferase reporter assays demonstrated that
      netrin-1 acted as a direct target of miR-214. A negative correlation between
      netrin-1 and miR-214 expression in bladder cancer tissues was also observed. In
      addition, cisplatin treatment could induce netrin-1 protein expression in bladder
      cancer cells and miR-214 mimic partly blocked this phenomenon. Netrin-1 plasmid
      transfection inhibited cisplatin-induced apoptosis, upregulated AKT
      phosphorylation, and downregulated caspase-3 and PARP cleavage. Netrin-1 was
      restored in cells transfected with miR-214 mimic using plasmid transfection.
      Netrin-1 transfection restored AKT phosphorylation and blocked caspase/PARP
      cleavage in the T24 and J82 cell lines. In conclusion, the present study
      demonstrated that miR-214 is downregulated in bladder cancer tissues and cell
      lines. miR-214 reduces chemoresistance by targeting netrin-1 in bladder cancer
      cell lines.

PMID- 29328437
TI  - Reduced mitochondrial response sensitivity is involved in the anti-apoptotic
      effect of dexmedetomidine pretreatment in cardiomyocytes.
AB  - Dexmedetomidine is a commonly used alpha2-adreno-ceptor agonist, which affects
      various organs, including providing beneficial effects on the heart. However, the
      mechanism underlying the cardiac benefit remains to be fully elucidated. In the
      present study, it was demonstrated that dexmedetomidine pretreatment on primary
      cultured rat cardiomyocytes protected against reactive oxygen species (ROS)
      induced apoptosis. In terms of the potential mechanism, it was demonstrated that
      dexmedetomidine inhibited mitochondrial biogenesis and mitochondrial respiratory
      complexes, but with increased coupling efficiency. However, dexmedetomidine
      upregulated mitochondrial membrane potential (Deltapsim) and resisted against the
      loss of Deltapsim induced by carbonilcyanide p-triflouromethoxyphenylhydrazone.
      Due to the importance of mitochondria affecting ROS, the present study
      investigated the dexmedetomidine-suppressed mitochondrial response to H2O2
      stimulation, which was explained by suppressed ROS levels and the suppression of
      the increased oxygen consumption rate. Results demonstrated for the first time,
      to the best of our knowledge, a novel protective mechanism for dexmedetomidine on
      cardiomyocytes through the attenuated response of mitochondria towards H2O2,
      which had a protective effect against ROS-induced apoptosis.

PMID- 29328436
TI  - Role of exosomes and exosomal microRNAs in hepatocellular carcinoma: Potential in
      diagnosis and antitumour treatments (Review).
AB  - Communication between hepatocellular carcinoma (HCC) cells and their environment
      is essential for the development and progression of HCC. Exosomes, which are
      microvesicles secreted by a number of cell types, are carriers of intercellular
      information and regulate the tumour microenvironment. Studies have demonstrated
      that exosomes are involved in the communication between HCC cells, endothelial
      cells and stem cells, and that they serve important roles in the metastasis and
      invasion, immune evasion and immunotherapy of HCC. In addition, the mechanism of
      HCC-derived exosome-mediated microRNA (miRNA) transfer is important in the
      environmental modulation of HCC growth and progression. As exosomes can be used
      for detecting and monitoring HCC, they can potentially serve as specific
      biomarkers for early-stage tumours and the tumour metastasis of HCC. Moreover,
      mesenchymal stem cell-derived exosomes can be transfected with miRNAs to inhibit
      HCC development. Therefore, as nucleic acid delivery vehicles, exosomes show a
      tremendous potential for effective treatment against HCC. In the present review,
      recent advances in our understanding of the source, composition and function of
      exosomes in HCC, and their potential value in the early diagnosis and treatment
      of HCC, are summarized.

PMID- 29328438
TI  - Cynandione A inhibits lipopolysaccharide-induced cell adhesion via suppression of
      the protein expression of VCAM-1 in human endothelial cells.
AB  - Cynandione A (CA) is one of the most active compounds in the roots of Cynanchum
      wilfordii, the extracts of which have been used extensively in East Asia to treat
      various diseases including anti-ischemic stroke. In the present study, the anti
      adherent activity of CA in lipopolysaccharide (LPS)-stimulated human umbilical
      vascular endothelial cells (HUVECs) was investigated. CA markedly reduced the
      expression of vascular adhesion molecule-1 (VCAM-1) by LPS in HUVECs. The results
      also demonstrated that CA significantly reduced the expression of pro
      inflammatory and chemoattractant cytokines, including interleukin (IL)-1beta, IL
      6, IL-8, monocyte chemoattractant protein-1 and tumor necrosis factor-alpha, in
      LPS-activated human endothelial cells. CA inhibited the phosphorylation of
      mitogen-activated protein kinases, including the extracellular signal-regulated
      kinase 1/2 and p38 kinases. It was found that CA decreased the IKK/IkappaB-alpha
      phosphorylation of inhibitor of nuclear factor (NF)-kappaB kinase/inhibitor of NF
      kappaB-alpha, suppressed translocation of the NF-kappaB p65 subunit into the
      nucleus and inhibited the transcriptional activity of NF-kappaB. CA also
      decreased human monocyte cell adhesion to endothelial cells in LPS-stimulated
      conditions. These results demonstrated that CA inhibited the protein expression
      of VCAM-1 and pro-inflammatory cytokines by suppressing the transcriptional
      activity of NF-kappaB. The results also suggested that CA may be important in the
      development of anti-inflammatory drugs by inhibiting the expression of cell
      adhesion molecules.

PMID- 29328440
TI  - Methanol extract of Guettarda speciosa Linn. inhibits the production of
      inflammatory mediators through the inactivation of Syk and JNK in macrophages.
AB  - Guettarda speciosa Linn. (G. speciosa, Rubiaceae) has been used as a traditional
      medicinal plant in Asia for the treatment of various inflammatory conditions,
      including cough, fever and maternal postpartum infection. However, the mechanisms
      underlying the anti-inflammatory action of G. speciosa extracts have remained
      elusive. In the present study, the anti-inflammatory effects of the methanol
      extract of G. speciosa (MGS) were investigated in murine macrophages by measuring
      the production of inflammatory mediators and the underlying mechanisms of action
      by performing immunoblotting analysis of proteins that are potentially involved.
      MGS reduced nitric oxide (NO) production through regulation of the expression of
      inducible NO synthase (iNOS) in lipopolysaccharide-activated RAW 264.7 cells;
      however, cyclooxygenase-2, the enzyme responsible for prostaglandin E2
      production, was not affected at the mRNA or protein level. MGS reduced
      interleukin-6 (IL-6) production, but had no effect on tumor necrosis factor (TNF)
      alpha production. In addition, MGS suppressed the transcription of IL-6, but not
      that of IL-1beta and TNF-alpha. The effect of MGS on proinflammatory mediators
      resulted from the inhibition of the activation of spleen tyrosine kinase and c
      Jun N-terminal kinase. In conclusion, the present study suggested that MGS may be
      a potential candidate for development as a therapeutic for alleviating
      inflammation.

PMID- 29328439
TI  - Prognostic significance of hypoxia inducible factor-1alpha expression in patients
      with clear cell renal cell carcinoma.
AB  - The prognostic significance of hypoxia inducible factor-1alpha (HIF-1alpha)
      expression in tumors and the levels of preoperative hemoglobin in clear cell
      renal cell carcinoma (ccRCC), with or without concomitant chronic obstructive
      pulmonary disease (COPD), was investigated. A total of 128 patients with ccRCC
      who underwent surgery were analyzed using retrospective methods. Overall survival
      (OS) and progression free survival (PFS) were analyzed with clinicopathological
      variables, including preoperative hemoglobin levels, COPD and the levels of HIF
      1alpha expression, by Kaplan-Meier survival analysis. Levels of HIF-1alpha
      expression were detected by immunohistochemistry and the multivariate analysis
      was performed by proportional hazards regression. High levels of HIF-1alpha
      expression were associated with a higher pathological stage and histological
      grade in patients with ccRCC (P<0.05). The median OS and PFS of patients with
      concomitant COPD were shorter compared with patients without COPD (P<0.05). The
      levels of serum hemoglobin, HIF-1alpha expression and COPD diagnosis were all
      identified as independent prognostic variables for the OS and PFS of patients
      with ccRCC.

PMID- 29328443
TI  - [Retracted] Effects of cyclin E gene silencing on the proliferation of esophageal
      cancer cell lines, EC9706, Eca109 and KYSE30.
AB  - Subsequently to the publication of this article, an interested reader drew to our
      attention the fact that the six panels shown in Fig. 6 shared several areas of
      identity among them. Following an internal investigation, a laboratory
      technician, who was responsible for editing the pictures, admitted that the data
      as presented in the figure had been manipulated after having mislaid some of the
      original data. The corresponding author of the article takes responsibility for
      this oversight, and therefore the paper is to be retracted from publication. All
      of the named authors agree to this retraction. We deeply regret that these errors
      were allowed to remain in the paper, and extend our apologies to the readership
      of the Journal. [the original article was published in Molecular Medicine Reports
      7: 799-804, 2013; DOI: 10.3892/mmr.2013.1280].

PMID- 29328441
TI  - Ubenimex, an APN inhibitor, could serve as an anti-tumor drug in RT112 and 5637
      cells by operating in an Akt-associated manner.
AB  - Bladder cancer, a common urinary tract tumor, has high mortality and recurrence
      rates associated with metastasis. Aminopeptidase N (APN) expression and
      metastasis have been indicated to be associated with one another. Ubenimex may
      function as an APN inhibitor to inhibit the degradation of the extracellular
      matrix during tumorigenesis. Furthermore, APN has been widely used as an adjuvant
      therapy for the treatment of tumors; however, little information is available
      regarding the impact of ubenimex on patients. Autophagy is suggested to be
      important in the transformation and progression of cancer. Additionally,
      apoptosis, which leads to the rapid demolition of cellular organelles and
      structures, has also been suggested as an important factor. Thus, the present
      study investigated the role of ubenimex in inhibiting migration and invasion by
      downregulating APN expression levels to induce autophagic cell death and
      apoptosis in bladder cancer cells. RT112 and 5637 cell lines were treated with
      varying doses of ubenimex. Cell viability was measured by CCK8 colorimetry and
      flow cytometry. Using fluorescence microscopy, autophagic cell death was assessed
      using acridine orange/ethidium bromide staining. Furthermore, apoptotic cell
      death was assessed using flow cytometry and Trypan blue staining was used to
      evaluate the cell death rate. Protein expression was determined by western blot
      analysis. Matrigel invasion assays were exploited to assess the invasion
      capabilities of 5637 cells. Wound-healing migration assays and Matrigel migration
      assays were exploited to assess the migratory abilities of 5637 cells. Treatment
      with ubenimex was accompanied by decreased Akt expression, indicating that
      ubenimex may have similar functions to Akt inhibitors. Results also indicated
      that ubenimex inhibited cell migration and invasion in bladder cancer cells.
      Furthermore, ubenimex also induced autophagic cell death and apoptosis, which
      suggested that mixed programmed cell death occurred in ubenimex-treated bladder
      cancer cells. The results from the present study suggest that ubenimex may be a
      potential adjuvant therapy for the treatment of bladder cancer.

PMID- 29328442
TI  - Identification of differentially expressed genes and regulatory relationships in
      Huntington's disease by bioinformatics analysis.
AB  - Huntington's disease (HD) is an inherited, progressive neurodegenerative disease
      caused by a CAG expansion in the huntingtin (HTT) gene; various dysfunctions of
      biological processes in HD have been proposed. However, at present the exact
      pathogenesis of HD is not fully understood. The present study aimed to explore
      the pathogenesis of HD using a computational bioinformatics analysis of gene
      expression. GSE11358 was downloaded from the Gene Expression Omnibus andthe
      differentially expressed genes (DEGs) in the mutant HTT knock-in cell model
      STHdhQ111/Q111 were predicted. DEGs between the HD and control samples were
      screened using the limma package in R. Functional and pathway enrichment analyses
      were conducted using the database for annotation, visualization and integrated
      discovery software. A protein-protein interaction (PPI) network was established
      by the search tool for the retrieval of interacting genes and visualized by
      Cytoscape. Module analysis of the PPI network was performed utilizing MCODE. A
      total of 471 DEGs were identified, including ribonuclease A family member 4
      (RNASE4). In addition, 41 significantly enriched Kyoto Encyclopedia of Genes and
      Genomes pathways, as well as several significant Gene Ontology terms (including
      cytokine-cytokine receptor interaction and cytosolic DNA-sensing) were
      identified. A total of 18 significant modules were identified from the PPI
      network. Furthermore, a novel transcriptional regulatory relationship was
      identified, namely signal transducer and activator of transcription 3 (STAT3),
      which is regulated by miRNA-124 in HD. In conclusion, deregulation of 18 critical
      genes may contribute to the occurrence of HD. RNASE4, STAT3, and miRNA-124 may
      have a regulatory association with the pathological mechanisms in HD.

PMID- 29328445
TI  - The effects of interleukin 2 and rAd-p53 as a treatment for glioblastoma.
AB  - Interleukin 2 (IL-2) is an anti-cancer cytokine that stimulates T cell
      propagation, triggering innate and adaptive immunity. IL-2 has been used for
      cancer therapy and has achieved curative effects. Recombinant adenovirus p53
      injection (rAd-p53) is a gene therapeutic agent that may improve the prognosis of
      patients with glioblastoma (GBM). In the present study, the effect of combined IL
      2 and rAd-p53 treatment was studied. The ability of IL-2 to stimulate
      immunoregulation and the ability of p53 to induce apoptosis for GBM was
      researched in the GBM tumor model. In addition, the activity of IL-2 was
      analyzed. The antitumor potential of IL-2 and rAd-p53 was studied using xenograph
      mice carrying GBM cells. Tumor-specific CD4+ and CD8+ T cells were also analyzed
      in the GBM-bearing models. The results demonstrated that IL-2 and rAd-p53 not
      only stimulated tumor-specific cytotoxic T-lymphocyte responses and increased
      regulatory CD4+ and cytotoxic CD8+ T cell proliferation, however additionally
      increased expression of apoptosis-associated genes. The treatment with IL-2 and
      rAd-p53 resulted in tumor regression and prolonged the survival of glioma-bearing
      mice. Taken together, a combination of IL-2 and rAd-p53 treatment combines the
      effects of immunotherapy and oncolytic therapy and may be a comprehensive
      therapeutic schedule for clinical application in future cancer therapies.

PMID- 29328444
TI  - SP1 reduces autophagic flux through activating p62 in gastric cancer cells.
AB  - Gastric cancer is the most common type of gastrointestinal cancer, causing
      mortality worldwide. However, the underlying molecular mechanism in gastric
      cancer progression remains unclear. The autophagic flux was determined in gastric
      cancer cells overexpressing or inhibiting Sp1 transcription factor (SP1) using
      western blotting, reverse transcription-polymerase chain reaction and
      immunofluorescence staining. Luciferase and ChIP assays were performed to detect
      the potential underlying mechanism of SP1 in gastric cancer cells. Lastly,
      immunohistochemistry was also performed on SP1 and p62 expression levels in human
      gastric cancer specimens. It was demonstrated that SP1 diminished autophagic flux
      via activating p62 in gastric cancer. Moreover, SP1 deficiency increased the rate
      of autophagy of gastric cancer cells. Notably, it was observed that SP1 enhanced
      the expression levels of p62 by directly binding to the promoter of p62. Analysis
      of gastric cancer specimen staining established that p62 expression levels were
      increased in SP1-positve gastric tissues. The present study provided evidence for
      a novel mechanism regulating autophagy in gastric cancer cells.

PMID- 29328446
TI  - Clinical significance of Iroquois Homeobox Gene - IRX1 in human glioma.
AB  - The present study aimed to investigate the location, expression and clinical
      significance of Iroquois homeobox gene (IRX1) in human glioma. The expression of
      IRX1 gene in glioma cell lines (U87, U373, LN229 and T98G) and normal brain
      tissue was detected via reverse transcription-polymerase chain reaction. The IRX1
      protein in fresh glioma specimens, with the adjacent normal brain tissue, was
      quantified through western blotting. The archived glioma only specimens from the
      present hospital and glioma specimens with adjacent normal brain tissue, from
      Alenabio biotechnology, were subjected to immunohistochemistry and tissue
      microarray analysis, respectively. The Kaplan-Meier method was employed to assess
      the correlation between the IRX1 level and the overall survival time of the
      patients. IRX1 gene was demonstrated to be expressed at varying levels in U373,
      LN229 and T98G cells, however not in U87 cells and normal brain tissue. Western
      blotting revealed increased IRX1 expression in glioma tissue compared with
      adjacent normal brain tissue. Furthermore, a direct correlation was observed
      between the IRX1 expression and the clinical glioma grade, with a significant
      difference in the gene expression between high grade and low grade glioma
      (P<0.05). Notably, IRX1 was identified to be localized to the cytoplasm in the
      adjacent normal brain and World Health Organization grade I glioma, whereas was
      identified to be present in the nucleus in higher grade glioma. In addition to
      being established as a significant prognostic variable, IRX1 expression was
      positively correlated with the overall survival of glioma patients. IRX1 gene may
      therefore exhibit an oncogenic role in glioma condition, and thus may be of
      clinical importance as a future therapeutic target.

PMID- 29328447
TI  - High-mobility group protein B1 silencing promotes susceptibility of
      retinoblastoma cells to chemotherapeutic drugs through downregulating nuclear
      factor-kappaB.
AB  - The aim of the present study was to investigate the effects of high-mobility
      group protein B1 (HMGB1) silencing on the susceptibility of retinoblastoma (RB)
      cells to chemotherapeutic drugs and the underlying molecular mechanisms. Western
      blot analysis revealed that vincristine (VCR), etoposide (ETO) and carboplatin
      (CBP) significantly increased the expression of HMGB1 in Weri-Rb-1 and Y79 cells
      compared with the untreated control (P<0.01). siRNA HMGB1 and siRNA negative
      control (NC) were transfected to Y79 cells by LipofectamineTM 2000 and, following
      VCR treatment, the expression of HMGB1 and nuclear factor-kappaB (NF-kappaB) was
      analyzed. siRNA HMGB1 transfection silenced HMGB1 expression. The cytotoxicity of
      VCR to cells with and without siRNA HMGB1 was investigated by methyl thiazolyl
      tetrazolium (MTT) assay. siRNA HMGB1 markedly reduced the IC50 value of VCR to RB
      cells through downregulating the expression of NF-kappaB, similar to
      pyrrolidinedithiocarbamate (PDTC). Moreover, following siRNA HMGB1, siRNA NC and
      ammonium PDTC treatment, the apoptosis of RB cells with VCR incubation was
      evaluated by Hoechst staining, and the expression of cleaved caspase-3, cleaved
      poly(ADP-ribose) polymerase (PARP), Beclin 1 and p62 were determined with western
      blot analysis. The LC3 puncta were determined with immunofluorescence assay. The
      results demonstrated that VCR treatment significantly downregulated the
      expression of cleaved caspase-3, cleaved PARP and p62, and upregulated the
      expression of Beclin 1 in RB cells (P<0.01). Similar to the NF-kappaB inhibitor
      PDTC, siRNA HMGB1 significantly promoted apoptosis and suppressed autophagy of
      VCR-treated RB cells through reversing the effects of VCR on these signaling
      molecules (P<0.01). Therefore, HMGB1 silencing promoted the susceptibility of RB
      cells to chemotherapeutic drugs through downregulating NF-kappaB.

PMID- 29328450
TI  - MYBL2 protects against H9c2 injury induced by hypoxia via AKT and NF-kappaB
      pathways.
AB  - Cardiovascular diseases have become one of the major public health problems in
      many countries. The downregulation of MYBL2 was found in H9c2 and native
      cardiomyocytes cells after hypoxia treatment. The present study aimed to
      investigate the effects of MYB proto-oncogene like 2 (MYBL2) on H9c2 injury
      induced by hypoxia. Reverse transcription-quantitative polymerase chain reaction
      and western blot were performed on H9c2 cells to determine the mRNA and protein
      levels of MYBL2, respectively. Small interfering RNA (siRNA) was employed to
      downregulate MYBL2 expression in H9c2 cells to investigate changes in cell
      proliferation and apoptosis. Cell proliferation was assessed by a Cell Counting
      kit-8 assay and the percentage of apoptotic cells was determined using an Annexin
      V-fluorescein isothiocyanate/propidium iodide apoptosis detection kit. The
      nuclear factor-kappaB (NF-kappaB) and AKT signaling pathways in H9c2 cells were
      investigated by western blot analysis. The results demonstrated that the
      overexpression of MYBL2 promoted cell proliferation and suppressed apoptosis.
      Furthermore, overexpression of MYBL2 suppressed the expression of phosphorylated
      (p)-AKT, p-NF-kappaB inhibitor alpha, p-p65 and B-cell CLL/lymphoma 3 (Bcl-3).
      The results indicated that MYBL2 may improve cell viability and inhibit H9c2
      apoptosis via the inhibition of AKT and NF-kappaB pathways. Therefore, MYBL2 may
      be a potential therapeutic target for the treatment of myocardial infarction.

PMID- 29328449
TI  - Bioinformatics analysis to screen key genes implicated in the differentiation of
      induced pluripotent stem cells to hepatocytes.
AB  - Due to the lack of potential organs, hepatocellular transplantation has been
      considered for treating end-stage liver disease. Induced pluripotent stem cells
      (iPSCs) are reverted from somatic cells and are able to differentiate into
      hepatocytes. The present study aimed to investigate the mechanisms underlying
      iPSC differentiation to hepatocytes. GSE66076 was downloaded from the Gene
      Expression Omnibus; this database includes data from 3 undifferentiated (T0), 3
      definitive endoderm (T5), and 3 early hepatocyte (T24) samples across hepatic
      directed differentiation of iPSCs. Differentially expressed genes (DEGs) between
      T0 and T5 or T24 samples were identified using the linear models for microarray
      data package in Bioconductor, and enrichment analyses were performed. Using the
      weighted correlation network analysis package in R, clusters were identified for
      the merged DEGs. Cytoscape was used to construct protein-protein interaction
      (PPI) networks for DEGs identified to belong to significant clusters. Using the
      ReactomeFI plugin in Cytoscape, functional interaction (FI) networks were
      constructed for the common genes. A total of 433 and 1,342 DEGs were identified
      in the T5 and T24 samples respectively, compared with the T0 samples. Blue and
      turquoise clusters were identified as significant gene clusters. In the PPI
      network for DEGs in the blue cluster, the key node fibroblast growth factor 2
      (FGF2) could interact with bone morphogenetic protein 2 (BMP2). Cyclin-dependent
      kinase 1 (CDK1) was demonstrated to have the highest degree (degree=71) in the
      PPI network for DEGs in the turquoise cluster. Enrichment analysis for the common
      genes, including hepatocyte nuclear factor 4alpha (HNF4A) and epidermal growth
      factor (EGF), in the FI network indicated that EGF and FGF2 were enriched in the
      Ras and Rap1 signaling pathways. The present results suggest that FGF2, BMP2,
      CDK1, HNF4A and EGF may participate in the differentiation of iPSCs into
      hepatocytes.

PMID- 29328448
TI  - Association between ACE2/ACE balance and pneumocyte apoptosis in a porcine model
      of acute pulmonary thromboembolism with cardiac arrest.
AB  - Acute pulmonary embolism (APE) is frequently reported in patients with cardiac
      arrest (CA) in emergency care. Pneumocyte apoptosis is commonly observed in the
      lungs following an APE. An important pathological mechanism evoking apoptosis
      during a lipopolysaccharide-induced acute lung injury is the angiotensin
      converting enzyme 2 (ACE2)/ACE imbalance. The present study uses a porcine model
      to examine the anti-apoptotic effects of captopril on APE-CA and the return of
      spontaneous circulation (ROSC). Pigs were randomly assigned into four groups:
      Control, APE-CA, ROSC-saline, and ROSC-captopril. Surviving pigs were euthanized
      at 6 h and lungs were isolated for analysis using several biochemical assays.
      Compared with the control group, the ACE2/ACE ratio was lower in the APE-CA and
      ROSC pigs. In addition, APE-CA pigs had higher Bcl-2-associated X protein (Bax)
      and cleaved caspase-3 levels, and lower B-cell lymphoma-2 (Bcl-2) level compared
      to control pigs. Captopril treatment reduced lung apoptosis, as demonstrated by
      lower TUNEL-positive cells, higher Bcl-2, and lower cleaved caspase-3 protein
      levels in the lung. Notably, the ACE2/ACE ratio was positively correlated with
      Bcl-2 protein levels and Bcl-2/Bax ratio. In conclusion, captopril has a
      protective effect against lung apoptosis following ROSC and that maintaining the
      balance of the ACE2/ACE axis is important for inhibiting pulmonary apoptosis
      during APE.

PMID- 29328451
TI  - A systematic review and meta-analysis of bidirectional effect of arsenic on ERK
      signaling pathway.
AB  - Arsenic is a toxic metal, which ultimately leads to cell apoptosis. ERK is
      considered a key transcriptional regulator of arsenic-induced apoptosis. Due to a
      few controversial issues about arsenic-mediated extracellular signal-regulated
      MAP kinases (ERK) signaling, a meta-analysis was performed. Subgroup analyses
      demonstrated that high doses (>=2 umol/l) of arsenic increased the expression of
      Ras, ERK, ERK1, ERK2, phosphorylated (p)-ERK, p-ERK1, and p-ERK2, while low doses
      (<2 umol/l) decreased the expression of Ras, ERK1, p-ERK, and p-ERK2 when
      compared to control groups. Long term exposure (>24 h) to arsenic led to
      inhibition of expression of ERK1, p-ERK1, and p-ERK2, whereas short-term exposure
      (<=24 h) triggered the expression of ERK1, ERK2, p-ERK, p-ERK1, and p-ERK2.
      Furthermore, normal cells exposed to arsenic exhibited higher production levels
      of Ras and p-ERK. Conversely, exposure of cancer cells to arsenic showed a lower
      level of production of Ras and p-ERK as well as higher level of p-ERK1 and p-ERK2
      as compared to control group. Short-term exposure of normal cells to high doses
      of arsenic may promote ERK signaling pathway. In contrast, long-term exposure of
      cancer cells to low doses of arsenic may inhibit ERK signaling pathway. This
      study may be helpful in providing a theoretical basis for the diverging result of
      arsenic adverse effects on one hand and therapeutic mechanisms on the other
      concerning arsenic-induced apoptosis.

PMID- 29328452
TI  - HIF-1alpha-induced upregulation of lncRNA UCA1 promotes cell growth in
      osteosarcoma by inactivating the PTEN/AKT signaling pathway.
AB  - Increasing evidence indicates that long non-coding RNAs (lncRNAs) play an
      important role in multiple biological processes including cell growth,
      differentiation, proliferation and invasion. Urothelial carcinoma associated 1
      (UCA1) is a highly conserved nuclear ncRNA and a key regulator of cell
      proliferation and apoptosis in several types of cancers. However, its role in
      osteosarcoma progression is not well known. In the present study, we aimed to
      determine the biological role of UCA1 in osteosarcoma progression. RT-qPCR
      analysis showed that UCA1 expression was significantly increased in osteosarcoma
      cell lines and promoted cell growth in osteosarcoma. We then sought to determine
      the mechanism underlying the upregulation of UCA1 in osteosarcoma. Luciferase
      reporter assay and chromatin immunoprecipitation assay suggested that lncRNA UCA1
      was induced by HIF-1alpha and HIF-1alpha interacts with the HIF-1alpha response
      element in the promoter region of UCA1. In addition, the gain- and loss-of
      functional assay showed that HIF-1alpha promoted osteosarcoma cell growth through
      inducing the UCA1 expression level. More importantly, Cignal Signal Transduction
      Reporter Array and western blot assay showed that lncRNA UCA1 inactivated the
      PTEN/AKT signaling pathway. Finally, we observed that HIF-1alpha induced cell
      growth through the UCA1/PTEN/AKT signaling pathway. To conclude, our integrated
      approach demonstrates that UCA1 confers a tumor promoter function by promoting
      cell proliferation and silencing of the PTEN/AKT signaling pathway in
      osteosarcoma. Thus, UCA1 can serve as a promising therapeutic target for
      osteosarcoma patients.

PMID- 29328453
TI  - Aldosterone is involved in the pathogenesis of obesity-related glomerulopathy
      through activation of Wnt/beta-catenin signaling in podocytes.
AB  - Obesity-related glomerulopathy (ORG) is morphologically characterized by
      glomerulomegaly with or without observable focal segmental glomerulosclerosis
      under light microscope, with decreased podocyte density and number, and with
      increased foot-process width observed under electron microscope. The severity of
      podocyte injury is correlated with the degree of proteinuria and renal
      dysfunction. However, the pathogenesis of ORG is not well understood. The aim of
      the present study was to explore the possible pathogenic role of aldosterone
      (ALDO) in ORG. In the in vivo animal experiments, body weight, Lee's obesity
      index, abdominal fat index, urinary protein excretion, average glomerular
      diameter were significantly increased, the mRNA and protein expression of
      podocyte-associated molecules including nephrin, podocin, podoplanin and
      podocalyxin were significantly reduced, and the Wnt/beta-catenin signaling
      pathway was activated in ORG model mice compared with the Control mice, whereas
      the administration of spironolactone significantly ameliorated these effects. In
      the in vitro experiments on cultured podocytes, the mRNA and protein expression
      levels of the aforementioned podocyte-associated molecules were significantly
      downregulated and the Wnt/beta-catenin signaling pathway was activated following
      ALDO stimulation, whereas eplerenone significantly attenuated all the above
      effects. Dickkopf-related protein 1 (DKK1), an inhibitor of Wnt/beta-catenin
      signaling pathway, also reduced the effects of ALDO exposure on the expression of
      podocyte-associated molecules. The present study hypothesized that ALDO may be
      involved in the pathogenesis of ORG through the activation of Wnt/beta-catenin
      signaling pathway in podocytes.

PMID- 29328454
TI  - Resveratrol ameliorates depressive disorder through the NETRIN1-mediated
      extracellular signal-regulated kinase/cAMP signal transduction pathway.
AB  - Depressive disorder is a mental health disorder caused by the dysfunction of
      nerve regeneration, neuroendocrine and neurobiochemistry, which frequently
      results in cognitive impairments and disorder. Evidence has shown that
      resveratrol offers benefits for the treatment of depressive disorder. In the
      present study, the therapeutic effects of resveratrol were investigated and the
      potential mechanisms mediated by resveratrol were analyzed in hippocampal neuron
      cells. The anti-oxidative stress and anti-inflammatory properties of resveratrol
      were also examined in vitro and in vivo. The results revealed that resveratrol
      administration inhibited the inflammation in hippocampal neuron cells induced by
      ouabain. Oxidative stress in the hippocampal neuron cells was ameliorated by
      resveratrol treatment in vitro and in vivo. In addition, the apoptosis of
      hippocampal neuron cells was inhibited by the upregulation of anti-apoptotic
      genes, including P53, B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated death
      promoter, and the downregulation of the cleaved caspase-3 and caspase-9. The
      analysis of the mechanism revealed that that resveratrol treatment suppressed the
      apoptosis of hippocampal neuron cells through the NETRIN1-mediated extracellular
      signal-regulated kinase/cAMP signal transduction pathway. The results of the in
      vivo assay showed that resveratrol treatment led to improvements in cognitive
      competence, learning memory ability and anxiety in a mouse model of depressive
      disorder induced by ouabain. In conclusion, these results indicated that
      resveratrol treatment had protective effects against oxidative stress and
      neuroinflammatory pathogenesis through the NETRIN1-mediated extracellular signal
      regulated kinase/cAMP signal transduction pathway, suggesting that resveratrol
      treatment may be a potential antidepressant agent for the treatment of depressive
      disorder.

PMID- 29328456
TI  - p21 protects cardiomyocytes against ischemia-reperfusion injury by inhibiting
      oxidative stress.
AB  - Ischemic heart disease is a major health threat, resulting in a large number of
      mortalities annually worldwide. Oxidative stress is one of the main causes of
      cell death during ischemia-reperfusion (IR) injury. Cyclin dependent kinase
      inhibitor 1A (known as p21) is important in protecting tissues against IR injury,
      however the mechanism remains unknown. In the present study, oxygen-glucose
      deprivation and subsequent reoxygenation (OGD/R) in H9c2 heart-derived myocytes
      was used as a model to study myocardial IR injury in vitro. mRNA and protein
      expression levels were determined by reverse transcription-quantitative
      polymerase chain reaction and western blotting, respectively. The levels of
      reactive oxygen species were measured using the fluorescence dye 2',7'
      dichlorodihydrofluorescein diacetate. The present data demonstrated that p21
      expression was upregulated by tumor protein p53 (p53) in H9c2 cells exposed to
      OGD/R. p21 protected H9c2 cells against OGD/R-induced oxidative stress. In
      addition, p21 mediated upregulation of NF-E2-related factor-2 (Nrf2), a regulator
      of antioxidant responses, which in turn suppressed cell death in H9c2 cells
      subjected to OGD/R. Thus, activation of the p53/p21/Nrf2 signaling pathway may be
      an important adaptive response that limits oxidative injury during IR.

PMID- 29328455
TI  - Role of miR-21 in the growth and metastasis of human salivary adenoid cystic
      carcinoma.
AB  - Aberrant microRNA (miRNA/miR) expression has been reported in various cancer
      types. miR-21, which is considered to be a proto-oncogene and is frequently
      overexpressed in certain cancer types, has been implicated in tumorigenesis. The
      aim of the present study was to investigate the effect of miR-21 degradation on
      tumor progression and its potential mechanisms in human salivary adenoid cystic
      carcinoma (SACC) development. Results of reverse transcription-quantitative
      polymerase chain reaction analysis indicated that SACC cells with high metastatic
      potential (SACC-LM cells) exhibited a significantly higher expression of miR-21
      compared with SACC cells with a lower metastatic potential (SACC-83 cells). In
      addition, following transfection of SACC-LM cells with miR-21 inhibitor, cell
      viability was reduced, which may be a result of reduced cell proliferation and
      metastasis, and the induction of apoptosis, as determined by Cell Counting Kit-8,
      wound healing, Matrigel invasion and flow cytometry assays. Furthermore,
      bioinformatics analysis indicated that programmed cell death 4 (PDCD4),
      phosphatase and tensin homolog deleted on chromosome ten (PTEN) and B-cell
      lymphoma (Bcl)-2 are potential target genes of miR-21. Therefore, western
      blotting was performed to investigate the expression of these proteins, and the
      results demonstrated that miR-21 expression level was negatively associated with
      PDCD4 and PTEN protein expression, and positively associated with Bcl-2 protein
      expression, in SACC-LM cells, indicating that miR-21 may promote SACC progression
      via PDCD4, PTEN and Bcl-2. In conclusion, the present study indicates that miR-21
      may be a novel target for SACC therapy and provide a novel basis for the clinical
      treatment of SACC.

PMID- 29328457
TI  - MicroRNA-34a inhibits liver cancer cell growth by reprogramming glucose
      metabolism.
AB  - MicroRNAs (miRs) have been proposed as minimally invasive prognostic markers for
      various types of cancer, including liver cancer, which is one of the most common
      cancers worldwide. In the present study, the expression of miR-34a in human liver
      cancer tissues and cell lines was evaluated and the effects of miR-34a on cell
      proliferation, invasion and glycolysis in hepatocellular carcinoma (HCC) cells
      were determined. The results indicated that miR-34a was downregulated in human
      liver cancer tissues. Overexpression of miR-34a significantly inhibited liver
      cancer cell proliferation and clone formation. In terms of the underlying
      mechanism, miR-34a was indicated to negatively regulate the expression of lactate
      dehydrogenase A (LDHA), which consequently inhibited LDHA-dependent glucose
      uptake in the cancer cells, as well as cell proliferation and invasion.
      Collectively, these data suggest that miR-34a functions as a negative regulator
      of glucose metabolism and may serve as a novel marker for liver cancer prognosis.

PMID- 29328459
TI  - alpha-solanine enhances the chemosensitivity of esophageal cancer cells by
      inducing microRNA-138 expression.
AB  - Esophageal cancer is a common malignant tumor worldwide. Inherent and acquired
      drug resistance are the major challenges faced in anticancer chemotherapy. This
      study aimed to explore the effects of alpha-solanine in regards to the
      chemosensitivity of esophageal cancer cells. We found that alpha-solanine
      enhanced the sensitivity of EC9706 and KYSE30 cells to 5-flurouracil (5-FU) and
      cisplatin (Cis) by promoting drug-induced apoptosis. qRT-PCR and western blotting
      results showed that alpha-solanine treatment promoted miR-138 expression and
      decreased survivin expression in EC9706 and KYSE30 cells. alpha-solanine also
      enhanced the inhibitory effects of 5-Fu and Cis in EC9706 transplanted tumors in
      mouse models. Dual-Luciferase reporter assay results confirmed survivin as the
      direct target gene of miR-138. MiR-138 inhibited survivin expression in EC9706
      and KYSE30 cells. And miR-138 mimic and si-survivin had similar effects with
      alpha-solanine in suppressing survivin expression and promoting cancer cell
      death. miR-138 inhibitor reversed the chemosensitivity-enhancing effect of alpha
      solanine. In EC9706 and KYSE30 cells, survivin overexpression rescued the cancer
      cells from apoptosis caused by alpha-solanine and miR-138 mimic expression. From
      these findings, we conclude that alpha-solanine enhanced the chemosensitivity of
      esophageal cancer cells to chemotherapy via the miR-138/survivin pathway. This
      study provides insight into the molecular mechanism underlying the
      chemosensitivity-enhancing function of alpha-solanine and suggests a new
      chemotherapeutic strategy for esophageal cancer treatment.

PMID- 29328460
TI  - Terrein inhibits migration of human breast cancer cells via inhibition of the Rho
      and Rac signaling pathways.
AB  - Breast cancer is the most common cancer in women worldwide. Progression and
      aggressiveness of breast cancer is usually associated with its migration and
      invasion abilities. Recently, natural products with potential anticancer activity
      have become attractive candidates for alternative treatment of cancer. A fungal
      metabolite, terrein, isolated from the Aspergillus terreus has been revealed to
      exhibit selective anticancer activity; although this molecule has a variety of
      biological activities. The inhibitory effect on cell proliferation in hepatoma,
      keratinocytes, and lung cancer cells was due to cell cycle arrest without
      induction of apoptosis. In contrast, its effects on cervical and breast cancer
      cells were mediated through activation of the apoptotic process. However, the
      effect of terrein on cell migration and invasion has not been explored. In the
      present study we analyzed the molecular effects of terrein on cell adhesion, cell
      migration, and cell invasion using two breast cancer cell lines, MCF-7 and MDA-MB
      231, which exhibit different levels of invasiveness. Terrein induced apoptosis in
      both breast cancer cell lines in a dose-dependent manner. In addition, at a non
      toxic concentration terrein exhibited a weak inhibition of cell adhesion, using
      either fibronectin or type IV collagen as substrates. Notably, terrein
      significantly inhibited both the migration and invasion abilities of MDA-MB-231
      cells at the same non-toxic concentration. A marked decrease in MMP-2 and MMP-9
      transcripts, as evaluated by real-time PCR, confirmed the anti-invasion effect of
      terrein at the transcriptional level. Western blot analyses revealed that terrein
      treatment suppressed RhoB expression and reduced Rac1 phosphorylation, leading to
      Rho GTPase inhibition. In addition, terrein-treated MCF-7 and MDA-MB-231 cells
      both displayed a scattered pattern of migration, suggesting that the suppression
      of RhoB and Rac1 disturbed the collective migration processes of breast cancer
      cells.

PMID- 29328458
TI  - Chitosan conduit combined with hyaluronic acid prevent sciatic nerve scar in a
      rat model of peripheral nerve crush injury.
AB  - In the present study, the effects of hyaluronic acid (HA) combined with chitosan
      conduit on peripheral nerve scarring and regeneration were investigated in a rat
      model of peripheral nerve crush injury. A total of 60 Sprague-Dawley rats were
      randomly distributed into four groups (15 rats in each group), in which the nerve
      was either not treated (control group) or treated with chitosan conduit,
      hyaluronic acid, or chitosan conduit coupled with hyaluronic acid following clamp
      injury to the sciatic nerve. The surgical sites were evaluated by assessing the
      sciatic functional index, the degree of scar adhesions, the numbers of myelinated
      nerve fibers, the average diameter of myelinated nerve fibers and the myelin
      sheath thickness. Larger epineurial scar thickness was observed in the control
      groups compared with the treatment groups at 4, 8 and 12 weeks following surgery.
      There was no significant difference in scar adhesion among the four groups at 4
      weeks following surgery. However, animals receiving chitosan coupled with HA
      demonstrated better neural recovery, as measured by reduced nerve adherence to
      surrounding tissues, less scar adhesion, increased number of axons, nerve fiber
      diameter and myelin thickness. In conclusion, the application of chitosan conduit
      combined with HA, to a certain extent, inhibited sciatic nerve extraneural
      scaring and adhesion, and promoted neural regeneration and recovery.

PMID- 29328461
TI  - Anti-inflammatory effects of gambogic acid in murine collagen-induced arthritis
      through PI3K/Akt signaling pathway.
AB  - Garcinia angustifolia is a dry resin secreted by Garcinia cambogia, which has the
      functions of breaking blood, detoxifying, stopping bleeding and killing insects.
      It is used for the treatment of cancer and brain edema. Gambogic acid is the
      primary active ingredient. The present study aimed to investigate the anti
      inflammatory and antiproliferative effects of gambogic acid on arthritis and the
      possible mechanisms. It was demonstrated that gambogic acid decreased arthritic
      scores in murine collagen-induced arthritic mice. The tumor necrosis factor (TNF)
      alpha, interleukin (IL)-1beta, IL-6 and IL-18 concentrations, and caspase-3 and
      caspase-9 were significantly inhibited by gambogic acid in arthritic mice.
      Gambogic acid decreased matrix metalloproteinases (MMP)-2, MMP-9, nuclear factor
      (NF)-kappaB and phosphorylated-p38 protein expression, and increased tissue
      inhibitors of matrix metalloproteases-1 (TIMP-1) protein expression in arthritic
      mice. Furthermore, the phosphoinositide 3-kinase (PI3K)/AKT serine/threonine
      kinase (Akt) signaling pathway was induced in arthritic mice treated with
      gambogic acid. The results suggested that gambogic acid induced anti-inflammatory
      effects in murine collagen-induced arthritis, through the PI3K/Akt signaling
      pathway, and offers future potential for application in arthritis patients.

PMID- 29328462
TI  - Serum and glucocorticoid-regulated kinase 1 (SGK1) is a predictor of poor
      prognosis in non-small cell lung cancer, and its dynamic pattern following
      treatment with SGK1 inhibitor and gamma-ray irradiation was elucidated.
AB  - The tumor suppressor gene p53 and its dynamic patterns have caused widespread
      attention in the field of cancer research. Serum and glucocorticoid-regulated
      kinase 1 (SGK1) with features of serine/threonine kinase activity, which also
      contributes to the structural and functional similarities with the AKT family of
      kinases, is a key enzyme in the regulation of immune responses in tumor cells,
      and SGK1 was noted to be expressed in close relation to p53 protein levels, and
      there exists a negative feedback pathway between intracellular SGK1 and p53.
      Noteworthy, SGK1 was detected to play a role in the development of resistance to
      cancer chemotherapy. In this study, we demonstrated that high SGK1 expression had
      strong prognostic value for reduced overall survival in NSCLC patients. Detection
      of SGK1 collectively was helpful to predict the prognosis of NSCLC. We also
      identified the expression level of SGK1 and the p53 pathway including downstream
      apoptotic proteins under the stimulation of gamma-radiation and SGK1 inhibitor
      GSK650394, which presented a series of dynamic fluctuations. Our results suggest
      that SGK1 dynamics could play an important role in cell signaling, which is
      capable of directly influencing NSCLC cellular fate decisions.

PMID- 29328463
TI  - Construction and investigation of lncRNA-associated ceRNA regulatory network in
      papillary thyroid cancer.
AB  - Increasing evidence has experimentally proved the competitive endogenous RNA
      (ceRNA) hypothesis that long non-coding RNA (lncRNA) can affect the expression of
      RNA targets by competitively combining microRNA (miRNA) via miRNA response
      elements. However, an extensive ceRNA network of thyroid carcinoma in a large
      cohort has not been evaluated. We analyzed the RNAseq and miRNAseq data of 348
      cases of primary papillary thyroid cancer (PTC) patients with clinical
      information downloaded from The Cancer Genome Atlas (TCGA) project to search for
      potential biomarkers or therapeutic targets. A computational approach was applied
      to build an lncRNA-miRNA-mRNA regulatory network of PTC. In total, 780 lncRNAs
      were detected as collectively dysregulated lncRNAs in all 3 PTC variants compared
      with normal tissues (fold change >2 and false discovery rate <0.05). The
      interactions among 45 lncRNAs, 13 miRNAs and 86 mRNAs constituted a ceRNA network
      of PTC. Nine out of the 45 aberrantly expressed lncRNAs were related to the
      clinical features of PTC patients. However, the expression levels of 3 lncRNAs
      (LINC00284, RBMS3-AS1 and ZFX-AS1) were identified to be tightly correlated with
      the patients overall survival (log-rank, P<0.05). The present study identified a
      list of specific lncRNAs associated with PTC progression and prognosis. This
      complex ceRNA interaction network in PTC may provide guidance for better
      understanding the molecular mechanisms underlying PTC.

PMID- 29328464
TI  - Inhibition of Gli leads to antitumor growth and enhancement of cisplatin-induced
      cytotoxicity in large cell neuroendocrine carcinoma of the lung.
AB  - Large cell neuroendocrine carcinoma (LCNEC) of the lung is a highly aggressive
      tumor without established standard treatment. The Hedgehog (Hh) signal, which is
      critical in embryogenesis, is known to play important roles in maintaining a
      malignant phenotype in various cancers. The present study explored the
      possibility of targeting the Hh signal in the treatment of LCNEC by suppressing
      Hh downstream molecules, Smoothened (Smo) and GLI family zinc finger 1/2
      (Gli1/2), in 3 human LCNEC cell lines. Smo inhibitor, BMS-833923, and Gli
      inhibitor, GANT61, downregulated Gli1 and 2, resulting in the suppression of the
      cell viability of the 3 cell lines as assessed using an MTT assay. The
      downregulation of Gli1 and/or Gli2 using siRNA for each gene also led to cell
      growth inhibition in the 3 cell lines. The downregulation of Gli1/2 made the
      cells more sensitive to cisplatin, resulting in increased apoptosis. These
      findings suggest that the Hh signaling pathway may be a candidate target for the
      treatment of LCNEC of the lung.

PMID- 29328465
TI  - Effects of diphyllin as a novel V-ATPase inhibitor on TE-1 and ECA-109 cells.
AB  - Diphyllin is a natural component of traditional Chinese medicine, which
      effectively inhibits V-ATPase activity and affects the progression of cancer.
      However, few studies have been conducted on esophageal cancer, and the mechanisms
      remain to be elucidated. The present study revealedthat diphyllin inhibited
      proliferation and induced S arrest in esophageal cancer cell lines TE-1 and ECA
      109. Further experiments revealed that diphyllin inhibited V-ATPase activity and
      decreased the mRNA expression of mammalian target of rapamycin complex 1
      (mTORC1), hypoxia-inducible factor-1alpha (HIF-1alpha), and vascular endothelial
      growth factor (VEGF). The present study also revealed that diphyllin inhibited
      proliferation and reduced the formation of new blood vessels. Diphyllin inhibited
      blood metastasis by regulating the mTORC1/HIF-1alpha-/VEGF pathway, therefore it
      could be considered as a new V-ATPase inhibitor to treat esophageal cancer.

PMID- 29328466
TI  - Knockdown of immature colon carcinoma transcript 1 induces suppression of
      proliferation, S-phase arrest and apoptosis in leukemia cells.
AB  - Immature colon carcinoma transcript 1 (ICT1), a human mitochondrial translation
      release factor, is a ribosome-dependent codon-independent peptidyl-tRNA
      hydrolase. ICT1-deficiency has been recognized as a cell growth inhibitor of
      hepatoblastoma and glioblastoma multiforme. To explore the role of ICT1 in human
      leukemia, 2 short hairpin RNAs (shRNAs) targeting ICT1 sequences were designed in
      leukemia U937 cells. The successful infection of ICT1 in the U937 cells was
      observed under a fluorescence microscope and further quantified by western
      blotting and quantitative real-time PCR (qRT-PCR) analysis. Tetrazolium dye (MTT)
      assay revealed a significant decrease in proliferation of ICT1-knockdown U937
      cells on the fourth and fifth day as compared with the control. Depletion of ICT1
      resulted in an increase in S phase and sub-G1 (representing cell apoptosis)
      fractions. Annexin V-APC/7-AAD staining assay confirmed that knockdown of ICT1
      played a crucial role in boosting early and late apoptotic programs in U937
      cells. Downregulation of ICT1 also altered cyclin A2 transcription expression,
      caspase-3 activity and p21 protein expression. Additionally, decreased levels of
      heat shock protein 27 (HSP27) phosphorylation at Ser78 was correlated with
      knockdown of ICT1 in U937 cells. Thus, we concluded that the regulatory role of
      ICT1 in leukemia may be used as a potential therapeutic target for the treatment
      of leukemia.

PMID- 29328467
TI  - Aspirin and metformin exhibit antitumor activity in murine breast cancer.
AB  - Studies have shown that aspirin and metformin play important roles in
      chemoprevention and repression of breast cancers, even though the exact mechanism
      remains unclear. Aspirin is capable of stimulating apoptosis through
      prostaglandin-dependent or prostaglandin-independent pathways. Metformin inhibits
      cell growth by enhancing the tumor suppressive function of transforming growth
      factor (TGF-beta). In the present study, we report a new link between aspirin,
      metformin, TGF-beta1 and murine breast cancer inhibition. Specifically, we showed
      that aspirin and metformin enhanced 4T1 cell apoptosis by inducing secretion of
      TGF-beta1, whereas estradiol weakened the effect.

PMID- 29328468
TI  - MicroRNA-136 inhibits prostate cancer cell proliferation and invasion by directly
      targeting mitogen-activated protein kinase kinase 4.
AB  - Prostate cancer (PCa) is the second most common type of cancer and the 6th
      leading cause of cancer-associated mortality worldwide. Accumulated evidence
      suggests that PCa initiation and progression are controlled by microRNAs
      (miRNAs). Therefore, investigating PCa-associated miRNAs may provide novel
      biomarkers for the diagnosis and treatment of patients with PCa. In the present
      study it was demonstrated that miRNA-136 (miR-136) expression was significantly
      downregulated in PCa tissues and cell lines. The resumption of miR-136 expression
      suppressed cell proliferation and invasion in PCa cells. Bioinformatics analysis
      predicted that mitogen-activated protein kinase kinase 4 (MAP2K4) was a direct
      target of miR-136. This prediction was experimentally confirmed by a luciferase
      reporter assay, RT-qPCR and western blot analysis. MAP2K4 was highly expressed in
      PCa tissues and inversely correlated with the miR-136 expression level.
      Additionally, the restoration of MAP2K4 expression significantly blocked the
      inhibitory effects of miR-136 on cell proliferation and invasion in PCa cells.
      Therefore, miR-136 may suppress the proliferation and invasion of PCa cells by
      targeting MAP2K4 and may be a novel candidate target for cancer therapy against
      PCa.

PMID- 29328469
TI  - Human cytomegalovirus UL141 protein interacts with CELF5 and affects viral DNA
      replication.
AB  - Human cytomegalovirus (HCMV) infection is the primary viral cause of congenital
      abnormalities and mental retardation in newborns. The HCMV UL141-encoded
      glycoprotein has been previously revealed to inhibit the cell-surface expression
      of cluster of differentiation (CD)155, CD122, tumor necrosis factor-related
      apoptosis-inducing ligand death (TRAIL)-receptor 1 (R1) and TRAIL-receptor 2
      (R2), thus protecting virally-infected cells by allowing them to escape natural
      killer cell-mediated cytotoxicity. The present study investigated the interaction
      between HCMV UL141 and human fetal brain cDNA to elucidate the possible effects
      of UL141 on the nervous system. The findings of the current study demonstrate
      that the HCMV UL141 protein directly interacts with the human protein CUGBP Elav
      like family member 5 (CELF5) via yeast two-hybrid screening, this interaction was
      confirmed by glutathione S-transferase pull-down and co-immunoprecipitation
      assays. Additionally, the present study demonstrated that the UL141 protein co
      localizes with CELF5 in the cytoplasm of 293 cells using fluorescence confocal
      microscopy. CELF5 overexpression in a stably-expressing cell line significantly
      increased viral DNA copy number and titer in HCMV-infected U373MG cells. However,
      reducing CELF5 expression via specific small interfering RNAs did not affect
      viral DNA copy number or titer in HCMV-infected cells. The current findings
      suggest that the interaction between UL141 and CELF5 may be involved in
      modulating viral DNA synthesis and progeny production. Therefore, CELF5 may
      represent a possible mechanism for regulation of HCMV genomic DNA synthesis,
      which is a key step during HCMV infection leading to neurological disease.

PMID- 29328470
TI  - Cobalt-protoporphyrin enhances heme oxygenase 1 expression and attenuates liver
      ischemia/reperfusion injury by inhibiting apoptosis.
AB  - The aim of the present study was to investigate the preconditioning effect and
      underlying mechanisms of cobalt-protoporphyrin (CoPP) in a mouse model of liver
      ischemia-reperfusion (I/R) injury. Mice were divided into five groups: Sham
      operated (control), I/R, I/R + CoPP, I/R + CoPP and zinc-protoporphyrin (ZnPP)
      and I/R + ZnPP. Serum levels of aspartate transaminase (AST) and alanine
      aminotransferase (ALT) were detected using commercial kits. The expression of the
      pro-apoptotic protein caspase-3 was detected by immunohistochemistry and the
      expression levels of the anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) and
      heme oxygenase 1 (HO-1) were analyzed by western blotting. Sections of liver
      tissue were stained with hematoxylin and eosin to observe pathologic alterations.
      Furthermore, hepatocyte apoptosis was detected using a terminal deoxynucleotidyl
      transferase dUTP nick end labeling (TUNEL) assay. AST and ALT levels of the CoPP
      preconditioned group were significantly reduced compared with the IR injury group
      (P<0.05) and liver damage was attenuated. The expression levels of the pro
      apoptotic protein caspase3 was inhibited and those of HO-1 and Bcl-2 were
      increased in the CoPP group compared with the I/R group; the opposite results
      were observed in the ZnPP group. Furthermore, the percentage of apoptotic cells
      as detected by TUNEL was significantly decreased in the CoPP group compared with
      the I/R group (P<0.05); these protective effects were abrogated by ZnPP. In
      conclusion, the results of the present study suggested that CoPP may induce HO-1
      overexpression and produce anti-apoptotic effects in liver I/R injury.

PMID- 29328471
TI  - Prostaglandin E2 receptor EP4 is involved in the cell growth and invasion of
      prostate cancer via the cAMP-PKA/PI3K-Akt signaling pathway.
AB  - Prostate cancer (PCa) is one of the most prevalent diagnosed malignancies
      globally. Previous studies have demonstrated that prostaglandin E2 (PGE2) is
      closely associated with the tumorigenesis and progression of PCa. However, the
      underlying molecular mechanisms remain unclear and require further investigation.
      Matrix metalloproteinases (MMPs), receptor activator of nuclear factor-kappaB
      ligand (RANKL) and runt-related transcription factor 2 (RUNX2), which are
      involved in cell growth and bone metastasis, are frequently activated or
      overexpressed in various types of cancer, including PCa. The present study was
      designed to investigate the associations between PGE2 and the PGE2 receptor EP4,
      and MMPs, RANKL and RUNX2 in PCa, and to define their roles in PCa cell
      proliferation and invasion in addition to understanding the molecular mechanisms.
      The results of western blotting and reverse transcription-quantitative polymerase
      chain reaction demonstrated that the protein and the mRNA expression levels of
      MMP-2, MMP-9, RANKL and RUNX2 in PC-3 cells were significantly upregulated by
      treatment with PGE2, respectively, and knockdown of these proteins blocked PGE2
      induced cell proliferation and invasion in PC-3 cells, as determined by Cell
      Counting Kit-8 and Matrigel invasion assays, respectively. The effect of PGE2 on
      the protein and mRNA expression levels was primarily regulated via the EP4
      receptor. EP4 receptor signaling activates the cyclic (c)AMP-protein kinase A
      (PKA) signaling pathway, and forskolin, an activator of adenylate cyclase (AC),
      exhibited similar effects to an EP4 receptor agonist on the protein expression,
      while SQ22536, an inhibitor of AC, inhibited the protein expression. These
      results confirmed that the AC/cAMP pathway may be involved in EP4 receptor
      mediated upregulation of protein expression. By using a specific inhibitor of
      PKA, it was also demonstrated that cAMP/PKA was also involved in the EP4 receptor
      mediated upregulation of protein expression. In addition to the signaling pathway
      involving PKA, the EP4 receptor also exerts activities through activation of Akt
      kinase. The results in the present study confirmed the hypothesis that EP4
      receptor-mediated protein expression in PCa cells that were pretreated with a
      specific inhibitor of phosphatidylinositol 3-kinase (PI3K) was significantly
      inhibited. In conclusion, the results of the present study indicate that PGE2
      significantly upregulated the mRNA and protein expression levels of the MMP-2,
      MMP-9, RANKL and RUNX2, and the EP4 receptor was involved in the cell
      proliferation and invasion of PCa via the cAMP-PKA/PI3K-Akt signaling pathway.
      These results may provide novel insight into potential therapeutic strategies for
      the prevention and treatment of PCa.

PMID- 29328473
TI  - Detection of high-grade neoplasia in air-dried cervical PAP smears by a microRNA
      based classifier.
AB  - Recent studies have shown that changes in the expression levels of certain
      microRNAs correlate with the degree of severity of cervical lesions. The aim of
      the present study was to develop a microRNA-based classifier for the detection of
      high-grade cervical intraepithelial neoplasia (CIN >=2) in cytological samples
      from patients with different high-risk human papillomavirus (HR-HPV) viral loads.
      For this purpose, raw RT-qPCR data for 25 candidate microRNAs, U6 snRNA and human
      DNA in air-dried PAP smears from 174 women with different cervical cytological
      diagnoses, 144 of which were HR-HPV-positive [40 negative for intraepithelial
      lesion or malignancy (NILM), 34 low-grade squamous intraepithelial lesions (L
      SIL), 57 high-grade squamous intraepithelial lesions (H-SIL), 43 invasive
      cancers], were statistically processed. The expression level changes of various
      individual microRNAs were found to be significantly correlated with the
      cytological diagnosis but the statistical significance of this correlation was
      critically dependent on the normalization strategy. We developed a linear
      classifier based on the paired ratios of 8 microRNA concentrations and cellular
      DNA content. The classifier determines the dimensionless coefficient (DF value),
      which increases with the severity of cervical lesion. The high- and low-grade
      CINs were better distinguished by the microRNA classifier than by the measurement
      of individual microRNA levels with the use of traditional normalization methods.
      The diagnostic sensitivity of detecting high-grade lesions (CIN >=2) with the
      developed microRNA classifier was 83.4%, diagnostic specificity 81.2%, ROC
      AUC=0.913. The analysis can be performed with the same nucleic acid preparation
      as used for HPV testing. No statistically significant correlation of the DF value
      and HR-HPV DNA load was found. The DF value and the HR HPV presence and viral DNA
      load may be regarded as independent criteria that can complement each other in
      molecular screening for high-grade cervical intraepithelial neoplasia. Although
      it has several limitations, the present study showed that the small-scale
      analysis of microRNA signatures performed by simple PCR-based methods may be
      useful for improving the diagnostic/prognostic value of cervical screening.

PMID- 29328472
TI  - Combined analysis of gene expression and genome binding profiles identified
      potential therapeutic targets of ciclopirox in Ewing sarcoma.
AB  - Ciclopirox (CPX) is a synthetic antifungal drug that is mainly used to treat
      dermatomycoses. The aim of the present study was to determine whether CPX could
      influence Ewing sarcoma progression. The present study suggested that CPX
      treatment may inhibit Ewing sarcoma (ES) progression through Ewing sarcoma
      breakpoint region 1-Friend leukemia integration 1 (EWS-FLI1), a common fusion
      transcript structure in patients with ES. To determine the underlying mechanisms
      of ES progression, cross analysis was conducted on three high-throughput genome
      or transcript me datasets from the Gene Expression Omnibus. The results indicated
      that CPX may inhibit ES growth by affecting vasculature development and DNA
      replication. A combination of genome-wide expression and binding profiles
      revealed several potential targets for CPX in ES, including collagen type I
      alpha2 chain, N-myc proto-oncogene and transforming growth factor beta1, which
      contained significantly enriched binding peaks of FLI1. In addition, network
      analysis, including a protein-protein interaction network and a transcription
      regulatory network, provided further detailed information about the roles of CPX
      in ES. This study may provide a novel solution for ES treatment and may also aid
      in improving its prognosis.

PMID- 29328474
TI  - Inhibition of miR-34a prevents endothelial cell apoptosis by directly targeting
      HDAC1 in the setting of atherosclerosis.
AB  - Despite recent medical advances, atherosclerosis is a global burden accounting
      for numerous mortalities and hospital admissions. MicroRNAs (miRNAs/miRs)
      regulate cardiovascular biology and disease, but the role of microRNA-34a in
      atherosclerosis remains unclear. In the present study, it was demonstrated that
      miR-34a was highly expressed in atherosclerotic lesions and oxidized low-density
      lipoprotein (Ox-LDL)-treated human aortic endothelial cells (HAECs)
      (atherosclerotic cell model) using reverse transcription-quantitative polymerase
      chain reaction. The expression of histone deacetylase (HDAC) 1 was reduced in
      atherosclerotic lesions and Ox-LDL treated HAECs. TargetScan predicted that HDAC1
      is the potential target of miR-34a and the double-luciferase reporter assay
      confirmed that HDAC1 was directly targeted by miR-34a. Furthermore, miR-34a
      inhibitor significantly enhanced the cell viability of HAECs and the cell
      apoptosis was suppressed. In addition, the expression of apoptotic-related
      proteins was detected by western blotting. The results showed that miR-34a
      inhibitor significantly upregulated B-cell lymphoma 2, procaspase-3, procaspase-9
      and proto-oncogene c-Myc protein expression, and downregulated the expression of
      p21. In contrast, co-transfection of HDAC1-small interfering RNA and miR-34a
      inhibitor eliminated the effects of miR-34a on HAECs. This indicated that miR-34a
      inhibitor promoted cell viability and prevented cell apoptosis of HAECs through
      regulating HDAC1. In conclusion, it was demonstrated that miR-34a promoted
      atherosclerotic formation by modulating the proliferation and apoptosis of HAECs,
      and regulating the expression of apoptosis-related proteins by targeting HDAC1.

PMID- 29328475
TI  - Heat shock protein 27 knockdown using nucleotide-based therapies enhances
      sensitivity to 5-FU chemotherapy in SW480 human colon cancer cells.
AB  - Heat shock protein 27 (Hsp27) is a chaperone protein of low molecular weight that
      is produced in response to various stresses and has a cytoprotective function. In
      the present study we found that there is a strong correlation between sensitivity
      to 5-fluorouracil (5-FU) and the expression of Hsp27 in colorectal cancer.
      Apatorsen is an antisense oligonucleotide that targets Hsp27 and has various
      antitumor effects in some types of cancer, such as bladder and prostate. Although
      several clinical studies are currently studying apatorsen in many malignancies,
      to date no promising results have been reported for colorectal cancer. In the
      present study, we examined the impact of Hsp27 downregulation (via apatorsen) on
      5-FU sensitivity in colon cancer both in vitro and in vivo. In vitro, apatorsen
      significantly decreased the levels of Hsp27 in a dose-dependent manner in human
      colon cancer SW480 cells. A cell proliferation assay revealed that although
      apatorsen did not inhibit tumor growth, it resulted in greater 5-FU sensitivity
      in comparison with treatment with OGX-411 (control). In vivo, intraperitoneal
      injection of apatorsen decreased the levels of Hsp27 in subcutaneous tumors in a
      xenograft mouse model using SW480 cells and enhanced 5-FU sensitivity, compared
      to controls. Although further research is warranted, the present study confirmed
      that concurrent treatment with Hsp27 knockdown using apatorsen and 5-FU could be
      a promising therapy for colon cancer.

PMID- 29328477
TI  - Knockdown of ubiquitin-specific peptidase 39 inhibits the malignant progression
      of human renal cell carcinoma.
AB  - Ubiquitin specific peptidase 39 (USP39) serves important roles in mRNA processing
      and is involved in tumorigenesis of multiple solid malignancies. However, the
      influence and underlying mechanism of USP39 on human renal cell carcinomas (RCC)
      remain to be elucidated. The current study investigated the functional roles of
      USP39 in human RCC cell lines. siRNA-mediated RNA interference was used to
      downregulate USP39 in RCC cells. CCK-8, wound healing and invasion assays were
      performed to assess the proliferative ability and metastatic potential. The cell
      cycle distribution and apoptosis were evaluated by flow cytometry. The activity
      of signaling pathways and the expression of cell cycle-related proteins were
      detected by western blot analysis. The siRNA-directed RNA interference targeting
      USP39 could effectively downregulate the expression level of USP39 in two RCC
      cell lines. Depletion of USP39 by siRNA significantly suppressed cell growth and
      decreased invasive capacity of RCC cells. Silencing of USP39 induced cell
      apoptosis and cell cycle arrest at G2/M phase. Additionally, the expression
      levels of apoptotic and G2/M phase-related proteins were notably decreased
      following depletion of USP39. Mechanistically, downregulation of USP39 blocked
      the activation of Akt and extracellular signal regulated kinase signaling
      pathways in RCC cells. These findings indicate that USP39 may serve as an
      oncogenic factor in RCC and could be a potential therapeutic candidate for human
      RCCs.

PMID- 29328476
TI  - Effect of a synthetic inhibitor of urokinase plasminogen activator on the
      migration and invasion of human cervical cancer cells in vitro.
AB  - As a notable feature of malignant tumors, invasion and metastasis are important
      events in the process of tumor progression. Amiloride, a synthetic inhibitor of
      urokinase plasminogen activator (uPA), is involved in these events. To evaluate
      the therapeutic value of amiloride in cervical cancer, HeLa cells were used as in
      vitro cellular models. The migration and invasion abilities of HeLa cells, in
      addition to the mRNA expression of matriptase, uPA, uPA receptor and 72 kDa type
      IV collagenase (MMP-2), were detected using scratch assays, Transwell chamber
      assays and reverse transcription-quantitative polymerase chain reaction (RT
      qPCR). The results of RT-qPCR demonstrated that the mRNA expression of uPA and
      MMP-2 in HeLa cells was downregulated significantly in a dose-dependent manner
      when incubated with various concentrations of amiloride for 24 h. The migration
      distance of HeLa cells was significantly shorter at 6, 12 and 24 h following
      incubation with amiloride (P<0.01), and there was a positive correlation between
      cell migratory ability and cellular uPA protein expression level (r=0.955,
      P<0.01). The number of HeLa cells that penetrated the Matrigel following
      incubation for 24 h with different concentrations of amiloride decreased
      significantly compared with the control group, indicating that cell invasiveness
      was positively correlated with the protein expression level of uPA in the cells
      (r=0.993, P<0.01). The present study demonstrated that amiloride was able to
      specifically inhibit the mRNA expression levels of uPA in HeLa cells, and
      sequentially downregulate the mRNA expression of downstream MMP-2 in the uPA
      system, thereby suppressing the migratory and invasive ability of HeLa cells.
      Therefore, amiloride may be a promising therapeutic target for the treatment of
      cervical cancer.

PMID- 29328478
TI  - Arctigenin exerts protective effects against myocardial infarction via regulation
      of iNOS, COX-2, ERK1/2 and HO-1 in rats.
AB  - The present study aimed to determine the protective effects of arctigenin against
      myocardial infarction (MI), and its effects on oxidative stress and inflammation
      in rats. Left anterior coronary arteries of Sprague-Dawley rats were ligated, in
      order to generate an acute MI (AMI) model. Arctigenin was administered to AMI
      rats at 0, 50, 100 or 200 umol/kg. Western blotting and ELISAs were performed to
      analyze protein expression and enzyme activity. Arctigenin was demonstrated to
      effectively inhibit the levels of alanine transaminase, creatine kinase-MB and
      lactate dehydrogenase, and to reduce infarct size in AMI rats. In addition, the
      activity levels of malondialdehyde, interleukin (IL)-1beta and IL-6 were
      significantly suppressed, and the levels of glutathione peroxidase, catalase and
      superoxide dismutase were significantly increased by arctigenin treatment.
      Arctigenin treatment also suppressed the protein expression levels of inducible
      nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2) and heme oxygenase 1 (HO
      1), and increased the protein expression levels of phosphorylated-extracellular
      signal-regulated kinase 1/2 (p-ERK1/2) in AMI rats. Overall, the results of the
      present study suggest that arctigenin may inhibit MI, and exhibits antioxidative
      and anti-inflammatory effects through regulation of the iNOS, COX-2, ERK1/2 and
      HO-1 pathways in a rat model of AMI.

PMID- 29328480
TI  - Acylated and unacylated ghrelin inhibit apoptosis in myoblasts cocultured with
      colon carcinoma cells.
AB  - Cancer cachexia is a life-threatening syndrome associated with myofiber damage.
      Tumor factors impair muscle regeneration by promoting myoblast apoptosis. Ghrelin
      is a multifunctional hormone with an anti-apoptotic effect, but its mechanism of
      action is not fully understood. In the present study, we investigated whether the
      coculturing of C2C12 myoblasts with CT26 colon carcinoma cells may induce
      myoblast apoptosis, and whether acylated ghrelin (AG) and unacylated ghrelin
      (UnAG) may exert anti-apoptotic effects. We found that the coculture induced
      myoblast apoptosis and increased tumor necrosis factor (TNF)-alpha concentrations
      in the culture medium. Moreover, the coculture increased c-Jun N-terminal kinase
      (JNK) activity, suppressed Akt activity, increased the mitochondrial Bax/Bcl-2
      ratio, impaired mitochondrial membrane potential (Deltapsim), increased the
      cytosolic cytochrome c levels, and activated the caspase-3/poly (ADP-ribose)
      polymerase (PARP) cascade in myoblasts. We also found that either AG or UnAG
      inhibited these changes. The present study describes a novel in vitro model that
      can be employed to investigate cancer-induced myoblast apoptosis, and our
      findings suggest a possible use for AG and UnAG in treating cancer cachexia.

PMID- 29328479
TI  - The human umbilical cord stem cells improve the viability of OA degenerated
      chondrocytes.
AB  - Osteoarthritis (OA) affects a large number of patients; however, human umbilical
      cord stem cells exhibit therapeutic potential for treating OA. The aim of the
      present study was to explore the interaction between human umbilical cord stem
      cells and degenerated chondrocytes, and the therapeutic potential of human
      umbilical cord stem cells on degenerated chondrocytes. Human umbilical cord
      derived mesenchymal stem cells (hUC-MSCs) were harvested from human umbilical
      cords, and flow cytometry was used to analyze the surface antigen markers, in
      addition, chondrogenic, osteogenic and adipogenic differentiation on the cells
      was investigated. OA cells at P3 were cocultured with hUC-MSCs in a separated co
      culture system, and reverse transcription-polymerase chain reaction and western
      blot were used to evaluate the mRNA, and protein expression of collagen type II
      (Col2), SRY-box 9 (sox-9) and aggrecan. The level of inflammatory cytokines,
      tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-6, IL-10, were analyzed
      by ELISA in the supernatant. hUC-MSCs grow in a fibroblastic shape with stable
      proliferation. hUC-MSCs expressed cluster of differentiation 44 (CD44), CD73,
      CD90, CD105; while did not express CD34, CD45, CD106, CD133. After multi
      induction, hUC-MSCs were able to differatiate into adipogenic, osteogenic and
      chondrogenic lineage. hUC-MSCs inhibited the expression of matrix
      metalloproteinase-13, collagen type X alpha1 chain and cyclooxygenase-2 in OA
      chondrocytes, and enhanced the proliferation of OA chondrocytes, while OA
      chondrocytes stimulated the production of Col2, sox-9 and aggrecan and promoted
      hUC-MSCs differentiate into chondrocytes. Flow cytometry analysis demonstrated
      hUC-MSCs have a predominant expression of stem cell markers, while the
      hematopoietic and endothelial markers were absent. Osteogenic, chondrogenic and
      adipogenic differentiation was observed in certain induction conditions. hUC-MSCs
      improved the proliferation of OA chondrocytes and downregulated the expression of
      inflammatory cytokines, while OA chondrocytes promoted MSCs to differentiate into
      chondrocytes. Taken together, the co-culture of hUC-MSCs and OA chondrocytes may
      provide a therapeutic potential in OA treatment.

PMID- 29328481
TI  - TTF1-NP induces protective autophagy during apoptosis by inhibiting the Akt/mTOR
      pathway and activating JNK in human liver cancer cells.
AB  - TTF1-NP is a flavonoid nanoparticle based on 5,2',4'-trihydroxy-6,7,5'
      trimethoxyflavone (TTF1), which is derived from the medicinal plant Sorbaria
      sorbifolia that grows in the Changbai Mountain. We previously demonstrated
      antitumor effects of TTF1-NP in human hepatoma including induction of apoptosis
      and inhibition of angiogenesis, migration and invasion. Herein, we examined the
      effects of TTF1-NP on autophagy and its relationship with apoptosis, and explored
      potential underlying mechanisms in human hepatoma cell lines. We conducted cell
      viability assays, Annexin V/propidium iodide double staining, Hoechst staining,
      monodansylcadaverine staining, transmission electron microscopy, green
      fluorescent protein-light chain 3 plasmid transfection and western blots. We
      found that TTF1-NP induced apoptosis and autophagy in HepG2 and SMMC-7721 cells.
      Pretreatment with the autophagy inhibitor 3-methyladenine promoted TTF1-NP
      induced apoptosis. TTF1-NP decreased levels of phosphorylated (p)-Akt, p-mTOR and
      p-ERK1/2 and increased p-JNK levels in the two cell lines. Treating cells with
      insulin, SP600125 and U0126 indicated that the Akt/mTOR pathway and JNK were
      involved in TTF1-NP-induced autophagy. Together, these findings suggest that TTF1
      NP induced protective apoptosis-related autophagy by modulating the Akt/mTOR and
      JNK pathways in HepG2 and SMMC-7721 cells. Therefore, autophagy may be a
      potential target for TTF1-NP in human hepatoma therapy.

PMID- 29328482
TI  - Cytisine induces endoplasmic reticulum stress caused by calcium overload in HepG2
      cells.
AB  - Cytisine, a quinolizidine alkaloid, is one of the major bioactive components
      found in the small tree Sophora Alopecuraides L., and is a traditional Chinese
      medicine that is used for treating hepatitis and liver cancer. In the 1960s,
      quinolizidine alkaloids were reported to exhibit inhibitory effects on tumour
      cell proliferation in several types of cancer cells. However, few studies have
      investigated the effect of cytisine on liver cancer. Our team confirmed that
      cytisine induced apoptosis in HepG2 cells via a mitochondrial pathway. The
      primary aim of the present study was to evaluate the endoplasmic reticulum (ER)
      stress caused by calcium overload in cytisine-induced apoptosis in HepG2 cells
      and the molecular mechanisms of this phenomenon. In addition, the present study
      was undertaken to evaluate the expression of alpha7-nAChR when apoptosis was
      induced by cytisine in HepG2 cells. In the present study, transmission electron
      microscopy was used to observe the morphological appearance of HepG2 cells. The
      apoptosis of the cells with cytoplasmic vacuolization was significant under
      electron microscopy. Apoptotic bodies, the expansion of the ER, and swelling of
      mitochondria were observed in the HepG2 cells after cytisine treatment. Flow
      cytometric analysis demonstrated that the apoptosis rate of HepG2 cells was
      upregulated. In addition, the intracellular calcium concentration was detected by
      laser confocal fluorescence microscopy. The laser confocal fluorescence
      microscopy showed that the calcium concentration was increased in a dose
      dependent manner. The activity of caspase-4 was evaluated by an enzyme-linked
      analyser, and the expression levels of CHOP, JNK, p-JNK and alpha7-nAChR were
      assessed via western blot analysis. In the present study, we observed that
      cytisine induced ER stress-inducing factors and CHOP and p-JNK1/2 protein
      expression, and it increased the JNK protein expression in the HepG2 cells.
      Furthermore, alpha7-nAChR protein expression was promoted in a dose-dependent
      manner after cytisine treatment. These findings suggest that cytisine induced the
      ER stress-mediated apoptotic pathway via activation of CHOP, JNK and caspase-4 in
      HepG2 cells, and cytisine is a potential new target compound for nAchRs
      (nicotinic acetylcholine receptors) to treat liver cancer.

PMID- 29328483
TI  - miR-98-5p promotes osteoblast differentiation in MC3T3-E1 cells by targeting CKIP
      1.
AB  - Casein kinase 2-interacting protein 1 (CKIP-1) is a negative regulator for bone
      formation. Previously, using bioinformatics analysis, CKIP-1 has been predicted
      to serve the role of target gene of miR-98-5p. In the present study, the
      potential role of miR-98-5p in regulating osteoblast differentiation through CKIP
      1 was investigated. Following pre-treatment with microRNA (miR)-98-5p agomir or
      miR-98-5p antagomir, MC3T3-E1 cells were cultured in an osteoinductive medium.
      Subsequently, the expression of miR-98-5p, CKIP-1 and levels of osteoblast
      differentiation markers, including alkaline phosphatase, matrix mineralization,
      osteocaicin, collagen type I, runt-related transcription factor 2 and osteopontin
      were assayed. Using a dual-luciferase reporter assay, it was demonstrated that
      CKIP-1 was the target gene of miR-98-5p. miR-98-5p was upregulated as a result of
      treatment with miR-98-5p agomir and promoted osteoblast differentiation.
      Conversely, miR-98-5p antagomir inhibited miR-98-5p expression and osteoblast
      differentiation. miR-98-5p targeted CKIP-1 by binding to its 3'-untranslated
      region. Furthermore, miR-98-5p overexpression decreased the protein levels of
      CKIP-1 and inhibition of miR-98-5p increased the protein levels of CKIP-1. The
      results of the present study indicated that CKIP-1 was a target gene of miR-98-5p
      and that miR-98-5p regulated osteoblast differentiation in MC3T3-E1 cells by
      targeting CKIP-1.

PMID- 29328484
TI  - Additive antitumour effect of D-allose in combination with cisplatin in non-small
      cell lung cancer cells.
AB  - D-allose is a rare sugar which has been shown to have growth inhibitory effects
      in several kinds of malignancies. However, the effect of D-allose on lung cancer
      progression has not been previously studied. To investigate the antitumour effect
      of D-allose in lung cancer cells and its mechanism, human non-small cell lung
      cancer (NSCLC) cell lines (squamous cell carcinomas: EBC1 and VMRC-LCD;
      adenocarcinomas: A549, HI1017, RERF-LC-A1 and NCI-H1975) were treated with D
      allose (50 mM) with or without cisplatin (5 uM). D-allose inhibited cell growth,
      particularly in EBC1 and VMRC-LCD cells. In combination with cisplatin, D-allose
      had a synergistic growth inhibitory effect. D-allose increased the expression of
      thioredoxin interacting protein (TXNIP) at mRNA and protein levels. D-allose
      decreased the proportion of cells in G1 phase and increased those in S and G2/M
      phases. For in vivo experiments, EBC1 cells were inoculated into BALB/c-nu mice.
      After tumourigenesis, D-allose and cisplatin were injected. In this mouse
      xenograft model, additional treatment with D-allose showed a significantly
      greater tumour inhibitory effect compared with cisplatin alone, accompanied by
      lower Ki-67 and higher TXNIP expression. In conclusion, D-allose inhibited NSCLC
      cell proliferation in vitro and tumour progression in vivo. In combination with
      cisplatin, D-allose had an additional antitumour effect. Specifically, increased
      TXNIP expression and subsequent G2/M arrest play a role in D-allose-mediated
      antitumour effects in NSCLC.

PMID- 29328485
TI  - Knockdown of hnRNP A2/B1 inhibits cell proliferation, invasion and cell cycle
      triggering apoptosis in cervical cancer via PI3K/AKT signaling pathway.
AB  - Cervical cancer is currently one of the major threats to women's health. The
      overexpression of heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1) as
      the biomarker has been investigated in various cancers. In our previous study, we
      found that lobaplatin induced apoptosis and cell cycle arrest via downregulation
      of proteins including hnRNP A2/B1 in cervical cancer cells. However, the
      underlying relationship between hnRNP A2/B1 and cervical cancer remained largely
      unknown. hnRNP A2/B1 knock-down in HeLa and CaSki cells was performed by shRNA
      transfection. The expression of hnRNP A2/B1 was detected by western blot and
      Quantitative Real-time PCR. Cell proliferation, migration, invasion and the IC50
      of lobaplatin and irinotecan were determined by MTT assay, Transwell assay, Plate
      colony formation assay and wound healing assay. Flow cytometry was perfomed to
      investigate cell apoptosis and the cell cycle. The expression of PI3K, AKT, p
      AKT, p21, p27, caspase-3, cleaved caspase-3 were revealed by western blot. Nude
      mouse xenograft model was undertaken with HeLa cells and the xenograft tumor
      tissue samples were analyzed for the expression of PCNA and Ki-67 by
      immunohistochemistry and the cell morphology was evaluated by hematoxylin and
      eosin (H&E). Results revealed that hnRNP A2/B1 was successfully silenced in HeLa
      and CaSki cells. hnRNP A2/B1 knock-down significantly induced the suppression of
      proliferation, migration, invasion and also enhancement of apoptosis and reduced
      the IC50 of lobaplatin and irinotecan. The expression of p21, p27 and cleaved
      caspase-3 in shRNA group were significantly upregulated and the expression of p
      AKT was reduced both in vitro and in vivo. The results of immunohistochemistry
      showed that PCNA and Ki-67 were significantly downregulated in vivo. The growth
      of nude mouse xenograft tumor was significantly reduced by hnRNP A2/B1 knock
      down. Taken together, these data indicate that inhibition of hnRNP A2/B1 in
      cervical cancer cells can inhibit cell proliferation and invasion, induce cell
      cycle arrestment and trigger apoptosis via PI3K/AKT signaling pathway. In
      addition, after silencing hnRNP A2/B1 can increase the sensitivity of cervical
      cancer cells to lobaplatin and irinotecan.

PMID- 29328488
TI  - Synthesis and application of 131I-fulvestrant as a targeted radiation drug for
      endocrine therapy in human breast cancer.
AB  - The aim of this study was to label fulvestrant (an endocrine therapy drug for
      breast cancer) with radioiodine and to evaluate the effect of 131I-fulvestrant on
      inhibiting the growth of human breast cancer and its influence on major organs in
      nude mice. Fulvestrant was labeled with radioiodine using a modified chloramine T
      method, and its chemical properties were assessed using traditional methods. The
      binding affinity of 131I-fulvestrant was measured by radioligand binding assays,
      and its antiproliferative activity was determined by MTT assays. The ability of
      131I-fulvestrant to kill MCF-7 and MDA-MB-231 cells was also detected by MTT
      assays. We established MCF-7 cell xenografts in nude mice and monitored tumor
      growth and critical organ function. When the labeling reactions were conducted
      for 5 min at room temperature at pH 7.5, the radiochemical yield of the 131I
      labeling to fulvestrant was 62.34+/-1.8%, the radiochemical purity was 98.6+/
      3.4%, and the half maximal inhibitory concentration (IC50) at 48 h was 35 uCi.
      131I-fulvestrant was stable, and its binding affinity to estrogen receptor
      positive (ER+) MCF-7 cells was also retained. In addition, 131I-fulvestrant
      exhibited similar cytotoxicity in MCF-7 and MDA-MB-231 cells, although MCF-7
      cells showed a slightly more pronounced response. 131I-fulvestrant continuously
      exerted a tumor suppressive effect on MCF-7 cells but not on MDA-MB-231 cells
      (P<0.05). Upon intravenous injection of 131I-fulvestrant into nude mice, the
      radioactivity distribution corresponded to ER expression patterns and was
      primarily confined to the tumor. 131I-fulvestrant exhibited a precise growth
      inhibition effect on MCF-7 breast cancer cells, and its effects on general
      conditions of nude mice and their major organs were manageable. Therefore,
      radioiodine labeling of fulvestrant was successful and could be used to develop
      novel drugs for breast cancer by superimposing the benefits of radiotherapy and
      endocrine therapy.

PMID- 29328487
TI  - Combination of gemcitabine and erlotinib inhibits recurrent pancreatic cancer
      growth in mice via the JAK-STAT pathway.
AB  - Compared to single gemcitabine treatment, the combination of gemcitabine and
      erlotinib has shown effective response in patients with locally advanced or
      metastatic pancreatic cancer. However, the combination therapy has not proven
      effective in patients with pancreatic cancer after R0 or R1 resection. In the
      present study, a nude mice model of orthotopic xenotransplantation after tumor
      resection was established using pancreatic cancer cell lines, BxPC-3 and PANC-1.
      Mice were divided in four groups (each with n=12) and were treated as follows:
      the control group received a placebo via intraperitoneal injection (i.p.), while
      the other three groups were treated with gemcitabine (50 mg/kg i.p., twice a
      week), erlotinib (50 mg/kg oral gavage, once every three days), and combined
      treatment of gemcitabine and erlotinib, respectively. The treatment lasted for 21
      days, after which all mice were sacrificed and tumors were examined ex vivo. We
      determined that the combination of gemcitabine and erlotinib inhibited recurrent
      tumor growth and induced apoptosis in vivo by downregulating phosphorylation
      levels of JAKs and STATs, which in turn downregulated the downstream proteins HIF
      1alpha and cyclin D1, and upregulated caspase-9 and caspase-3 expression. To sum
      up, the combination of gemcitabine with erlotinib was effective in treating
      patients with pancreatic cancer after R0 or R1 resection.

PMID- 29328489
TI  - Antibody-nanoparticle conjugate constructed with trastuzumab and nanoparticle
      albumin-bound paclitaxel for targeted therapy of human epidermal growth factor
      receptor 2-positive gastric cancer.
AB  - Gastric cancer (GC) is the most lethal malignancy in the digestive system. This
      study investigated an antibody-nanoparticle conjugate (ANC) constructed with
      trastuzumab (Herceptin(r)) and nanoparticle albumin-bound paclitaxel (nab
      paclitaxel, Abraxane(r)) (trastuzumab/nab-paclitaxel) as a novel strategy of
      targeted therapy for human epidermal growth factor receptor 2 (HER2) positive GC.
      The ANC was fabricated with trastuzumab and nab-paclitaxel by a 'one-step'
      synthesis using EDC/NHS. In vitro antitumor efficacy was evaluated by cell
      viability, apoptosis rate and cell cycle of HER2-positive GC NCI-N87 cells and
      compared with paclitaxel (Taxol(r)), nab-paclitaxel and trastuzumab/nab
      paclitaxel. In addition, GC xenograft models were established to evaluate
      antitumor efficacy in vivo. These results demonstrated that trastuzumab/nab
      paclitaxel was spherical with a suitable size (139.18+/-32.06 nm). The half
      maximal inhibitory concentration (IC50) for NCI-N87 cells was 0.24+/-0.08, 0.13+/
      0.03 and 0.048+/-0.01 ug/ml of paclitaxel, nab-paclitaxel and trastuzumab/nab
      paclitaxel, respectively. Compared with paclitaxel and nab-paclitaxel,
      trastuzumab/nab-paclitaxel could induce a higher rate of apoptosis and
      significant G2/M arrest. At 4 weeks after treatment, tumor-bearing mice had a
      mean tumor volume of 233+/-24 mm3 treated by trastuzumab/nab-paclitaxel, 559+/-97
      mm3 by nab-paclitaxel, 871+/-94 mm3 by paclitaxel and 1,576+/-190 mm3 by PBS as
      control, respectively, which showed that trastuzumab/nab-paclitaxel could surpass
      nab-paclitaxel and paclitaxel in antitumor effect. Furthermore, the NIR imaging
      indicated that trastuzumab/nab-paclitaxel labeled by NIR-797 could more precisely
      focus on tumor regions. In conclusion, trastuzumab/nab-paclitaxel could mediate
      targeted therapy and enhance antitumor efficacy, which could represent a novel
      therapeutic agent for HER2-positive GC.

PMID- 29328486
TI  - miR-873 inhibits colorectal cancer cell proliferation by targeting TRAF5 and
      TAB1.
AB  - MicroRNA-873 (miR-873) has been reported to be dysregulated in a variety of
      malignancies, however, the biological function and underlying molecular mechanism
      of miR-873 in colorectal cancer (CRC) remain unclear. In the present study we
      found that the expression levels of miR-873 were markedly decreased in CRC cell
      lines and tissues from patients. Statistical analysis revealed that miR-873
      expression was inversely correlated with the disease stage of CRC. Kaplan-Meier
      survival analysis revealed that patients with CRC with lower miR-873 expression
      had shorter overall survival rates. Additionally, downregulation of miR-873
      enhanced the proliferation of CRC cells, while upregulation of miR-873 reduced
      this proliferation. Furthermore, we found that tumor necrosis factor (TNF)
      receptor-associated factor 5 (TRAF5) and TGF-beta activated kinase 1 (MAP3K7)
      binding protein 1 (TAB1) were direct targets of miR-873 in CRC cells. A
      luciferase assay revealed that ectopic expression of miR-873 significantly
      reduced nuclear factor kappaB (NF-kappaB) luciferase activity, while ectopic
      expression of miR-873 inhibitor enhanced luciferase activity, suggesting that
      downregulation of miR-873 can activate NF-kappaB signaling. Therefore, our
      findings established a tumor-suppressive role for miR-873 in the inhibition of
      CRC progression, which may be employed as a novel prognostic marker and as an
      effective therapeutic target for CRC.

PMID- 29328491
TI  - MicroRNA-let-7a regulates cell autophagy by targeting Rictor in gastric cancer
      cell lines MGC-803 and SGC-7901.
AB  - miR-let-7a is the most widely studied miRNA, whose functions have been well
      established by scientists in both carcinogenesis and progression of human cancer,
      including gastric cancer (GC). However, to date there is a lack of information
      concerning the relationship between miR-let-7a and cellular autophagy. Using
      western blotting and immunofluorescence, we determined that upregulation of miR
      let-7a led to increased cellular autophagic level, whereas miR-let-7a suppression
      decreased autophagy activity in GC cells. To further elucidate the mechanisms
      underlying this, we screened potential targets of miR-let-7a using bioinformatics
      analyses, validated by a series of assays. Our results indicated that Rptor
      independent companion of mTOR complex 2 (Rictor) was a direct target of miR-let
      7a. In addition, rescue experiments in vitro showed that miR-let-7a promoted
      cellular autophagic level by inhibiting Rictor expression in GC cells.
      Furthermore, as an upstream executor of Akt-mTOR signaling pathway, we found that
      Rictor elaborated its effect on autophagy by phosphorylating Akt and mTOR, and
      this regulatory process could also be mediated by miR-let-7a. Taken together, our
      results present a novel role for miR-let-7a in GC which modulates autophagy by
      targeting Rictor, following the regulation of Akt-mTOR signal pathway.

PMID- 29328490
TI  - Galectin-1 expression in activated pancreatic satellite cells promotes fibrosis
      in chronic pancreatitis/pancreatic cancer via the TGF-beta1/Smad pathway.
AB  - Chronic pancreatitis/pancreatic cancer (CP/PC) is characterized by fibrous
      connective tissue proliferation induced by activated pancreatic stellate cells
      (PSCs). Galectin-1 is upregulated in activated PSCs and is important for the
      continuing activation of PSCs. The aim of this study was to evaluate the effect
      of galectin-1 derived from activated PSCs on the progression of fibrosis in
      CP/PC. To this end, the expression of desmin, alpha-SMA, galectin-1, fibronectin
      and collagen type I in normal pancreatic, CP and PC tissues, as well as
      quiescent/activated PSCs, was investigated. The proliferation rate and migration
      ability of control, galectin-1-overexpressing and galectin-1-silenced PSCs were
      also evaluated, as well as the mRNA and protein expression of fibronectin,
      collagen type I, alpha-SMA, tissue inhibitors of metalloproteinases (TIMP)-1, MMP
      2, Smad2 and TGF-beta1. Furthermore, the effect of adding a TGF-beta1 receptor
      inhibitor on the expression of these proteins was examined. The results revealed
      that the expression profile of desmin, alpha-SMA, galectin-1, fibronectin and
      collagen type I in the normal pancreas was similar to that of quiescent PSCs and
      the expression profile in CP/PC tissues was similar to that of activated PSCs.
      Furthermore, galectin-1-overexpressing PSCs exhibited a significantly higher
      proliferation rate and migration ability, while galectin-1-silenced PSCs
      exhibited a significantly lower proliferation rate and migration ability than the
      control PSCs. The expression of fibronectin, collagen type I, alpha-SMA, MMP-2
      and TIMP-1 was also significantly higher in the galectin-1-overexpressing PSCs
      than the control PSCs and this effect was found to be mediated by the TGF
      beta1/Smad pathway. The trends in the expression of these factors were reversed
      in the galectin-1-silenced PSCs. From these findings, it can be concluded that
      overexpression of galectin-1 promotes PSC activity (proliferation and migration)
      and stimulates fibrosis by increasing extracellular matrix synthesis and
      decreasing the MMP/TIMP ratio via the TGF-beta1/Smad pathway. Thus, galectin-1
      may be a novel candidate for reversing or halting fibrosis progression in CP/PC.

PMID- 29328492
TI  - Exosomes derived from oxidized LDL-stimulated macrophages attenuate the growth
      and tube formation of endothelial cells.
AB  - Oxidized low-density lipoprotein (oxLDL) has a critical role in the development
      of atherosclerosis. The participation of oxLDL-stimulated macrophages has been
      well-established in atherosclerosis, however the underlying mechanisms are
      unclear. Macrophage-derived exosomes are actively released and are involved in
      numerous physiological and pathological processes. However, the function of
      exosomes secreted by oxLDL-stimulated macrophages in atherosclerosis remains
      unknown. Exosomes from oxLDL-treated macrophages and controls were co-cultured
      with endothelial cells and the exosomes were taken up by endocytosis. Cell
      Counting Kit-8 and tube formation assay results revealed that exosomes derived
      from oxLDL-stimulated macrophages reduced the growth and tube formation ability
      of endothelial cells. Suppression of exosomal secretion by oxLDL-stimulated
      macrophages rescued the growth and tube formation ability of endothelial cells.
      Therefore, the results of the present study indicate that oxLDL-stimulated
      macrophages may attenuate the growth and tube formation of endothelial cells, at
      least in part through exosomal transfer. This may provide novel targets for the
      development of atherosclerosis therapeutics.

PMID- 29328493
TI  - Meta-analysis of mRNA expression profiles to identify differentially expressed
      genes in lung adenocarcinoma tissue from smokers and non-smokers.
AB  - Compared to other types of lung cancer, lung adenocarcinoma patients with a
      history of smoking have a poor prognosis during the treatment of lung cancer. How
      lung adenocarcinoma-related genes are differentially expressed between smoker and
      non-smoker patients has yet to be fully elucidated. We performed a meta-analysis
      of four publicly available microarray datasets related to lung adenocarcinoma
      tissue in patients with a history of smoking using R statistical software. The
      top 50 differentially expressed genes (DEGs) in smoking vs. non-smoking patients
      are shown using heat maps. Additionally, we conducted KEGG and GO analyses. In
      addition, we performed a PPI network analysis for 8 genes that were selected
      during a previous analysis. We identified a total of 2,932 DEGs (1,806
      upregulated, 1,126 downregulated) and five genes (CDC45, CDC20, ANAPC7, CDC6,
      ESPL1) that may link lung adenocarcinoma to smoking history. Our study may
      provide new insights into the complex mechanisms of lung adenocarcinoma in
      smoking patients, and our novel gene expression signatures will be useful for
      future clinical studies.

PMID- 29328495
TI  - Fucoidan downregulates insulin-like growth factor-I receptor levels in HT-29
      human colon cancer cells.
AB  - Fucoidan, a sulfated polysaccharide present in brown seaweed, has demonstrated
      anticancer activity in lung, breast, liver and colon cells. The insulin-like
      growth factor (IGF) signaling pathway regulates growth in HT-29 cells through the
      insulin receptor substrate-1 (IRS-1)/phosphatidylinositol 3-kinase (PI3K)/protein
      kinase B (AKT) and Ras/Raf/extracellular signal-regulated kinase (ERK) pathways.
      The aim of the present study was to investigate whether fucoidan downregulates
      the IGF-IR signaling pathway in HT-29 human colon cancer cells. Fucoidan
      treatment (0-1,000 ug/ml) was administered for 24 h in HT-29 cells. First, we
      investigated IRS-1/PI3K/AKT pathway-related protein expression levels following
      treatment with fucoidan (0-500 ug/ml) using western blot analysis. Fucoidan
      significantly inhibited the expression of IGF-IR, PTEN, PI3K and AKT as well as
      their phosphorylated forms (p-IRS-1, p-PI3K and p-AKT). Next, we investigated the
      effects of fucoidan on Ras/Raf/ERK pathway-related protein expression levels in
      HT-29 cells. Fucoidan significantly inhibited the expression of IGF-IR, Shc, Ras,
      SOS, Raf and MEK. HT-29 cells were then incubated in the presence of fucoidan (0
      or 250 ug/ml), and IGF-I (10 nM) was added for 0 to 60 min. Immunoprecipitation
      (IP) experiments showed that fucoidan inhibited IGF-I-induced phosphorylation of
      IGF-IR, PI3K, Shc (IP, IGF-IR), and phosphorylated IRS-1 and PI3K (IP, IRS-1)
      compared to the control group. Western blot analysis showed that fucoidan
      inhibited the expression of IGF-I-induced p-IGF-IR/IGF-IR and p-AKT/AKT, but not
      p-ERK/ERK. In conclusion, the inhibition of cell viability by fucoidan in HT-29
      cells may be due to the downregulation of IGF-IR signaling through the main IRS
      1/PI3K/AKT pathway. Fucoidan also partially impacted Ras/Raf signaling in the
      Ras/Raf/ERK pathway. Therefore, we suggest that fucoidan may be a suitable
      candidate chemopreventive agent in HT-29 colon cancer cells.

PMID- 29328494
TI  - Pterostilbene inhibits reactive oxygen species production and apoptosis in
      primary spinal cord neurons by activating autophagy via the mechanistic target of
      rapamycin signaling pathway.
AB  - Autophagy is an important self-adaptive mechanism that is involved in inhibiting
      reactive oxygen species (ROS) in spinal cord neurons. Pterostilbene, a natural
      plant extract, has been demonstrated to possess antioxidant effects; however, it
      has not yet been investigated whether pterostilbene could activate autophagy and
      protect spinal cord neurons from oxidative stress. In the present study, primary
      spinal cord neurons of Sprague Dawley rats were cultured. Cell counting kit-8
      analysis was used to detect cytotoxicity of pterostilbene. Cells were treated
      with various doses of pterostilbene for 24 and 48 h, respectively, and H2O2 was
      used to induce ROS production. Western blot analysis was performed to assess the
      protein expression of microtubule-associated protein 1 light chain 3 (LC3)-II,
      Beclin-1, p62, p-p70S6K and p-mechanistic target of rapamycin (mTOR).
      Furthermore, the green fluorescent protein (GFP)-LC3 assay was used to detect the
      level of autophagy level and activation mechanism. 2',7'-Dichlorofluorescin
      diacetate and MitoSOX Red staining were used to detect ROS production, and
      Terminal deoxynucleotidyl-transferase-mediated dUTP nick end labelling assay was
      used to analyze apoptosis percentage. ATG5 small interfering (si)RNA transfection
      was used to analyze the involvement of autophagy. A dose-dependent increase in
      the expression of LC3-II and Beclin-1, as well as the p62 decline, were observed
      in the pterostilbene-treated neurons; however, p-p70S6K and p-mTOR expression was
      inhibited by pterostilbene. Pterostilbene increased the expression of LC3-II in
      H2O2-treated cells, and GFP-LC3 analysis demonstrated an increased number of
      autophagosomes. Furthermore, pterostilbene significantly inhibited the ROS
      production and apoptosis induced by H2O2; however, ATG5 siRNA transfection
      significantly reversed the protection of pterostilbene. These results indicate
      that pterostilbene may inhibit the ROS production and apoptosis in spinal cord
      neurons by activating autophagy via the mTOR signaling pathway.

PMID- 29328497
TI  - Identification of theranostic biomarkers to improve the stratification of
      patients with pediatric liver cancer: Opportunities and challenges.

PMID- 29328496
TI  - Hypotension Risk Based on Vasoactive Agent Discontinuation Order in Patients in
      the Recovery Phase of Septic Shock.
AB  - STUDY OBJECTIVES: Patients with septic shock often require vasoactive agents for
      hemodynamic support; however, the optimal approach to discontinuing these agents
      once patients reach the recovery phase is currently unknown. The objective of
      this evaluation was to compare the incidence of hypotension within 24 hours based
      on the discontinuation order of norepinephrine (NE) and vasopressin (AVP) in
      patients in the recovery phase of septic shock. DESIGN: Retrospective cohort
      study. SETTING: The medical, surgical, and neurosciences intensive care units
      (ICUs) at a large tertiary care academic medical center. PATIENTS: A total of 585
      adults in the recovery phase of septic shock who received fixed-dose AVP for at
      least 6 hours as an adjunct to NE between September 2011 and August 2015 were
      included. Of these patients, 155 had AVP discontinued first, and 430 had NE
      discontinued first. MEASUREMENTS AND MAIN RESULTS: Hypotension was evaluated
      during the 24-hour period after discontinuation of the first vasoactive agent and
      was defined as mean arterial pressure less than 60 mm Hg with one or more of the
      following interventions: increased remaining vasoactive agent dose by 25%,
      reinstitution of the discontinued agent, or administration of at least 1 L of
      fluid bolus. Time to hypotension was evaluated with survival analysis, and risk
      of hypotension was evaluated with multivariable Cox proportional hazards
      regression. No significant difference between groups was noted in the incidence
      of hypotension within 24 hours (55% in the AVP discontinued first group vs 50% in
      the NE discontinued first group, p=0.28) or ICU mortality (45.2% vs 40.0%,
      p=0.26). After adjustment for baseline factors with multivariable Cox
      proportional hazards regression, having AVP discontinued first was independently
      associated with an increased risk of hypotension with a time-varying effect that
      decreased over time (HR(t) = e[1.16-0.08*t] , p<0.001). CONCLUSION: In patients
      recovering from septic shock treated with concomitant AVP and NE, no significant
      difference was noted in the incidence of hypotension based on discontinuation
      order of these agents.

PMID- 29328498
TI  - A UPLC-MS/MS method for simultaneous determination of five flavonoids from
      Stellera chamaejasme L. in rat plasma and its application to a pharmacokinetic
      study.
AB  - Stellera chamaejasme L. has been used as a traditional Chinese medicine for the
      treatment of scabies, tinea, stubborn skin ulcers, chronic tracheitis, cancer and
      tuberculosis. A sensitive and selective ultra-high liquid chromatography-tandem
      mass spectrometry (UPLC-MS/MS) method was developed and validated for the
      simultaneous determination of five flavonoids (stelleranol, chamaechromone,
      neochamaejasmin A, chamaejasmine and isochamaejasmin) of S. chamaejasme L. in rat
      plasma. Chromatographic separation was accomplished on an Agilent Poroshell 120
      EC-C18 column (2.1 * 100 mm, 2.7 MUm) with gradient elution at a flow rate of 0.4
      mL/min and the total analysis time was 7 min. The analytes were detected using
      multiple reaction monitoring in positive ionization mode. The samples were
      prepared by liquid-liquid extraction with ethyl acetate. The UPLC-MS/MS method
      was validated for specificity, linearity, sensitivity, accuracy and precision,
      recovery, matrix effect and stability. The validated method exhibited good
      linearity (r >= 0.9956), and the lower limits of quantification ranged from 0.51
      to 0.64 ng/mL for five flavonoids. The intra- and inter-day precision were both
      <10.2%, and the accuracy ranged from -11.79 to 9.21%. This method was
      successfully applied to a pharmacokinetic study of five flavonoids in rats after
      oral administration of ethyl acetate extract of S. chamaejasme L.

PMID- 29328499
TI  - MAIT cells are chronically activated in patients with autoimmune liver disease
      and promote profibrogenic hepatic stellate cell activation.
AB  - : Autoimmune liver diseases (AILDs) are chronic liver pathologies characterized
      by fibrosis and cirrhosis due to immune-mediated liver damage. In this study, we
      addressed the question whether mucosal-associated invariant T (MAIT) cells,
      innate-like T cells, are functionally altered in patients with AILD and whether
      MAIT cells can promote liver fibrosis through activation of hepatic stellate
      cells (HSCs). We analyzed the phenotype and function of MAIT cells from AILD
      patients and healthy controls by multicolor flow cytometry and investigated the
      interaction between human MAIT cells and primary human hepatic stellate cells
      (hHSCs). We show that MAIT cells are significantly decreased in peripheral blood
      and liver tissue of patients with AILD. Notably, MAIT cell frequency tended to
      decrease with increasing fibrosis stage. MAIT cells from AILD patients showed
      signs of exhaustion, such as impaired interferon-gamma (IFN-gamma) production and
      high ex vivo expression of the activation and exhaustion markers CD38, HLA-DR,
      and CTLA-4. Mechanistically, this exhausted state could be induced by repetitive
      stimulation of MAIT cells with the cytokines interleukin (IL)-12 and IL-18,
      leading to decreased IFN-gamma and increased exhaustion marker expression. Of
      note, repetitive stimulation with IL-12 further resulted in expression of the
      profibrogenic cytokine IL-17A by otherwise exhausted MAIT cells. Accordingly,
      MAIT cells from both healthy controls and AILD patients were able to induce an
      activated, proinflammatory and profibrogenic phenotype in hHSCs in vitro that was
      partly mediated by IL-17. CONCLUSION: Our data provide evidence that MAIT cells
      in AILD patients have evolved towards an exhausted, profibrogenic phenotype and
      can contribute to the development of HSC-mediated liver fibrosis. These findings
      reveal a cellular and molecular pathway for fibrosis development in AILD that
      could be exploited for antifibrotic therapy. (Hepatology 2018;68:172-186).

PMID- 29328500
TI  - LAIR-1 shedding from human fibroblast-like synoviocytes in rheumatoid arthritis
      following TNF-alpha stimulation.
AB  - This study examined the expression of the inhibitory receptor, leucocyte
      associated immunoglobulin (Ig)-like receptor-1 (LAIR-1) in fibroblast-like
      synoviocytes (FLS) in rheumatoid arthritis (RA) patients to investigate its
      potential role in the modulation of inflammatory cytokines, matrix
      metalloproteinases (MMPs) and invasiveness of synoviocytes. LAIR-1 expression in
      synovial tissues from RA patients, osteoarthritis patients and healthy donors was
      analysed by immunohistochemistry. The membrane-bound form (mLAIR-1) was detected
      by flow cytometry. Factors involved in inflammation and MMP activity in FLS were
      analysed by quantitative polymerase chain reaction (qPCR). LAIR-1 expression was
      higher in the synovia of the RA patients than those of the osteoarthritis
      patients. Co-immunostaining of vimentin/LAIR-1 demonstrated that LAIR-1 was
      localized mainly in FLS in the RA patients. Surprisingly, primary FLS isolated
      from the RA patients had low levels of mLAIR-1 expression, with cytoplasmic
      distribution. The extracellular domain of LAIR-1 was shed from the cell surface
      in response to tumour necrosis factor (TNF)-alpha, and this process could be
      blocked by serine protease inhibitors. Additional experiments indicated that LAIR
      1 over-expression reduced FLS invasion considerably, which reduced simultaneously
      the mRNA levels of interleukin (IL)-6, IL-8 and MMP-13 in the presence of TNF
      alpha. Our study demonstrated that LAIR-1 is an anti-inflammatory molecule, and
      was up-regulated in FLS in the RA patients; however, cell-surface LAIR-1 could be
      shed from cells in the inflammatory microenvironment in RA. This may weaken the
      interaction of LAIR-1 with its ligand, thus reducing the anti-inflammatory
      effects of LAIR-1. These findings suggested that LAIR-1 may be an important
      factor involved in the mediation of the progressive joint destruction in RA.

PMID- 29328501
TI  - Cognitive control functions in individuals with obesity with and without binge
      eating disorder.
AB  - OBJECTIVE: Deficits in cognitive control are thought to contribute to the
      maintenance of obesity (OB). Cognitive control is referred to as impulsivity and
      binge-eating disorder (BED) is characterized by high levels of impulsivity. The
      present study sought to elucidate which cognitive control functions differentiate
      between severe OB with and without BED also taking into account hunger as a
      moderating factor. METHOD: The study included 48 individuals with OB and BED (OB
      + BED), 48 individuals with OB and no BED (OB - BED) and 48 normal-weight
      controls (NWC). Hunger was systematically manipulated: participants were
      instructed to refrain from eating before testing and received either a liquid
      meal or flavored water. Then, a comprehensive test battery was administered
      including a food-related go/no-go task and several subtests from the CANTAB.
      RESULTS: There were no differences between the groups with regard to food-related
      response inhibition. However, while manipulating hunger had no impact on
      performance in the go/no-go task, self-reported hunger significantly influenced
      task performance by increasing inhibition deficits to high-caloric stimuli in OB
      + BED. With regard to general cognitive control functions, we found that deficits
      in attention and impulse control in decision-making distinguished OB from NWC,
      while reversal learning and risk taking in decision-making appeared to be
      relevant factors when distinguishing OB + BED from OB - BED. DISCUSSION: Our
      results indicate that self-reported hunger differentially affected food-related
      response inhibition. Group differences in general cognitive control functions
      were limited to attention, reversal learning, and decision-making. Future
      research needs to account for other possible moderating factors, such as mood,
      food craving, or stress.

PMID- 29328502
TI  - Hepatocellular carcinoma-related cyclin D1 is selectively regulated by autophagy
      degradation system.
AB  - : Dysfunction of degradation machineries causes cancers, including hepatocellular
      carcinoma (HCC). Overexpression of cyclin D1 in HCC has been reported. We
      previously reported that autophagy preferentially recruits and degrades the
      oncogenic microRNA (miR)-224 to prevent HCC. Therefore, in the present study, we
      attempted to clarify whether cyclin D1 is another oncogenic factor selectively
      regulated by autophagy in HCC tumorigenesis. Initially, we found an inverse
      correlation between low autophagic activity and high cyclin D1 expression in
      tumors of 147 HCC patients and three murine models, and these results taken
      together revealed a correlation with poor overall survival of HCC patients,
      indicating the importance of these two events in HCC development. We found that
      increased autophagic activity leads to cyclin D1 ubiquitination and selective
      recruitment to the autophagosome (AP) mediated by a specific receptor,
      sequestosome 1 (SQSTM1), followed by fusion with lysosome and degradation.
      Autophagy-selective degradation of ubiquitinated cyclin D1 through SQSTM1 was
      confirmed using cyclin D1/ubiquitin binding site (K33-238 R) and phosphorylation
      site (T286A) mutants, lentivirus-mediated silencing autophagy-related 5 (ATG5),
      autophagy-related 7 (ATG7), and Sqstm1 knockout cells. Functional studies
      revealed that autophagy-selective degradation of cyclin D1 plays suppressive
      roles in cell proliferation, colony, and liver tumor formation. Notably, an
      increase of autophagic activity by pharmacological inducers (amiodarone and
      rapamycin) significantly suppressed tumor growth in both the orthotopic liver
      tumor and subcutaneous tumor xenograft models. Our findings provide evidence of
      the underlying mechanism involved in the regulation of cyclin D1 by selective
      autophagy to prevent tumor formation. CONCLUSION: Taken together, our data
      demonstrate that autophagic degradation machinery and the cell-cycle regulator,
      cyclin D1, are linked to HCC tumorigenesis. We believe these findings may be of
      value in the development of alternative therapeutics for HCC patients.
      (Hepatology 2018;68:141-154).

PMID- 29328503
TI  - Challenges and Opportunities With Oncology Drug Development in China.
AB  - Cancer is a growing public health problem in China. Despite the high unmet
      medical need of patients with cancer in China, oncology drug approvals have
      historically lagged behind those in the West, mainly the United States and
      Europe. China is currently undertaking regulatory reforms at a fast pace in order
      to mitigate this lag.

PMID- 29328504
TI  - Myotonic dystrophy patient preferences in patient-reported outcome measures.
AB  - INTRODUCTION: When preparing for clinical trials in myotonic dystrophy type-1
      (DM1), it is important that researchers develop and identify patient-reported
      outcome measures with good measurement properties. METHODS: Fifty-two DM1
      patients enrolled in 2 clinical studies completed the Myotonic Dystrophy Health
      Index (MDHI), 36-Item Short Form Health Survey (version 2; SF-36v2),
      Individualized Neuromuscular Quality of Life questionnaire (INQoL), and a
      questionnaire comparing the relevance, usability, overall preference, and
      perceived responsiveness of each measure. The associations between instrument
      scores and physical function, genetic test results, and employment status were
      examined. RESULTS: The MDHI was preferred over the INQoL in 13 of 13 areas and
      was preferred over the SF-36v2 in 9 of 13 areas. The MDHI was the only score that
      was associated with participant employment status, CTG repeat length, and the 3
      measurements of clinical function. DISCUSSION: The MDHI correlates well with
      physical function and is viewed favorably by participants in DM1 clinical
      studies. Muscle Nerve, 2018.

PMID- 29328506
TI  - Underuse of Vitamin K Antagonist and Direct Oral Anticoagulants for Stroke
      Prevention in Patients With Atrial Fibrillation: A Contemporary Review.
AB  - Atrial fibrillation (AF) is a leading cause of stroke. Oral anticoagulant (OAC)
      therapy can significantly reduce the risk of stroke in patients with AF, but
      underuse of OACs for stroke prevention continues to be a serious clinical
      problem, with significant deleterious impact on outcomes. We review the studies
      demonstrating OAC underutilization and evaluating strategies for promoting the
      increased use of OAC therapy for stroke prevention in nonvalvular AF (NVAF)
      patients, including in special patient populations.

PMID- 29328505
TI  - Substance P as a putative efferent transmitter mediates GABAergic inhibition in
      mouse taste buds.
AB  - BACKGROUND AND PURPOSE: Capsaicin-mediated modulation of taste nerve responses is
      thought to be produced indirectly by the actions of neuropeptides, for example,
      CGRP and substance P (SP), on taste cells implying they play a role in taste
      sensitivity. During the processing of gustatory information in taste buds, CGRP
      shapes peripheral taste signals via serotonergic signalling. The underlying
      assumption has been that SP exerts its effects on taste transmitter secretion in
      taste buds of mice. EXPERIMENTAL APPROACH: To test this assumption, we
      investigated the net effect of SP on taste-evoked ATP secretion from mouse taste
      buds, using functional calcium imaging with CHO cells expressing high-affinity
      transmitter receptors as cellular biosensors. KEY RESULTS: Our results showed
      that SP elicited PLC activation-dependent intracellular Ca2+ transients in taste
      cells via neurokinin 1 receptors, most likely on glutamate-aspartate transporter
      expressing Type I cells. Furthermore, SP caused Type I cells to secrete GABA.
      CONCLUSION AND IMPLICATIONS: Combined with the recent findings that GABA
      depresses taste-evoked ATP secretion, the current results indicate that SP
      elicited secretion of GABA, which provided negative feedback onto Type II
      (receptor) cells to reduce taste-evoked ATP secretion. These findings are
      consistent with a role for SP as an inhibitory transmitter that shapes the
      peripheral taste signals, via GABAergic signalling, during the processing of
      gustatory information in taste buds. Notably, the results suggest that SP is
      intimately associated with GABA in mammalian taste signal processing and
      demonstrate an unanticipated route for sensory information flow within the taste
      bud.

PMID- 29328508
TI  - Serologic responses and effectiveness of hepatitis A vaccination among human
      immunodeficiency virus-positive individuals during the outbreak of acute
      hepatitis A.
AB  - : Outbreaks of hepatitis A virus (HAV) infection have been occurring among men
      who have sex with men in the Asia-Pacific region, the United States, and several
      European countries since June 2015 and recently among persons who are homeless
      and use illicit drugs in the United States. We evaluated the serologic responses
      and effectiveness of HAV vaccination in human immunodeficiency virus (HIV)
      positive individuals during the outbreak in Taiwan. From June 1, 2015, to
      September 30, 2016, anti-HAV immunoglobulin G was prospectively determined among
      all HIV-positive individuals. We prospectively observed 1,533 HAV-seronegative,
      HIV-positive individuals (94.1% being men who have sex with men with a median
      cluster of differentiation 4 (CD4) count of 550 cells/MUL) who were advised to
      receive two doses of HAV vaccine administered 6 months apart. Of them, 1,001
      individuals (65.3%) received at least one dose of HAV vaccine during the study
      period and 532 (34.7%) declined to receive vaccine. The primary endpoints were
      serologic response at weeks 28-36 and acquisition of HAV infection during follow
      up. The incidence rate of acute HAV infection was 3.7 and 99.3 per 1,000 person
      years of follow-up in the vaccinated and unvaccinated groups, respectively,
      resulting in a vaccine effectiveness of 96.3%. At weeks 28-36, the seroconversion
      rates were 63.8% and 93.7% in the intention-to-treat and per-protocol analyses,
      respectively. The factors associated with seroconversion at weeks 28-36 were
      younger age (per 1-year decrease, adjusted odds ratio, 1.08; 95% confidence
      interval, 1.02-1.12) and undetectable plasma HIV RNA load (adjusted odds ratio,
      3.19; 95% confidence interval, 1.32-7.68). CONCLUSION: During the outbreak of
      acute hepatitis A, two-dose HAV vaccination is effective at preventing HAV
      infection among HIV-positive individuals receiving combination antiretroviral
      therapy; our data highlight the importance of HAV serologic screening and
      vaccination to prevent outbreaks of acute hepatitis A in at-risk populations.
      (Hepatology 2018;68:22-31).

PMID- 29328507
TI  - Genetics of immune-mediated inflammatory diseases.
AB  - Immune-mediated inflammatory diseases (IMIDs) are characterized by dysregulation
      of the normal immune response, which leads to inflammation. Together, they
      account for a high disease burden in the population, given that they are usually
      chronic conditions with associated co-morbidities. Examples include systemic
      lupus erythematosus, rheumatoid arthritis, Crohn's disease and type 1 diabetes.
      Since the advent of genome-wide association studies, evidence of considerable
      genetic overlap in the loci predisposing to a wide range of IMIDs has emerged.
      Understanding the genetic risk and extent of genetic overlap between IMIDs may
      help to determine which genes control which aspects of the different diseases; it
      may identify potential novel therapeutic targets for a number of these
      conditions, and/or it may facilitate repurposing existing therapies developed
      originally for different conditions. The findings show that autoantibody-mediated
      autoimmune diseases cluster more closely with each other than autoantibody
      negative diseases such as psoriasis, psoriatic arthritis, Crohn's disease and
      ankylosing spondylitis which, instead, form a seronegative genetic cluster. The
      genetic clustering largely mirrors the known response to existing biological
      therapies, but apparent anomalies in treatment response are discussed.

PMID- 29328509
TI  - High refuge availability on coral reefs increases the vulnerability of reef
      associated predators to overexploitation.
AB  - Refuge availability and fishing alter predator-prey interactions on coral reefs,
      but our understanding of how they interact to drive food web dynamics, community
      structure and vulnerability of different trophic groups is unclear. Here, we
      apply a size-based ecosystem model of coral reefs, parameterized with empirical
      measures of structural complexity, to predict fish biomass, productivity and
      community structure in reef ecosystems under a broad range of refuge availability
      and fishing regimes. In unfished ecosystems, the expected positive correlation
      between reef structural complexity and biomass emerges, but a non-linear effect
      of predation refuges is observed for the productivity of predatory fish. Reefs
      with intermediate complexity have the highest predator productivity, but when
      refuge availability is high and prey are less available, predator growth rates
      decrease, with significant implications for fisheries. Specifically, as fishing
      intensity increases, predators in habitats with high refuge availability exhibit
      vulnerability to over-exploitation, resulting in communities dominated by
      herbivores. Our study reveals mechanisms for threshold dynamics in predators
      living in complex habitats and elucidates how predators can be food-limited when
      most of their prey are able to hide. We also highlight the importance of nutrient
      recycling via the detrital pathway, to support high predator biomasses on coral
      reefs.

PMID- 29328510
TI  - A multidimensional assessment of the burden of psoriasis: results from a
      multinational dermatologist and patient survey.
AB  - BACKGROUND: Psoriasis is a chronic, immune-mediated disease, characterized by
      symptoms that include itching and skin pain and is often associated with
      comorbidities. Patients have a substantial detriment to quality of life (QoL) and
      work productivity with associated cost burden. OBJECTIVES: To investigate the
      incremental burden of comorbidities, itch and affected body areas among systemic
      eligible patients with psoriasis, using a multinational survey of dermatologists
      and their patients with psoriasis. METHODS: Multinational data from the Growth
      from Knowledge (GfK) Disease Atlas Global Real-World Evidence program were used.
      Eligible patients were identified as those who were currently having or had ever
      had moderate-to-severe psoriasis, and must have been receiving prescription
      treatments at the time of the survey. Multivariable regression analyses were
      conducted to assess the incremental burden among psoriasis patients with physical
      and psychological comorbidities, itch and affected visible and sensitive body
      areas vs. psoriasis patients without these conditions, respectively. RESULTS: The
      study enrolled 3821 patients with psoriasis, from nine countries, with an average
      Psoriasis Area and Severity Index score of 6.4. The presence of comorbidities was
      associated with a significant increase in the likelihood of skin pain, lower QoL,
      greater work impairment and increased usage of medical resources (except in
      psoriasis patients with obesity and type 2 diabetes). Psoriasis patients
      suffering from itch and those with visible and sensitive affected body areas also
      had impaired QoL vs. those without these conditions. CONCLUSIONS: Psoriasis
      patients with physical and psychological comorbidities, itch and affected visible
      and sensitive body areas had lower QoL and greater work impairment compared to
      those without these conditions.

PMID- 29328512
TI  - Economy of scale: third partner strengthens a keystone ant-plant mutualism.
AB  - While foundation species can stabilize ecosystems at landscape scales, their
      ability to persist is often underlain by keystone interactions occurring at
      smaller scales. Acacia drepanolobium is a foundation tree, comprising >95% of
      woody cover in East African black-cotton savanna ecosystems. Its dominance is
      underlain by a keystone mutualistic interaction with several symbiotic ant
      species in which it provides housing (swollen thorns) and carbohydrate-rich
      nectar from extra-floral nectaries (EFN). In return, it gains protection from
      catastrophic damage from mega-herbivores. Crematogaster mimosae is the
      ecologically dominant symbiotic ant in this system, also providing the highest
      protection services. In addition to tending EFN, C. mimosae tend scale insects
      for carbohydrate-rich honeydew. We investigated the role of scale insects in this
      specialized ant-plant interaction. Specifically, does this putatively redundant
      third partner strengthen the ant-plant mutualism by making the ant a better
      protector of the tree? Or does it weaken the mutualism by being costly to the
      tree while providing no additional benefit to the ant-plant mutualism? We coupled
      observational surveys with two scale-manipulation experiments and found evidence
      that this third partner strengthens the ant-plant mutualism. Trees with scale
      insects experimentally removed experienced a 2.5X increase in elephant damage
      compared to trees with scale insects present over 10 months. Reduced protection
      was driven by scale removal causing a decrease in ant colony size and per capita
      baseline activity and defensive behavior. We also found that ants increased scale
      tending and the density of scale insects on trees when EFN were experimentally
      reduced. Thus, in this system, scale insects and EFN are likely complementary,
      rather than redundant, resources with scale insects benefitting ants when EFN
      production is low (such as during annual dry periods in this semi-arid
      ecosystem). This study reveals that a third-partner strengthens an ant-plant
      mutualism that serves to stabilize a whole ecosystem.

PMID- 29328513
TI  - Wide QRS complex tachycardia followed by 2:1 atrioventricular block: What is the
      mechanism?

PMID- 29328511
TI  - Stigma and unmet sexual and reproductive health needs among international migrant
      sex workers at the Mexico-Guatemala border.
AB  - OBJECTIVE: To explore international migrant sex workers' experiences and
      narratives pertaining to the unmet need for and access to sexual and reproductive
      health (SRH) at the Mexico-Guatemala border. METHODS: An inductive qualitative
      analysis was conducted based on ethnographic fieldwork (2012-2015) including
      participant observation and audio-recorded in-depth interviews. The participants
      were female sex workers aged 18 years or older and international migrants working
      at the Mexico-Guatemala border. RESULTS: In total, 31 women were included. The
      greatest areas of unmet need included accessible, affordable, and nonstigmatizing
      access to contraception and treatment of sexually transmitted infections. On both
      sides of the border, poor information about the health systems, services
      affordability, and perceived stigma resulted in barriers to access SRH services,
      with women preferring to access private doctors in their destination country or
      delaying uptake of until their next trip home. Financial barriers prevented women
      from accessing needed services, with most only receiving SRH services in their
      destination country through public health regulations surrounding sex work or as
      urgent care. CONCLUSIONS: There is a crucial need to avoid prioritizing vertical
      disease-specific services and to promote access to rights-based SRH services for
      migrant sex workers in both home and destination settings.

PMID- 29328514
TI  - A systematic review of population pharmacokinetics of valproic acid.
AB  - AIMS: Population pharmacokinetics is an essential tool that helps guide
      individualized dosing regimens. The aims of this systematic review are to provide
      knowledge concerning population pharmacokinetics of valproic acid (VPA) and to
      identify factors influencing VPA pharmacokinetic variability. METHODS: PubMed and
      Embase databases were systematically searched from inception to June, 2017.
      Relevant articles from reference lists were also included. All population
      pharmacokinetic studies of VPA conducted in humans and that employed a nonlinear
      mixed effect modelling approach were included in this review. RESULTS: Twenty-six
      studies were included in this review. Most studies characterized VPA
      pharmacokinetics as a one-compartment model. Three studies reported a two
      compartment model. Body weight, dose and age were significant predictors for VPA
      volume of distribution (Vd ). The estimated Vd for one-compartment models ranged
      from 8.4 to 23.3 l. For two-compartment models, peripheral volumes of
      distribution ranged from 4.08 to 42.1 l. Frequently reported significant
      predictors for VPA clearance (CLVPA ) included body weight, VPA dose, concomitant
      medications, gender and age. The estimated CLVPA ranged from 0.206 to 1.154 l h-1
      and the inter-individual variability ranged from 13.40 to 35.90%. Two studies
      reported population pharmacokinetics/pharmacodynamics of VPA in patients with
      epilepsy. Seventeen studies evaluated the performance of their final models.
      CONCLUSIONS: Significant predictors influencing VPA pharmacokinetics as well as
      model methodologies are highlighted in this review. For clinical application,
      CLVPA could be predicted using body weight, VPA dose, concomitant medications,
      gender or age. For future research, there is a knowledge gap regarding population
      pharmacokinetics/pharmacodynamics of VPA in a population other than epileptic
      patients.

PMID- 29328515
TI  - Magnetic resonance imaging in facioscapulohumeral muscular dystrophy.

PMID- 29328516
TI  - Ultrasonographic demonstration of intraneural neovascularization after
      penetrating nerve injury.
AB  - INTRODUCTION: Hypervascularization of nerves has been shown to be a pathological
      sign in some peripheral nerve disorders, but has not been investigated in nerve
      trauma. METHODS: An observational cohort study was performed of the intraneural
      blood flow of 30 patients (34 nerves) with penetrating nerve injuries, before or
      after nerve reconstruction. All patients underwent electrophysiological
      assessment, and B-mode and color Doppler ultrasonography. RESULTS: Intraneural
      hypervascularization proximal to the site of injury was found in all nerves,
      which was typically marked and had a longitudinal extension of several
      centimeters. In 6 nerves, some blood flow was also present within the injury site
      or immediately distal to the injury. No correlation was found between the degree
      of vascularization and age, size of the scar / neuroma, or degree of
      reinnervation. DISCUSSION: Neovascularization of nerves proximal to injury sites
      appears to be an essential element of nerve regeneration after penetrating nerve
      injuries. Muscle Nerve 57: 994-999, 2018.

PMID- 29328517
TI  - Creeping eruption and eosinophilic folliculitis: Atypical cutaneous larva
      migrans.

PMID- 29328518
TI  - Stevens-Johnson syndrome/toxic epidermal necrolysis overlap in a NSCLC patient
      treated with afatinib.

PMID- 29328519
TI  - Surface modification using the biomimetic method in alumina-zirconia porous
      ceramics obtained by the replica method.
AB  - The modification of biomaterials approved by the Food and Drug Administration
      could be an alternative to reduce the period of use in humans. Porous bioceramics
      are widely used as support structures for bone formation and repair. This
      composite has essential characteristics for an implant, including good mechanical
      properties, high chemical stability, biocompatibility and adequate aesthetic
      appearance. Here, three-dimensional porous scaffolds of Al2 O3 containing 5% by
      volume of ZrO2 were produced by the replica method. These scaffolds had their
      surfaces chemically treated with phosphoric acid and were coated with calcium
      phosphate using the biomimetic method simulated body fluid (SBF, 5*) for 14 days.
      The scaffolds, before and after biomimetic coating, were characterized
      mechanically, morphologically and structurally by axial compression tests,
      scanning electron microscopy, microtomography, apparent porosity, X-ray
      diffractometry, near-infrared spectroscopy, inductively coupled plasma optical
      emission spectroscopy, energy dispersive X-ray spectroscopy and reactivity. The
      in vitro cell viability and formation of mineralization nodules were used to
      identify the potential for bone regeneration. The produced scaffols after
      immersion in SBF were able to induce the nodules formation. These characteristics
      are advantaged by the formation of different phases of calcium phosphates on the
      material surface in a reduced incubation period. (c) 2018 Wiley Periodicals, Inc.
      J Biomed Mater Res Part B: Appl Biomater, 106B: 2615-2624, 2018.

PMID- 29328522
TI  - Cassava flour slurry as a low-cost alternative to commercially available gel for
      obstetrical ultrasound: a blinded non-inferiority trial comparison of image
      quality.
AB  - OBJECTIVE: To evaluate the quality of ultrasound images obtained with cassava
      flour slurry (CFS) compared with conventional gel in order to determine
      objectively whether CFS could be a true low-cost alternative. DESIGN: Blinded non
      inferiority trial. SETTING: Obstetrical ultrasound unit in an academic medical
      centre. POPULATION OR SAMPLE: Women with a singleton pregnancy, undergoing
      anatomy ultrasounds. METHODS: Thirty pregnant women had standard biometry
      measures obtained with CFS and conventional gel. Images were compared side-by
      side in random order by two blinded sonologists and rated for image resolution,
      detail and total image quality using a 10-cm visual analogue scale. Ratings were
      compared using paired t-tests. Participant and sonographer experience was
      measured using five-point Likert scales. MAIN OUTCOME MEASURES: Image resolution,
      detail, and total image quality. Participant experience of gel regarding
      irritation, messiness, and ease of removal. RESULTS: We found no significant
      difference between perceived image quality obtained with CFS (mean = 6.2, SD =
      1.2) and commercial gel (mean = 6.4, SD = 1.2) [t (28) = -1.1; P = 0.3]. Images
      were not rated significantly differently for either reviewer in any measure, any
      standardized image or any view of a specific anatomic structure. All five
      sonographers rated CFS as easy to obtain clear images and easy for patient and
      machine cleanup. Only one participant reported itching with CFS. CONCLUSIONS: CFS
      produces comparable image quality to commercial ultrasound gel. The dissemination
      of these results and the simple CFS recipe could significantly increase access to
      ultrasound for screening, monitoring and diagnostic purposes in resource-limited
      settings. FUNDING: This study was internally funded by our department. TWEETABLE
      ABSTRACT: Low-cost homemade cassava flour slurry creates images equal to
      commercial ultrasound gel, improving access.

PMID- 29328520
TI  - Dysfunctional sarcomere contractility contributes to muscle weakness in ACTA1
      related nemaline myopathy (NEM3).
AB  - OBJECTIVE: Nemaline myopathy (NM) is one of the most common congenital
      nondystrophic myopathies and is characterized by muscle weakness, often from
      birth. Mutations in ACTA1 are a frequent cause of NM (ie, NEM3). ACTA1 encodes
      alpha-actin 1, the main constituent of the sarcomeric thin filament. The
      mechanisms by which mutations in ACTA1 contribute to muscle weakness in NEM3 are
      incompletely understood. We hypothesized that sarcomeric dysfunction contributes
      to muscle weakness in NEM3 patients. METHODS: To test this hypothesis, we
      performed contractility measurements in individual muscle fibers and myofibrils
      obtained from muscle biopsies of 14 NEM3 patients with different ACTA1 mutations.
      To identify the structural basis for impaired contractility, low angle X-ray
      diffraction and stimulated emission-depletion microscopy were applied. RESULTS:
      Our findings reveal that muscle fibers of NEM3 patients display a reduced maximal
      force-generating capacity, which is caused by dysfunctional sarcomere
      contractility in the majority of patients, as revealed by contractility
      measurements in myofibrils. Low angle X-ray diffraction and stimulated emission
      depletion microscopy indicate that dysfunctional sarcomere contractility in NEM3
      patients involves a lower number of myosin heads binding to actin during muscle
      activation. This lower number is not the result of reduced thin filament length.
      Interestingly, the calcium sensitivity of force is unaffected in some patients,
      but decreased in others. INTERPRETATION: Dysfunctional sarcomere contractility is
      an important contributor to muscle weakness in the majority of NEM3 patients.
      This information is crucial for patient stratification in future clinical trials.
      Ann Neurol 2018;83:269-282.

PMID- 29328523
TI  - Improved portal vein venoplasty with an autogenous patch in pediatric living
      donor liver transplantation.
AB  - A stenotic or hypoplastic portal vein (PV) represents a challenge for PV
      reconstruction in pediatric living donor liver transplantation (LDLT). Several PV
      venoplastic techniques have been developed. However, we still seek improved
      venoplastic techniques with better efficacy and compatibility. From June 2016 to
      July 2017, 271 LDLT procedures were performed at the Department of Liver Surgery,
      Renji Hospital. A total of 16 consecutive children with stenotic and sclerotic
      PVs underwent a novel technique-the autogenous PV patch plastic technique. Vessel
      patches were procured from the left branch (LB), or the bifurcation of the right
      branch and LB of the PV in the native liver. Then, the PVs were enlarged by
      suturing the patches along the longitudinal axis from the confluence of the PV
      and coronary vein (CV). In this series, 15/16 achieved good intraoperational PV
      flow, and 1 showed low PV flow but was treated with stent placement. Within a
      median follow-up of 11 months (1-18 months), 15 patients were alive and had
      normal graft function, whereas 1 child died from lung infection 1 month after
      transplantation. No PV complications were detected. In conclusion, the autogenous
      patch venoplasty technique using the PV-CV confluence is simple and safe. This
      novel venoplastic reconstruction technique could serve as a surgical option to
      achieve satisfactory outcomes, especially those with stenotic PV (<4.5 mm) and
      dilated CV (>3.0 mm). Liver Transplantation 2018 AASLD.

PMID- 29328524
TI  - Self-Healing Inside APbBr3 Halide Perovskite Crystals.
AB  - Self-healing, where a modification in some parameter is reversed with time
      without any external intervention, is one of the particularly interesting
      properties of halide perovskites. While there are a number of studies showing
      such self-healing in perovskites, they all are carried out on thin films, where
      the interface between the perovskite and another phase (including the ambient) is
      often a dominating and interfering factor in the process. Here, self-healing in
      perovskite (methylammonium, formamidinium, and cesium lead bromide (MAPbBr3 ,
      FAPbBr3 , and CsPbBr3 )) single crystals is reported, using two-photon microscopy
      to create damage (photobleaching) ~110 um inside the crystals and to monitor the
      recovery of photoluminescence after the damage. Self-healing occurs in all three
      perovskites with FAPbBr3 the fastest (~1 h) and CsPbBr3 the slowest (tens of
      hours) to recover. This behavior, different from surface-dominated stability
      trends, is typical of the bulk and is strongly dependent on the localization of
      degradation products not far from the site of the damage. The mechanism of self
      healing is discussed with the possible participation of polybromide species. It
      provides a closed chemical cycle and does not necessarily involve defect or ion
      migration phenomena that are often proposed to explain reversible phenomena in
      halide perovskites.

PMID- 29328521
TI  - Central vein sign differentiates Multiple Sclerosis from central nervous system
      inflammatory vasculopathies.
AB  - OBJECTIVES: In multiple sclerosis (MS), magnetic resonance imaging (MRI) is a
      sensitive tool for detecting white matter lesions, but its diagnostic specificity
      is still suboptimal; ambiguous cases are frequent in clinical practice. Detection
      of perivenular lesions in the brain (the "central vein sign") improves the
      pathological specificity of MS diagnosis, but comprehensive evaluation of this
      MRI biomarker in MS-mimicking inflammatory and/or autoimmune diseases, such as
      central nervous system (CNS) inflammatory vasculopathies, is lacking. In a
      multicenter study, we assessed the frequency of perivenular lesions in MS versus
      systemic autoimmune diseases with CNS involvement and primary angiitis of the CNS
      (PACNS). METHODS: In 31 patients with inflammatory CNS vasculopathies and 52 with
      relapsing-remitting MS, 3-dimensional T2*-weighted and T2-fluid-attenuated
      inversion recovery images were obtained during a single MRI acquisition after
      gadolinium injection. For each lesion, the central vein sign was evaluated
      according to consensus guidelines. For each patient, lesion count, volume, and
      brain location, as well as fulfillment of dissemination in space MRI criteria,
      were assessed. RESULTS: MS showed higher frequency of perivenular lesions (median
      = 88%) than did inflammatory CNS vasculopathies (14%), without overlap between
      groups or differences between 3T and 1.5T MRI. Among inflammatory vasculopathies,
      Behcet disease showed the highest median frequency of perivenular lesions (34%),
      followed by PACNS (14%), antiphospholipid syndromes (12%), Sjogren syndrome
      (11%), and systemic lupus erythematosus (0%). When a threshold of 50% perivenular
      lesions was applied, central vein sign discriminated MS from inflammatory
      vasculopathies with a diagnostic accuracy of 100%. INTERPRETATION: The central
      vein sign differentiates inflammatory CNS vasculopathies from MS at standard
      clinical magnetic field strengths. Ann Neurol 2018;83:283-294.

PMID- 29328526
TI  - Brain atrophy in multiple sclerosis: How deep must we go?

PMID- 29328525
TI  - Role of sialic acid-containing glycans of matrix metalloproteinase-9 (MMP-9) in
      the interaction between MMP-9 and staphylococcal superantigen-like protein 5.
AB  - Staphylococcal superantigen-like proteins (SSL) show no superantigenic activity
      but have recently been considered to act as immune suppressors. It was previously
      reported that SSL5 bound to P-selectin glycoprotein ligand-1 (PSGL-1) and matrix
      metalloproteinase (MMP)-9, leading to inhibition of leukocyte adhesion and
      invasion. These interactions were suggested to depend on sialic acid-containing
      glycans of MMP-9, but the roles of sialic acids in the interaction between SSL5
      and MMP-9 are still controversial. In the present study, we prepared recombinant
      glutathione S-transferase-tagged SSL5 (GST-SSL5) and analyzed its binding
      capacity to MMP-9 by pull-down assay after various modifications of its
      carbohydrate moieties. We observed that GST-SSL5 specifically bound to MMP-9 from
      a human monocytic leukemia cell line (THP-1 cells) and inhibited its enzymatic
      activity in a concentration-dependent manner. After MMP-9 was treated with
      neuraminidase, its binding activity towards GST-SSL5 was markedly decreased.
      Furthermore, recombinant MMP-9 produced by sialic acid-deficient Lec2 mutant
      cells showed much lower affinity for SSL5 than that produced by wild-type CHO-K1
      cells. Treatment of MMP-9 with PNGase F to remove N-glycan resulted in no
      significant change in the GST-SSL5/MMP-9 interaction. In contrast, the binding of
      GST-SSL5 to MMP-9 secreted from THP-1 cells cultured in the presence of an
      inhibitor for the biosynthesis of O-glycan (benzyl-GalNAc) was weaker than the
      binding of GST-SSL5 to MMP-9 secreted from untreated cells. These results
      strongly suggest the importance of the sialic acid-containing O-glycans of MMP-9
      for the interaction of MMP-9 with GST-SSL5.

PMID- 29328527
TI  - Pruritic papulovesicular dermatosis with reticular hyperpigmentation.

PMID- 29328528
TI  - Evaluation of the use of recombinant human basic fibroblast growth factor in
      combination with negative pressure wound therapy with instillation and dwell time
      in porcine full-thickness wound model.
AB  - NPWT with instillation and dwell time (NPWTi-d), which combines NPWT with wound
      irrigation, has been clinically applied as a more effective treatment than
      conventional NPWT. Commercially available recombinant human basic fibroblast
      growth factor (rh-bFGF) has been demonstrated to be beneficial for use over the
      wound beds. The objective of this study was to evaluate the effectiveness of
      combined treatment with NPWTi-d and rh-bFGF. Six pigs received 12 full-thickness
      excisional skin wounds and were treated with six different treatment groups for
      each pair. The treatment regimens were composed NPWTi-d, NPWT, or advanced wound
      care with or without rh-bFGF. On day 6, the minimum granulation tissue thickness
      and blood vessel number of the group of combined treatment with NPWTi-d and rh
      bFGF spray were significantly greater than that of the control group. Combined
      treatment with NPWTi-d and rh-bFGF spray reads to good granulation tissue
      formation and vascularization for accelerating wound healing.

PMID- 29328530
TI  - Fusing a Planar Group to a pi-Bowl: Electronic and Molecular Structure,
      Aromaticity and Solid-State Packing of Naphthocorannulene and its Anions.
AB  - Molecular and electronic structure, reduction electron transfer and coordination
      abilities of a polycyclic aromatic hydrocarbon (PAH) having a planar naphtho
      group fused to the corannulene bowl have been investigated for the first time
      using a combination of theoretical and experimental tools. A direct comparison of
      naphtho[2,3-a]corannulene (C28 H14 , 1) with parent corannulene (C20 H10 , 2)
      revealed the effect of framework topology change on electronic properties and
      aromaticity of 1. The presence of two reduction steps for 1 was predicted
      theoretically and confirmed experimentally. Two reversible one-electron reduction
      processes with the formal reduction potentials at -2.30 and -2.77 V versus Fc+/0
      were detected by cyclic voltammetry (CV) measurements, demonstrating
      accessibility of the corresponding mono- and dianionic states of 1. The products
      of the singly and doubly reduced napththocorannulene were prepared using chemical
      reduction with Group 1 metals and isolated as sodium and rubidium salts. Their X
      ray diffraction study revealed the formation of "naked" mono- and dianions
      crystallized as solvent-separated ion products with one or two sodium cations as
      [Na+ (18-crown-6)(THF)2 ][C28 H14- ] and [Na+ (18-crown-6)(THF)2 ]2 [C28 H142- ]
      (3?THF and 4?THF, respectively). The dianion of 1 was also isolated as a contact
      ion complex with two rubidium countercations, [{Rb+ (18-crown-6)}2 (C28 H142- )]
      (5?THF). The structural consequences of adding one and two electrons to the
      carbon framework of 1 are compared for 3, 4 and 5. Changes in aromaticity and
      charge distribution stemming from the stepwise electron acquisition are discussed
      based on DFT computational study.

PMID- 29328529
TI  - Hinokitiol ablates myofibroblast activation in precancerous oral submucous
      fibrosis by targeting Snail.
AB  - Oral submucous fibrosis (OSF) is a precancerous condition with symptoms of
      limited mouth opening and areca nut chewing habit has been implicated in its
      pathogenesis. Hinokitiol, a natural tropolone derived from Chamacyparis
      taiwanensis, has been reported to improve oral lichen planus and inhibit various
      cancer cells. Here, we showed that hinokitiol reduced the myofibroblast
      activities in fBMFs and prevented the arecoline-induced transdifferentiation.
      Treatment of hinokitiol dose-dependently downregulated the myofibroblast markers
      as well as various EMT transcriptional factors. In particular, we identified that
      Snail was able to bind to the E-box in the alpha-SMA promoter. Our data suggested
      that exposure of fBMFs to hinokitiol mitigated the hallmarks of myofibroblasts,
      while overexpression of Snail eliminated the effect of hinokitiol. These findings
      revealed that the inhibitory effect of hinokitiol on myofibroblasts was mediated
      by repression of alpha-SMA via regulation of Snail and showed the anti-fibrotic
      potential of hinokitiol in the treatment of OSF.

PMID- 29328531
TI  - Thalamic atrophy in multiple sclerosis: A magnetic resonance imaging marker of
      neurodegeneration throughout disease.
AB  - OBJECTIVE: Thalamic volume is a candidate magnetic resonance imaging (MRI)-based
      marker associated with neurodegeneration to hasten development of neuroprotective
      treatments. Our objective is to describe the longitudinal evolution of thalamic
      atrophy in MS and normal aging, and to estimate sample sizes for study design.
      METHODS: Six hundred one subjects (2,632 MRI scans) were analyzed. Five hundred
      twenty subjects with relapse-onset MS (clinically isolated syndrome, n = 90;
      relapsing-remitting MS, n = 392; secondary progressive MS, n = 38) underwent
      annual standardized 3T MRI scans for an average of 4.1 years, including a 1mm3 3
      dimensional T1-weighted sequence (3DT1; 2,485 MRI scans). Eighty-one healthy
      controls (HC) were scanned longitudinally on the same scanner using the same
      protocol (147 MRI scans). 3DT1s were processed using FreeSurfer's longitudinal
      pipeline after lesion inpainting. Rates of normalized thalamic volume loss in MS
      and HC were compared in linear mixed effects models. Simulation-based sample size
      calculations were performed incorporating the rate of atrophy in HC. RESULTS:
      Thalamic volume declined significantly faster in MS subjects compared to HC, with
      an estimated decline of -0.71% per year (95% confidence interval [CI] = -0.77% to
      -0.64%) in MS subjects and -0.28% per year (95% CI = -0.58% to 0.02%) in HC (p
      for difference = 0.007). The rate of decline was consistent throughout the MS
      disease duration and across MS clinical subtypes. Eighty or 100 subjects per arm
      (alpha = 0.1 or 0.05, respectively) would be needed to detect the maximal effect
      size with 80% power in a 24-month study. INTERPRETATION: Thalamic atrophy occurs
      early and consistently throughout MS. Preliminary sample size calculations appear
      feasible, adding to its appeal as an MRI marker associated with
      neurodegeneration. Ann Neurol 2018;83:223-234.

PMID- 29328532
TI  - Population genomic footprints of host adaptation, introgression and recombination
      in coffee leaf rust.
AB  - Coffee leaf rust, caused by Hemileia vastatrix (Hv), represents the biggest
      threat to coffee production worldwide and ranks amongst the most serious fungal
      diseases in history. Despite a recent series of outbreaks and emergence of
      hypervirulent strains, the population evolutionary history and potential of this
      pathogen remain poorly understood. To address this issue, we used restriction
      site-associated DNA sequencing (RADseq) to generate ~19 000 single nucleotide
      polymorphisms (SNPs) across a worldwide collection of 37 Hv samples. Contrary to
      the long-standing idea that Hv represents a genetically unstructured and
      cosmopolitan species, our results reveal the existence of a cryptic species
      complex with marked host tropism. Using phylogenetic and pathological data, we
      show that one of these lineages (C3) infects almost exclusively the most
      economically valuable coffee species (tetraploids that include Coffea arabica and
      interspecific hybrids), whereas the other lineages (C1 and C2) are severely
      maladapted to these hosts, but successfully infect diploid coffee species.
      Population dynamic analyses suggest that the C3 group may be a recent
      'domesticated' lineage that emerged via host shift from diploid coffee hosts. We
      also found evidence of recombination occurring within this group, which could
      explain the high pace of pathotype emergence despite the low genetic variation.
      Moreover, genomic footprints of introgression between the C3 and C2 groups were
      discovered and raise the possibility that virulence factors may be quickly
      exchanged between groups with different pathogenic abilities. This work advances
      our understanding of the evolutionary strategies used by plant pathogens in agro
      ecosystems with direct and far-reaching implications for disease control.

PMID- 29328534
TI  - Split-thickness skin grafting for reconstruction of auricular skin defects: a
      statistical analysis.
AB  - BACKGROUND AND OBJECTIVES: Surgical reconstruction following the removal of large
      malignant auricular lesions is challenging. While many options for defect closure
      have been described, in the elderly population usually affected flap surgery,
      long anesthesia times, patient compliance, and anticoagulant therapy pose
      additional risks. An alternative quick, simple, and effective method of defect
      closure is therefore highly desirable. The objective of the present study was to
      assess the aesthetic outcome, healing process, complications, and recurrence
      rates associated with unmeshed split-thickness skin grafts (STSGs) used for
      covering large auricular skin defects following cartilage-sparing skin cancer
      removal. PATIENTS AND METHODS: Under local tumescent anesthesia, 32 patients
      received STSGs for defect closure following the removal of malignant cutaneous
      neoplasms of the ear. RESULTS: The average defect size was 8.0 cm2. In all cases,
      complete healing of the recipient site occurred within two weeks. There were no
      major complications. The aesthetic outcome was rated highly by patients as well
      as by the dermatosurgeon involved and two independent plastic surgeons.
      CONCLUSIONS: STSGs are a valid option for closing large auricular skin defects.
      Even large cutaneous tumors of the external ear do not necessarily infiltrate the
      cartilage. Thus, cartilage-sparing tumor resection with subsequent defect closure
      using a STSG is an excellent and quick method associated with high patient
      satisfaction.

PMID- 29328533
TI  - Cobaltocenylidene: A Mesoionic Metalloceno Carbene, Stabilized in a Gold(III)
      Complex.
AB  - Oxidative addition of cobaltoceniumdiazonium bis(hexafluoridophosphate) with
      (pseudo)halide aurates gave gold(III) complexes containing zwitterionic
      cobaltoceniumide as a ligand. Its selenium derivative, cobaltoceniumselenolate,
      was obtained by an electrophilic aromatic substitution reaction of
      iodocobaltocenium iodide with Na2 Se. Spectroscopic and structural data in
      combination with DFT calculations showed that this cobaltocenylidene species is a
      mesoionic carbene quite different from common N-heterocyclic carbenes. Its ligand
      properties (TEP, singlet-triplet gap, nucleophilicity, pi-acidity, Bronsted
      basicity) are in part comparable to those of cyclic (amino)(alkyl/aryl)carbenes.
      Electrochemistry data showed that the mesoionic cobaltoceniumides are more
      electron-rich than their parent ferrocenes. The reversible reduction of the
      tricyanido gold complex appears 50 mV negative of the cobaltocenium/cobaltocene
      couple, whereas that of the selenide derivative is shifted cathodically by 550
      mV.

PMID- 29328535
TI  - An Exceptionally Close, Non-Bonded Hydrogen-Hydrogen Contact with Strong Through
      Space Spin-Spin Coupling.
AB  - Condensation of 1,8,13-tris(mercaptomethyl)triptycene and
      tris(bromomethyl)methane yields an in,in-cyclophane with two inwardly directed
      methine groups. Based on X-ray analysis and DFT and MP2 calculations, the
      hydrogen-hydrogen non-bonded contact distance is estimated to be 1.50-1.53 A.
      Furthermore, the two in-hydrogen atoms show obvious spin-spin coupling with J=2.0
      Hz.

PMID- 29328536
TI  - Rituximab as monotherapy for the treatment of chronic active antibody-mediated
      rejection after kidney transplantation.

PMID- 29328537
TI  - Deracemization of a Racemic Compound by Using Tailor-Made Additives.
AB  - Viedma ripening is a process that combines abrasive grinding of a slurry of
      crystals with solution-phase racemization, resulting in solid-phase
      deracemization. One of the major disadvantages of Viedma ripening is that the
      desired compound needs to crystallize as a racemic conglomerate, accounting for
      only 5-10 % of all chiral molecules. Herein, we show that use of a chiral
      additive causes deracemization under conditions, in which the compound normally
      crystallizes as a racemic compound. Although this concerns a single example, it
      is envisioned that through this new approach the scope of Viedma ripening can be
      significantly expanded.

PMID- 29328538
TI  - Conflict between heterozygote advantage and hybrid incompatibility in
      haplodiploids (and sex chromosomes).
AB  - In many diploid species, the sex chromosomes play a special role in mediating
      reproductive isolation. In haplodiploids, where females are diploid and males
      haploid, the whole genome behaves similarly to the X/Z chromosomes of diploids.
      Therefore, haplodiploid systems can serve as a model for the role of sex
      chromosomes in speciation and hybridization. A previously described population of
      Finnish Formica wood ants displays genome-wide signs of ploidally and sexually
      antagonistic selection resulting from hybridization. Here, hybrid females have
      increased survivorship but hybrid males are inviable. To understand how the
      unusual hybrid population may be maintained, we developed a mathematical model
      with hybrid incompatibility, female heterozygote advantage, recombination and
      assortative mating. The rugged fitness landscape resulting from the co-occurrence
      of heterozygote advantage and hybrid incompatibility results in a sexual conflict
      in haplodiploids, which is caused by the ploidy difference. Thus, whereas
      heterozygote advantage always promotes long-term polymorphism in diploids, we
      find various outcomes in haplodiploids in which the population stabilizes either
      in favour of males, females or via maximizing the number of introgressed
      individuals. We discuss these outcomes with respect to the potential long-term
      fate of the Finnish wood ant population and provide approximations for the
      extension of the model to multiple incompatibilities. Moreover, we highlight the
      general implications of our results for speciation and hybridization in
      haplodiploids versus diploids and how the described fitness relationships could
      contribute to the outstanding role of sex chromosomes as hotspots of sexual
      antagonism and genes involved in speciation.

PMID- 29328539
TI  - Early detection of myocardial involvement by T1 mapping of cardiac MRI in
      idiopathic inflammatory myopathy.
AB  - BACKGROUND: Polymyositis (PM) and dermatomyositis (DM) are common types of
      idiopathic inflammatory myopathy (IIM), wherein patients are prone to adverse
      cardiovascular events. PURPOSE: To explore the value of cardiac magnetic
      resonance imaging (MRI) for detecting cardiac involvement in PM/DM patients using
      a T1 mapping technique. STUDY TYPE: Prospective observational study. POPULATION:
      In all, 25 PM/DM patients free of cardiovascular symptoms and preserved
      ventricular systolic function and 25 healthy volunteers matched for age and sex
      served as controls. FIELD STRENGTH/SEQUENCE: Cardiac MRI at 3T, including steady
      state free precession (SSFP) cine imaging, late gadolinium enhancement (LGE), and
      T1 mapping with modified Look-Locker inversion recovery (MOLLI). ASSESSMENT:
      Myocardial native T1 and extracellular volume (ECV) of the left ventricle as well
      as the correlations with disease activity were analyzed. STATISTICAL TESTS:
      Independent sample's t-test, Fisher's exact test, or chi-square test, Pearson's
      correlation (r) were applied. P <= 0.05 was considered significant. RESULTS: Left
      ventricular end-diastolic/end-systolic volume index (P = 0.643, P = 0.325,
      respectively), mass index (P = 0.719), and ejection fraction (P = 0.144) were not
      significantly different between PM/DM patients and controls. LGE was found in 19%
      of PM/DM patients and none of the control subjects. PM/DM patients showed
      significantly higher native T1 values (1263.7 +/- 84.0 msec vs. 1200.6 +/- 43.0
      msec, P = 0.002) and expanded extracellular volume (ECV) (32.6 +/- 3.7% vs. 26.7
      +/- 2.3%, P < 0.001) compared with control subjects. ECV values in PM/DM patients
      had a high proportion (60%) over the 95% percentile of normal controls.
      Meanwhile, there was a significant correlation between native T1 (r = 0.710, P =
      0.0001) or ECV (r = 0.508, P = 0.01) and N-terminal prohormone of brain
      natriuretic peptide (NT-proBNP). DATA CONCLUSION: T1 mapping of cardiac MRI is
      valuable to detect subclinical myocardial involvement in PM/DM patients, and both
      myocardial native T1 and ECV could serve as early imaging markers for myocardial
      impairment in PM/DM. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 3 J. MAGN.
      RESON. IMAGING 2018;48:415-422.

PMID- 29328540
TI  - Case of late-onset, relapsing surgical site infection related to a venous coupler
      placed during free flap reconstruction for major head and neck cancer.
AB  - BACKGROUND: Venous coupling devices are widely used during reconstructive surgery
      involving microvascular anastomosis but have not served as foreign bodies in head
      and neck surgical site infections. METHODS: We conducted a case report. RESULTS:
      A patient underwent resection and free flap reconstruction for recurrent tongue
      squamous cell carcinoma. She developed a neck abscess due to Streptococcus
      intermedius 7 weeks postoperatively, days after starting chemoradiotherapy. The
      surgical site infection healed with drainage and antibiotics. Two surgical site
      infection relapses due to S. intermedius occurred 3 and 8 weeks after completing
      radiation, the second relapse after a prolonged course of i.v. antibiotics.
      Surgical exploration revealed a venous coupler within granulation tissue. The
      device was removed and no further surgical site infection relapses occurred.
      CONCLUSION: To the best of our knowledge, this is the first report of a delayed
      onset head and neck surgical site infection in which a venous coupler served as a
      foreign body. An infected foreign body should be suspected in relapsing surgical
      site infections due to a single organism.

PMID- 29328541
TI  - GM-CSF ameliorates microvascular barrier integrity via pericyte-derived Ang-1 in
      wound healing.
AB  - Skin wound healing involves complex coordinated interactions of cells, tissues,
      and mediators. Maintaining microvascular barrier integrity is one of the key
      events for endothelial homeostasis during wound healing. Vasodilation is observed
      after vasoconstriction, which causes blood vessels to become porous, facilitates
      leukocyte infiltration and aids angiogenesis at the wound-area, postinjury.
      Eventually, vessel integrity has to be reestablished for vascular maturation.
      Numerous studies have found that granulocyte macrophage colony-stimulating factor
      (GM-CSF) accelerates wound healing by inducing recruitment of repair cells into
      the injury area and releases of cytokines. However, whether GM-CSF is involving
      in the maintaining of microvascular barrier integrity and the underlying
      mechanism remain still unclear. Aim of this study was to investigate the effects
      of GM-CSF on modulation of microvascular permeability in wound healing and
      underlying mechanisms. Wound closure and microvascular leakage was investigated
      using a full-thickness skin wound mouse model after GM-CSF intervention. The
      endothelial permeability was measured by Evans blue assay in vivo and in vitro
      endothelium/pericyte co-culture system using a FITC-Dextran permeability assay.
      To identify the source of angiopoietin-1 (Ang-1), double staining is used in vivo
      and ELISA and qPCR are used in vitro. To determine the specific effect of Ang-1
      on GM-CSF maintaining microvascular stabilization, Ang-1 siRNA was applied to
      inhibit Ang-1 production in vivo and in vitro. Wound closure was significantly
      accelerated and microvascular leakage was ameliorated after GM-CSF treatment in
      mouse wound sites. GM-CSF decreased endothelial permeability through tightening
      endothelial junctions and increased Ang-1 protein level that was derived by
      perictye. Furthermore, applications of siRNAAng-1 inhibited GM-CSF mediated
      protection of microvascular barrier integrity both in vivo and in vitro. Our data
      indicate that GM-CSF ameliorates microvascular barrier integrity via pericyte
      derived Ang-1 during wound healing.

PMID- 29328542
TI  - Towards the Detection of Explosive Taggants: Microwave and Millimetre-Wave Gas
      Phase Spectroscopies of 3-Nitrotoluene.
AB  - The monitoring of gas-phase mononitrotoluenes is crucial for defence, civil
      security and environmental interests because they are used as taggant for TNT
      detection and in the manufacturing of industrial compounds such as dyestuffs. In
      this study, we have succeeded to measure and analyse at high-resolution a room
      temperature rotationally resolved millimetre-wave spectrum of meta-nitrotoluene
      (3-NT). Experimental and theoretical difficulties have been overcome, in
      particular, those related to the low vapour pressure of 3-NT and to the presence
      of a CH3 internal rotation in an almost free rotation regime (V3 =6.7659(24) cm-1
      ). Rotational spectra have been recorded in the microwave and millimetre-wave
      ranges using a supersonic jet Fourier Transform microwave spectrometer (Trot <10
      K) and a millimetre-wave frequency multiplication chain (T=293 K), respectively.
      Spectral analysis of pure rotation lines in the vibrational ground state and in
      the first torsional excited state supported by quantum chemistry calculations
      permits the rotational energy of the molecule, the hyperfine structure due to the
      14 N nucleus, and the internal rotation of the methyl group to be characterised.
      A line list is provided for future in situ detection.

PMID- 29328543
TI  - The Sarda Sheep Host Fecal Proteome.
AB  - The first characterization of the sheep fecal microbiota was recently reported,
      as obtained by using a multi meta-omic approach. Here, the mass spectra generated
      by single-run LC/high-resolution MS in the context of that study were reanalyzed
      using a host-specific database, in order to gain insights for the first time into
      the host fecal proteome of healthy Sarda sheep. On the whole, 5349 non-redundant
      tryptic peptide sequences were identified, belonging to 1046 different proteins.
      The "core" fecal proteome (common to all animals) comprised 431 proteins, mainly
      related to biological processes as immune response and proteolysis. Proteins
      involved in the immune/inflammatory response and peptidases were specifically
      investigated. This dataset provides novel insights into the repertoire of
      proteins secreted in the sheep intestinal lumen, and constitutes the basis for
      future shotgun and targeted proteomics studies aimed at monitoring changes in the
      sheep fecal proteome in response to production variables, infectious/inflammatory
      states, and variations in the gut microbiota. Data are available via
      ProteomeXchange with identifier PXD006145.

PMID- 29328544
TI  - Association between hedonic hunger and glycemic control in non-obese and obese
      patients with type 2 diabetes.
AB  - AIMS/INTRODUCTION: Higher hedonic hunger has been observed in obese individuals
      compared with those without obesity, but little is known about its association
      with glycemic management. We aimed to examine the association between hedonic
      hunger and glycemic control in non-obese and obese patients with type 2 diabetes.
      MATERIALS AND METHODS: Between April and November 2016, a total of 211 type 2
      diabetes patients who underwent comprehensive diabetes assessments at a
      university-affiliated hospital were recruited into two groups according to body
      mass index: non-obese (body mass index 18.5-24.9 kg/m2 ) and obese (body mass
      index >=30 kg/m2 ) groups. All participants completed the Chinese version of the
      Power of Food Scale (PFS) for assessment of hedonic hunger. Good glycemic control
      was defined as glycated hemoglobin <7.0%. RESULTS: Compared with the non-obese
      group, the obese group showed higher PFS aggregated and subscale 'food available'
      scores (both P < 0.05). After adjustment for age, sex, disease duration of
      diabetes and insulin use, there were positive associations of glycated hemoglobin
      with PFS aggregated, subscale 'food available' and 'food present' scores in the
      obese group (all P for trend <0.05). The PFS aggregated score was negatively
      associated with good glycemic control in obese type 2 diabetes patients after
      adjustment using logistic regression analysis (adjusted odds ratio 0.42, 95%
      confidence interval 0.20-0.91, P = 0.027). By contrast, such associations were
      not observed in non-obese type 2 diabetes patients. CONCLUSIONS: Hedonic hunger
      had an independent and inverse association with good glycemic control in obese
      Chinese patients with type 2 diabetes, but not in their counterparts without
      obesity.

PMID- 29328546
TI  - Pleomorphic lipoma.

PMID- 29328545
TI  - Computer Simulation Elucidates Yeast Flocculation and Sedimentation for Efficient
      Industrial Fermentation.
AB  - Flocculation plays an important role in the immobilized fermentation of biofuels
      and biochemicals. It is essential to understand the flocculation phenomenon at
      physical and molecular scale; however, flocs cannot be studied directly due to
      fragile nature. Hence, the present study is focused on the morphological
      specificities of yeast flocs formation and sedimentation via the computer
      simulation by a single floc growth model, based on Diffusion-Limited Aggregation
      (DLA) model. The impact of shear force, adsorption, and cell propagation on
      porosity and floc size is systematically illustrated. Strong shear force and weak
      adsorption reduced floc size but have little impact on porosity. Besides, cell
      propagation concreted the compactness of flocs enabling them to gain a larger
      size. Later, a multiple flocs growth model is developed to explain sedimentation
      at various initial floc sizes. Both models exhibited qualitative agreements with
      available experimental data. By regulating the operation constraints during
      fermentation, the present study will lead to finding optimal conditions to
      control the floc size distribution for efficient fermentation and harvesting.

PMID- 29328547
TI  - Blow flies as urban wildlife sensors.
AB  - Wildlife detection in urban areas is very challenging. Conventional monitoring
      techniques such as direct observation are faced with the limitation that urban
      wildlife is extremely elusive. It was recently shown that invertebrate-derived
      DNA (iDNA) can be used to assess wildlife diversity in tropical rainforests.
      Flies, which are ubiquitous and very abundant in most cities, may also be used to
      detect wildlife in urban areas. In urban ecosystems, however, overwhelming
      quantities of domestic mammal DNA could completely mask the presence of wild
      mammal DNA. To test whether urban wild mammals can be detected using fly iDNA, we
      performed DNA metabarcoding of pools of flies captured in Berlin, Germany, using
      three combinations of blocking primers. Our results show that domestic animal
      sequences are, as expected, very dominant in urban environments. Nevertheless,
      wild mammal sequences can often be retrieved, although they usually only
      represent a minor fraction of the sequence reads. Fly iDNA metabarcoding is
      therefore a viable approach for quick scans of urban wildlife diversity.
      Interestingly, our study also shows that blocking primers can interact with each
      other in ways that affect the outcome of metabarcoding. We conclude that the use
      of complex combinations of blocking primers, although potentially powerful,
      should be carefully planned when designing experiments.

PMID- 29328549
TI  - Synthesis of polydopamine-functionalized magnetic graphene and carbon nanotubes
      hybrid nanocomposites as an adsorbent for the fast determination of 16 priority
      polycyclic aromatic hydrocarbons in aqueous samples.
AB  - A novel adsorbent made of polydopamine-functionalized magnetic graphene and
      carbon nanotubes hybrid nanocomposite was synthesized and applied to determine 16
      priority polycyclic aromatic hydrocarbons by magnetic solid phase extraction in
      water samples. FTIR spectroscopy, transmission electron microscopy, scanning
      electron microscopy, and Raman spectroscopy consistently indicate that the
      synthesized adsorbents are made of core-shell nanoparticles well dispersed on the
      surface of graphene and carbon nanotubes. The major factors affecting the
      extraction efficiency, including the pH value of samples, the amount of
      adsorbent, adsorption time and desorption time, type and volume of desorption
      solvent, were systematically optimized. Under the optimum extraction conditions,
      a linear response was obtained for polycyclic aromatic hydrocarbons between
      concentrations of 10 and 500 ng/L with the correlation coefficients ranging from
      0.9958 to 0.9989, and the limits of detection (S/N = 3) were between 0.1 and 3.0
      ng/L. Satisfactory results were also obtained when applying these magnetic
      graphene/carbon nanotubes/polydopamine hybrid nanocomposites to detect polycyclic
      aromatic hydrocarbons in several environmental aqueous samples.

PMID- 29328548
TI  - Copper-Catalyzed Oxidative Reaction of beta-Keto Sulfones with Alcohols via C-S
      Bond Cleavage: Reaction Development and Mechanism Study.
AB  - A Cu-catalyzed cascade oxidative radical process of beta-keto sulfones with
      alcohols has been achieved by using oxygen as an oxidant. In this reaction, beta
      keto sulfones were converted into sulfinate esters under the oxidative conditions
      via cleavage of C-S bond. Experimental and computational studies demonstrate that
      a new pathway is involved in this reaction, which proceeds through the formation
      of the key four-coordinated CuII intermediate, O-O bond homolysis induced C-S
      bond cleavage and Cu-catalyzed esterification to form the final products. This
      reaction provides a new strategy to sulfonate esters and enriches the research
      content of C-S bond cleavage and transformations.

PMID- 29328550
TI  - Synthesis of Hollow Mesoporous TiO2 Microspheres with Single and Double Au
      Nanoparticle Layers for Enhanced Visible-Light Photocatalysis.
AB  - A facile method was used to prepare hollow mesoporous TiO2 and Au@TiO2 spheres
      using polystyrene (PS) templates. Au nanoparticles (NPs) were simultaneously
      synthesized and attached on the surface of PS spheres by reducing AuCl4- ions
      using sodium citrate which resulted in the uniform deposition of Au NPs. The
      outer coating of titania via sol-gel produced PS@Au@TiO2 core-shell spheres.
      Removing the templates from these core-shell spheres through calcination produced
      hollow mesoporous and crystalline Au@TiO2 spheres with Au NPs inside the TiO2
      shell in a single step. Anatase spheres with double Au NPs layers, one inside and
      another outside of TiO2 shell, were also prepared. Different characterization
      techniques indicated the hollow mesoporous and crystalline morphology of the
      prepared spheres with Au NPs. Hollow anatase spheres with Au NPs indicated
      enhanced harvesting of visible light and therefore demonstrated efficient
      catalytic activity toward the degradation of organic dyes under the irradiation
      of visible light as compared to bare TiO2 spheres.

PMID- 29328553
TI  - Skin-colored papules on the elbows with a granuloma-annulare-like histological
      pattern.

PMID- 29328552
TI  - Changes in Chromosome Counts and Patterns in CHO Cell Lines upon Generation of
      Recombinant Cell Lines and Subcloning.
AB  - Chinese hamster ovary (CHO) cells are the number one production system for
      therapeutic proteins. A pre-requirement for their use in industrial production of
      biopharmaceuticals is to be clonal, thus originating from a single cell in order
      to be phenotypically and genomically identical. In the present study it was
      evaluated whether standard procedures, such as the generation of a recombinant
      cell line in combination with selection for a specific and stable phenotype
      (expression of the recombinant product) or subcloning have any impact on
      karyotype stability or homogeneity in CHO cells. Analyses used were the
      distribution of chromosome counts per cell as well as chromosome painting to
      identify specific karyotype patterns within a population. Results indicate that
      subclones both of the host and the recombinant cell line are of comparable
      heterogeneity and (in)stability as the original pool. In contrast, the rigorous
      selection for a stably expressing phenotype generated cell lines with fewer
      variation and more stable karyotypes, both at the level of the sorted pool and
      derivative subclones. We conclude that the process of subcloning itself does not
      contribute to an improved karyotypic homogeneity of a population, while the
      selection for a specific cell property inherently can provide evolutionary
      pressure that may lead to improved chromosomal stability as well as to a more
      homogenous population.

PMID- 29328554
TI  - Cross-Mapping of Nursing Care Terms Recorded in Italian Hospitals into the
      Standardized NNN Terminology.
AB  - PURPOSE: To evaluate if nursing diagnoses, interventions, and outcomes, as
      recorded by nurses in Italian hospitals, were semantically equivalent to the
      NANDA-I, NIC, and NOC (NNN) terminology. METHODS: A cross-mapping study using a
      multicenter design. Terms indicating nursing diagnoses, interventions, and
      outcomes were collected using the D-Catch instrument. Cross-mapping of these
      terms with NNN terminology was performed. FINDINGS: A sample of 137 nursing
      documentations was included. Over 80% of nursing diagnostic terms, interventions,
      and outcomes were cross-mapped into NNN terminology. CONCLUSIONS: The study
      showed that most of the natural terms used by nurses were semantically equivalent
      to the standardized terms of NNN terminology. IMPLICATIONS FOR NURSING PRACTICE:
      In Italy, the use of NNN terminology is recommended; however, further development
      of this terminology is needed.

PMID- 29328551
TI  - Failure of monotherapy in clinical practice in patients with type 2 diabetes: The
      Korean National Diabetes Program.
AB  - AIMS/INTRODUCTION: We investigated the failure of monotherapy in patients with
      type 2 diabetes mellitus in real practice settings. MATERIALS AND METHODS: The
      Korean National Diabetes Program was a prospective, multicenter observational
      cohort study of type 2 diabetes mellitus patients in Korea. Of the 3,950 patients
      enrolled in the study, we studied 998 who were continuously maintained on
      monotherapy for at least 90 days at six participating centers. To balance the
      baseline characteristics of patients in each group, we used propensity matching
      at a 1:1 ratio (metformin vs sulfonylureas) and 4:1 ratio (metformin vs
      meglitinides and metformin vs alpha-glucosidase inhibitors [aGIs]). The hazard
      ratios (HRs) of treatments (compared with metformin) were determined by Cox's
      proportional hazards regression modeling. RESULTS: The median follow-up time was
      56 months, and monotherapy failed in 45% of all patients. The annual incidences
      of failure were 15.6%, 21.3%, 27% and 9.6% in the metformin, sulfonylurea,
      meglitinide and aGI groups. Compared with metformin, sulfonylureas and
      meglitinides were associated with higher risks of monotherapy failure (HR 1.39,
      95% confidence interval [CI] 1.08-1.80; HR 1.92, 95% CI 1.13-3.27), and aGIs with
      risks similar to that of metformin (HR 0.80, 95% CI 0.44-1.45). When analyzed by
      failure type, sulfonylureas, meglitinides and aGIs were associated with a higher
      risk of a switch to other agents (HR 4.43, 95% CI 2.14-9.17; HR 18.80, 95% CI
      6.21-56.93; HR 4.25, 95% CI 1.49-12.13), and aGIs with a lower risk of
      prescription of add-on second agents (HR 0.16, 95% CI 0.04-0.64). CONCLUSIONS:
      Metformin was associated with a lower failure risk than were sulfonylureas and
      meglitinides, but a comparable aGI failure rate.

PMID- 29328555
TI  - Syntheses and Properties of meso-Substituted Porphyrin Mesogens with Triazole
      Linkages and Peripheral Alkyl Chains.
AB  - Discotic mesogens P/n-M (n=12, 16, 18, M=2 H, Zn and Cu) bearing a porphyrin
      core, triazole linkages and peripheral 3,4,5-trialkoxybenzyl units have been
      synthesized by a click-chemistry approach. The thermal behavior, photophysical
      properties and morphologies of these compounds were investigated by polarized
      optical microscopy (POM), differential scanning calorimetry (DSC), XRD, UV and
      PL, SEM and TEM. These compounds can self-assemble into hexagonal columnar phases
      in their pure states and form organogels in 1,4-dioxane with unusually flower
      like sphere morphology. The supramolecular complexes of P/18-Zn with C70 or 4,7
      di-4-pydriyl-2,1,3-benzothadiazole can display hexagonal columnar phases too.
      Additionally, zinc porphyrin compounds P/n-Zn show binding selectivity to Cu2+
      among a series of cations in THF/H2 O.

PMID- 29328557
TI  - Clipping cancer with CRISPR: The precise gene-editing tool is showing promise in
      early cancer studies, although obstacles remain.

PMID- 29328558
TI  - Endovascular treatment of the subclavian artery aneurysm in high-risk patient - a
      single-center experience.
AB  - We present our first experience with endovascular treatment of 6 subclavian
      artery aneurysms (SAA) occurring in five male and one female patient. All
      patients, in our studies, according to ASA classification were high risk for open
      repair of SAA. The etiology of the all aneurysms was atherosclerosis degeneration
      of the artery. Two aneurysms were of intrathoracic location, then the other were
      extrathoracic. Symptoms related to subclavian artery aneurysms were present in
      two patients, compression and chest pain in one, and hemorrhage shock in second,
      while the remaining patients were asymptomatic. We preferred the Viabhan
      endoprosthesis for endovascular repair in 5 cases. In one patient with ruptured
      of subclavian artery aneurysm who was high-risk for open repair we made combined
      endovascular procedure. First at all, we covered the origin of left subclavian
      artery with thoracic stent graft and after that we put two coils in proximal part
      of subclavian artery. There was no operative mortality, and the early patency
      rate was 100%. The follow-up period was from 3 months to 3 years. During this
      period, one patient died of heart failure and one patient required endovascular
      reoperation due to endoleak type I. Endovascular treatment is recommended for all
      patients with subclavian artery aneurysm whenever this is possible due to
      anatomical reasons especially in high-risk patient with intrathoracic
      localization of aneurysm, to prevent potential complications.

PMID- 29328559
TI  - Detection of influenza viruses by reverse transcription polymerase chain
      reaction: WHO external quality assessment programme summary analysis, 2017.

PMID- 29328556
TI  - Coronary artery disease in decompensated patients undergoing liver
      transplantation evaluation.
AB  - Coronary artery disease (CAD) is an important contributor to morbidity and
      mortality in patients undergoing liver transplantation (LT). However, the current
      literature is limited by sampling bias and nondefinitive assessment of CAD. The
      current study examines the prevalence of CAD via per protocol coronary
      angiography and its relationship to etiology of liver disease in patients
      undergoing liver transplantation evaluation (LTE). Data on 228 patients were
      prospectively collected who had coronary angiography as part of LTE between 2011
      and 2014. Coronary angiography was done in all patients age >=50 years or with
      CAD risk factors. CAD was defined as any coronary artery stenosis, whereas
      stenosis >= 70% in distribution of 1 or 3 major coronary arteries was considered
      as single- or triple-vessel disease. CAD was detected in 36.8% of patients, with
      the highest prevalence among nonalcoholic steatohepatitis (NASH) patients with
      cirrhosis (52.8%). Prevalence of single-vessel disease was higher among patients
      with NASH compared with hepatitis C virus (HCV) and alcoholic cirrhosis (15.1%
      versus 4.6% versus 6.6%; P = 0.02). Similarly, patients with NASH were more
      likely to have triple-vessel disease when compared with HCV and alcoholic
      cirrhosis (9.4% versus 0.9% versus 0%; P = 0.001). While adjusting for
      traditional risk factors for CAD, only NASH as etiology of liver disease remained
      significantly associated with CAD. Complications from diagnostic coronary
      angiography or percutaneous coronary intervention were low (2.6%). In conclusion,
      patients undergoing LTE have a high prevalence of CAD, which varies widely
      depending on etiology of liver cirrhosis. The procedural complications from
      coronary angiography are low. Liver Transplantation 24 333-342 2018 AASLD.

PMID- 29328560
TI  - Re-evaluating disability assessment in war veterans with posttraumatic stress
      disorder.
AB  - Background/Aim: Sametimes war veterans may resort to such strategies as preducing
      exaggerated symptoms and malingerating in order to obtain material compensation
      rights. The aim of this study was to assess the accuracy of the diagnosis of
      posttraumatic stress disorder (PTSD) on the basis of which war veterans were
      entitled to a financial compensation due to their disability. Methods: The
      diagnoses of 259 war veterans were re-evaluated. Veterans were previously
      diagnosed by a psychiatrist on local level, while regional state medical
      commission determined the degree of disability and the right to a financial
      compensation. A team of experts, consisting of psychiatrists with research
      experience in the field of traumatic stress and who were trained to use a
      structured interview for PTSD, conducted the evaluation of medical data from
      veterans' military records. The diagnostic process was conducted using the
      standardized diagnostic interview (Clinician-Administered PTSD Scale - CAPS),
      after which the diagnosis was reaffirmed or reviewed. This influenced disability
      status and consequential financial compensation. Results: There was a remarkable
      difference between the first diagnostic assessment of PTSD, conducted by the
      psychiatrists on local level, and the second evaluation conducted by the team of
      experts. In more than half of 259 veterans (52.1%) diagnosed with PTSD in the
      first assessment the diagnosis was not confirmed. The diagnosis was confirmed in
      31.7% of veterans. Those veterans who were diagnosed with lifetime PTSD (7.3%)
      should also be treated as accuratelly diagnosed. This means that a total of 39%
      of the diagnoses were accurate. The rest (8.9%) were diagnosed with other
      diagnoses, but not PTSD, as was the case in the initial assessment. Conclusion:
      The possibility for war veterans to obtain the right to disability and financial
      compensation due to a diagnosis of PTSD might interfere with the proper
      diagnostic assessment and thus the treatment outcome. During the procedures for
      the obtention of these rights, exaggeration or simulation of symptoms are common.
      The quality of the diagnostic assessment of PTSD can be improved by applying
      evidence based standardized procedures.

PMID- 29328561
TI  - Lung ultrasound for severe acute dyspnea evaluation in critical care patients.

PMID- 29328562
TI  - Hereditary hemorrhagic telangiectasia with bilateral pulmonary vascular
      malformations: A case report.
AB  - Introduction: Hereditary hemorrhagic telangiectasia (HHT) also known as Osler
      Weber-Rendu syndrome is an autosomal dominant disease that occurs due to vascular
      dysplasia associated with the disorder in the signaling pathway of transforming
      growth factor beta (TGF-beta). The clinical consequence is a disorder of blood
      vessels in multiple organ systems with the existence of telangiectasia which
      causes dilation of capillaries and veins, are present from birth and are
      localized on the skin and mucosa of the mouth, respiratory, gastrointestinal and
      urinary tract. They can make a rupture with consequent serious bleeding that can
      end up with fatal outcome. Since there is a disruption of blood vessels of more
      than one organic system, the diagnosis is very complex and requires a
      multidisciplinary approach. Case report: We reported a 40-year-old female patient
      with a long-time evolution of problems, who was diagnosed and treated at the
      Clinic for Lung Diseases of the Military Medical Academy in Belgrade, Serbia,
      because of bilaterally pulmonary arteriovenous malformations associated with HHT.
      Embolization was performed in two acts, followed with normalization of clinical,
      radiological and functional findings with the cessation of hemoptysis, effort
      intolerance with a significant improvement of the quality of life. Conclusion:
      HHT is a rare dominant inherited multisystem disease that requires
      multidisciplinary approach to diagnosis and treatment. Embolization is the method
      of choice in the treatment of arteriovenous malformations with minor adverse
      effects and very satisfying therapeutic effect.

PMID- 29328563
TI  - Coexisting diseases modifying each other's presentation - lack of growth failure
      in Turner syndrome due to the associated pituitary gigantism.
AB  - Introduction: Turner syndrome presents with one of the most frequent chromosomal
      aberrations in female, typically presented with growth retardation, ovarian
      insufficiency, facial dysmorphism, and numerous other somatic stigmata. Gigantism
      is an extremely rare condition resulting from an excessive growth hormone (GH)
      secretion that occurs during childhood before the fusion of epiphyseal growth
      plates. The major clinical feature of gigantism is growth acceleration, although
      these patients also suffer from hypogonadism and soft tissue hypertrophy. Case
      report: We presented a girl with mosaic Turner syndrome, delayed puberty and
      normal linear growth for the sex and age, due to the simultaneous GH
      hypersecretion by pituitary tumor. In the presented case all the typical
      phenotypic stigmata related to Turner syndrome were missing. Due to excessive
      pituitary GH secretion during the period while the epiphyseal growth plates of
      the long bones are still open, characteristic stagnation in longitudinal growth
      has not been demonstrated. The patient presented with delayed puberty and primary
      amenorrhea along with a sudden appearance of clinical signs of
      hypersomatotropinism, which were the reasons for seeking medical help at the age
      of 16. Conclusion: Physical examination of children presenting with delayed
      puberty but without growth arrest must include an overall hormonal and genetic
      testing even in the cases when typical clinical presentations of genetic disorder
      are absent. To the best of our knowledge, this is the first reported case of
      simultaneous presence of Turner syndrome and gigantism in the literature.

PMID- 29328564
TI  - Pemphigus herpetiformis - a case report of a rare form of pemphigus and review of
      the literature.
AB  - Introduction: Pemphigus herpetiformis is the rare variant of pemphigus with
      characteristic clinical features, histopathological findings different from the
      convectional pemphigus, and immunological findings consistent with pemphigus.
      Case report: We presented a 65-year-old woman with initial pruritus followed by
      pruritic urticarial papules and plaques, some with annular rings of tense
      vesicles on the periphery, on the trunk and extremities, with no mucous lesions.
      Histopathological examination demonstrated spongiosis and intraepidermal vesicles
      in the mid or subcorneal epidermis in some biopsy specimen, with neutrophil and
      eosinophil infiltrate. Direct immunoflorescent microscopy revealed intercellular
      IgG deposition, most prominent in the upper layers of epidermis. Indirect
      immunoflorescent microscopy showed intercellular binding of IgG autoantibodies in
      the patient's sera. Initially the patient was threated with systemic
      corticosteroids and azathioprine, but dapson provided complete clinical
      remission. Conclusion: This entity was established 40 years ago, and around 100
      patients have been reported worldwide. It is important to be aware of this
      particular form of pemphigus because clinical presentation, course of the disease
      and therapeutic approach are different from conventional forms of pemphigus.

PMID- 29328565
TI  - Urrets-Zavalia syndrome after deep anterior lamellar keratoplasty
AB  - Introduction: Urrets-Zavalia syndrome is an uncommon complication of the deep
      anterior lamellar keratoplasty in keratoconus. The manifestations of this
      syndrome are an irreversible mydriasis, iris atrophy and secondary glaucoma. Case
      report: Deep anterior lamellar keratoplasty was done for keratoconus with a
      presumably healed corneal hydrops in a 21-year-old Caucasian man. The graft
      remained clear, but the surgery was complicated by a fixed, dilated pupil,
      patches of iris atrophy, ectropium of the iris pigment layer and glaukomflecken
      in the lens. Conclusion: Although safer than penetrating keratoplasty, the deep
      anterior lamellar by not trying to secure an unhealed Descemet's membrane with
      air. Instead, a new Descemet's membrane transplanted within a penetrating graft
      is a safer choice.

PMID- 29328566
TI  - Contribution of Dr. Laza Popovic to the development of Serbian and Yugoslav Sokol
      movement.

PMID- 29328567
TI  - Neglected zoonosis: The prevalence of Salmonella spp. in pet reptiles in Serbia.

PMID- 29328568
TI  - The attitudes of medical students towards rare diseases: A cross-sectional study.
AB  - Background/Aim: Rare diseases are chronic, degenerative and may lead to permanent
      disability. We aimed to assess knowledge and attitudes of the 3rd and 6th year
      medical students towards the treatment of rare diseases in Serbia. Methods. In
      this cross-sectional study, two samples of students were questioned for a survey:
      350/446 (78.48%) students of the 3rd year, and 242/517 (46.81%) students of the
      6th year. Methods: In this cross-sectional study, two samples of students were
      questioned for a survey: 350/446 (78.48%) students of the 3rd year, and 242/517
      (46.81%) students of the 6th year. Results: Sixth year students estimated that
      they were more informed on the issue analyzed than the 3rd year students (median
      value of 4 and 3, interquartile range of 3-5, and 1-4, respectively; p < 0.05).
      However, a significant percentage of participants estimated incorrectly the
      prevalence of rare diseases according to the European Union standards (3rd year -
      42.68%, 6th year - 49.55%). Core curriculum subjects were the main source of
      information on rare diseases (3rd year - 63.14%; 6th year - 92.14%). Our
      participants agreed that the most important problems are the following: high drug
      prices, difficult access to drugs and lack of public information. Students found,
      without any differences, that community access to effective drugs for rare
      disease should be improved (median value - 10, interquartile range 8-10 in both
      groups, p < 0.05). In order to improve pharmacotherapy of rare diseases in
      Serbia, the participants suggested establishment of a National Plan for Rare
      Diseases, approval of more appropriate drugs, simplified access to appropriate
      medicines, and more rapid diagnostics. Conclusion: It is necessary to improve the
      knowledge and attitudes of medical students towards pharmacotherapy of rare
      diseases. [Projekat Ministarstva nauke Republike Srbije, br. 175023]

PMID- 29328582
TI  - Adverse event reporting in Slovenia - the influence of safety culture,
      supervisors and communication.
AB  - Background/Aim: The provision of safe healthcare is considered a priority in
      European Union (EU) member states. Along with other preventative measures in
      healthcare, the EU also strives to eliminate the "causes of harm to human
      health". The aim of this survey was to determine whether safety culture,
      supervisors and communication between co-workers influence the number of adverse
      event reports submitted to the heads of clinical departments and to the
      management of an institution. Methods: This survey is based on cross-sectional
      analysis. It was carried out in the largest Slovenian university hospital. We
      received 235 completed questionnaires. Respondents included professionals in the
      fields of nursingcare, physiotherapy, occupational therapy and radiological
      technology. Results: Safety culture influences the number of adverse event
      reports submitted to the head of a clinical department from the organizational
      point of view. Supervisors and communication between co-workers do not influence
      the number of adverse event reports. Conclusion: It can be concluded that neither
      supervisors nor the level of communication between co-workers influence the
      frequency of adverse event reporting, while safety culture does influence it from
      an organizational point of view. The presumed factors only partly influence the
      number of submitted adverse event reports, thus other causes of under-reporting
      must be sought elsewhere.

PMID- 29328583
TI  - Analysis of reconstructive methods in surgical treatment of nasal skin defects.
AB  - Background/Aim: Surgeons often face with the problem when selecting a
      reconstructive method for nasal skin defects. The aim of this study was to
      determine functional and aesthetic character-istics of different reconstructive
      methods used for skin defects in different regions of the nose. Methods: The
      study involved 44 patients with basocellular carcinoma in nasal area. The nasal
      skin was divided into four subunits: the tip, the alar lobules, the side-walls
      and the dorsum. The average skin defect size was 10 mm in diameter. Local flaps
      and full thickness skin grafts were used in the study. We analyzed the functional
      and esthetic results of dif-ferent reconstructive methods used for nasal defects
      in different regions of the nose 12 months after the surgery. Results: The study
      shows that different reconstructive methods produce dif-ferent functional and
      esthetic results in the same nasal subunits and that the same reconstructive
      method produces different re-sults in different nasal subunits. Conclusions:
      Estimation the postoperative functional and esthetic characteristics of different
      reconstructive methods is one of the basic preconditions of suc-cessful
      reconstruction.

PMID- 29328596
TI  - Influence of dental filling material type on the concentration of interleukin 9
      in the samples of gingival crevicular fluid.
AB  - Background/Aim: Several cytokines and lymphokines (IL1beta, ENA78, IL6, TNFalpha,
      IL8 and S100A8) are expressed during dental pulp inflammation. Analysis of
      gingival crevicu-lar fluid (GCF) offers a non-invasive means of studying gen-eral
      host response in oral cavity. Although GCF levels of various mediators could
      reflect the state of inflammation both in dental pulp and gingiva adjacent to a
      tooth, GCF samples of those without significant gingivitis could be inter-preted
      as reflection of pulpal process. The aim of this study was to investigate IL9 GCF
      values in patients with dental car-ies and to assess possible influence of
      various dental fillings materials on local IL9 production. Methods: The study
      group included 90 patients, aged 18-70, with inclusion and exclusion criteria in
      the prospective clinical study. Of the 6 types of material used for the
      restoration of prepared cavities, 3 were intended for temporary and 3 for
      definitive restora-tion. According to dental fillings weight, all the
      participants were divided into 3 groups: those with fillings lighter than 0.50 g,
      those with 0.50-1.00 g, and those with fillings heavier than 1.00 g. Samples were
      taken from gingival sulcus using the filter paper technique. Clinical parameters
      were deter-mined by bleeding index, plaque index (Silness-Lou, 0-3), gingival
      index (0-3), and gingival sulcus depth. Cytokine con-centrations were assessed
      using commercially available cy-tomix. Results: According to the weight of dental
      fillings, there was a clear decreament trend of IL9 values meaning that dental
      defects greater than 1.00 g of dental filling were associated with lower GCF IL9
      concentration. The IL9 val-ues correlated with the degree of gingival index and
      depth of gingival sulcus, being higher with more advanced gingivitis and more
      pronounced anatomical changes in the tooth edge. Different filling materials
      exerted various local IL9 responses. Zink polycarbonate cement and amalgam
      fillings induced a significant and long-lasting local IL9 decrement, while the
      use of Tetric EvoCeram and GMA-BISK significantly increased IL9 levels.
      Conclusion: The obtained results indicate that IL9 GCF could be regarded as a
      measure of odontoblasts' re-sponse to the extensity of dental caries. The type of
      material used for dental fillings could profoundly alter biological func-tion of
      gingival and pulpal cells. Also, the results obtained in this study suggest that
      some materials could even enhance wound repair by modulating macrophage
      activation.

PMID- 29328608
TI  - Work motivation and job satisfaction of health workers in urban and rural areas.
AB  - Background/Aim: Motivated and job satisfied health professionals represent a
      basis of success of modern health institutions. The aim of this study was to
      investigate whether there was a difference in work motivation and job
      satisfaction between health workers in urban and rural areas in the region of
      Central Serbia. Methods: The study included 396 health professionals from urban
      setting, and 436 from a rural area, employed in four randomly selected health
      facilities. An anonymous questionnaire was used for data gathering. Statistical
      analysis was performed using chi2, Student t-test, Spearman's correlation
      coefficient, and logistic regression analysis. Results: Urban health
      professionals were significantly more motivated and job satisfied than
      respondents from rural area. In relation to work motivation factors and job
      satisfaction of health professionals in urban and rural areas, there were no
      significant differences in working conditions and current equipment, and in terms
      of job satisfaction there were no significant differences in relation to income
      either. Conclusion: In order to increase the level of work motivation and job
      satisfaction of health workers in rural areas, apart from better income, they
      should get more assistance and support from their supervisors, and awards for
      good job performance; interpersonal relationships, promotion and advancement
      opportunities, managerial performance and cooperation at work should be improved;
      employment security should be provided, as well as more independence at work,
      with professional supervision of health workers.

PMID- 29328609
TI  - Effect of surgical drill guide and irrigans temperature on thermal bone changes
      during drilling implant sites - thermographic analysis on bovine ribs.
AB  - Background/Aim: During drilling implant sites, mechanical energy is converted
      into thermal one resulting in transient rise in temperature of surrounding bone.
      The temperature of 47 degrees C exeeding one minute impairs osseointegration,
      compromises mechanical properties of the local bone and could cause early implant
      failure. This in vitro study aimed to assess the effect of surgical drill guide
      and temperature of irrigans on thermal changes of the local bone during drilling
      implant sites, and to test the influence of irrigans temperature on the
      temperature of surgical drill guide. Methods: A total of 48 specimens obtained
      from bovine ribs were randomly allocated to four experimental conditions
      according to the 2 x 2 factorial design: drill guide (with or without) and saline
      (at 25 degrees C or 5 degrees C). Real-time infrared thermography was used as a
      method for temperature measurement. The primary outcome was bone temperature
      change during drilling implant sites measured at 3 osteotomy depths, whereas the
      second one was change in the temperature of the drill guide. Data were analyzed
      by Brunner and Langer nonparametric analysis and Wilcoxon test. Results: The
      effect of drill guide on the changes of bone temperature was significant at the
      entrance of osteotomy, whereas the effect of saline temperature was significant
      at all osteotomy levels (p < 0.001). No significant interaction was found (p >
      0.05). Guided surgery and irrigation with saline at 25 degrees C were associated
      with the highest bone temperature increase. Increase in drill guide temperature
      was significantly higher when saline at 25 degrees C was used (p < 0.001).
      Conclusion: Guided implant site preparation generates higher temperature of the
      local bone than conventional drilling, not exceeding the threshold for thermal
      bone necrosis. Although saline at room temperature provides sufficient heat
      control during drilling, cooled saline is more effective regardless the use of
      surgical drill guide.

PMID- 29328610
TI  - Major risk factors of maternal adverse outcome in women with two or more previous
      cesarean sections.
AB  - Background/Aim: Maternal morbidity is defined as any condition that is attributed
      to or aggravated by pregnancy and childbirth that has a negative impact on the
      woman's wellbeing. In recent years, a growing trend of cesarean section rates can
      be seen throughout the world. The aim of this study was to assess factors that
      might have major impact on maternal adverse outcome in women with two or more
      previous cesarean sections. Methods: This retrospective study included women with
      single term pregnancy after two or more cesarean deliveries in a 10-year period
      (2004-2013) in the University Clinic "Narodni front" in Belgrade, Serbia. Medical
      records were reviewed for clinical data for maternal intraoperative and early
      postoperative complications regarding gestational age at delivery, the number of
      previous cesarean sections and mode of surgery (elective or emergency). Results:
      A total of 551 patients were included in the study. At 37 completed weeks
      delivered 14.1%, at 38 delivered 45.2% and at 39 completed weeks 40.7% patients.
      Women younger than 35 years more often delivered after 39 completed weeks
      compared with those over 35 years (69.2% vs 30.8%, p < 0.05). The overall rate of
      maternal complications in the study group was 16.5% with no statistical
      difference by gestational age at delivery. The overall rate of maternal adverse
      outcome was significantly less in the patients with three as compared with those
      with four or more cesareans (10.4% vs 66.7%, p < 0.05). There was a statistically
      significant difference between these groups of women regarding complications:
      scar dehiscence, the presence of adhesions, blood transfusion and admission in
      intensive care unit. Elective cesarean delivery was with less maternal
      complications compared with emergency cesarean deliveries (12.9% vs 27.3%, p <
      0.05). Conclusion: Termination of pregnancy before completed 39 weeks does not
      decrease maternal morbidity. The major impact on maternal complications has the
      number of previous cesarean deliveries (>= 3), as well as emergency cesarean
      section. Patients should be informed about potential risks for maternal health
      with increasing number of cesarean deliveries, especially after the first
      cesarean section when counseling in elective repeat cesarean vs trial of labor.

PMID- 29328611
TI  - Posttraumatic stress disorder and art group therapy: Self-expression of traumatic
      inner world of war veterans.
AB  - Background/Aim: Art therapy and drawings may serve as alternative means of
      expression and release from trauma among veterans diagnosed with posttraumatic
      stress disorder (PTSD). Methods: The retrospective clinical study of drawings of
      war veterans was performed. A total of 89 war veterans met the Diagnostics and
      Statistical Manual of Mental Disorders (DSM-IV) PTSD criteria and were
      consecutively admitted to the Day Hospital during 5 years. Art group therapy as
      part of integrative treatment was performed once a week. The group was open and
      heterogeneous. Qualitative analysis of drawings content and group protocols were
      obtained. The drawings were made by free associations. War related themes were
      explored and descriptive statistics were applied. Results: The most frequent type
      of common themes of combat stress presented battle and witnessing wounded and
      killed combatants. Less frequent were themes of graves, destroyed cities and
      broken trees. The veterans preferred black and red colors with association to
      death, blood, wounds and destroyed objects. Conclusion: Drawing could provide a
      unique, complex, visual illustration of war traumatic experiences and memories of
      posttraumatic stress disorder veterans. Art group discussion might enhance war
      veterans' verbal expression due to group support in safe setting. As adjuvant
      psychotherapy, art group therapy could enrich awareness and the ability of
      clinicians to treat hard posttraumatic stress disorder symptoms related to
      uncovered war trauma.

PMID- 29328612
TI  - The impact of in-hospital nutritional status deterioration on treatment outcome
      of adult gastroenterological patients.
AB  - Background/Aim: In the current literature, data on impact of intrahospital
      changes in patients' nutritional status on the treatment outcome are limited. The
      aim of this study was to investigate the relationship between nutritional status
      deterioration and the treatment outcome among hospitalized gastroenterological
      patients. Methods: In 650 adult gastroenterological patients nutritional status
      on admission and at discharge was evaluated using the 6 nutritional status
      assessment parameters: body mass index, triceps skinfold thickness, mid-upper arm
      muscle circumference, serum albumin concentration, lymphocyte count and
      unintentional weight loss. The influence on treatment outcome was tested for the
      nutritional status on admission, nutritional status at discharge and
      intrahospital nutritional status deterioration. Results: The incidence of
      favorable outcome in the non-undernourished and undernourished patients on
      admission was in the range 93.4-97.3% and 81.2- 91.2%, respectively. The
      incidence of favorable outcome in the non-undernourished and undernourished
      patients at discharge was in the range 94-97.4% and 80.8-88.1%, respectively.
      Favorable outcomes were obtained in 95.6-98.9% of the patients without
      nutritional status deterioration and in 87.1-90.3% of the patients with
      nutritional status deterioration. Intrahospital nutritional status deterioration
      significantly influenced the outcome, no matter what assessment parameter had
      been used (p < 0.001 for all the applied parameters). Furthermore, only the
      deterioration of nutritional status was found to be an independent predictor of
      treatment outcome (multivariate analysis Forwald Wald, p L 0.001; relative risk
      (RR) = 0.104-0.350; confidence intervals (CI) = 0.037-0.186/0.297-0.657).
      Conclusion: Deterioration of nutritional status is an independent predictor of
      adverse outcome.

PMID- 29328613
TI  - The role of lung transthoracic ultrasound in clinical practice.

PMID- 29328614
TI  - Very late stent thrombosis of bare-metal coronary stent nine years after primary
      percutaneous coronary intervention.
AB  - Introduction: Stent thrombosis (ST) in clinical practice can be classified
      according to time of onset as early (0-30 days after stent implantation), which
      is further divided into acute (< 24 hours) and subacute (1-30 days), late (> 30
      days) and very late (> 12 months). Myocardial reinfaction due to very late ST in
      a patient receiving antithrombotic therapy is very rare, and potentially fatal.
      The procedure alone and related mechanical factors seem to be associated with
      acute/subacute ST. On the other hand, in-stent neoathero-sclerosis, inflammation,
      premature cessation of antiplatelet therapy, as well as stent fracture, stent
      malapposition, un-covered stent struts may play role in late/very late ST. Some
      findings implicate that the etiology of very late ST of bare-metal stent (BMS) is
      quite different from those following drug-eluting stent (DES) implantation. Case
      report: We presented a 56-year old male with acute inferoposterior ST segment
      elevation myocardial infarction (STEMI) related to very late stent thrombosis, 9
      years after BMS implantation, despite antithrombotic therapy. Thrombus aspiration
      was successfully performed followed by percutaneous coronary intervention (PCI)
      with implantation of DES into the pre-viously implanted two stents to solve the
      in-stent restenosis. Conclusion: Very late stent thrombosis, although fortu
      nately very rare, not completely understood, might cause myocardial reinfaction,
      but could be successfully treated with thrombus aspiration followed by primary
      PCI. Very late ST in the presented patient might be connected with neointimal
      plaque rupture, followed by thrombotic events.

PMID- 29328615
TI  - Ilizarov method as limb salvage in treatment of massive femoral defect after
      unsuccessful tumor arthroplasty.
AB  - Introduction: Surgical management of massive bone defects is very challenging in
      terms of estimating possibilities of saving the extremity and adequate method
      that can make it possible. Selection of methods is additionally limited in the
      presence of infection at site of defect. Case report: The female patient,
      diagnosed with Ewing sarcoma was treated by segmental bone resection and
      implantation of Kotz modular tumor endoprosthesis. After 5 years the signs of
      infection occured and persisted with low grade intensity. After falling, 12 years
      following implantation, the patient acquired periprosthetic fracture. Then
      endoprosthesis was removed, all along with surgical debridement of wound and
      application of the Ilizarov apparatus. The apparatus was applied, osteotomy of
      callus and the tibia performed with transport of bone segments, untill
      reconstruction of defect and arthrodesis of the knee was achieved. Conclusion:
      The Ilizarov apparatus offered us huge possibilities for management of massive
      bone defects with natural bone which has superior biomechanical characteristics
      comparing to the implant. The most frequent complication of this method is a
      prolonged treatment period that demands good patient selection and preparation
      and wide surgical experience.

PMID- 29328616
TI  - Cranial reconstruction with prefabricated 3D implant after a gunshot injury: A
      case report.
AB  - Introduction: Complex defects of skull bones with different etiology, still
      present the challenge in reconstructive surgery. The goldstandard for
      cranioplasty is the autologous calvarial bone graft removed during surgery which
      cannot be always applied, especially in gunshot wounds for sometimes complete
      bone destruction. Autologous reconstruction with split calvarial, rib bones or
      iliac bone graft is also possible. Materials routinely used for reconstructions
      like titanium mesh, polymethyl metacrylate (PMMA), and other have numerous
      disadvantages and limitations. Case report: We presented a patient with gunshot
      injury to the head with residual large bone defect in the frontal region, with
      involvement of the skull base, and open frontal sinus. After conservative
      treatment, six months after the injury, reconstruction of the residual bone
      defect was performed. The chosen material was computerdesigned PEEK-OPTIMA(r)
      implant, manufactured on the basis of MSCT scan. This material has not been used
      in this region so far. The postoperative and follow-up period of the next 12
      months passed without surgical complications, neurological deficit, with
      satisfactory functional and aesthetic results. Conclusion: Implanted bone
      replacement was designed and manufactured precisely according to the skull
      defect, and we found it suitable for the treatment of complex defects of the
      cranium. Early results are in favor of this cranioplasty method over standardized
      materials. Therefore, this material is expected to become a method of choice for
      reconstructive surgery of bony defects of the face and skull especially in
      complex cases.

PMID- 29328617
TI  - Sinter-Resistant and Highly Active Sub-5 nm Bimetallic Au-Cu Nanoparticle
      Catalysts Encapsulated in Silica for High-Temperature Carbon Monoxide Oxidation.
AB  - A novel gold-copper-based silica-encapsulated mixed metal oxide (MMO) core-shell
      catalyst-with sub-5 nm MMO particles-was successfully synthesized via a reverse
      micelle process. The SiO2-encapsulated MMO catalyst was reduced under hydrogen
      flow to produce an Au-Cu@SiO2 catalyst. X-ray diffraction and X-ray photoelectron
      spectroscopy characterization confirmed the presence of Au-Cu nanocomposites in
      the catalyst, while transmission electron microscopy characterization revealed
      the core-shell structure of the catalyst with the presence of sub-5 nm Au-Cu
      nanoparticle cores inside SiO2 shells. Brunauer-Emmett-Teller surface
      characterization identified that the catalyst is porous and bimodal in nature.
      The effects of promoter metal ion, catalyst pretreatment (calcination), and the
      presence of CO2 in the feed stream on carbon monoxide (CO) oxidation over the Au
      Cu@SiO2 catalyst were examined in the temperature range of 50-400  degrees C. A
      catalyst stability test was performed at 300  degrees C by conducting a CO
      oxidation reaction for 116 h on stream. The catalyst exhibited excellent efficacy
      for CO oxidation, with ~100% conversion to CO2 achieved at 400  degrees C. While
      the presence of Cu enhanced the CO conversion at low to intermediate temperatures
      (50-300  degrees C), silica encapsulation of the Au-Cu nanocomposites facilitated
      remarkable stability of the catalyst. The activity of the Au-Cu@SiO2 catalyst is
      suitable for its application in automotive after-treatment devices, especially in
      low-temperature combustion engine exhausts.

PMID- 29328618
TI  - Highly Crystalline Multicolor Carbon Nanodots for Dual-Modal Imaging-Guided
      Photothermal Therapy of Glioma.
AB  - Imaging-guided site-specific photothermal therapy (PTT) of glioma and other
      tumors in central nervous system presents a great challenge for the current
      nanomaterial design. Herein, an in situ solid-state transformation method was
      developed for the preparation of multicolor highly crystalline carbon nanodots
      (HCCDs). The synthesis yields 6-8 nm-sized HCCDs containing a highly crystalline
      carbon nanocore and a hydrophilic surface, which therefore simultaneously provide
      strong photoacoustic and photothermal performances as well as tunable
      fluorescence emission. In vitro and in vivo results demonstrate that the novel
      HCCDs have high water dispersity and good biocompatibility, but potent tumor cell
      killing upon near-infrared irradiation. As demonstrated in U87 glioma-bearing
      mice, HCCDs specifically accumulate in brain tumors and facilitate dual-modal
      imaging-guided PTT, with therapeutic antitumoral effects without any apparent
      damage to normal tissues.

PMID- 29328619
TI  - Characterization of the Polyspecific Transferase of Murine Type I Fatty Acid
      Synthase (FAS) and Implications for Polyketide Synthase (PKS) Engineering.
AB  - Fatty acid synthases (FASs) and polyketide synthases (PKSs) condense acyl
      compounds to fatty acids and polyketides, respectively. Both, FASs and PKSs,
      harbor acyltransferases (ATs), which select substrates for condensation by beta
      ketoacyl synthases (KSs). Here, we present the structural and functional
      characterization of the polyspecific malonyl/acetyltransferase (MAT) of murine
      FAS. We assign kinetic constants for the transacylation of the native substrates,
      acetyl- and malonyl-CoA, and demonstrate the promiscuity of FAS to accept
      structurally and chemically diverse CoA-esters. X-ray structural data of the KS
      MAT didomain in a malonyl-loaded state suggests a MAT-specific role of an active
      site arginine in transacylation. Owing to its enzymatic properties and its
      accessibility as a separate domain, MAT of murine FAS may serve as versatile tool
      for engineering PKSs to provide custom-tailored access to new polyketides that
      can be applied in antibiotic and antineoplastic therapy.

PMID- 29328620
TI  - Thermal Stability of Mixed Cation Metal Halide Perovskites in Air.
AB  - We study the thermal stability in air of the mixed cation organic-inorganic lead
      halide perovskites Cs0.17FA0.83Pb(I0.83Br0.17)3 and
      Cs0.05(MA0.17FA0.83)0.95Pb(I0.83Br0.17)3. For the latter compound, containing
      both MA+ and FA+ ions, thermal decomposition of the perovskite phase was observed
      to occur in two stages. The first stage of decomposition occurs at a faster rate
      compared to the second stage and is only observed at relatively low temperatures
      (T < 150  degrees C). For the second stage, we find that both decomposition rate
      and the activation energy have similar values for
      Cs0.05(MA0.17FA0.83)0.95Pb(I0.83Br0.17)3 and Cs0.17FA0.83Pb(I0.83Br0.17)3, which
      suggests that the first stage mainly involves reaction of MA+ and the second
      stage mainly FA+.

PMID- 29328621
TI  - Correction to Improved Synthesis of Graphene Oxide.

PMID- 29328623
TI  - Mimicking Biological Synaptic Functionality with an Indium Phosphide Synaptic
      Device on Silicon for Scalable Neuromorphic Computing.
AB  - Neuromorphic or "brain-like" computation is a leading candidate for efficient,
      fault-tolerant processing of large-scale data as well as real-time sensing and
      transduction of complex multivariate systems and networks such as self-driving
      vehicles or Internet of Things applications. In biology, the synapse serves as an
      active memory unit in the neural system and is the component responsible for
      learning and memory. Electronically emulating this element via a compact,
      scalable technology which can be integrated in a three-dimensional (3-D)
      architecture is critical for future implementations of neuromorphic processors.
      However, present day 3-D transistor implementations of synapses are typically
      based on low-mobility semiconductor channels or technologies that are not
      scalable. Here, we demonstrate a crystalline indium phosphide (InP)-based
      artificial synapse for spiking neural networks that exhibits elasticity, short
      term plasticity, long-term plasticity, metaplasticity, and spike timing-dependent
      plasticity, emulating the critical behaviors exhibited by biological synapses.
      Critically, we show that this crystalline InP device can be directly integrated
      via back-end processing on a Si wafer using a SiO2 buffer without the need for a
      crystalline seed, enabling neuromorphic devices that can be implemented in a
      scalable and 3-D architecture. Specifically, the device is a crystalline InP
      channel field-effect transistor that interacts with neuron spikes by modification
      of the population of filled traps in the MOS structure itself. Unlike other
      transistor-based implementations, we show that it is possible to mimic these
      biological functions without the use of external factors (e.g., surface
      adsorption of gas molecules) and without the need for the high electric fields
      necessary for traditional flash-based implementations. Finally, when exposed to
      neuronal spikes with a waveform similar to that observed in the brain, these
      devices exhibit the ability to learn without the need for any external
      potentiating/depressing circuits, mimicking the biological process of Hebbian
      learning.

PMID- 29328622
TI  - Laser-Induced Conversion of Teflon into Fluorinated Nanodiamonds or Fluorinated
      Graphene.
AB  - Laser-assisted materials fabrication is an advanced technique that has propelled
      recent carbon synthesis approaches. Direct laser writing on polyimide or
      lignocellulose materials by a CO2 laser has successfully transformed the
      substrates into hierarchical graphene. However, formation of other carbon
      allotropes such as diamond and fullerene remains challenging. Here, we report the
      direct synthesis of fluorinated nanodiamonds or fluorinated graphene by treating
      polytetrafluoroethylene (Teflon, or PTFE) with a 9.3 MUm pulsed CO2 laser under
      argon; no exogenous fluorine source is needed. The laser is part of a commercial
      laser cutting/scribing system that is found in most machine shops. Therefore, it
      is a readily accessible tool. This discovery could inspire future development for
      the laser-assisted synthesis of functionalized carbon allotropes.

PMID- 29328624
TI  - Secondary-Phase Stochastics in Lithium-Ion Battery Electrodes.
AB  - Lithium-ion battery electrodes exhibit complex interplay among multiple
      electrochemically coupled transport processes, which rely on the underlying
      functionality and relative arrangement of different constituent phases. The
      electrochemically inactive solid phases (e.g., conductive additive and binder,
      referred to as the secondary phase), while beneficial for improved electronic
      conductivity and mechanical integrity, may partially block the electrochemically
      active sites and introduce additional transport resistances in the pore
      (electrolyte) phase. In this work, the role of mesoscale interactions and
      inherent stochasticity in porous electrodes is elucidated in the context of short
      range (interface) and long-range (transport) characteristics. The electrode
      microstructure significantly affects kinetically and transport-limiting scenarios
      and thereby the cell performance. The secondary-phase morphology is also found to
      strongly influence the microstructure-transport-kinetics interactions. Apropos,
      strategies have been proposed for performance improvement via electrode
      microstructural modifications.

PMID- 29328625
TI  - Double-Channel Piezotronic Transistors for Highly Sensitive Pressure Sensing.
AB  - Piezotronic transistors (PTs) that utilize inner crystal potential generated by
      interface piezoelectric polarization charges as the gate voltage have great
      potential applications in force/pressure-triggered or controlled electronic
      devices, sensors, human-machine communication, and microelectromechanical
      systems. Although the performance of PTs has been partially enhanced by exploring
      special materials with different geometries or high piezoelectricity, few studies
      have been focused on the structure design of PT itself to more effectively
      enhance the performance and structural reliability. Here, an integrated double
      channel plane piezotronic transistor is invented as a high-performance pressure
      sensing technology. Owing to the double-channel modulation and the plane
      structure, the PT has the merits of high pressure sensitivity (84.2-104.4
      meV/MPa) and high structural reliability, which provides the opportunity for
      great applications, such as human-computer interfacing, biosensing, and health
      monitoring.

PMID- 29328626
TI  - Polystyrene-Core, Silica-Shell Scintillant Nanoparticles for Low-Energy
      Radionuclide Quantification in Aqueous Media.
AB  - beta-particle emitting radionuclides are useful molecular labels due to their
      abundance in biomolecules. Detection of beta-emission from 3H, 35S, and 33P,
      important biological isotopes, is challenging due to the low energies (Emax <=
      300 keV) and short penetration depths (<=0.6 mm) in aqueous media. The activity
      of biologically relevant beta-emitters is usually measured in liquid
      scintillation cocktail (LSC), a mixture of energy-absorbing organic solvents,
      surfactants, and scintillant fluorophores, which places significant limitations
      on the ability to acquire time-resolved measurements directly in aqueous
      biological systems. As an alternative to LSC, we developed polystyrene-core,
      silica-shell nanoparticle scintillators (referred to as nanoSCINT) for
      quantification of low-energy beta-particle emitting radionuclides directly in
      aqueous solutions. The polystyrene acts as an absorber for energy from emitted
      beta-particles and can be loaded with a range of hydrophobic scintillant
      fluorophores, leading to photon emission at visible wavelengths. The silica shell
      serves as a hydrophilic shield for the polystyrene core, enabling dispersion in
      aqueous media and providing better compatibility with water-soluble analytes.
      While polymer and inorganic scintillating microparticles are commercially
      available, their large size and/or high density complicates effective dispersion
      throughout the sample volume. In this work, nanoSCINT nanoparticles were prepared
      and characterized. nanoSCINT responds to 3H, 35S, and 33P directly in aqueous
      solutions, does not exhibit a change in scintillation response between pH 3.0 and
      9.5 or with 100 mM NaCl, and can be recovered and reused for activity
      measurements in bulk aqueous samples, demonstrating the potential for reduced
      production of LSC waste and reduced total waste volume during radionuclide
      quantification. The limits of detection for 1 mg/mL nanoSCINT are 130 nCi/mL for
      3H, 8 nCi/mL for 35S, and <1 nCi/mL for 33P.

PMID- 29328628
TI  - Analysis of Gluten in a Wheat-Gluten-Incurred Sorghum Beer Brewed in the Presence
      of Proline Endopeptidase by LC/MS/MS.
AB  - Most gluten-reduced beers are produced using an enzyme called proline
      endopeptidase (PEP), which proteolyzes the gluten by cleaving at proline
      residues. However, the gluten content of beers brewed in the presence of PEP
      cannot be verified since current analytical methods are not able to accurately
      quantitate gluten in fermented foods. In this work, mass spectrometry was used to
      qualitatively characterize the gluten in a wheat-gluten-incurred sorghum model
      beer brewed with and without the addition of PEP. Hydrolyzed gluten peptides and
      chymotryptic gluten peptides produced from intact gluten proteins were detected
      in beer brewed in the presence of up to 6 times the manufacturer's recommended
      dosage of PEP. The observation of chymotryptic gluten peptides indicates that
      some gluten proteins remained, at least partially, intact after fermentation and
      enzymatic treatment. Less intact gluten was observed in beer brewed in the
      presence of PEP, but more hydrolyzed gluten peptides were consequently observed
      in PEP-containing beer. Gluten peptides that contained immunogenic sequences
      known to be associated with celiac disease were detected in PEP-containing beer.

PMID- 29328627
TI  - Effect of Surface Chemistry and Associated Protein Corona on the Long-Term
      Biodegradation of Iron Oxide Nanoparticles In Vivo.
AB  - The protein corona formed on the surface of a nanoparticle in a biological medium
      determines its behavior in vivo. Herein, iron oxide nanoparticles containing the
      same core and shell, but bearing two different surface coatings, either glucose
      or poly(ethylene glycol), were evaluated. The nanoparticles' protein adsorption,
      in vitro degradation, and in vivo biodistribution and biotransformation over four
      months were investigated. Although both types of nanoparticles bound similar
      amounts of proteins in vitro, the differences in the protein corona composition
      correlated to the nanoparticles biodistribution in vivo. Interestingly, in vitro
      degradation studies demonstrated faster degradation for nanoparticles
      functionalized with glucose, whereas the in vivo results were opposite with
      accelerated biodegradation and clearance of the nanoparticles functionalized with
      poly(ethylene glycol). Therefore, the variation in the degradation rate observed
      in vivo could be related not only to the molecules attached to the surface, but
      also with the associated protein corona, as the key role of the adsorbed proteins
      on the magnetic core degradation has been demonstrated in vitro.

PMID- 29328629
TI  - Coupled Triboelectric Nanogenerator Networks for Efficient Water Wave Energy
      Harvesting.
AB  - Water wave energy is a promising clean energy source, which is abundant but hard
      to scavenge economically. Triboelectric nanogenerator (TENG) networks provide an
      effective approach toward massive harvesting of water wave energy in oceans. In
      this work, a coupling design in TENG networks for such purposes is reported. The
      charge output of the rationally linked units is over 10 times of that without
      linkage. TENG networks of three different connecting methods are fabricated and
      show better performance for the ones with flexible connections. The network is
      based on an optimized ball-shell structured TENG unit with high responsivity to
      small agitations. The dynamic behavior of single and multiple TENG units is also
      investigated comprehensively to fully understand their performance in water. The
      study shows that a rational design on the linkage among the units could be an
      effective strategy for TENG clusters to operate collaboratively for reaching a
      higher performance.

PMID- 29328631
TI  - Controllable Interfacial Coupling Effects on the Magnetic Dynamic Properties of
      Perpendicular [Co/Ni]5/Cu/TbCo Composite Thin Films.
AB  - Dynamic magnetic properties in perpendicularly exchange-coupled [Co/Ni]5/Cu (tCu
      = 0-2 nm)/TbCo structures show strong dependences on the interfacial
      antiferromagnetic strength Jex, which is controlled by the Cu interlayer
      thickness. The precession frequency f and effective damping constant alphaeff of
      a [Co/Ni]5 multilayer differ distinctly for parallel (P) and antiparallel (AP)
      magnetization orientation states. For samples with a thin tCu, f of the AP state
      is apparently higher, whereas alphaeff is lower than that in the P state, owing
      to the unidirectional exchange bias effect (HEB) from the TbCo layer. The
      differences in f and alphaeff between the two states gradually decrease with
      increasing tCu. By using a uniform precession model including an additional HEB
      term, the field-dependent frequency curves can be well-fitted, and the fitted HEB
      value is in good agreement with the experimental data. Moreover, the saturation
      damping constant alpha0 displays a nearly linear correlation with Jex. It
      decreases significantly with Jex and eventually approaches a constant value of
      0.027 at tCu = 2 nm where Jex vanishes. These results provide a better
      understanding and effective control of magnetization dynamics in exchange-coupled
      composite structures for spintronic applications.

PMID- 29328630
TI  - Effects of Secondary Phases on the High-Performance Colossal Permittivity in
      Titanium Dioxide Ceramics.
AB  - The intensive demands of microelectronics and energy-storage applications are
      driving the increasing investigations on the colossal permittivity (CP)
      materials. In this study, we designed a new system of Dy and Nb co-doped TiO2
      ceramics [(Dy0.5Nb0.5)xTi1-xO2] with the formation of secondary phases, and then
      the enhancement of overall dielectric properties (epsilonr ~ 5.0-6.5 * 104 and
      tan delta < 8%) was realized in the broad composition range of 0.5 <= x <= 5%.
      More importantly, effects of secondary phases on microstructure, dielectric
      properties, and stability were explored from the views of defect-dipoles and
      internal barrier layer capacitance (IBLC) effect. According to the defect-dipoles
      theory, the CP should mainly originate from Nb5+, and the Dy3+ largely
      contributes to the decreased dielectric loss. Both CP and low dielectric loss
      were obtained for co-doping with Dy3+ and Nb5+. Besides, the Dy enrichment
      induced the formation of secondary phases, which were regarded as the low loss
      unit dispersed into the ceramic matrix, and largely facilitate the decreased
      dielectric loss. In particular, the analysis of temperature-dependent complex
      impedance spectra indicated that a stronger IBLC effect caused by the increased
      grain boundary resistance can also contribute to the optimized CP and low
      dielectric loss under appropriate contents of secondary phases.

PMID- 29328632
TI  - Probing Growth-Induced Anisotropic Thermal Transport in High-Quality CVD Diamond
      Membranes by Multifrequency and Multiple-Spot-Size Time-Domain Thermoreflectance.
AB  - The maximum output power of GaN-based high-electron mobility transistors is
      limited by high channel temperature induced by localized self-heating, which
      degrades device performance and reliability. Chemical vapor deposition (CVD)
      diamond is an attractive candidate to aid in the extraction of this heat and in
      minimizing the peak operating temperatures of high-power electronics. Owing to
      its inhomogeneous structure, the thermal conductivity of CVD diamond varies along
      the growth direction and can differ between the in-plane and out-of-plane
      directions, resulting in a complex three-dimensional (3D) distribution. Depending
      on the thickness of the diamond and size of the electronic device, this 3D
      distribution may impact the effectiveness of CVD diamond in device thermal
      management. In this work, time-domain thermoreflectance is used to measure the
      anisotropic thermal conductivity of an 11.8 MUm-thick high-quality CVD diamond
      membrane from its nucleation side. Starting with a spot-size diameter larger than
      the thickness of the membrane, measurements are made at various modulation
      frequencies from 1.2 to 11.6 MHz to tune the heat penetration depth and sample
      the variation in thermal conductivity. We then analyze the data by creating a
      model with the membrane divided into ten sublayers and assume isotropic thermal
      conductivity in each sublayer. From this, we observe a two-dimensional gradient
      of the depth-dependent thermal conductivity for this membrane. The local thermal
      conductivity goes beyond 1000 W/(m K) when the distance from the nucleation
      interface only reaches 3 MUm. Additionally, by measuring the same region with a
      smaller spot size at multiple frequencies, the in-plane and cross-plane thermal
      conductivities are extracted. Through this use of multiple spot sizes and
      modulation frequencies, the 3D anisotropic thermal conductivity of CVD diamond
      membrane is experimentally obtained by fitting the experimental data to a thermal
      model. This work provides an improved understanding of thermal conductivity
      inhomogeneity in high-quality CVD polycrystalline diamond that is important for
      applications in the thermal management of high-power electronics.

PMID- 29328633
TI  - Size-Induced Segregation in the Stepwise Microhydration of Hydantoin and Its Role
      in Proton-Induced Charge Transfer.
AB  - Recent photochemistry experiments provided evidence for the formation of
      hydantoin by irradiation of interstellar ice analogues. The significance of these
      results and the importance of hydantoin in prebiotic chemistry and polypeptide
      synthesis motivate the present theoretical investigation, in which we analyzed
      the effects of stepwise hydration on the electronic and thermodynamical
      properties of the structure of microhydrated hydantoin using a variety of
      computational approaches. We generally find microhydration to proceed around the
      hydantoin heterocycle until 5 water molecules are reached, at which stage
      hydration becomes segregated with a water cluster forming aside the heterocycle.
      The reactivity of microhydrated hydantoin caused by an impinging proton was
      evaluated through charge transfer collision cross sections for microhydrated
      compounds but also for hydantoin on icy grains modeled using a cluster approach
      mimicking the true hexagonal ice surface. The effects of hydration on charge
      transfer efficiency are mostly significant when few water molecules are present,
      and they progressively weaken and stabilize in larger clusters. On the ice
      substrate, charge transfer essentially contributes to a global increase in the
      cross sections.

PMID- 29328634
TI  - Exploring the Rich Potential Energy Surface of (H2O)11 and Its Physical
      Implications.
AB  - The rich potential energy surface of the water undecamer (H2O)11 was explored
      with a basin hopping algorithm using a TIP4P potential and other methods followed
      by extensive ab initio MP2 minimizations and CCSD(T) corrections. This protocol
      yielded 17, 66, and 125 distinct isomers within 0.5, 1.0, and 2.0 kcal mol-1 of
      the complete basis set CCSD(T) global minimum, respectively. These isomers were
      categorized into 15 different families based on their oxygen framework and
      hydrogen bonding topology. Determination of the global minimum proved challenging
      because of the presence of many nearly isoenergetic isomers. The predicted global
      minimum varied among ab initio methods, density functionals, and model
      potentials, and it was sensitive to the choice of energy extrapolation schemes,
      higher-order CCSD(T) corrections, and inclusion of zero-point vibrational energy.
      The presence of a large number of nearly degenerate structures and the
      isomerization between them has manifested itself in the anomalous broadening of
      the heat capacity curve of the undecamer in simulations around the melting
      region.

PMID- 29328635
TI  - Adsorption and Molecular Fractionation of Dissolved Organic Matter on Iron
      Bearing Mineral Matrices of Varying Crystallinity.
AB  - Iron (Fe)-bearing mineral phases contribute disproportionately to adsorption of
      soil organic matter (SOM) due to their elevated chemical reactivity and specific
      surface area (SSA). However, the spectrum of Fe solid-phase speciation present in
      oxidation-reduction-active soils challenges analysis of SOM-mineral interactions
      and may induce differential molecular fractionation of dissolved organic matter
      (DOM). This work used paired selective dissolution experiments and batch sorption
      of postextraction residues to (1) quantify the contributions of Fe-bearing
      minerals of varying crystallinity to DOM sorption, and (2) characterize molecular
      fractionation using Fourier transform ion cyclotron resonance mass spectrometry
      (FT-ICR-MS). A substantial proportion of soil SSA was derived from extracted Fe
      bearing phases, and FT-ICR-MS analysis of extracted DOM revealed distinct
      chemical signatures across Fe-OM associations. Sorbed carbon (C) was highly
      correlated with Fe concentrations, suggesting that Fe-bearing phases are strong
      drivers of sorption in these soils. Molecular fractionation was observed across
      treatments, particularly those dominated by short-range-order (SRO) mineral
      phases, which preferentially adsorbed aromatic and lignin-like formulas, and
      higher-crystallinity phases, associated with aliphatic DOM. These findings
      suggest Fe speciation-mediated complexation acts as a physicochemical filter of
      DOM moving through the critical zone, an important observation as predicted
      changes in precipitation may dynamically alter Fe crystallinity and C stability.

PMID- 29328636
TI  - Relapse of Takayasu arteritis as a cause of suicidal poisoning and subsequent
      major ischemic stroke successfully treated with thrombolytic therapy.
AB  - Introduction: Takayasu arteritis (TA) is a rare large vessel arteritis, affecting
      primarily aorta and its major branches. Its clinical manifestations can vary
      significantly - from asymptomatic to serious vascular events. Acute neurological
      complications are frequent at the onset of the disease and in relapses. Anxiety
      and depression are more frequent in TA patients than in general population as
      well as during relapses. Prevalence of transient ischemic attack or ischemic
      stroke in TA patients is approximately 10-20%. Case report: We presented a
      patient with TA that began with a depressive episode resulting in attempted
      suicide by bromazepame poisoning. This was subsequently followed by major
      ischemic stroke caused by thrombosis of the left middle cerebral artery (probably
      due to aortic arch embolism) successfully treated with intravenous thrombolysis.
      Conclusion: Intravenous thrombolysis appears to be safe and effective in patients
      with TA and stroke.

PMID- 29328637
TI  - Alp Rose stem cells, olive oil squalene and a natural alkyl polyglucoside
      emulsifier: Are they appropriate ingredients of skin moisturizers - in vivo
      efficacy on normal and sodium lauryl sulfate - irritated skin?.
AB  - Background/Aim: Since skin moisturization may be achieved by both actives and
      chosen carrier, plant stem cells, squalene and natural alkyl polyglucoside
      emulsifier may be potential components of contemporary cosmetic products. The aim
      of the study was in vivo evaluation of the skin irritation potential and the
      efficacy of Alpine Rose stem cells incorporated into li-posomes and olive oil
      squalene as ingredients of moisturizing creams, with respect to the novel
      emulsifier used for creams' stabilization. Methods: With the employment of
      noninvasive skin biophysical measurements, skin hydration (EC), transepi-dermal
      water loss (TEWL), erythema index (EI) and viscoelas-ticity were measured on 76
      healthy volunteers. In the first phase, skin irritation after a 24-hour occlusion
      and the long-term efficacy of creams (a 21-day study) on healthy skin were
      evaluated. Phase II of the study focused on the cream efficacy assessment after a
      6-day treatment of sodium lauryl sulfate-irritated skin. Results: After a 24-hour
      occlusion, there were no significant changes in the EI for any tested sample. In
      the second phase of the study, the EI was not significantly altered for the cream
      containing squalene, while the application of all active samples resulted in a
      significant reduction of TEWL. In both phases of the study an EC increase was
      recorded, espe-cially for the squalene-containing cream. Conclusion: Due to the
      lack of skin irritation and skin barrier impairment along with the marked
      hydration effect, it could be said that the in-vestigated actives incorporated
      into alkyl polyglucoside emulsi-fier-stabilized creams may be safely applied as
      ingredients for "tailor-made" cosmetic moisturizers intended for normal and dry
      skin care, whereas olive oil squalene could be used for the treatment of
      irritated or sensitive skin as well. [Projekat Ministarstva nauke Republike
      Srbije, br. TR34031]

PMID- 29328638
TI  - Cataract, ocular surgery, aphakia, and the chromatic expression of the painter
      Jovan Bijelic.
AB  - Background/Aim: Approaching art from the standpoint of optics and the artist's
      eye pathology can sometimes explain the shift of the spectral colors in the work
      of some artists with cataract and aphakia. This may not be obvious in the
      paintings of other artists with the same eye pathology. The aim of this study was
      to create a timeline from the recently obtained details of the cataract surgery,
      his best corrected aphakic visual acuity, and the last paintings of the artist
      Jovan Bijelic. Methods: The research included primary and secondary source
      material: Bijelic's paintings from all stages of his career, interviews with
      Bijelic and his eye surgeon, art criticism, sources with the description of
      Bijelic's symptoms, hospital archives, discussion with art historians, comparison
      of his palette from different periods. Results: Jovan Bijelic was nearly blind
      from cataract in 1957. He underwent an unsuccessful cataract surgery in 1956,
      followed by enucleation of the operated eye. In 1958, 20/25-20/20 vision was
      regained, after the extracapsular cataract extraction and sector iridectomy in
      his right eye, with the posterior lens capsule discision afterwards. Xanthopsia
      and cyanopsia are not present in his art, which is not a representation of
      visualized objects. Conclusion: The response of Jovan Bijelic to cataract and
      aphakia was predominantly a change of his style.

PMID- 29328639
TI  - The use of hyaluronic and aminocaproic acid in the treatment of alveolar
      osteitis.
AB  - Background/Aim: Alveolar osteitis (AO), also known as "dry socket", is relatively
      common post-extraction complication. It probably occurs due to excessive
      fibrinolytic activity in the coagulum and is characterized by intense pain
      sensations. The aim of this clinical study was to examine the role of hyaluronic
      acid and aminocaproic acid in the treatment of AO. Methods: The study included 60
      patients with the clinical diagnosis of AO. All the patients were divided into
      two groups of 30 patients each according to the applied non-pharmacological
      measure: irrigation - irrigation of dry socket with sterile saline; curettage -
      careful curettage. Both of these groups were further divided into three subgroups
      regarding the applied treatment (hyaluronic acid; hyaluronic acid + aminocaproic
      acid; Alvogyl (r), an anesthetic and antiseptic paste), each with 10 patients,
      according to the following protocol: 0.2 mL of hyaluronic acid in the form of a
      0.8% gel; 2 mL of aminocaproic acid and hyaluronic acid; Alvogyl(r). During each
      visit, scheduled for every two days until complete absence of painful sensations,
      the patients had the therapeutic method repeated as at the first examination. At
      each control visit the number of present symptoms and signs of AO was recorded,
      as well as the level of pain (measured with a visual analogue scale). Results:
      With the use of hyaluronic acid, with or without aminocaproic one, a
      statistically significantly faster reduction in pain sensations was achieved,
      along with the reduction in the number of symptoms and signs of AO compared to
      the use of Alvogyl(r). Conclusion: Hyaluronic acid, applied alone or in
      combination with aminocaproic acid significantly reduces pain sensation, thus it
      can be successfully used in the treatment of AO.

PMID- 29328640
TI  - Prevalence of metabolic syndrome in Montenegrin patients with psoriasis.
AB  - Background/Aim: Increasing epidemiological studies suggest the association
      between psoriasis and metabolic syndrome. The aim of this study was to assess the
      association of metabolic syndrome and its components with psoriasis in a sample
      of patients from Montenegro, and to predict the factors that determine the
      metabolic syndrome. Methods: A case-control study was conducted at the Clinic of
      Dermatology and Venereology, Clinical Center of Montenegro, Podgorica,
      Montenegro, between January and December 2012. The study group included 101
      patients with psoriasis (cases) and 126 patients with the diagnosis of
      dermatological disease other than psoriasis (controls) consecutively admitted to
      the same clinic. Results: Metabolic syndrome was more prevalent in the psoriasis
      patients than in the controls (48.5% vs 20.6%; OR = 2.99). In addition, the
      psoriasis patients were significantly more likely to be smokers (OR = 2.16) and
      were less physically active (OR = 0.58). Conclusion: The results of this study
      demonstrate a strong association between psoriasis and metabolic syndrome
      independent of psoriasis severity. Patients with psoriasis should be routinely
      screened for metabolic syndrome and its components. [Projekat Ministarstva nauke
      Republike Srbije, br. 175025: Clinical-epidemiological research of diseases of
      public health importance in Serbia].

PMID- 29328641
TI  - Correlation of local and systemic expression of survivin with histopathological
      parameters of cutaneous melanoma.
AB  - Background/Aim: Survivin is a multifunctional protein abundantly expressed in
      tumors of various types, including melanoma. There are still sparse data
      regarding relationship of melanoma cell survivin expression with accepted
      histopathological characteristics as well as serum concentration. The aim of this
      study was to investigate the association of local tumor survivin expression
      (primary tumor and metastatic lesions) and serum concentration with clinical and
      histopathological parameters in melanoma patients. Methods: The level of survivin
      expression was determined immunocytochemically in tumor tissue and with ELISA
      test in the serum of 84 melanoma patients diagnosed from 2009 to 2013 at the
      Institute for Pathology and Forensic Medicine and Institute for Medical Research
      at Military Medical Academy, Belgrade, Serbia. Results: The intensity of survivin
      expression was significantly higher in the patients whose tumor had ulceration,
      higher mitotic index, higher Clark and Breslow stage, that made vascular invasion
      or spread through lymphatic vessels in primary tumor, and was significantly
      higher in the patients with metastatic disease. Survivin expression and the
      number of survivin positive cells in metastatic lesions were significantly
      associated with the duration of disease free interval (DFI). The patients with
      high expression score had almost double shorter DFI comparing to those with weak
      local survivin expression and a small number of survivin+cells (9 +/- 7 vs 19 +/-
      13 months, respectively). The degree of tumor infiltrating lymphocytes presence
      in tumor tissue was significantly associated with serum survivin concentration,
      with lowest average level detected in samples of patients with the highest degree
      of infiltration. Serum survivin concentrations were highest in samples of
      melanoma patients with IA American Joint Commission on Cancer (AJCC) clinical
      stage, pT1a histological stage, patients whose tumors were still in horizontal
      growth phase, without signs of lympho-hematological disease spreading, with the
      highest number of mitoses and the smallest Clark index. Conclusion: Survivin
      expression in tumor tissue and its serum concetration significantly correlate
      with clinical and histopathological parameters. Serum levels could be important
      in initial follow-up as indicators of those patients that would have aggressive
      local tumor growth and spreading. Survivin determination in tumor tissue is of
      great significance in estimation of DFI.

PMID- 29328642
TI  - The effects of industrial noise of higher spectrum on the workers' auditory
      perception abilities.
AB  - Background/Aim: Results of previous studies gave support to the idea that
      machines in power plants produce noise of different levels of loudness and
      frequency, and that it could cause deterioration of the hearing ability of
      workers. As a matter of fact, noiseinduced hearing loss is the most widespread
      occupational disease nowadays. As noise is a complex acoustic phenomenon, more
      factors have to be considered when studying it, such as frequency, intensity and
      the period of exposure. The aim of this study was to find if there are
      differences in the absolute threshold of hearing between workers in the factory
      production lines that are constantly exposed to the industrial noise of higher
      spectrum and those exposed to the noise of standard spectrum at different
      frequencies of sound. Methods: In the research plan, there were 308 workers
      employed in the production line of the Factory "Knjaz Milos", Arandelovac. A
      total of 205 of them were working in the conditions of higher spectrum noise
      (4,000 Hz - 8,000 Hz) and 103 workers were exposed to standard noise spectrum
      (31.5 Hz - 2,000.0 Hz). The objective measures of noise (frequency and amplitude)
      were acquired by phonometer, and measures of absolute threshold of hearing for
      both ears were obtained by audiometer by exposure to nine sound frequency levels.
      Data were statistically analyzed by establishing the significance of differences
      between absolute thresholds of hearing for both groups and for all nine frequency
      levels. Results: It was found that the absolute threshold of hearing is
      significantly higher for the group exposed to highfrequency noise at the 4,000 Hz
      and 8,000 Hz levels of frequency. Conclusion: Reduction of hearing sensitivity is
      evident for those exposed to higher spectrum noise, which is particularly evident
      at the higher frequency levels. Employees are often unaware of its effects
      because they are the results of prolonged exposure. Therefore, working in those
      conditions requires preventive measures and regular testing of the hearing
      ability.

PMID- 29328643
TI  - Disturbance of oxidative balance in the first trimester of spontaneous abortions.
AB  - Background/Aim: Pregnancy is defined as a condition of increased oxidative
      stress. The aim of this research was to determine the intensity of pro-oxidative
      processes and the content of GSH, as well as antioxidative enzymes: superoxide
      dismutase (SOD), catalase (CAT), gluthatione peroxidase (GSH-Px), and the total
      antioxidative status (TAS) in patients with spontaneous abortions. Methods: A
      total of 120 patients were involved in the research (70 spontaneous abortions and
      50 healthy pregnancies). The patients were divided into groups: 35 patients with
      incomplete and complete spontaneous abortion (group S), 35 patients with missed
      abortion (group M) and a control group of 50 healthy pregnancies (group N), all
      of them being in the first trimester of pregnancy. The intensity of lipid
      proxidation (LPx) was determined with a modified thyobarbituric acid method. The
      GSH content in erythrocytes was determined by the method ba-sed on the amount of
      non-protein sulfhydryl residues using the Ellman's reagens. The following
      antioxidative parameters in the blood were measured: SOD - by the method with
      xanthine oxidase-using commercial RANSOD sets; CAT - by the method of Aebi (the
      enzyme activity was measured by monitoring the decomposition of H2O2 at 240 nm);
      GSH-Px was determined using hydrogen peroxide as a substrate. The TAS was
      determined using the ferric reducing autioxidant potential (FRAP) met-hod.
      Results: The highest average value of LPx was recorded in the spontaneous
      abortion group (48.03 pmoL/mg Hgb), and the lowest value was recorded in the
      control group (26.06 pmoL/mg Hgb). A statistically significant positive
      correlation between LPx and CAT in the group of patients with missed abortion was
      also noted (p < 0.05, r = 0.37). There was a statistically highly significant
      difference (p < 0.001) in SOD and in CAT activitices be-tween the examined
      patients (groups S and N) and the control group (Student's t-test and ANOVA). The
      highest average value of TAS was recorded in the group S (710.39 MUmol/L), while
      the value in the group M was 277.66 MUmol/L. The average value of TAS in the
      control group was 452.12 MUmol/L. Student's t-test showed a statistically highly
      significant difference in the values of TAS between the examined patients (groups
      S and M) and the control group. Conclusion: Determination of the value of pro
      oxidative and antioxidative parameters in patients with sponta-neous abortion can
      be the indicator of condition of fetoplacental unit and these analyses can be
      included in the protocol of the rutine perinatal diagnostics.

PMID- 29328644
TI  - Can probiotics improve efficiency and safety profile of triple Helicobacter
      pylori eradication therapy? A prospective randomized study.
AB  - Background/Aim: Some studies suggest the benefit of applying different probiotic
      strains in combination with antibiotics in the eradication of Helicobacter pylori
      (H. pylori) infection. The aim of this study was to evaluate the effect of co
      administration of multiple probiotic strains with triple H. pylori eradication
      therapy. : This prospective study included 167 patients with dyspeptic symptoms
      and chronic gastritis who were diagnosed with H. pylori infection and randomized
      into two groups. The group I of 77 patients underwent triple eradication therapy,
      for 7 days, with lansoprazole, 2 * 30 mg half an hour before the meal,
      amoxicillin 2 * 1.000 mg per 12 hours and clarithromycin 2 * 500 mg per 12 hours.
      After the 7th day of the therapy, lansoprazole continued at a dose of 30 mg for
      half an hour before breakfast for 4 weeks. The group II of 90 patients received
      the same treatment as the patients of the group I, with the addition of the
      probiotic cultures in the form of a capsule comprising Lactobacillus Rosell-52,
      Lactobacillus Rosell-11, Bifidobacterium Rosell-1755 and Saccharomyces boulardii,
      since the beginning of eradication for 4 weeks. Eradication of H. pylori
      infection control was performed 8 weeks after the therapy by rapid urease test
      and histopathologic evaluation of endoscopic biopsies or by stool antigen test
      for H. pylori. : Eradication of H. pylori infection was achieved in 93.3% of the
      patients who received probiotics with eradication therapy and in 81.8% of
      patients who were only on eradication therapy without probiotics. The difference
      in eradication success was statistically significant, (p < 0.05). The incidence
      of adverse effects of eradication therapy was higher in the group of patients who
      were not on probiotic (28.6%) than in the group that received probiotic (17.7%),
      but the difference was not statistically significant. : Multiple probiotic
      strains addition to triple eradication therapy of H. pylori achieves a
      significantly better eradication success, with fewer side effects of antibiotics.

PMID- 29328645
TI  - Assessing Intermolecular Interactions in Guest-Free Clathrate Hydrate Systems.
AB  - Recently, empty hydrate structures sI, sII, sH, and others have been proposed as
      low-density ice structures by both experimental observations and computer
      simulations. Some of them have been synthesized in the laboratory, which
      motivates further investigations on the stability of such guest-free clathrate
      structures. Using semiempirical and ab initio-based water models, as well as
      dispersion-corrected density functional theory approaches, we predict their
      stability, including cooperative many-body effects, in comparison with reference
      data from converged wave function-based DF-MP2 electronic structure calculations.
      We show that large basis sets and counterpoise corrections are required to
      improve convergence in the interaction/binding energies for such systems.
      Therefore, extrapolation schemes based on triple/quadruple and
      quadruple/quintuple zeta quality basis sets are used to reach high accuracy.
      Eleven different water structures corresponding to dodecahedron, edge sharing,
      face sharing, and fused cubes, as a part of the WATER27 database, as well as
      cavities from the sI, sII, and sH clathrate hydrates formed by 20, 24, 28, and 36
      water molecules, are employed, and new benchmark energies are reported. Using
      these benchmark sets of interaction energies, we assess the performance of both
      analytical models and direct DFT calculations for such clathrate-like systems. In
      particular, seven popular water models (TIP4P/ice, TIP4P/2005, q-TIP4P/F, TTM2-F,
      TTM3-F, TTM4-F, and MB-pol) available in the literature, and nine density
      functional approximations (3 meta-GGAs, 3 hybrids, and 3 range separated
      functionals) are used to investigate their accuracy. By including dispersion
      corrections, our results show that errors in the interaction energies are reduced
      for most of the DFT functionals. Despite the difficulties faced by current water
      models and DFT functionals to accurately describe the interactions in such water
      systems, we found some general trends that could serve to extend their
      applicability to larger systems.

PMID- 29328646
TI  - Vibrational Properties of Bulk Boric Acid 2A and 3T Polymorphs and Their Two
      Dimensional Layers: Measurements and Density Functional Theory Calculations.
AB  - Boric acid (H3BO3) is being used effectively nowadays in traps/baits for the
      management of Aedes aegypti L. and Aedes albopictus Skuse species of mosquitoes,
      which are the main spreading vectors worldwide for diseases such as malaria,
      dengue, and zika. Previously, we published results on the structural, electronic,
      and optical properties of its molecular triclinic H3BO3-2A and trigonal H3BO3-3T
      polymorphs within the framework of density functional theory (DFT). Because of
      the renewed importance of these materials, the focus of this work is on the
      vibrational properties of the bulk boric acid 2A and 3T polymorphs. We measured
      the infrared and Raman spectra of the former, which was accompanied and
      interpreted through state-of-the-art DFT calculations, supplemented by
      computations regarding the H3BO3 molecule and two-dimensional layers based on the
      bulk structures. We identify/assign their normal modes and find vibrational
      signatures for each polymorph as well as in- and out-of-plane motions and
      molecular vibrations, unveiling a nice agreement between the DFT level of theory
      employed and our improved spectroscopic measurements in the wavenumber ranges of
      400-2000 cm-1 (infrared) and 0-1500 cm-1 (Raman). We show that a dispersion
      corrected DFT functional within the generalized gradient approximation (GGA) can
      be very accurate in describing the vibrational properties of the boric acid
      polymorphs. Besides, several issues left open/not clearly resolved in previously
      published works on the vibrational mode assignments of the bulk and 2D sheets of
      boric acid are explained satisfactorily. Finally, phonon dispersions and
      associated densities of states were also evaluated for each polymorph along with
      their temperature-dependent DFT-calculated entropy, enthalpy, free energy, heat
      capacity, and Debye temperature. In particular, our DFT calculations suggest a
      possible way to differentiate the 2A and 3T boric acid polymorphs through Raman
      spectroscopy and heat capacity measurements.

PMID- 29328647
TI  - Development of Yam Dioscorin-Loaded Nanoparticles for Paracellular Transport
      Across Human Intestinal Caco-2 Cell Monolayers.
AB  - Dioscorins, the major storage proteins of yam tubers, exert immunomodulatory
      activities. To improve oral bioavailability of dioscorins in the intestine,
      recombinant dioscorin (rDioscorin) was coated with N,N,N-trimethyl chitosan (TMC)
      and tripolyphosphate (TPP), resulting in the formation of TMC-rDio-TPP
      nanoparticles (NPs). The loading capacity and entrapment efficiency of rDioscorin
      in the NPs were 26 +/- 0.7% and 61 +/- 1.4%, respectively. The NPs demonstrated a
      substantial release profile in the pH environment of the jejunum. The rDioscorin
      released from the NPs stimulated proliferation and phagocytosis of the macrophage
      RAW264.7 and activated the gene expression of IL-1beta and IL-6. Incubation of
      the NPs in the Caco-2 cell monolayer led to a 5.2-fold increase of Papp compared
      with rDioscorin alone, suggesting that rDioscorin, with the assistance of TMC,
      can be promptly transported across the intestinal epithelia. These results
      demonstrate that the TMC-rDio-TPP NPs can be utilized for elucidating the
      immunopharmacological effects of dioscorins through oral delivery.

PMID- 29328648
TI  - Two-Step Synthesis and Surface Modification of CaZnOS:Mn2+ Phosphors and the
      Fabrication of a Luminescent Poly(dimethylsiloxane) Film.
AB  - The CaZnOS:Mn2+ (CZOSM) phosphor has been extensively studied for its excellent
      optical performance, with a typical red emission band peaking at about 580 nm
      ascribed to the 4T1(4G)-6A1(6S) transition of Mn2+. Herein the CZOSM phosphor was
      synthesized by a novel two-step method accompanied by control of the morphology
      of the precursor in the first step followed by sintering in the second step,
      which demonstrated improved emission intensity and uniform morphology
      simultaneously compared to those obtained by the traditional solid-state reaction
      route. Thus, uniform ZnS:Mn2+ particles could be obtained by a hydrothermal
      method, and then a Ca(OH)2 shell was coated onto the ZnS:Mn2+ particles via a
      precipitation reaction. After that, these mixtures were sintered at the optimum
      temperature 800  degrees C in an argon atmosphere to prepare the CZOSM particles.
      Oleic acid (OA) was further used to transfer the hydrophilic CZOSM phosphors to
      hydrophobic ones. Finally, luminescent poly(dimethylsiloxane) (PDMS) films were
      fabricated by using the hydrophobic CZOSM@OA powders, and their optical
      performance and flexibility were evaluated. Our results provide insight into the
      synthesis of hydrophobic phosphor particles used in luminescent PDMS films and
      help to unravel their potential application for flexible optical devices.

PMID- 29328649
TI  - Phenylthiomethyl Ketone-Based Fragments Show Selective and Irreversible
      Inhibition of Enteroviral 3C Proteases.
AB  - Lead structure discovery mainly focuses on the identification of noncovalently
      binding ligands. Covalent linkage, however, is an essential binding mechanism for
      a multitude of successfully marketed drugs, although discovered by serendipity in
      most cases. We present a concept for the design of fragments covalently binding
      to proteases. Covalent linkage enables fragment binding unrelated to affinity to
      shallow protein binding sites and at the same time allows differentiated targeted
      hit verification and binding location verification through mass spectrometry. We
      describe a systematic and rational computational approach for the identification
      of covalently binding fragments from compound collections inhibiting enteroviral
      3C protease, a target with high therapeutic potential. By implementing reactive
      groups potentially forming covalent bonds as a chemical feature in our 3D
      pharmacophore methodology, covalent binders were discovered by high-throughput
      virtual screening. We present careful experimental validation of the virtual hits
      using enzymatic assays and mass spectrometry unraveling a novel, previously
      unknown irreversible inhibition of the 3C protease by phenylthiomethyl ketone
      based fragments. Subsequent synthetic optimization through fragment growing and
      reactivity analysis against catalytic and noncatalytic cysteines revealed
      specific irreversible 3C protease inhibition.

PMID- 29328650
TI  - Evidence for Indirect Action of Ionizing Radiation in 18-Crown-6 Complexes with
      Halogenous Salts of Strontium: Simulation of Radiation-Induced Transformations in
      Ionic Liquid/Crown Ether Compositions.
AB  - Ionic liquid/crown ether compositions are an attractive alternative to
      traditional extractants in the processes for spent nuclear fuel and liquid
      radioactive wastes reprocessing. These compositions are exposed to ionizing
      radiation, and their radiation stability, especially in the presence of metal
      salts, is a crucial issue. In the present study, the macrocyclic 18C6.Sr(BF4)2
      and 18C6.Sr(PF6)2 complexes simulating the components of metal loaded ionic
      liquid/crown ether extractants were synthesized and their structures were
      characterized by FTIR spectroscopy and single-crystal X-ray diffraction analysis.
      Inclusion of Sr2+ cation into the 18C6 cavity resulted in more symmetric D3d
      conformations of the macrocycle. The structural transformations of the crown
      ether were accompanied by an elongation of polyether C-O bonds that could
      increase the possibility of radiolytic cleavage of the macrocycle. However, EPR
      study of the synthesized compounds subjected to X-ray irradiation revealed
      predominant formation of macrocyclic -CH2-CH-O- radicals. This result
      demonstrated an evidence for indirect action of ionizing radiation on individual
      components of the complexes and was reasonably described by a positive "hole"
      transfer from primary macrocyclic radical cation to fluorous anion at the primary
      stages of radiolysis and a subsequent interaction of fluorine atom with 18C6
      macrocycle in secondary radical reactions. The observed effects may be partially
      responsible for enhanced sensitivity of the ionic liquid/crown ether extractants
      to ionizing radiation due to chemical blocking of the crown ether with radiolytic
      HF, radiation-chemical degradation of the 18C6, and precipitation of a low
      soluble SrF2.

PMID- 29328652
TI  - Trade-Induced Atmospheric Mercury Deposition over China and Implications for
      Demand-Side Controls.
AB  - Mercury (Hg) is of global concern because of its adverse effects on humans and
      the environment. In addition to long-range atmospheric transport, Hg emissions
      can be geographically relocated through economic trade. Here, we investigate the
      effect of China's interregional trade on atmospheric Hg deposition over China,
      using an atmospheric transport model and multiregional input-output analysis. In
      general, total atmospheric Hg deposition over China is 408.8 Mg yr-1, and 32% of
      this is embodied in China's interregional trade, with the hotspots occurring over
      Gansu, Henan, Hebei, and Yunnan provinces. Interprovincial trade considerably
      redistributes atmospheric Hg deposition over China, with a range in deposition
      flux from -104% to +28%. Developed regions, such as the Yangtze River Delta
      (Shanghai, Jiangsu, and Zhejiang) and Guangdong, avoid Hg deposition over their
      geographical boundaries, instead causing additional Hg deposition over developing
      provinces. Bilateral interaction among provinces is strong over some regions,
      suggesting a need for joint mitigation, such as the Jing-Jin-Ji region (Beijing,
      Tianjin, and Hebei) and the Yangtze River Delta. Transferring advanced technology
      from developed regions to their developing trade partners would be an effective
      measure to mitigate China's Hg pollution. Our findings are relevant to
      interprovincial efforts to reduce trans-boundary Hg pollution in China.

PMID- 29328651
TI  - Enzymatic Cleavage of Branched Peptides for Targeting Mitochondria.
AB  - Most of the reported mitochondria-targeting molecules are lipophilic and
      cationic, and thus they may become cytotoxic with accumulation. Here we show
      enzymatic cleavage of branched peptides that carry negative charges for targeting
      mitochondria. Conjugating a well-established protein tag (i.e., FLAG-tag) to self
      assembling motifs affords the precursors that form micelles. Enzymatic cleavage
      of the hydrophilic FLAG motif (DDDDK) by enterokinase (ENTK) turns the micelles
      to nanofibers. After being taken up by cells, the micelles, upon the action of
      intracellular ENTK, turn into nanofibers to locate mainly at mitochondria. The
      micelles of the precursors are able to deliver cargos (either small molecules or
      proteins) into cells, largely to mitochondria and within 2 h. Preventing ENTK
      proteolysis diminishes mitochondria targeting. As the first report of using
      enzymatic self-assembly for targeting mitochondria and delivery cargos to
      mitochondria, this work illustrates a fundamentally new way to target subcellular
      organelles for biomedicine.

PMID- 29328654
TI  - Country-Level Life Cycle Assessment of Greenhouse Gas Emissions from Liquefied
      Natural Gas Trade for Electricity Generation.
AB  - In the determination of the net impact of liquefied natural gas (LNG) on
      greenhouse gas emissions, life cycle assessments (LCA) of electricity generation
      have yet to combine the effects of transport distances between exporting and
      importing countries, country-level infrastructure in importing countries, and the
      fuel sources displaced in importing countries. To address this, we conduct a LCA
      of electricity generated from LNG export from British Columbia, Canada with a
      three-step approach: (1) a review of viable electricity generation markets for
      LNG, (2) the development of results for greenhouse gas emissions that account for
      transport to importing nations as well as the infrastructure required for power
      generation and delivery, and (3) emissions displacement scenarios to test
      assumptions about what electricity is being displaced in the importing nation.
      Results show that while the ultimate magnitude of the greenhouse gas emissions
      associated with natural gas production systems is still unknown, life cycle
      greenhouse gas emissions depend on country-level infrastructure (specifically,
      the efficiency of the generation fleet, transmission and distribution losses and
      LNG ocean transport distances) as well as the assumptions on what is displaced in
      the domestic electricity generation mix. Exogenous events such as the Fukushima
      nuclear disaster have unanticipated effects on the emissions displacement
      results. We highlight national regulations, environmental policies, and
      multilateral agreements that could play a role in mitigating emissions.

PMID- 29328653
TI  - Extending Half Life of H-Ferritin Nanoparticle by Fusing Albumin Binding Domain
      for Doxorubicin Encapsulation.
AB  - Nanoparticles based on the heavy chain of the human ferritin (HFn) are arousing
      growing interest in the field of drug delivery due to their exceptional
      characteristics. However, the unsatisfied plasma half life of HFn substantially
      limits its application as a delivery platform for antitumor agents. Herein we
      fused an albumin binding domain (ABD) variant that basically derives from the
      streptococcal protein G and possesses a long-acting characteristic in serum
      albumin to the N-terminus of the HFn for the aim of half-life extension. This ABD
      HFn construct was highly expressed and fully self-assembled into symmetrical and
      spherical structure in E. coli bacteria. The purified ABD-HFn showed a similar
      particle size with wild-type HFn and also exhibited an extremely high binding
      affinity with human serum albumin. To evaluate the therapeutic potential of this
      ABD-HFn construct in terms of half-life extension, we encapsulated a model
      antitumor agent doxorubicin (DOX) into the ABD-HFn. Significantly outstanding
      loading efficacy of above 60 molecules doxorubicin for each ABD-HFn cage was
      achieved. The doxorubicin-loaded ABD-HFn nanoparticle was characterized and
      further compared with the recombinant HFn counterpart. The ABD-HFn/DOX
      nanoparticle showed dramatically improved stability and comparable cell uptake
      rate when compared with HFn/DOX counterpart. Pharmacokinetics study in Sprague
      Dawley rats showed that ABD-HFn/DOX nanoparticle possessed significantly
      prolonged plasma half life of ~17.2 h, exhibiting nearly 19 times longer than
      that of free doxorubicin and 12 times for HFn/DOX. These optimal results
      indicated that fusion with ABD will be a promising strategy to extend the half
      life for protein-based nanoparticles.

PMID- 29328656
TI  - Design and Synthesis of Novel Reactive Oxygen Species Inducers for the Treatment
      of Pancreatic Ductal Adenocarcinoma.
AB  - Altering redox homeostasis provides distinctive therapeutic opportunities for the
      treatment of pancreatic cancer. Quinazolinediones (QDs) are novel redox
      modulators that we previously showed to induce potent growth inhibition in
      pancreatic ductal adenocarcinoma (PDAC) cell lines. Our lead optimization
      campaign yielded QD325 as the most potent redox modulator candidate inducing
      substantial reactive oxygen species (ROS) in PDAC cells. Nascent RNA sequencing
      following treatments with the QD compounds revealed induction of stress responses
      in nucleus, endoplasmic reticulum, and mitochondria of pancreatic cancer cells.
      Furthermore, the QD compounds induced Nrf2-mediated oxidative stress and unfolded
      protein responses as demonstrated by dose-dependent increases in RNA synthesis of
      representative genes such as NQO1, HMOX1, DDIT3, and HSPA5. At higher
      concentrations, the QDs blocked mitochondrial function by inhibiting mtDNA
      transcription and downregulating the mtDNA-encoded OXPHOS enzymes. Importantly,
      treatments with QD325 were well tolerated in vivo and significantly delayed tumor
      growth in mice. Our study supports the development of QD325 as a new therapeutic
      in the treatment of PDAC.

PMID- 29328655
TI  - Identification of Novel Coumestan Derivatives as Polyketide Synthase 13
      Inhibitors against Mycobacterium tuberculosis.
AB  - Inhibition of the mycolic acid pathway has proven a viable strategy in
      antitubercular drug discovery. The AccA3/AccD4/FadD32/Pks13 complex of
      Mycobacterium tuberculosis constitutes an essential biosynthetic mechanism for
      mycolic acids. Small molecules targeting the thioesterase domain of Pks13 have
      been reported, including a benzofuran-based compound whose X-ray cocrystal
      structure has been very recently solved. Its initial inactivity in a serum
      inhibition titration (SIT) assay led us to further probe other structurally
      related benzofurans with the aim to improve their potency and bioavailability.
      Herein, we report our preliminary structure-activity relationship studies around
      this scaffold, highlighting a natural product-inspired cyclization strategy to
      form coumestans that are shown to be active in SIT. Whole genome deep sequencing
      of the coumestan-resistant mutants confirmed a single nucleotide polymorphism in
      the pks13 gene responsible for the resistance phenotype, demonstrating the
      druggability of this target for the development of new antitubercular agents.

PMID- 29328657
TI  - Molecular Mechanism of Protein Unfolding under Shear: A Lattice Boltzmann
      Molecular Dynamics Study.
AB  - Proteins are marginally stable soft-matter entities that can be disrupted using a
      variety of perturbative stresses, including thermal, chemical, or mechanical
      ones. Fluid under extreme flow conditions is a possible route to probe the
      weakness of biomolecules and collect information on the molecular cohesive
      interactions that secure their stability. Moreover, in many cases, physiological
      flow triggers the functional response of specialized proteins as occurring in
      blood coagulation or cell adhesion. We deploy the Lattice Boltzmann molecular
      dynamics technique based on the coarse-grained model for protein OPEP to study
      the mechanism of protein unfolding under Couette flow. Our simulations provide a
      clear view of how structural elements of the proteins are affected by shear, and
      for the simple study case, the beta-hairpin, we exploited the analogy to pulling
      experiments to quantify the mechanical forces acting on the protein under shear.

PMID- 29328658
TI  - Modeling Net Land Occupation of Hydropower Reservoirs in Norway for Use in Life
      Cycle Assessment.
AB  - Increasing hydropower electricity production constitutes a unique opportunity to
      mitigate climate change impacts. However, hydropower electricity production also
      impacts aquatic and terrestrial biodiversity through freshwater habitat
      alteration, water quality degradation, and land use and land use change (LULUC).
      Today, no operational model exists that covers any of these cause-effect pathways
      within life cycle assessment (LCA). This paper contributes to the assessment of
      LULUC impacts of hydropower electricity production in Norway in LCA. We
      quantified the inundated land area associated with 107 hydropower reservoirs with
      remote sensing data and related it to yearly electricity production. Therewith,
      we calculated an average net land occupation of 0.027 m2.yr/kWh of Norwegian
      storage hydropower plants for the life cycle inventory. Further, we calculated an
      adjusted average land occupation of 0.007 m2.yr/kWh, accounting for an
      underestimation of water area in the performed maximum likelihood classification.
      The calculated land occupation values are the basis to support the development of
      methods for assessing the land occupation impacts of hydropower on biodiversity
      in LCA at a damage level.

PMID- 29328659
TI  - Syntheses of (-)-Tripterifordin and (-)-Neotripterifordin from Stevioside.
AB  - We report short syntheses of (-)-tripterifordin and (-)-neotripterifordin, potent
      inhibitors of HIV replication, from stevioside, a natural sweetener used
      worldwide. The key transformations are reduction at C13 through the formation of
      a tertiary chloride and subsequent three-step lactonization including a selective
      iodination at C20 by the photoreaction of the C19-alcohol. The title compounds
      were reliably obtained from stevioside in 9 and 11 steps (with 5-7 isolation
      steps), respectively. Additionally, the related lactone-containing ent-kaurenes,
      doianoterpenes A and B, and two more natural products were synthesized.

PMID- 29328660
TI  - X-ray Structures of Target-Ligand Complexes Containing Compounds with Assay
      Interference Potential.
AB  - Pan assay interference compounds (PAINS) have become a paradigm for compound
      classes that might cause artifacts in biological assays. PAINS-defining
      substructures are typically contained in larger compounds. We have systematically
      examined X-ray structures of protein-ligand complexes for compounds containing
      PAINS motifs. In 2874 X-ray structures, 1107 unique ligands with PAINS
      substructures belonging to 70 different classes were identified. PAINS most
      frequently detected in crystallographic ligands included a number of prominent
      candidates such as quinones, catechols, or Mannich bases. However, on the basis
      of X-ray data, the presence of specific ligand-target interactions and reactivity
      under assay conditions were not mutually exclusive. In some instances, reactivity
      of ligands was likely responsible for complex formation. Different categories of
      PAINS-containing ligands were distinguished, which aided in the interpretation of
      specific interactions versus potential assay artifacts. Careful consideration of
      structural data adds another dimension to the analysis of interference compounds.

PMID- 29328661
TI  - Investigation of Drug-Excipient Interactions in Biclotymol Amorphous Solid
      Dispersions.
AB  - The effect of low molecular weight excipients on drug-excipient interactions,
      molecular mobility, and propensity to recrystallization of an amorphous active
      pharmaceutical ingredient is investigated. Two structurally related excipients
      (alpha-pentaacetylglucose and beta-pentaacetylglucose), five different
      drug:excipient ratios (1:5, 1:2, 1:1, 2:1, and 5:1, w/w), and three different
      solid state characterization tools (differential scanning calorimetry, X-ray
      powder diffraction, and dielectric relaxation spectroscopy) were selected for the
      present research. Our investigation has shown that the excipient concentration
      and its molecular structure reveal quasi-identical molecular dynamic behavior of
      solid dispersions above and below the glass transition temperature. Across to
      complementary quantum mechanical simulations, we point out a clear indication of
      a strong interaction between biclotymol and the acetylated saccharides. Moreover,
      the thermodynamic study on these amorphous solid dispersions highlighted a
      stabilizing effect of alpha-pentaacetylglucose regardless of its quantity while
      an excessive concentration of beta-pentaacetylglucose revealed a poor
      crystallization inhibition. Finally, through long-term stability studies, we also
      showed the limiting excipient concentration needed to stabilize our amorphous
      API. Herewith, the developed procedure in this paper appears to be a promising
      tool for solid-state characterization of complex pharmaceutical formulations.

PMID- 29328662
TI  - Spin-Orbit Torques in NbSe2/Permalloy Bilayers.
AB  - We present measurements of current-induced spin-orbit torques generated by NbSe2,
      a fully metallic transition-metal dichalcogenide material, made using the spin
      torque ferromagnetic resonance (ST-FMR) technique with NbSe2/Permalloy bilayers.
      In addition to the out-of-plane Oersted torque expected from current flow in the
      metallic NbSe2 layer, we also observe an in-plane antidamping torque with torque
      conductivity sigmaS ~ 103 (h/2e)(Omegam)-1 and indications of a weak field-like
      contribution to the out-of-plane torque oriented opposite to the Oersted torque.
      Furthermore, in some samples we also measure an in-plane field-like torque with
      the form m * z, where m is the Permalloy magnetization direction and z is
      perpendicular to the sample plane. The size of this component varies strongly
      between samples and is not correlated with the NbSe2 thickness. A torque of this
      form is not allowed by the bulk symmetries of NbSe2 but is consistent with
      symmetry breaking by a uniaxial strain that might result during device
      fabrication.

PMID- 29328664
TI  - Aconicarmisulfonine A, a Sulfonated C20-Diterpenoid Alkaloid from the Lateral
      Roots of Aconitum carmichaelii.
AB  - A novel sulfonated C20-diterpenoid alkaloid with an unprecedented carbon skeleton
      and significant analgesic activity (46.7% inhibition at 0.1 mg/kg, i.p.), named
      aconicarmisulfonine A (1), was isolated from an aqueous extract of the lateral
      roots of Aconitum carmichaelii. Its structure was determined by comprehensive
      analysis of spectroscopic data, especially by 2D NMR spectroscopic data combined
      with ECD calculation and single-crystal X-ray diffraction. The plausible
      biosynthetic pathways of compound 1 are also discussed.

PMID- 29328665
TI  - Coalescence Dynamics of Mobile and Immobile Fluid Interfaces.
AB  - Coalescence dynamics between deformable bubbles and droplets can be dramatically
      affected by the mobility of the interfaces with fully tangentially mobile bubble
      liquid or droplet-liquid interfaces expected to accelerate the coalescence by
      orders of magnitude. However, there is a lack of systematic experimental
      investigations that quantify this effect. By using high speed camera imaging we
      examine the free rise and coalescence of small air-bubbles (100 to 1300 MUm in
      diameter) with a liquid interface. A perfluorocarbon liquid, PP11, is used as a
      model liquid to investigate coalescence dynamics between fully mobile and
      immobile deformable interfaces. The mobility of the bubble surface was determined
      by measuring the terminal rise velocity of small bubbles rising at Reynolds
      numbers, Re, less than 0.1 and the mobility of free PP11 surface by measuring the
      deceleration kinetics of the small bubble toward the interface. Induction or film
      drainage times of a bubble at the mobile PP11-air surface were found to be more
      than 2 orders of magnitude shorter compared to the case of bubble and an immobile
      PP11-water interface. A theoretical model is used to illustrate the effect of
      hydrodynamics and interfacial mobility on the induction time or film drainage
      time. The results of this study are expected to stimulate the development of a
      comprehensive theoretical model for coalescence dynamics between two fully or
      partially mobile fluid interfaces.

PMID- 29328663
TI  - Decarboxylative Annulation of alpha-Amino Acids with beta-Ketoaldehydes.
AB  - Indolizidine and quinolizidine derivatives are readily assembled from l-proline
      or (+/-)-pipecolic acid and beta-ketoaldehydes via a decarboxylative annulation
      process. These reactions are promoted by acetic acid and involve azomethine
      ylides as reactive intermediates.

PMID- 29328666
TI  - Directing Group Participated Benzylic C(sp3)-H/C(sp2)-H Cross-Dehydrogenative
      Coupling (CDC): Synthesis of Azapolycycles.
AB  - An efficient method to construct azapolycycles via directing group participated
      benzylic C(sp3)-H/C(sp2)-H cross-dehydrogenative coupling reactions is described.
      The reaction proceeded through a palladium catalyzed C(sp3)-H activation followed
      by coupling with a C(sp2)-H bond of quinoline to afford the azapolycyclic
      compounds. The reaction works with a broad substrate scope affording the products
      in moderate to good yields with excellent diastereoselectivities. Control
      experiments further supported the proposed mechanism.

PMID- 29328667
TI  - Enhancing Reactivity and Site-Selectivity in Hydrogen Atom Transfer from Amino
      Acid C-H Bonds via Deprotonation.
AB  - A kinetic study on the reactions of the cumyloxyl radical (CumO*) with N-Boc
      protected amino acids in the presence of the strong organic base DBU has been
      carried out. CO2H deprotonation increases the electron density at the alpha-C-H
      bonds activating these bonds toward HAT to the electrophilic CumO* strongly
      influencing the intramolecular selectivity. The implications of these results are
      discussed in the framework of HAT-based aliphatic C-H bond functionalization of
      amino acids and peptides.

PMID- 29328668
TI  - Bis(dinitrogen)cobalt(-1) Complexes with NHC Ligation: Synthesis,
      Characterization, and Their Dinitrogen Functionalization Reactions Affording Side
      on Bound Diazene Complexes.
AB  - Late-transition-metal-based catalysts are widely used in N2 fixation reactions,
      but the reactivity of late-transition-metal N2 complexes, besides iron N2
      complexes, has remained poorly understood as their N2 complexes were thought to
      be labile and hard to functionalize. By employing a monodentate N-heterocyclic
      carbene (NHC), 1,3-dicyclohexylimidazol-2-ylidene (ICy) as ligand, the cobalt(0)-
      and cobalt(-1)-N2 complexes, [(ICy)3Co(N2)] (1) and [(ICy)2Co(N2)2M]n (M = K, 2a;
      Rb, 2b; Cs, 2c), respectively, were synthesized from the stepwise reduction of
      (ICy)3CoCl by the corresponding alkaline metals under a N2 atmosphere. Complexes
      2a-c in their solid states adopt polymeric structures. The N-N distances
      (1.145(6)-1.162(5) A) and small N-N infrared stretchings (ca. 1800 and 1900 cm-1)
      suggest the strong N2 activation of the end-on N2 ligands in 2a-c. One electron
      oxidation of 1 by [Cp2Fe][BF4] gave the cobalt(I) complex devoid of N2 ligand
      [(ICy)3Co][BF4] (3). The bis(dinitrogen)cobalt(-1) complexes 2a-c undergo
      protonation reaction with triflic acid to give N2H4 in 24-30% yields (relative to
      cobalt). Complexes 2a-c could also react with silyl halides to afford diazene
      complexes [(ICy)2Co(eta2-R3SiNNSiR3)] (R = Me, 6a; Et, 6b) that are the first
      diazene complexes of late transition metals prepared from N2 functionalization.
      Characterization data, in combination with calculation results, suggest the
      electronic structures of the diazene complexes as low-spin cobalt(II) complexes
      containing dianionic ligand [eta2-R3SiNNSiR3]2-. Complexes 1, 2a-c, 6a, 6b, and
      (ICy)2CoCl2 proved to be effective catalysts for the reductive silylation of N2
      to afford N(SiMe3)3. These NHC-cobalt catalysts display comparable turnover
      numbers (ca. 120) that exceed the reported 3d metal catalysts. The fine
      performance of the NHC-cobalt complexes in the stoichiometric and catalytic N2
      functionalization reactions points out the utility of low-valent low-coordinate
      group 9 metal species for N2 fixation.

PMID- 29328669
TI  - Urinary Methyleugenol-deoxyadenosine Adduct as a Potential Biomarker of
      Methyleugenol Exposure in Rats.
AB  - Methyleugenol (ME), a natural ingredient of several herbs and spices used in the
      human diet, is hepatocarcinogenic in rodents. Following metabolic activation to
      the reactive carbocation intermediate, ME can bind covalently to DNA, which is
      directly associated with its carcinogenicity. In this work, a non-invasive
      approach to determine ME exposure was established by monitoring the urinary N6
      (methylisoeugenol-3'-yl)-2'-deoxyadenosine (ME-dA) adduct. The developed method
      entails liquid-liquid extraction enrichment of urinary ME-dA, incorporation of
      deuterated ME-dA as an internal standard, and analysis by liquid chromatography
      coupled tandem mass spectrometry. Male rats (10-12 weeks, 180-200 g) were treated
      (p.o.) with ME, and ME-dA was excreted in urine in a dose- and time-dependent
      manner. The non-invasive approach enabled us to successfully determine exposure
      to ME-containing herbs and spices. These results suggest that ME-dA can
      potentially serve as an effective biomarker of ME exposure in rats. It is
      expected that the developed approach of detecting urinary ME-dA will facilitate
      the investigation of ME carcinogenesis.

PMID- 29328670
TI  - Surface Oxidation of Graphene Oxide Determines Membrane Damage, Lipid
      Peroxidation, and Cytotoxicity in Macrophages in a Pulmonary Toxicity Model.
AB  - While two-dimensional graphene oxide (GO) is used increasingly in biomedical
      applications, there is uncertainty on how specific physicochemical properties
      relate to biocompatibility in mammalian systems. Although properties such as
      lateral size and the colloidal properties of the nanosheets are important, the
      specific material properties that we address here is the oxidation state and
      reactive surface groups on the planar surface. In this study, we used a GO
      library, comprising pristine, reduced (rGO), and hydrated GO (hGO), in which
      quantitative assessment of the hydroxyl, carboxyl, epoxy, and carbon radical
      contents was used to study the impact on epithelial cells and macrophages, as
      well as in the murine lung. Strikingly, we observed that hGO, which exhibits the
      highest carbon radical density, was responsible for the generation of cell death
      in THP-1 and BEAS-2B cells as a consequence of lipid peroxidation of the surface
      membrane, membrane lysis, and cell death. In contrast, pristine GO had lesser
      effects, while rGO showed extensive cellular uptake with minimal effects on
      viability. In order to see how these in vitro effects relate to adverse outcomes
      in the lung, mice were exposed to GOs by oropharyngeal aspiration. Animal
      sacrifice after 40 h demonstrated that hGO was more prone than other materials to
      generate acute lung inflammation, accompanied by the highest lipid peroxidation
      in alveolar macrophages, cytokine production (LIX, MCP-1), and LDH release in
      bronchoalveolar lavage fluid. Pristine GO showed less toxicity, whereas rGO had
      minimal effects. We demonstrate that the surface oxidation state and carbon
      radical content play major roles in the induction of toxicity by GO in mammalian
      cells and the lung.

PMID- 29328671
TI  - Dimethylcalcium.
AB  - The salt metathesis reaction between homoleptic calcium bis(trimethylsilyl)amide
      [Ca{N(SiMe3)2}2]2 and "halide-free" methyllithium allowed for the isolation of X
      ray-amorphous dimethylcalcium [CaMe2]n in good yields and purities. The formation
      of [CaMe2]n was proven by microanalysis and NMR/FTIR spectroscopic methods as
      well as a series of derivatization reactions. Despite slowly decomposing thf,
      [CaMe2]n could be crystallized from chilled thf solutions as the heptametallic
      adduct [(thf)10Ca7Me14]. Reaction of [CaMe2]n with CaI2 in thf led to the dimeric
      complex [(thf)3Ca(Me)(I)]2, whereas in tetrahydropyran (thp) the trinuclear
      complex [(thp)5Ca3(Me)5(I)] was obtained, both representing the first
      crystallographically characterized heavy-Grignard compounds with methyl groups as
      the hydrocarbyl ligand. While protonolysis of [CaMe2]n with the superbulky
      proligand HTptBu,Me in nonpolar solvents gave homoleptic (TptBu,Me)2Ca, reaction
      in donor solvents (thf, thp) afforded the monomeric complexes
      [(TptBu,Me)Ca(Me)(thf)] and [(TptBu,Me)Ca(Me)(thp)], which are the first examples
      bearing terminal Ca-CH3 functionalities. Grignard-type nucleophilic methyl-group
      transfer to hexamethylacetone gave access to the dimeric alkoxide complexes
      [(thf)Ca(OCtBu2Me)2]2 and [(tBu2CO)Ca(MU2-OCtBu2Me)3Ca(OCtBu2Me)]. Finally,
      addition of the Lewis acid GaMe3 to [CaMe2]n led to the corresponding
      tetramethylgallate compound [Ca(GaMe4)2]n.

PMID- 29328672
TI  - Three-Dimensional Printing Hollow Polymer Template-Mediated Graphene Lattices
      with Tailorable Architectures and Multifunctional Properties.
AB  - It is a significant challenge to concurrently achieve scalable fabrication of
      graphene aerogels with three-dimensional (3D) tailorable architectures (e.g.,
      lattice structure) and controllable manipulation of microstructures on the
      multiscale. Herein, we highlight 3D graphene lattices (GLs) with complex
      engineering architectures that were delicately designed and manufactured via 3D
      stereolithography printed hollow polymer template-mediated hydrothermal process
      coupled with freeze-drying strategies. The resulting GLs with overhang beams and
      columns show a 3D geometric configuration with hollow-carved features at the
      macroscale, while the construction elements of graphene cellular on the
      microscale exhibit a well-ordered and honeycomb-like microstructure with high
      porosity. These GLs demonstrate multifunctional properties with robust structure,
      high electrical conductivity, low thermal conductivity, and superior absorption
      capacitance of organic solvents. Moreover, the GLs were utilized as a subtle
      sensor for the fast detection of chemical agents. Aforementioned superior
      properties of GLs confirm that the combination of 3D tailorable manipulation and
      self-organization design of structures on the multiscale is an effective strategy
      for the scalable fabrication of advanced multifunctional graphene monoliths,
      suggesting their promising applications as chemical detection sensors,
      environmental remediation absorbers, conductive electrodes, and engineering
      metamaterials.

PMID- 29328673
TI  - Fluorescent Proteins Detect Host Structural Rearrangements via Electrostatic
      Mechanism.
AB  - The rational design of genetically encoded fluorescent biosensors, which can
      detect rearrangements of target proteins via interdomain allostery, is hindered
      by the absence of mechanistic understanding of the underlying photophysics. Here,
      we focus on the modulation of fluorescence by mechanical perturbation in a
      popular biological probe: enhanced Green Fluorescent Protein (eGFP). Using a
      combination of molecular dynamics (MD) simulations and quantum chemistry, and a
      set of physically motivated assumptions, we construct a map of fluorescence
      quantum yield as a function of a 2D electric field imposed by the protein
      environment on the fluorophore. This map is transferable between Tsien's Class 2
      GFP's, and it allows one to estimate the shifts in fluorescence intensity due to
      mechanical perturbations directly from MD simulations. We use it in combination
      with steered MD simulations to put forward a hypothesis for the mechanism of a
      genetically encoded voltage probe (ArcLight) whose mechanism is currently under
      debate.

PMID- 29328674
TI  - New Insights on Ecosystem Mercury Cycling Revealed by Stable Isotopes of Mercury
      in Water Flowing from a Headwater Peatland Catchment.
AB  - Stable isotope compositions of mercury (Hg) were measured in the outlet stream
      and in soil cores at different landscape positions in a 9.7-ha boreal upland
      peatland catchment. An acidic permanganate/persulfate digestion procedure was
      validated for water samples with high dissolved organic matter (DOM)
      concentrations through Hg spike addition analysis. We report a relatively large
      variation in mass-dependent fractionation (delta202Hg; from -2.12 to -1.320/00)
      and a smaller, but significant, variation of mass-independent fractionation
      (Delta199Hg; from -0.35 to -0.120/00) during two years of sampling with
      streamflow varying from 0.003 to 7.8 L s-1. Large variations in delta202Hg
      occurred only during low streamflow (<0.6 L s-1), which suggest that under high
      streamflow conditions a peatland lagg zone between the bog (3.0 ha) and uplands
      (6.7 ha) becomes the dominant source of Hg in downstream waters. Further, a
      binary mixing model showed that except for the spring snowmelt period, Hg in
      streamwater from the catchment was mainly derived from dry deposition of gaseous
      elemental Hg (73-95%). This study demonstrates the usefulness of Hg isotopes for
      tracing sources of Hg deposition, which can lead to a better understanding of the
      biogeochemical cycling and hydrological transport of Hg in headwater catchments.

PMID- 29328675
TI  - Design, Synthesis, and Evaluation of N- and C-Terminal Protein Bioconjugates as G
      Protein-Coupled Receptor Agonists.
AB  - A G protein-coupled receptor (GPCR) agonist protein, thaumatin, was site
      specifically conjugated at the N- or C-terminus with a fluorophore for
      visualization of GPCR:agonist interactions. The N-terminus was specifically
      conjugated using a synthetic 2-pyridinecarboxyaldehyde reagent. The interaction
      profiles observed for N- and C-terminal conjugates were varied; N-terminal
      conjugates interacted very weakly with the GPCR of interest, whereas C-terminal
      conjugates bound to the receptor. These chemical biology tools allow interactions
      of therapeutic proteins:GPCR to be monitored and visualized. The methodology used
      for site-specific bioconjugation represents an advance in application of 2
      pyridinecarboxyaldehydes for N-terminal specific bioconjugations.

PMID- 29328676
TI  - Stabilizing Leaf and Branch Compost Cutinase (LCC) with Glycosylation: Mechanism
      and Effect on PET Hydrolysis.
AB  - Cutinases are polyester hydrolases that show a remarkable capability to hydrolyze
      polyethylene terephthalate (PET) to its monomeric units. This revelation has
      stimulated research aimed at developing sustainable and green cutinase-catalyzed
      PET recycling methods. Leaf and branch compost cutinase (LCC) is particularly
      suited toward these ends given its relatively high PET hydrolysis activity and
      thermostability. Any practical enzymatic PET recycling application will require
      that the protein have kinetic stability at or above the PET glass transition
      temperature (Tg, i.e., 70  degrees C). This paper elucidates the thermodynamics
      and kinetics of LCC conformational and colloidal stability. Aggregation emerged
      as a major contributor that reduces LCC kinetic stability. In its native state,
      LCC is prone to aggregation owing to electrostatic interactions. Further, with
      increasing temperature, perturbation of LCC's tertiary structure and
      corresponding exposure of hydrophobic domains leads to rapid aggregation.
      Glycosylation was employed in an attempt to impede LCC aggregation. Owing to the
      presence of three putative N-glycosylation sites, expression of native LCC in
      Pichia pastoris resulted in the production of glycosylated LCC (LCC-G). LCC-G
      showed improved stability to native state aggregation while increasing the
      temperature for thermal induced aggregation by 10  degrees C. Furthermore,
      stabilization against thermal aggregation resulted in improved catalytic PET
      hydrolysis both at its optimum temperature and concentration.

PMID- 29328677
TI  - Metabolic Analysis Reveals Altered Long-Chain Fatty Acid Metabolism in the Host
      by Huanglongbing Disease.
AB  - Candidatus Liberibacter asiaticus (CLas) is the presumed causal agent of
      Huanglongbing, one of the most destructive diseases in citrus. However, the lipid
      metabolism component of host response to this pathogen has not been investigated
      well. Here, metabolic profiling of a variety of long-chain fatty acids and their
      oxidation products was first performed to elucidate altered host metabolic
      responses of disease. Fatty acid signals were found to decrease obviously in
      response to disease regardless of cultivar. Several lipid oxidation products
      strongly correlated with those fatty acids were also consistently reduced in the
      diseased group. Using a series of statistical methods and metabolic pathway
      mapping, we found significant markers contributing to the pathological symptoms
      and identified their internal relationships and metabolic network. Our findings
      suggest that the infection of CLas may cause the altered metabolism of long-chain
      fatty acids, possibly leading to manipulation of the host's defense derived from
      fatty acids.

PMID- 29328678
TI  - Colossal Anisotropy of the Dynamic Magnetic Susceptibility in Low-Dimensional
      Nanocube Assemblies.
AB  - One of the ultimate goals of nanocrystal self-assembly is to transform nanoscale
      building blocks into a material that displays enhanced properties relative to the
      sum of its parts. Herein, we demonstrate that 1D needle-shaped assemblies
      composed of Fe3-deltaO4 nanocubes display a significant augmentation of the
      magnetic susceptibility and dissipation as compared to 0D and 2D systems. The
      performance of the nanocube needles is highlighted by a colossal anisotropy
      factor defined as the ratio of the parallel to the perpendicular magnetization
      components. We show that the origin of this effect cannot be ascribed to shape
      anisotropy in its classical sense; as such, it has no analogy in bulk magnetic
      materials. The temperature-dependent anisotropy factors of the in- and out-of
      phase components of the magnetization have an extremely strong particle size
      dependence and reach values of 80 and 2500, respectively, for the largest
      nanocubes in this study. Aided by simulations, we ascribe the anisotropy of the
      magnetic susceptibility, and its strong particle-size dependence to a synergistic
      coupling between the dipolar interaction field and a net anisotropy field
      resulting from a partial texture in the 1D nanocube needles.

PMID- 29328679
TI  - Effect of End-Grafted Polymer Conformation on Protein Resistance.
AB  - Monte Carlo simulation combined with an experimental method was used to
      investigate the effect of the conformational structure of polymer brushes on
      their protein resistance. The end-grafted polymers with two conformational
      structures, i.e., linear and looped, were considered. Protein adsorption
      behaviors on the surfaces grafted with either linear or looped polymers were
      investigated. Different chain lengths and grafting numbers of end-grafted
      polymers were employed in this simulation. The simulation results indicated that
      for long polymer brushes the conformational change from linear to looped
      generally improved their protein-resistant property for all of the grafting
      numbers investigated here, and a remarkable improvement in protein resistance can
      be achieved at a certain grafting number. Moreover, the simulations revealed that
      the smoothness of the surface and the formation of a dense impenetrable layer are
      the two significant characteristics of the looped polymer brush in resisting
      protein adsorption. Meanwhile, experiment results also showed that for a given
      chain length and grafting number the protein-resistant property of the looped
      polymer brush was superior to that of the surface grafted with linear polymers,
      which is quite consistent with the simulation results. These results further
      elucidated the difference in the protein-resistant property between the linear
      and looped polymer brushes, which provided useful information for preparing
      excellent antifouling materials in future experiments.

PMID- 29328680
TI  - Insomnia and motor vehicle accident-related injuries, active component, U.S.
      Armed Forces, 2007-2016.
AB  - Insomnia is the most common sleep disorder in adults, and its incidence is
      increasing in the U.S. Armed Forces. A potential consequence of insomnia
      (including medications used to treat it) is increased risk of motor vehicle
      accidents (MVAs), which cause significant morbidity and mortality in service
      members. To examine the relationship between insomnia and MVA-related injuries in
      the U.S. Armed Forces, this retrospective cohort study compared incidence rates
      of MVA-related injuries from 2007 through 2016 between service members with
      diagnosed insomnia and an unexposed cohort. After adjustment for multiple
      covariates, service members with insomnia had more than double the rate of MVA
      related injuries, compared to service members without insomnia (adjusted
      incidence rate ratio: 2.08; 95% CI: 1.95-2.22). A subanalysis of service members
      with insomnia during 2014-2016 found no difference in risk of MVA-related injury
      based on days' supply of sleep aid medications prescribed in 365 days following
      insomnia diagnosis. Insomnia is an important potential risk factor for MVAs in
      the military. Sleep health should be a component of MVA prevention efforts.

PMID- 29328682
TI  - Brief report: Prevalence of hepatitis B and C virus infections in U.S. Air Force
      basic military trainees who donated blood, 2013-2016.
AB  - Hepatitis B virus (HBV) and hepatitis C virus (HCV) can cause significant
      morbidity in military service members. Prevalences of HBV and HCV infections
      among military recruits accessioning into the U.S. Air Force have not previously
      been described. The Joint Base San Antonio-Lackland Blood Donor Center was
      queried for the results of HBV and HCV screening tests among all basic military
      trainees who donated blood between 25 November 2013 and 16 April 2016. Other
      active and reserve component members were excluded. The estimated prevalences of
      HBV and HCV infections among recruit blood donors were 0.0098% and 0.007%,
      respectively. This study suggests that the overall estimated prevalence of HBV
      and HCV infection is much lower among U.S. Air Force basic trainees, compared to
      other active and reserve component members and U.S. civilian populations. HBV and
      HCV viral infections can have a negative impact on mission readiness and
      individual deployment status, and have significant costs for the military.
      Additional studies are needed to determine cost effectiveness of screening for
      viral hepatitis among military populations.

PMID- 29328681
TI  - Seizures among active component service members, U.S. Armed Forces,2007-2016.
AB  - Traumatic brain injury (TBI) is a known risk factor for seizures. Evidence also
      shows that post-traumatic stress disorder (PTSD) is associated with seizures, but
      the relationship in the absence of TBI remains unclear. This retrospective study
      spanning 2007-2016 separately quantifies the rates of seizures diagnosed among
      deployed and non-deployed active component military service members to understand
      the factors associated with seizures and whether they differ in deployed
      settings. Higher rates of seizures were associated with service members who were
      in the Army or Marine Corps; female; black; younger; lower enlisted; in a combat
      specific, armor/motor transport, or healthcare occupation; and who had no more
      than one previous deployment. These associations were similar among both deployed
      and non-deployed service members. Either a TBI or recent PTSD diagnosis was
      associated with a 3- to 4-fold increased seizure rate. For service members who
      had received both diagnoses, seizure rates among the deployed and the non
      deployed were two and three times the rates among those with only one of those
      diagnoses, respectively. If the current results are supported by future
      investigations, there may be implications for both clinical care and military
      policy.

PMID- 29328683
TI  - Fatigue and related comorbidities, active component, U.S. Armed Forces, 2007
      2016.
AB  - Fatigue is a common complaint in the civilian population and may be a presenting
      symptom of more serious physical and mental disorders. Data from the Defense
      Medical Surveillance System (DMSS) were utilized to characterize the incidence
      and burden of fatigue in active component military members from 1 January 2007
      through 31 December 2016. A subanalysis of 3 years within this surveillance
      period (2012-2014) was also conducted to assess the burden of comorbidities
      related to incident fatigue and the strength of the association between fatigue
      and selected comorbidities. The study identified 211,213 incident cases of
      fatigue with an overall incidence rate of 18.1 per 1,000 person-years between
      2007 and 2016. Mental disorders and musculoskeletal disease accounted for about
      35% of all medical encounters and about 40% of all hospital days within a year
      for those diagnosed with fatigue in 2013. The adjusted odds ratio for fatigue was
      highest in those with male hypogonadism, thyroid disorder, and sleep problems.
      These results show that fatigue is a common diagnosis with high incidence and
      burden among active component U.S. military. By focusing on the conditions that
      frequently occur and are highly associated with fatigue, more rapid diagnosis and
      treatment of the underlying cause of service member fatigue is possible.

PMID- 29328684
TI  - Hydrodynamic Signatures of Stationary Marangoni-Driven Surfactant Transport.
AB  - We experimentally study steady Marangoni-driven surfactant transport on the
      interface of a deep water layer. Using hydrodynamic measurements, and without
      using any knowledge of the surfactant physicochemical properties, we show that
      sodium dodecyl sulphate and Tergitol 15-S-9 introduced in low concentrations
      result in a flow driven by adsorbed surfactant. At higher surfactant
      concentration, the flow is dominated by the dissolved surfactant. Using camphoric
      acid, whose properties are a priori unknown, we demonstrate this method's
      efficacy by showing its spreading is adsorption dominated.

PMID- 29328685
TI  - Tunable Intrinsic Plasmons due to Band Inversion in Topological Materials.
AB  - Band inversion has led to rich physical effects in both topological insulators
      and topological semimetals. It has been found that the inverted band structure
      with the Mexican-hat dispersion could enhance the interband correlation leading
      to a strong intrinsic plasmon excitation. Its frequency ranges from several meV
      to tens of meV and can be effectively tuned by the external fields. The electron
      hole asymmetric term splits the peak of the plasmon excitation into double peaks.
      The fate and properties of this plasmon excitation can also act as a probe to
      characterize the topological phases even in lightly doped systems. We numerically
      demonstrate the impact of band inversion on plasmon excitations in magnetically
      doped thin films of three-dimensional strong topological insulators, V- or Cr
      doped (Bi,Sb)_{2}Te_{3}, which support the quantum anomalous Hall states. Our
      work thus sheds some new light on the potential applications of topological
      materials in plasmonics.

PMID- 29328686
TI  - Three-Dimensional Tracking of Interfacial Hopping Diffusion.
AB  - Theoretical predictions have suggested that molecular motion at interfaces-which
      influences processes including heterogeneous catalysis, (bio)chemical sensing,
      lubrication and adhesion, and nanomaterial self-assembly-may be dominated by
      hypothetical "hops" through the adjacent liquid phase, where a diffusing molecule
      readsorbs after a given hop according to a probabilistic "sticking coefficient."
      Here, we use three-dimensional (3D) single-molecule tracking to explicitly
      visualize this process for human serum albumin at solid-liquid interfaces that
      exert varying electrostatic interactions on the biomacromolecule. Following
      desorption from the interface, a molecule experiences multiple unproductive
      surface encounters before readsorption. An average of approximately seven surface
      collisions is required for the repulsive surfaces, decreasing to approximately
      two and a half for surfaces that are more attractive. The hops themselves are
      also influenced by long-range interactions, with increased electrostatic
      repulsion causing hops of longer duration and distance. These findings explicitly
      demonstrate that interfacial diffusion is dominated by biased 3D Brownian motion
      involving bulk-surface coupling and that it can be controlled by influencing
      short- and long-range adsorbate-surface interactions.

PMID- 29328687
TI  - Erratum: Ultrafine Entanglement Witnessing [Phys. Rev. Lett. 118, 110502 (2017)].
AB  - This corrects the article DOI: 10.1103/PhysRevLett.118.110502.

PMID- 29328688
TI  - Astrometric Search Method for Individually Resolvable Gravitational Wave Sources
      with Gaia.
AB  - Gravitational waves (GWs) cause the apparent position of distant stars to
      oscillate with a characteristic pattern on the sky. Astrometric measurements
      (e.g., those made by Gaia) provide a new way to search for GWs. The main
      difficulty facing such a search is the large size of the data set; Gaia observes
      more than one billion stars. In this Letter the problem of searching for GWs from
      individually resolvable supermassive black hole binaries using astrometry is
      addressed for the first time; it is demonstrated how the data set can be
      compressed by a factor of more than 10^{6}, with a loss of sensitivity of less
      than 1%. This technique was successfully used to recover artificially injected GW
      signals from mock Gaia data and to assess the GW sensitivity of Gaia. Throughout
      the Letter the complementarity of Gaia and pulsar timing searches for GWs is
      highlighted.

PMID- 29328689
TI  - High-Energy Limit of QCD beyond the Sudakov Approximation.
AB  - We study the high-energy fixed-angle Sudakov limit of the scattering amplitudes
      suppressed by the leading power of the quark mass in perturbative quantum
      chromodynamics. We prove the factorization and perform all-order resummation of
      the double-logarithmic radiative corrections which determine the asymptotic
      behavior of the amplitudes. In contrast to the Sudakov logarithms, the mass
      suppressed double-logarithmic corrections are induced by soft quark exchange. The
      structure of the corrections and the asymptotic behavior of the amplitudes in
      this case crucially depend on the color flow in a given process and are
      determined by the eikonal color charge nonconservation. We present explicit
      results for the Higgs boson production in gluon fusion mediated by a light-quark
      loop and for the leading power-suppressed contributions to the quark form
      factors, which reveal "magical" universality. Nontrivial relations between the
      asymptotic behavior of different amplitudes and the amplitudes in different gauge
      theories are found.

PMID- 29328691
TI  - Landau Phonon-Roton Theory Revisited for Superfluid ^{4}He and Fermi Gases.
AB  - Liquid helium and spin-1/2 cold-atom Fermi gases both exhibit in their superfluid
      phase two distinct types of excitations, gapless phonons and gapped rotons or
      fermionic pair-breaking excitations. In the long wavelength limit, revising and
      extending the theory of Landau and Khalatnikov initially developed for helium
      [Zh. Exp. Teor. Fiz. 19, 637 (1949)], we obtain universal expressions for three-
      and four-body couplings among these two types of excitations. We calculate the
      corresponding phonon damping rates at low temperature and compare them to those
      of a pure phononic origin in high-pressure liquid helium and in strongly
      interacting Fermi gases, paving the way to experimental observations.

PMID- 29328690
TI  - One-Parameter Scaling Theory for DNA Extension in a Nanochannel.
AB  - Experiments measuring DNA extension in nanochannels are at odds with even the
      most basic predictions of current scaling arguments for the conformations of
      confined semiflexible polymers such as DNA. We show that a theory based on a
      weakly self-avoiding, one-dimensional "telegraph" process collapses experimental
      data and simulation results onto a single master curve throughout the
      experimentally relevant region of parameter space and explains the mechanisms at
      play.

PMID- 29328692
TI  - Role of the Pair Correlation Function in the Dynamical Transition Predicted by
      Mode Coupling Theory.
AB  - In a recent study, we have found that for a large number of systems the
      configurational entropy at the pair level S_{c2}, which is primarily determined
      by the pair correlation function, vanishes at the dynamical transition
      temperature T_{c}. Thus, it appears that the information of the transition
      temperature is embedded in the structure of the liquid. In order to investigate
      this, we describe the dynamics of the system at the mean field level and, using
      the concepts of the dynamical density functional theory, show that the dynamical
      transition temperature depends only on the pair correlation function. Thus, this
      theory is similar in spirit to the microscopic mode coupling theory (MCT).
      However, unlike microscopic MCT, which predicts a very high transition
      temperature, the present theory predicts a transition temperature that is similar
      to T_{c}. This implies that the information of the dynamical transition
      temperature is embedded in the pair correlation function.

PMID- 29328693
TI  - Coevolution Maintains Diversity in the Stochastic "Kill the Winner" Model.
AB  - The "kill the winner" hypothesis is an attempt to address the problem of
      diversity in biology. It argues that host-specific predators control the
      population of each prey, preventing a winner from emerging and thus maintaining
      the coexistence of all species in the system. We develop a stochastic model for
      the kill the winner paradigm and show that the stable coexistence state of the
      deterministic kill the winner model is destroyed by demographic stochasticity,
      through a cascade of extinction events. We formulate an individual-level
      stochastic model in which predator-prey coevolution promotes the high diversity
      of the ecosystem by generating a persistent population flux of species.

PMID- 29328694
TI  - Resilient Nodeless d-Wave Superconductivity in Monolayer FeSe.
AB  - Monolayer FeSe exhibits the highest transition temperature among the iron based
      superconductors and appears to be fully gapped, seemingly consistent with s-wave
      superconductivity. Here, we develop a theory for the superconductivity based on
      coupling to fluctuations of checkerboard magnetic order (which has the same
      translation symmetry as the lattice). The electronic states are described by a
      symmetry based k.p-like theory and naturally account for the states observed by
      angle resolved photoemission spectroscopy. We show that a prediction of this
      theory is that the resultant superconducting state is a fully gapped, nodeless, d
      wave state. This state, which would usually have nodes, stays nodeless because,
      as seen experimentally, the relevant spin-orbit coupling has an energy scale
      smaller than the superconducting gap.

PMID- 29328695
TI  - Color Memory: A Yang-Mills Analog of Gravitational Wave Memory.
AB  - A transient color flux across null infinity in classical Yang-Mills theory is
      considered. It is shown that a pair of test "quarks" initially in a color singlet
      generically acquire net color as a result of the flux. A nonlinear formula is
      derived for the relative color rotation of the quarks. For a weak color flux, the
      formula linearizes to the Fourier transform of the soft gluon theorem. This color
      memory effect is the Yang-Mills analog of the gravitational memory effect.

PMID- 29328696
TI  - Symmetry Preservation and Critical Fluctuations in a Pseudospin Crossover
      Perovskite LaCoO_{3}.
AB  - Spin-state crossover beyond a conventional ligand-field theory has been a
      fundamental issue in condensed matter physics. Here, we report microscopic
      observations of spin states and low-energy dynamics through orbital-resolved NMR
      spectroscopy in the prototype compound LaCoO_{3}. The ^{59}Co NMR spectrum shows
      the preserved crystal symmetry across the crossover, inconsistent with d orbital
      ordering due to the Jahn-Teller distortion. The orbital degeneracy results in a
      pseudospin (J[over ~]=1) excited state with an orbital moment observed as ^{59}Co
      hyperfine coupling tensors. We found that the population of the excited state
      evolves above the heart crossover temperature. The crossover involves critical
      spin-state fluctuations emerging under the magnetic field. These results suggest
      that the spin-state crossover can be mapped into a statistical problem, analogous
      to the supercritical liquid in liquid-gas transition.

PMID- 29328698
TI  - Emergence of Long-Ranged Stress Correlations at the Liquid to Glass Transition.
AB  - A theory for the nonlocal shear stress correlations in supercooled liquids is
      derived from first principles. It captures the crossover from viscous to elastic
      dynamics at an idealized liquid to glass transition and explains the emergence of
      long-ranged stress correlations in glass, as expected from classical continuum
      elasticity. The long-ranged stress correlations can be traced to the coupling of
      shear stress to transverse momentum, which is ignored in the classic Maxwell
      model. To rescue this widely used model, we suggest a generalization in terms of
      a single relaxation time tau for the fast degrees of freedom only. This
      generalized Maxwell model implies a divergent correlation length xi?tau as well
      as dynamic critical scaling and correctly accounts for the far-field stress
      correlations. It can be rephrased in terms of generalized hydrodynamic equations,
      which naturally couple stress and momentum and furthermore allow us to connect to
      fluidity and elastoplastic models.

PMID- 29328697
TI  - Sorting Photons by Radial Quantum Number.
AB  - The Laguerre-Gaussian (LG) modes constitute a complete basis set for representing
      the transverse structure of a paraxial photon field in free space. Earlier
      workers have shown how to construct a device for sorting a photon according to
      its azimuthal LG mode index, which describes the orbital angular momentum (OAM)
      carried by the field. In this paper we propose and demonstrate a mode sorter
      based on the fractional Fourier transform to efficiently decompose the optical
      field according to its radial profile. We experimentally characterize the
      performance of our implementation by separating individual radial modes as well
      as superposition states. The reported scheme can, in principle, achieve unit
      efficiency and thus can be suitable for applications that involve quantum states
      of light. This approach can be readily combined with existing OAM mode sorters to
      provide a complete characterization of the transverse profile of the optical
      field.

PMID- 29328699
TI  - Oscillations in Aggregation-Shattering Processes.
AB  - We observe never-ending oscillations in systems undergoing collision-controlled
      aggregation and shattering. Specifically, we investigate aggregation-shattering
      processes with aggregation kernels K_{i,j}=(i/j)^{a}+(j/i)^{a} and shattering
      kernels F_{i,j}=lambdaK_{i,j}, where i and j are cluster sizes, and parameter
      lambda quantifies the strength of shattering. When 0<=a<1/2, there are no
      oscillations, and the system monotonically approaches a steady state for all
      values of lambda; in this region, we obtain an analytical solution for the
      stationary cluster size distribution. Numerical solutions of the rate equations
      show that oscillations emerge in the 1/2<a<=1 range. When lambda is sufficiently
      large, oscillations decay and eventually disappear, while for
      lambda<lambda_{c}(a), oscillations apparently persist forever. Thus, never-ending
      oscillations can arise in closed aggregation-shattering processes without sinks
      and sources of particles.

PMID- 29328700
TI  - Magnetic Moment Orientation-Dependent Spin Dissipation in Antiferromagnets.
AB  - Spin interaction in antiferromagnetic materials is of central interest in the
      recently emerging antiferromagnetic spintronics. In this Letter, we explore the
      spin current interaction in antiferromagnetic FeMn by the spin pumping effect.
      Exchange biased FeNi/FeMn films, in which the Neel vector can be presumably
      controlled via the exchange spring effect, are employed to investigate the
      damping enhancement depending on the relative orientation between the Neel vector
      and the polarization of the pumped spin current. The correlation between the
      enhanced damping and the strength of the exchange bias suggests that the twisting
      of the Neel vector induces an additional spin dissipation, which verifies that
      the Slonczewski-type spin torque is effective even in antiferromagnetic
      materials.

PMID- 29328701
TI  - Spin-Orbit Coupling and Interband Transitions in the Optical Conductivity of
      Sr_{2}RhO_{4}.
AB  - The prototypical correlated metal Sr_{2}RhO_{4} was studied using optical and
      photoemission spectroscopy. At low energies and temperatures, the optical data
      reveal a complex, multicomponent response that on the surface points to an
      unconventional metallic state in this material. Via a comparison with
      photoemission, the anomalous optical response may be attributed to an
      unexpectedly strong interband transition near 180 meV between spin-orbit coupled
      bands that are nearly parallel along GammaX. This spin-orbit coupling effect is
      shown to occur in a number of related metallic ruthenates and explains the
      previously puzzling optical properties reported for these materials.

PMID- 29328702
TI  - Peeling Off Neutron Skins from Neutron-Rich Nuclei: Constraints on the Symmetry
      Energy from Neutron-Removal Cross Sections.
AB  - An experimentally constrained equation of state of neutron-rich matter is
      fundamental for the physics of nuclei and the astrophysics of neutron stars,
      mergers, core-collapse supernova explosions, and the synthesis of heavy elements.
      To this end, we investigate the potential of constraining the density dependence
      of the symmetry energy close to saturation density through measurements of
      neutron-removal cross sections in high-energy nuclear collisions of 0.4 to 1
      GeV/nucleon. We show that the sensitivity of the total neutron-removal cross
      section is high enough so that the required accuracy can be reached
      experimentally with the recent developments of new detection techniques. We
      quantify two crucial points to minimize the model dependence of the approach and
      to reach the required accuracy: the contribution to the cross section from
      inelastic scattering has to be measured separately in order to allow a direct
      comparison of experimental cross sections to theoretical cross sections based on
      density functional theory and eikonal theory. The accuracy of the reaction model
      should be investigated and quantified by the energy and target dependence of
      various nucleon-removal cross sections. Our calculations explore the dependence
      of neutron-removal cross sections on the neutron skin of medium-heavy neutron
      rich nuclei, and we demonstrate that the slope parameter L of the symmetry energy
      could be constrained down to +/-10  MeV by such a measurement, with a 2% accuracy
      of the measured and calculated cross sections.

PMID- 29328703
TI  - Asymptotic One-Point Functions in Gauge-String Duality with Defects.
AB  - We take the first step in extending the integrability approach to one-point
      functions in AdS/dCFT to higher loop orders. More precisely, we argue that the
      formula encoding all tree-level one-point functions of SU(2) operators in the
      defect version of N=4 supersymmetric Yang-Mills theory, dual to the D5-D3 probe
      brane system with flux, has a natural asymptotic generalization to higher loop
      orders. The asymptotic formula correctly encodes the information about the one
      loop correction to the one-point functions of nonprotected operators once dressed
      by a simple flux-dependent factor, as we demonstrate by an explicit computation
      involving a novel object denoted as an amputated matrix product state.
      Furthermore, when applied to the Berenstein-Maldacena-Nastase vacuum state, the
      asymptotic formula gives a result for the one-point function which in a certain
      double-scaling limit agrees with that obtained in the dual string theory up to
      wrapping order.

PMID- 29328704
TI  - Short-Range Correlations and the EMC Effect in Effective Field Theory.
AB  - We show that the empirical linear relation between the magnitude of the EMC
      effect in deep inelastic scattering on nuclei and the short-range correlation
      scaling factor a_{2} extracted from high-energy quasielastic scattering at x>=1
      is a natural consequence of scale separation and derive the relationship using
      effective field theory. While the scaling factor a_{2} is a ratio of nuclear
      matrix elements that individually depend on the calculational scheme, we show
      that the ratio is independent of this choice. We perform Green's function Monte
      Carlo calculations with both chiral and Argonne-Urbana potentials to verify this
      and determine the scaling factors for light nuclei. The resulting values for
      ^{3}He and ^{4}He are in good agreement with experimental values. We also present
      results for ^{9}Be and ^{12}C extracted from variational Monte Carlo
      calculations.

PMID- 29328705
TI  - Quantum Triple Point and Quantum Critical End Points in Metallic Magnets.
AB  - In low-temperature metallic magnets, ferromagnetic (FM) and antiferromagnetic
      (AFM) orders can exist, adjacent to one another or concurrently, in the phase
      diagram of a single system. We show that universal quantum effects qualitatively
      alter the known phase diagrams for classical magnets. They shrink the region of
      concurrent FM and AFM order, change various transitions from second to first
      order, and, in the presence of a magnetic field, lead to either a quantum triple
      point where the FM, AFM, and paramagnetic phases all coexist or a quantum
      critical end point.

PMID- 29328706
TI  - Observation of Slow Dynamics near the Many-Body Localization Transition in One
      Dimensional Quasiperiodic Systems.
AB  - In the presence of sufficiently strong disorder or quasiperiodic fields, an
      interacting many-body system can fail to thermalize and become many-body
      localized. The associated transition is of particular interest, since it occurs
      not only in the ground state but over an extended range of energy densities. So
      far, theoretical studies of the transition have focused mainly on the case of
      true-random disorder. In this work, we experimentally and numerically investigate
      the regime close to the many-body localization transition in quasiperiodic
      systems. We find slow relaxation of the density imbalance close to the
      transition, strikingly similar to the behavior near the transition in true-random
      systems. This dynamics is found to continuously slow down upon approaching the
      transition and allows for an estimate of the transition point. We discuss
      possible microscopic origins of these slow dynamics.

PMID- 29328707
TI  - Second Sound in Systems of One-Dimensional Fermions.
AB  - We study sound in Galilean invariant systems of one-dimensional fermions. At low
      temperatures, we find a broad range of frequencies in which in addition to the
      waves of density there is a second sound corresponding to the ballistic
      propagation of heat in the system. The damping of the second sound mode is weak,
      provided the frequency is large compared to a relaxation rate that is
      exponentially small at low temperatures. At lower frequencies, the second sound
      mode is damped, and the propagation of heat is diffusive.

PMID- 29328708
TI  - Liquid-Gas Transitions in Steady Heat Conduction.
AB  - We study liquid-gas transitions of heat conduction systems in contact with two
      heat baths under constant pressure in the linear response regime. On the basis of
      local equilibrium thermodynamics, we propose an equality with a global
      temperature, which determines the volume near the equilibrium liquid-gas
      transition. We find that the formation of the liquid-gas interface is accompanied
      by a discontinuous change in the volume when increasing the mean temperature of
      the baths. A supercooled gas near the interface is observed as a stable steady
      state.

PMID- 29328709
TI  - Topological Vortex and Knotted Dissipative Optical 3D Solitons Generated by 2D
      Vortex Solitons.
AB  - We predict a new class of three-dimensional (3D) topological dissipative optical
      one-component solitons in homogeneous laser media with fast saturable absorption.
      Their skeletons formed by vortex lines where the field vanishes are tangles,
      i.e., N_{c} knotted or unknotted, linked or unlinked closed lines and M unclosed
      lines that thread all the closed lines and end at the infinitely far soliton
      periphery. They are generated by embedding two-dimensional laser solitons or
      their complexes in 3D space after their rotation around an unclosed, infinite
      vortex line with topological charge M_{0} (N_{c}, M, and M_{0} are integers).
      With such structure propagation, the "hula-hoop" solitons form; their stability
      is confirmed numerically. For the solitons found, all vortex lines have unit
      topological charge: the number of closed lines N_{c}=1 and 2 (unknots, trefoils,
      and Solomon knots links); unclosed vortex lines are unknotted and unlinked, their
      number M=1, 2, and 3.

PMID- 29328710
TI  - Ultrafast Charge Transfer Processes Accompanying KLL Auger Decay in Aqueous KCl
      Solution.
AB  - X-ray photoelectron and KLL Auger spectra were measured for the K^{+} and Cl^{-}
      ions in aqueous KCl solution. While the XPS spectra of these ions have similar
      structures, both exhibiting only weak satellites near the main line, the Auger
      spectra differ dramatically. Contrary to the chloride case, a very strong extra
      peak was found in the Auger spectrum of K^{+} at the low kinetic energy side of
      the ^{1}D state. Using the equivalent core model and ab initio calculations this
      spectral feature was assigned to electron transfer processes from solvent water
      molecules to the solvated cation. The observed charge transfer processes are
      suggested to play an important role in charge redistribution following single and
      multiple core-hole creation in atoms and molecules placed into environment.

PMID- 29328711
TI  - Measurement of the Frequency of the 2 ^{3}S-2 ^{3}P Transition of ^{4}He.
AB  - The 2 ^{3}S-2 ^{3}P transition of ^{4}He was measured by comb-linked laser
      spectroscopy using a transverse-cooled atomic beam. The centroid frequency was
      determined to be 276 736 495 600.0(1.4) kHz, with a fractional uncertainty of
      5.1*10^{-12}. This value is not only more accurate but also differs by as much as
      -49.5  kHz (20sigma) from the previous result given by [Cancio Pastor et al.,
      Phys. Rev. Lett. 92, 023001 (2004)PRLTAO0031-900710.1103/PhysRevLett.92.023001;
      Cancio Pastor et al.Phys. Rev. Lett.97, 139903(E)
      (2006)10.1103/PhysRevLett.97.139903; Cancio Pastor et al.Phys. Rev. Lett.108,
      143001 (2012)10.1103/PhysRevLett.108.143001]. In combination with ongoing
      theoretical calculations, this work may allow the most accurate determination of
      the nuclear charge radius of helium.

PMID- 29328712
TI  - Recoil Effect on the g Factor of Li-Like Ions.
AB  - The nuclear recoil effect on the g factor of Li-like ions is evaluated. The one
      electron recoil contribution is treated within the framework of the rigorous QED
      approach to the first order in the electron-to-nucleus mass ratio m/M and to all
      orders in the parameter alphaZ. These calculations are performed in a range Z=3
      92. The two-electron recoil term is calculated for low- and middle-Z ions within
      the Breit approximation using a four-component approach. The results for the two
      electron recoil part obtained in the Letter strongly disagree with the previous
      calculations performed using an effective two-component Hamiltonian. The obtained
      value for the recoil effect is used to calculate the isotope shift of the g
      factor of Li-like ^{A}Ca^{17+} with A=40 and A=48 which was recently measured. It
      is found that the new theoretical value for the isotope shift is closer to the
      experimental one than the previously obtained value.

PMID- 29328713
TI  - Egalitarianism among Bubbles in Porous Media: An Ostwald Ripening Derived
      Anticoarsening Phenomenon.
AB  - We show that smaller gas bubbles grow at the expense of larger bubbles and all
      bubbles approach the same surface curvature after long times in porous media.
      This anticoarsening effect is contrary to typical Ostwald ripening and leads to
      uniformly sized bubbles in a homogeneous medium. Evolution dynamics of bubble
      populations were measured, and mathematical models were developed that fit the
      experimental data well. Ostwald ripening is shown to be the driving mechanism in
      this anticoarsening phenomenon; however, the relationship between surface
      curvature and bubble size determined by the pore-throat geometric confinement
      reverses the ripening direction.

PMID- 29328714
TI  - Experimental Observation of Two Features Unexpected from the Classical Theories
      of Rubber Elasticity.
AB  - Although the elastic modulus of a Gaussian chain network is thought to be
      successfully described by classical theories of rubber elasticity, such as the
      affine and phantom models, verification experiments are largely lacking owing to
      difficulties in precisely controlling of the network structure. We prepared well
      defined model polymer networks experimentally, and measured the elastic modulus G
      for a broad range of polymer concentrations and connectivity probabilities, p. In
      our experiment, we observed two features that were distinct from those predicted
      by classical theories. First, we observed the critical behavior G~|p
      p_{c}|^{1.95} near the sol-gel transition. This scaling law is different from the
      prediction of classical theories, but can be explained by analogy between the
      electric conductivity of resistor networks and the elasticity of polymer
      networks. Here, p_{c} is the sol-gel transition point. Furthermore, we found that
      the experimental G-p relations in the region above C^{*} did not follow the
      affine or phantom theories. Instead, all the G/G_{0}-p curves fell onto a single
      master curve when G was normalized by the elastic modulus at p=1, G_{0}. We show
      that the effective medium approximation for Gaussian chain networks explains this
      master curve.

PMID- 29328715
TI  - Universality and Stability of the Edge States of Chiral-Symmetric Topological
      Semimetals and Surface States of the Luttinger Semimetal.
AB  - We theoretically demonstrate that the chiral structure of the nodes of nodal
      semimetals is responsible for the existence and universal local properties of the
      edge states in the vicinity of the nodes. We perform a general analysis of the
      edge states for an isolated node of a 2D semimetal, protected by chiral symmetry
      and characterized by the topological winding number N. We derive the asymptotic
      chiral-symmetric boundary conditions and find that there are N+1 universal
      classes of them. The class determines the numbers of flatband edge states on
      either side off the node in the 1D spectrum and the winding number N gives the
      total number of edge states. We then show that the edge states of chiral nodal
      semimetals are robust: they persist in a finite-size stability region of
      parameters of chiral-asymmetric terms. This significantly extends the notion of
      2D and 3D topological nodal semimetals. We demonstrate that the Luttinger model
      with a quadratic node for j=3/2 electrons is a 3D topological semimetal in this
      new sense and predict that alpha-Sn, HgTe, possibly Pr_{2}Ir_{2}O_{7}, and many
      other semimetals described by it are topological and exhibit surface states.

PMID- 29328716
TI  - Group Velocity Engineering of Confined Ultrafast Magnons.
AB  - Quantum confinement permits the existence of multiple terahertz magnon modes in
      atomically engineered ultrathin magnetic films and multilayers. By means of spin
      polarized high-resolution electron energy-loss spectroscopy, we report on the
      direct experimental detection of all exchange-dominated terahertz confined magnon
      modes in a 3 ML Co film. We demonstrate that, by tuning the structural and
      magnetic properties of the Co film, through its epitaxial growth on different
      surfaces, e.g., Ir(001), Cu(001), and Pt(111), one can achieve entirely different
      in-plane magnon dispersions, characterized by positive and negative group
      velocities. Our first-principles calculations show that spin-dependent many-body
      correlation effects in Co films play an important role in the determination of
      the energies of confined magnon modes. Our results suggest a pathway towards the
      engineering of the group velocity of confined ultrafast magnons.

PMID- 29328717
TI  - Excitation Spectra in Crystal Plasticity.
AB  - Plastically deforming crystals exhibit scale-free fluctuations that are similar
      to those observed in driven disordered elastic systems close to depinning, but
      the nature of the yielding critical point is still debated. Here, we study the
      marginal stability of ensembles of dislocations and compute their excitation
      spectrum in two and three dimensions. Our results show the presence of a
      singularity in the distribution of excitation stresses, i.e., the stress needed
      to make a localized region unstable, that is remarkably similar to the one
      measured in amorphous plasticity and spin glasses. These results allow us to
      understand recent observations of extended criticality in bursty crystal
      plasticity and explain how they originate from the presence of a pseudogap in the
      excitation spectrum.

PMID- 29328718
TI  - Charge Catastrophe and Dielectric Breakdown During Exposure of Organic Thin Films
      to Low-Energy Electron Radiation.
AB  - The effects of exposure to ionizing radiation are central in many areas of
      science and technology, including medicine and biology. Absorption of UV and soft
      x-ray photons releases photoelectrons, followed by a cascade of lower energy
      secondary electrons with energies down to 0 eV. While these low energy electrons
      give rise to most chemical and physical changes, their interactions with soft
      materials are not well studied or understood. Here, we use a low energy electron
      microscope to expose thin organic resist films to electrons in the range 0-50 eV,
      and to analyze the energy distribution of electrons returned to the vacuum. We
      observe surface charging that depends strongly and nonlinearly on electron energy
      and electron beam current, abruptly switching sign during exposure. Charging can
      even be sufficiently severe to induce dielectric breakdown across the film. We
      provide a simple but comprehensive theoretical description of these phenomena,
      identifying the presence of a cusp catastrophe to explain the sudden switching
      phenomena seen in the experiments. Surprisingly, the films undergo changes at all
      incident electron energies, starting at ~0  eV.

PMID- 29328719
TI  - Breakdown of the Chiral Anomaly in Weyl Semimetals in a Strong Magnetic Field.
AB  - The low-energy quasiparticles of Weyl semimetals are a condensed-matter
      realization of the Weyl fermions introduced in relativistic field theory. Chiral
      anomaly, the nonconservation of the chiral charge under parallel electric and
      magnetic fields, is arguably the most important phenomenon of Weyl semimetals and
      has been explained as an imbalance between the occupancies of the gapless, zeroth
      Landau levels with opposite chiralities. This widely accepted picture has served
      as the basis for subsequent studies. Here we report the breakdown of the chiral
      anomaly in Weyl semimetals in a strong magnetic field based on ab initio
      calculations. A sizable energy gap that depends sensitively on the direction of
      the magnetic field may open up due to the mixing of the zeroth Landau levels
      associated with the opposite-chirality Weyl points that are away from each other
      in the Brillouin zone. Our study provides a theoretical framework for
      understanding a wide range of phenomena closely related to the chiral anomaly in
      topological semimetals, such as magnetotransport, thermoelectric responses, and
      plasmons, to name a few.

PMID- 29328720
TI  - Real-Time Dynamics and Phase Separation in a Holographic First-Order Phase
      Transition.
AB  - We study the fully nonlinear time evolution of a holographic system possessing a
      first order phase transition. The initial state is chosen in the spinodal region
      of the phase diagram, and it includes an inhomogeneous perturbation in one of the
      field theory directions. The final state of the time evolution shows a clear
      phase separation in the form of domain formation. The results indicate the
      existence of a very rich class of inhomogeneous black hole solutions.

PMID- 29328721
TI  - Phase Coexistence in Two-Dimensional Passive and Active Dumbbell Systems.
AB  - We demonstrate that there is a macroscopic coexistence between regions with
      hexatic order and regions in the liquid or gas phase over a finite interval of
      packing fractions in active dumbbell systems with repulsive power-law
      interactions in two dimensions. In the passive limit, this interval remains
      finite, similar to what has been found in two-dimensional systems of hard and
      soft disks. We did not find discontinuous behavior upon increasing activity from
      the passive limit.

PMID- 29328722
TI  - Perfect Spin Filter by Periodic Drive of a Ferromagnetic Quantum Barrier.
AB  - We consider the problem of particle tunneling through a periodically driven
      ferromagnetic quantum barrier connected to two leads. The barrier is modeled by
      an impurity site representing a ferromagnetic layer or a quantum dot in a tight
      binding Hamiltonian with a local magnetic field and an ac-driven potential, which
      is solved using the Floquet formalism. The repulsive interactions in the quantum
      barrier are also taken into account. Our results show that the time-periodic
      potential causes sharp resonances of perfect transmission and reflection, which
      can be tuned by the frequency, the driving strength, and the magnetic field. We
      demonstrate that a device based on this configuration could act as a highly
      tunable spin valve for spintronic applications.

PMID- 29328723
TI  - Second-Order Temporal Interference with Thermal Light: Interference beyond the
      Coherence Time.
AB  - We report the observation of a counterintuitive phenomenon in multipath
      correlation interferometry with thermal light. The intensity correlation between
      the outputs of two unbalanced Mach-Zehnder interferometers (UMZIs) with two
      classically correlated beams of thermal light at the input exhibits genuine
      second-order interference with the visibility of 1/3. Surprisingly, the second
      order interference does not degrade at all no matter how much the path length
      difference in each UMZI is increased beyond the coherence length of the thermal
      light. Moreover, the second-order interference is dependent on the difference of
      the UMZI phases. These results differ substantially from those of the entangled
      photon Franson interferometer, which exhibits two-photon interference dependent
      on the sum of the UMZI phases and the interference vanishes as the path length
      difference in each UMZI exceeds the coherence length of the pump laser. Our work
      offers deeper insight into the interplay between interference and coherence in
      multiphoton interferometry.

PMID- 29328724
TI  - Origins of Singlet Fission in Solid Pentacene from an ab initio Green's Function
      Approach.
AB  - We develop a new first-principles approach to predict and understand rates of
      singlet fission with an ab initio Green's-function formalism based on many-body
      perturbation theory. Starting with singlet and triplet excitons computed from a
      GW plus Bethe-Salpeter equation approach, we calculate the exciton-biexciton
      coupling to lowest order in the Coulomb interaction, assuming a final state
      consisting of two noninteracting spin-correlated triplets with finite center-of
      mass momentum. For crystalline pentacene, symmetries dictate that the only purely
      Coulombic fission decay process from a bright singlet state requires a final
      state consisting of two inequivalent nearly degenerate triplets of nonzero, equal
      and opposite, center-of-mass momenta. For such a process, we predict a singlet
      lifetime of 30-70 fs, in very good agreement with experimental data, indicating
      that this process can dominate singlet fission in crystalline pentacene. Our
      approach is general and provides a framework for predicting and understanding
      multiexciton interactions in solids.

PMID- 29328725
TI  - Realization of a Hole-Doped Mott Insulator on a Triangular Silicon Lattice.
AB  - The physics of doped Mott insulators is at the heart of some of the most exotic
      physical phenomena in materials research including insulator-metal transitions,
      colossal magnetoresistance, and high-temperature superconductivity in layered
      perovskite compounds. Advances in this field would greatly benefit from the
      availability of new material systems with a similar richness of physical
      phenomena but with fewer chemical and structural complications in comparison to
      oxides. Using scanning tunneling microscopy and spectroscopy, we show that such a
      system can be realized on a silicon platform. The adsorption of one-third
      monolayer of Sn atoms on a Si(111) surface produces a triangular surface lattice
      with half filled dangling bond orbitals. Modulation hole doping of these dangling
      bonds unveils clear hallmarks of Mott physics, such as spectral weight transfer
      and the formation of quasiparticle states at the Fermi level, well-defined Fermi
      contour segments, and a sharp singularity in the density of states. These
      observations are remarkably similar to those made in complex oxide materials,
      including high-temperature superconductors, but highly extraordinary within the
      realm of conventional sp-bonded semiconductor materials. It suggests that exotic
      quantum matter phases can be realized and engineered on silicon-based materials
      platforms.

PMID- 29328726
TI  - Atom Interferometry with the Sr Optical Clock Transition.
AB  - We report on the realization of a matter-wave interferometer based on single
      photon interaction on the ultranarrow optical clock transition of strontium
      atoms. We experimentally demonstrate its operation as a gravimeter and as a
      gravity gradiometer. No reduction of interferometric contrast was observed for a
      total interferometer time up to ~10  ms, limited by geometric constraints of the
      apparatus. Single-photon interferometers represent a new class of high-precision
      sensors that could be used for the detection of gravitational waves in so far
      unexplored frequency ranges and to enlighten the boundary between quantum
      mechanics and general relativity.

PMID- 29328727
TI  - Exact Time-Dependent Exchange-Correlation Potential in Electron Scattering
      Processes.
AB  - We identify peak and valley structures in the exact exchange-correlation
      potential of time-dependent density functional theory that are crucial for time
      resolved electron scattering in a model one-dimensional system. These structures
      are completely missed by adiabatic approximations that, consequently,
      significantly underestimate the scattering probability. A recently proposed
      nonadiabatic approximation is shown to correctly capture the approach of the
      electron to the target when the initial Kohn-Sham state is chosen judiciously,
      and it is more accurate than standard adiabatic functionals but ultimately fails
      to accurately capture reflection. These results may explain the underestimation
      of scattering probabilities in some recent studies on molecules and surfaces.

PMID- 29328728
TI  - Locally Optimal Control of Complex Networks.
AB  - It has recently been shown that the minimum energy solution of the control
      problem for a linear system produces a control trajectory that is nonlocal. An
      issue then arises when the dynamics represents a linearization of the underlying
      nonlinear dynamics of the system where the linearization is only valid in a local
      region of the state space. Here we provide a solution to the problem of optimally
      controlling a linearized system by deriving a time-varying set that represents
      all possible control trajectories parametrized by time and energy. As long as the
      control action terminus is defined within this set, the control trajectory is
      guaranteed to be local. If the desired terminus of the control action is far from
      the initial state, a series of local control actions can be performed in series,
      relinearizing the dynamics at each new position.

PMID- 29328729
TI  - Ultracold Atoms in a Square Lattice with Spin-Orbit Coupling: Charge Order,
      Superfluidity, and Topological Signatures.
AB  - We present an ab initio, numerically exact study of attractive fermions in square
      lattices with Rashba spin-orbit coupling. The ground state of this system is a
      supersolid, with coexisting charge and superfluid order. The superfluid is
      composed of both singlet and triplet pairs induced by spin-orbit coupling. We
      perform large-scale calculations using the auxiliary-field quantum Monte Carlo
      method to provide the first full, quantitative description of the charge, spin,
      and pairing properties of the system. In addition to characterizing the exotic
      physics, our results will serve as essential high-accuracy benchmarks for the
      intense theoretical and especially experimental efforts in ultracold atoms to
      realize and understand an expanding variety of quantum Hall and topological
      superconductor systems.

PMID- 29328730
TI  - Spectral Decomposition of Missing Transverse Energy at Hadron Colliders.
AB  - We propose a spectral decomposition to systematically extract information of dark
      matter at hadron colliders. The differential cross section of events with missing
      transverse energy (E_{T}) can be expressed by a linear combination of basis
      functions. In the case of s-channel mediator models for dark matter particle
      production, basis functions are identified with the differential cross sections
      of subprocesses of virtual mediator and visible particle production while the
      coefficients of basis functions correspond to dark matter invariant mass
      distribution in the manner of the Kallen-Lehmann spectral decomposition. For a
      given E_{T} data set and mediator model, we show that one can differentiate a
      certain dark matter-mediator interaction from another through spectral
      decomposition.

PMID- 29328731
TI  - High-Resolution Quantum Sensing with Shaped Control Pulses.
AB  - We investigate the application of amplitude-shaped control pulses for enhancing
      the time and frequency resolution of multipulse quantum sensing sequences. Using
      the electronic spin of a single nitrogen-vacancy center in diamond and up to 10
      000 coherent microwave pulses with a cosine square envelope, we demonstrate 0.6
      ps timing resolution for the interpulse delay. This represents a refinement by
      over 3 orders of magnitude compared to the 2-ns hardware sampling. We apply the
      method for the detection of external ac magnetic fields and nuclear magnetic
      resonance signals of ^{13}C spins with high spectral resolution. Our method is
      simple to implement and especially useful for quantum applications that require
      fast phase gates, many control pulses, and high fidelity.

PMID- 29328732
TI  - Asymptotically Safe Standard Model via Vectorlike Fermions.
AB  - We construct asymptotically safe extensions of the standard model by adding
      gauged vectorlike fermions. Using large number-of-flavor techniques we argue that
      all gauge couplings, including the hypercharge and, under certain conditions, the
      Higgs coupling, can achieve an interacting ultraviolet fixed point.

PMID- 29328733
TI  - Understanding Quality Factor Degradation in Superconducting Niobium Cavities at
      Low Microwave Field Amplitudes.
AB  - In niobium superconducting radio frequency (SRF) cavities for particle
      acceleration, a decrease of the quality factor at lower fields-a so-called low
      field Q slope or LFQS-has been a long-standing unexplained effect. By extending
      the high Q measurement techniques to ultralow fields, we discover two previously
      unknown features of the effect: (i) saturation at rf fields lower than
      E_{acc}~0.1  MV/m; (ii) strong degradation enhancement by growing thicker niobium
      pentoxide. Our findings suggest that the LFQS may be caused by the two level
      systems in the natural niobium oxide on the inner cavity surface, thereby
      identifying a new source of residual resistance and providing guidance for
      potential nonaccelerator low-field applications of SRF cavities.

PMID- 29328734
TI  - Connecting the Kuramoto Model and the Chimera State.
AB  - Since its discovery in 2002, the chimera state has frequently been described as a
      counterintuitive, puzzling phenomenon. The Kuramoto model, in contrast, has
      become a celebrated paradigm useful for understanding a range of phenomena
      related to phase transitions, synchronization, and network effects. Here we show
      that the chimera state can be understood as emerging naturally through a symmetry
      breaking bifurcation from the Kuramoto model's partially synchronized state. Our
      analysis sheds light on recent observations of chimera states in laser arrays,
      chemical oscillators, and mechanical pendula.

PMID- 29328735
TI  - Universal Entropy of Conformal Critical Theories on a Klein Bottle.
AB  - We show that rational conformal field theories in 1+1 dimensions on a Klein
      bottle, with a length L and width beta, satisfying L?beta, have a universal
      entropy. This universal entropy depends on the quantum dimensions of the primary
      fields and can be accurately extracted by taking a proper ratio between the Klein
      bottle and torus partition functions, enabling the characterization of conformal
      critical theories. The result is checked against exact calculations in quantum
      spin-1/2 XY and Ising chains.

PMID- 29328736
TI  - Dynamical Formation of Kerr Black Holes with Synchronized Hair: An Analytic
      Model.
AB  - East and Pretorius have successfully evolved, using fully nonlinear numerical
      simulations, the superradiant instability of the Kerr black hole (BH) triggered
      by a massive, complex vector field. Evolutions terminate in stationary states of
      a vector field condensate synchronized with a rotating BH horizon. We show that
      these end points are fundamental states of Kerr BHs with synchronized Proca hair.
      Motivated by the "experimental data" from these simulations, we suggest a
      universal (i.e., field-spin independent), analytic model for the subset of BHs
      with synchronized hair that possess a quasi-Kerr horizon, applicable in the weak
      hair regime. Comparing this model with fully nonlinear numerical solutions of BHs
      with a synchronized scalar or Proca hair, we show that the model is accurate for
      hairy BHs that may emerge dynamically from superradiance, whose domain we
      identify.

PMID- 29328737
TI  - Simple mastectomy under hypnosis: A case study approach.
AB  - There is a clear inverse relationship between preoperative anxiety and effective
      anaesthesia and recovery. Studies have shown that perioperative anxiety can be
      detrimental to the efficacy of recovery. In order to mitigate the perioperative
      anaesthetic risk to the patient, perioperative care must be inclusive of
      psychological as well as physiological elements. Therefore, when planning and
      implementing care for the surgical patient alternative interventions, such as
      hypnosis, should be considered when presented with difficult patient factors,
      such as crippling anxiety. This article takes on a case study approach to
      critically analyse and appraise the holistic care of a patient undergoing a
      simple mastectomy with hypnosis as the primary anaesthesia.

PMID- 29328738
TI  - The rise of inventory management in operating theatre departments.
AB  - The procurement and inventory management challenges within our healthcare sector
      have been the subject of debate for some time, but with new government
      initiatives recently introduced, procurement and inventory management have become
      the new areas of focus behind muchneeded change within the NHS back-office.

PMID- 29328739
TI  - From novice to expert: a surgical care practitioner's reflection on their role
      development.
AB  - As co-lead for the AfPP Advancing Surgical Roles Specialist Interest Group, I was
      recently asked about which procedures a surgical care practitioner (SCP) can be
      trained to undertake and how the SCP role can be developed fully within the remit
      of the surgical team. This question enabled me to reflect upon and explore the
      development of my own role of a vascular and general SCP using Benner's
      adaptation of the Dreyfus' expertise acquisition model that describes the
      transition that nurses and, one could argue, all healthcare professionals make
      from novice to expert practitioners (Benner 1984) (Figure 1).

PMID- 29328740
TI  - Using a STOP/GO protocol in the preoperative area to increase patient safety.
AB  - A multitude of surgeries are performed each year and 15% of cases have an adverse
      event, most of which are preventable. A culture of safety must be adopted by the
      entire surgical team. A preoperative checklist in addition to the intraoperative
      checklist can help decrease errors. We adapted a Stop/Go process in the
      preoperative area which had to be completed prior to moving the patient into the
      operating room. We examined adverse events before and after this process. Adverse
      events decreased from 1.5% to nearly 0% over the time examined. The Stop/Go
      preoperative checklist, adapted to our specific operating room needs, helped to
      decrease adverse events.

PMID- 29328741
TI  - Perioperative teamwork for the patient with a shared airway: a case study.
AB  - Teamwork is an essential element of perioperative care. Shared airway surgery
      requires additional considerations for the perioperative team. This article
      analyses a case study of a patient undergoing thyroid surgery. Whilst the
      anaesthetic team is responsible for maintaining the patient's airway, the theatre
      and surgical teams have their own individual roles to assist in airway management
      and surgical care.

PMID- 29328742
TI  - Pragmatic recycling of paper and cardboard in the operating theatre: an audit.
AB  - Despite recent legislation introduced in Scotland and motivated recycling at
      home, very little recycling exists within theatre environments. This study
      audited the introduction of recycling of paper and cardboard. All waste within a
      single operating theatre was collected by a dedicated team for 20 surgical cases.
      The collection of clean paper and cardboard packaging was limited to the theatre
      preparation room (TPR) and anaesthetic room (AR). No waste segregation was
      attempted within the operating theatre itself. The results showed that the AR
      produced a mean weight of 1.3kg of waste per patient (50% paper and cardboard),
      and the TPR produced 3.05kg per patient (33% general waste; 44% paper; 23%
      cardboard). Recycling saved a mean of L0.51 per case. The 54kg of recycled bags
      produced during the study saved 25kg CO2 emissions. This study describes a
      pragmatic method to recycle paper and cardboard within the TPR and AR. There are
      significant potential financial and environmental savings to be achieved.

PMID- 29328743
TI  - Man behind the laryngoscopy is important.
AB  - Tracheal intubation is the most fundamental and effective resuscitation skill in
      many emergency situations. It is also performed to facilitate various surgical
      procedures and mechanical ventilation in critically ill patients. Tracheal
      intubation is also one of the most commonly taught clinical skills.

PMID- 29328744
TI  - ASA grading: a step forward.
AB  - ASA grading is universally used as a predictor of postoperative outcome. It has
      been incorporated as part of the WHO checklist to make everyone involved in
      patient care aware of the patient's physical status, and infer a possible
      postoperative outcome. Everyone in theatre involved in the care of the patient is
      aware of the patient's physical status, except the patient! This article is an
      innovative way of representing ASA physical status to enhance patient involvement
      and understanding, and to facilitate shared decision making.

PMID- 29328745
TI  - Airway safety in a patient with submandibular swelling.
AB  - A fifty-eight year old gentleman (CH) with a five-day history of toothache
      presented to the emergency department (ED) with increasing pain with associated
      submandibular swelling over the last 24-hours. He was an unkempt gentleman who
      had not consulted his general practitioner or dentist in many years, was unaware
      of any significant past medical history and was not on any regular medication. He
      was an obese gentleman with a BMI of 56.

PMID- 29328746
TI  - Operating department practitioners care of the patient with diabetes in the
      perioperative period.
AB  - Diabetes mellitus (DM) is a of group metabolic diseases which are defined by
      hyperglycaemia affecting multiple organs. The condition is found in people of all
      ages and ethnicities. Diabetes mellitus affects 180 million people worldwide and
      increasing numbers of patients are presenting with diabetic complications and the
      need for surgical intervention. This article describes the pathophysiology of DM
      and the management of the condition, particularly type I and type 2, in the
      perioperative phase of the surgical patient journey.

PMID- 29328747
TI  - Critical incident analysis: Equip to avoid failure.
AB  - This work is set in the context of perioperative practice in difficult airway
      management. It integrates a root cause analysis and fish bone technique to
      investigate a critical incident in temporary yet crucial equipment failure. Risk
      management and incident reporting is analysed alongside human factors in the
      operating theatre environment. Finally, recommendations for risk reduction,
      vigilance and checking vital airway equipment are made in anaesthetic practice.

PMID- 29328749
TI  - Thromboembolic diseases and the use of vena cava filters.
AB  - Mr GW is a 77-year-old gentleman who is hoping to have a total knee replacement
      of his left knee. He underwent a knee replacement on the right in 2011 under
      spinal anaesthetic, where his postoperative period was complicated by a saddle
      pulmonary embolus (PE).

PMID- 29328748
TI  - Analysis of neuro-theatre utilisation and reasons for cancellation to improve
      efficiency and productivity.
AB  - In neurosurgery, much emphasis has recently been placed on theatre cancellation
      and time utilization as a key hospital management performance indicator. We
      sought to evaluate our unit's theatre throughput efficiency and identify the
      causes of elective surgery cancellations. We retrospectively audited all
      scheduled elective neurosurgical procedures over a period of nine months. Mean
      theatre utilization time was 47.0%. The common causes of cancellations were lack
      of theatre time (32%), non-availability of beds in recovery room (18.6%), and
      insufficient preoperative patient preparation (5.5%). Inefficiencies were noted
      in turnover of patients and inaccurate prediction of operative time. Our theatre
      utilization time is consistent with available literature; however, cancellations
      of elective surgery waste valuable operative time and resources. The study
      concludes that a multi-dimensional approach must be taken to improve theatre
      utilization and reduce cancellation rates. A pre-assessment clinic has been
      introduced in order to reduce cancellation rates.

PMID- 29328750
TI  - Adaptation of a tool to assess non-technical skills of scrub practitioners in
      Denmark.
AB  - The aim of this study was to adapt the Scottish tool, Scrub Practitioners List of
      Intraoperative Non-Technical Skills, to Danish organisation and culture. With an
      explorative and qualitative approach, four group interviews with scrub
      practitioners, surgeons and anaesthesia staff were conducted. The main
      differences found were related to communication and teamwork regarding scrub
      practitioners focus on the team and speaking up. Differences in the non-technical
      skills described in the behavioural markers are perhaps explained by cultural
      differences between Scotland and Denmark. A new tool for scrub practitioners in
      Denmark was adapted.

PMID- 29328751
TI  - A comparative prospective cohort study comparing physical exam to ultrasound for
      identifying the cricoid cartilage.
AB  - Applying cricoid pressure is a common practice when intubating patients thought
      to be at risk of pulmonary aspiration. Recently, the perceived benefits of
      applying cricoid pressure have been questioned. Prior research has shown that
      cricoid pressure is applied incorrectly and that palpation of adjacent anatomy of
      the cricothyroid membrane is also inaccurate. We compared physical palpation to
      ultrasound for identifying the location of the cricoid cartilage using a total of
      50 assessments. The median distance to target was 10 mm. We concluded that
      palpation is an inaccurate method to locate the cricoid cartilage in the studied
      population.

PMID- 29328752
TI  - Literature review: Awareness of anaesthesia.
AB  - A review of qualitative literature regarding awareness under general anaesthesia
      was undertaken, this term being defined as full consciousness during surgery with
      explicit recall of events. This study was designed to explore perioperative
      practitioner knowledge, skill base and education on the subject of awareness. It
      also explores the practitioner role in, looking out for and rectification, their
      obligations to the patient and their statutory bodies, as well as adherence to
      standards of conduct, performance and ethics. The article aims to shed light on
      this phenomenon and to empower a practitioner to act for the benefit of the
      service user.

PMID- 29328753
TI  - A critical analysis of the perioperative management of patients with Ehlers
      Danlos type IV (vascular) syndrome.
AB  - This article discusses the perioperative care needs of patients with Ehlers
      Danlos type IV (vascular) syndrome. Ehlers Danlos syndrome (EDS) is a heritable
      group of connective tissue disorders characterised by varying degrees of tissue,
      blood vessel and internal organ fragility as well as skin and joint hypermobility
      (De Paepe and Malfait 2012).

PMID- 29328754
TI  - Pioneers of pneumonectomy for carcinoma of the lung.
AB  - The first reports of successful pneumonectomy for carcinoma.

PMID- 29328755
TI  - NICE guidance on interventional procedures: the perspectives of a new Clinical
      Advisor.
AB  - A commitment to delivering the very best care to patients is central to the work
      of all clinicians. The introduction of new interventional procedures to clinical
      practice is essential to improve patient care. Yet, history tells us that when
      interventional procedures are introduced without due regard to their efficacy and
      safety there can be significant adverse consequences for the patient (DH 2001).
      Nearly three decades ago the concept of Clinical Governance was introduced to the
      NHS to address these concerns. The aim was to allow continuous improvement in the
      quality of services while safeguarding patient safety and ensuring high standards
      of care (Scally and Donaldson 1998).

PMID- 29328756
TI  - Review of practice: Facilitating normality at caesarean section.
AB  - Expectant women often write detailed birth plans outlining their preferences for
      the birth of their baby. These plans are pushed aside when a caesarean is deemed
      necessary, being replaced with medical decisions in a clinical setting. In the
      busiest maternity unit in the South West, our team are trying to change this
      attitude, encompassing many of the key points of 'normal' birth choices that are
      important to mothers during caesarean section, without compromising clinical
      care.

PMID- 29328758
TI  - Ergonomics: an important factor in the operating room.
AB  - There is a mutual interaction between health and the workplace. Health affects
      the capacity to work and working conditions affect a worker's health. Operating
      rooms (ORs) are stressful, complex settings in which there are ergonomic risk
      factors, such as lifting/moving heavy equipment. Work-related musculoskeletal
      disorders (WRMSDs) can arise due to unhealthy ergonomic conditions. Our study
      showed that nurses had been absent from work and/or retired early due to WRMSDs.
      Good ergonomic conditions in ORs increase nurses' occupational health and safety,
      their job satisfaction and performance. These factors contribute to patient care
      outcomes in a positive way.

PMID- 29328757
TI  - The pathophysiology of coronary heart disease from a student's perspective.
AB  - It is estimated that 2.3 million people in the UK are living with coronary heart
      disease (CHD) (ONS 2014a). It is therefore important to have a deeper
      understanding of the pathophysiology of the condition and an awareness of the
      complex interplay of contributory factors. Written from the perspective of a
      student ODP, this article investigates the aetiology, presentation and
      progression of the disease, and puts CHD into the context of the emerging
      anaesthetic practitioner's practice.

PMID- 29328759
TI  - Astley Cooper's ligation of the abdominal aorta.
AB  - I have to confess that Sir Astley Cooper (1768-1841), of Guy's Hospital, is high
      on my list of surgical heroes. Indeed, I chose his remarkable and successful
      operation of amputation at the hip joint as my first article in this series.
      Among his other astonishing firsts must surely be his ligation of the abdominal
      aorta for a patient with a leaking iliac aneurysm.

PMID- 29328760
TI  - Leadership: briefing and debriefing in the operating room.
AB  - Steelman (2014) stated that the concept of briefing and debriefing used in
      operating theatres derived from the airline industry in the 1970s. There had been
      a series of devastating air crashes and the airline industry had come under
      severe public scrutiny. Investigations identified that, while the crews operating
      these aircrafts were very skilled and knowledgeable, they lacked competence in
      their ability to perform as part of a team.

PMID- 29328761
TI  - Pancreatic cancer: a symptomless killer.
AB  - Pancreatic cancer is the fifth most common cause of cancer death in the UK. This
      disease often remains undiagnosed until it is at a late stage, resulting in the
      majority of tumours being unsuitable for surgical resection. When a diagnosis of
      pancreatic cancer is confirmed, early input from the multi-disciplinary team
      (MDT) is vital. Due to the poor prognosis, the screening and treatment of
      pancreatic cancer remains a considerable challenge for medicine in the 21st
      century.

PMID- 29328762
TI  - Patients' experiences with at-home preoperative skin disinfection before elective
      hip replacement surgery.
AB  - The aim of the study was to describe patients' experiences with preoperative skin
      disinfection carried out in their home before elective hip replacement surgery
      with the aim of lowering the microbial burden and avoiding surgical site
      infections. The literature was reviewed for relevant studies. Optimal
      preparations before surgery depend on patients being able to assimilate
      preoperative information and instructions. The study was based on 14 interviews
      with patients who had undergone elective hip replacement surgery. Data were
      analysed with qualitative manifest content analysis according to Graneheim and
      Lundman (2004). The main categories of findings were: patients' experience of
      obstacles and limitations, the importance of supportive surroundings, and
      personal resources as strength when performing preoperative skin disinfection.
      The findings of this study agree with earlier studies showing a lack of
      compliance to preoperative skin disinfection. The findings also suggest reasons
      for non-compliance. Preoperative skin disinfection involves many important steps
      that need to be accomplished to ensure the maximum effect on microbial burden on
      skin surface. These steps can be difficult for some patient groups. Perioperative
      dialogue is one way to identify patients' individual needs and to help patients
      participate in the process. The study concludes that patients who carried out
      skin disinfection at home before surgery have a great responsibility to prepare
      themselves. The challenge for perioperative nurses who work with preoperative
      information is to identify and individually guide those patients who need
      extended support so that all patients with elective hip replacement surgery
      receive the same quality of care. Further research should focus on how caregivers
      discover individuals with extended needs and on identifying the kind of support
      that is effective to achieve optimal conditions for hip replacement surgery.

PMID- 29328763
TI  - OSA and the bariatric patient.
AB  - Mrs NH is a 49-year-old lady who presented for assessment prior to weight
      reduction surgery.

PMID- 29328764
TI  - Conditional Value of Raising Positive End-Expiratory Pressure to Counter Vigorous
      Breathing Efforts in Injured Lungs.

PMID- 29328765
TI  - Implementing an integrated in-situ coaching, observational audit, and story
      telling intervention to support safe surgery.
AB  - This article describes an intervention that combined in-situ coaching,
      observational audits and story-telling to educate theatre teams at University
      College London Hospitals about the Five steps to safer surgery (NPSA 2010). Our
      philosophy was to educate theatre teams about 'what goes right' (good catches,
      exemplary leadership etc) as well as 'what could be improved'. Results showed
      improvements on 'behavioural reliability' metrics, a 68% increase in near miss
      reporting and a reduction in surgical harm incidents.

PMID- 29328766
TI  - Safer anaesthetic rooms: Human factors/ergonomics analysis of work practices.
AB  - The aim of this study was to analyse the design of anaesthetic rooms using human
      factors and ergonomics (HFE) methods. The methods used were hierarchical task
      analysis, link analysis and anthropometry. The study found several latent design
      errors which negatively affected drug and patient preparation tasks.
      Recommendations include anaesthetic room layout design modifications and system
      level changes. HFE principles provide generic recommendations but specific design
      details may not be generalizable. Further research is needed to explore the
      implementation of system changes.

PMID- 29328767
TI  - Culture, silence and voice: The implications for patient safety in the operating
      theatre.
AB  - Team culture is an important antecedent to safety behaviours such as speaking up.
      A positive safety culture in the operating theatre has been linked to fewer
      adverse events. Psychological safety, a component of safety culture, is the
      belief that the team is safe to take risks such as raising concerns. Power
      dynamics can influence active speaking up behaviour or 'voice'. When theatre team
      members chose to remain silent rather than voice concerns this can be a
      protective or defensive strategy rather than passive inactivity.

PMID- 29328768
TI  - Human factors and non-technical skills: Teamwork.
AB  - Making mistakes is part of being human and human error is normal in all areas of
      life (Bromiley and Mitchell 2009). In some contexts this is of little
      consequence, but in environments where human safety and well-being are at stake
      it is vital that such error is minimised. The operating theatre is one such
      safety critical environment. Research suggests, however, that certain factors
      predispose to human error. Some or all of these factors may be present in the
      operating theatre and, therefore, have the potential to compromise patient
      safety.

PMID- 29328769
TI  - An interview with Martin Bromiley.
AB  - Many of you will have heard of Martin Bromiley and many will have met him over
      the years since he became a prominent figure within the environs of perioperative
      care. Martin came into our lives as a result of the tragic death of his wife
      Elaine Bromiley a 37 year old mother of two who was admitted for an elective
      endoscopic sinus surgery. Elaine suffered major complications during the
      induction of general anaesthesia that resulted in her death due to hypoxic brain
      damage.

PMID- 29328770
TI  - West Midlands Major Trauma Centre Theatre Practitioner Collaborative.
AB  - The following article highlights the establishment of the West Midlands Major
      Trauma Centres (MTC) in April 2012 and specifically the West Midlands Major
      Trauma Centre Theatre Practitioner Collaborative in June 2013. The article looks
      at the involvement of theatre practitioners working as an integral part of the
      emergency department and supporting anaesthetists when attending alerts. There is
      a summary of clinical responsibilities, mentorship opportunities and the
      educational programme associated with the role. The MTC collaborative ensures
      that there is support for individual centres with regular meetings covering
      clinical and educational issues as well as conducting cross site skill
      programmes. The collaborative are working toward a formal approach to a higher
      educational institution, to consider establishing a post graduate training module
      and to prepare theatre practitioners for the role in the emergency department.

PMID- 29328771
TI  - An exploration of the factors that influence the successful implementation of the
      World Health Organization Surgical Safety Checklist.
AB  - This study presents an exploration of the factors which influence the successful
      implementation of the WHO Surgical Safety Checklist. A mixed methodological
      approach using a questionnaire was sent to 348 healthcare professionals in a
      single NHS trust who use the WHO checklist. 103 questionnaires were returned;
      five were incomplete and discarded. Data was analysed from 98 questionnaires.
      Results were evaluated alongside recommendations from a previous audit that took
      place in this trust in 2013. 63% of surgeons and 54% of anaesthetists within the
      trust remain untrained as regards the surgical safety checklist. Sign out was the
      poorest performing component; time out also needed improvement. The biggest
      obstacle in successful implementation was found to be disengagement of the
      surgical team. Simulation and team training can enhance non-technical skills,
      improving communication between staff. The study concludes that differing staff
      perceptions were found to create barriers to successful implementation of the
      checklist. Training of all staff is necessary for effective communication within
      the operating theatre.

PMID- 29328772
TI  - Interprofessional simulation training for perioperative management team
      development and patient safety.
AB  - Establishment of a perioperative management team construct including
      anaesthesiologists, surgeons, nurses, and other medical staff is essential to
      optimize safe surgical care. Simulation based education and training provides a
      unique and effective approach to development of competency and application of
      relevant technical and non-technical perioperative professional skills such as
      meta-cognitive ability, caution, shared decision-making, leadership and
      communication. Development of high functioning perioperative teams can be
      accomplished through simulation based training.

PMID- 29328773
TI  - Simple foot holder saves your theatre practitioner's back: a technical tip.
AB  - We provide a simple technique for foot positioning during preoperative skin
      preparation. Prone headrest made of gel polymer is used to support the patient's
      leg to keep the foot up. This will protect your operating theatre practitioner's
      back avoiding any mechanical back strain. It will also save money by preventing
      sickness and reducing workplace litigation from back injuries.

PMID- 29328774
TI  - The first elective splenectomy.
AB  - Although there had been rare reports in the past of a surgeon removing a
      prolapsed spleen dangling out of a traumatically lacerated abdomen, with recovery
      of the patient, a successful deliberate laparotomy for a pathologically enlarged
      spleen was, as you may imagine, a much more recent event, with all the advantages
      of antiseptic surgery and anaesthesia. In fact, the first such operation was
      actually performed with the mistaken diagnosis of a large ovarian mass.

PMID- 29328775
TI  - Breast Specimen Processing and Reporting With an Emphasis on Margin Evaluation: A
      College of American Pathologists Survey of 866 Laboratories.
AB  - CONTEXT: - The College of American Pathologists (CAP) developed protocols for
      reporting pathologic characteristics of breast cancer specimens, including margin
      status. The Society of Surgical Oncology (SSO) and the American Society for
      Radiation Oncology (ASTRO) published treatment guidelines regarding margins in
      patients with invasive cancer; and SSO, ASTRO, and the American Society of
      Clinical Oncology (ASCO) recently published guidelines for patients with ductal
      carcinoma in situ. OBJECTIVE: - To assess current practices among pathologists
      with regard to the processing/reporting of breast specimens, assess compliance
      with CAP cancer protocols, and assess alignment with SSO/ASTRO and SSO/ASTRO/ASCO
      guidelines. DESIGN: - A survey concerning breast specimen processing/reporting
      was distributed to pathologists enrolled in the CAP Performance Improvement
      Program in Surgical Pathology. RESULTS: - Ninety-four percent (716 of 764
      respondents) and 91% (699 of 769 respondents) define positive margins as "tumor
      on ink" for invasive cancer and ductal carcinoma in situ, respectively, in
      compliance with CAP cancer protocols and with SSO/ASTRO and SSO/ASTRO/ASCO
      guidelines. Of 791 respondents who provided details regarding methods for margin
      evaluation, 608 (77%) exclusively examine perpendicular margins, facilitating
      guideline compliance. However, 183 of 791 respondents (23%) examine en face
      margins in at least a subset of specimens, which may preclude guideline
      compliance in some cases. When separate cavity (shave) margins are examined,
      while 517 of 586 respondents (88%) ink these specimens, 69 of 586 (12%) do not,
      and this may also preclude guideline compliance in some cases. CONCLUSIONS: - A
      substantial proportion of survey participants report margin status for breast
      cancer specimens in a manner consistent with CAP cancer protocols, and in
      alignment with SSO/ASTRO and SSO/ASTRO/ASCO guidelines. However, there are
      opportunities for some laboratories to modify procedures in order to facilitate
      more complete adherence to guidelines.

PMID- 29328776
TI  - More Than a Decade of Molecular Diagnostic Cytopathology Leading Diagnostic and
      Therapeutic Decision-Making.

PMID- 29328777
TI  - Systematic review of developmental care interventions in the neonatal intensive
      care unit since 2006.
AB  - Intervention studies designed to improve neurodevelopmental outcomes of premature
      infants in the neonatal intensive care unit (NICU) were evaluated in this
      systematic review to analyze research methods, to illuminate the effectiveness of
      interventions, and to make recommendations for future research. Google Scholar,
      the Cumulative Index of Nursing and Applied Health Literature, PubMed, and
      Cochrane databases were investigated to identify experimental and quasi
      experimental interventional studies in peer-reviewed journals. Each study was
      assessed in the areas of sample, design, interventional strategies, threats to
      validity, and outcomes. Nineteen articles were reviewed with a variety of
      clustered and individual strategies identified to improve neurodevelopmental
      outcomes of premature infants in the NICU. Developmental care in the NICU appears
      to have some positive effects on the neurodevelopment of preterm infants.
      However, there were a number of limitations identified that threaten the validity
      of the included studies. Going forward, components of developmental care should
      be operationalized more consistently, greater effort should be put into ensuring
      treatment fidelity, and electroencephalogram data should be collected in
      conjunction with behavioral outcome measures.

PMID- 29328778
TI  - Engineering Approaches to Study Cellular Decision Making.
AB  - In their native environment, cells are immersed in a complex milieu of
      biochemical and biophysical cues. These cues may include growth factors, the
      extracellular matrix, cell-cell contacts, stiffness, and topography, and they are
      responsible for regulating cellular behaviors such as adhesion, proliferation,
      migration, apoptosis, and differentiation. The decision-making process used to
      convert these extracellular inputs into actions is highly complex and sensitive
      to changes both in the type of individual cue (e.g., growth factor dose/level,
      timing) and in how these individual cues are combined (e.g.,
      homotypic/heterotypic combinations). In this review, we highlight recent advances
      in the development of engineering-based approaches to study the cellular decision
      making process. Specifically, we discuss the use of biomaterial platforms that
      enable controlled and tailored delivery of individual and combined cues, as well
      as the application of computational modeling to analyses of the complex cellular
      decision-making networks.

PMID- 29328779
TI  - Transforming the Treatment of Schizophrenia in the United States: The RAISE
      Initiative.
AB  - The schizophrenia spectrum disorders are neurodevelopmental illnesses with a
      lifetime prevalence near 1%, producing extensive functional impairment and low
      expectations for recovery. Until recently, treatment in the United States has
      largely attempted to stabilize individuals with chronic schizophrenia. The
      identification and promotion of evidence-based practices for schizophrenia via
      the Patient Outcomes Research Team, combined with international studies
      supporting the value of early intervention, provided the foundation for the
      Recovery After an Initial Schizophrenia Episode (RAISE) project. The RAISE
      studies further supported the value of reducing the duration of untreated
      psychosis and providing a multi-element treatment called coordinated specialty
      care (CSC) to improve outcomes for patients in usual treatment settings. Although
      CSC programs have proliferated rapidly in the United States, many challenges
      remain in the treatment and recovery of individuals with schizophrenia in the
      aftermath of RAISE.

PMID- 29328780
TI  - Risk Factors for Depression: An Autobiographical Review.
AB  - I have been given a priceless opportunity to reflect on my career in the
      remarkably productive field of risk factors for depression. Psychological
      research on depression exploded in the early years of my work. I try to give an
      account of the choices and challenges, and reflect on the influences, some
      calculated and some serendipitous, that determined the paths I have followed. I
      focus mostly on the robust depression risk factors that have influenced my
      research, including dysfunctional cognitions, stressful life events and
      circumstances, parental depression, interpersonal dysfunction, and being female,
      and I cover some of what I did but also the influential work of others. This is a
      selective review of depression research in the past 40 or so years, noting some
      of the big developments that set the stage for the remarkable activity that
      continues today. In the conclusion, there is a brief statement of aspirations for
      future developments in our field.

PMID- 29328781
TI  - Normalization of Deviation: Quotation Error in Human Factors.
AB  - Objective The objective of this paper is to examine quotation error in human
      factors. Background Science progresses through building on the work of previous
      research. This requires accurate quotation. Quotation error has a number of
      adverse consequences: loss of credibility, loss of confidence in the journal, and
      a flawed basis for academic debate and scientific progress. Quotation error has
      been observed in a number of domains, including marine biology and medicine, but
      there has been little or no previous study of this form of error in human
      factors, a domain that specializes in the causes and management of error. Methods
      A study was conducted examining quotation accuracy of 187 extracts from 118
      published articles that cited a control article (Vaughan's 1996 book: The
      Challenger Launch Decision: Risky Technology, Culture, and Deviance at NASA).
      Results Of extracts studied, 12.8% ( n = 24) were classed as inaccurate, with
      87.2% ( n = 163) being classed as accurate. A second dimension of agreement was
      examined with 96.3% ( n = 180) agreeing with the control article and only 3.7% (
      n = 7) disagreeing. The categories of accuracy and agreement form a two by two
      matrix. Conclusion Rather than simply blaming individuals for quotation error,
      systemic factors should also be considered. Vaughan's theory, normalization of
      deviance, is one systemic theory that can account for quotation error.
      Application Quotation error is occurring in human factors and should receive more
      attention. According to Vaughan's theory, the normal everyday systems that
      promote scholarship may also allow mistakes, mishaps, and quotation error to
      occur.

PMID- 29328782
TI  - The role of nivolumab in melanoma.
AB  - The incidence of melanoma continues to rise worldwide. Prior to 2010, there had
      been no progress in the treatment of advanced melanoma in living memory. Since
      then, immunotherapy has become a standard of care in the treatment of advanced
      melanoma. Nivolumab is a fully human monoclonal antibody against PD-1, which is a
      negative regulatory checkpoint in the T cells. The clinical benefit of nivolumab
      as a single agent is well established, with response rates of >=40%, durable
      responses and a favorable tolerability profile. The combination of nivolumab and
      ipilimumab has also become a standard of care and the role of nivolumab in the
      adjuvant setting for high-risk patients has been recently confirmed.

PMID- 29328785
TI  - Immune Responses in the Liver.
AB  - The liver is a key, frontline immune tissue. Ideally positioned to detect
      pathogens entering the body via the gut, the liver appears designed to detect,
      capture, and clear bacteria, viruses, and macromolecules. Containing the largest
      collection of phagocytic cells in the body, this organ is an important barrier
      between us and the outside world. Importantly, as portal blood also transports a
      large number of foreign but harmless molecules (e.g., food antigens), the liver's
      default immune status is anti-inflammatory or immunotolerant; however, under
      appropriate conditions, the liver is able to mount a rapid and robust immune
      response. This balance between immunity and tolerance is essential to liver
      function. Excessive inflammation in the absence of infection leads to sterile
      liver injury, tissue damage, and remodeling; insufficient immunity allows for
      chronic infection and cancer. Dynamic interactions between the numerous
      populations of immune cells in the liver are key to maintaining this balance and
      overall tissue health.

PMID- 29328786
TI  - Connections Between Metabolism and Epigenetics in Programming Cellular
      Differentiation.
AB  - Researchers are intensifying efforts to understand the mechanisms by which
      changes in metabolic states influence differentiation programs. An emerging
      objective is to define how fluctuations in metabolites influence the epigenetic
      states that contribute to differentiation programs. This is because metabolites
      such as S-adenosylmethionine, acetyl-CoA, alpha-ketoglutarate, 2
      hydroxyglutarate, and butyrate are donors, substrates, cofactors, and antagonists
      for the activities of epigenetic-modifying complexes and for epigenetic
      modifications. We discuss this topic from the perspective of specialized CD4+ T
      cells as well as effector and memory T cell differentiation programs. We also
      highlight findings from embryonic stem cells that give mechanistic insight into
      how nutrients processed through pathways such as glycolysis, glutaminolysis, and
      one-carbon metabolism regulate metabolite levels to influence epigenetic events
      and discuss similar mechanistic principles in T cells. Finally, we highlight how
      dysregulated environments, such as the tumor microenvironment, might alter
      programming events.

PMID- 29328784
TI  - DNA-Encoded Chemical Libraries: A Selection System Based on Endowing Organic
      Compounds with Amplifiable Information.
AB  - The discovery of organic ligands that bind specifically to proteins is a central
      problem in chemistry, biology, and the biomedical sciences. The encoding of
      individual organic molecules with distinctive DNA tags, serving as amplifiable
      identification bar codes, allows the construction and screening of combinatorial
      libraries of unprecedented size, thus facilitating the discovery of ligands to
      many different protein targets. Fundamentally, one links powers of genetics and
      chemical synthesis. After the initial description of DNA-encoded chemical
      libraries in 1992, several experimental embodiments of the technology have been
      reduced to practice. This review provides a historical account of important
      milestones in the development of DNA-encoded chemical libraries, a survey of
      relevant ongoing research activities, and a glimpse into the future.

PMID- 29328787
TI  - Immune Responses to Retroviruses.
AB  - Retroviruses are genome invaders that have shared a long history of coevolution
      with vertebrates and their immune system. Found endogenously in genomes as traces
      of past invasions, retroviruses are also considerable threats to human health
      when they exist as exogenous viruses such as HIV. The immune response to
      retroviruses is engaged by germline-encoded sensors of innate immunity that
      recognize viral components and damage induced by the infection. This response
      develops with the induction of antiviral effectors and launching of the clonal
      adaptive immune response, which can contribute to protective immunity. However,
      retroviruses efficiently evade the immune response, owing to their rapid
      evolution. The failure of specialized immune cells to respond, a form of neglect,
      may also contribute to inadequate antiretroviral immune responses. Here, we
      discuss the mechanisms by which immune responses to retroviruses are mounted at
      the molecular, cellular, and organismal levels. We also discuss how intrinsic,
      innate, and adaptive immunity may cooperate or conflict during the generation of
      immune responses.

PMID- 29328783
TI  - Signaling to and from the RNA Polymerase III Transcription and Processing
      Machinery.
AB  - RNA polymerase (Pol) III has a specialized role in transcribing the most abundant
      RNAs in eukaryotic cells, transfer RNAs (tRNAs), along with other ubiquitous
      small noncoding RNAs, many of which have functions related to the ribosome and
      protein synthesis. The high energetic cost of producing these RNAs and their
      central role in protein synthesis underlie the robust regulation of Pol III
      transcription in response to nutrients and stress by growth regulatory pathways.
      Downstream of Pol III, signaling impacts posttranscriptional processes affecting
      tRNA function in translation and tRNA cleavage into smaller fragments that are
      increasingly attributed with novel cellular activities. In this review, we
      consider how nutrients and stress control Pol III transcription via its factors
      and its negative regulator, Maf1. We highlight recent work showing that the
      composition of the tRNA population and the function of individual tRNAs is
      dynamically controlled and that unrestrained Pol III transcription can reprogram
      central metabolic pathways.

PMID- 29328789
TI  - From working hours' restrictions to professional identity: The development of the
      surgical care practitioner role.
AB  - This article describes how restrictions to working hours have encouraged the
      expansion of the surgical care practitioner role. It also discusses how this role
      has evolved and the identity that has been formed in the context of
      interprofessional surgical education.

PMID- 29328788
TI  - The role of elastomeric pumps in postoperative analgesia in orthopaedics and
      factors affecting their flow rate.
AB  - Elastomeric pumps are mechanical devices composed of an elastomeric balloon
      reservoir into which the drug to be infused is stored, a protective casing (used
      by some manufacturers), a flow controller and a wound catheter. In orthopaedics
      they are used to provide continuous local infiltration analgesia. In this way
      patients rely less on other routes of analgesia and thus avoid their systemic
      side effects. Studies have shown good response to analgesia with these pumps for
      the first 24 hours but their benefit is not as clear at 48 and 72 hours. There
      are numerous factors that affect the flow rate of elastomeric pumps. Some are
      inherent to all elastomeric pumps such as: the pressure exerted by the
      elastomeric balloon, catheter size, the vertical height of the pump in relation
      to the wound, viscosity and partial filling. There are also other factors which
      vary according to the manufacturer such as: the optimal temperature to obtain the
      desired flow rate as this directly affects viscosity, the dialysate that the
      analgesic drug is mixed with (ie normal saline or 5% dextrose), and the storage
      conditions of the fluid to be infused. It is thus essential to follow the
      clinical guidelines provided by the manufacturer in order to obtain the desired
      flow rate.

PMID- 29328790
TI  - Hospital stay and blood transfusion in elderly patients with hip fractures.
AB  - Neck of femur (NOF) fractures in elderly patients are the most frequent condition
      which an orthopaedic surgeon confronts nowadays. The incidence of these fractures
      is increasing as the population continues to age. These patients absorb the
      majority of the resources in the hospitals, as their healthcare demands are
      increased. This study included all patients who were admitted to our hospital
      between January and October 2015 following a neck of femur fracture. A total of
      336 patients were included (72.3% female). We gathered demographic and
      hospitalisation data from patients' files. Haemoglobin (Hb) levels at admission
      and transfusion data were also collected. Male patients appeared to have a
      relatively higher risk of mortality than females (p=0.01). Patients with high ASA
      grade (IV) had a higher mortality rate (p=0.01). Age, delay of surgery, type of
      surgery, AMTS and Hb at admission and type of fracture on the other hand did not
      have a significant impact on mortality (p>0.05). Patients who needed transfusion
      during their hospitalisation had significantly lower Hb at admission (p=0.044).
      More specifically, patients who had Hb<110 at admission were more likely to need
      transfusion (p<0.001). Hospitalisation of patients who needed transfusion was
      significantly prolonged. In our effort to deliver the best services to our
      patients, this study considers transfusing the elderly patients with low Hb at
      admission (Hb<110) pre-operatively, with a view to increasing their reserves for
      the operation and potentially speeding up the rehabilitation process and
      decreasing their hospitalisation time.

PMID- 29328791
TI  - How noisy are total knee and hip replacements?
AB  - Orthopaedic theatre can be noisy. Fifty percent of orthopaedic theatre staff have
      features of noise-induced hearing loss (NIHL). In this study, decibel (dB) levels
      were recorded in 17 total knee replacements (TKRs) and 11 total hip replacements
      (THRs). Noise levels reached 105.6dB(A) using a hammer and 97.9dB(A) with an
      oscillating saw. Exposure to levels above 90dB (which occurred in every case)
      even for short time periods is proven to cause irreversible loss of hearing.
      Tools used in orthopaedic theatre produce impulse noises that can cause NIHL.
      Further investigation is required.

PMID- 29328792
TI  - Identification and management of nontraumatic splenic rupture.
AB  - A 43-year old previously fit and well gentleman presented to the emergency
      department (ED) with a two day history of worsening epigastric pain. He had had
      coryzal symptoms the preceding week but had no other past medical history. He was
      haemodynamically stable at presentation and an ultrasound scan (US) performed in
      the ED could not definitively rule out intra-abdominal fluid. In view of his
      tender abdomen on examination and a haemoglobin level of 9.2g/dL, a computerised
      tomography (CT) scan was performed and revealed extensive high-density fluid
      within the peritoneal cavity, raising the possibility of a concealed bleed but no
      obvious source was identified by the scan.

PMID- 29328793
TI  - Novel Molecular and Phenotypic Insights into Congenital Lung Malformations.
AB  - RATIONALE: Disruption of normal pulmonary development is a leading cause of
      morbidity and mortality in infants. Congenital lung malformations are a unique
      model to study the molecular pathogenesis of isolated structural birth defects,
      as they are often surgically resected. OBJECTIVES: To provide insight into the
      molecular pathogenesis of congenital lung malformations through analysis of cell
      type and gene expression changes in these lesions. METHODS: Clinical data, and
      lung tissue for DNA, RNA, and histology, were obtained from 58 infants undergoing
      surgical resection of a congenital lung lesion. Transcriptome-wide gene
      expression analysis was performed on paired affected and unaffected samples from
      a subset of infants (n = 14). A three-dimensional organoid culture model was used
      to assess isolated congenital lung malformation epithelium (n = 3). MEASUREMENTS
      AND MAIN RESULTS: Congenital lung lesions express higher levels of airway
      epithelial related genes, and dysregulated expression of genes related to the Ras
      and PI3K-AKT-mTOR (phosphatidylinositol 3-kinase-AKT-mammalian target of
      rapamycin) signaling pathways. Immunofluorescence confirmed differentiated airway
      epithelial cell types throughout all major subtypes of congenital lung lesions,
      and three-dimensional cell culture demonstrated a cell-autonomous defect in the
      epithelium of these lesions. CONCLUSIONS: This study provides the first
      comprehensive analysis of the congenital lung malformation transcriptome and
      suggests that disruptions in Ras or PI3K-AKT-mTOR signaling may contribute to the
      pathology through an epithelial cell-autonomous defect.

PMID- 29328794
TI  - Corneal abrasion following anaesthesia for non-ocular surgical procedures: A case
      controlled study.
AB  - The aim of this study was to identify risk factors associated with perioperative
      corneal abrasion at a single hospital in Mineola, New York (United States). A
      chart review was conducted of patients with perioperative corneal abrasion
      following non-ocular surgery and age-matched controls between June 2011 and
      November 2013. An age-stratified logistic regression model evaluated the
      association between corneal abrasion and potentially predisposing variables. The
      adjusted odds of a corneal abrasion occurring were 4.6 times greater for patients
      having surgery for >= 3 hours (p=0.001) and 3.6 times greater for patients with
      pre-existing ocular disease (p=0.02). Gender, diabetes status, surgical procedure
      or position were not found to be associated with the occurrence of a corneal
      abrasion. Corneal abrasions were associated with longer procedures and history of
      pre-existing ocular disease. No significant association between body positioning
      or surgical site and perioperative corneal abrasion was found. The study
      concludes that a longer duration of surgical procedure and pre-existing ocular
      disease are risk factors for perioperative corneal abrasion.

PMID- 29328795
TI  - Emerging/changing fashion trends and their impact on conduct of anaesthesia.
AB  - One of the innate features of human behaviour is to enhance personal image in
      order to look different from the rest of the crowd and to satisfy a need for
      individualism. People use different dress codes, body makeup and artificial
      gadgets to improve their personal and physical appearance. The main motive behind
      all these efforts is personal satisfaction, to appear attractive to others and to
      overcome phobias and complexes.

PMID- 29328796
TI  - eAppendicitis: Diagnostic uncertainty in appendicitis and the role of ehealth -
      does IT help?
AB  - The availability of medical information on the World Wide Web has grown as
      information technology has become more accessible. Patients seeking online
      information may be able to selfselect conditions having been adequately informed.
      This study evaluates the effect of eHealth information on those presenting to
      hospital with a suspected appendicitis and its effect on their management and
      clinical outcome. Patients who had performed online reading were more likely to
      go to theatre but were less likely to have a confirmed histological diagnosis of
      appendicitis.

PMID- 29328797
TI  - Does a dedicated orthopaedic day surgery list improve delivery of trauma
      services?
AB  - Our aim was to implement a 23-hour pathway for uncomplicated trauma to overcome
      delays and improve efficiency. A retrospective review of a single surgeon series
      of 105 consecutive patients operated on between July 2010 and July 2011 was
      performed. With recently revised trauma tariffs, we believe an efficient day
      surgery trauma list improves theatre utilisation, reduces inpatient bed demands,
      prioritises major and sub-specialist trauma and delivers patient satisfaction.

PMID- 29328798
TI  - The early days of surgery for cardiac injuries.
AB  - Over many centuries, wounds of the heart were thought to be fatal. With the
      introduction of first anaesthesia and then antiseptic surgery in the second half
      of the 19th century, there was an explosion in surgery; the abdominal cavity, the
      chest, the skull were explored and operated upon and yet the heart was considered
      to be a 'no go' region of the body. One of the greatest and most innovative
      surgeons of that time, Theodor Billroth of Vienna, who must be considered one of
      the fathers of modern surgery, with pioneering work on many parts of the body,
      wrote: 'The surgeon who attempts to suture a wound of the heart should lose the
      respect of his colleagues'.

PMID- 29328800
TI  - The human element of giving and receiving feedback.
AB  - Human factors is the scientific subject that concerns the understanding of
      interactions amongst humans, it is what affects behaviour and performance in the
      work place (Ives and Hillier 2015), particularly in high risk areas such as the
      aviation industry and healthcare. In this opinion piece it will be limited to the
      healthcare profession.

PMID- 29328799
TI  - Clinical supervision: beyond the first flush.
AB  - Nearly two decades ago, Smith (1999) recognised that little had been published on
      the implementation and usefulness of clinical supervision in the operating
      theatre. Accordingly, she conducted a small action research project and reported
      its findings. These were deemed to have been in a positive direction and a number
      of benefits were listed, essentially clustered around better communication
      between operating department practitioners (ODPs). Prophetically, however, she
      thought 'it would be interesting to observe if this enthusiasm and motivation
      continues after the project is completed' (p308). Two years later, Smith (2001)
      lamented that clinical supervision was no longer practised in theatres and that
      its introduction in other areas had 'met with little success' (p436). She
      believed the reasons to be the 'culture of the NHS, the negative attitudes by
      enough members of staff to have an impact and hidden agendas and micro-politics'.

PMID- 29328801
TI  - Preceptorship for practitioners new to theatre departments.
AB  - The aim of this study was to identify the influences and constraints of a
      preceptorship programme for perioperative practitioners and to assess the
      potential impact on the learning process. The programme takes into account the
      values of the NHS trust for which I work: to care about our patients, quality,
      the future, serving local people, improvement and being stronger together. This
      foundation NHS trust has a vision for the future that puts the patient at the
      heart of everything it does and is guided by the principles and values about
      which the people care deeply.

PMID- 29328802
TI  - Case study: Laparoscopic appendicectomy requirements and human factors
      surrounding emergency care.
AB  - The purpose of this case study is to inform practitioners of the requirements for
      non-scheduled surgery and the legal, professional and ethical issues surrounding
      emergencies. Areas for learning include the surgical requirements for
      appendectomy, evaluation of the differences between scheduled and unscheduled
      care, and consideration of the vital role that human factors play in emergency
      situations.

PMID- 29328803
TI  - Parent pagers: Improving patient experience and efficiency in paediatric PACU.
AB  - A quality improvement initiative undertaken by the paediatric recovery team at
      the Leeds Children's Hospital sought to improve patient experience and efficiency
      by implementing an electronic pager system to contact parents/carers following
      their child's surgery.

PMID- 29328804
TI  - Replacement of the nose.
AB  - Today's reconstructive surgeons may not be aware that replacement of the nose was
      carried out successfully as long ago as the 16th century by the surgeon Gaspar
      Taliacozzo of Bologna, Italy, who published a detailed and illustrated account of
      his operation in 1597. This procedure comprised raising a flap of skin from the
      upper arm to reconstruct the nose. The arm was kept in place, with the hand
      resting on the patient's head, using elaborate splinting until adherence had
      taken place; the flap was then detached from the donor arm. The operation was
      seldom used following this success, surgeons relying on replacement of the lost
      nose with an artificial organ fashioned from wood or silver and strapped over the
      defect.

PMID- 29328805
TI  - Recent Advances in the Application of Cold Plasma Technology in Foods.
AB  - The past decade has seen a surge in the scientific literature investigating the
      potential food-related applications of plasma. A multidisciplinary scientific
      effort has started to demonstrate process efficacy for a range of plasma
      applications, including antimicrobial, pesticidal, food functionalization, and
      waste treatment. Insights into the interactions of plasma species with food and
      the mechanisms of action are also emerging. This review examines the current
      status of cold plasma technology within the food sector with a particular
      emphasis on emerging applications. Opportunities and current challenges that need
      to be addressed for successful adoption of the approach by industry are detailed.

PMID- 29328806
TI  - Tailoring Delivery System Functionality Using Microfluidics.
AB  - Various methods are currently used by the food industry to investigate and
      prepare emulsions, encapsulates, and other structures. However, these techniques
      do not allow accurate control over processing variables, which can negatively
      impact the resultant product properties. In this context, microfluidic technology
      has been proposed as a powerful tool for the development of innovative food
      structures, given its use of small amounts of fluids and high reproducibility,
      resulting in monodisperse droplets and particles. These benefits prove useful
      when a researcher is interested in investigating the fundamental effects of
      specific variables while keeping the others under precise control. This review
      presents an overview of the use of microfluidic devices as technological tools
      for the preparation of innovative food products and discusses their potential for
      the development of tailored delivery systems.

PMID- 29328807
TI  - Conversion of Agricultural Streams and Food-Processing By-Products to Value-Added
      Compounds Using Filamentous Fungi.
AB  - The design of new food products and increased agricultural activities have
      produced a diversity of waste streams or by-products that contain a high load of
      organic matter. The underutilization of these streams presents a serious threat
      to the environment and to the financial viability of the agricultural sector and
      the food industry. Oleaginous microorganisms, such as yeast and microalgae, have
      been used to convert the organic matter present in many agricultural waste
      streams into an oil-rich biomass. Filamentous fungi are promising oleaginous
      microorganisms because of their high lipid accumulation potential and simple
      biomass recovery, the latter being related to their pellet-like growth morphology
      in submerged cultivation. This review highlights the use of oleaginous
      filamentous fungi to convert food by-products into value-added components,
      including the effect of cultivation conditions on biomass yield and composition.
      Special attention is given to downstream processing for the commercial production
      of fungal oil. Also discussed are innovative techniques to optimize the biomass
      oil yield and to minimize the challenges associated with biomass harvesting and
      oil extraction at industrial scale.

PMID- 29328808
TI  - Effective Prevention of Oxidative Deterioration of Fish Oil: Focus on Flavor
      Deterioration.
AB  - Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), both abundant in fish
      oil, are known to have significant biochemical and physiological effects
      primarily linked to the improvement of human health, especially cardiovascular
      and brain health. However, the incorporation of fish oil into foods and beverages
      is often challenging, as fish oil is very easily oxidized and can cause
      undesirable flavors. This review discusses this rapid formation of the fishy and
      metallic off-flavors, focusing especially on an early stage of fish oil
      oxidation. Although oxidative stability and quality of commercialized fish oil
      have improved over the past few years, there is a still a problem with its
      application: Flavor deterioration can be found even at very low oxidation levels.
      This review also notes the effective way to inhibit the formation of the volatile
      compounds responsible for the flavor deterioration.

PMID- 29328809
TI  - Methods for the Control of Foodborne Pathogens in Low-Moisture Foods.
AB  - Low-moisture foods (LMFs) have been defined as those food products with a water
      activity (aw) less than 0.85 and are generally considered less susceptible to
      microbial spoilage and the growth of foodborne pathogens. However, in recent
      years, outbreaks linked to LMFs have increased, with Salmonella spp., Bacillus
      cereus, Cronobacter sakazakii, Clostridium spp., Escherichia coli O157:H7, non
      O157 E. coli, and Staphylococcus aureus being the principal pathogens involved.
      Because of the new concerns raised as a result of recent outbreaks, new
      approaches need to be developed to control foodborne pathogens in LMFs. This
      review summarizes the recent research on novel inactivation methods suitable for
      use on LMFs. Among the methods discussed are the nonthermal inactivation methods
      as well as other novel methods such as radio-frequency and microwave heating.
      Additional research is needed to evaluate older technologies and develop new
      technologies, either alone or in combination, to understand the mechanisms of
      inactivation.

PMID- 29328810
TI  - Shelf Life of Food Products: From Open Labeling to Real-Time Measurements.
AB  - The labels currently used on food and beverage products only provide consumers
      with a rough guide to their expected shelf lives because they assume that a
      product only experiences a limited range of predefined handling and storage
      conditions. These static labels do not take into consideration conditions that
      might shorten a product's shelf life (such as temperature abuse), which can lead
      to problems associated with food safety and waste. Advances in shelf-life
      estimation have the potential to improve the safety, reliability, and
      sustainability of the food supply. Selection of appropriate kinetic models and
      data-analysis techniques is essential to predict shelf life, to account for
      variability in environmental conditions, and to allow real-time monitoring. Novel
      analytical tools to determine safety and quality attributes in situ coupled with
      modern tracking technologies and appropriate predictive tools have the potential
      to provide accurate estimations of the remaining shelf life of a food product in
      real time. This review summarizes the necessary steps to attain a transition from
      open labeling to real-time shelf-life measurements.

PMID- 29328811
TI  - The healthcare team's perception of the role of the perioperative nurse: A
      qualitative study.
AB  - The surgical process requires the coordination of a number of professionals who
      understand their own roles and responsibilities, as well as those of the team. In
      the perioperative setting, expectations are established around behaviors and
      competencies of every team member. These expectations are influenced by
      knowledge, training and experience, and may ultimately influence results and the
      ability to adapt and respond to work demands. In Chile, there exists an ambiguity
      and lack of definition in the role of the nurse. The objective of this study was
      to examine the healthcare team's perception of the current role of the
      perioperative nurse, as well as the expected and desired characteristics of the
      role from the team's perspective. A qualitative, descriptive case study was
      carried out, using semi-structured interviews conducted with a purposive sample
      of surgeons, anaesthesiologists, professional nurses and technical nurses from
      three hospitals in Santiago, Chile. The accounts were analysed using an
      inductive, thematic format. It was found that the current perioperative nursing
      role, with a predominance of administrative charting, recordkeeping and
      guidelines for the management of safety, quality control and human and material
      resources, restricts direct patient care. Expected characteristics of the role
      included comprehensive theoretical and practical training and the development of
      relational skills for teamwork, direct patient care and advocacy in the surgical
      context. These results provided initial steps towards redefining the role of the
      perioperative nurse, strengthening collaborative efforts and optimising patient
      care during a time of high vulnerability.

PMID- 29328812
TI  - Airway management of the morbidly obese patient.
AB  - A UK study found that obese patients are twice as likely as non-obese patients to
      develop airway problems during general anaesthesia (Cook et al 2011). This
      article focuses on airway management of morbidly obese patients during
      anaesthesia and examines the associated respiratory, gastric, and existing co
      morbidity complications that can be expected. Strategies that practitioners can
      use to reduce these risks are discussed.

PMID- 29328813
TI  - The perfect surgical assistant: Calm, confident, competent and courageous.
AB  - Poor surgical assistance has been identified as a major stressor in surgeons,
      making the ability to provide effective surgical assistance an important skill
      which will have a lifelong impact on the surgical patient. Knowledge and
      technical ability are clearly important, but strong personal qualities are more
      so in the long run. This applies to all who provide assistance either as a
      surgical first assistant or surgical care practitioner. These skills and
      attributes are needed to provide a safe service that meets the expectations of
      both the professional regulatory authorities and surgical Royal Colleges. Advice
      is given in this article as to how non-medical practitioners may acquire these
      skills.

PMID- 29328814
TI  - Pharyngotomy for a swallowed denture.
AB  - The introduction of inhalation anaesthesia, first by the use of ether in 1845 and
      then of chloroform in the following year, saw an explosion in the range and
      extent of major surgical procedures as patients were spared the agonies of the
      surgeon's knife. A good example of this was the operation of pharyngotomy -
      opening the cervical oesophagus through a lateral incision of the neck - to
      remove an impacted foreign body. One cannot imagine a surgeon being able to do
      this without the benefit of an anaesthetic! Edward Cock, a surgeon at Guy's
      Hospital, performed this operation successfully on two occasions; the second was
      reported in detail in the Guy's Hospital Reports 1868, Volume 28.

PMID- 29328815
TI  - Review of the correlation between hospice philosophies and logos.
AB  - A review was undertaken of the ability of some published hospice philosophies and
      logos from different countries, known to the author, to convey the spirit of
      hospice care. Weisman's (1988) essential criteria for a hospice programme - which
      acknowledge the patient, family and staff - were used when comparing the
      comprehensive nature of both philosophies and logos. The findings suggest that
      symbolic logos show a greater potential to succinctly convey the comprehensive
      spirit of hospice care than written philosophies.

PMID- 29328816
TI  - Building the pyramids: palliative care patients' perceptions of making art.
AB  - Throughout history artists have spoken of the inherent value of art to humanity.
      This paper describes a study which was undertaken to ascertain the value of
      making sculpture, as opposed to diversional activity, for people with advanced
      cancer. Day-patients at a palliative care centre were invited to participate in
      the making of a sculpture and their reactions were gathered via semi-structured
      interviews. From the qualitative data generated it is apparent that the activity
      was valuable to the participants for a variety of reasons. The metaphor of
      'building the pyramids', supplied by a patient, to describe the art-making,
      provided a useful framework in which to explore the patients' reasons for valuing
      the activity. Notions of scale, ambition, achievement, longevity and
      transcendence were also recorded.

PMID- 29328817
TI  - Cancer Nursing: Creating the Future 9th International Conference on Cancer
      Nursing, August 12-15 1996.
AB  - During the weekend of 10-12 August 1996 over 1400 cancer nurses from over 70
      countries began to converge on Brighton, England, the venue for the 9th biennial
      conference. It was hosted jointly by The Royal Marsden NHS Trust and the Royal
      College of Cancer Nursing Society, under the auspices of The International
      Society of Nurses in Cancer Care. The conference venue was the Metropole Hotel
      and the organisation of the event was in the capable hands of the RCN conference
      Unit.

PMID- 29328818
TI  - Does aromatherapy provide an holistic approach to palliative care?
AB  - Palliative care specialist nurses aim to ensure that clients are offered the full
      range of care modalities. It is important that care is given to the total person.
      This paper will critically analyse the role of complementary therapy as a
      contribution to palliative care. Aromatherapy will be specifically highlighted,
      including examination of the way in which it relates to the four main principles
      of holism.

PMID- 29328819
TI  - Launch of RCN Cancer Nursing Society Reports.
AB  - Unquestionably, people affected by cancer should have access to nurses with
      appropriate experience and expertise if they are to receive the best possible
      care. This message, which became a recurring theme during the 9th International
      Conference on Cancer Nursing is central to two timely RCN Cancer Nursing society
      reports, which were formally launched at the society's reception held during the
      week of the conference.

PMID- 29328820
TI  - Fatigue in patients receiving chemotherapy for advanced cancer.
AB  - Severe and unremitting fatigue is a common symptom in individuals with advanced
      disease. Combined with weakness it comprises a syndrome known as asthenia.
      Asthenia is associated with advanced cancer, and becomes an increasing problem
      for patients as their disease progresses, having enormous implications for
      quality of life. However, despite its prevalence and impact, relatively little is
      known about this complex syndrome. The study described in this paper investigated
      and compared the fatigue experienced by cancer patients with different stages of
      disease, who were receiving chemotherapy. The results from this study both
      support the notion that fatigue increases as cancer progresses, and provide
      evidence for the prevalence of asthenia.

PMID- 29328821
TI  - Special interest session on C-PET.
AB  - C-PET, a tool designed to aid communication between health care professionals and
      women with advanced breast cancer, was launched at a special interest session of
      the International Conference on Cancer Nursing, held in Brighton in August.

PMID- 29328822
TI  - Ethics of resource distribution: implications for palliative care services.
AB  - Over the past few years changes in health care delivery worldwide have prompted
      health care professionals to become increasingly aware of, and involved in,
      decisions surrounding resource distribution. This paper aims to examine the
      ethical issues behind such decisions with particular reference to palliative care
      services. It is suggested that current outcome measures used to examine the
      quality and effectiveness of care are unsuitable for use within the palliative
      care setting, and that health care professionals within the field should be aware
      of, and promote the use of, more appropriate outcome measures. This is essential
      in order that the philosophy central to palliative care may be upheld and
      resources maintained at an appropriate level.

PMID- 29328823
TI  - Improving psychosocial care: a professional development programme.
AB  - Despite the numerous reports of difficulties experienced by health care providers
      in providing psychosocial care to terminally ill patients and their families, few
      studies have yet been undertaken to examine the effectiveness of different
      educational approaches to addressing these issues. The aim of this paper is to
      describe a programme of professional development for palliative care nurses,
      which is currently being offered to 181 registered nurses in Queensland,
      Australia. The programme is based on an action learning model and is designed to
      facilitate processes of reflection and peer consultation. In Part One of this
      paper, a review of this literature is presented to provide the background and
      rationale for the programme design. Details of the research programme developed
      to evaluate the programme will be presented in Part Two of this paper, which is
      to be published in the next issue of this Journal.

PMID- 29328825
TI  - International perspectives: current enthusiasm and future potential.
AB  - This summer has had a distinctly international flavour from my point of view.
      With the 9th International Conference on Cancer Nursing based in England, nurses
      from around the world began converging on London weeks, and even months ahead of
      time, in order to combine a holiday with visits to cancer and palliative care
      services in the United Kingdom (UK).

PMID- 29328826
TI  - Evidence-based practice: meeting a need within palliative nursing.
AB  - Palliative care has progressed dramatically in terms of sound evidence-based
      practice since its inception in the mid 1970s. Far from being a negative
      judgemental statement this is intended as a historical statement of fact,
      recognising that without pioneers such as Dame Cicely Saunders within the hospice
      movement, we would not have a basis from which to evolve and improve palliative
      care.

PMID- 29328827
TI  - Developing a symptom distress scale for terminal malignant disease.
AB  - Symptom control is an important component of palliative care. The degree of
      distress caused by symptoms is individual. Instruments to measure symptom
      distress in patients with cancer have been developed, but have been poorly
      validated in the terminally ill. This study was an exploratory, descriptive,
      cross-sectional survey of 49 dying cancer patients, 60 professional carers
      (doctors and nurses) and 30 bereaved relatives. Semi-structured interviews were
      used to identify distressing symptoms for the dying cancer patient. The results
      indicated a diversity in the symptom experience and were used in the development
      of a physical symptom distress scale. Items were selected from a pool of symptoms
      generated from the three data sources, and compared with the literature of
      symptom distress in general cancer patients and symptom prevalence studies in
      terminal care. These were then compared with existing symptom distress scales. An
      adaptation of the physical sub-scale of the Rotterdam Symptom Checklist is
      proposed.

PMID- 29328828
TI  - Monitoring pressure sores in a palliative care setting.
AB  - Pressure sore prevention and management represents a major challenge to
      palliative care nurses. The balance of promoting comfort, providing appropriate
      care and following patient wishes can lead to dilemmas in decision making. This
      prospective study set out to gather more in-depth information on the extent and
      nature of the problem of pressure sores within a hospice. Areas investigated
      included prevalence and incidence rates, site and stage of sores and associated
      pain. Assessment using the Waterlow at risk score demonstrated that the majority
      of patients were within the high or very high risk category. The results have
      been used to inform practice, influence resource decisions and set a benchmark
      for future monitoring.

PMID- 29328829
TI  - The effect of sudden sibling loss on the adolescent or young adult.
AB  - Most research on sibling loss has concentrated on the effect of sibling loss in
      early childhood, but little is known about how the sudden death of a sibling
      affects the late adolescent or young adult. Although there are no definite
      boundaries to define adolescence or young adulthood, for the purpose of this
      article, it occurs between sixteen and thirty years of age. This paper is a
      review of the literature on such a loss and examines how adolescents grieve and
      the effect of family dynamics before and after the death and attempts to indicate
      ways in which adolescents can be helped at such a time.

PMID- 29328830
TI  - Letters.
AB  - Calculating opioid dose Nursing on the net.

PMID- 29328831
TI  - Patient autonomy and cancer treatment decisions.
AB  - Informing cancer patients about their diagnosis, prognosis and treatment options
      continues to create controversy, conflict and confusion amongst health care
      professionals. In suggesting that autonomous patients choose to be involved in
      treatment decisions, and share the ultimate responsibility for the out-come,
      Randall and Downie (1996) over simplify a complex ethical dilemma. The fragility
      of 'autonomy' as a concept, renders it vulnerable to individual circumstances,
      willingness to share responsibility and the ability of clinicians to release
      control. Ethical decision making models are systematic arrangements of standards
      designed to motivate and guide actions. Seedhouse and Lovett (1992) presented an
      ethical grid as a means by which a clinician might be guided through complex
      ethical dilemmas. The ethical grid has been utilised in an attempt to examine the
      issue of patient autonomy and cancer treatment decisions.

PMID- 29328832
TI  - The development of holistic dependency criteria for a specialist palliative care
      service.
AB  - This paper offers an overview of the development of holistic dependency criteria
      for a specialist palliative care unit. These were developed through action
      research in order to respond to peaks and troughs of work load in a way that both
      contained staffing costs and provided high quality care. Separate criteria were
      developed for in-patient, day, community and lymphoedema services. These are
      actively used in day-to-day practice and long term planning to provide
      appropriate cost-efficient staffing. A broad framework has been developed for
      measuring dependency across clinical palliative care services. Each palliative
      care service would, however, need to develop its own criteria to take into
      account the nature of its particular patients.

PMID- 29328833
TI  - Staying ahead by moving forward.
AB  - The International Journal of Palliative Nursing was established in 1995. It is a
      peer reviewed Journal and has a strong international Editorial Board. The primary
      aims of the Journal are to disseminate research findings through the publication
      of academic papers, to explore the relationship between theory and practice and
      to stimulate the cross fertilisation of ideas between nurses involved in
      palliative care worldwide. The scope of the Journal reflects the development and
      expansion of the speciality of palliative care in general, and palliative nursing
      in particular. Consequently it carries papers which address the needs of people
      who are facing any life threatening illness, at any stage of the disease
      continuum, and who are cared for and supported in any care setting. The Journal
      is concerned with all aspects of palliative nursing practice, education,
      management and research. It endorses and values interprofessional working and
      welcomes papers and correspondence from all professional groups.

PMID- 29328834
TI  - Multidisciplinary case study as an approach to the evaluation of palliative care
      services: two example.
AB  - In this paper it is argued that there is a need to adopt a Abroad approach to the
      evaluation of palliative care services which: takes account of the differing
      interest groups; reflects the complexities of palliative care provision; and uses
      varied methods suited to the particular research question. The central tenets of
      the formative, qualitative model of evaluation are presented and the strengths of
      such an approach are illustrated by reference to the evaluation of two palliative
      care services.

PMID- 29328835
TI  - Functional health patterns applied to palliative care: a case study.
AB  - In all aspects of nursing appropriate care can only be delivered if patients'
      problems are appropriately identified. In palliative care assessment of need may
      be particularly difficult as patients experience such a wide range and complexity
      of problems. In this work Functional Health Patterns (FHP) were used to structure
      the assessment of a patient referred to as Maria. Once her needs were identified
      the data was verified and interpreted leading to nursing diagnoses. Case studies
      are a non-experimental approach in which a wealth of descriptive information is
      used to examine an issue in depth. In this paper a single case study design was
      used to apply FHP to identify the needs of Maria. In so doing the theoretical
      approach of FHP was applied in practice and was subjectively evaluated by an
      expert in the field of palliative care. The assessment outcomes are presented and
      may be of value to others wishing to review their patient assessment process.

PMID- 29328836
TI  - Nurses response to terminal care in the geriatric unit.
AB  - The elderly patient poses a major challenge in the future organisation of nursing
      services. Over half of all cancers occur in the elderly and account for a
      considerable proportion of diagnoses for patients in geriatric units. The aim of
      this exploratory study was to investigate the attitudes of nurses towards
      terminal care of patients on their wards. The questionnaire sought the opinions
      of nurses on acute and rehabilitation wards with regard to various aspects of
      terminal care. The study identified several areas where nurses on both acute and
      rehabilitation wards felt uncomfortable with their role in the care of such
      patients and areas where they felt to be lacking in certain skills. The study
      highlighted that although nurses considered care in these wards to be good, the
      provision of specialised training, and support of these nurses, would perhaps
      enable more satisfaction for the nurses and improve care of elderly patients
      during their terminal illness.

PMID- 29328837
TI  - Research based mouth care in palliative care patients in the community setting.
AB  - This article states the importance of research based mouth care for palliative
      care patients. Mouth care for palliative care patients has relied upon
      traditional nursing practice with little utilisation of research findings. The
      author has examined the literature in addition to surveying nursing practice and
      dental recommendations. The utilisation of an assessment tool is advocated
      enabling accurate assessment of mouth care needs for palliative care patients. A
      protocol and standard has been formulated and appears in Figures 2 and 3. These
      are designed to allow appropriate treatment to be given. The standard can be
      audited as appropriate to assess performance. The author intends to implement
      this change into her team of district nurses and monitor its effectiveness.

PMID- 29328838
TI  - Prophylactic amiodarone vs dronedarone for prevention of perioperative
      arrhythmias in offpump coronary artery bypass grafting: A pilot randomized
      controlled trial.
AB  - The aim of this study was to compare the effects of prophylactic dronedarone and
      amiodarone in prevention of arrhythmias during and following off-pump coronary
      artery bypass grafting (OPCAB). This randomized, controlled, double-blinded,
      parallel-group study was carried out on 36 adult male patients aged 30-70 years,
      with modified Parsonnet score 0-10 undergoing offpump coronary artery bypass
      grafting. After obtaining approval from the institutional ethics committee and
      informed consent, the patients were randomly allocated to two equal groups
      (n=18). In one group, patients were given inj. amiodarone 3mg/kg in 100ml of
      normal saline prior to skin incision intravenously over 20 minutes. In the second
      group patients received tablet dronedarone 400mg orally twice daily, commencing
      three days prior to the date of surgery. Patients in the amiodarone group
      received placebo tablet while patients in the dronedarone group received placebo
      infusion for the sake of blinding. The frequency and profile of arrhythmias
      intraoperatively and 24 hours postoperatively were studied. Intraoperative
      arrhythmias occurred in 50% of patients receiving amiodarone and 16.67% of
      patients receiving dronedarone. Maximum ventricular rate during atrial
      fibrillation was significantly lower in the dronedarone group (121 beats per min)
      than in the amiodarone group (168 beats per min). The study concludes that
      dronedarone appears to be at least as effective as amiodarone in prophylaxis of
      intraoperative and postoperative arrhythmias in patients undergoing OPCAB, with a
      better control of ventricular response.

PMID- 29328839
TI  - Challenges to the orthopaedic arthroplasty enhanced recovery programme.
AB  - We performed a retrospective study of patients undergoing total knee and hip
      arthroplasty on an enhanced recovery programme, to identify pre- and
      postoperative factors contributing to an increased length of hospital stay. Of
      109 patients, only 61 (56%) were ready for discharge on the fifth postoperative
      day. The three most common reasons for delays were oozing wounds, postoperative
      medical problems and failure to reach physiotherapy goals.

PMID- 29328840
TI  - Prolonged motor block following epidural anaesthesia: A proposed pathway for
      investigation and management to facilitate rapid MRI scanning to exclude
      vertebral canal haematoma.
AB  - Vertebral canal haematoma following epidural anaesthesia is a rare but
      potentially devastating occurence, which can lead to permanent neurological
      damage. Early clinical identification and diagnosis using MRI imaging with
      surgical decompression of the haematoma can lead to full recovery (Kebaish 2004).
      However surgical patients often have metal clips or staples, which are left
      inside the body, some of which are not MRI compatible. Currently there is no
      process to document which surgical clips have been used and their MRI
      compatibility in an accessible format. This can lead to a delay in performing MRI
      imaging. We propose a clinical pathway to expedite diagnosis of vertebral canal
      haematoma to incorporate a system to allow rapid identification of MRI
      compatibility of surgical clips used during surgery.

PMID- 29328841
TI  - Calculating drug infusion rates.
AB  - Intravenous drug administration is necessary for most patients who undergo
      general anaesthesia, and calculating correct dosages is essential, if those
      patients are to benefit from the proper therapeutic effects from their
      administered drugs, rather than suffering from any toxic effects which might
      result from overdosing.

PMID- 29328842
TI  - Case report of a patient with myasthenia gravis requiring a caesarean section.
AB  - RS is a 28-year old lady who presented in her first pregnancy to the High-Risk
      Obstetric Clinic for review in view of her medical history of myasthenia gravis.
      She was diagnosed with myasthenia gravis (MG) as a teenager, and underwent
      thymectomy soon after diagnosis. At the time of presentation to the clinic, RS
      was taking pyridostigmine and azathioprine for her MG.

PMID- 29328843
TI  - Gene and Cell Therapy in 2018: A Look Ahead.

PMID- 29328844
TI  - Cost awareness of disposable surgical equipment and strategies for improvement:
      cross sectional survey and literature review.
AB  - A significant healthcare funding gap has been predicted over the coming years.
      NHS England has made transparency and cost efficiency a key priority. Healthcare
      technology accounts for a large portion of healthcare expenditure. The aim of the
      study was to establish the cost awareness of theatre staff for disposable
      surgical equipment and to review the current evidence around improving cost
      awareness. A cross sectional survey was performed. A questionnaire was
      distributed to consultants, registrars, core surgical trainees and theatre scrub
      practitioners within an NHS foundation trust and analysed using Microsoft excel
      2010. Following the results, which indicated poor cost awareness amongst theatre
      staff, a literature review was performed to identify strategies to improving cost
      awareness in healthcare. The results showed that only 22% of all participants (n
      = 48) were able to estimate cost correctly. There was no significant difference
      in cost accuracy between surgeons or scrub practitioners. Strategies for
      improvement in cost awareness were identified. A lack of cost awareness was
      identified amongst theatre healthcare professionals for common disposable
      surgical equipment. This is an area which must improve through the use of proven
      strategies such as national programs, education, visible pricing and price
      feedback, as highlighted in this paper.

PMID- 29328845
TI  - Development and implementation of a theatre booking form and morning briefing
      meeting to improve emergency theatre efficiency.
AB  - The aim of this study was to improve emergency theatre efficiency via the
      introduction of a theatre booking form and morning briefing meeting. Process
      mapping was used to engage staff and consider if the emergency theatre may
      benefit from the application of a structured process of communication. A theatre
      booking form and morning briefing meeting were implemented to promote change.
      Efficiency was measured by theatre utilisation and characterised into neutral
      time, efficient time and inefficient time. The results demonstrated a 12.9%
      increase in efficient time, 3.3% fall in inefficient time and 9.6% fall in
      neutral time post-implementation, during the high volume work period of 08:00 to
      17:59 on weekdays. No improvement in efficiency was demonstrated outside these
      hours or on weekends during lower volume workloads. Utilisation of a theatre
      booking form and morning briefing meeting improved emergency theatre efficiency
      during high volume work periods by the application of a structured process of
      communication.

PMID- 29328846
TI  - A review of nausea and vomiting in the anaesthetic and post anaesthetic
      environment.
AB  - Postoperative nausea and vomiting (PONV) has long been known as a complication of
      anaesthesia and surgery. This paper focuses on the assessment of the risk factors
      related to PONV along with the strategies and interventions which can be put in
      place to manage the condition. The pharmacological and multi-modal treatment
      methods of managing the risk factors that contribute to PONV are discussed.

PMID- 29328847
TI  - An anaesthesia perspective on carotid body tumour (CBT) excision: A twenty-year
      case series at the Singapore General Hospital.
AB  - Carotid body tumours (CBT) are extremely rare neoplasms that arise from
      chemoreceptor cells at the bifurcation of the carotid artery. This rarity poses a
      challenge for the anaesthetist when dealing with surgeries for the removal of
      CBT. Reports of associated perioperative morbidity range from twenty to forty
      percent. This paper reviews the perioperative anaesthetic management of CBT
      patients and challenges in our institution's 20 year experience on 13 surgical
      CBT resections.

PMID- 29328849
TI  - Cultural issues in palliative care.
AB  - The understanding of different cultural needs is important in the field of
      palliative care. An individual's cultural background influences their way of
      behaviour and view of the world they live in. In Britain today, 5.5 per cent of
      the population comes from minority cultural groups. This paper argues that
      cultures in a plural society like Britain's are not static but continually
      changing. The nature of this change is discussed by looking at the processes of
      enculturation and acculturation. It is also argued that although some cultural
      change may take place, some basic rituals at death and dying remain unaffected.
      This then raises the need for health care professionals to be aware of the
      original (purist) value and belief system of each individual patient's culture,
      i.e. before acculturation, and keep that as a broad framework while assessing the
      current values and beliefs of that individual patient. The difference between
      culture and religion is briefly discussed, then a few cultural groups are
      selected to describe beliefs and practices during dying and at death. This is
      important because the basic tenet of palliative care is to view and treat the
      patient holistically. To do so, a clear understanding of the patient's values and
      belief system must be foremost.

PMID- 29328848
TI  - High risk endovascular aneurysm repair: a case report.
AB  - Mr AB is a 66-year old gentleman who presented for elective endovascular aneurysm
      repair (EVAR) following a routine screening scan identifying a 5.5cm abdominal
      aortic aneurysm (AAA). He had a past history of chronic obstructive pulmonary
      disease (COPD) with FEV1/FVC ratio of 48% on pre-assessment. He was hypertensive
      with a history of ischaemic heart disease (IHD), which has remained asymptomatic
      following coronary artery bypass grafting (CABG) eight years prior to this
      presentation.

PMID- 29328850
TI  - The concepts of truth telling and informed consent.
AB  - In the palliative care setting, nurses are regularly faced with the dilemma of
      what to tell their patients about the progress of their illness, treatment and
      their prognosis. This dilemma is not always handled in the best way and there are
      many difficulties for the nurse. This article examines the legal aspects of
      informed consent and highlights the dilemmas faced by nurses working in the
      palliative care field of nursing. This is an area which will remain controversial
      until open and clear guidance is given to carers on their roles and
      responsibilities. The objective of this article is to highlight the areas of
      difficulty where lack of clarity exist in order to provoke discussion on how
      these problems can be resolved.

PMID- 29328851
TI  - Experiential exercises in palliative care training.
AB  - Death education research has traditionally focused on the relative effectiveness
      of experiential versus didactic methods. Although experiential methods have been
      shown to be more effective at lowering death anxiety, little account has been
      taken of the distress that many people experience as a result of undertaking this
      kind of training. This article describes an investigation of the reactions of
      participants on a palliative care training course which included a day of
      experiential sessions. It was found that experiential training produced both
      positive outcomes, in terms of staff attitudes and clinical practice, and
      negative outcomes, in terms of emotional distress and anxiety experienced by
      participants. On balance, the positive aspects of this experiential training
      suggest that the gains do justify the means. Suggestions are therefore made for
      potential safeguards to minimise any adverse effects.

PMID- 29328852
TI  - Sexuality: the neglected component in palliative care.
AB  - Although sexuality is an integral part of holistic care, it appears to be an area
      that is seldom fully addressed or is even neglected entirely. The main reason
      appears to be nurses' discomfort with the issue of sexuality and a lack of nurse
      education in this area. This article advocates an eclectic model of care drawing
      on the work of several theorists. The ultimate aim is to look at the relevance
      and place of sexuality in the palliative care setting. A scenario identifies
      issues relating to sexuality in which this model was utilised.

PMID- 29328853
TI  - Palliative care services and settings: improving care.
AB  - The first part of this review focused on identifying studies which compared
      services and settings (O'Henley et al 1997). In the second part, the results of
      efforts to improve care in the areas previously identified as deficient are
      highlighted including communication, symptom control and support services. The
      guidelines that have been developed for palliative care are discussed along with
      the inherent difficulties faced by investigators when conducting research with
      the terminally ill. Nonetheless, more research is required to clarify which
      services work best for which kinds of patients and families in which
      circumstances.

PMID- 29328854
TI  - Leadership and management in specialist palliative care.
AB  - Since the publication in the UK of the White Paper 'Working for patients' (1989)
      which set out the Government's strategy for a better health service for patients,
      nursing management has undergone a metamorphosis. Senior nurse managers in newly
      established National Health Service Trusts have, in many cases, had to rise to
      the challenge of making the shift from a predominantly operational to a corporate
      role while maintaining their function as head of the profession of nursing
      without necessarily having management responsibility for nurses.

PMID- 29328855
TI  - Spiritual chaos: an alternative conceptualisation of grief.
AB  - Grief is examined in this article as spiritual chaos, rather than stages to be
      worked through. Major characteristics of grief and spirituality are identified as
      well as ways in which chaos theory can help us understand grief. Indigenous
      approaches to death, dying and grief are explored, and the role of the ritual
      elder, particularly in terms of creating a safe space in which grief can be
      safely sampled. Guidance from experienced helpers such as ritual elders assists
      persons experiencing grief to deal with issues in a more conscious way. It is
      argued that holistic health care teams require spiritual carers as full members,
      and that the role of spiritual carer may at times need to be undertaken by
      various members of the health care team.

PMID- 29328856
TI  - Clinical trials, palliative care and the research nurse.
AB  - This article describes the role of the research nurse in palliative care clinical
      trials. The need for these trials has been well documented, and there is a
      requirement to produce evidence that interventions employed in everyday practice
      actually work. This paper describes the explicit components and the multifaceted
      nature of the role of the research nurse in clinical trials in palliative care,
      and discusses the important part they can play in the advancement of this
      multidisciplinary specialty.

PMID- 29328857
TI  - Active palliative anti-cancer therapy.
AB  - Palliative care has a high profile in the delivery of cancer care services and is
      of growing interest to all health care practitioners. This reflects a marked
      change in attitudes to the management of cancer: not too long ago, nurses were
      forbidden to discuss treatment with patients, who were often ignorant of their
      diagnosis. Now, the focus has shifted to optimising quality of life in a
      comprehensive package of total care involving the patient and the family.

PMID- 29328858
TI  - Patient and professional centred care in the hospice.
AB  - Palliative nursing has an underpinning philosophy of caring for patients
      holistically and being patient centered. The essence of palliative nursing,
      however, may be compromised when nurses and other health care professionals fail
      to acknowledge and address their own care in an environment intense with loss,
      grief, pain and suffering. This paper explores how neglected anxieties and
      stress, coupled with factors of unconscious motivation, may jeopordise the
      excellence and expertise in hospice nursing and precipitate professional centred
      care. Recommendations include implementing and supporting initiatives such as
      reflection, clinical supervision and nurse debriefing.

PMID- 29328859
TI  - Effects of TENS applied to acupuncture points distal to a pain site.
AB  - The observation that patients with head and neck cancers undergoing radiotherapy
      continued to experience pain despite moderate analgesics prompted the first
      author to investigate whether transcutaneous electrical nerve stimulation (TENS),
      applied to acupuncture points away from the pain site, would increase the pain
      relief effect (Table 1). The pilot study involved four patients with head and
      neck cancers undergoing radiotherapy. The subsequent randomized trial involved 14
      patients undergoing inguinal herniorrhaphy. Pain relief in the group receiving
      TENS on true acupuncture points was compared with that in patients receiving TENS
      on non-true points. Pain relief was evaluated by pain score and morphine use in
      the 24 hours following operation. Results of the pilot study suggested that TENS
      applied to acupuncture points enhanced pain relief. Patients in the follow-up
      trial had similar pain scores. Those given TENS to non-true acupuncture points
      required more morphine than those given TENS to true points, suggesting that
      endogenous opioids released from acupuncture points were boosting pain relief.

PMID- 29328860
TI  - Quality of Life From Canadian Cancer Trials Group MA.17R: A Randomized Trial of
      Extending Adjuvant Letrozole to 10 Years.
AB  - Purpose MA.17R was a Canadian Cancer Trials Group-led phase III randomized
      controlled trial comparing letrozole to placebo after 5 years of aromatase
      inhibitor as adjuvant therapy for hormone receptor-positive breast cancer.
      Quality of life (QOL) was a secondary outcome measure of the study, and here, we
      report the results of these analyses. Methods QOL was measured using the Short
      Form-36 (SF-36; two summary scores and eight domains) and menopause-specific QOL
      (MENQOL; four symptom domains) at baseline and every 12 months up to 60 months.
      QOL assessment was mandatory for Canadian Cancer Trials Group centers but
      optional for centers in other groups. Mean change scores from baseline were
      calculated. Results One thousand nine hundred eighteen women were randomly
      assigned, and 1,428 women completed the baseline QOL assessment. Compliance with
      QOL measures was > 85%. Baseline summary scores for the SF-36 physical component
      summary (47.5 for letrozole and 47.9 for placebo) and mental component summary
      (55.5 for letrozole and 54.8 for placebo) were close to the population norms of
      50. No differences were seen between groups in mean change scores for the SF-36
      physical and mental component summaries and the other eight QOL domains except
      for the role-physical subscale. No difference was found in any of the four
      domains of the MENQOL Conclusion No clinically significant differences were seen
      in overall QOL measured by the SF-36 summary measures and MENQOL between the
      letrozole and placebo groups. The data indicate that continuation of aromatase
      inhibitor therapy after 5 years of prior treatment in the trial population was
      not associated with a deterioration of overall QOL.

PMID- 29328861
TI  - Radiofrequency Ablation Versus Stereotactic Body Radiotherapy for Localized
      Hepatocellular Carcinoma in Nonsurgically Managed Patients: Analysis of the
      National Cancer Database.
AB  - Purpose Data that guide selection of optimal local ablative therapy for the
      management localized hepatocellular carcinoma (HCC) are lacking. Because there
      are limited prospective comparative data for these treatment modalities, we aimed
      to compare the effectiveness of radiofrequency ablation (RFA) versus stereotactic
      body radiotherapy (SBRT) by using the National Cancer Database. Methods We
      conducted an observational study to compare the effectiveness of RFA versus SBRT
      in nonsurgically managed patients with stage I or II HCC. Overall survival was
      compared by using propensity score-weighted and propensity score-matched analyses
      based on patient-, facility-, and tumor-level characteristics. A sensitivity
      analysis was performed to evaluate the effect of severe fibrosis/cirrhosis. In
      addition, we performed exploratory analyses to determine the effectiveness of RFA
      and SBRT in clinically relevant patient subsets. Results Overall, 3,684 (92.6%)
      and 296 (7.4%) nonsurgically managed patients with stage I or II HCC received RFA
      or SBRT, respectively. After propensity matching, 5-year overall survival was
      29.8% (95% CI, 24.5% to 35.3%) in the RFA group versus 19.3% (95% CI, 13.5% to
      25.9%) in the SBRT group ( P < .001). Inverse probability-weighted analysis
      yielded similar results. The benefit of RFA was consistent across all subgroups
      examined and was robust to the effects of severe fibrosis/cirrhosis. Conclusion
      Our study suggests that treatment with RFA yields superior survival compared with
      SBRT for nonsurgically managed patients with stage I or II HCC. Even though our
      results are limited by the biases related to the retrospective study design, we
      believe that, in the absence of a randomized clinical trial, our findings should
      be considered when recommending local ablative therapy for localized unresectable
      HCC.

PMID- 29328862
TI  - What Happens When Proton Meets Randomization: Is There a Future for Proton
      Therapy?

PMID- 29328863
TI  - Overexpression of mTOR and p(240-244)S6 in IDH1 Wild-Type Human Glioblastomas Is
      Predictive of Low Survival.
AB  - PI3K/Akt/mTOR pathway activation is a hallmark of high-grade gliomas, which
      prompted clinical trials for the use of PI3K and mTOR inhibitors. However, the
      poor results in the original trials suggested that better patient profiling was
      needed for such drugs. Thus, accurate and reproducible monitoring of mTOR
      complexes can lead to improved therapeutic strategies. In this work, we evaluated
      the expression and phosphorylation of mTOR, RAPTOR, and rpS6 in 195 human
      astrocytomas and 30 normal brain tissue samples. The expression of mTOR increased
      in glioblastomas, whereas mTOR phosphorylation, expression of RAPTOR, and
      expression and phosphorylation of rpS6 were similar between grades.
      Interestingly, the overexpression of total and phosphorylated mTOR as well as
      phosphorylated rpS6 (residues 240-244) were associated with wild-type IDH1 only
      glioblastomas. The expression and phosphorylation of mTOR and phosphorylation of
      rpS6 at residues 240-244 were associated with a worse prognosis in glioblastomas.
      Our results suggest that mTOR and rpS6 could be used as markers of overactivation
      of the PI3K-mTOR pathway and are predictive factors for overall survival in
      glioblastomas. Our study thus suggests that patients who harbor IDH1 wild-type
      glioblastomas might have increased benefit from targeted therapy against mTOR.

PMID- 29328864
TI  - Building Evidence for Health: Green Buildings, Current Science, and Future
      Challenges.
AB  - Civilizational challenges have questioned the status quo of energy and material
      consumption by humans. From the built environment perspective, a response to
      these challenges was the creation of green buildings. Although the revolutionary
      capacity of the green building movement has elevated the expectations of new
      commercial construction, its rate of implementation has secluded the majority of
      the population from its benefits. Beyond reductions in energy usage and increases
      in market value, the main strength of green buildings may be the procurement of
      healthier building environments. Further pursuing the right to healthy indoor
      environments could help the green building movement to attain its full potential
      as a transformational public health tool. On the basis of 40 years of research on
      indoor environmental quality, we present a summary of nine environment elements
      that are foundational to human health. We posit the role of green buildings as a
      critical research platform within a novel sustainability framework based on
      social-environmental capital assets.

PMID- 29328865
TI  - The Relationship Between Education and Health: Reducing Disparities Through a
      Contextual Approach.
AB  - Adults with higher educational attainment live healthier and longer lives
      compared with their less educated peers. The disparities are large and widening.
      We posit that understanding the educational and macrolevel contexts in which this
      association occurs is key to reducing health disparities and improving population
      health. In this article, we briefly review and critically assess the current
      state of research on the relationship between education and health in the United
      States. We then outline three directions for further research: We extend the
      conceptualization of education beyond attainment and demonstrate the centrality
      of the schooling process to health; we highlight the dual role of education as a
      driver of opportunity but also as a reproducer of inequality; and we explain the
      central role of specific historical sociopolitical contexts in which the
      education-health association is embedded. Findings from this research agenda can
      inform policies and effective interventions to reduce health disparities and
      improve health for all Americans.

PMID- 29328867
TI  - Glioma Stem Cell Niches in Human Glioblastoma Are Periarteriolar.
AB  - Survival of primary brain tumor (glioblastoma) patients is seriously hampered by
      glioma stem cells (GSCs) that are distinct therapy-resistant self-replicating
      pluripotent cancer cells. GSCs reside in GSC niches, which are specific
      protective microenvironments in glioblastoma tumors. We have recently found that
      GSC niches are hypoxic periarteriolar, whereas in most studies, GSC niches are
      identified as hypoxic perivascular. The aim of this review is to critically
      evaluate the literature on perivascular GSC niches to establish whether these are
      periarteriolar, pericapillary, perivenular, and/or perilymphatic. We found six
      publications showing images of human glioblastoma tissue containing perivascular
      GSC niches without any specification of the vessel type. However, it is
      frequently assumed that these vessels are capillaries which are exchange vessels,
      whereas arterioles and venules are transport vessels. Closer inspection of the
      figures of these publications showed vessels that were not capillaries. Whether
      these vessels were arterioles or venules was difficult to determine in one case,
      but in the other cases, these were clearly arterioles and their perivascular
      niches were similar to the periarteriolar niches we have found. Therefore, we
      conclude that in human glioblastoma tumors, GSC niches are hypoxic periarteriolar
      and are structurally and functionally look-alikes of hematopoietic stem cell
      niches in the bone marrow.

PMID- 29328868
TI  - Oral Sciences PhD Program Enrollment, Graduates, and Placement: 1994 to 2016.
AB  - For decades, dental schools in the United States have endured a significant
      faculty shortage. Studies have determined that the top 2 sources of dental
      faculty are advanced education programs and private practice. Those who have
      completed both DDS and PhD training are considered prime candidates for dental
      faculty positions. However, there is no national database to track those trainees
      and no evidence to indicate that they entered academia upon graduation. The
      objective of this study was to assess outcomes of dental school-affiliated oral
      sciences PhD program enrollment, graduates, and placement between 1994 and 2016.
      Using the American Dental Association annual survey of advanced dental education
      programs not accredited by the Commission on Dental Accreditation and data
      obtained from 22 oral sciences PhD programs, we assessed student demographics,
      enrollment, graduation, and placement. Based on the data provided by program
      directors, the average new enrollment was 33, and graduation was 26 per year. A
      total of 605 graduated; 39 did not complete; and 168 were still in training.
      Among those 605 graduates, 211 were faculty in U.S. academic institutions, and 77
      were faculty in foreign institutions. Given that vacant budgeted full-time
      faculty positions averaged 257 per year during this period, graduates from those
      oral sciences PhD programs who entered academia in the United States would have
      filled 9 (3.6%) vacant faculty positions per year. Therefore, PhD programs have
      consistently generated only a small pipeline of dental school faculty. Better
      mentoring to retain talent in academia is necessary. Stronger support and
      creative funding plans are essential to sustain the PhD program. Furthermore, the
      oral sciences PhD program database should be established and maintained by dental
      professional organizations to allow assessments of training models, trends of
      enrollment, graduation, and placement outcomes.

PMID- 29328866
TI  - Proteoglycans as Immunomodulators of the Innate Immune Response to Lung
      Infection.
AB  - Proteoglycans (PGs) are complex, multifaceted molecules that participate in
      diverse interactions vital for physiological and pathological processes. As
      structural components, they provide a scaffold for cells and structural
      organization that helps define tissue architecture. Through interactions with
      water, PGs enable molecular and cellular movement through tissues. Through
      selective ionic interactions with growth factors, chemokines, cytokines, and
      proteases, PGs facilitate the ability of these soluble ligands to regulate
      intracellular signaling events and to influence the inflammatory response. In
      addition, recent findings now demonstrate that PGs can activate danger-associated
      molecular patterns (DAMPs) and other signaling pathways to influence production
      of many of these soluble ligands, indicating a more direct role for PGs in
      influencing the immune response and tissue inflammation. This review will focus
      on PGs that are selectively expressed during lung inflammation and will examine
      the novel emerging concept of PGs as immunomodulatory regulators of the innate
      immune responses in lungs.

PMID- 29328869
TI  - Inflammatory Bowel Diseases and Fermentable Oligosaccharides, Disaccharides,
      Monosaccharides, and Polyols: An Overview.
AB  - Inflammatory bowel diseases (IBDs) are mainly represented by ulcerative colitis
      and Crohn's disease, and the increase in the incidence tends to follow the rapid
      industrialization and lifestyle of modern societies. FODMAP (fermentable
      oligosaccharides, disaccharides, monosaccharides, and polyols) consist of
      molecules that are poorly absorbed in the small intestine and are fermented by
      bacteria in the colon leading to symptoms such as bloating, flatulence, diarrhea,
      and abdominal pain. Reduction of the ingestion of FODMAP could reduce the
      symptoms and improve the quality of life. This review aimed to summarize some
      important aspects of IBD and evaluate the effects of this diet on this
      inflammatory condition. Studies including the term FODMAP (and similar terms) and
      IBD were selected for this review (MEDLINE database was used PubMed/PMC). A low
      FODMAP diet may be an effective tool to the management of the common abdominal
      symptoms in patients with functional gastrointestinal symptoms once these
      molecules trigger these symptoms. This diet may also reduce the expression of pro
      inflammatory markers such as C-reactive protein and fecal calprotectin and may
      interfere with the microbiome and its metabolites. The use of a low FODMAP diet
      can bring benefits to the IBD patients, but may also modify their nutritional
      status. Thus it should be utilized in appropriated conditions, and dietary
      supplements should be necessary to avoid deficiencies that could be caused by a
      low FODMAP diet over long periods. We suggest that further investigations are
      required to elucidate when and how to apply the FODMAP diet in IBD patients.

PMID- 29328871
TI  - Achieving Mental Health and Substance Use Disorder Treatment Parity: A Quarter
      Century of Policy Making and Research.
AB  - The Mental Health Parity and Addiction Equity Act (MHPAEA) of 2008 changed the
      landscape of mental health and substance use disorder coverage in the United
      States. The MHPAEA's comprehensiveness compared with past parity laws, including
      its extension of parity to plan management strategies, the so-called
      nonquantitative treatment limitations (NQTL), led to significant improvements in
      mental health care coverage. In this article, we review the history of this
      landmark legislation and its recent expansions to new populations, describe past
      research on the effects of this and other mental health/substance use disorder
      parity laws, and describe some directions for future research, including NQTL
      compliance issues, effects of parity on individuals with severe mental illness,
      and measurement of benefits other than mental health care use.

PMID- 29328872
TI  - The Sustainability of Evidence-Based Interventions and Practices in Public Health
      and Health Care.
AB  - There is strong interest in implementation science to address the gap between
      research and practice in public health. Research on the sustainability of
      evidence-based interventions has been growing rapidly. Sustainability has been
      defined as the continued use of program components at sufficient intensity for
      the sustained achievement of desirable program goals and population outcomes.
      This understudied area has been identified as one of the most significant
      translational research problems. Adding to this challenge is uncertainty
      regarding the extent to which intervention adaptation and evolution are necessary
      to address the needs of populations that differ from those in which interventions
      were originally tested or implemented. This review critically examines and
      discusses conceptual and methodological issues in studying sustainability,
      summarizes the multilevel factors that have been found to influence the
      sustainability of interventions in a range of public health and health care
      settings, and highlights key areas for future research.

PMID- 29328870
TI  - Agent-Based Modeling in Public Health: Current Applications and Future
      Directions.
AB  - Agent-based modeling is a computational approach in which agents with a specified
      set of characteristics interact with each other and with their environment
      according to predefined rules. We review key areas in public health where agent
      based modeling has been adopted, including both communicable and noncommunicable
      disease, health behaviors, and social epidemiology. We also describe the main
      strengths and limitations of this approach for questions with public health
      relevance. Finally, we describe both methodologic and substantive future
      directions that we believe will enhance the value of agent-based modeling for
      public health. In particular, advances in model validation, comparisons with
      other causal modeling procedures, and the expansion of the models to consider
      comorbidity and joint influences more systematically will improve the utility of
      this approach to inform public health research, practice, and policy.

PMID- 29328873
TI  - Selecting and Improving Quasi-Experimental Designs in Effectiveness and
      Implementation Research.
AB  - Interventional researchers face many design challenges when assessing
      intervention implementation in real-world settings. Intervention implementation
      requires holding fast on internal validity needs while incorporating external
      validity considerations (such as uptake by diverse subpopulations, acceptability,
      cost, and sustainability). Quasi-experimental designs (QEDs) are increasingly
      employed to achieve a balance between internal and external validity. Although
      these designs are often referred to and summarized in terms of logistical
      benefits, there is still uncertainty about (a) selecting from among various QEDs
      and (b) developing strategies to strengthen the internal and external validity of
      QEDs. We focus here on commonly used QEDs (prepost designs with nonequivalent
      control groups, interrupted time series, and stepped-wedge designs) and discuss
      several variants that maximize internal and external validity at the design,
      execution and implementation, and analysis stages.

PMID- 29328874
TI  - Neighborhood Interventions to Reduce Violence.
AB  - Violence is a widespread problem that affects the physical, mental, and social
      health of individuals and communities. Violence comes with an immense economic
      cost to its victims and society at large. Although violence interventions have
      traditionally targeted individuals, changes to the built environment in places
      where violence occurs show promise as practical, sustainable, and high-impact
      preventive measures. This review examines studies that use quasi-experimental or
      experimental designs to compare violence outcomes for treatment and control
      groups before and after a change is implemented in the built environment. The
      most consistent evidence exists in the realm of housing and blight remediation of
      buildings and land. Some evidence suggests that reducing alcohol availability,
      improving street connectivity, and providing green housing environments can
      reduce violent crimes. Finally, studies suggest that neither transit changes nor
      school openings affect community violence.

PMID- 29328875
TI  - Environmental Determinants of Breast Cancer.
AB  - In the United States, breast cancer is the most common invasive malignancy and
      the second most common cause of death from cancer in women. Reproductive factors,
      estrogen, and progesterone have major causal roles, but concerns about other
      potential causes in the external environment continue to drive research inquiries
      and stimulate calls for action at the policy level. The environment is defined as
      anything that is not genetic and includes social, built, and chemical toxicant
      aspects. This review covers the scope of known and suspected environmental
      factors that have been associated with breast cancer and illustrates how
      epidemiology, toxicology, and mechanistic studies work together to create the
      full picture of environmental effects on this malignancy. Newer approaches to
      risk-related evaluations may allow this field to move forward and more clearly
      delineate actionable environmental causes of this most common of cancers in
      women.

PMID- 29328876
TI  - Meta-Analysis of Complex Interventions.
AB  - Meta-analysis is a prominent method for estimating the effects of public health
      interventions, yet these interventions are often complex in ways that pose
      challenges to using conventional meta-analytic methods. This article discusses
      meta-analytic techniques that can be used in research syntheses on the effects of
      complex public health interventions. We first introduce the use of complexity
      frameworks to conceptualize public health interventions. We then present a menu
      of meta-analytic procedures for addressing various sources of complexity when
      answering questions about the effects of public health interventions in research
      syntheses. We conclude with a review of important practices and key resources for
      conducting meta-analyses on complex interventions, as well as future directions
      for research synthesis more generally. Overall, we argue that it is possible to
      conduct meaningful quantitative syntheses of research on the effects of public
      health interventions, though these meta-analyses may require the use of advanced
      techniques to properly consider and attend to issues of complexity.

PMID- 29328877
TI  - Designing Difference in Difference Studies: Best Practices for Public Health
      Policy Research.
AB  - The difference in difference (DID) design is a quasi-experimental research design
      that researchers often use to study causal relationships in public health
      settings where randomized controlled trials (RCTs) are infeasible or unethical.
      However, causal inference poses many challenges in DID designs. In this article,
      we review key features of DID designs with an emphasis on public health policy
      research. Contemporary researchers should take an active approach to the design
      of DID studies, seeking to construct comparison groups, sensitivity analyses, and
      robustness checks that help validate the method's assumptions. We explain the key
      assumptions of the design and discuss analytic tactics, supplementary analysis,
      and approaches to statistical inference that are often important in applied
      research. The DID design is not a perfect substitute for randomized experiments,
      but it often represents a feasible way to learn about casual relationships. We
      conclude by noting that combining elements from multiple quasi-experimental
      techniques may be important in the next wave of innovations to the DID approach.

PMID- 29328878
TI  - Environmental Influences on the Epigenome: Exposure- Associated DNA Methylation
      in Human Populations.
AB  - DNA methylation is the most well studied of the epigenetic regulators in relation
      to environmental exposures. To date, numerous studies have detailed the manner by
      which DNA methylation is influenced by the environment, resulting in altered
      global and gene-specific DNA methylation. These studies have focused on prenatal,
      early-life, and adult exposure scenarios. The present review summarizes currently
      available literature that demonstrates a relationship between DNA methylation and
      environmental exposures. It includes studies on aflatoxin B1, air pollution,
      arsenic, bisphenol A, cadmium, chromium, lead, mercury, polycyclic aromatic
      hydrocarbons, persistent organic pollutants, tobacco smoke, and nutritional
      factors. It also addresses gaps in the literature and future directions for
      research. These gaps include studies of mixtures, sexual dimorphisms with respect
      to environmentally associated methylation changes, tissue specificity, and
      temporal stability of the methylation marks.

PMID- 29328879
TI  - Modeling Health Care Expenditures and Use.
AB  - Health care expenditures and use are challenging to model because these dependent
      variables typically have distributions that are skewed with a large mass at zero.
      In this article, we describe estimation and interpretation of the effects of a
      natural experiment using two classes of nonlinear statistical models: one for
      health care expenditures and the other for counts of health care use. We extend
      prior analyses to test the effect of the ACA's young adult expansion on three
      different outcomes: total health care expenditures, office-based visits, and
      emergency department visits. Modeling the outcomes with a two-part or hurdle
      model, instead of a single-equation model, reveals that the ACA policy increased
      the number of office-based visits but decreased emergency department visits and
      overall spending.

PMID- 29328880
TI  - Relative Roles of Race Versus Socioeconomic Position in Studies of Health
      Inequalities: A Matter of Interpretation.
AB  - An abundance of research has documented health inequalities by race and
      socioeconomic position (SEP) in the United States. However, conceptual and
      methodological challenges complicate the interpretation of study findings,
      thereby limiting progress in understanding health inequalities and in achieving
      health equity. Fundamental to these challenges is a lack of clarity about what
      race is and the implications of that ambiguity for scientific inquiry.
      Additionally, there is wide variability in how SEP is conceptualized and
      measured, resulting in a lack of comparability across studies and significant
      misclassification of risk. The objectives of this review are to synthesize the
      literature regarding common approaches to examining race and SEP health
      inequalities and to discuss the conceptual and methodological challenges
      associated with how race and SEP have been employed in public health research.
      Addressing health inequalities has become increasingly important as the United
      States trends toward becoming a majority-minority nation. Recommendations for
      future research are presented.

PMID- 29328881
TI  - Factors Affecting the Virological Response Among Chronic Hepatitis C Virus
      Patients in Yemen.
AB  - Hepatitis C virus (HCV) infection is increasingly seen as a major public health
      problem, threat, and concern worldwide. In Yemen about 1.7% of the population is
      infected with chronic hepatitis C. This study aimed to detect the predictors for
      response to pegylated interferon and ribavirin (Peg-IFN/RBV) in chronic HCV
      Yemeni patients. The study was conducted on 100 patients with chronic HCV who
      received Peg-IFN/RBV in the 48th Military Hospital in Sana'a Yemen, from 2011 to
      2013. All patients were subjected to complete history taking, thorough clinical
      examinations, routine laboratory investigation, and abdominal ultrasonography.
      The HCV RNA was assessed at week 72 of treatment to detect whether the patient
      achieved sustained virological response (SVR). The SVR was achieved in 64% of the
      samples. Age above 40, Khat chewing, and obesity were the sociodemographic
      factors that predict good response for Peg-IFN/RBV combined therapy. Platelet
      count, alpha feto-protein (AFP), aspartate transaminase (AST), and alanine
      transaminase (ALT) levels were the basic laboratory investigations that gave
      favorable response. Significant predictors of sustained response included: older
      than 40 years (OR = 0.136, P = 0.042), Khat chewer (OR = 0.016, P = 0.008), body
      mass index (BMI) (OR = 0.055, P = 0.029) and increase in fasting blood glucose
      (OR = 0.925, P = 0.004), alkaline phosphatase (OR = 0.969, P = 0.001), total and
      bilirubin (OR = 0.058, P = 0.017), AST (OR = 1.033, P = 0.002), and albumin (OR =
      6.490, P = 0.021). Studying the independent variables of response, we revealed
      that male gender, BMI, ALT >40, AFP >10, viremia >600, and hemoglobin and thyroid
      stimulating hormone (TSH) levels are variables associated with failure of end of
      treatment response (ETR) and SVR.

PMID- 29328882
TI  - Effects of Salvia miltiorrhiza Polysaccharides on Lipopolysaccharide-Induced
      Inflammatory Factor Release in RAW264.7 Cells.
AB  - This study investigated the anti-inflammatory effects and possible underlying
      mechanisms of Salvia miltiorrhiza polysaccharides (SMP) in lipopolysaccharide
      (LPS)-stimulated RAW264.7 cells. The cytotoxicity of SMP was detected by the MTT
      method. The morphological change of RAW264.7 was observed by Diff-Quik staining.
      Enzyme-linked immunosorbent assay was used to evaluate the production of
      cytokines in LPS-induced RAW264.7 cells. The nitric oxide (NO) kit assay detected
      the NO release from LPS-induced RAW264.7 cells. Real-time polymerase chain
      reaction was used to detect the transcriptions of tumor necrosis factor-alpha
      (TNF-alpha), interleukin-6 (IL-6), inducible NO synthase (iNOS), and
      cyclooxygenase (COX)-2 in LPS-induced RAW264.7 cells. The protein expression of
      nuclear NF-kappaB was measured by Western blot. The results showed that the safe
      medication range of SMP was less than 3 mg/mL. Compared with the LPS model group,
      SMP (2, 1, and 0.5 mg/mL) improved the degree of cell deformation and reduced the
      amount of pseudopodia, and statistically reduced the secretions of cytokines in
      cells induced by LPS (P < 0.01) at different time points. SMP significantly
      inhibited the mRNA transcriptions of TNF-alpha, IL-6, iNOS, and COX-2 and the
      protein expressions of NF-kappaB, p-p65, and p-IkappaBa. In conclusion, this
      study preliminarily proved the protective effect of SMP on LPS-induced RAW264.7
      macrophage. Its mechanism might be related to inhibition of NF-kappaB signal
      pathway and the gene expressions and secretion of cytokines.

PMID- 29328883
TI  - A Systematic Review of Interleukin-1beta in Post-Traumatic Stress Disorder:
      Evidence from Human and Animal Studies.
AB  - Pro-inflammatory cytokines, such as interleukin (IL)-1beta, have been implicated
      as underlying pathophysiological mechanisms and potential biomarkers of post
      traumatic stress disorder (PTSD). This systematic review examines data regarding
      IL-1beta production/concentration in human and animal studies of PTSD. In
      accordance with PRISMA guidelines, relevant articles from PubMed were reviewed
      from inception until July 10, 2017. Nineteen studies were eligible for inclusion.
      Animal studies demonstrated increased hippocampal IL-1beta in rodent models of
      PTSD. Several immunomodulatory drugs were shown to reduce elevated IL-1beta
      levels and anxiety-like behaviors in animals. Human cross-sectional studies
      showed contradictory results; serum and plasma IL-1beta concentrations in PTSD
      patients were either elevated or did not differ from control groups. In vitro IL
      1beta production by stimulated cells demonstrated no difference between PTSD and
      control participants, although spontaneous in vitro production of IL-1beta was
      increased in the PTSD group. The findings from 2 longitudinal studies were
      inconsistent. Given the conflicting findings, it is premature to consider IL
      1beta as a biomarker of PTSD. Anti-inflammatory agents may reduce IL-1beta, and
      be a potential basis for future therapeutic agents in PTSD treatment. More
      longitudinal research is needed to better understand the role of IL-1beta in the
      development and/or maintenance of PTSD.

PMID- 29328885
TI  - Radiographic Emphysema, Circulating Bone Biomarkers, and Progressive Bone Mineral
      Density Loss in Smokers.
AB  - RATIONALE: Osteoporosis is common in individuals with chronic obstructive
      pulmonary disease. Lung-specific factors, including radiographic emphysema,
      independently associate with low bone mineral density in cross-sectional smoking
      cohorts. However, factors associated with progressive bone loss in smokers are
      understudied and largely unknown. OBJECTIVES: To determine the relationship
      between radiographic emphysema, circulating bone metabolism markers, and
      pulmonary function and accelerated bone mineral density loss in smokers. METHODS:
      Two hundred and forty male and female current and former smokers, 40 years of age
      or older, underwent baseline and 2-year assessments of pulmonary function,
      computed tomography-assessed emphysema, dual X-ray absorptiometry-measured bone
      mineral density, and circulating bone metabolism biomarker levels (type I
      collagen C-telopeptide [CTX], amino-terminal propeptide of type I procollagen
      [P1NP]). The association of radiographic emphysema, bone metabolism biomarker
      levels, and pulmonary function with accelerated hip bone mineral density loss,
      defined by the 75th percentile of annual hip bone mineral density decline, was
      determined by logistic regression modeling with adjustment for age, sex, inhaled
      and intermittent steroid use, active smoking, body mass index, and the presence
      of baseline low hip bone mineral density. RESULTS: Of those participants with
      accelerated hip bone mineral density loss, 22% had moderate or severe visually
      assessed emphysema compared with 7.2% of smokers without accelerated bone mineral
      density decline. Moderate to severe visually assessed emphysema (odds ratio,
      2.84; 95% confidence interval, 1.01-7.98 compared with trace/mild or no visually
      assessed emphysema) and the 75th percentile of CTX levels (odds ratio, 2.38; 95%
      confidence interval, 1.20-4.72 compared with CTX levels below the 75th
      percentile), a marker of bone resorption, were associated with accelerated hip
      bone mineral density decline after adjustment for covariates and the presence of
      baseline low hip bone mineral density. FEV1% predicted was not associated with
      accelerated bone mineral density decline after adjustment for covariates.
      Multivariate modeling showed moderate to severe visually assessed emphysema, and
      the 75th percentiles of CTX were independently associated with accelerated hip
      bone mineral density decline after adjustment for covariates. CONCLUSIONS:
      Emphysema and elevated markers of bone resorption are independently associated
      with progressive bone mineral density loss in smokers. These clinical markers may
      guide targeted bone mineral density screening and monitoring in smokers at
      highest risk.

PMID- 29328884
TI  - Evaluation of G2 Citric Acid-Based Dendrimer as an Adjuvant in Veterinary Rabies
      Vaccine.
AB  - For induction of an appropriate immune response, especially in the case of an
      inactivated vaccine, the use of an adjuvant is crucial. In this study,
      adjuvanticity effect of G2 dendrimer in veterinary rabies vaccine has been
      investigated. A nonlinear globular G2 dendrimer comprising citric acid and
      polyethylene glycol 600 (PEG-600) was synthesized and the toxicity was studied in
      vitro on the J774A.1 cell line. The adjuvanticity effect of the dendrimer was
      then investigated on rabies virus in NMRI mice as a model. Different
      concentrations of dendrimer were used to determine the best formulation for the
      survival of the mice after virus challenge. The rise of neutralizing antibody was
      also checked by rapid fluorescent focus inhibition test (RFFIT). The relative
      potency of the prepared formulation was finally calculated using standard NIH
      test and the results were compared (and discussed) with the commercially
      available rabies vaccine. The accuracy of dendrimer synthesis was confirmed using
      Fourier transform infrared (FT-IR), size, and zeta potential analysis. The in
      vitro toxicity assay revealed that no significant toxic effect is observed in
      cells when data are compared with the control group. The in vivo assay showed
      that a higher survival rate in the mice received a special formulation due to
      adjuvanticity effect of dendrimer, which is also confirmed by RFFIT. However, the
      relative potency of that formulation does not give expected results when compared
      with the alum-containing rabies vaccine. In the current investigation, the
      adjuvanticity effect of G2 dendrimer was demonstrated for the first time in
      rising of neutralizing antibodies against rabies virus. Our data confirm that
      nanoparticles can enhance immune responses in an appropriate manner. Moreover,
      engineered nanoparticles will enable us to develop novel potent multivalent
      adjuvants in vaccine technology.

PMID- 29328886
TI  - Osteochondral Graft Size Is Significantly Associated With Increased Force and
      Decreased Chondrocyte Viability.
AB  - BACKGROUND: Insertion force has been shown to significantly reduce chondrocyte
      viability during osteochondral allograft transplantation. How graft size
      influences the required insertion force and chondrocyte viability has yet to be
      determined. Hypothesis/Purpose: The purpose was to characterize how graft size
      influences insertion force requirements and chondrocyte viability during
      osteochondral transplantation. The hypothesis was that larger grafts would
      require greater force and reduce chondrocyte viability. STUDY DESIGN: Controlled
      laboratory study. METHODS: Four graft sizes-15 * 5 mm, 15 * 10 mm, 25 * 5 mm, and
      25 * 10 mm (diameter * depth)-were harvested from 13 thawed fresh-frozen human
      cadaveric distal femurs. Average, maximum, and cumulative force and number of
      impacts were recorded for 44 grafts by a surgical mallet embedded with a
      calibrated force sensor. In a separate experiment, fresh osteochondral tissues
      were subjected to mechanical loading. To capture a range of clinically important
      forces, categories were selected to correspond to impaction force data.
      Chondrocyte viability was assessed with confocal laser microscopy and live/dead
      staining. RESULTS: Total force for all grafts averaged 4576 N. Median number of
      impacts for all grafts was 20 (range, 7-116). The mean number of impacts for 5-mm
      deep grafts was 14.2 (95% CI, 10.8-18.6), as compared with 26.3 (95% CI, 19.9
      34.4) for 10-mm-deep grafts ( P < .001). The mean cumulative force for 5-mm-deep
      grafts was 2128 N (95% CI, 1467-3087), as opposed to 4689 N (95% CI, 3232-6803)
      for 10-mm-deep grafts ( P = .001). For every 1 mm in graft depth, an average of
      13.1% (95% CI, 6.2%-20.3%) more impacts are required when controlling for
      diameter and density ( P < .001). For every 1 mm in graft depth, the force
      required increases on average by 17.1% (95% CI, 7.7%-27.4%) when controlling for
      diameter and density ( P = .001). There was a significant reduction in
      chondrocyte viability for the forces required for graft thickness values >10 mm.
      Only forces associated with graft thickness <10 mm had chondrocyte viabilities
      consistently >70%. CONCLUSION: Insertion force increases significantly with
      increasing graft depth. Controlling for diameter and bone density, a 1-mm
      increase in graft depth is associated with 13.1% more impacts and 17.1% more
      force. Chondrocyte viability was significantly reduced to <70% at average forces
      associated with grafts thicker than 10 mm. CLINICAL RELEVANCE: Based on the
      current data, graft depth is an important consideration for surgeons when sizing
      osteochondral allograft transplant for chondral lesions of the knee.

PMID- 29328888
TI  - Posterior Cruciate Ligament Reconstruction With Transtibial or Tibial Inlay
      Techniques: A Meta-analysis of Biomechanical and Clinical Outcomes.
AB  - BACKGROUND: Transtibial (TT) or tibial inlay (TI) techniques are commonly used
      for posterior cruciate ligament reconstruction (PCLR). However, the optimum
      method for PCLR after PCL injury remains debatable. Hypothesis/Purpose: The
      hypothesis was that TT and TI techniques would not show significant differences
      for all outcome measures. The purpose was to determine the biomechanical and
      clinical outcomes of TT and TI surgical techniques for PCLR. STUDY DESIGN: Meta
      analysis; Level of evidence, 3. METHODS: MEDLINE, EMBASE, the Cochrane Central
      Register of Controlled Trials (CENTRAL), Web of Science, and SCOPUS electronic
      databases for articles published up until August 2016 were searched to find
      relevant articles comparing outcomes of TT versus TI techniques for PCLR. Data
      searching, extraction, analysis, and quality assessment were performed according
      to Cochrane Collaboration guidelines. Biomechanical outcomes and clinical
      outcomes of both techniques were compared. Results are presented as risk ratio
      (RR) for binary outcomes and weighted mean difference (WMD) for continuous
      outcomes with 95% confidence intervals (CI). RESULTS: Five biomechanical and 5
      clinical studies were included. No significant biomechanical differences were
      found regarding posterior tibial translation (PTT) at a knee flexion angle of 90
      degrees  or PTT after cyclic loading between the 2 groups. However, a stronger in
      situ force in the graft was detected in the TT group (WMD = 15.58; 95% CI, 0.22
      30.95; I2 = 10%). Although no significant differences were found in clinical
      outcomes such as Lysholm knee function score, Tegner activity score, side-to-side
      difference, or posterior drawer test at final follow-up between the 2 groups, the
      TT technique tended to entail fewer perioperative complications than the TI
      technique (RR = 0.60; 95% CI, 0.35-1.00; I2 = 0%). CONCLUSION: TT and TI
      techniques for PCLR can both restore normal knee kinematics and improve knee
      function. However, the issue of which yields better improvement in stability and
      functional recovery of the knee remains unclear. More high-quality trials and
      randomized controlled trials are needed. Although PCLR via the TT technique
      resulted in higher graft forces, determining whether this is clinically
      significant will require further studies. When performing the TI technique,
      surgeons should inform patients of the risk of complications.

PMID- 29328887
TI  - Macroscopic Rotator Cuff Tendinopathy and Histopathology Do Not Predict Repair
      Outcomes of Rotator Cuff Tears.
AB  - BACKGROUND: Numerous studies have identified factors that may affect the chances
      of rotator cuff healing after surgery. Intraoperative tendon quality may be used
      to predict healing and to determine type of repair and/or consideration of
      augmentation. There are no data that correlate how gross tendon morphology and
      degree of tendinopathy affect patient outcome or postoperative tendon healing.
      Purpose/Hypothesis: The purposes of this study were to (1) compare the gross
      appearance of the tendon edge during arthroscopic rotator cuff repair with its
      histological degree of tendinopathy and (2) determine if gross appearance
      correlated with postoperative repair integrity. The hypothesis was that gross
      (macroscopic) tendon with normal thickness, no delamination, and elastic tissue
      before repair would have a correlation with low Bonar scores, higher
      postoperative American Shoulder and Elbow Surgeons (ASES) scores, and increased
      rates of postoperative tendon healing on ultrasound. STUDY DESIGN: Cross
      sectional study; Level of evidence, 3. METHODS: A total of 105 patients
      undergoing repair of medium-size (1-3 cm) full-thickness rotator cuff tears were
      enrolled in the study. Intraoperatively, the supraspinatus tendon was rated on
      thickness, fraying, and stiffness. Tendon tissue was recovered for histological
      analysis based on the Bonar scoring system. Postoperative ASES and ultrasound
      assessment of healing were obtained 1 year after repair. Correlation between
      gross appearance of the tendon and rotator cuff histology was determined.
      RESULTS: Of the 105 patients, 85 were followed the study to completion. The mean
      age of the patients was 61.6 years; Bonar score, 7.5; preoperative ASES score,
      49; and postoperative ASES score, 86. Ninety-one percent of repairs were intact
      on ultrasound. Gross appearance of torn rotator cuff tendon tissue did not
      correlate with histological appearance. Neither histological (Bonar) score nor
      gross appearance correlated with multivariate analysis of ASES score,
      postoperative repair status, or demographic data. CONCLUSION: The degree of
      tendinopathy did not correlate with morphological appearance of the tendon.
      Neither of these parameters correlated with healing or patient outcome. This
      study suggests that the degree of tendinopathy, unlike muscle atrophy, may not be
      predictive of outcomes and that, on appearance, poor quality tendon has adequate
      healing capacity. Therefore, abnormal gross tendon appearance should not affect
      the repair effort or technique.

PMID- 29328889
TI  - Respiratory Phenotypes for Preterm Infants, Children, and Adults:
      Bronchopulmonary Dysplasia and More.
AB  - Ongoing advancements in neonatal care since the late 1980s have led to increased
      numbers of premature infants surviving well beyond the neonatal period. As a
      result of increased survival, many individuals born preterm manifest chronic
      respiratory symptoms throughout infancy, childhood, and adult life. The
      archetypical respiratory disease of prematurity, bronchopulmonary dysplasia, is
      the second most common chronic pediatric respiratory disease after asthma.
      However, there are several commonly held misconceptions. These misconceptions
      include that bronchopulmonary dysplasia is rare, that bronchopulmonary dysplasia
      resolves within the first few years of life, and that bronchopulmonary dysplasia
      does not impact respiratory health in adult life. This focused review describes a
      spectrum of respiratory conditions that individuals born prematurely may
      experience throughout their lifespan. Specifically, this review provides
      quantitative estimates of the number of individuals with alveolar, airway, and
      vascular phenotypes associated with bronchopulmonary dysplasia, as well as non
      bronchopulmonary dysplasia respiratory phenotypes such as airway malacia,
      obstructive sleep apnea, and control of breathing issues. Furthermore, this
      review illustrates what is known about the potential for progression and/or lack
      of resolution of these respiratory phenotypes in childhood and adult life.
      Recognizing the spectrum of respiratory phenotypes associated with individuals
      born preterm and providing comprehensive and personalized care to these
      individuals may help to modulate adverse respiratory outcomes in later life.

PMID- 29328891
TI  - Dysplasia Should Not Be Ignored in Lichenoid Mucositis.
AB  - Oral lichen planus is categorized as a potentially malignant condition by the
      World Health Organization; however, some argue that only lichen planus with
      dysplasia have malignant potential. Many pathologists call lichen planus with
      dysplasia "dysplasia with lichenoid mucositis (LM)" or "LM with dysplasia."
      Previous research has shown that certain high-risk patterns of loss of
      heterozygosity (LOH) in dysplastic lesions are associated with significantly
      increased cancer risk. However, LM without dysplasia lacks such molecular
      patterns, supporting the hypothesis that LM, by itself, is not potentially
      malignant and that only those with dysplasia have malignant potential. To further
      investigate the premalignant nature of LM with dysplasia, this study compared the
      rate of malignant progression of dysplasia with LM with that of dysplasia without
      LM. Patients from a population-based prospective cohort study with >10 y of
      follow-up were analyzed. Study eligibility included a histological diagnosis of a
      primary low-grade dysplasia with or without LM. A total of 446 lesions in 446
      patients met the selection criteria; 373 (84%) were classified as dysplasia
      without LM, while 73 (16%) were classified as dysplasia with LM. Demographic and
      habit information, clinical information, and outcome (progression) were compared
      between the 2 groups. Forty-nine of 373 cases of dysplasia (13%) progressed
      compared to 8% (6/73) of dysplasia with LM. However, the difference was not
      statistically different ( P = 0.24). The 3- and 5-y rate of progression did not
      differ between the groups (6.7% and 12.5% for dysplasia without LM and 2.9% and
      6.6% for those with LM; P = 0.36). Progression was associated with nonsmoking,
      location at a high-risk site, and diagnosis of moderate dysplasia regardless of
      whether LM was present or not. Dysplasia with or without LM had similar cancer
      risk, and dysplasia should not be discounted in the presence of LM.

PMID- 29328892
TI  - A New Year's transition and looking forward.

PMID- 29328893
TI  - Quality in urine microscopy: The eyes of the beholder.

PMID- 29328894
TI  - Frailty and cardiovascular disease: A two-way street?

PMID- 29328895
TI  - What is the hepatitis B vaccination regimen in chronic kidney disease?

PMID- 29328896
TI  - Do cardiac risk stratification indexes accurately estimate perioperative risk in
      noncardiac surgery patients?

PMID- 29328897
TI  - High users of healthcare: Strategies to improve care, reduce costs.
AB  - A minority of patients consume a disproportionate amount of healthcare,
      especially in the emergency department. These "high users" are a small but
      complex group whose expenses are driven largely by low socioeconomic status,
      mental illness, and drug abuse; lack of social services also contributes. Several
      promising efforts aimed at improving quality and reducing healthcare costs for
      high users include care management organizations, patient care plans, and better
      discharge summaries.

PMID- 29328898
TI  - Idiopathic hypercalciuria: Can we prevent stones and protect bones?
AB  - Idiopathic hypercalciuria increases the risk of urinary stones and osteoporosis.
      The aim of this review is to delineate our current understanding of idiopathic
      hypercalciuria in the context of bone health, specifically its definition,
      causes, epidemiology, laboratory evaluation, and potential treatments.

PMID- 29328899
TI  - Preventing cardiovascular disease in older adults: One size does not fit all.
AB  - Frailty and cardiovascular disease are highly interconnected and increase in
      prevalence with age. Identifying frailty allows for a personalized cardiovascular
      risk prescription and individualized management of hypertension, hyperlipidemia,
      diabetes, and lifestyle in the aging population.

PMID- 29328900
TI  - Detecting and managing device leads inadvertently placed in the left ventricle.
AB  - Inadvertent malpositioning of a cardiac implantable electronic device lead into
      the left ventricle is a rare complication of transvenous pacing and
      defibrillation. Rapid identification of lead position is critical during
      implantation and just after the procedure, with immediate correction required if
      malpositioning is detected. If lead misplacement is discovered late after
      implantation, the lead should be surgically removed or chronic anticoagulation
      with warfarin should be instituted.

PMID- 29328901
TI  - A 50-year-old woman with new-onset seizure.

PMID- 29328902
TI  - Hypothermia and severe first-degree heart block.

PMID- 29328903
TI  - Dysmorphic red blood cell formation.

PMID- 29328904
TI  - Further comments on "High-titre inhibitors in previously untreated patients with
      severe haemophilia A receiving recombinant or plasma-derived factor VIII: a
      budget-impact analysis".

PMID- 29328906
TI  - Importance of information provision in the acceptance of blood donation criteria
      by the general public in Belgium.
AB  - BACKGROUND: Blood transfusions save lives, but carry the risk of causing
      transfusion-transmitted diseases. This risk is limited by strict donor selection
      criteria, the most controversial being the exclusion of men who had sex with men
      (MSM). This cross-sectional study investigated knowledge and beliefs of the
      general public concerning donor exclusion criteria, with emphasis on MSM.
      MATERIALS AND METHODS: A representative sample of the population of Flanders,
      Belgium was questioned using a web-based questionnaire. The effect of additional
      information on people's opinions was tested. RESULTS: People were less aware of
      the exclusion of MSM than of other risk populations, e.g. prostitutes.
      Correspondingly, they were more willing to accept blood from MSM than from other
      risk populations. MSM were also considered appropriate donors. Interestingly,
      prior knowledge about the exclusion of MSM appeared to be the strongest predictor
      for not accepting blood from MSM or a more stringent attitude on MSM exclusion.
      Receiving information on reasons for exclusion shifted opinions towards more
      stringency. Nevertheless, most people think that exceptions for MSM should be
      made under certain circumstances. This study identified several demographic
      factors associated with opinions concerning the exclusion of MSM for blood
      donation and the potential to change opinions after receiving information, e.g.
      age or socio-economic status. DISCUSSION: Blood collecting services can gain
      understanding from the general public about their exclusion policies by providing
      clear information. Communication efforts targeting specific audiences in function
      of their knowledge and likeliness to change their opinion, might improve the
      effectiveness of information campaigns.

PMID- 29328905
TI  - Diagnosis and care of patients with mild haemophilia: practical recommendations
      for clinical management.
AB  - Mild haemophilia is defined by factor levels between 0.05 and 0.40 IU/mL and is
      characterised by traumatic bleeds. Major issues associated with mild haemophilia
      are that it may not present for many years after birth, and that awareness, even
      within families, may be low. Methodological problems exist in diagnosis, such as
      inconsistencies in results obtained from different assays used to measure factor
      levels in mild haemophilia. Advances in genetic testing provide insight into
      diagnosis as well as the likelihood of inhibitor development, which is not
      uncommon in patients with mild or moderate haemophilia and can increase
      morbidity. The management of patients with mild haemophilia is a challenge. This
      review includes suggestions around formulating treatment plans for these
      patients, encompassing the full spectrum from clinical care of the newly
      diagnosed neonate to that of the ageing patient with multiple comorbidities.
      Management strategies consider not only the vast differences in these patients'
      needs, but also risks of inhibitor development and approaches to optimally engage
      patients.

PMID- 29328907
TI  - Weaving New Insights for the Genetic Regulation of Human Cognitive Phenotypes.
AB  - Psychiatric genetic studies have drawn associations between human cognitive
      traits and noncoding genomic variants. However, the mechanistic effects of these
      variants are unclear. By weaving in strands of genomic data from developing human
      brains, de la Torre-Ubieta et al. tie disease-associated loci to functional
      enhancers, target genes, and putatively affected cell types.

PMID- 29328908
TI  - Metabolic Induction of Trained Immunity through the Mevalonate Pathway.
AB  - Innate immune cells can develop long-term memory after stimulation by microbial
      products during infections or vaccinations. Here, we report that metabolic
      signals can induce trained immunity. Pharmacological and genetic experiments
      reveal that activation of the cholesterol synthesis pathway, but not the
      synthesis of cholesterol itself, is essential for training of myeloid cells.
      Rather, the metabolite mevalonate is the mediator of training via activation of
      IGF1-R and mTOR and subsequent histone modifications in inflammatory pathways.
      Statins, which block mevalonate generation, prevent trained immunity induction.
      Furthermore, monocytes of patients with hyper immunoglobulin D syndrome (HIDS),
      who are mevalonate kinase deficient and accumulate mevalonate, have a
      constitutive trained immunity phenotype at both immunological and epigenetic
      levels, which could explain the attacks of sterile inflammation that these
      patients experience. Unraveling the role of mevalonate in trained immunity
      contributes to our understanding of the pathophysiology of HIDS and identifies
      novel therapeutic targets for clinical conditions with excessive activation of
      trained immunity.

PMID- 29328909
TI  - Single-Cell Genomics: A Stepping Stone for Future Immunology Discoveries.
AB  - The immunology field has invested great efforts and ingenuity to characterize the
      various immune cell types and elucidate their functions. However, accumulating
      evidence indicates that current technologies and classification schemes are
      limited in their ability to account for the functional heterogeneity of immune
      processes. Single-cell genomics hold the potential to revolutionize the way we
      characterize complex immune cell assemblies and study their spatial organization,
      dynamics, clonal distribution, pathways, function, and crosstalks. In this
      Perspective, we consider recent and forthcoming technological and analytical
      advances in single-cell genomics and the potential impact of those advances on
      the future of immunology research and immunotherapy.

PMID- 29328911
TI  - Western Diet Triggers NLRP3-Dependent Innate Immune Reprogramming.
AB  - Long-term epigenetic reprogramming of innate immune cells in response to
      microbes, also termed "trained immunity," causes prolonged altered cellular
      functionality to protect from secondary infections. Here, we investigated whether
      sterile triggers of inflammation induce trained immunity and thereby influence
      innate immune responses. Western diet (WD) feeding of Ldlr-/- mice induced
      systemic inflammation, which was undetectable in serum soon after mice were
      shifted back to a chow diet (CD). In contrast, myeloid cell responses toward
      innate stimuli remained broadly augmented. WD-induced transcriptomic and
      epigenomic reprogramming of myeloid progenitor cells led to increased
      proliferation and enhanced innate immune responses. Quantitative trait locus
      (QTL) analysis in human monocytes trained with oxidized low-density lipoprotein
      (oxLDL) and stimulated with lipopolysaccharide (LPS) suggested inflammasome
      mediated trained immunity. Consistently, Nlrp3-/-/Ldlr-/- mice lacked WD-induced
      systemic inflammation, myeloid progenitor proliferation, and reprogramming.
      Hence, NLRP3 mediates trained immunity following WD and could thereby mediate the
      potentially deleterious effects of trained immunity in inflammatory diseases.

PMID- 29328910
TI  - Modulation of Myelopoiesis Progenitors Is an Integral Component of Trained
      Immunity.
AB  - Trained innate immunity fosters a sustained favorable response of myeloid cells
      to a secondary challenge, despite their short lifespan in circulation. We thus
      hypothesized that trained immunity acts via modulation of hematopoietic stem and
      progenitor cells (HSPCs). Administration of beta-glucan (prototypical trained
      immunity-inducing agonist) to mice induced expansion of progenitors of the
      myeloid lineage, which was associated with elevated signaling by innate immune
      mediators, such as IL-1beta and granulocyte-macrophage colony-stimulating factor
      (GM-CSF), and with adaptations in glucose metabolism and cholesterol
      biosynthesis. The trained-immunity-related increase in myelopoiesis resulted in a
      beneficial response to secondary LPS challenge and protection from chemotherapy
      induced myelosuppression in mice. Therefore, modulation of myeloid progenitors in
      the bone marrow is an integral component of trained immunity, which to date, was
      considered to involve functional changes of mature myeloid cells in the
      periphery.

PMID- 29328913
TI  - An Integrated View of Immunometabolism.
AB  - The worldwide obesity epidemic has emerged as a major cause of insulin resistance
      and Type 2 diabetes. Chronic tissue inflammation is a well-recognized feature of
      obesity, and the field of immunometabolism has witnessed many advances in recent
      years. Here, we review the major features of our current understanding with
      respect to chronic obesity-related inflammation in metabolic tissues and focus on
      how these inflammatory changes affect insulin sensitivity, insulin secretion,
      food intake, and glucose homeostasis. There is a growing appreciation of the
      varied and sometimes integrated crosstalk between cells within a tissue
      (intraorgan) and tissues within an organism (interorgan) that supports
      inflammation in the context of metabolic dysregulation. Understanding these
      pathways and modes of communication has implications for translational studies.
      We also briefly summarize the state of this field with respect to potential
      current and developing therapeutics.

PMID- 29328912
TI  - BCG Educates Hematopoietic Stem Cells to Generate Protective Innate Immunity
      against Tuberculosis.
AB  - The dogma that adaptive immunity is the only arm of the immune response with
      memory capacity has been recently challenged by several studies demonstrating
      evidence for memory-like innate immune training. However, the underlying
      mechanisms and location for generating such innate memory responses in vivo
      remain unknown. Here, we show that access of Bacillus Calmette-Guerin (BCG) to
      the bone marrow (BM) changes the transcriptional landscape of hematopoietic stem
      cells (HSCs) and multipotent progenitors (MPPs), leading to local cell expansion
      and enhanced myelopoiesis at the expense of lymphopoiesis. Importantly, BCG
      educated HSCs generate epigenetically modified macrophages that provide
      significantly better protection against virulent M. tuberculosis infection than
      naive macrophages. By using parabiotic and chimeric mice, as well as adoptive
      transfer approaches, we demonstrate that training of the monocyte/macrophage
      lineage via BCG-induced HSC reprogramming is sustainable in vivo. Our results
      indicate that targeting the HSC compartment provides a novel approach for vaccine
      development.

PMID- 29328914
TI  - Rewiring of the Fruit Metabolome in Tomato Breeding.
AB  - Humans heavily rely on dozens of domesticated plant species that have been
      further improved through intensive breeding. To evaluate how breeding changed the
      tomato fruit metabolome, we have generated and analyzed a dataset encompassing
      genomes, transcriptomes, and metabolomes from hundreds of tomato genotypes. The
      combined results illustrate how breeding globally altered fruit metabolite
      content. Selection for alleles of genes associated with larger fruits altered
      metabolite profiles as a consequence of linkage with nearby genes. Selection of
      five major loci reduced the accumulation of anti-nutritional steroidal
      glycoalkaloids in ripened fruits, rendering the fruit more edible. Breeding for
      pink tomatoes modified the content of over 100 metabolites. The introgression of
      resistance genes from wild relatives in cultivars also resulted in major and
      unexpected metabolic changes. The study reveals a multi-omics view of the
      metabolic breeding history of tomato, as well as provides insights into
      metabolome-assisted breeding and plant biology.

PMID- 29328915
TI  - Retrovirus-like Gag Protein Arc1 Binds RNA and Traffics across Synaptic Boutons.
AB  - Arc/Arg3.1 is required for synaptic plasticity and cognition, and mutations in
      this gene are linked to autism and schizophrenia. Arc bears a domain resembling
      retroviral/retrotransposon Gag-like proteins, which multimerize into a capsid
      that packages viral RNA. The significance of such a domain in a plasticity
      molecule is uncertain. Here, we report that the Drosophila Arc1 protein forms
      capsid-like structures that bind darc1 mRNA in neurons and is loaded into
      extracellular vesicles that are transferred from motorneurons to muscles. This
      loading and transfer depends on the darc1-mRNA 3' untranslated region, which
      contains retrotransposon-like sequences. Disrupting transfer blocks synaptic
      plasticity, suggesting that transfer of dArc1 complexed with its mRNA is required
      for this function. Notably, cultured cells also release extracellular vesicles
      containing the Gag region of the Copia retrotransposon complexed with its own
      mRNA. Taken together, our results point to a trans-synaptic mRNA transport
      mechanism involving retrovirus-like capsids and extracellular vesicles.

PMID- 29328917
TI  - Immune Training Unlocks Innate Potential.
AB  - Trained immunity is a form of innate immune memory with distinct features from
      classical adaptive immune memory. In the current issues of Cell and Cell Host &
      Microbe, five studies from the International Trained Immunity Consortium shed
      light on mechanisms and functional consequences of this phenomenon on cellular
      and whole-organism levels.

PMID- 29328916
TI  - The Neuronal Gene Arc Encodes a Repurposed Retrotransposon Gag Protein that
      Mediates Intercellular RNA Transfer.
AB  - The neuronal gene Arc is essential for long-lasting information storage in the
      mammalian brain, mediates various forms of synaptic plasticity, and has been
      implicated in neurodevelopmental disorders. However, little is known about Arc's
      molecular function and evolutionary origins. Here, we show that Arc self
      assembles into virus-like capsids that encapsulate RNA. Endogenous Arc protein is
      released from neurons in extracellular vesicles that mediate the transfer of Arc
      mRNA into new target cells, where it can undergo activity-dependent translation.
      Purified Arc capsids are endocytosed and are able to transfer Arc mRNA into the
      cytoplasm of neurons. These results show that Arc exhibits similar molecular
      properties to retroviral Gag proteins. Evolutionary analysis indicates that Arc
      is derived from a vertebrate lineage of Ty3/gypsy retrotransposons, which are
      also ancestors to retroviruses. These findings suggest that Gag retroelements
      have been repurposed during evolution to mediate intercellular communication in
      the nervous system.

PMID- 29328918
TI  - Transmembrane Pickets Connect Cyto- and Pericellular Skeletons Forming Barriers
      to Receptor Engagement.
AB  - Phagocytic receptors must diffuse laterally to become activated upon clustering
      by multivalent targets. Receptor diffusion, however, can be obstructed by
      transmembrane proteins ("pickets") that are immobilized by interacting with the
      cortical cytoskeleton. The molecular identity of these pickets and their role in
      phagocytosis have not been defined. We used single-molecule tracking to study the
      interaction between Fcgamma receptors and CD44, an abundant transmembrane protein
      capable of indirect association with F-actin, hence likely to serve as a picket.
      CD44 tethers reversibly to formin-induced actin filaments, curtailing receptor
      diffusion. Such linear filaments predominate in the trailing end of polarized
      macrophages, where receptor mobility was minimal. Conversely, receptors were most
      mobile at the leading edge, where Arp2/3-driven actin branching predominates.
      CD44 binds hyaluronan, anchoring a pericellular coat that also limits receptor
      displacement and obstructs access to phagocytic targets. Force must be applied to
      traverse the pericellular barrier, enabling receptors to engage their targets.

PMID- 29328920
TI  - SnapShot: Mitochondrial Nucleoid.
AB  - Mitochondrial DNA is compacted into nucleoprotein complexes denoted mitochondrial
      nucleoids, the focus of this SnapShot.

PMID- 29328919
TI  - Color Processing in the Early Visual System of Drosophila.
AB  - Color vision extracts spectral information by comparing signals from
      photoreceptors with different visual pigments. Such comparisons are encoded by
      color-opponent neurons that are excited at one wavelength and inhibited at
      another. Here, we examine the circuit implementation of color-opponent processing
      in the Drosophila visual system by combining two-photon calcium imaging with
      genetic dissection of visual circuits. We report that color-opponent processing
      of UVshort/blue and UVlong/green is already implemented in R7/R8 inner
      photoreceptor terminals of "pale" and "yellow" ommatidia, respectively. R7 and R8
      photoreceptors of the same type of ommatidia mutually inhibit each other directly
      via HisCl1 histamine receptors and receive additional feedback inhibition that
      requires the second histamine receptor Ort. Color-opponent processing at the
      first visual synapse represents an unexpected commonality between Drosophila and
      vertebrates; however, the differences in the molecular and cellular
      implementation suggest that the same principles evolved independently.

PMID- 29328922
TI  - A Viral (Arc)hive for Metazoan Memory.
AB  - Arc, a master regulator of synaptic plasticity, contains sequence elements that
      are evolutionarily related to retrotransposon Gag genes. Two related papers in
      this issue of Cell show that Arc retains retroviral-like capsid-forming ability
      and can transmit mRNA between cells in the nervous system, a process that may be
      important for synaptic function.

PMID- 29328921
TI  - Tomato Multiomics Reveals Consequences of Crop Domestication and Improvement.
AB  - Genome-scale analyses of variation, gene expression, and metabolite accumulation
      in ancestral, early domesticates, and modern tomatoes by Zhu et al. identify
      genes underlying fruit chemistry and demonstrate that alleles affecting metabolic
      quality have been bred into modern varieties as a result of linkage drag. Similar
      metabolic hitchhikers are likely ubiquitous in other domesticated species.

PMID- 29328924
TI  - Reply by Authors.

PMID- 29328923
TI  - Editorial Comment.

PMID- 29328927
TI  - Alzheimer's disease biomarker-guided diagnostic workflow using the added value of
      six combined cerebrospinal fluid candidates: Abeta1-42, total-tau, phosphorylated
      tau, NFL, neurogranin, and YKL-40.
AB  - INTRODUCTION: The diagnostic and classificatory performances of all combinations
      of three core (amyloid beta peptide [i.e., Abeta1-42], total tau [t-tau], and
      phosphorylated tau) and three novel (neurofilament light chain protein,
      neurogranin, and YKL-40) cerebrospinal fluid biomarkers of neurodegeneration were
      compared among individuals with mild cognitive impairment (n = 41), Alzheimer's
      disease dementia (ADD; n = 35), frontotemporal dementia (FTD; n = 9), and
      cognitively healthy controls (HC; n = 21), using 10-fold cross-validation.
      METHODS: The combinations ranking in the top 10 according to diagnostic accuracy
      in differentiating between distinct diagnostic categories were identified.
      RESULTS: The single biomarkers or biomarker combinations generating the best area
      under the receiver operating characteristics (AUROCs) were the following: the
      combination [amyloid beta peptide + phosphorylated tau + neurofilament light
      chain] for distinguishing between ADD patients and HC (AUROC = 0.86), t-tau for
      distinguishing between ADD and FTD patients (AUROC = 0.82), and t-tau for
      distinguishing between FTD patients and HC (AUROC = 0.78). CONCLUSIONS: Novel and
      established cerebrospinal fluid markers perform with at least fair accuracy in
      the discrimination between ADD and FTD. The classification of mild cognitive
      impairment individuals was poor.

PMID- 29328926
TI  - DNA damage-associated oligodendrocyte degeneration precedes amyloid pathology and
      contributes to Alzheimer's disease and dementia.
AB  - INTRODUCTION: In looking for novel non-amyloid-based etiologies for Alzheimer's
      disease, we explore the hypothesis that age-related myelin loss is an attractive
      explanation for age-associated cognitive decline and dementia. METHODS: We
      performed a meta-analysis of data in the National Alzheimer's Coordinating Center
      database accompanied by quantitative histopathology of myelin and
      oligodendrocytes (OLs) in frontal cortices of 24 clinically characterized
      individuals. Pathological findings were further validated in an Alzheimer's
      disease mouse model and in culture. RESULTS: Myelin lesions increased with
      cognitive impairment in an amyloid-independent fashion with signs of degeneration
      appearing before neuronal loss. Myelinating OLs in the gray matter showed greater
      vulnerability than those in white matter, and the degenerative changes correlated
      with evidence of DNA damage. Similar results were found in myelinating OL
      cultures where DNA damage caused aberrant OL cell cycle re-entry and death.
      DISCUSSION: We present the first comprehensive analysis of the cell biology of
      early myelin loss in sporadic Alzheimer's disease.

PMID- 29328928
TI  - Driving cessation over a 24-year period: Dementia severity and cerebrospinal
      fluid biomarkers.
AB  - INTRODUCTION: With 36 million older adult U.S. drivers, safety is a critical
      concern, particularly among those with dementia. It is unclear at what stage of
      Alzheimer's disease (AD) older adults stop driving and whether preclinical AD
      affects driving cessation. METHODS: Time to driving cessation was examined based
      on Clinical Dementia Rating (CDR) and AD cerebrospinal fluid biomarkers. 1795
      older adults followed up to 24 years received CDR ratings. A subset (591) had
      cerebrospinal fluid biomarker measurements and was followed up to 17 years.
      Differences in CDR and biomarker groups as predictors of time to driving
      cessation were analyzed using Kaplan-Meier curves and Cox proportional models.
      RESULTS: Higher CDR scores and more abnormal biomarker measurements predicted a
      shorter time to driving cessation. DISCUSSION: Higher levels of AD biomarkers,
      including among individuals with preclinical AD, lead to earlier driving
      cessation. Negative functional outcomes of preclinical AD show a nonbenign phase
      of the disease.

PMID- 29328929
TI  - Eicosapentaenoic acid production from Nannochloropsis oceanica CY2 using deep sea
      water in outdoor plastic-bag type photobioreactors.
AB  - In this study, Nannochloropsis oceanica CY2 was grown in deep-sea water (DSW)
      based medium in 5-L plastic bag-type photobioreactors (PBRs) for the autotrophic
      production of Eicosapentaenoic acid (EPA, 20:5n-3). EPA production of N. oceanica
      CY2 was stimulated when it was grown in 100% DSW amended with 1.5 g L-1 NaNO3,
      achieving a EPA content of 3.1% and a biomass concentration of 3.3 g L-1. An
      outdoor-simulated microalgae cultivation system was also conducted to validate
      the feasibility of outdoor cultivation of the CY2 strain in plastic bag-type
      PBRs. Using an inoculum size of 0.6 g/L, the biomass concentration in the PBR
      culture was 3.5 g L-1, while the EPA content and productivity reached a maximal
      level of 4.12% and 7.49 mg L-1 d-1, respectively. When the PBRs were operated on
      semi-batch mode, the EPA productivity could further increase to 9.9 mg L-1 d-1
      with a stable EPA content of 4.1%.

PMID- 29328930
TI  - Enhanced treatment of petroleum refinery wastewater by short-term applied voltage
      in single chamber microbial fuel cell.
AB  - Electrochemically active anodic biofilm that has adapted under mild applied
      potentials in the range 100-500 mV was evaluated for its improved
      bioelectrogenesis and bioelectrochemical treatment of petroleum refinery
      wastewater (PRW) in a single chamber air cathode microbial fuel cell (MFC). MFC
      operation with 500 mV as supplemental voltage has exhibited a maximum power
      density of 132 mW/m2, which was three times higher than control MFC (45 mW/m2).
      Similarly, highest substrate removal efficiency (48%) was also obtained with the
      MFC of 500 mV, followed by 300 mV (37%), 100 mV (32%) and control (27%).
      Adaptation under applied potential conditions also exhibited enhanced degradation
      efficiency of diesel range organics (DROs)/straight chain-alkanes. The strategy
      efficiently reduced DROs with the maximum efficiency of 89% (500 mV), which is
      almost 50% higher than that of the control system (59%), demonstrating the
      effectiveness of using supplemented voltage in treating PRW.

PMID- 29328932
TI  - Effective algal harvesting by using mesh membrane for enhanced energy recovery in
      an innovative integrated photobioelectrochemical system.
AB  - In this work, an innovative design of integrated photobioelectrochemcial system
      (IPB) and an algal harvesting method based on polyester-mesh membrane (MM) were
      investigated. The algal growth/harvesting period of 6 days led to the highest
      surface biomass productivity (SBP) of 0.88 g m-2 day-1 and the highest energy
      generation of 0.157 +/- 0.001 kJ day-1. The harvesting frequency of 3 times in an
      operational cycle (with three pieces of MM) enhanced the SBP to 1.14 g m-2 day-1.
      The catholyte recirculation for catholyte mixing resulted in a positive net
      energy production (NEP) of 0.227 +/- 0.025 kJ day-1. Those results have
      demonstrated the benefits of both using mesh membrane and the new reactor design
      for algal collection with positive effects on improving IPB performance.

PMID- 29328931
TI  - Biostimulation and bioaugmentation of native microbial community accelerated
      bioremediation of oil refinery sludge.
AB  - Scope for developing an engineered bioremediation strategy for the treatment of
      hydrocarbon-rich petroleum refinery waste was investigated through biostimulation
      and bioaugmentation approaches. Enhanced (46-55%) total petroleum hydrocarbon
      (TPH) attenuation was achieved through phosphate, nitrate or nitrate+phosphate
      amendment in the sludge with increased (upto 12%) abundance of fermentative,
      hydrocarbon degrading, sulfate-reducing, CO2-assimilating and methanogenic
      microorganisms (Bacillus, Coprothermobacter, Rhodobacter, Pseudomonas,
      Achromobacter, Desulfitobacter, Desulfosporosinus, T78, Methanobacterium,
      Methanosaeta, etc). Together with nutrients, bioaugmentation with biosurfactant
      producing and hydrocarbon utilizing indigenous Bacillus strains resulted in 57
      75% TPH reduction. Phylogenetic Investigation of Communities by Reconstruction of
      Unobserved States (PICRUSt) analysis revealed enhanced gene allocation for
      transporters (0.45-3.07%), ABC transporters (0.38-2.07%), methane (0.16-1.06%),
      fatty acid (0.018-0.15%), nitrogen (0.07-0.17%), butanoate (0.06-0.35%),
      propanoate (0.004-0.26%) metabolism and some xenobiotics (0.007-0.13%)
      degradation. This study indicated that nutrient-induced community dynamics of
      native microorganisms and their metabolic interplay within oil refinery sludge
      could be a driving force behind accelerated bioremediation.

PMID- 29328933
TI  - Economic assessment of biodiesel production from wastewater sludge.
AB  - Currently, there are mainly two pathways of the biodiesel production from
      wastewater sludge including 1) directly extracting the lipid in sludge and then
      converting the lipid to biodiesel through trans-esterification, and 2) employing
      sludge as medium to cultivate oleaginous microorganism to accumulate lipid and
      then transferring the lipid to biodiesel. So far, the study was still in research
      stage and its cost feasibility was not yet investigated. In this study, biodiesel
      production from wastewater sludge was designed and the cost was estimated with
      SuperPro Designer. With consideration of converting the lipid in raw sludge to
      biodiesel, the unit production cost was 0.67 US $/kg biodiesel (0.59 US $/L
      biodiesel). When the sludge was used as medium to grow oleaginous microorganism
      to accumulate lipid for producing biodiesel, the unit production cost was 1.08 US
      $/kg biodiesel (0.94 US $/L biodiesel). The study showed that sludge has great
      potential in biodiesel production.

PMID- 29328934
TI  - Anaerobic co-digestion of coffee husks and microalgal biomass after thermal
      hydrolysis.
AB  - Residual coffee husks after seed processing may be better profited if
      bioconverted into energy through anaerobic digestion. This process may be
      improved by implementing a pretreatment step and by co-digesting the coffee husks
      with a more liquid biomass. In this context, this study aimed at evaluating the
      anaerobic co-digestion of coffee husks with microalgal biomass. For this, both
      substrates were pretreated separately and in a mixture for attaining 15% of total
      solids (TS), which was demonstrated to be the minimum solid content for
      pretreatment of coffee husks. The results showed that the anaerobic co-digestion
      presented a synergistic effect, leading to 17% higher methane yield compared to
      the theoretical value of both substrates biodegraded separately. Furthermore,
      thermal hydrolysis pretreatment increased coffee husks anaerobic
      biodegradability. For co-digestion trials, the highest values were reached for
      pretreatment at 120  degrees C for 60 min, which led to 196 mLCH4/gVS and maximum
      methane production rate of 0.38 d-1.

PMID- 29328935
TI  - Evaluation of robustness of activated sludge using calcium-induced enhancement of
      respiration.
AB  - Robustness of an activated sludge system, describing uncertainty and operational
      risk, was evaluated using the absence or presence of calcium-induced enhancement
      of respiration (CaER) effect. Generally, the fast-growing system was susceptible
      to external environmental variations, of which the sludge exhibited significant
      CaER effect under normal operational conditions, while the slow growing system
      showed less significant CaER effect. However, sludge in both systems exhibited
      CaER effect under stressed conditions of decreasing temperature or ammonia
      shocking. Therefore, the absence of CaER effect indicates a more robust system,
      while the presence of CaER effect indicates a susceptible system. Additionally, a
      method to identify safe and dangerous shocking was established by a hybrid usage
      of absence or presence of CaER effect and recovery index (RI) curve type. The
      evaluation of robustness could help determining when adjustment should be really
      taken to cope with the uncertainty, and thus holds a high promise for field
      application.

PMID- 29328936
TI  - Pyrolysis and reutilization of plant residues after phytoremediation of heavy
      metals contaminated sediments: For heavy metals stabilization and dye adsorption.
AB  - This study aimed to investigate the effect of pyrolysis on the stabilization of
      heavy metals in plant residues obtained after phytoremediation. Ramie residues,
      being collected after phytoremediation of metal contaminated sediments, were
      pyrolyzed at different temperatures (300-700  degrees C). Results indicated that
      pyrolysis was effective in the stabilization of Cd, Cr, Zn, Cu, and Pb in ramie
      residues by converting the acid-soluble fraction of metals into residual form and
      decreasing the TCLP-leachable metal contents. Meanwhile, the reutilization
      potential of using the pyrolysis products generated from ramie residues obtained
      after phytoremediation as sorbents was investigated. Adsorption experiments
      results revealed that the pyrolysis products presented excellent ability to
      adsorb methylene blue (MB) with a maximum adsorption capacity of 259.27 mg/g.
      This study demonstrated that pyrolysis could be used as an efficient alternative
      method for stabilizing heavy metals in plant residues obtained after
      phytoremediation, and their pyrolysis products could be reutilized for dye
      adsorption.

PMID- 29328937
TI  - Utilization of methanol in crude glycerol to assist lipid production in non
      sterilized fermentation from Trichosporon oleaginosus.
AB  - In this work, methanol in crude glycerol solution was used to assist the lipid
      production with oleaginous yeast Trichosporon oleaginosus cultivated under non
      sterilized conditions. The investigated methanol concentration was 0%, 1.4%,
      2.2%, 3.3% and 4.4% (w/v). The results showed that methanol played a significant
      role in the non-sterilized fermentation for lipid production. The optimal
      methanol concentration was around 1.4% (w/v) in which the growth of T.
      oleaginosus was promoted and overcame that of the contaminants. The non
      sterilized fed-batch fermentation with initial methanol concentration of 1.4%
      (w/v) was then performed and high biomass production (43.39 g/L) and lipid
      production (20.42 g/L) were achieved.

PMID- 29328938
TI  - Time course of inhibition of return in a spatial cueing paradigm with
      distractors.
AB  - Studies of endogenous and exogenous attentional orienting in spatial cueing
      paradigms have been used to investigate inhibition of return, a behavioral
      phenomenon characterized by delayed reaction time in response to recently
      attended locations. When eye movements are suppressed, attention is covertly
      oriented to central or peripheral stimuli. Overt orienting, on the other hand,
      requires explicit eye movements to the stimuli. The present study examined the
      time course of slowed reaction times to previously attended locations when
      distractors are introduced into overt and covert orienting tasks. In a series of
      experiments, manual responses were required to targets following central and
      peripheral cues at three different cue-target intervals, with and without
      activated oculomotor systems. The results demonstrate that, when eye movements
      are suppressed, behavioral inhibition is reduced or delayed in magnitude by the
      presence of a distractor relative to conditions without distractors. However, the
      time course of behavioral inhibition when eye movements are required remains
      similar with or without distractors.

PMID- 29328939
TI  - Outcome of patients with uterine fibroids after 3-month ulipristal acetate
      therapy.
AB  - OBJECTIVES: To determine the proportion and the characteristics of patients who
      did or did not respond after 3 months of ulipristal acetate (UPA) therapy. STUDY
      DESIGN: In this retrospective cohort study conducted in the University Hospital
      of Bordeaux (France) and University Medical Center Ljubljana (Slovenia),
      symptomatic non-menopausal patients with fibroids that qualified for surgery were
      pretreated by 3 months of oral UPA 5 mg/day. Clinical success was defined by
      normalization of the bleeding score, and/or regression of pelvic pain, and/or
      abdominal distension. Imaging success was defined by reduction in fibroid volume
      >= 25%. RESULTS: The clinical and imaging success rates were 54/66 (82%) and
      39/66 (59%) respectively. The absence of previous pregnancy (p = 0.004) and the
      size of the dominant fibroid >= 80 mm (p = 0.004) were independent factors
      associated with clinical failure. Age <35 years (p = 0.02) was the only
      independent factor associated with imaging failure. CONCLUSION: Young women
      developing fibroids and/or women with large fibroids may be resistant to
      ulipristal acetate therapy.

PMID- 29328940
TI  - First trimester serum biomarkers to predict gestational diabetes in a high-risk
      cohort: Striving for clinically useful thresholds.
AB  - OBJECTIVES: Screening and diagnosis of gestational diabetes (GDM) has been a
      source of controversy. The prevalence has increased in line with an obesity
      epidemic and a trend towards delayed child-bearing. Treatment of even modest
      glycaemic impairment in pregnancy has been shown to be beneficial in preventing
      its clinical sequalae. However the cumbersome nature and timing of the oral
      glucose tolerance test coupled with debate around universal versus risk factor
      based screening have been problematic. This group aimed to investigate a panel of
      biomarkers which have shown promise in the literature to predict GDM from the
      first trimester in a group of high risk women. METHODS: Serum samples were drawn
      on 248 women deemed at risk of GDM before 15 weeks' gestation to measure C
      reactive protein, sex hormone binding globulin, adiponectin and 1,5
      anhydroglucitol. Patients underwent an oral glucose tolerance test as per IADPSG
      criteria at 28 weeks' gestation. Multiple logistic regression was used to examine
      the link between incidence of GDM and early pregnancy serum biomarkers. RESULTS:
      Adiponectin levels in the first trimester are independently linked to the risk of
      GDM. Serum adiponectin <8.9 MUg/ml gives an odds ratio of 3.3 for GDM.Mean 1,5 AG
      levels are significantly lower in those that go on to develop GDM. SHBG levels
      measured in the first trimester were linked to the risk of GDM. However, this was
      no longer statistically significant once BMI, ethnicity and family history were
      taken into consideration. First trimester measurement of CRP is not a useful
      indicator of GDM risk. CONCLUSIONS: First trimester measurement of Adiponectin
      and 1,5 Anhydroglucitol are potential early biomarkers for the later onset of
      GDM. Risk stratification using these biomarkers may facilitate early diagnosis
      and management of GDM to mitigate against its complications.

PMID- 29328941
TI  - Production of mono- to few-layer MoS2 nanosheets in isopropanol by a salt
      assisted direct liquid-phase exfoliation method.
AB  - Here, we report a facile salt-assisted direct liquid-phase exfoliation method for
      mass production of MoS2 nanosheets. We choose organic solvent isopropanol (IPA)
      as exfoliation media and potassium ferrocyanide, potassium sodium tartrate, or
      sodium tartrate as salt, the assistant. The selected salts show universal and
      efficient assistant effect for the exfoliation of MoS2 in IPA. Especially,
      potassium ferrocyanide (K4Fe(CN)6) can enhance the exfoliation efficiency up to
      73 times and a dispersion of MoS2 nanosheets with concentration as high as 0.240
      mg mL-1 can be easily obtained in IPA-K4Fe(CN)6 system. Transmission electron
      microscopy, atomic force microscopy (AFM), and Raman spectroscopy show that bulk
      MoS2 has been successfully exfoliated into mono- to few-layer MoS2 nanosheets.
      AFM analysis indicates that nearly 60% flakes are monolayer in MoS2 dispersion.

PMID- 29328942
TI  - Contact angle hysteresis effect on the thermocapillary migration of liquid
      droplets.
AB  - Thermocapillary migration describes a phenomenon where a liquid droplet spreads
      from warm to cold regions due to the interfacial tension gradients. Since the
      contact angle hysteresis effect is involved during the migration process, we
      consider the hysteresis effect and rectify the theoretical model to predict the
      migration velocity on solid surfaces. By conducting migration experiments on
      surfaces with different magnitudes of the hysteresis effect, we verify the
      validity of the theoretical derivation. This study advances the understanding of
      the interfacial phenomenon of thermocapillary migration, moreover, offers an
      insight into the migration capacity of different materials and guides the design
      of key components associated with the thermal gradients.

PMID- 29328943
TI  - Interval breast cancers in the 'screening with tomosynthesis or standard
      mammography' (STORM) population-based trial.
AB  - BACKGROUND & METHODS: The prospective 'screening with tomosynthesis or standard
      mammography' (STORM) trial recruited women participating in biennial breast
      screening in Italy (2011-2012), and compared sequential screen-readings based on
      2D-mammography alone or based on tomosynthesis (integrated 2D/3D-mammography).
      The STORM trial showed that tomosynthesis screen-reading significantly increased
      breast cancer detection compared to 2D-mammography alone. The present study
      completes reporting of the trial by examining interval breast cancers ascertained
      at two year follow-up. RESULTS: 9 interval breast cancers were identified; the
      estimated interval cancer rate was 1.23/1000 screens [9/7292] (95%CI 0.56 to
      2.34) or 1.24/1000 negative screens [9/7235] (95%CI 0.57 to 2.36). In
      concurrently screened women who attended the same screening services and received
      2D-mammography, interval cancer rate was 1.60/1000 screens [40/25,058] (95% CI
      1.14 to 2.17) or 1.61/1000 negative screens [40/24,922] (95% CI 1.15 to 2.18).
      Estimated screening sensitivity for the STORM trial was 85.5% [59/69] (95%CI
      75.0%-92.8%), and that for 2D-mammography screening was 77.3% [136/176] (95%CI
      70.4%-83.2%). CONCLUSION: Interval breast cancer rate amongst screening
      participants in the STORM trial was marginally lower (and screening sensitivity
      higher) than estimates amongst 2D-screened women; these findings should be
      interpreted with caution given the small number of interval cases and the sample
      size of the trial. Much larger screening studies, or pooled analyses, are
      required to examine interval cancer rates arising after breast tomosynthesis
      screening versus digital mammography screening.

PMID- 29328944
TI  - Analysis of the evolution of gross alpha and gross beta activities in airborne
      samples in Valencia (Spain).
AB  - Gross alpha (Aalpha) and gross beta activities (Abeta) were measured weekly in
      the airborne of the Universitat Politecnica de Valencia campus (in the east of
      Spain) during the period 2009-2015 (7 years). The geometric mean values of weekly
      Aalpha and Abeta were 0.53.10-4 Bq m-3 and 5.77.10-4 Bq m-3, respectively; with
      an average ratio Aalpha/Abeta of 0.097. This study highlights the heterogeneity
      of gross alpha and gross beta activities depending on the different periods of
      the year. Data show seasonal variations with the highest activity in summer
      months and the lowest one in winter months. Several atmospheric factors were
      considered in order to explain this intra-annual variation (wind speed,
      temperature, relative humidity, precipitations, dust content and prevailing wind
      directions). Multiple Linear Regression Analysis were performed in order to
      obtain information on significant atmospheric factors that affect gross alpha and
      gross beta variability, which could be useful in identifying meteorological or
      atmospheric changes that could cause deviations in gross alpha and gross beta
      activity depending on the seasons considered. Models obtained explain more than
      60% of variability for global data, and also for winter and spring-autumn months.
      However, more research is needed to explain gross alpha and gross beta
      variability in summer months, because the atmospheric factors considered in the
      MLR explain less than 35% of variability.

PMID- 29328945
TI  - Astaxanthin ameliorates cerulein-induced acute pancreatitis in mice.
AB  - BACKGROUND: A various of pharmacological effects of astaxanthin has been
      confirmed. However, the mechanism underlying protective effect of astaxanthin on
      acute pancreatitis (AP) induced by cerulein still unclear. The present study is
      to investigate the mechanism underlying the effect of astaxanthin on autophagy
      and apoptosis via the JAK/STAT3 pathway. METHODS: Intraperitoneal injection of
      cerulein at hourly intervals followed by lipopolysaccharide injection were used
      in Balb/C mice. Vehicle or astaxanthin, which intraperitoneal injected in two
      doses (20 mg/kg and 40 mg/kg), were injected in mice 1 h before the first
      cerulein injection. At 3 h after the last injection, when the pathological
      changes were most severe, pancreatic tissue was analyzed by pathologically scored
      and hematoxylin and eosin (H&E) staining. The severity of AP was assessed by
      histological grading, proinflammatory cytokine levels, biochemistry,
      myeloperoxidase (MPO) activity, and analysis of JAK/STAT3 activity. RESULTS:
      Astaxanthin administration markedly reduced serum digestive enzyme activities,
      pancreatic histological scores, proinflammatory cytokine levels (tumor necrosis
      factor-alpha (TNF-alpha), Interleukin-1beta (IL-1beta), and Interleukin-6 (IL
      6)), MPO and JAK/STAT3 activity. CONCLUSION: Collectively, these results indicate
      that astaxanthin inhibits pancreatic injury in AP by targeting JAK/STAT3-mediated
      apoptosis and autophagy.

PMID- 29328946
TI  - Kaempferol alleviates LPS-induced neuroinflammation and BBB dysfunction in mice
      via inhibiting HMGB1 release and down-regulating TLR4/MyD88 pathway.
AB  - Kaempferol is a natural flavonoid with many biological activities including anti
      oxidation and anti-inflammation. Nevertheless, its anti-neuroinflammation role
      and the relevant mechanism remain unclear. The present study was to investigate
      effects of kaempferol against LPS-induced neuroinflammation and blood-brain
      barrier dysfunction as well as the mechanism in mice. BALB/c mice were treated
      with LPS 5mg/kg to induce inflammation after pre-treatment with kaempferol 25,
      50, or 100mg/kg for 7days. The results showed that kaempferol reduced the
      production of various pro-inflammatory factors and inflammatory proteins
      including IL-1beta, IL-6, TNF-alpha, MCP-1, COX-2 and iNOS in brain tissues. In
      addition, kaempferol also protected BBB integrity and increased BBB related
      proteins including occludin-1, claudin-1 and CX43 in brain of LPS-induced mice.
      Furthermore, kaempferol significantly reduced HMGB1 level and suppressed
      TLR4/MyD88 inflammatory pathway in both transcription level and translation
      level. These results collectively suggested that kaempferol might be a promising
      neuroprotective agent for alleviating inflammatory responses and BBB dysfunction
      by inhibiting HMGB1 release and down-regulating TLR4/MyD88 inflammatory pathway.

PMID- 29328947
TI  - Evaluating the role of repetitive negative thinking in the maintenance of social
      appearance anxiety: An experimental manipulation.
AB  - Social appearance anxiety (SAA), or fear of having one's appearance negatively
      evaluated by others, is a risk factor for eating pathology and social anxiety,
      but maintenance processes for SAA remain unclear. The current study evaluated
      repetitive negative thinking (RNT) as a process through which SAA is maintained
      over time. Undergraduates (N = 126) completed self-report measurements, made an
      impromptu speech task to induce SAA, and were randomized to either engage in RNT
      or distraction following the speech task. Participants then attended a second
      appointment one day later and were asked to make a second speech. Results
      indicated positive associations between self-reported trait SAA and RNT.
      Individuals asked to engage in RNT following the appointment 1 speech task
      reported significantly higher state SAA than those who engaged in distraction.
      Findings indicated no significant effect of group on appointment 2 SAA, but post
      hoc analyses suggested that naturally-occurring RNT may have accounted for
      increases in SAA across appointments. Overall, results provide support for the
      importance of RNT in maintaining various internalizing symptoms.

PMID- 29328948
TI  - Psychopathology and episodic future thinking: A systematic review and meta
      analysis of specificity and episodic detail.
AB  - Episodic future thinking (EFT) refers to the mental simulation of future events
      that might be personally-experienced; a crucial mental process in adaptation.
      Psychiatric disorders are associated with deficits in recalling episodic memory,
      however, no study has reviewed the empirical literature to assess for similar
      deficits in EFT. A systematic review comparing psychiatric groups with control
      groups on the specificity and episodic detail of EFT returned 19 eligible
      studies. An overall effect of g = -0.84 (95%CI = -1.06, - 0.62, p < .001)
      indicated individuals with a psychiatric diagnosis have significantly less
      specific and detailed EFT. Publication bias was not detected, but heterogeneity
      was. No methodological characteristics were significant moderators. Subgroup
      analyses showed significant effects for depression (g = -0.79, p < .001, k = 7),
      bipolar disorder (g = -1.00, p < .001, k = 2), and schizophrenia (g = -1.06, p <
      .001, k = 6), but not posttraumatic stress disorder (g = -1.04, p = .260, k = 2)
      or complicated grief (g = -0.41, p = .08, k = 2). Deficits in EFT are apparent in
      some psychiatric disorders. However, many clinical groups are understudied, and
      the causal mechanisms and remediation of these deficits require further research
      attention.

PMID- 29328949
TI  - Conditionals and inferential connections: A hypothetical inferential theory.
AB  - Intuition suggests that for a conditional to be evaluated as true, there must be
      some kind of connection between its component clauses. In this paper, we
      formulate and test a new psychological theory to account for this intuition. We
      combined previous semantic and psychological theorizing to propose that the key
      to the intuition is a relevance-driven, satisficing-bounded inferential
      connection between antecedent and consequent. To test our theory, we created a
      novel experimental paradigm in which participants were presented with a soritical
      series of objects, notably colored patches (Experiments 1 and 4) and spheres
      (Experiment 2), or both (Experiment 3), and were asked to evaluate related
      conditionals embodying non-causal inferential connections (such as "If patch
      number 5 is blue, then so is patch number 4"). All four experiments displayed a
      unique response pattern, in which (largely determinate) responses were sensitive
      to parameters determining inference strength, as well as to consequent position
      in the series, in a way analogous to belief bias. Experiment 3 showed that this
      guaranteed relevance can be suppressed, with participants reverting to the
      defective conditional. Experiment 4 showed that this pattern can be partly
      explained by a measure of inference strength. This pattern supports our theory's
      "principle of relevant inference" and "principle of bounded inference,"
      highlighting the dual processing characteristics of the inferential connection.

PMID- 29328950
TI  - Ultrastructural damage in Streptococcus mutans incubated with saliva and histatin
      5.
AB  - OBJECTIVE: To study the ultrastructural alterations induced in Streptococcus
      mutans (ATCC 25175) incubated with saliva, saliva plus histatin 5 and histatin 5.
      METHODS: S. mutans incubated with saliva histatin 5 or a combination of both were
      morphologically analyzed and counted. The results were expressed as (CFU)ml-1.
      Ultrastructural damage was evaluated by transmission electron microscopy.
      Ultrastructural localization of histatin 5 was examined using immunogold
      labeling. Apoptotic cell death was determined by flow cytometry (TUNEL). RESULTS:
      A decrease in the bacteria numbers was observed after incubation with saliva,
      saliva with histatin 5 or histatin 5 compared to the control group (p<0.0001).
      Ultrastructural damage in S. mutans incubated with saliva was found in the cell
      wall. Saliva plus histatin 5 induced a cytoplasmic granular pattern and decreased
      the distance between the plasma membrane bilayers, also found after incubation
      with histatin 5, together with pyknotic nucleoids. Histatin 5 was localized on
      the bacterial cell walls, plasma membranes, cytoplasm and nucleoids. Apoptosis
      was found in the bacteria incubated with saliva (63.9%), saliva plus histatin 5
      (71.4%) and histatin 5 (29.3%). Apoptosis in the control bacteria was 0.2%.
      CONCLUSIONS: Antibacterial activity against S. mutans and the morphological
      description of damage induced by saliva and histatin 5 was demonstrated. Pyknotic
      nucleoids observed in S. mutans exposed to saliva, saliva plus histatin 5 and
      histatin 5 could be an apoptosis-like death mechanism. The knowledge of the
      damage generated by histatin 5 and its intracellular localization could favor the
      design of an ideal peptide as a therapeutic agent.

PMID- 29328952
TI  - Synthesis, structures and photophysical properties of two regioisomeric
      phenalenocarbazoles.
AB  - Two regioisomeric phenalenocarbazoles have been synthesized by direct reductive
      cyclization of 2'-Nitrophenyl-pyrene isomers respectively. Their photophysical
      properties and crystal structures as well as CV properties were investigated and
      compared with those of sulfur containing analogues. Although the fluorescence
      emission properties of 1N are very similar with those of 2N, the HOMO energy
      level of 1N is 0.16eV higher than that of 2N indicating that 1N has better
      electron donating ability.

PMID- 29328951
TI  - Epoxy matrix with triaromatic mesogenic unit in dielectric spectroscopy
      observation.

PMID- 29328953
TI  - The binding interaction of imazapyr with cucurbit[n]uril (n=6-8): Combined
      experimental and molecular modeling study.
AB  - The inclusion complexes of imazapyr (IMA) with cucurbit[n]uril, CB[n] (n=6-8),
      have been investigated. Fluorescence spectroscopy, MALDI-TOF, and 1HNMR were used
      to investigate and characterize the inclusion complexation of IMA and CB[n] in
      solutions. Whereas the solid state complexes have been characterized by Fourier
      transform infrared spectroscopy (FTIR), and powder X-ray diffraction (PXRD). IMA
      was found to form 1:1 complexes with CB[n] with association constants ranging
      from 5.80*102-2.65*103. The guest molecule IMA was found to encapsulate into the
      larger cavities of CB[7] and CB[8], whereas with CB[6] the molecule remains
      outside the cavity. Molecular dynamic (MD) simulations were used to follow the
      inclusion process at an atomistic level to study the mechanism and stability of
      inclusion. The results obtained showed that inclusion complexes of IMA with both
      CB[7] and CB[8] are highly stable in aqueous media, but the CB[6] smaller cavity
      size prohibited the formation of an inclusion complex with IMA. The results
      clearly show that in addition to hydrophobic effects the presence of hydrogen
      bonding has added greatly to the stability of these complexes.

PMID- 29328955
TI  - Investigation of carbonates in the Sutter's Mill meteorite grains with
      hyperspectral infrared imaging micro-spectroscopy.
AB  - Synchrotron-based high spatial resolution hyperspectral infrared imaging
      technique provides thousands of infrared spectra with high resolution, thus
      allowing us to acquire detailed spatial maps of chemical molecular structures for
      many grains in short times. Utilizing this technique, thousands of infrared
      spectra were analyzed at once instead of inspecting each spectrum separately.
      Sutter's Mill meteorite is a unique carbonaceous type meteorite with highly
      heterogeneous chemical composition. Multiple grains from the Sutter's Mill
      meteorite have been studied using this technique and the presence of both hydrous
      and anhydrous silicate minerals have been observed. It is observed that the
      carbonate mineralogy varies from simple to more complex carbonates even within a
      few microns in the meteorite grains. These variations, the type and distribution
      of calcite-like vs. dolomite-like carbonates are presented by means of
      hyperspectral FTIR imaging spectroscopy with high resolution. Various scenarios
      for the formation of different carbonate compositions in the Sutter's Mill parent
      body are discussed.

PMID- 29328954
TI  - Probing the stereoselective interaction of ofloxacin enantiomers with
      corresponding monoclonal antibodies by multiple spectrometry.
AB  - Although stereoselective antibody has immense potential in chiral compounds
      detection and separation, the interaction traits between stereoselective antibody
      and the corresponding antigenic enantiomers are not yet fully exploited. In this
      study, the stereospecific interactions between ofloxacin isomers and
      corresponding monoclonal antibodies (McAb-WR1 and McAb-MS1) were investigated
      using time-resolved fluorescence, steady-state fluorescence, and circular
      dichroism (CD) spectroscopic methods. The chiral recognition discrepancies of
      antibodies with ofloxacin isomers were reflected through binding constant, number
      of binding sites, driving forces and conformational changes. The major
      interacting forces of McAb-WR1 and McAb-MS1 chiral interaction systems were
      hydrophobic force and van der Waals forces joined up with hydrogen bonds,
      respectively. Synchronous fluorescence spectra and CD spectra results showed that
      the disturbing of tyrosine and tryptophan micro-environments were so slightly
      that no obvious secondary structure changes were found during the chiral hapten
      binding. Clarification of stereospecific interaction of antibody will facilitate
      the application of immunoassay to analyze chiral contaminants in food and other
      areas.

PMID- 29328956
TI  - Predicting post-breakup distress and growth in emerging adulthood: The roles of
      relationship satisfaction and emotion regulation.
AB  - With a sample of emerging adults (N = 110; 72% female) this brief report utilized
      self-report measures to examine the role of relationship satisfaction and emotion
      regulation strategies assessed at age 20 in predicting breakup distress and
      posttraumatic growth three years later. Results showed that higher relationship
      satisfaction is associated with less future breakup distress. Emotion regulation
      explained the ways individuals cope with distress; cognitive appraisal (in
      contrast to emotional suppression) predicted higher growth after experiencing a
      breakup. Findings highlight the ways emotion regulation strategies can help
      emerging adults cope with relational stressors such as breakups.

PMID- 29328957
TI  - Sphingolipids in host-microbial interactions.
AB  - Sphingolipids, a lipid class characterized by a long-chain amino alcohol
      backbone, serve vital structural and signaling roles in eukaryotes. Though
      eukaryotes produce sphingolipids, this capacity is phylogenetically highly
      restricted in Bacteria. Intriguingly, bacterial species commonly associated in
      high abundance with eukaryotic hosts include sphingolipid producers, such as the
      Bacteroidetes in the mammalian gut. To date, a role for bacterial sphingolipids
      in immune system maturation has been described, but their fate and impact in host
      physiology and metabolism remain to be elucidated. The structural conservation of
      bacterial sphingolipids with those produced by their mammalian hosts offer clues
      about which aspects of mammalian biology may be modulated by these intriguing
      lipids.

PMID- 29328958
TI  - STDP-based spiking deep convolutional neural networks for object recognition.
AB  - Previous studies have shown that spike-timing-dependent plasticity (STDP) can be
      used in spiking neural networks (SNN) to extract visual features of low or
      intermediate complexity in an unsupervised manner. These studies, however, used
      relatively shallow architectures, and only one layer was trainable. Another line
      of research has demonstrated - using rate-based neural networks trained with back
      propagation - that having many layers increases the recognition robustness, an
      approach known as deep learning. We thus designed a deep SNN, comprising several
      convolutional (trainable with STDP) and pooling layers. We used a temporal coding
      scheme where the most strongly activated neurons fire first, and less activated
      neurons fire later or not at all. The network was exposed to natural images.
      Thanks to STDP, neurons progressively learned features corresponding to
      prototypical patterns that were both salient and frequent. Only a few tens of
      examples per category were required and no label was needed. After learning, the
      complexity of the extracted features increased along the hierarchy, from edge
      detectors in the first layer to object prototypes in the last layer. Coding was
      very sparse, with only a few thousands spikes per image, and in some cases the
      object category could be reasonably well inferred from the activity of a single
      higher-order neuron. More generally, the activity of a few hundreds of such
      neurons contained robust category information, as demonstrated using a classifier
      on Caltech 101, ETH-80, and MNIST databases. We also demonstrate the superiority
      of STDP over other unsupervised techniques such as random crops (HMAX) or auto
      encoders. Taken together, our results suggest that the combination of STDP with
      latency coding may be a key to understanding the way that the primate visual
      system learns, its remarkable processing speed and its low energy consumption.
      These mechanisms are also interesting for artificial vision systems, particularly
      for hardware solutions.

PMID- 29328959
TI  - Impact of individual and neighborhood factors on disparities in prostate cancer
      survival.
AB  - BACKGROUND: We addressed the hypothesis that individual-level factors act jointly
      with social and built environment factors to influence overall survival for men
      with prostate cancer and contribute to racial/ethnic and socioeconomic (SES)
      survival disparities. METHODS: We analyzed multi-level data, combining (1)
      individual-level data from the California Collaborative Prostate Cancer Study, a
      population-based study of non-Hispanic White (NHW), Hispanic, and African
      American prostate cancer cases (N = 1800) diagnosed from 1997 to 2003, with (2)
      data on neighborhood SES (nSES) and social and built environment factors from the
      California Neighborhoods Data System, and (3) data on tumor characteristics,
      treatment and follow-up through 2009 from the California Cancer Registry.
      Multivariable, stage-stratified Cox proportional hazards regression models with
      cluster adjustments were used to assess education and nSES main and joint effects
      on overall survival, before and after adjustment for social and built environment
      factors. RESULTS: African American men had worse survival than NHW men, which was
      attenuated by nSES. Increased risk of death was associated with residence in
      lower SES neighborhoods (quintile 1 (lowest nSES) vs. 5: HR = 1.56, 95% CI: 1.11
      2.19) and lower education (<high school vs. college: HR = 1.32, 95% CI: 1.05
      1.67), and a joint association of low education and low nSES was observed.
      Adjustment for behavioral, hospital, and restaurant and food environment
      characteristics only slightly attenuated these associations between SES and
      survival. CONCLUSION: Both individual- and contextual-level SES influence overall
      survival of men with prostate cancer. Additional research is needed to identify
      the mechanisms underlying these robust associations.

PMID- 29328960
TI  - The unusual suspects: A review of unusual benign and malignant male breast
      imaging cases.
AB  - Male breast disease is uncommon. Men presenting with breast symptoms may
      represent unique diagnostic challenges for the radiologist, particularly if
      imaging findings are not classic for gynecomastia or carcinoma. In this paper we
      review 10 unusual male breast cases, 5 benign and 5 malignant, including the
      radiologic findings, differential diagnosis, pathology and management.

PMID- 29328961
TI  - Vaginal delivery-related changes in the pelvic organ position and vaginal cross
      sectional area in the general population.
AB  - PURPOSE: Evaluate the effect of vaginal delivery on pelvic organ positions and
      vaginal cross-sectional areas. METHODS: MRI of 119 premenopausal women were
      grouped according to the number of deliveries. The distances from the three 3
      reference points (bladder, uterus, and rectum) to two 2-lines (pubococcygeal-line
      (PCL) and midpubic-line (MPL)), length of H- and M-lines and vaginal cross
      sectional area were compared between the groups. RESULTS: With increasing parity,
      distance from the rectum to PCL tended to increase (nullipara vs. bipara;
      p<0.01). Vaginal cross-sectional area was larger in bipara and tripara than in
      nullipara (p<0.01). CONCLUSIONS: Rectal position is more caudally located and
      vaginal cross-sectional area is larger in bipara than in nullipara.

PMID- 29328962
TI  - So you think computational approaches to understanding glycosaminoglycan-protein
      interactions are too dry and too rigid? Think again!
AB  - Glycosaminoglycans (GAGs) play key roles in virtually all biologic responses
      through their interaction with proteins. A major challenge in understanding these
      roles is their massive structural complexity. Computational approaches are
      extremely useful in navigating this bottleneck and, in some cases, the only
      avenue to gain comprehensive insight. We discuss the state-of-the-art on
      computational approaches and present a flowchart to help answer most basic, and
      some advanced, questions on GAG-protein interactions. For example, firstly, does
      my protein bind to GAGs?; secondly, where does the GAG bind?; thirdly, does my
      protein preferentially recognize a particular GAG type?; fourthly, what is the
      most optimal GAG chain length?; fifthly, what is the structure of the most
      favored GAG sequence?; and finally, is my GAG-protein system 'specific', 'non
      specific', or a combination of both? Recent advances show the field is now poised
      to enable a non-computational researcher perform advanced experiments through the
      availability of various tools and online servers.

PMID- 29328963
TI  - The effect of white matter hyperintensities on cognition is mediated by cortical
      atrophy.
AB  - White matter hyperintensities (WMH) have been linked to cognitive dysfunction and
      dementia, although the reasons are unclear. One possibility is that WMH promote
      neurodegeneration, which, in turn, affects cognition. We examined whether
      cortical thickness, a marker of neurodegeneration, mediates the relationship
      between WMH and cognition among 519 older adults. Using conditional process
      analysis modeling techniques, we examined the association between WMH volume and
      global cognition and tested whether cortical thickness mediates this relationship
      statistically. We also tested specific regional hypotheses to determine whether
      cortical thickness or volume in the medial temporal lobe mediates the
      relationship between WMH volume and memory. Increased total WMH volume was
      associated with poorer global cognition and memory. Global cortical thickness and
      medial temporal lobe thickness/volume mediated the relationship of WMH volume on
      global cognition and memory functioning. The mediating relationship was similar
      across racial and ethnic groups and across diagnostic groups (i.e., mild
      cognitive impairment/Alzheimer's disease). The findings suggest that WMH promote
      atrophy, which, in turn, drives cognitive decline and highlight a potential
      pathway in which small vessel cerebrovascular disease affects cognition by
      promoting neurodegenerative changes directly.

PMID- 29328965
TI  - Excited delirium syndrome after withdrawal from 10 days long recreationally used
      GHB.
AB  - We describe a case of a 51-year old man who used GHB only in the afternoon and
      evening during 10 consecutive days in a recreational way: 20 ml a day in 4 ml per
      2-3 hrs. He developed an excited delirium syndrome at the second day after
      stopping. Apparently even after relatively short recreational use severe
      disruptive behavior can develop. This is a unique case in literature. References
      are provided.

PMID- 29328964
TI  - A European multicenter study on the analytical performance of the VERIS HBV
      assay.
AB  - BACKGROUND: Hepatitis B viral load monitoring is an essential part of managing
      patients with chronic Hepatits B infection. Beckman Coulter has developed the
      VERIS HBV Assay for use on the fully automated Beckman Coulter DxN VERIS
      Molecular Diagnostics System.1 OBJECTIVES: To evaluate the analytical performance
      of the VERIS HBV Assay at multiple European virology laboratories. STUDY DESIGN:
      Precision, analytical sensitivity, negative sample performance, linearity and
      performance with major HBV genotypes/subtypes for the VERIS HBV Assay was
      evaluated. RESULTS: Precision showed an SD of 0.15 log10 IU/mL or less for each
      level tested. Analytical sensitivity determined by probit analysis was between
      6.8-8.0 IU/mL. Clinical specificity on 90 unique patient samples was 100.0%.
      Performance with 754 negative samples demonstrated 100.0% not detected results,
      and a carryover study showed no cross contamination. Linearity using clinical
      samples was shown from 1.23-8.23 log10 IU/mL and the assay detected and showed
      linearity with major HBV genotypes/subtypes. CONCLUSIONS: The VERIS HBV Assay
      demonstrated comparable analytical performance to other currently marketed assays
      for HBV DNA monitoring.

PMID- 29328966
TI  - Cementum as a source of DNA in challenging forensic cases.
AB  - Each forensic case is characterized by its own uniqueness. Deficient forensic
      cases require additional sources of human identifiers to assure the identity. We
      report on two different cases illustrating the role of teeth in answering
      challenging forensic questions. The first case involves identification of an
      adipocere male found in a car submersed in water for approximately 2 years. The
      second scenario, which involves paternity DNA testing of an exhumed body, was
      performed approximately 2.8 years post-mortem. The difficulty in anticipating the
      degradation of the DNA is one of the main obstacles. DNA profiling of dental
      tissues, DNA quantification by using real-time PCR (PowerQuantTM System/Promega)
      and a histological dental examination have been performed to address the
      encountered impediments of adverse post-mortem changes. Our results demonstrate
      that despite the adverse environmental conditions, a successful STR profile of
      DNA isolated from the root of teeth can be generated with respect to tooth type
      and apportion. We conclude that cementocytes are a fruitful source of DNA.
      Cementum resists DNA degradation in comparison to other tissues with respect to
      the intra- and inter-individual variation of histological and anatomical
      structures.

PMID- 29328967
TI  - Mycotoxin production of Alternaria strains isolated from Korean barley grains
      determined by LC-MS/MS.
AB  - Twenty-four Alternaria strains were isolated from barley grain samples. These
      strains were screened for the production of mycotoxins on rice medium using thin
      layer chromatography. All 24 strains produced at least one of the five mycotoxins
      (ALT, AOH, ATX-I, AME, and TeA). Three representative strains, namely EML-BLDF1
      4, EML-BLDF1-14, and EML-BLDF1-18, were further analyzed using a new LC-MS/MS
      based mycotoxin quantification method. This method was used to detect and
      quantify Alternaria mycotoxins. We used positive ion electrospray mass
      spectrometry with multiple reaction mode (MRM) for the simultaneous
      quantification of various Alternaria mycotoxins produced by these strains. Five
      Alternaria toxins (ALT, ATX-I, AOH, AME, and TeA) were detected and quantified.
      Sample preparation included methanol extraction, concentration, and injection
      into LC-MS/MS. Limit of detection ranged from 0.13 to 4MUg/mL and limit of
      quantification ranged from 0.25 to 8MUg/mL.

PMID- 29328968
TI  - In vitro examination of an oleosome-based sun protection product on the influence
      of UVB-induced inflammation markers in human epidermal skin equivalent tissue
      model.
AB  - In vitro human epidermal skin equivalent tissues (MatTek EpiDermTM) were employed
      to examine the influence of UVB radiation on various established inflammation
      markers in the presence of topically applied sunscreens. MatTek EpiDermTM tissues
      were treated with 2.0mg/cm2 of an Experimental oleosome-based SPF 30 product or a
      commercial SPF 30 beach product. Tissues were irradiated with 300mJ/cm2 of UVB
      radiation. Inflammatory cytokines IL-1alpha, IL-6 and IL-8 as well as arachidonic
      acid cascade marker PGE2 were examined via ELISA-based antibody detection.
      Untreated tissues irradiated with 300mJ/cm2 of UVB radiation showed statistically
      significant upregulation of IL-1alpha, IL-6 and IL-8 as well as PGE2. Application
      of both the experimental oleosome-based SPF 30 formulation and the commercial SPF
      30 formulation demonstrated an ability to prevent the upregulation of all four
      markers when applied prior to irradiation. The experimental oleosome-based SPF 30
      product contained approximately 80% less sunscreen actives than the commercial
      formulation. This study demonstrates that in vitro reconstructed human tissues
      can be used to study the influences of sun screen actives in the presence of UVB
      radiation. The results support previously reported clinical results that
      demonstrated that oleosome-based sun care formulations can function with high
      protection effects with significantly less sun care actives.

PMID- 29328969
TI  - Poly(3,6-diamino-9-ethylcarbazole) based molecularly imprinted polymer sensor for
      ultra-sensitive and selective detection of 17-beta-estradiol in biological
      fluids.
AB  - In this work, we reported the synthesis of 3, 6-diamino-9-ethylcarbazole and its
      application as a new monomer for preparation of molecularly imprinted polymer
      (MIP) electrochemical sensor. The as prepared MIP sensor exhibited ultrahigh
      sensitivity and selectivity for the detection of 17-beta-estradiol in attomolar
      levels (1 * 10-18molL-1). The sensor works by detecting the change of the
      interfacial impedance that is derived from recognition of 17-beta-estradiol on
      the MIP layer. The MIP sensor based on 3, 6-diamino-9-ethylcarbazole monomer
      revealed better performance than that of unmodified carbazole monomer. The
      monomer/template ratio, electropolymerization scanning cycles, and the incubation
      pH values were optimised in order to obtain the best detection efficiency. Under
      the optimised condition, the MIP sensor exhibits a wide linear range from 1aM to
      10MUM (1 * 10-18  1 * 10-5molL-1). A low detection limit of 0.36aM (3.6 * 10
      19molL-1) and a good selectivity towards structurally similar compounds were
      obtained. The proposed MIP sensor also exhibits long-term stability and
      applicability in human serum samples. These advantages enabled this MIP sensor to
      be a promising alternative of electrochemical sensor and may be extended to
      detection of other endogenous compounds.

PMID- 29328970
TI  - Spore-based biosensor to monitor the microbicidal efficacy of gaseous hydrogen
      peroxide sterilization processes.
AB  - In this work, a spore-based biosensor is evaluated to monitor the microbicidal
      efficacy of sterilization processes applying gaseous hydrogen peroxide (H2O2).
      The sensor is based on interdigitated electrode structures (IDEs) that have been
      fabricated by means of thin-film technologies. Impedimetric measurements are
      applied to study the effect of sterilization process on spores of Bacillus
      atrophaeus. This resilient microorganism is commonly used in industry to proof
      the sterilization efficiency. The sensor measurements are accompanied by
      conventional microbiological challenge tests, as well as morphological
      characterizations with scanning electron microscopy (SEM) and transmission
      electron microscopy (TEM). The sensor measurements are correlated with the
      microbiological test routines. In both methods, namely the sensor-based and
      microbiological one, a tailing effect has been observed. The results are
      evaluated and discussed in a three-dimensional calibration plot demonstrating the
      sensor's suitability to enable a rapid process decision in terms of a
      successfully performed sterilization.

PMID- 29328971
TI  - Ultrasensitive electrochemical sensing of Hg2+ based on thymine-Hg2+-thymine
      interaction and signal amplification of alkaline phosphatase catalyzed silver
      deposition.
AB  - We report an ultrasensitive electrochemical sensor for Hg2+ detection, on the
      basis of two Hg2+-specific oligonucleotide probes (a thiolated capture probe and
      a biotinated signal probe), "terminal" signal amplification of alkaline
      phosphatase catalyzed deposition of silver and in situ microliter-droplet anodic
      stripping voltammetry (ASV). The thiolated capture probe is immobilized on an Au
      plated glassy carbon electrode, and the biotinated signal probe is then attached
      to the electrode surface through the thymine-Hg2+-thymine interaction in the
      presence of Hg2+. A streptavidin-alkaline phosphatase (ALP) composite is then
      immobilized on the electrode surface via biotin-streptavidin interaction. The
      immobilized ALP can catalyze the hydrolyzation of ascorbic acid 2-phosphate
      trisodium salt to generate ascorbic acid, which can reduce AgNO3 to form silver
      deposit on the modified electrode. Quantitative analysis of Hg2+ is conducted
      through microliter-droplet ASV of silver after its simultaneous chemical
      dissolution and cathodic preconcentration on the modified electrode. The sensor
      can linearly respond to the common logarithm of Hg2+ concentration from 0.1nM to
      250MUM with a limit of detection of 0.01nM (2 ppt, S/N = 3) and a sensitivity as
      high as 227MUAdec-1.

PMID- 29328972
TI  - Establishment of TUSMi003-A, an induced pluripotent stem cell (iPSC) line from a
      62-year old Chinese Han patient with Alzheimer's disease with ApoE3/4 genetic
      background.
AB  - A 62-year old Chinese Han Alzheimer's disease (AD) female patient with ApoE3/4
      genetic background donated her Peripheral blood mononuclear cells (PBMC). The non
      integrating episomal vector system was used to reprogrammed PBMCs with the human
      OKSM transcription factors. The pluripotency of transgene-free iPSCs was
      confirmed by immunocytochemistry for pluripotency markers and by the ability of
      the iPSCs to differentiate spontaneously into 3 germ layers in vitro. In
      addition, the iPSC line displayed a normal karyotype. Our model might offer a
      good platform to further study the pathological mechanisms, to identify early
      biomarkers, and also for drug testing studies in AD.

PMID- 29328975
TI  - Active elimination of radio frequency interference for improved signal-to-noise
      ratio for in-situ NMR experiments in strong magnetic field gradients.
AB  - Improvement in the signal-to-noise ratio of Nuclear Magnetic Resonance (NMR)
      systems may be achieved either by increasing the signal amplitude or by
      decreasing the noise. The noise has multiple origins - not all of which are
      strictly "noise": incoherent thermal noise originating in the probe and pre
      amplifiers, probe ring down or acoustic noise and coherent externally broadcast
      radio frequency transmissions. The last cannot always be shielded in open access
      experiments. In this paper, we show that pulsed, low radio-frequency data
      communications are a significant source of broadcast interference. We explore two
      signal processing methods of de-noising short T2* NMR experiments corrupted by
      these communications: Linear Predictive Coding (LPC) and the Discrete Wavelet
      Transform (DWT). Results are shown for numerical simulations and experiments
      conducted under controlled conditions with pseudo radio frequency interference.
      We show that both the LPC and DWT methods have merit.

PMID- 29328974
TI  - Novel approach for evaluating pharmaceuticals toxicity using Daphnia model:
      analysis of the mode of cytochrome P450-generated metabolite action after
      acetaminophen exposure.
AB  - Because of its widespread use, the pharmaceutical acetaminophen (APAP) is
      frequently detected in aquatic environments. APAP can have serious physiological
      effects, such as reduced reproduction, low growth rates, and abnormal behavior,
      in aquatic organisms. However, the methods available for evaluation of the
      aquatic toxicity of APAP are of limited usefulness. The present study aimed to
      develop reliable and sensitive markers for evaluation of APAP toxicity using
      Daphnia as a model organism. We focused on N-acetyl-p-benzoquinoneimine (NAPQI)
      production from APAP via cytochrome P450 metabolism because NAPQI causes APAP
      toxicity. Daphnia magna were exposed to APAP (0, 50, or 100 mg/L for 12 h or 24
      h), and the total metabolites were extracted and analyzed for NAPQI. Direct
      detection of NAPQI was difficult because of its high reactivity, and its peak was
      close to that for APAP. Therefore, we tried to identify molecular and biochemical
      indicators associated with NAPQI generation, elimination, and its interactions
      with macromolecules. We identified changes in CYP370A13 gene expression,
      glutathione depletion, inhibition of thioredoxin reductase activity, and
      production of reactive oxygen species as indicators of D. magna exposure to APAP.
      These indicators could be used to develop sensitive and accurate techniques to
      evaluate the environmental toxicity of APAP.

PMID- 29328973
TI  - Feeding inhibition in Corbicula fluminea (O.F. Muller, 1774) as an effect
      criterion to pollutant exposure: Perspectives for ecotoxicity screening and
      refinement of chemical control.
AB  - Bivalves are commonly used in biomonitoring programs to track pollutants. Several
      features, including its filter-feeding abilities, cumulatively argue in favour of
      the use of the Asian clam (Corbicula fluminea) as a biosentinel and an
      ecotoxicological model. Filtration in bivalves is very sensitive to external
      stimuli and its control is dictated by regulation of the opening/closure of the
      valves, which may be used as an avoidance defence against contaminants. Here, we
      investigate the filter-feeding behaviour of the Asian clam as an endpoint for
      assessing exposure to pollutants, driven by two complementary goals: (i) to
      generate relevant and sensitive toxicological information based on the ability of
      C. fluminea to clear an algal suspension, using the invasive species as a
      surrogate for native bivalves; (ii) to gain insight on the potential of exploring
      this integrative response in the refinement of chemical control methods for this
      pest. Clearance rates and proportion of algae removed were measured using a
      simple and reproducible protocol. Despite some variation across individuals and
      size classes, 50-90% of food particles were generally removed within 60-120 min
      by clams larger than 20 mm. Removal of algae was sensitive to an array of model
      contaminants with biocide potential, including fertilizers, pesticides, metals
      and salts: eight out of nine tested substances were detected at the MUg l-1 or mg
      l-1 range and triggered valve closure, decreasing filter-feeding in a
      concentration-dependent manner. For most toxicants, a good agreement between
      mortality (96 h - LC50 within the range 0.4-5500 mg l-1) and feeding (2 h - IC50
      within the range 0.005-2317 mg l-1) was observed, demonstrating that a 120-min
      assay can be used as a protective surrogate of acute toxicity. However, copper
      sulphate was very strongly avoided by the clams (IC50 = 5.3 MUg l-1); on the
      contrary, dichlorvos (an organophosphate insecticide) did not cause feeding
      depression, either by being undetected by the clams' chemosensors and/or by
      interfering with the valve closure mechanism. Such an assay has a large potential
      as a simple screening tool for industry, environmental agencies and managers. The
      ability of dichlorvos to bypass the Asian clam's avoidance strategy puts it in
      the spotlight as a potential agent to be used alone or combined with others in
      eradication programs of this biofouler in closed or semi-closed industrial
      settings.

PMID- 29328976
TI  - Pattern of programmed cell death-ligand 1 expression and CD8-positive T-cell
      infiltration before and after chemoradiotherapy in rectal cancer.
AB  - BACKGROUND: The synergistic effect of combining immune checkpoint inhibitors with
      radiotherapy was reported recently, but there are few studies on programmed cell
      death-ligand 1 (PD-L1) expression in rectal cancer treated by preoperative
      chemoradiotherapy (CRT). The aim of the present study was to investigate the PD
      L1 expression status before and after CRT and its association with
      clinicopathological characteristics and recurrence in rectal cancer. METHODS:
      Immunostainings of PD-L1 and CD8 were performed in 287 patients with rectal
      cancer treated by CRT. PD-L1 expression on the tumour cells (tPD-L1) and on the
      stromal immune cells (iPD-L1) was evaluated before and after CRT. CD8+ cell
      density in tumour area (tCD8+) before CRT and in the stromal area (sCD8+) before
      and after CRT was also evaluated. RESULTS: High tPD-L1 expression was observed in
      only three patients (1.0%). High iPD-L1 expression significantly increased from
      31.7% before CRT to 49.2% after CRT (P < 0.0001). The increase in high iPD-L1
      expression after CRT was only observed in patients with tumour regression grades
      1 and 2. High iPD-L1 expression was associated with high tCD8+ cell density
      before CRT (P < 0.0001) and sCD8+ cell density after CRT (P < 0.0001). High tCD8+
      cell density before CRT was associated with better disease-free survival (DFS) (P
      = 0.0331), but its improved effect on DFS could be observed in patients with high
      iPD-L1 expression (P = 0.0081), not in patients with low iPD-L1 expression (P =
      0.516). CONCLUSION: The present study demonstrated the significant correlations
      between iPD-L1 expression and CD8+ cell density both before and after CRT.

PMID- 29328977
TI  - Skin-lightening practices among female high school students in Ghana.
AB  - OBJECTIVE: The practice of skin lightening (SL) persist despite warnings about
      its harmful health effects. Adolescents are particularly vulnerable and at risk
      of prolonged use of SL products. We explored SL practices among high school
      students in Ghana, West Africa. STUDY DESIGN: Cross-sectional survey. METHODS: We
      used a self-administered questionnaire in a survey on SL practices among randomly
      selected female students in five Senior High Schools in the Brong Ahafo Region of
      Ghana. We determined prevalence and used bivariate and multivariate analysis to
      identify factors associated with the practice. RESULTS: A total of 410 students
      with a mean age of 17.6 years (+/-1.6) participated in the study. While 71.5% of
      students indicated that they had been approached by relatives and friends to use
      SL creams, 65.6% admitted to actually using it. Most (85.5%) students identified
      at least five friends who were using SL products at the time of the survey.
      Between 22.0% and 44.0% of students knew female teachers who practiced SL.
      Students in first year were twice as likely to practice SL compared with students
      in third year (odds ratio [OR] = 1.90, 95% confidence interval [CI] 1.15-3.13).
      Compared with those who had never been approached, students who had been
      approached by relatives and friends to use SL products were likely to be using it
      (OR = 2.24, 95% CI 1.43-3.53). Students who had sisters who used SL products were
      twice as likely to be users themselves (OR = 1.82, 95% CI 1.12-2.95). CONCLUSION:
      The practice of SL among female students in this study is high, and about the
      same as reported among adults in Ghana and other parts of sub-Saharan Africa.
      This suggests that the practice is well entrenched. A ban on the sale of SL
      products to adolescents in Ghana should be considered.

PMID- 29328978
TI  - Sun behaviour on the beach monitored by webcam photos.
AB  - OBJECTIVES: To prevent skin cancer, the general population is recommended to
      limit time in the sun, to wear clothes and to seek shade around noon. This study
      aimed to investigate the number of beachgoers, the duration of sun exposure, and
      clothing worn during the day on a beach in Copenhagen. STUDY DESIGN:
      Observational, descriptive study. METHODS: On 11 beach days in 2014 and 2015,
      beachgoers were counted every hour from 8:00 to 20:00. It was noted if they wore
      clothes or swimwear. To estimate the duration of sun exposure, it was noted how
      long cars were parked by the beach. RESULTS: Of the counted beachgoers 46% were
      present from noon to 15:00. The number of beachgoers peaked at 15:00 on weekend
      days (Saturdays and Sunday) and at 16:00 on working days (Monday to Friday). Both
      on weekend days and working days, the percentage of beachgoers wearing clothes
      was lowest at 13:00 when about 90% wore only swimwear. Cars were parked for 117
      min on average. Around noon, the mean time expanded to 142 min. We assume this to
      reflect the duration of a beach visit. CONCLUSION: The results indicate a weak
      tendency to limit time in the sun and to seek shade when the ultraviolet
      radiation is strongest in the midday sun. Hopefully information about actual sun
      behaviour can be used to adjust campaigns.

PMID- 29328980
TI  - Consequence of intraventricular hemorrhage on neurovascular coupling evoked by
      speech syllables in preterm neonates.
AB  - Intraventricular Hemorrhage (IVH) is the leading cause of neurological and
      cognitive impairment in preterm neonates with an incidence that increases with
      increasing prematurity. In the present study, we tested how preterm neonates with
      IVH react to external stimulation (i.e. speech syllables). We compared their
      neural responses measured by electroencephalography (EEG), and hemodynamic
      responses measured by functional near-infrared spectroscopy (fNIRS), with those
      of healthy preterms. A neural response to syllables was observed in these
      infants, but did not induce a vascular response in contrast with healthy
      neonates. These results clearly demonstrate that the cerebral vascular network in
      IVH preterm neonates was unable to compensate for the increased metabolism
      resulting from neuronal activation in response to external stimulation. Optical
      imaging is thus a sensitive tool to identify altered cerebral hemodynamic in
      critically ill preterms before behavioral changes are manifested or when only
      minor abnormalities on other functional monitoring techniques such as EEG are
      visible. We propose that a multi-modal approach provides unique opportunities for
      early monitoring of cognitive functions and opens up new possibilities for
      clinical care and recommended practices by studying the difficulties of the
      premature brain to adapt to its environment.

PMID- 29328979
TI  - Concurrent validity and interrater reliability of a new smartphone application to
      assess 3D active cervical range of motion in patients with neck pain.
AB  - BACKGROUND: There is a lack of valid, reliable, and feasible instruments for
      measuring planar active cervical range of motion (aCROM) and associated 3D
      coupling motions in patients with neck pain. Smartphones have advanced sensors
      and appear to be suitable for these measurements. OBJECTIVES: To estimate the
      concurrent validity and interrater reliability of a new iPhone application for
      assessing planar aCROM and associated 3D coupling motions in patients with neck
      pain, using an electromagnetic tracking device as a reference test. DESIGN: Cross
      sectional study. METHODS: Two samples of neck pain patients were recruited; 30
      patients for the validity study and 26 patients for the reliability study.
      Validity was estimated using intraclass correlation coefficients (ICCs), and by
      calculating 95% limits of agreement (LoA). To estimate interrater reliability,
      ICCs were calculated. Cervical 3D coupling motions were analyzed by calculating
      the cross-correlation coefficients and ratio between the main motions and coupled
      motions for both instruments. RESULTS: ICCs for concurrent validity and
      interrater reliability ranged from 0.90 to 0.99. The width of the 95% LoA ranged
      from about 5 degrees  for right lateral bending to 11 degrees  for total
      rotation. No significant differences were found between both devices for
      associated coupling motion analysis. CONCLUSIONS: The iPhone application appears
      to be a useful discriminative tool for the measurement of planar aCROM and
      associated coupling motions in patients with neck pain. It fulfills the need for
      a valid, reliable, and feasible instrument in clinical practice and research.
      Therapists and researchers should consider measurement error when interpreting
      scores.

PMID- 29328981
TI  - A simple LC-MS/MS method for determination of deferasirox in human plasma:
      Troubleshooting of interference from ferric ion in method development and its
      application.
AB  - As an orally active iron chelator, deferasirox forms its ion complexes in the
      prepared plasma samples and LC-MS mobile phase where ferric ion exists, and then
      comparing with the nominal concentration level, a lower detected concentration
      level of deferasirox would be obtained after LC-MS analysis, if no proper
      treatment was adopted. Meanwhile, the phenomenon would be observed that multiple
      repeat injections of the same deferasirox plasma sample in the same tube would
      show the lower and lower detected concentration levels of deferasirox, which
      caused by more and more ferric ions from the injection needle dissolved in the
      sample solution as multiple repeated injections. The addition of a proper
      concentration of EDTA in the mobile phase and the sample will competitively
      inhibit deferasirox from complexing with ferric ion, and prevent the decrease of
      deferasirox concentration. In this paper, an LC-MS/MS method was developed and
      validated for the determination of deferasirox in human plasma. To achieve the
      protein precipitation, the analytes were extracted from aliquots of 200 MUL human
      plasma with acetonitrile. Chromatographic separation was performed on an ODS-C18
      column with the mobile phase consisted of methanol and 0.1% formic acid
      containing 0.04 mM ethylenediamine tetraacetate dihydrate (EDTA) (80:20, v/v) at
      a flow rate of 0.5 mL/min. Deferasirox and the internal standard (IS,
      mifepristone) were detected using electrospray ionization in positive ion
      multiple reaction monitoring mode by monitoring the precursor-to-product ion
      transitions m/z 374.2 -> 108.1 for deferasirox and m/z 430.1 -> 372.2 for the IS.
      The method exhibited good linearity over the concentration range of 0.04-40
      MUg/mL for deferasirox. The method was successfully applied to a pharmacokinetic
      study in 10 Chinese healthy volunteers after oral administration of deferasirox.

PMID- 29328982
TI  - Systematic identification of suspected anthelmintic benzimidazole metabolites
      using LC-MS/MS.
AB  - Metabolite reference standards are often not available, which results in a lack
      of MS/MS spectra for library matching. Consequently, the identification of
      suspected metabolites proves to be challenging. The present study aims at
      structurally elucidating the MS/MS fragmentation behavior of selected
      benzimidazole anthelmintics to theoretically predict characteristic product ions
      for rapid and systematic tentative metabolite identification. A set of common
      characteristic product ions was identified from accurate mass MS/MS experiments
      for five parent compounds. It was hypothesized that the mass shift of any
      metabolic transformation at the parent molecule also is observable in the mass
      spectrum of the corresponding metabolite. This was tested and verified with six
      metabolite reference standards and subsequently, formulated as a general
      prediction scheme. The approach was integrated into a rapid MSe QTOF workflow and
      tested in mouse plasma for mebendazole and its metabolites. The presented scheme
      allows the prediction of characteristic product ions for suspected unknown
      metabolites. These can be matched with measured product ions of suspected
      metabolites for tentative identification. The theoretically predicted spectra can
      contribute to the tentative identification of unknown compounds in non-target and
      suspect screening approaches.

PMID- 29328983
TI  - Social and cognitive control skills in long-life occupation activities modulate
      the brain reserve in the behavioural variant of frontotemporal dementia.
AB  - BACKGROUND: Cognitive reserve may delay disease onset and mitigate symptoms
      presentation in neurodegenerative dementias. Although high occupation levels can
      be associated with higher cognitive reserve in the behavioural variant of
      frontotemporal dementia (bvFTD), it was never addressed how specific occupation
      profiles involving social interaction, executive and attention abilities can
      modulate neural reserve in bvFTD. MATERIALS AND METHODS: We retrospectively
      included thirty-seven bvFTD patients with clinical-neuropsychological and FDG-PET
      brain metabolic data. We considered occupation levels according to 1) a 5-point
      scale and 2) the specific cognitive dimensions from the O*Net network database.
      We used the Principal Component Analysis (PCA) with the O*Net variables most
      representative of "worker" and "occupation" socio-cognitive skills to merge the
      best components describing such occupation profiles. We then performed regression
      analyses with brain metabolism using either 5-level occupation scale or the PCA
      specific profiles as independent variables, controlling for education and disease
      severity. RESULTS: According to the brain reserve hypothesis, higher occupation
      levels were associated with a more severe hypometabolism in the dorsolateral
      prefrontal cortex. In addition, among the identified PCA profiles, social skills
      were associated with severe hypometabolism in medial and dorsolateral prefrontal
      regions, and cognitive control in the left fronto-insular cortex. DISCUSSION:
      This study contributes to define the role of specific occupation profiles as
      proxy of cognitive reserve in bvFTD, providing the first evidence for social
      interaction and cognitive control skills in life-occupation activities as
      influencing factors of neural reserve against neurodegeneration in bvFTD. Jobs
      placing high demand on such abilities seem to act as protective factors in bvFTD.

PMID- 29328984
TI  - Does college major matter for women's and men's health in midlife? Examining the
      horizontal dimensions of educational attainment.
AB  - Studies on how education shapes adult health have largely conceptualized
      education as the quantity of schooling attained, coined the "vertical dimension"
      of education. While this dimension is important, heterogeneity within levels of
      education (the "horizontal dimension") may also shape health. Using data from the
      2010-2014 American Community Survey on adults aged 45-64 with a Bachelor's degree
      (N = 667,362), we investigate the association between a key indicator of adult
      health (physical functioning) and an understudied horizontal dimension of
      education (college major). We find that physical functioning in midlife varies
      significantly by college major. For instance, the odds of poor functioning for
      men who majored in Psychology/Social Work were 1.9 (95% CI: 1.7, 2.1) times
      greater than for men who majored in Business. However, all college graduates,
      regardless of major, report better functioning than non-graduates. We also find
      that inequalities in midlife functioning across majors largely reflect
      differences in human capital skills and financial returns in the labor market.
      Taken together our findings suggest that college major is an important component
      of health stratification and should be integrated into the literature on health
      inequalities.

PMID- 29328986
TI  - Post-anaerobic digestion thermal hydrolysis of sewage sludge and food waste:
      Effect on methane yields, dewaterability and solids reduction.
AB  - Post-anaerobic digestion (PAD) treatment technologies have been suggested for
      anaerobic digestion (AD) to improve process efficiency and assure hygenization of
      organic waste. Because AD reduces the amount of organic waste, PAD can be applied
      to a much smaller volume of waste compared to pre-digestion treatment, thereby
      improving efficiency. In this study, dewatered digestate cakes from two different
      AD plants were thermally hydrolyzed and dewatered, and the liquid fraction was
      recirculated to a semi-continuous AD reactor. The thermal hydrolysis was more
      efficient in relation to methane yields and extent of dewaterability for the cake
      from a plant treating waste activated sludge, than the cake from a plant treating
      source separated food waste (SSFW). Temperatures above 165  degrees C yielded the
      best results. Post-treatment improved volumetric methane yields by 7% and the COD
      reduction increased from 68% to 74% in a mesophilic (37  degrees C) semi
      continuous system despite lowering the solid retention time (from 17 to 14 days)
      compared to a conventional system with pre-treatment of feed substrates at 70 
      degrees C. Results from thermogravimetric analysis showed an expected increase in
      maximum TS content of dewatered digestate cake from 34% up to 46% for the SSFW
      digestate cake, and from 17% up to 43% in the sludge digestate cake, after the
      PAD thermal hydrolysis process (PAD-THP). The increased dewatering alone accounts
      for a reduction in wet mass of cake leaving the plant of 60% in the case of
      sludge digestate cake. Additionaly, the increased VS-reduction will contribute to
      further reduce the mass of wet cake.

PMID- 29328985
TI  - Standing on a sliding board affects generation of anticipatory and compensatory
      postural adjustments.
AB  - Postural control is compromised in the presence of body instability. We studied
      anticipatory and compensatory postural adjustments people use to maintain balance
      while standing on an unstable surface and performing voluntary arm movements.
      Nine healthy participants stood on a sliding board (that was either locked and as
      such motionless or unlocked and as such free to move in the anterior-posterior
      direction) and performed fast bilateral arms flexion. Arm acceleration, bilateral
      electromyographic activity (EMG) of the trunk and lower extremity muscles and
      center of pressure (COP) displacements were recorded and analyzed within the
      intervals typical for the anticipatory (APAs) and compensatory (CPAs) postural
      adjustments. Peaks of acceleration of the arm movements were not different
      between the locked and unlocked conditions. Larger EMG integrals were seen in the
      muscles of the lower extremity in both APAs and CPAs when standing on the
      unlocked sliding board. No significant difference was observed in the trunk
      muscles. Larger maximum COP displacement was seen when participants stood on the
      locked board. The results demonstrated that when standing on a free to move
      sliding board and performing bilateral arm flexion, the central nervous system
      (CNS) does not slow down the arm movements; instead it modifies activation of the
      lower extremity muscles. The observed differences in APAs and CPAs between the
      locked and unlocked conditions suggest that the CNS employs similar strategy
      while controlling the focal part of the task and adjusts the activity of muscles
      that are close to the source of instability to control postural task.

PMID- 29328987
TI  - Total mercury content in commercial swordfish (Xiphias gladius) from different
      FAO fishing areas.
AB  - Mercury (Hg) is a global pollutant that affect human and ecosystem health. It is
      transferred through trophic level and bio magnification in the food chain. In
      this study, total Hg was measured in the muscular tissue of samples of swordfish
      (Xiphias gladius) from different FAO fishing areas and imported in Italy between
      2014 and 2017. Total mercury concentrations of muscular tissues were determined
      using cold vapour atomic absorption spectrometry. In order to assess the health
      risk associated with human consumption of this fish, the Hg intake values were
      calculated and compared with those of provisional tolerable daily intake (PTDI)
      (0.57 MUg/kg b.w.) as fixed by the Food and Agriculture Organization/World Health
      Organization (FAO/WHO). The estimated PTDI (provisional tolerable daily intake)
      were lower for adults (0.40 MUg/kg b.w./day) but not for children (0.97 MUg/kg
      b.w./day), and therefore is considered to pose an alert for children with the
      present fish consumption volume.

PMID- 29328988
TI  - Carboxymethyl cellulose stabilized ZnO/biochar nanocomposites: Enhanced
      adsorption and inhibited photocatalytic degradation of methylene blue.
AB  - Biochar(BC)-supported nanoscaled zinc oxide (nZO) was encapsulated either with
      (nZORc/BC) or with no (nZOR/BC) sodium carboxymethyl cellulose (CMC). The X-ray
      diffraction and ultraviolet (UV)-visible-near infrared spectrophotometry revealed
      that nZO of 16, 10, and 20 nm with energy band gaps of 2.79, 3.68 and 2.62 eV
      were synthesized for nZOR/BC, nZORc/BC and nZO/BC, respectively. The Langmuir
      isotherm predicted saturated sorption of methylene blue (MB) was 17.01 g kg-1 for
      nZORc/BC, over 19 times greater than nZOR/BC and nZO/BC. Under UV irradiation,
      10.9, 61.6, 83.1, and 41.6% of MB were degraded for nZORc/BC, nZO/BC, nZOR/BC and
      BC. The scavenging experiment revealed hydroxyl radical dominated CMC
      degradation. Exogenous CMC (2 g L-1) increased MB sorption from 10.6% to 73.1%,
      but decreased MB degradation from 80.7% to 41.1%, relative to nZOR/BC. Thus, CMC
      could increase MB sorption by electrostatic attraction and other possible
      mechanisms. The compromised MB degradation may be ascribed to reduced
      availability of hydroxyl and superoxide radicals to degrade MB, and increased
      band gap energy of ZnO.

PMID- 29328989
TI  - Inhibition of UDP-glucuronosyltransferases (UGTs) by phthalate monoesters.
AB  - Phthalate monoesters are important metabolites of phthalate esters (PAEs) which
      have been extensively utilized in industry. This study aims to investigate the
      inhibition of phthalate monoesters on the activity of various isoforms of UDP
      glucuronosyltransferases (UGTs), trying to elucidate the toxicity mechanism of
      environmental endocrine disruptors from the new perspectives. In vitro
      recombinant UGTs-catalyzed glucuronidation of 4-methylumbelliferone (4-MU) was
      employed to evaluate 8 kinds of phthalate monoesters on 11 sorts of main human
      UGT isoforms. 100 MUM phthalate monoesters exhibited negligible inhibition
      towards the activity of UGT1A1, UGT1A3, UGT1A6, UGT1A8, UGT1A10, UGT2B4, UGT2B7,
      UGT2B15 and UGT2B17. The activity of UGT1A7 was strongly inhibited by
      monoethylhexyl phthalate (MEHP), but slightly inhibited by all the other
      phthalate monoesters. UGT1A9 was broadly inhibited by monobenzyl phthalate
      (MBZP), monocyclohexyl phthalate (MCHP), MEHP, monohexyl phthalate (MHP) and
      monooctyl phthalate (MOP), respectively. MEHP exhibited competitive inhibition
      towards UGT1A7, and MBZP, MCHP, MEHP, MHP and MOP showed competitive inhibition
      towards UGT1A9. The inhibition kinetic parameters (Ki) were calculated to be
      11.25 MUM for MEHP-UGT1A7, and 2.13, 0.09, 1.17, 7.47, 0.16 MUM for MBZP-UGT1A9,
      MCHP-UGT1A9, MEHP-UGT1A9, MHP-UGT1A9, MOP-UGT1A9, respectively. Molecular docking
      indicated that both hydrogen bonds formation and hydrophobic interactions
      significantly contributed to the interaction between phthalate monoesters and UGT
      isoforms. All these information will be beneficial for understanding the adverse
      effects of PAEs.

PMID- 29328991
TI  - Comparison of effects of charge delocalization and pi-electron delocalization on
      the stability of monocyclic compounds.
AB  - Aromaticities and stabilities of ortho, meta, and para isomers of some
      derivatives of benzene, C5H5- and C7H7+ were studied and compared basis on the
      NICS index and their relative energies. For the benzene and C7H7+ derivatives,
      the ortho isomers with less stability were more aromatic. This discrepancy was
      also observed for the molecules with conjugated and non-conjugated pi-electrons.
      However, for the charged conjugated systems, the structures with delocalized
      charge were more stable. Effect of electron withdrawing (EWGs) and electron
      donating groups (EDGs) on the electron delocalization and stability of the
      neutral and charged molecules was investigated. It was observed that the EWDs and
      EDGs change the stability trend of the neutral systems, while in the case of
      charged molecules, the isomers with delocalized charge were more stable
      regardless of the type of substituents. Although both pi-electron delocalization
      and charge delocalization stabilize the aromatic and conjugated systems, effect
      of charge delocalization on the stability is more than that of pi-electron
      delocalization.

PMID- 29328990
TI  - The amyloidogenicity of the influenza virus PB1-derived peptide sheds light on
      its antiviral activity.
AB  - The influenza virus polymerase complex is a promising target for new antiviral
      drug development. It is known that, within the influenza virus polymerase
      complex, the PB1 subunit region from the 1st to the 25th amino acid residues has
      to be is in an alpha-helical conformation for proper interaction with the PA
      subunit. We have previously shown that PB1(6-13) peptide at low concentrations is
      able to interact with the PB1 subunit N-terminal region in a peptide model which
      shows aggregate formation and antiviral activity in cell cultures. In this paper,
      it was shown that PB1(6-13) peptide is prone to form the amyloid-like fibrillar
      aggregates. The peptide homo-oligomerization kinetics were examined, and the
      affinity and characteristic interaction time of PB1(6-13) peptide monomers and
      the influenza virus polymerase complex PB1 subunit N-terminal region were
      evaluated by the SPR and TR-SAXS methods. Based on the data obtained, a
      hypothesis about the PB1(6-13) peptide mechanism of action was proposed: the
      peptide in its monomeric form is capable of altering the conformation of the PB1
      subunit N-terminal region, causing a change from an alpha helix to a beta
      structure. This conformational change disrupts PB1 and PA subunit interaction
      and, by that mechanism, the peptide displays antiviral activity.

PMID- 29328992
TI  - Transcriptome-wide identification and competitive disruption of sacum-binding
      partners in human colorectal cancer.
AB  - Human sacum is regulatory adaptor protein involved in cellular signaling network
      of colorectal cancer. Molecular evidences suggest that the protein is integrated
      into oncogenic signaling network by binding to SH3-containing proteins through
      its proline-rich motifs. In this study, we have performed a transcriptome-wide
      analysis and identification of sacum-binding partners in the genome profile of
      human colorectal cancer. The sacum-binding potency of SH3-containing proteins
      found in colorectal cancer was investigated by using bioinformatics modeling and
      intermolecular binding analysis. With the protocol we were able to predict those
      high-affinity domain binders of the proline-rich peptides of human sacum in a
      high-throughput manner, and to analyze sequence-specific interaction in the
      domain-peptide recognition at molecular level. Consequently, a number of putative
      domain binders with both high affinity and specificity were identified, from
      which the Src SH3 domain was selected as a case study and tested for its binding
      activity towards the sacum peptides. We also designed two peptide variants that
      may have potent capability to competitively disrupt sacum interaction with its
      partners.

PMID- 29328993
TI  - Activity-based classification circumvents affinity prediction problems for
      pyrrolidine carboxamide inhibitors of InhA.
AB  - Developing reliable structure-based activity prediction models for a particular
      ligand series can be challenging if the target is flexible and the affinity range
      of the training compounds is narrow. For a data set of 44 pyrrolidine carboxamide
      inhibitors of the mycobacterial enoyl-ACP-reductase InhA this proved to be case,
      as scoring methods of various origin and complexity did not succeed in providing
      practically useful correlations with experimental inhibition data. In contrast,
      logistic regression models for activity-based classification trained with
      combinations of scoring functions led to good separation of the more active
      inhibitors from the weakest compounds. The approach is suggested as an
      alternative in cases where classical scoring and ranking procedures fail.

PMID- 29328994
TI  - Does high pressure have any effect on the structure of alpha amylase and its
      ability to binding to the oligosaccharides having 3-7 residues? Molecular
      dynamics study.
AB  - Studies have shown that deletion of amino acids from the C-terminus of amylase do
      not alter its amylolytic activity. Although high pressure is used to modify the
      structure and function of this enzyme, the effects of high pressures on the
      structures of the wild-type and truncated amylases have not yet been understood
      at the molecular level. Using molecular dynamic simulations and docking, we
      studied the structures of wild-type and truncated Taka-amylases at high pressures
      (1000-4000 bar). To construct the truncated Taka-amylase, 50 and 100 C-terminal
      residues were removed in two separate steps. Results of simulation showed that,
      although the overall shape partly agglomerates with rise in pressure, high
      pressure fails to modify the structure of the barrel-like region of the beta
      sheet in the wild-type and truncated enzymes. A comparison of contact graphs
      revealed that the changes at the N-terminus were less extensive than those at the
      C-terminus. Further analysis showed that 10 regions of the secondary structures
      changed due to pressure change in wild-type amylase, of which 6 regions were
      associated with the loops and 4 with helix, while the structure of beta-sheets
      remained unchanged. The docking of maltotriose, maltotetraose, maltopentaose,
      maltohexaose, and maltoheptaose with the averaged structures obtained from
      different simulations was conducted to characterize the influence of pressure on
      the activities of the wild-type and truncated enzymes. The results showed that
      maltoheptaose made hydrophobic contacts with residues Tyr238-Asp117-Tyr82-Leu166
      Leu232-Tyr155 and hydrogen contacts with residues Asp233-Gly234-Asp206-Arg204
      His296-Glu230. Similar results were obtained for other malto-oligosaccharides.

PMID- 29328995
TI  - FilTer BaSe: A web accessible chemical database for small compound libraries.
AB  - Finding novel chemical agents for targeting disease associated drug targets often
      requires screening of large number of new chemical libraries. In silico methods
      are generally implemented at initial stages for virtual screening. Filtering of
      such compound libraries on physicochemical and substructure ground is done to
      ensure elimination of compounds with undesired chemical properties. Filtering
      procedure, is redundant, time consuming and requires efficient
      bioinformatics/computer manpower along with high end software involving huge
      capital investment that forms a major obstacle in drug discovery projects in
      academic setup. We present an open source resource, FilTer BaSe- a
      chemoinformatics platform (http://bioinfo.net.in/filterbase/) that host fully
      filtered, ready to use compound libraries with workable size. The resource also
      hosts a database that enables efficient searching the chemical space of around
      348,000 compounds on the basis of physicochemical and substructure properties.
      Ready to use compound libraries and database presented here is expected to aid a
      helping hand for new drug developers and medicinal chemists.

PMID- 29328996
TI  - Acute and sub-acute neurological toxicity in children treated for acute
      lymphoblastic leukemia.
AB  - Eighty percent of children with acute lymphoblastic leukemia (ALL) survive with
      current treatments. Neurotoxicity is an infrequent adverse event. We describe
      clinical presentations of neurological toxicity, phases of treatment when these
      adverse events were more frequent and patients  outcome. From January-1995 to
      December-2015, 1379 ALL cases were admitted. Neurotoxicity was diagnosed in 49
      patients (3.6%) and classified according to neurological syndromes. Medical
      records, laboratory-tests and images were reviewed. The diagnosed syndromes were:
      a) Methotrexate-leukoencephalopathy (MLE) (35.4%); b) Cerebral-venous-sinus
      thrombosis following L-Asparaginase administration (26.5%); c) Vincristine
      induced-vocal-cord paralysis (VVCP) (14.2%); d) Stroke-associated vasospasm
      (14%), after high-dose methotrexate e) Severe polyneuropathy (6.1%); f)
      Methotrexate myelopathy (2%); and g) Pseudotumor-cerebri (2%) associated with
      corticosteroid therapy. Neurotoxicity was diagnosed during induction in 55% of
      cases. We conclude that MLE was the most frequent syndrome. VVCP was observed in
      infants and Down patients. Seizure was the most common symptom and toxicity
      occurred mainly during induction phase.

PMID- 29328997
TI  - Synthesis, biological evaluation and molecular modeling of novel
      thienopyrimidinone and triazolothienopyrimidinone derivatives as dual anti
      inflammatory antimicrobial agents.
AB  - New thienopyrimidinone and triazolothienopyrimidinone derivatives have been
      synthesized. These compounds were subjected to anti-inflammatory and
      antimicrobial activity screening aiming to identify new candidates that have dual
      anti-inflammatory and antimicrobial activities. Compounds 5, 7 and 10a showed
      minimal ulcerogenic effect and high selectivity towards human recombinant COX-2
      over COX-1 enzyme. Their docking outcome correlated with their biological
      activity and assured the high selectivity binding towards COX-2. In addition,
      they could act safely up to 80 mg/kg orally or 40 mg/kg parentrally. The
      antimicrobial screening showed that compound 10a displayed distinctive inhibitory
      effect on the growth of Escherichia coli comparable to that of ampicillin.
      Moreover, compounds 5, 7, 9 and 12a possessed 50% of the inhibitory activity of
      ampicillin against E. coli. Thus, compounds 5, 7 and 10a represent promising dual
      acting anti-inflammatory and antimicrobial agents. This work provides rewarding
      template enriching the chemical space for dual anti-inflammatory anti-microbial
      activities.

PMID- 29328998
TI  - Immunization of mice with egG1Y162-1/2 provides protection against Echinococcus
      granulosus infection in BALB/c mice.
AB  - AIMS: This study is to predict and purify the T-B combined epitopes of egG1Y162
      antigen in Echinococcus granulosus, and to evaluate their immunogenicity in mice.
      METHODS: The bioinformatics software was used to predict the T-B combined
      epitopes of egG1Y162 antigen. Recombinant egG1Y161/2 peptides were constructed,
      expressed and purified. Mice were immunized with egG1Y161/2 peptides. The serum
      and spleen cells were isolated. The isolated spleen cells were stimulated with
      egG1Y161/2 peptides in vitro and the culture supernatant was collected. The
      levels of IgG in serum and levels of IL-4 and IFN-gamma in the culture
      supernatant were measured by ELISA. The weight and number of the fresh hydatid
      cysts were evaluated. The serum ptotoscolicidal activity was measured by the
      complement dependent cytotoxicity assay. RESULTS: Peptides of 6-19aa, 64-82aa,
      106-119aa were predicted as T-B combined epitopes of egG1Y162 antigen. And,
      recombinant protein egG1Y162-1 or egG1Y162-2, which contained T-B combined
      epitope(s) of the 6-19aa, or the 64-82aa and the 106-119aa in egG1Y162 antigen,
      respectively, was successfully expressed and purified. Serum IgG levels of mice
      immunized with egG1Y162-1/2 were significantly increased during the immune
      response to Echinococcus granulosus. The levels of IFN-gamma, IL-4 and the ratio
      of IFN-gamma/IL-4 after egG1Y162-1/2 immunization were significantly higher.
      Weight and number of the fresh hydatid cysts in egG1Y162-1/2 immunized mice was
      significantly decreased. And, the serum protoscolicidal activity after egG1Y162
      1/2 immunization was enhanced. CONCLUSIONS: The egG1Y162-1/2 induces production
      of serum IgG levels and Th1 cell immune response, which enhances the protective
      immunity in Echinococcus granulosus challenged mice and thus may be used as a
      potential vaccine candidate.

PMID- 29328999
TI  - Discovery of novel piperonyl derivatives as diapophytoene desaturase inhibitors
      for the treatment of methicillin-, vancomycin- and linezolid-resistant
      Staphylococcus aureus infections.
AB  - Inhibition of S. aureus diapophytoene desaturase (CrtN) could serve as an
      alternative approach for addressing the tricky antibiotic resistance by blocking
      the biosynthesis of carotenoid pigment which shields the bacterium from host
      oxidant killing. In this study, we designed and synthesized 44 derivatives with
      piperonyl scaffold targeting CrtN and the structure-activity relationships (SARs)
      were examined extensively to bring out the discovery of 21b with potent efficacy
      and better hERG safety profile compared to the first class CrtN inhibitor
      benzocycloalkane derivative 2. Except the excellent pigment inhibitory activity
      against wild-type S. aureus, 21b also showed excellent pigment inhibition against
      four pigmented MRSA strains. In addition, H2O2 killing and human whole blood
      killing assays proved 21b could sensitize S. aureus to be killed under oxidative
      stress conditions. Notably, the murine study in vivo validated the efficacy of
      21b against pigmented S. aureus Newman, vancomycin-intermediate S. aureus Mu50
      and linezolid-resistant S. aureus NRS271.

PMID- 29329000
TI  - Synthesis of C3-Neoglycosides of digoxigenin and their anticancer activities.
AB  - Cardiac glycosides exhibit significant anticancer effects and the glycosyl
      substitution at C3 position of digoxigenin is pivotal for their biological
      activity. In order to study the structure-activity relationship (SAR) of cardiac
      glycosides toward cancers and explore more potent anticancer agents, a series of
      C3-O-neoglycosides and C3-MeON-neoglycosides of digoxigenin were synthesized by
      the Koenigs-Knorr and neoglycosylation method, respectively. In addition,
      digoxigenin bisdigitoxoside and monodigitoxoside were prepared from digoxin by
      sodium periodate (NaIO4) oxidation and 6-aminocaproic acid hydrolysis. The SAR
      analysis revealed that C3-O-neoglycosides of digoxigenin exhibited stronger
      cytotoxicity and induction of Nur77 expression of tumor cells than C3-MeON
      neoglycosides. Also, 3beta-O-glycosides exhibited stronger anticancer effects
      than 3alpha-O-glycosides. Among them, 3beta-O-(beta-l-fucopyranosyl)-digoxigenin
      (3i) showed the highest activity on induction of Nur77 expression and
      translocation from the nucleus to cytoplasm, leading to cancer cell apoptosis.

PMID- 29329001
TI  - Improved antibacterial activity of a marine peptide-N2 against intracellular
      Salmonella typhimurium by conjugating with cell-penetrating peptides
      bLFcin6/Tat11.
AB  - Salmonellae, gram-negative bacteria, are facultative intracellular pathogens that
      cause a number of diseases in animals and humans. The poor penetration ability of
      antimicrobial agents limits their use in the treatment of intracellular bacterial
      infections. In this study, the cell-penetrating peptides (CPPs) bLFcin6 and Tat11
      were separately conjugated to the antimicrobial peptide N2, and the antibacterial
      activity and pharmacodynamics of the CPPs-N2 conjugates were first evaluated
      against Salmonellae typhimurium in vitro and in macrophage cells. The
      cytotoxicity, cellular uptake and mechanism of cellular internalization of the
      CPPs-N2 conjugates were also examined in RAW264.7 cells. Similar to N2, CPPs-N2
      have two reverse beta-sheets and three loops. The minimal inhibitory
      concentration (MIC) of CPPs-N2 was approximately 2 MUM, which was higher than
      that of N2 (0.8 MUM). The dose-time curves and cytotoxicity assay showed that
      both peptide conjugates were more effective than N2 alone at concentrations
      ranging from 0.25 to 1 * MIC, and they exhibited low cytotoxicity (9.78%-13.54%)
      at 100 MUM. After 0.5 h incubation, the cell internalization ratio of B6N2 and
      T11N2 exceeded 28.3% and 93.5%, respectively, which was higher than that of N2.
      The uptake of B6N2 and T11N2 was reduced by low temperature (82.1%-91.7%),
      chlorpromazine (35.7%-75.1%), and amiloride (26.0%-52.1%), indicating that
      macropinocytosis and clathrin-mediated endocytosis may be involved. Approximately
      98.85% and 91.35% of bacteria were killed within 3 h by T11N2 and B6N2,
      respectively, which was higher than the percentage killed by N2 (69.74%).
      Compared with the bactericidal activity of N2 alone, the bactericidal activity of
      T11N2 and B6N2 was increased by 53.7%-99.6% and 85.3-85.8%, respectively. Both
      CPPs-N2 conjugates may be excellent candidates for novel antimicrobial agents to
      treat infectious diseases caused by intracellular pathogens.

PMID- 29329002
TI  - Integration of multi-scale molecular modeling approaches with experiments for the
      in silico guided design and discovery of novel hERG-Neutral antihypertensive
      oxazalone and imidazolone derivatives and analysis of their potential restrictive
      effects on cell proliferation.
AB  - AT1 antagonists is the most recent drug class of molecules against hypertension
      and they mediate their actions through blocking detrimental effects of
      angiotensin II (A-II) when acts on type I (AT1) A-II receptor. The effects of AT1
      antagonists are not limited to cardiovascular diseases. AT1 receptor blockers may
      be used as potential anti-cancer agents - due to the inhibition of cell
      proliferation stimulated by A-II. Therefore, AT1 receptors and the A-II
      biosynthesis mechanisms are targets for the development of new synthetic drugs
      and therapeutic treatment of various cardiovascular and other diseases. In this
      work, multi-scale molecular modeling approaches were performed and it is found
      that oxazolone and imidazolone derivatives reveal similar/better interaction
      energy profiles compared to the FDA approved sartan molecules at the binding site
      of the AT1 receptor. In silico-guided designed hit molecules were then
      synthesized and tested for their binding affinities to human AT1 receptor in
      radioligand binding studies, using [125I-Sar1-Ile8] AngII. Among the compounds
      tested, 19d and 9j molecules bound to receptor in a dose response manner and with
      relatively high affinities. Next, cytotoxicity and wound healing assays were
      performed for these hit molecules. Since hit molecule 19d led to deceleration of
      cell motility in all three cell lines (NIH3T3, A549, and H358) tested in this
      study, this molecule is investigated in further tests. In two cell lines (HUVEC
      and MCF-7) tested, 19d induced G2/M cell cycle arrest in a concentration
      dependent manner. Adherent cells detached from the plates and underwent cell
      death possibly due to apoptosis at 19d concentrations that induced cell cycle
      arrest.

PMID- 29329003
TI  - Modified forest rotation lengths: Long-term effects on landscape-scale habitat
      availability for specialized species.
AB  - We evaluated the long-term implications from modifying rotation lengths in
      production forests for four forest-reliant species with different habitat
      requirements. By combining simulations of forest development with habitat models,
      and accounting both for stand and landscape scale influences, we projected
      habitat availability over 150 years in a large Swedish landscape, using rotation
      lengths which are longer (+22% and +50%) and shorter (-22%) compared to current
      practices. In terms of mean habitat availability through time, species requiring
      older forest were affected positively by extended rotations, and negatively by
      shortened rotations. For example, the mean habitat area for the treecreeper
      Certhia familiaris (a bird preferring forest with larger trees) increased by 31%
      when rotations were increased by 22%, at a 5% cost to net present value (NPV) and
      a 7% decrease in harvested volume. Extending rotation lengths by 50% provided
      more habitat for this species compared to a 22% extension, but at a much higher
      marginal cost. In contrast, the beetle Hadreule elongatula, which is dependent on
      sun-exposed dead wood, benefited from shortened rather than prolonged rotations.
      Due to an uneven distribution of stand-ages within the landscape, the relative
      amounts of habitat provided by different rotation length scenarios for a given
      species were not always consistent through time during the simulation period. If
      implemented as a conservation measure, prolonging rotations will require long
      term strategic planning to avoid future bottlenecks in habitat availability, and
      will need to be accompanied by complementary measures accounting for the
      diversity of habitats necessary for the conservation of forest biodiversity.

PMID- 29329004
TI  - Contemporary enzyme based technologies for bioremediation: A review.
AB  - The persistent disposal of xenobiotic compounds like insecticides, pesticides,
      fertilizers, plastics and other hydrocarbon containing substances is the major
      source of environmental pollution which needs to be eliminated. Many contemporary
      remediation methods such as physical, chemical and biological are currently being
      used, but they are not sufficient to clean the environment. The enzyme based
      bioremediation is an easy, quick, eco-friendly and socially acceptable approach
      used for the bioremediation of these recalcitrant xenobiotic compounds from the
      natural environment. Several microbial enzymes with bioremediation capability
      have been isolated and characterized from different natural sources, but less
      production of such enzymes is a limiting their further exploitation. The genetic
      engineering approach has the potential to get large amount of recombinant
      enzymes. Along with this, enzyme immobilization techniques can boost the half
      life, stability and activity of enzymes at a significant level. Recently,
      nanozymes may offer the potential bioremediation ability towards a broad range of
      pollutants. In the present review, we have described a brief overview of the
      microbial enzymes, different enzymes techniques (genetic engineering and
      immobilization of enzymes) and nanozymes involved in bioremediation of toxic,
      carcinogenic and hazardous environmental pollutants.

PMID- 29329005
TI  - Costs and benefits of biogas recovery from communal anaerobic digesters treating
      domestic wastewater: Evidence from peri-urban Zambia.
AB  - Communal anaerobic digesters (ADs) have been promoted as a waste-to-energy
      strategy that can provide sanitation and clean energy co-benefits. However,
      little empirical evidence is available regarding the performance of such systems
      in field conditions. This study assesses the wastewater treatment efficiency,
      energy production, greenhouse gas (GHG) emissions, and financial costs and
      benefits of communal ADs used for domestic wastewater treatment in Zambia.
      Primary data on the technical performance of 15 ADs were collected over a 6-month
      period and in-person interviews were conducted with heads of 120 households.
      Findings from this study suggest that ADs offer comparable wastewater treatment
      efficiencies and greater GHG emission reduction benefits relative to conventional
      septic tanks (STs), with the greatest benefits in settings with reliable access
      to water, use of low efficiency solid fuels and with sufficient demand for biogas
      in proximity to supply. However, absent a mechanism to monetize additional
      benefits from biogas recovery, ADs in this context will not be a financially
      attractive investment relative to STs. Our financial analysis suggests that,
      under the conditions in this study, a carbon price of US$9 to $28 per tCO2e is
      necessary for positive investment in ADs relative to STs. Findings from this
      study contribute empirical evidence on ADs as a sanitation and clean energy
      strategy, identify conditions under which the greatest benefits are likely to
      accrue and inform international climate efforts on the carbon price required to
      attract investment in emissions reduction projects such as ADs.

PMID- 29329006
TI  - Ongoing unmet needs in treating estrogen receptor-positive/HER2-negative
      metastatic breast cancer.
AB  - Estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2
      negative (HER2-) advanced or metastatic breast cancer (MBC) is the most common
      MBC subtype and currently remains incurable, with a median overall survival of
      24.8 months (95% confidence interval, 21.3-30.3). Common sites of metastases are
      bone, viscera, and brain, causing significant symptoms that negatively affect
      patient functioning, quality of life (QoL), and work productivity. Guidelines
      state that endocrine therapy (ET) is preferable to chemotherapy as first-line
      treatment for patients with ER+ MBC, regardless of limited visceral metastases,
      unless rapid tumor response is required or ET resistance is suspected. Although
      response rates up to 40% have been reported for first-line MBC treatment, the
      majority of initial responders eventually develop ET resistance. Notwithstanding
      the steep decline in efficacy between first and later lines of ET, some patients
      may receive chemotherapy earlier than necessary. Although new treatments have
      been approved for patients with ER+/HER2- advanced or MBC in the past decade,
      neither survival nor QoL appear to have improved significantly. Thus, there
      remain significant unmet needs for this patient population, including improved
      survival, maintaining or improving patient QoL, and emphasizing the importance of
      treatment selection to assist healthcare practitioners managing patient care. In
      this review, we identify current challenges and unmet needs in this patient
      population, review cutting-edge treatments, and provide clinically relevant
      suggestions for treatment selection that can optimize outcomes and patients'
      health-related QoL.

PMID- 29329008
TI  - Selective formation of copper nanoparticles from acid mine drainage using
      nanoscale zerovalent iron particles.
AB  - Nanoscale zerovalent iron (nZVI) has been investigated for the selective
      formation of Cu nanoparticles from acid mine drainage (AMD) taken from a legacy
      mine site in the UK. Batch experiments were conducted containing unbuffered (pH
      2.67 at t = 0) and pH buffered (pH < 3.1) AMD which were exposed to nZVI at 0.1
      2.0 g/L. Results demonstrate that nZVI is selective for Cu, Cd and Al removal
      (>99.9% removal of all metals within 1 h when nZVI >= 1.0 g/L) from unbuffered
      AMD despite the coexistent of numerous other metals in the AMD, namely: Na, Ca,
      Mg, K, Mn and Zn. An acidic pH buffer enabled similarly high Cu removal but
      maximum removal of only <1.5% and <0.5% Cd and Al respectively. HRTEM-EDS
      confirmed the formation of discrete spherical nanoparticles comprised of up to
      68% wt. Cu, with a relatively narrow size distribution (typically 20-100 nm
      diameter). XPS confirmed such nanoparticles as containing Cu degrees , with the
      Cu removal mechanism therefore likely via cementation with Fe degrees . Overall
      the results demonstrate nZVI as effective for the one-pot and selective formation
      of Cu degrees -bearing nanoparticles from acidic wastewater, with the technique
      therefore potentially highly useful for the selective upcycling of dissolved Cu
      in wastewater into high value nanomaterials.

PMID- 29329007
TI  - The relative strength of attitudes versus perceived drinking norms as predictors
      of alcohol use.
AB  - Social cognitive factors such as perceived norms and personal attitudes toward
      alcohol consumption are reliable predictors of alcohol use and related problems.
      The current study aimed to evaluate the relative importance of one's attitude
      toward alcohol use as a unique and important predictor of drinking related
      outcomes when directly compared to perceived descriptive and injunctive norms.
      Participants were mandated students (n=568; 28% female) who violated a campus
      alcohol policy and received a Brief Motivational Intervention. Analyses included
      the use of linear regression for prospective predictions to evaluate the relative
      importance of predictors which included perceived descriptive norms and
      injunctive norms, and attitudes toward moderate and heavy alcohol use. Overall,
      the results indicate that one's attitude toward heavy alcohol use is a stronger
      predictor of drinks per week, binge frequency, as well as alcohol related
      problems when directly compared to norms. Thus, the findings of the current study
      provide a compelling rationale for incorporating attitudes in the development and
      refinement of intervention strategies.

PMID- 29329009
TI  - Well-controlled in-situ growth of 2D WO3 rectangular sheets on reduced graphene
      oxide with strong photocatalytic and antibacterial properties.
AB  - Finding the materials, which help to control the water pollution caused by
      organic and bacterial pollutants is one of the challenging tasks for the
      scientific community. 2D sheets of WO3 and composite of WO3 and reduced graphene
      oxide (rGO) have been synthesized in a well-controlled way using a hydrothermal
      method. The as synthesized 2D sheet of WO3 and rGO-WO3 composite were
      characterized by various techniques. The 2D sheets of WO3 and rGO-WO3 composite
      are efficiently utilized for the photocatalytic degradation of methylene blue
      (MB) and Rhodamine B (RhB) dyes under sunlight. The rGO-WO3 composite reveals
      excellent photocatalytic degradation of RhB dye by degrading it upto 85% under
      sunlight. However, the MB dye was degraded by 32%. The greater degradation of RhB
      dye was explained in terms of the molecular electrostatic potential. We found
      that RhB has a more positive potential compared to MB dye where O2- and OH
      radicals interact more strongly, resulting in a greater degradation of the RhB
      dye. The antibacterial activity of the 2D sheets of WO3 and rGO-WO3composite was
      also investigated on gram positive (B. subtilis) and gram negative (P.
      aeroginosa) microbes for the first time.

PMID- 29329010
TI  - UVA-UVB activation of hydrogen peroxide and persulfate for advanced oxidation
      processes: Efficiency, mechanism and effect of various water constituents.
AB  - In the present work we investigate the activation efficiency of H2O2 and S2O82-
      using UVA and UVB radiation. Bisphenol-A (BPA) is used as model pollutants to
      estimate the oxidative process efficiency in simulated and real sewage treatment
      plant waters. Particular attention is paid to the BPA removal efficiency and to
      the radical mechanism involvement considering the effect of typical inorganic
      water constituents (carbonates and chloride ions) and organic matter. Despite a
      detrimental effect observed when carbonate ions are in solution using both
      hydrogen peroxide and persulafate, the presence of high chloride ions
      concentration was found to improve BPA removal using S2O82- as radical precursor.
      This enhancement, investigated combining chemical kinetic model approach and
      laser flash photolysis experiments, is attributed to the formation of hydroxyl
      radical and chlorine radical species from sulfate radical. Different
      transformation products are identified by means of GC-MS and HPLC-MS analyses.
      Moreover, experiments using sewage treatment plant water (STPW) spiked with BPA
      are performed in order to assess the efficiency of oxidative processes in a
      simulated treatment systems activated using UVA + UVB radiations.

PMID- 29329011
TI  - Removal of ozonation products of pharmaceuticals in laboratory Moving Bed Biofilm
      Reactors (MBBRs).
AB  - The major pathway of pharmaceuticals from urban applications to urban surface
      waters is via wastewater treatment plants. Ozonation is able to remove
      pharmaceuticals from wastewater effluents. However, during that reaction,
      ozonation products are formed. Some ozonation products were found to be
      persistent and have adverse effect on the environment. Moving bed bio reactors
      (MBBRs) were tested for the removal of the ozonation products of macrolide
      antibiotics and diclofenac at two different concentration levels 1 MUg/L and 10
      MUg/L in laboratory reactors. It was found that the MBBRs are capable of
      degrading these compounds without back-transformation into the parent compounds.
      However, reaction rate constants and the degradation kinetics varied for
      different compounds and different concentrations. Depending on compound and
      conditions, the degradation reaction kinetics was found to follow either i) zero
      order ii) first order or iii) lag phase succeeded by first order. The study has
      proven that MBBRs have the potential to be efficient in polishing post ozonation
      treatment.

PMID- 29329012
TI  - Oxidative transformation kinetics and pathways of albendazole from reactions with
      manganese dioxide.
AB  - Albendazole (ABZ) is a benzimidazole-based veterinary anthelmintic used
      extensively in the treatment of intestinal parasites. Due to its high
      hydrophobicity, ABZ tends to accumulate in soils and sediments in the
      environment. This study aims to investigate ABZ's possible degradation by
      manganese oxides. Minor effects from ionic strength and metal cations on ABZ
      degradation were observed. By contrast, decrease of pH greatly enhanced the
      reaction rate. Surface complexation between ABZ and MnO2 was indicated to be the
      dominant control in the reaction kinetics. Suppression by the presence of co
      solvents was negatively proportional to the solvent polarities (suppression from
      high to low: diethyl ether ~ n-butanol > ethanol > methanol > acetonitrile).
      Humic acid was found to cause significant inhibition due to the reductive
      dissolution of MnO2. Four hydrolysis and six oxidative products were identified.
      ABZ and its hydrolysis products containing the propylthio side chain underwent
      the same oxidative transformation to form their corresponding sulfoxide
      compounds. Dehydrogenative coupling reaction between sulfoxide products and
      hydrolysis products could occur to generate dimers. All hydrolysis and oxidative
      products were eluted faster than ABZ in liquid chromatogram, suggesting that the
      spreading out of ABZ will be significantly enhanced if reacting with MnO2.

PMID- 29329013
TI  - Antiobesity effect of Lactobacillus reuteri 263 associated with energy metabolism
      remodeling of white adipose tissue in high-energy-diet-fed rats.
AB  - Obesity is a serious and costly issue to the medical welfare worldwide.
      Probiotics have been suggested as one of the candidates to resolve the obesity
      associated problems, but how they combat obesity is not fully understood. Herein,
      we investigated the effects of Lactobacillus reuteri 263 (L. reuteri 263) on
      antiobesity using four groups of Sprague-Dawley rats (n=10/group), namely, C
      (normal diet with vehicle treatment), HE [high-energy diet (HED) with vehicle
      treatment], 1X (HED with 2.1*109 CFU/kg/day of L. reuteri 263) and 5X (HED with
      1.05*1010 CFU/kg/day of L. reuteri 263), for 8 weeks. L. reuteri 263 improved the
      phenomenon of obesity, serum levels of proinflammatory factors and antioxidant
      enzymes. More importantly, L. reuteri 263 increased oxygen consumption in white
      adipose tissue (WAT). The mRNA expressions of thermogenesis genes uncoupling
      protein-1, uncoupling protein-3, carnitine palmitoyltransferase-1 and cell death
      inducing DFFA-like effector-a were up-regulated in WAT of the 5X group. Moreover,
      L. reuteri 263 might induce browning of WAT due to the higher mRNA levels of
      browning-related genes peroxisome proliferator-activated receptor-gamma, PR
      domain containing-16, Ppargamma coactivator-1alpha, bone morphogenetic protein-7
      and fibroblast growth factor-21 in the 1X and 5X groups compared to the HE group.
      Finally, L. reuteri 263 altered the expressions of genes involved in glucose and
      lipid metabolisms in WAT, including increasing the levels of glucose transporter
      type 4 and carbohydrate-responsive element-binding protein and decreasing the
      expression of Acetyl-CoA carboxylase-1. The results suggest that L. reuteri 263
      may treat obesity through energy metabolism remodeling of WAT in the high-energy
      diet-induced obese rats.

PMID- 29329014
TI  - Nanoadsorbents based on conducting polymer nanocomposites with main focus on
      polyaniline and its derivatives for removal of heavy metal ions/dyes: A review.
AB  - Water contamination by toxic heavy metal ions and dyes remains a serious public
      health problem for humans, so attention on specific methods and technologies to
      remove heavy metal ions and dyes from wastewaters/aqueous solutions are desired.
      Numerous adsorbents have been reported for the removal of heavy metal ions/dyes
      from wastewaters/aqueous solutions. Polyaniline (PANI) and its derivatives, as
      conducting polymers, are good adsorbents to remove various kinds of heavy metal
      ions and dyes from wastewaters/aqueous solutions. The nanoadsorbents based on
      PANI and its derivatives have received much consideration, and are extensively
      reported in literature. This review focuses on the PANI and its derivatives based
      on nanoadsorbents for water purification. Various types of these nanoadsorbents
      used for the removal of heavy metal ions/dyes from wastewaters/aqueous solutions
      are also briefly compared in this review.

PMID- 29329015
TI  - Modelling of road traffic fatalities in India.
AB  - Passenger modes in India include walking, cycling, buses, trains, intermediate
      public transport modes (IPT) such as three-wheeled auto rickshaws or tuk-tuks,
      motorised two-wheelers (2W) as well as cars. However, epidemiological studies of
      traffic crashes in India have been limited in their approach to account for the
      exposure of these road users. In 2011, for the first time, census in India
      reported travel distance and mode of travel for workers. A Poisson-lognormal
      mixture regression model is developed at the state level to explore the
      relationship of road deaths of all the road users with commute travel distance by
      different on-road modes. The model controlled for diesel consumption (proxy for
      freight traffic), length of national highways, proportion of population in urban
      areas, and built-up population density. The results show that walking, cycling
      and, interestingly, IPT are associated with lower risk of road deaths, while 2W,
      car and bus are associated with higher risk. Promotion of IPT has twofold
      benefits of increasing safety as well as providing a sustainable mode of
      transport. The mode shift scenarios show that, for similar mode shift across the
      states, the resulting trends in road deaths are highly dependent on the baseline
      mode shares. The most worrying trend is the steep growth of death burden
      resulting from mode shift of walking and cycling to 2W. While the paper
      illustrates a limited set of mode shift scenarios involving two modes at a time,
      the model can be applied to assess safety impacts resulting from a more complex
      set of scenarios.

PMID- 29329016
TI  - Non-linear effects of the built environment on automobile-involved pedestrian
      crash frequency: A machine learning approach.
AB  - Although a growing body of literature focuses on the relationship between the
      built environment and pedestrian crashes, limited evidence is provided about the
      relative importance of many built environment attributes by accounting for their
      mutual interaction effects and their non-linear effects on automobile-involved
      pedestrian crashes. This study adopts the approach of Multiple Additive Poisson
      Regression Trees (MAPRT) to fill such gaps using pedestrian collision data
      collected from Seattle, Washington. Traffic analysis zones are chosen as the
      analytical unit. The effects of various factors on pedestrian crash frequency
      investigated include characteristics the of road network, street elements, land
      use patterns, and traffic demand. Density and the degree of mixed land use have
      major effects on pedestrian crash frequency, accounting for approximately 66% of
      the effects in total. More importantly, some factors show clear non-linear
      relationships with pedestrian crash frequency, challenging the linearity
      assumption commonly used in existing studies which employ statistical models.
      With various accurately identified non-linear relationships between the built
      environment and pedestrian crashes, this study suggests local agencies to adopt
      geo-spatial differentiated policies to establish a safe walking environment.
      These findings, especially the effective ranges of the built environment, provide
      evidence to support for transport and land use planning, policy recommendations,
      and road safety programs.

PMID- 29329017
TI  - Amiodarone, a multi-channel blocker, enhances anticonvulsive effect of
      carbamazepine in the mouse maximal electroshock model.
AB  - Cardiac arrhythmia may occur in the course of epilepsy. Simultaneous therapy of
      the two diseases might be complicated by drug interactions since antiarrhythmic
      and antiepileptic agents share some molecular targets. The aim of this study was
      to evaluate the influence of amiodarone, an antiarrhythmic drug working as a
      multi-channel blocker, on the protective activity of four classical antiepileptic
      drugs in the maximal electroshock test in mice. Amiodarone at doses up to 75
      mg/kg did not affect the electroconvulsive threshold in mice. Acute amiodarone at
      the dose of 75 mg/kg significantly potentiated the anticonvulsive effect of
      carbamazepine, but not that of valproate, phenytoin or phenobarbital in the
      maximal electroshock-induced seizures in mice. The antiarrhythmic agent and its
      combinations with antiepileptic drugs did not impair motor performance or long
      term memory in mice, except for the combination of amiodarone and phenobarbital.
      Brain concentrations of antiepileptic drugs were not changed. Despite favourable
      impact of amiodarone on the anticonvulsive action of carbamazepine in the maximal
      electroshock, co-administration of the two drugs should be carefully monitored in
      clinical conditions. Further studies are necessary to evaluate effects of chronic
      treatment with amiodarone on seizure activity and the action of antiepileptic
      drugs.

PMID- 29329019
TI  - Salidroside influences the cellular cross-talk of human fetal lung diploid
      fibroblasts: A proteomic approach.
AB  - Senescence is a complex multiple factor proces, which is still poorly understood.
      The purpose of this study was to find the proteome of cultured human fetal lung
      diploid fibroblasts (2BS) of different population doubling (PD), as well as the
      altered proteome induced by salidroside (SAL) in 2BS cells. Proteins were
      identified by two-dimensional electrophoresis (2-DE) combining matrix-assisted
      laser desorption/ionization-time and flight mass spectrometry (MAL DI-TOF/MS). As
      a result, we found 16 proteins with two-fold variations in senescent cells or
      after SAL treatment, some being reduced such as reticulocalbin-1, heat shock
      protein beta-6, elongation factor 1-delta, F-actin-capping protein subunit alpha
      1, and chloride intracellular channel 1. In contrast, 40S ribosomal protein SA,
      proteasome subunit alpha type-5, and zinc finger BED domain-containing protein 5
      increased with cell age. Furthermore, heat shock protein beta-6, Zinc finger BED
      domain-containing protein 5 was increased in PD30 cells after 10 MUM SAL
      treatment, whereas, elongation factor 1-delta, 6-phosphogluconolactonase,
      Nucleoside diphosphate kinase A, F-actin-capping protein subunit alpha-1,
      Probable ATP-dependent RNA helicase DDX41, Chloride intracellular channel 1, and
      Peroxiredoxin-6 were increased in PD50 cells after 10 MUM SAL treatment. Some of
      these proteins were involved in the protein synthetic and degradative pathways,
      which emphasizes the metabolic disorder or functional impairment of cell
      senescence. Moreover, these proteins could be candidate biomarkers for evaluating
      the SAL anti-senescence effect.

PMID- 29329018
TI  - Corrosion effect of Bacillus cereus on X80 pipeline steel in a Beijing soil
      environment.
AB  - The corrosion of X80 pipeline steel in the presence of Bacillus cereus (B.
      cereus) was studied through electrochemical and surface analyses and live/dead
      staining. Scanning electron microscopy and live/dead straining results showed
      that a number of B. cereus adhered to the X80 steel. Electrochemical impedance
      spectroscopy showed that B. cereus could accelerate the corrosion of X80 steel.
      In addition, surface morphology observations indicated that B. cereus could
      accelerate pitting corrosion in X80 steel. The depth of the largest pits due to
      B. cereus was approximately 11.23MUm. Many pits were found on the U-shaped bents
      and cracks formed under stress after 60days of immersion in the presence of B.
      cereus. These indicate that pitting corrosion can be accelerated by B. cereus. X
      ray photoelectron spectroscopy results revealed that NH4+ existed on the surface
      of X80 steel. B. cereus is a type of nitrate-reducing bacteria and hence the
      corrosion mechanism of B. cereus may involve nitrate reduction on the X80 steel.

PMID- 29329020
TI  - A novel mouse model of atopic dermatitis that is T helper 2 (Th2)-polarized by an
      epicutaneous allergen.
AB  - The pathogenesis of atopic dermatitis (AD) involves T helper 2 (Th2) cells, and
      effective therapies remain elusive due to the paucity of animal models. We aimed
      to develop a mouse model of an immune system aberration caused by allergen.
      Experiments were conducted in two phases. In experiment 1, BALB/c mice were
      sensitized with one of four chemical allergens - toluene diisocyanate (TDI),
      hexamethylene diisocyanate (HDI), trimellitic anhydride (TMA), or 2,4
      dinitrochlorobenzene (DNCB) - for 3 weeks. Based on results of experiment 1,
      immunological features were compared between TMA-sensitized BALB/c mice and
      NC/Nga mice, after exposure to mite extracts, harmful chemicals and detergents in
      experiment 2. Sensitization by allergen caused a large number of pathological
      changes in the skin, and an increase in mast cell number. TMA-sensitized BALB/c
      mice models showed higher sensitivity to an environmental allergen than NC/Nga
      mice did. Overall, the initial sensitization with TMA leads to disturbances in
      Th2-mediated immunity.

PMID- 29329021
TI  - Genotoxicity analysis of five particle matter toxicants from cigarette smoke
      based on gammaH2AX assay combined with Hill/Two-component model.
AB  - To investigate the genotoxic characteristics of typical toxicants in particle
      phase of cigarette smoke, including B[a]P, nicotine, tar, NNN and NNK. The in
      vitro gammaH2AX assay was used to detect the DNA double-strand breaks (DSBs) in
      A549 cells using high content screening (HCS). The results showed all toxicants
      had a dose/time-dependent effects on induction of gammaH2AX except for NNN and
      NNK. Based on dose-response of gammaH2AX and Hill model, the ability to induce
      DSBs was evaluated: NNN-acetate > B[a]P > NNK-acetate > tar > nicotine. Based on
      time-course of gammaH2AX and two-component model, the complex DNA damage was the
      main subtypes of DNA damage induced by these toxicants. Overall, all toxicants
      were genotoxic in A549 cells in a dose- or time- dependent manner except for NNN
      and NNK based on the gammaH2AX HCS assay. NNN-acetate had more potential to
      induce DSBs, which was followed by B[a]P, NNK-acetate, tar and nicotine.

PMID- 29329022
TI  - Impact of non-anticoagulant therapy on patients with sepsis-induced disseminated
      intravascular coagulation: A multicenter, case-control study.
AB  - INTRODUCTION: Anticoagulant therapy for patients with sepsis is not recommended
      in the latest Surviving Sepsis Campaign guidelines, and non-anticoagulant therapy
      is the global standard treatment approach at present. We aimed at elucidating the
      effect of non-anticoagulant therapy on patients with sepsis-induced disseminated
      intravascular coagulation (DIC), as evidence on this topic has remained
      inconclusive. MATERIALS AND METHODS: Data from 3195 consecutive adult patients
      admitted to 42 intensive care units for the treatment of severe sepsis were
      retrospectively analyzed via propensity score analyses with and without multiple
      imputation. The primary outcome was in-hospital all-cause mortality. RESULTS:
      Among 1784 patients with sepsis-induced DIC, 745 (41.8%) were not treated with
      anticoagulants. The inverse probability of treatment-weighted (with and without
      multiple imputation) and quintile-stratified propensity score analyses (without
      multiple imputation) indicated a significant association between non
      anticoagulant therapy and higher in-hospital all-cause mortality (odds ratio [95%
      confidence interval]: 1.59 [1.19-2.12], 1.32 [1.02-1.81], and 1.32 [1.03-1.69],
      respectively). However, quintile-stratified propensity score analyses with
      multiple imputation and propensity score matching analysis with and without
      multiple imputation did not show this association. Survival duration was not
      significantly different between patients in the propensity score-matched non
      anticoagulant therapy group and those in the anticoagulant therapy group (Cox
      regression analysis with and without multiple imputation: hazard ratio [95%
      confidence interval]: 1.26 [1.00-1.60] and 1.22 [0.93-1.59], respectively).
      CONCLUSIONS: It remains controversial if non-anticoagulant therapy is harmful,
      equivalent, or beneficial compared with anticoagulant therapy in the treatment of
      patients with sepsis-induced DIC.

PMID- 29329023
TI  - Women's experiences with using a smartphone app (the Pregnant+ app) to manage
      gestational diabetes mellitus in a randomised controlled trial.
AB  - OBJECTIVE: The purpose of this study was to explore the experiences of women with
      gestational diabetes mellitus (GDM) with controlling their blood glucose values
      and receiving health and nutrition information using a smartphone app (the
      Pregnant+ app). DESIGN AND PARTICIPANTS: The study utilised the interpretative
      phenomenological analysis method. Semi-structured interviews were conducted with
      17 participants among those participating to the randomised controlled trial.
      RESULTS: The women experienced sorrow and disappointment when they were diagnosed
      with GDM, but they all went through a process of learning to self-manage their
      condition that was strongly motivated by theirdesire to care for their unborn
      babies. The women found that the app increased their confidence in their self
      management of GDM and their motivation for behavioural change. For some women,
      the app contributed to feelings offrustration or obsession. In addition, some
      technological problems and a lack of support from health-care professionals
      limited several women from using the app. KEY CONCLUSIONS AND IMPLICATIONS FOR
      PRACTISE: The findings suggest that asmartphone app may have potential for
      supporting women with GDM, particularly in their blood glucose management.
      However, it also highlights some of the potential challenges of using mHealth
      technologies. The findings indicate that a closer collaboration between health
      care professionals and patients is of great importance in the implementation of
      apps for women with GDM.

PMID- 29329024
TI  - 'TeamUP': An approach to developing teamwork skills in undergraduate midwifery
      students.
AB  - OBJECTIVE: to develop an effective model to enable educators to teach, develop
      and assess the development of midwifery students' teamwork skills DESIGN: an
      action research project involving participant interviews and academic feedback.
      SETTING: a regional university PARTICIPANTS: midwifery students (n = 21) and new
      graduate midwives (n = 20) INTERVENTIONS: a whole of course program using a
      rubric, with five teamwork domains and behavioural descriptors, to provide a
      framework for teaching and assessment. Students self and peer assess. Lectures,
      tutorials and eight different groupwork assignments of increasing difficulty,
      spread over the three years of the undergraduate degree are incorporated into the
      TeamUP model. FINDINGS: the assignments provide students with the opportunity to
      practice and develop their teamwork skills in a safe, supported environment. KEY
      CONCLUSIONS: the social, emotional and practical behaviours required for
      effective teamwork can be taught and developed in undergraduate health students.
      IMPLICATIONS FOR PRACTICE: students require a clear overview of the TeamUP model
      at the beginning of the degree. They need to be informed of the skills and
      behaviours that the TeamUP model is designed to help develop and why they are
      important. The success of the model depends upon the educator's commitment to
      supporting students to learn teamwork skills.

PMID- 29329025
TI  - The Midwifery Services Framework: The process of implementation.
AB  - In 2015, the International Confederation of Midwives launched the Midwifery
      Services Framework: a new evidence-based tool to guide countries through the
      process of improving their sexual, reproductive, maternal and newborn health
      services through strengthening and developing the midwifery workforce. The
      Midwifery Services Framework is aligned with key global architecture for sexual,
      reproductive, maternal and newborn health and human resources for health, and
      with the recommendations of the 2014 Lancet Series on Midwifery. This second in a
      series of three papers describes the process of implementing the Midwifery
      Services Framework: the preparatory work, what happens at each stage of
      implementation and who should be involved at each stage. It gives an idea of the
      scale of the task, and the resources that will be required to implement the
      Midwifery Services Framework in a given country context. The paper will be of
      interest to health policy-makers, development partners and professional
      associations in countries considering different approaches to strengthening their
      sexual, reproductive, maternal and newborn health services, and it will help them
      to decide whether and when either full or partial/staged implementation of the
      Midwifery Services Framework will be an appropriate initiative to address
      identified deficits in their specific context, given the current and projected
      availability of resources.

PMID- 29329026
TI  - The interaction of pyridoxal isonicotinoyl hydrazone (PIH) and salicylaldehyde
      isonicotinoyl hydrazone (SIH) with iron.
AB  - The interaction of pyridoxal isonicotinoyl hydrazone (PIH) and salicylaldehyde
      isonicotinoyl hydrazone (SIH), two important biologically active chelators, with
      iron has been investigated by spectrophotometric methods. High iron(III) affinity
      constants were determined for PIH, logbeta2=37.0 and SIH, logbeta2=37.6. The
      associated redox potentials of the iron complexes were determined using cyclic
      voltammetry at pH7.4 as +130mV (vs normal hydrogen electrode, NHE) for PIH and
      +136mV(vs NHE) for SIH. These redox potentials are much higher than those
      corresponding to iron chelators in clinical use, namely deferiprone, -620mV;
      desferasirox, -600mV and desferrioxamine, -468mV. Although the positive redox
      potentials of SIH and PIH are similar to that of EDTA, namely +120mV, the iron
      complexes of these two hydrazone chelators, unlike the iron complex of EDTA, do
      not redox cycle in the presence of vitamin C. These properties render PIH and SIH
      as excellent scavengers of iron, under biological conditions. Both SIH and PIH
      scavenge mononuclear iron(II) and iron(III) rapidly. These fast kinetic
      properties of the hydrazone-based chelators provide a ready explanation for the
      adoption of SIH in fluorescence-based methods for the quantification of cytosolic
      iron(II).

PMID- 29329027
TI  - Cytotoxic and anticancer properties of new ruthenium polypyridyl complexes with
      different lipophilicities.
AB  - Three ruthenium complexes containing a bidentate piq ligand, [(piq)Ru(bpy)2]2+
      (1), [(piq)Ru(phen)2]2+ (2), and [(piq)Ru(DIP)2]2+ (3) (piq =
      phenylisoquinolinate, bpy = 2,2'-bipyridine, phen = 1,10-phenanthroline, DIP =
      4,7-diphenyl-1,10-phenanthroline), were prepared. The DNA binding properties of
      complexes 1-3 to double-stranded DNA were studied. The binding of 1-3 to calf
      thymus DNA (ct-DNA) yielded lower emission intensities than those observed with
      the corresponding Ru complexes alone. To explore potential interactions of
      complexes 1-3 with lipid-rich organs in live cells, the emission properties of
      the Ru probes were studied with liposomes. The emission intensities of complexes
      1-3 were enhanced to similar extents upon interaction with liposomes. The
      cytotoxic activities of the complexes against MDA-MB-231 and HUVECs were
      evaluated in vitro. The effects of complexes 1-3 on the survival of MDA-MB-231
      cells were examined and compared with that of cis-platin. Complexes 2 and 3 were
      more cytotoxic to cancer cells than cis-platin. Complexes 1-3 showed cellular
      uptakes of 1.1, 10.6, and 76.6%, respectively, indicating that the greatest
      amount of complex 3 entered the cancer cells. Inhibition of cell migration by
      complexes 1-3 was also evaluated by the wound healing assay.

PMID- 29329028
TI  - Equine allogeneic chondrogenic induced mesenchymal stem cells: A GCP target
      animal safety and biodistribution study.
AB  - The safety of the intra-articular use of mesenchymal stem cells (MSCs) is
      scarcely reported. Therefore, the goal of this study was to investigate the
      safety of a single intra-articular injection with allogeneic chondrogenic induced
      MSCs combined with equine plasma (=the investigational product: IVP) compared to
      a saline (0.9% NaCl) placebo control (=control product: CP). Sixteen healthy
      experimental horses were randomly assigned to receive a single intra-articular
      injection with either the IVP (n=8) or the CP (n=8) in the left
      metacarpophalangeal joint. All horses underwent a daily clinical assessment
      throughout the entire study period of 42days to assess adverse events.
      Additionally, a local joint assessment and a lameness examination were performed
      daily during the first two weeks, and weekly the following 4weeks. Blood samples
      were taken weekly for hematological and biochemical analysis. At the end of the
      study period, horses of the IVP group were euthanized for a thorough necropsy and
      to check for biodistribution. Tissue samples of the injected joint were collected
      for histological examination. In both CP and IVP treated horses a mild transient
      subjective increase in periarticular temperature and lameness was noted after the
      intra-articular injection with no significant differences between the treatment
      groups. No distribution of the cells was found using immunohistochemistry and no
      ectopic tissue formation or signs of inflammation were found on histology. A
      single intra-articular injection of allogeneic chondrogenic induced MSCs combined
      with allogeneic plasma in horses had the same clinical side effects as an intra
      articular injection with saline solution.

PMID- 29329029
TI  - Corrigendum to "Pharmacological profile of dexketoprofen in orofacial pain"
      [Pharmacol. Rep. 68 (6) (2016) 1111-1114].

PMID- 29329030
TI  - pDok2, caspase 3 dependent glioma cell growth arrest by nitidine chloride.
AB  - BACKGROUND: Nitidine chloride (NC) is known to exert anticancer and anti
      metastatic effects on a variety of tumors. Recently, NC has also been shown to
      inhibit PIK3/AKT/mTOR axis in U87 human glioma cells. METHODS: The study shows NC
      employing pDok2, caspase 3 dependent cell death in C6 rat glioma and U87 human
      malignant glioblastoma cells. The effect of NC on glioblastoma cell lines was
      accessed by MTT, clonogenic and wound healing assays. Cell cycle analysis was
      performed by FACS. Moreover, the effect of NC on downstream target proteins, such
      as caspase3, pDok2, PARP, and Gsk3 beta, were measured by western blotting.
      RESULTS: Overexpressed pDok2 protein has recently been reported as a prognostic
      marker with poor outcomes for human glioblastoma multiformae. We found that NC
      inhibits pDok2 in U87 cells in a concentration-dependent way. We further showed
      that cleaved PARP and cleaved caspase 3 protein expressions were increased in C6
      cells treated with NC in a dose-dependent way. NC effectively attenuated C6 cells
      growth and colony formation at 8MUM (micromoles) concentration. Cell cycle arrest
      in G2/M phase was further confirmed by flow cytometry. NC also exhibited its
      inhibitory effect on Gsk3 beta, which has been proven to be altered in glioma
      biology. CONCLUSIONS: Collectively, we predicted that NC could be employed as a
      potential anti-glioma mediator that needs attention to explore the mechanisms of
      its activity.

PMID- 29329031
TI  - Development of a new ex vivo model for evaluation of endoscopic submucosal
      injection materials performance.
AB  - BACKGROUND AND AIMS: Development of high-performance submucosal injection
      materials (SIMs) contribute to the advancement of endoscopic therapy for early
      stage gastrointestinal neoplasms. This study aimed to develop a new ex vivo model
      that mimics the human gastrointestinal tract to evaluate the performance (the
      height and duration of the submucosal elevation) of various SIMs in detail.
      METHODS: A new ex vivo model that applies a constant tension to the tested
      specimen (the porcine gastric specimen) was developed. SIMs were injected into
      the submucosa at the center or edge of the tested specimen, and submucosal
      elevation heights (SEHs) were measured over time. RESULTS: The average value and
      standard deviation of SEH determined using the conventional model (the tested
      specimen was fixed with pins) were higher than those obtained using the new
      model, which showed that the new model could precisely measure the SEH of a given
      SIM. In addition, the performance (SEH) of SIMs decreased with increasing tension
      applied to the specimen, suggesting that the performance of SIMs deteriorates
      with the over-expansion of the gastrointestinal tract. The submucosal elevation
      formed at the specimen edge disappeared faster than that formed at the specimen's
      center. CONCLUSIONS: The proposed new ex vivo model allows accurate SEH
      measurement under uniform conditions and detailed comparison of the performances
      of various types of SIMs and can contribute to the development of high
      performance materials.

PMID- 29329032
TI  - Targeting expression of adenosine receptors during hypoxia induced angiogenesis -
      A study using zebrafish model.
AB  - Hypoxia is known to be a major player during pathological angiogenesis and
      adenosine as a negative feedback signaling to maintain oxygen delivery in
      pathological ischemic condition. We mimicked hypoxic condition and studied
      angiogenesis by inducing adenosine receptors using forskolin, a plant compound
      and NECA analogue of adenosine using zebrafish model. Vascular endothelial growth
      factor (VEGF) is known to play a key role during pathological angiogenesis and
      regulated by the factors HIF1a under hypoxic condition and recently Notch is
      proposed to play a negative feedback loop mechanism along with VEGF signaling but
      the role of adenosine receptor during the process is not known. We evaluated the
      mRNA expression of adenosine receptors (A1, A2a.1, A2a.2, A2b), HIF1a, VEGF A,
      VEGF R2, NRP1a, NOTCH 1a and DLL4 and the phenotypic variations of zebrafish
      embryos when treated with DAPT, gamma-secretase inhibitor of Notch in addition to
      treating the embryos with SU5416, a VEGF receptor inhibitor. Upregulation of
      adenosine receptors (A1, A2a.1, A2a.2, A2b), HIF1a, VEGF A, VEGF R2, NRP1a,
      NOTCH1a and DLL4 was observed embryos were when treated with forskolin and NECA
      could possibly mimic hypoxic condition. Hatching and heart rate also increased
      with NECA and forskolin. SU5416 showed decreases in blood vessel formation and
      decreased adenosine receptors, VEGF, VEGFR2, HIF1a and NRP1a expression and DAPT,
      exhibited decreases in blood vessels and decreased NRP1a, NOTCH1a, DLL4
      expression. These embryos developed with poor vasculature, tail bending, abnormal
      phenotypes and developmental delay. Forskolin treated with inhibitors showed
      increased blood vessel formation, normal phenotype, development and adenosine
      receptors (A1, A2a.1, A2a.2, A2b), HIF1a, VEGF A, VEGF R2, NRP1a, NOTCH 1a and
      DLL4 gene expression suggesting that adenosine mediated Notch and VEGF could play
      an important role during development and angiogenesis. Targeting VEGF and Notch
      signaling with adenosine receptors inhibitors which might have a therapeutic
      significance during hypoxia and abnormal angiogenesis.

PMID- 29329033
TI  - Onjisaponin B prevents cognitive impairment in a rat model of D-galactose-induced
      aging.
AB  - In this study, we investigated the potential effect of onjisaponin B (OB) on
      aging rats induced by D-gal (D-galactose). Sub-acute aging model was established
      in rats by the subcutaneous injection of D-gal (120 mg/kg) for 42 days,
      accompanied with OB (10, 20 mg/kg, p.o.) or normal saline intervention for 28
      days since the 14th day after the beginning of D-gal stimulation. Morris water
      maze test and step-down passive avoidance test were conducted to evaluate the
      cognitive function of the rats. The superoxidase dismutase (SOD), malondialdehyde
      (MDA), glutathione (GSH) and glutathione peroxidase (GSH-px) contents in
      hippocampus were measured by according kits, respectively. And the hippocampus
      levels of inflammatory mediators including tumor necrosis factor-alpha (TNF
      alpha), interleukin-6 (IL-6) and interleukin-1beta (IL-1beta) were assayed by
      enzyme-linked immunosorbent assay (ELISA). Furthermore, the expressions of SOD1,
      MDA5, GSH, GSH-px, NF-kB pathway were present by western blot. It revealed that
      administration of OB was able to significantly attenuate the D-gal-induced
      changes in the hippocampus, ranging from cognitive capacity, oxidative stress to
      inflammation response. In a nutshell, our data provided evidence that OB could
      contribute to the restoration of cognitive ability by improving the antioxidant
      and anti-inflammatory capacity in D-gal induced aging rats.

PMID- 29329034
TI  - Long non-coding RNA CCAT2 promotes cholangiocarcinoma cells migration and
      invasion by induction of epithelial-to-mesenchymal transition.
AB  - Cholangiocarcinoma (CCA) is one of the most aggressive malignancies in humans.
      Emerging evidence has indicated that abnormally expressed long non-coding RNAs
      (lncRNAs) could conduce to tumorigenesis and progression. Specifically, colon
      cancer-associated transcript 2 (CCAT2) has been reported to be overexpressed in
      several carcinomas. However, its clinical significance and functional roles in
      CCA is still unknown. qRT-PCR experiments were conducted to assess the CCAT2
      expression in CCA tissue samples and cell lines. In addition, the link between
      CCAT2 expression and clinicopathological characteristics was analyzed. The
      potential effects of CCAT2 in CCA cells was evaluated in vitro including cell
      proliferation, colony-forming ability, apoptosis, migration, invasion and
      epithelial-to-mesenchymal transition (EMT). As a result, CCAT2 was aberrantly
      overexpressed in CCA tissue samples and cells, and this upregulation was
      correlated with tumor size, lymph node invasion, TNM stage and postoperative
      recurrence in CCA patients. Overexpression of CCAT2 could serve as an independent
      prognostic indicator for CCA. Additionally, overexpression of CCAT2 was a dismal
      prognostic indicator for patients with CCA. Furthermore, CCAT2 silencing caused
      tumor suppressive effects via reducing cell proliferation, migration and
      invasion, inducing cell apoptosis and reversing the EMT process in HuCCT1 and
      CCLP1 cells. Collectively, our data illustrated that lncRNA CCAT2 played an
      oncogenic role in CCA and may offer a potential therapeutic target for treating
      this fatal disease.

PMID- 29329035
TI  - Esterification of trans-aconitic acid improves its anti-inflammatory activity in
      LPS-induced acute arthritis.
AB  - trans-Aconitic acid (TAA) is an abundant constituent in the leaves of Echinodorus
      grandiflorus, a medicinal plant used to treat rheumatoid arthritis in Brazil.
      Esterification was explored as a strategy to increase lipophilicity and
      biopharmaceutical properties of TAA, a highly polar tricarboxylic acid. We herein
      report the synthesis of TAA esters via Fischer esterification with ethanol, n
      butanol and n-octanol. The reaction kinetics was investigated to produce mono-,
      di- and tri- derivatives. Mono- and diesters of TAA were obtained as a mixture of
      positional isomers, whereas the triesters were recovered as pure compounds. The
      obtained esters were screened in a model of acute arthritis induced by the
      injection of LPS in the knee joint of Swiss mice. The diesters were the most
      active compounds, regardless of the alcohol employed in the reaction, whereas
      bioactivity of the derivatives improved by increasing the length of the aliphatic
      chain of the alcohol employed in esterification. In general, the esters showed
      higher potency than TAA. When administered orally to mice at doses of 0.017-172.3
      MUmol/Kg, the diethyl, di-n-butyl and di-n-octyl esters of TAA reduced the
      cellular infiltration into the knee joint, especially of neutrophils. The study
      identified diesters of TAA as potential useful derivatives for the management of
      rheumatoid arthritis and other inflammatory diseases.

PMID- 29329036
TI  - Crocin improves the proliferation and cytotoxic function of T cells in children
      with acute lymphoblastic leukemia.
AB  - OBJECTIVE: Immunotherapy is important to improve the survival of children with
      acute lymphoblastic leukemia (ALL). This study aimed to assess the effects of
      crocin on the proliferation and function of T cells isolated from children with
      ALL. METHODS: The mononuclear cells were isolated from peripheral blood of
      children with ALL and then treated with different final concentrations of crocin.
      The levels of different cytokines secreted by T cells and the ratio of CD4 and
      CD8 were measured. Tail DNA% (TDNA), Tail moment (TM), Tail length (TL) and
      sister chromatid exchange (SCE) were detected to assess DNA damage of T cells.
      RESULTS: Crocin significantly promoted T cell proliferation and the secretion of
      IL-2 and IL-4 in a concentration dependent manner. In addition, crocin increased
      CD4/CD8 ratio of T subset. Crocin itself caused no significant damage to T cells
      but reduced DNA damage in T cells treated with Ara-C. CONCLUSIONS: Crocin could
      improve the proliferation and cytotoxic function of T cells, and reduce DNA
      damage caused by Ara-C.

PMID- 29329037
TI  - Phloem function: a key to understanding and manipulating plant responses to
      rising atmospheric [CO2]?
AB  - Increasing atmospheric carbon dioxide concentration ([CO2]) directly stimulates
      photosynthesis and reduces stomatal conductance in C3 plants. Both of these
      physiological effects have the potential to alter phloem function at elevated
      [CO2]. Recent research has clearly established that photosynthetic capacity is
      correlated to vascular traits associated with phloem loading and water transport,
      but the effects of elevated [CO2] on these relationships are largely unexplored.
      Plants also employ different strategies for loading sucrose and other sugars into
      the phloem, and there is potential for species with different phloem loading
      strategies to respond differently to elevated [CO2]. Recent research manipulating
      sucrose transporters and other key enzymes with roles in phloem loading show
      promise for maximizing crop performance in an elevated [CO2] world.

PMID- 29329038
TI  - Hallucinations as a presenting complaint in emergency departments: Prevalence,
      diagnosis, and costs.
AB  - Hallucinations occur in the context of many disorders. When experienced as
      distressing, they are a likely cause of presentation to emergency departments.
      Knowledge about the rates, diagnoses, and associated costs of hallucinations in
      emergency departments however is currently lacking. In this study, we analysed
      patients' presenting complaints in Western Australia's Emergency Department Data
      Collection dataset during a two year period (n = 1,798,754). Visits to emergency
      departments because of distressing hallucinations were more common than
      previously assumed. Hallucinations (auditory, visual, undifferentiated modality)
      accounted for 1.8% of all mental health-related presentations and 0.09% of all
      general health presentations (84.7 per 100,000 persons). Psychotic disorders
      accounted for a third of all presentations, and hallucinations without a clear
      medical or psychiatric cause represented 17% of the sample. Hallucination
      presentations had significantly prolonged lengths of stay compared to other
      mental health presentations (15 vs 7.5h, p < 0.001) and were linked to frequent
      re-admissions (average of 7.4 visits per year). Cost estimates revealed that
      hallucinations were in the top-10 most costly mental health complaint, and twice
      as costly to treat as delusions. Altogether, the service utilisation and care
      needs of people with distressing hallucinations outside of mental health services
      appear much larger than usually estimated.

PMID- 29329039
TI  - An investigation into the drivers of avolition in schizophrenia.
AB  - Over a century of research has documented that avolition is a core symptom in
      schizophrenia. However, the drivers of avolition remain unclear. Conceptually,
      there are at least two potential mutually compatible drivers that could cause
      avolition in schizophrenia. First, people with schizophrenia might have
      differences in preferences that result in less goal-directed behavior than non
      clinical populations (preference-differences). Second, people with schizophrenia
      might have difficulty translating their preferences into manifest behavior at
      rates similar to non-clinical populations (psychological-inertia). In the present
      work, we modified and validated a well-validated paradigm from the
      motivation/decision making literature to compare levels of preference-differences
      and psychological-inertia. To measure preference-differences, people with and
      without schizophrenia choose between a lower-valenced and higher-valenced image.
      We measured the rate at which the normatively lower-valenced image was preferred.
      To measure psychological-inertia, both groups were given the opportunity to
      volitionally switch from a lower-valenced image and view a higher-valenced image.
      Contrary to expectations, people with schizophrenia did not differ on either
      preference-differences or psychological-inertia. Statistical analysis revealed
      that the possibility of a Type II error for even a weak effect was small. The
      present data suggest new avenues for research investigating mechanisms underlying
      avolition and clinical interventions targeting avolition in schizophrenia.

PMID- 29329041
TI  - Thiol/disulphide homeostasis in bipolar disorder.
AB  - Bipolar disorder (BD) patients have increased oxidative stress, which can disturb
      thiol/disulphide homeostasis, causing disulphide formation. The aim of the study
      is to investigate dynamic thiol/disulphide (SH/SS) homeostasis in BD patients,
      which is a novel evaluation method of oxidative status. Ninety-four BD patients
      (50 in the manic episode and 44 in remission) and 44 healthy controls were
      included in the study. Blood serum native thiol (SH) and total thiol (ToSH)
      concentrations were measured in a paired test. The half value of the difference
      between native thiol and total thiol concentrations was calculated as the
      disulphide (SS) bond amount. Serum native thiol levels of the mania group were
      found to be lower than the remission and the control groups. There was a
      significant difference between the remission group and the control group in terms
      of native thiol. Serum total thiol level was lower in mania group than the
      control group. Detection of oxidative molecules for BD could be helpful,
      especially in treatment, follow-up periods and reducing morbidity. The results of
      our study besides the data available in the literature support that thiol and
      disulphide levels are useful markers for BD and promising therapeutic targets in
      terms of future pharmacological modulation.

PMID- 29329040
TI  - Do adverse life events at first onset of auditory verbal hallucinations influence
      subsequent voice characteristics? Results from an epidemiological study.
AB  - Understanding what happens at first onset of auditory verbal hallucinations
      (AVHs) is extremely important on a clinical and theoretical level. Previous
      studies have only focused on age with regard to first onset of AVHs. In the
      current epidemiological study, we examined a number of aspects relating to first
      onset of AVHs, such as the role of adverse life events at first onset of AVHs on
      symptom severity and general mental health. For this purpose, we compared
      participants who reported adverse life events at first onset of AHVs (adverse
      trigger group; N = 76) to those that did not report any specific events at first
      onset of AVHs (no-adverse-trigger group; N = 59) on a large array of variables.
      Results showed that AVHs in the adverse-trigger group were experienced as more
      emotional compared to the no-adverse-trigger group. In addition, the adverse
      trigger group more often reported hallucinations in other (non-auditory) sensory
      modalities (e.g. visual) compared to the no-adverse-trigger group. Furthermore,
      the adverse-trigger group reported poorer general mental health, reported having
      contact with mental health professionals more often, and also reported more
      frequently taking medication for psychological problems in general. The
      implications of these findings are discussed.

PMID- 29329042
TI  - Assessment of the efficacy of omega-3 fatty acids on metabolic and inflammatory
      parameters in patients with schizophrenia taking clozapine and sodium valproate.
AB  - Omega-3 fatty acid (FA) supplementation has been reported to improve several
      cardio-metabolic risk factors. We aimed to assess the efficacy of omega-3 fatty
      acids on metabolic and inflammatory indices in patients with schizophrenia who
      were taking clozapine and sodium valproate. All patients were on a stable dose of
      300-400mg of clozapine for 3 months. Subjects were randomized to treatment with
      either omega-3 fatty acid (4gr/day) or a placebo for 8 weeks. Height, weight,
      abdominal circumference, serum lipid profile, fasting blood glucose (FBG), and
      serum high sensitivity-C-reactive protein (hs-CRP) were determined at baseline
      and after 8 weeks of treatment. Fifty six subjects were recruited into the study.
      Patients with schizophrenia who were in the group receiving omega-3 FA capsules
      had an improvement in some anthropometric indices including weight, BMI, wrist
      and waist circumference, compared to the placebo group. Only changes in waist
      circumferences remained significantly different after adjustment for serum fasted
      TG. Our results showed omega-3 FA supplementation can improve some anthropometric
      indices in patients with schizophrenia who are taking clozapine pharmacotherapy.

PMID- 29329043
TI  - Impact of synthetic cannabinoid use on hospital stay in patients with bipolar
      disorder versus schizophrenia, or other psychotic disorders.
AB  - Synthetic cannabinoid products have become popular and have led to an increased
      number of patients presenting to emergency departments and psychiatric hospitals.
      The purpose of this study was to evaluate the impact of synthetic cannabinoid use
      at admission on length of stay and doses of antipsychotics at discharge in
      individuals with bipolar disorder, schizophrenia and other psychotic disorders.
      We retrospectively examined medical records of 324 inpatients admitted from
      January 2014 to July 2015. We found that synthetic cannabinoid use predicted
      length of stay and antipsychotic dose using structural equation modeling.
      Further, the association of synthetic cannabinoid use with length of stay was
      partly mediated by antipsychotic dose. These associations were independent of
      specific diagnosis. In conclusion, patients with bipolar disorder, schizophrenia,
      or other psychotic disorders who reported synthetic cannabinoid use at admission
      had shorter length of stay and received lower doses of antipsychotics,
      irrespective of clinical diagnoses.

PMID- 29329044
TI  - Neurological soft signs in bipolar and unipolar disorder: A case-control study.
AB  - Neuropsychiatric disorders are associated with neurological soft signs (NSS),
      including motor, sensory, and inhibitory dysfunction. The present study aims at
      determining the prevalence of NSS and explore the association of sociodemographic
      characteristics with the occurrence of NSS in patients with bipolar disorder and
      unipolar depression compared to healthy controls. A case-control study included a
      sample of 50 bipolar and unipolar patients and 50 healthy controls. NSS subscales
      of the Neurological Evaluation Scale (NES) were administered to each participant.
      Significant differences were found in the total NES score, motor coordination,
      sensory integration, sequence of complex motor act and other subscales among the
      three groups. Compared with healthy controls, patients with bipolar disorder
      showed significantly more total NSS signs, motor coordination signs and sensory
      integration signs. When compared with patients with unipolar disorder, patients
      with bipolar disorder showed significantly more sensory integration signs and a
      trend of difference in the sequencing of complex motor acts and other subscales.
      Our findings suggest that NSS may be specifically associated with bipolar
      disorder but not unipolar depression. The specificity of NSS expression has the
      potential to help the discrimination of bipolar disorder from disorders less
      likely to have a neurodevelopmental component such as major depression.

PMID- 29329045
TI  - Increased depression symptom score in newly diagnosed type 2 diabetes patients.
AB  - The aim was to investigate the association between diabetes duration and
      depressive symptoms in type 2 diabetes. The DIAREG registry used data of a
      nationwide general medicine practice database (Disease Analyzer, Germany)
      augmented by prospective data from patient reported outcomes (PRO) including
      Center of Epidemiological Studies Depression Scale (CES-D: <16 vs. >=16) and the
      SF-36. Multiple logistic regression models were used to investigate the
      association of diabetes duration with PROs. Overall, 1807 type 2 diabetes
      patients were registered in 108 practices. From 270 (15%) patients complete PRO
      could be collected, which were similar with respect to age, sex, body mass index,
      HbA1c, diabetes duration and treatment to patients with incomplete data
      (p>=0.05). Patients with a longer diabetes duration (reference: <2 years)
      displayed a significantly increased odds of having no indication of depression
      (CES-D <16: 66%) (Odds Ratio, 95%CI: 2-<5 years: 5.9, 1.2-29.6; 5-<10 years: 6.2,
      1.3-28.7; >=10 years: 5.6, 1.2-23.1), after adjusting for age, sex, BMI, diabetes
      complications, antidepressants and glucose-lowering treatment. Patients with <2
      years diabetes duration also exhibited a significantly decreased mean mental
      component score (SF-36: <2 years: 50, 2-<5 years: 69). In type 2 diabetes with a
      short duration an increased depressive symptom score was observed.

PMID- 29329046
TI  - Social distance toward people with schizophrenia is associated with favorable
      understanding and negative stereotype.
AB  - Previous studies have suggested the consequence of mental health-related public
      stigma: the problem of knowledge may develop into problem of attitude and
      behaviour. However, this has not been directly explored in a longitudinal study.
      As the secondary analysis from our previous randomized controlled trial (RCT) for
      219 participants who completed the survey at the 12-month follow-up, we aimed to
      investigate whether the knowledge and attitude components of stigma toward people
      with schizophrenia affect each other. At baseline and at 12 months, three types
      of stigma scales were measured: favorable understanding, negative stereotype, and
      social distance toward people with schizophrenia. A structured equation model was
      fitted to the trajectory of stigma scales taking into account the effect of the
      other stigma components and the interventions. The results showed that greater
      social distance toward people with schizophrenia at baseline was associated with
      less favorable understanding and more negative stereotype at the 12-month follow
      up. This was not in line with the existing consequences from the previous
      studies; however, in line with the recent RCTs showing that social contact is the
      most effective intervention to reduce stigma. Future observational studies with a
      larger sample size are needed to clarify this relationship further.

PMID- 29329047
TI  - The connection between subjective nearness-to-death and depressive symptoms: The
      mediating role of meaning in life.
AB  - Depression is characterized by a wide range of emotional, cognitive, and physical
      symptoms. Two prominent features of depressive symptoms are a sense that life has
      no meaning on the one hand, and that life is not worth living on the other hand.
      In recent years, the subjective perception of how close one feels to his/her
      death has gained importance as a significant factor associated with various
      aspects of physical and psychological well-being. Thus, the current study
      examined the connection between subjective nearness-to-death, meaning in life,
      and depressive symptoms, and assessed whether meaning in life mediates the
      connection between subjective nearness-to-death and depressive symptoms. Data was
      collected from 268 participants between the ages of 28 and 74 (mean age = 46.75),
      who completed measures of subjective nearness-to-death, meaning in life, and
      depressive symptoms. Results yielded a significant positive connection between
      subjective nearness-to-death and depressive symptoms, as well as a negative
      connection between meaning in life and depressive symptoms. Moreover, meaning in
      life was found to mediate the connection between subjective nearness-to-death and
      depressive symptoms. Findings are discussed in light of the Terror Management
      Theory, and potential clinical implications are suggested.

PMID- 29329048
TI  - Characterizing anger-related affect in individuals with posttraumatic stress
      disorder using ecological momentary assessment.
AB  - This study employed secondary analyses of existing ecological momentary
      assessment (EMA) data to characterize hostile and irritable affect in the day-to
      day experience of 52 smokers with, and 65 smokers without, posttraumatic stress
      disorder (PTSD). EMA monitoring occurred over a mean of 8.2 days, and
      participants responded to an average of 2.8 random prompts/day. Analyses included
      Wilcoxon rank sum tests of group differences, and path analyses of cross-lagged
      multilevel models. Participants with PTSD endorsed a significantly higher
      proportion of total EMA entries indicating hostile affect and irritable affect
      than did individuals without PTSD. Cross-lagged analyses indicated that over a
      period of hours, PTSD symptoms significantly predicted subsequent hostile and
      irritable affect, but hostile and irritable affect did not predict subsequent
      PTSD symptoms. Findings suggest that day-to-day exposure to PTSD-related trauma
      cues may contribute to chronically elevated levels of anger-related affect. Such
      heightened affective arousal may, in turn, underlie an increased risk for verbal
      or physical aggression, as well as other health and quality-of-life related
      impairments associated with PTSD. Clinical implications include conceptualizing
      anger treatment in the broader context of trauma history and symptoms, and
      specifically targeting physiological arousal and maladaptive hostile cognitions
      triggered by trauma reminders in patients with PTSD.

PMID- 29329049
TI  - The traumatized body: Long-term PTSD and its implications for the orientation
      towards bodily signals.
AB  - Orientation to bodily signals is defined as the way somatic sensations are
      attended, perceived and interpreted. Research suggests that trauma exposure,
      particularly the pathological reaction to trauma (i.e., PTSD), is associated with
      catastrophic and frightful orientation to bodily signals. However, little is
      known regarding the long-term ramifications of trauma exposure and PTSD for
      orientation to bodily signals. Less is known regarding which PTSD symptom cluster
      manifests in the 'somatic route' through which orientation to bodily signals is
      altered. The current study examined the long-term implications of trauma and PTSD
      trajectories on orientation to bodily signals. Fifty-nine ex-prisoners of war (ex
      POWs) and 44 controls were assessed for PTSD along three time-points (18, 30 and
      35 years post-war). Orientation to bodily signals (pain catastrophizing and
      anxiety sensitivity-physical concerns) was assessed at T3. Participants with a
      chronic PTSD trajectory had higher pain catastrophizing compared to participants
      with no PTSD. PTSD symptom severity at T2 and T3 mediated the association between
      captivity and orientation. Among PTSD symptom clusters, hyperarousal at two time
      points and intrusion at three time-point mediated the association between
      captivity and orientation. These findings allude to the cardinal role of long
      term PTSD in the subjective experience of the body following trauma.

PMID- 29329050
TI  - Factors influencing the severity of behavioral phenotype in autism spectrum
      disorders: Implications for research.
AB  - The phenotypic heterogeneity of Autism Spectrum Disorders (ASD) presents
      particular research challenges in the assessment of symptom severity, while the
      standardized Autism Diagnostic Observation Schedule (ADOS) scores present a
      severity metric, namely calibrated severity scores (CSS) that are relatively
      impervious to individual characteristics. To date, no studies have examined the
      convergent validity of CSS in Chinese sample populations. The present study
      investigated the validity of the ADOS-CSS using a sample of 321 children aged 2
      18 years with ASD, and developed upon existing literature examining the influence
      of non-ASD-specific characteristics on other types of measures including Autism
      Diagnostic Interview-Revised (ADI-R), Social Responsiveness Scale (SRS), and
      Vineland Adaptive Behavior Scales (VABS). As expected, the findings revealed that
      the CSS were less influenced than ADOS-RAW scores by the demographic and
      developmental-level variables. Moreover, compared to the ADOS-CSS, the ADI-R, SRS
      and VABS were still strongly correlated with confounding factors, such as
      chronological age, intelligence quotients, and language-level. The results of
      this study corroborate the utilization of CSS as a more valid indicator of ASD
      severity than raw scores from ADOS and other instruments.

PMID- 29329052
TI  - Efficient and cost-effective generation of hepatocyte-like cells through
      microparticle-mediated delivery of growth factors in a 3D culture of human
      pluripotent stem cells.
AB  - Biomedical application of human pluripotent stem cell-derived hepatocyte-like
      cells (hPSC-HLCs) relies on efficient large-scale differentiation, which is
      commonly performed by a suspension culture of three-dimensional (3D)
      multicellular spheroids in bioreactors. However, this approach requires large
      amounts of growth factors (GFs) and the need to overcome limited diffusional
      transport posed by the inherent 3D structure of hPSC spheroids. Here, we have
      hypothesized that localized delivery of GFs by incorporation of GF-laden
      degradable polymeric microparticles (MPs) within the hPSC spheroids would
      circumvent such limitations. In this study, GFs for hepatocytic differentiation
      were encapsulated in gelatin-coated poly (l-lactic acid)/poly (DL-lactic-co
      glycolic acid) (PLLA/PLGA) MPs which were subsequently incorporated into the hPSC
      spheroids. Gene expression analyses demonstrated that MP delivery of the GFs
      resulted in similar expression levels of hepatocytic markers despite the use of
      10-fold less total GFs. The differentiated HLCs in the MP group exhibited
      ultrastructure and functional characteristics comparable with the conventional
      soluble GF group. The generated HLCs in the MP group were successfully engrafted
      in an acute liver injury mouse model and maintained hepatocytic function after
      implantation. These results suggested that sustained and localized delivery of
      GFs using MPs might offer a novel approach towards scalable technologies for
      hepatocytic differentiation and engineer a better 3D microenvironment for cells.

PMID- 29329051
TI  - Non-genetic engineering of cytotoxic T cells to target IL-4 receptor enhances
      tumor homing and therapeutic efficacy against melanoma.
AB  - Adoptive transfer of cytotoxic T lymphocytes (CTLs) has been used as an
      immunotherapy in melanoma. However, the tumor homing and therapeutic efficacy of
      transferred CTLs against melanoma remain unsatisfactory. Interleukin-4 receptor
      (IL-4R) is commonly up-regulated in tumors including melanoma. Here, we studied
      whether IL-4R-targeted CTLs exhibit enhanced tumor homing and therapeutic
      efficacy against melanoma. CTLs isolated from mice bearing melanomas were non
      genetically engineered with IL4RPep-1, an IL-4R-binding peptide, using a membrane
      anchor composed of dioleylphosphatidylethanolamine. Compared to control CTLs, IL
      4R-targeted CTLs showed higher binding to melanoma cells and in vivo tumor
      homing. They also exerted a more rapid and robust effector response, including
      increased cytokine secretion and cytotoxicity against melanoma cells and enhanced
      reprogramming of M2-type macrophages to M1-type macrophages. Moreover, IL-4R
      targeted CTLs efficiently inhibited melanoma growth and reversed the
      immunosuppressive tumor microenvironment. These results suggest that non
      genetically engineered CTLs targeting IL-4R have potential as an adoptive T cell
      therapy against melanoma.

PMID- 29329053
TI  - Long Term Safety Area Tracking (LT-SAT) with online failure detection and
      recovery for robotic minimally invasive surgery.
AB  - Despite the benefits introduced by robotic systems in abdominal Minimally
      Invasive Surgery (MIS), major complications can still affect the outcome of the
      procedure, such as intra-operative bleeding. One of the causes is attributed to
      accidental damages to arteries or veins by the surgical tools, and some of the
      possible risk factors are related to the lack of sub-surface visibilty. Assistive
      tools guiding the surgical gestures to prevent these kind of injuries would
      represent a relevant step towards safer clinical procedures. However, it is still
      challenging to develop computer vision systems able to fulfill the main
      requirements: (i) long term robustness, (ii) adaptation to environment/object
      variation and (iii) real time processing. The purpose of this paper is to develop
      computer vision algorithms to robustly track soft tissue areas (Safety Area, SA),
      defined intra-operatively by the surgeon based on the real-time endoscopic
      images, or registered from a pre-operative surgical plan. We propose a framework
      to combine an optical flow algorithm with a tracking-by-detection approach in
      order to be robust against failures caused by: (i) partial occlusion, (ii) total
      occlusion, (iii) SA out of the field of view, (iv) deformation, (v) illumination
      changes, (vi) abrupt camera motion, (vii), blur and (viii) smoke. A Bayesian
      inference-based approach is used to detect the failure of the tracker, based on
      online context information. A Model Update Strategy (MUpS) is also proposed to
      improve the SA re-detection after failures, taking into account the changes of
      appearance of the SA model due to contact with instruments or image noise. The
      performance of the algorithm was assessed on two datasets, representing ex-vivo
      organs and in-vivo surgical scenarios. Results show that the proposed framework,
      enhanced with MUpS, is capable of maintain high tracking performance for extended
      periods of time ( ? 4 min - containing the aforementioned events) with high
      precision (0.7) and recall (0.8) values, and with a recovery time after a failure
      between 1 and 8 frames in the worst case.

PMID- 29329054
TI  - Relationship between sedentary behavior and depression: A mediation analysis of
      influential factors across the lifespan among 42,469 people in low- and middle
      income countries.
AB  - BACKGROUND: Sedentary behavior (SB) is associated with diabetes, cardiovascular
      disease and low mood. There is a paucity of multi-national research investigating
      SB and depression, particularly among low- and middle-income countries. This
      study investigated the association between SB and depression, and factors which
      influence this. METHODS: Cross-sectional data were analyzed from the World Health
      Organization's Study on Global Ageing and Adult Health. Depression was based on
      the Composite International Diagnostic Interview. The association between
      depression and SB (self-report) was estimated by multivariable linear and
      logistic regression analyses. Mediation analysis was used to identify influential
      factors. RESULTS: A total of 42,469 individuals (50.1% female, mean 43.8 years)
      were included. People with depression spent 25.6 (95%CI8.5-42.7) more daily
      minutes in SB than non-depressed participants. This discrepancy was most notable
      in adults aged >= 65y (35.6min more in those with depression). Overall, adjusting
      for socio-demographics and country, depression was associated with a 1.94
      (95%CI1.31-2.85) times higher odds for high SB (i.e., >= 8h/day). The largest
      proportion of the SB-depression relationship was explained by mobility
      limitations (49.9%), followed by impairments in sleep/energy (43.4%),
      pain/discomfort (31.1%), anxiety (30.0%), disability (25.6%), cognition (16.1%),
      and problems with vision (11.0%). Other health behaviors (physical activity,
      alcohol consumption, smoking), body mass index, and social cohesion did not
      influence the SB-depression relationship. CONCLUSION: People with depression are
      at increased risk of engaging in high levels of SB. This first multi-national
      study offers potentially valuable insight for a number of hypotheses which may
      influence this relationship, although testing with longitudinal studies is
      needed.

PMID- 29329055
TI  - Altered brain structure in women with premenstrual syndrome.
AB  - BACKGROUND: Functional brain abnormalities have been noted in premenstrual
      syndrome (PMS). However, the brain structural alterations related to PMS remain
      unclear. This study aimed to identify possible abnormalities in gray matter (GM)
      volumes and structural covariance patterns among PMS patients. METHODS:
      Structural magnetic resonance imaging data were obtained from 20 PMS patients and
      20 healthy controls. Voxel-based morphometry (VBM) analysis was applied to
      examine GM volumes changes between the two groups. Receiver operating
      characteristic (ROC) curve was used to investigate the most reliable biomarker
      for distinguishing PMS patients from health controls based on the intergroup
      differences. Correlation analysis was then performed to assess relationships
      between the daily rating of severity of problems (DRSP) and abnormal brain
      regions. Finally, the regions identified from VBM analysis were served as seeds
      to characterize the whole-brain structural covariance patterns. RESULTS: Compared
      with healthy controls, PMS patients showed increased GM volumes in the
      precuneus/posterior cingulate cortex (precuneus/PCC) and thalamus, and decreased
      GM volumes in the insula. The precuneus/PCC exhibited the highest classification
      power by ROC analysis and positively correlated with the DRSP. Moreover,
      different patterns of structural covariance in the two groups were mainly located
      in the dorsolateral prefrontal cortex, anterior cingulate cortex, angular gyrus
      and hippocampus. LIMITATIONS: This study is limited by a small sample and narrow
      age range of participants. CONCLUSIONS: Our findings may provide preliminary
      evidence for brain morphology alterations in PMS patients and contribute to a
      better understanding of the pathophysiology of PMS.

PMID- 29329056
TI  - Subjective and objective sleep discrepancy in symptomatic bipolar disorder
      compared to healthy controls.
AB  - BACKGROUND: Bipolar disorder (BD) is associated with sleep misperception. The
      objective of this study was to investigate the correlation between subjective and
      objective measures of sleep in persons with symptomatic bipolar disorder (BDS)
      compared to healthy controls (HC). METHODS: We studied 24 BDS and 30 HC subjects
      similar in age, race and sex. Subjective sleep was measured with Pittsburgh Sleep
      Quality Index (PSQI) and objective sleep with 7-days of actigraphy. Absolute
      discrepancy variables were calculated by subtracting objective sleep latency (SL)
      and total sleep time (TST) on actigraphy from their respective subjective
      estimates from PSQI. Mood symptoms were measured with Young Mania Rating Scale
      and Hamilton Depression Rating Scale. RESULTS: In the BDS group, subjective TST
      did not significantly correlate with objective TST, while it correlated in the HC
      group. The BDS group had significantly higher absolute discrepancy between
      subjective and objective SL and TST compared to the HC group. Multivariable
      regression analysis showed that severity of depression was associated with
      greater absolute discrepancy between subjective and objective TST within the BDS
      group. LIMITATIONS: Subjects are from a tertiary care center and were on
      medications for treatment of BD symptoms. CONCLUSION: There is low correlation
      between subjective and objective TST in BDS subjects and more severe depressive
      symptoms are associated with greater absolute discrepancy in TST. Objective
      rather than subjective measures of sleep, such as actigraphy, may be needed to
      evaluate sleep in BD subjects. Cognitive-behavioral interventions to address
      sleep misperception and associated depressed mood may be indicated in BD.

PMID- 29329057
TI  - Chronic corticosterone-induced depression mediates premature aging in rats.
AB  - BACKGROUND: Stress hormones such as corticosterone (CORT) play an essential role
      in the development of depression. Chronic CORT administration has been shown to
      induce dysfunction in the hypothalamic-pituitary-adrenal axis leading to
      depression, which was in turn associated with accelerated aging. However, the
      effect of CORT administration on aging remains unclear. METHODS: Rats were
      acclimatized for 1 week and then injected daily with CORT (40mg/kg) or vehicle (n
      = 10 each) for 21 consecutive days. Age-related indexes were then compared
      between CORT-treated rats and control rats. RESULTS: CORT induced affective
      behaviors indicative of depressive-like symptoms in rats, including reduced
      sucrose preference and increased immobility time in the forced swimming test.
      CORT-treated rats exhibited telomere shortening, possibly contributing to
      decreased telomerase activity and down-regulated expression of telomere-binding
      factor 2, correlated with enhanced oxidative damage. This was associated with
      inhibition of sirtuin 3 leading to reduced activities of superoxide dismutase 2
      and glutathione reductase. CORT-treated rats showed degenerated mitochondrial
      functions represented by decreased adenosine triphosphate production, decreased
      nicotinamide adenine dinucleotide+ content, and decreased activity of
      nicotinamide phosphoribosyltransferase. LIMITATIONS: The group sample sizes were
      small, and only male rats and a single dose level of CORT were used. CONCLUSION:
      These findings demonstrate that CORT-induced depression may be involved in
      mediating the pathophysiology of premature aging in rats.

PMID- 29329058
TI  - Association of comorbid personality disorders with clinical characteristics and
      outcome in a randomized controlled trial comparing two psychotherapies for early
      onset persistent depressive disorder.
AB  - BACKGROUND: Persistent depressive disorder (PDD) is associated with high rates of
      comorbid personality disorders (PD). The association of comorbid PD and clinical
      characteristics has not been systematically studied in PDD. Results regarding
      effects on treatment outcome are heterogeneous. METHODS: We analyzed the
      association of comorbid personality disorders with clinical characteristics and
      outcome in a randomized controlled trial comparing the disorder-specific
      Cognitive Behavioral Analysis System of Psychotherapy (CBASP) with nonspecific
      supportive psychotherapy (SP) in patients with early-onset PDD. The main outcome
      measure was the Hamilton Rating Scale for Depression (HRSD-24). Further baseline
      measures were comorbid axis-I diagnoses (SCID-I), quality of life (QLDS), global
      functioning (GAF), interpersonal problems (IIP-64) and childhood maltreatment
      (CTQ). RESULTS: Out of the 268 patients, 103 (38.4%) met criteria for at least
      one PD. PD was associated with higher rates of axis I comorbidities (mainly
      anxiety disorders) and interpersonal problems (patients with PD were more
      vindictive, more self-sacrificing, less assertive and more inhibited socially
      than patients without PD). There was no significant main effect of PD on
      treatment outcome and no significant interaction between PD and treatment group.
      LIMITATIONS: The main limitation was the exclusion of patients with certain
      personality disorders (antisocial, schizotypal, and borderline personality
      disorders). Furthermore, the study was underpowered to find interaction effects
      of small size. CONCLUSION: Persistently depressed patients with and without
      comorbid PD primarily seemed to differ in the rate of axis I comorbidity and the
      severity of interpersonal problems. Treatment outcomes appear to be not
      significantly affected by the presence of PD.

PMID- 29329059
TI  - Amyloid burden and incident depressive symptoms in preclinical Alzheimer's
      disease.
AB  - BACKGROUND: Relationships between depression and Alzheimer's disease (AD) may
      become clearer if studied in preclinical AD where dementia is not present.
      METHOD: The aim of this study was to evaluate prospectively, relationships
      between brain amyloid-beta (Abeta), depressive symptoms and screen positive
      depression in cognitively normal (CN) older adults. Depressive symptoms were
      measured with the Geriatric Depression Inventory (GDS-15) in CN adults from the
      Australian Imaging Biomarkers and Lifestyle (AIBL) study without depression at
      baseline and classified as having abnormally high (Abeta+; n = 136) or low (Abeta
      ; n = 449) Abeta according to positron emission tomography at 18-month intervals
      over 72 months. RESULTS: Incident cases of screen positive depression were not
      increased in Abeta+ CN adults although small increases in overall depressive
      symptoms severity (d = - 0.25; 95% CI, - 0.45, - 0.05) and apathy-anxiety
      symptoms (d = - 0.28; 95% CI - 0.48, - 0.08) were. LIMITATIONS: As the AIBL
      sample is an experimental sample, no individuals had severe medical illnesses or
      significant psychiatric disorders. Additionally, individuals who had evidence of
      screen-positive depression at screening were excluded from enrolment in the AIBL
      study. Thus, the current data can be considered only as providing a foundation
      for understanding relationships between Abeta and depression in preclinical AD.
      CONCLUSIONS: These results suggest that the presence of a depressive disorder or
      even increased depressive symptoms are themselves unlikely to be a direct
      consequence of increasing Abeta. New depressive disorders presenting in CN older
      adults could therefore be investigated for aetiologies beyond AD.

PMID- 29329060
TI  - Affective and cognitive reactivity to mood induction in chronic depression.
AB  - BACKGROUND: Chronic depression (CD) is strongly associated with childhood
      maltreatment, which has been proposed to lead to inefficient coping styles that
      are characterized by abnormal affective responsiveness and dysfunctional
      cognitive attitudes. However, while this notion forms an important basis for
      psychotherapeutic strategies in the treatment of CD, there is still little direct
      empirical evidence for a role of altered affective and cognitive reactivity in
      CD. The present study therefore experimentally investigated affective and
      cognitive reactivity to two forms of negative mood induction in CD patients
      versus a healthy control sample (HC). METHODS: For the general mood induction
      procedure, a combination of sad pictures and sad music was used, while for
      individualized mood induction, negative mood was induced by individualized
      scripts with autobiographical content. Both experiments included n = 15 CD
      patients versus n = 15 HC, respectively. Interactions between affective or
      cognitive reactivity and group were analyzed by repeated measurements ANOVAs.
      RESULTS: General mood induction neither revealed affective nor cognitive
      reactivity in the patient group while the control group reported the expected
      decrease of positive affect [interaction (IA) affective reactivity x group: p =
      .011, cognitive reactivity x group: n.s.]. In contrast, individualized mood
      induction specifically increased affective reactivity (IA: p = .037) as well as
      the amount of dysfunctional cognitions in patients versus controls (IA: p =
      .014). LIMITATIONS: The experiments were not balanced in a crossover design,
      causal conclusions are thus limited. Additionally, the differences to non-chronic
      forms of depression are still outstanding. CONCLUSIONS: The results suggest that
      in patients with CD, specific emotional activation through autobiographical
      memories is a key factor in dysfunctional coping styles. Psychotherapeutic
      interventions aimed at modifying affective and cognitive reactivity are thus of
      high relevance in the treatment of CD.

PMID- 29329061
TI  - Experimental effects of acute exercise duration and exercise recovery on mood
      state.
AB  - OBJECTIVE: Accumulating evidence suggests that, in addition to various
      psychosocial parameters, affective responses to exercise play an important role
      in subserving future exercise behavior. This study comprehensively evaluated
      whether acute exercise duration and recovery period influenced the relationship
      between moderate-intensity walking exercise and mood profile. METHOD: We employed
      a randomized controlled cross-over trial. Participants completed two laboratory
      visits, separated by one-week. One of the visits involved a mood profile
      assessment with no exercise, while the other visit involved a mood profile
      assessment after an acute bout of exercise. Participants (N = 352; 22 per group;
      young [Mage = 21 yrs] healthy adults) were randomized into one of 16 experimental
      groups: 10, 20, 30, 45 or 60min bout of exercise coupled with either a 5, 15 or
      30min recovery period. The exercise bout was of moderate-intensity (40-59% of
      HRR). Mood profile was assessed from the POMS survey, considering subscales of
      depression, anger and hostility. RESULTS: For all three mood profile parameters,
      there was no evidence of a group x time interaction effect. However, the main
      effect for time was statistically significant for each mood parameter. These
      significant results demonstrate that, generally, exercise had a favorable effect
      on each of the mood profile, regardless of exercise duration and recovery period.
      In addition to the significant main effects for time, we also observed a
      significant main effect for group for the mood parameter hostility. With the
      exception of the group 13 (60min of exercise with 5min recovery) and the 3 groups
      that employed a 10-min bout of exercise (groups 1-3), all other experimental
      groups had a lower (better) hostility score after the exercise visit.
      CONCLUSIONS: Generally, exercise had a favorable effect on various mood profiles,
      regardless of exercise duration (between 10 and 60min) and recovery period
      (between 5 and 30min).

PMID- 29329062
TI  - Amygdala response to emotional faces in seasonal affective disorder.
AB  - BACKGROUND: Seasonal affective disorder (SAD) is characterized by seasonally
      recurring depression. Heightened amygdala activation to aversive stimuli is
      associated with major depressive disorder but its relation to SAD is unclear. We
      evaluated seasonal variation in amygdala activation in SAD and healthy controls
      (HC) using a longitudinal design targeting the asymptomatic/symptomatic phases of
      SAD. We hypothesized increased amygdala activation to aversive stimuli in the
      winter in SAD individuals (season-by-group interaction). METHODS: Seventeen SAD
      individuals and 15 HCs completed an implicit emotional faces BOLD-fMRI paradigm
      during summer and winter. We computed amygdala activation (SPM5) to an aversive
      contrast (angry & fearful minus neutral) and angry, fearful and neutral faces,
      separately. Season-by-group and main effects were evaluated using Generalized
      Least Squares. In SAD individuals, we correlated change in symptom severity,
      assessed with The Hamilton Rating Scale for Depression - Seasonal Affective
      Disorder version (SIGH-SAD), with change in amygdala activation. RESULTS: We
      found no season-by-group, season or group effect on our aversive contrast.
      Independent of season, SAD individuals showed significantly lower amygdala
      activation to all faces compared to healthy controls, with no evidence for a
      season-by-group interaction. Seasonal change in amygdala activation was unrelated
      to change in SIGH-SAD. LIMITATIONS: Small sample size, lack of positive valence
      stimuli. CONCLUSIONS: Amygdala activation to aversive faces is not increased in
      symptomatic SAD individuals. Instead, we observed decreased amygdala activation
      across faces, independent of season. Our findings suggest that amygdala
      activation to angry, fearful and neutral faces is altered in SAD individuals,
      independent of the presence of depressive symptoms.

PMID- 29329063
TI  - Seasonality of depressive symptoms in women but not in men: A cross-sectional
      study in the UK Biobank cohort.
AB  - BACKGROUND: We examined whether seasonal variations in depressive symptoms
      occurred independently of demographic and lifestyle factors, and were related to
      change in day length and/or outdoor temperature. METHODS: In a cross-sectional
      analysis of >150,000 participants of the UK Biobank cohort, we used the cosinor
      method to assess evidence of seasonality of a total depressive symptoms score and
      of low mood, anhedonia, tenseness and tiredness scores in women and men.
      Associations of depressive symptoms with day length and mean outdoor temperature
      were then examined. RESULTS: Seasonality of total depressive symptom scores,
      anhedonia and tiredness scores was observed in women but not men, with peaks in
      winter. In women, increased day length was associated with reduced reporting of
      low mood and anhedonia, but with increased reporting of tiredness, independent of
      demographic and lifestyle factors. Associations with day length were not
      independent of the average outdoor temperature preceding assessment. LIMITATIONS:
      This was a cross-sectional investigation - longitudinal studies of within-subject
      seasonal variation in mood are necessary. Outcome measures relied on self-report
      and measured only a subset of depressive symptoms. CONCLUSION: This large,
      population-based study provides evidence of seasonal variation in depressive
      symptoms in women. Shorter days were associated with increased feelings of low
      mood and anhedonia in women. Clinicians should be aware of these population-level
      sex differences in seasonal mood variations in order to aid recognition and
      treatment of depression and subclinical depressive symptoms.

PMID- 29329064
TI  - User acceptability of the diagnosis of prolonged grief disorder: How do
      professionals think about inclusion in ICD-11?
AB  - BACKGROUND: For the next edition of the International Statistical Classification
      of Diseases (ICD-11) it is proposed to include prolonged grief disorder as a new
      diagnosis. The diagnosis describes persistent intensive and disabling grief
      reactions to bereavement (WHO, 2016b). The aim of the present survey was to
      determine the extent to which the diagnosis is accepted by practitioners in the
      healthcare and psychosocial field. METHODS: A total of 2088 German-speaking
      professionals in the fields of psychotherapy, psychology, counselling, medicine
      and palliative care completed the online survey. RESULTS: 42.4% of the
      participants felt that the advantages of including the diagnosis outweigh the
      disadvantages, 32.9% came to the conclusion that there are more disadvantages.
      The remaining 24.7% stated that advantages and disadvantages are balanced. The
      proposed classification as separate diagnosis was supported by 24.8%, while 60.0%
      preferred alternatives (e.g. as subtype of adjustment disorder). Furthermore, a
      time criterion of at least 12 months was voted for considerably more frequently
      (49.2%) than the proposed 6 months (11.3%). Objections were predominantly
      expressed with regard to pathologization of normal grief and to the difficulty of
      adequate crosscultural application of the diagnosis. LIMITATIONS: Results are
      limited to predominantly German health-care professionals. The items did not
      undergo psychometric analyses. CONCLUSIONS: The disagreement about the diagnosis
      found in specialist literature is also reflected in the responses by the
      participants. The present results provide stimulation for future questions and
      validation studies carried out as part of the ICD revision.

PMID- 29329065
TI  - Factors associated with depression among homeless mothers. Results of the ENFAMS
      survey.
AB  - PURPOSE: Women are disproportionately likely to suffer from depression. This is
      especially true for those who experience socioeconomic hardship, such as
      homelessness. In France, among homeless mothers many are migrant. However, it is
      not clear whether risk factors associated with depression are specific for this
      group or the same as in the general population. Our objective was to describe
      socio-demographic, relational, living and housing conditions and health factors
      associated with depression among homeless mothers. METHODS: The ENFAMS survey,
      conducted via face-to-face bilingual interviews with a representative sample of
      homeless families in the Paris region (January-May 2013, n = 733 mothers).
      Mothers reported their socio-demographic characteristics, housing conditions
      including residential mobility, as well as physical and mental health. Depression
      was ascertained using the Composite International Diagnostic Interview (CIDI).
      Factors associated with mother's depression were studied in weighted Poisson
      regression models with robust error variance. RESULTS: The prevalence of
      depression among participating mothers was 28.8%. In multivariate analyses,
      depression was associated with fluency in French (PR = 1.88 95% CI 1.40; 2.51),
      suicide risk (PR = 2.26, 95% CI 1.82; 2.82), post-traumatic stress disorder (PR =
      1.97, 95% CI 1.50; 2.60), and unmet health needs (PR = 1.68, 95% CI 1.09; 2.57).
      CONCLUSIONS: Homeless mothers have high levels of depression and associated
      psychiatric comorbidities. Associated risk factors appear to be both specific for
      this group and shared with mothers in the general population. Improvements in the
      monitoring of mental health difficulties as well as access to appropriate medical
      care in this vulnerable population may help improve health and social outcomes.

PMID- 29329068
TI  - "Subcutaneous emphysema" is not always actually in the subcutaneous plane. A Case
      of subfascial emphysema after laparoscopy.

PMID- 29329066
TI  - Association of suicidal risk with ratings of affective temperaments.
AB  - BACKGROUND: Ratings of particular temperament-types with the TEMPS-A
      autoquestionnaire have been associated with suicidal risk, and combinations of
      such ratings may enhance the association. However, the predictive value of scores
      for individual temperaments and combinations remains to be quantified. METHOD: We
      evaluated associations of TEMPS-A ratings for anxious (anx), cyclothymic (cyc),
      dysthymic (dys), hyperthymic (hyp) and irritable (irr) temperaments, with a
      history of suicidal acts or reported suicidal ideation in 882 patients with
      bipolar (BD; n = 509), major depressive (MDD; n = 268) or anxiety (ANX; n = 105)
      disorders. RESULTS: With BD, scores for cyc and irr were highest and anx lowest;
      with MDD, dys scored highest, hyp lowest; anx was highest with ANX and MDD. Women
      (n = 497) had higher anx and cyc scores than men; scores for irr and hyp
      decreased with age. Scores for dys, anx, and cyc, were higher, and hyp lower,
      with greater HDRS21 depression ratings. Among 347 suicidal subjects (112 with
      attempts), cyc, dys, and irr scores were higher, hyp lower. Pooled score [cyc+
      dys+ irr - hyp] best distinguished subjects with suicide attempts versus
      nonsuicidal subjects, including in Receiver-Operating Characteristic (ROC)
      analysis (AUC for acts = 70.1% [64.9- 75.3]). Multivariable modeling associated
      suicidal acts with TEMPS-A [cyc+ dys+ irr - hyp] composite-score, depression
      severity, BD or MDD diagnosis, and older at illness-onset. CONCLUSIONS: Subjects
      with suicidal acts or ideation were best distinguished by composite TEMPS-A score
      [cyc+ dys+ irr - hyp]. These factors should help to identify those at suicidal
      risk.

PMID- 29329069
TI  - Supraclavicular brachial plexus block is an alternative to pectoral nerve block 1
      for contracture reconstruction post mastectomy.

PMID- 29329067
TI  - Case report: Iatrogenic brachial artery dissection with complete anterograde
      occlusion during elective arterial line placement.
AB  - INTRODUCTION: Brachial arterial catheters provide a more accurate reflection of
      central aortic arterial pressure compared to their radial counterparts. Although
      brachial arterial line complications are uncommon, we report a case of a rare
      iatrogenic brachial artery dissection with complete anterograde occlusion from
      elective arterial line placement. PRESENTATION OF CASE: A 41-year-old female
      presented for a right upper and middle lobe resection of a large neuroendocrine
      lung cancer. A brachial arterial line was inserted for continuous blood pressure
      monitoring using clinical landmarks. Six hours postoperatively the left hand was
      noted to be pale, cool and pulseless with complete paraesthesia. Thrombus was
      initially suspected on computed tomography angiography. Upon return to theatre,
      extensive dissection of the posterior brachial arterial wall was identified.
      CONCLUSION: We review our diagnostic pathway and treatment of this rare
      complication. Recommendations to minimise the risks of complications from
      brachial arterial line insertion are also overviewed. We recommend the routine
      utilization of ultrasound-guided technique and regular post-insertion
      neurovascular monitoring for the prevention and early recognition of
      complications from brachial artery catheter insertion.

PMID- 29329070
TI  - An alternative technique to use the Trachway(r) for nasotracheal intubation.

PMID- 29329071
TI  - Synthesis, anticancer activity and mechanism of action of new thiazole
      derivatives.
AB  - Thiazole derivatives are recognized to possess various biological activities as
      antiparasitic, antifungal, antimicrobial and antiproliferative. The present work
      reports the synthesis of 22 new substances belonging to two classes of compounds:
      thiosemicarbazones and thiazoles, with the purpose of developing new drugs that
      present high specificity for tumor cells and low toxicity to the organism. A
      cytotoxic screening was performed to evaluate the performance of the new
      derivatives in five tumor cell lines. Eight compounds were shown to be promising
      in at least three tumor cell lines. These compounds had their IC50 determined
      within 72 h and the activity structure ratio was assessed. The effect of the best
      compounds on PBMC and hemolytic activity assay was then evaluated. The compound
      1d was considered the most promising among the samples tested and its influence
      on cell cycle, DNA fragmentation and mitochondrial depolarization was evaluated.

PMID- 29329072
TI  - Development of potent and proteolytically stable human neuromedin U receptor
      agonists.
AB  - Neuromedin U (NMU) is a highly conserved endogenous peptide that is involved in a
      wide range of physiological processes such as regulation of feeding behavior, the
      stress response and nociception. The major limitation to use NMU as a therapeutic
      is its short half-life. Here, we describe the development of a set of novel NMU
      analogs based on NMU-8, by introducing unnatural amino acids into the native
      sequence. This approach shows that it is possible to generate molecules with
      increased potency and improved plasma stability without major changes of the
      peptidic nature or the introduction of large conjugates. When compared to the
      native NMU-8 peptide, compounds 16, 18 and 20 have potent agonist activity and
      affinity for both NMU receptors. Selectivity towards NMUR1 was observed when the
      Phe residue in position 4 was modified, whereas higher potencies at NMUR2 were
      found when substitutions of the Pro residue in position 6 were executed. To study
      the effect of the modifications on the proteolytic stability of the molecules, an
      in vitro stability assay in human plasma at 37  degrees C was performed. All
      analyzed analogs possessed an increased resistance against enzymatic degradation
      in human plasma resulting in half-lifes from 4 min for NMU-8, up to more than 23
      h for compound 42.

PMID- 29329073
TI  - Nanobiostructure of fibrous-like alumina functionalized with an analog of the
      BP100 peptide: Synthesis, characterization and biological applications.
AB  - The functionalization of alumina nanoparticles of specific morphology with
      antimicrobial peptides (AMP) can be a promising strategy for modeling medical
      devices and packaging materials for cosmetics, medicines or food, since the
      contamination by pathogens could be reduced. In this paper, we show the synthesis
      of a fibrous-like alumina nanobiostructure, as well as its functionalization with
      the peptide EAAA-BP100, an analog of the antimicrobial peptide BP100. The
      antibacterial activity of the obtained material against some bacterial strains is
      also investigated. The covalent binding of the peptide to the nanoparticles was
      promoted by a reaction between the carboxyl group of the glutamate side chain
      (E1) of the peptide and the amino groups of the alumina nanoparticles, previously
      modified by reaction with 3-aminopropyltrietoxysilane (APTES). The functionalized
      nanoparticles were characterized by zeta potential measurements, Fourier
      transform infrared spectroscopy, and other physicochemical techniques. Although
      the obtained alumina nanobiostructure shows a relatively low degree of
      substitution with EAAA-BP100, antibacterial activities against Escherichia coli
      and Salmonella typhimurium strains are appreciably higher than the activities of
      the free peptide. The obtained results can affect the design of new hybrid
      nanobiomaterials based on nanoparticles functionalized with AMP.

PMID- 29329074
TI  - Goat tendon collagen-human fibrin hydrogel for comprehensive parametric
      evaluation of HUVEC microtissue-based angiogenesis.
AB  - The cell and extracellular matrix (ECM) interactions play a very important role
      during angiogenesis. Remodeling of the extracellular matrix along with pro
      angiogenic/anti-angiogenic factors, and matrix-degrading proteases, accounts for
      endothelial cell growth, migration, and tube formation. However, for studying
      angiogenesis, only limited and expensive biomaterials are available. Despite
      being biocompatible, inexpensive, and easy availability; the potential of goat
      tendon collagen (GTC) has never been explored for vascular tissue engineering
      applications. Hence, the current investigation was focused on evaluating GTC as
      an alternative matrix for HUVEC microtissue-based angiogenesis. HUVEC
      microtissues (MTs), synthesized via hanging drop method, were subjected to
      angiogenesis in GTC-human fibrin (HF) hydrogels. Sprouting tip cells originated
      from the MTs within 24 h. Further, comprehensive in vitro study and in vivo
      validation revealed that, endothelial media with FBS and growth factors, 24 h old
      HUVEC MTs of 500 cells, seeded at 200 aggregates/cm3 in GTC-HF gel of 100 Pa
      elastic modulus, resulted in most optimal angiogenesis with intact lumen that was
      stable up to a week, without any supporting cells. Although early to predict, GTC
      HF matrix may serve as a potential ECM for engineering complex and functional
      tissues of clinical relevance.

PMID- 29329075
TI  - Anticoagulant polyurethane substrates modified with poly(2-methacryloyloxyethyl
      phosphorylcholine) via SI-RATRP.
AB  - A novel catalyst system of Reverse Atom Transfer Radical Polymerization (RATRP)
      to prepare Polyurethane (PU) films modified by poly(2-methacryloyloxyethyl
      phosphorylcholine) (pMPC) was studied in this article. In this system, PU film
      was pretreated by LaCl3/CA ethanol solution to obtain a hydrated surface allowing
      more initiators to be immobilized on it. Moreover, complexes composed of silane
      coupling agent 3-chloropropyltrimethoxysilane (CPTM), chlorhexidine acetate (CA)
      and lanthanum(III) worked as ligands of copper ions as a whole during RATRP
      process. PU films before and after modification were characterized by X-ray
      photoelectron spectroscopy (XPS) and static contact angle (SCA) to confirm that
      pMPC chains were successfully grafted from the substrates. Results of Plasma
      recalcification time assay, platelet adhesion test indicated excellent blood
      compatibility. Furthermore, the antibacterial activity of the material have been
      improved which proved by adhesion test of E.coil.

PMID- 29329077
TI  - Nano hydroxyapatite-blasted titanium surface creates a biointerface able to
      govern Src-dependent osteoblast metabolism as prerequisite to ECM remodeling.
AB  - Over the last several years, we have focused on the importance of intracellular
      signaling pathways in dynamically governing the biointerface between pre
      osteoblast and surface of biomaterial. Thus, this study investigates the
      molecular hallmarks involved in the pre-osteoblast relationship with different
      topography considering Machined (Mc), Dual Acid-Etching (DAE), and nano
      hydroxyapatite-blasted (nHA) groups. There was substantial differences in
      topography of titanium surface, considering Atomic Force Microscopy and water
      contact angle (Mc = 81.41 +/- 0.01; DAE = 97.18 +/- 0.01; nHA = 40.95 +/- 0.02).
      Later, to investigate their topography differences on biological responses, pre
      osteoblast was seeded on the different surfaces and biological samples were
      collected after 24 h (to consider adhesion signaling) and 10 days (to consider
      differentiation signaling). Preliminary results evidenced significant differences
      in morphological changes of pre-osteoblasts mainly resulting from the interaction
      with the DAE and nHA, distinguishing cellular adaptation. These results pushed us
      to analyze activation of specific genes by exploring qPCR technology. In
      sequence, we showed that Src performs crucial roles during cell adhesion and
      later differentiation of the pre-osteoblast in relationship with titanium-based
      biomaterials, as our results confirmed strong feedback of the Src activity on the
      integrin-based pathway, because integrin-beta1 (~5-fold changes), FAK (~12-fold
      changes), and Src (~3.5-fold changes) were significantly up-expressed when Src
      was chemically inhibited by PP1 (5 MUM). Moreover, ECM-related genes were
      rigorously reprogrammed in response to the different surfaces, resulting on
      Matrix Metalloproteinase (MMP) activities concomitant to a significant decrease
      of MMP inhibitors. In parallel, we showed PP1-based Src inhibition promotes a
      significant increase of MMP activity. Taking all our results into account, we
      showed for the first time nano hydroxyapatite-blasted titanium surface creates a
      biointerface able to govern Src-dependent osteoblast metabolism as pre-requisite
      to ECM remodeling.

PMID- 29329076
TI  - Attachment of nanoparticulate drug-release systems on poly(epsilon-caprolactone)
      nanofibers via a graftpolymer as interlayer.
AB  - Electrospun poly(epsilon-caprolactone) (PCL) fiber mats are modified using a
      chitosan grafted with PCL (CS-g-PCL), to improve the biological performance and
      to enable further modifications. The graft copolymer is immobilized by the
      crystallization of the PCL grafts on the PCL fiber surface as binding mechanism.
      In this way, the surface of the fibers is covered with chitosan bearing cationic
      amino groups, which allow adsorption of oppositely charged nanoparticulate drug
      delivery systems. The modification of the fiber mats and the attachment of the
      drug delivery systems are easy and scalable dip processes. The process is also
      versatile; it is possible to attach different polymeric and inorganic
      nanoparticulate drug-release systems of cationic or anionic nature. The
      modifications are verified using scanning electron microscopy (SEM) and confocal
      laser scanning microscopy (CLSM). As proof of principle, the release of
      ciprofloxacin from silica nanoparticles attached to the modified fiber mats is
      shown; however, the method is also suited for other biologically active
      substances including growth factors. The initial cellular attachment and
      proliferation as well as vitality of the cells is improved by the modification
      with CS-g-PCL and is further influenced by the type of the drug delivery system
      attached. Hence, this method can be used to transfer PCL fiber mats into
      bioactive implants for in-situ tissue engineering applications.

PMID- 29329078
TI  - Schmallenberg virus non-structural protein NSm: Intracellular distribution and
      role of non-hydrophobic domains.
AB  - Schmallenberg virus (SBV) induces fetal malformation, abortions and stillbirth in
      ruminants. While the non-structural protein NSs is a major virulence factor, the
      biological function of NSm, the second non-structural protein which consists of
      three hydrophobic transmembrane (I, III, V) and two non-hydrophobic regions (II,
      IV), is still unknown. Here, a series of NSm mutants displaying deletions of
      nearly the entire NSm or of the non-hydrophobic domains was generated and the
      intracellular distribution of NSm was assessed. SBV-NSm is dispensable for the
      generation of infectious virus and mutants lacking domains II - V showed growth
      properties similar to the wild-type virus. In addition, a comparable
      intracellular distribution of SBV-NSm was observed in mammalian cells infected
      with domain II mutants or wild-type virus. In both cases, NSm co-localized with
      the glycoprotein Gc in the Golgi compartment. However, domain IV-deletion mutants
      showed an altered distribution pattern and no co-localization of NSm and Gc.

PMID- 29329080
TI  - Intrauterine inflammatory activation, functional progesterone withdrawal, and the
      timing of term and preterm birth.
AB  - The central role of inflammatory processes in labour and delivery is now well
      recognised. However, the biomolecular, immunological and endocrine mechanisms
      involved in the labour process, and the clinical manifestations of inflammation
      in pregnancy, are complex, variable and modulated by factors such as aetiology,
      ethnicity and gestational age. In this review, evidence is presented of the
      pivotal relationship between progesterone and inflammation in pregnancy in terms
      of determining the timing of labour and delivery. The maternal inflammatory
      burden increases with advancing gestational age in response to endocrine,
      maturational, physical, metabolic and biochemical drivers, leading to functional
      progesterone withdrawal necessary for labour and delivery. Variability in the
      nature, timing and magnitude of these drivers influence the timing of delivery
      and the likelihood of preterm birth. Pathological inflammatory insults in
      pregnancy, such as infection, oxidative stress, senescence and maternal allograft
      rejection, can precipitate preterm birth, often involving common signalling
      pathways. Intrauterine infection is an important cause of early preterm birth,
      associated with delivery of the infants at greatest risk of death and disability;
      however, most preterm deliveries with intrauterine inflammatory activation are
      not infection-associated. This observation has important diagnostic and
      therapeutic implications and challenges. The key differences and similarities
      between infection-associated and sterile inflammation in this context are
      highlighted, and the clinical implications and significance of these processes
      and how they might be exploited are discussed.

PMID- 29329081
TI  - Presence of Fe-Al binary oxide adsorbent cake layer in ceramic membrane
      filtration and their impact for removal of HA and BSA.
AB  - To enhance the removal of natural organic matter (NOM) in ceramic (Ce) membrane
      filtration, an iron-aluminum binary oxide (FAO) was applied to the ceramic
      membrane surface as the adsorbent cake layer, and it was compared with heated
      aluminum oxide (HAO) for the evaluation of the control of NOM. Both the HAO and
      FAO adsorbent cake layers efficiently removed the NOM regardless of NOM's
      hydrophobic/hydrophilic characteristics, and the dissolved organic carbon (DOC)
      removal in NOM for FAO was 1-1.12 times greater than that for HAO, which means
      FAO was more efficient in the removal of DOC in NOM. FAO (0.03 MUm), which is
      smaller in size than HAO (0.4 MUm), had greater flux reduction than HAO. The flux
      reduction increased as the filtration proceeded because most of the organic
      foulants (colloid/particles and soluble NOM) were captured by the adsorbent cake
      layer, which caused fouling between the membrane surface and the adsorbent cake
      layer. However, no chemically irreversible fouling was observed on the Ce
      membrane at the end of the FAO adsorbent cake layer filtration. This means that a
      stable adsorbent cake layer by FAO formed on the Ce membrane, and that the
      reduced pure water flux of the Ce membrane, resulting from the NOM fouling, can
      easily be recovered through physicochemical cleaning.

PMID- 29329079
TI  - The interactome of EBV LMP1 evaluated by proximity-based BioID approach.
AB  - Epstein-Barr virus LMP1 is an oncoprotein required for immortalizing B
      lymphocytes and also plays important roles in transforming non-lymphoid tissue.
      The discovery of LMP1 protein interactions will likely generate targets to treat
      EBV-associated cancers. Here, we define the broader LMP1 interactome using the
      recently developed BioID method. Combined with mass spectrometry, we identified
      over 1000 proteins across seven independent experiments with direct or indirect
      relationships to LMP1. Pathway analysis suggests that a significant number of the
      proteins identified are involved in signal transduction and protein or vesicle
      trafficking. Interestingly, a large number of proteins thought to be important in
      the formation of exosomes and protein targeting were recognized as probable LMP1
      interacting partners, including CD63, syntenin-1, ALIX, TSG101, HRS, CHMPs, and
      sorting nexins. Therefore, it is likely that LMP1 modifies protein trafficking
      and exosome biogenesis pathways. In support of this, knock-down of syntenin-1 and
      ALIX resulted in reduced exosomal LMP1.

PMID- 29329082
TI  - The domestic fowl (Gallus gallus domesticus) embryo as an alternative for
      mammalian experiments - Validation of a test method for the detection of
      endocrine disrupting chemicals.
AB  - In recent decades the embryo of Gallus g. domesticus has been widely used as a
      model for the study of early sexual development and the potential impact of
      substances affecting development, including endocrine disrupting chemicals
      (EDCs). Since there is no standardized procedure available for experiments with
      the chicken embryo, the objective of our project is to expedite the protocol to
      assess the potential effects of EDCs on early sexual differentiation. The main
      aim of the present study was to systematically investigate the natural
      variability of individual developmental and histological key parameters in
      untreated and solvent-treated control groups, since this has been insufficiently
      addressed so far. A further aim was to provide robust values for all parameters
      investigated in control and substance experiments, using two known estrogenic
      compounds, bisphenol A (75/150/300 MUg/g egg) and 17alpha-ethinylestradiol (20
      ng/g egg). On embryonic day 1 eggs were injected with the estrogenic compounds.
      On embryonic day 19 histological gonadal data as well as morphological parameters
      were noted. In baseline experiments with control groups the selected endpoints
      showed reproducible results with low variabilities. Furthermore, gonadal
      endpoints responded sensitively to the treatment with the two model EDCs. Thus,
      these endpoints are recommended for the assessment of suspected EDCs in which the
      values provided for all parameters can serve as validity criteria in future
      experiments. The embryo of G. domesticus has shown to be a suitable alternative
      to currently accepted mammalian bioassays for the impact assessment of EDCs on
      reproductive tissues.

PMID- 29329083
TI  - A label-free electrochemical system for comprehensive monitoring of o
      chlorophenol.
AB  - o-Chlorophenol (OCP) is a priority pollutant that poses serious health threats to
      the public. The following study designs a simple electrochemical system to
      monitor the concentration and toxicity of OCP. This system was primarily
      characterized by the integration of both physicochemical and biological
      monitoring procedures that had a synergistic effect between the functionalized
      carbon nanotubes and rhodamine B. This resulted in excellent electrocatalytic
      activities toward OCP and cellular purine bases. The peak current of OCP was
      linear with concentrations ranging from 0.05-125.0 MUM and the detection limit
      was 0.028 MUM under optimal testing conditions. There was an enhanced
      voltammetric signal detected that was caused by the guanine/xanthine of human
      hepatoma (HepG2) cells. The cytotoxicity of OCP to HepG2 cells was assessed using
      the proposed system. The obtained IC50 value was 512.86 MUM. This study provided
      a fast, label-free, and low-cost platform for the comprehensive assessment of
      OCP. This is highly beneficial for simplifying the environmental monitoring
      process.

PMID- 29329085
TI  - An integrated approach to assess the impacts of zinc pyrithione at different
      levels of biological organization in marine mussels.
AB  - The mechanisms of sublethal toxicity of the antifouling biocide, zinc pyrithione
      (ZnPT), have not been well-studied. This investigation demonstrates that 14-d
      sublethal exposure to ZnPT (0.2 or 2 MUM, alongside inorganic Zn and sea water
      controls) is genotoxic to mussel haemocytes but suggests that this is not caused
      by oxidative DNA damage as no significant induction of oxidised purines was
      detected by Fpg-modified comet assay. More ecologically relevant endpoints,
      including decreased clearance rate (CR), cessation of attachment and decreased
      tolerance of stress on stress (SoS), also showed significant response to ZnPT
      exposure. Our integrated approach was underpinned by molecular analyses (qRT-PCR
      of stress-related genes, 2D gel electrophoresis of proteins) that indicated ZnPT
      causes a decrease in phosphoenolpyruvate carboxykinase (PEPCK) expression in
      mussel digestive glands, and that metallothionein genes are upregulated; PEPCK
      downregulation suggests that altered energy metabolism may also be related to the
      effects of ZnPT. Significant relationships were found between % tail DNA (comet
      assay) and all higher level responses (CR, attachment, SoS) in addition to PEPCK
      expression. Principal component analyses suggested that expression of selected
      genes described more variability within groups whereas % tail DNA reflected
      different ZnPT concentrations.

PMID- 29329084
TI  - Sources of polychlorinated dibenzo-p-dioxins and dibenzofurans, and biphenyls in
      Chinese mitten crabs.
AB  - Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and polychlorinated
      biphenyls (PCBs) in Chinese mitten crabs from several areas were determined. The
      toxic equivalents (TEQs) for the mean PCDD/F and total PCDD/F and dioxin-like
      PCBs were 2.9 +/- 2.7 and 5.7 +/- 4.0 pg TEQ g-1, respectively. The mean
      concentrations of PCBs and dl-PCBs were 282 and 59 times the concentrations of
      PCDD/Fs, respectively. PCDD/F and PCB sources in the crab food web were assessed.
      The total TEQ of PCDD/F and PCB supplied by crab compound feed was 2.1 times the
      TEQ in crab meat. Broken corn, aquatic biota, and water contributed around 12% of
      the total TEQ inputs for crab meat. The contribution from sediment was around 164
      times that from crab meat, and sediment may be the most important source of
      PCDD/Fs and PCBs in cultured crabs. Principal component analysis (PCA) and stable
      isotope ratios for nitrogen (delta15N) and carbon (delta13C) supported the TEQ
      results. The mean total PCDD/F and dl-PCB TEQ exposure for humans consuming crabs
      was 3.4 pg TEQ per kilogram of body weight per day. The PCDD/Fs and PCBs in >80%
      of the crab samples would not cause the tolerable daily intake to be exceeded.

PMID- 29329086
TI  - Effect of exogenous phosphate on the lability and phytoavailability of arsenic in
      soils.
AB  - The effect of exogenous phosphate (P, 200 mg?kg-1 soil) on the lability and
      phytoavailability of arsenic (As) was studied using the diffusive gradients in
      thin films (DGT) technique. Lettuce were grown on the As-amended soils following
      the stabilization of soil labile As after 90 days incubation. Phosphate (P)
      application generally facilitated plant growth except one grown on P-sufficient
      soil. Soil labile As concentration increased in all the soils after P application
      due to a competition effect. Plant As concentration increased in red soils
      collected from Hunan Province, while decreases were observed in the other soils.
      Even though, an overall trend of decrease was obtained in As phytoavailability
      along with the increase of DGT-measured soil labile P/As molar ratio. The
      functional equation between P/As and As phytoavailability provided a critical
      value of 1.7, which could be used as a guidance for rational P fertilization,
      thus avoiding overfertilization.

PMID- 29329087
TI  - Occurrence of perfluoroalkyl substances (PFAS) in garden produce at homes with a
      history of PFAS-contaminated drinking water.
AB  - The decades-long disposal of manufacturing waste containing perfluoroalkyl
      substances (PFAS) in landfills resulted in contamination of groundwater serving
      as the drinking water supply for the eastern Twin Cities metropolitan region.
      While measures were taken to reduce the levels of PFAS in the drinking water,
      questions remained about possible non-drinking water pathways of exposure in
      these communities. The Minnesota Department of Health (MDH) investigated whether
      PFAS in water used for yard and garden irrigation results in elevated
      concentrations of PFAS in soil and home-grown produce. In 2010, samples of
      outdoor tap water, garden soil, and garden produce were collected at homes
      impacted by the contamination and analyzed for several PFAS. Perfluorobutanoic
      acid (PFBA) was the primary PFAS present in water, followed by perfluoropentanoic
      acid (PFPeA). Although PFBA, perfluorooctanoic acid (PFOA) and perfluorooctane
      sulfonate (PFOS) were present in 100% of soil samples at higher concentrations
      compared to other PFAS, only PFBA was readily translocated to plants. Significant
      determinants of PFBA concentration in produce were the amount of PFBA applied to
      the garden via watering and the type of produce tested. Results from this real
      world study are consistent with experimental findings that short-chain PFAS have
      the highest potential to translocate to and bioaccumulate in edible plants. These
      findings are globally relevant, as short-chain PFAS serve as commercial
      substitutes for longer-chain compounds and are increasingly detected in water due
      to their relatively high solubility and mobility.

PMID- 29329088
TI  - Metal sorption to Spodosol Bs horizons: Organic matter complexes predominate.
AB  - While metal sorption mechanisms have been studied extensively for soil surface
      horizons, little information exists for subsoils, for example Spodosol Bs
      horizons. Here the sorption of cadmium(II), copper(II) and lead(II) to seven Bs
      horizons from five sites was studied. Extended X-ray absorption fine structure
      (EXAFS) spectroscopy showed that cadmium(II) and lead(II) were bound as inner
      sphere complexes to organic matter. Addition of o-phosphate (to 1 MUmol l-1) did
      not result in any significant enhancement of metal sorption, nor did it influence
      EXAFS speciation. An assemblage model using the SHM and CD-MUSIC models
      overestimated metal sorption for six out of seven soil samples. To agree with
      experimental results, substantial decreases (up to 8-fold) had to be made for the
      fraction 'active organic matter', fHS, while the point-of-zero charge (PZC) of
      ferrihydrite had to be increased. The largest decreases of fHS were found for the
      soils with the lowest ratio of pyrophosphate-to oxalate-extractable Al
      (Alpyp/Alox), suggesting that in these soils, humic and fulvic acids were to a
      large extent inaccessible for metal sorption. The low reactivity of ferrihydrite
      towards lead(II) can be explained by potential spillover effects from co-existing
      allophane, but other factors such as ferrihydrite crystallisation could not be
      ruled out. In conclusion, organic matter was the predominant sorbent for
      cadmium(II), copper(II) and lead(II). However, for lead(II) the optimised model
      suggests additional, but minor, contributions from Fe (hydr)oxide surface
      complexes. These results will be important to correctly model metal sorption in
      spodic materials.

PMID- 29329089
TI  - Neural circuit dysfunction in mouse models of neurodevelopmental disorders.
AB  - Neuropsychiatric disorders arise from the alteration of normal brain
      developmental trajectories disrupting the function of specific neuronal circuits.
      Recent advances in human genetics have greatly accelerated the identification of
      genes whose variation increases the susceptibility for neurodevelopmental
      disorders, most notably for autism spectrum disorder (ASD) and schizophrenia. In
      parallel, experimental studies in animal models-most typically in mice-are
      beginning to shed light on the role of these genes in the development and
      function of specific brain circuits. In spite of their limitations, understanding
      the impact of pathological gene variation in animal models at the level of
      specific neuronal populations and circuits will likely contribute to orienting
      human clinical studies in the search for precise disease mechanisms and novel
      treatments.

PMID- 29329090
TI  - Simultaneous accelerated solvent extraction and hydrolysis of 11-nor-Delta9
      tetrahydrocannabinol-9-carboxylic acid glucuronide in meconium samples for gas
      chromatography-mass spectrometry analysis.
AB  - Cannabis misuse during pregnancy is associated with severe impacts on the mother
      and baby health, such as newborn low birth weight, growth restriction, pre-term
      birth, neurobehavioral and developmental deficits. In most of the cases, drug
      abuse is omitted or denied by the mothers. Thus, toxicological analyzes using
      maternal-fetal matrices takes place as a suitable tool to assess drug use.
      Herein, meconium was the chosen matrix to evaluate cannabis exposure through
      identification and quantification of 11-nor-Delta9-tetrahydrocannabinol-9
      carboxylic (THCCOOH). Accelerated solvent extraction (ASE) was applied for sample
      preparation technique to simultaneously extract and hydrolyze conjugated THCCOOH
      from meconium, followed by a solid-phase extraction (SPE) procedure. The method
      was developed and validated for gas chromatography-mass spectrometry (GC-MS),
      reaching hydrolysis efficiency of 98%. Limits of detection (LOD) and
      quantification (LOQ) were, respectively, 5 and 10 ng/g. The range of linearity
      was LOQ to 500 ng/g. Inter and intra-batch coefficients of variation were <8.4%
      for all concentration levels. Accuracy was in 101.7-108.9% range. Recovery was on
      average 60.3%. Carryover effect was not observed. The procedure was applied in
      six meconium samples from babies whose mothers were drug users and showed
      satisfactory performance to confirm fetal cannabis exposure.

PMID- 29329091
TI  - Determination of IMM-H004 and its active glucuronide metabolite in rat plasma and
      Ringer's solution by ultra-performance liquid chromatography-tandem mass
      spectrometry.
AB  - IMM-H004 is a novel neuroprotective agent and its glucuronide metabolite IMM
      H004G has similar protective effects against cerebral ischemic injury in vivo and
      in vitro. A specific and sensitive ultra-performance liquid chromatography-tandem
      mass spectrometry method was established and validated for determination of IMM
      H004 and IMM-H004G simultaneously in rat plasma and Ringer's solution. Plasma
      samples containing IMM-H004, IMM-H004G and internal standard propranolol were
      prepared by direct protein precipitation in a sample-to-solvent ratio of 1:2:6
      (plasma: water: acetonitrile), whereas no protein precipitation was required for
      Ringer's solution samples. Separation was performed with a gradient mobile phase
      of methanol/water with 0.5% formic acid (v/v) on Eclipse Plus C18 column
      (2.1*50mm, 3.5MUm) at a flow rate of 0.3mL/min. The detection was operated on a
      triple quadrupole mass spectrometer in positive ion multiple reaction monitoring
      (MRM) mode. The monitored transitions were 305.1->248.1 for IMM-H004, 481.3
      >305.1 for IMM-H004G and 260.1->183.1 for propranolol. The linear ranges of IMM
      H004 and IMM-H004G were 5 to 3000ng/mL and 10 to 3000ng/mL for plasma method and
      0.5 to 500ng/mL for Ringer's solution method. All the intra-day and inter-day
      precision and accuracy for the two analytes in rat plasma were below 7.5% and the
      intra-day precision and accuracy for analytes in Ringer's solution were within +/
      14.7%. There was no obvious matrix effect and the recoveries of the analytes were
      higher than 94.2%. IMM-H004 and IMM-H004G were stable during one analytic
      process. The established method was applied successfully to plasma
      pharmacokinetic and brain microdialysis studies of IMM-H004 and IMM-H004G in rats
      after a single intravenous administration of IMM-H004.

PMID- 29329092
TI  - Effect of aspirin on the pharmacokinetics and absorption of panax notoginseng
      saponins.
AB  - BACKGROUND: Panax notoginseng saponins, a traditional Chinese medicine
      extraction, and aspirin are both widely used to treat cerebral infarction in
      China. Good results in clinical practice have been achieved, when Panax
      notoginseng saponins was taken together with aspirin. METHODS: To investigate the
      interaction of the two drugs in vivo, the concentration of notoginsenoside R1,
      ginsenoside Rg1, Rb1, Re and Rd. in blood were simultaneously measured by
      UPLC/MS/MS. Sample preparation was carried out by the protein precipitation
      technique with an internal standard saikosaponin A standard. The separation of
      six components was achieved by using an ACQUITY UPLC (r)BEH C18 column (1.7MUm
      2.1*100mm) by gradient elution using water (containing 0.2% formic acid) and
      acetonitrile (containing 0.2% formic acid) as the mobile phase at a flow rate of
      0.2mL/min. The pharmacokinetic parameters were determined using non-compartmental
      analysis. The transport of notoginsenoside R1, ginsenoside Rg1, Rb1, Re and Rd.
      in MDCK -MDR1 cell monolayer was also used to verify the conclusion of
      pharmacokinetic drug-drug interaction and study the mechanism of drug
      interaction. RESULTS: The concentrations of the five components increased in a
      certain extent when the two drugs administered together in rats. The values of
      apparent permeability coefficients were significantly increased when the two
      drugs were used together. Aspirin and salicylic acid could destroy the tight
      junction protein and open the intercellular space to increase the absorption of
      Panax notoginseng saponins. CONCLUSION: Pharmacokinetic drug-drug interaction in
      vivo existed between Panax notoginseng saponins and aspirin. The drug-drug
      interaction mainly occurred in the process of absorption.

PMID- 29329093
TI  - Size exclusion chromatography (SEC-HPLC) as an alternative to study thrombin
      inhibition.
AB  - In vitro analysis of anticoagulant compounds with a potential use as
      antithrombotic drugs, has been traditionally performed using techniques like
      spectrophotometry, turbidimetry, as well as electrochemical and clinical assays.
      Although, these techniques have some disadvantages such as: the inability to
      measure the total biological activity of thrombin, interferences and, sometimes,
      the quantitative determination of the inhibition ratio is not accurate. In the
      present work, the conversion of fibrinogen to fibrin was monitored by molecular
      exclusion chromatography (SEC-HPLC) in three different reaction systems. An
      inhibition percentage of 43.19+/-2.02% was obtained using heparin as an
      anticoagulant, in addition to the determination of the percentage of heparin
      bonded to thrombin. This methodology has not been previously described and has
      high potential for the determination of anticoagulant capacity with higher
      precision, the determination of thrombin's total biological activity and the
      quantitative determination of the inhibition ratio.

PMID- 29329094
TI  - Hydrophilic interaction liquid chromatography in the speciation analysis of
      selenium.
AB  - The hydrophilic interaction liquid chromatography (HILIC) coupled to mass
      spectrometry was employed to study retention behavior of selected selenium
      compounds using two different HILIC stationary phases: silica and zwitterionic.
      Two organic solvents - acetonitrile and methanol - were compared as a component
      of mobile phase. Separation parameters such as a content of organic modifier, the
      eluent pH and inorganic buffer concentration were investigated. Based on all
      observations, methanol seems to be beneficial for the separation of studied
      compounds. The optimal HILIC separation method involved silica column and eluent
      composed of 85% MeOH and CH3COONH4 (8 mM, pH 7) was compared to RP method in
      terms of time of the single run, the separation efficiency and limit of
      detection.

PMID- 29329095
TI  - Investigation of silver (Ag) deposition in tissues from stranded cetaceans by
      autometallography (AMG).
AB  - Silver, such as silver nanoparticles (AgNPs), has been widely used in commercial
      products and may be released into the environment. The interaction between Ag
      deposition and biological systems is raising serious concerns because of one
      health consideration. Cetaceans, as the top predators of the oceans, may be
      exposed to Ag/Ag compounds and suffer negative health impacts from the deposition
      of these compounds in their bodies. In the present study, we utilized
      autometallography (AMG) to localize the Ag in the liver and kidney tissues of
      cetaceans and developed a model called the cetacean histological Ag assay (CHAA)
      to estimate the Ag concentrations in the liver and kidney tissues of cetaceans.
      Our results revealed that Ag was mainly located in hepatocytes, Kupffer cells and
      the epithelial cells of some proximal renal tubules. The tissue pattern of Ag/Ag
      compounds deposition in cetaceans was different from those in previous studies
      conducted on laboratory rats. This difference may suggest that cetaceans have a
      different metabolic profile of Ag, so a presumptive metabolic pathway of Ag in
      cetaceans is advanced. Furthermore, our results suggest that the Ag contamination
      in cetaceans living in the North-western Pacific Ocean is more severe than that
      in cetaceans living in other marine regions of the world. The level of Ag
      deposition in cetaceans living in the former area may have caused negative
      impacts on their health condition. Further investigations are warranted to study
      the systemic Ag distribution, the cause of death/stranding, and the infectious
      diseases in stranded cetaceans with different Ag concentrations for
      comprehensively evaluating the negative health effects caused by Ag in cetaceans.

PMID- 29329096
TI  - Water contamination by endocrine disruptors: Impacts, microbiological aspects and
      trends for environmental protection.
AB  - Hormone active agents constitute a dangerous class of pollutants. Among them,
      those agents that mimic the action of estrogens on target cells and are part of
      the group of endocrine-disruptor compounds (EDCs) are termed estrogenic EDCs, the
      main focus of this review. Exposure to these compounds causes a number of
      negative effects, including breast cancer, infertility and animal
      hermaphroditism. However, especially in underdeveloped countries, limited efforts
      have been made to warn people about this serious issue, explain the methods of
      minimizing exposure, and develop feasible and efficient mitigation strategies at
      different levels and in various environments. For instance, the use of
      bioremediation processes capable of transforming EDCs into environmentally
      friendly compounds has been little explored. A wide diversity of estrogen
      degrading microorganisms could be used to develop such technologies, which
      include bioremediation processes for EDCs that could be implemented in biological
      filters for the post-treatment of wastewater effluent. This review describes
      problems associated with EDCs, primarily estrogenic EDCs, including exposure as
      well as the present status of understanding and the effects of natural and
      synthetic hormones and estrogenic EDCs on living organisms. We also describe
      potential biotechnological strategies for EDC biodegradation, and suggest novel
      treatment approaches for minimizing the persistence of EDCs in the environment.

PMID- 29329097
TI  - Sources and transformation pathways for dichlorodiphenyltrichloroethane (DDT) and
      metabolites in soils from Northwest Fujian, China.
AB  - Dicofol (2,2,2-trichloro-1,1-bis-(p-chlorophenyl)ethanol) found in the
      environment is not only a miticide originated from commercial use, but also a
      metabolite of dichlorodiphenyltrichloroethane (DDT), which is often overlooked.
      To verify the sources and transformation pathways of DDT and related metabolites
      in soils, we measured p,p'-(dicofol + DBP) (sum of p,p'-dicofol and 4,4'
      dichlorobenzophenone), DDT and six metabolites in soils from Northwest Fujian,
      China. The ratios of 1,1,1-trichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl)ethane
      (o,p'-DDT)/1,1,1-trichloro-2,2-bis-(p-chlorophenyl)ethane (p,p'-DDT) and the mass
      balance demonstrated that p,p'-(dicofol + DBP) predominantly originated from p,p'
      DDT transformation rather than from actual dicofol application. p,p'-(dicofol +
      DBP) accounted for 45.0% as the primary metabolites of DDT in this study, more
      than 1,1-dichloro-2,2-bis-(p-chlorophenyl)ethylene (p,p'-DDE) and 1,1-dichloro
      2,2-bis-(p-chlorophenyl)ethane (p,p'-DDD), which might lead to large
      overestimations of the fresh DDT input by using the traditional ratio of (?2DDD +
      ?2DDE)/?2DDT (with all o,p'- and p,p'- isomers included). In paddy fields where
      the conditions alternate between aerobic (dry period) and anaerobic (wet period),
      both p,p'-DDD and p,p'-DDE were likely to degrade to 1-chloro-2,2-bis-(p
      chlorophenyl)ethylene (p,p'-DDMU), which further transformed to 2,2-bis(p
      chlorophenyl)ethylene (p,p'-DDNU). Degradation of p,p'-DDMU to p,p'-DDNU mainly
      occurred in waterlogged paddy soils. However, p,p'-DDNU might not transform to
      other higher-order metabolites in aerobic surface soils. Overall, our study
      confirmed p,p'-(dicofol + DBP) as metabolites of p,p'-DDT, suggested DDE and DDD
      were parallel precursors of DDMU, and further verified the transformation
      pathways of DDT in surface soils.

PMID- 29329098
TI  - Effect of organic amendments on cadmium stress to pea: A multivariate comparison
      of germinating vs young seedlings and younger vs older leaves.
AB  - Despite significant recent advancement in research, biogeochemical behavior of
      heavy metals with respect to their applied form is still topical. Moreover, metal
      toxicity to plants may vary with their stage of development/maturity. Therefore,
      this study for the first time evaluated the influence of
      ethylenediaminetetraacetic acid (EDTA) and citric acid (CA) on cadmium (Cd)
      accumulation and toxicity to germinating and young pea seedlings as well as in
      younger and older leaves. The experimental setup of current study consisted of
      two separate studies. The first study was performed on germinating seedlings
      grown in a Cd-contaminated sand media. Pea seeds were treated with two levels of
      Cd (Cd-25 and Cd-100) alone and combined with different levels of EDTA and CA.
      The second study was carried out in hydroponic solution. The influence of organic
      amendments on Cd accumulation and toxicity to pea plants was evaluated by
      determining Cd contents in pea seedlings, H2O2 contents, chlorophyll contents and
      lipid peroxidation in younger and older leaves. Cadmium stress caused
      overproduction of H2O2 in roots and leaves of pea seedlings. Cadmium-induced
      overproduction of H2O2 caused a decrease in the pigment contents and increased
      lipid peroxidation. Application of EDTA at higher levels (81 and 200uM) increased
      Cd accumulation by pea plants. However, CA did not affect Cd accumulation by pea.
      Both EDTA and CA increased Cd-induced H2O2 production and lipid peroxidation.
      Younger pea leaves showed more sensitivity to Cd stress compared to older leaves.
      Similarly, Cd toxicity was more pronounced in germinating seedlings than young
      seedlings. Moreover, Pearson correlation and principal component analysis (PCA)
      showed very interesting correlations between treatments and stress responses of
      germination and young seedlings as well as younger and older leaves. Based on
      multivariate analysis, it is proposed that the Cd toxicity to pea plants greatly
      vary with its growth stage and the maturity of organs (younger or older leaves).

PMID- 29329099
TI  - Accumulation patterns and risk assessment of metals and metalloid in muscle and
      offal of free-range chickens, cattle and goat in Benin City, Nigeria.
AB  - The use of free range animals for monitoring environmental health offers
      opportunities to detect exposure and assess the toxicological effects of
      pollutants in terrestrial ecosystems. Potential human health risk of dietary
      intake of metals and metalloid via consumption of offal and muscle of free range
      chicken, cattle and goats by the urban population in Benin City was evaluated.
      Muscle, gizzard, liver and kidney samples were analyzed for Cr, Mn, Fe, Co, Ni,
      Cu, Zn, As, Cd, and Pb concentrations using inductively coupled plasma mass
      spectrometer (ICP-MS) while Hg was determined using Hg analyzer. Mean
      concentrations of metals (mg/kg ww) varied significantly depending upon the
      tissues and animal species. Human health risk estimations for children and adults
      showed estimated daily intake (EDI) values of tissues below oral reference dose
      (RfD) threshold for non essential metals Cd, As, Pb and Hg thus strongly
      indicating no possible health risk via consumption of animal based food.
      Calculated Hazard quotient (THQ) was less than 1 (< 1) for all the metals
      analyzed for both adult and children. However, Cd and As had the highest value of
      THQ suggestive of possible health risk associated with continuous consumption of
      Cd and As contaminated animal based foods. Hazard Index (HI) for additive effect
      of metals was higher in chicken liver and gizzard for children and chicken liver
      for adults. Thus, HI indicated that chicken liver and gizzard may contribute
      significantly to adult and children dietary exposure to heavy metals. Principal
      component analysis (PCA) showed a clear species difference in metal accumulation
      between chickens and the ruminants. This study provides baseline data for future
      studies and also valuable evidence of anthropogenic impacts necessary to initiate
      national and international policies for control of heavy metal and metalloid
      content in food items.

PMID- 29329100
TI  - A Web-Based System for Bayesian Benchmark Dose Estimation.
AB  - BACKGROUND: Benchmark dose (BMD) modeling is an important step in human health
      risk assessment and is used as the default approach to identify the point of
      departure for risk assessment. A probabilistic framework for dose-response
      assessment has been proposed and advocated by various institutions and
      organizations; therefore, a reliable tool is needed to provide distributional
      estimates for BMD and other important quantities in dose-response assessment.
      OBJECTIVES: We developed an online system for Bayesian BMD (BBMD) estimation and
      compared results from this software with U.S. Environmental Protection Agency's
      (EPA's) Benchmark Dose Software (BMDS). METHODS: The system is built on a
      Bayesian framework featuring the application of Markov chain Monte Carlo (MCMC)
      sampling for model parameter estimation and BMD calculation, which makes the BBMD
      system fundamentally different from the currently prevailing BMD software
      packages. In addition to estimating the traditional BMDs for dichotomous and
      continuous data, the developed system is also capable of computing model-averaged
      BMD estimates. RESULTS: A total of 518 dichotomous and 108 continuous data sets
      extracted from the U.S. EPA's Integrated Risk Information System (IRIS) database
      (and similar databases) were used as testing data to compare the estimates from
      the BBMD and BMDS programs. The results suggest that the BBMD system may
      outperform the BMDS program in a number of aspects, including fewer failed BMD
      and BMDL calculations and estimates. CONCLUSIONS: The BBMD system is a useful
      alternative tool for estimating BMD with additional functionalities for BMD
      analysis based on most recent research. Most importantly, the BBMD has the
      potential to incorporate prior information to make dose-response modeling more
      reliable and can provide distributional estimates for important quantities in
      dose-response assessment, which greatly facilitates the current trend for
      probabilistic risk assessment. https://doi.org/10.1289/EHP1289.

PMID- 29329101
TI  - Spatial Variation of Endotoxin Concentrations Measured in Ambient PM10 in a
      Livestock-Dense Area: Implementation of a Land-Use Regression Approach.
AB  - BACKGROUND: Results from studies on residential health effects of livestock
      farming are inconsistent, potentially due to simple exposure proxies used (e.g.,
      livestock density). Accuracy of these proxies compared with measured exposure
      concentrations is unknown. OBJECTIVES: We aimed to assess spatial variation of
      endotoxin in PM10 (particulate matter <=10MUm) at residential level in a
      livestock-dense area, compare simple livestock exposure proxies to measured
      endotoxin concentrations, and evaluate whether land-use regression (LUR) can be
      used to explain spatial variation of endotoxin. METHODS: The study area (3,000
      km2) was located in Netherlands. Ambient PM10 was collected at 61 residential
      sites representing a variety of surrounding livestock-related characteristics.
      Three to four 2-wk averaged samples were collected at each site. A local
      reference site was used for temporal variation adjustment. Samples were analyzed
      for PM10 mass by weighing and for endotoxin by using the limulus amebocyte lysate
      assay. Three LUR models were developed, first a model based on general livestock
      related GIS predictors only, followed by models that also considered species
      specific predictors and farm type-specific predictors. RESULTS: Variation in
      concentrations measured between sites was substantial for endotoxin and more
      limited for PM10 (coefficient of variation: 43%, 8%, respectively); spatial
      patterns differed considerably. Simple exposure proxies were associated with
      endotoxin concentrations although spatial variation explained was modest
      (R2<26%). LUR models using a combination of animal-specific livestock-related
      characteristics performed markedly better, with up to 64% explained spatial
      variation. CONCLUSION: The considerable spatial variation of ambient endotoxin
      concentrations measured in a livestock-dense area can largely be explained by LUR
      modeling based on livestock-related characteristics. Application of endotoxin LUR
      models seems promising for residential exposure estimation within health studies.
      https://doi.org/10.1289/EHP2252.

PMID- 29329103
TI  - Analysis of anti-ganglioside antibodies by a line immunoassay in patients with
      chronic-inflammatory demyelinating polyneuropathies (CIDP).
AB  - BACKGROUND: Unlike for acute immune-mediated neuropathies (IN), anti-ganglioside
      autoantibody (aGAAb) testing has been recommended for only a minority of chronic
      IN yet. Thus, we used a multiplex semi-quantitative line immunoassay (LIA) to
      search for aGAAb in chronic-inflammatory demyelinating polyneuropathy (CIDP) and
      its clinical variants. METHODS: Anti-GAAb to 11 gangliosides and sulfatide (SF)
      were investigated by LIA in 61 patients with IN (27 typical CIDP, 12 distal
      acquired demyelinating polyneuropathy, 6 multifocal-acquired demyelinating
      sensory/motor polyneuropathy, 10 sensory CIDP, 1 focal CIDP and 5 multifocal
      motoric neuropathy), 40 with other neuromuscular disorders (OND) (15 non-immune
      polyneuropathies, 25 myasthenia gravis), 29 with multiple sclerosis (MS) and 54
      healthy controls (HC). RESULTS: In contrast to IgG, positive anti-GAAB IgM
      against at least one ganglioside/SF was found in 17/61 (27.9%) IN compared to
      2/40 (5%) in OND, 2/29 MS (6.9%) and 4/54 (7.4%) in HC (p=0.001). There was a
      statistically higher prevalence of anti-sulfatide (aSF) IgM in IN compared to OND
      (p=0.008). Further, aGM1 IgM was more prevalent in IN compared to OND and HC
      (p=0.009) as well as GD1b in IN compared to HC (p<0.04). The prevalence of aGM1
      IgM in CIDP was lower compared to in multifocal motor neuropathy (MMN) (12% vs.
      60%, p=0.027). Patients showing aSF, aGM1 and aGM2 IgM were younger compared to
      aGAAb negatives (p<0.05). Patients with aSF IgM positivity presented more
      frequently typical CIDP and MMN phenotypes (p<0.05, respectively). CONCLUSIONS:
      The aGAAb LIA revealed an elevated frequency of at least one aGAAb IgM in
      CIDP/MMN patients. Anti-SF, aGM1 and aGM2 IgM were associated with younger age
      and anti-SF with IN phenotypes.

PMID- 29329104
TI  - Contraception usage among young adult men of a Nigerian university.
AB  - Background Family planning services recognize reproductive health as the joint
      responsibility of both men and women. Efforts need to be shifted to men's own
      sexual health in order to achieve the Millennium Development Goals (MDGs) for
      reduction of maternal mortality and HIV transmission. Aims To determine the
      methods of contraception used by young adult men and factors that influence their
      choice of contraceptive. Methodology A cross-sectional descriptive study was done
      using structured questionnaires to extract relevant information from consented
      young male adult between ages of 16 and 24 years of Ladoke Akintola University of
      Technology (LAUTECH), Ogbomoso, Nigeria. Data was coded using Microsoft Excel and
      was analyzed using the SPSS version 17. Results The majority of the respondents
      212 (71.6%) had had sexual intercourse. Mean age at first sexual debut was 17.8
      +/- 2.5 years. The majority of the respondents 124 (58.5%) did not use any
      contraceptives during their first sexual experience and over 1/5th (21.2%) of
      respondents had impregnated a partner in the past with the majority, 39 (86.7%)
      of such pregnancies resulting in an induced abortion. Frequency of religious
      services attendance showed a statistically significant difference with
      respondents that were sexually active or had previous sex (p < 0.001). Conclusion
      Male involvement and education about contraceptive methods, use and consistency
      of contraception could have a drastic reduction in unwanted pregnancies and also
      a reduction in abortion complications.

PMID- 29329102
TI  - Arsenic Exposure from Drinking Water and Urinary Metabolomics: Associations and
      Long-Term Reproducibility in Bangladesh Adults.
AB  - BACKGROUND: Chronic exposure to inorganic arsenic from drinking water has been
      associated with a host of cancer and noncancer diseases. The application of
      metabolomics in epidemiologic studies may allow researchers to identify
      biomarkers associated with arsenic exposure and its health effects. OBJECTIVE:
      Our goal was to evaluate the long-term reproducibility of urinary metabolites and
      associations between reproducible metabolites and arsenic exposure. METHODS: We
      studied samples and data from 112 nonsmoking participants (58 men and 54 women)
      who were free of any major chronic diseases and who were enrolled in the Health
      Effects of Arsenic Longitudinal Study (HEALS), a large prospective cohort study
      in Bangladesh. Using a global gas chromatography-mass spectrometry platform, we
      measured metabolites in their urine samples, which were collected at baseline and
      again 2 y apart, and estimated intraclass correlation coefficients (ICCs). Linear
      regression was used to assess the association between arsenic exposure at
      baseline and metabolite levels in baseline urine samples. RESULTS: We identified
      2,519 molecular features that were present in all 224 urine samples from the 112
      participants, of which 301 had an ICC of >=0.60. Of the 301 molecular features,
      water arsenic was significantly related to 31 molecular features and urinary
      arsenic was significantly related to 74 molecular features after adjusting for
      multiple comparisons. Six metabolites with a confirmed identity were identified
      from the 82 molecular features that were significantly associated with either
      water arsenic or urinary arsenic after adjustment for multiple comparisons.
      CONCLUSIONS: Our study identified urinary metabolites with long-term
      reproducibility that were associated with arsenic exposure. The data established
      the feasibility of using metabolomics in future larger studies.
      https://doi.org/10.1289/EHP1992.

PMID- 29329107
TI  - Growth and growth hormone: recent papers on efficacy and adverse effects of
      growth hormone and World Health Organisation growth standards.

PMID- 29329105
TI  - Daily sitting time associated with the risk of metabolic syndrome in Korean
      adolescents.
AB  - BACKGROUND: This study aimed to investigate the relationship between daily
      sitting time and the risk of metabolic syndrome in Korean adolescents. METHODS:
      Data from 486 adolescents aged 12-18 years were obtained from national surveys.
      Daily sitting time was measured using questionnaires and divided into three
      intervals: <8 h; 8-12 h; and >=12 h. RESULTS: The mean daily sitting time and
      prevalence of positive metabolic components were 620.9+/-9.9 min/day and 45.5+/
      2.7%, respectively. In a multivariate logistic regression analysis, adolescents
      who sat longer were more likely to have metabolic components (p<0.05),
      independent of age, sex, area of residence, sleeping time and body mass index.
      CONCLUSIONS: Longer daily sitting time appears to be associated with an increased
      risk of metabolic syndrome in adolescents. These findings highlight the need to
      focus on reducing sitting time for all adolescents, not just for those at risk of
      obesity.

PMID- 29329106
TI  - Genetic mutations associated with neonatal diabetes mellitus in Omani patients.
AB  - BACKGROUND: Neonatal diabetes mellitus (NDM) is a rare disorder worldwide where
      diabetes is diagnosed in the first 6 months of life. However, Oman has a
      relatively high incidence of NDM. METHODS: In this study, we investigated the
      genetic etiologies underlying NDM and their prevalence in Oman. We collected a
      cohort of 24 NDM patients, with and without genetic diagnosis, referred to our
      center from 2007 to 2015. All patients without a genetic diagnosis were tested
      for mutations in 23 NDM-associated genes using a custom-targeted next-generation
      sequencing (NGS) panel and methylation analysis of the 6q24 locus. RESULTS: A
      genetic abnormality was detected in 15/24 (62.5%) of our Omani NDM patients. We
      report the detection of 6q24 methylation abnormalities and KCNJ11 mutations for
      the first time in Omani NDM patients. Unlike Western populations where NDM is
      predominantly due to mutations in the KCNJ11, ABCC8 and INS genes, NDM due to
      homozygous GCK gene mutations were most prevalent in Oman, having been observed
      in seven out of 15 NDM patients in whom we established the genetic etiology. This
      reflects the high degree of consanguinity which makes recessive conditions more
      likely. CONCLUSIONS: The results of this study are likely to impact any future
      strategy to introduce genetic testing for NDM disorders within the national
      healthcare system in Oman.

PMID- 29329108
TI  - Cracking novel shared targets between epilepsy and Alzheimer's disease: need of
      the hour.
AB  - Epilepsy and Alzheimer's disease (AD) are interconnected. It is well known that
      seizures are linked with cognitive impairment, and there are various shared
      etiologies between epilepsy and AD. The connection between hyperexcitability of
      neurons and cognitive dysfunction in the progression of AD or epileptogenesis
      plays a vital role for improving selection of treatment for both diseases.
      Traditionally, seizures occur less frequently and in later stages of age in
      patients with AD which in turn implies that neurodegeneration causes seizures.
      The role of seizures in early stages of pathogenesis of AD is still an issue to
      be resolved. So, it is well timed to analyze the common pathways involved in
      pathophysiology of AD and epilepsy. The present review focuses on similar
      potential underlying mechanisms which may be related to the causes of seizures in
      epilepsy and cognitive impairment in AD. The proposed review will focus on many
      possible newer targets like abnormal expression of various enzymes like GSK
      3beta, PP2A, PKC, tau hyperphosphorylation, MMPs, caspases, neuroinflammation and
      oxidative stress associated with number of neurodegenerative diseases linked with
      epilepsy. The brief about the prospective line of treatment of both diseases will
      also be discussed in the present review.

PMID- 29329109
TI  - Cluster analysis and subgrouping to investigate inter-individual variability to
      non-invasive brain stimulation: a systematic review.
AB  - Cluster analysis and other subgrouping techniques have risen in popularity in
      recent years in non-invasive brain stimulation research in the attempt to
      investigate the issue of inter-individual variability - the issue of why some
      individuals respond, as traditionally expected, to non-invasive brain stimulation
      protocols and others do not. Cluster analysis and subgrouping techniques have
      been used to categorise individuals, based on their response patterns, as
      responder or non-responders. There is, however, a lack of consensus and
      consistency on the most appropriate technique to use. This systematic review
      aimed to provide a systematic summary of the cluster analysis and subgrouping
      techniques used to date and suggest recommendations moving forward. Twenty
      studies were included that utilised subgrouping techniques, while seven of these
      additionally utilised cluster analysis techniques. The results of this systematic
      review appear to indicate that statistical cluster analysis techniques are
      effective in identifying subgroups of individuals based on response patterns to
      non-invasive brain stimulation. This systematic review also reports a lack of
      consensus amongst researchers on the most effective subgrouping technique and the
      criteria used to determine whether an individual is categorised as a responder or
      a non-responder. This systematic review provides a step-by-step guide to carrying
      out statistical cluster analyses and subgrouping techniques to provide a
      framework for analysis when developing further insights into the contributing
      factors of inter-individual variability in response to non-invasive brain
      stimulation.

PMID- 29329110
TI  - Prediction of sustained harmonic walking in the free-living environment using raw
      accelerometry data.
AB  - OBJECTIVE: Using raw, sub-second-level accelerometry data, we propose and
      validate a method for identifying and characterizing walking in the free-living
      environment. We focus on sustained harmonic walking (SHW), which we define as
      walking for at least 10 s with low variability of step frequency. APPROACH: We
      utilize the harmonic nature of SHW and quantify the local periodicity of the tri
      axial raw accelerometry data. We also estimate the fundamental frequency of the
      observed signals and link it to the instantaneous walking (step-to-step)
      frequency (IWF). Next, we report the total time spent in SHW, number and
      durations of SHW bouts, time of the day when SHW occurred, and IWF for 49
      healthy, elderly individuals. MAIN RESULTS: The sensitivity of the proposed
      classification method was found to be 97%, while specificity ranged between 87%
      and 97% and the prediction accuracy ranged between 94% and 97%. We report the
      total time in SHW between 140 and 10 min d-1 distributed between 340 and 50
      bouts. We estimate the average IWF to be 1.7 steps-per-second. SIGNIFICANCE: We
      propose a simple approach for the detection of SHW and estimation of IWF, based
      on Fourier decomposition.

PMID- 29329112
TI  - Master protocols in lung cancer: experience from Lung Master Protocol.
AB  - PURPOSE OF REVIEW: Contemporary advances in the understanding of the molecular
      and immunologic basis of metastatic lung cancer have firmly changed its treatment
      paradigm to a personalized, biomarker-driven approach. However, the majority of
      lung-cancer patients [especially lung squamous cell carcinoma (LUSC)] still do
      not have effective targeted therapeutic options. Master protocols, such as Lung
      MAP, represent an innovative clinical trial approach designed to accelerate
      evaluation of novel biomarker-driven therapies. RECENT FINDINGS: Lung-MAP is an
      umbrella trial for advanced LUSC and has been active since 2014. Cumulative
      experience from this overarching, multi-institution master protocol has
      demonstrated that centralized, real-time biomarker screening is feasible and
      substudy modularity is essential for protocol adaptability in a rapidly changing
      treatment landscape. In addition, screening and efficacy results from Lung-MAP
      affirm that LUSC has several putative drivers but remains difficult to
      effectively treat with targeted therapy. SUMMARY: Master protocols are a feasible
      and efficient approach for evaluating biomarker-driven therapies in lung cancer.
      As we begin to target less common genomic and immunotherapy subtypes, centrally
      coordinated clinical trial designs such as Lung-MAP are necessary to rapidly
      deliver effective therapies to patients, whereas also maximizing the quality of
      research data obtained.

PMID- 29329113
TI  - Therapeutic HIV-1 vaccine: time for immunomodulation and combinatorial
      strategies.
AB  - PURPOSE OF REVIEW: The purpose is to recall some of the key immunological
      elements that are at the crossroad and need to be combined for developing a
      potent therapeutic HIV-1 vaccine. RECENT FINDINGS: Therapeutic vaccines and
      cytokines have been commonly used to enhance and/or recall preexisting HIV-1
      specific cell-mediated immune responses aiming to suppress virus replication.
      While the vaccine is important to stimulate HIV-1 specific T-cell responses, the
      cytokine may support the expansion of the stimulated virus-specific T cells.
      Moreover, the current success of immune checkpoint blockers in cancer therapy
      render them very attractive to use in HIV-1 infected individuals, with the
      objective to preserve the function of HIV-specific T cells from exhaustion and
      target directly HIV-1 cell reservoir. More recently, the development of passive
      immunotherapy using broad neutralizing HIV antibodies (bNAbs) and their potential
      capacity to elicit innate or adaptive HIV-cellular responses, beyond their
      neutralizing activity, offers a new opportunity to improve the efficiency of
      therapeutic vaccine. These major advances provide the scientific basis for
      developing potent combinatorial interventions in HIV-1 infected patients.
      SUMMARY: Major advances in our immunological understanding resulting from basic
      science and clinical trials studies have paved the way and established a solid
      platform to jump over the stumbling blocks that prevent the field from developing
      a therapeutic HIV-1 vaccine. It is time for immuno-modulation and combinatorial
      strategies towards HIV-1 eradication.

PMID- 29329111
TI  - Severe peri-ictal respiratory dysfunction is common in Dravet syndrome.
AB  - Dravet syndrome (DS) is a severe childhood-onset epilepsy commonly due to
      mutations of the sodium channel gene SCN1A. Patients with DS have a high risk of
      sudden unexplained death in epilepsy (SUDEP), widely believed to be due to
      cardiac mechanisms. Here we show that patients with DS commonly have peri-ictal
      respiratory dysfunction. One patient had severe and prolonged postictal
      hypoventilation during video EEG monitoring and died later of SUDEP. Mice with an
      Scn1aR1407X/+ loss-of-function mutation were monitored and died after spontaneous
      and heat-induced seizures due to central apnea followed by progressive
      bradycardia. Death could be prevented with mechanical ventilation after seizures
      were induced by hyperthermia or maximal electroshock. Muscarinic receptor
      antagonists did not prevent bradycardia or death when given at doses selective
      for peripheral parasympathetic blockade, whereas apnea, bradycardia, and death
      were prevented by the same drugs given at doses high enough to cross the blood
      brain barrier. When given via intracerebroventricular infusion at a very low
      dose, a muscarinic receptor antagonist prevented apnea, bradycardia, and death.
      We conclude that SUDEP in patients with DS can result from primary central apnea,
      which can cause bradycardia, presumably via a direct effect of hypoxemia on
      cardiac muscle.

PMID- 29329115
TI  - Developing a mitral valve center of excellence.
AB  - PURPOSE OF REVIEW: Despite the proven superiority of mitral repair over
      replacement for degenerative mitral disease, mitral valve replacement remains
      common. Guidelines now recommend referral of patients, particularly those whom
      are asymptomatic, to valve centers of excellence, although criteria that define
      such centers remain to be established. The purpose of this review is to define
      the structure of a mitral center of excellence and to review current clinical
      outcomes which are possible in such a center. RECENT FINDINGS: Recently, American
      College of Cardiology/American Heart Association as well as the European Society
      of Cardiology/European Association of Cardiothoracic Surgery guidelines define
      mitral centers of excellence as either centers in which the likelihood of
      successful and durable repair exceeds 95% and with an operative mortality risk of
      less than 1% (American College of Cardiology/American Heart Association
      definition) or centers with high repair rates, low operative mortality, and a
      record of durable results (European Society of Cardiology/European Association of
      Cardiothoracic Surgery definition). There is however less clarity about the
      structure and function of a center that achieves these outcomes. SUMMARY: The
      importance of centers of excellence in mitral valve surgery are now well
      recognized, and this review will highlight the key components and outcomes of an
      established mitral valve reference center.

PMID- 29329114
TI  - Synovial sarcomas of the upper aero-digestive tract: is there a role for
      conservative surgery?
AB  - PURPOSE OF REVIEW: To present the current state of knowledge concerning the role
      of conservative surgery in the treatment of synovial sarcomas of the upper aero
      digestive tract (UADT). RECENT FINDINGS: The wider experience on synovial
      sarcomas involving the extremities and the results of retrospective reports
      focused on head and neck synovial sarcomas tend to justify a conservative
      surgical approach when dealing with tumors involving the UADT. SUMMARY: UADT
      synovial sarcomas is an extremely rare clinical entity (only around 50 cases
      reported in the literature, with four more herein presented from our own surgical
      series), with no clear guidelines concerning its treatment. Resection should be
      aimed to an en-bloc removal of the tumor within uninvolved surgical margins. In
      fit patients, a conservative surgical approach should be preferred if it does not
      interfere with a complete resection and reasonable functional outcomes. Adjuvant
      treatments (radiotherapy and/or chemotherapy) are frequently needed in view of
      the aggressive behavior of such tumor, but they should be balanced according to
      patient's characteristics and tumor risk factors (grade, size, and previous
      treatments).

PMID- 29329116
TI  - Concussion Symptom Underreporting Among Incoming National Collegiate Athletic
      Association Division I College Athletes.
AB  - OBJECTIVE: Accurate diagnosis of sport-related concussions relies heavily on
      truthful self-reporting of symptom severity. Previous studies have emphasized
      lack of knowledge as a factor in symptom nondisclosure. This study sought to
      examine concussion knowledge and the relationship of knowledge to reasons for
      symptom nondisclosure. DESIGN: Cross-sectional study. SETTING: Data were
      collected during preparticipation athletic evaluations via electronic survey.
      PARTICIPANTS: One hundred fifty-six incoming National Collegiate Athletic
      Association Division I student-athletes. MAIN OUTCOME MEASURES: Survey items
      included previous concussion diagnosis, concussion fact and symptom knowledge,
      reasons and situational contexts for nondisclosure, and stakeholder attitudes.
      RESULTS: Participants, on average, had substantial concussion symptom and fact
      knowledge. Unexpectedly, participants with higher concussion fact knowledge
      endorsed more reasons that athletes may hide symptoms. Concussion symptom
      knowledge was unrelated to reasons for nondisclosure. Athletes believed that
      symptom reporting was less likely in high-stakes versus low-stakes situations and
      consistently identified their teammates as holding attitudes that support
      underreporting and athletic trainers as engaging in behaviors that support player
      safety. CONCLUSIONS: Greater concussion knowledge did not reduce the number of
      reasons that participants viewed as drivers for concussion nondisclosure. In
      other words, participants understood why athletes choose to hide symptoms even
      when they also understood the symptoms, risks, sequelae, and consequences of
      concussion (and potential harm of nondisclosure). Situational contexts and
      important stakeholder attitudes also appeared to importantly influence symptom
      disclosure decisions. A multifaceted approach that goes beyond current
      educational strategies to addresses situational, social, and athletic pressures
      may be needed to initiate a widespread cultural shift away from concussion
      nondisclosure.

PMID- 29329118
TI  - CE: Managing Sepsis and Septic Shock: Current Guidelines and Definitions.
AB  - : Sepsis is a leading cause of critical illness and hospital mortality. Early
      recognition and intervention are essential for the survival of patients with this
      syndrome. In 2002, the Society of Critical Care Medicine (SCCM) and the European
      Society of Intensive Care Medicine (ESICM) launched the Surviving Sepsis Campaign
      (SSC) to reduce overall patient morbidity and mortality from sepsis and septic
      shock by driving practice initiatives based on current best evidence. The SSC
      guidelines have been updated every four years, with the most recent update
      completed in 2016. The new guidelines have increased the focus on early
      identification of infection, risks for sepsis and septic shock, rapid antibiotic
      administration, and aggressive fluid resuscitation to restore tissue perfusion.In
      2014, the SCCM and the ESICM convened a task force of specialists to reexamine
      the definitions of terms used to identify patients along the sepsis continuum. In
      2016, this task force published the Third International Consensus Definitions for
      Sepsis and Septic Shock (Sepsis-3). The new definitions and recommendations
      included tools, based on an updated understanding of the pathobiology of sepsis,
      that can be used to predict adverse outcomes in patients with infection.This
      article discusses the new SSC treatment guidelines, changes in the sepsis bundle
      interventions, and the Sepsis-3 definitions and tools, all of which enable nurses
      to improve patient outcomes through timely collaborative action.

PMID- 29329119
TI  - Effects of Valproic Acid on Morphology, Proliferation, and Differentiation of
      Mesenchymal Stem Cells Derived From Human Gingival Tissue.
AB  - PURPOSE: Valproic acid (VPA), a histone deacetylase inhibitor, has been shown to
      affect cell growth and differentiation in various in vitro and in vivo models.
      The aim of this study is to evaluate the effects of VPA on viability and
      osteogenic differentiation of mesenchymal stem cells derived from the human
      gingival tissue. MATERIALS AND METHODS: Stem cells derived from the gingiva were
      grown in the presence of VPA at concentrations ranging from 0.125 to 8 mM. Cell
      morphology was assessed on days 3, 5, and 7, and cell proliferation was analyzed
      on the same days using a Cell Counting Kit-8 (CCK-8). Alizarin Red-S staining was
      used to assess differentiation of the stem cells. RESULTS: The control group
      showed a normal fibroblast morphology when cultured in growth media. The shape of
      cells in the 8 mM group was more flat than cells in other groups, and fewer cells
      were present. A statistically significant decrease in cell proliferation was seen
      in the 8 mM group. Results of Alizarin Red-S staining showed a significant
      decrease in mineralization in the 8 mM group. CONCLUSIONS: Taken together, this
      study demonstrated that VPA, at the tested concentrations, decreases the
      viability of stem cells derived from the human gingiva. The decreases in
      osteogenic differentiation were achieved via the decrease of Rux2 expression. The
      concentration and application time of VPA treatment should be meticulously
      controlled to minimize any detrimental effects.

PMID- 29329117
TI  - CE: Original Research: Physical Activity Among Chinese American Immigrants with
      Prediabetes or Type 2 Diabetes.
AB  - : : Background: Although the benefits of aerobic exercise and strength training
      for patients with type 2 diabetes have been studied extensively, research on
      physical activity among Chinese American immigrants diagnosed with prediabetes or
      type 2 diabetes has been limited. PURPOSE: We sought to learn more about this
      population's knowledge of physical activity, the types and intensity levels
      performed, and the barriers to such activity. DESIGN AND METHODS: A concurrent
      mixed-methods design was used. The short version of the International Physical
      Activity Questionnaire-Chinese was used to quantitatively measure participants'
      levels of exercise intensity. Semistructured face-to-face interviews were
      conducted to obtain qualitative information regarding participants' knowledge
      about physical activity, the types performed, and the barriers to such activity.
      RESULTS: A total of 100 Chinese American immigrants were recruited for the study
      from January to July 2012 in New York City. On average, participants had lived
      with a diagnosis of prediabetes or type 2 diabetes for 3.3 years and had lived in
      the United States for 21.5 years. Energy expenditure was measured in metabolic
      equivalent of task (MET) units; intensity was measured in cumulative MET-minutes
      per week. The mean total intensity score was 2,744 MET-minutes per week. This was
      achieved mainly through walking. The mean intensity score for walking was 1,454
      MET-minutes per week; the mean duration was 79 minutes per day. Vigorous physical
      activity was least common. The mean intensity score for vigorous physical
      activity was 399 MET-minutes per week, and the mean duration was 17 minutes per
      week. Regarding types of physical activity, the most common were housekeeping,
      walking up stairs, and taking walking or stretching breaks every hour during the
      workday. Based on the interviews, three themes emerged regarding barriers to
      moderate or vigorous physical activity: insufficient education about physical
      activity, health concerns about physical activity, and work-related barriers to
      physical activity. CONCLUSIONS: The majority of Chinese American immigrants with
      prediabetes or type 2 diabetes do not engage in sufficient physical activity,
      performing at a rate significantly below that of the general U.S. POPULATION:
      Increases in the intensity and duration of physical activity should be promoted
      as part of diabetes management for Chinese American immigrants.

PMID- 29329120
TI  - Re-osseointegration of Dental Implants After Periimplantitis Treatments: A
      Systematic Review.
AB  - PURPOSE: This review considers possible surgical treatment modalities for induced
      periimplantitis to regain re-osseointegration as reported in the recent
      literature. MATERIALS AND METHODS: Electronic searches in MEDLINE/PubMed and
      Google Scholar databases were performed on experimental studies considering
      induced periimplantitis and attempts to achieve re-osseointegration from 2003 up
      to December 2016. Conflicts about articles were solved by authors' discussion.
      RESULTS: A total of 15 studies of 159 were finally included in the review.
      DISCUSSION: Various implant surface decontamination techniques chemical and/or
      mechanical have been used either alone or simultaneously with/without guided bone
      regeneration. Despite the access-flap surgery, it was observed that application
      of single decontamination measure either chemical or mechanical was not adequate
      to provide a better treatment outcome. Laser application such as CO2, diode, and
      Er: YAG has been a new treatment approach used for periimplantitis treatment. Er:
      YAG laser had showed no implant surface alteration and provided favorable
      environment for re-osseointegration. CONCLUSION: Promising results were observed
      in the studies that used combination of bone substitutes together with guided
      bone regeneration for the regenerative therapy. Regarding implant surfaces,
      better re-osseointegration was observed with rough implant surfaces rather than
      smooth ones.

PMID- 29329121
TI  - Technique for Preparing Ultrathin and Nanothin Descemet Stripping Automated
      Endothelial Keratoplasty Tissue.
AB  - PURPOSE: To describe and report outcomes of our single-pass microkeratome
      technique for preparation of ultrathin (UT, <=100 MUm) and nanothin (NT, <=50
      MUm) Descemet stripping automated endothelial keratoplasty (DSAEK) grafts.
      METHODS: To prepare NT-DSAEK grafts, a pachymetry nomogram specific to each
      technician and individual microkeratome head was developed based on accumulated
      precut and postcut pachymetry data from previous DSAEK grafts. Mean graft
      thickness as well as precut and postcut endothelial cell counts (ECCs) of NT
      DSAEK, UT-DSAEK, and Descemet membrane endothelial keratoplasty (DMEK) grafts
      between July 2015 and July 2017 were calculated and compared statistically.
      Endothelial cell loss was evaluated using calcein AM stains and ImageJ analysis.
      Postcut graft thickness and rates of perforation/tissue loss for NT-DSAEK grafts
      between May and July 2017 were calculated to determine overall graft preparation
      success rates. RESULTS: Mean postcut graft thickness for all grafts within the NT
      range was 41.0 +/- 6.4 MUm (range 26-50 MUm). Mean ECC did not differ between NT
      DSAEK, UT-DSAEK, and DMEK grafts (P = 0.759 and 0.633, respectively). The overall
      tissue loss rate from attempted NT-DSAEK was 4.8%. Excluding cases of
      perforation, the chance of achieving NT thickness was 60% and within the
      traditional UT range was 100%. CONCLUSIONS: We propose the term "NT-DSAEK" for
      grafts <=50 MUm. The described nomogram allows for standardized creation of NT
      grafts with a low tissue loss rate. This technique is safe and does not result in
      significant ECC loss compared with UT-DSAEK and DMEK grafts. Further studies are
      necessary to corroborate the postsurgical results of NT grafts.

PMID- 29329122
TI  - Some of Us Stay.

PMID- 29329123
TI  - Golf Injuries: Epidemiology, Pathophysiology, and Treatment.
AB  - Increasing numbers of people are playing golf. Golf is a unique sport in that the
      ability to participate at a high level is not limited by age. In addition,
      participants tend to play more rather than less as they grow older. Injuries can
      occur at any point during the golf swing, from takeaway through follow-through.
      Upper extremity injuries can affect the hands, elbow, and shoulder and are
      usually a result of the golf swing at impact. Injuries are also common in the
      lower back as well as the lower extremities. Most injuries are the result of
      overuse and poor swing mechanics. When treating golfers, it is important to have
      a good understanding of the biomechanics and forces of the golf swing to diagnose
      and manage the vast spectrum of injuries incurred in this sport.

PMID- 29329124
TI  - Septic Arthritis of the Wrist.
AB  - Septic arthritis of the wrist is an uncommon condition, but one that can result
      in substantial morbidity. Timely identification and treatment is critical to
      patient care. No serum laboratory values have been shown to consistently confirm
      wrist joint infection. Thus, diagnosis is made based mainly on a thorough patient
      history, physical examination, and joint aspiration. When infection is suspected,
      aspiration of the wrist should be performed to confirm the diagnosis. Broad
      spectrum antibiotics and joint aspiration or surgery are required to manage the
      infection and prevent sequelae.

PMID- 29329125
TI  - On the Horizon From the ORS.

PMID- 29329126
TI  - Case of Congenital Self-Healing Reticulohistiocytosis Expanding the Spectrum of
      Blueberry Muffin Baby.
AB  - Congenital self-healing reticulohistiocytosis (CSHRH) is a benign, rare variant
      of histiocytosis. This condition can present phenotypically as blueberry muffin
      baby. This is the case of a male neonate with skin involvement of papulonodular
      violaceous lesions, which resolved spontaneously. The diagnosis of CSHRH is
      confirmed using histopathology and immunohistochemistry.

PMID- 29329127
TI  - Cutis Laxa Acquisita After Urticarial Vasculitis in SLE Patients.
AB  - Cutis laxa is a rare connective tissue disease involving damage to dermal elastic
      fibers creating a clinical appearance of loose, sagging skin. The condition can
      be either acquired or genetic. Autoimmune diseases, neoplasms, infections, and
      medications have been proposed as the cause of, or in association with, the
      acquired form. In nearly 50% of cases, erythematous plaques present before the
      onset of cutis laxa. Separately, urticarial vasculitis and systemic lupus
      erythematosus have been linked to cutis laxa acquisita. Our case is the first in
      the literature documenting a coexistence of cutis laxa acquisita,
      hypocomplementemic urticarial vasculitis, and systemic lupus erythematosus.

PMID- 29329128
TI  - Expanding the Morphologic Heterogeneity of Stromal Changes in Molluscum
      Contagiosum Infection.

PMID- 29329129
TI  - Primary Cutaneous Spindle Cell Squamous Carcinoma Expressing Smooth Muscle Actin:
      Diagnostic Pitfalls.
AB  - Alpha smooth muscle actin (SMA) belongs to the actin proteins. It is a known
      immunohistochemical marker for tumors of mesenchymal origin. There have been
      reports of expression of SMA in certain epithelial malignancies in the head and
      neck and genital regions. In this study, the authors report a primary cutaneous
      spindle cell squamous carcinoma expressing SMA. Both high- and low-molecular
      weight keratins and p63 were positive, and S100 protein, SOX10, MART-1/Melan-A,
      and muscle-specific actin stains were negative. This case highlights that an
      epithelial tumor could express a mesenchymal marker, thereby making the diagnosis
      problematic.

PMID- 29329130
TI  - Disseminated Warty Papules and Plaques: Question.

PMID- 29329131
TI  - ALK Gene Fusions in Epithelioid Fibrous Histiocytoma: A Study of 14 Cases, With
      New Histopathological Findings.
AB  - Previous studies showed that ALK is often positive in epithelioid fibrous
      histiocytoma (EFH). Two cases of EFH with ALK gene fusions have been recorded.
      Our objective was to study a series of EFH to present histopathological
      variations of EFH, identify novel ALK gene fusions, and determine whether there
      is a correlation between histopathological features and particular gene. We
      investigated 14 cases of EFH, all ALK immunopositive. The cases were assessed
      histopathologically as well as for ALK and TFE-3 rearrangements using FISH and
      ALK gene fusions using next-generation sequencing. The analysis of the sequencing
      results was performed using the Archer Analysis software (v5; ArcherDX Inc). The
      study group consisted of 8 female and 6 male patients, ranging in age from 18 to
      79 years (mean 42 years; median 37.5 years). All presented with a solitary
      lesion. Microscopically, most lesions were polypoid and composed of epithelioid
      cells with ample cytoplasm. In addition, a variable number of bi-, tri-, or
      multinucleated, spindled, multilobated, cells with eccentric nuclei, cells with
      nuclear pseudoinclusions, mucinous, and grooved cells were admixed. In 5 cases,
      the predominant epithelioid cell component consisted of rather small cells,
      whereas spindled cells dominated in 3 cases. Of these, 2 lesions were composed
      rather of pale eosinophilic to clear cells, occasioning a resemblance to PEComa
      or leiomyoma. Immunohistochemically, all cases expressed ALK and 11 were positive
      for TFE-3. The break apart test for ALK was positive in 11 cases, whereas
      specimens from the remaining 3 cases were not analyzable. ALK genes fusions were
      found in all but 3 cases and included SQSTM1-ALK (3), VCL-ALK (3), TMP3-ALK (2),
      PRKAR2A-ALK (1), MLPH-ALK (1), and EML4-ALK (1). No correlation between
      histological features and type of ALK fusion was found. TFE-3 break apart test
      was negative. It is concluded that ALK-immunopositive EFH shows ALK gene fusions
      that involve various protein-coding genes, implicated in a variety of biological
      processes. Rare variants of EFH rather consist of spindled "non-epithelioid"
      cells.

PMID- 29329132
TI  - Cutaneous Nodules and Violaceous Patches on the Legs.

PMID- 29329133
TI  - Cutaneous Angiosarcoma of the Eyelid Mimicking Morbihan Disease.
AB  - BACKGROUND: Cutaneous angiosarcoma presents clinically in numerous ways, and can
      be mistaken for a different clinical entity, particularly when arising at unusual
      anatomic locations such as the eyelid. CASE PRESENTATION: A 57-year-old woman
      presented with a 1-year history of eyelid swelling. Concurrent imaging was also
      suggestive of an edematous process. Multiple superficial biopsies showed
      nonspecific dermal inflammation and interstitial edema. A diagnosis of Morbihan
      disease (chronic and idiopathic lymphedema of the eyelid) was rendered, and the
      patient was treated with compression and local therapy without clinical
      improvement. Three years after initial presentation, a diagnostic blepharoplasty
      was performed revealing a deep dermal vascular proliferation composed of
      anastomosing vascular channels with an atypical endothelial lining. A diagnosis
      of cutaneous angiosarcoma was ultimately made. CONCLUSIONS: This case illustrates
      a unique presentation of cutaneous angiosarcoma and the implications of different
      biopsy techniques in acquiring the correct diagnosis.

PMID- 29329134
TI  - Asymptomatic Acquired Facial Hyperpigmentation.

PMID- 29329135
TI  - Clinician Perceptions of the Importance of Hospital Discharge Components for
      Children.
AB  - BACKGROUND: Discharging hospitalized children involves several different
      components, but their relative value is unknown. We assessed which discharge
      components are perceived as most and least important by clinicians. METHODS:
      March and June of 2014, we conducted an online discrete choice experiment (DCE)
      among national societies representing 704 nursing, physician, case management,
      and social work professionals from 46 states. The DCE consisted of 14 discharge
      care components randomly presented two at a time for a total of 28 choice tasks.
      Best-worst scaling of participants' choices generated mean relative importance
      (RI) scores for each component, which allowed for ranking from least to most
      important. RESULTS: Participants, regardless of field or practice setting,
      perceived "Discharge Education/Teach-Back" (RI 11.1 [95% confidence interval, CI:
      11.0-11.3]) and "Involve the Child's Care Team" (RI 10.6 [95% CI: 10.4-10.8]) as
      the most important discharge components, and "Information Reconciliation" (RI 4.1
      [95% CI: 3.9-4.4]) and "Assigning Roles/Responsibilities of Discharge Care" (RI
      2.8 [95% CI: 2.6-3.0]) as least important. CONCLUSIONS: A diverse group of
      pediatric clinicians value certain components of the pediatric discharge care
      process much more than others. Efforts to optimize the quality of hospital
      discharge for children should consider these findings.

PMID- 29329136
TI  - Glaucoma Implant Tube Lumen Obstruction Visualized Using Anterior Segment Optical
      Coherence Tomography.
AB  - We report a case of glaucoma implant tube lumen obstruction visualized with
      anterior segment optical coherence tomography (ASOCT) and present its surgical
      management. The patient was a 66-year-old man with refractory glaucoma associated
      with traumatic aphakia in the right eye after trabeculectomy, several bleb
      needling procedures, and scleral fixation of the intraocular lens with pars plana
      vitrectomy. Finally, we performed Baerveldt implantation at the pars plana of the
      temporal inferior quadrant with a several Sherwood slit. However, his intraocular
      pressure (IOP) was >30 mm Hg despite maximum medication for several weeks. We
      attempted second vitrectomy and completely removed vitreous around the tube tip;
      however, his IOP remained around 40 mm Hg for several days after the surgery.
      Therefore, we suspected tube obstruction at the extraocular point of the tube
      lumen and used ASOCT for assessment. ASOCT revealed material in the tube lumen.
      We pulled out the tube and then crushed and extruded the obstructing material
      from the tube tip. We then refixed the tube at the same place and achieved good
      IOP control after the surgery. Our findings indicate that ASOCT is useful for
      diagnosing glaucoma implant tube lumen obstruction and surgical decision-making.

PMID- 29329137
TI  - Macular and Multifocal PERG and FD-OCT in Preperimetric and Hemifield Loss
      Glaucoma.
AB  - PURPOSE: To evaluate the ability of macular and multifocal (mf) pattern
      electroretinogram (PERG) to differentiate preperimetric glaucoma (PG) and
      glaucoma with hemifield loss (GHL) from controls, to compare the discrimination
      ability of PERG and fourier-domain optical coherence tomography (FD-OCT), and to
      assess the relationship between measurements. PATIENTS AND METHODS: Standard
      automated perimetry, steady-state and transient PERG and mfPERG measurements were
      obtained from PG (n=14, 24 eyes), GHL (n=5, 7 eyes), and controls (n=19, 22
      eyes). Circumpapillary retinal nerve fiber layer (cpRNFL), full-thickness macula,
      and segmented macular layer thicknesses on FD-OCT were investigated. Measurements
      were compared using mixed effects linear models. The relationships between
      measurements and the diagnostic performance of each technology were assessed.
      RESULTS: Compared with controls, average P50 peak time transient PERG responses
      were reduced in PG and GHL, whereas average latency and amplitude steady-state
      and mfPERG responses were abnormal only in GHL. cpRNFL and macular thickness
      measurements in PG and GHL differed significantly from controls. A significant
      relationship was found between PERG and most FD-OCT or SAP parameters. Partial
      least squares discriminant analysis revealed that OCT parameters, along with
      mfPERG and transient PERG parameters had similar ability to discriminate PG and
      GHL from healthy controls. CONCLUSIONS: PERG and OCT parameters may be abnormal,
      with significant correlations between measurements, in PG eyes. Both technologies
      may be useful for detection of early glaucoma.

PMID- 29329138
TI  - Relationship of Macular Thickness and Function to Optical Microangiography
      Measurements in Glaucoma.
AB  - PURPOSE: The purpose of this article was to evaluate the relationship between
      macular optical microangiography (OMAG), ganglion cell-inner plexiform layer
      (GCIPL) thickness, and visual sensitivity measurements of different macular
      sectors in primary open-angle glaucoma. METHODS: In a cross-sectional study, 39
      eyes of 26 primary open-angle glaucoma patients underwent optical coherence
      tomography imaging and 10-2 visual field examination of the macula in the same
      session. Linear regression models were used to evaluate the relationships between
      OMAG, GCIPL thickness, and visual sensitivity measurements in different macular
      sectors. Strength of relationship was reported as coefficient of determination
      (R). RESULTS: R values for the associations between OMAG and GCIPL thickness
      measurements ranged from 0.37 in the temporal sector to 0.56 in the inferior
      macular sector. R values for the association between OMAG and visual sensitivity
      measurements ranged from 0.23 in the superior to 0.53 in the inferior macular
      sector. R values for the association between GCIPL thickness and visual
      sensitivity measurements ranged from 0.15 in the superior to 0.62 in the temporal
      sector. CONCLUSIONS: The strongest associations between OMAG, GCIPL thickness,
      and visual sensitivity measurements were found in the inferior macular sector.
      The association of OMAG with GCIPL thickness measurements was as strong as the
      association between OMAG and visual sensitivity measurements in the inferior
      macular sector.

PMID- 29329139
TI  - Diagnostic Ability and Structure-function Relationship of Peripapillary Optical
      Microangiography Measurements in Glaucoma.
AB  - PURPOSE: The aim of this study was to evaluate the diagnostic abilities of
      peripapillary optical microangiography (OMAG) measurements in eyes with primary
      open-angle glaucoma (POAG) and to evaluate the relationship of these measurements
      with retinal nerve fiber layer (RNFL) thickness and visual sensitivities in
      different peripapillary sectors. METHODS: In a cross-sectional study, 97 eyes of
      57 control subjects and 101 eyes of 66 POAG patients underwent OMAG and RNFL
      imaging with optical coherence tomography. POAG was diagnosed on the basis of the
      masked evaluation of optic disc stereo photographs. Area under receiver operating
      characteristic curves and sensitivities at 90% specificity of the OMAG and RNFL
      thickness measurements in different peripapillary sectors were evaluated.
      Association between OMAG, RNFL thickness, and visual sensitivity measurements
      were evaluated using fractional polynomial regression models. RESULTS: All OMAG
      and RNFL measurements were significantly less in the POAG compared with the
      control eyes. Diagnostic abilities of the best OMAG measurement (inferior sector
      vessel length density, area under receiver operating characteristic curves: 0.84,
      sensitivity at 90%, specificity: 65%) were significantly less (P<0.05) than that
      of the best RNFL measurement (inferior sector RNFL thickness, 0.94 and 81%).
      Inferior sector vessel length density showed the strongest association with
      inferior sector RNFL thickness (R=0.66, P<0.001) and the superior sector visual
      sensitivity loss (R=0.21, P=0.006). CONCLUSIONS: The inferior sector OMAG
      measurements had the best diagnostic ability in glaucoma and the strongest
      association with RNFL and the visual sensitivity measurements. Diagnostic ability
      of OMAG measurements, however, were significantly less than the RNFL thickness
      measurements.

PMID- 29329140
TI  - Slit-lamp Needling of the Anterior Capsule for Aqueous Misdirection After
      Hyaloido-zonulectomy and Iridectomy.
AB  - INTRODUCTION: We present a case of persistent aqueous misdirection, after Ahmed
      glaucoma valve surgery, despite undergoing an anterior vitrectomy with hyaloido
      zonulectomy and iridectomy. CASE REPORT: A 73-year-old female patient, 4 months
      after phacotrabeculectomy, was referred with persistent high intraocular pressure
      (IOP). Postoperatively, she developed aqueous misdirection with a flat anterior
      chamber (AC) but with an IOP of 15 mm Hg. On presentation, her AC was shallow
      with peripheral iris-cornea touch, and her IOP was 39 mm Hg. Posterior Nd:Yag
      capsulotomy with disruption of anterior hyaloid face partially deepened the AC.
      With failure of the trabeculectomy and high IOP, an Ahmed valve was placed. On
      the first operative day the AC was deep with an IOP of 10 mm Hg. On day 6 the
      patient presented with pain, flat AC, and an IOP of 10 mm Hg. Fundus examination
      revealed no choroidal effusion. Despite repeated reformation with viscoelastic,
      the AC failed to deepen. An anterior vitrectomy with hyaloido-zonulectomy was
      performed. Initially, the AC was deep, but, a few days later, it was flat.
      Multiple reformations and vitreous tap failed to keep the AC deep. A 30-G needle
      was passed at the slit lamp across the temporal cornea, iris, and anterior
      capsule into the anterior vitreous cavity. The needle was then partially
      withdrawn and used to create a space between the intraocular lens and anterior
      capsule. This immediately deepened the AC and remained so for the duration of
      follow-up (4 mo). CONCLUSION: Slit-lamp needling of the anterior lens capsule can
      be successfully performed to help resolve a persistent case of aqueous
      misdirection after anterior vitrectomy.

PMID- 29329141
TI  - Precision of Optic Nerve Head and Retinal Nerve Fiber Layer Parameter
      Measurements by Spectral-domain Optical Coherence Tomography.
AB  - PURPOSE: The aim of this study was to assess the repeatability and
      reproducibility (R&R) of Bruch membrane opening based on minimum rim width (BMO
      MRW), minimum rim area (BMO-MRA) and peripapillary retinal nerve fiber layer
      thickness (RNFLT) with the Spectralis optical coherence tomography (Heidelberg
      Engineering) for normal and glaucoma subjects. Precise measurement of these
      parameters can support detection of structural glaucomatous damage and
      progression. METHODS: This cross-sectional study included 16 healthy controls and
      16 patients with glaucoma. One eye was randomly selected and included in this
      study. Subjects underwent 1 baseline and 3 follow-up measurements, using 3
      different Spectralis optical coherence tomography devices in randomized order,
      each operated by a single operator. Outcome measures were global and sectorial
      averages of BMO-MRW and BMO-MRA, and of peripapillary RNFLT obtained from
      12/14/16-degree circle scans. Coefficients of variation (COV) were calculated and
      a mixed-effects analysis of variance was performed to compare R&R between
      devices. RESULTS: COVs of global and sectorial BMO-MRW measurement under
      repeatability conditions ranged from 0.51% to 1.7% (normal, 0.62% to 1.3%;
      glaucoma, 0.64% to 2.3%). Respective COVs under reproducibility conditions ranged
      from 0.89% to 1.9% (normal, 0.77% to 2.8%; glaucoma, 1.1% to 2.6%). COVs of
      global and sectorial RNFLT measurements under repeatability conditions ranged
      from 0.5% to 2.8%. Respective COVs under reproducibility conditions ranged from
      1.6% to 3.5%. CONCLUSIONS: For R&R, the COVs of measured parameters were by trend
      higher for glaucoma eyes compared with normal controls. The BMO-MRW measurement
      system has an excellent precision taking into account that major and minor
      corrections of segmentation have to be done by the examiner before evaluation.

PMID- 29329142
TI  - Whole-genome methylation profiling of peripheral blood mononuclear cell for acute
      exacerbations of chronic obstructive pulmonary disease treated with
      corticosteroid.
AB  - OBJECTIVE: Although association studies in the general population may be relevant
      for determining susceptibility to chronic obstructive pulmonary disease (COPD),
      they may be less applicable for pharmacogenetics research in participants who
      have already acquired the disease. PATIENTS AND METHODS: A genome-wide
      methylation profiling (generated by HumanMethylation450 BeadChips study was
      performed on peripheral blood mononuclear cells of 24 patients with AECOPD (acute
      exacerbation COPD), with good and poor responsiveness to standard corticosteroid
      treatment. Pyrosequencing was used to replicate the selected CpG sites in 50
      patients with AECOPD with standard corticosteroid treatment. RESULTS: The results
      showed the patients with AECOPD with good and poor response to standard
      corticosteroid treatment have a distinct DNA methylation pattern. A total of 23
      CpG loci located in 19 known gene regions, including gene-body and promoter,
      appeared to be significantly differentially methylated. Replication by
      pyrosequencing revealed that one CpG site in PSMD8 showed the same trend of
      differential methylation and reached to statistical significance as the
      microarray result. CONCLUSION: Our preliminary findings provide evidence for
      molecular heterogeneity in patients with AECOPD, which may contribute to
      significant differences in their response to COPD treatment.

PMID- 29329143
TI  - Wellness, stress, balance...and resilience.

PMID- 29329144
TI  - Cybersecurity matters.
AB  - How to safeguard patient and other sensitive data.

PMID- 29329145
TI  - Orthopaedic Management of Leg-length Discrepancy in Proteus Syndrome: A Case
      Series.
AB  - INTRODUCTION: Proteus syndrome (PS) is a rare mosaic disorder comprising
      asymmetric bony and soft tissue overgrowth leading to significant morbidity.
      Placement of growth inhibition hardware with subsequent epiphyseal arrest
      improves leg-length and angular deformities in pediatric patients without PS. The
      purpose of this study was to review the surgical approach and present outcomes,
      complications, and recommendations in 8 patients with PS and leg-length
      discrepancy (LLD). METHODS: We conducted a retrospective chart review of 8
      patients with PS whose primary reason for surgery was LLD. Patients were eligible
      if they met clinical diagnostic criteria for PS and if the National Institutes of
      Health team performed at least 1 of their surgical interventions between 2005 and
      2015. Surgical techniques included growth inhibition, with tension band plates,
      applied >=1 times, and epiphyseal arrest. RESULTS: Eight patients, followed for
      an average of 4.6 years (range, 1.0 to 7.1 y) after the index procedure, were
      included in this analysis. Average age at first LLD surgery was 9.4 years (range,
      6.1 to 13.6 y); the average LLD was 3.4 cm (range, 0.4 to 7.0 cm) at
      presentation, and 5.0 cm (range, 1.8 to 10.0 cm) at the time of the first LLD
      surgery. Participants underwent 23 total surgeries (range, 1 to 5 per patient)
      and 7 patients have completed surgical intervention. For the 7 patients who did
      not require overcorrection the average LLD at the last clinical encounter was 2.6
      cm (range, 0.6 to 7.2 cm). We encountered 2 complications: 2 patients developed
      mild knee valgus, which responded to standard guided growth techniques.
      CONCLUSIONS: This case series suggests that growth inhibition and epiphyseal
      arrest in children with PS can reduce LLD with few complications. Careful
      monitoring, rapid mobilization, deep venous thrombosis prophylaxis, and
      sequential compression devices were also integral elements of our surgical
      protocol. LEVEL OF EVIDENCE: Level IV.

PMID- 29329146
TI  - National Prevalence and Effects of Multiple Chemical Sensitivities.
AB  - OBJECTIVE: The aim of this study was to assess the prevalence of multiple
      chemical sensitivities (MCS), its co-occurrence with asthma and fragrance
      sensitivity, and effects from exposure to fragranced consumer products. METHODS:
      A nationally representative cross-sectional population-based sample of adult
      Americans (n = 1137) was surveyed in June 2016. RESULTS: Among the population,
      12.8% report medically diagnosed MCS and 25.9% report chemical sensitivity. Of
      those with MCS, 86.2% experience health problems, such as migraine headaches,
      when exposed to fragranced consumer products; 71.0% are asthmatic; 70.3% cannot
      access places that use fragranced products such as air fresheners; and 60.7% lost
      workdays or a job in the past year due to fragranced products in the workplace.
      CONCLUSION: Prevalence of diagnosed MCS has increased over 300%, and self
      reported chemical sensitivity over 200%, in the past decade. Reducing exposure to
      fragranced products could help reduce adverse health and societal effects.

PMID- 29329147
TI  - Multisource Feedback and Narrative Comments: Polarity, Specificity,
      Actionability, and CanMEDS Roles.
AB  - INTRODUCTION: Multisource feedback is a questionnaire-based assessment tool that
      provides physicians with data about workplace behaviors and may combine numeric
      and narrative (free-text) comments. Little attention has been paid to wording of
      requests for comments, potentially limiting its utility to support physician
      performance. This study tested the phrasing of two different sets of questions.
      METHODS: Two sets of questions were tested with family physicians, medical and
      surgical specialists, and their medical colleague and coworker respondents. One
      set asked respondents to identify one thing the participant physician does well
      and one thing the physician could target for action. Set 2 questions asked what
      does the physician do well and what might the physician do to enhance practice.
      Resulting free-text comments provided by respondents were coded for polarity
      (positive, neutral, or negative), specificity (precision and detail),
      actionability (ability to use the feedback to direct future activity), and
      CanMEDS roles (competencies) and analyzed descriptively. RESULTS: Data for 222
      physicians (111 physicians per set) were analyzed. A total of 1824 comments
      (8.2/physician) were submitted, with more comments from coworkers than medical
      colleagues. Set 1 yielded more comments and were more likely to be positive, semi
      specific, and very actionable than set 2. However, set 2 generated more very
      specific comments. Comments covered all CanMEDS roles with more comments for
      collaborator and leader roles. DISCUSSION: The wording of questions inviting free
      text responses influences the volume and nature of the comments provided.
      Individuals designing multisource feedback tools should carefully consider
      wording of items soliciting narrative responses.

PMID- 29329148
TI  - Self-reported Health Status Differs for Amazon's Mechanical Turk Respondents
      Compared With Nationally Representative Surveys.
AB  - BACKGROUND: Amazon's Mechanical Turk (MTurk) platform has become a data source
      for peer-reviewed academic research publications, with over 24,000 Google Scholar
      search results. Although well-developed and supportive in other disciplines, the
      literature in health and medicine comparing results from samples generated on
      MTurk to gold standard, nationally representative health and medical surveys is
      beginning to emerge. OBJECTIVE: To compare the demographic, socioeconomic, and
      self-reported health status variables in an MTurk sample to those from 2
      prominent national probability surveys, including the Medical Expenditure Panel
      Survey (MEPS) and the Behavioral Risk Factor Surveillance System (BRFSS).
      RESEARCH DESIGN: We analyze weighted and unweighted tabulations of the MTurk,
      MEPS, and BRFSS. Wald tests identify statistical significance. MEASURES:
      Demographic, socioeconomic, and health status variables in an adult MTurk sample
      collected in 2016 (n=1916), the 2015 MEPS household survey component (n=21,210),
      and the 2015 BRFSS (n=283,502). RESULTS: Our findings indicate statistically
      significant differences in the demographic, socioeconomic, and self-perceived
      health status tabulations in the MTurk sample relative to the unweighted and
      weighted MEPS and BRFSS. The MTurk sample is more likely to be female (65.8% in
      MTurk, 50.9% in MEPS, 50.2% in BRFSS), white (80.1% in MTurk, 76.9% in MEPS, and
      73.9% in BRFSS), non-Hispanic (91.1%, 82.4%, and 81.4%, respectively), younger,
      and less likely to report excellent health status (6.8% in MTurk, 28.3% in MEPS,
      and 20.2% in BRFSS). CONCLUSIONS: We find significant differences across
      variables that warrant hesitation in using MTurk data as a replacement for the
      gold standard datasets in health services research.

PMID- 29329149
TI  - Author Response for An Electronic Health Record-based Intervention to Promote
      Hepatitis C Virus Testing Among Adults Born Between 1945 and 1965: A Cluster
      randomized Trial.

PMID- 29329150
TI  - Comparison of Iodine Density Measurement Among Dual-Energy Computed Tomography
      Scanners From 3 Vendors.
AB  - OBJECTIVES: The aims of this study were to analyze the effect of dual-energy
      computed tomography (DECT) scanners and fluid characteristics on iodine
      quantification and to calculate the measurement variability range induced by
      those variables. METHODS: We performed an experimental phantom study with 4
      mediastinal iodine phantoms. Each phantom contained 6 tubes of different iodine
      concentrations (0, 1.0, 2.5, 5.0, 10.0, and 20.0 mg/mL) diluted in a specific
      solvent, which was water, 10% amino acid solution, 20% lipid emulsion, or 18%
      calcium solution, respectively. Mediastinal phantoms were inserted into an
      anthropomorphic chest phantom and were scanned with 3 different DECT scanners
      from 3 vendors using 2 radiation dosage settings. Iodine density (IoD) and
      computed tomography (CT) attenuation at virtual monoenergetic 70-keV images and
      virtual nonenhanced images were measured for the iodine phantoms. The effects of
      DECT scanners, solvents, and radiation dosage on the absolute measurement error
      of IoD and on the CT attenuation profiles were investigated using linear mixed
      effects models. Measurement variability range of IoD was also determined.
      RESULTS: Absolute error of IoD was not significantly affected by the DECT
      systems, kind of solvents, and radiation dosage settings. However, CT attenuation
      profiles were significantly different among the DECT vendors and simulated body
      fluids. Measurement variability range of IoD was from -0.6 to 0.4 mg/mL for the
      true iodine concentration 0 mg/mL. CONCLUSIONS: Dual-energy CT systems and fluid
      characteristics did not have a significant effect on the IoD measurement
      accuracy. A cutoff of IoD for the determination of a truly enhancing lesion on
      DECT would be 0.4 mg/mL.

PMID- 29329152
TI  - Remotely Supervised Transcranial Direct Current Stimulation After ECT Improves
      Mood and Cognition in a Patient With Multiple Sclerosis: A Case Study.

PMID- 29329153
TI  - Limiting Legal Intrusions in ECT Practice, a Commentary on "Regulation of
      Electroconvulsive Therapy: A Systematic Review of US State Laws".

PMID- 29329151
TI  - Gadolinium Retention, Brain T1 Hyperintensity, and Endogenous Metals: A
      Comparative Study of Macrocyclic Versus Linear Gadolinium Chelates in Renally
      Sensitized Rats.
AB  - OBJECTIVES: This preclinical study was designed to compare gadolinium (Gd) brain
      uptake after repeated injections of a macrocyclic Gd-based contrast agent (GBCA)
      (gadoterate meglumine) or 2 linear GBCAs (L-GBCAs) (gadobenate dimeglumine or
      gadodiamide) on a translational model of moderate renal impairment in rats.
      METHODS: The study was carried out in subtotally nephrectomized rats. Animals
      received 4 intravenous injections per week of GBCA (gadoterate meglumine,
      gadobenate dimeglumine, or gadodiamide) for 5 weeks, resulting in a cumulative
      dose of 12 mmol/kg, followed by a 1-month injection-free period. T1
      hyperintensity in the deep cerebellar nuclei (DCNs) was investigated, and brain
      structures were carefully dissected to determine elemental Gd, iron (Fe), copper
      (Cu), and zinc (Zn) distribution by mass spectrometry. Urinary excretion of
      endogenous metals was also investigated soon after GBCA administration and
      several days later in order to assess a potential transmetalation phenomenon.
      RESULTS: Unlike gadoterate, repeated injections of L-GBCAs gadobenate and
      gadodiamide both induced T1 hyperintensity in the DCNs. Fine dissection of
      cerebral and cerebellar structures demonstrated very low levels or absence of Gd
      after repeated injections of gadoterate, in contrast to the two L-GBCAs, for
      which the highest total Gd concentration was demonstrated in the DCNs (Gd
      concentration in DCNs after 4.5 weeks of injection-free period: 27.1 +/- 6.5
      nmol/g for gadodiamide [P < 0.01 vs saline and P < 0.05 vs gadoterate]; 12.0 +/-
      2.6 nmol/g for gadobenate [P < 0.09 vs saline]; compared with 1.4 +/- 0.2 nmol/g
      for gadoterate [ns vs saline]). The distribution of Gd concentration among the
      various brain structures dissected was also well correlated with the Fe
      distribution in these structures. No difference in endogenous metal levels in
      brain structures was observed. However, injection of gadobenate or gadodiamide
      resulted in an increase in urinary Zn excretion (urinary Zn concentrations: 57.9
      +/- 20.5 nmol/mL with gadobenate [P < 0.01 vs gadoterate and saline] and 221.6 +/
      83.3 nmol/L with gadodiamide [P < 0.0001 vs all other treatments] vs 8.1 +/- 2.3
      nmol/L with saline and 10.6 +/- 4.8 nmol/L with gadoterate]). CONCLUSIONS: In a
      model of renally impaired rats, only traces of gadoterate meglumine were detected
      in the brain with no T1 hyperintensity of the DCNs, whereas marked Gd retention
      was observed in almost all brain areas after injections of the L-GBCAs,
      gadobenate dimeglumine and gadodiamide. Brain structures with higher Gd uptake
      corresponded to those structures containing more Fe. Urinary Zn excretion was
      significantly increased after a single injection of L-GBCAs.

PMID- 29329154
TI  - Effects on Volume Load and Ratings of Perceived Exertion in Individuals Advanced
      Weight-Training After Transcranial Direct Current Stimulation.
AB  - The aim of this study was investigate the effects of transcranial direct current
      stimulation (tDCS) on volume-load and ratings of perceived exertion. Fifteen
      young healthy individuals, aged between 20 and 30 years in advanced strength
      training were recruited. Test and retest of the 10 maximum repetitions (10RM)
      were performed to determine the reliability of load utilized. Subjects performed
      three experimental conditions in a randomized, double-blinded crossover design:
      anodic stimulation (a-tDCS), cathodic stimulation (c-tDCS) and sham (2 mA for 20
      minutes targeting the dorsolateral prefrontal cortex cortex left). Immediately
      after the experimental conditions, subjects completed one set of maximum
      repetitions with 10RM load (volume-load) and answered to OMNI-RES (Post
      stimulation) (level of significance p <= 0.05). The volume-load showed main
      effect for condition (F(2, 28)= 164.801; p<0.001). In post-stimulation, a-tDCS
      was greater than c-tDCS (p <= 0.001), and sham (p <= 0.001). For ratings of
      perceived exertion (OMNI-RES), the results showed main effect for condition (F(2,
      28)=9.768; p <= 0.05). In post-stimulation, c-tDCS was greater than a-tDCS (p <=
      0.05), and sham (p <= 0.05). We conclude that the use of a-tDCS may promote
      increased in volume-load for the LP45 exercise. Moreover, higher-volume loads are
      necessary to maximize muscle strength and anabolism.

PMID- 29329155
TI  - Ecological validity and reliability of an age-adapted endurance field test in
      young male soccer players.
AB  - The purpose of this study was to examine the reliability and the association with
      relevant match activities (ecological validity) of an age-adapted field test for
      intermittent high-intensity endurance known as Yo-Yo intermittent recovery level
      1 children test (YYIR1C) in young male soccer players. Twenty-eight young male
      outfield soccer players (age 11.1+/-0.9 years, height 142+/-4.4 cm, body mass
      37.0+/-5.9 kg) with at least 2 years of experience in soccer competitions were
      tested twice using YYIR1C and an age-adapted competitive small-sided game (i.e.,
      9v9), 7 days apart in a random order. The YYIR1C performance showed an excellent
      relative (ICC=0.94) and a good absolute reliability (TEM as %CV=5.1%). Very large
      and significant associations were found between YYIR1C performance and match high
      intensity activity (r=0.53). Large correlations were found between YYIR1C and
      match sprinting (r=0.42) and high-intensity metabolic power (r=0.46) distances.
      Match total distance was largely associated with YYIR1C (r=0.30). The results of
      this study showed that YYIR1C may be considered a valid and reliable field test
      for assessing intermittent high-intensity endurance in young male soccer players.
      Due to the relevance of aerobic fitness in youth soccer, future studies testing
      the sensitiveness of YYIR1C are necessary.

PMID- 29329156
TI  - Impact of Integrated Health Care Delivery on Racial and Ethnic Disparities in
      Pancreatic Cancer.
AB  - OBJECTIVES: The objective of this study was to evaluate whether disparities in
      pancreatic cancer diagnosis, treatment, and survival are reduced in an integrated
      health system. METHODS: We conducted a retrospective study (2006-2014) among
      patients with pancreatic cancer from Kaiser Permanente Southern California.
      Racial ethnic groups included non-Hispanic whites (NHW), non-Hispanic blacks
      (NHB), Hispanics, and Asians. We used multivariable and Cox regression analyses
      to evaluate disparities in diagnosis and treatment utilization (oncology care,
      surgery, time to surgery, chemotherapy) and overall survival, respectively.
      RESULTS: Among 2103 patients, 54% were diagnosed with stage IV disease, 80%
      received oncology consultation, 20% received surgery with mean time to surgery 27
      days (standard deviation, 36.8), 50.4% received chemotherapy. Mean overall
      survival was 8.6 months (standard deviation, 11.5). There were no differences in
      odds of stage IV diagnosis, oncology consultation, surgery, or time to surgery by
      racial ethnic group. Asians were more likely to receive chemotherapy (odds ratio,
      1.59; 95% confidence interval [CI], 1.09-2.32) compared to NHW. NHB (hazard
      ratio, 0.78; 95% CI, 0.67-0.91) and Asians (hazard ratio, 0.81; 95% CI, 0.66
      1.00) had improved survival compared to NHW. CONCLUSIONS: Minorities were not
      disadvantaged in pancreatic cancer care. Improved health care coordination may
      improve current disparities.

PMID- 29329157
TI  - Smad4 Loss Correlates With Higher Rates of Local and Distant Failure in
      Pancreatic Adenocarcinoma Patients Receiving Adjuvant Chemoradiation.
AB  - OBJECTIVES: The tumor suppressor gene SMAD4 (DPC4) is genetically inactivated in
      approximately half of pancreatic ductal adenocarcinomas (PDAs). We examined
      whether Smad4 tumor status was associated with outcomes after adjuvant
      chemoradiation (CRT) for resected PDAs. METHODS: Patients treated with adjuvant
      CRT were identified (N = 145). Smad4 status was determined by immunolabeling and
      graded as intact or lost. Kaplan-Meier method and multivariable competing risk
      analyses were performed. RESULTS: On multivariate competing risk analysis, Smad4
      loss was associated with increased risk of local recurrence (LR) (hazard ratio,
      2.37; 95% confidence interval, 1.10-5.11; P = 0.027), distant failure (DF)
      (hazard ratio, 1.71; 95% confidence interval, 1.03-2.83; P = 0.037), and
      synchronous LR and DF at first recurrence (14.9 % vs 5.3%, P = 0.07) compared
      with Smad4 intact cancers. Smad4 loss was not associated with median overall
      survival (22 vs 22 months; P = 0.63) or disease-free survival (lost [13.6 months]
      vs intact [13.5 months], P = 0.79). CONCLUSIONS: After PDA resection and adjuvant
      CRT, Smad4 loss correlated with higher risk of LR and DF, but not with survival.
      Smad4 loss may help predict which surgical patients are at higher risk for
      failure after definitive management and may benefit from intensified adjuvant
      therapy.

PMID- 29329158
TI  - Expression of Gastrin Family Peptides in Pancreatic Islets and Their Role in beta
      Cell Function and Survival.
AB  - OBJECTIVES: Modulation of cholecystokinin (CCK) receptors has been shown to
      influence pancreatic endocrine function. METHODS: We assessed the impact of the
      CCKA and CCKB receptor modulators, (pGlu-Gln)-CCK-8 and gastrin-17, respectively,
      on beta-cell secretory function, proliferation and apoptosis and glucose
      tolerance, and investigating alterations of CCK and gastrin islet expression in
      diabetes. RESULTS: Initially, the presence of CCK and gastrin, and expression of
      their receptors were evidenced in beta-cell lines and mouse islets. (pGlu-Gln)
      CCK-8 and gastrin-17 stimulated insulin secretion from BRIN-BD11 and 1.1B4 beta
      cells, associated with no effect on membrane potential or [Ca]i. Only (pGlu-Gln)
      CCK-8 possessed insulin secretory actions in isolated islets. In agreement, (pGlu
      Gln)-CCK-8 improved glucose disposal and glucose-induced insulin release in mice.
      In addition, (pGlu-Gln)-CCK-8 evoked clear satiety effects. Interestingly, islet
      colocalization of CCK with glucagon was elevated in streptozotocin- and
      hydrocortisone-induced diabetic mice, whereas gastrin coexpression in alpha cells
      was reduced. In contrast, gastrin colocalization within beta-cells was higher in
      diabetic mice, while CCK coexpression with insulin was decreased in insulin
      deficient mice. (pGlu-Gln)-CCK-8 and gastrin-17 also augmented human and rodent
      beta-cell proliferation and offered protection against streptozotocin-induced
      beta-cell cytotoxicity. CONCLUSIONS: We highlight the direct involvement of CCKA
      and CCKB receptors in pancreatic beta-cell function and survival.

PMID- 29329159
TI  - Overexpression of the Long Noncoding RNA HomeoboxA Transcript at the Distal Tip
      Predicts Poor Prognosis in a KRAS-Independent Manner in Periampullary Region
      Tumors.
AB  - OBJECTIVES: Periampullary region tumors (PRTs) are the fifth highest cause of
      cancer-related deaths worldwide. Although recent studies have highlighted the
      prognostic value of the long noncoding RNA HomeoboxA transcript at the distal tip
      (HOTTIP) in patients with pancreatic ductal adenocarcinoma, the relationship
      between HOTTIP and clinical outcome of all PRTs remains obscure. The aim of this
      study was to clarify the prognostic significance of HOTTIP in patients with all
      PRTs related to KRAS mutational status. METHODS: HomeoboxA transcript at the
      distal tip expression was detected in 100 PRT samples using quantitative real
      time polymerase chain reaction. The associations between HOTTIP levels,
      clinicopathological factors, and patient prognosis were also analyzed. RESULTS:
      The expression of HOTTIP was found to be significantly upregulated by 32-fold (P
      = 0.031) in tumor tissues compared with normal tissues. The over expression of
      HOTTIP was related with presence of invasion and metastasis (P = 0.0467, P =
      0.0256). In addition, increased HOTTIP expression was associated with poor
      prognosis independent of KRAS mutation (P < 0.001; n = 72). Moreover,
      multivariate analysis showed that high HOTTIP expression was an unfavorable
      prognostic factor for overall survival. CONCLUSIONS: Our findings indicate that
      high levels of HOTTIP expression have the potential to be an independent,
      unfavorable prognostic factor for patients with PRT.

PMID- 29329160
TI  - Predictive Effect of the Total Number of Examined Lymph Nodes on N Staging and
      Survival in Pancreatic Neuroendocrine Neoplasms.
AB  - OBJECTIVES: We aim to examine the predictive effect of the total number of
      examined lymph nodes on N stage and survival in pancreatic neuroendocrine
      neoplasms (pNENs) and to determine the optimal threshold. METHODS: A pNENs data
      set from 2004 to 2013 was extracted from the Surveillance, Epidemiology, and End
      Result database. Multivariate logistic regression and Cox proportional hazards
      model were used to identify predictive factors associated with N stage and
      survival, respectively. RESULTS: Totally, 1280 pNENs were analyzed. The 11 to 15
      lymph nodes examined showed a strong association with the N1 stage (6-10 vs 11
      15: odds ratio, 0.672; P = 0.042; 11-15 vs 16-20: odds ratio, 1.049; P = 0.840).
      However, it failed to show any survival benefit in pNENs with or without lymph
      node metastasis. CONCLUSIONS: Examining at least 11 lymph nodes may be useful to
      accurately classify the N stage for pNENs.

PMID- 29329161
TI  - Utility of Endoscopic Ultrasonography Screening for Small Pancreatic Cancer and
      Proposal for a New Scoring System for Screening.
AB  - OBJECTIVES: This study aimed to evaluate the utility of endoscopic
      ultrasonography screening for small pancreatic cancer (PC) and propose a new
      simple scoring system for selecting individuals who should be screened. METHODS:
      Risk factors or symptoms related to PC were tentatively divided into high- and
      low-grade risk groups based mainly on reported relative risk values. Numbers of
      risk factors were designated as risk scores. Endoscopic ultrasonography screening
      was performed for 632 individuals. We analyzed scores for PC detection
      prospectively, and risk factors and scores of PC patients retrospectively.
      RESULTS: We detected 10 small malignant pancreatic neoplasms (size <=20 mm; 8
      PCs; 9 Tis or T1) and 14 advanced PCs. All small PCs and 95.5% of PCs were found
      in individuals with low-grade risk scores of at least 3 points (P) or high-grade
      risk scores of at least 1P. Both average risk scores were significantly higher in
      patients with small PCs (P <= 0.04). Cutoffs for low- and high-grade risk scores
      implying the presence of small PC and all PC were 3P and 1P, respectively. When
      subjects having one or both cutoff scores were screened, sensitivity and
      specificity were 100% and 64.4% for small PCs and 95.5% and 64.4% for all PCs.
      CONCLUSION: Endoscopic ultrasonography screening combining new scoring is
      effective for detecting small PC.

PMID- 29329162
TI  - Reorganizing Care With the Implementation of Electronic Medical Records: A Time
      Motion Study in the PICU.
AB  - OBJECTIVES: To assess caregivers' patient care time before and after the
      implementation of a reorganization of care plan with electronic medical records.
      DESIGN: A prospective, observational, time-motion study. SETTING: A level 3 PICU.
      PARTICIPANTS: Nurses and orderlies caring for intubated patients during an 8-hour
      work shift before (2008-2009) and after (2016) implementation of reorganization
      of care in 2013. INTERVENTIONS: The reorganization plan included improved
      telecommunication for healthcare workers, increased tasks delegated to orderlies,
      and an ICU-specific electronic medical record (Intellispace Critical Care and
      Anesthesia information system, Philips Healthcare). MEASUREMENTS AND MAIN
      RESULTS: Time spent completing various work tasks was recorded by direct
      observation, and proportion of time in tasks was compared for each study period.
      A total of 153.7 hours was observed from 22 nurses and 14 orderlies. There was no
      significant difference in the proportion of nursing patient care time before
      (68.8% [interquartile range, 48-72%]) and after (55% [interquartile range, 51
      57%]) (p = 0.11) the reorganization with electronic medical record. Direct
      patient care task time for nurses was increased from 27.0% (interquartile range,
      30-37%) before to 34.7% (interquartile range, 33-75%) (p = 0.336) after, and
      indirect patient care tasks decreased from 33.6% (interquartile range, 23-41%) to
      18.6% (interquartile range, 16-22%) (p = 0.036). Documentation time significantly
      increased from 14.5% (interquartile range, 12-22%) to 26.2% (interquartile range,
      23-28%) (p = 0.032). Nursing productivity ratio improved from 28.3 to 26.0. A
      survey revealed that nursing staff was satisfied with the electronic medical
      record, although there was a concern for the maintenance of oral communication in
      the unit. CONCLUSIONS: The reorganization of care with the implementation of an
      ICU-specific electronic medical record in the PICU did not change total patient
      care provided but improved nursing productivity, resulting in improved
      efficiency. Documentation time was significantly increased, and concern over
      reduced oral communication arose, which should be a focus for future electronic
      improvement strategies.

PMID- 29329163
TI  - The Importance of Parental Connectedness and Relationships With Healthcare
      Professionals in End-of-Life Care in the PICU.
AB  - OBJECTIVES: Support from healthcare professionals in a PICU is highly valuable
      for parents of dying children. The way they care for the patients and their
      families affects the parents' initial mourning process. This study explores what
      interaction with hospital staff is meaningful to parents in existential distress
      when their child is dying in the PICU. DESIGN: Qualitative interview study.
      SETTING: Level 3 PICU in the Erasmus University Medical Center-Sophia Children's
      Hospital, Rotterdam, and the Netherlands. SUBJECTS: Thirty-six parents of 20
      children who had died in this unit 5 years previously. INTERVENTIONS: Parents
      participated in audio-recorded interviews in their own homes. The interviews were
      transcribed and analyzed using qualitative methods. MEASUREMENTS AND MAIN
      RESULTS: Parents' narratives of their child's end-of-life stage in the PICU
      bespeak experiences of estrangement, emotional distancing, and loneliness.
      Significant moments shared with hospital staff that remained valuable even after
      5 years primarily involved personal connectedness, reflected in frequent
      informational updates, personal commitment of professionals, and interpersonal
      contact with doctors and nurses. CONCLUSIONS: Parents whose children died in the
      PICU value personal connectedness to doctors and nurses when coping with
      existential distress. Medical and nursing training programs should raise
      awareness of parents' need for contact in all interactions but especially in
      times of crisis and apprehension.

PMID- 29329164
TI  - A Systematic Review of Risk Factors Associated With Cognitive Impairment After
      Pediatric Critical Illness.
AB  - OBJECTIVES: To identify risk factors associated with cognitive impairment as
      assessed by neuropsychologic tests in neurotypical children after critical
      illness. DATA SOURCES: For this systematic review, we searched the Cochrane
      Library, Scopus, PubMed, Ovid, Embase, and CINAHL databases from January 1960 to
      March 2017. STUDY SELECTION: Included were studies with subjects 3-18 years old
      at the time of post PICU follow-up evaluation and use of an objective
      standardized neuropsychologic test with at least one cognitive functioning
      dimension. Excluded were studies featuring patients with a history of cardiac
      arrest, traumatic brain injury, or genetic anomalies associated with
      neurocognitive impairment. DATA EXTRACTION: Twelve studies met the sampling
      criteria and were rated using the Newcastle-Ottawa Quality Assessment Scale. DATA
      SYNTHESIS: Ten studies reported significantly lower scores in at least one
      cognitive domain as compared to healthy controls or normed population data; seven
      of these-four case-control and three prospective cohort studies-reported
      significant lower scores in more than one cognitive domain. Risk factors
      associated with post critical illness cognitive impairment included younger age
      at critical illness and/or older age at follow-up, low socioeconomic status, high
      oxygen requirements, and use of mechanical ventilation, sedation, and pain
      medications. CONCLUSIONS: Identifying risk factors for poor cognitive outcomes
      post critical illness may help healthcare teams modify patient risk and/or
      provide follow-up services to improve long-term cognitive outcomes in high-risk
      children.

PMID- 29329165
TI  - Repeat Rapid Response Events in Children: Characteristics and Outcomes.
AB  - OBJECTIVE: We describe the characteristics and outcomes of pediatric repeat rapid
      response events within a single hospitalization. We hypothesized that triggers
      for repeat rapid response and initial rapid response events are similar, and
      repeat rapid response events are associated with high prevalence of medical
      complexity and worse outcomes. DESIGN: A 3-year retrospective study. SETTING:
      High-volume tertiary academic pediatric hospital. PATIENTS: All rapid response
      events were reviewed to identify repeat rapid response events. INTERVENTION:
      None. MEASUREMENTS AND MAIN RESULTS: Patient demographics, rapid response
      triggers, primary clinical diagnoses, illness acuity scores, medical
      interventions, transfers to ICU, occurrence of critical deterioration, and
      mortality were reviewed. We reviewed 146 patients with 309 rapid response events
      (146 initial rapid response and 163 repeat rapid response: 36% < 24 hr, 38% 24 hr
      to 7 d, and 26% > 7 d after initial rapid response). Median age was 3 years, and
      60% were males. Eighty-five percentage of repeat rapid response occurred in
      medical complexity patients. The triggers for 71% of all repeat rapid response
      matched with those of initial rapid response. Transfer to ICU occurred in 69
      (47%) of initial rapid response and 124 (76%) of repeat rapid response (p <
      0.01). The median hospital stay was 11 and 30 days for previously healthy and
      medical complexity patients, respectively (p = 0.16). ICU readmission at repeat
      rapid response was associated with longer hospital stay (p < 0.01). Mortality
      during hospitalization occurred in 14% (all medically complex) of patients after
      repeat rapid response. Hospital mortality after rapid response is 4.4% per our
      center's administrative data and 6.7% according to published multicenter data.
      CONCLUSIONS: Prevalence of medical complexity was high in patients with repeat
      rapid response compared with that reported for pediatric hospitalizations.
      Triggers between initial and repeat rapid response events correlated. Transfer to
      ICU was more likely after repeat rapid response and among repeat rapid response,
      events with ICU readmissions had a longer length of ICU and hospital stay.
      Mortality for the repeat rapid response cohort was higher than that for overall
      rapid responses in our center and per published reports from other centers.

PMID- 29329166
TI  - Hematologic Manifestations of Brucellosis in Children.
AB  - BACKGROUND: Brucellosis is a common zoonosis in the Bedouin population of
      southern Israel. Limited data exist for the rate and risk factors of hematologic
      complication of brucellosis in children. We assessed anemia, leukopenia,
      thrombocytopenia and pancytopenia in childhood brucellosis in southern Israel.
      METHODS: Our medical center is the sole hospital in southern Israel. All medical
      files of brucellosis, 2005-2014, identified through positive blood cultures or
      International Classification of Diseases 9th revision coding with positive
      serology, were reviewed retrospectively. RESULTS: Overall, 511 brucellosis
      episodes were identified; 42% (N = 214) with >=1 cytopenia, including 13% (N =
      68) anemia, 28% (N = 144) leukopenia, 14% (N = 74) thrombocytopenia and 2% (N =
      9) pancytopenia. Overall, 99.8% of episodes were in Bedouin children and 70% in
      males. In 79% of episodes, blood culture was positive for Brucella melitensis.
      Acute infections comprised 84% of all episodes. In univariate analysis, older age
      (10.49 +/- 4.81 vs. 9.25 +/- 4.89 years), fever (92% vs. 78%), positive blood
      culture (84% vs. 75%) and IgM >=1:640 levels (50% vs. 39%) were associated with
      cytopenia. In contrast, arthralgia was associated with noncytopenic episodes. In
      multivariate analyses, older age (odds ratio = 1.063) and fever (odds ratio =
      3.127) were associated with cytopenia. CONCLUSIONS: Brucellosis is commonly
      presented with cytopenia, especially in bacteremic episodes with fever. However,
      pancytopenia is uncommon and its finding should alert the physician to look for
      other possible etiologies.

PMID- 29329167
TI  - A Physician's Recommendation for Human Papillomavirus Vaccination: What Makes
      African-American Mothers Compliant?
AB  - BACKGROUND: Improving human papillomavirus (HPV) vaccination among African
      American (AA) female adolescents to reduce the cervical cancer burden is
      important and cost-effective. The study objective is to identify factors most
      influential to AA mothers' likelihood to comply with a physician's recommendation
      to get their daughters the HPV vaccine. METHODS: We conducted a cross-sectional
      survey. Participants were recruited through online and community sites (ie,
      schools, community centers, etc.) in Alabama. A total of 280 AA mothers and their
      adolescent daughters completed the survey. A binary logistic regression was used
      to determine factors influencing mother's likelihood to adhere with a physician's
      recommendation to get their daughters the HPV vaccine. RESULTS: The most
      significant factors influencing mother's likelihood to comply with physician's
      recommendation were culture: future-time orientation (P = 0.001), perceived
      barriers of HPV vaccination (P = 0.007), perceived susceptibility to HPV (P =
      0.047) and perceived benefits of HPV vaccination (P = 0.002). Further exploration
      of perceived barriers and perceived benefits found mother's perception that the
      HPV vaccine is a good way to protect my daughter's health as the only significant
      benefit. No measures of perceived barriers were significant. CONCLUSIONS: A
      physician's recommendation should advise AA mothers on the risk of HPV and the
      importance of HPV vaccination at an early age to reduce cervical cancer risk. It
      should further address mothers' perceived disadvantages of HPV vaccination (eg,
      side effects). Incorporating this information in physician recommendation
      practices could increase HPV vaccination rates with implications in reducing the
      cervical cancer burden among this high-risk population.

PMID- 29329168
TI  - Immune Responses to Booster Vaccination With Meningococcal ABCWY Vaccine After
      Primary Vaccination With Either Investigational or Licensed Vaccines: A Phase 2
      Randomized Study.
AB  - BACKGROUND: Current meningococcal prime-boost vaccination schedules include
      separate vaccines for serogroups ACWY and B. An investigational combined
      serogroups ABCWY vaccine (MenABCWY) was developed to protect against clinically
      important Neisseria meningitidis serogroups. METHODS: In this phase 2,
      randomized, observer-blind, extension study (NCT01272180), participants 10-25
      years of age received 1 booster dose of MenABCWY vaccine at 24 months (M)
      postprimary series of MenABCWY (2 doses), 4CMenB (2 doses) or MenACWY-CRM vaccine
      (1 dose). Immune responses to booster dose (1M postbooster) and antibody
      persistence (24M, 36M postprimary series) were assessed using bactericidal assay
      with human complement (hSBA). Reactogenicity and safety were evaluated. RESULTS:
      One hundred ninety participants were vaccinated. At 1M after the MenABCWY booster
      dose, seroresponse rates against serogroups ACWY ranged between 85% and 96%, 73%
      and 100% and 83% and 95% for participants previously receiving MenABCWY, 4CMenB
      and MenACWY-CRM, respectively. At 12M postbooster dose, >=67% of participants
      across all groups had hSBA titers >=8 for serogroups ACWY, except in 4CMenB
      primed individuals for serogroup Y (45%). Across MenABCWY and 4CMenB-primed
      groups, hSBA titers >=5 across serogroup B test strains were observed in 82%-100%
      and 29%-100% of participants at 1M and 12M postbooster, respectively. Geometric
      mean titers against serogroups ACWY increased from pre- to 1M postboosting with
      MenABCWY and persisted at 12M. The reactogenicity and safety profile of MenABCWY
      was similar to that of 4CMenB. CONCLUSIONS: MenABCWY may be suitable for prime
      boost schedules against meningococcal disease, including regimens involving a
      primary series of either 4CMenB or MenACWY-CRM licensed vaccines.

PMID- 29329169
TI  - Differences in Immunization Site Pain in Toddlers Vaccinated With Either the 10-
      or the 13-Valent Pneumococcal Conjugate Vaccine.
AB  - BACKGROUND: Immunization site pain is a common and unpleasant experience for both
      children and adults. It is a source of anxiety and distress and may ultimately
      result in nonadherence to vaccination schedules. There is limited information on
      how different brands of vaccines affect the intensity of immediate pain at the
      time of vaccine injection. METHODS: Children in the United Kingdom (n = 178) were
      randomized to receive a booster dose of either the 10- or the 13-valent
      pneumococcal conjugate vaccine (PCV-10 or PCV-13). Immediate immunization site
      pain was assessed using validated pain assessment tools and crying time to
      investigate factors that may interfere with parental compliance to vaccination.
      RESULTS: Pain measurements were available for n >= 74 and n >= 78 PCV-10 and PCV
      13 recipients, respectively. PCV-13 recipients had significantly higher scores on
      the observer-rated modified behavioral pain scale than did those receiving PCV
      10. No significant differences in the induction of pain between the 2 vaccines
      were found when a parent-rated pain assessment tool or crying time was used.
      CONCLUSIONS: PCV-10 administration was associated with slightly less acute pain
      compared with the injection of PCV-13, but the size of the difference was small
      and is of unknown clinical significance.

PMID- 29329170
TI  - What's New in Shock, February 2018?

PMID- 29329171
TI  - Nonhuman Primate (Rhesus Macaque) Models of Severe Pressure-Targeted Hemorrhagic
      and Polytraumatic Hemorrhagic Shock.
AB  - BACKGROUND: We endeavored to develop clinically translatable nonhuman primate
      (NHP) models of severe polytraumatic hemorrhagic shock. METHODS: NHPs were
      randomized into five severe pressure-targeted hemorrhagic shock (PTHS) +/-
      additional injuries scenarios: 30-min PTHS (PTHS-30), 60-min PTHS (PTHS-60), PTHS
      60 + soft tissue injury (PTHS-60+ST), PTHS-60+ST + femur fracture (PTHS
      60+ST+FF), and decompensated PTHS+ST+FF (PTHS-D). Physiologic parameters were
      recorded and blood samples collected at five time points with animal observation
      through T = 24 h. Results presented as mean +/- SEM; statistics: log
      transformation followed by two-way ANOVA with Bonferroni multiple comparisons,
      Wilcoxon nonparametric test for comparisons, and the Friedmans' one-way ANOVA;
      significance: P < 0.05. RESULTS: Percent blood loss was 40% +/- 2, 59% +/- 3, 52%
      +/- 3, 49% +/- 2, and 54% +/- 2 for PTHS-30, PTHS-60, PTHS-60+ST, PTHS-60+ST+FF,
      and PTHS-D, respectively. All animals survived to T = 24 h except one in each of
      the PTHS-60 and PTHS-60+ST+FF groups and seven in the PTHS-D group. Physiologic,
      coagulation, and inflammatory parameters demonstrated increasing derangements
      with increasing model severity. CONCLUSION: NHPs exhibit a high degree of
      resilience to hemorrhagic shock and polytrauma as evidenced by moderate
      perturbations in metabolic, coagulation, and immunologic outcomes with up to 60
      min of profound hypotension regardless of injury pattern. Extending the duration
      of PTHS to the point of decompensation in combination with polytraumatic injury,
      evoked derangements consistent with those observed in severely injured trauma
      patients which would require ICU care. Thus, we have successfully established a
      clinically translatable NHP trauma model for use in testing therapeutic
      interventions to trauma.

PMID- 29329172
TI  - Clinical Features and Outcomes of Post-Traumatic Silent Sinus Syndrome.
AB  - PURPOSE: To identify demographic features and clinical outcomes associated with
      post-traumatic silent sinus syndrome. METHODS: A retrospective review was carried
      out at 3 academic medical centers to identify all cases of post-traumatic silent
      sinus syndrome. Clinical features and management strategies were recorded.
      Postoperative outcomes were assessed, and statistical analyses were performed via
      a dedicated computerized software package. RESULTS: Twenty cases were identified
      (14 men and 6 women, mean age = 44.2 years). Seven patients underwent sinus
      surgery as the sole means of treatment, and the mean pre- and postoperative
      enophthalmos measurements were 2.86 and 1.93 mm. Alternatively, 13 patients
      underwent combined orbital reconstruction and sinus surgery, respectively; the
      mean pre- and postoperative enophthalmos measurements were 3.42 and 0.39 mm,
      respectively. The change in enophthalmos was statistically significantly greater
      in patients who underwent sinus surgery and orbital reconstruction (p = 0.00028).
      Among patients who underwent sinus surgery alone, one patients (14.2%)
      experienced complete resolution of enophthalmos, as compared with 10 patients
      (76.9%) who underwent combined procedures. CONCLUSIONS: This study represents the
      largest published cohort of patients with post-traumatic silent sinus syndrome.
      Combined orbital reconstruction and sinus surgery results in greater reductions
      of enophthalmos and a markedly improved chance of postoperative symmetry of globe
      position.

PMID- 29329173
TI  - Continuous Positive Airway Pressure Thresholds for Nasolacrimal Air Regurgitation
      in a Cadaveric Model.
AB  - PURPOSE: To elucidate the mechanisms underlying nasolacrimal air regurgitation
      (AR) in the setting of continuous positive airway pressure therapy. METHODS:
      Twelve nasolacrimal systems of 6 fresh female human cadavers were evaluated
      individually for AR using continuous positive airway pressure therapy before any
      nasolacrimal procedure. Cadavers were then randomly assigned to undergo
      nasolacrimal duct probing or endoscopic dacryocystorhinostomy and then each
      hemisystem was again evaluated for AR. The pressure where AR was first observed
      (discovery pressure) or maximum possible pressure in systems without AR was
      recorded. In systems that demonstrated AR, the pressure was then gradually
      decreased to the lowest pressure where regurgitation persisted. This pressure was
      recorded as the secondary threshold pressure. RESULTS: None of the 12 unoperated
      nasolacrimal systems or the 6 systems that underwent nasolacrimal duct probing
      demonstrated AR through the maximum continuous positive airway pressure therapy
      (30 cm H2O). After endoscopic dacryocystorhinostomy, all 6 nasolacrimal systems
      demonstrated AR. The mean discovery pressure was 16.0 cm H2O (range, 14.0-18.0 cm
      H2O) and mean secondary threshold pressure was 7.25 cm H2O (range, 6.5-8.0 cm
      H2O). CONCLUSIONS: Air regurgitation during continuous positive airway pressure
      therapy in the setting of prior endoscopic dacryocystorhinostomy can be
      replicated in a cadaver model. The secondary threshold pressures required for AR
      in this model were similar to AR pressures reported clinically. Prior to
      dacryocystorhinostomy, patients using continuous positive airway pressure therapy
      should be counseled on AR, and physicians should consider this phenomenon when
      evaluating ophthalmic complaints in postoperative patients on positive airway
      pressure therapy.

PMID- 29329174
TI  - Symmetry of Upper Eyelid Contour After Unilateral Blepharoptosis Repair With a
      Single-strip Frontalis Suspension Technique.
AB  - PURPOSE: To analyze the upper eyelid contour of patients with unilateral
      congenital ptosis who underwent single-strip frontalis suspension. METHODS: The
      authors compared the upper eyelid shape of the right and left eyes of 10 patients
      who underwent unilateral frontalis suspension with a single strip of autogenous
      fascia. At a mean postoperative time of 10.1 +/- 4.01 months, the image J
      software was used to measure the ratio between the nasal and temporal areas of
      the upper half of the palpebral fissure. The midpupil upper eyelid distance
      (MRD1) was also measured on the photos with the same software. The nonparametric
      Wilcoxon signed-rank test was used to compare the data. RESULTS: Postoperative
      MRD1 ranged from 2.5 to 4.7 mm (median = 3.8) on the affected side. The MRD1 for
      nonoperated eyelid ranged from 1.8 to 5.0 mm (median = 3.5). On the operated
      side, the temporal areas ranged from 50.3 to 85.7 mm (median 65.2) and nasal
      areas ranged from 41.5 to 72.3 (the median was 60.1). In the contralateral,
      nonoperated palpebral fissures, the temporal areas ranged from 42.7 to 94.3 mm
      (median = 54.5) and the nasal areas ranged from 36.8 to 86.1 mm (median 52.3).
      The T/N ratio distributions were almost identical between groups, ranging from
      0.9 to 1.2 (median = 1.1) in the operated eyes and from 0.9 to 1.3 (median = 1.1)
      in the fellow eyes. CONCLUSIONS: In autogenous fascia frontalis suspension
      procedures, the upper eyelid contour of the ptotic eyelids can be adequately
      normalized with a single area of traction on the tarsal plate.

PMID- 29329176
TI  - A Cost Analysis of Gyrase A Testing and Targeted Ciprofloxacin Therapy Versus
      Recommended 2-Drug Therapy for Neisseria gonorrhoeae Infection.
AB  - BACKGROUND: Novel approaches to combating drug-resistant Neisseria gonorrhoeae
      infections are urgently needed. Targeted therapy with ciprofloxacin has been made
      possible by a rapid assay for genotyping the gyrase A (gyrA) gene; a nonmutated
      gene reliably predicts susceptibility to ciprofloxacin. METHODS: We determined
      the costs of running the gyrA assay, 500 mg of ciprofloxacin, 250 mg of
      ceftriaxone injection, and 1000 mg of azithromycin. Cost estimates for gyrA
      testing included assay reagents and labor. Cost estimates for ceftriaxone
      included medication, injection, administration, supplies, and equipment. We
      measured the cost of using the gyrA assay and treatment based on genotype using
      previously collected data over a 13-month period between November 2015 and
      November 2016 for all N. gonorrhoeae cases diagnosed at UCLA. We subsequently
      developed 3 cost models, varying the frequency of testing and prevalence of N.
      gonorrhoeae infections with ciprofloxacin-resistant or genotype-indeterminate
      results. We compared those estimates with the cost of recommended 2-drug therapy
      (ceftriaxone and azithromycin). RESULTS: Based on a 65.3% prevalence of cases
      with ciprofloxacin-resistant or genotype indeterminate N. gonorrhoeae infections
      when running an average of 1.7 tests per day, the per-case cost of gyrA
      genotyping and targeted therapy was US $197.19. The per-case cost was US $155.16
      assuming a 52.6% prevalence of ciprofloxacin-resistant or genotype-indeterminate
      infections when running an average of 17 tests per day. The per-case cost of 2
      drug therapy was US $142.75. CONCLUSIONS: Direct costs of gyrA genotyping and
      targeted ciprofloxacin therapy depend on the prevalence of ciprofloxacin
      resistant or genotype-indeterminate infections and testing frequency.

PMID- 29329177
TI  - A Comparison of Real-Time Polymerase Chain Reaction Assays for the Detection of
      Antimicrobial Resistance Markers and Sequence Typing From Clinical Nucleic Acid
      Amplification Test Samples and Matched Neisseria gonorrhoeae Culture.
AB  - Real-time polymerase chain reaction (PCR) assays to detect antimicrobial
      resistance-associated mutations were tested on Neisseria gonorrhoeae-positive
      clinical samples with matched isolates. Of the nucleic acid amplification
      tests/cultures, 87.7% (64/73), 98.6% (72/73), and 98.4% (62/63) predicted
      cephalosporin, ciprofloxacin, and azithromycin susceptibilities, respectively. N.
      gonorrhoeae multiantigen sequence type was correctly predicted for 98.7% (79/80),
      and 13 of 58 N. gonorrhoeae-negative specimens showed false-positive results.

PMID- 29329178
TI  - Chlamydia and Gonorrhea Acquisition Among Adolescents and Young Adults in
      Pennsylvania: A Rural and Urban Comparison.
AB  - Adolescent and young adult chlamydia and gonorrhea rates in rural versus urban
      communities of Pennsylvania were analyzed from 2004 to 2014. Higher rates of
      chlamydia and gonorrhea have been documented in rural youth, making them more
      likely to acquire to suffer adverse outcomes than youth in urban populations.

PMID- 29329175
TI  - Clinical Description, Molecular Analysis of TWIST2 Gene, and Surgical Treatment
      in a Patient With Barber-Say Syndrome.
AB  - Barber-Say syndrome is a rare autosomal dominant disease characterized by
      dysmorphic features, mainly of the eyelids and skin. It is caused by heterozygous
      mutations in gene TWIST2, localized in chromosome 2q37.3. The authors present the
      case of a pediatric patient with a clinical diagnosis of Barber-Say syndrome with
      ocular symptoms related to exposure keratitis. Molecular analysis of her DNA
      revealed a mutation on TWIST2 gene confirming the diagnosis of Barber-Say
      syndrome. Surgical treatment of the patient's eyelids resolved her signs and
      symptoms.

PMID- 29329179
TI  - Should Asymptomatic Men Who Have Sex With Men Be Screened for Oropharyngeal
      Chlamydia? Clinical Outcomes From a Cross-Sectional Study.
AB  - OBJECTIVE: To help inform screening guidelines, we estimated the proportion of
      asymptomatic men who have sex with men (MSM) with oropharyngeal chlamydia. STUDY
      DESIGN: An audit of asymptomatic MSM attending a sexual health service from March
      2015 to April 2016 was conducted. They each had an oropharyngeal swab that was
      tested for Chlamydia trachomatis by transcription-mediated nucleic acid
      amplification. In addition, a random sample of 17 swabs that initially tested
      positive had confirmatory testing to determine the likelihood of true positivity.
      RESULTS: We collected 4877 oropharyngeal swabs: 72 (1.5%; 95% confidence interval
      [CI], 1.2-1.9) were diagnosed positive for chlamydia. Most (n = 56 [78%]; 95% CI,
      67-86) only had oropharyngeal chlamydia detected (i.e., no concurrent
      extraoropharyngeal chlamydia and/or gonorrhea). Of the 17 samples that underwent
      confirmation, all confirmed positive (100%; 95% CI, 82-100). CONCLUSIONS:
      Although oropharyngeal chlamydia prevalence was low among asymptomatic MSM, most
      oropharyngeal chlamydia cases had no chlamydia at other sites, and these cases
      would have been missed and not treated if routine oropharyngeal chlamydia testing
      was not done.

PMID- 29329180
TI  - Diplopia: An Overlooked Feature in Patients With Neurosyphilis. Report of 2 Cases
      and Literature Review.
AB  - Both neurosyphilis and diplopia are widely known medical terms. Nevertheless, low
      clinical awareness by the physician and the often-overlooked presentation of
      diplopia, make the combination of neurosyphilis and diplopia rarely observed. In
      this article, we report 2 neurosyphilitic patients presenting with diplopia and
      review 8 additional case reports of neurosyphilis with diplopia, with a total of
      10 cases to be analyzed.

PMID- 29329181
TI  - What Is the Optimal Time to Retest Patients With a Urogenital Chlamydia
      Infection? A Randomized Controlled Trial.
AB  - BACKGROUND: Chlamydia trachomatis is a common, often recurring sexually
      transmitted infection, with serious adverse outcomes in women. Current guidelines
      recommend retesting after a chlamydia infection, but the optimum timing is
      unknown. We assessed the optimal retest interval after urogenital chlamydia
      treatment. METHODS: A randomized controlled trial among urogenital chlamydia
      nucleic acid amplification test positive heterosexual clients of the Amsterdam
      sexually transmitted infection clinic. After treatment, patients were randomly
      assigned for retesting 8, 16, or 26 weeks later. Patients could choose to do this
      at home (and send a self-collected sample by mail) or at the clinic. Retest
      uptake and chlamydia positivity at follow-up were calculated. RESULTS: Between
      May 2012 and March 2013, 2253 patients were included (45% men; median age, 23
      years; interquartile range, 21-26). The overall uptake proportion within 35 weeks
      after the initial visit was significantly higher in the 8-week group (77%)
      compared with the 16- and 26-week groups (67% and 64%, respectively, P < 0.001),
      and the positivity proportions among those retested were comparable (P = 0.169).
      The proportion of people with a diagnosed recurrent chlamydia infection among all
      randomized was similar between the groups (n = 69 [8.6%], n = 52 [7.4%], and n =
      69 [9.3%]; P = 0.4). CONCLUSIONS: Patients with a recent urogenital chlamydia are
      at high risk of recurrence of chlamydia and retesting them is an effective way of
      detecting chlamydia cases. We recommend inviting patients for a re-test 8 weeks
      after the initial diagnosis and treatment.

PMID- 29329182
TI  - Rapid Increase in Gonorrhea Cases With Reduced Susceptibility to Azithromycin in
      Columbus, Ohio.

PMID- 29329183
TI  - Hepatitis E Virus Infection in Kidney Transplant Patients: A Single-Center Study.

PMID- 29329184
TI  - Listening to Living Donors.

PMID- 29329186
TI  - High-Sensitivity Troponins in Liver Transplantation: How Will They Change Our
      Practice?

PMID- 29329185
TI  - Vasodilation During Normothermic Machine Perfusion; Preventing the No-Reflow
      Phenomena.

PMID- 29329187
TI  - Deceased Donor Organ Transplantation Performed in the United States for
      Noncitizens and Nonresidents.
AB  - Since 2012, the Organ Procurement and Transplantation Network (OPTN)/United
      Network for Organ Sharing (UNOS) has required transplant centers to record the
      citizenship residency status of patients undergoing transplantation in the United
      States. This policy replaced the 5% threshold of the non-US citizen/nonresidents
      (NC/NR) undergoing organ transplantation that could result in an audit of
      transplant center activity. Since April 1, 2015, the country of residence for the
      NC/NR on the waitlist has also been recorded. We analyzed the frequency of NC/NR
      deceased donor organ transplants and waitlist registrations at all US transplant
      centers by data provided by UNOS for that purpose to the UNOS Ad Hoc
      International Relations Committee. During the period of 2013 to 2016, 1176
      deceased donor transplants (of all organs) were performed in non-US citizen/non
      US resident (NC/NR) candidates (0.54% of the total number of transplants). We
      focused on high-volume NC/NR transplant centers that performed more than 5% of
      the deceased donor kidney or liver transplants in NC/NR or whose waitlist
      registrants exceeded 5% NC/NR. This report was prepared to fulfill the
      transparency policy of UNOS to assure a public trust in the distribution of
      organs. When viewed with a public awareness of deceased donor organ shortages, it
      suggests the need for a more comprehensive understanding of current NC/NR
      activity in the United States. Patterns of organ specific NC/NR registrations and
      transplantations at high-volume centers should prompt a review of transplant
      center practices to determine whether the deceased donor and center resources may
      be compromised for their US patients.

PMID- 29329188
TI  - The Impact of Combined Warm Ischemia Time on Development of Acute Kidney Injury
      in Donation After Circulatory Death Liver Transplantation: Stay Within the Golden
      Hour.
AB  - BACKGROUND: Acute kidney injury (AKI) is a common complication after liver
      transplantation and more frequently observed when high-risk grafts, such as
      donation after circulatory death (DCD) grafts are used. Our aim was to
      investigate the impact of the ischemia periods on development of AKI in DCD liver
      transplantation. METHODS: We performed a 2-center retrospective study with 368
      DCD graft-recipients. Donor warm ischemia time (DWIT) was divided into agonal
      phase (withdrawal of life support-cardiac arrest) and asystolic phase (cardiac
      arrest-start cold perfusion). We introduced a new period of warm ischemia: the
      combined warm ischemia time (combined WIT), which was defined as the sum of DWIT
      and recipient WIT. RESULTS: AKI was observed in 65% of the recipients and severe
      AKI in 41% (KDIGO stage 2/3). The length of combined WIT increased significantly
      with AKI severity: 61 minutes in recipients without AKI up to 69 minutes in
      recipients with the most severe form of AKI (P < 0.001). On multivariable
      analysis, increasing duration of the combined WIT was associated with an
      increased risk of developing severe AKI (odds ratio, 1.032 per every extra
      minute; 95% confidence interval, 1.014-1.051; P < 0.001). No relation was
      observed between length of cold ischemia time and severe AKI. CONCLUSIONS:
      Combined WIT is a newly defined period of warm ischemia in DCD liver
      transplantation. Length of combined WIT is associated with severity of
      postoperative AKI and should ideally not exceed 60 minutes.

PMID- 29329189
TI  - Beta Cell Death by Cell-free DNA and Outcome After Clinical Islet
      Transplantation.
AB  - BACKGROUND: Optimizing engraftment and early survival after clinical islet
      transplantation is critical to long-term function, but there are no reliable,
      quantifiable measures to assess beta cell death. Circulating cell-free DNA
      (cfDNA) derived from beta cells has been identified as a novel biomarker to
      detect cell loss and was recently validated in new-onset type 1 diabetes and in
      islet transplant patients. METHODS: Herein we report beta cell cfDNA measurements
      after allotransplantation in 37 subjects and the correlation with clinical
      outcomes. RESULTS: A distinctive peak of cfDNA was observed 1 hour after
      transplantation in 31 (83.8%) of 37 subjects. The presence and magnitude of this
      signal did not correlate with transplant outcome. The 1-hour signal represents
      dead beta cells carried over into the recipient after islet isolation and
      culture, combined with acute cell death post infusion. Beta cell cfDNA was also
      detected 24 hours posttransplant (8/37 subjects, 21.6%). This signal was
      associated with higher 1-month insulin requirements (P = 0.04), lower 1-month
      stimulated C-peptide levels (P = 0.01), and overall worse 3-month engraftment, by
      insulin independence (receiver operating characteristic-area under the curve =
      0.70, P = 0.03) and beta 2 score (receiver operating characteristic-area under
      the curve = 0.77, P = 0.006). CONCLUSIONS: cfDNA-based estimation of beta cell
      death 24 hours after islet allotransplantation correlates with clinical outcome
      and could predict early engraftment.

PMID- 29329191
TI  - Income Disparities in the Prevalence, Severity, and Costs of Co-occurring Chronic
      and Behavioral Health Conditions.
AB  - BACKGROUND: Behavioral health problems usually co-occur along with physical
      health problems, resulting in higher health care costs. These co-occurring
      conditions are likely to be more prevalent and serious among low income patients,
      affecting both the quality and costs of care. OBJECTIVE: To examine the
      prevalence, severity, and health care costs of co-occurring chronic and
      behavioral health conditions among low income people compared with higher income
      people. METHODS: Analysis of the 2011-2014 Medical Expenditure Panel Survey.
      Sample includes 146,000 persons aged 18-64 years. Regression analysis was used to
      examine how the combination of behavioral health conditions and chronic health
      conditions is associated with health care expenditures, and how this association
      differs by family income. RESULTS: (1) Comorbid behavioral health problems are
      more prevalent and serious among low income people with chronic conditions
      compared with higher income people; (2) among patients with co-occurring chronic
      and behavioral problems, average annual spending is greater among the low income
      patients ($9472) compared with high income patients ($7457); (3) higher costs
      among low income patients with co-occurring conditions reflects their poorer
      mental and physical health, relative to higher income patients. CONCLUSIONS: For
      many low income people, comorbid behavioral problems need to be understood in the
      social context in which they live. Simply screening low income people for
      behavioral health problems may not be sufficient unless there is greater
      understanding of the mechanisms that both cause and exacerbate chronic and
      behavioral health problems in the low income population.

PMID- 29329193
TI  - Mustn1: A Developmentally Regulated Pan-Musculoskeletal Cell Marker and
      Regulatory Gene.
AB  - The Mustn1 gene encodes a small nuclear protein (~9.6 kDa) that does not belong
      to any known family. Its genomic organization consists of three exons
      interspersed by two introns and it is highly homologous across vertebrate
      species. Promoter analyses revealed that its expression is regulated by the AP
      family of transcription factors, especially c-Fos, Fra-2 and JunD. Mustn1 is
      predominantly expressed in the major tissues of the musculoskeletal system: bone,
      cartilage, skeletal muscle and tendon. Its expression has been associated with
      normal embryonic development, postnatal growth, exercise, and regeneration of
      bone and skeletal muscle. Moreover, its expression has also been detected in
      various musculoskeletal pathologies, including arthritis, Duchenne muscular
      dystrophy, other skeletal muscle myopathies, clubfoot and diabetes associated
      muscle pathology. In vitro and in vivo functional perturbation revealed that
      Mustn1 is a key regulatory molecule in myogenic and chondrogenic lineages. This
      comprehensive review summarizes our current knowledge of Mustn1 and proposes that
      it is a new developmentally regulated pan-musculoskeletal marker as well as a key
      regulatory protein for cell differentiation and tissue growth.

PMID- 29329195
TI  - Dietary Antioxidants and Health Promotion.
AB  - Accumulating scientific evidence suggests that over-production of reactive oxygen
      species (ROS) may be the root cause of chronic diseases such as cancer,
      cardiovascular diseases, neurodegeneration, and ageing per se [1,2].[...].

PMID- 29329196
TI  - Is the Skin Absorption of Hydrocortisone Modified by the Variability in Dosing
      Topical Products?
AB  - Fingertip units have been proposed as a tool to standardize topical therapy with
      semisolid formulations. However, no studies to date have characterized the
      variability in dosing by patients using this concept and whether this variability
      ultimately affects the topical absorption of drugs. This work aimed to answer
      these two questions. A first study determined the dose measured, the area of
      spread and the area-normalized dose for a 1% hydrocortisone cream and ointment
      applied by members of the public using this dosing approach before and after
      brief counselling. Then, in vivo tape-stripping and in vitro permeation studies
      investigated whether the variability in the area-normalized dose altered the skin
      absorption of hydrocortisone. Participants applied greater doses and spread them
      over larger areas after a short counselling intervention leading to smaller area
      normalized doses. In vivo hydrocortisone uptake by the stratum corneum was
      significantly greater for the higher normalized dose and the differences were
      further supported by the in vitro permeation studies. However, these differences
      were relatively small and not proportional to the increase in normalized dose.
      This work shows that, following brief advice, patients and carers can apply
      consistent and sufficient doses of corticosteroids whilst minimizing risks and
      variability in hydrocortisone absorption.

PMID- 29329197
TI  - Long-Term Functional Outcome of Surgical Treatment for Thoracic Outlet Syndrome.
AB  - First rib resection for thoracic outlet syndrome (TOS) is clinically successful
      and safe in most patients. However, long-term functional outcomes are still
      insufficiently known. Long-term functional outcome was assessed using a validated
      questionnaire. A multicenter retrospective cohort study including all patients
      who underwent operations for TOS from January 2005 until December 2016. Clinical
      records were reviewed and the long-term functional outcome was assessed by the 11
      item version of the Disability of the Arm, Shoulder, and Hand (QuickDASH)
      questionnaire. Sixty-two cases of TOS in 56 patients were analyzed: 36 neurogenic
      TOS, 13 arterial TOS, 7 venous TOS, and 6 combined TOS. There was no 30-day
      mortality. One reoperation because of bleeding was performed and five patients
      developed a pneumothorax. Survey response was 73% (n = 41) with a follow-up
      ranging from 1 to 11 years. Complete relief of symptoms was reported
      postoperatively in 27 patients (54%), symptoms improved in 90%, and the mean
      QuickDASH score was 22 (range, 0-86). Long-term functional outcome of surgical
      treatment of TOS was satisfactory, and surgery was beneficial in 90% of patients,
      with a low risk of severe morbidity. However, the mean QuickDASH scores remain
      higher compared with the general population, suggesting some sustained functional
      impairment despite clinical improvement of symptoms.

PMID- 29329199
TI  - Pressure Induced Densification and Compression in a Reprocessed Borosilicate
      Glass.
AB  - Pressure induced densification and compression of a reprocessed sample of
      borosilicate glass has been studied by X-ray radiography and energy dispersive X
      ray diffraction using a Paris-Edinburgh (PE) press at a synchrotron X-ray source.
      The reprocessing of a commercial borosilicate glass was carried out by cyclical
      melting and cooling. Gold foil pressure markers were used to obtain the sample
      pressure by X-ray diffraction using its known equation of state, while X-ray
      radiography provided a direct measure of the sample volume at high pressure. The
      X-ray radiography method for volume measurements at high pressures was validated
      for a known sample of pure alpha-Iron to 6.3 GPa. A sample of reprocessed
      borosilicate glass was compressed to 11.4 GPa using the PE cell, and the
      flotation density of pressure recovered sample was measured to be 2.755 gm/cc,
      showing an increase in density of 24%, as compared to the starting sample. The
      initial compression of the reprocessed borosilicate glass measured by X-ray
      radiography resulted in a bulk modulus of 30.3 GPa in good agreement with the
      32.9 GPa value derived from the known elastic constants. This method can be
      applied to variety of amorphous materials under high pressures.

PMID- 29329201
TI  - Population Reference Values for Serum Methylmalonic Acid Concentrations and Its
      Relationship with Age, Sex, Race-Ethnicity, Supplement Use, Kidney Function and
      Serum Vitamin B12 in the Post-Folic Acid Fortification Period.
AB  - Serum methylmalonic acid (MMA) is elevated in vitamin B-12 deficiency and in
      kidney dysfunction. Population reference values for serum MMA concentrations in
      post-folic acid fortification period are lacking. Aims of this study were to
      report the population reference values for serum MMA and to evaluate the relation
      between serum MMA and sex, age, race-ethnicity, kidney dysfunction and vitamin B
      12. We used data from three National Health and Nutrition Examination Surveys,
      1999-2000, 2001-2002 and 2003-2004 conducted after folic acid fortification
      commenced (n = 18,569). Geometric mean MMA was ~22.3% higher in non-Hispanic
      white compared to non-Hispanic black (141.2 vs. 115.5 nmol/L) and was ~62.7%
      higher in >70 years old persons compared to 21-30 years old persons (196.9 vs.
      121.0 nmol/L). Median serum MMA was ~28.5% higher in the 1st the quartile of
      serum vitamin B-12 than in the 4th quartile of serum vitamin B-12 and was ~35.8%
      higher in the 4th quartile of serum creatinine than in the 1st quartile of serum
      creatinine. Multivariate-adjusted serum MMA concentration was significantly
      associated with race-ethnicity (p < 0.001) and age (p < 0.001) but not with sex
      (p = 0.057). In this large US population based study, serum MMA concentrations
      presented here reflect the post-folic acid fortification scenario. Serum MMA
      concentrations begin to rise at the age of 18-20 years and continue to rise
      afterwards. Age-related increase in serum MMA concentration is likely to be due
      to a concomitant decline in kidney function and vitamin B-12 status.

PMID- 29329203
TI  - Thermoelectric Mixed Thick-/Thin Film Microgenerators Based on Constantan/Silver.
AB  - This paper describes the design, manufacturing and characterization of newly
      developed mixed thick-/thin film thermoelectric microgenerators based on
      magnetron sputtered constantan (copper-nickel alloy) and screen-printed silver
      layers. The thermoelectric microgenerator consists of sixteen thermocouples made
      on a 34.2 * 27.5 * 0.25 mm3 alumina substrate. One of thermocouple arms was made
      of magnetron-sputtered constantan (Cu-Ni alloy), the second was a Ag-based screen
      printed film. The length of each thermocouple arm was equal to 27 mm, and their
      width 0.3 mm. The distance between the arms was equal to 0.3 mm. In the first
      step, a pattern mask with thermocouples was designed and fabricated. Then, a
      constantan layer was magnetron sputtered over the whole substrate, and a
      photolithography process was used to prepare the first thermocouple arms. The
      second arms were screen-printed onto the substrate using a low-temperature silver
      paste (Heraeus C8829A or ElectroScience Laboratories ESL 599-E). To avoid
      oxidation of constantan, they were fired in a belt furnace in a nitrogen
      atmosphere at 550/450  degrees C peak firing temperature. Thermoelectric and
      electrical measurements were performed using the self-made measuring system. Two
      pyrometers included into the system were used for temperature measurement of hot
      and cold junctions. The estimated Seebeck coefficient, alpha was from the range
      35 - 41 uV/K, whereas the total internal resistances R were between 250 and 3200
      ohms, depending on magnetron sputtering time and kind of silver ink (the
      resistance of a single thermocouple was between 15.5 and 200 ohms).

PMID- 29329205
TI  - Improving Odometric Accuracy for an Autonomous Electric Cart.
AB  - In this paper, a study of the odometric system for the autonomous cart Verdino,
      which is an electric vehicle based on a golf cart, is presented. A mathematical
      model of the odometric system is derived from cart movement equations, and is
      used to compute the vehicle position and orientation. The inputs of the system
      are the odometry encoders, and the model uses the wheels diameter and distance
      between wheels as parameters. With this model, a least square minimization is
      made in order to get the nominal best parameters. This model is updated,
      including a real time wheel diameter measurement improving the accuracy of the
      results. A neural network model is used in order to learn the odometric model
      from data. Tests are made using this neural network in several configurations and
      the results are compared to the mathematical model, showing that the neural
      network can outperform the first proposed model.

PMID- 29329202
TI  - EpCAM Immunotherapy versus Specific Targeted Delivery of Drugs.
AB  - The epithelial cell adhesion molecule (EpCAM), or CD326, was one of the first
      cancer associated biomarkers to be discovered. In the last forty years, this
      biomarker has been investigated for use in personalized cancer therapy, with the
      first monoclonal antibody, edrecolomab, being trialled in humans more than thirty
      years ago. Since then, several other monoclonal antibodies have been raised to
      EpCAM and tested in clinical trials. However, while monoclonal antibody therapy
      has been investigated against EpCAM for almost 40 years as primary or adjuvant
      therapy, it has not shown as much promise as initially heralded. In this review,
      we look at the reasons why and consider alternative targeting options, such as
      aptamers, to turn this almost ubiquitously expressed epithelial cancer biomarker
      into a viable target for future personalized therapy.

PMID- 29329204
TI  - Lipid-Lowering Polyketides from the Fungus Penicillium Steckii HDN13-279.
AB  - Seven new polyketides, named tanzawaic acids R-X (1-6, 11), along with seven
      known analogues (7-10 and 12-14), were isolated from Penicillium steckii HDN13
      279. Their structures, including the absolute configurations, were elucidated by
      NMR, MS, X-ray diffraction, circular dichroism (CD) analyses and chemical
      derivatization. Five compounds (2, 3, 6, 10 and 12) significantly decreased the
      oleic acid (OA)-elicited lipid accumulation in HepG2 liver cells at the
      concentration of 10 MUM, among which, four compounds (3, 6, 10 and 12)
      significantly decreased intracellular total cholesterol (TC) levels and three
      Compounds (3, 6, and 10) significantly decreased intracellular triglyceride (TG)
      levels. Moreover, the TG-lowering capacities of compounds 6 and 10 were
      comparable with those of simvastatin, with the TG levels being nearly equal to
      blank control. This is the first report on the lipid-lowering activity of
      tanzawaic acid derivatives.

PMID- 29329206
TI  - Preparation of Cu2O-Reduced Graphene Nanocomposite Modified Electrodes towards
      Ultrasensitive Dopamine Detection.
AB  - Cu2O-reduced graphene oxide nanocomposite (Cu2O-RGO) was used to modify glassy
      carbon electrodes (GCE), and applied for the determination of dopamine (DA). The
      microstructure of Cu2O-RGO nanocomposite material was characterized by scanning
      electron microscope. Then the electrochemical reduction condition for preparing
      Cu2O-RGO/GCE and experimental conditions for determining DA were further
      optimized. The electrochemical behaviors of DA on the bare electrode, RGO- and
      Cu2O-RGO-modified electrodes were also investigated using cyclic voltammetry in
      phosphate-buffered saline solution (PBS, pH 3.5). The results show that the
      oxidation peaks of ascorbic acid (AA), dopamine (DA), and uric acid (UA) could be
      well separated and the peak-to-peak separations are 204 mV (AA-DA) and 144 mV (DA
      UA), respectively. Moreover, the linear response ranges for the determination of
      1 * 10-8 mol/L~1 * 10-6 mol/L and 1 * 10-6 mol/L~8 * 10-5 mol/L with the
      detection limit 6.0 * 10-9 mol/L (S/N = 3). The proposed Cu2O-RGO/GCE was further
      applied to the determination of DA in dopamine hydrochloride injections with
      satisfactory results.

PMID- 29329207
TI  - Arnica Tincture Cures Cutaneous Leishmaniasis in Golden Hamsters.
AB  - In search for potential therapeutic alternatives to existing treatments for
      cutaneous Leishmaniasis, we have investigated the effect of Arnica tincture Ph.
      Eur. (a 70% hydroethanolic tincture prepared from flowerheads of Arnica montana
      L.) on the lesions caused by infection with Leishmania braziliensis in a model
      with golden hamsters. The animals were treated topically with a daily single dose
      of the preparation for 28 days. Subsequently, the healing process was monitored
      by recording the lesion size in intervals of 15 days up to day 90. As a result,
      Arnica tincture fully cured three out of five hamsters while one animal showed an
      improvement and another one suffered from a relapse. This result was slightly
      better than that obtained with the positive control, meglumine antimonate, which
      cured two of five hamsters while the other three showed a relapse after 90 days.
      This result encourages us to further investigate the potential of Arnica tincture
      in the treatment of cutaneous Leishmaniasis.

PMID- 29329208
TI  - Advances in Molecular Profiling and Categorisation of Pancreatic Adenocarcinoma
      and the Implications for Therapy.
AB  - Pancreatic ductal adenocarcinoma (PDAC) continues to be a disease with poor
      outcomes and short-lived treatment responses. New information is emerging from
      genome sequencing identifying potential subgroups based on somatic and germline
      mutations. A variety of different mutations and mutational signatures have been
      identified; the driver mutation in around 93% of PDAC is KRAS, with other
      recorded alterations being SMAD4 and CDKN2A. Mutations in the deoxyribonucleic
      acid (DNA) damage repair pathway have also been investigated in PDAC and multiple
      clinical trials are ongoing with DNA-damaging agents. Rare mutations in BRAF and
      microsatellite instability (MSI) have been reported in about 1-3% of patients
      with PDAC, and agents used in other cancers to target these have also shown some
      promise. Immunotherapy is a developing field, but has failed to demonstrate
      benefits in PDAC to date. While many trials have failed to improve outcomes in
      this deadly disease, there is optimism that by developing a better understanding
      of the translational aspects of this cancer, future informed therapeutic
      strategies may prove more successful.

PMID- 29329210
TI  - An Over 90 dB Intra-Scene Single-Exposure Dynamic Range CMOS Image Sensor Using a
      3.0 MUm Triple-Gain Pixel Fabricated in a Standard BSI Process.
AB  - To respond to the high demand for high dynamic range imaging suitable for moving
      objects with few artifacts, we have developed a single-exposure dynamic range
      image sensor by introducing a triple-gain pixel and a low noise dual-gain readout
      circuit. The developed 3 MUm pixel is capable of having three conversion gains.
      Introducing a new split-pinned photodiode structure, linear full well reaches 40
      ke-. Readout noise under the highest pixel gain condition is 1 e- with a low
      noise readout circuit. Merging two signals, one with high pixel gain and high
      analog gain, and the other with low pixel gain and low analog gain, a single
      exposure dynamic rage (SEHDR) signal is obtained. Using this technology, a
      1/2.7", 2M-pixel CMOS image sensor has been developed and characterized. The
      image sensor also employs an on-chip linearization function, yielding a 16-bit
      linear signal at 60 fps, and an intra-scene dynamic range of higher than 90 dB
      was successfully demonstrated. This SEHDR approach inherently mitigates the
      artifacts from moving objects or time-varying light sources that can appear in
      the multiple exposure high dynamic range (MEHDR) approach.

PMID- 29329209
TI  - Gentamicin Sulfate PEG-PLGA/PLGA-H Nanoparticles: Screening Design and
      Antimicrobial Effect Evaluation toward Clinic Bacterial Isolates.
AB  - Nanotechnology is a promising approach both for restoring or enhancing activity
      of old and conventional antimicrobial agents and for treating intracellular
      infections by providing intracellular targeting and sustained release of drug
      inside infected cells. The present paper introduces a formulation study of
      gentamicin loaded biodegradable nanoparticles (Nps). Solid-oil-in water technique
      was studied for gentamicin sulfate nanoencapsulation using uncapped Polylactide
      co-glycolide (PLGA-H) and Polylactide-co-glycolide-co-Polyethylenglycol (PLGA
      PEG) blends. Screening design was applied to optimize: drug payload, Nps size and
      size distribution, stability and resuspendability after freeze-drying. PLGA-PEG
      concentration resulted most significant factor influencing particles size and
      drug content (DC): 8 w/w% DC and 200 nm Nps were obtained. Stirring rate resulted
      most influencing factor for size distribution (PDI): 700 rpm permitted to obtain
      homogeneous Nps dispersion (PDI = 1). Further experimental parameters
      investigated, by 23 screening design, were: polymer blend composition (PLGA-PEG
      and PLGA-H), Polyvinylalcohol (PVA) and methanol concentrations into aqueous
      phase. Drug content was increased to 10.5 w/w%. Nanoparticle lyophilization was
      studied adding cryoprotectants, polyvinypirrolidone K17 and K32, and
      sodiumcarboxymetylcellulose. Freeze-drying protocol was optimized by a mixture
      design. A freeze-dried Nps powder free resuspendable with stable Nps size and
      payload, was developed. The powder was tested on clinic bacterial isolates
      demonstrating that after encapsulation, gentamicin sulfate kept its activity.

PMID- 29329211
TI  - Causation of Acute Flaccid Paralysis by Myelitis and Myositis in Enterovirus-D68
      Infected Mice Deficient in Interferon alphabeta/gamma Receptor Deficient Mice.
AB  - Enterovirus D68 (EV-D68) caused a large outbreak in the summer and fall of 2014
      in the United States. It causes serious respiratory disease, but causation of
      associated paralysis is controversial, because the virus is not routinely
      identified in cerebrospinal fluid. To establish clinical correlates with human
      disease, we evaluated EV-D68 infection in non-lethal paralysis mouse models. Ten
      day-old mice lacking interferon responses were injected intraperitoneally with
      the virus. Paralysis developed in hindlimbs. After six weeks of paralysis, the
      motor neurons were depleted due to viral infection. Hindlimb muscles were also
      infected and degenerating. Even at the earliest stage of paralysis, muscles were
      still infected and were degenerating, in addition to presence of virus in the
      spinal cord. To model natural respiratory infection, five-day-old mice were
      infected intranasally with EV-D68. Two of the four infected mice developed
      forelimb paralysis. The affected limbs had muscle disease, but no spinal cord
      infection was detected. The unique contributions of this study are that EV-D68
      causes paralysis in mice, and that causation by muscle disease, with or without
      spinal cord disease, may help to resolve the controversy that the virus can cause
      paralysis, even if it cannot be identified in cerebrospinal fluid.

PMID- 29329212
TI  - Study of the Thermal Properties and the Fire Performance of Flame Retardant
      Organic PCM in Bulk Form.
AB  - The implementation of organic phase change materials (PCMs) in several
      applications such as heating and cooling or building comfort is an important
      target in thermal energy storage (TES). However, one of the major drawbacks of
      organic PCMs implementation is flammability. The addition of flame retardants to
      PCMs or shape-stabilized PCMs is one of the approaches to address this problem
      and improve their final deployment in the building material sector. In this
      study, the most common organic PCM, Paraffin RT-21, and fatty acids mixtures of
      capric acid (CA), myristic acid (MA), and palmitic acid (PA) in bulk, were tested
      to improve their fire reaction. Several flame retardants, such as ammonium
      phosphate, melamine phosphate, hydromagnesite, magnesium hydroxide, and aluminum
      hydroxide, were tested. The properties of the improved PCM with flame retardants
      were characterized by thermogravimetric analyses (TGA), the dripping test, and
      differential scanning calorimetry (DSC). The results for the dripping test show
      that fire retardancy was considerably enhanced by the addition of hydromagnesite
      (50 wt %) and magnesium hydroxide (50 wt %) in fatty acids mixtures. This will
      help the final implementation of these enhanced PCMs in building sector. The
      influence of the addition of flame retardants on the melting enthalpy and
      temperatures of PCMs has been evaluated.

PMID- 29329213
TI  - A Cross-Sectional Study of the Association between Infant Hepatitis B Vaccine
      Exposure in Boys and the Risk of Adverse Effects as Measured by Receipt of
      Special Education Services.
AB  - The National Center for Education Statistics reported that between 1990-2005 the
      number of children receiving special education services (SES) rose significantly,
      and then, from 2004-2012, the number declined significantly. This coincided with
      the introduction of Thimerosal-containing hepatitis B vaccine in 1991, and the
      subsequent introduction of Thimerosal-reduced hepatitis B vaccine in the early
      2000s. This study examined the potential relationship between infant exposure to
      mercury from three doses of Thimerosal-containing hepatitis B vaccine and the
      risk of boys being adversely affected (as measured by receipt of SES). This cross
      sectional study examined 1192 boys (weighted n = 24,537,123) 7-8 years of age
      (born: 1994-2007) from the combined 2001-2014 National Health and Nutritional
      Examination Survey (NHANES). Survey logistic regression modeling revealed that an
      exposed population receiving three doses of infant Thimerosal-containing
      hepatitis B vaccine (weighted n = 11,186,579), in comparison to an unexposed
      population (weighted n = 704,254), were at an increased risk of receipt of SES.
      This association was robust (crude odds ratio = 10.143, p = 0.0232), even when
      considering covariates, such as race and socioeconomic status (adjusted odds
      ratio = 9.234, p = 0.0259). Survey frequency modeling revealed that receipt of
      SES for the population that was exposed to three doses of Thimerosal-containing
      hepatitis B vaccine in infancy (12.91%) was significantly higher than the
      unexposed population (1.44%) (prevalence ratio = 8.96, p = 0.006, prevalence
      attributable rate = 0.1147). Despite the limitation of this cross-sectional study
      not being able to ascribe a direct cause-and-effect relationship between exposure
      and outcome, it is estimated that an additional 1.2 million boys received SES
      with excess education costs of about United States (US) $180 billion associated
      with exposure to Thimerosal-containing hepatitis B vaccine. By contrast, exposure
      to Thimerosal-reduced hepatitis B vaccine was not associated with an increased
      risk of receiving SES. Therefore, routine childhood vaccination is important to
      reduce the morbidity and mortality of infectious diseases, but every effort
      should be made to eliminate Thimerosal from all vaccines.

PMID- 29329214
TI  - Analysis of Emission Effects Related to Drivers' Compliance Rates for Cooperative
      Vehicle-Infrastructure System at Signalized Intersections.
AB  - Unknown remaining time of signal phase at a signalized intersection generally
      results in extra accelerations and decelerations that increase variations of
      operating conditions and thus emissions. A cooperative vehicle-infrastructure
      system can reduce unnecessary speed changes by establishing communications
      between vehicles and the signal infrastructure. However, the environmental
      benefits largely depend on drivers' compliance behaviors. To quantify the effects
      of drivers' compliance rates on emissions, this study applied VISSIM 5.20
      (Planung Transport Verkehr AG, Karlsruhe, Germany) to develop a simulation model
      for a signalized intersection, in which light duty vehicles were equipped with a
      cooperative vehicle-infrastructure system. A vehicle-specific power (VSP)-based
      model was used to estimate emissions. Based on simulation data, the effects of
      different compliance rates on VSP distributions, emission factors, and total
      emissions were analyzed. The results show the higher compliance rate decreases
      the proportion of VSP bin = 0, which means that the frequencies of braking and
      idling were lower and light duty vehicles ran more smoothly at the intersection
      if more light duty vehicles complied with the cooperative vehicle-infrastructure
      system, and emission factors for light duty vehicles decreased significantly as
      the compliance rate increased. The case study shows higher total emission
      reductions were observed with higher compliance rate for all of CO2, NOx, HC, and
      CO emissions. CO2 was reduced most significantly, decreased by 16% and 22% with
      compliance rates of 0.3 and 0.7, respectively.

PMID- 29329216
TI  - An Introduction to Integrative Genomics and Systems Medicine in Cancer.
AB  - In this Special Issue (SI), with a theme of "Integrative Genomics and Systems
      Medicine in Cancer", we have collected a total of 12 research and review articles
      from researchers in the field of genomics and systems medicine[...].

PMID- 29329217
TI  - Prey Acceptability and Preference of Oenopia conglobata (Coleoptera:
      Coccinellidae), a Candidate for Biological Control in Urban Green Areas.
AB  - Oenopia conglobata is one of the most common ladybird species in urban green
      areas of the Mediterranean region. We have obtained data about its prey
      acceptability and prey preferences. In a laboratory experiment, we investigated
      the acceptability of seven aphid and one psyllid species as prey for this
      coccinellid: the aphids Chaitophorus populeti, Aphis gossypii, Aphis
      craccivoraMonelliopsis caryae, Eucallipterus tiliae, Aphis nerii (on white
      poplar, pomegranate, false acacia, black walnut, lime, and oleander,
      respectively), and the psyllid Acizziajamatonica on Persian silk tree. These
      species are abundant in urban green areas in the Mediterranean region. In
      addition, we tested the acceptability of Rhopalosiphum padi on barley, an aphid
      species easily reared in the laboratory. We also tested preferences of the
      predator in cafeteria experiments with three aphid species and one aphid and the
      psyllid. Adults and larvae of the coccinellid accepted all of the preys offered,
      except A. nerii, with a clear preference for M. caryae. The predator also showed
      preference for M. caryae when it was offered in a cafeteria experiment with other
      aphid species or with the psyllid. The aphid R. padi obtained a good
      acceptability and could be used for rearing O. conglobata in the laboratory.

PMID- 29329215
TI  - Dietary Supplement of Large Yellow Tea Ameliorates Metabolic Syndrome and
      Attenuates Hepatic Steatosis in db/db Mice.
AB  - Yellow tea has been widely recognized for its health benefits. However, its
      effects and mechanism are largely unknown. The current study investigated the
      mechanism of dietary supplements of large yellow tea and its effects on metabolic
      syndrome and the hepatic steatosis in male db/db mice. Our data showed that
      dietary supplements of large yellow tea and water extract significantly reduced
      water intake and food consumption, lowered the serum total and low-density
      lipoprotein cholesterol and triglyceride levels, and significantly reduced blood
      glucose level and increased glucose tolerance in db/db mice when compared to
      untreated db/db mice. In addition, the dietary supplement of large yellow tea
      prevented the fatty liver formation and restored the normal hepatic structure of
      db/db mice. Furthermore, the dietary supplement of large yellow tea obviously
      reduced the lipid synthesis related to gene fatty acid synthase, the sterol
      regulatory element-binding transcription factor 1 and acetyl-CoA carboxylase
      alpha, as well as fatty acid synthase and sterol response element-binding protein
      1 expression, while the lipid catabolic genes were not altered in the liver of
      db/db mice. This study substantiated that the dietary supplement of large yellow
      tea has potential as a food additive for ameliorating type 2 diabetes-associated
      symptoms.

PMID- 29329218
TI  - Molecular and Physiological Effects on the Small Intestine of Weaner Pigs
      Following Feeding with Deoxynivalenol-Contaminated Feed.
AB  - We intended to assess how exposure of piglets to deoxynivalenol (DON)
      contaminated feed impacted their growth, immune response and gut development.
      Piglets were fed traditional Phase I, Phase II and Phase III diets with the
      control group receiving 0.20-0.40 ppm DON (referred to as the Control group) and
      treatment group receiving much higher level of DON-contaminated wheat (3.30-3.80
      ppm; referred to as DON-contaminated group). Feeding a DON-contaminated diet had
      no impact on average daily feed intake (ADFI) (p < 0.08) or average daily gain
      (ADG) (p > 0.10) but it did significantly reduce body weight over time relative
      to the control piglets (p < 0.05). Cytokine analysis after initial exposure to
      the DON-contaminated feed did not result in significant differences in serum
      interleukin (IL) IL1beta, IL-8, IL-13, tumor necrosis factor (TNF)-alpha or
      interferon (IFN)-gamma. After day 24, no obvious changes in jejunum or ileum gut
      morphology, histology or changes in gene expression for IL-1beta, IL-6, IL-10,
      TNFalpha, or Toll-like receptor (TLR)-4 genes. IL-8 showed a trend towards
      increased expression in the ileum in DON-fed piglets. A significant increase in
      gene expression for claudin (CLDN) 7 gene expression and a trend towards
      increased CLDN 2-expression was observed in the ileum in piglets fed the highly
      DON-contaminated wheat. Because CLDN localization was not negatively affected, we
      believe that it is unlikely that gut permeability was affected. Exposure to DON
      contaminated feed did not significantly impact weaner piglet performance or gut
      physiology.

PMID- 29329219
TI  - Modification of Boc-Protected CAN508 via Acylation and Suzuki-Miyaura Coupling.
AB  - The cyclin-dependent kinase inhibitor, CAN508, was protected with di-tert-butyl
      dicarbonate to access the amino-benzoylated pyrazoles. The bromo derivatives were
      further arylated by Suzuki-Miyaura coupling using the XPhos Pd G2 pre-catalyst.
      The coupling reaction provided generally the para-substituted benzoylpyrazoles in
      the higher yields than the meta-substituted ones. The Boc groups were only
      utilized as directing functionalities for the benzoylation step and were
      hydrolyzed under conditions of Suzuki-Miyaura coupling, which allowed for
      elimination of the additional deprotection step.

PMID- 29329220
TI  - Electrostatic Deposition of Large-Surface Graphene.
AB  - This work describes a method for electrostatic deposition of graphene over a
      large area using controlled electrostatic exfoliation from a Highly Ordered
      Pyrolytic Graphite (HOPG) block. Deposition over 130 * 130 um2 with 96% coverage
      is achieved, which contrasts with sporadic micro-scale depositions of graphene
      with little control from previous works on electrostatic deposition. The
      deposition results are studied by Raman micro-spectroscopy and hyperspectral
      analysis using large fields of view to allow for the characterization of the
      whole deposition area. Results confirm that laser pre-patterning of the HOPG
      block prior to cleaving generates anchor points favoring a more homogeneous and
      defect-free HOPG surface, yielding larger and more uniform graphene depositions.
      We also demonstrate that a second patterning of the HOPG block just before
      exfoliation can yield features with precisely controlled geometries.

PMID- 29329221
TI  - High-Temperature Sensor Based on Fabry-Perot Interferometer in Microfiber Tip.
AB  - A miniaturized tip Fabry-Perot interferometer (tip-FPI) is proposed for high
      temperature sensing. It is simply fabricated for the first time by splicing a
      short length of microfiber (MF) to the cleaved end of a standard single mode
      fiber (SMF) with precise control of the relative cross section position. Such a
      MF acts as a Fabry-Perot (FP) cavity and serves as a tip sensor. A change in
      temperature modifies the length and refractive index of the FP cavity, and then a
      corresponding change in the reflected interference spectrum can be observed. High
      temperatures of up to 1000  degrees C are measured in the experiments, and a high
      sensitivity of 13.6 pm/ degrees C is achieved. This compact sensor, with tip
      diameter and length both of tens of microns, is suitable for localized detection,
      especially in harsh environments.

PMID- 29329222
TI  - The Influence of EGFR Inactivation on the Radiation Response in High Grade
      Glioma.
AB  - Lack of effectiveness of radiation therapy may arise from different factors such
      as radiation induced receptor tyrosine kinase activation and cell repopulation;
      cell capability to repair radiation induced DNA damage; high grade glioma (HGG)
      tumous heterogeneity, etc. In this study, we analyzed the potential of targeting
      epidermal growth factor receptor (EGFR) in inducing radiosensitivity in two human
      HGG cell lines (11 and 15) that displayed similar growth patterns and expressed
      the receptor protein at the cell surface. We found that 15 HGG cells that express
      more EGFR at the cell surface were more sensitive to AG556 (an EGFR inhibitor),
      compared to 11 HGG cells. Although in line 15 the effect of the inhibitor was
      greater than in line 11, it should be noted that the efficacy of this small
      molecule EGFR inhibitor as monotherapy in both cell lines has been modest, at
      best. Our data showed a slight difference in the response to radiation of the HGG
      cell lines, three days after the treatment, with line 15 responding better than
      line 11. However, both cell lines responded to ionizing radiation in the same
      way, seven days after irradiation. EGFR inhibition induced radiosensitivity in 11
      HGG cells, while, in 15 HGG cells, the effect of AG556 treatment on radiation
      response was almost nonexistent.

PMID- 29329224
TI  - Melanin-Based Functional Materials.
AB  - Melanin biopolymers are currently the focus of growing interest for a broad range
      of applications at the cutting edge of biomedical research and technology. This
      Special Issue presents a collection of papers dealing with melanin-type
      materials, e.g., polydopamine, for classic and innovative applications, offering
      a stimulating perspective of current trends in the field. Besides basic
      scientists, the Special Issue is directed to researchers from industries and
      companies that are willing to invest in melanin research for innovative and
      inspiring solutions.

PMID- 29329225
TI  - Optical Fiber Demodulation System with High Performance for Assessing Fretting
      Damage of Steam Generator Tubes.
AB  - In order to access the fretting damage of the steam generator tube (SGT), a fast
      fiber Fabry-Perot (F-P) non-scanning correlation demodulation system based on a
      super luminescent light emitting diode (SLED) was performed. By demodulating the
      light signal coming out from the F-P force sensor, the radial collision force
      between the SGT and the tube support plate (TSP) was interrogated. For higher
      demodulation accuracy, the effects of the center wavelength, bandwidth, and
      spectrum noise of SLED were discussed in detail. Specially, a piezoelectric
      ceramic transducer (PZT) modulation method was developed to get rid of the
      interference of mode coupling induced by different types of fiber optics in the
      demodulation system. The reflectivity of optical wedge and F-P sensor was
      optimized. Finally, the demodulation system worked well in a 1:1 steam generator
      test loop and successfully demodulated a force signal of 32 N with a collision
      time of 2 ms.

PMID- 29329226
TI  - Plils: A Practical Indoor Localization System through Less Expensive Wireless
      Chips via Subregion Clustering.
AB  - Reducing costs is a pragmatic method for promoting the widespread usage of indoor
      localization technology. Conventional indoor localization systems (ILSs) exploit
      relatively expensive wireless chips to measure received signal strength for
      positioning. Our work is based on a cheap and widely-used commercial off-the
      shelf (COTS) wireless chip, i.e., the Nordic Semiconductor nRF24LE1, which has
      only several output power levels, and proposes a new power level based-ILS,
      called Plils. The localization procedure incorporates two phases: an offline
      training phase and an online localization phase. In the offline training phase, a
      self-organizing map (SOM) is utilized for dividing a target area into k
      subregions, wherein their grids in the same subregion have similar fingerprints.
      In the online localization phase, the support vector machine (SVM) and back
      propagation (BP) neural network methods are adopted to identify which subregion a
      tagged object is located in, and calculate its exact location, respectively. The
      reasonable value for k has been discussed as well. Our experiments show that
      Plils achieves 75 cm accuracy on average, and is robust to indoor obstacles.

PMID- 29329223
TI  - Mast Cells: Key Contributors to Cardiac Fibrosis.
AB  - Historically, increased numbers of mast cells have been associated with fibrosis
      in numerous cardiac pathologies, implicating mast cells in the development of
      cardiac fibrosis. Subsequently, several approaches have been utilised to
      demonstrate a causal role for mast cells in animal models of cardiac fibrosis
      including mast cell stabilising compounds, rodents deficient in mast cells, and
      inhibition of the actions of mast cell-specific proteases such as chymase and
      tryptase. Whilst most evidence supports a pro-fibrotic role for mast cells, there
      is evidence that in some settings these cells can oppose fibrosis. A major gap in
      our current understanding of cardiac mast cell function is identification of the
      stimuli that activate these cells causing them to promote a pro-fibrotic
      environment. This review will present the evidence linking mast cells to cardiac
      fibrosis, as well as discuss the major questions that remain in understanding how
      mast cells contribute to cardiac fibrosis.

PMID- 29329227
TI  - Fermentation-Guided Natural Products Isolation of a Grape Berry Triacylglyceride
      that Enhances Ethyl Ester Production.
AB  - A full understanding of the origin, formation and degradation of volatile
      compounds that contribute to wine aroma is required before wine style can be
      effectively managed. Fractionation of grapes represents a convenient and robust
      method to simplify the grape matrix to enhance our understanding of the grape
      contribution to volatile compound production during yeast fermentation. In this
      study, acetone extracts of both Riesling and Cabernet Sauvignon grape berries
      were fractionated and model wines produced by spiking aliquots of these grape
      fractions into model grape juice must and fermented. Non-targeted SPME-GCMS
      analyses of the wines showed that several medium chain fatty acid ethyl esters
      were more abundant in wines made by fermenting model musts spiked with certain
      fractions. Further fractionation of the non-polar fractions and fermentation of
      model must after addition of these fractions led to the identification of a
      mixture of polyunsaturated triacylglycerides that, when added to fermenting model
      must, increase the concentration of medium chain fatty acid ethyl esters in
      wines. Dosage-response fermentation studies with commercially-available
      trilinolein revealed that the concentration of medium chain fatty acid ethyl
      esters can be increased by the addition of this triacylglyceride to model musts.
      This work suggests that grape triacylglycerides can enhance the production of
      fermentation-derived ethyl esters and show that this fractionation method is
      effective in segregating precursors or factors involved in altering the
      concentration of fermentation volatiles.

PMID- 29329229
TI  - Chemical Composition and Evaluation of the Biological Properties of the Essential
      Oil of the Dietary Phytochemical Lippia citriodora.
AB  - The aim of the study was to characterize the chemical composition and biological
      properties of the essential oil from the plant Lippia citriodora grown in Greece.
      The essential oil volatiles were analyzed by gas chromatography-mass spectrometry
      GC-MS indicating citral as the major component. Tauhe antimicrobial properties
      were assayed using the disk diffusion method and the minimum inhibitory and non
      inhibitory concentration values were determined. Listeria monocytogenes,
      Staphylococcus epidermidis, Staphylococcus aureus, Saccharomyces cerevisiae, and
      Aspergillus niger were sensitive to Lippia citriodora oil, but not Escherichia
      coli, Salmonella Enteritidis, Salmonella typhimurium, and Pseudomonas fragi.
      Adversely, all microbes tested were sensitive to citral. 2,2-Diphenyl-1
      picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid)
      (ABTS) assays were used to assess direct antioxidant activity, which proved to be
      weak for both agents, while comet assay was utilized to study the cytoprotective
      effects against H2O2-induced oxidative damage in Jurkat cells. Interestingly, the
      oil showed a more profound cytoprotective effect compared to citral. The
      antiproliferative activity was evaluated in a panel of cancer cell lines using
      the sulforhodamine B (SRB) and 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-S
      (phenylamino) carbonyl-2-tetrazolium hydroxide (XTT) assays and both agents
      demonstrated potent antiproliferative activity with citral being more cytotoxic
      than the oil. Taken together, the essential oil of Lippia citriodora and its
      major component, citral, exert diverse biological properties worthy of further
      investigation.

PMID- 29329228
TI  - Current NMR Techniques for Structure-Based Drug Discovery.
AB  - A variety of nuclear magnetic resonance (NMR) applications have been developed
      for structure-based drug discovery (SBDD). NMR provides many advantages over
      other methods, such as the ability to directly observe chemical compounds and
      target biomolecules, and to be used for ligand-based and protein-based
      approaches. NMR can also provide important information about the interactions in
      a protein-ligand complex, such as structure, dynamics, and affinity, even when
      the interaction is too weak to be detected by ELISA or fluorescence resonance
      energy transfer (FRET)-based high-throughput screening (HTS) or to be
      crystalized. In this study, we reviewed current NMR techniques. We focused on
      recent progress in NMR measurement and sample preparation techniques that have
      expanded the potential of NMR-based SBDD, such as fluorine NMR (19F-NMR)
      screening, structure modeling of weak complexes, and site-specific isotope
      labeling of challenging targets.

PMID- 29329230
TI  - Metagenomic Virome Analysis of Culex Mosquitoes from Kenya and China.
AB  - Many blood-feeding arthropods are known vectors of viruses that are a source of
      unprecedented global health concern. Mosquitoes are an integral part of these
      arthropod vectors. Advancements in next-generation sequencing and bioinformatics
      has expanded our knowledge on the richness of viruses harbored by arthropods. In
      the present study, we applied a metagenomic approach to determine the
      intercontinental virome diversity of Culex quinquefasciatus and Culex
      tritaeniorhynchus in Kwale, Kenya and provinces of Hubei and Yunnan in China. Our
      results showed that viromes from the three locations were strikingly diverse and
      comprised 30 virus families specific to vertebrates, invertebrates, plants, and
      protozoa as well as unclassified group of viruses. Though sampled at different
      times, both Kwale and Hubei mosquito viromes were dominated by vertebrate
      viruses, in contrast to the Yunnan mosquito virome, which was dominated by insect
      specific viruses. However, each virome was unique in terms of virus proportions
      partly influenced by type of ingested meals (blood, nectar, plant sap,
      environment substrates). The dominant vertebrate virus family in the Kwale virome
      was Papillomaviridae (57%) while in Hubei it was Herpesviridae (30%) and the
      Yunnan virome was dominated by an unclassified viruses group (27%). Given that
      insect-specific viruses occur naturally in their hosts, they should be the basis
      for defining the viromes. Hence, the dominant insect-specific viruses in Kwale,
      Hubei, and Yunnan were Baculoviridae, Nimaviridae and Iflaviridae, respectively.
      Our study is preliminary but contributes to growing and much needed knowledge, as
      mosquito viromes could be manipulated to prevent and control pathogenic
      arboviruses.

PMID- 29329231
TI  - Development of a Cytocompatible Scaffold from Pig Immature Testicular Tissue
      Allowing Human Sertoli Cell Attachment, Proliferation and Functionality.
AB  - Cryopreservation of immature testicular tissue before chemo/radiotherapy is the
      only option to preserve fertility of cancer-affected prepubertal boys. To avoid
      reintroduction of malignant cells, development of a transplantable scaffold by
      decellularization of pig immature testicular tissue (ITT) able to support
      decontaminated testicular cells could be an option for fertility restoration in
      these patients. We, therefore, compared decellularization protocols to produce a
      cytocompatible scaffold. Fragments of ITT from 15 piglets were decellularized
      using three protocols: sodium dodecyl sulfate (SDS)-Triton (ST), Triton-SDS
      Triton (TST) and trypsin 0.05%/ethylenediaminetetraacetic acid (EDTA) 0.02%
      Triton (TET) with varying detergent concentrations. All protocols were able to
      lower DNA levels. Collagen retention was demonstrated in all groups except ST 1%,
      and a significant decrease in glycosaminoglycans was observed in the TST 1% and
      TET 1% groups. When Sertoli cells (SCs) were cultured with decellularized tissue,
      no signs of cytotoxicity were detected. A higher SC proliferation rate and
      greater stem cell factor secretion were observed than with SCs cultured without
      scaffold. ST 0.01% and TET 3% conditions offered the best compromise in terms of
      DNA elimination and extracellular matrix (ECM) preservation, while ensuring good
      attachment, proliferation and functionality of human SCs. This study demonstrates
      the potential of using decellularized pig ITT for human testicular tissue
      engineering purposes.

PMID- 29329232
TI  - Novel 6- and 7-Substituted Coumarins with Inhibitory Action against Lipoxygenase
      and Tumor-Associated Carbonic Anhydrase IX.
AB  - A series of carboxamide derivatives of 6- and 7-substituted coumarins have been
      prepared by an original procedure starting from the corresponding 6- or 7
      hydroxycoumarins which were alkylated with ethyl iodoacetate, and the obtained
      ester was converted to the corresponding carboxylic acids which were thereafter
      reacted with a series of aromatic/aliphatic/heterocyclic amines leading to the
      desired amides. The new derivatives were investigated as inhibitors of two
      enzymes, human carbonic anhydrases (hCAs) and soy bean lipoxygenase (LOX).
      Compounds 4a and 4b were potent LOX inhibitors, whereas many effective hCA IX
      inhibitors (KIs in the range of 30.2-30.5 nM) were detected in this study. Two
      compounds, 4b and 5b, showed the phenomenon of dual inhibition. Furthermore,
      these coumarins did not significantly inhibit the widespread cytosolic isoforms
      hCA I and II, whereas they were weak hCA IV inhibitors, making them hCA IX
      selective inhibitors. As hCA IX and LOX are validated antitumor targets, these
      results are promising for the investigation of novel drug targets involved in
      tumorigenesis.

PMID- 29329234
TI  - Poor People Are Hospitalized Three Times More for Mental Health Services than the
      Non-Poor in Central Valley California.
AB  - Introduction: Providing health insurance to the poor has become a standard policy
      response to health disparities between the poor and the non-poor. It is often
      assumed that if the poor people are given health insurance, they will use
      preventative care, which will prevent more expensive emergency visits and
      inpatient hospitalization, and in turn, it will save healthcare cost in the long
      run. This paper presents the findings from our study in California about what
      happens to the poor when they are given health insurance. The purpose of the
      study was to understand how the healthcare system in California treats the poor
      patients differently than the non-poor. Method: Using multivariate logistic
      regressions, this study analyzed a large patient discharge data (PDD) from the
      California Office of Statewide Planning and Development (OSHPD) for eight
      counties in the Central Valley California (N = 423,640). First, utilizing
      International Classification of Diseases (ICD 10) as diagnostic criteria, mental
      health vs. non-mental health hospitalization rates were estimated. Second, health
      insurance status was used as a proxy measure of poverty of the patients. Using
      chi-Square, the probability of hospitalization for mental health services was
      estimated based on their insurance types. Finally, using step-wise logistic
      regression, the odds of mental health hospitalization was estimated conditional
      on individual characteristics, health insurance types, and geographic
      characteristics. Findings: When the poor people were given health insurance, they
      were three times more likely to be hospitalized for mental health services than
      the non-poor. The more than three-fold variation in mental health hospitalization
      was not driven by demographic or geographic characteristics. The findings are new
      and have important implications for the healthcare policies for the poor. Further
      studies are needed to understand the extent to which the disproportionately high
      rate of mental health hospitalizations of the poor are driven by the provider
      induced needs.

PMID- 29329233
TI  - Dose-Dependent Effects of Randomized Intraduodenal Whey-Protein Loads on Glucose,
      Gut Hormone, and Amino Acid Concentrations in Healthy Older and Younger Men.
AB  - Protein-rich supplements are used widely for the prevention and management of
      malnutrition in older people. We have reported that healthy older, compared to
      younger, adults have less suppression of energy intake by whey-protein-effects on
      appetite-related hormones are unknown. The objective was to determine the effects
      of intraduodenally administered whey-protein on glucose, gut hormone, and amino
      acid concentrations, and their relation to subsequent ad libitum energy intake at
      a buffet meal, in healthy older and younger men. Hydrolyzed whey-protein (30
      kcal, 90 kcal, and 180 kcal) and a saline control (~0 kcal) were infused
      intraduodenally for 60 min in 10 younger (19-29 years, 73 +/- 2 kg, 22 +/- 1
      kg/m2) and 10 older (68-81 years, 79 +/- 2 kg, 26 +/- 1 kg/m2) healthy men in a
      randomized, double-blind fashion. Plasma insulin, glucagon, gastric inhibitory
      peptide (GIP), glucagon-like peptide-1 (GLP-1), peptide tyrosine-tyrosine (PYY),
      and amino acid concentrations, but not blood glucose, increased, while ghrelin
      decreased during the whey-protein infusions. Plasma GIP concentrations were
      greater in older than younger men. Energy intake correlated positively with
      plasma ghrelin and negatively with insulin, glucagon, GIP, GLP-1, PYY, and amino
      acids concentrations (p < 0.05). In conclusion, intraduodenal whey-protein
      infusions resulted in increased GIP and comparable ghrelin, insulin, glucagon,
      GIP, GLP-1, PYY, and amino acid responses in healthy older and younger men, which
      correlated to subsequent energy intake.

PMID- 29329236
TI  - Gender-Associated Impact of Early Leucine Supplementation on Adult Predisposition
      to Obesity in Rats.
AB  - Early nutrition plays an important role in development and may constitute a
      relevant contributor to the onset of obesity in adulthood. The aim of this study
      was to evaluate the long-term impact of maternal leucine (Leu) supplementation
      during lactation on progeny in rats. A chow diet, supplemented with 2% Leu, was
      supplied during lactation (21 days) and, from weaning onwards, was replaced by a
      standard chow diet. Then, at adulthood (6 months of age), this was replaced with
      hypercaloric diets (either with high-fat (HF) or high-carbohydrate (HC) content),
      for two months, to induce obesity. Female offspring from Leu-supplemented dams
      showed higher increases in body weight and in body fat (62%) than their
      respective controls; whereas males were somehow protected (15% less fat than the
      corresponding controls). This profile in Leu-females was associated with altered
      neuronal architecture at the paraventricular nucleus (PVN), involving
      neuropeptide Y (NPY) fibers and impaired expression of neuropeptides and factors
      of the mTOR signaling pathway in the hypothalamus. Interestingly, leptin and
      adiponectin expression in adipose tissue at weaning and at the time before the
      onset of obesity could be defined as early biomarkers of metabolic disturbance,
      predisposing towards adult obesity under the appropriate environment.

PMID- 29329235
TI  - A Review of the Biological Activities of Microalgal Carotenoids and Their
      Potential Use in Healthcare and Cosmetic Industries.
AB  - Carotenoids are natural pigments that play pivotal roles in many physiological
      functions. The characteristics of carotenoids, their effects on health, and the
      cosmetic benefits of their usage have been under investigation for a long time;
      however, most reviews on this subject focus on carotenoids obtained from several
      microalgae, vegetables, fruits, and higher plants. Recently, microalgae have
      received much attention due to their abilities in producing novel bioactive
      metabolites, including a wide range of different carotenoids that can provide for
      health and cosmetic benefits. The main objectives of this review are to provide
      an updated view of recent work on the health and cosmetic benefits associated
      with carotenoid use, as well as to provide a list of microalgae that produce
      different types of carotenoids. This review could provide new insights to
      researchers on the potential role of carotenoids in improving human health.

PMID- 29329237
TI  - mTOR Pathways in Cancer and Autophagy.
AB  - TOR (target of rapamycin), an evolutionarily-conserved serine/threonine kinase,
      acts as a central regulator of cell growth, proliferation and survival in
      response to nutritional status, growth factor, and stress signals. It plays a
      crucial role in coordinating the balance between cell growth and cell death,
      depending on cellular conditions and needs. As such, TOR has been identified as a
      key modulator of autophagy for more than a decade, and several deregulations of
      this pathway have been implicated in a variety of pathological disorders,
      including cancer. At the molecular level, autophagy regulates several survival or
      death signaling pathways that may decide the fate of cancer cells; however, the
      relationship between autophagy pathways and cancer are still nascent. In this
      review, we discuss the recent cellular signaling pathways regulated by TOR, their
      interconnections to autophagy, and the clinical implications of TOR inhibitors in
      cancer.

PMID- 29329239
TI  - Fine Regulation of Neutrophil Oxidative Status and Apoptosis by Ceruloplasmin and
      Its Derivatives.
AB  - Timely neutrophil apoptosis is an essential part of the resolution phase of acute
      inflammation. Ceruloplasmin, an acute-phase protein, which is the predominant
      copper-carrying protein in the blood, has been suggested to have a marked effect
      on neutrophil life span. The present work is a comparative study on the effects
      of intact holo-ceruloplasmin, its copper-free (apo-) and partially proteolyzed
      forms, and synthetic free peptides RPYLKVFNPR (883-892) and RRPYLKVFNPRR (882
      893) on polymorphonuclear leukocyte (PMNL, neutrophil) oxidant status and
      apoptosis. The most pronounced effect on both investigated parameters was found
      with copper-containing samples, namely, intact and proteolyzed proteins. Both
      effectively reduced spontaneous and tumor necrosis factor-alpha (TNF-alpha)
      induced extracellular and intracellular accumulation of superoxide radicals, but
      induced a sharp increase in the oxidation of intracellular 2',7'
      dichlorofluorescein upon short exposure. Therefore, intact and proteolyzed
      ceruloplasmin have both anti- and pro-oxidant effects on PMNLs wherein the latter
      effect is diminished by TNF-alpha and lactoferrin. Additionally, all compounds
      investigated were determined to be inhibitors of delayed spontaneous apoptosis.
      Intact enzyme retained its pro-survival activity, whereas proteolytic degradation
      converts ceruloplasmin from a mild inhibitor to a potent activator of TNF-alpha
      induced neutrophil apoptosis.

PMID- 29329240
TI  - Effective Data-Driven Calibration for a Galvanometric Laser Scanning System Using
      Binocular Stereo Vision.
AB  - A new solution to the problem of galvanometric laser scanning (GLS) system
      calibration is presented. Under the machine learning framework, we build a single
      hidden layer feedforward neural network (SLFN)to represent the GLS system, which
      takes the digital control signal at the drives of the GLS system as input and the
      space vector of the corresponding outgoing laser beam as output. The training
      data set is obtained with the aid of a moving mechanism and a binocular stereo
      system. The parameters of the SLFN are efficiently solved in a closed form by
      using extreme learning machine (ELM). By quantitatively analyzing the regression
      precision with respective to the number of hidden neurons in the SLFN, we
      demonstrate that the proper number of hidden neurons can be safely chosen from a
      broad interval to guarantee good generalization performance. Compared to the
      traditional model-driven calibration, the proposed calibration method does not
      need a complex modeling process and is more accurate and stable. As the output of
      the network is the space vectors of the outgoing laser beams, it costs much less
      training time and can provide a uniform solution to both laser projection and 3D
      reconstruction, in contrast with the existing data-driven calibration method
      which only works for the laser triangulation problem. Calibration experiment,
      projection experiment and 3D reconstruction experiment are respectively conducted
      to test the proposed method, and good results are obtained.

PMID- 29329241
TI  - Sino-Austrian High-Tech Acupuncture Network: Annual Report 2017.
AB  - The Sino-Austrian High-Tech Acupuncture Research Network was founded in 2005 and
      has been growing ever since. The network comprises many partners from China and
      is highly involved in research and education activities. This report introduces
      the network's activities in the year 2017.

PMID- 29329238
TI  - Long-Chain Metabolites of Vitamin E: Metabolic Activation as a General Concept
      for Lipid-Soluble Vitamins?
AB  - Vitamins E, A, D and K comprise the class of lipid-soluble vitamins. For vitamins
      A and D, a metabolic conversion of precursors to active metabolites has already
      been described. During the metabolism of vitamin E, the long-chain metabolites
      (LCMs) 13'-hydroxychromanol (13'-OH) and 13'-carboxychromanol (13'-COOH) are
      formed by oxidative modification of the side-chain. The occurrence of these
      metabolites in human serum indicates a physiological relevance. Indeed, effects
      of the LCMs on lipid metabolism, apoptosis, proliferation and inflammatory
      actions as well as tocopherol and xenobiotic metabolism have been shown.
      Interestingly, there are several parallels between the actions of the LCMs of
      vitamin E and the active metabolites of vitamin A and D. The recent findings that
      the LCMs exert effects different from that of their precursors support their
      putative role as regulatory metabolites. Hence, it could be proposed that the
      mode of action of the LCMs might be mediated by a mechanism similar to vitamin A
      and D metabolites. If the physiological relevance and this concept of action of
      the LCMs can be confirmed, a general concept of activation of lipid-soluble
      vitamins via their metabolites might be deduced.

PMID- 29329242
TI  - Absorption and Metabolism of Phenolics from Digests of Polyphenol-Rich Potato
      Extracts Using the Caco-2/HepG2 Co-Culture System.
AB  - The bioactivity of dietary polyphenols depends upon gastrointestinal and hepatic
      metabolism of secondary microbial phenolic metabolites generated via colonic
      microbiota-mediated biotransformation. A polyphenol-rich potato extract (PRPE)
      containing chlorogenic, caffeic, and ferulic acids and rutin was digested in a
      dynamic multi-reactor gastrointestinal simulator of the human intestinal
      microbial ecosystem (GI model). Simulated digestion showed extensive degradation
      of the parent compounds and the generation of microbial phenolic metabolites. To
      characterize the transport and metabolism of microbial phenolic metabolites
      following digestion, a co-culture of intestinal Caco-2 and hepatic HepG2 cells
      was exposed to the PRPE-derived digests obtained from the colonic vessels.
      Following a 2 h incubation of the digesta with the Caco-2/HepG2 co-cultures,
      approximately 10-15% of ferulic, dihydrocaffeic, and dihydroferulic acids and 3
      5% of 3-hydroxybenzoic, 3-hydroxyphenylpropionic, and coumaric acids were
      observed in the basolateral side, whereas 3-hydroxyphenylacetic acid,
      phenylpropanoic acid, and cinnamic acid were not detected. Subsequent HepG2
      cellular metabolism led to major increases in ferulic, dihydrocaffeic, 3
      hydroxyphenylpropionic, and coumaric acids ranging from 160-370%. These findings
      highlight the importance of hepatic metabolism towards the generation of
      secondary metabolites of polyphenols despite low selective Caco-2 cellular uptake
      of microbial phenolic metabolites.

PMID- 29329243
TI  - Characteristics of BeiDou Navigation Satellite System Multipath and Its
      Mitigation Method Based on Kalman Filter and Rauch-Tung-Striebel Smoother.
AB  - Global Navigation Satellite System (GNSS) carrier phase measurement for short
      baseline meets the requirements of deformation monitoring of large structures.
      However, the carrier phase multipath effect is the main error source with double
      difference (DD) processing. There are lots of methods to deal with the multipath
      errors of Global Position System (GPS) carrier phase data. The BeiDou navigation
      satellite System (BDS) multipath mitigation is still a research hotspot because
      the unique constellation design of BDS makes it different to mitigate multipath
      effects compared to GPS. Multipath error periodically repeats for its strong
      correlation to geometry of satellites, reflective surface and antenna which is
      also repetitive. We analyzed the characteristics of orbital periods of BDS
      satellites which are consistent with multipath repeat periods of corresponding
      satellites. The results show that the orbital periods and multipath periods for
      BDS geostationary earth orbit (GEO) and inclined geosynchronous orbit (IGSO)
      satellites are about one day but the periods of MEO satellites are about seven
      days. The Kalman filter (KF) and Rauch-Tung-Striebel Smoother (RTSS) was
      introduced to extract the multipath models from single difference (SD) residuals
      with traditional sidereal filter (SF). Wavelet filter and Empirical mode
      decomposition (EMD) were also used to mitigate multipath effects. The
      experimental results show that the three filters methods all have obvious effect
      on improvement of baseline accuracy and the performance of KT-RTSS method is
      slightly better than that of wavelet filter and EMD filter. The baseline vector
      accuracy on east, north and up (E, N, U) components with KF-RTSS method were
      improved by 62.8%, 63.6%, 62.5% on day of year 280 and 57.3%, 53.4%, 55.9% on day
      of year 281, respectively.

PMID- 29329245
TI  - Underwater Object Segmentation Based on Optical Features.
AB  - Underwater optical environments are seriously affected by various optical inputs,
      such as artificial light, sky light, and ambient scattered light. The latter two
      can block underwater object segmentation tasks, since they inhibit the emergence
      of objects of interest and distort image information, while artificial light can
      contribute to segmentation. Artificial light often focuses on the object of
      interest, and, therefore, we can initially identify the region of target objects
      if the collimation of artificial light is recognized. Based on this concept, we
      propose an optical feature extraction, calculation, and decision method to
      identify the collimated region of artificial light as a candidate object region.
      Then, the second phase employs a level set method to segment the objects of
      interest within the candidate region. This two-phase structure largely removes
      background noise and highlights the outline of underwater objects. We test the
      performance of the method with diverse underwater datasets, demonstrating that it
      outperforms previous methods.

PMID- 29329244
TI  - Infant Development at the Age of 6 Months in Relation to Feeding Practices, Iron
      Status, and Growth in a Peri-Urban Community of South Africa.
AB  - BACKGROUND: Evidence on the association between feeding practices, iron
      deficiency, anaemia, stunting, and impaired psychomotor development during
      infancy is limited. This study assessed the association between psychomotor
      development with early feeding practices, growth, iron status, and anaemia.
      METHODS: This was cross-sectional baseline data of a randomised controlled trial
      which included 6-month-old infants and their mothers or primary caregivers (n =
      750) in a peri-urban community in the North West province of South Africa. The
      Kilifi Developmental Inventory and a parent rating scale were used to assess
      psychomotor development. Feeding practices and anthropometric measurements were
      based on the World Health Organisation (WHO) guidelines. Anaemia and iron status
      were determined by blood sample analysis. RESULTS: Prevalence of anaemia and
      stunting for the infants were 36.4% and 28.5%, respectively. Multiple regression
      analysis showed that birth weight was related to combined psychomotor scores
      (beta = -3.427 (-4.603, 1.891), p < 0.001), as well as parent rating scores (beta
      = -0.843 (-1.507, -0.180), p = 0.013). Length-for-age z-scores were associated
      with combined psychomotor scores (beta = -1.419 (-2.466, 0.373), p = 0.008), as
      well as parent rating scores (beta = -0.747 (-1.483, -0.010), p = 0.047).
      CONCLUSIONS: In this setting, with high prevalence of anaemia and stunting,
      important associations between lower psychomotor development scores and
      birthweight as well as length-for-age z-scores in 6-month-old infants were found.
      These findings warrant further investigation to develop a greater understanding
      of factors influencing the association between child growth and psychomotor
      development within the first 1000 days of life.

PMID- 29329246
TI  - Socioeconomic Inequalities in the Use of Healthcare Services: Comparison between
      the Roma and General Populations in Spain.
AB  - This paper explores whether the principles of horizontal and vertical equity in
      healthcare are met by the Spanish national health system in the case of the Roma
      and general populations. The 2011/2012 Spanish National Health Survey (n =
      21,650) and the 2014 National Health Survey of the Spanish Roma Population (n =
      1167) were analyzed. Use of healthcare services was measured in terms of visits
      to a general practitioner (GP), visits to an emergency department, and
      hospitalizations. Healthcare need was measured using (a) self-rated health and
      (b) the reported number of chronic diseases. The Roma reported worse self-rated
      health and a higher prevalence of chronic diseases. A redistributive effect
      (increased healthcare service use among Roma and those in lower socio-economic
      classes) was found for hospitalizations and emergency visits. This effect was
      also observed in GP visits for women, but not for men. Vertical inequity was
      observed in the general population but not in the Roma population for GP visits.
      The results suggest the existence of horizontal inequity in the use of GP
      services (Roma women), emergency department visits (Roma and general population),
      and hospitalizations (Roma population) and of vertical inequity in the use of GP
      services among the general population.

PMID- 29329248
TI  - Performance Analysis of Millimeter-Wave Multi-hop Machine-to-Machine Networks
      Based on Hop Distance Statistics.
AB  - As an intrinsic part of the Internet of Things (IoT) ecosystem, machine-to
      machine (M2M) communications are expected to provide ubiquitous connectivity
      between machines. Millimeter-wave (mmWave) communication is another promising
      technology for the future communication systems to alleviate the pressure of
      scarce spectrum resources. For this reason, in this paper, we consider multi-hop
      M2M communications, where a machine-type communication (MTC) device with the
      limited transmit power relays to help other devices using mmWave. To be specific,
      we focus on hop distance statistics and their impacts on system performances in
      multi-hop wireless networks (MWNs) with directional antenna arrays in mmWave for
      M2M communications. Different from microwave systems, in mmWave communications,
      wireless channel suffers from blockage by obstacles that heavily attenuate line
      of-sight signals, which may result in limited per-hop progress in MWNs. We
      consider two routing strategies aiming at different types of applications and
      derive the probability distributions of their hop distances. Moreover, we provide
      their baseline statistics assuming the blockage-free scenario to quantify the
      impact of blockages. Based on the hop distance analysis, we propose a method to
      estimate the end-to-end performances (e.g., outage probability, hop count, and
      transmit energy) of the mmWave MWNs, which provides important insights into
      mmWave MWN design without time-consuming and repetitive end-to-end simulation.

PMID- 29329247
TI  - A Simple Method to Measure Renal Function in Swine by the Plasma Clearance of
      Iohexol.
AB  - There is no simple method to measure glomerular filtration rate (GFR) in swine,
      an established model for studying renal disease. We developed a protocol to
      measure GFR in conscious swine by using the plasma clearance of iohexol. We used
      two groups, test and validation, with eight animals each. Ten milliliters of
      iohexol (6.47 g) was injected into the marginal auricular vein and blood samples
      (3 mL) were collected from the orbital sinus at different points after injection.
      GFR was determined using two models: two-compartment (CL2: all samples) and one
      compartment (CL1: the last six samples). In the test group, CL1 overestimated CL2
      by ~30%: CL2 = 245 +/- 93 and CL1 = 308 +/- 123 mL/min. This error was corrected
      by a first-order polynomial quadratic equation to CL1, which was considered the
      simplified method: SM = -47.909 + (1.176xCL1) - (0.00063968xCL12). The SM showed
      narrow limits of agreement with CL2, a concordance correlation of 0.97, and a
      total deviation index of 14.73%. Similar results were obtained for the validation
      group. This protocol is reliable, reproducible, can be performed in conscious
      animals, uses a single dose of the marker, and requires a reduced number of
      samples, and avoids urine collection. Finally, it presents a significant
      improvement in animal welfare conditions and handling necessities in experimental
      trials.

PMID- 29329250
TI  - Blood Flow and Continuous EEG Changes during Symptomatic Plateau Waves.
AB  - Benign meningiomas uncommonly lead to significant cerebral edema, with only a few
      cases previously reported in the medical literature. The present study describes
      the case of a 49-year-old female who had a meningioma resection. She subsequently
      developed malignant cerebral edema and had episodes that were initially
      concerning for seizure activity. However, transient blood flow changes concerning
      for intracranial pressure (ICP) crises, were demonstrated on electroencephalogram
      (EEG) as well as noninvasive cerebral blood flow monitoring. The present case
      highlights the importance of close monitoring in patients with post meningioma
      resection cerebral edema because of the possibility of ICP crises.

PMID- 29329249
TI  - Scaffolding for Repair: Understanding Molecular Functions of the SMC5/6 Complex.
AB  - Chromosome organization, dynamics and stability are required for successful
      passage through cellular generations and transmission of genetic information to
      offspring. The key components involved are Structural maintenance of chromosomes
      (SMC) complexes. Cohesin complex ensures proper chromatid alignment, condensin
      complex chromosome condensation and the SMC5/6 complex is specialized in the
      maintenance of genome stability. Here we summarize recent knowledge on the
      composition and molecular functions of SMC5/6 complex. SMC5/6 complex was
      originally identified based on the sensitivity of its mutants to genotoxic stress
      but there is increasing number of studies demonstrating its roles in the control
      of DNA replication, sister chromatid resolution and genomic location-dependent
      promotion or suppression of homologous recombination. Some of these functions
      appear to be due to a very dynamic interaction with cohesin or other repair
      complexes. Studies in Arabidopsis indicate that, besides its canonical function
      in repair of damaged DNA, the SMC5/6 complex plays important roles in regulating
      plant development, abiotic stress responses, suppression of autoimmune responses
      and sexual reproduction.

PMID- 29329251
TI  - Pharmacological Investigation of the Anti-Inflammation and Anti-Oxidation
      Activities of Diallyl Disulfide in a Rat Emphysema Model Induced by Cigarette
      Smoke Extract.
AB  - Diallyl disulfide (DADS) is the main organosulfur ingredient in garlic, with
      known antioxidant and anti-inflammatory activities. The aim of the present study
      was to investigate the effect of DADS on reducing the inflammation and redox
      imbalance in a rat emphysema model that was induced by intraperitoneal injection
      of cigarette smoke extract (CSE). Briefly, DADS exerted an anti-inflammation
      effect on emphysema rats through decreasing cell influx in the bronchoalveolar
      lavage fluid (BALF) and suppressing pro-inflammation cytokine production
      including tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta),
      interleukin-6 (IL-6) via inhibiting the NF-kappaB pathway. In addition, levels of
      oxidative stress markers including malondialdehyde (MDA) and myeloperoxidase
      (MPO) were reduced, while the activities of glutathione (GSH), glutathione
      peroxidase (GSH-PX), superoxide dismutase (SOD) and total antioxidant capacity (T
      AOC) were markedly enhanced by DADS. Moreover, MMP-9 and TIMP-1 expression were
      down-regulated by DADS. Furthermore, the regulation effects of DADS on CD4+ and
      CD8+ T cells were observed. In conclusion, these encouraging findings suggest
      that DADS could be considered as a promising anti-inflammation and antioxidative
      agent for the treatment of emphysema.

PMID- 29329255
TI  - Peri-Implant Behavior of Sloped Shoulder Dental Implants Used for All-On-Four
      Protocols: An Histomorphometric Analysis in Dogs.
AB  - The aim of this study was to evaluate the soft tissue thickness and marginal bone
      loss around dental implants with sloped micro-threaded shoulder (35 degrees 
      angle) in comparing with conventional design, inserted 35 degrees  degrees
      angulated in post extraction sockets and immediate loaded with temporary
      prosthesis simulating the all-on-four protocol. Materials and Methods: Six fox
      hound dogs received forty-eight post extraction dental implants with the same
      diameter and length (Medentika, Germany), but with different neck configurations.
      Two group of implants were inserted 1mm subcrestal. Control group has a micro
      threaded neck and the Test group has a sloped microthreaded neck. Immediate
      loading was applied using a constructed metallic structure. After three months,
      soft and hard tissue levels were assessed by histomorphometric analysis. Results:
      The mean soft tissue thickness (STT) was 2.5 +/- 0.2 mm for the Control group and
      3.3 +/- 0.3 mm for Test group (p = 0.036), meanwhile the mean marginal bone loss
      (MBL) was 1.53 +/- 0.34 mm for Control group and, 1.62 +/- 0.22 mm for Test group
      (p > 0.05). Conclusions: Within the limitations of this experimental model in
      dogs, the findings showed that dental implants with microthreaded and
      microthreaded sloped necks installed in immediate post extraction sites with
      immediate load, presented a comparable perimplant tissue behavior.

PMID- 29329254
TI  - Low-Carbohydrate, High-Protein, High-Fat Diets Rich in Livestock, Poultry and
      Their Products Predict Impending Risk of Type 2 Diabetes in Chinese Individuals
      that Exceed Their Calculated Caloric Requirement.
AB  - The evidence on the association between long-term low-carbohydrate, high-fat and
      high-protein diets and type 2 diabetes (T2D) is controversial. Until now, data is
      limited for Chinese populations, especially in considering the influence of extra
      energy intake. In this paper, we aimed to investigate the association of low
      carbohydrate, high-fat and high-protein diets with type 2 diabetes (T2D) risk in
      populations consuming extra calories and those with normal caloric intake, We
      also determined whether the association is mediated by insulin resistance (IR) or
      beta-cell dysfunction. A total of 3644 subjects in the Harbin People's Health
      Study (Cohort 1, 2008-2012) and 7111 subjects in the Harbin Cohort Study on Diet,
      Nutrition and Chronic Non-Communicable Diseases (Cohort 2, 2010-2015) were
      analyzed, with a median follow-up of 4.2 and 5.3 years, respectively.
      Multivariate relative risks (RRs) and their 95% confidence intervals (95% CIs)
      were calculated to estimate the association between low-carbohydrate, high-fat
      and high-protein diet and T2D in logistic regression models. The multivariate RRs
      (95% CIs) were 1.00, 2.24 (1.07, 4.72) and 2.29 (1.07, 4.88) (Ptrend = 0.04), and
      1.00, 1.45 (0.91, 2.31) and 1.64 (1.03, 2.61) (Ptrend = 0.04) across tertiles of
      low-carbohydrate, high-fat and high-protein diet scores in the population
      consuming extra calories in Cohort 1 and Cohort 2, respectively. The association
      was no longer significant after adjustment for livestock and its products, or
      poultry and its products. The mediation analysis discovered that this association
      in the population consuming extra calories was insulin resistance mediated, in
      both Cohort 1 and Cohort 2. However, the association was not significant among
      participants overall and participants with normal caloric intake. Our results
      indicated that long-term low-carbohydrate, high-fat and high-protein diets were
      associated with increased T2D risk among the population consuming extra calories,
      which may be caused by higher intake of animal-origin fat and protein as well as
      lower intake of vegetables, fruit and fiber. Additionally, the association was
      mediated by IR. In the population consuming extra calories, reducing the intake
      of livestock, poultry and their products and increasing the intake of vegetables,
      fruit and fiber might protect this population from developing T2D.

PMID- 29329256
TI  - Personalized Antidepressant Selection and Pathway to Novel Treatments: Clinical
      Utility of Targeting Inflammation.
AB  - Major depressive disorder (MDD) is a chronic condition that affects one in six
      adults in the US during their lifetime. The current practice of antidepressant
      medication prescription is a trial-and-error process. Additionally, over a third
      of patients with MDD fail to respond to two or more antidepressant treatments.
      There are no valid clinical markers to personalize currently available
      antidepressant medications, all of which have similar mechanisms targeting
      monoamine neurotransmission. The goal of this review is to summarize the recent
      findings of immune dysfunction in patients with MDD, the utility of inflammatory
      markers to personalize treatment selection, and the potential of targeting
      inflammation to develop novel antidepressant treatments. To personalize
      antidepressant prescription, a c-reactive protein (CRP)-matched treatment
      assignment can be rapidly implemented in clinical practice with point-of-care
      fingerstick tests. With this approach, 4.5 patients need to be treated for 1
      additional remission as compared to a CRP-mismatched treatment assignment. Anti
      cytokine treatments may be effective as novel antidepressants. Monoclonal
      antibodies against proinflammatory cytokines, such as interleukin 6, interleukin
      17, and tumor necrosis factor alpha, have demonstrated antidepressant effects in
      patients with chronic inflammatory conditions who report significant depressive
      symptoms. Additional novel antidepressant strategies targeting inflammation
      include pharmaceutical agents that block the effect of systemic inflammation on
      the central nervous system. In conclusion, inflammatory markers offer the
      potential not only to personalize antidepressant prescription but also to guide
      the development of novel mechanistically-guided antidepressant treatments.

PMID- 29329259
TI  - Extreme Overvalued Beliefs: How Violent Extremist Beliefs Become "Normalized".
AB  - Extreme overvalued beliefs (EOB) are rigidly held, non-deusional beliefs that are
      the motive behind most acts of terrorism and mass shootings. EOBs are
      differentiated from delusions and obsessions. The concept of an overvalued idea
      was first described by Wernicke and later applied to terrorism by McHugh. Our
      group of forensic psychiatrists (Rahman, Resnick, Harry) refined the definition
      as an aid in the differential diagnosis seen in acts of violence. The form and
      content of EOBs is discussed as well as group effects, conformity, and obedience
      to authority. Religious cults such as The People's Temple, Heaven's Gate, Aum
      Shinrikyo, and Islamic State (ISIS) and conspiracy beliefs such as
      assassinations, moon-hoax, and vaccine-induced autism beliefs are discussed using
      this construct. Finally, some concluding thoughts on countering violent
      extremism, including its online presence is discussed utilizing information
      learned from online eating disorders and consumer experience.

PMID- 29329258
TI  - Association between Haem and Non-Haem Iron Intake and Serum Ferritin in Healthy
      Young Women.
AB  - Iron is an essential micronutrient for human health and inadequate intake may
      result in iron deficiency (ID) or iron deficiency anaemia (IDA). Unlike other
      recent studies investigating iron status in young women, this cross-sectional
      study analysed dietary intake and biochemical data from healthy young (18-35
      years) women (n = 299) to determine the association between both haem iron (HI)
      and non-haem iron (NHI) intakes and serum ferritin (SF). Dietary restraint and
      possible inflammation secondary to obesity were also measured and accounted for,
      and energy intake was adjusted for using the residuals method. Independent
      samples t-tests and chi-squared tests were performed, and factors found to be
      significantly different between iron replete (IR) and ID/IDA participants were
      analysed using general linear modelling. ID/IDA participants consumed
      significantly lower total energy than iron replete (IR) (p = 0.003). Lower energy
      intake was also associated with higher levels of dietary restraint (p = 0.001).
      Both HI and NHI were positively associated with SF with HI was found to be a
      stronger predictor (beta = 0.128, p = 0.009) than NHI (beta = 0.037, p = 0.028).
      The study demonstrates that intake of both HI and NHI, as well as adequate
      dietary energy, are associated with normal iron status levels in young women, and
      that restrained eaters may be at greater risk of low iron status.

PMID- 29329260
TI  - Effects of Zr Addition on Strengthening Mechanisms of Al-Alloyed High-Cr ODS
      Steels.
AB  - Oxide dispersion strengthened (ODS) steels with different contents of zirconium
      (denoted as 16Cr ODS, 16Cr-0.3Zr ODS and 16Cr-0.6Zr ODS) were fabricated to
      investigate the effects of Zr on strengthening mechanism of Al-alloyed 16Cr ODS
      steel. Electron backscatter diffraction (EBSD) results show that the mean grain
      size of ODS steels could be decreased by Zr addition. Transmission electron
      microscope (TEM) results indicate that Zr addition could increase the number
      density but decrease the mean diameter and inter-particle spacing of oxide
      particles. Furthermore, it is also found that in addition to Y-Al-O
      nanoparticles, Y-Zr-O oxides with finer size were observed in 16Cr-0.3Zr ODS and
      16Cr-0.6Zr ODS steels. These changes in microstructure significantly increase the
      yield strength (YS) and ultimate tensile strength (UTS) of ODS steels through
      mechanisms of grain boundary strengthening and dispersion strengthening.

PMID- 29329261
TI  - Sitting Posture Monitoring System Based on a Low-Cost Load Cell Using Machine
      Learning.
AB  - Sitting posture monitoring systems (SPMSs) help assess the posture of a seated
      person in real-time and improve sitting posture. To date, SPMS studies reported
      have required many sensors mounted on the backrest plate and seat plate of a
      chair. The present study, therefore, developed a system that measures a total of
      six sitting postures including the posture that applied a load to the backrest
      plate, with four load cells mounted only on the seat plate. Various machine
      learning algorithms were applied to the body weight ratio measured by the
      developed SPMS to identify the method that most accurately classified the actual
      sitting posture of the seated person. After classifying the sitting postures
      using several classifiers, average and maximum classification rates of 97.20% and
      97.94%, respectively, were obtained from nine subjects with a support vector
      machine using the radial basis function kernel; the results obtained by this
      classifier showed a statistically significant difference from the results of
      multiple classifications using other classifiers. The proposed SPMS was able to
      classify six sitting postures including the posture with loading on the backrest
      and showed the possibility of classifying the sitting posture even though the
      number of sensors is reduced.

PMID- 29329257
TI  - Synthesis and Pharmacological Activities of Pyrazole Derivatives: A Review.
AB  - Pyrazole and its derivatives are considered a pharmacologically important active
      scaffold that possesses almost all types of pharmacological activities. The
      presence of this nucleus in pharmacological agents of diverse therapeutic
      categories such as celecoxib, a potent anti-inflammatory, the antipsychotic
      CDPPB, the anti-obesity drug rimonabant, difenamizole, an analgesic, betazole, a
      H2-receptor agonist and the antidepressant agent fezolamide have proved the
      pharmacological potential of the pyrazole moiety. Owing to this diversity in the
      biological field, this nucleus has attracted the attention of many researchers to
      study its skeleton chemically and biologically. This review highlights the
      different synthesis methods and the pharmacological properties of pyrazole
      derivatives. Studies on the synthesis and biological activity of pyrazole
      derivatives developed by many scientists around the globe are reported.

PMID- 29329262
TI  - Contamination and Risk Assessment of Estrogens in Livestock Manure: A Case Study
      in Jiangsu Province, China.
AB  - This study investigated the occurrence and contamination risk of estrogens in
      livestock manure in Jiangsu Province, China. Four estrogens-estriol (E3), 17beta
      estradiol (17beta-E2), bisphenol A (BPA), and 17alpha-ethinyloestradiol (EE2)
      were detected in livestock manure from hens, ducks, swine, and cows. The
      respective mean concentrations of each estrogen found in these manures were
      289.8, 334.1, 330.3, and 33.7 MUg/kg for E3; 38.6, 10.9, 52.9, and 38.8 MUg/kg
      for 17beta-E2; 63.6, 48.7, 51.9, and 11.7 MUg/kg for BPA; and 14.3, 11.3, 25.1,
      and 21.8 MUg/kg for EE2. Estrogens were most frequently detected at high
      concentrations in the manure of finishing pigs, followed by the manure of growing
      pigs and piglets. Estrogens can be partially degraded after banking up for seven
      days; yet, great quantities of estrogens remain in livestock manure. The total
      estradiol equivalent quantity (EEQt) estimated to be present in aquatic
      environments but originating from livestock waste was 10.5 ng/L, which was
      greater than the hazard baseline value (1 ng/L) and also higher than the proposed
      lowest observable effect concentration (10 ng/L) of E2 in aquatic environments.
      The results of our study demonstrate that livestock waste is an important source
      of estrogens, which may potentially affect the hormonal metabolism of aquatic
      organisms.

PMID- 29329263
TI  - Effect of Radiological Countermeasures on Subjective Well-Being and Radiation
      Anxiety after the 2011 Disaster: The Fukushima Health Management Survey.
AB  - After the Fukushima Daiichi Nuclear Power Station accident in 2011, concerns
      about radiation exposure and decline in subjective well-being have been reported.
      To tackle these problems, various countermeasures in relation to radiation have
      been implemented. In this study, we comprehensively evaluated the effects of
      radiological countermeasures on subjective well-being (e.g., satisfaction with
      life (SWL) and emotional well-being) and radiation anxiety, through a
      questionnaire survey targeting Fukushima residents (N = 1023). Propensity scores
      matching was applied to evaluate significant effects of radiological
      countermeasures on subjective well-being and radiation anxiety. Among the
      radiological countermeasures, thyroid examination, whole body counter, and air
      dose monitoring showed the highest proportions of participation, utilization, and
      useful evaluation, suggesting a high degree of public attention focused on these
      countermeasures. The basic survey was associated with significant increases in
      SWL and self-rated health (SH). Thyroid examination was significantly associated
      with not only a reduction in radiation anxiety but also an increase of emotional
      stress, suggesting the importance of careful design of system and detailed
      communication. Food inspection was associated with deterioration in SH. Those who
      utilized explanatory meetings showed increases in sadness, worry, and radiation
      anxiety, indicating that additional attention is required of the experts and
      authorities involved in explanatory meetings.

PMID- 29329264
TI  - Engineering Ru@Pt Core-Shell Catalysts for Enhanced Electrochemical Oxygen
      Reduction Mass Activity and Stability.
AB  - Improving the performance of oxygen reduction reaction (ORR) electrocatalysts is
      essential for the commercial efficacy of many renewable energy technologies,
      including low temperature polymer electrolyte fuel cells (PEFCs). Herein, we
      report highly active and stable carbon-supported Ru@Pt core-shell nanoparticles
      (Ru@Pt/C) prepared by a wet chemical synthesis technique. Through rotating disc
      electrode testing, the Ru@Pt/C achieves an ORR Pt mass-based activity of 0.50 A
      mgPt-1 at 0.9 V versus the reversible hydrogen electrode (RHE), which exceeds the
      activity of the state-of-the-art commercial Pt/C catalyst as well as the
      Department of Energy 2020 PEFC electrocatalyst activity targets for
      transportation applications. The impact of various synthetic parameters,
      including Pt to Ru ratios and catalyst pretreatments (i.e., annealing) are
      thoroughly explored. Pt-based mass activity of all prepared Ru@Pt/C catalysts was
      found to exceed 0.4 mgPt-1 across the range of compositions investigated, with
      the maximum activity catalyst having a Ru:Pt ratio of 1:1. This optimized
      composition of Ru@Pt/C catalyst demonstrated remarkable stability after 30,000
      accelerated durability cycles (0.6 to 1.0 V vs. RHE at 125 mV s-1), maintaining
      85% of its initial mass activity. Scanning transmission electron microscopy
      energy dispersive spectroscopy (STEM-EDS) analysis at various stages of
      electrochemical testing demonstrated that the Pt shell can provide sufficient
      protection against the dissolution of the otherwise unstable Ru core.

PMID- 29329265
TI  - Multiple-Octave-Spanning Vibration Sensing Based on Simultaneous Vector
      Demodulation of 499 Fizeau Interference Signals from Identical Ultra-Weak Fiber
      Bragg Gratings Over 2.5 km.
AB  - Multi-point vibration sensing at the low frequency range of 0.5-100 Hz is of
      vital importance for applications such as seismic monitoring and underwater
      acoustic imaging. Location-resolved multi-point sensing using a single fiber and
      a single demodulation system can greatly reduce system deployment and maintenance
      costs. We propose and demonstrate the demodulation of a fiber-optic system
      consisting of 500 identical ultra-weak Fiber Bragg gratings (uwFBGs), capable of
      measuring the amplitude, frequency and phase of acoustic signals from 499 sensing
      fibers covering a total range of 2.5 km. For demonstration purposes, we
      arbitrarily chose six consecutive sensors and studied their performance in
      detail. Using a passive demodulation method, we interrogated the six sensors
      simultaneously, and achieved a high signal-to-noise ratio of 22.1 dB, excellent
      linearity, phase sensitivity of around 0.024 rad/Pa, and a dynamic range of about
      38 dB. We demonstrated a frequency response flatness of <1.2 dB in the range of
      0.5-100 Hz. Compared to the prior state-of-the-art demonstration using a similar
      method, we have increased the sensing range from 1 km to 2.5 km, and increased
      the frequency range from 0.4 octaves to 7.6 octaves, in addition to achieving
      sensing in the very challenging low-frequency range of 0.5-100 Hz.

PMID- 29329266
TI  - Relative Validity of a 24-h Recall in Assessing Intake of Key Nutrients in a
      Cohort of Australian Toddlers.
AB  - There is limited information concerning the dietary intake of toddlers in
      Australia. Consequently, there is a need for studies investigating toddler intake
      that use dietary assessment measures that are valid and place a low participant
      burden on caregivers. The aim of this study was to determine the relative
      validity of a single 24-h dietary recall (24HR) in measuring the intake of five
      nutrients in a cohort of Australian toddlers compared to a combined 24HR and 2
      day estimated food record (2DFR). A single 24HR and a 2DFR were collected from a
      cohort of Australian toddlers (n = 699) at approximately 12 months of age as part
      of the Study of Mothers' and Infants' Life Events affecting oral health (SMILE)
      project. Relative validity of one day of dietary data (24HR) in assessing intake
      of energy, protein, calcium, iron, and added sugars was tested against three days
      of dietary data (24HR + 2DFR) using paired t-tests, Bland-Altman analysis, cross
      classification, and weighted Kappa statistic. Classification analysis found good
      agreement between the 24HR and 24HR + 2DFR for all nutrients with the percentage
      classified in the same tertile at 57.9% and above. The weighted Kappa statistic
      found acceptable agreement for all nutrients. This study suggests that a 24HR is
      a valid assessment tool for estimating the relative intake of energy, protein,
      calcium, iron, and added sugars among Australian toddlers at the individual
      level.

PMID- 29329267
TI  - A Mild Aqueous Sonogashira Reaction as a Fluorescent Labeling Strategy for 5
      Bromide-2'-Deoxyuridine.
AB  - C5-modified uridines are a valuable class of nucleoside analogues, both as potent
      chemotherapy agents and through their use as the conjunction site in DNA labeling
      strategies. As an important C5-modified uridine, BrdU has been used in cell
      proliferation assays since the 1980s. Currently, the detection of BrdU relies on
      traditional immunostaining; however, this approach has its limitations. Thus, it
      is desirable, albeit difficult, to develop chemistry methods to fluorescently
      label BrdU in a cellular context. In the present study, we report our efforts
      toward developing a robust chemistry methodology for BrdU fluorescent labeling.
      The Sonogashira reaction was chosen as the key reaction, and various alkynyl
      groups (aliphatic or aryl) containing fluorescent dyes were synthesized to cross
      couple with BrdU. Various bases and catalyst systems were screened to evaluate
      the optimum conditions. A mild aqueous Sonogashira reaction (K2PdCl4, S-Phos, n
      Bu4N+OH-, Sodium d-isoascorbate, EtOH/H2O = 1:1, 37  degrees C, Ar) was obtained
      to enable high-yielding BrdU fluorescent labeling.

PMID- 29329268
TI  - Anomaly Detection in Nanofibrous Materials by CNN-Based Self-Similarity.
AB  - Automatic detection and localization of anomalies in nanofibrous materials help
      to reduce the cost of the production process and the time of the post-production
      visual inspection process. Amongst all the monitoring methods, those exploiting
      Scanning Electron Microscope (SEM) imaging are the most effective. In this paper,
      we propose a region-based method for the detection and localization of anomalies
      in SEM images, based on Convolutional Neural Networks (CNNs) and self-similarity.
      The method evaluates the degree of abnormality of each subregion of an image
      under consideration by computing a CNN-based visual similarity with respect to a
      dictionary of anomaly-free subregions belonging to a training set. The proposed
      method outperforms the state of the art.

PMID- 29329269
TI  - Design, Synthesis, and Safener Activity of Novel Methyl (R)-N
      Benzoyl/Dichloroacetyl-Thiazolidine-4-Carboxylates.
AB  - A series of novel methyl (R)-N-benzoyl/dichloroacetyl-thiazolidine-4-carboxylates
      were designed by active substructure combination. The title compounds were
      synthesized using a one-pot route from l-cysteine methyl ester hydrochloride,
      acyl chloride, and ketones. All compounds were characterized by IR, 1H NMR, 13C
      NMR, and HRMS. The structure of 4q was determined by X-ray crystallography. The
      biological tests showed that the title compounds protected maize from chlorimuron
      ethyl injury to some extent. The ALS activity assay showed that the title
      compounds increased the ALS activity of maize inhibited by chlorimuron-ethyl.
      Molecular docking modeling demonstrated that Compound 4e competed against
      chlorimuron-ethyl to combine with the herbicide target enzyme active site,
      causing the herbicide to be ineffective.

PMID- 29329270
TI  - Toxicity Evaluation of Individual and Mixtures of Nanoparticles Based on Algal
      Chlorophyll Content and Cell Count.
AB  - The toxic effects of individual and binary mixtures of five metal oxide
      nanoparticles (NPs) were evaluated based on changes in two endpoints of algal
      growth: the cell count and chlorophyll content. Various effects were observed
      according to the concentration tested and type of NPs, and there were no
      significant differences in findings for the two endpoints. In general, ZnO NPs
      caused the greatest inhibition of algal growth, and Fe2O3 NPs the least. The EC50
      for ZnO was 2.0 mg/L for the cell count and 2.6 mg/L for the chlorophyll content,
      and it was 76 and 90 mg/L, respectively, for Fe2O3. The EC50 values were in the
      order ZnO > NiO > CuO > TiO2 > Fe2O3. Subsequently, the effects of 30 binary
      mixture combinations on the chlorophyll content were evaluated. Comparisons were
      made between the observed and the expected toxicities calculated based on the
      individual NP toxicities. Overall, additive action (67%) was mainly observed,
      followed by antagonistic (16.5%) and synergistic (16.5%) actions. These results
      suggest that environmental exposure to NP mixtures may cause toxicity levels
      similar to the sum of those of the constituent NPs.

PMID- 29329271
TI  - Transketolase Is Identified as a Target of Herbicidal Substance alpha-Terthienyl
      by Proteomics.
AB  - alpha-terthienyl is a natural phytotoxin isolated originally from Flaveria
      bidentis (L.) Kuntze. The bioassay presented here shows the strong herbicidal
      activity of alpha-terthienyl on Digitaria sanguinalis, Arabidopsis thaliana and
      Chlamydomonas reinhardtii. The alpha-terthienyl-induced response of A. thaliana
      at the protein level was analyzed at different times. Changes in the protein
      expression profiles were analyzed by two-dimensional gel electrophoresis and
      liquid chromatography tandem mass spectrometry (LC-MS/MS) mass spectrometry.
      Sixteen protein spots were identified that showed reproducible changes in the
      expression of at least 2-fold when compared to the control. Among these 16 spots,
      three were up-regulated and 13 were down-regulated. The decreased expression of
      several proteins associated with energy production and carbon metabolism
      suggested that these processes were affected by alpha-terthienyl. To search for
      the candidate proteins in this screen, A. thaliana T-DNA mutants of the candidate
      proteins were used to test their susceptibility to alpha-terthienyl. Amongst the
      others, attkl1, a mutant of transketolase, exhibited a significantly lower
      sensitivity to alpha-terthienyl when hit compared with Col-0. Based on the
      identification of the proteins associated with the response to alpha-terthienyl
      by proteomics, a candidate target protein transketolase was identified.

PMID- 29329272
TI  - Rapid Screening and Identification of Daidzein Metabolites in Rats Based on UHPLC
      LTQ-Orbitrap Mass Spectrometry Coupled with Data-Mining Technologies.
AB  - Daidzein, the main bioactive soy isoflavone in Nature, has been found to possess
      many biological functions. It has been investigated in particular as a
      phytoestrogen owing to the similarity of its structure with that of the human
      hormone estrogen. Due to the lack of comprehensive studies on daidzein
      metabolism, further research is still required to clarify its in vivo metabolic
      fate and intermediate processes. In this study, an efficient strategy was
      established using UHPLC-LTQ-Orbitrap mass spectrometry to profile the metabolism
      of daidzein in rats. Meanwhile, multiple data-mining methods including high
      resolution extracted ion chromatogram (HREIC), multiple mass defect filtering
      (MMDF), neutral loss fragment (NLF), and diagnostic product ion (DPI) were
      utilized to investigate daidzein metabolites from the HR-ESI-MS1 to ESI-MSn stage
      in both positive and negative ion modes. Consequently, 59 metabolites, including
      prototype compounds, were positively or tentatively elucidated based on reference
      standards, accurate mass measurements, mass fragmentation behaviors,
      chromatographic retention times, and corresponding calculated ClogP values. As a
      result, dehydration, hydrogenation, methylation, dimethylation, glucuronidation,
      glucosylation, sulfonation, ring-cleavage, and their composite reactions were
      ascertained to interpret its in vivo biotransformation. Overall, our results not
      only revealed the potential pharmacodynamics forms of daidzein, but also aid in
      establishing a practical strategy for rapid screening and identifying metabolites
      of natural compounds.

PMID- 29329273
TI  - Transcriptomics Evidence for Common Pathways in Human Major Depressive Disorder
      and Glioblastoma.
AB  - Depression as a common complication of brain tumors. Is there a possible common
      pathogenesis for depression and glioma? The most serious major depressive
      disorder (MDD) and glioblastoma (GBM) in both diseases are studied, to explore
      the common pathogenesis between the two diseases. In this article, we first rely
      on transcriptome data to obtain reliable and useful differentially expressed
      genes (DEGs) by differential expression analysis. Then, we used the
      transcriptomics of DEGs to find out and analyze the common pathway of MDD and GBM
      from three directions. Finally, we determine the important biological pathways
      that are common to MDD and GBM by statistical knowledge. Our findings provide the
      first direct transcriptomic evidence that common pathway in two diseases for the
      common pathogenesis of the human MDD and GBM. Our results provide a new reference
      methods and values for the study of the pathogenesis of depression and
      glioblastoma.

PMID- 29329275
TI  - Chitosan-Starch Films with Natural Extracts: Physical, Chemical, Morphological
      and Thermal Properties.
AB  - The aim of this study is to analyze the properties of a series of polysaccharide
      composite films, such as apparent density, color, the presence of functional
      groups, morphology, and thermal stability, as well as the correlation between
      them and their antimicrobial and optical properties. Natural antioxidants such as
      anthocyanins (from cranberry; blueberry and pomegranate); betalains (from
      beetroot and pitaya); resveratrol (from grape); and thymol and carvacrol (from
      oregano) were added to the films. Few changes in the position and intensity of
      the FTIR spectra bands were observed despite the low content of extract added to
      the films. Due to this fact, the antioxidants were extracted and identified by
      spectroscopic analysis; and they were also quantified using the Folin-Denis
      method and a gallic acid calibration curve, which confirmed the presence of
      natural antioxidants in the films. According to the SEM analysis, the presence of
      natural antioxidants has no influence on the film morphology because the stretch
      marks and white points that were observed were related to starch presence. On the
      other hand, the TGA analysis showed that the type of extract influences the total
      weight loss. The overall interpretation of the results suggests that the use of
      natural antioxidants as additives for chitosan-starch film preparation has a
      prominent impact on most of the critical properties that are decisive in making
      them suitable for food-packing applications.

PMID- 29329274
TI  - Current Technologies of Electrochemical Immunosensors: Perspective on Signal
      Amplification.
AB  - An electrochemical immunosensor employs antibodies as capture and detection means
      to produce electrical charges for the quantitative analysis of target molecules.
      This sensor type can be utilized as a miniaturized device for the detection of
      point-of-care testing (POCT). Achieving high-performance analysis regarding
      sensitivity has been one of the key issues with developing this type of biosensor
      system. Many modern nanotechnology efforts allowed for the development of
      innovative electrochemical biosensors with high sensitivity by employing various
      nanomaterials that facilitate the electron transfer and carrying capacity of
      signal tracers in combination with surface modification and bioconjugation
      techniques. In this review, we introduce novel nanomaterials (e.g., carbon
      nanotube, graphene, indium tin oxide, nanowire and metallic nanoparticles) in
      order to construct a high-performance electrode. Also, we describe how to
      increase the number of signal tracers by employing nanomaterials as carriers and
      making the polymeric enzyme complex associated with redox cycling for signal
      amplification. The pros and cons of each method are considered throughout this
      review. We expect that these reviewed strategies for signal enhancement will be
      applied to the next versions of lateral-flow paper chromatography and
      microfluidic immunosensor, which are considered the most practical POCT biosensor
      platforms.

PMID- 29329277
TI  - Synthesis, Structural Characterization, Antimicrobial Activity, and In Vitro
      Biocompatibility of New Unsaturated Carboxylate Complexes with 2,2'-Bipyridine.
AB  - The synthesis, structural characterization, cytotoxicity, and antimicrobial
      properties of four new complexes formed by employing acrylate anion and 2,2'
      bipyridine are reported herein. X-ray crystallography revealed the trinuclear
      nature of [Mn3(2,2'-bipy)2(C3H3O2)6] (1), meanwhile complexes with general
      formula [M(2,2'-bipy)(C3H3O2)2(H2O)x]?yH2O ((2) M: Ni, x = 1, y = 0; (3) M: Cu, x
      = 1, y = 0; (4) M: Zn, x = 0, y = 1; 2,2'-bipy: 2,2'-bipyridine; C3H3O2: acrylate
      anion) were shown to be mononuclear. The lowest minimum inhibitory concentration
      (MIC) of 128 MUg mL-1 was recorded for all four tested complexes against Candida
      albicans, for complex (3) against Escherichia coli, and for complex (4) against
      Staphylocococcus aureus. Compounds (3) and (4) were also potent efflux pumps
      activity inhibitors (EPI), proving their potential for use in synergistic
      combinations with antibiotics. Complexes (1)-(4) revealed that they were not
      cytotoxic to HCT-8 cells. They also proved to interfere with the cellular cycle
      of tumour HCT-8 cells by increasing the number of cells found in the S and G2/M
      phases. Taken together, these results demonstrate the potential of zinc and
      copper complexes for use in the development of novel antimicrobial and anti
      proliferative agents.

PMID- 29329276
TI  - The Safety of the Neighborhood Environment and Physical Activity in Czech and
      Polish Adolescents.
AB  - (1) Background: An increase in or at least the sustainment of walking activities
      across a wide section of the population is a crucial health-related task for
      Central and East European countries. The aim of this study was to assess the
      associations between adolescents' walking activities and various levels of
      perceived safety of the built environment in differing socio-demographic
      backgrounds of Poland and the Czech Republic. Furthermore, we aimed to determine
      major moderators affecting the walking habits of adolescents in areas with
      different levels of walkability. (2) Methods: The surveys were conducted during
      the 2008-2009 and 2013-2014 school years in 24 Polish and 35 Czech secondary
      schools, with a sample of 2001 adolescents. All participants completed the
      International Physical Activity Questionnaire-Long Form and the NEWS-Abbreviated.
      Selected students took part in objective weekly monitoring of physical activity
      (PA). (3) Results: Boys and girls who perceived their neighborhood environment as
      the safest were significantly more likely to meet the recommendations for leisure
      time walking. Adolescents from the safest environment achieved 11,024 steps/day
      on average, while those from the least safe environment achieved 9686 steps/day.
      (4) Conclusions: A safe neighborhood environment significantly predicts walking
      activities among girls. Environmental safety improvement can support the active
      transport and better use of leisure time PA.

PMID- 29329278
TI  - T-DNA Tagging-Based Gain-of-Function of OsHKT1;4 Reinforces Na Exclusion from
      Leaves and Stems but Triggers Na Toxicity in Roots of Rice Under Salt Stress.
AB  - The high affinity K+ transporter 1;4 (HKT1;4) in rice (Oryza sativa), which shows
      Na+ selective transport with little K+ transport activity, has been suggested to
      be involved in reducing Na in leaves and stems under salt stress. However,
      detailed physiological roles of OsHKT1;4 remain unknown. Here, we have
      characterized a transfer DNA (T-DNA) insertion mutant line of rice, which
      overexpresses OsHKT1;4, owing to enhancer elements in the T-DNA, to gain an
      insight into the impact of OsHKT1;4 on salt tolerance of rice. The homozygous
      mutant (the O/E line) accumulated significantly lower concentrations of Na in
      young leaves, stems, and seeds than the sibling WT line under salt stress.
      Interestingly, however, the mutation rendered the O/E plants more salt sensitive
      than WT plants. Together with the evaluation of biomass of rice lines,
      rhizosphere acidification assays using a pH indicator bromocresol purple and
      22NaCl tracer experiments have led to an assumption that roots of O/E plants
      suffered heavier damages from Na which excessively accumulated in the root due to
      increased activity of Na+ uptake and Na+ exclusion in the vasculature.
      Implications toward the application of the HKT1-mediated Na+ exclusion system to
      the breeding of salt tolerant crop cultivars will be discussed.

PMID- 29329279
TI  - Diosgenin Protects Rats from Myocardial Inflammatory Injury Induced by Ischemia
      Reperfusion.
AB  - BACKGROUND Diosgenin, a phytosteroid sapogenin, has anti-inflammatory properties
      shown to reduce myocardial ischemia-reperfusion injury (MIRI). However, the
      specific mechanism by which this is achieved is not clear. This study
      investigated the protective effects of diosgenin on myocardial
      ischemia/reperfusion (I/R) and the potential anti-inflammatory mechanisms.
      MATERIAL AND METHODS Healthy adult male SD rats, body weight (b.w.) 250-280 g,
      were used to model ischemia-reperfusion injury (IRI) and were administered
      diosgenin (50 mg/kg and 100 mg/kg b.w.) intragastrically for 4 consecutive weeks
      before surgery. The left anterior descending artery (LAD) was ligated to induce
      myocardial ischemia for 30 min and reperfusion for 30 min, 60 min, and 120 min
      while relevant indicators were detected. RESULTS Both 50 mg and 100 mg diosgenin
      oral administration increased left ventricular developed pressure (LVDP) and
      maximum changing rate of ventricular pressure (+/-dp/dtmax), decreased left
      ventricular end-diastolic pressure (LVEDP), and myocardial enzyme markers. TTC
      staining suggested that diosgenin reduced myocardial infarct size in the rat
      model. Pathological results showed that myocardial ischemia and inflammation were
      alleviated by diosgenin. In addition, the increased expression of tumor necrosis
      factor-alpha (TNF-alpha), interleukin-1 beta (IL-1beta) in serum, and
      myeloperoxidase (MPO) in myocardium were significantly suppressed by diosgenin
      administration. Diosgenin further inhibited the phosphorylation of transcription
      factor NF-kappaB and modulated the expression of downstream inflammatory
      cytokines by regulating the activation of p38-MAPK and JNK pathways. CONCLUSIONS
      Results demonstrate diosgenin plays an anti-inflammatory role in the protection
      of MIRI through regulation of p38-MAPK and JNK pathways and phosphorylation of NF
      kappaB.

PMID- 29329281
TI  - Early career investigator highlight: April.

PMID- 29329280
TI  - Status of HIV Epidemic Control Among Adolescent Girls and Young Women Aged 15-24
      Years - Seven African Countries, 2015-2017.
AB  - In 2016, an estimated 1.5 million females aged 15-24 years were living with human
      immunodeficiency virus (HIV) infection in Eastern and Southern Africa, where the
      prevalence of HIV infection among adolescent girls and young women (3.4%) is more
      than double that for males in the same age range (1.6%) (1). Progress was
      assessed toward the Joint United Nations Programme on HIV/AIDS (UNAIDS) 2020
      targets for adolescent girls and young women in sub-Saharan Africa (90% of those
      with HIV infection aware of their status, 90% of HIV-infected persons aware of
      their status on antiretroviral treatment [ART], and 90% of those on treatment
      virally suppressed [HIV viral load <1,000 HIV RNA copies/mL]) (2) using data from
      recent Population-based HIV Impact Assessment (PHIA) surveys in seven countries.
      The national prevalence of HIV infection in adolescent girls and young women aged
      15-24 years, the percentage who were aware of their status, and among those
      persons who were aware, the percentage who had achieved viral suppression were
      calculated. The target for viral suppression among all persons with HIV infection
      is 73% (the product of 90% x 90% x 90%). Among all seven countries, the
      prevalence of HIV infection among adolescent girls and young women was 3.6%;
      among those in this group, 46.3% reported being aware of their HIV-positive
      status, and 45.0% were virally suppressed. Sustained efforts by national HIV and
      public health programs to diagnose HIV infection in adolescent girls and young
      women as early as possible to ensure rapid initiation of ART should help achieve
      epidemic control among adolescent girls and young women.

PMID- 29329282
TI  - Induction of high-mobility group Box-1 in vitro and in vivo by respiratory
      syncytial virus.
AB  - BackgroundDespite decades that have passed since its discovery, accurate
      biomarkers of respiratory syncytial virus (RSV) disease activity and effective
      therapeutic strategies are still lacking. The high-mobility group box type 1
      (HMGB1) protein has been proposed as a possible link between RSV and immune
      system, but only limited information is currently available to support this
      hypothesis.MethodsExpression of HMGB1 gene and protein was analyzed by
      quantitative PCR, enzyme-linked immunosorbent assay (ELISA), western blot,
      immunocytochemistry, and confocal microscopy in immortalized and primary human
      bronchial epithelial cells, as well as in rat pup lungs. The role of HMGB1 in RSV
      infection was explored using glycyrrhizin, a selective HMGB1 inhibitor.ResultsRSV
      infection strongly induced HMGB1 expression both in vitro and in vivo.
      Glycyrrhizin dose-dependently inhibited HMGB1 upregulation in both RSV-infected
      immortalized and primary human bronchial epithelial cells, and this effect was
      associated with significant reduction of viral replication.ConclusionOur data
      suggest that HMGB1 expression increases during RSV replication. This seems to
      have a critical pathogenic role as its selective inhibition virtually modified
      the infection. These observations provide further insight into the
      pathophysiology of RSV infection and uncover a potential biomarker and
      therapeutic target for the most common respiratory infection of infancy.

PMID- 29329283
TI  - Modeling the assembly order of multimeric heteroprotein complexes.
AB  - Protein-protein interactions are the cornerstone of numerous biological
      processes. Although an increasing number of protein complex structures have been
      determined using experimental methods, relatively fewer studies have been
      performed to determine the assembly order of complexes. In addition to the
      insights into the molecular mechanisms of biological function provided by the
      structure of a complex, knowing the assembly order is important for understanding
      the process of complex formation. Assembly order is also practically useful for
      constructing subcomplexes as a step toward solving the entire complex
      experimentally, designing artificial protein complexes, and developing drugs that
      interrupt a critical step in the complex assembly. There are several experimental
      methods for determining the assembly order of complexes; however, these
      techniques are resource-intensive. Here, we present a computational method that
      predicts the assembly order of protein complexes by building the complex
      structure. The method, named Path-LzerD, uses a multimeric protein docking
      algorithm that assembles a protein complex structure from individual subunit
      structures and predicts assembly order by observing the simulated assembly
      process of the complex. Benchmarked on a dataset of complexes with experimental
      evidence of assembly order, Path-LZerD was successful in predicting the assembly
      pathway for the majority of the cases. Moreover, when compared with a simple
      approach that infers the assembly path from the buried surface area of subunits
      in the native complex, Path-LZerD has the strong advantage that it can be used
      for cases where the complex structure is not known. The path prediction accuracy
      decreased when starting from unbound monomers, particularly for larger complexes
      of five or more subunits, for which only a part of the assembly path was
      correctly identified. As the first method of its kind, Path-LZerD opens a new
      area of computational protein structure modeling and will be an indispensable
      approach for studying protein complexes.

PMID- 29329284
TI  - Identification of an elaborate NK-specific system regulating HLA-C expression.
AB  - The HLA-C gene appears to have evolved in higher primates to serve as a dominant
      source of ligands for the KIR2D family of inhibitory MHC class I receptors. The
      expression of NK cell-intrinsic MHC class I has been shown to regulate the murine
      Ly49 family of MHC class I receptors due to the interaction of these receptors
      with NK cell MHC in cis. However, cis interactions have not been demonstrated for
      the human KIR and HLA proteins. We report the discovery of an elaborate NK cell
      specific system regulating HLA-C expression, indicating an important role for HLA
      C in the development and function of NK cells. A large array of alternative
      transcripts with differences in intron/exon content are generated from an
      upstream NK-specific HLA-C promoter, and exon content varies between HLA-C
      alleles due to SNPs in splice donor/acceptor sites. Skipping of the first coding
      exon of HLA-C generates a subset of untranslatable mRNAs, and the proportion of
      untranslatable HLA-C mRNA decreases as NK cells mature, correlating with
      increased protein expression by mature NK cells. Polymorphism in a key Ets
      binding site of the NK promoter has generated HLA-C alleles that lack significant
      promoter activity, resulting in reduced HLA-C expression and increased functional
      activity. The NK-intrinsic regulation of HLA-C thus represents a novel mechanism
      controlling the lytic activity of NK cells during development.

PMID- 29329285
TI  - A direct interaction of cholesterol with the dopamine transporter prevents its
      out-to-inward transition.
AB  - Monoamine transporters (MATs) carry out neurotransmitter reuptake from the
      synaptic cleft, a key step in neurotransmission, which is targeted in the
      treatment of neurological disorders. Cholesterol (CHOL), a major component of the
      synaptic plasma membrane, has been shown to exhibit a modulatory effect on MATs.
      Recent crystal structures of the dopamine transporter (DAT) revealed the presence
      of two conserved CHOL-like molecules, suggesting a functional protein-CHOL direct
      interaction. Here, we present extensive atomistic molecular dynamics (MD)
      simulations of DAT in an outward-facing conformation. In the absence of bound
      CHOL, DAT undergoes structural changes reflecting early events of dopamine
      transport: transition to an inward-facing conformation. In contrast, in the
      presence of bound CHOL, these conformational changes are inhibited, seemingly by
      an immobilization of the intracellular interface of transmembrane helix 1a and 5
      by CHOL. We also provide evidence, from coarse grain MD simulations that the CHOL
      sites observed in the DAT crystal structures are preserved in all human monoamine
      transporters (dopamine, serotonin and norepinephrine), suggesting that our
      findings might extend to the entire family.

PMID- 29329286
TI  - Is the proportional recovery rule applicable to the lower limb after a first-ever
      ischemic stroke?
AB  - OBJECTIVE: To investigate (a) the applicability of the proportional recovery rule
      of spontaneous neurobiological recovery to motor function of the paretic lower
      extremity (LE); and (b) the presence of fitters and non-fitters of this
      prognostic rule poststroke. When present, the clinical threshold for fitting nor
      non-fitting would be determined, as well as within-subject generalizability to
      the paretic upper extremity (UE). METHODS: Prospective cohort study in which the
      Fugl-Meyer Assessment (FMA)-LE and FMA-UE were measured <72 hours and 6 months
      poststroke. Predicted maximum potential recovery was defined as [FMA-LEmax-FMA
      LEinitial = 34 -FMA-LEinitial]. Hierarchical clustering in 202 first-ever
      ischemic stroke patients distinguished between fitting and not fitting the rule.
      Descriptive statistics determined whether fitters and non-fitters for LE were the
      same persons as for UE. RESULTS: 175 (87%) patients fitted the FMA-LE recovery
      rule. The observed average improvement of the fitters was ~64% of the predicted
      maximum potential recovery. In the non-fitter group, the maximum initial FMA-LE
      score was 13 points. Fifty-one out of 78 patients (~65%) who scored below the
      identified 14-point threshold at baseline fitted the FMA-LE rule. Non-fitters
      were more severely affected than fitters. All non-fitters of the FMA-LE rule did
      also not fit the proportional recovery rule for FMA-UE. CONCLUSIONS: Proportional
      recovery seems to be consistent within subjects across LE and UE motor impairment
      at the hemiplegic side in first-ever ischemic hemispheric stroke subjects. Future
      studies should investigate prospectively distinguishing between fitters and not
      fitters within the subgroup of patients who have initial low FMA-LE scores.
      Subsequently, patients could be stratified based on fitting or not fitting the
      recovery rule as this would impact rehabilitation management and trial design.

PMID- 29329287
TI  - Isolation and complete genome analysis of neurotropic dengue virus serotype 3
      from the cerebrospinal fluid of an encephalitis patient.
AB  - Although neurological manifestations associated with dengue viruses (DENV)
      infection have been reported, there is very limited information on the genetic
      characteristics of neurotropic DENV. Here we describe the isolation and complete
      genome analysis of DENV serotype 3 (DENV-3) from cerebrospinal fluid of an
      encephalitis paediatric patient in Jakarta, Indonesia. Next-generation sequencing
      was employed to deduce the complete genome of the neurotropic DENV-3 isolate.
      Based on complete genome analysis, two unique and nine uncommon amino acid
      changes in the protein coding region were observed in the virus. A phylogenetic
      tree and molecular clock analysis revealed that the neurotropic virus was a
      member of Sumatran-Javan clade of DENV-3 genotype I and shared a common ancestor
      with other isolates from Jakarta around 1998. This is the first report of
      neurotropic DENV-3 complete genome analysis, providing detailed information on
      the genetic characteristics of this virus.

PMID- 29329288
TI  - Soil-transmitted helminth infection, loss of education and cognitive impairment
      in school-aged children: A systematic review and meta-analysis.
AB  - BACKGROUND: Evidence of an adverse influence of soil transmitted helminth (STH)
      infections on cognitive function and educational loss is equivocal. Prior meta
      analyses have focused on randomized controlled trials only and have not
      sufficiently explored the potential for disparate influence of STH infection by
      cognitive domain. We re-examine the hypothesis that STH infection is associated
      with cognitive deficit and educational loss using data from all primary
      epidemiologic studies published between 1992 and 2016. METHODS: Medline, Biosis
      and Web of Science were searched for original studies published in the English
      language. Cognitive function was defined in four domains (learning, memory,
      reaction time and innate intelligence) and educational loss in two domains
      (attendance and scholastic achievement). Pooled effect across studies were
      calculated as standardized mean differences (SMD) to compare cognitive and
      educational measures for STH infected/non-dewormed children versus STH uninfected
      /dewormed children using Review Manager 5.3. Sub-group analyses were implemented
      by study design, risk of bias (ROB) and co-prevalence of Schistosoma species
      infection. Influential studies were excluded in sensitivity analysis to examine
      stability of pooled estimates. FINDINGS: We included 36 studies of 12,920
      children. STH infected/non-dewormed children had small to moderate deficits in
      three domains-learning, memory and intelligence (SMD: -0.44 to -0.27, P<0.01
      0.03) compared to STH-uninfected/dewormed children. There were no differences by
      infection/treatment status for reaction time, school attendance and scholastic
      achievement (SMD: -0.26 to -0.16, P = 0.06-0.19). Heterogeneity of the pooled
      effects in all six domains was high (P<0.01; I2 = 66-99%). Application of outlier
      treatment reduced heterogeneity in learning domain (P = 0.12; I2 = 33%) and
      strengthened STH-related associations in all domains but intelligence (SMD: 
      0.20, P = 0.09). Results varied by study design and ROB. Among experimental
      intervention studies, there was no association between STH treatment and
      educational loss/performance in tests of memory, reaction time and innate
      intelligence (SMD: -0.27 to 0.17, P = 0.18-0.69). Infection-related deficits in
      learning persisted within design/ROB levels (SMD: -0.37 to -52, P<0.01) except
      for pre-vs post intervention design (n = 3 studies, SMD = -0.43, P = 0.47).
      Deficits in memory, reaction time and innate intelligence persisted within
      observational studies (SMD: -0.23 to -0.38, all P<0.01) and high ROB strata (SMD:
      0.37 to -0.83, P = 0.07 to <0.01). Further, in Schistosoma infection co-prevalent
      settings, associations were generally stronger and statistically robust for STH
      related deficits in learning, memory and reaction time tests(SMD:-0.36 to -0.55,
      P = 0.003-0.02). STH-related deficits in school attendance and scholastic
      achievement was noted in low (SMD:-0.57, P = 0.05) and high ROB strata
      respectively. INTERPRETATION: We provide evidence of superior performance in five
      of six educational and cognitive domains assessed for STH uninfected/dewormed
      versus STH infected/not-dewormed school-aged children from helminth endemic
      regions. Cautious interpretation is warranted due to high ROB in some of the
      primary literature and high between study variability in most domains.
      Notwithstanding, this synthesis provides empirical support for a cognitive and
      educational benefit of deworming. The benefit of deworming will be enhanced by
      strategically employing, integrated interventions. Thus, multi-pronged inter
      sectoral strategies that holistically address the environmental and structural
      roots of child cognitive impairment and educational loss in the developing world
      may be needed to fully realize the benefit of mass deworming programs.

PMID- 29329289
TI  - Burkholderia pseudomallei modulates host iron homeostasis to facilitate iron
      availability and intracellular survival.
AB  - BACKGROUND: The control over iron homeostasis is critical in host-pathogen
      interaction. Iron plays not only multiple roles for bacterial growth and
      pathogenicity, but also for modulation of innate immune responses. Hepcidin is a
      key regulator of host iron metabolism triggering degradation of the iron exporter
      ferroportin. Although iron overload in humans is known to increase susceptibility
      to Burkholderia pseudomallei, it is unclear how the pathogen competes with the
      host for the metal during infection. This study aimed to investigate whether B.
      pseudomallei, the causative agent of melioidosis, modulates iron balance and how
      regulation of host cell iron content affects intracellular bacterial
      proliferation. PRINCIPAL FINDINGS: Upon infection of primary macrophages with B.
      pseudomallei, expression of ferroportin was downregulated resulting in higher
      iron availability within macrophages. Exogenous modification of iron export
      function by hepcidin or iron supplementation by ferric ammonium citrate led to
      increased intracellular iron pool stimulating B. pseudomallei growth, whereas the
      iron chelator deferoxamine reduced bacterial survival. Iron-loaded macrophages
      exhibited a lower expression of NADPH oxidase, iNOS, lipocalin 2, cytokines and
      activation of caspase-1. Infection of mice with the pathogen caused a diminished
      hepatic ferroportin expression, higher iron retention in the liver and lower iron
      levels in the serum (hypoferremia). In vivo administration of ferric ammonium
      citrate tended to promote the bacterial growth and inflammatory response, whereas
      limitation of iron availability significantly ameliorated bacterial clearance,
      attenuated serum cytokine levels and improved survival of infected mice.
      CONCLUSIONS: Our data indicate that modulation of the cellular iron balance is
      likely to be a strategy of B. pseudomallei to improve iron acquisition and to
      restrict antibacterial immune effector mechanisms and thereby to promote its
      intracellular growth. Moreover, we provide evidence that changes in host iron
      homeostasis can influence susceptibility to melioidosis, and suggest that iron
      chelating drugs might be an additional therapeutic option.

PMID- 29329290
TI  - MORC2B is essential for meiotic progression and fertility.
AB  - The microrchidia (MORC) family proteins are chromatin-remodelling factors and
      function in diverse biological processes such as DNA damage response and
      transposon silencing. Here, we report that mouse Morc2b encodes a functional germ
      cell-specific member of the MORC protein family. Morc2b arose specifically in the
      rodent lineage through retrotransposition of Morc2a during evolution.
      Inactivation of Morc2b leads to meiotic arrest and sterility in both sexes.
      Morc2b-deficient spermatocytes and oocytes exhibit failures in chromosomal
      synapsis, blockades in meiotic recombination, and increased apoptosis. Loss of
      MORC2B causes mis-regulated expression of meiosis-specific genes. Furthermore, we
      find that MORC2B interacts with MORC2A, its sequence paralogue. Our results
      demonstrate that Morc2b, a relatively recent gene, has evolved an essential role
      in meiosis and fertility.

PMID- 29329294
TI  - A two-stage flow-based intrusion detection model for next-generation networks.
AB  - The next-generation network provides state-of-the-art access-independent services
      over converged mobile and fixed networks. Security in the converged network
      environment is a major challenge. Traditional packet and protocol-based intrusion
      detection techniques cannot be used in next-generation networks due to slow
      throughput, low accuracy and their inability to inspect encrypted payload. An
      alternative solution for protection of next-generation networks is to use network
      flow records for detection of malicious activity in the network traffic. The
      network flow records are independent of access networks and user applications. In
      this paper, we propose a two-stage flow-based intrusion detection system for next
      generation networks. The first stage uses an enhanced unsupervised one-class
      support vector machine which separates malicious flows from normal network
      traffic. The second stage uses a self-organizing map which automatically groups
      malicious flows into different alert clusters. We validated the proposed approach
      on two flow-based datasets and obtained promising results.

PMID- 29329291
TI  - Ovule identity mediated by pre-mRNA processing in Arabidopsis.
AB  - Ovules are fundamental for plant reproduction and crop yield as they are the
      precursors of seeds. Therefore, ovule specification is a critical developmental
      program. In Arabidopsis thaliana, ovule identity is redundantly conferred by the
      homeotic D-class genes SHATTERPROOF1 (SHP1), SHP2 and SEEDSTICK (STK),
      phylogenetically related to the MADS-domain regulatory gene AGAMOUS (AG),
      essential in floral organ specification. Previous studies have shown that the HUA
      PEP activity, comprised of a suite of RNA-binding protein (RBP) encoding genes,
      regulates AG pre-mRNA processing and thus flower patterning and organ identity.
      Here, we report that the HUA-PEP activity additionally governs ovule
      morphogenesis. Accordingly, in severe hua-pep backgrounds ovules transform into
      flower organ-like structures. These homeotic transformations are most likely due
      to the dramatic reduction in SHP1, SHP2 and STK activity. Our molecular and
      genome-wide profiling strategies revealed the accumulation of prematurely
      terminated transcripts of D-class genes in hua-pep mutants and reduced amounts of
      their respective functional messengers, which points to pre-mRNA processing
      misregulation as the origin of the ovule developmental defects in such
      backgrounds. RNA processing and transcription are coordinated by the RNA
      polymerase II (RNAPII) carboxyl-terminal domain (CTD). Our results show that HUA
      PEP activity members can interact with the CTD regulator C-TERMINAL DOMAIN
      PHOSPHATASE-LIKE1 (CPL1), supporting a co-transcriptional mode of action for the
      HUA-PEP activity. Our findings expand the portfolio of reproductive developmental
      programs in which HUA-PEP activity participates, and further substantiates the
      importance of RNA regulatory mechanisms (pre-mRNA co-transcriptional regulation)
      for correct gene expression during plant morphogenesis.

PMID- 29329292
TI  - Transcriptome profiling with focus on potential key genes for wing development
      and evolution in Megaloprepus caerulatus, the damselfly species with the world's
      largest wings.
AB  - The evolution, development and coloration of insect wings remains a puzzling
      subject in evolutionary research. In basal flying insects such as Odonata,
      genomic research regarding bauplan evolution is still rare. Here we focus on the
      world's largest odonate species-the "forest giant" Megaloprepus caerulatus, to
      explore its potential for looking deeper into the development and evolution of
      wings. A recently discovered cryptic species complex in this genus previously
      considered monotypic is characterized by morphological differences in wing shape
      and color patterns. As a first step toward understanding wing pattern divergence
      and pathways involved in adaptation and speciation at the genomic level, we
      present a transcriptome profiling of M. caerulatus using RNA-Seq and compare
      these data with two other odonate species. The de novo transcriptome assembly
      consists of 61,560 high quality transcripts and is approximately 93% complete.
      For almost 75% of the identified transcripts a possible function could be
      assigned: 48,104 transcripts had a hit to an InterPro protein family or domain,
      and 28,653 were mapped to a Gene Ontology term. In particular, we focused on
      genes related to wing development and coloration. The comparison with two other
      species revealed larva-specific genes and a conserved 'core' set of over 8,000
      genes forming orthologous clusters with Ischnura elegans and Ladona fulva. This
      transcriptome may provide a first point of reference for future research in
      odonates addressing questions surrounding the evolution of wing development, wing
      coloration and their role in speciation.

PMID- 29329293
TI  - Cognitive deficits and educational loss in children with schistosome infection-A
      systematic review and meta-analysis.
AB  - BACKGROUND: By means of meta-analysis of information from all relevant
      epidemiologic studies, we examined the hypothesis that Schistosoma infection in
      school-aged children (SAC) is associated with educational loss and cognitive
      deficits. METHODOLOGY/PRINCIPAL FINDINGS: This review was prospectively
      registered in the PROSPERO database (CRD42016040052). Medline, Biosis, and Web of
      Science were searched for studies published before August 2016 that evaluated
      associations between Schistosoma infection and cognitive or educational outcomes.
      Cognitive function was defined in four domains-learning, memory, reaction time,
      and innate intelligence. Educational outcome measures were defined as attendance
      and scholastic achievement. Risk of bias (ROB) was evaluated using the Newcastle
      Ottawa quality assessment scale. Standardized mean differences (SMD) and 95%
      confidence intervals (CI) were calculated to compare cognitive and educational
      measures for Schistosoma infected /not dewormed vs. uninfected/dewormed children.
      Sensitivity analyses by study design, ROB, and sequential exclusion of individual
      studies were implemented. Thirty studies from 14 countries, including 38,992 SAC
      between 5-19 years old, were identified. Compared to uninfected children and
      children dewormed with praziquantel, the presence of Schistosoma infection and/or
      non-dewormed status was associated with deficits in school attendance (SMD = 
      0.36, 95%CI: -0.60, -0.12), scholastic achievement (SMD = -0.58, 95%CI: -0.96, 
      0.20), learning (SMD = -0.39, 95%CI: -0.70, -0.09) and memory (SMD = -0.28,
      95%CI: -0.52, -0.04) tests. By contrast, Schistosoma-infected/non-dewormed and
      uninfected/dewormed children were similar with respect to performance in tests of
      reaction time (SMD = -0.06, 95%CI: -0.42, 0.30) and intelligence (SMD = -0.25,
      95%CI: -0.57, 0.06). Schistosoma infection-associated deficits in educational
      measures were robust among observational studies, but not among interventional
      studies. The significance of infection-associated deficits in scholastic
      achievement was sensitive to ROB. Schistosoma infection-related deficits in
      learning and memory tests were invariant by ROB and study design.
      CONCLUSION/SIGNIFICANCE: Schistosoma infection/non-treatment was significantly
      associated with educational, learning, and memory deficits in SAC. Early
      treatment of children in Schistosoma-endemic regions could potentially mitigate
      these deficits. TRIAL REGISTRATION: ClinicalTrials.gov CRD42016040052.

PMID- 29329295
TI  - Novel signature fatty acid profile of the giant manta ray suggests reliance on an
      uncharacterised mesopelagic food source low in polyunsaturated fatty acids.
AB  - Traditionally, large planktivorous elasmobranchs have been thought to
      predominantly feed on surface zooplankton during daytime hours. However, the
      recent application of molecular methods to examine long-term assimilated diets,
      has revealed that these species likely gain the majority from deeper or demersal
      sources. Signature fatty acid analysis (FA) of muscle tissue was used to examine
      the assimilated diet of the giant manta ray Mobula birostris, and then compared
      with surface zooplankton that was collected during feeding and non-feeding events
      at two aggregation sites off mainland Ecuador. The FA profiles of M. birostris
      and surface zooplankton were markedly different apart from similar proportions of
      arachidonic acid, which suggests daytime surface zooplankton may comprise a small
      amount of dietary intake for M. birostris. The FA profile of M. birostris muscle
      was found to be depleted in polyunsaturated fatty acids, and instead comprised
      high proportions of 18:1omega9 isomers. While 18:1omega9 isomers are not
      explicitly considered dietary FAs, they are commonly found in high proportions in
      deep-sea organisms, including elasmobranch species. Overall, the FA profile of M.
      birostris suggests a diet that is mesopelagic in origin, but many mesopelagic
      zooplankton species also vertically migrate, staying deep during the day and
      moving to shallower waters at night. Here, signature FA analysis is unable to
      resolve the depth at which these putative dietary items were consumed and how
      availability of this prey may drive distribution and movements of this large
      filter-feeder.

PMID- 29329297
TI  - Automated multivariate analysis of multi-sensor data submitted online: Real-time
      environmental monitoring.
AB  - A pilot study demonstrating real-time environmental monitoring with automated
      multivariate analysis of multi-sensor data submitted online has been performed at
      the cabled LoVe Ocean Observatory located at 258 m depth 20 km off the coast of
      Lofoten-Vesteralen, Norway. The major purpose was efficient monitoring of many
      variables simultaneously and early detection of changes and time-trends in the
      overall response pattern before changes were evident in individual variables. The
      pilot study was performed with 12 sensors from May 16 to August 31, 2015. The
      sensors provided data for chlorophyll, turbidity, conductivity, temperature
      (three sensors), salinity (calculated from temperature and conductivity), biomass
      at three different depth intervals (5-50, 50-120, 120-250 m), and current speed
      measured in two directions (east and north) using two sensors covering different
      depths with overlap. A total of 88 variables were monitored, 78 from the two
      current speed sensors. The time-resolution varied, thus the data had to be
      aligned to a common time resolution. After alignment, the data were interpreted
      using principal component analysis (PCA). Initially, a calibration model was
      established using data from May 16 to July 31. The data on current speed from two
      sensors were subject to two separate PCA models and the score vectors from these
      two models were combined with the other 10 variables in a multi-block PCA model.
      The observations from August were projected on the calibration model
      consecutively one at a time and the result was visualized in a score plot.
      Automated PCA of multi-sensor data submitted online is illustrated with an
      attached time-lapse video covering the relative short time period used in the
      pilot study. Methods for statistical validation, and warning and alarm limits are
      described. Redundant sensors enable sensor diagnostics and quality assurance. In
      a future perspective, the concept may be used in integrated environmental
      monitoring.

PMID- 29329296
TI  - Identification and in silico analysis of functional SNPs of human TAGAP protein:
      A comprehensive study.
AB  - Genetic polymorphisms in TAGAP gene have been associated with many diseases
      including rheumatoid arthritis, multiple sclerosis and other autoimmune
      disorders. Identifying functional SNPs in such disease associated genes is an
      uphill task hence before planning larger population study, it is better to
      scrutinize putative functional SNPs. In this study we used various computational
      approaches to identify nsSNPs which are deleterious to the structure and/or
      function of TAGAP protein that might be causing these diseases. Computational
      analysis was performed by five different in silico tools including SIFT, PROVEAN,
      PolyPhen-2, PhD-SNP and SNPs&GO. The study concludes that mutations of Glycine ->
      Glutamic Acid at position 120, Glycine -> Tryptophan at position 141 and Valine 
      > Methionine at position 151 are major mutations in native TAGAP protein which
      might contribute to its malfunction and ultimately causing disease. The study
      also proposed 3D structures of native TAGAP protein and its three mutants. Future
      studies should consider these nsSNPs as main target mutations in various diseases
      involving TAGAP malfunction. This is the first comprehensive study, where TAGAP
      gene variants were analyzed using in silico tools hence will be of great help
      while considering large scale studies and also in developing precision medicines
      for cure of diseases related to these polymorphisms. Furthermore, animal models
      of various autoimmune diseases and having these mutations might be of help in
      exploring their precise roles.

PMID- 29329298
TI  - Single image super-resolution based on approximated Heaviside functions and
      iterative refinement.
AB  - One method of solving the single-image super-resolution problem is to use
      Heaviside functions. This has been done previously by making a binary
      classification of image components as "smooth" and "non-smooth", describing these
      with approximated Heaviside functions (AHFs), and iteration including l1
      regularization. We now introduce a new method in which the binary classification
      of image components is extended to different degrees of smoothness and non
      smoothness, these components being represented by various classes of AHFs. Taking
      into account the sparsity of the non-smooth components, their coefficients are l1
      regularized. In addition, to pick up more image details, the new method uses an
      iterative refinement for the residuals between the original low-resolution input
      and the downsampled resulting image. Experimental results showed that the new
      method is superior to the original AHF method and to four other published
      methods.

PMID- 29329299
TI  - Multi-drug resistant non-typhoidal Salmonella associated with invasive disease in
      western Kenya.
AB  - Non-typhoidal Salmonella (NTS) is a leading cause of bloodstream infections in
      Africa, but the various contributions of host susceptibility versus unique
      pathogen virulence factors are unclear. We used data from a population-based
      surveillance platform (population ~25,000) between 2007-2014 and NTS genome
      sequencing to compare host and pathogen-specific factors between individuals
      presenting with NTS bacteremia and those presenting with NTS diarrhea. Salmonella
      Typhimurium ST313 and Salmonella Enteritidis ST11 were the most common isolates.
      Multi-drug resistant strains of NTS were more commonly isolated from patients
      presenting with NTS bacteremia compared to NTS diarrhea. This relationship was
      observed in patients under age five [aOR = 15.16, 95% CI (2.84-81.05), P =
      0.001], in patients five years and older, [aOR = 6.70 95% CI (2.25-19.89), P =
      0.001], in HIV-uninfected patients, [aOR = 21.61, 95% CI (2.53-185.0), P =
      0.005], and in patients infected with Salmonella serogroup B [aOR = 5.96, 95% CI
      (2.28-15.56), P < 0.001] and serogroup D [aOR = 14.15, 95% CI (1.10-182.7), P =
      0.042]. Thus, multi-drug-resistant NTS was strongly associated with bacteremia
      compared to diarrhea among children and adults. This association was seen in HIV
      uninfected individuals infected with either S. Typhimurium or S. Enteritidis.
      Risk of developing bacteremia from NTS infection may be driven by virulence
      properties of the Salmonella pathogen.

PMID- 29329300
TI  - Symmetric dimeric bisbenzimidazoles DBP(n) reduce methylation of RARB and PTEN
      while significantly increase methylation of rRNA genes in MCF-7 cancer cells.
AB  - BACKGROUND: Hypermethylation is observed in the promoter regions of suppressor
      genes in the tumor cancer cells. Reactivation of these genes by demethylation of
      their promoters is a prospective strategy of the anticancer therapy. Previous
      experiments have shown that symmetric dimeric bisbenzimidazoles DBP(n) are able
      to block DNA methyltransferase activities. It was also found that DBP(n) produces
      a moderate effect on the activation of total gene expression in HeLa-TI
      population containing epigenetically repressed avian sarcoma genome. PRINCIPAL
      FINDINGS: It is shown that DBP(n) are able to penetrate the cellular membranes
      and accumulate in breast carcinoma cell MCF-7, mainly in the mitochondria and in
      the nucleus, excluding the nucleolus. The DBP(n) are non-toxic to the cells and
      have a weak overall demethylation effect on genomic DNA. DBP(n) demethylate the
      promoter regions of the tumor suppressor genes PTEN and RARB. DBP(n) promotes
      expression of the genes RARB, PTEN, CDKN2A, RUNX3, Apaf-1 and APC "silent" in the
      MCF-7 because of the hypermethylation of their promoter regions. Simultaneously
      with the demethylation of the DNA in the nucleus a significant increase in the
      methylation level of rRNA genes in the nucleolus was detected. Increased rDNA
      methylation correlated with a reduction of the rRNA amount in the cells by 20
      30%. It is assumed that during DNA methyltransferase activity inhibition by the
      DBP(n) in the nucleus, the enzyme is sequestered in the nucleolus and provides
      additional methylation of the rDNA that are not shielded by DBP(n).
      CONCLUSIONS/SIGNIFICANCE: It is concluded that DBP (n) are able to accumulate in
      the nucleus (excluding the nucleolus area) and in the mitochondria of cancer
      cells, reducing mitochondrial potential. The DBP (n) induce the demethylation of
      a cancer cell's genome, including the demethylation of the promoters of tumor
      suppressor genes. DBP (n) significantly increase the methylation of ribosomal RNA
      genes in the nucleoli. Therefore the further study of these compounds is needed;
      it could lead to the creation of new anticancer agents.

PMID- 29329301
TI  - Estimated mortality on HIV treatment among active patients and patients lost to
      follow-up in 4 provinces of Zambia: Findings from a multistage sampling-based
      survey.
AB  - BACKGROUND: Survival represents the single most important indicator of successful
      HIV treatment. Routine monitoring fails to capture most deaths. As a result, both
      regional assessments of the impact of HIV services and identification of hotspots
      for improvement efforts are limited. We sought to assess true mortality on
      treatment, characterize the extent under-reporting of mortality in routine health
      information systems in Zambia, and identify drivers of mortality across sites and
      over time using a multistage, regionally representative sampling approach.
      METHODS AND FINDINGS: We enumerated all HIV infected adults on antiretroviral
      therapy (ART) who visited any one of 64 facilities across 4 provinces in Zambia
      during the 24-month period from 1 August 2013 to 31 July 2015. We identified a
      probability sample of patients who were lost to follow-up through selecting
      facilities probability proportional to size and then a simple random sample of
      lost patients. Outcomes among patients lost to follow-up were incorporated into
      survival analysis and multivariate regression through probability weights. Of
      165,464 individuals (64% female, median age 39 years (IQR 33-46), median CD4 201
      cells/mm3 (IQR 111-312), the 2-year cumulative incidence of mortality increased
      from 1.9% (95% CI 1.7%-2.0%) to a corrected rate of 7.0% (95% CI 5.7%-8.4%) (all
      ART users) and from 2.1% (95% CI 1.8%-2.4%) to 8.3% (95% CI 6.1%-10.7%) (new ART
      users). Revised provincial mortality rates ranged from 3-9 times higher than
      naive rates for new ART users and were lowest in Lusaka Province (4.6 per 100
      person-years) and highest in Western Province (8.7 per 100 person-years) after
      correction. Corrected mortality rates varied markedly by clinic, with an IQR of
      3.5 to 7.5 deaths per 100 person-years and a high of 13.4 deaths per 100 person
      years among new ART users, even after adjustment for clinical (e.g., pretherapy
      CD4) and contextual (e.g., province and clinic size) factors. Mortality rates
      (all ART users) were highest year 1 after treatment at 4.6/100 person-years (95%
      CI 3.9-5.5), 2.9/100 person-years (95% CI 2.1-3.9) in year 2, and approximately
      1.6% per year through 8 years on treatment. In multivariate analysis, patient
      level factors including male sex and pretherapy CD4 levels and WHO stage were
      associated with higher mortality among new ART users, while male sex and HIV
      disclosure were associated with mortality among all ART users. In both cases,
      being late (>14 days late for appointment) or lost (>90 days late for an
      appointment) was associated with deaths. We were unable to ascertain the vital
      status of about one-quarter of those lost and selected for tracing and did not
      adjudicate causes of death. CONCLUSIONS: HIV treatment in Zambia is not optimally
      effective. The high and sustained mortality rates and marked under-reporting of
      mortality at the provincial-level and unexplained heterogeneity between regions
      and sites suggest opportunities for the use of corrected mortality rates for
      quality improvement. A regionally representative sampling-based approach can
      bring gaps and opportunities for programs into clear epidemiological focus for
      local and global decision makers.

PMID- 29329302
TI  - Phylogeography and conservation genetics of the rare and relict Bretschneidera
      sinensis (Akaniaceae).
AB  - Bretschneidera sinensis, a class-I protected wild plant in China, is a relic of
      the ancient Tertiary tropical flora endemic to Asia. However, little is known
      about its genetics and phylogeography. To elucidate the current phylogeographic
      patterns and infer the historical population dynamics of B. sinensis, and to make
      recommendations for its conservation, three non-coding regions of chloroplast DNA
      (trnQ-rps16, rps8-rps11, and trnT-trnL) were amplified and sequenced across 256
      individuals from 23 populations of B. sinensis, spanning 10 provinces of China.
      We recognized 13 haplotypes, demonstrating relatively high total haplotype
      diversity (hT = 0.739). Almost all of the variation existed among populations
      (98.09%, P < 0.001), but that within populations was low (1.91%, P < 0.001).
      Strong genetic differentiation was detected among populations (GST = 0.855, P <
      0.001) with limited estimations of seed flow (Nm = 0.09), indicating that
      populations were strongly isolated from one another. According to SAMOVA
      analysis, populations of B. sinensis in China could be divided into five
      geographic groups: (1) eastern Yunnan to western Guangxi; (2) Guizhou-Hunan
      Hubei; (3) central Guangdong; (4) northwestern Guangdong; and (5) the Luoxiao
      Nanling-Wuyi -Yangming Mountain. Network analysis showed that the most ancestral
      haplotypes were located in the first group, i.e., the eastern Yungui Plateau and
      in eastern Yunnan, which is regarded as a putative glacial refugia for B.
      sinensis in China. B. sinensis may have expanded its range eastward from these
      refugia and experienced bottleneck or founder effects in southeastern China.
      Populations in Liping (Guizhou Province), Longsheng (Guangxi Province), Huizhou
      (Guangdong Province), Chongyi (Jiangxi Province), Dong-an (Hunan Province),
      Pingbian (Yunnan Province) and Xinning (Hunan Province) are proposed as the
      priority protection units.

PMID- 29329303
TI  - Efficacy of lateral- versus medial-approach hip joint capsule denervation as
      surgical treatments of the hip joint pain; a neuronal tract tracing study in the
      sheep.
AB  - OBJECTIVE: To evaluate efficacy of denervation of the of the hip joint capsule
      (HJC), as a treatment of hip joint pain. Specifically, we tested the hypothesis
      that HJC denervation will significantly reduce the number of sensory neurons
      innervating the capsule. STUDY DESIGN: Denervation of the HJC from a medial or
      lateral approach was followed by retrograde tracing of sensory neurons
      innervating the capsule. ANIMALS: Twenty adult male sheep (30-40 kg of body
      weight; Polish merino breed) were used in the study. METHODS: The hip joint was
      denervated from medial (n = 5) or lateral (n = 5) surgical approaches.
      Immediately after denervation, the retrograde neural tract tracer Fast Blue (FB)
      was injected into the HJC. An additional ten animals (n = 5 for medial and n = 5
      for lateral approach) received the same treatment without HJC denervation to
      provide the appropriate controls. RESULTS: Results of the study revealed that the
      vast majority of retrogradely labelled sensory neurons innervating the HJC
      originate from fifth lumbar to second sacral dorsal root ganglia. Both the medial
      and the lateral denervations significantly reduced the number of sensory neurons
      innervating the HJC (39.2% and 69.0% reduction respectively). CONCLUSIONS: These
      results show that denervation of the HJC is an effective surgical procedure for
      reduction of the sensory neuronal input to the HJC. Moreover, the lateral
      approach was found to be significantly more effective for reducing sensory
      innervation as compared to the medial one.

PMID- 29329304
TI  - A novel method to test associations between a weighted combination of phenotypes
      and genetic variants.
AB  - Many complex diseases like diabetes, hypertension, metabolic syndrome, et cetera,
      are measured by multiple correlated phenotypes. However, most genome-wide
      association studies (GWAS) focus on one phenotype of interest or study multiple
      phenotypes separately for identifying genetic variants associated with complex
      diseases. Analyzing one phenotype or the related phenotypes separately may lose
      power due to ignoring the information obtained by combining phenotypes, such as
      the correlation between phenotypes. In order to increase statistical power to
      detect genetic variants associated with complex diseases, we develop a novel
      method to test a weighted combination of multiple phenotypes (WCmulP). We perform
      extensive simulation studies as well as real data (COPDGene) analysis to evaluate
      the performance of the proposed method. Our simulation results show that WCmulP
      has correct type I error rates and is either the most powerful test or comparable
      to the most powerful test among the methods we compared. WCmulP also has an
      outstanding performance for identifying single-nucleotide polymorphisms (SNPs)
      associated with COPD-related phenotypes.

PMID- 29329305
TI  - Evaluating the efficacy of switching from lamivudine plus adefovir to tenofovir
      disoproxil fumarate monotherapy in lamivudine-resistant stable hepatitis B
      patients.
AB  - BACKGROUND: The efficacy of switching to tenofovir disoproxil fumarate (TDF)
      monotherapy from lamivudine (LAM) plus adefovir dipivoxil (ADV) combination
      therapy (stable switching) in patients with LAM-resistant chronic hepatitis B
      (CHB) and undetectable hepatitis B virus (HBV) DNA is not clear. METHODS: In this
      non-inferiority trial, patients with LAM-resistant CHB and undetectable serum HBV
      DNA (<20 IU/mL) for >6 months after initiating LAM+ADV combination therapy were
      randomized (1:2) either to continue the combination therapy (LAM+ADV group, n =
      58) or switched to TDF monotherapy (TDF group, n = 111). They were followed-up
      with serum biochemistry tests and HBV DNA measurement at 12-week intervals for 96
      weeks. The primary endpoint of this study was the proportion of patients with
      viral reactivation at week 96. RESULTS: Patients with CHB enrolled in this study
      (n = 169) included 74 patients with compensated liver cirrhosis. In total, 9
      patients (4 in the LAM+ADV group and 5 in the TDF group) dropped-out from the
      study. After a mean follow-up period of 96 weeks, the proportion of HBV
      reactivation observed was 6.8% (4/58) in the LAM+ADV group and 4.5% (5/111) in
      the TDF group by using intention-to-treat analysis (difference, -2.3%; 95% CI, 
      9.84-5.24%). None of the subjects in either group experienced viral reactivation
      based on per protocol analysis. No serious adverse reactions were observed. In
      the subgroup analysis for estimated glomerular filtration rate (eGFR) before and
      after treatment, decreased eGFR was observed only in the TDF group with cirrhosis
      (85.22 vs. 79.83 mL/min/1.73 m2, p = 0.000). CONCLUSIONS: Stable switching to TDF
      monotherapy yielded non-inferior results at 96 weeks compared to the results
      obtained with LAM+ADV combination therapy in patients with LAM-resistant CHB and
      undetectable HBV DNA. However, TDF monotherapy in patients with cirrhosis
      requires close attention with respect to renal function. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT01732367.

PMID- 29329306
TI  - Lifespan extension without fertility reduction following dietary addition of the
      autophagy activator Torin1 in Drosophila melanogaster.
AB  - Autophagy is a highly conserved mechanism for cellular repair that becomes
      progressively down-regulated during normal ageing. Hence, manipulations that
      activate autophagy could increase lifespan. Previous reports show that
      manipulations to the autophagy pathway can result in longevity extension in
      yeast, flies, worms and mammals. Under standard nutrition, autophagy is inhibited
      by the nutrient sensing kinase Target of Rapamycin (TOR). Therefore,
      manipulations of TOR that increase autophagy may offer a mechanism for extending
      lifespan. Ideally, such manipulations should be specific and minimise off-target
      effects, and it is important to discover additional methods for 'clean' lifespan
      manipulation. Here we report an initial study into the effect of up-regulating
      autophagy on lifespan and fertility in Drosophila melanogaster by dietary
      addition of Torin1. Activation of autophagy using this selective TOR inhibitor
      was associated with significantly increased lifespan in both sexes. Torin1
      induced a dose-dependent increase in lifespan in once-mated females. There was no
      evidence of a trade-off between longevity and fecundity or fertility. Torin1-fed
      females exhibited significantly elevated fecundity, but also elevated egg
      infertility, resulting in no net change in overall fertility. This supports the
      idea that lifespan can be extended without trade-offs in fertility and suggest
      that Torin1 may be a useful tool with which to pursue anti-ageing research.

PMID- 29329307
TI  - Response time scores on a reflexive attention task predict a child's inattention
      score from a parent report.
AB  - Compared to sustained attention, only a small proportion of studies examine
      reflexive attention as a component of everyday attention. Understanding the
      significance of reflexive attention to everyday attention may inform better
      treatments for attentional disorders. Children from a general population
      (recruited when they were from 9-16 years old) completed an exogenously-cued task
      measuring the extent to which attention is captured by peripheral cue-target
      conditions. Parents completed a questionnaire reporting their child's day-to-day
      attention. A general linear model indicated that parent-rated inattention
      predicted the increase in response time over baseline when a bright cue preceded
      the target (whether it was valid or invalid) but not when a dim cue preceded the
      target. More attentive children had more pronounced response time increases from
      baseline. Our findings suggest a link between a basic measure of cognition
      (response time difference scores) and parent observations. The findings have
      implications for increased understanding of the role of reflexive attention in
      the everyday attention of children.

PMID- 29329309
TI  - Time series sightability modeling of animal populations.
AB  - Logistic regression models-or "sightability models"-fit to detection/non
      detection data from marked individuals are often used to adjust for visibility
      bias in later detection-only surveys, with population abundance estimated using a
      modified Horvitz-Thompson (mHT) estimator. More recently, a model-based
      alternative for analyzing combined detection/non-detection and detection-only
      data was developed. This approach seemed promising, since it resulted in similar
      estimates as the mHT when applied to data from moose (Alces alces) surveys in
      Minnesota. More importantly, it provided a framework for developing flexible
      models for analyzing multiyear detection-only survey data in combination with
      detection/non-detection data. During initial attempts to extend the model-based
      approach to multiple years of detection-only data, we found that estimates of
      detection probabilities and population abundance were sensitive to the amount of
      detection-only data included in the combined (detection/non-detection and
      detection-only) analysis. Subsequently, we developed a robust hierarchical
      modeling approach where sightability model parameters are informed only by the
      detection/non-detection data, and we used this approach to fit a fixed-effects
      model (FE model) with year-specific parameters and a temporally-smoothed model
      (TS model) that shares information across years via random effects and a temporal
      spline. The abundance estimates from the TS model were more precise, with
      decreased interannual variability relative to the FE model and mHT abundance
      estimates, illustrating the potential benefits from model-based approaches that
      allow information to be shared across years.

PMID- 29329308
TI  - Modeling the effect of boost timing in murine irradiated sporozoite prime-boost
      vaccines.
AB  - Vaccination with radiation-attenuated sporozoites has been shown to induce CD8+ T
      cell-mediated protection against pre-erythrocytic stages of malaria. Empirical
      evidence suggests that successive inoculations often improve the efficacy of this
      type of vaccines. An initial dose (prime) triggers a specific cellular response,
      and subsequent inoculations (boost) amplify this response to create a robust CD8+
      T cell memory. In this work we propose a model to analyze the effect of T cell
      dynamics on the performance of prime-boost vaccines. This model suggests that
      boost doses and timings should be selected according to the T cell response
      elicited by priming. Specifically, boosting during late stages of clonal
      contraction would maximize T cell memory production for vaccines using lower
      doses of irradiated sporozoites. In contrast, single-dose inoculations would be
      indicated for higher vaccine doses. Experimental data have been obtained that
      support theoretical predictions of the model.

PMID- 29329310
TI  - Medication discrepancies across multiple care transitions: A retrospective
      longitudinal cohort study in Italy.
AB  - PURPOSE: Medication discrepancies are defined as unexplained differences among
      regimens across different sites of care. The problem of medication discrepancies
      that occur during the entire care pathway from hospital admission to a local care
      setting discharge (namely all types of settings dedicated to formal care other
      than hospitals) has received little attention in the medical literature. The
      present study aims to (1) determine the prevalence of medication discrepancies
      that occur during the entire care pathway from hospital admission to local care
      setting discharge, (2) describe the discrepancy and medication type, and (3)
      identify potential risk factors for experiencing medication discrepancies in
      patient care transitions. Evidence from an integrated health care system, such as
      the Italian one, may explain results from other studies in different healthcare
      systems. METHODS: A retrospective longitudinal cohort study of patients admitted
      from July 2015 to July 2016 to the Giovanni Bosco Hospital serving Turin, Italy
      and its surrounding territory was performed. Discrepancies were recorded at the
      following four care transitions: T1: Hospital admission; T2: Hospital discharge;
      T3: Admission into local care settings; T4: Discharge from local care settings.
      All evaluations were based on documented regimens and were performed by a team
      (doctor, nurse and pharmacists). RESULTS: Of 366 included patients, 25.68% had at
      least one discrepancy. The most frequent type of discrepancy was from medication
      omission (N = 74; 71.15%). Only discharge from a long-stay care setting (T4) was
      significantly associated with the onset of discrepancies (p = 0.045). When
      considering a lack of adequate documentation, not as missing data but as a
      discrepancy, 43.72% of patients had at least one discrepancy. CONCLUSIONS: This
      study suggests that an integrated health care system, such as Italian system, may
      influence the prevalence of discrepancies, thus highlighting the need for
      structured multidisciplinary and, if possible, computerized medication
      reconciliation to prevent medication discrepancies and improve the quality of
      medical documentation.

PMID- 29329311
TI  - Harmonized clinical trial methodologies for localized cutaneous leishmaniasis and
      potential for extensive network with capacities for clinical evaluation.
AB  - INTRODUCTION: Progress with the treatment of cutaneous leishmaniasis (CL) has
      been hampered by inconsistent methodologies used to assess treatment effects. A
      sizable number of trials conducted over the years has generated only weak
      evidence backing current treatment recommendations, as shown by systematic
      reviews on old-world and new-world CL (OWCL and NWCL). MATERIALS AND METHODS:
      Using a previously published guidance paper on CL treatment trial methodology as
      the reference, consensus was sought on key parameters including core eligibility
      and outcome measures, among OWCL (7 countries, 10 trial sites) and NWCL (7
      countries, 11 trial sites) during two separate meetings. RESULTS: Findings and
      level of consensus within and between OWCL and NWCL sites are presented and
      discussed. In addition, CL trial site characteristics and capacities are
      summarized. CONCLUSIONS: The consensus reached allows standardization of future
      clinical research across OWCL and NWCL sites. We encourage CL researchers to
      adopt and adapt as required the proposed parameters and outcomes in their future
      trials and provide feedback on their experience. The expertise afforded between
      the two sets of clinical sites provides the basis for a powerful consortium with
      potential for extensive, standardized assessment of interventions for CL and
      faster approval of candidate treatments.

PMID- 29329312
TI  - A computational study of the impact of inhomogeneous internodal lengths on
      conduction velocity in myelinated neurons.
AB  - Age-related decreases in the conduction velocity (CV) of action potentials along
      myelinated axons have been linked to morphological changes in the myelin sheath.
      In particular, evidence suggests the presence of segmental demyelination and
      remyelination of axons. In remyelinated segments, the distance between adjacent
      nodes of Ranvier is typically shorter, and myelin sheaths are thinner. Both
      experimental and computational evidence indicates that shortened internodes slows
      CV. In this computational study, we determine the impact of progressive segmental
      demyelination and remyelination, modeled by shorter internodes with thinner
      myelin sheaths interspersed with normal ones, upon the CV. We find that CV
      progressively decreases as the number of remyelinated segments increases, but
      this decrease is greater than one would expect from an estimate of the CV based
      merely upon the number of short and long internodes. We trace the additional
      suppression of the CV to transitions between long and short internodes. Our study
      presents an important consideration for the precise modeling of neural circuits
      with remyelinated neurons.

PMID- 29329313
TI  - Development of a field testing protocol for identifying Deepwater Horizon oil
      spill residues trapped near Gulf of Mexico beaches.
AB  - The Deepwater Horizon (DWH) accident, one of the largest oil spills in U.S.
      history, contaminated several beaches located along the Gulf of Mexico (GOM)
      shoreline. The residues from the spill still continue to be deposited on some of
      these beaches. Methods to track and monitor the fate of these residues require
      approaches that can differentiate the DWH residues from other types of petroleum
      residues. This is because, historically, the crude oil released from sources such
      as natural seeps and anthropogenic discharges have also deposited other types of
      petroleum residues on GOM beaches. Therefore, identifying the origin of these
      residues is critical for developing effective management strategies for
      monitoring the long-term environmental impacts of the DWH oil spill. Advanced
      fingerprinting methods that are currently used for identifying the source of oil
      spill residues require detailed laboratory studies, which can be cost
      prohibitive. Also, most agencies typically use untrained workers or volunteers to
      conduct shoreline monitoring surveys and these worker will not have access to
      advanced laboratory facilities. Furthermore, it is impractical to routinely
      fingerprint large volumes of samples that are collected after a major oil spill
      event, such as the DWH spill. In this study, we propose a simple field testing
      protocol that can identify DWH oil spill residues based on their unique physical
      characteristics. The robustness of the method is demonstrated by testing a
      variety of oil spill samples, and the results are verified by characterizing the
      samples using advanced chemical fingerprinting methods. The verification data
      show that the method yields results that are consistent with the results derived
      from advanced fingerprinting methods. The proposed protocol is a reliable, cost
      effective, practical field approach for differentiating DWH residues from other
      types of petroleum residues.

PMID- 29329314
TI  - Influence of monsoonal winds on chlorophyll-alpha distribution in the Beibu Gulf.
AB  - The influence of seasonal, monsoonal winds on the temporal and spatial
      variability of chlorophyll-a (chl-a) in the Beibu Gulf is studied based on long
      term satellite data of sea surface winds, chl-a concentration and sea surface
      temperature (SST) and in-situ observations for the years from 2002 to 2014. The
      analysis results indicated that under northeasterly monsoonal winds, chl-a
      concentrations were substantially elevated in most area of the Beibu Gulf, with a
      high chl-a concentration (>2 mg m-3) patch extending southwestward from the
      coastal water of the northeastern Gulf, consistent with the winter wind pattern.
      Meanwhile, the spatial distribution of high chl-a concentration is correlated
      with low SST in the northeastern Gulf. In the southern Gulf, there was generally
      low chl-a, except in the coastal waters southwest of Hainan Island. Here, the
      upwelling cold water prevails outside the mouth of the Beibu Gulf, driven by the
      southwesterly monsoonal winds and the runoff from the Changhua River, as implied
      by low observed SST. Correlation analysis indicated the chl-a concentration was
      strongly modulated by wind speed (r = 0.63, p<0.001), particularly in the middle
      of the northern Gulf and southern Hainan Island (r>0.7, p<0.001). Integrated
      analysis also showed that stratification is weak and mixing is strong in winter
      as affected by the high wind speed, which suggests that the wind-induced mixing
      is a dominant mechanism for entrainment of nutrients and the spatial distribution
      of chl-a in winter.

PMID- 29329315
TI  - Role of N-glycosylation in activation of proMMP-9. A molecular dynamics
      simulations study.
AB  - Human matrix metalloproteinase proMMP-9 is secreted as latent zymogen, which
      requires two-steps proteolytic activation. The secreted proMMP-9 is glycosylated
      at two positions: Asn38 and Asn120 located in the prodomain and catalytic domain,
      respectively. It has been demonstrated that glycosylation at Asn120 is required
      for secretion of the enzyme, while the role of Asn38 glycosylation is not well
      understood, but is usually linked to the activation process. One hypothesis
      stated that the Asn38 glycosylation might protect against proteolytic activation.
      However, the activation process occurs with or without the presence of this
      glycosylation. We conducted molecular dynamics (MD) simulations on the
      glycosylated and non-glycosylated proMMP-9 to elucidate the effect of Asn38
      glycosylation on this two-step activation process. The simulation results suggest
      that Asn38 glycosylation does not hinder the activation process directly, but
      induces conformational changes in the vicinity of the first proteolytic region in
      such a way that E59-M60 cleavage is processed before R106-F107. These results
      correlate with analysis provided by Boon et al. and experimental data from Ogata
      et al. who attempted to determine the order of events in activation of proMMP-9.
      Results from additional MD simulations for the model of glycosylated proMMP-9
      bound to galectin-8 N-domain suggest that Gal-8 by interacting with Asn38 glycan
      might further facilitate processing of the first cleavage between E59-M60. Thus,
      our simulation results suggest that both Asn38 glycosylation and interaction with
      Gal-8N may be involved in facilitating and the temporal order of the activation
      process of pro-MMP9. The aim of this report is to provide an inspiration for
      future detailed experiments aimed at explaining the role of N-glycosylation in
      the activation process of prodomain of MMP-9.

PMID- 29329316
TI  - Electroencephalography power and coherence changes with age and motor skill
      development across the first half year of life.
AB  - Existing research in infants has correlated electroencephalography (EEG) measures
      of power and coherence to cognitive development and to locomotor experience, but
      only in infants older than 5 months of age. Our goal was to explore the
      relationship between EEG measures of power and coherence and motor skill
      development in younger infants who are developing reaching skill. Twenty-one
      infants with typical development between 38 and 203 days of age participated.
      Longitudinal EEG recording sessions were recorded in monthly increments, with 3-5
      sessions acquired for 19 participants and 1 session for 2 participants, resulting
      in 71 sessions in total. EEG variables of interest were relative power in the 6-9
      Hz range and coherence between selected electrode pairs. We describe the
      development of the peak in relative power in the 6-9 Hz frequency band of EEG; it
      is not present around 1 month of age and starts to appear across the following
      months. Coherence generally increased in the bilateral frontal-parietal networks,
      while the interhemispheric connectivity in motor cortices generally decreased.
      The results of this relatively small pilot study provide a foundational
      description of neural function changes observed as motor skills are changing
      across the first half year of life. This is a first step in understanding
      experience-dependent plasticity of the infant brain and has the potential to aid
      in the early detection of atypical brain development.

PMID- 29329317
TI  - Oxidative stress caused by activation of NADPH oxidase 4 promotes contrast
      induced acute kidney injury.
AB  - Contrast-induced acute kidney injury (CIAKI) is a leading cause of acute kidney
      injury following radiographic procedures. Intrarenal oxidative stress plays a
      critical role in CIAKI. Nicotinamide adenine dinucleotide 3-phosphate (NADPH)
      oxidases (Noxs) are important sources of reactive oxygen species (ROS). Among the
      various types of Noxs, Nox4 is expressed predominantly in the kidney in rodents.
      Here, we evaluated the role of Nox4 and benefit of Nox4 inhibition on CIAKI using
      in vivo and in vitro models. HK-2 cells were treated with iohexol, with or
      without Nox4 knockdown, or the most specific Nox1/4 inhibitor (GKT137831).
      Effects of Nox4 inhibition on CIAKI mice were examined. Expression of Nox4 in HK
      2 cells was significantly increased following iohexol exposure. Silencing of Nox4
      rescued the production of ROS, downregulated pro-inflammatory markers
      (particularly phospho-p38) implicated in CIAKI, and reduced Bax and caspase 3/7
      activity, which resulted in increased cellular survival in iohexol-treated HK-2
      cells. Pretreatment with GKT137831 replicated these effects by decreasing levels
      of phospho-p38. In a CIAKI mouse model, even though the improvement of plasma
      blood urea nitrogen was unclear, pretreatment with GKT137831 resulted in
      preserved structure, reduced expression of 8-hydroxy-2'-deoxyguanosine (8OHdG)
      and kidney injury molecule-1 (KIM-1), and reduced number of TUNEL (terminal
      deoxynucleotidyl transferase dUTP nick end labeling)-positive cells. These
      results suggest Nox4 as a key source of reactive oxygen species responsible for
      CIAKI and provide a novel potential option for prevention of CIAKI.

PMID- 29329318
TI  - Erythrocyte Inosine triphosphatase activity: A potential biomarker for adverse
      events during combination antiretroviral therapy for HIV.
AB  - The purine analogues tenofovir and abacavir are precursors of potential
      substrates for the enzyme Inosine 5'-triphosphate pyrophosphohydrolase (ITPase).
      Here, we investigated the association of ITPase activity and ITPA genotype with
      the occurrence of adverse events (AEs) during combination antiretroviral therapy
      (cART) for human immunodeficiency virus (HIV) infection. In 393 adult HIV
      seropositive patients, AEs were defined as events that led to stop of cART
      regimen. ITPase activity >=4 mmol IMP/mmol Hb/hour was considered as normal. ITPA
      genotype was determined by testing two ITPA polymorphisms: c.94C>A (p.Pro32Thr,
      rs1127354) and c.124+21A>C (rs7270101). Logistic regression analysis determined
      odds ratios for developing AEs. In tenofovir-containing regimens decreased ITPase
      activity was associated with less AEs (p = 0.01) and longer regimen duration (p =
      0.001). In contrast, in abacavir-containing regimens decreased ITPase activity
      was associated with more AEs (crude p = 0.02) and increased switching of
      medication due to AEs (p = 0.03). ITPA genotype wt/wt was significantly
      associated with an increase in the occurrence of AEs in tenofovir-containing
      regimens. Decreased ITPase activity seems to be protective against occurrence of
      AEs in tenofovir-containing cART, while it is associated with an increase in AEs
      in abacavir-containing regimens.

PMID- 29329319
TI  - Comparative analysis of uranium bioassociation with halophilic bacteria and
      archaea.
AB  - Rock salt represents a potential host rock formation for the final disposal of
      radioactive waste. The interactions between indigenous microorganisms and
      radionuclides, e.g. uranium, need to be investigated to better predict the
      influence of microorganisms on the safety assessment of the repository. Hence,
      the association process of uranium with two microorganisms isolated from rock
      salt was comparatively studied. Brachybacterium sp. G1, which was isolated from
      the German salt dome Gorleben, and Halobacterium noricense DSM15987T, were
      selected as examples of a moderately halophilic bacterium and an extremely
      halophilic archaeon, respectively. The microorganisms exhibited completely
      different association behaviors with uranium. While a pure biosorption process
      took place with Brachybacterium sp. G1 cells, a multistage association process
      occurred with the archaeon. In addition to batch experiments, in situ attenuated
      total reflection Fourier-transform infrared spectroscopy was applied to
      characterize the U(VI) interaction process. Biosorption was identified as the
      dominating process for Brachybacterium sp. G1 with this method. Carboxylic
      functionalities are the dominant interacting groups for the bacterium, whereas
      phosphoryl groups are also involved in U(VI) association by the archaeon H.
      noricense.

PMID- 29329320
TI  - Atypical E2f functions are critical for pancreas polyploidization.
AB  - The presence of polyploid cells in the endocrine and exocrine pancreas has been
      reported for four decades. In rodents, pancreatic polyploidization is initiated
      after weaning and the number of polyploid cells increases with age. Surprisingly
      the molecular regulators and biological functions of polyploidization in the
      pancreas are still unknown. We discovered that atypical E2f activity is essential
      for polyploidization in the pancreas, using an inducible Cre/LoxP approach in new
      born mice to delete ubiquitously the atypical E2f transcription factors, E2f7 and
      E2f8. In contrast to its critical role in embryonic survival, conditional
      deletion of both of both atypical E2fs in newborn mice had no impact on postnatal
      survival and mice lived until old age. However, deficiency of E2f7 or E2f8 alone
      was sufficient to suppress polyploidization in the pancreas and associated with
      only a minor decrease in blood serum levels of glucose, insulin, amylase and
      lipase under 4 hours starvation condition compared to wildtype littermates. In
      mice with fewer pancreatic polyploid cells that were fed ad libitum, no major
      impact on hormones or enzymes levels was observed. In summary, we identified
      atypical E2fs to be essential for polyploidization in the pancreas and discovered
      that postnatal induced loss of both atypical E2fs in many organs is compatible
      with life until old age.

PMID- 29329321
TI  - Impact of lipopolysaccharide-induced acute inflammation on baroreflex-controlled
      sympathetic arterial pressure regulation.
AB  - BACKGROUND: Lipopolysaccharide (LPS) induces acute inflammation, activates
      sympathetic nerve activity (SNA) and alters hemodynamics. Since the arterial
      baroreflex is a negative feedback system to stabilize arterial pressure (AP),
      examining the arterial baroreflex function is a prerequisite to understanding
      complex hemodynamics under LPS challenge. We investigated the impact of LPS
      induced acute inflammation on SNA and AP regulation by performing baroreflex open
      loop analysis. METHODS: Ten anesthetized Sprague-Dawley rats were used. Acute
      inflammation was induced by an intravenous injection of LPS (60 MUg/kg). We
      isolated the carotid sinuses from the systemic circulation and controlled carotid
      sinus pressure (CSP) by a servo-controlled piston pump. We matched CSP to AP to
      establish the baroreflex closed-loop condition, whereas we decoupled CSP from AP
      to establish the baroreflex open-loop condition and changed CSP stepwise to
      evaluate the baroreflex open-loop function. We recorded splanchnic SNA and
      hemodynamic parameters under baroreflex open- and closed-loop conditions at
      baseline and at 60 and 120 min after LPS injection. RESULTS: In the baroreflex
      closed-loop condition, SNA continued to increase after LPS injection, reaching
      three-fold the baseline value at 120 min (baseline: 94.7 +/- 3.6 vs. 120 min:
      283.9 +/- 31.9 a.u.). In contrast, AP increased initially (until 75 min), then
      declined to the baseline level. In the baroreflex open-loop condition, LPS reset
      the neural arc (CSP-SNA relationship) upward to higher SNA, while shifted the
      peripheral arc (SNA-AP relationship) downward at 120 min after the injection. As
      a result, the operating point determined by the intersection between function
      curves of neural arc and peripheral arc showed marked sympatho-excitation without
      substantial changes in AP. CONCLUSIONS: LPS-induced acute inflammation markedly
      increased SNA via resetting of the baroreflex neural arc, and suppressed the
      peripheral arc. The balance between the augmented neural arc and suppressed
      peripheral arc determines SNA and hemodynamics in LPS-induced acute inflammation.

PMID- 29329322
TI  - Methylene-tetrahydrofolate reductase contributes to allergic airway disease.
AB  - RATIONALE: Environmental exposures strongly influence the development and
      progression of asthma. We have previously demonstrated that mice exposed to a
      diet enriched with methyl donors during vulnerable periods of fetal development
      can enhance the heritable risk of allergic airway disease through epigenetic
      changes. There is conflicting evidence on the role of folate (one of the primary
      methyl donors) in modifying allergic airway disease. OBJECTIVES: We hypothesized
      that blocking folate metabolism through the loss of methylene-tetrahydrofolate
      reductase (Mthfr) activity would reduce the allergic airway disease phenotype
      through epigenetic mechanisms. METHODS: Allergic airway disease was induced in
      C57BL/6 and C57BL/6Mthfr-/- mice through house dust mite (HDM) exposure. Airway
      inflammation and airway hyperresponsiveness (AHR) were measured between the two
      groups. Gene expression and methylation profiles were generated for whole lung
      tissue. Disease and molecular outcomes were evaluated in C57BL/6 and C57BL/6Mthfr
      /- mice supplemented with betaine. MEASUREMENTS AND MAIN RESULTS: Loss of Mthfr
      alters single carbon metabolite levels in the lung and serum including elevated
      homocysteine and cystathionine and reduced methionine. HDM-treated C57BL/6Mthfr-/
      mice demonstrated significantly less airway hyperreactivity (AHR) compared to
      HDM-treated C57BL/6 mice. Furthermore, HDM-treated C57BL/6Mthfr-/- mice compared
      to HDM-treated C57BL/6 mice have reduced whole lung lavage (WLL) cellularity,
      eosinophilia, and Il-4/Il-5 cytokine concentrations. Betaine supplementation
      reversed parts of the HDM-induced allergic airway disease that are modified by
      Mthfr loss. 737 genes are differentially expressed and 146 regions are
      differentially methylated in lung tissue from HDM-treated C57BL/6Mthfr-/- mice
      and HDM-treated C57BL/6 mice. Additionally, analysis of methylation/expression
      relationships identified 503 significant correlations. CONCLUSION: Collectively,
      these findings indicate that the loss of folate as a methyl donor is a modifier
      of allergic airway disease, and that epigenetic and expression changes correlate
      with this modification. Further investigation into the mechanisms that drive this
      observation is warranted.

PMID- 29329323
TI  - Stroke risk and outcomes in patients with chronic kidney disease or end-stage
      renal disease: Two nationwide studies.
AB  - BACKGROUND AND AIMS: Because the risk and outcomes of stroke in patients with
      chronic kidney disease (CKD) or end-stage renal disease (ESRD) were unclear, we
      evaluated these risks using a retrospective cohort study and a nested cohort
      study. METHODS: We used Taiwan's National Health Insurance Research Database to
      identify 1378 patients aged >=20 years who had ESRD in 2000-2004. An age- and sex
      matched CKD cohort (n = 5512) and a control cohort (n = 11,024) were selected for
      comparison. Events of incident stroke were considered as outcome during the
      follow-up period in 2000-2013, and we calculated adjusted hazard ratios (HR) and
      95% CIs of stroke associated with CKD or ESRD. We further used matching procedure
      with propensity score to estimate the risk of stroke for control group, CKD
      patients, and EDRD patients. A nested cohort study of 318,638 hospitalized stroke
      patients between 2000 and 2010 also was conducted to analyze the impact of CKD
      and ESRD on post-stroke mortality. RESULTS: Before propensity-score matching, the
      incidences of stroke for controls, CKD patients and ESRD patients were 6.57,
      13.3, and 21.7 per 1000 person-years, respectively. Compared with control group,
      the adjusted HRs of stroke were 1.49 (95% CI, 1.32-1.68) and 2.39 (95% CI, 1.39
      2.87) for people with CKD or ESRD respectively, and were significantly higher in
      both sexes and every age group. After propensity-score matching, the HRs of
      stroke for patients with CKD and ESRD were 1.51 (95% CI 1.24-1.85) and 2.08 (95%
      CI 1.32-3.26), respectively, during the follow-up period. Among hospitalized
      stroke patients, adjusted rate ratio (RR) of post-stroke mortality in CKD and
      ESRD cohorts were 1.44 (95% CI, 1.33-1.56) and 2.62 (95% CI, 2.43-2.82)
      respectively compared with control. CONCLUSIONS: CKD and ESRD patient groups thus
      faced significantly higher risk of stroke and post-stroke mortality. Risk factor
      identification and preventive strategies are needed to minimize stroke risk and
      post-stroke mortality in these vulnerable patient groups.

PMID- 29329325
TI  - Classification of patients with knee osteoarthritis in clinical phenotypes: Data
      from the osteoarthritis initiative.
AB  - OBJECTIVES: The existence of phenotypes has been hypothesized to explain the
      large heterogeneity characterizing the knee osteoarthritis. In a previous
      systematic review of the literature, six main phenotypes were identified: Minimal
      Joint Disease (MJD), Malaligned Biomechanical (MB), Chronic Pain (CP),
      Inflammatory (I), Metabolic Syndrome (MS) and Bone and Cartilage Metabolism
      (BCM). The purpose of this study was to classify a sample of individuals with
      knee osteoarthritis (KOA) into pre-defined groups characterized by specific
      variables that can be linked to different disease mechanisms, and compare these
      phenotypes for demographic and health outcomes. METHODS: 599 patients were
      selected from the OAI database FNIH at 24 months' time to conduct the study. For
      each phenotype, cut offs of key variables were identified matching the results
      from previous studies in the field and the data available for the sample. The
      selection process consisted of 3 steps. At the end of each step, the subjects
      classified were excluded from the further classification stages. Patients meeting
      the criteria for more than one phenotype were classified separately into a
      'complex KOA' group. RESULTS: Phenotype allocation (including complex KOA) was
      successful for 84% of cases with an overlap of 20%. Disease duration was shorter
      in the MJD while the CP phenotype included a larger number of Women (81%). A
      significant effect of phenotypes on WOMAC pain (F = 16.736 p <0.001) and WOMAC
      physical function (F = 14.676, p < 0.001) was identified after controlling for
      disease duration. CONCLUSION: This study signifies the feasibility of a
      classification of KOA subjects in distinct phenotypes based on subgroup-specific
      characteristics.

PMID- 29329324
TI  - Variability and cost implications of three generations of the Roche
      LightCycler(r) 480.
AB  - Real time PCR has become a dominant method for the highly sensitive detection of
      pathogens in clinical material. Real time PCR can generate a fluorescence signal
      by using fluorescence labelled probes, allowing us to detect and semi quantify
      the amount of amplified DNA. Here we test the variability of the detection system
      and cost implications of three different versions of the LightCycler(r) 480
      (LC480), focusing on the intensity of fluorescence and Cq in monoplex and
      multiplex rtPCRs. For gastro-intestinal pathogens there was no correlation
      between the intensity of fluorescence and the Cq value in the different LC480
      types. For probes with the dyes FAMTM, HEXTM, Cy5 and Red610 a higher
      fluorescence intensity was seen in LC480 type II and III compared to LC480 type
      I. After lowering the probe concentration for the Cy5 dye three-fold (from 0.3MUM
      to 0.1MUM) the Cq value remains the same and the intensity of fluorescence
      decreases. For the LC480 type II and III the difference in fluorescence intensity
      was much more extreme. The concentration of the different labelled probes can be
      lowered at least six-fold in LC480 type II and III cyclers while maintaining a
      fluorescence intensity as high as achieved in the LC480 type I with undiluted
      probe. In conclusion, the strength of the fluorescence signal of the
      LightCycler(r) 480 type III is superior to that of LightCycler(r) 480 types I and
      II, allowing the use of lower probe concentrations for all dyes, particularly for
      the dyes Red610 and Cy5. This results in a two thirds reduction in PCR probe
      costs. Switching to these newer machines for real-time PCR can reduce dye
      labelled probe consumption and thus reduce costs significantly.

PMID- 29329326
TI  - Utilization of peptide phage display to investigate hotspots on IL-17A and what
      it means for drug discovery.
AB  - To date, IL-17A antibodies remain the only therapeutic approach to correct the
      abnormal activation of the IL-17A/IL-17R signaling complex. Why is it that
      despite the remarkable success of IL-17 antibodies, there is no small molecule
      antagonist of IL-17A in the clinic? Here we offer a unique approach to address
      this question. In order to understand the interaction of IL-17A with its
      receptor, we combined peptide discovery using phage display with HDX,
      crystallography, and functional assays to map and characterize hot regions that
      contribute to most of the energetics of the IL-17A/IL-17R interaction. These
      functional maps are proposed to serve as a guide to aid in the development of
      small molecules that bind to IL-17A and block its interaction with IL-17RA.

PMID- 29329327
TI  - Selection of housekeeping genes and demonstration of RNAi in cotton leafhopper,
      Amrasca biguttula biguttula (Ishida).
AB  - Amrasca biguttula biguttula (Ishida) commonly known as cotton leafhopper is a
      severe pest of cotton and okra. Not much is known on this insect at molecular
      level due to lack of genomic and transcriptomic data. To prepare for functional
      genomic studies in this insect, we evaluated 15 common housekeeping genes (Tub, B
      Tub, EF alpha, GADPH, UbiCF, RP13, Ubiq, G3PD, VATPase, Actin, 18s, 28s, TATA,
      ETF, SOD and Cytolytic actin) during different developmental stages and under
      starvation stress. We selected early (1st and 2nd), late (3rd and 4th) stage
      nymphs and adults for identification of stable housekeeping genes using geNorm,
      NormFinder, BestKeeper and RefFinder software. Based on the different algorithms,
      RP13 and VATPase are identified as the most suitable reference genes for
      quantification of gene expression by reverse transcriptase quantitative PCR (RT
      qPCR). Based on RefFinder which comprehended the results of three algorithms,
      RP13 in adults, Tubulin (Tub) in late nymphs, 28S in early nymph and UbiCF under
      starvation stress were identified as the most stable genes. We also developed
      methods for feeding double-stranded RNA (dsRNA) incorporated in the diet. Feeding
      dsRNA targeting Snf7, IAP, AQP1, and VATPase caused 56.17-77.12% knockdown of
      targeted genes compared to control and 16 to 48% mortality of treated insects
      when compared to control.

PMID- 29329328
TI  - Early occurrence of inspiratory muscle weakness in Parkinson's disease.
AB  - INTRODUCTION: In Parkinson's disease (PD), respiratory insufficiency (including
      functional and muscle disorders) can impact dysarthria and swallowing. Most
      studies of this topic have been performed retrospectively in populations of
      patients with advanced PD. The objective of the present study was to characterize
      lung function (under off-drug conditions) in early-stage PD patients at baseline
      and then again two years later. METHODS: Forty-one early-stage PD patients (mean
      +/- SD age: 61.7 +/- 7.7; mean +/- SD disease duration: 1.9 +/- 1.7 years) were
      prospectively enrolled and compared with 36 age-matched healthy controls.
      Neurological evaluations and pulmonary function testing were performed in the off
      drug condition at the inclusion visit and then two years later. RESULTS:
      Pulmonary function testing did not reveal any restrictive or obstructive
      disorders; at baseline, inspiratory muscle weakness was the only abnormality
      observed in the PD group (in 53.7% of the patients, vs. 25% in controls; p =
      0.0105). The PD patients had a lower mean maximal inspiratory mouth pressure than
      controls and a lower sniff nasal inspiratory pressure. Two years after the
      initiation of chronic treatment with antiparkinsonian medications, the maximal
      inspiratory mouth pressure and the sniff nasal inspiratory pressure tended to be
      higher. Lastly, overall motor outcomes were not significantly worse in patients
      with inspiratory muscle weakness than in patients without inspiratory muscle
      weakness. CONCLUSION: Inspiratory muscle weakness seems to be common in patients
      with early-stage PD, and was seen to be stable over a two-year period. Additional
      long-term follow-up studies are required to specify the impact of this new
      feature of PD.

PMID- 29329329
TI  - Prevalence, risk factors and molecular evaluation of hepatitis E virus infection
      among pregnant women resident in the northern shores of Persian Gulf, Iran.
AB  - BACKGROUND: Although Iran is reported to be an endemic country for hepatitis E
      virus (HEV), data on the prevalence of HEV infection among pregnant women are
      scarce and the epidemiology of HEV is unknown in most parts of the country.
      Therefore, this study was conducted to elucidate the prevalence, risk factors and
      genotypic pattern of HEV infection among pregnant women resident in the northern
      shores of Persian Gulf. This is the first report on the epidemiology of HEV
      infection among pregnant women in this territory. METHODS: From October 2016 to
      May 2017, 1331 pregnant women participated in this study. The mean age +/- SD of
      participants was 27.93+/-5.7 years with a range of 14-45 years. Serum samples of
      pregnant women were screened for the presence of anti-HEV total antibodies, anti
      HEV IgG and anti-HEV IgM using commercially available ELISA kits (DIA.PRO, Milan,
      Italy). All anti-HEV IgG and anti-HEV IgM positive samples were tested for HEV
      RNA using two independent reverse transcriptase polymerase chain reaction (RT
      PCR) assays, targeting ORF2 and ORF3 of HEV genome. In addition, 92 anti-HEV
      seronegative samples as well as 50 pooled seronegative samples were evaluated by
      two independent RT-PCR assays for validation of results. RESULTS: Of the 1331
      pregnant women, 84 women (6.3%, 95% CI: 5.1%-7.7%) were positive for anti-HEV
      antibodies, of which 83 women had anti-HEV IgG, and 11 women (0.83%, 95% CI:
      0.47%-1.47%) had anti-HEV IgM. The highest rate of HEV seroprevalence was
      observed among Afghan immigrants (68.0%), uneducated pregnant women (46.51%) and
      those residents in Bushehr city (8.75%). All anti-HEV IgG and/or IgM positive
      samples were found to be negative for HEV RNA. In addition, all of the evaluated
      anti-HEV seronegative samples were negative for HEV RNA. HEV seropositivity among
      pregnant women was statistically associated with age, ethnicity, place of
      residence, number of pregnancies, and level of education. So that, low education
      levels, Afghan, residence in Bushehr city, age group >34 years, and more parities
      were risk factors for exposure to HEV. In contrast, HEV seropositivity was not
      associated with stage of gestation, history of abortion, and time of sampling.
      CONCLUSION: The northern shores of Persian Gulf in Iran, with HEV seroprevalence
      of 6.3%, can be classified as an endemic geographical region for hepatitis E, and
      residents of Bushehr city, Afghan immigrants and uneducated women are the main at
      risk populations in this territory.

PMID- 29329330
TI  - Obesity and abnormal glucose tolerance in offspring of diabetic mothers: A
      systematic review and meta-analysis.
AB  - BACKGROUND: Rising prevalence of childhood obesity and type 2 diabetes mellitus
      (T2DM) is an emerging public health issue. OBJECTIVES: To investigate the
      association of maternal hyperglycemia exposure during pregnancy with obesity and
      abnormal glucose tolerance in offspring, and the age at occurrence. METHODS: We
      searched MEDLINE and EMBASE for observational studies on obesity and diabetes in
      offspring of diabetic mothers (gestational diabetes mellitus (GDM), type 1
      diabetes mellitus (T1DM) and T2DM), and those on non-diabetic mothers. We
      performed fixed effect meta-analysis for all studies except when heterogeneity
      was detected. The quality of studies was evaluated using the Risk of Bias
      Assessment Tool for Nonrandomized Studies (RoBANS). RESULTS: Twenty observational
      studies were included involving a total of 26,509 children. Offspring of GDM
      mother had higher BMI z-score in childhood (pooled MD: 0.14, 95%CI: 0.04-0.24,
      seven studies, 21,691children, low quality of evidence). Offspring of T1DM
      mothers had higher BMI z-score from prepubertal to adolescent (pooled MD: 0.35,
      95% CI: 0.13-0.58, three studies, 844 children, low quality of evidence) compared
      with control. After adjustment for maternal pre-pregnancy BMI, this association
      remained in offspring of T1DM, but disappeared in those of GDM mothers. Offspring
      of GDM mother had higher 2-hour plasma glucose from prepubertal to early
      adulthood (pooled MD: 0.43 mmol/L, 95% CI: 0.18-0.69, five studies, 890
      children), while those of T1DM mothers had higher rate of T2DM in 2-5 years old
      to early adulthood (pooled odds ratio [OR], 6.10: 95% CI: 1.23-30.37, two
      studies, 448 children, very low quality of evidence) compared with control. As
      there was only one study with offspring of T2DM mothers, evidence is sparse.
      LIMITATIONS: Only observational studies were included, with a few adequately
      adjusted for covariables. CONCLUSIONS: Exposure to maternal hyperglycemia was
      associated with offspring obesity and abnormal glucose tolerance especially in
      offspring of T1DM mothers, but the evidence relies on observational studies with
      low quality of evidence only.

PMID- 29329331
TI  - Performance similarities predict collective benefits in dyadic and triadic joint
      visual search.
AB  - When humans perform tasks together, they may reach a higher performance in
      comparison to the best member of a group (i.e., a collective benefit). Earlier
      research showed that interindividual performance similarities predict collective
      benefits for several joint tasks. Yet, researchers did not test whether this is
      the case for joint visuospatial tasks. Also, researchers did not investigate
      whether dyads and triads reach a collective benefit when they are forbidden to
      exchange any information while performing a visuospatial task. In this study,
      participants performed a joint visual search task either alone, in dyads, or in
      triads, and were not allowed to exchange any information while doing the task. We
      found that dyads reached a collective benefit. Triads did outperform their best
      individual member and dyads-yet, they did not outperform the best dyad pairing
      within the triad. In addition, similarities in performance significantly
      predicted the collective benefit for dyads and triads. Furthermore, we find that
      the dyads' and triads' search performances closely match a simulated performance
      based on the individual search performances, which assumed that members of a
      group act independently. Overall, the present study supports the view that
      performance similarities predict collective benefits in joint tasks. Moreover, it
      provides a basis for future studies to investigate the benefits of exchanging
      information between co-actors in joint visual search tasks.

PMID- 29329332
TI  - Co-delivery of a laminin-111 supplemented hyaluronic acid based hydrogel with
      minced muscle graft in the treatment of volumetric muscle loss injury.
AB  - Minced muscle autografting mediates de novo myofiber regeneration and promotes
      partial recovery of neuromuscular strength after volumetric muscle loss injury
      (VML). A major limitation of this approach is the availability of sufficient
      donor tissue for the treatment of relatively large VMLs without inducing donor
      site morbidity. This study evaluated a laminin-111 supplemented hyaluronic acid
      based hydrogel (HA+LMN) as a putative myoconductive scaffolding to be co
      delivered with minced muscle grafts. In a rat tibialis anterior muscle VML model,
      delivery of a reduced dose of minced muscle graft (50% of VML defect) within
      HA+LMN resulted in a 42% improvement of peak tetanic torque production over
      unrepaired VML affected limbs. However, the improvement in strength was not
      improved compared to a 50% minced graft-only control group. Moreover,
      histological analysis revealed that the improvement in in vivo functional
      capacity mediated by minced grafts in HA+LMN was not accompanied by a
      particularly robust graft mediated regenerative response as determined through
      donor cell tracking of the GFP+ grafting material. Characterization of the
      spatial distribution and density of macrophage and satellite cell populations
      indicated that the combination therapy damps the heightened macrophage response
      while re-establishing satellite content 14 days after VML to a level consistent
      with an endogenously healing ischemia-reperfusion induced muscle injury.
      Moreover, regional analysis revealed that the combination therapy increased
      satellite cell density mostly in the remaining musculature, as opposed to the
      defect area. Based on the results, the following salient conclusions were drawn:
      1) functional recovery mediated by the combination therapy is likely due to a
      superposition of de novo muscle fiber regeneration and augmented repair of muscle
      fibers within the remaining musculature, and 2) The capacity for VML therapies to
      augment regeneration and repair within the remaining musculature may have
      significant clinical impact and warrants further exploration.

PMID- 29329334
TI  - Ensemble learning method for the prediction of new bioactive molecules.
AB  - Pharmacologically active molecules can provide remedies for a range of different
      illnesses and infections. Therefore, the search for such bioactive molecules has
      been an enduring mission. As such, there is a need to employ a more suitable,
      reliable, and robust classification method for enhancing the prediction of the
      existence of new bioactive molecules. In this paper, we adopt a recently
      developed combination of different boosting methods (Adaboost) for the prediction
      of new bioactive molecules. We conducted the research experiments utilizing the
      widely used MDL Drug Data Report (MDDR) database. The proposed boosting method
      generated better results than other machine learning methods. This finding
      suggests that the method is suitable for inclusion among the in silico tools for
      use in cheminformatics, computational chemistry and molecular biology.

PMID- 29329333
TI  - Wide-range screening of anti-inflammatory compounds in tomato using LC-MS and
      elucidating the mechanism of their functions.
AB  - Obesity-induced chronic inflammation is a key factor in type 2 diabetes. A
      vicious cycle involving pro-inflammatory mediators between adipocytes and
      macrophages is a common cause of chronic inflammation in the adipose tissue.
      Tomato is one of the most popular vegetables and is associated with a reduced
      risk of diabetes. However, the molecular mechanism underlying the effect of
      tomato on diabetes is unclear. In this study, we focused on anti-inflammatory
      compounds in tomato. We found that the extract of tomato reduced plasma glucose
      and inflammatory markers in mice. We screened anti-inflammatory fractions in
      tomato using lipopolysaccharide-stimulated RAW264.7 macrophages, and active
      compounds were estimated by liquid chromatography-mass spectrometry over a wide
      range. Surprisingly, a large number of compounds including oxylipin and coumarin
      derivatives were estimated as anti-inflammatory compounds. Especially, 9-oxo
      octadecadienoic acid and daphnetin suppressed pro-inflammatory cytokines in
      RAW264.7 macrophages inhibiting mitogen-activated protein kinase phosphorylation
      and inhibitor of kappa B alpha protein degradation. These findings suggest that
      tomato containing diverse anti-inflammatory compounds ameliorates chronic
      inflammation in obese adipose tissue.

PMID- 29329336
TI  - Effective dispersal and density-dependence in mesophotic macroalgal forests:
      Insights from the Mediterranean species Cystoseira zosteroides.
AB  - Dispersal and recruitment are fundamental processes for population recovery
      following disturbances in sessile species. While both processes are well
      understood for many terrestrial species, they still remain poorly resolved for
      some macroalgal species. Here we experimentally investigated the effective
      dispersal and recruit survival of a mesophotic Mediterranean fucoid, Cystoseira
      zosteroides. In three isolated populations, four sets of settlement collectors
      were placed at increasing distances (from 0 to 10 m) and different orientations
      (North, South, East and West). We observed that effective dispersal was
      restricted to populations' vicinity, with an average of 6.43 m and not further
      than 13.33 m, following a Weibull distribution. During their first year of life,
      survival was up to 50%, but it was lower underneath the adult canopy, suggesting
      a negative density-dependence. To put our results in a broader context we
      compared the effective dispersal of other fucoid and kelp species reported in the
      literature, which confirmed the low dispersal ability of brown algae, in
      particular for fucoids, with an effective dispersal of few meters. Given the
      importance of recruitment for the persistence and recovery of populations after
      disturbances, these results underline the vulnerability of C. zosteroides and
      other fucoid species to escalating threats.

PMID- 29329335
TI  - Immunization with gingipain A hemagglutinin domain of Porphyromonas gingivalis
      induces IgM antibodies binding to malondialdehyde-acetaldehyde modified low
      density lipoprotein.
AB  - Treatment of periodontitis has beneficial effects on systemic inflammation
      markers that relate to progression of atherosclerosis. We aimed to investigate
      whether immunization with A hemagglutinin domain (Rgp44) of Porphyromonas
      gingivalis (Pg), a major etiologic agent of periodontitis, would lead to an
      antibody response cross-reacting with oxidized low-density lipoprotein (OxLDL)
      and how it would affect the progression of atherosclerosis in low-density
      lipoprotein receptor-deficient (LDLR-/-) mice. The data revealed a prominent IgM
      but not IgG response to malondialdehyde-acetaldehyde modified LDL (MAA-LDL) after
      Rgp44 and Pg immunizations, implying that Rgp44/Pg and MAA adducts may share
      cross-reactive epitopes that prompt IgM antibody production and consequently
      confer atheroprotection. A significant negative association was observed between
      atherosclerotic lesion and plasma IgA to Rgp44 in Rgp44 immunized mice,
      supporting further the anti-atherogenic effect of Rgp44 immunization. Plasma IgA
      levels to Rgp44 and to Pg in both Rgp44- and Pg-immunized mice were significantly
      higher than those in saline control, suggesting that IgA to Rgp44 could be a
      surrogate marker of immunization in Pg-immunized mice. Distinct antibody
      responses in plasma IgA levels to MAA-LDL, to Pg lipopolysaccharides (Pg-LPS),
      and to phosphocholine (PCho) were observed after Rgp44 and Pg immunizations,
      indicating that different immunogenic components between Rpg44 and Pg may behave
      differently in regard of their roles in the development of atherosclerosis.
      Immunization with Rgp44 also displayed atheroprotective features in modulation of
      plaque size through association with plasma levels of IL-1alpha whereas whole Pg
      bacteria achieved through regulation of anti-inflammatory cytokine levels of IL-5
      and IL-10. The present study may contribute to refining therapeutic approaches
      aiming to modulate immune responses and inflammatory/anti-inflammatory processes
      in atherosclerosis.

PMID- 29329337
TI  - Mitochondrial DNA ancestry, HPV infection and the risk of cervical cancer in a
      multiethnic population of northeastern Argentina.
AB  - BACKGROUND: Misiones Province in northeastern Argentina is considered to be a
      region with a high prevalence of HPV infection and a high mortality rate due to
      cervical cancer. The reasons for this epidemiological trend are not completely
      understood. To gain insight into this problem, we explored the relationship
      between mitochondrial DNA (mtDNA) ancestry, HPV infection, and development of
      cervical lesions/cancer in women from the city of Posadas in Misiones Province.
      METHODS: Two hundred and sixty-one women, including 92 cases of patients
      diagnosed with cervical lesions and 169 controls, were analyzed. mtDNA ancestry
      was assessed through HVS1 sequencing, while the detection and typing of HPV
      infection was conducted through nested multiplex PCR analysis. Multivariate
      logistic regression was conducted with the resulting data to estimate the odds
      ratios (ORs) adjusted by socio-demographic variables. RESULTS: The study
      participants showed 68.6% Amerindian, 26.1% European and 5.3% African mtDNA
      ancestry, respectively. Multiple regression analysis showed that women with
      African mtDNAs were three times more likely to develop a cervical lesion than
      those with Native American or European mtDNAs [OR of 3.8 (1.2-11.5) for ancestry
      and OR of 3.5 (1.0-12.0) for L haplogroups], although the associated p values
      were not significant when tested under more complex multivariate models. HPV
      infection and the development of cervical lesions/cancer were significant for all
      tested models, with the highest OR values for HPV16 [OR of 24.2 (9.3-62.7)] and
      HPV-58 [OR of 19.0 (2.4-147.7)]. CONCLUSION: HPV infection remains a central risk
      factor for cervical cancer in the Posadas population. The potential role of
      African mtDNA ancestry opens a new avenue for future medical association studies
      in multiethnic populations, and will require further confirmation in large-scale
      studies.

PMID- 29329338
TI  - Pharmacoepidemiological assessment of adherence and influencing co-factors among
      primary open-angle glaucoma patients-An observational cohort study.
AB  - The goal of this study was to assess the adherence of primary open-angle glaucoma
      (POAG) patients to medication, and to determine co-factors influencing adherence,
      using a representative sample of members of the largest German public health
      insurer. The observational cohort study was based on a longitudinal data set from
      2010-2013 and included 250,000 insured persons aged 50 and older with 10,120
      diagnosed POAG patients. Uni- and multivariate analysis was performed to
      investigate several aspects of glaucoma, such as prevalence, adherence, and co
      factors influencing adherence. The main outcome measured adherence with
      prescriptions filled within a year. Multivariate panel regression analysis was
      used to determine the co-factors influencing this adherence. Prevalence of POAG
      was 3.36% [CI: 3.28-3.43%], with 2.91% [CI: 2.81-3.01%] for males and 3.71% [CI:
      3.61-3.81%] for females, increasing with age. The mean level of adherence in
      terms of prescriptions filled was 66.5% [CI: 65.50-67.60%]. The results of this
      analysis revealed a significant influence of age, duration of the disease, care
      need, distance to death, and multimorbidity as co-factors of non-adherence,
      whereas gender had no influence. The analysis provided detailed information about
      POAG health care aspects concerning prevalence and adherence. The most endangered
      risk groups for non-adherence were patients aged 50-59, patients older than 80
      years, patients with a longer duration of POAG, patients with care needs, and
      patients with three or more severe diseases in addition to glaucoma. To know the
      predictors responsible for an increased risk to develop POAG is of importance for
      all persons involved in health care management. Therefore effective strategies to
      increase awareness of patients and medical care personnel about non-adherence and
      the importance of a regular and continuous medication to avoid further nerve
      fiber damage and possible blindness have to be developed.

PMID- 29329341
TI  - Correction: A century of changing flows: Forest management changed flow
      magnitudes and warming advanced the timing of flow in a southwestern US river.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0187875.].

PMID- 29329340
TI  - Cognitive control moderates parenting stress effects on children's diurnal
      cortisol.
AB  - This study investigated associations between parenting stress in parents and self
      reported stress in children with children's diurnal cortisol secretion and
      whether these associations are moderated by known stress-regulating capacities,
      namely child cognitive control. Salivary cortisol concentrations were assessed
      from awakening to evening on two weekend days from 53 6-to-7-year-old children.
      Children completed a cognitive control task and a self-report stress
      questionnaire with an experimenter, while parents completed a parenting stress
      inventory. Hierarchical, linear mixed effects models revealed that higher
      parenting stress was associated with overall reduced cortisol secretion in
      children, and this effect was moderated by cognitive control. Specifically,
      parenting stress was associated with reduced diurnal cortisol levels in children
      with lower cognitive control ability and not in children with higher cognitive
      control ability. There were no effects of self-reported stress in children on
      their cortisol secretion, presumably because 6-to-7-year-old children cannot yet
      self-report on stress experiences. Our results suggest that higher cognitive
      control skills may buffer the effects of parenting stress in parents on their
      children's stress regulation in middle childhood. This could indicate that
      training cognitive control skills in early life could be a target to prevent
      stress-related disorders.

PMID- 29329339
TI  - Accessibility and contribution to glucan masking of natural and genetically
      tagged versions of yeast wall protein 1 of Candida albicans.
AB  - Yeast wall protein 1 (Ywp1) is an abundant glycoprotein of the cell wall of the
      yeast form of Candida albicans, the most prevalent fungal pathogen of humans.
      Antibodies that bind to the polypeptide backbone of isolated Ywp1 show little
      binding to intact yeast cells, presumably because the Ywp1 epitopes are masked by
      the polysaccharides of the mannoproteins that form the outer layer of the cell
      wall. Rare cells do exhibit much greater anti-Ywp1 binding, however, and one of
      these was isolated and characterized. No differences were seen in its Ywp1, but
      it exhibited greater adhesiveness, sensitivity to wall perturbing agents, and
      exposure of its underlying beta-1,3-glucan layer to external antibodies. The
      molecular basis for this greater epitope accessibility has not been determined,
      but has facilitated exploration of how these properties change as a function of
      cell growth and morphology. In addition, previously engineered strains with
      reduced quantities of Ywp1 in their cell walls were also found to have greater
      beta-1,3-glucan exposure, indicating that Ywp1 itself contributes to the masking
      of wall epitopes, which may be important for understanding the anti-adhesive
      effect of Ywp1. Ectopic production of Ywp1 by hyphae, which reduces the
      adhesivity of these filamentous forms of C. albicans, was similarly found to
      reduce exposure of the beta-1,3-glucan in their walls. To monitor Ywp1 in the
      cell wall irrespective of its accessibility, green fluorescent protein (Gfp) was
      genetically inserted into wall-anchored Ywp1 using a bifunctional cassette that
      also allowed production from a single transfection of a soluble, anchor-free
      version. The wall-anchored Ywp1-Gfp-Ywp1 accumulated in the wall of the yeast
      forms but not hyphae, and appeared to have properties similar to native Ywp1,
      including its adhesion-inhibiting effect. Some pseudohyphal walls also detectably
      accumulated this probe. Strains of C. albicans with tandem hemagglutinin (HA)
      epitopes inserted into wall-anchored Ywp1 were previously created by others, and
      were further explored here. As above, rare cells with much greater accessibility
      of the HA epitopes were isolated, and also found to exhibit greater exposure of
      Ywp1 and beta-1,3-glucan. The placement of the HA cassette inhibited the normal N
      glycosylation and propeptide cleavage of Ywp1, but the wall-anchored Ywp1-HA-Ywp1
      still accumulated in the cell wall of yeast forms. Bifunctional transformation
      cassettes were used to additionally tag these molecules with Gfp, generating
      soluble Ywp1-HA-Gfp and wall-anchored Ywp1-HA-Gfp-Ywp1 molecules. The former
      revealed unexpected electrophoretic properties caused by the HA insertion, while
      the latter further highlighted differences between the presence of a tagged Ywp1
      molecule (as revealed by Gfp fluorescence) and its accessibility in the cell wall
      to externally applied antibodies specific for HA, Gfp and Ywp1, with
      accessibility being greatest in the rapidly expanding walls of budding daughter
      cells. These strains and results increase our understanding of cell wall
      properties and how C. albicans masks itself from recognition by the human immune
      system.

PMID- 29329342
TI  - Ternary copper(II) complex: NCI60 screening, toxicity studies, and evaluation of
      efficacy in xenograft models of nasopharyngeal carcinoma.
AB  - Copper(II) ternary complex, [Cu(phen)(C-dmg)(H2O)]NO3 was evaluated against a
      panel of cell lines, tested for in vivo efficacy in nasopharyngeal carcinoma
      xenograft models as well as for toxicity in NOD scid gamma mice. The Cu(II)
      complex displayed broad spectrum cytotoxicity against multiple cancer types,
      including lung, colon, central nervous system, melanoma, ovarian, and prostate
      cancer cell lines in the NCI-60 panel. The Cu(II) complex did not cause
      significant induction of cytochrome P450 (CYP) 3A and 1A enzymes but moderately
      inhibited CYP isoforms 1A2, 2C9, 2C19, 2D6, 2B6, 2C8 and 3A4. The complex
      significantly inhibited tumor growth in nasopharyngeal carcinoma xenograft
      bearing mice models at doses which were well tolerated without causing
      significant or permanent toxic side effects. However, higher doses which resulted
      in better inhibition of tumor growth also resulted in toxicity.

PMID- 29329343
TI  - Effect of freeze-thaw cycling on grain size of biochar.
AB  - Biochar may improve soil hydrology by altering soil porosity, density, hydraulic
      conductivity, and water-holding capacity. These properties are associated with
      the grain size distributions of both soil and biochar, and therefore may change
      as biochar weathers. Here we report how freeze-thaw (F-T) cycling impacts the
      grain size of pine, mesquite, miscanthus, and sewage waste biochars under two
      drainage conditions: undrained (all biochars) and a gravity-drained experiment
      (mesquite biochar only). In the undrained experiment plant biochars showed a
      decrease in median grain size and a change in grain-size distribution consistent
      with the flaking off of thin layers from the biochar surface. Biochar grain size
      distribution changed from unimodal to bimodal, with lower peaks and wider
      distributions. For plant biochars the median grain size decreased by up to 45.8%
      and the grain aspect ratio increased by up to 22.4% after 20 F-T cycles. F-T
      cycling did not change the grain size or aspect ratio of sewage waste biochar. We
      also observed changes in the skeletal density of biochars (maximum increase of
      1.3%), envelope density (maximum decrease of 12.2%), and intraporosity (porosity
      inside particles, maximum increase of 3.2%). In the drained experiment, mesquite
      biochar exhibited a decrease of median grain size (up to 4.2%) and no change of
      aspect ratio after 10 F-T cycles. We also document a positive relationship
      between grain size decrease and initial water content, suggesting that, biochar
      properties that increase water content, like high intraporosity and pore
      connectivity large intrapores, and hydrophilicity, combined with undrained
      conditions and frequent F-T cycles may increase biochar breakdown. The observed
      changes in biochar particle size and shape can be expected to alter hydrologic
      properties, and thus may impact both plant growth and the hydrologic cycle.

PMID- 29329344
TI  - Maintenance of muscle strength retains a normal metabolic cost in simulated
      walking after transtibial limb loss.
AB  - Recent studies on relatively young and fit individuals with limb loss suggest
      that maintaining muscle strength after limb loss may mitigate the high metabolic
      cost of walking typically seen in the larger general limb loss population.
      However, these data are cross-sectional and the muscle strength prior to limb
      loss is unknown, and it is therefore difficult to draw causal inferences on
      changes in strength and gait energetics. Here we used musculoskeletal modeling
      and optimal control simulations to perform a longitudinal study (25 virtual
      "subjects") of the metabolic cost of walking pre- and post-limb loss (unilateral
      transtibial). Simulations of walking were first performed pre-limb loss on a
      model with two intact biological legs, then post-limb loss on a model with a
      unilateral transtibial prosthesis, with a cost function that minimized the
      weighted sum of gait deviations plus metabolic cost. Metabolic costs were
      compared pre- vs. post-limb loss, with systematic modifications to the muscle
      strength and prosthesis type (passive, powered) in the post-limb loss model. The
      metabolic cost prior to limb loss was 3.44+/-0.13 J/m/kg. After limb loss, with a
      passive prosthesis the metabolic cost did not increase above the pre-limb loss
      cost if pre-limb loss muscle strength was maintained (mean -0.6%, p = 0.17, d =
      0.17). With 10% strength loss the metabolic cost with the passive prosthesis
      increased (mean +5.9%, p < 0.001, d = 1.61). With a powered prosthesis, the
      metabolic cost was at or below the pre-limb loss cost for all subjects with
      strength losses of 10% and 20%, but increased for all subjects with strength loss
      of 30% (mean +5.9%, p < 0.001, d = 1.59). The results suggest that maintaining
      muscle strength may prevent an increase in the metabolic cost of walking
      following unilateral transtibial limb loss, and that a gait with minimal
      deviations can be achieved when muscle strength is sufficiently high, even when
      using a passive prosthesis.

PMID- 29329345
TI  - Survival benefit associated with metformin use in inoperable non-small cell lung
      cancer patients with diabetes: A population-based retrospective cohort study.
AB  - OBJECTIVE: To evaluate the effects of metformin use on the survival of inoperable
      non-small cell lung cancer (NSCLC) patients with diabetes using the Taiwanese
      National Health Insurance Research Database. RESEARCH DESIGN AND METHODS: In
      total, 7,620 patients were eligible in this study, among them, 3,578 patients
      were metformin users and 4,042 were non-users. Propensity score matching was used
      to reduce possible confounding factors. In total, 4,182 patients (2,091 matched
      pairs) were included in the matched cohort. Cox proportional hazard model with
      time-dependent covariate were also applied to evaluate the association between
      metformin use and overall survival (OS). RESULTS: A total of 3,578 patients were
      metformin users at the time of diagnosis of NSCLC. Cox proportional hazard model
      with time-dependent covariate revealed that metformin use was associated with a
      significantly longer OS (HR: 0.85, 95.0% CI: 0.80-0.90). The survival benefit of
      metformin use was maintained after propensity score matching at a ratio of 1:1
      (HR: 0.90, 95.0% CI: 0.84-0.97). CONCLUSIONS: Metformin use is associated with
      longer OS in inoperable NSCLC patients with diabetes, suggesting a potential anti
      tumorigenic effect for metformin. Further research is needed to investigate the
      actual role of metformin in the treatment of NSCLC patients with diabetes.

PMID- 29329346
TI  - Evaluation of bloodstream infections, Clostridium difficile infections, and gut
      microbiota in pediatric oncology patients.
AB  - Bloodstream infections (BSI) and Clostridium difficile infections (CDI) in
      pediatric oncology/hematology/bone marrow transplant (BMT) populations are
      associated with significant morbidity and mortality. The objective of this study
      was to explore possible associations between altered microbiome composition and
      the occurrence of BSI and CDI in a cohort of pediatric oncology patients. Stool
      samples were collected from all patients admitted to the pediatric oncology floor
      from Oct.-Dec. 2012. Bacterial profiles from patient stools were determined by
      bacterial 16S rRNA gene profiling. Differences in overall microbiome composition
      were assessed by a permutation-based multivariate analysis of variance test,
      while differences in the relative abundances of specific taxa were assessed by
      Kruskal-Wallis tests. At admission, 9 of 42 patients (21%) were colonized with C.
      difficile, while 6 of 42 (14%) subsequently developed a CDI. Furthermore, 3
      patients (7%) previously had a BSI and 6 patients (14%) subsequently developed a
      BSI. Differences in overall microbiome composition were significantly associated
      with disease type (p = 0.0086), chemotherapy treatment (p = 0.018), BSI following
      admission from any cause (p < 0.0001) or suspected gastrointestinal organisms (p
      = 0.00043). No differences in baseline microbiota were observed between
      individuals who did or did not subsequently develop C. difficile infection.
      Additionally, multiple bacterial groups varied significantly between subjects
      with post-admission BSI compared with no BSI. Our results suggest that
      differences in gut microbiota not only are associated with type of cancer and
      chemotherapy, but may also be predictive of subsequent bloodstream infection.

PMID- 29329348
TI  - Correction: Risk of thromboembolism in cisplatin versus carboplatin-treated
      patients with lung cancer.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0189410.].

PMID- 29329347
TI  - Salivary proteomics of healthy dogs: An in depth catalog.
AB  - OBJECTIVE: To provide an in-depth catalog of the salivary proteome and endogenous
      peptidome of healthy dogs, evaluate proteins and peptides with antimicrobial
      properties, and compare the most common salivary proteins and peptides between
      different breed phylogeny groups. METHODS: 36 healthy dogs without evidence of
      periodontal disease representing four breed phylogeny groups, based upon single
      nucleotide polymorphism haplotypes (ancient, herding/sighthound, and two
      miscellaneous groups). Saliva collected from dogs was pooled by phylogeny group
      and analyzed using nanoscale liquid chromatography-tandem mass spectrometry.
      Resulting tandem mass spectra were compared to databases for identification of
      endogenous peptides and inferred proteins. RESULTS: 2,491 proteins and endogenous
      peptides were found in the saliva of healthy dogs with no periodontal disease.
      All dog phylogeny groups' saliva was rich in proteins and peptides with
      antimicrobial functions. The ancient breeds group was distinct in that it
      contained unique proteins and was missing many proteins and peptides present in
      the other groups. CONCLUSIONS AND CLINICAL RELEVANCE: Using a sophisticated
      nanoscale liquid chromatography-tandem mass spectrometry, we were able to
      identify 10-fold more salivary proteins than previously reported in dogs. Seven
      of the top 10 most abundant proteins or peptides serve immune functions and many
      more with various antimicrobial mechanisms were found. This is the most
      comprehensive analysis of healthy canine saliva to date, and will provide the
      groundwork for future studies analyzing salivary proteins and endogenous peptides
      in disease states.

PMID- 29329349
TI  - Natural wind variability triggered drop in German redispatch volume and costs
      from 2015 to 2016.
AB  - Avoiding dangerous climate change necessitates the decarbonization of electricity
      systems within the next few decades. In Germany, this decarbonization is based on
      an increased exploitation of variable renewable electricity sources such as wind
      and solar power. While system security has remained constantly high, the
      integration of renewables causes additional costs. In 2015, the costs of grid
      management saw an all time high of about ? 1 billion. Despite the addition of
      renewable capacity, these costs dropped substantially in 2016. We thus
      investigate the effect of natural climate variability on grid management costs in
      this study. We show that the decline is triggered by natural wind variability
      focusing on redispatch as a main cost driver. In particular, we find that 2016
      was a weak year in terms of wind generation averages and the occurrence of
      westerly circulation weather types. Moreover, we show that a simple model based
      on the wind generation time series is skillful in detecting redispatch events on
      timescales of weeks and beyond. As a consequence, alterations in annual
      redispatch costs in the order of hundreds of millions of euros need to be
      understood and communicated as a normal feature of the current system due to
      natural wind variability.

PMID- 29329350
TI  - Incidence and risk factors for postoperative lingual neuropraxia following airway
      instrumentation: A retrospective matched case-control study.
AB  - BACKGROUND: Lingual nerve injury or neuropraxia is a rare but potentially serious
      perioperative complication following airway instrumentation during general
      anesthesia. This study explored the the incidence and perioperative risk factors
      for lingual nerve injury in patients receiving laryngeal mask (LMA) or
      endotracheal (ETGA) general anesthesia in a single center experience. METHODS AND
      RESULTS: All surgical patients in our hospital who received LMA or ETGA from 2009
      to 2013 were included, and potential perioperative risk factors were compared.
      Matched controls were randomly selected (in 1:5 ratio) from the same database in
      non-case patients. A total of 36 patients in the records had reported
      experiencing tongue numbness after anesthesia in this study. Compared with the
      non-case surgical population (n = 54314), patients with tongue numbness were
      significantly younger (52.2+/-19.5 vs 42.0+/-14.5; P = 0.002) and reported lower
      ASA physical statuses (2.3+/-0.7 vs 1.6+/-0.6; P<0.001). Patient gender,
      anesthesia technique used, and airway device type (LMA or ETGA) did not differ
      significantly across the two groups. A significantly higher proportion of
      patients underwent operations of the head-and-neck region (38.9 vs 15.6%; P =
      0.002) developed tongue numbness after anesthesia. Multivariate logistic
      regression analysis indicated that head-and-neck operations remained the most
      significant independent risk factor for postoperative lingual nerve injury (AOR
      7.63; 95% CI 2.03-28.70). CONCLUSION: The overall incidence rate of postoperative
      lingual neuropraxy was 0.066% in patients receiving general anesthesia with
      airway device in place. Young and generally healthy patients receiving head-and
      neck operation are at higher risk in developing postoperative lingual neuropraxy.
      Attention should be particularly exercised to reduce the pressure of endotracheal
      tube or laryngeal mask on the tongue during head-and-neck operation to avert the
      occurrence of postoperative lingual neuropraxy.

PMID- 29329351
TI  - Educational gradients in the use of electronic cigarettes and heat-not-burn
      tobacco products in Japan.
AB  - OBJECTIVES: In addition to electronic cigarettes (e-cigarettes), tobacco
      companies have recently begun to sell heat-not-burn tobacco products, Ploom and
      iQOS in Japan. Previous research has reported an inverse association between
      combustible cigarette smoking and educational attainment, but little is known
      about the association for e-cigarettes, especially heat-not-burn tobacco
      products. Our objective was to analyze the relationship between educational
      attainment and e-cigarette and heat-not-burn tobacco use. SETTING: An internet
      survey (randomly sampled research agency panelists) in Japan. PARTICIPANTS: A
      total of 7338 respondents aged 18-69 years in 2015 (3632 men and 3706women).
      PRIMARY MEASURES: Adjusted odds ratios (ORs) of educational attainment for
      current smoking (combustible cigarettes), e-cigarette ever-use, and heat-not-burn
      ever-use were calculated by multivariable logistic regression models using
      covariates including socio-demographic factors. Stratified analyses according to
      smoking status (combustible cigarettes) were additionally performed for e
      cigarette ever-use and heat-not-burn tobacco product ever-use. RESULTS:
      Associations between educational attainment and e-cigarette ever-use or heat-not
      burn tobacco ever-use are not straightforward, although these associations are
      not statistically significant except for one cell. For example, using "graduate
      school" education as a reference category, adjusted ORs for "high school" were
      1.44 (95% confidence interval [CI]: 0.85-2.44) for e-cigarettes ever-use and 0.75
      (95% CI:0.19-2.97) for heat-not-burn tobacco product ever-use. Among current
      smokers, compared with "graduate school" (reference), those with lower
      educational attainment showed 0.6 to 0.7 ORs for e-cigarette ever-use: e.g.,"4
      year university"(OR = 0.54, 95% CI:0.24-1.24) and "high school" (OR = 0.69, 95%
      CI: 0.30-1.60). Among former smokers, lower education indicated higher ORs for
      both e-cigarettes and heat-not-burn tobacco ever-use. CONCLUSIONS: This study
      provides baseline information on educational gradients of e-cigarette and heat
      not-burn tobacco products, ever-use. As heat-not-burn tobacco products are
      increasing their market share in Japan, continuous monitoring of these products
      will be necessary.

PMID- 29329353
TI  - Estimating the responses of winter wheat yields to moisture variations in the
      past 35 years in Jiangsu Province of China.
AB  - Jiangsu is an important agricultural province in China. Winter wheat, as the
      second major grain crop in the province, is greatly affected by moisture
      variations. The objective of this study was to investigate whether there were
      significant trends in changes in the moisture conditions during wheat growing
      seasons over the past decades and how the wheat yields responded to different
      moisture levels by means of a popular drought index, the Standardized
      Precipitation Evapotranspiration Index (SPEI). The study started with a trend
      analysis and quantification of the moisture conditions with the Mann-Kendall test
      and Sen's Slope method, respectively. Then, correlation analysis was carried out
      to determine the relationship between de-trended wheat yields and multi-scalar
      SPEI. Finally, a multivariate panel regression model was established to reveal
      the quantitative yield responses to moisture variations. The results showed that
      the moisture conditions in Jiangsu were generally at a normal level, but this
      century appeared slightly drier in because of the relatively high temperatures.
      There was a significant correlation between short time scale SPEI values and
      wheat yields. Among the three critical stages of wheat development, the SPEI
      values in the late growth stage (April-June) had a closer linkage to the yields
      than in the seedling stage (October-November) and the over-wintering stage
      (December-February). Moreover, the yield responses displayed an asymmetric
      characteristic, namely, moisture excess led to higher yield losses compared to
      moisture deficit in this region. The maximum yield increment could be obtained
      under the moisture level of slight drought according to the 3-month SPEI at the
      late growth stage, while extreme wetting resulted in the most severe yield
      losses. The moisture conditions in the first 15 years of the 21st century were
      more favorable than in the last 20 years of the 20th century for wheat production
      in Jiangsu.

PMID- 29329352
TI  - Interpersonal trauma moderates the relationship between personality factors and
      suicidality of individuals with posttraumatic stress disorder.
AB  - Individuals with posttraumatic stress disorder (PTSD) are more prone to suicidal
      ideation and behavior. While those who have experienced interpersonal trauma
      exhibit more suicidality than those who have experienced non-interpersonal
      trauma, it is unclear how the traumatic effects are related to an individual's
      personality characteristics. This study examined the association between
      interpersonal trauma and personality factors with suicidality, and elucidated the
      moderating role of interpersonal trauma in individuals with PTSD. The study
      included 6,022 participants from the Korean Epidemiologic Catchment Area Study
      2011. The Korean Version of Composite International Diagnostic Interview was used
      for the survey, including the participants' history of suicidality, the traumas
      they have experienced, and their PTSD symptoms. The 11-item version of the Big
      Five Inventory (BFI-11) was used to assess the participants' personality factors.
      76 individuals were diagnosed with PTSD, while 810 had been exposed to trauma but
      were not diagnosed with any DSM-IV mental disorder. Among the individuals with
      PTSD, those who had experienced interpersonal trauma were more likely to have
      suicidal ideation than those who had experienced non-interpersonal trauma (p =
      .020; odds ratio [OR] = 3.643; 95% confidence interval of OR = [1.226, 10.825]).
      High agreeableness and conscientiousness predicted less suicidality in those
      exposed to non-interpersonal trauma, while predicting more suicidality in those
      exposed to interpersonal trauma. Clinicians examining individuals with PTSD
      should pay closer attention to the trauma that they have experienced, as well as
      their personality factors, to provide appropriate treatment.

PMID- 29329354
TI  - Palmitate-induced ER stress and inhibition of protein synthesis in cultured
      myotubes does not require Toll-like receptor 4.
AB  - Saturated fatty acids, such as palmitate, are elevated in metabolically
      dysfunctional conditions like type 2 diabetes mellitus. Palmitate has been shown
      to impair insulin sensitivity and suppress protein synthesis while upregulating
      proteolytic systems in skeletal muscle. Increased sarco/endoplasmic reticulum
      (ER) stress and subsequent activation of the unfolded protein response may
      contribute to the palmitate-induced impairment of muscle protein synthesis. In
      some cell types, ER stress occurs through activation of the Toll-like receptor 4
      (TLR4). Given the link between ER stress and suppression of protein synthesis, we
      investigated whether palmitate induces markers of ER stress and protein synthesis
      by activating TLR4 in cultured mouse C2C12 myotubes. Myotubes were treated with
      vehicle, a TLR4-specific ligand (lipopolysaccharides), palmitate, or a
      combination of palmitate plus a TLR4-specific inhibitor (TAK-242). Inflammatory
      indicators of TLR4 activation (IL-6 and TNFalpha) and markers of ER stress were
      measured, and protein synthesis was assessed using puromycin incorporation.
      Palmitate substantially increased the levels of IL-6, TNF-alpha, CHOP, XBP1s, and
      ATF 4 mRNAs and augmented the levels of CHOP, XBP1s, phospho-PERK and phospho
      eIF2alpha proteins. The TLR4 antagonist attenuated both acute palmitate and LPS
      induced increases in IL-6 and TNFalpha, but did not reduce ER stress signaling
      with either 6 h or 24 h palmitate treatment. Similarly, treating myotubes with
      palmitate for 6 h caused a 43% decline in protein synthesis consistent with an
      increase in phospho-eIF2alpha, and the TLR4 antagonist did not alter these
      responses. These results suggest that palmitate does not induce ER stress through
      TLR4 in muscle, and that palmitate impairs protein synthesis in skeletal muscle
      in part by induction of ER stress.

PMID- 29329357
TI  - Mineralocorticoid Receptor Antagonists Treatment in Resistant Hypertension and
      HFpEF: Evidence and Courage.

PMID- 29329356
TI  - Prognostic factors of noninvasive mechanical ventilation in lung cancer patients
      with acute respiratory failure.
AB  - INTRODUCTION: Few studies have reported outcomes of lung cancer patients with
      acute respiratory failure (RF) using noninvasive positive pressure ventilation
      (NIPPV). The aim of this study was to investigate the prognostic factors in these
      patients. MATERIALS AND METHODS: This retrospective observational study included
      all hospitalized lung cancer patients who received NIPPV for acute RF. It was
      conducted at a tertiary medical center in Taiwan from 2005 to 2010. The primary
      outcome was all cause mortality at 28 days after the initiation of NIPPV.
      Secondary outcomes included all-cause in-hospital mortality, weaning from NIPPV,
      intubation rate, tracheostomy rate, duration of NIPPV, hospital stay and
      intensive care unit stay. RESULTS: The all-cause mortality rate at day 28 of the
      enrolled 58 patients was 39.66%. The 90-day and 1-year mortality rates were
      63.79% and 86.21%, respectively. NIPPV as the first line therapy for RF had
      higher 28-day mortality rate than it used for post-extubation RF (57.6% versus
      16.0%, p<0.05). Independent predictors of mortality at 28 days were progressive
      disease or newly diagnosed lung cancer (OR 14.02 95% CI 1.03-191.59, p = 0.048),
      combined with other organ failure (OR 18.07 95% CI 1.87-172.7, p = 0.012), and
      NIPPV as the first line therapy for RF (OR 35.37 95% CI 3.30-378.68, p = 0.003).
      CONCLUSION: Lung cancer patients using NIPPV with progressive or newly diagnosed
      cancer disease, combined with other organ failure, or NIPPV as the first line
      therapy for respiratory failure have a poor outcome.

PMID- 29329355
TI  - When the brain changes its mind: Oscillatory dynamics of conflict processing and
      response switching in a flanker task during alcohol challenge.
AB  - Despite the subjective experience of being in full and deliberate control of our
      actions, our daily routines rely on a continuous and interactive engagement of
      sensory evaluation and response preparation streams. They unfold automatically
      and unconsciously and are seamlessly integrated with cognitive control which is
      mobilized by stimuli that evoke ambiguity or response conflict. Methods with high
      spatio-temporal sensitivity are needed to provide insight into the interplay
      between automatic and controlled processing. This study used anatomically
      constrained MEG to examine the underlying neural dynamics in a flanker task that
      manipulated S-R incongruity at the stimulus (SI) and response levels (RI). Though
      irrelevant, flankers evoked automatic preparation of motor plans which had to be
      suppressed and reversed following the target presentation on RI trials. Event
      related source power estimates in beta (15-25 Hz) frequency band in the
      sensorimotor cortex tracked motor preparation and response in real time and
      revealed switching from the incorrectly-primed to the correctly-responding
      hemisphere. In contrast, theta oscillations (4-7 Hz) were sensitive to the levels
      of incongruity as the medial and ventrolateral frontal cortices were especially
      activated by response conflict. These two areas are key to cognitive control and
      their integrated contributions to response inhibition and switching were revealed
      by phase-locked co-oscillations. These processes were pharmacologically
      manipulated with a moderate alcohol beverage or a placebo administered to healthy
      social drinkers. Alcohol selectively decreased accuracy to response conflict. It
      strongly attenuated theta oscillations during decision making and partly re
      sculpted relative contributions of the frontal network without affecting the
      motor switching process subserved by beta band. Our results indicate that motor
      preparation is initiated automatically even when counterproductive but that it is
      monitored and regulated by the prefrontal cognitive control processes under
      conflict. They further confirm that the regulative top-down functions are
      particularly vulnerable to alcohol intoxication.

PMID- 29329358
TI  - Modulating Role of Ang1-7 in Control of Blood Pressure and Renal Function in
      AngII-infused Hypertensive Rats.
AB  - BACKGROUND: Indirect evidence suggests that angiotensin 1-7 (Ang1-7) may
      counterbalance prohypertensive actions of angiotensin II (AngII), via activation
      of vascular and/or renal tubular receptors to cause vasodilation and
      natriuresis/diuresis. We examined if Ang1-7 would attenuate the development of
      hypertension, renal vasoconstriction, and decreased natriuresis in AngII-infused
      rats and evaluated the mechanisms involved. METHODS: AngII, alone or with Ang1-7,
      was infused to conscious Sprague-Dawley rats for 13 days and systolic blood
      pressure (SBP) and renal excretion were repeatedly determined. In anesthetized
      rats, acute actions of Ang1-7 and effects of blockade of angiotensin AT1 or Mas
      receptors (candesartan or A-779) were studied. RESULTS: Chronic AngII infusion
      increased SBP from 143 +/- 4 to 195 +/- 6 mm Hg. With Ang1-7 co-infused, SBP
      increased from 133 +/- 5 to 161 +/- 5 mm Hg (increase reduced, P < 0.002);
      concurrent increases in urine flow (V) and sodium excretion (UNaV) were greater.
      In anesthetized normotensive or AngII-induced hypertensive rats, Ang1-7 infusion
      transiently increased mean arterial pressure (MABP), transiently decreased renal
      blood flow (RBF), and caused increases in UNaV and V. In normotensive rats,
      candesartan prevented the Ang1-7-induced increases in MABP and UNaV and the
      decrease in RBF. In anesthetized normotensive, rats intravenous A-779 increased
      MABP (114 +/- 5 to 120 +/- 5 mm Hg, P < 0.03) and urine flow. Surprisingly, these
      changes were not observed with A-779 applied during background Ang1-7 infusion.
      CONCLUSIONS: The results suggest that in AngII-dependent hypertension, Ang1-7
      deficit contributes to sodium and fluid retention and thereby to BP elevation; a
      correction by Ang1-7 infusion seems mediated by AT1 and not Mas receptors.

PMID- 29329360
TI  - Tumor suppressor miR-128-3p inhibits metastasis and epithelial-mesenchymal
      transition by targeting ZEB1 in esophageal squamous-cell cancer.
AB  - MicroRNAs (miRNAs) are some short RNAs that regulate multiple biological
      functions at post-transcriptional levels, such as tumorigenic processes,
      inflammatory lesions and cell apoptosis. Zinc finger E-box binding homeobox
      factor 1 (ZEB1) is a crucial mediator of epithelial-mesenchymal transition (EMT).
      It induces malignant progression of various cancers including human esophageal
      squamous-cell carcinoma (ESCC). In this study, we found that miR-128-3p was
      downregulated in ESCC tissues and cells by using PCR. Moreover, down-regulated
      expression of miR-128-3p was testified to be associated with poor prognosis of
      ESCC patients and might be regarded as an independent prognostic factor. Then, we
      examined the role of miR-128-3p in ESCC cells, and found that miR-128-3p could
      suppress the cell migration and invasion in vitro. Furthermore, ZEB1 was
      confirmed to be a direct target of miR-128-3p by luciferase reporter assay.
      Rescue experiments proved that EMT was regulated by miR-128-3p via suppression of
      ZEB1. Taken all together, we conclude that miR-128-3p suppresses EMT and
      metastasis via ZEB1, and miR-128-3p may be a critical mediator in ESCC.

PMID- 29329359
TI  - Effectiveness of Mass Media Campaigns to Reduce Alcohol Consumption and Harm: A
      Systematic Review.
AB  - Aims: To assess the effectiveness of mass media messages to reduce alcohol
      consumption and related harms using a systematic literature review. Methods:
      Eight databases were searched along with reference lists of eligible studies.
      Studies of any design in any country were included, provided that they evaluated
      a mass media intervention targeting alcohol consumption or related behavioural,
      social cognitive or clinical outcomes. Drink driving interventions and college
      campus campaigns were ineligible. Studies quality were assessed, data were
      extracted and a narrative synthesis conducted. Results: Searches produced 10,212
      results and 24 studies were included in the review. Most campaigns used TV or
      radio in combination with other media channels were conducted in developed
      countries and were of weak quality. There was little evidence of reductions in
      alcohol consumption associated with exposure to campaigns based on 13 studies
      which measured consumption, although most did not state this as a specific aim of
      the campaign. There were some increases in treatment seeking and information
      seeking and mixed evidence of changes in intentions, motivation, beliefs and
      attitudes about alcohol. Campaigns were associated with increases in knowledge
      about alcohol consumption, especially where levels had initially been low. Recall
      of campaigns was high. Conclusion: Mass media health campaigns about alcohol are
      often recalled by individuals, have achieved changes in knowledge, attitudes and
      beliefs about alcohol but there is little evidence of reductions in alcohol
      consumption. Short summary: There is little evidence that mass media campaigns
      have reduced alcohol consumption although most did not state that they aimed to
      do so. Studies show recall of campaigns is high and that they can have an impact
      on knowledge, attitudes and beliefs about alcohol consumption.

PMID- 29329361
TI  - pyHVis3D: visualising molecular simulation deduced H-bond networks in 3D:
      application to T-cell receptor interactions.
AB  - Motivation: Hydrogen bonds (H-bonds) play an essential role for many molecular
      interactions but are also often transient, making visualising them in a flexible
      system challenging. Results: We provide pyHVis3D which allows for an easy to
      interpret 3D visualisation of H-bonds resulting from molecular simulations. We
      demonstrate the power of pyHVis3D by using it to explain the changes in
      experimentally measured binding affinities for three T-cell receptor/peptide/MHC
      complexes and mutants of each of these complexes. Availability and
      implementation: pyHVis3D can be downloaded for free from
      http://opig.stats.ox.ac.uk/resources. Contact: science.bernhard.knapp@gmail.com.
      Supplementary information: Supplementary data are available at Bioinformatics
      online.

PMID- 29329362
TI  - Clostridium butyricum regulates visceral hypersensitivity of irritable bowel
      syndrome by inhibiting colonic mucous low grade inflammation through its action
      on NLRP6.
AB  - Visceral hypersensitivity induced by stress is quite common in irritable bowel
      syndrome (IBS) patients. Probiotics play an important role in reducing visceral
      hypersensitivity in IBS patients. However, the mechanism has not been clearly
      elucidated. In this study, we investigated the role of nod-like receptor pyrin
      domain-containing protein 6 (NLRP6) in Clostridium butyricum-regulated IBS
      induced by stress. Our results showed that NLRP6 was down-regulated in IBS group
      colon tissues. In addition, IL-18, IL-1beta, myeloperoxidase (MPO), d-lactic acid
      (D-LA), and CD172a were up-regulated in the IBS group of colonic mucous. IL-18
      and IL-1beta were also increased after the NLRP6 gene was silenced. Pathological
      score suggested low inflammation of colonic mucous rather than terminal ileum.
      Water-avoidance stress (WAS) showed visceral hypersensitivity to colonic
      distension. However, treatment with Clostridium butyricum reversed these results,
      exerting a beneficial effect. In conclusion, Clostridium butyricum may exert a
      beneficial action on visceral hypersensitivity of IBS by inhibiting low grade
      inflammation of colonic mucous through its action on NLRP6.

PMID- 29329363
TI  - Validity of Teleneuropsychological Assessment in Older Patients with Cognitive
      Disorders.
AB  - Objective: The feasibility and reliability of neuropsychological assessment at a
      distance have been demonstrated, but the validity of this testing medium has not
      been adequately demonstrated. The purpose of this study was to determine the
      ability of video teleconferencing administration of neuropsychological measures
      (teleneuropsychology) in discriminating cognitively impaired from non-impaired
      groups of older adults. It was predicted that measures administered via video
      teleconference would distinguish groups and that the magnitude of differences
      between impaired and non-impaired groups would be similar to group differences
      achieved in traditional administration. Methods: The sample consisted of 197
      older subjects, separated into two groups, with and without cognitive impairment.
      The cognitive impairment group included 78 individuals with clinical diagnoses of
      mild cognitive impairment or Alzheimer's disease. All participants completed
      counterbalanced neuropsychological testing using alternate test forms in both a
      teleneuropsychology and a traditional face-to-face (FTF) administration
      condition. Tests were selected based upon their common use in dementia
      evaluations, brevity, and assessment of multiple cognitive domains. Results from
      FTF and teleneuropsychology test conditions were compared using individual
      repeated measures ANCOVA, controlling for age, education, gender, and depression
      scores. Results: All ANCOVA models revealed significant main effects of group and
      a non-significant interaction between group and administration condition. All
      ANCOVA models revealed non-significant main effects for administration condition,
      except category fluency. Conclusions: Results derived from
      teleneuropsychologically administered tests can distinguish between cognitively
      impaired and non-impaired individuals similar to traditional FTF assessment. This
      adds to the growing teleneuropsychology literature by supporting the validity of
      remote assessments in aging populations.

PMID- 29329365
TI  - A Formative Evaluation of Two FASD Prevention Communication Strategies.
AB  - Aims: To evaluate the feasibility, acceptability and effectiveness of placing
      FASD prevention messages in the women's restrooms of establishments serving
      alcohol in Alaska and the Yukon, regions with high rates of FASD. Methods: Our
      team placed an FASD educational poster, and posters affixed to a pregnancy test
      dispenser, in women's restrooms of bars and restaurants. We compared drinking
      behaviors and knowledge and beliefs about FASD among participants at baseline and
      at follow-up. Results: Respondents consisted of 2132 women who completed a
      baseline survey and 1182 women who completed both a baseline and a follow-up
      survey. Women in both groups showed improvement in knowledge of FASD; the
      dispenser group scored higher than participants in the poster group on the FASD
      Health Belief questions at both baseline and follow-up. Forty-three women learned
      they were pregnant from our pregnancy tests and alcohol consumption among
      pregnant women was lower at follow-up than at baseline. Conclusions: FASD
      prevention messages, particularly paired with pregnancy test dispensers, in the
      women's restrooms of establishments that serve alcohol can effectively promote
      informed alcohol consumption decisions among women who are, or may become,
      pregnant. Short Summary: In this FASD prevention feasibility study, we found that
      FASD prevention messages, particularly paired with pregnancy test dispensers,
      placed in the women's restrooms of establishments that serve alcohol can
      effectively promote informed alcohol consumption decisions among women who are,
      or may become, pregnant.

PMID- 29329366
TI  - Delineating differential regulatory signatures of the human transcriptome in the
      choriodecidua and myometrium at term labor.
AB  - Preterm deliveries remain the leading cause of neonatal morbidity and mortality.
      Current therapies target only myometrial contractions and are largely
      ineffective. As labor involves multiple coordinated events across maternal and
      fetal tissues, identifying fundamental regulatory pathways of normal term labor
      is vital to understanding successful parturition and consequently labor
      pathologies. We aimed to identify transcriptomic signatures of human normal term
      labor of two tissues: in the fetal-facing choriodecidua and the maternal
      myometrium. Microarray transcriptomic data from choriodecidua and myometrium
      following term labor were analyzed for functional hierarchical networks, using
      Cytoscape 2.8.3. Hierarchically high candidates were analyzed for their
      regulatory casual relationships using Ingenuity Pathway Analysis. Selected master
      regulators were then chemically inhibited and effects on downstream targets were
      assessed using real-time quantitative PCR (RT-qPCR). Unbiased network analysis
      identified upstream molecular components in choriodecidua including vimentin,
      TLR4, and TNFSF13B. In the myometrium, candidates included metallothionein 2
      (MT2A), TLR2, and RELB. These master regulators had significant differential gene
      expression during labor, hierarchically high centrality in community cluster
      networks, interactions amongst the labor gene set, and strong causal
      relationships with multiple downstream effects. In vitro experiments highlighted
      MT2A as an effective regulator of labor-associated genes. We have identified
      unique potential regulators of the term labor transcriptome in uterine tissues
      using a robust sequence of unbiased mathematical and literature-based in silico
      analyses. These findings encourage further investigation into the efficacy of
      predicted master regulators in blocking multiple pathways of labor processes
      across maternal and fetal tissues, and their potential as therapeutic approaches.

PMID- 29329364
TI  - Downregulation of Drp1, a fission regulator, is associated with human lung and
      colon cancers.
AB  - Dynamin-related protein 1 (Drp1), a dynamin-related GTPase, is a key regulator of
      mitochondrial fission. Although recent studies have shown that Drp1 plays
      important roles in various important cellular processes, such as maintaining
      proper mitochondrial function, apoptosis and necrosis, the potential involvement
      of Drp1 in cancer development has not been fully addressed. To explore the role
      of Drp1 in cancer, we examined Drp1 levels in various human cancer tissues.
      Tissue array analysis showed that the level of Drp1 was decreased significantly
      in malignant colon and lung cancer tissues, whereas no change in Drp1 was
      observed in breast and prostate tumors. Pairwise comparisons of cancer tissue and
      adjacent normal tissue from colon and lung cancer patients further confirmed
      decreases in Drp1 expression of 75% in colon cancer patients and 78% in lung
      cancer patients. Moreover, Drp1 levels were decreased further with advanced grade
      in both colon and lung cancers, suggesting that loss of Drp1 is associated with
      the progression of human lung and colon cancer. Consistent with this observation,
      knockdown of Drp1 increased cellular migration activity in human lung cancer
      cells and tumor formation in a xenograft tumor model. Taken together, these
      results suggest that the loss of Drp1 expression could contribute to the
      development of human lung and colon cancers.

PMID- 29329367
TI  - Effects of Anodal Transcranial Direct Current Stimulation Over the Ventrolateral
      Prefrontal Cortex on Episodic Memory Formation and Retrieval.
AB  - In the past decade, several studies have investigated the effects of transcranial
      direct current stimulation (tDCS) on episodic memory abilities. However, the
      specific conditions under which tDCS affects memory remain largely unclear. Here,
      we report data from 4 experiments aimed at investigating the effects of anodal
      tDCS over the left ventrolateral prefrontal cortex (VLPFC) on verbal episodic
      memory. We evaluated tDCS-induced effects as a function of time of
      administration, nature of the memory encoding task, and age of the participants.
      A robust enhancement of memory performance was only found when anodal tDCS was
      delivered during intentional memorization. This enhancement was evident in young
      and older adults. tDCS applied during incidental memorization or during retrieval
      did not induce any modulation of memory performance, and memory was unaffected by
      offline administration before encoding or retrieval. These results show that the
      modulation of episodic memory functions by anodal tDCS over the left VLPFC is
      dependent upon the time of administration and the nature of the memory task. The
      findings may help profile the optimal stimulation protocols for
      neurorehabilitation interventions on individuals with memory decline.

PMID- 29329368
TI  - Discovering personalized driver mutation profiles of single samples in cancer by
      network control strategy.
AB  - Motivation: It is a challenging task to discover personalized driver genes that
      provide crucial information on disease risk and drug sensitivity for individual
      patients. However, few methods have been proposed to identify the personalized
      sample driver genes from the cancer omics data due to the lack of samples for
      each individual. To circumvent this problem, here we present a novel single
      sample controller strategy (SCS) to identify personalized driver mutation
      profiles from network controllability perspective. Results: SCS integrates
      mutation data and expression data into a reference molecular network for each
      patient to obtain the driver mutation profiles in a personalized-sample manner.
      This is the first such a computational framework, to bridge the personalized
      driver mutation discovery problem and the structural network controllability
      problem. The key idea of SCS is to detect those mutated genes which can achieve
      the transition from the normal state to the disease state based on each
      individual omics data from network controllability perspective. We widely
      validate the driver mutation profiles of our SCS from three aspects: (i) the
      improved precision for the predicted driver genes in the population compared with
      other driver-focus methods; (ii) the effectiveness for discovering the
      personalized driver genes and (iii) the application to the risk assessment
      through the integration of the driver mutation signature and expression data,
      respectively, across the five distinct benchmarks from The Cancer Genome Atlas.
      In conclusion, our SCS makes efficient and robust personalized driver mutation
      profiles predictions, opening new avenues in personalized medicine and targeted
      cancer therapy. Availability and implementation: The MATLAB-package for our SCS
      is freely available from http://sysbio.sibcb.ac.cn/cb/chenlab/software.htm.
      Contact: zhangsw@nwpu.edu.cn or zengtao@sibs.ac.cn or lnchen@sibs.ac.cn.
      Supplementary information: Supplementary data are available at Bioinformatics
      online.

PMID- 29329369
TI  - A network approach to exploring the functional basis of gene-gene epistatic
      interactions in disease susceptibility.
AB  - Motivation: Individual genetic variants explain only a small fraction of
      heritability in some diseases. Some variants have weak marginal effects on
      disease risk, but their joint effects are significantly stronger when occurring
      together. Most studies on such epistatic interactions have focused on methods for
      identifying the interactions and interpreting individual cases, but few have
      explored their general functional basis. This was due to the lack of a
      comprehensive list of epistatic interactions and uncertainties in associating
      variants to genes. Results: We conducted a large-scale survey of published
      research articles to compile the first comprehensive list of epistatic
      interactions in human diseases with detailed annotations. We used various methods
      to associate these variants to genes to ensure robustness. We found that these
      genes are significantly more connected in protein interaction networks, are more
      co-expressed and participate more often in the same pathways. We demonstrate
      using the list to discover novel disease pathways. Contact:
      kevinyip@cse.cuhk.edu.hk. Supplementary information: Supplementary data are
      available at Bioinformatics online.

PMID- 29329370
TI  - Defining Normal Parameters for the Male Nipple-Areola Complex: A Prospective
      Observational Study and Recommendations for Placement on the Chest Wall.
AB  - Background: The nipple-areola complex (NAC) is important aesthetically and
      functionally for both sexes. Methods for positioning the NAC in males are less
      well established in the literature compared to females but are just as important.
      Objectives: This study aims to determine the normal parameters for the male NAC,
      to review literature, and to present a reliable method for preoperative
      placement. Methods: Normal male patients, with no prior chest wall conditions,
      were prospectively recruited to participate. General demographics and chest wall
      dimensions were recorded-sternal notch to nipple (SNND), internipple (IND),
      anterior axillary folds distances (AFD), NAC, and chest circumference were
      measured. Comparisons were made using t test and ANOVA. Results: One hundred and
      fifty-eight patients were recruited (age range, 18-90 years); mostly (86.7%) with
      normal or overweight BMI. The IND averaged 249.4 mm, the SNND averaged 204.2 mm,
      and the AFD averaged 383.8 mm. Areola diameter averaged 26.6 mm and for the
      nipple, 6.9 mm. The IND:AFD ratio was 0.65. There was no statistical difference
      in the IND:AFD ratio, SNND, or NAC parameters comparing different ethnic groups.
      The SNND increased with greater BMI (P <= 0.001). Using these data, we suggest
      ideal NAC dimensions and devised a simple method for positioning of the NAC on
      the male chest wall. Conclusions: This is the largest study, with the widest
      range in age and BMI, to date on this topic. Although fewer men than women
      undergo surgery to the breast, there is a growing awareness for enhancing the
      appearance of the male chest wall. Level of Evidence 4: 

PMID- 29329372
TI  - Enrichment analysis with EpiAnnotator.
AB  - Motivation: Deciphering relevant biological insights from epigenomic data can be
      a challenging task. One commonly used approach is to perform enrichment analysis.
      However, finding, downloading and using the publicly available functional
      annotations require time, programming skills and IT infrastructure. Here we
      describe the online tool EpiAnnotator for performing enrichment analyses on
      epigenomic data in a fast and user-friendly way. Results: EpiAnnotator is an R
      Package accompanied by a web interface. It contains regularly updated annotations
      from 4 public databases: Blueprint, RoadMap, GENCODE and the UCSC Genome Browser.
      Annotations are hosted locally or in a server environment and automatically
      updated by scripts of our own design. Thousands of tracks are available,
      reflecting data on a variety of tissues, cell types and cell lines from the human
      and mouse genomes. Users need to upload sets of selected and background regions.
      Results are displayed in customizable and easily interpretable figures.
      Availability and implementation: The R package and Shiny app are open source and
      available under the GPL v3 license. EpiAnnotator's web interface is accessible at
      http://computational-epigenomics.com/en/epiannotator. Contact:
      epiannotator@computational-epigenomics.com.

PMID- 29329371
TI  - Alcohol Use in Adolescence and Later Working Memory: Findings From a Large
      Population-Based Birth Cohort.
AB  - Aims: The study aimed to examine the association between adolescent alcohol use
      and working memory (WM) using a large population sample. Methods: Data from the
      Avon Longitudinal Study of Parents and Children were used to investigate the
      association between alcohol use at age 15 years and WM 3 years later, assessed
      using the N-back task (N ~ 3300). A three-category ordinal variable captured
      mutually exclusive alcohol groupings ranging in order of severity (i.e. low
      alcohol users, frequent drinkers and frequent/binge drinkers). Differential
      dropout was accounted for using multiple imputation and inverse probability
      weighting. Adjustment was made for potential confounders. Results: There was
      evidence of an association between frequent/binge drinking (compared to the low
      alcohol group) and poorer performance on the 3-back task after adjusting for
      sociodemographic confounding variables, WM at age 11 years, and experience of a
      head injury/unconsciousness before age 11 years (beta = -0.23, 95% CI = -0.37 to 
      0.09, P = 0.001). However, this association was attenuated (beta = -0.12, 95% CI
      = -0.27 to 0.03, P = 0.11) when further adjusted for baseline measures of weekly
      cigarette tobacco and cannabis use. Weaker associations were found for the less
      demanding 2-back task. We found no evidence to suggest frequent drinking was
      associated with performance on either task. Conclusions: We found weak evidence
      of an association between sustained heavy alcohol use in mid-adolescence and
      impaired WM 3 years later. Although we cannot fully rule out the possibility of
      reverse causation, several potential confounding variables were included to
      address the directionality of the relationship between WM and alcohol use
      problems.

PMID- 29329374
TI  - SimulaTE: simulating complex landscapes of transposable elements of populations.

PMID- 29329373
TI  - Co-existing Hepatitis C and Alcoholic Liver Disease: A Diminishing Indication for
      Liver Transplantation?
AB  - Aims: To provide an overview of published literature on the interaction of
      alcohol and hepatitis C virus (HCV) in the accelerated progression of liver
      disease to cirrhosis as relates to decision-making for the management of the
      liver transplant candidate and recipient. Methods: General PubMed search was
      employed along with expert input to identify the relevant articles on the topic.
      The authors also utilized both backward and forward citation review of the
      relevant articles and reviews to identify articles on identified topic. Results:
      In HCV cases, heavy alcohol use has been associated with more severe fibrosis,
      but even low rates of use may have deleterious effects. Patients with chronic
      hepatitis C and alcoholic liver disease can be cured of the HCV-theoretically
      positively impacting outcome and reducing the need for liver transplantation.
      Current antiviral therapy achieves virologic cure or sustained viral response
      (SVR) in over 90% of cases. Antiviral therapy is so effective that most liver
      transplant candidates or recipients can be cured of HCV either prior to or after
      transplantation. However, despite successful antiviral therapy, liver disease may
      progress after SVR due to the effects of ongoing alcohol use. Conclusion:
      Antiviral therapy in patients with HCV plus alcohol should improve pre- and post
      transplant outcomes, but providers must remain firm in limiting use of alcohol to
      avoid progression of liver disease post HCV cure. Short Summary: Abusive alcohol
      use and chronic hepatitis C virus (HCV) commonly co-exist and both need to be
      addressed in liver disease. With high rates of HCV cure with new therapies,
      attention needs to turn toward ongoing abusive alcohol patterns that may
      determinately impact liver health both before and after liver transplant.

PMID- 29329375
TI  - Heterogeneous Redistribution of Facial Subcategory Information Within and Outside
      the Face-Selective Domain in Primate Inferior Temporal Cortex.
AB  - The inferior temporal cortex (ITC) contains neurons selective to multiple levels
      of visual categories. However, the mechanisms by which these neurons collectively
      construct hierarchical category percepts remain unclear. By comparing decoding
      accuracy with simultaneously acquired electrocorticogram (ECoG), local field
      potentials (LFPs), and multi-unit activity in the macaque ITC, we show that low
      frequency LFPs/ECoG in the early evoked visual response phase contain sufficient
      coarse category (e.g., face) information, which is homogeneous and enhanced by
      spatial summation of up to several millimeters. Late-induced high-frequency LFPs
      additionally carry spike-coupled finer category (e.g., species, view, and
      identity of the face) information, which is heterogeneous and reduced by spatial
      summation. Face-encoding neural activity forms a cluster in similar cortical
      locations regardless of whether it is defined by early evoked low-frequency
      signals or late-induced high-gamma signals. By contrast, facial subcategory
      encoding activity is distributed, not confined to the face cluster, and
      dynamically increases its heterogeneity from the early evoked to late-induced
      phases. These findings support a view that, in contrast to the homogeneous and
      static coarse category-encoding neural cluster, finer category-encoding clusters
      are heterogeneously distributed even outside their parent category cluster and
      dynamically increase heterogeneity along with the local cortical processing in
      the ITC.

PMID- 29329377
TI  - Endometrial stem cell-derived granulocyte-colony stimulating factor attenuates
      endometrial fibrosis via sonic hedgehog transcriptional activator Gli2.
AB  - Intrauterine adhesion (IUA) is characterized by endometrial fibrosis, which
      ultimately leads to menstrual abnormalities, infertility, and recurrent
      miscarriages. The Shh/Gli2 pathway plays a critical role in tissue fibrogenesis
      and regeneration; Gli2 activation induces profibrogenic effects in various
      tissues, such as the liver and kidney. However, the role of Gli2 in endometrial
      fibrosis remains unknown. The purpose of this study was to test the hypothesis
      that activated Gli2 promotes endometrial fibrosis. Endometrial samples from
      moderate and severe IUA patients exhibited significantly enhanced expression of
      Gli2 compared with normal endometrial samples and mild IUA samples. Transfection
      with overactive Gli2 plasmids induced higher fibrosis-related protein expression,
      while blocking Gli2 signaling with cyclopamine caused the opposite effect in
      endometriotic stromal cells (ESCs), including inducing cell-cycle arrest.
      Menstrual-derived stem cell conditioned medium (MenSCs-CM) reduced endometrial
      fibrosis by reducing Gli2 protein levels and causing cell-cycle arrest in ESCs
      through granulocyte-colony stimulating factor (G-CSF). The effect was weakened
      after neutralization with a G-CSF antibody. Gli2 overexpression reduced the
      effects of MenSC-CM and G-CSF on fibrosis and cell-cycle progression in vitro.
      The antifibrotic effect of G-CSF was also observed in murine model. These
      findings demonstrate that Gli2 signaling promotes endometrial fibrosis, and the
      inhibition of Gli2 through MenSCs-secreted G-CSF may be of therapeutic value for
      managing endometrial fibrosis.

PMID- 29329376
TI  - Soil microbial species loss affects plant biomass and survival of an introduced
      bacterial strain, but not inducible plant defences.
AB  - Background and Aims: Plant growth-promoting rhizobacteria (PGPR) strains can
      influence plant-insect interactions. However, little is known about the effect of
      changes in the soil bacterial community in general and especially the loss of
      rare soil microbes on these interactions. Here, the influence of rare soil
      microbe reduction on induced systemic resistance (ISR) in a wild ecotype of
      Arabidopsis thaliana against the aphid Myzus persicae was investigated. Methods:
      To create a gradient of microbial abundances, soil was inoculated with a serial
      dilution of a microbial community and responses of Arabidopsis plants that
      originated from the same site as the soil microbes were tested. Plant biomass,
      transcription of genes involved in plant defences, and insect performance were
      measured. In addition, the effects of the PGPR strain Pseudomonas fluorescens
      SS101 on plant and insect performance were tested under the influence of the
      various soil dilution treatments. Key Results: Plant biomass showed a hump-shaped
      relationship with soil microbial community dilution, independent of aphid or
      Pseudomonas treatments. Both aphid infestation and inoculation with Pseudomonas
      reduced plant biomass, and led to downregulation of PR1 (salicylic acid
      responsive gene) and CYP79B3 (involved in synthesis of glucosinolates). Aphid
      performance and gene transcription were unaffected by soil dilution. Conclusions:
      Neither the loss of rare microbial species, as caused by soil dilution, nor
      Pseudomonas affect the resistance of A. thaliana against M. persicae. However,
      both Pseudomonas survival and plant biomass respond to rare species loss. Thus,
      loss of rare soil microbial species can have a significant impact on both above-
      and below-ground organisms.

PMID- 29329378
TI  - Historical crossroads in the conceptual delineation of apathy in Parkinson's
      disease.

PMID- 29329379
TI  - Asymptomatic Bacteriuria.

PMID- 29329381
TI  - The winding path towards rationale anti-thrombotic therapy to prevent stroke in
      patients with atrial fibrillation.

PMID- 29329380
TI  - Circulating microRNAs as potential biomarkers of disease activity and structural
      damage in ankylosing spondylitis patients.
AB  - Ankylosing spondylitis (AS) remains difficult to diagnose before irreversible
      damage to sacroiliac joint is noticeable. Circulating microRNAs have demonstrated
      to serve as diagnostic tools for several human diseases. Here, we analysed plasma
      microRNAs to identify potential AS biomarkers. Higher expression levels of
      microRNA (miR)-146a-5p, miR-125a-5p, miR-151a-3p and miR-22-3p, and lower
      expression of miR-150-5p, and miR-451a were found in AS versus healthy donors.
      Interestingly, higher miR-146a-5p, miR-125a-5p, miR-151a-3p, miR-22-3p and miR
      451a expression was also observed in AS than psoriatic arthritis patients. The
      areas under the curve, generated to assess the accuracy of microRNAs as
      diagnostic biomarkers for AS, ranged from 0.614 to 0.781; the six-microRNA
      signature reached 0.957. Bioinformatics analysis revealed that microRNAs targeted
      inflammatory and bone remodeling genes, underlying their potential role in this
      pathology. Indeed, additional studies revealed an association between these six
      microRNAs and potential target proteins related to AS pathophysiology.
      Furthermore, miR-146a-5p, miR-125a-5p and miR-22-3p expression was increased in
      active versus non-active patients. Moreover, miR-125a-5p, miR-151a-3p, miR-150-5p
      and miR-451a expression was related to the presence of syndesmophytes in AS
      patients. Overall, this study identified a six-plasma microRNA signature that
      could be attractive candidates as non-invasive biomarkers for the AS diagnosis,
      and may help to elucidate the disease pathogenesis.

PMID- 29329383
TI  - Reply to Johnson.

PMID- 29329382
TI  - Adolescent Synthetic Cannabinoid Exposure Produces Enduring Changes in Dopamine
      Neuron Activity in a Rodent Model of Schizophrenia Susceptibility.
AB  - Background: Epidemiological studies recognize cannabis intake as a risk factor
      for schizophrenia, yet the majority of adolescents who use marijuana do not
      develop psychosis. Similarly, the abuse of synthetic cannabinoids poses a risk
      for psychosis. For these reasons, it is imperative to understand the effects of
      adolescent cannabinoid exposure in susceptible individuals. Methods: We recently
      developed a novel rodent model of schizophrenia susceptibility, the F2
      methylazoxymethanol acetate rat, where only a proportion (~40%) of rats display a
      schizophrenia-like phenotype. Using this model, we examined the effects of
      adolescent synthetic cannabinoid exposure (0.2 mg/kg WIN55, 212-2, i.p.) or
      adolescent endocannabinoid upregulation (0.3 mg/kg URB597, i.p.) on dopamine
      neuron activity and amphetamine sensitivity in adulthood. Results: Adolescent
      synthetic cannabinoid exposure significantly increased the proportion of
      susceptible rats displaying a schizophrenia-like hyperdopaminergic phenotype
      after puberty without producing any observable alterations in control rats.
      Furthermore, this acquired phenotype appears to correspond with alterations in
      parvalbumin interneuron function within the hippocampus. Endocannabinoid
      upregulation during adolescence also increased the proportion of susceptible rats
      developing an increase in dopamine neuron activity; however, it did not alter the
      behavioral response to amphetamine, further emphasizing differences between
      exogenous and endogenous cannabinoids. Conclusions: Taken together, these studies
      provide experimental evidence that adolescent synthetic cannabinoid exposure may
      contribute to psychosis in susceptible individuals.

PMID- 29329384
TI  - Plaque erosion: a new in vivo diagnosis and a potential major shift in the
      management of patients with acute coronary syndromes.
AB  - Pathology and in vivo imaging studies have identified superficial plaque erosion
      as a frequent and important mechanism underlying acute coronary syndromes (ACS).
      In contrast with plaque rupture, the pathophysiological mechanisms leading to
      plaque erosion remain poorly understood. The advent of intravascular imaging
      techniques, particularly optical coherence tomography, has aided understanding of
      this mode of ACS in vivo by complementing previous insights from pathology
      studies. Appreciation of the distinct biological and clinical mechanisms of
      plaque erosion points to the possibility of tailored management strategies for
      patients presenting with ACS.

PMID- 29329385
TI  - Reassessing the Evidence for Capacity Limits in Neural Signals Related to Working
      Memory.
AB  - In 2004, two landmark studies described the discovery of brain imaging
      (functional magnetic resonance imaging and electroencephalography) signals that
      increase with the number of items held in visual working memory (WM). These
      studies claimed that the signals leveled off (plateaued) once the number of
      memoranda reached the capacity of WM, as estimated by the prevailing model of the
      time. However, alternative models were not considered, and changing concepts of
      WM in the more than a decade since these studies were published necessitate a re
      evaluation of their findings; newer models that provide the most accurate account
      of behavioral data do not incorporate a fixed limit on the number of items
      stored. Furthermore, an important claim made about the original studies, that
      signals plateau at each individual's estimated capacity, has never been tested.
      Here, we pit the plateau model of signal strength against an alternative,
      saturation model, a biophysically plausible account in which signals increase
      continuously without plateau. We show that the saturation model provides a better
      description of the original data, challenging the assumption that imaging results
      provide evidence for a fixed item limit in WM.

PMID- 29329386
TI  - The role of service readiness and health care facility factors in attrition from
      Option B+ in Haiti: a joint examination of electronic medical records and service
      provision assessment survey data.
AB  - Background: Option B+ is a strategy wherein pregnant or breastfeeding women with
      HIV are enrolled in lifelong antiretroviral therapy (ART) for prevention of
      mother-to-child transmission (PMTCT) of HIV. In Haiti, attrition from Option B+
      is problematic and variable across health care facilities. This study explores
      service readiness and other facility factors as predictors of Option B+ attrition
      in Haiti. Methods: This analysis used longitudinal data from 2012 to 2014 from
      the iSante electronic medical record system and cross-sectional data from Haiti's
      2013 Service Provision Assessment. Predictors included Service Availability and
      Readiness Assessment (SARA) measures for antenatal care (ANC), PMTCT, HIV care
      services and ART services; general facility characteristics and patient-level
      factors. Multivariable Cox proportional hazards models modelled the time to first
      attrition. Results: Analysis of data from 3147 women at 63 health care facilities
      showed no significant relationships between SARA measures and attrition. Having
      integrated ANC/PMTCT care and HIV-related training were significant protective
      factors. Being a public-sector facility, having a greater number of quality
      improvement activities and training in ANC were significant risk factors.
      Conclusion: Several facility-level factors were associated with Option B+
      attrition. Future research is needed to explore unmeasured facility factors,
      clarify causal relationships, and incorporate community-level factors into the
      analysis of Option B+ attrition.

PMID- 29329387
TI  - Patients with acephalic spermatozoa syndrome linked to SUN5 mutations have a
      favorable pregnancy outcome from ICSI.
AB  - STUDY QUESTION: Are Sad1 and UNC84 domain containing 5 (SUN5) mutations
      associated with the outcomes of ICSI in patients with acephalic spermatozoa
      syndrome (ASS)? SUMMARY ANSWER: Despite highly abnormal sperm morphology, ASS
      patients with SUN5 mutations have a favorable pregnancy outcome following ICSI.
      WHAT IS KNOWN ALREADY: ASS is a rare cause of infertility characterized by the
      production of a majority of headless spermatozoa, along with a small proportion
      of intact spermatozoa with an abnormal head-tail junction. Previous studies have
      demonstrated that SUN5 mutations may cause ASS. Several studies showed that ICSI
      could help patients with ASS father children. STUDY DESIGN, SIZE, DURATION: This
      retrospective cohort study included 11 infertile ASS males with SUN5 mutations.
      Five of them underwent five ICSI cycles. Their ICSI results were compared to men
      with ASS without SUN5 mutations (n = 3) and to men with multiple morphological
      abnormalities of the sperm flagella (MMAF) (n = 9). All ICSI treatments were
      completed between Jan 2011 and May 2017. PARTICIPANTS/MATERIALS, SETTING,
      METHODS: Sanger DNA sequencing was used to detect mutations in SUN5. Clinical and
      biological data were collected from patients at the fertility center. MAIN
      RESULTS AND THE ROLE OF CHANCE: Sanger sequencing validated 11 patients with SUN5
      mutations. Three novel mutations in SUN5 (c.829C>T [p.Q277*]; c.1067G>A
      [p.R356H]; c.211+1 insGT [p.S71Cfs11*]) were identified in three patients. The
      rates of fertilization, good-quality embryos and pregnancy for five patients with
      SUN5 mutations following ICSI were 81.5%, 81.8% and 100%, respectively. The rates
      of fertilization and good-quality embryos in patients with MMAF were
      significantly lower compared with ASS patients (65.6 versus 82.4%, P = 0.039 and
      53.6 versus 85.2%, P = 0.031, respectively). There were no differences in ICSI
      results between ASS patients with and without SUN5 mutations. LIMITATIONS,
      REASONS FOR CAUTION: Only a small number patients with SUN5 mutations was
      available because of its rare incidence. WIDER IMPLICATIONS OF THE FINDINGS:
      Patients with ASS can be effectively treated with ICSI. SUN5 mutations may be one
      of the genetic causes of ASS. STUDY FUNDING/COMPETING INTEREST(S): This study was
      supported by the National Natural Science Foundation of China (81401251,
      81370754, and 81170559), the Jiangsu Province Special Program of Medical Science
      (BL2012009, ZX201110, FXK201221) and a project funded by PAPD of the Priority
      Academic Program Development of Jiangsu High Education Institutions (JX10231802).
      None of the authors have any competing interests.

PMID- 29329388
TI  - A Series of Deaths Involving Carfentanil in the UK and Associated Post-mortem
      Blood Concentrations.
AB  - The potent opioid and veterinary drug, carfentanil has recently entered the
      illicit drug market, especially in relation to heroin and cocaine. Recent
      publications have reported carfentanil concentrations found in fatalities
      occurring in the USA. This article presents the toxicological findings in seven
      heroin/cocaine cases occurring in the UK within a short period of time where
      carfentanil was detected and measured. Carfentanil was detected along with other
      drugs in all cases with no alcohol detected in the post-mortem blood in any of
      the cases. Of the other drugs detected, of particular note, cannabinoids were
      detected in three, cocaine in four, other opioids (methadone, dihydrocodeine and
      tramadol) in four and benzodiazepines were detected in four of the seven
      fatalities. A high concentration of ketamine and norketamine was found in one
      case. Morphine and its glucuronide metabolites were also measured where detected
      in six of the seven cases. The carfentanil concentrations were found to be
      between 0.22 and 3.3 ng/mL (mean 0.93, median 0.66 ng/mL) in post-mortem femoral
      blood. In one case where aortic and ventricular post-mortem blood was submitted
      for analysis in addition to femoral blood, comparative concentrations of 1.05
      (aortic), 0.57 (ventricular) and 0.50 (femoral) ng/mL were found. The
      concentrations support the necessity to ensure laboratory detection methods for
      carfentanil and subsequent measurement are appropriate as concentrations below
      0.3 ng/mL may be present in post-mortem blood. The concentrations also support
      the notion that there is no particular "toxic" or "fatal" post-mortem blood
      carfentanil concentration associated with its use.

PMID- 29329389
TI  - In vivo daptomycin efficacy against experimental vancomycin-resistant
      Enterococcus faecium endocarditis.
AB  - Objectives: Daptomycin has become a first-line therapeutic option for vancomycin
      resistant Enterococcus faecium infective endocarditis (IE). Although high doses
      (>=8 mg/kg) are often recommended, optimal doses, particularly for strains with
      MICs close to the susceptibility breakpoint (4 mg/L), are still debated. Methods:
      Daptomycin efficacy at doses equivalent to 8 mg/kg daptomycin (DAP8) and 12 mg/kg
      daptomycin (DAP12) in humans was evaluated in a rabbit model of aortic valve IE
      induced by 108 cfu of E. faecium reference strain Aus0004 (daptomycin MIC = 2
      mg/L) or its in vitro mutant strain Mut4 (daptomycin MIC = 4 mg/L). Treatment
      began 48 h post-inoculation and lasted 5 days. Results: With Aus0004, the median
      log10 cfu/g of vegetations was significantly lower after DAP8 and DAP12 versus
      controls [6.05 (n = 12) and 2.15 (n = 10) versus 9.14 (n = 11), respectively; P <
      0.001], with DAP12 being more effective than DAP8 concerning vegetation bacterial
      load (P < 0.001) and percentages of sterile vegetations (100% versus 0%,
      respectively; P < 0.001). Daptomycin-resistant Aus0004 mutants were detected in
      8.3% of DAP8-treated vegetations. With Mut4, the median log10 cfu/g of
      vegetations was significantly lower after DAP8 and DAP12 versus controls [7.7 (n
      = 11) and 6.95 (n = 10) versus 9.59 (n = 11), respectively; P = 0.001 and P =
      0.002], without any between-dose difference, but no vegetation was sterile.
      Moreover, 7 of 11 (63.6%) and 7 of 9 (77.8%) vegetations contained resistant
      mutants after DAP8 and DAP12, respectively. Conclusions: DAP12 was the most
      successful strategy against IE due to a WT E. faecium strain (daptomycin MIC = 2
      mg/L). To treat IE strains with MIC = 4 mg/L, DAP8 or DAP12 monotherapy was
      poorly effective with the risk of resistant mutant emergence. Reassessment of the
      daptomycin susceptibility breakpoint for enterococci seems necessary.

PMID- 29329390
TI  - Human oocyte calcium analysis predicts the response to assisted oocyte activation
      in patients experiencing fertilization failure after ICSI.
AB  - STUDY QUESTION: Can human oocyte calcium analysis predict fertilization success
      after assisted oocyte activation (AOA) in patients experiencing fertilization
      failure after ICSI? SUMMARY ANSWER: ICSI-AOA restores the fertilization rate only
      in patients displaying abnormal Ca2+ oscillations during human oocyte activation.
      WHAT IS KNOWN ALREADY: Patients capable of activating mouse oocytes and who
      showed abnormal Ca2+ profiles after mouse oocyte Ca2+ analysis (M-OCA), have
      variable responses to ICSI-AOA. It remains unsettled whether human oocyte Ca2+
      analysis (H-OCA) would yield an improved accuracy to predict fertilization
      success after ICSI-AOA. STUDY DESIGN, SIZE, DURATION: Sperm activation potential
      was first evaluated by MOAT. Subsequently, Ca2+ oscillatory patterns were
      determined with sperm from patients showing moderate to normal activation
      potential based on the capacity of human sperm to generate Ca2+ responses upon
      microinjection in mouse and human oocytes. Altogether, this study includes a
      total of 255 mouse and 122 human oocytes. M-OCA was performed with 16 different
      sperm samples before undergoing ICSI-AOA treatment. H-OCA was performed for 11
      patients who finally underwent ICSI-AOA treatment. The diagnostic accuracy to
      predict fertilization success was calculated based on the response to ICSI-AOA.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients experiencing low or total
      failed fertilization after conventional ICSI were included in the study. All
      participants showed moderate to high rates of activation after MOAT. Metaphase II
      (MII) oocytes from B6D2F1 mice were used for M-OCA. Control fertile sperm samples
      were used to obtain a reference Ca2+ oscillation profile elicited in human
      oocytes. Donated human oocytes, non-suitable for IVF treatments, were collected
      and vitrified at MII stage for further analysis by H-OCA. MAIN RESULTS AND THE
      ROLE OF CHANCE: M-OCA and H-OCA predicted the response to ICSI-AOA in 8 out of 11
      (73%) patients. Compared to M-OCA, H-OCA detected the presence of sperm
      activation deficiencies with greater sensitivity (75 vs 100%, respectively). ICSI
      AOA never showed benefit to overcome fertilization failure in patients showing
      normal capacity to generate Ca2+ oscillations in H-OCA and was likely to be
      beneficial in cases displaying abnormal H-OCA Ca2+ oscillations patterns.
      LIMITATIONS, REASONS FOR CAUTION: The scarce availability of human oocytes
      donated for research purposes is a limiting factor to perform H-OCA. Ca2+ imaging
      requires specific equipment to monitor fluorescence changes over time. WIDER
      IMPLICATIONS OF THE FINDINGS: H-OCA is a sensitive test to diagnose gamete-linked
      fertilization failure. H-OCA allows treatment counseling for couples experiencing
      ICSI failures to either undergo ICSI-AOA or to participate in gamete donation
      programs. The present data provide an important template of the Ca2+ signature
      observed during human fertilization in cases with normal, low and failed
      fertilization after conventional ICSI. STUDY FUNDING/COMPETING INTEREST(S): This
      work was supported by the Flemish fund for scientific research (FWO-Vlaanderen,
      G060615N). The authors have no conflict of interest to declare.

PMID- 29329391
TI  - Oxidative burst and Dectin-1-triggered phagocytosis affected by norepinephrine
      and endocannabinoids: implications for fungal clearance under stress.
AB  - A prolonged stress burden is known to hamper the efficiency of both the innate
      and the adaptive immune systems and to attenuate the stress responses by the
      catecholaminergic and endocannabinoid (EC) systems. Key mechanisms of innate
      immunity are the eradication of pathogens through phagocytosis and the
      respiratory burst. We tested the concentration-dependent, spontaneous and
      stimulated (via TNFalpha and N-formylmethionine-leucyl-phenylalanine) release of
      reactive oxygen species (ROS) by human polymorphonuclear leukocytes (PMNs) in
      vitro in response to norepinephrine (NE) and AM1241, a pharmacological ligand for
      the EC receptor CB2. We evaluated phagocytosis of Dectin-1 ligating zymosan
      particles and tested the cytokine response against Candida antigen in an in vitro
      cytokine release assay. Increasing concentrations of NE did not affect
      phagocytosis, yet stimulated ROS release was attenuated gradually reaching
      maximum suppression at 500 nM. Adrenergic receptor (AR) mechanisms using non-AR
      selective (labetalol) as well as specific alpha-(prazosin) and beta-(propranolol)
      receptor antagonists were tested. Results show that only labetalol and
      propranolol were able to recuperate cytotoxicity in the presence of NE,
      evidencing a beta-receptor-mediated effect. The CB2 agonist, AM1241, inhibited
      phagocytosis at 10 uM and spontaneous peroxide release by PMNs. Use of the
      inverse CB2 receptor agonist SR144528 led to partial recuperation of ROS
      production, confirming the functional role of CB2. Additionally, AM1241 delayed
      early activation of monocytes and induced suppression of IL-2 and IL-6 levels in
      response to Candida via lower activity of mammalian target of rapamycin (mTOR).
      These findings provide new insights into key mechanisms of innate immunity under
      stressful conditions where ligands to the sympatho-adrenergic and EC system are
      released.

PMID- 29329393
TI  - TGF-beta-mediated NADPH oxidase 4-dependent oxidative stress promotes colistin
      induced acute kidney injury.
AB  - Background: Colistin (polymyxin E) is an important constituent of the polymyxin
      class of cationic polypeptide antibiotics. Intrarenal oxidative stress can
      contribute to colistin-induced nephrotoxicity. Nicotinamide adenine dinucleotide
      3-phosphate oxidases (Noxs) are important sources of reactive oxygen species.
      Among the various types of Noxs, Nox4 is predominantly expressed in the kidney.
      Objectives: We investigated the role of Nox4 and benefit of Nox4 inhibition in
      colistin-induced acute kidney injury using in vivo and in vitro models. Methods:
      Human proximal tubular epithelial (HK-2) cells were treated with colistin with or
      without NOX4 knockdown, or GKT137831 (most specific Nox1/4 inhibitor). Effects of
      Nox4 inhibition on colistin-induced acute kidney injury model in Sprague-Dawley
      rats were examined. Results: Nox4 expression in HK-2 cells significantly
      increased following colistin exposure. SB4315432 (transforming growth factor
      beta1 receptor I inhibitor) significantly inhibited Nox4 expression in HK-2
      cells. Knockdown of NOX4 transcription reduced reactive oxygen species
      production, lowered the levels of pro-inflammatory markers (notably mitogen
      activated protein kinases) implicated in colistin-induced nephrotoxicity and
      attenuated apoptosis by altering Bax and caspase 3/7 activity. Pretreatment with
      GKT137831 replicated these effects mediated by downregulation of mitogen
      activated protein kinase activities. In a rat colistin-induced acute kidney
      injury model, administration of GKT137831 resulted in attenuated colistin-induced
      acute kidney injury as indicated by attenuated impairment of glomerulus function,
      preserved renal structures, reduced expression of 8-hydroxyguanosine and fewer
      apoptotic cells. Conclusions: Collectively, these findings identify Nox4 as a key
      source of reactive oxygen species responsible for kidney injury in colistin
      induced nephrotoxicity and highlight a novel potential way to treat drug-related
      nephrotoxicity.

PMID- 29329392
TI  - Risk of pancreatic cancer associated with family history of cancer and other
      medical conditions by accounting for smoking among relatives.
AB  - Background: Family history (FH) of pancreatic cancer (PC) has been associated
      with an increased risk of PC, but little is known regarding the role of
      inherited/environmental factors or that of FH of other comorbidities in PC risk.
      We aimed to address these issues using multiple methodological approaches.
      Methods: Case-control study including 1431 PC cases and 1090 controls and a
      reconstructed-cohort study (N = 16 747) made up of their first-degree relatives
      (FDR). Logistic regression was used to evaluate PC risk associated with FH of
      cancer, diabetes, allergies, asthma, cystic fibrosis and chronic pancreatitis by
      relative type and number of affected relatives, by smoking status and other
      potential effect modifiers, and by tumour stage and location. Familial
      aggregation of cancer was assessed within the cohort using Cox proportional
      hazard regression. Results: FH of PC was associated with an increased PC risk
      [odds ratio (OR) = 2.68; 95% confidence interval (CI): 2.27-4.06] when compared
      with cancer-free FH, the risk being greater when >= 2 FDRs suffered PC (OR =
      3.88; 95% CI: 2.96-9.73) and among current smokers (OR = 3.16; 95% CI: 2.56-5.78,
      interaction FHPC*smoking P-value = 0.04). PC cumulative risk by age 75 was 2.2%
      among FDRs of cases and 0.7% in those of controls [hazard ratio (HR) = 2.42; 95%
      CI: 2.16-2.71]. PC risk was significantly associated with FH of cancer (OR =
      1.30; 95% CI: 1.13-1.54) and diabetes (OR = 1.24; 95% CI: 1.01-1.52), but not
      with FH of other diseases. Conclusions: The concordant findings using both
      approaches strengthen the notion that FH of cancer, PC or diabetes confers a
      higher PC risk. Smoking notably increases PC risk associated with FH of PC.
      Further evaluation of these associations should be undertaken to guide PC
      prevention strategies.

PMID- 29329395
TI  - Open-Access Physical Activity Programs for Older Adults: A Pragmatic and
      Systematic Review.
AB  - Background and Objectives: Open-access, community-based programs are recommended
      to assist older adults in meeting physical activity guidelines, but the
      characteristics, impact, and scalability of these programs is less understood.
      The Land-Grant University Cooperative Extension System, an organization providing
      education through county-based educators, functions as a delivery system for
      these programs. A systematic review was conducted to determine characteristics of
      effective older adult physical activity programs and the extent to which programs
      delivered in Extension employ these characteristics. Research Design and Methods:
      A systematic review of peer-reviewed and grey literature was conducted from
      August 2016 to February 2017. The review was limited to open-access (available to
      all), community-based physical activity interventions for older adults (>=65
      years of age). The peer-reviewed literature search was conducted in PubMed and
      EBSCOhost; the grey literature search for Extension interventions was conducted
      through Extension websites, Land-Grant Impacts, and the Journal of Extension.
      Results: Sixteen peer-reviewed studies and 17 grey literature sources met
      inclusion criteria and were analyzed. Peer-reviewed and Extension programs were
      similar in their limited use of behavioral theories and group-based strategies.
      Compared to Extension programs, those in the peer-reviewed literature were more
      likely to use a combination of physical activity components and be delivered by
      trained professionals. Discussion and Implications: The results indicate notable
      differences between peer-reviewed literature and Extension programs and present
      an opportunity for Extension programs to more effectively use evidence-based
      program characteristics, including behavioral theories and group dynamics, a
      combination of physical activity components, and educator/agent-trained delivery
      agents.

PMID- 29329394
TI  - Analysis of the Aedes albopictus C6/36 genome provides insight into cell line
      utility for viral propagation.
AB  - Background: The 50-year-old Aedes albopictus C6/36 cell line is a resource for
      the detection, amplification, and analysis of mosquito-borne viruses including
      Zika, dengue, and chikungunya. The cell line is derived from an unknown number of
      larvae from an unspecified strain of Aedes albopictus mosquitoes. Toward improved
      utility of the cell line for research in virus transmission, we present an
      annotated assembly of the C6/36 genome. Results: The C6/36 genome assembly has
      the largest contig N50 (3.3 Mbp) of any mosquito assembly, presents the sequences
      of both haplotypes for most of the diploid genome, reveals independent null
      mutations in both alleles of the Dicer locus, and indicates a male-specific
      genome. Gene annotation was computed with publicly available mosquito transcript
      sequences. Gene expression data from cell line RNA sequence identified enrichment
      of growth-related pathways and conspicuous deficiency in aquaporins and inward
      rectifier K+ channels. As a test of utility, RNA sequence data from Zika-infected
      cells were mapped to the C6/36 genome and transcriptome assemblies. Host
      subtraction reduced the data set by 89%, enabling faster characterization of
      nonhost reads. Conclusions: The C6/36 genome sequence and annotation should
      enable additional uses of the cell line to study arbovirus vector interactions
      and interventions aimed at restricting the spread of human disease.

PMID- 29329396
TI  - Patient-level benefits associated with decentralization of antiretroviral therapy
      services to primary health facilities in Malawi and Uganda.
AB  - Background: The Lablite project captured information on access to antiretroviral
      therapy (ART) at larger health facilities ('hubs') and lower-level health
      facilities ('spokes') in Phalombe district, Malawi and in Kalungu district,
      Uganda. Methods: We conducted a cross-sectional survey among patients who had
      transferred to a spoke after treatment initiation (Malawi, n=54; Uganda, n=33),
      patients who initiated treatment at a spoke (Malawi, n=50; Uganda, n=44) and
      patients receiving treatment at a hub (Malawi, n=44; Uganda, n=46). Results: In
      Malawi, 47% of patients mapped to the two lowest wealth quintiles (Q1-Q2);
      patients at spokes were poorer than at a hub (57% vs 23% in Q1-Q2; p<0.001). In
      Uganda, 7% of patients mapped to Q1-Q2; patients at the rural spoke were poorer
      than at the two peri-urban facilities (15% vs 4% in Q1-Q2; p<0.001). The median
      travel time one way to a current ART facility was 60 min (IQR 30-120) in Malawi
      and 30 min (IQR 20-60) in Uganda. Patients who had transferred to the spokes
      reported a median reduction in travel time of 90 min in Malawi and 30 min in
      Uganda, with reductions in distance and food costs. Conclusions: Decentralizing
      ART improves access to treatment. Community-level access to treatment should be
      considered to further minimize costs and time.

PMID- 29329397
TI  - MINAR1 is a Notch2-binding protein that inhibits angiogenesis and breast cancer
      growth.
AB  - Intrinsically disordered proteins (IDPs)/intrinsically unstructured proteins are
      characterized by the lack of fixed or stable tertiary structure, and are
      increasingly recognized as an important class of proteins with major roles in
      signal transduction and transcriptional regulation. In this study, we report the
      identification and functional characterization of a previously uncharacterized
      protein (UPF0258/KIAA1024), major intrinsically disordered Notch2-associated
      receptor 1 (MINAR1). While MINAR1 carries a single transmembrane domain and a
      short cytoplasmic domain, it has a large extracellular domain that shares no
      similarity with known protein sequences. Uncharacteristically, MINAR1 is a highly
      IDP with nearly 70% of its amino acids sequences unstructured. We demonstrate
      that MINAR1 physically interacts with Notch2 and its binding to Notch2 increases
      its stability and function. MINAR1 is widely expressed in various tissues
      including the epithelial cells of the breast and endothelial cells of blood
      vessels. MINAR1 plays a negative role in angiogenesis as it inhibits angiogenesis
      in cell culture and in mouse matrigel plug and zebrafish angiogenesis models.
      Furthermore, while MINAR1 is highly expressed in the normal human breast, its
      expression is significantly downregulated in advanced human breast cancer and its
      re-expression in breast cancer cells inhibited tumor growth. Our study
      demonstrates that MINAR1 is an IDP that negatively regulates angiogenesis and
      growth of breast cancer cells.

PMID- 29329398
TI  - LeNup: learning nucleosome positioning from DNA sequences with improved
      convolutional neural networks.
AB  - Motivation: Nucleosome positioning plays significant roles in proper genome
      packing and its accessibility to execute transcription regulation. Despite a
      multitude of nucleosome positioning resources available on line including
      experimental datasets of genome-wide nucleosome occupancy profiles and
      computational tools to the analysis on these data, the complex language of
      eukaryotic Nucleosome positioning remains incompletely understood. Results: Here,
      we address this challenge using an approach based on a state-of-the-art machine
      learning method. We present a novel convolutional neural network (CNN) to
      understand nucleosome positioning. We combined Inception-like networks with a
      gating mechanism for the response of multiple patterns and long term association
      in DNA sequences. We developed the open-source package LeNup based on the CNN to
      predict nucleosome positioning in Homo sapiens, Caenorhabditis elegans,
      Drosophila melanogaster as well as Saccharomyces cerevisiae genomes. We trained
      LeNup on four benchmark datasets. LeNup achieved greater predictive accuracy than
      previously published methods. Availability and implementation: LeNup is freely
      available as Python and Lua script source code under a BSD style license from
      https://github.com/biomedBit/LeNup. Contact: jhzhang@bit.edu.cn. Supplementary
      information: Supplementary data are available at Bioinformatics online.

PMID- 29329399
TI  - Yield Losses in Transgenic Cry1Ab and Non-Bt Corn as Assessed Using a Crop-Life
      Table Approach.
AB  - In this study, we constructed crop life tables for Bacillus thuringiensis
      Berliner (Bt) Cry1Ab and non-Bt corn hybrids, in which yield-loss factors and
      abundance of predaceous arthropods were recorded during 2 yr at two locations.
      Corn kernel/grain was the yield component that had the heaviest losses and that
      determined the overall yield loss in the corn hybrids across years and locations.
      Yield losses in both corn hybrids were primarily caused by kernel-destroying
      insects. Helicoverpa zea (Boddie) and Spodoptera frugiperda (Smith) (Lepidoptera:
      Noctuidae) were the key loss factors at one location, while at the other, the key
      loss factor was the silk fly larvae, Euxesta spp. (Diptera: Ulidiidae). Although
      the realized yield of corn grains was not different (P > 0.05) between Cry1Ab and
      non-Bt corn hybrids, the Bt corn hybrid reduced (P < 0.05) the damage by H. zea
      and S. frugiperda in three of the four field trials, particularly at the location
      where Lepidoptera were the key loss factors. As expected, no reduction in the
      abundance of predaceous arthropods was observed in Cry1Ab corn fields. Various
      species of natural enemies were recorded, particularly the earwig Doru luteipes
      (Scudder) (Dermaptera: Forficulidae), which was the most abundant and frequent
      predaceous insect. These results indicate that integration of pest management
      practices should be pursued to effectively minimize losses by kernel-destroying
      insects during corn reproductive stages when growing non-Bt or certain low-dose
      Bt corn cultivars for fall armyworm and corn earworm, such as those producing
      Cry1Ab or other Cry toxins.

PMID- 29329400
TI  - The decision to work after state pension age and how it affects quality of life:
      evidence from a 6-year English panel study.
AB  - Background: despite an increasing proportion of older people working beyond State
      Pension Age (SPA), little is known about neither the motivations for this
      decision nor whether, and to what extent, working beyond SPA affects quality of
      life (QoL). Methods: QoL was measured using the CASP-19 scale. Respondents in
      paid work beyond SPA were distinguished based on whether they reported financial
      constraints as the main reason for continuing in work. Linear regression models
      were used to assess the associations between paid work beyond SPA and CASP-19
      scores among men aged 65-74 and women aged 60-69 (n = 2,502) cross-sectionally
      and over time using Wave 4 and Wave 7 of the English Longitudinal Study of
      Ageing. Results: approximately, one in five respondents were in paid work beyond
      SPA, one-third of whom reported financial issues as the main reason. These
      individuals reported significantly lower CASP-19 scores (beta = -1.21) compared
      with those who retired at the expected/usual age. Respondents who declared being
      in paid work beyond SPA because they enjoyed their work or wanted to remain
      active, reported significantly higher QoL (beta = 1.62). Longitudinal analyses
      suggest that those who were working post-SPA by choice, but who had stopped
      working at follow-up, also reported marginally (P < 0.10) higher CASP-19 scores.
      Conclusions: potential QoL benefits of working beyond SPA need to be considered
      in light of individual motivations for extending working life. Given the trend
      towards working longer and the abolishment of mandatory retirement ages, it is
      important that older people maintain control over their decision to work in later
      life.

PMID- 29329402
TI  - Discovering foodborne illness in online restaurant reviews.
AB  - Objective: We developed a system for the discovery of foodborne illness mentioned
      in online Yelp restaurant reviews using text classification. The system is used
      by the New York City Department of Health and Mental Hygiene (DOHMH) to monitor
      Yelp for foodborne illness complaints. Materials and Methods: We built
      classifiers for 2 tasks: (1) determining if a review indicated a person
      experiencing foodborne illness and (2) determining if a review indicated multiple
      people experiencing foodborne illness. We first developed a prototype classifier
      in 2012 for both tasks using a small labeled dataset. Over years of system
      deployment, DOHMH epidemiologists labeled 13 526 reviews selected by this
      classifier. We used these biased data and a sample of complementary reviews in a
      principled bias-adjusted training scheme to develop significantly improved
      classifiers. Finally, we performed an error analysis of the best resulting
      classifiers. Results: We found that logistic regression trained with bias
      adjusted augmented data performed best for both classification tasks, with F1
      scores of 87% and 66% for tasks 1 and 2, respectively. Discussion: Our error
      analysis revealed that the inability of our models to account for long phrases
      caused the most errors. Our bias-adjusted training scheme illustrates how to
      improve a classification system iteratively by exploiting available biased
      labeled data. Conclusions: Our system has been instrumental in the identification
      of 10 outbreaks and 8523 complaints of foodborne illness associated with New York
      City restaurants since July 2012. Our evaluation has identified strong
      classifiers for both tasks, whose deployment will allow DOHMH epidemiologists to
      more effectively monitor Yelp for foodborne illness investigations.

PMID- 29329403
TI  - Host-Tree Selection by the Invasive Argentine Ant (Hymenoptera: Formicidae) in
      Relation to Honeydew-Producing Insects.
AB  - The Argentine ant, Linepithema humile (Mayr; Hymenoptera: Formicidae), is one of
      the world's most hazardous invasive species, and thus its eradication from Japan
      is important. Physical and chemical controls can be expensive and cause strong
      adverse effects on local terrestrial ecosystems regardless of their high
      efficacy. Here, presence/absence of host-tree selection by Argentine ants was
      investigated to understand the ant-honeydew-producing insects interactions in
      order to develop new cultural controls compatible with biodiversity conservation.
      Abundance of Argentine ants and their tree utilization ratio was measured among
      dominant roadside trees (Cinnamomum camphora, Myrica rubra, Nerium indicum,
      Rhaphiolepis indica var. umbellata, Juniperus chinensis var. kaizuka) in two
      areas around Kobe, Japan. Almost all ants collected were Argentine ants
      suggesting that native ants would have been competitively excluded. Tree
      utilization of Argentine ants clearly differed among host trees. Abundance of
      both Argentine ants and honeydew-producing insects and tree utilization rate of
      the ants were significantly lower in especially C. camphora and J. chinensis. Few
      Argentine ants were observed trailing on C. camphora, J. Chinensis, and N.
      indicum, most probably due to low abundance of honeydew-producing insects on
      these trees with the toxic and repellent chemical components. On the other hand,
      high abundance of both Argentine ants and homopterans were found in M. rubra and
      especially R. indica. We suggest that reductions of R. indica and M. rubra would
      lead to a decrease in abundance of honeydew-producing insects, and thus
      effectively control populations of Argentine ants. At the same time, planting of
      C. camphora, J. Chinensis, and N. indicum may also play a role in restraint
      efficacy against invasion of the invasive ants.

PMID- 29329404
TI  - Response.

PMID- 29329401
TI  - Morphological and Functional Characterization of Non-fast-Spiking GABAergic
      Interneurons in Layer 4 Microcircuitry of Rat Barrel Cortex.
AB  - GABAergic interneurons are notorious for their heterogeneity, despite
      constituting a small fraction of the neuronal population in the neocortex.
      Classification of interneurons is crucial for understanding their widespread
      cortical functions as they provide a complex and dynamic network, balancing
      excitation and inhibition. Here, we investigated different types of non-fast
      spiking (nFS) interneurons in Layer 4 (L4) of rat barrel cortex using whole-cell
      patch-clamp recordings with biocytin-filling. Based on a quantitative analysis on
      a combination of morphological and electrophysiological parameters, we identified
      5 distinct types of L4 nFS interneurons: 1) trans-columnar projecting
      interneurons, 2) locally projecting non-Martinotti-like interneurons, 3) supra
      granular projecting Martinotti-like interneurons, 4) intra-columnar projecting
      VIP-like interneurons, and 5) locally projecting neurogliaform-like interneurons.
      Trans-columnar projecting interneurons are one of the most striking interneuron
      types, which have not been described so far in Layer 4. They feature extensive
      axonal collateralization not only in their home barrel but also in adjacent
      barrels. Furthermore, we identified that most of the L4 nFS interneurons express
      somatostatin, while few are positive for the transcription factor Prox1. The
      morphological and electrophysiological characterization of different L4 nFS
      interneuron types presented here provides insights into their synaptic
      connectivity and functional role in cortical information processing.

PMID- 29329405
TI  - Solanaceous exocyst subunits are involved in immunity to diverse plant pathogens.
AB  - The exocyst, a multiprotein complex consisting of eight subunits, plays an
      essential role in many biological processes by mediating secretion of post-Golgi
      derived vesicles towards the plasma membrane. In recent years, roles for plant
      exocyst subunits in pathogen defence have been uncovered, largely based on
      studies in the model plant Arabidopsis. Only a few studies have been undertaken
      to assign the role of exocyst subunits in plant defence in other plants species,
      including crops. In this study, predicted protein sequences from exocyst subunits
      were retrieved by mining databases from the Solanaceous plants Nicotiana
      benthamiana, tomato, and potato. Subsequently, their evolutionary relationship
      with Arabidopsis exocyst subunits was analysed. Gene silencing in N. benthamiana
      showed that several exocyst subunits are required for proper plant defence
      against the (hemi-)biotrophic plant pathogens Phytophthora infestans and
      Pseudomonas syringae. In contrast, some exocyst subunits seem to act as
      susceptibility factors for the necrotrophic pathogen Botrytis cinerea.
      Furthermore, the majority of the exocyst subunits were found to be involved in
      callose deposition, suggesting that they play a role in basal plant defence. This
      study provides insight into the evolution of exocyst subunits in Solanaceous
      plants and is the first to show their role in immunity against multiple unrelated
      pathogens.

PMID- 29329406
TI  - Judgement of Breath Alcohol Concentration Levels Among Pedestrians in the Night
      Time Economy-A Street-Intercept Field Study.
AB  - Aims: To evaluate how well people in the night-time economy can assess their own
      breath alcohol concentration (BrAC), in the context of a change in breath alcohol
      limits for driving. Methods: We conducted a field study of 242 participants over
      5 nights in the central business district of a university town in New Zealand.
      Participants completed a short survey, which included questions on their self
      reported level of intoxication and the self-estimated BrAC. At the conclusion of
      the interview each participant was breath-tested. We compared actual and self
      estimated BrAC using a scatter plot and multiple regression methods. Results: The
      average BrAC error was 61.7 MUg/l, meaning that on average participants
      overestimate their BrAC. Participants with a BrAC below 487 MUg/l tended to
      overestimate their BrAC on average, and those with a BrAC above 487 MUg/l tended
      to underestimate their BrAC on average. Regression results supported this
      observation, but also found that men who are not 'out on a typical night'
      overestimate their BrAC by more. Conclusions: Drinkers in this naturalistic
      setting have little idea of their level of intoxication, as measured by BrAC.
      However, this uncertainty may be advantageous to public health outcomes, since if
      drinkers are uncertain about their level of intoxication relative to the legal
      limit, this may lead them to avoid drunk driving. Short Summary: A field study of
      drinkers in the night-time economy of a New Zealand university town was conducted
      to evaluate how well drinkers can assess their breath alcohol concentration
      (BrAC). Drinkers in this setting inaccurately estimate their intoxication, and
      those with higher BrAC tended to underestimate their BrAC on average.

PMID- 29329407
TI  - Transplant Buccaneers: P.K. Sen and India's First Heart Transplant, February
      1968.
AB  - On 17 February 1968, Bombay surgeon Prafulla Kumar Sen transplanted a human
      heart, becoming the fourth surgeon in the world to attempt the feat. Even though
      the patient survived just three hours, the feat won Sen worldwide acclaim. The
      ability of Sen's team to join the ranks of the world's surgical pioneers raises
      interesting questions. How was Sen able to transplant so quickly? He had to train
      a team of collaborators, import or reverse engineer technologies and techniques
      that had been developed largely in the United States, and begin conversations
      with Indian political authorities about the contested concept of brain death. The
      effort that this required raises questions of why. Sen, who worked at a city
      hospital in Bombay that could not provide basic care for all its citizens, sought
      a technology that epitomized high-risk high-cost, health care. To accomplish his
      feat, Sen navigated Cold War tensions and opportunities, situating his interests
      into those of his hospital, municipal authorities, Indian nationalism, Soviet and
      American authorities, the Rockefeller Foundation, and others. The many contexts
      and interests that made Sen's work possible created opportunities for many
      different judgments about the success or failure of medical innovation.

PMID- 29329408
TI  - An Orientation Map for Disparity-Defined Edges in Area V4.
AB  - Binocular disparity information is an important source of 3D perception. Neurons
      sensitive to binocular disparity are found in almost all major visual areas in
      nonhuman primates. In area V4, disparity processes are suggested for the purposes
      of 3D-shape representation and fine disparity perception. However, whether
      neurons in V4 are sensitive to disparity-defined edges used in shape
      representation is not clear. Additionally, a functional organization for
      disparity edges has not been demonstrated so far. With intrinsic signal optical
      imaging, we studied functional organization for disparity edges in the monkey
      visual areas V1, V2, and V4. We found that there is an orientation map in V4
      activated by edges purely defined by binocular disparity. This map is consistent
      with the orientation map obtained with regular luminance-defined edges,
      indicating a cue-invariant edge representation in this area. In contrast, such a
      map is much weaker in V2 and totally absent in V1. These findings reveal a
      hierarchical processing of 3D shape along the ventral pathway and the important
      role that V4 plays in shape-from-disparity detection.

PMID- 29329409
TI  - Recent development of Ori-Finder system and DoriC database for microbial
      replication origins.
AB  - DNA replication begins at replication origins in all three domains of life.
      Identification and characterization of replication origins are important not only
      in providing insights into the structure and function of the replication origins
      but also in understanding the regulatory mechanisms of the initiation step in DNA
      replication. The Z-curve method has been used in the identification of
      replication origins in archaeal genomes successfully since 2002. Furthermore, the
      Web servers of Ori-Finder and Ori-Finder 2 have been developed to predict
      replication origins in both bacterial and archaeal genomes based on the Z-curve
      method, and the replication origins with manual curation have been collected into
      an online database, DoriC. Ori-Finder system and DoriC database are currently
      used in the research field of DNA replication origins in prokaryotes, including:
      (i) identification of oriC regions in bacterial and archaeal genomes; (ii)
      discovery and analysis of the conserved sequences within oriC regions; and (iii)
      strand-biased analysis of bacterial genomes.Up to now, more and more predicted
      results by Ori-Finder system were supported by subsequent experiments, and Ori
      Finder system has been used to identify the replication origins in > 100 newly
      sequenced prokaryotes in their genome reports. In addition, the data in DoriC
      database have been widely used in the large-scale analyses of replication origins
      and strand bias in prokaryotic genomes. Here, we review the development of Ori
      Finder system and DoriC database as well as their applications. Some future
      directions and aspects for extending the application of Ori-Finder and DoriC are
      also presented.

PMID- 29329411
TI  - RE: Long-term Safety of Pregnancy Following Breast Cancer According to Estrogen
      Receptor Status.

PMID- 29329410
TI  - 1918 H1N1 Influenza Virus Replicates and Induces Proinflammatory Cytokine
      Responses in Extrarespiratory Tissues of Ferrets.
AB  - Background: The 1918 Spanish H1N1 influenza pandemic was the most severe recorded
      influenza pandemic with an estimated 20-50 million deaths worldwide. Even though
      it is known that influenza viruses can cause extrarespiratory tract complications
      which are often severe or even fatal-the potential contribution of
      extrarespiratory tissues to the pathogenesis of 1918 H1N1 virus infection has not
      been studied comprehensively. Methods: Here, we performed a time-course study in
      ferrets inoculated intranasally with 1918 H1N1 influenza virus, with special
      emphasis on the involvement of extrarespiratory tissues. Respiratory and
      extrarespiratory tissues were collected after inoculation for virological,
      histological, and immunological analysis. Results: Infectious virus was detected
      at high titers in respiratory tissues and, at lower titers in most
      extrarespiratory tissues. Evidence for active virus replication, as indicated by
      the detection of nucleoprotein by immunohistochemistry, was observed in the
      respiratory tract, peripheral and central nervous system, and liver.
      Proinflammatory cytokines were up-regulated in respiratory tissues, olfactory
      bulb, spinal cord, liver, heart, and pancreas. Conclusions: 1918 H1N1 virus
      spread to and induced cytokine responses in tissues outside the respiratory
      tract, which likely contributed to the severity of infection. Moreover, our data
      support the suggested link between 1918 H1N1 infection and central nervous system
      disease.

PMID- 29329413
TI  - Mapping a Filoviral Serologic Footprint in the Democratic Republic of the Congo:
      Who Goes There?

PMID- 29329412
TI  - Lhx8 ablation leads to massive autophagy of mouse oocytes associated with DNA
      damage.
AB  - Following proliferation of oogonia in mammals, great numbers of germ cells are
      discarded, primarily by apoptosis, while the remainder form primordial follicles
      (the ovarian reserve) that determine fertility and reproductive lifespan. More
      massive, rapid, and essentially total loss of oocytes, however, occurs when the
      transcription factor Lhx8 is ablated-though the cause and mechanism of germ cell
      loss from the Lhx8-/- ovaries has been unknown. We found that Lhx8-/- ovaries
      maintain the same number of germ cells throughout embryonic development; rapid
      decrease in the pool of oocytes starts shortly before birth. The loss results
      from activation of autophagy, which becomes overwhelming within the first
      postnatal week, with extracellular matrix proteins filling the space previously
      occupied by follicles to produce a fibrotic ovary. Associated with this process,
      as early as a few days before birth, Lhx8-/- oocytes failed to repair DNA damage
      which normally occurs when meiosis is initiated during embryonic development; and
      DNA damage repair genes were downregulated throughout the oocyte short lifespan.
      Based on gene expression analyses and morphological changes, we propose a model
      in which lineage-restricted failure of DNA repair triggers germ cell autophagy,
      causing premature depletion of the ovarian reserve in Lhx8-/- mice.

PMID- 29329414
TI  - Is big bad or bearable? Long-term renal transplant outcomes in obese recipients.
AB  - Background: The global obesity epidemic has implications for kidney
      transplantation. There are conflicting reports regarding the impact of obesity on
      long-term post-transplant outcomes. Aim: To explore the impact of body mass index
      (BMI) on long-term outcomes after kidney transplantation. Design: The association
      between BMI and cardiovascular disease, cancer, post-transplant diabetes
      mellitus, graft and recipient survival was investigated in recipients who had
      been transplanted at least ten years previously. Methods: All consecutive adult
      renal transplant recipients who received first, deceased donor, transplants
      between 1986 and 2005 in Northern Ireland were followed-up until 2016. Results: A
      total of 328 patients were eligible. Of them, 96 were overweight with a BMI 25.0
      29.9 kg/m2, and 56 were obese with a BMI exceeding 29.9 kg/m2. Median follow-up
      time was 16.7 years. In multivariate analysis recipient BMI was associated with
      the development of post-transplant diabetes mellitus (P=0.003), but not with new
      cardiovascular disease (P=0.78). Cancer was less common in recipients with a
      higher BMI (hazard ratio (HR) 0.58, P < 0.001). BMI at the time of
      transplantation did not significantly influence graft (P=0.28) or recipient
      survival (P=0.13). Conclusions: Increased BMI at time of transplantation is
      associated with an increased risk of post-transplant diabetes mellitus but not
      new cardiovascular disease or malignancy. Long-term graft and recipient survival
      is not impacted. Potential recipients should not be excluded from transplantation
      solely on the basis of obesity, rather it should be considered as one part of an
      individualized risk stratification, based on comorbidity and considering the risk
      of death on maintenance dialysis.

PMID- 29329415
TI  - Establishment of a three-dimensional model to study human uterine angiogenesis.
AB  - STUDY QUESTION: Can primary human uterine microvascular endothelial cells
      (UtMVECs) be used as a model to study uterine angiogenic responses in vitro that
      are relevant in pregnancy? SUMMARY ANSWER: UtMVECs demonstrated angiogenic
      responses when stimulated with proangiogenic factors, including sphingosine 1
      phosphate (S1P), vascular endothelial growth factor (VEGF), basic fibroblast
      growth factor (bFGF), physiological levels of wall shear stress (WSS), human
      chorionic gonadotropin (hCG) and various combinations of estrogen and
      progesterone. WHAT IS KNOWN ALREADY: During sprouting angiogenesis, signaling
      from growth factors and cytokines induces a monolayer of quiescent endothelial
      cells (ECs) lining the vasculature to degrade the extracellular matrix and invade
      the surrounding tissue to form new capillaries. During pregnancy and the female
      reproductive cycle, the uterine endothelium becomes activated and undergoes
      sprouting angiogenesis to increase the size and number of blood vessels in the
      endometrium. STUDY DESIGN, SIZE, DURATION: The study was designed to examine the
      angiogenic potential of primary human UtMVECs using the well-characterized human
      umbilical vein EC (HUVEC) line as a control to compare angiogenic potential. ECs
      were seeded onto three-dimensional (3D) collagen matrices, supplemented with
      known proangiogenic stimuli relevant to pregnancy and allowed to invade for 24 h.
      Sprouting responses were analyzed using manual and automated methods for
      quantification. PARTICIPANTS/MATERIALS, SETTING, METHODS: RT-PCR, Western blot
      analysis and immunostaining were used to characterize UtMVECs. Angiogenic
      responses were examined using 3D invasion assays. Western blotting was used to
      confirm signaling responses after proangiogenic lipid, pharmacological inhibitor,
      and recombinant lentiviral treatments. All experiments were repeated at least
      three times. MAIN RESULTS AND THE ROLE OF CHANCE: After ensuring that UtMVECs
      expressed the proper endothelial markers, we found that UtMVECs invade 3D
      collagen matrices dose-dependently in response to known proangiogenic stimuli
      (e.g. S1P, VEGF, bFGF, hCG, estrogen, progesterone and WSS) present during early
      pregnancy. Invasion responses were positively correlated with phosphorylation of
      phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) and p42/p44 mitogen
      activated protein kinase (ERK). Inhibition of these second messengers
      significantly impaired sprouting (P < 0.01). Gene silencing of membrane type 1
      matrix metalloproteinase using multiple approaches completely abrogated sprouting
      (P < 0.001). Finally, UtMVECs displayed a unique ability to undergo sprouting in
      response to hCG, and combined estrogen and progesterone treatment. LARGE SCALE
      DATA: Not applicable. LIMITATIONS, REASONS FOR CAUTION: The study of uterine
      angiogenesis in vitro has limitations and any findings many not fully represent
      the in vivo state. However, these experiments do provide evidence for the ability
      of UtMVECs to be used in functional sprouting assays in a 3D environment,
      stimulated by physiological factors that are produced locally within the uterus
      during early pregnancy. WIDER IMPLICATIONS OF THE FINDINGS: We show that UtMVECs
      can be used reliably to investigate how growth factors, hormones, lipids and
      other factors, such as flow, affect angiogenesis in the uterus. STUDY
      FUNDING/COMPETING INTERESTS: This work was supported by NIH award HL095786 to
      K.J.B. The authors have no conflicts of interest.

PMID- 29329416
TI  - Automatic, electrocardiographic-based detection of autonomic arousals and their
      association with cortical arousals, leg movements, and respiratory events in
      sleep.
AB  - Study Objectives: The current definition of sleep arousals neglects to address
      the diversity of arousals and their systemic cohesion. Autonomic arousals (AA)
      are autonomic activations often associated with cortical arousals (CA), but they
      may also occur in relation to a respiratory event, a leg movement event or
      spontaneously, without any other physiological associations. AA should be
      acknowledged as essential events to understand and explore the systemic
      implications of arousals. Methods: We developed an automatic AA detection
      algorithm based on intelligent feature selection and advanced machine learning
      using the electrocardiogram. The model was trained and tested with respect to CA
      systematically scored in 258 (181 training size/77 test size) polysomnographic
      recordings from the Wisconsin Sleep Cohort. Results: A precision value of 0.72
      and a sensitivity of 0.63 were achieved when evaluated with respect to CA.
      Further analysis indicated that 81% of the non-CA-associated AAs were associated
      with leg movement (38%) or respiratory (43%) events. Conclusions: The presented
      algorithm shows good performance when considering that more than 80% of the false
      positives (FP) found by the detection algorithm appeared in relation to either
      leg movement or respiratory events. This indicates that most FP constitute
      autonomic activations that are indistinguishable from those with cortical
      cohesion. The proposed algorithm provides an automatic system trained in a
      clinical environment, which can be utilized to analyze the systemic and clinical
      impacts of arousals.

PMID- 29329418
TI  - Variability of Late-Night Salivary Cortisol in Cushing Disease: A Prospective
      Study.
AB  - Background: The frequency of variable hormonogenesis in patients with Cushing
      disease (CD) but without cyclical symptoms is unclear. Aim: To assess the
      frequency of variable hormonogenesis in patients presenting with CD. Methods:
      Over a 6-month period, patients with confirmed or suspected CD provided late
      night salivary samples for up to 42 consecutive nights. Results: Of 19 patients
      confirmed to have CD, 16 provided at least 7 consecutive salivary samples, and 13
      provided at least 21; these 16 patients are the subjects of this report. Twelve
      patients had at least three peak and two trough levels of late-night salivary
      cortisol (LNSC) but in only two patients were strict criteria for cyclical
      hormonogenesis fulfilled; variation was assessed as random in the others. Eight
      patients had de novo CD, and eight had recurrent/persistent disease. All patients
      with recurrent/persistent CD had two or more normal results, and in four of these
      patients, >50% of LNSC were normal. In six patients with de novo disease with at
      least one normal LNSC level, the maximum levels ranged from 1.55 to 15.5 times
      the upper limit of normal. Conclusions: Extreme fluctuations of cortisol
      production, measured by sequential LNSC, are common in CD. In newly diagnosed
      disease, this may only occasionally impair diagnostic ability, whereas in most
      patients with recurrent/persistent disease after pituitary surgery, LNSC is
      frequently within the reference range, with potential to cause diagnostic
      problems.

PMID- 29329417
TI  - Effects of Alcohol Cues on MRS Glutamate Levels in the Anterior Cingulate.
AB  - Growing evidence suggests that glutamate neurotransmission plays a critical role
      in alcohol addiction. Cue-induced change of glutamate has been observed in animal
      studies but never been investigated in humans. This work investigates cue-induced
      change in forebrain glutamate in individuals with alcohol use disorder (AUD). A
      total of 35 subjects (17 individuals with AUD and 18 healthy controls)
      participated in this study. The glutamate concentration was measured with single
      voxel 1H-MR spectroscopy at the dorsal anterior cingulate. Two MRS sessions were
      performed in succession, the first to establish basal glutamate levels and the
      second to measure the change in response to alcohol cues. The changes in
      glutamate were quantified for both AUD subjects and controls. A mixed model ANOVA
      and t-tests were performed for statistical analysis. ANOVA revealed a main effect
      of cue-induced decrease of glutamate level in the anterior cingulate cortex
      (ACC). A significant interaction revealed that only AUD subjects showed
      significant decrease of glutamate in the ACC. There were no significant group
      differences in the level of basal glutamate. However, a negative correlation was
      found between the basal glutamate level and the number of drinking days in the
      past 2 weeks for the AUD subjects. Collectively, our results indicate that
      glutamate in key areas of the forebrain reward circuit is modulated by alcohol
      cues in early alcohol dependence.

PMID- 29329419
TI  - A Single Mutation Unlocks Cascading Exaptations in the Origin of a Potent
      Pitviper Neurotoxin.
AB  - Evolutionary innovations and complex phenotypes seemingly require an improbable
      amount of genetic change to evolve. Rattlesnakes display two dramatically
      different venom phenotypes. Type I venoms are hemorrhagic with low systemic
      toxicity and high expression of tissue-destroying snake venom metalloproteinases.
      Type II venoms are highly neurotoxic and lack snake venom metalloproteinase
      expression and associated hemorrhagic activity. This dichotomy hinges on Mojave
      toxin (MTx), a phospholipase A2 (PLA2) based beta-neurotoxin expressed in Type II
      venoms. MTx is comprised of a nontoxic acidic subunit that undergoes extensive
      proteolytic processing and allosterically regulates activity of a neurotoxic
      basic subunit. Evolution of the acidic subunit presents an evolutionary challenge
      because the need for high expression of a nontoxic venom component and the
      proteolytic machinery required for processing suggests genetic changes of
      seemingly little immediate benefit to fitness. We showed that MTx evolved through
      a cascading series of exaptations unlocked by a single nucleotide change. The
      evolution of one new cleavage site in the acidic subunit unmasked buried cleavage
      sites already present in ancestral PLA2s, enabling proteolytic processing. Snake
      venom serine proteases, already present in the venom to disrupt prey hemostasis,
      possess the requisite specificities for MTx acidic subunit proteolysis. The
      dimerization interface between MTx subunits evolved by exploiting a latent, but
      masked, hydrophobic interaction between ancestral PLA2s. The evolution of MTx
      through exaptation of existing functional and structural features suggests
      complex phenotypes that depend on evolutionary innovations can arise from minimal
      genetic change enabled by prior evolution.

PMID- 29329421
TI  - Beta-2 microglobulin clearance in high-flux dialysis and convective dialysis
      modalities: a meta-analysis of published studies.

PMID- 29329420
TI  - Pyrrolidine dithiocarbamate reverses Bcl-xL-mediated apoptotic resistance to
      doxorubicin by inducing paraptosis.
AB  - Elevated Bcl-xL expression in cancer cells contributes to doxorubicin (DOX)
      resistance, leading to failure in chemotherapy. In addition, the clinical use of
      high-dose doxorubicin (DOX) in cancer therapy has been limited by issues with
      cardiotoxicity and hepatotoxicity. Here, we show that co-treatment with
      pyrrolidine dithiocarbamate (PDTC) attenuates DOX-induced apoptosis in Chang-L
      liver cells and human hepatocytes, but overcomes DOX resistance in Bcl-xL
      overexpressing Chang-L cells and several hepatocellular carcinoma (HCC) cell
      lines with high Bcl-xL expression. Additionally, combined treatment with DOX and
      PDTC markedly retarded tumor growth in a Huh-7 HCC cell xenograft tumor model,
      compared to either mono-treatment. These results suggest that DOX/PDTC co
      treatment may provide a safe and effective therapeutic strategy against malignant
      hepatoma cells with Bcl-xL-mediated apoptotic defects. We also found that
      induction of paraptosis, a cell death mode that is accompanied by dilation of the
      endoplasmic reticulum and mitochondria, is involved in this anti-cancer effect of
      DOX/PDTC. The intracellular glutathione levels were reduced in Bcl-xL
      overexpressing Chang-L cells treated with DOX/PDTC, and DOX/PDTC-induced
      paraptosis was effectively blocked by pretreatment with thiol-antioxidants, but
      not by non-thiol antioxidants. Collectively, our results suggest that disruption
      of thiol homeostasis may critically contribute to DOX/PDTC-induced paraptosis in
      Bcl-xL-overexpressing cells.

PMID- 29329422
TI  - Proscriptive vs. Prescriptive Health Recommendations to Drink Alcohol Within
      Recommended Limits: Effects on Moral Norms, Reactance, Attitudes, Intentions and
      Behaviour Change.
AB  - Aims: Health advice can be framed in terms of prescriptive rules (what people
      should do, e.g. you should drink alcohol within recommended limits) or
      proscriptive rules (what people should not do, e.g. you should not drink alcohol
      above recommended limits). The current research examines the differing effect
      that these two types of injunction have on participants' moral norms, reactance,
      attitudes and intentions to consume alcohol within moderation, and their
      subsequent alcohol consumption. Methods: Participants (N = 529) completed an
      online questionnaire which asked them to report their previous 7 days' alcohol
      consumption. They then read either a proscriptive or a prescriptive health
      message and completed measures of moral norms, reactance, attitudes and
      intentions to drink alcohol only within recommended limits. Subsequent alcohol
      consumption was reported 7 days later. Results: The results showed that across
      all participants, the proscriptive message elicited stronger moral norms than did
      the prescriptive message, which in turn were associated with more positive
      attitudes and intentions to drink within recommended limits. For male
      participants who reported drinking more alcohol than recommended at baseline, the
      proscriptive message elicited more reported alcohol consumption over the
      subsequent 7 days. Conclusions: Proscriptive messages may be effective at
      eliciting stronger moral norms to drink within government recommended guidelines.
      However, reactance may occur for high relevance groups. Practical and theoretical
      implications are discussed.

PMID- 29329423
TI  - Development and early validation of a patient-reported outcome measure to assess
      sleep amongst people experiencing problems with alcohol or other drugs.
AB  - Study Objectives: To develop a patient-reported outcome measure to assess sleep
      amongst people experiencing problems with alcohol or other drugs. Methods: Item
      development included secondary analyses of qualitative interviews with drug or
      alcohol users in residential treatment, a review of validated sleep measures,
      focus groups with drug or alcohol users in residential treatment, and feedback
      from drug or alcohol users recruited from community and residential settings. An
      initial version of the measure was completed by 549 current and former drug or
      alcohol users (442 in person and 107 online). Analyses comprised classical test
      theory methods, exploratory and confirmatory factor analysis, measurement
      invariance assessment, and item response theory (IRT). Results: The initial
      measure (30 items) had good content and face validity and was named the Substance
      Use Sleep Scale (SUSS) by addiction service users. After seven items were removed
      due to low item-factor loadings, two factors were retained and labeled: "Mind and
      Body Sleep Problems" (14 items) and "Substance-Related Sleep Problems" (nine
      items). Measurement invariance was confirmed with respect to gender, age, and
      administration format. IRT (information) and classical test theory (internal
      consistency and stability) indicated measure reliability. Standard parametric and
      nonparametric techniques supported convergent and discriminant validity.
      Conclusions: SUSS is an easy-to-complete patient-reported outcome measure of
      sleep for people with drug or alcohol problems. It can be used by those concerned
      about their own sleep, and by treatment providers and researchers seeking to
      better understand, assess, and potentially treat sleep difficulties amongst this
      population. Further validity testing with larger and more diverse samples is now
      required.

PMID- 29329424
TI  - Brassinosteroids regulate pavement cell growth by mediating BIN2-induced
      microtubule stabilization.
AB  - Brassinosteroids (BRs), a group of plant steroid hormones, play important roles
      in regulating plant development. The cytoskeleton also affects key developmental
      processes and a deficiency in BR biosynthesis or signaling leads to abnormal
      phenotypes similar to those of microtubule-defective mutants. However, how BRs
      regulate microtubule and cell morphology remains unknown. Here, using liquid
      chromatography-tandem mass spectrometry, we identified tubulin proteins that
      interact with Arabidopsis BRASSINOSTEROID INSENSITIVE2 (BIN2), a negative
      regulator of BR responses in plants. In vitro and in vivo pull-down assays
      confirmed that BIN2 interacts with tubulin proteins. High-speed co-sedimentation
      assays demonstrated that BIN2 also binds microtubules. The Arabidopsis genome
      also encodes two BIN2 homologs, BIN2-LIKE 1 (BIL1) and BIL2, which function
      redundantly with BIN2. In the bin2-3 bil1 bil2 triple mutant, cortical
      microtubules were more sensitive to treatment with the microtubule-disrupting
      drug oryzalin than in wild-type, whereas in the BIN2 gain-of-function mutant bin2
      1, cortical microtubules were insensitive to oryzalin treatment. These results
      provide important insight into how BR regulates plant pavement cell and leaf
      growth by mediating the stabilization of microtubules by BIN2.

PMID- 29329426
TI  - A Practical Guide to Estimating the Heritability of Pathogen Traits.
AB  - Pathogen traits, such as the virulence of an infection, can vary significantly
      between patients. A major challenge is to measure the extent to which genetic
      differences between infecting strains explain the observed variation of the
      trait. This is quantified by the trait's broad-sense heritability, H2. A recent
      discrepancy between estimates of the heritability of HIV-virulence has opened a
      debate on the estimators' accuracy. Here, we show that the discrepancy originates
      from model limitations and important lifecycle differences between sexually
      reproducing organisms and transmittable pathogens. In particular, current
      quantitative genetics methods, such as donor-recipient regression (DR) of
      surveyed serodiscordant couples and the phylogenetic mixed model (PMM), are prone
      to underestimate H2, because they neglect or do not fit to the loss of
      resemblance between transmission partners caused by within-host evolution. In a
      phylogenetic analysis of 8,483 HIV patients from the UK, we show that the
      phenotypic correlation between transmission partners decays with the amount of
      within-host evolution of the virus. We reproduce this pattern in toy-model
      simulations and show that a phylogenetic Ornstein-Uhlenbeck model (POUMM)
      outperforms the PMM in capturing this correlation pattern and in quantifying H2.
      In particular, we show that POUMM outperforms PMM even in simulations without
      selection - as it captures the mentioned correlation pattern - which has not been
      appreciated until now. By cross-validating the POUMM estimates with ANOVA on
      closest phylogenetic pairs (ANOVA-CPP), we obtain H2~0.2, meaning about 20% of
      the variation in HIV-virulence is explained by the virus genome both for European
      and African data.

PMID- 29329425
TI  - Comparison of Hepatic 2D Sandwich Cultures and 3D Spheroids for Long-term
      Toxicity Applications: A Multicenter Study.
AB  - Primary human hepatocytes (PHHs) are commonly used for in vitro studies of drug
      induced liver injury. However, when cultured as 2D monolayers, PHH lose crucial
      hepatic functions within hours. This dedifferentiation can be ameliorated when
      PHHs are cultured in sandwich configuration (2Dsw), particularly when cultures
      are regularly re-overlaid with extracellular matrix, or as 3D spheroids. In this
      study, the 6 participating laboratories evaluated the robustness of these 2 model
      systems made from cryopreserved PHH from the same donors considering both inter
      donor and inter-laboratory variability and compared their suitability for use in
      repeated-dose toxicity studies using 5 different hepatotoxins with different
      toxicity mechanisms. We found that expression levels of proteins involved in drug
      absorption, distribution, metabolism, and excretion, as well as catalytic
      activities of 5 different CYPs, were significantly higher in 3D spheroid
      cultures, potentially affecting the exposure of the cells to drugs and their
      metabolites. Furthermore, global proteomic analyses revealed that PHH in 3D
      spheroid configuration were temporally stable whereas proteomes from the same
      donors in 2Dsw cultures showed substantial alterations in protein expression
      patterns over the 14 days in culture. Overall, spheroid cultures were more
      sensitive to the hepatotoxic compounds investigated, particularly upon long-term
      exposures, across testing sites with little inter-laboratory or inter-donor
      variability. The data presented here suggest that repeated-dosing regimens
      improve the predictivity of in vitro toxicity assays, and that PHH spheroids
      provide a sensitive and robust system for long-term mechanistic studies of drug
      induced hepatotoxicity, whereas the 2Dsw system has a more dedifferentiated
      phenotype and lower sensitivity to detect hepatotoxicity.

PMID- 29329427
TI  - Ozone-Induced Vascular Contractility and Pulmonary Injury Are Differentially
      Impacted by Diets Enriched With Coconut Oil, Fish Oil, and Olive Oil.
AB  - Fish, olive, and coconut oil dietary supplementation have several
      cardioprotective benefits, but it is not established if they protect against air
      pollution-induced adverse effects. We hypothesized that these dietary supplements
      would attenuate ozone-induced systemic and pulmonary effects. Male Wistar Kyoto
      rats were fed either a normal diet, or a diet supplemented with fish, olive, or
      coconut oil for 8 weeks. Animals were then exposed to air or ozone (0.8 ppm), 4
      h/day for 2 days. Ozone exposure increased phenylephrine-induced aortic
      vasocontraction, which was completely abolished in rats fed the fish oil diet.
      Despite this cardioprotective effect, the fish oil diet increased baseline levels
      of bronchoalveolar lavage fluid (BALF) markers of lung injury and inflammation.
      Ozone-induced pulmonary injury/inflammation were comparable in rats on normal,
      coconut oil, and olive oil diets with altered expression of markers in animals
      fed the fish oil diet. Fish oil, regardless of exposure, led to enlarged, foamy
      macrophages in the BALF that coincided with decreased pulmonary mRNA expression
      of cholesterol transporters, cholesterol receptors, and nuclear receptors. Serum
      microRNA profile was assessed and demonstrated marked depletion of a variety of
      microRNAs in animals fed the fish oil diet, several of which were of splenic
      origin. No ozone-specific changes were noted. Collectively, these data indicate
      that although fish oil offered vascular protection from ozone exposure, it
      increased pulmonary injury/inflammation and impaired lipid transport mechanisms
      resulting in foamy macrophage accumulation, demonstrating the need to be
      cognizant of potential off-target pulmonary effects that might offset the overall
      benefit of this vasoprotective supplement.

PMID- 29329428
TI  - Perceived environmental barriers to physical activity in young adults in Dhaka
      City, Bangladesh-does gender matter?
AB  - Background: Physical activity (PA) has demonstrated health benefits, but
      participation is low in many countries. Little is known about environmental
      barriers to PA among young Asian adults. The purpose of this study was to
      identify common perceived environmental barriers to PA in young adults in Dhaka,
      Bangladesh and to examine if these barriers differed by gender. Methods: This was
      a cross-sectional study with a self-administered survey and data collected from a
      convenience sample of 573 students aged 20.71+/-1.35 years (female 45%) in Dhaka.
      Binary logistic regression analysis was used to examine the association between
      environmental barriers and gender, adjusting for potential confounders. Results:
      Poor street lighting at night (62%) and a lack of convenient places to do PA
      (56%) were the most frequently reported environmental barriers to PA. Females
      were more likely than males to identify a lack of neighbourhood safety (OR 4.65
      [95% CI 3.09-7.00]), poor street lighting (OR 2.82 [95% CI 1.95-4.11]), lack of
      convenient places (OR 2.04 [95% CI 1.39-3.00]), unclean and untidy neighbourhood
      (OR 1.84 [95% CI 1.25-2.72]) and poor weather (OR 1.61 [95% CI 1.11-2.33]) as
      barriers to PA, after adjusting for a set of confounders. Conclusions: Findings
      suggest that environmental barriers to PA are particularly salient to young
      females in urban Bangladesh. This study underscores the need for safe and
      convenient options for PA that are also female friendly.

PMID- 29329429
TI  - How to convene an international health or development commission: ten key steps.
AB  - The Commission on Investing in Health (CIH), an international group of 25
      economists and global health experts, published its Global Health 2035 report in
      The Lancet in December 2013. The report laid out an ambitious investment
      framework for achieving a "grand convergence" in health-a universal reduction in
      deaths from infectious diseases and maternal and child health conditions-within a
      generation. This article captures ten key elements that the CIH found important
      to its process and successful outcomes. The elements are presented in
      chronological order, from inception to post-publication activities. The starting
      point is to identify the gap that a new commission could help to narrow. A
      critical early step is to choose a chair who can help to set the agenda, motivate
      the commissioners, frame the commission's analytic work, and run the commission
      meetings in an effective way. In selecting commissioners, important
      considerations are their technical expertise, ensuring diversity of people and
      viewpoints, and the connections that commissioners have with the intended policy
      audience. Financial and human resources need to be secured, typically from
      universities, foundations, and development agencies. It is important to set a
      clear end date, so that the commission's work program, the timing of its meetings
      and its interim deadlines can be established. In-person meetings are usually a
      more effective mechanism than conference calls for gaining commissioners' inputs,
      surfacing important debates, and 'reality testing' the commission's key findings
      and messages. To have policy impact, the commission report should ideally say
      something new and unexpected and should have simple messages. Generating new
      empirical data and including forward-looking recommendations can also help
      galvanize policy action. Finally, the lifespan of a commission can be extended if
      it lays the foundation for a research agenda that is then taken up after the
      commission report is published.

PMID- 29329431
TI  - A Validated Method for the Screening of 320 Forensically Significant Compounds in
      Blood by LC/QTOF, with Simultaneous Quantification of Selected Compounds.
AB  - A broad drug screening method for toxicologically significant drugs and
      metabolites in whole blood using liquid chromatography time-of-flight mass
      spectrometry (LC/QTOF) was developed and comprehensively validated. The method
      qualitatively screens for 320 compounds while simultaneously quantifying 39.
      Compounds were extracted from the blood using alkaline liquid/liquid extraction
      and chromatographic separation was achieved in 12 min. The QTOF was operated
      using positive mode electrospray ionization using data dependent acquisition.
      Qualitative validation was performed for all 320 compounds, and included
      selectivity, recovery, limit of detection, matrix effects, carryover and extract
      stability. The limits of detection were in the low to sub ng/mL range for the
      majority of compounds. Full quantitative validation was performed for 39
      compounds and accuracy and precision were within 15 and 18%, respectively. The
      qualitative data processing method uses an in-house retention time, accurate mass
      and MSMS spectral database, which can be easily updated with new compounds of
      interest as they emerge onto the market, without affecting method performance.
      The use of a non-targeted data acquisition method coupled with targeted data
      processing has proven to be a highly versatile, efficient and robust approach to
      screening, well suited to meet the needs of the modern toxicology laboratory
      involved in systematic toxicological analysis.

PMID- 29329432
TI  - Cardiac surgical strategy for extremely low-birthweight infants with pulmonary
      overcirculation.
AB  - OBJECTIVES: This study aimed to review the clinical outcomes of staged cardiac
      surgery in extremely low-birthweight infants with congenital heart disease and
      pulmonary overcirculation. METHODS: Six extremely low-birthweight infants with
      congenital heart disease and pulmonary overcirculation underwent staged cardiac
      surgery between 2005 and 2017. The median birthweight was 895 g (range 620-990
      g), and the median gestational age was 28 weeks (range 23-31 weeks). Clinical
      outcomes were evaluated, and we focused on pulmonary haemodynamics. RESULTS:
      Pulmonary artery banding or bilateral pulmonary artery banding was performed as
      the initial palliation at a median age of 23 days with a median body weight of
      880 g. Corrective surgery was performed at a median age of 187 days with a median
      body weight of 3.9 kg. All of the patients successfully underwent corrective
      surgery and survived to date. Pulmonary hypertension regressed after corrective
      surgery in all of the patients, except for 1 patient with severe bronchopulmonary
      dysplasia. CONCLUSIONS: Acceptable outcomes can be obtained by staged cardiac
      surgery in extremely low-birthweight infants with congenital heart disease and
      pulmonary overcirculation. While early pulmonary artery banding can lead to
      regression of pulmonary hypertension after corrective surgery, close follow-up is
      required.

PMID- 29329430
TI  - Increases in IGF-1 After Anti-TNF-alpha Therapy Are Associated With Bone and
      Muscle Accrual in Pediatric Crohn Disease.
AB  - Context: Low levels of insulinlike growth factor 1 (IGF-1) in pediatric and
      adolescent Crohn disease (CD) likely contribute to bone and muscle deficits.
      Objective: Assess changes in IGF-1 levels and associations with bone and muscle
      accrual following initiation of anti-tumor necrosis factor alpha (TNF-alpha)
      therapy in pediatric and adolescent CD. Design and Participants: Participants (n
      = 75, age 5 to 21 years) with CD were enrolled in a prospective cohort study; 63
      completed the 12-month visit. Main Outcome Measures: IGF-1 levels at baseline and
      10 weeks, as well as dual-energy x-ray absorptiometry (DXA) and tibia peripheral
      quantitative computed tomography (pQCT) measures of bone and muscle at baseline
      and 12 months after initiation of anti-TNF-alpha therapy. Outcomes were expressed
      as sex-specific z scores. Results: IGF-1 z scores increased from a median
      (interquartile range) of -1.0 (-1.58 to -0.17) to -0.36 (-1.04 to 0.36) over 10
      weeks (P < 0.001). Lesser disease severity and systemic inflammation, as well as
      greater estradiol z scores (in girls), was significantly associated with greater
      IGF-1 z scores over time. DXA whole-body bone mineral content, leg lean mass, and
      total hip and femoral neck bone mineral density (BMD) z scores were low at
      baseline (P < 0.0001 vs reference data) and increased significantly (P < 0.001)
      over 12 months. Greater increases in IGF-1 z scores over 10 weeks predicted
      improvement in DXA bone and muscle outcomes and pQCT trabecular BMD and cortical
      area. Adjustment for changes in muscle mass markedly attenuated the associations
      between IGF-1 levels and bone outcomes. Conclusions: Short-term improvements in
      IGF-1 z scores predicted recovery of bone and muscle outcomes following
      initiation of anti-TNF-alpha therapy in pediatric CD. These data suggest that
      disease effects on growth hormone metabolism contribute to musculoskeletal
      deficits in CD.

PMID- 29329433
TI  - RAGE mediates Abeta accumulation in a mouse model of Alzheimer's disease via
      modulation of beta- and gamma-secretase activity.
AB  - Receptor for Advanced Glycation End products (RAGE) has been implicated in
      amyloid beta-peptide (Abeta)-induced perturbation relevant to the pathogenesis of
      Alzheimer's disease (AD). However, whether and how RAGE regulates Abeta
      metabolism remains largely unknown. Abeta formation arises from aberrant cleavage
      of amyloid pre-cursor protein (APP) by beta- and gamma-secretase. To investigate
      whether RAGE modulates beta- and gamma-secretase activity potentiating Abeta
      formation, we generated mAPP mice with genetic deletion of RAGE (mAPP/RO). These
      mice displayed reduced cerebral amyloid pathology, inhibited aberrant APP-Abeta
      metabolism by reducing beta- and gamma-secretases activity, and attenuated
      impairment of learning and memory compared with mAPP mice. Similarly, RAGE signal
      transduction deficient mAPP mice (mAPP/DN-RAGE) exhibited the reduction in
      Abeta40 and Abeta42 production and decreased beta-and gamma-secretase activity
      compared with mAPP mice. Furthermore, RAGE-deficient mAPP brain revealed
      suppression of activation of p38 MAP kinase and glycogen synthase kinase 3beta
      (GSK3beta). Finally, RAGE siRNA-mediated gene silencing or DN-RAGE-mediated
      signaling deficiency in the enriched human APP neuronal cells demonstrated
      suppression of activation of GSK3beta, accompanied with reduction in Abeta levels
      and decrease in beta- and gamma-secretases activity. Our findings highlight that
      RAGE-dependent signaling pathway regulates beta- and gamma-secretase cleavage of
      APP to generate Abeta, at least in part through activation of GSK3beta and p38
      MAP kinase. RAGE is a potential therapeutic target to limit aberrant APP-Abeta
      metabolism in halting progression of AD.

PMID- 29329434
TI  - Effect of mechanical stress on magnetic resonance imaging of the sacroiliac
      joints: assessment of military recruits by magnetic resonance imaging study.

PMID- 29329435
TI  - Expanding a radiology lexicon using contextual patterns in radiology reports.
AB  - Objective: Distributional semantics algorithms, which learn vector space
      representations of words and phrases from large corpora, identify related terms
      based on contextual usage patterns. We hypothesize that distributional semantics
      can speed up lexicon expansion in a clinical domain, radiology, by unearthing
      synonyms from the corpus. Materials and Methods: We apply word2vec, a
      distributional semantics software package, to the text of radiology notes to
      identify synonyms for RadLex, a structured lexicon of radiology terms. We
      stratify performance by term category, term frequency, number of tokens in the
      term, vector magnitude, and the context window used in vector building. Results:
      Ranking candidates based on distributional similarity to a target term results in
      high curation efficiency: on a ranked list of 775 249 terms, >50% of synonyms
      occurred within the first 25 terms. Synonyms are easier to find if the target
      term is a phrase rather than a single word, if it occurs at least 100* in the
      corpus, and if its vector magnitude is between 4 and 5. Some RadLex categories,
      such as anatomical substances, are easier to identify synonyms for than others.
      Discussion: The unstructured text of clinical notes contains a wealth of
      information about human diseases and treatment patterns. However, searching and
      retrieving information from clinical notes often suffer due to variations in how
      similar concepts are described in the text. Biomedical lexicons address this
      challenge, but are expensive to produce and maintain. Distributional semantics
      algorithms can assist lexicon curation, saving researchers time and money.

PMID- 29329436
TI  - Development of the place-based Adelante social marketing campaign for prevention
      of substance use, sexual risk and violence among Latino immigrant youth.
AB  - Immigrant Latino youth represent a high-risk subgroup that should be targeted
      with health promotion efforts. However, there are considerable barriers to
      engagement in health-related programming. Little is known about the engagement
      possibilities of social marketing campaigns and digital strategies for
      traditionally 'hard-to-reach' immigrants, underscoring the importance of testing
      these techniques with immigrant Latino adolescents. We developed and piloted a
      place-based social marketing campaign in coordination with the branded, Positive
      Youth Development-based (PYD) Adelante intervention targeting risk factors for co
      occurring youth substance abuse, sexual risk and violence. Building on prior
      research, we conducted a four-phase formative research process, and planned the
      Adelante social marketing campaign based on findings from one group interview and
      ongoing consultation with Adelante staff (n=8) and four focus groups with youth
      (n=35). Participants identified four overarching campaign themes, and suggested
      portrayal of resilient, proud youth who achieved goals despite adversity. Youth
      guided selection of campaign features and engagement strategies, including
      message/visual content, stylistic elements, and a mixed language approach. We
      developed a 12-month campaign to be delivered via print ads, multi-platform
      social media promotion, contests, youth-generated videos, blog posts, and text
      messaging. We describe the process and outcome of campaign development and make
      recommendations for future campaigns.

PMID- 29329437
TI  - Association of extracellular dNTP utilization with a GmPAP1-like protein
      identified in cell wall proteomic analysis of soybean roots.
AB  - Plant root cell walls are dynamic systems that serve as the first plant
      compartment responsive to soil conditions, such as phosphorus (P) deficiency. To
      date, evidence for the regulation of root cell wall proteins (CWPs) by P
      deficiency remains sparse. In order to gain a better understanding of the roles
      played by CWPs in the roots of soybean (Glycine max) in adaptation to P
      deficiency, we conducted an iTRAQ (isobaric tag for relative and absolute
      quantitation) proteomic analysis. A total of 53 CWPs with differential
      accumulation in response to P deficiency were identified. Subsequent qRT-PCR
      analysis correlated the accumulation of 21 of the 27 up-regulated proteins, and
      eight of the 26 down-regulated proteins with corresponding gene expression
      patterns in response to P deficiency. One up-regulated CWP, purple acid
      phosphatase 1-like (GmPAP1-like), was functionally characterized. Phaseolus
      vulgaris transgenic hairy roots overexpressing GmPAP1-like displayed an increase
      in root-associated acid phosphatase activity. In addition, relative growth and P
      content were significantly enhanced in GmPAP1-like overexpressing lines compared
      to control lines when deoxy-ribonucleotide triphosphate (dNTP) was applied as the
      sole external P source. Taken together, the results suggest that the modulation
      of CWPs may regulate complex changes in the root system in response to P
      deficiency, and that the cell wall-localized GmPAP1-like protein is involved in
      extracellular dNTP utilization in soybean.

PMID- 29329438
TI  - Patient perspectives on how physicians communicate diagnostic uncertainty: An
      experimental vignette study.
AB  - Objective: We evaluated the effects of three different strategies for
      communicating diagnostic uncertainty on patient perceptions of physician
      competence and visit satisfaction. Design/Setting: Experimental vignette-based
      study design involving pediatric cases presented to a convenience sample of
      parents living in a large US city. Participants/Intervention(s): Three vignettes
      were developed, each describing one of three different ways physicians
      communicated diagnostic uncertainty to parents-(i) explicit expression of
      uncertainty ('not sure' about diagnosis), (ii) implicit expression of uncertainty
      using broad differential diagnoses and (iii) implicit expression of uncertainty
      using 'most likely' diagnoses. Participants were randomly assigned to one of the
      three vignettes and then answered a 37-item web-based questionnaire. Main Outcome
      Measure(s): Outcome variables included parent-perceived technical competence of
      physician, trust and confidence, visit satisfaction and adherence to physician
      instructions. Differences between the three groups were compared using analysis
      of variance, followed by individual post hoc analyses with Bonferroni correction.
      Results: Seventy-one participants completed the vignette questions. Demographic
      characteristics and scores on activation (parent activation measure [PAM]) and
      intolerance to uncertainty were similar across the three groups. Explicit
      expression of uncertainty was associated with lower perceived technical
      competence, less trust and confidence, and lower patient adherence as compared to
      the two groups with implicit communication. These latter two groups had
      comparable outcomes. Conclusion: Parents may react less negatively in terms of
      perceived competence, physician confidence and trust, and intention to adhere
      when diagnostic uncertainty is communicated using implicit strategies, such as
      using broad differential diagnoses or most likely diagnoses. Evidence-based
      strategies to communicate diagnostic uncertainty to patients need further
      development.

PMID- 29329440
TI  - Executive Function and Internalizing Symptoms in Adolescents and Young Adults
      With Congenital Heart Disease: The Role of Coping.
AB  - Objective: Executive functioning deficits have been documented among congenital
      heart disease (CHD) survivors and may contribute to emotional distress. Little
      research has investigated the role of coping in this association. This study
      examined the role of coping in accounting for the association between self
      reported executive function problems and internalizing symptoms among adolescents
      and emerging adults (AEAs), as well as young adults (YAs) with CHD. Methods:
      Participants included 74 AEA (Mage = 19.32 +/- 3.47 years, range 15-25 years) and
      98 YA CHD survivors (Mage = 32.00 +/- 3.69 years, range 26-39 years), recruited
      from pediatric and adult outpatient cardiology clinics. Participants completed
      self-report measures of executive function problems, coping (primary control,
      secondary control, and disengagement coping), and internalizing symptoms. Lesion
      severity classification and functional impairment due to symptoms of heart
      failure were determined from medical chart review. Results: Significant problems
      in executive function were reported by 5% of AEA and 13% of YA. Coping was not
      associated with executive function problems or internalizing symptoms for AEA.
      However, among YA, less use of adaptive coping strategies and more maladaptive
      coping responses was associated with both more executive function problems and
      internalizing symptoms. An indirect effect of executive function problems on
      internalizing symptoms via secondary control coping emerged for YA. Conclusions:
      Executive function problems may disrupt the ability to use important adaptive
      coping skills, such as cognitive reappraisal, positive thinking, and acceptance,
      thereby resulting in greater emotional distress among YA CHD survivors.

PMID- 29329441
TI  - Aging and the Social Ecology of Everyday Interpersonal Perception: What is
      Perceived, in Whom, and Where?
AB  - Objectives: Despite a proliferation of research in interpersonal perception and
      aging, no research has identified the nature of the social and emotional
      perceptions made by aging individuals in everyday life. In this study, we aimed
      to identify the social ecological features that characterize everyday
      interpersonal perception across the adult lifespan. Method: Three studies were
      conducted. Study 1 identified and compared the targets and locations of young,
      middle-age, and older adults' everyday interpersonal perceptions; these
      perceptions were categorized into types in Study 2. Study 3 applied these
      categorizations to identify and compare the social ecology surrounding aging
      individuals' interpersonal perceptions. Results: Everyday interpersonal
      perceptions were directed toward familiar others and occurred in familiar
      locations, although the specific familiar targets and locations sometimes varied
      significantly with age. However, the types of perceptions made in everyday life
      did not vary significantly between age groups. Discussion: Aging individuals make
      similar types of interpersonal judgments, but the targets and locations of these
      judgments may change with age. Future studies on interpersonal perception and
      aging will need to account for these features of the aging individual's social
      ecology to provide an accurate assessment of the aging process.

PMID- 29329439
TI  - Conserved Proteins of the RNA Interference System in the Arbuscular Mycorrhizal
      Fungus Rhizoglomus irregulare Provide New Insight into the Evolutionary History
      of Glomeromycota.
AB  - Horizontal gene transfer (HGT) is an important mechanism in the evolution of many
      living organisms particularly in Prokaryotes where genes are frequently dispersed
      between taxa. Although, HGT has been reported in Eukaryotes, its accumulative
      effect and its frequency has been questioned. Arbuscular mycorrhizal fungi (AMF)
      are an early diverged fungal lineage belonging to phylum Glomeromycota, whose
      phylogenetic position is still under debate. The history of AMF and land plant
      symbiosis dates back to at least 460 Ma. However, Glomeromycota are estimated to
      have emerged much earlier than land plants. In this study, we surveyed genomic
      and transcriptomic data of the model arbuscular mycorrhizal fungus Rhizoglomus
      irregulare (synonym Rhizophagus irregularis) and its relatives to search for
      evidence of HGT that occurred during AMF evolution. Surprisingly, we found a
      signature of putative HGT of class I ribonuclease III protein-coding genes that
      occurred from autotrophic cyanobacteria genomes to R. irregulare. At least one of
      two HGTs was conserved among AMF species with high levels of sequence similarity.
      Previously, an example of intimate symbiosis between AM fungus and cyanobacteria
      was reported in the literature. Ribonuclease III family enzymes are important in
      small RNA regulation in Fungi together with two additional core proteins
      (Argonaute/piwi and RdRP). The eukaryotic RNA interference system found in AMF
      was conserved and showed homology with high sequence similarity in
      Mucoromycotina, a group of fungi closely related to Glomeromycota. Prior to this
      analysis, class I ribonuclease III has not been identified in any eukaryotes. Our
      results indicate that a unique acquisition of class I ribonuclease III in AMF is
      due to a HGT event that occurred from cyanobacteria to Glomeromycota, at the
      latest before the divergence of the two Glomeromycota orders Diversisporales and
      Glomerales.

PMID- 29329442
TI  - Conventional Radiofrequency Thermocoagulation vs Pulsed Radiofrequency
      Neuromodulation of Ganglion Impar in Chronic Perineal Pain of Nononcological
      Origin.
AB  - Background: Chronic nononcological perineal pain has been effectively managed by
      ganglion Impar block. Chemical neurolysis, cryoablation, and radiofrequency
      ablation have been the accepted methods of blockade. Recently, pulsed
      radiofrequency, a novel variant of conventional radiofrequency, has been used for
      this purpose. Study Design: This was a prospective, randomized, double-blind
      study. Setting: Two different interventional pain management centers in India.
      Objective: To compare the efficacy of conventional radiofrequency and pulsed
      radiofrequency for gangliom Impar block. Methods: The patients were randomly
      allocated to one of two groups. In the conventional radiofrequency (CRF) group (N
      = 34), conventional radiofrequency ablation was done, and in the PRF pulsed
      radiofrequency (PRF) group (N = 31), pulsed radiofrequency ablation was done.
      After informed and written consent, fluoroscopy-guided ganglion Impar block was
      performed through the first intracoccygeal approach. The extent of pain relief
      was assessed by visual analog scale (VAS) at 24 hours, and at the first, third,
      and sixth weeks following the intervention. A questionnaire to evaluate
      subjective patient satisfaction was also used at each follow-up visit. Results:
      In the CRF group, the mean VAS score decreased significantly from the baseline
      value at each follow-up visit. But in the PRF group, this decrease was
      insignificant except at 24-hour follow-up. Intergroup comparison also showed
      significantly better pain relief in the CRF group as compared with the PRF group.
      At the end of follow-up, 28 patients (82%) in the CRF group and four patients
      (13%) in the PRF group had excellent results, as assessed by the subjective
      patient satisfaction questionnaire. There was no complication in any patient of
      either study group, except for short-lived infection at the site of skin puncture
      in a few. Conclusion: Ganglion Impar block by conventional radiofrequency
      provided a significantly better quality of pain relief with no major side effects
      in patients with chronic nononcological perineal pain as compared with pulsed
      radiofrequency. Limitations: The short-term follow-up period of only six weeks
      was a major drawback associated with this study.

PMID- 29329444
TI  - Prevention of IVR: a need for investigation.
AB  - Intravesical recurrence (IVR) after RNU for UTUC is a frequent event, occurring
      in 20-50% of patients, mostly in the first postoperative year. Several
      retrospective studies have shown that predictors of IVR include clinical
      characteristics, surgical features and as well pathological characteristics
      (previous history of bladder cancer, pathological stage, lymph node involvement,
      cis, endoscopic distal ureter, etc.) management. Two prospective studies provide
      level I evidence for the safety and efficacy of intravesical single postoperative
      chemotherapy for patients treated with radical nephroureterectomy (RNU) for UTUC
      in order to prevent IVR. However, some questions remain unanswered. Yamashita et
      al. in the current issue of the journal have shown that early ureteral ligation
      during RNU decreases the risk of IVR in patients with pelvycalyceal upper tract
      urothelial carcinoma. This study despite its limitations represent a step towards
      improved outcomes for our patients with UTUC, the relatively low morbidity of the
      procedure added to the potential benefit associated with this early ligation make
      it an easy implementation in daily practice.

PMID- 29329445
TI  - Author's reply to 'Prevention of IVR: a need for investigation'.

PMID- 29329443
TI  - Bone formation in ankylosing spondylitis during anti-tumour necrosis factor
      therapy imaged by 18F-fluoride positron emission tomography.
AB  - Objectives: Excessive bone formation is an important hallmark of AS. Recently it
      has been demonstrated that axial bony lesions in AS patients can be visualized
      using 18F-fluoride PET-CT. The aim of this study was to assess whether 18F
      fluoride uptake in clinically active AS patients is related to focal bone
      formation in spine biopsies and is sensitive to change during anti-TNF treatment.
      Methods: Twelve anti-TNF-naive AS patients [female 7/12; age 39 years (SD 11);
      BASDAI 5.5 +/- 1.1] were included. 18 F-fluoride PET-CT scans were performed at
      baseline and in two patients, biopsies were obtained from PET-positive and PET
      negative spine lesions. The remaining 10 patients underwent a second 18F-fluoride
      PET-CT scan after 12 weeks of anti-TNF treatment. PET scans were scored visually
      by two blinded expert readers. In addition, 18F-fluoride uptake was quantified
      using the standardized uptake value corrected for individual integrated whole
      blood activity concentration (SUVAUC). Clinical response to anti-TNF was defined
      according to a ? 20% improvement in Assessment of SpondyloArthritis international
      Society criteria at 24 weeks. Results: At baseline, all patients showed at least
      one axial PET-positive lesion. Histological analysis of PET-positive lesions in
      the spine confirmed local osteoid formation. PET-positive lesions were found in
      the costovertebral joints (43%), facet joints (23%), bridging syndesmophytes
      (20%) and non-bridging vertebral lesions (14%) and in SI joints (75%). After 12
      weeks of anti-TNF treatment, 18F-fluoride uptake in clinical responders decreased
      significantly in the costovertebral (mean SUVAUC -1.0; P < 0.001) and SI joints
      (mean SUVAUC -1.2; P = 0.03) in contrast to non-responders. Conclusions: 18F
      fluoride PET-CT identified bone formation, confirmed by histology, in the spine
      and SI joints of AS patients and demonstrated alterations in bone formation
      during anti-TNF treatment.

PMID- 29329446
TI  - Standardisation of the in vitro comet assay: influence of lysis time and lysis
      solution composition on the detection of DNA damage induced by X-rays.
AB  - The alkaline comet assay, in vivo and in vitro, is currently used in several
      areas of research and in regulatory genotoxicity testing. Several efforts have
      been made in order to decrease the inter-experimental and inter-laboratory
      variability and increase the reliability of the assay. In this regard, lysis
      conditions are considered as one of the critical variables and need to be further
      studied. Here, we tested different times of lysis (from no lysis to 1 week) and
      two different lysis solutions in human lymphoblast (TK6) cells unexposed or
      exposed to X-rays. Similar % tail DNA values were obtained independently of the
      time of lysis employed for every X-ray dose tested and both lysis solutions.
      These results, taken together with our previous ones with methyl methanesulfonate
      and H2O2, which showed clear lysis-time dependence, support that the influence of
      the lysis time in the comet assay results depends on the type of lesion being
      detected; some DNA lesions may spontaneously give rise to apurinic or
      apyrimidinic (AP) sites during the lysis period, which can be converted into
      strand breaks detectable with the comet assay. Testing different times of lysis
      would be useful to increase the sensitivity of the comet assay and to ensure the
      detection of DNA lesions of an unknown compound, thereby providing some insight
      into the chemical nature of the lesions induced. However, the same lysis
      conditions (i.e. lysis time and lysis solution) should be used when comparing
      results between different experiments or laboratories.

PMID- 29329447
TI  - Congenital Hyperinsulinism and Hypopituitarism Attributable to a Mutation in
      FOXA2.
AB  - Context: Persistent hypoglycemia in the newborn period most commonly occurs as a
      result of hyperinsulinism. The phenotype of hypoketotic hypoglycemia can also
      result from pituitary hormone deficiencies, including growth hormone and
      adrenocorticotropic hormone deficiency. Forkhead box A2 (Foxa2) is a
      transcription factor shown in mouse models to influence insulin secretion by
      pancreatic beta cells. In addition, Foxa2 is involved in regulation of pituitary
      development, and deletions of FOXA2 have been linked to panhypopituitarism.
      Objective: To describe an infant with congenital hyperinsulinism and
      hypopituitarism as a result of a mutation in FOXA2 and to determine the
      functional impact of the identified mutation. Main Outcome Measure: Difference in
      wild-type (WT) vs mutant Foxa2 transactivation of target genes that are critical
      for beta cell function (ABCC8, KNCJ11, HADH) and pituitary development (GLI2,
      NKX2-2, SHH). Results: Transactivation by mutant Foxa2 of all genes studied was
      substantially decreased compared with WT. Conclusions: We report a mutation in
      FOXA2 leading to congenital hyperinsulinism and hypopituitarism and provide
      functional evidence of the molecular mechanism responsible for this phenotype.

PMID- 29329449
TI  - Lack of Receptor for Advanced Glycation End Products Leads to Less Severe
      Staphylococcal Skin Infection but More Skin Abscesses and Prolonged Wound
      Healing.
AB  - Background: Lack of receptor for advanced glycation end products (RAGE)
      ameliorates several infections including Staphylococcus aureus pneumonia. We
      sought to investigate the role of RAGE in staphylococcal skin infection in mice.
      Methods: Wild-type (WT) and RAGE deficient (RAGE-/-) mice were subcutaneously
      inoculated with S. aureus SH1000 strain in abscess-forming dose or necrotic dose.
      Clinical signs of dermatitis, along with histopathological changes, were compared
      between the groups. Results: The skin lesion size was smaller in RAGE-/- mice.
      Infected RAGE-/- mice expressed lower proinflammatory cytokines in local skins
      compared to control mice. Low dose of bacteria caused more abscess formation in
      RAGE-/- mice compared to skin necrosis that was more often observed in WT mice.
      As a result of more abscess formation, the wound healing was prolonged in RAGE-/-
      mice. Importantly, RAGE-/- mice had lower bacterial loads in the skin than
      controls, which is correlated with higher local levels of myeloperoxidase before
      skin infection. In vitro, enhanced phagocytic capacity of neutrophils and
      macrophages obtained from RAGE-/- mice compared to control mice was observed.
      Conclusions: RAGE deficiency up-regulates phagocytic capacity of phagocytes,
      resulting in lower bacterial burden in local skin and milder skin lesions in mice
      with staphylococcal skin infection.

PMID- 29329448
TI  - The Prevalence and Management of Dehydration amongst Neonatal Admissions to
      General Paediatric Wards in Kenya-A Clinical Audit.
AB  - An audit of randomly selected case records of 810 patients admitted to 13
      hospitals between December 2015 and November 2016 was done. Prevalence of
      dehydration was 19.7% (2293 of 11 636) [95% CI: 17.1-22.6%], range across
      hospitals was 9.4% to 27.0%. Most cases with dehydration were clinically
      diagnosed (82 of 153; 53.6%), followed by excessive weight loss (54 of 153;
      35.3%) and abnormal urea/electrolytes/creatinine (23 of 153; 15.0%).
      Documentation of fluids prescribed was poor but, where data were available,
      Ringers lactate (30 of 153; 19.6%) and 10% dextrose (18 of 153; 11.8%) were
      mostly used. Only 17 of 153 (11.1%) children had bolus fluid prescription, and
      Ringer's lactate was most commonly used for bolus at a median volume per kilogram
      body weight of 20 ml/kg (interquartile range, 12-30 ml/kg). Neonatal dehydration
      is common, but current documentation may underestimate the burden. Heterogeneity
      in practice likely reflects the absence of guidelines that in turn reflects a
      lack of research informing practical treatment guidelines.

PMID- 29329450
TI  - DEVELOPMENT OF HETEROGENEOUS PROPORTIONAL COUNTERS FOR NEUTRON DOSIMETRY.
AB  - The use of a custom-made cylindrical graphite proportional counter (Cy-GPC) along
      with a cylindrical tissue equivalent proportional counter (TEPC) for neutron
      gamma mixed-field dosimetry has been studied in the following steps: first, the
      consistency of the gamma dose measurement between the Cy-TEPC and the Cy-GPC was
      investigated over a range of 20 keV (X-ray) to 0.661 MeV (Cs-137 gamma ray).
      Then, with both the counters used simultaneously, the neutron and gamma ray doses
      produced by a P385 Neutron Generator (Thermo Fisher Scientific) together with a
      Cs-137 gamma source were determined.

PMID- 29329452
TI  - Comment on "Response assessment in medulloblastoma and leptomeningeal seeding
      tumors: recommendations from the Response Assessment in Pediatric Neuro-Oncology
      Committee".

PMID- 29329453
TI  - Response to Harreld re: "Response assessment in medulloblastoma and
      leptomeningeal seeding tumors: recommendations from the Response Assessment in
      Pediatric Neuro-Oncology Committee".

PMID- 29329451
TI  - Epidermal Growth Factor Receptor Signaling Disruption by Endocrine and Metabolic
      Disrupting Chemicals.
AB  - The purpose of this study is to identify an environmentally relevant shared
      receptor target for endocrine and metabolism disrupting chemical pollutants. A
      feature of the tested chemicals was that they induced Cyp2b10 in vivo implicating
      activation of the constitutive androstane receptor (CAR). Recent studies suggest
      that these compounds could be indirect CAR activators via epidermal growth factor
      receptor (EGFR) inhibition. Assays included a CAR activity reporter assay, EGF
      endocytosis assay, and EGFR phosphorylation assay. Docking simulations were used
      to identify putative binding sites for environmental chemicals on the EGFR. Whole
      weight and lipid-adjusted serum mean pollutant exposures were determined using
      data from the National Health and Examination Survey (NHANES) and compared with
      the IC50 values determined in vitro. Chlordane, trans-nonachlor, PCB-126, PCB
      153, and atrazine were the most potent EGFR inhibitors tested. PCB-126, PCB-153,
      and trans-nonachlor appeared to be competitive EGFR antagonists as they displaced
      bound EGF from EGFR. However, atrazine acted through a different mechanism and
      could be an EGFR tyrosine kinase inhibitor. EGFR inhibition relative effect
      potencies were determined for these compounds. In NHANES, serum concentrations of
      trans-nonachlor, PCB-126, and PCB-153 greatly exceeded their calculated IC50
      values. A common mechanism of action through EGFR inhibition for three diverse
      classes of metabolic disrupting chemicals was characterized by measuring
      inhibition of EGFR phosphorylation and EGF-EGFR endocytosis. Based on NHANES
      data, EGFR inhibition may be an environmentally relevant mode of action for some
      PCBs, pesticides, and herbicides.

PMID- 29329454
TI  - A change at the helm of Neuro-Oncology.

PMID- 29329455
TI  - Serologic Evidence of Ebolavirus Infection in a Population With No History of
      Outbreaks in the Democratic Republic of the Congo.
AB  - Background: Previous studies suggest that cases of Ebola virus disease (EVD) may
      go unreported because they are asymptomatic or unrecognized, but evidence is
      limited by study designs and sample size. Methods: A large population-based
      survey was conducted (n = 3415) to assess animal exposures and behaviors
      associated with Ebolavirus antibody prevalence in rural Kasai Oriental province
      of the Democratic Republic of Congo (DRC). Fourteen villages were randomly
      selected and all healthy individuals >=1 year of age were eligible. Results:
      Overall, 11% of subjects tested positive for Zaire Ebolavirus (EBOV)
      immunoglobulin G antibodies. Odds of seropositivity were higher for study
      participants older than 15 years of age and for males. Those residing in Kole
      (closer to the outbreak site) tested positive at a rate 1.6* higher than Lomela,
      with seropositivity peaking at a site located between Kole and Lomela.
      Multivariate analyses of behaviors and animal exposures showed that visits to the
      forest or hunting and exposure to rodents or duikers predicted a higher
      likelihood of EBOV seropositivity. Conclusions: These results provide serologic
      evidence of Ebolavirus exposure in a population residing in non-EBOV outbreak
      locations in the DRC and define statistically significant activities and animal
      exposures that associate with EBOV seropositivity.

PMID- 29329456
TI  - Designing and evaluating an automated system for real-time medication
      administration error detection in a neonatal intensive care unit.
AB  - Background: Timely identification of medication administration errors (MAEs)
      promises great benefits for mitigating medication errors and associated harm.
      Despite previous efforts utilizing computerized methods to monitor medication
      errors, sustaining effective and accurate detection of MAEs remains challenging.
      In this study, we developed a real-time MAE detection system and evaluated its
      performance prior to system integration into institutional workflows. Methods:
      Our prospective observational study included automated MAE detection of 10 high
      risk medications and fluids for patients admitted to the neonatal intensive care
      unit at Cincinnati Children's Hospital Medical Center during a 4-month period.
      The automated system extracted real-time medication use information from the
      institutional electronic health records and identified MAEs using logic-based
      rules and natural language processing techniques. The MAE summary was delivered
      via a real-time messaging platform to promote reduction of patient exposure to
      potential harm. System performance was validated using a physician-generated gold
      standard of MAE events, and results were compared with those of current practice
      (incident reporting and trigger tools). Results: Physicians identified 116 MAEs
      from 10 104 medication administrations during the study period. Compared to
      current practice, the sensitivity with automated MAE detection was improved
      significantly from 4.3% to 85.3% (P = .009), with a positive predictive value of
      78.0%. Furthermore, the system showed potential to reduce patient exposure to
      harm, from 256 min to 35 min (P < .001). Conclusions: The automated system
      demonstrated improved capacity for identifying MAEs while guarding against alert
      fatigue. It also showed promise for reducing patient exposure to potential harm
      following MAE events.

PMID- 29329457
TI  - A novel application of RNase H2-dependent quantitative PCR for detection and
      quantification of Grosmannia clavigera, a mountain pine beetle fungal symbiont,
      in environmental samples.
AB  - Mountain pine beetle (Dendroctonus ponderosae Hopkins; MPB) is an economically
      and ecologically important pest of pine species in western North America.
      Mountain pine beetles form complex multipartite relationships with microbial
      partners, including the ophiostomoid fungi Grosmannia clavigera (Robinson-Jeffrey
      and Davidson) Zipfel, de Beer and Wingfield, Ophiostoma montium (Rumbold) von
      Arx, Grosmannia aurea (Robinson-Jeffrey and Davidson) Zipfel, de Beer and
      Wingfield, Leptographium longiclavatum (Lee, Kim, and Breuil) and Leptographium
      terebrantis (Barras and Perry). These fungi are vectored by MPB to new pine
      hosts, where the fungi overcome host defenses to grow into the sapwood. A tree's
      relative susceptibility to these fungi is conventionally assessed by measuring
      lesions that develop in response to fungal inoculation. However, these lesions
      represent a symptom of infection, representing both fungal growth and tree
      defense capacity. In order to more objectively assess fungal virulence and host
      tree susceptibility in studies of host-pathogen interactions, a reliable,
      consistent, sensitive method is required to accurately identify and quantify MPB
      associated fungal symbionts in planta. We have adapted RNase H2-dependent PCR, a
      technique originally designed for rare allele discrimination, to develop a novel
      RNase H2-dependent quantitative PCR (rh-qPCR) assay that shows greater
      specificity and sensitivity than previously published PCR-based methods to
      quantify MPB fungal symbionts in pine xylem and MPB whole beetles. Two sets of
      assay probes were designed: one that amplifies a broad range of ophiostomoid
      species, and a second that amplifies G. clavigera but not other MPB-associated
      ophiostomoid species. Using these primers to quantify G. clavigera in pine stems,
      we provide evidence that lesion length does not accurately reflect the extent of
      fungal colonization along the stem nor the quantity of fungal growth within this
      colonized portion of stem. The sensitivity, specificity, reproducibility, cost
      effectiveness and high-throughput potential of the rh-qPCR assay makes the
      technology suitable for identification and quantification of a wide array of
      pathogenic and beneficial microbes that form associations with plants and other
      organisms, even when the microbial partner is present in low abundance.

PMID- 29329459
TI  - Using Pool-seq to Search for Genomic Regions Affected by Hybrid Inviability in
      the copepod T. californicus.
AB  - The formation of reproductive barriers between allopatric populations involves
      the accumulation of incompatibilities that lead to intrinsic postzygotic
      isolation. The evolution of these incompatibilities is usually explained by the
      Dobzhansky-Muller model, where epistatic interactions that arise within the
      diverging populations, lead to deleterious interactions when they come together
      in a hybrid genome. These incompatibilities can lead to hybrid inviability,
      killing individuals with certain genotypic combinations, and causing the
      population's allele frequency to deviate from Mendelian expectations.
      Traditionally, hybrid inviability loci have been detected by genotyping
      individuals at different loci across the genome. However, this method becomes
      time consuming and expensive as the number of markers or individuals increases.
      Here, we test if a Pool-seq method can be used to scan the genome of F2 hybrids
      to detect genomic regions that are affected by hybrid inviability. We survey the
      genome of hybrids between 2 populations of the copepod Tigriopus californicus,
      and show that this method has enough power to detect even small changes in allele
      frequency caused by hybrid inviability. We show that allele frequency estimates
      in Pool-seq can be affected by the sampling of alleles from the pool of DNA
      during the library preparation and sequencing steps and that special
      considerations must be taken when aligning hybrid reads to a reference when the
      populations/species are divergent.

PMID- 29329458
TI  - Three Fatty Acyl-Coenzyme A Reductases, BdFAR1, BdFAR2 and BdFAR3, are Involved
      in Cuticular Wax Primary Alcohol Biosynthesis in Brachypodium distachyon.
AB  - Plant cuticular wax is a heterogeneous mixture of very long chain fatty acids
      (VLCFAs) and their derivatives. Primary alcohols are the dominant wax components
      throughout leaf development of Brachypodium distachyon (Brachypodium). However,
      the genes involved in primary alcohol biosynthesis have not been investigated and
      their exact biological function remains unclear in Brachypodium to date. Here, we
      monitored the leaf wax profile and crystal morphology during Brachypodium leaf
      morphogenesis, and isolated three Brachypodium fatty acyl-CoA reductase (FAR)
      genes, named BdFAR1, BdFAR2 and BdFAR3, then analyzed their biochemical
      activities, substrate specificities, expression patterns, subcellular
      localization and stress induction. Transgenic expression of BdFAR genes in yeast
      (Saccharomyces cerevisiae), tomato (Solanum lycopersicum), Arabidopsis
      (Arabidopsis thaliana) and Brachypodium increased the production of primary
      alcohols. The three BdFAR genes were preferentially expressed in Brachypodium
      aerial tissues, consistent with known sites of wax primary alcohol deposition,
      and localized in the endoplasmic reticulum (ER) in Arabidopsis protoplasts.
      Finally, expression of the BdFAR genes was induced by drought, cold and ABA
      treatments, and drought stress significantly increased cuticular wax accumulation
      in Brachypodium. Taken together, these results indicate that the three BdFAR
      genes encode active FARs involved in the biosynthesis of Brachypodium wax primary
      alcohols and respond to abiotic stresses.

PMID- 29329460
TI  - Survey of Parasitic Bacteria in Bat Bugs, Colorado.
AB  - Bat bugs (Cimex adjunctus Barber) (Hemiptera: Cimicidae) collected from big brown
      bats (Eptesicus fuscus Palisot de Beauvoir) in Colorado, United States were
      assessed for the presence of Bartonella, Brucella, and Yersinia spp. using
      molecular techniques. No evidence of Brucella or Yersinia infection was found in
      the 55 specimens collected; however, 4/55 (7.3%) of the specimens were positive
      for Bartonella DNA. Multi-locus characterization of Bartonella DNA shows that
      sequences in bat bugs are phylogenetically related to other Bartonella isolates
      and sequences from European bats.

PMID- 29329461
TI  - High heritability of adolescent sleep-wake behavior on free, but not school days:
      a long-term twin study.
AB  - Adolescence development is characterized by significant changes in sleep biology.
      Despite an overall decline in sleep duration and a delay in bedtime, significant
      interindividual variation in sleep has been reported. The aim of the current
      study was to examine genetic and environmental influences on sleep in adolescence
      using long-term (6 month) actigraphy measurements, differentiating between school
      and free days. Sixteen monozygotic (n = 32) and 10 dizygotic (n = 20) twin pairs
      (mean age 12.8 +/- 1.0 years; 25 females) participated in the study. Structural
      equation modeling was used to compute genetic, shared environmental and unique
      environmental contributors to sleep behavior. We found significantly more genetic
      influence on sleep timing (sleep midpoint; school: 14%, free: 90%) and duration
      (school: 15%; free: 68%) on free compared with school days. On the other hand,
      the genetic influence on measures of sleep quality (sleep efficiency and sleep
      onset latency) was high (>60%) and less dependent on the day of measurement. Only
      wake after sleep onset (WASO) exhibited a strong shared environmental influence
      (> 52%) on both school and free days, suggesting that behavioral/environmental
      interventions may help reduce WASO. In addition, self-reported chronotype was
      also highly genetically influenced (75%). Disrupted, ill-timed, and insufficient
      sleep in adolescence is associated with poor mental and physical health outcomes.
      Our findings of a strong genetic contribution to sleep in adolescence suggest
      that sleep may mark a genetic vulnerability to poor outcomes.

PMID- 29329462
TI  - Silibinin from Silybum marianum Stimulates Embryonic Stem Cell Vascular
      Differentiation via the STAT3/PI3-K/AKT Axis and Nitric Oxide.
AB  - Silibinin, the bioactive compound of milk thistle (Silybum marianum), exerts
      tissue protective and regenerative effects that may include stem cell
      differentiation toward vascular cells. The purpose of the present study was to
      investigate whether silibinin stimulates blood vessel formation from mouse
      embryonic stem (ES) cells and to unravel the underlying signaling cascade.
      Vascular branching points were assessed by confocal laser scanning microscopy and
      computer-assisted image analysis of CD31-positive cell structures. Protein
      expression of vascular markers and activation of protein kinases were determined
      by western blot. Nitric oxide (NO) generation was investigated by use of the
      fluorescent dye 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate.
      Silibinin dose-dependently increased CD31-positive vascular branching points in
      embryoid bodies cultivated from ES cells. This was paralleled by increase of
      protein expression levels for the endothelial-specific markers vascular
      endothelial cadherin (VE-cadherin), vascular endothelial growth factor receptor
      2, and hypoxia-inducible factor-1alpha. Moreover, silibinin increased activation
      of endothelial nitric oxide synthase (eNOS), which boosted generation of NO in
      embryoid bodies and enhanced phosphorylation of signal transducer and activator
      of transcription 3 (STAT3) as well as phosphoinositide 3-kinase (PI3-K) and AKT.
      Vasculogenesis, VE-cadherin expression, STAT3 and AKT phosphorylation, NO
      generation, and eNOS phosphorylation were inhibited by the small molecule STAT3
      inhibitor Stattic, AKT inhibitor VIII, the PI3-K inhibitor LY294002, or the NOS
      inhibitor Nomega-Nitro-L-arginine methyl ester hydrochloride. In conclusion, our
      findings indicate that silibinin induces vasculogenesis of ES cells via
      activation of STAT3, PI3-K, and AKT, which regulate NO generation by eNOS.

PMID- 29329464
TI  - [The Use of Social Networks and Physical Activity Patterns of Adolescents in
      Obesity Therapy - A Sociodemographic Stratified Analysis].
AB  - The improvement of existing obesity treatment for children and adolescents
      requires knowledge about social and personal conditions, individual needs, and
      life style. From particular importance are information about physical activity
      and media use, in order to target and adjust content and methods of therapy
      interventions. In 2013, 510 adolescents aged 11 to 17 years participated in a
      survey on above named factors. Physical activities were conducted with friends
      (64%) and in sport clubs (43%). Girls (OR 0.55) and children of unemployed
      parents (OR 0.28) had reduced chances to participate in sports clubs. Through
      social media social networks, primarily Facebook, were widely used. The use of
      the network functions differed among socio-demographic groups. Participants who
      completed obesity treatments expressed their desire to share their experience
      with other treatment participants (79%) and with the therapy team (37%). The
      results indicate the need for individualised treatment approaches.

PMID- 29329463
TI  - Ginsenoside Rh1: A Systematic Review of Its Pharmacological Properties.
AB  - Ginsenoside Rh1 is one of major bioactive compounds extracted from red ginseng,
      which has been increasingly used for enhancing cognition and physical health
      worldwide. The objective of this study was to review the pharmacological effects
      of ginsenoside Rh1 in a systematic manner. We performed searches on eight
      electronic databases including MEDLINE (Pubmed), Scopus, Google Scholar, POPLINE,
      Global Health Library, Virtual Health Library, the System for Information on Grey
      Literature in Europe, and the New York Academy of Medicine Grey Literature Report
      to select the original research publications reporting the biological and
      pharmacological effects of ginsenoside Rh1 from in vitro and in vivo studies
      regardless of publication language and study design. Upon applying the inclusion
      and exclusion criteria, we included a total of 57 studies for our systemic
      review. Ginsenoside Rh1 exhibited the potent characteristics of anti
      inflammatory, antioxidant, immunomodulatory effects, and positive effects on the
      nervous system. The cytotoxic effects of ginsenoside Rh1 were dependent on
      different types of cell lines. Other pharmacological effects including
      estrogenic, enzymatic, anti-microorganism activities, and cardiovascular effects
      have been mentioned, but the results were considerably diverged. A higher quality
      of evidence on clinical trial studies is highly recommended to confirm the
      consistent efficacy of ginsenoside Rh1.

PMID- 29329466
TI  - Association Between Body Weight Change Before and After Delivery and Development
      of Nonmetabolic Syndrome: A Prospective Study.
AB  - The aim of the work was to investigate the association between body weight change
      before and after delivery and development of nonmetabolic syndrome in Chinese
      females aged >=40 years. We selected 789 participants without metabolic syndrome
      randomly from a baseline survey performed in Luzhou, China in 2011. We took the
      group with decreasing or no increasing body mass index difference during a
      pregnancy as "R-Body Mass Index 1" (n=286) and divided the group with increasing
      body mass index difference during a pregnancy into "R-Body Mass Index 2" (n=254)
      and "R-Body Mass Index 3" (n=249) based upon P50. All study participants were
      followed up every year, and a questionnaire, physical examination, and
      biochemical detection were administered after 3 years. Of 789 participants, 82
      nonmetabolic syndrome women developed metabolic syndrome during 3-year follow-up.
      The morbidity of metabolic syndrome in the R-BMI1, R-BMI2, and R-BMI3 groups was
      5.2%, 11.8%, and 14.9%, respectively. Compared to the R-BMI1 group, the relative
      risk for R-BMI2 was 1.92 (95% confidence interval: 1.03-3.58, p=0.040) and for R
      BMI3 was 2.20 (95% confidence interval: 1.20-4.03, p=0.011). After adjusting for
      age, BMI, WHR, baseline blood glucose, HbA1c, TG, HDL-C, SBP, DBP, age of
      menarche and menopause, and delivery times, the relative risks were similar to
      the unadjusted relative risks. In conclusion, body weight change after delivery
      was associated with metabolic syndrome: the higher the weight gain, the higher
      the risk of metabolic syndrome.

PMID- 29329468
TI  - Closure of an Intraoperatively Enlarged Macular Hole by Revision Surgery with
      Free ILM Flaps.

PMID- 29329467
TI  - Low Aromatase Activity and Estradiol/Sex Hormone Binding Globulin Ratio are
      Associated with Total Hip Bone Mineral Density and the Presence of Osteoporosis:
      A Study in Chinese Postmenopausal Women.
AB  - Several groups have reported the important role of estradiol (E2) and
      testosterone (T) in postmenopausal osteoporosis (PMOP). Because aromatase
      catalyzes the conversion of T to E2, the purpose of this study was to determine
      the influence of aromatase activity on the bone mineral density (BMD) in
      postmenopausal women. A total of 344 postmenopausal women were selected for this
      study. Serum E2, T, sex hormone-binding globulin (SHBG), calcium (Ca), alkaline
      phosphatase (ALP), C-terminal telopeptide of type I collagen (CTX), and
      procollagen type I amino-terminal propeptide (PINP) were examined. The E2/T was
      positively associated with total hip BMD and PINP (p<0.05). When E2/T was divided
      into quartiles, participants in lower quartiles of E2/T were likely to have
      higher PINP and lower BMD (p<0.05). The prevalence of osteoporosis significantly
      increased as E2/T ratio decreased. The receiver operating characteristic (ROC)
      curves were constructed for serum E2, free E2 index (FEI), and E2/T, to assess
      their diagnostic accuracy in PMOP. The overall area under the curve (AUC) were
      0.83 (95% CI=0.77-0.88) for E2, 0.87 (95% CI=0.82-0.92) for FEI, and 0.89 (95%
      CI=0.85-0.94), respectively. In conclusion, the study suggests that in
      postmenopausal women, aromatase activity could be an important determinant of
      skeletal health. The women with lower aromatase activity may have greater
      likelihood of PMOP and the E2/T was expected to be a valuable indicator for the
      prediction of PMOP and to monitor the process of osteoporosis.

PMID- 29329469
TI  - Pigment Dispersion Syndrome Mimicking Congenital Horner Syndrome.

PMID- 29329470
TI  - [The Epidemiology of Pressure Ulcer in Germany: Systematic Review].
AB  - BACKROUND: Pressure ulcers are considered as indicators of the quality of care.
      The aim of this study was to provide a systematic review of the incidence and
      prevalence of pressure ulcers in Germany between 2010 and 2015. METHODS: The
      databases PubMed, CINAHL, DIMDI, Web of Science, LIVIVO, Google, Google Scholar,
      as well as the publishers Springer and the Thieme were searched until the end of
      February 2016. The extracted data were monitored by two reviewers. A risk of bias
      assessment was conducted. RESULTS: 219 epidemiologic figures were found in 67
      studies and documents. Most data were identified for the hospital setting. The
      majority of figures in long-term care was based on primary research. Considering
      sources of high methodological quality, prevalence in long-term care varied
      between 2% and 5% and between 2% to 4% in hospitals (category 2 and above).
      Routine data collections showed heterogeneous results from the hospital settings
      with prevalence from 0.07% to 4.37%. No incidence figures and no routine data
      collections were identified for ambulatory settings. Prevalence varied between 2
      and 4% (including category 1). CONCLUSION: Review results indicate that pressure
      ulcers are frequent within all health care settings in Germany. Disregarding
      methodological limitations, pressure ulcer prevalence is between 2% and 5% in
      long-term care patients. Due to the heterogeneity of the available data,
      generalizable statements are not possible for the hospital settings. Pressure
      ulcer prevalence is most likely at least 2%. Results indicate that pressure ulcer
      preventive measures need to be improved in Germany.

PMID- 29329471
TI  - Diagnosing Meniscal Pathology and Understanding How to Evaluate a Postoperative
      Meniscus Based on the Operative Procedure.
AB  - Magnetic resonance imaging (MRI) represents the preferred noninvasive imaging
      technique to diagnose meniscal pathology in the pre- and postoperative setting.
      Furthermore, characterization of meniscal tissue MR properties has been possible
      by the development of advanced MRI techniques. Suspected meniscal tears are a
      frequent indication for MRI and the International Society of Arthroscopy, Knee
      Surgery and Orthopaedic Sports Medicine (ISAKOS) classification system has been
      developed to facilitate accurate and uniform reporting of such meniscal tears.
      Partial meniscectomy and meniscal suture repair are among the commonly performed
      procedures and several signs have been described to detect postoperative
      recurrent tears on MRI. Other techniques that have proven useful for meniscal
      assessment are ultrasound (US) and computed tomography (CT) arthrography. In
      recent years, US is being increasingly used in the selective assessment of some
      meniscal pathology such as tears, parameniscal cysts and meniscal extrusion as it
      is a relatively inexpensive, accessible, and safe technique. CT arthrography has
      been advocated as an acceptable alternative in patients with contraindications
      for MRI, with comparable diagnostic performance.

PMID- 29329473
TI  - Intrabiliary argon plasma coagulation hemostasis by direct cholangioscopy for a
      tricky post-ERCP bleeding.

PMID- 29329472
TI  - Impact of Thrombus Sidedness on Presentation and Outcomes of Patients with
      Proximal Lower Extremity Deep Vein Thrombosis.
AB  - Small studies have suggested differences in demographics and outcomes between
      left- and right-sided deep vein thrombosis (DVT), and also unilateral versus
      bilateral DVT. We investigated the clinical presentation and outcomes of patients
      with DVT based on thrombus sidedness. The authors used the data from the Registro
      Informatizado Enfermedad TromboEmbolica (RIETE) database (2001-2016) to identify
      patients with symptomatic proximal lower-extremity DVT. Main outcomes included
      cumulative 90-day symptomatic pulmonary embolism (PE) and 1-year mortality.
      Overall, 30,445 patients were included. The majority of DVTs occurred in the left
      leg (16,421 left-sided, 12,643 right-sided, and 1,390 bilateral; p < 0.001 for
      chi-squared test comparing all three groups). Comorbidities were relatively
      similar in those with left-sided and right-sided DVT. Compared with those with
      left-sided DVT, patients with right-sided DVT had higher relative frequency of PE
      (26% versus 23%, p < 0.001) and 1-year mortality (odds ratio [OR]: 1.08; 95%
      confidence interval [CI]: 1.00-1.18). This difference in mortality did not
      persist after multivariable adjustment (OR: 1.01; 95% CI: 0.93-1.1). Patients
      with bilateral DVT had a greater burden of comorbidities such as heart failure,
      and recent surgery compared with those with unilateral DVT (p < 0.001), and
      higher relative frequency of PE (48%), and 1-year mortality (24.1%). Worse
      outcomes in patients with bilateral DVT were attenuated but persisted after
      multivariable adjustment for demographics and risk factors (OR: 1.64; 95% CI:
      1.43-1.87). Patients with bilateral DVT had worse outcomes during and after
      discontinuation of anticoagulation. There is a left-sided preponderance for
      proximal lower-extremity DVT. Compared with those with left-sided DVT, patients
      with right-sided DVT have slightly higher rates of PE. Bilateral DVT is
      associated with markedly worse short-term and 1-year outcomes.

PMID- 29329474
TI  - Immediate retrieval of a maldeployed lumen-apposing metal stent from a walled-off
      cavity.

PMID- 29329476
TI  - Pay attention to a "window-blind" appearance of the distal rectal muscle layer
      during endoscopic submucosal dissection.

PMID- 29329475
TI  - Endoscopic ultrasound-guided sclerosant injection and coil embolization of
      bleeding gastric varices.

PMID- 29329477
TI  - Colorectal endoscopic submucosal dissection using the "dental floss with rubber
      band method".

PMID- 29329478
TI  - Migrated endoclip removal after cholecystectomy under digital single-operator
      cholangioscopy guidance.

PMID- 29329479
TI  - Individual endoscopic management of anastomotic insufficiency after esophagectomy
      for esophageal squamous cell carcinoma and creation of a neostomach.

PMID- 29329480
TI  - Direct endoscopy and diagnosis of adenocarcinoma following metal stent-based
      drainage of a pancreatic cyst.

PMID- 29329481
TI  - Antibiotics Development and the Emergence of Resistance: Clinical Pharmacology to
      the Rescue.

PMID- 29329483
TI  - Recognizing elevated blood pressure in pediatrics: the value of repeated
      measures.

PMID- 29329482
TI  - Pharmacokinetics of Rolapitant in Patients With Mild to Moderate Hepatic
      Impairment.
AB  - Rolapitant is a selective and long-acting neurokinin-1 receptor antagonist
      approved in an oral formulation in combination with other antiemetic agents for
      the prevention of delayed chemotherapy-induced nausea and vomiting in adults.
      This was a phase 1 open-label, parallel-group pharmacokinetic and safety study of
      a single oral dose of 180 mg of rolapitant and its major active metabolite, M19,
      in subjects with mild and moderate hepatic impairment compared with healthy
      matched controls. Pharmacokinetics were assessed by a mixed-model analysis of
      variance of log-transformed values for maximum observed plasma concentration
      (Cmax ), observed time at Cmax (tmax ), area under the plasma concentration-time
      curve (AUC) from time 0 to the time of the last quantifiable concentration (AUC0
      t ), and AUC from time 0 to 120 hours (AUC0-120 ), with hepatic group as a fixed
      effect. Mean rolapitant Cmax , AUC0-t , and AUC0-120 were similar in the mild
      hepatic impairment and healthy control groups. In subjects with moderate hepatic
      impairment, AUC0-t was similar and Cmax was 25% lower than in healthy controls.
      Mean M19 Cmax and AUC0-t were similar in the mild hepatic impairment group and
      healthy controls, but <20% lower in those with moderate hepatic impairment versus
      healthy controls. Fraction of unbound rolapitant was comparable in all groups for
      rolapitant and M19. Rolapitant was well tolerated in all groups, without serious
      adverse events. Pharmacokinetic differences between healthy subjects and those
      with mild or moderate hepatic impairment are unlikely to pose a safety risk and
      do not warrant predefined dosage adjustment in the presence of hepatic
      impairment.

PMID- 29329484
TI  - Effects of Teriparatide Compared with Risedronate on the Risk of Fractures in
      Subgroups of Postmenopausal Women with Severe Osteoporosis: The VERO Trial.
AB  - The 2-year, randomized, double-blind, active-controlled fracture endpoint VERO
      study included postmenopausal women with established osteoporosis, who had at
      least 2 moderate or 1 severe baseline vertebral fractures (VFx), and bone mineral
      density (BMD) T-score <=-1.5. Patients were treated with either s.c. daily
      teriparatide 20 MUg or oral weekly risedronate 35 mg. As previously reported, the
      risk of new VFx and clinical fractures (a composite of clinical VFx and
      nonvertebral fragility fractures [NVFFx]) was statistically significantly reduced
      with teriparatide compared with risedronate. Here we present the prospectively
      planned subgroup analyses of fracture data across subgroups, which were
      predefined by the following baseline characteristics: age, number and severity of
      prevalent VFx, prevalent nonvertebral fractures (NVFx), glucocorticoid use, prior
      osteoporosis drugs, recent bisphosphonate use, clinical VFx in the year before
      study entry, and baseline BMD. Heterogeneity of the treatment effect on the
      primary endpoint (new VFx), and the four key secondary endpoints (including
      clinical fractures and NVFFx) were investigated by logistic and Cox proportional
      hazards regression models. A total of 1360 women were randomized and treated (680
      per group). Mean age was 72.1 years, mean (SD) number of prevalent VFx was 2.7
      (2.1), 55.4% had a BMD T-score <-2.5, 36.5% had a recent clinical VFx, 28.3% had
      a prior major NVFx, 43.2% were osteoporosis drug-naive, 39.3% were recent
      bisphosphonate users, and 9.3% were taking glucocorticoids at a prednisone
      equivalent dose of >5 mg/d. For most fracture endpoints, the risk reduction of
      teriparatide versus risedronate did not significantly differ in any of the
      subgroups analyzed (treatment-by-subgroup interaction p > 0.1), with most
      subgroups mirroring results from the total study population. In conclusion, in
      postmenopausal women with severe osteoporosis, the antifracture efficacy of
      teriparatide compared with risedronate was consistent in a wide range of patient
      settings, including treatment-naive and previously treated patients. (c) 2018 The
      Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.

PMID- 29329485
TI  - Photo-Initiated Reduction of CO2 by H2 on Silica Surface.
AB  - The reduction of CO2 is a promising route to produce valuable chemicals or fuels
      and create C-neutral resource cycles. Many different approaches to CO2 reduction
      have been investigated, but the ability of vacuum UV (VUV) irradiation to cleave
      C-O bonds has remained largely unexplored for use in processes that convert CO2
      into useful products. Compared with other photo-driven CO2 conversion processes,
      VUV-initiated CO2 reduction can achieve much greater conversion under common
      photochemical reaction conditions when H2 and non-reducible oxides are present.
      Infrared spectroscopy provides evidence for a chain reaction initiated by VUV
      induced CO2 splitting, which is enhanced in the presence of H2 and silica. When
      the reaction is carried out in the presence of silica or alumina surfaces, CO
      yields are increased and CH4 is formed as the only other detected product. CH4
      production is not promoted by traditional photocatalysts such as TiO2 under these
      conditions. Assuming improvements in lamp and reactor efficiencies with scale up,
      or coupling with other available CO/CO2 hydrogenation techniques, these results
      reveal a potential, simple strategy by which CO2 could be valorized.

PMID- 29329487
TI  - A History of Pivotal Advances in Clinical Research into Bone and Mineral
      Diseases.

PMID- 29329486
TI  - Cost effectiveness of guided Internet-based interventions for depression in
      comparison with control conditions: An individual-participant data meta-analysis.
AB  - BACKGROUND: There is limited evidence on the cost effectiveness of Internet-based
      treatments for depression. The aim was to evaluate the cost effectiveness of
      guided Internet-based interventions for depression compared to controls. METHODS:
      Individual-participant data from five randomized controlled trials (RCT),
      including 1,426 participants, were combined. Cost-effectiveness analyses were
      conducted at 8 weeks, 6 months, and 12 months follow-up. RESULTS: The guided
      Internet-based interventions were more costly than the controls, but not
      statistically significant (12 months mean difference = ?406, 95% CI: - 611 to
      1,444). The mean differences in clinical effects were not statistically
      significant (12 months mean difference = 1.75, 95% CI: - .09 to 3.60 in Center
      for Epidemiologic Studies Depression Scale [CES-D] score, .06, 95% CI: - .02 to
      .13 in response rate, and .00, 95% CI: - .03 to .03 in quality-adjusted life
      years [QALYs]). Cost-effectiveness acceptability curves indicated that high
      investments are needed to reach an acceptable probability that the intervention
      is cost effective compared to control for CES-D and response to treatment (e.g.,
      at 12-month follow-up the probability of being cost effective was .95 at a
      ceiling ratio of 2,000 ?/point of improvement in CES-D score). For QALYs, the
      intervention's probability of being cost effective compared to control was low at
      the commonly accepted willingness-to-pay threshold (e.g., at 12-month follow-up
      the probability was .29 and. 31 at a ceiling ratio of 24,000 and 35,000 ?/QALY,
      respectively). CONCLUSIONS: Based on the present findings, guided Internet-based
      interventions for depression are not considered cost effective compared to
      controls. However, only a minority of RCTs investigating the clinical
      effectiveness of guided Internet-based interventions also assessed cost
      effectiveness and were included in this individual-participant data meta
      analysis.

PMID- 29329488
TI  - Genetic and Molecular Insights Into Genotype-Phenotype Relationships in
      Osteopathia Striata With Cranial Sclerosis (OSCS) Through the Analysis of Novel
      Mouse Wtx Mutant Alleles.
AB  - The X-linked WTX/AMER1 protein constitutes an important component of the beta
      catenin destruction complex that can both enhance and suppress canonical beta
      catenin signaling. Somatic mutations in WTX/AMER1 have been found in a proportion
      of the pediatric kidney cancer Wilms' tumor. By contrast, germline mutations
      cause the severe sclerosing bone dysplasia osteopathia striata congenita with
      cranial sclerosis (OSCS), a condition usually associated with fetal or perinatal
      lethality in male patients. Here we address the developmental and molecular
      function of WTX by generating two novel mouse alleles. We show that in addition
      to the previously reported skeletal abnormalities, loss of Wtx causes severe
      midline fusion defects including cleft palate and ectopic synostosis at the base
      of the skull. By contrast, deletion of the C-terminal part of the protein results
      in only mild developmental abnormalities permitting survival beyond birth. Adult
      analysis, however, revealed skeletal defects including changed skull morphology
      and an increased whole-body bone density, resembling a subgroup of male patients
      carrying a milder, survivable phenotype. Molecular analysis in vitro showed that
      while beta-catenin fails to co-immunoprecipitate with the truncated protein,
      partial recruitment appears to be achieved in an indirect manner using AXIN/AXIN2
      as a molecular bridge. Taken together our analysis provides a novel model for WTX
      caused bone diseases and explains on the molecular level how truncation mutations
      in this gene may retain some of WTX-protein functions. (c) 2018 American Society
      for Bone and Mineral Research.

PMID- 29329489
TI  - Mycophenolic Acid and Its Metabolites in Kidney Transplant Recipients: A
      Semimechanistic Enterohepatic Circulation Model to Improve Estimating Exposure.
AB  - Mycophenolic acid (MPA) is an approved immunosuppressive agent widely prescribed
      to prevent rejection after kidney transplantation. Wide between-subject
      variability (BSV) in MPA exposure exists which in part may be due to variability
      in enterohepatic recirculation (EHC). Several modeling strategies were developed
      to evaluate EHC as part of MPA pharmacokinetics, however mechanistic
      representation of EHC is limited. These models have not provided a satisfactory
      representation of the physiology of EHC in their modeling assumptions. The aim of
      this study was i) to develop an integrated model of MPA (total and unbound) and
      its metabolites (MPAG and acyl-MPAG) in kidney recipients, where this model
      provides a more physiological representation of EHC process, and ii) to evaluate
      the effect of donor and recipient clinical covariates and genotypes on MPA
      disposition. A five-compartment model with first-order input into an unbound MPA
      compartment connected to the MPAG, acyl-MPAG, and gallbladder compartment best
      fit the data. To represent the EHC process, the model was built based on the
      physiological concepts related to the hepatobiliary system and the gallbladder
      filling and emptying processes. The effect of cyclosporine versus tacrolimus on
      clearance of unbound MPA was included in the base model. Covariate analysis
      showed creatinine clearance to be significant on oral clearance of unbound MPA.
      The hepatic nuclear factor 1 alpha (HNF1A) genetic single nucleotide polymorphism
      (SNP) (rs2393791) in the recipient significantly affected the fraction of
      enterohepatically-circulated drug. Oral clearance of MPAG was affected by
      recipient IMPDH1 SNP (rs2288553), diabetes at the time of transplant, and donor
      sex.

PMID- 29329490
TI  - Nematode eggs observed in cytology of cerebrospinal fluid diagnostic for
      intramedullary Spirocerca lupi spinal cord migration.
AB  - Spinal spirocercosis due to aberrant Spirocerca lupi nematode migration is an
      emerging etiology for acute myelitis in dogs in Israel, causing severe, mostly
      nonsymmetrical hind limb paresis or paralysis, and sometimes tetraparesis or
      tetraparalysis. So far, incidental identification of parasites during spinal
      surgery or at necropsy provides the only definite diagnosis, while antemortem
      diagnosis of this condition has been uncertain. Specifically, antemortem
      diagnosis is based on the typical clinical presentation of acute, progressive,
      asymmetrical hind limb paresis or paralysis, with moderate to severe eosinophilic
      to mixed cerebrospinal fluid (CSF) pleocytosis and increased CSF protein
      concentration. Exclusion of other differential diagnoses also requires using
      spinal cord imaging. In this novel report, we document a case of an intradural
      spinal spirocercosis in a dog, diagnosed antemortem, by detecting S lupi eggs in
      the CSF, and subsequent treatment, resulting in the resolution of the clinical
      signs.

PMID- 29329492
TI  - Failure to confirm high blood pressures in pediatric care-quantifying the risks
      of misclassification.
AB  - Pediatric practice guidelines call for repeating an elevated office blood
      pressure (BP) at the same visit, but there are few data available to support this
      recommendation. We compared the visit results in children aged 3 to 17 years with
      a BP reading >=95th percentile (n = 186 732) based on the initial BP and the mean
      of two BP readings, using electronic medical records from 2012-2015. Failure to
      repeat an initial BP reading >=95th percentile would lead to a false
      "hypertensive" visit result in 54.1% of children who would require follow-up
      visits. After an initial visit result indicating hypertension, hypertension stage
      I or stage II was sustained in 2.3% and 11.3% of youth during their next visits,
      respectively. In conclusion, only approximately half of the pediatric patients
      would be correctly classified based on their initial BP. The recommendation to
      repeat high BP during the same visit needs to be emphasized because it saves
      unnecessary follow-up visits.

PMID- 29329493
TI  - A Randomized Double-Blind Controlled Trial of Intravenous Meloxicam in the
      Treatment of Pain Following Dental Impaction Surgery.
AB  - : This randomized, controlled phase 2 study was conducted to evaluate the
      analgesic efficacy, safety, and tolerability of single intravenous (IV) doses of
      15 mg, 30 mg, and 60 mg meloxicam compared with oral ibuprofen 400 mg and placebo
      after dental impaction surgery. The primary efficacy end point was the sum of
      time-weighted pain intensity differences for 0-24 hours postdose. Among 230
      evaluable subjects, meloxicam IV 60 mg produced the greatest reduction in pain,
      followed by the 30-mg and 15-mg doses. Statistically significant differences in
      summed pain intensity differences over 24 hours were demonstrated for each active
      treatment group vs placebo (favoring active treatment) and for meloxicam IV 30 mg
      and 60 mg vs ibuprofen 400 mg (favoring meloxicam IV). Moreover, there was a
      statistically significant dose response for meloxicam IV 15 mg to 60 mg. The
      onset of action for meloxicam IV was rapid and sustained; significant differences
      in pain intensity differences were detected as early as 10 minutes postdose and
      lasted through the 24-hour postdose period. Subjects in the meloxicam IV groups
      were more likely than placebo recipients to achieve perceptible and meaningful
      pain relief and were less likely to use rescue medication. Patient-reported
      global evaluation showed that meloxicam IV 60 mg had the highest rating. There
      were no deaths, serious adverse events, or discontinuations due to adverse
      events. The incidence of subjects with >=1 treatment-emergent adverse event was
      greatest in the placebo group, followed by the groups that received ibuprofen,
      meloxicam IV 15 mg, 30 mg, and 60 mg. Nausea was the most commonly reported
      treatment-emergent adverse event. CLINICAL TRIAL REGISTRATION NUMBER:
      NCT00945763.

PMID- 29329494
TI  - Contraceptive Use over Five Years After Receipt Or Denial of Abortion Services.
AB  - CONTEXT: Nonuse and inconsistent use of contraceptives contribute to a high
      incidence of unintended pregnancy and abortion among U.S. women. Little is known,
      however, about how these outcomes shape women's subsequent contraceptive use and
      unintended pregnancy risk. METHODS: Contraceptive use was examined among 880
      participants in the Turnaway Study, a five-year longitudinal study of women who
      sought abortions at 30 U.S. facilities in 2008-2010. Multivariable mixed-effects
      logistic and multinomial regression models assessed differences in use by whether
      women received the abortion; results were used to calculate predicted percentages
      of women using each method. The main groups of interest were 415 women who had an
      abortion at a gestation near their facility's limit and 160 who were denied
      abortion because they were beyond the limit, and who consequently gave birth.
      RESULTS: During each of the approximately five years of follow-up, the predicted
      percentage using any contraceptive method was 86% among women who had the
      abortion and 81% among those denied it. Over the entire period, the former women
      were more likely than the latter to use any method (odds ratio, 1.8). However,
      they were less likely to rely on female sterilization, rather than no method
      (risk ratio, 0.5), and more likely to use barrier methods (1.7) or short-acting
      reversible contraceptives (2.6). CONCLUSION: Women's elevated risk of unintended
      pregnancy after abortion is likely due at least partly to reliance on methods
      with relatively low effectiveness. Factors affecting contraceptive access
      postabortion, as well as individual characteristics such as fecundability,
      require research attention.

PMID- 29329495
TI  - Organometallic-Mediated Radical Polymerization of Vinylidene Fluoride.
AB  - An unprecedented level of control for the radical polymerization of vinylidene
      fluoride (VDF), yielding well-defined PVDF (at least up to 14 500 g mol-1 ) with
      low dispersity (<=1.32), was achieved using organometallic-mediated radical
      polymerization (OMRP) with an organocobalt compound as initiator. The high chain
      end fidelity was demonstrated by the synthesis of PVDF- and PVAc-containing di
      and triblock copolymers. DFT calculations rationalize the efficient reactivation
      of both head and tail chain end dormant species.

PMID- 29329496
TI  - Positive-Feedback Regulation of Subchondral H-Type Vessel Formation by
      Chondrocyte Promotes Osteoarthritis Development in Mice.
AB  - Vascular-invasion-mediated interactions between activated articular chondrocytes
      and subchondral bone are essential for osteoarthritis (OA) development. Here, we
      determined the role of nutrient sensing mechanistic target of rapamycin complex 1
      (mTORC1) signaling in the crosstalk across the bone cartilage interface and its
      regulatory mechanisms. Then mice with chondrocyte-specific mTORC1 activation
      (Tsc1 CKO and Tsc1 CKOER ) or inhibition (Raptor CKOER ) and their littermate
      controls were subjected to OA induced by destabilization of the medial meniscus
      (DMM) or not. DMM or Tsc1 CKO mice were treated with bevacizumab, a vascular
      endothelial growth factor (VEGF)-A antibody that blocks angiogenesis. Articular
      cartilage degeneration was evaluated using the Osteoarthritis Research Society
      International score. Immunostaining and Western blotting were conducted to detect
      H-type vessels and protein levels in mice. Primary chondrocytes from mutant mice
      and ADTC5 cells were treated with interleukin-1beta to investigate the role of
      chondrocyte mTORC1 in VEGF-A secretion and in vitro vascular formation. Clearly,
      H-type vessels were increased in subchondral bone in DMM-induced OA and aged
      mice. Cartilage mTORC1 activation stimulated VEGF-A production in articular
      chondrocyte and H-type vessel formation in subchondral bone. Chondrocyte mTORC1
      promoted OA partially through formation of VEGF-A-stimulated subchondral H-type
      vessels. In particular, vascular-derived nutrients activated chondrocyte mTORC1,
      and stimulated chondrocyte activation and production of VEGF, resulting in
      further angiogenesis in subchondral bone. Thus a positive-feedback regulation of
      H-type vessel formation in subchondral bone by articular chondrocyte nutrient
      sensing mTORC1 signaling is essential for the pathogenesis and progression of OA.
      (c) 2018 American Society for Bone and Mineral Research.

PMID- 29329497
TI  - Pharmacokinetic Interactions Between Elbasvir/Grazoprevir and Immunosuppressant
      Drugs in Healthy Volunteers.
AB  - Elbasvir (EBR)/grazoprevir (GZR) may be coadministered with immunosuppressant
      drugs in posttransplant people who are infected with hepatitis C virus. The aim
      of the present study was to assess the safety and pharmacokinetic interactions
      between EBR and GZR and single doses of cyclosporine, tacrolimus, mycophenolate
      mofetil (MMF), and prednisone. This was a 4-part, open-label study in 58 healthy
      volunteers. Participants received single doses of cyclosporine 400 mg, tacrolimus
      2 mg, MMF 1 g, or prednisone 40 mg alone or in the presence of once-daily EBR 50
      mg/GZR 200 mg. Multiple oral doses of EBR + GZR had no significant effect on
      cyclosporine. However, in the presence of cyclosporine, the 24-hour area under
      the concentration-time curve of GZR was increased by approximately 15-fold
      (geometric mean ratio [90%CI] 15.21 [12.83; 18.04]); the concentration of EBR was
      increased approximately 2-fold in the presence of cyclosporine. Coadministration
      of EBR/GZR and tacrolimus did not affect the pharmacokinetics of EBR or GZR, but
      resulted in an increase in tacrolimus AUC (geometric mean ratio [90%CI] 1.43
      [1.24; 1.64]). There were no clinically relevant interactions between EBR/GZR and
      either MMF or prednisone. Data from the present study indicate that EBR/GZR may
      be coadministered in people receiving tacrolimus, MMF, and prednisolone. EBR/GZR
      is contraindicated in people receiving cyclosporine because the significantly
      higher concentrations of GZR may increase the risk of transaminase elevations.

PMID- 29329498
TI  - Treatment outcomes of acute bipolar depressive episode with psychosis.
AB  - BACKGROUND: The impact of psychosis on the treatment of bipolar depression is
      remarkably understudied. The primary aim of this study was to compare treatment
      outcomes of bipolar depressed individuals with and without psychosis. The
      secondary aim was to compare the effect of lithium and quetiapine, each with
      adjunctive personalized treatments (APTs), in the psychotic subgroup. METHODS: We
      assessed participants with DSM-IV bipolar depression included in a comparative
      effectiveness study of lithium and quetiapine with APTs (the Bipolar CHOICE
      study). Severity was assessed by the Bipolar Inventory of Symptoms Scale (BISS)
      and by the Clinical Global Impression Scale-Severity-Bipolar Version (CGI-S-BP).
      Mixed models were used to assess the course of symptom change, and Cox regression
      survival analysis was used to assess the time to remission. RESULTS: Psychotic
      features were present in 10.6% (n = 32) of the depressed participants (n = 303).
      Those with psychotic features had higher scores on the BISS before (75.2 +/- 17.6
      vs. 54.9 +/- 16.3; P < .001) and after (37.2 +/- 19.7 vs. 26.3 +/- 18.0; P =
      .003) 6-month treatment. The CGI-S-BP yielded similar results. Participants with
      and without psychosis had similar course of symptom improvement and similar time
      to remission. There was no significant difference in the treatment outcomes of
      lithium (n = 11) and quetiapine (n = 21) among the psychotic subgroup.
      CONCLUSION: Bipolar depressive episodes with psychotic features are more severe,
      and compared to nonpsychotic depressions, present a similar course of
      improvement. Given the small number of participants presenting psychosis, the
      lack of statistically significant difference between lithium- and quetiapine
      based treatment of psychotic bipolar depressive episodes needs replication in a
      larger sample.

PMID- 29329499
TI  - A pilot study of the comparative efficacy of 100 Hz magnetic seizure therapy and
      electroconvulsive therapy in persistent depression.
AB  - BACKGROUND: Magnetic seizure therapy (MST) is a novel brain stimulation technique
      that uses a high-powered transcranial magnetic stimulation device to produce
      therapeutic seizures. Preliminary MST studies have found antidepressant effects
      in the absence of cognitive side effects but its efficacy compared to
      electroconvulsive therapy (ECT) remains unclear. The aim of this study was to
      investigate the therapeutic efficacy and cognitive profile of MST compared to
      standard right unilateral ECT treatment. METHODS: Thirty-seven patients completed
      a course of at least nine ECT or MST treatments in a randomized double-blind
      protocol. Assessments of depression severity and cognition were performed before
      and after treatment. RESULTS: No difference in the antidepressant effectiveness
      between the treatments was seen across any of the clinical outcome measures,
      although the overall response rates in both groups were quite low. In regards to
      cognition, following MST there were significant improvements in tests of
      psychomotor speed, verbal memory, and cognitive inhibition, with no reductions in
      cognitive performance. Following ECT there was significant improvement in only
      one of the cognitive inhibition tasks. With respect to the between-group
      comparisons, the MST group showed a significantly greater improvement on
      psychomotor speed than ECT. CONCLUSIONS: MST showed similar efficacy to right
      unilateral ECT in patients with treatment-resistant depression without cognitive
      side effects but in a sample that was only of sufficient size to demonstrate
      relatively large differences in response between the two groups. Future research
      should aim to optimize the methods of MST administration and compare its efficacy
      to ECT in large randomized controlled trials.

PMID- 29329500
TI  - A C=O???Isothiouronium Interaction Dictates Enantiodiscrimination in Acylative
      Kinetic Resolutions of Tertiary Heterocyclic Alcohols.
AB  - A combination of experimental and computational studies have identified a
      C=O???isothiouronium interaction as key to efficient enantiodiscrimination in the
      kinetic resolution of tertiary heterocyclic alcohols bearing up to three
      potential recognition motifs at the stereogenic tertiary carbinol center. This
      discrimination was exploited in the isothiourea-catalyzed acylative kinetic
      resolution of tertiary heterocyclic alcohols (38 examples, s factors up to >200).
      The reaction proceeds at low catalyst loadings (generally 1 mol %) with either
      isobutyric or acetic anhydride as the acylating agent under mild conditions.

PMID- 29329502
TI  - Energetic Costs, Precision, and Transport Efficiency of Molecular Motors.
AB  - An efficient molecular motor would deliver cargo to the target site at a high
      speed and in a punctual manner while consuming a minimal amount of energy.
      According to a recently formulated thermodynamic principle, referred to as the
      thermodynamic uncertainty relation, the travel distance of a motor and its
      variance are, however, constrained by the free energy being consumed. Here we use
      the principle underlying the uncertainty relation to quantify the transport
      efficiency of molecular motors for varying ATP concentration ([ATP]) and applied
      load (f). Our analyses of experimental data find that transport efficiencies of
      the motors studied here are semioptimized under the cellular condition. The
      efficiency is significantly deteriorated for a kinesin-1 mutant that has a longer
      neck-linker, which underscores the importance of molecular structure. It is
      remarkable to recognize that, among many possible directions for optimization,
      biological motors have evolved to optimize the transport efficiency in
      particular.

PMID- 29329503
TI  - Chemical imaging of aggressive basal cell carcinoma using time-of-flight
      secondary ion mass spectrometry.
AB  - A set of basal cell carcinoma samples, removed by Mohs micrographic surgery and
      pathologically identified as having an aggressive subtype, have been analyzed
      using time-of-flight secondary ion mass spectrometry (SIMS). The SIMS analysis
      employed a gas cluster ion beam (GCIB) to increase the sensitivity of the
      technique for the detection of intact lipid species. The GCIB also allowed these
      intact molecular signals to be maintained while surface contamination and
      delocalized chemicals were removed from the upper tissue surface. Distinct mass
      spectral signals were detected from different regions of the tissue (epidermis,
      dermis, hair follicles, sebaceous glands, scar tissue, and cancerous tissue)
      allowing mass spectral pathology to be performed. The cancerous regions of the
      tissue showed a particular increase in sphingomyelin signals that were detected
      in both positive and negative ion mode along with increased specific
      phosphatidylserine and phosphatidylinositol signals observed in negative ion
      mode. Samples containing mixed more and less aggressive tumor regions showed
      increased phosphatidylcholine lipid content in the less aggressive areas similar
      to a punch biopsy sample of a nonaggressive nodular lesion.

PMID- 29329504
TI  - Expression of vitamin D receptor in the subsynovial connective tissue in women
      with carpal tunnel syndrome.
AB  - : Studies suggest that low vitamin D levels are associated with carpal tunnel
      syndrome. We aimed to evaluate whether level of vitamin D receptor expression in
      the endothelial cells of the subsynovial connective tissue is associated with
      clinical features of carpal tunnel syndrome. We obtained the subsynovial
      connective tissue from 52 women with carpal tunnel syndrome during surgery and
      performed immunohistochemical analysis of vitamin D receptors in the endothelial
      cells of the subsynovial connective tissue. We explored correlation of vitamin D
      receptor expression with clinical features of carpal tunnel syndrome, such as
      age, symptom duration, symptom severity and electrophysiological severity.
      Diverse range of vitamin D receptor expression was observed. Vitamin D receptor
      expression was independently associated with distal motor latency. This suggests
      that vitamin D receptor expression may be associated with disease progression, as
      prolonged distal motor latency reflects severity of the disease. Further studies
      are necessary to explore the role of vitamin D and vitamin D receptors in
      patients with carpal tunnel syndrome. LEVEL OF EVIDENCE: IV.

PMID- 29329501
TI  - Sustained plasma hepcidin suppression and iron elevation by Anticalin-derived
      hepcidin antagonist in cynomolgus monkey.
AB  - BACKGROUND AND PURPOSE: Anaemia of chronic disease (ACD) has been linked to iron
      restricted erythropoiesis imposed by high circulating levels of hepcidin, a 25
      amino acid hepatocyte-derived peptide that controls systemic iron homeostasis.
      Here, we report the engineering of the human lipocalin-derived, small protein
      based anticalin PRS-080 hepcidin antagonist with high affinity and selectivity.
      EXPERIMENTAL APPROACH: Anticalin- and hepcidin-specific pharmacokinetic
      (PK)/pharmacodynamic modelling (PD) was used to design and select the suitable
      drug candidate based on t1/2 extension and duration of hepcidin suppression. The
      development of a novel free hepcidin assay enabled accurate analysis of bioactive
      hepcidin suppression and elucidation of the observed plasma iron levels after PRS
      080-PEG30 administration in vivo. KEY RESULTS: PRS-080 had a hepcidin-binding
      affinity of 0.07 nM and, after coupling to 30 kD PEG (PRS-080-PEG30), a t1/2 of
      43 h in cynomolgus monkeys. Dose-dependent iron mobilization and hepcidin
      suppression were observed after a single i.v. dose of PRS-080-PEG30 in cynomolgus
      monkeys. Importantly, in these animals, suppression of free hepcidin and
      subsequent plasma iron elevation were sustained during repeated s.c. dosing.
      After repeated dosing and followed by a treatment-free interval, all iron
      parameters returned to pre-dose values. CONCLUSIONS AND IMPLICATIONS: In
      conclusion, we developed a dose-dependent and safe approach for the direct
      suppression of hepcidin, resulting in prolonged iron mobilization to alleviate
      iron-restricted erythropoiesis that can address the root cause of ACD. PRS-080
      PEG30 is currently in early clinical development.

PMID- 29329505
TI  - Tips to avoid complications related to direct cannulation of the axillary artery.

PMID- 29329506
TI  - Response to 'Finding the perfect sclerosant - is it possible?'

PMID- 29329507
TI  - Differences in salaries of physician assistants in the USA by race, ethnicity and
      sex.
AB  - Objectives Data from the Academy of American Physician Assistants have suggested
      there are no differences in salaries by race and ethnic group. Our objective was
      to compare salaries of physician assistants for different racial and ethnic
      groups and sexes using another data source. Methods Data from the American
      Community Surveys (2010-2012) to examine pay differentials of physician
      assistants. Ordinary least squares regression analysis to compare the salaries of
      males and females, and those of racial and ethnic groups. Results The majority of
      physician assistants in recent decades have been women. Their salaries are
      substantially below those of their male counterparts. The number from racial and
      ethnic minorities remains low. American Community Surveys data show salaries to
      be lower than that reported by the American Academy of Physician Assistants. The
      salaries of Black and Hispanic physician assistants lag significantly behind the
      salaries of those who are White. Conclusions American Community Surveys data
      suggest that previously published Academy of American Physician Assistants survey
      data may have been biased with a low percentage of physician assistants from
      racial and ethnic minorities which suggests that the Academy of American
      Physician Assistants need to focus on recruiting greater numbers of minorities.

PMID- 29329508
TI  - Hospital readmissions and the day of the week.
AB  - Objectives Patients discharged from hospitals on a Friday (Friday discharges) are
      readmitted sooner (a shorter time-to-emergency-readmission) than those discharged
      on any other day of the week. To evaluate the cost-effectiveness of increasing
      weekend capacity, the effect estimate of Friday discharge on time-to-emergency
      readmission needs to be precise. However, precise effect estimation is
      complicated by the confounding effect of differing healthcare-seeking behaviour
      and admission practices, and therefore different admission probability, by day of
      the week. The objective of this research was to examine how differing admission
      probability by day of the week influences the effect of discharge day on time-to
      emergency-readmission. Methods We used a Markov model to determine how day of the
      week admission probability would theoretically affect the time-to-emergency
      readmission for Friday and Wednesday discharges. We tested this in a cohort of
      patients who have had a history of respiratory illness, using a Cox proportional
      hazards model to fit the time-to-emergency-readmission to any Quebec hospital as
      a function of the day of the week of discharge and admission. We fitted another
      Cox model with an additional time-varying covariate for the current day of the
      week, to model differing admission probabilities by day of the week. Results Our
      Markov model showed that if admission probability is lower on the weekends,
      Friday discharges will be readmitted later (longer time-to-emergency-readmission)
      than Wednesday discharges. Using hospital admission data, we found that Friday
      discharges were readmitted slightly earlier than Wednesday discharges (HR: 1.03,
      95% CI: (1.02, 1.05)). After adding a time-varying covariate for the current day
      of the week, the length of time-to-emergency-readmission for a Friday discharge
      increased, but it was still earlier than a Wednesday discharge (HR: 1.04, 95% CI:
      (1.01, 1.07)). Conclusions The lower admission probabilities on the weekend
      confound the effect of Friday discharge on time-to-emergency-readmission by
      increasing the time-to-emergency-readmission. This confounding effect causes an
      underestimate of the effect of Friday discharge on time-to-emergency-readmission.

PMID- 29329509
TI  - Audit of submissions: July 2016-June 2017.

PMID- 29329510
TI  - The predictive value of hunger score on gastric evacuation after oral intake of
      carbohydrate solution.
AB  - BACKGROUND: Surgical patients are asked to fast for a sufficient duration to
      ensure that the amount of residual liquid in the stomach is within the safe
      range, thereby reducing the risk of gastric reflux perioperatively. The authors
      hypothesized that subjective hunger numerical rating scale (NRS) score could also
      help assess the process of gastric emptying and determine the amount of fluid
      remaining in the stomach. METHODS: The current study consisted of healthy
      volunteers recruited by advertisement and mutual introduction. Participants were
      asked to rate their subjective hunger feeling every 30 min after oral
      administration of 8 mL/kg carbohydrate nutrient solution that contained 10%
      maltodextrin and 2.5% sucrose. Consecutively, the gastric residual fluid was
      measured by magnetic resonance imagining (MRI). The Spearman's correlation
      coefficient, the ROC curves and the stepwise regression were used to analyze the
      predictive value of NRS for the gastric emptying process. RESULTS: The cohort
      consisted of 29 healthy volunteers enrolled in this study. The area under ROC
      curves estimated by the NRS score for the gastric residual volume of 2 mL/kg, 1
      mL/kg, and 0.5 mL/kg were AUC2.0 = 0.78, AUC1.0 = 0.76, and AUC0.5 = 0.72,
      respectively. The correlation coefficient between the NRS score and the residual
      liquid in the stomach was -0.57 (P < 0.01). The correlation coefficient between
      the increase of the NRS score and the decrease of gastric liquid residual volume
      was 0.46 (P < 0.01). The standardized estimate of NRS score for the residual
      volume was -0.18 (P < 0.01) and the standardized estimate of fasting time was 
      0.73 (P < 0.01). CONCLUSIONS: The subjective hunger NRS score can not accurately
      predict the gastric residual volume, but it can provide a reference for
      clinicians to judge the gastric emptying process and it should be used as a
      second check after oral intake of clear fluids before surgery according to the
      new fasting protocol.

PMID- 29329511
TI  - Classifying and characterizing the development of adaptive behavior in a
      naturalistic longitudinal study of young children with autism.
AB  - BACKGROUND: Adaptive behavior, or the ability to function independently in ones'
      environment, is a key phenotypic construct in autism spectrum disorder (ASD). Few
      studies of the development of adaptive behavior during preschool to school-age
      are available, though existing data demonstrate that the degree of ability and
      impairment associated with ASD, and how it manifests over time, is heterogeneous.
      Growth mixture models are a statistical technique that can help parse this
      heterogeneity in trajectories. METHODS: Data from an accelerated longitudinal
      natural history study (n = 105 children with ASD) were subjected to growth
      mixture model analysis. Children were assessed up to four times between the ages
      of 3 to 7.99 years. RESULTS: The best fitting model comprised two classes of
      trajectory on the Adaptive Behavior Composite score of the Vineland Adaptive
      Behavior Scale, Second Edition-a low and decreasing trajectory (73% of the
      sample) and a moderate and stable class (27%). CONCLUSIONS: These results
      partially replicate the classes observed in a previous study of a similarly
      characterized sample, suggesting that developmental trajectory may indeed serve
      as a phenotype. Further, the ability to predict which trajectory a child is
      likely to follow will be useful in planning for clinical trials.

PMID- 29329512
TI  - Landscape and rodent community composition are associated with risk of
      hemorrhagic fever with renal syndrome in two cities in China, 2006-2013.
AB  - BACKGROUND: Hemorrhagic fever with renal syndrome (HFRS) is a rodent-borne
      disease caused by hantaviruses. Landscape can influence the risk of hantavirus
      infection for humans, mainly through its effect on rodent community composition
      and distribution. It is important to understand how landscapes influence
      population dynamics for different rodent species and the subsequent effect on
      HFRS risk. METHODS: To determine how rodent community composition influenced
      human hantavirus infection, we monitored rodent communities in the prefecture
      level cities of Loudi and Shaoyang, China, from 2006 to 2013. Land use data were
      extracted from satellite images and rodent community diversity was analyzed in 45
      trapping sites, in different environments. Potential contact matrices,
      determining how rodent community composition influence HFRS infection among
      different land use types, were estimated based on rodent community composition
      and environment type for geo-located HFRS cases. RESULTS: Apodemus agrarius and
      Rattus norvegicus were the predominant species in Loudi and Shaoyang,
      respectively. The major risk of HFRS infection was concentrated in areas with
      cultivated land and was associated with A. agrarius, R. norvegicus, and Rattus
      flavipectus. In urban areas in Shaoyang, Mus musculus was related to risk of
      hantavirus infection. CONCLUSIONS: Landscape features and rodent community
      dynamics may affect the risk of human hantavirus infection. Results of this study
      may be useful for the development of HFRS prevention initiatives that are
      customized for regions with different geographical environments.

PMID- 29329513
TI  - The behavioural phenotype of Potocki-Lupski syndrome: a cross-syndrome
      comparison.
AB  - BACKGROUND: Potocki-Lupski syndrome (PTLS) and Smith-Magenis syndrome (SMS) are
      related genomic disorders, as duplication 17p11.2 (associated with PTLS) is the
      reciprocal recombination product of the SMS microdeletion. While SMS has a
      relatively well-delineated behavioural phenotype, the behavioural profile in PTLS
      is less well defined, despite purported associations with autism spectrum
      disorder (ASD) and the suggestion that some behaviours may be diametric to those
      seen in SMS. METHODS: Caregivers of individuals with PTLS (N = 34; M age = 12.43,
      SD = 6.78) completed online behavioural questionnaires, including the Challenging
      Behaviour Questionnaire (CBQ), the Activity Questionnaire (TAQ), the Repetitive
      Behaviour Questionnaire (RBQ), the Mood, Interest and Pleasure Questionnaire
      Short Form (MIPQ-S) and the Social Communication Questionnaire (SCQ), which
      assesses behaviours associated with ASD. Individuals with PTLS were matched on
      age and adaptive functioning to individuals with SMS (N = 31; M age = 13.61, SD =
      6.85) and individuals with idiopathic ASD (N = 33; M age = 12.04, SD = 5.85) from
      an existing dataset. RESULTS: Individuals with PTLS and SMS were less impaired
      than those with idiopathic ASD on the communication and reciprocal social
      interaction subscales of the SCQ, but neither syndrome group differed from
      idiopathic ASD on the restricted, repetitive and stereotyped behaviours subscale.
      On the repetitive behaviour measure, individuals with PTLS and idiopathic ASD
      scored higher than individuals with SMS on the compulsive behaviour subscale.
      Rates of self-injury and property destruction were significantly lower in PTLS
      and idiopathic ASD than in SMS. No between-syndrome differences were found in
      relation to overactivity or mood; however, impulsivity was greater in SMS than in
      PTLS. CONCLUSIONS: Findings suggest some overlap in the behavioural phenotype of
      PTLS and features of ASD symptomatology; however, the overall profile of
      behaviours in PTLS appears to be divergent from both idiopathic ASD and SMS.
      Relative to idiopathic ASD, PTLS is not characterised by communication or social
      interaction deficits. However, restricted and repetitive behaviours were evident
      in PTLS, and these may be characterised specifically by compulsive behaviours.
      While several behavioural differences were identified between PTLS and SMS, there
      was little evidence of diametric behavioural phenotypes, particularly in relation
      to social behaviour.

PMID- 29329514
TI  - Correction to: Short- and long-term outcomes in infective endocarditis patients:
      a systematic review and meta-analysis.
AB  - CORRECTION: Unfortunately, after publication of this article [1], it was noticed
      that the name of the fifth author was incorrectly displayed as Akshaya Srikanth
      Bahagavathula. The correct name is Akshaya Srikanth Bhagavathula and can be seen
      in the corrected author list above. The original article has also been updated to
      correct this error.

PMID- 29329516
TI  - Bilateral giant retinal tears in Osteogenesis Imperfecta.
AB  - BACKGROUND: Osteogenesis imperfecta (OI) is a rare primarily autosomal dominant
      condition in which the connective tissues of bones, ligaments and sclerae do not
      form properly. Typically, mutations in COL1A1 and COL1A2 genes lead to the
      defective formation or quantity of type I collagen, the principle matrix in these
      tissues. Molecular genetic studies have now elucidated multiple genetic subtypes
      of the disorder but little literature exists on the risk of retinal tears and
      detachments in OI. CASE PRESENTATION: We report the first case of a child with a
      rare recessive type of OI, subtype VIII, resulting from a P3H1 (also known as
      LEPRE1) gene mutation presenting with bilateral giant retinal tears and the
      surgical challenges encountered in performing retinal detachment repair due to
      scleral thinning. The P3H1 gene encodes for prolyl 3-hydroxylase 1 which is
      involved in the post-translational modification of not only collagen type I but
      also types II and V which when mutated may result in pathological posterior
      vitreous detachment (PVD) and giant retinal tear detachments. CONCLUSIONS:
      Genetic analyses are increasingly important in such cases and may guide patient
      monitoring and potential prophylactic treatment, known to significantly reduce
      the probability of giant retinal tear detachments in other high-risk
      collagenopathies such as Stickler Syndrome Type I.

PMID- 29329515
TI  - Engaging clinicians and patients to assess and improve frailty measurement in
      adults with end stage renal disease.
AB  - BACKGROUND: The Fried frailty phenotype, a measure of physiologic reserve defined
      by 5 components (exhaustion, unintentional weight loss, low physical activity,
      slow walking speed, and poor grip strength), is associated with poor outcomes
      among ESRD patients. However, these 5 components may not fully capture
      physiologic reserve in this population. We aimed to ascertain opinions of ESRD
      clinicians and patients about the usefulness of the Fried frailty phenotype and
      interventions to improve frailty in ESRD patients, and to identify novel
      components to further characterize frailty in ESRD. METHODS: Clinicians who treat
      adults with ESRD completed a 2-round Delphi study (n = 41 and n = 36,
      respectively; response rate = 87%). ESRD patients completed a survey at
      transplant evaluation (n = 460; response rate = 81%). We compared clinician and
      patient opinions on the constituent components of frailty. RESULTS: Clinicians
      were more likely than patients to say that ESRD makes patients frail (97.6% vs.
      60.2%). There was consensus among clinicians that exhaustion, low physical
      activity, slow walking speed, and poor grip strength characterize frailty in ESRD
      patients; however, 29% of clinicians thought weight loss was not relevant.
      Patients were less likely than clinicians to say that the 5 Fried frailty
      components were relevant. Clinicians identified 10 new ESRD-specific potential
      components including falls (64%), physical decline (61%), and cognitive
      impairment (39%). Clinicians (83%) and patients (80%) agreed that intradialytic
      foot-peddlers might make ESRD patients less frail. CONCLUSIONS: There was
      consensus among clinicians and moderate consensus among patients that frailty is
      more common in ESRD. Weight loss was not seen as relevant, but new components
      were identified. These findings are first steps in refining the frailty phenotype
      and identifying interventions to improve physiologic reserve specific to ESRD
      patients.

PMID- 29329517
TI  - Genome-wide analyses of direct target genes of four rice NAC-domain transcription
      factors involved in drought tolerance.
AB  - BACKGROUND: Plant stress responses and mechanisms determining tolerance are
      controlled by diverse sets of genes. Transcription factors (TFs) have been
      implicated in conferring drought tolerance under drought stress conditions, and
      the identification of their target genes can elucidate molecular regulatory
      networks that orchestrate tolerance mechanisms. RESULTS: We generated transgenic
      rice plants overexpressing the 4 rice TFs, OsNAC5, 6, 9, and 10, under the
      control of the root-specific RCc3 promoter. We showed that they were tolerant to
      drought stress with reduced loss of grain yield under drought conditions compared
      with wild type plants. To understand the molecular mechanisms underlying this
      tolerance, we here performed chromatin immunoprecipitation (ChIP)-Seq and RNA-Seq
      analyses to identify the direct target genes of the OsNAC proteins using the
      RCc3:6MYC-OsNAC expressing roots. A total of 475 binding loci for the 4 OsNAC
      proteins were identified by cross-referencing their binding to promoter regions
      and the expression levels of the corresponding genes. The binding loci were
      distributed among the promoter regions of 391 target genes that were directly up
      regulated by one of the OsNAC proteins in four RCc3:6MYC-OsNAC transgenic lines.
      Based on gene ontology (GO) analysis, the direct target genes were related to
      transmembrane/transporter activity, vesicle, plant hormones, carbohydrate
      metabolism, and TFs. The direct targets of each OsNAC range from 4.0-8.7% of the
      total number of up-regulated genes found in the RNA-Seq data sets. Thus, each
      OsNAC up-regulates a set of direct target genes that alter root system
      architecture in the RCc3:OsNAC plants to confer drought tolerance. Our results
      provide a valuable resource for functional dissection of the molecular mechanisms
      of drought tolerance. CONCLUSIONS: Many of the target genes, including
      transmembrane/transporter, vesicle related, auxin/hormone related, carbohydrate
      metabolic processes, and transcription factor genes, that are up-regulated by
      OsNACs act as the cellular components which would alter the root architectures of
      RCc3:OsNACs for drought tolerance.

PMID- 29329518
TI  - The use of eculizumab in gemcitabine induced thrombotic microangiopathy.
AB  - BACKGROUND: Thrombotic microangiopathy (TMA) secondary to gemcitabine therapy
      (GiTMA) is a very rare pathology that carries a poor prognosis, with nearly half
      of the cases progressing to end stage renal disease. GiTMA is most commonly
      associated with adenocarcinomas, most notably pancreatic cancers. The mainstay of
      management is withdrawal of the offending drug and supportive care.
      Plasmapheresis has a limited role and hemodialysis may help in the management of
      fluid overload secondary to renal failure. Furthermore, a C5 inhibitor,
      eculizumab, has been successfully used in the treatment of GiTMA. CASE
      PRESENTATION: A 64-year-old Caucasian female with history of pancreatic
      adenocarcinoma on gemcitabine chemotherapy presented with signs and symptoms of
      fluid overload and was found to have abnormal kidney function. Her BP was 195/110
      mmHg, serum creatinine 4.48 mg/dl, hemoglobin 8.2 g/dl, platelets 53 * 103/cmm,
      lactate dehydrogenase 540 IU/L, and was found to have schistocytes on blood film.
      A diagnosis of TMA secondary to gemcitabine therapy was suspected. Hemodialysis
      for volume overload and daily plasmapheresis were initiated. After six days of
      plasmapheresis, renal function did not improve. Further work up revealed ADAMTS
      13 activity >15%, low C3, and stool culture and Shiga-toxin PCR were negative.
      Renal biopsy was consistent with TMA. Gemcitabine was discontinued, but renal
      function failed to improve and eculizumab therapy was considered due to suspicion
      of aHUS. Serum creatinine >2.26 mg/dl and a platelet count of >/= 30 * 109/L is
      highly suggestive of aHUS, while TTP is more likely when creatinine is <2.26
      mg/dl and platelet count of <30 * 109/L. She received intravenous eculizumab for
      eight months, which resulted in significant improvement of renal function. Other
      markers of hemolysis, namely LDH and bilirubin, also rapidly improved following
      eculizumab therapy. Plasmapheresis and hemodialysis were discontinued after two
      and eight weeks of initiation respectively. CONCLUSION: Chemotherapy induced TMA
      is very rare and requires a high index of clinical suspicion for timely
      diagnosis. Discontinuation of the offending drug and supportive care is the main
      stay of treatment; however, eculizumab has been shown to be beneficial in GiTMA.
      Further research is required to validate this approach.

PMID- 29329519
TI  - Eikenella corrodens endocarditis and liver abscess in a previously healthy male,
      a case report.
AB  - BACKGROUND: Eikenella corrodens is one of the HACEK bacteria constituting part of
      the normal flora of the oropharynx, however, still an uncommon pathogen. We
      report a case of a large Eikenella corrodens liver abscess with simultaneously
      endocarditis in a previously healthy male. CASE PRESENTATION: A 49-year-old
      Danish man was admitted because of one-month malaise, fever, cough and
      unintentional weight loss. On admission there was elevated white blood cell count
      and C-reactive protein, as well as affected liver function tests. Initially
      pneumonia was suspected, but due to lack of improvement on pneumonia treatment, a
      PET-CT scan was performed, which showed a large multiloculated abscess in the
      liver. The abscess was drained using ultrasound guidance. Culture demonstrated
      Eikenella corrodens. Transesophageal echocardiography revealed aortic
      endocarditis. The patient was treated with antibiotics and abscess drainage, on
      which he slowly improved. He was discharged after 1.5 months of hospitalisation.
      On follow-up 2 months later, the patient was asymptomatic with normalized
      biochemistry and ultrasound showed complete regression of the abscess.
      CONCLUSIONS: This is the first case of documented Eikenella corrodens concurrent
      liver abscess and endocarditis. The case report highlights that Eikenella
      corrodens should be considered as a cause of liver abscess. Empirical treatment
      of pyogenic liver abscess will most often cover Eikenella corrodens, but the
      recommended treatment is a third generation cephalosporin or a fluoroquinolon. A
      multiloculated liver abscess may require drainage several times during treatment.
      The finding of Eikenella corrodens should elicit an echocardiography to diagnose
      endocarditis even in patients without clinical signs of endocarditis.

PMID- 29329520
TI  - Effects of primary care clinician beliefs and perceived organizational
      facilitators on the delivery of preventive care to individuals with mental
      illnesses.
AB  - BACKGROUND: Although many studies have documented patient-, clinician-, and
      organizational barriers/facilitators of primary care among people with mental
      illnesses, few have examined whether these factors predict actual rates of
      preventive service use. We assessed whether clinician behaviors, beliefs,
      characteristics, and clinician-reported organizational characteristics, predicted
      delivery of preventive services in this population. METHODS: Primary care
      clinicians (n = 247) at Kaiser Permanente Northwest (KPNW) or community health
      centers and safety-net clinics (CHCs), in six states, completed clinician surveys
      in 2014. Using electronic health record data, we calculated preventive care-gap
      rates for patients with mental illnesses empaneled to survey respondents (n =
      37,251). Using separate multi-level regression models for each setting, we tested
      whether survey responses predicted preventive service care-gap rates. RESULTS:
      After controlling for patient-level characteristics, patients of clinicians who
      reported a greater likelihood of providing preventive care to psychiatrically
      asymptomatic patients experienced lower care-gap rates (KPNW gamma= - .05, p =
      .041; CHCs gamma= - .05, p = .033). In KPNW, patients of female clinicians had
      fewer care gaps than patients of male clinicians (gamma= - .07, p = .011). In
      CHCs, patients of clinicians who had practiced longer had fewer care gaps (gamma=
      - .004, p = .010), as did patients whose clinicians believed that organizational
      quality goals facilitate preventive service provision (gamma= - .06, p = .006).
      Case manager availability in CHCs was associated with higher care-gap rates
      (gamma=.06, p = .028). CONCLUSIONS: Clinicians who report they are likely to
      address preventive concerns when their mentally ill patients present without
      apparent psychiatric symptoms had patients with fewer care gaps. In CHCs, care
      quality goals may facilitate preventive care whereas case managers may not.

PMID- 29329521
TI  - Treating C3 glomerulopathy with eculizumab.
AB  - BACKGROUND: C3 glomerulopathy (C3G) is a rare, but severe glomerular disease with
      grim prognosis. The complex pathogenesis is just unfolding, and involves acquired
      as well as inherited dysregulation of the alternative pathway of the complement
      cascade. Currently, there is no established therapy. Treatment with the C5
      complement inhibitor eculizumab may be a therapeutic option. However, due to
      rarity of the disease, parameters predicting treatment response remain largely
      unknown. METHODS: Seven patients with C3G (five with C3 glomerulonephritis and
      two with dense deposit disease) were treated with eculizumab. Subjects underwent
      biopsy before enrollment. The histopathology, clinical data, and response to
      eculizumab treatment were analyzed. The key parameters to determine outcome were
      changes of serum creatinine and urinary protein over time. RESULTS: After
      treatment with eculizumab, four subjects showed significantly improved or stable
      renal function and urinary protein. A positive response occurred between 2 weeks
      and 6 months after therapy initiation. One subject (with allograft recurrent C3
      glomerulonephritis) initially showed a positive response, but relapsed when
      eculizumab was discontinued, and did not respond after re-initiation of
      treatment. Two subjects showed impaired renal function and increasing urinary
      protein despite therapy with eculizumab. CONCLUSIONS: Eculizumab may be a
      therapeutic option for a subset of C3G patients. The response to eculizumab is
      heterogeneous, and early as well as continuous treatment may be necessary to
      prevent disease progression. These findings emphasize the need for studies
      identifying genetic and functional complement abnormalities that may help to
      guide eculizumab treatment and predict response.

PMID- 29329522
TI  - A-GAME: improving the assembly of pooled functional metagenomics sequence data.
AB  - BACKGROUND: Expression screening of environmental DNA (eDNA) libraries is a
      popular approach for the identification and characterization of novel microbial
      enzymes with promising biotechnological properties. In such "functional
      metagenomics" experiments, inserts, selected on the basis of activity assays, are
      sequenced with high throughput sequencing technologies. Assembly is followed by
      gene prediction, annotation and identification of candidate genes that are
      subsequently evaluated for biotechnological applications. RESULTS: Here we
      present A-GAME (A GAlaxy suite for functional MEtagenomics), a web service
      incorporating state of the art tools and workflows for the analysis of eDNA
      sequence data. We illustrate the potential of A-GAME workflows using real
      functional metagenomics data, showing that they outperform alternative
      metagenomics assemblers. Dedicated tools available in A-GAME allow efficient
      analysis of pooled libraries and rapid identification of candidate genes,
      reducing sequencing costs and saving the need for laborious manual annotation.
      CONCLUSION: In conclusion, we believe A-GAME will constitute a valuable resource
      for the functional metagenomics community. A-GAME is publicly available at
      http://beaconlab.it/agame.

PMID- 29329523
TI  - Early commitment of cardiovascular autonomic modulation in Brazilian patients
      with congenital generalized lipodystrophy.
AB  - BACKGROUND: Metabolic abnormalities in congenital generalized lipodystrophy (CGL)
      are associated with microvascular complications. However, the evaluation of
      different types of neuropathy in these patients, including the commitment of
      cardiovascular autonomic modulation, is scarce. The objective of the present
      study was to determine the prevalence of cardiovascular autonomic neuropathy
      (CAN) in patients with CGL compared with individuals with type 1 diabetes and
      healthy subjects. METHODS: Ten patients with CGL, 20 patients with type 1
      diabetes and 20 healthy subjects were included in the study. Controls were paired
      1:2 for age, gender, BMI and pubertal stage. Heart rate variability (HRV) was
      analyzed using cardiovascular autonomic reflex tests, including postural
      hypotension test, Valsalva (VAL), respiratory (E/I) and orthostatic (30/15)
      coefficients, and spectral analysis of the HRV, determining very low (VLF), low
      (LF) and high (HF) frequencies components. The diagnosis of CAN was defined as
      the presence of at least two altered tests. RESULTS: CAN was detected in 40% of
      the CGL patients, 5% in type 1 diabetes patients and was absent in healthy
      individuals (p < 0.05). We observed a significant reduction in the E/I, VLF, LF
      and HF in CGL cases vs. type 1 diabetes and healthy individuals and lower levels
      of 30/15 and VAL in CGL vs. healthy individuals. A significant positive
      correlation was observed between leptin and 30/15 coefficient (r = 0.396; p =
      0.036) after adjusting for insulin resistance and triglycerides. Autonomic
      cardiovascular tests were associated with HbA1c, HOMA-IR, triglycerides and
      albumin/creatinine ratio in CGL cases. CONCLUSIONS: We observed a high prevalence
      of CAN in young patients with CGL, suggesting that insulin resistance,
      hypertriglyceridemia and hypoleptinemia, may have been involved in early CAN
      development. Additional studies are needed to evaluate the role of leptinemia in
      the physiopathogenesis of the condition.

PMID- 29329524
TI  - Uncovering the evolutionary history of neo-XY sex chromosomes in the grasshopper
      Ronderosia bergii (Orthoptera, Melanoplinae) through satellite DNA analysis.
AB  - BACKGROUND: Neo-sex chromosome systems arose independently multiple times in
      evolution, presenting the remarkable characteristic of repetitive DNAs
      accumulation. Among grasshoppers, occurrence of neo-XY was repeatedly noticed in
      Melanoplinae. Here we analyzed the most abundant tandem repeats of R. bergii (2n
      = 22, neo-XY?) using deep Illumina sequencing and graph-based clustering in order
      to address the neo-sex chromosomes evolution. RESULTS: The analyses revealed ten
      families of satDNAs comprising about ~1% of the male genome, which occupied
      mainly C-positive regions of autosomes. Regarding the sex chromosomes, satDNAs
      were recorded within centromeric or interstitial regions of the neo-X chromosome
      and four satDNAs occurred in the neo-Y, two of them being exclusive (Rber248 and
      Rber299). Using a combination of probes we uncovered five well-defined
      cytological variants for neo-Y, originated by multiple paracentric inversions and
      satDNA amplification, besides fragmented neo-Y. These neo-Y variants were
      distinct in frequency between embryos and adult males. CONCLUSIONS: The genomic
      data together with cytogenetic mapping enabled us to better understand the neo
      sex chromosome dynamics in grasshoppers, reinforcing differentiation of neo-X and
      neo-Y and revealing the occurrence of multiple additional rearrangements involved
      in the neo-Y evolution of R. bergii. We discussed the possible causes that led to
      differences in frequency for the neo-Y variants between embryos and adults.
      Finally we hypothesize about the role of DNA satellites in R. bergii as well as
      putative historical events involved in the evolution of the R. bergii neo-XY.

PMID- 29329525
TI  - Reporting of heterogeneity of treatment effect in cohort studies: a review of the
      literature.
AB  - BACKGROUND: This article corresponds to a literature review and analyze how
      heterogeneity of treatment (HTE) is reported and addressed in cohort studies and
      to evaluate the use of the different measures to HTE analysis. METHODS:
      prospective cohort studies, in English language, measuring the effect of a
      treatment (pharmacological, interventional, or other) published among 119 core
      clinical journals (defined by the National Library of Medicine) in the last 16
      years were selected in the following data source: Medline. One reviewer randomly
      sampled journal articles with 1: 1 stratification by journal type: high impact
      journals (the New England Journal of Medicine, JAMA, LANCET, Annals of Internal
      Medicine, BMJ and Plos Medicine) and low impact journal (the remaining journals)
      to identify 150 eligible studies. Two reviewers independently and in duplicate
      used standardized piloted forms to screen study reports for eligibility and to
      extract data. They also used explicit criteria to determine whether a cohort
      study reported HTE analysis. Logistic regression was used to examine the
      association of prespecified study characteristics with reporting versus not
      reporting of heterogeneity of treatment effect. RESULTS: One hundred fifty cohort
      studies were included of which 88 (58%) reported HTE analysis. High impact
      journals (Odds Ratio: 3.5, 95% CI: 1.78-7.5; P < 0.001), pharmacological studies
      (Odds Ratio: 0.26, 95% CI: 0.13-0.51; P < 0.001) and studies published after 2014
      (Odds Ratio: 0.5, 95% CI: 0.25-0.97; P = 0.004) were associated with more
      frequent reporting of HTE. 27 (31%) studies which reported HTE used an
      interaction test. CONCLUSION: More than half cohort studies report some measure
      of heterogeneity of treatment effect. Prospective cohort studies published in
      high impact journals, with large sample size, or studying a pharmacological
      treatment are associated with more frequent HTE reporting. The source of funding
      was not associated with HTE reporting. There is a need for guidelines on how to
      perform HTE analyses in cohort studies.

PMID- 29329527
TI  - Emotional and cognitive experiences during the time of diagnosis and decision
      making following a prenatal diagnosis: a qualitative study of males presented
      with congenital heart defect in the fetus carried by their pregnant partner.
AB  - BACKGROUND: Expectant fathers consider the second-trimester obstetric ultrasound
      examination as an important step towards parenthood, but are ill prepared for a
      detection of a fetal anomaly. Inductive research is scarce concerning their
      experiences and needs for support. Consequently, the aim of this study was to
      explore the emotional and cognitive experiences, during the time of diagnosis and
      decision-making, among males presented with congenital heart defect in the fetus
      carried by their pregnant partner. METHODS: Twelve expectant fathers were
      consecutively recruited through two tertiary referral centers for fetal
      cardiology in Sweden, after they had been presented with a prenatal diagnosis of
      congenital heart defect in the fetus carried by their pregnant partner. The
      respondents were interviewed via telephone, and the interviews were analyzed
      using inductive qualitative content analysis. RESULTS: The respondents
      experienced an intense emotional shock in connection with detection. However,
      they set their own needs aside to attend to the supportive needs of their
      pregnant partner, and stressed the importance of an informed joint decision
      regarding whether to continue or terminate the pregnancy. When terminating the
      pregnancy, they experienced a loss of a wanted child, an emotionally intense
      termination procedure, needs of support neglected by professionals, and worries
      about the risk of recurrence in future pregnancies. When continuing the
      pregnancy, they tried to keep a positive attitude about the coming birth, but
      were simultaneously worried about the postnatal situation. CONCLUSIONS: The
      findings illustrate the importance of inclusive care and adequate follow-up
      routines for both expectant parents following a prenatal diagnosis. This includes
      the initial emotional shock, the decisional process, and depending on decision
      reached, the termination or continuation of the pregnancy. Expectant fathers
      presented with a fetal anomaly need adequate follow-up routines to address
      worries about risk of recurrence in future pregnancies and worries about the
      postnatal situation.

PMID- 29329526
TI  - Definitions, measurements and prevalence of fear of childbirth: a systematic
      review.
AB  - BACKGROUND: Fear of Childbirth (FOC) is a common problem affecting women's health
      and wellbeing, and a common reason for requesting caesarean section. The aims of
      this review were to summarise published research on prevalence of FOC in
      childbearing women and how it is defined and measured during pregnancy and
      postpartum, and to search for useful measures of FOC, for research as well as for
      clinical settings. METHODS: Five bibliographic databases in March 2015 were
      searched for published research on FOC, using a protocol agreed a priori. The
      quality of selected studies was assessed independently by pairs of authors.
      Prevalence data, definitions and methods of measurement were extracted
      independently from each included study by pairs of authors. Finally, some of the
      country rates were combined and compared. RESULTS: In total, 12,188 citations
      were identified and screened by title and abstract; 11,698 were excluded and full
      text of 490 assessed for analysis. Of these, 466 were excluded leaving 24 papers
      included in the review, presenting prevalence of FOC from nine countries in
      Europe, Australia, Canada and the United States. Various definitions and
      measurements of FOC were used. The most frequently-used scale was the W-DEQ with
      various cut-off points describing moderate, severe/intense and extreme/phobic
      fear. Different 3-, 4-, and 5/6 point scales and visual analogue scales were also
      used. Country rates (as measured by seven studies using W-DEQ with >=85 cut-off
      point) varied from 6.3 to 14.8%, a significant difference (chi-square = 104.44,
      d.f. = 6, p < 0.0001). CONCLUSIONS: Rates of severe FOC, measured in the same
      way, varied in different countries. Reasons why FOC might differ are unknown, and
      further research is necessary. Future studies on FOC should use the W-DEQ tool
      with a cut-off point of >=85, or a more thoroughly tested version of the FOBS
      scale, or a three-point scale measurement of FOC using a single question as 'Are
      you afraid about the birth?' In this way, valid comparisons in research can be
      made. Moreover, validation of a clinical tool that is more focussed on FOC alone,
      and easier than the longer W-DEQ, for women to fill in and clinicians to
      administer, is required.

PMID- 29329528
TI  - Transmission of measles among healthcare Workers in Hospital W, Xinjiang
      Autonomous Region, China, 2016.
AB  - BACKGROUND: As China approaches the elimination of measles, outbreaks of measles
      continue to occur. Healthcare workers (HCWs) are known to be at high risk of
      infection and transmission of measles virus. A measles outbreak occurred in a
      hospital in Xinjiang Uighur Autonomous Region of the People's Republic of China.
      We report an investigation of this outbreak and its implications for measles
      elimination and outbreak preparedness. METHODS: We conducted a retrospective
      search for measles cases using hospital records. Information on cases was
      collected by interview, and was used to determine epidemiological linkages. We
      surveyed HCWs to determine their demographic characteristics, disease history and
      vaccination status, and knowledge about measles. RESULTS: We identified 19 cases,
      ages 18 to 45 years, in Hospital W between December 2015 and January 2016; 14
      were laboratory-confirmed, and 5 were epidemiologically linked. The primary case
      was a 25-year-old neurology department nurse who developed a rash on 22 December
      2015 that was reported on 11 January 2016. She continued working and living with
      her workmates in a dormitory during her measles transmission period. Among the 19
      infected HCWs, 2 had received a dose of measles-containing vaccine (MCV) before
      the outbreak, and 16 had unknown vaccination status. Outbreak response
      immunization activities were started on 8 January in a non-selective manner by
      offering vaccine regardless of vaccination history; 605(68%) of 890 HCWs were
      vaccinated. The HCW survey had a 73% response rate (646/890); 41% of HCWs
      reported that they had received MCV before outbreak, and 56% exhibited good
      knowledge of measles symptoms, transmission, complications, and vaccination.
      CONCLUSIONS: Low MCV coverage, low measles knowledge among HCWs, delayed
      reporting of measles cases, and absence of proper case management were associated
      with this outbreak. Training and vaccinating HCWs against measles are essential
      activities to prevent measles virus transmission among HCWs.

PMID- 29329529
TI  - Resilience and well-being of university nursing students in Hong Kong: a cross
      sectional study.
AB  - BACKGROUND: University nursing students experience higher levels of academic
      stress than those of other disciplines. Academic stress leads to psychological
      distress and has detrimental effects on well-being. The ability to overcome such
      adversity and learn to be stronger from the experience is regarded as resilience.
      Resilience is found to have an impact on learning experience, academic
      performance, course completion and, in the longer term, professional practice.
      Resilience and positive coping strategies can resist stress and improve personal
      well-being. However, the relationship between resilience and well-being remains
      unexplored in nursing students, which are significant attributes to their
      academic success and future career persistence. METHODS: The study was a cross
      sectional descriptive correlational design. Inclusion criteria for recruitment
      was students studying pre-registration nursing programmes at both undergraduate
      and postgraduate levels. The 10-item Connor-Davidson Resilience Scale (CD-RISC
      10) and World Health Organisation-5 Well-Being Index (WHO-5) were used to measure
      resilience and psychological well-being respectively. RESULTS: A convenience
      sample of 678 university nursing students was recruited from a university. The
      mean score of CD-RISC-10 was 24.0. When comparing the resilience levels of
      undergraduate and postgraduate students, the total scores were found to be 23.8
      and 24.9 respectively. There was a statistically significant difference between
      the groups (p = .020). With regard to perceived well-being, the mean score of WHO
      5 was 15.5. There was no significant difference between undergraduates and
      postgraduates (p = .131). Bivariate analysis showed that self-reported resilience
      had a medium, positive correlation with perceived well-being (r = .378, p =
      .000), and senior students had significantly higher level of perceived well-being
      than junior students (16.0 vs 15.1, p = .003). Multivariable regression analysis
      on perceived well-being indicated that self-reported resilience emerged as a
      significant predictor of perceived well-being (regression coefficient B = 0.259;
      p < .001). CONCLUSIONS: The results demonstrate that nursing students with a high
      level of resilience have better perceived well-being, and the level of resilience
      of postgraduates was significantly higher than that of undergraduates. Therefore,
      educational strategies should be developed in the nursing curriculum and a
      supportive learning environment should be created to foster resilience in the
      students.

PMID- 29329530
TI  - Design and evaluation of a mobile application to assist the self-monitoring of
      the chronic kidney disease in developing countries.
AB  - BACKGROUND: The chronic kidney disease (CKD) is a worldwide critical problem,
      especially in developing countries. CKD patients usually begin their treatment in
      advanced stages, which requires dialysis and kidney transplantation, and
      consequently, affects mortality rates. This issue is faced by a mobile health
      (mHealth) application (app) that aims to assist the early diagnosis and self
      monitoring of the disease progression. METHODS: A user-centered design (UCD)
      approach involving health professionals (nurse and nephrologists) and target
      users guided the development process of the app between 2012 and 2016. In-depth
      interviews and prototyping were conducted along with healthcare professionals
      throughout the requirements elicitation process. Elicited requirements were
      translated into a native mHealth app targeting the Android platform. Afterward,
      the Cohen's Kappa coefficient statistics was applied to evaluate the agreement
      between the app and three nephrologists who analyzed test results collected from
      60 medical records. Finally, eight users tested the app and were interviewed
      about usability and user perceptions. RESULTS: A mHealth app was designed to
      assist the CKD early diagnosis and self-monitoring considering quality attributes
      such as safety, effectiveness, and usability. A global Kappa value of 0.7119
      showed a substantial degree of agreement between the app and three nephrologists.
      Results of face-to-face interviews with target users indicated a good user
      satisfaction. However, the task of CKD self-monitoring proved difficult because
      most of the users did not fully understand the meaning of specific biomarkers
      (e.g., creatinine). CONCLUSION: The UCD approach provided mechanisms to develop
      the app based on the real needs of users. Even with no perfect Kappa degree of
      agreement, results are satisfactory because it aims to refer patients to
      nephrologists in early stages, where they may confirm the CKD diagnosis.

PMID- 29329531
TI  - Chemical genomic guided engineering of gamma-valerolactone tolerant yeast.
AB  - BACKGROUND: Gamma valerolactone (GVL) treatment of lignocellulosic bomass is a
      promising technology for degradation of biomass for biofuel production; however,
      GVL is toxic to fermentative microbes. Using a combination of chemical genomics
      with the yeast (Saccharomyces cerevisiae) deletion collection to identify
      sensitive and resistant mutants, and chemical proteomics to monitor protein
      abundance in the presence of GVL, we sought to understand the mechanism toxicity
      and resistance to GVL with the goal of engineering a GVL-tolerant, xylose
      fermenting yeast. RESULTS: Chemical genomic profiling of GVL predicted that this
      chemical affects membranes and membrane-bound processes. We show that GVL causes
      rapid, dose-dependent cell permeability, and is synergistic with ethanol.
      Chemical genomic profiling of GVL revealed that deletion of the functionally
      related enzymes Pad1p and Fdc1p, which act together to decarboxylate cinnamic
      acid and its derivatives to vinyl forms, increases yeast tolerance to GVL.
      Further, overexpression of Pad1p sensitizes cells to GVL toxicity. To improve GVL
      tolerance, we deleted PAD1 and FDC1 in a xylose-fermenting yeast strain. The
      modified strain exhibited increased anaerobic growth, sugar utilization, and
      ethanol production in synthetic hydrolysate with 1.5% GVL, and under other
      conditions. Chemical proteomic profiling of the engineered strain revealed that
      enzymes involved in ergosterol biosynthesis were more abundant in the presence of
      GVL compared to the background strain. The engineered GVL strain contained
      greater amounts of ergosterol than the background strain. CONCLUSIONS: We found
      that GVL exerts toxicity to yeast by compromising cellular membranes, and that
      this toxicity is synergistic with ethanol. Deletion of PAD1 and FDC1 conferred
      GVL resistance to a xylose-fermenting yeast strain by increasing ergosterol
      accumulation in aerobically grown cells. The GVL-tolerant strain fermented sugars
      in the presence of GVL levels that were inhibitory to the unmodified strain. This
      strain represents a xylose fermenting yeast specifically tailored to GVL produced
      hydrolysates.

PMID- 29329532
TI  - Functionality of hospital information systems: results from a survey of quality
      directors at Turkish hospitals.
AB  - BACKGROUND: We aimed to determine availability of core Hospital Information
      Systems (HIS) functions implemented in Turkish hospitals and the perceived
      importance of these functions on quality and patient safety. METHODS: We surveyed
      quality directors (QDs) at civilian hospitals in the nation of Turkey. Data were
      collected via web survey using an instrument with 50 items describing core
      functionality of HIS. We calculated mean availability of each function, mean and
      median values of perceived impact on quality, and we investigated the
      relationship between availability and perceived importance. RESULTS: We received
      responses from 31% of eligible institutions, representing all major geographic
      regions of Turkey. Mean availability of 50 HIS functions was 65.6%, ranging from
      19.6% to 97.4%. Mean importance score was 7.87 (on a 9-point scale) ranging from
      7.13 to 8.41. Functions related to result management (89.3%) and decision support
      systems (52.2%) had the highest and lowest reported availability respectively.
      Availability and perceived importance were moderately correlated (r = 0.52).
      CONCLUSION: QDs report high importance of the HIS functions surveyed as they
      relate to quality and patient safety. Availability and perceived importance of
      HIS functions are generally correlated, with some interesting exceptions. These
      findings may inform future investments and guide policy changes within the
      Turkish healthcare system. Financial incentives, regulations around certified
      HIS, revisions to accreditation manuals, and training interventions are all
      policies which will help integrate HIS functions to support quality and patient
      safety in Turkish hospitals.

PMID- 29329533
TI  - Nutritional status of in-school children and its associated factors in
      Denkyembour District, eastern region, Ghana: comparing schools with feeding and
      non-school feeding policies.
AB  - BACKGROUND: Childhood malnutrition still remains a major public health problem
      impacting negatively on the academic aptitude of school-aged children (SAC)
      particularly in limited resource countries. The Government of Ghana in
      collaboration with the Dutch Government introduced the school feeding programme
      (SFP) to boost the nutritional status of SAC in the country. This study sought to
      compare the nutritional status of SAC enrolled in schools with the SFP and SAC
      enrolled in schools without the SFP in place for the purpose of identifying which
      group has the higher rate of malnutrition. METHODS: A multi-stage sampling was
      used to select 359 SAC between 5 and 12 years who are enrolled in primary one to
      six. Twelve public schools were selected, of which 6 schools benefit from the SFP
      and the other six do not. Anthropometric measurements were conducted for the
      subjects and SPSS version 20.0 was used for data entry and analysis. Chi square
      test was carried out to determine the difference between the two groups of
      schools. RESULTS: Of the total of 359 subjects, 55.1% were from schools that do
      not implement the SFP and 44.9% were from schools that implement the SFP. The
      prevalence of stunting among children in schools on the SFP was 16.2% compared
      with 17.2% among children in schools that do not implement the SFP. The
      prevalence of thinness was two times higher (9.3%) among children in schools on
      the SFP than in children in schools that do not implement the SFP (4.6%) (p =
      0.028). The prevalence of overweight among children in schools on the SFP was
      1.9% and 0.0% for children in schools that do not implement the SFP. Sub
      district, sex, age of pupil, area of residence and community type were
      significantly associated with stunting (p = 0.002), (p = 0.008), (p = 0.008), (p
      < 0.001) and (p = 0.007) respectively. CONCLUSION: Overweight and thinness were
      higher among children in schools on SFP than in children in schools without SFP.
      An evaluation of the implementation of the school feeding programme is
      recommended for future studies.

PMID- 29329534
TI  - A large-scale study of a poultry trading network in Bangladesh: implications for
      control and surveillance of avian influenza viruses.
AB  - BACKGROUND: Since its first report in 2007, avian influenza (AI) has been endemic
      in Bangladesh. While live poultry marketing is widespread throughout the country
      and known to influence AI dissemination and persistence, trading patterns have
      not been described. The aim of this study is to assess poultry trading practices
      and features of the poultry trading networks which could promote AI spread, and
      their potential implications for disease control and surveillance. Data on
      poultry trading practices was collected from 849 poultry traders during a cross
      sectional survey in 138 live bird markets (LBMs) across 17 different districts of
      Bangladesh. The quantity and origins of traded poultry were assessed for each
      poultry type in surveyed LBMs. The network of contacts between farms and LBMs
      resulting from commercial movements of live poultry was constructed to assess its
      connectivity and to identify the key premises influencing it. RESULTS: Poultry
      trading practices varied according to the size of the LBMs and to the type of
      poultry traded. Industrial broiler chickens, the most commonly traded poultry,
      were generally sold in LBMs close to their production areas, whereas ducks and
      backyard chickens were moved over longer distances, and their transport involved
      several intermediates. The poultry trading network composed of 445 nodes (73.2%
      were LBMs) was highly connected and disassortative. However, the removal of only
      5.6% of the nodes (25 LBMs with the highest betweenness scores), reduced the
      network's connectedness, and the maximum size of output and input domains by more
      than 50%. CONCLUSIONS: Poultry types need to be discriminated in order to
      understand the way in which poultry trading networks are shaped, and the level of
      risk of disease spread that these networks may promote. Knowledge of the network
      structure could be used to target control and surveillance interventions to a
      small number of LBMs.

PMID- 29329535
TI  - Measurement of the potential geographic accessibility from call to definitive
      care for patient with acute stroke.
AB  - BACKGROUND: The World Health Organization refers to stroke, the second most
      frequent cause of death in the world, in terms of pandemic. Present treatments
      are only effective within precise time windows. Only 10% of thrombolysis patients
      are eligible. Late assessment of the patient resulting from admission and lack of
      knowledge of the symptoms is the main explanation of lack of eligibility.
      METHODS: The aim is the measurement of the time of access to treatment facilities
      for stroke victims, using ambulances (firemen ambulances or EMS ambulances) and
      private car. The method proposed analyses the potential geographic accessibility
      of stroke care infrastructure in different scenarios. The study allows better
      considering of the issues inherent to an area: difficult weather conditions,
      traffic congestion and failure to respect the distance limits of emergency
      transport. RESULTS: Depending on the scenario, access times vary considerably
      within the same commune. For example, between the first and the second scenario
      for cities in the north of Rhone county, there is a 10 min difference to the
      nearest Primary Stroke Center (PSC). For the first scenario, 90% of the
      population is 20 min away of the PSC and 96% for the second scenario. Likewise,
      depending on the modal vector (fire brigade or emergency medical service),
      overall accessibility from the emergency call to admission to a Comprehensive
      Stroke Center (CSC) can vary by as much as 15 min. CONCLUSIONS: The setting up of
      the various scenarios and modal comparison based on the calculation of overall
      accessibility makes this a new method for calculating potential access to care
      facilities. It is important to take into account the specific pathological
      features and the availability of care facilities for modelling. This method is
      innovative and recommendable for measuring accessibility in the field of health
      care. This study makes possible to highlight the patients' extension of care
      delays. Thus, this can impact the improvement of patient care and rethink the
      healthcare organization. Stroke is addressed here but it is applicable to other
      pathologies.

PMID- 29329536
TI  - Dietary flavonoid intake in older adults: how many days of dietary assessment are
      required and what is the impact of seasonality?
AB  - BACKGROUND: Within- and between-person variation in nutrient intake is well
      established, but little is known about variability in dietary flavonoid intake,
      including the effect of seasonality. METHODS: Within- and between-individual
      variability of flavonoid intake, and intake of flavonoid subclasses was examined
      in older adults (n = 79; mean age 70.1 y (range: 60y-80y)), using three separate
      4-day weighed food records (WFR) collected approximately 4 months apart. The
      effects of seasonality were also examined. Mixed-effects linear regression models
      were used to estimate within- and between-individual variance components for
      flavonoids and subclasses. The number of days of dietary assessment required for
      a high level of hypothetical accuracy was calculated from variance ratios.
      RESULTS: Within- and between-individual variability was high for flavonoid
      intake, and intake of flavonoid subclasses, with variance ratios > 1. It was
      calculated that six days of WFR data are required for total flavonoid intake, and
      between 6 and 10 days was required for flavonoid subclasses. There was no effect
      of seasonality for total flavonoid intake or intake of flavonoid subclasses, with
      the exception that flavan-3-ol and flavanone intakes which were relatively low in
      summer, and in summer and winter, respectively. CONCLUSION: While the effects of
      seasonality on total flavonoid intake may be small, within- and between
      individual variation associated with flavonoid intake assessment appears to be
      substantial across 12 days of WFR data in older adults. It is recommended that a
      minimum of 6 days of weighed food records are collected to minimise the impact of
      within- and between-individual variability on total flavonoid intake assessments
      in this population.

PMID- 29329538
TI  - Peripheral blood gene expression signatures which reflect smoking and aspirin
      exposure are associated with cardiovascular events.
AB  - BACKGROUND: Cardiovascular disease and its sequelae are major causes of global
      mortality, and better methods are needed to identify patients at risk for future
      cardiovascular events. Gene expression analysis can inform on the molecular
      underpinnings of risk factors for cardiovascular events. Smoking and aspirin have
      known opposing effects on platelet reactivity and MACE, however their effects on
      each other and on MACE are not well described. METHODS: We measured peripheral
      blood gene expression levels of ITGA2B, which is upregulated by aspirin and
      correlates with platelet reactivity on aspirin, and a 5 gene validated smoking
      gene expression score (sGES) where higher expression correlates with smoking
      status, in participants from the previously reported PREDICT trial (NCT
      00500617). The primary outcome was a composite of death, myocardial infarction,
      and stroke/TIA (MACE). We tested whether selected genes were associated with MACE
      risk using logistic regression. RESULTS: Gene expression levels were determined
      in 1581 subjects (50.5% female, mean age 60.66 +/-11.46, 18% self-reported
      smokers); 3.5% of subjects experienced MACE over 12 months follow-up. Elevated
      sGES and ITGA2B expression were each associated with MACE (odds ratios [OR] =1.16
      [95% CI 1.10-1.31] and 1.42 [95% CI 1.00-1.97], respectively; p < 0.05). ITGA2B
      expression was inversely associated with self-reported smoking status and the
      sGES (p < 0.001). A logistic regression model combining sGES and ITGA2B showed
      better performance (AIC = 474.9) in classifying MACE subjects than either alone
      (AIC = 479.1, 478.2 respectively). CONCLUSION: Gene expression levels associated
      with smoking and aspirin are independently predictive of an increased risk of
      cardiovascular events.

PMID- 29329537
TI  - The HIV-1 accessory proteins Nef and Vpu downregulate total and cell surface CD28
      in CD4+ T cells.
AB  - BACKGROUND: The HIV-1 accessory proteins Nef and Vpu alter cell surface levels of
      multiple host proteins to modify the immune response and increase viral
      persistence. Nef and Vpu can downregulate cell surface levels of the co
      stimulatory molecule CD28, however the mechanism of this function has not been
      completely elucidated. RESULTS: Here, we provide evidence that Nef and Vpu
      decrease cell surface and total cellular levels of CD28. Moreover, using
      inhibitors we implicate the cellular degradation machinery in the downregulation
      of CD28. We shed light on the mechanisms of CD28 downregulation by implicating
      the Nef LL165 and DD175 motifs in decreasing cell surface CD28 and Nef DD175 in
      decreasing total cellular CD28. Moreover, the Vpu LV64 and S52/56 motifs were
      required for cell surface CD28 downregulation, while, unlike for CD4
      downregulation, Vpu W22 was dispensable. The Vpu S52/56 motif was also critical
      for Vpu-mediated decreases in total CD28 protein level. Finally, the ability of
      Vpu to downregulate CD28 is conserved between multiple group M Vpu proteins and
      infection with viruses encoding or lacking Nef and Vpu have differential effects
      on activation upon stimulation. CONCLUSIONS: We report that Nef and Vpu
      downregulate cell surface and total cellular CD28 levels. We identified
      inhibitors and mutations within Nef and Vpu that disrupt downregulation, shedding
      light on the mechanisms utilized to downregulate CD28. The conservation and
      redundancy between the abilities of two HIV-1 proteins to downregulate CD28
      highlight the importance of this function, which may contribute to the
      development of latently infected cells.

PMID- 29329539
TI  - State-dependent domicile leaving rates in Anopheles gambiae.
AB  - BACKGROUND: Transmission of Plasmodium greatly depends on the foraging behaviour
      of its mosquito vector (Anopheles spp.). The accessibility of blood hosts and
      availability of plant sugar (i.e., nectar) sources, together with mosquito energy
      state, have been shown to modulate blood feeding (and thus biting rates) of
      anopheline mosquitoes. In this study, the influence of mosquito starvation status
      and availability of nectar on the decision of female Anopheles gambiae mosquitoes
      to leave a bed net-protected blood host was examined. METHODS: Two small-scale
      mesocosm experiments were conducted using female mosquitoes starved for 0, 24 or
      48 h, that were released inside a specially constructed hut with mesh-sealed
      exits and containing a bed net-protected human volunteer. Floral cues were
      positioned on one side of the hut or the other. Several biologically plausible
      exponential decay models were developed that characterized the emigration rates
      of mosquitoes from the huts. These varied from simple random loss to leaving
      rates dependent upon energy state and time. These model fits were evaluated by
      examining their fitted parameter estimates and comparing Akaike information
      criterion. RESULTS: Starved mosquitoes left domiciles at a higher rate than
      recently fed individuals however, there was no difference between 1- and 2-day
      starved mosquitoes. There was also no effect of floral cue placement. The best
      fitting emigration model was one based on both mosquito energy state and time
      whereas the worst fitting model was one based on the assumption of constant
      leaving rates, independent of time and energy state. CONCLUSIONS: The results
      confirm that mosquito-leaving behaviour is energy-state dependent, and provide
      some of the first evidence of state-dependent domicile emigration in An. gambiae,
      which may play a role in malarial transmission dynamics. Employment of simple,
      first-principle, mechanistic models can be very useful to our understanding of
      why and how mosquitoes leave domiciles.

PMID- 29329540
TI  - Children with albinism in African regions: their rights to 'being' and 'doing'.
AB  - BACKGROUND: Albinism is an inherited condition with a relatively high prevalence
      in populations throughout sub-Saharan Africa. People with oculocutaneous albinism
      have little or no pigment in their hair, skin and eyes; thus they are visually
      impaired and extremely sensitive to the damaging effect of the sun on their skin.
      Aside from the health implications of oculocutaneous albinism, there are also
      significant sociocultural risks. The impacts of albinism are particularly serious
      in areas that associate albinism with legend and folklore, leading to
      stigmatisation and discrimination. In regions of Africa those with albinism may
      be assaulted and sometimes killed for their body parts for use in witchcraft
      related rites or to make 'lucky' charms. There is a dearth of research on the
      psychosocial aspects of albinism and particularly on how albinism impacts on the
      everyday lives of people with albinism. DISCUSSION: There is a growing
      recognition and acceptance in Africa that people with albinism should be
      considered disabled. Thomas's social-relational model of disability proposes it
      is essential to understand both the socio-structural barriers and restrictions
      that exclude disabled people (barriers to doing); and the social processes and
      practices which can negatively affect their psycho-emotional wellbeing (barriers
      to being). In this article, we combine a social model of disability with
      discussion on human rights to address the lacuna surrounding the psychosocial and
      daily experiences of people with albinism. CONCLUSION: Through using this
      combined framework we conclude that the rights of people with albinism in some
      regions of Africa are not being enacted. Our debate highlights the need to
      develop a holistic concept of rights for children and young people with albinism
      which sees human rights as indivisible. We illuminate some of the specific ways
      in which the lives of children with albinism could be improved by addressing
      'barriers to being' and 'barriers to doing', at the heart of which requires a
      shift in attitude and action to address discrimination.

PMID- 29329541
TI  - A role for endothelial nitric oxide synthase in intestinal stem cell
      proliferation and mesenchymal colorectal cancer.
AB  - BACKGROUND: Nitric oxide (NO) has been highlighted as an important agent in
      cancer-related events. Although the inducible nitric oxide synthase (iNOS)
      isoform has received most attention, recent studies in the literature indicate
      that the endothelial isoenzyme (eNOS) can also modulate different tumor processes
      including resistance, angiogenesis, invasion, and metastasis. However, the role
      of eNOS in cancer stem cell (CSC) biology and mesenchymal tumors is unknown.
      RESULTS: Here, we show that eNOS was significantly upregulated in VilCre ERT2 Apc
      fl/+ and VilCre ERT2 Apc fl/fl mouse intestinal tissue, with intense
      immunostaining in hyperproliferative crypts. Similarly, the more invasive VilCre
      ERT2 Apc fl/+ Pten fl/+ mouse model showed an overexpression of eNOS in
      intestinal tumors whereas this isoform was not expressed in normal tissue.
      However, none of the three models showed iNOS expression. Notably, when 40 human
      colorectal tumors were classified into different clinically relevant molecular
      subtypes, high eNOS expression was found in the poor relapse-free and overall
      survival mesenchymal subtype, whereas iNOS was absent. Furthermore, Apc fl/fl
      organoids overexpressed eNOS compared with wild-type organoids and NO depletion
      with the scavenger carboxy-PTIO (c-PTIO) decreased the proliferation and the
      expression of stem-cell markers, such as Lgr5, Troy, Vav3, and Slc14a1, in these
      intestinal organoids. Moreover, specific NO depletion also decreased the
      expression of CSC-related proteins in human colorectal cancer cells such as beta
      catenin and Bmi1, impairing the CSC phenotype. To rule out the contribution of
      iNOS in this effect, we established an iNOS-knockdown colorectal cancer cell
      line. NO-depleted cells showed a decreased capacity to form tumors and c-PTIO
      treatment in vivo showed an antitumoral effect in a xenograft mouse model.
      CONCLUSION: Our data support that eNOS upregulation occurs after Apc loss,
      emerging as an unexpected potential new target in poor-prognosis mesenchymal
      colorectal tumors, where NO scavenging could represent an interesting therapeutic
      alternative to targeting the CSC subpopulation.

PMID- 29329542
TI  - Relative validity of a web-based food frequency questionnaire for Danish
      adolescents.
AB  - BACKGROUND: With increased focus on dietary intake among youth and risk of
      diseases later in life, it is of importance, prior to assessing diet-disease
      relationships, to examine the validity of the dietary assessment tool. This
      study's objective was to evaluate the relative validity of a self-administered
      web-based FFQ among Danish children aged 12 to 15 years. METHODS: From a nested
      sub-cohort within the Danish National Birth Cohort, 124 adolescents participated.
      Four weeks after completion of the FFQ, adolescents were invited to complete
      three telephone-based 24HRs; administered 4 weeks apart. Mean or median intakes
      of nutrients and food groups estimated from the FFQ were compared with the mean
      of 3x24HRs. To assess the level of ranking we calculated the proportion of
      correctly classified into the same quartile, and the proportion of misclassified
      (into the opposite quartile). Spearman's correlation coefficients and de
      attenuated coefficients were calculated to assess agreement between the FFQ and
      24HRs. RESULTS: The mean percentage of all food groups, for adolescents
      classified into the same and opposite quartile was 35 and 7.5%, respectively.
      Mean Spearman's correlation was 0.28 for food groups and 0.35 for nutrients,
      respectively. Adjustment for energy and within-person variation in the 24HRs had
      little effect on the magnitude of the correlations for food groups and nutrients.
      We found overestimation by the FFQ compared with the 24HRs for fish, fruits,
      vegetables, oils and dressing and underestimation by the FFQ for meat/poultry and
      sweets. Median intake of beverages, dairy, bread, cereals, the mean total energy
      and carbohydrate intake did not differ significantly between the two methods.
      CONCLUSION: The relative validity of the FFQ compared with the 3x24HRs showed
      that the ranking ability differed across food groups and nutrients with best
      ranking for estimated intake of dairy, fruits, and oils and dressing. Larger
      variation was observed for fish, sweets and vegetables. For nutrients, the
      ranking ability was acceptable for fatty acids and iron. When evaluating
      estimates from the FFQ among Danish adolescents these findings should be
      considered.

PMID- 29329543
TI  - STAT3-induced lncRNA HAGLROS overexpression contributes to the malignant
      progression of gastric cancer cells via mTOR signal-mediated inhibition of
      autophagy.
AB  - BACKGROUND: Long noncoding RNAs (lncRNAs) are an important class of functional
      regulators involved in human cancers development, including gastric cancer (GC).
      Studying aberrantly expressed lncRNAs may provide us with new insights into the
      occurrence and development of gastric cancer by acting as oncogenes or tumor
      suppressors. In this study, we aim to examine the expression pattern of lncRNA
      HAGLROS in GC and its clinical significance as well as its biological role in
      tumor progression. METHODS: Bioinformatics analysis and qRT-PCR were performed to
      detect the relative expression of HAGLROS in GC tissues and cell lines. Gain or
      loss of function approaches were used to investigate the biological functions of
      HAGLROS. The effect of HAGLROS on proliferation was evaluated by MTT, colony
      formation assay and nude mouse xenograft model. Wound healing and Transwell
      assays were used to study the invasion and migration of GC cells. FISH, RIP, RNA
      seq, Luciferase report assays, RNA pulldown and Western blot were fulfilled to
      measure molecular mechanisms. Results are shown as means +/- S.D. and differences
      were tested for significance using Student's t-test (two-tailed). RESULTS: We
      screened out HAGLROS, whose expression was significantly increased and correlated
      with outcomes of GC patients by publicly available lncRNAs expression profiling
      and integrating analyses. Exogenous down-regulation of HAGLROS expression
      significantly suppressed the cell proliferation, invasion and migration.
      Mechanistic investigations showed that HAGLROS was a direct target of
      transcriptional factor STAT3. Moreover, HAGLROS knockdown decreased mTOR
      expression and increased autophagy-related genes ATG9A and ATG9B expression.
      Further investigation showed that HAGLROS regulated mTOR signals in two manners.
      In the one hand, HAGLROS competitively sponged miR-100-5p to increase mTOR
      expression by antagonizing miR-100-5p-mediated mTOR mRNA inhibition. On the other
      hand, HAGLROS interacted with mTORC1 components to activate mTORC1 signaling
      pathway which was known to be an important negative signal of autophagy. Here
      activation of mTORC1 signaling pathway by HAGLROS inhibited autophagy, thereby
      promoted excessive proliferation and maintained the malignant phenotype of GC
      cells. CONCLUSION: The present study demonstrates that HAGLROS overexpression
      contributes to GC development and poor prognosis and will be a target for GC
      therapy and further develop as a potential prognostic biomarker.

PMID- 29329544
TI  - The importance of drug checking outside the context of nightlife in Slovenia.
AB  - BACKGROUND: The main purpose of the research was to evaluate the implementation
      of the drug checking service in Slovenia and to obtain the opinion of users
      included in harm reduction programmes for high-risk drug users and of drug users
      in nightlife settings on drug checking, the reasons for drug checking, and their
      attitude towards adulterants in the drugs that they use. METHODS: The two final
      unrepresentative research samples included 102 respondents from harm reduction
      programmes and 554 respondents from the online sample. The questionnaire was
      designed based on analysis of the interviews conducted with professionals from
      the programmes, who took part in the drug checking project, and based on previous
      research on drug use in nightlife. RESULTS: The main findings related to users'
      opinions on the drug checking service are that users from both samples perceive
      drug checking as a contribution to risk reduction and that they find providing
      information for them about the harmful adulterants and substances that they use
      very important. In addition, users from both samples considered accessibility of
      the drug checking service as very important and would be in favour of brief
      counselling at the collection of the drug sample. One of the salient differences
      between samples was that nightlife drug users found it more important to
      recognise substances in the drugs that they use. CONCLUSIONS: Drug users from two
      different samples attach a relatively high importance to the drug checking
      service, and they consider it to be a contribution to risk reduction. As well as
      drug users in nightlife settings, high-risk drug users also perceive the drug
      checking service to be important, which is relevant in the phase of planning drug
      checking services outside the context of nightlife and for the act of
      incorporating these services into contemporary harm reduction policy.

PMID- 29329545
TI  - Use of epidemiological and entomological tools in the control and elimination of
      malaria in Ethiopia.
AB  - Malaria is the leading public health problem in Ethiopia where over 75% of the
      land surface is at risk with varying intensities depending on altitude and
      season. Although the mortality because of malaria infection has declined much
      during the last 15-20 years, some researchers worry that this success story may
      not be sustainable. Past notable achievements in the reduction of malaria disease
      burden could be reversed in the future. To interrupt, or even to eliminate
      malaria transmission in Ethiopia, there is a need to implement a wide range of
      interventions that include insecticide-treated bed nets, indoor residual
      spraying, improved control of residual malaria transmission, and improved
      diagnostics, enhanced surveillance, and methods to deal with the emergence of
      resistance both to drugs and to insecticides. Developments during the past years
      with increasing awareness about the role of very low levels of malaria prevalence
      can sustain infections, may also demand that tools not used in the routine
      control efforts to reduce or eliminate malaria, should now be made available in
      places where malaria transmission occurs.

PMID- 29329546
TI  - Whole-genome sequencing of genotype VI Newcastle disease viruses from formalin
      fixed paraffin-embedded tissues from wild pigeons reveals continuous evolution
      and previously unrecognized genetic diversity in the U.S.
AB  - BACKGROUND: Newcastle disease viruses (NDV) are highly contagious and cause
      disease in both wild birds and poultry. A pigeon-adapted variant of genotype VI
      NDV, often termed pigeon paramyxovirus 1, is commonly isolated from columbids in
      the United States and worldwide. Complete genomic characterization of these
      genotype VI viruses circulating in wild columbids in the United States is
      limited, and due to the genetic variability of the virus, failure of rapid
      diagnostic detection has been reported. Therefore, in this study, formalin-fixed
      paraffin-embedded (FFPE) samples were subjected to next-generation sequencing
      (NGS) to identify and characterize these circulating viruses, providing valuable
      genetic information. NGS enables multiple samples to be deep-sequenced in
      parallel. When used on FFPE samples, this methodology allows for retrospective
      studies of infectious organisms. METHODS: FFPE wild pigeon tissue samples
      (kidney, liver and spleen) from 10 mortality events in the U.S. between 2010 and
      2016 were analyzed using NGS to detect and sequence NDV genomes from randomly
      amplified total RNA. Results were compared to the previously published
      immunohistochemistry (IHC) results conducted on the same samples. Additionally,
      phylogenetic analyses were conducted on the complete and partial fusion gene and
      complete genome coding sequences. RESULTS: Twenty-three out of 29 IHC-positive
      FFPE pigeon samples were identified as positive for NDV by NGS. Positive samples
      produced an average genome coverage of 99.6% and an average median depth of 199.
      A previously described sub-genotype (VIa) and a novel sub-genotype (VIn) of NDV
      were identified as the causative agent of 10 pigeon mortality events in the U.S.
      from 2010 to 2016. The distribution of these viruses from the North American
      lineages match the distribution of the Eurasian collared-doves and rock pigeons
      in the U.S. CONCLUSIONS: This work reports the first successful evolutionary
      study using deep sequencing of complete NDV genomes from FFPE samples of wild
      bird origin. There are at least two distinct U.S. lineages of genotype VI NDV
      maintained in wild pigeons that are continuously evolving independently from each
      other and have no evident epidemiological connections to viruses circulating
      abroad. These findings support the hypothesis that columbids are serving as
      reservoirs of virulent NDV in the U.S.

PMID- 29329547
TI  - Microfluidic co-culture of pancreatic tumor spheroids with stellate cells as a
      novel 3D model for investigation of stroma-mediated cell motility and drug
      resistance.
AB  - BACKGROUND: Pancreatic stellate cells (PSCs), a major component of the tumor
      microenvironment in pancreatic cancer, play roles in cancer progression as well
      as drug resistance. Culturing various cells in microfluidic (microchannel)
      devices has proven to be a useful in studying cellular interactions and drug
      sensitivity. Here we present a microchannel plate-based co-culture model that
      integrates tumor spheroids with PSCs in a three-dimensional (3D) collagen matrix
      to mimic the tumor microenvironment in vivo by recapitulating epithelial
      mesenchymal transition and chemoresistance. METHODS: A 7-channel microchannel
      plate was prepared using poly-dimethylsiloxane (PDMS) via soft lithography. PANC
      1, a human pancreatic cancer cell line, and PSCs, each within a designated
      channel of the microchannel plate, were cultured embedded in type I collagen.
      Expression of EMT-related markers and factors was analyzed using
      immunofluorescent staining or Proteome analysis. Changes in viability following
      exposure to gemcitabine and paclitaxel were measured using Live/Dead assay.
      RESULTS: PANC-1 cells formed 3D tumor spheroids within 5 days and the number of
      spheroids increased when co-cultured with PSCs. Culture conditions were optimized
      for PANC-1 cells and PSCs, and their appropriate interaction was confirmed by
      reciprocal activation shown as increased cell motility. PSCs under co-culture
      showed an increased expression of alpha-SMA. Expression of EMT-related markers,
      such as vimentin and TGF-beta, was higher in co-cultured PANC-1 spheroids
      compared to that in mono-cultured spheroids; as was the expression of many other
      EMT-related factors including TIMP1 and IL-8. Following gemcitabine exposure, no
      significant changes in survival were observed. When paclitaxel was combined with
      gemcitabine, a growth inhibitory advantage was prominent in tumor spheroids,
      which was accompanied by significant cytotoxicity in PSCs. CONCLUSIONS: We
      demonstrated that cancer cells grown as tumor spheroids in a 3D collagen matrix
      and PSCs co-cultured in sub-millimeter proximity participate in mutual
      interactions that induce EMT and drug resistance in a microchannel plate.
      Microfluidic co-culture of pancreatic tumor spheroids with PSCs may serve as a
      useful model for studying EMT and drug resistance in a clinically relevant
      manner.

PMID- 29329548
TI  - The cost of a pediatric neurocritical care program for traumatic brain injury: a
      retrospective cohort study.
AB  - BACKGROUND: Inpatient care for children with severe traumatic brain injury (sTBI)
      is expensive, with inpatient charges averaging over $70,000 per case (Hospital
      Inpatient, Children Only, National Statistics. Diagnoses- clinical classification
      software (CCS) principal diagnosis category 85 coma, stupor, and brain damage,
      and 233 intracranial injury. Diagnoses by Aggregate charges [
      https://hcupnet.ahrq.gov/#setup ]). This ranks sTBI in the top quartile of
      pediatric conditions with the greatest inpatient costs (Hospital Inpatient,
      Children Only, National Statistics. Diagnoses- clinical classification software
      (CCS) principal diagnosis category 85 coma, stupor, and brain damage, and 233
      intracranial injury. Diagnoses by Aggregate charges [
      https://hcupnet.ahrq.gov/#setup ]). The Brain Trauma Foundation developed sTBI
      intensive care guidelines in 2003, with revisions in 2012 (Kochanek, Carney, et.
      al. PCCM 3:S1-S2, 2012). These guidelines have been widely disseminated, and are
      associated with improved health outcomes (Pineda, Leonard. et. al. LN 12:45-52,
      2013), yet research on the cost of associated hospital care is limited. The
      objective of this study was to assess the costs of providing hospital care to
      sTBI patients through a guideline-based Pediatric Neurocritical Care Program
      (PNCP) implemented at St. Louis Children's Hospital, a pediatric academic medical
      center in the Midwest United States. METHODS: This is a retrospective cohort
      study. We used multi-level regression to estimate pre-/post-implementation
      effects of the PNCP program on inflation adjusted total cost of in-hospital sTBI
      care. The study population included 58 pediatric patient discharges in the pre
      PNCP implementation group (July 15, 1999 - September 17, 2005), and 59 post
      implementation patient discharges (September 18, 2005 - January 15, 2012).
      RESULTS: Implementation of the PNCP was associated with a non-significant
      difference in the cost of care between the pre- and post-implementation periods
      (ebeta = 1.028, p = 0.687). CONCLUSIONS: Implementation of the PNCP to support
      delivery of guideline-based care for children with sTBI did not change the total
      per-patient cost of in-hospital care. A key strength of this study was its use of
      hospital cost data rather than charges. Future research should consider the
      longitudinal post-hospitalization costs of this approach to sTBI care.

PMID- 29329549
TI  - Near-infrared dye marking for thoracoscopic resection of small-sized pulmonary
      nodules: comparison of percutaneous and bronchoscopic injection techniques.
AB  - BACKGROUND: Minimally invasive video-assisted thoracoscopic surgery for small
      sized pulmonary nodules is challenging, and image-guided preoperative
      localisation is required. Near-infrared indocyanine green fluorescence is capable
      of deep tissue penetration and can be distinguished regardless of the background
      colour of the lung; thus, indocyanine green has great potential for use as a near
      infrared fluorescent marker in video-assisted thoracoscopic surgery. METHODS:
      Thirty-seven patients with small-sized pulmonary nodules, who were scheduled to
      undergo video-assisted thoracoscopic wedge resection, were enrolled in this
      study. A mixture of diluted indocyanine green and iopamidol was injected into the
      lung parenchyma as a marker, using either computed tomography-guided percutaneous
      or bronchoscopic injection techniques. Indications and limitations of the
      percutaneous and bronchoscopic injection techniques for marking nodules with
      indocyanine green fluorescence were examined and compared. RESULTS: In the
      computed tomography-guided percutaneous injection group (n = 15), indocyanine
      green fluorescence was detected in 15/15 (100%) patients by near-infrared
      thoracoscopy. A small pneumothorax occurred in 3/15 (20.0%) patients, and
      subsequent marking was unsuccessful after a pneumothorax occurred. In the
      bronchoscopic injection group (n = 22), indocyanine green fluorescence was
      detected in 21/22 (95.5%) patients. In 6 patients who underwent injection marking
      at 2 different lesion sites, 5/6 (83.3%) markers were successfully detected.
      CONCLUSION: Either computed tomography-guided percutaneous or bronchoscopic
      injection techniques can be used to mark pulmonary nodules with indocyanine green
      fluorescence. Indocyanine green is a safe and easily detectable fluorescent
      marker for video-assisted thoracoscopic surgery. Furthermore, the bronchoscopic
      injection approach enables surgeons to mark multiple lesion areas with less risk
      of causing a pneumothorax. TRIAL REGISTRATION: UMIN-CTR R000027833 accepted by
      ICMJE. Registered 5 January 2013.

PMID- 29329550
TI  - Systematic quantitative analysis of H2A and H2B variants by targeted proteomics.
AB  - BACKGROUND: Histones organize DNA into chromatin through a variety of processes.
      Among them, a vast diversity of histone variants can be incorporated into
      chromatin and finely modulate its organization and functionality. Classically,
      the study of histone variants has largely relied on antibody-based assays.
      However, antibodies have a limited efficiency to discriminate between highly
      similar histone variants. RESULTS: In this study, we established a mass
      spectrometry-based analysis to address this challenge. We developed a targeted
      proteomics method, using selected reaction monitoring or parallel reaction
      monitoring, to quantify a maximum number of histone variants in a single
      multiplexed assay, even when histones are present in a crude extract. This
      strategy was developed on H2A and H2B variants, using 55 peptides corresponding
      to 25 different histone sequences, among which a few differ by a single amino
      acid. The methodology was then applied to mouse testis extracts in which almost
      all histone variants are expressed. It confirmed the abundance profiles of
      several testis-specific histones during successive stages of spermatogenesis and
      the existence of predicted H2A.L.1 isoforms. This methodology was also used to
      explore the over-expression pattern of H2A.L.1 isoforms in a mouse model of male
      infertility. CONCLUSIONS: Our results demonstrate that targeted proteomics is a
      powerful method to quantify highly similar histone variants and isoforms. The
      developed method can be easily transposed to the study of human histone variants,
      whose abundance can be deregulated in various diseases.

PMID- 29329551
TI  - Efficacy and safety of combined treatment of miniscalpel acupuncture and non
      steroidal anti-inflammatory drugs: an assessor-blinded randomized controlled
      pilot study.
AB  - BACKGROUND: Chronic neck pain is a common musculoskeletal disease during the
      lifespan of an individual. With an increase in dependence on computer technology,
      the prevalence of chronic neck pain is expected to rise and this can lead to
      socioeconomic problems. We have designed the current pilot study to evaluate the
      efficacy and safety of miniscalpel acupuncture treatment combined with non
      steroidal anti-inflammatory drugs (NSAIDs) in patients with chronic neck pain.
      METHODS: This seven-week clinical trial has been designed as an assessor-blinded,
      randomized controlled trial with three parallel arms. Thirty-six patients will be
      recruited and randomly allocated to three treatment groups: miniscalpel
      acupuncture treatment; NSAIDs; and miniscalpel acupuncture treatment combined
      with NSAIDs. Patients in the miniscalpel acupuncture and combined treatment
      groups will receive three sessions of miniscalpel acupuncture over a three-week
      period. Patients in the NSAIDs and combined treatment groups will receive
      zaltoprofen (one oral tablet, three times a day for three weeks). Primary and
      secondary outcomes will be measured at weeks 0 (baseline), 1, 2, 3 (primary end
      point), and 7 (four weeks after treatment completion) using the visual analogue
      scale and the Neck Disability Index, EuroQol 5-dimension questionnaire, and
      Patients' Global Impression of Change scale, respectively. Adverse events will
      also be recorded. DISCUSSION: This pilot study will provide a basic foundation
      for a future large-scale trial as well as information about the feasibility of
      miniscalpel acupuncture treatment combined with NSAIDs for chronic neck pain.
      TRIAL REGISTRATION: Korean Clinical Research Information Service registry,
      KCT0002258 . Registered on 9 March 2017.

PMID- 29329552
TI  - Correction to: Linkage, whole genome sequence, and biological data implicate
      variants in RAB10 in Alzheimer's disease resilience.
AB  - CORRECTION: The original version of this article [1] unfortunately contained a
      typographical error. The 'Alzheimer's Disease Neuroimaging Initiative' was
      erroneously included as 'Alzheimer's Disease Neuroimaging Initative' in the
      author list of the article.

PMID- 29329554
TI  - Correction to: Detection and full genome characterization of two beta CoV viruses
      related to Middle East respiratory syndrome from bats in Italy.
AB  - CORRECTION: After Publication of the article [1], it has been brought to our
      attention that an author's name has been spelt incorrectly. The correct spelling
      should be "Massimo Ciccozzi", but it was previously included as "Massimo
      Cicozzi". The original version has now been revised to reflect this.

PMID- 29329553
TI  - Inhibitors of the integrase-transportin-SR2 interaction block HIV nuclear import.
AB  - BACKGROUND: Combination antiretroviral therapy efficiently suppresses HIV
      replication in infected patients, transforming HIV/AIDS into a chronic disease.
      Viral resistance does develop however, especially under suboptimal treatment
      conditions such as poor adherence. As a consequence, continued exploration of
      novel targets is paramount to identify novel antivirals that do not suffer from
      cross-resistance with existing drugs. One new promising class of targets are HIV
      protein-cofactor interactions. Transportin-SR2 (TRN-SR2) is a beta-karyopherin
      that was recently identified as an HIV-1 cofactor. It has been implicated in
      nuclear import of the viral pre-integration complex and was confirmed as a direct
      binding partner of HIV-1 integrase (IN). Nevertheless, consensus on its mechanism
      of action is yet to be reached. RESULTS: Here we describe the development and use
      of an AlphaScreen-based high-throughput screening cascade for small molecule
      inhibitors of the HIV-1 IN-TRN-SR2 interaction. False positives and nonspecific
      protein-protein interaction inhibitors were eliminated through different
      counterscreens. We identified and confirmed 2 active compound series from an
      initial screen of 25,608 small molecules. These compounds significantly reduced
      nuclear import of fluorescently labeled HIV particles. CONCLUSIONS: Alphascreen
      based high-throughput screening can allow the identification of compounds
      representing a novel class of HIV inhibitors. These results corroborate the role
      of the IN-TRN-SR2 interaction in nuclear import. These compounds represent the
      first in class small molecule inhibitors of HIV-1 nuclear import.

PMID- 29329555
TI  - Exercise during and after neoadjuvant rectal cancer treatment (the EXERT trial):
      study protocol for a randomized controlled trial.
AB  - BACKGROUND: Standard treatment for locally advanced rectal cancer includes 5-6
      weeks of neoadjuvant chemoradiotherapy (NACRT) followed by total mesorectal
      excision 6-8 weeks later. NACRT improves local disease control and surgical
      outcomes but also causes side effects including fatigue, diarrhea, hand-foot
      syndrome, and physical deconditioning that may impede quality of life (QoL),
      treatment completion, treatment response, and long-term prognosis. Interventions
      to improve treatment outcomes and manage side effects that are safe, tolerable
      and low-cost are highly desirable. Exercise has been shown to improve some of
      these outcomes in other cancer patient groups but no study to date has examined
      the potential benefits (and harms) of exercise training during and after NACRT
      for rectal cancer. METHODS/DESIGN: The Exercise During and After Neoadjuvant
      Rectal Cancer Treatment (EXERT) trial is a single-center, prospective, two-armed,
      phase II randomized controlled trial designed to test the preliminary efficacy of
      exercise training in this clinical setting and to further evaluate its
      feasibility and safety. Participants will be 60 rectal cancer patients scheduled
      to receive long-course NACRT followed by total mesorectal excision. Participants
      will be randomly assigned to exercise training or usual care. Participants in the
      exercise training group will be asked to complete three supervised, high
      intensity interval training sessions/week during NACRT and >= 150 min/week of
      unsupervised, moderate-to-vigorous-intensity, continuous exercise training after
      NACRT prior to surgery. Participants in the usual care group will be asked not to
      increase their exercise from baseline. Assessments will be completed pre NACRT,
      post NACRT, and pre surgery. The primary endpoint will be cardiorespiratory
      fitness (VO2 peak) at the post-NACRT time point assessed by a graded exercise
      test. Secondary endpoints will include functional fitness assessed by the
      Senior's Fitness Test, QoL assessed by the European Organisation of Research and
      Treatment of Cancer, and symptom management assessed by the M.D. Anderson Symptom
      Inventory. Exploratory clinical endpoints will include treatment toxicities,
      treatment completion, treatment response, and surgical complications. DISCUSSION:
      If the preliminary findings of EXERT are positive, additional research will be
      warranted to confirm whether exercise is an innovative treatment to maintain QoL,
      manage side effects, and/or improve treatment outcomes in rectal cancer patients.
      TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03082495 . Registered on 9
      February, 2017.

PMID- 29329556
TI  - Cancer immunotherapy beyond immune checkpoint inhibitors.
AB  - Malignant cells have the capacity to rapidly grow exponentially and spread in
      part by suppressing, evading, and exploiting the host immune system.
      Immunotherapy is a form of oncologic treatment directed towards enhancing the
      host immune system against cancer. In recent years, manipulation of immune
      checkpoints or pathways has emerged as an important and effective form of
      immunotherapy. Agents that target cytotoxic T lymphocyte-associated molecule-4
      (CTLA-4), programmed cell death receptor-1 (PD-1), and programmed cell death
      ligand-1 (PD-L1) are the most widely studied and recognized. Immunotherapy,
      however, extends beyond immune checkpoint therapy by using new molecules such as
      chimeric monoclonal antibodies and antibody drug conjugates that target malignant
      cells and promote their destruction. Genetically modified T cells expressing
      chimeric antigen receptors are able to recognize specific antigens on cancer
      cells and subsequently activate the immune system. Native or genetically modified
      viruses with oncolytic activity are of great interest as, besides destroying
      malignant cells, they can increase anti-tumor activity in response to the release
      of new antigens and danger signals as a result of infection and tumor cell lysis.
      Vaccines are also being explored, either in the form of autologous or allogenic
      tumor peptide antigens, genetically modified dendritic cells that express tumor
      peptides, or even in the use of RNA, DNA, bacteria, or virus as vectors of
      specific tumor markers. Most of these agents are yet under development, but they
      promise to be important options to boost the host immune system to control and
      eliminate malignancy. In this review, we have provided detailed discussion of
      different forms of immunotherapy agents other than checkpoint-modifying drugs.
      The specific focus of this manuscript is to include first-in-human phase I and
      phase I/II clinical trials intended to allow the identification of those drugs
      that most likely will continue to develop and possibly join the immunotherapeutic
      arsenal in a near future.

PMID- 29329557
TI  - One-year risk of serious infection in patients treated with certolizumab pegol as
      compared with other TNF inhibitors in a real-world setting: data from a national
      U.S. rheumatoid arthritis registry.
AB  - BACKGROUND: Registry studies provide a valuable source of comparative safety data
      for tumor necrosis factor inhibitors (TNFi) used in rheumatoid arthritis (RA),
      but they are subject to channeling bias. Comparing safety outcomes without
      accounting for channeling bias can lead to inaccurate comparisons between TNFi
      prescribed at different stages of the disease. In the present study, we examined
      the incidence of serious infection and other adverse events during certolizumab
      pegol (CZP) use vs other TNFi in a U.S. RA cohort before and after using a
      methodological approach to minimize channeling bias. METHODS: Patients with RA
      enrolled in the Corrona registry, aged >= 18 years, initiating CZP or other TNFi
      (etanercept, adalimumab, golimumab, or infliximab) after May 1, 2009 (n = 6215
      initiations), were followed for <= 12 months. A propensity score (PS) model was
      used to control for baseline characteristics associated with the probability of
      receiving CZP vs other TNFi. Incidence rate ratios (IRRs) of serious infectious
      events (SIEs), malignancies, and cardiovascular events (CVEs) in the CZP group vs
      other TNFi group were calculated with 95% CIs, before and after PS matching.
      RESULTS: Patients were more likely to initiate CZP later in the course of therapy
      than those initiating other TNFi. CZP initiators (n = 975) were older and had
      longer disease duration, more active disease, and greater disability than other
      TNFi initiators (n = 5240). After PS matching, there were no clinically important
      differences between CZP (n = 952) and other TNFi (n = 952). Before PS matching,
      CZP was associated with a greater incidence of SIEs (IRR 1.53 [95% CI 1.13,
      2.05]). The risk of SIEs was not different between groups after PS matching (IRR
      1.26 [95% CI 0.84, 1.90]). The 95% CI of the IRRs for malignancies or CVEs
      included unity, regardless of PS matching, suggesting no difference in risk
      between CZP and other TNFi. CONCLUSIONS: After using PS matching to minimize
      channeling bias and compare patients with a similar likelihood of receiving CZP
      or other TNFi, the 1-year risk of SIEs, malignancies, and CVEs was not
      distinguishable between the two groups.

PMID- 29329558
TI  - Quality of life and problems associated with obturators of patients with
      maxillectomies.
AB  - BACKGROUND: Maxillary defects predispose patients to different undesirable
      effects. The aim of this study was to assess the quality of life (QoL) of
      patients with maxillary defects (acquired/congenital) wearing obturators.
      METHODS: The study comprised 30 patients aged between 16 and 78 years. Interviews
      were conducted to collect information pertaining to patients; sociodemographic,
      self-reported function of obturator using Obturator Functioning Scale (OFS), self
      evaluation of general health using Visual Analogue Scale (VAS), radiotherapy
      treatment, salivary gland removal, reconstructive surgery, neck dissection and
      length of time obturators were worn. Clinical examination included type of
      maxillectomy, Aramany classification of the defect, and evaluation of obturator
      function using the Kapur retention and stability scoring system. RESULT: Quality
      of life was affected significantly by marital status (P = 0.026). Married
      patients had better quality of life 61.3%, followed by divorced patients 38.8%,
      widowed 37.3% and the least QoL was detected in single patients 36.5%.
      Significant association between the type of maxillectomy and QoL was detected (P
      = 0.002). Retention of obturator prosthesis had a highly significant association
      with QoL (P < 0.001). Type of maxillectomy had a significant relation with
      obturator retention (P = 0.005). Stability had a significant correlation with QoL
      (P = 0.022). Obturator wearers who were treated with radiotherapy had lower QoL
      than those who were not treated with radiotherapy. CONCLUSION: Rehabilitation of
      patients with maxillary defects using obturator prosthesis is an appropriate and
      not invasive treatment modality. Results support that good obturators contribute
      to a better life quality.

PMID- 29329559
TI  - SImplification of Medications Prescribed to Long-tErm care Residents (SIMPLER):
      study protocol for a cluster randomised controlled trial.
AB  - BACKGROUND: Complex medication regimens are highly prevalent in residential aged
      care facilities (RACFs). Strategies to reduce unnecessary complexity may be
      valuable because complex medication regimens can be burdensome for residents and
      are costly in terms of nursing time. The aim of this study is to investigate
      application of a structured process to simplify medication administration in
      RACFs. METHODS: SImplification of Medications Prescribed to Long-tErm care
      Residents (SIMPLER) is a non-blinded, matched-pair, cluster randomised controlled
      trial of a single multidisciplinary intervention to simplify medication regimens.
      Trained study nurses will recruit English-speaking, permanent residents from
      eight South Australian RACFs. Medications taken by residents in the intervention
      arm will be assessed once using a structured tool (the Medication Regimen
      Simplification Guide for Residential Aged CarE) to identify opportunities to
      reduce medication regimen complexity (e.g. by administering medications at the
      same time, or through the use of longer-acting or combination formulations).
      Residents in the comparison group will receive routine care. Participants will be
      followed for up to 36 months after study entry. The primary outcome measure will
      be the total number of charted medication administration times at 4 months after
      study entry. Secondary outcome measures will include time spent administering
      medications, medication incidents, resident satisfaction, quality of life, falls,
      hospitalisation and mortality. Individual-level analyses that account for
      clustering will be undertaken to determine the impact of the intervention on the
      study outcomes. DISCUSSION: Ethical approval has been obtained from the Monash
      University Human Research Ethics Committee and the aged care provider
      organisation. Research findings will be disseminated through conference
      presentations and peer-reviewed publications. SIMPLER will enable an improved
      understanding of the burden of medication use in RACFs and quantify the impact of
      regimen simplification on a range of outcomes important to residents and care
      providers. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry,
      ACTRN12617001060336 . Retrospectively registered on 20 July 2017.

PMID- 29329562
TI  - Granular cell tumors of the tongue: fibroma or schwannoma.
AB  - BACKGROUND: Granular cell tumors are benign lesions that typically occur in the
      oral cavity, but can also be found in other sites. However, the characteristics
      of these tumors are unclear. Thus, the present study aimed to investigate the
      immunohistological characteristics of these tumors of the tongue. METHODS: Seven
      patients were treated for granular cell tumors of the tongue at our institution
      during 2003-2017. Paraffin-embedded specimens were available for all cases; thus,
      retrospective immunohistochemical analyses were performed. RESULTS: All cases
      exhibited cytoplasmic acidophilic granules in the muscle layer of the tumor. Both
      the normal nerve cells and tumor cells also stained positive for PGP9.5, NSE,
      calretinin, and GFAP. A nucleus of tumor cells was typically present in the
      margin. The PAS-positive granules were also positive for CD68 (a lysozyme
      glycoprotein marker). Various sizes of nerve fibers were observed in each tumor,
      and granular cells were observed in the nerve fibers of a representative case.
      CONCLUSIONS: Based on our immunohistological findings, granular cell tumors may
      be derived from Schwann cells, and the presence of CD68 indicates that Wallerian
      degeneration after nerve injury may be a contributor to tumor formation. Thus, a
      safe surgical margin is needed to detect the infiltrative growth of granular cell
      tumors.

PMID- 29329561
TI  - Strongyloides stercoralis and hookworm co-infection: spatial distribution and
      determinants in Preah Vihear Province, Cambodia.
AB  - BACKGROUND: Strongyloides stercoralis and hookworm are two soil-transmitted
      helminths (STH) that are highly prevalent in Cambodia. Strongyloides stercoralis
      causes long-lasting infections and significant morbidity but is largely
      neglected, while hookworm causes the highest public health burden among STH. The
      two parasites have the same infection route, i.e. skin penetration. The extent of
      co-distribution, which could result in potential high co-morbidities, is unknown
      in highly endemic settings like Cambodia. The aim of this study was to predict
      the spatial distribution of S. stercoralis-hookworm co-infection risk and to
      investigate determinants of co-infection in Preah Vihear Province, North
      Cambodia. METHODS: A cross-sectional survey was conducted in 2010 in 60 villages
      of Preah Vihear Province. Diagnosis was performed on two stool samples, using
      combined Baermann technique and Koga agar culture plate for S. stercoralis and
      Kato-Katz technique for hookworm. Bayesian multinomial geostatistical models were
      used to assess demographic, socioeconomic, and behavioural determinants of S.
      stercoralis-hookworm co-infection and to predict co-infection risk at non
      surveyed locations. RESULTS: Of the 2576 participants included in the study,
      48.6% and 49.0% were infected with S. stercoralis and hookworm, respectively;
      43.8% of the cases were co-infections. Females, preschool aged children, adults
      aged 19-49 years, and participants who reported regularly defecating in toilets,
      systematically boiling drinking water and having been treated with anthelmintic
      drugs had lower odds of co-infection. While S. stercoralis infection risk did not
      appear to be spatially structured, hookworm mono-infection and co-infection
      exhibited spatial correlation at about 20 km. Co-infection risk was positively
      associated with longer walking distances to a health centre and exhibited a small
      clustering tendency. The association was only partly explained by climatic
      variables, suggesting a role for underlying factors, such as living conditions
      and remoteness. CONCLUSIONS: Both parasites were ubiquitous in the province, with
      co-infections accounting for almost half of all cases. The high prevalence of S.
      stercoralis calls for control measures. Despite several years of school-based de
      worming programmes, hookworm infection levels remain high. Mebendazole efficacy,
      as well as coverage of and compliance to STH control programmes should be
      investigated.

PMID- 29329560
TI  - Overexpression of the double homeodomain protein DUX4c interferes with
      myofibrillogenesis and induces clustering of myonuclei.
AB  - BACKGROUND: Facioscapulohumeral muscular dystrophy (FSHD) is associated with DNA
      hypomethylation at the 4q35 D4Z4 repeat array. Both the causal gene DUX4 and its
      homolog DUX4c are induced. DUX4c is immunodetected in every myonucleus of
      proliferative cells, while DUX4 is present in only 1/1000 of myonuclei where it
      initiates a gene deregulation cascade. FSHD primary myoblasts differentiate into
      either atrophic or disorganized myotubes. DUX4 expression induces atrophic
      myotubes and associated FSHD markers. Although DUX4 silencing normalizes the FSHD
      atrophic myotube phenotype, this is not the case for the disorganized phenotype.
      DUX4c overexpression increases the proliferation rate of human TE671
      rhabdomyosarcoma cells and inhibits their differentiation, suggesting a normal
      role during muscle differentiation. METHODS: By gain- and loss-of-function
      experiments in primary human muscle cells, we studied the DUX4c impact on
      proliferation, differentiation, myotube morphology, and FSHD markers. RESULTS: In
      primary myoblasts, DUX4c overexpression increased the staining intensity of KI67
      (a proliferation marker) in adjacent cells and delayed differentiation. In
      differentiating cells, DUX4c overexpression led to the expression of some FSHD
      markers including beta-catenin and to the formation of disorganized myotubes
      presenting large clusters of nuclei and cytoskeletal defects. These were more
      severe when DUX4c was expressed before the cytoskeleton reorganized and
      myofibrils assembled. In addition, endogenous DUX4c was detected at a higher
      level in FSHD myotubes presenting abnormal clusters of nuclei and cytoskeletal
      disorganization. We found that the disorganized FSHD myotube phenotype could be
      rescued by silencing of DUX4c, not DUX4. CONCLUSION: Excess DUX4c could disturb
      cytoskeletal organization and nuclear distribution in FSHD myotubes. We suggest
      that DUX4c up-regulation could contribute to DUX4 toxicity in the muscle fibers
      by favoring the clustering of myonuclei and therefore facilitating DUX4 diffusion
      among them. Defining DUX4c functions in the healthy skeletal muscle should help
      to design new targeted FSHD therapy by DUX4 or DUX4c inhibition without
      suppressing DUX4c normal function.

PMID- 29329563
TI  - PM2.5-induced oxidative stress increases intercellular adhesion molecule-1
      expression in lung epithelial cells through the IL-6/AKT/STAT3/NF-kappaB
      dependent pathway.
AB  - BACKGROUND: Epidemiological studies have shown that ambient air pollution is
      closely associated with increased respiratory inflammation and decreased lung
      function. Particulate matters (PMs) are major components of air pollution that
      damages lung cells. However, the mechanisms remain to be elucidated. This study
      examines the effects of PMs on intercellular adhesion molecule-1 (ICAM-1)
      expression and the related mechanisms in vitro and in vivo. RESULT: The
      cytotoxicity, reactive oxygen species (ROS) generation, and monocyte adherence to
      A549 cells were more severely affected by treatment with O-PMs (organic solvent
      extractable fraction of SRM1649b) than with W-PMs (water-soluble fraction of
      SRM1649b). We observed a significant increase in ICAM-1 expression by O-PMs, but
      not W-PMs. O-PMs also induced the phosphorylation of AKT, p65, and STAT3.
      Pretreating A549 cells with N-acetyl cysteine (NAC), an antioxidant, attenuated O
      PMs-induced ROS generation, the phosphorylation of the mentioned kinases, and the
      expression of ICAM-1. Furthermore, an AKT inhibitor (LY294002), NF-kappaB
      inhibitor (BAY11-7082), and STAT3 inhibitor (Stattic) significantly down
      regulated O-PMs-induced ICAM-1 expression as well as the adhesion of U937 cells
      to epithelial cells. Interleukin-6 (IL-6) was the most significantly changed
      cytokine in O-PMs-treated A549 cells according to the analysis of the cytokine
      antibody array. The IL-6 receptor inhibitor tocilizumab (TCZ) and small
      interfering RNA for IL-6 significantly reduced ICAM-1 secretion and expression as
      well as the reduction of the AKT, p65, and STAT3 phosphorylation in O-PMs-treated
      A549 cells. In addition, the intratracheal instillation of PMs significantly
      increased the levels of the ICAM-1 and IL-6 in lung tissues and plasma in WT
      mice, but not in IL-6 knockout mice. Pre-administration of NAC attenuated those
      PMs-induced adverse effects in WT mice. Furthermore, patients with chronic
      obstructive pulmonary disease (COPD) had higher plasma levels of ICAM-1 and IL-6
      compared to healthy subjects. CONCLUSION: These results suggest that PMs increase
      ICAM-1 expression in pulmonary epithelial cells in vitro and in vivo through the
      IL-6/AKT/STAT3/NF-kappaB signaling pathway.

PMID- 29329564
TI  - Phytochemical analysis, antioxidant and anti-inflammatory potential of FERETIA
      APODANTHERA root bark extracts.
AB  - BACKGROUND: Inflammation has been implicated in many disorders, including cancer
      and available therapies elicit adverse effects. Plants of the family Rubiaceae
      have shown potency against inflammation. The anti-inflammatory and anti-oxidant
      potential of Feretia apodanthera was investigated in this study to evaluate its
      effectiveness. METHODS: The phytochemical, antioxidant and anti-inflammatory
      potential of root bark (n-Hexane, diethyl ether, ethanol and aqueous) extracts of
      Feretia apodanthera was investigated in this study. The extracts were subjected
      to various chemical tests for phytochemical constituents; their antioxidant
      activity was determined using in-vitro DPPH radical scavenging activity assay and
      their anti-inflammatory activity was determined using carrageenan induced paw
      oedema model. FTIR and GCMS analysis was done to determine the compounds present.
      RESULTS: Phytochemical screening of extracts revealed the presence of unsaturated
      steroids, triterpenes, cardiac glycosides, tannins, saponin and alkaloids.
      Vitamin C had a median inhibitory concentration (IC50) of 0.038 mg/ml which was
      lower than IC50 of all the extracts. Of all the extracts, ethanol extract had the
      lowest IC50 (0.044 mg/ml) which is comparable to vitamin C. Anti-inflammatory
      studies showed that the inflammation inhibition potential of 400 mg/kg body
      weight of all the extracts was significantly lower (p < 0.05) than the standard
      ketoprofen (50 mg/kg) at the first three hours but significantly higher (p <
      0.05) at the fourth hour. At the fifth hour, the inflammation inhibition
      potential of diethyl ether, ethanol and aqueous extracts were significantly
      higher (p < 0.05) than that of the standard. FTIR analysis showed the presence of
      ketones, amines, alkenes and carboxylic groups. GCMS analysis revealed compounds
      that are potential anti-inflammatory agents. CONCLUSION: This study revealed that
      extracts of Feretia apodanthera possess anti-inflammatory effects against right
      hind paw oedema of albino rats and can act as an effective antioxidant.

PMID- 29329565
TI  - Correction to: Current research into brain barriers and the delivery of
      therapeutics for neurological diseases: a report on CNS barrier congress London,
      UK, 2017.
AB  - After publication of the article [1], it has been brought to our attention that
      there are some errors in the formatting of names in the final version of the
      article.

PMID- 29329566
TI  - General and erosive tooth wear of 16-year-old adolescents in Kuantan, Malaysia:
      prevalence and association with dental caries.
AB  - BACKGROUND: The objective of this study was to determine the prevalence and
      severity of general tooth wear (GTW), i.e. tooth wear irrespective of etiology
      and erosive tooth wear (ETW), i.e. tooth wear predominantly due to erosion; and
      also to investigate the relationship between ETW and dental caries experience in
      16-year-old adolescents in Kuantan, Malaysia. METHODS: A multi-staged cluster
      sampling method was employed. A total of 598 16-year-old adolescents participated
      in this study. Participants' demographic profile was assessed through a self
      administered questionnaire. Clinical examinations were carried out under
      standardized conditions by a single examiner. The level of GTW was recorded using
      the modified Smith and Knight's Tooth Wear Index (TWI) whilst ETW were recorded
      using the Basic Erosive Wear Examination (BEWE) index. This index was developed
      to record clinical findings and assist in the decision-making process for the
      management of erosive tooth wear. Dental caries was recorded using the D3MFT
      index whereby D3 denotes obvious dental decay into dentine detected visually.
      RESULTS: The prevalence of GTW, ETW and dental caries, i.e. percentage of
      individuals found to have at least one lesion, was 99.8%, 45.0% and 27.8%
      respectively. Two thirds of affected teeth with GTW were observed to have a TWI
      score of 1 whereas almost all of the affected teeth with ETW had a BEWE score of
      2. The mean D3MFT was 0.62 (95% CI 0.50, 0.73) with Decayed (D) teeth being the
      largest component, mean D3T was 0.36 (95% CI 0.30, 0.43). There was no
      significant association between socio-demographic factors and prevalence of ETW.
      Logistic regression analysis also showed no significant relationship between the
      prevalence of ETW and D3MFT (p > 0.05). CONCLUSIONS: Almost all adolescents
      examined had GTW but they were mainly early lesions. However, nearly half were
      found to have ETW of moderate severity (BEWE score 2). No significant
      relationship between the occurrence of erosive tooth wear and caries was observed
      in this population.

PMID- 29329567
TI  - Modified Pilates as an adjunct to standard physiotherapy care for urinary
      incontinence: a mixed methods pilot for a randomised controlled trial.
AB  - BACKGROUND: Urinary incontinence (UI) is a distressing condition affecting at
      least 5 million women in England and Wales. Traditionally, physiotherapy for UI
      comprises pelvic floor muscle training, but although evidence suggests this can
      be effective it is also recognised that benefits are often compromised by patient
      motivation and commitment. In addition, there is increasing recognition that
      physical symptoms alone are poor indicators of the impact of incontinence on
      individuals' lives. Consequently, more holistic approaches to the treatment of
      UI, such as Modified Pilates (MP) have been recommended. This study aimed to
      provide preliminary findings about the effectiveness of a 6-week course of MP
      classes as an adjunct to standard physiotherapy care for UI, and to test the
      feasibility of a randomised controlled trial (RCT) design. METHODS: The study
      design was a single centre pilot RCT, plus qualitative interviews. 73 women
      referred to Women's Health Physiotherapy Services for UI at Colchester Hospital
      University NHS Foundation Trust were randomly assigned to two groups: a 6-week
      course of MP classes in addition to standard physiotherapy care (intervention) or
      standard physiotherapy care only (control). Main outcome measures were self
      reported UI, quality of life and self-esteem at baseline (T1), completion of
      treatment (T2), and 5 months after randomisation (T3). Qualitative interviews
      were conducted with a subgroup at T2 and T3. Due to the nature of the
      intervention blinding of participants, physiotherapists and researchers was not
      feasible. RESULTS: Post-intervention data revealed a range of benefits for women
      who attended MP classes and who had lower symptom severity at baseline: improved
      self-esteem (p = 0.032), decreased social embarrassment (p = 0.026) and lower
      impact on normal daily activities (p = 0.025). In contrast, women with higher
      symptom severity showed improvement in their personal relationships (p = 0.017).
      Qualitative analysis supported these findings and also indicated that MP classes
      could positively influence attitudes to exercise, diet and wellbeing.
      CONCLUSIONS: A definitive RCT is feasible but will require a large sample size to
      inform clinical practice. TRIAL REGISTRATION: ISRCTN74075972 Registered 12/12/12
      (Retrospectively registered).

PMID- 29329568
TI  - Prospective longitudinal quality of life and survival outcomes in patients with
      advanced infiltrative hepatocellular carcinoma and portal vein thrombosis treated
      with Yttrium-90 radioembolization.
AB  - BACKGROUND: To determine the effect of Yttrium-90 (Y90) radioembolization on
      health-related quality of life (HRQOL) and its effect on overall survival
      advanced, unresectable infiltrative hepatocellular carcinoma (HCC) patients with
      concurrent portal vein thrombosis (PVT). METHODS: Consecutive patients with
      unresectable infiltrative HCC and PVT were recruited. The Short-Form 36 (SF-36)
      questionnaire was used to assess HRQOL for consecutive patients treated with
      glass-based Y90 based on a prospective phase II trial. MR imaging was used to
      determine tumor progression every 3 months post-treatment. Overall survival (OS)
      from treatment and time to progression (TTP) was analyzed using Kaplan-Meier
      estimation and log-rank test. RESULTS: Thirty patients were treated and followed
      for 17.4 months; physical and mental component summary scores (PCS & MCS)
      remained unchanged at one, three, and six months. While no difference was
      observed in baseline SF-36 scores for patients with prolonged TTP (>=4 months)
      and OS (>= 6 months), corresponding 1-month PCS were significantly higher than
      those with TTP < 4 months and OS < 6 months. At 1 month, patients with normalized
      Physical Function (PF), Role Physical (RP) and PCS within 2 standard deviations
      (SD) of US normalized baseline scores had a significantly prolonged median OS
      (15.7 vs. 3.7 months; p < 0.001) and TTP (12.4 vs. 1.8 mo; p < 0.001) compared
      those with physical component scores greater than 2SD below normalized US
      population values. CONCLUSION: Y90 radioembolization for HCC demonstrated long
      term preservation of HRQOL. Lower baseline HRQOL scores were predictive of poorer
      OS. Early (1 month post-treatment) significant decreases in PCS were independent
      predictors of poorer OS and TTP. TRIAL REGISTRATION: ClinicalTrials.gov
      identifier NCT01556282 , registered March 16, 2012.

PMID- 29329569
TI  - Effect of total number of harvested lymph nodes on survival outcomes after
      curative resection for gastric adenocarcinoma: findings from an eastern high
      volume gastric cancer center.
AB  - BACKGROUND: Greater lymph node retrieval in gastric cancer improves staging
      accuracy and may improve survival from increased clearance of nodal
      micrometastasis. This retrospective cohort study investigated if more lymph nodes
      removed in gastric cancer increases survival and if such effect is stage-specific
      due to differential risks of nodal micrometastasis and systemic disease. METHODS:
      The prospectively collected database of curatively resected gastric cancer
      patients in National Cancer Center, South Korea between 2000 and 2009 was
      reviewed. Disease-free survival (DFS) and overall survival (OS) for all patients
      and for each stage according to number of lymph nodes examined (1-30, 31-45, >
      45) were analyzed. RESULTS: Of 4049 patients, 96.6% and 98.4% underwent D2
      (perigastric and extragastric) lymphadenectomy and had >= 15 lymph nodes
      examined. Mean number of nodes examined was 43. Five-year OS & DFS rates were
      83.3% and 80.7%. Patients with > 45 nodes examined had significantly lower DFS (p
      = 0.002) and OS (p = 0.007) compared to those with 1-30 and 31-45 nodes. However,
      proportion of patients with > 45 nodes examined increased with stage (p =
      0.0005). Per stage, there was no significant difference in DFS and OS according
      to number of nodes examined except for stage IIIA favoring more nodes (p = 0.018
      and p = 0.044, respectively). Similar trend was seen in stage IIB. Number of
      examined nodes positively correlated with number of pathologic nodes for all
      patients (r = 0.144, p < .001) but not for stage IIB and IIIA. Number of nodes
      examined was a significant survival predictor in stage IIIA. CONCLUSION: Greater
      lymph node harvest showed improved survival in intermediate-stage gastric cancer.

PMID- 29329570
TI  - Exophthalmos in a young woman with no graves' disease - a case report of IgG4
      related orbitopathy.
AB  - BACKGROUND: Immunoglobulin G4-related disease (IgG4-rd) is characterized by
      lymphoplasmacytic infiltration and tissue fibrosis. Orbital manifestations of
      IgG4-rd may include unilateral or bilateral proptosis, cicatricial extraocular
      muscle myopathy, orbital inflammation and pain which may mimic ophthalmic Graves'
      disease. CASE PRESENTATION: A 25-year-old woman has been referred to the
      endocrinology clinic, 4 months after delivery, with suspected Graves'
      orbitopathy. She has had bronchial asthma and recurrent skin rashes of unknown
      aetiology for the last 10 years and was treated for dacryoadenitis with steroid
      containing eye drops 5 years ago. During pregnancy she developed eyelid swelling.
      After delivery, eyelid redness and retrobulbar pain evolved. Proptosis was
      demonstrated by Hertel's exophthalmometry. Orbital magnetic resonance imaging
      showed enlarged lateral and superior rectus muscles in both orbits. Thyroid
      function tests were in the normal range and no thyroid stimulating hormone (TSH)
      receptor autoantibodies were present. The eye muscle involvement pattern raised
      suspicion, and the high IgG4 level with positive histology of the lacrimal gland
      confirmed the diagnosis of immunoglobulin G4-related orbitopathy. Rapid
      improvement was observed following oral methylprednisolone. CONCLUSIONS: IgG4
      related orbitopathy may mimic Graves' orbitopathy. Euthyroid patients with no TSH
      receptor autoantibodies should be evaluated for immunoglobulin G4-related
      orbitopathy. Once IgG4-related orbitopathy is proven, other manifestations of
      IgG4-related disease have to be searched for; lifelong follow-up is warranted.

PMID- 29329571
TI  - Environmental exposures and fetal growth: the Haifa pregnancy cohort study.
AB  - BACKGROUND: The developing fetus is susceptible to environmental insults.
      Studying the effects of environmental exposures on fetal growth is essential for
      understanding the causal pathway between prenatal exposures and pregnancy
      outcomes. Here we describe the Haifa Pregnancy Cohort Study (HPCS) and discuss
      challenges and opportunities in applying "big data" paradigm. METHODS: Maccabi
      Healthcare Services (MHS), is the second largest Israeli health maintenance
      organization (HMO) providing care services to two million beneficiaries. The HPCS
      cohort potentially includes ~750,000 newborns born between 1998 and 2017. We will
      estimate daily exposures to air pollutants, temperature and greenness, using
      satellite-based data and models. We hypothesize that residents of Haifa have
      higher exposures to environmental pollutants and that in pregnant women this
      higher exposure is associated with poorer fetal growth. We will evaluate outcomes
      such as birth-weight, head-circumference and gestational age at birth. We will
      adjust for pregnancy complications such as pre-eclampsia and gestational diabetes
      and parental variables, such as maternal weight, age and smoking habits as
      potential confounders. In addition, we will conduct a multi-tiered field study,
      nested within this population, among 150 pregnant women residing in two
      geographical regions-one in the polluted Haifa area, and one in a relatively
      unpolluted area in central Israel. Blood and urinary samples will be collected,
      as well as personal and indoor exposure to air pollution. DISCUSSION: Evaluating
      environmental exposures of pregnant women and assessing in utero growth over the
      course of the pregnancy during different exposure windows, is of great scientific
      and public health interest. Recent advances in data collection and analysis pose
      great promise to provide insights into contribution of environment to the health
      of the developing fetus, but also pose major challenges and pitfalls, such as
      data management, proper statistical framework and integration of data in the
      population-based study and selectiveness in the nested field study. Yet the
      continuing follow-up of the study cohort, integrating data from different
      services, health-promotion, and eventually, application later in real life of our
      main promises. Our study aims to meet these challenges and to provide evidence of
      the environmental exposures associated with fetal growth.

PMID- 29329572
TI  - Socio-demographic and lifestyle determinants of dietary patterns in French
      speaking Switzerland, 2009-2012.
AB  - BACKGROUND: Food intake is a complex behaviour which can be assessed using
      dietary patterns. Our aim was to characterize dietary patterns and associated
      factors in French-speaking Switzerland. METHODS: Cross-sectional study conducted
      between 2009 and 2012 in the city of Lausanne, Switzerland, including 4372
      participants (54% women, 57.3 +/- 10.3 years). Food consumption was assessed
      using a validated food frequency questionnaire. Dietary patterns were assessed by
      principal components analysis. RESULTS: Three patterns were identified: "Meat &
      fries"; "Fruits & Vegetables" and "Fatty & sugary". The "Meat & fries" pattern
      showed the strongest correlations with total and animal protein and cholesterol
      carbohydrates, dietary fibre and calcium. The "Fruits & Vegetables" pattern
      showed the strongest correlations with dietary fibre, carotene and vitamin D. The
      "Fatty & sugary" pattern showed the strongest correlations with total energy and
      saturated fat. On multivariate analysis, male gender, low educational level and
      sedentary status were positively associated with the "Meat & fries" and the
      "Fatty & sugary" patterns, and negatively associated with the "Fruits &
      Vegetables" pattern. Increasing age was inversely associated with the "Meat &
      fries" pattern; smoking status was inversely associated with the "Fruits &
      Vegetables" pattern. Being born in Portugal or Spain was positively associated
      with the "Meat & fries" and the "Fruits & Vegetables" patterns. Increasing body
      mass index was positively associated with the "Meat & fries" pattern and
      inversely associated with the "Fatty & sugary" pattern. CONCLUSIONS: Three
      dietary patterns, one healthy and two unhealthy, were identified in the Swiss
      population. Several associated modifiable behaviours were identified; the
      information on socio- demographic determinants allows targeting of the most
      vulnerable groups in the context of public health interventions.

PMID- 29329573
TI  - Female genital mutilation/cutting in Italy: an enhanced estimation for first
      generation migrant women based on 2016 survey data.
AB  - BACKGROUND: Migration flows of women from Female Genital Mutilation/Cutting
      practicing countries have generated a need for data on women potentially affected
      by Female Genital Mutilation/Cutting. This paper presents enhanced estimates for
      foreign-born women and asylum seekers in Italy in 2016, with the aim of
      supporting resource planning and policy making, and advancing the methodological
      debate on estimation methods. METHODS: The estimates build on the most recent
      methodological development in Female Genital Mutilation/Cutting direct and
      indirect estimation for Female Genital Mutilation/Cutting non-practicing
      countries. Direct estimation of prevalence was performed for 9 communities using
      the results of the survey FGM-Prev, held in Italy in 2016. Prevalence for
      communities not involved in the FGM-Prev survey was estimated using to the
      'extrapolation-of-FGM/C countries prevalence data method' with corrections
      according to the selection hypothesis. RESULTS: It is estimated that 60 to 80
      thousand foreign-born women aged 15 and over with Female Genital
      Mutilation/Cutting are present in Italy in 2016. We also estimated the presence
      of around 11 to 13 thousand cut women aged 15 and over among asylum seekers to
      Italy in 2014-2016. Due to the long established presence of female migrants from
      some practicing communities Female Genital Mutilation/Cutting is emerging as an
      issue also among women aged 60 and over from selected communities. Female Genital
      Mutilation/Cutting is an additional source of concern for slightly more than 60%
      of women seeking asylum. CONCLUSIONS: Reliable estimates on Female Genital
      Mutilation/Cutting at country level are important for evidence-based policy
      making and service planning. This study suggests that indirect estimations cannot
      fully replace direct estimations, even if corrections for migrant socioeconomic
      selection can be implemented to reduce the bias.

PMID- 29329574
TI  - Microcephaly epidemic related to the Zika virus and living conditions in Recife,
      Northeast Brazil.
AB  - BACKGROUND: Starting in August 2015, there was an increase in the number of cases
      of neonatal microcephaly in Northeast Brazil. These findings were identified as
      being an epidemic of microcephaly related to Zika virus (ZIKV) infection. The
      present study aims to analyse the spatial distribution of microcephaly cases in
      Recife (2015-2016), which is in Northeast Brazil, and its association with the
      living conditions in this city. METHODS: This was an ecological study that used
      data from reported cases of microcephaly from the State Health Department of
      Pernambuco (August 2015 to July 2016). The basic spatial unit of analysis was the
      94 districts of Recife. The case definition of microcephaly was: neonates with a
      head circumference of less than the cut-off point of -2 standard deviations below
      the mean value from the established Fenton growth curve. As an indicator of the
      living conditions of the 94 districts, the percentage of heads of households with
      an income of less than twice the minimum wage was calculated. The districts were
      classified into four homogeneous strata using the K-means clustering algorithm.
      We plotted the locations of each microcephaly case over a layer of living
      conditions. RESULTS: During the study period, 347 microcephaly cases were
      reported, of which 142 (40.9%) fulfilled the definition of a microcephaly case.
      Stratification of the 94 districts resulted in the identification of four strata.
      The highest stratum in relation to the living conditions presented the lowest
      prevalence rate of microcephaly, and the overall difference between this rate and
      the rates of the other strata was statistically significant. The results of the
      Kruskal-Wallis test demonstrated that there was a strong association between a
      higher prevalence of microcephaly and poor living conditions. After the first 6
      months of the study period, there were no microcephaly cases recorded within the
      population living in the richest socio-economic strata. CONCLUSION: This study
      showed that those residing in areas with precarious living conditions had a
      higher prevalence of microcephaly compared with populations with better living
      conditions.

PMID- 29329575
TI  - MicroRNA-200a confers chemoresistance by antagonizing TP53INP1 and YAP1 in human
      breast cancer.
AB  - BACKGROUND: Emerging evidence suggests molecular and phenotypic association
      between treatment resistance and epithelial-mesenchymal transition (EMT) in
      cancer. Compared with the well-defined molecular events of miR-200a in EMT, the
      role of miR-200a in therapy resistance remains to be elucidated. METHODS: Breast
      cancer cells transfected with mimic or inhibitor for miR-200a was assayed for
      chemoresistance in vitro. miR-200a expression was assessed by quantitative real
      time PCR (qRT-PCR) in breast cancer patients treated with preoperative
      chemotherapy. Luciferase assays, cell proliferation assay were performed to
      identify the targets of miR-200a and the mechanism by which it promotes treatment
      resistance. Survival analysis was used to evaluate the prognosis value of miR
      200a. RESULTS: In this study, our results showed ectopic expression of miR-200a
      promotes chemoresistance in breast cancer cell lines to several chemotherapeutic
      agents, whereas inhibition of miR-200a enhances gemcitabine chemosensitivity in
      resistance cancer cells. We found overexpression of miR-200a was closely
      associated with poor response to preoperative chemotherapy and poor prognosis in
      breast cancer patients. Furthermore, knockdown of YAP1 and TP53INP1 phenocopied
      the effects of miR-200a overexpression, and confirmed that TP53INP1 is a novel
      target of miR-200a. Remarkably, TP53INP1 expression is inversely correlated with
      miR-200a expression in Breast cancer cell lines. Taken together, these clinical
      and experimental results demonstrate that miR-200a is a determinant of
      chemoresistance of breast cancer. CONCLUSIONS: Upregulated miR-200a enhances
      treatment resistance via antagonizing TP53INP1 and YAP1 in breast cancer.

PMID- 29329576
TI  - Spontaneous prematurity in fetuses with congenital diaphragmatic hernia: a
      retrospective cohort study about prenatal predictive factors.
AB  - BACKGROUND: To evaluate possible predictive factors of spontaneous prematurity in
      fetuses with congenital diaphragmatic hernia (CDH). METHODS: A retrospective
      cohort study was performed. Inclusion criteria were presence of CDH; absence of
      fetoscopy; absence of karyotype abnormality; maximum of one major malformation
      associated with diaphragmatic hernia; ultrasound monitoring at the Obstetrics
      Clinic of Clinicas Hospital at the University of Sao Paulo School of Medicine,
      from January 2001 to October 2014. The data were obtained through the electronic
      records and ultrasound system of our fetal medicine service. The following
      variables were analyzed: maternal age, primiparity, associated maternal diseases,
      smoking, previous spontaneous preterm birth, fetal malformation associated with
      hernia, polyhydramnios, fetal growth restriction, presence of intrathoracic
      liver, invasive procedures performed, side of hernia and observed-to- expected
      lung to head ratio (o/e LHR). On individual analysis, variables were assessed
      using the Chi-square test and the Mann-Whitney test. A multiple logistic
      regression model was applied to select variables independently influencing the
      prediction of preterm delivery. A ROC curve was constructed with the significant
      variable, identifying the values with best sensitivity and specificity to be
      suggested for use in clinical practice. RESULTS: Eighty fetuses were evaluated,
      of which, 21 (26.25%) were premature. O/e LHR was the only factor associated with
      prematurity (p = 0.020). The ROC curve showed 93% sensitivity with 48.4%
      specificity for the cutoff of 40%. CONCLUSION: O/e LHR was the only predictor of
      prematurity in this sample.

PMID- 29329577
TI  - Respiratory explants as a model to investigate early events of contagious bovine
      pleuropneumonia infection.
AB  - Contagious bovine pleuropneumonia (CBPP) is a severe disease caused by Mycoplasma
      mycoides subsp. mycoides (Mmm). Knowledge on CBPP pathogenesis is fragmented and
      hampered by the limited availability of laboratory animal and in vitro models of
      investigation. The purpose of the present study is to assess respiratory explants
      as useful tools to study the early stages of CBPP. Explants were obtained from
      trachea, bronchi and lungs of slaughtered cattle, tested negative for Mycoplasma
      spp. and for the major bacterial and viral respiratory pathogens. The interaction
      of Mmm with explant cells was studied by immunohistochemistry (IHC), double
      labelling indirect immunofluorescence (DLIIF) and laser scanning confocal
      microscopy (LSCM). Mmm capability to survive and proliferate within the explants
      was evaluated by standard microbiological procedures. Finally, the putative
      cellular internalization of Mmm was further investigated by the gentamicin
      invasion assay. IHC and DLIIF indicated that Mmm can colonize explants, showing a
      marked tropism for lower airways. Specifically, Mmm was detected on/inside the
      bronchiolar and alveolar epithelial cells, the alveolar macrophages and the
      endothelial cells. The interaction between Mmm and explant cells was abolished by
      the pre-incubation of the pathogen with bovine anti-Mmm immune sera. Mmm was able
      to survive and proliferate in all tracheal, bronchial and lung explants, during
      the entire time course of the experiments. LSCM and gentamicin invasion assay
      both confirmed that Mmm can enter non-phagocytic host cells. Taken together, our
      data supports bovine respiratory explants as a promising tool to investigate
      CBPP, alternative to cattle experimental infection.

PMID- 29329578
TI  - Guideline-based quality indicators-a systematic comparison of German and
      international clinical practice guidelines: protocol for a systematic review.
AB  - BACKGROUND: Quality indicators (QIs) are used in assessing the quality of
      healthcare. Evidence-based clinical practice guidelines (CPGs) are relevant
      sources for generating QIs. In this context, QIs are important tools to assess
      the implementation of guideline recommendations. However, the methodological
      approaches to guideline-based QI development vary considerably. In Germany, the
      guideline classification scheme of the AWMF (German Association of the Scientific
      Medical Societies) differentiates between S1-, S2k-, S2e-, and S3-CPGs depending
      on the methodological approach. Thus, S3-CPGs are consensus- and evidence-based
      CPGs and have the highest methodological standard in Germany. An analysis of the
      status quo of reported QIs in S3-CPGs found 35 current S3-CPGs, which report 372
      different QIs. Currently, there is no gold standard for the development of
      guideline-based QIs. To our knowledge, no studies have investigated to what
      extent guideline-based QIs from different CPGs that are related to the same topic
      are consistent. The objective of this study is to compare guideline-based QIs and
      their underlying methodological approaches of German S3-CPGs with those of topic
      related international CPGs. METHODS: Based on the previous identified German S3
      CPGs (n = 35), which report quality indicators, we will conduct systematic
      searches in the guidelines databases of G-I-N (Guidelines International Network)
      and NGC (National Guideline Clearinghouse) to identify international CPGs
      matching the topics of the S3-CPGs. If necessary, we will search additionally the
      websites of the particular CPG providers for separate documents with regard to
      QIs. We will include evidence-based CPGs which report QIs. Reported QIs as well
      as methods of development and the rationale for QIs will be extracted and
      compared with those of the S3-CPGs. DISCUSSION: This study will be part of the
      project "Systematic analysis of the translation of guideline recommendations into
      quality indicators and development of an evidence- and consensus-based standard,"
      supported by the German Research Association (DFG). The results of this analysis
      will feed into a subsequent qualitative study, which will consist of structured
      interviews with developers of international CPGs. Further, the results will be
      considered in a consensus study on standards of the translation of guideline
      recommendations into quality indicators in Germany.

PMID- 29329579
TI  - Prevalence and incidence of major depressive disorders among people living with
      HIV residing in Africa: a systematic review and meta-analysis protocol.
AB  - BACKGROUND: Depression represents one of the most frequent neuro-psychiatric
      diseases; it seems to be more prevalent in people living with HIV compared to the
      general population. However, summarized data in the African setting on the topic
      are scarce. This systematic review and meta-analysis aims at assessing the
      prevalence and incidence of major depressive disorders (MDD) in HIV-infected
      African populations residing in Africa. METHODS AND DESIGN: This review will
      include observational studies conducted among HIV-infected people residing in
      Africa, which have reported either the prevalence or incidence of MDD or enough
      data for its appraisal. Relevant records will be searched using PubMed/Medline,
      EMBASE, African Journals Online, and Africa Index Medicus. In addition, reference
      lists of eligible papers and relevant review articles will be screened. Published
      studies from inception Jan 1, 2000 to Dec 31, 2017 will be considered regardless
      of language of publication. Two review authors will independently screen, select
      studies, and extract data, with discrepancies resolved by consensus or
      arbitration by a third review author. Methodological quality of included studies
      will be assessed using the scale developed by Hoy and colleagues. Funnel-plots
      and Egger's test will be used to determine publication bias. The study-specific
      estimates will be pooled through a random-effects meta-analysis model to obtain
      an overall summary estimate. The heterogeneity will be evaluated by the chi2 test
      on Cochrane's Q statistic. Results will be presented by geographical region and
      antiretroviral therapy status. DISCUSSION: This study is based on published data;
      therefore, ethical approval is not a requirement. The final report of this study
      in the form of a scientific paper will be published in a peer-reviewed journal
      and presented at scientific conferences. This review will help to have an
      overview of the burden of MDD among HIV-infected people residing in Africa.
      SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42017058118 .

PMID- 29329580
TI  - Evidence for the activation of pyroptotic and apoptotic pathways in RPE cells
      associated with NLRP3 inflammasome in the rodent eye.
AB  - BACKGROUND: Age-related macular degeneration (AMD) is a devastating eye disease
      causing irreversible vision loss in the elderly. Retinal pigment epithelium
      (RPE), the primary cell type that is afflicted in AMD, undergoes programmed cell
      death in the late stages of the disease. However, the exact mechanisms for RPE
      degeneration in AMD are still unresolved. The prevailing theories consider that
      each cell death pathway works independently and without regulation of each other.
      Building upon our previous work in which we induced a short burst of inflammasome
      activity in vivo, we now investigate the effects of prolonged inflammasome
      activity on RPE cell death mechanisms in rats. METHODS: Long-Evans rats received
      three intravitreal injections of amyloid beta (Abeta), once every 4 days, and
      were sacrificed at day 14. The vitreous samples were collected to assess the
      levels of secreted cytokines. The inflammasome activity was evaluated by both
      immunohistochemistry and western blot. The types of RPE cell death mechanisms
      were determined using specific cell death markers and morphological
      characterizations. RESULTS: We found robust inflammasome activation evident by
      enhanced caspase-1 immunoreactivity, augmented NF-kappaB nuclear
      translocalization, increased IL-1beta vitreal secretion, and IL-18 protein
      levels. Moreover, we observed elevated proteolytic cleavage of caspase-3 and
      gasdermin D, markers for apoptosis and pyroptosis, respectively, in RPE-choroid
      tissues. There was also a significant reduction in the anti-apoptotic factor, X
      linked inhibitor of apoptosis protein, consistent with the overall changes of RPE
      cells. Morphological analysis showed phenotypic characteristics of pyroptosis
      including RPE cell swelling. CONCLUSIONS: Our data suggest that two cell death
      pathways, pyroptosis and apoptosis, were activated in RPE cells after exposure to
      prolonged inflammasome activation, induced by a drusen component, Abeta. The
      involvement of two distinct cell death pathways in RPE sheds light on the
      potential interplay between these pathways and provides insights on the future
      development of therapeutic strategies for AMD.

PMID- 29329581
TI  - MicroRNA-124 regulates the expression of MEKK3 in the inflammatory pathogenesis
      of Parkinson's disease.
AB  - BACKGROUND: Parkinson's disease (PD) is the most prevalent neurodegenerative
      disorder that is characterised by selective loss of midbrain dopaminergic (DA)
      neurons. Chronic inflammation of the central nervous system is mediated by
      microglial cells and plays a critical role in the pathological progression of PD.
      Brain-specific microRNA-124 (miR-124) expression is significantly downregulated
      in lipopolysaccharide (LPS)-treated BV2 cells and in the 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine (MPTP) model of PD. However, whether abnormal miR-124
      expression could regulate the activation of microglia remains poorly understood.
      METHODS: BV2 cells were activated by exposure to LPS, and the expression levels
      of miR-124, mitogen-activated protein kinase kinase kinase 3 (MEKK3), and the
      nuclear factor of kappaB (NF-kappaB) p-p65 were analysed. Over-expression and
      knockdown studies of miR-124 were performed to observe the effects on MEKK3/NF
      kappaB signalling pathways, and the induction of pro-inflammatory and neurotoxic
      factors was assessed. In addition, a luciferase reporter assay was conducted to
      confirm whether MEKK3 is a direct target of miR-124. Meanwhile, production of miR
      124, MEKK3, and p-p65; midbrain DA neuronal death; or activation of microglia
      were analysed when treated with or without miR-124 in the MPTP-induced model of
      PD. RESULTS: We found that the knockdown of MEKK3 could inhibit the activation of
      microglia by regulating NF-kappaB expression. Over-expression of miR-124 could
      effectively attenuate the LPS-induced expression of pro-inflammatory cytokines
      and promote the secretion of neuroprotective factors. We also first identified a
      unique role of miR-124 in mediating the microglial inflammatory response by
      targeting MEKK3/NF-kappaB signalling pathways. In the microglial culture
      supernatant (MCS) transfer model, over-expression of the miR-124 or knockdown of
      MEKK3 in BV2 cells prevented SH-SY5Y from apoptosis and death. Moreover, MEKK3
      and p-p65 were abundantly expressed in the midbrain. Furthermore, their
      expression levels increased and microglial activation was observed in the MPTP
      induced model of PD. In addition, exogenous delivery of miR-124 could suppress
      MEKK3 and p-p65 expression and attenuate the activation of microglia in the
      substantia nigra pars compacta of MPTP-treated mice. miR-124 also could prevent
      MPTP-dependent apoptotic midbrain DA cell death in a MPTP-induced PD model.
      CONCLUSIONS: Taken together, our data suggest that miR-124 can inhibit
      neuroinflammation in the development of PD by regulating the MEKK3/NF-kappaB
      signalling pathways and implicate miR-124 as a potential therapeutic target for
      regulating the inflammatory response in PD.

PMID- 29329582
TI  - When do patient reported quality of life indicators become prognostic in breast
      cancer?
AB  - BACKGROUND: Various patient reported quality-of-life indicators are independently
      prognostic for survival in metastatic breast cancer and other cancers. The same
      measures recorded at first diagnosis of early breast cancer carry no
      corresponding prognostic information. The present study aims to assess at what
      time in the disease evolution the prognostic association appears. METHODS: Among
      8024 patients enrolled in one of seven randomized controlled trials in early
      stage breast cancer 3247 had a breast cancer relapse after a median follow-up of
      12.1 years. Of these 677 had completed QL indicator assessments within defined
      windows 1, 2 or 3 months prior to relapse. We performed Cox regression analyses
      using these assessments and using identical instruments after relapse. All
      analyses were stratified by trial and adjusted for baseline clinicopathologic
      factors. RESULTS: QL indicators in the months before relapse were not
      significantly prognostic for subsequent survival with the possibly chance
      exception of mood at the second month before relapse. After relapse, physical
      well-being was statistically significantly associated with survival (P < 0.001).
      This prognostic significance increased in later post-relapse assessments. Similar
      findings were observed using patient-reported indicators for nausea and vomiting,
      appetite, coping effort, and health perception. CONCLUSIONS: Before cancer
      relapse, QL indicators were not generally prognostic for subsequent survival.
      After relapse, QL indicators substantially predicted OS, with a stronger
      association later in the course of relapsed disease. Simple patient perception of
      disease burden seems unlikely to explain this sudden change: rather the patient's
      awareness of disease relapse must contribute.

PMID- 29329583
TI  - Correction to: Dendrimer-mediated delivery of N-acetyl cysteine to microglia in a
      mouse model of Rett syndrome.
AB  - After publication of the article [1], it has been brought to our attention that
      an author's name has been formatted incorrectly.

PMID- 29329584
TI  - Validity of the school setting interview for students with special educational
      needs in regular high school - a Rasch analysis.
AB  - BACKGROUND: Participation in education is a vital component of adolescents'
      everyday life and a determinant of health and future opportunities in adult life.
      The School Setting Interview (SSI) is an instrument which assesses student
      environment fit and reflects the potential needs for adjustments to enhance
      students' participation in school activities. The aim of the study was to
      investigate the psychometric properties of the SSI for students with special
      educational needs in regular high school. METHODS: A sample of 509 students with
      special educational needs was assessed with the SSI. The polytomous unrestricted
      Rasch model was used to analyze the psychometric properties of the SSI regarding
      targeting, model fit, differential item functioning (DIF), response category
      functioning and unidimensionality. RESULTS: The SSI generally confirmed fit to
      assumptions of the Rasch model. Reliability was acceptable (0.73) and the SSI
      scale was able to separate students into three different levels of student
      environment fit. DIF among gender was detected in item "Remember things" and in
      item "Homework" DIF was detected among students with or without diagnosis. All
      items had disordered thresholds. The SSI demonstrated unidimensionality and no
      response dependence was present among items. CONCLUSION: The results suggest that
      the SSI is valid for use among students with special educational needs in order
      to provide and evaluate environmental adjustments. However, the items with the
      detected DIF and the SSI rating scale with its disordered thresholds needs to be
      further scrutinized.

PMID- 29329585
TI  - Involvement of hedgehog pathway in early onset, aggressive molecular subtypes and
      metastatic potential of breast cancer.
AB  - BACKGROUND: Dysregulation of hedgehog pathway is observed in numerous cancers.
      Relevance of hedgehog pathway genes in cancer cohort and inhibition of its
      downstream effector (GLI1) towards metastasis in cell lines are explored in the
      study. METHOD: One hundred fifty fresh tumours of breast cancer patients were
      collected for the study. Based on differential expression, panel of 6 key
      regulators of the pathway (SHH, DHH, IHH, PTCH1, SMO and GLI1) in microarray
      datasets were identified. Expressional profiles of aforementioned genes were
      later correlated with clinico-pathological parameters in Pakistani breast cancer
      cohort at transcript and protein levels. In addition, GLI1 over expressing breast
      cancer cell lines (MDA-MB-231 and MCF-7) were treated with GANT61 to explore its
      probable effects on metastasis. RESULT: SHH, DHH, PTCH1 and GLI1 were
      significantly over-expressed in tumours as compared with respective normal
      mammary tissues. A significant correlation of SHH, DHH and GLI1 expression with
      advanced tumour size, stages, grades, nodal involvement and distant metastasis
      was observed (p < 0.05). Over-expression of SHH, DHH and GLI1 was significantly
      related with patients having early onset and pre-menopausal status. Of note,
      hedgehog pathway was frequently up regulated in luminal B and triple negative
      breast cancer affected women. In addition, positive correlations were observed
      among aforementioned members of pathway and Ki67 (r-value: 0.63-0.78) emphasizing
      their role towards disease progression. Exposure of GANT61 (inhibitor for GLI1)
      significantly restricted cell proliferation, reduced cell motility and invasion.
      CONCLUSION: Role of activated hedgehog pathway in breast cancer metastasis
      provides a novel target for cancer therapy against aggressive cancer subtypes.

PMID- 29329586
TI  - IL-33/ST2 signaling contributes to radicular pain by modulating MAPK and NF
      kappaB activation and inflammatory mediator expression in the spinal cord in rat
      models of noncompressive lumber disk herniation.
AB  - BACKGROUND: Immune and inflammatory responses occurring in the spinal cord play a
      pivotal role in the progression of radicular pain caused by intervertebral disk
      herniation. Interleukin-33 (IL-33) orchestrates inflammatory responses in a wide
      range of inflammatory and autoimmune disorders of the nervous system. Thus, the
      purpose of this study is to investigate the expression of IL-33 and its receptor
      ST2 in the dorsal spinal cord and to elucidate whether the inhibition of spinal
      IL-33 expression significantly attenuates pain-related behaviors in rat models of
      noncompressive lumbar disc herniation. METHODS: Lentiviral vectors encoding short
      hairpin RNAs that target IL-33 (LV-shIL-33) were constructed for gene silencing.
      Rat models of noncompressive lumber disk herniation were established, and the
      spines of rats were injected with LV-shIL-33 (5 or 10 MUl) on the first day after
      the operation. Mechanical thresholds were evaluated during an observation period
      of 21 days. Moreover, the expression levels of spinal tumor necrosis factor-alpha
      (TNF-alpha), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and
      cyclooxygenase 2 (COX-2) and the activation of the mitogen-activated protein
      kinases (MAPK) and nuclear factor-kappaB (NF-kappaB) pathways were evaluated to
      gain insight into the mechanisms related to the contribution of IL-33/ST2
      signaling to radicular pain. RESULTS: The application of nucleus pulposus (NP) to
      the dorsal root ganglion (DRG) induced an increase in IL-33 and ST2 expression in
      the spinal cord, mainly in the dorsal horn neurons, astrocytes, and
      oligodendrocytes. Spinally delivered LV-shIL-33 knocked down the expression of IL
      33 and markedly attenuated mechanical allodynia. In addition, spinal
      administration of LV-shIL-33 reduced the overexpression of spinal IL-1beta, TNF
      alpha, and COX-2 and attenuated the activation of C-Jun N-terminal kinase (JNK),
      extracellular signal-regulated kinase (ERK), and NF-kappaB/p65 but not p38.
      CONCLUSIONS: This study indicates that spinal IL-33/ST2 signaling plays an
      important role in the development and progression of radicular pain in rat models
      of noncompressive lumber disk herniation. Thus, the inhibition of spinal IL-33
      expression may provide a potential treatment to manage radicular pain caused by
      intervertebral disk herniation.

PMID- 29329587
TI  - The effectiveness of a web 2.0 physical activity intervention in older adults - a
      randomised controlled trial.
AB  - BACKGROUND: Interactive web-based physical activity interventions using Web 2.0
      features (e.g., social networking) have the potential to improve engagement and
      effectiveness compared to static Web 1.0 interventions. However, older adults may
      engage with Web 2.0 interventions differently than younger adults. The aims of
      this study were to determine whether an interaction between intervention (Web 2.0
      and Web 1.0) and age group (<55y and >=55y) exists for website usage and to
      determine whether an interaction between intervention (Web 2.0, Web 1.0 and
      logbook) and age group (<55y and >=55y) exists for intervention effectiveness
      (changes in physical activity). METHODS: As part of the WALK 2.0 trial, 504
      Australian adults were randomly assigned to receive either a paper logbook (n =
      171), a Web 1.0 (n = 165) or a Web 2.0 (n = 168) physical activity intervention.
      Moderate to vigorous physical activity was measured using ActiGraph monitors at
      baseline 3, 12 and 18 months. Website usage statistics including time on site,
      number of log-ins and number of step entries were also recorded. Generalised
      linear and intention-to-treat linear mixed models were used to test interactions
      between intervention and age groups (<55y and >=55y) for website usage and
      moderate to vigorous physical activity changes. RESULTS: Time on site was higher
      for the Web 2.0 compared to the Web 1.0 intervention from baseline to 3 months,
      and this difference was significantly greater in the older group (OR = 1.47,
      95%CI = 1.01-2.14, p = .047). Participants in the Web 2.0 group increased their
      activity more than the logbook group at 3 months, and this difference was
      significantly greater in the older group (moderate to vigorous physical activity
      adjusted mean difference = 13.74, 95%CI = 1.08-26.40 min per day, p = .03). No
      intervention by age interactions were observed for Web 1.0 and logbook groups.
      CONCLUSIONS: Results partially support the use of Web 2.0 features to improve
      adults over 55 s' engagement in and behaviour changes from web-based physical
      activity interventions. TRIAL REGISTRATION: ACTRN ACTRN12611000157976 ,
      Registered 7 March 2011.

PMID- 29329588
TI  - Accuracy of four mononucleotide-repeat markers for the identification of DNA
      mismatch-repair deficiency in solid tumors.
AB  - BACKGROUND: To screen tumors with microsatellite instability (MSI) arising due to
      DNA mismatch repair deficiency (dMMR), a panel of five quasi-monomorphic
      mononucleotide-repeat markers amplified in a multiplex PCR (Pentaplex) are
      commonly used. In spite of its several strengths, the pentaplex assay is not
      robust at detecting the loss of MSH6-deficiency (dMSH6). In order to overcome
      this challenge, we designed this study to develop and optimize a panel of four
      quasi-monomorphic mononucleotide-repeat markers (Tetraplex) for identifying solid
      tumors with dMMR, especially dMSH6. METHODS: To improve the sensitivity for
      tumors with dMMR, we established a quasi-monomorphic variant range (QMVR) of 3-4
      bp for the four Tetraplex markers. Thereafter, to confirm the accuracy of this
      assay, we examined 317 colorectal cancer (CRC) specimens, comprising of 105 dMMR
      [45 MutL homolog (MLH)1-deficient, 45 MutS protein homolog (MSH)2-deficient, and
      15 MSH6-deficient tumors] and 212 MMR-proficient (pMMR) tumors as a test set. In
      addition, we analyzed a cohort of 138 endometrial cancers (EC) by
      immunohistochemistry to determine MMR protein expression and validation of our
      new MSI assay. RESULTS: Using the criteria of >= 1 unstable markers as MSI
      positive tumor, our assay resulted in a sensitivity of 97.1% [95% confidence
      interval (CI) = 91.9-99.0%] for dMMR, and a specificity of 95.3% (95% CI = 91.5
      97.4%) for pMMR CRC specimens. Among the 138 EC specimens, 41 were dMMR according
      to immunohistochemistry. Herein, our Tetraplex assay detected dMMR tumors with a
      sensitivity of 92.7% (95% CI = 80.6-97.5%) and a specificity of 97.9% (95% CI =
      92.8-99.4%) for pMMR tumors. With respect to tumors with dMSH6, in the CRC
      validation set, Tetraplex detected dMSH6 tumors with a sensitivity of 86.7% (13
      of 15 dMSH6 CRCs), which was subsequently validated in the EC test set as well
      (sensitivity, 75.0%; 6 of 8 dMSH6 ECs). CONCLUSIONS: Our newly optimized
      Tetraplex system will help offer a robust and highly sensitive assay for the
      identification of dMMR in solid tumors.

PMID- 29329589
TI  - Enhanced metastatic capacity of breast cancer cells after interaction and hybrid
      formation with mesenchymal stroma/stem cells (MSC).
AB  - BACKGROUND: Fusion of breast cancer cells with tumor-associated populations of
      the microenvironment including mesenchymal stroma/stem-like cells (MSC)
      represents a rare event in cell communication whereby the metastatic capacity of
      those hybrid cells remains unclear. METHODS: Functional changes were investigated
      in vitro and in vivo following spontaneous fusion and hybrid cell formation
      between primary human MSC and human MDA-MB-231 breast cancer cells. Thus,
      lentiviral eGFP-labeled MSC and breast cancer cells labeled with mcherry resulted
      in dual-fluorescing hybrid cells after co-culture. RESULTS: Double FACS sorting
      and single cell cloning revealed two different aneuploid male hybrid populations
      (MDA-hyb1 and MDA-hyb2) with different STR profiles, pronounced telomerase
      activities, and enhanced proliferative capacities as compared to the parental
      cells. Microarray-based mRNA profiling demonstrated marked regulation of genes
      involved in epithelial-mesenchymal transition and increased expression of
      metastasis-associated genes including S100A4. In vivo studies following
      subcutaneous injection of the breast cancer and the two hybrid populations
      substantiated the in vitro findings by a significantly elevated tumor growth of
      the hybrid cells. Moreover, both hybrid populations developed various distant
      organ metastases in a much shorter period of time than the parental breast cancer
      cells. CONCLUSION: Together, these data demonstrate spontaneous development of
      new tumor cell populations exhibiting different parental properties after close
      interaction and subsequent fusion of MSC with breast cancer cells. This formation
      of tumor hybrids contributes to continuously increasing tumor heterogeneity and
      elevated metastatic capacities.

PMID- 29329590
TI  - Frequent overexpression of AMAP1, an Arf6 effector in cell invasion, is
      characteristic of the MMTV-PyMT rather than the MMTV-Neu human breast cancer
      model.
AB  - BACKGROUND: The small GTPase Arf6 and its downstream effector AMAP1 (also called
      ASAP1/DDEF1) constitute a signaling pathway promoting cell invasion, in which
      AMAP1 interacts with several different proteins, including PRKD2, EPB41L5,
      paxillin, and cortactin. Components of this pathway are often overexpressed in
      human breast cancer cells, to be correlated with poor prognosis of the patients,
      whereas overexpression of the Arf6 pathway did not correlate with the four main
      molecular classes of human breast tumors. In this pathway, receptor tyrosine
      kinases, including EGFR and Her2, activate Arf6 via GEP100. MMTV-PyMT mice and
      MMTV-Neu mice are well-established models of human breast cancer, and exhibit the
      early dissemination and the lung metastasis, by utilizing protein tyrosine
      phosphorylation for oncogenesis. PyMT-tumors and Neu-tumors are known to have
      overlapping gene expression profiles, which primarily correspond to the luminal B
      type of human mammary tumors, although they differ in the time necessary for
      tumor onset and metastasis. Given the common usage of protein tyrosine
      phosphorylation, as well as the frequent use of these animal models for studying
      breast cancer at the molecular level, we here investigated whether mammary tumors
      in these mouse models utilize the Arf6-based pathway for invasion. METHODS:
      Expression levels of Arf6, AMAP1, and GEP100 were analyzed in PyMT-tumors and Neu
      tumors by western blotting. Expression of Arf6 and AMAP1 was also analyzed by
      immunohistochemistry. The involvement of AMAP1 in invasion, and the possible
      correlation of its high expression levels with cancer mesenchymal properties were
      also investigated. RESULTS: We found that PyMT-tumors, but not Neu-tumors,
      frequently overexpress AMAP1 and use it for invasion, whereas both types of
      tumors expressed Arf6 and GEP100 at different levels. High levels of the AMAP1
      expression among PyMT-tumor cells were frequently correlated with loss of the
      epithelial marker CK8 and also with expression of the mesenchymal marker vimentin
      both at the primary sites and at sites of the lung metastases. CONCLUSIONS: PyMT
      tumors appear to frequently utilize the Arf6-based invasive machinery, whereas
      Neu-tumors do not. Our results suggest that MMTV-PyMT mice, rather than MMTV-Neu
      mice, are useful to study the Arf6-based mammary tumor malignancies, as a
      representative model of human breast cancer.

PMID- 29329592
TI  - The eXtensible ontology development (XOD) principles and tool implementation to
      support ontology interoperability.
AB  - Ontologies are critical to data/metadata and knowledge standardization, sharing,
      and analysis. With hundreds of biological and biomedical ontologies developed, it
      has become critical to ensure ontology interoperability and the usage of
      interoperable ontologies for standardized data representation and integration.
      The suite of web-based Ontoanimal tools (e.g., Ontofox, Ontorat, and Ontobee)
      support different aspects of extensible ontology development. By summarizing the
      common features of Ontoanimal and other similar tools, we identified and proposed
      an "eXtensible Ontology Development" (XOD) strategy and its associated four
      principles. These XOD principles reuse existing terms and semantic relations from
      reliable ontologies, develop and apply well-established ontology design patterns
      (ODPs), and involve community efforts to support new ontology development,
      promoting standardized and interoperable data and knowledge representation and
      integration. The adoption of the XOD strategy, together with robust XOD tool
      development, will greatly support ontology interoperability and robust ontology
      applications to support data to be Findable, Accessible, Interoperable and
      Reusable (i.e., FAIR).

PMID- 29329591
TI  - Prospects for chimeric antigen receptor-modified T cell therapy for solid tumors.
AB  - The potential for adoptive cell immunotherapy as a treatment against cancers has
      been demonstrated by the remarkable response in some patients with hematological
      malignancies using autologous T cells endowed with chimeric antigen receptors
      (CARs) specific for CD19. Clinical efficacy of CAR-T cell therapy for the
      treatment of solid tumors, however, is rare due to physical and biochemical
      factors. This review focuses on different aspects of multiple mechanisms of
      immunosuppression in solid tumors. We characterize the current state of CAR
      modified T cell therapy and summarize the various strategies to combat the
      immunosuppressive microenvironment of solid tumors, with the aim of promoting T
      cell cytotoxicity and enhancing tumor cell eradication.

PMID- 29329593
TI  - Targeting ectodysplasin promotor by CRISPR/dCas9-effector effectively induces the
      reprogramming of human bone marrow-derived mesenchymal stem cells into sweat
      gland-like cells.
AB  - BACKGROUND: Patients with a deep burn injury are characterized by losing the
      function of perspiration and being unable to regenerate the sweat glands. Because
      of their easy accession, multipotency, and lower immunogenicity, bone marrow
      derived mesenchymal stem cells (BM-MSCs) represent as an ideal biological source
      for cell therapy. The aim of this study was to identify whether targeting the
      promotor of ectodysplasin (EDA) by CRISPR/dCas9-effector (dCas9-E) could induce
      the BM-MSCs to differentiate into sweat gland-like cells (SGCs). METHODS:
      Activation of EDA transcription in BM-MSCs was attained by transfection of naive
      BM-MSCs with the lenti-CRISPR/dCas9-effector and single-guide RNAs (sgRNAs). The
      impact of dCas9-E BM-MSCs on the formation of SGCs and repair of burn injury was
      identified and evaluated both in vitro and in a mouse model. RESULTS: After
      transfection with sgRNA-guided dCas9-E, the BM-MSCs acquired significantly higher
      transcription and expression of EDA by doxycycline (Dox) induction. Intriguingly,
      the specific markers (CEA, CK7, CK14, and CK19) of sweat glands were also
      positive in the transfected BM-MSCs, suggesting that EDA plays a critical role in
      promoting BM-MSC differentiation into sweat glands. Furthermore, when the dCas9-E
      BM-MSCs with Dox induction were implanted into a wound in a laboratory animal
      model, iodine-starch perspiration tests revealed that the treated paws were
      positive for perspiration, while the paws treated with saline showed a negative
      manifestation. For the regulatory mechanism, the expression of downstream genes
      of NF-kappaB (Shh and cyclin D1) was also enhanced accordingly. CONCLUSIONS:
      These results suggest that EDA is a pivotal factor for sweat gland regeneration
      from BM-MSCs and may also offer a new approach for destroyed sweat glands and
      extensive deep burns.

PMID- 29329594
TI  - Modelling the structure of a ceRNA-theoretical, bipartite microRNA-mRNA
      interaction network regulating intestinal epithelial cellular pathways using R
      programming.
AB  - OBJECTIVE: We report a method using functional-molecular databases and network
      modelling to identify hypothetical mRNA-miRNA interaction networks regulating
      intestinal epithelial barrier function. The model forms a data-analysis component
      of our cell culture experiments, which produce RNA expression data from
      Nanostring Technologies nCounter(r) system. The epithelial tight-junction (TJ)
      and actin cytoskeleton interact as molecular components of the intestinal
      epithelial barrier. Upstream regulation of TJ-cytoskeleton interaction is
      effected by the Rac/Rock/Rho signaling pathway and other associated pathways
      which may be activated or suppressed by extracellular signaling from growth
      factors, hormones, and immune receptors. Pathway activations affect epithelial
      homeostasis, contributing to degradation of the epithelial barrier associated
      with osmotic dysregulation, inflammation, and tumor development. The complexity
      underlying miRNA-mRNA interaction networks represents a roadblock for prediction
      and validation of competing-endogenous RNA network function. RESULTS: We
      developed a network model to identify hypothetical co-regulatory motifs in a
      miRNA-mRNA interaction network related to epithelial function. A mRNA-miRNA
      interaction list was generated using KEGG and miRWalk2.0 databases. R-code was
      developed to quantify and visualize inherent network structures. We identified a
      sub-network with a high number of shared, targeting miRNAs, of genes associated
      with cellular proliferation and cancer, including c-MYC and Cyclin D.

PMID- 29329595
TI  - 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  - BACKGROUND: Renal fibrosis is characterized by infiltration of interstitial
      inflammatory cells and release of inflammatory mediators, activation and
      proliferation of fibroblasts, and deposition of excessive extracellular matrix
      (ECM). The aim of this study was to evaluate the effect of human umbilical cord
      derived mesenchymal stem cell (hucMSC) conditioned medium (CM) on renal
      tubulointerstitial inflammation and fibrosis. METHODS: Renal interstitial
      fibrosis was prepared in vivo using the unilateral ureteral obstruction (UUO).
      Rats were divided randomly into Sham group, Sham group with CM, UUO group, and
      UUO group with CM. The effect of hucMSC-CM on kidney injury induced by UUO was
      assessed by detecting kidney histopathology, serum creatinine (SCr), and blood
      urea nitrogen (BUN). The levels of TNF-alpha, IL-6, and IL-1beta in serum and
      kidney tissues were detected by ELISA. The expression of proteins associated with
      fibrosis and renal inflammation was investigated using immunohistochemical
      staining and western blotting. The effects of hucMSC-CM on the TGF-beta1-induced
      epithelial-mesenchymal transition (EMT) process and on inflammation in NRK-52E
      cells were investigated by immunofluorescent staining, ELISA, and western
      blotting. RESULTS: hucMSC-CM reduced extracellular matrix deposition and
      inflammatory cell infiltration as well as release of inflammatory factors in UUO
      induced renal fibrosis. Furthermore, hucMSC-CM markedly attenuated the EMT
      process and proinflammatory cytokines in rats with UUO and TGF-beta1-induced NRK
      52E cells. hucMSC-CM also inhibited the TLR4/NF-kappaB signaling pathway in vivo
      and in vitro. CONCLUSIONS: Our results suggest that hucMSC-CM has protective
      effects against UUO-induced renal fibrosis and that hucMSC-CM exhibits its anti
      inflammatory effects through inhibiting TLR4/NF-kappaB signaling pathway
      activation.

PMID- 29329596
TI  - The epidemiology of psoriatic arthritis in Israel - a population-based study.
AB  - BACKGROUND: There is limited information on the epidemiology of psoriatic
      arthritis (PsA) in general and in Middle Eastern populations in particular. The
      aims of this study were to estimate the prevalence and incidence rates of PsA and
      their temporal trends in the general population in Israel. METHODS: In this
      study, a cohort of adult patients with PsA was derived from the database of
      Clalit Health Services (CHS), Israel's largest health fund, with over 4.4 million
      members. The crude and age- and sex-standardized prevalence and incidence rates
      of PsA from 2006 to 2015 in the general population were calculated. The variation
      in PsA prevalence was assessed in relation to several demographic factors.
      RESULTS: Among the 2,931,199 individuals aged 18 years and older registered in
      the CHS database in 2015, 4490 patients had a diagnosis of PsA (322 incident
      cases), resulting in overall crude prevalence and incidence rates of 0.153% (95%
      CI 0.149%, 0.158%) and 10.9 (95% CI 9.8, 12.3) per 100,000 population,
      respectively. The reported prevalence of PsA in Israel has doubled between 2006
      and 2015 (from 0.073% to 0.153%). In contrast, the global incidence rate remained
      stable, with a gradual increase in incidence among individuals aged 51 to 70
      years. PsA is associated with Jewish ethnicity, high socioeconomic status, and
      higher body mass index. CONCLUSIONS: The prevalence and incidence of PsA in
      Israel are within the range of previous estimates from Southern European
      populations. An increase in the reported prevalence of PsA was observed over the
      past decade in the general population in Israel.

PMID- 29329597
TI  - Does cognitive behavioral therapy alter mental defeat and cognitive flexibility
      in patients with panic disorder?
AB  - OBJECTIVE: Mental defeat and cognitive flexibility have been studied as
      explanatory factors for depression and posttraumatic stress disorder. This study
      examined mental defeat and cognitive flexibility scores in patients with panic
      disorder (PD) before and after cognitive behavioral therapy (CBT), and compared
      them to those of a gender- and age-matched healthy control group. RESULTS:
      Patients with PD (n = 15) received 16 weekly individual CBT sessions, and the
      control group (n = 35) received no treatment. Patients completed the Mental
      Defeat Scale and the Cognitive Flexibility Scale before the intervention,
      following eight CBT sessions, and following 16 CBT sessions, while the control
      group did so only prior to receiving CBT (baseline). The patients' pre-CBT Mental
      Defeat and Cognitive Flexibility Scale scores were significantly higher on the
      Mental Defeat Scale and lower on the Cognitive Flexibility Scale than those of
      the control group participants were. In addition, the average Mental Defeat Scale
      scores of the patients decreased significantly, from 22.2 to 12.4, while their
      average Cognitive Flexibility Scale scores increased significantly, from 42.8 to
      49.5. These results suggest that CBT can reduce mental defeat and increase
      cognitive flexibility in patients with PD Trial registration The study was
      registered retrospectively in the national UMIN Clinical Trials Registry on June
      10, 2016 (registration ID: UMIN000022693).

PMID- 29329598
TI  - Treatment outcome of anti-angiogenesis through VEGF-pathway in the management of
      gastric cancer: a systematic review of phase II and III clinical trials.
AB  - OBJECTIVES: Advanced gastric cancer poses a therapeutic challenge worldwide. In
      randomised clinical trials, anti-VEGF has been reported as an essential agent for
      the treatment of advanced gastric cancer. This review aims at assessing the
      treatment outcome of anti-angiogenesis therapy through the VEGF pathway in the
      management of patients with advanced gastric cancer. RESULTS: During this review,
      38 clinical trials were identified. Of these, 30 clinical trials were excluded,
      leaving eight trials of phase II and III. Ramucirumab, as a second line treatment
      of advanced gastric cancer, decreases the risk of disease progression (37-52%)
      and death (19-22%). Compare ramucirumab and bevacizumab in combination with
      traditional chemotherapy; ramucirumab has shown to improve progression-free
      survival and overall survival. Apatinib tyrosine kinase inhibitor combined with
      traditional chemotherapy has shown to improve overall response rate and
      progression-free survival with marginal improvements in overall survival.
      Chemotherapy, in combination with anti-VEGF drugs, in the management of advanced
      gastric cancer significantly improves the outcome of overall response rate,
      progression-free survival and overall survival when compared to chemotherapy
      alone. Therefore, we recommend that anti-VEGF drugs are the drugs of choice in
      the management of patients with advanced gastric cancer.

PMID- 29329599
TI  - Gallbladder ascariasis in Kosovo - focus on ultrasound and conservative therapy:
      a case series.
AB  - BACKGROUND: Ascaris lumbricoides is one of the most common intestinal infections
      in developing countries, including Kosovo. In contrast to migration to the bile
      duct, migration of the worm to the gallbladder, due to the narrow and tortuous
      nature of the cystic duct, is rare. When it does occur, it incites acalculous
      cholecystitis. CASE PRESENTATIONS: This case series describes a 16-month-old
      Albanian girl, a 22-month-old Albanian girl, a 4-year-old Albanian girl, and a 10
      year-old Albanian boy. Here we report our experience with gallbladder ascariasis
      including clinical manifestations, diagnostic procedures, and treatment. Fever,
      diarrhea and vomiting, dehydration, pale appearance, and weakness were the
      manifestations of the primary disease. In all patients, a physical examination
      revealed reduced turgor and elasticity of the skin. Abdomen was at the level of
      the chest, soft, with minimal palpatory pain. The liver and spleen were not
      palpable. A laboratory examination was not specific except for eosinophilia.
      There were no pathogenic bacteria in coproculture but Ascaris was found in all
      patients. At an ultrasound examination in all cases we found single, long, linear
      echogenic structure without acoustic shadowing containing a central, longitudinal
      anechoic tube with characteristic movement within the gallbladder. Edema of the
      gallbladder wall was suggestive of associated inflammation. There were no other
      findings on adjacent structures and organs. All patients received mebendazole 100
      mg twice a day for 3 days. They also received symptomatic therapy for
      gastroenteritis. Because of elevated markers of inflammation all patients were
      treated with antibiotics, assuming acute cholecystitis, although ultrasound was
      able to confirm cholecystitis in only two of our four patients. Since the length
      of stay was dependent on the primary pathology it was 7 to 10 days. At control
      ultrasounds on 14th day, third and sixth month, all patients were free of
      ascariasis. CONCLUSIONS: Gallbladder ascariasis should be considered in all
      patients presenting with abdominal pain, distension, colic, nausea, anorexia, and
      intermittent diarrhea associated with jaundice, nausea, vomiting, fever, and
      severe radiating pain. Eosinophilia, ova, and parasites on stool examination as
      well as an anechogenic tube with characteristic movement within the bile duct
      found on abdominal ultrasound are conclusive for diagnosis. Mebendazole is an
      effective drug for the treatment. Surgical treatment is rarely needed.

PMID- 29329600
TI  - Optimal waist circumference cut-off points for predicting metabolic syndrome
      among low-income black South African adults.
AB  - OBJECTIVE: Waist circumference has been identified as one of the strongest
      predictive tool for metabolic syndrome. This study determines the optimal cut-off
      point of waist circumference for metabolic syndrome among low-income earning
      South African black population, in Eastern Cape, South Africa. The optimal waist
      circumference cut-off point was determined through receiver operating
      characteristics analysis using the maximum Youden index. RESULTS: Among men,
      waist circumference at a cut-off value of 95.25 cm yielded the highest Youden
      index of 0.773 (sensitivity = 98%, specificity = 79%, area under curve 0.893).
      For women, waist circumference of 89.45 cm yielded the highest Youden index of
      0.339 (sensitivity = 88%, specificity = 46%, area under curve 0.713). The
      prevalence of metabolic syndrome among men, women and both sexes using the new
      cut-off points were: 17.8, 20.8 and 17.7%, respectively, compared to; 15.6, 24.8
      and 21.8%, using the traditional cut-off values of 94 and 80 cm for men and
      women, respectively. The traditional waist circumference value slightly under
      estimated the prevalence of metabolic syndrome among men and over-estimated among
      women and the overall population. A specific waist circumference cut-off point
      for South African blacks is needed for correct identification of the metabolic
      state of the populace in order to develop appropriate interventions.

PMID- 29329601
TI  - Nicotiana glauca whole-genome investigation for cT-DNA study.
AB  - OBJECTIVE: Nicotiana glauca (tree tobacco) is a naturally transgenic plant,
      containing sequences acquired from Agrobacterium rhizogenes by horizontal gene
      transfer. Besides, N. glauca contains a wide profile of alkaloids of medical
      interest. DATA DESCRIPTION: We report a high-depth sequencing and de novo
      assembly of N. glauca full genome and analysis of genome elements with bacterial
      origin. The draft genome assembly is 3.2 Gb, with N50 size of 31.1 kbp.
      Comparative analysis confirmed the presence of single, previously described gT
      insertion. No evidence was acquired to support idea of multiple T-DNA insertions
      in the N. glauca genome. Our data is the first comprehensive de novo assembly of
      tree tobacco and provide valuable information for researches in pharmacological
      and in phylogenetic fields.

PMID- 29329602
TI  - Abatacept used in combination with non-methotrexate disease-modifying
      antirheumatic drugs: a descriptive analysis of data from interventional trials
      and the real-world setting.
AB  - BACKGROUND: Methotrexate (MTX) remains the anchor drug in rheumatoid arthritis
      (RA) treatment, but is poorly tolerated or contraindicated in some patients.
      There is a wealth of data supporting the use of abatacept in combination with
      MTX, but data on alternative conventional synthetic disease-modifying
      antirheumatic drug (csDMARD) combinations with abatacept are scarce. METHODS: In
      this post-hoc exploratory analysis, efficacy and safety data were extracted from
      abatacept RA studies in which combination with csDMARDs other than MTX was
      permitted: three interventional trials (ATTAIN, ASSURE, and ARRIVE) and one real
      world study (ACTION). Patients with moderate-to-severe RA received abatacept in
      combination with MTX, hydroxychloroquine, sulfasalazine, azathioprine, or
      leflunomide for 6 months to 2 years according to the study design. Change from
      baseline in physical function (Health Assessment Questionnaire-Disability Index
      (HAQ-DI); all studies) and 28-joint Disease Activity Score (C-reactive protein)
      (DAS28 (CRP); ATTAIN, ARRIVE, and ACTION), American College of Rheumatology
      response rates (ATTAIN), and safety were assessed for individual and pooled
      csDMARD combinations for each trial. A meta-analysis was also performed on pooled
      data for HAQ-DI and DAS28 (CRP) across interventional trials. RESULTS: Across all
      four studies, 731 patients received abatacept plus one non-MTX csDMARD
      (hydroxychloroquine n = 152; sulfasalazine n = 123; azathioprine n = 59; and
      leflunomide n = 397) and 2382 patients received abatacept plus MTX. Mean changes
      from baseline in HAQ-DI scores for abatacept plus MTX (all csDMARDs pooled) vs
      abatacept plus a non-MTX csDMARD were -0.54 vs -0.44 (ATTAIN), -0.43 vs -0.43
      (ASSURE), and -0.39 vs -0.36 (ARRIVE). Mean changes from baseline in DAS28 (CRP)
      and ACR response rates were also similar with abatacept plus MTX or non-MTX
      csDMARDs. Data for individual non-MTX csDMARDs (pooled across studies) and real
      world data were consistent with these findings. Rates of treatment-related
      adverse events and serious adverse events, respectively, for abatacept plus one
      non-MTX csDMARD vs abatacept plus MTX were 35.7% vs 41.7% and 2.4% vs 2.3%
      (ATTAIN), 58.0% vs 55.9% and 4.2% vs 1.7% (ASSURE), and 38.1% vs 44.3% and 0.6%
      vs 2.9% (ARRIVE). CONCLUSIONS: Abatacept in combination with non-MTX csDMARDs is
      clinically effective and well tolerated in patients with moderate-to-severe RA,
      providing similar benefits to those seen with abatacept plus MTX. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT00048581 . Registered 2 November 2002.
      ClinicalTrials.gov NCT00048932 . Registered 11 November 2002. ClinicalTrials.gov
      NCT00124982 . Registered 30 June 2005. ClinicalTrials.gov NCT02109666 .
      Registered 8 April 2014.

PMID- 29329603
TI  - Green Tobacco Sickness among Brazilian farm workers and genetic polymorphisms.
AB  - OBJECTIVE: Green Tobacco Sickness (GTS) is an occupational illness caused by
      dermal absorption of nicotine from tobacco leaves. It affects thousands of farm
      workers worldwide. Brazil is the second tobacco producer in the world; despite
      this, there are few studies on GTS among Brazilian harvesters. This study aimed
      to determine the prevalence of GTS among a population of tobacco workers from a
      producing area in northeastern Brazil and investigate whether the occurrence of
      the disease was influenced by factors such age, gender and smoking status. In
      addition, it was investigated if there was association between the onset of GTS
      and genetic polymorphisms in genes that encode some detoxification enzymes. A
      semi-structured questionnaire was used to collect demographic, behavioral and
      occupational data from the referred workers. Polymorphisms were tested through
      the Polymerase Chain Reaction technique. RESULTS: The total prevalence of GTS
      found was 56.9%, with a significant difference between genders (71.7% for women
      and 35.3% for men, p < 0.0001). No association was identified between the
      investigated polymorphisms and GTS. This study confirms the occurrence of GTS
      among tobacco harvesters in Brazil with high prevalence. The investigation
      suggests the need to take preventive measures to protect tobacco workers against
      this disease.

PMID- 29329607
TI  - The genus Liriope: Phytochemistry and pharmacology.
AB  - Liriope (Liliaceae) species have been used as folk medicines in Asian countries
      since ancient times. From Liriope plants (8 species), a total of 132 compounds
      (except polysaccharides) have been isolated and identified, including steroidal
      saponins, flavonoids, phenols, and eudesmane sesquiterpenoids. The crude extracts
      or monomeric compounds from this genus have been shown to exhibit anti-tumor,
      anti-diabetic, anti-inflammatory, and neuroprotective activities. The present
      review summarizes the results on phytochemical and biological studies on Liriope
      plants. The chemotaxonomy of this genus is also discussed.

PMID- 29329608
TI  - Polyphenols isolated from Acacia mearnsii bark with anti-inflammatory and
      carbolytic enzyme inhibitory activities.
AB  - The present study was designed to characterize the polyphenols isolated from
      Acacia mearnsii bark crude extract (B) and fractions (B1-B7) obtained by high
      speed counter-current chromatography (HSCCC) and evaluate their anti-inflammatory
      and carbolytic enzymes (alpha-glucosidase and alpha-amylase) inhibitory
      activities. Fractions B4, B5, B6, B7 (total phenolics 850.3, 983.0, 843.9, and
      572.5 mg.g-1, respectively; proanthocyanidins 75.7, 90.5, 95.0, and 44.8 mg.g-1,
      respectively) showed significant activities against reactive oxygen species
      (ROS), nitric oxide (NO) production, and expression of pro-inflammatory genes
      interleukin-1beta (IL-1beta) and inducible nitric oxide synthase (iNOS) in a
      lipopolysaccharide (LPS)-stimulated mouse macrophage cell line RAW 264.7. All the
      extracts suppressed alpha-glucosidase and alpha-amylase activities, two primary
      enzymes responsible for carbohydrate digestion. A. mearnsii bark samples
      possessed significantly stronger inhibitory effects against alpha-glucosidase
      enzyme (IC50 of 0.4-1.4 MUg.mL-1) than the pharmaceutical acarbose (IC50 141.8
      MUg.mL-1). B6 and B7 (IC50 17.6 and 11.7 MUg.mL-1, respectively) exhibited alpha
      amylase inhibitory activity as efficacious as acarbose (IC50 15.4 MUg.mL-1).
      Moreover, B extract, at 25 ug.mL-1, significantly decreased the non-mitochondrial
      oxidative burst that is often associated with inflammatory response in human
      monocytic macrophages.

PMID- 29329609
TI  - Garcinia xanthochymus extract protects PC12 cells from H2O2-induced apoptosis
      through modulation of PI3K/AKT and NRF2/HO-1 pathways.
AB  - The aim of the present study was to investigate the protective effects and
      underlying mechanisms of Garcinia xanthochymus, a perennial medicinal plant
      native to Yunnan, China, against H2O2-induced oxidative damage in rat
      pheochromacytoma PC12 cells. Preincubation of PC12 cells with fruit EtOAc
      fraction (fruit-EFr., 12.5-50 umol.L-1) of G. xanthochymus for 24 h prior to H2O2
      exposure markedly improved cell viability and increased the activities of
      antioxidant enzymes (superoxide dismutase, catalase, and heme oxygenase-1 [HO
      1]), prevented lactate dehydrogenase release and lipid peroxidation
      malondialdehyde production, attenuated the decrease of matrix metalloproteinases
      (MMP), and scavenged reactive oxygen species (ROS). Fruit-EFr. also reduced BAX
      and cytochrome C expression and improved BCL-2 expression, thereby decreasing the
      ratio of BAX to BCL-2. Fruit-EFr. activated the nuclear translocation of NRF2 to
      increase HO-1 and induced the phosphorylation of AKT. Its cytoprotective effect
      was abolished by LY294002, a specific inhibitor of PI3K. Taken together, the
      above findings suggested that fruit-EFr.of G. xanthochymus could enhance cellular
      antioxidant defense capacity, at least in part, through upregulating HO-1
      expression and activating the PI3K/AKT pathway and that it could suppress H2O2
      induced oxidative damage via PI3K/AKT and NRF2/HO-1 signaling pathways.

PMID- 29329610
TI  - Bacopa monnieri extracts prevent hydrogen peroxide-induced oxidative damage in a
      cellular model of neuroblastoma IMR32 cells.
AB  - Neurodegenerative diseases are the consequences of imbalance between the
      production of oxidative stress and its nullification by cellular defense
      mechanisms. Hydrogen peroxide (H2O2), a precursor of deleterious reactive oxygen
      species, elicits oxidative stress, resulting in severe brain injuries. Bacopa
      monnieri is well known for its nerve relaxing and memory enhancing properties.
      The present study was designed to evaluate the protective effects of extracts
      from Bacopa monnieri against H2O2 induced oxidative stress using a cellular
      model, neuroblastoma IMR32 cell line. The protective potential of methanolic,
      ethanolic, and water extracts of B. monnieri (BM-MEx, BM-EEx, and BM-WEx) was
      evaluated using MTT assay. Although, all the B. monnieri extracts were found to
      protect cells against H2O2-mediated stress but BM-MEx showed significantly
      greater protection. UPLC analysis of BM-MEx revealed various polyphenols,
      including quercetin, catechin, umbelliferone, and caffeic acid predominance.
      Further, BM-MEx was found to possess considerable greater neuroprotective
      potential in comparison to the standard polyphenols such as quercetin, catechin,
      umbelliferone, and caffeic acid. The levels of antioxidant enzymes were
      significantly elevated after the pretreatment of BM-MEx and quercetin. The
      expression levels of oxidative stress markers, such as NF200, HSP70, and
      mortalin, were significantly alleviated after the pretreatment of BM-MEx as shown
      by immunofluorescence and RT-PCR. In conclusion, the present study demonstrated
      the protective effects of BM-MEx, suggesting that it could be a candidate for the
      development of neuropathological therapeutics.

PMID- 29329611
TI  - Early intervention with Didang decoction delays macrovascular lesions in diabetic
      rats through regulating AMP-activated protein kinase signaling pathway.
AB  - The study aimed to investigate the intervening role of Didang decoction (DDD) at
      different times in macrovascular endothelial defense function, focusing on its
      effects on the AMP-activated protein kinase (AMPK) signaling pathway. The effects
      of DDD on mitochondrial energy metabolism were also investigated in rat aortic
      endothelial cells (RAECs). Type 2 diabetes were induced in rats by streptozotocin
      (STZ) combined with high fat diet. Rats were randomly divided into non
      intervention group, metformin group, simvastatin group, and early-, middle-, late
      stage DDD groups. Normal rats were used as control. All the rats received 12
      weeks of intervention or control treatment. Western blots were used to detect the
      expression of AMP-activated protein kinase alpha1 (AMPKalpha1) and peroxisome
      proliferator-activated receptor 1alpha (PGC-1alpha). Changes in the intracellular
      AMP and ATP levels were detected with ELISA. Real-time-PCR was used to detect the
      mRNA level of caspase-3, endothelial nitric oxide synthase (eNOS), and Bcl-2.
      Compared to the diabetic non-intervention group, a significant increase in the
      expression of AMPKalpha1 and PGC-1alpha were observed in the early-stage, middle
      stage DDD groups and simvastatin group (P < 0.05). The levels of Bcl-2, eNOS, and
      ATP were significantly increased (P < 0.05), while the level of AMP and caspase-3
      were decreased (P < 0.05) in the early-stage DDD group and simvastatin group.
      Early intervention with DDD enhances mitochondrial energy metabolism by
      regulating the AMPK signaling pathway and therefore may play a role in
      strengthening the defense function of large vascular endothelial cells and
      postpone the development of macrovascular diseases in diabetes.

PMID- 29329612
TI  - Clavuridins A and B, two new trinor-guaiane sesquiterpenes isolated from the
      Xisha soft coral Clavularia viridis.
AB  - In the present study, two new trinor-guaiane sesquiterpenes, named clavuridins B
      (1), and A (2), along with three known sesquiterpenes (3-5), were isolated from
      the Xisha soft coral Clavularia viridis. Their structures and absolute
      configurations were determined on the basis of spectroscopic analysis, X-ray
      diffraction analysis with Cu Kalpha radiation and by comparison with related
      model compounds. Compounds 1 and 3-5 were evaluated for their cytotoxic activity.

PMID- 29329613
TI  - New diterpenoids isolated from Leonurus japonicus and their acetylcholinesterase
      inhibitory activity.
AB  - Three new labdane diterpenoids, leojaponicone A (1), isoleojaponicone A (2) and
      methylisoleojaponicone A (3), were isolated from the herb of Leonurus japonicus.
      The chemical structures of these secondary metabolites were elucidated on the
      basis of 1D and 2D NMR, including HMQC, and HMBC spectroscopic techniques. All
      the new compounds were tested in vitro for their acetylcholinesterase and alpha
      glucosidase inhibitory activity. Compounds 1-3 exhibited low inhibitory effects
      on alpha-glucosidase with respect to acarbose and exhibited high inhibitory
      effects on acetylcholinesterase with respect to huperzine A.

PMID- 29329614
TI  - Bioassay-guided isolation of novel and selective urease inhibitors from Diospyros
      lotus.
AB  - Two new dimeric naphthoquinones, 5',8'-dihydroxy-6,6'-dimethyl-7,3'-binaphthyl
      1,4,1',4'-tetraone (1; Di-naphthodiospyrol D) and 5',8'-dihydroxy-5,8-dimethoxy
      6,6'-dimethyl-7,3'-binaphthyl-1,4,1',4'-tetraone (2; Di-naphthodiospyrol E),
      along with known naphthoquinones diospyrin (3) and 8-hydroxy diospyrin (4) were
      isolated from the chloroform fraction of extract of Diospyros lotus roots. Their
      structures were elucidated by advanced spectroscopic analyses, including HSQC,
      HMBC, NOESY, and J-resolved NMR experiments. The fractions and compounds 1-4 were
      evaluated for urease activity and phosphodiesterase-I, carbonic anhydrase-II and
      alpha-chymotrypsin enzyme inhibitory activities. Compounds 1 and 2 and their
      corresponding fractions showed significant and selective inhibitory effects on
      urease activities. The IC50 values of 1 and 2 were 260.4 +/- 6.37 and 381.4 +/-
      4.80 umol.L-1, respectively, using thiourea (IC50 = 21 +/- 0.11 umol.L-1) as the
      standard inhibitor. This was the first report demonstrating that the
      naphthoquinones class showed urease inhibition.

PMID- 29329615
TI  - Synthesis and cytotoxicity evaluation of 3-amino-2-hydroxypropoxygenistein
      derivatives.
AB  - Soy isoflavones exhibit various biological activities, such as antioxidant, anti
      tumor, anti-inflammatory, and cardiovascular protective effects. The present
      study was designed to investigate the effects of sixteen synthesized 3-amino-2
      hydroxypropoxy genistein derivatives on cell proliferation and activation of Nrf2
      (Nuclear factor erythroid 2-related factor 2)/ARE (antioxidant response elements)
      pathway in human cancer cell lines. Most of the tested compounds exerted greater
      cytotoxic activity than genistein, as measured by MTT assay. Moreover, compound
      8c showed the highest ARE-luciferase reporter activity among the test compounds.
      It strongly promoted Nrf2 nuclear translocation and up-regulated the expression
      of total Nrf2 and downstream targets NQO-1 and HO-1 at protein level. The present
      study may provide a basis for the application of isoflavone derivatives as
      Nrf2/ARE pathway inducers for cancer therapy and cancer prevention.

PMID- 29329616
TI  - Scientific integrity includes the rigour of the methods.

PMID- 29329617
TI  - DNA detection of Trypanosoma evansi: Diagnostic validity of a new assay based on
      loop-mediated isothermal amplification (LAMP).
AB  - Trypanosoma evansi (T. evansi) is the most widely spread pathogenic trypanosome
      in the world. The control of trypanosomiasis depends on accurate diagnosis and
      effective treatment. Focusing on the presence of T. evansi in Asia, we developed
      a detection assay based on tracing phosphate ions (Pi) generated during LAMP
      targeting the variant surface glycoprotein (VSG) gene of Rode Trypanozoon
      antigenic type 1.2 (RoTat 1.2 VSG). The diagnostic potential as well as the use
      of the assay as a test-of-cure method after berenil treatment, was assessed in
      mice at different time points of infection. In addition, 67 buffalo blood
      collected from Tongling county, Anhui province, as well as 42 cattle sera from
      the Shanghai area, were used to evaluate the diagnostic validity of the test. The
      detection limit of the novel LAMP assay was determined to be as low as 1 fg of T.
      evansi DNA, while the reaction time for the test was only 30min. Hence it
      outperforms both microscopy and PCR. In the test-of-cure assessment, successful
      berenil mediated cure could be confirmed within 48h after treatment. This offers
      a tremendous advantage over conventional antibody-based diagnostic tools in which
      successful cure only can be confirmed after months. In the cattle and buffalo
      screening, the LAMP was able to detect a false-negative determined sample,
      wrongly classified in a conventional microscopy and PCR screening. Finally, no
      cross-reactivity was observed with other zoonotic parasites, such as T. evansi
      type B, T. congolense, T. brucei, Schistosoma japonicum, Plasmodium falciparum,
      Leishmania donovani, Toxoplasma gondii and Angiostrongylus cantonensis. We
      conclude that the novel LAMP assay is sensitive, specific and convenient for
      field use, particularly in areas where infection incidence has become extremely
      low. The LAMP assay could be used as a tool for trypanosomiasis control and
      elimination strategies in areas where T. evansi Type A infections are causing a
      threat to livestock farming.

PMID- 29329618
TI  - Vaccination against Fasciola hepatica using cathepsin L3 and B3 proteases
      delivered alone or in combination.
AB  - No licensed vaccine is currently available for prevention of Fasciola hepatica
      infections. However, considering the alarming increase in drug resistance, there
      is an urgent need for a safe and fully effective vaccine against fasciolosis.
      Here, we tested if cathepsins L (FhCL3-1, FhCL3-2) and B (FhCB3) secreted by
      juvenile liver flukes are viable vaccine targets when delivered alone or in
      combination in a rat model. Since control over the early immune response is
      crucial for parasite's establishment in its host, it was hypothesised that
      targeting fluke juvenile stages may prove beneficial. Moreover, it was assumed
      that selected antigens will act in a cumulative manner to interfere with liver
      fluke migration and thereby will reduce F. hepatica infection. Recombinant FhCL3
      1 and FhCL3-2 delivered alone reduced liver fluke burdens by 47 % and 63 %,
      respectively. A trivalent vaccine containing rFhCL3-1/CL3-2/CB3 did not increase
      the protective vaccine efficacy compared to the rFhCL3-2 vaccinated group (53 %),
      although, reductions in liver fluke wet weight (statistically significant) and
      liver damage score were most pronounced. Further, the highest IgG1 and IgG2a
      levels were seen in rFhCL3-2 vaccinated rats, the group for which the highest
      reduction in worm burden was demonstrated. Moreover, IgG1 and IgG2a levels in
      vaccinated rats were significantly elevated compared to those reported for
      control groups up to 4 week post-infection. While the mechanism of protection
      remains unknown, it appears that it depends on vaccine-induced antibodies
      directed against cathepsins. The obtained results imply that F. hepatica juvenile
      specific cathepsins are promising vaccine candidates that induce responses that
      successfully target early migratory liver fluke stages. Now, the challenge is to
      evaluate these juvenile-specific cathepsins for use in livestock.

PMID- 29329619
TI  - Hepatic fibropoiesis in dogs naturally infected with Leishmania (Leishmania)
      infantum treated with liposome-encapsulated meglumine antimoniate and
      allopurinol.
AB  - Hepatic fibropoiesis in canine visceral leishmaniasis (CVL) were evaluated by
      histological (morphometrical collagen deposition) and immunohistochemical assays
      characterizing alpha-actin (alpha-SMA), vimentin, calprotectin (L1 antigen), and
      TGF-beta in 46 naturally infected dogs with Leishmania infantum treated with
      liposome-encapsulated meglumine antimoniate and allopurinol separately and in
      combination. Six treatment groups were defined: meglumine antimoniate
      encapsulated in nanometric liposomes (LMA), allopurinol (ALLOP); liposome
      encapsulated meglumine antomoniate combined with allopurinol (LMA+ALLOP); empty
      liposomes (LEMP); empty liposomes combined with allopurinol (LEMP+ALLOP) and
      saline. Relative liver weight was lower in LMA, LMA+ALLOP, and ALLOP groups
      compared to the LEMP control. Significantly lower granulomatous chronic
      inflammatory reaction was seen in the ALLOP group compared to a control group.
      Calprotectin was lowest in liver of those dogs showing lower numbers of
      intralobular hepatic granulomas. Collagen deposits were significantly higher in
      LMA compared to ALLOP, LEMP+ALLOP, and Saline groups. LMA+ALLOP group collagen
      deposition was higher than dogs treated only with allopurinol.
      Immunohistochemical analysis showed significant higher alpha-SMA in hepatic
      stellate cells (HSCs), hepatic perisinusoidal cells, in control groups than
      LMA+ALLOP and LEMP+ALLOP. Alpha-actin and Vimentin positive cells were diffusely
      distributed throughout the liver parenchyma in the hepatic lobule, mainly in
      HSCs. Vimentin expression was significantly higher in the saline group than in
      the ALLOP group. Our data suggest that allopurinol inhibits HSC and results in
      lower collagen deposits in liver during CVL progression, as supported by the
      significantly lower expression of TGF-beta in the ALLOP group compared to other
      groups. Results demonstrated that treatment with allopurinol inhibited chronic
      granulomatous inflammatory reaction and hepatic fibrosis in CVL.

PMID- 29329621
TI  - First parasitological, histopathological and molecular characterization of
      Echinococcus vogeli Rausch and Bernstein, 1972 from Cuniculus paca Linnaeus, 1766
      in the Cerrado biome (Mato Grosso do Sul, Brazil).
AB  - Polycystic echinococcosis (PE) is caused by Echinococcus vogeli metacestodes
      (larval stage) in Neotropical countries. E. vogeli is trophically-transmitted
      between predators bush dogs (Speothos venaticus) and prey pacas (Cuniculus paca).
      In Brazil, reported PE cases are restricted to the Amazon biome. In this study,
      metacestodes from a paca hunted in Mato Grosso do Sul state (Cerrado biome) were
      identified morphological and histopathological techniques and further confirmed
      by molecular testing (sequencing of cytochrome C oxidase subunit I (cox1) gene)
      for the first time. Images of the whole liver showed superficial bubble-like
      hepatic masses. The parasitological analysis revealed large hooks (41.3 +/- 1.2
      MUm length/12.8 +/- 0.8 MUm width) and small hooks (33.0 +/- 1.5 MUm length/11.1
      +/- 1.2 MUm width), consistent with E. vogeli. Microscopically, the liver showed
      protoscoleces, a thick laminated layer, fibrosis, and inflammatory infiltrate in
      the adventitial layer. The DNA sequencing confirmed E. vogeli with 99% homology
      with sequences deposited in the GenBank. In addition, this finding greatly
      extends the geographic range of animal polycystic echinococcosis into the
      Cerrado. It is likely to occur in new biomes, where bush dogs and pacas share a
      given area in a trophic relationship.

PMID- 29329620
TI  - Determination and validation of discriminating concentration of ivermectin
      against Rhipicephalus microplus.
AB  - Rhipicephalus microplus, the major cattle tick species of India is prevalent all
      over the country and causes huge economic loss directly or indirectly to the
      dairy industries. Chemical acaricides are playing an important role in managing
      tick infestations on livestock for many years and consequently, resistance to
      commonly used organophosphate (OP) and synthetic pyrethroid (SP) compounds has
      been reported. Subsequently, ivermectin (IVM) has been emerged as an alternative
      to manage OP and SP resistant ticks. However, with the increase of use during the
      last 5-8 years, there is a possibility of development of resistance and thus
      there is an urgent need to develop a robust resistance monitoring tool to
      safeguard the drug. Lethal concentrations for 50 and 95% mortality of treated
      ticks were determined to work out discriminating concentration (DC) in order to
      diagnose resistance in the field situation. The DC (2 x LC95) was determined as
      93.54 ppm using an established reference susceptible IVRI-1 line of R. microplus
      adopting adult immersion test. For validation of DC, the resistance status was
      checked in seven tick isolates of R. microplus collected from northern and
      eastern regions of India. The RR50 and RR95 values of the field isolates against
      ivermectin were determined and were in the range of 1.56-8.25 and 1.93-27.58,
      respectively. All the collected isolates were found to have higher lethal
      concentration and resistance ratio in comparison to reference susceptible IVRI-1
      tick line (LC50 = 21.68, LC95 = 46.77 ppm, RR = 1.0). Amongst the field isolates,
      the isolate collected from Fatehgarh Sahib district (FTG) of Punjab state showed
      highest RR50 of 8.25 indicating high level of resistance to IVM. The generated DC
      will be used for IVM resistance characterization of ticks infesting cattle in
      different parts of the country.

PMID- 29329622
TI  - Prevalence and molecular characterization of Giardia duodenalis in cattle and
      sheep from the Qinghai-Tibetan Plateau Area (QTPA), northwestern China.
AB  - Giardia duodenalis is an important intestinal protozoan parasite with a wide
      range of hosts, including humans, livestock and wildlife. The purpose of this
      study was to determine the prevalence of G. duodenalis infections among cattle
      and sheep in the Qinghai-Tibetan Plateau Area (QTPA) and to assess the potential
      risk of the zoonotic transmission of this pathogen. A total of 454 stool
      specimens were collected and examined using the nested PCR method based on the G.
      duodenalis SSUrRNA gene fragment. Thirty-nine out of 389 cattle specimens
      examined were positive (10%) for the G. duodenalis infection. After the sequence
      analysis of the SSUrRNA gene, all detected G. duodenalis belong to assemblage E.
      No G. duodenalis infections were found in the 65 investigated samples from sheep.
      Our data therefore indicates that G. duodenalis is a common parasite in cattle in
      the QTPA, China and that cattle appear to be a reservoir of G. duodenalis for
      other animals and the environmental water supplies in the area.

PMID- 29329623
TI  - Parasite control strategies used by equine owners in the United States: A
      national survey.
AB  - The widespread occurrence of anthelmintic resistance in equine parasites across
      the world has led to recommendations of fecal egg count-based parasite programs
      to reduce treatment intensity and thereby delay further development of resistance
      as much as possible. The most recent study describing equine parasite control in
      the United States was conducted 20 years ago, and little is known about current
      strategies employed. This study was part of the National Animal Health Monitoring
      Systems (NAHMS) Equine 2015 Study, and aimed to describe equine parasite control
      strategies in the U.S. and evaluate to which extent respondents were in
      compliance with current guidelines. The study was carried out in 28 states,
      representing 70.9% of all equine operations with at least five equids present.
      Two questionnaires were administered, either by mail or delivered in person by
      veterinary medical officers. Participants provided specific details of their
      operation and were asked questions about strategies for anthelmintic therapy and
      diagnostic testing. A total of 380 operations provided data regarding their
      parasite control practices. Most respondents dewormed 2-3 times a year with
      ivermectin being the most commonly used anthelmintic. About 22% of respondents
      used fecal egg counts (FEC) in some form, with less than 10% using them on a
      regular basis. Less than 5% made use of fecal egg count reduction tests (FECRT).
      These results suggest little change since the last nationwide survey was
      conducted in 1998, as the majority of respondents did not report using FECs. This
      is in stark contrast to recent European surveys, where 50-60% of respondents were
      using FECs routinely. However, the anthelmintic treatment intensity appears to
      have been lowered compared to 1998. Taken together, these results suggest a
      continuing need for education and outreach regarding sustainable parasite
      control.

PMID- 29329624
TI  - Apparent prevalence of and risk factors for infection with Ostertagia ostertagi,
      Fasciola hepatica and Dictyocaulus viviparus in Swiss dairy herds.
AB  - Infections with helminth parasites can negatively affect performance of dairy
      cows. Knowledge on infection intensity, spatial distributions and risk factors
      are key to develop targeted treatment strategies. Canada and most EU countries
      have conducted large investigations, but respective data for Switzerland were
      missing. We now performed a bulk tank milk serosurvey for Ostertagia ostertagi,
      Fasciola hepatica, and Dictyocaulus viviparus on a total of 1036 voluntarily
      participating dairy herds that were sampled at confinement periods, i.e. in
      winter 2014/15 or 2015/16, respectively. All samples were analyzed with
      commercial ELISAs for antibodies (AB) against O. ostertagi and F. hepatica, and
      those of the first sampling period additionally with an in-house ELISA for AB
      against D. viviparus. Testing for the latter parasite was not done in the second
      year of the study, as the sampling period might have missed infections due to the
      short lived nature of specific antibodies. The possible influence of geographic,
      climatic, and farm management variables on AB levels were assessed for each
      parasite using scanning cluster and multiple regression analysis. Overall
      seroprevalence for O. ostertagi was 95.5% (95% C.I.: 94.0-96.6), with a mean
      optical density ratio (ODR) of 0.83, for F. hepatica 41.3% (95% C.I.: 38.3-44.4),
      and for D. viviparus 2.9% (95% C.I.: 1.6-4.7). There were no significant
      differences between the two sampling periods. For all parasites, significant
      geographic clusters of higher AB levels could be established. Furthermore, AB
      levels against all three parasites were positively correlated with each other,
      indicating either cross-reactions or co-infections. For O. ostertagi, herd size
      and percentage of pasture in the ration were positively correlated with AB
      levels. For F. hepatica, altitude above sea level (a.s.l.) positively, and milk
      production per cow and year was negatively correlated with AB levels. This work
      provides baseline data for further studies performing in-depth risk factor
      analysis and investigating management as well as targeted treatment options to
      control the parasites.

PMID- 29329625
TI  - Immune development and performance characteristics of Romney sheep selected for
      either resistance or resilience to gastrointestinal nematodes.
AB  - Immunological and performance characteristics were explored in Romney sheep from
      lines selected for either resistance or resilience to parasite infection. At a
      mean 78 days-of-age, twin lambs from a line selected for resistance (RT) and
      lambs from a line selected for resilience (RL) were infected with the intestinal
      nematode Trichostrongylus colubriformis for 100 days (I) while their twin
      remained as an uninfected control (C). Compared with RL, RT animals had lower
      levels of circulating CD4+ T-cells (P = 0.003) but a greater proportion of these
      were activated (CD4+CD25+) in response to infection (P = 0.007). Differences
      between the lines in humoral immune responses to nematode infection varied with
      higher levels of T. colubriformis specific immunoglobulin (Ig) E in RT-I than RL
      I (P = 0.002) but similar levels of both IgG (P = 0.926) and IgA (P = 0.321)
      responses. Temporal differences in the immune response also existed between the
      lines with RT-I animals displaying an earlier peak and more rapid reduction in
      FEC and an earlier peak in T. colubriformis specific IgA. In addition, compared
      with their RT-C and RL-C counterparts, infection caused a 22% reduction in feed
      intake from day 56 (P = 0.001) with total feed intake reduced by 15% and 9% for
      RT-I and RL-I, respectively. Cumulative liveweight gain was greatest for RL
      animals (P = 0.026) and relative to RT-C and RL-C was reduced by 5.8 kg and 4.9
      kg for RT-I and RL-I, respectively. Overall, the selection lines appear to have
      differences in immunological characteristics that are both dependent on, and
      independent of parasite infection. Further, the difference in growth in the
      uninfected animals coupled with the similar cost of infection suggests the lower
      liveweight gain of RT-I compared with RL-I may be due to inherent differences
      between the lines in their growth potential, rather than a greater cost of
      infection in animals selected for resistance.

PMID- 29329626
TI  - Applicability of FLOTAC(r) technique in recovering equine strongyle larvae in the
      pasture: A comparison study.
AB  - The FLOTAC(r) technique represents a highly sensitive method for the isolation of
      oocysts, eggs, and larvae of parasites in faeces. This assay could be used for
      detecting free-living stages of nematodes in the pasture but no attempt has been
      assessed so far. Therefore, the performance of FLOTAC(r) technique for isolating
      infective larvae of nematodes in the environment was investigated and compared
      with the spontaneous sedimentation (SST) and centrifugal sedimentation (CST)
      techniques. The study was conducted in a horse farm located in northeastern
      Brazil, where the occurrence of strongyle larvae had been previously reported.
      Pasture samplings were collected monthly from January to May 2016 in a 376 m2
      crop area harvested with the Guinea grass Panicum cultivar Massai. The recovery
      of third-stage larvae (L3) was performed using the FLOTAC(r), SST and CST
      techniques. Values of Cohen's kappa coefficient, sensitivity, specificity,
      positive and negative predictive values, and accuracy of each technique were
      assessed. Although strongyle larvae were evenly detected, with the FLOTAC(r)
      technique yielded the highest number of positive samples (i.e., 41%, 41/100, p <
      .0001). The main parasites isolated belonged to the Cyathostominae and
      Strongylinae subfamilies. Based on these results, the FLOTAC(r) technique should
      be considered as practical and safe method for the isolation of nematode larvae
      in the pasture, thus opening a new potential use for this tool in the field.

PMID- 29329627
TI  - Comparative efficacy of curcumin and paromomycin against Cryptosporidium parvum
      infection in a BALB/c model.
AB  - Cryptosporidium is a ubiquitous protozoan parasite causing gastrointestinal
      disorder in various hosts worldwide. The disease is self-limiting in the
      immunocompetent but life-threatening in immunodeficient individuals.
      Investigations to find an effective drug for the complete elimination of the
      Cryptosporidium infection are ongoing and urgently needed. The current study was
      undertaken to examine the anti-cryptosporidial efficacy of curcumin in
      experimentally infected mice compared with that of paromomycin. Oocysts were
      isolated from a pre-weaned dairy calf and identified as Cryptosporidium parvum
      using a nested- polymerase chain reaction (PCR) on Small subunit ribosomal
      ribonucleic acid (SSU rRNA) gene and sequencing analysis. One hundred and ten
      female BALB/c mice were divided into five groups. Group 1 was infected and
      treated with curcumin; Group 2 infected and treated with paromomycin; Group 3
      infected without treatment; Group 4 included uninfected mice treated with
      curcumin, and Group 5 included uninfected mice treated with distilled water for
      11 successive days, starting on the first day of oocyst shedding. The oocyst
      shedding was recorded daily. At days 0, 3, 7, and 11 of post treatments, five
      mice from each group were killed humanly; jejunum and ileum tissue samples were
      processed for histopathological evaluation and counting of oocyst on villi,
      simultaneously. Furthermore, total antioxidant capacity (TAC) and malondialdehyde
      (MDA) concentrations in affected tissues were also measured in different groups.
      By treatments, tissue lesions and the number of oocyst on villi of both jejunum
      and ileum were decreased with a time-dependent manner. In comparison with Group
      3, oocyst shedding was stopped at the end of treatment period in both groups 1
      and 2 without recurrence at 10days after drug withdrawal. Also, TAC was increased
      and the MDA concentrations were decreased in Group 1. Moreover, paromomycin
      showed acceptable treatment outcomes during experiment and its anti
      cryptosporidial activity was faster than curcumin. The results confirmed the anti
      cryptosporidial and antioxidant activity of curcumin against C. parvum and
      further evaluation of immunosuppressed animal models needs to be carried out.

PMID- 29329628
TI  - Spirocerca lupi induced oesophageal neoplasia: Predictors of surgical outcome.
AB  - Canine spirocercosis is caused by the nematode Spirocerca lupi. Migration results
      in oesophageal fibro-inflammatory nodules that may undergo neoplastic
      transformation. No studies have assessed pre- or post-surgical prognostic
      indicators in dogs that undergo intervention for S. lupi induced oesophageal
      neoplasia. This observational, multi-center study aimed to assess the outcome of
      dogs with Spirocerca induced sarcoma undergoing endoscopic-guided ablation (n =
      12) or surgery (n = 18), and identify prognostic indicators. Parameters evaluated
      included: age, weight, gender, presenting complaints, duration of clinical signs,
      complete blood count, serum biochemistry, neoplasia size, placement of
      percutaneous endoscopically-placed gastrostomy tube, histopathological mitotic
      indices, days to discharge and chemotherapy administration. Kaplan-Meier survival
      curves showed no difference in survival between ablation and surgery {(median:
      73.5 days (range: 0-1511) vs. 108 days (range: 0-1550), respectively (p =
      0.982)}. Reduced survival was documented in patients presenting with weight loss
      (P = 0.027), hypochromasia (MCHC <33 g/dL, P = 0.023) or leucocytosis (>15 *
      109/L, P = 0.017) with a hazard ratio of 2.51 (CI95% = 1.071-6.018, P = 0.034),
      2.71 (CI95% = 1.10-6.65, P = 0.03) and 4.39 (CI95%: 1.21-15.97, P = 0.025)
      respectively. In the dogs surviving more than 21 days, Ht <36% and leucocytosis
      >15.0 * 109/L at presentation were associated with reduced survival (p = 0.016, p
      = 0.021 respectively) and hazard ratio of 3.29 (CI95% = 1.18-9.2, P = 0.023) and
      3.81 (CI95% = 1.15-12.55, P = 0.028) respectively. Intra-intervention-group
      survival analysis identified increased survival time in dogs receiving
      chemotherapy, but only within the surgical group (P = 0.02).The hospitalisation
      time of dogs undergoing ablation (median: 0 days, range: 0-4) was significantly
      shorter than dogs undergoing surgery (9 days, 1-21) (P < 0.001). In this study,
      no clear benefit was identified for surgery, thus when ablation is technically
      possible it should be considered advantageous, as hospitalisation time is
      significantly shorter. Weight loss, hypochromasia and leucocytosis were
      identified as long-term prognostic indicators at presentation.

PMID- 29329629
TI  - Estimates of repeatability and correlations of hemoparasites infection levels for
      cattle reared in endemic areas for Rhipicephalus microplus.
AB  - Rhipicephalus microplus is a vector of cattle tick fever, a disease caused by the
      protozoans Babesia bovisand B. bigemina, and also anaplasmosis, produced by the
      Rickettsiales Anaplasma marginale. These tick-borne pathogens cause considerable
      losses to Brazilian livestock breeders and represent an obstacle to the expanded
      use of taurine breeds due to their higher sensitivity to ticks and hemoparasites
      compared to zebu breeds. Differences in the susceptibility to hemoparasites were
      also verified within breeds, suggesting that may be possible to select a most
      resistant phenotype. Therefore, repeatability of R. microplus counts and copy
      number of hemoparasites DNA were estimated, along with correlations between
      themselves, aiming to verify if those measures can be used as parameters to
      classify animals according to their parasite resistance degrees. Forty-two
      Canchim females kept on pastures naturally infested by ticks were evaluated for
      the level of infestation by R. microplus and infection by B. bovis, B. bigemina,
      and A. marginale. Twenty-four evaluations were performed once a month, for adult
      female ticks counts and blood samplings. The experimental period was divided into
      four phases, according to the animals age range: Phase 1: 8 to 13 months
      (collections 1 to 6); phase 2: 14 to 19 months (collections 7 to 12); phase 3: 20
      to 25 months (collections 13 to 18), and phase 4: 26 to 31 months (collections 19
      to 24). Blood samples were submitted to absolute quantification of hemoparasites
      DNA sequences using qPCR. The hemoparasite and tick counts data were transformed
      for normalization and were analyzed using mixed models. Among three species of
      hemoparasites studied, A. marginale presented the highest level of infection.
      During phase 3, B. bigemina presented higher infection levels (p < 0.05) compared
      to B. bovis, whereas no differences were observed in other phases. Estimated
      repeatabilities for parasite infection levels varied from low to moderate during
      our experiment. There were low correlations between tick counts and parasite
      infection levels, and between parasite infection levels from different species by
      themselves. Based on these results, under conditions of the present study, we
      suggest that it is possible to identify animals presenting a most resistant
      phenotype against infection by both hemoparasites and ticks. Moreover, the animal
      age may be an important factor related to resistance against these pathogens. The
      data obtained shed more light on the resistance to hemoparasites studied.

PMID- 29329630
TI  - Reply.

PMID- 29329631
TI  - Comments on: Walsh and Tobias, "Low-Pressure Pericardial Tamponade: Case Report
      and Review of the Literature".

PMID- 29329633
TI  - Pediatric Adnexal Torsion: Not Just a Postmenarchal Problem.

PMID- 29329634
TI  - Pediatric Adnexal Torsion.

PMID- 29329635
TI  - Converting the Easy Internal Jugular (IJ) to a Central Line.

PMID- 29329636
TI  - The Unique Environmental Influences of Acute Care Settings on Patient and
      Physician Well-Being: A Call to Action.

PMID- 29329638
TI  - Role of the IL-33/ST2L axis in colorectal cancer progression.
AB  - Interleukin-33 (IL-33) has been identified as a natural ligand of ST2L. IL-33
      primarily acts as a key regulator of Th2 responses through binding to ST2L, which
      is antagonized by soluble ST2 (sST2). The IL-33/ST2L axis is involved in various
      inflammatory pathologies, including ulcerative colitis (UC). Several recent
      investigations have also suggested that the IL-33/ST2L axis plays a role in
      colorectal cancer (CRC) progression. In CRC, tumor- and stroma-derived IL-33 may
      activate ST2L on various cell types in an autocrine and paracrine manner.
      Although several findings support the hypothesis that the IL-33/ST2L axis
      positively regulates CRC progression, other reports do not; hence, this
      hypothesis remains controversial. At any rate, recent studies have provided
      overwhelming evidence that the IL-33/ST2L axis plays important roles in CRC
      progression. This review summarizes the role of the IL-33/ST2L axis in the UC and
      CRC microenvironments.

PMID- 29329639
TI  - Vestibular stimulation makes people more egocentric.

PMID- 29329637
TI  - Transcriptomic evidence of immune activation in macroscopically normal-appearing
      and scarred lung tissues in idiopathic pulmonary fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease manifested by overtly
      scarred peripheral and basilar regions and more normal-appearing central lung
      areas. Lung tissues from macroscopically normal-appearing (IPFn) and scarred
      (IPFs) areas of explanted IPF lungs were analyzed by RNASeq and compared with
      healthy control (HC) lung tissues. There were profound transcriptomic changes in
      IPFn compared with HC tissues, which included elevated expression of numerous
      immune-, inflammation-, and extracellular matrix-related mRNAs, and these changes
      were similar to those observed with IPFs compared to HC. Comparing IPFn directly
      to IPFs, elevated expression of epithelial mucociliary mRNAs was observed in the
      IPFs tissues. Thus, despite the known geographic tissue heterogeneity in IPF, the
      entire lung is actively involved in the disease process, and demonstrates
      pronounced elevated expression of numerous immune-related genes. Differences
      between normal-appearing and scarred tissues may thus be driven by deranged
      epithelial homeostasis or possibly non-transcriptomic factors.

PMID- 29329640
TI  - Capturing real-life forgetting in transient epileptic amnesia via an incidental
      memory test.
AB  - Transient epileptic amnesia (TEA) is an epileptic syndrome characterized by
      recurrent, brief episodes of amnesia. Patients with TEA often complain of
      interictal (between attacks) retention deficits, characterised by an
      'evaporation' of memories for recent events over days to weeks. Clinical tests of
      anterograde memory often fail to corroborate these complaints as TEA patients
      commonly perform within the normal range after the standard 10-30-min delay
      period. Modified laboratory tests that include a 1-3 week delay period frequently
      reveal clear evidence of 'accelerated long-term forgetting' (ALF). However, they
      are not used routinely and lack ecological validity. In the present study we
      examined whether 'real-life' ALF can be captured via a controlled incidental
      memory test in TEA patients. To this end, the experimenter told 27 TEA patients
      and 32 controls a well-rehearsed amusing story, apparently as a way of making
      light conversation before starting a set of research experiments. Without prior
      warning, the experimenter subsequently probed the participants' memory of this
      story via tests of free recall and forced choice recognition after 30 min or 1
      week. After 30 min retention was comparable in TEA patients and controls. After 1
      week TEA patients retained significantly less story material than controls, and
      significant ALF was revealed in the TEA patients in the recognition test. Our
      data show that ALF in a 'real-life' situation can occur even when standard memory
      tests indicate normal memory function. Moreover, our data suggest that incidental
      memory tests can capture real-life ALF, and that forced-choice recognition tests
      might be more sensitive than free recall tests for the detection of real-life
      ALF.

PMID- 29329641
TI  - Discussion of "Nonatherosclerotic vascular causes of acute abdominal pain".

PMID- 29329643
TI  - IgA nephropathy and IgA vasculitis with nephritis have a shared feature involving
      galactose-deficient IgA1-oriented pathogenesis.
AB  - Galactose-deficient IgA1 has been proposed as an important effector molecule in
      IgA nephropathy (IgAN). We previously showed that the galactose-deficient IgA1
      specific monoclonal antibody KM55 can detect circulating galactose-deficient IgA1
      in patients with IgAN, enabling us to study the molecular roles of galactose
      deficient IgA1. Herein, we further examined the pathophysiological significance
      of galactose-deficient IgA1 in glomerular deposits of patients with IgAN by
      immunohistochemistry using KM55. Immunostaining of galactose-deficient IgA1 with
      KM55 was performed in paraffin-embedded sections of renal biopsy specimens from
      48 patients with IgAN and 49 patients with other renal diseases such as lupus
      nephritis, HCV-related nephropathy, IgA vasculitis with nephritis (IgA-VN), and
      membranous nephropathy. Glomerular galactose-deficient IgA1 was specifically
      detected in IgAN and IgA-VN but not in the other renal diseases. Galactose
      deficient IgA1 was localized predominantly in the mesangial region as IgA
      deposition. However, galactose-deficient IgA1 was not detected in patients with
      lupus nephritis accompanied by glomerular IgA deposition. Thus, our study
      strongly suggests that IgAN and IgA-VN have a shared feature regarding galactose
      deficient IgA1-oriented pathogenesis.

PMID- 29329644
TI  - Anticancer carbazole alkaloids and coumarins from Clausena plants: A review.
AB  - Pharmaceutical research has focused on the discovery and development of
      anticancer drugs. Clinical application of chemotherapy drugs is limited due to
      their severe side effects. In this regard, new naturally occurring anticancer
      drugs have gained increasing attention because of their potential effectiveness
      and safety. Fruits and vegetables are promising sources of anticancer remedy.
      Clausena (family Rutaceae) is a genus of flowering plants and includes several
      kinds of edible fruits and vegetables. Phytochemical and pharmacological studies
      show that carbazole alkaloids and coumarins from Clausena plants exhibit
      anticancer activity. This review summarizes research progresses made in the
      anticancer properties of plants belonging to Clausena; in particular, compounds
      with direct cytotoxicity, cell cycle arrest, apoptosis induction, and immune
      potentiation effects are discussed. This review reveals the potential use of
      plants from Clausena in preventing and treating cancer and provides a basis for
      development of relevant therapeutic agents.

PMID- 29329642
TI  - Mesenchymal stem cell-macrophage crosstalk and bone healing.
AB  - Recent research has brought about a clear understanding that successful fracture
      healing is based on carefully coordinated cross-talk between inflammatory and
      bone forming cells. In particular, the key role that macrophages play in the
      recruitment and regulation of the differentiation of mesenchymal stem cells
      (MSCs) during bone regeneration has been brought to focus. Indeed, animal studies
      have comprehensively demonstrated that fractures do not heal without the direct
      involvement of macrophages. Yet the exact mechanisms by which macrophages
      contribute to bone regeneration remain to be elucidated. Macrophage-derived
      paracrine signaling molecules such as Oncostatin M, Prostaglandin E2 (PGE2), and
      Bone Morphogenetic Protein-2 (BMP2) have been shown to play critical roles;
      however the relative importance of inflammatory (M1) and tissue regenerative (M2)
      macrophages in guiding MSC differentiation along the osteogenic pathway remains
      poorly understood. In this review, we summarize the current understanding of the
      interaction of macrophages and MSCs during bone regeneration, with the emphasis
      on the role of macrophages in regulating bone formation. The potential
      implications of aging to this cellular cross-talk are reviewed. Emerging
      treatment options to improve facture healing by utilizing or targeting MSC
      macrophage crosstalk are also discussed.

PMID- 29329645
TI  - Polysaccharides extracted from the roots of Bupleurum chinense DC modulates
      macrophage functions.
AB  - The present study aimed to investigate the effects of polysaccharides extracted
      from Bupleurum chinense DC (BCPs) on macrophage functions. In the in vivo
      experiment, 1 mL of 5% sodium thioglycollate was injected into the abdomen of the
      mice on Day 0 and macrophages were harvested on Day 4. The macrophages were
      cultured in plates and treated with different concentrations of BCPs and
      stimulus. Effects of BCPs on macrophage functions were assessed by chemotaxis
      assay, phagocytosis assay and Enzyme-Linked Immunosorbent Assay (ELISA). Our
      results showed the enhanced chemotaxis, phagocytosis and secretion of nitric
      oxide (NO) and inflammatory cytokines by macrophages when treated with BCPs.
      However, when chemotaxis and phagocytosis were up-regulated by complement
      components or opsonized particles, BCPs inhibited these effects. Also, the NO
      production induced by lipopolysaccharides (LPS) was suppressed by BCPs mildly.
      Moreover, BCPs had an inhibitory effect on the [Ca2+]i elevation of macrophages.
      These results suggested that BCPs exerted modulatory effects on macrophage
      functions, which may contribute to developing novel approaches to treating
      inflammatory diseases.

PMID- 29329646
TI  - Effects of Gardenia jasminoides extracts on cognition and innate immune response
      in an adult Drosophila model of Alzheimer's disease.
AB  - Herbal extracts have been extensively used worldwide for their application on
      memory improvement, especially among aged and memory-deficit populations. In the
      present study, the memory loss induced by human Abeta protein over-expression in
      fruitfly Alzheimer's disease (AD) model was rescued by multiple extracts from
      Gardenia jasminoides. Three extracts that rich with gardenia yellow, geniposide,
      and gardenoside components showed distinct rescue effect on memory loss. Further
      investigation on adding gardenoside into a formula of Ganoderma lucidum, Panax
      notoginseng and Panax ginseng (GPP) also support its therapeutic effects on
      memory improvement. Interestingly, the application of GPP and gardenoside did not
      alter the accumulation of Abeta proteins but suppressed the expression of immune
      related genes in the brain. These results revealed the importance and relevancy
      of anti-inflammation process and the underlying mechanisms on rescuing memory
      deficits, suggesting the potential therapeutic use of the improved GPP
      formulation in improving cognition in defined population in the future.

PMID- 29329647
TI  - Atractylodes lancea rhizome water extract reduces triptolide-induced toxicity and
      enhances anti-inflammatory effects.
AB  - The present study was designed to explore the influence of water extracts of
      Atractylodes lancea rhizomes on the toxicity and anti-inflammatory effects of
      triptolide (TP). A water extract was prepared from A. lancea rhizomes and co
      administered with TP in C57BL/6 mice. The toxicity was assayed by determining
      serum biochemical parameters and visceral indexes and by liver histopathological
      analysis. The hepatic CYP3A expression levels were detected using Western
      blotting and RT-PCR methods. The data showed that the water extract of A. lancea
      rhizomes reduced triptolide-induced toxicity, probably by inducing the hepatic
      expression of CYP3A. The anti-inflammatory effects of TP were evaluated in mice
      using a xylene-induced ear edema test. By comparing ear edema inhibition rates,
      we found that the water extract could also increase the anti-inflammatory effects
      of TP. In conclusion, our results suggested that the water extract of A. lancea
      rhizomes, used in combination with TP, has a potential in reducing TP-induced
      toxicity and enhancing its anti-inflammatory effects.

PMID- 29329648
TI  - Preparation and physicochemical characterization of T-OA PLGA microspheres.
AB  - As the carrier of water-insoluble drugs, microspheres can play a role in
      increasing solubility and delaying releasing essence. The objective of this study
      was to improve the solubility and to delay the release of a newly discovered
      antitumor compound 3beta-hydroxyolea-12-en-28-oic acid-3, 5, 6-trimethylpyrazin-2
      methyl ester (T-OA). Early-stage preparation discovery concept (EPDC) was
      employed in the present study. The preparation, physicochemical characterization,
      and drug release properties of PLGA microspheres were evaluated. T-OA-loaded PLGA
      microspheres were prepared by an oil-in-water (O/W) emulsification solvent
      evaporation method. Characterization and release behaviors of the T-OA PLGA
      microspheres were evaluated by X-ray diffract (XRD), differential scanning
      calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), scanning
      electron microscopy (SEM), and high performance liquid chromatography (HPLC). The
      results demonstrated that T-OA-loaded PLGA microspheres could be successfully
      obtained through solvent evaporation method with appropriate morphologic
      characteristics and high encapsulation efficiency. The XRD analysis showed that T
      OA would be either molecularly dispersed in the polymer or distributed in an
      amorphous form. The DSC and FTIR analysis proved that there were interactions
      between T-OA and PLGA polymer. SEM observations displayed the morphology of the
      microspheres was homogeneous and the majority of the spheres ranged between 50
      and 150 MUm. The drug release behavior of the microspheres in the phosphate
      buffered saline medium exhibited a sustained release and the duration of the
      release lasted for more than 23 days, which was fit with zero-order release
      pattern with r2 = 0.9947. In conclusion, TOA-loaded PLGA microspheres might hold
      great promise for using as a drug-delivery system in biomedical applications.

PMID- 29329649
TI  - HPPR encodes the hydroxyphenylpyruvate reductase required for the biosynthesis of
      hydrophilic phenolic acids in Salvia miltiorrhiza.
AB  - Salvia miltiorrhiza is a medicinal plant widely used in the treatment of
      cardiovascular and cerebrovascular diseases. Hydrophilic phenolic acids,
      including rosmarinic acid (RA) and lithospermic acid B (LAB), are its primary
      medicinal ingredients. However, the biosynthetic pathway of RA and LAB in S.
      miltiorrhiza is still poorly understood. In the present study, we accomplished
      the isolation and characterization of a novel S. miltiorrhiza
      Hydroxyphenylpyruvate reductase (HPPR) gene, SmHPPR, which plays an important
      role in the biosynthesis of RA. SmHPPR contained a putative catalytic domain and
      a NAD(P)H-binding motif. The recombinant SmHPPR enzyme exhibited high HPPR
      activity, converting 4-hydroxyphenylpyruvic acid (pHPP) to 4-hydroxyphenyllactic
      acid (pHPL), and exhibited the highest affinity for substrate 4
      hydroxyphenylpyruvate. SmHPPR expression could be induced by various treatments,
      including SA, GA3, MeJA and Ag+, and the changes in SmHPPR activity were
      correlated well with hydrophilic phenolic acid accumulation. SmHPPR was localized
      in cytoplasm, most likely close to the cytosolic NADPH-dependent hydroxypyruvate
      reductase active in photorespiration. In addition, the transgenic S. miltiorrhiza
      hairy roots overexpressing SmHPPR exhibited up to 10-fold increases in the
      products of hydrophilic phenolic acid pathway. In conclusion, our findings
      provide a new insight into the synthesis of active pharmaceutical compounds at
      molecular level.

PMID- 29329650
TI  - Synthesis and anti-hepatocellular carcinoma activity of novel O2-vinyl
      diazeniumdiolate-based nitric oxide-releasing derivatives of oleanolic acid.
AB  - Considering that high levels of nitric oxide (NO) exert anti-cancer effect and
      the derivatives of oleanolic acid (OA) have shown potent anti-cancer activity,
      new O2-vinyl diazeniumdiolate-based NO releasing derivatives (5a-l, 11a-l) of OA
      were designed, synthesized, and biologically evaluated in the present study.
      These derivatives could release different amounts of NO in liver cells. Among
      them, 5d, 5i, 5j, 11g, 11h, and 11j released more NO in SMMC-7721 cells and
      displayed stronger proliferative inhibition against SMMC-7721 and HepG2 cells
      than OA and other tested compounds. The most active compound 5j showed almost 20
      fold better solubility than OA in aqueous solution, released larger amounts of NO
      in liver cancer cells than that in normal ones, and exhibited potent anti
      hepatocellular carcinoma activity but little effect on the normal liver cells.
      The inhibitory activity against the cancer cells was significantly diminished
      upon addition of an NO scavenger, suggesting that NO may contribute, at least in
      part, to the activity of 5j.

PMID- 29329651
TI  - Lignans and diterpenes isolated from Tirpitzia ovoidea and their biological
      activities.
AB  - A new lignan, tirpitzin A (17) together with 20 known compounds (1-16, and 18-21)
      were isolated from the ethyl acetate soluble fraction of ethanol extract of the
      aerial parts of Tirpitzia ovoidea. The structure of new compound was elucidated
      by means of spectroscopic analysis. Of the known compounds, 7-21 were isolated
      from Linaceae family for the first time. The pharmacological activity of the
      crude extracts was tested using a mouse inflammation model induced by dimethyl
      benzene. The results demonstrated that the ethyl acetate soluble fraction had
      anti-inflammatory activity. Moreover, the cytotoxic and anti-inflammatory
      activities of some compounds were studied. The new compound 17 showed moderate
      cytotoxic effect against BxPC-3 cell line (IC50 = 19.51MUmol.L-1) and Compound 10
      showed significant cytotoxicity against HepG2, HL-60, U87 and BxPC-3 cell lines
      with IC50 values in the range 4.2-8.3MUmol.L-1. Additionally, Compounds 2, 10,
      11, and 13 exhibited potent inhibitory effects on LPS-induced nitric oxide
      production in RAW 264.7 macrophages at the concentration of 50MUmol.L-1.

PMID- 29329652
TI  - Three new anthraquinone derivatives isolated from Symplocos racemosa and their
      antibiofilm activity.
AB  - Three new alkyl substituted anthraquinone derivatives, trivially named as
      symploquinones A-C (Compounds 1-3) were isolated from Symplocos racemosa. The
      structures of these compounds were determined on the basis of extensive
      spectroscopic analyses (UV, IR, Mass, 1H- and 13C-NMR, and two-dimensional (2D)
      NMR techniques). The resulting data were also compared with the reported
      literature. These compounds were then subjected to antibacterial or antibiofilm
      testing. Compounds 1 and 3 exhibited good antibacterial activity in the
      concentration range of 160-83 MUg.mL-1 against Streptococcus mutans, methicillin
      resistant Staphylococcus aureus and Proteus mirabilis. Both compounds were
      further screened for anti-biofilm activity, which revealed promising activities
      at sub-MIC concentrations. None of the compounds were found to be active against
      Klebsiella pneumoniae.

PMID- 29329653
TI  - Cycloartane triterpenoid and its glucoside isolated from Cassia occidentalis.
AB  - In the present study, one new cycloartane triterpenoid, named cycloccidentalic
      acid C (1) and its glucoside, cycloccidentaliside VI (2) were isolated from the
      whole plant of Cassia occidentalis. Their structures were elucidated by a
      combinational analyses of 1D and 2D NMR data and HRMS. Compound 2 showed modest
      anti-HIV-1 activity with EC50 value of 1.44 MUmol.L-1 and TI (Therapeutic Index)
      value of 15.59.

PMID- 29329654
TI  - UHPLC-LTQ-Orbitrap-based metabolomics coupled with metabolomics pathway analysis
      method for exploring the protection mechanism of Kudiezi injection in a rat anti
      ischemic cerebral reperfusion damage model.
AB  - Kudiezi injection has been used extensively in the treatment of cerebrovascular
      and cardiovascular diseases. However, its therapeutic effects and underlying
      mechanism of action are not fully understood. The aim of the present study was to
      clarify the protective mechanisms of Kudiezi injection on cerebral ischemic
      injury, using metabolomics methods. Middle cerebral artery occlusion (MCAO) was
      introduced in rats to build the cerebral ischemic damage. UHPLC-LTQ-Orbitrap
      based analytical method was established for analysis of the metabolites. The raw
      mass data of all samples were normalized with Sieve 2.2 software and then
      introduced to orthogonal partial least squares discriminant analysis (OPLS-DA)
      model. Finally, 23 metabolites in plasma (15 were tentatively identified) were
      chosen as potential biomarkers, according to accurate mass measurements (< 5
      ppm), MS/MS fragmentation patterns, and diagnostic product ions. Furthermore, on
      the basis of metabolic pathway analysis via metabolomics pathway analysis
      (MetPA), we first discovered that the protection mechanism in anti-ischemic
      cerebral reperfusion damage of Kudiezi injection was possibly related to the
      biosynthesis of phenylalanine, tyrosine, and tryptophan. The present study
      provided a useful approach for exploring the mechanism of ischemic stroke and
      evaluating the efficacy of Kudiezi injection or other traditional medicines.

PMID- 29329655
TI  - [Erratum to "Cervical lift: An update" [Annales de chirurgie plastique esthetique
      2017;62:461-73. DOI: 10.1016/j.anplas.2017.08.002]].

PMID- 29329656
TI  - Techno-economic performance indicators of municipal solid waste collection
      strategies.
AB  - Several indicators for the evaluation of the MSW collection systems have been
      proposed in the literature. These evaluation tools consider only some of the
      aspects that influence the operational efficiency of the collection service. The
      aim of this paper is to suggest a set of (easy to calculate) indicators that
      overcomes this limitation, taking into account both the characteristics of
      collected waste and the operational - economic performance. The main components
      of the collection system (labour, vehicles and containers) are separately
      considered so that it is possible to quantify and compare their role within the
      whole process. As an example of application, the proposed approach was used for
      comparing the MSW collection strategies adopted in four towns in Northern Italy.
      Results are discussed and a comparison with alternative assessment methods
      available in the scientific literature is reported.

PMID- 29329657
TI  - The development and trial of an unmanned aerial system for the measurement of
      methane flux from landfill and greenhouse gas emission hotspots.
AB  - This paper describes the development of a new sampling and measurement method to
      infer methane flux using proxy measurements of CO2 concentration and wind data
      recorded by Unmanned Aerial Systems (UAS). The flux method described and trialed
      here is appropriate to the spatial scale of landfill sites and analogous
      greenhouse gas emission hotspots, making it an important new method for low-cost
      and rapid case study quantification of fluxes from currently uncertain (but
      highly important) greenhouse gas sources. We present a case study using these UAS
      based measurements to derive instantaneous methane fluxes from a test landfill
      site in the north of England using a mass balance model tailored for UAS sampling
      and co-emitted CO2 concentration as a methane-emission proxy. Methane flux (and
      flux uncertainty) during two trials on 27 November 2014 and 5 March 2015, were
      found to be 0.140 kg s-1 (+/-61% at 1sigma), and 0.050 kg s-1 (+/-54% at 1sigma),
      respectively. Uncertainty contributing to the flux was dominated by ambient
      variability in the background (inflow) concentration (>40%) and wind speed
      (>10%); with instrumental error contributing only ~1-2%. The approach described
      represents an important advance concerning the challenging problem of greenhouse
      gas hotspot flux calculation, and offers transferability to a wide range of
      analogous environments. This new measurement solution could add to a toolkit of
      approaches to better validate source-specific greenhouse emissions inventories -
      an important new requirement of the UNFCCC COP21 (Paris) climate change
      agreement.

PMID- 29329659
TI  - Discovery of Mcl-1 inhibitors based on a thiazolidine-2,4-dione scaffold.
AB  - Inspired by a rhodanine-based dual inhibitor of Bcl-xL and Mcl-1, a focused
      library of analogues was prepared wherein the rhodanine core was replaced with a
      less promiscuous thiazolidine-2,4-dione scaffold. Compounds were initially
      evaluated for their abilities to inhibit Mcl-1. The most potent compound 12b
      inhibited Mcl-1 with a Ki of 155 nM. Further investigation revealed comparable
      inhibition of Bcl-xL (Ki = 90 nM), indicating that the dual inhibitory profile of
      the initial rhodanine lead had been retained upon switching the heterocycle core.

PMID- 29329658
TI  - Novel compounds with potent CDK9 inhibitory activity for the treatment of
      myeloma.
AB  - Cyclin-dependent kinases (CDKs) and Polo-like kinases (PLKs) play key role in the
      regulation of the cell cycle. The aim of our study was originally the further
      development of our recently discovered polo-like kinase 1 (PLK1) inhibitors. A
      series of new 2,4-disubstituted pyrimidine derivatives were synthesized around
      the original hit, but their PLK1 inhibitory activity was very poor. However the
      novel compounds showed nanomolar CDK9 inhibitory activity and very good
      antiproliferative effect on multiple myeloma cell lines (RPMI-8226).

PMID- 29329660
TI  - Cochlea CT radiomics predicts chemoradiotherapy induced sensorineural hearing
      loss in head and neck cancer patients: A machine learning and multi-variable
      modelling study.
AB  - OBJECTIVES: Immediately or after head-and-neck (H&N) cancer chemoradiotherapy
      (CRT), patients may undergone significant sensorineural hearing loss (SNHL) which
      could affect their quality of life. Radiomic feature analysis is proposed to
      predict SNHL induced by CRT. MATERIAL AND METHODS: 490 image features of 94
      cochlea from 47 patients treated with three dimensional conformal RT (3DCRT) for
      different H&N cancers were extracted from CT images. Different machine learning
      (ML) algorithms and also least absolute shrinkage and selection operator (LASSO)
      penalized logistic regression were implemented on radiomic features for feature
      selection, classification and prediction. Also, LASSO penalized logistic model
      was used for outcome modelling. RESULTS: The predictive power of ten ML methods
      was more than 70% (in accuracy, precision and area under the curve of receiver
      operating characteristic curve (AUC)). According to the LASSO penalized logistic
      modelling, 10 of the 490 radiomic features selected as the associated features
      with SNHL status. All of the 10 features were statistically associated with SNHL
      (all of adjusted P-values < .001). CONCLUSION: CT radiomic analysis proposed in
      this study, could help in the prediction of hearing loss induced by
      chemoradiation. Our study also, demonstrates that combination of radiomic
      features with clinical and dosimetric variables can model radiotherapy outcome
      such as SNHL.

PMID- 29329661
TI  - The Meshed Autologous Vein.

PMID- 29329662
TI  - A Summation Analysis of Compliance and Complications of Compression Hosiery for
      Patients with Chronic Venous Disease or Post-thrombotic Syndrome.
AB  - OBJECTIVES: Compression stockings are commonly prescribed for patients with a
      range of venous disorders, but are difficult to don and uncomfortable to wear.
      This study aimed to investigate compliance and complications of compression
      stockings in patients with chronic venous disease (CVD) and post-thrombotic
      syndrome (PTS). METHODS: A literature search of the following databases was
      carried out: MEDLINE (via PubMed), EMBASE (via OvidSP, 1974 to present), and
      CINAHL (via EBSCOhost). Studies evaluating the use of compression stockings in
      patients with CVD (CEAP C2-C5) or for the prevention or treatment of PTS were
      included. After scrutinising full text articles, compliance with compression and
      associated complications were assessed. Compliance rates were compared based on
      study type and degree of compression. Good compliance was defined as patients
      wearing compression stockings for >50% of the time. RESULTS: From an initial
      search result of 4303 articles, 58 clinical studies (37 randomised trials and 21
      prospective studies) were selected. A total of 10,245 limbs were included, with
      compression ranging from 15 to 40 mmHg (not stated in 12 studies) and a median
      follow-up of 12 months (range 1-60 months). In 19 cohorts, compliance was not
      assessed and in a further nine, compliance was poorly specified. Overall, good
      compliance with compression was reported for 5371 out of 8104 (66.2%) patients.
      The mean compliance, weighted by study size, appeared to be greater for
      compression <=25 mmHg (77%) versus > 25 mmHg (65%) and greater in the randomised
      studies (74%) than in prospective observational studies (64%). Complications of
      stockings were not mentioned in 43 out of 62 cohorts reviewed. Where
      complications were considered, skin irritation was a common event. CONCLUSIONS:
      In published trials, good compliance with compression is reported in around two
      thirds of patients, with inferior compliance in those given higher degrees of
      compression. Further studies are required to identify predictors of non
      compliance, to help inform the clinical management of these patients.
      Complications of compression are not documented in many studies and should be
      given more consideration in the future.

PMID- 29329663
TI  - Reintroducing Pazopanib Reverses the Primary Resistance of Nivolumab in a Patient
      With Metastatic Clear-cell Renal Cell Carcinoma.

PMID- 29329664
TI  - The impact of mental health disorders on 30-day readmission after bariatric
      surgery.
AB  - BACKGROUND: Mental health disorders are common among bariatric surgery patients.
      Mental health disorders, particularly depression, have been associated with
      poorer surgical outcomes, indicating the bariatric surgery patient population
      warrants special clinical attention. OBJECTIVE: Our study sought to examine the
      effect of diagnosed mental health disorders on 30-day readmission for those
      undergoing bariatric surgery in hospitals across Pennsylvania from 2011 to 2014.
      METHODS: We used Pennsylvania Healthcare Cost Containment Council data to perform
      this analysis. Inclusion criteria encompassed patients aged>18 years who
      underwent bariatric surgery at any hospital or freestanding surgical facility in
      Pennsylvania between 2011 and 2014. Mental health disorders were identified using
      predetermined International Classification of Disease, Ninth Revision codes.
      Logistic regression was used to model the risk of 30-day readmission and estimate
      the effect of mental health disorders on 30-day readmission. RESULTS: Of the
      19,259 patients who underwent bariatric surgery, 40.3% had a diagnosed mental
      health disorder; 6.51% of all patients were readmitted within 30 days. Patients
      with a diagnosed mental health disorder had 34% greater odds of readmission (odds
      ratio = 1.34, 95% confidence interval: 1.19-1.51) relative to patients with no
      diagnosed mental health disorder. Patients with major depressive disorder/bipolar
      disorder had 46% greater odds of being readmitted compared with patients with no
      major depressive disorder/bipolar disorder diagnosis. CONCLUSION: Study findings
      imply the need for risk assessment of patients before postoperative discharge.
      Given that patients with mental health diagnoses are at increased risk of 30-day
      readmission after bariatric surgery, they may benefit from additional discharge
      interventions designed to attenuate potential readmissions.

PMID- 29329666
TI  - Advances in self-healing materials based on vascular networks with mechanical
      self-repair characteristics.
AB  - Here, we review the state-of-the-art in the field of engineered self-healing
      materials. These materials mimic the functionalities of various natural materials
      found in the human body (e.g., the healing of skin and bones by the vascular
      system). The fabrication methods used to produce these "vascular-system-like"
      engineered self-healing materials, such as electrospinning (including co
      electrospinning and emulsion spinning) and solution blowing (including coaxial
      solution blowing and emulsion blowing) are discussed in detail. Further, a few
      other approaches involving the use of hollow fibers are also described. In
      addition, various currently used healing materials/agents, such as
      dicyclopentadiene and Grubbs' catalyst, poly(dimethyl siloxane), and bisphenol-A
      based epoxy, are described. We also review the characterization methods employed
      to verify the physical and chemical aspects of self-healing, that is, the methods
      used to confirm that the healing agent has been released and that it has resulted
      in healing, as well as the morphological changes induced in the damaged material
      by the healing agent. These characterization methods include different
      visualization and spectroscopy techniques and thermal analysis methods. Special
      attention is paid to the characterization of the mechanical consequences of self
      healing. The effects of self-healing on the mechanical properties such as
      stiffness and adhesion of the damaged material are evaluated using the tensile
      test, double cantilever beam test, plane strip test, bending test, and adhesion
      test (e.g., blister test). Finally, the future direction of the development of
      these systems is discussed.

PMID- 29329665
TI  - Bioactivation of 1-chloro-2-hydroxy-3-butene, an in vitro metabolite of 1,3
      butadiene, by rat liver microsomes.
AB  - 1-Chloro-2-hydroxy-3-butene (CHB) is an in vitro metabolite of 1,3-butadiene, a
      rodent/human carcinogen. To search for an approach detecting CHB in vivo, it is
      vital to obtain a full understanding of CHB metabolism. Previously, we
      demonstrated that CHB was bioactivated to 1-chloro-3-buten-2-one (CBO) by alcohol
      dehydrogenase. However, CHB metabolism by cytochrome P450s has not been reported.
      Thus, in the present study, CHB metabolism by rat liver microsomes was
      investigated. The results showed that CHB was converted to 1-chloro-3,4-epoxy-2
      butanol (CEB) and CBO. 4-Methylpyrazole, a cytochrome P450 2E1-specific
      inhibitor, inhibited the formation of both CEB and CBO, while 1-benzylimidazole,
      a generic cytochrome P450 inhibitor, completely abolished the formation of CEB
      and CBO, suggesting that CHB metabolism was mediated by cytochrome P450s. Because
      the molecules have two chiral centers, CEB was detected as two stereoisomers,
      which were designated D-CEB and M-CEB, and were characterized as (2S,3R)-/(2R,3S)
      CEB and (2R,3R)-/(2S,3S)-CEB, respectively. The amounts of M-CEB were more than
      those of D-CEB by 50-80%. The amounts of CEB and CBO increased linearly over time
      from 10 (or 20 min for CBO) to 50 min. CHB metabolism followed Michaelis-Menten
      kinetics; the Km and Vmax values were determined to be 6.4 +/- 0.7 mM and 0.10 +/
      0.01 nmol/min/mg protein for D-CEB, 4.2 +/- 0.5 mM and 0.16 +/- 0.01 nmol/min/mg
      protein for M-CEB, and 4.0 +/- 0.5 mM and 4.6 +/- 0.5 nmol/min/mg protein for
      CBO, respectively. Thus, CBO was the dominant product of CHB metabolism.
      Moreover, CEB was genotoxic at >= 50 MUM as evaluated by the comet assay.
      Collectively, the data showed that CHB could be bioactivated to CEB and CBO by
      cytochrome P450s with CBO being the predominant product. Thus, the formation of
      CEB and CBO can be used as evidence of CHB production. The products may also play
      a role in toxicity of CHB.

PMID- 29329667
TI  - Gel-forming mucin interactome drives mucus viscoelasticity.
AB  - Mucus is a hydrogel that constitutes the first innate defense in all mammals. The
      main organic component of mucus, gel-forming mucins, forms a complex network
      through both reversible and irreversible interactions that drive mucus gel
      formation. Significant advances in the understanding of irreversible gel-forming
      mucins assembly have been made using recombinant protein approaches. However,
      little is known about the reversible interactions that may finely modulate mucus
      viscoelasticity, which can be characterized using rheology. This approach can be
      used to investigate both the nature of gel-forming mucins interactions and
      factors that influence hydrogel formation. This knowledge is directly relevant to
      the development of new drugs to modulate mucus viscoelasticity and to restore
      normal mucus functions in diseases such as in cystic fibrosis. The aim of the
      present review is to summarize the current knowledge about the relationship
      between the mucus protein matrix and its functions, with emphasis on mucus
      viscoelasticity.

PMID- 29329669
TI  - Prevalence and Predictors of Symptom Resolution and Functional Restoration in the
      Index Knee After Knee Arthroplasty: A Longitudinal Study.
AB  - OBJECTIVES: To determine the prevalence of a 1- to 2-year postsurgical pain-free
      state and pain plus symptom-free state as well as functional restoration after
      knee arthroplasty (KA) and to identify predictors of these outcomes. DESIGN:
      Cohort study. SETTING: Communities of 4 sites. PARTICIPANTS: Consecutive
      participants (N=383) who underwent KA on at least 1 knee during the first 8 years
      of the study (mean age, 67.95+/-8.5y; 61.4% women; n=235). INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: A composite pain score included the Western
      Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain scale and 2
      generic pain rating scales. Composite pain plus other symptoms scores included 3
      pain scales, a stiffness scale, and, in addition, the Knee injury and
      Osteoarthritis Outcome Score Symptoms scale. The WOMAC Function scale was used to
      quantify functional status. Prevalence estimates and predictors of a pain-free
      state, symptom-free state, and a fully functioning state were determined.
      RESULTS: A sample of 383 participants with KA was studied, and of these, 34.1%
      (95% confidence interval [CI], 29.3%-39.2%; n=131) had a composite score of 0 for
      pain. A total of 14.1% (95% CI, 10.8%-18.1%; n=54) had a composite score of 0,
      indicating a symptom-free state, whereas 29.0% (95% CI, 24.4%-34.0%; n=111)
      achieved a score of 0 on the WOMAC Function scale. CONCLUSIONS: The prevalence of
      complete pain relief was 34%, the prevalence of complete pain and symptom relief
      was 14%, and the prevalence of complete functional restoration was 29% after KA.
      Participants who are older and with lower (better) WOMAC Pain scores were more
      likely to be pain-free after surgery. These data collected from a community-based
      sample have the potential to inform clinicians screening patients for KA
      consultation in a shared decision-making discussion to better align patient
      expectations with the most likely outcome.

PMID- 29329670
TI  - Motor Skill Interventions in Children With Developmental Coordination Disorder: A
      Systematic Review and Meta-Analysis.
AB  - OBJECTIVES: To determine the characteristics and effectiveness of motor skill
      interventions in children with developmental coordination disorder (DCD) and to
      identify potential moderators of training effects using meta-analysis. DATA
      SOURCES: A search was conducted in 6 databases (CINAHL Plus, Cochrane Library,
      Embase, ERIC, PsycINFO, and PubMed) for articles published between 1995 and
      August 2017 using search items which were grouped into 3 components (motor skill
      interventions, DCD, and age group of interest). STUDY SELECTION: Studies were
      included if they recruited children 3 to 17 years of age with DCD, reported
      performance of motor-related skills as outcomes, were published in peer-reviewed
      journals, and were written in English. Qualitative synthesis was conducted for
      all included studies. Quantitative synthesis (meta-analysis) was only conducted
      for studies using a (quasi) randomized controlled trial design. DATA EXTRACTION:
      Methodology, participant characteristics, intervention components, outcomes, and
      statistically significant training effects of each included study were extracted.
      DATA SYNTHESIS: Sixty-six studies met the inclusion criteria with 18 of the
      studies eligible for meta-analysis. Motor performance and cognitive, emotional,
      and other psychological factors were the most common outcomes. Other 3 outcome
      categories included perceptions and/or satisfaction regarding the children's
      improvement from significant others, physical fitness, and physical activity and
      participation. Immediate and moderate training effects were found for motor
      performance (Hedges g=.63; 95% confidence interval [CI], .31-.94; P<.001) and
      cognitive, emotional, and other psychological factors (Hedges g=0.65; 95% CI,
      0.25-1.04; P=.001). Additionally, dose (minutes in total) and frequency of the
      intervention were significant moderators of training effect on motor performance.
      CONCLUSIONS: Motor skill interventions are effective in improving motor
      competence and performance on cognitive, emotional, and other psychological
      aspects in children with DCD in the short term. These effects are more robust in
      interventions using a large training dose and a practicing schedule of high
      frequency.

PMID- 29329668
TI  - Helicobacter pylori induces direct activation of the lymphotoxin beta receptor
      and non-canonical nuclear factor-kappa B signaling.
AB  - The pathogen Helicobacter pylori, which infects half of the world's population,
      is a major risk factor for the development of gastric diseases including chronic
      gastritis and gastric cancer. Among H. pylori's virulence factors is the
      cytotoxin-associated gene pathogenicity island (cagPAI), which encodes for a type
      IV secretion system (T4SS). The T4SS induces fast canonical nuclear factor-kappa
      B (NF-kappaB) signaling, a major factor increasing inflammation, supressing
      apoptotic cell death and thereby promoting the development of neoplasia. However,
      H. pylori's capability to mediate fast non-canonical NF-kappaB signaling is
      unresolved, despite a contribution of non-canonical NF-kappaB signaling to
      gastric cancer has been suggested. We analyzed signaling elements within non
      canonical NF-kappaB in response to H. pylori in epithelial cell lines by
      immunoprecipitation, immunoblot, electrophoretic mobility shift assay and RNA
      interference knockdown. In addition, tissue samples of H. pylori-infected
      patients were investigated by immunohistochemistry. Here, we provide evidence for
      a T4SS-dependent direct activation of non-canonical NF-kappaB signaling. We
      identified the lymphotoxin beta receptor (LTbetaR) to elicit the fast release of
      NF-kappaB inducing kinase (NIK) from the receptor complex leading to non
      canonical NF-kappaB signaling. Further, NIK expression was increased in human
      biopsies of H. pylori-associated gastritis. Thus, NIK could represent a novel
      target to reduce Helicobacter pylori-induced gastric inflammation and pathology.

PMID- 29329671
TI  - Localizing two acoustic emission sources simultaneously using beamforming and
      singular value decomposition.
AB  - Aiming at the issue that the weak AE source is easy to be lost when localizing
      simultaneous two acoustic emission (AE) sources by the beamforming method (BFM),
      a novel method is developed based on beamforming and singular value decomposition
      (SVD). Firstly, the AE data and propagation characteristics of the two
      simultaneous AE sources with different frequency, different magnitude and
      different positions are obtained, and localization results by directly using the
      beamforming are investigated. Then SVD method is introduced to pre-process the
      signals from AE sources and solve the problem of missing location. Finally, the
      method is verified on a steel plate by AE experiment. The results show that the
      localization method based on SVD-beamforming method (SVD-BFM) can effectively
      locate the simultaneous double AE sources.

PMID- 29329672
TI  - There are probably no differences in arrest of white-spot lesions and plaque
      composition between remineralizing and nonfluoridated toothpastes.

PMID- 29329673
TI  - Use of naproxen before in-office tooth bleaching may result in a small decrease
      in tooth sensitivity during and immediately after the procedure.

PMID- 29329674
TI  - Long-term esthetic outcomes of patients with cleft lip and palate have improved
      over time.

PMID- 29329675
TI  - Root canal retreatment with Thermafil as an obturator seems to have acceptable
      survival after 5 years.

PMID- 29329676
TI  - A mixed linear model controlling for case underascertainment across multiple
      cancer registries estimated time trends in survival.
AB  - OBJECTIVES: Large temporal and geographical variation in survival rates estimated
      from epidemiological cancer registries coupled with heterogeneity in death
      certificate only (DCO) notifications makes it difficult to interpret trends in
      survival. The aim of our study is to introduce a method for estimating such
      trends while accounting for heterogeneity in DCO notifications in a cancer site
      specific manner. STUDY DESIGN AND SETTING: We used the data of 4.0 million cancer
      cases notified in 14 German epidemiological cancer registries. Annual 5-year
      relative survival rates from 2002 through 2013 were estimated, and proportions of
      DCO notifications were recorded. "DCO-excluded" survival rates were regressed on
      DCO proportions and calendar years using a mixed linear model with cancer
      registry as a random effect. Based on this model, trends in survival rates were
      estimated for Germany at 0% DCO. RESULTS: For most cancer sites and age groups,
      we estimated significant positive trends in survival. Age-standardized survival
      for all cancers combined increased by 7.1% units for women and 10.8% units for
      men. CONCLUSION: The described method could be used to estimate trends in cancer
      survival based on the data from epidemiological cancer registries with differing
      DCO proportions and with changing DCO proportions over time.

PMID- 29329677
TI  - Living systematic reviews, not only for clinical (placebo) research.

PMID- 29329678
TI  - Apelin-13 ameliorates cognitive impairments in 6-hydroxydopamine-induced
      substantia nigra lesion in rats.
AB  - Although Parkinson's disease (PD) is well known with its motor deficits, the
      patients often suffer from cognitive dysfunction. Apelin, as the endogenous
      ligand of the APJ receptor, is found in several brain regions such as substantia
      nigra and mesolimbic pathway. However, the role of apelin in cognition and
      cognitive disorders has not been fully clarified. In this study the effects of
      apelin-13 were investigated on cognitive disorders in rat Parkinsonism
      experimental model. 6-hydroxydopamine (6-OHDA) was administrated into the
      substantia nigra. Apelin-13 (1, 2 and 3MUg/rat) was administered into the
      substantia nigra one week after the 6-OHDA injection. Morris water maze (MWM),
      object location and novel object recognition tests were performed one month after
      the apelin injection. 6-OHDA-treated animals showed a significant impairment in
      cognitive functions which was revealed by the increased in the escape latency and
      traveled distance in MWM test and decreased in the exploration index in novel
      object recognition and object location tasks. Apelin-13 (3MUg/rat) significantly
      attenuates the mentioned cognitive impairments in 6-OHDA-treated animals. In
      conclusion, the data support the pro-cognitive property of apelin-13 in 6-OHDA
      induced cognitive deficit and provided a new pharmacological aspect of the
      neuropeptide apelin.

PMID- 29329679
TI  - Standardization of a fast and effective method for the generation and detection
      of platelet-derived microparticles by a flow cytometer.
AB  - The Flow Cytometry is the principal method used to measure platelet-derived
      microparticles (PDMPs), by fluorescent properties analysis. PDMPs (0.1-1.0 MUm)
      are abundant in circulation, accounting for approximately 90% of the
      microparticles and are associated with Cardiovascular Disease, the leading cause
      of death in the world.

PMID- 29329680
TI  - Correlation of severity of chronic obstructive pulmonary disease with potential
      biomarkers.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a non-specific
      inflammation, which involves the airways, lung parenchyma and pulmonary vessels.
      The inflammation causes the activation of inflammatory cells and the release of
      various inflammatory mediators such as interleukin-1 beta, interleukin-6 and
      tumor necrosis factor alpha (TNF-a). The present study was designed to assess the
      serum cytokines [Interleukin-1beta (IL-1beta), Interleukin-6 (IL-6), Tumor
      necrosis factor-alpha (TNF-alpha)] levels in chronic obstructive pulmonary
      disease (COPD) patients and they were correlated with severity of disease by
      spirometric measurements. MATERIALS AND METHODS: A total of 384 COPD patients and
      50 healthy controls were enrolled in this study. The COPD patients were divided
      according to gold stages ie: mild, moderate, severe and very severe. 5 ml of
      venous blood samples were taken from all participants and it was collected in a
      test tube containing anticoagulant and then centrifuged at 3000 rpm for 10 min.
      Serum was separated and used to measure the amount of TNF-alpha, il-1beta, and IL
      6. Spirometry was performed according to the criteria set by the Gold 2012
      RESULTS: Tnf-alpha (pg/ml), IL-6 (pg/ml), IL-1beta (pg/ml) serum levels in COPD
      patients and healthy controls subjects were measured. Tnf-alpha and IL-6 serum
      levels were significantly (<0.001) higher in COPD patients compared to healthy
      control subjects. Likewise, IL-1 beta levels were also significantly (p-value =
      0.022) higher in COPD patients compared to healthy control subjects. The
      distribution of Tnf-alpha, IL-6, IL-1beta (pg/ml) serum levels in COPD patients
      in relation to GOLD grading. There was a significant (p < 0.001) difference in
      the level of TNF-alpha, IL-6 and IL-1beta (pg/ml) among the severity of COPD. The
      posthoc analysis revealed that the TNF-alpha was significantly (p < 0.05) higher
      among the than mild, moderate, severe and very severe COPD patients. A similar
      observation was also found for IL-6. However, IL-6 was significantly (p < 0.05)
      higher among mild, moderate, severe and very severe COPD patients. There was
      significant (p = < 0.0001) difference in the level of IL-1beta in the different
      severity of COPD. The posthoc comparison test showed that IL-1beta levels were
      significantly (p < 0.05) higher among the mild, moderate, severe and very severe
      COPD patients. CONCLUSION: The present study signifies that the levels of TNF
      alpha, IL-1beta, and IL-6 are directly proportional to the post-bronchodilator
      FEV1 percentage. Results provide population-based evidence that COPD is
      independently associated with low-grade systemic inflammation, with a different
      inflammatory pattern than that observed in healthy subjects. Overall, these
      results identify a novel systemic inflammatory COPD phenotype that may be the
      target of specific research and treatment.

PMID- 29329681
TI  - Expanding the genetic profile of Hay-Wells syndrome.

PMID- 29329682
TI  - Feline coronavirus: Insights into viral pathogenesis based on the spike protein
      structure and function.
AB  - Feline coronavirus (FCoV) is an etiological agent that causes a benign enteric
      illness and the fatal systemic disease feline infectious peritonitis (FIP). The
      FCoV spike (S) protein is considered the viral regulator for binding and entry to
      the cell. This protein is also involved in FCoV tropism and virulence, as well as
      in the switch from enteric disease to FIP. This regulation is carried out by
      spike's major functions: receptor binding and virus-cell membrane fusion. In this
      review, we address important aspects in FCoV genetics, replication and
      pathogenesis, focusing on the role of S. To better understand this, FCoV S
      protein models were constructed, based on the human coronavirus NL63 (HCoV-NL63)
      S structure. We describe the specific structural characteristics of the FCoV S,
      in comparison with other coronavirus spikes. We also revise the biochemical
      events needed for FCoV S activation and its relation to the structural features
      of the protein.

PMID- 29329683
TI  - Respiratory disease in ball pythons (Python regius) experimentally infected with
      ball python nidovirus.
AB  - Circumstantial evidence has linked a new group of nidoviruses with respiratory
      disease in pythons, lizards, and cattle. We conducted experimental infections in
      ball pythons (Python regius) to test the hypothesis that ball python nidovirus
      (BPNV) infection results in respiratory disease. Three ball pythons were
      inoculated orally and intratracheally with cell culture isolated BPNV and two
      were sham inoculated. Antemortem choanal, oroesophageal, and cloacal swabs and
      postmortem tissues of infected snakes were positive for viral RNA, protein, and
      infectious virus by qRT-PCR, immunohistochemistry, western blot and virus
      isolation. Clinical signs included oral mucosal reddening, abundant mucus
      secretions, open-mouthed breathing, and anorexia. Histologic lesions included
      chronic-active mucinous rhinitis, stomatitis, tracheitis, esophagitis and
      proliferative interstitial pneumonia. Control snakes remained negative and free
      of clinical signs throughout the experiment. Our findings establish a causal
      relationship between nidovirus infection and respiratory disease in ball pythons
      and shed light on disease progression and transmission.

PMID- 29329685
TI  - Association of provider recommendation and offer and influenza vaccination among
      adults aged >=18 years - United States.
AB  - BACKGROUND: Influenza vaccination has been recommended for all persons aged >=6
      months since 2010. METHODS: Data from the 2016 National Internet Flu Survey were
      analyzed to assess provider vaccination recommendations and early influenza
      vaccination during the 2016-17 season among adults aged >=18 years. Predictive
      marginals from a multivariable logistic regression model were used to identify
      factors independently associated with early vaccine uptake by provider
      vaccination recommendation status. RESULTS: Overall, 24.0% visited a provider who
      both recommended and offered influenza vaccination, 9.0% visited a provider who
      only recommended but did not offer, 25.1% visited a provider who neither
      recommended nor offered, and 41.9% did not visit a doctor from July 1 through
      date of interview. Adults who reported that a provider both recommended and
      offered vaccine had significantly higher vaccination coverage (66.6%) compared
      with those who reported that a provider only recommended but did not offer
      (48.4%), those who neither received recommendation nor offer (32.0%), and those
      who did not visit a doctor during the vaccination period (28.8%). Results of
      multivariable logistic regression indicated that having received a provider
      recommendation, with or without an offer for vaccination, was significantly
      associated with higher vaccination coverage after controlling for demographic and
      access-to-care factors. CONCLUSIONS: Provider recommendation was significantly
      associated with influenza vaccination. However, overall, 67.0% of adults did not
      visit a doctor during the vaccination period or did visit a doctor but did not
      receive a provider recommendation. Evidence-based strategies such as client
      reminder/recall, standing orders, provider reminders, or health systems
      interventions in combination should be undertaken to improve provider
      recommendation and influenza vaccination coverage. Other factors significantly
      associated with a higher level of influenza vaccination included age >=50 years,
      being Hispanic, having a college or higher education, having a usual place for
      medical care, and having public health insurance.

PMID- 29329684
TI  - Impact of seasonal influenza vaccination in the presence of vaccine interference.
AB  - BACKGROUND: Annual influenza vaccination is a key to preventing widespread
      influenza infections. Recent reports of influenza vaccine effectiveness (VE)
      indicate that vaccination in prior years may reduce VE in the current season,
      suggesting vaccine interference. The purpose of this study is to evaluate the
      potential effect of repeat influenza vaccinations in the presence of vaccine
      interference. METHODS: Using literature-based parameters, an age-structured
      influenza equation-based transmission model was used to determine the optimal
      vaccination strategy, while considering the effect of varying levels of
      interference. RESULTS: The model shows that, even in the presence of vaccine
      interference, revaccination reduces the influenza attack rate and provides
      individual benefits. Specifically, annual vaccination is a favored strategy over
      vaccination in alternate years, as long as the level of residual protection is
      less than 58% or vaccine interference effect is minimal. Furthermore, the
      negative impact of vaccine interference may be offset by increased vaccine
      coverage levels. CONCLUSIONS: Even in the presence of potential vaccine
      interference, our work provides a population-level perspective on the potential
      merits of repeated influenza vaccination. This is because repeat vaccination
      groups had lower attack rates than groups that omitted the second vaccination
      unless vaccine interference was at very high, perhaps implausible, levels.

PMID- 29329686
TI  - Highlighting priority areas for bovine viral diarrhea control in Italy: A
      phylogeographic approach.
AB  - The prevalence and genetic diversity of bovine viral diarrhea virus (BVDV) in a
      geographic area are largely influenced by live animal trade and management
      practices. Despite control and eradication programs currently underway in several
      European countries, the risk of BVDV spread within and among countries is still
      present. BVDV-1 is the predominant type circulating in European cattle
      population. In this study, a phylogeographic analysis was applied to the BVDV-1
      highest prevalent subtypes in Italy to reconstruct the origin and spatial
      temporal distribution and to trace main viral flows between different locations
      to highlight priority areas for BVDV control. A comprehensive dataset of BVDV-1b
      (n = 173) and 1e (n = 172) 5' UTR sequences was analysed, including both novel
      and published sequences from Italy and from European countries bordering and/or
      with commercial cattle flows with Italy. A common phylogeographic pattern was
      observed for BVDV-1b and 1e subtypes: interspersion from multiple Italian areas
      and European countries was widespread until the end of the last century, whereas
      significant local clusters were observed starting from 2000. These findings
      support a continuous viral flow among different areas over long time scales with
      no evidence of significant geographical structure, while local transmission
      networks are limited to more recent years. Northern Italy has been confirmed as
      the area of origin of the main clades of both BVDV subtypes at national level,
      acting both as a crucial area for introduction and a maintenance source for other
      areas. Piedmont, Central and Southern Italian regions contributed to limited
      geographical distribution and local BVDV-1b and 1e persistence. On the whole,
      priority control measures for BVDV-1b and 1e in Italy should be focused on: i)
      implementation of BVDV systematic control in all Northern Italian regions to
      break the viral flow from larger to smaller animal populations; and ii) breaking
      the dynamics of infections in regions with self-maintenance of BVDV by voluntary
      control programs.

PMID- 29329688
TI  - Motorizing and Optimizing Ultrasound Strain Elastography for Detection of
      Intrauterine Growth Restriction Pregnancies.
AB  - Intrauterine growth restriction is a prevalent disease in pregnancy in which
      placental insufficiency leads to 5 to 10 times higher mortality and lifelong
      morbidities. The current detection rate is poor, and recently, ultrasound strain
      elastography (USEL) was proposed as a new diagnostic technique. Currently,
      placental USEL uses maternal subcutaneous fat as the reference layer, but this is
      not ideal as fat tissue stiffness can vary widely between subjects. Current USEL
      also uses manual palpation, and under different compression depths and rates,
      viscoelastic tissues such as placenta can yield different stiffness results. In
      the study described here, we strove to improve placental USEL by (i) using an
      external polymeric pad of known stiffness as the reference layer and (ii)
      adopting motorized control of the transducer during USEL to standardize palpation
      motion. Results indicated that motorized USEL reduced measurement variability by
      67% compared with freehand USEL. Satisfactory and statistically significant
      correlations between USEL measurements and mechanical testing validation results
      were obtained for our new USEL protocol. Placental tissues were found to be non
      linear and viscoelastic in nature and, thus, differed in stiffness at different
      compression rates and depths. Our study also revealed that there was a specific
      compression depth and rate during USEL that provided better correlation to
      mechanical testing, and should be considered in clinical placental USEL.

PMID- 29329690
TI  - Author's Response.

PMID- 29329689
TI  - Pediatric obesity: Current concepts.
AB  - This discussion reflects on concepts of obesity in children and adolescents in
      the early 21st century. It includes reflections on its history, definition,
      epidemiology, diagnostic perspectives, psychosocial considerations,
      musculoskeletal complications, endocrine complications and principles of
      management. In addition to emphasis on diet and exercise, research and clinical
      applications in the second decade of the 21st century emphasize the increasing
      use of pharmacotherapy and bariatric surgery for adolescent and adult populations
      with critical problems of overweight and obesity. We conclude with a discussion
      of future directions in pediatric obesity management.

PMID- 29329691
TI  - Communication Disparity Between the Bereaved and Others: What Hurts Them and What
      Is Unhelpful? A Nationwide Study of the Cancer Bereaved.
AB  - CONTEXT: The importance of communication between the cancer bereaved and others
      has been emphasized, but little is known about the more problematic aspects of
      this communication such as "unhelpful communication." OBJECTIVES: The aim of this
      study was to establish which types of communication are perceived by the bereaved
      to be unhelpful. METHODS: We conducted a cross-sectional, anonymous, nationwide
      survey at 103 certified hospice facilities/palliative care units in Japan.
      RESULTS: A total of 630 (63%) bereaved responded. Over 60% of the bereaved
      experiencing such communication considered it to be unhelpful, with the most
      unhelpful communication being "They emphasized the positive aspects of death."
      Thirteen items related to communication were separated into two factors ("advice
      for recovery" and "comments on cancer") by factor analysis. "Comments on cancer"
      were more unhelpful to them and were more often provided by those around them.
      With regard to "advice for recovery," losing a spouse was a stronger predictor
      with a higher odds ratio for communication distress than losing a parent (odds
      ratio, 5.34; 95% CI, 1.63-17.57). CONCLUSION: A number of the bereaved have
      experienced unhelpful communication regarding advice on dealing with bereavement
      and cancer. To prevent putting an unnecessary burden on the bereaved with such
      unhelpful communication, it is essential to understand problematic aspects. Even
      when people have no intention of hurting the bereaved, some communication may do
      so. Communication with the bereaved is also a core clinical skill required by
      health professionals, and further efforts are required to support the grieving
      process.

PMID- 29329692
TI  - Potential psychological & neural mechanisms in binge eating disorder:
      Implications for treatment.
AB  - Binge Eating Disorder (BED) is a newly-established eating disorder diagnosis in
      the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM
      5). Although systematic research on BED is in its infancy and many studies
      feature small samples, several observations emerge. First, we review diagnostic,
      developmental, and socio-demographic features of BED. Next, although BED and
      obesity are linked and frequently co-occur, we review data suggesting that BED is
      a distinct phenotype. Importantly, we take a mechanism-focused approach and
      propose four psychological processes with neurobiological bases that may uniquely
      differentiate BED from obesity: emotion reactivity, food-cue reactivity, food
      craving, and cognitive control. Further, we propose that interactions between
      impairments in cognitive control and increased emotional reactivity, food-cue
      reactivity, and craving may underlie emotion dysregulation and promote binge
      eating. Consistently, neuroimaging studies point towards neural alterations in
      the response to rewards and to food specifically, and suggest preliminary links
      between impaired cognitive-control-related neural activity and binge eating.
      However, additional systematic work is required in this area. We conclude with a
      detailed review of treatment approaches to BED; specifically, we suggest that
      psychological and pharmacological treatments that target core mechanisms -
      including cognitive control and emotion/craving dysregulation - may be
      particularly effective.

PMID- 29329693
TI  - BOLD fMRI signal in stroke patients and its importance for prognosis in the
      subacute disease period - Preliminary report.
AB  - : Functional magnetic resonance imaging (fMRI) allows for the assessment of
      neuronal activity through the blood-level-dependent signal. The purpose of study
      was to evaluate the pattern of brain activity in fMRI in patients with ischemic
      stroke and to assess the potential relationship between the activity pattern and
      the neurological/functional status. METHODS: The fMRI was performed in patients
      up to 4th day of stroke. All the patients were analyzed according to NIHSS on 1st
      day and mRankin scale on 14th day of stroke, followed by analyzing of fMRI
      signal. RESULTS: The study enrolled 13 patients at a mean age of 64.3years. Eight
      (61.5%) showed cerebellar activation and 2 (15.38%)- insular activation. In those
      who scored 0-2 on mRankin scale, the most frequently observed activity was
      located in the regions: the M1, SMA and PMC in the stroke hemisphere and the
      cerebellum. In those cases, the non-stroke hemisphere was more frequently
      involved in the areas: the M1 and PMC. There was a tendency for a better
      prognosis in relation to age <65years and activation of the SMA in the stroke
      hemisphere. CONCLUSION: There are differences observed in the activation areas of
      the cerebral cortex both in the stroke and non-stroke hemispheres. More than half
      of the patients with hemispheric stroke but all with good outcome showed
      cerebellar activation. There is probable positive correlation between the BOLD
      signal size, young age, activation of supplementary motor area in stroke
      hemisphere and good functional status of patients in the subacute period of
      stroke.

PMID- 29329687
TI  - Bubble-Induced Color Doppler Feedback Correlates with Histotripsy-Induced
      Destruction of Structural Components in Liver Tissue.
AB  - Bubble-induced color Doppler (BCD) is a histotripsy-therapy monitoring technique
      that uses Doppler ultrasound to track the motion of residual cavitation nuclei
      that persist after the collapse of the histotripsy bubble cloud. In this study,
      BCD is used to monitor tissue fractionation during histotripsy tissue therapy,
      and the BCD signal is correlated with the destruction of structural and non
      structural components identified histologically to further understand how BCD
      monitors the extent of treatment. A 500-kHz, 112-element phased histotripsy array
      is used to generate approximately 6- * 6- * 7-mm lesions within ex vivo bovine
      liver tissue by scanning more than 219 locations with 30-1000 pulses per
      location. A 128-element L7-4 imaging probe is used to acquire BCD signals during
      all treatments. The BCD signal is then quantitatively analyzed using the time-to
      peak rebound velocity (tprv) metric. Using the Pearson correlation coefficient,
      the tprv is compared with histologic analytics of lesions generated by various
      numbers of pulses using a significance level of 0.001. Histologic analytics in
      this study include viable cell count, reticulin-stained type III collagen area
      and trichrome-stained type I collagen area. It is found that the tprv metric has
      a statistically significant correlation with the change in reticulin-stained type
      III collagen area with a Pearson correlation coefficient of -0.94 (p <0.001),
      indicating that changes in BCD are more likely because of destruction of the
      structural components of tissue.

PMID- 29329694
TI  - Management of Refractory Vasodilatory Shock.
AB  - Refractory shock is a lethal manifestation of cardiovascular failure defined by
      an inadequate hemodynamic response to high doses of vasopressor medications.
      Approximately 7% of critically ill patients will develop refractory shock, with
      short-term mortality exceeding 50%. Refractory vasodilatory shock develops from
      uncontrolled vasodilation and vascular hyporesponsiveness to endogenous
      vasoconstrictors, causing failure of physiologic vasoregulatory mechanisms.
      Standard approaches to the initial management of shock include fluid
      resuscitation and initiation of norepinephrine. When these measures are
      inadequate to restore BP, vasopressin or epinephrine can be added. Few randomized
      studies exist to guide clinical management and hemodynamic stabilization in
      patients who do not respond to this standard approach. Adjunctive therapies, such
      as hydrocortisone, thiamine, and ascorbic acid, may increase BP in severe shock
      and should be considered when combination vasopressor therapy is needed. Novel
      vasopressor agents, such as synthetic human angiotensin II, can increase BP and
      reduce the need for high doses of catecholamine vasopressors in severe or
      refractory vasodilatory shock. Few effective rescue therapies exist for
      established refractory shock, which emphasizes the importance of aggressive
      intervention before refractory shock develops, including the earlier initiation
      of rational combination vasopressor therapy. The present review discusses the
      diagnosis and management of refractory shock to offer guidance for management of
      this important clinical problem and to provide a framework for future research.

PMID- 29329695
TI  - A patient with pembrolizumab-induced fatal polymyositis.

PMID- 29329696
TI  - Pharmacokinetics partly explains the relationship between carcinoembryonic
      antigen level and survival of colorectal cancer patients treated with
      ramucirumab.

PMID- 29329698
TI  - Effect of combined exercise training on serum brain-derived neurotrophic factor,
      suppressors of cytokine signaling 1 and 3 in patients with multiple sclerosis.
AB  - BACKGROUND: Suppressors of cytokine signaling (SOCS) and brain-derived
      neurotrophic factor (BDNF) are important immunologic, and neurotrophic factors
      for MS pathogenesis. The impact of exercise on these factors is yet to be fully
      elucidated in patients with MS. OBJECTIVE: The primary aim of this study is to
      investigate the effect of 8-week combined exercise training on serum
      concentrations of SOCS1, SOCS3, and BDNF. The secondary aim is to determine the
      effects of combined exercise training on balance, functional exercise capacity,
      and fatigue in patients with MS. METHODS: Serum SOCS1, SOCS3, and BDNF levels
      were assessed in 36 MS patients and 18 healthy individuals. In addition, balance,
      functional exercise capacity, and fatigue were assessed in the patients with MS.
      The patients were randomly divided into the combined exercise group (MS-EX, n:18)
      and the control group (MS-C, n:18). MS-EX received an 8-week combined exercise
      training. RESULTS: The serum SOCS1, SOCS3, and BDNF levels were similar in the MS
      patients and healthy control (HC). In MS-EX, the serum BDNF level, balance,
      functional exercise capacity, and fatigue improved after 8weeks (p<0.05), but the
      serum SOCS1, and SOCS3 levels did not change significantly (p>0.05). In MS-C, the
      serum SOCS1 level, and fatigue increased significantly after 8weeks (p<0.05), but
      serum SOCS3, BDNF, balance and functional exercise capacity did not change
      (p>0.05). CONCLUSIONS: In summary, the combined exercise training improved BDNF,
      and physical performance in patients with MS. But, future studies are needed to
      clarify the role of SOCS proteins in MS pathogenesis and the effect of exercise
      on SOCS.

PMID- 29329697
TI  - Ageing perceptions and non-adherence to aromatase inhibitors among breast cancer
      survivors.
AB  - PURPOSE: Aromatase inhibitors (AIs) are a potentially life-saving treatment for
      breast cancer survivors, yet poor adherence to treatment is a prevalent problem.
      A common adverse effect of AI treatment is arthralgia, which is identified by
      survivors as a major reason for treatment discontinuation. Women who experience
      arthralgia on AIs often report feeling they have aged rapidly while on the
      treatment. In the present study, we examined whether arthralgia-associated ageing
      perceptions predicted non-adherence. PATIENTS AND METHODS: We conducted a
      prospective cohort study among women with stage I-III breast cancer, who were on
      an AI and completed the Penn Arthralgia Aging Scale within 2 years of AI
      initiation. Adherence data were abstracted from medical charts by trained raters.
      Cox proportional hazard analysis was used to determine the relationship between
      ageing perceptions and time to non-adherence. All analyses included adjustments
      for joint pain severity. RESULTS: Among 509 participants, 144 (28.3%) were non
      adherent. As hypothesised, women with high levels of ageing perceptions were at
      greater risk of non-adherence than women with low levels of ageing perceptions
      (adjusted hazard ratio [HR], 1.71; 95% confidence interval [CI], 1.10-2.67; p =
      .02). High levels of depressive symptoms were also uniquely associated with
      increased risk of non-adherence (adjusted HR, 1.63; 95% CI, 1.03-2.59; p = .04).
      CONCLUSION: Perceptions of ageing related to arthralgia and depressive symptoms
      predicted non-adherence to AIs. These findings suggest that interventions that
      address negative beliefs about ageing due to AI-related arthralgia and depressive
      mood can potentially improve rates of adherence to AIs.

PMID- 29329699
TI  - Soluble CD40 ligand disrupts the blood-brain barrier and exacerbates inflammation
      in experimental autoimmune encephalomyelitis.
AB  - Serum soluble CD40 ligand (sCD40L) has been reported to positively correlate with
      the albumin quotient, a marker of blood-brain barrier (BBB) breakdown, in
      patients with multiple sclerosis (MS). To clarify the mechanisms of sCD40L in MS
      pathophysiology, sCD40L was administered to experimental autoimmune
      encephalomyelitis (EAE) mice and a human brain microvascular endothelial cell
      (HBMEC)-based BBB model. The high-dose sCD40L group showed a worse EAE score than
      the low-dose and control groups. BBB permeability was increased by administering
      sCD40L in a HBMEC-based BBB model. Thus, sCD40L induces more severe inflammation
      in the central nervous system by disrupting the BBB.

PMID- 29329700
TI  - [A Listeria breast abscess in a man].
AB  - INTRODUCTION: Listeriosis is a food-borne illness leading to bacteriemia or
      central nervous system infection especially in pregnant women or high-risk
      patients. It is rarely a localized infection. Breast contamination has rarely
      been reported in lactating women. We report a breast abscess in man. CASE REPORT:
      A 80 year old man, hypertensive and arrhythmic, was explored for weakness and
      dehydration. Type 2 diabetes and chronic lymphocytic leukemia were diagnosed.
      Clinical examination disclosed a breast abcess related to L monocytogenes
      infection. Histopathological study also revealed a breast subcutaneous
      infiltration by chronic lymphocytic leukemia. CONCLUSION: Listeriosis sometimes
      uncover an unknown immunosuppression, especially in the elderly. Breast is a non
      sterile tissue containing a stable microbiome partly from digestive origin. It
      can thereby be contaminated by Listeria. The specific cutaneous infiltrate of
      chronic lymphocytic leukemia can create the conditions for a local infection.

PMID- 29329701
TI  - Automatic information extraction from unstructured mammography reports using
      distributed semantics.
AB  - To date, the methods developed for automated extraction of information from
      radiology reports are mainly rule-based or dictionary-based, and, therefore,
      require substantial manual effort to build these systems. Recent efforts to
      develop automated systems for entity detection have been undertaken, but little
      work has been done to automatically extract relations and their associated named
      entities in narrative radiology reports that have comparable accuracy to rule
      based methods. Our goal is to extract relations in a unsupervised way from
      radiology reports without specifying prior domain knowledge. We propose a hybrid
      approach for information extraction that combines dependency-based parse tree
      with distributed semantics for generating structured information frames about
      particular findings/abnormalities from the free-text mammography reports. The
      proposed IE system obtains a F1-score of 0.94 in terms of completeness of the
      content in the information frames, which outperforms a state-of-the-art rule
      based system in this domain by a significant margin. The proposed system can be
      leveraged in a variety of applications, such as decision support and information
      retrieval, and may also easily scale to other radiology domains, since there is
      no need to tune the system with hand-crafted information extraction rules.

PMID- 29329702
TI  - Ten factors to consider when developing usability scenarios and tasks for health
      information technology.
AB  - The quality of usability testing is highly dependent upon the associated
      usability scenarios. To promote usability testing as part of electronic health
      record (EHR) certification, the Office of the National Coordinator (ONC) for
      Health Information Technology requires that vendors test specific capabilities of
      EHRs with clinical end-users and report their usability testing process -
      including the test scenarios used - along with the results. The ONC outlines
      basic expectations for usability testing, but there is little guidance in
      usability texts or scientific literature on how to develop usability scenarios
      for healthcare applications. The objective of this article is to outline key
      factors to consider when developing usability scenarios and tasks to evaluate
      computer-interface based health information technologies. To achieve this goal,
      we draw upon a decade of our experience conducting usability tests with a variety
      of healthcare applications and a wide range of end-users, to include healthcare
      professionals as well as patients. We discuss 10 key factors that influence
      scenario development: objectives of usability testing; roles of end-user(s);
      target performance goals; evaluation time constraints; clinical focus; fidelity;
      scenario-related bias and confounders; embedded probes; minimize risks to end
      users; and healthcare related outcome measures. For each factor, we present an
      illustrative example. This article is intended to aid usability researchers and
      practitioners in their efforts to advance health information technologies. The
      article provides broad guidance on usability scenario development and can be
      applied to a wide range of clinical information systems and applications.

PMID- 29329703
TI  - Highly-sensitive microRNA detection based on bio-bar-code assay and catalytic
      hairpin assembly two-stage amplification.
AB  - Herein, a highly-sensitive microRNA (miRNA) detection strategy was developed by
      combining bio-bar-code assay (BBA) with catalytic hairpin assembly (CHA). In the
      proposed system, two nanoprobes of magnetic nanoparticles functionalized with DNA
      probes (MNPs-DNA) and gold nanoparticles with numerous barcode DNA (AuNPs-DNA)
      were designed. In the presence of target miRNA, the MNP-DNA and AuNP-DNA
      hybridized with target miRNA to form a "sandwich" structure. After "sandwich"
      structures were separated from the solution by the magnetic field and
      dehybridized by high temperature, the barcode DNA sequences were released by
      dissolving AuNPs. The released barcode DNA sequences triggered the toehold strand
      displacement assembly of two hairpin probes, leading to recycle of barcode DNA
      sequences and producing numerous fluorescent CHA products for miRNA detection.
      Under the optimal experimental conditions, the proposed two-stage amplification
      system could sensitively detect target miRNA ranging from 10 pM to 10 aM with a
      limit of detection (LOD) down to 97.9 zM. It displayed good capability to
      discriminate single base and three bases mismatch due to the unique sandwich
      structure. Notably, it presented good feasibility for selective multiplexed
      detection of various combinations of synthetic miRNA sequences and miRNAs
      extracted from different cell lysates, which were in agreement with the
      traditional polymerase chain reaction analysis. The two-stage amplification
      strategy may be significant implication in the biological detection and clinical
      diagnosis.

PMID- 29329704
TI  - A detailed electrochemical impedance spectroscopy study of a bismuth-film glassy
      carbon electrode for trace metal analysis.
AB  - A systematic electrochemical impedance spectroscopy (EIS) analysis at different
      potentials of an in situ-prepared bismuth-film glassy carbon electrode (BiFE) in
      0.1 M acetate buffer solution is reported. This electrode is employed in the
      square-wave anodic stripping voltammetry (SWASV) technique for the determination
      of trace amounts of the heavy metals Zn, Cd, and Pb. The method was first
      validated for detection limit, linear range, sensitivity, precision and accuracy
      to clearly prove the superior action of BiFE compared with the bare glassy carbon
      electrode (GCE). Next, in order to investigate the characteristics of this
      sensor, EIS measurements were carried out at slightly more negative potentials
      than the potentials at which each individual stripping signal is detected, after
      the deposition step at different deposition potentials. For comparison, EIS
      measurements were also performed at open circuit potential. The studied trace
      metal concentration range (5-20 ppb) did not significantly influence the
      capacitive and resistive behaviour of the BiFE which explains why the performance
      of this sensor is superior compared with the bare GCE. The higher sensitivity of
      the SWASV method for BiFE compared with the bare GCE was explained by the lower
      polarisation resistance values of the former. Moreover, the potential of zero
      charge was also determined, and an explanation whether the system is under
      kinetic- and/or diffusion-controlled process is given.

PMID- 29329706
TI  - Unattended reaction monitoring using an automated microfluidic sampler and on
      line liquid chromatography.
AB  - In-process sampling and analysis is an important aspect of monitoring kinetic
      profiles and impurity formation or rejection, both in development and during
      commercial manufacturing. In pharmaceutical process development, the technology
      of choice for a substantial portion of this analysis is high-performance liquid
      chromatography (HPLC). Traditionally, the sample extraction and preparation for
      reaction characterization have been performed manually. This can be time
      consuming, laborious, and impractical for long processes. Depending on the
      complexity of the sample preparation, there can be variability introduced by
      different analysts, and in some cases, the integrity of the sample can be
      compromised during handling. While there are commercial instruments available for
      on-line monitoring with HPLC, they lack capabilities in many key areas. Some do
      not provide integration of the sampling and analysis, while others afford limited
      flexibility in sample preparation. The current offerings provide a limited number
      of unit operations available for sample processing and no option for workflow
      customizability. This work describes development of a microfluidic automated
      program (MAP) which fully automates the sample extraction, manipulation, and on
      line LC analysis. The flexible system is controlled using an intuitive Microsoft
      Excel based user interface. The autonomous system is capable of unattended
      reaction monitoring that allows flexible unit operations and workflow
      customization to enable complex operations and on-line sample preparation. The
      automated system is shown to offer advantages over manual approaches in key areas
      while providing consistent and reproducible in-process data.

PMID- 29329705
TI  - Low-cost and disposable sensors for the simultaneous determination of coenzyme
      Q10 and alpha-lipoic acid using manganese (IV) oxide-modified screen-printed
      graphene electrodes.
AB  - In this work, for the first time, manganese (IV) oxide-modified screen-printed
      graphene electrodes (MnO2/SPGEs) were developed for the simultaneous
      electrochemical detection of coenzyme Q10 (CoQ10) and alpha-lipoic acid (ALA).
      This sensor exhibits attractive benefits such as simplicity, low production
      costs, and disposability. Cyclic voltammetry (CV) was used to characterize the
      electrochemical behavior of the analyte and investigate the capacitance and
      electroactive surface area of the unmodified and modified electrode surfaces. The
      electrochemical behavior of CoQ10 and ALA on MnO2/SPGEs was also discussed.
      Additionally, square wave anodic stripping voltammetry (SWASV) was used for the
      quantitative determination of CoQ10 and ALA. Under optimal conditions, the
      obtained signals are linear in the concentration range from 2.0 to 75.0 MUg mL-1
      for CoQ10 and 0.3-25.0 MUg mL-1 for ALA. The low limits of detection (LODs) were
      found to be 0.56 MUg mL-1 and 0.088 MUg mL-1 for CoQ10 and ALA, respectively.
      Moreover, we demonstrated the utility and applicability of the MnO2/SPGE sensor
      through simultaneous measurements of CoQ10 and ALA in dietary supplements. The
      sensor provides high accuracy measurements, exhibiting its high potential for
      practical applications.

PMID- 29329707
TI  - Simultaneous determination of 117 pesticides and 30 mycotoxins in raw coffee,
      without clean-up, by LC-ESI-MS/MS analysis.
AB  - This paper describes the optimization and validation of an acetonitrile based
      method for simultaneous extraction of multiple pesticides and mycotoxins from raw
      coffee beans followed by LC-ESI-MS/MS determination. Before extraction, the raw
      coffee samples were milled and then slurried with water. The slurried samples
      were spiked with two separate standard solutions, one containing 131 pesticides
      and a second with 35 mycotoxins, which were divided into 3 groups of different
      relative concentration levels. Optimization of the QuEChERS approach included
      performance tests with acetonitrile acidified with acetic acid or formic acid,
      with or without buffer and with or without clean-up of the extracts before LC-ESI
      MS/MS analysis. For the clean-up step, seven d-SPE sorbents and their various
      mixtures were evaluated. After method optimization a complete validation study
      was carried out to ensure adequate performance of the extraction and
      chromatographic methods. The samples were spiked at 3 concentrations levels with
      both mycotoxins and pesticides (with 6 replicates at each level, n = 6) and then
      submitted to the extraction procedure. Before LC-ESI-MS/MS analysis, the
      acetonitrile extracts were diluted 2-fold with methanol, in order to improve the
      chromatographic performance of the early-eluting polar analytes. Calibration
      standard solutions were prepared in organic solvent and in blank coffee extract
      at 7 concentration levels and analyzed 6 times each. The method was assessed for
      accuracy (recovery %), precision (RSD%), selectivity, linearity (r2), limit of
      quantification (LOQ) and matrix effects (%).

PMID- 29329709
TI  - Characterization of singly and multiply PEGylated insulin isomers by reversed
      phase ultra-performance liquid chromatography interfaced with ion mobility mass
      spectrometry.
AB  - Conjugation of poly(ethylene glycol) (PEG) to protein drugs (PEGylation) is
      increasingly utilized in the biotherapeutics field because it improves
      significantly the drugs' circulatory half-life, solubility, and shelf-life. The
      activity of a PEGylated drug depends on the number, size, and location of the
      attached PEG chain(s). This study introduces a 2D separation approach, including
      reversed-phase ultra-performance liquid chromatography (RP-UPLC) and ion mobility
      mass spectrometry (IM-MS), in order to determine the structural properties of the
      conjugates, as demonstrated for a PEGylated insulin sample that was prepared by
      random amine PEGylation. The UPLC dimension allowed separation based on polarity.
      Electrospray ionization (ESI) of the eluates followed by in-source dissociation
      (ISD) truncated the PEG chains and created insulin fragments that provided site
      specific information based on whether they contained a marker at the potential
      conjugation sites. Separation of the latter fragments by size and charge in the
      orthogonal IM dimension (pseudo-4D UPLC-ISD-IM-MS approach) enabled clear
      detection and identification of the positional isomers formed upon PEGylation.
      The results showed a highly heterogeneous mixture of singly and multiply
      conjugated isomers plus unconjugated material. PEGylation was observed on all
      three possible attachment sites (epsilon-NH2 of LysB29, A- and B-chain N
      termini). Each PEGylation site was validated by analysis of the same product
      after disulfide bond cleavage, so that the PEGylated A- and B- chain could be
      individually characterized with the same pseudo-4D UPLC-ISD-IM-MS method.

PMID- 29329708
TI  - Detection of native proteins using solid-substrate electrospray ionization mass
      spectrometry with nonpolar solvents.
AB  - Detection of native proteins, particularly directly from raw biological samples,
      has been a challenging task for mass spectrometry. In this study, we demonstrated
      that solid-substrate electrospray ionization mass spectrometry with nonpolar
      solvents such as n-hexane could allow detection of native proteins and protein
      complexes directly from raw biological samples. Mechanistic study revealed that
      the process involved rapid vaporization of the nonpolar solvent, temperature
      reduction of substrate surface, condensation of water from the ambient air, and
      spray ionization of the condensed water with analytes under the electric field.
      The fine spray with water at low temperature allowed the technique to detect
      native proteins, even directly from viscous samples (e.g., egg white) and solid
      samples (e.g., bone marrow). This study sheds new insight into the sampling and
      ionization process of mass spectrometry and provides a technique of great
      potential for characterization of proteins.

PMID- 29329710
TI  - Hydride generation coupled with thioglycolic acid coated gold nanoparticles as
      simple and sensitive headspace colorimetric assay for visual detection of
      Sb(III).
AB  - Antimony (Sb) is a toxic element which causes different health problems including
      cardiac problems and lung cancer in humans, and its levels in surface water can
      be noticeably increased to 100 MUg/L typically in the proximity of anthropogenic
      sources. Thus, besides instrumental techniques, it is of great significance to
      develop a simple, sensitive and selective analytical method for direct analysis
      of Sb(III) at trace level without the need of any expensive and/or complicated
      instrumentations and sample preparation processes. Herein, a simple and sensitive
      headspace colorimetric assay was developed for the detection of Sb(III) by
      hydride generation coupled with thioglycolic acid functionalized gold
      nanoparticles (TGA-AuNPs). Sb(III) in the 30 mL sample solution was converted
      into its volatile form (SbH3) through hydride generation reaction and headspace
      extracted into 100 MUL chromogenic reagent, which contains methanol as extractant
      and TGA-AuNPs as nanosensors, leading to aggregation of TGA-AuNPs and therefore a
      red-to-blue color change. Parameters influencing the chromogenic and hydride
      generation reactions were optimized. Addition of 300 MUM ethylenediamine
      tetraacetic acid (EDTA) as masking agent largely suppressed the inferences from
      mercury and arsenic. The proposed method can tolerate at least 10-fold As(III)
      and 100-fold other metal ions including Hg(II). The detection limits were 6.0 and
      1.2 MUg/L Sb(III) by naked-eye and UV-Vis spectrometer, respectively, which meet
      the maximum admissible level in drinking water (6 MUg/L) set by the United States
      Environmental Protection Agency. The feasibility of the proposed method was
      demonstrated by rapid detection of Sb(III) in river water, lake water, ground
      water and sea water samples by naked-eye at a spiking level of 6 MUg/L Sb(III).

PMID- 29329711
TI  - Colorimetric logic gate for alkaline phosphatase based on copper (II)-based metal
      organic frameworks with peroxidase-like activity.
AB  - Nanozymes have been extensively exploited in the construction of colorimetric
      sensors in the past decade. However, as lack of specific recognition element,
      these sensors are mostly limited in the detection of hydrogen peroxide and its
      related agents. In this work, a colorimetric assay for the detection of alkaline
      phosphatase (ALP) activity was developed by employing copper (II)-based metal
      organic frameworks (Cu-MOFs) as peroxidase mimic and pyrophosphate (PPi) as
      recognition element. Benefiting from its intrinsic porosity, Cu-MOFs built from
      one-step self-assembly showed a superior catalytic activity over horseradish
      peroxidase. It was found that, in the presence of PPi, the catalytic activity of
      Cu-MOFs was greatly inhibited due to the ultrastrong binding ability of Cu2+ with
      PPi, and no colorimetric signal was recorded. However, after incubation with ALP,
      such negative behavior of PPi can be suppressed as the hydrolysis of PPi into
      orthophosphates (Pi) with low affinity to Cu2+, producing a colorimetric signal
      depending on ALP level. On this basis, a way for quantitative analysis of ALP
      activity was paved accordingly. Compared with previously reported ALP assays
      based on nanomaterials, this assay is simple, cost-effective and visualized,
      which not only allows highly sensitive analysis of ALP activity with a detection
      limit of 0.19 U/L, but also exhibits a good sensing performance in serum samples.
      Furthermore, based on the distinct colorimetric signals induced by PPi and ALP,
      an IMPLICATION logic gate was constructed. We hope that this study could provide
      a new insight for designing nanozyme-based highly specific colorimetric sensors.

PMID- 29329712
TI  - Risk Factors and Frequency of Ingrown Nails in Adult Diabetic Patients.
AB  - The present study evaluated the properties of nails, frequency of ingrown nails
      in patients with type 2 diabetes mellitus (DM), risk factors for developing
      ingrown nails, and effect of diabetic polyneuropathy and vasculopathy on the
      development and outcome of ingrown nails. Our 6-month epidemiologic prospective
      study included 300 patients with type 2 DM attending a DM outpatient clinic for
      routine examinations. The general characteristics and foot changes of the study
      population were investigated. Diabetic polyneuropathy and vasculopathy were
      evaluated using a biothesiometer, monofilament tests, and arterial Doppler
      ultrasonography. The frequency of ingrown nails was 13.6%. Multivariate analysis
      with logistic regression showed that body mass index (odds ratio [OR] 1.077, 95%
      confidence interval [CI] 1.007 to 1.15; p = .03), previous trauma (OR 2.828, 95%
      CI 1.017 to 7,867, p = .042), a weak dorsalis pedis pulse (OR 2.72, 95% CI 1.17
      to 6.30, p = .02), trimming type (OR 2.3, 95 CI 1.06 to 4.98), p = .35),
      onychogryphosis (OR 9.036, 95% CI 2.34 to 34.87, p = .001), and subungual
      hyperkeratosis (OR 4.3, 95% CI 1.99 to 9.3, p = .001) were predictive variables
      for ingrown nails in our population. The incidence of onychomycosis was
      significantly greater in patients with ingrown nails (p = .032) than in patients
      without ingrown nails. The nail curvature ratio was greater in the patients with
      ingrown nails than in the group with normal nails. Arterial Doppler ultrasound
      examinations showed peripheral arterial disease in 19 patients (46.9%) with
      ingrown nails. The prevalence of ingrown nails was greater in the patients with
      DM than in the healthy population. Our results indicate that nail type, nail
      morphology, and diabetic vasculopathy affect the formation and evolution of
      ingrown nails.

PMID- 29329713
TI  - Baseline and pre-operative 1-year mortality risk factors in a cohort of 509 hip
      fracture patients consecutively admitted to a co-managed orthogeriatric unit
      (FONDA Cohort).
AB  - INTRODUCTION: The aim of this study was to determine the patient characteristics
      that predict 1-year mortality after a hip fracture (HF). METHODS: All patients
      admitted consecutively with fragility HF during 1 year in a co-managed
      orthogeriatric unit of a university hospital (FONDA cohort) were assesed.
      Baseline and admission demographic, clinical, functional, analytical and body
      composition variables were collected in the first 72 h after admission. A
      protocol designed to minimize the consequences of the HF was applied. One year
      after the fracture patients or their carers were contacted by telephone to
      ascertain their vital status. RESULTS: A total of 509 patients with a mean age of
      85.6 years were included. One-year mortality was 23.2%. The final multivariate
      model included 8 independent mortality risk factors: age >85 years, baseline
      functional impairment in basic activities of daily living, low body mass index,
      cognitive impairment, heart disease, low hand-grip strength, anaemia at
      admission, and secondary hyperparathyroidism associated with vitamin D
      deficiency. The association of several of these factors greatly increased
      mortality risk, with an OR (95% confidence interval [CI]) of 5.372 (3.227-8.806)
      in patients with 4 to 5 factors, and an OR (95% CI) of 11.097 (6.432-19.144) in
      those with 6 or more factors. CONCLUSIONS: In addition to previously known
      factors (such as age, impairment in basic activities of daily living, cognitive
      impairment, malnutrition and anaemia at admission), other factors, such as muscle
      strength and hyperparathyroidism associated with vitamin D deficiency, are
      associated with greater 1-year mortality after a HF.

PMID- 29329714
TI  - Mutation burden profile in familial Alzheimer's disease cases from India.
AB  - This study attempts to identify coding risk variants in genes previously
      implicated in Alzheimer's disease (AD) pathways, through whole-exome sequencing
      of subjects (N = 17) with AD, with a positive family history of dementia
      (familial AD). We attempted to evaluate the mutation burden in genes encoding
      amyloid precursor protein metabolism and previously linked to risk of dementias.
      Novel variants were identified in genes involved in amyloid precursor protein
      metabolism such as PSEN1 (chr 14:73653575, W161C, tgg > tgT), PLAT (chr
      8:42039530,G272R), and SORL1 (chr11:121414373,G601D). The mutation burden
      assessment of dementia-related genes for all 17 cases revealed 45 variants, which
      were either shared across subjects, or were present in just the 1 patient. The
      study shows that the clinical characteristics, and genetic correlates, obtained
      in this sample are broadly comparable to the other studies that have investigated
      familial forms of AD. Our study identifies rare deleterious genetic variations,
      in the coding region of genes involved in amyloid signaling, and other dementia
      associated pathways.

PMID- 29329715
TI  - Ten questions you should consider before submitting an article to a scientific
      journal.
AB  - Investigating involves not only knowing the research methods and designs; it
      involves knowing the strategies for disseminating and publishing the results in
      scientific journals. An investigation is considered complete when it is published
      and is disclosed to the scientific community. The publication of a manuscript is
      not simple, since it involves examination by a rigorous editorial process
      evaluator to ensure the scientific quality of the proposal. The objective of this
      article is to communicate to potential authors the main errors or deficiencies
      that typically and routinely explain the decision by the referees of scientific
      journals not to accept a scientific article. Based on the experience of the
      authors as referees of national and international journals in the field of
      nursing and health sciences, we have identified a total of 10 types or groups,
      which cover formulation errors, inconsistencies between different parts of the
      text, lack of structuring, imprecise language, information gaps, and the
      detection of relevant inaccuracies. The identification and analysis of these
      issues enables their prevention, and is of great use to future researchers in the
      dissemination of the results of their work to the scientific community. In short,
      the best publishing strategy is one that ensures the scientific quality of the
      work and spares no effort in avoiding the errors or deficiencies that referees
      routinely detect in the articles they evaluate.

PMID- 29329716
TI  - Gelatin- hydroxyapatite- calcium sulphate based biomaterial for long term
      sustained delivery of bone morphogenic protein-2 and zoledronic acid for
      increased bone formation: In-vitro and in-vivo carrier properties.
AB  - In this study, a novel macroporous composite biomaterial consisting of gelatin
      hydroxyapatite-calcium sulphate for delivery of bone morphogenic protein-2 (rhBMP
      2) and zoledronic acid (ZA) has been developed. The biomaterial scaffold has a
      porous structure and functionalization of the scaffold with rhBMP-2 induces
      osteogenic differentiation of MC3T3-e1 cells seen by a significant increase in
      biochemical and genetic markers of osteoblastic differentiation. In-vivo muscle
      pouch experiments showed higher mineralization using scaffold+rhBMP-2 when
      compared to an approved absorbable collagen sponge (ACS)+rhBMP-2 as verified by
      micro-CT. Co-delivery of rhBMP-2+ZA via the novel scaffold enabled a reduction in
      the effective rhBMP-2 doses. The presence of tartrate resistant acid phosphatase
      staining in the rhBMP-2 group indicates osteoclastic resorption, which could be
      stalled by adding ZA, which by speculation could explain the net increase in
      mineralization. The new scaffold allowed for slow release of rhBMP-2 in-vitro
      (3.3+/-0.1%) after 4weeks. Using single photon emission computed tomography
      (SPECT), the release kinetics of 125I-rhBMP-2 in-vivo was followed for 4weeks and
      a total of 65.3+/-15.2% 125I-rhBMP-2 was released from the scaffolds. In-vitro
      14C-ZA release curve shows an initial burst release on day 1 (8.8+/-0.7%)
      followed by a slow release during the following 4weeks (13+/-0.1%). In-vivo, an
      initial release of 43.2+/-7.6% of 14C-ZA was detected after 1day, after which the
      scaffold retained the remaining ZA during 4-weeks. Taken together, our results
      show that the developed biomaterial is an efficient carrier for spatio-temporal
      delivery of rhBMP-2 and ZA leading to increased bone formation compared to
      commercially available carrier for rhBMP-2.

PMID- 29329717
TI  - Erratum.

PMID- 29329718
TI  - Erratum.

PMID- 29329719
TI  - Regulatory Potential of the RNA Processing Machinery: Implications for Human
      Disease.
AB  - Splicing and nuclear export of mRNA are critical steps in the gene expression
      pathway. While RNA processing factors can perform general, essential functions
      for intron removal and bulk export of mRNA, emerging evidence highlights that the
      core RNA splicing and export machineries also display regulatory potential. Here,
      we discuss recent insights into how this regulatory potential can selectively
      alter gene expression and regulate important biological processes. We also
      highlight the participation of RNA processing pathways in the cellular response
      to DNA damage at multiple levels. These findings have important implications for
      the contribution of selective mRNA processing and export to the development of
      human cancers and neurodegenerative disorders.

PMID- 29329721
TI  - Quantifying fluctuation in glucose levels to identify early changes in glucose
      homeostasis in cystic fibrosis.
AB  - BACKGROUND: Cystic fibrosis related diabetes (CFRD) is associated with increased
      morbidity in CF. Variability in physiological systems is associated with
      dysfunctional homeostasis. We examined whether fluctuation in glucose is a marker
      of CFRD or "pre-diabetes". METHODS: Using a machine learning approach, we
      compared glucose IQR to current diagnostic criteria in a review of continuous
      glucose monitoring data. RESULTS: Analysis was performed on 248 studies from 142
      children. Calculated IQR (cIQR) was increased between children with CFRD, normal
      glucose homeostasis and indeterminate status (p<0.0001) and impaired glucose
      tolerance (p<0.05, Kruskal-Wallis test). In subjects who developed CFRD (n=20),
      cIQR increased between baseline and diagnosis (1.4mmol/L versus 2.4mmol/L,
      p<0.0001, Wilcoxon test). Area under the curve for CFRD on the basis of cIQR was
      0.865 (p<0.0001). Neither episodes of hypoglycaemia nor cIQR at baseline
      predicted CFRD. CONCLUSIONS: Glucose fluctuation on CGMS can be quantified by
      calculating the IQR. This information may improve early recognition of abnormal
      glucose homeostasis.

PMID- 29329722
TI  - Long-term Average Speech Spectra of Postlingual Cochlear Implant Users.

PMID- 29329720
TI  - Discoveries of Extrachromosomal Circles of DNA in Normal and Tumor Cells.
AB  - While the vast majority of cellular DNA in eukaryotes is contained in long linear
      strands in chromosomes, we have long recognized some exceptions like
      mitochondrial DNA, plasmids in yeasts, and double minutes (DMs) in cancer cells
      where the DNA is present in extrachromosomal circles. In addition, specialized
      extrachromosomal circles of DNA (eccDNA) have been noted to arise from repetitive
      genomic sequences like telomeric DNA or rDNA. Recently eccDNA arising from unique
      (nonrepetitive) DNA have been discovered in normal and malignant cells, raising
      interesting questions about their biogenesis, function and clinical utility.
      Here, we review recent results and future directions of inquiry on these new
      forms of eccDNA.

PMID- 29329723
TI  - Prolonged Grief and Cognitive Decline: A Prospective Population-Based Study in
      Middle-Aged and Older Persons.
AB  - OBJECTIVE: Bereavement can result in unresolved and prolonged grief, often termed
      prolonged grief disorder (PGD). The impact of PGD on cognitive functioning is
      poorly understood. The aim of the study was to compare the cognitive decline,
      assessed by repeated measures of different cognition domains, between persons
      with normal and PGD and a non-grieving reference population in a 7-year follow-up
      study. METHODS: The study sample comprised 3126 non-demented persons, mean age:
      64 years, of the Rotterdam Study. Participants were classified into three groups:
      no grief (reference group, N = 2,582), normal grief (N = 418), and prolonged
      grief disorder (N = 126). Participants were assessed with the Complicated Grief
      Inventory and underwent cognitive testing (Mini-Mental State Examination [MMSE],
      Letter-Digit Substitution test, Stroop test, Word fluency task, Word learning
      test). Analyses were adjusted for baseline cognition and depressive symptoms;
      persons with major depressive disorders were excluded. RESULTS: Compared with the
      reference group, participants with PGD showed a decrease in global cognitive
      function, MMSE scores, and World learning test (immediate and delayed) over time.
      Participants with normal grief did not show a stronger cognitive decline in any
      of cognitive tests than the reference group. CONCLUSIONS: Participants with PGD
      showed a stronger cognitive decline than the reference group during 7 years of
      follow-up. This suggests that PGD is a risk factor for cognitive decline, but
      this study cannot detect the psychobiological mechanism underlying this
      longitudinal association.

PMID- 29329724
TI  - The Potential of Cold Plasma for Safe and Sustainable Food Production.
AB  - Cold plasma science and technology is increasingly investigated for translation
      to a plethora of issues in the agriculture and food sectors. The diversity of the
      mechanisms of action of cold plasma, and the flexibility as a standalone
      technology or one that can integrate with other technologies, provide a rich
      resource for driving innovative solutions. The emerging understanding of the
      longer-term role of cold plasma reactive species and follow-on effects across a
      range of systems will suggest how cold plasma may be optimally applied to
      biological systems in the agricultural and food sectors. Here we present the
      current status, emerging issues, regulatory context, and opportunities of cold
      plasma with respect to the broad stages of primary and secondary food production.

PMID- 29329725
TI  - Aquagenic urticaria: Severe extra-cutaneous symptoms following cold water
      exposure.

PMID- 29329726
TI  - Patient-centered communication of community treatment assistants in Tanzania
      predicts coverage of future mass drug administration for trachoma.
AB  - OBJECTIVE: Prevention of Trachoma, the leading cause of infectious blindness,
      requires community treatment assistants (CTAs) to perform mass drug
      administration (MDA) of azithromycin. Previous research has shown that female
      CTAs have higher MDA coverage, but no studies have focused on the content of
      conversation. We hypothesize that female CTAs had more patient-centered
      communication and higher MDA coverage. METHODS: In 2011, CTAs from 23
      distribution sites undergoing MDA as part of the Partnership for Rapid
      Elimination of Trachoma were selected. CTA - villager interactions were audio
      recorded. Audio was analyzed using an adaptation of the Roter Interaction
      Analysis System. The outcome of interest was the proportion of adults receiving
      MDA in 2011 who returned in 2012. RESULTS: 58 CTAs and 3122 interactions were
      included. Sites with female CTAs had significantly higher patient-centeredness
      ratio (0.548 vs 0.400) when compared to sites with male CTAs. Sites with more
      patient-centered interactions had higher proportion of patients return (p =
      0.009). CONCLUSION: Female CTAs had higher proportion of patient-centered
      communication. Patient centered communication was associated with higher rates of
      return for MDA. PRACTICE IMPLICATIONS: Greater patient-centered connection with
      health care providers affects participation in public health efforts, even when
      those providers are lay health workers.

PMID- 29329727
TI  - Parent activation in the pediatric emergency department: Theory vs. reality.
AB  - OBJECTIVE: To measure parent activation and test for its associations with
      sociodemographics, clinical factors, and short-term outcomes. METHODS: By
      convenience sampling, 246 parents of children treated in an emergency department
      (ED) of a children's hospital completed the Parent-Patient Activation Measure (P
      PAM) and answered sociodemographic questions. Clinical information was abstracted
      from medical records. Phone calls to parents and primary care physician offices
      were conducted within one-month post-ED visit for information about short-term
      outcomes. RESULTS: We discovered higher than expected activation among our sample
      (mean = 73), higher activation scores by Spanish language and child chronic
      illness status, and associations between activation scores and ED visit and
      discharge instruction comprehension and filling prescriptions (short-term
      outcomes). However, the theory of parent activation did not adequately fit the
      data. CONCLUSION: Before the P-PAM in pediatric clinical care becomes widespread,
      further research is necessary to better understand parent activation and its
      associations with pediatric outcomes. PRACTICE IMPLICATIONS: Although the PAM has
      shown promise in accurately measuring patient activation across various
      populations and disease processes, the same is not yet true of the P-PAM. To
      date, pediatric studies using the P-PAM have called its psychometric properties
      into question. Further research is needed to understand and measure parent
      activation.

PMID- 29329728
TI  - Gene expression patterns associated with human placental trophoblast
      differentiation.
AB  - Cell fusion is a hallmark of placental trophoblast cell differentiation and the
      mature syncytiotrophoblasts play essential roles for fetal-maternal exchange and
      production of pregnancy-related hormones. Using a well-established in vitro
      trophoblast differentiation model, we performed a microarray analysis on mRNA
      expression in trophoblast and syncytiotrophoblast cell cultures. Dramatic changes
      in gene expression patterns were detected during trophoblast differentiation.
      Real-time PCR analysis confirmed the reliability of the microarray data. As many
      as 3524 novel and known genes have been found to be up- or down-regulated for >2
      fold. A number of cell cycle regulator including CDC6, CDC20, Cyclins B2, L1 and
      E2, were down-regulated in the syncytiotrophoblast, providing a mechanism for the
      loss of mitotic activity during trophoblast differentiation. Further
      characterization on the identified genes may lead to better understanding of
      placental patho-physiology in obstetric diseases such as preeclampsia.

PMID- 29329729
TI  - Elevated neuron-specific enolase and S100 calcium-binding protein B
      concentrations in cerebrospinal fluid of patients with anti-N-methyl-d-aspartate
      receptor encephalitis.
AB  - BACKGROUND: Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is a
      relatively common autoimmune neurological disease of the central nervous system
      (CNS). Neuron-specific enolase (NSE) and S100 calcium-binding protein B (S100B)
      are structural proteins of the central nervous system (CNS). In patients with CNS
      injury accompanied by nervous tissue and cellular damage, these structural
      proteins are released from cells; their extracellular concentrations, including
      those in cerebrospinal fluid (CSF) and blood, subsequently increase. METHODS:
      Thirty-six patients with anti-NMDAR encephalitis were prospectively recruited.
      The CSF NSE and S100B concentrations were measured in 19 and 17 patients,
      respectively. The CSF NSE and S100B concentrations were measured in 21 patients
      with noninflammatory neurological disease as controls. All measurements were
      performed using enzyme-linked immunosorbent assays. RESULTS: The CSF NSE and
      S100B concentrations were remarkably higher in the patients with anti-NMDAR
      encephalitis than in the controls. The early NSE or S100B concentrations in CSF
      were associated with the mRS. CONCLUSION: CSF NSE and S100B concentration in
      patients with anti-NMDAR encephalitis is higher than in patients with non
      inflammatory neurological disease. The early NSE or S100B concentrations in CSF
      were associated with the mRS and we can use it to determine the prognosis of the
      disease.

PMID- 29329730
TI  - Mechanical thrombectomy in acute ischaemic stroke: a review of the different
      techniques.
AB  - Endovascular mechanical thrombectomy (MT) is reserved for acute ischaemic stroke
      secondary to large vessel occlusion. The various MT techniques employed in the
      treatment of hyperacute strokes are constantly evolving with new devices and
      improvisation of existing technology (Wahlgren, et al 2016). In this review, we
      describe a variety of MT techniques gained from our experience of performing over
      350 procedures in 7 years of providing a 24/7 service within the national
      framework of a hyperacute stroke centre. We outline a number of endovascular
      techniques, procedure limitations, and potential complications.

PMID- 29329731
TI  - Multimodality imaging evaluation before transcatheter aortic valve implantation:
      incidence of contrast medium-induced acute kidney injury, risk factors and
      prognosis.
AB  - AIM: To evaluate the incidence, risk factors, and prognostic implications of
      contrast medium-induced acute kidney injury (CI-AKI) in patients undergoing
      transcatheter aortic valve implantation (TAVI) evaluation. MATERIALS AND METHODS:
      Datasets from 98 out of 207 consecutive patients referred for multidetector
      computed tomography (MDCT) for TAVI evaluation were eligible for evaluation and
      were analysed retrospectively. The incidence of CI-AKI was correlated to outcome
      and to potential risk factors: kidney function (estimated glomerular filtration
      rate [eGFR]), heart failure, diabetes, amount of contrast medium, and duration of
      examination period. RESULTS: CI-AKI occurred in 67 patients (68.4%) and mainly
      correlated with eGFR (p=0.01) and the amount of contrast medium as a function of
      eGFR (p=0.04). CI-AKI occurred before TAVI in 36 (53.7%) patients of which 13
      (19.4%) did not undergo TAVI. In-hospital all-cause mortality was 21.4%, and of
      those 21 patients, 18 (85.7%) had CI-AKI and nine (42.9%) did not undergo TAVI.
      One-year all-cause mortality was 39.8%, and of those 39 patients who died within
      1 year, 31 (79.5%) had CI-AKI. CONCLUSION: CI-AKI mostly occurs already before
      TAVI as a consequence of pre-procedural imaging, which therefore represents the
      main contributor for CI-AKI in relation to TAVI. Regarding the observation that
      some patients will ultimately have no benefit because TAVI is not performed and
      the poor prognosis linked to CI-AKI should encourage improvement in patient
      selection when referring to pre-procedural imaging.

PMID- 29329732
TI  - Changes in quantitative CT image features of ground-glass nodules in
      differentiating invasive pulmonary adenocarcinoma from benign and in situ
      lesions: histopathological comparisons.
AB  - AIM: To evaluate progressive changes in quantitative CT features of the non-solid
      component of ground-glass nodules (GGNs) from baseline to follow-up to
      differentiate invasive (minimally invasive adenocarcinoma [MIA] and invasive
      adenocarcinoma [IA]) GGNs from benign or pre-invasive (adenocarcinoma in situ
      [AIS]) lesions. MATERIALS AND METHODS: Patients with a GGN detected at baseline
      and follow-up computed tomography (CT), examined by tissue sampling were included
      in the study. The diameter and mean, maximum, minimum CT density and density
      deviation from the non-solid component of whole GGNs were measured. Progression
      of these features over time was analysed by linear regression analysis.
      Multivariate receiver operating characteristics analyses of combined measures
      created by a logistic regression model were performed to evaluate diagnostic
      performance for invasive GGNs. RESULTS: Sixty-one patients (24 males) with 70
      GGNs were included. Fifteen GGNs were benign, six AIS, 38 MIA, and 11 IA. The
      mean diameter of all histological subtypes increased from baseline to follow-up,
      the largest increase was found in the MIA group (p<0.001). For MIA and IA, the
      mean, maximum, minimum density, and density deviation had a positive correlation
      over time, whilst benign and pre-invasive GGNs showed a negative correlation for
      these features. A diagnostic model based on three GGN features (increasing in
      diameter, mean density, and density deviation) identified invasive GGNs with a
      sensitivity, specificity and area under the receiver operating characteristic
      (ROC) curve (AUC) of 83.7%, 61.9%, and 0.786, respectively (p<0.001). CONCLUSION:
      In GGN follow-up, the diameter of benign and AIS, and invasive GGNs significantly
      increased. Additional analysis of mean density and density deviation in the non
      solid component may help to identify invasive GGNs.

PMID- 29329733
TI  - Association between leukoaraiosis and cerebral blood flow territory alteration in
      asymptomatic internal carotid artery stenosis.
AB  - AIM: To test the hypothesis that leukoaraiosis (also known as white matter
      lesion) is associated with cerebral blood flow territory change as revealed by
      territorial arterial spin-labeling (TASL) magnetic resonance imaging (MRI) in
      patients with asymptomatic internal carotid artery stenosis (aICAS). MATERIALS
      AND METHODS: The institutional review board approved this study. Thirty-three
      patients with aICAS were included prospectively and divided into high-grade
      (ultrasonographic stenosis >=70%, n=17) and low-grade (n=16) groups; 16 healthy
      subjects were also included. Cerebral flow territory was delineated for left ICA,
      right ICA, and vertebral arteries using TASL MRI and fuzzy clustering. Two
      licensed neuroradiologists independently and dichotomously rated the
      hemispherical asymmetry of flow territories. Flow territories were finalised by
      consensus, and when asymmetry was present, these were divided into normal and
      abnormal areas where the raters separately assessed leukoaraiosis based on fluid
      attenuated inversion recovery images and the Fazekas scale. RESULTS: The inter
      rater agreement in the evaluation of flow territory asymmetry with TASL imaging
      in conjunction with time-of-flight angiogram is substantial (Cohen's kappa=0.82).
      Multinomial logistic regression (reference group=healthy subjects) indicates that
      global leukoaraiosis is not a predictor of aICAS after controlling for age,
      whereas in high-grade patients, the deep white matter lesion is more severe in
      the area receiving collateral circulation than in the area with normal flow
      territory (Wilcoxon signed-rank test, p=0.03). CONCLUSION: TASL MRI is clinically
      feasible in aICAS and shows that more severe deep white matter lesions are
      associated with collateral circulation in high-grade patients.

PMID- 29329734
TI  - The morphological changes of bronchovascular bundles within subsolid nodules on
      HRCT correlate with the new IASLC classification of adenocarcinoma.
AB  - AIM: To observe the morphological changes of bronchovascular bundles within
      subsolid nodules on high-resolution (HR) computed tomography (CT) and analyse the
      correlation with the new adenocarcinoma classification. MATERIALS AND METHODS:
      Two hundred and sixteen lesions (absent consolidation on mediastinal window) were
      reviewed retrospectively. CT features including dimensions, contour,
      morphological changes of the blood vessels, and bronchi/bronchioles, vacuole
      signs, and their correlation with histopathology were evaluated. RESULTS:
      Excluding nine non-cancerous lesions, 34 pre-invasive lesions (PILs) including 15
      atypical adenomatous hyperplasias (AAHs) and 19 adenocarcinomas in situ (AISs),
      21 minimally invasive adenocarcinomas (MIAs), and 152 invasive adenocarcinomas
      (IACs) were analysed. Lepidic, acinar, and papillary patterns were identified in
      this cohort of adenocarcinomas. IACs were grouped into three types: type I
      (lepidic pattern >=80%, n=47), type II (lepidic pattern >=50%, <80%, n=67), and
      type III (lepidic pattern <50%, n=38). The contour of lesions, and morphological
      changes in vessels and bronchi/bronchioles significantly correlated with the
      classification of PIL, MIA, and IACs (p=0.000, p=0.000, and p=0.017,
      respectively). In IACs, the prevalence of vascular abnormalities on HRCT
      significantly correlated with (p=0.000) the proportion of non-lepidic pattern
      (23.40% in type I, 58.21% in type II, and 76.32% in type III); the prevalence of
      bronchial/bronchiolar abnormalities was higher (p=0.008) in type II/III (20.95%)
      compared with type I (6.38%). CONCLUSIONS: The morphological changes of vessels
      and bronchi/bronchioles within the subsolid nodules on HRCT help to differentiate
      IAC from PIL and MIA, and are more common in non-lepidic predominant
      adenocarcinomas.

PMID- 29329736
TI  - Research on Adolescent Sexuality Should Be Inclusive of Disability.

PMID- 29329737
TI  - The Authors reply.

PMID- 29329735
TI  - Diagnostic value of early postoperative MRI and diffusion-weighted imaging
      following trans-sphenoidal resection of non-functioning pituitary macroadenomas.
AB  - AIM: To establish the value of early contrast-enhanced magnetic resonance imaging
      (MRI) and diffusion-weighted imaging (DWI) in differentiating residual pituitary
      adenoma from postoperative surgical changes. MATERIALS AND METHODS: Thirty
      patients with non-functioning pituitary macroadenomas, who were undergoing trans
      sphenoidal adenomectomy, were prospectively studied. Patients were imaged with
      both MRI and DWI in the early postoperative period, as well as 6-months post
      surgery. Patterns of postoperative contrast enhancement were described (non
      enhancement, peripheral enhancement, and nodular enhancement). Apparent diffusion
      coefficient (ADC) maps were utilised to select the region of interest (ROI) for
      ADC calculations. RESULTS: Seventeen patients had postoperative surgical
      granulation tissue and 13 had residual adenoma based on the 6 months follow-up
      imaging. Mean ADC values of postoperative granulation tissue and residual adenoma
      were 1.476+/-0.476*10-3 mm2/s and 0.855+/-0.190*10-3 mm2/s, respectively, in the
      early postoperative period, and 1.357+/-0.416*10-3 mm2/s and 0.829+/-0.201*10-3
      mm2/s, respectively, at the 6-month follow-up. ADC values of granulation tissue
      were significantly different from that of residual adenoma at both time points
      (p<0.001). Sensitivity, specificity, positive and negative predictive values of
      early MRI were 84.6%, 94.1%, 91.7%, and 88.9% respectively, and of early DWI were
      91%, 97%, 94.3%, and 93%, respectively. CONCLUSION: Early postoperative DWI after
      trans-sphenoidal resection of pituitary macroadenomas may be more helpful than
      early MRI in differentiating residual adenoma from post-surgical changes.

PMID- 29329738
TI  - Relationship Between Proprioception and Endurance Functionality of the Cervical
      Flexor Muscles in Chronic Neck Pain and Asymptomatic Participants.
AB  - OBJECTIVE: The purpose of this study was to compare the relationship between
      flexion endurance capacity and joint position error in participants with or
      without chronic neck pain (CNP). METHODS: Sixty-one CNP and 60 asymptomatic
      volunteers participated in this cross-sectional, case-control, and correlational
      analysis study. The measured variables included absolute and constant joint
      repositioning errors in the sagittal and horizontal directions, clinical flexor
      endurance test score, pain intensity, and neck disability index. RESULTS: The
      groups did not statistically differ in flexion endurance (P > .05). The CNP group
      had a smaller absolute error on the right (P < .01) and left (P = .01) rotation
      and an overshooting error pattern in the flexion direction (P < .05). But the
      asymptomatic group did not exhibit any over-/undershooting pattern tendency (P >
      .05). Although flexion endurance was not correlated with any of the joint
      repositioning error components in either group, pain and disability scores were
      significantly correlated with left rotation absolute error (r = -0.34 and rho = 
      0.37, respectively). CONCLUSION: The clinical cervical flexor endurance test,
      ignoring the relative contribution of the deep and superficial groups of muscles,
      may not efficiently characterize CNP patients.

PMID- 29329739
TI  - Association Between Symptoms of Central Sensitization and Cognitive Behavioral
      Factors in People With Chronic Nonspecific Low Back Pain: A Cross-sectional
      Study.
AB  - OBJECTIVE: The objective of this cross-sectional study was to analyze the
      relationship between symptoms of central sensitization (CS) and important
      cognitive behavioral and psychosocial factors in a sample of patients with
      chronic nonspecific low back pain. METHODS: Participants with chronic nonspecific
      low back pain for at least 3 months were included in the study. They completed
      several questionnaires and a functional test. Pearson's correlation was used to
      analyze associations between symptoms of CS and pain behavior, functioning, pain,
      pain catastrophizing, kinesiophobia, and illness perceptions. Additionally, a
      between-group analysis was performed to compare patients with and without
      clinically relevant symptoms of CS. RESULTS: Data from 38 participants were
      analyzed. Significant associations were found between symptoms of CS and all
      other outcomes, especially current pain (r = 0.510, P = .001), mean pain during
      the past 7 days (r = 0.505, P = .001), and pain catastrophizing (r = 0.518, P =
      .001). Patients with clinically relevant symptoms of CS scored significantly
      worse on all outcomes compared with persons without relevant symptoms of CS,
      except on functioning (P = .128). CONCLUSIONS: Symptoms of CS were significantly
      associated with psychosocial and cognitive behavioral factors. Patients
      exhibiting a clinically relevant degree of symptoms of CS scored significantly
      worse on most outcomes, compared with the subgroup of the sample with fewer
      symptoms of CS.

PMID- 29329740
TI  - Criteria to Screen for Traumatic Cervical Spine Instability: A Consensus of
      Chiropractic Radiologists.
AB  - OBJECTIVE: The purpose of this study was to establish consensus on a radiographic
      definition for cervical instability for routine use in chiropractic patients who
      sustain trauma to the cervical spine. METHOD: We conducted a modified Delphi
      study with a panel of chiropractic radiologists. Panelists were asked to rate
      potential screening criteria for traumatic cervical spine instability when
      assessing cervical spine radiographs. Items rated as important for inclusion by
      at least 60% of participants in round 1 were submitted for a second round of
      voting in round 2. Items rated for inclusion by at least 75% of the participants
      in round 2 were used to create the consensus-based list of screening criteria.
      Participants were asked to vote and reach agreement on the final screening
      criteria list in round 3. RESULTS: Twenty-nine chiropractic radiologists
      participated in round 1. After 3 rounds of survey, 85% of participants approved
      the final consensus-based list of criteria for traumatic cervical spine
      instability screening, including 6 clinical signs and symptoms and 5 radiographic
      criteria. Participants agreed that the presence of 1 or more of these clinical
      signs and symptoms and/or 1 or more of the 5 radiographic criteria on routine
      static radiographic studies suggests cervical instability. CONCLUSION: The
      consensus-based radiographic definition of traumatic cervical spine instability
      includes 6 clinical signs and symptoms and 5 radiographic criteria that doctors
      of chiropractic should apply to their patients who sustain trauma to the cervical
      spine.

PMID- 29329741
TI  - Sex differences of hippocampal structure in bipolar disorder.
AB  - Although differential patterns in clinical characteristics have been consistently
      noted between male and female patients with bipolar disorder (BD), the effect of
      sex on the hippocampal structure remains unclear. To address this, the present
      study investigated the effects of BD and sex on the hippocampal structure, and
      the relationship between the hippocampal structure and cognitive performance.
      Morphometric and neurocognitive analyses were performed in 91 subjects (patients
      with BD: male/female = 33/19; normal controls: male/female = 22/17). Patients had
      significantly decreased left parahippocampal gyrus area and left/right
      hippocampal volume compared to normal controls. Within the BD group only, female
      patients presented with smaller right hippocampal volume than males. In the
      Spatial Span (SS) test (used to assess working memory capacity) and the Maze test
      (used to evaluate the ability to anticipate), patients demonstrated decreased
      performance compared to normal controls, with a significant main effect of sex.
      Left parahippocampal gyrus area and right hippocampal volume were positively
      correlated with SS and Maze in patients; moreover, right hippocampal volume
      predicted 17.4% of SS performance variance. These results suggest that there may
      be a difference between male and female patients with regard to right hippocampal
      volume, and that female patients may need more attention than males.

PMID- 29329742
TI  - Frontal activity measured by near-infrared spectroscopy in patients taking
      different atypical antipsychotic drugs: A cross-sectional study.
AB  - Using near-infrared spectroscopy, we examined changes in the concentration of
      oxygenated hemoglobin ([oxy-Hb]) in the frontal lobe during a verbal fluency task
      in 20 patients with schizophrenia (10 patients each receiving olanzapine [OLZ]
      and risperidone [RIS]) and 10 healthy controls. We found that [oxy-Hb] levels in
      the prefrontal region were higher in the patients receiving OLZ than in those
      receiving RIS. These results suggest that antipsychotic drugs have different
      effects on cerebral hemodynamic patterns, which may reflect frontal lobe
      function. Further studies with a larger sample size are needed to verify our
      preliminary findings.

PMID- 29329744
TI  - Letter to the Editor regarding "Use of both anterograde and retrograde internal
      mammary vessels in the bipedicled deep inferior epigastric perforator flap for
      unilateral breast reconstruction".

PMID- 29329743
TI  - GABA and glutamate in children with Tourette syndrome: A 1H MR spectroscopy study
      at 7T.
AB  - Tourette syndrome (TS) is characterized by presence of chronic, fluctuating motor
      and phonic tics. The underlying neurobiological basis for these movements is
      hypothesized to involve cortical-striatal-thalamo-cortical (CSTC) pathways. Two
      major neurotransmitters within these circuits are gamma-aminobutyric acid (GABA)
      and glutamate. Seventy-five participants (32 with TS, 43 controls) ages 5-12
      years completed 1H MRS at 7T. GABA and glutamate were measured in dorsolateral
      prefrontal cortex (DLPFC), ventromedial prefrontal cortex (VMPFC), premotor
      cortex (PMC), and striatum, and metabolites quantified using LCModel.
      Participants also completed neuropsychological assessment emphasizing inhibitory
      control. Scans were well tolerated by participants. Across ROIs combined,
      glutamate was significantly higher in the TS group, compared to controls, with no
      significant group differences in GABA observed. ROI analyses revealed
      significantly increased PMC glutamate in the TS group. Among children with TS,
      increased PMC glutamate was associated with improved selective motor inhibition;
      however, no significant associations were identified between levels of glutamate
      or GABA and tic severity. The dopaminergic system has long been considered to
      have a dominant role in TS. Accumulating evidence, however, suggests involvement
      of other neurotransmitter systems. Data obtained using 1H MRS at 7T supports
      alteration of glutamate within habitual behavior-related CSTC pathways of
      children with TS.

PMID- 29329745
TI  - Poly(methyl methacrylate) salt as film forming material to design orodispersible
      films.
AB  - This work aims to evaluate the possible use of a poly(sodium methacrylate, methyl
      methacrylate) (NaPMM2) plasticized by PEG400 in the design of orodispersible
      films (ODF). Placebo ODF prepared by solvent casting were intended to study the
      impact of the polymer/plasticizer ratio and residual moisture on disintegration
      time, stickiness and mechanical properties. The drug loading capacity was
      assessed using ketoprofen and paracetamol. Placebo ODF containing PEG400 in the
      10-30% w/w range and 10-15% of residual moisture content were easy-to-handle,
      packed without failures and completely dissolved within 30 s. NaPMM2/PEG400 in
      80/20 ratio allowed up to 70% of paracetamol loading, which appeared as the
      largest value described in literature. This ODF showed good mechanical properties
      and disintegration time. The same formulation loaded with 25% or 50% ketoprofen
      (pKa = 4.45) swelled without disintegrating, because of a partial protonation of
      NaPMM2, as verified by ATR-FTIR spectroscopy. However, the addition of 5%
      surfactants allowed the formulation of ODF containing 25% ketoprofen that
      disintegrated within one minute and guaranteed the complete drug dissolution
      within 5 min. All the presented data, discussed in the framework of information
      available on such copolymer, highlighted its versatility in the design of
      orodispersible dosage forms.

PMID- 29329746
TI  - Evaluation of a transtympanic delivery system in Mus musculus for extended
      release steroids.
AB  - OBJECTIVE: The current investigation evaluated a novel extended release delivery
      system for treating inner ear diseases. The platform technology consists of a
      film forming agent (FFA) and microsphere component to localize and extend drug
      delivery within the ear. STUDY DESIGN: Studies evaluated dissolution kinetics of
      microspheres with multiple encapsulates, testing of a variety of FFAs, and
      ability to localize to the round window membrane in mice in vivo. SETTING:
      Studies were completed at Orbis Biosciences and The University of Kansas Medical
      Center. SUBJECTS: In conjunction with in vitro characterization, an infrared dye
      containing microsphere formulation was evaluated for round window membrane (RWM)
      localization and general tolerability in C57/BL6 Mus musculus for 35 days.
      METHODS: In vitro characterization was performed using upright diffusion cells on
      cellulose acetate membranes, with drug content quantified by high performance
      liquid chromatography. Mus musculus dosing of infrared dye-containing
      microspheres was performed under anesthesia with a 27 GA needle and 2.0 MUL
      injection volume RESULTS: In vitro dissolution demonstrates the ability of the
      FFA with microsphere platform to release steroids, proteins, peptides, and
      nucleic acids for at least one month, while necroscopy shows the ability of the
      FFA with dye-loaded microspheres to remain localized to Mus musculus RWM for the
      same period of time, with favorable tolerability. CONCLUSIONS: Combining FFA and
      microsphere for localized drug delivery may enable cost-effective, extended
      release local delivery to the inner ear of new and existing small molecules,
      proteins, peptides, and nucleic acids.

PMID- 29329747
TI  - Antibacterial properties of Latarcin 1 derived cell-penetrating peptides.
AB  - Cell-penetrating peptides (CPPs) and antimicrobial peptides (AMPs) share certain
      physicochemical parameters such as amphipathicity, hydrophobicity, cationicity
      and pI, due to which these two groups of peptides also exhibit overlapping
      functional characteristics. In our current work, we have evaluated antimicrobial
      properties of cell-penetrating peptides derived from Latarcin1. Latarcin derived
      peptide (LDP) exhibited antimicrobial activity against representative
      microorganisms tested and bactericidal effect against methicillin resistant
      Staphylococcus aureus (MRSA), which was used as model organism of study in the
      present work. However, LDP exhibited cytotoxicity against HeLa cells. Further,
      nuclear localization sequence (NLS) was fused to LDP and interestingly, LDP-NLS
      showed antimicrobial effect against bacteria, showed bactericidal effect against
      MRSA and also did not exhibit cytotoxicity in HeLa cells till the highest
      concentrations tested. Thus, our results inferred that fusion of NLS to LDP
      significantly reduced cytotoxicity of LDP against HeLa cells (Ponnappan and
      Chugh, 2017) and exhibited significantly higher cell-penetrating activity in MRSA
      in comparison to LDP alone. Consolidated results of uptake assays, time-kill
      assays and PI membrane damage assays show that LDP killed MRSA mainly by membrane
      damage, where as LDP-NLS might have intracellular targets. Owing to its cell
      penetrating activity in HeLa cells and antimicrobial activity against MRSA, LDP
      NLS efficiently inhibited intracellular infection of MRSA in HeLa cells as
      observed in invasion assays. Hence, our results suggest that LDP-NLS is a dual
      action peptide with AMP and CPP activity and could be potential candidate as
      peptide antibiotic and drug delivery vector in both mammalian and bacterial
      cells.

PMID- 29329748
TI  - Oral Bifidobacterium longum expressing GLP-2 improves nutrient assimilation and
      nutritional homeostasis in mice.
AB  - Bifidobacterium has been developed for the oral delivery of peptides and has the
      added beneficial effect on our bodies through its probiotic properties. Here, we
      utilize Bifidobacterium as a delivery system to orally deliver Glucagon like
      peptide-2 (GLP-2). We constructed vector derived from pET-31b(+) to construct a
      Bifidobacterium longum expressing GLP-2. We then determined the bioactivity of
      recombinant Bifidobacterium in Caco-2 cells. Finally, we quantified newly
      synthesized ApoB48 and chylomicron production in mice infused with exogenous GLP
      2 or Bifidobacterium expressing GLP-2. Results based on secretion of the
      triglyceride (TG)-rich lipoprotein (TRL)-ApoB48 and secretion of chylomicron
      revealed that recombinant Bifidobacterium was efficient in treating intestinal
      dysfunction,suggesting an alternative way to use Bifidobacterium as a delivery
      system to deliver GLP-2 for gastrointestinal nutrition coordination.

PMID- 29329749
TI  - Assessment of the diagnostic performance of four methods for the detection of
      Giardia duodenalis in fecal samples from human, canine and feline carriers.
AB  - Enteric parasitic diseases including giardiasis are of public health concern.
      Different methods are available for the diagnosis of this parasitic infection in
      fecal samples such as the identification of protozoan cysts and trophozoites by
      light microscopy, detection of specific antigens by ELISA, and amplification of
      DNA fragments by PCR. The present study aimed at assessing the performance of
      four laboratory tests for the detection of Giardia duodenalis in fecal specimens
      from three different host species with a previous diagnosis of giardiasis;
      canine, feline and human patients provided new stool samples to be retested for
      Giardia before initiating treatment with antiprotozoal drugs. For this purpose,
      triplicate fecal specimens from 54 humans, 24 dogs and 18 cats living in the city
      of Niteroi, RJ, southeast Brazil, were analysed by light microscopy, ELISA,
      immunochromatography, and nested PCR. The centrifugal-flotation method detected
      Giardia cysts in 89.6% (86/96) of the fecal samples. The protozoan parasite was
      detected via immunochromatography in 87.5% (84/96) of these samples. Giardia was
      detected by ELISA in 69.8% (67/96) of the stool specimens from carriers with a
      previous diagnosis of Giardia infection. Giardia was detected by PCR in only
      39.6% (38/96) of the fecal specimens. Based on these findings, we suggest that,
      among the four assays that were used in this study, the zinc sulphate flotation
      technique (Faust et al., 1939) is the best diagnostic assay in terms of
      sensitivity and specificity to detect G. duodenalis on serially collected samples
      from dogs, cats and humans.

PMID- 29329750
TI  - Women and the Experience of Pain and Opioid Use Disorder: A Literature-based
      Commentary.
AB  - It is generally understood that pain experience and opioid abuse have relied on
      male-dominated models. However, sex and gender play a role in both pain
      experience and opioid use disorder. Using the previously validated Texas Tech
      University Health Sciences Center Sex and Gender Specific Health PubMed Advanced
      Search Tool, the authors used pertinent literature to develop this literature
      based commentary on sex and gender differences in pain experience and opioid use
      disorder. Women report their experience of pain more frequently, have increased
      rates of diagnoses related to pain, have increased pain sensitivity, and have a
      variable response to pain and analgesia. This variable response is due to
      anatomic, physiologic, hormonal, psychological, and social factors that differ by
      sex and gender. Women have been found to be at greater risk for opioid abuse in
      all age groups. This may be due to the differences in pain experience, as well as
      sex and gender differences in prescribing patterns, cultural norms, and the
      increased likelihood to experience dependency and withdrawal. Approaches to the
      treatment of opioid use disorder are also subject to sex and gender differences
      an area in need of further investigation.

PMID- 29329751
TI  - Progress in the neurosciences and the training of medical students.

PMID- 29329752
TI  - Role of frozen section in sentinel lymph node biopsy for breast cancer in the era
      of the ACOSOG Z0011 and IBCSG 23-10 trials.
AB  - BACKGROUND: Intraoperative frozen sections (FS) of sentinel lymph nodes (SLN)
      were evaluated to avoid the need for deferred axillary lymph node dissection
      (ALND) in patients with early breast cancer (EBC). However, FS has low
      sensitivity for detecting micro-metastases (<2 mm), resulting in patients who
      later undergo deferred ALND. The aim of the study was to determine the best
      clinical approach for selecting patients who would derive real benefit from ALND,
      as well as to minimize the functional and psychological damage caused by delayed
      surgery, and the risk of undertreating EBC patients. METHODS: This study
      evaluated 1453 patients with early breast cancer (EBC) who underwent SLN biopsy,
      FS and definitive evaluation. Causes of discrepancies between SLN biopsy and FS
      results and the need for further surgery were evaluated. RESULTS: A total of 1226
      (86%) patients underwent FS; of these patients, 146 (11.9%) were false negatives.
      The global sensitivity of FS in detecting both macro and micrometastases was
      53.7%. Although ACOSOG Z0011 criteria found that ALND could be avoided in 236
      patients, 40 (17%) of these had >3 positive axillary lymph nodes. In contrast,
      application of the IBCSG 23-10 trial criteria, found that only three patients
      (3.1%) had >3 positive axillary lymph nodes. CONCLUSIONS: FS has a low
      sensitivity in detecting micrometastases (19%), but a reasonable sensitivity for
      macrometastases (75%). Most false negatives were smaller metastases (mean 2.1 mm)
      and more likely in patients with infiltrating lobular carcinoma. Retrospective
      modelling of the IBCSG 23-10 criteria reduced the percentage of patients
      requiring deferred surgery from 12% to 4%. Guidelines recommend irradiation of
      lymph node drainage stations in patients with >=4 axillary metastatic lymph
      nodes. Omission of ALND from 40% of patients who met Z0011 criteria would have
      resulted in their undertreatment. This risk decreases to 3% by omitting axillary
      clearing only in patients with micrometastases.

PMID- 29329753
TI  - Does social context matter? An ecological momentary assessment study of marijuana
      use among college students.
AB  - INTRODUCTION: Past research has shown that marijuana use occurs commonly in
      social situations for young adults, though few studies have examined the
      association between immediate social context and marijuana use patterns and
      associated problems. The current study examined the impact of demographics,
      marijuana use and problem use, alcohol use, craving, and social context on the
      likelihood of using marijuana with others via ecological momentary assessment
      (EMA). METHODS: College-student marijuana users (N=56) were recruited and
      completed a baseline assessment and training on the two-week signal-contingent
      EMA protocol. Participants were sent text messages three times per day randomly
      for two weeks. RESULTS: Of the 1131 EMA instances during which participants
      reported using marijuana, 862 (76.22%) were labeled as being with others. Forty
      five participants (80.36%) reported marijuana use with others present during at
      least half of the times they used marijuana. Findings from a multilevel logistic
      regression model showed a significant positive association between the
      probability of using with others and minutes spent using marijuana (b=0.047,
      p<0.001), social facilitation (b=0.138, p<0.001), and DSM-IV diagnosis
      (dependence versus no diagnosis, b=1.350, p=0.047). CONCLUSIONS: Cannabis
      dependence, more time using marijuana in the moment, and using for social
      facilitation purposes were positively associated with using marijuana in the
      context of being with others. Daily users had more variability in terms of the
      social context of their use. This study illustrates the complex relationship
      between social context and marijuana use.

PMID- 29329754
TI  - Comparison of Cepheid(r) Xpert Flu and Roche RealTime Ready Influenza A/H1N1
      Detection Set for detection of influenza A/H1N1.
AB  - OBJECTIVE: To compare two influenza polymerase chain reaction (PCR) methods.
      METHODS: A total of 749 suspected MERS-CoV patients presenting at Johns Hopkins
      Aramco Healthcare, Saudi Arabia, each submitted a clinical sample for influenza A
      reflex testing using the on-site Cepheid(r) Xpert Flu assay and at the Ministry
      of Health laboratory by the Roche PCR assay. RESULTS: There was 92.12% overall
      agreement between the two methods. Specificity of the Cepheid(r) Xpert Flu was
      95.8% for H1N1 and 94.4% for total influenza A. Cepheid(r) Xpert Flu sensitivity
      for influenza A was 100% for younger patients (0-19-year age group) but
      significantly lower both for older patients (68.2% for 60-79-year and 50% for
      >=80-year age groups) and overall for males compared to females (72.6% and 94.0%,
      respectively). CONCLUSIONS: Specificity of the Cepheid(r) Xpert Flu test was
      high; however, sensitivity for total influenza A was lower particularly in males
      and older patients.

PMID- 29329755
TI  - Detection of "Xisco" gene for identification of Streptococcus pneumoniae
      isolates.
AB  - We describe a PCR-assay differentiating Streptococcus pneumoniae from closely
      related species of the Mitis group of the genus Streptococcus and identification
      of pneumococcus clinical isolates, based on the "Xisco" gene discriminatory
      marker. The complete "Xisco" gene sequence was observed in all S. pneumoniae
      genomes analyzed and absent in all non-pneumococcus genomes.

PMID- 29329756
TI  - Phospholipid composition of the outer membrane of Escherichia coli influences its
      susceptibility against antimicrobial peptide apidaecin 1b.
AB  - Proline-rich antimicrobial peptides (PrAMPs) kill bacteria in a multimodal
      mechanism by inhibiting the 70S ribosome (i.e., protein translation) as dominant
      lethal mechanism besides inhibition of several other proteins, such as chaperone
      DnaK. PrAMPs pass the outer membrane of Gram-negative bacteria, probably by a
      self-promoted uptake followed by a transporter-mediated uptake from the
      periplasm. Mutation of transporter protein SbmA is a well-studied resistance
      mechanism observed in vitro by resistance induction with PrAMPs. Here, we
      compared the membrane compositions of Escherichia coli BL21AI and BL21AI Apir,
      which was obtained by resistance induction with PrAMP apidaecin 1b. Lipid A was
      partially modified by phosphatidylethanolamine, 4-aminoarabinose, or both groups,
      but the relative contents of these and further unidentified species did not
      differ much between wild-type and resistant strains, indicating that resistance
      was not related to lipid A modifications. The same was true for 20
      glycerophospholipids identified, i.e., 11 phosphatidylethanolamines and 9
      phosphatidylglycerols. However, glycerophospholipids in BL21AI Apir contained
      much lower levels of cyclopropane-modified acyl groups, which probably alter the
      biophysical properties of the inner membrane and the inner leaflet of the outer
      membrane. Indeed, when cyclopropane-fatty-acyl-phospholipid synthase was knocked
      out in E. coli BW25113, the resulting BW25113 Deltacfa was less susceptible
      against apidaecin 1b.

PMID- 29329758
TI  - Real-time RT-PCR, a necessary tool to support the diagnosis and surveillance of
      rotavirus in Mexico.
AB  - Rotavirus produces diarrhea in children under 5 years old. Most of those
      conventional methods such as polyacrylamide gel electrophoresis (PAGE) and
      reverse transcription-polymerase chain reaction (RT-PCR) have been used for
      rotavirus detection. However, these techniques need a multi-step process to get
      the results. In comparison with conventional methods, the real-time RT-PCR is a
      highly sensitive method, which allows getting the results in only one day. In
      this study a real-time RT-PCR assay was tested using a panel of 440 samples from
      patients with acute gastroenteritis, and characterized by PAGE and RT-PCR. The
      results show that the real-time RT-PCR detected rotavirus from 73% of rotavirus
      negative samples analyzed by PAGE and RT-PCR; thus, the percentage of rotavirus
      positive samples increased to 81%. The results indicate that this real-time RT
      PCR should be part of a routine analysis, and as a support of the diagnosis of
      rotavirus in Mexico.

PMID- 29329759
TI  - Treatment outcomes of macrolide-susceptible Mycobacterium abscessus lung disease.
AB  - Mycobacterium abscessus lung disease is difficult to treat due to inducible
      resistance to macrolides. However, 15%-20% of isolates are macrolide susceptible.
      In 14 patients with macrolide-susceptible M. abscessus lung disease, all isolates
      had nonfunctional erm(41) gene, and sputum culture conversion rate was achieved
      in 93% (13/14) following antibiotic therapy.

PMID- 29329757
TI  - Challenges of Francisella classification exemplified by an atypical clinical
      isolate.
AB  - The accumulation of sequenced Francisella strains has made it increasingly
      apparent that the 16S rRNA gene alone is not enough to stratify the Francisella
      genus into precise and clinically useful classifications. Continued whole-genome
      sequencing of isolates will provide a larger base of knowledge for targeted
      approaches with broad applicability. Additionally, examination of genomic
      information on a case-by-case basis will help resolve outstanding questions
      regarding strain stratification. We report the complete genome sequence of a
      clinical isolate, designated here as F. novicida-like strain TCH2015, acquired
      from the lymph node of a 6-year-old male. Two features were atypical for F.
      novicida: exhibition of functional oxidase activity and additional gene content,
      including proposed virulence determinants. These differences, which could
      potentially impact virulence and clinical diagnosis, emphasize the need for more
      comprehensive methods to profile Francisella isolates. This study highlights the
      value of whole-genome sequencing, which will lead to a more robust database of
      environmental and clinical genomes and inform strategies to improve detection and
      classification of Francisella strains.

PMID- 29329760
TI  - Sodium-glucose transporter as a novel therapeutic target in disease.
AB  - Glucose is the primary energy fuel of life. A glucose transporter, the sodium
      glucose transporter (SGLT), is receiving attention as a novel therapeutic target
      in disease. This review summarizes the physiological role of SGLT in cerebral
      ischemia, cancer, cardiac disease, and intestinal ischemia, which has encouraged
      analysis of SGLT function. In cerebral ischemia and cardiomyopathy, SGLT-1 is
      involved in worsening of the injury. In addition, SGLT-1 promotes the development
      of cancer. On the other hand, SGLT-1 has a protective effect against cardiac and
      intestinal ischemia. Interestingly, SGLT-1 expression levels are increased in
      some diseased tissue, such as in cerebral ischemia and cancer. This suggests that
      SGLT-1 may have an important role in many diseases. This review discusses the
      potential of SGLT as a target for novel therapeutic agents.

PMID- 29329761
TI  - N-terminal pro-B-type natriuretic peptide for monitoring after balloon pulmonary
      angioplasty for chronic thromboembolic pulmonary hypertension.
AB  - BACKGROUND: Balloon pulmonary angioplasty (BPA) is an emerging interventional
      treatment option for chronic thromboembolic pulmonary hypertension (CTEPH). The
      non-invasive monitoring of CTEPH patients is a clinical challenge. In this study
      we examined changes in N-terminal pro-B-type natriuretic peptide (NT-proBNP) in
      patients undergoing BPA for inoperable CTEPH and related them to peri-procedural
      success. METHODS: In this study we analyzed a total of 51 consecutive patients
      who underwent BPA treatment and completed a 6-month follow-up (6-MFU) between
      March 2014 and March 2017. Serum samples for NT-proBNP measurement were collected
      before every BPA and at 6-MFU. RESULTS: The 51 patients underwent 265
      interventions involving angioplasty of a total of 410 vessels. The 6-month
      survival rate was 96.1%. The baseline (BL) mean pulmonary artery pressure (PAP)
      was 39.5 +/- 12.1 mm Hg, pulmonary vascular resistance (PVR) was 515.8 +/- 219.2
      dynes/s/cm5 and the median NT-proBNP level was 820 (153 to 1,871.5) ng/liter. At
      BL, World Health Organization functional class (FC) was >=III in 96.1% of the
      patients, whereas, at 6-MFU, 11.8% were in WHO FC >=III. At 6-MFU, mean PAP (32.6
      +/- 12.6 mm Hg; p < 0.001), PVR (396.9 +/- 182.6 dynes/s/cm5; p < 0.001) and NT
      proBNP (159.3 [84.4 to 464.3] ng/liter; p < 0.001) levels were reduced. The
      decrease in NT-proBNP levels correlated with the decrease in mean PAP (rrs =
      0.43, p = 0.002) and PVR (rrs = 0.50, p = 0.001). A reduction in the NT-proBNP
      level of 46% indicated a decrease in mean PAP of >=25% (area under the curve
      [AUC] = 0.71) and a reduction of 61% indicated a decrease in PVR of >=35% (AUC
      0.77). CONCLUSIONS: Our results demonstrate that NT-proBNP levels decrease after
      BPA, providing valuable evidence of procedural success. NT-proBNP measurement
      allows identification of patients who are BPA non-responders and may thus be a
      valuable adjunct in therapy monitoring.

PMID- 29329762
TI  - Smoking and HIV: confronting the epidemic.

PMID- 29329764
TI  - [Analysis of mortality and hospital stay in cardiac surgery in Mexico 2015: Data
      from the National Cardiology Institute].
AB  - OBJECTIVE: To analyse hospital mortality in patients subjected to cardiac surgery
      in Mexico during the year 2015, and identify the mortality risks factors, and its
      correlation with days of hospital stay in the cardiovascular intensive care unit.
      METHOD: The database of Cardiovascular Intensive Care of the National Institute
      of Cardiology was examined for this cases and controls study that included only
      adult patients subjected to cardiac surgery during the year 2015. RESULTS: A
      total of 571 patients were subjected to a surgical procedure. The predominant
      indication was single or multiple valve replacement surgery, followed by coronary
      revascularisation surgery, and correction of adult congenital heart disease.
      Overall mortality was 9.2, and 8% died in intensive care. The main risk factors
      for death were preoperative organ failure or pulmonary hypertension, and
      prolonged time with extracorporeal circulation. The primary cause of death was
      secondary to cardiogenic shock. The hospital mortality observed in this
      population was higher for patients undergoing pulmonary thromboendarterectomy,
      complex aortic disease surgery, and valvular surgery. CONCLUSIONS: The mortality
      of patients undergoing cardiac surgery in Mexico differs slightly from that
      reported in the world literature, primarily because there were more multivalvular
      surgeries and mixed complex procedures performed.

PMID- 29329765
TI  - Usefulness of the Trabecular Bone Score for assessing the risk of osteoporotic
      fracture.
AB  - INTRODUCTION AND OBJECTIVES: The trabecular bone score (TBS) is an imaging
      technique that assesses the condition of the trabecular microarchitecture.
      Preliminary results suggest that TBS, along with the bone mineral density
      assessment, could improve the calculation of the osteoporotic fracture risk. The
      aim of this study was to analyse TBS values and their relationship with the
      clinical characteristics, bone mineral density and history of fractures of a
      cohort of posmenopausal women. MATERIAL AND METHODS: We analysed 2,257
      posmenopausal women from the FRODOS cohort, which was created to determine the
      risk factors for osteoporotic fracture through a clinical survey and bone
      densitometry with vertebral morphometry. TBS was applied to the densitometry
      images. TBS values <=1230 were considered indicative of degraded
      microarchitecture. We performed a simple and multiple linear regression to
      determine the factors associated with this index. RESULTS: The mean TBS value in
      L1-L4 was 1.203+/-0.121. Some 55.3% of the women showed values indicating
      degraded microarchitecture. In the multiple linear regression analysis, the
      factors associated with low TBS values were age, weight, height, spinal T-score,
      glucocorticoid treatment, presence of type 2 diabetes and a history of fractures
      due to frailty. CONCLUSIONS: TBS showed microarchitecture degradation values in
      the participants of the FRODOS cohort and was associated with anthropometric
      factors, low bone mineral density values, the presence of fractures, a history of
      type 2 diabetes mellitus and the use of glucocorticoids.

PMID- 29329766
TI  - 77-year-old woman with pulse abnormalities.

PMID- 29329763
TI  - Efficacy and safety of varenicline for smoking cessation in people living with
      HIV in France (ANRS 144 Inter-ACTIV): a randomised controlled phase 3 clinical
      trial.
AB  - BACKGROUND: Tobacco smoking is common in people living with HIV, but high-quality
      evidence on interventions for smoking cessation is not available in this
      population. We aimed to assess the efficacy and safety of varenicline with
      counselling to aid smoking cessation in people living with HIV. METHODS: The ANRS
      144 Inter-ACTIV randomised, parallel, double-blind, multicentre, placebo
      controlled phase 3 trial was done at 30 clinical hospital sites in France. People
      living with HIV who had smoked at least ten cigarettes per day for 1 year or
      longer, were motivated to stop smoking, were not dependent on another
      psychoactive substance, and had no history of depression or suicide attempt were
      eligible. Using a computer-generated randomisation sequence, we allocated (1:1)
      the patients to receive either varenicline titrated to two 0.5 mg doses twice
      daily or placebo twice daily for 12 weeks, plus face-to-face counselling.
      Patients and investigators were masked to treatment group allocation. Patients
      who were not abstinent at week 24 were offered open-label varenicline for 12
      additional weeks. The primary outcome was the proportion of smokers continuously
      abstinent from week 9 to week 48. Smoking status was confirmed by carbon monoxide
      in exhaled air. Primary analyses were done in both the intention-to-treat (ITT)
      population and modified ITT (mITT) population, which comprised all patients who
      took at least one tablet of their assigned study treatment. The safety analyses
      were done in the mITT population. The trial is registered at ClinicalTrials.gov,
      number NCT00918307. The trial status is complete. FINDINGS: From Oct 26, 2009, to
      Dec 20, 2012, of 303 patients assessed for eligibility, 248 patients were
      randomly assigned to the varenicline group (n=123) or the placebo group (n=125).
      After randomisation, one participant initially assigned to the placebo group was
      excluded from the ITT analysis for a regulatory reason (no French health-care
      coverage). 102 patients in the varenicline group and 111 patients in the placebo
      group received at least one dose of their assigned treatment and were included in
      the mITT analysis. In the ITT analysis, varenicline was associated with a higher
      proportion of patients achieving continuous abstinence over the study period
      (week 9-48): 18 (15%, 95% CI 8-21) of 123 in the varenicline group versus eight
      (6%, 2-11) of 124 in the placebo group, adjusted odds ratio (OR) 2.5 (95% CI 1.0
      6.1; p=0.041). In the mITT analysis, varenicline was also associated with higher
      continuous abstinence: 18 (18%, 95% CI 10-25) of 102 versus eight (7%, 2-12) of
      111 in the placebo group (adjusted OR 2.7, 95% CI 1.1-6.5; p=0.029). The
      incidence of depression was 2.4 per 100 person-years (95% CI 0.6-9.5; two [2%] of
      102) in the varenicline group and 12.4 per 100 person-years (95% CI 6.9-22.5; 11
      [10%] of 111) in the placebo group. 14 (7%) of 213 participants had 18
      cardiovascular events: six (6%) of 102 people in the varenicline group and eight
      (7%) of 111 people in the placebo group. INTERPRETATION: Varenicline is safe and
      efficacious for smoking cessation in people living with HIV and should be
      recommended as the standard of care. FUNDING: The French National Institute for
      Health and Medical Research (INSERM)-French National Agency for Research on AIDS
      and Viral Hepatitis (ANRS) and Pfizer.

PMID- 29329767
TI  - Discussion.

PMID- 29329768
TI  - Management of pediatric ovarian torsion: evidence of follicular development after
      ovarian preservation.
AB  - PURPOSE: This study reviews contemporary management and follow-up of pediatric
      ovarian torsion. METHODS: This is a retrospective series of patients from birth
      to 19 years undergoing operative management of ovarian torsion from 2012 to 2016.
      RESULTS: We studied 43 girls who underwent 51 operations for ovarian torsion. The
      median age was 8.3 years. Ultrasound was utilized for diagnosis in 24/29 patients
      (83%) evaluated in a children's hospital. In contrast, computed tomography was
      used initially in 7 cases (50%) in children imaged at non-children's hospitals
      before transfer. Initial operation for ovarian torsion was completed
      laparoscopically in 38 (88%). Overall, ovarian preservation was performed in 37
      (86%) patients, while 6 (13%) underwent oophorectomy. Indications for
      oophorectomy included 5 infants with in utero torsion and an 18-year-old with a
      suspected malignancy. In girls with acute ovarian torsion, the oophorectomy rate
      was reduced to 2%. Postoperatively, 1 patient developed a small bowel obstruction
      requiring operation after laparoscopic ovarian detorsion. Recurrent torsion
      occurred in 3 patients (7%). In total, 34 patients underwent postoperative
      ovarian imaging. A total of 25 (74%) had follicles visualized in the previously
      torsed ovary. CONCLUSION: Ovarian-sparing operations for acute torsion are safe
      and result in ovarian salvage and preservation of follicular development in more
      than 70% of children and adolescents.

PMID- 29329769
TI  - Erratum to "Absorption, liver first-pass effect, pharmacokinetics and tissue
      distribution of calycosin-7-O-beta-d-glucopyranoside (C7G) and its major active
      metabolite, calycosin, following oral administration of C7G in rats by LC-MS/MS"
      [J. Pharm. Biomed. Anal. 148 (2018) 350-354].

PMID- 29329770
TI  - Yield of family screening in patients with isolated bicuspid aortic valve in a
      general hospital.
AB  - AIM: To determine the prevalence of unidentified bicuspid aortic valve (BAV) or
      aortic dilatation (>40mm) in first degree relatives (FDR) of patients with
      isolated BAV in a general hospital. METHODS AND RESULTS: Patients with isolated
      BAV received information advising cardiac screening of their FDR. Referred and
      screened were 134 FDR of 54 adult index patients with isolated BAV (median 2 per
      index patient). FDR's mean age was 49years (range 16-83years) and 41% were male.
      They comprised 5 parents (3.7%), 52 siblings (39%) and 77 offspring (57%). Among
      these FDR, the prevalence of BAV was 6.0% (8 patients). In FDR without BAV, 10
      (7.5%) had aortic dilatation. 'Familial BAV' was present in 9/54 families (17%).
      CONCLUSION: In a general hospital, screening of FDR of patients with isolated BAV
      resulted in a substantial yield of 13% new cases with BAV or aortic dilatation
      without BAV.

PMID- 29329771
TI  - Low rate of revascularization procedures and poor prognosis particularly in male
      patients with peripheral artery disease - A propensity score matched analysis.
AB  - BACKGROUND: Few data discuss the impact of sex on diagnostic and therapeutic
      procedures and outcome of patients with peripheral artery disease (PAD). METHODS:
      We obtained data on 41,873 PAD patients between 2009 and 2011 (including a 4-year
      follow-up) from the largest German public health insurance (BARMER GEK).
      Propensity Score Matching (PSM) was performed to evaluate the impact of sex on
      treatment, complications, in-hospital and long-term outcome. RESULTS: Of 41,873
      PAD patients, there were 23,282 (55.6%) male and 18,591 (44.4%) female. Male
      patients were younger (69+/-11years vs. 75+/-12years in females; p<0.001) but had
      higher obesity (8.0% vs 6.5%), dyslipidemia (33.2% vs 28.1%), smoking (12.9% vs
      9.2%), coronary artery disease (29.4% vs 19.5%), or diabetes rates (35.8% vs
      28.1%; each p<0.001). Almost three in five revascularizations applied to minor
      clinical stages, revascularization rate in critical limb ischemia (CLI) was 49%
      at in-hospital and 58.8% inc. follow-up in both sexes (Rutherford 6). PSM
      accounting for risk factors and PAD stages showed lower use of endovascular and
      higher use of surgical revascularization in males compared to females. Male sex
      was associated with higher in-hospital amputation and was an independent risk
      factor during follow-up for both amputation (HR 1.284; p<0.001) and death (HR
      1.155; p<0.001). CONCLUSIONS: Data show low rates of revascularization procedures
      particularly at advanced PAD stages (CLI). Male sex is associated with higher use
      of surgical, but lower use of endovascular and overall procedures, and higher
      amputation and mortality during follow-up.

PMID- 29329772
TI  - Robust decentralized controller for minimizing coupling effect in single inductor
      multiple output DC-DC converter operating in continuous conduction mode.
AB  - This paper describes a novel robust decentralized control design methodology for
      a single inductor multiple output (SIMO) DC-DC converter. Based on a nominal
      multiple input multiple output (MIMO) plant model and performance requirements, a
      pairing input-output analysis is performed to select the suitable input to
      control each output aiming to attenuate the loop coupling. Thus, the plant
      uncertainty limits are selected and expressed in interval form with parameter
      values of the plant model. A single inductor dual output (SIDO) DC-DC buck
      converter board is developed for experimental tests. The experimental results
      show that the proposed methodology can maintain a desirable performance even in
      the presence of parametric uncertainties. Furthermore, the performance indexes
      calculated from experimental data show that the proposed methodology outperforms
      classical MIMO control techniques.

PMID- 29329774
TI  - Enzymatic saccharification of lignocellulosic biorefinery: Research focuses.
AB  - To realize lignocellulosic biorefinery is of global interest, with enzymatic
      saccharification presenting an essential stage to convert polymeric sugars to
      mono-sugars for fermentation use. This mini-review summarizes qualitatively the
      research focuses discussed the review articles presented in the past 22 months
      and other relevant papers. The research focuses on pretreatment with improved
      efficiency, enhanced enzyme production with high yields and high extreme
      tolerance, feasible combined saccharification and fermentation processes,
      detailed mechanisms corresponding to the enzymatic saccharification in
      lignocellulosic biorefinery, and the costs are discussed.

PMID- 29329773
TI  - Total energy expenditure and body composition of children with developmental
      disabilities.
AB  - BACKGROUND: Obesity prevalence is increased in children with developmental
      disabilities, specifically in children with spina bifida and Down syndrome.
      Energy expenditure, a critical aspect of weight management, has been extensively
      studied in the typically developing population, but not adequately studied in
      children with developmental disabilities. OBJECTIVE: Determine energy
      expenditure, fat-free mass and body fat percentile and the impact of these
      findings on recommended caloric intake in children with spina bifida and Down
      syndrome. METHODS/MEASURES: This pilot study included 36 children, 18 with spina
      bifida, 9 with Down syndrome and 9 typically developing children. Half of the
      children with spina bifida were non-ambulatory. Doubly labeled water was used to
      measure energy expenditure and body composition. Descriptive statistics described
      the sample and MANOVA and ANOVA methods were used to evaluate differences between
      groups. RESULTS: Energy expenditure was significantly less for children with
      spina bifida who primarily used a wheelchair (p = .001) and children with Down
      syndrome (p = .041) when compared to children without a disability when adjusted
      for fat-free mass. However, no significant difference was detected in children
      with spina bifida who ambulated without assistance (p = .072). CONCLUSIONS:
      Children with spina bifida and Down syndrome have a significantly decreased
      energy expenditure which directly impacts recommended caloric intake. No
      significant difference was detected for children with spina bifida who ambulated,
      although the small sample size of this pilot study may have limited these
      findings. Validating these results in a larger study is integral to supporting
      successful weight management of these children.

PMID- 29329775
TI  - Recent advances and strategies in process and strain engineering for the
      production of butyric acid by microbial fermentation.
AB  - Butyric acid is an important platform chemical, which is widely used in the
      fields of food, pharmaceutical, energy, etc. Microbial fermentation as an
      alternative approach for butyric acid production is attracting great attention as
      it is an environmentally friendly bioprocessing. However, traditional
      fermentative butyric acid production is still not economically competitive
      compared to chemical synthesis route, due to the low titer, low productivity, and
      high production cost. Therefore, reduction of butyric acid production cost by
      utilization of alternative inexpensive feedstock, and improvement of butyric acid
      production and productivity has become an important target. Recently, several
      advanced strategies have been developed for enhanced butyric acid production,
      including bioprocess techniques and metabolic engineering methods. This review
      provides an overview of advances and strategies in process and strain engineering
      for butyric acid production by microbial fermentation. Additionally, future
      perspectives on improvement of butyric acid production are also proposed.

PMID- 29329776
TI  - Sequential dark and photo fermentation hydrogen production from hydrolyzed corn
      stover: A pilot test using 11 m3 reactor.
AB  - Pilot tests of sequential dark and photo fermentation H2 production were for the
      first time conducted in a 11 m3 reactor (3 m3 for dark and 8 m3 for photo
      compartments). A combined solar and light-emitting diode illumination system and
      a thermal controlling system was installed and tested. With dark fermentation
      unit maintained at pH 4.5 and 35  degrees C and photo fermentation unit at pH 7.0
      and 30  degrees C, the overall biogas production rate using hydrolyzed corn
      stover as substrate reached 87.8 +/- 3.8 m3/d with 68% H2 content, contributed by
      dark unit at 7.5 m3-H2/m3-d and by photo unit at 4.7 m3/m3-d. Large variation was
      noted for H2 production rate in different compartments of the tested units,
      revealing the adverse effects of poor mixing, washout, and other inhomogeneity
      associated with large reactor operations.

PMID- 29329777
TI  - Dietary intake by food group of individuals with type 2 diabetes mellitus: A
      systematic review.
AB  - AIMS: To synthesize peer-reviewed literature that investigates the dietary intake
      by food group of individuals with type 2 diabetes mellitus (T2DM) and compare
      intakes to national and international dietary guidelines. METHODS: Four
      electronic databases (MEDLINE, EMBASE, CINAHL and Web of Sciences) were searched
      for studies that investigated the dietary intake of adults (>=18 years) with T2DM
      using the five main food groups (fruit, vegetables, dairy, grains and meat/meat
      alternatives). Food group intake in serves was compared against national
      guidelines and fruit and vegetable intake in grams was compared against the World
      Health Organization (WHO) guidelines. RESULTS: After screening 13,662
      publications, 11 studies were included. All reported cross-sectional data.
      Majority of participants were consuming less than the recommended serves of
      fruit, vegetables, grains and dairy and were meeting or exceeding the recommended
      serves for meat/meat alternatives. Two of six studies reported fruit and
      vegetable recommendations were being met, two reported dairy recommendations were
      being met and two reported grain recommendations were being met. Of the five
      studies reporting intake in grams, four met the WHO minimum intake for fruit and
      vegetables. CONCLUSIONS: Individuals with T2DM do not comply with food group
      recommendations; particularly for fruit, vegetables, dairy and grains.
      Longitudinal research is required to better understand how food group intake
      changes over time after diagnosis.

PMID- 29329778
TI  - High-intensity interval training versus continuous training on physiological and
      metabolic variables in prediabetes and type 2 diabetes: A meta-analysis.
AB  - AIMS: To compare the effects of high-intensity interval training (HIIT) versus
      moderate-intensity continuous training (MICT) on functional capacity and
      cardiometabolic markers in individuals prediabetes and type 2 diabetes (T2D).
      METHODS: The search was performed in PubMed (MEDLINE), EMBASE, PEDro, CENTRAL,
      Scopus, LILACS database, and Clinical Trials from the inception to July 2017,
      included randomized clinical trials that compared the use of HIIT and MICT in
      prediabetes and T2D adults. The risk of bias was defined by Cochrane Handbook and
      quality of evidence by GRADE. RESULTS: From 818 relevant records, seven studies
      were included in systematic review (64 prediabetes and 120 T2D patients) and five
      with T2D were meta-analyzed. HIIT promoted significantly increased of 3.02
      mL/kg/min (CI95% 1.42-4.61) of VO2max, measured for functional capacity, compared
      to MICT. No differences were found between two modalities of exercises
      considering the outcomes HbA1c, systolic and diastolic blood pressure, total
      cholesterol, HDL and LDL cholesterol, triglycerides, BMI, and waist-to-hip ratio.
      Most of the studies presented unclear risk of bias, and low and very low quality
      of evidence. CONCLUSION: HIIT induces cardiometabolic adaptations similar to
      those of MICT in prediabetes and T2D, and provides greater benefits to functional
      capacity in patients with T2D. PROSPERO: CRD42016047151.

PMID- 29329779
TI  - Receptor- and cellular compartment-specific activation of the cAMP/PKA pathway by
      alpha1-adrenergic and ETA endothelin receptors.
AB  - The signalling functions of many G protein-coupled receptors (GPCRs) expressed in
      the myocardium are incompletely understood. Among these are the endothelin
      receptor (ETR) family and alpha1-adrenergic receptor (alpha1-AR), which are
      thought to couple to the G protein Galphaq. In this study, we used transcriptome
      analysis to compare the signalling networks downstream of these receptors in
      primary neonatal rat cardiomyocytes. This analysis indicated increased expression
      of target genes of cAMP responsive element modulator (CREM) after 24 h treatment
      with the alpha1-AR agonist phenylephrine, but not the ETR agonist endothelin-1,
      suggesting a specific role for the alpha1-AR in promoting cAMP production in
      cardiomyocytes. To validate the difference observed between these two GPCRs, we
      used heterologous expression of the receptors and genetically encoded biosensors
      in HEK 293 cell lines. We validated that both alpha1A- and alpha1B-AR subtypes
      were able to lead to the accumulation of cAMP in response to phenylephrine in
      both the nucleus and cytoplasm in a Galphas-dependent manner. However, the ETR
      subtype ETA did not affect cAMP levels in either compartment. All three receptors
      were coupled to Galphaq signalling as expected. Further, we showed that
      activation of PKA in different compartments was alpha1-AR subtype specific, with
      alpha1B-AR able to activate PKA in the cytoplasm and nucleus and alpha1A-AR only
      able to in the nucleus. We provide evidence for a pathway downstream of the
      alpha1-AR, and show that distinct pools of a receptor lead to differential
      activation of downstream effector proteins dependent on their cellular
      compartment.

PMID- 29329780
TI  - Oncogenic RAC1 and NRAS drive resistance to endoplasmic reticulum stress through
      MEK/ERK signalling.
AB  - Cancer cells are able to survive under conditions that cause endoplasmic
      reticulum stress (ER-stress), and can adapt to this stress by upregulating cell
      survival signalling pathways and down-regulating apoptotic pathways. The cellular
      response to ER-stress is controlled by the unfolded protein response (UPR). Small
      Rho family GTPases are linked to many cell responses including cell growth and
      apoptosis. In this study, we investigate the function of small GTPases in cell
      survival under ER-stress. Using siRNA screening we identify that RAC1 promotes
      cell survival under ER-stress in cells with an oncogenic N92I RAC1 mutation. We
      uncover a novel connection between the UPR and N92I RAC1, whereby RAC1 attenuates
      phosphorylation of EIF2S1 under ER-stress and drives over-expression of ATF4 in
      basal conditions. Interestingly, the UPR connection does not drive resistance to
      ER-stress, as knockdown of ATF4 did not affect this. We further investigate
      cancer-associated kinase signalling pathways and show that RAC1 knockdown reduces
      the activity of AKT and ERK, and using a panel of clinically important kinase
      inhibitors, we uncover a role for MEK/ERK, but not AKT, in cell viability under
      ER-stress. A known major activator of ERK phosphorylation in cancer is oncogenic
      NRAS and we show that knockdown of NRAS in cells, which bear a Q61 NRAS mutation,
      sensitises to ER-stress. These findings highlight a novel mechanism for
      resistance to ER-stress through oncogenic activation of MEK/ERK signalling by
      small GTPases.

PMID- 29329781
TI  - Dopamine transporter trafficking is regulated by neutral sphingomyelinase
      2/ceramide kinase.
AB  - Dopamine (DA) reuptake is the primary mechanism to terminate dopaminergic
      transmission in the synaptic cleft. The dopamine transporter (DAT) has an
      important role in the regulation of DA reuptake. This study provides anatomical
      and physiological evidence that DAT recycling is regulated by ceramide kinase via
      the sphingomyelin pathway. First, the results show that DAT and neutral
      sphingomyelinase 2 (nSMase2) were successfully co-precipitated from striatal
      samples and were colocalized in the mouse striatum or PC12 cells. We also
      identified a protein-protein interaction between nSMase2 and DAT through in situ
      proximity ligation assay experiments in the mouse striatum. Second, dopamine (DA)
      stimulated the formation of ceramide and increased nSMase activity in PC12 cells,
      while treatment with a cell-permeable ceramide-1-phosphate (C1P) increased DA
      uptake. Third, we used inhibitors and siRNA to inhibit nSMase2 and ceramide
      kinase and observed the effects on DAT recycling in PC12 cells. Treatment with
      ceramide kinase inhibitor K1, or nSMase inhibitor GW4869, decreased DA uptake in
      PC12 cells, although the application of FB1, a ceramide synthase inhibitor, did
      not affect DA uptake. Transfection of nSMase2 and CERK siRNA decreased DAT
      surface level in PC12 cells. These results suggested that SM-derived C1P affects
      cell surface levels of DAT.

PMID- 29329782
TI  - LPA-induced migration of ovarian cancer cells requires activation of ERM proteins
      via LPA1 and LPA2.
AB  - Lysophosphatidic acid (LPA) has been implicated in the pathology of human ovarian
      cancer. This phospholipid elicits a wide range of cancer cell responses, such as
      proliferation, trans-differentiation, migration, and invasion, via various G
      protein-coupled LPA receptors (LPARs). Here, we explored the cellular signaling
      pathway via which LPA induces migration of ovarian cancer cells. LPA induced
      robust phosphorylation of ezrin/radixin/moesin (ERM) proteins, which are membrane
      cytoskeleton linkers, in the ovarian cancer cell line OVCAR-3. Among the LPAR
      subtypes expressed in these cells, LPA1 and LPA2, but not LPA3, induced
      phosphorylation of ERM proteins at their C-termini. This phosphorylation was
      dependent on the Galpha12/13/RhoA pathway, but not on the Galphaq/Ca2+/PKC or
      Galphas/adenylate cyclase/PKA pathway. The activated ERM proteins mediated
      cytoskeletal reorganization and formation of membrane protrusions in OVCAR-3
      cells. Importantly, LPA-induced migration of OVCAR-3 cells was completely
      abolished not only by gene silencing of LPA1 or LPA2, but also by overexpression
      of a dominant negative ezrin mutant (ezrin-T567A). Taken together, this study
      demonstrates that the LPA1/LPA2/ERM pathway mediates LPA-induced migration of
      ovarian cancer cells. These findings may provide a potential therapeutic target
      to prevent metastatic progression of ovarian cancer.

PMID- 29329783
TI  - Comparative genome based cis-elements analysis in the 5' upstream and 3'
      downstream region of cell wall invertase and Phenylalanine ammonia lyase in
      Nicotiana benthamiana.
AB  - Plant secondary metabolites are widely used in human disease treatment; though
      primary metabolism provides precursors for secondary metabolism, not much has
      been studied to unravel the link connecting both the processes. Most common form
      of gene regulation interconnecting diverse metabolism occurs at the
      transcriptional and/or posttranscriptional level mediated by regulatory cis
      elements. The present study aims at understanding the common cis-elements network
      connecting the major primary metabolic enzyme, cell wall invertase (CWIN) and
      secondary metabolism genes in Nicotiana benthamiana (N. benthamiana). The CWIN
      and thirty one other gene sequences were extracted from N. benthamiana genome,
      followed by cis-element analysis of their 5' upstream and 3' downstream region
      using different programs (Genomatix software suite; PLACE and PlantCARe).
      Comparative cis-element analysis of CWIN (N. benthamiana and other plant species)
      and other primary, secondary metabolism and transcription factor genes (N.
      benthamiana) revealed the occurrence of common stress associated cis-elements.
      Predominantly, AHBP, L1BX, MYBL, MADS, MYBS, GTBX, DOFF and CCAF were found in
      the 5' upstream region of all genes, whereas AHBP, MYBL, L1BX, HEAT, CCAF and
      KAN1 were largely occurring in the 3' downstream region of all genes; indicating
      common function of these elements in transcriptional and posttranscriptional gene
      regulation. Further, genomic analysis using FGENESH, GenScan and homology based
      methods (BlastX and BlastN) was performed on the N. benthamiana contigs harboring
      CWIN and PAL, in an attempt to identify genomic neighborhood genes. The 5'
      upstream and 3' downstream region of genes in the genomic neighborhood of CWIN
      and PAL were also subjected to similar cis-element analysis, and the results
      indicated cis-elements profile similar to CWIN, PAL and other primary, secondary
      metabolism and transcription factor genes. The results of evolutionary studies
      confirmed that the 5' upstream region of NbCWINs significantly showed more
      proximity to secondary metabolism genes 4CL and the redox gene SOD, followed by
      the phenylpropanoid pathway gene CHI. The 3' downstream regions of NbCWINs were
      more closely related to other plant CWINs, followed by the redox gene, SOD and
      primary metabolism gene FBA. Thus, the commonly found stress responsive cis
      elements in our study can play a vital role in modulating key pathways of both
      primary and secondary metabolism; thereby postulating their role in regulating
      plant growth and metabolisms under unfavourable growth conditions.

PMID- 29329784
TI  - Regulatory Science - An Underappreciated Component of Translational Research.
AB  - Translational science refers to translating basic scientific findings to
      practical application (i.e., 'bench-to-bedside'). An underappreciated aspect of
      translational science is regulatory science. Herein, we focus on the importance
      of regulatory science to facilitate development of innovative new drugs and
      optimize use of approved drugs, with a call for community participation.

PMID- 29329785
TI  - A relapsing fever group Borrelia sp. is widely distributed among wild deer in
      Japan.
AB  - A relapsing fever group Borrelia sp. was detected from the blood of wild deer
      (Cervus nippon) in Japan. The Borrelia sp. was distributed nationwide among deer
      with an overall prevalence of 26% in blood samples. The prevalence of infection
      was significantly higher in fawns (48.4%) compared to adult deer (23.6%).
      Sequencing analysis reveals that this Borrelia sp. belongs to the hard tick-borne
      relapsing fever borreliae, and that it forms a single lineage based on sequences
      of the flagellin and glycerophosphodiester phosphodiesterase genes. Borrelial
      genome copy number was estimated at 8.8 * 103 genome copies/MUl of blood. Other
      hard tick-borne relapsing fever borrelia (e.g. Borrelia miyamotoi) were not
      detected in deer blood in this study. These findings suggest that wild deer may
      act as reservoirs for this Borrelia sp. in Japan.

PMID- 29329786
TI  - Clinicopathological and prognostic significance of lymphocyte to monocyte ratio
      in patients with gastric cancer: A meta-analysis.
AB  - BACKGROUND: Recently, the lymphocyte-to-monocyte ratio (LMR) has been reported to
      be a prognostic factor in multiple malignancies. The current study was designed
      to assess the prognostic value of pretreatment LMR in gastric cancer (GC).
      METHODS: MEDLINE, EMBASE, Cochrane, and CNKI databases were searched until April
      2017. Eligible articles were defined as studies assessing the prognostic role of
      pretreatment LMR in GC. Pooled hazard ratios (HRs) for overall survival (OS),
      disease-free survival (DFS), and recurrence-free survival (RFS) were calculated
      using fixed-effects or random-effects models. RESULTS: A total of six studies
      comprising 4908 patients were included in the study. Pooled results showed that
      low LMR was significantly associated with decreased OS (HR: 0.66, 95% confidence
      interval [CI]: 0.54-0.82, p < .001), but not with poor DFS/RFS (HR: 0.71, 95% CI:
      0.38-1.32, p = .004). The unfavorable prognostic impact of low LMR on OS was
      observed in patients of different disease stages and cut-off values. Moreover,
      low LMR was significantly related to age (>median), gender (male), CEA (>5
      ng/ml), tumor size (>3 cm), TNM stage (III-IV), lymph node metastasis, and
      distant metastasis. CONCLUSIONS: Low pretreatment LMR may be a significant
      prognostic biomarker for poor OS in patients with GC.

PMID- 29329787
TI  - Outcomes of multisegmental transforaminal enlarged decompression plus posterior
      pedicle screw fixation for multilevel lumbar spinal canal stenosis associated
      with lumbar instability.
AB  - PURPOSE: The aim of this study was to evaluate the clinical and radiologic
      results of multisegmental transforaminal enlarged decompression (TED) plus
      posterior pedicle screw fixation in the treatment of multilevel lumbar spinal
      canal stenosis (LSCS) with lumbar instability (MLSCSI). METHODS: 113 patients
      with MLSCSI underwent surgery were recruited in this study. All patients were
      suffering from symptoms typical of degenerative LSCS and treated with either TED
      plus fusion (TEDF group) or conventional laminectomy plus fusion (CLF group).
      Clinical and radiologic parameters were evaluated. The clinical data, including
      Visual Analog Scale (VAS) for back and leg pain, Oswestry Disability Index (ODI),
      operative time, intraoperative blood loss, postoperative drainage, hospital stay,
      and the rate of postoperative complications, were assessed. With respect to
      radiologic parameters, mean disc height (MDH) and lumbar lordotic angle (LLA)
      were measured using plain radiographs. Patient satisfaction was evaluated
      according to the North American Spine Society (NASS) Outcome Questionnaire.
      RESULTS: No serious complications occurred during the follow-up. The operative
      time was significantly shorter for TEDF group than for CLF group, and similar
      results were found with regard to the blood loss and postoperative drainage (p <
      .05). The improvements in ODI, leg and back VAS scores were observed in both
      groups after surgery and follow-up (P < .05). In the last follow-up, ODI and back
      VAS scores in TEDF group were significantly higher than those in CLF group (P <
      .05). Regarding radiologic variants, MDH and LLA were improved after operation
      for 3 months (P > .05) and were all well maintained in the final follow-up in
      both groups. Patients in TEDF group were more satisfied than patients in the CLF
      group (85.2% vs 76.9%, p = .092). CONCLUSIONS: Satisfactory clinical and
      radiological outcomes can be achieved with the use of multisegmental TED plus
      lumbar fusion for the treatment of MLSCSI. This technique can reduce surgically
      induced instability and obviously improve the symptoms and signs of the patients,
      suggesting a safe and effective therapeutic procedure for MLSCSI.

PMID- 29329788
TI  - Effect of individualized distal femoral valgus resection angle in primary total
      knee arthroplasty: A systematic review and meta-analysis involving 1300 subjects.
AB  - BACKGROUND: Proper limb alignment and implant positioning are important for
      successful total knee arthroplasty (TKA). Whether any differences exist in
      restoration of limb alignment for valgus knees between fixed and individual
      femoral valgus correction angle (VCA) for distal femoral resection remains
      unknown. METHODS: The PubMed, Medline, Embase, and Wangfang databases were
      searched to identify studies comparing individualized VCA and fixed VCA in the
      distal femoral valgus resection. The primary outcomes were the mechanical
      femorotibial angle (MFT angle) and the proportion of postoperative alignment
      deviation within +/-3 degrees . The secondary outcomes were femoral valgus
      correction angle (VCA), component angle (alpha angle and beta angle). RESULTS:
      Six studies with 1167 TKAs were analyzed quantitatively. The coronal limb
      alignments in individualized group were closer to neutral than fixed group with a
      mean 0.77 degrees  difference (95% CI, -1.43 to -0.11; P = .022; I2 = 71.0%).
      Moreover, there were more patients' postoperative alignment deviation within
      neutral +/-3 degrees  in the individualized group (RR, 1.23; 95% CI, 1.09 to
      1.38; P = .00; I2 = 36.4%). The alpha angle were closer to neutral in the
      individualized group, and there's 1.2 degrees  more deviation from neutral in the
      fixed group (95% CI, 0.99 to 1.41; P = .00; I2 = 0%). No difference was found in
      the beta angle between groups (WMD, 0.85; 95% CI, -0.09 to 1.78; P = .075; I2 =
      88.3%). CONCLUSIONS: This systematic review and meta-analysis demonstrated that
      the individualized VCA for distal femoral resection could enhance the accuracy of
      postoperative limb alignment and femoral component alignment in the coronal
      plane. However, further high-quality RCTs and well-designed trials are still
      needed.

PMID- 29329789
TI  - Lateral lymph node metastasis in papillary thyroid carcinoma: A systematic review
      and meta-analysis for prevalence, risk factors, and location.
AB  - BACKGROUND: Lymph node metastasis (LNM) is frequent in papillary thyroid
      carcinoma (PTC) and is associated with a poor prognosis. Unlike central LNM
      (CLNM), there are few studies focusing on LLNM. We aimed to investigate the
      prevalence and the risk factors for LLNM, with its most prevalent sites. METHODS:
      We performed a comprehensive literature search using the PubMed and EMBASE
      databases for relevant studies published prior to November 2016 that examined the
      risk factors for LLNM. RESULTS: Twenty-three studies, including 18,741 patients,
      were included. The prevalence of LLNM was 20.9% in all patients. CLNM (pooled OR
      = 7.84, 95% CI = 6.13-10.02, p < .0001), extrathyroidal extension (pooled OR =
      3.22, 95% CI = 2.21-4.70, p < .0001), tumor multifocality (pooled OR = 2.19, 95%
      CI = 1.67-2.89, p < .0001), male sex (pooled OR = 1.72, 95% CI = 1.50-1.98, p <
      .0001), upper pole location (pooled OR = 2.96, 95% CI = 1.93-4.53, p < .0001),
      tumor size >=1.0 cm (pooled OR = 2.49, 95% CI = 1.71-3.61, p < .0001),
      lymphovascular invasion (pooled OR = 3.96, 95% CI = 2.61-6.03, p < .0001) and
      tumor bilaterality (pooled OR = 1.31, 95% CI = 1.12-1.53, p = .0006) were
      significantly associated with LLNM. Most frequently affected areas were levels
      III and IV. CONCLUSIONS: The prevalence of LLNM was high although the prognostic
      impact is unknown. The significant risk factors for LLNM were not much different
      from known risk factors for CLNM.

PMID- 29329790
TI  - Plant-derived mPGES-1 inhibitors or suppressors: A new emerging trend in the
      search for small molecules to combat inflammation.
AB  - Inflammation comprises the reaction of the body to injury, in which a series of
      changes of the terminal vascular bed, blood, and connective tissue tends to
      eliminate the injurious agent and to repair the damaged tissue. It is a complex
      process, which involves the release of diverse regulatory mediators. The current
      anti-inflammatory agents are challenged by multiple side effects and thus, new
      effective therapies are highly needed. The aim of this review is to summarize the
      described microsomal prostaglandin E synthase-1 (mPGES-1) inhibitors or
      transcriptional suppressors from medicinal plants, which could be an ideal
      approach in the management of inflammatory disorders, but need further clinical
      trials in order to be ultimately validated.

PMID- 29329791
TI  - Corrigendum to "Bcl xL deamidation and cancer: Charting the fame trajectories of
      legitimate child and hidden siblings." [Biochim. Biophys. Acta 1864/10 (2017)
      1734-1745].

PMID- 29329792
TI  - [Implementation of a health promotion programme for women in social exclusion in
      the city of Seville (Spain)].
AB  - Health promotion can contribute towards reducing inequality and ensuring equal
      opportunities, providing the means to enable the entire population to develop its
      maximum health possibilities. Women living in areas with social transformation
      needs (ASTN) are an especially vulnerable group due to the situation of material
      deprivation and social exclusion in which they live. Health promotion programmes
      for this group can bring about an improvement in their health. This paper
      describes the health promotion programme Socio-educational Groups of Primary Care
      for Women (SEGPC-W), and evaluates its implementation in ASTN in the city of
      Seville (Spain), as well as the benefits and difficulties of its development
      through a documentary analysis and interviews with participating professionals.

PMID- 29329793
TI  - Drug use, family support and related factors in university students. A cross
      sectional study based on the uniHcos Project data.
AB  - OBJECTIVE: To assess the prevalence of illegal drug use in college students on
      any previous occasion, during the previous year and the previous month, and to
      analyze the relationship between illegal drug use and family support and other
      factors. METHODS: A cross-sectional study using data from students participating
      in the uniHcos project (n = 3767) was conducted. The prevalence and age of onset
      of consumption of cannabis, non-prescription sedatives, stimulants and
      depressants was evaluated. Polyconsumption was also assessed. The independent
      variables were: family support, age, residence, and employment status. To
      determine the factors related to drug use multivariate logistic regression models
      stratified by gender were fitted. RESULTS: Differences between men and women in
      prevalence of illegal drug use except non-prescription sedatives were observed.
      In both genders, less family support was associated with higher consumption of
      all drugs, except depressants, and with polyconsumption. To be studying and
      looking for work was related to cannabis and stimulant use and to polyconsumption
      among women, but only to cannabis use among men. CONCLUSIONS: These results
      support the notion that the start of university studies is a particularly
      relevant stage in the onset of illegal drug use and its prevention, and that
      consumption may be especially associated with family support.

PMID- 29329794
TI  - Redox-signals and macrophage biology.
AB  - Macrophages are known for their versatile role in biology. They sense and clear
      structures that contain exogenous or endogenous pathogen-associated molecular
      patterns. This process is tightly linked to the production of a mixture of
      potentially harmful oxidants and cytokines. Their inherent destructive behavior
      is directed against foreign material or structures of 'altered self', which
      explains the role of macrophages during innate immune reactions and inflammation.
      However, there is also another side of macrophages when they turn into a tissue
      regenerative, pro-resolving, and healing phenotype. Phenotype changes of
      macrophages are termed macrophage polarization, representing a continuum between
      classical and alternative activation. Macrophages as the dominating producers of
      superoxide/hydrogen peroxide and nitric oxide are not only prone to oxidative
      modifications but also to more subtle signaling properties of redox-active
      molecules conveying redox regulation. We review basic concepts of the enzymatic
      nitric oxide and superoxide production within macrophages, refer to their unique
      chemical reactions and outline biological consequences not only for macrophage
      biology but also for their communication with cells in the microenvironment.
      These considerations link hypoxia to the NO system, addressing feedforward as
      well as feedback circuits. Moreover, we summarize the role of redox-signaling
      affecting epigenetics and reflect the central role of mitochondrial-derived
      oxygen species in inflammation. To better understand the diverse functions of
      macrophages during initiation as well as resolution of inflammation and to decode
      their versatile roles during innate and adaptive immunity with the entire
      spectrum of cell protective towards cell destructive activities we need to
      appreciate the signaling properties of redox-active species. Herein we discuss
      macrophage responses in terms of nitric oxide and superoxide formation with the
      modulating impact of hypoxia.

PMID- 29329795
TI  - Omega-3 fatty acids and adipose tissue biology.
AB  - This review provides evidence for the importance of white and brown adipose
      tissue (i.e. WAT and BAT) function for the maintenance of healthy metabolic
      phenotype and its preservation in response to omega-3 polyunsaturated fatty acids
      (omega-3 PUFA), namely in the context of diseased states linked to aberrant
      accumulation of body fat, systemic low-grade inflammation, dyslipidemia and
      insulin resistance. More specifically, the review deals with (i) the concept of
      immunometabolism, i.e. how adipose-resident immune cells and adipocytes affect
      each other and define the immune-metabolic interface; and (ii) the characteristic
      features of "healthy adipocytes" in WAT, which are relatively small fat cells
      endowed with a high capacity for mitochondrial oxidative phosphorylation,
      triacylglycerol/fatty acid (TAG/FA) cycling and de novo lipogenesis (DNL). The
      intrinsic metabolic features of WAT and their flexible regulations, reflecting
      the presence of "healthy adipocytes", provide beneficial local and systemic
      effects, including (i) protection against in situ endoplasmic reticulum stress
      and related inflammatory response during activation of adipocyte lipolysis; (ii)
      prevention of ectopic fat accumulation and dyslipidemia caused by increased
      hepatic VLDL synthesis, as well as prevention of lipotoxic damage of insulin
      signaling in extra-adipose tissues; and also (iii) increased synthesis of anti
      inflammatory and insulin-sensitizing lipid mediators with pro-resolving
      properties, including the branched fatty acid esters of hydroxy fatty acids
      (FAHFAs), also depending on the activity of DNL in WAT. The "healthy adipocytes"
      phenotype can be induced in WAT of obese mice in response to various stimuli
      including dietary omega-3 PUFA, especially when combined with moderate calorie
      restriction, and possibly also with other life style (e.g. physical activity) or
      pharmacological (e.g. thiazolidinediones) interventions. While omega-3 PUFA could
      exert beneficial systemic effects by improving immunometabolism of WAT without a
      concomitant induction of BAT, it is currently not clear whether the metabolic
      effects of the combined intervention using omega-3 PUFA and calorie restriction
      or thiazolidinediones depend also on the activation of BAT function and/or the
      induction of brite/beige adipocytes in WAT. It remains to be established why
      omega-3 PUFA intervention in type 2 diabetic subjects does not improve insulin
      sensitivity and glucose homeostasis despite inducing various anti-inflammatory
      mediators in WAT, including the recently discovered docosahexaenoyl esters of
      hydroxy linoleic acid, the lipokines from the FAHFA family, as well as several
      endocannabinoid-related anti-inflammatory lipids. To answer the question whether
      and to which extent omega-3 PUFA supplementation could promote the formation of
      "healthy adipocytes" in WAT of human subjects, namely in the obese insulin
      resistant patients, represents a challenging task that is of great importance for
      the treatment of some serious non-communicable diseases.

PMID- 29329796
TI  - The Evolving Face of Myocardial Reperfusion in Acute Coronary Syndromes: A Primer
      for the Internist.
AB  - Acute coronary syndromes (ACSs) account for a large proportion of disease burden
      in the United States and worldwide, and our understanding of ACS management
      continues to evolve. In this review we take a practical approach to evaluating
      and treating a patient with ACS, focusing on the optimal timing and methods of
      coronary reperfusion. Beginning with initial assessment and risk stratification,
      a provider managing the patient with ACS must be able to expeditiously decide on
      and implement the correct guideline-directed pathway to optimize outcomes. With
      an ever-growing body and weight of knowledge in this field, the clinician is
      tasked with several challenges. First, there are a variety of pathways of care to
      be considered; second, adjunctive medical therapies are expanding; and third,
      when coupled with the multiple combinations of adjunctive supportive therapies
      for revascularization, the variety of potential therapeutic options can be
      overwhelming and confusing. Herein, we carefully review all the relevant
      guidelines and the contributing literature, taking a 4-step approach: (1) review
      the importance of risk stratification before engaging in a particular strategy of
      care, (2) define the reperfusion strategies available, (3) review the specific
      agents (antiplatelet and anticoagulant) that support reperfusion strategies, and
      (4) apply the strategies of care in the context of the clinical presentation.

PMID- 29329797
TI  - Reducing Risk of Dementia in AF-Is Oral Anticoagulation the Key?

PMID- 29329799
TI  - Cardiac surgery combined with bypass from the ascending aorta to the bilateral
      femoral arteries for severe aorto-iliac occlusion: A case series.

PMID- 29329800
TI  - Surgery for extensive, chronic aortic dissection: What about the elephant
      (trunks) in the room?

PMID- 29329798
TI  - Efficacy of Warfarin Anticoagulation and Incident Dementia in a Community-Based
      Cohort of Atrial Fibrillation.
AB  - OBJECTIVE: To study the association between time in therapeutic range (TTR)
      during warfarin therapy and risk of dementia in a population-based cohort of
      incident atrial fibrillation (AF). PATIENTS AND METHODS: We conducted an
      observational population-based study of 2800 nondemented patients with incident
      AF from January 1, 2000, through December 31, 2010. The association of incident
      dementia with warfarin therapy and TTR was examined using Cox proportional
      hazards regression models. RESULTS: Mean patient age was 71.2 years; 53% were men
      (n=1495), and warfarin was prescribed to 50.5% (n=1414) within 90 days of AF
      diagnosis. Incident dementia diagnosis occurred in 357 patients (12.8%) over a
      mean +/- SD follow-up of 5.0+/-3.7 years. After adjusting for confounders,
      warfarin therapy was associated with a reduced incidence of dementia (hazard
      ratio [HR], 0.80; 95% CI, 0.64-0.99). However, only those in the 2 highest
      quartiles of TTR were associated with lower risk of dementia. A 10% increase in
      TTR with a 10% reduction in time spent in the subtherapeutic (HR, 0.71; 95% CI,
      0.64-0.79) and supratherapeutic (HR, 0.67; 95% CI, 0.57-0.79) ranges were
      associated with decreased risk of dementia. CONCLUSION: In the community,
      warfarin therapy for AF is associated with a 20% reduction in risk of dementia.
      Increasing TTR on warfarin is associated with reduced risk of dementia. The risk
      of dementia was reduced with a reduction in time spent in subtherapeutic and
      supratherapeutic international normalized ratio range. Effective anticoagulation
      may prevent cognitive impairment in patients with AF.

PMID- 29329801
TI  - More than just numbers: Counting thoracic aortic disease just isn't that simple.

PMID- 29329802
TI  - Can use of an administrative database improve accuracy of hospital-reported
      readmission rates?
AB  - OBJECTIVES: Readmission rates after cardiac surgery are being used as a quality
      indicator; they are also being collected by Medicare and are tied to
      reimbursement. Accurate knowledge of readmission rates may be difficult to
      achieve because patients may be readmitted to different hospitals. In our area,
      81 hospitals share administrative claims data; 28 of these hospitals (from 5
      different hospital systems) do cardiac surgery and share Society of Thoracic
      Surgeons (STS) clinical data. We used these 2 sources to compare the readmissions
      data for accuracy. METHODS: A total of 45,539 STS records from January 2008 to
      December 2016 were matched with the hospital billing data records. Using the
      index visit as the start date, the billing records were queried for any
      subsequent in-patient visits for that patient. The billing records included date
      of readmission and hospital of readmission data and were compared with the data
      captured in the STS record. RESULTS: We found 1153 (2.5%) patients who had STS
      records that were marked "No" or "missing," but there were billing records that
      showed a readmission. The reported STS readmission rate of 4796 (10.5%)
      underreported the readmission rate by 2.5 actual percentage points. The true rate
      should have been 13.0%. Actual readmission rate was 23.8% higher than reported by
      the clinical database. Approximately 36% of readmissions were to a hospital that
      was a part of a different hospital system. CONCLUSIONS: It is important to know
      accurate readmission rates for quality improvement processes and institutional
      financial planning. Matching patient records to an administrative database showed
      that the clinical database may fail to capture many readmissions. Combining data
      with an administrative database can enhance accuracy of reporting.

PMID- 29329803
TI  - Explant of a ball and cage valve 42 years after initial implant.

PMID- 29329804
TI  - A rapid and sensitive fluorometric method for determination of aldehyde oxidase
      activity.
AB  - Previous research has characterized the important role of aldehyde oxidases (AOX)
      in biotransformation of N-heterocyclic therapeutic drugs and environmental
      contaminants in mammals. Research pertaining to AOX activity in non-mammalian
      vertebrates, however, is scarce, despite its biological role as a potentially
      important metabolic pathway for xenobiotics. One of the limiting factors of
      research on AOX is that available photometric methods are relatively insensitive,
      limited in throughput, and prone to cross-reactivity from other enzymes.
      Therefore, this study aimed to develop a novel and improved fluorometric AOX
      assay. This assay is based on the conversion of the exogenous aldehyde substrate
      4-(dimethyl)amino cinnamaldehyde to its corresponding fluorescent acid by AOX,
      and was evaluated using partially purified hepatic cytosol from rat, human, and
      rainbow trout. Purification of native cytosol by heat treatment and ammonium
      sulfate precipitation resulted in increased specific activity of AOX. Michaelis
      Menten kinetic parameters (Kmand Vmax) were comparable to values previously
      generated by photometric methods. Furthermore, effects of the inhibitor
      hydralazine on AOX activity revealed half maximal inhibitory concentrations
      comparable to those generated using conventional methods. Product identity was
      confirmed by liquid chromatography and mass spectrometry. In summary, this study
      successfully developed a rapid and sensitive assay for determination of AOX
      activity in across different vertebrate species that is 4- to 10-fold more
      sensitive compared to conventional absorbance-based methods. It can be applied in
      environmental, toxicological, and pharmacological studies relating to
      identification of AOX substrates, as well as the induction of AOX expression
      through drugs and environmental contaminants.

PMID- 29329805
TI  - Preparative expression and purification of a nacreous protein N16 and testing its
      effect on osteoporosis rat model.
AB  - N16, a nacreous protein isolated from Pinctada martensii, is related to nacreous
      layer formation. Our previous study indicated that N16 showed dual regulatory
      effects by inducing osteoblast biomineralization as well as inhibiting osteoclast
      formation. In order to obtain large quantity of N16 for animal experiment and
      clinical trial, a fermentation and preparative purification method was
      established. The N16 cDNA was cloned to a BL21(DE3)plysE-pET32a vector and grown
      in a 20 L fermenter. The medium, temperature, pH and dissolved oxygen (DO) were
      optimized. N16 was expressed in inclusion bodies. It was denatured and refolded
      in 8 M urea buffer and purified to 97% purity by passing through a gel filtration
      column. The glucocorticoid induced osteoporosis (GIO) rat model was used to
      investigate the anti-osteoporosis activity of N16 in vivo. Results showed that
      the decrease of the bone mineral density (BMD) and the ultimate load was
      significantly relieved after N16 treatment. N16 displayed dual regulatory effects
      by promoting osteogenesis as well as inhibiting bone resorption in vivo. Our work
      will contribute to further clinical studies on N16 for osteoporosis treatment.

PMID- 29329806
TI  - Effect of different animal fat and plant oil additives on physicochemical,
      mechanical, antimicrobial and antioxidant properties of chitosan films.
AB  - Practical application of chitosan-essential oil blend films is limited due to the
      uneconomical extraction procedure of essential oils from plants. This study aimed
      to produce chitosan films blended with low cost and commercially available oils
      and fats consumed in daily human diet (olive, corn and sunflower oils, butter and
      animal fats). The study also focused on how physicochemical, biological and
      mechanical properties of chitosan blend films were influenced by the
      incorporation of oils and fats with varying unsaturation degrees. Possible
      interactions of chitosan film matrix with incorporated oils or fats were
      investigated. Chitosan-olive oil film showed better surface morphology and higher
      thermal stability than the films with other unsaturated oils. Tensile strength,
      Young's modulus and elongation at break were improved by 57.2%, 25.1% and 31.7%
      for chitosan-olive oil film, respectively. Chitosan-olive oil blend film had the
      highest antibacterial activity (almost equal to that of commercial antibiotic
      gentamicin). Edible films obtained from by incorporation of natural oils and fats
      into chitosan can help produce an environmentally friendly packaging material
      that is low cost and easily manufactured.

PMID- 29329807
TI  - Nasal adhesive patches - Approach for topical application for dry nasal syndrome.
AB  - This present study intended to provide nasal adhesive formulations for the
      topical treatment of dry nasal syndrome. Mucoadhesive films were prepared
      according to solvent evaporation method consisting of well-known polymers such as
      gellan and carboxymethyl cellulose. Mucoadhesive films (A-E) were evaluated in
      respect to their physicochemical properties, stability, disintegration behavior
      and tensile strength. Moreover, uptake capacity of adhesive films was
      investigated according to three assays vapor uptake/ permeability and water
      uptake. Mucoadhesive assessment was carried out on porcine nasal mucosa in terms
      of adhesion time, wash off resistance and spreadability. Obtained finings
      indicated 4.2 (B) > 2.55 (A) > 1.8 (D) > 1.3 (C) > 1(E) fold vapor uptake
      ranking. The bioadhesive results indicated a 60-fold (B) > 8.58-fold (C) > 7.42
      fold (E) > 1.3-fold (D) improvement in comparison to formulation A. A variety of
      humectants such as urea, Aloe vera, allantoin and hyaluronic acid was
      incorporated in the formulations. Taken together, nasal adhesive films convinced
      with their proficiency of mucoadhesiveness and stability to be suitable in the
      management of dry nasal syndrome.

PMID- 29329808
TI  - Structural and energetic basis for the molecular recognition of dual synthetic
      vs. natural inhibitors of EGFR/HER2.
AB  - Activation of EGFR starts by ligand binding at the extracellular domain which
      results in homo and heterodimerization, leading to phosphorylation, activation of
      downstream signaling pathways which upregulate expression of genes, proliferation
      and angiogenesis. Abnormalities in the expression of EGFR play a critical role in
      the development of different types of cancer. HER2 is the preferred
      heterodimerization partner for EGFR; this biological characteristic together with
      the high percentage of structural homology has been exploited in the design of
      dual synthetic inhibitors against EGFR/HER2. Herein we combined structural data
      and molecular dynamics (MD) simulations coupled to an MMGBSA approach to provide
      insight into the binding mechanism between two dual synthetics (lapatinib and TAK
      285) and one dual natural inhibitor (EGCG) which target EGFR/HER2. In addition,
      we proposed some EGCG derivatives which were filtered through in silico
      screening. Structural analysis demonstrated that the coupling of synthetic,
      natural or newly designed compounds impacts the conformational space of EGFR and
      HER2 differently. Energetic analysis points out that lapatinib and TAK-285 have
      better affinity for inactive EGFR than the active EGFR state or HER2, whereas
      some EGCG derivatives seem to form binding affinities similar to those observed
      for lapatinib or TAK-285.

PMID- 29329809
TI  - New N-guanidinium chitosan/silica ionic microhybrids as efficient adsorbent for
      dye removal from waste water.
AB  - N-guanidinium chitosan acetate, a new chitosan derivative, was prepared via
      direct guanylation reaction between chitosan and cyanamide in the presence of
      scandium (III) triflate. Treatment of N-guanidinium chitosan acetate with 3
      (trihydroxysilyl)-1-propanesulphonic acid followed by sol-gel reaction allowed
      accessing N-guanidinium chitosan silica hybrid material. The new ionic
      microhybrid was characterized using 13C and 29Si solid state NMR, IR
      spectroscopy, scanning electron microscopy and thermogravimetry. Further studies
      in the area of separation indicated very high adsorption capacity for cationic
      dyes such as methylene blue (MB), with capacities up to 935 mg/g. The adsorption
      kinetics can accurately be described by pseudo second-order model. Equilibrium
      adsorption data showed a better fit with Langmuir adsorption isotherm model.
      Recycling test showed that the ionic microhybrid can be reused in at least five
      adsorption-desorption cycles. These results open new perspectives and
      possibilities for the design of novel hybrid adsorbents for industrial and
      environmental applications.

PMID- 29329810
TI  - Facile microencapsulation of olive oil in porous starch granules: Fabrication,
      characterization, and oxidative stability.
AB  - In this study, starch with porous structures derived from purple sweet potato was
      prepared and used as a food-grade polymer for the microencapsulation of olive
      oil. The optimal reaction conditions for preparing porous starch were determined
      to improve its adsorption capacity as effective microcapsule-wall materials.
      Olive oil was then impregnated in microspheres, and loading ratio was optimized
      by investigating the restrictive factors, including the mass ratio of olive oil
      to porous starch, as well as the embedding temperature and time. The presence of
      olive oil in the starch matrix was confirmed by SEM, FTIR, and TGA. Results
      demonstrated that the porous starch-based microencapsulation exhibit a stable
      olive oil loading ratio and a significant improvement in oxidative stability
      compared with free olive oil. The newly-proposed process used in this work was
      easy to scale up for developing a new and attractive method for oil protection in
      the food industry.

PMID- 29329811
TI  - Cardioprotection activity and mechanism of Astragalus polysaccharide in vivo and
      in vitro.
AB  - Astragalus polysaccharides (ASP) is extracted from Astragalus, and is the main
      active ingredient of Astragalus membranaceus. The purpose of this study was to
      investigate the protective effect of ASP on rat cardiomyocytes damage induced by
      myocardial ischemia and reperfusion injury (MVRI) and isoprenaline(ISO) in vivo
      and in vitro. The model of cardiomyocytes damage was induced using MVRI in a rat
      in vivo and also using ISO in cell. After ASP intervention, the protective effect
      of ASP on cardiomyocytes was evaluated by animal experimental and cell
      experimental. The results show that ASP can relieve the increase of cell volume
      in myocardium, reduce the apoptosis of cell in myocardial tissue caused by MVRI
      in vivo. At the cellular level, ASP can reverse the decrease of cell activity
      induced by ISO, inhibit the apoptosis, and decrease the levels of intracellular
      reactive oxygen species. Mechanistically at the molecular level, these effects
      are elicited via down-regulation of the protein levels of caspase-3 and bax and
      up-regulation of the protein levels of bcl-2 in both in vivo and in vitro. These
      results demonstrate that ASP has a protective efficacy in MVRI/ISO-treated
      cardiomyocytes by inhibiting the apoptosis.

PMID- 29329812
TI  - Synergistic effect of polysaccharides, betalain pigment and phenolic compounds of
      red prickly pear (Opuntia stricta) in the stabilization of salami.
AB  - The aim of this work is to try to substitute some synthetic additives by a
      natural extract from red prickly pear (Opuntia stricta) which known by its
      richness on bioactive polysaccharides mainly consisting of galactose, rhamnose
      and galacturonic acid. This natural fruit has a high content of carbohydrates
      above 18.81% FM. It contains also a high level of polyphenols 152.25 +/- 0.26 MUg
      QE/mg PPE and flavonoids about 370.60 +/- 0.12 MUg GAE/mg of PPE. In addition,
      prickly pear extract (PPE) displayed a strong antioxidant and antimicrobial
      activities. These activities are likely due to its phenolic, flavonoid and
      carbohydrate contents. Moreover, the addition of 2.5% of PPE, as a natural
      colorant and antimicrobial agent in salami formulation, causes a decrease in
      hardness and chewiness of the formulated salami. Interestingly, PPE inhibited
      bacterial growth in salami stored at 4  degrees C over 30 days. Sensorial
      analysis shows that the color, taste and texture of salami prepared with 2.5% of
      PPE are markedly more appreciated by panelists. Our results suggest that the
      betalain pigment, carbohydrate and phenolic compounds present in PPE could be
      used as a natural colorant, antioxidant and antimicrobial agent without change of
      the sensory characteristics.

PMID- 29329814
TI  - Interaction between structurally different heteroexopolysaccharides and beta
      lactoglobulin studied by solution scattering and analytical ultracentrifugation.
AB  - Despite a very large number of bacterial exopolysaccharides have been reported,
      detailed knowledge on their molecular structures and associative interactions
      with proteins is lacking. Small-angle X-ray scattering, dynamic light scattering
      and analytical ultracentrifugation (AUC) were used to characterize the
      interactions of six lactic acid bacterial heteroexopolysaccharides (HePS-1-HePS
      6) with beta-lactoglobulin (BLG). Compared to free HePSs, a large increase in the
      X-ray radius of gyration RG, maximum length L and hydrodynamic diameter dH of
      HePS-1-HePS-4 mixed with BLG revealed strong aggregation, the extent of which
      depended on the compact conformation and degree of branching of these HePSs. No
      significant effects were observed with HePS-5 and HePS-6. Turbidity and AUC
      analyses showed that both soluble and insoluble BLG-HePS complexes were formed.
      The findings provide new insights into the role of molecular structures in
      associative interactions between HePSs and BLG which has relevance for various
      industrial applications.

PMID- 29329813
TI  - Effects of metal ions in tea polysaccharides on their in vitro antioxidant
      activity and hypoglycemic activity.
AB  - Total tea polysaccharides (TTPS) were extracted from two kinds of pruning leaves
      of tea plant and fractionated into neutral tea polysaccharides (TPSI) and acidic
      tea polysaccharides (TPSII) by anion exchange resin D315. Some physicochemical
      properties, including structure, monosaccharide composition, and molecular weight
      distribution, as well as the 4 in vitro antioxidant activities and inhibitory
      effects on alpha-glucosidase of above polysaccharides before and after removing
      metal ions were investigated. By comparing TTPS and TPSII, we found that they
      exhibited different antioxidant activities and inhibitory actions against alpha
      glucosidase after their metal ions were removed. However, the in vitro
      antioxidant activities and inhibitory effects on alpha-glucosidase of TPSI were
      substantially improved. The study can be a certain reference for tea and soil
      selection. At the same time, we suggested that pruning leaves of tea plant could
      be treated as a potential resource for the development of polysaccharide
      antioxidants and hypoglycemic products.

PMID- 29329815
TI  - Exploring molecular insights into the interaction mechanism of cholesterol
      derivatives with the Mce4A: A combined spectroscopic and molecular dynamic
      simulation studies.
AB  - Mammalian cell entry protein (Mce4A) is a member of MCE-family, and is being
      considered as a potential drug target of Mycobacterium tuberculosis infection
      because it is required for invasion and latent survival of pathogen by utilizing
      host's cholesterol. In the present study, we performed molecular docking followed
      by 100 ns MD simulation studies to understand the mechanism of interaction of
      Mce4A to the cholesterol derivatives and probucol. The selected ligands,
      cholesterol, 25-hydroxycholesterol, 5-cholesten-3beta-ol-7-one and probucol bind
      to the predicted active site cavity of Mce4A, and complexes remain stable during
      entire simulation of 100 ns. In silico studies were further validated by
      fluorescence-binding studies to calculate actual binding affinity and number of
      binding site(s). The non-toxicity of all ligands was confirmed on human monocytic
      cell (THP1) by MTT assay. This work provides a deeper insight into the mechanism
      of interaction of Mce4A to cholesterol derivatives, which may be further
      exploited to design potential and specific inhibitors to ameliorate the
      Mycobacterium pathogenesis.

PMID- 29329816
TI  - Structural polymorphism of a cytosine-rich DNA sequence forming i-motif
      structure: Exploring pH based biosensors.
AB  - Sequence recognition and conformational polymorphism enable DNA to emerge out as
      a substantial tool in fabricating the devices within nano-dimensions. These DNA
      associated nano devices work on the principle of conformational switches, which
      can be facilitated by many factors like sequence of DNA/RNA strand, change in pH
      or temperature, enzyme or ligand interactions etc. Thus, controlling these DNA
      conformational changes to acquire the desired function is significant for
      evolving DNA hybridization biosensor, used in genetic screening and molecular
      diagnosis. For exploring this conformational switching ability of cytosine-rich
      DNA oligonucleotides as a function of pH for their potential usage as biosensors,
      this study has been designed. A C-rich stretch of DNA sequence (5'
      TCCCCCAATTAATTCCCCCA-3'; SG20c) has been investigated using UV-Thermal
      denaturation, poly-acrylamide gel electrophoresis and CD spectroscopy. The SG20c
      sequence is shown to adopt various topologies of i-motif structure at low pH.
      This pH dependent transition of SG20c from unstructured single strand to
      unimolecular and bimolecular i-motif structures can further be exploited for its
      utilization as switching on/off pH-based biosensors.

PMID- 29329817
TI  - Isothermal chemical denaturation as a complementary tool to overcome limitations
      of thermal differential scanning fluorimetry in predicting physical stability of
      protein formulations.
AB  - Various stability indicating techniques find application in the early stage
      development of novel therapeutic protein candidates. Some of these techniques are
      used to select formulation conditions that provide high protein physical
      stability. Such approach is highly dependent on the reliability of the stability
      indicating technique used. In this work, we present a formulation case study in
      which we evaluate the ability of differential scanning fluorimetry (DSF) and
      isothermal chemical denaturation (ICD) to predict the physical stability of a
      model monoclonal antibody during accelerated stability studies. First, we show
      that a thermal denaturation technique like DSF can provide misleading physical
      stability rankings due to buffer specific pH shifts during heating. Next, we
      demonstrate how isothermal chemical denaturation can be used to tackle the above
      mentioned challenge. Subsequently, we show that the concentration dependence of
      the Gibbs free energy of unfolding determined by ICD provides better predictions
      for the protein physical stability in comparison to the often-used Tm (melting
      temperature of the protein determined with DSF) and Cm (concentration of
      denaturant needed to unfold 50% of the protein determined with ICD). Finally, we
      give a suggestion for a rational approach which includes a combination of DSF and
      ICD to obtain accurate and reliable protein physical stability ranking in
      different formulations.

PMID- 29329818
TI  - Hybrid Imaging in Ischemic Heart Disease.
AB  - Hybrid imaging for ischemic heart disease refers to the fusion of information
      from a single or usually from multiple cardiovascular imaging modalities enabling
      synergistic assessment of the presence, the extent, and the severity of coronary
      atherosclerotic disease along with the hemodynamic significance of lesions and/or
      with evaluation of the myocardial function. A combination of coronary computed
      tomography angiography with myocardial perfusion imaging, such as single-photon
      emission computed tomography and positron emission tomography, has been adopted
      in several centers and implemented in international coronary artery disease
      management guidelines. Interest has increased in novel hybrid methods including
      coronary computed tomography angiography-derived fractional flow reserve and
      computed tomography perfusion and these techniques hold promise for the imminent
      diagnostic and management approaches of patients with coronary artery disease. In
      this review, we discuss the currently available hybrid noninvasive imaging
      modalities used in clinical practice, research approaches, and exciting potential
      future technological developments.

PMID- 29329819
TI  - The effect of continuous positive airway pressure on spectral encephalogram
      characteristics in stroke patients with obstructive sleep apnea.
AB  - OBJECTIVES: To evaluate if treatment with continuous positive airway pressure
      (CPAP) compared to usual care in stroke patients with obstructive sleep apnea
      (OSA) over one month reduces delta and alpha oscillations on quantitative
      electroencephalography (EEG) in association with improvements in cognitive or
      functional outcomes. METHODS: Spectral EEG analysis was performed in patients
      with subacute stroke and OSA randomized to usual care or CPAP treatment from a
      previous study. RESULTS: A total of 23 subjects were included. Compared to CPAP
      (n = 14), those in the control (n = 9) group demonstrated a significant increase
      in alpha power (p = 0.042). There was no between group differences for delta,
      theta or beta power. No significant correlation was demonstrated between the
      change in alpha power and indices of OSA severity or sleepiness. The increase in
      alpha power did not correlate with improvements in outcomes. CONCLUSION: Contrary
      to expectations CPAP treatment of OSA did not significantly decrease alpha and
      delta oscillations in stroke subjects.

PMID- 29329820
TI  - Increased testicular estradiol during the neonatal interval reduces Sertoli cell
      numbers.
AB  - Previous studies have demonstrated that reducing endogenous testicular estradiol
      in neonatal boars would stimulate increased proliferation of Sertoli cells during
      the neonatal interval. The objective of this experiment was to determine if
      increasing testicular estradiol would have the opposite effect of reducing
      Sertoli cell numbers during the neonatal interval. Five littermate pairs of boars
      were evaluated with one littermate receiving a silastic implant containing
      estradiol and the second receiving only silastic at 1.5 weeks of age. Testes were
      recovered at 6.5 weeks of age and Sertoli cell numbers determined. Littermates
      treated with exogenous estradiol had approximately two-thirds as many Sertoli
      cells as their control littermates (P < 0.001). This is additional evidence for
      regulation of Sertoli cell numbers during the neonatal interval by intra
      testicular estradiol.

PMID- 29329821
TI  - Diminished activation of the right Inferior Parietal Lobule as a neural substrate
      of impaired cartoon-jokes comprehension in schizophrenia outpatients.

PMID- 29329822
TI  - Lymphoma following clozapine exposure: More information needed.

PMID- 29329823
TI  - Atypical presentation of CMV pneumonia in a heart transplant patient.

PMID- 29329824
TI  - Total hysterectomy as hematocolpos treatment following bone marrow transplant. A
      rare complication of chronic graft-versus-host disease.

PMID- 29329825
TI  - Effectiveness and Safety of Transcatheter Aortic Valve Implantation in Patients
      With Pure Aortic Regurgitation and Advanced Heart Failure.
AB  - Results of transcatheter aortic valve implantation (TAVI) for treatment of severe
      noncalcific isolated aortic regurgitation (AR) complicated by advanced heart
      failure or cardiogenic shock has been previously reported only in isolated case
      reports. Current self-expanding transcatheter aortic valves are designed to treat
      aortic valve stenosis, and have also been implanted in cases of severe AR due to
      degenerated bioprosthesis and in very few cases of native aortic valves. We
      report 13 consecutive inoperable patients with noncalcific, pure AR, and advanced
      heart failure treated with emergency percutaneous transfemoral implantation with
      self-expandable CoreValves at our institution between July 2012 and September
      2017. The immediate and long-term clinical outcome was prospectively assessed
      according to the Valve Academic Research Consortium-2 criteria for device success
      and safety. All but 3 patients had previous surgery of the aortic root, including
      2 implants of Heart Mate-II left ventricle assist device; none had surgical
      aortic bioprosthesis at the time of the TAVI. Valve implantation was successful
      in 12 of 13 patients (92%) and 1 patient required a second unplanned valve
      procedure within 18 hours. Oversizing the prosthesis by approximately 15% yielded
      better results with 1 valve. Two patients with left ventricle assist device died
      within 30 days of TAVI. All patients who survived to hospital discharge had none
      or just mild residual AR, improved their cardiac function, and survived at long
      term without recurrence of clinical events. In conclusion, implanting self
      expandable transcatheter valves in patients pure AR in this small study was safe
      and effective, and represented an important option for inoperable patients with
      noncalcific severe AR.

PMID- 29329826
TI  - Gender Differences in Presentation, Treatment, and In-Hospital Outcome of
      Patients Admitted With Heart Failure Complicated by Atrial Fibrillation (from the
      Get With the Guidelines-Heart Failure [GWTG-HF] Registry).
AB  - Almost 25% of patients with heart failure (HF) have coexisting atrial
      fibrillation (AF), the latter of which may increase morbidity and mortality.
      Despite the high prevalence of HF with concomitant AF, this subgroup of patients
      remains understudied. This study examines gender differences in presentation,
      treatment and in-hospital outcome of patients with HF and AF. The Get With the
      Guidelines-Heart Failure (GWTG-HF) database enrolled 6,496 patients with HF who
      presented to Cooper University Hospital from 2005 to 2012. Twenty-four percent
      (1,561 patients) had concomitant AF. Pearson chi-square tests and the Student T
      tests were used to compare patient characteristics by gender. Multivariate
      logistic regression was used to predict in-hospital mortality. Six hundred sixty
      nine (42.8%) patients with HF and AF were women. Women were older (p <0.001), had
      a higher ejection fraction (p <0.001), had systolic hypertension (p <0.001), and
      were more likely to have health insurance (p <0.001). Despite a higher CHADS2
      score in women (p = 0.007), there was no gender difference in percent of
      anticoagulation medications prescribed before admission. Women were less likely
      to present with dizziness, lightheadedness, or syncope, and were more likely to
      be compliant with medications and diet recommendations before admission. Despite
      differences in presentation, co-morbidities, and therapy, in-hospital mortality
      was similar between men and women. Decreased appetite or early satiety predicted
      in-hospital mortality in women, whereas age, chest pain on admission, and
      decreased appetite or early satiety predicted in-hospital mortality in men. In
      conclusion, women presenting with HF complicated by AF clinically differ from
      men, but despite these differences, both groups shared similar symptom
      presentation and in-hospital mortality rates.

PMID- 29329828
TI  - Frequency and Prognostic Significance of Acute Kidney Recovery in Patients Who
      Underwent Transcatheter Aortic Valve Implantation.
AB  - Acute kidney injury (AKI) after transcatheter aortic valve implantation (TAVI) is
      associated with increased mortality. As significant hemodynamic improvement may
      occur with relief of aortic stenosis, we hypothesized that TAVI patients may
      demonstrate the opposite phenomena: acute kidney recovery (AKR). We studied the
      incidence and predictors of AKR in post-TAVI patients. A total of 366 consecutive
      patients underwent TAVI (January 2012 to January 2017) at a single center. We
      defined AKR as a 25% improvement in glomerular filtration rate (GFR) at 48 hours
      after TAVI. AKI-creatinine (Cr) was defined as an increase in Cr of >=0.3 mg/dl
      at 48 hours. Patients were categorized in 3 groups: AKR (>=25% increase in GFR),
      unchanged GFR, and AKI-GFR (inverse definition of AKR, >=25% decrease in GFR).
      Multivariable logistic regression defined independent predictors of AKR. AKR
      occurred in 1/3 of patients. AKI-Cr occurred in 13% of patients, whereas AKI-GFR
      occurred similarly in 15%. AKR and AKI occurred most frequently in patients with
      chronic kidney disease (CKD: GFR <= 60 ml/min/1.73 m2). Independent predictors of
      AKR-GFR by multivariable analysis were male gender, lack of chronic beta-blocker
      utilization, and presence of CKD. Notably, left ventricular dysfunction and
      contrast volume were not predictive of AKR. Transfusion occurred less frequently
      among patients with AKR compared with patients with AKI-GFR (11% vs 26%, p =
      0.03). Death occurred in 0% of AKR patients versus 9.3% of AKI-GFR patients (p
      <0.01). In conclusion, this is the first report of AKR after TAVI. Patients with
      CKD, male gender, and lack of pre-TAVI beta blockade were more likely to
      demonstrate AKR.

PMID- 29329827
TI  - Effect of Serum Adiponectin Levels on the Association Between Childhood Body Mass
      Index and Adulthood Carotid Intima-Media Thickness.
AB  - Childhood obesity predicts adult cardiovascular risk. We hypothesized that the
      association between childhood body mass index (BMI) and adult carotid intima
      media thickness (CIMT) may be modified by levels of adiponectin, an adipocytokine
      that connects body fatness with cardiovascular risk. The study sample included
      1,052 adults (71% white and 29% black, 57% female) aged 23.8 to 43.5 years who
      were previously examined as children in the Bogalusa Heart Study cohort, with an
      average follow-up period of 26.5 (range 14.1 to 29.6) years. Childhood BMI, low
      density lipoprotein cholesterol, high-density lipoprotein cholesterol,
      triglycerides, and systolic blood pressure were standardized to age-specific z
      scores. General linear models were used for data analyses. Childhood BMI (p =
      0.034), low-density lipoprotein cholesterol (p <0.001), and systolic blood
      pressure (p = 0.005), along with adult adiponectin levels (p = 0.002) were
      associated with adult CIMT, adjusted for race, sex, adult age, and cigarette
      smoking. Further, adult adiponectin levels significantly modified the association
      between childhood BMI and adult CIMT (P for interaction = 0.0003) such that a
      significant association between childhood BMI and adult CIMT (p <0.0001) was only
      observed in those with adiponectin levels below the median. In conclusion, these
      results suggest that serum adiponectin levels modify the association between
      childhood obesity and adult atherosclerosis, which has implications for risk
      stratification and targeted intervention for obese children with low levels of
      adiponectin.

PMID- 29329829
TI  - Effectiveness and safety of foam sclerotherapy with 5% ethanolamine oleate in the
      treatment of low-flow venous malformations in the head and neck region: a case
      series.
AB  - The aim of this study was to evaluate the effectiveness and safety of 5%
      ethanolamine oleate (EO) foam in the treatment of low-flow venous malformations
      in the head and neck region. Seventeen consecutive patients (six male, 11 female)
      and 34 low-flow venous malformations were enrolled. The vascular anomalies ranged
      between 20mm and 80mm in size. The typical clinical indication was a swelling
      (88.2%) with a purple colour (85.3%); the most frequent location was the tongue
      (23.5%). Ethanolamine oleate foam was produced via the Tessari method and applied
      at 10mg per 1cm to the vascular anomalies. This process resulted in the highest
      clinical healing score in 64.7% of cases, and half of the patients reported a
      high level of satisfaction (score >9). In the majority of cases (88.2%), the
      patients reported that the pain immediately postoperative was mild or moderate.
      There were direct relationships between vascular anomaly size and the volume of
      EO applied, the number of sessions, and healing (P<0.05). No recurrence was
      observed during 6 months of follow-up. This case series showed the effectiveness
      and safety of 5% EO foam for the treatment of venous malformations in the head
      and neck region.

PMID- 29329830
TI  - Theoretical research in structure characteristics of different inhibitors and
      differences of binding modes with CBP bromodomain.
AB  - The CBP (CREB (cAMP responsive element binding protein) binding protein)
      bromodomain (BRD) could recognize and bind with acetyl K382 of human tumor
      suppressor protein p53 which the mutation of encoding gene might cause human
      cancers. CBP-BRD serves as a promising drug target for several disease pathways
      and a series of effective drug have been discovered. In this study, molecular
      dynamics (MD) simulations and molecular mechanics generalized born surface area
      (MM-GB/SA) approaches were performed to investigate the different binding modes
      between five inhibitors with CBP-BRD. Based on the energy and conformation
      analyses, a potent core fragment is chosen to act as the starting point for new
      inhibitor design by means of LUDI and rational drug design approaches. Then,
      T.E.S.T and molinspirition were applied to evaluate oral bioavailability and drug
      promiscuity of the new molecules. These results shed light on the idea for
      further inhibitor design.

PMID- 29329831
TI  - Physicochemical properties, nutritional value and techno-functional properties of
      goldenberry (Physalis peruviana) waste powder concise title: Composition of
      goldenberry juice waste.
AB  - Goldenberry waste powder, contained 5.87% moisture, 15.89% protein, 13.72% fat,
      3.52% ash, 16.74% dietary fiber and 61% carbohydrates. Potassium (560 mg/100 g)
      was the predominant element followed by sodium (170 mg/100 g) and phosphorus (130
      mg/100 g). Amino acid analysis gave high levels of cystine/methionine, histidine
      and tyrosine/phenylalanine. Goldenberry waste powder had good levels of the
      techno-functional properties including water absorption index, swelling index,
      foaming capacity and stability (3.38 g/g, 5.24 ml/g, 4.09 and 72.0%,
      respectively). Fatty acids profile showed that linoleic acid was the predominant
      fatty acid followed by oleic, palmitic and stearic acids. Iodine value (109.5
      g/100 g of oil), acid value (2.36 mg KOH/g of oil), saponification value (183.8
      mg KOH/g of oil), peroxide value (8.2 meq/kg of oil) and refractive index
      (1.4735) were comparable to those of soybean and sunflower oils. Goldenberry
      waste oil exhibited absorbance in the UV range at 100-400 nm.

PMID- 29329832
TI  - Effects of cluster thinning on vine photosynthesis, berry ripeness and flavonoid
      composition of Cabernet Sauvignon.
AB  - Cluster thinning is a common practice for regulating vine yield and grape
      quality. The effects of cluster thinning on vine photosynthesis, berry ripeness
      and flavonoid composition of V. vinifera L. Cabernet Sauvignon were evaluated
      during two seasons. Half of the clusters were removed at pea-size and veraison
      relative to two controls, respectively. Both cluster thinning treatments
      significantly increased pruning weight and decreased yield. No effects of cluster
      thinning on berry growth, ripeness and flavonol composition were observed. Early
      cluster thinning decreased the photosynthetic rate at pea-size, but the effect
      diminished at post-veraison. Early cluster thinning significantly promoted the
      biosynthesis of anthocyanins but decreased the proportion of 3'5'-hydroxylated
      and acylated anthocyanins at veraison. Late cluster thinning decreased the
      proportions of 3'5'-hydroxylated and acylated anthocyanins. Additionally, Cluster
      thinning showed inconsistent effects on flavan-3-ol composition over the two
      seasons.

PMID- 29329833
TI  - Effect of brewing time and temperature on antioxidant capacity and phenols of
      white tea: Relationship with sensory properties.
AB  - White tea is highly consumed due to its sensory properties and health benefits,
      although most scientific reports don't include the analysis of both properties.
      Therefore, the objective of the present study was to unravel the best brewing
      conditions for optimal extraction of the bioactive compounds and antioxidant
      capacity, while realising the best sensory properties. Infusions of eighty
      commercial teas (sold in bags or leaves) were obtained at different time
      temperature ratios, studying bioactive compounds (caffeine and individual
      catechins), antioxidant capacity and sensory analysis. Brewing at 98  degrees C
      for 7 min was the best condition to obtain a high content of antioxidant
      polyphenols and pleasant sensory properties. Those teas sold in bags give rise to
      tea brews with almost double antioxidant capacity. In conclusion, it is very
      important to link sensory and chemical data to obtain optimal sensorial quality
      and the highest healthy properties in white tea infusions.

PMID- 29329834
TI  - Heterospectral two-dimensional correlation analysis with near-infrared
      hyperspectral imaging for monitoring oxidative damage of pork myofibrils during
      frozen storage.
AB  - Near-infrared (NIR) spectra contain abundant data, heterospectral two-dimensional
      correlation (H2D-CS) analysis offers a good way to interpret these data. For the
      first time, H2D-CS was used to correlate the NIR hyperspectral imaging (HSI) data
      with mid-infrared spectra and to identify feature-related wavebands for
      developing models for monitoring the oxidative damage of pork myofibrils during
      frozen storage. The HSI images were acquired at frozen state without thawing and
      the oxidative damage of myofibrils was assessed by carbonyl content. Results
      showed that the simplified PLSR model based on H2D-CS identified feature
      wavebands obtained determination coefficient in prediction (R2P) of 0.896 and
      root mean square error in prediction (RMSEP) of 0.177 nmol/mg protein, which was
      better than the partial least square regression (PLSR) model based on full
      wavebands (R2P = 0.856, RMSEP = 0.209 nmol/mg protein). Therefore, H2D-CS was
      effective in selecting feature-related wavebands of NIR HSI.

PMID- 29329835
TI  - In depth chemical investigation of Glycyrrhiza triphylla Fisch roots guided by a
      preliminary HPLC-ESIMSn profiling.
AB  - Chemical investigations on Glycyrrhiza spp. have mostly been focused on G. glabra
      (typically cultivated in Europe, henceforth called European licorice), G.
      uralensis and G. inflata (known as Chinese licorice) with little information on
      the constituents of other Glycyrrhiza species. According to the growing interest
      in further Glycyrrhiza spp. to be used as sweeteners, the roots of G. triphylla
      have been investigated. The LC-ESI/LTQOrbitrap/MS profile of the methanolic
      extract of G. triphylla roots guided the isolation of 21 compounds, of which the
      structures were elucidated by 1D- and 2D-NMR experiments. Based on this approach,
      6 previously unreported compounds including two isoflavones 7,5'-dihydroxy-6,3'
      dimethoxy-isoflavone-7-O-beta-d-glucopyranoside (4) and 7,5'-dihydroxy-6,3'
      dimethoxy-isoflavone-7-O-(7,8-dihydro-p-hydroxycinnamoyl)-beta-d-glucopyranoside
      (7) and four saponins, named licoricesaponins M3 (13), N2 (14), O2 (16) and P2
      (18), have been characterized. It is to be noted that the accurate masses of some
      compounds here reported for the first time corresponded to those of compounds
      previously described in Glycyrrhiza spp. Thus an approach based only on MS
      analysis could be misleading; only isolation followed by NMR analysis allowed us
      to unambiguously assign the structures of these previously unreported compounds.

PMID- 29329836
TI  - Fermented Apulian table olives: Effect of selected microbial starters on
      polyphenols composition, antioxidant activities and bioaccessibility.
AB  - The effects of fermentation by autochthonous microbial starters on phenolics
      composition of Apulian table olives, Bella di Cerignola (BDC), Termite di Bitetto
      (TDB) and Cellina di Nardo (CEL) were studied, highlighting also the cultivars
      influence. In BDC with starter, polyphenols amount doubled compared with
      commercial sample, while in TDB and CEL, phenolics remain almost unchanged. The
      main phenolics were hydroxytyrosol, tyrosol, verbascoside and luteolin, followed
      by hydroxytyrosol-acetate detected in BDC and cyanidine-3-glucoside and quercetin
      in CEL. Scavenger capacity in both DPPH and CAA assays, assessed the highest
      antioxidant effect for CEL with starters (21.7 mg Trolox eq/g FW; 8.5 MUmol
      hydroxytyrosol eq/100 g FW). The polyphenols were highly in vitro bioaccessible
      (>60%), although modifications in their profile, probably for combined effect of
      environment and microorganisms, were noted. Finally, fermented table olives are
      excellent source of health promoting compounds, since hydroxytyrosol and tyrosol
      are almost 8 times more than in olive oil.

PMID- 29329837
TI  - The fate and enantioselective behavior of zoxamide during wine-making process.
AB  - The fate of zoxamide and its enantiomers were evaluated in detail during wine
      making process. The enantiomers of zoxamide were separated and determined by
      ultra-high-performance liquid chromatography coupled with tandem mass
      spectrometry (UHPLC-MS/MS) after each processing procedure including washing,
      peeling, fermentation and clarification. Significant enantioselectivity was
      observed in all three treatments with the half-lives of R-zoxamide and S-zoxamide
      estimated to be 45.6 and 52.9 h in Group A, 45.0 and 52.1 h in Group B, 56.8 and
      70.7 h in Group C, respectively. The results indicated that R-zoxamide degraded
      faster than S-zoxamide during the fermentation process. The processing factors
      (PFs) of each procedure were generally less than 1, and the PF of the overall
      process ranged from 0.019 to 0.051, which indicated that the whole process can
      reduce the zoxamide residue in red and white wine obviously. The results could
      help facilitate more accurate risk assessments of zoxamide during wine-making
      process.

PMID- 29329838
TI  - Effect of extraction methods on the chemical components and taste quality of
      green tea extract.
AB  - The physicochemical properties of tea extracts are significantly affected by the
      extraction method. The aim of this study was to compare the effects of static and
      dynamic extractions on the concentrations of chemical components and taste
      quality of green tea extracts. Our results show that extraction of chemical
      components using static extraction follows a pseudo-second-order reaction, while
      that of dynamic extraction follows a first-order reaction. The concentrations of
      the solids, polyphenols, and free amino acids in green tea extract prepared by
      dynamic extraction were much higher, although the overall yields were not
      significantly different between the two extraction methods. Green tea extracts
      obtained via dynamic extraction were of lower bitterness and astringency, as well
      and higher intensities of umami and overall acceptability. These results suggest
      that dynamic extraction is more suitable for the processing of green tea
      concentrate because of the higher concentration of green tea extract.

PMID- 29329839
TI  - Bioaccessibility and potential bioavailability of phenolic compounds from achenes
      as a new target for strawberry breeding programs.
AB  - Strawberry is a major natural source of bioactive compounds. Botanically,
      strawberry is an aggregate fruit consisting of a fleshy floral receptacle that
      bears a cluster of real dry fruits (achenes). Existing knowledge on the phenolic
      composition of achenes and its contribution to that of the whole fruit is
      limited. Also, the gastric and intestinal bioavailability of phenols is poorly
      known. In this work, a combination of spectrophotometric and HPLC-DAD methods was
      used to analyse the phenolic composition of whole fruits and achenes before and
      after in vitro digestion. Five different phenol families were identified. Also,
      achenes were found to contribute a sizeable fraction of phenolic acids and
      hydrolysable tannins in the whole fruit. Because the mere presence of phenolic
      compounds in a food matrix does not ensure their ready absorption and
      bioavailability, polyphenol potential bioavailability could be an effective
      selection criterion for strawberry breeding programs aimed at improving dietary
      healthiness.

PMID- 29329840
TI  - Determination of colistin in animal tissues, egg, milk, and feed by ultra-high
      performance liquid chromatography-tandem mass spectrometry.
AB  - A confirmatory method for the determination of colistin in animal tissues, egg,
      milk, and feed was developed and validated. Colistin A and colistin B were
      extracted from samples with the mixture of 10% trichloroacetic acid-acetonitrile
      and isolated with mixed-mode weak cation exchange cartridge. Analytes were
      separated from matrix components using ultra-high performance liquid
      chromatography, and detected with electrospray ionization on a triple quadrupole
      mass spectrometer. Mean recoveries ranged from 78.0% to 115.6% with intra-day and
      inter-day relative standard deviation lower than 8.4% and 12.4%, respectively.
      The quantitation limits for different matrices were between 5 and 30 MUg/kg,
      which was satisfactory for surveillance monitoring. The developed method was
      applied to the analysis of real samples collected from different provinces of
      China, and 19 out of 348 samples were found to be contaminated, with the highest
      concentration of approximately 12,000 MUg/kg colistin A and 10,000 MUg/kg
      colistin B in feed.

PMID- 29329841
TI  - Effects of radio frequency assisted blanching on polyphenol oxidase, weight loss,
      texture, color and microstructure of potato.
AB  - This paper is focused on the effects of radio frequency (RF) heating on the
      relative activity of polyphenol oxidase (PPO), weight loss, texture, color, and
      microstructure of potatoes. The results showed that pure mushroom PPO was almost
      completely inactivated at 80  degrees C by RF heating. The relative activity of
      potato PPO reduced to less than 10% with increasing temperature (25-85  degrees
      C). Enzyme extract showed the lowest PPO relative activity at 85  degrees C after
      RF treatment, followed by the potato cuboids and mashed potato, about 0.19 +/-
      0.017%, 3.24 +/- 0.19%, and 3.54 +/- 0.04%, respectively. Circular dichroism
      analysis indicated that RF heating changed the secondary structure of PPO, as
      alpha-helix content decreased. Both electrode gap and temperature had significant
      effect (P < .05) on weight loss, color, and texture of the potato cuboids.
      Microstructure analysis showed the changes of potato cell and starch during RF
      heating.

PMID- 29329842
TI  - Optimization of microwave assisted extraction of Morus nigra L. fruits maximizing
      tyrosinase inhibitory activity with isolation of bioactive constituents.
AB  - Morus nigra L. is a beneficial food due to rich phenolic components. While aiming
      higher yields for bioactive constituents, reduction in terms of raw material,
      solvent, time and energy gained more importance to provide a sustainable life for
      human and nature. Microwave assisted extraction (MAE) of Morus nigra fruits was
      optimized in order to elicit process parameters maximizing bioactive metabolites
      and tyrosinase inhibitory activity. Spectrophotometry and UPLC-DAD-ESI-MS/MS
      systems were utilized for quantitative analysis of total phenol, flavonoid and
      anthocyanin contents. Optimum conditions for MAE were determined as 500 W, 35%
      ethanol, 10 min yielding 12.63 mg/g cya-3-glu equiv. anthocyanin and IC50 value
      of 1.60 mg/ml for tyrosinase inhibitory activity. Microwave extracts prevailed
      better outcomes compared to conventional extraction methods (10.93 mg/g content
      with IC50 of 2.81 mg/ml). MAE could be considered as an advanced technique to
      obtain extracts from Morus nigra fruits with higher bioactive content and
      activity.

PMID- 29329843
TI  - Partial substitution of NaCl by KCl and addition of flavor enhancers on probiotic
      Prato cheese: A study covering manufacturing, ripening and storage time.
AB  - Cheese is a suitable matrix to deliver probiotic strains but it contains a high
      amount of sodium. The effect of partial substitution of NaCl by KCl and the
      addition of flavor enhancers (l-arginine, yeast and oregano extract) on probiotic
      Prato cheese was investigated after 1, 30, and 60 d of refrigerated storage
      (immediately after manufacturing, and during ripening and storage).
      Microbiological (lactic acid bacteria and probiotic Lactobacillus casei 01 counts
      and survival under gastrointestinal conditions), physicochemical (pH,
      proteolysis, fatty acids), bioactivity (antioxidant effect and angiotensin I
      converting enzyme inhibitory activity), rheological, and water mobility by means
      of time domain low-field nuclear magnetic resonance were investigated.
      Significant changes in probiotic survival were observed; however, the sodium
      reduction and the addition of flavor enhancers did not constitute an obstacle to
      L. casei 01 (>108 CFU/g) during storage. Slight changes were observed in
      proteolysis, bioactivity, water mobility, texture profile, and fatty acids of the
      cheeses as a function of the flavor enhancer added. The sodium reduction and the
      supplementation of Prato cheese with probiotic cultures may be an effective
      alternative to the production of a potentially functional cheese.

PMID- 29329844
TI  - Use of an isoelectric solubilization/precipitation process to modify the
      functional properties of PSE (pale, soft, exudative)-like chicken meat protein: A
      mechanistic approach.
AB  - The functionality of pale, soft, exudative (PSE)-like chicken protein was
      improved by isoelectric solubilization/precipitation (ISP) treatment. PSE-like
      chicken proteins were solubilized at an acidic pH 3.5 or an alkaline pH 11.0,
      followed by precipitating at pH 5.5 and 6.2. PSE-like meat paste was treated as
      control (CON). Precipitated at pH 6.2 led to a more elastic gel than at pH 5.5.
      Water distribution of ISP-isolated protein was affected by precipitation pH. More
      tryptophan residues exposed and -SH was partially oxidized to disulfide bond
      after ISP treatment, which led to large aggregates formation and higher viscosity
      of ISP isolated proteins than of CON. Absolute zeta potential of alkali-treated
      protein was higher than other counterparts, indicating stronger electric
      repulsion. ISP treatments could convert alpha-helix structure to relatively
      irregular structures. Overall, solubilizing at pH 11.0, combined with a
      precipitation pH 6.2 ISP treatment offers a potential for enhanced functionality
      of PSE-like chicken protein.

PMID- 29329845
TI  - Viscoelastic behaviour of masa from corn flours obtained by nixtamalization with
      different calcium sources.
AB  - The viscoelastic characteristics of nixtamalized corn masa were assessed by the
      dynamic oscillatory test. Masa samples were prepared with flours obtained by
      nixtamalization with different calcium sources: Ca(OH)2 (traditional), wood ashes
      (classic), CaCO3 (ecological), CaSO4 (ecological), CaCl2 (ecological), and
      Ca(C2H5COO)2 (ecological). A sample cooking without calcium source was used as
      control. Storage (G') and loss (G'') moduli were higher in masa from traditional
      and classic processes indicating a more elastic and viscous masa. Masa of flours
      from CaCl2 and Ca(C2H5COO)2 had the lowest values of G' and G''. Viscoelastic
      properties were explained in terms of the degree of starch gelatinization, the
      hydrolysis of pericarp and fibre content, the calcium-starch and calcium-zein
      interactions, as well as the presence of amylose-lipid complexes. Nixtamalization
      with Ca(OH)2 and wood ashes gave the best viscoelastic characteristics of masa.

PMID- 29329846
TI  - Nutritionally enriched 1,3-diacylglycerol-rich oil: Low calorie fat with
      hypolipidemic effects in rats.
AB  - An enzymatic process was developed for the preparation of a nutritionally
      enriched 1,3-diacylglycerol(DAG)-rich oil from a blend of refined sunflower and
      rice bran oils. The process involves hydrolysis of vegetable oil blend using
      Candida cylindracea followed by esterification with glycerol using Lipozyme RM1M.
      The resultant DAG-rich oil contains 84% of DAG (66% of 1,3-DAG, 18% of 1,2-DAG)
      and 16% of triacylglycerol (TAG) along with micro nutrients like gamma-oryzanol,
      tocotrienols, tocopherols and phytosterols. Nutritional studies of the DAG-rich
      oil were conducted in Wistar rats and compared with sunflower oil (SFO). The
      calorific value of the DAG-rich oil was estimated to be 6.45 Kcals/g as against
      9.25 Kcals/g for SFO. The serum and liver cholesterol and TAG levels in rats fed
      with 1,3-DAG-rich oil were found to be significantly reduced as compared to rats
      fed diet containing SFO. We conclude that 1,3-DAG-rich oil is a low calorie fat
      and exhibits hypolipidemic effects.

PMID- 29329847
TI  - Encapsulation of anthocyanins from bilberries - Effects on bioavailability and
      intestinal accessibility in humans.
AB  - Anthocyanins are flavonoids that have been suggested to provide beneficial health
      effects. The biological activity of anthocyanins is influenced by their
      pharmacokinetic properties, but anthocyanins are associated with limited
      bioavailability in humans. In the presented study, we investigated how the
      encapsulation of bilberry extract (BE), a source of anthocyanins, with either
      whey protein or citrus pectin influences the bioavailability and intestinal
      accessibility of anthocyanins in humans. We performed an intervention study that
      analyzed anthocyanins and their degradation products in the urine, plasma, and
      ileal effluent of healthy volunteers and ileostomists (subjects without an intact
      colon). We were able to show, that whey protein encapsulation modulated short
      term bioavailability and that citrus pectin encapsulation increased intestinal
      accessibility during passage through the small intestine and modulated the
      formation of the degradation product phloroglucinol aldehyde (PGAL) in human
      plasma.

PMID- 29329849
TI  - Thermal degradation of chloramphenicol in model solutions, spiked tissues and
      incurred samples.
AB  - This study investigated the thermal degradation of a veterinary drug,
      chloramphenicol, in model solutions (water), as well as in spiked and incurred
      mussel tissues to understand its fate in the food supply chain. Thermal
      degradation kinetics followed a first-order model in water (e.g. degradation
      rate: 0.0018-0.0025 min-1 at 100  degrees C). After 1 h at 100  degrees C, the
      percentage degradation in spiked tissues (28.1 +/- 7.1%) was significantly
      different (p < .05) from the values in water (14.2 +/- 1.6%) and incurred mussel
      tissues (19.0 +/- 4.1%). Using liquid chromatography coupled to high-resolution
      accurate mass tandem mass spectrometry, the resulting degradation products of
      chloramphenicol were identified in water, spiked and incurred tissues, and were
      all different. Therefore, although the use of water models and spiking food
      samples may provide some information, our data confirm that "incurred models"
      should be systematically implemented to provide reliable information about
      veterinary drug residue stability for food safety risk assessments.

PMID- 29329848
TI  - Utilization of mixed adsorbents to extend frying oil life cycle in poultry
      processing.
AB  - The effects were studied of two different adsorbent combinations (com I;
      bentonite: activated carbon: celite = 3:4:1 and com II; bentonite: activated
      clay: celite = 3:4:1 + 1% citric acid) on the physico-chemical changes of oil
      used continuously for deep-fat frying of chicken drumsticks. The results showed
      that the % FFA was reduced by 44.3, PV by 50.2, and FOS reading by 40.1% in com I
      whereas reductions of 41.6, 44.9, and 32.8%, respectively, were found in com II.
      The oil treated with com II exhibited a lighter color than with com I. The
      changes of oil color in com I were L* 30.7, a* 1.7, and b* 31.9%; in com II they
      were 53.2, 19.1, and 39.5% respectively. The higher the L* observed, the better
      the oil quality obtained because of the bleaching ability of adsorbents.
      Therefore, the use of such adsorbents is recommended for poultry processing.

PMID- 29329850
TI  - GC-MS profiling, descriptive sensory analysis, and consumer acceptance of Costa
      Rican papaya (Carica papaya L.) fruit purees.
AB  - Volatiles of papaya purees from four Costa Rican cultivars were analysed by solid
      phase microextraction and gas chromatography-mass spectrometry. A total of 83
      volatiles was assigned in the purees, of which 19 were detected for the first
      time as papaya constituents. As revealed by multivariate statistics, i.e.,
      principal component analysis (PCA) and partial least squares discriminant
      analysis (PLS-DA), the purees may be allocated to terpene- and lactone-rich ('SH
      5'), ester-containing ('Criolla'), and intermediate chemotypes ('Pococi' and
      'Silvestre'). Descriptive sensory analysis and a consumer acceptance test were
      additionally performed. Floral, fruity, and honey-like notes were perceived at
      significantly higher intensities in 'SH-5' puree. The latter descriptors strongly
      correlated with volatiles discriminating 'SH-5' in the PCA and PLS-DA,
      respectively. Consumer acceptance of the papaya purees differed significantly.
      'Pococi' and 'SH-5' purees appear to be suitable for improving the nutritional
      value of blended fruit juices without impairing their sensory quality.

PMID- 29329851
TI  - Chemical characterization of Myrciaria floribunda (H. West ex Willd) fruit.
AB  - M. floribunda fruit was studied to characterize its chemical composition. The
      chemical composition, bioactive compounds, antioxidant activity and volatiles of
      the fruit were determined. The chemical composition was determined according to
      AOAC and AOCS, the bioactive compounds by HPLC, the volatiles by GCMS and the
      antioxidant activity by ABTS+ and DPPH methods. The chemical composition of the
      freeze-dried fruit was 1.89 g.100 g-1, 2.43 g.100 g-1, 4.78 g.100 g-1 and 90.89
      g.100 g-1 of ashes, lipids, proteins and total carbohydrates on a dry base,
      respectively. The concentration of the carotenoids was 52.22 mg.100 g-1 and for
      the flavonoid rutin was 78.56 mg.100 g-1. The gallic and ellagic acid contents
      were 5.45 mg.g-1 and 2.21 mg.g-1, respectively. The cis-beta-ocimene corresponded
      to 50.90% of the volatiles. The antioxidant activity by ABTS+ method was 550.14
      umol Trolox.g-1 and by the DPPH method the EC50 was 85.68 g.g-1. The fruits
      presented relevant antioxidant activity, a high concentration of carotenoids and
      of rutin.

PMID- 29329852
TI  - An integrated in silico/in vitro approach to assess the xenoestrogenic potential
      of Alternaria mycotoxins and metabolites.
AB  - Xenoestrogenic mycotoxins may contaminate food and feed posing a public health
      issue. Besides the zearalenone group, the Alternaria toxin alternariol (AOH) has
      been described as a potential mycoestrogen. However, the estrogenicity of
      Alternaria toxins is still largely overlooked and further data are needed to
      better describe the group toxicity. In the frame of risk assessment, mixed in
      silico/in vitro approaches already proved to be effective first-line analytical
      tools. An integrated in silico/in vitro approach was used to investigate the
      effects of metabolic and chemical modifications on the estrogenicity of AOH.
      Among the considered modifications, methylation was found critical for enhancing
      estrogenicity (as seen for alternariol monomethyl ether (AME)) while
      hydroxylation and glucuronidation had the opposite effect (as seen for 4-hydroxy
      AOH and 4-hydroxy AME). The structure-activity relationship analysis provided the
      structural rationale. Our results provide insights to design more efficient risk
      assessment studies expanding knowledge over the group toxicity.

PMID- 29329853
TI  - pH-controlled fermentation in mild alkaline conditions enhances bioactive
      compounds and functional features of lentil to ameliorate metabolic disturbances.
AB  - Lentil fermentation has a promising potential as a strategy for development of
      multifunctional ingredients targeting metabolic syndrome (MetS). Response surface
      methodology was applied to optimize lentil fermentation and study its effects on
      generation of peptides, soluble phenolics and bioactivities. Fermentation using
      Lactobacillus plantarum and Savinase(r) 16 L was carried out at different pH (6.5
      8.5) and times (5.5-30 h). Analysis of variance was performed to evaluate linear,
      quadratic and interaction effects between fermentation parameters. pH positively
      affected peptides, soluble phenolic compounds and antioxidant activity whereas a
      negative impact on lipase inhibitory activity was observed (p < .0001). Time
      showed positive effect on proteolysis and negatively affected angiotensin I
      converting enzyme inhibitory activity of fermented lentil (p < .0001).
      Multivariate optimization led to high levels of peptides, soluble phenolics and
      bioactivity of fermented lentil at pH 8.5 and 11.6 h. In conclusion, this study
      might contribute to the development of functional ingredients from lentil for
      MetS management.

PMID- 29329854
TI  - Enzymatic preparation of "functional oil" rich in feruloylated structured lipids
      with solvent-free ultrasound pretreatment.
AB  - In this study, a series of functional oils rich in feruloylated structured lipids
      (FSLs) was prepared by enzymatic transesterification of ethyl ferulate (EF) with
      triglycerides under ultrasound pretreatment. A conversion of more than 92.7% and
      controllable FSLs (3.1%-26.3%) can be obtained under the following conditions:
      16% enzyme, substrate ratio 1:5 (oil/EF, mol/mol), 85  degrees C, ultrasound 1 h,
      pulse mode 3 s/3s (working/waiting), and 17.0 W/mL. Compared to conventional
      mechanical stirring, the activation energy decreased from 50.0 kJ/mol to 40.7
      kJ/mol. The apparent kinetic constant increased by more than 13 times, and the
      time required for the maximum conversion reduced sharply from 20-60 h to 4-6h,
      which was the fastest rate for enzymatic synthesis of FSLs. The antioxidant
      activities of the functional oil significantly increased 1.0- to 8.1-fold more
      than that of the raw oil. The functional oil could be widely applied in various
      fields of functional foods.

PMID- 29329855
TI  - Production of three types of krill oils from krill meal by a three-step solvent
      extraction procedure.
AB  - In this study, a three-step extraction method (separately use acetone, hexane,
      and ethanol as extraction solvent in each step) was conducted to selectively
      extract three types of krill oils with different compositions. The lipid yields
      were 5.08% in step 1, 4.80% in step 2, and 9.11% in step 3, with a total of
      18.99%. The krill oil extracted with acetone in step 1 (A-KO) contained the
      lowest contents of phospholipids (PL) (2.32%) and n-3 polyunsaturated fatty acids
      (PUFA) (16.63%), but the highest levels of minor components (505.00 mg/kg of
      astaxanthin, 29.39 mg/100 g of tocopherols, 34.32 mg/100 g of vitamin A and 27.95
      mg/g of cholesterol). By contrast, despite having traces of minor components, the
      krill oil extracted using ethanol in step 3 (E-KO) was the most abundant in PL
      (59.52%) and n-3 PUFA (41.74%). The krill oil extracted using hexane in step 2 (H
      KO) expressed medium contents of all the testing indices. The oils showed
      significant differences in the antioxidant capacity (E-KO > H-KO > A-KO) which
      exhibited positive correlation with the PL content. These results could be used
      for further development of a wide range of krill oil products with tailor-made
      functions.

PMID- 29329856
TI  - Effect of tyrosinase-aided crosslinking on the IgE binding potential and
      conformational structure of shrimp (Metapenaeus ensis) tropomyosin.
AB  - The present study was performed to determine crosslinking and oxidative reactions
      catalyzed by tyrosinase (Tyr), caffeic acid (CA) and their combination with
      respect to IgE binding potential and conformational structure of shrimp
      tropomyosin (TM). Cross-links and IgE binding potentials were analyzed by SDS
      PAGE, western blot and indirect ELISA. While structural changes were
      characterized using surface hydrophobicity, ultraviolet (UV), fluorescence and
      circular dichroism (CD) spectroscopies. Maximum reduction in the IgG (37.19%) and
      IgE binding potentials (49.41%) were observed when treated with 2000 nkat/g Tyr +
      CA, as indicated by ELISA analyses. These findings correlated well with the
      denaturation of protein, as evident by slight blue shift and alterations in the
      ellipticities observed via structural analyses. The results demonstrated that
      addition of CA mediator with Tyr pronouncedly enhanced crosslinking, and altered
      the conformational structure, thereby mitigated allergenicity of TM, thus showing
      promise in developing novel food structures with reduced allergenic potential.

PMID- 29329857
TI  - Meat species identification using DNA-luminol interaction and their slow
      diffusion onto the biochip surface.
AB  - Recently, there has been a growing concern of consumers on the authenticity of
      food ingredients including adulteration with porcine and/or its derivatives.
      Therefore, this work reports on the development of a novel, simple, sensitive and
      rapid luminol-based electrochemiluminescence (ECL) technique for Sus scrofa
      (Porcine) DNA detection. Porcine DNA was firstly amplified using loop-mediated
      isothermal amplification (LAMP) method and subsequently added to luminol solution
      for further ECL analysis for quantification. The DNA-luminol complexes were
      formed causing the diffusion of luminol towards the electrode surface to be
      slowed down and hindered that resulted in low luminol intensity. The LAMP-ECL
      sensor is shown to be highly specific, sensitive (>=0.1 pg/MUL) and rapid (~5 min
      for detection). Hence, by employing this principle with carbon screen-printed
      electrode (SPE), this technique has a potential to be developed further into a
      compact biosensor for the verifying food authenticity.

PMID- 29329858
TI  - Mechanical wheat flour modification and its effect on protein network structure
      and dough rheology.
AB  - Mechanical flour modification is frequently associated with a reduced bread
      volume due to changed structural and functional properties of protein and starch.
      To clarify the effect of mechanical flour treatment on the protein network
      formation at the optimum kneading time (Peaktime), dough was produced with
      various mechanical starch modification (MSM) levels and visualized by confocal
      laser scanning microscope before being characterized by protein network analysis
      (PNA). Dough produced with high MSM showed a reduced branching rate (-14%), a
      high end-point rate (+25%) and an increased lacunarity (+139%), indicating a poor
      network connectivity with network interruptions. Alterations of the protein
      microstructure were closely related to the rheological dough properties. In this
      regard, reduced extensibility and resistance to extension of dough produced with
      high MSM levels were responsible for decreased dough height (Hm) during
      fermentation and thus might be the cause for lower baking volume of bread
      produced with high MSM.

PMID- 29329859
TI  - Effect of high pressure on structural modifications and enzymatic activity of a
      purified X-prolyl dipeptidyl aminopeptidase from Streptococcus thermophilus.
AB  - PepX aminopeptidase from Streptococcus thermophilus ACA DC 0022, used in Greek
      Feta cheese manufacturing, was purified. PepX comprises two subunits of equal
      molecular mass estimated, using SDS-PAGE and native-PAGE electrophoresis, to be
      86 kDa. The effects of high pressure processing (100-450 MPa, combined with 20-40
      degrees C) on purified PepX activity and structure were studied. Activation of
      the enzyme was observed after processing at 100-200 MPa and 20-30  degrees C.
      More intense processing conditions led to enzyme inactivation. PepX HP-induced
      conformational changes were also investigated through application of Circular
      Dichroism spectroscopy (CD). Pressures up to 200 MPa resulted in a structurally
      molten globule-like state where PepX maintained its secondary structure but the
      tertiary structure was substantially affected and enzyme activity increased. Both
      secondary and tertiary structures were affected severely by higher pressures (450
      MPa), which reduced enzyme activity.

PMID- 29329860
TI  - Ethyl carbamate: An emerging food and environmental toxicant.
AB  - Ethyl carbamate (EC), a chemical substance widely present in fermented food
      products and alcoholic beverages, has been classified as a Group 2A carcinogen by
      the International Agency for Research on Cancer (IARC). New evidence indicates
      that long-term exposure to EC may cause neurological disorders. Formation of EC
      in food and its metabolism have therefore been studied extensively and analytical
      methods for EC in various food matrices have been established. Due to the
      potential threat of EC to human health, mitigation strategies for EC in food
      products by physical, chemical, enzymatic, and genetic engineering methods have
      been developed. Natural products are suggested to provide protection against EC
      induced toxicity through the modulation of oxidative stress. This review
      summarizes knowledge on the formation and metabolism of EC, detection of EC in
      food products, toxic effects of EC on various organs, and mitigation strategies
      including prevention of EC-induced tumorigenesis and genotoxicity by natural
      products.

PMID- 29329861
TI  - In situ characterization of acidic and thermal protein denaturation by infrared
      microspectroscopy.
AB  - Foods meet acid pH during gastric digestion after cooking. An in situ infrared
      microspectroscopy approach was developed to detect the effects of heat and acid
      treatments on protein structure separately. Infrared spectra were obtained from
      meat samples treated with heat and/or acid, and wavenumbers accounting
      independently for the treatments were extracted by principal component
      regression. Extreme-acid treatment (pHinitial 2.0) was well predicted (0.5%
      error) by a simple ratio of as-observed spectral intensities at 1211 and 1396 cm
      1, reflecting a perturbation in the vibration of amino acid residues
      (phenylalanine, tyrosine and aspartic acid) by protein unfolding and protonation.
      Using the imaging mode of an IR microscope, meat protein acidification was
      evidenced with high spatial resolution. The heat effect was well discriminated
      from the acid effect by the ratio of as-observed intensities at 1666 and 1697 cm
      1 (0.9% error), indicating content of aggregated beta-sheets relative to alpha
      helix structure.

PMID- 29329862
TI  - Active compounds, antioxidant activity and alpha-glucosidase inhibitory activity
      of different varieties of Chaenomeles fruits.
AB  - Chaenomeles is an important source for food industry in China, and its planting
      area is expanding year by year. This study was conducted to evaluate different
      varieties of Chaenomeles by comparing the chemical compositions, antioxidant
      activity and alpha-glucosidase inhibitory activity of peels and fleshes from
      twelve varieties of Chaenomeles. In the results, peels of Chaenomeles contain
      more phenolics, flavonoids and triterpenes, and show better antioxidant activity
      and alpha-glucosidase inhibitory activity than their fleshes. All varieties of
      Chaenomeles perform different depend on cultivar and climatic conditions.
      Oleanolic acid, ursolic acid, protocatechuic acid, rutin, catechin, caffeic acid,
      syringic acid, epicatechin, hyperin, quercetin, kaempferol and chlorogenic acid
      are main active compounds in Chaenomeles. Zheng'an, Liufu, Zimugua1, Qijiang and
      Changjun get Top five scores. This is the first study on the peels and fleshes of
      twelve varieties of Chaenomeles, and it gives insights into variety selection in
      the planting and production of Chaenomeles.

PMID- 29329863
TI  - Preparation of gentiooligosaccharides using Trichoderma viride beta-glucosidase.
AB  - The recombinant plasmid pPIC9K-bgl1 containing beta-glucosidase bgl1 from
      Trichoderma viride was constructed by overlapping PCR and integrated into Pichia
      pastoris KM71. In order to assist the formation of disulfide bonds and thus
      improve protein folding efficiency, protein disulfide isomerase pdi was co
      expressed in the P. pastoris KM71/pPIC9K-bgl1/pPICZ-A-pdi strain, and
      fermentation in flasks resulted in enzyme activity of 143 U/ml. The enzyme
      activity of beta-glucosidase reached 1402 U/ml following optimisation of
      fermentation conditions in a 3.6 l bioreactor. With 80% glucose as substrate,
      gentiooligosaccharides were synthesised by beta-glucosidase-based reverse
      hydrolysis. A yield of 130 g/l was achieved with a conversion rate of 16.25%.
      With 20% glucose and 40% cellobiose as substrates, gentiooligosaccharides were
      synthesised by transglycosylation with a yield of 116 g/l and a conversion rate
      of 19.4%.

PMID- 29329864
TI  - Antioxidant and anti-freezing peptides from salmon collagen hydrolysate prepared
      by bacterial extracellular protease.
AB  - Extracted salmon skin collagen was hydrolysed with the free or immobilized
      extracellular protease of Vibrio sp. SQS2-3. The hydrolysate exhibited anti
      freezing activity (>3 kDa) and antioxidant activity (<3000 Da) after
      ultrafiltration. The antioxidant peptide was further purified by size-exclusion
      chromatography and found to scavenge DPPH (73.29 +/- 1.03%), OH (72.73 +/-
      3.34%,), and intracellular ROS in HUVECs; protect DNA against oxidation-induced
      damage; and have an ORAC of 2.78 +/- 0.28 mmol TE/g. The antioxidant peptide
      fraction was identified using mass spectrometry, and nineteen salmon collagen
      sourced peptides were obtained. Of these, the peptide Pro-Met-Arg-Gly-Gly-Gly-Gly
      Tyr-His-Tyr is a novel sequence and was the major component; this peptide was
      shown to have antioxidant activity via the ORAC assay (2.51 +/- 0.14 mmol TE/g).
      These results suggested that the protease from Vibrio sp. SQS2-3 is suitable for
      preparation of anti-freezing peptides and antioxidant peptides in a single step
      and represents a comprehensive use of fish skin collagen.

PMID- 29329865
TI  - In vitro evaluation of dietary compounds to reduce mercury bioavailability.
AB  - Mercury in foods, in inorganic form [Hg(II)] or as methylmercury (CH3Hg), can
      have adverse effects. Its elimination from foods is not technologically viable.
      To reduce human exposure, possible alternatives might be based on reducing its
      intestinal absorption. This study evaluates the ability of 23 dietary components
      to reduce the amount of mercury that is absorbed and reaches the bloodstream
      (bioavailability). We determined their effect on uptake of mercury in Caco-2
      cells, a model of intestinal epithelium, exposed to Hg(II) and CH3Hg standards
      and to swordfish bioaccessible fractions. Cysteine, homocysteine, glutathione,
      quercetin, albumin and tannic reduce bioavailability of both mercury species.
      Fe(II), lipoic acid, pectin, epigallocatechin and thiamine are also effective for
      Hg(II). Some of these strategies also reduce Hg bioavailability in swordfish
      (glutathione, cysteine, homocysteine). Moreover, extracts and supplements rich in
      these compounds are also effective. This knowledge may help to define dietary
      strategies to reduce in vivo mercury bioavailability.

PMID- 29329866
TI  - Corrigendum to "Effects of chemical composition and baking on in vitro
      digestibility of proteins in breads made from selected gluten-containing and
      gluten-free flours" [Food Chem. 233 (2017) 514-524].

PMID- 29329867
TI  - Corrigendum to "Characterization and screening of pyrrolizidine alkaloids and N
      oxides from botanicals and dietary supplements using UHPLC-high resolution mass
      spectrometry" [Food Chem. 178 (2015) 136-148].

PMID- 29329868
TI  - A procedure for the measurement of Oxygen Consumption Rates (OCRs) in red wines
      and some observations about the influence of wine initial chemical composition.
AB  - The rates at which wine consumes oxygen are important technological parameters
      for whose measurement there are not accepted procedures. In this work, volumes of
      8 wines are contacted with controlled volumes of air in air-tight tubes
      containing oxygen-sensors and are further agitated at 25  degrees C until O2
      consumption is complete. Three exposure levels of O2 were used: low (10 mg/L) and
      medium or high (18 or 32 mg/L plus the required amount to oxidize all wine SO2).
      In each oxygen level, 2-4 independent segments following pseudo-first order
      kinetics were identified, plus an initial segment at which wine consumed O2 very
      fast. Overall, multivariate data techniques identify six different Oxygen
      Consumption-Rates (OCRs) as required to completely define wine O2 consumption.
      Except the last one, all could be modeled from the wine initial chemical
      composition. Total acetaldehyde, Mn, Cu/Fe, blue and red pigments and gallic acid
      seem to be essential to determine these OCRs.

PMID- 29329869
TI  - A new equation for converting the parameter EC50 into the total antioxidant
      capacity TEAC and vice versa.
AB  - A new equation for converting EC50 into TEAC values and TEAC into EC50 is
      presented in this paper. The model was fitted to 180 data points of electron
      paramagnetic resonance (EPR) spectroscopy measurements of various food products.
      The model was tested basing on 75 EPR spectroscopy measurements. Moreover, the
      equation was tested on literature data. The determination coefficient between
      EC50cal and EC50exp was found to be R2 = 0.9762, while the determination
      coefficient between TEACcal and TEACexp was found to be R2 = 0.9686. Based on
      obtained results it can be concluded that the proposed model for converting EC50
      into TEAC values and TEAC into EC50 values works properly. This will enable a
      comparison of the antioxidant properties of products identified in literature
      through the use of different parameters (TEAC, EC50).

PMID- 29329870
TI  - 16-O-methylcafestol is present in ground roast Arabica coffees: Implications for
      authenticity testing.
AB  - High-field and low-field proton NMR spectroscopy were used to analyse lipophilic
      extracts from ground roast coffees. Using a sample preparation method that
      produced concentrated extracts, a small marker peak at 3.16 ppm was observed in
      30 Arabica coffees of assured origin. This signal has previously been believed
      absent from Arabicas, and has been used as a marker for detecting adulteration
      with robusta. Via 2D 600 MHz NMR and LC-MS, 16-O-methylcafestol and 16-O
      methylkahweol were detected for the first time in Arabica roast coffee and shown
      to be responsible for the marker peak. Using low-field NMR, robusta in Arabica
      could be detected at levels of the order of 1-2% w/w. A surveillance study of
      retail purchased "100% Arabica" coffees found that 6 out of 60 samples displayed
      the 3.16 ppm marker signal to a degree commensurate with adulteration at levels
      of 3-30% w/w.

PMID- 29329871
TI  - Isolation of proanthocyanidins from red wine, and their inhibitory effects on
      melanin synthesis in vitro.
AB  - The red wines made from Vitis vinifera were identified as skin-whitening
      effectors by using in vitro assays. OPCs in the wine were evaluated for
      tyrosinase activity and melanogenesis. Strong tyrosinase inhibitory activity was
      observed in fractions with high oligomeric proanthocyanidin (OPC) content. Among
      OPC dimers, a strong inhibitory effect on tyrosinase was observed with OPCs which
      contain (+)-catechin as an upper unit. Melanogenesis inhibitory effect was
      observed with OPCs which have (-)-epicatechin as upper units. Also, OPC trimers,
      upper and middle units joined with 4 -> 8 bonds, showed stronger effects compared
      to trimers with 4 -> 6 linkages. Interestingly, (-)-epicatechin-(4beta -> 8)-(-)
      epicatechin 3-O-gallate, which is a unique component of grapes has potent
      inhibitory effects on both tyrosinase and melanogenesis. Our data provide
      structural information about such active compounds. These results suggest that
      red wines containing OPC, have high melanogenesis inhibitory effect and are
      supposed to have skin-whitening effect.

PMID- 29329872
TI  - Development and validation of a HILIC-UV method for the determination of
      nucleotides in fish samples.
AB  - The aim of this work was the development of a simple, novel and accurate method
      for the determination of adenosine triphosphate (ATP) and its first five
      catabolites: adenosine diphosphate (ADP), adenosine monophosphate (AMP), inosine
      monophosphate (IMP), inosine (Ino) and hypoxanthine (Hx), in fish tissue, based
      on hydrophilic interaction liquid chromatography (HILIC). For this purpose, a
      stationary phase for polar and hydrophilic compounds (ZIC-pHILIC) was used. The
      effect of different chromatographic parameters and the molecular mechanism based
      on the van't Hoff plot were examined. The t-test and Dixon's Q-test were applied
      in order to examine statistical differences and outlier values. The recovery of
      the method ranged between 82.7% and 127% and the %RSD values were lower than 10%
      for all analytes determined. The method was applied in frozen sea bream samples
      stored at 0-4  degrees C. The Ki-, G-, H- and F values were calculated for the
      estimation of the level of fish freshness.

PMID- 29329873
TI  - Preparation and characterization of citral-loaded solid lipid nanoparticles.
AB  - Citral-loaded solid lipid nanoparticles (citral-SLNs) were prepared via a high
      pressure homogenization method, using glyceryl monostearate (GMS) as the solid
      lipid and a mixture of Tween 80 (T-80) and Span 80 (S-80) at a weight ratio of
      1:1 as the surfactant. The microstructure and properties of the citral-SLNs were
      characterized by dynamic light scattering (DLS), scanning electron microscopy
      (SEM), differential scanning calorimetry (DSC), Fourier-transform infrared
      spectroscopy (FTIR), X-ray diffraction (XRD) and thermal gravimetric analysis
      (TGA). The chemical stability of citral in the citral-SLNs was analyzed by solid
      phase microextraction gas chromatography (SPME-GC). The GC results showed that
      67.0% of the citral remained in the citral-SLN suspensions after 12 days, while
      only 8.22% remained in the control. Therefore, the encapsulation of citral in the
      solid lipid can enhance its stability in acidic surroundings.

PMID- 29329874
TI  - A survey of free glutamic acid in foods using a robust LC-MS/MS method.
AB  - An effective and simultaneous liquid chromatography-tandem mass spectrometry (LC
      MS/MS) method was used with the aim of quantifying monosodium glutamate (MSG) in
      foodstuffs, such as chips, taste cubes, sauces and soups. The results were linear
      (R2 = 1), with very low LOD and LOQ values, 1.0 ug/kg, 5.0 ug/kg, respectively.
      Excellent repeatability and reproducibility were also achieved. This highly
      sensitive and robust LC-MS/MS technique was applied successfully for the
      detection and quantification of MSG in a wide variety of foodstuffs. MSG contents
      ranged from 0.01 g/100 g to 15.39 g/100 g in food samples. Importantly,
      determination of free glutamic acid in the daily diet could also prevent various
      side effects associated with consumption of excess free glutamic acid.

PMID- 29329875
TI  - Hydrolysers of modified mycotoxins in maize: alpha-Amylase and cellulase induce
      an underestimation of the total aflatoxin content.
AB  - Aflatoxins are the most potent genotoxic and carcinogenic mycotoxins. To date,
      research has only focused on the presence of free aflatoxins in agricultural
      commodities. Therefore, the main objective of this study was to investigate the
      occurrence of possible modified aflatoxins in maize. Different hydrolysis methods
      were applied to convert modified mycotoxins into their free aflatoxins. Eighteen
      aflatoxin-contaminated maize samples were incubated with potassium hydroxide,
      trifluoromethanesulfonic acid and several enzymes to induce hydrolysis. Potassium
      hydroxide caused a total reduction of aflatoxins, while trifluoromethanesulfonic
      acid did not lead to an increase in free aflatoxins, neither did treatment with a
      protease. However, alpha-amylase and cellulase incubation caused significant
      increases in the total free aflatoxin content, 15 +/- 8% and 13 +/- 5%,
      respectively. These results show that a small proportion of aflatoxins could be
      associated to matrix substances in plants. Consequently, hydrolysis could occur
      during food processing and during mammalian digestion, leading to an
      underestimation of the total aflatoxin content.

PMID- 29329876
TI  - Discrimination of processing grades of olive oil and other vegetable oils by
      monochloropropanediol esters and glycidyl esters.
AB  - In this study, the processing derived contaminants 2- and 3-monochloropropanediol
      (2- and 3-MCPD) esters and glycidyl esters (GEs) were analysed in 84 oil samples
      by GC-MS/MS for the discrimination of processing grades of olive oils as a
      potential authentication tool. Concentrations of 2- and 3-MCPD esters and GEs
      varied in the ranges 0-6 mg/kg, 0-1.5 mg/kg, and 0-1 mg/kg oil, respectively. The
      concentrations of the three compounds in lower grade olive oils were
      significantly higher (P < .001) than that in EVOO. A similar difference was
      observed for other refined and cold-pressed vegetable oils. The limit of fraud
      detection of lower grade oils in EVOO was 2% when using 3-MCPD esters, 5% for 2
      MCPD esters, and 13-14% for GEs based on calculations of virtual mixtures of the
      current sample set. Especially the MCPD esters appear very specific and promising
      for the detection of lower processing grade oils in EVOO.

PMID- 29329877
TI  - [Attitudes towards cow's milk protein allergy management by spanish
      gastroenterologist].
AB  - INTRODUCTION: Food allergy is an increasing health problem in the developed
      world. Cow's milk protein is the main cause of food allergy in infants. Without
      an appropriate diagnostic workup, there is a high risk of both over- and
      underdiagnosis and therefore, over and undertreatment. The objective of our study
      was to analyze the variability in cow's milk protein allergy (CMPA) management by
      pediatric gastroenterologists in Spain. METHODS: A fifty item questionnaire,
      including open and closed items in a Likert's scale from 0 to 5, was drafted and
      distributed through the Spanish Society for Pediatric Gastroenterology,
      Hepatology and Nutrition (SEGHNP) e-mail list. RESULTS: Seventy-three
      questionnaires were received back out of 321. Only 3 of the items achieved
      concordance greater than 90%. Thirty-three percent considered oral challenge to
      be necessary for the diagnosis of CMPA under any circumstance. Twenty-five
      percent considered that symptom improvement after cow's milk removal was enough
      for the diagnosis. Oral challenge was performed at home by 83.5% in non-IgE
      mediated cases. Extensively hydrolyzed casein formulas were the treatment of
      choice for 69.9%. Soy formulas were the last option. Almost all respondents were
      aware of the existence of clinical guidelines on CMPA, being European Society of
      Pediatric Gastroenterology, Hepatology and Nutrition guidelines the most followed
      (64.4%). Twenty-three percent considered that their knowledge about allergy was
      inadequate. CONCLUSIONS: Although CMPA is a prevalent condition that pediatric
      gastroenterologists have been treating for decades, we found a huge variability
      on its management. There is potential for improvement in this field among
      pediatric gastroenterologist in the future.

PMID- 29329878
TI  - Course-, dose-, and stage-dependent toxic effects of prenatal dexamethasone
      exposure on fetal articular cartilage development.
AB  - Dexamethasone, a synthetic long-acting glucocorticoid, is routinely used for
      treating mothers at risk for preterm delivery. However, intrauterine overexposure
      to glucocorticoids induces low birth weight and cartilage dysplasia in offspring.
      Also, the "critical window" and safe dose of this treatment are largely unknown.
      This study investigated the course-, dose-, and stage-dependent toxic effects and
      the possible mechanisms of prenatal dexamethasone exposure (PDE) on fetal
      development and articular cartilage development. Pregnant mice (C57BL/6) received
      subcutaneous injection of dexamethasone (0.8 mg/kg d) once on gestational day
      (GD) 15 or once a day from GD 15 to 17, or received various doses of
      dexamethasone (0, 0.2, 0.8, and 1.2 mg/kg d) on GD 15-17, or received
      dexamethasone (0.8 mg/kg d) at early stage (GD 12-14) or late stage of pregnancy
      (GD 15-17). Offspring's knee joints were harvested at birth for morphological
      analyses and detection of gene expression. Repeated PDE significantly suppressed
      fetal and articular cartilage development, which were characterized by decreased
      body weight and body length, coarse articular cartilage surfaces, and reduced
      gene and protein expression of Col2a1 and aggrecan. For those newborns treated
      with repeated PDE at different doses, the toxic effects on fetal and articular
      cartilage development were observed at doses of 0.8 and 1.2 mg/kg d, whereas no
      obvious toxic effects were observed at the dose of 0.2 mg/kg d. Moreover, PDE at
      0.8 mg/kg d during the early embryonic stage induced stronger toxic effects on
      fetal and articular cartilage development, compared with PDE during the late
      embryonic stage. Detection of gene expression showed that the TGFbeta signaling
      pathway in the articular cartilage was down-regulated after PDE. Taken together,
      PDE induces fetal developmental toxicity and articular cartilage developmental
      toxicity in a course-, dose-, and stage-dependent manner.

PMID- 29329879
TI  - MiR-134 modulates chronic stress-induced structural plasticity and depression
      like behaviors via downregulation of Limk1/cofilin signaling in rats.
AB  - Increasing evidence has suggested that depression is a neuropsychiatric condition
      associated with neuroplasticity within specific brain regions. However, the
      mechanisms by which neuroplasticity exerts its effects in depression remain
      largely uncharacterized. In the present study we show that chronic stress
      effectively induces depression-like behaviors in rats, an effect which was
      associated with structural changes in dendritic spines and synapse abnormalities
      within neurons of the ventromedial prefrontal cortex (vmPFC). Moreover,
      unpredictable chronic mild stress (UCMS) exposure significantly increased the
      expression of miR-134 within the vmPFC, an effect which was paralleled with a
      decrease in the levels of expression and phosphorylation of the synapse
      associated proteins, LIM-domain kinase 1 (Limk1) and cofilin. An intracerebral
      infusion of the adenovirus associated virus (AAV)-miR-134-sponge into the vmPFC
      of stressed rats, which blocks mir-134 function, significantly ameliorated
      neuronal structural abnormalities, biochemical changes and depression-like
      behaviors. Chronic administration of ginsenoside Rg1 (40 mg/kg, 5 weeks), a
      potential neuroprotective agent extracted from ginseng, significantly ameliorated
      the behavioral and biochemical changes induced by UCMS exposure. These results
      suggest that miR-134-mediated dysregulation of structural plasticity may be
      related to the display of depression-like behaviors in stressed rats. The
      neuroprotective effects of ginsenoside Rg1, which produces an antidepressant like
      effect in this model of depression, appears to result from modulation of the miR
      134 signaling pathway within the vmPFC.

PMID- 29329880
TI  - Novel expression of CD11b in epithelial ovarian cancer: Potential therapeutic
      target.
AB  - OBJECTIVE: The objective of this study was to determine the expression, and
      effect of targeting CD11b with a monoclonal antibody in ovarian cancer cells.
      METHODS: CD11b expression was determined in epithelial ovarian cancer (EOC) cell
      lines and tissues by immunofluorescence and flow cytometry. Cytotoxicity of the
      CD11b antibody and synergism with chemothearapeutic drugs were determined by the
      MTT Cell Proliferation Assay in human macrophages, normal ovarian epithelial
      cells, and in both sensitive and chemoresistant EOC cell lines. Cell migration
      was assessed with a scratch assay and in vivo effects of the CD11b antibody was
      assessed with a nude mouse ovarian cancer xenograft model. Data was analyzed with
      either t-tests or one-way ANOVA. RESULTS: CD11b was unexpectedly expressed in
      several EOC lines and tissues, but not normal tissues. Targeting CD11b with its
      monoclonal antibody resulted in intriguing cytotoxic effects in sensitive and
      chemoresistant EOC lines, while surprisingly not affecting normal cells. More
      importantly, the cytotoxicity of the CD11b antibody when combined with
      chemotherapeutic drugs (cisplatin or docetaxel) was significantly synergistic, in
      both sensitive and chemoresistant EOC cells. The anti-tumorigenic effect of the
      CD11b antibody was confirmed in an ovarian cancer nude mouse xenograft model.
      CONCLUSION: Here we identify CD11b as a novel target, which selectively induces
      cytotoxicity in ovarian cancer cells.

PMID- 29329881
TI  - Defining and mitigating the challenges of an older and obese population in
      minimally invasive gynecologic cancer surgery.
AB  - The incidence of endometrial cancer (EC) is steadily increasing due in large part
      to an aging world population and rise in rates of obesity. Patients with obesity
      and advancing age can be seen as vulnerable populations, as they are both often
      subject to physician bias regarding surgical choices and assumptions regarding
      long-term outcomes. As we operate on an older and/or obese patient population, it
      is increasingly important that we adopt peri-operative management strategies and
      surgical techniques to best serve this complex patient population. Careful
      orchestration pre-, intra- and postoperatively is key to successful outcomes in
      robotic and laparoscopic surgery. Here, we review existing literature regarding
      EC in women with older age and/or obesity, outline recommendations for peri
      operative management and common intra-operative issues-specifically common
      anesthetic issues surrounding cardiovascular, respiratory and neuromuscular
      systems-that are of heightened importance in women with older age and/or obesity.
      The goal of this review is to help define and mitigate common complications for
      these vulnerable patients with an EC diagnosis who, in accordance with carefully
      assessed health risks, can and should be offered standard of care surgery and
      treatment.

PMID- 29329882
TI  - Prognostic significance of residual lymph node status after definitive
      chemoradiotherapy in patients with node-positive cervical cancer.
AB  - OBJECTIVE: Lymph node involvement is an important prognostic factor in patients
      with cervical cancer. However, the prognostic significance of lymph node response
      to chemoradiotherapy remains unclear. We retrospectively analyzed the
      relationship between residual lymph node status after definitive
      chemoradiotherapy and survival. METHODS: We enrolled 117 patients with node
      positive cervical cancer. All patients were treated with definitive
      chemoradiotherapy in our institution, from 2006 to 2016. The median follow-up
      period was 41months (range, 6-128months). The criterion for a positive lymph node
      was defined as a maximum short axis diameter of >=8mm on pretreatment magnetic
      resonance imaging (MRI)/computed tomography (CT) scans. Posttreatment pelvic MRI
      was obtained 3months after the completion of chemoradiotherapy. Residual primary
      tumor was defined as any residual lesion identified upon clinical examination
      and/or MRI. Residual lymph node was defined as any lymph node with a short axis
      diameter of >=8mm posttreatment, according to MRI/CT. RESULTS: At follow-up,
      3months after chemoradiotherapy, we observed residual primary tumor in 30
      patients (25.6%), and residual lymph node in 31 patients (26.5%). The presence of
      residual lymph node was associated with worse overall survival according to
      multivariate analysis (hazard ratio, 3.04; 95% confidence interval, 1.43-6.44;
      p=0.004). In the 5-year time-dependent ROC analysis of survival prediction, the
      presence of residual lymph node showed an AUC value of 0.72. CONCLUSIONS: The
      presence of residual lymph node after chemoradiotherapy was associated with worse
      survival in patients with node-positive cervical cancer.

PMID- 29329883
TI  - Oxidation, Damage Mechanisms, and Reasons for Revision of Sequentially Annealed
      Highly Crosslinked Polyethylene in Total Knee Arthroplasty.
AB  - BACKGROUND: Sequentially annealed, highly crosslinked polyethylene (HXLPE) has
      been used clinically in total knee arthroplasty (TKA) for over a decade. However,
      little is known about the revision reasons; its surface damage mechanisms; or its
      in vivo oxidative stability relative to conventional polyethylene. We asked
      whether retrieved HLXPE tibial inserts exhibited: (1) similar revision reasons;
      (2) improved resistance to surface damage; and (3) improved oxidative stability,
      when compared with conventional gamma inert sterilized polyethylene inserts.
      METHODS: A total of 456 revised tibial inserts were collected in a multicenter
      retrieval program between 2000 and 2016. The implantation time for the HXLPE
      components was 1.8 +/- 1.8 years, and for the control inserts it was 3.4 +/- 2.7
      years. Revision reasons were assessed based on medical records, radiographs, and
      examinations of the retrieved components. Surface damage was assessed using a
      semi-quantitative scoring method. Oxidation was measured using Fourier transform
      infrared spectroscopy. RESULTS: The tibial inserts in both cohorts were revised
      most frequently for loosening, infection, and instability. The most commonly
      observed surface damage modes were burnishing, pitting, and scratching. Oxidation
      of the HXLPE inserts was, on average, low and similar to the control inserts at
      the bearing surface and the stabilizing post. CONCLUSIONS: We observed evidence
      of in vivo oxidation in both HXLPE and control tibial inserts. We found no
      association between the levels of oxidation and the clinical performance of the
      HXLPE tibial components. The findings of this study document the revision
      reasons, surface damage modes, and oxidative behavior of sequentially annealed
      HXLPE for TKA.

PMID- 29329884
TI  - Impurity profiling of drug candidates: Analytical strategies using reversed-phase
      and mixed-mode high-performance liquid chromatography methods.
AB  - The development of new active pharmaceutical ingredients (API) requires accurate
      impurity profiling. Nowadays, reversed-phase HPLC (RPLC) on C18 stationary phase
      is the method of first choice for this task and usually employed in generic
      screening methods. However, this method sometimes fails, especially when the
      target analyte is not sufficiently retained, making impurity analysis difficult
      or even impossible. In such cases, a second method must be available. In the
      present paper, we compare the merits of RPLC on C18 phase to those of previously
      optimized alternative methods, based on the analysis of a large and diverse set
      of small-molecule drug candidates. Various strategies are considered: RPLC on C18
      phase but with different mobile phase composition (acidic or basic), RPLC with a
      pentafluorophenyl stationary phase, or mixed-mode HPLC with both bimodal and
      trimodal stationary phases. First, method performances were compared in terms of
      response rate (proportion of compounds eluted) and peak shapes for a large set of
      synthetic drugs (140) with structural diversity and their orthogonality was
      evaluated. Then a subset of compounds (25) containing varied impurity profiles
      was used to compare the methods based on the capability to detect impurities and
      evaluate the relative purity of the API.

PMID- 29329885
TI  - InnOscent system: Advancing flavor analysis using an original gas chromatographic
      analytical device.
AB  - Despite continuous advances in analytical and physiological knowledge, the
      comprehension of an aroma is still a challenge. Gas chromatography coupled to
      olfactometry (GC-O) is an efficient method to identify and estimate individual
      potential of odorants, but there is a gap between this individual
      characterization and the effective contribution of compounds in the mixture,
      which is due to complex chemical and perceptual interactions. Therefore,
      recombination and omission experiments are often performed to achieve an
      understanding of food aromas. In this study, a chromatographic device, developed
      to facilitate aroma analysis, is presented. It was configured to perform both (1)
      conventional analyses by GC coupled with a mass spectrometer, olfactometric
      port(s), and a flame ionization detector (FID), and (2) omission or recombination
      experiments. This dual capability is due to the singular configuration of the
      system using an ingenious combination of splitter and Deans switch microfluidics
      transfer modules, and the existence of multiple outlets. The operational status
      of the system was tested using a purposely simple mixture of compounds. The
      similarity of retention times (RT) and FID peak areas obtained for each outlet
      demonstrates that the multiple outlets of the system are equivalent. The
      reproducibility of retention times (RT) and FID peak areas obtained in switching
      and non-switching conditions, also demonstrates the efficiency of switching
      operations. The validation of the system enables multiple detectors to be
      connected to the outlets and complementary information can be obtained from the
      eluate. The connection of recovery disposals to the outlets provides fraction
      collection and recombination possibilities, which contribute much to the
      understanding of aroma-aroma interactions. As an illustration of the InnOscent
      system relevance for the comprehension of more complex aromas, the device was
      used to study the aroma of a wine made from Cabernet Franc grape variety. An
      olfactometric profile was efficiently produced with the device configured as a GC
      MS coupled to a dual olfactometric port. The main odorant active compounds were
      identified. The omission approach, carried out with the system on isopropyl- and
      isobutyl-methoxypyrazines, demonstrates the significant contribution of these
      compounds to the aroma of the wine studied, despite an individual perception
      among the weakest of the aromagram. A similar approach can be used to evaluate
      the contribution of any compound to any aroma. This approach overcomes
      constraints of current methodologies associated to reconstituted model solutions
      and paves the way for a better understanding of aroma construction.

PMID- 29329886
TI  - Solid-phase extraction of chlorophenols in seawater using a magnetic ionic liquid
      molecularly imprinted polymer with incorporated silicon dioxide as a sorbent.
AB  - A type of magnetic ionic liquid based molecularly imprinted polymer coated on
      SiO2 (Fe3O4@SiO2@IL-MIPs) was prepared with 1-vinyl-3-ethylimidazole ionic liquid
      as functional monomer, and 1,4-butane-3,3'-bis-1-ethylimidazole ionic liquid as
      cross linker, 4-Chlorophenol as template was successfully applied as a selective
      adsorbent for selective extraction of 5 chlorophenols in seawater samples by
      using the magnetic solid-phase extraction (MSPE) method. 11 types of
      Fe3O4@SiO2@IL-MIPs were synthesized and investigated for their different
      compositions of functional monomer (such as [C2min][Br], [C2min][BF4],
      [C2min][PF6], acrylamide, methacrylic acid and 4-vinyl pyridine) and cross-linker
      (such as [C4min2][Br], [C4min2][BF4], [C4min2][PF6], divinylbenzene, and ethylene
      glycol dimethacrylate), respectively. The [C2min][BF4] and [C4min2][PF6] based
      Fe3O4@SiO2@IL-MIP with the highest extraction efficiencies was applied to the
      optimization experiment of MSPE process (including extraction time, adsorbent
      mass and desorption solvents). Good linearity was obtained with correlation
      coefficients (R2) over 0.9990 and the relative standard deviations for the intra
      day and inter-day determination were less than 3.10% with the extraction
      recoveries ranged from 85.0% to 98.4%. The results indicated that the proposed
      Fe3O4@SiO2@IL-MIPs possesses great identification and adsorption properties, and
      could be used as a good sorbent for selective extraction of CPs in environment
      waters.

PMID- 29329887
TI  - Determination of N-glycans by high performance liquid chromatography using 6
      aminoquinolyl-N-hydroxysuccinimidyl carbamate as the glycosylamine labeling
      reagent.
AB  - Robust, efficient identification and accurate quantification of N-glycans are of
      great significance in N-glycomics analysis. Here, a simple and rapid
      derivatization method, based on the combination of microwave-assisted
      deglycosylation and 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC)
      labeling, was developed for the analysis of N-glycan by high performance liquid
      chromatography with fluorescence detection (HPLC-FLD). After optimizing various
      parameters affecting deglycosylation and derivatization by RNase B, the time for
      N-glycan labeling was shortened to 50 min with ~10-fold enhancement in detection
      sensitivity comparing to conventional 2-aminobenzoic acid (2-AA) labeling method.
      Additionally, the method showed good linearity (correlation coefficients > 0.991)
      and reproducibility (RSD < 8.7%). These advantages of the proposed method were
      further validated by the analysis of complex samples, including fetuin and human
      serum. Investigation of serum N-glycome for preliminary diagnosis of human lung
      cancer was conducted, where significant changes of several N-glycans
      corresponding to core-fucosylated, mono- and disialylated glycans have been
      evidenced by a series of statistical analysis.

PMID- 29329888
TI  - Associations between cartilage proteoglycan density and patient outcomes 12months
      following anterior cruciate ligament reconstruction.
AB  - BACKGROUND: Lower proteoglycan density (PGD) of the articular cartilage may be an
      early marker of osteoarthritis following anterior cruciate ligament (ACL)
      reconstruction (ACL-R). The purpose this study was to determine associations
      between the Knee Injury and Osteoarthritis Outcomes Score (KOOS) and PGD of the
      articular cartilage in the femur and tibia 12-months following ACL-R. METHODS: We
      evaluated KOOS pain, symptoms, function in activities of daily living (ADL),
      function in sport and recreation (Sport), and quality of life (QOL), as well as
      PGD using T1rho magnetic resonance imaging in 18 individuals 12.50+/-0.70months
      (these are all mean+/-standard deviation) following unilateral ACL-R (10 females,
      eight males; 22.39+/-4.19years; Marx Score=10.93+/-3.33). Medial and lateral load
      bearing portions of the femoral and tibial condyles were sectioned into three
      (anterior, central and posterior) regions of interest (ROIs). T1rho relaxation
      times in the ACL-R knee were normalized to the same regions of interest in the
      non-surgical knees. Alpha levels were set at P<=0.05. RESULTS: Worse KOOS
      outcomes were significantly associated with greater T1rho relaxation time ratios
      in the posterior-lateral femoral condyle [pain (r=-0.54), ADL (r=-0.56), Sport
      (r=-0.62) and QOL (r=-0.59)] central-lateral femoral condyle [Sport (r=-0.48) and
      QOL (r=-0.42)], and the anterior-medial femoral condyle [Sport (r=-0.46) and QOL
      (r=-0.40)]. There were no significant associations between the KOOS and T1rho
      outcomes for tibial ROI. CONCLUSIONS: Lower PGD of the femoral cartilage in the
      ACL-R knees was associated with worse patient-reported outcomes.

PMID- 29329889
TI  - Exploring individual adaptations to an anterior cruciate ligament injury
      prevention programme.
AB  - BACKGROUND: Individual responses to anterior cruciate ligament injury prevention
      programmes (ACL IPPs) have received little attention. This study examined the
      effects of an ACL IPP on neuromuscular control and lower limb biomechanics during
      landing at the group and individual levels. METHODS: Sixteen female athletes were
      randomly allocated to training (n=8) or control (n=8) groups. Electromyography,
      and three-dimensional kinematic and kinetic data were collected during landing at
      two testing sessions. Repeated measures ANOVA and effect sizes (Cohen's d)
      examined the effect of the IPP at the group and individual levels. A sub-group
      analysis comparing the effect of the IPP on 'high-' (i.e. large peak knee
      abduction moment at baseline) versus 'low-risk' individuals was also conducted.
      RESULTS: At the group level; the IPP increased activation of the medial
      hamstrings prior to landing (p<0.001; d=0.264) and the medial gastrocnemius at
      landing (p<0.001; d=0.426), and increased hip external rotation early after
      initial contact (p<0.001; d=0.476). Variable adaptations were seen across
      individuals within the training group for all variables (p<0.001). The IPP had a
      large effect in reducing frontal plane knee moments for 'high-risk' individuals
      (d>0.91), however these results did not reach statistical significance (p>0.05).
      CONCLUSIONS: The IPP induced adaptations during landing, however, individual data
      revealed dissimilar responses to the programme. Individuals displaying a pre
      existing high-risk strategy may incur greater benefits from IPPs, yet only if the
      programme targets the relevant high-risk strategy.

PMID- 29329890
TI  - Pain, motion and function comparison of two exercise protocols for the rotator
      cuff and scapular stabilizers in patients with subacromial syndrome.
AB  - STUDY DESIGN: Randomized clinical trial. INTRODUCTION: Eccentric exercise (EE)
      was shown to be an effective treatment in tendinopathies. However, the evidence
      of its effectiveness in subacromial syndrome (SS) is scarce. Moreover, consensus
      has not been reached on whether best results for SS are obtained by means of EE
      with or without pain. PURPOSE OF THE STUDY: The purpose of this is to compare the
      effect on pain, active range of motion (AROM), and shoulder function of an
      exercise protocol performed with pain <40 mm Visual Analog Scale (VAS) and
      without pain, in patients with SS. METHODS: Twenty-two subjects (mean age: 59
      years [Q1 = 48.50-Q3 = 70], 54.5% women) were randomized into a not-painful EE
      group (NPEE; G0: n = 11) and a painful EE group (PEE; G1: n = 11). The
      intervention lasted 4 weeks. Pain was recorded using VAS; AROM was measured using
      a goniometer; and shoulder function using the modified Constant-Murley Score
      (CMS) before and after intervention. RESULTS: All dependent variables improved
      significantly in both groups (P < .05): NPEE VAS median: pretest = 55.0 posttest
      = 28.0; CMS median: pretest = 36.0 posttest = 65.0. PEE VAS median: pretest =
      37.0 posttest = 12.0; CMS median: pretest = 35.0 posttest = 59.0. The comparison
      between groups showed no significant differences, with small effect size values
      (VAS = 0.09; CMS = 0.21; AROM = 0.12-0.43). DISCUSSION: In contrast to the
      previous findings, our results suggest that PEE do not add benefit in SS patients
      compared to NPEE. CONCLUSION: Our results suggest that both interventions are
      effective in terms of pain, function, and shoulder AROM. Furthermore, PEE does
      not provide greater benefits. Further studies are needed with long-term follow-up
      to reinforce these results.

PMID- 29329891
TI  - Medical use of cannabis and cannabinoids containing products - Regulations in
      Europe and North America.
AB  - In 1937, the United States of America criminalized the use of cannabis and as a
      result its use decreased rapidly. In recent decades, there is a growing interest
      in the wide range of medical uses of cannabis and its constituents; however, the
      laws and regulations are substantially different between countries. Laws
      differentiate between raw herbal cannabis, cannabis extracts, and cannabinoid
      based medicines. Both the European Medicines Agency (EMA) and the United States
      Food and Drug Administration (FDA) do not approve the use of herbal cannabis or
      its extracts. The FDA approved several cannabinoid-based medicines, so did 23
      European countries and Canada. However, only four of the reviewed countries have
      fully authorized the medical use of herbal cannabis - Canada, Germany, Israel and
      the Netherlands, together with more than 50% of the states in the United States.
      Most of the regulators allow the physicians to decide what specific indications
      they will prescribe cannabis for, but some regulators dictate only specific
      indications. The aim of this article is to review the current (as of November
      2017) regulations of medical cannabis use in Europe and North America.

PMID- 29329892
TI  - Pressure to publish in the biomedical scientific field: Ethical conflicts or a
      possible obsessive-compulsive disorder?

PMID- 29329893
TI  - Effect of short- and long-term diabetes control on in-hospital and one year
      mortality rates in hospitalized patients with diabetic foot.
AB  - INTRODUCTION: It remains unclear whether diabetic patients with diabetic foot
      complications benefit from strict glycemic control during hospitalization The
      present study investigates the effect of short- and long-term diabetes control on
      hospital outcomes including: in-hospital and one year mortality rates, length of
      hospital stay and the rate of repeated admissions. METHODS: Type 2 diabetic
      patients (n = 341) were hospitalized for diabetic foot complications at Wolfson
      Medical Center over a 5 year period (2008-2012). The adequate short-term glycemic
      control was defined as average glucose levels between 110 and 180 mg/dL. HbA1c
      values below 7% were defined as adequate long-term glycemic control. RESULTS: The
      average glucose levels during hospitalization were 179 +/- 45 mg/dL and 40% of
      the measurements were between 110 and 180 mg/dL. Mean admission HBA1c levels were
      8.43% +/- 2.26%, and 31% of the values were below 7%. The mean length of hospital
      stay was 24.3 +/- 22.6 days, 15.0% of the patients needed surgical intervention
      during admission, the in-hospital mortality rate was 10.3%, and the rate of 1
      year readmission was 25.1%. Adequate diabetes control during hospitalization was
      not significantly associated with reduced in-hospital mortality (hazard ratio,
      0.454, 95% confidence interval 0.186-1.103, p = 0.081). However, adequate
      diabetes control during hospitalization lead to significantly decreased one year
      mortality (hazard ratio, 0.269, 95% confidence interval 0.707-0.101, p = 0.009).
      Adequate diabetes control during hospitalization did not affect the length of
      hospital stay or the rate of repeated admission. CONCLUSIONS: Improved glucose
      control during hospital admission (levels between 110 and 180 mg/dL) was
      associated with reduction of one year mortality.

PMID- 29329894
TI  - Neoadjuvant Dose Dense MVAC versus Gemcitabine and Cisplatin in Patients with cT3
      4aN0M0 Bladder Cancer Treated with Radical Cystectomy.
AB  - PURPOSE: Level I evidence supports the usefulness of neoadjuvant cisplatin based
      chemotherapy for muscle invasive bladder cancer. Since dose dense MVAC
      (methotrexate, vinblastine, doxorubicin and cisplatin) has mostly replaced
      traditional MVAC, we compared pathological response and survival rates in
      patients with locally advanced bladder cancer who received neoadjuvant
      chemotherapy with dose dense MVAC vs gemcitabine and cisplatin. MATERIALS AND
      METHODS: We retrospectively reviewed the records of patients with urothelial
      cancer who received neoadjuvant chemotherapy and underwent cystectomy at a total
      of 20 contributing institutions from 2000 to 2015. Patients with cT3-4aN0M0
      disease were selected for this analysis. The rates of ypT0N0 and ypT1N0 or less
      were compared between the gemcitabine and cisplatin, and dose dense MVAC
      regimens. Two multivariable Cox proportional hazards regression models of overall
      mortality were generated using preoperative and postoperative data. RESULTS: Of
      the patients who underwent neoadjuvant chemotherapy and radical cystectomy during
      the study period 319 met our inclusion criteria. A significantly lower rate of
      ypT0N0 was observed in the gemcitabine and cisplatin arm than in the dose dense
      MVAC arm (14.6% vs 28.0%, p = 0.005). The rate of ypT1N0 or less was 30.1% for
      gemcitabine and cisplatin compared to 41.0% for dose dense MVAC (p = 0.07). The
      mean Kaplan-Meier estimates of overall survival in the gemcitabine and cisplatin,
      and dose dense MVAC groups were 4.2 and 7.0 years, respectively (p = 0.001). On
      multivariable cox regression analysis based on preoperative data patients who
      received gemcitabine and cisplatin were at higher risk for death than patients
      who received dose dense MVAC (HR 2.07, 95% CI 1.25-3.42, p = 0.003). Lymph node
      invasion (HR 1.97, 95% CI 1.15-3.36, p = 0.01) and hydronephrosis (HR 2.18, 95%
      CI 1.43-3.30, p <0.001) were also associated with higher risk of death.
      CONCLUSIONS: In our retrospective cohort of patients with locally advanced
      bladder cancer dose dense MVAC was associated with higher complete pathological
      response and improved survival rates compared to gemcitabine and cisplatin. A
      clinical trial is warranted to validate these hypothesis generating results to
      test the superiority of neoadjuvant dose dense MVAC in patients with locally
      advanced bladder cancer.

PMID- 29329895
TI  - Long-Term Outcomes of Laser Prostatectomy for Storage Symptoms: Comparison of
      Serial 5-Year Followup Data between High Performance System Photoselective
      Vaporization and Holmium Laser Enucleation of the Prostate.
AB  - PURPOSE: We compared long-term storage symptom outcomes between photoselective
      laser vaporization of the prostate with a 120 W high performance system and
      holmium laser enucleation of the prostate. We also determined factors influencing
      postoperative improvement of storage symptoms in the long term. MATERIALS AND
      METHODS: Included in our study were 266 men, including 165 treated with prostate
      photoselective laser vaporization using a 120 W high performance system and 101
      treated with holmium laser enucleation of the prostate, on whom 60-month followup
      data were available. Outcomes were assessed serially 6, 12, 24, 36, 48 and 60
      months postoperatively using the International Prostate Symptom Score,
      uroflowmetry and the serum prostate specific antigen level. Postoperative
      improvement in storage symptoms was defined as a 50% or greater reduction in the
      subtotal storage symptom score at each followup visit after surgery compared to
      baseline. RESULTS: Improvements in frequency, urgency, nocturia, subtotal storage
      symptom scores and the quality of life index were maintained up to 60 months
      after photoselective laser vaporization or holmium laser enucleation of the
      prostate. There was no difference in the degree of improvement in storage
      symptoms or the percent of patients with postoperative improvement in storage
      symptoms between the 2 groups throughout the long-term followup. However, the
      holmium laser group showed greater improvement in voiding symptoms and quality of
      life than the laser vaporization group. On logistic regression analysis a higher
      baseline subtotal storage symptom score and a higher BOOI (Bladder Outlet
      Obstruction Index) were the factors influencing the improvement in storage
      symptoms 5 years after prostate photoselective laser vaporization or holmium
      laser enucleation. CONCLUSIONS: Our serial followup data suggest that storage
      symptom improvement was maintained throughout the long-term postoperative period
      for prostate photoselective laser vaporization with a 120 W high performance
      system and holmium laser enucleation without any difference between the 2
      surgeries. Also, more severe storage symptoms at baseline and a more severe BOOI
      predicted improved storage symptoms in the long term after each surgery.

PMID- 29329896
TI  - Open prostatectomy versus 180-W XPS GreenLight laser vaporization: Long-term
      functional outcome for prostatic adenomas>80 g.
AB  - INTRODUCTION: GreenLight photoselective vaporisation of the prostate (PVP) offers
      an endoscopic alternative to open prostatectomy (OP) for treatment of large
      adenomas. This study compares long-term functional outcome of both techniques in
      patients with Benign prostatic obstruction (BPO)>80g. MATERIAL AND METHOD: Data
      from patients who underwent surgical treatment for BPO>80g from January 2010 to
      February 2015 at our institution were retrospectively collected and compared
      according to surgical technique. Patient's demographics, surgeon's experience,
      operative data and long-term functional results were analyzed, using IPSS and
      International continence society (ICS) male questionnaire associated with Quality
      of life scores (IPSS-QL and ICS-QL). Predictors of long-term outcome were also
      assessed. RESULTS: In total, 111 consecutive patients, 57 PVP and 54 OP, were
      included in the study with a mean follow-up of 24 and 33 month respectively.
      Patient's age, Charlson score, preoperative IPSS and urinary retention rates were
      similar. Mean prostatic volume was superior in the OP group (142 versus 103g,
      P<0.001). Transfusion rate was lower after PVP (P=0.02), despite a more frequent
      anticoagulant use. Length of hospital stay and urinary catheterization were
      shorter after PVP (P<0.001), with however a higher rate of recatheterization
      (RR=4.74) and rehospitalization (RR=10.42). Long-term scores were better after OP
      for IPSS (1 versus 5, P<0.001), IPSS-QL, ICS, ICS-QL. On multivariate analysis,
      prostatic residual volume was the only predictor of long-term IPSS but not ICS.
      CONCLUSION: Long-term functional outcome are better after OP compared to PVP.
      However, PVP offers good results, allowing to safely operate patients taking
      anticoagulants, regardless of prostatic volume. Endoscopic enucleation may the
      compromise between both techniques. LEVEL OF EVIDENCE: 4.

PMID- 29329897
TI  - [Botulinium toxin and idiopathic overactive bladder: Multicentric contempory
      management in Bourgogne].
AB  - INTRODUCTION: Since 2014, OnabotulinumtoxinA Botox(r) (Allergan, Inc., Irvine,
      USA) represents a new therapeutic option for second-line treatment of idiopathic
      overactive bladder. The purpose of the current study was to evaluate practices of
      surgeons using onabotulinium toxin (BoNTA) in this indication. MATERIAL AND
      METHODS: All urogynecology centers of the country were asked in order to list all
      patients who were treated since marketing autorisation. Patient symptoms,
      previous treatments, paraclinic evaluations, data of surgery and the
      characteristics of the follow up were collected and analyzed. RESULTS: Six
      centers used BoNTA and five have accepted to participate. Ninety-seven patients
      have been identified. Sixty-eight first injections (70 %) were carried out with
      the strict frameworf of the marketing autorisation (urinary frequency, urinary
      urgency, urinary incontinence). All patients had at least two symptoms. In 69 %,
      Botulinum toxin was a second-line treatment after the failure of tibial
      neuromodulation or sacral neuromodulation. Urodynamic evaluation was carried out
      for 91 % of patients. The search for a post-void residual volume was observed for
      59 % of patients during the follow up. CONCLUSION: In our country, BoNTA
      injections for idiopathic overactive bladder are mainly effected after tibial
      neuromodulation or sacral neuromodulation failure. Diagnostic, operating and
      outcome evaluation practices are still very heterogeneous pleading for a greater
      standardization of this new therapy in this indication. LEVEL OF EVIDENCE: 3.

PMID- 29329898
TI  - [Prognostic of older age for patients with invasive-muscle-bladder cancer and
      treated by radical cystectomy].
AB  - INTRODUCTION: Bladder tumor is a disease of older persons, but can also occur in
      young adults, because certainly an influence of environmental factors and a
      change of lifestyle. The aim of our retrospective analysis is to assess and
      evaluate the extent of the prognostic impact of age on the carcinological
      prognosis of invasive-muscle-bladder cancer treated by total cystotomy. METHODS:
      To evaluate the association of patient age with pathological characteristics and
      recurrence-free and disease survival, we retrospectively reviewed 345 patients
      with invasive bladder cancer between January 2000 and January 2015. RESULTS: We
      divided our patients into two groups: patients under 65 years of age=150 cases
      (group 1), patients aged 65 years and over=195 cases (group 2). The 3-year
      survival rates for patients according to the age groups were 88% and 64%
      respectively, end the recurrence-free survival 66% and 28%. When age was analysed
      as a categorical variable, was associated with hydronephrosis (P=0.001), advanced
      pathological stage (P=0.034), high grade (P=0.026), nodal involvement (P=0.011)
      and lymphovascular invasion (P=0.008). The multivariate Cox model analysis showed
      that hydronephrosis and pathological stage was prognostic factors of survival
      (P=0.012 and P=0.035, respectively). Higher age is significantly associated with
      the risk of pathologically advanced disease and poorer global survival.
      CONCLUSION: This work allowed us to assert that advanced chronological age is
      significantly associated with an advanced pathological stage of the disease
      (volume, pT, grade, lymph nodes) and a low overall survival rate. This could be
      useful for selecting subjects who would require adjuvant therapy, as well as for
      planning early complementary therapies. LEVEL OF EVIDENCE: 3.

PMID- 29329899
TI  - Reply.

PMID- 29329900
TI  - The call for considering follicular helper T cells in IgG4-related disease.

PMID- 29329901
TI  - Effects of orthokeratology on axial length growth in myopic anisometropes.
AB  - PURPOSE: To investigate the effect of orthokeratology (ortho-k) lens wear on
      axial length (AL) growth in juvenile myopic anisometropes. METHODS: This
      retrospective study consisted of two parts. In Part One, 25 anisometropic
      participants (mean age, 11.2 +/- 1.9 years; 11 females and 14 males) were fitted
      with ortho-k lenses in the more myopic eye only, and the rate of AL growth was
      compared between the ortho-k lens wearing eye and the untreated contralateral eye
      over an average period of 23.1 +/- 8.3 months. In Part Two, 8 participants who
      developed myopia in the contralateral eye received ortho-k treatment in both eyes
      for an average of 12 months; the rate of AL growth before and after ortho-k
      treatment in the newly developed myopic eye was compared. RESULTS: In Part One,
      the rate of AL elongation in the ortho-k treated eye (0.08 +/- 0.15 mm/year) was
      significantly slower than in the contralateral eye (0.39 +/- 0.32 mm/year) (P <
      0.001). At the completion of Part One, 16 out of 25 participants (64%) developed
      myopia in the initially non-myopic eye. In Part Two, the rate of AL elongation
      after ortho-k treatment in the newly developed myopic eye (0.20 mm/year) was
      significantly slower than that before ortho-k treatment in the same eye (0.49
      mm/year) (P = 0.012). CONCLUSION: Ortho-k treatment slows AL growth in the more
      myopic eye of anisometropic patients; should the contralateral eye develop myopia
      in the future, ortho-k is capable of slowing down AL growth in that eye as well.

PMID- 29329902
TI  - Impact of vertical and horizontal malrotation on measurements of anteroposterior
      radiographs of the scapula: need for standardized images in modern omometry.
AB  - BACKGROUND: An increasing number of parameters measured on anteroposterior
      radiographs are used for the evaluation of the bony geometry of the scapula.
      Inhomogeneous acquisition of images is common because of the lack of
      standardization in radiographic positioning. Images with malrotation around the
      horizontal axis of the scapula are particularly frequent. We hypothesized that
      malrotated images would result in large variations in measured radiographic
      parameters and that image standardization using qualitative and semiquantitative
      "omometric" criteria would decrease these variations in measurements. "Omometry"
      is a newly introduced umbrella term that contains all standardized measurements
      on plain radiographs of the shoulder, analogous to the term "coxometry," which is
      widely used for the radiographic assessment of the osseous pelvis and hip.
      METHODS: In this experimental, cadaveric radiographic study, 7 dry-bone human
      scapula cadaveric specimens from anonymous donors were used to obtain 210
      radiographs. We incrementally rotated (steps of 3 degrees ) every scapula around
      its horizontal and vertical axis, with a total range of 42 degrees  per each
      axis. Then, we measured 5 radiographic parameters on every image and observed
      their change with malrotation. Furthermore, we introduced 4 omometric criteria
      defining an appropriate (presence of >=3 criteria) radiographic image to improve
      standardization of scapular image acquisition. RESULTS: Overall, measured values
      remained stable within a narrow range of +/-9 degrees  of malrotation. Beyond
      this range, values of all parameters significantly deviated (>+/-2 degrees ) from
      the initial value. Measurements on appropriate images were significantly less
      prone to deviation. Within the appropriate images, those with 4 criteria showed a
      higher specificity than those with 3 criteria. CONCLUSION: There is significant
      variation in values of measured radiographic parameters on anteroposterior
      radiographs of the scapula with substantially malrotated images. With the use of
      the 4 newly introduced semiquantitative and qualitative omometric criteria, which
      define an appropriate image, reliability of the measured parameters can be
      significantly improved.

PMID- 29329903
TI  - Response to Laumonerie et al regarding: "Rare implant-specific complications of
      the MoPyC radial head prosthesis".

PMID- 29329904
TI  - Assembly, maturation, and degradation of the supraspinatus enthesis.
AB  - The development of the rotator cuff enthesis is still poorly understood. The
      processes in the early and late developmental steps are gradually elucidated, but
      it is still unclear how cell activities are coordinated during development and
      maturation of the structured enthesis. This review summarizes current knowledge
      about development and age-related degradation of the supraspinatus enthesis.
      Healing and repair of an injured and degenerated supraspinatus enthesis also
      remain a challenge, as the original graded transitional tissue of the
      fibrocartilaginous insertion is not re-created after the tendon is surgically
      reattached to bone. Instead, mechanically inferior and disorganized tissue forms
      at the healing site because of scar tissue formation. Consequently, the enthesis
      never reaches mechanical properties comparable to those of the native enthesis.
      So far, no novel biologic healing approach has been successful in enhancing
      healing of the injured enthesis. The results revealed in this review imply the
      need for further research to pave the way for better treatment of patients with
      rotator cuff disorder.

PMID- 29329905
TI  - Consensus Recommendations for Evaluation, Interpretation, and Utilization of
      Computed Tomography and Magnetic Resonance Enterography in Patients With Small
      Bowel Crohn's Disease.
AB  - Computed tomography and magnetic resonance enterography have become routine small
      bowel imaging tests to evaluate patients with established or suspected Crohn's
      disease, but the interpretation and use of these imaging modalities can vary
      widely. A shared understanding of imaging findings, nomenclature, and utilization
      will improve the utility of these imaging techniques to guide treatment options,
      as well as assess for treatment response and complications. Representatives from
      the Society of Abdominal Radiology Crohn's Disease-Focused Panel, the Society of
      Pediatric Radiology, the American Gastroenterological Association, and other
      experts, systematically evaluated evidence for imaging findings associated with
      small bowel Crohn's disease enteric inflammation and established recommendations
      for the evaluation, interpretation, and use of computed tomography and magnetic
      resonance enterography in small bowel Crohn's disease. This work makes
      recommendations for imaging findings that indicate small bowel Crohn's disease,
      how inflammatory small bowel Crohn's disease and its complications should be
      described, elucidates potential extra-enteric findings that may be seen at
      imaging, and recommends that cross-sectional enterography should be performed at
      diagnosis of Crohn's disease and considered for small bowel Crohn's disease
      monitoring paradigms. A useful morphologic construct describing how imaging
      findings evolve with disease progression and response is described, and standard
      impressions for radiologic reports that convey meaningful information to
      gastroenterologists and surgeons are presented.

PMID- 29329906
TI  - Development of a quick bioassay for the evaluation of transmission properties of
      acquired prion diseases.
AB  - Evaluation of transmission properties is important for the differential diagnosis
      of a subgroup of acquired Creutzfeldt-Jakob disease (CJD) with methionine
      homozygosity at polymorphic codon 129 of the PRNP gene, an intermediate type
      abnormal prion protein (PrP), and kuru plaques, denoted as acquired CJD-MMiK. The
      present study aimed to develop a quick evaluation system of the transmission
      properties of acquired CJD-MMiK. In the PrP-humanized mice intraperitoneally
      inoculated with brain homogenates from an acquired CJD-MMiK patient, accumulation
      of abnormal PrP was observed in follicular dendritic cells of the spleen at 75
      days post-inoculation. The transmission properties of acquired CJD-MMiK were
      quite different from those of sporadic CJD with the same PRNP codon 129 genotype.
      Moreover, even at 14 days post-inoculation, the characteristic transmission
      properties of acquired CJD-MMiK could be detected. These findings suggest that
      the bioassay using follicular dendritic cells of the spleen, named as a FDC
      assay, can be an easy, time-saving, and useful method to distinguish acquired CJD
      MMiK from sporadic CJD.

PMID- 29329907
TI  - Influence of motor imagery on spinal reflex excitability of multiple muscles.
AB  - The effects of motor imagery on spinal reflexes such as the H-reflex are unclear.
      One reason for this is that the muscles that can be used to record spinal
      reflexes are limited to traditional evoking methods Recently, transcutaneous
      spinal cord stimulation has been used for inducing spinal reflexes from multiple
      muscles and we aimed to examine the effect of motor imagery on spinal reflexes
      from multiple muscles. Spinal reflexes evoked by transcutaneous spinal cord
      stimulation were recorded from six muscles from lower limbs during motor imagery
      of right wrist extension and ankle plantarflexion with maximum isometric
      contraction. During both imaginary tasks, facilitation of spinal reflexes was
      detected in the ankle ipsilateral plantarflexor and dorsiflexor muscles, but not
      in thigh, toe or contralateral lower limb muscles. These results suggest that
      motor imagery of isometric contraction facilitates spinal reflex excitability in
      muscles of the ipsilateral lower leg and the facilitation does not correspond to
      the imaginary involved muscles.

PMID- 29329908
TI  - Anatomical evidence for lateral hypothalamic innervation of the pontine A7
      catecholamine cell group in rat.
AB  - Substantial behavioral evidence exists to support the idea that the lateral
      hypothalamus (LH) makes axonal connection with spinally-projecting noradrenergic
      neurons of the A7 catecholamine cell group in the pons. Through this putative
      projection, the LH modulates nociception via alpha1- and alpha2-adrenoceptors in
      the dorsal horn. We used double-label immunocytochemistry to demonstrate that
      axons from the LH labeled with the anterograde tracer biotinylated dextran amine
      (BDA) appose tyrosine hydroxylase-immunoreactive (TH-ir) neuron profiles in the
      A7 area. Other pontine areas labeled with BDA included the dorsomedial tegmental
      area, the pontine reticular nucleus, oral part, the caudal aspect of the dorsal
      raphe, the periaqueductal grey and the A6 area. To confirm the findings of the
      brightfield experiment, we used confocal microscopy to identify axons from the LH
      labeled with the anterograde tracer Fluoro-Ruby co-localized with TH-ir dendrites
      and cell bodies in the A7 cell group. These findings provide an anatomical
      substrate for behavioral studies in which stimulation of the LH modifies
      nociception in the spinal cord via norepinephrine.

PMID- 29329911
TI  - mRNA expression and metabolic regulation of npy and agrp1/2 in the zebrafish
      brain.
AB  - Neuropeptide Y (NPY) is an evolutionarily conserved neuropeptide implicated in
      feeding regulation in vertebrates. In mammals, NPY neurons coexpress Agouti
      related protein (AgRP) in the arcuate nucleus of the hypothalamus, and NPY/AgRP
      neurons activate orexigenic signaling to increase food intake. Zebrafish express
      npy and two agrp genes, agrp1 and agrp2, in the brain. Similar to mammals, NPY
      and AgRP1 act as orexigenic factors in zebrafish, but the exact distribution of
      NPY and AgRP neurons in the zebrafish brain and the regulation of these genes by
      metabolic states remain unclear. In this study, we analyzed the tissue
      distribution of npy, agrp1, and agrp2 mRNA in the brain of larval and adult
      zebrafish. We detected the expression of agrp1, but not npy, in the hypothalamus
      of larval zebrafish. In the adult zebrafish brain, npy mRNA expression was
      detected in the dorsal area of the periventricular and lateral hypothalamus, but
      fasting induced upregulation of npy only in the lateral hypothalamus, indicating
      that NPY neurons in this area are implicated in feeding regulation. However,
      consistent with the findings in larval zebrafish, NPY neurons in the hypothalamus
      did not coexpress AgRP1. In contrast, fasting resulted in a dramatic increase in
      AgRP1 neurons in the ventral periventricular hypothalamus, which do not coexpress
      NPY. In addition, we found for the first time that npy- and agrp1-expressing
      neurons function as GABAergic inhibitory neurons in zebrafish, as they do in
      mammals. Taken together, our results show that the zebrafish NPY/AgRP system is
      involved in appetite regulation. In addition, our data suggest that although npy
      and agrp1 were initially expressed in distinct neurons, evolution has resulted in
      their coexpression in mammalian hypothalamic neurons.

PMID- 29329910
TI  - The effects of exercise intensity and post-exercise recovery time on cortical
      activation as revealed by EEG alpha peak frequency.
AB  - Acute physical exercise (APE) induces an increase in the individual alpha peak
      frequency (iAPF), a cortical parameter associated with neural information
      processing speed. The aim of this study was to further scrutinize the influence
      of different APE intensities on post-exercise iAPF as well as its time course
      after exercise cessation. 95 healthy young (18-35 years) subjects participated in
      two randomized controlled experiments (EX1 and EX2). In EX1, all participants
      completed a graded exercise test (GXT) until exhaustion and were randomly
      allocated into different delay groups (immediately 0, 30, 60 and 90 min after
      GXT). The iAPF was determined before, immediately after as well as after the
      group-specific delay following the GXT. In EX2, participants exercised for 35 min
      at either 45-50%, 65-70% or 85-90% of their maximum heart rate (HRmax). The iAPF
      was determined before, immediately after as well as 20 min after exercise
      cessation. In EX1, the iAPF was significantly increased immediately after the GXT
      in all groups. This effect was not any more detectable after 30 min following
      exercise cessation. In EX2, a significant increase of the iAPF was found only
      after high-intensity (85-90% HRmax) exercise. The results indicate intense or
      exhaustive physical exercise is required to induce a transient increase in the
      iAPF that persists about 30 min following exercise cessation. Based on these
      findings, further research will have to scrutinize the behavioral implications
      associated with iAPF modulations following exercise.

PMID- 29329913
TI  - Predicting Extubation Outcomes-A Model Incorporating Heart Rate Characteristics
      Index.
AB  - OBJECTIVE: To test the hypothesis that in neonates on mechanical ventilation,
      heart rate characteristics index (HRCi) can be combined with a clinical model for
      predicting extubation outcomes in neonates. STUDY DESIGN: HRCi and clinical data
      for all intended intubation-extubation events (episodes) were retrospectively
      analyzed between June 2014 and January 2015. Each episode started 6 hours pre
      extubation or at the time of primary intubation if ventilation duration was
      shorter than 6 hours (baseline). The episodes ended at 72 hours postextubation
      for successful extubations or at reintubation for failed extubations. Mean of 6
      hourly epoch HRCi-scores (baseline) or fold-changes (postextubation) were
      analyzed. Results are expressed as medians (IQR) for continuous data and
      proportions for categorical data. Multivariable logistic regression mixed model
      was used for statistical analysis. RESULTS: Sixty-six infants contributed to 96
      episodes (18 failed extubations, 78 successful extubations) in the study. Failed
      extubations had significantly longer duration of ventilation (65.3 hours, 19.94
      158.2 vs 38.4, 16.5-71.3) and more culture positive sepsis (33.3% vs 3.8%) than
      successful extubations. Baseline HRCi scores (1.68, 1.29-2.45 vs 0.95, 0.54-1.86)
      and postextubation epoch-1 fold changes (1.25, 0.94-1.55 vs 0.94, 0.82-1.11) were
      higher in failed extubations compared with successful extubations. Multivariable
      linear mixed-effects regression was used to create prediction models for success
      of extubation, using relevant variables. CONCLUSIONS: The baseline and
      postextubation HRCi were significantly higher in neonates with extubation failure
      compared with those who succeeded. Models using HRCi and clinical variables to
      predict extubation success may add to the confidence of clinicians considering
      extubation.

PMID- 29329914
TI  - Never Forget the Optic Fundi in Tuberculosis!

PMID- 29329912
TI  - Identification and fate mapping of the pancreatic mesenchyme.
AB  - The murine pancreas buds from the ventral embryonic endoderm at approximately
      8.75 dpc and a second pancreas bud emerges from the dorsal endoderm by 9.0 dpc.
      Although it is clear that secreted signals from adjacent mesoderm-derived sources
      are required for both the appropriate emergence and further refinement of the
      pancreatic endoderm, neither the exact signals nor the requisite tissue sources
      have been defined in mammalian systems. Herein we use DiI fate mapping of
      cultured murine embryos to identify the embryonic sources of both the early
      inductive and later condensed pancreatic mesenchyme. Despite being capable of
      supporting pancreas induction from dorsal endoderm in co-culture experiments, we
      find that in the context of the developing embryo, the dorsal aortae as well as
      the paraxial, intermediate, and lateral mesoderm derivatives only transiently
      associate with the dorsal pancreas bud, producing descendants that are decidedly
      anterior to the pancreas bud. Unlike these other mesoderm derivatives, the axial
      (notochord) descendants maintain association with the dorsal pre-pancreatic
      endoderm and early pancreas bud. This fate mapping data points to the notochord
      as the likely inductive source in vivo while also revealing dynamic morphogenetic
      movements displayed by individual mesodermal subtypes. Because none of the
      mesoderm examined above produced the pancreatic mesenchyme that condenses around
      the induced bud to support exocrine and endocrine differentiation, we also sought
      to identify the mesodermal origins of this mesenchyme. We identify a portion of
      the coelomic mesoderm that contributes to the condensed pancreatic mesenchyme. In
      conclusion, we identify a portion of the notochord as a likely source of the
      signals required to induce and maintain the early dorsal pancreas bud,
      demonstrate that the coelomic mesothelium contributes to the dorsal and ventral
      pancreatic mesenchyme, and provide insight into the dynamic morphological
      rearrangements of mesoderm-derived tissues during early organogenesis stages of
      mammalian development.

PMID- 29329909
TI  - The signaling role for chloride in the bidirectional communication between
      neurons and astrocytes.
AB  - It is well known that the electrical signaling in neuronal networks is modulated
      by chloride (Cl-) fluxes via the inhibitory GABAA and glycine receptors. Here, we
      discuss the putative contribution of Cl- fluxes and intracellular Cl- to other
      forms of information transfer in the CNS, namely the bidirectional communication
      between neurons and astrocytes. The manuscript (i) summarizes the generic
      functions of Cl- in cellular physiology, (ii) recaps molecular identities and
      properties of Cl- transporters and channels in neurons and astrocytes, and (iii)
      analyzes emerging studies implicating Cl- in the modulation of neuroglial
      communication. The existing literature suggests that neurons can alter astrocytic
      Cl- levels in a number of ways; via (a) the release of neurotransmitters and
      activation of glial transporters that have intrinsic Cl- conductance, (b) the
      metabotropic receptor-driven changes in activity of the electroneutral cation-Cl-
      cotransporter NKCC1, and (c) the transient, activity-dependent changes in glial
      cell volume which open the volume-regulated Cl-/anion channel VRAC. Reciprocally,
      astrocytes are thought to alter neuronal [Cl-]i through either (a) VRAC-mediated
      release of the inhibitory gliotransmitters, GABA and taurine, which open neuronal
      GABAA and glycine receptor/Cl- channels, or (b) the gliotransmitter-driven
      stimulation of NKCC1. The most important recent developments in this area are the
      identification of the molecular composition and functional heterogeneity of brain
      VRAC channels, and the discovery of a new cytosolic [Cl-] sensor - the Wnk family
      protein kinases. With new work in the field, our understanding of the role of Cl-
      in information processing within the CNS is expected to be significantly updated.

PMID- 29329915
TI  - Observed variation in N95 respirator use by nurses demonstrating isolation care.
AB  - Video review and scoring was used to evaluate the behaviors of nurses wearing N95
      filtering face piece respirators while providing isolation care in a simulated
      patient care environment. This study yielded a detailed description of behaviors
      related to N95 respirator use in a health care setting. Developing a more robust
      and systematic behavior analysis tool for use in demonstration, simulation, and
      clinical care would allow for improved respiratory protection of health care
      workers.

PMID- 29329917
TI  - Comments on incidence and risk factors for infection in spine surgery: A
      prospective multicenter study of 1,764 instrumented spine procedures.

PMID- 29329916
TI  - Impact of the International Nosocomial Infection Control Consortium's
      multidimensional approach on rates of ventilator-associated pneumonia in 14
      intensive care units in 11 hospitals of 5 cities within Argentina.
AB  - BACKGROUND: To analyze the impact of the International Nosocomial Infection
      Control Consortium (INICC) multidimensional approach (IMA) on ventilator
      associated pneumonia (VAP) rates in 11 hospitals within 5 cities of Argentina
      from January 2014-April 2017. METHODS: A multicenter, prospective, before-after
      surveillance study was conducted through the use of International Nosocomial
      Infection Control Consortium Surveillance Online System. During baseline, we
      performed outcome surveillance of VAP applying the definitions of the Centers for
      Disease Control andPrevention's National Healthcare Safety Network. During
      intervention, we implemented the IMA, which included a bundle of infection
      prevention practice interventions, education, outcome surveillance, process
      surveillance, feedback on VAP rates and consequences, and performance feedback of
      process surveillance. Bivariate and multivariate regression analyses were
      performed using a logistic regression model to estimate the effect of the
      intervention. RESULTS: We recorded 3,940 patients admitted to 14 intensive care
      units. At baseline, there were 19.9 VAPs per 1,000 mechanical ventilator (MV)
      days-with 2,920 MV-days and 58 VAPs, which was reduced during intervention to 9.4
      VAPs per 1,000 MV-days-with 9,261 MV-days and 103 VAPs. This accounted for a 52%
      rate reduction (incidence density rate, 0.48; 95% confidence interval, 0.3-0.7; P
      .001). CONCLUSIONS: Implementing the IMA was associated with significant
      reductions in VAP rates in intensive care units within Argentina.

PMID- 29329918
TI  - Trends in incidence of long-term-care facility onset Clostridium difficile
      infections in 10 US geographic locations during 2011-2015.
AB  - During 2011-2015, the adjusted long-term-care facility onset Clostridium
      difficile infection incidence rate in persons aged >=65 years decreased annually
      by 17.45% (95% confidence interval, 14.53%-20.43%) across 10 US sites. A
      concomitant decline in inpatient fluoroquinolone use and the C difficile epidemic
      strain NAP1/027 among persons aged >=65 years may have contributed to the
      decrease in long-term-care facility-onset C difficile infection incidence rate.

PMID- 29329919
TI  - Comments on risk factors for health care-associated infections: From better
      knowledge to better prevention.

PMID- 29329920
TI  - Comments on decreased mortality in patients prescribed vancomycin after
      implementation of an antimicrobial stewardship program.

PMID- 29329921
TI  - Assessment of test methods for evaluating effectiveness of cleaning flexible
      endoscopes.
AB  - BACKGROUND: Strict adherence to each step of reprocessing is imperative to
      removing potentially infectious agents. Multiple methods for verifying proper
      reprocessing exist; however, each presents challenges and limitations, and best
      practice within the industry has not been established. Our goal was to evaluate
      endoscope cleaning verification tests with particular interest in the evaluation
      of the manual cleaning step. The results of the cleaning verification tests were
      compared with microbial culturing to see if a positive cleaning verification test
      would be predictive of microbial growth. METHODS: This study was conducted at 2
      high-volume endoscopy units within a multisite health care system. Each of the 90
      endoscopes were tested for adenosine triphosphate, protein, microbial growth via
      agar plate, and rapid gram-negative culture via assay. The endoscopes were tested
      in 3 locations: the instrument channel, control knob, and elevator mechanism.
      RESULTS: This analysis showed substantial level of agreement between protein
      detection postmanual cleaning and protein detection post-high-level disinfection
      at the control head for scopes sampled sequentially. CONCLUSIONS: This study
      suggests that if protein is detected postmanual cleaning, there is a significant
      likelihood that protein will also be detected post-high-level disinfection. It
      also infers that a cleaning verification test is not predictive of microbial
      growth.

PMID- 29329922
TI  - A multistate investigation of health care-associated Burkholderia cepacia complex
      infections related to liquid docusate sodium contamination, January-October 2016.
AB  - BACKGROUND: Outbreaks of health care-associated infections (HAIs) caused by
      Burkholderia cepacia complex (Bcc) have been associated with medical devices and
      water-based products. Water is the most common raw ingredient in nonsterile
      liquid drugs, and the significance of organisms recovered from microbiologic
      testing during manufacturing is assessed using a risk-based approach. This
      incident demonstrates that lapses in manufacturing practices and quality control
      of nonsterile liquid drugs can have serious unintended consequences. METHODS: An
      epidemiologic and laboratory investigation of clusters of Bcc HAIs that occurred
      among critically ill, hospitalized, adult and pediatric patients was performed
      between January 1, 2016, and October 31, 2016. RESULTS: One hundred and eight
      case patients with Bcc infections at a variety of body sites were identified in
      12 states. Two distinct strains of Bcc were obtained from patient clinical
      cultures. These strains were found to be indistinguishable or closely related to
      2 strains of Bcc obtained from cultures of water used in the production of liquid
      docusate, and product that had been released to the market by manufacturer X.
      CONCLUSIONS: This investigation highlights the ability of bacteria present in
      nonsterile, liquid drugs to cause infections or colonization among susceptible
      patients. Prompt reporting and thorough investigation of potentially related
      infections may assist public health officials in identifying and removing
      contaminated products from the market when lapses in manufacturing occur.

PMID- 29329923
TI  - Different protein composition of low-calorie diet differently impacts adipokine
      profile irrespective of weight loss in overweight and obese women.
AB  - BACKGROUND AND AIMS: High-protein (HP) diets have shown benefits in
      cardiometabolic markers such as insulin or triglycerides but the responsible
      mechanisms are not known. We aimed to assess the effect of three energy
      restricted diets with different protein contents (20%, 27%, and 35%; ~80% coming
      from animal source) on plasma adipokine concentration and its association with
      changes in cardiometabolic markers. METHODS: Seventy-six women (BMI 32.8 +/-
      2.93) were randomized to one of three calorie-reduced diets, with protein, 20%,
      27%, or 35%; carbohydrates, 50%, 43%, or 35%; and fat, 30%, for 3 months. Plasma
      adipokine (leptin, resistin, adiponectin, and retinol-binding protein 4; RBP4)
      levels were assessed. RESULTS: After 3 months, leptin concentration decreased in
      all groups without differences among them, while resistin levels remained
      unchanged. Adiponectin concentration heterogeneously changed in all groups (P for
      trend = 0.165) and resistin concentration did not significantly change. RPB4
      significantly decreased by -17.5% (-31.7, -3.22) in 35%-protein diet (P for trend
      = 0.024 among diets). Triglycerides improved in women following the 35%-protein
      diet regardless of weight loss; RBP4 variation significantly influenced
      triglyceride concentration change by 24.9% and 25.9% when comparing 27%- and 35%-
      with 20%-protein diet, respectively. CONCLUSIONS: A 35%-protein diet induced a
      decrease in RBP4 regardless of weight loss, which was directly associated with
      triglyceride concentration improvement. These findings suggest that HP diets
      improve the cardiometabolic profile, at least in part, through changes in
      adipokine secretion. Whether this beneficial effect of HP diet is due to
      improvements in hepatic or adipose tissue functionality should be elucidated.
      CLINICAL TRIAL REGISTRATION: The clinical trial has been registered in
      ClinicalTrials.gov (Identifier: NCT02160496).

PMID- 29329924
TI  - Effects of dark chocolate on endothelial function in patients with non-alcoholic
      steatohepatitis.
AB  - BACKGROUND AND AIM: Oxidative stress plays a pivotal role in inducing endothelial
      dysfunction and progression from simple fatty liver steatosis (FLD) to non
      alcoholic steatohepatitis (NASH). Polyphenols could reduce oxidative stress and
      restore endothelial function by inhibiting the nicotinamide-adenine-dinucleotide
      phosphate (NADPH) oxidase isoform Nox2. The aim of this study was to assess
      endothelial function and oxidative stress in a population affected by simple FLD
      and NASH. Furthermore, we analysed the effect of high vs low content of cocoa
      polyphenols on endothelial function and oxidative stress in patients with NASH.
      METHODS: In a cross-sectional study we analysed endothelial function, as assessed
      by flow-mediated dilation (FMD), and oxidative stress, as assessed by Nox2
      activation, serum isoprostanes and nitric oxide bioavailability (NOx), in
      patients with NASH (n = 19), FLD (n = 19) and controls (n = 19). Then, we
      performed a randomized, cross-over study in 19 subjects with NASH comparing the
      effect of 14-days administration of 40 g of chocolate at high (dark chocolate,
      cocoa >85%) versus low content (milk chocolate, cocoa <35%) of polyphenols on FMD
      and oxidative stress. Compared to controls, NASH and FLD patients had higher Nox2
      activity and isoprostanes levels and lower FMD and NOx, with a significant
      gradient between FLD and NASH. The interventional study showed that, compared to
      baseline, FMD and NOx increased (from 2.9 +/- 2.4 to 7.2 +/- 3.0% p < 0.001 and
      from 15.9 +/- 3.6 to 20.6 +/- 4.9 MUM, p < 0.001, respectively) in subjects given
      dark but not in those given milk chocolate. A simple linear regression analysis
      showed that Delta (expressed by difference of values between before and after 14
      days of chocolate assumption) of FMD was associated with Delta of Nox2 activity
      (Rs = -0.323; p = 0.04), serum isoprostanes (Rs: -0.553; p < 0.001) and NOx (Rs:
      0.557; p < 0.001). CONCLUSIONS: Cocoa polyphenols improve endothelial function
      via Nox2 down-regulation in NASH patients.

PMID- 29329925
TI  - Phenotypic and molecular characterization of a serum-free miniature erythroid
      differentiation system suitable for high-throughput screening and single-cell
      assays.
AB  - In vitro erythroid differentiation systems are used to study the mechanisms
      underlying normal and abnormal erythropoiesis and to test the effects of various
      extracellular factors on erythropoiesis. The use of serum or conditioned medium
      in liquid cultures and the seeding of cultures with heterogeneous peripheral
      blood mononuclear cells confound the reproducibility of these systems. Newer
      erythroid differentiation culture systems have overcome some of these limitations
      by using a fully defined, serum-free medium and initiating cultures using
      purified CD34+ cells. Although widely used in bulk cultures, these protocols have
      not been rigorously tested in high-throughput or single-cell assays. Here, we
      describe a serum-free erythroid differentiation system suitable for small-scale
      and single-cell experiments. This system generates large numbers of terminally
      differentiated erythroid cells of very high purity. Here we have adapted this
      culture system to a 96-well format and have developed a protocol to grow
      erythroid colonies from single erythroid progenitors in minute culture volumes.

PMID- 29329926
TI  - Characterization of Selenoprotein P cDNA of the Antarctic toothfish Dissostichus
      mawsoni and its role under cold pressure.
AB  - Our previous study using comparative genome analysis revealed a significant gene
      copy number gain of Dissostichus mawsoni selenoprotein P (Dm-SEPP) during the
      evolutionary radiation of Antarctic notothenioids, suggesting that Dm-SEPP
      contribute to this process, but the detailed structure and function of this gene
      product remain unclear. In the present study, the Dm-SEPP cDNA was cloned and
      characterized. The Dm-SEPP cDNA contains 17 selenocysteines (Sec) encoded by TGA
      codons and 2 typical SECIS elements located in the 3'-UTR. Evolutionary analysis
      of the Dm-SEPP gene revealed that it's closely related to the SEPP gene of
      zebrafish (Danio rerio), showing 51% amino acid similarity. Over-expression of Dm
      SEPP could protect mammalian cells under cold pressure, probably via eliminating
      ROS. Further study showed an increase of endogenous SEPP in zebrafish ZF4 cells
      under cold pressure, and knockdown of SEPP decreased cell viability, accompanied
      with increased ROS. Our results suggested a protective role of Dm-SEPP in cold
      adaptation in Antarctic notothenioids.

PMID- 29329927
TI  - Systems biomarkers in psoriasis: Integrative evaluation of computational and
      experimental data at transcript and protein levels.
AB  - Psoriasis is a complex autoimmune disease with multiple genes and proteins being
      involved in its pathogenesis. Despite the efforts performed to understand
      mechanisms of psoriasis pathogenesis and to identify diagnostic and prognostic
      targets, disease-specific and effective biomarkers were still not available. This
      study is compiled regarding clinical validation of computationally proposed
      biomarkers at gene and protein expression levels through qRT-PCR and ELISA
      techniques using skin biopsies and blood plasma. We identified several gene and
      protein clusters as systems biomarkers and presented the importance of gender
      difference in psoriasis. A gene cluster comprising of PI3, IRF9, IFIT1 and NMI
      were found as positively correlated and differentially co-expressed for women,
      whereas SUB1 gene was also included in this cluster for men. The differential
      expressions of IRF9 and NMI in women and SUB1 in men were validated at gene
      expression level via qRT-PCR. At protein level, PI3 was abundance in disease
      states of both genders, whereas PC4 protein and WIF1 protein were significantly
      higher in healthy states than disease states of male group and female group,
      respectively. Regarding abundancy of PI3 and WIF1 proteins in women, and PI3 and
      PC4 in men may be assumed as systems biomarkers at protein level.

PMID- 29329928
TI  - Cloning and characterization of ?6/?5 fatty acyl desaturase (Fad) gene promoter
      in the marine teleost Siganus canaliculatus.
AB  - The rabbitfish Siganus canaliculatus was the first marine teleost demonstrated to
      have the ability of biosynthesizing long-chain polyunsaturated fatty acids (LC
      PUFA) from C18 PUFA precursors, and all genes encoding the key enzymes for LC
      PUFA biosynthesis have been cloned and functionally characterized, which provides
      us a potential model to study the regulatory mechanisms of LC-PUFA biosynthesis
      in teleosts. As the primary step to clarify such mechanisms, present research
      focused on promoter analysis of gene encoding ?6/?5 fatty acyl desaturase (Fad),
      a rate-limiting enzyme catalyzing the first step in the conversion of C18 PUFA to
      LC-PUFA. First, 2044 bp promoter sequence was cloned by genome walking, and the
      sequence from -456 bp to +51 bp was determined as core promoter by progressive
      deletion mutation. Moreover, binding sites of transcription factors (TF) such as
      CCAAT enhancer binding protein (C/EBP), nuclear factor 1 (NF-1), stimulatory
      protein 1 (Sp1), nuclear factor Y (NF-Y), activated protein 1 (AP1), sterol
      regulatory element (SRE), hepatocyte nuclear factor 4alpha (HNF4alpha) and
      peroxisome proliferator activated receptor gamma (PPARgamma) were identified in
      the core promoter by site-directed mutation and functional assays. Moreover, NF-1
      and HNF4alpha were confirmed to interact with the core promoter region by gel
      shift assay and mass spectrometry. This is the first report of the promoter
      structure of a ?6/?5 Fad in a marine teleost, and a novel discovery of NF-1 and
      HNF4alpha binding to the ?6/?5 Fad promoter.

PMID- 29329929
TI  - Detoxification genes polymorphisms in SIDS exposed to tobacco smoke.
AB  - The best hypothesis to explain Sudden Infant Death Syndrome (SIDS) pathogenesis
      is offered by the "triple risk model", which suggests that an interaction of
      different variables related to exogenous stressors and infant vulnerability may
      lead to the syndrome. Environmental factors are triggers that act during a
      particular sensible period, modulated by intrinsic genetic characteristics.
      Although literature data show that one of the major SIDS risk factors is smoking
      exposure, a specific involvement of molecular components has never been
      highlighted. Starting from these observations and considering the role of GSTT1
      and GSTM1 genes functional polymorphisms in the detoxification process, we
      analyzed GSTM1 and GSTT1 null genotype frequencies in 47 SIDS exposed to tobacco
      smoke and 75 healthy individuals. A significant association (p < .0001) between
      the GSTM1 null genotype and SIDS exposed to smoke was found. On the contrary, no
      association between GSTT1 polymorphism and SIDS was determined. Results indicated
      the contribution of the GSTM1 -/- genotype resulting in null detoxification
      activity in SIDS cases, and led to a better comprehension of the triple risk
      model, highlighting smoking exposure as a real SIDS risk factor on a biochemical
      basis.

PMID- 29329930
TI  - Ketamine is a good first-line option for severely agitated patients in the
      prehospital environment.

PMID- 29329931
TI  - Red blood cell distribution width in sepsis.

PMID- 29329933
TI  - Combined Hepatic and Pulmonary Metastasectomies From Colorectal Carcinoma. Data
      From the Prospective Spanish Registry 2008-2010.
AB  - INTRODUCTION: Resection of both liver and lung metastases from colorectal
      carcinoma (CRC) is a standard of care in selected patients with oligometastatic
      disease. We present here the analysis of the subgroup of patients undergoing
      combined surgery from the Spanish Group of Surgery of Pulmonary Metastases (PM)
      from Colorectal Carcinoma (GECMP-CCR-SEPAR). METHODS: We analyze characteristics,
      survival and prognostic factors of patients undergoing combined resection from
      March-2008 to February-2010 and followed-up during at least 3 years, from the
      prospective multicenter Spanish Registry. RESULTS: A total of 138 patients from a
      whole series of 543 cases from 32 thoracic surgery units underwent both
      procedures. Seventy-seven (43.8%) resected liver metastases were synchronic with
      colorectal tumor. Median disease specific survival (DSS) from first pulmonary
      metastasectomy was 48.9 months, being three and 5-year DSS 65.1% and 41.7%,
      respectively. From CRC-surgery median DSS was 97.2 months, with 3 and 5-year DSS
      rates of 96.7% and 77%, respectively. Five-year DSS from pulmonary metastasectomy
      was 41.7% for patients with combined resection and 52.4% for those without
      hepatic involvement (P=.04). Differences disappeared when considering DSS from
      colorectal surgery. Carcinoembrionary antigen (CEA) before lung surgery over
      10mg/dl and bilateral PM were independent prognostic factors for survival (hazard
      ratio 2.4 and 2.5, respectively). CONCLUSIONS: Patients with resection of PM of
      CRC with history of resected hepatic metastases presented significantly lower
      disease specific survival rates than those undergoing pulmonary metastasectomy
      alone. CEA before lung surgery and bilateral PM associated worse prognosis.

PMID- 29329932
TI  - Development of the Human Fetal Kidney from Mid to Late Gestation in Male and
      Female Infants.
AB  - BACKGROUND: During normal human kidney development, nephrogenesis (the formation
      of nephrons) is complete by term birth, with the majority of nephrons formed late
      in gestation. The aim of this study was to morphologically examine nephrogenesis
      in fetal human kidneys from 20 to 41weeks of gestation. METHODS: Kidney samples
      were obtained at autopsy from 71 infants that died acutely in utero or within 24h
      after birth. Using image analysis, nephrogenic zone width, the number of
      glomerular generations, renal corpuscle cross-sectional area and the cellular
      composition of glomeruli were examined. Kidneys from female and male infants were
      analysed separately. FINDINGS: The number of glomerular generations formed within
      the fetal kidneys was directly proportional to gestational age, body weight and
      kidney weight, with variability between individuals in the ultimate number of
      generations (8 to 12) and in the timing of the cessation of nephrogenesis (still
      ongoing at 37weeks gestation in one infant). There was a slight but significant
      (r2=0.30, P=0.001) increase in renal corpuscle cross-sectional area from mid
      gestation to term in females, but this was not evident in males. The proportions
      of podocytes, endothelial and non-epithelial cells within mature glomeruli were
      stable throughout gestation. INTERPRETATION: These findings highlight spatial and
      temporal variability in nephrogenesis in the developing human kidney, whereas the
      relative cellular composition of glomeruli does not appear to be influenced by
      gestational age.

PMID- 29329935
TI  - Tick-borne pathogen detection: what's new?
AB  - Ticks and the pathogens they transmit constitute a growing burden for human and
      animal health worldwide. Traditionally, tick-borne pathogen detection has been
      carried out using PCR-based methods that rely in known sequences for specific
      primers design. This approach matches with the view of a 'single-pathogen'
      epidemiology. Recent results, however, have stressed the importance of
      coinfections in pathogen ecology and evolution with impact in pathogen
      transmission and disease severity. New approaches, including high-throughput
      technologies, were then used to detect multiple pathogens, but they all need a
      priori information on the pathogens to search. Thus, those approaches are biased,
      limited and conceal the complexity of pathogen ecology. Currently, next
      generation sequencing (NGS) is applied to tick-borne pathogen detection as well
      as to study the interactions between pathogenic and non-pathogenic microorganisms
      associated to ticks, the pathobiome. The use of NGS technologies have surfaced
      two major points: (i) ticks are associated to complex microbial communities and
      (ii) the relation between pathogens and microbiota is bidirectional. Notably, a
      new challenge emerges from NGS experiments, data analysis. Discovering
      associations among a high number of microorganisms is not trivial and therefore
      most current NGS studies report lists of microorganisms without further insights.
      An alternative to this is the combination of NGS with analytical tools such as
      network analysis to unravel the structure of microbial communities associated to
      ticks in different ecosystems.

PMID- 29329936
TI  - Child-onset paroxysmal exercise-induced dystonia as the initial manifestation of
      hereditary Parkinson's disease.

PMID- 29329934
TI  - Application of our understanding of pathogenesis of herpetic stromal keratitis
      for novel therapy.
AB  - HSV-1 ocular infection can cause herpes stromal keratitis (SK), an
      immunopathological lesion. Frequent recurrences can lead to progressive corneal
      scaring which can result in vision impairment if left untreated. Currently, the
      acute and epithelial forms of SK are usually controlled using anti-viral drugs.
      However, chronic forms of SK which are inflammatory in nature, require the
      addition of a topical corticosteroid to the anti-viral treatment regimen. In this
      review, we highlight the essential events involved in SK pathogenesis which can
      be targeted for improved therapy. We also examine some approaches which can be
      combined with the current treatments to effectively control SK.

PMID- 29329937
TI  - Isolated hemifacial spasm presenting as unilateral, involuntary ear movements.

PMID- 29329938
TI  - Pipeline to gene discovery - Analysing familial Parkinsonism in the Queensland
      Parkinson's Project.
AB  - INTRODUCTION: Family based study designs provide an informative resource to
      identify disease-causing mutations. The Queensland Parkinson's Project (QPP) has
      been involved in numerous genetic screening studies; however, details of the
      families enrolled into the register have not been comprehensively reported. This
      article characterises the families enrolled in the QPP and summarises monogenic
      forms of hereditary Parkinsonism found in the register. METHOD: The presence of
      pathogenic point mutations and copy number variations (CNVs) were, generally,
      screened in a sample of over 1000 PD patients from the total of 1725. Whole exome
      sequencing (WES) was performed on eighteen probands from multiplex families.
      RESULTS: The QPP contains seventeen incidences of confirmed monogenic forms of
      PD, including LRRK2 p.G2019S, VPS35 p.D620N, SNCA duplications and PARK2 p.G430D
      (hom) & exon 4 deletion (hom). Of these seventeen, five belong to multi-incident
      families, while another eight have a family history of at least one other case of
      PD. In additional families, WES did not identify known forms of monogenic
      Parkinsonism; however, three heterozygous mutations in PARK2, p.R275W, p.Q34fs,
      and a 40bp deletion in exon 3 were identified. Of these three mutations, only the
      40bp deletion segregated with disease in a dominant inheritance pattern.
      CONCLUSION: Eighteen probands have screened negative for known CNVs and mutations
      that cause clear monogenic forms of PD. Each family is a candidate for further
      genetic analysis to identify genetic variants segregating with disease. The
      families enrolled in the QPP provide a useful resource to aid in identifying
      novel forms of monogenic PD.

PMID- 29329939
TI  - Enhanced mobility of non aqueous phase liquid (NAPL) during drying of wet sand.
AB  - Enhanced upward mobility of a non aqueous phase liquid (NAPL) present in wet sand
      during natural drying, and in the absence of any external pressure gradients, is
      reported for the first time. This mobility was significantly higher than that
      expected from capillary rise. Experiments were performed in a glass column with a
      small layer of NAPL-saturated sand trapped between two layers of water-saturated
      sand. Drying of the wet sand was induced by flow of air across the top surface of
      the wet sand. The upward movement of the NAPL, in the direction of water
      transport, commenced when the drying effect reached the location of the NAPL and
      continued as long as there was significant water evaporation in the vicinity of
      NAPL, indicating a clear correlation between the NAPL rise and water evaporation.
      The magnitude and the rate of NAPL rise was measured at different water
      evaporation rates, different initial locations of the NAPL, different grain size
      of the sand and the type of NAPL (on the basis of different NAPL-glass contact
      angle, viscosity and density). A positive correlation was observed between
      average rate of NAPL rise and the water evaporation while a negative correlation
      was obtained between the average NAPL rise rate and the NAPL properties of
      contact angle, viscosity and density. There was no significant correlation of
      average NAPL rise rate with variation of sand grain size between 0.1 to 0.5mm.
      Based on these observations and on previous studies reported in the literature,
      two possible mechanisms are hypothesized -a) the effect of the spreading
      coefficient resulting in the wetting of NAPL on the water films created and b) a
      moving water film due to evaporation that "drags" the NAPL upwards. The NAPL rise
      reported in this paper has implications in fate and transport of chemicals in
      NAPL contaminated porous media such as soils and exposed dredged sediment
      material, which are subjected to varying water saturation levels due to drying
      and rewetting.

PMID- 29329940
TI  - Cardiovascular Risk Reduction in Persons Living With HIV: Treatment Development,
      Feasibility, and Preliminary Results.
AB  - Persons living with HIV (PLWH) have elevated risks for cardiovascular disease
      (CVD). Our goal was to develop and pilot test a tailored intervention to improve
      CVD risk perception and the adoption of heart-healthy behaviors. In-depth
      qualitative interviews were conducted with 30 PLWH participants to examine
      learning needs and preferences. An intervention manual was developed and tested
      in an open pilot with eight participants. Participants were stable on
      antiretroviral therapy and were recruited from two urban HIV clinics in the
      northeastern United States. Thematic analysis identified five major themes: (a)
      tailored structure and design for PLWH, (b) learning needs (specific to HIV), (c)
      desire for prompts/reminders (to exercise), (d) importance of participant
      resources, and (e) need for personal evaluation and goal setting. Feasibility and
      acceptability of the intervention were demonstrated with high session attendance
      and treatment satisfaction. Further testing is warranted.

PMID- 29329941
TI  - Analysis of refuse-to-file policy for generic drug application in Taiwan.
AB  - Generic drugs are accounted for majority of medicinal products. To reduce the
      unnecessary review for incomplete dossiers of generic drugs, Taiwanese government
      launched a refuse-to-file (RTF) process since 2017. The present study aimed to
      examine the outcome of RTF process by analyzing application characteristic, RTF
      rate and deficiencies found in the submitted dossiers. Descriptive analyses of
      administrative information, chemistry, manufacturing and controls, bioequivalence
      study, and comparative dissolution testing were presented during the first 6
      months after the implementation of RTF policy. The results showed that the source
      of application was likely a determinant to the RTF outcome, i.e., foreign rather
      than domestic applications were more liable to be RTF. It is possibly that (i)
      RTF applications were mainly due to incomplete dossiers regarding bioequivalence
      study and comparative dissolution testing, and (ii) the studies (bioequivalence
      and dissolution) of domestic applications conducted locally are exempted from the
      RTF process because they are allowed to submit for review before generic drug
      applications. Finally, the dossier integrity appeared not improved during the
      period of analysis as the number of RTF did not reduce by month. Results of the
      present study may help pharmaceutical industry to improve the dossiers' quality
      by fixing the deficiencies of generic drug submission.

PMID- 29329942
TI  - Variational neuroethology: Answering further questions: Reply to comments on
      "Answering Schrodinger's question: A free-energy formulation".

PMID- 29329943
TI  - Experience versus diagnosis as the appropriate basis for assessment of
      depression: A reply to the commentary from Kirmayer et al. (2017).

PMID- 29329944
TI  - Use of SuperARMS EGFR Mutation Detection Kit to Detect EGFR in Plasma Cell-free
      DNA of Patients With Lung Adenocarcinoma.
AB  - BACKGROUND: The SuperARMS EGFR Mutation Detection Kit (SuperARMS) is highly
      selective and sensitive and able to detect 41 of the most common somatic
      mutations in exons 18 to 21 of the epidermal growth factor receptor gene (EGFR).
      It allows for the detection of 0.2% to 0.8% mutant DNA in a background of 99.8%
      to 99.2% normal DNA. The present study assessed the performance of SuperARMS in
      detecting EGFR mutations in cell-free DNA (cfDNA) samples derived from plasma in
      patients with advanced lung adenocarcinoma. MATERIALS AND METHODS: A total of 180
      patients with advanced clinical stage lung adenocarcinoma were retrospectively
      registered. The concordance between the EGFR mutations detected by SuperARMS and
      ARMS (AmoyDx EGFR 29 Mutations Detection Kit) was analyzed. RESULTS: Of the 180
      samples, 57 (31.7%) were positive for EGFR mutations using SuperARMS, with 38
      (21.1%) positive using ARMS. For the entire cohort, the positive, negative, and
      overall concordance rates were 97.3% (95% confidence interval [CI], 86.2%-99.5%),
      85.3% (95% CI, 78.6%-90.2%), and 87.8% (95% CI, 82.2%-91.8%), respectively. The
      kappa value was 0.69 (95% CI, 0.57-0.81). For the 61 treatment-naive patients and
      119 previously treated patients, the kappa values were 0.59 (95% CI, 0.37-0.79)
      and 0.74 (95% CI, 0.60-0.87), respectively. SuperARMS identified 9 samples
      harboring the T790M mutation; of these, only 1 (11.1%) was detected using ARMS.
      CONCLUSION: SuperARMS is a promising plasma-based assay for EGFR mutations,
      including T790M. It might be useful in advanced-stage lung adenocarcinoma
      patients whose tissue biopsy samples are insufficient for a traditional
      diagnostic EGFR assay or for patients with a poor performance status.

PMID- 29329945
TI  - Model of acetic acid-affected growth and poly(3-hydroxybutyrate) production by
      Cupriavidus necator DSM 545.
AB  - Acetic acid, a potential growth inhibitor, commonly occurs in lignocellulosic
      hydrolysates. The growth of Cupriavidus necator DSM 545 and production of poly(3
      hydroxybutyrate) (PHB) by this bacterium in a glucose-based medium supplemented
      with various initial concentrations of acetic acid are reported. The bacterium
      could use both glucose and acetic acid to grow and produce PHB, but acetic acid
      inhibited growth once its initial concentration exceeded 0.5 g/L. As acetic acid
      is an unavoidable contaminant in hydrolysates used as sugar sources in commercial
      fermentations, a mathematical model was developed to describe its impact on
      growth and the production of PHB. The model was shown to satisfactorily apply to
      growth and PHB production data obtained in media made with acetic-acid-containing
      hydrolysates of Napier grass and oil palm trunk as carbon substrates.

PMID- 29329946
TI  - A primer on caspase mechanisms.
AB  - Caspases belong to a diverse clan of proteolytic enzymes known as clan CD with
      highly disparate functions in cell signaling. The caspase members of this clan
      are only found in animals, and most of them orchestrate the demise of cells by
      the highly distinct regulated cell death phenotypes known as apoptosis and
      pyroptosis. This review looks at the mechanistic distinctions between the
      activity and activation mechanisms of mammalian caspases compared to other
      members of clan CD. We also compare and contrast the role of different caspase
      family members that program anti-inflammatory and pro-inflammatory cell death
      pathways.

PMID- 29329947
TI  - [Pseudoexfoliation syndrome and pseudoexfoliation glaucoma].
AB  - Pseudoexfoliation syndrome is an age-related systemic disease that mainly affects
      the anterior structures of the eye. Despite a worldwide distribution, reported
      incidence and prevalence of this syndrome vary widely between ethnicities and
      geographical areas. The exfoliative material is composed mainly of abnormal cross
      linked fibrils that accumulate progressively in some organs such as the heart,
      blood vessels, lungs or meninges, and particularly in the anterior structures of
      the eye. The exact pathophysiological process still remains unclear but the
      association of genetic and environmental factors are thought to play a role in
      the development and progressive extracellular accumulation of exfoliative
      material. Hence, LOXL1 gene polymorphisms, responsible for metabolism of some
      components of elastic fibers and extracellular matrix, and increased natural
      exposure to ambient ultraviolet or caffeine consumption have been associated with
      pseudoexfoliation syndrome. Ophthalmological manifestations are commonly
      bilateral with an asymmetric presentation and can lead to severe visual
      impairment and blindness more frequently than in the general population, mainly
      related to glaucoma and cataract. Pseudoexfoliation glaucoma is a major
      complication of pseudoexfoliation syndrome and represents the main cause of
      identifiable glaucoma worldwide. Visual field progression is more rapid than that
      observed in primary open angle glaucoma, and filtering surgery is more frequently
      required. Nuclear cataract is more frequent and occurs earlier than in the
      general population. Owing to poorer pupil dilation and increased zonular
      instability, cataract surgery with pseudoexfoliation is associated with a 5- to
      10-fold increase in surgical complications compared to cataract surgery without
      pseudoexfoliation. Some specific treatments targeting production, formation or
      accumulation of exfoliative material could improve the prognosis of this
      syndrome.

PMID- 29329949
TI  - Running Out of Success in HF Therapy ?

PMID- 29329948
TI  - NKp46 Receptor-Mediated Interferon-gamma Production by Natural Killer Cells
      Increases Fibronectin 1 to Alter Tumor Architecture and Control Metastasis.
AB  - Natural killer (NK) cells are innate lymphoid cells, and their presence within
      human tumors correlates with better prognosis. However, the mechanisms by which
      NK cells control tumors in vivo are unclear. Here, we used reflectance confocal
      microscopy (RCM) imaging in humans and in mice to visualize tumor architecture in
      vivo. We demonstrated that signaling via the NK cell receptor NKp46 (human) and
      Ncr1 (mouse) induced interferon-gamma (IFN-gamma) secretion from intratumoral NK
      cells. NKp46- and Ncr1-mediated IFN-gamma production led to the increased
      expression of the extracellular matrix protein fibronectin 1 (FN1) in the tumors,
      which altered primary tumor architecture and resulted in decreased metastases
      formation. Injection of IFN-gamma into tumor-bearing mice or transgenic
      overexpression of Ncr1 in NK cells in mice resulted in decreased metastasis
      formation. Thus, we have defined a mechanism of NK cell-mediated control of
      metastases in vivo that may help develop NK cell-dependent cancer therapies.

PMID- 29329950
TI  - Dual Vasopressin V1a/V2 Antagonism: The Next Step in Neurohormonal Modulation in
      Patients With Heart Failure?
AB  - Stimulation of the V1a receptor for arginine vasopressin produces myocardial and
      vascular effects similar to those of angiotensin II while stimulation of the V2
      receptor causes fluid retention. There are no data with sustained blockade of the
      V1a receptor while single-dose experiments suggest benefit. Acute and chronic
      administration of selective V2 receptor antagonists reliably relieves dyspnea and
      produces diuresis without adverse effects on renal function or neurohormonal
      stimulation, either as adjunctive or alternative therapy to loop diuretics, but
      has not been shown to improve outcomes as adjunctive therapy. Combined antagonism
      has been tried only in single-dose studies in stable patients or over the short
      term in acute heart failure, with encouraging results. Based on the both the
      pathophysiologic rationale for additional neurohormonal blockade and these
      results, chronically blocking both receptors, particularly in more congested
      patients, may offer significant benefit either as adjunctive or alternative
      therapy to standard diuretics.

PMID- 29329951
TI  - Medical and health risks associated with communicable diseases of Rohingya
      refugees in Bangladesh 2017.
AB  - Complex emergencies remain major threats to human well-being in the 21st century.
      More than 300000 Rohingya people from Myanmar, one of the most forgotten
      minorities globally, have fled to neighboring countries over the past decades. In
      the recent crisis, the sudden influx of Rohingya people over a 3-month period
      almost tripled the accumulated displaced population in Bangladesh. Using the
      Rohingya people in Bangladesh as a case context, this perspective article
      synthesizes evidence in the published literature regarding the possible key
      health risks associated with the five main health and survival supporting
      domains, namely water and sanitation, food and nutrition, shelter and non-food
      items, access to health services, and information, for the displaced living in
      camp settlements in Asia.

PMID- 29329952
TI  - Molecular characterization and expression of complement factor I in Pelteobagrus
      vachellii during Aeromonas hydrophila infection.
AB  - Complement factor I (CFI) is a novel regulatory serine protease that plays an
      important role in resistance to pathogen infection. In this study, the CFI gene
      of Pelteobagrus vachellii (Pv-CFI) was sequenced and characterized. The full
      length cDNA of 2320 bp includes a 155 bp 5'-untranslated region (UTR), a 164 bp
      3'-UTR, and a 2001 bp open reading frame (ORF) encoding a 667 amino acids.
      Multiple sequence alignment revealed five highly conserved domains with a typical
      modular architecture and identical active sites in vertebrates, indicating a
      conserved function. Pv-CFI mRNA was constitutively expressed in all examined
      tissues and most abundant in liver. During infection with Aeromonas hydrophila,
      Pv-CFI mRNA expression was significantly up-regulated in liver at 3-24 h, spleen
      at 3-48 h and head kidney at 3-48 h. The results suggest Pv-CFI plays an
      important role in resistance to pathogenic bacteria in P. vachellii.

PMID- 29329953
TI  - Canine macrophages can like human macrophages be in vitro activated toward the
      M2a subtype relevant in allergy.
AB  - The M2a subtype of macrophages plays an important role in human immunoglobulin E
      (IgE-mediated allergies) and other Th2 type immune reactions. In contrast, very
      little is known about these cells in the dog. Here we describe an in vitro method
      to activate canine histiocytic DH82 cells and primary canine monocyte-derived
      macrophages (MDMs) toward the M2a macrophages using human cytokines. For a side
      by-side comparison, we compared the canine cells to human MDMs, and the human
      monocytic cell line U937 activated towards M1 and M2a cells on the cellular and
      molecular level. In analogy to activated human M2a cells, canine M2a,
      differentiated from both DH82 and MDMs, showed an increase in CD206 surface
      receptor expression compared to M1. Interestingly, canine M2a, but not M1 derived
      from MDM, upregulated the high-affinity IgE receptor (FcepsilonRI). Transcription
      levels of M2a-associated genes (IL10, CCL22, TGFbeta, CD163) showed a diverse
      pattern between the human and dog species, whereas M1 genes (IDO1, CXCL11, IL6,
      TNF-alpha) were similarly upregulated in canine and human M1 cells (cell lines
      and MDMs). We suggest that our novel in vitro method will be suitable in
      comparative allergology studies focussing on macrophages.

PMID- 29329954
TI  - Comparative myology of the ankle of Leopardus wiedii and L. geoffroyi (Carnivora:
      Felidae): functional consistency with osteology, locomotor habits and hunting in
      captivity.
AB  - Leopardus wiedii (margay) is the only arboreal Neotropical felid able to climb
      head-first down trees, due to its ability to rotate its tarsal joint 180 degrees
      . A closely related, similar-sized species, L. geoffroyi (Geoffroy's cat)
      exhibits more typical terrestrial habits and lacks the arboreal capabilities of
      L. wiedii. There is osteological evidence that supports a mechanical
      specialization of L. wiedii's tarsal joint for inversion, but there have been no
      studies on the myology of this specialization. Based on comparative gross-anatomy
      dissections of zeugo- and autopodial muscles related to the ankle joint of one
      margay specimen and two Geoffroys cats, we identified myological specializations
      of L. wiedii that support its arboreal abilities. In addition, we documented both
      species hunting the same prey (domestic pigeon Columba livia, Aves: Columbidae)
      in captivity, to complement. We report differences in the origin, insertion and
      belly in 8 of the 10 dissected muscles. At least 3 of these interspecific
      variations can be associated with strengthening of the main muscles that command
      inversion/eversion movements of the tarsal joint and support the body weight in
      the head-down climbing position typical of L. wiedii. Frame-by-frame video
      reconstructions depict the sequence of movements in these species while hunting
      and highlight the advantages of the arboreal abilities of L. wiedii.

PMID- 29329955
TI  - Longitudinal predictors of early language in infants with Down syndrome: A
      preliminary study.
AB  - PURPOSE: Children with Down syndrome (DS) typically have marked delays in
      language development relative to their general cognitive development, with
      particular difficulties in expressive compared to receptive language. Although
      early social communication skills, including gestures and joint attention, have
      been shown to be related to later language outcomes in DS, knowledge is limited
      as to whether these factors exclusively predict outcomes, or whether other
      factors (e.g. perceptual and non-verbal skills) are involved. This study
      addressed this question. METHOD: Longitudinal data for a group of infants with DS
      (n = 14) and a group of typically-developing (TD) infants (n = 35) were collected
      on measures that have been shown to predict language in TD infants and/or those
      with developmental delays. These included: non-verbal mental ability, speech
      segmentation skills, and early social communication skills (initiating and
      responding to joint attention, initiating behavioural requests). RESULTS: Linear
      regression analyses showed that speech segmentation and initiating joint
      attention were the strongest predictors of later language in the TD group,
      whereas non-verbal mental ability and responding to joint attention were the
      strongest predictors of later language for infants with DS. CONCLUSIONS: Speech
      segmentation ability may not determine language outcomes in DS, and language
      acquisition may be more constrained by social communication and general cognitive
      skills.

PMID- 29329956
TI  - Herd immunity: hyperimmune globulins for the 21st century.

PMID- 29329957
TI  - Safety and tolerability of a novel, polyclonal human anti-MERS coronavirus
      antibody produced from transchromosomic cattle: a phase 1 randomised, double
      blind, single-dose-escalation study.
AB  - BACKGROUND: Middle East respiratory syndrome (MERS) is a severe respiratory
      illness with an overall mortality of 35%. There is no licensed or proven
      treatment. Passive immunotherapy approaches are being developed to prevent and
      treat several human medical conditions where alternative therapeutic options are
      absent. We report the safety of a fully human polyclonal IgG antibody (SAB-301)
      produced from the hyperimmune plasma of transchromosomic cattle immunised with a
      MERS coronavirus vaccine. METHODS: We did a phase 1 double-blind, placebo
      controlled, single-dose escalation trial at the National Institutes of Health
      Clinical Center. We recruited healthy participants aged 18-60 years who had
      normal laboratory parameters at enrolment, a body-mass index of 19-32 kg/m2, and
      a creatinine clearance of 70 mL/min or more, and who did not have any chronic
      medical problems that required daily oral medications, a positive rheumatoid
      factor (>=15 IU/mL), IgA deficiency (<7 mg/dL), or history of allergy to
      intravenous immunoglobulin or human blood products. Participants were randomly
      assigned by a computer-generated table, made by a masked pharmacist, to one of
      six cohorts (containing between three and ten participants each). Cohorts 1 and 2
      had three participants, randomly assigned 2:1 to receive active drug SAB-301
      versus normal saline placebo; cohorts 3 and 4 had six participants randomised
      2:1; and cohorts 5 and 6 had ten participants, randomised 4:1. Participants
      received 1 mg/kg, 2.5 mg/kg, 5 mg/kg, 10 mg/kg, 20 mg/kg, or 50 mg/kg of SAB-301,
      or equivalent volume placebo (saline control), on day 0, and were followed up by
      clinical, laboratory, and pharmacokinetic assessments on days 1, 3, 7, 21, 42,
      and 90. The primary outcome was safety, and immunogenicity was a secondary
      outcome. We analysed the intention-to-treat population. This trial is registered
      with ClinicalTrials.gov, number NCT02788188. FINDINGS: Between June 2, 2016, and
      Jan 4, 2017, we screened 43 participants, of whom 38 were eligible and randomly
      assigned to receive SAB-301 (n=28) or placebo (n=10). 97 adverse events were
      reported: 64 adverse events occurred in 23 (82%) of 28 participants receiving SAB
      301 (mean 2.3 adverse events per participant). 33 adverse events occurred in all
      ten participants receiving placebo (mean 3.3 adverse events per participant). The
      most common adverse events were headache (n=6 [21%] in participants who received
      SAB-301 and n=2 [20%] in those receiving placebo), albuminuria (n=5 [18%] vs n=2
      [20%]), myalgia (n=3 [11%] vs n=1 [10%]), increased creatine kinase (n=3 [11%] vs
      1 [10%]), and common cold (n=3 [11%] vs n=2 [20%]). There was one serious adverse
      event (hospital admission for suicide attempt) in one participant who received 50
      mg/kg of SAB-301. The area under the concentration-time curve (AUC) in the 50
      mg/kg dose (27 498 MUg * days per mL) is comparable to the AUC that was
      associated with efficacy in a preclinical model. INTERPRETATION: Single infusions
      of SAB-301 up to 50 mg/kg appear to be safe and well tolerated in healthy
      participants. Human immunoglobulin derived from transchromosomic cattle could
      offer a new platform technology to produce fully human polyclonal IgG antibodies
      for other medical conditions. FUNDING: National Institute of Allergy and
      Infectious Diseases, National Institutes of Health, and Biomedical Advanced
      Research and Development Authority.

PMID- 29329958
TI  - Contact tracing for the control of infectious disease epidemics: Chronic Wasting
      Disease in deer farms.
AB  - Contact tracing is a crucial component of the control of many infectious
      diseases, but is an arduous and time consuming process. Procedures that increase
      the efficiency of contact tracing increase the chance that effective controls can
      be implemented sooner and thus reduce the magnitude of the epidemic. We
      illustrate a procedure using Graph Theory in the context of infectious disease
      epidemics of farmed animals in which the epidemics are driven mainly by the
      shipment of animals between farms. Specifically, we created a directed graph of
      the recorded shipments of deer between deer farms in Pennsylvania over a
      timeframe and asked how the properties of the graph could be exploited to make
      contact tracing more efficient should Chronic Wasting Disease (a prion disease of
      deer) be discovered in one of the farms. We show that the presence of a large
      strongly connected component in the graph has a significant impact on the number
      of contacts that can arise.

PMID- 29329959
TI  - miR-21 suppression prevents cardiac alterations induced by d-galactose and
      doxorubicin.
AB  - d-galactose (d-gal)-induced cardiac alterations and Doxorubicin (Dox)-induced
      cardiomyocyte senescence are commonly used models to study cardiac aging.
      Accumulating evidence has suggested that microRNAs (miRNAs, miRs) are critically
      involved in the regulation of cellular and organismal aging and age-related
      diseases. However, little has been revealed about the roles of miRNAs in cardiac
      alterations induced by d-gal and Dox. In this study, we used miRNA arrays to
      investigate the dysregulated miRNAs in heart samples from 15month-old versus
      2month-old male C57BL/6 mice and further validated them in d-gal-induced pseudo
      aging mouse model and Dox-induced cardiomyocyte senescence in vitro model. We
      confirmed a significant increase of miR-21 in all these models by quantitative
      reverse transcription polymerase chain reactions. We further demonstrated that
      miR-21 was able to promote Dox-induced cardiomyocyte senescence whereas
      suppression of miR-21 could prevent that, as determined by percentage of beta-gal
      positive cells and gene markers of aging. Phosphatase and tensin homolog (PTEN)
      was identified as a target gene of miR-21, mediating its effect in increasing
      cardiomyocyte senescence. Finally, we found that miR-21 knockout mice were
      resistant to d-gal-induced alterations in aging-markers and cardiac function.
      Collectively, this study provides direct evidence that inhibition of miR-21 is
      protective against d-gal-induced cardiac alterations and Dox-induced
      cardiomyocyte senescence via targeting PTEN. Inhibition of miR-21 might be a
      novel strategy to combat cardiac aging.

PMID- 29329960
TI  - The Future of LGBT Cancer Care: Practice and Research Implications.
AB  - OBJECTIVES: To synthesize state of the knowledge collected in this volume and
      propose future directions for lesbian, gay, bisexual and transgender (LGBT)
      cancer practice, education, research, and advocacy. DATA SOURCES: Current and
      extant literature. CONCLUSION: Health care disparities that are known but not yet
      fully elucidated in the LGBT population carry into the cancer arena.
      Substantially more effort is required in the domains of patient care, nursing
      practice, nursing and patient-facing services provider education, patient
      education, nursing and interprofessional research, governmental commitment,
      professional organization action, and patient advocacy. IMPLICATIONS FOR NURSING
      PRACTICE: Professional nurses are committed to the uniqueness of each individual
      and respect and value the health and well-being of each individual. To that
      commitment, oncology nurses are positioned to advance the research in the field,
      which will help to clarify the issues and concerns related to LGBT cancer,
      address the health care inequities in this important population, and lead to
      improved outcomes for all.

PMID- 29329961
TI  - [Personalised health services: Suggestions for their effective implementation].
AB  - A strategy of customisation, and its subsequent practical implementation as part
      of personalised treatment pathways, is an appropriate approach to increase
      benefits for patients and to strengthen the competitive position of the provider
      of health services. This requires restructuring and/or reorganising measures to
      enable variants within the treatment pathway as a value creation process to be
      adapted to each individual patient and his illness, living conditions and
      preferences. This 'mass customisation' approach allows us to achieve the
      objective of a constructive interconnection of customisation and standardisation
      of health services. Major, rapid progress in information and communication
      technology plays a key part in this process. Focused design tools for mass
      customisation are the integration of patients into the service delivery process
      and the modularisation of processes and organisation. By taking into account the
      specificities of health services as a confidence good these design tools are
      featured and supported by operational and organisational tools in order to
      develop variants. This approach allows for high-quality health services that are
      perfectly tailored to individual patients' needs and, at the same time, delivered
      in an economic way. On this basis, customised approaches for personalised health
      diagnosis and therapy provide patient-focused health services that manage to
      apply the concept of value-based healthcare in a sophisticated and effective
      form.

PMID- 29329962
TI  - Reported contraceptive use in the month of becoming pregnant among U.S. abortion
      patients in 2000 and 2014.
AB  - OBJECTIVES: The objective was to determine whether types of contraceptive methods
      used by abortion patients in the month they became pregnant changed between 2000
      and 2014. STUDY DESIGN: We used secondary data from the 2000 (n=10,015) and 2014
      (8177) Abortion Patient Surveys. Patients were asked which contraceptive methods
      they had last used and when they had stopped or if they were still using them.
      The main outcome variable was type of contraceptive method used in the month the
      pregnancy began. We used bivariate logistic regressions to assess changes in the
      demographic and contraceptive use profiles of abortion patients. RESULTS: In both
      years, slightly more than half of patients reported that they had used a
      contraceptive method in the month they became pregnant, though the decline from
      54% in 2000 to 51% in 2014 was statistically significant (p=.011). The methods
      most commonly reported to have been used in the month the pregnancy began were
      condoms (28% and 24% in 2000 and 2014, p<.001) followed by the pill (14% and 13%,
      p=.12). There was a statistically significant increase in the proportion of
      abortion patients who reported using long-acting reversible methods in the month
      they got pregnant (0.1% in 2000 vs. 1% in 2014, p<.001), and the estimated number
      of abortions attributed to these users was greater in 2014 than in 2000 (9500 vs.
      1800). CONCLUSIONS: Contraceptive use patterns of abortion patients were similar
      in both time periods, and changes in method use mirrored changes in contraceptive
      use among the larger population of women. IMPLICATIONS: Postabortion
      contraception counseling has the potential to help nonusers find methods that
      meet their preferences and to help women better use their current methods.

PMID- 29329963
TI  - Switch to Ticagrelor in critical limb ischemia antiplatelet study (STT-CLIPS).
AB  - OBJECTIVE: To investigate platelet reactivity in patients with critical limb
      ischemia (CLI) after switching from clopidogrel to ticagrelor. BACKGROUND: High
      on-treatment platelet reactivity (HPR) is highly prevalent in patients with CLI
      treated with clopidogrel. The effect of ticagrelor in patients with CLI is not
      known, however. METHODS: We performed P2Y12 platelet receptor inhibition studies
      (VASP and VerifyNow) in 50 patients with CLI. Tests were performed before and 6+/
      1h after daily 75mg clopidogrel dose. Patients were then switched to ticagrelor
      90mg twice daily for two weeks and platelet assays repeated. Patients were
      divided based on VerifyNow P2Y12 reaction units (PRU). Group 1: HPR defined as
      PRU >=208 and Group 2: Appropriate platelet inhibition (API), PRU <208. RESULTS:
      After two weeks of uninterrupted antiplatelet therapy, mean PRU results were 173
      PRU and 71 PRU at baseline (p<0.0001) and 140 PRU and 63 PRU after 6h (p<0.0001)
      for clopidogrel and ticagrelor, respectively. Before daily clopidogrel dose, 36%
      of patients (n=18) demonstrated HPR and after 6h, 30% (n=15). One patient (2%)
      had HPR on ticagrelor. Ninety-four percent of patients with HPR on clopidogrel
      demonstrated appropriate platelet inhibition after switching to ticagrelor and
      all patients with API on clopidogrel remained with API after switching to
      ticagrelor. Six hours after daily dosing, VASP-PRI >50% was found in 42% of
      clopidogrel and 2% of ticagrelor treated patients. CONCLUSIONS: Among patients
      with CLI, ticagrelor achieved greater platelet inhibition than clopidogrel during
      maintenance treatment and at 6h after daily dosing. High on-treatment platelet
      reactivity to clopidogrel in patients with CLI can be overcome by switching to
      ticagrelor.

PMID- 29329964
TI  - Is quality of registry treatment data related to registrar experience and
      workload? A study of Taiwan cancer registry data.
AB  - BACKGROUND: Although cancer treatment information has been collected through the
      Cancer Registry system in Taiwan for more than 10 years, the accuracy of such
      data has never been evaluated. This study examined the accuracy rate between
      registrar experience and on-site chart review for the first course of cancer
      treatment. METHODS: In this retrospective chart review study, 392 randomly
      selected medical records from 14 hospitals were re-abstracted by experienced
      abstractors. The kappa coefficients of accuracy for the abstracting data were
      calculated against the gold standard. Correlations between registrar background
      and workload were then identified through regression analysis. RESULTS: Regarding
      surgery type, low accuracy rates were noted for gastric cancer (84.0%), oral
      cavity cancer (84.6%), and bladder cancer (88.9%). For chemotherapy, low accuracy
      rates were observed for hematopoietic diseases (81.3%) and esophageal cancer
      (88.0%). For radiotherapy, low accuracy rates were noted for esophageal cancer
      (80.0%), cervical cancer (81.8%), and lymphoma (85.7%). When stratifying by
      surgery type after adjustment for hospital caseload, a high accuracy rate was
      found for cancer registrars who had progressed from basic to advanced licenses
      within 5 years of graduating. CONCLUSION: The accuracy rate for the first course
      of cancer treatment was affected by the cancer type and the experience of cancer
      registrars, but it was not affected by the workload of cancer registrars. We
      recommend that cancer registrars with basic licenses upgrade to advanced licenses
      as soon as possible. Medical record collaboration should establish documentation
      for checklist of radiotherapy and surgical operation records.

PMID- 29329965
TI  - Migration of inferior vena cava filter during the surgery of tibial shaft
      fracture: A case report.

PMID- 29329966
TI  - [Overview of the knowledge and attitudes of physicians in Brazzaville on
      obstructive sleep apnea syndrome].
AB  - INTRODUCTION: Obstructive sleep apnea syndrome (OSAS) is the leading sleep
      related breathing disorder. Its complications and its repercussions on the
      quality of life of patients make the OSAS a real public health problem. The
      objective of this study is to both asses physicians knowledge of OSAS and
      describe their attitudes towards suspect subjects in Brazzaville. MATERIAL AND
      METHOD: This was a cross-sectional study of 230 doctors practicing in various
      hospitals in the city of Brazzaville. The data collection was done by a self
      questionnaire developed after a bibliographic analysis on the OSAS. The
      questionnaire was completed without recourse to a source of information. RESULTS:
      Our sample consisted of 141 (70.50%) general practitioners and 59 (29.50%)
      specialist physicians. The average of the knowledge score was 9.34 points+/-3.03
      points. The general level of physician knowledge about SAS was good in 2% of
      cases, average in 44% of cases and low in 54% of cases. The level of knowledge
      was related to the number of times the OSAS diagnosis was mentioned by the
      physician in his practice (P<0.001), to the doctor's grade (P=0.003); to his
      university of origin and to the quantity of sources of information. When faced
      with suspects OSAS subjects, the doctor, the doctor directed the patient in 62%
      of the cases in ENT and in 49% in the pulmonology. CONCLUSION: The knowledge of
      the doctors on the OSAS are weak; this results in poor management of this
      pathology in the Congo.

PMID- 29329967
TI  - [Prevalence of HIV-Tuberculosis co-infection and HIV impact on patients with
      tuberculosis in the Lubumbashi Health Zone from 2014 to 2015].
AB  - BACKGROUND: Tuberculosis and HIV/AIDS are a dangerous couple in sub-Saharan
      Africa. The aim of this paper is to evaluate the prevalence of the co-infection
      tuberculosis/HIV/AIDS and its impact on issues of tuberculosis patients treated
      in Lubumbashi Heath Zone (LHZ). MATERIALS AND METHODS: A retrospective and
      transversal study was conducted through the analysis of tuberculosis patients'
      data admitted in the tuberculosis Health Centers for Diagnosis and treatment
      (HCDT) in the LHZ from January 2014 to December 2015. TB-HIV co-infection cases
      will be identified and the outcome will be analyzed. RESULTS: Data of 1368
      patients were noted from three HCDT of the TB of the Lubumbashi ZS and among them
      334 cases of co-infections were recorded. The most incriminated age range is 40
      50 years. The mean of age of our patients is 32.84+/-15.32 years and the
      man/women sex ratio is 1.70. The most predominant clinical tuberculosis form is
      the extra pulmonary [EPT (52.70 %)]. Among co-infected patients, the predominant
      form is pulmonary (TPM-). Out of the 51 cases of deaths recorded, 23 (45.10 %)
      also had HIV while 28 (54.90 %) were HIV-negative. There was an increase of 11.6
      % in TB-HIV/AIDS co-infection from 2014 to 2015. CONCLUSION: TB-HIV/AIDS co
      infection is a reality in the LHZ, especially in patients with negative bacterial
      TB (TPM-) and we have to pay a particular attention on the impact of HIV on the
      death of tuberculosis patients.

PMID- 29329968
TI  - Reexamining unconscious response priming: A liminal-prime paradigm.
AB  - Research on the limits of unconscious processing typically relies on the
      subliminal-prime paradigm. However, this paradigm is limited in the issues it can
      address. Here, we examined the implications of using the liminal-prime paradigm,
      which allows comparing unconscious and conscious priming with constant
      stimulation. We adapted an iconic demonstration of unconscious response priming
      to the liminal-prime paradigm. On the one hand, temporal attention allocated to
      the prime and its relevance to the task increased the magnitude of response
      priming. On the other hand, the longer RTs associated with the dual task inherent
      to the paradigm resulted in response priming being underestimated, because
      unconscious priming effects were shorter-lived than conscious-priming effects.
      Nevertheless, when the impact of long RTs was alleviated by considering the
      fastest trials or by imposing a response deadline, conscious response priming
      remained considerably larger than unconscious response priming. These findings
      suggest that conscious perception strongly modulates response priming.

PMID- 29329969
TI  - Inattentional blindness on the full-attention trial: Are we throwing out the baby
      with the bathwater?
AB  - When attention is otherwise engaged, observers may experience inattentional
      blindness, failing to notice objects or events that are presented in plain sight.
      In an inattentional blindness experiment, an unexpectedstimulus ispresented
      alongside primary-task stimuli, and its detection is probed. We evaluate a
      criterion that is commonly used to exclude observers from the data analysis. On
      the final experimental trial, observers do not perform the primary task, but
      instead look for anything new. Observers who fail to report the unexpected
      stimulus on thisfull-attention trialare excluded. On the basis of 4 hypothetical
      experiments and a review of 128 actual experiments from the literature, we
      demonstrate some potentially problematic consequences of implementing the full
      attention-trial exclusion criterion. Excluded observers may cluster in
      experimental conditions and the exclusion criterion may lead researchers to
      understate the pervasiveness of inattentional blindness. It may even render
      usblindto inattentional blindness on the full-attention trial.

PMID- 29329970
TI  - A prospective study on the association of sleep duration with grip strength among
      middle-aged and older Chinese.
AB  - BACKGROUND: Longitudinal studies on sleep duration and grip strength decline are
      limited. This study aimed to evaluate the associations of baseline sleep duration
      with follow-up grip strength and grip strength changeover time among a large
      sample of middle-aged and older Chinese. METHODS: Data from China Health and
      Retirement Longitudinal Study, CHARLS (2011-2015), were analyzed. Hand grip
      strength was measured by dynamometers twice with 4 years interval. Baseline self
      reported nighttime sleep duration was collected by questionnaire. Basic
      demographics, life habits and health status were considered as potential
      confounders. Multivariate linear regression models with quadratic function and
      mixed-effects regression models were fitted. RESULTS: Inverted U-shaped
      associations occurred between baseline sleep duration and follow-up grip strength
      for both males (betalinear = 1.011, plinear = 0.002; betaquadratic = -0.061,
      pquadratic = 0.014) and females (betalinear = 0.605, plinear = 0.005,
      betaquadratic = -0.041, pquadratic = 0.019). Compared to the sleep duration of 7
      h, significant interactions of <5 hours-by-time (gamma= - 0.966 with SEE = 0.442,
      p = .029) in males as well as 5-7 hours-by-time (gamma= - 0.717 with SEE = 0.294,
      p = .015), 7-9 hours-by-time (gamma= - 0.632 with SEE = 0.311, p = .042) and >9
      hours-by-time (gamma= - 1.567 with SEE = 0.560, p = .005) in females were found.
      CONCLUSION: For both males and females, compared to the intermediate sleep
      duration, shorter or longer sleep may predict the weaker follow-up grip strength
      and the faster rate of hand grip strength decline over time.

PMID- 29329971
TI  - Muscle quality is associated with dynamic balance, fear of falling, and falls in
      older women.

PMID- 29329972
TI  - Enhanced production of lactate-based polyesters in Escherichia coli from a
      mixture of glucose and xylose by Mlc-mediated catabolite derepression.
AB  - Lignocellulose-utilizing biorefinery is a promising strategy for the sustainable
      production of value-added products such as bio-based polymers. Simultaneous
      consumption of glucose and xylose in Escherichia coli was achieved by
      overexpression of the gene encoding Mlc, a multiple regulator of glucose and
      xylose uptake. This catabolite derepression gave the enhancement in the
      production of poly (15 mol% lactate-co-3-hydroxybutyrate), up to 65% from 50%
      (wild-type strain) in the cellular contents, of the Mlc-overexpressing strain of
      E. coli on a mixture of glucose and xylose as carbon sources. Microscopic
      analysis indicated that the Mlc-overexpressing strain showed the enlargement of
      cell volume in the presence and absence of polymer production, consequently
      making an expanded volumetric space available for enhanced polymer accumulation.
      The enhanced polymer production by the catabolite derepression was also
      reproducible using the biomass, Miscanthus*giganteus (hybrid Miscanthus), which
      was cultivated in the farm of Hokkaido University.

PMID- 29329974
TI  - Bariatric surgery: many benefits, but emerging risks.

PMID- 29329973
TI  - Altered gene expression in tree shrew retina and retinal pigment epithelium
      produced by short periods of minus-lens wear.
AB  - Hyperopic refractive error is detected by retinal neurons, which generate GO
      signals through a direct emmetropization signaling cascade: retinal pigment
      epithelium (RPE) into choroid and then into sclera, thereby increasing axial
      elongation. To examine signaling early in this cascade, we measured gene
      expression in the retina and RPE after short exposure to hyperopia produced by
      minus-lens wear. Gene expression in each tissue was compared with gene expression
      in combined retina + RPE. Starting 24 days after normal eye opening, three groups
      of juvenile tree shrews (n = 7 each) wore a monocular -5 D lens. The untreated
      fellow eye served as a control. The "6h" group wore the lens for 6 h; the "24h"
      group wore the lens for 24 h; each group provided separate retina and RPE
      tissues. Group "24hC" wore the lens for 24 h and provided combined retina + RPE
      tissue. Quantitative PCR was used to measure the relative differences (treated
      eye vs. control eye) in mRNA levels for 66 candidate genes. In the retina after 6
      h, mRNA levels for seven genes were significantly regulated: EGR1 and FOS (early
      intermediate genes) were down-regulated in the treated eyes. Genes with secreted
      protein products, BMP2 and CTGF, were down-regulated, whilst FGF10, IL18, and SST
      were up-regulated. After 24 h the pattern changed; only one of the seven genes
      still showed differential expression; BMP2 was still down-regulated. Two new
      genes with secreted protein products, IGF2 and VIP, were up-regulated. In the
      RPE, consistent with its role in receiving, processing, and transmitting GO
      signaling, differential expression was found for genes whose protein products are
      at the cell surface, intracellular, in the nucleus, and are secreted. After 6 h,
      mRNA levels for 17 genes were down-regulated in the treated eyes, whilst four
      genes (GJA1, IGF2R, LRP2, and IL18) were up-regulated. After 24 h the pattern was
      similar; mRNA levels for 14 of the same genes were still down-regulated; only
      LRP2 remained up-regulated. mRNA levels for six genes no longer showed
      differential expression, whilst nine genes, not differentially expressed at 6 h,
      now showed differential expression. In the combined retina + RPE after 24 h, mRNA
      levels for only seven genes were differentially regulated despite the
      differential expression of many genes in the RPE. Four genes showed the same
      expression in combined tissue as in retina alone, including up-regulation of VIP
      despite significant VIP down-regulation in RPE. Thus, hyperopia-induced GO
      signaling, as measured by differential gene expression, differs in the retina and
      the RPE. Retinal gene expression changed between 6 h and 24 h of treatment,
      suggesting evolution of the retinal response. Gene expression in the RPE was
      similar at both time points, suggesting sustained signaling. The combined retina
      + RPE does not accurately represent gene expression in either retina or,
      especially, RPE. When gene expression signatures were compared with those in
      choroid and sclera, GO signaling, as encoded by differential gene expression,
      differs in each compartment of the direct emmetropization signaling cascade.

PMID- 29329976
TI  - Therapeutic potential of spinal GLP-1 receptor signaling.
AB  - GLP-1 signaling pathway has been well studied for its role in regulating glucose
      homeostasis, as well as its beneficial effects in energy and nutrient metabolism.
      A number of drugs based on GLP-1 have been used to treat type 2 diabetes
      mellitus. GLP-1R is expressed in multiple organs and numerous experimental
      studies have demonstrated that GLP-1 signaling pathway exhibits pro-survival
      functions in various disorders. In the central nervous system, stimulation of GLP
      1R produces neuroprotective effects in specific neurodegenerative disorders, such
      as Alzheimer's disease and Parkinson's disease. The preproglucagon neurons
      located in the brainstem can also produce GLP-1. GLP-1 analogs have a long-acting
      effect and are able to pass the blood-brain barrier, which probably extends the
      therapeutic efficacy of GLP-1R activation. Neurodegenerative or traumatic
      conditions can damage the spinal cord and result in motor and sensory
      dysfunction. Evidence supports that GLP-1R activation in the spinal cord
      possesses beneficial effects and significant therapeutic potential. Herein, we
      review studies that have focused on GLP-1 and the spinal cord, and summarize the
      expression of GLP-1R and the innervation of PPG neurons in the spinal cord, as
      well as the potential therapeutic benefits of GLP-1R activation.

PMID- 29329977
TI  - Recent insights in the use of nanocarriers for the oral delivery of bioactive
      proteins and peptides.
AB  - Bioactive proteins and peptides have been used with either prophylactic or
      therapeutic purposes, presenting inherent advantages as high specificity and
      biocompatibility. Nanocarriers play an important role in the stabilization of
      proteins and peptides, offering enhanced buccal permeation and protection while
      crossing the gastrointestinal tract. Moreover, preparation of nanoparticles as
      oral delivery systems for proteins/peptides may include tailored formulation
      along with functionalization aiming bioavailability enhancement of carried
      proteins or peptides. Oral delivery systems, namely buccal delivery systems,
      represent an interesting alternative route to parenteric delivery systems to
      carry proteins and peptides, resulting in higher comfort of administration and,
      therefore, compliance to treatment. This paper outlines an extensive overview of
      the existing publications on proteins/peptides oral nanocarriers delivery
      systems, with special focus on buccal route. Manufacturing aspects of most
      commonly used nanoparticles for oral delivery (e.g. polymeric nanoparticles using
      synthetic or natural polymers and lipid nanoparticles) advantages and limitations
      and potential applications of nanoparticles as proteins/peptides delivery systems
      will also be thoroughly addressed.

PMID- 29329975
TI  - Risk of suicide and non-fatal self-harm after bariatric surgery: results from two
      matched cohort studies.
AB  - BACKGROUND: Bariatric surgery reduces mortality, but might have adverse effects
      on mental health. We assessed the risk of suicide and self-harm after bariatric
      surgery compared with non-surgical obesity treatment. METHODS: Suicide and non
      fatal self-harm events retrieved from nationwide Swedish registers were examined
      in two cohorts. The non-randomised, prospective Swedish Obese Subjects (SOS)
      study compared bariatric surgery (n=2010; 1369 vertical-banded gastroplasty, 376
      gastric banding, and 265 gastric bypass) with usual care (n=2037; recruitment
      1987-2001). The second cohort consisted of individuals from the Scandinavian
      Obesity Surgery Registry (SOReg; n=20 256 patients who had gastric bypass)
      matched to individuals treated with intensive lifestyle modification (n=16 162;
      intervention 2006-13) on baseline BMI, age, sex, education level, diabetes,
      cardiovascular disease, history of self-harm, substance misuse, antidepressant
      use, anxiolytics use, and psychiatric health-care contacts. FINDINGS: During 68
      528 person-years (median 18; IQR 14-21) in the SOS study, suicides or non-fatal
      self-harm events were higher in the surgery group (n=87) than in the control
      group (n=49; adjusted hazard ratio [aHR] 1.78, 95% CI 1.23-2.57; p=0.0021); of
      these events, nine and three were suicides, respectively (3.06, 0.79-11.88;
      p=0.11). In analyses by primary procedure type, increased risk of suicide or non
      fatal self-harm was identified for gastric bypass (3.48, 1.65-7.31; p=0.0010),
      gastric banding (2.43, 1.23-4.82; p=0.011), and vertical-banded gastroplasty
      (2.25, 1.37-3.71; p=0.0015) compared with controls. Out of nine deaths by suicide
      in the SOS surgery group, five occurred after gastric bypass (two primary and
      three converted procedures). During 149 582 person-years (median 3.9; IQR 2.8
      5.2), more suicides or non-fatal self-harm events were reported in the SOReg
      gastric bypass group (n=341) than in the intensive lifestyle group (n=84; aHR
      3.16, 2.46-4.06; p<0.0001); of these events, 33 and five were suicides,
      respectively (5.17, 1.86-14.37; p=0.0017). In SOS, substance misuse during follow
      up was recorded in 48% (39/81) of patients treated with surgery and 28% (13/47)
      of controls with non-fatal self-harm events (p=0.023). Correspondingly, substance
      misuse during follow-up was recorded in 51% (162/316) of participants in the
      SOReg gastric bypass group and 29% (23/80) of participants in the intensive
      lifestyle group with non-fatal self-harm events (p=0.0003). The risk of suicide
      and self-harm was not associated with poor weight loss outcome. INTERPRETATION:
      Bariatric surgery was associated with suicide and non-fatal self-harm. However,
      the absolute risks were low and do not justify a general discouragement of
      bariatric surgery. The findings indicate a need for thorough preoperative
      psychiatric history assessment along with provision of information about
      increased risk of self-harm following surgery. Moreover, the findings call for
      postoperative surveillance with particular attention to mental health. FUNDING:
      US National Institutes of Health and Swedish Research Council.

PMID- 29329978
TI  - Data quality over data quantity in computational cognitive neuroscience.
AB  - We analyzed factors that may hamper the advancement of computational cognitive
      neuroscience (CCN). These factors include a particular statistical mindset, which
      paves the way for the dominance of statistical power theory and a preoccupation
      with statistical replicability in the behavioral and neural sciences. Exclusive
      statistical concerns about sampling error occur at the cost of an inadequate
      representation of the problem of measurement error. We contrasted the
      manipulation of data quantity (sampling error, by varying the number of subjects)
      against the manipulation of data quality (measurement error, by varying the
      number of data per subject) in a simulated Bayesian model identifiability study.
      The results were clear-cut in showing that - across all levels of signal-to-noise
      ratios - varying the number of subjects was completely inconsequential, whereas
      the number of data per subject exerted massive effects on model identifiability.
      These results emphasize data quality over data quantity, and they call for the
      integration of statistics and measurement theory.

PMID- 29329979
TI  - How acute stress may enhance subsequent memory for threat stimuli outside the
      focus of attention: DLPFC-amygdala decoupling.
AB  - Stress-related disorders, e.g., anxiety and depression, are characterized by
      decreased top-down control for distracting information, as well as a memory bias
      for threatening information. However, it is unclear how acute stress biases
      mnemonic encoding and leads to prioritized storage of threat-related information
      even if outside the focus of attention. In the current study, healthy adults (N =
      53, all male) were randomly assigned to stress induction using the socially
      evaluated cold-pressor test (SECPT) or a control condition. Participants
      performed a task in which they were required to identify a target letter within a
      string of letters that were either identical to the target and thereby
      facilitating detection (low distractor load) or mixed with other letters to
      complicate the search (high load). Either a fearful or neutral face was presented
      on the background, outside the focus of attention. Twenty-four hours later,
      participants were asked to perform a surprise recognition memory test for those
      background faces. Stress induction resulted in increased cortisol and negative
      subjective mood ratings. Stress did not affect visual search performance,
      however, participants in the stress group showed stronger memory compared to the
      control group for fearful faces in the low attentional load condition.
      Critically, the stress induced memory bias was accompanied by decoupling between
      amygdala and DLFPC during encoding, which may represent a mechanism for decreased
      ability to filter task-irrelevant threatening background information. The current
      study provides a potential neural account for how stress can produce a negative
      memory bias for threatening information even if presented outside the focus of
      attention. Despite of an adaptive advantage for survival, such tendencies may
      ultimately also lead to generalized fear, a possibility requiring additional
      investigation.

PMID- 29329980
TI  - A mass spectrometry imaging approach for investigating how drug-drug interactions
      influence drug blood-brain barrier permeability.
AB  - There is a high need to develop quantitative imaging methods capable of providing
      detailed brain localization information of several molecular species
      simultaneously. In addition, extensive information on the effect of the blood
      brain barrier on the penetration, distribution and efficacy of neuroactive
      compounds is required. Thus, we have developed a mass spectrometry imaging method
      to visualize and quantify the brain distribution of drugs with varying blood
      brain barrier permeability. With this approach, we were able to determine blood
      brain barrier transport of different drugs and define the drug distribution in
      very small brain structures (e.g., choroid plexus) due to the high spatial
      resolution provided. Simultaneously, we investigated the effect of drug-drug
      interactions by inhibiting the membrane transporter multidrug resistance 1
      protein. We propose that the described approach can serve as a valuable
      analytical tool during the development of neuroactive drugs, as it can provide
      physiologically relevant information often neglected by traditional imaging
      technologies.

PMID- 29329981
TI  - Molecular cloning and characterization of leucine aminopeptidase gene from Taenia
      pisiformis.
AB  - Leucine aminopeptidase (LAP, EC: 3.4.11.1) is an important metalloexopeptidase
      that catalyze the hydrolysis of amino-terminal leucine residues from polypeptides
      and proteins. In this study, a full length of cDNA encoding leucine
      aminopeptidase of Taenia pisiformis (TpLAP) was cloned by rapid amplification of
      cDNA-ends using the polymerase chain reaction (RACE-PCR) method. The full-length
      cDNA of the TpLAP gene is 1823 bp and contains a 1569 bp ORF encoding 533 amino
      acids with a putative mass of 56.4 kDa. TpLAP contains two characteristic motifs
      of the M17LAP family in the C-terminal sequence: the metal binding site 265
      [VGKG]-271 and the catalytic domain motif 351-[NTDAEGRL]-357. The soluble GST
      TpLAP protein was expressed in Escherichia coli Transetta (DE3) and four specific
      anti-TpLAP monoclonal antibodies (mAbs) were prepared. In enzymatic assays, the
      optimal activity was observed at pH 9.5 at 45  degrees C. GST-TpLAP displayed a
      hydrolyzing activity for the Leu-pNA substrate with a maximum activity of 46
      U/ml. The enzymatic activity was significantly enhanced by Mn2+ and completely
      inhibited by 20 nM bestatin and 0.15 mM EDTA. The native TpLAP was detected
      specifically in ES components of adult T. pisiformis by western blotting using
      anti-TpLAP mAb as a probe. Quantitative real-time PCR revealed that the TpLAP
      gene was expressed at a high level in adult worm tissues, especially in the
      gravid proglottids (50.71-fold). Immunolocalization analysis showed that TpLAP
      was located primarily in the subtegumental parenchyma zone and the uterine wall
      of adult worms. Our results indicate that TpLAP is a new member of the M17LAP
      family and can be considered as a stage-differentially expressed protein. These
      findings might provide new insights into the study of the mechanisms of growth,
      development and survival of T. pisiformis in the final host and have potential
      value as an attractive target for drug therapy or vaccine intervention.

PMID- 29329982
TI  - Gongylonema pulchrum infection in the human oral cavity: A case report and
      literature review.
AB  - Gongylonema infection is a zoonotic disease occurring throughout the world and is
      mainly caused by consumption of contaminated water and raw food. Adult
      Gongylonema worms can exist as parasites in the human body for up to 10 years and
      cause symptoms of local irritation in the oral cavity, esophagus, and pharynx.
      Herein, we report a rare case in which live Gongylonema pulchrum was detected and
      extracted from the oral cavity of a woman. The pathogen was confirmed as G.
      pulchrum on the basis of microscopic examination and morphologic analysis. The
      patient's symptoms resolved immediately after surgical removal of the parasite,
      and the patient has been advised not to drink water that has not been boiled and
      to avoid consuming unwashed raw vegetables.

PMID- 29329984
TI  - Infralimbic dopamine D2 receptors mediate glucocorticoid-induced facilitation of
      auditory fear memory extinction in rats.
AB  - The infralimbic (IL) cortex of the medial prefrontal cortex plays an important
      role in the extinction of fear memory. Also, it has been showed that both brain
      glucocorticoid and dopamine receptors are involved in many processes such as fear
      extinction that drive learning and memory; however, the interaction of these
      receptors in the IL cortex remains unclear. We examined a putative interaction
      between the effects of glucocorticoid and dopamine receptors stimulation in the
      IL cortex on fear memory extinction in an auditory fear conditioning paradigm in
      male rats. Corticosterone (the endogenous glucocorticoid receptor ligand), or
      RU38486 (the synthetic glucocorticoid receptor antagonist) microinfusion into the
      IL cortex 10 min before test 1 attenuated auditory fear expression at tests 1-3,
      suggesting as an enhancement of fear extinction. The effect of corticosterone,
      but not RU38486 was counteracted by the dopamine D2 receptor antagonist sulpiride
      pre-treatment administered into the IL (at a dose that failed to alter freezing
      behavior on its own). In contrast, intra-IL infusion of the dopamine D1 receptor
      antagonist SCH23390 pre-treatment failed to alter freezing behavior. These
      findings provide evidence for the involvement of the IL cortex D2 receptors in
      CORT-induced facilitation of fear memory extinction.

PMID- 29329983
TI  - Attenuation of noise-induced hyperactivity in the dorsal cochlear nucleus by pre
      treatment with MK-801.
AB  - It has previously been hypothesized that hyperactivity of central auditory
      neurons following exposure to intense noise is a consequence of synaptic
      alterations. Recent studies suggest the involvement of NMDA receptors in the
      induction of this hyperactive state. NMDA receptors can mediate long term changes
      in the excitability of neurons through their involvement in excitotoxic injury
      and long term potentiation and depression. In this study, we examined the effect
      of administering an NMDA receptor blocker on the induction of hyperactivity in
      the dorsal cochlear nucleus (DCN) following intense sound exposure. Our
      prediction was that if hyperactivity induced by intense sound exposure is
      dependent on NMDA receptors, then blocking these receptors by administering an
      NMDA receptor antagonist just before animals are exposed to intense sound should
      reduce the degree of hyperactivity that subsequently emerges. We compared the
      levels of hyperactivity that develop in the DCN after intense sound exposure to
      activity recorded in control animals that were not sound exposed. One group of
      animals to be sound exposed received intraperitoneal injection of MK-801 twenty
      minutes preceding the sound exposure, while the other group received injection of
      saline. Recordings performed in the DCN 26-28 days post-exposure revealed
      increased response thresholds and widespread increases in spontaneous activity in
      the saline-treated animals that had been sound exposed, consistent with earlier
      studies. The animals treated with MK-801 preceding sound exposure showed
      similarly elevated thresholds but an attenuation of hyperactivity in the DCN; the
      attenuation was most robust in the high frequency half of the DCN, but lower
      levels of hyperactivity were also found in the low frequency half. These findings
      suggest that NMDA receptors are an important component of the hyperactivity
      inducing mechanism following intense sound exposure. They further suggest that
      blockade of NMDA receptors may offer a useful therapeutic approach to preventing
      induction of noise-induced hyperactivity-related hearing disorders, such as
      tinnitus and hyperacusis.

PMID- 29329985
TI  - The scavenger activity of the human P2X7 receptor differs from P2X7 pore function
      by insensitivity to antagonists, genetic variation and sodium concentration:
      Relevance to inflammatory brain diseases.
AB  - Activation of P2X7 receptors is widely recognised to initiate proinflammatory
      responses. However P2X7 also has a dual function as a scavenger receptor which is
      active in the absence of ATP and plasma proteins and may be important in central
      nervous system (CNS) diseases. Here, we investigated both P2X7 pore formation and
      its phagocytic function in fresh human monocytes (as a model of microglia) by
      measuring ATP-induced ethidium dye uptake and fluorescent bead uptake
      respectively. This was studied in monocytes expressing various polymorphic
      variants as well as in the presence of different P2X7 antagonists and ionic
      media. P2X7-mediated phagocytosis was found to account for about half of
      Latrunculin (or Cytochalasin D)-sensitive bead engulfment by fresh human
      monocytes. Monocytes harbouring P2X7 Ala348Thr or Glu496Ala polymorphic variants
      showed increase or loss of ethidium uptake respectively, but these changes in
      pore formation did not always correspond to the changes in phagocytosis of YG
      beads. Unlike pore function, P2X7-mediated phagocytosis was not affected by three
      potent selective P2X7 antagonists and remained identical in Na+ and K+ media.
      Taken together, our results show that P2X7 is a scavenger receptor with important
      function in the CNS but its phagocytic function has features distinct from its
      pore function. Both P2X7 pore formation and P2X7-mediated phagocytosis should be
      considered in the design of new P2X7 antagonists for the treatment of CNS
      diseases.

PMID- 29329986
TI  - Prospects in non-invasive assessment of liver fibrosis: Liquid biopsy as the
      future gold standard?
AB  - Liver fibrosis is the result of persistent liver injury, and is characterized by
      sustained scar formation and disruption of the normal liver architecture. The
      extent of fibrosis is considered as an important prognostic factor for the
      patient outcome, as an absence of (early) treatment can lead to the development
      of liver cirrhosis and hepatocellular carcinoma. Till date, the most sensitive
      and specific way for the diagnosis and staging of liver fibrosis remains liver
      biopsy, an invasive diagnostic tool, which is associated with high costs and
      discomfort for the patient. Over time, non-invasive scoring systems have been
      developed, of which the measurements of serum markers and liver stiffness are
      validated for use in the clinic. These tools lack however the sensitivity and
      specificity to detect small changes in the progression or regression of both
      early and late stages of fibrosis. Novel non-invasive diagnostic markers with the
      potential to overcome these limitations have been developed, but often lack
      validation in large patient cohorts. In this review, we will summarize novel
      trends in non-invasive markers of liver fibrosis development and will discuss
      their (dis-)advantages for use in the clinic.

PMID- 29329987
TI  - Quantitative proteomics in Friedreich's ataxia B-lymphocytes: A valuable approach
      to decipher the biochemical events responsible for pathogenesis.
AB  - Friedreich's ataxia (FRDA) represents the most frequent type of autosomal
      recessively inherited ataxia and is caused by the deficiency of frataxin, a
      mitochondrial protein. It is known that frataxin-deficiency leads to alterations
      in cellular and mitochondrial iron metabolism and impacts in the cell physiology
      at several levels. Frataxin is thought to play a role in iron-sulfur cluster
      biogenesis and heme synthesis. Currently, cellular antioxidant defense is
      dysregulated when frataxin is deficient, which exacerbates oxidative damage in
      FRDA. Moreover, alterations in lipid metabolism have been observed in several
      models of the disease. To better understand the biochemical sequelae of frataxin
      reduction, global protein expression analysis was performed using quantitative
      proteomic experiments in Friedreich's ataxia patient-derived B-lymphocytes as
      compared to controls. We were able to confirm a subset of changes in these cells
      and importantly, we observed previously unreported signatures of protein
      expression. Among the novel protein signatures that we have identified, the
      decrease in CHCHD4 might partly explain some aspects of the molecular
      pathogenesis of FRDA. The identification of a core set of proteins changing in
      the FRDA pathogenesis is a useful tool in trying to decipher the function(s) of
      frataxin in order to clarify the mitochondrial metabolic disease process.

PMID- 29329989
TI  - Reassessment of Right Middle Lobe Lung Cancer: Comparison of Segments 4 and 5
      Tumors.
AB  - BACKGROUND: The purpose of this study was to elucidate the clinical behavior of
      right middle lobe lung cancer, with focus on the tumor location. METHODS: We
      reviewed retrospectively 711 patients who underwent lobectomy or bilobectomy for
      clinical stage I non-small cell lung cancer (upper lobe, 346; middle lobe, 82;
      lower lobe, 283). Factors affecting survival were assessed by log rank tests and
      Cox regression analyses. RESULTS: The prognosis of patients with segment 5 tumors
      (n = 39) was significantly worse than that of patients with segment 4 tumors (n =
      43; 5-year overall survival rates, 69.8% versus 87.6%, p = 0.040; and 5-year
      recurrence-free survival rates, 58.4% versus 73.0%, p = 0.029). Segment 5 tumors
      were an independent factor for poor prognosis in multivariable Cox regression
      analysis, and tended to cause more pathologic mediastinal lymph node metastases
      than segment 4 tumors (12.8% versus 2.3%, p = 0.097). Compared with tumors in the
      other lobes, patients with segment 4 tumors demonstrated no significant
      difference in prognosis; however, patients with segment 5 tumors demonstrated a
      significantly and outstandingly worse prognosis than patients with other lobe
      tumors (5-year overall survival rates, 69.8% versus 82.2%, p = 0.020; and 5-year
      recurrence-free survival rates, 58.4% versus 71.4%, p = 0.0071). CONCLUSIONS:
      Patients with segment 5 tumors had a worse prognosis than patients with segment 4
      and other lobe tumors. We speculate that is because segment 5 tumors cause more
      metastases to the mediastinal lymph nodes. Tumor location was an important
      prognostic factor for patients with right middle lobe lung cancer.

PMID- 29329988
TI  - Rethinking Medicaid Coverage and Payment Policy to Promote High Value Care: The
      Case of Long-Acting Reversible Contraception.
AB  - CONTEXT: Long-acting reversible contraception (LARC) is the most effective
      reversible method to prevent unplanned pregnancies. Variability in state-level
      policies and the high cost of LARC could create substantial inconsistencies in
      Medicaid coverage, despite federal guidance aimed at enhancing broad access. This
      study surveyed state Medicaid payment policies and outreach activities related to
      LARC to explore the scope of services covered. METHODS: Using publicly available
      information, we performed a content analysis of state Medicaid family planning
      and LARC payment policies. Purposeful sampling led to a selection of nine states
      with diverse geographic locations, political climates, Medicaid expansion status,
      and the number of women covered by Medicaid. RESULTS: All nine states' Medicaid
      programs covered some aspects of LARC. However, only a single state's payment
      structure incorporated all core aspects of high-quality LARC service delivery,
      including counseling, device, insertion, removal, and follow-up care. Most states
      did not explicitly address counseling, device removal, or follow-up care. Some
      states had strategies to enhance access, including policies to increase device
      reimbursement, stocking and delivery programs to remove cost barriers, and
      covering devices and insertion after an abortion. CONCLUSIONS: Although Medicaid
      policy encourages LARC methods, state payment policies frequently fail to address
      key aspects of care, including counseling, follow-up care, and removal, resulting
      in highly variable state-level practices. Although some states include payment
      policy innovations to support LARC access, significant opportunities remain.

PMID- 29329990
TI  - Transcatheter Aortic Valve Implantation in Morphologically Complex Root
      Aneurysms.
AB  - Performing transcatheter aortic valve implantation in the presence of
      aneurysmatic aortopathy is widely contraindicated but needs to be taken into
      account as a bailout strategy in selected patients. Deliberate preoperative
      assessment of measurements becomes the crucial key element in this context. After
      meticulous valve selection, retrograde access is obtained through the right
      subclavian artery additionally serving as a backup arterial cannulation site in
      case of conversion. Transcatheter aortic valve implantation is then performed
      through the transapical route. Transcatheter aortic valve implantation in complex
      aneurysmatic aortic morphology is feasible in highly selected patients after
      comprehensive preoperative evaluation. The present article describes our initial
      experience, safeguards, and technical details.

PMID- 29329991
TI  - Dynamic contrast-enhanced EUS for quantification of tumor perfusion in colonic
      cancer: a prospective cohort study.
AB  - BACKGROUND AND AIMS: Dynamic contrast-enhanced EUS (CE-EUS) for quantification of
      perfusion in colonic tumors has not previously been reported in the literature.
      The aim of this study was to investigate correlations between perfusion
      parameters and vessel density assessed by immunohistochemical staining with
      antibodies toward CD31 and CD105. METHODS: We conducted a prospective clinical
      study of 28 patients with left-sided colonic adenocarcinoma who underwent CE-EUS
      and left-sided hemicolectomy within 2 weeks. CE-EUS recordings were analyzed in 2
      regions of interest: the entire tumor and the most enhanced area.
      Immunohistochemical staining with CD31 and CD105 was performed on tumor tissue
      sections. The slides were manually scanned for highly vascularized areas, and
      counting of vessels was performed in hotspots within the tumor and invasive
      front. New vasculature was assessed by CD105. Associations between CE-EUS and
      CD31 and CD105 were investigated using Spearman correlation. RESULTS: We found
      significant P values for the correlation between CD31 and rise time (rho = .603
      [95% confidence interval (95% CI), .238-.816]; P = .001) in tumor tissue and for
      the correlation between CD31 and rise time (rho = .50 [95% CI, .201-.695]; P =
      .008) and fall time (rho = .52 [95% CI, .204-.723]; P = .006) corresponding to
      the invasive front. We found no correlations between perfusion values evaluated
      by CE-EUS and CD105. CONCLUSIONS: Our results show a significant correlation for
      vessel density evaluated by CD31 and perfusion parameters evaluated by CE-EUS.
      This may be the first step toward using real-time CE-EUS for monitoring
      antiangiogenic therapies in colonic cancer. (Clinical trial registration number:
      NCT02324023.).

PMID- 29329993
TI  - Pulmonary arterial hypertension in four patients treated by leflunomide.
AB  - Pulmonary arterial hypertension (PAH) is a rare disorder that can be drug
      induced, mostly following treatment by appetite-suppressant drugs. We report four
      cases of patients who developed PAH following a treatment by leflunomide for
      rheumatoid arthritis, psoriatic arthritis or undetermined connective tissue
      disease. All patients described a progressive dyspnea from grade II to IV of NYHA
      classification; clinical examination found signs of heart failure. PAH was
      finally diagnosed and confirmed by right heart catheterisation. Haemodynamic
      explorations found pre-capillary pulmonary hypertension with mean pulmonary
      arterial pressure above 25mmHg, and pulmonary capillary wedge pressure under
      15mmHg. Explorations of this pre-capillary pulmonary hypertension were conducted
      according to international guidelines: pulmonary or chronic thromboembolic
      aetiologies were excluded after ventilation/perfusion lung scan and high
      resolution computed tomography. All other etiologic explorations were negative.
      Imputability of leflunomide was finally retained. Leflunomide was stopped for all
      patients; three of them received specific PAH treatments. A favourable clinical
      and/or haemodynamic evolution was observed for all patients. The conclusions of
      the investigations conducted by our pharmacovigilance centre were communicated to
      the European Medicines Agency, leading to the addition of "pulmonary
      hypertension" in the paragraph "special warning and precautions of use" of the
      package leaflet of leflunomide.

PMID- 29329992
TI  - EUS elastography (strain ratio) and fractal-based quantitative analysis for the
      diagnosis of solid pancreatic lesions.
AB  - BACKGROUND AND AIMS: EUS elastography is useful in characterizing solid
      pancreatic lesions (SPLs), and fractal analysis-based technology has been used to
      evaluate geometric complexity in oncology. The aim of this study was to evaluate
      EUS elastography (strain ratio) and fractal analysis for the characterization of
      SPLs. METHODS: Consecutive patients with SPLs were prospectively enrolled between
      December 2015 and February 2017. Elastographic evaluation included parenchymal
      strain ratio (pSR) and wall strain ratio (wSR) and was performed with a new
      compact US processor. Elastographic images were analyzed using a computer program
      to determine the 3-dimensional histogram fractal dimension. A composite
      cytology/histology/clinical reference standard was used to assess sensitivity,
      specificity, positive predictive value, negative predictive value, and area under
      the receiver operating curve. RESULTS: Overall, 102 SPLs from 100 patients were
      studied. At final diagnosis, 69 (68%) were malignant and 33 benign. At
      elastography, both pSR and wSR appeared to be significantly higher in malignant
      as compared with benign SPLs (pSR, 24.5 vs 6.4 [P < .001]; wSR, 56.6 vs 15.3 [P <
      .001]). When the best cut-off levels of pSR and wSR at 9.10 and 16.2,
      respectively, were used, sensitivity, specificity, positive predictive value,
      negative predictive value, and area under the receiver operating curve were
      88.4%, 78.8%, 89.7%, 76.9%, and 86.7% and 91.3%, 69.7%, 86.5%, 80%, and 85.7%,
      respectively. Fractal analysis showed a significant statistical difference (P =
      .0087) between the mean surface fractal dimension of malignant lesions (D = 2.66
      +/- .01) versus neuroendocrine tumor (D = 2.73 +/- .03) and a statistical
      difference for all 3 channels red, green, and blue (P < .0001). CONCLUSIONS: EUS
      elastography with pSR and fractal-based analysis are useful in characterizing
      SPLs. (Clinical trial registration number: NCT02855151.).

PMID- 29329994
TI  - Authors' response to the comments to "Structured pharmacist-led intervention
      programme to improve medication adherence in COPD patients: A randomized
      controlled study".

PMID- 29329995
TI  - Multifunctional hybrid graphene oxide for circulating tumor cell isolation and
      analysis.
AB  - Even in 21st century, >90% cancer-associated deaths are caused by metastatic
      disease. Circulating tumor cells (CTCs), which circulate in the blood stream
      after release from primary tumors, extravasate and form fatal metastases in
      different organs. Several clinical trials indicate that CTCs can be used as a
      liquid biopsy of tumors for early diagnosis of cancers. Since CTCs are extremely
      rare and exhibit heterogeneous biology due to epithelial-mesenchymal transition
      (EMT), oncologists continue to face enormous challenges in using CTCs as a true
      "liquid biopsy" for cancer patients. Recent advancements in nanoscience allow us
      to design nano-architectures with the capability of targeted CTCs isolation and
      identification. In the current review, we discuss contribution from different
      groups on the development of graphene oxide based nanoarchitecture for effective
      isolation and accurate identification of CTCs from whole blood. In the last few
      years, using zero-dimensional (0D), two dimensional (2D) and three dimensional
      (3D) multifunctional hybrid graphene oxide (GO), different types of
      nanoarchitectures have been designed. These nanoarchitectures represent a highly
      powerful platform for CTC diagnosis. We discuss the major design criteria that
      have been used to develop hybrid GO nanoarchitectures for selective capture and
      accurate identification of heterogeneous CTCs from whole blood. At the end, we
      conclude with the promises, major challenges, and prospect to clinically
      translate the identification of CTCs using GO based nanotechnology.

PMID- 29329996
TI  - To prep or not to prep - that is the question: A randomized trial on the use of
      antiflatulent medication as part of bowel preparation for patients having image
      guided external beam radiation therapy to the prostate.
AB  - INTRODUCTION: Radiation therapy is a standard treatment option for prostate
      cancer. With growing use of escalated doses and tighter margins, procedures to
      limit rectal size variation are needed to reduce prostate motion, increase
      treatment accuracy, and minimize rectal toxicity. This prospective study was done
      to determine whether the introduction of an antiflatulent medication would
      decrease rectal distention at computed tomography (CT) simulation and throughout
      a course of radiation therapy. METHODS AND MATERIALS: Patients undergoing a
      radical course of radiation therapy to the prostate/prostate bed were eligible to
      participate. Participants were randomly assigned to the intervention arm
      (antiflatulent medication) or the control arm (no medication). For each
      participant, the number of CT simulation rescans was recorded. Rectal diameters
      were measured on CT simulation and treatment cone beam CT scans. Acute rectal
      toxicities were assessed at baseline and weekly using National Cancer Institute
      Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.0. A chi2
      analysis was used to compare the number of participants requiring a rescan in
      each study arm. Change in rectal diameter over time was assessed using repeated
      measures analysis of variance. RESULTS: A total of 78 patients participated, with
      equal numbers assigned to each study arm. There was no significant difference
      between arms in the number of participants requiring a CT simulation rescan (P =
      .5551). There was no significant variation in rectal diameter between arms (P =
      .8999); however, there was a significant effect of time (P = .0017) and a
      significant interaction effect between study arm and time on rectal diameter (P =
      .0141). No acute rectal toxicities above grade 2 were reported. CONCLUSIONS: The
      addition of antiflatulent medication did not affect the frequency of CT
      simulation rescans. Both time and the interaction between study arm and time had
      a statistically significant effect on rectal diameter, although neither finding
      was clinically significant. Instead, standardized bowel preparation education
      developed for this study may have been sufficient to limit rectal size variation.

PMID- 29329997
TI  - Clinical log data analysis for assessing the accuracy of the CyberKnife fiducial
      free lung tumor tracking system.
AB  - PURPOSE: The CyberKnife Xsight Lung Tracking (XLT) and 1-View tracking systems
      can synchronize beam targeting to a visible lung tumor with respiratory motion
      during irradiation without requiring internal fiducial markers. The systems use a
      correlation model that relates external marker positions to tumor positions as
      well as a prediction model that predicts the target's future position. In this
      study, the correlation and prediction model uncertainties related to the
      CyberKnife fiducial-free tumor tracking system were evaluated using clinical log
      data. METHODS AND MATERIALS: Data from 211 fractions in 42 patients with lung
      tumors were analyzed. Log files produced by the CyberKnife Synchrony system were
      acquired after each treatment; the mean correlation and prediction errors for
      each patient were calculated. Additionally, we examined the tracking tumor
      related parameters and analyzed the relationships between the model errors and
      tracking tumor-related parameters. RESULTS: The overall means +/- standard
      deviations (SDs) of the correlation errors were 0.70 +/- 0.43 mm, 0.36 +/- 0.16
      mm, 0.44 +/- 0.22 mm, and 0.95 +/- 0.43 mm for the superoinferior (SI), left
      right (LR), anteroposterior (AP), and radial directions, respectively. The
      overall means +/- SDs of the prediction errors were 0.13 +/- 0.11 mm, 0.03 +/-
      0.02 mm, 0.03 +/- 0.02 mm, and 0.14 +/- 0.11 mm for the SI, LR, AP, and radial
      directions, respectively. There were no significant differences in these errors
      between the XLT and 1-View tracking methods. The tumor motion amplitude was
      moderately associated with the correlation error and strongly related to the
      prediction error in the SI and radial directions. CONCLUSIONS: Clinical log data
      analysis can be used to determine the necessary margin sizes in treatment plans
      to compensate for correlation and prediction errors in the CyberKnife fiducial
      free lung tumor tracking system. The tumor motion amplitude may facilitate margin
      determination.

PMID- 29329998
TI  - Common error pathways seen in the RO-ILS data that demonstrate opportunities for
      improving treatment safety.
AB  - PURPOSE: The Radiation Oncology Incident Learning System (RO-ILS) receives event
      reports from facilities across the country. This effort extracted common error
      pathways seen in the data. These pathways, expressed as fault trees, demonstrate
      the need for, and opportunities for, preventing these errors and/or limiting
      their propagation to treatment. METHODS AND MATERIALS: As of the third quarter of
      2016, 2344 event reports had been submitted to RO-ILS and reviewed. A total of
      396 of the reports judged highest priority were rereviewed and assigned up to 3
      keywords to classify events. Based on patterns among the keyword assignments, the
      data were further aggregated into pathways leading to 3 general error types:
      "problematic plan approved for treatment," "wrong shift instructions given to
      therapists," and "wrong shift performed at treatment." Fault trees were created
      showing how different errors at different stages in the treatment process combine
      to flow into these general error types. RESULTS: A total of 173 of the 396 (44%)
      events were characterized as belonging to 1 of these 3 general error types.
      Ninety-nine events were defined as "problematic plan approved for treatment," 40
      as "wrong shift instructions given to therapists," and 34 as "wrong shift
      performed at treatment." Seventy-six of these events (44%) resulted in
      incorrectly delivered treatment. Event discovery was by therapists (n = 76),
      physicists (n = 45), physicians (n = 23), dosimetrists (n = 15), or not
      identified (n = 9); 5 events were found as a result of the patient questioning
      the staff. For the event type "problematic plan approved for treatment," 64 of
      the 99 (65%) events were attributable to physician error: incorrect target or
      dosing pattern prescribed. CONCLUSIONS: Data extracted from RO-ILS event reports
      demonstrate common error pathways in radiation oncology that propagate all the
      way to treatment. Additional study and coordination of efforts is needed to
      develop and share best practices to address the sources of these errors and
      curtail their propagation.

PMID- 29329999
TI  - Understanding melanocortin-4 receptor control of neuronal circuits: Toward novel
      therapeutics for obesity syndrome.
AB  - It is well known that melanocortin-4 receptors (MC4Rs) and central melanocortin
      pathways regulate food intake, energy expenditure, and glucose homeostasis.
      Importantly, MC4R deficiency is the most common monogenic cause of human obesity.
      Interestingly, MC4Rs expressed by distinct central nuclei are responsible for the
      different physiological function of MC4R stimulation. In addition, MC4Rs activate
      multiple intracellular and/or synaptic signaling molecules for the regulation of
      neuronal circuits. Therefore, MC4Rs and the downstream signal molecules are
      plausible targets for development of novel therapeutics against obesity and
      obesity-related metabolic disorders. In this review, we discuss recent findings
      on the neuronal circuits and signaling molecules that are responsible for MC4R
      control energy balance and autonomic function. Further, we review status of MC4R
      agonists as novel therapeutics for obesity syndrome. We believe that
      comprehensive understanding of signaling molecules involved in MC4R control of
      neuronal circuits will help to design MC4R agonists as safe and effective anti
      obesity drugs.

PMID- 29330000
TI  - Histotripsy Treatment of Benign Prostatic Enlargement Using the Vortx Rx System:
      Initial Human Safety and Efficacy Outcomes.
AB  - OBJECTIVE: To assess clinical safety (primary) and efficacy (secondary) of
      histotripsy for treatment of symptomatic benign prostatic enlargement in a first
      in human study. METHODS: Twenty-five male subjects with moderate to severe lower
      urinary tract symptoms, prostate size between 30 and 80 g, and no evidence of
      prostate cancer were enrolled at 2 sites in a prospective, single-arm study.
      Treatment consisted of acoustic energy delivery through the perineum with
      integrated real-time transrectal ultrasound monitoring using the Vortx Rx system.
      Follow-up evaluations were performed on postoperative day 1 and 1, 3, and 6
      months. RESULTS: Twenty-five men underwent histotripsy treatment with no serious
      intraoperative adverse events. Postoperatively, 3 cases of transient urinary
      retention (<3 days), 1 case of urinary retention (8 days in duration, defined as
      serious), a minor anal abrasion, and microscopic hematuria were considered device
      related adverse events. Debulking of targeted prostate tissue was not observed
      with transrectal ultrasound imaging or with endoscopic visualization, and
      clinically meaningful improvement in uroflow or postvoid residual urine (PVR) did
      not occur. However, International Prostate Symptom Score improvement at 1 month
      was 12.5 (52.4%) +/- 6.6 points (n = 25), at 3 months was 11.9 (50.8%) +/- 7.6
      points (n = 24), and at 6 months was 10.4 (44.0%) +/- 7.6 points (n = 24) (P
      <.001). CONCLUSION: Prostate histotripsy was safe and well tolerated in this
      pilot human trial with improvement in lower urinary tract symptoms.

PMID- 29330001
TI  - In-bore 3.0-T Magnetic Resonance Imaging-guided Transrectal Targeted Prostate
      Biopsy in a Repeat Biopsy Population: Diagnostic Performance, Complications, and
      Learning Curve.
AB  - OBJECTIVE: To evaluate the diagnostic performance and complication rate of the in
      bore magnetic resonance imaging-guided transrectal targeted prostate biopsy
      (MRGB) in a repeat biopsy population on the basis of a nearly 4-year learning
      curve (2014-2017). MATERIALS AND METHODS: A total of 142 consecutive males with
      previous biopsies and persistent suspicion of prostate cancer (PCa) due to high
      prostate-specific antigen level initially underwent MRGB in the case of prostate
      imaging reporting and data system (PI-RADS) 3-5 lesions. Cancer detection rate
      (CDR), number and length of cores, biopsy time, operator experience,
      complications, and prediction of clinically significant (cs) PCa (Gleason score
      >=7) were investigated. RESULTS: PCa was found in 57% of patients. CDR in PI-RADS
      3, 4, and 5 lesions were 46%, 52%, and 74%, respectively. csPCa was found in 9%,
      25%, and 48% of patients. In univariate analysis the PI-RADS score (P = .0067)
      was a significant predictor of csPCa. In the multivariate logistic regression,
      age (P = .0007), number of previous biopsies (P = .0236), and prostate-specific
      antigen density (P = .0250) were significant predictors of csPCa. Location and
      size of the index lesion, number and length of cores obtained, and operator
      experience did not affect CDR. Concerning learning curve, biopsy time and number
      of cores obtained improved significantly after 10 procedures. Complications
      requiring medical intervention were seen in 6% (infections 2%). CONCLUSION: In a
      re-biopsy setting the MRGB showed sufficient diagnostic performance in detecting
      csPCa in PI-RADS 3-5 lesions, with low complication rate. The skill of performing
      biopsy is quickly acquired, and location of index lesion did not have an impact
      on CDR.

PMID- 29330002
TI  - Choosing a healthy and sustainable diet: A three-level approach for understanding
      the drivers of the Italians' dietary regime over time.
AB  - Dietary patterns play key roles in health promotion and in preserving the
      environment. A growing number of studies show the importance of individual
      factors on food consumption choices, such as socio-economic status, lifestyle
      variables and contextual and social factors that characterize the geographical
      area in which individuals reside. The Mediterranean Diet is a sustainable diet
      that respects the environment, thus reducing per capita emissions from food
      production in respect to less sustainable diet. The aim of this paper is to
      determine the Italians' prevailing food patterns using a composite indicator and
      to identify which factors determine a higher adherence to the Mediterranean Diet
      in Italy. By using 15 waves of the ISTAT "Aspect of Daily Life" survey, we
      constructed an original data set and referred to the multilevel approach which
      enabled us to distinguish between temporal and cross-sectional effects thus
      providing valuable insights to policy makers and stakeholders in order to promote
      the Mediterranean Diet and reap environmental and public health. The results show
      that education plays an important role in determining food consumption behavior
      while the tendency to practice sports on a regular basis and to have breakfast
      and lunch at home positively influence people's adherence to this diet.

PMID- 29330003
TI  - Effects of 5-HT5A receptor blockade on amnesia or forgetting.
AB  - Previously the effects (0.01-3.0 mg/kg) of post-training SB-699551 (a 5-HT5A
      receptor antagonist) were reported in the associative learning task of
      autoshaping, showing that SB-699551 (0.1 mg/kg) decreased lever-press conditioned
      responses (CR) during short-term (STM; 1.5-h) or (3.0 mg/kg) long-term memory
      (LTM; 24-h); relative to the vehicle animals. Moreover, as pro-cognitive efficacy
      of SB-699551 was reported in the ketamine-model of schizophrenia. Hence, firstly
      aiming improving performance (conditioned response, CR), in this work autoshaping
      lever-press vs. nose-poke response was compared; secondly, new set of animals
      were randomly assigned to SB-699551 plus forgetting or amnesia protocols. Results
      show that the nose-poke operandum reduced inter-individual variance, increased CR
      and produced a progressive CR until 48-h. After one week of no training/testing
      sessions (i.e., interruption of 216 h), the forgetting was observed; i.e., the
      CR% of control-saline group significantly decreased. In contrast, SB-699551 at
      0.3 and 3.0 mg/kg prevents forgetting. Additionally, as previously reported the
      non-competitive NMDA receptor antagonist dizocilpine (0.2 mg/kg) or the non
      selective cholinergic antagonist scopolamine (0.3 mg/kg) decreased CR in STM. SB
      699551 (0.3 mg/kg) alone also produced amnesia-like effect. Co-administration of
      SB-699551-dizocilpine or SB-699551-scopolamine reversed the SB-699551 induced
      amnesic effects in LTM (24-h). Nose-poke seems to be a reliable operandum. The
      anti-amnesic and anti-forgetting mechanisms of amnesic SB-699551-dose remain
      unclear. The present findings are consistent with the notion that low doses of 5
      HT5A receptor antagonists might be useful for reversing memory deficits
      associated to forgetting and amnesia. Of course, further experiments are
      necessary.

PMID- 29330005
TI  - A Phase I Study of Irinotecan, Capecitabine (Xeloda), and Oxaliplatin in Patients
      With Advanced Colorectal Cancer.
AB  - BACKGROUND: The objective of the present phase I study was to define the dose
      limiting toxicities (DLTs) and maximum tolerated dose (MTD) of irinotecan,
      capecitabine, and oxaliplatin given in combination (IXO regimen) to patients with
      previously untreated, unresectable advanced or metastatic colorectal cancer
      (CRC). PATIENTS AND METHODS: Patients received oxaliplatin followed by irinotecan
      as intravenous infusions on day 1, with oral capecitabine taken twice daily (BID)
      on days 2 to 15 of a 3-week cycle. The dose ranges were explored as follows:
      oxaliplatin, 75 to 120 mg/m2; irinotecan, 160 to 230 mg/m2; capecitabine, 750 to
      1000 mg/m2 BID. Dose escalation was performed individually for each drug at each
      dose level according to the type and severity of toxicity encountered in the
      previous cohort. RESULTS: A total of 39 patients were enrolled at 7 dose levels
      and the MTD. The recommended doses for phase II evaluation were oxaliplatin 100
      mg/m2, irinotecan 160 mg/m2, and capecitabine 950 mg/m2 BID. Diarrhea and febrile
      neutropenia were DLTs. Of the 39 enrolled patients, 26 (67%) had confirmed
      objective responses. The median progression-free survival was 11 months, and the
      median overall survival was 25 months. The survival rate at 5 years was 23%.
      CONCLUSION: The IXO regimen has a manageable toxicity profile with promising
      antitumor activity as first-line treatment of advanced and metastatic CRC.

PMID- 29330004
TI  - Recovery of stress-impaired social behavior by an antagonist of the CRF binding
      protein, CRF6-33, in the bed nucleus of the stria terminalis of male rats.
AB  - Social stress is recognized to promote the development of neuropsychiatric and
      mood disorders. Corticotropin releasing factor (CRF) is an important neuropeptide
      activated by social stress, and it contributes to neural and behavioral
      adaptations, as indicated by impaired social interactions and anhedonic effects.
      Few studies have focused on the role of the CRF binding protein (CRFBP), a
      component of the CRF system, and its activity in the bed nucleus of stria
      terminalis (BNST), a limbic structure connecting amygdala and hypothalamus. In
      this study, animals' preference for sweet solutions was examined as an index of
      stress-induced anhedonic responses in Wistar rats subjected to four brief
      intermittent episodes of social defeat. Next, social approach was assessed after
      local infusions of the CRFBP antagonist, CRF fragment 6-33 (CRF6-33) into the
      BNST. The experience of brief episodes of social defeat impaired social approach
      behaviors in male rats. However, intra-BNST CRF6-33 infusions restored social
      approach in stressed animals to the levels of non-stressed rats. CRF6-33 acted
      selectively on social interaction and did not alter general exploration in nether
      stressed nor non-stressed rats. These findings suggest that BNST CRFBP is
      involved in the modulation of anxiety-like responses induced by social stress.

PMID- 29330006
TI  - Cue and context conditioning to respiratory threat: Effects of suffocation fear
      and implications for the etiology of panic disorder.
AB  - Interoceptive threats play a crucial role in the etiology of panic disorder (PD).
      While body sensations may become conditioned stimuli (CS) when paired with such
      interoceptive threats (cue conditioning), the environment in which such
      interoceptive threats occur may also be learned as a predictor of threat (context
      conditioning). Suffocation fear (SF) might facilitate these associative learning
      processes if threats of suffocation become relevant as unconditioned stimuli
      (US). To investigate whether SF affects associative learning during such
      respiratory threat, we used mild dyspnea as CS that predicted the occurrence of
      strong dyspnea (US) in one context (predictable), was not related to the
      occurrence of the US in another context (unpredictable) or was presented in a
      different context (safe) in which no US was delivered. Startle eyeblink responses
      and subjective reports were assessed in 34 participants during learning.
      Individuals reporting high SF showed a clear potentiation of the startle response
      during the interoceptive CS predicting the occurrence of interoceptive threat
      (US). Such startle potentiation was not observed when the CS remained unpaired
      (safe or unpredictable context). Moreover, high SF persons also showed a
      significant startle potentiation to the threatening context, when the CS did not
      predict the onset of the US. No such learning effects were observed for low SF
      individuals. The data support the view that defensive response mobilization can
      be triggered by cues but also by contexts that predict the occurrence of
      interoceptive threats if these threats are relevant for the individuals,
      supporting learning accounts for the development of PD.

PMID- 29330008
TI  - Electrophysiological brain indices of risk behavior modification induced by
      contingent feedback.
AB  - The main aim of this research was to study the effects of response feedback on
      risk behavior and the neural and cognitive mechanisms involved, as a function of
      the feedback contingency. Sixty drivers were randomly assigned to one of three
      feedback groups: contingent, non-contingent and no feedback. The participants'
      task consisted of braking or not when confronted with a set of risky driving
      situations, while their electroencephalographic activity was continuously
      recorded. We observed that contingent feedback, as opposed to non-contingent
      feedback, promoted changes in the response bias towards safer decisions. This
      behavioral modification implied a higher demand on cognitive control, reflected
      in a larger amplitude of the N400 component. Moreover, the contingent feedback,
      being predictable and entailing more informative value, gave rise to smaller SPN
      and larger FRN scores when compared with non-contingent feedback. Taken together,
      these findings provide a new and complex insight into the neurophysiological
      basis of the influence of feedback contingency on the processing of decision
      making under risk. We suggest that response feedback, when contingent upon the
      risky behavior, appears to improve the functionality of the brain mechanisms
      involved in decision-making and can be a powerful tool for reducing the tendency
      to choose risky options in risk-prone individuals.

PMID- 29330009
TI  - The ALMANACH Project: Preliminary results and potentiality from Afghanistan.
AB  - INTRODUCTION: ALMANACH (ALgorithms for the MANagement of Acute CHildhood
      illnesses) is an electronic version of IMCI (Integrated Management of Childhood
      Illness) running on tablets. ALMANACH enhances its concept, it integrates well
      into health staff's daily consultation work and facilitates diagnosis and
      treatment. ALMANACH informs when to refer a child or to perform a rapid
      diagnostic test (RDT), recommends the right treatment dosage and synchronizes
      collected data real time with a Health Management Information System (DHIS2) for
      epidemiological evaluation and decision making. OBJECTIVES: Since May 2016,
      ALMANACH is under investigational deployment in three primary health care
      facilities in Afghanistan with the goal to improve the quality of care provided
      to children between 2 months and 5 years old. METHODS: IMCI's algorithms were
      updated in considering latest scientific publications, national guidelines,
      innovations in RDTs, the target population's epidemiological profile and the
      local resources available. Before the implementation of the project, a direct
      observation of 599 consultations was carried out to assess the daily performance
      at three selected health facilities in Kabul. RESULTS: The baseline survey showed
      that nutritional screening, vitamin A supplementation and deworming were not
      systematically performed: few patients were diagnosed for malnutrition (1.8%),
      received vitamin A (2.7%) or deworming (7.5%). Physical examination was
      appropriate only for 23.8% of the diagnoses of respiratory or gastrointestinal
      diseases, ear infection and sore throat. Respiratory rate was checked only in
      33.5% of the children with fever and cough, dehydration status was assessed in
      only 16.5% of the diarrhoea cases. Forty-seven percent of patients received
      incorrect treatment. Sixty-four percent of the children, before the introduction
      of ALMANACH, received at least one antibiotic, although for 87.1% antibiotic
      therapy was unnecessary. The review of 8'047 paediatric consultations between May
      2016 and September 2017 showed that with ALMANACH, malnutrition detection,
      deworming and Vitamin A supplementation increased respectively to 4.4%, 50.2% and
      27.5%. Antibiotic prescription decreased to 21.83% and all children were examined
      and treated in compliance with the protocols. CONCLUSION: A survey will be
      conducted one year after the implementation to validate these initial promising
      results. If the efficacy of the approach is confirmed, ALMANACH could establish
      as a powerful innovation for primary health care.

PMID- 29330007
TI  - Lost connections: Oxytocin and the neural, physiological, and behavioral
      consequences of disrupted relationships.
AB  - In humans and rodent animal models, the brain oxytocin system is paramount for
      facilitating social bonds, from the formation and consequences of early-life
      parent-infant bonds to adult pair bond relationships. In social species, oxytocin
      also mediates the positive effects of healthy social bonds on the partners' well
      being. However, new evidence suggests that the negative consequences of early
      neglect or partner loss may be mediated by disruptions in the oxytocin system as
      well. With a focus on oxytocin and its receptor, we review studies from humans
      and animal models, i.e. mainly from the biparental, socially monogamous prairie
      vole (Microtus ochrogaster), on the beneficial effects of positive social
      relationships both between offspring and parents and in adult partners. The
      abundance of social bonds and benevolent social relationships, in general, are
      associated with protective effects against psycho- and physiopathology not only
      in the developing infant, but also during adulthood. Furthermore, we discuss the
      negative effects on well-being, emotionality and behavior, when these bonds are
      diminished in quality or are disrupted, for example through parental neglect of
      the young or the loss of the partner in adulthood. Strikingly, in prairie voles,
      oxytocinergic signaling plays an important developmental role in the ability to
      form bonds later in life in the face of early-life neglect, while disruption of
      oxytocin signaling following partner loss results in the emergence of depressive
      like behavior and physiology. This review demonstrates the translational value of
      animal models for investigating the oxytocinergic mechanisms that underlie the
      detrimental effects of developmental parental neglect and pair bond disruption,
      encouraging future translationally relevant studies on this topic that is so
      central to our daily lives.

PMID- 29330010
TI  - Nasopharyngeal Lactobacillus is associated with a reduced risk of childhood
      wheezing illnesses following acute respiratory syncytial virus infection in
      infancy.
AB  - BACKGROUND: Early life acute respiratory infection (ARI) with respiratory
      syncytial virus (RSV) has been strongly associated with the development of
      childhood wheezing illnesses, but the pathways underlying this association are
      poorly understood. OBJECTIVE: To examine the role of the nasopharyngeal
      microbiome in the development of childhood wheezing illnesses following RSV ARI
      in infancy. METHODS: We conducted a nested cohort study of 118 previously
      healthy, term infants with confirmed RSV ARI by RT-PCR. We used next-generation
      sequencing of the V4 region of the 16S ribosomal RNA gene to characterize the
      nasopharyngeal microbiome during RSV ARI. Our main outcome of interest was 2-year
      subsequent wheeze. RESULTS: Of the 118 infants, 113 (95.8%) had 2-year outcome
      data. Of these, 46 (40.7%) had parental report of subsequent wheeze. There was no
      association between the overall taxonomic composition, diversity, and richness of
      the nasopharyngeal microbiome during RSV ARI with the development of subsequent
      wheeze. However, the nasopharyngeal detection and abundance of Lactobacillus was
      consistently higher in infants who did not develop this outcome. Lactobacillus
      also ranked first among the different genera in a model distinguishing infants
      with and without subsequent wheeze. CONCLUSIONS: The nasopharyngeal detection and
      increased abundance of Lactobacillus during RSV ARI in infancy are associated
      with a reduced risk of childhood wheezing illnesses at age 2 years.

PMID- 29330012
TI  - Basophil testing with CD63 in pollen-sensitized patients is independent of the
      circadian clock.

PMID- 29330011
TI  - Mutations in PI3K110delta cause impaired natural killer cell function partially
      rescued by rapamycin treatment.
AB  - BACKGROUND: Heterozygous gain-of-function mutations in PI3K110delta lead to
      lymphadenopathy, lymphoid hyperplasia, EBV and cytomegalovirus viremia, and
      sinopulmonary infections. OBJECTIVE: The known role of natural killer (NK) cell
      function in the control of EBV and cytomegalovirus prompted us to investigate the
      functional and phenotypic effects of PI3K110delta mutations on NK cell subsets
      and cytotoxic function. METHODS: Mutations in patients were identified by using
      whole-exome or targeted sequencing. We performed NK cell phenotyping and
      functional analysis of patients' cells using flow cytometry, standard Cr51
      cytotoxicity assays, and quantitative confocal microscopy. RESULTS: PI3K110delta
      mutations led to an altered NK cell developmental phenotype and cytotoxic
      dysfunction. Impaired NK cell cytotoxicity was due to decreased conjugate
      formation with susceptible target cells and abrogated activation of cell
      machinery required for target cell killing. These defects were restored partially
      after initiation of treatment with rapamycin in 3 patients. CONCLUSION: We
      describe novel NK cell functional deficiency caused by PI3K110delta mutation,
      which is a likely contributor to the severe viremia observed in these patients.
      Rapamycin treatment partially restores NK cell function, providing a further
      rationale for its use in patients with this disease.

PMID- 29330014
TI  - Frequency of red blood cell genotypes in multi-transfused patients and blood
      donors from Minas Gerais, Southeast Brazil.
AB  - BACKGROUND AND OBJECTIVES: The frequency of red blood cell (RBC) antigens in
      Brazil varies due to differences in the ethnic groups in different regions;
      however, these studies have not been performed in Minas Gerais, where African
      admixture is more prevalent in comparison with other states. Due to these facts,
      this study aimed to determine the frequency of RBC genotypes on Rh, Kell, Duffy
      and Kidd systems in blood donors and multi-transfused patients from Minas Gerais,
      Southeast Brazil. METHODS: Blood samples were collected from 170 donors and 117
      patients with different diagnosis and at least three RBC transfusions. DNA was
      extracted from leukocytes and genotyped by PCR-SSP, Multiplex or RFLP to alleles
      of the referred systems. The results were compared by the Chi-Square test, with a
      significance level of 5%. RESULTS: The most frequent genotypes were: RHD+,
      RHCE*ce/RHCE*ce, KEL*2/KEL*2, FY*B-67T/FY*B-67T and JK*A/JK*B. FY*B-67C/FY*B-67C,
      RHD*Psi and JK*A/JK*A genotypes were more prevalent in sickle cell disease (SCD)
      patients than in donors. Many differences in RBC genotype frequencies were
      observed in comparison with studies from other states and countries. CONCLUSION:
      The results reinforce the importance of determining RBC genotypes of blood donors
      and patients in different regions of Brazil and the world, improving the
      transfusion safety of individuals requiring chronic RBC transfusions, especially
      those with SCD, due to ethnic differences in relation to donors.

PMID- 29330013
TI  - A functional splice variant associated with decreased asthma risk abolishes the
      ability of gasdermin B to induce epithelial cell pyroptosis.
AB  - BACKGROUND: Genetic variants in the chromosomal region 17q21 are consistently
      associated with asthma. However, mechanistic studies have not yet linked any of
      the associated variants to a function that could influence asthma, and as a
      result, the identity of the asthma gene(s) remains elusive. OBJECTIVES: We sought
      to identify and characterize functional variants in the 17q21 locus. METHODS: We
      used the Exome Aggregation Consortium browser to identify coding (amino acid
      changing) variants in the 17q21 locus. We obtained asthma association measures
      for these variants in both the Genetic Epidemiology Research in Adult Health and
      Aging (GERA) cohort (16,274 cases and 38,269 matched controls) and the EVE
      Consortium study (5,303 asthma cases and 12,560 individuals). Gene expression and
      protein localization were determined by quantitative RT-PCR and fluorescence
      immunostaining, respectively. Molecular and cellular studies were performed to
      determine the functional effects of coding variants. RESULTS: Two coding variants
      (rs2305480 and rs11078928) of the gasdermin B (GSDMB) gene in the 17q21 locus
      were associated with lower asthma risk in both GERA (odds ratio, 0.92; P = 1.01 *
      10-6) and EVE (odds ratio, 0.85; joint PEVE = 1.31 * 10-13). In GERA, rs11078928
      had a minor allele frequency (MAF) of 0.45 in unaffected (nonasthmatic) controls
      and 0.43 in asthma cases. For European Americans in EVE, the MAF of rs2305480 was
      0.45 for controls and 0.39 for cases; for all EVE subjects, the MAF was 0.32 for
      controls and 0.27 for cases. GSDMB is highly expressed in differentiated airway
      epithelial cells, including the ciliated cells. We found that, when the GSDMB
      protein is cleaved by inflammatory caspase-1 to release its N-terminal fragment,
      potent pyroptotic cell death is induced. The splice variant rs11078928 deletes
      the entire exon 6, which encodes 13 amino acids in the critical N-terminus, and
      abolishes the pyroptotic activity of the GSDMB protein. CONCLUSIONS: Our study
      identified a functional asthma variant in the GSDMB gene of the 17q21 locus and
      implicates GSDMB-mediated epithelial cell pyroptosis in pathogenesis.

PMID- 29330015
TI  - Mother-to-child transmission of extended-spectrum-beta-lactamase-producing
      Enterobacteriaceae.
AB  - BACKGROUND: Preterm infants are at high risk for extended-spectrum-beta-lactamase
      producing Enterobacteriaceae (ESBL-E) sepsis and neonatal intensive care unit
      (NICU) outbreaks. Maternal colonization with ESBL-E may be precursory to mother
      to-child transmission. However, there is no consensus regarding surveillance of
      pregnant women for ESBL-E colonization. AIM: To identify pairs of mothers and
      infants harbouring same-strain ESBL-E colonization and to determine whether
      maternal transmission may play a role in increasing ESBL-E carriage in preterm
      infants. METHODS: This was a one-year analysis from an ongoing, prospective ESBL
      E surveillance of mothers of premature infants and their offspring. Mother-infant
      pairs colonized with the same bacteria underwent strain analysis using pulsed
      field gel electrophoresis (PFGE). Clinical parameters were collected from the
      hospital computerized records. FINDINGS: Between January 2015 and January 2016,
      313/409 (76.5%) mothers and all 478 (100%) infants were screened for ESBL-E
      colonization; carriage rates were 21.5% and 14.8%, respectively. Four (5.6%)
      colonized infants developed late-onset sepsis and two (2.8%) died. Twenty-five
      mother-infant pairs colonized with the same bacterial strain were identified; a
      subgroup of 10 pairs of isolates underwent PFGE, and 70% displayed an identical
      PFGE fingerprint. No similarities were found between isolates recovered from
      unrelated neonates and mothers. ESBL-E colonization was found significantly
      earlier in infants of mothers colonized at birth (P<0.001) compared with infants
      of non-colonized mothers. CONCLUSIONS: ESBL-E carriage rates in mothers and NICU
      infants with non-negligible maternal-neonatal ESBL-E transmission in the study
      region indicate that maternal colonization surveillance and/or further infection
      control interventions should be considered.

PMID- 29330016
TI  - Clinical impact of delayed catheter removal for patients with central-venous
      catheter-related Gram-negative bacteraemia.
AB  - BACKGROUND: Gram-negative bacteria are increasingly the cause of catheter-related
      bloodstream infection (CRBSI), and the prevalence of multi-drug-resistant strains
      is rising rapidly. This study evaluated the impact of delayed central venous
      catheter (CVC) removal on clinical outcomes in patients with Gram-negative CRBSI.
      METHODS: Between January 2007 and December 2016, patients with Gram-negative
      bacteraemia and CVC placement, from two tertiary care hospitals, were included
      retrospectively. Cases with CVC removal more than three days after onset of
      bacteraemia or without CVC removal were classified as having delayed CVC removal.
      RESULTS: In total, 112 patients were included. Of these, 78 had CRBSI (43
      definite and 35 probable) and 34 had Gram-negative bacteraemia from another
      source (non-CRBSI). Enterobacteriaceae were less common pathogens in patients
      with CRBSI than in patients with non-CRBSI (11.5% vs 41.3%; P<0.001). Delayed CVC
      removal was associated with increased 30-day mortality (40.5% vs 11.8%; P=0.01)
      in patients with Gram-negative CRBSI; this was not seen in patients with non
      CRBSI (25.0% vs 14.3%; P>0.99). Delayed CVC removal [odds ratio (OR) 6.8], multi
      drug-resistant (MDR) Gram-negative bacteraemia (OR 6.3) and chronic renal failure
      (OR 11.1) were associated with 30-day mortality in patients with CRBSI. The
      protective effect of early CVC removal on mortality was evident in the MDR group
      (48.3% vs 18.2%; P=0.03), but not in the non-MDR group (11.1% vs 0%; P=0.43).
      CONCLUSION: CVCs should be removed early to improve clinical outcomes in patients
      with Gram-negative CRBSI, especially in settings where MDR isolates are
      prevalent.

PMID- 29330017
TI  - A wrapped multi-label classifier for the automatic diagnosis and prognosis of
      Alzheimer's disease.
AB  - BACKGROUND: AD is the most frequent neurodegenerative disease, severely impacting
      our society. Early diagnosis and prognosis are challenging tasks in the
      management of AD patients. NEW METHOD: We implemented a machine-learning
      classifier for the automatic early diagnosis and prognosis of AD by means of
      features extracted, selected and optimized from structural MRI brain images. The
      classifier was designed to perform multi-label automatic classification into the
      following four classes: HC, ncMCI, cMCI, and AD. RESULTS: From our analyses, it
      emerged that MMSE and hippocampus-related measures must be included as primary
      measures in automatic-classification systems for both the early diagnosis and the
      prognosis of AD. The voting scheme mainly based on the binary-classification
      performances on the different four groups is the best choice to model the multi
      label decision function for AD, when compared with a simple majority-vote scheme
      or with a scheme aimed at discriminating patients with high vs low risk of
      conversion to AD and therapy addressing. COMPARISON WITH EXISTING METHOD(S): The
      accuracies of our binary classifications were higher than or comparable to
      previously published methods. An improvement is needed on the approach we used to
      combine binary-classification outputs to obtain the final multi-label
      classification. CONCLUSIONS: The performance of multi-label automatic
      classification systems strongly depends on the choice of the voting scheme used
      for combining binary-classification labels.

PMID- 29330018
TI  - Testicular adrenal rest tumor screening and fertility counseling among males with
      congenital adrenal hyperplasia.
AB  - BACKGROUND: Reduced fertility is a common potential problem among males with
      congenital adrenal hyperplasia (CAH), with nearly half experiencing impaired
      sperm production. The major cause of oligo/azoospermia in CAH is testicular
      adrenal rest tumors (TARTs). Studies indicate that ultrasound screening for TARTs
      should begin during childhood, yet it remains unclear whether boys with CAH are
      routinely screened for TARTs and/or counseled about infertility risk and
      potential interventions such as fertility testing and/or preservation. OBJECTIVE:
      The purpose of this study was to examine TART screening and fertility counseling
      practices among boys with CAH. STUDY DESIGN: An IRB-approved retrospective chart
      review was conducted of all males with ICD-9/10 codes for CAH (2007-2016) at a
      large pediatric academic center to examine: age and indication for diagnosis; age
      at first and last documented pediatric endocrinology and urology visit; history
      of ultrasound examinations; and documentation of fertility counseling. RESULTS:
      Forty-six patients were included, of whom 38 had 21-hydroxylase deficiency.
      Median age at diagnosis was 2 weeks (range 7 days-10 years). Median age at the
      most recent pediatric endocrinology clinic visit was 14 years (range 2-42 years).
      Twenty-nine patients were >11 years old (63% of the sample) at the time of the
      study and 14 of these were >18 years old (30% of the sample). Seven patients
      (15%) had a screening ultrasound at some point in their care, of whom three had
      TARTs. Fertility was mentioned in the records of six subjects (13% of the
      sample). Six of the subjects (13%) had any mention of fertility in their records.
      None of the patients had biochemical testing or semen analysis to assess gonadal
      function, and none were offered fertility preservation. Only one patient was seen
      by a pediatric urologist. DISCUSSION: Despite the limitations of a single-center
      retrospective design, our findings highlight that TART screening and fertility
      counseling remain underutilized in boys with CAH. There is a need for increased
      awareness and development of practice guidelines within pediatric urology and
      endocrinology to address this common and understudied problem. CONCLUSION: In
      addition to a screening ultrasound in puberty and consideration of semen analysis
      after puberty, these boys may benefit from seeing a pediatric urologist
      independently or in an interdisciplinary program. Boys with CAH and their
      families should be educated about infertility risk and potential interventions,
      with the goal of improving reproductive outcomes in this population.

PMID- 29330019
TI  - Parental decisional regret and views about optimal timing of female genital
      restoration surgery in congenital adrenal hyperplasia.
AB  - PURPOSE: The role of female genital restoration surgery (FGRS) in girls with
      congenital adrenal hyperplasia (CAH) is controversial, with no long-term parent
      reported outcomes available. Decisional regret (DR) affects most parents after
      their children's treatment of pediatric conditions, including hypospadias. We
      aimed to assess parental DR after FGRS in infancy or toddlerhood and explore
      optimal timing for surgery. MATERIALS AND METHODS: One-hundred and six parents of
      females with CAH undergoing FGRS before 3 years old and followed at our
      institution (1999-2017) were invited to enroll online. Higher Decision Regret
      Scale (DRS) scores indicated greater DR (range 0-100). Participants also reported
      preferred FGRS timing relative to their surgery (earlier, same, later/delayed).
      Non-parametric statistical tests were used. RESULTS: Thirty-nine parents (median
      4.4 years after FGRS) participated (36.8% response rate). Median age at FGRS was
      9 months. Median DRS score was 0 (mean: 5.0). Overall, 20.5% of parents reported
      some regret (all mild-moderate) (Figure). Fewer parents reported DR after FGRS
      compared with published DR after hypospadias repair (50-92%, p <= 0.001) or
      adenotonsillectomy (41-45%, p <= 0.03). No parent preferred delayed FGRS. Seven
      parents (18.1%) preferred earlier surgery, especially when performed after
      birthday (80.0% vs. 8.8%, p = 0.004). DISCUSSION: We present the first report of
      validated long-term parent-reported outcomes after FGRS in infant and toddler
      girls with CAH. One limitation is that this is largely a single surgeon series.
      Reasons for the observed low levels of DR are likely multifactorial. Far from a
      definitive study, we aimed to provide parents willing to share about their
      experience an opportunity to do so. For that reason, selection bias may exist in
      our study. While parents with higher DR were potentially less likely to
      participate because of mistrust of the medical establishment, those with a
      negative experience may in fact be more likely to voice their opinions. A low
      participation rate was likely a result of the sensitive nature of FGRS, a desire
      for privacy, and inability to locate parents. A larger study will be required to
      assess how DR is affected by sexual function, genital appearance and
      complications, and DR among women with CAH. CONCLUSIONS: Parents of females with
      CAH report low levels of DR after FGRS in infancy and toddlerhood. This appears
      to be lower than after other genital and non-genital pediatric procedures. When
      present, parental DR is usually mild. No parents preferred delayed surgery, even
      among those with DR. Some preferred earlier surgery.

PMID- 29330020
TI  - Predictors of deep brain stimulation outcome in tremor patients.
AB  - BACKGROUND: Deep brain stimulation of the ventro-intermedius nucleus of the
      thalamus is an established treatment for tremor of differing etiologies but
      factors that may predict the short- and especially long-term outcome of surgery
      are still largely unknown. METHODS: We retrospectively investigated the clinical,
      pharmacological, electrophysiological and anatomical features that might predict
      the initial response and preservation of benefit in all patients who underwent
      deep brain stimulation for tremor. Data were collected at the following time
      points: baseline (preoperative), one-year post-surgery, and most recent visit.
      Tremor severity was recorded using the Fahn-Tolosa-Marin Tremor Rating Scale
      and/or the Unified Parkinson's Disease Rating Scale. RESULTS: A total of 52
      patients were included in the final analysis: 31 with essential tremor, 15 with
      cerebellar tremor of different etiologies, and 6 with Parkinson's disease. Long
      term success (mean follow-up duration 34.7 months, range 1.7-121.1 months) was
      reported in 63.5%. Predictors of long-term benefit were: underlying tremor
      etiology (best outcome in Parkinson's disease, worst outcome in cerebellar
      tremor); age at surgery (the older the better); baseline tremor severity (the
      greater the better); lack of response to benzodiazepines; a more anterior
      electrode placement and single-unit beta power (the greater the better).
      CONCLUSIONS: Specific patients' features (including single unit beta activity)
      and electrode locations may predict the short- and long-term benefit of thalamic
      stimulation for tremor. Future prospective studies enrolling a much larger sample
      of patients are needed to substantiate the associations detected by this
      retrospective study.

PMID- 29330022
TI  - Extracellular matrix contribution to skin wound re-epithelialization.
AB  - The ability of skin to act as a barrier is primarily determined by cells that
      maintain the continuity and integrity of skin and restore it after injury.
      Cutaneous wound healing in adult mammals is a complex multi-step process that
      involves overlapping stages of blood clot formation, inflammation, re
      epithelialization, granulation tissue formation, neovascularization, and
      remodeling. Under favorable conditions, epidermal regeneration begins within
      hours after injury and takes several days until the epithelial surface is intact
      due to reorganization of the basement membrane. Regeneration relies on numerous
      signaling cues and on multiple cellular processes that take place both within the
      epidermis and in other participating tissues. A variety of modulators are
      involved, including growth factors, cytokines, matrix metalloproteinases,
      cellular receptors, and extracellular matrix components. Here we focus on the
      involvement of the extracellular matrix proteins that impact epidermal
      regeneration during wound healing.

PMID- 29330021
TI  - CCN4/WISP1 controls cutaneous wound healing by modulating proliferation,
      migration and ECM expression in dermal fibroblasts via alpha5beta1 and TNFalpha.
AB  - Understanding the mechanisms that control cutaneous wound healing is crucial to
      successfully manage repair of damaged skin. The goal of the current study was to
      uncover novel extracellular matrix (ECM) components that control the wound
      healing process. Full thickness skin defects were created in mice and used to
      show CCN4 up-regulation during wound-healing as early as 1 day after surgery,
      suggesting a role in inflammation and subsequent dermal migration and
      proliferation. To determine how CCN4 could regulate wound healing we used Ccn4-KO
      mice and showed they had delayed wound closure accompanied by reduced expression
      of Col1a1 and Fn mRNA. Boyden chamber assays using Ccn4-deficient dermal
      fibroblasts showed they have reduced migration and proliferation compared to WT
      counterparts. To confirm CCN4 has a role in proliferation and migration of dermal
      cells, siRNA knockdown and transduction of CCN4 adenoviral transduction were used
      and resulted in reduced or enhanced migration of human adult dermal fibroblast
      (hADF) cells respectively. The induced migration of the dermal fibroblasts by
      CCN4 appears to work via alpha5beta1 integrin receptors that further stimulates
      down-stream ERK/JNK signaling. The regulation of CCN4 by TNF-alpha prompted us
      look further at their potential relationship. Treatment of hADFs with CCN4 and
      TNF-alpha alone or together showed CCN4 counteracted the inhibition of TNF-alpha
      on COL1A1 and FN mRNA expression and the stimulation of TNF-alpha on MMP-1 and
      MMP3 mRNA expression. CCN4 appeared to counterbalance the effects of TNF-alpha by
      inhibiting downstream NF-kappaB/p-65 signaling. Taken together we show CCN4
      stimulates dermal fibroblast cell migration, proliferation and inhibits TNF-alpha
      stimulation, all of which could regulate wound healing.

PMID- 29330023
TI  - Unraveling the differential structural stability and dynamics features of T7
      endolysin partially folded conformations.
AB  - BACKGROUND: Characterization of partially collapsed protein conformations at
      atomic level is a daunting task due to their inherent flexibility and
      conformational heterogeneity. T7 bacteriophage endolysin (T7L) is a single-domain
      amidase that facilitates the lysis of Gram-negative bacteria. T7L exhibits a pH
      dependent structural transition from native state to partially folded (PF)
      conformation. In the pH range 5-3, T7L PF states display differential ANS binding
      characteristics. METHODS: CD, fluorescence, NMR spectroscopy and lysis assays
      were used to investigate the structure-stability- dynamics relationships of T7L
      PF conformations. RESULTS: Structural studies indicated a partial loss of
      secondary/tertiary structures compared to its native state. The loss in the
      tertiary structure and the hydrophobic core opening increases upon decrease of pH
      from 5 to 3. Thermal denaturation experiments delineated that the pH 5
      conformation is thermally irreversible in contrast to pH 3, depicting that
      hydrophobic core opening is essential for thermal reversibility. Further, urea
      dependent unfolding features of PF state at pH 5 and 4 evidenced for a collapsed
      conformation at intermediate urea concentrations. Residue level studies revealed
      that alpha1-helix and beta3-beta4 segment of T7L are the major contributors for
      such a structural collapse and inherent dynamics. CONCLUSIONS: The results
      suggested that the low pH PF states of T7L are heterogeneous and exhibits
      differential structural, unfolding, thermal reversibility, and dynamic features.
      GENERAL SIGNIFICANCE: Unraveling the structure-stability characteristics of
      different endolysin conformations is essential for designing novel chimeric and
      engineered phage endolysins as broadband antimicrobial agents over a varied pH
      range.

PMID- 29330025
TI  - The role of extracellular and intracellular Nicotinamide phosphoribosyl
      transferase in cancer: Diagnostic and therapeutic perspectives and challenges.
AB  - Nicotinamide phosphoribosyl-transferase (Nampt) or pre-B cell colony-enhancing
      factor or visfatin represents a pleiotropic molecule acting as an enzyme, a
      cytokine and a growth factor. Intracellular Nampt plays an important role in
      cellular bioenergetics and metabolism, particularly NAD biosynthesis. NAD
      biosynthesis is critical in DNA repair, oncogenic signal transduction,
      transcription, genomic integrity and apoptosis. Although its insulin-mimetic
      function remains a controversial issue, extracellular Nampt presents
      proliferative, anti-apoptotic, pro-inflammatory, pro-angiogenic and metastatic
      properties. Nampt is upregulated in many malignancies, including obesity
      associated cancers, and is associated with worse prognosis. Serum Nampt may be a
      potential diagnostic and prognostic biomarker in cancer. Pharmacologic agents
      that neutralize Nampt or medications that decrease Nampt levels or downregulate
      signaling pathways downstream of Nampt may prove to be useful anti-cancer
      treatments. In particular, Nampt inhibitors as monotherapy or in combination
      therapy have displayed anti-cancer activity in vivo and in vitro. The aim of this
      review is to explore the role of Nampt in cancer pathophysiology as well as to
      synopsize the mechanisms underlying the association between extracellular and
      intracellular Nampt, and malignancy. Exploring the interplay of cellular
      bioenergetics, inflammation and adiposopathy is expected to be of importance in
      the development of preventive and therapeutic strategies against cancer.

PMID- 29330024
TI  - Nucleophosmin-1 regions associated with acute myeloid leukemia interact
      differently with lipid membranes.

PMID- 29330026
TI  - Sound shock response in larval zebrafish: A convenient and high-throughput
      assessment of auditory function.
AB  - Given that hearing ability can be challenged in diverse ways, it is necessary to
      develop an easily conducted, high-throughput method for assessing potential
      auditory risks. Measuring the acoustic startle response (ASR) has become a
      critical behavioral method in hearing research using zebrafish (Danio rerio). In
      this study, changes in the activity of zebrafish larvae (10 days post
      fertilization (dpf)) due to exposure to a sudden easily-generated broad-band
      noise were automatically and objectively recorded and analyzed without building
      sophisticated equipments. A significant increase in activity was induced by the
      noise stimulation and the alterations were impaired by gentamicin. In addition, a
      clear dose-response trend was observed between gentamicin exposure and the
      impaired activity, and a similar phenomenon was observed between gentamicin
      exposure and damage to hair cells. Our results suggested that alterations in the
      activity induced by a broad-band noise can potentially be used as an efficient
      assay for assessing hearing ability.

PMID- 29330027
TI  - Selective estrogen receptor modulator ormeloxifene suppresses embryo implantation
      via inducing miR-140 and targeting insulin-like growth factor 1 receptor in rat
      uterus.
AB  - Ormeloxifene, the non-steroidal SERM contraceptive, inhibits endometrial
      receptivity and embryo implantation via countering nidatory estrogen. However,
      the molecular mechanism of ormeloxifene action responsible for its contraceptive
      efficacy still remains unclear. Herein, we aimed to identify the miRNAs modulated
      under the influence of ormeloxifene and to explore their role in endometrial
      receptivity and embryo implantation. By doing microRNA sequencing analysis, a
      total of 168 miRNAs were found to be differentially expressed in uterine tissue
      of ormeloxifene-treated rats, on day 5 (10:00 h) of pregnancy i.e. peri
      implantation period. Out of differentially expressed miRNAs, miR-140 expression
      was found to be elevated in ormeloxifene administered groups and was selected for
      detailed investigation. In-vivo gain-of-function of miR-140 resulted in a
      significant reduction of implantation sites indicating its role in embryo
      implantation. The experiment on delayed implantation showed that estradiol caused
      down-regulation of miR-140. It also suppressed the attachment and outgrowth of
      BeWo spheroids to RL95-2 endometrial cells. In transwell migration assay, miR-140
      was found to be involved in suppression of migration and invasion of endometrial
      epithelial cells. The ormeloxifene treatment caused up-regulation of miR-140
      along with down-regulated expression of its target IGF1R in endometrial
      epithelial and stromal cells which also led to the suppression of downstream
      effectors integrin beta3 and FAK. In mimic miR-140 receiving horn, the reduced
      expression of IGF1R was observed along with suppressed downstream integrin beta3
      and FAK similar to that observed in uteri of ormeloxifene- treated rats. Taken
      together, these findings suggest that ormeloxifene-induced inhibition of embryo
      implantation occurs via inducing miR-140 and altering its target IGF1R in rat
      uterus.

PMID- 29330028
TI  - Perceptions of the relative harmfulness of marijuana and alcohol among adults in
      Oregon.
AB  - This study documents perceptions of the relative harmfulness of marijuana and
      alcohol to a person's health among adults in Oregon just before the first legal
      sales of marijuana for recreational use. We surveyed 1941 adults in Oregon in
      September 2015. Respondents were recruited using an address-based sampling (ABS)
      frame (n = 1314) and social media advertising (n = 627). Respondents completed
      paper surveys (ABS-mail, n = 388) or online surveys (ABS-online, n = 926; social
      media, n = 627). We used descriptive statistics and logistic regression models to
      examine perceptions of the relative harmfulness of marijuana and alcohol by
      sample characteristics, including substance use. About half of adults in Oregon
      (52.5%) considered alcohol to be more harmful to a person's health than
      marijuana. A substantial proportion considered the substances equally harmful
      (40.0%). Few considered marijuana to be more harmful than alcohol (7.5%). In
      general, respondents who were younger, male, and not Republican were more likely
      than others to consider alcohol more harmful than marijuana. Respondents who were
      older, female, and Republican were more likely to consider marijuana and alcohol
      equally harmful. Most individuals who reported using both marijuana and alcohol
      (67.7%) and approximately half of those who used neither substance (48.2%)
      considered alcohol to be more harmful than marijuana. Perceptions about the
      relative harmfulness of marijuana and alcohol may have implications for public
      health. As state lawmakers develop policies to regulate marijuana, it may be
      helpful to consider the ways in which those policies may also affect use of
      alcohol and co-use of alcohol and marijuana.

PMID- 29330029
TI  - Association of 100% fruit juice consumption and 3-year weight change among
      postmenopausal women in the in the Women's Health Initiative.
AB  - The association between drinking 100% fruit juice and long-term weight gain is
      controversial and has been investigated in few studies. We examined whether 100%
      fruit juice consumption was associated with weight change in a large prospective
      cohort of postmenopausal women. We analyzed data from 49,106 postmenopausal women
      in the United States enrolled in the Women's Health Initiative between 1993 and
      1998. Food frequency questionnaires at baseline and year 3 assessed food and
      beverage intake. Body weight was measured at in-person clinic visits. We used
      linear mixed effects modeling to determine the association between change in 100%
      fruit juice consumption and 3-year weight change over the same time period.
      Covariates of interest included age, demographic factors, smoking, body mass
      index, hormone replacement therapy, lifestyle factors, change in whole fruit
      intake, and change in sugar-sweetened beverage intake. The mean weight change was
      3.2 lbs. over 3 years. In multivariable adjusted analyses, each 1 serving/day
      increase in 100% fruit juice intake was associated with a 3-year weight gain of
      0.39 lbs. (95% confidence interval: 0.10, 0.69). In conclusion, an increase in
      100% fruit juice consumption was associated with a small amount of long-term
      weight gain in postmenopausal women.

PMID- 29330030
TI  - Health impact assessment of cycling network expansions in European cities.
AB  - We conducted a health impact assessment (HIA) of cycling network expansions in
      seven European cities. We modeled the association between cycling network length
      and cycling mode share and estimated health impacts of the expansion of cycling
      networks. First, we performed a non-linear least square regression to assess the
      relationship between cycling network length and cycling mode share for 167
      European cities. Second, we conducted a quantitative HIA for the seven cities of
      different scenarios (S) assessing how an expansion of the cycling network [i.e.
      10% (S1); 50% (S2); 100% (S3), and all-streets (S4)] would lead to an increase in
      cycling mode share and estimated mortality impacts thereof. We quantified
      mortality impacts for changes in physical activity, air pollution and traffic
      incidents. Third, we conducted a cost-benefit analysis. The cycling network
      length was associated with a cycling mode share of up to 24.7% in European
      cities. The all-streets scenario (S4) produced greatest benefits through
      increases in cycling for London with 1,210 premature deaths (95% CI: 447-1,972)
      avoidable annually, followed by Rome (433; 95% CI: 170-695), Barcelona (248; 95%
      CI: 86-410), Vienna (146; 95% CI: 40-252), Zurich (58; 95% CI: 16-100) and
      Antwerp (7; 95% CI: 3-11). The largest cost-benefit ratios were found for the 10%
      increase in cycling networks (S1). If all 167 European cities achieved a cycling
      mode share of 24.7% over 10,000 premature deaths could be avoided annually. In
      European cities, expansions of cycling networks were associated with increases in
      cycling and estimated to provide health and economic benefits.

PMID- 29330031
TI  - Mental health disorders mediate association of sexual minority identity with
      cardiovascular disease.
AB  - BACKGROUND: Little is known about cardiovascular health disparities for lesbian,
      gay, or bisexual (LGB) persons and whether these disparities are mediated by
      mental health disorders due to sexual minority stress. We hypothesize LGB
      identity is associated with an increased risk of cardiovascular disease (CVD) and
      that major depressive disorder (MDD) and generalized anxiety disorders (GAD) may
      mediate this association. METHODS: The National Epidemiologic Survey on Alcohol
      and Related Conditions is a longitudinal, nationally-representative study of non
      institutionalized U.S. adults. We cross-sectionally analyzed the second wave data
      (2004-2005) comparing 577 self-identified LGB persons to 33,598 heterosexuals.
      Multiple logistic regression modeling and mediation analysis (the product of
      coefficients approach) were performed. RESULTS: LGB persons had significantly
      higher CVD prevalence [adjusted odds ratio (AOR): 1.5, 95% CI: 1.2-1.9], and were
      more likely to be diagnosed with MDD (AOR: 1.9, 1.8-2.1), GAD (AOR: 2.2, 1.9
      2.4), or co-occurring MDD and GAD (AOR: 2.2, 2.0-2.5). MDD, GAD, and co
      occurrence of MDD and GAD significantly mediated 14.3%, 22.2%, and 33.3% of the
      association of LGB status with increased CVD prevalence, respectively.
      CONCLUSIONS: Our findings identified a 50% increased CVD prevalence among LGB
      persons and this increased risk was mediated in part by MDD and GAD, both being
      more prevalent in sexual minority adults.

PMID- 29330032
TI  - A free sugars daily value (DV) identifies more "less healthy" prepackaged foods
      and beverages than a total sugars DV.
AB  - Regulatory changes in Canada will require food labels to have a benchmark [%
      Daily Value, %DV] for total sugars, based on 100 g/day, while US labels will
      require a %DV for added sugars, based on 50 g/day. The objective of this study
      was to compare two labelling policies, a total sugars DV (100 g/day) and a free
      sugars DV (50 g/day) on food labels. This cross-sectional analysis of the Food
      Label Information Program database focussed on top sources of total sugars intake
      in Canada (n = 6924 foods). Products were categorized as "less healthy" using two
      sets of criteria: a) free sugars levels exceeding the WHO guidelines (>=10%
      energy from free sugars); and b) exceeding healthfulness cut-offs of the Food
      Standards Australia New Zealand Nutrient Profiling Scoring Criterion (FSANZ
      NPSC). The proportion of "less healthy" products with >=15%DV (defined as "a lot"
      of sugars i.e. high in sugars, based on Health Canada's %DV labelling footnote
      and educational message for dietary guidance) were compared for each sugar
      labelling scenario. The free sugars DV showed better alignment with both methods
      for assessing "healthfulness" than the total sugars DV. The free sugars DV
      identified a greater proportion of "less healthy" foods with >=15%DV, based on
      both the FSANZ-NPSC (70% vs. 45%, p < .0001) and WHO guidelines (82% vs. 55%, p <
      .0001); particularly in sweet baked goods, sugars and preserves, chocolate bars,
      confectionery, and frozen desserts categories. Compared to total sugars DV
      labelling, using a free sugars DV identified more "less healthy" foods. Findings
      support the adoption of free sugars labelling.

PMID- 29330033
TI  - Service quality and parents' willingness to get adolescents HPV vaccine from
      pharmacists.
AB  - We sought to examine whether pharmacy service quality was associated with
      parents' willingness to have immunizing pharmacists administer human
      papillomavirus (HPV) vaccine to their adolescent children. Participants were a
      national sample of 1504 US parents of adolescents ages 11 to 17 who completed an
      online survey in 2014. Analyses used structural equation modeling. Parents rated
      service quality and feelings of satisfaction with their pharmacies as moderate to
      high. Many (44%) were willing to get HPV vaccine from immunizing pharmacists for
      their adolescent children. Compared with parents who went to chain pharmacies,
      parents who went to independent pharmacies gave higher ratings of service quality
      (professionalism, confidentiality, milieu, all p < .001). Parents who went to
      clinic pharmacies, compared with parents who went to chain pharmacies gave lower
      ratings for milieu (p < .01). Parents who went to independent pharmacies had
      lower willingness to get HPV vaccine from pharmacists compared to parents who
      went to chain pharmacies (p = .001), but there was no difference in willingness
      for parents who went to clinic versus chain pharmacies. Service quality and
      satisfaction partially mediated the effect between independent pharmacies
      compared to chain pharmacies and willingness (p < .05). Parents who knew their
      pharmacists or expressed more confidence in HPV vaccine also had higher
      willingness to get their children HPV vaccine from pharmacist. Many parents were
      willing to go to immunizing pharmacists for their children's HPV vaccination.
      Pharmacies that are considering offering HPV vaccine may be able to improve
      vaccine uptake by increasing perception of service quality.

PMID- 29330034
TI  - Successful treatment of a penicillin-intermediate and ceftriaxone-resistant
      Granulicatella adiacens presumed prosthetic valve endocarditis with vancomycin.
AB  - Advancements in rapid diagnostics have helped to identify nutritionally variant
      streptococci (NVS) as an increasing cause of infective endocarditis (IE). This
      case report highlights the challenges in susceptibility testing and the
      importance of appropriate empiric treatment for Granulicatella adiacens, and
      provides considerations for future practice guideline recommendations. Guidelines
      for treatment of IE caused by NVS are currently limited to patients with native
      valve disease. We present a patient with presumed prosthetic valve endocarditis
      caused by G. adiacens, with clinically relevant resistance to recommended first
      line agents (penicillin and ceftriaxone), who was successfully treated with 8
      weeks of intravenous (IV) vancomycin. Vancomycin is currently recommended as an
      alternate therapy for patients intolerant of penicillins, but we believe
      vancomycin should be considered a first-line empiric treatment option for IE when
      the identified organism is G. adiacens and susceptibility testing is not readily
      available.

PMID- 29330036
TI  - Regulation of fibrotic changes by the synergistic effects of cytokines,
      dimensionality and matrix: Towards the development of an in vitro human dermal
      hypertrophic scar model.
AB  - : Current therapeutic strategies to reduce scarring in full thickness skin defect
      offer limited success due to poor understanding of scar tissue formation and the
      underlying signaling pathways. There is an urgent need to develop human cell
      based in vitro scar tissue models as animal testing is associated with ethical
      and logistic complications and inter-species variations. Pro-inflammatory
      cytokines play critical role in regulating scar development through complex
      interplay and interaction with the ECM and corresponding signaling pathways. In
      this context, we assessed the responses of cultured fibroblasts with respect to
      their differentiation into myofibroblasts using optimised cytokines (TGF-beta1,
      IL-6 and IL-8) for scar formation in 2D (tissue culture plate, collagen type I
      coated plate) vs 3D collagen type I gel based constructs. We attempted to deduce
      the role of dimensionality of cell culture matrix in modulating differentiation,
      function and phenotype of cultured fibroblasts. Validation of the developed model
      showed similarity to etiology and pathophysiology of in vivo hypertrophic scar
      with respect to several features: 1) transition of fibroblasts to myofibroblasts
      with convincing expression of alpha-SMA stress fibers; 2) contraction; 3)
      excessive collagen and fibronectin secretion; 4) expression of fibrotic ECM
      proteins (SPARC and Tenascin); 5) low MMP secretion. Most importantly, we
      elucidated the involvement of TGF-beta/SMAD and Wnt/beta-catenin pathways in
      developing in vitro dermal scar. Hence, this relatively simple in vitro human
      scar tissue equivalent may serve as an alternative for testing and designing of
      novel therapeutics and help in extending our understanding of the complex
      interplay of cytokines and related dermal scar specific signaling. STATEMENT OF
      SIGNIFICANCE: Scarring of the skin affects almost millions of people per year in
      the developed world alone, nevertheless the complex pathophysiology and the
      precise signaling mechanisms responsible for this phenomenon of skin scarring are
      still unknown. A number of anti-scar drugs are being developed and being tested
      on animals and monolayer models. However, testing the efficacy of these drugs on
      lab based 3D in vitro models may prove extremely useful in recapitulating the 3D
      microenvironment of the native scar tissue. In that context in this study we have
      demonstrated the development of 3D in vitro dermal scar model, by optimizing a
      constellation of factors, such as combination of cytokines (TGF-beta1,IL-6,IL-8)
      and cellular dimensionality in inducing the differentiation of dermal fibroblasts
      to myofibroblasts. This in vitro scar model was successful in replicating
      hallmark features of hypertrophic scar such as excessive synthesis of fibrotic
      extracellular matrix, perturbed matrix homeostasis, contraction, diminished MMP
      synthesis. The study also highlighted significant involvement of TGF-beta/SMAD
      and Wnt/beta-catenin signaling pathways in in vitro scar formation.

PMID- 29330035
TI  - Harmine enhances GABAergic transmission onto basoamygdala projection neurons in
      mice.
AB  - Emerging evidence indicates that loss of inhibitory tone in amygdala with its
      subsequent overactivation contributes to the development of multiple mental
      disorders such as anxiety disorders and post-traumatic stress disorder (PTSD).
      Harmine is a member of natural beta-carboline alkaloids which can readily cross
      the blood brain barrier and displays significant antidepressant and anxiolytic
      effects in rodents. However, the underlying neurobiological mechanisms are
      largely unknown. Here, by using whole-cell patch clamp recordings in in vitro
      amygdala slices, we examined the effect of harmine on glutamatergic and GABAergic
      transmission onto basal amygdala (BA) projection neurons (PNs). Our results
      showed that harmine affected neither the amplitude nor the frequency of
      spontaneous and miniature excitatory postsynaptic currents (sEPSCs/mEPSCs) of
      PNs. By contrast, it markedly increased both the amplitude and frequency of the
      spontaneous inhibitory postsynaptic currents (sIPSCs). For mIPSCs, only an
      increase of their frequency but not amplitude was observed following harmine
      perfusion, suggesting that harmine might act through presynaptic mechanism. In
      parallel, a reduction of paired-pulse ratio of evoked IPSCs emerged in the
      presence of harmine. Furthermore, the intrinsic excitability of PNs was
      dramatically decreased upon harmine treatment. Together, our study suggests that
      harmine selectively potentiates the inhibitory but not excitatory transmission
      onto BA PNs, which may contribute to its antidepressant and anxiolytic influence.

PMID- 29330037
TI  - Sustained delivery of glial cell-derived neurotrophic factors in collagen
      conduits for facial nerve regeneration.
AB  - : Facial nerve injury caused by traffic accidents or operations may reduce the
      quality of life in patients, and recovery following the injury presents unique
      clinical challenges. Glial cell-derived neurotrophic factor (GDNF) is important
      in nerve regeneration; however, soluble GDNF rapidly diffuses into body fluids,
      making it difficult to achieve therapeutic efficacy. In this work, we developed a
      rat tail derived collagen conduit to connect nerve defects in a simple and safe
      manner. GDNF was immobilized in the collagen conduits via chemical conjugation to
      enable controlled release of GDNF. The GDNF delivery system prevented rapid
      diffusion from the site without impacting bioactivity of GDNF; degradation of the
      collagen conduit was inhibited owing to the chemical conjugation. The artificial
      nerve conduit was then used to examine facial nerve regeneration across a facial
      nerve defect. Following transplantation, the artificial nerve conduits degraded
      gradually without causing dislocations and serious inflammation, with good
      integration into the host tissue. Functional and histological tests indicated
      that the artificial nerve conduits were able to guide the axons to grow through
      the defect, reaching the distal stumps. The degree of nerve regeneration in the
      group that was treated with the artificial nerve conduit approached that of the
      autograft group, and exceeded that of the other conduit grafted groups. STATEMENT
      OF SIGNIFICANCE: In this study, we developed artificial nerve conduits consisting
      of GDNF immobilized on collagen, with the aim of providing an environment for
      nerve regeneration. Our results show that the artificial nerve conduits guided
      the regeneration of axons to the distal nerve segment. GDNF was immobilized
      stably in the artificial nerve conduits, and therefore retained a sufficient
      concentration at the target site to effectively promote the regeneration process.
      The artificial nerve conduits exhibited good biocompatibility and facilitated
      nerve regeneration and functional recovery with an efficacy that was close to
      that of an autograft, and better than that of the other conduit grafted groups.
      Our approach provides an effective delivery system that overcomes the rapid
      diffusion of GDNF in body fluids, promoting peripheral nerve regeneration. The
      artificial nerve conduit therefore qualifies as a putative candidate material for
      the fabrication of peripheral nerve reconstruction devices.

PMID- 29330038
TI  - Asthmatic/wheezing phenotypes in preschool children: Influential factors, health
      care and urban-rural differences.
AB  - BACKGROUND: Different wheezing and asthmatic phenotypes turned out to indicate
      differences in etiology, risk factors and health care. We examined influential
      factors and urban-rural differences for different phenotypes. METHODS: Parents of
      4732 children filled out a questionnaire concerning children's health and
      environmental factors administered within the Health Monitoring Units (GME) in a
      cross-sectional study in Bavaria, Germany (2014/2015). To classify respiratory
      symptoms, five phenotype groups were built: episodic, unremitting and frequent
      wheeze, ISAAC (International Study of Asthma and Allergies in Children) - asthma
      and physician-diagnosed asthma (neither of the groups are mutually exclusive).
      For each phenotype, health care variables were presented and stratified for
      residence. Urban-rural differences were tested by Pearson's chi-squared tests.
      Multivariable logistic regression was performed to analyze associations between
      influential factors and belonging to a phenotype group, and to compare groups
      with regard to health care variables as outcome. RESULTS: Risk factors for
      wheezing phenotypes were male gender (OR = 2.02, 95%-CI = [1.65-2.48]), having
      older siblings (OR = 1.24, 95%-CI = [1.02-1.51]), and preterm delivery (OR =
      1.61, 95%-CI = [1.13-2.29]) (ORs for unremitting wheeze). 57% of children with
      ISAAC asthma and 74% with physician-diagnosed asthma had performed allergy tests.
      Medication intake among all groups was more frequent in rural areas, and
      physician's asthma diagnoses were more frequent in urban areas. CONCLUSIONS: In
      accordance with previous research this study confirms that male gender, older
      siblings and preterm delivery are associated with several wheezing phenotypes.
      Overall, low numbers of allergy tests among children with physician's diagnoses
      highlight a discrepancy between common practice and current knowledge and
      guidelines. Residential differences in health care might encourage further
      research and interventions strategies.

PMID- 29330039
TI  - Age as a prognostic indicator for adjuvant therapy in patients who underwent
      pancreatic resections for cancer.
AB  - PURPOSE: In pancreatic cancer, the greatest increase in survival is attained by
      surgical resection followed by adjuvant chemotherapy. Although surgical
      complications and functional status are recognized as independent factors for
      halting adjuvant therapy in patients that undergo pancreatic resections, other
      elements may play a role in deciding which patients get treated postoperatively.
      Here we determined demographic and clinical characteristics of patients receiving
      adjuvant chemotherapy, with the primary intent to investigate if age alone
      affects rates of adjuvant therapy. METHODS/MATERIALS: National Cancer Database
      (NCDB) was queried for patients that underwent surgery for pancreatic cancer.
      Groups were divided into: adjuvant chemotherapy (n=17,924) and no adjuvant
      chemotherapy (n=12,947). Basic demographics and treatment characteristics were
      analyzed. Age was compared with an independent means test; other comparisons used
      Chi-square test of independence. RESULTS: There was a statistical difference in
      age (adjuvant therapy 64.86+/-9.89 vs. no therapy 67.78+/-11.22, p<0.001),
      insurance type, facility type, and cancer stage for patients that received
      adjuvant therapy and those that did not. Average age of patients not receiving
      chemotherapy was significantly older at each pathologic stage. Subset analysis of
      patients treated with chemotherapy showed that the majority of patients received
      single agent regimens (62%), at an average of 59days following surgery, and at
      academic cancer programs (52%). CONCLUSIONS: Regardless of postoperative
      complications and functional status, age alone appears to affect rates of
      adjuvant therapy in patients with resected pancreatic cancer. Older patients
      should be offered tailored regimens that would allow them to complete the
      intended extent of treatment.

PMID- 29330040
TI  - YOD1 attenuates neurogenic proteotoxicity through its deubiquitinating activity.
AB  - Ubiquitination, a fundamental post-translational modification of intracellular
      proteins, is enzymatically reversed by deubiquitinase enzymes (deubiquitinases).
      >90 deubiquitinases have been identified. One of these enzymes, YOD1, possesses
      deubiquitinase activity and is similar to ovarian tumor domain-containing protein
      1, which is associated with regulation of the endoplasmic reticulum (ER)
      associated degradation pathway. Indeed, YOD1 is reported to be involved in the ER
      stress response induced by mislocalization of unfolded proteins in mammalian
      cells. However, it has remained unclear whether YOD1 is associated with
      pathophysiological conditions such as mitochondrial damage, impaired
      proteostasis, and neurodegeneration. We demonstrated that YOD1 possesses
      deubiquitinating activity and exhibits preference for K48- and K63-linked
      ubiquitin. Furthermore, YOD1 expression levels increased as a result of various
      stress conditions. We demonstrated that the neurogenic proteins that cause
      Huntington disease and Parkinson's disease induced upregulation of YOD1 level. We
      observed that YOD1 reduced disease cytotoxicity through efficient degradation of
      mutant proteins, whereas this activity was abolished by catalytically inactive
      YOD1. Additionally, YOD1 localized to Lewy bodies in Parkinson's disease
      patients. Collectively, these data suggest that the deubiquitinase YOD1
      contributes to pathogenesis of neurodegenerative disease by decreasing
      ubiquitination of abnormal proteins and their subsequent degradation.

PMID- 29330041
TI  - Acute epileptiform activity induced by gabazine involves proteasomal rather than
      lysosomal degradation of KCa2.2 channels.
AB  - Voltage-independent, Ca2+-activated K+ channels (KCa2.2, previously named SK2)
      are typically activated during a train of action potentials, and hence, are
      powerful regulators of cellular excitability by generating an
      afterhyperpolarizing potential (AHP) following prolonged excitation. In the acute
      in vitro epilepsy model induced in hippocampal brain slice preparations by
      exposure to the GABAA receptor blocker gabazine (GZ), the AHP was previously
      shown to be significantly decreased. Here, we asked the question whether KCa2.2
      protein degradation occurs in this model and which pathways are involved. To this
      end, we applied either gabazine alone or gabazine together with inhibitors of
      proteasomal and lysosomal protein degradation pathways, Z-Leu-Leu-Leu-CHO (MG132)
      and chloroquine (CQ), respectively. Western blot analysis showed a significant
      decrease of total KCa2.2 protein content in GZ-treated slices which could be
      rescued by concomitant incubation with MG132 and CQ. Using HEK293 cells
      transfected with a green fluorescent protein-tagged KCa2.2 construct, we
      demonstrated that proteasomal rather than lysosomal degradation was involved in
      KCa2.2 reduction. We then recorded epileptiform afterdischarges at hippocampal
      Schaffer collateral-CA1 synapses and confirmed that the GZ-induced increase was
      significantly attenuated by both MG132 and CQ, with MG132 being significantly
      more effective than CQ. Epileptiform afterdischarges were almost prevented by co
      application of protein degradation inhibitors. Furthermore, epileptiform
      afterdischarges could be re-established by using the KCa2.2 blocker UCL 1684
      suggesting involvement of KCa2.2. We conclude that in GZ-induced acute epilepsy,
      KCa2.2 degradation by proteasomal rather than lysosomal pathways plays a major
      role in the generation of epileptiform afterdischarges.

PMID- 29330043
TI  - HALT - A pause for anticoagulation consideration after bioprosthetic valves.

PMID- 29330042
TI  - Differences in the CT findings between vulnerable plaque and culprit lesions in
      acute coronary syndrome.
AB  - BACKGROUND: The CT finding of "vulnerable plaque" is widely regarded as similar
      to that of a culprit lesion in an acute coronary syndrome (ACS). However, this
      hypothesis may not be accurate, since "vulnerable plaques" may substantially
      change their morphology when they rupture to cause an ACS. METHODS: We
      retrospectively evaluated coronary CT angiography data sets of 25 patients with
      ACS who had vulnerable (n = 10) or culprit plaques (n = 15). We analyzed CT
      features including positive remodeling (PR), low attenuation plaque (LAP), the
      napkin ring sign (NRS), degree of stenosis (normal, <50%, 50-99%, 100%), and
      myocardial hypoperfusion in the left ventricle. RESULTS: There was no difference
      in the prevalence of PR, NRS, or LAP between vulnerable and culprit plaques. In
      contrast, a majority (80%, 8/10) of vulnerable plaques were associated with <50%
      luminal stenosis while total occlusion was identified in 47% (7/15) of culprit
      plaques (p = .037). In all patients with occlusion, myocardial hypoperfusion was
      demonstrated in the corresponding arterial territory on CT. CONCLUSION: CT
      features of vulnerable and culprit plaques differ in cases with thrombotic
      occlusion reflecting dynamic plaque changes related to the episode of ACS.

PMID- 29330044
TI  - Effects of acupuncture on the heart rate variability, cortisol levels and
      behavioural response induced by thunder sound in beagles.
AB  - Sound stimuli such as fireworks, firearms, and claps of thunder have been used as
      a stress reactivity model for dogs. Acupuncture has been widely used to treat and
      prevent physiological and behavioural disorders induced by stress. Our study aims
      to evaluate the effects of acupuncture on cardiac autonomic modulation (heart
      rate variability - HRV), behavioural (reactivity) and endocrine (cortisol levels)
      responses in dogs exposed to sounds of thunder. Twenty-four laboratory beagles
      (12 males and 12 females, 1-6years old) with no history of phobia to thunder were
      subjected to a sound stimulus that consisted of a standardized recording of
      thunder over a 150s period with a maximum intensity of 103-104dB. Before the
      sound, the dogs underwent a 20-minute session of needle insertion at acupuncture
      points Yintang, GV20, HT7, PC6 and ST36 (ACUP), in non-points (NP) or left
      undisturbed (CTL). Cardiac intervals were recorded using a frequency meter (RS
      800cx, Polar, Kempele, Finland) to evaluate the HRV, and the data were later
      analysed using CardioSeries v2.4.1 software. Acupuncture (ACUP) changed the
      sympathovagal balance with a shift towards parasympathetic modulation, reducing
      the prompt sound-induced increase in LF/HF (low frequency/high frequency) ratio
      and in the power of the LF band of the cardiac interval spectrum, and decreased
      the power of the HF band of the cardiac interval spectrum (p<0.05); however there
      was no change in the heart rate. Acupuncture reduced the behavioural response
      induced by sounds of thunder (when all behavioural parameters were considered
      together) and the behaviours hiding, restlessness, bolting and running around
      (when the parameters were analysed separately (p<0.05). There were no changes in
      cortisol levels due to the sound stimulus or acupuncture. Our results demonstrate
      that a session of acupuncture prior to sound stimulus can reduce cardiac
      autonomic and behavioural responses, without changing cortisol levels in beagles.

PMID- 29330045
TI  - Management of graves myopathy: Thyroid-associated orbitopathy: when should we
      operate?
AB  - Thyroid-associated orbitopathy (TAO) is an autoimmune disorder that affects
      multiple periocular tissues. In TAO, an active immunologic inflammatory phase is
      typically followed by a cicatrizing recovery phase. Management in the
      inflammatory phase is supportive, and surgical rehabilitation should generally be
      deferred until the patient is stable. We review current treatment concepts, with
      a focus on the timing and sequence of surgical procedures to address proptosis,
      motility restriction, and eyelid malposition in patients with TAO. A stepwise
      surgical approach maximizes the predictability of surgical outcomes and minimizes
      reoperations.

PMID- 29330046
TI  - Dermoid cysts: clinical predictors of complex lesions and surgical complications.

PMID- 29330047
TI  - An intrinsically disordered domain in Polaribacter irgensii KOPRI 22228 CspB
      confers extraordinary freeze-tolerance.
AB  - Organisms living in extremely cold environments possess mechanisms to survive low
      temperatures. Among the known cold-induced genes, cold-shock proteins (Csps) are
      the most prominent. A csp-homologous gene, cspBPi, has been cloned from the
      Arctic bacterium Polaribacter irgensii KOPRI 22228, and overexpression of this
      gene greatly increased the freezing tolerance of its host. This protein consists
      of a unique N-terminal domain and a well conserved C-terminal cold shock domain.
      To elucidate the detailed mechanisms involved in the extraordinary freeze
      tolerance conferred by CspBPi, we identified the responsible domain by mutational
      analysis. Changes of residues in the cold shock domain that are crucial for
      binding RNA or single-stranded DNA did not impair the ability of the host to
      survive freezing stress. All domain-shuffled CspBPi variants containing the N
      terminal domain retained the ability to confer superior freeze-tolerance. Slow
      electrophoretic mobility and far-UV circular dichroism spectra of the N-terminal
      domain suggested an intrinsically disordered structure for this region. The N
      terminal domain also bound to lipid vesicles in vitro. This lipid vesicle binding
      characteristic is shared with other intrinsically disordered proteins, such as
      alpha-synuclein and plant dehydrins, known to confer cold-tolerance when
      overexpressed, suggesting a mechanism for cold-survival through membrane binding.

PMID- 29330048
TI  - B cell activation in the cecal patches during the development of an experimental
      colitis model.
AB  - Although previous studies have suggested that appendix seems to be involved in
      the colitis, the role of this in the pathogenesis remains unclear. In this study,
      we assessed the importance of appendiceal lymphoid follicles, specifically the
      cecal patches (CP) in mice, using an experimental colitis model. Treatment with
      oxazolone resulted in ulcerations particularly at CP with follicular expansion as
      well as colitis. The colitis was attenuated by either appendectomy or the absence
      of mature B cells. We therefore established an intravital imaging system
      accompanied by the fluorescence resonance energy transfer technology to analyze
      the dynamic immune response of CP B cells. Our observation revealed frequent Ca2+
      signaling in CP B cells during the early phase of colitis development. These
      findings suggested that the CP B cells may be involved in the pathogenesis of
      colitis including inflammatory bowel diseases in humans.

PMID- 29330049
TI  - The histone demethylase PHF8 promotes adult acute lymphoblastic leukemia through
      interaction with the MEK/ERK signaling pathway.
AB  - Adult acute lymphoblastic leukemia (ALL) is a malignant disorder of lymphoid
      progenitor cells that is associated with a high risk of relapse and poor
      prognosis. Thus, novel pathogenic mechanisms and therapeutic targets need to be
      explored. Histone methylation is one of the most significant chromatin post
      translational modifications. Here, we show that the histone demethylase PHF8 is
      highly expressed in a large number of ALL clinical specimens and that PHF8
      expression is associated with ALL progression. PHF8 knockdown inhibits
      proliferation and promotes the apoptosis of ALL cells in vitro as well as
      attenuates tumor growth in vivo. PHF8 transcriptionally upregulates MEK1, a key
      molecule in the MEK/ERK pathway, at least partially by directly binding to its
      promoter, thereby activating the MEK/ERK pathway. In addition, we found that an
      inhibitor of the MEK/ERK pathway, PD184352, subsequently suppresses PHF8
      expression. Thus, PHF8 forms a positive feedback loop with the MEK/ERK pathway,
      and PHF8 knockdown enhances the lethality of PD184352 in ALL cells. In
      conclusion, this study identifies oncogenic functions of PHF8 in adult ALL and
      suggests a novel epigenetic strategy for disease intervention.

PMID- 29330050
TI  - Production and characterization of a novel site-specific-modifiable anti-OX40
      receptor single-chain variable fragment for targeted drug delivery.
AB  - OX40 receptor (tumor necrosis factor receptor superfamily, member 4; CD134) is a
      T-cell co-stimulatory molecule that plays an important role in T-cell activation
      and survival. OX40 receptor is activated by its ligand, OX40L; and modulation of
      the OX40-OX40L interaction is a promising target for the treatment of autoimmune
      diseases and cancers. Here, we generated a high-affinity anti-OX40 single-chain
      variable fragment carrying a C-terminal cysteine residue (scFvC). Physicochemical
      and functional analyses revealed that the scFvC bound to OX40-expressing cells
      and was internalized via OX40-mediated endocytosis without inducing
      phosphorylation of IkappaBalpha (nuclear factor of kappa light polypeptide gene
      enhancer in B-cells inhibitor, alpha), an important complex in the classical
      NFkappaB (nuclear factor kappa-light-chain-enhancer of activated B cells)
      signaling pathway. In addition, mutation of the 36th cysteine residue in variable
      region of light chain enabled site-specific chemical modification to carboxy
      terminal cysteine and improved the thermal stability of the scFvC. These results
      suggest that this novel high-affinity anti-OX40 scFvC may be useful as a
      transporter for targeted delivery of small compounds, proteins, peptides,
      liposomes, and nanoparticles, into OX40-expressing cells for the treatment of
      autoimmune diseases and cancers.

PMID- 29330051
TI  - Anti-tumor effects of triptolide on angiogenesis and cell apoptosis in
      osteosarcoma cells by inducing autophagy via repressing Wnt/beta-Catenin
      signaling.
AB  - Osteosarcoma is a common malignant bone tumor occurring in adolescents and
      children. The poor prognosis and low 5-year survival rate of osteosarcoma partly
      due to high metastasis of osteosarcoma. Triptolide (TPL), an extract from
      Tripterygium wilfordii, is widely used in cancer treatment. In our present study,
      we aimed to study the effect of TPL in osteosarcoma treatment and explore the
      associated regulation mechanism. Our study revealed that TPL inhibited
      angiogenesis by suppressing the expression of hypoxia inducible factor-1alpha
      (HIF-1alpha) and vascular endothelial growth factor (VEGF) in dose dependent
      manner. Besides, cell apoptosis was induced by TPL obviously in dose dependent
      manner. Further study demonstrated that TPL induced obvious cell autophagy with
      increased concentration. The cooperation of autophagy inhibitor 3-MA abolished
      the effect of TPL on anti-angiogenesis and apoptosis promoting. Moreover, we
      found that Wnt/beta-Catenin signaling was inactivated by TPL and the adding of
      pathway inducer Licl neutralized the effect of TPL on autophagy induction, anti
      angiogenesis and apoptosis promoting. Taken together, we suggested that TPL
      inhibited angiogenesis and induced cell apoptosis in osteosarcoma cells by
      inducing autophagy via repressing Wnt/beta-Catenin signaling.

PMID- 29330053
TI  - Clinical challenges of antimicrobial photodynamic therapy for bovine mastitis.

PMID- 29330052
TI  - ESCO2 knockdown inhibits cell proliferation and induces apoptosis in human
      gastric cancer cells.
AB  - Establishment of cohesion 1 homolog 2 (ESCO2), an essential gene for cohesion
      regulation and genomic stability, has not been studied in human gastric cancer
      (GC). We found that ESCO2 knockdown in human GC cell lines dramatically inhibited
      cell proliferation and induced cell apoptosis in vitro and suppressed tumor
      xenograft development in vivo. Furthermore, adenosine monophosphate-activated
      protein kinase (AMPK) was activated following the suppression of its downstream
      targets, including mammalian target of rapamycin (mTOR) and p70 ribosomal S6
      kinase 1 (p70S6K1), and this result was consistent with p53 activation.
      Significantly, co-immunoprecipitation (Co-IP) analyses indicated that ESCO2 can
      interact with p53 in GC cells. Taken together, our data demonstrate that ESCO2 is
      essential for the development of GC and might be a potential therapeutic target
      for treating GC.

PMID- 29330054
TI  - Deterministic stability regimes and noise-induced quasistable behavior in a pair
      of reciprocally inhibitory neurons.
AB  - Reciprocal inhibition is a common motif exploited by neuronal networks; an
      intuitive and tractable way to examine the behaviors produced by reciprocal
      inhibition is to consider a pair of neurons that synaptically inhibit each other
      and receive constant or noisy excitatory driving currents. In this work, we
      examine reciprocal inhibition using two models (a voltage-based and a current
      based integrate-and-fire model with instantaneous or temporally structured
      input), and we use analytic and computational tools to examine the bifurcations
      that occur and study the various possible monostable, bistable, and tristable
      regimes that can exist; we find that, depending on system parameters (and on
      choice of neuron model), there can exist up to 3 distinct monostable regimes
      (denoted M0, M1, M2), 3 distinct bistable regimes (denoted B, B1, B2), and a
      single tristable regime (denoted T). We also find that synaptic inhibition exerts
      independent control over the two neurons - inhibition from neuron 1 to neuron 2
      governs the spiking behavior of neuron 2 but has no impact on the spiking
      behavior of neuron 1 (and vice versa). The excitatory driving current, however,
      does not exhibit this property - the excitatory current to neuron 1 affects the
      spiking behavior of both neurons 1 and 2 (as does the excitatory current to
      neuron 2). Furthermore, we develop a methodology to examine the behavior of the
      system when the excitatory driving currents are allowed to be noisy, and we
      investigate the relationship between the behavior of the noisy system with the
      stability regime of the corresponding deterministic system.

PMID- 29330055
TI  - Tissue geometry may govern lung branching mode selection.
AB  - Lung branching morphogenesis proceeds in three stereotyped modes (domain, planar,
      and orthogonal branching). Much is known about the molecular players, including
      growth factors such as fibroblast growth factor 10 but it is unknown how these
      signals could actuate the different branching patterns. With the aim of
      identifying mechanisms that may determine the different branching modes, we
      developed a computational model of the epithelial lung bud and its surrounding
      mesenchyme. We studied transport of morphogens and localization of morphogen flux
      at lobe surfaces and lobe edges. We find that a single simple mechanism is
      theoretically capable of directing an epithelial tubule to elongate, bend,
      flatten, or bifurcate, depending solely on geometric ratios of the tissues in the
      vicinity of a growing tubule tip. Furthermore, the same simple mechanism is
      capable of generating orthogonal or planar branching, depending only on the same
      geometric ratios.

PMID- 29330056
TI  - Growth scaling for the early dynamics of HIV/AIDS epidemics in Brazil and the
      influence of socio-demographic factors.
AB  - The early dynamics of an infectious disease outbreak can be affected by various
      factors including the transmission mode of the disease and host-specific factors.
      While recent works have highlighted the presence of sub-exponential growth
      patterns during the early phase of epidemics, empirical studies examining the
      contribution of different factors to early epidemic growth dynamics are lacking.
      Here we aim to characterize and explain the early incidence growth patterns of
      local HIV/AIDS epidemics in Brazil as a function of socio-demographic factors.
      For this purpose, we accessed annual AIDS incidence series and state-level socio
      demographic variables from publicly available databases. To characterize the
      early growth dynamics of the HIV/AIDS epidemic, we employed the generalized
      growth model to estimate with quantified uncertainty the scaling of growth
      parameter (p) which captures growth patterns ranging from constant incidence
      (p=0) to sub-exponential (0 < p < 1) and exponential growth dynamics (p=1) at
      three spatial scales: national, regional, and state levels. We evaluated the
      relationship between socio-demographic variables and epidemic growth patterns
      across 27 Brazilian states using mixed-effect regression analyses. We found wide
      variation in the early dynamics of the AIDS epidemic in Brazil, displaying sub
      exponential growth patterns with the p parameter estimated substantially below
      1.0. The mean p was estimated to be 0.81 at the national level, with a range of
      0.72-0.85 at the regional level, and a range of 0.28-0.96 at the state level. Our
      findings support the notion that socio-demographic factors contribute to shaping
      the early growth dynamics of the epidemic at the local level. Gini index and
      socio-demographic index were negatively associated with the parameter p, whereas
      urbanicity was positively associated with p. The results could have theoretical
      significance in understanding differences in growth scaling across different
      sexually transmitted disease systems, and have public health implications to
      guide control.

PMID- 29330057
TI  - Fixation and absorption in a fluctuating environment.
AB  - A fundamental problem in the fields of population genetics, evolution, and
      community ecology, is the fate of a single mutant, or invader, introduced in a
      finite population of wild types. For a fixed-size community of N individuals,
      with Markovian, zero-sum dynamics driven by stochastic birth-death events, the
      mutant population eventually reaches either fixation or extinction. The classical
      analysis, provided by Kimura and his coworkers, is focused on the neutral case,
      [where the dynamics is only due to demographic stochasticity (drift)], and on
      time-independent selective forces (deleterious/beneficial mutation). However,
      both theoretical arguments and empirical analyses suggest that in many cases the
      selective forces fluctuate in time (temporal environmental stochasticity). Here
      we consider a generic model for a system with demographic noise and fluctuating
      selection. Our system is characterized by the time-averaged (log)-fitness s0 and
      zero-mean fitness fluctuations. These fluctuations, in turn, are parameterized by
      their amplitude gamma and their correlation time delta. We provide asymptotic
      (large N) formulas for the chance of fixation, the mean time to fixation and the
      mean time to absorption. Our expressions interpolate correctly between the
      constant selection limit gamma -> 0 and the time-averaged neutral case s0=0.

PMID- 29330058
TI  - Haptoglobin and serum amyloid A as putative biomarker candidates of naturally
      occurring bovine respiratory disease in dairy calves.
AB  - Bovine respiratory disease (BRD) is one of the leading causes of morbidity and
      mortality in dairy calves. Identification of reliable biomarkers of naturally
      occurring BRD is essential for ensuring early diagnosis and treatment of calves
      and monitoring treatment efficacy. This need is punctuated, especially in mild to
      moderate cases that would greatly help to decrease recurrence and the overall
      prevalence of BRD. The present study was conducted to investigate the changes in
      serum concentrations of haptoglobin (Hpt) and serum amyloid A (SAA) and
      association between oxidative stress and acute phase proteins (APPs) in BRD. Hpt
      and SAA levels significantly increased (P < .01) in BRD stressed calves as
      compared to healthy subjects. There was a significant decrease (P < .01) in serum
      albumin (Alb) concentration of infected calves as compared to controls. The
      oxidative stress markers revealed a significant (P < .01) increase in lipid
      peroxidation (LPO) and a concurrent decrease in activities of superoxide
      dismutase (SOD), reduced glutathione (R-GSH) and catalase (CAT) in BRD. A
      significant correlation among APPs, extent of oxidative stress and clinical score
      (CS) of calves was depicted. A stepwise decrease in Hpt and SAA and increase in
      Alb was observed in infected calves post-treatment. These results suggest
      implication of oxidative stress in enhancing APPs and monitoring of APPs as a
      potential complement to clinical assessment of treatment in calves with naturally
      occurring BRD. Hpt may be useful as the most sensitive biomarker in BRD. However,
      the combined use of Hpt and oxidative stress biomarkers would greatly improve the
      diagnostic accuracy.

PMID- 29330059
TI  - Biosynthesis, characterization and antimicrobial activities of zinc oxide
      nanoparticles from leaf extract of Glycosmis pentaphylla (Retz.) DC.
AB  - Biosynthesized nanoparticles have an incredible application in biomedicine owing
      to its simplicity, eco-friendly properties and low cost. The present study aims
      to determine the green synthesized zinc oxide nanoparticles from methanolic leaf
      extract of Glycosmis pentaphylla. The synthesized nanoparticles were
      characterized using UV-VIS Spectroscopy, Fluorescence spectrometer, FT-IR, XRD,
      SEM with EDAX and TEM. The confirmations of synthesized nanoparticles were
      characterized by peak at 351 and 410 nm in the UV-VIS spectrum and
      photoluminescence spectrum respectively. FT-IR studies revealed the functional
      group of the nanoparticles. The XRD data showed the crystalline nature of the
      nanoparticles and EDAX measurements indicated the 20.70% of highly pure zinc
      oxide metal. The morphological characterization of synthesized zinc oxide
      nanoparticles was analyzed by SEM and TEM and size of the particles were ranging
      from 32 to 36 nm. The synthesized zinc oxide nanoparticles exhibited interesting
      antimicrobial activity against pathogenic organisms. In addition, this is the
      first report on leaf mediated synthesis of zinc oxide (ZnO) nanoparticles from
      Glycosmis pentaphylla.

PMID- 29330060
TI  - Induction of innate immune response following introduction of infectious
      bronchitis virus (IBV) in the trachea and renal tissues of chickens.
AB  - Infectious bronchitis (IB) is a highly contagious respiratory disease of
      chickens, which is caused by the infectious bronchitis virus (IBV). The innate
      immune response is crucial for antiviral infections and revealing the pathogenic
      mechanisms of IBV. In this study, we presents an evaluation of interferon (I, II
      and III IFNs) in renal and tracheal samples from chickens experimentally infected
      previously vaccinated or not. The results suggest differential expression of
      chicken interferon, among them type I IFN elaborate a major role in fighting off
      virus. And vaccine confers greater induction ability of innate immunity thereby
      vaccination prior infection occurs might be necessary. Above all, we found that
      IFN-lambda also have an effect on IBV infection in trachea besides many other
      respiratory virus. This study provides the first comprehensive analysis of host
      virus interactions of IBV with chicken innate immune response mediated by
      interferon in various groups.

PMID- 29330061
TI  - Forsythoside A inhibited S. aureus stimulated inflammatory response in primary
      bovine mammary epithelial cells.
AB  - Forsythoside A (FTA), the major bioactive component extracted from Forsythiae
      fructus, has multiple biological properties especially anti-inflammatory
      property. Staphylococcus aureus (S. aureus), a Gram-positive organism, is one of
      most common pathogens that cause bovine mastitis. This study evaluated the anti
      inflammatory effect of FTA in S. aureus-stimulated primary bovine mammary
      epithelial cells (bMEC). Primary bovine mammary epithelial cells were isolated
      from the mammary tissue of lactating cows and identified as bMEC. The cell
      viability of bMEC was analyzed by MTT. The bMEC were stimulated with S. aureus in
      the presence or absence of FTA. Subsequently, the expression level of pro
      inflammatory cytokines was determined by quantitative real-time polymerase chain
      reaction (qRT-PCR). Nuclear factor-kappaB (NF-kappaB), inhibitor protein of NF
      kappaB (IkappaBalpha), p38, extracellular signal-regulated protein kinase (ERK),
      and c-JunN-terminal kinase (JNK) were measured by western blotting. The results
      showed that the cell viability was not affected by the FTA. FTA markedly down
      regulated the expressions of TNF-alpha, IL-1beta and IL-6 in S. aureus-stimulated
      bMEC. In addition, FTA was found to suppress S. aureus-induced NF-kappaB and
      MAPKs activation in a dose-dependent manner. These results indicated that FTA
      exerted anti-inflammatory property in S. aureus-stimulated bMEC by interfering
      the activation of NF-kappaB and MAPKs signaling pathways. Thereby, FTA may be a
      potential therapeutic agent against inflammatory disease.

PMID- 29330062
TI  - Fundus Densitometry Findings Suggest Optic Disc Hemorrhages in Primary Open-Angle
      Glaucoma Have an Arterial Origin.
AB  - PURPOSE: To analyze optic disc hemorrhages (DH) associated with primary open
      angle glaucoma by quantifying their geometric profile and comparing their
      densitometry with hemorrhages from retinal vein occlusions (RVO) and retinal
      macroaneurysms (MA), which have venous and arterial sources of bleeding,
      respectively. DESIGN: Retrospective cross-sectional study. METHODS: Setting:
      Massachusetts Eye & Ear. POPULATION: Fundus images of DH (n = 40), MA (n = 14),
      and RVO (n = 25) were identified. Patient clinical backgrounds and demographics
      were obtained. MAIN OUTCOME MEASURES: Grayscale pixel intensity units of
      hemorrhages and adjacent arteriole and venule over the same background tissue
      were measured. Densitometry differentials (arteriole or venule minus hemorrhage
      [DeltaA and DeltaV, respectively]) were calculated. The ratios of length (radial)
      to midpoint width for DH were calculated. Mean DeltaA and DeltaV between groups
      were compared with t tests. Multiple linear regression assessed the relation of
      retinal hemorrhage diagnosis to DeltaA and DeltaV and of DH shape to DeltaA and
      DeltaV. RESULTS: Mean (+/- standard deviation) DeltaA and DeltaV for DH (6.9 +/-
      7.1 and -4.7 +/- 8.0 pixel intensity units, respectively) and MA (5.3 +/- 5.9 and
      -6.0 +/- 4.6, respectively) were comparable (P >= .43). Mean DeltaA (14.6 +/-
      7.7) and DeltaV (6.4 +/- 6.3) for RVO were significantly higher compared to DH
      and MA (P < .0001) and remained significant in multivariable analyses. A unit
      increase in DH length-to-width ratio was associated with 1.2 (0.5) and 1.3 (0.5)
      pixel intensity unit (standard error) decrease in DeltaA and DeltaV, respectively
      (P <= .014). CONCLUSIONS: DH have densitometry profiles comparable to MA and
      different from RVO, suggesting that DH in glaucoma have an arterial origin.

PMID- 29330063
TI  - Risk of Ischemic Kidney Injury in Patients With Nonarteritic Anterior Ischemic
      Optic Neuropathy: A Nationwide Population-based Study.
AB  - PURPOSE: To investigate the risk of acute tubular necrosis (ATN) in patients with
      nonarteritic anterior ischemic optic neuropathy (NAION). DESIGN: Population-based
      cohort study. METHODS: This is a nationwide, population-based, retrospective
      study using data from the Korean national health claims database from 2011
      through 2015. Patients with NAION and randomly selected control subjects from the
      entire population of South Korea were enrolled. A log-rank analysis was used to
      evaluate a risk of ATN in the group of patients with NAION (study group) compared
      to an age-, sex-, and comorbidities-matched control group. Comorbidities included
      diabetes, chronic lung disease, congestive heart failure, ischemic stroke,
      anemia, septic shock, and antibiotic use. A Cox proportional hazards regression
      analysis with cluster effect was performed to calculate the adjusted hazard ratio
      (aHR) of ATN. RESULTS: A total of 22 498 patients were included in the study
      group and 31 475 in the control group. Twenty-six cases of ATN were observed in
      the NAION group and 11 in the control group. The study group was more likely to
      have ATN (aHR = 2.55, 95% confidence interval: 1.50-5.91, P = .029) than the
      control group. Among the 26 newly developed cases of ATN, 13 (50%) occurred in
      the 0-6 months before/after NAION. CONCLUSIONS: We demonstrated that subjects
      with NAION are at increased risk of ATN and suggested a possible common
      mechanistic link between the 2 diseases. These results provide significant
      evidence that proper patient education and further systemic evaluation of the
      possibility of ATN development are required in patients with NAION.

PMID- 29330065
TI  - Stargazin differentially modulates ampakine gating kinetics and pharmacology.
AB  - It was previously reported that Stargazin (STG) enhances the surface expression
      of AMPA receptors, controls receptor gating and slows channel desensitization as
      an auxiliary subunit of the receptors. Ampakines are a class of AMPA receptor
      positive allosteric modulators that modify rates of transmitter binding, channel
      activity and desensitization parameters. As such, they have shown efficacy in
      animal models of neurodegenerative diseases, where excitatory synaptic
      transmission is compromised. Given the functional similarities between STG and
      ampakines, the current study sought to probe interactions between STG and
      ampakine gating properties. The effects of the high impact ampakines, CX614 and
      cyclothiazide (CTZ), were compared with homomeric GluR1-flip (Glur1i) and GluR2
      flop (Glur2o) receptors expressed in HEK293 cells by transient transfection with
      or without STG gene. STG dramatically enhanced the surface expression of AMPA
      receptors and increased glutamate-induced steady-state currents during
      desensitization. STG also increased ratios of 500 MUM kainate and 500 MUM
      glutamate activated steady-state currents. STG reduced association rates of
      ampakines and differentially affected the dissociation rates for both CX614 and
      CTZ on desensitized receptors. The estimated Kd value for CX614 was lowered from
      340 MUM to 70 MUM, whereas that for CTZ was lowered from 170 MUM to 6 MUM by STG.
      The data suggest that Stargazin can dramatically alter the conformation of the
      receptor dimer interface where CX614 and CTZ are known to bind. This work also
      demonstrates the importance of considering STG interactions when developing
      ampakines to treat neurodegenerative diseases in which AMPAergic signaling is
      compromised.

PMID- 29330064
TI  - Antiplatelet and Anticoagulant Drugs Do Not Affect Visual Outcome in Neovascular
      Age-Related Macular Degeneration in the BRAMD Trial.
AB  - PURPOSE: To determine if use of antiplatelet or anticoagulant (AP/AC) medication
      influences visual acuity in patients with active neovascular age-related macular
      degeneration (N-AMD). DESIGN: Retrospective analysis of data from a randomized
      controlled trial. METHODS: Setting: Multicenter. STUDY POPULATION: Total of 330
      patients with active N-AMD from the BRAMD study, a comparative trial between
      bevacizumab and ranibizumab in the Netherlands. OBSERVATION PROCEDURES: Patients
      underwent an extensive ophthalmic examination. Visual acuity was categorized into
      functional vision (best-corrected visual acuity [BCVA] >= 0.5), visual impairment
      (BCVA < 0.5), and severe visual impairment (BCVA < 0.3). Fundus photographs were
      graded for presence of retinal or subretinal hemorrhages. Information on AP/AC
      medication was obtained through interview. Logistic regression analysis was used
      to determine associations between AP/AC medication and outcomes. Frequency of
      hemorrhages in users and non-users stratified for visual acuity categories was
      analyzed with ANCOVA. MAIN OUTCOME MEASURES: BCVA and presence of hemorrhages.
      RESULTS: In total, 40.9% of the patients used AP/AC medication, of which 73.3%
      was aspirin. AP/AC use was not associated with visual impairment (adjusted odds
      ratio [OR] 0.79; 95% confidence interval [CI] 0.43-1.44) or severe visual
      impairment (adjusted OR 0.75; 95% CI 0.40-1.43). Patients on AP/AC presented with
      comparable frequencies of hemorrhages (27% vs 32%, P = .32, respectively).
      Similar results were found when analyses were restricted to aspirin users only.
      CONCLUSION: In our study, use of AP/AC medication was associated neither with
      visual decline nor with the occurrence of hemorrhages in patients with active N
      AMD.

PMID- 29330067
TI  - Protein complexes as psychiatric and neurological drug targets.
AB  - The need for improved medications for psychiatric and neurological disorders is
      clear. Difficulties in finding such drugs demands that all strategic means be
      utilized for their invention. The discovery of forebrain specific AMPA receptor
      antagonists, which selectively block the specific combinations of principal and
      auxiliary subunits present in forebrain regions but spare targets in the
      cerebellum, was recently disclosed. This discovery raised the possibility that
      other auxiliary protein systems could be utilized to help identify new medicines.
      Discussion of the TARP-dependent AMPA receptor antagonists has been presented
      elsewhere. Here we review the diversity of protein complexes of neurotransmitter
      receptors in the nervous system to highlight the broad range of protein/protein
      drug targets. We briefly outline the structural basis of protein complexes as
      drug targets for G-protein-coupled receptors, voltage-gated ion channels, and
      ligand-gated ion channels. This review highlights heterodimers, subunit-specific
      receptor constructions, multiple signaling pathways, and auxiliary proteins with
      an emphasis on the later. We conclude that the use of auxiliary proteins in
      chemical compound screening could enhance the detection of specific, targeted
      drug searches and lead to novel and improved medicines for psychiatric and
      neurological disorders.

PMID- 29330068
TI  - Engineering of hydroxymandelate synthases and the aromatic amino acid pathway
      enables de novo biosynthesis of mandelic and 4-hydroxymandelic acid with
      Saccharomyces cerevisiae.
AB  - Mandelic acid (MA) and 4-hydroxymandelic acid (HMA) are valuable specialty
      chemicals used as precursors for flavors as well as for cosmetic and
      pharmaceutical purposes. Today they are mainly synthesized chemically. Their
      synthesis through microbial fermentation would allow for environmentally
      sustainable production. In this work, we engineered the yeast Saccharomyces
      cerevisiae for high-level production of MA and HMA. Expressing the
      hydroxymandelate synthase from Amycolatopsis orientalis in a yeast wild type
      strain resulted in the production of 119mg/L HMA from glucose. As the enzyme also
      accepts phenylpyruvate as a substrate aside from its native substrate 4
      hydroxyphenylpyruvate, 0.7mg/L MA was also produced. Preventing binding of 4
      hydroxyphenylpyruvate to the hydroxymandelate synthase by introducing a S201V
      replacement in its substrate binding site nearly completely prevented HMA
      production but increased MA production only 3.5-fold. To further increase HMA and
      MA production, the aromatic amino acid pathway was engineered. We increased the
      precursor supply by introducing modifications in the shikimic acid pathway
      (ARO1?, ARO3K222L?, ARO4K220L?) and reducing flux into the Ehrlich pathway
      (aro10Delta), and thereby enhanced the HMA titer to 465mg/L and the MA titer to
      2.9mg/L. A further increase in HMA and MA titers was achieved by replacing the
      hydroxymandelate synthase from A. orientalis with the corresponding enzyme from
      Nocardia uniformis. Subsequently, we introduced additional deletions to block the
      competing tryptophan branch (trp2Delta), to further decrease flux into the
      Ehrlich pathway (pdc5Delta) and to avoid transamination of phenylpyruvate and 4
      hydroxyphenylpyruvate (aro8Delta, aro9Delta). We achieved more than 1g/L 4
      hydroxymandelate when additionally preventing formation of phenylpyruvate by
      deleting PHA2. When deleting TYR1 to prevent formation of 4-hydroxyphenylpyruvate
      instead, an MA titer of 236mg/L was achieved. This is a more than 200-fold
      increase in MA production compared to the wild type strain expressing the
      hydroxymandelate synthase from A. orientalis. Finally, we showed that S.
      cerevisiae tolerates HMA and MA to concentrations as high as 3g/L and 7.5g/L,
      respectively. Our results demonstrate that S. cerevisiae is a promising host for
      sustainable MA and HMA production.

PMID- 29330070
TI  - Neutropenia as a Complication of Tumefactive Demyelinating Disease: A Case
      Report.
AB  - : Tumefactive demyelination is an aggressive, localized, generally solitary area
      of demyelination that often mimics a neoplasm. We present a case of a 13-year-old
      female patient who presented with sudden-onset progressive hemiplegia and
      hemianopsia. Magnetic resonance imaging of the brain showed tumefactive
      demyelination with partial rim of enhancement. During inpatient rehabilitation,
      she developed myalgias, rash, and abdominal and mouth pain with evidence for
      severe neutropenia. The neutropenia was determined to be a secondary complication
      of the tumefactive disease process. This scenario may be concerning in an
      inpatient rehabilitation setting, as patients share common areas, increasing the
      risk of acquired infection while neutropenic. LEVEL OF EVIDENCE: V.

PMID- 29330069
TI  - Conformation and Trimer Association of the Transmembrane Domain of the
      Parainfluenza Virus Fusion Protein in Lipid Bilayers from Solid-State NMR:
      Insights into the Sequence Determinants of Trimer Structure and Fusion Activity.
AB  - Enveloped viruses enter cells by using their fusion proteins to merge the virus
      lipid envelope and the cell membrane. While crystal structures of the water
      soluble ectodomains of many viral fusion proteins have been determined, the
      structure and assembly of the C-terminal transmembrane domain (TMD) remains
      poorly understood. Here we use solid-state NMR to determine the backbone
      conformation and oligomeric structure of the TMD of the parainfluenza virus 5
      fusion protein. 13C chemical shifts indicate that the central leucine-rich
      segment of the TMD is alpha-helical in POPC/cholesterol membranes and POPE
      membranes, while the Ile- and Val-rich termini shift to the beta-strand
      conformation in the POPE membrane. Importantly, lipid mixing assays indicate that
      the TMD is more fusogenic in the POPE membrane than in the POPC/cholesterol
      membrane, indicating that the beta-strand conformation is important for fusion by
      inducing membrane curvature. Incorporation of para-fluorinated Phe at three
      positions of the alpha-helical core allowed us to measure interhelical distances
      using 19F spin diffusion NMR. The data indicate that, at peptide:lipid molar
      ratios of ~1:15, the TMD forms a trimeric helical bundle with inter-helical
      distances of 8.2-8.4A for L493F and L504F and 10.5A for L500F. These data provide
      high-resolution evidence of trimer formation of a viral fusion protein TMD in
      phospholipid bilayers, and indicate that the parainfluenza virus 5 fusion protein
      TMD harbors two functions: the central alpha-helical core is the trimerization
      unit of the protein, while the two termini are responsible for inducing membrane
      curvature by transitioning to a beta-sheet conformation.

PMID- 29330071
TI  - OnabotulinumtoxinA for the Treatment of Poststroke Distal Lower Limb Spasticity:
      A Randomized Trial.
AB  - BACKGROUND: Poststroke distal lower limb spasticity impairs mobility, limiting
      activities of daily living and requiring additional caregiver time. OBJECTIVE: To
      evaluate the efficacy, safety, and sustained benefit of onabotulinumtoxinA in
      adults with poststroke lower limb spasticity (PSLLS). DESIGN: A multicenter,
      randomized, double-blind, phase 3, placebo-controlled trial (NCT01575054).
      SETTING: Sixty study centers across North America, Europe, Russia, the United
      Kingdom, and South Korea. PATIENTS: Adult patients (18-65 years of age) with
      PSLLS (Modified Ashworth Scale [MAS] >=3) of the ankle plantar flexors and the
      most recent stroke >=3 months before study enrollment. INTERVENTIONS: During the
      open-label phase, patients received <=3 onabotulinumtoxinA treatments (<=400 U)
      or placebo at approximately 12-week intervals. Treatments were into the ankle
      plantar flexors (onabotulinumtoxinA 300 U into ankle plantar flexors; <=100 U,
      optional lower limb muscles). MAIN OUTCOME MEASUREMENTS: The double-blind primary
      endpoint was MAS change from baseline (average score at weeks 4 and 6). Secondary
      measures included physician-assessed Clinical Global Impression of Change (CGI),
      MAS change from baseline in optional muscles, Goal Attainment Scale (GAS), and
      pain scale. RESULTS: Of 468 patients enrolled, 450 (96%) completed the double
      blind phase and 413 (88%) completed the study. Small improvements in MAS observed
      with onabotulinumtoxinA during the double-blind phase (onabotulinumtoxinA, -0.8;
      placebo, -0.6, P = .01) were further enhanced with additional treatments through
      week 6 of the third open-label treatment cycle
      (onabotulinumtoxinA/onabotulinumtoxinA, -1.2; placebo/onabotulinumtoxinA, -1.4).
      Small improvements in CGI observed during the double-blind phase
      (onabotulinumtoxinA, 0.9; placebo, 0.7, P = .01) were also further enhanced
      through week 6 of the third open-label treatment cycle
      (onabotulinumtoxinA/onabotulinumtoxinA, 1.6; placebo/onabotulinumtoxinA, 1.6).
      Physician- and patient-assessed GAS scores improved with each subsequent
      treatment. No new safety signals emerged. CONCLUSIONS: OnabotulinumtoxinA
      significantly improved ankle MAS, CGI, and GAS scores compared with placebo;
      improvements were consistent and increased with repeated treatments of
      onabotulinumtoxinA over 1 year in patients with PSLLS. LEVEL OF EVIDENCE: I.

PMID- 29330072
TI  - Chronic Thigh Pain in a Young Adult Diagnosed as Synovial Sarcoma: A Case Report.
AB  - : Synovial sarcoma is a slow-growing, intermediate- to high-grade neoplasm with
      extensive metastatic potential. Accurate diagnosis of synovial sarcoma may pose a
      challenge to providers because of its indolent growth and variable presentation.
      The findings of a soft-tissue, periarticular mass with calcifications in a young
      patient are highly suggestive of synovial sarcoma. Although different imaging
      modalities can aid in the diagnosis of synovial sarcoma, diagnostic certainty is
      typically only confirmed by biopsy and histologic analysis. We present a case
      describing the diagnostic workup of synovial sarcoma with an emphasis on imaging
      findings in a patient with increasing symptomatology spanning more than a decade.
      LEVEL OF EVIDENCE: V.

PMID- 29330074
TI  - A nonlinear continuous-time model for a semelparous species.
AB  - Periodical semelparous insects such as cicadas and May beetles exhibit
      synchronization in age classes such that only one age class is present at any
      point of time. This leads to outbreaks of adults as they all reach maturity
      around the same time. Discrete-time models of semelparous species have shown that
      this type of synchronous cycling can occur as a result of greater between-class
      competition relative to within-class competition. However, relatively few studies
      have examined continuous-time models of semelparous species. Here we develop a
      continuous-time model for a semelparous species using a technique called the
      linear chain trick to convert a non-linear McKendrick partial differential
      equation into a finite system of ordinary differential equations. We represent
      semelparity by a birth function whose age distribution can be made arbitrarily
      narrow. We show that a Hopf bifurcation may occur in this model as a result of
      competition between reproducing and non-reproducing classes. This bifurcation
      leads to stable cycles in which the two classes are out of phase, thus providing
      a continuous-time counterpart to the synchronous cycles that occur in discrete
      time models.

PMID- 29330073
TI  - The Association of Clinic-Based Mobility Tasks and Measures of Community
      Performance and Risk.
AB  - INTRODUCTION: Gait speed is recognized as an important predictor of adverse
      outcomes in older people. However, it is unknown whether other more complex
      mobility tasks are better predictors of such outcomes. OBJECTIVE: To examine a
      range of clinic-based mobility tests and determine which were most strongly
      associated with measures of community performance and risk (CP&R). DESIGN: Cross
      sectional study. SETTING: Central Control Mobility and Aging Study, Westchester
      County, New York. PARTICIPANTS: Aged >=65 years (n = 424). METHODS: Clinic-based
      mobility measures included gait speed measured during normal and dual-task
      conditions, the Floor Maze Immediate and Delay tasks, and stair ascending and
      descending. CP&R measures were self-reported by the use of standardized
      questionnaires and classified into measures of performance (distance walked,
      travel outside one's home [life space], activities of daily living, and
      participation in cognitive leisure activities) or risk (balance confidence, fear
      of falling, and past falls). Linear and logistic regression were used to examine
      associations between the clinic-based mobility measures and CP&R measures
      adjusting for covariates. RESULTS: The mean age of the sample was 77.8 (SD 6.4)
      years, and 55.2% (n = 234) were female. In final models, faster normal walking
      speed was most strongly associated with 5 of the 7 community measures (greater
      distance walked, greater life space, better activities of daily living function,
      higher balance confidence, and less fear of falling; all P < .05). More complex
      tasks (walking while talking and maze immediate) were associated with cognitive
      leisure activity (P < .05), and ascending stairs was the only measure associated
      with a history of falls (P < .05). CONCLUSION: Normal walking speed is a simple
      and inexpensive clinic-based mobility test that is associated with a wide range
      of CP&R measures. In addition, poorer performance ascending stairs may assist in
      identifying those at risk of falls. Poorer performance in more complex mobility
      tasks (walking while talking and maze immediate) may suggest inability to
      participate in cognitive leisure activities. LEVEL OF EVIDENCE: III.

PMID- 29330066
TI  - Regulation of vascular tone homeostasis by NO and H2S: Implications in
      hypertension.
AB  - Nitric oxide (NO) and hydrogen sulfide (H2S) are two gasotransmitters that are
      produced in the vasculature and contribute to the regulation of vascular tone. NO
      and H2S are synthesized in both vascular smooth muscle and endothelial cells; NO
      functions primarily through the sGC/cGMP pathway, and H2S mainly through
      activation of the ATP-dependent potassium channels; both leading to relaxation of
      vascular smooth muscle cells. A deficit in the NO/H2S homeostasis is involved in
      the pathogenesis of various cardiovascular diseases, especially hypertension. It
      is now becoming increasingly clear that there are important interactions between
      NO and H2S and that have a profound impact on vascular tone and this may provide
      insights into the new therapeutic interventions. The aim of this review is to
      provide a better understanding of individual and interactive roles of NO and H2S
      in vascular biology. Overall, available data indicate that both NO and H2S
      contribute to vascular (patho)physiology and in regulating blood pressure. In
      addition, boosting NO and H2S using various dietary sources or donors could be a
      hopeful therapeutic strategy in the management of hypertension.

PMID- 29330075
TI  - The epidemic model based on the approximation for third-order motifs on networks.
AB  - The spread of an infectious disease may depend on the structure of the network.
      To study the influence of the structure parameters of the network on the spread
      of the epidemic, we need to put these parameters into the epidemic model. The
      method of moment closure introduces structure parameters into the epidemic model.
      In this paper, we present a new moment closure epidemic model based on the
      approximation of third-order motifs in networks. The order of a motif defined in
      this paper is determined by the number of the edges in the motif, rather than by
      the number of nodes in the motif as defined in the literature. We provide a
      general approach to deriving a set of ordinary differential equations that
      describes, to a high degree of accuracy, the spread of an infectious disease.
      Using this method, we establish a susceptible-infected-recovered (SIR) model. We
      then calculate the basic reproduction number of the SIR model, and find that it
      decreases as the clustering coefficient increases. Finally, we perform some
      simulations using the proposed model to study the influence of the clustering
      coefficient on the final epidemic size, the maximum number of infected, and the
      peak time of the disease. The numerical simulations based on the SIR model in
      this paper fit the stochastic simulations based on the Monte Carlo method well at
      different levels of clustering. Our results show that the clustering coefficient
      poses impediments to the spread of disease under an SIR model.

PMID- 29330076
TI  - Frontoethmoidal Schwannoma with Exertional Cerebrospinal Fluid Rhinorrhea: Case
      Report and Review of Literature.
AB  - BACKGROUND: Frontoethmoidal schwannomas are rare. No case manifesting exertional
      cerebrospinal fluid (CSF) rhinorrhea has ever been reported to the best of our
      knowledge. CASE DESCRIPTION: In this report, we describe an extremely rare case
      of frontoethmoidal schwannoma extending through the olfactory groove with
      exertional CSF rhinorrhea as the initial symptom. A 50-year-old woman was
      presented to our clinic for frequent nasal discharge on exertion. A postcontrast
      computed tomographic scan demonstrated heterogeneously enhanced tumor from the
      anterior cranial fossa to the anterior ethmoid sinus. A gadolinium-enhanced T1
      weighted magnetic resonance image revealed a well-defined heterogeneously
      enhanced tumor situated in the midline anterior cranial fossa and anterior
      ethmoid sinus. After the resection, the defect of the right anterior skull base
      was reconstructed with a fascia graft and adipose tissue taken from the abdomen,
      as well as a pedicle periosteum flap. A histologic examination revealed the tumor
      as schwannoma. Her rhinorrhea completely resolved. She regained her sense of
      smell and taste 1 month after the operation. CONCLUSION: According to previous
      reports, olfactory groove, and paraolfactory groove/periolfactory groove
      schwannomas can be divided into 4 types: subfrontal, nasoethmoidal,
      frontoethmoidal, and ethmofrontal. Among them, a frontoethmoidal schwannoma can
      manifest exertional CSF rhinorrhea as an initial symptom.

PMID- 29330078
TI  - Intraoperative Flow Cytometry Enables the Differentiation of Primary Central
      Nervous System Lymphoma from Glioblastoma.
AB  - OBJECTIVE: Accurate preoperative and intraoperative differentiation between
      primary central nervous system lymphoma (PCNSL) and glioblastoma (GBM) is
      sometimes difficult. Distinguishing between these tumors during surgery is
      important because surgical treatment is different between the 2 tumors. In this
      study, we established a new method of intraoperative differentiation between
      PCNSL and GBM using intraoperative flow cytometry (iFC), and we retrospectively
      tested whether iFC was useful for the intraoperative diagnosis of PCNSL and GBM.
      METHODS: We analyzed the iFC data of 250 patients (28 with PCNSL and 222 with
      GBM) and then evaluated aneuploidy and S-phase population. RESULTS: Aneuploidy
      was detected in 54.5% of GBM cases but in only 7.14% of PCNSL cases. Aneuploidy
      indicated GBM, but it was difficult to distinguish PCNSL from GBM when a tumor
      had a diploid pattern. Thus, for tumors without aneuploidy, we evaluated the S
      phase population: S2, the ratio of the average height of the S-phase to the
      height of the diploid peak. S2 was significantly higher in PCNSL than in GBM.
      Based on these results, we established an algorithm for differentiating between
      PCNSL and GBM using DNA aneuploidy and S2. Comparing this new iFC algorithm and
      the permanent pathologic diagnosis, the sensitivity was 89.3%, the specificity
      was 93.7%, and the accuracy was 93.2%. CONCLUSIONS: iFC is useful for the
      intraoperative differentiation between PCNSL and GBM and it aids in
      intraoperative decision making within a short time. The accuracy of
      intraoperative diagnosis of these tumors seems to be higher with the combination
      of iFC and intraoperative rapid pathologic diagnosis.

PMID- 29330077
TI  - Blood Ethanol Levels Are Not Related to Coagulation Changes, as Measured by
      Thromboelastography, in Traumatic Brain Injury Patients.
AB  - BACKGROUND: Brain injury is a leading cause of death and disability in trauma
      patients. Ethanol (EtOH) use near the time of injury may contribute to worse
      outcomes in these patients by exacerbating coagulopathy. There are limited data
      regarding the effects of EtOH on coagulation and progression of traumatic
      intracranial hemorrhage (TICH). METHODS: We performed a retrospective analysis of
      a prospective observational study of 168 trauma patients with TBI at an urban
      level 1 trauma center. Thromboelastography (TEG) was performed on admission and
      over the subsequent 48 hours. Demographic, physiologic, and outcomes data were
      collected. Computed tomography imaging of the head performed within the first 48
      hours of admission was analyzed for progression of TICH. RESULTS: Thirty-six
      percent of patients (n = 61) had positive blood EtOH on admission (median EtOH
      level = 198 mg/dL [range, 16-376 mg/dL]). EtOH-positive patients were less
      severely injured than EtOH-negative patients (P = 0.01). Other admission
      demographic and physiologic variables were similar between groups. There were no
      significant differences in TEG values between EtOH-positive and EtOH-negative
      patients on admission or during the subsequent 48 hours. There were no
      differences in radiographic progression of hemorrhage, the need for neurosurgical
      procedure, or mortality between EtOH-positive and EtOH-negative patients.
      CONCLUSIONS: EtOH use near the time of traumatic injury was not associated with
      alterations in coagulation, as measured by traditional coagulation tests or by
      TEG, in patients with TICH. Furthermore, a positive blood alcohol at admission
      was not associated with increased mortality or need for neurosurgical procedure
      these patients.

PMID- 29330079
TI  - Impact of Platelet Transfusion on Intracerebral Hemorrhage in Patients on
      Antiplatelet Therapy-An Analysis Based on Intracerebral Hemorrhage Score.
AB  - OBJECTIVE: Platelet transfusions for patients with intracerebral hemorrhage (ICH)
      on antiplatelet therapy (APT) remain controversial. Diverging past research and
      differences in platelet preparation warrant further investigation of this topic.
      In this study, the association between platelet transfusion and clinical outcomes
      of ICH is investigated in patients matched by ICH score, a validated predictor of
      mortality. METHODS: A consecutive review of all patients from 2012 to 2015 with
      nontraumatic ICH was performed. Risk factors including demographics, medical
      comorbidities, APT use, and ICH score were reviewed. Standardized differences
      were used to assess baseline characteristics; logistic regression models were
      performed to determine whether platelet transfusions were associated with adverse
      outcomes, both before and after matching for ICH score. RESULTS: A total of 538
      patients with nontraumatic ICH were investigated. Of these, 168 were on APT; 71
      were excluded. Thirty-nine patients (40%) received platelet transfusions and 58
      (60%) did not. An overall mortality of 9.3% was measured, with 29.9% of patients
      enduring complications. In the unmatched cohort, patients who received platelet
      transfusions were more likely to deteriorate (odds ratio [OR], 4.7), undergo
      surgical intervention during their hospital stay (OR, 7.2), be discharged with a
      worse modified Rankin Scale score (OR, 3.6), or die (OR, 6.1). After matching by
      ICH score, platelet transfusion was not a significant predictor for any negative
      outcome. CONCLUSIONS: This is the first analysis of platelet transfusions in
      patients with ICH based on ICH score. For patients on APT, platelet transfusion
      is not associated with clinical outcomes in an ICH score-matched sample.

PMID- 29330080
TI  - Use of Pulsed Radiofrequency Energy Device (PEAK Plasmablade) in Neuromodulation
      Implant Revisions.
AB  - BACKGROUND: Battery replacement or revision surgery for neuromodulation implants
      is conventionally performed using sharp dissection. Meticulous dissection within
      thick scar tissue is vital to avoid damage to surrounding lead(s), which could
      result in more extensive revision surgery. Traditional electrosurgery devices are
      contraindicated as the emitted energy can be transferred to the hardware,
      resulting in implant or tissue damage with severe consequent complications.
      OBJECTIVE: We report our experience and potential applications of a novel, pulsed
      monopolar radiofrequency energy device (PEAK PlasmaBlade, Medtronic PLC,
      Minneapolis, Minnesota, USA), which facilitates dissection around implants
      without the risk of damaging or transmitting energy through the system. METHODS:
      We conducted a 2-center retrospective study to review the indications, safety,
      and efficacy of the PlasmaBlade in 57 cases requiring either neuromodulation
      system replacement or revision. Deep brain stimulator (DBS) battery replacements
      were undertaken in 45 cases, 8 vagal nerve stimulator battery revisions, 2
      intrathecal baclofen system revision, 1 DBS extension revision, and 1 DBS scar
      revision around the cranial portion of the lead. RESULTS: All cases proceeded
      without adverse event or damage to lead/generator and with a subjective and
      objective impression of significant time savings. Average operating times for
      battery replacements were reduced from 37 to 26 minutes (P = 0.015). CONCLUSION:
      In our experience, the PlasmaBlade is safe to use in revising/replacing
      neuromodulation implants. We observed no damage or transmission of energy to the
      implants or leads; additional advantages of the system include reduced operating
      times, less damage to surrounding tissue, and the potential to facilitate
      revision procedures in awake patients under local anesthesia.

PMID- 29330082
TI  - Clinical trials recruitment planning: A proposed framework from the Clinical
      Trials Transformation Initiative.
AB  - Patient recruitment is widely recognized as a key determinant of success for
      clinical trials. Yet a substantial number of trials fail to reach recruitment
      goals-a situation that has important scientific, financial, ethical, and policy
      implications. Further, there are important effects on stakeholders who directly
      contribute to the trial including investigators, sponsors, and study
      participants. Despite efforts over multiple decades to identify and address
      barriers, recruitment challenges persist. To advance a more comprehensive
      approach to trial recruitment, the Clinical Trials Transformation Initiative
      (CTTI) convened a project team to examine the challenges and to issue actionable,
      evidence-based recommendations for improving recruitment planning that extend
      beyond common study-specific strategies. We describe our multi-stakeholder effort
      to develop a framework that delineates three areas essential to strategic
      recruitment planning efforts: (1) trial design and protocol development, (2)
      trial feasibility and site selection, and (3) communication. Our recommendations
      propose an upstream approach to recruitment planning that has the potential to
      produce greater impact and reduce downstream barriers. Additionally, we offer
      tools to help facilitate adoption of the recommendations. We hope that our
      framework and recommendations will serve as a guide for initial efforts in
      clinical trial recruitment planning irrespective of disease or intervention
      focus, provide a common basis for discussions in this area and generate targets
      for further analysis and continual improvement.

PMID- 29330081
TI  - Optimization of a technology-supported physical activity intervention for breast
      cancer survivors: Fit2Thrive study protocol.
AB  - Fit2Thrive is a theory-guided physical activity promotion trial using the
      Multiphase Optimization Strategy (MOST) to test efficacy for improving physical
      activity of five technology-supported physical activity promotion intervention
      components among breast cancer survivors. This trial will recruit 256 inactive
      breast cancer survivors nationwide. All participants will receive the core
      intervention which includes a Fitbit and standard self-monitoring Fit2Thrive
      smartphone application which will be downloaded to their personal phone. Women
      will be randomized to one of 32 conditions in a factorial design involving five
      factors with two levels: support calls (No vs. Yes), app type (standard vs.
      deluxe), text messaging (No vs. Yes), online gym (No vs. Yes) and Fitbit Buddy
      (No vs. Yes). The proposed trial examines the effects of the components on
      physical activity at 12 and 24weeks. Results will support the selection of a
      final package of intervention components that has been optimized to maximize
      physical activity and is subject to an upper limit of cost. The optimized
      intervention will be tested in a future trial. Fit2Thrive is the first trial to
      use the MOST framework to develop and test a physical activity promotion
      intervention in breast cancer survivors and will lead to an improved
      understanding of how to effectively change survivors' physical activity. These
      findings could result in more scalable, effective physical activity interventions
      for breast cancer survivors, and, ultimately, improve health and disease
      outcomes.

PMID- 29330083
TI  - Rationale and design of the Clinic and Community Approaches to Healthy Weight
      Randomized Trial.
AB  - BACKGROUND: Recent studies have demonstrated the effectiveness of family
      centered, pediatric weight management programs in reducing childhood obesity.
      Yet, programs to optimize the care of low-income children with obesity are
      needed. We sought to examine the comparative effectiveness of two, potentially
      scalable pediatric weight management programs delivered to low-income children in
      a clinical or community setting. MATERIALS AND METHODS: The Clinic and Community
      Approaches to Healthy Weight Trial is a randomized trial in two communities in
      Massachusetts that serve a large population of low-income children and families.
      The two-arm trial compares the effects of a pediatric weight management program
      delivered in the Healthy Weight Clinics of two federally qualified health centers
      (FQHC) to the Healthy Weight and Your Child programs delivered in two YMCAs.
      Eligible children are 6 to 12 years old with a body mass index (BMI) >= 85th
      percentile seen in primary care at the two FQHCs. Both programs are one-year in
      duration and have at least 30 contact hours throughout the year. Measures are
      collected at baseline, 6 months, and 1 year. The main outcome is 1-year change in
      BMI (kg/m2) and percent change of the 95th percentile (%BMIp95). CONCLUSION: The
      Clinic and Community Approaches to Healthy Weight Trial seeks to 1) examine the
      comparative effects of a clinical and community based intervention in improving
      childhood obesity, and 2) inform the care of >7 million children with obesity
      covered by the Children's Health Insurance Program or Medicaid.

PMID- 29330084
TI  - Real-time reverse transcription recombinase polymerase amplification assay for
      rapid detection of porcine epidemic diarrhea virus.
AB  - Porcine epidemic diarrhea (PED), which is caused by porcine epidemic diarrhea
      virus (PEDV), is an acute, highly contagious enteric disease characterized by
      severe watery diarrhea, vomiting, dehydration, and high mortality in suckling
      piglets. A real-time reverse-transcription recombinase polymerase amplification
      assay (RT-RPA) was developed based on the nucleocapsid gene of PEDV. RT-RPA assay
      was performed at 40  degrees C for 20 min. The assay could detect both the
      classical and variant PEDV strains, and there was no cross-reaction with other
      pathogens tested. Using the in vitro transcribed PEDV RNA as template, the
      analytical sensitivity was 23 copies per reaction. The assay performance was
      evaluated by testing 76 clinical samples. PEDV RNA positive rate was 55.3%
      (42/76) by RT-RPA and 59.2% (45/76) by real-time RT-PCR. The diagnostic agreement
      between the two assays was 96.1% (73/76), and the R2 value of the two assays was
      0.903 by linear regression analysis. The developed RT-RPA assay provides a useful
      alternative tool for simple, rapid and reliable detection of PEDV in resource
      limited diagnostic laboratories and on-site facilities.

PMID- 29330086
TI  - Learning profitable habitat types by juvenile crayfish.
AB  - Habitat selection is fundamentally important to animal ecology, and animals that
      can learn about habitats can increase the probability of avoiding detection by
      predators or quickly finding food. Here, we tested whether juveniles of the red
      swamp crayfish, Procambarus clarkii, can learn preference for habitat types based
      on experience with food availability. Crayfish were housed in arenas with two
      habitat types, half leaf habitat and half rock habitat. Over several days,
      crayfish were fed consistently in one of the habitat types. Initial tests
      revealed that crayfish had an innate preference for the leaf habitat, but
      conditioning over 2-3 weeks was sufficient to shift this preference to the rock
      habitat based on habitat cues rather than other spatial cues in their
      environment. The ability to learn the relevance of habitat features may be an
      important trait for the colonization success, and subsequent impact, of
      introduced species.

PMID- 29330087
TI  - Comparing the antipredator behaviour of two sympatric, but not syntopic,
      Liolaemus lizards.
AB  - The microhabitat preferences of prey animals can modulate how they perceive
      predation risk, and therefore, their antipredator behaviour. We tested under
      standardized conditions how microhabitat preferences of two Liolaemus lizards
      affected their responses when confronted with two types of ambush predators
      (raptor vs. snake), under two levels of predation risk (low vs. high). These
      lizard species are sympatric, but not syntopic; L. chiliensis basks on bushes, a
      complex microhabitat that may provide protection against visual predators, while
      L. nitidus prefers open microhabitats, basking on the top of large bare rocks,
      highly exposed to visual predators. If microhabitat complexity modulates the
      antipredator response, L. chiliensis may perceive lower predation risk,
      exhibiting lower intensity of antipredator responses than L. nitidus. Both
      species reduced their activity after being exposed to both predators, but lizards
      differed in the assessment of predation risk; L. nitidus reduced its activity
      independently of the predation risk experienced, while L. chiliensis only reduced
      its activity in the high-risk condition. The microhabitat preferences shaped
      during the evolution of these species seem to modulate their perception of
      predation risk, which may cause interspecific differences in the associated costs
      of their antipredator responses.

PMID- 29330088
TI  - The flight of the locus of selection: Some intricate relationships between
      evolutionary elements.
AB  - Selection has enriched our understanding of the world since it was first applied
      to the evolution of species. Selection stands as an alternative to essentialist
      thinking, as a generalized and multiply applicable concept, and as a causal
      explanation for current forms within biology and behavior. Attempts to describe
      selection processes in a generalizable way have provided clarity about their
      minimal elements, such as replicators and interactors. This paper discusses the
      interconnectedness among different levels of selection using evidence garnered
      from evolutionary biology, development, epigenetics, neuroscience, and behavior
      analysis. Currently, it appears that replicators and interactors may be more
      fluid than previously supposed and that selection for particular traits may rely
      on both multiple levels of interaction and multiple levels of replication.
      Replicators, interactors, and environment share influence on one another, and
      different replicators may exchange critical control over similar interactor
      variation as evolution proceeds. Our current understanding of selection continues
      to undergo revision, and reference to a number of disparate fields can help to
      account for the complexity of these processes. An understanding of their
      interconnectedness may help resolve some mysteries that develop in fields that
      exclusively focus on one or a few, such as the focused study of behavior.

PMID- 29330089
TI  - Grouping promotes risk-taking in unfamiliar settings.
AB  - Acting collectively in a group provides risk-reducing benefits. Yet individuals
      differ in how they take risks, with some being more willing than others to
      approach dangerous or unfamiliar settings. Therefore, individuals may need to
      adjust their behaviour when in groups, either as a result of perceiving greater
      safety or to coordinate collective responses, the latter of which may rely on
      within-group dynamics biased by group composition. In zebrafish we explored how
      these aspects of grouping affect risk-taking behaviour by comparing solitary to
      group conditions and testing the ability of group-member solitary responses to
      predict collective responses. We focused on approach-latency towards a novel
      object and an unusual food to test this, for shoals of five fish. There was no
      indication that collective latencies are predicted by how each fish responded
      when alone in terms of the extremes, the variance or the mean of group-member
      latency towards the unusual food and the novel-object. However, fish were overall
      faster and less variable in their approach when shoaling. This indicates lower
      risk aversion by individuals in groups, presumably as a result of group safety.
      An interesting consequence of the overall low risk-aversion in shoals is that
      more risk-aversive fish adjust their behaviour more than less risk averse fish.

PMID- 29330085
TI  - Inflammation following acute myocardial infarction: Multiple players, dynamic
      roles, and novel therapeutic opportunities.
AB  - Acute myocardial infarction (AMI) and the heart failure that often follows, are
      major causes of death and disability worldwide. As such, new therapies are
      required to limit myocardial infarct (MI) size, prevent adverse left ventricular
      (LV) remodeling, and reduce the onset of heart failure following AMI. The
      inflammatory response to AMI, plays a critical role in determining MI size, and a
      persistent pro-inflammatory reaction can contribute to adverse post-MI LV
      remodeling, making inflammation an important therapeutic target for improving
      outcomes following AMI. In this article, we provide an overview of the multiple
      players (and their dynamic roles) involved in the complex inflammatory response
      to AMI and subsequent LV remodeling, and highlight future opportunities for
      targeting inflammation as a therapeutic strategy for limiting MI size, preventing
      adverse LV remodeling, and reducing heart failure in AMI patients.

PMID- 29330090
TI  - Evaluation of the confusion matrix method in the validation of an automated
      system for measuring feeding behaviour of cattle.
AB  - The aim of the present study was to evaluate empirically confusion matrices in
      device validation. We compared the confusion matrix method to linear regression
      and error indices in the validation of a device measuring feeding behaviour of
      dairy cattle. In addition, we studied how to extract additional information on
      classification errors with confusion probabilities. The data consisted of 12 h
      behaviour measurements from five dairy cows; feeding and other behaviour were
      detected simultaneously with a device and from video recordings. The resulting
      216 000 pairs of classifications were used to construct confusion matrices and
      calculate performance measures. In addition, hourly durations of each behaviour
      were calculated and the accuracy of measurements was evaluated with linear
      regression and error indices. All three validation methods agreed when the
      behaviour was detected very accurately or inaccurately. Otherwise, in the
      intermediate cases, the confusion matrix method and error indices produced
      relatively concordant results, but the linear regression method often disagreed
      with them. Our study supports the use of confusion matrix analysis in validation
      since it is robust to any data distribution and type of relationship, it makes a
      stringent evaluation of validity, and it offers extra information on the type and
      sources of errors.

PMID- 29330091
TI  - CDC42EP4, a perisynaptic scaffold protein in Bergmann glia, is required for
      glutamatergic tripartite synapse configuration.
AB  - Configuration of tripartite synapses, comprising the pre-, post-, and peri
      synaptic components (axon terminal or bouton, dendritic spine, and astroglial
      terminal process), is a critical determinant of neurotransmitter kinetics and
      hence synaptic transmission. However, little is known about molecular basis for
      the regulation of tripartite synapse morphology. Previous studies showed that
      CDC42EP4, an effector protein of a cell morphogenesis regulator CDC42, is
      expressed exclusively in Bergmann glia in the cerebellar cortex, that it forms
      tight complex with the septin heterooligomer, and that it interacts indirectly
      with the glutamate transporter GLAST and MYH10/nonmuscle myosin IotaIotaB.
      Scrutiny of Cdc42ep4-/- mice had revealed that the CDC42EP4-septins-GLAST
      interaction facilitates glutamate clearance, while the role for CDC42EP4-septins
      MYH10 interaction has remained unsolved. Here, we find anomalous configuration of
      the tripartite synapses comprising the parallel fiber boutons, dendritic spines
      of Purkinje cells, and Bergmann glial processes in Cdc42ep4-/- mice. The complex
      anomalies include 1) recession of Bergmann glial membranes from the nearest
      active zones, and 2) extension of nonactive synaptic contact around active zone.
      In line with the recession of Bergmann glial membranes by the loss of CDC42EP4,
      overexpression of CDC42EP4 in heterologous cells promotes cell spreading and
      partitioning of MYH10 to insoluble (i.e., active) fraction. Paradoxically,
      however, Cdc42ep4-/- cerebellum contained significantly more MYH10 and N
      cadherin, which is attributed to secondary neuronal response mainly in Purkinje
      cells. Given cooperative actions of N-cadherin and MYH10 for adhesion between
      neurons, we speculate that their augmentation may reflect the extension of
      nonactive synaptic contacts in Cdc42ep4-/- cerebellum. Transcellular mechanism
      that links the absence of CDC42EP4 in Bergmann glia to the augmentation of N
      cadherin and MYH10 in neurons is currently unknown, but the phenotypic similarity
      to GLAST-null mice indicates involvement of the glutamate intolerance. Together,
      the unique phenotype of Cdc42ep4-/- mice provides a clue to novel molecular
      network underlying tripartite synapse configuration.

PMID- 29330092
TI  - A novel double-antigen sandwich ELISA for the species-independent detection of
      Crimean-Congo hemorrhagic fever virus-specific antibodies.
AB  - Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne disease in humans caused
      by the CCHF virus (CCHFV). The detection of anti-CCHFV antibodies in animals is
      used to reveal infection risk areas. Therefore a simple, quick and reliable
      multispecies assay for the detection of CCHFV-specific antibodies is needed. This
      work presents the development and validation of a novel CCHF double-antigen ELISA
      for the detection of anti-CCHFV nucleoprotein antibodies. The test requires 30
      MUl of serum, and results are obtained within 90 min. As the ELISA is based on
      recombinant N-protein of the IbAr10200 virus, it can be run under standard
      biosafety conditions. For assay validation, sera from 95 cattle and 176 small
      ruminants from CCHF-endemic regions (origin: Albania, Cameroon, Kosovo, Former
      Yugoslav Republic of Macedonia, Mauritania, Pakistan, Turkey) served as a
      positive reference serum panel. The CCHF antibody status of the positive
      reference samples had been previously confirmed by two serological assays
      (species-adapted VectorBest ELISA and Euroimmun IFA). CCHFV strains belonging to
      three different clades are known to circulate in the countries where the positive
      samples originated. Sera from 402 cattle and 804 small ruminants from Germany and
      France served as the negative serum panel, as both countries are considered
      outside of the CCHFV endemic zone. Sera from monkeys, camels, rats, ferrets,
      raccoon dogs, raccoons, foxes, hares, pigs and humans were also tested, to
      determine the suitability of this novel ELISA for these species. All negative
      reference sera were confirmed by the CCHF double-antigen ELISA, indicating a
      specificity of 100%. 268 of 271 positive reference sera tested positive for CCHFV
      specific antibodies, 8sensitivity of 99%9. Further analysis are needed to ensure
      a recognition of the IbAr10200 nucleoprotein by antibodies directed against all
      known CCHFV clades. This is planned to be realized with sera from other regions
      covering the three missing clades.

PMID- 29330094
TI  - P21 activated kinase signaling in cancer.
AB  - The p21 Activated Kinases (PAKs) are a family of serine threonine kinases, that
      consist of 6 members, PAKs 1-6, which are positioned at an intersection of
      multiple signaling pathways implicated in oncogenesis. The PAKs were originally
      identified as protein kinases that function downstream of the Ras related Rho
      GTPases Cdc42 and Rac. PAK1 and PAK4, which belong to Group I and Group II PAKs,
      respectively, are most often associated with tumorigenesis. On account of their
      well characterized roles in cancer, several small molecule inhibitors are being
      developed to inhibit the PAKs, and there is interest in investigating their
      efficacy as either first line or adjuvant treatments for cancer. Studies to
      delineate PAK regulated signaling pathways as well as the long term effects of
      PAK overexpression on gene expression are beginning to shed light on the
      mechanism by which PAK proteins may lead to cancer when they are overexpressed or
      activated. This review will describe the association between PAK expression in
      cancer, with a focus on PAK1 and PAK4, which are most often associated with the
      disease. The current understanding of the molecular mechanisms by which the PAKs
      operate in cancer will be discussed. We will also review some of the potential
      drug candidates, and discuss which of them are currently being tested for their
      efficacy in cancer treatments.

PMID- 29330093
TI  - Designing improved active peptides for therapeutic approaches against infectious
      diseases.
AB  - Infectious diseases are one of the main causes of human morbidity and mortality.
      In the last few decades, pathogenic microorganisms' resistance to conventional
      drugs has been increasing, and it is now pinpointed as a major worldwide health
      concern. The need to search for new therapeutic options, as well as improved
      treatment outcomes, has therefore increased significantly, with biologically
      active peptides representing a new alternative. A substantial research effort is
      being dedicated towards their development, especially due to improved
      biocompatibility and target selectivity. However, the inherent limitations of
      peptide drugs are restricting their application. In this review, we summarize the
      current status of peptide drug development, focusing on antiviral and
      antimicrobial peptide activities, highlighting the design improvements needed,
      and those already being used, to overcome the drawbacks of the therapeutic
      application of biologically active peptides.

PMID- 29330095
TI  - Crosstalk between Rac1-mediated actin regulation and ROS production.
AB  - The small RhoGTPase Rac1 is implicated in a variety of events related to actin
      cytoskeleton rearrangement. Remarkably, another event that is completely
      different from those related to actin regulation has the same relevance; the Rac1
      mediated production of reactive oxygen species (ROS) through NADPH oxidases
      (NOX). Each outcome involves different Rac1 downstream effectors; on one hand,
      events related to the actin cytoskeleton require Rac1 to bind to WAVEs proteins
      and PAKs that ultimately promote actin branching and turnover, on the other, NOX
      derived ROS production demands active Rac1 to be bound to a cytosolic activator
      of NOX. How Rac1-mediated signaling ends up promoting actin-related events, NOX
      derived ROS, or both is poorly understood. Rac1 regulators, including scaffold
      proteins, are known to exert tight control over its functions. Hence, evidence of
      Rac1 regulatory events leading to both actin remodeling and NOX-mediated ROS
      generation are discussed. Moreover, cellular functions linked to physiological
      and pathological conditions that exhibit crosstalk between Rac1 outcomes are
      analyzed, while plausible roles in neuronal functions (and dysfunctions) are
      highlighted. Together, discussed evidence shed light on cellular mechanisms which
      requires Rac1 to direct either actin- and/or ROS-related events, helping to
      understand crucial roles of Rac1 dual functionality.

PMID- 29330096
TI  - Selenoprotein H controls cell cycle progression and proliferation of human
      colorectal cancer cells.
AB  - Selenoprotein H (SELENOH) is supposed to be involved in redox regulation as well
      as in tumorigenesis. However, its role in healthy and transformed cells of the
      gastrointestinal tract remains elusive. We analyzed SELENOH expression in cells
      depending on their selenium supply and differentiation status and found that
      SELENOH expression was increased in tumor tissue, in undifferentiated epithelial
      cells from mice and in colorectal cancer lines as compared to more differentiated
      ones. Knockdown studies in human colorectal cancer cells revealed that repression
      of SELENOH decreased cellular differentiation and increased proliferation and
      migration. In addition, SELENOH knockdown cells have a higher competence to form
      colonies or tumor xenografts. In parallel, they show a faster cell cycle
      transition. The high levels of SELENOH in tumors as well as in undifferentiated,
      proliferative cells together with its inhibitory effects on proliferation and
      G1/S phase transition suggest SELENOH as a key regulator for cell cycle
      progression and for prevention of uncontrolled proliferation. As SELENOH
      expression is highly dependent on the selenium status, effects of selenium
      supplementation on cancer initiation and progression appear to involve SELENOH.

PMID- 29330098
TI  - Missed Opportunities in Colorectal Cancer Prevention in Patients With Inadequate
      Bowel Preparations.

PMID- 29330099
TI  - Confusion for Fifteen Years: A Case of Abernethy Malformation.

PMID- 29330097
TI  - Learning situated emotions.
AB  - From the perspective of constructivist theories, emotion results from learning
      assemblies of relevant perceptual, cognitive, interoceptive, and motor processes
      in specific situations. Across emotional experiences over time, learned
      assemblies of processes accumulate in memory that later underlie emotional
      experiences in similar situations. A neuroimaging experiment guided participants
      to experience (and thus learn) situated forms of emotion, and then assessed
      whether participants tended to experience situated forms of the emotion later.
      During the initial learning phase, some participants immersed themselves in
      vividly imagined fear and anger experiences involving physical harm, whereas
      other participants immersed themselves in vividly imagined fear and anger
      experiences involving negative social evaluation. In the subsequent testing
      phase, both learning groups experienced fear and anger while their neural
      activity was assessed with functional magnetic resonance imaging (fMRI). A
      variety of results indicated that the physical and social learning groups
      incidentally learned different situated forms of a given emotion. Consistent with
      constructivist theories, these findings suggest that learning plays a central
      role in emotion, with emotion adapted to the situations in which it is
      experienced.

PMID- 29330100
TI  - Osteoarthritis year in review 2017: updates on imaging advancements.
AB  - OBJECTIVE: This narrative review covers original research publications related to
      imaging advancements in osteoarthritis (OA) published in the English language
      between 1st April 2016 and 30th April 2017. METHODS: Relevant human studies
      (excluding pre-clinical and in vitro studies), were searched and selected from
      PubMed database using the search terms of "osteoarthritis (OA)" in combination
      with "radiography", "magnetic resonance imaging (MRI)", "computed tomography
      (CT)", "ultrasound", "positron emission tomography (PET)," "single-photon
      emission computed tomography (SPECT)," and "scintigraphy". The included studies
      were sorted according to their relevance, novelty, and impact. Original research
      articles with both imaging advancements and novel clinical information were
      discussed in this review. RESULTS: A large portion of the published studies were
      focused on MRI-based semi-quantitative and quantitative (morphological and
      structural) metrics of the knee joint to assess OA-related structural damages.
      New imaging technologies, such as PET, have been investigated for OA diagnosis
      and characterization, the delineation of predictive factors for OA progression,
      and to monitor the treatment responses. CONCLUSION: Advanced imaging modalities
      play a pivotal role in OA research, and make a significant contribution to our
      understanding of OA diagnosis, pathogenesis, risk stratification, and prognosis.

PMID- 29330101
TI  - Telephone-based weight loss support for patients with knee osteoarthritis: a
      pragmatic randomised controlled trial.
AB  - OBJECTIVE: To determine the effectiveness of telephone-based weight loss support
      in reducing the intensity of knee pain in patients with knee osteoarthritis, who
      are overweight or obese, compared to usual care. DESIGN: We conducted a parallel
      randomised controlled trial (RCT), embedded within a cohort multiple RCT of
      patients on a waiting list for outpatient orthopaedic consultation at a tertiary
      referral hospital in NSW, Australia. Patients with knee osteoarthritis,
      classified as overweight or obese [body mass index (BMI) between >=27 kg/m2 and
      <40 kg/m2] were randomly allocated to receive referral to an existing non-disease
      specific government funded 6-month telephone-based weight management and healthy
      lifestyle service or usual care. The primary outcome was knee pain intensity
      measured using an 11-point numerical rating scale (NRS) over 6-month follow-up. A
      number of secondary outcomes, including self-reported weight were measured. Data
      analysis was by intention-to-treat according to a pre-published analysis plan.
      RESULTS: Between May 19 and June 30 2015, 120 patients were randomly assigned to
      the intervention (59 analysed, one post-randomisation exclusion) or usual care
      (60 analysed). We found no statistically significant between group differences in
      pain intensity [area under the curve (AUC), mean difference 5.4, 95%CI: -13.7 to
      24.5, P = 0.58] or weight change at 6 months (self-reported; mean difference 
      0.4, 95%CI: -2.6 to 1.8, P = 0.74). CONCLUSIONS: Among patients with knee
      osteoarthritis who are overweight, telephone-based weight loss support, provided
      using an existing 6-month weight management and healthy lifestyle service did not
      reduce knee pain intensity or weight, compared with usual care. TRIAL
      REGISTRATION NUMBER: ACTRN12615000490572.

PMID- 29330102
TI  - Bisphosphonates intake and its association with changes of periarticular bone
      area and three-dimensional shape: data from the Osteoarthritis Initiative (OAI).
AB  - OBJECTIVE: To determine the association between bisphosphonate treatment with the
      change of periarticular bone area and three-dimensional (3D) shape in
      participants of the Osteoarthritis Initiative (OAI) study. DESIGN: Using
      propensity score (PS) matching method in females, 48 bisphosphonate users and 105
      non-users, who were matched for osteoarthritis (OA) and osteoporosis (OP) related
      factors were included. Baseline and 24-month magnetic resonance imaging (MRI)
      based periarticular bone area and 3D shape measurements were used. The
      association between bisphosphonate intake and 24-month interval changes of the
      periarticular bone area and 3D shape were evaluated using paired Wilcoxon signed
      rank test. We used conditional logistic regression models for determining the
      association between bisphosphonate intake and periarticular bone change, defined
      using the standard deviation of difference (SDD) and reliable change index (RCI)
      methods. P-values have been adjusted for multiple comparisons using Benjamini &
      Hochberg procedure and false discovery rate (FDR)-adjusted P-values were
      reported. RESULTS: The 24-month interval increases in the periarticular bone area
      in medial side of tibia were significantly greater in non-users than users (FDR
      adjusted P-value: 0.002). There was an approaching significance trend for lower
      medial tibial periarticular bone area expansion in bisphosphonate users in
      comparison with non-users (For 1SDD change, odds ratio 95% confidence interval
      (OR (95% CI)): 0.514 (0.271-0.975), FDR-adjusted P-value: 0.085) (For 1.96RCI
      change, OR (95% CI): 0.552 (0.309-0.986), FDR-adjusted P-value: 0.085).
      CONCLUSIONS: Bisphosphonate intake was associated with a reduction in the odds
      (approaching but not achieving significance) of expansion periarticular bone
      area, specifically in the medial tibial sub-region.

PMID- 29330103
TI  - Osteoarthritis year in review 2017: rehabilitation and outcomes.
AB  - OBJECTIVE: The purpose of this systematic review was to describe studies
      examining rehabilitation for people with osteoarthritis (OA) and to summarize
      findings from selected key systematic reviews (SRs) and randomized controlled
      trials (RCTs). DESIGN: A systematic search was performed using Pubmed, Embase and
      Cochrane databases from April 1st 2016 to May 15th 2017 using the terms
      'osteoarthritis', 'randomized controlled trial', and 'systematic review'.
      Inclusion criteria were: clinically or radiologically diagnosed patients with OA,
      rehabilitation treatment, RCT or SRs. A selection of the included studies is
      discussed based on study quality and perceived importance to the field; including
      those that are innovative, inform the direction of the field or generate
      controversy. Methodological quality of the included studies was assessed using
      the PEDro-scale for RCTs and the Amstar guideline for SRs. RESULTS: From 1211
      articles, 80 articles met the eligibility criteria including 21 SRs and 61 RCTs.
      The median of the methodological quality of the SRs and RCTs was 7 (2-9) and 6 (3
      10), respectively. The studies were grouped into several themes, covering the
      most important rehabilitation fields. CONCLUSIONS: Striking is the small number
      of studies investigating another joint (18%) than the knee (82%). Exercise is the
      most common treatment evaluated and should be accompanied with education to
      effectuate a behavioural change in physical activity of people with OA. No new
      insights in the field of braces (or orthoses) and in the field of acupuncture
      were found.

PMID- 29330104
TI  - Circular RNA: An emerging non-coding RNA as a regulator and biomarker in cancer.
AB  - Circular RNA (circRNA) is a type of covalently closed non-coding RNA that may
      regulate gene expression in eukaryotes. The recent application of high-throughput
      RNA sequencing and bioinformatics approaches has revealed a large number of
      circRNAs in human cells. Emerging evidence indicates that many circRNAs have cell
      type specific expression and are linked to physiological development and various
      diseases. Specially, circRNAs can either serve as oncogenic stimuli or tumor
      suppressors in cancer. circRNAs have also been shown to be enriched and stable in
      extracellular fluid, indicating the potential of circRNAs as cancer biomarkers.
      Here, we summarize the current knowledge of circRNAs, including their
      classification, biogenesis, properties, and databases, as well as their function
      and clinical implications in cancer.

PMID- 29330105
TI  - Redox regulation of microRNAs in cancer.
AB  - Dysregulation of microRNAs (miRNAs) has long been implicated in tumorigenesis,
      whereas the underlying mechanisms remain largely unknown. Oxidative stress is a
      hallmark of cancer that involved in multiple pathophysiological processes,
      including the aberrant regulation of miRNAs. Compelling evidences have implied
      complicated interplay between reactive oxygen species (ROS) and miRNAs. Indeed,
      ROS induces carcinogenesis through either reducing or increasing the miRNA level,
      leading to the activation of oncogenes or silence of tumor suppressors,
      respectively. In turn, miRNAs target ROS productive genes or antioxidant
      responsive elements to affect cellular redox balance, which contributes to
      establishing a microenvironment favoring cancer cell growth and metastasis. Both
      miRNAs and ROS have been identified as potential biomarkers and therapeutic
      targets in human malignancies, and comprehensive understanding of the molecular
      events herein will facilitate the development of novel cancer therapeutic
      strategies.

PMID- 29330106
TI  - Featuring the special issue Guest Editor.

PMID- 29330107
TI  - Prostate cancer-associated lncRNAs.
AB  - Long non-coding RNA (LncRNA) is defined as an RNA transcript that does not encode
      any protein, with a length longer than 200 nt. Based on the recent advances in
      high-throughput sequencing techniques, a large number of lncRNAs have been
      characterized as functional transcripts that play important roles in various
      biological processes as well as pathologic states. In a research field of
      prostate cancer, several key lncRNAs have been identified as new players that
      contribute to the pathophysiology of the disease, which is primarily regulated by
      androgen and its cognate receptor. This review sheds light on the history and
      future perspective of these prostate cancer-associated lncRNAs.

PMID- 29330108
TI  - Membrane-lipid associated lncRNA: A new regulator in cancer signaling.
AB  - Long noncoding RNAs (LncRNAs) are one of the emerging regulators which are
      involved in diverse biological processes. LncRNAs can participate in the
      regulation of gene expression via various ways in the cytoplasm and the nucleus.
      The function of the nuclear lncRNAs has been studied a lot. Recent studies have
      shown that the regulatory roles of cytoplasmic lncRNA, including membrane lipid
      associated lncRNA, which may open an unexplored mechanistic territory. LncRNA
      dysregulated expression represents a common event in pathogenesis of a variety of
      human genetic diseases including cancer. Lipid-associated lncRNA is capable of
      modulating critical cellular functions by directly interacting with phospholipids
      on the plasma membrane. Besides, it also could be a predictor for the poor
      prognosis of cancer. In this review, we sum up the roles of cytoplasmic lncRNA,
      especially lipid-associated lncRNA in cancer.

PMID- 29330109
TI  - Friend or Foe: MicroRNAs in the p53 network.
AB  - The critical tumor suppressor gene TP53 is either lost or mutated in more than
      half of human cancers. As an important transcriptional regulator, p53 modulates
      the expression of many microRNAs. While wild-type p53 uses microRNAs to suppress
      cancer development, microRNAs that are activated by gain-of-function mutant p53
      confer oncogenic properties. On the other hand, the expression of p53 is tightly
      controlled by a fine-tune machinery including microRNAs. MicroRNAs can target the
      TP53 gene directly or other factors in the p53 network so that expression and
      function of either the wild-type or the mutant forms of p53 is downregulated.
      Therefore, depending on the wild-type or mutant p53 context, microRNAs contribute
      substantially to suppress or exacerbate tumor development.

PMID- 29330110
TI  - Epigenetics and pathogenesis of systemic sclerosis; the ins and outs.
AB  - The pathogenesis of many diseases is influenced by environmental factors which
      can affect human genome and be inherited from generation to generation. Adverse
      environmental stimuli are recognized through the epigenetic regulatory complex,
      leading to gene expression alteration, which in turn culminates in disease
      outcomes. Three epigenetic regulatory mechanisms modulate the manifestation of a
      gene, namely DNA methylation, histone changes, and microRNAs. Both epigenetics
      and genetics have been implicated in the pathogenesis of systemic sclerosis (SSc)
      disease. Genetic inheritance rate of SSc is low and the concordance rate in both
      monozygotic (MZ) and dizygotic (DZ) twins is little, implying other possible
      pathways in SSc pathogenesis scenario. Here, we provide an extensive overview of
      the studies regarding different epigenetic events which may offer insights into
      the pathology of SSc. Furthermore, epigenetic-based interventions to treat SSc
      patients were discussed.

PMID- 29330111
TI  - Soluble Major Histocompatibility Complex Class I related Chain A (sMICA) levels
      influence graft outcome following Renal Transplantation.
AB  - BACKGROUND: Since soluble isoforms of MICA play an important role in modulating
      the immune response, we evaluated a possible correlation between their levels and
      development of acute rejection following renal transplantation. METHODS: Serum
      samples collected at pre- and different time points post-transplant from 137 live
      related donor renal transplant recipients were evaluated retrospectively for
      sMICA levels and for the presence of MICA antibodies. Samples from 30 healthy
      volunteers were also tested as controls. RESULTS: Significantly higher levels of
      sMICA were observed in the pretransplant sera of allograft recipients as compared
      to healthy controls. Patients with acute cellular rejection experienced a
      significant fall in their levels at the time of diagnosis as compared to their
      pretransplant values and posttransplant follow up time points (p = .01, .003,
      .005 and .04 respectively at pre vs biopsy (Bx), POD7 vs Bx, POD 30 vs Bx, POD 90
      vs Bx). However, no such difference was noted in patients undergoing antibody
      mediated rejection. Further the study did not reveal any correlation on the
      presence/absence of MICA antibodies with either an increase or decrease in sMICA
      levels. CONCLUSIONS: Estimating circulating levels of soluble MICA could provide
      useful information of prognostic importance in assessing graft outcome following
      renal transplantation.

PMID- 29330113
TI  - Runt-related transcription factor 1 (RUNX1) deficiency attenuates inflammation
      induced pro-inflammatory and pro-labour mediators in myometrium.
AB  - Identifying new targets that regulate myometrial activation are required to
      develop effective treatments to stop preterm labor. Inflammation, which can be
      induced by sterile or infective insults, plays a role in initiating and
      maintaining uterine contractions. Several high throughput transcription screening
      studies have identified an upregulation of runt-related transcription factor 1
      (RUNX1) mRNA expression in myometrium with labor. The role of RUNX1 in labor,
      however, is not known. We report increased RUNX1 during late gestation which was
      further augmented in labor, suggesting that RUNX1 may be involved in the
      transition of the myometrium from a quiescent into a contractile state in
      preparation for labor. By inhibiting the expression of RUNX1, we have established
      that RUNX1 induces the expression of pro-inflammatory cytokines, chemokines,
      adhesion molecules, contraction-associated proteins OXR and PTGFR, the uterotonic
      PGF2alpha, and the ECM remodelling enzyme MMP9. Targeting RUNX1 may be a novel
      approach to prevent preterm labor.

PMID- 29330112
TI  - Macrochimerism and clinical transplant tolerance.
AB  - Current theory holds that macrochimerism is essential to the development of
      transplant tolerance. Hematopoietic cell transplantation from the solid organ
      donor is necessary to achieve macrochimerism. Over the last 10-20 years, trials
      of tolerance induction with combined kidney and hematopoietic cell
      transplantation have moved from the preclinical to the clinical arena. The
      achievement of macrochimerism in the clinical setting is challenging, and
      potentially toxic due to the conditioning regimen necessary to hematopoietic cell
      transplantation and due to the risk of graft-versus-host disease. There are
      differences in chimerism goals and methods of the three major clinical stage
      tolerance induction strategies in both HLA-matched and HLA-mismatched living
      donor kidney transplantation, with consequent differences in efficacy and safety.
      The Stanford protocol has proven efficacious in the induction of tolerance in HLA
      matched kidney transplantation, allowing cessation of immunosuppressive drug
      therapy in 80% of study participants, with the safety profile of conventional
      transplantation. In HLA-mismatched transplantation, multi-lineage macrochimerism
      of over a year's duration can now be consistently achieved with the Stanford
      protocol, with complete withdrawal of immunosuppressive drug therapy during the
      second post-transplant year as the next experimental step and test of tolerance.

PMID- 29330114
TI  - Human CD4+ CD25+ CD127hi cells and the Th1/Th2 phenotype.
AB  - CD4+ T cells that co-express CD25 and CD127 (CD25+CD127+) make up around 20% of
      all circulating CD4+ memory T cells in healthy people. The clinical significance
      of these cells is that in children with type 1 diabetes their relative frequency
      at diagnosis is significantly and directly correlated with rate of disease
      progression. The purpose of this study was to further characterize the
      CD25+CD127hi cells. We show that they are a mix of Th1 and Th2 cells however,
      they have a significantly higher relative frequency of pre-committed and
      committed Th2 cells, and secrete significantly higher levels of Th2-type
      cytokines than CD25- memory T cells. Further, these cells are neither exhausted
      nor senescent and proliferate to the same extent as CD25- memory cells. Thus,
      CD25+CD127hi cells are a highly active subset of memory T cells that might play a
      role in controlling inflammation via anti-inflammatory Th2-type deviation.

PMID- 29330115
TI  - Pediatric-onset Evans syndrome: Heterogeneous presentation and high frequency of
      monogenic disorders including LRBA and CTLA4 mutations.
AB  - Evans syndrome (ES) is defined by the combination of autoimmune hemolytic anemia
      and immune thrombocytopenia. Clinical presentation includes manifestations of
      immune dysregulation, found in primary immune deficiencies, autoimmune
      lymphoproliferative syndrome with FAS (ALPS-FAS), Cytotoxic T Lymphocyte Antigen
      4 (CTLA-4) and Lipopolysaccharide-Responsive vesicle trafficking Beige-like and
      Anchor protein (LRBA) defects. We report the clinical history and genetic results
      of 18 children with ES after excluding ALPS-FAS. Thirteen had organomegaly, five
      lymphocytic infiltration of non-lymphoid organs, nine hypogammaglobulinemia and
      fifteen anomalies in lymphocyte phenotyping. Seven patients had genetic defects:
      three CTLA4 mutations (c.151C>T; c.109+1092_568-512del; c.110-2A>G) identified by
      Sanger sequencing and four revealed by Next Generation Sequencing: LRBA
      (c.2450+1C>T), STAT3 gain-of-function (c.2147C>T; c.2144C>T) and KRAS (c.37G>T).
      No feature emerged to distinguish patients with or without genetic diagnosis. Our
      data on pediatric-onset ES should prompt physicians to perform extensive
      screening for mutations in the growing pool of genes involved in primary immune
      deficiencies with autoimmunity.

PMID- 29330116
TI  - TNF-alpha increases Staphylococcus aureus-induced death of human alveolar
      epithelial cell line A549 associated with RIP3-mediated necroptosis.
AB  - AIM: To explore the role of tumor necrosis factor-alpha (TNF-alpha) on
      Staphylococcus aureus-induced necroptosis in alveolar epithelial cells. MAIN
      METHODS: The A549 alveolar epithelial cell line was pretreated with small
      interfering RNA (siRNA) against receptor interacting protein-3 (RIP3) and then
      stimulated by S. aureus, where some cells were pretreated with TNF-alpha or TNF
      alpha with anti-TNF-alpha antibody simultaneously. A549 cell death was assessed
      using lactate dehydrogenase (LDH) leakage and flow cytometry analyses. The
      protein expressions of RIP1, RIP3, cleaved caspase-1, and cleaved caspase-8 were
      analyzed by western blot. KEY FINDINGS: S. aureus-induced LDH release was
      increased significantly by TNF-alpha. In addition, flow cytometry showed that TNF
      alpha increased A549 cell apoptosis and necrosis in S. aureus-infected cell
      cultures. Levels of RIP3 and cleaved caspase-1 protein in A549 cells infected
      with S. aureus increased at 12 h post-infection, as shown by western blot.
      Significant additional increases in RIP3 expression were observed following the
      addition of TNF-alpha. Decreasing RIP3 levels by siRNA significantly suppressed
      the release of LDH induced by TNF-alpha and S. aureus. RIP3 siRNA also
      significantly suppressed A549 cell necrosis induced by S. aureus and TNF-alpha at
      6 and 12 h post-infection as shown by flow cytometry analysis. SIGNIFICANCE: TNF
      alpha enhances the damage of S. aureus on lung epithelial cells, and its
      mechanism is associated with RIP3 mediated necroptosis.

PMID- 29330118
TI  - Using the Ribodeblur pipeline to recover A-sites from yeast ribosome profiling
      data.
AB  - Ribosome profiling has emerged as a powerful technique to study mRNA translation.
      Ribosome profiling has the potential to determine the relative quantities and
      locations of ribosomes on mRNA genome wide. Taking full advantage of this
      approach requires accurate measurement of ribosome locations. However,
      experimental inconsistencies often obscure the positional information encoded in
      ribosome profiling data. Here, we describe the Ribodeblur pipeline, a
      computational analysis tool that uses a maximum likelihood framework to infer
      ribosome positions from heterogeneous datasets. Ribodeblur is simple to install,
      and can be run on an average modern Mac or Linux-based laptop. We detail the
      process of applying the pipeline to high-coverage ribosome profiling data in
      yeast, and discuss important considerations for potential extension to other
      organisms.

PMID- 29330117
TI  - RIFM fragrance ingredient safety assessment phenethyl isovalerate, CAS Registry
      Number 140-26-1.

PMID- 29330119
TI  - Temporal changes of the bacterial community colonizing wheat straw in the cow
      rumen.
AB  - This study used Miseq pyrosequencing and scanning electron microscopy to
      investigate the temporal changes in the bacterial community tightly attached to
      wheat straw in the cow rumen. The wheat straw was incubated in the rumens and
      samples were recovered at various times. The wheat straw degradation exhibited
      three phases: the first degradation phase occurred within 0.5 h, and the second
      degradation phase occurred after 6 h, with a stalling phase occurring between 0.5
      and 6 h. Scanning electron microscopy revealed the colonization of the
      microorganisms on the wheat straw over time. The bacterial communities at 0.5, 6,
      24, and 72 h were determined, corresponding to the degradation phases. Firmicutes
      and Bacteroidetes were the two most dominant phyla in the bacterial communities
      at the four time points. Principal coordinate analysis (PCoA) showed that the
      bacterial communities at the four time points were distinct from each other. The
      wheat straw-associated bacteria stabilized at the phylum level after 0.5 h of
      rumen incubation, and only modest phylum-level and family-level changes were
      observed for most taxa between 0.5 h and 72 h. The relative abundance of the
      dominant genera, Butyrivibrio, Coprococcus, Ruminococcus, Succiniclasticum,
      Clostridium, Prevotella, YRC22, CF231, and Treponema, changed significantly over
      time (P < .05). However, at the genus level, unclassified taxa accounted for
      70.3% +/- 6.1% of the relative abundance, indicating their probable importance in
      the degradation of wheat straw as well as in the temporal changes of the
      bacterial community. Thus, understanding the function of these unclassified taxa
      is of great importance for targeted improvement of forage use efficiency in
      ruminants. Collectively, our results revealed distinct degradation phases of
      wheat straw and corresponding changes in the colonized bacterial community.

PMID- 29330120
TI  - An update on the role of nanovehicles in nose-to-brain drug delivery.
AB  - A quantitative analysis has cast doubt over the limited advantages provided by
      particles for nose-to-brain (NTB) drug delivery. Thus, it is imperative to
      identify the role of nanovehicles in NTB drug delivery. If nanocarriers are used
      merely as an option to improve various properties of the drugs or the
      formulations, it is difficult for them to outperform conventional formulations,
      such as solutions or gels. However, nanovehicles bring about special features,
      such as maintenance of the solubilized state of drugs, sustained or delayed
      release, and enhanced penetration because of surface modifications, all of which
      lead to enhanced NTB delivery efficiency.

PMID- 29330121
TI  - Using network-based expert engagement to advance pharmaceutical research and
      development.

PMID- 29330122
TI  - Privileged portal metastasis of hepatocellular carcinoma in light of the
      coevolution of a visceral portal system and liver in the chordate lineage: a
      search for therapeutic targets.
AB  - Hepatocellular carcinoma (HCC) disseminates systemically, but metastases occur in
      distant organs only in minority of patients, whereas HCC routinely metastasizes
      to liver and its vessels. HCC cells disseminate via hepatic veins, but portal
      veins are affected by metastasis more frequently than are hepatic veins, and
      correlates with poor prognosis. In this review, I suggest that privileged HCC
      portal metastasis occurs because of high levels of pancreatic family hormones and
      growth factors (PHGFs) in the portal blood. The analysis suggests that the
      appearance of the portal system carrying PHGFs in the evolution of invertebrate
      chordate (Amphioxus) led to the evolution of the liver in vertebrate; given that
      the portal pattern of HCC metastasis and selection of more-aggressive clones are
      PHGF dependent, PHGFs and their ligands constitute therapeutic targets.

PMID- 29330124
TI  - Manipulating the epigenome for the treatment of disorders with thrombotic
      complications.
AB  - The haemostatic system is tightly regulated to maintain homeostasis to avoid
      unwanted bleeding or thrombotic complications. Recent research has highlighted
      the importance of epigenetic changes, such as DNA methylation, histone
      modifications, and miRNA-based mechanisms, that alter gene expression. This can
      give rise to dysregulated haemostatic or vascular expressed molecules
      contributing to the development of thrombotic complications. Targeting these
      epigenetic changes could provide a new avenue for the treatment of pathological
      blood clots. However, the lack of tissue specificity warrants high-resolution
      genomic studies of the transcriptome and methylome that will reveal explicit
      epigenetic targets for the design of superior drugs with minimum off-target
      effects.

PMID- 29330125
TI  - The hitchhiker's guide to the chemical-biological galaxy.
AB  - We are used to considering chemical and biological spaces as two different
      entities; although they represent a more-interconnected world, in fact they
      represent a Yin-Yang concept in drug discovery. Chemical-biological space is as
      vast as the universe and, as Douglas Adams famously said, 'Space is big. You just
      won't believe how vastly, hugely, mind-bogglingly big it is'. However, many
      researchers are convinced that it is not so infinite, and are designing
      computational and experimental tools to help identify and explore all possible
      chemical-biological space. Here, we provide an analysis of their approaches and
      discuss possible future research studies.

PMID- 29330123
TI  - A bibliometric review of drug repurposing.
AB  - We have conducted a bibliometric review of drug repurposing by scanning >25
      million papers in PubMed and using text-mining methods to gather, count and
      analyze chemical-disease therapeutic relationships. We find that >60% of the
      ~35,000 drugs or drug candidates identified in our study have been tried in more
      than one disease, including 189 drugs that have been tried in >300 diseases each.
      Whereas in the majority of cases these drugs were applied in therapeutic areas
      close to their original use, there have been striking, and perhaps instructive,
      successful attempts of drug repurposing for unexpected, novel therapeutic areas.

PMID- 29330126
TI  - Recent progress in the discovery of myeloid differentiation 2 (MD2) modulators
      for inflammatory diseases.
AB  - Myeloid differentiation protein 2 (MD2), together with Toll-like receptor 4
      (TLR4), binds lipopolysaccharide (LPS) with high affinity, inducing the formation
      of the activated homodimer LPS-MD2-TLR4. MD2 directly recognizes the Lipid A
      domain of LPS, leading to the activation of downstream signaling of cytokine and
      chemokine production, and initiation of inflammatory and immune responses.
      However, excessive activation and potent host responses generate severe
      inflammatory syndromes such as acute sepsis and septic shock. MD2 is increasingly
      being considered as an attractive pharmacological target for the development of
      potent anti-inflammatory agents. In this Keynote review, we provide a
      comprehensive overview of the recent advances in the structure and biology of
      MD2, and present MD2 modulators as promising agents for anti-inflammatory
      intervention.

PMID- 29330127
TI  - Present drug-likeness filters in medicinal chemistry during the hit and lead
      optimization process: how far can they be simplified?
AB  - During the past decade, decreasing the attrition rate of drug development
      candidates reaching the market has become one of the major challenges in
      pharmaceutical research and drug development (R&D). To facilitate the decision
      making process, and to increase the probability of rapidly finding and developing
      high-quality compounds, a variety of multiparametric guidelines, also known as
      rules and ligand efficiency (LE) metrics, have been developed. However, what are
      the 'best' descriptors and how far can we simplify these drug-likeness prediction
      tools in terms of the numerous, complex properties that they relate to?

PMID- 29330128
TI  - Exploiting ion channel structure to assess rare variant pathogenicity.
AB  - BACKGROUND: A 27-year-old woman was seen for long QT syndrome. She was found to
      be a carrier of 2 variants, KCNQ1 Val162Met and KCNH2 Ser55Leu, and both were
      classified as "pathogenic" by a diagnostic laboratory, in part because of
      sequence proximity to other known pathogenic variants. OBJECTIVE: The purpose of
      this study was to assess the relationship between both the KCNQ1 and KCNH2
      variants and clinical significance using protein structure, in vitro functional
      assays, and familial segregation. METHODS: We used co-segregation analysis of
      family, patch clamp in vitro electrophysiology, and structural analysis using
      recently released cryo-electron microscopy structures of both channels. RESULTS:
      The structural analysis indicates that KCNQ1 Val162Met is oriented away from
      functionally important regions while Ser55Leu is positioned at domains critical
      for KCNH2 fast inactivation. Clinical phenotyping and electrophysiology study
      further support the conclusion that KCNH2 Ser55Leu is correctly classified as
      pathogenic but KCNQ1 Val162Met is benign. CONCLUSION: Proximity in sequence space
      does not always translate accurately to proximity in 3-dimensional space.
      Emerging structural methods will add value to pathogenicity prediction.

PMID- 29330129
TI  - Estradiol up-regulates L-type Ca2+ channels via membrane-bound estrogen
      receptor/phosphoinositide-3-kinase/Akt/cAMP response element-binding protein
      signaling pathway.
AB  - BACKGROUND: In long QT syndrome type 2, women are more prone than men to the
      lethal arrhythmia torsades de pointes. We previously reported that 17beta
      estradiol (E2) up-regulates L-type Ca2+ channels and current (ICa,L) (~30%) in
      rabbit ventricular myocytes by a classic genomic mechanism mediated by estrogen
      receptor-alpha (ERalpha). In long QT syndrome type 2 (IKr blockade or
      bradycardia), the higher Ca2+ influx via ICa,L causes Ca2+ overload, spontaneous
      sarcoplasmic reticulum Ca2+ release, and reactivation of ICa,L that triggers
      early afterdepolarizations and torsades de pointes. OBJECTIVE: The purpose of
      this study was to investigate the molecular mechanisms whereby E2 up-regulates
      ICa,L, which are poorly understood. METHODS: H9C2 and rat myocytes were incubated
      with E2 +/- ER antagonist, or inhibitors of downstream transcription factors, for
      24 hours, followed by western blots of Cav1.2alpha1C and voltage-clamp
      measurements of ICa,L. RESULTS: Incubation of H9C2 cells with E2 (10-100 nM)
      increased ICa,L density and Cav1.2alpha1C expression, which were suppressed by
      the ER antagonist ICI182,780 (1 MUM). Enhanced ICa,L and Cav1.2alpha1C expression
      by E2 was suppressed by inhibitors of phosphoinositide-3-kinase (Pi3K) (30 MUM
      LY294002; P <.05) and Akt (5 MUM MK2206) but not of mitogen-activated protein
      kinase (5 MUM U0126) or protein kinase A (1 MUM KT5720). E2 incubation increased
      p-CREB via the Pi3K/Akt pathway, reached a peak in 20 minutes (3-fold), and
      leveled off to 1.5-fold 24 hours later. Furthermore, a CREB decoy oligonucleotide
      inhibited E2-induced Cav1.2alpha1C expression, whereas membrane-impermeable E2
      (E2-bovine serum albumin) was equally effective at Cav1.2alpha1C up-regulation as
      E2. CONCLUSION: Estradiol up-regulates Cav1.2alpha1C and ICa,L via plasma
      membrane ER and by activating Pi3K, Akt, and CREB signaling. The promoter regions
      of the CACNA1C gene (human-rabbit-rat) contain adjacent/overlapping binding sites
      for p-CREB and ERalpha, which suggests a synergistic regulation by these
      pathways.

PMID- 29330130
TI  - Perioperative electrophysiology study in patients with tetralogy of Fallot
      undergoing pulmonary valve replacement will identify those at high risk of
      subsequent ventricular tachycardia.
AB  - BACKGROUND: Ventricular tachyarrhythmias are the most common cause of death in
      patients with repaired tetralogy of Fallot (TOF), but predicting those at risk
      remains a challenge. An electrophysiology study (EPS) has been proposed to risk
      stratify patients with TOF. OBJECTIVE: We sought to evaluate a perioperative EPS
      guided approach to risk stratify patients with TOF undergoing pulmonary valve
      replacement (PVR) and guide concomitant cryoablation. METHODS: A prospective
      cohort study of patients with TOF undergoing an EPS at the time of PVR from 2006
      to 2017 was conducted at 2 centers. Patients inducible at the time of pre-PVR had
      undergone concomitant cryoablation in addition to PVR. A repeat post-PVR EPS was
      performed in those initially inducible to guide implantable cardioverter
      defibrillator (ICD) implantation. RESULTS: Of 70 patients who underwent a pre-PVR
      EPS, 34 (49%) had inducible sustained ventricular tachycardia (VT): 25
      monomorphic VT and 9 polymorphic VT. Among patients undergoing cryoablation, 14
      (45%) had inducible VT and underwent ICD implantation. During a mean follow-up
      period of 6.1 +/- 3.2 years, 3 patients (21%) had appropriate ICD shocks for
      symptomatic VT. There was an average of 2.3 shocks (range 1-4 shocks), and the
      mean time to first shock post-device implantation was 3.6 years (range 2.9-4.3
      years). Among patients with negative pre- or post-PVR EPS results, 2 had VT
      requiring radiofrequency ablation and/or subsequent ICD implantation. There were
      no arrhythmic deaths. CONCLUSION: A pre-PVR EPS identified patients with higher
      risk TOF undergoing PVR. Despite empirical VT cryoablation at the time of PVR, a
      high percentage of patients remained inducible for VT. In this high-risk cohort,
      post-PVR EPS evaluation is important to identify patients at risk of VT despite
      cryoablation.

PMID- 29330131
TI  - Response of human induced pluripotent stem cell-derived cardiomyocytes to several
      pharmacological agents when intrinsic syncytial pacing is overcome by acute
      external stimulation.
AB  - We challenged human induced pluripotent stem cell-derived cardiomyocyte (hiPSC
      CM) syncytia, mainly, CDI iCells with several classes of well-characterized
      pharmacological agents (including hERG blocker, Nav1.5 blocker, Cav1.2 blocker
      and opener, beta-adrenergic agonist, and If blocker) under pacing conditions,
      utilizing the Cardio-ECR instrument, a non-invasive platform featuring
      simultaneous and continuous measurement of synchronized beating rate and
      contractility (both signals were acquired simultaneously and well aligned). We
      found that: 1) with increasing acute stimulation rates (no pacing; 1, 1.5, and
      2Hz), beat interval was gradually shortened mainly in the relaxation phase of
      each beat cycle; 2) typical responses of iCells hiPSC-CMs to all tested
      pharmacological agents were either attenuated or even eliminated by pacing, in a
      concentration- and stimulation rate-dependent manner; and 3) when iCells were
      influenced by pharmacological agents and cannot follow pacing rates, they still
      beat regularly at exactly 1/2 or 1/3 of pacing rates. We concluded that when
      intrinsic syncytial pacing was overcome by faster, external stimulations, beat
      intervals of hiPSC-CMs were mainly shortened in the relaxation phase, instead of
      proportionally in each beat cycle, with increasing pacing rates. In addition, in
      response to pharmacological agents upon pacing, hiPSC-CMs exhibited distinct
      patterns of refractoriness, manifested by skipped beats in pacing-rate dependent
      manner, and attenuation (or even abolition) of the typical response evoked under
      spontaneous beating.

PMID- 29330132
TI  - An overview of the safety pharmacology society strategic plan.
AB  - Safety Pharmacology studies are conducted to characterize the confidence by which
      biologically active new chemical entities (NCE) may be anticipated as safe. Non
      clinical safety pharmacology studies aim to detect and characterize potentially
      undesirable pharmacodynamic activities using an array of in silico, in vitro and
      in vivo animal models. While a broad spectrum of methodological innovation and
      advancement of the science occurs within the Safety Pharmacology Society, the
      society also focuses on partnerships with health authorities and technology
      providers and facilitates interaction with organizations of common interest such
      as pharmacology, physiology, neuroscience, cardiology and toxicology. Education
      remains a primary emphasis for the society through content derived from regional
      and annual meetings, webinars and publication of its works it seeks to inform the
      general scientific and regulatory community. In considering the future of safety
      pharmacology the society has developed a strategy to successfully navigate
      forward and not be mired in stagnation of the discipline. Strategy can be defined
      in numerous ways but generally involves establishing and setting goals,
      determining what actions are needed to achieve those goals, and mobilizing
      resources within the society to accomplish the actions. The discipline remains in
      rapid evolution and its coverage is certain to expand to provide better guidance
      for more systems in the next few years. This overview from the Safety
      Pharmacology Society will outline the strategic plan from 2016 to 2018 and beyond
      and provide insight into the future of the discipline which builds upon a
      previous strategic plan established in 2009.

PMID- 29330133
TI  - The evaluation of drug-induced changes in left ventricular function in
      pentobarbital-anesthetized dogs.
AB  - INTRODUCTION: The goal of this study was to determine whether assessment of
      myocardial contractility and hemodynamics in an anesthetized dog model, could
      consistently detect drug-induced changes in the inotropic state of the heart
      using drugs known to have clinically relevant positive and negative effects on
      myocardial contractility. METHODS: Derived parameters included: diastolic,
      systolic and mean arterial BP, peak systolic LVP, HR, end-diastolic LVP, and
      LVdP/dtmax as the primary contractility index. RESULTS: These results demonstrate
      that statistically significant increases (amrinone and pimobendan) and decreases
      (atenolol and itraconazole) in left ventricular dP/dtmax were observed at
      clinically relevant exposures. DISCUSSION: The analysis from the current study
      supports the strategic use of the anesthetized dog model early in the drug
      Discovery process for a comprehensive cardiovascular evaluation that can include
      left ventricular dP/dtmax with good translation to human.

PMID- 29330134
TI  - A supplementary functional connectivity microstate attached to the default mode
      network in depression revealed by resting-state magnetoencephalography.
AB  - Default mode network (DMN) has discernable involvement in the representation of
      negative, self-referential information in depression. Both increased and
      decreased resting-state functional connectivity between the anterior and
      posterior DMN have been observed in depression. These conflicting connectivity
      differences necessitated further exploration of the resting-state DMN dysfunction
      in depression. Hence, we investigated the time-varying dynamic interactions
      within the DMN via functional connectivity microstates in a sub-second level. 25
      patients with depression and 25 matched healthy controls were enrolled in the MEG
      analysis. Spherical K-means algorithms embedded within an iterative optimization
      frame were applied to sliding windowed correlation matrices, resulting in sub
      second alternations of two functional connectivity microstates for groups and
      highlighting the presence of functional variability. In the power dominant state,
      depressed patients showed a transient decreased pattern that reflected
      inter/intra-subnetwork deregulation. A supplementary negatively correlated state
      simultaneously presented with increased connectivity between the ventromedial
      prefrontal cortex (vmPFC) and the posterior cingulate cortex (PCC), two core
      nodes for the anterior and posterior DMN respectively. Additionally, depressed
      patients stayed longer in the supplementary microstate compared to healthy
      controls. During the time spent in the supplementary microstate, an attempt to
      compensate for the aberrant effect of vmPFC on PCC across DMN subnetworks was
      possibly made to balance the self-related processes disturbed by the dominant
      pattern. The functional compensation mechanism of the supplementary microstate
      attached to the dominant disrupted one provided a possible explanation to the
      existing inconsistent findings between the anterior and posterior DMN in
      depression.

PMID- 29330135
TI  - APBB2 is associated with amphetamine use and plasma beta-amyloids in patients
      receiving methadone maintenance treatment.
AB  - APBB2, amyloid beta (A4) precursor protein-binding family B member 2, has been
      reported to be associated with opioid dependence. In this study, we reported the
      first time that the genetic variants in the APBB2 gene were associated with use
      of amphetamine in opioid dependent patients undergoing methadone maintenance
      treatment (MMT). 344 heroin-dependent patients undergoing MMT were recruited and
      assessed for use of amphetamine and opioids by urine toxicology, withdrawal
      severity, and side effects. DNAs were genome-widely genotyped for all patients.
      Single nucleotide polymorphisms (SNPs) in APBB2 were selected for association
      analyses for methadone treatment responses. Gene expression levels of APBB2 were
      measured by real-time polymerase chain reaction (PCR) in the EBV-transformed
      lymphoblastoids from patients. MMT patients who used amphetamine showed a
      significantly higher percentage of positive results in the urine morphine test
      (P=0.005), and insomnia (P=0.018). In single locus association analyses, SNPs
      rs3935357 and rs4861075 located at intron 6 were significantly associated with
      amphetamine use in both genotype and allele type (general linear model (GLM),
      P=0.0003, and 0.0002 for genotype, and 0.0003, and 0.002 for allele type,
      respectively). The major allele type carriers had twice risk of amphetamine use
      compared to the minor allele type carriers. Subjects with the TT genotype of
      rs4861075 showed significantly higher levels of APBB2 gene expression in both
      total (P=0.02) and long-form (P=0.037) than those with CC genotype. Detailed
      mechanisms underlying the association of APBB2 with amphetamine use and level of
      plasma amyloid beta in MMT patients require further investigation.

PMID- 29330136
TI  - White matter volume loss in amyotrophic lateral sclerosis: A meta-analysis of
      voxel-based morphometry studies.
AB  - Structural neuroimaging studies of white matter (WM) volume in amyotrophic
      lateral sclerosis (ALS) using voxel-based morphometry (VBM) have yielded
      inconsistent findings. This study aimed to perform a quantitative voxel-based
      meta-analysis using effect-size signed differential mapping (ES-SDM) to establish
      a statistical consensus between published studies for WM volume alterations in
      ALS. The pooled meta-analysis revealed significant WM volume losses in the
      bilateral supplementary motor areas (SMAs), bilateral precentral gyri (PGs), left
      middle cerebellar peduncle and right cerebellum in patients with ALS, involving
      the corticospinal tract (CST), interhemispheric fibers, subcortical arcuate
      fibers, projection fibers to the striatum and cortico-ponto-cerebellar tract. The
      meta-regression showed that the ALS functional rating scale-revised (ALSFRS-R)
      was positively correlated with decreased WM volume in the bilateral SMAs, whereas
      illness duration was negatively correlated with WM volume reduction in the right
      SMA. This study provides a thorough profile of WM volume loss in ALS and robust
      evidence that ALS is a multisystem neurodegenerative disease that involves a
      variety of subcortical WM tracts extending beyond motor cortex involvement.

PMID- 29330137
TI  - The intersection of stress and reward: BNST modulation of aversive and appetitive
      states.
AB  - The bed nucleus of the stria terminalis (BNST) is widely acknowledged as a brain
      structure that regulates stress and anxiety states, as well as aversive and
      appetitive behaviours. The diverse roles of the BNST are afforded by its highly
      modular organisation, neurochemical heterogeneity, and complex intrinsic and
      extrinsic circuitry. There has been growing interest in the BNST in relation to
      psychopathologies such as anxiety and addiction. Although research on the human
      BNST is still in its infancy, there have been extensive preclinical studies
      examining the molecular signature and hodology of the BNST and their involvement
      in stress and reward seeking behaviour. This review examines the neurochemical
      phenotype and connectivity of the BNST, as well as electrophysiological
      correlates of plasticity in the BNST mediated by stress and/or drugs of abuse.

PMID- 29330138
TI  - A biogeographic and ecological perspective to the evolution of reproductive
      behaviour in the family Salamandridae.
AB  - Amphibians have a complex reproductive behaviour, which shows the highest
      diversity among tetrapodes. The family Salamandridae, distributed across the
      entire Holarctic, is one of the most diverse groups of extant salamanders
      comprising 114 species in 21 genera. The family has a remarkable diversity of
      courtship modes, amplexus and sperm transfer. It is often hypothesised that this
      diversity has evolved in adaptation to a specific mating and/or breeding habitat.
      We test this hypothesis based upon a phylogenetic reconstruction using the
      complete mitochondrial genome sequences of 45 Salamandridae species, representing
      all existing genera. We used ancestral character state reconstruction methods and
      geographic range models and applied relaxed Bayesian molecular clock models to
      discuss the results in a temporal framework of Salamandridae evolution. Our
      results show that the family Salamandridae started to diversify in the Late
      Cretaceous (ca. 87 mya) and is of Western Palearctic origin. Ancestral character
      state reconstruction predicts that its common ancestor was oviparous, mated on
      land without amplexus and probably showed a pin wheel spermatophore transfer,
      which is still found in the Italian endemic Salamandrina terdigidata. Our results
      suggest that several colonization of continents with subsequent radiations took
      place, once to the Nearctic and twice into Eastern Asian realms. However, these
      events were only in one case associated with a change in mating behaviour (dorsal
      amplexus in Nearctic newts). Around the Cretaceous-Paleogene boundary (K-Pg
      boundary) several Salamandridae lineages further diverged, again with no obvious
      changes in mating behaviour. Overall, there is no significant signal for mating
      character evolution being caused by changes in habitat type, with only a slight
      tendency that changes in mating habitat might have led to changes in the type of
      sperm transfer which in turn was associated with changes in the presence or
      absence of amplexus.

PMID- 29330139
TI  - Phylogenomics offers resolution of major tunicate relationships.
AB  - Tunicata, a diverse clade of approximately 3000 described species of marine,
      filter-feeding chordates, is of great interest to researchers because tunicates
      are the closest living relatives of vertebrates and they facilitate comparative
      studies of our own biology. The group also includes numerous invasive species
      that cause considerable economic damage and some species of tunicates are edible.
      Despite their diversity and importance, relationships among major lineages of
      Tunicata are not completely resolved. Here, we supplemented public data with
      transcriptomes from seven species spanning the diversity of Tunicata and
      conducted phylogenomic analyses on data sets of up to 798 genes. Sensitivity
      analyses were employed to examine the influences of reducing compositional
      heterogeneity and branch-length heterogeneity. All analyses maximally supported a
      monophyletic Tunicata within Olfactores (Vertebrata + Tunicata). Within Tunicata,
      all analyses recovered Appendicularia sister to the rest of Tunicata and
      confirmed (with maximal support) that Thaliacea is nested within Ascidiacea.
      Stolidobranchia is the sister taxon to all other tunicates except Appendicularia.
      In most analyses, phlebobranch tunicates were recovered paraphyletic with respect
      to Aplousobranchia. Support for this topology varied but was strong in some
      cases. However, when only the 50 best genes based on compositional heterogeneity
      were analysed, we recovered Phlebobranchia and Aplousobranchia reciprocally
      monophyletic with strong support, consistent with most traditional morphology
      based hypotheses. Examination of internode certainty also cast doubt on results
      of phlebobranch paraphyly, which may be due to limited taxon sampling. Taken
      together, these results provide a higher-level phylogenetic framework for our
      closest living invertebrate relatives.

PMID- 29330140
TI  - Exploring Entertainment Medicine and Professionalization of Self-Care: Interview
      Study Among Doctors on the Potential Effects of Digital Self-Tracking.
AB  - BACKGROUND: Nowadays, digital self-tracking devices offer a plethora of
      possibilities to both healthy and chronically ill users who want to closely
      examine their body. This study suggests that self-tracking in a private setting
      will lead to shifting understandings in professional care. To provide more
      insight into these shifts, this paper seeks to lay bare the promises and
      challenges of self-tracking while staying close to the everyday professional
      experience of the physician. OBJECTIVE: The aim of this study was to (1) offer an
      analysis of how medical doctors evaluate self-tracking methods in their practice
      and (2) explore the anticipated shifts that digital self-care will bring about in
      relation to our findings and those of other studies. METHODS: A total of 12 in
      depth semistructured interviews with general practitioners (GPs) and
      cardiologists were conducted in Flanders, Belgium, from November 2015 to November
      2016. Thematic analysis was applied to examine the transcripts in an iterative
      process. RESULTS: Four major themes arose in our body of data: (1) the patient as
      health manager, (2) health obsession and medicalization, (3) information
      management, and (4) shifting roles of the doctors and impact on the health care
      organization. Our research findings show a nuanced understanding of the
      potentials and pitfalls of different forms of self-tracking. The necessity of
      contextualization of self-tracking data and a professionalization of self-care
      through digital devices come to the fore as important overarching concepts.
      CONCLUSIONS: This interview study with Belgian doctors examines the potentials
      and challenges of self-monitoring while focusing on the everyday professional
      experience of the physician. The dialogue between our dataset and the existing
      literature affords a fine-grained image of digital self-care and its current
      meaning in a medical-professional landscape.

PMID- 29330141
TI  - Novel Care Pathway for Patients Presenting to the Emergency Department With
      Atrial Fibrillation.

PMID- 29330142
TI  - Checklists and Circulation: Cardiovascular Quality and Outcomes.

PMID- 29330143
TI  - Breast Cancer Targeting through Inhibition of the Endoplasmic Reticulum-Based
      Apoptosis Regulator Nrh/BCL2L10.
AB  - Drug resistance and metastatic relapse remain a top challenge in breast cancer
      treatment. In this study, we present preclinical evidence for a strategy to
      eradicate advanced breast cancers by targeting the BCL-2 homolog Nrh/BCL2L10,
      which we discovered to be overexpressed in >45% of a large cohort of breast
      invasive carcinomas. Nrh expression in these tumors correlated with reduced
      metastasis-free survival, and we determined it to be an independent marker of
      poor prognosis. Nrh protein localized to the endoplasmic reticulum. Mechanistic
      investigations showed that Nrh made BH4 domain-dependent interactions with the
      ligand-binding domain of the inositol-1,4,5-triphosphate receptor (IP3R), a type
      1/3 Ca2+ channel, allowing Nrh to negatively regulate ER-Ca2+ release and to
      mediate antiapoptosis. Notably, disrupting Nrh/IP3R complexes by BH4 mimetic
      peptides was sufficient to inhibit the growth of breast cancer cells in vitro and
      in vivo Taken together, our results highlighted Nrh as a novel prognostic marker
      and a candidate therapeutic target for late stage breast cancers that may be
      addicted to Nrh.Significance: These findings offer a comprehensive molecular
      model for the activity of Nrh/BCL2L10, a little studied antiapoptotic molecule,
      prognostic marker, and candidate drug target in breast cancer. Cancer Res; 78(6);
      1404-17. (c)2018 AACR.

PMID- 29330145
TI  - MBD2 Ablation Impairs Lymphopoiesis and Impedes Progression and Maintenance of T
      ALL.
AB  - Aberrant DNA methylation patterns in leukemia might be exploited for therapeutic
      targeting. In this study, we employed a genetically deficient mouse model to
      explore the role of the methylated DNA binding protein MBD2 in normal and
      malignant hematopoiesis. MBD2 ablation led to diminished lymphocytes. Functional
      defects of the lymphoid compartment were also observed after in vivo
      reconstitution of MBD2-deficient hematopoietic stem cells (HSC). In an
      established model of Notch1-driven T-cell acute lymphoblastic leukemia (T-ALL),
      MBD2 ablation impeded malignant progression and maintenance by attenuating the
      Wnt signaling pathway. In clinical specimens of human T-ALL, Wnt signaling
      pathway signatures were significantly enhanced and positively correlated with the
      expression and function of MBD2. Furthermore, a number of typical Wnt signaling
      inhibitory genes were abnormally hypermethylated in primary human T-ALL. Abnormal
      activation of Wnt signaling in T-ALL was switched off by MBD2 deletion, partially
      by reactivating epigenetically silenced Wnt signaling inhibitors. Taken together,
      our results define essential roles for MBD2 in lymphopoiesis and T-ALL and
      suggest MBD2 as a candidate therapeutic target in T-ALL.Significance: This study
      highlights a methylated DNA binding protein as a candidate therapeutic target to
      improve the treatment of T-cell acute lymphoblastic leukemias, as a new starting
      point for developing epigenetic therapy in this and other lymphoid malignancies.
      Cancer Res; 78(7); 1632-42. (c)2018 AACR.

PMID- 29330146
TI  - Demethylation-Induced Overexpression of Shc3 Drives c-Raf-Independent Activation
      of MEK/ERK in HCC.
AB  - Invasion and intrahepatic metastasis are major factors of poor prognosis in
      patients with hepatocellular carcinoma (HCC). In this study, we show that
      increased Src homolog and collagen homolog 3 (Shc3) expression in malignant HCC
      cell lines associate with HCC invasion and metastasis. Shc3 (N-Shc) was
      significantly upregulated in tumors of 33 HCC patient samples as compared with
      adjacent normal tissues. Further analysis of 52 HCC patient samples showed that
      Shc3 expression correlated with microvascular invasion, cancer staging, and poor
      prognosis. Shc3 interacted with major vault protein, resulting in activation of
      MEK1/2 and ERK1/2 independently of Shc1 and c-Raf; this interaction consequently
      induced epithelial-mesenchymal transition and promoted HCC cell proliferation and
      metastasis. The observed increase in Shc3 levels was due to demethylation of its
      upstream promoter, which allowed c-Jun binding. In turn, Shc3 expression promoted
      c-Jun phosphorylation in a positive feedback loop. Analysis of metastasis using a
      tumor xenograft mouse model further confirmed the role of Shc3 in vivo Taken
      together, our results indicate the importance of Shc3 in HCC progression and
      identify Shc3 as a novel biomarker and potential therapeutic target in
      HCC.Significance: Ectopic expression of Shc3 forms a complex with MVP/MEK/ERK to
      potentiate ERK activation and plays an important role in sorafinib resistance in
      HCC. Cancer Res; 78(9); 2219-32. (c)2018 AACR.

PMID- 29330144
TI  - Kindlin-1 Promotes Pulmonary Breast Cancer Metastasis.
AB  - In breast cancer, increased expression of the cytoskeletal adaptor protein
      Kindlin-1 has been linked to increased risks of lung metastasis, but the
      functional basis is unknown. Here, we show that in a mouse model of polyomavirus
      middle T antigen-induced mammary tumorigenesis, loss of Kindlin-1 reduced early
      pulmonary arrest and later development of lung metastasis. This phenotype relied
      on the ability of Kindlin-1 to bind and activate beta integrin heterodimers.
      Kindlin-1 loss reduced alpha4 integrin-mediated adhesion of mammary tumor cells
      to the adhesion molecule VCAM-1 on endothelial cells. Treating mice with an anti
      VCAM-1 blocking antibody prevented early pulmonary arrest. Kindlin-1 loss also
      resulted in reduced secretion of several factors linked to metastatic spread,
      including the lung metastasis regulator tenascin-C, showing that Kindlin-1
      regulated metastatic dissemination by an additional mechanism in the tumor
      microenvironment. Overall, our results show that Kindlin-1 contributes
      functionally to early pulmonary metastasis of breast cancer.Significance: These
      findings provide a mechanistic proof in mice that Kindin-1, an integrin-binding
      adaptor protein, is a critical mediator of early lung metastasis of breast
      cancer. Cancer Res; 78(6); 1484-96. (c)2018 AACR.

PMID- 29330147
TI  - Genetic Ablation of Rbm38 Promotes Lymphomagenesis in the Context of Mutant p53
      by Downregulating PTEN.
AB  - Mutant p53 exerts gain-of-function effects that drive metastatic progression and
      therapeutic resistance, but the basis for these effects remain obscure. The RNA
      binding protein RBM38 limits translation of mutant p53 and is often altered in
      tumors harboring it. Here we show how loss of Rbm38 significantly alters cancer
      susceptibility in mutant p53 knock-in mice by shortening lifespan, altering tumor
      incidence, and promoting T-cell lymphomagenesis. Loss of Rbm38 enhanced mutant
      p53 expression and decreased expression of the tumor suppressor Pten, a key
      regulator of T-cell development. Furthermore, Rbm38 was required for Pten
      expression via stabilization of Pten mRNA through an AU-rich element in its
      3'UTR. Our results suggest that Rbm38 controls T-cell lymphomagenesis by jointly
      modulating mutant p53 and Pten, with possible therapeutic implications for
      treating T-cell malignancies.Significance: An RNA-binding protein controls T-cell
      lymphomagenesis by jointly modulating mutant p53 and PTEN, with possible
      therapeutic implications for treating T-cell malignancies. Cancer Res; 78(6);
      1511-21. (c)2018 AACR.

PMID- 29330148
TI  - Correction.

PMID- 29330149
TI  - Voluntary exercise and depression-like behavior in rodents: are we running in the
      right direction?
AB  - Acute or chronic exposure to stress can increase the risk to develop major
      depressive disorder, a severe, recurrent and common psychiatric condition.
      Depression places an enormous social and financial burden on modern society.
      Although many depressed patients are treated with antidepressants, their efficacy
      is only modest, underscoring the necessity to develop clinically effective
      pharmaceutical or behavioral treatments. Exercise training produces beneficial
      effects on stress-related mental disorders, indicative of clinical potential. The
      pro-resilient and antidepressant effects of exercise training have been
      documented for several decades. Nonetheless, the underlying molecular mechanisms
      and the brain circuitries involved remain poorly understood. Preclinical
      investigations using voluntary wheel running, a frequently used rodent model that
      mimics aspects of human exercise training, have started to shed light on the
      molecular adaptations, signaling pathways and brain nuclei underlying the
      beneficial effects of exercise training on stress-related behavior. In this
      review, I highlight several neurotransmitter systems that are putative mediators
      of the beneficial effects of exercise training on mental health, and review
      recent rodent studies that utilized voluntary wheel running to promote our
      understanding of exercise training-induced central adaptations. Advancements in
      our mechanistic understanding of how exercise training induces beneficial
      neuronal adaptations will provide a framework for the development of new
      strategies to treat stress-associated mental illnesses.

PMID- 29330150
TI  - Dysfunctional signaling underlying endometriosis: current state of knowledge.
AB  - Endometriosis is defined as the presence of endometrial tissue outside the
      uterine cavity. It affects approximately 5-10% of women of reproductive age.
      Endometriosis is associated with dysmenorrhea, dyspareunia and, often, severe
      pelvic pain. In addition to pain, women with endometriosis often experience
      infertility. Defining the molecular etiology of endometriosis is a significant
      challenge for improving the quality of women's lives. Unfortunately, the
      pathophysiology of endometriosis is not well understood. Here, we summarize the
      potential causative factors of endometriosis in the following three categories:
      (1) dysregulation of immune cells in the peritoneal fluid and endometriotic
      lesions; (2) alteration of apoptotic signaling in retrograde menstrual tissue and
      cytotoxic T cells involved in endometriosis progression and (3) dysregulation of
      oxidative stress. Determining the molecular etiology of these dysregulated
      cellular signaling pathways should provide crucial clues for understanding
      initiation and progression of endometriosis. Moreover, improved understanding
      should suggest new molecular therapeutic targets that could improve the
      specificity of endometriosis treatments and reduce the side effects associated
      with current approaches.

PMID- 29330151
TI  - Interleukin-22 reverses human islet dysfunction and apoptosis triggered by
      hyperglycemia and LIGHT.
AB  - Interleukin (IL)-22 has recently been suggested as an anti-inflammatory cytokine
      that could protect the islet cells from inflammation- and glucose-induced
      toxicity. We have previously shown that the tumor necrosis factor family member,
      LIGHT, can impair human islet function at least partly via pro-apoptotic effects.
      Herein, we aimed to investigate the protective role of IL-22 on human islets
      exposed to the combination of hyperglycemia and LIGHT. First, we found
      upregulation of LIGHT receptors (LTbetaR and HVEM) in engrafted human islets
      exposed to hyperglycemia (>11 mM) for 17 days post transplantation by using a
      double islet transplantation mouse model as well as in human islets cultured with
      high glucose (HG) (20 mM glucose) + LIGHT in vitro, and this latter effect was
      attenuated by IL-22. The effect of HG + LIGHT impairing glucose-stimulated
      insulin secretion was reversed by IL-22. The harmful effect of HG + LIGHT on
      human islet function seemed to involve enhanced endoplasmic reticulum stress
      evidenced by upregulation of p-IRE1alpha and BiP, elevated secretion of pro
      inflammatory cytokines (IL-6, IL-8, IP-10 and MCP-1) and the pro-coagulant
      mediator tissue factor (TF) release and apoptosis in human islets, whereas all
      these effects were at least partly reversed by IL-22. Our findings suggest that
      IL-22 could counteract the harmful effects of LIGHT/hyperglycemia on human islet
      cells and potentially support the strong protective effect of IL-22 on impaired
      islet function and survival.

PMID- 29330152
TI  - Risk of Infection in Type 1 and Type 2 Diabetes Compared With the General
      Population: A Matched Cohort Study.
AB  - OBJECTIVE: We describe in detail the burden of infections in adults with diabetes
      within a large national population cohort. We also compare infection rates
      between patients with type 1 and type 2 diabetes mellitus (T1DM and T2DM).
      RESEARCH DESIGN AND METHODS: A retrospective cohort study compared 102,493
      English primary care patients aged 40-89 years with a diabetes diagnosis by 2008
      (n = 5,863 T1DM and n = 96,630 T2DM) with 203,518 age-sex-practice-matched
      control subjects without diabetes. Infection rates during 2008-2015, compiled
      from primary care and linked hospital and mortality records, were compared across
      19 individual infection categories. These were further summarized as any
      requiring a prescription or hospitalization or as cause of death. Poisson
      regression was used to estimate incidence rate ratios (IRRs) between 1) people
      with diabetes and control subjects and 2) T1DM and T2DM adjusted for age, sex,
      smoking, BMI, and deprivation. RESULTS: Compared with control subjects without
      diabetes, patients with diabetes had higher rates for all infections, with the
      highest IRRs seen for bone and joint infections, sepsis, and cellulitis. IRRs for
      infection-related hospitalizations were 3.71 (95% CI 3.27-4.21) for T1DM and 1.88
      (95% CI 1.83-1.92) for T2DM. A direct comparison of types confirmed higher
      adjusted risks for T1DM versus T2DM (death from infection IRR 2.19 [95% CI 1.75
      2.74]). We estimate that 6% of infection-related hospitalizations and 12% of
      infection-related deaths were attributable to diabetes. CONCLUSIONS: People with
      diabetes, particularly T1DM, are at increased risk of serious infection,
      representing an important population burden. Strategies that reduce the risk of
      developing severe infections and poor treatment outcomes are under-researched and
      should be explored.

PMID- 29330153
TI  - Heart Failure in Pregnant Women: A Concern Across the Pregnancy Continuum.
AB  - BACKGROUND: Heart failure (HF) is a leading cause of maternal morbidity and
      mortality in the United States, but prevalence, correlates, and outcomes of HF
      related hospitalization during antepartum, delivery, and postpartum periods
      remain unknown. The objective was to examine HF prevalence, correlates, and
      outcomes among pregnancy-related hospitalizations among women 13 to 49 years of
      age. METHODS AND RESULTS: We used the 2001 to 2011 Nationwide Inpatient Sample.
      Rates of HF were calculated by patient and hospital characteristics. Survey
      logistic regression was used to estimate adjusted odds ratios representing the
      association between HF and each outcome, stratified by antepartum, delivery, and
      postpartum periods. Joinpoint regression was used to describe temporal trends in
      HF and in-hospital mortality. Over 50 million pregnancy-related hospitalizations
      were analyzed. The overall rate of HF was 112 cases per 100 000 pregnancy-related
      hospitalizations. Although postpartum encounters represented only 1.5% of
      pregnancy-related hospitalizations, ~60% of HF cases occurred postpartum,
      followed by delivery (27.3%) and antepartum (13.2%). Among postpartum
      hospitalizations, there was a significant 7.1% (95% confidence interval, 4.4-9.8)
      annual increase in HF from 2001 to 2006, followed by a steady rate through 2011.
      HF rates among antepartum hospitalizations increased on average 4.9% (95%
      confidence interval, 3.0-6.8) annually from 2001 to 2011. Women with a diagnosis
      of HF were more likely to experience adverse maternal outcomes, as reflected by
      outcome-specific adjusted odds ratios during antepartum (2.7-25), delivery (6
      195), and postpartum (1.5-6.6) periods. CONCLUSIONS: HF is associated with
      increased risk of maternal mortality and morbidities. During hospitalization,
      high-risk mothers need to be identified and surveillance programs developed
      before discharge.

PMID- 29330154
TI  - Novel Wearable Seismocardiography and Machine Learning Algorithms Can Assess
      Clinical Status of Heart Failure Patients.
AB  - BACKGROUND: Remote monitoring of patients with heart failure (HF) using wearable
      devices can allow patient-specific adjustments to treatments and thereby
      potentially reduce hospitalizations. We aimed to assess HF state using wearable
      measurements of electrical and mechanical aspects of cardiac function in the
      context of exercise. METHODS AND RESULTS: Patients with compensated (outpatient)
      and decompensated (hospitalized) HF were fitted with a wearable ECG and
      seismocardiogram sensing patch. Patients stood at rest for an initial recording,
      performed a 6-minute walk test, and then stood at rest for 5 minutes of recovery.
      The protocol was performed at the time of outpatient visit or at 2 time points
      (admission and discharge) during an HF hospitalization. To assess patient state,
      we devised a method based on comparing the similarity of the structure of
      seismocardiogram signals after exercise compared with rest using graph mining
      (graph similarity score). We found that graph similarity score can assess HF
      patient state and correlates to clinical improvement in 45 patients (13
      decompensated, 32 compensated). A significant difference was found between the
      groups in the graph similarity score metric (44.4+/-4.9 [decompensated HF] versus
      35.2+/-10.5 [compensated HF]; P<0.001). In the 6 decompensated patients with
      longitudinal data, we found a significant change in graph similarity score from
      admission (decompensated) to discharge (compensated; 44+/-4.1 [admitted] versus
      35+/-3.9 [discharged]; P<0.05). CONCLUSIONS: Wearable technologies recording
      cardiac function and machine learning algorithms can assess compensated and
      decompensated HF states by analyzing cardiac response to submaximal exercise.
      These techniques can be tested in the future to track the clinical status of
      outpatients with HF and their response to pharmacological interventions.

PMID- 29330155
TI  - Amlexanox Inhibits Cerebral Ischemia-Induced Delayed Astrocytic High-Mobility
      Group Box 1 Release and Subsequent Brain Damage.
AB  - High-mobility group box 1 (HMGB1) is increased in the cerebrospinal fluid (CSF)
      and serum during the early and late phases of brain ischemia and is known to
      contribute to brain damage. However, detailed characterization underlying cell
      type-specific HMGB1 release and pathophysiological roles of extracellularly
      released HMGB1 in ischemic brain remain unclear. Here, we examined cell type
      specific HMGB1 release and the therapeutic potential of amlexanox, an inhibitor
      of nonclassical release, and of an anti-HMGB1 antibody against ischemic brain
      damage. HMGB1 depletion from neuronal nuclei was observed within 3 hours after
      transient middle cerebral artery occlusion (tMCAO), whereas the
      intracerebroventricular (i.c.v.) pretreatment with amlexanox blocked HMGB1
      release from neurons, resulting in HMGB1 redistribution in the nuclei and
      cytoplasm. HMGB1 was selectively released from astrocytes 27 hours after tMCAO
      and this HMGB1 release was blocked by late treatment with amlexanox (i.c.v.) 24
      hours after tMCAO. Proximity extension assay revealed that the HMGB1 level was
      elevated in the CSF at 3 and 27 hours after tMCAO. This late treatment with
      amlexanox significantly protected the brain from ischemic damage, but its
      pretreatment 30 minutes before tMCAO failed to show any protection. The late
      treatment (i.c.v.) with anti-HMGB1 antibody 24 hours after tMCAO also ameliorated
      ischemic brain damage 48 hours after tMCAO. Thus, the inhibition of brain damage
      by late treatment with amlexanox or anti-HMGB1 antibody indicates that late HMGB1
      release plays a role in the maintenance of stroke-induced brain damage, and the
      inhibition of this release would be a novel therapeutic target for protection of
      ischemic brain damage.

PMID- 29330157
TI  - Measuring the prevention of harm due to minimum alcohol pricing.

PMID- 29330156
TI  - Application of Receptor Theory to the Design and Use of Fixed-Proportion Mu
      Opioid Agonist and Antagonist Mixtures in Rhesus Monkeys.
AB  - Receptor theory predicts that fixed-proportion mixtures of a competitive,
      reversible agonist (e.g., fentanyl) and antagonist (e.g., naltrexone) at a common
      receptor [e.g., mu-opioid receptors (MORs)] will result in antagonist proportion
      dependent decreases in apparent efficacy of the agonist/antagonist mixtures and
      downward shifts in mixture dose-effect functions. The present study tested this
      hypothesis by evaluating behavioral effects of fixed-proportion
      fentanyl/naltrexone mixtures in a warm-water tail-withdrawal procedure in rhesus
      monkeys (n = 4). Fentanyl (0.001-0.056 mg/kg) alone, naltrexone (0.032-1.0 mg/kg,
      i.m.) alone, and fixed-proportion mixtures of fentanyl/naltrexone (1:0.025,
      1:0.074, and 1:0.22) were administered in a cumulative-dosing procedure, and the
      proportions were based on published fentanyl and naltrexone Kd values at MOR in
      monkey brain. Fentanyl alone produced dose-dependent antinociception at both 50
      and 54 degrees C thermal intensities. Up to the largest dose tested, naltrexone
      alone did not alter nociception. Consistent with receptor theory predictions,
      naltrexone produced a proportion-dependent decrease in the effectiveness of
      fentanyl/naltrexone mixtures to produce antinociception. The maximum effects of
      fentanyl, naltrexone, and each mixture were also used to generate an efficacy
      effect scale for antinociception at each temperature, and this scale was
      evaluated for its utility in quantifying 1) efficacy requirements for
      antinociception at 50 and 54 degrees C and 2) relative efficacy of six MOR
      agonists that vary in their efficacies to produce agonist-stimuated GTPgammaS
      binding in vitro (from lowest to highest efficacy: 17-cyclopropylmethyl-3,14beta
      dihyroxy-4,5alpha-epoxy-6alpha-[(3'-isoquinolyl)acetamindo]morphine, nalbuphine,
      buprenorphine, oxycodone, morphine, and methadone). These results suggest that
      fixed-proportion agonist/antagonist mixtures may offer a useful strategy to
      manipulate apparent drug efficacy for basic research or therapeutic purposes.

PMID- 29330159
TI  - Commercial influence in control of non-communicable diseases.

PMID- 29330160
TI  - US is the most dangerous wealthy nation for a child to be born into, study
      concludes.

PMID- 29330163
TI  - Affective stimuli in behavioural interventions soliciting for health check-up
      services and the service users' socioeconomic statuses: a study at Japanese
      pachinko parlours.
AB  - : Editor's note The study reported in this article examines a health intervention
      that uses gendered stereotypes of the nursing profession and suggestive uniforms
      that play on women's sexuality to encourage people to engage in health checkups.
      The intervention was not under the control of the authors and the study was
      approved by an institutional research ethics board. The Journal of Epidemiology &
      Community Health condemns the use of sexism, gender and professional stereotypes
      and other forms of discriminatory or exploitative behaviour for any purpose,
      including health promotion programs. In light of concerns raised about this paper
      (see eLetters with this paper), we are conducting an audit of our review process
      and will put in place measures to ensure that the material we publish condemns
      sexism, racism and other forms of discrimination and embodies principles of
      inclusion and non-discrimination. BACKGROUND: Socioeconomically vulnerable people
      are likely to have more health risks because of inadequate behaviour choices
      related to chronic social stresses. Brain science suggests that stress causes
      cognitively biased automatic decision making, preferring instant stress relief
      and pleasure (eg, smoking, alcohol use and drug abuse) as opposed to reflectively
      seeking health-maintenance services (eg, health check-ups). As such, hedonic
      stimuli that nudge people towards preventive actions could reduce health
      behaviour disparities. The purpose of this intervention study was to test this
      hypothesis. METHODS: An instant health check-up service company had 320 health
      check-up sessions at pachinko (Japanese gambling) parlours; 1721 persons in
      intervention sessions and 6507 persons in control sessions received the service.
      The stimuli the company used in the intervention sessions were young women
      wearing mildly erotic nurse costumes, who solicited the pachinko players for
      health check-up services. We compared the prevalence of socioeconomically
      vulnerable individuals between the intervention and control sessions, adjusting
      for individual-level and parlour-level potential confounders. RESULTS: Even
      adjusting for health risks and within-parlour clustering, the intervention
      sessions gathered more socioeconomically vulnerable customers than the regular
      sessions. Compared with control sessions, in intervention sessions the adjusted
      prevalence ratios were 1.15 (95% CI 0.99 to 1.35) for not having a job (vs having
      a job) and 1.36 (95% CI 1.00 to 1.86) for holders of National Health Insurance
      (which includes more socially vulnerable people than other insurance programmes).
      CONCLUSION: The results supported our hypothesis. Offering health check-up
      opportunities equipped with 'tricks' that nudge people to act might be effective
      for anyone but is potentially more valuable for socially vulnerable people.
      Ethical discussions are needed to further consider the use of erotic stimuli and
      other essential drivers of human behaviour.

PMID- 29330162
TI  - Transcriptome Analyses of Mosaic (MSC) Mitochondrial Mutants of Cucumber in a
      Highly Inbred Nuclear Background.
AB  - Cucumber (Cucumis sativus L.) has a large, paternally transmitted mitochondrial
      genome. Cucumber plants regenerated from cell cultures occasionally show
      paternally transmitted mosaic (MSC) phenotypes, characterized by slower growth,
      chlorotic patterns on the leaves and fruit, lower fertility, and rearrangements
      in their mitochondrial DNAs (mtDNAs). MSC lines 3, 12, and 16 originated from
      different cell cultures all established using the highly inbred, wild-type line
      B. These MSC lines possess different rearrangements and under-represented regions
      in their mtDNAs. We completed RNA-seq on normalized and non-normalized cDNA
      libraries from MSC3, MSC12, and MSC16 to study their nuclear gene-expression
      profiles relative to inbred B. Results from both libraries indicated that gene
      expression in MSC12 and MSC16 were more similar to each other than MSC3. Forty
      one differentially expressed genes (DEGs) were upregulated and one downregulated
      in the MSC lines relative to B. Gene functional classifications revealed that
      more than half of these DEGs are associated with stress-response pathways.
      Consistent with this observation, we detected elevated levels of hydrogen
      peroxide throughout leaf tissue in all MSC lines compared to wild-type line B.
      These results demonstrate that independently produced MSC lines with different
      mitochondrial polymorphisms show unique and shared nuclear responses. This study
      revealed genes associated with stress response that could become selection
      targets to develop cucumber cultivars with increased stress tolerance, and
      further support of cucumber as a model plant to study nuclear-mitochondrial
      interactions.

PMID- 29330161
TI  - Production of BMP4 by endothelial cells is crucial for endogenous thymic
      regeneration.
AB  - The thymus is not only extremely sensitive to damage but also has a remarkable
      ability to repair itself. However, the mechanisms underlying this endogenous
      regeneration remain poorly understood, and this capacity diminishes considerably
      with age. We show that thymic endothelial cells (ECs) comprise a critical pathway
      of regeneration via their production of bone morphogenetic protein 4 (BMP4) ECs
      increased their production of BMP4 after thymic damage, and abrogating BMP4
      signaling or production by either pharmacologic or genetic inhibition impaired
      thymic repair. EC-derived BMP4 acted on thymic epithelial cells (TECs) to
      increase their expression of Foxn1, a key transcription factor involved in TEC
      development, maintenance, and regeneration, and its downstream targets such as
      Dll4, a key mediator of thymocyte development and regeneration. These studies
      demonstrate the importance of the BMP4 pathway in endogenous tissue regeneration
      and offer a potential clinical approach to enhance T cell immunity.

PMID- 29330164
TI  - Public health guide to field developments linking ecosystems, environments and
      health in the Anthropocene.
AB  - The impacts of global environmental change have precipitated numerous approaches
      that connect the health of ecosystems, non-human organisms and humans. However,
      the proliferation of approaches can lead to confusion due to overlaps in
      terminology, ideas and foci. Recognising the need for clarity, this paper
      provides a guide to seven field developments in environmental public health
      research and practice: occupational and environmental health; political ecology
      of health; environmental justice; ecohealth; One Health; ecological public
      health; and planetary health. Field developments are defined in terms of their
      uniqueness from one another, are historically situated, and core texts or
      journals are highlighted. The paper ends by discussing some of the intersecting
      features across field developments, and considers opportunities created through
      such convergence. This field guide will be useful for those seeking to build a
      next generation of integrative research, policy, education and action that is
      equipped to respond to current health and sustainability challenges.

PMID- 29330165
TI  - Survival in relation to multimorbidity patterns in older adults in primary care
      in Barcelona, Spain (2010-2014): a longitudinal study based on electronic health
      records.
AB  - BACKGROUND: Several studies have analysed the characteristics of multimorbidity
      patterns but none have evaluated the relationship with survival. The purpose of
      this study was to compare survival across older adults with different chronic
      multimorbidity patterns (CMPs). METHODS: Prospective longitudinal observational
      study using electronic health records for 190 108 people aged >=65 years in
      Barcelona, Spain (2009-2014). CMPs were identified by cluster analysis. Mortality
      rates were estimated using the Catalan population structure and individual time
      at risk. Survival according to CMP (Cox regression) was analysed using hazard
      ratios (HRs) and 95% confidence intervals (CIs) with stratification by sex and
      age group (65-79, 80-94) and adjustment for age at onset, deprivation index,
      number of chronic conditions and invoiced drugs. RESULTS: The highest mortality
      rates were observed in men, adults aged 80-94 years, socially disadvantaged
      quintiles and people prescribed more drugs and with fewer conditions. Using the
      musculoskeletal pattern as the reference category, men with the digestive
      respiratory pattern had a higher risk of death, with adjusted HRs of 6.16 (95% CI
      5.37 to 7.06) in the 65-79 age group and 2.62 (95% CI 2.31 to 2.97) in the 80-94
      age group. In women, the cardiovascular pattern was associated with the highest
      risk, with adjusted HRs of 6.34 (95% CI 5.28 to 7.61) in the 65-79 age group and
      3.05 (95% CI 2.73 to 3.41) in the 80-94 age group. These patterns were also
      associated with the highest mortality rates. CONCLUSIONS: Mortality and survival
      vary according to CMPs in older adults stratified by sex and age. Our findings
      are useful for guiding the design and implementation of clinical management
      strategies.

PMID- 29330166
TI  - Impact of free access to leisure facilities and community outreach on
      inequalities in physical activity: a quasi-experimental study.
AB  - BACKGROUND: There are large inequalities in levels of physical activity in the
      UK, and this is an important determinant of health inequalities. Little is known
      about the effectiveness of community-wide interventions to increase physical
      activity and whether effects differ by socioeconomic group. METHODS: We conducted
      interrupted time series and difference-in-differences analyses using local
      administrative data and a large national survey to investigate the impact of an
      intervention providing universal free access to leisure facilities alongside
      outreach and marketing activities in a deprived local authority area in the
      northwest of England. Outcomes included attendances at swimming and gym sessions,
      self-reported participation in gym and swim activity and any physical activity.
      RESULTS: The intervention was associated with a 64% increase in attendances at
      swimming and gym sessions (relative risk 1.64, 95% CI 1.43 to 1.89, P<0.001), an
      additional 3.9% of the population participating in at least 30 min of moderate
      intensity gym or swim sessions during the previous four weeks (95% CI 3.6 to 4.1)
      and an additional 1.9% of the population participating in any sport or active
      recreation of at least moderate intensity for at least 30 min on at least 12 days
      out of the last four weeks (95% CI 1.7 to 2.1). The effect on gym and swim
      activity and overall levels of participation in physical activity was
      significantly greater for the more disadvantaged socioeconomic group.
      CONCLUSIONS: The study suggests that removing user charges from leisure
      facilities in combination with outreach and marketing activities can increase
      overall population levels of physical activity while reducing inequalities.

PMID- 29330167
TI  - Differences in declining mortality rates due to coronary heart disease by
      neighbourhood deprivation.
AB  - BACKGROUND: Cardiovascular disease (CVD) is the main cause of death in most
      industrialised countries, including those in Europe. The mortality rates due to
      coronary heart disease (CHD), one of the most serious CVD conditions, have been
      decreasing in most European countries during the last decades. However, whether
      the trends over time in CHD mortality rates differ depending on neighbourhood
      deprivation has rarely been investigated. METHODS: For each year of the study
      period, 1988-2012, in Sweden, age-standardised mortality rates were calculated
      for three different types of neighbourhoods, characterised by a Neighbourhood
      Deprivation Index. Joinpoint regression was used to investigate potential changes
      in age-standardised mortality rates by neighbourhood deprivation and over time.
      RESULTS: Over the study period, age-standardised mortality rates due to CHD were
      consistently the highest in the deprived neighbourhoods and the lowest in the
      affluent neighbourhoods. We observed a statistically significant overall decline,
      ranging from 67% to 59%, in the age-standardised CHD mortality rates for each
      level of neighbourhood deprivation. Furthermore, the decline for the affluent
      neighbourhoods was significantly higher compared with the decline in the deprived
      neighbourhoods. CONCLUSION: Age-standardised CHD mortality rates decreased
      significantly in Sweden between 1988 and 2012. This decline was more pronounced
      in the affluent neighbourhoods, which indicates that the improvements in
      prevention and treatment of CHD have not benefited individuals residing in
      deprived neighbourhoods to an equal extent. Knowledge of time trends in CHD
      mortality by level of neighbourhood deprivation may help guide decision-makers in
      the development of appropriate healthcare policies for deprived neighbourhoods.

PMID- 29330169
TI  - Inter-rater reliability in the Paediatric Observation Priority Score (POPS).
AB  - OBJECTIVE: The primary objective of this study was to determine the level of
      inter-rater reliability between nursing staff for the Paediatric Observation
      Priority Score (POPS). DESIGN: Retrospective observational study. SETTING: Single
      centre paediatric emergency department. PARTICIPANTS: 12 participants from a
      convenience sample of 21 nursing staff. INTERVENTIONS: Participants were shown
      video footage of three pre-recorded paediatric assessments and asked to record
      their own POPS for each child. The participants were blinded to the original, in
      person POPS. Further data were gathered in the form of a questionnaire to
      determine the level of training and experience the candidate had using the POPS
      score prior to undertaking this study. MAIN OUTCOME MEASURES: Inter-rater
      reliability among participants scoring of the POPS. RESULTS: Overall kappa value
      for case 1 was 0.74 (95% CI 0.605 to 0.865), case 2 was 1 (perfect agreement) and
      case 3 was 0.66 (95% CI 0.58 to 0.744). CONCLUSION: This study suggests there is
      good inter-rater reliability between different nurses' use of POPS in assessing
      sick children in the emergency department.

PMID- 29330170
TI  - Retrospective review of Synacthen testing in infants.
AB  - BACKGROUND: A subnormal cortisol response (30 min level (C30min)<550 nmol/L) to
      synthetic adrenocorticotrophic hormone/Synacthen test (SDST) in all infants does
      not necessarily indicate underlying or persistent hypothalamic-pituitary-adrenal
      axis pathology. METHODS: We retrospectively evaluated the diagnoses and outcomes
      in 68 infants who had a SDST at age <6 months from 2011 to 2014. RESULTS: 29
      (43%) infants had a subnormal SDST. Causative pathology was identified in 9/29
      (31%). In 20/29 (69%) with no identified pathology, repeat SDST was normal in
      18/20 (90%) at median age 0.6 (range 0.1-3.2) years but persistently subnormal in
      2. Those with a transient abnormality were more likely to be small for
      gestational age (P=0.03) and had higher initial SDST C30min (390 nmol/L vs 181
      nmol/L, P=0.01) than those with pathology. CONCLUSION: Specific aetiology can be
      identified in a third of infants with a subnormal SDST. When the aetiology
      remains elusive, adrenal function should be reassessed as the problem can be
      transient.

PMID- 29330168
TI  - MRB7260 is essential for productive protein-RNA interactions within the RNA
      editing substrate binding complex during trypanosome RNA editing.
AB  - The trypanosome RNA editing substrate binding complex (RESC) acts as the platform
      for mitochondrial uridine insertion/deletion RNA editing and facilitates the
      protein-protein and protein-RNA interactions required for the editing process.
      RESC is broadly comprised of two subcomplexes: GRBC (guide RNA binding complex)
      and REMC (RNA editing mediator complex). Here, we characterize the function and
      position in RESC organization of a previously unstudied RESC protein, MRB7260. We
      show that MRB7260 forms numerous RESC-related complexes, including a novel, small
      complex with the guide RNA binding protein, GAP1, which is a canonical GRBC
      component, and REMC components MRB8170 and TbRGG2. RNA immunoprecipitations in
      MRB7260-depleted cells show that MRB7260 is critical for normal RNA trafficking
      between REMC and GRBC. Analysis of protein-protein interactions also reveals an
      important role for MRB7260 in promoting stable association of the two
      subcomplexes. High-throughput sequencing analysis of RPS12 mRNAs from MRB7260
      replete and depleted cells demonstrates that MRB7260 is critical for gRNA
      exchange and early gRNA utilization, with the exception of the initiating gRNA.
      Together, these data demonstrate that MRB7260 is essential for productive protein
      RNA interactions with RESC during RNA editing.

PMID- 29330171
TI  - Historic child sexual abuse: have we got it right?

PMID- 29330172
TI  - Origins of tobacco harm reduction in the UK: the 'Product Modification Programme'
      (1972-1991).
AB  - OBJECTIVE: To better understand the current embrace of long-term nicotine
      maintenance by British governmental agencies and tobacco harm reduction by
      several leading British public health organisations, describe the context and
      deliberations of the UK's first formal tobacco risk reduction programme: 'Product
      Modification'. METHODS: Analysis of previously secret tobacco industry documents,
      news archives and Parliamentary debate records. RESULTS: From 1972 to 1991, the
      British government sought to investigate safer smoking through the 'product
      modification programme'. The Independent Scientific Committee on Smoking and
      Health (ISCSH) advised the British government on these efforts and collaborated
      with the tobacco industry, with which government then negotiated to determine
      policy. The ISCSH operated from four industry-backed premises, which contributed
      to the ISCSH's support of safer smoking: (1) reduced toxicity indicates reduced
      risk; (2) collaboration with the tobacco industry will not undermine tobacco
      control; (3) nicotine addiction is unavoidable; (4) to curtail cigarette use,
      solutions must be consumer-approved (ie, profitable). These premises often
      undermined tobacco control efforts and placed the ISCSH at odds with broader
      currents in public health. The product modification programme was abandoned in
      1991 as the European Community began requiring members to adopt upper tar limits,
      rendering the ISCSH redundant. POLICY IMPLICATIONS: Endorsements of reduced harm
      tobacco products share the same four premises that supported the product
      modification programme. Current tobacco harm reduction premises and policies
      supported by the British government and leading British public health
      organisations may reflect the historical influence of the tobacco industry.

PMID- 29330173
TI  - Seasonal variations in tuberculosis diagnosis among HIV-positive individuals in
      Southern Africa: analysis of cohort studies at antiretroviral treatment
      programmes.
AB  - OBJECTIVES: Seasonal variations in tuberculosis diagnoses have been attributed to
      seasonal climatic changes and indoor crowding during colder winter months. We
      investigated trends in pulmonary tuberculosis (PTB) diagnosis at antiretroviral
      therapy (ART) programmes in Southern Africa. SETTING: Five ART programmes
      participating in the International Epidemiology Database to Evaluate AIDS in
      South Africa, Zambia and Zimbabwe. PARTICIPANTS: We analysed data of 331 634 HIV
      positive adults (>15 years), who initiated ART between January 2004 and December
      2014. PRIMARY OUTCOME MEASURE: We calculated aggregated averages in monthly
      counts of PTB diagnoses and ART initiations. To account for time trends, we
      compared deviations of monthly event counts to yearly averages, and calculated
      correlation coefficients. We used multivariable regressions to assess
      associations between deviations of monthly ART initiation and PTB diagnosis
      counts from yearly averages, adjusted for monthly air temperatures and
      geographical latitude. As controls, we used Kaposi sarcoma and extrapulmonary
      tuberculosis (EPTB) diagnoses. RESULTS: All programmes showed monthly variations
      in PTB diagnoses that paralleled fluctuations in ART initiations, with recurrent
      patterns across 2004-2014. The strongest drops in PTB diagnoses occurred in
      December, followed by April-May in Zimbabwe and South Africa. This corresponded
      to holiday seasons, when clinical activities are reduced. We observed little
      monthly variation in ART initiations and PTB diagnoses in Zambia. Correlation
      coefficients supported parallel trends in ART initiations and PTB diagnoses
      (correlation coefficient: 0.28, 95% CI 0.21 to 0.35, P<0.001). Monthly
      temperatures and latitude did not substantially change regression coefficients
      between ART initiations and PTB diagnoses. Trends in Kaposi sarcoma and EPTB
      diagnoses similarly followed changes in ART initiations throughout the year.
      CONCLUSIONS: Monthly variations in PTB diagnosis at ART programmes in Southern
      Africa likely occurred regardless of seasonal variations in temperatures or
      latitude and reflected fluctuations in clinical activities and changes in health
      seeking behaviour throughout the year, rather than climatic factors.

PMID- 29330174
TI  - Views and experiences of seeking information and help for vitiligo: a qualitative
      study of written accounts.
AB  - OBJECTIVES: Vitiligo is a relatively common autoimmune condition causing loss of
      skin pigment. Around 1 in 100 people in the UK develop vitiligo. It can have a
      significant impact on quality of life for many of those affected. How people
      access information and help for vitiligo may influence how they manage such
      impact. We aimed to explore people's views and experiences of seeking health
      information and help for vitiligo. DESIGN: Qualitative analysis of free-text
      responses to four open-ended questions in an online survey. SETTING: Online
      survey conducted in the UK between February and March 2016. PARTICIPANTS: A
      survey link was emailed to 675 members of The Vitiligo Society, a UK-based
      charity providing information and support for people with vitiligo. One hundred
      and sixty-one members responded to the survey (24%). RESULTS: Many participants
      wrote extensive free text, often reporting frustration with help-seeking. They
      perceived general practitioners (GP) as their primary source of advice but felt
      that GPs had low awareness of available treatments. Where GPs appeared
      sympathetic or signposted towards further information this was appreciated, even
      where people felt their GP had not seemed knowledgeable. Many felt that vitiligo
      was dismissed by health professionals including GPs and dermatologists as
      'cosmetic', which upset those who experienced substantial impact. Participants
      expressed concerns about the credibility of online information on vitiligo and
      the need for reliable, detailed information, as well as a desire for support with
      managing its psychosocial impact. CONCLUSIONS: Information and help-seeking needs
      of people with vitiligo currently appear to be poorly met, even among members of
      The Vitiligo Society, who are likely to have received more information than
      others. People with vitiligo would welcome greater health professional awareness
      of available vitiligo treatments. Acknowledging the psychosocial impacts of
      vitiligo and signposting towards credible information are also welcomed.

PMID- 29330175
TI  - Development and validation of an instrument for measuring the burden of medicine
      on functioning and well-being: the Medication-Related Burden Quality of Life (MRB
      QoL) tool.
AB  - OBJECTIVE: Medication-related burden (MRB) is a negative experience with
      medicine, which may impact on psychological, social, physical and financial well
      being of an individual. This study describes the development and initial
      validation of an instrument specifically designed to measure MRB on functioning
      and well-being-the Medication-Related Burden Quality of Life (MRB-QoL) tool.
      METHODS: An initial pool of 76-items for MRB-QoL was generated. The link to MRB
      QoL survey was sent to a sample of consumers living with at least one chronic
      medical condition and taking >=3 prescription medicines on a regular basis.
      Exploratory factor analysis (EFA) was used to determine the underlining factor
      structure. Internal consistency (Cronbach's alpha) and construct validity were
      examined. The latter was examined through correlation with Medication Regimen
      Complexity Index (MRCI), Drug Burden Index (DBI) and Charlson's Comorbidity Index
      (CCI). RESULTS: 367 consumers completed the survey (51.2% male). EFA resulted in
      a 31-item, five-factor solution explaining 72% of the total variance. The five
      subscales were labelled as 'Routine and Regimen Complexity' (11 items),
      'Psychological Burden' (six items), 'Functional and Role Limitation' (seven
      items), 'Therapeutic Relationship' (three items) and 'Social Burden' (four
      items). All subscales showed good internal consistency (Cronbach's alpha 0.87 to
      0.95). Discriminant validity of MRB-QoL was demonstrated via its correlations
      with MRCI (Spearman's r -0.16 to 0.08), DBI (r 0.12 to 0.28) and CCI (r -0.23 to 
      0.15). Correlation between DBI and 'Functional and Role Limitation' subscale (r
      0.36) indicated some evidence of convergent validity. Patients with polypharmacy,
      multiple morbidity and DBI >0 had higher median scores of MRB-QoL providing
      evidence for known group validity. CONCLUSIONS: The MRB-QoL V.1 has good
      construct validity and internal consistency. The MRB-QoL may be a useful
      humanistic measure for evaluating the impact of pharmaceutical care interventions
      on patients' quality of life. Future research is warranted to further examine
      additional psychometric properties of MRB-QoL V.1 and its utility in patient
      care.

PMID- 29330176
TI  - Therapists' experiences with a new treatment combining physical exercise and
      dietary therapy (the PED-t) for eating disorders: an interview study in a
      randomised controlled trial at the Norwegian School of Sport Sciences.
AB  - OBJECTIVES: The aim of the current study is to explore how therapists running a
      guided physical exercise and dietary therapy programme (PED-t) experience their
      contribution to the treatment of patients with bulimia nervosa and binge eating
      disorder. METHODS: Ten therapists running the PED-t were semistructurally
      interviewed and the transcribed interviews were analysed using a systematic text
      condensation approach. SETTING: The study was run within the context of a
      randomised controlled trial at the Norwegian School of Sport Sciences. RESULTS:
      The therapists experienced their knowledge about physical exercise and nutrition
      as important and useful, and that they could share their knowledge with the
      patients in different ways and with confidence in their own role. They also
      believed that their knowledge could serve as tools for the patients' post
      treatment recovery and management of their daily lives. Moreover, the therapists
      put much effort in adjusting their teaching to fit each individual participant.
      Finally, they reported their personal qualities as important to build trust and
      therapeutic alliance. CONCLUSIONS: The terms 'clinical confidence' and 'alliance'
      may stand out as the overarching 'metacategories' covering the experiences
      revealed in this study. The clinical implication is that new groups of
      professionals may have an important role in the treatment of eating disorders.
      TRIAL REGISTRATION NUMBER: NCTO2079935; Results.

PMID- 29330177
TI  - Incidence of Facultative Bacterial Endosymbionts in Spider Mites Associated with
      Local Environments and Host Plants.
AB  - Spider mites are frequently associated with multiple endosymbionts whose
      infection patterns often exhibit spatial and temporal variation. However, the
      association between endosymbiont prevalence and environmental factors remains
      unclear. Here, we surveyed endosymbionts in natural populations of the spider
      mite, Tetranychus truncatus, in China, screening 935 spider mites from 21
      localities and 12 host plant species. Three facultative endosymbiont lineages,
      Wolbachia, Cardinium, and Spiroplasma, were detected at different infection
      frequencies (52.5%, 26.3%, and 8.6%, respectively). Multiple endosymbiont
      infections were observed in most local populations, and the incidence of
      individuals with the Wolbachia-Spiroplasma coinfection was higher than expected
      from the frequency of each infection within a population. Endosymbiont infection
      frequencies exhibited associations with environmental factors: Wolbachia
      infection rates increased at localities with higher annual mean temperatures,
      while Cardinium and Spiroplasma infection rates increased at localities from
      higher altitudes. Wolbachia was more common in mites from Lycopersicon esculentum
      and Glycine max compared to those from Zea mays This study highlights that host
      endosymbiont interactions may be associated with environmental factors, including
      climate and other geographically linked factors, as well as the host's food
      plant.IMPORTANCE The aim of this study was to examine the incidence of
      endosymbiont distribution and the infection patterns in spider mites. The main
      findings are that multiple endosymbiont infections were more common than expected
      and that endosymbiont infection frequencies were associated with environmental
      factors. This work highlights that host-endosymbiont interactions need to be
      studied within an environmental and geographic context.

PMID- 29330178
TI  - Development of an Efficient Genome Editing Tool in Bacillus licheniformis Using
      CRISPR-Cas9 Nickase.
AB  - Bacillus strains are important industrial bacteria that can produce various
      biochemical products. However, low transformation efficiencies and a lack of
      effective genome editing tools have hindered its widespread application.
      Recently, clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9
      techniques have been utilized in many organisms as genome editing tools because
      of their high efficiency and easy manipulation. In this study, an efficient
      genome editing method was developed for Bacillus licheniformis using a CRISPR
      Cas9 nickase integrated into the genome of B. licheniformis DW2 with
      overexpression driven by the P43 promoter. The yvmC gene was deleted using the
      CRISPR-Cas9n technique with homology arms of 1.0 kb as a representative example,
      and an efficiency of 100% was achieved. In addition, two genes were
      simultaneously disrupted with an efficiency of 11.6%, and the large DNA fragment
      bacABC (42.7 kb) was deleted with an efficiency of 79.0%. Furthermore, the
      heterologous reporter gene aprN, which codes for nattokinase in Bacillus
      subtilis, was inserted into the chromosome of B. licheniformis with an efficiency
      of 76.5%. The activity of nattokinase in the DWc9nDelta7/pP43SNT-SsacC strain
      reached 59.7 fibrinolytic units (FU)/ml, which was 25.7% higher than that of
      DWc9n/pP43SNT-SsacC Finally, the engineered strain DWc9nDelta7 (Deltaepr
      DeltawprA Deltampr DeltaaprE Deltavpr DeltabprA DeltabacABC), with multiple
      disrupted genes, was constructed using the CRISPR-Cas9n technique. Taken
      together, we have developed an efficient genome editing tool based on CRISPR
      Cas9n in B. licheniformis This tool could be applied to strain improvement for
      future research.IMPORTANCE As important industrial bacteria, Bacillus strains
      have attracted significant attention due to their production of biological
      products. However, genetic manipulation of these bacteria is difficult. The
      CRISPR-Cas9 system has been applied to genome editing in some bacteria, and
      CRISPR-Cas9n was proven to be an efficient and precise tool in previous reports.
      The significance of our research is the development of an efficient, more
      precise, and systematic genome editing method for single-gene deletion, multiple
      gene disruption, large DNA fragment deletion, and single-gene integration in
      Bacillus licheniformis via Cas9 nickase. We also applied this method to the
      genetic engineering of the host strain for protein expression.

PMID- 29330179
TI  - Influence of type-I fimbriae and fluid shear stress on bacterial behavior and
      multicellular architecture of early Escherichia coli biofilms at single-cell
      resolution.
AB  - Biofilm formation on abiotic surfaces in food and medical industry can cause
      severe contamination and infection, yet how biological and physical factors
      determine cellular architecture of early biofilms and bacterial behavior of the
      constituent cells remains largely unknown. In this study we examine the specific
      role of type-I fimbriae in nascent stages of biofilm formation and the response
      of micro-colonies to environmental flow shear at single-cell resolution. The
      results show that type-I fimbriae are not required for reversible adhesion from
      plankton, but critical for irreversible adhesion of Escherichia coli (E.coli)
      MG1655 forming biofilms on polyethylene terephthalate (PET) surfaces. Besides
      establishing a firm cell-surface contact, the irreversible adhesion seems
      necessary to initiate the proliferation of E.coli on the surface. After
      application of shear stress, bacterial retention is dominated by the 3D
      architecture of colonies independent of the population and the multi-layered
      structure could protect the embedded cells from being insulted by fluid shear,
      while cell membrane permeability mainly depends on the biofilm population and the
      duration time of the shear stress.ImportanceBacterial biofilms could lead to
      severe contamination problems in medical devices and food processing equipment.
      However, biofilms are usually studied at a rough macroscopic level, thus little
      is known about how individual bacterial behavior within biofilms and
      multicellular architecture are influenced by bacterial appendages (e.g.
      pili/fimbriae) and environmental factors during early biofilm formation. We apply
      Confocal Laser Scanning Microscopy (CLSM) to visualize E.coli micro-colonies at
      single-cell resolution. Our findings suggest that type-I fimbriae are vital to
      the initiation of bacterial proliferation on surfaces and that the responses of
      biofilm architecture and cell membrane permeability of constituent bacteria to
      fluid shear stress are different, which are respectively regulated by the 3D
      morphology and the population of micro-colonies.

PMID- 29330180
TI  - Intraclade Variability in Toxin Production and Cytotoxicity of Bacillus cereus
      Group Type Strains and Dairy-Associated Isolates.
AB  - While some species in the Bacillus cereus group are well-characterized human
      pathogens (e.g., B. anthracis and B. cereus sensu stricto), the pathogenicity of
      other species (e.g., B. pseudomycoides) either has not been characterized or is
      presently not well understood. To provide an updated characterization of the
      pathogenic potential of species in the B. cereus group, we classified a set of 52
      isolates, including 8 type strains and 44 isolates from dairy-associated sources,
      into 7 phylogenetic clades and characterized them for (i) the presence of toxin
      genes, (ii) phenotypic characteristics used for identification, and (iii)
      cytotoxicity to human epithelial cells. Overall, we found that B. cereus toxin
      genes are broadly distributed but are not consistently present within individual
      species and/or clades. After growth at 37 degrees C, isolates within a clade did
      not typically show a consistent cytotoxicity phenotype, except for isolates in
      clade VI (B. weihenstephanensis/B. mycoides), where none of the isolates were
      cytotoxic, and isolates in clade I (B. pseudomycoides), which consistently
      displayed cytotoxic activity. Importantly, our study highlights that B.
      pseudomycoides is cytotoxic toward human cells. Our results indicate that the
      detection of toxin genes does not provide a reliable approach to predict the
      pathogenic potential of B. cereus group isolates, as the presence of toxin genes
      is not always consistent with cytotoxicity phenotype. Overall, our results
      suggest that isolates from multiple B. cereus group clades have the potential to
      cause foodborne illness, although cytotoxicity is not always consistently found
      among isolates within each clade.IMPORTANCE Despite the importance of the
      Bacillus cereus group as a foodborne pathogen, characterizations of the
      pathogenic potential of all B. cereus group species were lacking. We show here
      that B. pseudomycoides (clade I), which has been considered a harmless
      environmental microorganism, produces toxins and exhibits a phenotype consistent
      with the production of pore-forming toxins. Furthermore, B. mycoides/B.
      weihenstephanensis isolates (clade VI) did not show cytotoxicity when grown at 37
      degrees C, despite carrying multiple toxin genes. Overall, we show that the
      current standard methods to characterize B. cereus group isolates and to detect
      the presence of toxin genes are not reliable indicators of species, phylogenetic
      clades, or an isolate's cytotoxic capacity, suggesting that novel methods are
      still needed for differentiating pathogenic from nonpathogenic species within the
      B. cereus group. Our results also contribute data that are necessary to
      facilitate risk assessments and a better understanding as to which B. cereus
      group species are likely to cause foodborne illness.

PMID- 29330181
TI  - A Novel Corynebacterium glutamicum l-Glutamate Exporter.
AB  - Besides metabolic pathways and regulatory networks, transport systems are also
      pivotal for cellular metabolism and hyperproduction of biochemicals using
      microbial cell factories. The identification and characterization of transporters
      are therefore of great significance for the understanding and engineering of
      transport reactions. Herein, a novel l-glutamate exporter, MscCG2, which exists
      extensively in Corynebacterium glutamicum strains but is distinct from the only
      known l-glutamate exporter, MscCG, was discovered in an industrial l-glutamate
      producing C. glutamicum strain. MscCG2 was predicted to possess three
      transmembrane helices in the N-terminal region and located in the cytoplasmic
      membrane, which are typical structural characteristics of the mechanosensitive
      channel of small conductance. MscCG2 has a low amino acid sequence identity (23%)
      to MscCG and evolved separately from MscCG with four transmembrane helices.
      Despite the considerable differences between MscCG2 and MscCG in sequence and
      structure, gene deletion and complementation confirmed that MscCG2 also
      functioned as an l-glutamate exporter and an osmotic safety valve in C.
      glutamicum Besides, transcriptional analysis showed that MscCG2 and MscCG genes
      were transcribed in similar patterns and not induced by l-glutamate-producing
      conditions. It was also demonstrated that MscCG2-mediated l-glutamate excretion
      was activated by biotin limitation or penicillin treatment and that constitutive
      l-glutamate excretion was triggered by a gain-of-function mutation of MscCG2
      (A151V). Discovery of MscCG2 will enrich the understanding of bacterial amino
      acid transport and provide additional targets for exporter engineering.IMPORTANCE
      The exchange of matter, energy, and information with surroundings is fundamental
      for cellular metabolism. Therefore, studying transport systems that are essential
      for these processes is of great significance. Besides, transport systems of
      bacterial cells are usually related to product excretion as well as product
      reuptake, making transporter engineering a useful strategy for strain
      improvement. The significance of our research is in identifying and
      characterizing a novel l-glutamate exporter from the industrial workhorse
      Corynebacterium glutamicum, which will enrich the understanding of l-glutamate
      excretion and provide a new target for studying bacterial amino acid transport
      and engineering transport reactions.

PMID- 29330182
TI  - Fluorescence Recovery Allows the Implementation of a Fluorescence Reporter Gene
      Platform Applicable for the Detection and Quantification of Horizontal Gene
      Transfer in Anoxic Environments.
AB  - The study of horizontal gene transfer (HGT) in microbial communities has been
      revolutionized by significant advances in cultivation-independent methods based
      on fluorescence reporter gene technologies. Recently, the combination of these
      novel approaches with flow cytometry has presented itself as one of the most
      powerful tools to study the spread of mobile genetic elements (MGEs) in the
      environment. However, the use of fluorescent markers, like green fluorescent
      protein (GFP) and mCherry, is limited by environmental constraints, such as
      oxygen availability and pH levels, that affect the correct maturation of their
      fluorophores. Few studies have characterized the effects of such environmental
      conditions in a systematic way, and the sheer amount of distinct protein variants
      requires each system to be examined in an individual fashion. The lack of
      efficient and reliable markers to monitor HGT in anaerobic environments, coupled
      to the abundance of ecologically and clinically relevant oxygen-deprived niches
      in which bacteria thrive, calls for the urgent development of suitable tools that
      permit its study. In an attempt to devise a process that allows the
      implementation of the mentioned dual-labeling system to anoxic milieus, the
      aerobic fluorescence recovery of mCherry and GFPmut3, as well as the effect of pH
      on their fluorescence intensities, was studied. The findings present a solution
      to an intrinsic problem that has long hampered the utilization of this system,
      highlight its pH limitations, and provide experimental tools that will help
      broaden its horizon of application to other fields.IMPORTANCE Many anaerobic
      environments, like the gastrointestinal tract, anaerobic digesters, and the
      interiors of dense biofilms, have been shown to be hotspots for horizontal gene
      transfer (HGT). Despite the increasing wealth of reports warning about the
      alarming spread of antibiotic resistance determinants, to date, HGT studies
      mainly rely on cultivation-based methods. Unfortunately, the relevance of these
      studies is often questionable, as only a minor fraction of bacteria can be
      cultivated. A recently developed approach to monitoring the fate of plasmids in
      microbial communities is based on a fluorescence dual-labeling system and allows
      the bypassing of cultivation. However, the fluorescent proteins on which it is
      founded are constrained by pH levels and by their strict dependence on oxygen for
      the maturation of their fluorophores. This study focused on the development and
      validation of an appropriate aerobic fluorescence recovery (AFR) method for this
      platform, as this embodies the missing technical link impeding its implementation
      in anoxic environments.

PMID- 29330183
TI  - Campylobacter jejuni Colonization in the Crow Gut Involves Many Deletions within
      the Cytolethal Distending Toxin Gene Cluster.
AB  - Campylobacter spp. are major causes of gastroenteritis worldwide. The virulence
      potential of Campylobacter shed in crow feces obtained from a roost area in
      Bothell, Washington, was studied and compared with that from isolates from other
      parts of Washington and from a different crow species 7,000 miles away in
      Kolkata, India. Campylobacter organisms were isolated from 61% and 69% of the
      fecal samples obtained from Washington and Kolkata, respectively, and were
      confirmed to be C. jejuni The cytolethal distending toxin (CDT) gene cluster from
      these isolates revealed a truncated sequence of approximately 1,350 bp.
      Sequencing of the gene cluster revealed two types of mutations: a 668-bp deletion
      across cdtA and cdtB and a 51-bp deletion within cdtB Some strains had additional
      20-bp deletions in cdtB In either case, a functional toxin is not expected; a
      functional toxin is produced by the expression of three tandem genes, cdtA, cdtB,
      and cdtC Reverse transcriptase PCR with total RNA extracted from the isolates
      showed no expression of cdtB A toxin assay performed with these isolates on HeLa
      cells failed to show cytotoxic effects on the cells. However, the isolates were
      able to colonize the chicken ceca for a period of at least 4 weeks, similar to
      that of a clinical isolate. Other virulence gene markers, flagellin A and CadF,
      were present in 100% of the isolates. Our study suggests that crows carry the
      bacterium C. jejuni but with a dysfunctional toxin protein that is expected to
      drastically reduce its potential to cause diarrhea.IMPORTANCE Campylobacters are
      a major cause of gastroenteritis in humans. Since outbreaks have most often been
      correlated with poultry or unpasteurized dairy products, contact with farm
      animals, or contaminated water, historically, the majority of the studies have
      been with campylobacter isolates from poultry, domestic animals, and human
      patients. However, the bacterium has a broad host range that includes birds.
      These reservoirs need to be investigated, because the identification of the
      source and a determination of the transmission routes for a pathogen are
      important for the development of evidence-based disease control programs. In this
      study, two species of the human-commensal crow, from two different geographical
      regions separated by 7,000 miles of land and water, have been examined for their
      ability to cause disease by shedding campylobacters. Our results show that the
      crow may not play a significant role in campylobacteriosis, because the
      campylobacter organisms they shed produce a nonfunctional toxin.

PMID- 29330184
TI  - Microbiomes in Dishwashers: Analysis of the microbial diversity and putative
      opportunistic pathogens in dishwasher biofilm communities.
AB  - Extreme habitats are not only limited to natural environments, but also apply to
      man-made systems, for instance household appliances such as dishwashers. Limiting
      factors, such as high temperatures, high and low pH, high NaCl concentrations,
      presence of detergents and shear force from water during washing cycles define
      the microbial survival in this extreme system. Fungal and bacterial diversity in
      biofilms isolated from rubber seals of 24 different household dishwashers were
      investigated using next generation sequencing. Bacterial genera such as
      Pseudomonas, Escherichia and Acinetobacter, known to include opportunistic
      pathogens, were represented in most samples. The most frequently encountered
      fungal genera in these samples belonged to Candida, Cryptococcus and Rhodotorula,
      also known to include opportunistic pathogenic representatives. This study showed
      how specific conditions of the dishwashers impact the abundance of microbial
      groups, and investigated on the inter- and intra-kingdom interactions that shape
      these biofilms. The age, the usage frequency and hardness of incoming tap water
      of dishwashers had significant impact on bacterial and fungal composition.
      Representatives of Candida spp. were found at highest prevalence (100%) in all
      dishwashers and are assumingly one of the first colonizers in recent dishwashers.
      Pairwise correlations in tested microbiome showed that certain bacterial groups
      co-occur and so did the fungal groups. In mixed bacterial-fungal biofilms, early
      adhesion, contact and interactions were vital in the process of biofilm
      formation, where mixed complexes of the two, bacteria and fungi, could provide a
      preliminary biogenic structure for the establishment of these biofilms.IMPORTANCE
      Worldwide demand for household appliances, such as dishwashers and washing
      machines, is increasing, as well as the number of immune-compromised individuals.
      The harsh conditions in household dishwashers should prevent growth of most
      microorganisms. However, our research shows that persisting poly-extremotolerant
      groups of microorganisms in household appliances are well established under these
      unfavourable conditions, supported by the biofilm mode of growth. The
      significance of our research is in identifying the microbial composition of
      biofilms formed on dishwasher rubber seals, how diverse abiotic conditions
      affects microbiota and which key members were represented in early colonisation
      and contamination of dishwashers, as these appliances can present a source of
      domestic cross-contamination leading to broader medical impacts.

PMID- 29330185
TI  - MgtE Homolog FicI Acts as a Secondary Ferrous Iron Importer in Shewanella
      oneidensis Strain MR-1.
AB  - The transport of metals into and out of cells is necessary for the maintenance of
      appropriate intracellular concentrations. Metals are needed for incorporation
      into metalloproteins but become toxic at higher concentrations. Many metal
      transport proteins have been discovered in bacteria, including the Mg2+
      transporter E (MgtE) family of passive Mg2+/Co2+ cation-selective channels. Low
      sequence identity exists between members of the MgtE family, indicating that
      substrate specificity may differ among MgtE transporters. Under anoxic
      conditions, dissimilatory metal-reducing bacteria, such as Shewanella and
      Geobacter species, are exposed to high levels of soluble metals, including Fe2+
      and Mn2+ Here we characterize SO_3966, which encodes an MgtE homolog in
      Shewanella oneidensis that we name FicI (ferrous iron and cobalt importer) based
      on its role in maintaining metal homeostasis. A SO_3966 deletion mutant exhibits
      enhanced growth over that of the wild type under conditions with high Fe2+ or
      Co2+ concentrations but exhibits wild-type Mg2+ transport and retention
      phenotypes. Conversely, deletion of feoB, which encodes an energy-dependent Fe2+
      importer, causes a growth defect under conditions of low Fe2+ concentrations but
      not high Fe2+ concentrations. We propose that FicI represents a secondary, less
      energy-dependent mechanism for iron uptake by S. oneidensis under high Fe2+
      concentrations.IMPORTANCEShewanella oneidensis MR-1 is a target of microbial
      engineering for potential uses in biotechnology and the bioremediation of heavy
      metal-contaminated environments. A full understanding of the ways in which S.
      oneidensis interacts with metals, including the means by which it transports
      metal ions, is important for optimal genetic engineering of this and other
      organisms for biotechnology purposes such as biosorption. The MgtE family of
      metal importers has been described previously as Mg2+ and Co2+ transporters. This
      work broadens that designation with the discovery of an MgtE homolog in S.
      oneidensis that imports Fe2+ but not Mg2+ The research presented here also
      expands our knowledge of the means by which microorganisms have adapted to take
      up essential nutrients such as iron under various conditions.

PMID- 29330186
TI  - Effect of Plasmid Design and Type of Integration Event on Recombinant Protein
      Expression in Pichia pastoris.
AB  - Pichia pastoris (syn. Komagataella phaffii) is one of the most common eukaryotic
      expression systems for heterologous protein production. Expression cassettes are
      typically integrated in the genome to obtain stable expression strains. In
      contrast to Saccharomyces cerevisiae, where short overhangs are sufficient to
      target highly specific integration, long overhangs are more efficient in P.
      pastoris and ectopic integration of foreign DNA can occur. Here, we aimed to
      elucidate the influence of ectopic integration by high-throughput screening of
      >700 transformants and whole-genome sequencing of 27 transformants. Different
      vector designs and linearization approaches were used to mimic the most common
      integration events targeted in P. pastoris Fluorescence of an enhanced green
      fluorescent protein (eGFP) reporter protein was highly uniform among
      transformants when the expression cassettes were correctly integrated in the
      targeted locus. Surprisingly, most nonspecifically integrated transformants
      showed highly uniform expression that was comparable to specific integration,
      suggesting that nonspecific integration does not necessarily influence
      expression. However, a few clones (<10%) harboring ectopically integrated
      cassettes showed a greater variation spanning a 25-fold range, surpassing
      specifically integrated reference strains up to 6-fold. High-expression strains
      showed a correlation between increased gene copy numbers and high reporter
      protein fluorescence levels. Our results suggest that for comparing expression
      levels between strains, the integration locus can be neglected as long as a
      sufficient numbers of transformed strains are compared. For expression
      optimization of highly expressible proteins, increasing copy number appears to be
      the dominant positive influence rather than the integration locus, genomic
      rearrangements, deletions, or single-nucleotide polymorphisms (SNPs).IMPORTANCE
      Yeasts are commonly used as biotechnological production hosts for proteins and
      metabolites. In the yeast Saccharomyces cerevisiae, expression cassettes carrying
      foreign genes integrate highly specifically at the targeted sites in the genome.
      In contrast, cassettes often integrate at random genomic positions in
      nonconventional yeasts, such as Pichia pastoris (syn. Komagataella phaffii).
      Hence, cells from the same transformation event often behave differently, with
      significant clonal variation necessitating the screening of large numbers of
      strains. The importance of this study is that we systematically investigated the
      influence of integration events in more than 700 strains. Our findings provide
      novel insight into clonal variation in P. pastoris and, thus, how to avoid
      pitfalls and obtain reliable results. The underlying mechanisms may also play a
      role in other yeasts and hence could be generally relevant for recombinant yeast
      protein production strains.

PMID- 29330187
TI  - Acquisition of a Novel Sulfur-Oxidizing Symbiont in the Gutless Marine Worm
      Inanidrilus exumae.
AB  - Gutless phallodrilines are marine annelid worms without a mouth or gut, which
      live in an obligate association with multiple bacterial endosymbionts that supply
      them with nutrition. In this study, we discovered an unusual symbiont community
      in the gutless phallodriline Inanidrilus exumae that differs markedly from the
      microbiomes of all 22 of the other host species examined. Comparative 16S rRNA
      gene sequence analysis and fluorescence in situ hybridization revealed that I.
      exumae harbors cooccurring gamma-, alpha-, and deltaproteobacterial symbionts,
      while all other known host species harbor gamma- and either alpha- or
      deltaproteobacterial symbionts. Surprisingly, the primary chemoautotrophic sulfur
      oxidizer "Candidatus Thiosymbion" that occurs in all other gutless phallodriline
      hosts does not appear to be present in I. exumae Instead, I. exumae harbors a
      bacterial endosymbiont that resembles "Ca Thiosymbion" morphologically and
      metabolically but originates from a novel lineage within the class
      Gammaproteobacteria This endosymbiont, named Gamma 4 symbiont here, had a 16S
      rRNA gene sequence that differed by at least 7% from those of other free-living
      and symbiotic bacteria and by 10% from that of "Ca Thiosymbion." Sulfur globules
      in the Gamma 4 symbiont cells, as well as the presence of genes characteristic
      for autotrophy (cbbL) and sulfur oxidation (aprA), indicate that this symbiont is
      a chemoautotrophic sulfur oxidizer. Our results suggest that a novel lineage of
      free-living bacteria was able to establish a stable and specific association with
      I. exumae and appears to have displaced the "Ca Thiosymbion" symbionts originally
      associated with these hosts.IMPORTANCE All 22 gutless marine phallodriline
      species examined to date live in a highly specific association with
      endosymbiotic, chemoautotrophic sulfur oxidizers called "Ca Thiosymbion." These
      symbionts evolved from a single common ancestor and represent the ancestral trait
      for this host group. They are transmitted vertically and assumed to be in
      transition to becoming obligate endosymbionts. It is therefore surprising that
      despite this ancient, evolutionary relationship between phallodriline hosts and
      "Ca Thiosymbion," these symbionts are apparently no longer present in Inanidrilus
      exumae They appear to have been displaced by a novel lineage of sulfur-oxidizing
      bacteria only very distantly related to "Ca Thiosymbion." Thus, this study
      highlights the remarkable plasticity of both animals and bacteria in establishing
      beneficial associations: the phallodriline hosts were able to acquire and
      maintain symbionts from two very different lineages of bacteria, while sulfur
      oxidizing bacteria from two very distantly related lineages were able to
      independently establish symbiotic relationships with phallodriline hosts.

PMID- 29330188
TI  - Germination, Outgrowth, and Vegetative-Growth Kinetics of Dry-Heat-Treated
      Individual Spores of Bacillus Species.
AB  - DNA damage kills dry-heated spores of Bacillus subtilis, but dry-heat-treatment
      effects on spore germination and outgrowth have not been studied. This is
      important, since if dry-heat-killed spores germinate and undergo outgrowth, toxic
      proteins could be synthesized. Here, Raman spectroscopy and differential
      interference contrast microscopy were used to study germination and outgrowth of
      individual dry-heat-treated B. subtilis and Bacillus megaterium spores. The major
      findings in this work were as follows: (i) spores dry-heat-treated at 140 degrees
      C for 20 min lost nearly all viability but retained their Ca2+-dipicolinic acid
      (CaDPA) depot; (ii) in most cases, dry-heat treatment increased the average times
      and variability of all major germination events in B. subtilis spore germination
      with nutrient germinants or CaDPA, and in one nutrient germination event with B.
      megaterium spores; (iii) B. subtilis spore germination with dodecylamine, which
      activates the spore CaDPA release channel, was unaffected by dry-heat treatment;
      (iv) these results indicate that dry-heat treatment likely damages spore proteins
      important in nutrient germinant recognition and cortex peptidoglycan hydrolysis,
      but not CaDPA release itself; and (v) analysis of single spores incubated on
      nutrient-rich agar showed that while dry-heat-treated spores that are dead can
      complete germination, they cannot proceed into outgrowth and thus not to
      vegetative growth. The results of this study provide new information on the
      effects of dry heat on bacterial spores and indicate that dry-heat sterilization
      regimens should produce spores that cannot outgrow and thus cannot synthesize
      potentially dangerous proteins.IMPORTANCE Much research has shown that high
      temperature dry heat is a promising means for the inactivation of spores on
      medical devices and spacecraft decontamination. Dry heat is known to kill
      Bacillus subtilis spores by DNA damage. However, knowledge about the effects of
      dry-heat treatment on spore germination and outgrowth is limited, especially at
      the single spore level. In the current work, Raman spectroscopy and differential
      interference contrast microscopy were used to analyze CaDPA levels in and
      kinetics of nutrient- and non-nutrient germination of multiple individual dry
      heat-treated B. subtilis and Bacillus megaterium spores that were largely dead.
      The outgrowth and subsequent cell division of these germinated but dead dry-heat
      treated spores were also examined. The knowledge obtained in this study will help
      understand the effects of dry heat on spores both on Earth and in space, and
      indicates that dry heat can be safely used for sterilization purposes.

PMID- 29330189
TI  - Targeted Synthesis and Characterization of a Gene Cluster Encoding NAD(P)H
      Dependent 3alpha-, 3beta-, and 12alpha-Hydroxysteroid Dehydrogenases from
      Eggerthella CAG:298, a Gut Metagenomic Sequence.
AB  - Gut metagenomic sequences provide a rich source of microbial genes, the majority
      of which are annotated by homology or unknown. Genes and gene pathways that
      encode enzymes catalyzing biotransformation of host bile acids are important to
      identify in gut metagenomic sequences due to the importance of bile acids in gut
      microbiome structure and host physiology. Hydroxysteroid dehydrogenases (HSDHs)
      are pyridine nucleotide-dependent enzymes with stereospecificity and
      regiospecificity for bile acid and steroid hydroxyl groups. HSDHs have been
      identified in several protein families, including medium-chain and short-chain
      dehydrogenase/reductase families as well as the aldo-keto reductase family. These
      protein families are large and contain diverse functionalities, making prediction
      of HSDH-encoding genes difficult and necessitating biochemical characterization.
      We located a gene cluster in Eggerthella sp. CAG:298 predicted to encode three
      HSDHs (CDD59473, CDD59474, and CDD59475) and synthesized the genes for
      heterologous expression in Escherichia coli We then screened bile acid substrates
      against the purified recombinant enzymes. CDD59475 is a novel 12alpha-HSDH, and
      we determined that CDD59474 (3alpha-HSDH) and CDD59473 (3beta-HSDH) constitute
      novel enzymes in an iso-bile acid pathway. Phylogenetic analysis of these HSDHs
      with other gut bacterial HSDHs and closest homologues in the database revealed
      predictable clustering of HSDHs by function and identified several likely HSDH
      sequences from bacteria isolated or sequenced from diverse mammalian and avian
      gut samples.IMPORTANCE Bacterial HSDHs have the potential to significantly alter
      the physicochemical properties of bile acids, with implications for
      increased/decreased toxicity for gut bacteria and the host. The generation of oxo
      bile acids is known to inhibit host enzymes involved in glucocorticoid metabolism
      and may alter signaling through nuclear receptors such as farnesoid X receptor
      and G-protein-coupled receptor TGR5. Biochemical or similar approaches are
      required to fill in many gaps in our ability to link a particular enzymatic
      function with a nucleic acid or amino acid sequence. In this regard, we have
      identified a novel 12alpha-HSDH and a novel set of genes encoding an iso-bile
      acid pathway (3alpha-HSDH and 3beta-HSDH) involved in epimerization and
      detoxification of harmful secondary bile acids.

PMID- 29330190
TI  - Influence of pig farming on the human's nasal microbiota: The key role of the
      airborne microbial communities.
AB  - It has been hypothesized that the environment can influence the composition of
      the nasal microbiota. However, the direct influence of pig farming on the
      anterior and posterior nasal microbiota is unknown. Using a cross-sectional
      design, pig farms (n=28) were visited in 2014-2015 and nasal swabs from 43 pig
      farmers and 56 pigs as well as 27 air samples taken in the vicinity of pig
      enclosure were collected. As controls, nasal swabs from 17 cow farmers and 26 non
      animal exposed individuals were also included. Analyses of the microbiota were
      performed based on 16S rRNA amplicon sequencing and the DADA2 pipeline to define
      sequence variants (SVs). We found that pig farming is strongly associated with
      specific microbial signatures (including alpha- and beta-diversity), which are
      reflected in the microbiota of the human nose. Furthermore, the microbial
      communities were more similar within the same farm as compared to between the
      different farms, indicating a specific microbiota pattern for each pig farm. In
      total, there were 82 SVs that occurred significantly more abundantly in samples
      from pig farms than from cow farmers and non-exposed (i.e. the core pig farm
      microbiota). Of those, nine SVs were significantly associated with the posterior
      part of the humans' nose. The results strongly indicate that pig farming is
      associated with a distinct human nose microbiota. Finally, the community
      structures derived by the DADA2 pipeline showed an excellent agreement with the
      outputs of the mothur pipeline which was revealed by procrustes
      analyses.Importance The knowledge about the influence of animal keeping on the
      human microbiome is important. Previous research shows that pets are
      significantly affecting the microbial communities of humans. However, the effect
      of animal farming on the human microbiome is less clear although it is known that
      the air in farms, and in particular pig farms, is charged with high amounts of
      dust, bacteria and fungi. In this study we have simultaneously investigated the
      nasal microbiota of pigs, humans and the environment in pig farms. We reveal an
      enormous impact of pig farming on the human nasal microbiota which is far more
      pronounced as compared to cow farming. In addition, we have analyzed the airborne
      microbiota and found significant associations suggesting an animal-human
      transmission of the microbiota within pig farms. We also reveal that microbial
      patterns are farm-specific suggesting that the environment influences animals and
      humans in a similar manner.

PMID- 29330192
TI  - NHS data show A&E patients waiting longer and big rise in GP flu consultations.

PMID- 29330191
TI  - Thermophilic Alkaline Fermentation Followed by Mesophilic Anaerobic Digestion for
      Efficient Hydrogen and Methane Production from Waste-Activated Sludge: Dynamics
      of Bacterial Pathogens as Revealed by the Combination of Metagenomic and
      Quantitative PCR Analyses.
AB  - Thermophilic alkaline fermentation followed by mesophilic anaerobic digestion
      (TM) for hydrogen and methane production from waste-activated sludge (WAS) was
      investigated. The TM process was also compared to a process with mesophilic
      alkaline fermentation followed by a mesophilic anaerobic digestion (MM) and one
      stage mesophilic anaerobic digestion (M) process. The results showed that both
      hydrogen yield (74.5 ml H2/g volatile solids [VS]) and methane yield (150.7 ml
      CH4/g VS) in the TM process were higher than those (6.7 ml H2/g VS and 127.8 ml
      CH4/g VS, respectively) in the MM process. The lowest methane yield (101.2 ml
      CH4/g VS) was obtained with the M process. Taxonomic results obtained from
      metagenomic analysis showed that different microbial community compositions were
      established in the hydrogen reactors of the TM and MM processes, which also
      significantly changed the microbial community compositions in the following
      methane reactors compared to that with the M process. The dynamics of bacterial
      pathogens were also evaluated. For the TM process, the reduced diversity and
      total abundance of bacterial pathogens in WAS were observed in the hydrogen
      reactor and were further reduced in the methane reactor, as revealed by
      metagenomic analysis. The results also showed not all bacterial pathogens were
      reduced in the reactors. For example, Collinsella aerofaciens was enriched in the
      hydrogen reactor, which was also confirmed by quantitative PCR (qPCR) analysis.
      The study further showed that qPCR was more sensitive for detecting bacterial
      pathogens than metagenomic analysis. Although there were some differences in the
      relative abundances of bacterial pathogens calculated by metagenomic and qPCR
      approaches, both approaches demonstrated that the TM process was more efficient
      for the removal of bacterial pathogens than the MM and M processes.IMPORTANCE
      This study developed an efficient process for bioenergy (H2 and CH4) production
      from WAS and elucidates the dynamics of bacterial pathogens in the process, which
      is important for the utilization and safe application of WAS. The study also made
      an attempt to combine metagenomic and qPCR analyses to reveal the dynamics of
      bacterial pathogens in anaerobic processes, which could overcome the limitations
      of each method and provide new insights regarding bacterial pathogens in
      environmental samples.

PMID- 29330193
TI  - Structure of the human myostatin precursor and determinants of growth factor
      latency.
AB  - Myostatin, a key regulator of muscle mass in vertebrates, is biosynthesised as a
      latent precursor in muscle and is activated by sequential proteolysis of the pro
      domain. To investigate the molecular mechanism by which pro-myostatin remains
      latent, we have determined the structure of unprocessed pro-myostatin and
      analysed the properties of the protein in its different forms. Crystal structures
      and SAXS analyses show that pro-myostatin adopts an open, V-shaped structure with
      a domain-swapped arrangement. The pro-mature complex, after cleavage of the furin
      site, has significantly reduced activity compared with the mature growth factor
      and persists as a stable complex that is resistant to the natural antagonist
      follistatin. The latency appears to be conferred by a number of distinct features
      that collectively stabilise the interaction of the pro-domains with the mature
      growth factor, enabling a regulated stepwise activation process, distinct from
      the prototypical pro-TGF-beta1. These results provide a basis for understanding
      the effect of missense mutations in pro-myostatin and pave the way for the design
      of novel myostatin inhibitors.

PMID- 29330194
TI  - Telotristat ethyl in carcinoid syndrome: safety and efficacy in the TELECAST
      phase 3 trial.
AB  - Telotristat ethyl, a tryptophan hydroxylase inhibitor, was efficacious and well
      tolerated in the phase 3 TELESTAR study in patients with carcinoid syndrome (CS)
      experiencing >=4 bowel movements per day (BMs/day) while on somatostatin analogs
      (SSAs). TELECAST, a phase 3 companion study, assessed the safety and efficacy of
      telotristat ethyl in patients with CS (diarrhea, flushing, abdominal pain, nausea
      or elevated urinary 5-hydroxyindoleacetic acid (u5-HIAA)) with <4 BMs/day on SSAs
      (or >=1 symptom or >=4 BMs/day if not on SSAs) during a 12-week double-blind
      treatment period followed by a 36-week open-label extension (OLE). The primary
      safety and efficacy endpoints were incidence of treatment-emergent adverse events
      (TEAEs) and percent change from baseline in 24-h u5-HIAA at week 12. Patients (N
      = 76) were randomly assigned (1:1:1) to receive placebo or telotristat ethyl 250
      mg or 500 mg 3 times per day (tid); 67 continued receiving telotristat ethyl 500
      mg tid during the OLE. Through week 12, TEAEs were generally mild to moderate in
      severity; 5 (placebo), 1 (telotristat ethyl 250 mg) and 3 (telotristat ethyl 500
      mg) patients experienced serious events, and the rate of TEAEs in the OLE was
      comparable. At week 12, significant reductions in u5-HIAA from baseline were
      observed, with Hodges-Lehmann estimators of median treatment differences from
      placebo of -54.0% (95% confidence limits, -85.0%, -25.1%, P < 0.001) and -89.7%
      (95% confidence limits, -113.1%, -63.9%, P < 0.001) for telotristat ethyl 250 mg
      and 500 mg. These results support the safety and efficacy of telotristat ethyl
      when added to SSAs in patients with CS diarrhea (ClinicalTrials.gov identifier:
      Nbib2063659).

PMID- 29330195
TI  - DICER1 gene mutations in endocrine tumors.
AB  - In this review, the importance of the DICER1 gene in the function of endocrine
      cells is discussed. There is conclusive evidence that DICER1 mutations play a
      crucial role in the development, progression, cell proliferation, therapeutic
      responsiveness and behavior of several endocrine tumors. We review the literature
      of DICER1 gene mutations in thyroid, parathyroid, pituitary, pineal gland,
      endocrine pancreas, paragangliomas, medullary, adrenocortical, ovarian and
      testicular tumors. Although significant progress has been made during the last
      few years, much more work is needed to fully understand the significance of
      DICER1 mutations.

PMID- 29330197
TI  - Diplomatic impasse prevents cardiologists from attending conference in Qatar.

PMID- 29330196
TI  - Higher prevalence of lymph node metastasis in prostate cancer in patients with
      diabetes.

PMID- 29330198
TI  - Systematic review of drowning in India: assessment of burden and risk.
AB  - AIM: To examine the burden and risk factors for fatal and non-fatal drowning in
      India. METHODS: Relevant literature was identified through a systematic search of
      19 electronic databases and 19 national and global, institutional, organisational
      and government sources of injury data. Search terms used pertained to drowning,
      injury, trauma, morbidity and mortality in India. RESULTS: A total of 16 research
      articles and five data sources were included in the review. Three national data
      sources provided counts of drowning deaths, reporting a range of 1348-62 569
      drowning deaths per year. A further three national data sources provided
      information on drowning-related morbidity; however, each source presented
      different outcome measures making comparison difficult. Ten research studies
      investigated risk factors associated with drowning in India. Key risk factors
      reported were male gender, young age (0-5 years) and individuals residing in the
      North-Eastern part of the country who have high exposure to water sources within
      community settings. CONCLUSION: Drowning-related morbidity and mortality have a
      significant impact on India, with risk factors identified for this setting
      similar to those within other low-income and middle-income countries. Regional
      data which look beyond routinely collected data are required to accurately
      investigate the burden and impact of drowning, to inform targeted, context
      specific approaches for drowning reduction initiatives.

PMID- 29330199
TI  - Association between community socioeconomic characteristics and access to youth
      flag football.
AB  - BACKGROUND: The American Academy of Pediatrics has recommended that opportunities
      for non-tackling American football (e.g., flag football) be expanded, given
      concerns about the risks of brain trauma from tackle football. This study tested
      the hypothesis that flag football would be more accessible in communities
      characterised by higher socioeconomic status residents. METHODS: In July 2017,
      the locations of community-based organisations offering youth flag and tackle
      football for youth between the ages of 6 and 13 in two US states (Georgia and
      Washington) were aggregated (n=440). Organisations were coded in terms of the
      availability of tackle and/or flag football teams for youth at each year of age
      between 6 and 13. Multivariate logistic regression analyses were used to assess
      the odds of a community-based football organisation offering flag football, by
      community socioeconomic and demographic characteristics. RESULTS: In both states,
      communities with more educated residents were more likely to offer flag football
      for youth aged 6-12. For example, among 6 year-olds every 10% increase in the
      number of adult residents with a college education was associated with 1.51 times
      the odds of flag football availability (95% CI 1.22 to 1.86, P<0.001).
      CONCLUSION: These results suggest that youth living in communities characterised
      by low educational attainment are less likely than other youth to have the option
      of a lower contact alternative to tackle football. Relying on voluntary community
      level adoption of lower contact alternatives to tackle football may result in
      inequitable access to such sport options. This may contribute to an inequitable
      burden of brain trauma from youth sport.

PMID- 29330201
TI  - CORRECTION.

PMID- 29330200
TI  - PWWP-DOMAIN INTERACTOR OF POLYCOMBS1 Interacts with Polycomb-Group Proteins and
      Histones and Regulates Arabidopsis Flowering and Development.
AB  - Polycomb-group (PcG) proteins mediate epigenetic gene regulation by setting
      H3K27me3 via Polycomb Repressive Complex 2 (PRC2). In plants, it is largely
      unclear how PcG proteins are recruited to their target genes. Here, we identified
      the PWWP-DOMAIN INTERACTOR OF POLYCOMBS1 (PWO1) protein, which interacts with all
      three Arabidopsis thaliana PRC2 histone methyltransferases and is required for
      maintaining full H3 occupancy at several Arabidopsis genes. PWO1 localizes and
      recruits CURLY LEAF to nuclear speckles in Nicotiana benthamiana nuclei,
      suggesting a role in spatial organization of PcG regulation. PWO1 belongs to a
      gene family with three members having overlapping activities: pwo1 pwo2 pwo3
      triple mutants are seedling lethal and show shoot and root meristem arrest, while
      pwo1 single mutants are early flowering. Interestingly, the PWWP domain of PWO1
      confers binding to histones, which is reduced by a point mutation in a highly
      conserved residue of this domain and blocked by phosphorylation of H3S28. PWO1
      carrying this mutation is not able to fully complement the pwo1 pwo2 pwo3 triple
      mutant, indicating the requirement of this domain for PWO1 in vivo activity.
      Thus, the PWO family may present a novel class of histone readers that are
      involved in recruiting PcG proteins to subnuclear domains and in promoting
      Arabidopsis development.

PMID- 29330202
TI  - High-Risk TP53 Mutations Are Associated with Extranodal Extension in Oral Cavity
      Squamous Cell Carcinoma.
AB  - Purpose: Development of extranodal extension (ENE) has been associated with poor
      survival in patients with oral cavity squamous cell carcinoma (OSCC). Here, we
      sought to confirm the role of ENE as a poor prognostic factor, and identify
      genomic and epigenetic markers of ENE in order to develop a predictive model and
      improve treatment selection.Experimental Design: An institutional cohort (The
      University of Texas MD Anderson Cancer Center) was utilized to confirm the impact
      of ENE on clinical outcomes and evaluate the genomic signature of primary and ENE
      containing tissue. OSCC data from The Cancer Genome Atlas (TCGA) were analyzed
      for the presence of molecular events associated with nodal and ENE
      status.Results: ENE was associated with decreased overall and disease-free
      survival. Mutation of the TP53 gene was the most common event in ENE+ OSCC. The
      frequency of TP53 mutation in ENE+ tumors was higher compared with ENE- tumors
      and wild-type (WT) TP53 was highly represented in pN0 tumors. pN+ENE+ patients
      had the highest proportion of high-risk TP53 mutations. Both primary tumors (PT)
      and lymph nodes with ENE (LN) exhibited a high rate of TP53 mutations (58.8% and
      58.8%, respectively) with no significant change in allele frequency between the
      two tissue sites.Conclusions: ENE is one of the most significant markers of OSCC
      OS and DFS. There is a shift toward a more aggressive biological phenotype
      associated with high-risk mutations of the TP53 gene. Prospective clinical trials
      are required to determine whether TP53 mutational status can be used for
      personalized treatment decisions. Clin Cancer Res; 24(7); 1727-33. (c)2018 AACR.

PMID- 29330203
TI  - Personalized RNA Medicine for Pancreatic Cancer.
AB  - Purpose: Since drug responses vary between patients, it is crucial to develop pre
      clinical or co-clinical strategies that forecast patient response. In this study,
      we tested whether RNA-based therapeutics were suitable for personalized medicine
      by using patient-derived-organoid (PDO) and patient-derived-xenograft (PDX)
      models.Experimental Design: We performed microRNA (miRNA) profiling of PDX
      samples to determine the status of miRNA deregulation in individual pancreatic
      ductal adenocarcinoma (PDAC) patients. To deliver personalized RNA-based-therapy
      targeting oncogenic miRNAs that form part of this common PDAC miRNA over
      expression signature, we packaged antimiR oligonucleotides against one of these
      miRNAs in tumor-penetrating nanocomplexes (TPN) targeting cell surface proteins
      on PDAC tumors.Results: As a validation for our pre-clinical strategy, the
      therapeutic potential of one of our nano-drugs, TPN-21, was first shown to
      decrease tumor cell growth and survival in PDO avatars for individual patients,
      then in their PDX avatars.Conclusions: This general approach appears suitable for
      co-clinical validation of personalized RNA medicine and paves the way to
      prospectively identify patients with eligible miRNA profiles for personalized RNA
      based therapy. Clin Cancer Res; 24(7); 1734-47. (c)2018 AACR.

PMID- 29330204
TI  - Pazopanib Exposure Relationship with Clinical Efficacy and Safety in the Adjuvant
      Treatment of Advanced Renal Cell Carcinoma.
AB  - Purpose: PROTECT, a phase III, randomized, placebo-controlled study, evaluated
      pazopanib efficacy and safety in the adjuvant renal cell carcinoma setting. The
      relationship between pazopanib exposure (Ctrough) and efficacy and safety was
      evaluated.Patients and Methods: Evaluable steady-state blood trough
      concentrations were collected from 311 patients at week 3 or 5 (early Ctrough)
      and 250 patients at week 16 or 20 (late Ctrough). Pazopanib pharmacokinetic (PK)
      data were analyzed via a population model approach. Relationship between Ctrough
      or dose intensity and disease-free survival (DFS) was explored via Kaplan-Meier
      and multivariate analysis. Adverse events (AE) and AE-related treatment
      discontinuation proportions were summarized by Ctrough quartiles.Results: Most
      (>90%) patients with early or late Ctrough data started on 600 mg. Mean early and
      late Ctrough overlapped across dose levels. Patients with higher early Ctrough
      quartiles achieved longer DFS (adjusted HR, 0.58; 95% confidence interval, 0.42
      0.82; P = 0.002). Patients achieving early or late Ctrough >20.5 MUg/mL had
      significantly longer DFS: not estimable (NE) versus 29.5 months, P = 0.006, and
      NE versus 29.9 months, P = 0.008, respectively. Dose intensity up to week 8 did
      not correlate with DFS, consistent with population PK model-based simulations
      showing overlapping pazopanib exposure with 600 and 800 mg doses. The proportion
      of AE-related treatment discontinuation and grade 3/4 AEs, with the exception of
      hypertension, was not correlated to CtroughConclusions: In the adjuvant setting,
      higher pazopanib Ctrough was associated with improved DFS and did not increase
      treatment discontinuations or grade 3/4 AEs, with the exception of hypertension.
      Clin Cancer Res; 24(13); 3005-13. (c)2018 AACRSee related commentary by Rini, p.
      2979.

PMID- 29330205
TI  - Clinical Utility of a STAT3-Regulated miRNA-200 Family Signature with Prognostic
      Potential in Early Gastric Cancer.
AB  - Purpose: The majority of gastric cancer patients are diagnosed with late-stage
      disease, for which distinct molecular subtypes have been identified that are
      potentially amenable to targeted therapies. However, there exists no molecular
      classification system with prognostic power for early-stage gastric cancer (EGC)
      because the molecular events promoting gastric cancer initiation remain ill
      defined.Experimental Design: miRNA microarrays were performed on gastric tissue
      from the gp130F/F preclinical EGC mouse model, prior to tumor initiation.
      Computation prediction algorithms were performed on multiple data sets and
      independent gastric cancer patient cohorts. Quantitative real-time PCR expression
      profiling was undertaken in gp130F/F-based mouse strains and human gastric cancer
      cells genetically engineered for suppressed activation of the oncogenic latent
      transcription factor STAT3. Human gastric cancer cells with modulated expression
      of the miR-200 family member miR-429 were also assessed for their proliferative
      response.Results: Increased expression of miR-200 family members is associated
      with both tumor initiation in a STAT3-dependent manner in gp130F/F mice and EGC
      (i.e., stage IA) in patient cohorts. Overexpression of miR-429 also elicited
      contrasting pro- and antiproliferative responses in human gastric cancer cells
      depending on their cellular histologic subtype. We also identified a miR-200
      family-regulated 15-gene signature that integrates multiple key current
      indicators of EGC, namely tumor invasion depth, differentiation, histology, and
      stage, and provides superior predictive power for overall survival compared with
      each EGC indicator alone.Conclusions: Collectively, our discovery of a STAT3
      regulated, miR-200 family-associated gene signature specific for EGC, with
      predictive power, provides a molecular rationale to classify and stratify EGC
      patients for endoscopic treatment. Clin Cancer Res; 24(6); 1459-72. (c)2018 AACR.

PMID- 29330206
TI  - Evolution of Cytogenetically Normal Acute Myeloid Leukemia During Therapy and
      Relapse: An Exome Sequencing Study of 50 Patients.
AB  - Purpose: To study mechanisms of therapy resistance and disease progression, we
      analyzed the evolution of cytogenetically normal acute myeloid leukemia (CN-AML)
      based on somatic alterations.Experimental Design: We performed exome sequencing
      of matched diagnosis, remission, and relapse samples from 50 CN-AML patients
      treated with intensive chemotherapy. Mutation patterns were correlated with
      clinical parameters.Results: Evolutionary patterns correlated with clinical
      outcome. Gain of mutations was associated with late relapse. Alterations of
      epigenetic regulators were frequently gained at relapse with recurring
      alterations of KDM6A constituting a mechanism of cytarabine resistance. Low KDM6A
      expression correlated with adverse clinical outcome, particularly in male
      patients. At complete remission, persistent mutations representing preleukemic
      lesions were observed in 48% of patients. The persistence of DNMT3A mutations
      correlated with shorter time to relapse.Conclusions: Chemotherapy resistance
      might be acquired through gain of mutations. Insights into the evolution during
      therapy and disease progression lay the foundation for tailored approaches to
      treat or prevent relapse of CN-AML. Clin Cancer Res; 24(7); 1716-26. (c)2018
      AACR.

PMID- 29330207
TI  - Early Assessment of Lung Cancer Immunotherapy Response via Circulating Tumor DNA.
AB  - Purpose: Decisions to continue or suspend therapy with immune checkpoint
      inhibitors are commonly guided by tumor dynamics seen on serial imaging. However,
      immunotherapy responses are uniquely challenging to interpret because tumors
      often shrink slowly or can appear transiently enlarged due to inflammation. We
      hypothesized that monitoring tumor cell death in real time by quantifying changes
      in circulating tumor DNA (ctDNA) levels could enable early assessment of
      immunotherapy efficacy.Experimental Design: We compared longitudinal changes in
      ctDNA levels with changes in radiographic tumor size and with survival outcomes
      in 28 patients with metastatic non-small cell lung cancer (NSCLC) receiving
      immune checkpoint inhibitor therapy. CtDNA was quantified by determining the
      allele fraction of cancer-associated somatic mutations in plasma using a
      multigene next-generation sequencing assay. We defined a ctDNA response as a >50%
      decrease in mutant allele fraction from baseline, with a second confirmatory
      measurement.Results: Strong agreement was observed between ctDNA response and
      radiographic response (Cohen's kappa, 0.753). Median time to initial response
      among patients who achieved responses in both categories was 24.5 days by ctDNA
      versus 72.5 days by imaging. Time on treatment was significantly longer for ctDNA
      responders versus nonresponders (median, 205.5 vs. 69 days; P < 0.001). A ctDNA
      response was associated with superior progression-free survival [hazard ratio
      (HR), 0.29; 95% CI, 0.09-0.89; P = 0.03], and superior overall survival (HR,
      0.17; 95% CI, 0.05-0.62; P = 0.007).Conclusions: A drop in ctDNA level is an
      early marker of therapeutic efficacy and predicts prolonged survival in patients
      treated with immune checkpoint inhibitors for NSCLC. Clin Cancer Res; 24(8); 1872
      80. (c)2018 AACR.

PMID- 29330209
TI  - Cognitive Computing to Guide Molecular-Based Therapy Selection: Steps Forward
      amid Abundant Need.

PMID- 29330208
TI  - Neuroendocrine Tumor Heterogeneity Adds Uncertainty to the World Health
      Organization 2010 Classification: Real-World Data from the Spanish Tumor Registry
      (R-GETNE).
AB  - BACKGROUND: Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are a
      complex family of tumors of widely variable clinical behavior. The World Health
      Organization (WHO) 2010 classification provided a valuable tool to stratify
      neuroendocrine neoplasms (NENs) in three prognostic subgroups based on the
      proliferation index. However, substantial heterogeneity remains within these
      subgroups, and simplicity sometimes entails an ambiguous and imprecise prognostic
      stratification. The purpose of our study was to evaluate the prognostic impact of
      histological differentiation within the WHO 2010 grade (G) 1/G2/G3 categories,
      and explore additional Ki-67 cutoff values in GEP-NENs. SUBJECTS, MATERIALS, AND
      METHODS: A total of 2,813 patients from the Spanish National Tumor Registry
      (RGETNE) were analyzed. Cases were classified by histological differentiation as
      NETs (neuroendocrine tumors [well differentiated]) or NECs (neuroendocrine
      carcinomas [poorly differentiated]), and by Ki-67 index as G1 (Ki-67 <2%), G2 (Ki
      67 3%-20%), or G3 (Ki-67 >20%). Patients were stratified into five cohorts: NET
      G1, NET-G2, NET-G3, NEC-G2, and NEC-G3. RESULTS: Five-year survival was 72%. Age,
      gender, tumor site, grade, differentiation, and stage were all independent
      prognostic factors for survival. Further subdivision of the WHO 2010 grading
      improved prognostic stratification, both within G2 (5-year survival: 81% [Ki-67
      3%-5%], 72% [Ki-67 6%-10%], 52% [Ki-67 11%-20%]) and G3 NENs (5-year survival:
      35% [Ki-67 21%-50%], 22% [Ki-67 51%-100%]). Five-year survival was significantly
      greater for NET-G2 versus NEC-G2 (75.5% vs. 58.2%) and NET-G3 versus NEC-G3
      (43.7% vs. 25.4%). CONCLUSION: Substantial clinical heterogeneity is observed
      within G2 and G3 GEP-NENs. The WHO 2010 classification can be improved by
      including the additive effect of histological differentiation and the
      proliferation index. IMPLICATIONS FOR PRACTICE: Gastroenteropancreatic
      neuroendocrine neoplasms are tumors of widely variable clinical behavior, roughly
      stratified by the World Health Organization (WHO) 2010 classification into three
      subgroups based on proliferation index. Real-world data from 2,813 patients of
      the Spanish Registry RGETNE demonstrated substantial clinical heterogeneity
      within grade (G) 2 and G3 neuroendocrine neoplasms. Tumor morphology and further
      subdivision of grading substantially improves prognostic stratification of these
      patients and may help individualize therapy. This combined, additive effect shall
      be considered in future classifications of neuroendocrine tumors and incorporated
      for stratification purposes in clinical trials.

PMID- 29330210
TI  - Trastuzumab Plus Pertuzumab Resistance Does Not Preclude Response to Lapatinib
      Plus Trastuzumab in HER2-Amplified Colorectal Cancer.
AB  - Human epidermal growth factor 2 (HER2) amplification represents a distinct
      molecular subgroup of colorectal cancers that is associated with anti-epidermal
      growth factor receptor resistance and sensitivity to dual HER2 targeting.
      Although clinical trials have reported activity for trastuzumab/pertuzumab and
      trastuzumab/lapatinib combinations, there are no reports on lapatinib plus
      trastuzumab activity after resistance to trastuzumab plus pertuzumab. Presented
      are three cases of HER2 amplified colorectal cancer that developed acquired
      refractoriness to trastuzumab pertuzumab with subsequent clinical benefit to
      lapatinib plus trastuzumab, highlighting the potential for HER2 tyrosine kinase
      inhibition plus trastuzumab in overcoming trastuzumab/pertuzumab resistance.

PMID- 29330211
TI  - Olanzapine-Based Triple Regimens Versus Neurokinin-1 Receptor Antagonist-Based
      Triple Regimens in Preventing Chemotherapy-Induced Nausea and Vomiting Associated
      with Highly Emetogenic Chemotherapy: A Network Meta-Analysis.
AB  - BACKGROUND: The current antiemetic prophylaxis for patients treated with highly
      emetogenic chemotherapy (HEC) included the olanzapine-based triplet and
      neurokinin-1 receptor antagonists (NK-1RAs)-based triplet. However, which one
      shows better antiemetic effect remained unclear. MATERIALS AND METHODS: We
      systematically reviewed 43 trials, involving 16,609 patients with HEC, which
      compared the following antiemetics at therapeutic dose range for the treatment of
      chemotherapy-induced nausea and vomiting: olanzapine, aprepitant, casopitant,
      fosaprepitant, netupitant, and rolapitant. The main outcomes were the proportion
      of patients who achieved no nausea, complete response (CR), and drug-related
      adverse events. A Bayesian network meta-analysis was performed. RESULTS:
      Olanzapine-based triple regimens showed significantly better no-nausea rate in
      overall phase and delayed phase than aprepitant-based triplet (odds ratios 3.18,
      3.00, respectively), casopitant-based triplet (3.78, 4.12, respectively),
      fosaprepitant-based triplet (3.08, 4.10, respectively), rolapitant-based triplet
      (3.45, 3.20, respectively), and conventional duplex regimens (4.66, 4.38,
      respectively). CRs of olanzapine-based triplet were roughly equal to different NK
      1RAs-based triplet but better than the conventional duplet. Moreover, no
      significant drug-related adverse events were observed in olanzapine-based triple
      regimens when compared with NK-1RAs-based triple regimens and duplex regimens.
      Additionally, the costs of olanzapine-based regimens were obviously much lower
      than the NK-1RA-based regimens. CONCLUSION: Olanzapine-based triplet stood out in
      terms of nausea control and drug price but represented no significant difference
      of CRs in comparison with NK-1RAs-based triplet. Olanzapine-based triple regimens
      should be an optional antiemetic choice for patients with HEC, especially those
      suffering from delayed phase nausea. IMPLICATIONS FOR PRACTICE: According to the
      results of this study, olanzapine-based triple antiemetic regimens were superior
      in both overall and delayed-phase nausea control when compared with various
      neurokinin-1 receptor antagonists-based triple regimens in patients with highly
      emetogenic chemotherapy (HEC). Olanzapine-based triplet was outstanding in terms
      of nausea control and drug price. For cancer patients with HEC, especially those
      suffering from delayed-phase nausea, olanzapine-based triple regimens should be
      an optional antiemetic choice.

PMID- 29330212
TI  - Early and Locally Advanced Metaplastic Breast Cancer: Presentation and Survival
      by Receptor Status in Surveillance, Epidemiology, and End Results (SEER) 2010
      2014.
AB  - BACKGROUND: Metaplastic breast cancer (MBC) is a rare disease subtype
      characterized by an aggressive clinical course. MBC is commonly triple negative
      (TN), although hormone receptor (HR) positive and human epidermal growth receptor
      2 (HER2) positive cases do occur. Previous studies have reported similar outcomes
      for MBC with regard to HR status. Less is known about outcomes for HER2 positive
      MBC. MATERIALS AND METHODS: Surveillance, Epidemiology, and End Results Program
      data were used to identify women diagnosed 2010-2014 with MBC or invasive ductal
      carcinoma (IDC). Kaplan-Meier curves estimated overall survival (OS) and
      multivariate Cox models were fitted. For survival analyses, only first cancers
      were included, and 2014 diagnoses were excluded to allow for sufficient follow
      up. RESULTS: Our MBC sample included 1,516 women. Relative to women with IDC,
      women with MBC were more likely to be older (63 vs. 61 years), black (16.0% vs.
      11.1%), and present with stage III disease (15.6% vs. 10.8%). HER2 positive and
      HER2 negative/HR positive MBC tumors represented 5.2% and 23.0% of cases. For MBC
      overall, 3-year OS was greatest for women with HER2 positive MBC (91.8%),
      relative to women with TN (75.4%) and HER2 negative/HR positive MBC (77.1%). This
      difference was more pronounced for stage III MBC, for which 3-year OS was 92.9%,
      47.1%, and 42.2% for women with HER2 positive, TN, and HER2 negative/HR positive
      MBC, respectively. A multivariate Cox model of MBC demonstrated that HER2
      positive tumors (relative to TN) were associated with improved survival (hazard
      ratio = 0.32, 95% confidence interval [CI] 0.13-0.79). In a second Cox model of
      exclusively HER2 positive tumors, OS did not differ between MBC and IDC disease
      subtypes (hazard ratio = 1.16, 95% CI 0.48-2.81). CONCLUSION: In this
      contemporary, population-based study of women with MBC, HER2 but not HR status
      was associated with improved survival. Survival was similar between HER2 positive
      MBC and HER2 positive IDC. This suggests HER2 positive MBC is responsive to HER2
      directed therapy, a finding that may offer insights for additional therapeutic
      approaches to MBC. IMPLICATIONS FOR PRACTICE: This population-based study reports
      recent outcomes, by receptor status, for women with metaplastic breast cancer.
      Survival in metaplastic breast cancer is not impacted by hormone receptor status.
      To the authors' knowledge, this is the first report indicating that women with
      human epidermal growth receptor 2 (HER2) positive metaplastic breast cancer have
      survival superior to women with HER2 negative metaplastic breast cancer and
      survival similar to women with HER2 positive invasive ductal carcinoma. This
      information can be used for counseling patients diagnosed with metaplastic breast
      cancer. Further understanding of HER2 positive metaplastic breast cancer could
      offer insights for the development of therapeutic approaches to metaplastic
      breast cancer more broadly.

PMID- 29330214
TI  - Association of Statin Dose With Amputation and Survival in Patients With
      Peripheral Artery Disease.
AB  - BACKGROUND: Statin dose guidelines for patients with peripheral artery disease
      (PAD) are largely based on coronary artery disease and stroke data. The aim of
      this study is to determine the effect of statin intensity on PAD outcomes of
      amputation and mortality. METHODS: Using an observational cohort study design and
      a validated algorithm, we identified patients with incident PAD (2003-2014) in
      the national Veterans Affairs data. Highest statin intensity exposure (high
      intensity versus low-to-moderate-intensity versus antiplatelet therapy but no
      statin use) was determined within 1 year of diagnosis of PAD. Outcomes of
      interest were lower extremity amputations and death. The association of statin
      intensity with incident amputation and mortality was assessed with Kaplan-Meier
      plots, Cox proportional hazards modeling, propensity score-matched analysis, and
      sensitivity and subgroup analyses, as well, to reduce confounding. RESULTS: In
      155 647 patients with incident PAD, more than a quarter (28%) were not on
      statins. Use of high-intensity statins was lowest in patients with PAD only
      (6.4%) in comparison with comorbid coronary/carotid disease (18.4%). Incident
      amputation and mortality risk declined significantly with any statin use in
      comparison with the antiplatelet therapy-only group. In adjusted Cox models, the
      high-intensity statin users were associated with lower amputation risk and
      mortality in comparison with antiplatelet therapy-only users (hazard ratio, 0.67;
      95% confidence interval, 0.61-0.74 and hazard ratio, 0.74; 95% confidence
      interval, 0.70-0.77, respectively). Low-to-moderate-intensity statins also had
      significant reductions in the risk of amputation and mortality (hazard ratio
      amputation, 0.81; 95% confidence interval, 0.75- 0.86; hazard ratio death, 0.83;
      95% confidence interval, 0.81-0.86) in comparison with no statins (antiplatelet
      therapy only), but effect size was significantly weaker than the high-intensity
      statins (P<0.001). The association of high-intensity statins with lower
      amputation and death risk remained significant and robust in propensity score
      matched, sensitivity, and subgroup analyses. CONCLUSIONS: Statins, especially
      high-intensity formulations, are underused in patients with PAD. This is the
      first population-based study to show that high-intensity statin use at the time
      of PAD diagnosis is associated with a significant reduction in limb loss and
      mortality in comparison with low-to-moderate-intensity statin users, and patients
      treated only with antiplatelet medications but not with statins, as well.

PMID- 29330215
TI  - MicroRNA-195 Regulates Metabolism in Failing Myocardium Via Alterations in
      Sirtuin 3 Expression and Mitochondrial Protein Acetylation.
AB  - BACKGROUND: Heart failure leads to mitochondrial dysfunction and metabolic
      abnormalities of the failing myocardium coupled with an energy-depleted state and
      cardiac remodeling. The mitochondrial deacetylase sirtuin 3 (SIRT3) plays a
      pivotal role in the maintenance of mitochondrial function through regulating the
      mitochondrial acetylome. It is interesting to note that unique cardiac and
      systemic microRNAs have been shown to play an important role in cardiac
      remodeling by modulating key signaling elements in the myocardium. METHODS:
      Cellular signaling was analyzed in human cardiomyocyte-like AC16 cells, and
      acetylation levels in rodent models of SIRT3-/-and transgenic microRNA-195 (miR
      195) overexpression were compared with wild type. Luciferase assays, Western
      blotting, immunoprecipitation assays, and echocardiographic analysis were
      performed. Enzymatic activities of pyruvate dehydrogenase (PDH) and ATP synthase
      were measured. RESULTS: In failing human myocardium, we observed induction of miR
      195 along with decreased expression of the mitochondrial deacetylase SIRT3 that
      was associated with increased global protein acetylation. We further investigated
      the role of miR-195 in SIRT3-mediated metabolic processes and its impact on
      regulating enzymes involved in deacetylation. Proteomic analysis of the total
      acetylome showed increased overall acetylation, and specific lysine acetylation
      of 2 central mitochondrial metabolic enzymes, PDH and ATP synthase, as well. miR
      195 downregulates SIRT3 expression through direct 3'-untranslated region
      targeting. Treatments with either sirtuin inhibitor nicotinamide, small
      interfering RNA-mediated SIRT3 knockdown or miR-195 overexpression enhanced
      acetylation of PDH complex and ATP synthase. This effect diminished PDH and ATP
      synthase activity and impaired mitochondrial respiration.SIRT3-/- and miR-195
      transgenic mice consistently showed enhanced global protein acetylation,
      including PDH complex and ATP synthase, associated with decreased enzymatic
      activity. CONCLUSIONS: Altogether, these data suggest that increased levels of
      miR-195 in failing myocardium regulate a novel pathway that involves direct SIRT3
      suppression and enzymatic inhibition via increased acetylation of PDH and ATP
      synthase that are essential for cardiac energy metabolism.

PMID- 29330216
TI  - Is placebo response in antidepressant trials rising or not? A reanalysis of
      datasets to conclude this long-lasting controversy.
AB  - It had long been believed that placebo response rates in antidepressant trials
      have been increasing and that they were responsible for rising numbers of so
      called failed antidepressant trials. Two recent systematic reviews examined this
      issue and reached completely opposite findings. Furukawa and colleagues in a
      paper published in 2016 found that the placebo response rates are stable since
      1991 and the apparent increase up to 2000 was confounded by changes in trial
      design features. By contrast, Khan and colleagues more recently concluded that
      placebo response rates had grown steadily in the past 30 years. The two reviews
      differed in the datasets they used, definitions of placebo response and
      statistical analyses. In this perspective article, we examined if such
      differences were responsible for the two reviews' contrasting conclusions. Our
      reanalyses confirmed our previous results. We found that in any dataset and for
      any placebo response definition, there was no increase in placebo response over
      the years when the analysis was adjusted for the confounders related to study
      design features or when it was limited to studies published after 1990s. We
      conclude that placebo response in antidepressant trials has remained stable for
      the past 25 years, during which time the large majority of the studies have come
      to share similar design features.

PMID- 29330217
TI  - A systematic review of network meta-analyses for pharmacological treatment of
      common mental disorders.
AB  - QUESTION: Network meta-analyses (NMAs) of treatment efficacy across different
      pharmacological treatments help inform clinical decision-making, but their
      methodological quality may vary a lot depending also on the quality of the
      included primary studies. We therefore conducted a systematic review of NMAs of
      pharmacological treatment for common mental disorders in order to assess the
      methodological quality of these NMAs, and to relate study characteristics to the
      rankings of efficacy and tolerability. STUDY SELECTION AND ANALYSIS: We searched
      three databases for NMAs of pharmacological treatment used in major depression,
      generalised anxiety disorder (GAD), social anxiety disorder (SAD), post-traumatic
      stress disorder (PTSD), obsessive-compulsive disorder (OCD) and specific
      phobia.Studies were appraised using the International Society for
      Pharmacoeconomics and Outcomes Research checklist of good research practices for
      indirect-treatment-comparison and network-meta-analysis studies. FINDINGS: Twenty
      NMAs were eligible for inclusion. The number of randomised controlled trials per
      NMA ranged from 11 to 234, and included between 801 to more than 26 000
      participants. Overall, antidepressants were found to be efficacious and tolerable
      agents for several disorders based on rankings (45%) or statistical significance
      (55%). The majority of NMAs in this review adhered to guidelines by including a
      network diagram (70%), assessing consistency (75%), making use of a random
      effects model (75%), providing information on the model used to fit the data
      (75%) and adjusting for covariates (75%). CONCLUSIONS: The 20 NMAs of depression
      and anxiety disorders, PTSD and/or OCD included in this review demonstrate some
      methodological strengths in comparison with the larger body of published NMAs for
      medical disorders, support current treatment guidelines and help inform clinical
      decision-making.

PMID- 29330218
TI  - A Study on Pharmacokinetics of Bosentan with Systems Modeling, Part 1:
      Translating Systemic Plasma Concentration to Liver Exposure in Healthy Subjects.
AB  - Understanding liver exposure of hepatic transporter substrates in clinical
      studies is often critical, as it typically governs pharmacodynamics, drug-drug
      interactions, and toxicity for certain drugs. However, this is a challenging task
      since there is currently no easy method to directly measure drug concentration in
      the human liver. Using bosentan as an example, we demonstrate a new approach to
      estimate liver exposure based on observed systemic pharmacokinetics from clinical
      studies using physiologically based pharmacokinetic modeling. The prediction was
      verified to be both accurate and precise using sensitivity analysis. For
      bosentan, the predicted pseudo steady-state unbound liver-to-unbound systemic
      plasma concentration ratio was 34.9 (95% confidence interval: 4.2, 50). Drug-drug
      interaction (i.e., CYP3A and CYP2B6 induction) and inhibition of hepatic
      transporters (i.e., bile salt export pump, multidrug resistance-associated
      proteins, and sodium-taurocholate cotransporting polypeptide) were predicted
      based on the estimated unbound liver tissue or plasma concentrations. With
      further validation and refinement, we conclude that this approach may serve to
      predict human liver exposure and complement other methods involving tissue biopsy
      and imaging.

PMID- 29330219
TI  - A Study on Pharmacokinetics of Bosentan with Systems Modeling, Part 2:
      Prospectively Predicting Systemic and Liver Exposure in Healthy Subjects.
AB  - Predicting human pharmacokinetics of novel compounds is a critical step in drug
      discovery and clinical study design but continues to be a challenging task for
      hepatic transporter substrates, particularly in predicting their liver exposures.
      In this study, using bosentan as an example, we prospectively predicted systemic
      exposure and the (pseudo) steady-state unbound liver-to-unbound plasma ratio
      (Kpuu) in healthy subjects using 1) a mechanistic approach solely based on in
      vitro hepatocyte assays and 2) an approach based on hepatic process rates from
      monkey in vivo data but Michaelis-Menten constants from in vitro data. Both
      methods reasonably match the observed human systemic time course data, but the
      second method leads to better prediction accuracy. In addition, the second method
      can predict a human Kpuu value that is close to the value deduced using clinical
      data. We also generated rat and monkey liver Kpuu values in terminal studies.
      However, these directly measured animal values are different from the deduced
      human value.

PMID- 29330220
TI  - Regulation of Drug Metabolism by the Interplay of Inflammatory Signaling,
      Steatosis, and Xeno-Sensing Receptors in HepaRG Cells.
AB  - Nonalcoholic fatty liver disease (NAFLD), which is characterized by triglyceride
      deposition in hepatocytes resulting from imbalanced lipid homeostasis, is of
      increasing concern in Western countries, along with progression to nonalcoholic
      steatohepatitis (NASH), liver fibrosis, and cirrhosis. Previous studies suggest a
      complex, mutual influence of hepatic fat accumulation, NASH-related inflammatory
      mediators, and drug-sensing receptors regulating xenobiotic metabolism. Here, we
      investigated the suitability of human HepaRG hepatocarcinoma cells as a model for
      NAFLD and NASH. Cells were incubated for up to 14 days with an oleate/palmitate
      mixture (125 uM each) and/or with 10 ng/ml of the inflammatory mediator
      interleukin-6 (IL-6). Effects of these conditions on the regulation of drug
      metabolism were studied using xenobiotic agonists of the aryl hydrocarbon
      receptor (AHR), pregnane X receptor (PXR), constitutive androstane receptor
      (CAR), nuclear factor (erythroid-derived 2)-like 2, and peroxisome proliferator
      activated receptor alpha (PPARalpha). Results underpin the suitability of HepaRG
      cells for NAFLD- and NASH-related research and constitute a broad-based analysis
      of the impact of hepatic fatty acid accumulation and inflammation on drug
      metabolism and its inducibility by xenobiotics. IL-6 exerted pronounced negative
      regulatory effects on basal as well as on PXR-, CAR-, and PPARalpha-, but not AHR
      dependent induction of drug-metabolizing enzymes. This inhibition was related to
      diminished transactivation potential of the respective receptors rather than to
      reduced transcription of nuclear receptor-encoding mRNAs. The most striking
      effects of IL-6 and/or fatty acid treatment were observed in HepaRG cells after
      14 days of treatment, making these cultures appear a suitable model for studying
      the relationship of fatty acid accumulation, inflammation, and xenobiotic-induced
      drug metabolism.

PMID- 29330221
TI  - Minimal/measurable residual disease in AML: a consensus document from the
      European LeukemiaNet MRD Working Party.
AB  - Measurable residual disease (MRD; previously termed minimal residual disease) is
      an independent, postdiagnosis, prognostic indicator in acute myeloid leukemia
      (AML) that is important for risk stratification and treatment planning, in
      conjunction with other well-established clinical, cytogenetic, and molecular data
      assessed at diagnosis. MRD can be evaluated using a variety of multiparameter
      flow cytometry and molecular protocols, but, to date, these approaches have not
      been qualitatively or quantitatively standardized, making their use in clinical
      practice challenging. The objective of this work was to identify key clinical and
      scientific issues in the measurement and application of MRD in AML, to achieve
      consensus on these issues, and to provide guidelines for the current and future
      use of MRD in clinical practice. The work was accomplished over 2 years, during 4
      meetings by a specially designated MRD Working Party of the European LeukemiaNet.
      The group included 24 faculty with expertise in AML hematopathology, molecular
      diagnostics, clinical trials, and clinical medicine, from 19 institutions in
      Europe and the United States.

PMID- 29330222
TI  - Increased sympathovagal imbalance evaluated by heart rate variability is
      associated with decreased T2* MRI and left ventricular function in transfusion
      dependent thalassemia patients.
AB  - Early detection of iron overload cardiomyopathy is an important strategy for
      decreasing the mortality rate of patients with transfusion-dependent thalassemia
      (TDT). Although cardiac magnetic resonance (CMR) T2* is effective in detecting
      cardiac iron deposition, it is costly and not generally available. We
      investigated whether heart rate variability (HRV) can be used as a screening
      method of iron overload cardiomyopathy in TDT patients. HRV, evaluated by 24-h
      Holter monitoring, non-transferrin bound iron (NTBI), serum ferritin, left
      ventricular (LV) ejection fraction (LVEF), and CMR-T2* were determined. Patients
      with a cardiac iron overload condition had a significantly higher low
      frequency/high frequency (LF/HF) ratio than patients without a cardiac iron
      overload condition. Log-serum ferritin (r = -0.41, P=0.008), serum NTBI (r = 
      0.313, P=0.029), and LF/HF ratio (r = -0.286, P=0.043) showed a significant
      correlation with CMR-T2*, however only the LF/HF ratio was significantly
      correlated with LVEF (r = -0.264, P=0.043). These significant correlations
      between HRV and CMR-T2* and LVEF in TDT confirmed the beneficial role of HRV as a
      potential early screening tool of cardiac iron overload in thalassemia patients,
      especially in a medical center in which CMR T2* is not available. A larger number
      of TDT patients with cardiac iron overload are needed to confirm this finding.

PMID- 29330223
TI  - The antioxidant xanthorrhizol prevents amyloid-beta-induced oxidative
      modification and inactivation of neprilysin.
AB  - Activity of neprilysin (NEP), the major protease which cleaves amyloid-beta
      peptide (Abeta), is reportedly reduced in the brains of patients with Alzheimer's
      disease (AD). Accumulation of Abeta generates reactive oxygen species (ROS) such
      as 4-hydroxynonenal (HNE), and then reduces activities of Abeta-degrading enzymes
      including NEP. Xanthorrhizol (Xan), a natural sesquiterpenoid, has been reported
      to possess antioxidant and anti-inflammatory properties. The present study
      examined the effects of Xan on HNE- or oligomeric Abeta42-induced oxidative
      modification of NEP protein. Xan was added to the HNE- or oligomeric Abeta42
      treated SK-N-SH human neuroblastoma cells and then levels, oxidative modification
      and enzymatic activities of NEP protein were measured. Increased HNE levels on
      NEP proteins and reduced enzymatic activities of NEP were observed in the HNE- or
      oligomeric Abeta42-treated cells. Xan reduced HNE levels on NEP proteins and
      preserved enzymatic activities of NEP in HNE- or oligomeric Abeta42-treated
      cells. Xan reduced Abeta42 accumulation and protected neurones against oligomeric
      Abeta42-induced neurotoxicity through preservation of NEP activities. These
      findings indicate that Xan possesses therapeutic potential for the treatment of
      neurodegenerative diseases, including AD, and suggest a potential mechanism for
      the neuroprotective effects of antioxidants for the prevention of AD.

PMID- 29330224
TI  - Vitamin D ameliorates impaired wound healing in streptozotocin-induced diabetic
      mice by suppressing NF-kappaB-mediated inflammatory genes.
AB  - Diabetic wounds are characterized by delayed wound healing due to persistent
      inflammation and excessive production of reactive oxygen species. Vitamin D,
      which is well acknowledged to enhance intestinal calcium absorption and increase
      in plasma calcium level, has recently been shown to display beneficial effects in
      various vascular diseases by promoting angiogenesis and inhibiting inflammatory
      responses. However, the role of Vitamin D in diabetic wound healing is still
      unclear. In the present study, we investigated the role of Vitamin D in cutaneous
      wound healing in streptozotocin (STZ)-induced diabetic mice. Four weeks after
      injection of STZ, a full thickness excisional wound was created with a 6-mm
      diameter sterile biopsy punch on the dorsum of the mice. Vitamin D was given
      consecutively for 14 days by intraperitoneal injection. Vitamin D supplementation
      significantly accelerated wound healing in diabetic mice and improved the healing
      quality as assessed by measuring the wound closure rate and histomorphometric
      analyses. By monitoring the level of pro-inflammatory cytokines tumor necrosis
      factor-alpha (TNF-alpha), interleukin (IL) 6 (IL-6), IL-1beta) in the wounds,
      reduced inflammatory response was found in VD treatment group. Furthermore,
      nuclear factor kappaB (NF-kappaB) pathway was found to be involved in the process
      of diabetic wound healing by assessing the relative proteins in diabetic wounds.
      Vitamin D supplementation obviously suppressed NF-kappaB pathway activation.
      These results demonstrated that Vitamin D improves impaired wound healing in STZ
      induced diabetic mice through suppressing NF-kappaB-mediated inflammatory gene
      expression.

PMID- 29330225
TI  - GENETICS IN ENDOCRINOLOGY: Genetic counseling for congenital hypogonadotropic
      hypogonadism and Kallmann syndrome: new challenges in the era of oligogenism and
      next-generation sequencing.
AB  - Congenital hypogonadotropic hypogonadism (CHH) and Kallmann syndrome (KS) are
      rare, related diseases that prevent normal pubertal development and cause
      infertility in affected men and women. However, the infertility carries a good
      prognosis as increasing numbers of patients with CHH/KS are now able to have
      children through medically assisted procreation. These are genetic diseases that
      can be transmitted to patients' offspring. Importantly, patients and their
      families should be informed of this risk and given genetic counseling. CHH and KS
      are phenotypically and genetically heterogeneous diseases in which the risk of
      transmission largely depends on the gene(s) responsible(s). Inheritance may be
      classically Mendelian yet more complex; oligogenic modes of transmission have
      also been described. The prevalence of oligogenicity has risen dramatically since
      the advent of massively parallel next-generation sequencing (NGS) in which tens,
      hundreds or thousands of genes are sequenced at the same time. NGS is medically
      and economically more efficient and more rapid than traditional Sanger sequencing
      and is increasingly being used in medical practice. Thus, it seems plausible that
      oligogenic forms of CHH/KS will be increasingly identified making genetic
      counseling even more complex. In this context, the main challenge will be to
      differentiate true oligogenism from situations when several rare variants that do
      not have a clear phenotypic effect are identified by chance. This review aims to
      summarize the genetics of CHH/KS and to discuss the challenges of oligogenic
      transmission and also its role in incomplete penetrance and variable expressivity
      in a perspective of genetic counseling.

PMID- 29330226
TI  - Mitotane treatment in patients with metastatic testicular Leydig cell tumor
      associated with severe androgen excess.
AB  - Mitotane (o,p'DDD) is established in the adjuvant and advanced-stage treatment of
      adrenocortical carcinoma and counteracts both tumor growth and tumor-related
      steroid production. Both the adrenal glands and the gonads are steroidogenically
      active organs and share a common embryogenic origin. Here, we describe the
      effects of mitotane in two patients with metastatic Leydig cell tumor (LCT) of
      the testes and associated severe androgen excess (serum testosterone 93 and 88
      nmol/L, respectively; male reference range 7-27 nmol/L). Both men suffered from
      severe restlessness, insomnia and irritability, which they described as
      intolerable and disrupting normal life activities. Urinary steroid profiling by
      gas chromatography-mass spectrometry (GC-MS) confirmed excess androgen production
      and revealed concurrent overproduction of glucocorticoids and glucocorticoid
      precursors, which under physiological conditions are produced only by the adrenal
      glands but not by the gonads. In a palliative approach, they were commenced on
      mitotane, which achieved swift control of the hormone excess and the debilitating
      clinical symptoms, restoring normal quality of life. GC-MS demonstrated
      normalization of steroid production and decreased 5alpha-reductase activity,
      resulting in decreased androgen activation, and imaging demonstrated disease
      stabilization for 4-10 months. In conclusion, mitotane can be highly effective in
      controlling steroid excess in metastatic LCTs, with anti-tumor activity in some
      cases.

PMID- 29330227
TI  - Earlier post-operative hypocortisolemia may predict durable remission from
      Cushing's disease.
AB  - CONTEXT: Achievement of hypocortisolemia following transsphenoidal surgery (TSS)
      for Cushing's disease (CD) is associated with successful adenoma resection.
      However, up to one-third of these patients recur. OBJECTIVE: We assessed whether
      delay in reaching post-operative cortisol nadir may delineate patients at risk of
      recurrence for CD following TSS. METHODS: A retrospective review of 257 patients
      who received 291 TSS procedures for CD at NIH, between 2003 and 2016. Early
      biochemical remission (serum cortisol nadir <5 MUg/dL) was confirmed with
      endocrinological and clinical follow-up. Recurrence was detected by laboratory
      testing, clinical stigmata or medication dependence during a median follow-up of
      11 months. RESULTS: Of the 268 unique admissions, remission was recorded in 241
      instances. Recurrence was observed in 9% of these cases with cortisol nadir <=5
      MUg/dL and 6% of cases with cortisol nadir <=2 MUg/dL. The timing of
      hypocortisolemia was critical in detecting late recurrences. Morning POD-1
      cortisol <3.3 MUg/dL was 100% sensitive in predicting durable remission and
      morning POD-3 cortisol >=18.5 MUg/dL was 98.6% specific in predicting remote
      recurrence. AUROC analysis revealed that hypocortisolemia <=5 ug/dL before 15 h
      (post-operative) had 95% sensitivity and an NPV of 0.98 for durable remission.
      Serum cortisol level <=2 ug/dL, when achieved before 21 h, improved sensitivity
      to 100%. CONCLUSIONS: In our cohort, early, profound hypocortisolemia could be
      used as a clinical prediction tool for durable remission. Achievement of
      hypocortisolemia <=2 ug/dL before 21 post-operative hours appeared to accurately
      predict durable remission in the intermediate term.

PMID- 29330229
TI  - Determining the educational impact of the introduction of practice-based small
      group learning within an intraprofessional group of doctors.
AB  - INTRODUCTION: Practice-Based Small Group Learning (PBSGL) is a system for
      continuing professional development introduced into Wessex Region Defence Primary
      Healthcare (DPHC) as the Salisbury Plain PBSGL group in 2012. This is a mixed
      intraprofessional group comprising general practitioners (GPs), GP trainers,
      general practice specialist registrars (GPSTs) and general duties medical
      officers (GDMOs). METHODS: An anonymised online questionnaire and thematic
      analysis was undertaken to assess the educational impact of PBSGL in such a mixed
      role group reflecting military general practice. RESULTS: A positive effect of
      PBSGL was demonstrated and further enhanced by the intraprofessional composition.
      Positive peer support effects were demonstrated for all members of the cohort
      regardless of role. CONCLUSION: PBSGL is an essential pillar for supporting all
      doctors working within DPHC. Further qualitative evaluation of cohorts of GDMOs,
      GPSTs and mixed-role groups as well as the development of standardised
      questionnaires is recommended.

PMID- 29330230
TI  - Reducing sedentary behaviour to decrease chronic low back pain: the stand back
      randomised trial.
AB  - OBJECTIVE: The Stand Back study evaluated the feasibility and effects of a
      multicomponent intervention targeting reduced prolonged sitting and pain self
      management in desk workers with chronic low back pain (LBP). METHODS: This
      randomised controlled trial recruited 27 individuals with chronic LBP, Oswestry
      Disability Index (ODI) >10% and desk jobs (sitting >=20 hours/week). Participants
      were randomised within strata of ODI (>10%-<20%, >=20%) to receive bimonthly
      behavioural counselling (in-person and telephone), a sit-stand desk attachment, a
      wrist-worn activity-prompting device and cognitive behavioural therapy for LBP
      self-management or control. Self-reported work sitting time, visual analogue
      scales (VAS) for LBP and the ODI were assessed by monthly, online questionnaires
      and compared across intervention groups using linear mixed models. RESULTS:
      Baseline mean (SD) age was 52 (11) years, 78% were women, and ODI was 24.1
      (10.5)%. Across the 6-month follow-up in models adjusted for baseline value, work
      sitting time was 1.5 hour/day (P<0.001) lower comparing intervention to controls.
      Also across follow-up, ODI was on average 8 points lower in intervention versus
      control (P=0.001). At 6 months, the relative decrease in ODI from baseline was
      50% in intervention and 14% in control (P=0.042). LBP from VAS was not
      significantly reduced in intervention versus control, though small-to-moderate
      effect sizes favouring the intervention were observed (Cohen's d ranged from 0.22
      to 0.42). CONCLUSION: An intervention coupling behavioural counselling targeting
      reduced sedentary behaviour and pain self-management is a translatable treatment
      strategy that shows promise for treating chronic LBP in desk-bound employees.
      TRIAL REGISTRATION NUMBER: NCT0224687; Pre-results.

PMID- 29330231
TI  - Some clues for studying long-term health effects of oil spills.

PMID- 29330228
TI  - Treatment of aggressive pituitary tumours and carcinomas: results of a European
      Society of Endocrinology (ESE) survey 2016.
AB  - OBJECTIVE: To collect outcome data in a large cohort of patients with aggressive
      pituitary tumours (APT)/carcinomas (PC) and specifically report effects of
      temozolomide (TMZ) treatment. DESIGN: Electronic survey to ESE members Dec 2015
      Nov 2016. RESULTS: Reports on 166 patients (40 PC, 125 APT, 1 unclassified) were
      obtained. Median age at diagnosis was 43 (range 4-79) years. 69% of the tumours
      were clinically functioning, and the most frequent immunohistochemical subtype
      were corticotroph tumours (45%). Ki-67 index did not distinguish APT from PC,
      median 7% and 10% respectively. TMZ was first-line chemotherapy in 157 patients.
      At the end of the treatment (median 9 cycles), radiological evaluation showed
      complete response (CR) in 6%, partial response (PR) in 31%, stable disease (SD)
      in 33% and progressive disease in 30%. Response was more frequent in patients
      receiving concomitant radiotherapy and TMZ. CR was seen only in patients with low
      MGMT expression. Clinically functioning tumours were more likely to respond than
      non-functioning tumours, independent of MGMT status. Of patients with CR, PR and
      SD, 25, 40 and 48% respectively progressed after a median of 12-month follow-up.
      Other oncological drugs given as primary treatment and to TMZ failures resulted
      in PR in 20%. CONCLUSION: This survey confirms that TMZ is established as first
      line chemotherapeutic treatment of APT/PC. Clinically functioning tumours, low
      MGMT and concurrent radiotherapy were associated with a better response. The
      limited long-term effect of TMZ and the poor efficacy of other drugs highlight
      the need to identify additional effective therapies.

PMID- 29330232
TI  - Interventions Must Be Realistic to Be Useful and Completed in Family Medicine.
AB  - Being realistic while helping our patients is this issue's theme. Given the
      volume of tasks required in family medicine, recommendations for improvements in
      direct care or care measurement cannot just be evidence-based but must also be
      realistic. On the list of realistic: ordering antipsychotics for symptoms of
      dementia in the elderly, despite recommendations to not do so; ordering
      antidepressants without fear that the patient could develop hypertension; mental
      health care providers in primary care offices; forced choice for opioid
      management; plus agenda setting for visit efficiency. Not yet realistic: trigger
      tools to identify adverse events, and pharmacist recommendations related to pain
      management before opioid visits. Pneumococcal vaccine compliance is only
      realistic if recommendations are not recurrently changed, are paid for, and if
      prior immunizations are known. Increasing task delegation to prevent clinician
      burnout is not realistic if it burns out the nurses, or if the helpful scribes
      cannot be afforded. Helpful, yet questionably realistic: Primary care clinician
      involvement for patients in intensive care units and their families, and problem
      solving therapy by family physicians. And, let us add 'frightening': few
      international medical school graduates to serve the underserved. The most
      frequent diagnoses and most critical diagnoses in family medicine are elucidated.

PMID- 29330233
TI  - A State Chapter Perspective on Burnout and Resiliency.

PMID- 29330234
TI  - Burnout in Young Family Physicians: Variation Across States.
AB  - Family physicians 3 years out of training report high rates of emotional
      exhaustion and depersonalization, symptoms of burnout, with considerable
      variation between states. High rates of burnout among new family physicians is
      concerning and significant state-level variation suggests that state-related
      factors may contribute to or reduce burnout.

PMID- 29330235
TI  - Primary Care Physician Perspectives about Antipsychotics and Other Medications
      for Symptoms of Dementia.
AB  - BACKGROUND: Guidelines, policies, and warnings have been applied to reduce the
      use of medications for behavioral and psychological symptoms of dementia (BPSD).
      Because of rare dangerous side effects, antipsychotics have been singled out in
      these efforts. However, antipsychotics are still prescribed "off label" to
      hundreds of thousands of seniors residing in nursing homes and communities. Our
      objective was to evaluate how and why primary-care physicians (PCPs) employ
      nonpharmacologic strategies and drugs for BPSD. METHODS: Semi-structured
      interviews analyzed via template, immersion and crystallization, and thematic
      development of 26 PCPs (16 family practice, 10 general internal medicine) in full
      time primary-care practice for at least 3 years in Northwestern Virginia.
      RESULTS: PCPs described 4 major themes regarding BPSD management: (1)
      nonpharmacologic methods have substantial barriers; (2) medication use is not
      constrained by those barriers and is perceived as easy, efficacious, reasonably
      safe, and appropriate; (3) pharmacologic policies decrease the use of targeted
      medications, including antipsychotics, but also have unintended consequences such
      as increased use of alternative risky medications; and (4) PCPs need practical
      evidence-based guidelines for all aspects of BPSD management. CONCLUSIONS: PCPs
      continue to prescribe medications because they meet patient-oriented goals and
      because PCPs perceive drugs, including antipsychotics and their alternatives, to
      be more effective and less dangerous than evidence suggests. To optimally treat
      BPSD, PCPs need supportive verified prescribing guidelines and access to
      nonpharmacologic modalities that are as affordable, available, and efficacious as
      drugs; these require and deserve significant additional research and payer
      support. Community PCPs should be included in BPSD policy and guideline
      development.

PMID- 29330236
TI  - Antidepressants and Incident Hypertension in Primary Care Patients.
AB  - OBJECTIVE: Many ADMs can alter blood pressure (BP), but the research on the
      effect of antidepressant medication (ADMs) on incident hypertension is mixed. We
      investigated whether the use of ADMs was associated with the subsequent
      development of hypertension. METHODS: A retrospective cohort study was conducted
      using electronic medical record data from 6224 patients with primary care visits
      from 2008 to 2015. Prescription orders were used to identify ADM use, and
      hypertension was defined by medical record diagnosis. Using package insert
      warnings, a 3-level ADM exposure variable was created: ADMs that increase BP (ADM
      BP+), ADMs that do not increase BP, and no ADM. Unadjusted and adjusted Cox
      proportional hazard models were computed to estimate the association between the
      ADM exposure and incident hypertension. RESULTS: Unadjusted results revealed that
      ADM BP+ use compared with the no ADM group was significantly associated with
      incident hypertension (hazard ratio, 1.30; 95% confidence interval, 1.08-1.57).
      After adjusting for covariates, ADM BP+ use was no longer significantly
      associated with incident hypertension (hazard ratio, 1.20; 95% confidence
      interval, 0.97-1.49). CONCLUSIONS: Commonly used ADMs were not associated with
      incident hypertension after controlling for other factors associated with ADM use
      and hypertension. Research on potential dose and duration effects is warranted.

PMID- 29330237
TI  - 'The Hand on the Doorknob': Visit Agenda Setting by Complex Patients and Their
      Primary Care Physicians.
AB  - BACKGROUND: Choosing which issues to discuss in the limited time available during
      primary care visits is an important task for complex patients with chronic
      conditions. DESIGN, SETTING, AND PARTICIPANTS: We conducted sequential interviews
      with complex patients (n = 40) and their primary care physicians (n = 17) from 3
      different health systems to investigate how patients and physicians prepare for
      visits, how visit agendas are determined, and how discussion priorities are
      established during time-limited visits. KEY RESULTS: Visit flow and alignment
      were enhanced when both patients and physicians were effectively prepared before
      the visit, when the patient brought up highest-priority items first, the
      physician and patient worked together at the beginning of the visit to establish
      the visit agenda, and other team members contributed to agenda setting. A range
      of factors were identified that undermined the ability of patient and physicians
      to establish an efficient working agenda: the most prominent were time pressure
      and short visit lengths, but also included differing visit expectations, patient
      hesitancy to bring up embarrassing concerns, electronic medical
      record/documentation requirements, differences balancing current symptoms versus
      future medical risk, nonactionable items, differing philosophies about
      medications and lifestyle interventions, and difficulty by patients in
      prioritizing their top concerns. CONCLUSIONS: Primary care patients and their
      physicians adopt a range of different strategies to address the time constraints
      during visits. The primary factor that supported well-aligned visits was the
      ability for patients and physicians to proactively negotiate the visit agenda at
      the beginning of the visit. Efforts to optimize care within time-constrained
      systems should focus on helping patients more effectively prepare for visits.
      Physicians should ask for the patient's agenda early, explain visit parameters,
      establish a reasonable number of concerns that can be discussed, and collaborate
      on a plan to deal with concerns that cannot be addressed during the visit.

PMID- 29330238
TI  - Changing Patterns of Mental Health Care Use: The Role of Integrated Mental Health
      Services in Veteran Affairs Primary Care.
AB  - OBJECTIVE: Aiming to foster timely, high-quality mental health care for Veterans,
      VA's Primary Care-Mental Health Integration (PC-MHI) embeds mental health
      specialists in primary care and promotes care management for depression. PC-MHI
      and patient-centered medical home providers work together to provide the bulk of
      mental health care for primary care patients with low-to-moderate-complexity
      mental health conditions. This study examines whether increasing primary care
      clinic engagement in PC-MHI services is associated with changes in patient health
      care utilization and costs. METHODS: We performed a retrospective longitudinal
      cohort study of primary care patients with identified mental health needs in 29
      Southern California VA clinics from October 1, 2008 to September 30, 2013, using
      electronic administrative data (n = 66,638). We calculated clinic PC-MHI
      engagement as the proportion of patients receiving PC-MHI services among all
      primary care clinic patients in each year. Capitalizing on variation in PC-MHI
      engagement across clinics, our multivariable regression models predicted annual
      patient use of 1) non-primary care based mental health specialty (MHS) visits, 2)
      total mental health visits (ie, the sum of MHS and PC-MHI visits), and 3) health
      care utilization and costs. We controlled for year- and clinic-fixed effects,
      other clinic interventions, and patient characteristics. RESULTS: Median clinic
      PC-MHI engagement increased by 8.2 percentage points over 5 years. At any given
      year, patients treated at a clinic with 1 percentage-point higher PC-MHI
      engagement was associated with 0.5% more total mental health visits (CI, 0.18% to
      0.90%; P = .003) and 1.0% fewer MHS visits (CI, -1.6% to -0.3%; P = .002); this
      is a substitution rate, at the mean, of 1.5 PC-MHI visits for each MHS visit.
      There was no PC-MHI effect on other health care utilization and costs.
      CONCLUSIONS: As intended, greater clinic engagement in PC-MHI services seems to
      increase realized accessibility to mental health care for primary care patients,
      substituting PC-MHI for MHS visits, without increasing acute care use or total
      costs. Thus, PC-MHI services within primary care clinics may improve mental
      health care value at the patient population level. More research is needed to
      understand the relationship between clinic PC-MHI engagement and clinical quality
      of mental health care.

PMID- 29330239
TI  - One Year of Family Physicians' Observations on Working with Medical Scribes.
AB  - PURPOSE: The immense clerical burden felt by physicians is one of the leading
      causes of burnout. Scribes are increasingly being used to help alleviate this
      burden, yet few published studies investigate how scribes affect physicians'
      daily work, attitudes and behaviors, and relationships with patients and the
      workplace. METHODS: Using a longitudinal observational design, data were
      collected, over 1 year, from 4 physicians working with 2 scribes at a single
      academic family medicine practice. Physician experience was measured by open
      ended written reflections requested after each 4-hour clinic session. A data
      driven codebook was generated using a constant comparative method with grounded
      theory approach. RESULTS: A total of 361 physician reflections were completed,
      yielding 150 distinct excerpts; 289 codes were assigned. The 11 themes that
      emerged were further categorized under 4 domains. The most frequently recurring
      domain was clinic operations, which comprised 51.6% of the codes. Joy of
      practice, quality of care, and patient experience comprised 22.1%, 16.3%, and
      10.0% of the codes, respectively. CONCLUSIONS: Our study suggests that
      integrating scribes into a primary care clinic can produce positive outcomes that
      go beyond reducing clerical burden for physicians. Scribes may benefit patient
      experience, quality of care, clinic operations, and joy of practice.

PMID- 29330240
TI  - Structured Management of Chronic Nonmalignant Pain with Opioids in a Rural
      Primary Care Office.
AB  - INTRODUCTION: The use of opioid medication for nonmalignant chronic pain (NMCP)
      increased dramatically during the last 20 years. There have been regulatory
      changes implemented to reduce the risk of harm to both patients and society. Much
      of the burden of monitoring these patients is falling on primary care physicians
      (PCPs), who do not have the time or resources to handle what is entailed in a
      best-practice approach to NMCP. METHODS: A retrospective study was conducted with
      all patients on opioid medication for NMCP who were enrolled onto an individual
      PCP's practice. All were required to engage with a new care system. Patients had
      the option to remain on opioids, to wean opioids, or to transfer care. Patients
      who remained in the practice on opioids were required to have an office visit on
      a day dedicated solely to NMCP every 3 months. Each visit involved verifying the
      controlled substance contract, a urine drug screen, board of pharmacy monitoring,
      pain-targeted history and physical, calculation of the average morphine
      equivalents used, and evaluations of pain, functional status, and mood.
      Characteristics more likely to lead to weaning from opioids were monitored, as
      was the program effect on the patients remaining on opioids. RESULTS: With this
      practice model, 32 patients treated with opioids for NMCP were enrolled. Of
      these, 38% (n = 12) elected to wean opioids, 53% (n = 17) continued opioid
      medication, and 9% (n = 3) transferred care. Mean morphine equivalent mg/day was
      the prime determinant for ability to wean (17.01 mg/day) compared with
      maintaining (30.61 mg/day) (P = .0397; CI, 0.68 to 26.51). Patients maintaining
      opioid treatment showed no statistically significant change in any measured data
      point from beginning until end of the evaluation period. CONCLUSION: Given the
      choice of following a specific structured care system of opioid medication
      management or leaving the practice, most patients agreed to the structured
      system. This approach provided a high degree of compliance with controlled
      substance regulations and is associated with a reduced number of opioid
      prescriptions. Patients who were on lower doses of opioid medication are more
      likely to wean their use with this model.

PMID- 29330241
TI  - Primary Care Physician Involvement in Shared Decision Making for Critically Ill
      Patients and Family Satisfaction with Care.
AB  - PURPOSE: An intensive care unit (ICU) patient's primary care physician (PCP) may
      be able to assist family with certain ICU shared medical decisions. We explored
      whether families of patients in nonopen ICUs who nevertheless report involvement
      of a patient's PCP in medical decision making are more satisfied with ICU shared
      decision making than families who do not. METHODS: Between March 2013 and
      December 2015, we administered the Family Satisfaction in the ICU 24 survey to
      family members of adult neuroscience ICU patients. We compared the mean score for
      the survey subsection regarding shared decision making (graded on a 100-point
      scale), as well as individual survey items, between those who reported the
      patient's PCP involvement in any medical decision making versus those who did
      not. RESULTS: Among 263 respondents, there was no difference in mean overall
      decision-making satisfaction scores for those who reported involvement (81.1; SD
      = 15.2) versus those who did not (80.1; SD = 12.8; P = .16). However, a higher
      proportion reporting involvement felt completely satisfied with their 1)
      inclusion in the ICU decision making process (75.9% vs 61.4%; P = .055), and 2)
      control over the care of the patient (73.6% vs 55.6%; P = .02), with no
      difference regarding consistency of clinical information provided by the medical
      team (64.8% vs 63.5%; P = 1.00). CONCLUSIONS: Families who report involvement of
      a patient's PCP in medical decision making for critically ill patients may be
      more satisfied than those who do not with regard to specific aspects of ICU
      decision making. Further research would help understand how best to engage PCPs
      in shared decisions.

PMID- 29330242
TI  - Patient Perspectives on Discussions of Electronic Cigarettes in Primary Care.
AB  - PURPOSE: Patient preferences regarding the role of the primary care provider
      (PCP) in discussing electronic cigarette (e-cigarette) use are unknown. METHODS:
      We administered a cross-sectional survey to 568 adult patients in a family
      medicine clinic to explore e-cigarette use, sources of information on e
      cigarettes, perceived knowledge about e-cigarette health effects, views regarding
      PCP knowledge of e-cigarettes, interest in discussing e-cigarettes with PCPs and
      preferred format for e-cigarette information. We performed chi2 testing with a 2
      tailed P < .05 to assess associations between e-cigarette use and these measures.
      RESULTS: The prevalence of e-cigarette use was 10% for recent (<=30 days) use and
      29% for nonrecent (>30 days) use. Prevalence was significantly higher among those
      who were younger, less educated, or smoked cigarettes, but did not vary by sex or
      self-reported health status. Roughly one quarter of participants believed they
      were knowledgeable about the health effects of e-cigarettes, secondhand smoke,
      and quitting cigarettes. Sources of e-cigarette information included television
      advertisements (56.6%), friends and family (49.9%), or e-cigarette shops (25.5%),
      but included physician offices much less frequently (6.0%). Although 30.2%
      disagreed that their PCP knew a lot about e-cigarettes, 62.0% were comfortable
      discussing e-cigarettes with their PCP. However, only 25% of all patients wanted
      their PCP to discuss e-cigarettes with them, but 62.0% of recent e-cigarette
      users wanted such a discussion. Most preferred a brief discussion or handout to a
      lengthy discussion. CONCLUSION: PCPs were infrequent sources of information for
      patients regarding e-cigarette use. PCPs need evidence-based strategies to help
      them address e-cigarettes in primary care.

PMID- 29330243
TI  - Task Delegation and Burnout Trade-offs Among Primary Care Providers and Nurses in
      Veterans Affairs Patient Aligned Care Teams (VA PACTs).
AB  - PURPOSE: Appropriate delegation of clinical tasks from primary care providers
      (PCPs) to other team members may reduce employee burnout in primary care.
      However, (1) the extent to which delegation occurs within multidisciplinary
      teams, (2) factors associated with greater delegation, and (3) whether delegation
      is associated with burnout are all unknown. METHODS: We performed a national
      cross-sectional survey of Veterans Affairs (VA) PCP-nurse dyads in Department of
      VA primary care clinics, 4 years into the VA's patient-centered medical home
      initiative. PCPs reported the extent to which they relied on other team members
      to complete 15 common primary care tasks; paired nurses reported how much they
      were relied on to complete the same tasks. A composite score of task
      delegation/reliance was developed by taking the average of the responses to the
      15 questions. We performed multivariable regression to explore predictors of task
      delegation and burnout. RESULTS: Among 777 PCP-nurse dyads, PCPs reported
      delegating tasks less than nurses reported being relied on (PCP mean +/- standard
      deviation composite delegation score, 2.97+/- 0.64 [range, 1-4]; nurse composite
      reliance score, 3.26 +/- 0.50 [range, 1-4]). Approximately 48% of PCPs and 35% of
      nurses reported burnout. PCPs who reported more task delegation reported less
      burnout (odds ratio [OR], 0.62 per unit of delegation; 95% confidence interval
      [CI], 0.49-0.78), whereas nurses who reported being relied on more reported more
      burnout (OR, 1.83 per unit of reliance; 95% CI, 1.33-2.5). CONCLUSIONS: Task
      delegation was associated with less burnout for PCPs, whereas task reliance was
      associated with greater burnout for nurses. Strategies to improve work life in
      primary care by increasing PCP task delegation must consider the impact on
      nurses.

PMID- 29330245
TI  - Impact of Pharmacist Previsit Input to Providers on Chronic Opioid Prescribing
      Safety.
AB  - INTRODUCTION: Primary care providers (PCPs) account for half of opioid
      prescriptions, often feel chronic pain patients are challenging to manage, and
      there is wide variability in practice patterns. The purpose of this pilot study
      was to evaluate the impact of a previsit pharmacist review of high-risk patients
      treated with opioids for chronic pain on compliance to guideline recommendations
      at a family medicine residency clinic. METHODS: All adult patients with an
      appointment for chronic pain who were prescribed >50 morphine milligram
      equivalents (MMEs)/day had charts reviewed by a pharmacist before each
      appointment; recommendations were sent electronically to the provider before the
      appointment. After 4 months of implementation, each patient's chart was manually
      reviewed to gather outcome variables. The primary outcomes were the mean MMEs/day
      and pain scores. RESULTS: Pharmacist previsit recommendations were provided for
      45 patients. When comparing outcomes before and after intervention, the mean
      MMEs/day decreased by 14% (P < .001), with no change in pain scores (P = .783).
      Statistically significant improvements were noted in multiple other secondary
      opioid safety outcomes. CONCLUSION: Clinical pharmacists providing previsit
      recommendations was associated with decreased opioid utilization with no
      corresponding increase in pain scores and increased compliance to guideline
      recommendations.

PMID- 29330244
TI  - Primary Care Physicians' Struggle with Current Adult Pneumococcal Vaccine
      Recommendations.
AB  - INTRODUCTION: In 2012, the Advisory Committee on Immunization Practices
      recommended 13-valent pneumococcal conjugate vaccine (PCV13) in series with 23
      valent pneumococcal polysaccharide vaccine (PPSV23) for at-risk adults >=19; in
      2014, it expanded this recommendation to adults >=65. Primary care physicians'
      practice, knowledge, attitudes, and beliefs regarding these recommendations are
      unknown. METHODS: Primary care physicians throughout the U.S. were surveyed by E
      mail and post from December 2015 to January 2016. RESULTS: Response rate was 66%
      (617 of 935). Over 95% of respondents reported routinely assessing adults'
      vaccination status and recommending both vaccines. A majority found the current
      recommendations to be clear (50% "very clear," 38% "somewhat clear"). Twenty
      percent found the upfront cost of purchasing PCV13, lack of insurance coverage,
      inadequate reimbursement, and difficulty determining vaccination history to be
      "major barriers" to giving these vaccines. Knowledge of recommendations varied,
      with 83% identifying the PCV13 recommendation for adults >=65 and only 21%
      identifying the recommended interval between PCV13 and PPSV23 in an individual
      <65 at increased risk. CONCLUSIONS: Almost all surveyed physicians reported
      recommending both pneumococcal vaccines, but a disconnect seems to exist between
      perceived clarity and knowledge of the recommendations. Optimal implementation of
      these recommendations will require addressing knowledge gaps and reported
      barriers.

PMID- 29330246
TI  - The Accuracy of Trigger Tools to Detect Preventable Adverse Events in Primary
      Care: A Systematic Review.
AB  - PURPOSE: To understand the ability of trigger tools to detect preventable adverse
      events (pAEs) in the primary care outpatient setting using the Institute for
      Healthcare Improvement's (IHI) Outpatient Adverse Event Trigger Tool (IHI Tool).
      METHODS: The OVID MEDLINE and OVID MEDLINE In-process and non-Indexed citations
      databases were queried using controlled vocabulary and Medical Subject Headings
      related to the concepts "primary care" and "adverse events." Included articles
      were conducted in the outpatient setting, used at least 1 of the triggers
      identified in the IHI Tool, and identified pAEs of any type. Articles were
      selected for inclusion based first on assessment of titles then abstracts by 2
      trained reviewers independently, followed by full text review by 2 authors.
      RESULTS: Our search identified 6435 unique articles, and we included 15 in our
      review. The most common studied trigger was laboratory abnormalities. The most
      common pAEs were medication errors followed by unplanned hospitalizations. The
      effectiveness of triggers in identifying AEs varied widely. CONCLUSION: There is
      insufficient data on the IHI Tool and its use to identify pAEs in the general
      real-world outpatient setting. Health care providers of the primary care setting
      may benefit from better trigger tools and other methods to help them detect pAEs.
      More research is needed to further evaluate the effectiveness of trigger tools to
      reduce barriers of cost and time and improve patient safety.

PMID- 29330247
TI  - Frequency and Criticality of Diagnoses in Family Medicine Practices: From the
      National Ambulatory Medical Care Survey (NAMCS).
AB  - BACKGROUND: Family medicine is a specialty of breadth, providing comprehensive
      health care for the individual and the family that integrates the broad scope of
      clinical, social, and behavioral sciences. As such, the scope of practice (SOP)
      for family medicine is extensive; however, over time many family physicians
      narrow their SOP. We sought to provide a nationally representative description of
      the most common and the most critical diagnoses that family physicians see in
      their practice. METHODS: Data were extracted from the 2012 National Ambulatory
      Medical Care Survey (NAMCS) to select all ICD-9 codes reported by family
      physicians. A panel of family physicians then reviewed 1893 ICD-9 codes to place
      each code into an American Board of Family Medicine Family Medicine Certification
      Examination test plan specifications (TPS) category and provide a rating for an
      Index of Harm (IoH). RESULTS: An analysis of all 1893 ICD-9 codes seen by family
      physicians in the 2012 NAMCS found that 198 ICD-9 codes could not be assigned a
      TPS category, leaving 1695 ICD-9 codes in the dataset. Top 10 lists of ICD-9
      codes by TPS category were created for both frequency and IoH. CONCLUSIONS: This
      study provides a nationally representative description of the most common
      diagnoses that family physicians are seeing in their practice and the criticality
      of these diagnoses. These results provide insight into the domain of the
      specialty of family medicine. Medical educators may use these results to better
      tailor education and training to practice.

PMID- 29330248
TI  - The Effectiveness of Problem-Solving Therapy for Primary Care Patients'
      Depressive and/or Anxiety Disorders: A Systematic Review and Meta-Analysis.
AB  - BACKGROUND: There is increasing demand for managing depressive and/or anxiety
      disorders among primary care patients. Problem-solving therapy (PST) is a brief
      evidence- and strength-based psychotherapy that has received increasing support
      for its effectiveness in managing depression and anxiety among primary care
      patients. METHODS: We conducted a systematic review and meta-analysis of clinical
      trials examining PST for patients with depression and/or anxiety in primary care
      as identified by searches for published literature across 6 databases and manual
      searching. A weighted average of treatment effect size estimates per study was
      used for meta-analysis and moderator analysis. RESULTS: From an initial pool of
      153 primary studies, 11 studies (with 2072 participants) met inclusion criteria
      for synthesis. PST reported an overall significant treatment effect for primary
      care depression and/or anxiety (d = 0.673; P < .001). Participants' age and sex
      moderated treatment effects. Physician-involved PST in primary care, despite a
      significantly smaller treatment effect size than mental health provider only PST,
      reported an overall statistically significant effect (d = 0.35; P = .029).
      CONCLUSIONS: Results from the study supported PST's effectiveness for primary
      care depression and/or anxiety. Our preliminary results also indicated that
      physician-involved PST offers meaningful improvements for primary care patients'
      depression and/or anxiety.

PMID- 29330249
TI  - Is It Idiopathic Pulmonary Fibrosis or Not?
AB  - Pulmonary fibrosis is not uncommon. Usual interstitial pneumonitis
      (UIP)/idiopathic pulmonary fibrosis (IPF) is the most common of the idiopathic
      pulmonary fibrotic diseases and has the worst prognosis with a mean life
      expectancy of 3.8 years. The American Thoracic Society has provided guidelines
      for the accurate diagnosis of IPF.In 2014, 2 antifibrotic medications were
      approved in the United States that target the multiple fibrotic pathways of UIP,
      which increased the need for early and accurate diagnosis of IPF. The early and
      correct diagnosis is hampered by mimickers that include nonspecific interstitial
      pneumonitis, chronic hypersensitivity pneumonitis, and fibrotic sarcoidosis.
      Careful history taking, serologic testing, and Computer Tomography (CT)
      inspection can frequently make the correct diagnosis without need of invasive
      procedure. The purpose of this article is to share the most important aspects of
      the clinical and radiology presentation of IPF and its mimickers to enhance
      primary care clinician's ability to correctly and noninvasively diagnose UIP/IPF.

PMID- 29330250
TI  - The Intersection of National Immigration and Healthcare Policy.
AB  - Immigration policy and health care policy remain principal undertakings of the
      federal government. The two have recently been pursued independently in the
      judicial and legislative arenas. Unbeknownst to many policymakers, however,
      national immigration policy and health care policy are linked in ways that, if
      unattended, could undermine the well-being of a significant portion of the US
      population, specifically medically underserved rural and urban populations. Using
      current data from a workforce report of the Association of American Colleges and
      the published literature, we demonstrate the significant impact that contemporary
      immigration policy directives may have on the number and distribution of
      international medical graduates who currently provide-and by the year 2025 will
      provide-a significant portion of primary health care in the United States,
      especially in underserved small urban and rural communities.

PMID- 29330251
TI  - Diplomate Status: A Matter of Distinction.

PMID- 29330252
TI  - The Numbers Quandary in Family Medicine Obstetrics.

PMID- 29330253
TI  - Re: The Numbers Quandary in Family Medicine Obstetrics.

PMID- 29330254
TI  - Increased Levels of Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 in
      Ischemic Stroke and Transient Ischemic Attack.
AB  - BACKGROUND: Soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX
      1) has been shown to be increased in patients with acute ischemic stroke. Here,
      we evaluated plasma sLOX-1 levels and vascular carotid plaque LOX-1 (ie, OLR1)
      gene expression in patients with ischemic stroke and transient ischemic attack
      (TIA) with particular focus on their relation to time since symptom onset.
      METHODS AND RESULTS: Plasma sLOX-1 (n=232) and carotid plaque OLR1 gene
      expression (n=146) were evaluated in patients who were referred to evaluation for
      carotid endarterectomy, as well as in healthy control plasma (n=81). Patients
      were categorized according to presence of acute ischemic stroke or transient
      ischemic attack (n=35) <=7 days, >7 days <=3 months (n=90), >3 months (n=40), or
      no reported symptoms before study inclusion (n=67). Our major findings were the
      following: (1) Patients with carotid atherosclerosis had increased plasma sLOX-1
      levels as compared with controls. (2) Plaque OLR1 mRNA levels were increased in
      carotid plaques (n=146) compared with nonatherosclerotic vessels (ie, common
      iliac arteries of organ donors, n=10). (3) There were no differences in sLOX
      plasma levels or OLR1 gene expression when analyzed according to the time since
      relevant cerebral ischemic symptoms. (4) Also patients with severe carotid
      atherosclerosis without any previous ischemic events had raised sLOX-1 levels.
      (5) Immunostaining showed colocalization between LOX-1 and macrophages within the
      carotid plaques. (6) Also patients with acute stroke (within 7 days) caused by
      atrial fibrillation (n=22) had comparable raised sLOX-1 levels. CONCLUSIONS: sLOX
      1 levels are elevated in patients with ischemic stroke and transient ischemic
      attack independent of cause and time since the ischemic event.

PMID- 29330255
TI  - High-Intensity Cigarette Smoking Is Associated With Incident Diabetes Mellitus In
      Black Adults: The Jackson Heart Study.
AB  - BACKGROUND: Previous reports on whether smoking is associated with insulin
      resistance and diabetes mellitus have yielded inconsistent findings. We aimed to
      evaluate the relationship between cigarette smoking and incident diabetes
      mellitus in the Jackson Heart Study. METHODS AND RESULTS: Jackson Heart Study
      participants enrolled at baseline without prevalent diabetes mellitus (n=2991)
      were classified by self-report as current smokers, past smokers (smoked >=400
      cigarettes/life and no longer smoking), or never smokers. We quantified smoking
      intensity by number of cigarettes smoked daily; we considered >=20 cigarettes per
      day (1 pack) "high-intensity." We defined diabetes mellitus as fasting glucose
      >=126 mg/dL, hemoglobin A1c >=6.5% or International Federation of Clinical
      Chemistry units HbA1c 48 mmol/mol, or use of diabetes mellitus medication. We
      estimated the adjusted associations of smoking status, intensity, and dose (pack
      years) with incident diabetes mellitus using Poisson regression models. At
      baseline there were 361 baseline current (1-10 cigarettes per day [n=242]; >=20
      [n=119]), 502 past, and 2128 never smokers. From Visit 1 to Visit 3 (mean 8.0+/
      0.9 years), 479 participants developed incident diabetes mellitus. After
      adjustment for covariates, baseline current smokers who smoked less than a pack/d
      and past smokers had similar rates of incident diabetes mellitus compared with
      never smokers (incidence rate ratios 1.04, 95% confidence interval, 0.69-1.58 and
      1.08, 95% confidence interval, 0.82-1.42, respectively). Baseline current high
      intensity smokers had a 79% (95% confidence interval, 1.14-2.81) higher incidence
      of diabetes mellitus compared with never smokers. Smoking dose (per 10 pack
      years) was also associated with a higher incidence of diabetes mellitus
      (incidence rate ratios 1.10, 95% confidence interval, 1.03-1.19) in adjusted
      models. CONCLUSIONS: High-intensity cigarette smoking and smoking pack-years are
      associated with an increased risk of developing diabetes mellitus in blacks.

PMID- 29330256
TI  - Osteoprotegerin Is Associated With Major Bleeding But Not With Cardiovascular
      Outcomes in Patients With Acute Coronary Syndromes: Insights From the PLATO
      (Platelet Inhibition and Patient Outcomes) Trial.
AB  - BACKGROUND: Elevated levels of osteoprotegerin, a secreted tumor necrosis factor
      related molecule, might be associated with adverse outcomes in patients with
      coronary artery disease. We measured plasma osteoprotegerin concentrations on
      hospital admission, at discharge, and at 1 and 6 months after discharge in a
      predefined subset (n=5135) of patients with acute coronary syndromes in the PLATO
      (Platelet Inhibition and Patient Outcomes) trial. METHODS AND RESULTS: The
      associations between osteoprotegerin and the composite end point of
      cardiovascular death, nonprocedural spontaneous myocardial infarction or stroke,
      and non-coronary artery bypass grafting major bleeding during 1 year of follow-up
      were assessed by Cox proportional hazards models. Event rates of the composite
      end point per increasing quartile groups at baseline were 5.2%, 7.5%, 9.2%, and
      11.9%. A 50% increase in osteoprotegerin level was associated with a hazard ratio
      (HR) of 1.31 (95% confidence interval [CI], 1.21-1.42) for the composite end
      point but was not significant in adjusted analysis (ie, clinical characteristics
      and levels of C-reactive protein, troponin T, NT-proBNP [N-terminal pro-B-type
      natriuretic peptide], and growth differentiation factor-15). The corresponding
      rates of non-coronary artery bypass grafting major bleeding were 2.4%, 2.2%,
      3.8%, and 7.2%, with an unadjusted HR of 1.52 (95% CI, 1.36-1.69), and a fully
      adjusted HR of 1.26 (95% CI, 1.09-1.46). The multivariable association between
      the osteoprotegerin concentrations and the primary end point after 1 month
      resulted in an HR of 1.09 (95% CI, 0.89-1.33); for major bleeding after 1 month,
      the HR was 1.33 (95% CI, 0.91-1.96). CONCLUSIONS: In patients with acute coronary
      syndrome treated with dual antiplatelet therapy, osteoprotegerin was an
      independent marker of major bleeding but not of ischemic cardiovascular events.
      Thus, high osteoprotegerin levels may be useful in increasing awareness of
      increased bleeding risk in patients with acute coronary syndrome receiving
      antithrombotic therapy. CLINICAL TRIAL REGISTRATION: URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT00391872.

PMID- 29330257
TI  - Hemoglobin, Albuminuria, and Kidney Function in Cardiovascular Risk: The ARIC
      (Atherosclerosis Risk in Communities) Study.
AB  - BACKGROUND: Reduced estimated glomerular filtration rate (eGFR) and elevated
      urinary albumin-to-creatinine ratio (ACR) individually increase risk of
      cardiovascular disease (CVD). We hypothesized that these associations are
      stronger among people with abnormal (both low and high) hemoglobin levels.
      METHODS AND RESULTS: Using 5801 participants with available hemoglobin measures
      of the ARIC (Atherosclerosis Risk in Community) study in 1996-1998, we explored
      the cross-sectional association of eGFR and ACR with hemoglobin levels and their
      longitudinal associations with CVD (heart failure, coronary heart disease, and
      stroke) risk through 2013. At baseline, 8.8% had anemia (<13 g/dL in men and <12
      g/dL in women) and 7.2% had high hemoglobin (>=16 g/dL in men and >=15 g/dL in
      women). The adjusted prevalence ratio of anemia was 2.12 (95% confidence
      interval, 1.59-2.82) for eGFR 30 to 59 compared with >=90 mL/min per 1.73 m2 and
      1.45 (1.07-1.95) for ACR >=30 compared with <10 mg/g. ACR >=30 mg/g was also
      associated with high hemoglobin (prevalence ratio, 1.57 [1.12-2.19] compared with
      <10 mg/g). During follow-up, there were 1069 incident CVDs among 5098 CVD-free
      participants at baseline. In multivariable Cox models, lower eGFR, higher ACR,
      and anemia were each independently associated with CVD risk, with the association
      of low eGFR being slightly stronger in anemia (P-for-interaction, 0.072). There
      was no hemoglobin-ACR interaction; however, when CVD subtypes were analyzed
      separately, risk of coronary heart disease and stroke associated with high ACR
      was slightly stronger in high hemoglobin (P-for-interaction, 0.074). CONCLUSIONS:
      Kidney function, albuminuria, and anemia were correlated and independently
      associated with CVD risk. Correlation and potential interaction for
      atherosclerotic CVD between albuminuria and high hemoglobin deserve further
      investigation.

PMID- 29330259
TI  - Limited Accuracy of Administrative Data for the Identification and Classification
      of Adult Congenital Heart Disease.
AB  - BACKGROUND: Administrative data sets utilize billing codes for research and
      quality assessment. Previous data suggest that such codes can accurately identify
      adults with congenital heart disease (CHD) in the cardiology clinic, but their
      use has yet to be validated in a larger population. METHODS AND RESULTS: All
      administrative codes from an entire health system were queried for a single year.
      Adults with a CHD diagnosis code (International Classification of Diseases, Ninth
      Revision, (ICD-9) codes 745-747) defined the cohort. A previously validated
      hierarchical algorithm was used to identify diagnoses and classify patients. All
      charts were reviewed to determine a gold standard diagnosis, and comparisons were
      made to determine accuracy. Of 2399 individuals identified, 206 had no CHD by the
      algorithm or were deemed to have an uncertain diagnosis after provider review. Of
      the remaining 2193, only 1069 had a confirmed CHD diagnosis, yielding overall
      accuracy of 48.7% (95% confidence interval, 47-51%). When limited to those with
      moderate or complex disease (n=484), accuracy was 77% (95% confidence interval,
      74-81%). Among those with CHD, misclassification occurred in 23%. The
      discriminative ability of the hierarchical algorithm (C statistic: 0.79; 95%
      confidence interval, 0.77-0.80) improved further with the addition of age,
      encounter type, and provider (C statistic: 0.89; 95% confidence interval, 0.88
      0.90). CONCLUSIONS: ICD codes from an entire healthcare system were frequently
      erroneous in detecting and classifying CHD patients. Accuracy was higher for
      those with moderate or complex disease or when coupled with other data. These
      findings should be taken into account in future studies utilizing administrative
      data sets in CHD.

PMID- 29330258
TI  - Chronic Total Occlusion Percutaneous Coronary Intervention: Evidence and
      Controversies.

PMID- 29330261
TI  - Conscientious objection in abortion care.

PMID- 29330260
TI  - Race and Socioeconomic Status Independently Affect Risk of Major Amputation in
      Peripheral Artery Disease.
AB  - BACKGROUND: Black race has been shown to be a risk factor for amputation in
      peripheral artery disease (PAD); however, race has been argued to be a marker for
      socioeconomic status (SES) rather than true disparity. The aim of this study is
      to study the impact of race and SES on amputation risk in PAD patients. METHODS
      AND RESULTS: Patients with incident PAD in the national Veterans Affairs
      Corporate Data Warehouse were identified from 2003 to 2014 (N=155 647). The
      exposures were race and SES (measured by median income in residential ZIP codes).
      The outcome was incident major amputation. Black veterans were significantly more
      likely to live in low-SES neighborhoods and to present with advanced PAD. Black
      patients had a higher amputation risk in each SES stratum compared with white
      patients. In Cox models (adjusting for covariates), black race was associated
      with a 37% higher amputation risk compared with white race (hazard ratio: 1.37;
      95% confidence interval, 1.30-1.45), whereas low SES was independently predictive
      of increased risk of amputation (hazard ratio: 1.12; 95% confidence interval,
      1.06-1.17) and showed no evidence of interaction with race. In predicted
      amputation risk analysis, black race and low SES continued to be significant risk
      factors for amputation regardless of PAD presentation. CONCLUSIONS: Black race
      significantly increases the risk of amputation within the same SES stratum
      compared with white race and has an independent effect on limb loss after
      controlling for comorbidities, severity of PAD at presentation, and use of
      medications.

PMID- 29330263
TI  - Senescence-Associated Chromatin Remodeling Promotes Cancer Stemness.
AB  - Treatment-induced senescence is associated with stem-cell reprogramming of non
      stem cancer cells.

PMID- 29330262
TI  - Coffee consumption and health: umbrella review of meta-analyses of multiple
      health outcomes.

PMID- 29330264
TI  - Ependymoma Superenhancer Profiling Reveals Potential Therapeutic Targets.
AB  - Ependymoma superenhancer landscapes delineate molecular subgroups and define
      transcriptional circuitries.

PMID- 29330265
TI  - FGFR3-TACC3 Activates Mitochondrial Respiration via PIN4 Phosphorylation.
AB  - PIN4 is a FGFR3-TACC3 substrate required for ROS-mediated induction of PGCIalpha
      and tumor growth.

PMID- 29330266
TI  - HIF2alpha Antagonism Has Antitumor Activity in Advanced ccRCC.
AB  - The HIF2alpha antagonist PT2385 achieved responses in 14% of patients with
      heavily pretreated ccRCC.

PMID- 29330267
TI  - Case of acute severe postpartum urinary incontinence: an extravesical
      subsphincteric prolapsed ureterocoele.
AB  - A 32-year-old woman presents to outpatients 10 days postpartum, with symptoms of
      an intermittent vaginal lump and urinary incontinence. Vaginal examination
      revealed no demonstrable prolapse or stress incontinence. A swelling in the
      bladder was noted during an antenatal scan suggesting a ureterocoele. She was
      referred for pelvic floor physiotherapy in the first instance. Forty-eight hours
      later, she represented to casualty with discomforting vaginal lump symptoms and
      continuous urinary incontinence. At this stage on vaginal inspection, there was
      an evident dusky lump emerging from the urethra with continuous incontinence. An
      extravesical subsphincteric prolapsed ureterocoele was evident, 5 cm beyond the
      external urethral meatus. The diagnosis was confirmed with an MRI scan which
      demonstrated the prolapsed obstructing ureterocoele causing significant left
      sided hydroureteronephrosis. The ureterocoele was managed with a cystoscopy and
      transurethral incision of the ureterocoele under anaesthesia, which facilitated
      drainage and resolution. At 3-month postoperatively, the patient remains
      continent and satisfied.

PMID- 29330268
TI  - Pelvic and buttock hypoplasia reconstructed with anatomical breast implants.
AB  - Radiation therapy is used in the management of a number of childhood cancers and
      can have significant effects on skeletal growth. We present the case of a 35-year
      old woman who developed a hypoplastic pelvis and buttocks following radiotherapy
      for rhabdomyosarcoma of the vagina at the age of 2. At the age of 25, the patient
      underwent bilateral buttock augmentation with a two-stage reconstruction using
      tissue expansion followed by definitive augmentation with anatomical breast
      implant insertion. The patient continues to have a satisfactory outcome 10 years
      following reconstruction, having undergone a single uplift procedure and exchange
      of implants through the original incision 9 years postoperatively. This case
      represents a unique reconstructive challenge to plastic surgeons and was
      successfully managed with a novel approach.

PMID- 29330269
TI  - Central nervous system graft-versus-host disease (CNS-GvHD) after allogeneic
      haematopoietic stem cell transplantation.
AB  - A 60-year-old man presented with impaired consciousness and psychomotor agitation
      after a second allogeneic haematopoietic stem cell transplantation (HSCT) from a
      matched unrelated donor for acute myeloid leukaemia. Clinical, biological and
      radiological evidence suggested a diagnosis of central nervous system graft
      versus-host disease (CNS-GvHD). After intrathecal infusion of methylprednisolone,
      the clinical symptoms as well as the radiological abnormalities disappeared. The
      present report illustrates the difficulties in the diagnosis and the management
      of CNS-GvHD, a very rare and still challenging neurological complication that can
      occur after allogeneic HSCT.

PMID- 29330270
TI  - Cutis marmorata telangiectatica congenita and major lower limb asymmetry.
AB  - A 39-week-old male newborn presented at birth with atrophic erythematous and
      purpuric skin lesions, in a typical right-sided segmental distribution. Lesions
      were persistent and unaffected by rewarming in the postpartum period. Postnatal
      echocardiogram showed a predominance of the right cavities and an upper atrial
      septal defect. Cerebral and abdominal ultrasound were normal along with
      ophthalmological examination. On follow-up, lower limbs asymmetry was noted. The
      right lower limb was shorter in length and had a smaller diameter. At 6 months,
      the right lower limb was 1.5 cm shorter than the left, most likely related to
      nutritive vessels malformations. The discrepancy was even more pronounced at the
      age of 9 months. This leg-length asymmetry can lead to severe functional
      limitations in the future.

PMID- 29330271
TI  - Vitamin B12 deficiency: unusual cause of jaundice in an adolescent.
AB  - Vitamin B12 deficiency in vegans is a known cause of megaloblastic anaemia. We
      report an adolescent girl who presented with jaundice and weight loss for 6
      months secondary to vitamin B12 deficiency, leading to megaloblastic anaemia.
      Replacement with vitamin B12 reversed her symptoms, resulting in weight gain, and
      normalised her haemoglobin, red blood cell morphology, bilirubin levels and serum
      vitamin B12 levels.

PMID- 29330272
TI  - Spontaneous splenic rupture as a rare complication of G-CSF injection.
AB  - Splenic rupture is an infrequent and underdiagnosed side effect of granylocyte
      colony-stimulating factor (G-CSF). We report the case of a 54-year-old woman with
      brain and bone metastasis in a lung adenocarcinoma who was admitted for faintness
      28 days after a G-CSF injection. Abdominal CT scan confirmed the diagnosis of
      splenic rupture. A conservative treatment was chosen using a peritoneal cleansing
      during laparoscopic surgery. Clinicians should be aware of this rare toxicity as
      it could be severe, but easily reversible using appropriate surgical treatment.
      Even if prognosis remains poor for patients with lung cancer, invasive procedures
      could be considered in this rapidly evolving setting, especially in case of
      reversible adverse event.

PMID- 29330273
TI  - Rheumatoid disease: an unusual cause of relapsing meningoencephalitis.
AB  - A 73-year-old man presented with three episodes of dysphasia and disinhibited
      behaviour, a single seizure and transient ischaemic attack-like events
      characterised by right arm and/or leg weakness. These episodes were separated by
      month-long asymptomatic intervals. Medical history included rheumatoid arthritis,
      which was clinically quiescent on leflunomide.Repeated cerebrospinal fluid
      examination showed a persistent lymphocytosis with mildly reduced glucose and
      elevated protein; oligoclonal bands and viral PCR were negative. MRI of the brain
      was initially normal, but 7 months after initial presentation revealed meningeal
      enhancement with bifrontal cortical hyperintensities on T2/fluid-attenuated
      inversion recovery. Brain biopsy demonstrated necrotising granulomatous
      meningitis with mixed T cell and B cell infiltrates and without evidence of
      vasculitis or infection. Serum anticyclic citrullinated peptide antibodies were
      strongly positive.The diagnosis of rheumatoid meningoencephalitis was made on the
      basis of brain biopsy findings and serological evidence of active rheumatoid
      disease. Steroids and rituximab therapy were started leading to clinical
      stabilisation.

PMID- 29330274
TI  - Cerebrofacial arteriovenous metameric syndrome with hypopituitarism: a rare
      association.
AB  - Case of cerebrofacial arteriovenous metameric syndrome (CAMS) in a 9-year-old boy
      is described with arteriovenous malformation simultaneously involving the brain
      and face, with characteristic CAMS type 1 and 2 involvement. This patient
      demonstrates the wide spectrum of clinical manifestations of CAMS, and in this
      particular case, the patient exhibits features of hypopituitarism-an association
      that was not previously described in the literature to our knowledge. Awareness
      of the underlying embryological abnormality and recognition of resultant clinical
      and radiological presentations are paramount for diagnosis and treatment.

PMID- 29330275
TI  - Case of chest pain in a young man.
AB  - A young man with a history of smoking presented with acute-onset chest pain after
      lifting weights. He also noticed a change in his voice, tightness in his neck and
      difficulty breathing. A chest radiograph showed soft tissue emphysema in the
      neck. A CT scan of the chest revealed moderate amount of pneumomediastinum
      tracking into the neck and down to the diaphragm. He was haemodynamically stable
      and had no hypoxia or dysphagia. He was monitored for 48 hours and discharged
      home after resolution of his symptoms. A chest radiograph repeated after 6 weeks
      was normal.

PMID- 29330276
TI  - Cutaneous Mycobacterium massiliense infection from tattooing: a common yet under
      reported and persistent epidemic hazard for dermatologists.
AB  - Tattoo popularity continues to rise, with 3 in 10 Americans bearing at least one.
      Among tattoo complications, non-tuberculous mycobacteria (NTM) has emerged as a
      global public health concern. NTM infections associated with tattooing of
      immunocompetent individuals have occurred as sporadic cases and community
      outbreaks. Water sources are considered the major pathogenic reservoirs. Tattoo
      related inoculation has been linked to contamination of ink, either during the
      manufacturing process or during dilution of black ink using non-sterile water.
      NTM infections have also been documented in a number of cosmetic and surgical
      procedures, including cutaneous surgery, Mohs micrographic surgery, mesotherapy,
      liposuction and laser resurfacing. NTM inoculation through exposure to
      contaminated water or non-sterile instruments remains a challenge for
      dermatologists and risk to patients. We reported a case of cutaneous
      Mycobacterium massiliense infection following tattoo placement. This report
      underscores the importance of clinicians to consider NTM infections in the
      differential diagnosis of procedure-related reactions.

PMID- 29330277
TI  - Bancroftian filariasis associated with male sterility.

PMID- 29330278
TI  - Multiple cranial nerve palsies secondary to a recurrence of Hansen's disease.

PMID- 29330279
TI  - Rare cause of isolated severe coagulation failure in cirrhosis: traditional
      healing with fenugreek.
AB  - Patients with cirrhosis develop decompensation events during the natural history
      of the disease that encompass ascites, variceal bleeding, hepatic encephalopathy
      and jaundice. Coagulation failure, defined using the international normalised
      ratio, even though not a decompensation event, is important in patients with
      stratifying cirrhosis into those who require liver transplantation for long-term
      survival. Isolated coagulation failure in cirrhosis is rare and usually occurs
      with use of anticoagulants in the setting of vascular diseases. We reported the
      case of a patient with compensated cirrhosis in whom, isolated severe coagulation
      failure was found to be due to excessive use of fenugreek milk porridge as part
      of traditional healing. The coagulation failure was promptly reversed with
      avoidance of fenugreek and supplementation with vitamin K.

PMID- 29330280
TI  - Cutaneous larva migrans with pulmonary involvement.

PMID- 29330281
TI  - Hepatic portal venous gas after diving.

PMID- 29330282
TI  - Population-dependent Intron Retention and DNA Methylation in Breast Cancer.
AB  - Regulation of gene expression by DNA methylation in gene promoter regions is well
      studied; however, the effects of methylation in the gene body (exons and introns)
      on gene expression are comparatively understudied. Recently, hypermethylation has
      been implicated in the inclusion of alternatively spliced exons; moreover, exon
      recognition can be enhanced by recruiting the methyl-CpG-binding protein (MeCP2)
      to hypermethylated sites. This study examines whether the methylation status of
      an intron is correlated with how frequently the intron is retained during
      splicing using DNA methylation and RNA sequencing data from breast cancer tissue
      specimens in The Cancer Genome Atlas. Interestingly, hypomethylation of introns
      is correlated with higher levels of intron expression in mRNA and the methylation
      level of an intron is inversely correlated with its retention in mRNA from the
      gene in which it is located. Furthermore, significant population differences were
      observed in the methylation level of retained introns. In African-American
      donors, retained introns were not only less methylated compared to European
      American donors, but also were more highly expressed. This underscores the need
      for understanding epigenetic differences in populations and their correlation
      with breast cancer is an important step toward achieving personalized cancer
      care.Implications: This research contributes to the understanding of how
      epigenetic markers in the gene body communicate with the transcriptional
      machinery to control transcript diversity and differential biological response to
      changes in methylation status could underlie some of the known, yet unexplained,
      disparities in certain breast cancer patient populations. Mol Cancer Res; 16(3);
      461-9. (c)2018 AACR.

PMID- 29330284
TI  - Novel Intergenically Spliced Chimera, NFATC3-PLA2G15, Is Associated with
      Aggressive T-ALL Biology and Outcome.
AB  - Leukemias are frequently characterized by the expression of oncogenic fusion
      chimeras that normally arise due to chromosomal rearrangements. Intergenically
      spliced chimeric RNAs (ISC) are transcribed in the absence of structural genomic
      changes, and aberrant ISC expression is now recognized as a potential driver of
      cancer. To better understand these potential oncogenic drivers, high-throughput
      RNA sequencing was performed on T-acute lymphoblastic leukemia (T-ALL) patient
      specimens (n = 24), and candidate T-ALL-related ISCs were identified (n = 55; a
      median of 4/patient). In-depth characterization of the NFATC3-PLA2G15 chimera,
      which was variably expressed in primary T-ALL, was performed. Functional
      assessment revealed that the fusion had lower activity than wild-type NFATC3 in
      vitro, and T-ALLs with elevated NFATC3-PLA2G15 levels had reduced transcription
      of canonical NFAT pathway genes in vivo Strikingly, high expression of the NFATC3
      PLA2G15 chimera correlated with aggressive disease biology in murine patient
      derived T-ALL xenografts, and poor prognosis in human T-ALL patients. Mol Cancer
      Res; 16(3); 470-5. (c)2018 AACR.

PMID- 29330283
TI  - Centriole Overduplication is the Predominant Mechanism Leading to Centrosome
      Amplification in Melanoma.
AB  - Centrosome amplification (CA) is common in cancer and can arise by centriole
      overduplication or by cell doubling events, including the failure of cell
      division and cell-cell fusion. To assess the relative contributions of these two
      mechanisms, the number of centrosomes with mature/mother centrioles was examined
      by immunofluorescence in a tissue microarray of human melanomas and benign nevi
      (n = 79 and 17, respectively). The centrosomal protein 170 (CEP170) was used to
      identify centrosomes with mature centrioles; this is expected to be present in
      most centrosomes with cell doubling, but on fewer centrosomes with
      overduplication. Using this method, it was determined that the majority of CA in
      melanoma can be attributed to centriole overduplication rather than cell doubling
      events. As Polo-like kinase 4 (PLK4) is the master regulator of centriole
      duplication, the hypothesis that PLK4 overexpression contributes to centriole
      overduplication was evaluated. PLK4 is significantly overexpressed in melanoma
      compared with benign nevi and in a panel of human melanoma cell lines (A375,
      Hs294T, G361, WM35, WM115, 451Lu, and SK-MEL-28) compared with normal human
      melanocytes. Interestingly, although PLK4 expression did not correlate with CA in
      most cases, treatment of melanoma cells with a selective small-molecule PLK4
      inhibitor (centrinone B) significantly decreased cell proliferation. The
      antiproliferative effects of centrinone B were also accompanied by induction of
      apoptosis.Implications: This study demonstrates that centriole overduplication is
      the predominant mechanism leading to centrosome amplification in melanoma and
      that PLK4 should be further evaluated as a potential therapeutic target for
      melanoma treatment. Mol Cancer Res; 16(3); 517-27. (c)2018 AACR.

PMID- 29330285
TI  - Foxo-dependent Par-4 Upregulation Prevents Long-term Survival of Residual Cells
      Following PI3K-Akt Inhibition.
AB  - Tumor recurrence is a leading cause of death and is thought to arise from a
      population of residual cells that survive treatment. These residual cancer cells
      can persist, locally or at distant sites, for years or decades. Therefore,
      understanding the pathways that regulate residual cancer cell survival may
      suggest opportunities for targeting these cells to prevent recurrence.
      Previously, it was observed that the proapoptotic protein (PAWR/Par-4) negatively
      regulates residual cell survival and recurrence in mice and humans. However, the
      mechanistic underpinnings on how Par-4 expression is regulated are unclear. Here,
      it is demonstrated that Par-4 is transcriptionally upregulated following
      treatment with multiple drugs targeting the PI3K-Akt-mTOR signaling pathway, and
      identify the Forkhead family of transcription factors as mediators of this
      upregulation. Mechanistically, Foxo3a directly binds to the Par-4 promoter and
      activates its transcription following inhibition of the PI3K-Akt pathway. This
      Foxo-dependent Par-4 upregulation limits the long-term survival of residual cells
      following treatment with therapeutics that target the PI3K-Akt pathway. Taken
      together, these results indicate that residual breast cancer tumor cell survival
      and recurrence requires circumventing Foxo-driven Par-4 upregulation and suggest
      that approaches to enforce Par-4 expression may prevent residual cell survival
      and recurrence. Mol Cancer Res; 16(4); 599-609. (c)2018 AACR.

PMID- 29330287
TI  - Targeted AKT Inhibition in Prostate Cancer Cells and Spheroids Reduces Aerobic
      Glycolysis and Generation of Hyperpolarized [1-13C] Lactate.
AB  - The PI3K/AKT/mTOR (PAM) signaling pathway is frequently mutated in prostate
      cancer. Specific AKT inhibitors are now in advanced clinical trials, and this
      study investigates the effect of MK2206, a non-ATP-competitive inhibitor, on the
      cellular metabolism of prostate cancer cells. We observed a reduction in cell
      motility and aerobic glycolysis in prostate cancer cells with treatment. These
      changes were not accompanied by a reduction in the ratio of high-energy
      phosphates or a change in total protein levels of enzymes and transporters
      involved in glycolysis. However, a decreased ratio of NAD+/NADH was observed,
      motivating the use of hyperpolarized magnetic resonance spectroscopy (HP-MRS) to
      detect treatment response. Spectroscopic experiments were performed on tumor
      spheroids, 3D structures that self-organize in the presence of an extracellular
      matrix. Treated spheroids showed decreased lactate production with on-target
      inhibition confirmed using IHC, demonstrating that HP-MRS can be used to probe
      treatment response in prostate cancer spheroids and can provide a biomarker for
      treatment response. Mol Cancer Res; 16(3); 453-60. (c)2018 AACR.

PMID- 29330286
TI  - Agonist-induced CXCR4 and CB2 Heterodimerization Inhibits Galpha13/RhoA-mediated
      Migration.
AB  - G-protein-coupled receptor (GPCR) heterodimerization has emerged as a means by
      which alternative signaling entities can be created; yet, how receptor
      heterodimers affect receptor pharmacology remains unknown. Previous observations
      suggested a biochemical antagonism between GPCRs, CXCR4 and CB2 (CNR2), where
      agonist-bound CXCR4 and agonist-bound CB2 formed a physiologically nonfunctional
      heterodimer on the membrane of cancer cells, inhibiting their metastatic
      potential in vitro However, the reduced signaling entities responsible for the
      observed functional outputs remain elusive. This study now delineates the
      signaling mechanism whereby heterodimeric association between CXCR4 and CB2,
      induced by simultaneous agonist treatment, results in decreased CXCR4-mediated
      cell migration, invasion, and adhesion through inhibition of the Galpha13/RhoA
      signaling axis. Activation of CXCR4 by its cognate ligand, CXCL12, stimulates
      Galpha13 (GNA13), and subsequently, the small GTPase RhoA, which is required for
      directional cell migration and the metastatic potential of cancer cells. These
      studies in prostate cancer cells demonstrate decreased protein expression levels
      of Galpha13 and RhoA upon simultaneous CXCR4/CB2 agonist stimulation.
      Furthermore, the agonist-induced heterodimer abrogated RhoA-mediated cytoskeletal
      rearrangement resulting in the attenuation of cell migration and invasion of an
      endothelial cell barrier. Finally, a reduction was observed in the expression of
      integrin alpha5 (ITGA5) upon heterodimerization, supported by decreased cell
      adhesion to extracellular matrices in vitro Taken together, the data identify a
      novel pharmacologic mechanism for the modulation of tumor cell migration and
      invasion in the context of metastatic disease.Implications: This study
      investigates a signaling mechanism by which GPCR heterodimerization inhibits
      cancer cell migration. Mol Cancer Res; 16(4); 728-39. (c)2018 AACR.

PMID- 29330288
TI  - Epigenetically Regulated Chromosome 14q32 miRNA Cluster Induces Metastasis and
      Predicts Poor Prognosis in Lung Adenocarcinoma Patients.
AB  - Most lung cancer deaths are related to metastases, which indicates the necessity
      of detecting and inhibiting tumor cell dissemination. Here, we aimed to identify
      miRNAs involved in metastasis of lung adenocarcinoma as prognostic biomarkers and
      therapeutic targets. To that end, lymph node metastasis-associated miRNAs were
      identified in The Cancer Genome Atlas lung adenocarcinoma patient cohort
      (sequencing data; n = 449) and subsequently validated by qRT-PCR in an
      independent clinical cohort (n = 108). Overexpression of miRNAs located on
      chromosome 14q32 was associated with metastasis in lung adenocarcinoma patients.
      Importantly, Kaplan-Meier analysis and log-rank test revealed that higher
      expression levels of individual 14q32 miRNAs (mir-539, mir-323b, and mir-487a)
      associated with worse disease-free survival of never-smoker patients. Epigenetic
      analysis including DNA methylation microarray data and bisulfite sequencing
      validation demonstrated that the induction of 14q32 cluster correlated with
      genomic hypomethylation of the 14q32 locus. CRISPR activation technology, applied
      for the first time to functionally study the increase of clustered miRNA levels
      in a coordinated manner, showed that simultaneous overexpression of 14q32 miRNAs
      promoted tumor cell migratory and invasive properties. Analysis of individual
      miRNAs by mimic transfection further illustrated that miR-323b-3p, miR-487a-3p,
      and miR-539-5p significantly contributed to the invasive phenotype through the
      indirect regulation of different target genes. In conclusion, overexpression of
      14q32 miRNAs, associated with the respective genomic hypomethylation, promotes
      metastasis and correlates with poor patient prognosis in lung
      adenocarcinoma.Implications: This study points to chromosome 14q32 miRNAs as
      promising targets to inhibit tumor cell dissemination and to predict patient
      prognosis in lung adenocarcinoma. Mol Cancer Res; 16(3); 390-402. (c)2018 AACR.

PMID- 29330289
TI  - BRCA1 through Its E3 Ligase Activity Regulates the Transcription Factor Oct1 and
      Carbohydrate Metabolism.
AB  - The tumor suppressor BRCA1 regulates the DNA damage response (DDR) and other
      processes that remain incompletely defined. Among these, BRCA1 heterodimerizes
      with BARD1 to ubiquitylate targets via its N-terminal E3 ligase activity. Here,
      it is demonstrated that BRCA1 promotes oxidative metabolism by degrading Oct1
      (POU2F1), a transcription factor with proglycolytic and tumorigenic effects.
      BRCA1 E3 ubiquitin ligase mutation skews cells toward a glycolytic metabolic
      profile while elevating Oct1 protein. CRISPR-mediated Oct1 deletion reverts the
      glycolytic phenotype. RNA sequencing (RNAseq) confirms deregulation of metabolic
      genes downstream of Oct1. BRCA1 mediates Oct1 ubiquitylation and degradation, and
      mutation of two ubiquitylated Oct1 lysines insulates the protein against BRCA1
      mediated destabilization. Oct1 deletion in MCF-7 breast cancer cells does not
      perturb growth in standard culture, but inhibits growth in soft agar and
      xenograft assays. In primary breast cancer clinical specimens, Oct1 protein
      levels correlate positively with tumor aggressiveness and inversely with BRCA1.
      These results identify BRCA1 as an Oct1 ubiquitin ligase that catalyzes Oct1
      degradation to promote oxidative metabolism and restrict tumorigenicity. Mol
      Cancer Res; 16(3); 439-52. (c)2018 AACR.

PMID- 29330290
TI  - Dual Inhibition of CDK4 and CDK2 via Targeting p27 Tyrosine Phosphorylation
      Induces a Potent and Durable Response in Breast Cancer Cells.
AB  - Cyclin-dependent kinase 4/6 (CDK4/6)-specific inhibitors, such as palbociclib,
      have shown clinical efficacy, but primary or secondary resistance has emerged as
      a problem. To develop more effective therapeutic approaches, investigation is
      needed into the mechanisms of resistance or adaption. Here, it is demonstrated
      that CDK2 compensates for loss of CDK4 activity to rescue palbociclib-arrested
      breast cancer cells, suggesting that inhibition of both kinases is required to
      achieve durable response. In addition, a novel strategy is described to inhibit
      tyrosine phosphorylation of p27Kip1 (CDKN1B) and simultaneously inhibit both CDK2
      and CDK4. p27Kip1 is a required assembly factor for cyclin-CDK4 complexes, but it
      must be phosphorylated on residue Y88 to open or activate the complex. The Brk
      SH3 peptide, ALT, blocks p27 Y88 phosphorylation, inhibiting CDK4.
      Nonphosphorylated p27 is no longer a target for ubiquitin-mediated degradation
      and this stabilized p27 now also inhibits CDK2 activity. Thus, ALT induction
      inhibits both the kinase that drives proliferation (CDK4) and the kinase that
      mediates resistance (CDK2), causing a potent and long-lasting cell-cycle arrest.
      ALT arrests growth of all breast cancer subgroups and synergizes with palbociclib
      to increase cellular senescence and to cause tumor regression in breast cancer
      xenograft models. The use of ALT demonstrates that both CDK4 and CDK2 need to be
      inhibited if long-term efficacy is to be achieved and represents a novel modality
      to inhibit breast cancer cells.Implications: Modulating tyrosine phosphorylation
      of p27 impacts both proliferative (CDK4) and resistance (CDK2) mechanisms in
      breast cancer and suggests that phospho-p27 status may serve as a biomarker for
      patients that are responsive to CDK4/6 inhibition. Mol Cancer Res; 16(3); 361-77.
      (c)2018 AACR.

PMID- 29330291
TI  - Keap1 Inhibits Metastatic Properties of NSCLC Cells by Stabilizing Architectures
      of F-Actin and Focal Adhesions.
AB  - Low expression of the tumor suppressor Kelch-like ECH-associated protein 1
      (KEAP1) in non-small cell lung cancer (NSCLC) often results in higher malignant
      biological behavior and poor prognosis; however, the underlying mechanism remains
      unclear. The present study demonstrates that overexpression of Keap1
      significantly suppresses migration and invasion of three different lung cancer
      cells (A549, H460, and H1299). Highly expressed Keap1, compared with the control,
      promotes formation of multiple stress fibers with larger mature focal adhesion
      complexes in the cytoplasm where only fine focal adhesions were observed in the
      membrane under control conditions. RhoA activity significantly increased when
      Keap1 was overexpressed, whereas Myosin 9b expression was reduced but could be
      rescued by proteasome inhibition. Noticeably, mouse tumor xenografts with Keap1
      overexpression were smaller in size and less metastatic relative to the control
      group. Taken together, these results demonstrate that Keap1 stabilizes F-actin
      cytoskeleton structures and inhibits focal adhesion turnover, thereby restraining
      the migration and invasion of NSCLC. Therefore, increasing Keap1 or targeting its
      downstream molecules might provide potential therapeutic benefits for the
      treatment of patients with NSCLC.Implications: This study provides mechanistic
      insight on the metastatic process in NSCLC and suggests that Keap1 and its
      downstream molecules may be valuable drug targets for NSCLC patients. Mol Cancer
      Res; 16(3); 508-16. (c)2018 AACR.

PMID- 29330292
TI  - Microenvironment-Derived Regulation of HIF Signaling Drives Transcriptional
      Heterogeneity in Glioblastoma Multiforme.
AB  - The evolving and highly heterogeneous nature of malignant brain tumors underlies
      their limited response to therapy and poor prognosis. In addition to genetic
      alterations, highly dynamic processes, such as transcriptional and metabolic
      reprogramming, play an important role in the development of tumor heterogeneity.
      The current study reports an adaptive mechanism in which the metabolic
      environment of malignant glioma drives transcriptional reprogramming.
      Multiregional analysis of a glioblastoma patient biopsy revealed a metabolic
      landscape marked by varying stages of hypoxia and creatine enrichment. Creatine
      treatment and metabolism was further shown to promote a synergistic effect
      through upregulation of the glycine cleavage system and chemical regulation of
      prolyl-hydroxylase domain. Consequently, creatine maintained a reduction of
      reactive oxygen species and change of the alpha-ketoglutarate/succinate ratio,
      leading to an inhibition of HIF signaling in primary tumor cell lines. These
      effects shifted the transcriptional pattern toward a proneural subtype and
      reduced the rate of cell migration and invasion in vitroImplications:
      Transcriptional subclasses of glioblastoma multiforme are heterogeneously
      distributed within the same tumor. This study uncovered a regulatory function of
      the tumor microenvironment by metabolism-driven transcriptional reprogramming in
      infiltrating glioma cells. Mol Cancer Res; 16(4); 655-68. (c)2018 AACR.

PMID- 29330294
TI  - Establishment of the First Well-differentiated Human Pancreatic Neuroendocrine
      Tumor Model.
AB  - Clinical options for systemic therapy of neuroendocrine tumors (NET) are limited.
      Development of new drugs requires suitable representative in vitro and in vivo
      model systems. So far, the unavailability of a human model with a well
      differentiated phenotype and typical growth characteristics has impaired
      preclinical research in NET. Herein, we establish and characterize a lymph node
      derived cell line (NT-3) from a male patient with well-differentiated pancreatic
      NET. Neuroendocrine differentiation and tumor biology was compared with existing
      NET cell lines BON and QGP-1. In vivo growth was assessed in a xenograft mouse
      model. The neuroendocrine identity of NT-3 was verified by expression of multiple
      NET-specific markers, which were highly expressed in NT-3 compared with BON and
      QGP-1. In addition, NT-3 expressed and secreted insulin. Until now, this well
      differentiated phenotype is stable since 58 passages. The proliferative labeling
      index, measured by Ki-67, of 14.6% +/- 1.0% in NT-3 is akin to the original tumor
      (15%-20%), and was lower than in BON (80.6% +/- 3.3%) and QGP-1 (82.6% +/- 1.0%).
      NT-3 highly expressed somatostatin receptors (SSTRs: 1, 2, 3, and 5). Upon
      subcutaneous transplantation of NT-3 cells, recipient mice developed tumors with
      an efficient tumor take rate (94%) and growth rate (139% +/- 13%) by 4 weeks.
      Importantly, morphology and neuroendocrine marker expression of xenograft tumors
      resembled the original human tumor.Implications: High expression of somatostatin
      receptors and a well-differentiated phenotype as well as a slow growth rate
      qualify the new cell line as a relevant model to study neuroendocrine tumor
      biology and to develop new tumor treatments. Mol Cancer Res; 16(3); 496-507.
      (c)2018 AACR.

PMID- 29330295
TI  - Epigenetic Reprogramming of Pericentromeric Satellite DNA in Premalignant and
      Malignant Lesions.
AB  - Repression of repetitive DNA is important for maintaining genomic stability, but
      is often perturbed in cancer. For instance, the megabase satellite domain at
      chromosome 1q12 is a common site of genetic rearrangements, such as
      translocations and deletions. Polycomb-group proteins can be observed as large
      subnuclear domains called polycomb bodies, the composition and cellular function
      of which has remained elusive. This study demonstrates that polycomb bodies are
      canonical subunits of the multiprotein polycomb repressive complex 1 deposited on
      1q12 pericentromeric satellite DNA, which are normally maintained as constitutive
      heterochromatin by other mechanisms. Furthermore, the data reveal that polycomb
      bodies are exclusive to premalignant and malignant cells, being absent in normal
      cells. For instance, polycomb bodies are present in melanocytic cells of nevi and
      conserved in primary and metastatic melanomas. Deposition of polycomb on the 1q12
      satellite DNA in melanoma development correlated with reduced DNA methylation
      levels. In agreement with this, inhibition of DNA methyltransferases, with the
      hypomethylating agent guadecitabine (SGI-110), was sufficient for polycomb body
      formation on pericentromeric satellites in primary melanocytes. This suggests
      that polycomb bodies form in cancer cells with global DNA demethylation to
      control the stability of pericentromeric satellite DNA. These results reveal a
      novel epigenetic perturbation specific to premalignant and malignant cells that
      may be used as an early diagnostic marker for detection of precancerous changes
      and a new therapeutic entry point.Implications: Pericentromeric satellite DNA is
      epigenetically reprogrammed into polycomb bodies as a premalignant event with
      implications for transcriptional activity and genomic stability. Mol Cancer Res;
      16(3); 417-27. (c)2018 AACR.

PMID- 29330293
TI  - Differential Regulation of LET-7 by LIN28B Isoform-Specific Functions.
AB  - The RNA-binding protein LIN28B plays an important role in development, stem cell
      biology, and tumorigenesis. LIN28B has two isoforms: the LIN28B-long and -short
      isoforms. Although studies have revealed the functions of the LIN28B-long isoform
      in tumorigenesis, the role of the LIN28B-short isoform remains unclear and
      represents a major gap in the field. The LIN28B-long and -short isoforms are
      expressed in a subset of human colorectal cancers and adjacent normal colonic
      mucosa, respectively. To elucidate the functional and mechanistic aspects of
      these isoforms, colorectal cancer cells (Caco-2 and LoVo) were generated to
      either express no LIN28B or the -short or -long isoform. Interestingly, the long
      isoform suppressed LET-7 expression and activated canonical RAS/ERK signaling,
      whereas the short isoform did not. The LIN28B-long isoform-expressing cells
      demonstrated increased drug resistance to 5-fluorouracil and cisplatin through
      the upregulation of ERCC1, a DNA repair gene, in a LET-7-dependent manner. The
      LIN28B-short isoform preserved its ability to bind pre-let-7, without inhibiting
      the maturation of LET-7, and competed with the LIN28B-long isoform for binding to
      pre-let-7 Coexpression of the short isoform in the LIN28B-long isoform-expressing
      cells rescued the phenotypes induced by the LIN28B-long isoform.Implications:
      This study demonstrates the differential antagonistic functions of the LIN28B
      short isoform against the LIN28B-long isoform through an inability to degrade LET
      7, which leads to the novel premise that the short isoform may serve to
      counterbalance the long isoform during normal colonic epithelial homeostasis, but
      its downregulation during colonic carcinogenesis may reveal the protumorigenic
      effects of the long isoform. Mol Cancer Res; 16(3); 403-16. (c)2018 AACR.

PMID- 29330296
TI  - Tumor Progression Is Mediated by Thymosin-beta4 through a TGFbeta/MRTF Signaling
      Axis.
AB  - Although enhanced thymosin beta4 (TMSB4X/Tbeta4) expression is associated with
      tumor progression and metastasis, its tumor-promoting functions remain largely
      unknown. Here, it is demonstrated that TGFbeta facilitates Tbeta4 expression and
      leads to the activation of myocardin-related transcription factors (MRTF), which
      are coactivators of serum response factor (SRF) and regulate the expression of
      genes critical for the epithelial-mesenchymal transition (EMT) and tumor
      metastasis. In murine mammary gland cells (NMuMG), Tbeta4 upregulation is
      required for full induction of a MRTF-regulated EMT gene expression program after
      TGFbeta stimulation. Tbeta4 levels are transcriptionally regulated via the novel
      cis-acting element AGACAAAG, which interacts with Smad and T-cell factor/lymphoid
      enhancer factor (TCF/LEF) to synergistically activate the Tbeta4 promoter
      downstream of TGFbeta. Murine skin melanoma cells (B16F0 and B16F1) also show the
      expression regulation of Tbeta4 by Smad and TCF/LEF. Tbeta4-knockout B16F1
      (Tbeta4 KO) clones show significantly diminished expression level of tumor
      associated genes, which is regulated by the TGFbeta/MRTFs pathway. In multiple
      human cancers, Tbeta4 levels correlate positively with TGFbeta1 and the tumor
      associated gene expression levels through processes that respectively depend on
      TGFbeta receptor 1 (TGFBR1) and MRTF expression. Kaplan-Meier survival analyses
      demonstrate that high Tbeta4 expression associates with poor prognosis in an SRF
      expression-dependent manner in several cancers. In mice, Tbeta4 KO clones show
      significantly decreased experimental metastatic potential; furthermore, ectopic
      expression of constitutively active MRTF-A fully restores the diminished
      metastatic activity. In conclusion, the TGFbeta/Tbeta4/MRTF/SRF pathway is
      critical for metastasis and tumor progression.Implications: These findings define
      a molecular mechanism underlying a tumor-promoting function of thymosin beta4
      through activation of MRTF/SRF signaling. Mol Cancer Res; 16(5); 880-93. (c)2018
      AACR.

PMID- 29330298
TI  - Stemness Is Enhanced in Gastric Cancer by a SET/PP2A/E2F1 Axis.
AB  - Gastric cancer is the fifth most common malignancy and the third leading cause of
      cancer-related deaths worldwide. Chemotherapies against gastric cancer often
      fail, with cancer recurrence due potentially to the persistence of cancer stem
      cells. This unique subpopulation of cells in tumors possesses the ability to self
      renew and dedifferentiate. These cancer stem cells are critical for initiation,
      maintenance, metastasis, and relapse of cancers; however, the molecular
      mechanisms supporting cancer stemness remain largely unknown. Increased kinase
      and decreased phosphatase activity are hallmarks of oncogenic signaling. Protein
      phosphatase 2A (PP2A) functions as a tumor-suppressor enzyme, and elevated levels
      of SET/I2PP2A, an endogenous PP2A protein inhibitor, are correlated with poor
      prognosis of several human cancers. Here, it was determined that SET expression
      was elevated in tumor tissue in a gastric cancer mouse model system, and SET
      expression was positively correlated with poor survival of human gastric cancer
      patients. Mechanistically, SET knockdown decreased E2F1 levels and suppressed the
      stemness of cancer cell lines. Immunoprecipitations show SET associated with the
      PP2A-B56 complex, and the B56 subunit interacted with the E2F1 transcription
      factor. Treatment of gastric cancer cells with the SET-targeting drug OP449
      increased PP2A activity, decreased E2F1 protein levels, and suppressed stemness
      of cancer cells. These data indicate that a SET/PP2A/E2F1 axis regulates cancer
      cell stemness and is a potential target for gastric cancer therapy.Implications:
      This study highlights the oncogenic role of SET/I2PP2A in gastric cancer and
      suggests that SET maintains cancer cell stemness by suppressing PP2A activity and
      stabilizing E2F1. Mol Cancer Res; 16(3); 554-63. (c)2018 AACR.

PMID- 29330297
TI  - Characterization and Evidence of the miR-888 Cluster as a Novel Cancer Network in
      Prostate.
AB  - Prostate cancer afflicts 1 in 7 men and is the second leading cause of male
      cancer-related deaths in the United States. MicroRNAs (miRNAs), an extensive
      class of approximately 22 nucleotide noncoding RNAs, are often aberrantly
      expressed in tissues and fluids from prostate cancer patients, but the mechanisms
      of how specific miRNAs regulate prostate tumorigenesis and metastasis are poorly
      understood. Here, miR-888 was identified as a novel prostate factor that promotes
      proliferation and migration. miR-888 resides within a genomic cluster of 7 miRNA
      genes (mir-892c, mir-890, mir-888, mir-892a, mir-892b, mir-891b, mir-891a) on
      human chromosome Xq27.3. Moreover, as miR-888 maps within HPCX1, a locus
      associated with susceptibility and/or hereditary prostate cancer, it was
      hypothesized that additional miRNA cluster members also play functional roles in
      the prostate. Expression analysis determined that cluster members were similarly
      elevated in metastatic PC3-ML prostate cells and their secreted exosomes, as well
      as enriched in expressed prostatic secretions urine-derived exosomes obtained
      from clinical patients with high-grade prostate cancer. In vitro assays revealed
      that miR-888 cluster members selectively modulated PC3-derived and LNCaP cell
      proliferation, migration, invasion, and colony formation. Mouse xenograft studies
      verified miR-888 and miR-891a as pro-oncogenic factors that increased prostate
      tumor growth in vivo Further analysis validated RBL1, KLF5, SMAD4, and TIMP2 as
      direct miR-888 targets and that TIMP2 is also coregulated by miR-891a. This study
      provides the first comprehensive analysis of the entire miR-888 cluster and
      reveals biological insight.Implications: This work reveals a complex noncoding
      RNA network in the prostate that could be developed as effective diagnostic and
      therapeutic tools for advanced prostate cancer. Mol Cancer Res; 16(4); 669-81.
      (c)2018 AACR.

PMID- 29330299
TI  - Effects of allelic variations in the human myxovirus resistance protein A on its
      antiviral activity.
AB  - Only a minority of patients infected with seasonal influenza A viruses exhibit a
      severe or fatal outcome of infection, but the reasons for this inter-individual
      variability in influenza susceptibility are unclear. To gain further insights
      into the molecular mechanisms underlying this variability, we investigated
      naturally occurring allelic variations of the myxovirus resistance 1 (MX1) gene
      coding for the influenza restriction factor MxA. The interferon-induced dynamin
      like GTPase consists of an N-terminal GTPase domain, a bundle signaling element,
      and a C-terminal stalk responsible for oligomerization and viral target
      recognition. We used online databases to search for variations in the MX1 gene.
      Deploying in vitro approaches, we found that non-synonymous variations in the
      GTPase domain cause the loss of antiviral and enzymatic activities. Furthermore,
      we showed that these amino acid substitutions disrupt the interface for GTPase
      domain dimerization required for the stimulation of GTP hydrolysis. Variations in
      the stalk were neutral or slightly enhanced or abolished MxA antiviral function.
      Remarkably, two other stalk variants altered MxA's antiviral specificity.
      Variations causing the loss of antiviral activity were found only in heterozygous
      carriers. Interestingly, the inactive stalk variants blocked the antiviral
      activity of WT MxA in a dominant-negative way, suggesting that heterozygotes are
      phenotypically MxA-negative. In contrast, the GTPase-deficient variants showed no
      dominant-negative effect, indicating that heterozygous carriers should remain
      unaffected. Our results demonstrate that naturally occurring mutations in the
      human MX1 gene can influence MxA function, which may explain individual
      variations in influenza virus susceptibility in the human population.

PMID- 29330300
TI  - Real-time imaging of yeast cells reveals several distinct mechanisms of curing of
      the [URE3] prion.
AB  - The [URE3] yeast prion is the self-propagating amyloid form of the Ure2 protein.
      [URE3] is cured by overexpression of several yeast proteins, including Ydj1,
      Btn2, Cur1, Hsp42, and human DnaJB6. To better understand [URE3] curing, we used
      real-time imaging with a yeast strain expressing a GFP-labeled full-length Ure2
      construct to monitor the curing of [URE3] over time. [URE3] yeast cells exhibited
      numerous fluorescent foci, and expression of the GFP-labeled Ure2 affected
      neither mitotic stability of [URE3] nor the rate of [URE3] curing by the curing
      proteins. Using guanidine to cure [URE3] via Hsp104 inactivation, we found that
      the fluorescent foci are progressively lost as the cells divide until they are
      cured; the fraction of cells that retained the foci was equivalent to the [URE3]
      cell fraction measured by a plating assay, indicating that the foci were the
      prion seeds. During the curing of [URE3] by Btn2, Cur1, Hsp42, or Ydj1
      overexpression, the foci formed aggregates, many of which were 0.5 MUm or greater
      in size, and [URE3] was cured by asymmetric segregation of the aggregated seeds.
      In contrast, DnaJB6 overexpression first caused a loss of detectable foci in
      cells that were still [URE3] before there was complete dissolution of the seeds,
      and the cells were cured. We conclude that GFP labeling of full-length Ure2
      enables differentiation among the different [URE3]-curing mechanisms, including
      inhibition of severing followed by seed dilution, seed clumping followed by
      asymmetric segregation between mother and daughter cells, and seed dissolution.

PMID- 29330301
TI  - Genetic control of predominantly error-free replication through an acrolein
      derived minor-groove DNA adduct.
AB  - Acrolein, an alpha,beta-unsaturated aldehyde, is generated in vivo as the end
      product of lipid peroxidation and from metabolic oxidation of polyamines, and it
      is a ubiquitous environmental pollutant. The reaction of acrolein with the N2 of
      guanine in DNA leads to the formation of gamma-hydroxy-1-N2-propano-2'
      deoxyguanosine (gamma-HOPdG), which can exist in DNA in a ring-closed or a ring
      opened form. Here, we identified the translesion synthesis (TLS) DNA polymerases
      (Pols) that conduct replication through the permanently ring-opened reduced form
      of gamma-HOPdG ((r) gamma-HOPdG) and show that replication through this adduct is
      mediated via Rev1/Poleta-, Poliota/Polkappa-, and Poltheta-dependent pathways,
      respectively. Based on biochemical and structural studies, we propose a role for
      Rev1 and Poliota in inserting a nucleotide (nt) opposite the adduct and for Pols
      eta and kappa in extending synthesis from the inserted nt in the respective TLS
      pathway. Based on genetic analyses and biochemical studies with Poltheta, we
      infer a role for Poltheta at both the nt insertion and extension steps of TLS.
      Whereas purified Rev1 and Poltheta primarily incorporate a C opposite (r) gamma
      HOPdG, Poliota incorporates a C or a T opposite the adduct; nevertheless, TLS
      mediated by the Poliota-dependent pathway as well as by other pathways occurs in
      a predominantly error-free manner in human cells. We discuss the implications of
      these observations for the mechanisms that could affect the efficiency and
      fidelity of TLS Pols.

PMID- 29330302
TI  - Controlled dimerization of insulin-like growth factor-1 and insulin receptors
      reveals shared and distinct activities of holo and hybrid receptors.
AB  - Breast cancer development and progression are influenced by insulin-like growth
      factor receptor 1 (IGF1R) and insulin receptor (InsR) signaling, which drive
      cancer phenotypes such as cell growth, proliferation, and migration. IGF1R and
      InsR form IGF1R/InsR hybrid receptors (HybRs) consisting of one molecule of IGF1R
      and one molecule of InsR. The specific signaling and functions of HybR are
      largely unknown, as HybR is activated by both IGF1 and insulin, and no cellular
      system expresses HybR in the absence of holo-IGF1R or holo-InsR. Here we studied
      the role of HybR by constructing inducible chimeric receptors and compared HybR
      signaling with that of holo-IGF1R and holo-InsR. We cloned chemically inducible
      chimeric IGF1R and InsR constructs consisting of the extracellular domains of the
      p75 nerve growth factor receptor fused to the intracellular beta subunit of IGF1R
      or InsR and a dimerization domain. Dimerization with the drugs AP20187 or AP21967
      allowed specific and independent activation of holo-IGF1R, holo-InsR, or HybR,
      resulting in activation of the PI3K pathway. Holo-IGF1R and HybR both promoted
      cell proliferation and glucose uptake, whereas holo-InsR only promoted glucose
      uptake, and only holo-IGF1R showed anti-apoptotic effects. We also found that the
      three receptors differentially regulated gene expression: holo-IGF1R and HybR up
      regulated EGR3; holo-InsR specifically down-regulated JUN and BCL2L1; holo-InsR
      down-regulated but HybR up-regulated HK2; and HybR specifically up-regulated
      FHL2, ITGA6, and PCK2. Our findings suggest that, when expressed and activated in
      mammary epithelial cells, HybR acts in a manner similar to IGF1R and support
      further investigation of the role of HybR in breast cancer.

PMID- 29330303
TI  - Mammalian amyloidogenic proteins promote prion nucleation in yeast.
AB  - Fibrous cross-beta aggregates (amyloids) and their transmissible forms (prions)
      cause diseases in mammals (including humans) and control heritable traits in
      yeast. Initial nucleation of a yeast prion by transiently overproduced prion
      forming protein or its (typically, QN-rich) prion domain is efficient only in the
      presence of another aggregated (in most cases, QN-rich) protein. Here, we
      demonstrate that a fusion of the prion domain of yeast protein Sup35 to some non
      QN-rich mammalian proteins, associated with amyloid diseases, promotes nucleation
      of Sup35 prions in the absence of pre-existing aggregates. In contrast, both a
      fusion of the Sup35 prion domain to a multimeric non-amyloidogenic protein and
      the expression of a mammalian amyloidogenic protein that is not fused to the
      Sup35 prion domain failed to promote prion nucleation, further indicating that
      physical linkage of a mammalian amyloidogenic protein to the prion domain of a
      yeast protein is required for the nucleation of a yeast prion. Biochemical and
      cytological approaches confirmed the nucleation of protein aggregates in the
      yeast cell. Sequence alterations antagonizing or enhancing amyloidogenicity of
      human amyloid-beta (associated with Alzheimer's disease) and mouse prion protein
      (associated with prion diseases), respectively, antagonized or enhanced
      nucleation of a yeast prion by these proteins. The yeast-based prion nucleation
      assay, developed in our work, can be employed for mutational dissection of
      amyloidogenic proteins. We anticipate that it will aid in the identification of
      chemicals that influence initial amyloid nucleation and in searching for new
      amyloidogenic proteins in a variety of proteomes.

PMID- 29330304
TI  - Efficient prion disease transmission through common environmental materials.
AB  - Prion diseases are a group of fatal neurodegenerative diseases associated with a
      protein-based infectious agent, termed prion. Compelling evidence suggests that
      natural transmission of prion diseases is mediated by environmental contamination
      with infectious prions. We hypothesized that several natural and man-made
      materials, commonly found in the environments of wild and captive animals, can
      bind prions and may act as vectors for disease transmission. To test our
      hypothesis, we exposed surfaces composed of various common environmental
      materials (i.e. wood, rocks, plastic, glass, cement, stainless steel, aluminum,
      and brass) to hamster-adapted 263K scrapie prions and studied their attachment
      and retention of infectivity in vitro and in vivo Our results indicated that
      these surfaces, with the sole exception of brass, efficiently bind, retain, and
      release prions. Prion replication was studied in vitro using the protein
      misfolding cyclic amplification technology, and infectivity of surface-bound
      prions was analyzed by intracerebrally challenging hamsters with contaminated
      implants. Our results revealed that virtually all prion-contaminated materials
      transmitted the disease at high rates. To investigate a more natural form of
      exposure to environmental contamination, we simply housed animals with large
      contaminated spheres made of the different materials under study. Strikingly,
      most of the hamsters developed classical clinical signs of prion disease and
      typical disease-associated brain changes. Our findings suggest that prion
      contamination of surfaces commonly present in the environment can be a source of
      disease transmission, thus expanding our understanding of the mechanisms for
      prion spreading in nature.

PMID- 29330305
TI  - Restricted processing of CD16a/Fc gamma receptor IIIa N-glycans from primary
      human NK cells impacts structure and function.
AB  - CD16a/Fc gamma receptor IIIa is the most abundant antibody Fc receptor expressed
      on human natural killer (NK) cells and activates a protective cytotoxic response
      following engagement with antibody clustered on the surface of a pathogen or
      diseased tissue. Therapeutic monoclonal antibodies (mAbs) with greater Fc
      mediated affinity for CD16a show superior therapeutic outcome; however, one
      significant factor that promotes antibody-CD16a interactions, the asparagine
      linked carbohydrates (N-glycans), remains undefined. Here, we purified CD16a from
      the primary NK cells of three donors and identified a large proportion of hybrid
      (22%) and oligomannose N-glycans (23%). These proportions indicated restricted N
      glycan processing and were unlike those of the recombinant CD16a forms, which
      have predominantly complex-type N-glycans (82%). Tethering recombinant CD16a to
      the membrane by including the transmembrane and intracellular domains and via
      coexpression with the Fc epsilon receptor gamma-chain in HEK293F cells was
      expected to produce N-glycoforms similar to NK cell-derived CD16a but yielded N
      glycoforms different from NK cell-derived CD16a and recombinant soluble CD16a. Of
      note, these differences in CD16a N-glycan composition affected antibody binding:
      CD16a with oligomannose N-glycans bound IgG1 Fc with 12-fold greater affinity
      than did CD16a having primarily complex-type and highly branched N-glycans. The
      changes in binding activity mirrored changes in NMR spectra of the two CD16a
      glycoforms, indicating that CD16a glycan composition also affects the
      glycoprotein's structure. These results indicated that CD16a from primary human
      NK cells is compositionally, and likely also functionally, distinct from commonly
      used recombinant forms. Furthermore, our study provides critical evidence that
      cell lineage determines CD16a N-glycan composition and antibody-binding affinity.

PMID- 29330306
TI  - An Rb family-independent E2F3 transcription factor variant impairs STAT5
      signaling and mammary gland remodeling during pregnancy in mice.
AB  - E2F transcription factors are regulated by binding to the retinoblastoma (Rb)
      tumor suppressor family of proteins. Previously, we reported an E2FLQ mutation
      that disrupts the binding with Rb proteins without affecting the transcriptional
      activity of E2F. We also showed that mouse embryonic fibroblasts with an E2F3LQ
      mutation exhibit increased E2F activity and more rapid cell proliferation. In
      this report, we analyzed E2F3LQ mice to further characterize the in vivo
      consequences of Rb family-independent E2F3 activity. We found that homozygous
      E2F3LQ mice were viable and had no obvious developmental defects or tumor growth.
      Our results also indicated that E2F3LQ cells largely retain normal control of
      cell proliferation in vivo However, female E2F3LQ mice had partial nursing
      defects. Examination of the E2F3LQ mammary glands revealed increased caveolin-1
      (CAV1) expression, reduced prolactin receptor/Stat5 signaling, and impaired
      pregnancy-induced cell proliferation and differentiation. Of note, ChIP
      experiments disclosed that E2F3 binds the CAV1 promoter. Furthermore, E2F3
      overexpression induced CAV1 expression, and CRISPR/CAS9-mediated E2F3 knockout
      reduced CAV1 levels and also increased prolactin receptor-induced Stat5 signaling
      in mammary epithelial cells. Our results suggest that the Rb family-independent
      E2F3 LQ variant inhibits pregnancy-induced mammary gland cell proliferation and
      differentiation by up-regulating CAV1 expression and inhibiting Stat5 signaling.

PMID- 29330307
TI  - Evidence suggests that germline RNF43 mutations are a rare cause of serrated
      polyposis.

PMID- 29330308
TI  - Survival outcomes of primary cutaneous T-cell lymphoma in HIV-infected patients:
      a national population-based study.
AB  - This study aimed to investigate clinical characteristics and survival outcomes of
      primary cutaneous T-cell lymphoma (CTCL) in HIV-infected and non-HIV-infected
      patients. All data were from the Surveillance, Epidemiology, and End Results
      program, 1973-2013, of the U.S. National Cancer Institute. Data of 318 HIV
      infected patients and 1272 non-HIV-infected patients with primary CTCL were
      analyzed. Endpoints were overall survival and cancer-specific mortality.
      Independent variables included demographics, pre-existing malignancy, treatments,
      and environmental factors. Among 8823 patients with CTCL, 318 (3.60 per cent)
      were HIV-infected and 8505 (96.40 per cent) were not. 318 HIV-infected patients
      and 1272 non-HIV-infected patients selected by matching diagnosis dates were
      analyzed, including 941 (59.2 per cent) males and 649 (40.8 per cent) females
      with mean age 58.8 years. HIV-infected patients with CTCL had higher survival and
      significantly lower risk of overall mortality than non-HIV-infected patients
      (adjusted HR 0.37, 95 per cent CI 0.24 to 0.59, P<0.001). Non-HIV-infected, age
      and black race were significant risk factors for overall mortality. Age and race
      are independent risk factors for overall mortality in primary CTCL individuals,
      and HIV-infected status is an independent protective factor, suggesting that
      advanced antiretroviral therapy restores immunity and prolongs survival in HIV
      infected patients with CTCL.

PMID- 29330309
TI  - Poverty, a risk factor overlooked: a cross-sectional cohort study comparing
      poverty rate and cardiovascular disease outcomes in the state of Florida.
AB  - The purpose of this study is to examine the relationship between poverty rate and
      heart disease in our state. A cross-sectional data analysis was performed using
      figures provided by the Center for Disease Control's Interactive Atlas of Heart
      Disease and Stroke Tables. Spearman's correlations and simple regressions were
      used to determine if there was a relationship between poverty and cardiovascular
      hospitalization rate and cardiovascular death rate. There was a positive
      monotonic correlation between poverty rate and cardiovascular hospitalization
      rate (Rho=0.384, P=0.001). There was a positive monotonic correlation between
      poverty rate and cardiovascular death rate (Rho=0.646, P<0.0001). County poverty
      rate had a statistically significant positive relationship with cardiovascular
      hospitalization and cardiovascular mortality in the state of Florida.

PMID- 29330310
TI  - Social determinants of community-level human papillomavirus vaccination coverage
      in aschool-based vaccination programme.
AB  - OBJECTIVE: To assess social patterns in human papillomavirus (HPV) vaccine
      coverage in a school-based, government-funded vaccination programme located
      within a single-payer universal healthcare system. DESIGN: We conducted a cross
      sectional analysis of HPV vaccine uptake data for the 2013-2014 school year for
      131 local authorities in England, and then evaluated the association between
      vaccine uptake and socioeconomic status at the aggregate level. DATA SOURCES: HPV
      vaccination coverage data from Public Health England's vaccine uptake guidance
      and the UK's March 2011 Census. MAIN OUTCOME MEASURES: We measured three-dose
      local authority-level vaccine series initiation to completion. RESULTS: We found
      that in local authorities where there are more high-income families, the
      vaccination rate is lower than in local authorities with more low-income
      families. Local authorities with a higher percentage of whites, compared with non
      whites, had higher HPV vaccination rates. Additionally, local authorities with
      more non-migrants had higher rates of vaccination. Local authorities with more
      education deprivation had higher rates of vaccination. Local authorities' higher
      proportions of high-status occupations had worse vaccination coverage. In
      bivariate analyses across all the socioeconomic indicators, a 1 SD change in the
      indicators was associated with about a 2.25 percentage point decrease (for
      income, education and occupation) or increase (for race and migrant composition)
      in HPV dose coverage in the local authority. In multivariable analyses, only race
      remained as a significant predictor of HPV coverage at the local authority level.
      CONCLUSIONS: Across all three doses, there are notable variations by
      socioeconomic status, with steep reverse gradients in three socioeconomic
      indicators. More quantitative and qualitative research needs to be conducted to
      determine the effects of the 2014 transition from a three-dose regimen to two
      dose regimen on vaccination coverage, especially in groups that experience lower
      rates of vaccination.

PMID- 29330311
TI  - Necrosis in anti-SRP+ and anti-HMGCR+myopathies: Role of autoantibodies and
      complement.
AB  - OBJECTIVE: To characterize muscle fiber necrosis in immune-mediated necrotizing
      myopathies (IMNM) with anti-signal recognition particle (SRP) or anti-3-hydroxy-3
      methylglutarylcoenzyme A reductase (HMGCR) antibodies and to explore its
      underlying molecular immune mechanisms. METHODS: Muscle biopsies from patients
      with IMNM were analyzed and compared to biopsies from control patients with
      myositis. In addition to immunostaining and reverse transcription PCR on muscle
      samples, in vitro immunostaining on primary muscle cells was performed. RESULTS:
      Creatine kinase levels and muscle regeneration correlated with the proportion of
      necrotic fibers (r = 0.6, p < 0.001). CD68+iNOS+ macrophages and a Th-1 immune
      environment were chiefly involved in ongoing myophagocytosis of necrotic fibers.
      T-cell densities correlated with necrosis but no signs of cytotoxicity were
      detected. Activation of the classical pathway of the complement cascade,
      accompanied by deposition of sarcolemmal immunoglobulins, featured involvement of
      humoral immunity. Presence of SRP and HMGCR proteins on altered myofibers was
      reproduced on myotubes exposed to purified patient-derived autoantibodies.
      Finally, a correlation between sarcolemmal complement deposits and fiber necrosis
      was observed (r = 0.4 and p = 0.004). Based on these observations, we propose to
      update the pathologic criteria of IMNM. CONCLUSION: These data further
      corroborate the pathogenic role of anti-SRP and anti-HMGCR autoantibodies in
      IMNM, highlighting humoral mechanisms as key players in immunity and myofiber
      necrosis.

PMID- 29330313
TI  - C-reactive protein and efficacy of antiplatelet therapy in (intracranial)
      atherosclerosis.

PMID- 29330314
TI  - Developmental Disability at School Age and Difficulty Obtaining Follow-up Data.
AB  - BACKGROUND: The relationship of developmental disability rates with difficulty
      obtaining follow-up data is unclear. With this study, we aimed to determine if
      children who attended research follow-up assessments with more difficulty had
      more disability at school age, compared with those who attended with less
      difficulty, and to establish the relationship between follow-up and disability
      rates. METHODS: Two groups, comprising 219 consecutive survivors born at <28
      weeks' gestation or at <1000 g birth weight in the state of Victoria, Australia,
      in 2005, and 218 term-born, normal birth weight controls were assessed at 8 years
      of age for neurodevelopmental disability (any of IQ <-1 SD, cerebral palsy,
      blindness, or deafness). Children were classified as either more or less
      difficult to get to attend by research nurses involved in the study. RESULTS: The
      follow-up rate was 87% for both groups. Overall, children who attended with more
      difficulty had higher rates of neurodevelopmental disability (42%; 19 of 45) than
      those who attended with less difficulty (20%; 66 of 328) (odds ratio: 3.09, 95%
      confidence interval: 1.58 to 6.01; P = .001). As the follow-up rate rose among
      the 3 individual hospitals involved in the assessments, so did the rate of
      neurodevelopmental disability (P = .025). CONCLUSIONS: Children who attend with
      more difficulty have higher rates of neurodevelopmental disability at school age
      than those who attend with less difficulty, and disability rates rise with higher
      follow-up rates. Rates of neurodevelopmental disability will be underestimated if
      researchers are not persistent enough to obtain high follow-up rates.

PMID- 29330312
TI  - High-sensitive C-reactive protein and dual antiplatelet in intracranial arterial
      stenosis.
AB  - OBJECTIVE: To determine the relationship of high-sensitive C-reactive protein
      (hsCRP) and the efficacy and safety of dual antiplatelet therapy in patients with
      and without intracranial arterial stenosis (ICAS) in the Clopidogrel in High-Risk
      Patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial. METHODS:
      A subgroup of 807 patients with both magnetic resonance angiography images and
      hsCRP measurement was analyzed. Cox proportional hazards models were used to
      assess the interaction of hsCRP levels with the effects of dual and single
      antiplatelet therapy. RESULTS: A total of 358 (44.4%) patients had ICAS and 449
      (55.6%) did not. The proportion of patients with elevated hsCRP levels was higher
      in the ICAS group than in the non-ICAS group (40.2% vs 30.1%, p = 0.003). There
      was significant interaction between hsCRP and the 2 antiplatelet therapy groups
      in their effects on recurrent stroke after adjustment for confounding factors in
      the patients with ICAS (p = 0.012), but not in those without (p = 0.256).
      Compared with aspirin alone, clopidogrel plus aspirin significantly reduced the
      risk of recurrent stroke only in the patients with ICAS and nonelevated hsCRP
      levels (adjusted hazard ratio 0.27; 95% confidence interval 0.11 to 0.69; p =
      0.006). Similar results were observed for composite vascular events. No
      significant difference in bleeding was found. CONCLUSIONS: Presence of both ICAS
      and nonelevated hsCRP levels may predict better response to dual antiplatelet
      therapy in reducing new stroke and composite vascular events in minor stroke or
      high-risk TIA patients. Further large-scale randomized and controlled clinical
      trials are needed to confirm this finding.

PMID- 29330315
TI  - Outcome of Preterm Infants With Postnatal Cytomegalovirus Infection.
AB  - OBJECTIVES: To assess whether preterm infants with postnatal cytomegalovirus
      infection develop neurologic sequelae in early childhood. METHODS: Infants <32
      weeks' gestation were prospectively screened for cytomegalovirus (CMV) at term
      equivalent age. Neurodevelopment was compared between CMV-positive and CMV
      negative infants by using the Griffiths Mental Development Scales (GMDS) at 16
      months' corrected age (CA); the Bayley Scales of Infant and Toddler Development,
      Third Edition or the GMDS at 24 to 30 months' CA; and the Wechsler Preschool and
      Primary Scale of Intelligence, Third Edition and Movement Assessment Battery for
      Children, Second Edition at 6 years of age. At 6 years old, hearing was assessed
      in CMV-positive children. RESULTS: Neurodevelopment was assessed in 356 infants
      at 16 months' CA, of whom 49 (14%) were infected and 307 (86%) were noninfected.
      Infected infants performed significantly better on the GMDS locomotor scale.
      There were no differences at 24 to 30 months' CA on the Bayley Scales of Infant
      and Toddler Development, Third Edition or GMDS. At 6 years of age, infected
      children scored lower on the Wechsler Preschool and Primary Scale of
      Intelligence, Third Edition, but mean scores were within normal range, reaching
      significance only in verbal IQ (96 [SD 17] vs 103 [SD 15] points; P = .046).
      Multiple regression indicated no impact of CMV status but significant influence
      of maternal education and ethnicity on verbal IQ. No significant differences in
      motor development were found and none of the infected children developed
      sensorineural hearing loss. CONCLUSIONS: In this cohort study, postnatal
      cytomegalovirus infection in preterm children did not have an adverse effect on
      neurodevelopment within the first 6 years of life.

PMID- 29330316
TI  - Myosin-1C uses a novel phosphoinositide-dependent pathway for nuclear
      localization.
AB  - Accurate control of macromolecule transport between nucleus and cytoplasm
      underlines several essential biological processes, including gene expression.
      According to the canonical model, nuclear import of soluble proteins is based on
      nuclear localization signals and transport factors. We challenge this view by
      showing that nuclear localization of the actin-dependent motor protein Myosin-1C
      (Myo1C) resembles the diffusion-retention mechanism utilized by inner nuclear
      membrane proteins. We show that Myo1C constantly shuttles in and out of the
      nucleus and that its nuclear localization does not require soluble factors, but
      is dependent on phosphoinositide binding. Nuclear import of Myo1C is preceded by
      its interaction with the endoplasmic reticulum, and phosphoinositide binding is
      specifically required for nuclear import, but not nuclear retention, of Myo1C.
      Our results therefore demonstrate, for the first time, that membrane association
      and binding to nuclear partners is sufficient to drive nuclear localization of
      also soluble proteins, opening new perspectives to evolution of cellular protein
      sorting mechanisms.

PMID- 29330317
TI  - tRNA production links nutrient conditions to the onset of sexual differentiation
      through the TORC1 pathway.
AB  - Target of rapamycin (TOR) kinase controls cell growth and metabolism in response
      to nutrient availability. In the fission yeast Schizosaccharomyces pombe, TOR
      complex 1 (TORC1) promotes vegetative growth and inhibits sexual differentiation
      in the presence of ample nutrients. Here, we report the isolation and
      characterization of mutants with similar phenotypes as TORC1 mutants, in that
      they initiate sexual differentiation even in nutrient-rich conditions. In most
      mutants identified, TORC1 activity is downregulated and the mutated genes are
      involved in tRNA expression or modification. Expression of tRNA precursors
      decreases when cells undergo sexual differentiation. Furthermore, overexpression
      of tRNA precursors prevents TORC1 downregulation upon nitrogen starvation and
      represses the initiation of sexual differentiation. Based on these observations,
      we propose that tRNA precursors operate in the S. pombe TORC1 pathway to switch
      growth mode from vegetative to reproductive.

PMID- 29330318
TI  - Shifting meiotic to mitotic spindle assembly in oocytes disrupts chromosome
      alignment.
AB  - Mitotic spindles assemble from two centrosomes, which are major microtubule
      organizing centers (MTOCs) that contain centrioles. Meiotic spindles in oocytes,
      however, lack centrioles. In mouse oocytes, spindle microtubules are nucleated
      from multiple acentriolar MTOCs that are sorted and clustered prior to completion
      of spindle assembly in an "inside-out" mechanism, ending with establishment of
      the poles. We used HSET (kinesin-14) as a tool to shift meiotic spindle assembly
      toward a mitotic "outside-in" mode and analyzed the consequences on the fidelity
      of the division. We show that HSET levels must be tightly gated in meiosis I and
      that even slight overexpression of HSET forces spindle morphogenesis to become
      more mitotic-like: rapid spindle bipolarization and pole assembly coupled with
      focused poles. The unusual length of meiosis I is not sufficient to correct these
      early spindle morphogenesis defects, resulting in severe chromosome alignment
      abnormalities. Thus, the unique "inside-out" mechanism of meiotic spindle
      assembly is essential to prevent chromosomal misalignment and production of
      aneuploidy gametes.

PMID- 29330319
TI  - Correction: A Plant-Derived Nucleic Acid Reconciles Type I IFN and a Pyroptotic
      like Event in Immunity against Respiratory Viruses.

PMID- 29330320
TI  - Cutting Edge: Homeostasis of Innate Lymphoid Cells Is Imbalanced in Psoriatic
      Arthritis.
AB  - Innate lymphoid cells (ILC) have a high potency for cytokine production
      independent of specific Ag stimulation. Imbalance of ILC subsets may influence
      cytokine production in humans and hence be associated with the development of
      inflammatory disease. Evidence for an imbalance of ILC homeostasis in human
      disease, however, is very limited to date. In this study we show that psoriatic
      arthritis (PsA), a severe disease of the joints depending on the activation of
      the IL-23/IL-17 pathway, is characterized by a skewed ILC homeostasis.
      Circulating ILC3s as potent source of IL-17/IL-22 were elevated in active PsA,
      whereas ILC2s, which produce proresolving cytokines, were decreased. The
      ILC2/ILC3 ratio was significantly correlated with clinical disease activity
      scores and the presence of imaging signs of joint inflammation and bone damage.
      Multivariable analysis showed that a high ILC2/ILC3 ratio is associated with
      remission in PsA, suggesting that specific alterations of ILC homeostasis control
      disease activity in PsA.

PMID- 29330321
TI  - Osteopontin Promotes Protective Antigenic Tolerance against Experimental Allergic
      Airway Disease.
AB  - In the context of inflammation, osteopontin (Opn) is known to promote effector
      responses, facilitating a proinflammatory environment; however, its role during
      antigenic tolerance induction is unknown. Using a mouse model of asthma, we
      investigated the role of Opn during antigenic tolerance induction and its effects
      on associated regulatory cellular populations prior to disease initiation. Our
      experiments demonstrate that Opn drives protective antigenic tolerance by
      inducing accumulation of IFN-beta-producing plasmacytoid dendritic cells, as well
      as regulatory T cells, in mediastinal lymph nodes. We also show that, in the
      absence of TLR triggers, recombinant Opn, and particularly its SLAYGLR motif,
      directly induces IFN-beta expression in Ag-primed plasmacytoid dendritic cells,
      which renders them extra protective against induction of allergic airway disease
      upon transfer into recipient mice. Lastly, we show that blockade of type I IFNR
      prevents antigenic tolerance induction against experimental allergic asthma.
      Overall, we unveil a new role for Opn in setting up a tolerogenic milieu boosting
      antigenic tolerance induction, thus leading to prevention of allergic airway
      inflammation. Our results provide insight for the future design of
      immunotherapies against allergic asthma.

PMID- 29330322
TI  - Cutting Edge: Piezo1 Mechanosensors Optimize Human T Cell Activation.
AB  - TCRs recognize peptides on MHC molecules and induce downstream signaling, leading
      to activation and clonal expansion. In addition to the strength of the
      interaction of TCRs with peptides on MHC molecules, mechanical forces contribute
      to optimal T cell activation, as reflected by the superior efficiency of
      immobilized TCR-cross-linking Abs compared with soluble Abs in TCR triggering,
      although a dedicated mechanotransduction module is not identified. We found that
      the professional mechanosensor protein Piezo1 is critically involved in human T
      cell activation. Although a deficiency in Piezo1 attenuates downstream events on
      ex vivo TCR triggering, a Piezo1 agonist can obviate the need to immobilize TCR
      cross-linking Abs. Piezo1-driven Ca2+ influx, leading to calpain activation and
      organization of cortical actin scaffold, links this mechanosensor to optimal TCR
      signaling. Thus, we discovered a hitherto unknown regulatory mechanism for human
      T cell activation and provide the first evidence, to our knowledge, for the
      involvement of Piezo1 mechanosensors in immune regulation.

PMID- 29330324
TI  - Betaine Ameliorates Experimental Autoimmune Encephalomyelitis by Inhibiting
      Dendritic Cell-Derived IL-6 Production and Th17 Differentiation.
AB  - IL-17-secreting T cells (Th17 cells) play a pathogenic role in multiple
      autoimmune diseases, including multiple sclerosis (MS), and dendritic cell (DC)
      derived cytokines play pivotal roles in promoting the differentiation of naive
      CD4+ T cells into Th cell subsets (Th1 and Th17). Therefore, small molecules
      blocking the key cytokines produced by DCs will be beneficial in MS. In this
      article, we report that betaine treatment ameliorates MS pathogenesis by
      inhibiting DC-derived IL-6 production and Th17 differentiation. Using
      experimental autoimmune encephalomyelitis, a widely used mouse model of MS, we
      found that, compared with the vehicle-treated group, betaine-treated mice
      exhibited less severe experimental autoimmune encephalomyelitis symptoms,
      including lower clinical scores, reduced leukocyte infiltration, and less
      extensive demyelination in the CNS. Moreover, a significantly lower percentage of
      Th17 cells, one of the major pathogenic effector cells in MS progression, was
      observed in the peripheral immune system and in the CNS. Interestingly, in the in
      vitro Th17-differentiation assay, no significant change in Th17 cells was
      observed between the vehicle- and betaine-treated groups, whereas in the in vitro
      DC culture experiment, betaine treatment significantly decreased DC-derived IL-6
      production. In the DC-T cell coculture experiment, a significantly decreased Th17
      differentiation was observed upon betaine treatment. All of these data
      demonstrated that betaine inhibited Th17 differentiation indirectly by reducing
      IL-6 production by DCs. In brief, our findings demonstrated the pivotal roles of
      betaine in modulating MS pathogenesis and suggested that it may serve as a
      potential novel drug candidate for the treatment of MS.

PMID- 29330323
TI  - IL-10 Deficiency Reveals a Role for TLR2-Dependent Bystander Activation of T
      Cells in Lyme Arthritis.
AB  - T cells predominate the immune responses in the synovial fluid of patients with
      persistent Lyme arthritis; however, their role in Lyme disease remains poorly
      defined. Using a murine model of persistent Lyme arthritis, we observed that
      bystander activation of CD4+ and CD8+ T cells leads to arthritis-promoting IFN
      gamma, similar to the inflammatory environment seen in the synovial tissue of
      patients with posttreatment Lyme disease. TCR transgenic mice containing
      monoclonal specificity toward non-Borrelia epitopes confirmed that bystander T
      cell activation was responsible for disease development. The microbial pattern
      recognition receptor TLR2 was upregulated on T cells following infection,
      implicating it as marker of bystander T cell activation. In fact, T cell
      intrinsic expression of TLR2 contributed to IFN-gamma production and arthritis,
      providing a mechanism for microbial-induced bystander T cell activation during
      infection. The IL-10-deficient mouse reveals a novel TLR2-intrinsic role for T
      cells in Lyme arthritis, with potentially broad application to immune
      pathogenesis.

PMID- 29330325
TI  - Cutting Edge: Plasmodium falciparum Induces Trained Innate Immunity.
AB  - Malarial infection in naive individuals induces a robust innate immune response.
      In the recently described model of innate immune memory, an initial stimulus
      primes the innate immune system to either hyperrespond (termed training) or
      hyporespond (tolerance) to subsequent immune challenge. Previous work in both
      mice and humans demonstrated that infection with malaria can both serve as a
      priming stimulus and promote tolerance to subsequent infection. In this study, we
      demonstrate that initial stimulation with Plasmodium falciparum-infected RBCs or
      the malaria crystal hemozoin induced human adherent PBMCs to hyperrespond to
      subsequent ligation of TLR2. This hyperresponsiveness correlated with increased
      H3K4me3 at important immunometabolic promoters, and these epigenetic
      modifications were also seen in Kenyan children naturally infected with malaria.
      However, the use of epigenetic and metabolic inhibitors indicated that the
      induction of trained immunity by malaria and its ligands may occur via a
      previously unrecognized mechanism(s).

PMID- 29330326
TI  - Loss of Balance between Striatal Feedforward Inhibition and Corticostriatal
      Excitation Leads to Tremor.
AB  - Fast-spiking interneurons (FSIs) exert powerful inhibitory control over the
      striatum and are hypothesized to balance the massive excitatory cortical and
      thalamic input to this structure. We recorded neuronal activity in the
      dorsolateral striatum and globus pallidus (GP) concurrently with the detailed
      movement kinematics of freely behaving female rats before and after selective
      inhibition of FSI activity using IEM-1460 microinjections. The inhibition led to
      the appearance of episodic rest tremor in the body part that depended on the
      somatotopic location of the injection within the striatum. The tremor was
      accompanied by coherent oscillations in the local field potential (LFP).
      Individual neuron activity patterns became oscillatory and coherent in the tremor
      frequency. Striatal neurons, but not GP neurons, displayed additional temporal,
      nonoscillatory correlations. The subsequent reduction in the corticostriatal
      input following muscimol injection to the corresponding somatotopic location in
      the primary motor cortex led to disruption of the tremor and a reduction of the
      LFP oscillations and individual neuron's phase-locked activity. The breakdown of
      the normal balance of excitation and inhibition in the striatum has been shown
      previously to be related to different motor abnormalities. Our results further
      indicate that the balance between excitatory corticostriatal input and
      feedforward FSI inhibition is sufficient to break down the striatal decorrelation
      process and generate oscillations resulting in rest tremor typical of multiple
      basal ganglia disorders.SIGNIFICANCE STATEMENT Fast-spiking interneurons (FSIs)
      play a key role in normal striatal processing by exerting powerful inhibitory
      control over the network. FSI malfunctions have been associated with abnormal
      processing of information within the striatum that leads to multiple movement
      disorders. Here, we study the changes in neuronal activity and movement
      kinematics following selective inhibition of these neurons. The injections led to
      the appearance of episodic rest tremor, accompanied by coherent oscillations in
      neuronal activity, which was reversed following corticostriatal inhibition. These
      results suggest that the balance between corticostriatal excitation and
      feedforward FSI inhibition is crucial for maintaining the striatal decorrelation
      process, and that its breakdown leads to the formation of oscillations resulting
      in rest tremor typical of multiple basal ganglia disorders.

PMID- 29330327
TI  - Signal Complexity of Human Intracranial EEG Tracks Successful Associative-Memory
      Formation across Individuals.
AB  - Memory performance is highly variable among individuals. Most studies examining
      human memory, however, have largely focused on the neural correlates of
      successful memory formation within individuals, rather than the differences among
      them. As such, what gives rise to this variability is poorly understood. Here, we
      examined intracranial EEG (iEEG) recordings captured from 43 participants (23
      male) implanted with subdural electrodes for seizure monitoring as they performed
      a paired-associates verbal memory task. We identified three separate but related
      signatures of neural activity that tracked differences in successful memory
      formation across individuals. High-performing individuals consistently exhibited
      less broadband power, flatter power spectral density slopes, and greater
      complexity in their iEEG signals. Furthermore, within individuals across three
      separate time scales ranging from seconds to days, successful recall was
      positively associated with these same metrics. Our data therefore suggest that
      memory ability across individuals can be indexed by increased neural signal
      complexity.SIGNIFICANCE STATEMENT We show that participants whose intracranial
      EEG exhibits less low-frequency power, flatter power spectrums, and greater
      sample entropy overall are better able to memorize associations, and that the
      same metrics track fluctuations in memory performance across time within
      individuals. These metrics together signify greater neural signal complexity,
      which may index the brain's ability to flexibly engage with information and
      generate separable memory representations. Critically, the current set of results
      provides a unique window into the neural markers of individual differences in
      memory performance, which have hitherto been underexplored.

PMID- 29330328
TI  - Assembling a Cellular User Manual for the Brain.
AB  - For many years, efforts to decipher the various cellular components that comprise
      the CNS were stymied by a lack of technical strategies for isolating and
      profiling the brain's resident cell types. The advent of transcriptional
      profiling, combined with powerful new purification schemes, changed this reality
      and transformed our understanding of the macroglial populations within the brain.
      Here, we chronicle the historical context and scientific setting for our efforts
      to transcriptionally profile neurons, astrocytes, and oligodendrocytes, and
      highlight some of the profound discoveries that were cultivated by these
      data.Following a lengthy battle with pancreatic cancer, Ben Barres passed away
      during the writing of this Progression piece. Among Ben's innumerable
      contributions to the greater scientific community, his addition of publicly
      available transcriptome databases of CNS cell types will forever remain a relic
      of his generous spirit and boundless scientific curiosity. Although he had
      impressively committed a majority of these enormous gene lists to memory, Ben
      could oftentimes be spotted at meetings buried in his cell phone on the Barres
      RNAseq database. Perhaps the only thing he enjoyed more than exploring these data
      himself, was knowing how useful these contributions had been (and will hopefully
      continue to be) to his scientific peers.

PMID- 29330329
TI  - Large genomic insertion at the Shh locus results in hammer toes through enhancer
      adoption.

PMID- 29330330
TI  - Greening up the mountain.

PMID- 29330331
TI  - Molecular pathways to nonbiting mosquitoes.

PMID- 29330332
TI  - Identification and Characterization of Sites Where Persistent Atrial Fibrillation
      Is Terminated by Localized Ablation.
AB  - BACKGROUND: The mechanisms by which persistent atrial fibrillation (AF)
      terminates via localized ablation are not well understood. To address the
      hypothesis that sites where localized ablation terminates persistent AF have
      characteristics identifiable with activation mapping during AF, we systematically
      examined activation patterns acquired only in cases of unequivocal termination by
      ablation. METHODS AND RESULTS: We recruited 57 patients with persistent AF
      undergoing ablation, in whom localized ablation terminated AF to sinus rhythm or
      organized tachycardia. For each site, we performed an offline analysis of
      unprocessed unipolar electrograms collected during AF from multipolar basket
      catheters using the maximum -dV/dt assignment to construct isochronal activation
      maps for multiple cycles. Additional computational modeling and phase analysis
      were used to study mechanisms of map variability. At all sites of AF termination,
      localized repetitive activation patterns were observed. Partial rotational
      circuits were observed in 26 of 57 (46%) cases, focal patterns in 19 of 57 (33%),
      and complete rotational activity in 12 of 57 (21%) cases. In computer
      simulations, incomplete segments of partial rotations coincided with areas of
      slow conduction characterized by complex, multicomponent electrograms, and
      variations in assigning activation times at such sites substantially altered
      mapped mechanisms. CONCLUSIONS: Local activation mapping at sites of termination
      of persistent AF showed repetitive patterns of rotational or focal activity. In
      computer simulations, complete rotational activation sequence was observed but
      was sensitive to assignment of activation timing particularly in segments of slow
      conduction. The observed phenomena of repetitive localized activation and the
      mechanism by which local ablation terminates putative AF drivers require further
      investigation.

PMID- 29330333
TI  - Standard Ablation Versus Magnetic Resonance Imaging-Guided Ablation in the
      Treatment of Ventricular Tachycardia.

PMID- 29330334
TI  - Detection of heterozygous mutation in hook microtubule-tethering protein 1 in
      three patients with decapitated and decaudated spermatozoa syndrome.
AB  - BACKGROUND: The mechanism of intramanchette transport is crucial to the
      transformation of sperm tail and the nuclear condensation during spermiogenesis.
      Although few dysfunctional proteins could result in abnormal junction between the
      head and tail of spermatozoon, little is known about the genetic cues in this
      process. OBJECTIVE: Based on patients with severe decapitated and decaudated
      spermatozoa (DDS) syndrome, the study aimed to validate whether new mutation
      exists on their Hook microtubule-tethering protein 1 (HOOK1) genes and follow
      their results of assisted reproduction treatment (ART). METHODS: 7 severe
      teratozoospermia patients with DDS (proportion >95%) and three relative members
      in one pedigree were collected to sequence the whole genomic DNA. The
      fertilisation rates (FRs) of these patients were followed. Morphological
      observation and interspecies intracytoplasmic sperm injection (ICSI) assays were
      applied. RESULTS: A novel missense mutation of A to G (p.Q286R) in patients with
      DDS (n=3/7) was found in the HOOK1 gene, which was inherited from the mother in
      one patient. This variant was absent in 160 fertile population-matched control
      individuals. Morphological observation showed that almost all the DDS broke into
      decaudated heads and headless tails at the implantation fossa or the basal plate.
      The clinical studies indicated that the mutation might cause reduced FRs on both
      ART (FR=18.07%) and interspecies ICSI (FR=16.98%). CONCLUSIONS: An unreported
      mutation in HOOK1 gene was identified, which might be responsible to some
      patients with DDS. Further studies need to uncover the molecular mechanism of
      spermiogenesis for genomic therapy.

PMID- 29330335
TI  - Fabry Disease: prevalence of affected males and heterozygotes with pathogenic GLA
      mutations identified by screening renal, cardiac and stroke clinics, 1995-2017.
AB  - BACKGROUND: Fabry Disease (FD), an X linked lysosomal storage disease due to
      pathogenic alpha-galactosidase A (GLA) mutations, results in two major subtypes,
      the early-onset Type 1 'Classic' and the Type 2 'Later-Onset' phenotypes. To
      identify previously unrecognised patients, investigators screened cardiac, renal
      and stroke clinics by enzyme assays. However, some screening studies did not
      perform confirmatory GLA mutation analyses, and many included recently recognised
      'benign/likely-benign' variants, thereby inflating prevalence estimates. METHODS:
      Online databases were searched for all FD screening studies in high-risk clinics
      (1995-2017). Studies reporting GLA mutations were re-analysed for pathogenic
      mutations, sex and phenotype. Phenotype-specific and sex-specific prevalence
      rates were determined. RESULTS: Of 67 studies, 63 that screened 51363patients
      (33943M and 17420F) and provided GLA mutations were reanalysed for disease
      causing mutations. Of reported GLA mutations, benign variants occurred in 47.9%
      of males and 74.1% of females. The following were the revised prevalence
      estimates: among 36820 (23954M and 12866F) haemodialysis screenees, 0.21% males
      and 0.15% females; among 3074 (2031M and 1043F) renal transplant screenees, 0.25%
      males and no females; among 5491 (4054M and 1437F) cardiac screenees, 0.94% males
      and 0.90% females; and among 5978 (3904M and 2074F) stroke screenees, 0.13% males
      and 0.14% females. Among male and female screenees with pathogenic mutations, the
      type 1 Classic phenotype was predominant (~60%), except more male cardiac
      patients (75%) had type 2 Later-Onset phenotype. CONCLUSIONS: Compared with
      previous findings, reanalysis of 63 studies increased the screenee numbers (~3.4
      fold), eliminated 20 benign/likely benign variants, and provided more accurate
      sex-specific and phenotype-specific prevalence estimates, ranging from ~0.13% of
      stroke to ~0.9% of cardiac male or female screenees.

PMID- 29330336
TI  - Risk factors for survival in patients with von Hippel-Lindau disease.
AB  - BACKGROUND: Historically, von Hippel-Lindau (VHL) disease is characterised by a
      poor survival. Although genotype-phenotype correlation has been described in many
      studies, the risk factors for VHL survival remain unclear. This study aims to
      evaluate the median survival of Chinese patients with VHL disease and explore
      whether VHL survival is influenced by genetic and clinical factors. METHODS: In
      this retrospective study, we recruited 340 patients from 127 VHL families. Kaplan
      Meier plot and Cox regression model were used to evaluate the median survival and
      assess how survival was influenced by birth year, birth order, sex, family
      history, mutation type, onset age and first presenting symptom. RESULTS: The
      estimated median life expectancy for Chinese patients with VHL disease was 62
      years. Patients with early-onset age, positive family history and truncating
      mutation types had poorer overall and VHL-related survival. Patients with
      haemangioblastoma as their first presenting symptom were related to a higher risk
      of death from central nervous system haemangioblastoma than those with abdominal
      lesions (HR 8.84, 95% CI 2.04 to 38.37, P=0.004). CONCLUSIONS: This largest VHL
      survival analysis indicates that onset age, family history, mutation type and
      first presenting symptom have an effect on the survival of patients with VHL
      disease, which is helpful to genetic counselling and clinical decision-making.

PMID- 29330337
TI  - Role of germline aberrations affecting CTNNA1, MAP3K6 and MYD88 in gastric cancer
      susceptibility.
AB  - BACKGROUND: In approximately 10% of all gastric cancer (GC) cases, a heritable
      cause is suspected. A subset of these cases have a causative germline CDH1
      mutation; however, in most cases the cause remains unknown. Our objective was to
      assess to what extent these remaining cases may be explained by germline
      mutations in the novel candidate GC predisposing genes CTNNA1, MAP3K6 or MYD88.
      METHODS: We sequenced a large cohort of unexplained young and/or familial
      patients with GC (n=286) without a CDH1germline mutation for germline variants
      affecting CTNNA1, MAP3K6 and MYD88 using a targeted next-generation sequencing
      approach based on single-molecule molecular inversion probes. RESULTS: Predicted
      deleterious germline variants were not encountered in MYD88, but recurrently
      observed in CTNNA1 (n=2) and MAP3K6 (n=3) in our cohort of patients with GC. In
      contrast to deleterious variants in CTNNA1, deleterious variants in MAP3K6 also
      occur frequently in the general population. CONCLUSIONS: Based on our results
      MAP3K6 should no longer be considered a GC predisposition gene, whereas
      deleterious CTNNA1 variants are confirmed as an infrequent cause of GC
      susceptibility. Biallelic MYD88 germline mutations are at most a very rare cause
      of GC susceptibility as no additional cases were identified.

PMID- 29330339
TI  - HIV-Positive Kidney Donor Selection for HIV-Positive Transplant Recipients.
AB  - The risks associated with transplanting HIV-positive kidneys into HIV-positive
      recipients have not been well studied. Since 2008, 43 kidneys from 25 HIV
      positive deceased donors have been transplanted into patients who are HIV
      positive in Cape Town, South Africa. Among the donors, 19 (76%) died secondary to
      trauma. The average age for donors was 34 (interquartile range, 19-52) years old.
      In some donors, only one kidney was used because of a limited number of suitable
      recipients on the waiting list. Only two donors had been previously exposed to
      antiretroviral triple therapy. In 23 of the deceased organ donors, the HIV status
      was not known before the time of death. Initial concerns about transplanting HIV
      positive allografts into HIV-positive recipients in this clinic revolved around
      the possibility of HIV superinfection. However, all recipients remained virally
      suppressed several years after the transplant. Only one recipient experienced an
      increased viral load after the transplant, which was related to a period of
      noncompliance on her medication. After counseling and improved compliance, the
      viral load decreased and became suppressed again. Herein, we discuss the findings
      of this study and review the literature available on this crucial topic.

PMID- 29330338
TI  - Diagnosis, management, histology and genetics of sporadic primary
      hyperparathyroidism: old knowledge with new tricks.
AB  - Primary hyperparathyroidism (pHPT) is a common endocrinopathy resulting from
      inappropriately high PTH secretion. It usually results from the presence of a
      single gland adenoma, multiple gland hyperplasia or rarely parathyroid carcinoma.
      All these conditions require different management, and it is important to be able
      to differentiate the underlined pathology, in order for the clinicians to provide
      the best therapeutic approach. Elucidation of the genetic background of each of
      these clinical entities would be of great interest. However, the molecular
      factors that control parathyroid tumorigenesis are poorly understood. There are
      data implicating the existence of specific genetic pathways involved in the
      emergence of parathyroid tumorigenesis. The main focus of the present study is to
      present the current optimal diagnostic and management protocols for pHPT as well
      as to review the literature regarding all molecular and genetic pathways that are
      to be involved in the pathophysiology of sporadic pHPT.

PMID- 29330340
TI  - The Adiponectin Receptor Agonist AdipoRon Ameliorates Diabetic Nephropathy in a
      Model of Type 2 Diabetes.
AB  - Adiponectin exerts renoprotective effects against diabetic nephropathy (DN) by
      activating the AMP-activated protein kinase (AMPK)/peroxisome proliferative
      activated receptor-alpha (PPARalpha) pathway through adiponectin receptors
      (AdipoRs). AdipoRon is an orally active synthetic adiponectin receptor agonist.
      We investigated the expression of AdipoRs and the associated intracellular
      pathways in 27 patients with type 2 diabetes and examined the effects of AdipoRon
      on DN development in male C57BLKS/J db/db mice, glomerular endothelial cells
      (GECs), and podocytes. The extent of glomerulosclerosis and tubulointerstitial
      fibrosis correlated with renal function deterioration in human kidneys.
      Expression of AdipoR1, AdipoR2, and Ca2+/calmodulin-dependent protein kinase
      kinase-beta (CaMKKbeta) and numbers of phosphorylated liver kinase B1 (LKB1)- and
      AMPK-positive cells significantly decreased in the glomeruli of early stage human
      DN. AdipoRon treatment restored diabetes-induced renal alterations in db/db mice.
      AdipoRon exerted renoprotective effects by directly activating intrarenal AdipoR1
      and AdipoR2, which increased CaMKKbeta, phosphorylated Ser431LKB1, phosphorylated
      Thr172AMPK, and PPARalpha expression independently of the systemic effects of
      adiponectin. AdipoRon-induced improvement in diabetes-induced oxidative stress
      and inhibition of apoptosis in the kidneys ameliorated relevant intracellular
      pathways associated with lipid accumulation and endothelial dysfunction. In high
      glucose-treated human GECs and murine podocytes, AdipoRon increased intracellular
      Ca2+ levels that activated a CaMKKbeta/phosphorylated Ser431LKB1/phosphorylated
      Thr172AMPK/PPARalpha pathway and downstream signaling, thus decreasing high
      glucose-induced oxidative stress and apoptosis and improving endothelial
      dysfunction. AdipoRon further produced cardioprotective effects through the same
      pathway demonstrated in the kidney. Our results show that AdipoRon ameliorates
      GEC and podocyte injury by activating the intracellular Ca2+/LKB1-AMPK/PPARalpha
      pathway, suggesting its efficacy for treating type 2 diabetes-associated DN.

PMID- 29330341
TI  - Biomechanics of coupled motion in the cervical spine during simulated whiplash in
      patients with pre-existing cervical or lumbar spinal fusion: A Finite Element
      Study.
AB  - OBJECTIVES: Loss of motion following spine segment fusion results in increased
      strain in the adjacent motion segments. However, to date, studies on the
      biomechanics of the cervical spine have not assessed the role of coupled motions
      in the lumbar spine. Accordingly, we investigated the biomechanics of the
      cervical spine following cervical fusion and lumbar fusion during simulated
      whiplash using a whole-human finite element (FE) model to simulate coupled
      motions of the spine. METHODS: A previously validated FE model of the human body
      in the driver-occupant position was used to investigate cervical hyperextension
      injury. The cervical spine was subjected to simulated whiplash exposure in
      accordance with Euro NCAP (the European New Car Assessment Programme) testing
      using the whole human FE model. The coupled motions between the cervical spine
      and lumbar spine were assessed by evaluating the biomechanical effects of
      simulated cervical fusion and lumbar fusion. RESULTS: Peak anterior longitudinal
      ligament (ALL) strain ranged from 0.106 to 0.382 in a normal spine, and from
      0.116 to 0.399 in a fused cervical spine. Strain increased from cranial to caudal
      levels. The mean strain increase in the motion segment immediately adjacent to
      the site of fusion from C2-C3 through C5-C6 was 26.1% and 50.8% following single-
      and two-level cervical fusion, respectively (p = 0.03, unpaired two-way t-test).
      Peak cervical strains following various lumbar-fusion procedures were 1.0% less
      than those seen in a healthy spine (p = 0.61, two-way ANOVA). CONCLUSION:
      Cervical arthrodesis increases peak ALL strain in the adjacent motion segments.
      C3-4 experiences greater changes in strain than C6-7. Lumbar fusion did not have
      a significant effect on cervical spine strain.Cite this article: H. Huang, R. W.
      Nightingale, A. B. C. Dang. Biomechanics of coupled motion in the cervical spine
      during simulated whiplash in patients with pre-existing cervical or lumbar spinal
      fusion: A Finite Element Study. Bone Joint Res 2018;7:28-35. DOI: 10.1302/2046
      3758.71.BJR-2017-0100.R1.

PMID- 29330342
TI  - Are the patient-rated wrist evaluation (PRWE) and the disabilities of the arm,
      shoulder and hand (DASH) questionnaire used in distal radial fractures truly
      valid and reliable?
AB  - OBJECTIVES: The patient-rated wrist evaluation (PRWE) and the Disabilities of the
      Arm, Shoulder and Hand (DASH) questionnaire are patient-reported outcome measures
      (PROMs) used for clinical and research purposes. Methodological high-quality
      clinimetric studies that determine the measurement properties of these PROMs when
      used in patients with a distal radial fracture are lacking. This study aimed to
      validate the PRWE and DASH in Dutch patients with a displaced distal radial
      fracture (DRF). METHODS: The intraclass correlation coefficient (ICC) was used
      for test-retest reliability, between PROMs completed twice with a two-week
      interval at six to eight months after DRF. Internal consistency was determined
      using Cronbach's alpha for the dimensions found in the factor analysis. The
      measurement error was expressed by the smallest detectable change (SDC). A semi
      structured interview was conducted between eight and 12 weeks after DRF to assess
      the content validity. RESULTS: A total of 119 patients (mean age 58 years (sd
      15)), 74% female, completed PROMs at a mean time of six months (sd 1) post
      fracture. One overall meaningful dimension was found for the PRWE and the DASH.
      Internal consistency was excellent for both PROMs (Cronbach's alpha 0.96 (PRWE)
      and 0.97 (DASH)). Test-retest reliability was good for the PRWE (ICC 0.87) and
      excellent for the DASH (ICC 0.91). The SDC was 20 for the PRWE and 14 for the
      DASH. No floor or ceiling effects were found. The content validity was good for
      both questionnaires. CONCLUSION: The PRWE and DASH are valid and reliable PROMs
      in assessing function and disability in Dutch patients with a displaced DRF.
      However, due to the high SDC, the PRWE and DASH are less useful for individual
      patients with a distal radial fracture in clinical practice.Cite this article: Y.
      V. Kleinlugtenbelt, R. G. Krol, M. Bhandari, J. C. Goslings, R. W. Poolman, V. A.
      B. Scholtes. Are the patient-rated wrist evaluation (PRWE) and the disabilities
      of the arm, shoulder and hand (DASH) questionnaire used in distal radial
      fractures truly valid and reliable? Bone Joint Res 2018;7:36-45. DOI:
      10.1302/2046-3758.71.BJR-2017-0081.R1.

PMID- 29330343
TI  - Treatment of osteomyelitis defects by a vancomycin-loaded gelatin/beta-tricalcium
      phosphate composite scaffold.
AB  - OBJECTIVE: In the present study, we aimed to assess whether gelatin/beta
      tricalcium phosphate (beta-TCP) composite porous scaffolds could be used as a
      local controlled release system for vancomycin. We also investigated the
      efficiency of the scaffolds in eliminating infections and repairing osteomyelitis
      defects in rabbits. METHODS: The gelatin scaffolds containing differing amounts
      of of beta-TCP (0%, 10%, 30% and 50%) were prepared for controlled release of
      vancomycin and were labelled G-TCP0, G-TCP1, G-TCP3 and G-TCP5, respectively. The
      Kirby-Bauer method was used to examine the release profile. Chronic osteomyelitis
      models of rabbits were established. After thorough debridement, the osteomyelitis
      defects were implanted with the scaffolds. Radiographs and histological
      examinations were carried out to investigate the efficiency of eliminating
      infections and repairing bone defects. RESULTS: The prepared gelatin/beta-TCP
      scaffolds exhibited a homogeneously interconnected 3D porous structure. The G
      TCP0 scaffold exhibited the longest duration of vancomycin release with a release
      duration of eight weeks. With the increase of beta-TCP contents, the release
      duration of the beta-TCP-containing composite scaffolds was decreased. The
      complete release of vancomycin from the G-TCP5 scaffold was achieved within three
      weeks. In the treatment of osteomyelitis defects in rabbits, the G-TCP3 scaffold
      showed the most efficacious performance in eliminating infections and repairing
      bone defects. CONCLUSIONS: The composite scaffolds could achieve local
      therapeutic drug levels over an extended duration. The G-TCP3 scaffold possessed
      the optimal porosity, interconnection and controlled release performance.
      Therefore, this scaffold could potentially be used in the treatment of chronic
      osteomyelitis defects.Cite this article: J. Zhou, X. G. Zhou, J. W. Wang, H.
      Zhou, J. Dong. Treatment of osteomyelitis defects by a vancomycin-loaded
      gelatin/beta-tricalcium phosphate composite scaffold. Bone Joint Res 2018;7:46
      57. DOI: 10.1302/2046-3758.71.BJR-2017-0129.R2.

PMID- 29330344
TI  - Parathyroid hormone-related protein exhibits antioxidant features in osteoblastic
      cells through its N-terminal and osteostatin domains.
AB  - OBJECTIVES: Oxidative stress plays a major role in the onset and progression of
      involutional osteoporosis. However, classical antioxidants fail to restore
      osteoblast function. Interestingly, the bone anabolism of parathyroid hormone
      (PTH) has been shown to be associated with its ability to counteract oxidative
      stress in osteoblasts. The PTH counterpart in bone, which is the PTH-related
      protein (PTHrP), displays osteogenic actions through both its N-terminal PTH-like
      region and the C-terminal domain. METHODS: We examined and compared the
      antioxidant capacity of PTHrP (1-37) with the C-terminal PTHrP domain comprising
      the 107-111 epitope (osteostatin) in both murine osteoblastic MC3T3-E1 cells and
      primary human osteoblastic cells. RESULTS: We showed that both N- and C-terminal
      PTHrP peptides at 100 nM decreased reactive oxygen species production and
      forkhead box protein O activation following hydrogen peroxide (H2O2)-induced
      oxidation, which was related to decreased lipid oxidative damage and caspase-3
      activation in these cells. This was associated with their ability to restore the
      deleterious effects of H2O2 on cell growth and alkaline phosphatase activity, as
      well as on the expression of various osteoblast differentiation genes. The
      addition of Rp-cyclic 3',5'-hydrogen phosphorothioate adenosine triethylammonium
      salt (a cyclic 3',5'-adenosine monophosphate antagonist) and calphostin C (a
      protein kinase C inhibitor), or a PTH type 1 receptor antagonist, abrogated the
      effects of N-terminal PTHrP, whereas protein phosphatase 1 (an Src kinase
      activity inhibitor), SU1498 (a vascular endothelial growth factor receptor 2
      inhibitor), or an anti osteostatin antiserum, inhibited the effects of C-terminal
      PTHrP. CONCLUSION: These findings indicate that the antioxidant properties of
      PTHrP act through its N- and C-terminal domains and provide novel insights into
      the osteogenic action of PTHrP.Cite this article: S. Portal-Nunez, J. A. Ardura,
      D. Lozano, I. Martinez de Toda, M. De la Fuente, G. Herrero-Beaumont, R. Largo,
      P. Esbrit. Parathyroid hormone-related protein exhibits antioxidant features in
      osteoblastic cells through its N-terminal and osteostatin domains. Bone Joint Res
      2018;7:58-68. DOI: 10.1302/2046-3758.71.BJR-2016-0242.R2.

PMID- 29330345
TI  - A computational simulation study to determine the biomechanical influence of
      posterior condylar offset and tibial slope in cruciate retaining total knee
      arthroplasty.
AB  - OBJECTIVES: Posterior condylar offset (PCO) and posterior tibial slope (PTS) are
      critical factors in total knee arthroplasty (TKA). A computational simulation was
      performed to evaluate the biomechanical effect of PCO and PTS on cruciate
      retaining TKA. METHODS: We generated a subject-specific computational model
      followed by the development of +/- 1 mm, +/- 2 mm and +/- 3 mm PCO models in the
      posterior direction, and -3 degrees , 0 degrees , 3 degrees  and 6 degrees  PTS
      models with each of the PCO models. Using a validated finite element (FE) model,
      we investigated the influence of the changes in PCO and PTS on the contact stress
      in the patellar button and the forces on the posterior cruciate ligament (PCL),
      patellar tendon and quadriceps muscles under the deep knee-bend loading
      conditions. RESULTS: Contact stress on the patellar button increased and
      decreased as PCO translated to the anterior and posterior directions,
      respectively. In addition, contact stress on the patellar button decreased as PTS
      increased. These trends were consistent in the FE models with altered PCO. Higher
      quadriceps muscle and patellar tendon force are required as PCO translated in the
      anterior direction with an equivalent flexion angle. However, as PTS increased,
      quadriceps muscle and patellar tendon force reduced in each PCO condition. The
      forces exerted on the PCL increased as PCO translated to the posterior direction
      and decreased as PTS increased. CONCLUSION: The change in PCO alternatively
      provided positive and negative biomechanical effects, but it led to a reduction
      in a negative biomechanical effect as PTS increased.Cite this article: K-T. Kang,
      Y-G. Koh, J. Son, O-R. Kwon, J-S. Lee, S. K. Kwon. A computational simulation
      study to determine the biomechanical influence of posterior condylar offset and
      tibial slope in cruciate retaining total knee arthroplasty. Bone Joint Res
      2018;7:69-78. DOI: 10.1302/2046-3758.71.BJR-2017-0143.R1.

PMID- 29330346
TI  - Underestimation of Staphylococcus aureus (MRSA and MSSA) carriage associated with
      standard culturing techniques: One third of carriers missed.
AB  - OBJECTIVES: Nasal carriers of Staphylococcus (S.) aureus (MRSA and MSSA) have an
      increased risk for healthcare-associated infections. There are currently limited
      national screening policies for the detection of S. aureus despite the World
      Health Organization's recommendations. This study aimed to evaluate the
      diagnostic performance of molecular and culture techniques in S. aureus
      screening, determine the cause of any discrepancy between the diagnostic
      techniques, and model the potential effect of different diagnostic techniques on
      S. aureus detection in orthopaedic patients. METHODS: Paired nasal swabs for
      polymerase chain reaction (PCR) assay and culture of S. aureus were collected
      from a study population of 273 orthopaedic outpatients due to undergo joint
      arthroplasty surgery. RESULTS: The prevalence of MSSA nasal colonization was
      found to be between 22.4% to 35.6%. The current standard direct culturing methods
      for detecting S. aureus significantly underestimated the prevalence (p = 0.005),
      failing to identify its presence in approximately one-third of patients
      undergoing joint arthroplasty surgery. CONCLUSION: Modelling these results to
      national surveillance data, it was estimated that approximately 5000 to 8000 S.
      aureus surgical site infections could be prevented, and approximately $140
      million to $950 million (approximately L110 million to L760 million) saved in
      treatment costs annually in the United States and United Kingdom combined, by
      using alternative diagnostic methods to direct culture in preoperative S. aureus
      screening and eradication programmes.Cite this article: S. T. J. Tsang, M. P.
      McHugh, D. Guerendiain, P. J. Gwynne, J. Boyd, A. H. R. W. Simpson, T. S. Walsh,
      I. F. Laurenson, K. E. Templeton. Underestimation of Staphylococcus aureus (MRSA
      and MSSA) carriage associated with standard culturing techniques: One third of
      carriers missed. Bone Joint Res 2018;7:79-84. DOI: 10.1302/2046-3758.71.BJR-2017
      0175.R1.

PMID- 29330347
TI  - Performance of candidates disclosing dyslexia with other candidates in a UK
      medical licensing examination: cross-sectional study.
AB  - PURPOSE OF THE STUDY: The aim of this study was to compare performance of
      candidates who declared an expert-confirmed diagnosis of dyslexia with all other
      candidates in the Applied Knowledge Test (AKT) of the Membership of the Royal
      College of General Practitioners licensing examination. STUDY DESIGN: We used
      routinely collected data from candidates who took the AKT on one or more
      occasions between 2010 and 2015. Multivariate logistic regression was used to
      analyse performance of candidates who declared dyslexia with all other
      candidates, adjusting for candidate characteristics known to be associated with
      examination success including age, sex, ethnicity, country of primary medical
      qualification, stage of training, number of attempts and time spent completing
      the test. RESULTS: The analysis included data from 14 examinations involving 14
      801 candidates of which 2.6% (379/14 801) declared dyslexia. The pass rate for
      candidates who declared dyslexia was 83.6% compared with 95.0% for other
      candidates. After adjusting for covariates linked to examination success
      including age, sex, ethnicity, country of primary medical qualification, stage of
      training, number of attempts and time spent completing the test dyslexia was not
      significantly associated with pass rates in the AKT. Candidates declaring
      dyslexia after initially failing the AKT were more likely to have a primary
      medical qualification outside the UK. CONCLUSIONS: Performance was similar in AKT
      candidates disclosing dyslexia with other candidates once covariates associated
      with examination success were adjusted for. Candidates declaring dyslexia after
      initially failing the AKT were more likely to have a primary medical
      qualification outside the UK.

PMID- 29330348
TI  - Weak Epistasis May Drive Adaptation in Recombining Bacteria.
AB  - The impact of epistasis on the evolution of multi-locus traits depends on
      recombination. While sexually reproducing eukaryotes recombine so frequently that
      epistasis between polymorphisms is not considered to play a large role in short
      term adaptation, many bacteria also recombine, some to the degree that their
      populations are described as "panmictic" or "freely recombining." However,
      whether this recombination is sufficient to limit the ability of selection to act
      on epistatic contributions to fitness is unknown. We quantify homologous
      recombination in five bacterial pathogens and use these parameter estimates in a
      multilocus model of bacterial evolution with additive and epistatic effects. We
      find that even for highly recombining species (e.g., Streptococcus pneumoniae or
      Helicobacter pylori), selection on weak interactions between distant mutations is
      nearly as efficient as for an asexual species, likely because homologous
      recombination typically transfers only short segments. However, for strong
      epistasis, bacterial recombination accelerates selection, with the dynamics
      dependent on the amount of recombination and the number of loci. Epistasis may
      thus play an important role in both the short- and long-term adaptive evolution
      of bacteria, and, unlike in eukaryotes, is not limited to strong effect sizes,
      closely linked loci, or other conditions that limit the impact of recombination.

PMID- 29330349
TI  - Pharmacologic inhibition of phospholipase C in the brain attenuates early memory
      formation in the honeybee (Apis mellifera L.).
AB  - Although the molecular mechanisms involved in learning and memory in insects have
      been studied intensively, the intracellular signaling mechanisms involved in
      early memory formation are not fully understood. We previously demonstrated that
      phospholipase C epsilon (PLCe), whose product is involved in calcium signaling,
      is almost selectively expressed in the mushroom bodies, a brain structure
      important for learning and memory in the honeybee. Here, we pharmacologically
      examined the role of phospholipase C (PLC) in learning and memory in the
      honeybee. First, we identified four genes for PLC subtypes in the honeybee genome
      database. Quantitative reverse transcription-polymerase chain reaction revealed
      that, among these four genes, three, including PLCe, were expressed higher in the
      brain than in sensory organs in worker honeybees, suggesting their main roles in
      the brain. Edelfosine and neomycin, pan-PLC inhibitors, significantly decreased
      PLC activities in homogenates of the brain tissues. These drugs injected into the
      head of foragers significantly attenuated memory acquisition in comparison with
      the control groups, whereas memory retention was not affected. These findings
      suggest that PLC in the brain is involved in early memory formation in the
      honeybee. To our knowledge, this is the first report of a role for PLC in
      learning and memory in an insect.

PMID- 29330350
TI  - Selection against BALB/c strain cells in mouse chimaeras.
AB  - It has been shown previously that BALB/c strain embryos tend to contribute poorly
      to mouse aggregation chimaeras. In the present study we showed that BALB/c cells
      were not preferentially allocated to any extraembryonic lineages of mouse
      aggregation chimaeras, but their contribution decreased during the early
      postimplantation period and they were significantly depleted by E8.5. The
      development of BALB/c strain preimplantation embryos lagged behind embryos from
      some other strains and the contribution that BALB/c and other embryos made to
      chimaeras correlated with their developmental stage at E2.5. This relationship
      suggests that the poor contribution of BALB/c embryos to aggregation chimaeras is
      at least partly a consequence of generalised selection related to slow or delayed
      preimplantation development. The suitability of BALB/c embryos for maximising the
      ES cell contribution to mouse ES cell chimaeras is also discussed.

PMID- 29330351
TI  - The VEGFA156b isoform is dysregulated in senescent endothelial cells and may be
      associated with prevalent and incident coronary heart disease.
AB  - Coronary heart disease (CHD) is a leading cause of morbidity in people over 65
      years of age; >40% of all deaths are due to this condition. The association
      between increasing age and CHD is well documented; the accumulation of senescent
      cells in cardiac and vascular tissues may represent one factor underpinning this
      observation. We aimed to identify senescence-related expression changes in
      primary human senescent cardiomyocytes and endothelial cells and to relate
      transcript expression in peripheral blood leucocytes to prevalent and incident
      CHD in the InCHIANTI study of aging. We quantified splicing factor expression and
      splicing patterns of candidate transcripts in proliferative and senescent later
      passage endothelial cells and cardiomyocytes using qRTPCR. Senescence-associated
      isoforms also expressed in peripheral blood leucocytes were then examined for
      associations with CHD status in 134 pairs of age, sex and BMI-matched CHD cases
      and controls. Splicing factor expression was dysregulated in senescent
      cardiomyocytes, as previously reported for endothelial cells, as was the
      expression of alternatively expressed cardiac and vascular candidate genes in
      both cell types. We found nominal associations between the expression of
      VEGFA156b and FNI-EIIIIA isoforms in peripheral blood mRNA and CHD status.
      Dysregulated splicing factor expression is a key feature of senescent
      cardiomyocytes and endothelial cells. Altered splicing of key cardiac or
      endothelial genes may contribute to the risk of CHD in the human population.

PMID- 29330352
TI  - Dbf4 recruitment by forkhead transcription factors defines an upstream rate
      limiting step in determining origin firing timing.
AB  - Initiation of eukaryotic chromosome replication follows a spatiotemporal program.
      The current model suggests that replication origins compete for a limited pool of
      initiation factors. However, it remains to be answered how these limiting factors
      are preferentially recruited to early origins. Here, we report that Dbf4 is
      enriched at early origins through its interaction with forkhead transcription
      factors Fkh1 and Fkh2. This interaction is mediated by the Dbf4 C terminus and
      was successfully reconstituted in vitro. An interaction-defective mutant,
      dbf4DeltaC, phenocopies fkh alleles in terms of origin firing. Remarkably, genome
      wide replication profiles reveal that the direct fusion of the DNA-binding domain
      (DBD) of Fkh1 to Dbf4 restores the Fkh-dependent origin firing but interferes
      specifically with the pericentromeric origin activation. Furthermore, Dbf4
      interacts directly with Sld3 and promotes the recruitment of downstream limiting
      factors. These data suggest that Fkh1 targets Dbf4 to a subset of noncentromeric
      origins to promote early replication in a manner that is reminiscent of the
      recruitment of Dbf4 to pericentromeric origins by Ctf19.

PMID- 29330353
TI  - Afadin and RhoA control pancreatic endocrine mass via lumen morphogenesis.
AB  - Proper lumen morphogenesis during pancreas development is critical to endocrine
      and exocrine cell fate. Recent studies showed that a central network of lumens
      (termed core), but not the surrounding terminal branches (termed periphery),
      produces most islet endocrine cells. To date, it remains unclear how pancreatic
      lumens form and remodel and which aspects of lumen morphogenesis influence cell
      fate. Importantly, models testing the function of the central lumen network as an
      endocrine niche are lacking. Here, we identify mechanisms underlying lumen
      formation and remodeling and show that central lumen network morphogenesis
      impacts pancreatic endocrine mass. We show that loss of the scaffolding protein
      Afadin disrupts de novo lumenogenesis and lumen continuity in the tip epithelium.
      Codepletion of the actomyosin regulator RhoA and Afadin results in defects in the
      central lumens and arrests lumen remodeling. This arrest leads to prolonged
      perdurance of the central lumen network over developmental time and expansion of
      the endocrine progenitor population and, eventually, endocrine mass. Our study
      uncovers essential roles of Afadin and RhoA in pancreatic central lumen
      morphogenesis, which subsequently determines endocrine cell mass.

PMID- 29330354
TI  - The RES complex is required for efficient transformation of the precatalytic B
      spliceosome into an activated Bact complex.
AB  - The precise function of the trimeric retention and splicing (RES) complex in pre
      mRNA splicing remains unclear. Here we dissected the role of RES during the
      assembly and activation of yeast spliceosomes. The efficiency of pre-mRNA
      splicing was significantly lower in the absence of the RES protein Snu17, and the
      recruitment of its binding partners, Pml1 (pre-mRNA leakage protein 1) and Bud13
      (bud site selection protein 13), to the spliceosome was either abolished or
      substantially reduced. RES was not required for the assembly of spliceosomal B
      complexes, but its absence hindered efficient Bact complex formation. DeltaRES
      spliceosomes were no longer strictly dependent on Prp2 activity for their
      catalytic activation, suggesting that they are structurally compromised. Addition
      of Prp2, Spp2, and UTP to affinity-purified DeltaRES B or a mixture of B/Bact
      complexes formed on wild-type pre-mRNA led to their disassembly. However, no
      substantial disassembly was observed with DeltaRES spliceosomes formed on a
      truncated pre-mRNA that allows Prp2 binding but blocks its activity. Thus, in the
      absence of RES, Prp2 appears to bind prematurely, leading to the disassembly of
      the DeltaRES B complexes to which it binds. Our data suggest that Prp2 can
      dismantle B complexes with an aberrant protein composition, suggesting that it
      may proofread the spliceosome's RNP structure prior to activation.

PMID- 29330356
TI  - Metabolic and molecular changes associated with the increased skeletal muscle
      insulin action 24-48 h after exercise in young and old humans.
AB  - The molecular and metabolic mechanisms underlying the increase in insulin
      sensitivity (i.e. increased insulin-stimulated skeletal muscle glucose uptake,
      phosphorylation and storage as glycogen) observed from 12 to 48 h following a
      single bout of exercise in humans remain unresolved. Moreover, whether these
      mechanisms differ with age is unclear. It is well established that a single bout
      of exercise increases the translocation of the glucose transporter, GLUT4, to the
      plasma membrane. Previous research using unilateral limb muscle contraction
      models in combination with hyperinsulinaemia has demonstrated that the increase
      in insulin sensitivity and glycogen synthesis 24 h after exercise is also
      associated with an increase in hexokinase II (HKII) mRNA and protein content,
      suggesting an increase in the capacity of the muscle to phosphorylate glucose and
      divert it towards glycogen synthesis. Interestingly, this response is altered in
      older individuals for up to 48 h post exercise and is associated with molecular
      changes in skeletal muscle tissue that are indicative of reduced lipid oxidation,
      increased lipogenesis, increased inflammation and a relative inflexibility of
      changes in intramyocellular lipid (IMCL) content. Reduced insulin sensitivity
      (insulin resistance) is generally related to IMCL content, particularly in the
      subsarcolemmal (SSL) region, and both are associated with increasing age. Recent
      research has demonstrated that ageing per se appears to cause an exacerbated
      lipolytic response to exercise that may result in SSL IMCL accumulation. Further
      research is required to determine if increased IMCL content affects HKII
      expression in the days after exercise in older individuals, and the effect of
      this on skeletal muscle insulin action.

PMID- 29330355
TI  - Fatty acids and related lipid mediators in the regulation of cutaneous
      inflammation.
AB  - Human skin has a distinct profile of fatty acids and related bioactive lipid
      mediators that regulate many aspects of epidermal and dermal homeostasis,
      including immune and inflammatory reactions. Sebum lipids act as effective
      antimicrobial agents, shape immune cell communications and contribute to the
      epidermal lipidome. The essential fatty acid linoleic acid is crucial for the
      structure of the epidermal barrier, while polyunsaturated fatty acids act as
      precursors to eicosanoids, octadecanoids and docosanoids through cyclooxygenase,
      lipoxygenase and cytochrome P450 monooxygenase-mediated reactions, and
      endocannabinoids and N-acyl ethanolamines. Cross-communication between these
      families of bioactive lipids suggests that their cutaneous activities should be
      considered as part of a wider metabolic network that can be targeted to maintain
      skin health, control inflammation and improve skin pathologies.

PMID- 29330357
TI  - Knockdown of Phospholipase Cepsilon (PLCepsilon) Inhibits Cell Proliferation via
      Phosphatase and Tensin Homolog Deleted on Chromosome 10 (PTEN)/AKT Signaling
      Pathway in Human Prostate Cancer.
AB  - BACKGROUND Phospholipase Cepsilon (PLCepsilon), a member of the plc family, has
      been extensively studied to reveal its role in the regulation of different cell
      functions, but understanding of the underlying mechanisms remains limited. In the
      present study, we explored the effects of PLCepsilon on PTEN (phosphatase and
      tensin homolog deleted on chromosome 10) in cell proliferation in prostate cancer
      cells. MATERIAL AND METHODS We assessed PLCepsilon and PTEN expression in human
      benign prostate tissues compared to prostate cancer tissues by
      immunohistochemistry. Lentivirus-shPLCepsilon (LV-shPLCepsilon) was designed to
      silence PLCepsilon expression in DU145 and PC3 cell lines, and the effectiveness
      was tested by qRT-PCR and Western blotting. MTT assay and colony formation assay
      were conducted to observe cell proliferation. Western blotting and
      immunofluorescence assays were used to detect changed PTEN expression in DU145.
      RESULTS We observed that PLCepsilon expression was reduced in human benign
      prostate tissues compared to prostate cancer tissues, while PTEN expression
      showed the opposite trend. Silencing of the PLCepsilon gene significantly
      inhibited cell proliferation in DU145 and PC3 cell lines. DU145 is a PTEN
      expressing cell, while PC3 is PTEN-deficient. After infection by LV-shPLCepsilon,
      we noticed that PTEN expression was up-regulated in DU145 cells but not in PC3
      cells. Furthermore, we found that PLCepsilon gene knockdown decreased P-AKT
      protein levels, but AKT protein levels were not affected. Immunofluorescence
      assays showed that PTEN expression had an intracellular distribution change in
      the DU145 cell line, and Western blot analysis showed that PTEN was obviously up
      regulated in cell nucleus and cytoplasm. CONCLUSIONS PLCepsilon is an oncogene,
      and knockdown of expression of PLCe inhibits PCa cells proliferation via the
      PTEN/AKT signaling pathway.

PMID- 29330358
TI  - Pathogenesis of bone disease in multiple myeloma: from bench to bedside.
AB  - Osteolytic bone disease is the hallmark of multiple myeloma, which deteriorates
      the quality of life of myeloma patients, and it affects dramatically their
      morbidity and mortality. The basis of the pathogenesis of myeloma-related bone
      disease is the uncoupling of the bone-remodeling process. The interaction between
      myeloma cells and the bone microenvironment ultimately leads to the activation of
      osteoclasts and suppression of osteoblasts, resulting in bone loss. Several
      intracellular and intercellular signaling cascades, including RANK/RANKL/OPG,
      Notch, Wnt, and numerous chemokines and interleukins are implicated in this
      complex process. During the last years, osteocytes have emerged as key regulators
      of bone loss in myeloma through direct interactions with the myeloma cells. The
      myeloma-induced crosstalk among the molecular pathways establishes a positive
      feedback that sustains myeloma cell survival and continuous bone destruction,
      even when a plateau phase of the disease has been achieved. Targeted therapies,
      based on the better knowledge of the biology, constitute a promising approach in
      the management of myeloma-related bone disease and several novel agents are
      currently under investigation. Herein, we provide an insight into the underlying
      pathogenesis of bone disease and discuss possible directions for future studies.

PMID- 29330359
TI  - Strong grain neighbour effects in polycrystals.
AB  - Anisotropy in single-crystal properties of polycrystals controls both the overall
      response of the aggregates and patterning of local stress/strain distributions,
      the extremes of which govern failure processes. Improving the understanding of
      grain-grain interactions has important consequences for in-service performance
      limits. Three-dimensional synchrotron X-ray diffraction was used to study the
      evolution of grain-resolved stresses over many contiguous grains in Zr and Ti
      polycrystals deformed in situ. In a significant fraction of grains, the stress
      along the loading axis was found to decrease during tensile plastic flow just
      beyond the macroscopic yield point; this is in the absence of deformation
      twinning and is a surprising behaviour. It is shown that this phenomenon is
      controlled by the crystallographic orientation of the grain and its immediate
      neighbours, particularly those adjacent along the loading axis.

PMID- 29330360
TI  - Fibre-optic metadevice for all-optical signal modulation based on coherent
      absorption.
AB  - Recently, coherent control of the optical response of thin films in standing
      waves has attracted considerable attention, ranging from applications in
      excitation-selective spectroscopy and nonlinear optics to all-optical image
      processing. Here, we show that integration of metamaterial and optical fibre
      technologies allows the use of coherently controlled absorption in a fully
      fiberized and packaged switching metadevice. With this metadevice, which controls
      light with light in a nanoscale plasmonic metamaterial film on an optical fibre
      tip, we provide proof-of-principle demonstrations of logical functions XOR, NOT
      and AND that are performed within a coherent fibre network at wavelengths between
      1530 and 1565 nm. The metadevice has been tested at up to 40 gigabits per second
      and sub-milliwatt power levels. Since coherent absorption can operate at the
      single-photon level and with 100 THz bandwidth, we argue that the demonstrated
      all-optical switch concept has potential applications in coherent and quantum
      information networks.

PMID- 29330361
TI  - Discovery of microRNA-target modules of African rice (Oryza glaberrima) under
      salinity stress.
AB  - Oryza glaberrima is the second edible rice in the genus Oryza. It is grown in the
      African countries. miRNAs are regulatory molecules that are involved in every
      domains of gene expression including salinity stress response. Although several
      miRNAs have been reported from various species of Oryza, yet none of them are
      from this species. Salt treated (200 mM NaCl for 48 h) and control smallRNA
      libraries of RAM-100, a salt tolerant genotype, each with 2 replications
      generated 150 conserve and 348 novel miRNAs. We also used smallRNAseq data of
      NCBI of O. glaberrima to discover additional 246 known miRNAs. Totally, 29 known
      and 32 novel miRNAs were differentially regulated under salinity stress. Gene
      ontology and KEGG analysis indicated several targets were involved in vital
      biological pathways of salinity stress tolerance. Expression of selected miRNAs
      as indicated by Illumina data were found to be coherent with real time-PCR
      analysis. However, target gene expression was inversely correlated with their
      corresponding miRNAs. Finally based upon present results as well as existing
      knowledge of literature, we proposed the miRNA-target modules that were induced
      by salinity stress. Therefore, the present findings provide valuable information
      about miRNA-target networks in salinity adaption of O. glaberrima.

PMID- 29330362
TI  - Dynamic modelling of the mTOR signalling network reveals complex emergent
      behaviours conferred by DEPTOR.
AB  - The mechanistic Target of Rapamycin (mTOR) signalling network is an
      evolutionarily conserved network that controls key cellular processes, including
      cell growth and metabolism. Consisting of the major kinase complexes mTOR Complex
      1 and 2 (mTORC1/2), the mTOR network harbours complex interactions and feedback
      loops. The DEP domain-containing mTOR-interacting protein (DEPTOR) was recently
      identified as an endogenous inhibitor of both mTORC1 and 2 through direct
      interactions, and is in turn degraded by mTORC1/2, adding an extra layer of
      complexity to the mTOR network. Yet, the dynamic properties of the DEPTOR-mTOR
      network and the roles of DEPTOR in coordinating mTORC1/2 activation dynamics have
      not been characterised. Using computational modelling, systems analysis and
      dynamic simulations we show that DEPTOR confers remarkably rich and complex
      dynamic behaviours to mTOR signalling, including abrupt, bistable switches,
      oscillations and co-existing bistable/oscillatory responses. Transitions between
      these distinct modes of behaviour are enabled by modulating DEPTOR expression
      alone. We characterise the governing conditions for the observed dynamics by
      elucidating the network in its vast multi-dimensional parameter space, and
      develop strategies to identify core network design motifs underlying these
      dynamics. Our findings provide new systems-level insights into the complexity of
      mTOR signalling contributed by DEPTOR.

PMID- 29330363
TI  - Disulfide isomerization reactions in titin immunoglobulin domains enable a mode
      of protein elasticity.
AB  - The response of titin to mechanical forces is a major determinant of the function
      of the heart. When placed under a pulling force, the unstructured regions of
      titin uncoil while its immunoglobulin (Ig) domains unfold and extend. Using
      single-molecule atomic force microscopy, we show that disulfide isomerization
      reactions within Ig domains enable a third mechanism of titin elasticity.
      Oxidation of Ig domains leads to non-canonical disulfide bonds that stiffen titin
      while enabling force-triggered isomerization reactions to more extended states of
      the domains. Using sequence and structural analyses, we show that 21% of titin's
      I-band Ig domains contain a conserved cysteine triad that can engage in disulfide
      isomerization reactions. We propose that imbalance of the redox status of
      myocytes can have immediate consequences for the mechanical properties of the
      sarcomere via alterations of the oxidation state of titin domains.

PMID- 29330364
TI  - Polypharmacy through Phage Display: Selection of Glucagon and GLP-1 Receptor Co
      agonists from a Phage-Displayed Peptide Library.
AB  - A promising emerging area for the treatment of obesity and diabetes is
      combinatorial hormone therapy, where single-molecule peptides are rationally
      designed to integrate the complementary actions of multiple endogenous
      metabolically-related hormones. We describe here a proof-of-concept study on
      developing unimolecular polypharmacy agents through the use of selection methods
      based on phage-displayed peptide libraries (PDL). Co-agonists of the glucagon
      (GCG) and GLP-1 receptors were identified from a PDL sequentially selected on
      GCGR- and GLP1R-overexpressing cells. After two or three rounds of selection,
      7.5% of randomly picked clones were GLP1R/GCGR co-agonists, and a further 1.53%
      were agonists of a single receptor. The phages were sequenced and 35
      corresponding peptides were synthesized. 18 peptides were potent co-agonists, 8
      of whom showed EC50 <= 30 pM on each receptor, comparable to the best rationally
      designed co-agonists reported in the literature. Based on literature examples,
      two sequences were engineered to stabilize against dipeptidyl peptidase IV
      cleavage and prolong the in vivo half-life: the engineered peptides were
      comparably potent to the parent peptides on both receptors, highlighting the
      potential use of phage-derived peptides as therapeutic agents. The strategy
      described here appears of general value for the discovery of optimized
      polypharmacology paradigms across several metabolically-related hormones.

PMID- 29330365
TI  - Engineered nanointerfaces for microfluidic isolation and molecular profiling of
      tumor-specific extracellular vesicles.
AB  - Extracellular vesicles (EVs) carry RNA, DNA, proteins, and lipids. Specifically,
      tumor-derived EVs have the potential to be utilized as disease-specific
      biomarkers. However, a lack of methods to isolate tumor-specific EVs has limited
      their use in clinical settings. Here we report a sensitive analytical
      microfluidic platform (EVHB-Chip) that enables tumor-specific EV-RNA isolation
      within 3 h. Using the EVHB-Chip, we achieve 94% tumor-EV specificity, a limit of
      detection of 100 EVs per MUL, and a 10-fold increase in tumor RNA enrichment in
      comparison to other methods. Our approach allows for the subsequent release of
      captured tumor EVs, enabling downstream characterization and functional studies.
      Processing serum and plasma samples from glioblastoma multiforme (GBM) patients,
      we can detect the mutant EGFRvIII mRNA. Moreover, using next-generation RNA
      sequencing, we identify genes specific to GBM as well as transcripts that are
      hallmarks for the four genetic subtypes of the disease.

PMID- 29330366
TI  - Each protomer of a dimeric YidC functions as a single membrane insertase.
AB  - The membrane insertase YidC catalyzes the entrance of newly synthesized proteins
      into the lipid bilayer. As an integral membrane protein itself, YidC can be found
      as a monomer, a dimer or also as a member of the holotranslocase SecYEGDF-YajC
      YidC. To investigate whether the dimeric YidC is functional and whether two
      copies cooperate to insert a single substrate, we constructed a fusion protein
      where two copies of YidC are connected by a short linker peptide. The 120 kDa
      protein is stable and functional as it supports the membrane insertion of the M13
      procoat protein, the C-tailed protein SciP and the fusion protein Pf3-Lep.
      Mutations that inhibit either protomer do not inactivate the insertase and rather
      keep it functional. When both protomers are defective, the substrate proteins
      accumulate in the cytoplasm. This suggests that the dimeric YidC operates as two
      insertases. Consistent with this, we show that the dimeric YidC can bind two
      substrate proteins simultaneously, suggesting that YidC indeed functions as a
      monomer.

PMID- 29330367
TI  - Characterization of human small heat shock protein HSPB1 alpha-crystallin domain
      localized mutants associated with hereditary motor neuron diseases.
AB  - Congenital mutations in human small heat shock protein HSPB1 (HSP27) have been
      linked to Charcot-Marie-Tooth disease, a commonly occurring peripheral
      neuropathy. Understanding the molecular mechanism of such mutations is
      indispensable towards developing future therapies for this currently incurable
      disorder. Here we describe the physico-chemical properties of the autosomal
      dominant HSPB1 mutants R127W, S135F and R136W. Despite having a nominal effect on
      thermal stability, the three mutations induce dramatic changes to quaternary
      structure. At high concentrations or under crowding conditions, the mutants form
      assemblies that are approximately two times larger than those formed by the wild
      type protein. At low concentrations, the mutants have a higher propensity to
      dissociate into small oligomers, while the dissociation of R127W and R135F
      mutants is enhanced by MAPKAP kinase-2 mediated phosphorylation. Specific
      differences are observed in the ability to form hetero-oligomers with the
      homologue HSPB6 (HSP20). For wild-type HSPB1 this only occurs at or above
      physiological temperature, whereas the R127W and S135F mutants form hetero
      oligomers with HSPB6 at 4  degrees C, and the R136W mutant fails to form hetero
      oligomers. Combined, the results suggest that the disease-related mutations of
      HSPB1 modify its self-assembly and interaction with partner proteins thus
      affecting normal functioning of HSPB1 in the cell.

PMID- 29330368
TI  - Evidence of subtle genetic structure in the sympatric species Mullus barbatus and
      Mullus surmuletus (Linnaeus, 1758) in the Mediterranean Sea.
AB  - Using thirteen microsatellite loci for Mullus barbatus and Mullus surmuletus
      collected in the Mediterranean Sea, the biogeographic boundaries, genetic
      distribution among and within basins and the impact of prolonged exploitation in
      both species were investigated as a basis for understanding their population
      dynamics and for improving Mullus spp. stock management. Different level of
      diversity indices among these co-occurring species were obtained, with M.
      barbatus showing higher allele richness and higher mean observed and expected
      heterozygosity than M. surmuletus. Reduced contemporary effective population size
      (Ne) and M-ratio values found in both species likely reflects recent demographic
      changes, due to a combination of high fishing pressures, habitat fragmentation
      and naturally occurring fluctuations in population size. Different patterns of
      genetic connectivity among populations sampled within the Mediterranean were
      observed for both species. Higher genetic structure was found for M. barbatus as
      opposed to a more homogenous pattern observed in M. surmuletus samples. Adriatic
      populations, previously considered panmictic and isolated from other
      Mediterranean regions, showed geographical partitioning within the basin but also
      population connectivity with the northern Ionian and Tyrrhenian Seas. Our results
      highlight the need for temporal sampling in understanding the complex pattern of
      population connectivity in the Mediterranean, particularly for management
      purposes.

PMID- 29330369
TI  - Bio-templated fabrication of three-dimensional network activated carbons derived
      from mycelium pellets for supercapacitor applications.
AB  - In this work, a three-dimensional porous mycelium-derived activated carbon (3D
      MAC) was fabricated via a facile bio-templating method using mycelium pellets as
      both the carbon source and the bio-template. After ZnCl2 activation and high
      temperature carbonization, the specific thread-like chain structure of mycelium
      in the pellets can be maintained effectively. The hyphae and junctions of the
      cross-linking hyphae form nanowires and carbon nanoparticles that link with the
      neighboring nanoparticles to form a network structure. By adding NH4Cl, foreign
      nitrogen element doped (N-doped) 3D-MAC was obtained, which has a hierarchical
      porous structure composed of micropores and macropores. And the multiple pore
      size distribution benefits from ZnCl2 activation, the specific 3D structure and
      gas blowing. Meanwhile, the introduction of some hydrophilic groups and abundant
      N-containing functional groups in extrinsic N-doped 3D-MAC contributes to
      improving the Faradaic pseudocapacitance, respectively. A specific capacitance of
      237.2 F g-1 at 10 mV s-1 was displayed, which is more than 1.5 times that of 3D
      MAC. Even at the large scan rate of 500 mV s-1, N-doped 3D-MAC still reveals a
      nearly symmetric rectangular shape, demonstrating great potential as a high
      performance supercapacitor electrode material due to the synergistic effects of
      its 3D hierarchical porous structure and various functional groups.

PMID- 29330370
TI  - A RNA-Sequencing approach for the identification of novel long non-coding RNA
      biomarkers in colorectal cancer.
AB  - Long non-coding RNAs (lncRNAs) have been implicated in human pathology, however,
      their role in colorectal carcinogenesis have not been fully elucidated. In the
      current study, whole-transcriptome analysis was performed in 3 pairs of
      colorectal cancer (CRC) and matched normal mucosa (NM) by RNA sequencing (RNA
      seq). Followed by confirmation using the Cancer Genome Atlas (TCGA) dataset, we
      identified 27 up-regulated and 22 down-regulated lncRNAs in CRC. Up-regulation of
      four lncRNAs, hereby named colorectal cancer associated lncRNA (CRCAL)-1
      [AC021218.2], CRCAL-2 [LINC00858], CRCAL-3 [RP11-138J23.1] and CRCAL-4 [RP11
      435O5.2], was further validated by real-time RT-PCR in 139 colorectal neoplasms
      and matched NM tissues. Knockdown of CRCAL-3 and CRCAL-4 in colon cancer cells
      reduced cell viability and colony formation ability, and induced cell cycle
      arrest. TCGA dataset supported the associations of CRCAL-3 and CRCAL-4 with cell
      cycle and revealed a co-expression network comprising dysregulated lncRNAs
      associated with protein-coding genes. In conclusion, RNA-seq identified numbers
      of novel lncRNAs dysregulated in CRC. In vitro experiments and GO term enrichment
      analysis indicated the functional relevance of CRCAL-3 and CRCAL-4 in association
      with cell cycle. Our data highlight the capability of RNA-seq to discover novel
      lncRNAs involved in human carcinogenesis, which may serve as alternative
      biomarkers and/or molecular treatment targets.

PMID- 29330371
TI  - Transcriptional inaccuracy threshold attenuates differences in RNA-dependent DNA
      synthesis fidelity between retroviral reverse transcriptases.
AB  - In M13mp2 lacZalpha forward mutation assays measuring intrinsic fidelity of DNA
      dependent DNA synthesis, wild-type human immunodeficiency virus type 1 (HIV-1)
      RTs of group M/subtype B previously showed >10-fold higher error rates than
      murine leukaemia virus (MLV) and avian myeloblastosis virus (AMV) RTs. An adapted
      version of the assay was used to obtain error rates of RNA-dependent DNA
      synthesis for several RTs, including wild-type HIV-1BH10, HIV-1ESP49, AMV and MLV
      RTs, and the high-fidelity mutants of HIV-1ESP49 RT K65R and K65R/V75I. Our
      results showed that there were less than two-fold differences in fidelity between
      the studied RTs with error rates ranging within 2.5 * 10-5 and 3.5 * 10-5. These
      results were consistent with the existence of a transcriptional inaccuracy
      threshold, generated by the RNA polymerase while synthesizing the RNA template
      used in the assay. A modest but consistent reduction of the inaccuracy threshold
      was achieved by lowering the pH and Mg2+ concentration of the transcription
      reaction. Despite assay limitations, we conclude that HIV-1BH10 and HIV-1ESP49
      RTs are less accurate when copying DNA templates than RNA templates. Analysis of
      the RNA-dependent mutational spectra revealed a higher tendency to introduce
      large deletions at the initiation of reverse transcription by all HIV-1 RTs
      except the double-mutant K65R/V75I.

PMID- 29330373
TI  - The Association of Fit-Fat Index with Incident Diabetes in Japanese Men: A
      Prospective Cohort Study.
AB  - Type 2 diabetes is increasing globally and in Asia. The purpose of this study was
      to examine the association of a fit-fat index (FFI) with diabetes incidence among
      Japanese men. In total 5,014 men aged 18-64 years old, who had an annual health
      check up with no history of major chronic disease at baseline from 2002 to 2009
      were observed. CRF was estimated via cycle ergometry. Overall, 7.6% of the men
      developed diabetes. The mean follow-up period was 5.3 years. Hazard ratios, 95%
      confidence intervals and P trend for diabetes incidence were obtained using the
      Cox proportional hazards model while adjusting for confounding variables. High
      FFI demonstrated lower risk 0.54 (0.36-0.82) compared to low BMI 0.63 (0.44
      0.90), low WHtR 0.64 (0.41-1.02), and High CRF 0.72 (0.51-1.03). FFI showed a
      marginally stronger dose response relationship across quartiles (P (trend)
      =0.001) compared to BMI (P (trend) =0.002), WHtR (P (trend) =0.055), and CRF (P
      (trend) =0.005). Overall, both fitness and fatness play independent roles in
      determining diabetes incidence in Japanese men. FFI may be a more advantageous
      physical fitness measure because it can account for changes in fitness and/or
      fatness.

PMID- 29330374
TI  - Predicting Fibrosis Progression in Renal Transplant Recipients Using Laser-Based
      Infrared Spectroscopic Imaging.
AB  - Renal transplants have not seen a significant improvement in their 10-year graft
      life. Chronic damage accumulation often leads to interstitial fibrosis and
      tubular atrophy (IF/TA) and thus graft function loss over time. For this reason,
      IF/TA has been the chief suspect for a potential prognostic marker for long term
      outcomes. In this study, we have used infrared spectroscopic (IR) imaging to
      interrogate the biochemistry of regions of fibrosis from renal transplant
      biopsies to identify a biochemical signature that can predict rapid progression
      of fibrosis. IR imaging represents an approach that permits label-free
      biochemical imaging of human tissues towards identifying novel biomarkers for
      disease diagnosis or prognosis. Two cohorts were identified as progressors (n =
      5, > 50% fibrosis increase between time points) and non-progressors (n = 5, < 5%
      increase between time points). Each patient had an early time point and late time
      point biopsy. Collagen associated carbohydrate moieties (nu(C-O), 1035 cm-1 and
      nu(C-O-C),1079 cm-1) spectral ratios demonstrated good separation between the two
      cohorts (p = 0.001). This was true for late and early time point biopsies
      suggesting the regions of fibrosis are biochemically altered in cases undergoing
      progressive fibrosis. Thus, IR imaging can potentially predict rapid progression
      of fibrosis using histologically normal early time point biopsies.

PMID- 29330372
TI  - Non-estrogenic Xanthohumol Derivatives Mitigate Insulin Resistance and Cognitive
      Impairment in High-Fat Diet-induced Obese Mice.
AB  - Xanthohumol (XN), a prenylated flavonoid from hops, improves dysfunctional
      glucose and lipid metabolism in animal models of metabolic syndrome (MetS).
      However, its metabolic transformation into the estrogenic metabolite, 8
      prenylnaringenin (8-PN), poses a potential health concern for its use in humans.
      To address this concern, we evaluated two hydrogenated derivatives, alpha,beta
      dihydro-XN (DXN) and tetrahydro-XN (TXN), which showed negligible affinity for
      estrogen receptors alpha and beta, and which cannot be metabolically converted
      into 8-PN. We compared their effects to those of XN by feeding C57BL/6J mice a
      high-fat diet (HFD) containing XN, DXN, or TXN for 13 weeks. DXN and TXN were
      present at higher concentrations than XN in plasma, liver and muscle. Mice
      administered XN, DXN or TXN showed improvements of impaired glucose tolerance
      compared to the controls. DXN and TXN treatment resulted in a decrease of HOMA-IR
      and plasma leptin. C2C12 embryonic muscle cells treated with DXN or TXN exhibited
      higher rates of uncoupled mitochondrial respiration compared to XN and the
      control. Finally, XN, DXN, or TXN treatment ameliorated HFD-induced deficits in
      spatial learning and memory. Taken together, DXN and TXN could ameliorate the
      neurocognitive-metabolic impairments associated with HFD-induced obesity without
      risk of liver injury and adverse estrogenic effects.

PMID- 29330375
TI  - Intra-Specific Latitudinal Clines in Leaf Carbon, Nitrogen, and Phosphorus and
      their Underlying Abiotic Correlates in Ruellia Nudiflora.
AB  - While plant intra-specific variation in the stoichiometry of nutrients and carbon
      is well documented, clines for such traits have been less studied, despite their
      potential to reveal the mechanisms underlying such variation. Here we analyze
      latitudinal variation in the concentration of leaf nitrogen (N), phosphorus (P),
      carbon (C) and their ratios across 30 populations of the perennial herb Ruellia
      nudiflora. In addition, we further determined whether climatic and soil variables
      underlie any such latitudinal clines in leaf traits. The sampled transect spanned
      5 degrees  latitude (ca. 900 km) and exhibited a four-fold precipitation gradient
      and 2  degrees C variation in mean annual temperature. We found that leaf P
      concentration increased with precipitation towards lower latitudes, whereas N and
      C did not exhibit latitudinal clines. In addition, N:P and C:P decreased towards
      lower latitudes and latitudinal variation in the former was weakly associated
      with soil conditions (clay content and cation exchange capacity); C:N did not
      exhibit a latitudinal gradient. Overall, these results emphasize the importance
      of addressing and disentangling the simultaneous effects of abiotic factors
      associated with intra-specific clines in plant stoichiometric traits, and
      highlight the previously underappreciated influence of abiotic factors on plant
      nutrients operating under sharp abiotic gradients over smaller spatial scales.

PMID- 29330376
TI  - Layer number identification of CVD-grown multilayer graphene using Si peak
      analysis.
AB  - Since the successful exfoliation of graphene, various methodologies have been
      developed to identify the number of layers of exfoliated graphene. The optical
      contrast, Raman G-peak intensity, and 2D-peak line-shape are currently widely
      used as the first level of inspection for graphene samples. Although the
      combination analysis of G- and 2D-peaks is powerful for exfoliated graphene
      samples, its use is limited in chemical vapor deposition (CVD)-grown graphene
      because CVD-grown graphene consists of various domains with randomly rotated
      crystallographic axes between layers, which makes the G- and 2D-peaks analysis
      difficult for use in number identification. We report herein that the Raman Si
      peak intensity can be a universal measure for the number identification of
      multilayered graphene. We synthesized a few-layered graphene via the CVD method
      and performed Raman spectroscopy. Moreover, we measured the Si-peak intensities
      from various individual graphene domains and correlated them with the
      corresponding layer numbers. We then compared the normalized Si-peak intensity of
      the CVD-grown multilayer graphene with the exfoliated multilayer graphene as a
      reference and successfully identified the layer number of the CVD-grown graphene.
      We believe that this Si-peak analysis can be further applied to various 2
      dimensional (2D) materials prepared by both exfoliation and chemical growth.

PMID- 29330378
TI  - Mechanisms controlling the impact of multi-year drought on mountain hydrology.
AB  - Mountain runoff ultimately reflects the difference between precipitation (P) and
      evapotranspiration (ET), as modulated by biogeophysical mechanisms that intensify
      or alleviate drought impacts. These modulating mechanisms are seldom measured and
      not fully understood. The impact of the warm 2012-15 California drought on the
      heavily instrumented Kings River basin provides an extraordinary opportunity to
      enumerate four mechanisms that controlled the impact of drought on mountain
      hydrology. Two mechanisms intensified the impact: (i) evaporative processes have
      first access to local precipitation, which decreased the fractional allocation of
      P to runoff in 2012-15 and reduced P-ET by 30% relative to previous years, and
      (ii) 2012-15 was 1  degrees C warmer than the previous decade, which increased ET
      relative to previous years and reduced P-ET by 5%. The other two mechanisms
      alleviated the impact: (iii) spatial heterogeneity and the continuing supply of
      runoff from higher elevations increased 2012-15 P-ET by 10% relative to that
      expected for a homogenous basin, and iv) drought-associated dieback and wildfire
      thinned the forest and decreased ET, which increased 2016 P-ET by 15%. These
      mechanisms are all important and may offset each other; analyses that neglect one
      or more will over or underestimate the impact of drought and warming on mountain
      runoff.

PMID- 29330377
TI  - Phenotypic and Functional Characterization of Peripheral Sensory Neurons derived
      from Human Embryonic Stem Cells.
AB  - The dorsal root ganglia (DRG) consist of a multitude of sensory neuronal subtypes
      that function to relay sensory stimuli, including temperature, pressure, pain and
      position to the central nervous system. Our knowledge of DRG sensory neurons have
      been predominantly driven by animal studies and considerably less is known about
      the human DRG. Human embryonic stem cells (hESC) are valuable resource to help
      close this gap. Our previous studies reported an efficient system for deriving
      neural crest and DRG sensory neurons from hESC. Here we show that this
      differentiation system gives rise to heterogeneous populations of sensory
      neuronal subtypes as demonstrated by phenotypic and functional analyses.
      Furthermore, using microelectrode arrays the maturation rate of the hESC-derived
      sensory neuronal cultures was monitored over 8 weeks in culture, showing their
      spontaneous firing activities starting at about 12 days post-differentiation and
      reaching maximum firing at about 6 weeks. These studies are highly valuable for
      developing an in vitro platform to study the diversity of sensory neuronal
      subtypes found within the human DRG.

PMID- 29330380
TI  - Automatic segmentation of the solid core and enclosed vessels in subsolid
      pulmonary nodules.
AB  - Subsolid pulmonary nodules are commonly encountered in lung cancer screening and
      clinical routine. Compared to other nodule types, subsolid nodules are associated
      with a higher malignancy probability for which the size and mass of the nodule
      and solid core are important indicators. However, reliably measuring these
      characteristics on computed tomography (CT) can be hampered by the presence of
      vessels encompassed by the nodule, since vessels have similar CT attenuation as
      solid cores. This can affect treatment decisions and patient management. We
      present a method based on voxel classification to automatically identify vessels
      and solid cores in given subsolid nodules on CT. Three experts validated our
      method on 170 screen-detected subsolid nodules from the Multicentric Italian Lung
      Disease trial. The agreement between the proposed method and the observers was
      substantial for vessel detection and moderate for solid core detection, which was
      similar to the inter-observer agreement. We found a relatively high variability
      in the inter-observer agreement and low method-observer agreements for
      delineating the borders of vessels and solid cores, illustrating the difficulty
      of this task. However, 92.4% of the proposed vessel and 80.6% of the proposed
      solid core segmentations were labeled as usable in clinical practice by the
      majority of experts.

PMID- 29330379
TI  - Identification of shared genetic variants between schizophrenia and lung cancer.
AB  - Epidemiology studies suggest associations between schizophrenia and cancer.
      However, the underlying genetic mechanisms are not well understood, and difficult
      to identify from epidemiological data. We investigated if there is a shared
      genetic architecture between schizophrenia and cancer, with the aim to identify
      specific overlapping genetic loci. First, we performed genome-wide enrichment
      analysis and second, we analyzed specific loci jointly associated with
      schizophrenia and cancer by the conjunction false discovery rate. We analyzed the
      largest genome-wide association studies of schizophrenia and lung, breast,
      prostate, ovary, and colon-rectum cancer including more than 220,000 subjects,
      and included genetic association with smoking behavior. Polygenic enrichment of
      associations with lung cancer was observed in schizophrenia, and weak enrichment
      for the remaining cancer sites. After excluding the major histocompatibility
      complex region, we identified three independent loci jointly associated with
      schizophrenia and lung cancer. The strongest association included nicotinic
      acetylcholine receptors and is an established pleiotropic locus shared between
      lung cancer and smoking. The two other loci were independent of genetic
      association with smoking. Functional analysis identified downstream pleiotropic
      effects on epigenetics and gene-expression in lung and brain tissue. These
      findings suggest that genetic factors may explain partly the observed
      epidemiological association of lung cancer and schizophrenia.

PMID- 29330381
TI  - Paper-based inkjet bioprinting to detect fluorescence resonance energy transfer
      for the assessment of anti-inflammatory activity.
AB  - For the first time, a paper-based fluorescence resonance energy transfer (FRET)
      determination with cyclic AMP (cAMP)-specific phosphodiesterase 4B (PDE4B)
      inhibitory assay using an inkjet-printing technique is proposed. Non-fabricated
      parchment paper is found to constitute a unique substrate to measure fluorescent
      energy transfer, due to its insignificant self-absorption, and enables efficient
      sample interaction. Here, we report the responsive FRET signals generated on
      paper, upon sequentially printing reaction components on parchment paper using a
      conventional inkjet printer equipped with four cartridges. After printing, the
      energy emitted by Eu chelate was transferred by FRET to ULight molecule on paper,
      detected at 665 nm. In the absence of free cAMP, a maximum FRET signal was
      achieved on paper, while a decrease in FRET signals was recorded when free cAMP
      produced by PDE4B inhibitors compete with Eu-cAMP, binding with ULight-mAb. The
      IM50 value was determined as 2.46 * 10-13 mole for roliparm and 1.86 * 10-13 mole
      for roflumilast, to effectively inhibit PDE4B activity. Inkjet printing-based
      FRET signal determination utilizes components that are less than the femtomole
      range, which was four-orders less than the standard assay method. The methodology
      reported here constitutes an innovative approach towards the determination of
      FRET signals generated on paper.

PMID- 29330382
TI  - SESN2 facilitates mitophagy by helping Parkin translocation through ULK1 mediated
      Beclin1 phosphorylation.
AB  - Mitophagy, the selective degradation of mitochondria by autophagy, is crucial for
      the maintenance of healthy mitochondrial pool in cells. The critical event in
      mitophagy is the translocation of cytosolic Parkin, a ubiquitin ligase, to the
      surface of defective mitochondria. This study elucidates a novel role of
      SESN2/Sestrin2, a stress inducible protein, in mitochondrial translocation of
      PARK2/Parkin during mitophagy. The data demonstrates that SESN2 downregulation
      inhibits BECN1/Beclin1 and Parkin interaction, thereby preventing optimum
      mitochondrial accumulation of Parkin. SESN2 interacts with ULK1 (unc-51 like
      kinase 1) and assists ULK1 mediated phosphorylation of Beclin1 at serine-14
      position required for binding with Parkin prior to mitochondrial translocation.
      The trigger for SESN2 activation and regulation of Parkin translocation is the
      generation of mitochondrial superoxide. Scavenging of mitochondrial superoxide
      lower the levels of SESN2, resulting in retardation of Parkin translocation.
      Importantly, we observe that SESN2 mediated cytosolic interaction of Parkin and
      Beclin1 is PINK1 independent but mitochondrial translocation of Parkin is PINK1
      dependent. Together, these findings suggest the role of SESN2 as a positive
      regulator of Parkin mediated mitophagy.

PMID- 29330384
TI  - Detection of Apparent Cell-free M. tuberculosis DNA from Plasma.
AB  - New diagnostics are needed to improve clinicians' ability to detect tuberculosis
      (TB) disease in key populations such as children and persons living with HIV and
      to rapidly detect drug resistance. Circulating cell-free DNA (ccfDNA) in plasma
      is a diagnostic target in new obstetric and oncologic applications, but its
      utility for diagnosing TB is not known. Here we show that Mycobacterium
      tuberculosis complex DNA can be detected in plasma of persons with sputum smear
      positive TB, even in the absence of mycobacteremia. Among 40 participants with
      bacteriologically-confirmed smear-positive TB disease who had plasma tested by
      quantitative PCR (qPCR), 18/40 (45%) had a positive result on at least one
      triplicate reaction. Our results suggest that plasma DNA may be a useful target
      for improving clinicians' ability to diagnose TB. We anticipate these findings to
      be the starting point for optimized methods of TB ccfDNA testing and sequence
      based diagnostic applications such as molecular detection of drug resistance.

PMID- 29330385
TI  - Docking, thermodynamics and molecular dynamics (MD) studies of a non-canonical
      protease inhibitor, MP-4, from Mucuna pruriens.
AB  - Sequence and structural homology suggests that MP-4 protein from Mucuna pruriens
      belongs to Kunitz-type protease inhibitor family. However, biochemical assays
      showed that this protein is a poor inhibitor of trypsin. To understand the basis
      of observed poor inhibition, thermodynamics and molecular dynamics (MD)
      simulation studies on binding of MP-4 to trypsin were carried out. Molecular
      dynamics simulations revealed that temperature influences the spectrum of
      conformations adopted by the loop regions in the MP-4 structure. At an optimal
      temperature, MP-4 achieves maximal binding while above and below the optimum
      temperature, its functional activity is hampered due to unfavourable flexibility
      and relative rigidity, respectively. The low activity at normal temperature is
      due to the widening of the conformational spectrum of the Reactive Site Loop
      (RSL) that reduces the probability of formation of stabilizing contacts with
      trypsin. The unique sequence of the RSL enhances flexibility at ambient
      temperature and thus reduces its ability to inhibit trypsin. This study shows
      that temperature influences the function of a protein through modulation in the
      structure of functional domain of the protein. Modulation of function through
      appearance of new sequences that are more sensitive to temperature may be a
      general strategy for evolution of new proteins.

PMID- 29330387
TI  - Intravesical cidofovir application in BK virus cystitis after allogeneic
      hematopoetic stem cell transplantation (HSCT) is safe and highly effective.

PMID- 29330383
TI  - Development of a PET radioligand for potassium channels to image CNS
      demyelination.
AB  - Central nervous system (CNS) demyelination represents the pathological hallmark
      of multiple sclerosis (MS) and contributes to other neurological conditions.
      Quantitative and specific imaging of demyelination would thus provide critical
      clinical insight. Here, we investigated the possibility of targeting axonal
      potassium channels to image demyelination by positron emission tomography (PET).
      These channels, which normally reside beneath the myelin sheath, become exposed
      upon demyelination and are the target of the MS drug, 4-aminopyridine (4-AP). We
      demonstrate using autoradiography that 4-AP has higher binding in non-myelinated
      and demyelinated versus well-myelinated CNS regions, and describe a fluorine
      containing derivative, 3-F-4-AP, that has similar pharmacological properties and
      can be labeled with 18F for PET imaging. Additionally, we demonstrate that [18F]3
      F-4-AP can be used to detect demyelination in rodents by PET. Further evaluation
      in Rhesus macaques shows higher binding in non-myelinated versus myelinated areas
      and excellent properties for brain imaging. Together, these data indicate that
      [18F]3-F-4-AP may be a valuable PET tracer for detecting CNS demyelination
      noninvasively.

PMID- 29330388
TI  - Donor HSCs with a preexisting ASXL1-mutation led to the development of FLT3-ITD
      positive AML in the donor and FLT3-ITD negative AML in the recipient after
      unrelated transplant.

PMID- 29330389
TI  - Accuracy and usability of the eGVHD app in assessing the severity of graft-versus
      host disease at the 2017 EBMT annual congress.

PMID- 29330386
TI  - On the detection of cerebral metabolic depression in experimental traumatic brain
      injury using Chemical Exchange Saturation Transfer (CEST)-weighted MRI.
AB  - Metabolic abnormalities are commonly observed in traumatic brain injury (TBI)
      patients exhibiting long-term neurological deficits. This study investigated the
      feasibility and reproducibility of using chemical exchange saturation transfer
      (CEST) MRI to detect cerebral metabolic depression in experimental TBI. Phantom
      and in vivo CEST experiments were conducted at 9.4 Tesla to optimize the
      selective saturation for enhancing the endogenous contrast-weighting of the
      proton exchanges over the range of glucose proton chemical shifts (glucoCEST) in
      the resting rat brain. The optimized glucoCEST-weighted imaging was performed on
      a closed-head model of diffuse TBI in rats with 2-deoxy-D-[14C]-glucose (2DG)
      autoradiography validation. The results demonstrated that saturation duration of
      1-2 seconds at pulse powers 1.5-2uT resulted in an improved contrast-to-noise
      ratio between the gray and white matter comparable to 2DG autoradiographs. The
      intrasubject (n = 4) and intersubject (n = 3) coefficient of variations for
      repeated glucoCEST acquisitions (n = 4) ranged between 8-16%. Optimization for
      the TBI study revealed that glucoCEST-weighted images with 1.5MUT power and 1 s
      saturation duration revealed the greatest changes in contrast before and after
      TBI, and positively correlated with 2DG autoradiograph (r = 0.78, p < 0.01, n =
      6) observations. These results demonstrate that glucoCEST-weighted imaging may be
      useful in detecting metabolic abnormalities following TBI.

PMID- 29330390
TI  - Freezing the graft is not necessary for autotransplants for plasma cell myeloma
      and lymphomas.
AB  - We studied rates of granulocyte and platelets recovery in 359 consecutive
      subjects receiving blood cell infusions in the context of autotransplants for
      plasma cell myeloma (N = 216) and lymphomas (N = 143). Blood cells were mobilised
      with filgrastim given for 4-5 days and collected after a median of 2 (range, 1-2)
      apheresis. Apheresis products were stored at 4 degrees  C for a median of 3 days
      (range, 2-6 days). Most subjects received carmustine, etoposide, cytarabine and
      melphalan (BEAM), cyclophosphamide, carmustine and etoposide (CBV) or high-dose
      melphalan. Filgrastim was given post transplant to 319 subjects. Median numbers
      of mononuclear cells collected was 31 * 10E + 6/kg (interquartile range (IQR) 37
      * 10E + 6 cells/kg). Median numbers of CD34-positive cells collected was 3.6 *
      10E + 6/kg (IQR 3.8 * 10E + 6/Kg). Median viability after collection was 90% (IQR
      7%) after storage, 88% (IQR 12%). A total of 255 of 256 evaluable subjects
      recovered bone marrow function and there was no late bone marrow failure. Median
      interval to neutrophils >0.5 * E + 9/L was 13 days (range, 9-39 days) and to
      platelets >20 * 10E + 9/L, 16 days (range, 7-83 days). These rates and ranges
      seem comparable to those reported after autotransplants of frozen blood cells.
      There was no correlation between numbers of storage days at 4  degrees C and
      viability afte storage (r = -0.018, p = 0.14)) nor rates of recovery of
      neutrophils (r = -0.054, p = 0.52) or platelets (r = 0.116, p = 0.14). Blood
      cells collected for autotransplant can be stored at 4  degrees C for 6 d. This
      method is simple, inexpensive and widely applicable.

PMID- 29330391
TI  - Impact of antithymocyte globulin doses in reduced intensity conditioning before
      allogeneic transplantation from matched sibling donor for patients with acute
      myeloid leukemia: a report from the acute leukemia working party of European
      group of Bone Marrow Transplantation.
AB  - Antithymocyte globulin (ATG) is commonly used for graft-vs.-host disease (GVHD)
      prophylaxis in unrelated donor allogeneic transplantation (Allo-HSCT). However,
      its use is still controversial in matched sibling donor (MSD) Allo-HSCT, notably
      after reduced intensity conditioning (RIC). ATG dose may influence the outcome,
      explaining in part the discordant conclusions in MSD Allo-HSCT. We, therefore,
      analyzed the impact of ATG doses in patients with acute myeloid leukemia in first
      complete remission undergoing RIC Allo-HSCT from a MSD. We analyzed 234 patients
      from the EBMT registry and compared outcome according to given ATG dose (high
      dose: >= 6 mg/kg, n = 39 or low dose: < 6 mg/kg, n = 195). No difference was
      found in the cumulative incidence of acute (grade 2-4: high dose vs. low dose:
      21% vs. 13%, p = 0.334; adjusted hazard ratio (HR): 1.20, p = 0.712) and chronic
      GVHD (extensive: high dose vs. low dose: 19% vs. 18%, p = 0.897; adjusted HR:
      1.01, p = 0.980). In contrast, high dose of ATG significantly increased the
      incidence of relapse (52% vs. 26%, p = 0.011; adjusted HR: 1.31, p = 0.001)
      leading to impaired outcome (HR progression-free survival (PFS): 1.23, p = 0.002;
      HR overall survival (OS): 1.17, p = 0.029; HR GVHD and relapse-free survival
      (GRFS): 1.20, p = 0.005). We conclude that an ATG dose <6 mg/kg is sufficient for
      GVHD prophylaxis, while higher doses impair disease control and outcome.

PMID- 29330392
TI  - Haploidentical hematopoietic SCT using helical tomotherapy for total-body
      irradiation and targeted dose boost in patients with high-risk/refractory acute
      lymphoblastic leukemia.
AB  - A novel conditioning regimen using helical tomotherapy (HT) was developed to
      deliver 10 Gy for total body irradiation (TBI) and simultaneously augment dose to
      12 Gy for targeted dose boost to total marrow, central nervous system leukemia,
      and extramedullary disease sites in patients with high-risk or
      relapsed/refractory acute lymphoblastic leukemia (ALL) receiving haploidentical
      allogeneic hematopoietic stem cell transplantation (allo-HSCT). Fourteen patients
      were included, eight of these patients were in first complete remission (CR1),
      one was in CR2, one had a partial response and four patients had refractory
      disease at transplantation. The median delivered average dose was 11.395 Gy
      (range 10.06-12.17). The median planning target volume D95 was 8.2 Gy (range 7.52
      9.01). The median delivered dose to skeleton bone with active bone marrow sites
      was 12.685 Gy (range 11.12-13.52). The results of this trial suggest that using
      HT TBI confers satisfactory immunosuppression and excellent eradication of
      malignant cells in patients with high-risk ALL undergoing allo-HSCT, especially
      in those with refractory ALL. After a median follow-up of 14.6 months (range 4
      28), four patients experienced non-relapse mortality, ten patients are alive in
      durable CR including remission of extramedullary leukemic infiltration. One-year
      overall survival and disease-free survival rates post-transplantation were both
      70.7%.

PMID- 29330393
TI  - Haploidentical bone marrow transplantation with post transplant cyclophosphamide
      for patients with X-linked adrenoleukodystrophy: a suitable choice in an urgent
      situation.
AB  - Allogeneic hematopoietic stem cell transplantation (HSCT) is the only treatment
      that enhances survival and stabilizes neurologic symptoms in X-linked
      adrenoleukodystrophy (X-ALD) with cerebral involvement, a severe demyelinating
      disease of childhood. Patients with X-ALD who lack a well-matched HLA donor need
      a rapid alternative. Haploidentical HSCT using post transplant cyclophosphamide
      (PT/Cy) has been performed in patients with malignant and nonmalignant diseases
      showing similar outcomes compared to other alternative sources. We describe the
      outcomes of transplants performed for nine X-ALD patients using haploidentical
      donors and PT/Cy. Patients received conditioning regimen with fludarabine 150
      mg/m2, cyclophosphamide 29 mg/kg and 2 Gy total body irradiation (TBI) with or
      without antithymocyte globulin. Graft-vs.-host disease prophylaxis consisted of
      cyclophosphamide 50 mg/kg/day on days +3 and +4, tacrolimus or cyclosporine A and
      mycophenolate mofetil. One patient had a primary graft failure and was not
      eligible for a second transplant. Three patients had secondary graft failure and
      were successfully rescued with second haploidentical transplants. Trying to
      improve engraftment, conditioning regimen was changed, substituting 2 Gy TBI for
      4 Gy total lymphoid irradiation. Eight patients are alive and engrafted (17-37
      months after transplant). Haploidentical HSCT with PT/Cy is a feasible
      alternative for X-ALD patients lacking a suitable matched donor. Graft failure
      has to be addressed in further studies.

PMID- 29330394
TI  - Impact of pretransplant leukemic blast% in bone marrow and peripheral blood on
      transplantation outcomes of patients with acute myeloid leukemia undergoing
      allogeneic stem cell transplantation in non-CR.

PMID- 29330395
TI  - Predicting failure of hematopoietic stem cell mobilization before it starts: the
      predicted poor mobilizer (pPM) score.
AB  - Predicting mobilization failure before it starts may enable patient-tailored
      strategies. Although consensus criteria for predicted PM (pPM) are available,
      their predictive performance has never been measured on real data. We
      retrospectively collected and analyzed 1318 mobilization procedures performed for
      MM and lymphoma patients in the plerixafor era. In our sample, 180/1318 (13.7%)
      were PM. The score resulting from published pPM criteria had sufficient
      performance for predicting PM, as measured by AUC (0.67, 95%CI: 0.63-0.72). We
      developed a new prediction model from multivariate analysis whose score (pPM
      score) resulted in better AUC (0.80, 95%CI: 0.76-0.84, p < 0001). pPM-score
      included as risk factors: increasing age, diagnosis of NHL, positive bone marrow
      biopsy or cytopenias before mobilization, previous mobilization failure, priming
      strategy with G-CSF alone, or without upfront plerixafor. A simplified version of
      pPM-score was categorized using a cut-off to maximize positive likelihood ratio
      (15.7, 95%CI: 9.9-24.8); specificity was 98% (95%CI: 97-98.7%), sensitivity 31.7%
      (95%CI: 24.9-39%); positive predictive value in our sample was 71.3% (95%CI: 60
      80.8%). Simplified pPM-score can "rule in" patients at very high risk for PM
      before starting mobilization, allowing changes in clinical management, such as
      choice of alternative priming strategies, to avoid highly likely mobilization
      failure.

PMID- 29330396
TI  - Comparable survival using a CMV-matched or a mismatched donor for CMV+ patients
      undergoing T-replete haplo-HSCT with PT-Cy for acute leukemia: a study of behalf
      of the infectious diseases and acute leukemia working parties of the EBMT.
AB  - The role of donor CMV serostatus in the setting of non T-cell depleted haplo-HSCT
      with post-transplant cyclophosphamide (PT-Cy) has not been specifically addressed
      so far. Here we analyzed the impact of the donor CMV serological status on the
      outcome of 983 CMV seropositive (CMV+), acute leukemia patients receiving a
      first, non T-cell depleted haplo-HSCT registered in the EBMT database. The 1-year
      NRM was 21.3% (95% CI: 18.4-24.8) and 18.8% (95% CI: 13.8-25.5) in the CMV D+/R+
      and D-/R+ pairs, respectively (p = 0.40). Similarly, 1-year OS was 55.1% (95% CI:
      50.1-58.0) and 55.7% (95% CI: 48.0-62.8) in the same groups (p = 0.50). The other
      main outcomes were comparable. No difference in NRM nor OS was observed after
      stratification for the intensity of conditioning and multivariate anaysis
      confirmed the lack of significant association with NRM or OS. In conclusion, the
      choice of a CMV-seronegative donor did not impair early survival of CMV
      seropositive patients with acute leukemia after a first, non T-cell depleted
      haploidentical HSCT and PT-Cy among this series of 983 consecutive patients.
      Future research may focus on the assessment of the hierarchy of all the donor
      variables.

PMID- 29330397
TI  - Safety and efficacy of haploidentical stem cell transplantation for multiple
      myeloma.

PMID- 29330398
TI  - Management of important adverse events associated with inotuzumab ozogamicin:
      expert panel review.

PMID- 29330399
TI  - Geriatric assessment and quality of life in older patients considered for
      allogeneic hematopoietic cell transplantation: a prospective risk factor and
      serial assessment analysis.
AB  - Allogeneic hematopoietic cell transplantation (alloHCT) in older patients
      requires the weighing of risks and benefits for this potentially curative
      treatment while facing age-related limitations. Comprehensive geriatric and
      quality of life (EORTC QLQ C-30) assessements (CGA/QOL) in addition to disease
      specific data were obtained in 108 consecutive patients (>=60 years) pre-HCT, at
      day +30, +100, and +180. Median follow-up of 106 patients alive at alloHCT was
      43.5 months, median age 66 years (range 60-78). Eighty-six (81.2%) had advanced
      disease risk at HCT and 99 (91.7%) patients received reduced intensity
      conditioning (RIC). Median PFS was 13.4 months with 38.3% (95% CI: 28.6-47.4)
      alive and in remission at 2 years; median OS was 15.6 months with 43.9% (95% CI:
      34.3-53.4) alive at 2 years. Prognostic factors for PFS were: age: HR 1.084 (95%
      CI: 1.032-1.137, p = 0.0011); HCT-CI: HR 1.13 (95% CI: 1.001-1.274, p = 0.048);
      for OS: age: HR 1.08 (95% CI: 1.031-1.139, p = 0.0017), Karnofsky Index: HR 0.97
      (95% CI: 0.954-0.996, p = 0.02); EORTC QLQ C-30 fatigue: HR 1.09 (95% CI: 1.004
      1.185, p = 0.039); Up-and-Go: HR 3.26 (95% CI: 1.001-10.6, p = 0.049). Follow-up
      assessments as time-dependent covariates were highly prognostic for OS and PFS.
      CGA/QOL confer additional prognostic utility in older alloHCT recipients.

PMID- 29330400
TI  - Acute kidney injury following haplo stem cell transplantation: incidence, risk
      factors and outcome.

PMID- 29330401
TI  - Successful management of concurrent acquired hemophilia A and a lupus
      anticoagulant in a pediatric hematopoietic stem cell transplant patient.

PMID- 29330402
TI  - Chronic graft-versus-host disease features in double unit cord blood
      transplantation according to National Institutes of Health 2005 cGVHD Consensus
      criteria.

PMID- 29330403
TI  - Ruxolitinib in steroid-refractory chronic graft-versus-host disease: experience
      of a single center.

PMID- 29330404
TI  - Association analysis between SUFU polymorphism rs17114808 and acute graft versus
      host disease after hematopoietic stem cell transplantation.

PMID- 29330405
TI  - Better outcome with haploidentical over HLA-matched related donors in patients
      with Hodgkin's lymphoma undergoing allogeneic haematopoietic cell transplantation
      a study by the Francophone Society of Bone Marrow Transplantation and Cellular
      Therapy.
AB  - The question of the best donor type between haploidentical (HAPLO) and matched
      related donors (MRD) for patients with advanced HL receiving an allogeneic
      hematopoietic cell transplantation (allo-HCT) is still debated. Given the lack of
      data comparing these two types of donor in the setting of non-myeloablative (NMA)
      or reduced-intensity (RIC) allo-HCT, we performed a multicentre retrospective
      study using graft-vs.-host disease-free relapse-free survival (GRFS) as our
      primary endpoint. We analysed the data of 151 consecutive HL patients who
      underwent NMA or RIC allo-HCT from a HAPLO (N  =  61) or MRD (N  =  90) between
      January 2011 and January 2016. GRFS was defined as the probability of being alive
      without evidence of relapse, grade 3-4 acute GVHD or chronic GVHD. In
      multivariable analysis, MRD donors were independently associated with lower GRFS
      compared to HAPLO donors (HR  =  2.95, P   < 0.001). Disease status at transplant
      other than CR was also associated with lower GRFS in multivariable analysis (HR 
      =  1.74, P  =  0.01). In addition, the administration of ATG was independently
      linked to higher GRFS (HR  =  0.52, P  =  0.009). In summary, we observed
      significantly higher GRFS in HL patients receiving an allo-HCT using the HAPLO PT
      Cy platform compared to MRD.

PMID- 29330406
TI  - Adjuvant role of SeptiFast to improve the diagnosis of sepsis in a large cohort
      of hematological patients.
AB  - Febrile neutropenia and sepsis are common and life-threatening complications in
      hematological diseases. This study was performed retrospectively in 514 patients
      treated for febrile neutropenia at our institute, to investigate the clinical
      usefulness of a molecular tool, LightCycler(r) SeptiFast test (SF), to promptly
      recognize pathogens causing sepsis in hematological patients. We collected 1837
      blood samples of 514 consecutive hematological patients. The time of processing
      is short. Overall, 757 microorganisms in 663 episodes were detected by molecular
      test and standard blood cultures (BC): 73.6% Gram-positive bacteria, 23.9% Gram
      negative bacteria, and 2.5% fungal species. This large analysis demonstrated a
      significant episode-to episode agreement (71.9%) between the two methods, higher
      in negative samples (89.14%), and a specificity of 75.89%. Clinical variables
      that gave a statistically significant contribution to their concordance were
      absolute neutrophil count, ongoing antimicrobial therapy, timing of test
      execution, and organ localization of infection. The large analysis highlights the
      potential of molecular-based assays directly performed on blood samples,
      especially if implementing the detection of antibiotic resistance genes, which
      was lacking in the used study.

PMID- 29330407
TI  - Multiscale and luminescent, hollow microspheres for gas phase thermometry.
AB  - Recently developed laser-based measurement techniques are used to image the
      temperatures and velocities in gas flows. They require new phosphor materials
      with an unprecedented combination of properties. A novel synthesis procedure is
      described here; it results in hierarchically structured, hollow microspheres of
      Eu3+-doped Y2O3, with unusual particle sizes and very good characteristics
      compared to full particles. Solution-based precipitation on polymer microballoons
      produces very stable and luminescent, ceramic materials of extremely low density.
      As a result of the - compared to established template-directed syntheses -
      reduced mass of polymer that is lost upon calcination, micron-sized particles are
      obtained with mesoporous walls, low defect concentrations, and nanoscale wall
      thicknesses. They can be produced with larger diameters (~25 um) compared to
      known hollow spheres and exhibit an optimized flow behavior. Their temperature
      sensing properties and excellent fluidic follow-up behavior are shown by
      determining emission intensity ratios in a specially designed heating chamber.
      Emission spectroscopy and imaging, electron microscopy and X-ray diffraction
      results are presented for aerosolizable Y2O3 with an optimized dopant
      concentration (8%). Challenges in the field of thermofluids can be addressed by
      combined application of thermometry and particle image velocimetry with such
      hollow microparticles.

PMID- 29330408
TI  - Collagen Type 1 Accelerates Healing of Ruptured Fetal Membranes.
AB  - Preterm premature rupture of membranes (pPROM) is a major cause of preterm birth.
      Recently, extracellular matrix-directed treatment is applied for wound healing.
      Here, we used a pregnant mouse model to test the efficacy of collagen type 1 gel
      for healing of the prematurely ruptured fetal membranes. Although injection of
      PBS into the ruptured fetal membranes resulted in 40% closure, injection of
      collagen type 1 improved closure rates to 90% within 72 h. Macrophages of the M2
      wound healing phenotype were entrapped in the collagen layer. In primary human
      amnion mesenchymal cells, collagen type 1 gels activated collagen receptor
      discoidin domain receptor 2 (DDR2) to induce myosin light chain phosphorylation
      and migration of injured amnion mesenchymal cells. These findings define the
      mechanisms for matrix-directed therapeutics for pPROM.

PMID- 29330409
TI  - Induction of ferroptosis and mitochondrial dysfunction by oxidative stress in
      PC12 cells.
AB  - Neurodegenerative diseases (NDD) are typically associated with neuron loss in
      nervous system areas. Interventions with related death mechanisms may ameliorate
      NDD progression. Oxidative stress plays an important role in NDD cell death
      routines. However, tert-butylhydroperoxide (t-BHP), a widely used oxidative
      stress stimulus, induces neural cell death through a mechanism that remains
      elusive. In our study, the ferroptosis marker events occurred after co-treatment
      with 100 MUM t-BHP for 1 h, all of which were reversed in the presence of the
      ferroptosis inhibitor ferrostatin-1 (Fer-1) and the iron chelator deferoxamine,
      implying the occurrence of ferroptosis. Moreover, mitochondrial dysfunction
      accompanied by a decreased in membrane potential and ATP production, increased
      mitochondrial ROS generation. Furthermore, this mitochondrial dysfunction could
      be reversed by Fer-1. In addition, JNK1/2 and ERK1/2 were activated upstream of
      the ferroptosis and mitochondrial dysfunction. In summary, these data suggest
      that ferroptosis, coupled with mitochondrial dysfunction, was involved in t-BHP
      induced PC12 death. JNK1/2 and ERK1/2 played important roles in t-BHP-induced
      cell death. Overall, this study might provide clues to the oxidative stress-based
      strategies for cell protection in NDD.

PMID- 29330411
TI  - X-ray-induced Scintillation Governed by Energy Transfer Process in Glasses.
AB  - The efficiency of X-ray-induced scintillation in glasses roughly depends on both
      the effective atomic number Zeff and the photoluminescence quantum efficiency
      Qeff of glass, which are useful tools for searching high-performance phosphors.
      Here, we demonstrate that the energy transfer from host to activators is also an
      important factor for attaining high scintillation efficiency in Ce-doped oxide
      glasses. The scintillation intensity of glasses with coexisting fractions of Ce3+
      and Ce4+ species is found to be higher than that of a pure-Ce3+-containing glass
      with a lower Zeff value. Values of total attenuation of each sample indicate that
      there is a non-linear correlation between the scintillation intensity and the
      product of total attenuation and Qeff. The obtained results illustrate the
      difficulty in understanding the luminescence induced by ionizing radiation,
      including the energy absorption and subsequent energy transfer. Our findings may
      provide a new approach for synthesizing novel scintillators by tailoring the
      local structure.

PMID- 29330410
TI  - The Impact of COMT and Childhood Maltreatment on Suicidal Behaviour in Affective
      Disorders.
AB  - The inconsistent findings on the association between COMT (catecholamine-O-methyl
      transferase) and suicidal behaviour gave reason to choose a clear phenotype
      description of suicidal behaviour and take childhood maltreatment as
      environmental factor into account. The aim of this candidate-gene-association
      study was to eliminate heterogeneity within the sample by only recruiting
      affective disorder patients and find associations between COMT polymorphisms and
      defined suicidal phenotypes. In a sample of 258 affective disorder patients a
      detailed clinical assessment (e.g. CTQ, SCAN, HAMD, SBQ-R, VI-SURIAS, LPC) was
      performed. DNA of peripheral blood samples was genotyped using TaqMan(r) SNP
      Genotyping Assays. We observed that the haplotype GAT of rs737865, rs6269, rs4633
      is significantly associated with suicide attempt (p = 0.003 [pcorr = 0.021]), and
      that there is a tendency towards self-harming behaviour (p = 0.02 [pcorr = 0.08])
      and also NSSI (p = 0.03 [pcorr = 0.08]), though the p values did not resist
      multiple testing correction. The same effect we observed with the 4-marker slide
      window haplotype, GATA of rs737865, rs6269, rs4633, rs4680 (p = 0.009 [pcorr =
      0.045]). The findings support an association between the COMT gene and suicidal
      behaviour phenotypes with and without childhood maltreatment as environmental
      factor.

PMID- 29330412
TI  - High expression of Endogenous Retroviruses from intrauterine life to adulthood in
      two mouse models of Autism Spectrum Disorders.
AB  - Retroelements, such as Human Endogenous Retroviruses (HERVs), have been
      implicated in many complex diseases, including neurological and neuropsychiatric
      disorders. Previously, we demonstrated a distinctive expression profile of
      specific HERV families in peripheral blood mononuclear cells from Autistic
      Spectrum Disorders (ASD) patients, suggesting their involvement in ASD. Here we
      used two distinct ASD mouse models: inbred BTBR T+tf/J mice and CD-1 outbred mice
      prenatally exposed to valproic acid. Whole embryos, blood and brain samples from
      the offspring were collected at different ages and the expression of several ERV
      families (ETnI, ETnII-alpha, ETnII-beta, ETnII-gamma, MusD and IAP),
      proinflammatory cytokines (IL-1beta, IL-6 and TNF-alpha) and Toll-like receptors
      (TLR3 and TLR4) was assessed. In the two distinct mouse models analysed, the
      transcriptional activity of the ERV families was significant higher in comparison
      with corresponding controls, in whole embryos, blood and brain samples. Also the
      expression levels of the proinflammatory cytokines and TLRs were significantly
      higher than controls. Current results are in agreement with our previous findings
      in ASD children, supporting the hypothesis that ERVs may serve as biomarkers of
      atypical brain development. Moreover, the changes in ERVs and proinflammatory
      cytokines expression could be related with the autistic-like traits acquisition
      in the two mouse models.

PMID- 29330413
TI  - Nerve wrap after end-to-end and tension-free neurorrhaphy attenuates neuropathic
      pain: A prospective study based on cohorts of digit replantation.
AB  - The repair of injured peripheral nerve is still challenging for surgeons. The end
      to-end and tension-free neurorrhaphy is the current gold standard for
      reconstruction after complete nerve transection without significant defect. The
      main objective of this study neurorrhaphy in digit replantation affects the
      sensory recovery and neuropathic pain in replanted digit. Total 101 patients who
      received replantation of single completely amputated digit were included for
      analysis in this study. In group I (n = 49), the digital nerves were repaired
      with end-to-end and tension-free neurorrhaphy and then wrapped into a tendon
      derived collagen nerve conduit. In group II (n = 52), the digital nerves were
      repaired with end-to-end and tension-free neurorrhaphy only. The static two-point
      discrimination (s2PD) was performed to evaluate sensory recovery. Visual analog
      scale (VAS) scores of pain at rest and with exertion were measured respectively.
      The s2PD tests at three and six months after surgery did not show any significant
      difference between the two groups. The VAS scores at rest and with exertion of
      group I were significantly reduced compared with those of group II at three and
      six months after surgery. Thus, we concluded that nerve wrap into a collagen
      conduit after end-to-end and tension-free neurorrhaphy could attenuate
      neuropathic pain after digit replantation but have no benefit for sensory
      recovery.

PMID- 29330414
TI  - Partially oxidized polyvinyl alcohol conduitfor peripheral nerve regeneration.
AB  - Surgical reconstruction of peripheral nerves injuries with wide substance-loss is
      still a challenge. Many studies focused on the development of artificial nerve
      conduits made of synthetic or biological materials but the ideal device has not
      yet been identified. Here, we manufactured a conduit for peripheral nerve
      regeneration using a novel biodegradable hydrogel we patented that is oxidized
      polyvinyl alcohol (OxPVA). Thus, its characteristics were compared with neat
      polyvinyl alcohol (PVA) and silk-fibroin (SF) conduits, through in vitro and in
      vivo analysis. Unlike SF, OxPVA and neat PVA scaffolds did not support SH-SY5Y
      adhesion and proliferation in vitro. After implantation in rat model of sciatic
      nerve transection, the three conduits sustained the regeneration of the injured
      nerve filling a gap of 5 mm in 12 weeks. Implanted animals showed a good gait
      recovery. Morphometric data related to the central portion of the explanted
      conduit interestingly highlighted a significantly better outcome for OxPVA
      scaffolds compared to PVA conduits in terms of axon density, also with respect to
      the autograft group. This study suggests the potential of our novel biomaterial
      for the development of conduits for clinical use in case of peripheral nerve
      lesions with substance loss.

PMID- 29330415
TI  - Unusual multiscale mechanics of biomimetic nanoparticle hydrogels.
AB  - Viscoelastic properties are central for gels and other materials. Simultaneously,
      high storage and loss moduli are difficult to attain due to their contrarian
      requirements to chemical structure. Biomimetic inorganic nanoparticles offer a
      promising toolbox for multiscale engineering of gel mechanics, but a conceptual
      framework for their molecular, nanoscale, mesoscale, and microscale engineering
      as viscoelastic materials is absent. Here we show nanoparticle gels with
      simultaneously high storage and loss moduli from CdTe nanoparticles. Viscoelastic
      figure of merit reaches 1.83 MPa exceeding that of comparable gels by 100-1000
      times for glutathione-stabilized nanoparticles. The gels made from the smallest
      nanoparticles display the highest stiffness, which was attributed to the drastic
      change of GSH configurations when nanoparticles decrease in size. A computational
      model accounting for the difference in nanoparticle interactions for variable GSH
      configurations describes the unusual trends of nanoparticle gel viscoelasticity.
      These observations are generalizable to other NP gels interconnected by
      supramolecular interactions and lead to materials with high-load bearing
      abilities and energy dissipation needed for multiple technologies.

PMID- 29330416
TI  - Virtual Genome Walking across the 32 Gb Ambystoma mexicanum genome; assembling
      gene models and intronic sequence.
AB  - Large repeat rich genomes present challenges for assembly using short read
      technologies. The 32 Gb axolotl genome is estimated to contain ~19 Gb of
      repetitive DNA making an assembly from short reads alone effectively impossible.
      Indeed, this model species has been sequenced to 20* coverage but the reads could
      not be conventionally assembled. Using an alternative strategy, we have assembled
      subsets of these reads into scaffolds describing over 19,000 gene models. We call
      this method Virtual Genome Walking as it locally assembles whole genome reads
      based on a reference transcriptome, identifying exons and iteratively extending
      them into surrounding genomic sequence. These assemblies are then linked and
      refined to generate gene models including upstream and downstream genomic, and
      intronic, sequence. Our assemblies are validated by comparison with previously
      published axolotl bacterial artificial chromosome (BAC) sequences. Our analyses
      of axolotl intron length, intron-exon structure, repeat content and synteny
      provide novel insights into the genic structure of this model species. This
      resource will enable new experimental approaches in axolotl, such as ChIP-Seq and
      CRISPR and aid in future whole genome sequencing efforts. The assembled sequences
      and annotations presented here are freely available for download from
      https://tinyurl.com/y8gydc6n . The software pipeline is available from
      https://github.com/LooseLab/iterassemble .

PMID- 29330417
TI  - High STAP1 expression in DUX4-rearranged cases is not suitable as therapeutic
      target in pediatric B-cell precursor acute lymphoblastic leukemia.
AB  - Approximately 25% of the pediatric B-cell precursor acute lymphoblastic leukemia
      (BCP-ALL) cases are genetically unclassified. More thorough elucidation of the
      pathobiology of these genetically unclassified ('B-other') cases may identify
      novel treatment options. We analyzed gene expression profiles of 572 pediatric
      BCP-ALL cases, representing all major ALL subtypes. High expression of STAP1, an
      adaptor protein downstream of the B-cell receptor (BCR), was identified in BCR
      ABL1-like and non-BCR-ABL1-like B-other cases. Limma analysis revealed an
      association between high expression of STAP1 and BCR signaling genes. However,
      STAP1 expression and pre-BCR signaling were not causally related: cytoplasmic
      IgMU levels were not abnormal in cases with high levels of STAP1 and stimulation
      of pre-BCR signaling did not induce STAP1 expression. To elucidate the role of
      STAP1 in BCP-ALL survival, expression was silenced in two human BCP-ALL cell
      lines. Knockdown of STAP1 did not reduce the proliferation rate or viability of
      these cells, suggesting that STAP1 is not a likely candidate for precision
      medicines. Moreover, high expression of STAP1 was not predictive for an
      unfavorable prognosis of BCR-ABL1-like and non-BCR-ABL1-like B-other cases.
      Remarkably, DUX4-rearrangements and intragenic ERG deletions, were enriched in
      cases harboring high expression of STAP1.

PMID- 29330418
TI  - HLA-B, HLA-C and KIR improve the predictive value of IFNL3 for Hepatitis C
      spontaneous clearance.
AB  - IFNL3 is the strongest predictor of spontaneous resolution (SR) of hepatitis C
      virus (HCV), however, consideration of IFNL3 genotype alone is of limited
      clinical value for the prediction of SR or chronic HCV infection. The objective
      of this study was to analyze the impact of HLA-B, HLA-C and KIRs on SR, as well
      as their additive effects on the predictive value of the IFNL3 genotype. We
      conducted a retrospective study of HIV patients that included both SR and chronic
      HCV patients. In our study, 61.6% of patients with IFNL3 CC achieved SR, and
      81.5% with non-CC genotypes did not achieve SR. HLA-B*44, HLA-C*12, and KIR3DS1
      were identified as predictive factors for SR, with percentages of 77.4%, 85.7%
      and 86.2%, respectively, for patients who did not experience SR. The presence of
      at least one of these three markers, defined as a genetically unfavorable profile
      (GUP), combined with the IFNL3 non-CC genotype showed a value of 100% for non-SR.
      The absence of the three markers, defined as a genetically favorable profile
      (GFP), in addition to the IFNL3 CC genotype showed a percentage of 74.1% for SR.
      The combination of these markers in addition to the IFNL3 genotype improves the
      predictive value of IFNL3 for SR of acute HCV infection in HIV patients, which
      would be clinically valuable.

PMID- 29330419
TI  - Parkinson disease with constipation: clinical features and relevant factors.
AB  - Constipation is one of the most frequent non-motor symptoms of Parkinson disease
      (PD) and it may be ignored by PD patients, leading to this problem not to be
      reported in time. The relationships between constipation and demographic
      variables, motor symptoms and other non-motor symptoms of PD are still unknown.
      PD patients were evaluated by diagnostic criteria of functional constipation in
      Rome III and divided into PD with constipation (PD-C) and PD with no constipation
      (PD-NC) groups. PD patients were assessed by rating scales of motor symptoms and
      other non-motor symptoms, activity of daily living and quality of life. The
      frequency of constipation in PD patients was 61.4%, and 24.5% of PD patients had
      constipation before the onset of motor symptoms. PD-C group had older age and age
      of onset, longer disease duration, more advanced disease stage, and more severe
      motor symptoms and non-motor symptoms, including worse cognition and emotion,
      poorer sleep quality, severer autonomic symptoms, fatigue and apathy. Binary
      Logistic regression analysis showed that the age, H-Y stage, depression, anxiety
      and autonomic dysfunction increased the risk of constipation in PD patients.
      Constipation exerted serious impact on the activity of daily living and quality
      of life in PD patients.

PMID- 29330420
TI  - Left ventricular hypertrophy and cognitive function: a systematic review.
AB  - Cognitive impairment is common in patients with hypertension. Left ventricular
      hypertrophy (LVH) is recognised as a marker of hypertension-related organ damage
      and is a strong predictor of coronary artery disease, heart failure and stroke.
      There is evidence that LVH is independently associated with cognitive impairment,
      even after adjustment for the presence of hypertension. We conducted a systematic
      review that examined cognitive impairment in adults with LVH. Independent
      searches were performed in Ovid MEDLINE, Ovid psycInfo and PubMed with the terms
      left ventricular hypertrophy and cognition. Seventy-three studies were identified
      when both searches were combined. After limiting the search to studies that were:
      (1) reported in English; (2) conducted in humans; (3) in adults aged 50 years and
      older; and (4) investigated the relationship between LVH and cognitive
      performance, nine papers were included in this systematic review. The majority of
      studies found an association between LVH and cognitive performance. Inspection of
      results indicated that individuals with LVH exhibited a lower performance in
      cognitive tests, when compared to individuals without LVH. Memory and executive
      functions were the cognitive domains that showed a specific vulnerability to the
      presence of LVH. A possible mechanism for the relationship between LVH and
      cognition is the presence of cerebral white matter damage. White matter lesions
      occur frequently in patients with LVH and may contribute to cognitive
      dysfunction. Together, the results of this review suggest that memory impairment
      and executive dysfunction are the cognitive domains that showed a particular
      association with the presence of LVH.

PMID- 29330421
TI  - Premature recruitment of oocyte pool and increased mTOR activity in Fmr1 knockout
      mice and reversal of phenotype with rapamycin.
AB  - While mutations in the fragile X mental retardation-1 (FMR1) gene are associated
      with varying reproductive outcomes in females, the effects of a complete lack of
      FMR1 expression are not known. Here, we studied the ovarian and reproductive
      phenotypes in an Fmr1 knockout (KO) mouse model and the role of mammalian target
      of rapamycin (mTOR) signaling. Breeding, histologic and mTOR signaling data were
      obtained at multiple time points in KO and wild type (WT) mice fed a control or
      rapamycin (mTOR inhibitor) diet. KO mice showed an earlier decline in ovarian
      reserve than WT mice with an increased proportion of activated follicles. mTOR
      and phosphorylated S6 kinase (p-S6K) levels, a measure of downstream mTOR
      signaling, were elevated in the KO ovaries. Rapamycin blocked these effects in KO
      mice, and increased the primordial follicle pool and age of last litter in WT
      mice. Our data demonstrates an early decline in reproductive capacity in Fmr1 KO
      mice and proposes that premature recruitment of the primordial pool via altered
      mTOR signaling may be the mechanism. Reversal of phenotypes and protein levels in
      rapamycin-treated KO mice, as well as increased reproductive lifespan of
      rapamycin-fed WT mice, suggest the mTOR pathway as a potential therapeutic
      target.

PMID- 29330422
TI  - Seabirds fighting for land: phenotypic consequences of breeding area constraints
      at a small remote archipelago.
AB  - Identifying associations between phenotypes and environmental parameters is
      crucial for understanding how natural selection acts at the individual level. In
      this context, genetically isolated populations can be useful models for
      identifying the forces selecting fitness-related traits. Here, we use a
      comprehensive dataset on a genetically and ecologically isolated population of
      the strictly marine bird, the brown booby Sula leucogaster, at the tropical and
      remote Saint Peter and Saint Paul Archipelago, mid-Atlantic Ocean, in order to
      detect phenotypic adjustments from interindividual differences in diet, foraging
      behaviour, and nest quality. For this, we took biometrics of all individuals of
      the colony breeding in 2014 and 2015 and tested their associations with nest
      quality, diet parameters, and foraging behaviour. While body size was not related
      to the foraging parameters, the body size of the females (responsible for nest
      acquisition and defence) was significantly associated with the nest quality, as
      larger females occupied high-quality nests. Our findings suggest that the small
      breeding area, rather than prey availability, is a limiting factor, emphasizing
      the role of on-land features in shaping phenotypic characteristics and fitness in
      land-dependent marine vertebrates.

PMID- 29330425
TI  - Formation and dynamics of a solar eruptive flux tube.
AB  - Solar eruptions are well-known drivers of extreme space weather, which can
      greatly disturb the Earth's magnetosphere and ionosphere. The triggering process
      and initial dynamics of these eruptions are still an area of intense study. Here
      we perform a magnetohydrodynamic simulation taking into account the observed
      photospheric magnetic field to reveal the dynamics of a solar eruption in a real
      magnetic environment. In our simulation, we confirmed that tether-cutting
      reconnection occurring locally above the polarity inversion line creates a
      twisted flux tube, which is lifted into a toroidal unstable area where it loses
      equilibrium, destroying the force-free state, and driving the eruption.
      Consequently, a more highly twisted flux tube is built up during this initial
      phase, which can be further accelerated even when it returns to a stable area. We
      suggest that a nonlinear positive feedback process between the flux tube
      evolution and reconnection is the key to ensure this extra acceleration.

PMID- 29330424
TI  - Metagenomic and metabolomic analyses unveil dysbiosis of gut microbiota in
      chronic heart failure patients.
AB  - Previous studies suggested a possible gut microbiota dysbiosis in chronic heart
      failure (CHF). However, direct evidence was lacking. In this study, we
      investigated the composition and metabolic patterns of gut microbiota in CHF
      patients to provide direct evidence and comprehensive understanding of gut
      microbiota dysbiosis in CHF. We enrolled 53 CHF patients and 41 controls.
      Metagenomic analyses of faecal samples and metabolomic analyses of faecal and
      plasma samples were then performed. We found that the composition of gut
      microbiota in CHF was significantly different from controls. Faecalibacterium
      prausnitzii decrease and Ruminococcus gnavus increase were the essential
      characteristics in CHF patients' gut microbiota. We also observed an imbalance of
      gut microbes involved in the metabolism of protective metabolites such as
      butyrate and harmful metabolites such as trimethylamine N-oxide in CHF patients.
      Metabolic features of both faecal and plasma samples from CHF patients also
      significantly changed. Moreover, alterations in faecal and plasma metabolic
      patterns correlated with gut microbiota dysbiosis in CHF. Taken together, we
      found that CHF was associated with distinct gut microbiota dysbiosis and
      pinpointed the specific core bacteria imbalance in CHF, along with correlations
      between changes in certain metabolites and gut microbes.

PMID- 29330423
TI  - T cell immunity to Zika virus targets immunodominant epitopes that show cross
      reactivity with other Flaviviruses.
AB  - Zika virus (ZIKV) Infection has several outcomes from asymptomatic exposure to
      rash, conjunctivitis, Guillain-Barre syndrome or congenital Zika syndrome.
      Analysis of ZIKV immunity is confounded by the fact that several related
      Flaviviruses infect humans, including Dengue virus 1-4, West Nile virus and
      Yellow Fever virus. HLA class II restricted T cell cross-reactivity between ZIKV
      and other Flaviviruses infection(s) or vaccination may contribute to protection
      or to enhanced immunopathology. We mapped immunodominant, HLA class II
      restricted, CD4 epitopes from ZIKV Envelope (Env), and Non-structural (NS) NS1,
      NS3 and NS5 antigens in HLA class II transgenic mice. In several cases, ZIKV
      primed CD4 cells responded to homologous sequences from other viruses, including
      DENV1-4, WNV or YFV. However, cross-reactive responses could confer immune
      deviation - the response to the Env DENV4 p1 epitope in HLA-DR1 resulted in IL
      17A immunity, often associated with exacerbated immunopathogenesis. This
      conservation of recognition across Flaviviruses, may encompass protective and/or
      pathogenic components and poses challenges to characterization of ZIKV protective
      immunity.

PMID- 29330427
TI  - Three-Dimensional Speckle Light Self-Healing-Based Imaging System.
AB  - Recently new methodologies for imaging have been achieved making use of multiple
      light scattering. Here we present the self-healing effect using a speckled light
      field. We present an experiment that constitutes a useful application for a three
      dimensional light sheet-based imaging system through an inhomogeneous medium.
      Each layer can be imaged independently of the others. The axial resolution
      basically depends on the coherence length, which can be sub-wavelength and
      controllable. This allows for a simple and direct technique for imaging through
      scattering layers with axial resolution improvement. Our results may find
      applications not only in bio-microscopy systems but also in data transmission.

PMID- 29330426
TI  - Glucose-independent segmental phase angles from multi-frequency bioimpedance
      analysis to discriminate diabetes mellitus.
AB  - We investigated segmental phase angles (PAs) in the four limbs using a multi
      frequency bioimpedance analysis (MF-BIA) technique for noninvasively diagnosing
      diabetes mellitus. We conducted a meal tolerance test (MTT) for 45 diabetic and
      45 control subjects stratified by age, sex and body mass index (BMI). HbA1c and
      the waist-to-hip-circumference ratio (WHR) were measured before meal intake, and
      we measured the glucose levels and MF-BIA PAs 5 times for 2 hours after meal
      intake. We employed a t-test to examine the statistical significance and the area
      under the curve (AUC) of the receiver operating characteristics (ROC) to test the
      classification accuracy using segmental PAs at 5, 50, and 250 kHz. Segmental PAs
      were independent of the HbA1c or glucose levels, or their changes caused by the
      MTT. However, the segmental PAs were good indicators for noninvasively screening
      diabetes In particular, leg PAs in females and arm PAs in males showed best
      classification accuracy (AUC = 0.827 for males, AUC = 0.845 for females). Lastly,
      we introduced the PA at maximum reactance (PAmax), which is independent of
      measurement frequencies and can be obtained from any MF-BIA device using a Cole
      Cole model, thus showing potential as a useful biomarker for diabetes.

PMID- 29330428
TI  - Structural insights into two distinct binding modules for Lys63-linked
      polyubiquitin chains in RNF168.
AB  - The E3 ubiquitin (Ub) ligase RNF168 plays a critical role in the initiation of
      the DNA damage response to double-strand breaks (DSBs). The recruitment of RNF168
      by ubiquitylated targets involves two distinct regions, Ub-dependent DSB
      recruitment module (UDM) 1 and UDM2. Here we report the crystal structures of the
      complex between UDM1 and Lys63-linked diUb (K63-Ub2) and that between the C
      terminally truncated UDM2 (UDM2DeltaC) and K63-Ub2. In both structures, UDM1 and
      UDM2DeltaC fold as a single alpha-helix. Their simultaneous bindings to the
      distal and proximal Ub moieties provide specificity for Lys63-linked Ub chains.
      Structural and biochemical analyses of UDM1 elucidate an Ub-binding mechanism
      between UDM1 and polyubiquitylated targets. Mutations of Ub-interacting residues
      in UDM2 prevent the accumulation of RNF168 to DSB sites in U2OS cells, whereas
      those in UDM1 have little effect, suggesting that the interaction of UDM2 with
      ubiquitylated and polyubiquitylated targets mainly contributes to the RNF168
      recruitment.

PMID- 29330429
TI  - Tissue and serum microRNA profile of oral squamous cell carcinoma patients.
AB  - Head and neck cancer is characterized by malignant tumors arising from the
      epithelium covering the upper aerodigestive tract, and the majority of these
      epithelial malignancies are squamous cell carcinomas (SCCs) of the oral cavity
      (OSCCs). The aim of the current work was to identify miRNAs regulated in OSCC
      cancerous tissue when compared to a healthy adjacent tissue and to verify the
      presence of the same miRNAs in the circulation of these patients. For that serum
      samples and biopsies of healthy and tumor tissues were collected from five
      patients diagnosed with OSCC of the oral cavity, RNA was extracted from these
      samples and microRNAs libraries were prepared and sequenced. A total 255 miRNAs
      were identified in tissue and 381 different miRNAs were identified in serum
      samples. When comparing the miRNA expression between tumor and healthy tissue we
      identified 48 miRNAs (25 down- and 23 up-regulated) that were differentially
      expressed (FDR < 0.05). From these 48 differentially expressed miRNAs in tissue,
      30 miRNAs were also found in the serum of the same patients. hsa-miR-32-5p was up
      regulated in tumor compared to healthy tissue in our study, and was previously
      shown to be up-regulated in the serum of OSCC patients. Therefore, this suggests
      that miRNAs can be used as potential non-invasive biomarkers of OSCC.

PMID- 29330430
TI  - Carbon-doped SnS2 nanostructure as a high-efficiency solar fuel catalyst under
      visible light.
AB  - Photocatalytic formation of hydrocarbons using solar energy via artificial
      photosynthesis is a highly desirable renewable-energy source for replacing
      conventional fossil fuels. Using an L-cysteine-based hydrothermal process, here
      we synthesize a carbon-doped SnS2 (SnS2-C) metal dichalcogenide nanostructure,
      which exhibits a highly active and selective photocatalytic conversion of CO2 to
      hydrocarbons under visible-light. The interstitial carbon doping induced
      microstrain in the SnS2 lattice, resulting in different photophysical properties
      as compared with undoped SnS2. This SnS2-C photocatalyst significantly enhances
      the CO2 reduction activity under visible light, attaining a photochemical quantum
      efficiency of above 0.7%. The SnS2-C photocatalyst represents an important
      contribution towards high quantum efficiency artificial photosynthesis based on
      gas phase photocatalytic CO2 reduction under visible light, where the in situ
      carbon-doped SnS2 nanostructure improves the stability and the light harvesting
      and charge separation efficiency, and significantly enhances the photocatalytic
      activity.

PMID- 29330431
TI  - Gyrotropic Zener tunneling and nonlinear IV curves in the zero-energy Landau
      level of graphene in a strong magnetic field.
AB  - We have investigated tunneling current through a suspended graphene Corbino disk
      in high magnetic fields at the Dirac point, i.e. at filling factor nu = 0. At the
      onset of the dielectric breakdown the current through the disk grows
      exponentially before ohmic behaviour, but in a manner distinct from thermal
      activation. We find that Zener tunneling between Landau sublevels dominates,
      facilitated by tilting of the source-drain bias potential. According to our
      analytic modelling, the Zener tunneling is strongly affected by the gyrotropic
      force (Lorentz force) due to the high magnetic field.

PMID- 29330432
TI  - Developing genome-wide SNPs and constructing an ultrahigh-density linkage map in
      oil palm.
AB  - Oil palm (Elaeis guineensis Jacq.) is the leading oil-producing crops and the
      most important edible oil resource worldwide. DNA markers and genetic linkage
      maps are essential resources for marker-assisted selection to accelerate genetic
      improvement. We conducted RAD-seq on an Illumina NextSeq500 to discover genome
      wide SNPs, and used the SNPs to construct a linkage map for an oil palm (Tenera)
      population derived from a cross between a Deli Dura and an AVROS Pisifera. The
      RAD-seq produced 1,076 million single-end reads across the breeding population
      containing 155 trees. Mining this dataset detected 510,251 loci. After filtering
      out loci with low accuracy and more than 20% missing data, 11,394 SNPs were
      retained. Using these SNPs, in combination with 188 anchor SNPs and 123
      microsatellites, we constructed a linkage map containing 10,023 markers covering
      16 chromosomes. The map length is 2,938.2 cM with an average marker space of 0.29
      cM. The large number of SNPs will supply ample choices of DNA markers in
      analysing the genetic diversity, population structure and evolution of oil palm.
      This high-density linkage map will contribute to mapping quantitative trait loci
      (QTL) for important traits, thus accelerating oil palm genetic improvement.

PMID- 29330434
TI  - Targeting melanoma stem cells with the Vitamin E derivative delta-tocotrienol.
AB  - The prognosis of metastatic melanoma is very poor, due to the development of drug
      resistance. Cancer stem cells (CSCs) may play a crucial role in this mechanism,
      contributing to disease relapse. We first characterized CSCs in melanoma cell
      lines. We observed that A375 (but not BLM) cells are able to form melanospheres
      and show CSCs traits: expression of the pluripotency markers SOX2 and KLF4,
      higher invasiveness and tumor formation capability in vivo with respect to
      parental adherent cells. We also showed that a subpopulation of autofluorescent
      cells expressing the ABCG2 stem cell marker is present in the A375 spheroid
      culture. Based on these data, we investigated whether delta-TT might target
      melanoma CSCs. We demonstrated that melanoma cells escaping the antitumor
      activity of delta-TT are completely devoid of the ability to form melanospheres.
      In contrast, cells that escaped vemurafenib treatment show a higher ability to
      form melanospheres than control cells. delta-TT also induced disaggregation of
      A375 melanospheres and reduced the spheroidogenic ability of sphere-derived
      cells, reducing the expression of the ABCG2 marker. These data demonstrate that
      delta-TT exerts its antitumor activity by targeting the CSC subpopulation of A375
      melanoma cells and might represent a novel chemopreventive/therapeutic strategy
      against melanoma.

PMID- 29330436
TI  - Blood transcriptomics of captive forest musk deer (Moschus berezovskii) and
      possible associations with the immune response to abscesses.
AB  - Forest musk deer (Moschus berezovskii; FMD) are both economically valuable and
      highly endangered. A problem for FMD captive breeding programs has been the
      susceptibility of FMD to abscesses. To investigate the mechanisms of abscess
      development in FMD, the blood transcriptomes of three purulent and three healthy
      individuals were generated. A total of ~39.68 Gb bases were generated using
      Illumina HiSeq 4000 sequencing technology and 77,752 unigenes were identified
      after assembling. All the unigenes were annotated, with 63,531 (81.71%) mapping
      to at least one database. Based on these functional annotations, 45,798 coding
      sequences (CDS) were detected, along with 12,697 simple sequence repeats (SSRs)
      and 65,536 single nucleotide polymorphisms (SNPs). A total of 113 unigenes were
      found to be differentially expressed between healthy and purulent individuals.
      Functional annotation indicated that most of these differentially expressed genes
      were involved in the regulation of immune system processes, particularly those
      associated with parasitic and bacterial infection pathways.

PMID- 29330433
TI  - Effect of atorvastatin on the gut microbiota of high fat diet-induced
      hypercholesterolemic rats.
AB  - The aim of the present study was to investigate alterations in gut microbiota
      associated with hypercholesterolemia and treatment with atorvastatin, a commonly
      prescribed cholesterol-lowering drug. In this study, seven experimental groups of
      rats were developed based on diets [high-fat diet (HFD) and normal chow diet
      (NCD)] and various doses of atorvastatin in HFD and NCD groups. 16S rRNA amplicon
      sequencing was used to analyze the gut microbiota. Atorvastatin significantly
      reduced the cholesterol level in treated rats. Bacterial diversity was decreased
      in the drug-treated NCD group compared to the NCD control, but atorvastatin
      treated HFD groups showed a relative increase in biodiversity compared to HFD
      control group. Atorvastatin promoted the relative abundance of Proteobacteria and
      reduced the abundance of Firmicutes in drug-treated HFD groups. Among the
      dominant taxa in the drug-treated HFD groups, Oscillospira, Parabacteroides,
      Ruminococcus, unclassified CF231, YRC22 (Paraprevotellaceae), and SMB53
      (Clostridiaceae) showed reversion in population distribution toward NCD group
      relative to HFD group. Drug-treated HFD and NCD groups both showed an increased
      relative abundance of Helicobacter. Overall, bacterial community composition was
      altered, and diversity of gut microbiota increased with atorvastatin treatment in
      HFD group. Reversion in relative abundance of specific dominant taxa was observed
      with drug treatment to HFD rats.

PMID- 29330435
TI  - Beta-catenin cleavage enhances transcriptional activation.
AB  - Nuclear activation of Wnt/beta-catenin signaling is required for cell
      proliferation in inflammation and cancer. Studies from our group indicate that
      beta-catenin activation in colitis and colorectal cancer (CRC) correlates with
      increased nuclear levels of beta-catenin phosphorylated at serine 552 (pbeta
      Cat552). Biochemical analysis of nuclear extracts from cancer biopsies revealed
      the existence of low molecular weight (LMW) pbeta-Cat552, increased to the
      exclusion of full size (FS) forms of beta-catenin. LMW beta-catenin lacks both
      termini, leaving residues in the armadillo repeat intact. Further experiments
      showed that TCF4 predominantly binds LMW pbeta-Cat552 in the nucleus of inflamed
      and cancerous cells. Nuclear chromatin bound localization of LMW pbeta-Cat552 was
      blocked in cells by inhibition of proteasomal chymotrypsin-like activity but not
      by other protease inhibitors. K48 polyubiquitinated FS and LMW beta-catenin were
      increased by treatment with bortezomib. Overexpressed in vitro double truncated
      beta-catenin increased transcriptional activity, cell proliferation and growth of
      tumor xenografts compared to FS beta-catenin. Serine 552-> alanin substitution
      abrogated K48 polyubiquitination,  beta-catenin nuclear translocation and tumor
      xenograft growth. These data suggest that a novel proteasome-dependent
      posttranslational modification of beta-catenin enhances transcriptional
      activation. Discovery of this pathway may be helpful in the development of
      diagnostic and therapeutic tools in colitis and cancer.

PMID- 29330437
TI  - A Computational Assay of Estrogen Receptor alpha Antagonists Reveals the Key
      Common Structural Traits of Drugs Effectively Fighting Refractory Breast Cancers.
AB  - Somatic mutations of the Estrogen Receptor alpha (ERalpha) occur with an up to
      40% incidence in ER sensitive breast cancer (BC) patients undergoing prolonged
      endocrine treatments. These polymorphisms are implicated in acquired resistance,
      disease relapse, and increased mortality rates, hence representing a current
      major clinical challenge. Here, multi-microseconds (12.5 us) molecular dynamics
      simulations revealed that recurrent ERalpha polymorphisms (i. e. L536Q, Y537S,
      Y537N, D538G) (mERalpha) are constitutively active in their apo form and that
      they prompt the selection of an agonist (active)-like conformation even upon
      antagonists binding. Interestingly, our simulations rationalize, for the first
      time, the efficacy profile of (pre)clinically used Selective Estrogen Receptor
      Modulators/Downregulators (SERMs/SERDs) against these variants, enlightening, at
      atomistic level of detail, the key common structural traits needed by drugs able
      to effectively fight refractory BC types. This knowledge represents a key
      advancement for mechanism-based therapeutics targeting resistant ERalpha
      isoforms, potentially allowing the community to move a step closer to 'precision
      medicine' calibrated on patients' genetic profiles and disease progression.

PMID- 29330438
TI  - Improved Resolution Optical Time Stretch Imaging Based on High Efficiency In
      Fiber Diffraction.
AB  - Most overlooked challenges in ultrafast optical time stretch imaging (OTSI) are
      sacrificed spatial resolution and higher optical loss. These challenges are
      originated from optical diffraction devices used in OTSI, which encode image into
      spectra of ultrashort optical pulses. Conventional free-space diffraction
      gratings, as widely used in existing OTSI systems, suffer from several inherent
      drawbacks: limited diffraction efficiency in a non-Littrow configuration due to
      inherent zeroth-order reflection, high coupling loss between free-space gratings
      and optical fibers, bulky footprint, and more importantly, sacrificed imaging
      resolution due to non-full-aperture illumination for individual wavelengths. Here
      we report resolution-improved and diffraction-efficient OTSI using in-fiber
      diffraction for the first time to our knowledge. The key to overcome the existing
      challenges is a 45 degrees  tilted fiber grating (TFG), which serves as a compact
      in-fiber diffraction device offering improved diffraction efficiency (up to 97%),
      inherent compatibility with optical fibers, and improved imaging resolution
      owning to almost full-aperture illumination for all illumination wavelengths. 50
      million frames per second imaging of fast moving object at 46 m/s with improved
      imaging resolution has been demonstrated. This conceptually new in-fiber
      diffraction design opens the way towards cost-effective, compact and high
      resolution OTSI systems for image-based high-throughput detection and
      measurement.

PMID- 29330440
TI  - Evidence of s-wave superconductivity in the noncentrosymmetric La7Ir3.
AB  - Superconductivity in noncentrosymmetric compounds has attracted sustained
      interest in the last decades. Here we present a detailed study on the transport,
      thermodynamic properties and the band structure of the noncentrosymmetric
      superconductor La 7 Ir 3 (T c  ~ 2.3 K) that was recently proposed to break the
      time-reversal symmetry. It is found that La7Ir3 displays a moderately large
      electronic heat capacity (Sommerfeld coefficient gamma n  ~ 53.1 mJ/mol K2) and a
      significantly enhanced Kadowaki-Woods ratio (KWR ~32 MUOmega cm mol2 K2 J-2) that
      is greater than the typical value (~10 MUOmega cm mol2 K2 J-2) for strongly
      correlated electron systems. The upper critical field Hc2 was seen to be nicely
      described by the single-band Werthamer-Helfand-Hohenberg model down to very low
      temperatures. The hydrostatic pressure effects on the superconductivity were also
      investigated. The heat capacity below T c reveals a dominant s-wave gap with the
      magnitude close to the BCS value. The first-principles calculations yield the
      electron-phonon coupling constant lambda = 0.81 and the logarithmically averaged
      frequency omega ln  = 78.5 K, resulting in a theoretical T c  = 2.5 K, close to
      the experimental value. Our calculations suggest that the enhanced electronic
      heat capacity is more likely due to electron-phonon coupling, rather than the
      electron-electron correlation effects. Collectively, these results place severe
      constraints on any theory of exotic superconductivity in this system.

PMID- 29330439
TI  - Induction of protein citrullination and auto-antibodies production in murine
      exposed to nickel nanomaterials.
AB  - Citrullination, or the post-translational deimination of polypeptide-bound
      arginine, is involved in several pathological processes in the body, including
      autoimmunity and tumorigenesis. Recent studies have shown that nanomaterials can
      trigger protein citrullination, which might constitute a common pathogenic link
      to disease development. Here we demonstrated auto-antibody production in serum of
      nanomaterials-treated mice. Citrullination-associated phenomena and PAD levels
      were found to be elevated in nanomaterials -treated cell lines as well as in the
      spleen, kidneys and lymph nodes of mice, suggesting a systemic response to
      nanomaterials injection, and validated in human pleural and pericardial malignant
      mesothelioma (MM) samples. The observed systemic responses in mice exposed to
      nanomaterials support the evidence linking exposure to environmental factors with
      the development of autoimmunity responses and reinforces the need for
      comprehensive safety screening of nanomaterials. Furthermore, these nanomaterials
      induce pathological processes that mimic those observed in Pleural MM, and
      therefore require further investigations into their carcinogenicity.

PMID- 29330441
TI  - Pathway design using de novo steps through uncharted biochemical spaces.
AB  - Existing retrosynthesis tools generally traverse production routes from a source
      to a sink metabolite using known enzymes or de novo steps. Generally, important
      considerations such as blending known transformations with putative steps,
      complexity of pathway topology, mass conservation, cofactor balance,
      thermodynamic feasibility, microbial chassis selection, and cost are largely
      dealt with in a posteriori fashion. The computational procedure we present here
      designs bioconversion routes while simultaneously considering any combination of
      the aforementioned design criteria. First, we track and codify as rules all
      reaction centers using a prime factorization-based encoding technique (rePrime).
      Reaction rules and known biotransformations are then simultaneously used by the
      pathway design algorithm (novoStoic) to trace both metabolites and molecular
      moieties through balanced bio-conversion strategies. We demonstrate the use of
      novoStoic in bypassing steps in existing pathways through putative
      transformations, assembling complex pathways blending both known and putative
      steps toward pharmaceuticals, and postulating ways to biodegrade xenobiotics.

PMID- 29330442
TI  - Competition among the attentional networks due to resource reduction in Tibetan
      indigenous residents: evidence from event-related potentials.
AB  - This study used the attention network test (ANT) to evaluate the alerting,
      orienting, and executive network efficiencies of attention related to indigenous
      residents who were born and raised until early adulthood in different high
      altitude areas (2900-m, 3700-m, and 4200-m) at the same location (3700-m) where
      these residents had been living for approximately 2 years in Tibet. We further
      applied the event-related potential (ERP) method to identify the underlying
      neurophysiological basis. Based on the ANT, we found that, in the 4200-m
      residents, executive function was increased but the orienting function was
      decreased, and the executive and orienting network scores were oppositely
      correlated. The behavioral findings were supported by the ERP data, showing that
      the P3 amplitude changes indicated that the executive function was over-active
      under conflict conditions and that the N1 amplitude change indicated a decreased
      orienting function in the 4200-m residents. In addition, the changed P3
      amplitudes were significantly correlated with intelligence performance across the
      residents only in the 4200-m group. The present study provided evidence for
      competition among the attentional networks due to high-altitude exposure in
      indigenous residents, and showed the existence of a threshold of the influence of
      high altitudes on attentional function in the brain.

PMID- 29330443
TI  - An insight into intestinal mucosal microbiota disruption after stroke.
AB  - Recent work from our laboratory has provided evidence that indicates selective
      bacterial translocation from the host gut microbiota to peripheral tissues (i.e.
      lung) plays a key role in the development of post-stroke infections. Despite
      this, it is currently unknown whether mucosal bacteria that live on and interact
      closely with the host intestinal epithelium contribute in regulating bacterial
      translocation after stroke. Here, we found that the microbial communities within
      the mucosa of gastrointestinal tract (GIT) were significantly different between
      sham-operated and post-stroke mice at 24 h following surgery. The differences in
      microbiota composition were substantial in all sections of the GIT and were
      significant, even at the phylum level. The main characteristics of the stroke
      induced shift in mucosal microbiota composition were an increased abundance of
      Akkermansia muciniphila and an excessive abundance of clostridial species.
      Furthermore, we analysed the predicted functional potential of the altered
      mucosal microbiota induced by stroke using PICRUSt and revealed significant
      increases in functions associated with infectious diseases, membrane transport
      and xenobiotic degradation. Our findings revealed stroke induces far-reaching and
      robust changes to the intestinal mucosal microbiota. A better understanding of
      the precise molecular events leading up to stroke-induced mucosal microbiota
      changes may represent novel therapy targets to improve patient outcomes.

PMID- 29330444
TI  - Lidocaine enhances the effects of chemotherapeutic drugs against bladder cancer.
AB  - This study aimed to investigate whether lidocaine, alone or in combination with
      other chemotherapeutic agents, inhibits the growth of human bladder cancer cells
      in vitro and orthotopically transplanted bladder tumors in vivo. The effects of
      lidocaine (1.25, 2.5 or 5 mg/mL), mitomycin C (MMC, 0.66 mg/mL), pirarubicin
      (0.75 mg/mL) and Su Fu'ning lotion (SFN, 0.0625 mg/mL) on the proliferation of
      human bladder cancer (BIU-87) cells were studied using the MTT assay. A Balb/c
      nude mouse model of bladder cancer was developed by orthotopic transplantation of
      BIU-87 cells, and the effects of intravesical instillation of lidocaine and MMC
      on bladder wet weight (a measure of tumor size) and survival (over 60 days) were
      studied. Lidocaine inhibited proliferation of BIU-87 cells in a concentration
      dependent manner and (when given in combination) enhanced the actions of each of
      the other antiproliferative agents. In tumor-bearing mice, MMC alone had no
      effect on mean survival or bladder wet weight. However, the combination of 0.66
      mg/mL MMC and 5 mg/mL lidocaine prolonged survival (from 34.62 +/- 6.49 to 49.30
      +/- 6.72 days; n = 8, P < 0.05) and reduced bladder wet weight (from 68.94 +/-
      53.61 to 20.26 +/- 6.07; n = 8, P < 0.05). Intravesical instillation of lidocaine
      combined with other chemotherapeutic agents potentially could be an effective
      therapy for bladder cancer.

PMID- 29330445
TI  - A novel approach for correction of crosstalk effects in pathway analysis and its
      application in osteoporosis research.
AB  - Osteoporosis is a prevalent bone metabolic disease and peripheral blood monocytes
      represent a major systemic cell type for bone metabolism. To identify the key
      dysfunctional pathways in osteoporosis, we performed pathway analyses on
      microarray data of monocytes from subjects with extremely high/low hip bone
      mineral density. We first performed a traditional pathway analysis for which
      different pathways were treated as independent. However, genes overlap among
      pathways will lead to "crosstalk" phenomenon, which may lead to false
      positive/negative results. Therefore, we applied correction techniques including
      a novel approach that considers the correlation among genes to adjust the
      crosstalk effects in the analysis. In traditional analysis, 10 pathways were
      found to be significantly associated with BMD variation. After correction for
      crosstalk effects, three of them remained significant. Moreover, the MAPK
      signaling pathway, which has been shown to be important for osteoclastogenesis,
      became significant only after the correction for crosstalk effects. We also
      identified a new module mainly consisting of genes present in mitochondria to be
      significant. In summary, we describe a novel method to correct the crosstalk
      effect in pathway analysis and found five key independent pathways involved in
      BMD regulation, which may provide a better understanding of biological functional
      networks in osteoporosis.

PMID- 29330446
TI  - Effect of puerarin in promoting fatty acid oxidation by increasing mitochondrial
      oxidative capacity and biogenesis in skeletal muscle in diabetic rats.
AB  - BACKGROUND: Type 2 diabetes is characterized by dyslipidemia and the accumulation
      of lipids in non-adipose tissue, including skeletal muscle. Puerarin, which is a
      natural isoflavonoid isolated from the root of the plant Pueraria lobata, has
      been shown to have antidiabetic activity. However, the lipid-reducing effect of
      puerarin, in particular in skeletal muscle, has not yet been addressed. METHODS:
      We examined the effect of puerarin on mitochondrial function and the oxidation of
      fatty acids in the skeletal muscle of high-fat diet/streptozotocin-induced
      diabetic rats. RESULTS: Puerarin effectively alleviated dyslipidemia and
      decreased the accumulation of intramyocellular lipids by upregulating the
      expression of a range of genes involved in mitochondrial biogenesis, oxidative
      phosphorylation, the detoxification of reactive oxygen species, and the oxidation
      of fatty acids in the muscle of diabetic rats. Also, the effect of puerarin on
      mitochondrial biogenesis might partially involve the function of the MU-opioid
      receptor. In addition, puerarin decreased the trafficking of fatty acid
      translocase/CD36 to the plasma membrane to reduce the uptake of fatty acids by
      myocytes. In vitro studies confirmed that puerarin acted directly on muscle cells
      to promote the oxidation of fatty acids in insulin-resistant myotubes treated
      with palmitate. CONCLUSIONS: Puerarin improved the performance of mitochondria in
      muscle and promoted the oxidation of fatty acids, which thus prevented the
      accumulation of intramyocellular lipids in diabetic rats. Our findings will be
      beneficial both for elucidating the mechanism of the antidiabetic activity of
      puerarin and for promoting the therapeutic potential of puerarin in the treatment
      of diabetes.

PMID- 29330447
TI  - Human Placental-Derived Adherent Stromal Cells Co-Induced with TNF-alpha and IFN
      gamma Inhibit Triple-Negative Breast Cancer in Nude Mouse Xenograft Models.
AB  - Culturing 3D-expanded human placental-derived adherent stromal cells (ASCs) in
      the presence of tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN
      gamma) transiently upregulated the secretion of numerous anti-proliferative, anti
      angiogenic and pro-inflammatory cytokines. In a 3D-spheroid screening assay,
      conditioned medium from these induced-ASCs inhibited proliferation of cancer cell
      lines, including triple-negative breast cancer (TNBC) lines. In vitro co-culture
      studies of induced-ASCs with MDA-MB-231 human breast carcinoma cells, a model
      representing TNBC, supports a mechanism involving immunomodulation and
      angiogenesis inhibition. In vivo studies in nude mice showed that intramuscular
      administration of induced-ASCs halted MDA-MB-231 cell proliferation, and
      inhibited tumor progression and vascularization. Thirty percent of treated mice
      experienced complete tumor remission. Murine serum concentrations of the tumor
      supporting cytokines Interleukin-6 (IL-6), Vascular endothelial growth factor
      (VEGF) and Granulocyte-colony stimulating factor (G-CSF) were lowered to naive
      levels. A somatic mutation analysis identified numerous genes which could be
      screened in patients to increase a positive therapeutic outcome. Taken together,
      these results show that targeted changes in the secretion profile of ASCs may
      improve their therapeutic potential.

PMID- 29330449
TI  - Lithium chloride effectively kills the honey bee parasite Varroa destructor by a
      systemic mode of action.
AB  - Honey bees are increasingly important in the pollination of crops and wild
      plants. Recent reports of the weakening and periodical high losses of managed
      honey bee colonies have alarmed beekeeper, farmers and scientists. Infestations
      with the ectoparasitic mite Varroa destructor in combination with its associated
      viruses have been identified as a crucial driver of these health problems.
      Although yearly treatments are required to prevent collapses of honey bee
      colonies, the number of effective acaricides is small and no new active compounds
      have been registered in the past 25 years. RNAi-based methods were proposed
      recently as a promising new tool. However, the application of these methods
      according to published protocols has led to a surprising discovery. Here, we show
      that the lithium chloride that was used to precipitate RNA and other lithium
      compounds is highly effective at killing Varroa mites when fed to host bees at
      low millimolar concentrations. Experiments with caged bees and brood-free
      artificial swarms consisting of a queen and several thousand bees clearly
      demonstrate the potential of lithium as miticidal agent with good tolerability in
      worker bees providing a promising basis for the development of an effective and
      easy-to-apply control method for mite treatment.

PMID- 29330452
TI  - Assessment of the responses of soil pore properties to combined soil structure
      amendments using X-ray computed tomography.
AB  - Soil amendments, such as straw mulch, organic fertilizers and superabsorbent
      polymer (SAP), are extensively applied to improve soil structure and porosity,
      and we reported the functional consequences of the individual application of
      these amendments in our previous study. However, whether combined amendments are
      more effective than their individual applications for improving soil pore
      structure is unknown. Here, we conducted X-ray computed tomography (CT) scanning
      on undisturbed soil columns to investigate the efficiency of two-amendment
      application, including straw mulch and organic manure, SAP and organic manure, or
      SAP and straw mulch, for improving soil pore properties and pore distribution.
      The X-ray CT technique allows us to accurately determine the number, morphology,
      and location of macropores (>1 mm in diameter) and smaller pores (0.13-1.0 mm).
      Compared to the control treatment, which showed the lowest increase in soil
      porosity, all the combined treatments led to an increase in the numbers of both
      macropores and smaller soil pores, causing a significant improvement in soil
      structure and porosity. Among these treatments, the application of both straw
      mulch and organic manure was the most effective for improving soil porosity and
      soil physical structure.

PMID- 29330450
TI  - C-terminal short arginine/serine repeat sequence-dependent regulation of Y14
      (RBM8A) localization.
AB  - Y14 (RBM8A) is an RNA recognition motif-containing protein that forms
      heterodimers with MAGOH and serves as a core factor of the RNA surveillance
      machinery for the exon junction complex (EJC). The role of the Y14 C-terminal
      serine/arginine (RS) repeat-containing region, which has been reported to undergo
      modifications such as phosphorylation and methylation, has not been sufficiently
      investigated. Thus, we aimed to explore the functional significance of the Y14 C
      terminal region. Deletion or dephosphorylation mimic mutants of the C-terminal
      region showed a shift in localization from the nucleoplasmic region; in addition,
      the C-terminal RS repeat-containing sequence itself exhibited the potential for
      nucleolar localization. Additionally, the regulation of Y14 localization by the C
      terminal region was further found to be exquisitely controlled by MAGOH binding.
      Cumulatively, our findings, which demonstrated that Y14 localization is regulated
      not only by the previously reported N-terminal localization signal but also by
      the C-terminal RS repeat-containing region through phosphorylation and MAGOH
      binding to Y14, provide new insights for the mechanism of localization of short
      RS repeat-containing proteins.

PMID- 29330448
TI  - Visual field loss and vision-related quality of life in the Italian Primary Open
      Angle Glaucoma Study.
AB  - The aim of this study was to examine the relationship between visual field (VF)
      loss, vision-related quality of life (QoL) and glaucoma-related symptoms in a
      large cohort of primary open angle glaucoma (POAG) patients. POAG patients with
      or without VF defects or "glaucoma suspect" patients were considered eligible.
      QoL was assessed using the validated versions of the 25-item National Eye
      Institute Visual Function Questionnaire (NEI-VFQ-25) and glaucoma-related
      symptoms were assessed using the Glaucoma Symptom Scale (GSS). Patients were
      classified as having VF damage in one eye (VFD-1), both eyes (VFD-2), or neither
      eye (VFD-0). 3227 patients were enrolled and 2940 were eligible for the analysis.
      13.4% of patients were classified in the VFD-0, 23.7% in the VFD-1, and 62.9% in
      the VFD-2 group. GSS visual symptoms domain (Func-4) and GSS non-visual symptoms
      domain (Symp-6) scores were similar for the VFD-0 and VFD-1 groups (p = 0.133 and
      p = 0.834 for Func-4 and Symp-6, respectively). VFD-0 group had higher scores
      than VFD-2 both in Func-4 (p < 0.001) and Symp-6 domains (p = 0.035). Regarding
      the NEI-VFQ-25, our data demonstrated that bilateral VF defects are associated
      with vision-related QoL deterioration, irrespective of visual acuity.

PMID- 29330451
TI  - Tracheophyte genomes keep track of the deep evolution of the Caulimoviridae.
AB  - Endogenous viral elements (EVEs) are viral sequences that are integrated in the
      nuclear genomes of their hosts and are signatures of viral infections that may
      have occurred millions of years ago. The study of EVEs, coined paleovirology,
      provides important insights into virus evolution. The Caulimoviridae is the most
      common group of EVEs in plants, although their presence has often been overlooked
      in plant genome studies. We have refined methods for the identification of
      caulimovirid EVEs and interrogated the genomes of a broad diversity of plant
      taxa, from algae to advanced flowering plants. Evidence is provided that almost
      every vascular plant (tracheophyte), including the most primitive taxa
      (clubmosses, ferns and gymnosperms) contains caulimovirid EVEs, many of which
      represent previously unrecognized evolutionary branches. In angiosperms, EVEs
      from at least one and as many as five different caulimovirid genera were
      frequently detected, and florendoviruses were the most widely distributed,
      followed by petuviruses. From the analysis of the distribution of different
      caulimovirid genera within different plant species, we propose a working
      evolutionary scenario in which this family of viruses emerged at latest during
      Devonian era (approx. 320 million years ago) followed by vertical transmission
      and by several cross-division host swaps.

PMID- 29330453
TI  - Calcium sulfate induced versus PMMA-induced membrane in a critical-sized femoral
      defect in a rat model.
AB  - Aimed to investigate the characteristics of CS-induced membrane in comparison
      with the PMMA-induced membrane. Cellular components, histological changes, growth
      factor expressions of IL-6, VEGF, BMP-2, and TGF-beta1 in the two induced
      membranes were compared at 2, 4, 6 and 8 weeks, respectively. We also compared
      the histological changes at the bone defects between CS and PMMA groups. The
      structural characteristics of induced membrane were similar between CS and PMMA.
      Endochondral ossification took place in the CS-induced membrane at 8 week. Levels
      of VEGF, BMP-2 and TGF-beta1 in CS-induced membrane were insignificantly higher
      than those in PMMA-induced membrane at different time points. The expression of
      IL-6 was significantly higher in PMMA-induced membranes at 2nd week. In addition,
      osteogenic and neovascular activities of induced membranes increased with time
      and peaked at 6 weeks. CS promoted endochondral ossification at the broken ends
      of the bone defect than PMMA did. CS-induced membrane has a better capacity of
      generating VEGF, BMP-2 and TGF-beta1.osteogenic and neovascular activities
      achieve highest level at 6 week. CS may have the potential to replace PMMA as a
      novel spacer in Masquelet technique.

PMID- 29330454
TI  - Dynamic malaria hotspots in an open cohort in western Kenya.
AB  - Malaria hotspots, defined as areas where transmission intensity exceeds the
      average level, become more pronounced as transmission declines. Targeting
      hotspots may accelerate reductions in transmission and could be pivotal for
      malaria elimination. Determinants of hotspot location, particularly of their
      movement, are poorly understood. We used spatial statistical methods to identify
      foci of incidence of self-reported malaria in a large census population of 64,000
      people, in 8,290 compounds over a 2.5-year study period. Regression models
      examine stability of hotspots and identify static and dynamic correlates with
      their location. Hotspot location changed over short time-periods, rarely
      recurring in the same area. Hotspots identified in spring versus fall season
      differed in their stability. Households located in a hotspot in the fall were
      more likely to be located in a hotspot the following fall (RR = 1.77, 95% CI:
      1.66-1.89), but the opposite was true for compounds in spring hotspots (RR =
      0.15, 95% CI: 0.08-0.28). Location within a hotspot was related to environmental
      and static household characteristics such as distance to roads or rivers. Human
      migration into a household was correlated with risk of hotspot membership, but
      the direction of the association differed based on the origin of the migration
      event.

PMID- 29330455
TI  - Towards Electrotuneable Nanoplasmonic Fabry-Perot Interferometer.
AB  - Directed voltage-controlled assembly and disassembly of plasmonic nanoparticles
      (NPs) at electrified solid-electrolyte interfaces (SEI) offer novel opportunities
      for the creation of tuneable optical devices. We apply this concept to propose a
      fast electrotuneable, NP-based Fabry-Perot (FP) interferometer, comprising two
      parallel transparent electrodes in aqueous electrolyte, which form the
      polarizable SEI for directed assembly-disassembly of negatively charged NPs. An
      FP cavity between two reflective NP-monolayers assembled at such interfaces can
      be formed or deconstructed under positive or negative polarization of the
      electrodes, respectively. The inter-NP spacing may be tuned via applied
      potential. Since the intensity, wavelength, and linewidth of the reflectivity
      peak depend on the NP packing density, the transmission spectrum of the system
      can thus be varied. A detailed theoretical model of the system's optical response
      is presented, which shows excellent agreement with full-wave simulations. The
      tuning of the peak transmission wavelength and linewidth is investigated in
      detail. Design guidelines for such NP-based FP systems are established, where
      transmission characteristics can be electrotuned in-situ, without mechanically
      altering the cavity length.

PMID- 29330456
TI  - 20-HETE promotes glucose-stimulated insulin secretion in an autocrine manner
      through FFAR1.
AB  - The long-chain fatty acid receptor FFAR1 is highly expressed in pancreatic beta
      cells. Synthetic FFAR1 agonists can be used as antidiabetic drugs to promote
      glucose-stimulated insulin secretion (GSIS). However, the physiological role of
      FFAR1 in beta-cells remains poorly understood. Here we show that 20-HETE
      activates FFAR1 and promotes GSIS via FFAR1 with higher potency and efficacy than
      dietary fatty acids such as palmitic, linoleic, and alpha-linolenic acid. Murine
      and human beta-cells produce 20-HETE, and the omega-hydroxylase-mediated
      formation and release of 20-HETE is strongly stimulated by glucose.
      Pharmacological inhibition of 20-HETE formation and blockade of FFAR1 in islets
      inhibits GSIS. In islets from type-2 diabetic humans and mice, glucose-stimulated
      20-HETE formation and 20-HETE-dependent stimulation of GSIS are strongly reduced.
      We show that 20-HETE is an FFAR1 agonist, which functions as an autocrine
      positive feed-forward regulator of GSIS, and that a reduced glucose-induced 20
      HETE formation contributes to inefficient GSIS in type-2 diabetes.

PMID- 29330457
TI  - Spatially selective responses to Kanizsa and occlusion stimuli in human visual
      cortex.
AB  - Early visual cortex responds to illusory contours in which abutting lines or
      collinear edges imply the presence of an occluding surface, as well as to
      occluded parts of an object. Here we used functional magnetic resonance imaging
      (fMRI) and population receptive field (pRF) analysis to map retinotopic responses
      in early visual cortex using bar stimuli defined by illusory contours, occluded
      parts of a bar, or subtle luminance contrast. All conditions produced retinotopic
      responses in early visual field maps even though signal-to-noise ratios were very
      low. We found that signal-to-noise ratios and coherence with independent high
      contrast mapping data increased from V1 to V2 to V3. Moreover, we found no
      differences of signal-to-noise ratios or pRF sizes between the low-contrast
      luminance and illusion conditions. We propose that all three conditions mapped
      spatial attention to the bar location rather than activations specifically
      related to illusory contours or occlusion.

PMID- 29330458
TI  - Architecture of a mammalian glomerular domain revealed by novel volume
      electroporation using nanoengineered microelectrodes.
AB  - Dense microcircuit reconstruction techniques have begun to provide ultrafine
      insight into the architecture of small-scale networks. However, identifying the
      totality of cells belonging to such neuronal modules, the "inputs" and "outputs,"
      remains a major challenge. Here, we present the development of nanoengineered
      electroporation microelectrodes (NEMs) for comprehensive manipulation of a
      substantial volume of neuronal tissue. Combining finite element modeling and
      focused ion beam milling, NEMs permit substantially higher stimulation
      intensities compared to conventional glass capillaries, allowing for larger
      volumes configurable to the geometry of the target circuit. We apply NEMs to
      achieve near-complete labeling of the neuronal network associated with a
      genetically identified olfactory glomerulus. This allows us to detect sparse
      higher-order features of the wiring architecture that are inaccessible to
      statistical labeling approaches. Thus, NEM labeling provides crucial
      complementary information to dense circuit reconstruction techniques. Relying
      solely on targeting an electrode to the region of interest and passive
      biophysical properties largely common across cell types, this can easily be
      employed anywhere in the CNS.

PMID- 29330459
TI  - A Novel Ultra-Stable, Monomeric Green Fluorescent Protein For Direct Volumetric
      Imaging of Whole Organs Using CLARITY.
AB  - Recent advances in thick tissue clearing are enabling high resolution, volumetric
      fluorescence imaging of complex cellular networks. Fluorescent proteins (FPs)
      such as GFP, however, can be inactivated by the denaturing chemicals used to
      remove lipids in some tissue clearing methods. Here, we solved the crystal
      structure of a recently engineered ultra-stable GFP (usGFP) and propose that the
      two stabilising mutations, Q69L and N164Y, act to improve hydrophobic packing in
      the core of the protein and facilitate hydrogen bonding networks at the surface,
      respectively. usGFP was found to dimerise strongly, which is not desirable for
      some applications. A point mutation at the dimer interface, F223D, generated
      monomeric usGFP (muGFP). Neurons in whole mouse brains were virally transduced
      with either EGFP or muGFP and subjected to Clear Lipid-exchanged Acrylamide
      hybridized Rigid Imaging/Immunostaining/In situ hybridization-compatible Tissue
      hYdrogel (CLARITY) clearing. muGFP fluorescence was retained after CLARITY
      whereas EGFP fluorescence was highly attenuated, thus demonstrating muGFP is a
      novel FP suitable for applications where high fluorescence stability and minimal
      self-association are required.

PMID- 29330461
TI  - Comparing olive oil and C4-dietary oil, a prodrug for the GPR119 agonist, 2
      oleoyl glycerol, less energy intake of the latter is needed to stimulate incretin
      hormone secretion in overweight subjects with type 2 diabetes.
AB  - BACKGROUND/OBJECTIVE: After digestion, dietary triacylglycerol stimulates
      incretin release in humans, mainly through generation of 2-monoacylglycerol, an
      agonist for the intestinal G protein-coupled receptor 119 (GPR119). Enhanced
      incretin release may have beneficial metabolic effects. However, dietary fat may
      promote weight gain and should therefore be restricted in obesity. We designed C4
      dietary oil (1,3-di-butyryl-2-oleoyl glycerol) as a 2-oleoyl glycerol (2-OG)
      generating fat type, which would stimulate incretin release to the same extent
      while providing less calories than equimolar amounts of common triglycerides,
      e.g., olive oil. SUBJECTS AND METHODS: We studied the effect over 180 min of (a)
      19 g olive oil plus 200 g carrot, (b) 10.7 g C4 dietary oil plus 200 g carrot and
      (c) 200 g carrot, respectively, on plasma responses of gut and pancreatic
      hormones in 13 overweight patients with type 2 diabetes (T2D). Theoretically,
      both oil meals result in formation of 7.7 g 2-OG during digestion. RESULTS: Both
      olive oil and C4-dietary oil resulted in greater postprandial (P <= 0.01)
      glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide
      (GIP) responses (incremental area under curve (iAUC)): iAUCGLP-1: 645 +/- 194 and
      702 +/- 97 pM * min; iAUCGIP: 4,338 +/- 764 and 2,894 +/- 601 pM * min) compared
      to the carrot meal (iAUCGLP-1: 7 +/- 103 pM * min; iAUCGIP: 266 +/- 234 pM *
      min). iAUC for GLP-1 and GIP were similar for C4-dietary oil and olive oil,
      although olive oil resulted in a higher peak value for GIP than C4-dietary oil.
      CONCLUSION: C4-dietary oil enhanced secretion of GLP-1 and GIP to almost the same
      extent as olive oil, in spite of liberation of both 2-OG and oleic acid, which
      also may stimulate incretin secretion, from olive oil. Thus, C4-dietary oil is
      more effective as incretin releaser than olive oil per unit of energy and may be
      useful for dietary intervention.

PMID- 29330460
TI  - Enhanced skeletal muscle ribosome biogenesis, yet attenuated mTORC1 and ribosome
      biogenesis-related signalling, following short-term concurrent versus single-mode
      resistance training.
AB  - Combining endurance training with resistance training (RT) may attenuate skeletal
      muscle hypertrophic adaptation versus RT alone; however, the underlying
      mechanisms are unclear. We investigated changes in markers of ribosome
      biogenesis, a process linked with skeletal muscle hypertrophy, following
      concurrent training versus RT alone. Twenty-three males underwent eight weeks of
      RT, either performed alone (RT group, n = 8), or combined with either high
      intensity interval training (HIT+RT group, n = 8), or moderate-intensity
      continuous training (MICT+RT group, n = 7). Muscle samples (vastus lateralis)
      were obtained before training, and immediately before, 1 h and 3 h after the
      final training session. Training-induced changes in basal expression of the 45S
      ribosomal RNA (rRNA) precursor (45S pre-rRNA), and 5.8S and 28S mature rRNAs,
      were greater with concurrent training versus RT. However, during the final
      training session, RT further increased both mTORC1 (p70S6K1 and rps6
      phosphorylation) and 45S pre-rRNA transcription-related signalling (TIF-1A and
      UBF phosphorylation) versus concurrent training. These data suggest that when
      performed in a training-accustomed state, RT induces further increases mTORC1 and
      ribosome biogenesis-related signalling in human skeletal muscle versus concurrent
      training; however, changes in ribosome biogenesis markers were more favourable
      following a period of short-term concurrent training versus RT performed alone.

PMID- 29330462
TI  - miR-143-3p inhibits the proliferation, migration and invasion in osteosarcoma by
      targeting FOSL2.
AB  - Osteosarcoma (OS) is the most common type of primary malignant bone tumor and
      mainly occurs in children and adolescent. Because of its early migration and
      invasion, OS has a poor prognosis. It has been reported that mircoRNAs (miRNAs)
      play a crucial role in the occurrence and development of multiple tumors. In this
      study, we identified the aberrant-expression of miR-143-3p in osteosarcoma and
      examined the role of miR-143-3p in OS development. Further, we searched the miR
      143-3p target gene and verified its accuracy by luciferase experiments. Finally,
      we explored the relationship between miR-143-3p and FOS-Like antigen 2 (FOSL2).
      Our data indicated that miR-143-3p expression was substantially lower in OS
      tissues and cell-line compared with normal tissues, and was lower in patients
      with poor prognosis. In addition miR-143-3p inhibited OS cell proliferation and
      metastasis while promoting apoptosis. We next showed that FOSL2 was directly
      targeted by miR-143-3p and could reverse the inhibition caused by miR-143-3p.
      Finally, we found FOSL2 expression in OS cells was significantly higher compared
      with normal cells and negatively correlated with miR-143-3p. Thus, miR-143-3p
      directly and negatively targets FOSL2 to affect OS characteristics. This provides
      a new target for the treatment of OS and deserves further study.

PMID- 29330463
TI  - Effective photo-enhancement of cellular activity of fluorophore-octaarginine
      antisense PNA conjugates correlates with singlet oxygen formation, endosomal
      escape and chromophore lipophilicity.
AB  - Photochemical internalization (PCI) is a cellular drug delivery method based on
      the generation of light-induced reactive oxygen species (ROS) causing damage to
      the endosomal membrane and thereby resulting in drug release to the cytoplasm. In
      our study a series of antisense fluorophore octaarginine peptide nucleic acid
      (PNA) conjugates were investigated in terms of PCI assisted cellular activity. It
      is found that tetramethylrhodamine and Alexa Fluor 555 conjugated octaarginine
      PNA upon irradiation exhibit more than ten-fold increase in antisense activity in
      the HeLa pLuc705 luciferase splice correction assay. An analogous fluorescein
      conjugate did not show any significant enhancement due to photobleaching, and
      neither did an Alexa Fluor 488 conjugate. Using fluorescence microscopy a
      correlation between endosomal escape and antisense activity was demonstrated, and
      in parallel a correlation to localized formation of ROS assigned primarily to
      singlet oxygen was also observed. The results show that tetramethylrhodamine (and
      to lesser extent Alexa Fluor 555) conjugated octaarginine PNAs are as effectively
      delivered to the cytosol compartment by PCI as by chloroquine assisted delivery
      and also indicate that efficient photodynamic endosomal escape is strongly
      dependent on the quantum yield for photochemical singlet oxygen formation,
      photostability as well as the lipophilicity of the chromophore.

PMID- 29330465
TI  - Insulin Resistance is Associated with Cognitive Decline Among Older Koreans with
      Normal Baseline Cognitive Function: A Prospective Community-Based Cohort Study.
AB  - We evaluated whether metabolic factors were associated with cognitive decline,
      compared to baseline cognitive function, among geriatric population. The present
      study evaluated data from an ongoing prospective community-based Korean cohort
      study. Among 1,387 participants who were >65 years old, 422 participants were
      evaluated using the Korean mini-mental status examination (K-MMSE) at the
      baseline and follow-up examinations. The mean age at the baseline was 69.3 +/-
      2.9 years, and 222 participants (52.6%) were men. The mean duration of education
      was 7.1 +/- 3.6 years. During a mean follow-up of 5.9 +/- 0.1 years, the K-MMSE
      score significantly decreased (-1.1 +/- 2.7 scores), although no significant
      change was observed in the homeostasis model assessment of insulin resistance
      (HOMA-IR) value. Participants with more decreased percent changes in K-MMSE
      scores had a shorter duration of education (p = 0.001), older age (p = 0.022),
      higher baseline K-MMSE score (p < 0.001), and increased insulin resistance (?HOMA
      IR, p = 0.002). The correlation between the percent changes in K-MMSE and ?HOMA
      IR values remained significant after multivariable adjustment (B = -0.201, p =
      0.002). During a 6-year follow-up of older Koreans with normal baseline cognitive
      function, increased insulin resistance was significantly correlated with
      decreased cognitive function.

PMID- 29330464
TI  - Eltrombopag versus romiplostim in treatment of children with persistent or
      chronic immune thrombocytopenia: a systematic review incorporating an indirect
      comparison meta-analysis.
AB  - In absence of direct comparison, we conducted an indirect-comparison meta
      analysis to evaluate the efficacy and safety of thrombopoietin-receptor
      agonists(TPO-RAs) in treatment of pediatric persistent or chronic immune
      thrombocytopenia(ITP). PubMed, Embase, Cochrane Library, Clinical Trials.gov,
      China National Knowledge Infrastructure, and Chinese Biomedical Literature
      Database were searched from their earliest records to May 2017. Randomized
      controlled trials comparing the TPO-RAs with placebo in pediatric ITP were
      included. Outcomes included overall response rate(primary), durable response,
      overall or clinically significant bleeding, the proportion of patients receiving
      rescue medication, and safety. Five randomized placebo-controlled studies(N =
      261) were analyzed. The overall response[Risk Ratio(RR) 0.57, 95% confidence
      interval(CI) 0.21-1.56], the incidence of adverse events (RR 0.96, 95%CI 0.66
      1.39), durable response(RR 2.48, 95%CI 0.31-19.97), and the proportion of
      patients receiving rescue treatment(RR 0.73, 95%CI 0.20-2.73) were similar
      between eltrombopag and romiplostim group. Nevertheless, eltrombopag might have
      lower risk of overall bleeding(RR 0.43, 95%CI 0.23-0.80) and clinically
      significant bleeding(RR 0.33, 95%CI 0.12-0.89) than romiplostim. This meta
      analysis suggests that eltrombopag might be similar to romiplostim in efficacy
      and safety, but seems to reduce the risk of bleeding compared to romiplostim.
      Furthermore, cost of the treatment, comorbidity of patients and drug compliance
      should also be considered in clinical decision making.

PMID- 29330466
TI  - Target engagement imaging of PARP inhibitors in small-cell lung cancer.
AB  - Insufficient chemotherapy response and rapid disease progression remain concerns
      for small-cell lung cancer (SCLC). Oncologists rely on serial CT scanning to
      guide treatment decisions, but this cannot assess in vivo target engagement of
      therapeutic agents. Biomarker assessments in biopsy material do not assess
      contemporaneous target expression, intratumoral drug exposure, or drug-target
      engagement. Here, we report the use of PARP1/2-targeted imaging to measure target
      engagement of PARP inhibitors in vivo. Using a panel of clinical PARP inhibitors,
      we show that PARP imaging can quantify target engagement of chemically diverse
      small molecule inhibitors in vitro and in vivo. We measure PARP1/2 inhibition
      over time to calculate effective doses for individual drugs. Using patient
      derived xenografts, we demonstrate that different therapeutics achieve similar
      integrated inhibition efficiencies under different dosing regimens. This imaging
      approach to non-invasive, quantitative assessment of dynamic intratumoral target
      inhibition may improve patient care through real-time monitoring of drug
      delivery.

PMID- 29330467
TI  - Evidence for sparse synergies in grasping actions.
AB  - Converging evidence shows that hand-actions are controlled at the level of
      synergies and not single muscles. One intriguing aspect of synergy-based action
      representation is that it may be intrinsically sparse and the same synergies can
      be shared across several distinct types of hand-actions. Here, adopting a
      normative angle, we consider three hypotheses for hand-action optimal-control:
      sparse-combination hypothesis (SC) - sparsity in the mapping between synergies
      and actions - i.e., actions implemented using a sparse combination of synergies;
      sparse-elements hypothesis (SE) - sparsity in synergy representation - i.e., the
      mapping between degrees-of-freedom (DoF) and synergies is sparse; double-sparsity
      hypothesis (DS) - a novel view combining both SC and SE - i.e., both the mapping
      between DoF and synergies and between synergies and actions are sparse, each
      action implementing a sparse combination of synergies (as in SC), each using a
      limited set of DoFs (as in SE). We evaluate these hypotheses using hand kinematic
      data from six human subjects performing nine different types of reach-to-grasp
      actions. Our results support DS, suggesting that the best action representation
      is based on a relatively large set of synergies, each involving a reduced number
      of degrees-of-freedom, and that distinct sets of synergies may be involved in
      distinct tasks.

PMID- 29330468
TI  - Alteration in yield and oil quality traits of winter rapeseed by lodging at
      different planting density and nitrogen rates.
AB  - Lodging is a factor that negatively affects yield, seed quality, and harvest
      ability in winter rapeseed (Brassica napus L.). In this study, we quantified the
      lodging-induced yield losses, changes in fatty acid composition, and oil quality
      in rapeseed under different nitrogen application rates and planting densities.
      Field experiments were conducted in 2014-2017 for studying the effect of manually
      induced lodging angles (0 degrees , 30 degrees , 60 degrees , and 90 degrees ),
      10, 20 and 30 d post-flowering at different densities and nitrogen application
      rates. The fertilization/planting density combination N270D45 produced the
      maximum observed yield and seed quality. Timing and angle of lodging had
      significant effects on yield. Lodging at 90 degrees  induced at 10 d post
      flowering caused the maximum reduction in yield, biomass, and silique
      photosynthesis. Seed yield losses were higher at high N application rates, the
      maximum being at N360D45. Lodging decreased seed oil content and altered its
      fatty acid composition by increasing stearic and palmitic acid content, while
      decreasing linoleic and linolenic acid content, and deteriorating oil quality by
      increasing erucic acid and glucosinolate content. Therefore, lodging-induced
      yield loss and reduction in oil content might be reduced by selecting optimum N
      level and planting density.

PMID- 29330470
TI  - beta-Ecdysterone protects SH-SY5Y cells against beta-amyloid-induced apoptosis
      via c-Jun N-terminal kinase- and Akt-associated complementary pathways.
AB  - Recently, the significantly higher incidence of Alzheimer's disease (AD) in women
      than in men has been attributed to the loss of neuroprotective estrogen after
      menopause. Does phytoestrogen have the ability to protect against amyloid-beta
      (Abeta) toxicity? The aim of this study was to evaluate hypothesis that beta
      ecdysterone (beta-Ecd) protects SH-SY5Y cells from Abeta-induced apoptosis by
      separate signaling pathways involving protein kinase B (Akt) and c-Jun N-terminal
      kinase (JNK). Here, we demonstrate that phytoestrogen beta-Ecd inhibits Abeta
      triggered mitochondrial apoptotic pathway, as indicated by Bcl-2/Bax ratio
      elevation, cytochrome c (cyt c) release reduction, and caspase-9 inactivation.
      Interestingly, beta-Ecd upregulates Bcl-2 expression in SH-SY5Y cells under both
      basal and Abeta-challenged conditions, but downregulates Bax expression only in
      Abeta-challenged conditions. Subsequently, Akt-dependent NF-kappaB activation is
      required for Bcl-2 upregulation, but not Bax downregulation, in response to beta
      Ecd, which was validated by the use of LY294002 and Bay11-7082. Notably, beta-Ecd
      attenuates the Abeta-evoked reactive oxygen species (ROS) production, apoptosis
      signal-regulating kinase 1 (ASK1) phosphorylation and JNK activation without
      altering the basal ASK1 phosphorylation and JNK activation. ROS-scavenging by
      diphenyleneiodonium (DPI) abrogated the ability of beta-Ecd to alter the
      activation of ASK1. Simultaneously, inhibition of JNK by SP600125 abolished beta
      Ecd-induced Bax downregulation in Abeta-challenged SH-SY5Y cells, whereas
      LY294002 failed to do so. Consequently, beta-Ecd possesses neuroprotection by
      different and complementary pathways, which together promote a Bcl-2/Bax ratio.
      These data support our hypothesis and suggest that beta-Ecd is a promising
      candidate for the treatment of AD.

PMID- 29330469
TI  - Mycobacterium tuberculosis Exploits a Molecular Off Switch of the Immune System
      for Intracellular Survival.
AB  - Mycobacterium tuberculosis (M. tuberculosis) survives and multiplies inside human
      macrophages by subversion of immune mechanisms. Although these immune evasion
      strategies are well characterised functionally, the underlying molecular
      mechanisms are poorly understood. Here we show that during infection of human
      whole blood with M. tuberculosis, host gene transcriptional suppression, rather
      than activation, is the predominant response. Spatial, temporal and functional
      characterisation of repressed genes revealed their involvement in pathogen
      sensing and phagocytosis, degradation within the phagolysosome and antigen
      processing and presentation. To identify mechanisms underlying suppression of
      multiple immune genes we undertook epigenetic analyses. We identified
      significantly differentially expressed microRNAs with known targets in suppressed
      genes. In addition, after searching regions upstream of the start of
      transcription of suppressed genes for common sequence motifs, we discovered novel
      enriched composite sequence patterns, which corresponded to Alu repeat elements,
      transposable elements known to have wide ranging influences on gene expression.
      Our findings suggest that to survive within infected cells, mycobacteria exploit
      a complex immune "molecular off switch" controlled by both microRNAs and Alu
      regulatory elements.

PMID- 29330471
TI  - SLC26A3 (DRA) prevents TNF-alpha-induced barrier dysfunction and dextran sulfate
      sodium-induced acute colitis.
AB  - SLC26A3 encodes a Cl-/HCO3- ion transporter that is also known as downregulated
      in adenoma (DRA) and is involved in HCO3-/mucus formation. The role of DRA in the
      epithelial barrier has not been previously established. In this study, we
      investigated the in vivo and in vitro mechanisms of DRA in the colon epithelial
      barrier. Immunofluorescence (IF) and co-immunoprecipitation (co-IP) studies
      reveal that DRA binds directly to tight junction (TJ) proteins and affects the
      expression of TJ proteins in polarized Caco-2BBe cells. Similarly, DRA
      colocalizes with ZO-1 in the intestinal epithelium. Knockdown or overexpression
      of DRA leads to alterations in TJ proteins and epithelial permeability. In
      addition, TNF-alpha treatment downregulates DRA by activating NF-kB and
      subsequently affecting intestinal epithelial barrier integrity. Furthermore,
      overexpression of DRA partly reverses the TNF-alpha-induced damage by stabilizing
      TJ proteins. Neutralization of TNF-alpha in dextran sulfate sodium (DSS)-induced
      colitis mice demonstrates improved the outcomes, and the therapeutic effect of
      the TNF-alpha neutralizing mAb is mediated in part by the preservation of DRA
      expression. These data suggest that DRA may be one of the therapeutic targets of
      TNF-alpha. Moreover, DRA delivered by adenovirus vector significantly prevents
      the exacerbation of colitis and improves epithelial barrier function by promoting
      the recovery of TJ proteins in DSS-treated mice. In conclusion, DRA plays a role
      in protecting the epithelial barrier and may be a therapeutic target in gut
      homeostasis.

PMID- 29330472
TI  - Amyloid deposition in a mouse model humanized at the transthyretin and retinol
      binding protein 4 loci.
AB  - Familial amyloidotic polyneuropathy is an autosomal dominant disorder caused by a
      point mutation in the transthyretin (TTR) gene. The process of TTR
      amyloidogenesis begins with rate-limiting dissociation of the TTR tetramer. Thus,
      the TTR stabilizers, such as Tafamidis and Diflunisal, are now in clinical
      trials. Mouse models will be useful to testing the efficacy of these drugs.
      Although several mouse models have been generated, they all express mouse Rbp4.
      Thus, human TTR associates with mouse RBP4, resulting in different kinetic and
      thermodynamic stability profiles of TTR tetramers. To overcome this problem, we
      previously produced humanized mouse strains at both the TTR and Rbp4 loci (Ttr
      hTTRVal30 , Ttr hTTRMet30 , and Rbp4 hRBP4 ). By mating these mice, we produced
      double-humanized mouse strains, Ttr hTTRVal30/hTTRVal30 :Rbp4 hRBP4/hRBP4 and Ttr
      hTTRVal30/Met30 :Rbp4 hRBP4/hRBP4 . We used conventional transgenic mouse strains
      on a wild-type (Ttr +/+ :Tg[6.0hTTRMet30]) or knockout Ttr background (Ttr-/
      :Tg[6.0hTTRMet30]) as reference strains. The double-humanized mouse showed 1/25
      of serum hTTR and 1/40 of serum hRBP4 levels. However, amyloid deposition was
      more pronounced in Ttr hTTRVal30/Met30 :Rbp4 hRBP4/hRBP4 than in conventional
      transgenic mouse strains. In addition, a similar amount of amyloid deposition was
      also observed in Ttr hTTRVal30/ hTTRVal30 :Rbp4 hRBP4/ hRBP4 mice that carried
      the wild-type human TTR gene. Furthermore, amyloid deposition was first observed
      in the sciatic nerve without any additional genetic change. In all strains, anti
      TTR antibody-positive deposits were found in earlier age and at higher percentage
      than amyloid fibril deposition. In double-humanized mice, gel filtration analysis
      of serum revealed that most hTTR was free of hRBP4, suggesting importance of free
      TTR for amyloid deposition.

PMID- 29330473
TI  - Endothelial heparan sulfate deficiency reduces inflammation and fibrosis in
      murine diabetic nephropathy.
AB  - Inflammation plays a vital role in the development of diabetic nephropathy, but
      the underlying regulatory mechanisms are only partially understood. Our previous
      studies demonstrated that, during acute inflammation, endothelial heparan sulfate
      (HS) contributes to the adhesion and transendothelial migration of leukocytes
      into perivascular tissues by direct interaction with L-selectin and the
      presentation of bound chemokines. In the current study, we aimed to assess the
      role of endothelial HS on chronic renal inflammation and fibrosis in a diabetic
      nephropathy mouse model. To reduce sulfation of HS specifically in the
      endothelium, we generated Ndst1 f/f Tie2Cre + mice in which N-deacetylase/N
      sulfotransferase-1 (Ndst1), the gene that initiates HS sulfation modifications in
      HS biosynthesis, was expressly ablated in endothelium. To induce diabetes, age
      matched male Ndst1 f/f Tie2Cre - (wild type) and Ndst1 f/f Tie2Cre + mice on a
      C57Bl/6J background were injected intraperitoneally with streptozotocin (STZ) (50
      mg/kg) on five consecutive days (N = 10-11/group). Urine and plasma were
      collected. Four weeks after diabetes induction the animals were sacrificed and
      kidneys were analyzed by immunohistochemistry and qRT-PCR. Compared to healthy
      controls, diabetic Ndst1 f/f Tie2Cre - mice showed increased glomerular
      macrophage infiltration, mannose binding lectin complement deposition and
      glomerulosclerosis, whereas these pathological reactions were prevented
      significantly in the diabetic Ndst1 f/f Tie2Cre + animals (all three p < 0.01).
      In addition, the expression of the podocyte damage marker desmin was
      significantly higher in the Ndst1 f/f Tie2Cre - group compared to the Ndst1 f/f
      Tie2Cre + animals (p < 0.001), although both groups had comparable numbers of
      podocytes. In the cortical tubulo-interstitium, similar analyses show decreased
      interstitial macrophage accumulation in the diabetic Ndst1 f/f Tie2Cre + animals
      compared to the diabetic Ndst1 f/f Tie2Cre - mice (p < 0.05). Diabetic Ndst1 f/f
      Tie2Cre + animals also showed reduced interstitial fibrosis as evidenced by
      reduced density of alphaSMA-positive myofibroblasts (p < 0.01), diminished
      collagen III deposition (p < 0.001) and reduced mRNA expression of collagen I (p
      < 0.001) and fibronectin (p < 0.001). Our studies indicate a pivotal role of
      endothelial HS in the development of renal inflammation and fibrosis in diabetic
      nephropathy in mice. These results suggest that HS is a possible target for
      therapy in diabetic nephropathy.

PMID- 29330475
TI  - Recent enhanced high-summer North Atlantic Jet variability emerges from three
      century context.
AB  - A recent increase in mid-latitude extreme weather events has been linked to
      Northern Hemisphere polar jet stream anomalies. To put recent trends in a
      historical perspective, long-term records of jet stream variability are needed.
      Here we combine two tree-ring records from the British Isles and the northeastern
      Mediterranean to reconstruct variability in the latitudinal position of the high
      summer North Atlantic Jet (NAJ) back to 1725 CE. We find that northward NAJ
      anomalies have resulted in heatwaves and droughts in northwestern Europe and
      southward anomalies have promoted wildfires in southeastern Europe. We further
      find an unprecedented increase in NAJ variance since the 1960s, which co-occurs
      with enhanced late twentieth century variance in the Central and North Pacific
      Basin. Our results suggest increased late twentieth century interannual
      meridional jet stream variability and support more sinuous jet stream patterns
      and quasi-resonant amplification as potential dynamic pathways for Arctic warming
      to influence mid-latitude weather.

PMID- 29330474
TI  - A De Novo FOXP1 Truncating Mutation in a Patient Originally Diagnosed as C
      Syndrome.
AB  - De novo FOXP1 mutations have been associated with intellectual disability (ID),
      motor delay, autistic features and a wide spectrum of speech difficulties. C
      syndrome (Opitz C trigonocephaly syndrome) is a rare and genetically
      heterogeneous condition, characterized by trigonocephaly, craniofacial anomalies
      and ID. Several different chromosome deletions and and point mutations in
      distinct genes have been associated with the disease in patients originally
      diagnosed as Opitz C. By whole exome sequencing we identified a de novo splicing
      mutation in FOXP1 in a patient, initially diagnosed as C syndrome, who suffers
      from syndromic intellectual disability with trigonocephaly. The mutation (c.1428
      + 1 G > A) promotes the skipping of exon 16, a frameshift and a premature STOP
      codon (p.Ala450GLyfs*13), as assessed by a minigene strategy. The patient
      reported here shares speech difficulties, intellectual disability and autistic
      features with other FOXP1 syndrome patients, and thus the diagnosis for this
      patient should be changed. Finally, since trigonocephaly has not been previously
      reported in FOXP1 syndrome, it remains to be proved whether it may be associated
      with the FOXP1 mutation.

PMID- 29330476
TI  - High-performance flexible supercapacitors based on electrochemically tailored
      three-dimensional reduced graphene oxide networks.
AB  - A simple approach for growing porous electrochemically reduced graphene oxide
      (pErGO) networks on copper wire, modified with galvanostatically deposited copper
      foam is demonstrated. The as-prepared pErGO networks on the copper wire are
      directly used to fabricate solid-state supercapacitor. The pErGO-based
      supercapacitor can deliver a specific capacitance (Csp) as high as 81+/-3 F g-1
      at 0.5 A g-1 with polyvinyl alcohol/H3PO4 gel electrolyte. The Csp per unit
      length and area are calculated as 40.5 mF cm-1 and 283.5 mF cm-2, respectively.
      The shape of the voltammogram retained up to high scan rate of 100 V s-1. The
      pErGO-based supercapacitor device exhibits noticeably high charge-discharge
      cycling stability, with 94.5% Csp retained even after 5000 cycles at 5 A g-1.
      Nominal change in the specific capacitance, as well as the shape of the
      voltammogram, is observed at different bending angles of the device even after
      5000 cycles. The highest energy density of 11.25 W h kg-1 and the highest power
      density of 5 kW kg-1 are also achieved with this device. The wire-based
      supercapacitor is scalable and highly flexible, which can be assembled
      with/without a flexible substrate in different geometries and bending angles for
      illustrating promising use in smart textile and wearable device.

PMID- 29330477
TI  - Labile organic carbon pools and enzyme activities of Pinus massoniana plantation
      soil as affected by understory vegetation removal and thinning.
AB  - The effects of forest management on carbon (C) sequestration are poorly
      understood, particularly in the Three Gorges Reservoir area. We aimed to identify
      the effects of forest management on C sequestration in Pinus massoniana
      plantations. An intact control forest (CK), a site undergoing regular shrub
      cutting with the simultaneous removal of residues (SC), a site under low
      intensity thinning (LIT), and a site under high-intensity thinning (HIT) were
      compared for soil labile organic carbon (LOC), related enzyme activities, and
      soil characteristics. Soil organic carbon (SOC) significantly decreased in the
      HIT treatment as compared with that in the CK treatment. Soil EOC, DOC, MBC
      contents in treated plots were higher than those in the CK treatment;
      particularly, the HIT treatment significantly increased those values in 0-10 cm
      layer. Thinning resulted in a decrease in cellulase and amylase activities, but
      an increase in invertase activity. In addition, the SOC content was significantly
      correlated with four enzymes activities and LOC components, which suggested that
      the soil LOC components and enzymes activities were sensitive to the changes of
      SOC. Our results suggest that high-intensity thinning treatment in Pinus
      massoniana plantation could significantly decrease the SOC content and lead to an
      increase of LOC components.

PMID- 29330479
TI  - Titania (TiO2) nanoparticles enhance the performance of growth-promoting
      rhizobacteria.
AB  - A novel use of nanotitania (TNs) as agents in the nanointerface interaction
      between plants and colonization of growth promoting rhizobacteria (PGPR) is
      presented. The effectiveness of PGPRs is related to the effectiveness of the
      technology used for their formulation. TNs produced by the Captigel patented
      SolGel approach, characterized by the transmission and scanning electron
      microscopy were used for formulation of the harsh environment PGPR strains.
      Changes in the biomass of wheat seedlings and in the density of single and double
      inoculants with and without TNs were monitored during two weeks of stress induced
      by drought salt and by the pathogen Fusarium culmorum. We show that double
      inoculants with TNs can attach stably to plant roots. Regression analysis
      indicates that there is a positive interaction between seedling biomass and TN
      treated second inoculant colonization. We conclude that TN treatment provides an
      effectual platform for PGPR rational application via design of root microbial
      community. Our studies illustrate the importance of considering natural soil
      nanoparticles for PGPR application and thereby may explain the generally observed
      inconsistent behavior of PGPRs in the field. These new advancements importantly
      contribute towards solving food security issues in changing climates. The model
      systems established here provide a basis for new PGPR nanomaterials research.

PMID- 29330478
TI  - Interaction of suppressor of cytokine signalling 3 with cavin-1 links SOCS3
      function and cavin-1 stability.
AB  - Effective suppression of JAK-STAT signalling by the inducible inhibitor
      "suppressor of cytokine signalling 3" (SOCS3) is essential for limiting
      signalling from cytokine receptors. Here we show that cavin-1, a component of
      caveolae, is a functionally significant SOCS3-interacting protein. Biochemical
      and confocal imaging demonstrate that SOCS3 localisation to the plasma membrane
      requires cavin-1. SOCS3 is also critical for cavin-1 stabilisation, such that
      deletion of SOCS3 reduces the expression of cavin-1 and caveolin-1 proteins,
      thereby reducing caveola abundance in endothelial cells. Moreover, the
      interaction of cavin-1 and SOCS3 is essential for SOCS3 function, as loss of
      cavin-1 enhances cytokine-stimulated STAT3 phosphorylation and abolishes SOCS3
      dependent inhibition of IL-6 signalling by cyclic AMP. Together, these findings
      reveal a new functionally important mechanism linking SOCS3-mediated inhibition
      of cytokine signalling to localisation at the plasma membrane via interaction
      with and stabilisation of cavin-1.

PMID- 29330480
TI  - Anti-correlated cortical networks arise from spontaneous neuronal dynamics at
      slow timescales.
AB  - In the highly interconnected architectures of the cerebral cortex, recurrent
      intracortical loops disproportionately outnumber thalamo-cortical inputs. These
      networks are also capable of generating neuronal activity without feedforward
      sensory drive. It is unknown, however, what spatiotemporal patterns may be solely
      attributed to intrinsic connections of the local cortical network. Using high
      density microelectrode arrays, here we show that in the isolated, primary
      somatosensory cortex of mice, neuronal firing fluctuates on timescales from
      milliseconds to tens of seconds. Slower firing fluctuations reveal two spatially
      distinct neuronal ensembles, which correspond to superficial and deeper layers.
      These ensembles are anti-correlated: when one fires more, the other fires less
      and vice versa. This interplay is clearest at timescales of several seconds and
      is therefore consistent with shifts between active sensing and anticipatory
      behavioral states in mice.

PMID- 29330482
TI  - Normal karyotype in myelofibrosis: is prognostic integrity affected by the number
      of metaphases analyzed?

PMID- 29330481
TI  - FDXR is a biomarker of radiation exposure in vivo.
AB  - Previous investigations in gene expression changes in blood after radiation
      exposure have highlighted its potential to provide biomarkers of exposure. Here,
      FDXR transcriptional changes in blood were investigated in humans undergoing a
      range of external radiation exposure procedures covering several orders of
      magnitude (cardiac fluoroscopy, diagnostic computed tomography (CT)) and
      treatments (total body and local radiotherapy). Moreover, a method was developed
      to assess the dose to the blood using physical exposure parameters. FDXR
      expression was significantly up-regulated 24 hr after radiotherapy in most
      patients and continuously during the fractionated treatment. Significance was
      reached even after diagnostic CT 2 hours post-exposure. We further showed that no
      significant differences in expression were found between ex vivo and in vivo
      samples from the same patients. Moreover, potential confounding factors such as
      gender, infection status and anti-oxidants only affect moderately FDXR
      transcription. Finally, we provided a first in vivo dose-response showing dose
      dependency even for very low doses or partial body exposure showing good
      correlation between physically and biologically assessed doses. In conclusion, we
      report the remarkable responsiveness of FDXR to ionising radiation at the
      transcriptional level which, when measured in the right time window, provides
      accurate in vivo dose estimates.

PMID- 29330483
TI  - Neural Correlates of Sexual Orientation in Heterosexual, Bisexual, and Homosexual
      Women.
AB  - We used fMRI to investigate neural correlates of responses to erotic pictures and
      videos in heterosexual (N = 26), bisexual (N = 26), and homosexual (N = 24)
      women, ages 25-50. We focused on the ventral striatum, an area of the brain
      associated with desire, extending previous findings from the sexual
      psychophysiology literature in which homosexual women had greater category
      specificity (relative to heterosexual and bisexual women) in their responses to
      male and female erotic stimuli. We found that homosexual women's subjective and
      neural responses reflected greater bias towards female stimuli, compared with
      bisexual and heterosexual women, whose responses did not significantly differ.
      These patterns were also suggested by whole brain analyses, with homosexual women
      showing category-specific activations of greater extents in visual and auditory
      processing areas. Bisexual women tended to show more mixed patterns, with
      activations more responsive to female stimuli in sensory processing areas, and
      activations more responsive to male stimuli in areas associated with social
      cognition.

PMID- 29330484
TI  - Single-cell RNA-sequencing resolves self-antigen expression during mTEC
      development.
AB  - The crucial capability of T cells for discrimination between self and non-self
      peptides is based on negative selection of developing thymocytes by medullary
      thymic epithelial cells (mTECs). The mTECs purge autoreactive T cells by
      expression of cell-type specific genes referred to as tissue-restricted antigens
      (TRAs). Although the autoimmune regulator (AIRE) protein is known to promote the
      expression of a subset of TRAs, its mechanism of action is still not fully
      understood. The expression of TRAs that are not under the control of AIRE also
      needs further characterization. Furthermore, expression patterns of TRA genes
      have been suggested to change over the course of mTEC development. Herein we have
      used single-cell RNA-sequencing to resolve patterns of TRA expression during mTEC
      development. Our data indicated that mTEC development consists of three distinct
      stages, correlating with previously described jTEC, mTEChi and mTEClo phenotypes.
      For each subpopulation, we have identified marker genes useful in future studies.
      Aire-induced TRAs were switched on during jTEC-mTEC transition and were expressed
      in genomic clusters, while otherwise the subsets expressed largely overlapping
      sets of TRAs. Moreover, population-level analysis of TRA expression frequencies
      suggested that such differences might not be necessary to achieve efficient
      thymocyte selection.

PMID- 29330485
TI  - The Structure of Metal Binding Domain 1 of the Copper Transporter ATP7B Reveals
      Mechanism of a Singular Wilson Disease Mutation.
AB  - Copper-transporter ATP7B maintains copper homeostasis in the human cells and
      delivers copper to the biosynthetic pathways for incorporation into the newly
      synthesized copper-containing proteins. ATP7B is a target of several hundred
      mutations that lead to Wilson disease, a chronic copper toxicosis. ATP7B contains
      a chain of six cytosolic metal-binding domains (MBDs), the first four of which
      (MBD1-4) are believed to be regulatory, and the last two (MBD5-6) are required
      for enzyme activity. We report the NMR structure of MBD1, the last unsolved metal
      binding domain of ATP7B. The structure reveals the disruptive mechanism of G85V
      mutation, one of the very few disease causing missense mutations in the MBD1-4
      region of ATP7B.

PMID- 29330486
TI  - New generation of drug delivery systems based on ginsenoside Rh2-, Lysine- and
      Arginine-treated highly porous graphene for improving anticancer activity.
AB  - In this study, Rh2-treated graphene oxide (GO-Rh2), lysine-treated highly porous
      graphene (Gr-Lys), arginine-treated Gr (Gr-Arg), Rh2-treated Gr-Lys (Gr-Lys-Rh2)
      and Rh2-treated Gr-Arg (Gr-Arg-Rh2) were synthesized. MTT assay was used for
      evaluation of cytotoxicity of samples on ovarian cancer (OVCAR3), breast cancer
      (MDA-MB), Human melanoma (A375) and human mesenchymal stem cells (MSCs) cell
      lines. The percentage of apoptotic cells was determined by terminal
      deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. The
      hemolysis and blood coagulation activity of nanostructures were performed.
      Interestingly, Gr-Arg, Gr-Lys, Gr-Arg-Rh2, and Gr-Lys-Rh2 were more active
      against cancer cell lines in comparison with their cytotoxic activity against
      normal cell lines (MSCs) with IC50 values higher than 100 MUg/ml. The results of
      TUNEL assay indicates a significant increase in the rates of TUNEL positive cells
      by increasing the concentrations of nanomaterials. Results were also shown that
      aggregation and changes of RBCs morphology were occurred in the presence of GO,
      GO-Rh2, Gr-Arg, Gr-Lys, Gr-Arg-Rh2, and Gr-Lys-Rh2. Note that all the samples had
      effect on blood coagulation system, especially on PTT. All nanostrucure act as
      antitumor drug so that binding of drugs to a nostructures is irresolvable and the
      whole structure enter to the cell as a drug.

PMID- 29330487
TI  - A Biomarker Characterizing Neurodevelopment with applications in Autism.
AB  - Despite great advances in neuroscience and genetic studies, our understanding of
      neurodevelopmental disorders is still quite limited. An important reason is not
      having objective psychiatric clinical tests. Here we propose a quantitative
      neurodevelopment assessment by studying natural movement outputs. Movement is
      central to behaviors: It involves complex coordination, temporal alterations, and
      precise dynamic controls. We carefully analyzed the continuous movement output
      data, collected with high definition electromagnetic sensors at millisecond time
      scales. We unraveled new metrics containing striking physiological information
      that was unseen neither by using traditional motion assessments nor by naked eye
      observations. Our putative biomarker leads to precise individualized
      classifications. It illustrates clear differences between Autism Spectrum
      Disorder (ASD) subjects from mature typical developing (TD) individuals. It
      provides an ASD complementary quantitative classification, which closely agrees
      with the clinicaly assessed functioning levels in the spectrum. It also
      illustrates TD potential age-related neurodevelopmental trajectories. Applying
      our movement biomarker to the parents of the ASD individuals studied in the
      cohort also shows a novel potential familial signature ASD tie. This paper
      proposes a putative behavioral biomarker to characterize the level of
      neurodevelopment with high predicting power, as illustrated in ASD subjects as an
      example.

PMID- 29330488
TI  - Motor skill learning and reward consumption differentially affect VTA activation.
AB  - Dopamine release from the ventral tegmental area (VTA) terminals in the primary
      motor cortex (M1) enables motor skill acquisition. Here, we test the hypothesis
      that dopaminergic VTA neurons projecting to M1 are activated when rewards are
      obtained during motor skill acquisition, but not during task execution at plateau
      performance, or by rewards obtained without performing skilled movements. Rats
      were trained to perform a skilled reaching task for 3 days (acquisition) or 7
      days (plateau). In combination with retrograde labelling of VTA-to-M1 projection
      neurons, double immunofluorescence for c-fos and tyrosine hydroxylase (TH) was
      used to assess activation of dopaminergic and non-dopaminergic VTA neurons.
      Dopaminergic VTA-to-M1 projection neurons were indeed activated during successful
      motor skill acquisition, but not when rats failed to learn or had reached plateau
      performance, nor by food rewards alone. By contrast, dopaminergic VTA neurons
      that did not project to M1 were activated by both skilled reaching and food
      rewards. Non-dopaminergic neurons were found to be activated by motor task
      performance at plateau, but not during skill acquisition. These results indicate
      that distinct populations of VTA neurons are activated by motor skill acquisition
      and task performance. Moreover, this activation is not merely related to
      consumption of food rewards.

PMID- 29330489
TI  - Decoding hind limb kinematics from neuronal activity of the dorsal horn neurons
      using multiple level learning algorithm.
AB  - Decoding continuous hind limb joint angles from sensory recordings of neural
      system provides a feedback for closed-loop control of hind limb movement using
      functional electrical stimulation. So far, many attempts have been done to
      extract sensory information from dorsal root ganglia and sensory nerves. In this
      work, we examine decoding joint angles trajectories from the single-electrode
      extracellular recording of dorsal horn gray matter of the spinal cord during
      passive limb movement in anesthetized cats. In this study, a processing framework
      based on ensemble learning approach is propose to combine firing rate (FR) and
      interspike interval (ISI) information of the neuronal activity. For this purpose,
      a stacked generalization approach based on recurrent neural network is proposed
      to enhance decoding accuracy of the movement kinematics. The results show that
      the high precision neural decoding of limb movement can be achieved even with a
      single electrode implanted in the spinal cord gray matter.

PMID- 29330491
TI  - Application of Hydrazine-Embedded Heterocyclic Compounds to High Voltage
      Rechargeable Lithium Organic Batteries.
AB  - Hydrazine-embedded heterocyclic compounds with dimeric dimethylacridine (1b),
      carbazole (2b), and phenothiazine (3b) skeletons were applied to cathode active
      materials of rechargeable lithium organic batteries, and the performance of the
      batteries was evaluated. The charge/discharge curves exhibited clear plateaus in
      the high voltage range of 3.3-3.7 V. The capacities of the plateau regions were
      comparable to the calculated capacities corresponding to the one-electron redox
      of the molecules. The amount of the active compound 3b could be increased up to
      30 wt% in the electrode composite, and fast charge/discharge performance was also
      observed.

PMID- 29330490
TI  - Differentially expressed microRNAs between cattleyak and yak testis.
AB  - Cattleyak are interspecific hybrids between cattle and yak, exhibiting the same
      prominent adaptability as yak and much higher performances than yak. However,
      male infertility of cattleyak resulted from spermatogenic arrest has greatly
      restricted their effective utilization in yak breeding. In past decades, much
      work has been done to investigate the mechanisms of spermatogenic arrest, but
      little is known about the differences of the post-transcriptional regulators
      between cattleyak and yak, which may contribute to the impaired spermatogenesis.
      MiRNAs, a class of endogenous non-coding small RNA, were revealed to play crucial
      roles in regulating gene expression at post-transcriptional level. In the present
      study, we identified 50 differentially expressed (DE) known miRNAs and 11 novel
      miRNAs by using Illumina HISeq and bioinformatic analysis. A total of 50 putative
      target sites for the 13 DE known miRNAs and 30 for the 6 DE novel miRNAs were
      identified, respectively. GO and KEGG analyses were performed to reveal the
      functions of target genes for DE miRNAs. In addition, RT-qPCR was performed to
      validate the expression of the DE miRNAs and its targets. The identification of
      these miRNAs may provide valuable information for a better understanding of
      spermatogenic arrest in cattleyak.

PMID- 29330492
TI  - Turning a normal microscope into a super-resolution instrument using a scanning
      microlens array.
AB  - We report dielectric microsphere array-based optical super-resolution microscopy.
      A dielectric microsphere that is placed on a sample is known to generate a
      virtual image with resolution better than the optical diffraction limit. However,
      a limitation of such type of super-resolution microscopy is the restricted field
      of-view, essentially limited to the central area of the microsphere-generated
      image. We overcame this limitation by scanning a micro-fabricated array of
      ordered microspheres over the sample using a customized algorithm that moved step
      by-step a motorized stage, meanwhile the microscope-mounted camera was taking
      pictures at every step. Finally, we stitched together the extracted central parts
      of the virtual images that showed super-resolution into a mosaic image. We
      demonstrated 130 nm lateral resolution (~lambda/4) and 5 * 105 um2 scanned
      surface area using a two by one array of barium titanate glass microspheres in
      oil-immersion environment. Our findings may serve as a basis for widespread
      applications of affordable optical super-resolution microscopy.

PMID- 29330493
TI  - Development of versatile non-homologous end joining-based knock-in module for
      genome editing.
AB  - CRISPR/Cas9-based genome editing has dramatically accelerated genome engineering.
      An important aspect of genome engineering is efficient knock-in technology. For
      improved knock-in efficiency, the non-homologous end joining (NHEJ) repair
      pathway has been used over the homology-dependent repair pathway, but there
      remains a need to reduce the complexity of the preparation of donor vectors. We
      developed the versatile NHEJ-based knock-in module for genome editing (VIKING).
      Using the consensus sequence of the time-honored pUC vector to cut donor vectors,
      any vector with a pUC backbone could be used as the donor vector without
      customization. Conditions required to minimize random integration rates of the
      donor vector were also investigated. We attempted to isolate null lines of the
      VDR gene in human HaCaT keratinocytes using knock-in/knock-out with a selection
      marker cassette, and found 75% of clones isolated were successfully knocked-in.
      Although HaCaT cells have hypotetraploid genome composition, the results suggest
      multiple clones have VDR null phenotypes. VIKING modules enabled highly efficient
      knock-in of any vectors harboring pUC vectors. Users now can insert various
      existing vectors into an arbitrary locus in the genome. VIKING will contribute to
      low-cost genome engineering.

PMID- 29330495
TI  - Large unexplained suite of chemically reactive compounds present in ambient air
      due to biomass fires.
AB  - Biomass fires impact global atmospheric chemistry. The reactive compounds emitted
      and formed due to biomass fires drive ozone and organic aerosol formation,
      affecting both air quality and climate. Direct hydroxyl (OH) Reactivity
      measurements quantify total gaseous reactive pollutant loadings and comparison
      with measured compounds yields the fraction of unmeasured compounds. Here, we
      quantified the magnitude and composition of total OH reactivity in the north-west
      Indo-Gangetic Plain. More than 120% increase occurred in total OH reactivity (28
      s-1 to 64 s-1) and from no missing OH reactivity in the normal summertime air,
      the missing OH reactivity fraction increased to ~40 % in the post-harvest
      summertime period influenced by large scale biomass fires highlighting presence
      of unmeasured compounds. Increased missing OH reactivity between the two
      summertime periods was associated with increased concentrations of compounds with
      strong photochemical source such as acetaldehyde, acetone, hydroxyacetone,
      nitromethane, amides, isocyanic acid and primary emissions of acetonitrile and
      aromatic compounds. Currently even the most detailed state-of-the art atmospheric
      chemistry models exclude formamide, acetamide, nitromethane and isocyanic acid
      and their highly reactive precursor alkylamines (e.g. methylamine, ethylamine,
      dimethylamine, trimethylamine). For improved understanding of atmospheric
      chemistry-air quality-climate feedbacks in biomass-fire impacted atmospheric
      environments, future studies should include these compounds.

PMID- 29330494
TI  - Characterizing the bacterial microbiota in different gastrointestinal tract
      segments of the Bactrian camel.
AB  - The bacterial community plays important roles in the gastrointestinal tracts
      (GITs) of animals. However, our understanding of the microbial communities in the
      GIT of Bactrian camels remains limited. Here, we describe the bacterial
      communities from eight different GIT segments (rumen, reticulum, abomasum,
      duodenum, ileum, jejunum, caecum, colon) and faeces determined from 11 Bactrian
      camels using 16S rRNA gene amplicon sequencing. Twenty-seven bacterial phyla were
      found in the GIT, with Firmicutes, Verrucomicrobia and Bacteroidetes
      predominating. However, there were significant differences in microbial community
      composition between segments of the GIT. In particular, a greater proportion of
      Akkermansia and Unclassified Ruminococcaceae were found in the large intestine
      and faecal samples, while more Unclassified Clostridiales and Unclassified
      Bacteroidales were present in the in forestomach and small intestine. Comparative
      analysis of the microbiota from different GIT segments revealed that the
      microbial profile in the large intestine was like that in faeces. We also
      predicted the metagenomic profiles for the different GIT regions. In forestomach,
      there was enrichment associated with replication and repair and amino acid
      metabolism, while carbohydrate metabolism was enriched in the large intestine and
      faeces. These results provide profound insights into the GIT microbiota of
      Bactrian camels.

PMID- 29330496
TI  - Framing Continental Shelf Waves in the southern Adriatic Sea, a further flushing
      factor beyond dense water cascading.
AB  - Continental Shelf Waves (CSWs) are oscillatory phenomena migrating along the
      continental margins, controlled by the interplay of rotation and bathymetric
      gradients. Here we combine observational data from five moored current meters and
      high-resolution hydrodynamic model fields for describing the generation and
      propagation of CSWs along the Southern Adriatic Margin (SAM, eastern
      Mediterranean Sea), where the possibility of their occurrence has been
      theoretically hypothesised but not experimentally observed up to now. Results
      show that in spring 2012 a train of CSWs with 35-87 km wavelength and 2-4 day
      period was generated on the northern sectors of the SAM and propagated southwards
      along its western slope. Along their path, CSWs modify their apparent frequency
      and oscillation mode as an effect of the background current and scattering caused
      by changes in the continental margin morphology. This signal appears as a
      persistent feature triggered by the inflow of a dense water vein formed in the
      northern Adriatic Sea, propagating upwelling and downwelling patterns along broad
      sectors of the continental slope. CSWs thus appear as an additional remote
      controlled mechanism for cross-shelf exchange of water, sediment and nutrients in
      the SAM, besides the well-acknowledged dense water downflow along preferential
      pathways driven by local topographic constraints.

PMID- 29330498
TI  - Replication of biocompatible, nanotopographic surfaces.
AB  - The ability of cells to sense and respond to nanotopography is being implicated
      as a key element in many physiological processes such as cell differentiation,
      immune response, and wound healing, as well as in pathologies such as cancer
      metastasis. To understand how nanotopography affects cellular behaviors, new
      techniques are required for the mass production of biocompatible, rigid
      nanotopographic surfaces. Here we introduce a method for the rapid and
      reproducible production of biocompatible, rigid, acrylic nanotopographic
      surfaces, and for the functionalization of the surfaces with adhesion-promoting
      molecules for cell experiments. The replica surfaces exhibit high optical
      transparency, which is advantageous for high-resolution, live-cell imaging. As a
      representative application, we demonstrate that epithelial cells form focal
      adhesions on surfaces composed of nanoscale ridges and grooves, and that the
      focal adhesions prefer to localize on the nanoridges. We further demonstrate that
      both F-actin and microtubules align along the nanoridges, but only F-actin aligns
      along the nanogrooves. The mass production of nanotopographic surfaces opens the
      door to the investigation of the effect of physical cues on the spatial
      distribution and the dynamics of intracellular proteins, and to the study of the
      mechanism of mechanosensing in processes such as cell migration, phagocytosis,
      division, and differentiation.

PMID- 29330497
TI  - Visual learning with reduced adaptation is eccentricity-specific.
AB  - Visual learning is known to be specific to the trained target location, showing
      little transfer to untrained locations. Recently, learning was shown to transfer
      across equal-eccentricity retinal-locations when sensory adaptation due to
      repetitive stimulation was minimized. It was suggested that learning transfers to
      previously untrained locations when the learned representation is location
      invariant, with sensory adaptation introducing location-dependent
      representations, thus preventing transfer. Spatial invariance may also fail when
      the trained and tested locations are at different distance from the center of
      gaze (different retinal eccentricities), due to differences in the corresponding
      low-level cortical representations (e.g. allocated cortical area decreases with
      eccentricity). Thus, if learning improves performance by better classifying
      target-dependent early visual representations, generalization is predicted to
      fail when locations of different retinal eccentricities are trained and tested in
      the absence sensory adaptation. Here, using the texture discrimination task, we
      show specificity of learning across different retinal eccentricities (4-8 degrees
      ) using reduced adaptation training. The existence of generalization across equal
      eccentricity locations but not across different eccentricities demonstrates that
      learning accesses visual representations preceding location independent
      representations, with specificity of learning explained by inhomogeneous sensory
      representation.

PMID- 29330499
TI  - Three-Dimensional Physical Model-Assisted Planning and Navigation for
      Laparoscopic Partial Nephrectomy in Patients with Endophytic Renal Tumors.
AB  - Resection of completely endophytic renal tumors is a huge challenge for surgeons
      due to a lack of definite visual clues, especially in the laparoscopic approach.
      Three-dimensional (3D) kidney models, which can illustrate the clear relationship
      between renal masses and surrounding health tissues, were considered as reliable
      tools for understanding renal tumor characteristics in previous studies. We
      hypothesized that 3D kidney models can be used not only for planning but also for
      navigating laparoscopic partial nephrectomy (LPN) in patients with completely
      endophytic renal tumors. In this study, we successfully constructed five cases of
      3D kidney models for assisted planning and navigation for LPN in endophytic renal
      tumors. The renal masses and surrounding normal parenchyma of the patient
      specific 3D models were dyed by different colorants for clear illustration. All
      patients experienced acceptable perioperative outcomes, and no patient suffered
      serious relative complications. The 3D kidney models were considered as a
      reliable tool based on clinical outcome and postoperative questionnaire results.
      This study is the first report of 3D kidney models for patients with completely
      endophytic tumors. 3D kidney models can aid surgeons in understanding the
      characteristics of renal tumors and potentially support assisted planning and
      performance of LPN in endophytic tumor cases.

PMID- 29330501
TI  - Novel endogenous simian retroviral integrations in Vero cells: implications for
      quality control of a human vaccine cell substrate.
AB  - African green monkey (AGM)-derived Vero cells have been utilized to produce
      various human vaccines. The Vero cell genome harbors a variety of simian
      endogenous type D retrovirus (SERV) sequences. In this study, a transcriptome
      analysis showed that DNA hypomethylation released the epigenetic repression of
      SERVs in Vero cells. Moreover, comparative genomic analysis of three Vero cell
      sublines and an AGM reference revealed that the genomes of the sublines have ~80
      SERV integrations. Among them, ~60 integrations are present within all three cell
      sublines and absent from the reference sequence. At least several of these
      integrations consist of complete SERV proviruses. These results strongly suggest
      that SERVs integrated in the genome of Vero cells did not retrotranspose after
      the establishment of the cell lineage as far as cells were maintained under
      standard culture and passage conditions, providing a scientific basis for
      controlling the quality of pharmaceutical cell substrates and their derived
      biologics.

PMID- 29330500
TI  - Integration of GWAS, pathway and network analyses reveals novel mechanistic
      insights into the synthesis of milk proteins in dairy cows.
AB  - The quantities and proportions of protein fractions have notable effects on the
      nutritional and technological value of milk. Although much is known about the
      effects of genetic variants on milk proteins, the complex relationships among the
      set of genes and pathways regulating the different protein fractions synthesis
      and secretion into milk in dairy cows are still not completely understood. We
      conducted genome-wide association studies (GWAS) for milk nitrogen fractions in a
      cohort of 1,011 Brown Swiss cows, which uncovered 170 significant single
      nucleotide polymorphism (SNPs), mostly located on BTA6 and BTA11. Gene-set
      analysis and the network-based Associated Weight Matrix approach revealed that
      the milk proteins associated genes were involved in several biological functions,
      particularly ion and cation transmembrane transporter activity and neuronal and
      hormone signalling, according to the structure and function of casein micelles.
      Deeper analysis of the transcription factors and their predicted target genes
      within the network revealed that GFI1B, ZNF407 and NR5A1 might act as master
      regulators of milk protein synthesis and secretion. The information acquired
      provides novel insight into the regulatory mechanisms controlling milk protein
      synthesis and secretion in bovine mammary gland and may be useful in breeding
      programmes aimed at improving milk nutritional and/or technological properties.

PMID- 29330503
TI  - Effects of larvae density and food concentration on Crown-of-Thorns seastar
      (Acanthaster cf. solaris) development in an automated flow-through system.
AB  - Coral-eating Crown-of-Thorns Sea stars (Acanthaster spp.) are major contributors
      to coral reef loss in the Indo-Pacific region. A release from food limitation of
      their planktotrophic larvae through enhanced pelagic productivity is one of the
      main hypothesis explaining population outbreaks ('nutrient limitation
      hypothesis'). To improve the understanding of these outbreaks we developed an
      automated flow- through larvae rearing system that maintained food (microalgae)
      at set levels over the course of four 15d experiments. This resulted in stable
      food concentrations in experimental tanks. Increased algae concentrations had a
      significant positive effect on larval development and size at 10 and 15 days post
      fertilization (dpf). Larvae densities had no effect at 10 dpf. At 15 dpf greater
      larvae densities were associated with declines in larvae size. Larval development
      was slowed under higher larvae densities. Thus, the effects of algae
      concentration and larvae density were additive at 15 dpf, with larvae under low
      densities at a given algae concentration being further developed than those under
      higher densities. The development of a flow-through system gives greater insight
      into the effect of algae and larvae concentrations on Acanthaster development,
      and the system can be applied to further test the nutrient-limitation hypothesis
      for present and future outbreaks.

PMID- 29330502
TI  - Targeting Insulin-Like Growth Factor-I and Extracellular Matrix Interactions in
      Melanoma Progression.
AB  - Insulin-like growth factor (IGF)-I binds to the ECM protein vitronectin (VN)
      through IGF binding proteins (IGFBPs) to enhance proliferation and migration of
      skin keratinocytes and fibroblasts. Although evidence exists for the role of
      individual components of the complex (IGF-I, IGFBP-3 and VN), the cellular
      functions stimulated by these proteins together as a complex remains un
      investigated in melanoma cells. We report here that the IGF-I:IGFBP-3:VN trimeric
      complex stimulates a dose-dependent increase in the proliferation and migration
      of WM35 and Sk-MEL28 melanoma cells. In 3D MatrigelTM and hydrogel cultures, both
      cell lines formed primary tumor-like spheroids, which increased in size in a dose
      dependent manner in response to the trimeric complex. Furthermore, we reveal
      IGFBP-3:VN protein complexes in malignant melanoma and squamous cell carcinoma
      patient tissues, where the IGFBP-3:VN complex was seen to be predominantly tumor
      cell-associated. Peptide antagonists designed to target the binding of IGF
      I:IGFBP-3 to VN were demonstrated to inhibit IGF-I:IGFBP-3:VN-stimulated cell
      migration, invasion and 3D tumor cell growth of melanoma cells. Overall, this
      study provides new data on IGF:ECM interactions in skin malignancies and
      demonstrates the potential usefulness of a growth factor:ECM-disrupting strategy
      for abrogating tumor progression.

PMID- 29330504
TI  - Unique Roles of beta-Arrestin in GPCR Trafficking Revealed by Photoinducible
      Dimerizers.
AB  - Intracellular trafficking of G protein-coupled receptors (GPCRs) controls their
      localization and degradation, which affects a cell's ability to adapt to
      extracellular stimuli. Although the perturbation of trafficking induces important
      diseases, these trafficking mechanisms are poorly understood. Herein, we
      demonstrate an optogenetic method using an optical dimerizer, cryptochrome (CRY)
      and its partner protein (CIB), to analyze the trafficking mechanisms of GPCRs and
      their regulatory proteins. Temporally controlling the interaction between beta
      arrestin and beta2-adrenergic receptor (ADRB2) reveals that the duration of the
      beta-arrestin-ADRB2 interaction determines the trafficking pathway of ADRB2.
      Remarkably, the phosphorylation of ADRB2 by G protein-coupled receptor kinases is
      unnecessary to trigger clathrin-mediated endocytosis, and beta-arrestin
      interacting with unphosphorylated ADRB2 fails to activate mitogen-activated
      protein kinase (MAPK) signaling, in contrast to the ADRB2 agonist isoproterenol.
      Temporal control of beta-arrestin-GPCR interactions will enable the investigation
      of the unique roles of beta-arrestin and the mechanism by which it regulates beta
      arrestin-specific trafficking pathways of different GPCRs.

PMID- 29330505
TI  - Over-expression of a retinol dehydrogenase (SRP35/DHRS7C) in skeletal muscle
      activates mTORC2, enhances glucose metabolism and muscle performance.
AB  - SRP-35 is a short-chain dehydrogenase/reductase belonging to the DHRS7C
      dehydrogenase/ reductase family 7. Here we show that its over-expression in mouse
      skeletal muscles induces enhanced muscle performance in vivo, which is not
      related to alterations in excitation-contraction coupling but rather linked to
      enhanced glucose metabolism. Over-expression of SRP-35 causes increased
      phosphorylation of AktS473, triggering plasmalemmal targeting of GLUT4 and higher
      glucose uptake into muscles. SRP-35 signaling involves RARalpha and RARgamma (non
      genomic effect), PI3K and mTORC2. We also demonstrate that all-trans retinoic
      acid, a downstream product of the enzymatic activity of SRP-35, mimics the effect
      of SRP-35 in skeletal muscle, inducing a synergistic effect with insulin on
      AKTS473 phosphorylation. These results indicate that SRP-35 affects skeletal
      muscle metabolism and may represent an important target for the treatment of
      metabolic diseases.

PMID- 29330506
TI  - Impact of wave whitecapping on land falling tropical cyclones.
AB  - Predicting tropical cyclone structure and evolution remains challenging.
      Particularly, the surface wave interactions with the continental shelf and their
      impact on tropical cyclones have received very little attention. Through a series
      of state-of-the-art high-resolution, fully-coupled ocean-wave and atmosphere
      ocean-wave experiments, we show here, for the first time, that in presence of
      continental shelf waves can cause substantial cooling of the sea surface. Through
      whitecapping there is a transfer of momentum from the surface which drives deeper
      vertical mixing. It is the waves and not just the wind which become the major
      driver of stratified coastal ocean ahead-of-cyclone cooling. In the fully-coupled
      atmosphere-ocean-wave model a negative feedback is found. The maximum wind speed
      is weaker and the damaging footprint area of hurricane-force winds is reduced by
      up to 50% due to the strong wave induced ocean cooling ahead. Including wave
      ocean coupling is important to improve land falling tropical cyclone intensity
      predictions for the highly populated and vulnerable coasts.

PMID- 29330508
TI  - Picometer polar atomic displacements in strontium titanate determined by resonant
      X-ray diffraction.
AB  - Physical properties of crystalline materials often manifest themselves as atomic
      displacements either away from symmetry positions or driven by external fields.
      Especially the origin of multiferroic or magnetoelectric effects may be hard to
      ascertain as the related displacements can reach the detection limit. Here we
      present a resonant X-ray crystal structure analysis technique that shows enhanced
      sensitivity to minute atomic displacements. It is applied to a recently found
      crystalline modification of strontium titanate that forms in single crystals
      under electric field due to oxygen vacancy migration. The phase has demonstrated
      unexpected properties, including piezoelectricity and pyroelectricity, which can
      only exist in non-centrosymmetric crystals. Apart from that, the atomic structure
      has remained elusive and could not be obtained by standard methods. Using
      resonant X-ray diffraction, we determine atomic displacements with sub-picometer
      precision and show that the modified structure of strontium titanate corresponds
      to that of well-known ferroelectrics such as lead titanate.

PMID- 29330507
TI  - Uncovering the anticancer mechanism of Compound Kushen Injection against HCC by
      integrating quantitative analysis, network analysis and experimental validation.
AB  - Compound Kushen Injection (CKI) is a Traditional Chinese Medicine (TCM)
      preparation that has been clinically used in China to treat various types of
      solid tumours. Although several studies have revealed that CKI can inhibit the
      proliferation of hepatocellular carcinoma (HCC) cell lines, the active compounds,
      potential targets and pathways involved in these effects have not been
      systematically investigated. Here, we proposed a novel idea of "main active
      compound-based network pharmacology" to explore the anti-cancer mechanism of CKI.
      Our results showed that CKI significantly suppressed the proliferation and
      migration of SMMC-7721 cells. Four main active compounds of CKI (matrine,
      oxymatrine, sophoridine and N-methylcytisine) were confirmed by the integration
      of ultra-performance liquid chromatography/mass spectrometry (UPLC-MS) with cell
      proliferation assays. The potential targets and pathways involved in the anti-HCC
      effects of CKI were predicted by a network pharmacology approach, and some of the
      crucial proteins and pathways were further validated by western blotting and
      metabolomics approaches. Our results indicated that CKI exerted anti-HCC effects
      via the key targets MMP2, MYC, CASP3, and REG1A and the key pathways of
      glycometabolism and amino acid metabolism. These results provide insights into
      the mechanism of CKI by combining quantitative analysis of components, network
      pharmacology and experimental validation.

PMID- 29330509
TI  - Transcriptome analysis reveals carbohydrate-mediated liver immune responses in
      Epinephelus akaara.
AB  - As the cheapest energy source, carbohydrates are used in fish feeds to improve
      physical quality and reduce catabolism of proteins and lipids. The liver is the
      primary organ for metabolism and is also an important site of immune regulation.
      Here, we investigated the effect of different dietary carbohydrate levels on
      growth and health by evaluating the liver transcriptome of Epinephelus akaara. In
      this study, E. akaara juveniles were fed diets containing few (0% corn starch),
      moderate (18% corn starch), and high (30% corn starch) levels of dietary
      carbohydrate. After an 8-week feeding trial, E. akaara fed 30% dietary
      carbohydrates exhibited poor growth performance compared with those fed 0% and
      18% dietary carbohydrates (P > 0.05). Genes related to the immune system,
      including IL8, TLR9, CXCR4, CCL4, and NFkappaB inhibitor alpha, were over
      expressed in E. akaara fed the highest level of carbohydrate (30%). This general
      over-expression could indicate activation of inflammatory processes in the liver.
      The liver transcriptome data of E. akaara reported here indicate that high
      carbohydrate level of diet can lead to poor growth and inflammatory immune
      response in E. akaara.

PMID- 29330510
TI  - Shaping and Controlled Fragmentation of Liquid Metal Droplets through Cavitation.
AB  - Targeting micrometer sized metal droplets with near-infrared sub-picosecond laser
      pulses generates intense stress-confined acoustic waves within the droplet.
      Spherical focusing amplifies their pressures. The rarefaction wave nucleates
      cavitation at the center of the droplet, which explosively expands with a
      repeatable fragmentation scenario resulting into high-speed jetting. We predict
      the number of jets as a function of the laser energy by coupling the cavitation
      bubble dynamics with Rayleigh-Taylor instabilities. This provides a path to
      control cavitation and droplet shaping of liquid metals in particular for their
      use as targets in extreme-UV light sources.

PMID- 29330511
TI  - Testing density-functional approximations on a lattice and the applicability of
      the related Hohenberg-Kohn-like theorem.
AB  - We present a metric-space approach to quantify the performance of approximations
      in lattice density-functional theory for interacting many-body systems and to
      explore the regimes where the Hohenberg-Kohn-type theorem on fermionic lattices
      is applicable. This theorem demonstrates the existence of one-to-one mappings
      between particle densities, wave functions and external potentials. We then focus
      on these quantities, and quantify how far apart in metric space the approximated
      and exact ones are. We apply our method to the one-dimensional Hubbard model for
      different types of external potentials, and assess the regimes where it is
      applicable to one of the most used approximations in density-functional theory,
      the local density approximation (LDA). We find that the potential distance may
      have a very different behaviour from the density and wave function distances, in
      some cases even providing the wrong assessments of the LDA performance trends. We
      attribute this to the systems reaching behaviours which are borderline for the
      applicability of the one-to-one correspondence between density and external
      potential. On the contrary the wave function and density distances behave
      similarly and are always sensitive to system variations. Our metric-based method
      correctly predicts the regimes where the LDA performs fairly well and the regimes
      where it fails. This suggests that our method could be a practical tool for
      testing the efficiency of density-functional approximations.

PMID- 29330512
TI  - Inactivated rotavirus vaccine by parenteral administration induces mucosal
      immunity in mice.
AB  - To improve the safety and efficacy of oral rotavirus vaccines, we developed an
      inactivated rotavirus vaccine (IRV) for parenteral administration. Since it
      remains unknown whether parenteral vaccination can induce mucosal immunity, we
      performed a comprehensive assessment of immune responses to IRV in mice with an
      adjuvant-free dissolving polymer MN patch or by alum-adjuvanted IM injection. We
      demonstrated that IRV induced the expression of the gut homing receptor LPAM-1 on
      T and B cells in spleen and mLN of vaccinated mice. MN patch IRV vaccination
      induced a slight Th1 phenotype while IM vaccination induced a balanced Th1/Th2
      phenotype. In addition, a dose-sparing effect was seen for rotavirus-specific
      serum IgG and neutralizing activity for both vaccination routes. Our study is the
      first to show that parenterally administered IRV can induce mucosal immunity in
      the gut, in addition to strong serum antibody response, and is a promising
      candidate vaccine in achieving global immunization against rotavirus.

PMID- 29330513
TI  - Magnetic and structural properties of glass-coated Heusler-type microwires
      exhibiting martensitic transformation.
AB  - We have studied magnetic and structural properties of the Heusler-type Ni-Mn-Ga
      glass-coated microwires prepared by Tailor-Ulitovsky technique. As-prepared
      sample presents magnetoresistance effect and considerable dependence of
      magnetization curves (particularly magnetization values) on magnetic field
      attributed to the magnetic and atomic disorder. Annealing strongly affects the
      temperature dependence of magnetization and Curie temperature of microwires.
      After annealing of the microwires at 973 K, the Curie temperature was enhanced to
      about 280 K which is beneficial for the magnetic solid state refrigeration. The
      observed hysteretic anomalies on the temperature dependences of resistance and
      magnetization in the as-prepared and annealed samples are produced by the
      martensitic transformation. The magnetoresistance and magnetocaloric effects have
      been investigated to illustrate a potential technological capability of studied
      microwires.

PMID- 29330514
TI  - A comparison of static and dynamic cerebral autoregulation during mild whole-body
      cold stress in individuals with and without cervical spinal cord injury: a pilot
      study.
AB  - STUDY DESIGN: Experimental study. OBJECTIVES: To characterize static and dynamic
      cerebral autoregulation (CA) of individuals with cervical spinal cord injury
      (SCI) compared to able-bodied controls in response to moderate increases in mean
      arterial pressure (MAP) caused by mild whole-body cold stress. SETTING: Japan
      METHODS: Five men with complete autonomic cervical SCI (sustained > 5 y) and six
      age-matched able-bodied men participated in hemodynamic, temperature,
      catecholamine and respiratory measurements for 60 min during three consecutive
      stages: baseline (10 min; 33  degrees C water through a thin-tubed whole-body
      suit), mild cold stress (20 min; 25  degrees C water), and post-cold recovery (30
      min; 33  degrees C water). Static CA was determined as the ratio between mean
      changes in middle cerebral artery blood velocity and MAP, dynamic CA as transfer
      function coherence, gain, and phase between spontaneous changes in MAP to middle
      cerebral artery blood velocity. RESULTS: MAP increased in both groups during cold
      and post-cold recovery (mean differences: 5-10 mm Hg; main effect of time: p =
      0.001). Static CA was not different between the able-bodied vs. the cervical SCI
      group (mean (95% confidence interval (CI)) of between-group difference: -4 (-11
      to 3) and -2 (-5 to 1) cm/s/mm Hg for cold (p = 0.22) and post-cold (p = 0.24),
      respectively). At baseline, transfer function phase was shorter in the cervical
      SCI group (mean (95% CI) of between-group difference: 0.6 (0.2 to 1.0) rad; p =
      0.006), while between-group differences in changes in phase were not different in
      response to the cold stress (interaction term: p = 0.06). CONCLUSIONS: This pilot
      study suggests that static CA is similar between individuals with cervical SCI
      and able-bodied controls in response to moderate increases in MAP, while dynamic
      CA may be impaired in cervical SCI because of disturbed sympathetic control.

PMID- 29330515
TI  - HyphaTracker: An ImageJ toolbox for time-resolved analysis of spore germination
      in filamentous fungi.
AB  - The dynamics of early fungal development and its interference with physiological
      signals and environmental factors is yet poorly understood. Especially
      computational analysis tools for the evaluation of the process of early spore
      germination and germ tube formation are still lacking. For the time-resolved
      analysis of conidia germination of the filamentous ascomycete Fusarium fujikuroi
      we developed a straightforward toolbox implemented in ImageJ. It allows for
      processing of microscopic acquisitions (movies) of conidial germination starting
      with drift correction and data reduction prior to germling analysis. From the
      image time series germling related region of interests (ROIs) are extracted,
      which are analysed for their area, circularity, and timing. ROIs originating from
      germlings crossing other hyphae or the image boundaries are omitted during
      analysis. Each conidium/hypha is identified and related to its origin, thus
      allowing subsequent categorization. The efficiency of HyphaTracker was proofed
      and the accuracy was tested on simulated germlings at different signal-to-noise
      ratios. Bright-field microscopic images of conidial germination of rhodopsin
      deficient F. fujikuroi mutants and their respective control strains were analysed
      with HyphaTracker. Consistent with our observation in earlier studies the CarO
      deficient mutant germinated earlier and grew faster than other, CarO expressing
      strains.

PMID- 29330516
TI  - Drinking by amphibious fish: convergent evolution of thirst mechanisms during
      vertebrate terrestrialization.
AB  - Thirst aroused in the forebrain by angiotensin II (AngII) or buccal drying
      motivates terrestrial vertebrates to search for water, whereas aquatic fish can
      drink surrounding water only by reflex swallowing generated in the hindbrain.
      Indeed, AngII induces drinking through the hindbrain even after removal of the
      whole forebrain in aquatic fish. Here we show that AngII induces thirst also in
      the amphibious mudskipper goby without direct action on the forebrain, but
      through buccal drying. Intracerebroventricular injection of AngII motivated
      mudskippers to move into water and drink as with tetrapods. However, AngII
      primarily increased immunoreactive c-Fos at the hindbrain swallowing center where
      AngII receptors were expressed, as in other ray-finned fish, and such direct
      action on the forebrain was not found. Behavioural analyses showed that loss of
      buccal water on land by AngII-induced swallowing, by piercing holes in the
      opercula, or by water-absorptive gel placed in the cavity motivated mudskippers
      to move to water for refilling. Since sensory detection of water at the bucco
      pharyngeal cavity like 'dry mouth' has recently been noted to regulate thirst in
      mammals, similar mechanisms seem to have evolved in distantly related species in
      order to solve osmoregulatory problems during terrestrialization.

PMID- 29330517
TI  - Iron-induced calcification in human aortic vascular smooth muscle cells through
      interleukin-24 (IL-24), with/without TNF-alpha.
AB  - In CKD patients, arteriosclerotic lesions, including calcification, can occur in
      vascular smooth muscle cells in a process called Moenckeberg's medial
      arteriosclerosis. Iron overload induces several complications, including the
      acceleration of arteriosclerosis. However, the relationship between Moenckeberg's
      arteriosclerosis in vascular smooth muscle cells and iron accumulation has
      remained unknown. We tested the accelerated effect of iron on calcification in
      cultured human aortic vascular smooth muscle cells (HASMCs). After establishment
      of this model, we performed a microarray analysis using mRNA from early stage
      culture HASMCs after iron stimulation with or without TNF-alpha stimulation. The
      role of interleukin-24 (IL-24) was confirmed from candidate genes that might
      contribute to calcification. HASMCs demonstrated calcification induced by iron
      and TNF-alpha. Calcification of HASMCs was synergistically enhanced by
      stimulation with both iron and TNF-alpha. In the early phase of calcification,
      microarray analysis revealed up-regulation of IL-24. Stimulation of HASMCs by IL
      24 instead of iron induced calcification. The anti-IL-24 antibody reversed the
      effect of IL-24, supporting the important role of IL-24 in HASMCs calcification.
      In conclusion, iron-induced calcification in vascular smooth muscle cells
      occurred via IL-24, IL-24 was increased during the calcification process induced
      by iron, and IL-24 itself caused calcification in the absence of iron.

PMID- 29330518
TI  - Spartina alterniflora invasion affects soil carbon in a C3 plant-dominated tidal
      marsh.
AB  - The carbon cycle is significantly affected by Spartina alterniflora invasion
      through its impact on blue carbon in many salt marshes. To determine the impacts
      on soil organic carbon (SOC), we studied the vertical and horizontal distribution
      of SOC. And stable carbon isotopes were used to explore the impact of the age of
      S. alterniflora invasion on SOC in Chongming Dongtan wetland located in the
      Yangtze River estuary, China. The results showed that the SOC concentration was
      higher in the S. alterniflora community than that in the native Phragmites
      australis community. The age of invasion and the SOC concentration increased with
      increasing elevation, while the SOC concentration decreased with increasing soil
      depth. The delta13C value became less negative at greater depth, which was
      related to the contribution from 13C- enriched carbon sources after 3 years of
      invasion. After 7 and 10 years, the delta13C value became more negative at
      greater depth in both communities. S. alterniflora had a positive effect on the
      soil carbon pool, and its contribution was related to soil depth. In the low
      tidal marshes, the contribution of S. alterniflora was negatively correlated with
      soil depth, while it was positively correlated with soil depth in the high tidal
      marshes. The results from this study will contribute to improved understanding of
      future ecological consequences.

PMID- 29330519
TI  - Large-scale aggregation analysis of eukaryotic proteins reveals an involvement of
      intrinsically disordered regions in protein folding.
AB  - A subset of the proteome is prone to aggregate formation, which is prevented by
      chaperones in the cell. To investigate whether the basic principle underlying the
      aggregation process is common in prokaryotes and eukaryotes, we conducted a large
      scale aggregation analysis of ~500 cytosolic budding yeast proteins using a
      chaperone-free reconstituted translation system, and compared the obtained data
      with that of ~3,000 Escherichia coli proteins reported previously. Although the
      physicochemical properties affecting the aggregation propensity were generally
      similar in yeast and E. coli proteins, the susceptibility of aggregation in yeast
      proteins were positively correlated with the presence of intrinsically disordered
      regions (IDRs). Notably, the aggregation propensity was not significantly changed
      by a removal of IDRs in model IDR-containing proteins, suggesting that the
      properties of ordered regions in these proteins are the dominant factors for
      aggregate formation. We also found that the proteins with longer IDRs were
      disfavored by E. coli chaperonin GroEL/ES, whereas both bacterial and yeast
      Hsp70/40 chaperones have a strong aggregation-prevention effect even for proteins
      possessing IDRs. These results imply that a key determinant to discriminate the
      eukaryotic proteomes from the prokaryotic proteomes in terms of protein folding
      would be the attachment of IDRs.

PMID- 29330520
TI  - Association of Homocysteine with Aysmptomatic Intracranial and Extracranial
      Arterial Stenosis in Hypertension Patients.
AB  - Elevated plasma homocysteine (Hcy) is suggested as an independent risk factor for
      stroke. We aimed to investigate the association of Hcy concentration with
      intracranial atherosclerosis (ICAS) and extracranial AS (ECAS) in hypertensive
      patients without stroke in Chinese population and to explore modified effect of
      methylenetetrahydrofolate reductase (MTHFR) C677T on their relationship. The
      stenosis of intracranial and extracranial arteries were evaluated in a total of
      929 subjects through computerized tomographic angiography (CTA) from aortic arch
      to the skull base. Hcy concentration showed significantly association with both
      ICAS (OR: 1.105; 95% CI: 1.057-1.155) and ECAS (OR: 1.096; 95% CI: 1.047-1.146)
      for 1 umol/L increment in Hcy. Meanwhile, hyperhomocysteinemia (>=15 umol/L) was
      also displayed association with ICAS (OR: 1.587; 95% CI: 1.029-2.446) and ECAS
      (OR: 2.164; 95% CI: 1.392-3.364) after fully adjustment. Furthermore, in the
      subgroup analysis, such association remained significant only in the subjects
      that were younger, with normal renal function and with MTHFR 677 C allele. Our
      study showed the significant association of Hcy with ECAS and ICAS in
      asymptomatic hypertension patients. Hcy played a universal effect on the cervico
      cerebral atherosclerosis. Such association was modified by the MTHFR C677T
      genotype.

PMID- 29330521
TI  - RGS7 is recurrently mutated in melanoma and promotes migration and invasion of
      human cancer cells.
AB  - Analysis of 501 melanoma exomes revealed RGS7, which encodes a GTPase
      accelerating protein (GAP), to be a tumor-suppressor gene. RGS7 was mutated in
      11% of melanomas and was found to harbor three recurrent mutations (p.R44C,
      p.E383K and p.R416Q). Structural modeling of the most common recurrent mutation
      of the three (p.R44C) predicted that it destabilizes the protein due to the loss
      of an H-bond and salt bridge network between the mutated position and the serine
      and aspartic acid residues at positions 58 as 61, respectively. We experimentally
      confirmed this prediction showing that the p.R44C mutant protein is indeed
      destabilized. We further show RGS7 p.R44C has weaker catalytic activity for its
      substrate Galphao, thus providing a dual mechanism for its loss of function. Both
      of these effects are expected to contribute to loss of function of RGS7 resulting
      in increased anchorage-independent growth, migration and invasion of melanoma
      cells. By mutating position 56 in the R44C mutant from valine to cysteine,
      thereby enabling the formation of a disulfide bridge between the two mutated
      positions, we slightly increased the catalytic activity and reinstated protein
      stability, leading to the rescue of RGS7's function as a tumor suppressor. Our
      findings identify RGS7 as a novel melanoma driver and point to the clinical
      relevance of using strategies to stabilize the protein and, thereby, restore its
      function.

PMID- 29330522
TI  - The RacGAP beta-Chimaerin is essential for cerebellar granule cell migration.
AB  - During mammalian cerebellar development, postnatal granule cell progenitors
      proliferate in the outer part of the External Granule Layer (EGL). Postmitotic
      granule progenitors migrate tangentially in the inner EGL before switching to
      migrate radially inward, past the Purkinje cell layer, to achieve their final
      position in the mature Granule Cell Layer (GCL). Here, we show that the RacGAP
      beta-chimaerin is expressed by a small population of late-born, premigratory
      granule cells. beta-chimaerin deficiency causes a subset of granule cells to
      become arrested in the EGL, where they differentiate and form ectopic neuronal
      clusters. These clusters of granule cells are able to recruit aberrantly
      projecting mossy fibers. Collectively, these data suggest a role for beta
      chimaerin as an intracellular mediator of Cerebellar Granule Cell radial
      migration.

PMID- 29330523
TI  - Closed-loop control of zebrafish behaviour in three dimensions using a robotic
      stimulus.
AB  - Robotics is continuously being integrated in animal behaviour studies to create
      customizable, controllable, and repeatable stimuli. However, few systems have
      capitalized on recent breakthroughs in computer vision and real-time control to
      enable a two-way interaction between the animal and the robot. Here, we present a
      "closed-loop control" system to investigate the behaviour of zebrafish, a popular
      animal model in preclinical studies. The system allows for actuating a
      biologically-inspired 3D-printed replica in a 3D workspace, in response to the
      behaviour of a zebrafish. We demonstrate the role of closed-loop control in
      modulating the response of zebrafish, across a range of behavioural and
      information-theoretic measures. Our results suggest that closed-loop control
      could enhance the degree of biomimicry of the replica, by increasing the
      attraction of live subjects and their interaction with the stimulus. Interactive
      experiments hold promise to advance our understanding of zebrafish, offering new
      means for high throughput behavioural phenotyping.

PMID- 29330526
TI  - Relationship among land surface temperature and LUCC, NDVI in typical karst area.
AB  - Land surface temperature (LST) can reflect the land surface water-heat exchange
      process comprehensively, which is considerably significant to the study of
      environmental change. However, research about LST in karst mountain areas with
      complex topography is scarce. Therefore, we retrieved the LST in a karst mountain
      area from Landsat 8 data and explored its relationships with LUCC and NDVI. The
      results showed that LST of the study area was noticeably affected by altitude and
      underlying surface type. In summer, abnormal high-temperature zones were observed
      in the study area, perhaps due to karst rocky desertification. LSTs among
      different land use types significantly differed with the highest in construction
      land and the lowest in woodland. The spatial distributions of NDVI and LST
      exhibited opposite patterns. Under the spatial combination of different land use
      types, the LST-NDVI feature space showed an obtuse-angled triangle shape and
      showed a negative linear correlation after removing water body data. In summary,
      the LST can be retrieved well by the atmospheric correction model from Landsat 8
      data. Moreover, the LST of the karst mountain area is controlled by altitude,
      underlying surface type and aspect. This study provides a reference for land use
      planning, ecological environment restoration in karst areas.

PMID- 29330524
TI  - NF-kappaB inducing kinase is a therapeutic target for systemic lupus
      erythematosus.
AB  - NF-kappaB-inducing kinase (NIK) mediates non-canonical NF-kappaB signaling
      downstream of multiple TNF family members, including BAFF, TWEAK, CD40, and OX40,
      which are implicated in the pathogenesis of systemic lupus erythematosus (SLE).
      Here, we show that experimental lupus in NZB/W F1 mice can be treated with a
      highly selective and potent NIK small molecule inhibitor. Both in vitro as well
      as in vivo, NIK inhibition recapitulates the pharmacological effects of BAFF
      blockade, which is clinically efficacious in SLE. Furthermore, NIK inhibition
      also affects T cell parameters in the spleen and proinflammatory gene expression
      in the kidney, which may be attributable to inhibition of OX40 and TWEAK
      signaling, respectively. As a consequence, NIK inhibition results in improved
      survival, reduced renal pathology, and lower proteinuria scores. Collectively,
      our data suggest that NIK inhibition is a potential therapeutic approach for SLE.

PMID- 29330525
TI  - Distinct modulation of inactivation by a residue in the pore domain of voltage
      gated Na+ channels: mechanistic insights from recent crystal structures.
AB  - Inactivation of voltage-gated Na+ channels (VGSC) is essential for the regulation
      of cellular excitability. The molecular rearrangement underlying inactivation is
      thought to involve the intracellular linker between domains III and IV serving as
      inactivation lid, the receptor for the lid (domain III S4-S5 linker) and the pore
      lining S6 segements. To better understand the role of the domain IV S6 segment in
      inactivation we performed a cysteine scanning mutagenesis of this region in rNav
      1.4 channels and screened the constructs for perturbations in the voltage
      dependence of steady state inactivation. This screen was performed in the
      background of wild-type channels and in channels carrying the mutation K1237E,
      which profoundly alters both permeation and gating-properties. Of all tested
      constructs the mutation I1581C was unique in that the mutation-induced gating
      changes were strongly influenced by the mutational background. This suggests that
      I1581 is involved in specific short-range interactions during inactivation. In
      recently published crystal structures VGSCs the respective amino acids homologous
      to I1581 appear to control a bend of the S6 segment which is critical to the
      gating process. Furthermore, I1581 may be involved in the transmission of the
      movement of the DIII voltage-sensor to the domain IV S6 segment.

PMID- 29330527
TI  - Aquaglyceroporin PbAQP is required for efficient progression through the liver
      stage of Plasmodium infection.
AB  - The discovery of aquaglyceroporins (AQP) has highlighted a new mechanism of
      membrane solute transport that may hold therapeutic potential for controlling
      parasitic infections, including malaria. Plasmodium parasites express a single
      AQP at the plasma membrane that functions as a channel for water, nutrients and
      waste into and out cells. We previously demonstrated that Plasmodium berghei
      targeted for PbAQP deletion are deficient in glycerol import and less virulent
      than wild-type parasites during the blood developmental stage. Here, we have
      examined the contribution of PbAQP to the infectivity of P. berghei in the liver.
      PbAQP is expressed in the sporozoite mosquito stage and is detected at low levels
      in intrahepatic parasites at the onset of hepatocyte infection. As the parasites
      progress to late hepatic stages, PbAQP transcription increases and PbAQP
      localizes to the plasma membrane of hepatic merozoites. Compared to wild-type
      parasites, PbAQP-null sporozoites exhibit a delay in blood stage infection due to
      slower replication in hepatocytes, resulting in retardation of merosome
      production. Furthermore, PbAQP disruption results in a significant reduction in
      erythrocyte infectivity by hepatocyte-derived merozoites. Hepatic merozoites
      incorporate exogenous glycerol into glycerophospholipids and PbAQP-null
      merozoites contain less phosphatidylcholine than wild-type merozoites,
      underlining the contribution of Plasmodium AQP to phospholipid syntheses.

PMID- 29330528
TI  - Application of Weighted Gene Co-expression Network Analysis for Data from Paired
      Design.
AB  - Investigating how genes jointly affect complex human diseases is important, yet
      challenging. The network approach (e.g., weighted gene co-expression network
      analysis (WGCNA)) is a powerful tool. However, genomic data usually contain
      substantial batch effects, which could mask true genomic signals. Paired design
      is a powerful tool that can reduce batch effects. However, it is currently
      unclear how to appropriately apply WGCNA to genomic data from paired design. In
      this paper, we modified the current WGCNA pipeline to analyse high-throughput
      genomic data from paired design. We illustrated the modified WGCNA pipeline by
      analysing the miRNA dataset provided by Shiah et al. (2014), which contains forty
      oral squamous cell carcinoma (OSCC) specimens and their matched non-tumourous
      epithelial counterparts. OSCC is the sixth most common cancer worldwide. The
      modified WGCNA pipeline identified two sets of novel miRNAs associated with OSCC,
      in addition to the existing miRNAs reported by Shiah et al. (2014). Thus, this
      work will be of great interest to readers of various scientific disciplines, in
      particular, genetic and genomic scientists as well as medical scientists working
      on cancer.

PMID- 29330530
TI  - Estimation of lean body mass by creatinine kinetics increases the prevalence of
      muscle wasting in peritoneal dialysis patients compared to bioimpedance.
AB  - Dialysis patients are at increased risk for muscle wasting, and time efficient
      screening tests are required for to allow for early detection. Creatinine
      kinetics have been advocated to estimate lean body mass (LBM) in peritoneal
      dialysis (PD) patients, and can be readily calculated in clinical practice from
      peritoneal dialysate effluent and urine collections. Bioimpedance is increasingly
      available, and we compared methods in 434 PD patients (55% men, 33.3% diabetics),
      mean age 55.2 +/- 16.2 years. LBM was lower by creatinine kinetics (47.8 +/- 16.6
      kg men, 37.8 +/- 11.2 kg women) vs. bioimpedance (53.2 +/- 11.5 kg men, 39.2 +/-
      7.2 kg women), p < 0.01. The prevalence of muscle wasting was much greater using
      creatinine kinetics (72.4% men, 52.4% women) vs. bioimpedance (55.2% men, 37.3%),
      p < 0.05. Estimates of LBM were much lower using creatinine kinetics compared to
      bioimpedance. Studies reporting the prevalence of muscle loss in PD patients will
      differ depending upon the method used to estimate muscle mass.

PMID- 29330529
TI  - The interaction network of the YidC insertase with the SecYEG translocon, SRP and
      the SRP receptor FtsY.
AB  - YidC/Oxa1/Alb3 are essential proteins that operate independently or cooperatively
      with the Sec machinery during membrane protein insertion in bacteria, archaea and
      eukaryotic organelles. Although the interaction between the bacterial SecYEG
      translocon and YidC has been observed in multiple studies, it is still unknown
      which domains of YidC are in contact with the SecYEG translocon. By in vivo and
      in vitro site-directed and para-formaldehyde cross-linking we identified the
      auxiliary transmembrane domain 1 of E. coli YidC as a major contact site for SecY
      and SecG. Additional SecY contacts were observed for the tightly packed globular
      domain and the C1 loop of YidC, which reveals that the hydrophilic cavity of YidC
      faces the lateral gate of SecY. Surprisingly, YidC-SecYEG contacts were only
      observed when YidC and SecYEG were present at about stoichiometric
      concentrations, suggesting that the YidC-SecYEG contact in vivo is either very
      transient or only observed for a very small SecYEG sub-population. This is
      different for the YidC-SRP and YidC-FtsY interaction, which involves the C1 loop
      of YidC and is efficiently observed even at sub-stoichiometric concentrations of
      SRP/FtsY. In summary, our data provide a first detailed view on how YidC
      interacts with the SecYEG translocon and the SRP-targeting machinery.

PMID- 29330531
TI  - Low density neutrophils (LDN) in postoperative abdominal cavity assist the
      peritoneal recurrence through the production of neutrophil extracellular traps
      (NETs).
AB  - Many types of immune cells appear in peritoneal cavity after abdominal surgery.
      In patients who underwent laparotomy due to gastric cancer, peritoneal lavages
      were obtained before and after surgical procedure. Cells were recovered from
      intermediate layer after Ficoll-Hypaque centrifugation and analyzed for
      phenotypes and functions, especially focused on low density neutrophils (LDN).
      The number of CD66b (+) LDN with mature phenotype was markedly elevated in
      postoperative as compared with preoperative lavages. Short term culture of the
      purified LDN produced many threadlike structures positive for SYTOX, nucleic acid
      staining, as well as histone and myeloperoxidase, suggesting the NETs formation.
      Human gastric cancer cells, MKN45, OCUM-1 and NUGC-4, were selectively attached
      on the NETs, which was totally abolished by the pretreatment of DNAse I.
      Intraperitoneal (IP) co-transfer of the LDN with MKN45 in nude mice strongly
      augments the metastasis formation on peritoneum, which was strongly suppressed by
      the following IP administration of DNAse I. Many NETs-like structures were
      detected on the surface of human omental tissue resected by gastrectomy. NETs on
      peritoneal surface can assist the clustering and growth of free tumor cells
      disseminated in abdomen. Disruption of the NETs by DNAse might be useful to
      prevent the peritoneal recurrence after abdominal surgery.

PMID- 29330532
TI  - Methanobactin from Methylosinus trichosporium OB3b inhibits N2O reduction in
      denitrifiers.
AB  - Methanotrophs synthesize methanobactin, a secondary metabolite that binds copper
      with an unprecedentedly high affinity. Such a strategy may provide methanotrophs
      a "copper monopoly" that can inhibit the activity of copper-containing enzymes of
      other microbes, e.g., copper-dependent N2O reductases. Here, we show that
      methanobactin from Methylosinus trichosporium OB3b inhibited N2O reduction in
      denitrifiers. When Pseudomonas stutzeri DCP-Ps1 was incubated in cocultures with
      M. trichosporium OB3b or with purified methanobactin from M. trichosporium OB3b,
      stoichiometric N2O production was observed from NO3- reduction, whereas no
      significant N2O accumulation was observed in cocultures with a mutant defective
      in methanobactin production. Copper uptake by P. stutzeri DCP-Ps1 was inhibited
      by the presence of purified methanobactin, leading to a significant
      downregulation of nosZ transcription. Similar findings were observed with three
      other denitrifier strains. These results suggest that in situ stimulation of
      methanotrophs can inadvertently increase N2O emissions, with the potential for
      increasing net greenhouse gas emissions.

PMID- 29330533
TI  - Soil contamination alters the willow root and rhizosphere metatranscriptome and
      the root-rhizosphere interactome.
AB  - Phytoremediation using willows is thought to be a sustainable alternative to
      traditional remediation techniques involving excavation, transport, and
      landfilling. However, the complexity of the interaction between the willow and
      its associated highly diverse microbial communities makes the optimization of
      phytoremediation very difficult. Here, we have sequenced the rhizosphere
      metatranscriptome of four willow species and the plant root metatranscriptome for
      two willow species growing in petroleum hydrocarbon-contaminated and non
      contaminated soils on a former petroleum refinery site. Significant differences
      in the abundance of transcripts related to different bacterial and fungal taxa
      were observed between willow species, mostly in contaminated soils. When
      comparing transcript abundance in contaminated vs. non-contaminated soil for each
      willow species individually, transcripts for many microbial taxa and functions
      were significantly more abundant in contaminated rhizosphere soil for Salix
      eriocephala, S. miyabeana and S. purpurea, in contrast to what was observed in
      the rhizosphere of S. caprea. This agrees with the previously reported
      sensitivity of S. caprea to contamination, and the superior tolerance of S.
      miyabeana and S. purpurea to soil contamination at that site. The root
      metatranscriptomes of two species were compared and revealed that plants
      transcripts are mainly influenced by willow species, while microbial transcripts
      mainly responded to contamination. A comparison of the rhizosphere and root
      metatranscriptomes in the S. purpurea species revealed a complete reorganization
      of the linkages between root and rhizosphere pathways when comparing willows
      growing in contaminated and non-contaminated soils, mainly because of large
      shifts in the rhizosphere metatranscriptome.

PMID- 29330534
TI  - When increasing population density can promote the evolution of metabolic
      cooperation.
AB  - Microbial cooperation drives ecological and epidemiological processes and is
      affected by the ecology and demography of populations. Population density
      influences the selection for cooperation, with spatial structure and the type of
      social dilemma, namely public-goods production or self-restraint, shaping the
      outcome. While existing theories predict that in spatially structured
      environments increasing population density can select either for or against
      cooperation, experimental studies with both public-goods production and self
      restraint systems have only ever shown that increasing population density favours
      cheats. We suggest that the disparity between theory and empirical studies
      results from experimental procedures not capturing environmental conditions
      predicted by existing theories to influence the outcome. Our study resolves this
      issue and provides the first experimental evidence that high population density
      can favour cooperation in spatially structured environments for both self
      restraint and public-goods production systems. Moreover, using a multi-trait
      mathematical model supported by laboratory experiments we extend this result to
      systems where the self-restraint and public-goods social dilemmas interact. We
      thus provide a systematic understanding of how the strength of interaction
      between the two social dilemmas and the degree of spatial structure within an
      environment affect selection for cooperation. These findings help to close the
      current gap between theory and experiments.

PMID- 29330535
TI  - The stoichiometry of coral-dinoflagellate symbiosis: carbon and nitrogen cycles
      are balanced in the recycling and double translocation system.
AB  - Symbioses between microalgae and animal hosts have the advantage of acquiring and
      sharing autotrophically produced organic carbon (C) as their energy source.
      However, the stoichiometry and turnover rates of biological elements in symbioses
      are not fully understood because of complicated metabolic interactions. We report
      the first comprehensive and simultaneous measurement of C and nitrogen (N) flows
      through coral-dinoflagellate symbiosis by using the unique approach of dual
      isotope labeling with 13C and 15N, in situ chasing, and isotope-mixing models.
      The coral autotrophy occurred with much lower C:N ratios than previously thought,
      and the autotrophically produced N-rich organic matter was efficiently
      transferred to the animal host through two different pathways. In contrast to the
      dynamic N cycles within the symbiosis, the N uptake from the ambient seawater was
      extremely limited, which enabled the coral symbiosis to sustain N with a long
      turnover time (1 year). These findings suggest that coral endosymbionts are not
      under N limitation but are actively producing organic N and driving microscale N
      cycles in the reef ecosystem. The present techniques could be applied to further
      quantify the C and N cycles in other symbiotic interactions and reveal their
      ecological advantages.

PMID- 29330537
TI  - Tracing the role of human civilization in the globalization of plant pathogens.

PMID- 29330536
TI  - Carbon limitation drives GC content evolution of a marine bacterium in an
      individual-based genome-scale model.
AB  - An important unanswered question in evolutionary genomics is the source of
      considerable variation of genomic base composition (GC content) even among
      organisms that share one habitat. Evolution toward GC-poor genomes has been
      considered a major adaptive pathway in the oligotrophic ocean, but GC-rich
      bacteria are also prevalent and highly successful in this environment. We
      quantify the contribution of multiple factors to the change of genomic GC content
      of Ruegeria pomeroyi DSS-3, a representative and GC-rich member in the globally
      abundant Roseobacter clade, using an agent-based model. The model simulates 2 *
      108 cells, which allows random genetic drift to act in a realistic manner. Each
      cell has a whole genome subject to base-substitution mutation and recombination,
      which affect the carbon and nitrogen requirements of DNA and protein pools.
      Nonsynonymous changes can be functionally deleterious. Together, these factors
      affect the growth and fitness. Simulations show that experimentally determined
      mutation bias toward GC is not sufficient to build the GC-rich genome of DSS-3.
      While nitrogen availability has been repeatedly hypothesized to drive the
      evolution of GC content in marine bacterioplankton, our model instead predicts
      that DSS-3 and its ancestors have been evolving in environments primarily limited
      by carbon.

PMID- 29330538
TI  - Flux of the biogenic volatiles isoprene and dimethyl sulfide from an oligotrophic
      lake.
AB  - Biogenic volatile organic compounds (BVOCs) affect atmospheric chemistry, climate
      and regional air quality in terrestrial and marine atmospheres. Although isoprene
      is a major BVOC produced in vascular plants, and marine phototrophs release
      dimethyl sulfide (DMS), lakes have been widely ignored for their production. Here
      we demonstrate that oligotrophic Lake Constance, a model for north temperate deep
      lakes, emits both volatiles to the atmosphere. Depth profiles indicated that
      highest concentrations of isoprene and DMS were associated with the chlorophyll
      maximum, suggesting that their production is closely linked to phototrophic
      processes. Significant correlations of the concentration patterns with taxon
      specific fluorescence data, and measurements from algal cultures confirmed the
      phototrophic production of isoprene and DMS. Diurnal fluctuations in lake
      isoprene suggested an unrecognised physiological role in environmental
      acclimation similar to the antioxidant function of isoprene that has been
      suggested for marine biota. Flux estimations demonstrated that lakes are a
      currently undocumented source of DMS and isoprene to the atmosphere. Lakes may be
      of increasing importance for their contribution of isoprene and DMS to the
      atmosphere in the arctic zone where lake area coverage is high but terrestrial
      sources of BVOCs are small.

PMID- 29330540
TI  - Author Correction: REST regulates the cell cycle for cardiac development and
      regeneration.
AB  - The original version of this Article contained an error in the spelling of the
      author Jianyun Yan, which was incorrectly given as Jiangyun Yan. This has now
      been corrected in both the PDF and HTML versions of the Article.

PMID- 29330539
TI  - Missing Value Imputation Approach for Mass Spectrometry-based Metabolomics Data.
AB  - Missing values exist widely in mass-spectrometry (MS) based metabolomics data.
      Various methods have been applied for handling missing values, but the selection
      can significantly affect following data analyses. Typically, there are three
      types of missing values, missing not at random (MNAR), missing at random (MAR),
      and missing completely at random (MCAR). Our study comprehensively compared eight
      imputation methods (zero, half minimum (HM), mean, median, random forest (RF),
      singular value decomposition (SVD), k-nearest neighbors (kNN), and quantile
      regression imputation of left-censored data (QRILC)) for different types of
      missing values using four metabolomics datasets. Normalized root mean squared
      error (NRMSE) and NRMSE-based sum of ranks (SOR) were applied to evaluate
      imputation accuracy. Principal component analysis (PCA)/partial least squares
      (PLS)-Procrustes analysis were used to evaluate the overall sample distribution.
      Student's t-test followed by correlation analysis was conducted to evaluate the
      effects on univariate statistics. Our findings demonstrated that RF performed the
      best for MCAR/MAR and QRILC was the favored one for left-censored MNAR. Finally,
      we proposed a comprehensive strategy and developed a public-accessible web-tool
      for the application of missing value imputation in metabolomics (
      https://metabolomics.cc.hawaii.edu/software/MetImp/ ).

PMID- 29330541
TI  - 19F-perfluorocarbon-labeled human peripheral blood mononuclear cells can be
      detected in vivo using clinical MRI parameters in a therapeutic cell setting.
AB  - A 19Fluorine (19F) perfluorocarbon cell labeling agent, when employed with an
      appropriate cellular MRI protocol, allows for in vivo cell tracking. 19F cellular
      MRI can be used to non-invasively assess the location and persistence of cell
      based cancer vaccines and other cell-based therapies. This study was designed to
      determine the feasibility of labeling and tracking peripheral blood mononuclear
      cells (PBMC), a heterogeneous cell population. Under GMP-compliant conditions
      human PBMC were labeled with a 19F-based MRI cell-labeling agent in a manner safe
      for autologous re-injection. Greater than 99% of PBMC labeled with the 19F cell
      labeling agent without affecting functionality or affecting viability. The 19F
      labeled PBMC were detected in vivo in a mouse model at the injection site and in
      a draining lymph node. A clinical cellular MR protocol was optimized for the
      detection of PBMC injected both at the surface of a porcine shank and at a depth
      of 1.2 cm, equivalent to depth of a human lymph node, using a dual 1H/19F dual
      switchable surface radio frequency coil. This study demonstrates it is feasible
      to label and track 19F-labeled PBMC using clinical MRI protocols. Thus, 19F
      cellular MRI represents a non-invasive imaging technique suitable to assess the
      effectiveness of cell-based cancer vaccines.

PMID- 29330542
TI  - Regulation of metabolism in Escherichia coli during growth on mixtures of the non
      glucose sugars: arabinose, lactose, and xylose.
AB  - Catabolite repression refers to the process where the metabolism of one sugar
      represses the genes involved in metabolizing another sugar. While glucose
      provides the canonical example, many other sugars are also known to induce
      catabolite repression. However, less is known about the mechanism for catabolite
      repression by these non-glucose sugars. In this work, we investigated the
      mechanism of catabolite repression in the bacterium Escherichia coli during
      growth on lactose, L-arabinose, and D-xylose. The metabolism of these sugars is
      regulated in a hierarchical manner, where lactose is the preferred sugar,
      followed by L-arabinose, and then D-xylose. Previously, the preferential
      utilization of L-arabinose over D-xylose was found to result from transcriptional
      crosstalk. However, others have proposed that cAMP governs the hierarchical
      regulation of many non-glucose sugars. We investigated whether lactose-induced
      repression of L-arabinose and D-xylose gene expression is due to transcriptional
      crosstalk or cAMP. Our results demonstrate that it is due to cAMP and not
      transcriptional crosstalk. In addition, we found that repression is reciprocal,
      where both L-arabinose and D-xylose also repress the lactose gene expression,
      albeit to a lesser extent and also through a mechanism involving cAMP.
      Collectively, the results further our understanding of metabolism during growth
      on multiple sugars.

PMID- 29330544
TI  - Perceptions of legislation relating to the sharing of genomic biobank results
      with donors-a survey of BBMRI-ERIC biobanks.
AB  - Biobanks accumulate huge amounts of research findings, including participants'
      genomic data. Increasingly this leads to biobanks receiving research results that
      could be of clinical significance to biobank participants. The EU Horizon 2020
      Project 'Genetics Clinic of the Future' surveyed European biobanks' perceptions
      of the legal and regulatory requirements for communicating individual research
      results to donors. The goal was to gain background knowledge for possible future
      guidelines, especially relating to the consent process. The Survey was
      implemented using a web-based Webropol tool. The questionnaire was sent at the
      end of 2015 to 351 European biobanks in 13 countries that are members of BBMRI
      ERIC (Biobanking and Biomolecular Resources Research Infrastructure-European
      Research Infrastructure Consortium). Seventy-two biobanks responded to the
      survey, representing each of the 13 BBMRI Member States. Respondents were mainly
      individuals responsible for the governance of biobanks. The replies indicate that
      the majority of the respondents thought that their national legislation allowed
      them to contact participants to communicate results, and that research
      participants had the right to request their results. However, respondents'
      understanding of their national legislation varied even within member states. Our
      results indicate that legislation applied to biobanks in many countries may be
      scattered and difficult to interpret. In BBMRI-ERIC, there is an ongoing
      discussion about the need for European recommendations on sharing genomic biobank
      results with donors, which may pave the way for more coherent global guidelines.
      Our results form a basis for this work.

PMID- 29330543
TI  - CUGC for Duchenne muscular dystrophy (DMD).

PMID- 29330545
TI  - De novo BK channel variant causes epilepsy by affecting voltage gating but not
      Ca2+ sensitivity.
AB  - Epilepsy is one of the most common neurological diseases and it causes profound
      morbidity and mortality. We identified the first de novo variant in KCNMA1
      (c.2984 A > G (p.(N995S)))-encoding the BK channel-that causes epilepsy, but not
      paroxysmal dyskinesia, in two independent families. The c.2984 A > G (p.(N995S))
      variant markedly increased the macroscopic potassium current by increasing both
      the channel open probability and channel open dwell time. The c.2984 A > G
      (p.(N995S)) variant did not affect the calcium sensitivity of the channel. We
      also identified three other variants of unknown significance (c.1554 G > T
      (p.(K518N)), c.1967A > C (p.(E656A)), and c.3476 A > G (p.(N1159S))) in three
      separate patients with divergent epileptic phenotypes. However, these variants
      did not affect the BK potassium current, and are therefore unlikely to be disease
      causing. These results demonstrate that BK channel variants can cause epilepsy
      without paroxysmal dyskinesia. The underlying molecular mechanism can be
      increased activation of the BK channel by increased sensitivity to the voltage
      dependent activation without affecting the sensitivity to the calcium-dependent
      activation. Our data suggest that the BK channel may represent a drug target for
      the treatment of epilepsy. Our data highlight the importance of functional
      electrophysiological studies of BK channel variants in distinguishing whether a
      genomic variant of unknown significance is a disease-causing variant or a benign
      variant.

PMID- 29330546
TI  - Older mothers and increased impact of prenatal screening: stable livebirth
      prevalence of trisomy 21 in the Netherlands for the period 2000-2013.
AB  - In the Netherlands, there is no registry system regarding the livebirth
      prevalence of trisomy 21 (T21). In 2007, a national screening programme was
      introduced for all pregnant women, which may have changed the livebirth
      prevalence of T21. The aim of this study is to analyse trends in factors that
      influence livebirth prevalence of T21 and to estimate the livebirth prevalence of
      T21 for the period of 2000-2013. National data sets were used on the following:
      (1) livebirths according to maternal age and (2) prenatal testing and termination
      of pregnancy (ToP) following diagnosis of T21. These data are combined in a model
      that uses maternal age-specific risk on T21 and correction factors for natural
      foetal loss to assess livebirth prevalence of T21. The proportion of mothers aged
      >= 36 years has increased from 12.2% in 2000 to 16.6% in 2009, to gradually
      decrease afterwards to 15.2% in 2013. The number of invasive tests performed
      adjusted for total livebirths decreased (5.9% in 2000 vs. 3.2% in 2013) with
      0.18% a year (95% CI: -0.21 to -0.15; p   < 0.001). Following invasive testing, a
      higher proportion of foetuses was diagnosed with T21 (1.6% in 2000 vs. 4.8% in
      2013) with a significant increase of 0.22% a year (95% CI: 0.18-0.26; p < 0.001).
      The proportion of ToP subsequent to T21 diagnosis was on average 85.7%, with no
      clear time trend. This resulted in a stable T21 livebirth prevalence of 13.6 per
      10,000 livebirths (regression coefficient -0.025 (95% CI: -0.126 to 0.77; p =
      0.60).

PMID- 29330547
TI  - Recessive loss of function PIGN alleles, including an intragenic deletion with
      founder effect in La Reunion Island, in patients with Fryns syndrome.
AB  - Fryns syndrome (FS) is a multiple malformations syndrome with major features of
      congenital diaphragmatic hernia, pulmonary hypoplasia, craniofacial dysmorphic
      features, distal digit hypoplasia, and a range of other lower frequency
      malformations. FS is typically lethal in the fetal or neonatal period.
      Inheritance is presumed autosomal recessive. Although no major genetic cause has
      been identified for FS, biallelic truncating variants in PIGN, encoding a
      component of the glycosylphosphatidylinositol (GPI)-anchor biosynthesis pathway,
      have been identified in a limited number of cases with a phenotype compatible
      with FS. Biallelic variants in PIGN, typically missense or compound missense with
      truncating, also cause multiple congenital anomalies-hypotonia-seizures syndrome
      1 (MCAHS1). Here we report six further patients with FS with or without
      congenital diaphragmatic hernia and recessive loss of function PIGN alleles,
      including an intragenic deletion with a likely founder effect in La Reunion and
      other Indian Ocean islands. Our results support the hypothesis that a spectrum of
      phenotypic severity is associated with recessive PIGN variants, ranging from FS
      at the extreme end, caused by complete loss of function, to MCAHS1, in which some
      residual PIGN function may remain. Our data add FS resulting from PIGN variants
      to the catalog of inherited GPI deficiencies caused by the disruption of the GPI
      anchor biosynthesis pathway.

PMID- 29330549
TI  - Excellent room temperature deformability in high strain rate regimes of magnesium
      alloy.
AB  - Magnesium and its alloys have the lowest density among structural metallic
      materials; thus, this light-weight metal has great potential for reducing the
      weight, for example, of vehicles and trains. However, due to its crystal
      structure, deformability is poor; in particular, under compressive stress. In
      this study, we modified magnesium with bismuth as an alloying element, which has
      the characteristics of being likely to form precipitates instead of grain
      boundary segregation. The Mg-Bi binary alloy showed excellent deformability and
      high absorption of energy in high-strain rate regimes at room temperature via
      contribution of grain boundary sliding. These properties, which are closely
      comparable to those of conventional middle-strength aluminum alloys (Al-Mg and Al
      Mg-Si series alloys), have never been observed before in magnesium alloys. The
      development of such properties opens the door for not only academic but also
      industrial research in magnesium.

PMID- 29330548
TI  - SHOX haploinsufficiency presenting with isolated short long bones in the second
      and third trimester.
AB  - Haploinsufficiency of the transcription factor short stature homeobox (SHOX)
      manifests as a spectrum of clinical phenotypes, ranging from disproportionate
      short stature and Madelung deformity to isolated short stature. Here, we describe
      five infants with molecularly confirmed diagnoses of SHOX haploinsufficiency who
      presented in utero with short long bones during routine antenatal scanning from
      as early as 19 weeks gestation. Other foetal growth parameters were normal. The
      molecular basis of SHOX haploinsufficiency was distinct in each case. In four
      cases, SHOX haploinsufficiency was inherited from a previously undiagnosed
      parent. In our de novo case, SHOX haploinsufficiency reflected the formation of a
      derivative sex chromosome during paternal meiosis. Final adult height in the SHOX
      deficient parents ranged from -1.9 to -1.2 SDS. All affected parents had
      disproportionately short limbs and two affected mothers had bilateral Madelung
      deformity. To our knowledge, SHOX haploinsufficiency has not previously been
      reported to present in utero. Our experience illustrates that SHOX deficiency
      should form part of the differential diagnosis of foetal short long bones and
      suggests a low threshold for genetic testing. This should be particularly
      targeted at, but not limited to, families with a history of features suggestive
      of SHOX deficiency. Data on the postnatal growth of our index cases is presented
      which demonstrates that antenatal presentation of SHOX haploinsufficiency is not
      indicative of severe postnatal growth restriction. Early identification of SHOX
      deficiency will enable accurate genetic counselling reflecting a good postnatal
      outcome and facilitate optimal initiation of growth hormone therapy.

PMID- 29330553
TI  - Remote Microphone System Use at Home: Impact on Caregiver Talk.
AB  - Purpose: The purpose of this study was to investigate the effects of home use of
      a remote microphone system (RMS) on the spoken language production of caregivers
      with young children who have hearing loss. Method: Language Environment Analysis
      recorders were used with 10 families during 2 consecutive weekends (RMS weekend
      and No-RMS weekend). The amount of talk from a single caregiver that could be
      made accessible to children with hearing loss when using an RMS was estimated
      using Language Environment Analysis software. The total amount of caregiver talk
      (close and far talk) was also compared across both weekends. In addition,
      caregivers' perceptions of RMS use were gathered. Results: Children, with the use
      of RMSs, could potentially have access to approximately 42% more words per day.
      In addition, although caregivers produced an equivalent number of words on both
      weekends, they tended to talk more from a distance when using the RMS than when
      not. Finally, caregivers reported positive perceived communication benefits of
      RMS use. Conclusions: Findings from this investigation suggest that children with
      hearing loss have increased access to caregiver talk when using an RMS in the
      home environment. Clinical implications and future directions for research are
      discussed.

PMID- 29330551
TI  - Autapses promote synchronization in neuronal networks.
AB  - Neurological disorders such as epileptic seizures are believed to be caused by
      neuronal synchrony. However, to ascertain the causal role of neuronal
      synchronization in such diseases through the traditional approach of
      electrophysiological data analysis remains a controversial, challenging, and
      outstanding problem. We offer an alternative principle to assess the
      physiological role of neuronal synchrony based on identifying structural
      anomalies in the underlying network and studying their impacts on the collective
      dynamics. In particular, we focus on autapses - time delayed self-feedback links
      that exist on a small fraction of neurons in the network, and investigate their
      impacts on network synchronization through a detailed stability analysis. Our
      main finding is that the proper placement of a small number of autapses in the
      network can promote synchronization significantly, providing the computational
      and theoretical bases for hypothesizing a high degree of synchrony in real
      neuronal networks with autapses. Our result that autapses, the shortest possible
      links in any network, can effectively modulate the collective dynamics provides
      also a viable strategy for optimal control of complex network dynamics at minimal
      cost.

PMID- 29330552
TI  - Dosimetry Prediction for Clinical Translation of 64Cu-Pembrolizumab ImmunoPET
      Targeting Human PD-1 Expression.
AB  - The immune checkpoint programmed death 1 receptor (PD-1) expressed on some tumor
      infiltrating lymphocytes, and its ligand (PD-L1) expressed on tumor cells, enable
      cancers to evade the immune system. Blocking PD-1 with the monoclonal antibody
      pembrolizumab is a promising immunotherapy strategy. Thus, noninvasively
      quantifying the presence of PD-1 expression in the tumor microenvironment prior
      to initiation of immune checkpoint blockade may identify the patients likely to
      respond to therapy. We have developed a 64Cu-pembrolizumab radiotracer and
      evaluated human dosimetry. The tracer was utilized to image hPD-1 levels in two
      subcutaneous mouse models: (a) 293 T/hPD-1 cells xenografted into NOD-scid IL
      2Rgammanull mice (NSG/293 T/hPD-1) and (b) human peripheral blood mononuclear
      cells engrafted into NSG bearing A375 human melanoma tumors (hNSG/A375). In each
      mouse model two cohorts were evaluated (hPD-1 blockade with pembrolizumab [blk]
      and non-blocked [nblk]), for a total of four groups (n = 3-5/group). The
      xenograft-to-muscle ratio in the NSG/293 T/hPD-1 model at 24 h was significantly
      increased in the nblk group (7.0 +/- 0.5) compared to the blk group (3.4 +/-
      0.9), p = 0.01. The radiotracer dosimetry evaluation (PET/CT ROI-based and ex
      vivo) in the hNSG/A375 model revealed the highest radiation burden to the liver.
      In summary, we validated the 64Cu-pembrolizumab tracer's specific hPD-1 receptor
      targeting and predicted human dosimetry.

PMID- 29330550
TI  - A Metabolomics Pilot Study on Desmoid Tumors and Novel Drug Candidates.
AB  - Desmoid tumors (aggressive fibromatosis) are locally invasive soft tissue tumors
      that lack the ability to metastasize. There are no directed therapies or standard
      treatment plan, and chemotherapeutics, radiation, and surgery often have
      temporary effects. The majority of desmoid tumors are related to T41A and S45F
      mutations of the beta-catenin encoding gene (CTNNB1). Using broad spectrum
      metabolomics, differences were investigated between paired normal fibroblast and
      desmoid tumor cells from affected patients. There were differences identified,
      also, in the metabolomics profiles associated with the two beta-catenin
      mutations, T41A and S45F. Ongoing drug screening has identified currently
      available compounds which inhibited desmoid tumor cellular growth by more than
      50% but did not affect normal fibroblast proliferation. Two drugs were
      investigated in this study, and Dasatinib and FAK Inhibitor 14 treatments
      resulted in unique metabolomics profiles for the normal fibroblast and desmoid
      tumor cells, in addition to the T41A and S45F. The biochemical pathways that
      differentiated the cell lines were aminoacyl-tRNA biosynthesis in mitochondria
      and cytoplasm and signal transduction amino acid-dependent mTORC1 activation.
      This study provides preliminary understanding of the metabolic differences of
      paired normal and desmoid tumors cells, their response to desmoid tumor
      therapeutics, and new pathways to target for therapy.

PMID- 29330554
TI  - Accuracy of a Screening Tool for Early Identification of Language Impairment.
AB  - Purpose: A screening tool called the VTO Language Screening Instrument (VTO-LSI)
      was developed to enable more uniform and earlier detection of language
      impairment. This report, consisting of 2 retrospective studies, focuses on the
      effects of using the VTO-LSI compared to regular detection procedures. Method:
      Study 1 retrospectively compared VTO-LSI with regular detection procedures.
      Outcome measure was the detection rate of language impairment among 24-month-old
      children. Data were retrieved from medical records of children attending a youth
      health care center. Study 2 retrospectively compared the effects of VTO-LSI and
      regular detection procedures on the age at referral for diagnostic investigations
      and the influence of sex. Data were retrieved from medical records from the
      speech and hearing center and analyzed with multivariate analysis of variance.
      Results: With the VTO-LSI, significantly more cases with language impairment were
      identified compared with the regular detection procedure (2.4% vs. 0.4%). In
      regions where the VTO-LSI was used, girls were almost 2 years younger, and boys
      were 1 year younger when referred to diagnostic investigations than in regions
      with regular detection procedures. Conclusion: The VTO-LSI was more effective
      than regular detection procedures.

PMID- 29330555
TI  - Performance of Low-Income Dual Language Learners Attending English-Only Schools
      on the Clinical Evaluation of Language Fundamentals-Fourth Edition, Spanish.
AB  - Purpose: The aim of this study was to examine the performance of a group of
      Spanish-speaking, dual language learners (DLLs) who were attending English-only
      schools and came from low-income and low-parental education backgrounds on the
      Clinical Evaluation of Language Fundamentals-Fourth Edition, Spanish (CELF-4S;
      Semel, Wiig, & Secord, 2006). Method: Spanish-speaking DLLs (N = 656), ages 5;0
      (years;months) to 7;11, were tested for language impairment (LI) using the core
      language score of the CELF-4S and the English Structured Photographic Expressive
      Language Test (Dawson, Stout, & Eyer, 2003). A subsample (n = 299) was
      additionally tested using a Spanish language sample analysis and a newly
      developed Spanish morphosyntactic measure, for identification of children with LI
      and to conduct a receiver operating characteristics curve analysis. Results: Over
      50% of the sample scored more than 1 SD below the mean on the core language
      score. In our subsample, the sensitivity of the CELF-4S was 94%, and specificity
      was 65%, using a cutoff score of 85 as suggested in the manual. Using an
      empirically derived cutoff score of 78, the sensitivity was 86%, and the
      specificity was 80%. Conclusions: Results suggest that the CELF-4S overidentifies
      low-income Spanish-English DLLs attending English-only schools as presenting with
      LI. For this sample, 1 in every 3 Latino children from low socioeconomic status
      was incorrectly identified with LI. Clinicians should be cautious when using the
      CELF-4S to evaluate low-income Spanish-English DLLs and ensure that they have
      converging evidence before making diagnostic decisions.

PMID- 29330556
TI  - Evolution of the Phosphatidylcholine Biosynthesis Pathways in Green Algae:
      Combinatorial Diversity of Methyltransferases.
AB  - Phosphatidylcholine (PC) is one of the most common phospholipids in eukaryotes,
      although some green algae such as Chlamydomonas reinhardtii are known to lack PC.
      Recently, we detected PC in four species in the genus Chlamydomonas: C. applanata
      NIES-2202, C. asymmetrica NIES-2207, C. debaryana NIES-2212, and C. sphaeroides
      NIES-2242. To reveal the PC biosynthesis pathways in green algae and the
      evolutionary scenario involved in their diversity, we analyzed the PC
      biosynthesis genes in these four algae using draft genome sequences. Homology
      searches suggested that PC in these species is synthesized by phosphoethanolamine
      N-methyltransferase (PEAMT) and/or phosphatidylethanolamine-N-methyltransferase
      (PEMT), both of which are absent in C. reinhardtii. Recombinant PEAMTs from these
      algae showed methyltransferase activity for phosphoethanolamine but not for
      monomethyl phosphoethanolamine in vitro, in contrast to land plant PEAMT, which
      catalyzes the three methylations from phosphoethanolamine to phosphocholine. This
      suggested an involvement of other methyltransferases in PC biosynthesis. Here, we
      characterized the putative phospholipid-N-methyltransferase (PLMT) genes of these
      species by genetic and phylogenetic analysis. Complementation assays using a PC
      biosynthesis-deficient yeast suggested that the PLMTs of these algae can
      synthesize PC from phosphatidylethanolamine. These results indicated that the PC
      biosynthesis pathways in green algae differ from those of land plants, although
      the enzymes involved are homologous. Phylogenetic analysis suggested that the
      PEAMTs and PLMTs in these algae were inherited from the common ancestor of green
      algae. The absence of PC biosynthesis in many Chlamydomonas species is likely a
      result of parallel losses of PEAMT and PLMT in this genus.

PMID- 29330557
TI  - Linear doggybone DNA vaccine induces similar immunological responses to
      conventional plasmid DNA independently of immune recognition by TLR9 in a pre
      clinical model.
AB  - Vaccination with DNA that encodes cancer antigens is a simple and convenient way
      to raise immunity against cancer and has already shown promise in the clinical
      setting. Conventional plasmid DNA is commonly used which together with the
      encoded antigen also includes bacterial immunostimulatory CpG motifs to target
      the DNA sensor Toll-like receptor 9. Recently DNA vaccines using doggybone DNA
      (dbDNATM), have been developed without the use of bacteria. The cell-free process
      relies on the use of Phi29 DNA polymerase to amplify the template followed by
      protelomerase TelN to complete individual closed linear DNA. The resulting DNA
      contains the required antigenic sequence, a promoter and a poly A tail but lacks
      bacterial sequences such as an antibiotic resistance gene, prompting the question
      of immunogenicity. Here we compared the ability of doggybone DNA vaccine with
      plasmid DNA vaccine to induce adaptive immunity using clinically relevant
      oncotargets E6 and E7 from HPV. We demonstrate that despite the inability to
      trigger TLR9, doggybone DNA was able to induce similar levels of cellular and
      humoral immunity as plasmid DNA, with suppression of established TC-1 tumours.

PMID- 29330558
TI  - Variant of a persistent hypoglossal artery supplying only the posterior inferior
      cerebellar artery diagnosed by magnetic resonance angiography: a case report.
AB  - Very rarely, a persistent hypoglossal artery supplies only the posterior inferior
      cerebellar artery without connection to the basilar artery. Few cases diagnosed
      by catheter angiography have been reported. We diagnosed a case using magnetic
      resonance angiography.

PMID- 29330559
TI  - A post-translational balancing act: the good and the bad of SUMOylation in
      pancreatic islets.
AB  - Post-translational modification of proteins contributes to the control of cell
      function and survival. The balance of these in insulin-producing pancreatic beta
      cells is important for the maintenance of glucose homeostasis. Protection from
      the damaging effects of reactive oxygen species is required for beta cell
      survival, but if this happens at the expense of insulin secretory function then
      the ability of islets to respond to changing metabolic conditions may be
      compromised. In this issue of Diabetologia, He et al (
      https://doi.org/10.1007/s00125-017-4523-9 ) show that post-translational
      attachment of small ubiquitin-like modifier (SUMO) to target lysine residues
      (SUMOylation) strikes an important balance between the protection of beta cells
      from oxidative stress and the maintenance of insulin secretory function. They
      show that SUMOylation is required to stabilise nuclear factor erythroid 2-related
      factor 2 (NRF2) and increase antioxidant gene expression. Decreasing SUMOylation
      in beta cells impairs their antioxidant capacity, causes cell death,
      hyperglycaemia, and increased sensitivity to streptozotocin-induced diabetes,
      while increasing SUMOylation is protective. However, this protection from overt
      diabetes occurs in concert with glucose intolerance due to impaired beta cell
      function. A possible role for SUMOylation as a key factor balancing beta cell
      protection vs beta cell responsiveness to metabolic cues is discussed in this
      Commentary.

PMID- 29330562
TI  - Influence of genetic polymorphisms of IL23R, STAT3, IL12B, and STAT4 on the risk
      of aplastic anemia and the effect of immunosuppressive therapy.
AB  - Studies have suggested that IL-23/STAT3 and IL-12/STAT4 signaling pathways
      associate with aplastic anemia (AA) occurrence. Polymorphisms in pathway-related
      genes may contribute to AA risk. In the current study, we investigated the
      association between polymorphisms in genes of IL23R, STAT3, IL12B, and STAT4 and
      occurrence, severity, and immunosuppressive outcome of AA in the Han population
      in southwest China. In the current 164 AA cases and 211 controls study, we found
      T allele and TT genotype of rs7574865 were more frequent in the cases than that
      in the controls. In the additive model, individual carrying rs7574865 T allele
      demonstrated a 37% (OR (95% CI) = 1.37 (1.02-1.85), Pper = 0.036) increased AA
      risk. In the recessive model, carrier with rs7574865 TT genotype showed a 2.08
      fold increased AA risk (OR (95% CI) = 2.08 (1.14-3.70), Pper = 0.017).
      Additionally, we showed that G allele and GG genotype of rs11209032 were more
      frequent in the 88 non-severe AA cases than that in the 76 severe AA ones. Our
      study also found G allele and GG genotype of rs11209032, and GG-genotype of
      rs744166 associated with the immunosuppressive therapy outcome in AA patients.
      Current study results support that functional STAT4 (rs7574865), IL23R
      (rs11209032), and STAT3 (rs744166) variants may associate with occurrence,
      severity, and immunosuppressive outcome of AA in the Han population in southwest
      China.

PMID- 29330563
TI  - Serious concerns on the inability of FDG-PET in excluding residual viable
      lymphoma.

PMID- 29330560
TI  - Altered Bone Remodeling in Psoriatic Disease: New Insights and Future Directions.
AB  - Psoriatic arthritis (PsA) is an inflammatory rheumatic disorder that occurs in
      patients with psoriasis and predominantly affects musculoskeletal structures,
      skin, and nails. The etiology of PsA is not well understood but evidence supports
      an interplay of genetic, immunologic, and environmental factors which promote
      pathological bone remodeling and joint damage in PsA. Localized and systemic bone
      loss due to increased activity of osteoclasts is well established in PsA based on
      animal models and translational studies. In contrast, the mechanisms responsible
      for pathological bone remodeling in PsA remain enigmatic although new candidate
      molecules and pathways have been identified. Recent reports have revealed novel
      findings related to bone erosion and pathologic bone formation in PsA. Many
      associated risk factors and contributing molecular mechanisms have also been
      identified. In this review, we discuss new developments in the field, point out
      unresolved questions regarding the pathogenetic origins of the wide array of bone
      phenotypes in PsA, and discuss new directions for investigation.

PMID- 29330561
TI  - Salvage therapy post pomalidomide-based regimen in relapsed/refractory myeloma.
AB  - The combination of pomalidomide and low-dose dexamethasone (Pom-Dex) has proved
      effective and safe in patients with end-stage relapsed/refractory multiple
      myeloma (RRMM), otherwise characterized by a very poor outcome. MM remains an
      incurable disease with unavoidable relapses, and the outcome after pomalidomide
      is still dismal. However, some patients demonstrate prolonged survival even
      beyond pomalidomide therapy.We sought to analyze the treatment of RRMM patients
      following Pom-Dex therapy and the response and survival after this next treatment
      line.We studied 134 patients treated with Pom-Dex until progression across two
      IFM studies. Seventy percent of these patients received further therapy after Pom
      Dex. Among the treated patients, one third responded and one third maintained
      stable disease. The median OS for treated patients was 12 months (6.5;17), with
      22 and 12.5% of patients surviving beyond 2 and 3 years, respectively. The
      factors associated with a better outcome were exposure to a triplet-based regimen
      containing a novel agent, response to therapy, absence of adverse cytogenetic,
      and a longer time from diagnosis to post pomalidomide therapy.This study suggests
      that patients relapsing after Pom-Dex therapy can still benefit from a further
      line of treatment. A subset of these treated patients even displayed a prolonged
      OS, while the prognosis remained very poor without treatment. An active approach
      could therefore be recommended even in this adverse situation, however guided by
      the patients' prognosis factors.

PMID- 29330571
TI  - Impact of motor task execution on an individual's ability to mirror forearm
      positions.
AB  - This work is motivated by our goal of determining why individuals with stroke are
      impaired when locating their arms in space. We assessed the ability of
      individuals without neurological impairments to mirror their forearms during
      various motor tasks so that we could identify baseline performance in an
      unimpaired population. Nine right-hand dominant participants without neurological
      impairments mirrored forearm positions bi-directionally (i.e., right forearm
      mirrors left forearm, vice versa) for three motor tasks (i.e., passive,
      passive/active, and active) and two position identification modes (i.e.,
      mirroring to a position stored in working memory versus concurrently felt by the
      opposite arm). During each trial, the participant's reference forearm moved to a
      flexion ([Formula: see text]) or extension ([Formula: see text]) position, and
      then, their opposite forearm mirrored the position of their reference forearm.
      The main finding across all tested conditions is that participants mirrored
      forearm positions with an average magnitude of error [Formula: see text]. When
      controlling their forearms' movements (active motor task), participants mirrored
      forearm positions more accurately by up to, on average, [Formula: see text] at
      the flexion location than at the extension location. Moreover, participants
      mirrored forearm positions more accurately by up to, on average, [Formula: see
      text] when their forearms were moved for them rather than when they controlled
      their forearms' movements. Task directionality and position identification mode
      did not significantly affect participant arm mirroring accuracy. These findings
      are relevant for interpreting in future work the reason why impairments occur, on
      similar tasks, in individuals with altered motor commands, working memory, and
      arm impedance, e.g., post-stroke hemiparesis.

PMID- 29330570
TI  - Open-door laminoplasty : What can the unilateral approach offer?
AB  - OBJECTIVE: Multilevel posterior decompression of subaxial cervical spinal canal
      stenosis through a less-invasive unilateral approach. INDICATIONS: Degenerative
      cervical myelopathy due to multilevel subaxial spinal canal stenosis.
      CONTRAINDICATIONS: Cervical kyphosis or instability, bilateral radiculopathy due
      to foraminal stenosis, involvement of C2 or C7. SURGICAL TECHNIQUE: Unilateral
      subaxial approach with detachment of muscles only on one side. The ipsilateral
      laminae C6 to C3 are cut at the laminofacet junction and opened up. The loss of
      resistance is usually due to a greenstick fracture in the proximity of the
      contralateral laminofacet junction. The opened laminae are fixed with Z-shaped
      thin titanium plates. If necessary, the laminoplasty can be combined with a
      unilateral fixation and fusion by the same approach. POSTOPERATIVE MANAGEMENT:
      Early mobilization 4-6 h postoperatively. No orthosis necessary. RESULTS: A total
      of 131 patients (77 men, mean age 67 years) with a multilevel cervical
      spondylotic myelopathy (CSM) underwent surgery using a posterior approach. In 52
      patients (40%), a unilateral approach was performed (laminoplasty: n = 30;
      laminoplasty/fusion: n = 22). In this group, the mean operation time was less
      compared with two other techniques (unilateral approach: 110 min;
      laminectomy/fusion: 150 min; 360 degrees  approach: 210 min). The postoperative
      European myelopathy score (EMS) improved from 12.8 to 15.2. The overall
      complication rate was 17% (unilateral approach: 9%; laminectomy/fusion: 18%; 360
      degrees  approach: 27%).

PMID- 29330572
TI  - Effects of whole-body vibration on muscle strength, bone mineral content and
      density, and balance and body composition of children and adolescents with Down
      syndrome: a systematic review.
AB  - The aim of this study is to verify the effects of whole-body vibration (WBV)
      training on the muscle strength of children and adolescents with Down syndrome.
      We searched MEDLINE, Cochrane, SciELO, Lilacs and PUBMED databases and included
      manual searches to identify randomised controlled trials to investigate the
      effects of WBV on the structure and body function of children and adolescents
      with Down syndrome. Two reviewers independently selected the studies and
      performed statistical analysis. In total, five studies with 171 patients that
      compared WBV with exercise and/or control were included. Two studies demonstrated
      a significant difference between the muscle strength of children and adolescents
      with Down syndrome who received WBV training and that of those who did not
      receive the intervention. The studies included in this systematic review showed
      that WBV training has positive effects on bone mineral density (BMD), body
      composition and balance. Results of this study showed that WBV training improves
      muscle strength, BMD, body composition and balance of children and adolescents
      with Down syndrome, and a more in-depth analysis of its effects on other
      variables in this population is required, as well as of parameters to be used.

PMID- 29330573
TI  - Tocotrienol supplementation suppressed bone resorption and oxidative stress in
      postmenopausal osteopenic women: a 12-week randomized double-blinded placebo
      controlled trial.
AB  - : Tocotrienols have shown bone-protective effect in animals. This study showed
      that a 12-week tocotrienol supplementation decreased concentrations of bone
      resorption biomarker and bone remodeling regulators via suppressing oxidative
      stress in postmenopausal osteopenic women. INTRODUCTION: Tocotrienols (TT) have
      been shown to benefit bone health in ovariectomized animals, a model of
      postmenopausal women. The purpose of this study was to evaluate the effect of 12
      week TT supplementation on bone markers (serum bone-specific alkaline phosphatase
      (BALP), urine N-terminal telopeptide (NTX), serum soluble receptor activator of
      nuclear factor-kappaB ligand (sRANKL), and serum osteoprotegerin (OPG)), urine
      calcium, and an oxidative stress biomarker (8-hydroxy-2'-deoxyguanosine (8-OHdG))
      in postmenopausal women with osteopenia. METHODS: Eighty-nine postmenopausal
      osteopenic women (59.7 +/- 6.8 year, BMI 28.7 +/- 5.7 kg/m2) were randomly
      assigned to three groups: (1) placebo (430 mg olive oil/day), (2) low TT (430 mg
      TT/day, 70% purity), and (3) high TT (860 mg TT/day, 70% purity). TT, an extract
      from annatto seed with 70% purity, consisted of 90% delta-TT and 10% gamma-TT.
      Overnight fasting blood and urine samples were collected at baseline, 6, and 12
      weeks for biomarker analyses. Eighty-seven subjects completed the 12-week study.
      RESULTS: Relative to the placebo group, there were marginal decreases in serum
      BALP level in the TT-supplemented groups over the 12-week study period.
      Significant decreases in urine NTX levels, serum sRANKL, sRANKL/OPG ratio, and
      urine 8-OHdG concentrations and a significant increase in BALP/NTX ratio due to
      TT supplementation were observed. TT supplementation did not affect serum OPG
      concentrations or urine calcium levels throughout the study period. There were no
      significant differences in NTX level, BALP/NTX ratio, sRANKL level, and
      sRANKL/OPG ratio between low TT and high TT groups. CONCLUSIONS: Twelve-week
      annatto-extracted TT supplementation decreased bone resorption and improved bone
      turnover rate via suppressing bone remodeling regulators in postmenopausal women
      with osteopenia. Such osteoprotective TT's effects may be, in part, mediated by
      an inhibition of oxidative stress. TRIAL REGISTRATION: ClinicalTrials.gov
      identifier: NCT02058420. TITLE: Tocotrienols and bone health of postmenopausal
      women.

PMID- 29330574
TI  - Ectomycorrhizal fungal communities in alpine relict forests of Pinus pumila on
      Mt. Norikura, Japan.
AB  - Ectomycorrhizal (ECM) symbioses are indispensable for the establishment of host
      trees, yet available information of ECM symbiosis in alpine forests is scarce.
      Pinus pumila is a typical ice age relict tree species in Japan and often forms
      monodominant dwarf vegetation above the tree line in mountains. We studied ECM
      fungi colonizing P. pumila on Mt. Norikura, Japan, with reference to host
      developmental stages, i.e., from current-year seedlings to mature trees. ECM
      fungal species were identified based on rDNA ITS sequences. Ninety-two ECM fungal
      species were confirmed from a total of 2480 root tips examined. Species in
      /suillus-rhizopogon and /wilcoxina were dominant in seedling roots. ECM fungal
      diversity increased with host development, due to the addition of species-rich
      fungal lineages (/cenococcum, /cortinarius, and /russula-lactarius) in late
      successional stages. Such successional pattern of ECM fungi is similar to those
      in temperate pine systems, suggesting the predominant role of /suillus-rhizopogon
      in seedling establishment, even in relict alpine habitats fragmented and isolated
      for a geological time period. Most of the ECM fungi detected were also recorded
      in Europe or North America, indicating their potential Holarctic distribution and
      the possibility of their comigration with P. pumila through land bridges during
      ice ages. In addition, we found significant effects of soil properties on ECM
      fungal communities, which explained 34.1% of the total variation of the fungal
      communities. While alpine vegetation is regarded as vulnerable to the ongoing
      global warming, ECM fungal communities associated with P. pumila could be altered
      by the edaphic change induced by the warming.

PMID- 29330575
TI  - A new technique for minimal invasive complete spinal cord injury in minipigs.
AB  - BACKGROUND: The aim of this study was to develop a minimal invasive complete
      spinal cord injury (SCI) minipig model for future research applications. The
      minipig is considered a translationally relevant model for SCI research. However,
      a standardized minimal invasive complete SCI model for pigs has not yet been
      established. METHODS: Adult Gottingen minipigs were anesthetized and placed in
      extended prone position. After initial computed tomography (CT) scan, the skin
      was incised, a needle placed in the epidural fatty tissue. Using the Seldinger
      technique, a guidewire and dilators were introduced to insert the balloon
      catheter to Th12. After confirmation of the level Th11/Th12, the balloon was
      inflated to 2 atm for 30 min. The severity of the lesion was followed by CT and
      by MRI, and by immunohistochemistry. Function was assessed at the motor and
      sensory level. RESULTS: Duration of procedure was about 60 min including the 30
      min compression time. The balloon pressure of 2 atm was maintained without
      losses. The lesion site was clearly discernible and no intradural bleeding was
      observed by CT. Neurological assessments during the 4-month follow-up time showed
      consistent, predictable, and stable neurological deficits. Magnetic resonance
      imaging analyses at 6 h and 4 weeks post SCI with final immunohistochemical
      analyses of spinal cord tissue underlined the neurological outcomes and proved
      SCI completeness. CONCLUSIONS: We have established a new, minimal invasive,
      highly standardized, CT-guided spinal cord injury procedure for minipigs. All
      risks of the open surgery can be excluded using this technique. This CT-guided SC
      compression is an excellent technique as it avoids long surgery and extensive
      trauma and allows a feasible inter-animal comparison.

PMID- 29330576
TI  - Xipho-pubic angle (XPA) correlates with patient's reported outcomes in a
      population of adult spinal deformity: results from a multi-center cohort study.
AB  - STUDY DESIGN: Retrospective multi-center cohort study. PURPOSE: Sagittal
      misalignment causes changes in the abdominal shape. Xipho-pubic angle (XPA) has
      been previously described to radiographically evaluate the shape of the abdominal
      cavity in patients with spine deformity. The aims of this study are to evaluate
      the correlation of XPA-to-spinopelvic sagittal parameters and to patients' health
      related quality-of-life (HRQoL) scores. METHODS: 278 patients from a multi-center
      database with diagnosis adult spinal deformity (ASD) (one or more of: coronal
      Cobb angle > 20 degrees , sagittal vertical axis (SVA) > 50 mm, pelvic tilt (PT)
      > 25 degrees , and thoracic kyphosis > 60 degrees ) were included. Cut-off values
      for moderate and severe disability (ODI-Oswestry Disability Index-20 and 40%)
      were calculated. Pearson's correlation was tested between XPA and spinopelvic
      parameters and between XPA and HRQoL scores. RESULTS: The cut-off value of XPA to
      identify ODI severe disability (40/100) was identified with XPA smaller than 103
      degrees ; minimal (20/100) disability was identified by XPA greater than 113
      degrees . XPA showed strong correlation to sagittal spinopelvic parameters-PT,
      SVA, lumbar lordosis (LL), pelvic incidence (PI) minus LL-and to HRQoL scores
      ODI, SF-36 PCS and SRS-22 activity and pain. XPA was the parameter with the
      strongest correlation to HRQoL scores. CONCLUSIONS: Xipho-pubic angle reflects
      changes in spinal changes and has strong correlation to HRQoL and spinopelvic
      parameters. It can discriminate between patients with minimal, moderate, and
      severe disability as measured by ODI scores. These slides can be retrieved under
      Electronic Supplementary Material.

PMID- 29330578
TI  - [Lichenoid diseases].

PMID- 29330577
TI  - Asymptomatic population reference values for three knee patient-reported outcomes
      measures: evaluation of an electronic data collection system and implications for
      future international, multi-centre cohort studies.
AB  - OBJECTIVES: The aim was to assess whether the Knee Society Score, Oxford Knee
      Score (OKS) and Knee Injury and Osteoarthritis Outcome Score (KOOS) were
      comparable in asymptomatic, healthy, individuals of different age, gender and
      ethnicity, across two remote continents. The purpose of this study was to
      establish normal population values for these scores using an electronic data
      collection system. HYPOTHESIS: There is no difference in clinical knee scores in
      an asymptomatic population when comparing age, gender and ethnicity, across two
      remote continents. METHODS: 312 Australian and 314 Canadian citizens, aged 18-94
      years, with no active knee pain, injury or pathology in the ipsilateral knee
      corresponding to their dominant arm, were evaluated. A knee examination was
      performed and participants completed an electronically administered questionnaire
      covering the subjective components of the knee scores. The cohorts were age- and
      gender-matched. Chi-square tests, Fisher's exact test and Poisson regression
      models were used where appropriate, to investigate the association between knee
      scores, age, gender, ethnicity and nationality. RESULTS: There was a significant
      inverse relationship between age and all assessment tools. OKS recorded a
      significant difference between gender with females scoring on average 1% lower
      score. There was no significant difference between international cohorts when
      comparing all assessment tools. CONCLUSIONS: An electronic, multi-centre data
      collection system can be effectively utilized to assess remote international
      cohorts. Differences in gender, age, ethnicity and nationality should be taken
      into consideration when using knee scores to compare to pathological patient
      scores. This study has established an electronic, normal control group for future
      studies using the Knee society, Oxford, and KOOS knee scores. LEVEL OF EVIDENCE:
      Diagnostic Level II.

PMID- 29330579
TI  - [Initially undetected de novo psoriasis triggered by nivolumab for metastatic
      base of the tongue carcinoma].
AB  - Nivolumab is a monoclonal antibody that binds to the PD-1 receptor on T cells and
      inhibits the interaction with the PD-L1 and PD-L2 ligands on cancer cells. Thus,
      nivolumab has immunostimulatory properties. The known side effects of this
      therapy include fatigue, skin rash, dysfunction of the thyroid gland and colitis,
      which are explained by the immunoregulatory mechanisms of the drug. Here we
      report on the case of a 58-year-old man with metastatic base of tongue carcinoma
      who developed de novo psoriasis triggered by nivolumab. The patient was treated
      for months with the diagnosis of a generalized mycosis. This case highlights the
      importance of vigilance for unexpected cutaneous side effects during immune
      stimulating therapy with checkpoint inhibitors.

PMID- 29330580
TI  - [Lichen ruber planus : Better understanding, better treatment!]
AB  - Lichen ruber, also called lichen ruber planus or lichen planus (LP), is a
      noncontagious inflammatory skin disease. LP is the main representative and
      namesake of the group of lichenoid diseases, which are characterized by small
      papules often accompanied by severe itching. With 65% of cases, LP is primarily a
      disease of the mucous membranes. In 20% of the cases, the disease is found on the
      skin and mucous membranes; skin involvement alone is seen in only about 10% of
      cases. Cutaneous LP has a very favorable 1-year prognosis of almost 80% healing
      as opposed to the mucosa and the adnexal organs. Histologically, keratinocytes
      with vacuolar degeneration, leaving behind apoptotic Kamino bodies and the
      characteristic band-shaped lymphocytic infiltrate at the dermatoepithelial
      junction, are common to lichenoid diseases. The horny layer is firm and compact
      and the stratum granulosum is thickened as a correlate of the Wickham stripes.
      The molecular pathogenesis, still partially hypothetical, assumes trigger factors
      leading to the presentation of intrinsic or foreign antigens. The triggered
      inflammation becomes independent in the sense of a classical cell-mediated
      autoimmune disease. Other autoimmune diseases are often associated with LP.
      Classical anti-inflammatory-immunosuppressive therapeutic concepts dominate with
      systemic retinoids ranking first in the highest evidence class for cutaneous LP
      with limitations in treatment of both mucosal and adnexal LP. More recently,
      interesting and new complementary phototherapeutics have been identified.

PMID- 29330581
TI  - [Liposuction].
AB  - Liposuction began in the 1920s when the Parisian surgeon Charles Dujarier became
      interested in body shaping and fat removal. Today, it is estimated that 1,453,000
      liposuctions are annually performed worldwide. In Germany, 45,000 liposuctions
      are performed annually. The majority of liposuctions are performed as self-pay
      services. The aim of this article is to outline the development of liposuction,
      to explain the various liposuction procedures and methods, to clarify the
      indications for treatment, and point out the complications and pitfalls described
      in the literature.

PMID- 29330583
TI  - Utilization of Active Surveillance and Watchful Waiting for localized prostate
      cancer in the daily practice.
AB  - PURPOSE: To analyze the utilization of Active Surveillance (AS) and Watchful
      Waiting (WW) in the daily routine setting, since both are non-invasive treatment
      options for localized prostate cancer (PCa), which are used in a curative (AS) or
      palliative (WW) setting. Since differentiation of both strategies is not always
      clear, patients were compared with respect to the inclusion criteria, frequency
      of follow-up examinations (Prostate Specific Antigen = PSA tests, rebiopsies),
      and initiation of a deferred treatment. METHODS: HAROW is a non-interventional,
      health-service research study on the management of localized PCa in the community
      setting. Of 3169 patients, prospectively enrolled from 2008 to 2013 with a mean
      follow-up of 28.2 months, 468 chose AS and 126 WW. Treating urologists reported
      clinical variables, information on therapy and clinical course of disease.
      RESULTS: AS patients were significantly younger and had more low-risk tumors. No
      differences were seen in the number of PSA tests during follow-up: mean number of
      PSA tests was 6.08 for AS- and 5.18 for WW patients, more than four PSA tests
      were reported in 63.9% AS- and 59.5% WW patients (p = 0.136). At least one re
      biopsy was performed in 39.7% AS- and 9.5% WW patients (p < 0.001).
      Discontinuation rates were 23.9% (n = 112) for AS and 11.9% (n = 15) for WW. Most
      of the AS patients opted for a curative treatment (prostatectomy = 65,
      radiotherapy = 30), whereas 12 WW patients received a palliative hormone therapy
      and three patients received radiotherapy. CONCLUSIONS: Physicians seem to
      distinguish clearly between AS and WW in terms of inclusion criteria and deferred
      therapy, whereas this differentiation tends to become indistinct in terms of
      follow-up examinations.

PMID- 29330582
TI  - Nano-silicon alters antioxidant activities of soybean seedlings under salt
      toxicity.
AB  - Materials with a particle size less than 100 nm are classified as nano-materials.
      The physical and chemical properties of nano-materials can vary considerably from
      those of bulk materials of the same composition. Silicon (Si) still fails to get
      recognized as an essential nutrient for plant growth and development, however the
      beneficial effects in terms of growth, biotic and abiotic stress resistance have
      been indicated in a variety of plant species for their growth. The aim of this
      study was to investigate the effects of different nano-silicon rates on the
      growth and antioxidant activities of soybean (Glycine max L. cv. M7) under salt
      stress. The results showed that salinity decreased shoot and root dry weight,
      potassium (K+) concentration in the root and leaf; however, increased sodium
      (Na+) concentration, catalase, peroxidase, ascorbate peroxidase and superoxide
      dismutase activities, phenolic components, ascorbic acid and alpha-tocopherol
      contents, lipid peroxidation, hydrogen peroxide, and oxygen radical's
      concentration. Between the treatments, 0.5 and 1 mM of nanosilicon oxide (nano
      SiO2) improved shoot and root growth of seedlings. In contrast, a foliar
      application of SiO2 at 2 mM reduced the soybean growth. Overall, exogenous nano
      silicon alleviated the salt stress by increase in K+ concentration, antioxidant
      activities, non-enzymatic compounds and decreasing of Na+ concentration, lipid
      peroxidation, and reactive oxygen species production.

PMID- 29330584
TI  - A dedicated neurologist at the emergency department during out-of-office hours
      decreases patients' length of stay and admission percentages.
AB  - BACKGROUND: Emergency departments (EDs) worldwide face crowding, which hampers
      patient flow. In this study, the impact of a dedicated neurologist present at the
      ED on patient flow during out-of-office hours was assessed. METHODS: A cross
      sectional, mixed methods study was undertaken at a Dutch ED, including a pre-post
      analysis of data of patients who had a primary neurological disease (n = 458) and
      staff surveys (n = 152). Descriptive statistics and content analysis were used
      for analyses. RESULTS: Despite a 36% increase in the number of neurological
      patients (control period: n = 194, intervention period n = 264), a 30 min per
      patient decrease in ED median length of stay (LOS) was reached during the
      intervention period. Furthermore, the admission percentage decreased
      significantly (57.7% in the control period vs. 47.7% in the intervention period,
      p = 0.03). During half of the shifts neurologists stated that their presence had
      been valuable. Perceived reasons for this added value mentioned were improved
      quality of care, enhanced throughput of patients, and quicker consultations with
      other medical specialists. CONCLUSIONS: In our hypothesis-generating study, a
      dedicated neurologist present at the ED during out-of-office hours was associated
      with decreased patients' LOS and a decreased admission percentage, indicating
      increased decisiveness when the neurologist is present at the ED.

PMID- 29330586
TI  - Hydrocephalus recurrence and intestinal obstruction due to giant CSF pseudocyst.

PMID- 29330585
TI  - Potentially inappropriate medications in community-dwelling older adults
      undertaken as a comprehensive geriatric risk assessment.
AB  - PURPOSE: The prescription of potentially inappropriate medications (PIMs) is
      associated with an increase in adverse events, prescribing cascades, high health
      care costs, morbidity, and mortality in the elderly. The overarching objective of
      this study is to examine the prevalence of PIMs in the elderly, applying the 2012
      American Geriatrics Society Beers criteria for the study period 2012-2014, and
      the updated 2015 Beers criteria for 2015. METHODS: The study population (N =
      70,479) included a continuously recruited national cohort of community-dwelling
      older (aged >= 65 years) New Zealanders who had undertaken the International
      Resident Assessment Instrument-Home Care (interRAI-HC) assessments between
      September 2012 and October 2015. Exposure of PIMs 90 days before and after
      assessment, and 90-180 days after assessment are reported. RESULTS: Exposure to
      PIMs was highest in individuals aged over 95 years and in males. The average
      number of PIMs prescribed 90 days before assessment during the period 2015 was
      marginally higher compared to 2012-2014 (0.19 versus 0.04), and a greater number
      of individuals were exposed to one or more PIMs in 2015 compared to 2012-2014
      (7.13 versus 2.17%). The prevalence of PIMs 90 days before and after assessment
      was 2.17 and 6.92% for 2012-2014, and 7.13 and 24.7% for 2015, respectively. The
      percent change in PIMs in 2012-2014 and 2015 after 90 days of assessment were
      4.70% (confidence interval (CI) 4.50%, 5.00%, p < 0.001) and 17.60% (95% CI
      16.80%, 18.30%, p < 0.001), respectively. The majority of PIMs prescribed
      belonged to the therapeutic class of medications acting on the central nervous
      system and the gastrointestinal system. CONCLUSION: Geriatric risk assessments
      may provide a vital opportunity to review medication lists by multidisciplinary
      teams with a view to reducing PIMs and unnecessary polypharmacy in older adults.
      Comprehensive geriatric risk assessment has the potential to reduce adverse
      medication outcomes and costs associated with inappropriate prescribing in a
      vulnerable population of older adults.

PMID- 29330587
TI  - Posterior reversible encephalopathy syndrome with spinal cord involvement (PRES
      SCI) as a rare complication of severe diabetic ketoacidosis: a case report and
      review of the literature.
AB  - INTRODUCTION: In addition to diffuse brain oedema, diabetic ketoacidosis (DKA)
      can lead to ischaemic or haemorrhagic stroke, extrapontine myelinolysis, and
      sinovenous thrombosis. However, posterior reversible encephalopathy syndrome
      (PRES) and spinal cord oedema are rarely reported in patients with DKA. METHODS:
      We present a case of a 17-year-old-girl who developed headache, blurred vision,
      and paraplegia after her DKA was controlled. Sequential magnetic resonance (MR)
      scans of the brain and spinal cord were performed. RESULTS: Brain MR showed large
      patchy lesions in the bilateral white matter of the parieto-occipital lobes,
      which had high T2 signal intensity and low T1 signal intensity. MR scanning of
      the spinal cord showed longitudinal confluent central spinal cord T2
      hyperintensity spanning seven thoracic spinal segments. With symptomatic
      treatment, the patient's headache and vision disturbance subsided within 1 week.
      Subsequent MR scans demonstrated that the lesion in the spinal cord had decreased
      significantly in 10 days, and the large patchy lesions in the brain disappeared
      completely in 2 months. Her paraplegia improved gradually without obvious sequela
      3 months later. The evolution of the disease and radiological findings supported
      the diagnosis of PRES with spinal cord involvement. CONCLUSION: To the best of
      our knowledge, this is the first case report describing PRES with spinal cord
      involvement as a complication of DKA. PRES is a rare complication that should be
      considered along with other neurological complications of DKA when focal deficits
      appear.

PMID- 29330588
TI  - Whole-body 3D kinematics of bird take-off: key role of the legs to propel the
      trunk.
AB  - Previous studies showed that birds primarily use their hindlimbs to propel
      themselves into the air in order to take-off. Yet, it remains unclear how the
      different parts of their musculoskeletal system move to produce the necessary
      acceleration. To quantify the relative motions of the bones during the
      terrestrial phase of take-off, we used biplanar fluoroscopy in two species of
      birds, diamond dove (Geopelia cuneata) and zebra finch (Taeniopygia guttata). We
      obtained a detailed 3D kinematics analysis of the head, the trunk and the three
      long bones of the left leg. We found that the entire body assisted the production
      of the needed forces to take-off, during two distinct but complementary phases.
      The first one, a relatively slow preparatory phase, started with a movement of
      the head and an alignment of the different groups of bones with the future take
      off direction. It was associated with a pitch down of the trunk and a flexion of
      the ankle, of the hip and, to a lesser extent, of the knee. This crouching
      movement could contribute to the loading of the leg muscles and store elastic
      energy that could be released in the propulsive phase of take-off, during the
      extension of the leg joints. Combined with the fact that the head, together with
      the trunk, produced a forward momentum, the entire body assisted the production
      of the needed forces to take-off. The second phase was faster with mostly
      horizontal forward and vertical upward translation motions, synchronous to an
      extension of the entire lower articulated musculoskeletal system. It led to the
      propulsion of the bird in the air with a fundamental role of the hip and ankle
      joints to move the trunk upward and forward. Take-off kinematics were similar in
      both studied species, with a more pronounced crouching movement in diamond dove,
      which can be related to a large body mass compared to zebra finch.

PMID- 29330589
TI  - Impact of valve-less vs. standard insufflation on pneumoperitoneum volume,
      inflammation, and peritoneal physiology in a laparoscopic sigmoid resection
      experimental model.
AB  - BACKGROUND: Standard insufflators compensate for intra-abdominal pressure
      variations with pressure spikes. Our aim was to evaluate the impact of a stable,
      low-pressure pneumoperitoneum induced by a valve-less insufflator, on working
      space, hemodynamics, inflammation, and peritoneal physiology, in a model of
      laparoscopic sigmoid resection. MATERIALS AND METHODS: Twelve pigs (47 +/- 3.3
      kg) were equipped for invasive hemodynamic monitoring and randomly assigned to
      Standard (n = 6) vs. valve-less (n = 6) insufflation. Animals were positioned in
      a 30 degrees  Trendelenburg on a CT scan bed. A low-pressure pneumoperitoneum (8
      mmHg) was started and duration was set for 180 min. Abdominal CT scans were
      performed, under neuromuscular blockade, before, immediately after, and 1 and 3 h
      after insufflation. Pneumoperitoneum volumes were calculated on 3D reconstructed
      CT scans. After creation of a mesenteric window, capillary blood was obtained by
      puncturing the sigmoid serosa and local lactatemia (mmol/L) was measured using a
      handheld analyzer. Surgical resection was performed according to the level of
      lactates, in order to standardize bowel stump perfusion. IL-1 and IL-6 (ng/mL)
      were measured repeatedly. The peritoneum was sampled close to the surgical site
      and distantly for the oxygraphic assessment of mitochondrial respiration. A
      pathologist applied a semi-quantitative score to evaluate the anastomosis.
      RESULTS: Mean arterial pressure, pulse, body temperature, oximetry, systemic
      lactatemia, and local lactates were similar. IL-6 was lower in the valve-less
      group, reaching a statistically significant difference after 3 h of insufflation
      (64.85 +/- 32.5 vs. 133.95 +/- 59.73; p = 0.038) and 48 h (77.53 +/- 68.4 vs.
      190.74 +/- 140.79; p = 0.029). Peritoneal mitochondrial respiration was
      significantly increased after the survival period, with no difference among the
      groups. The anastomoses in the valve-less group demonstrated a lower acute (p =
      0.04) inflammatory infiltration. The mean anterior posterior thickness was
      slightly, yet significantly higher in the valve-less group, on all post
      insufflation CT scans. CONCLUSIONS: Valve-less insufflation achieved a slightly
      higher working space and a lower systemic and localized inflammatory response in
      this experimental setting.

PMID- 29330590
TI  - A meta-analysis of pesticide loss in runoff under conventional tillage and no
      till management.
AB  - Global agricultural intensification has led to increased pesticide use (37-fold
      from 1960 to 2005) and soil erosion (14% since 2000). Conservation tillage,
      including no-till (NT), has been proposed as an alternative to conventional plow
      till (PT) to mitigate soil erosion, but past studies have reported mixed results
      on the effect of conservation tillage on pesticide loss. To explore the
      underlying factors of these differences, a meta-analysis was conducted using
      published data on pesticide concentration and load in agricultural runoff from NT
      and PT fields. Peer-reviewed articles (1985-2016) were compiled to build a
      database for analysis. Contrary to expectations, results showed greater
      concentration of atrazine, cyanazine, dicamba, and simazine in runoff from NT
      than PT fields. Further, we observed greater load of dicamba and metribuzin, but
      reduced load of alachlor from NT fields. Overall, the concentration and the load
      of pesticides were greater in runoff from NT fields, especially pesticides with
      high solubility and low affinity for solids. Thus, NT farming affects soil
      properties that control pesticide retention and interactions with soils, and
      ultimately their mobility in the environment. Future research is needed for a
      more complete understanding of pesticide-soil interactions in NT systems. This
      research could inform the selection of pesticides by farmers and improve the
      predictive power of pesticide transport models.

PMID- 29330592
TI  - Genomic characterization of key bacteriophages to formulate the potential
      biocontrol agent to combat enteric pathogenic bacteria.
AB  - Combating bacterial pathogens has become a global concern especially when the
      antibiotics and chemical agents are failing to control the spread due to its
      resistance. Bacteriophages act as a safe biocontrol agent by selectively lysing
      the bacterial pathogens without affecting the natural beneficial microflora. The
      present study describes the screening of prominent enteric pathogens NDK1, NDK2,
      NDK3, and NDK4 (Escherichia, Klebsiella, Enterobacter, and Serratia) mostly
      observed in domestic wastewater; against which KNP1, KNP2, KNP3, and KNP4 phages
      were isolated. To analyze their potential role in eradicating enteric pathogens
      and toxicity issue, these bacteriophages were sequenced using next-generation
      sequencing and characterized based on its genomic content. The isolated
      bacteriophages were homologous to Escherichia phage (KNP1), Klebsiella phage
      (KNP2), Enterobacter phage (KNP3), Serratia phage (KNP4), and belonged to
      Myoviridae family of Caudovirales except for the unclassified KNP4 phage. Draft
      genome analysis revealed the presence of lytic enzymes such as holing and
      lysozyme in KNP1 phage, endolysin in KNP2 phage, and endopeptidase with holin in
      KNP3 phage. The absence of any lysogenic and virulent genes makes this
      bacteriophage suitable candidate for preparation of phage cocktail to combat the
      pathogens present in wastewater. However, KNP4 contained a virulent gene
      rendering it unsuitable to be used as a biocontrol agent. These findings make the
      phages (KNP1-KNP3) as a promising alternative for the biocontrol of pathogens in
      wastewater which is the main culprit to spread these dominated pathogens in
      different natural water bodies. This study also necessitates for genomic
      screening of bacteriophages for lysogenic and virulence genes prior to its use as
      a biocontrol agent.

PMID- 29330593
TI  - The Pathophysiological Basis and Surgical Management of Ranula are Established:
      Reply.

PMID- 29330591
TI  - Changes in the lipopolysaccharide of Proteus mirabilis 9B-m (O11a) clinical
      strain in response to planktonic or biofilm type of growth.
AB  - The impact of planktonic and biofilm lifestyles of the clinical isolate Proteus
      mirabilis 9B-m on its lipopolysaccharide (O-polysaccharide, core region, and
      lipid A) was evaluated. Proteus mirabilis bacteria are able to form biofilm and
      lipopolysaccharide is one of the factors involved in the biofilm formation.
      Lipopolysaccharide was isolated from planktonic and biofilm cells of the
      investigated strain and analyzed by SDS-PAGE with silver staining, Western
      blotting and ELISA, as well as NMR and matrix-assisted laser desorption
      ionization time-of-flight mass spectrometry techniques. Chemical and NMR
      spectroscopic analyses revealed that the structure of the O-polysaccharide of P.
      mirabilis 9B-m strain did not depend on the form of cell growth, but the full
      length chains of the O-antigen were reduced when bacteria grew in biofilm. The
      study also revealed structural modifications of the core region in the
      lipopolysaccharide of biofilm-associated cells-peaks assigned to compounds absent
      in cells from the planktonic culture and not previously detected in any of the
      known Proteus core oligosaccharides. No differences in the lipid A structure were
      observed. In summary, our study demonstrated for the first time that changes in
      the lifestyle of P. mirabilis bacteria leads to the modifications of their
      important virulence factor-lipopolysaccharide.

PMID- 29330594
TI  - Coding valence in touchscreen interactions: hand dominance and lateral movement
      influence valence appraisals of emotional pictures.
AB  - The Body-Specificity Hypothesis postulates that the space surrounding the
      dominant hand is perceived as positive due to the motor fluency of this hand,
      whereas the space surrounding the non-dominant hand is perceived as negative.
      Experimental studies based on this theoretical framework also revealed
      associations between affective valence and hand dominance (i.e., dominant hand
      positive; non-dominant hand-negative), or lateral movements of the hands (i.e.,
      right hand toward the right space-positive; left hand toward the left space
      positive). Interestingly, these associations have not been examined with regard
      to how lateral actions of the hands may influence affective experiences as, for
      example, in valence appraisals of affective objects that have been manipulated.
      The study presented here has considered this question in light of the emerging
      interest of embodied cognition approaches to interactive technologies,
      particularly in affective experiences with touchscreen interfaces. Accordingly,
      right-handed participants evaluated the valence of positive and negative
      emotional pictures after interacting with them either with the dominant right or
      with the non-dominant left hand. Specifically, they moved the pictures either
      from left to right or from right to left sides of a touchscreen monitor. The
      results indicated that a valence matching between the hand used for the
      interactions, the picture's valence category, and the movement's starting side
      reinforced the valence appraisals of the pictures (i.e., positive/negative
      pictures were more positively/negatively evaluated). The findings are discussed
      against the background of the Theory of Event Coding, which accounts for both the
      affective properties of the stimuli and the affective connotation of the related
      action.

PMID- 29330595
TI  - Consistency, not speed: temporal regularity as a metacognitive cue.
AB  - We examined the hypothesis that skilled performance is monitored on the basis of
      fluency, where fluency is operationally defined as temporal regularity or
      rhythmicity rather than speed. Since error is often associated with variable
      timing, we tested the possibility that people use varied timing as a
      metacognitive cue. Using a sequential counting task, which may be representative
      of the broader class of skilled, multi-step tasks, we found that shifting between
      irregular and regular timing led to greater confidence ratings when the timing
      associated with the task was regular. We argue that regular, consistent timing,
      when compared directly to irregular timing, produced feelings of fluent task
      performance, leading to increased confidence. In the first experiment, we
      demonstrated that both accuracy and confidence were higher when participants
      completed a task presented with regular timing. In the second experiment, we
      found a dissociation between accuracy and confidence, strengthening the argument
      that individuals relied on monitoring of fluency to support their metacognitive
      judgments. In Study 3 and an assessment of naive beliefs, we ruled out
      alternative explanations for these findings.

PMID- 29330596
TI  - Cognitive functioning: is it all or none?
AB  - Under various circumstances, the cognitive system operates in a global manner
      that is not very precise and barely discriminatory. This form of operating has
      been described via a general principal that Diamond (Developmental Psychology
      45:130-138, 2009) has denominated the All or None Hypothesis. This author has
      described a set of corollaries derived from this hypothesis that make it possible
      to verify it in each one of these domains. Although there is evidence of the
      global and non-discriminate way in which the cognitive system operates in
      populations of children, to date, there are no studies that have examined whether
      this mode of operation is also present in populations of adults. Researchers have
      yet to determine whether these corollaries apply to middle-aged adults. For this
      reason, this is the current study's principal objective. A sample of 73
      participants with ages ranging from 18 to 57 of both genders was evaluated. A
      modified version of the arrows test in Davidson et al. (Neuropsychologia 44:2037
      2078, 2006) was used to analyze the three corollaries. The results obtained in
      this study can be interpreted as evidence in favor of the corollaries analyzed
      herein. Furthermore, they indicate that adult populations have a global response
      mode that is barely differentiated and that is activated by default in the face
      of problems and situations that demand behaviors and/or thoughts that are not
      very analytical and differentiated. However, in contexts that demand greater
      discrimination, this global mode is substituted by a controlled mode that
      requires greater cognitive effort and more differentiated processing.

PMID- 29330597
TI  - Inpatient treatment of patients with idiopathic sudden sensorineural hearing
      loss: a population-based healthcare research study.
AB  - PURPOSE: The aim was to determine inpatient treatment rates of idiopathic sudden
      sensorineural hearing loss (ISSNHL) with focus on diagnostics, treatment, and
      outcome. METHODS: A retrospective population-based study in the federal state
      Thuringia in 2011 and 2012 was performed on all 490 inpatients (51% females,
      median age: 60 years) treated for ISSNHL (Median duration: 7 days). The
      association between analyzed parameters and the probability of recovery was
      tested using univariable and multivariable statistics. RESULTS: The inpatient
      treatment rate for ISSNHL was 11.23 per 100,000. 172 patients (35%) had an
      outpatient treatment prior to inpatient treatment. For pure-tone audiometry of
      the three most affected frequencies (3PTAmax), the initial median hearing loss
      was 66.67 dB, the median absolute hearing gain DeltaPTAabs was 10.0 dB, and the
      median relative hearing gain in relation with the contralateral side DeltaPTArel
      contral was 30.86%. 51% of the patients reached a DeltaPTAabs of >= 10 dB. About
      2 of 5 patients recovered to a DeltaPTArel contral >= 50% or reached <= 10 dB of
      contralateral ear. The multivariate analysis revealed that an ISSNHL on the left
      side [Hazard ratio (HR) = 1.6.88; confidence interval (CI) = 1.161-2.454], no
      down-sloping audiogram type (HR = 2.016; CI = 1.391-2.921), and no prior
      outpatient prednisolone treatment (HR = 2.374; CI = 1.505-3.745) were independent
      factors associated with better recovery (DeltaPTAabs >= 10 dB). CONCLUSION:
      Inpatient treatment of ISSNHL is variable in daily practice. The population-based
      recovery rate was worse than reported in clinical trials. More standardization
      and clearer criteria for outpatient, inpatient, and salvage therapy are needed.

PMID- 29330598
TI  - Satisfaction in rhinoplasty: the possible impact of anxiety and functional
      outcome.
AB  - BACKGROUND: Rhinoplasty is a complex but commonly applied surgical procedure.
      Patient satisfaction is the least discussed but one of the most important
      determinants of surgical success. OBJECTIVES: Evaluation of the patient
      satisfaction together with surgeon satisfaction were the main goals of this
      study. The roles of anxiety, gender, age and follow-up period were also studied.
      PATIENTS AND METHODS: 53 eligible patients operated by the first two authors
      within the previous 2 years were enrolled in the study. The medical records were
      reviewed for demographic data as well as the details of the surgical procedure.
      Functional and esthetic satisfactions of the patients were evaluated by VAS and
      ROE respectively. Surgeon satisfaction was evaluated by VAS in crosswise manner.
      Anxiety was measured by STAI_s and STAI_t scales. RESULTS: The analysis
      concerning esthetic results as well as functional results did not reveal any
      significant difference between the two surgeons (p = 0.132, p = 0.43
      respectively). ROE scores were significantly different among patients with "good"
      and "very good" functional results. The difference between surgeon satisfaction
      and patient satisfaction was found to be insignificant (p = 0.273). Correlation
      analysis yielded a positive correlation between STAI_I and STAI_II (Pearson r =
      0.335, p = 0.014) but not between STAI scores and ROE scores. Moreover, there was
      no relation between anxiety scores and the functional results. Likely, gender as
      well as age, follow-up, and surgical technique were not found to have any effect
      on patient satisfaction either. CONCLUSION: Patient satisfaction is preferential
      in rhinoplasty. In our patient series, patient satisfaction was shown to be
      correlated with functional outcome but not with surgeon satisfaction. Anxiety was
      not found to have a significant impact on results of rhinoplasty. Our results
      should be interpreted cautiously keeping in mind that our patients' primary drive
      for rhinoplasty was functional.

PMID- 29330599
TI  - Infraorbital foramen localization in orbitozygomatic fractures: a CT study with
      intraoperative finding.
AB  - OBJECTIVE: The aim of this study was to assess the infraorbital foramen (IOF)
      using CT in patients with Zygomaticomaxillary complex (ZMC) fractures (midface
      fracture). PATIENTS AND METHODS: This prospective study was carried out on 49
      patients had ZMC fractures (98 sides) and 27 patients (54 sides) with
      craniomaxillofacial fractures rather than fractured ZMC as a control. Using CT,
      position of IOF was documented on 3D view in relation to inferior orbital rim,
      tooth root relation and finally with a novel imaginary line passing between
      anterior nasal spine and whitnall tubercle. RESULTS: Position of IOF had fixed
      anatomical landmark: just lateral to a line drawn between the anterior nasal
      spine to whitnall tubercle (clinically between nasal tip-lateral canthal
      ligament) and lateral to vertical plane to root of maxillary canine also with
      variable distance from inferior orbital rim ranged from 4.56 to 18.03 mm with a
      mean of 7.9 +/- 2.447 mm. CONCLUSION: Even though ZMC fractures disturb the
      anatomical location of the ZMC bones, there are still preserved reliable fixed
      landmarks maxillofacial surgeons can depend on to identify and preserve ION.

PMID- 29330600
TI  - The impact of acoustic neuroma on long-term quality-of-life outcomes in the
      United Kingdom.
AB  - OBJECTIVE: To quantify the impact of acoustic neuroma on the quality-of-life
      (QOL) patients in the United Kingdom. STUDY DESIGN: Online questionnaire survey.
      PATIENTS: Members of the British Acoustic Neuroma Association received PANQOL
      questionnaires. RESULTS: Of the 880 BANA members contacted, 397 (45.1%)
      responded, although only 359 had complete datasets for analysis. Composite QOL
      scores were as follows: for microsurgery 58 (SD 35), for radiotherapy 56 (SD18),
      for combination of surgery and radiotherapy 49 (SD 14), and for the observation
      group 54 (SD 20). No statistical significance with ANOVA (p = 0.532). Mean (SD)
      composite QOL scores were as follows: for follow-up < 6 52 (SD 18), for follow-up
      6-10 55 (SD 20) and follow-up > 10 years 65 (SD 45). Overall, these values were
      significantly different compared by ANOVA (p < 0.001). Patients with facial
      paralysis showed no statistical significant differences between the different
      treatment groups. CONCLUSIONS: Short- (< 6 years) and long-term (> 10 years) QOL
      outcomes show no significant differences between the different treatment groups.

PMID- 29330602
TI  - Ecosystem carbon emissions from 2015 forest fires in interior Alaska.
AB  - BACKGROUND: In the summer of 2015, hundreds of wildfires burned across the state
      of Alaska, and consumed more than 1.6 million ha of boreal forest and wetlands in
      the Yukon-Koyukuk region. Mapping of 113 large wildfires using Landsat satellite
      images from before and after 2015 indicated that nearly 60% of this area was
      burned at moderate-to-high severity levels. Field measurements near the town of
      Tanana on the Yukon River were carried out in July of 2017 in both unburned and
      2015 burned forested areas (nearly adjacent to one-another) to visually verify
      locations of different Landsat burn severity classes (low, moderate, or high;
      LBS, MBS, HBS). RESULTS: Field measurements indicated that the loss of surface
      organic layers in boreal ecosystem fires is a major factor determining post-fire
      soil temperature changes, depth of thawing, and carbon losses from the mineral
      topsoil layer. Measurements in forest sites showed that soil temperature profiles
      to 30 cm depth at burned forest sites were higher by an average of 8-10  degrees
      C compared to unburned forest sites. Sampling and laboratory analysis indicated a
      65% reduction in soil carbon content and a 58% reduction in soil nitrogen content
      in severely burned sample sites compared to soil mineral samples from nearby
      unburned spruce forests. CONCLUSIONS: Combined with nearly unprecedented forest
      areas severely burned in the Interior region of Alaska in 2015, total ecosystem
      fire-related losses of carbon to the atmosphere exceeded most previous estimates
      for the state, owing mainly to inclusion of potential "mass wasting" and
      decomposition in the mineral soil carbon layer in the 2 years following these
      forest fires.

PMID- 29330601
TI  - Assessment of vestibular-evoked myogenic potentials and video head impulse test
      in type 2 diabetes mellitus patients with or without polyneuropathy.
AB  - This study aimed to compare cervical vestibular-evoked myogenic potentials
      (cVEMP), ocular vestibular-evoked myogenic potentials (oVEMP) and video head
      impulse test (vHIT) results between patients with type 2 diabetes mellitus (DM)
      or diabetic polyneuropathy (DPN) and healthy controls to determine vestibular end
      organ pathologies. The participants in the present study consisted of three
      groups: the type 2 DM group (n = 33 patients), the DPN group (n = 33 patients),
      and the age- and sex-matched control group (n = 35). Cervical VEMP, oVEMP and
      vHIT were performed for each participant in the study and test results were
      compared between the groups. Peak-to-peak amplitudes of cVEMP (p13-n21) and oVEMP
      (n10-p15) were significantly lower in the DM and DPN groups than the control
      group. The values of vHIT were not statistically different between the groups. To
      our knowledge, the present study is the first report investigating oVEMP and
      cVEMP responses combined with vHIT findings in patients with DM and DPN.
      Vestibular end-organ pathologies can be determined via clinical vestibular
      diagnostic tools in spite of prominent vestibular symptoms in patients with type
      2 DM as well as patients with DPN.

PMID- 29330603
TI  - Magnetic covalent triazine-based frameworks as magnetic solid-phase extraction
      adsorbents for sensitive determination of perfluorinated compounds in
      environmental water samples.
AB  - Covalent organic frameworks (COFs), which are a new type of carbonaceous
      polymeric material, have attracted great interest because of their large surface
      area and high chemical and thermal stability. However, to the best of our
      knowledge, no work has reported the use of magnetic COFs as adsorbents for
      magnetic solid-phase extraction (MSPE) to enrich and determine environmental
      pollutants. This work aims to investigate the feasibility of using covalent
      triazine-based framework (CTF)/Fe2O3 composites as MSPE adsorbents to enrich and
      analyze perfluorinated compounds (PFCs) at trace levels in water samples. Under
      the optimal conditions, the method developed exhibited low limits of detection
      (0.62-1.39 ng.L-1), a wide linear range (5-4000 ng L-1), good repeatability (1.12
      9.71%), and good reproducibility (2.45-7.74%). The new method was successfully
      used to determine PFCs in actual environmental water samples. MSPE based on
      CTF/Fe2O3 composites exhibits potential for analysis of PFCs at trace levels in
      environmental water samples. Graphical abstract Magnetic covalent triazine-based
      frameworks (CTFs) were used as magnetic solid-phase extraction adsorbents for the
      sensitive determination of perfluorinated compounds in environmental water
      samples. PFBA perfluorobutyric acid, PFBS perfluorobutane sulfonate, PFDA
      perfluorodecanoic acid, PFDoA perfluorododecanoic acid, PFHpA perfluoroheptanoic
      acid, PFHxA perfluorohexanoic acid, PFHxS perfluorohexane sulfonate, PFNA
      perfluorononanoic acid, PFOA perfluorooctanoic acid, PFPeA perfluoropentanoic
      acid, PFUdA Perfluoroundecanoic acid.

PMID- 29330605
TI  - Membrane-Ion Interactions.
AB  - Biomembranes assemble and operate at the interface with electrolyte solutions.
      Interactions between ions in solutions and the lipid affect the membrane
      structure, dynamics and electrostatic potential. In this article, I review some
      of the experimental and computational methods that are used to study membrane
      ions interactions. Experimental methods that account for membrane-ion
      interactions directly and indirectly are presented first. Then, studies in which
      molecular dynamics simulations were used to gain an understanding of membrane-ion
      interactions are surveyed. Finally, the current view on membrane-ion interactions
      and their significance is briefly discussed.

PMID- 29330604
TI  - Driving Forces of Translocation Through Bacterial Translocon SecYEG.
AB  - This review focusses on the energetics of protein translocation via the Sec
      translocation machinery. First we complement structural data about SecYEG's
      conformational rearrangements by insight obtained from functional assays. These
      include measurements of SecYEG permeability that allow assessment of channel
      gating by ligand binding and membrane voltage. Second we will discuss the power
      stroke and Brownian ratcheting models of substrate translocation and the role
      that the two models assign to the putative driving forces: (i) ATP (SecA) and GTP
      (ribosome) hydrolysis, (ii) interaction with accessory proteins, (iii) membrane
      partitioning and folding, (iv) proton motive force (PMF), and (v) entropic
      contributions. Our analysis underlines how important energized membranes are for
      unravelling the translocation mechanism in future experiments.

PMID- 29330606
TI  - The associations of poor psychiatric well-being among incarcerated men with
      injecting drug use histories in Victoria, Australia.
AB  - BACKGROUND: Dual substance dependence and psychiatric and psychological
      morbidities are overrepresented in prison populations and associated with
      reoffending. In the context of an increasing prison population in Australia,
      investigating the needs of vulnerable people in prison with a dual diagnosis can
      help inform in-prison screening and treatment and improve prison and community
      service integration and continuation of care. In this study we quantified
      psychiatric well-being in a sample of people in prison with a history of
      injecting drug use in Victoria, Australia, and identified factors associated with
      this outcome. METHODS AND RESULTS: Data for this paper come from baseline
      interviews undertaken in the weeks prior to release as part of a prospective
      cohort study of incarcerated men who reported regular injecting drug use prior to
      their current sentence. Eligible participants completed a researcher-administered
      structured questionnaire that canvassed a range of issues. Psychiatric well-being
      was assessed using the 12-item General Health Questionnaire (GHQ-12) and
      potential correlates were included based on a review of the literature. Of the
      317 men included for analyses, 139 were classified as experiencing current poor
      psychiatric well-being. In the multivariate model using modified logistic
      regression, history of suicide attempt (aOR = 1.36, 95%CI 1.03-1.78), two or more
      medical conditions (aOR = 1.87, 95%CI 1.30-2.67) and use of crystal
      methamphetamine in the week prior to their current sentence (aOR = 1.52, 95%CI
      1.05-2.22) were statistically significantly associated with current poor
      psychiatric well-being. CONCLUSIONS: Comprehensively addressing the health
      related needs for this vulnerable population will require a multidisciplinary
      approach and enhancing opportunities to screen and triage people in prison for
      mental health and other potential co-occurring health issues will provide
      opportunities to better address individual health needs and reoffending risk.

PMID- 29330607
TI  - River Continuity Restoration and Diadromous Fishes: Much More than an Ecological
      Issue.
AB  - Ecosystem fragmentation is a serious threat to biodiversity and one of the main
      challenges in ecosystem restoration. River continuity restoration (RCR) has often
      targeted diadromous fishes, a group of species supporting strong cultural and
      economic values and especially sensitive to river fragmentation. Yet it has
      frequently produced mixed results and diadromous fishes remain at very low levels
      of abundance. Against this background, this paper presents the main challenges
      for defining, evaluating and achieving effective RCR. We first identify
      challenges specific to disciplines. In ecology, there is a need to develop
      quantitative and mechanistic models to support decision making, accounting for
      both direct and indirect impacts of river obstacles and working at the river
      catchment scale. In a context of dwindling abundances and reduced market value,
      cultural services provided by diadromous fishes are becoming increasingly
      prominent. Methods for carrying out economic quantification of non-market values
      of diadromous fishes become ever more urgent. Given current challenges for rivers
      to meet all needs sustainably, conflicts arise over the legitimate use of water
      resources for human purposes. Concepts and methods from political science and
      geography are needed to develop understandings on how the political work of
      public authorities and stakeholders can influence the legitimacy of restoration
      projects. Finally, the most exciting challenge is to combine disciplinary
      outcomes to achieve a multidisciplinary approach to RCR. Accordingly, the co
      construction of intermediary objects and diagrams of flows of knowledge among
      disciplines can be first steps towards new frameworks supporting restoration
      design and planning.

PMID- 29330608
TI  - Environmental Performance Information Use by Conservation Agency Staff.
AB  - Performance-based conservation has long been recognized as crucial to improving
      program effectiveness, particularly when environmental conditions are dynamic.
      Yet few studies have investigated the use of environmental performance
      information by staff of conservation organizations. This article identifies
      attitudinal, policy and organizational factors influencing the use of a type of
      performance information-water quality information-by Soil and Water Conservation
      District staff in the Upper Mississippi River Basin region. An online survey (n =
      277) revealed a number of important variables associated with greater information
      use. Variables included employees' prosocial motivation, or the belief that they
      helped people and natural resources through their job, the perceived
      trustworthiness of data, the presence of a U.S. Clean Water Act Total Maximum
      Daily Load standard designation, and staff discretion to prioritize programs
      locally. Conservation programs that retain motivated staff and provide them the
      resources and flexibility to plan and evaluate their work with environmental data
      may increase conservation effectiveness under changing conditions.

PMID- 29330609
TI  - Determination of Appropriate Service Delivery Level for Quantitative Attributes
      of Household Toilets in Rural Settlements of India from Users' Perspective.
AB  - Improvement of quality of sanitation services in rural settlements is an
      important development goal in developing countries including India and
      accordingly several strategies are adopted which promote the demand and use of
      household toilets through creating awareness and providing subsidies to poor
      people for construction of household toilets with service-level standards
      specified from experts' perspective. In many cases, users are unsatisfied with
      the quality of toilets constructed using subsidies and the same remain unused.
      Users' satisfaction depends on their perceptions of service quality of individual
      attributes and overall service quality of the household toilets, which is an
      important determinant of sustainability and sustained use of toilets. This study
      aims to assess and benchmark the appropriate service delivery level for
      quantitative attributes of rural household toilets based on user perception. The
      service quality is determined with the help of level of service (LOS) scales
      developed using successive interval scaling technique, the zone of tolerance
      (ZOT), and users satisfaction level (USL) which relates service delivery levels
      with user satisfaction directly. The study finds that the service quality of most
      of the attributes of household toilets constructed using subsidies is perceived
      as poor. The results also suggest that most of the users expect to have a toilet
      with the service level of attributes ranging between LOS A and LOS B.

PMID- 29330610
TI  - Nutrition delivery of a model-based ICU glycaemic control system.
AB  - BACKGROUND: Hyperglycaemia is commonplace in the adult intensive care unit (ICU),
      associated with increased morbidity and mortality. Effective glycaemic control
      (GC) can reduce morbidity and mortality, but has proven difficult. STAR is a
      proven, effective model-based ICU GC protocol that uniquely maintains normo
      glycaemia by changing both insulin and nutrition interventions to maximise
      nutrition in the context of GC in the 4.4-8.0 mmol/L range. Hence, the level of
      nutrition it provides is a time-varying estimate of the patient-specific ability
      to take up glucose. METHODS: First, the clinical provision of nutrition by STAR
      in Christchurch Hospital, New Zealand (N = 221 Patients) is evaluated versus
      other ICUs, based on the Cahill et al. survey of 158 ICUs. Second, the inter- and
      intra- patient variation of nutrition delivery with STAR is analysed. Nutrition
      rates are in terms of percentage of caloric goal achieved. RESULTS: Mean
      nutrition rates clinically achieved by STAR were significantly higher than the
      mean and best ICU surveyed, for the first 3 days of ICU stay. There was large
      inter-patient variation in nutrition rates achieved per day, which reduced
      overtime as patient-specific metabolic state stabilised. Median intra-patient
      variation was 12.9%; however, the interquartile range of the mean per-patient
      nutrition rates achieved was 74.3-98.2%, suggesting patients do not deviate much
      from their mean patient-specific nutrition rate. Thus, the ability to tolerate
      glucose intake varies significantly between, rather than within, patients.
      CONCLUSIONS: Overall, STAR's protocol-driven changes in nutrition rate provide
      higher nutrition rates to hyperglycaemic patients than those of 158 ICUs from 20
      countries. There is significant inter-patient variability between patients to
      tolerate and uptake glucose, where intra-patient variability over stay is much
      lower. Thus, a best nutrition rate is likely patient specific for patients
      requiring GC. More importantly, these overall outcomes show high nutrition
      delivery and safe, effective GC are not exclusive and that restricting nutrition
      for GC does not limit overall nutritional intake compared to other ICUs.

PMID- 29330611
TI  - A comparison of different sealants preventing demineralization around brackets.
AB  - AIM: Aim of the study was to compare how six different sealants resisted thermal,
      mechanical, and chemical loading in vitro. MATERIALS AND METHODS: In all, 120
      extracted human, nondecayed molars were divided into six groups (20 samples each)
      and embedded in resin blocks. The buccal surfaces of the tooth samples were
      polished and divided into three areas. Area A contained the product to be
      analyzed, area B was covered with colorless nail varnish (negative control), and
      area C remained untreated (positive control). The samples were stored in 0.1%
      thymol solution. To simulate a 3-month thermomechanical load, the samples were
      subjected to thermal cycling and a cleaning device. After 7 days incubation in a
      ten Cate demineralization solution (pH value: 4.6), the samples were dissected
      using a band saw and the lesion depths and demineralization areas were evaluated
      and compared microscopically. RESULTS: The tooth surfaces treated with PRO
      SEAL(r) showed no demineralization. Mean lesion depths of 108.1, 119.9, 154.9,
      149.2, and 184.5 MUm were found with Alpha-Glaze(r), Seal&Protect(r),
      Tiefenfluorid(r), Protecto(r), and Fluor Protector, respectively. There was a
      significant difference between PRO SEAL(r) and the other products (p > 0.0001).
      There was no significant difference between the other products. CONCLUSION: PRO
      SEAL(r) resisted thermal, mechanical, and chemical loading in vitro, providing
      protection against white spot lesions.

PMID- 29330613
TI  - [Bone replacement materials and antibiotics in revision surgery].

PMID- 29330612
TI  - Analysis of the stomatognathic system of children according orthodontic treatment
      needs.
AB  - PURPOSE: The present study evaluated electromyographic activity (EMG),
      masticatory performance, and tongue strength in children without and with
      orthodontic treatment needs. PATIENTS AND METHODS: A total of 90 children were
      screened and divided into the following groups: Group I (no treatment needed;
      mean age: 8.00 +/- 0.43 years; n = 26), Group II (few malocclusions, treatment
      needed; mean age: 8.89 +/- 0.43 years; n = 28), and Group III (slight-to
      borderline treatment needed; mean age: 8.44 +/- 0.22 years; n = 36). Orthodontic
      treatment need was classified on the basis of IOTN-DHC (Index of Orthodontic
      Treatment Need - Dental Health Component). The electromyographic Trigno EMG
      Systems was used for muscle analysis and the Iowa Oral Pressure Instrument (IOPI)
      was used to measure tongue strength. Data were analyzed using normality tests and
      one-way analysis of variance with a Bonferroni post hoc test (p <= 0.05).
      RESULTS: EMG in almost all mandibular movements was higher in Group III with
      statistically significant differences compared to position at rest: right
      masseter (p = 0.03); protrusion: left temporal (p = 0.02); saliva swallowing:
      left temporal (p = 0.05) and water swallowing: orbicularis oris mouth, right
      upper segment (p = 0.05). Lower masticatory performance was found in Group III,
      but the difference compared to Group I and II was not significant. There were no
      significant differences between the groups in terms of tongue strength.
      CONCLUSIONS: Children with borderline orthodontic treatment needs show functional
      disorders of the stomatognathic system.

PMID- 29330615
TI  - The parameter identification problem for SIR epidemic models: identifying
      unreported cases.
AB  - A SIR epidemic model is analyzed with respect to identification of its
      parameters, based upon reported case data from public health sources. The
      objective of the analysis is to understand the relation of unreported cases to
      reported cases. In many epidemic diseases the ratio of unreported to reported
      cases is very high, and of major importance in implementing measures for
      controlling the epidemic. This ratio can be estimated by the identification of
      parameters for the model from reported case data. The analysis is applied to
      three examples: (1) the Hong Kong seasonal influenza epidemic in New York City in
      1968-1969, (2) the bubonic plague epidemic in Bombay, India in 1906, and (3) the
      seasonal influenza epidemic in Puerto Rico in 2016-2017.

PMID- 29330616
TI  - [Magnetic resonance cisternography].
AB  - CLINICAL/METHODICAL ISSUE: Conventional MRI can be insufficient to depict certain
      pathologies of the cerebrospinal fluid (CSF)-filled spaces. STANDARD RADIOLOGICAL
      METHODS: 3-D T2-weighted sequences and phase-contrast imaging have a high
      sensitivity for pathologies of the CSF-filled spaces, but are susceptible to
      artifacts in some cases. METHODICAL INNOVATIONS/PERFORMANCE: Magnetic resonance
      (MR) cisternography directly depicts the connection between CSF-filled spaces.

PMID- 29330614
TI  - Effect of ancymidol on cell wall metabolism in growing maize cells.
AB  - MAIN CONCLUSION: Ancymidol inhibits the incorporation of cellulose into cell
      walls of maize cell cultures in a gibberellin-independent manner, impairing cell
      growth; the reduction in the cellulose content is compensated with xylans.
      Ancymidol is a plant growth retardant which impairs gibberellin biosynthesis. It
      has been reported to inhibit cellulose synthesis by tobacco cells, based on its
      cell-malforming effects. To ascertain the putative role of ancymidol as a
      cellulose biosynthesis inhibitor, we conducted a biochemical study of its effect
      on cell growth and cell wall metabolism in maize cultured cells. Ancymidol
      concentrations <= 500 uM progressively reduced cell growth and induced globular
      cell shape without affecting cell viability. However, cell growth and viability
      were strongly reduced by ancymidol concentrations >= 1.5 mM. The I50 value for
      the effect of ancymidol on FW gain was 658 uM. A reversal of the inhibitory
      effects on cell growth was observed when 500 uM ancymidol-treated cultures were
      supplemented with 100 uM GA3. Ancymidol impaired the accumulation of cellulose in
      cell walls, as monitored by FTIR spectroscopy. Cells treated with 500 uM
      ancymidol showed a ~ 60% reduction in cellulose content, with no further change
      as the ancymidol concentration increased. Cellulose content was partially
      restored by 100 uM GA3. Radiolabeling experiments confirmed that ancymidol
      reduced the incorporation of [14C]glucose into alpha-cellulose and this reduction
      was not reverted by the simultaneous application of GA3. RT-PCR analysis
      indicated that the cellulose biosynthesis inhibition caused by ancymidol is not
      related to a downregulation of ZmCesA gene expression. Additionally, ancymidol
      treatment increased the incorporation of [3H]arabinose into a hemicellulose
      enriched fraction, and up-regulated ZmIRX9 and ZmIRX10L gene expression,
      indicating an enhancement in the biosynthesis of arabinoxylans as a compensatory
      response to cellulose reduction.

PMID- 29330617
TI  - Characterizing genomic differences of human cancer stratified by the TP53
      mutation status.
AB  - The key roles of the TP53 mutation in cancer have been well established. TP53 is
      the most frequently mutated gene, and its inactivation is widespread among human
      cancer types. However, the landscape of genomic alterations in human cancers
      stratified by the TP53 mutation has not yet been described. We obtained somatic
      mutation and copy number change data of 6551 regular-mutated samples from the
      Cancer Genome Atlas (TCGA) and compared significantly mutated genes (SMGs), copy
      number alterations, mutational signatures and mutational strand asymmetries
      between cancer samples with and without the TP53 mutation. We identified 126
      SMGs, 30 of which were statistically significant in both the TP53 mutant and wild
      type groups. Several SMGs, such as VHL, SMAD4 and PTEN, showed a mutation bias
      towards the TP53 wild-type group, whereas ATRX, IDH1 and RB1 were more prevalent
      in the TP53 mutant group. Five mutational signatures were extracted from the
      combined TCGA dataset on which mutational asymmetry analysis was performed,
      revealing that the TP53 mutant group exhibited substantially greater replication
      and transcription biases. Furthermore, we found that alterations of multiple
      genes in a merged mutually exclusive network composed of BRAF, EGFR, PAK1,
      PIK3CA, PTEN, APC and TERT were related to shortened survival in the TP53 wild
      type group. In summary, we characterized the genomic differences and similarities
      underlying human cancers stratified by the TP53 mutation and identified multi
      gene alterations of a merged mutually exclusive network to be a poor prognostic
      factor for the TP53 wild-type group.

PMID- 29330618
TI  - Oleic acid chlorohydrin, a new early biomarker for the prediction of acute
      pancreatitis severity in humans.
AB  - BACKGROUND: The early prediction of the severity of acute pancreatitis still
      represents a challenge for clinicians. Experimental studies have revealed the
      generation of specific halogenated lipids, in particular oleic acid chlorohydrin,
      in the early stages of acute pancreatitis. We hypothesized that the levels of
      circulating oleic acid chlorohydrin might be a useful early prognostic biomarker
      in acute pancreatitis in humans. METHODS: In a prospective, multicenter cohort
      study, plasma samples collected within 24 h after presentation in the emergency
      room from 59 patients with acute pancreatitis and from 9 healthy subjects were
      assessed for oleic acid chlorohydrin levels. RESULTS: Pancreatitis was mild in 30
      patients, moderately severe in 16 and severe in 13. Oleic acid chlorohydrin
      levels within 24 h after presentation were significantly higher in patients that
      later progressed to moderate and severe acute pancreatitis. Using 7.49 nM as the
      cutoff point, oleic acid chlorohydrin distinguished mild from moderately severe
      to-severe pancreatitis with high sensitivity/specificity (96.6/90.0%) and
      positive/negative predictive values (90.3/96.4%). Using 32.40 nM as the cutoff
      value sensitivity, specificity, positive and negative predictive values were all
      100% for severe acute pancreatitis. It was found to be a better prognostic marker
      than BISAP score, hematocrit at 48 h, SIRS at admission, persistent SIRS or C
      reactive protein at 48 h. CONCLUSIONS: Oleic acid chlorohydrin concentration in
      plasma is elevated in patients with acute pancreatitis on admission and
      correlates with a high degree with the final severity of the disease, indicating
      that it has potential to serve as an early prognostic marker for acute
      pancreatitis severity.

PMID- 29330619
TI  - MR arthrography of the hip: diagnostic performance and image quality of 3D-steady
      state free precession versus 2D turbo spin echo sequences.
AB  - OBJECTIVE: To retrospectively compare the diagnostic performance of isotropic 3D
      steady-state free precession (3D-SSFP) sequences with 2D turbo spin-echo proton
      density-weighted fat-saturated (2D-TSE-PD fs) images in hip magnetic resonance
      arthrography; arthroscopy was a standard of reference. METHODS: Eighty-one
      patients with suspected labral tears who underwent hip MR arthrography (3-T
      scanner) were included. 2D-TSE-PD fs sequences were acquired in three planes and
      a singular sagittal 3D-SSFP. Labral tears, cartilage pathology and bone marrow
      were independently assessed by two blinded radiologists using a 5-point Likert
      scale. Accuracy was determined in 39 patients using invasive arthroscopy.
      RESULTS: Diagnostic confidence of labral and cartilaginous pathologies based on
      image quality was rated higher for 3D-SSFP (4.5 +/- 0.8; 4.35 +/- 0.7; p <
      0.0001), but inferior for bone marrow pathology (3.9 +/- 0.7; 4.0 +/- 0.7; p <
      0.0001). In the arthroscopy patients, similar sensitivity (85.9%) but higher
      specificity (74.4vs.42.9%) and higher positive and negative predictive values
      were found in 3D-SSFP of labral and cartilage pathologies. CONCLUSIONS: 3D-SSFP
      in hip magnetic resonance arthrography offers increased accuracy in detecting
      labral and cartilage pathologies compared with 2D-TSE-PD, while reducing the
      acquisition time. A drawback of 3D-SSFP was the inferior diagnostic confidence
      for bone marrow evaluation; thus, 3D-SSFP should be combined with conventional 2D
      TSE sequences.

PMID- 29330621
TI  - Nonuniversal behaviour of helical two-dimensional three-component turbulence.
AB  - The dynamics of two-dimensional three-component (2D3C) flows is relevant to
      describe the long-time evolution of strongly rotating flows and/or of conducting
      fluids with a strong mean magnetic field. We show that in the presence of a
      strong helical forcing, the out-of-plane component ceases to behave as a passive
      advected quantity and develops a nontrivial dynamics which deeply changes its
      large-scale properties. We show that a small-scale helicity injection correlates
      the input on the 2D component with the one on the out-of-plane component. As a
      result, the third component develops a nontrivial energy transfer. The latter is
      mediated by homochiral triads, confirming the strong 3D nature of the leading
      dynamical interactions. In conclusion, we show that the out-of-plane component in
      a 2D3C flow enjoys strong nonuniversal properties as a function of the degree of
      mirror symmetry of the small-scale forcing.

PMID- 29330620
TI  - Impact of sirtuin-1 expression on H3K56 acetylation and oxidative stress: a
      double-blind randomized controlled trial with resveratrol supplementation.
AB  - AIMS: Sirtuin-1 (SIRT-1) down-regulation in type 2 diabetes mellitus (T2DM) has
      been associated with epigenetic markers of oxidative stress. We herein aim to
      evaluate whether an increase in SIRT-1 expression affects histone 3 acetylation
      at the 56 lysine residue (H3K56ac) in T2DM patients randomly selected to receive
      either resveratrol (40 mg or 500 mg) or a placebo for 6 months. The primary
      outcome is changes in the H3K56ac level by variation in SIRT-1 expression and the
      secondary outcome is the evidence of association between SIRT-1 level,
      antioxidant markers (TAS), and metabolic variables. METHODS AND RESULTS: At
      baseline, peripheral blood mononuclear cell H3K56ac values among the SIRT-1
      tertiles did not differ. At trial end, SIRT-1 levels were significantly higher in
      patients receiving 500 mg resveratrol. At follow-up, patients were divided into
      tertiles of delta (trial end minus baseline) SIRT-1 value. Significant reductions
      in H3K56ac and body fat percentage were found in the highest tertile as were
      increased TAS levels. A multiple logistic regression model showed that the
      highest delta SIRT-1 tertile was inversely associated with variations in H3K56ac
      (OR = 0.66; 95% CI 0.44-0.99), TAS (OR = 1.01; 95% CI 1.00-1.02), and body fat
      percentage (OR = 0.75; 95% CI 0.58-0.96). CONCLUSIONS: We provide new knowledge
      on H3K56ac and SIRT-1 association in T2DM. These data suggest that boosting SIRT
      1 expression/activation may impact redox homeostasis in these patients.
      ClinicalTrials.gov Identifier NCT02244879.

PMID- 29330622
TI  - Association of soil potassium and sodium concentrations with spatial disparities
      of prevalence and mortality rates of hypertensive diseases in the USA.
AB  - Crop available soil potassium is generally low and on the decline in the
      southeastern states of the USA because of the increasing crop and runoff removal
      and decreasing application of potassium fertilizer. Hypertension-related
      mortality rates are also high in the southeastern states and are on the rise.
      Among 41 elements analyzed from 4856 sites across all 48 states, potassium is
      identified as the only independent element whose soil concentration has
      significant association with spatial disparities of essential hypertension and
      hypertension-related mortality rates in the 48 states between 1999 and 2014.
      Essential hypertension and hypertension-related mortality rates of the 6 states
      with the lowest soil potassium concentration are about 50-26% higher than that of
      the 6 states with the highest soil potassium concentration in the 48 states (RR:
      1.50, 1.26, low CI 95% 1.47, 1.25 and upper CI 95% 1.53, 1.27, respectively).
      Though sodium was not identified as an independent factor, an apparent
      significant inverse correlation exists between hypertension prevalence rates and
      soil sodium concentration in the 48 states (r = - 0.66, p = 0.00). There likely
      has been a decline of potassium in USA produces per unit weight over time and a
      likely association between this decline and increasing hypertension rate,
      particularly in the southeastern states. Hence, results of this study suggest the
      need of increasing potassium intakes for reducing hypertension-related mortality
      rates in the southeastern states. Results of this study also support further
      examination of potential benefits of sodium from mixture of non-chloride salts in
      natural produces.

PMID- 29330623
TI  - Comment on a meta-analysis evaluating the cardiac toxicity of lapatinib in
      patients with breast cancer and other HER2-positive cancers.

PMID- 29330624
TI  - Functional transcriptomic annotation and protein-protein interaction network
      analysis identify NEK2, BIRC5, and TOP2A as potential targets in obese patients
      with luminal A breast cancer.
AB  - PURPOSE: Although obesity is a risk factor for breast cancer, little effort has
      been made in the identification of druggable molecular alterations in obese
      breast cancer patients. Tumors are controlled by their surrounding
      microenvironment, in which the adipose tissue is a main component. In this work,
      we intended to describe molecular alterations at a transcriptomic and protein
      protein interaction (PPI) level between obese and non-obese patients. METHODS AND
      RESULTS: Gene expression data of 269 primary breast tumors were compared between
      normal-weight (BMI < 25, n = 130) and obese (IMC > 30, n = 139) patients. No
      significant differences were found for the global breast cancer population.
      However, within the luminal A subtype, upregulation of 81 genes was observed in
      the obese group (FC >= 1.4). Next, we explored the association of these genes
      with patient outcome, observing that 39 were linked with detrimental outcome.
      Their PPI map formed highly compact cluster and functional annotation analyses
      showed that cell cycle, cell proliferation, cell differentiation, and cellular
      response to extracellular stimuli were the more altered functions. Combined
      analyses of genes within the described functions are correlated with poor
      outcome. PPI network analyses for each function were to search for druggable
      opportunities. We identified 16 potentially druggable candidates. Among them,
      NEK2, BIRC5, and TOP2A were also found to be amplified in breast cancer,
      suggesting that they could act as strategic players in the obese-deregulated
      transcriptome. CONCLUSION: In summary, our in silico analysis describes molecular
      alterations of luminal A tumors and proposes a druggable PPI network in obese
      patients with potential for translation to the clinical practice.

PMID- 29330625
TI  - Facilitating adherence to endocrine therapy in breast cancer: stability and
      predictive power of treatment expectations in a 2-year prospective study.
AB  - PURPOSE: To identify modifiable factors predictive of long-term adherence to
      adjuvant endocrine therapy (AET). METHODS: As part of a 2-year cohort study in
      primary care (n = 116), we investigated whether initial treatment expectations
      predict adherence at 24 months after controlling for demographic, medical, and
      psychosocial variables. Treatment expectations were measured as necessity-concern
      beliefs, expected side-effect severity, and expected coping with side effects.
      Their stability over time and differences of trajectories between the adherent
      and nonadherent group were examined. RESULTS: Nonadherence at 24 months was 14.7%
      (n = 17). Side-effect severity at 3 months [OR 0.25, 95% CI (0.08, 0.81), p =
      0.02] and necessity-concern beliefs [OR 2.03, 95% CI (1.11, 3.72), p = 0.02] were
      the sole predictors of adherence. Necessity-concern beliefs remained stable over
      2 years, whereas expected side-effect severity (p = 0.01, eta p2  = 0.07) and
      expected coping with side effects became less optimistic over time (p < 0.001,
      eta p2  = 0.19), the latter particularly among nonadherers (p < 0.01, eta p2  =
      0.10). CONCLUSIONS: Patients' initial necessity-concern beliefs about the AET and
      early severity of side effects affect long-term adherence. Expecting poor
      management of side effects may also facilitate nonadherence. We suggest that
      discussing benefits, addressing concerns of AET, and providing side-effect coping
      strategies could constitute a feasible and promising option to improve adherence
      in clinical practice.

PMID- 29330626
TI  - Low-frequency rTMS in the superior parietal cortex affects the working memory in
      horizontal axis during the spatial task performance.
AB  - Spatial working memory has been extensively investigated with different tasks,
      treatments, and analysis tools. Several studies suggest that low frequency of the
      repetitive transcranial magnetic stimulation (rTMS) applied to the parietal
      cortex may influence spatial working memory (SWM). However, it is not yet known
      if after low-frequency rTMS applied to the superior parietal cortex, according to
      Pz electroencephalography (EEG) electrode, would change the orientation
      interpretation about the vertical and horizontal axes coordinates in an SWM task.
      The current study aims at filling this gap and obtains a better understanding of
      the low-frequency rTMS effect in SWM. In this crossover study, we select 20
      healthy subjects in two conditions (control and 1-Hz rTMS). The subjects
      performed an SWM task with two random coordinates. Our results presented that low
      frequency rTMS applied over the superior parietal cortex may influence the SWM to
      lead to a larger distance of axes interception point (p < 0.05). We conclude that
      low-frequency rTMS over the superior parietal cortex (SPC) changes the SWM
      performance, and it has more predominance in horizontal axis.

PMID- 29330628
TI  - Clinical and CN-SFEMG evaluation of neostigmine test in myasthenia gravis.
AB  - Neostigmine test (NT) is a pharmacological test, demonstrating a clinical
      improvement in patients affected by myasthenia gravis (MG). We aim to compare
      clinical evaluation and neurophysiological recordings by concentric-needle single
      fiber electromyography (CN-SFEMG) in response to acute administration of
      neostigmine in ocular and generalized MG patients. Twenty-three MG patients (10
      with ocular MG and 13 with generalized MG) were evaluated before and after 90 min
      neostigmine 0.5-mg administration. Clinical responsiveness was assessed by MG
      composite (MGC) scale. Neurophysiological evaluation by CN-SFEMG considered
      analysis of mean value of consecutive differences (MCD), single-pair jitter, and
      blocks. MGC scores significantly improved after NT in generalized MG patients
      (MGC 11.1 +/- 7.6 vs 9.1 +/- 6.7, p = 0.02), whereas the improvement was not
      significant in the ocular group. CN-SFEMG recordings significantly improved after
      NT in generalized MG patients (MCD 58.9 +/- 18.8 vs 45.9 +/- 23.2 MUs, p = 0.003;
      single-pair jitter 49.8 +/- 26.9 vs 24.1 +/- 26.7%, p = 0.0001; blocks 6.2 +/-
      9.5 vs 2.6 +/- 7.4%, p = 0.03) as well as in ocular MG patients (MCD 50.8 +/-
      22.7 vs 40.1 +/- 22.9 MUs, p = 0.01; single-pair jitter 35.9 +/- 23.7 vs 20.0 +/-
      25.1%, p = 0.001). CN-SFEMG is a reliable tool to evaluate responsiveness to
      acute administration of neostigmine in MG. Moreover, neurophysiological
      modifications to NT could show subclinical improvement in ocular MG better than
      that of the clinical scale.

PMID- 29330629
TI  - Giant left atrial myxoma causing acute ischemic stroke in a child.
AB  - Ischemic stroke is uncommon in pediatric populations and is sometimes caused by
      cardiac myxoma. In such cases, neurological deficits initially present in
      ischemic stroke due to emboli or thrombi of the myxoma. Echocardiography is
      helpful to diagnose myxoma in a timely manner and allows urgent surgical
      resection of the myxoma. We report a successful case of myxoma in a 7-year-old
      boy who initially presented with left-sided hemiparesis.

PMID- 29330630
TI  - Evaluation of pain during high-intensity focused ultrasound ablation of benign
      thyroid nodules.
AB  - OBJECTIVE: To assess severity and factors of pain during high-intensity focused
      ultrasound (HIFU) ablation of benign thyroid nodules. METHODS: 128 patients who
      underwent a HIFU ablation for a benign thyroid nodule were analysed. All patients
      received a bolus of intravenous pethidine and diazepam before treatment. After
      treatment, patients were asked to rate their overall pain experience on a visual
      analogue scale (0-100) (0 = no pain; 100 = worse possible pain) during treatment,
      2 h after treatment and the following morning. Binary logistic regression was
      performed to evaluate associated factors for pain including patient demographics,
      nodule size, body mass index (BMI) and treatment parameters. RESULTS: At T1,
      median (range) pain score was 65.0 (0.00-100.00). Only 16 (12.5 %) patients had a
      pain score of zero. In multivariate analysis, only lower BMI (OR 1.265, 95 % CI
      1.102-1.452, p=0.001) and longer nodule diameter (OR 1.462, 95 % CI 1.071-1.996,
      p=0.017) were independent factors for pain score at T1 <= 65.0. CONCLUSIONS: A
      moderate to severe amount of pain was reported during ablation of benign thyroid
      nodules in over 50 % of patients. Patients' BMI and length of nodule diameter
      were independent variables for pain during HIFU ablation. KEY POINTS: * Pain was
      moderate to severe during HIFU ablation of thyroid nodules. * Only one in eight
      patients reported no pain during ablation. * Level of energy per pulse did not
      affect pain. * Patients with lower BMI and larger nodules had less pain.

PMID- 29330632
TI  - Inate immunity in rosacea. Langerhans cells, plasmacytoid dentritic cells, Toll
      like receptors and inducible oxide nitric synthase (iNOS) expression in skin
      specimens: case-control study.
AB  - Rosacea is a chronic inflammatory condition with predominant facial involvement.
      Because of that, many patients sense that rosacea affects quality of life. The
      etiology of rosacea remains unknown. Recent studies have suggested that aberrant
      innate immunity is central to this disease. The aim of this study was to examine
      the presence of Langerhans cells, plasmacytoid dentritic cells (PDC), the
      expression of Toll-like receptors (TLR) and inducible oxide nitric synthase
      (iNOS) in skin of patients with rosacea, to highlight the participation of innate
      immunity in its pathogenesis. 28 biopsy specimens were taken from patients with
      clinical and histopathological findings of rosacea. Immunohistochemical
      demonstration of Langerhans cells (anti-CD1a antibody), PDC (anti-CD 123
      antibody), TLR2, TLR4 and iNOS was performed in skin samples and compared with
      normal skin controls. The expression of Langerhans cells was lower in rosacea
      group than in control group. PDC were found in skin samples of rosacea as
      isolated cells and forming small clusters. Expression of TLR2, TLR4 and iNOS was
      higher in rosacea samples than in normal skin controls. This research
      demonstrates early and late stage components of innate immunity in specimens of
      rosacea ratifying the existence of an altered innate immunity in its
      pathogenesis.

PMID- 29330631
TI  - Apparent diffusion coefficient mapping using diffusion-weighted MRI: impact of
      background parenchymal enhancement, amount of fibroglandular tissue and
      menopausal status on breast cancer diagnosis.
AB  - OBJECTIVES: To investigate the impact of background parenchymal enhancement
      (BPE), amount of fibroglandular tissue (FGT) and menopausal status on apparent
      diffusion coefficient (ADC) values in differentiation between malignant and
      benign lesions. METHODS: In this HIPAA-compliant study, mean ADC values of 218
      malignant and 130 benign lesions from 288 patients were retrospectively
      evaluated. The differences in mean ADC values between benign and malignant
      lesions were calculated within groups stratified by BPE level (high/low), amount
      of FGT (dense/non-dense) and menopausal status (premenopausal/postmenopausal).
      Sensitivities and specificities for distinguishing malignant from benign lesions
      within different groups were compared for statistical significance. RESULTS: The
      mean ADC value for malignant lesions was significantly lower compared to that for
      benign lesions (1.07+/-0.21 x 10-3 mm2/s vs. 1.53+/-0.26 x 10-3 mm2/s)
      (p<0.0001). Using the optimal cut-off point of 1.30 x 10-3 mm2/s, an area under
      the curve of 0.918 was obtained, with sensitivity and specificity both of 87 %.
      There was no statistically significant difference in sensitivities and
      specificities of ADC values between different groups stratified by BPE level,
      amount of FGT or menopausal status. CONCLUSIONS: Differentiation between benign
      and malignant lesions on ADC values is not significantly affected by BPE level,
      amount of FGT or menopausal status. KEY POINTS: * ADC allows differentiation
      between benign and malignant lesions. * ADC is useful for breast cancer diagnosis
      despite different patient characteristics. * BPE, FGT or menopause do not
      significantly affect sensitivity and specificity.

PMID- 29330633
TI  - A seven-center examination of the relationship between monthly volume and
      mortality in trauma: a hypothesis-generating study.
AB  - INTRODUCTION: The relationship between trauma volumes and patient outcomes
      continues to be controversial, with limited data available regarding the effect
      of month-to-month trauma volume variability on clinical results. This study
      examines the relationship between monthly trauma volume variations and patient
      mortality at seven Level I Trauma Centers located in the Eastern United States.
      We hypothesized that higher monthly trauma volumes may be associated with lower
      corresponding mortality. METHODS: Monthly patient volume data were collected from
      seven Level I Trauma Centers. Additional information retrieved included monthly
      mortality, demographics, mean monthly injury severity (ISS), and trauma mechanism
      (blunt versus penetrating). Mortality was utilized as the primary study outcome.
      Statistical corrections for mean age, gender distribution, ISS, and mechanism of
      injury were made using analysis of co-variance (ANCOVA). Center-specific,
      annually-adjusted median monthly volumes (CSAA-MMV) were calculated to
      standardize patient volume differences across participating institutions.
      Statistical significance was set at alpha < 0.05. RESULTS: A total of 604 months
      of trauma admissions, encompassing 122,197 patients, were analyzed. Controlling
      for patient age, gender, ISS, and mechanism of injury, aggregate data suggested
      that monthly trauma volumes < 100 were associated with significantly greater
      mortality (3.9%) than months with volumes > 400 (mortality 2.9%, p < 0.01). To
      account for differences in monthly volumes between centers, as well as for
      temporal bias associated with potential differences over the entire study
      duration period, data were normalized using CSAA-MMV as a standardized reference
      point. Monthly volumes <= 33% of the CSAA-MMV were associated with adjusted
      mortality of 5.0% whereas monthly volumes >= 134% CSAA-MMV were associated with
      adjusted mortality of 2.7% (p < 0.01). CONCLUSIONS: This hypothesis-generating
      study suggests that greater monthly trauma volumes appear to be associated with
      lower mortality. In addition, our data also suggest that across all participating
      centers mortality may be a function of relative month-to-month volume variation.
      When normalized to institution-specific, annually-adjusted "median" monthly
      trauma contacts, we show that months with patient volumes <= 33% median may be
      associated with subtly but not negligibly (1.4-2.3%) higher mortality than months
      with patient volumes >= 134% median.

PMID- 29330634
TI  - Corrective osteotomies using patient-specific 3D-printed guides: a critical
      appraisal.
AB  - INTRODUCTION: Over the last decade, the technique of 3D planning has found its
      way into trauma surgery. The use of this technique in corrective osteotomies for
      treatment of malunions provides the trauma surgeon with a powerful tool. However,
      this technique is not entirely straightforward. We aimed to define potential
      pitfalls of this technique and possible solutions to overcome these shortcomings.
      MATERIALS AND METHODS: Ten patients with either a uni-, bi- or triplanar malunion
      of the long bones were included in this study. These patients were divided into
      three groups: a weight-bearing group and a non-weight-bearing group, the latter
      was divided into the humerus group and the forearm group, subsequently. 2D
      correction parameters were defined and compared within every group, as well as
      the interpretations of 3D visualization. RESULTS: The weight-bearing group
      revealed an undercorrection for almost all clinical measurements of the femur and
      tibia, while there was adequate matching of the osteotomies and of screw entry
      points in all cases. In the humerus group, coronal correction angles were nearly
      perfect in all cases, while axial and sagittal correction rates, however,
      differed substantially. Screw entry points and osteotomies were all at the level
      as planned. The forearm group showed undercorrection in multiple planes while
      there were good matching entry points for the screw trajectories. DISCUSSION:
      Four major pitfalls were encountered using the 3D printing technique: (1) careful
      examination of the planned guide positioning is mandatory, since suboptimal intra
      operative guide positioning is most likely the main cause of the incomplete
      correction; (2) the use of pre-drilled screw holes do not guarantee adequate
      screw positioning; (3) translation of bone fragments over the osteotomy planes in
      case of an oblique osteotomy is a potential hazard; (4) the depth of the
      osteotomy is hard to estimate, potentially leading to extensive cartilage damage.

PMID- 29330635
TI  - Hypotension due to spinal anesthesia influences fetal circulation in primary
      caesarean sections.
AB  - PURPOSE: Hypotension due to spinal anesthesia is a well-known side effect in
      pregnant women receiving caesarean section. Little is known about its impact on
      fetal blood circulation. METHODS: 40 women with uncomplicated singleton term
      pregnancies prepared for caesarean section were prospectively evaluated by
      Doppler sonography before and immediately after spinal anesthesia. RESULTS: In
      90% of the women, blood pressure significantly decreased after spinal anesthesia
      and 42.5% of the patients suffered from severe hypotension. We found a
      significant negative correlation between maternal blood pressure change and the
      resistant index (RI) of the umbilical artery (rs = - 0.376, p = 0.017) and a
      significant positive correlation between maternal blood pressure and fetal middle
      cerebral artery. CONCLUSION: Healthy fetuses seem to compensate well in
      situations with decreased uteroplacental blood flow due to maternal hypotension
      measured by means of RI changes in the fetal umbilical and middle cerebral
      artery. This raises the question if growth-restricted and/or preterm fetuses are
      able to compensate similarly or if general anesthesia would be a method of
      choice.

PMID- 29330636
TI  - A randomised trial comparing the pharmacokinetics and safety of the biosimilar CT
      P6 with reference trastuzumab.
AB  - PURPOSE: Access to trastuzumab, a valuable anti-cancer treatment, can be limited
      by cost. The primary aim of this study was to evaluate and compare the PK
      profiles of CT-P6, a biosimilar of trastuzumab, and US-licensed reference
      trastuzumab (Herceptin(r)) in healthy subjects. Secondary study aims included
      comparison of the safety and immunogenicity of CT-P6 and reference trastuzumab in
      these subjects. METHODS: We performed a single-dose, randomised, double-blind,
      parallel group study (NCT02665637) comparing CT-P6 with reference trastuzumab (6
      mg/kg, 90 min intravenous infusion) in 70 healthy adult males. Pharmacokinetics,
      safety and immunogenicity were evaluated up to 10 weeks post-dose. Primary
      endpoints were area under the serum concentration-time curve (AUC) from time 0 to
      infinity (AUCinf); AUC from time 0 to last quantifiable concentration (AUClast);
      and observed maximum serum concentration (Cmax). The pre-determined equivalence
      criterion was a 90% confidence interval of 80-125% for ratios of geometric least
      squares (LS) means. RESULTS: Equivalence of CT-P6 and reference trastuzumab was
      demonstrated. Ratios (CT-P6/reference trastuzumab) of geometric LS means (90%
      confidence interval) were: AUCinf 99.05 (93.00, 105.51); AUClast 99.30 (92.85,
      106.20); Cmax 96.58 (90.93, 102.59). Safety profiles were similar; treatment
      emergent adverse events occurred in ten subjects (28.6%) in the CT-P6 group and
      11 (31.4%) in the reference trastuzumab group. No serious adverse events or
      deaths occurred. No subjects tested positive for anti-drug antibodies.
      CONCLUSIONS: These data add to the totality of evidence required to demonstrate
      biosimilarity. A phase III study of CT-P6-in which equivalent neoadjuvant
      efficacy to reference trastuzumab has been demonstrated-is ongoing.

PMID- 29330637
TI  - Assessment of the permeability properties of cryopreservation outer bags used in
      NHSBT.
AB  - This study was carried out to investigate leakage/transport across the bag
      material of six outer cryopreservation bags in common use within NHS Blood and
      Transplant. In order to do this two different leak testing procedures; coloured
      dye and hydrogen tracer gas, were used. The data obtained show that a coloured
      dye cannot permeate through the materials both at room temperature and following
      storage at liquid nitrogen temperature (- 196  degrees C). In addition, when
      filled with the smallest elemental molecule, hydrogen, in the form of a tracer
      gas, all of the bags only allowed trace amounts of hydrogen to escape, either
      through the seal or the bag material. The data indicated that each of the bag
      materials tested would be capable of preventing bacterial or viral cross
      contamination as long as the material remained intact.

PMID- 29330638
TI  - Predictors of severe postoperative hyperglycemia after cardiac surgery in
      infants: a single-center, retrospective, observational study.
AB  - PURPOSE: Hyperglycemia is a common issue in infants after cardiac surgery for
      congenital heart disease. Poor glycemic control is suspected to be associated
      with adverse postoperative outcomes. This study was performed to investigate
      clinical factors contributing to hyperglycemia in the perioperative period in
      infats. METHODS: A total of 69 infants (aged 1-12 months) who were admitted to
      Yokohama City University Hospital Intensive Care Unit (ICU) after surgical repair
      of congenital heart diseases with cardiopulmonary bypass (CPB) were
      retrospectively analysed. Hyperglycemia was defined as blood glucose >= 250 mg/dL
      on ICU admission. Clinical background, operative factors, and postoperative
      factors were compared between the hyperglycemic and non-hyperglycemic groups.
      Additionally, multivariate analysis was performed to identify factors
      contributing to hyperglycemia. RESULTS: Nineteen (27.5%) and 50 (72.5%) infants
      were classified into the hyperglycemic and non-hyperglycemic groups,
      respectively. Hyperglycemic infants were significantly younger, shorter, and
      weighed less, with a higher rate of chromosomal abnormalities. Intraoperatively,
      they also experienced longer CPB and surgery times and had higher peak lactate
      levels and higher inotropic requirements. Hyperglycemia was related to longer
      mechanical ventilation and longer ICU stays. Multivariate analysis detected
      intraoperative hyperglycemia, longer CPB time, younger age and chromosomal
      abnormality as significant factors. CONCLUSION: Adding to hyperglycemia during
      the operation, longer CPB time younger age and chromosomal abnormality were
      identified as predictors of high blood glucose levels at ICU admission.

PMID- 29330639
TI  - Changes in tissue and cerebral oxygenation following spinal anesthesia in
      infants: a prospective study.
AB  - Use of spinal anesthesia (SA) in children may address concerns about potential
      neurocognitive effects of general anesthesia. We used near-infrared spectroscopy
      (NIRS) to assess the effects of SA on cerebral and tissue oxygenation in 19
      patients aged 7 +/- 3 months. Prior to SA placement, NIRS monitors were placed on
      the forehead (cerebral) and the thigh (tissue). Intraoperative cerebral and
      tissue saturation were 73 +/- 7 and 80 +/- 11%, respectively, before SA
      placement. NIRS measurements were monitored every minute for 30 min after SA
      placement and modeled using mixed-effects linear regression. Regression estimates
      showed that cerebral saturation remained stable from 67% [95% confidence interval
      (CI) 63, 71%] after SA placement to 68% (95% CI 65, 72%) at the conclusion of
      monitoring. After SA placement, tissue saturation was elevated compared to
      baseline values; but further change [from 91% (95% CI 89, 93%) to 93% (95% CI 91,
      95%) at the end of monitoring] was clinically non-significant. All patients
      breathed spontaneously on room air without changes in oxygen saturation. Blood
      pressure and heart rate decreased after SA placement, but no changes in
      hemodynamic parameters required treatment. These data provide further evidence of
      the neutral effect of SA on cerebral oxygenation 30 min after block placement.

PMID- 29330640
TI  - Is Contact with Children Related to Legitimizing Beliefs Toward Sex with Children
      Among Men with Pedophilia?
AB  - Among pedophilic men, social contact with children has been discussed as creating
      a risk situation for sexual abuse. Also, pedophilic men searching for such
      contact are seen as harboring more beliefs legitimizing sexual contact with
      children. However, social contact may also decrease false beliefs. We tested
      these competing views in an anonymous Internet survey with a non-forensic, non
      clinical sample of 104 self-classified pedophilic men. Results showed that both
      increased social and physical contact were significantly linked to fewer
      legitimizing beliefs toward sex with children, even when controlling for past
      psychotherapy, educational level, social desirability, and age. Controlling for
      previous conviction for child sexual offenses reduced the effect for physical
      contact, but not for social contact. Exploratory analyses showed that either type
      of contact had no significant effect on total self-perceived risk of offending.
      However, pedophilic men with physical contact with children perceived a higher
      risk of more direct (i.e., child abuse) than indirect offenses (i.e., child
      pornography offenses) compared to pedophilic men without physical contact.
      Despite limitations of the correlational design and the only small to moderate
      effects, the results challenge the assumption that complete avoidance of contact
      with children is necessary for persons with pedophilia to reduce the risk of
      abusive behavior.

PMID- 29330641
TI  - Characteristics of MUTYH variants in Japanese colorectal polyposis patients.
AB  - BACKGROUND: The base excision repair gene MUTYH is the causative gene of
      colorectal polyposis syndrome, which is an autosomal recessive disorder
      associated with a high risk of colorectal cancer. Since few studies have
      investigated the genotype-phenotype association in Japanese patients with MUTYH
      variants, the aim of this study was to clarify the clinicopathological findings
      in Japanese patients with MUTYH gene variants who were detected by screening
      causative genes associated with hereditary colorectal polyposis. METHODS: After
      obtaining informed consent, genetic testing was performed using target enrichment
      sequencing of 26 genes, including MUTYH. RESULTS: Of the 31 Japanese patients
      with suspected hereditary colorectal polyposis, eight MUTYH variants were
      detected in five patients. MUTYH hotspot variants known for Caucasians, namely
      p.G396D and p.Y179D, were not among the detected variants.Of five patients, two
      with biallelic MUTYH variants were diagnosed with MUTYH-associated polyposis,
      while two others had monoallelic MUTYH variants. One patient had the p.P18L and
      p.G25D variants on the same allele; however, supportive data for considering
      these two variants 'pathogenic' were lacking. CONCLUSIONS: Two patients with
      biallelic MUTYH variants and two others with monoallelic MUTYH variants were
      identified among Japanese colorectal polyposis patients. Hotspot variants of the
      MUTYH gene for Caucasians were not hotspots for Japanese patients.

PMID- 29330642
TI  - Meta-analysis of randomized clinical trials in the era of individual patient data
      sharing.
AB  - BACKGROUND: Individual patient data (IPD) meta-analysis is considered to be a
      gold standard when the results of several randomized trials are combined. Recent
      initiatives on sharing IPD from clinical trials offer unprecedented opportunities
      for using such data in IPD meta-analyses. METHODS: First, we discuss the evidence
      generated and the benefits obtained by a long-established prospective IPD meta
      analysis in early breast cancer. Next, we discuss a data-sharing system that has
      been adopted by several pharmaceutical sponsors. We review a number of
      retrospective IPD meta-analyses that have already been proposed using this data
      sharing system. Finally, we discuss the role of data sharing in IPD meta-analysis
      in the future. RESULTS: Treatment effects can be more reliably estimated in both
      types of IPD meta-analyses than with summary statistics extracted from published
      papers. Specifically, with rich covariate information available on each patient,
      prognostic and predictive factors can be identified or confirmed. Also, when
      several endpoints are available, surrogate endpoints can be assessed
      statistically. CONCLUSIONS: Although there are difficulties in conducting,
      analyzing, and interpreting retrospective IPD meta-analysis utilizing the
      currently available data-sharing systems, data sharing will play an important
      role in IPD meta-analysis in the future.

PMID- 29330643
TI  - Antihypertensive Medication and Dementia Risk in Older Adult African Americans
      with Hypertension: A Prospective Cohort Study.
AB  - BACKGROUND: African Americans are especially at risk of hypertension and
      dementia. Antihypertensive medications reduce the risk of cardiovascular events,
      but may also reduce the risk of dementia. OBJECTIVE: To assess the longitudinal
      effects of antihypertensive medications and blood pressure on the onset of
      incident dementia in a cohort of African Americans. DESIGN: Prospective cohort.
      PARTICIPANTS: 1236 community-dwelling patients from an inner-city public health
      care system, aged 65 years and older, with a history of hypertension but no
      history of dementia, and who had at least three primary care visits and a
      prescription filled for any medication. MAIN MEASURES: Blood pressure was the
      average of three seated measurements. Dementia was diagnosed using a two-stage
      design, with a screening evaluation every 2 to 3 years followed by a
      comprehensive in-home clinical evaluation for those with a positive screen.
      Laboratory, inpatient and outpatient encounter data, coded diagnoses and
      procedures, and medication records were derived from a health information
      exchange. KEY RESULTS: Of the 1236 hypertensive participants without dementia at
      baseline, 114 (9%) developed incident dementia during follow-up. Individuals
      prescribed any antihypertensive medication (n = 816) were found to have a
      significantly reduced risk of dementia (HR = 0.57, 95% CI 0.37-0.88, p = 0.0114)
      compared to untreated hypertensive participants (n = 420). When this analysis was
      repeated including a variable indicating suboptimally treated blood pressure (>
      140 mmHg systolic or >90 mmHg diastolic), the effect of antihypertensive
      medication was no longer statistically significant (HR = 0.65, 95% CI 0.32-1.30,
      p = 0.2217). CONCLUSIONS: Control of blood pressure in older adult African
      American patients with hypertension is a key intervention for preventing
      dementia, with similar benefits from most of the commonly available
      antihypertensive medications.

PMID- 29330644
TI  - Hydrocarbon Stapled Antimicrobial Peptides.
AB  - Antimicrobial peptides are promising candidates for anti-infective
      pharmaceuticals. Unfortunately, because of their low proteolytic and chemical
      stability, their usage is generally narrowed down to topical formulations. Until
      now, numerous approaches to increase peptide stability have been proposed. One of
      them, peptide hydrocarbon stapling, a modification based on stabilizing peptide
      secondary structure with a side-chain covalent hydrocarbon bridge, have been
      successfully applied to many peptides. Moreover, constraining secondary structure
      of peptides have also been proven to increase their biological activity. This
      review article describes studies on hydrocarbon stapled antimicrobial peptides
      with respect to improved drug-like properties.

PMID- 29330645
TI  - Delayed leptomeningeal metastasis of an adult anaplastic pilocytic astrocytoma.

PMID- 29330646
TI  - Potential impact of SGLT2 inhibitors on left ventricular diastolic function in
      patients with diabetes mellitus.
AB  - The pathogenesis of diabetes mellitus (DM)-related cardiac dysfunction is thought
      to be multifactorial, and possibly a key factor for the development of heart
      failure with preserved ejection fraction (HFpEF) in patients with DM and
      preserved left ventricular (LV) ejection fraction. Currently, there is no
      effective treatment for HFpEF, which is presented as LV diastolic dysfunction.
      Furthermore, it is well known that, in addition to DM, hypertension and
      overweight/obesity are also important factors associated with HFpEF. Sodium
      glucose cotransporter 2 (SGLT2) inhibitors are a new class of diabetic
      medications indicated only for the treatment of type 2 DM, and a recent clinical
      trial showed that patients with this disease and at high risk for cardiovascular
      events attained cardiovascular benefits from SGLT2 inhibitor in comparison with
      placebo efficacy. In addition to reduction of glycated hemoglobin levels in
      patients with type 2 DM, SGLT2 inhibitors are associated with weight loss and
      reductions in blood pressure. However, despite such intriguing results, it
      remains uncertain whether SGLT2 inhibitors are beneficial for LV diastolic
      function in patients with DM. This review deals with the impact of SGLT2
      inhibitors on LV diastolic function in patients with DM and their current
      potential for prevention of the future development of HFpEF in such patients.

PMID- 29330647
TI  - Absence of the Nitrous Oxide Reductase Gene Cluster in Commercial Alfalfa
      Inoculants Is Probably Due to the Extensive Loss of Genes During Rhizobial
      Domestication.
AB  - As other legume crops, alfalfa cultivation increases the emission of the
      greenhouse gas nitrous oxide (N2O). Since legume-symbiotic nitrogen-fixing
      bacteria play a crucial role in this emission, it is important to understand the
      possible impacts of rhizobial domestication on the evolution of denitrification
      genes. In comparison with the genomes of non-commercial strains, those of
      commercial alfalfa inoculants exhibit low total genome size, low number of ORFs
      and high numbers of both frameshifted genes and pseudogenes, suggesting a
      dramatic loss of genes during bacterial domestication. Genomic analysis focused
      on denitrification genes revealed that commercial strains have perfectly
      conserved the nitrate (NAP), nitrite (NIR) and nitric (NOR) reductase clusters
      related to the production of N2O from nitrate but completely lost the nitrous
      oxide (NOS) reductase cluster (nosRZDFYLX genes) associated with the reduction of
      N2O to gas nitrogen. Based on these results, we propose future screenings for
      alfalfa-nodulating isolates containing both nitrogen fixation and N2O reductase
      genes for environmental sustainability of alfalfa production.

PMID- 29330648
TI  - Cloning, expression and characterization of the esterase estUT1 from Ureibacillus
      thermosphaericus which belongs to a new lipase family XVIII.
AB  - A new esterase gene from thermophilic bacteria Ureibacillus thermosphaericus was
      cloned into the pET32b vector and expressed in Escherichia coli BL21(DE3).
      Alignment of the estUT1 amino acid sequence revealed the presence of a novel
      canonical pentapeptide (GVSLG) and 41-47% identity to the closest family of the
      bacterial lipases XIII. Thus the esterase estUT1 from U. thermosphaericus was
      assigned as a member of the novel family XVIII. It also showed a strong activity
      toward short-chain esters (C2-C8), with the highest activity for C2. When p
      nitrophenyl butyrate is used as a substrate, the temperature and pH optimum of
      the enzyme were 70-80  degrees C and 8.0, respectively. EstUT1 showed high
      thermostability and 68.9 +/- 2.5% residual activity after incubation at 70 
      degrees C for 6 h. Homology modeling of the enzyme structure showed the presence
      of a putative catalytic triad Ser93, Asp192, and His222. The activity of estUT1
      was inhibited by PMSF, suggesting that the serine residue is involved in the
      catalytic activity of the enzyme. The purified enzyme exhibited high stability in
      organic solvents. EstUT1 retained 85.8 +/- 2.4% residual activity in 30% methanol
      at 50  degrees C for 6 h. Stability at high temperature and tolerance to organic
      solvents make estUT1 a promising enzyme for biotechnology application.

PMID- 29330649
TI  - Growth of Leptospirillum ferriphilum in sulfur medium in co-culture with
      Acidithiobacillus caldus.
AB  - Leptospirillum ferriphilum and Acidithiobacillus caldus are both thermotolerant
      acidophilic bacteria that frequently co-exist in natural and man-made
      environments, such as biomining sites. Both are aerobic chemolithotrophs; L.
      ferriphilum is known only to use ferrous iron as electron donor, while A. caldus
      can use zero-valent and reduced sulfur, and also hydrogen, as electron donors. It
      has recently been demonstrated that A. caldus reduces ferric iron to ferrous when
      grown aerobically on sulfur. Experiments were carried out which demonstrated that
      this allowed L. ferriphilum to be sustained for protracted periods in media
      containing very little soluble iron, implying that dynamic cycling of iron
      occurred in aerobic mixed cultures of these two bacteria. In contrast, numbers of
      viable L. ferriphilum rapidly declined in mixed cultures that did not contain
      sulfur. Data also indicated that growth of A. caldus was partially inhibited in
      the presence of L. ferriphilum. This was shown to be due to greater sensitivity
      of the sulfur-oxidizer to ferric than to ferrous iron, and to highly positive
      redox potentials, which are characteristic of cultures containing Leptospirillum
      spp. The implications of these results in the microbial ecology of extremely
      acidic environments and in commercial bioprocessing applications are discussed.

PMID- 29330650
TI  - A cold-adapted endoglucanase from camel rumen with high catalytic activity at
      moderate and low temperatures: an anomaly of truly cold-adapted evolution in a
      mesophilic environment.
AB  - Endoglucanases are important enzymes in plant biomass degradation. They have
      current and potential applications in various industrial sectors including human
      and animal food processing, textile, paper, and renewable biofuel production. It
      is assumed that the cold-active endoglucanases, with high catalytic rates in
      moderate and cold temperatures, can improve the cost-effectiveness of industrial
      processes by lowering the need for heating and, thus, energy consumption. In this
      study, the endoglucanase CelCM3 was procured from a camel rumen metagenome via
      gene cloning and expression in Escherichia coli BL21 (DE3). The maximum activity
      of the enzyme on carboxymethyl cellulose (CMC) was obtained at pH 5 and 30 
      degrees C with a Vmax and Km of 339 U/mg and 2.57 mg/ml, respectively. The enzyme
      with an estimated low melting temperature of 45  degrees C and about 50% activity
      at 4  degrees C was identified to be cold-adapted. A thermodynamic analysis
      corroborated that CelCM3 with an activation energy (Ea), enthalpy of activation
      (DeltaH), and Gibb's free energy (DeltaG) of, respectively, 18.47 kJ mol-1, 16.12
      kJ mol-1, and 56.09 kJ mol-1 is a cold-active endoglucanase. In addition, CelCM3
      was tolerant of metal ions, non-ionic detergents, urea, and organic solvents.
      Given these interesting characteristics, CelCM3 shows promise to meet the
      requirements of industrial applications.

PMID- 29330651
TI  - 3D-computed tomography to compare the dimensions of the left atrial appendage in
      patients with normal sinus rhythm and those with paroxysmal atrial fibrillation.
AB  - Although paroxysmal atrial fibrillation (PAF) is an important cause of
      cardioembolic stroke, in contrast to chronic AF patients, the anatomical features
      of the left atrial appendage (LAA) in PAF patients remain unknown. Here, we
      investigated differences in LAA structures in patients with PAF and those with
      normal sinus rhythms (NSR) using 3D-computed tomography (3D-CT), which allows us
      to visualize complicated LAA structures at high spatial resolution. Study
      subjects were 30 consecutive PAF and 30 NSR patients with complete enhanced
      cardiac 3D-CT images available. After reconstruction of 3D LAA images, anatomical
      parameters of the LAA were measured and compared according to three proposed
      definitions of the LAA orifice plane determined by the following anatomical
      landmarks: DEF#1, center of warfarin ridge and centerline of proximal left
      circumflex artery; DEF#2, slope of warfarin ridge and mitral valve annulus;
      DEF#3, observers' discretion by progressive rotation using the observers' best
      estimate without the use of landmarks. The LAA volumes of the PAF groups were
      significantly greater than the NSR group according to all 3 definitions (DEF#1:
      1.43 times, DEF#2: 1.44 times, and DEF#3: 1.36 times greater). The LAA orifice
      area was significantly larger in PAF than in NSR according to DEF#2, but was
      similar by DEF#1 and DEF#3. Intra-observer and inter-observer variations for any
      LAA measurements were very low. In conclusion, 3D-CT-based quantitative
      assessment of the LAA provides highly reproducible and detailed measurements,
      which can successfully discriminate differences of LAA volume between patients
      with NSR and those with PAF, suggesting significantly greater volumes in the
      latter.

PMID- 29330653
TI  - Aurora D. Pryor, M.D.

PMID- 29330652
TI  - Dietary Management in the Immediate Preoperative Period of Bariatric Surgery: a
      National Overview : Bariatric Preoperative Diets.
AB  - BACKGROUND: Although widely applied, there is no consensus about the
      characteristics of the diets prescribed in the immediate preoperative period of
      bariatric surgery (BS). The objective of this study was to perform a survey on
      preoperative dietary management in BS centers. METHODS: This was a cross
      sectional study with BS Brazilian centers. Only BS centers with certificate of
      excellence by Surgical Review Corporation were included. An electronic
      questionnaire was applied to assess details about the dietary management in the
      immediate preoperative period of BS. RESULTS: Of the 15 centers invited, 80% (n =
      12) answered the questionnaire. Preoperative weight loss was required to patients
      in all 12 centers. For 8.3% (n = 1), this request was applied to all patients;
      91.7% (n = 11) of the centers requested weight loss in specific cases. Ten
      (83.3%) centers prescribed restrictive diets; none of these adopted a standard
      dietary protocol. The caloric value of the diets ranged from 800 to 2000
      kcal/day. The duration of the diet ranged from 10 to 20 days in 40% (n = 4) of
      the centers and from 20 to 90 days in 60% (n = 6) of the centers. Dietary
      prescription was based on team consensus in 100% (n = 12) of the centers. In
      33.3% (n = 4) of the centers, scientific evidence supporting dietary prescription
      was cited. CONCLUSION: This study identified the frequent practice of requesting
      preoperative weight loss and the diversity of diets used in the immediate
      preoperative period by Brazilian BS centers. Future guideline proposal is needed
      on preoperative BS diets.

PMID- 29330654
TI  - Risk Prediction Model for Severe Postoperative Complication in Bariatric Surgery.
AB  - BACKGROUND: Factors associated with risk for adverse outcome are important
      considerations in the preoperative assessment of patients for bariatric surgery.
      As yet, prediction models based on preoperative risk factors have not been able
      to predict adverse outcome sufficiently. OBJECTIVE: This study aimed to identify
      preoperative risk factors and to construct a risk prediction model based on
      these. METHODS: Patients who underwent a bariatric surgical procedure in Sweden
      between 2010 and 2014 were identified from the Scandinavian Obesity Surgery
      Registry (SOReg). Associations between preoperative potential risk factors and
      severe postoperative complications were analysed using a logistic regression
      model. A multivariate model for risk prediction was created and validated in the
      SOReg for patients who underwent bariatric surgery in Sweden, 2015. RESULTS:
      Revision surgery (standardized OR 1.19, 95% confidence interval (CI) 1.14-0.24, p
      < 0.001), age (standardized OR 1.10, 95%CI 1.03-1.17, p = 0.007), low body mass
      index (standardized OR 0.89, 95%CI 0.82-0.98, p = 0.012), operation year
      (standardized OR 0.91, 95%CI 0.85-0.97, p = 0.003), waist circumference
      (standardized OR 1.09, 95%CI 1.00-1.19, p = 0.059), and dyspepsia/GERD
      (standardized OR 1.08, 95%CI 1.02-1.15, p = 0.007) were all associated with risk
      for severe postoperative complication and were included in the risk prediction
      model. Despite high specificity, the sensitivity of the model was low.
      CONCLUSION: Revision surgery, high age, low BMI, large waist circumference, and
      dyspepsia/GERD were associated with an increased risk for severe postoperative
      complication. The prediction model based on these factors, however, had a
      sensitivity that was too low to predict risk in the individual patient case.

PMID- 29330655
TI  - Effectiveness for dentin hypersensitivity treatment of non-carious cervical
      lesions: a meta-analysis.
AB  - OBJECTIVE: The aim of this review is to conduct a systematic review and meta
      analysis comparing the effectiveness of in-home or in-office treatments for
      dentin hypersensitivity. MATERIALS AND METHODS: An electronic search without
      restriction on dates or languages was performed in four electronic databases
      until March 2017. In addition, hand-searches in regular journals and in the gray
      literature were also conducted. To develop the search strategy, clinical
      questions were formulated using the PICOS method. Eligibility criteria included
      randomized clinical trials (RCTs) that compared the effectiveness of different
      agents for the treatment of dentin hypersensitivity through chemical occlusion,
      physical occlusion, nerve desensitization, or photobiomodulation (low-level light
      therapy). This systematic review was registered in PROSPERO under number
      CRD42016039394. RESULTS: Twenty-five RCTs (16 parallel; 9 split-mouth), published
      from 1992 to 2016, were included. The results of the meta-analysis showed that in
      office subgroups treated with chemical or physical occlusion of dentin tubules
      and nerve desensitization had a statistically significant difference from
      placebo, with P < 0.00001, P < 0.00001, and P = 0.02, respectively. For in-home
      treatments, the results of the meta-analysis showed that only those subgroups
      treated with chemical occlusion of dentin tubules and nerve desensitization
      exhibited a statistically significant difference from placebo, with P < 0.00001
      and P = 0.03, respectively. CONCLUSIONS: The results of pairwise meta-analysis
      suggest that among in-office treatments, dentinal tubule occlusion (whether
      chemical or physical) and nerve desensitization provide the best outcomes for
      treatment of dentin hypersensitivity. For in-home treatments, only chemical
      occlusion of dentin tubules and nerve desensitization showed a greater treatment
      efficacy than placebo and the difference was statistically significant.

PMID- 29330657
TI  - The T1 shine through effect on susceptibility weighted imaging: an under
      recognized phenomenon.

PMID- 29330656
TI  - 3D imaging, 3D printing and 3D virtual planning in endodontics.
AB  - The adoption and adaptation of recent advances in digital technology, such as
      three-dimensional (3D) printed objects and haptic simulators, in dentistry have
      influenced teaching and/or management of cases involving implant, craniofacial,
      maxillofacial, orthognathic and periodontal treatments. 3D printed models and
      guides may help operators plan and tackle complicated non-surgical and surgical
      endodontic treatment and may aid skill acquisition. Haptic simulators may assist
      in the development of competency in endodontic procedures through the acquisition
      of psycho-motor skills. This review explores and discusses the potential
      applications of 3D printed models and guides, and haptic simulators in the
      teaching and management of endodontic procedures. An understanding of the
      pertinent technology related to the production of 3D printed objects and the
      operation of haptic simulators are also presented.

PMID- 29330658
TI  - Patient-specific model-based segmentation of brain tumors in 3D intraoperative
      ultrasound images.
AB  - PURPOSE: Intraoperative ultrasound (iUS) imaging is commonly used to support
      brain tumor operation. The tumor segmentation in the iUS images is a difficult
      task and still under improvement because of the low signal-to-noise ratio. The
      success of automatic methods is also limited due to the high noise sensibility.
      Therefore, an alternative brain tumor segmentation method in 3D-iUS data using a
      tumor model obtained from magnetic resonance (MR) data for local MR-iUS
      registration is presented in this paper. The aim is to enhance the visualization
      of the brain tumor contours in iUS. METHODS: A multistep approach is proposed.
      First, a region of interest (ROI) based on the specific patient tumor model is
      defined. Second, hyperechogenic structures, mainly tumor tissues, are extracted
      from the ROI of both modalities by using automatic thresholding techniques.
      Third, the registration is performed over the extracted binary sub-volumes using
      a similarity measure based on gradient values, and rigid and affine
      transformations. Finally, the tumor model is aligned with the 3D-iUS data, and
      its contours are represented. RESULTS: Experiments were successfully conducted on
      a dataset of 33 patients. The method was evaluated by comparing the tumor
      segmentation with expert manual delineations using two binary metrics: contour
      mean distance and Dice index. The proposed segmentation method using local and
      binary registration was compared with two grayscale-based approaches. The
      outcomes showed that our approach reached better results in terms of
      computational time and accuracy than the comparative methods. CONCLUSION: The
      proposed approach requires limited interaction and reduced computation time,
      making it relevant for intraoperative use. Experimental results and evaluations
      were performed offline. The developed tool could be useful for brain tumor
      resection supporting neurosurgeons to improve tumor border visualization in the
      iUS volumes.

PMID- 29330659
TI  - Coffee with a high content of chlorogenic acids and low content of
      hydroxyhydroquinone improves postprandial endothelial dysfunction in patients
      with borderline and stage 1 hypertension.
AB  - PURPOSE: The purpose of this study was to evaluate acute effects of coffee with a
      high content of chlorogenic acids and different hydroxyhydroquinone contents on
      postprandial endothelial dysfunction. METHODS: This was a single-blind,
      randomized, placebo-controlled, crossover-within-subject clinical trial. A total
      of 37 patients with borderline or stage 1 hypertension were randomized to two
      study groups. The participants consumed a test meal with a single intake of the
      test coffee. Subjects in the Study 1 group were randomized to single intake of
      coffee with a high content of chlorogenic acids and low content of
      hydroxyhydroquinone or coffee with a high content of chlorogenic acids and a high
      content of hydroxyhydroquinone with crossover. Subjects in the Study 2 group were
      randomized to single intake of coffee with a high content of chlorogenic acids
      and low content of hydroxyhydroquinone or placebo coffee with crossover.
      Endothelial function assessed by flow-mediated vasodilation and plasma
      concentration of 8-isoprostanes were measured at baseline and at 1 and 2 h after
      coffee intake. RESULTS: Compared with baseline values, single intake of coffee
      with a high content of chlorogenic acids and low content of hydroxyhydroquinone,
      but not coffee with a high content of chlorogenic acids and high content of
      hydroxyhydroquinone or placebo coffee, significantly improved postprandial flow
      mediated vasodilation and decreased circulating 8-isoprostane levels.
      CONCLUSIONS: These findings suggest that a single intake of coffee with a high
      content of chlorogenic acids and low content of hydroxyhydroquinone is effective
      for improving postprandial endothelial dysfunction. CLINICAL TRIAL REGISTRATION:
      URL for Clinical Trial: https://upload.umin.ac.jp ; Registration Number for
      Clinical Trial: UMIN000013283.

PMID- 29330660
TI  - Theobromine consumption does not improve fasting and postprandial vascular
      function in overweight and obese subjects.
AB  - BACKGOUND: Theobromine, a component of cocoa, may favorably affect conventional
      lipid-related cardiovascular risk markers, but effects on flow-mediated dilation
      (FMD) and other vascular function markers are not known. OBJECTIVE: To evaluate
      the effects of 4-week theobromine consumption (500 mg/day) on fasting and
      postprandial vascular function markers. DESIGN: In a randomized, double-blind
      crossover study, 44 apparently healthy overweight (N = 30) and obese (N = 14) men
      and women with low HDL-C concentrations, consumed daily 500 mg theobromine or
      placebo for 4 weeks. After 4 weeks, FMD, peripheral arterial tonometry (PAT),
      augmentation index (AIx), pulse wave velocity (PWV), blood pressure (BP) and
      retinal microvasculature measurements were performed. These measurements were
      carried out under fasting conditions and 2.5 h after a high-fat mixed meal
      challenge. RESULTS: 4-week theobromine consumption did not change fasting
      vascular function markers, except for a decrease in central AIx (cAIx, - 1.7 pp,
      P = 0.037) and a trend towards smaller venular calibers (- 2 um, P = 0.074).
      Consuming a high-fat mixed meal decreased FMD (0.89 pp, P = 0.002), reactive
      hyperemia index (RHI, - 0.30, P < 0.001), peripheral systolic BP (SBP, - 3 mmHg,
      P <= 0.001), peripheral diastolic BP (DBP, - 2 mmHg, P <= 0.001), central SBP (-
      6 mmHg, P <= 0.001) and central DBP (- 2 mmHg, P <= 0.001), but increased heart
      rate (HR, 2 bpm, P < 0.001). Theobromine did not modify these postprandial
      effects, but increased postprandially the brachial artery diameter (0.03 cm, P =
      0.015), and decreased the cAIx corrected for a HR of 75 (cAIx75, - 5.0 pp, P =
      0.004) and peripheral AIx (pAIx, - 6.3 pp, P = 0.017). CONCLUSION: Theobromine
      consumption did not improve fasting and postprandial endothelial function, but
      increased postprandial peripheral arterial diameters and decreased the AIx. These
      findings do not suggest that theobromine alone contributes to the proposed
      cardioprotective effects of cocoa. This trial was registered on
      clinicaltrials.gov under study number NCT02209025.

PMID- 29330661
TI  - Adipose tissue fatty acids present in dairy fat and risk of stroke: the Danish
      Diet, Cancer and Health cohort.
AB  - PURPOSE: The role of dairy fat for the risk of stroke is not yet clear. Adipose
      tissue reflects long-term fatty acid intake and metabolism. We, therefore,
      investigated associations for percentages of adipose tissue fatty acids, for
      which dairy products are a major source (12:0, 14:0, 14:1 cis-9, 15:0, 17:0, 18:1
      trans-11 and 18:2 cis-9, trans-11), with incident total stroke and stroke
      subtypes. METHODS: We conducted a case-cohort study within the Danish Diet,
      Cancer and Health cohort, including all incident stroke cases (n = 2108) and a
      random sample of the total cohort (n = 3186). The fatty acid composition of
      adipose tissue biopsies was determined by gas chromatography and specific fatty
      acids were expressed as percentage of total fatty acids. Stroke cases were
      identified in the Danish National Patient Registry and the diagnoses were
      individually verified. RESULTS: We recorded 2108 stroke cases of which 1745 were
      ischemic, 249 were intracerebral hemorrhages and 102 were subarachnoid
      hemorrhages. We observed a lower rate of ischemic stroke for a higher adipose
      tissue percentage of 12:0, 14:0, 15:0, 17:0, 18:1 trans-11 and 18:2 cis-9, trans
      11. Adipose tissue percentages of 15:0 and 18:1 trans-11 were also inversely
      associated with intracerebral hemorrhage, whereas no associations between the
      adipose tissue fatty acids and subarachnoid hemorrhage were observed. No
      associations between 14:1 cis-9 and ischemic or hemorrhagic stroke were found.
      CONCLUSIONS: Our results suggest that a larger percentage in adipose tissue of
      fatty acids for which dairy products are a major source is associated with a
      lower rate of ischemic stroke.

PMID- 29330662
TI  - Yogurt consumption is associated with higher nutrient intake, diet quality and
      favourable metabolic profile in children: a cross-sectional analysis using data
      from years 1-4 of the National diet and Nutrition Survey, UK.
AB  - PURPOSE: Yogurt consumption has been associated with higher nutrient intakes,
      better diet quality and improved metabolic profiles in adults. Few studies have
      investigated these associations in children. This study investigated the
      association of yogurt consumption with nutrient intakes, diet quality and
      metabolic profile in British children. METHODS: Data from  1687 children aged 4
      10 and 11-18 years of the National Diet and Nutrition Survey (NDNS) years 1-4
      were analysed. Yogurt consumption was determined using a 4-day diet diary. Diet
      quality was assessed by the Healthy Eating Index 2010 (HEI-2010). Anthropometric
      measures, blood pressure, pulse pressure, plasma glucose, HbA1c, C-reactive
      protein, triacylglycerol, total cholesterol, high-and low-density cholesterol
      from NDNS were used. RESULTS: The highest tertile of yogurt consumption (T3) was
      associated with higher nutrient intakes, particularly for calcium (children 4-10
      years: P < 0.0001; children 11-18 years P = 0.001), iodine (both age groups P <
      0.0001) and riboflavin (both age groups P < 0.0001), and HEI-2010 score (both age
      groups P < 0.0001) in children aged 4-10 years (mean +/- SD: 98.4 +/- 35.7 g
      yogurt/day) and 11-18 years (mean +/- SD: 105.4 +/- 37.5 g yogurt/day) compared
      with non-consumers (0 g yogurt/d). Yogurt consumption was associated with
      significantly lower pulse pressure in children aged 4-10 years and lower HbA1c
      concentration, being shorter and having a larger hip circumference in children
      aged 11-18 years, compared with non-yogurt consumers. CONCLUSION: This study
      suggests that British children who are yogurt consumers (> 60 g/day) have higher
      overall diet quality, nutrient intakes and adequacy, lower pulse pressure
      (children aged 4-10 years) and HbA1c concentrations (children aged 11-18 years),
      were shorter and had a smaller hip circumference (children aged 11-18 years).

PMID- 29330663
TI  - Human cytomegalovirus-encoded miR-UL112 contributes to HCMV-mediated vascular
      diseases by inducing vascular endothelial cell dysfunction.
AB  - Human cytomegalovirus (HCMV) infection has been linked to the pathogenesis of
      vasculopathy by inducing dysfunction of vascular cells such as endothelial cells.
      Hcmv-miR-UL112 is the most well-characterized HCMV-encoded microRNA occurring in
      the plasma of patients with cardiovascular diseases such as hypertension, while
      the specific underlying pathophysiological mechanisms are yet to be defined. The
      current study investigated the effect of hcmv-miR-UL112 on the growth and
      proliferation of human umbilical vascular endothelial cells (HUVECs); it might
      also be associated with signaling pathways. An adenovirus vector was designed and
      synthesized to stably express hcmv-miR-UL112 in HUVECs. Cell Counting Kit-8
      results showed that ectopically expressed hcmv-miR-UL112 can significantly
      increase the proliferation of HUVECs (p < 0.05). Flow cytometry revealed that the
      S-phase fraction in the cell cycle analysis was raised significantly after
      overexpression of hcmv-miR-UL112 (p < 0.05). Gene expression profile analysis,
      using the microarray technology, revealed 303 up-regulated and 62 down-regulated
      genes in HUVECs by comparing the AD-hcmv-miR-UL112-infected and control groups (p
      < 0.05 and > 2 fold change). Kyoto Encyclopedia of Genes and Genomes and Reactome
      Pathway, chosen as the functional annotation categories, were affected by hcmv
      miR-UL112 adenovirus vector. The significantly altered pathways mainly include
      the mitogen-activated protein kinase signaling pathway, cell adhesion molecules,
      chemokine signaling pathway, cytokine-cytokine receptor interaction, circadian
      rhythm-mammal, mineral absorption, protein processing in the endoplasmic
      reticulum, proximal tubule bicarbonate reclamation, vasopressin-regulated water
      reabsorption, and arachidonic acid metabolism. In conclusion, hcmv-miR-UL112
      could serve as a potential biomarker, and the miRNA-mediated regulation of
      signaling pathways might play significant roles in the physiological effects of
      hcmv-associated diseases.

PMID- 29330664
TI  - An Iranian genomic sequence of Beet mosaic virus provides insights into diversity
      and evolution of the world population.
AB  - Beet mosaic virus (BtMV), the only Potyvirus known to infect sugar beet, occurs
      worldwide in beet crops. The full genome sequencing of a BtMV isolate from Iran
      (Ir-VRU), enabled us to better understand the evolutionary history of this virus.
      Selection analysis suggested that BtMV evolution is mainly under negative
      selection but its strength varies in different proteins with the multifunctional
      proteins under strongest selection. Recombination has played a major role in the
      evolution of the BtMVs; only the Ir-VRU and USA isolates show no evidence of
      recombination. The ML phylogenies of BtMVs from coat protein and full sequences
      were completely congruent. The primary divergence of the BtMV phylogeny is into
      USA and Eurasian lineages, and the latter then divides to form a cluster only
      found in Iran, and a sister cluster that includes all the European and Chinese
      isolates. A simple patristic dating method estimated that the primary divergence
      of the BtMV population was only 360 (range 260-490) years ago, suggesting an
      emergence during the development of sugar beet as a crop over the past three
      centuries rather than with the use of leaf beet as a vegetable for at least 2000
      years.

PMID- 29330665
TI  - A synthetic pathway for the production of 2-hydroxyisovaleric acid in Escherichia
      coli.
AB  - Synthetic biology, encompassing the design and construction of novel artificial
      biological pathways and organisms and the redesign of existing natural biological
      systems, is rapidly expanding the number of applications for which biological
      systems can play an integral role. In the context of chemical production, the
      combination of synthetic biology and metabolic engineering approaches continues
      to unlock the ability to biologically produce novel and complex molecules from a
      variety of feedstocks. Here, we utilize a synthetic approach to design and build
      a pathway to produce 2-hydroxyisovaleric acid in Escherichia coli and demonstrate
      how pathway design can be supplemented with metabolic engineering approaches to
      improve pathway performance from various carbon sources. Drawing inspiration from
      the native pathway for the synthesis of the 5-carbon amino acid L-valine, we
      exploit the decarboxylative condensation of two molecules of pyruvate, with
      subsequent reduction and dehydration reactions enabling the synthesis of 2
      hydroxyisovaleric acid. Key to our approach was the utilization of an
      acetolactate synthase which minimized kinetic and regulatory constraints to
      ensure sufficient flux entering the pathway. Critical host modifications enabling
      maximum product synthesis from either glycerol or glucose were then examined,
      with the varying degree of reduction of these carbons sources playing a major
      role in the required host background. Through these engineering efforts, the
      designed pathway produced 6.2 g/L 2-hydroxyisovaleric acid from glycerol at 58%
      of maximum theoretical yield and 7.8 g/L 2-hydroxyisovaleric acid from glucose at
      73% of maximum theoretical yield. These results demonstrate how the combination
      of synthetic biology and metabolic engineering approaches can facilitate bio
      based chemical production.

PMID- 29330666
TI  - Heidegger, communication, and healthcare.
AB  - Communication between medical professionals and patients is an important aspect
      of therapy and patient satisfaction. Common barriers that get in the way of
      effective communication in this sphere include: (1) gender, age, and cultural
      differences; (2) physical or psychological discomfort or pain; (3) medical
      literacy; and (4) distraction due to technological factors or simply being
      overworked. The author examines these communicative barriers from a philosophical
      lens and then utilizes Martin Heidegger's phenomenology and hermeneutics to
      provide guidance for medical professional-patient interactions. The
      phenomenological approach espoused emphasizes the particular, contextual nature
      of such interactions, and thus is opposed to abstract, theoretical principles.
      Heidegger's hermeneutics provides a philosophical approach to communication that
      may guide the back-and-forth interpretation that should happen between medical
      professionals and patients to achieve effective communication.

PMID- 29330667
TI  - Diversity and Phenology of Wild Bees in a Highly Disturbed Tropical Dry Forest
      "Desierto de la Tatacoa", Huila-Colombia.
AB  - Colombian tropical dry forest is considered the most endangered tropical biome
      due to anthropic activities. Desierto de la Tatacoa (DsT) is an example of high
      disturbed tropical dry forest which still maintains a high biodiversity. The
      objective of the study was to record the diversity and phenology of wild bees in
      this place by monthly sampling between December 2014 and December 2016 in a 9-km2
      area. During the study, there was a prolonged El Nino-Southern Oscillation
      period. Bees were collected by entomological nets, malaise traps, eugenol scent
      trapping, and nest traps. Shannon index was calculated to estimate diversity and
      Simpson index to determine dominance of a species. The effect of environmental
      conditions (wet and dry season) in richness and abundance was analyzed by paired
      T tests. A total of 3004 bee specimens were collected, belonging to 80 species
      from Apidae, Megachilidae, Halictidae, and Colletidae. Apidae was the most
      diverse. Shannon index value was 2.973 (discarding Apis mellifera Linnaeus 1758
      data); thus, DsT can be considered as a zone of high wild bee diversity. Dry and
      rainy season showed differences in diversity (p < 0.05). Rainy season showed
      larger blooming periods and higher bee diversity than dry season. In both
      seasons, social species were dominant (e.g., A. mellifera or Trigona fulviventris
      Guerin 1844). Although DsT is a highly disturbed ecosystem, this study found it
      has the second highest number of genera and the fourth highest number of species
      reported in Colombia.

PMID- 29330669
TI  - Hip and Groin Injuries in Baseball Players.
AB  - PURPOSE OF REVIEW: To discuss the clinical significance of the most common hip
      and groin injuries in baseball players, as well as an algorithmic approach to
      diagnosis and treatment of these injuries. RECENT FINDINGS: (a) Limitations in
      throwing velocity, pitch control, and bat swing speed may be secondary to
      decreased mobility and strength within the proximal kinetic chain, which must
      harness power from the lower extremities and core. (b) Approximately 5.5% of all
      baseball injuries per year involve the hip/groin and may lead to a significant
      amount of time spent on the disabled list. Injuries involving the hip and groin
      are relatively common in baseball players. Our knowledge of the mechanics of
      overhead throwing continues to evolve, as does our understanding of the
      contribution of power from the lower extremities and core. It is paramount that
      the team physician be able to accurately diagnose and treat injuries involving
      the hip/groin, as they may lead to significant disability and inability to return
      to elite levels of play. This review focuses on hip- and groin-related injuries
      in the baseball player, including femoroacetabular impingement, core muscle
      injury, and osteitis pubis.

PMID- 29330668
TI  - Impact of duplicate CT scan rate after implementation of transfer image
      repository system at a level 1 trauma center.
AB  - PURPOSE: The regionalization of trauma in the USA results in frequent transfers
      of patients from a primary hospital ED to a higher level trauma facility. While
      many hospitals have a Picture Archive Communication System (PACS) which captures
      digital radiological images, these are often not available to the receiving
      institution resulting in duplicate imaging. The state of Arkansas instituted a
      trauma image repository (TIR) in July 2013. We examined whether implementation of
      this repository would impact CT scan duplication in the trauma system. METHODS:
      This was a retrospective analysis of trauma patients transferred from outlying
      hospitals in Arkansas and Missouri to a single level 1 trauma hospital in
      Missouri between July 2012 and June 2015. We compared the duplicate CT rate for
      patients transferred from Arkansas and Missouri hospitals before and after the
      repository was implemented for Arkansas. RESULTS: Prior to implementation (July
      2012-June 2013) of Arkansas TIR, duplicate CT rates were similar for patients
      transferred from Arkansas (11.5% +/- 2.8) or Missouri (16.3% +/- 7.5). Following
      implementation (July 2013-June 2014), the duplicate CT rate for patients
      transferred from Arkansas was significantly lower (Arkansas = 10.1% vs. Missouri
      16.2%; CI 95%, p = 0.02), and significance continued (Arkansas = 9.0% vs.
      Missouri = 17.8%; CI 95%, p = 0.02) during follow-up (July 2014-June 2015).
      CONCLUSION: Fewer patients received duplicated scans within the Arkansas as
      compared with the Missouri-based trauma referral systems regardless of Injury
      Severity Scores (ISS). Our findings suggest that TIR adoption coupled with PACS
      improved transferability of radiographic studies and could improve patient care
      while reducing costs in trauma transfers.

PMID- 29330670
TI  - Treatment of Partial Thickness Rotator Cuff Tears in Overhead Athletes.
AB  - PURPOSE OF REVIEW: To review the etiology, classification, presentation,
      evaluation, treatment strategy, and outcomes in overhead athletes with partial
      thickness rotator cuff tears. RECENT FINDINGS: Despite advances in surgical
      repair techniques, return to play following surgical repair of partial rotator
      cuff tears remains modest at best. Overhead athletes may be particularly prone to
      rotator cuff pathology due to the supraphysiological strains within the tendon
      during the throwing motion, as well as mechanical stress with contact between the
      undersurface of the rotator cuff and the glenoid. The true prevalence of partial
      tears may be underestimated given the high incidence of asymptomatic tears. Both
      dynamic ultrasound and enhanced contrast MRI have improved our understanding of
      this pathology. For most overhead athletes, nonoperative management is the most
      common course. Despite advances in imaging, diagnosis, and surgical techniques,
      our ability to return these patients to their elite level is modest at best when
      nonoperative management fails and surgical treatment is performed. If a surgical
      route is needed, debridement alone is the most frequent procedure given concerns
      of over constraint and poor return to play with surgical repair of the partial
      thickness rotator cuff tear.

PMID- 29330672
TI  - [Obituary for Prof. Dr. med. D. Sc. h.c. Robert F. Schmidt, Ph.D.]

PMID- 29330671
TI  - Internalizing and Externalizing Behaviors Share a Common Predictor: the Effects
      of Early Maladaptive Schemas Are Mediated by Coping Responses and Schema Modes.
AB  - We investigated the relationships of adolescents' internalizing and externalizing
      behaviors with their early maladaptive schemas (EMS), coping responses, and
      schema modes. We focused on EMS related to experiences of disconnection and
      rejection that comprise vulnerable emotions, such as shame, mistrust,
      deprivation, abandonment, and isolation/alienation. This cross-sectional study
      included a total of 699 adolescents (combined clinical and non-referred sample)
      who were 11 to 18 years old (M = 14.6; SD = 1.6), and of which 45% was male. All
      participants completed self-report questionnaires on EMS, coping responses,
      schema modes, and behavior problems. We aimed to clarify the relationships
      between these variables by testing mediation, moderation, and moderated mediation
      models. In general, coping responses functioned as mediators rather than
      moderators in the relationships between EMS and schema modes. Furthermore, EMS
      regarding experiences of disconnection and rejection were related to both
      internalizing and externalizing behavior problems, and coping responses and
      schema modes mediated these effects. In conclusion, although adolescent
      internalizing and externalizing behavior problems manifest quite differently,
      they seem related to the same EMS.

PMID- 29330673
TI  - Vacuum-assisted closure therapy of paradoxical reaction in tuberculous
      lymphadenopathy caused by Mycobacterium africanum.
AB  - A 26-year-old HIV-negative male from Ghana was treated for cervical,
      intrathoracic and abdominal lymph node tuberculosis (TB) and tuberculous
      hepatitis. Penetration of the thoracic trachea by a mediastinal lymph node had
      caused bronchomucosal TB. Sputum culture grew M. africanum, sensitive to all
      first-line antituberculous drugs. Four weeks after the beginning of directly
      observed treatment with isoniazid, rifampin, pyrazinamide and ethambutol, the
      right cervical lymph node increased in size, liquefied and caused a spontaneous
      fistula. A biopsy of the necrotized lymph node revealed rare acid-fast bacilli
      with a positive PCR for Mycobacterium tuberculosis complex. After debridement,
      vacuum-assisted closure therapy was performed for 6 weeks. Five months after the
      beginning of antituberculous therapy, a second paradoxical reaction occurred,
      with painful swelling of two contralateral supraclavicular lymph nodes.
      Extirpation of one node yielded a positive PCR for M. tuberculosis complex; the
      culture was negative. Antituberculous treatment was continued, and additional
      treatment with oral prednisolone 20 mg daily for 1 month tapering over 10 weeks
      was introduced, resulting in a decrease in lymphadenopathy. Antituberculous
      treatment was continued for a total of 9 months. The outcome was favorable, no
      further lymphadenopathy occurred over the following 6 months.

PMID- 29330675
TI  - Recognizing conserved non-canonical localization patterns of toll-like receptors
      in tissues and across species.
AB  - Toll-like receptors (TLR) 1, 2, 4, 5 and 6 were originally characterized as
      exclusively expressed on the cell surface and TLR 3, 7, 8 and 9 were said to be
      localized to the endosomes. However, continued research in this area shows that
      TLR localization may be altered across cell-types, and in response to
      stimulation, age or disease. Mucosal surfaces must remain tolerant to the
      commensal flora and thus intracellular or basal lateral localization of TLRs at
      mucosal surfaces may be necessary to prevent induction of an inflammatory
      response to commensal flora while still allowing the possibility for the
      receptors to prime an immune response when a pathogen has crossed the epithelial
      barrier. Here, we highlight the research specifying 'non-canonical' localization
      of TLRs in human and animal mucosal tissues and blood-derived cells, while
      excluding cultured polarized immortalized cells. Reports that only indicate TLR
      gene/protein expression and/or responsiveness to agonists have been excluded
      unless the report also indicates surface/intracellular distribution in the cell.
      Understanding the tissue- and species-specific localization of these specific
      pattern recognition receptors will lead to a greater appreciation of the way in
      which TLR ligands promote innate immunity and influence the adaptive immune
      response. A more comprehensive understanding of this information will potentially
      aid in the exploitation of the therapeutic or adjuvant potential of selectively
      localized TLRs and in opening new perspectives in understanding the basis of
      immunity.

PMID- 29330674
TI  - Advances in serological, imaging techniques and molecular diagnosis of Toxoplasma
      gondii infection.
AB  - BACKGROUND: Toxoplasmosis is worldwide distributed zoonotic infection disease
      with medical importance in immunocompromised patients, pregnant women and
      congenitally infected newborns. Having basic information on the traditional and
      new developed methods is essential for general physicians and infectious disease
      specialists for choosing a suitable diagnostic approach for rapid and accurate
      diagnosis of the disease and, consequently, timely and effective treatment.
      METHODS: We conducted English literature searches in PubMed from 1989 to 2016
      using relevant keywords and summarized the recent advances in diagnosis of
      toxoplasmosis. RESULTS: Enzyme-linked immunosorbent assay (ELISA) was most used
      method in past century. Recently advanced ELISA-based methods including
      chemiluminescence assays (CLIA), enzyme-linked fluorescence assay (ELFA),
      immunochromatographic test (ICT), serum IgG avidity test and immunosorbent
      agglutination assays (ISAGA) have shown high sensitivity and specificity. Recent
      studies using recombinant or chimeric antigens and multiepitope peptides method
      demonstrated very promising results to development of new strategies capable of
      discriminating recently acquired infections from chronic infection. Real-time PCR
      and loop-mediated isothermal amplification (LAMP) are two recently developed PCR
      based methods with high sensitivity and specificity and could be useful to early
      diagnosis of infection. Computed tomography, magnetic resonance imaging, nuclear
      imaging and ultrasonography could be useful, although their results might be not
      specific alone. CONCLUSION: This review provides a summary of recent developed
      methods and also attempts to improve their sensitivity for diagnosis of
      toxoplasmosis. Serology, molecular and imaging technologies each has their own
      advantages and limitations which can certainly achieve definitive diagnosis of
      toxoplasmosis by combining these diagnostic techniques.

PMID- 29330677
TI  - Evaluating Efficacy of Landsat-Derived Environmental Covariates for Predicting
      Malaria Distribution in Rural Villages of Vhembe District, South Africa.
AB  - Malaria in South Africa is still a problem despite existing efforts to eradicate
      the disease. In the Vhembe District Municipality, malaria prevalence is still
      high, with a mean incidence rate of 328.2 per 100,0000 persons/year. This study
      aimed at evaluating environmental covariates, such as vegetation moisture and
      vegetation greenness, associated with malaria vector distribution for better
      predictability towards rapid and efficient disease management and control. The
      2005 malaria incidence data combined with Landsat 5 ETM were used in this study.
      A total of nine remotely sensed covariates were derived, while pseudo-absences in
      the ratio of 1:2 (presence/absence) were generated at buffer distances of 0.5-20
      km from known presence locations. A stepwise logistic regression model was
      applied to analyse the spatial distribution of malaria in the area. A buffer
      distance of 10 km yielded the highest classification accuracy of 82% at a
      threshold of 0.9. This model was significant (rho < 0.05) and yielded a deviance
      (D2) of 36%. The significantly positive relationship (rho < 0.05) between the
      soil-adjusted vegetation index and malaria distribution at all buffer distances
      suggests that malaria vector (Anopheles arabiensis) prefer productive and greener
      vegetation. The significant negative relationship between water/moisture index
      (a1 index) and malaria distribution in buffer distances of 0.5, 10, and 20 km
      suggest that malaria distribution increases with a decrease in shortwave
      reflectance signal. The study has shown that suitable habitats of malaria vectors
      are generally found within a radius of 10 km in semi-arid environments, and this
      insight can be useful to aid efforts aimed at putting in place evidence-based
      preventative measures against malaria infections. Furthermore, this result is
      important in understanding malaria dynamics under the current climate and
      environmental changes. The study has also demonstrated the use of Landsat data
      and the ability to extract environmental conditions which favour the distribution
      of malaria vector (An. arabiensis) such as the canopy moisture content in
      vegetation, which serves as a surrogate for rainfall.

PMID- 29330679
TI  - ?

PMID- 29330676
TI  - Quantitative Outcomes of a One Health approach to Study Global Health Challenges.
AB  - Having gained momentum in the last decade, the One Health initiative promotes a
      holistic approach to address complex global health issues. Before recommending
      its adoption to stakeholders, however, it is paramount to first compile
      quantitative evidence of the benefit of such an approach. The aim of this scoping
      review was to identify and summarize primary research that describes monetary and
      non-monetary outcomes following adoption of a One Health approach. An extensive
      literature search yielded a total of 42,167 references, of which 85 were included
      in the final analysis. The top two biotic health issues addressed in these
      studies were rabies and malaria; the top abiotic health issue was air pollution.
      Most studies described collaborations between human and animal (n = 42), or human
      and environmental disciplines (n = 41); commonly reported interventions included
      vector control and animal vaccination. Monetary outcomes were commonly expressed
      as cost-benefit or cost-utility ratios; non-monetary outcomes were described
      using disease frequency or disease burden measurements. The majority of the
      studies reported positive or partially positive outcomes. This paper illustrates
      the variety of health challenges that can be addressed using a One Health
      approach, and provides tangible quantitative measures that can be used to
      evaluate future implementations of the One Health approach.

PMID- 29330678
TI  - [Quality indicators with reference values and threshold limits in general and
      visceral surgery : For obesity and metabolic, pancreatic, colon carcinoma and
      rectal carcinoma surgery].

PMID- 29330680
TI  - The illusion of control: Sequential dependencies underlie contingent attentional
      capture.
AB  - The degree to which humans have top-down control over which information they
      process remains a central debate within the attention literature. Most of the
      evidence supporting the top-down control of visuospatial attention has come from
      cueing paradigms in which target stimuli are preceded by cues that are similar or
      dissimilar from the target. These studies find that the cues similar to targets
      capture attention, but dissimilar cues do not, suggesting the top-down control of
      attention. Here, we used a modified cueing paradigm to investigate an alternative
      possibility that the cue type differences are due to sequential dependency
      effects occurring between cue and target processing rather than the top-down
      control of attention. When individuals searched for color targets, we replicated
      contingent capture effects in RTs, which are susceptible to sequential
      dependencies, but memory performance was always best at the cued locations,
      regardless of the cue's identity. When individuals searched for onset targets, we
      observed contingent capture in both tasks. These results demonstrate the utility
      of the memory probe paradigm and suggest an asymmetry between how strongly onsets
      and color defined cues capture attention.

PMID- 29330681
TI  - Verification of nonwords: The baseword frequency effect in children's
      pseudohomophone reading.
AB  - In this study, we investigated the baseword frequency effect in children and its
      implications for models of visual word recognition. The baseword frequency effect
      reflects the finding that response latencies in the lexical decision task to
      nonwords derived from high-frequency basewords (e.g., GREAN derived from GREEN)
      are shorter than for those derived from low-frequency basewords (e.g., SLEAT
      derived from SLEET). Importantly, the baseword frequency effect presents a
      challenge to current activation-based models of visual word recognition. One
      explanation for this effect is that the orthographic representations of high
      frequency basewords are easier to access. This allows a quick progression to a
      verification stage in which the exact spelling of a stimulus is checked, upon
      which the lexicality decision is then based. The main goal of this study was to
      investigate whether such a verification mechanism is specifically modulated by
      the quality of the orthographic lexicon. We tested whether the baseword frequency
      effect was evident in children's lexical decisions to pseudohomophones (PsH) and
      whether verification accuracy varied as a function of children's orthographic
      knowledge. The baseword frequency effect in response latency was observed in both
      German-speaking adults and children. Children's spelling skills significantly
      influenced the accuracy of the verification stage in their responses to PsH.
      These findings imply that verification is an integral part of word reading and
      thus should be included in computational models of visual word recognition.

PMID- 29330682
TI  - Life-Threatening Reaction with Topical 5-Fluorouracil.
AB  - A 67-year-old man developed a suspected adverse drug reaction during treatment
      with topical 5-fluorouracil (5-FU) for multiple actinic keratosis of the face,
      neck, and forearms. The man received topical 5-FU at a dosage of 0.5% for the
      actinic keratoses. After 1 week, he developed extreme lethargy, fatigue, fever,
      and mouth erosions. Several days later, and after discontinuation of 5-FU,
      painful mucositis and systemic side effects occurred, meeting criteria for
      hospitalization because of dehydration and a 6.8 kg weight loss.
      Hematology/oncology was consulted, and a possible systemic 5-FU reaction, similar
      to reactions to intravenous chemotherapy seen with a dihydropyrimidine
      dehydrogenase deficiency was suggested. The patient was not taking any concurrent
      medications, and he refused dihydropyrimidine dehydrogenase deficiency testing.

PMID- 29330683
TI  - Cardiac function during weaning failure: the role of diastolic dysfunction.
AB  - BACKGROUND: Cardiac dysfunction is a common cause of weaning failure. Weaning
      shares some similarities with a cardiac stress test and may challenge active
      phases of the cardiac cycle-like ventricular contractility and relaxation. This
      study aimed at assessing systolic and diastolic function during the weaning
      process and scrutinizing their dynamics during weaning trials. METHODS:
      Echocardiography was performed during baseline ventilator settings to assess
      cardiac function at the initiation of the weaning process and at the start and
      the end of consecutive weaning trials (performed at day-1, day-2, and before
      extubation if applicable) to explore the evolution of left ventricle
      contractility and relaxation in a subset of patients. RESULTS: Among 67 patients
      included, weaning was prolonged (>= 7 days) in 18 (27%) patients and short (< 7
      days) in 49 (73%). Prevalence of systolic dysfunction and isolated diastolic
      dysfunction before the initiation of weaning process were 37 and 17%,
      respectively. Isolated diastolic dysfunction was more frequent in patients with
      prolonged weaning as compared to their counterparts. Thirty-one patients were
      explored by echocardiography during consecutive weaning trials. An increase in
      filling pressures with an alteration of ventricular relaxation (as assessed by a
      decrease in tissue Doppler early mitral diastolic wave velocity) was found during
      failed weaning trials. CONCLUSIONS: Isolated diastolic dysfunction was associated
      with a prolongation of weaning. Increased filling pressures with left ventricle
      relaxation impairment may be a key mechanism of weaning trial failure.

PMID- 29330684
TI  - Investigation of Mature BDNF and proBDNF Signaling in a Rat Photothrombotic
      Ischemic Model.
AB  - Treatment with mature brain-derived neurotrophic factor (mBDNF) promotes
      functional recovery after ischemia in animal trials but the possible role of its
      precursor protein proBDNF and its receptors or the factors responsible for the
      conversion of proBDNF to mBDNF in ischemic stroke are not known. The main aim of
      this study was to characterize the time-dependent expression of genes and/or
      proteins related to BDNF processing and signaling after ischemia as well as the
      sensorimotor behavioral dysfunction in a photothrombotic ischemic model in rats.
      Characterization of different genes and proteins related to BDNF processing and
      signaling was performed using qPCR, immunoblotting and enzyme-linked
      immunosorbent assays. We showed in this study that some sensory and motor
      functional deficiencies appeared in the ischemic group at day 1 and persisted
      until day 14. Most changes in gene expression of BDNF and its processing enzymes
      occurred within the first 24 h in the ipsilateral cortex, but not in the
      contralateral cortex. At the protein level, proBDNF expression was increased at 6
      h, mBDNF expression was increased between 15 h and 1 day while p75 receptor
      protein expression was increased between 6 h and 3 days in the ipsilateral
      cortex, but not in the contralateral cortex. Therefore, cerebral ischemia in rats
      led to the up-regulation of genes and/or proteins of BDNF, proBDNF and their
      processing enzymes and receptors in a time-dependent manner. We propose that the
      balance between BDNF and proBDNF and their associated proteins may play an
      important role in the pathogenesis and recovery from ischemia.

PMID- 29330685
TI  - Do we understand the rationale behind driving restrictions in patients with an
      implantable cardioverter defibrillator?

PMID- 29330686
TI  - Attentional influences on memory formation: A tale of a not-so-simple story.
AB  - Is there a learning mechanism triggered by mere expectation violation? Is there
      some form of memory enhancement inherent to an event mismatching our predictions?
      Across seven experiments, we explore this issue by means of a validity paradigm.
      Although our manipulation clearly succeeded in generating an expectation and
      breaking it, the memory consequences of that expectation mismatch are not so
      obvious. We report here evidence of a null effect of expectation on memory
      formation. Our results (1) show that enhanced memory for unexpected events is not
      easily achieved and (2) call for a reevaluation of previous accounts of memory
      enhancements based on prediction error or difficulty of processing. Limitations
      of this study and possible implications for the field are discussed in detail.

PMID- 29330687
TI  - Evaluation of the Mitochondria-Related Redox and Bioenergetics Effects of
      Gastrodin in SH-SY5Y Cells Exposed to Hydrogen Peroxide.
AB  - Mitochondrion is the main site of ATP production in animal cells and also
      orchestrates signaling pathways associated with cell survival and death.
      Mitochondrial dysfunction has been linked to bioenergetics and redox impairment
      in human diseases, such as neurodegeneration and cardiovascular disease.
      Protective agents able to attenuate mitochondrial impairment are of
      pharmacological interest. Gastrodin (GAS; 4-hydroxybenzyl alcohol 4-O-beta-D
      glucoside) is a phenolic glucoside obtained from the Chinese herbal medicine
      Gastrodia elata Blume and exhibits antioxidant, anti-inflammatory, and
      antiapoptotic effects in several cell types. GAS is able to cross the blood-brain
      barrier, reducing the impact of different stressors on the cognition of
      experimental animals. In the present work, we investigated whether GAS would
      protect mitochondria of human SH-SY5Y neuroblastoma cells against an exposure to
      a pro-oxidant agent. The cells were treated with GAS at 25 MUM for 30 min before
      the administration of hydrogen peroxide (H2O2) at 300 MUM for an additional 3 or
      24 h, depending on the assay. We evaluated both mitochondrial redox state and
      function parameters and analyzed the mechanism by which GAS protected
      mitochondria in this experimental model. Silencing of the nuclear factor
      erythroid 2-related factor 2 (Nrf2) transcription factor suppressed the GAS
      induced mitochondrial protection seen here. Moreover, Nrf2 knockdown abrogated
      the effects of GAS on cell viability, indicating a potential role for Nrf2 in
      both mitochondrial and cellular protection promoted by GAS. Further research
      would be necessary to investigate whether GAS would be able to induce similar
      effects in in vivo experimental models.

PMID- 29330688
TI  - Hepatocyte nuclear factors as possible C-reactive protein transcriptional inducer
      in the liver and white adipose tissue of rats with experimental chronic renal
      failure.
AB  - Inflammation related to chronic kidney disease (CKD) is an important clinical
      problem. We recently determined that hepatocyte nuclear factor 1alpha (HNF1alpha)
      was upregulated in the livers of chronic renal failure (CRF) rats-experimental
      model of CKD. Considering that the promoter region of gene encoding C-reactive
      protein (CRP) contains binding sites for HNF1alpha and that the loss-of-function
      mutation in the Hnfs1alpha leads to significant reduction in circulating CRP
      levels, we hypothesized that HNF1alpha can activate the Crp in CRF rats. Here, we
      found coordinated upregulation of genes encoding CRP, interleukin-6 (IL-6),
      HNF1alpha, and HNF4alpha in the livers and white adipose tissue (WAT) of CRF
      rats, as compared to the pair-fed and control animals. This was accompanied by
      elevated serum levels of CRP and IL-6. CRP and HNFs' mRNA levels correlated
      positively with CRP and HNFs' protein levels in the liver and WAT. Similar
      upregulation of the Crp, Il-6, and Hnfs in the liver and WAT and increased serum
      CRP and IL-6 concentrations were found in lipopolysaccharide (LPS)-induced
      systemic inflammation in rats. Moreover, silencing HNF1alpha in HepG2 cells by
      small interfering RNA led to decrease in CRP mRNA levels. Our results suggests
      that (a) HNFs act in concert with IL-6 in the upregulation of CRP production by
      the liver and WAT, leading to an increase in circulating CRP concentration in CRF
      rats and (b) CRF-related inflammation plays an important role in the upregulation
      of genes that encode HNFs and CRP in the liver and WAT of CRF rats.

PMID- 29330689
TI  - The efficiency of acoustic radiation force impulse (ARFI) elastography in the
      diagnosis and staging of carpal tunnel syndrome.
AB  - OBJECTIVES: The aim of the present study was to quantify the stiffness of the
      median nerve (MN) at the carpal tunnel inlet by acoustic radiation force impulse
      (ARFI) elastography and to evaluate whether ARFI can be used in diagnosis and
      staging of carpal tunnel syndrome (CTS). METHODS: Sonographic examinations of 96
      wrists in 50 patients were included in the study. The cross-sectional area and
      stiffness of the MN were quantitatively measured by B-mode ultrasonography (USG)
      and ARFI. The findings of CTS were assigned to four groups: (I) normal (n = 21),
      (II) mild (n = 39), (III) moderate (n = 38), and (IV) severe (n = 19). The
      differences between CTS patients and controls and the differences in
      electrodiagnostic tests among subgroups were statistically compared. ROC analysis
      was performed to determine the cut-off values between subgroups. RESULTS:
      Bilateral CTS was present in 46 patients (92 wrists) and unilateral CTS in four
      patients. Of the 96 nerves in the 50 symptomatic "idiopathic CTS" patients (48
      women, 2 men; mean age 45.9 years, range 23-73 years), 39 (40.4%) were mild, 38
      (39.8%) were moderate, and 19 (19.8%) were severely affected. When compared to
      controls, MN stiffness was significantly higher in the CTS group (P < 0.001);
      furthermore, it was higher in the severe or extreme severity group than the mild
      or moderate severity group (P < 0.001). A 3.250 m/s cut-off value on ARFI
      revealed sensitivity, specificity, positive predictive value, negative predictive
      value, and accuracy of 81, 82, 95.1, 50, and 82%, respectively. CONCLUSION: The
      MN stiffness measured by ARFI elastography is significantly higher in patients
      with CTS then in controls. ARFI elastography appears to be a highly efficient
      imaging modality for the diagnosis and staging of these patients.

PMID- 29330690
TI  - Extracorporeal membrane oxygenation for severe Middle East respiratory syndrome
      coronavirus.
AB  - BACKGROUND: Middle East respiratory syndrome (MERS) is caused by a coronavirus
      (MERS-CoV) and is characterized by hypoxemic respiratory failure. The objective
      of this study is to compare the outcomes of MERS-CoV patients before and after
      the availability of extracorporeal membrane oxygenation (ECMO) as a rescue
      therapy in severely hypoxemic patients who failed conventional strategies.
      METHODS: We collected data retrospectively on MERS-CoV patients with refractory
      respiratory failure from April 2014 to December 2015 in 5 intensive care units
      (ICUs) in Saudi Arabia. Patients were classified into two groups: ECMO versus
      conventional therapy. Our primary outcome was in-hospital mortality; secondary
      outcomes included ICU and hospital length of stay. RESULTS: Thirty-five patients
      were included; 17 received ECMO and 18 received conventional therapy. Both groups
      had similar baseline characteristics. The ECMO group had lower in-hospital
      mortality (65 vs. 100%, P = 0.02), longer ICU stay (median 25 vs. 8 days,
      respectively, P < 0.01), and similar hospital stay (median 41 vs. 31 days, P =
      0.421). In addition, patients in the ECMO group had better PaO2/FiO2 at days 7
      and 14 of admission to the ICU (124 vs. 63, and 138 vs. 36, P < 0.05), and less
      use of norepinephrine at days 1 and 14 (29 vs. 80%; and 36 vs. 93%, P < 0.05).
      CONCLUSIONS: ECMO use, as a rescue therapy, was associated with lower mortality
      in MERS patients with refractory hypoxemia. The results of this, largest to date,
      support the use of ECMO as a rescue therapy in patients with severe MERS-CoV.

PMID- 29330691
TI  - Bis-guanylhydrazones as efficient anti-Candida compounds through DNA interaction.
AB  - Candida spp. are leading causes of opportunistic mycoses, including life
      threatening hospital-borne infections, and novel antifungals, preferably aiming
      targets that have not been used before, are constantly needed. Hydrazone- and
      guanidine-containing molecules have shown a wide range of biological activities,
      including recently described excellent antifungal properties. In this study, four
      bis-guanylhydrazone derivatives (BG1-4) were generated following a previously
      developed synthetic route. Anti-Candida (two C. albicans, C. glabrata, and C.
      parapsilosis) minimal inhibitory concentrations (MICs) of bis-guanylhydrazones
      were between 2 and 15.6 MUg/mL. They were also effective against preformed 48-h
      old C. albicans biofilms. In vitro DNA interaction, circular dichroism, and
      molecular docking analysis showed the great ability of these compounds to bind
      fungal DNA. Competition with DNA-binding stain, exposure of phosphatidylserine at
      the outer layer of the cytoplasmic membrane, and activation of metacaspases were
      shown for BG3. This pro-apoptotic effect of BG3 was only partially due to the
      accumulation of reactive oxygen species in C. albicans, as only twofold MIC and
      higher concentrations of BG3 caused depolarization of mitochondrial membrane
      which was accompanied by the decrease of the activity of fungal mitochondrial
      dehydrogenases, while the activity of oxidative stress response enzymes
      glutathione reductase and catalase was not significantly affected. BG3 showed
      synergistic activity with amphotericin B with a fractional inhibitory
      concentration index of 0.5. It also exerted low cytotoxicity and the ability to
      inhibit epithelial cell (TR146) invasion and damage by virulent C. albicans
      SC5314. With further developments, BG3 may further progress in the antifungal
      pipeline as a DNA-targeting agent.

PMID- 29330692
TI  - A new method for the in vitro determination of the bile tolerance of potentially
      probiotic lactobacilli.
AB  - A new in vitro method was developed to determine the bile tolerance of
      potentially probiotic lactobacilli. The overnight culture of various lactobacilli
      strains was inoculated into sterile, half-strength MRS broth supplemented with
      and without 0.3% (wt/vol) oxgall, buffered with 0.1 M sodium phosphate buffer at
      a final pH of 7.3, and incubated at 37  degrees C for 12 h under anaerobic
      conditions. The bile tolerance ability of the lactobacilli strains was expressed
      as the percentage of the propagation generations of the bacterial cells in the
      presence of oxgall to those in the absence of oxgall. The bile tolerance ability
      of 11 strains of 8 Lactobacillus species, including 3 bile salt hydrolase (BSH)
      negative strains and 8 BSH-positive strains, was analyzed using the newly
      developed method and two traditional methods. The results showed that bile
      tolerance ability of the strains was considerably different depending on the
      analysis method used. The newly developed method mimics the physiological
      environment of the human small intestine, and avoids changes in pH and bile salt
      composition during the incubation period, which are drawbacks of the traditional
      bile tolerance test methods. Therefore, the analysis method developed in this
      study is more suitable to screen or compare the bile tolerance ability of
      lactobacilli strains.

PMID- 29330693
TI  - The enhanced biomass and lipid accumulation in Coccomyxa subellipsoidea with an
      integrated treatment strategy initiated by brewery effluent and phytohormones.
AB  - Brewery effluent (BE) as an appreciable and sustainable resource presented new
      possibilities in low-cost algal biomass production, whereas the relatively low
      essential macronutrients hindered extensive applications as growth medium for
      microalgae cultivation. The objective of this study was to investigate the
      feasibility of an integrated treatment strategy initiated by BE coupling
      phytohormones in augmenting biomass and lipid accumulation in Coccomyxa
      subellipsoidea. Results revealed that BE coupling synthetic 1-naphthaleneacetic
      acid (NAA) accomplished the favorable lipid productivity of 481.76 mg/L/days,
      representing 6.80- to 9.71-fold more than that of single BE as well as standard
      Basal media. BE coupling NAA feeding also heightened the proportions of C16-C18
      fatty acids (over 96%) and mono-unsaturated C18:1 (approximate 45%) which were
      prone to high-quality biofuels-making. Such profound lipids accumulation might be
      attributable to that BE coupling NAA treatment drove most of metabolic flux (i.e.
      acetyl-CoA) derived from TCA cycle and glycolysis flowing into lipid accumulation
      pathway. Concurrently, the complete removal of total nitrogen and total
      phosphorus by C. subellipsoidea with assistance of NAA were easily complied with
      the permissible dischargeable limits for BE. These present results strongly
      demonstrated that BE coupling NAA was a potential feeding strategy in boosting
      algal lipid productivity and further provided great possibilities in linking
      affordable algal biomass production with high-efficient biological contaminants
      removal.

PMID- 29330694
TI  - Volatile compounds from beneficial or pathogenic bacteria differentially regulate
      root exudation, transcription of iron transporters, and defense signaling
      pathways in Sorghum bicolor.
AB  - KEY MESSAGE: Our results show that Sorghum bicolor is able to recognize bacteria
      through its volatile compounds and differentially respond to beneficial or
      pathogens via eliciting nutritional or defense adaptive traits. Plants establish
      beneficial, harmful, or neutral relationships with bacteria. Plant growth
      promoting rhizobacteria (PGPR) emit volatile compounds (VCs), which may act as
      molecular cues influencing plant development, nutrition, and/or defense. In this
      study, we compared the effects of VCs produced by bacteria with different
      lifestyles, including Arthrobacter agilis UMCV2, Bacillus methylotrophicus M4-96,
      Sinorhizobium meliloti 1021, the plant pathogen Pseudomonas aeruginosa PAO1, and
      the commensal rhizobacterium Bacillus sp. L2-64, on S. bicolor. We show that VCs
      from all tested bacteria, except Bacillus sp. L2-64, increased biomass and
      chlorophyll content, and improved root architecture, but notheworthy A. agilis
      induced the release of attractant molecules, whereas P. aeruginosa activated the
      exudation of growth inhibitory compounds by roots. An analysis of the expression
      of iron-transporters SbIRT1, SbIRT2, SbYS1, and SbYS2 and genes related to plant
      defense pathways COI1 and PR-1 indicated that beneficial, pathogenic, and
      commensal bacteria could up-regulate iron transporters, whereas only beneficial
      and pathogenic species could induce a defense response. These results show how S.
      bicolor could recognize bacteria through their volatiles profiles and highlight
      that PGPR or pathogens can elicit nutritional or defensive traits in plants.

PMID- 29330695
TI  - Glucosuria and all-cause mortality among general screening participants.
AB  - BACKGROUND: Dipstick urine tests are used for general health screening in Japan,
      but how the test results (e.g., glucosuria) relate to mortality is unknown.
      METHODS: Subjects participated in a nationwide screening in 2008 in six districts
      in Japan. We identified those who might have died using the national database of
      death certificates from 2008 to 2012 (total registered ~ 6 million) and verified
      candidates with the regional National Health Insurance Agency and public health
      nurses. Diabetes mellitus (DM) was defined as HbA1c >= 6.5%, fasting blood
      glucose >= 126 mg/dl, or medicated for DM. Hazard ratio (HR) and 95% confidence
      interval (CI) were calculated by Cox proportional hazard analysis. Glucosuria was
      defined as dipstick >= 1 +. RESULTS: Among 209,060 subjects, we identified 2714
      fatalities (median follow-up 3.57 years). Crude mortality rates were 1.2% for
      those without glucosuria and 3.4% for those with glucosuria. After adjusting for
      sex, age, body mass index, comorbidity (DM, hypertension, and dyslipidemia),
      history (stroke, heart disease, and kidney disease), and lifestyle (smoking,
      drinking, walking, and exercise), the HR (95% CI) for dipstick glucosuria was
      1.475 (1.166-1.849, P < 0.001). DM subjects with glucosuria (N = 4655) had a
      higher HR [1.302 (1.044-1.613, P = 0.020)] than DM subjects without glucosuria (N
      = 20,245), and non-DM subjects with glucosuria (N = 470) had a higher HR [2.511
      (1.539-3.833, P < 0.001)] than non-DM subjects without glucosuria (N = 183,690).
      CONCLUSION: Dipstick glucosuria significantly affected mortality in Japanese
      community-based screening participants.

PMID- 29330696
TI  - Migrant Live-in Caregivers Mental Health in Canada.
AB  - Empirical evidence suggests rapid health decline among temporary migrant workers
      but there is limited knowledge about their mental health. This study explored
      live-in care givers' (LCs) mental health and its determinants. Using a mixed
      methods design, a purposeful sample of 30 LCs was recruited. Data were collected
      through a selfcompleted questionnaire. A third of participants reported their
      mental health as poor or fair. Almost half experienced major depression. The poor
      mental health was associated with the average working hours and living
      accommodation. The average resiliency scores was moderately high and appeared to
      function as a protective factor against mental illness. Our findings suggest LCs
      are at risk of compromised mental health associated to their substandard working
      and living conditions. These conditions originates from violation of employment
      contracts, unfair employment practices, and the lack of enforcement of LCs' legal
      and human rights.

PMID- 29330697
TI  - Implementation of Dialectical Behavior Therapy in Residential Treatment Programs:
      A Process Evaluation Model for a Community-Based Agency.
AB  - Dialectical behavior therapy (DBT) can be challenging to implement in community
      based settings. Little guidance is available on models to evaluate the
      effectiveness or sustainability of training and implementation efforts.
      Residential programs have much to gain from introduction of evidence-based
      practices, but present their own challenges in implementation. This paper
      presents a low-cost process evaluation model to assess DBT training piloted in
      residential programs. The model targets staff and organizational factors
      associated with successful implementation of evidence-based practices and matches
      data collection to the four stages of the DBT training model. The strengths and
      limitations of the evaluation model are discussed.

PMID- 29330699
TI  - Accounting of GHG emissions and removals from forest management: a long road from
      Kyoto to Paris.
AB  - BACKGROUND: Forests have always played an important role in agreeing on
      accounting rules during the past two decades of international climate policy
      development. Starting from activity-based gross-net accounting of selected
      forestry activities to mandatory accounting against a baseline-rules have changed
      quite rapidly and with significant consequences for accounted credits and debits.
      Such changes have direct consequences on incentives for climate-investments in
      forestry. There have also been strong arguments not to include forests into the
      accounting system by considering large uncertainties, procedural challenges and a
      fear of unearned credits corrupting the overall accounting system, among others.
      This paper reflects the development of respective accounting approaches and
      reviews the progress made on core challenges and resulting incentives. MAIN TEXT:
      The historic development of forest management accounting rules is analysed in the
      light of the Paris Agreement. Pros and cons of different approaches are discussed
      with specific focus on the challenge to maintain integrity of the accounting
      approach and on resulting incentives for additional human induced investments to
      increase growth for future substitution and increased C storage by forest
      management. The review is solely based on scientific publications and official
      IPCC and UNFCC documents. Some rather political statements of non-scientific
      stakeholders are considered to reflect criticism. Such sources are indicated
      accordingly. Remaining and emerging requirements for an accounting system for
      post 2030 are highlighted. CONCLUSIONS: The Paris Agreement is interpreted as a
      "game changer" for the role of forests in climate change mitigation. Many
      countries rely on forests in their NDCs to achieve their self-set targets. In
      fact, the agreement "to achieve a balance between anthropogenic emissions by
      sources and removals by sinks of greenhouse gases in the second half of this
      century" puts pressure on the entire land sector to contribute to overall GHG
      emission reductions. This also concerns forests as a resource for the bio-based
      economy and wood products, and for increasing carbon reservoirs. By discussing
      the existing elements of forest accounting rules and conditions for establishing
      an accounting system post 2030, it is concluded that core requirements like
      factoring out direct human-induced from indirect human-induced and natural
      impacts on managed lands, a facilitation of incentives for management changes and
      providing safeguards for the integrity of the accounting system are not
      sufficiently secured by currently discussed accounting rules. A responsibility to
      fulfil these basic requirements is transferred to Nationally Determined
      Contributions. Increased incentives for additional human induced investments are
      not stipulated by the accounting approach but rather by the political decision to
      make use of the substitution effect and potential net removals from LULUCF to
      contribute to self-set targets.

PMID- 29330698
TI  - Circulating Hormones and Mammographic Density in Premenopausal Women.
AB  - Prior research suggests that several endogenous hormones in premenopausal women
      are associated with breast cancer risk; however, few studies have evaluated
      associations of endogenous hormones with mammographic density (MD) in
      premenopausal women. We conducted a cross-sectional study of plasma hormone
      levels in relation to MD among 634 cancer-free premenopausal women in the Nurses'
      Health Study II. We measured percent MD from screening mammograms using a
      computer-assisted method. We assayed estradiol, estrone, and estrone sulfate in
      blood samples timed in early follicular and mid-luteal phases of the menstrual
      cycle as well as testosterone, androstenedione, progesterone,
      dehydroepiandrosterone (DHEA), DHEA sulfate, sex hormone-binding globulin (SHBG),
      and anti-Mullerian hormone in luteal or untimed samples. We used multivariable
      linear regression to quantify the association of %MD with quartiles of each
      hormone, adjusting for age, body mass index, and breast cancer risk factors.
      Women in the highest quartile of follicular estradiol levels had significantly
      greater %MD compared to those in the lowest quartile [difference, 6.7 percentage
      points; 95% confidence interval (CI) 2.2, 11.3; p-trend < 0.001]. Similar
      associations were observed for follicular free estradiol but not luteal-phase
      estradiol. Also, women in the top (vs. bottom) quartile of free testosterone had
      significantly lower %MD (difference, - 4.7; 95% CI - 8.7, - 0.8; p-trend = 0.04).
      Higher SHBG was significantly associated with higher percent MD (difference, 4.8;
      95% CI 1.1, 8.6; p-trend = 0.002). Percent MD was not strongly associated with
      other measured hormones. Results were similar in analyses that excluded women
      with anovulatory cycles. Our findings suggest that follicular estradiol and SHBG
      may play an important role in premenopausal percent MD.

PMID- 29330700
TI  - Relation between internalizing behaviors, externalizing behaviors, and peer
      victimization among children with and without ADHD.
AB  - The current study explored the concurrent and longitudinal association between
      internalizing behaviors, externalizing behaviors, and peer victimization among
      children with and without ADHD. Eighty children (42 ADHD, 38 non-ADHD) ages 8-12
      participated in the present study conducted over a 6-month period. During the
      baseline session, parents completed a structured diagnostic interview and the
      Vanderbilt ADHD Parent Rating Scale to determine whether their child met criteria
      for ADHD, and the Child Behavior Checklist (CBCL) to assess their child's
      internalizing and externalizing behaviors; children completed the Perception of
      Peer Support Scale (PPSS) to assess experiences of peer victimization. At the 6
      month follow-up session, parents completed the CBCL and children completed the
      PPSS. Concurrently, internalizing behaviors were associated with peer
      victimization among children with and without ADHD; ADHD moderated this relation,
      such that internalizing behaviors were more strongly related to peer
      victimization among children with ADHD. Longitudinally, internalizing behaviors
      at baseline predicted peer victimization at 6-month follow-up; however, further
      analyses demonstrated there was a covarying change in internalizing behaviors and
      peer victimization. These findings suggest internalizing behaviors are related to
      peer victimization concurrently, and over time, and are associated with increased
      risk for peer victimization in the presence of ADHD. Additionally, internalizing
      behaviors and peer victimization appear to share a dynamic relationship; that is,
      decreases in internalizing behaviors predict similar decreases in peer
      victimization. No significant relations were observed between externalizing
      behaviors and peer victimization. Implications and limitations are discussed.

PMID- 29330701
TI  - ?

PMID- 29330702
TI  - pTAC10, an S1-domain-containing component of the transcriptionally active
      chromosome complex, is essential for plastid gene expression in Arabidopsis
      thaliana and is phosphorylated by chloroplast-targeted casein kinase II.
AB  - In higher plant chloroplasts, the plastid-encoded RNA polymerase (PEP) consists
      of four catalytic subunits and numerous nuclear-encoded accessory proteins,
      including pTAC10, an S1-domain-containing protein. In this study, pTAC10 knockout
      lines were characterized. Two ptac10 mutants had an albino phenotype and severely
      impaired chloroplast development. The pTAC10 genomic sequence fused to a four
      tandem MYC tag driven by its own promoter functionally complemented the ptac10-1
      mutant phenotype. pTAC10 was present in both the chloroplast stroma and
      thylakoids. Two-dimensional blue native polyacrylamide gel electrophoresis (BN
      PAGE), and immunoblotting assays showed that pTAC10:MYC co-migrates with one of
      the PEP core subunits, RpoB. A comprehensive investigation of the plastid gene
      expression profiles by quantitative RT-PCR revealed that, compared with wild-type
      plants, the abundance of PEP-dependent plastid transcripts is severely decreased
      in the ptac10-1 mutant, while the amount of plastid transcripts exclusively
      transcribed by NEP either barely changes or even increases. RNA blot analysis
      confirmed that PEP-dependent chloroplast transcripts, including psaB, psbA and
      rbcL, substantially decrease in the ptac10-1 mutant. Immunoblotting showed
      reduced accumulation of most chloroplast proteins in the ptac10 mutants. These
      data indicate the essential role of pTAC10 in plastid gene expression and plastid
      development. pTAC10 interacts with chloroplast-targeted casein kinase 2 (cpCK2)
      in vitro and in vivo and can be phosphorylated by Arabidopsis cpCK2 in vitro at
      sites Ser95, Ser396 and Ser434. RNA-EMSA assays showed that pTAC10 is able to
      bind to the psbA, atpE and accD transcripts, suggesting a non-specific RNA
      binding activity of pTAC10. The RNA affinity of pTAC10 was enhanced by
      phosphorylation and decreased by the amino acid substitution Ser434-Ala of
      pTAC10. These data show that pTAC10 is essential for plastid gene expression in
      Arabidopsis and that it can be phosphorylated by cpCK2.

PMID- 29330703
TI  - Association Between Atrial, Ventricular and Vascular Morphofunctional Alterations
      in Rheumatoid Arthritis.
AB  - INTRODUCTION: Rheumatoid arthritis (RA) represents a risk of non-fatal and
      cardiovascular events. The aim of the present study was to evaluate
      simultaneously left and right atrial and ventricular function, as well as
      arterial stiffness, in RA patients. METHODS: This cross-sectional study included
      55 consecutive RA patients and 55 healthy age and gender-matched controls. Blood
      pressure and arterial stiffness were assessed in all participants, who also
      underwent a complete echocardiographic examination. RESULTS: RA patients were
      treated with steroid therapy (52.7%), methotrexate (66.6%) and biological therapy
      (54.5%). Disease activity score revealed low average RA activity. Augmentation
      index was significantly higher in RA patients (32.2 +/- 8.6 vs. 28.4 +/- 8.9%, P
      = 0.02). Left atrial volume was also higher among RA patients (23.1 +/- 8.2 vs.
      20.1 +/- 7.1 ml/m2, P = 0.04), whereas mitral and tricuspid E/A ratios were
      significantly lower in RA individuals (0.90 +/- 0.24 vs. 1.03 +/- 0.35, P = 0.02;
      1.07 +/- 0.31 vs. 1.27 +/- 0.35, P = 0.003, respectively). Tissue Doppler
      systolic and diastolic velocities were similar between the observed groups.
      Arterial stiffness index showed significant correlation with disease duration (r
      = 0.29; P = 0.03). Tissue Doppler-derived transmitral late diastolic velocity
      (A') showed significant correlation with index of disease activity in the RA
      patients. CONCLUSIONS: Our results showed that left and right ventricular
      diastolic function and arterial stiffness were significantly deteriorated in the
      RA patients comparing with controls. The assessment of left and right ventricular
      diastolic function, as well as vascular function, should be an essential part of
      clinical evaluation in the RA patients.

PMID- 29330704
TI  - The Effects of Coenzyme Q10 Supplementation on Blood Pressures Among Patients
      with Metabolic Diseases: A Systematic Review and Meta-analysis of Randomized
      Controlled Trials.
AB  - INTRODUCTION: Although several trials have assessed the effect of coenzyme Q10
      (CoQ10) supplementation on blood pressures among patients with metabolic
      diseases, findings are controversial. AIM: This review of randomized controlled
      trials (RCTs) was performed to summarize the evidence on the effects of CoQ10
      supplementation on blood pressures among patients with metabolic diseases.
      METHODS: Randomized-controlled trials (RCTs) published in PubMed, EMBASE, Web of
      Science and Cochrane Library databases up to 10 August 2017 were searched. Two
      review authors independently assessed study eligibility, extracted data, and
      evaluated risk of bias of included studies. Heterogeneity was measured with a Q
      test and with I2 statistics. Data were pooled by using the fix or random-effect
      model based on the heterogeneity test results and expressed as standardized mean
      difference (SMD) with 95% confidence interval (CI). RESULTS: A total of seventeen
      randomized controlled trials (684 participants) were included. Results showed
      that CoQ10 supplementation significantly decreased systolic blood pressure (SBP)
      (SMD - 0.30; 95% CI - 0.52, - 0.08). However, CoQ10 supplementation decreased
      diastolic blood pressure (DBP), but this was not statistically significant (SMD -
      0.08; 95% CI - 0.46, 0.29). CONCLUSIONS: CoQ10 supplementation may result in
      reduction in SBP levels, but did not affect DBP levels among patients with
      metabolic diseases. Additional prospective studies regarding the effect of CoQ10
      supplementation on blood pressure in patients with metabolic diseases are
      necessary.

PMID- 29330705
TI  - Association between skeletal morphology and agenesis of all four third molars in
      Japanese orthodontic patients.
AB  - The purpose of this study was to clarify differences in skeletal morphologies
      between male and female orthodontic patients with and without agenesis of all
      four third molars. A total of 64 patients (32 males and 32 females) with agenesis
      of all four third molars without agenesis of other teeth were selected as the
      third molars agenesis group (group 1). In addition, 64 patients (32 males and 32
      females) with all these teeth were selected as controls (group 2). Lateral
      cephalograms taken between the ages of 14 and 30 years were used to compare
      skeletal morphology between groups 1 and 2 and between sexes. Maxillary length (P
      < 0.001), lower facial height (P < 0.05), gonial angle (P < 0.001) and mandibular
      plane angle (P < 0.001) were significantly smaller in group 1 than in group 2.
      Irrespective of the presence or absence of all four third molars, males had
      significantly smaller lower facial height (P < 0.01) and mandibular plane angle
      (P < 0.001) and significantly greater total mandibular length (P < 0.001),
      mandibular body length (P < 0.001) and mandibular ramus height (P < 0.001) than
      females. Japanese orthodontic patients with agenesis of all four third molars had
      significantly small maxillary length, lower facial height, gonial angle and
      mandibular plane angle.

PMID- 29330706
TI  - Color stability of different composite resins after polishing.
AB  - The goals of the present study were to evaluate, in vitro, the staining of
      different composite resins submitted to different common beverages, and to
      compare the staining effect of each of these solutions. A total of 288 specimens
      were randomly divided into six groups and immersed for 4 weeks in five staining
      solutions represented by red wine, orange juice, coke, tea and coffee or in
      artificial saliva as a control group. When analyzed over a black background, mean
      DeltaE00 values varied from 0.8 for Venus Diamond, Saremco Microhybrid and ELS in
      saliva and Estelite Posterior in coke to 37.6 for Filtek Supreme in red wine.
      When analyzed over a white background, mean DeltaE00 values varied from 0.5 for
      Saremco Microhybrid in saliva to 51.1 for Filtek Supreme in red wine. All
      materials showed significant changes in color after 4 weeks of immersion in
      staining solutions. Significant differences were found between the tested
      composite resins and also between the staining solutions.

PMID- 29330707
TI  - Effects of periodontal treatment on carotid intima-media thickness in patients
      with lifestyle-related diseases: Japanese prospective multicentre observational
      study.
AB  - Atherosclerosis, a chronic inflammatory disease in arterial blood vessels, is one
      of the major causes of death in worldwide. Meanwhile, periodontal disease is a
      chronic inflammatory disease caused by infection with periodontal pathogens such
      as P. gingivalis (Porphyromonas gingivalis). Several studies have reported
      association between periodontal infection and atherosclerosis, but direct
      investigation about the effects of periodontal treatment on atherosclerosis has
      not been reported. We have planned Japanese local clinics to determine the
      relationship between periodontal disease and atherosclerosis under collaborative
      with medical and dental care. A prospective, multicentre, observational study was
      conducted including 38 medical patients with lifestyle-related diseases in the
      stable period under consultation at participating medical clinics and 92
      periodontal patients not undergoing medical treatment but who were consulting at
      participating dental clinics. Systemic and periodontal examinations were
      performed before and after periodontal treatment. At baseline, LDL-C (low-density
      lipoprotein cholesterol) levels and percentage (%) of mobile teeth were
      positively related to plasma IgG (immunoglobulin) antibody titer against P.
      gingivalis with multivariate analysis. Corresponding to improvements in
      periodontal clinical parameters after treatment, right and left max IMT (maximum
      intima-media thickness) levels were decreased significantly after treatment (SPT
      S: start of supportive periodontal therapy, SPT-1y: at 1 year under SPT, and SPT
      3y: at 3 years under SPT). The present study has clarified our previous
      univariate analysis results, wherein P. gingivalis infection was positively
      associated with progression of atherosclerosis. Thus, routine screening using
      plasma IgG antibody titer against P. gingivalis and periodontal treatment under
      collaborative with medical and dental care may prevent cardiovascular accidents
      caused by atherosclerosis.

PMID- 29330708
TI  - Living with lymphoedema-the perspective of cancer patients: a qualitative study.
AB  - PURPOSE: The aim of this study was to describe the lived experience of
      lymphoedema and the barriers faced by cancer sufferers receiving physiotherapy
      outpatient treatment. METHODS: A qualitative, phenomenological study was
      performed. Purposeful sampling method was used. Data collection methods included
      unstructured and semi-structured interviews and researcher field notes. A
      thematic analysis was used. The study was conducted following the Consolidated
      Criteria for Reporting Qualitative Research guidelines. RESULTS: Eleven patients
      (62.18 +/- 10.14 years) (90.91% women) participated. One theme was identified
      with different subgroups. The main theme 'Living a life with multiple barriers'
      formed by the subthemes 'Discovering physical and psychological barriers',
      'Searching information', 'Building relationships' and 'Controlling expenses'
      displays the daily difficulties they must face in areas such as work. The
      patients reported that lymphoedema is a constant emotional and physical
      challenge. They need to adapt their lives to their new situation, learning how to
      manage the lymphoedema. CONCLUSIONS: Patients considered lymphoedema as a
      clinical situation with multiple barriers and they found that it does alter their
      quality of life. These results can be applied in onco-haematology units to
      develop specific protocols for customers.

PMID- 29330710
TI  - Glycogen Production in Marine Cyanobacterial Strain Synechococcus sp. NKBG
      15041c.
AB  - An important feature offered by marine cyanobacterial strains over freshwater
      strains is the capacity to grow in seawater, replacing the need for often-limited
      freshwater. However, there are only limited numbers of marine cyanobacteria that
      are available for genetic manipulation and bioprocess applications. The marine
      unicellular cyanobacteria Synechococcus sp. strain NKBG 15041c (NKBG15041c) has
      been extensively studied. Recombinant DNA technologies are available for this
      strain, and its genomic information has been elucidated. However, an
      investigation of carbohydrate production, such as glycogen production, would
      provide information for inevitable biofuel-related compound production, but it
      has not been conducted. In this study, glycogen production by marine
      cyanobacterium NKBG15041c was investigated under different cultivation
      conditions. NKBG15041c yielded up to 399 MUg/ml/OD730 when cells were cultivated
      for 168 h in nitrogen-depleted medium (marine BG11DeltaN) after medium
      replacement (336 h after inoculation). Cultivation under nitrogen-limited
      conditions also yielded an accumulation of glycogen in NKBG15041c cells (1 mM
      NaNO3, 301 MUg/ml/OD730; 3 mM NaNO3, 393 MUg/ml/OD730; and 5 mM NaNO3, 328
      MUg/ml/OD730) under ambient conditions. Transcriptional analyses were carried out
      for 13 putative genes responsible for glycogen synthesis and catabolism that were
      predicted based on homology analyses with Synechocystis sp. PCC 6803 (PCC6803)
      and Synechococcus sp. PCC7002 (PCC7002). The transcriptional analyses revealed
      that glycogen production in NKBG15041c under nitrogen-depleted conditions can be
      explained by the contribution of both increased carbon flux towards glycogen
      synthesis, similar to PCC6803 and PCC7002, and increased transcriptional levels
      of genes responsible for glycogen synthesis, which is different from the
      conventionally reported phenomenon, resulting in a relatively high amount of
      glycogen under ambient conditions compared to PCC6803 and PCC7002.

PMID- 29330712
TI  - Correction to: Pre-existing Small Vessel Disease in Patients with Acute Stroke
      from the Middle East, Southeast Asia, and Philippines.
AB  - The author names "Dr. Pablo Garcia Bermejo" and "Dr. Muhammad Faisal Wadiwala"
      needed to be added as the 6th and 7th authors, respectively. The authors regret
      this error.

PMID- 29330709
TI  - In vitro and in vivo activity of iclaprim, a diaminopyrimidine compound and
      potential therapeutic alternative against Pneumocystis pneumonia.
AB  - Pneumocystis pneumonia is a serious complication that may affect immunosuppressed
      patients. The absence of reliable and safe therapeutic alternatives to
      trimethoprim-sulfamethoxazole (TMP/SMX) justifies the search for more effective
      and less toxic agents. In this study, the in vitro and in vivo anti-Pneumocystis
      jirovecii activity of iclaprim, a diaminopyrimidine compound that exerts its
      antimicrobial activity through the inhibition of dihydrofolate reductase (DHFR),
      as does TMP, was evaluated alone or in combination with SMX. The antimicrobial
      activity of iclaprim was tested in vitro using an efficient axenic culture
      system, and in vivo using P. carinii endotracheally inoculated corticosteroid
      treated rats. Animals were orally administered iclaprim (5, 25, 50 mg/kg/day),
      iclaprim/SMX (5/25, 25/125, 50/250 mg/kg/day), TMP (50 mg/kg/day), or TMP/SMX
      (50/250 mg/kg/day) once a day for ten consecutive days. The in vitro maximum
      effect (Emax) and the drug concentrations needed to reach 50% of Emax (EC50) were
      determined, and the slope of the dose-response curve was estimated by the Hill
      equation (Emax sigmoid model). The iclaprim EC50 value was 20.3 MUg/mL. This
      effect was enhanced when iclaprim was combined with SMX (EC50: 13.2/66 MUg/mL) (p
      = 0.002). The TMP/SMX EC50 value was 51.4/257 MUg/mL. In vivo, the iclaprim/SMX
      combination resulted in 98.1% of inhibition compared to TMP/SMX, which resulted
      in 86.6% of inhibition (p = 0.048). Thus, overall, the iclaprim/SMX combination
      was more effective than TMP/SMX both in vitro and in vivo, suggesting that it
      could be an alternative therapy to the TMP/SMX combination for the treatment of
      Pneumocystis pneumonia.

PMID- 29330713
TI  - Low-field magnetic resonance imaging offers potential for measuring tibial
      component migration.
AB  - BACKGROUND: Roentgen stereophotogrammetric analysis (RSA) is used to measure
      early prosthetic migration and to predict future implant failure. RSA has several
      disadvantages, such as the need for perioperatively inserted tantalum markers.
      Therefore, this study evaluates low-field MRI as an alternative to RSA. The use
      of traditional MRI with prostheses induces disturbing metal artifacts which are
      reduced by low-field MRI. The purpose of this study is to assess the feasibility
      to use low-field (0.25 Tesla) MRI for measuring the precision of zero motion.
      This was assessed by calculating the virtual prosthetic motion of a zero-motion
      prosthetic reconstruction in multiple scanning sessions. Furthermore, the effects
      of different registration methods on these virtual motions were tested. RESULTS:
      The precision of zero motion for low-field MRI was between 0.584 mm and 1.974 mm
      for translation and 0.884 degrees  and 3.774 degrees  for rotation. The manual
      registration method seemed most accurate, with MU <= 0.13 mm (sigma <= 0.931 mm)
      for translation and MU <= 0.15 degrees  (sigma <= 1.63 degrees ) for rotation.
      CONCLUSION: Low-field MRI is not yet as precise as today's golden standard
      (marker based RSA) as reported in the literature. However, low-field MRI is
      feasible of measuring the relative position of bone and implant with comparable
      precision as obtained with marker-free RSA techniques. Of the three registration
      methods tested, manual registration was most accurate. Before starting clinical
      validation further research is necessary and should focus on improving scan
      sequences and registration algorithms.

PMID- 29330711
TI  - Boosting tendon repair: interplay of cells, growth factors and scaffold-free and
      gel-based carriers.
AB  - BACKGROUND: Tendons are dense connective tissues and critical components for the
      integrity and function of the musculoskeletal system. Tendons connect bone to
      muscle and transmit forces on which locomotion entirely depends. Due to trauma,
      overuse and age-related degeneration, many people suffer from acute or chronic
      tendon injuries. Owing to their hypovascularity and hypocellularity,
      tendinopathies remain a substantial challenge for both clinicians and
      researchers. Surgical treatment includes suture or transplantation of autograft,
      allograft or xenograft, and these serve as the most common technique for rescuing
      tendon injuries. However, the therapeutic efficacies are limited by drawbacks
      including inevitable donor site morbidity, poor graft integration, adhesion
      formations and high rates of recurrent tearing. This review summarizes the
      literature of the past 10 y concerning scaffold-free and gel-based approaches for
      treating tendon injuries, with emphasis on specific advantages of such modes of
      application, as well as the obtained results regarding in vitro and in vivo
      tenogenesis. RESULTS: The search was focused on publications released after 2006
      and 83 articles have been analysed. The main results are summarizing and
      discussing the clear advantages of scaffold-free and hydrogels carriers that can
      be functionalized with cells alone or in combination with growth factors.
      CONCLUSION: The improved understanding of tissue resident adult stem cells has
      made a significant progress in recent years as well as strategies to steer their
      fate toward tendon lineage, with the help of growth factors, have been
      identified. The field of tendon tissue engineering is exploring diverse models
      spanning from hard scaffolds to gel-based and scaffold-free approaches seeking
      easier cell delivery and integration in the site of injury. Still, the field
      needs to consider a multifactorial approach that is based on the combination and
      fine-tuning of chemical and biomechanical stimuli. Taken together, tendon tissue
      engineering has now excellent foundations and enters the period of precision and
      translation to models with clinical relevance on which better treatment options
      of tendon injuries can be shaped up.

PMID- 29330714
TI  - Evidence-Based Recommendations to Improve the Safe Use of Drugs in Patients with
      Liver Cirrhosis.
AB  - INTRODUCTION: The presence of liver cirrhosis can have a major impact on
      pharmacodynamics and pharmacokinetics, but guidance for prescribing is lacking.
      OBJECTIVE: The aim of this study is to provide an overview of evidence-based
      recommendations developed for the safe use of drugs in liver cirrhosis. METHODS:
      Recommendations were based on a systematic literature search combined with expert
      opinion from a panel of 10 experts. The safety of each drug was classified as
      safe, no additional risks known, additional risks known, unsafe, unknown or the
      safety class was dependent on the severity of liver cirrhosis (Child-Pugh
      classification). If applicable, drug-specific dosing advice was provided. All
      recommendations were implemented in clinical decision support systems and on a
      website. RESULTS: We formulated 218 recommendations for a total of 209 drugs. For
      nine drugs, two recommendations were formulated for different administration
      routes or indications. Drugs were classified as 'safe' in 29 recommendations
      (13.3%), 'no additional risks known' in 60 (27.5%), 'additional risks known' in 3
      (1.4%), and 'unsafe' in 30 (13.8%). In 57 (26.1%) of the recommendations, safety
      depended on the severity of liver cirrhosis and was 'unknown' in 39 (17.9%)
      recommendations. Large alterations in pharmacodynamics were the main reason for
      classifying a drug as 'unsafe'. For 67 drugs (31%), a dose adjustment was needed.
      CONCLUSIONS: Over 200 recommendations were developed for the safe use of drugs in
      patients with liver cirrhosis. Implementing these recommendations into clinical
      practice can possibly enhance medication safety in this vulnerable patient group.

PMID- 29330715
TI  - Case Series Analysis of New Zealand Reports of Rapid Intense Potentiation of
      Warfarin by Roxithromycin.
AB  - INTRODUCTION: We undertook an analysis of all the reports to the New Zealand
      Centre for Adverse Reactions Monitoring of a roxithromycin/warfarin interaction
      after two recent reports described intense rapid warfarin potentiation. The
      interaction was first published in 1995. Cytochrome P450 3A4 inhibition has been
      the proposed mechanism but has limited biologic plausibility. There are
      suggestions that the clinical significance of the interaction may be increased by
      severe illness, polypharmacy, renal dysfunction, older age and increased warfarin
      sensitivity. METHODS: To investigate the potentiating effect of warfarin on
      roxithromycin in this New Zealand case series, the reports were reviewed to
      identify patients at risk, compare the reporting pattern with published
      Australian data and evaluate the appropriateness of current prescribing advice.
      RESULTS: Thirty patient reports were identified. The age range was 23-88 years,
      mean 66.8, median 73.0 (standard deviation 17.7) and the international normalised
      ratios after roxithromycin commencement ranged from 3.6 to 16.7 (mean 7.6, median
      7.6, standard deviation 3.6). For eight patients with measurements on day 3,
      international normalised ratios were 4.3-16.7 (mean 10.4, median 8.8, standard
      deviation 4.4). Four patients had serious haemorrhage. Indications for
      roxithromycin were a range of respiratory tract infections. Anticoagulation was
      stable for most patients prior to acute infection. Serious infection occurred in
      54.5% (12 of 22 patients with information). Polypharmacy (five or more medicines
      daily) was used by 36.7% of patients long term, increasing acutely to 83.3%,
      including additional potentially interacting medicines. Warfarin daily dose (1.5
      13.0 mg, mean 4.4, median 4.0, standard deviation 2.2) was moderate to low. Pre
      roxithromycin international normalised ratio values ranged from 1.4 to 3.7, mean
      and median 2.5, standard deviation 0.5. A high proportion of interactions were
      observed between warfarin and roxithromycin compared with other macrolides and
      compared with cytochrome P450 3A4-related macrolide interactions. The pattern was
      similar to published Australian data. CONCLUSION: In this case series, the high
      prevalence of acute polypharmacy, including potentially interacting medicines,
      and serious infection suggests that they may have contributed to warfarin
      potentiation and increased the clinical significance of a roxithromycin/warfarin
      interaction.

PMID- 29330716
TI  - Long-Term Survival of Patients with Thin (T1) Cutaneous Melanomas: A Breslow
      Thickness Cut Point of 0.8 mm Separates Higher-Risk and Lower-Risk Tumors.
AB  - BACKGROUND: Counterintuitively, more deaths from melanoma occur among patients
      with thin (T1) primary melanomas (<= 1 mm) than among those with thick primary
      melanoma because the great majority present with T1 tumors. Therefore, it is
      important to stratify their risk as accurately as possible to guide their
      management and follow-up. This study sought to explore the relationship between
      tumor thickness and prognosis for patients with thin primary melanomas. METHODS:
      A retrospective, single-institution study investigated 6263 patients with
      cutaneous melanoma (including 2117 T1 cases) who had a minimum follow-up period
      of 10 years. RESULTS: For the entire patient cohort, the 10-year melanoma
      specific survival (MSS) rate ranged between 92% for the patients with primary
      melanomas up to 0.3 mm thick and 32% for those with melanomas thicker than 8 mm.
      When divided into 25-quantile-thickness groups there was a significant difference
      in 10-year MSS between the two consecutive groups 0.8 and 0.9 mm; the differences
      in survival were not significantly different for any other consecutive cut points
      within the less than or equal to 1 mm thickness range, indicating a biologically
      relevant difference in outcome above and below 0.8 mm. For the patients treated
      initially at the authors' institution, the 10- and 20-year MSS rates for those
      with tumors up to 0.8 mm thick were respectively 93.4 and 85.7%, and for tumors
      0.9 to 1.0 mm, the rates were respectively 81.1 and 71.4%. Only 29.3% of the T1
      patients who died of melanoma were deceased within 5 years. CONCLUSIONS: A
      naturally occurring thickness cut point of 0.8 mm predicts higher or lower risk
      for patients with thin primary cutaneous melanomas. Long-term follow-up
      assessment of patients with T1 melanoma is important because late mortality due
      to melanoma is more common than early mortality.

PMID- 29330717
TI  - Posterior Retroperitoneoscopic Resection of Extra-adrenal Paraganglioma Located
      in the Aorto-caval Space.
AB  - BACKGROUND: The posterior retroperitoneoscopic adrenalec tomy has several
      advantages compared with the transperitoneal approach such as a shorter and more
      direct route to the target organ, no breach of the intraperitoneal space, and no
      required retraction of the adjacent organs. It also is a safe procedure with a
      short learning curve.1-5 This report presents a challenging case of an extra
      adrenal paraganglioma located in the aorto-caval space and managed using the
      retroperitoneal approach. METHODS: A 39-year-old man was placed in the prone
      jackknife position, and three incisions were made in the right posterior
      abdominal wall for placement of the laparoscopic ports. The retroperitoneal space
      was entered with diathermy and blunt finger dissection, and retropneumoperitoneum
      was achieved with carbon dioxide insufflation pressure up to 18 mmHg. After
      identification of the right kidney and vessels, the tumor was meticulously
      dissected and excised with an energy device. The specimen was removed using a
      laparoscopic specimen retrieval bag, and the port sites were closed in layers.
      RESULTS: The operative time was 130 min, and the total blood loss was 30 ml. The
      tumor was diagnosed as a moderately differentiated extra-adrenal paraganglioma.
      The Von Hippel-Lindau gene mutation was detected using next-generation
      sequencing. CONCLUSIONS: The posterior retroperitoneoscopic approach is a safe,
      feasible, and effective method for excising an extra-adrenal paraganglioma even
      in the aorto-caval space. The authors suggest that this procedure is a useful
      surgical option for treatment of an aorto-caval paraganglioma for selected
      patients and by experienced surgeons.

PMID- 29330718
TI  - SPECT/CT Adds Distinct Lymph Node Basins and Influences Radiologic Findings and
      Surgical Approach for Sentinel Lymph Node Biopsy in Head and Neck Melanoma.
AB  - BACKGROUND: Planar lymphoscintigraphy (PL) has a lower detection rate of sentinel
      lymph nodes (SLNs) in head and neck melanoma compared with other sites. We
      assessed situations when single-photon emission computed tomography/computed
      tomography (SPECT/CT) identified nodes not seen by PL. We also evaluated the
      impact of SPECT/CT on surgical approach and oncologic outcomes. METHODS: Patients
      who underwent SLN biopsy (SLNB) for head and neck melanoma with PL and SPECT/CT
      between November 2011 and December 2016 were included. Surgeons and radiologists
      completed a real-time survey inquiring about the utility of SPECT/CT. Patients
      were divided into two groups: patients with nodal basins identified by both PL
      and SPECT/CT ('PL + SPECT/CT'), and patients in whom SPECT/CT identified
      additional nodal basins not seen on PL ('SPECT/CT only'). Patient demographics
      and long-term outcomes including follow-up duration, recurrence, and survival are
      described. RESULTS: In the PL + SPECT/CT group, 73 (61.9%) patients were included
      and 45 (38.1%) patients were included in the SPECT/CT-only group. SPECT/CT added
      51 basins to those seen on PL, primarily in the supraclavicular region (43.1%).
      Eighteen patients had positive node(s) in the PL + SPECT/CT group compared with
      two patients in the SPECT/CT-only group. Surgeons reported that 81% of the time,
      SPECT/CT influenced the location of incision for SLNB. CONCLUSIONS: SPECT/CT
      influences the location of incision and contributes most to identification of
      nodes in the supraclavicular region. It also detects additional SLN basins when
      compared with PL. Further studies are necessary to determine when these
      additional basins require sampling.

PMID- 29330719
TI  - Prognostic Value of Tumor-Infiltrating Lymphocyte Density Assessed Using a
      Standardized Method Based on Molecular Subtypes and Adjuvant Chemotherapy in
      Invasive Breast Cancer.
AB  - BACKGROUND: This study investigated the prognostic value of tumor-infiltrating
      lymphocyte (TIL) density as determined by molecular subtype and receipt of
      adjuvant chemotherapy in invasive breast cancer (IBC). METHODS: Stromal TIL
      densities were evaluated in 1489 IBC samples using recommendations proposed by
      the International TILs Working Group. Cases were allocated to high- and low-TIL
      density groups using a cutoff of 10%. RESULTS: Of the 1489 IBC patients, 427
      (28.7%) were assigned to the high-TIL group and 1062 (71.3%) to the low-TIL
      group. High TIL density was found to be significantly associated with large tumor
      size (p = 0.001), high histologic grade (p < 0.001), and high Ki-67 labeling
      index (p < 0.001). Triple-negative and human epidermal growth factor receptor 2
      (HER2)-positive subtypes had significantly higher TIL densities than luminal A or
      B (HER2-negative) subtypes (p < 0.001). High TIL density was significantly
      associated with prolonged disease-free survival (DFS) by univariate (p < 0.001)
      and multivariate (p < 0.001) analyses. In the low-TIL-density group, the patients
      who did not receive adjuvant chemotherapy showed better DFS (p < 0.001), but no
      such survival difference was observed in the high-TIL group (p = 0.222). For the
      patients who received adjuvant anthracycline, high-TIL density was found to be an
      independent prognostic factor of favorable DFS in the luminal B (HER2-negative; p
      = 0.003), HER2-positive (p = 0.019), and triple-negative (p = 0.017) subtypes.
      CONCLUSION: Measurements of TIL density in routine clinical practice could give
      useful prognostic information for the triple-negative, HER2-positive, and luminal
      B (HER2-negative) IBC subtypes, especially for patients administered adjuvant
      anthracycline.

PMID- 29330720
TI  - Dialysis Increases the Risk of Bladder Recurrence in Patients with Upper Tract
      Urothelial Cancer: A Population-Based Study.
AB  - BACKGROUND: The relation of dialysis to tumor recurrence in patients with upper
      tract urothelial cancer (UTUC) is unknown; however, a limited number of small
      scale studies suggest that patients with renal diseases prior to UTUC are more
      likely to exhibit bladder recurrence. We performed a population-based analysis to
      determine the effect of dialysis on bladder recurrence for patients with UTUC.
      METHODS: This retrospective cohort study included patients diagnosed with UTUC
      (2002-2007) from the Taiwan National Cancer Registry and divided them into two
      groups-dialysis and non-dialysis groups. These patients were followed up until
      bladder recurrence, death, or the end of 2010. Competing risk analyses adjusting
      covariates and death were applied to determine the relation of dialysis and
      bladder recurrence. RESULTS: Of the 5141 eligible patients, 548 (10.7%) were
      undergoing dialysis. The cumulative bladder recurrence was significantly higher
      in the dialysis group than in the non-dialysis group (29% vs. 21%, modified log
      rank p < 0.001). In the multivariable analysis, the dialysis group exhibited a
      64% increased bladder recurrence risk (cause-specific hazard ratio 1.64, 95%
      confidence interval 1.34-2.01, p < 0.001), which was confirmed using
      stratification and propensity score weighting methods. The other prognostic
      factors for bladder recurrence were sex, diabetes, cardiac disorder, Charlson
      Comorbidity Index, and tumor grade. CONCLUSIONS: Despite unknown reasons,
      approximately one-tenth of patients with UTUC have experienced dialysis
      treatment. Patients undergoing dialysis have a higher risk of bladder recurrence.
      Various treatment and screening strategies should be developed for dialysis and
      non-dialysis patients.

PMID- 29330721
TI  - Transcriptomic analysis and discovery of genes in the response of Arachis
      hypogaea to drought stress.
AB  - The peanut (Arachis hypogaea) is an important crop species that is threatened by
      drought stress. The genome sequences of peanut, which was officially released in
      2016, may help explain the molecular mechanisms that underlie drought tolerance
      in this species. We report here a gene expression profiling of A. hypogaea to
      gain a global view of its drought resistance. Using whole-transcriptome
      sequencing, we analysed differential gene expression in response to drought
      stress in the drought-resistant peanut cultivar J11. Pooled samples obtained at
      6, 12, 18, 24, and 48 h were compared with control samples at 0 h. In total,
      51,554 genes were found, including 49,289 known genes and 2265 unknown genes. We
      identified 224 differentially expressed transcription factors, 296,335 SNPs and
      28,391 InDELs. In addition, we detected significant differences in the gene
      expression profiles of the treatment and control groups. After comparing the two
      groups, 4648 genes were identified. An in-depth analysis of the data revealed
      that a large number of genes were associated with drought stress, including
      transcription factors and genes involved in photosynthesis-antenna proteins,
      carbon metabolism and the citrate cycle. The results of this study provide
      insights into the diverse mechanisms that underlie the successful establishment
      of drought resistance in the peanut, thereby facilitating the identification of
      important genes in the peanut related to drought management. Transcriptome
      analysis based on RNA-Seq is a powerful approach for gene discovery and molecular
      marker development for this species.

PMID- 29330722
TI  - Location of low copy genes in chromosomes of Brachiaria spp.
AB  - Repetitive DNA sequences have been widely used in cytogenetic analyses. The use
      of gene sequences with a low-copy-number, however, is little explored especially
      in plants. To date, the karyotype details in Brachiaria spp. are limited to the
      location of rDNA sites. The challenge lies in developing new probes based on
      incomplete sequencing data for the genus or complete sequencing of related
      species, since there are no model species with a sequenced genome in Brachiaria
      spp. The present study aimed at the physical location of conserved genes in
      chromosomes of Brachiaria ruziziensis, Brachiaria brizantha, and Brachiaria
      decumbens using RNAseq data, as well as sequences of Setaria italica and Sorghum
      bicolor through the fluorescent in situ hybridization technique. Five out of
      approximately 90 selected sequences generated clusters in the chromosomes of the
      species of Brachiaria studied. We identified genes in synteny with 5S and 45S
      rDNA sites, which contributed to the identification of chromosome pairs carrying
      these genes. In some cases, the species of Brachiaria evaluated had syntenic
      segments conserved across the chromosomes. The use of genomic sequencing data is
      essential for the enhancement of cytogenetic analyses.

PMID- 29330723
TI  - Association Between the Incidence of Pancreatic Fistula After
      Pancreaticoduodenectomy and the Degree of Pancreatic Fibrosis.
AB  - OBJECTIVE: The objective of this study is to investigate the association between
      the incidence of pancreatic fistula after pancreaticoduodenectomy (PD) and the
      degree of pancreatic fibrosis. METHOD: Between January 2013 and December 2016,
      the analysis of the clinical data of 529 cases of pancreaticoduodenectomy
      patients of our hospital was performed in a retrospective fashion. The univariate
      analysis and multivariate analysis were done using the Pearson chi-squared test
      and binary logistic regression analysis model; correlations were analyzed by
      Spearman rank correlation analysis. The value of the degree of pancreatic
      fibrosis to predict the incidence of pancreatic fistula after
      pancreaticoduodenectomy was evaluated by the area under the receiver operating
      characteristic (ROC) curve. RESULTS: The total incidence of pancreatic fistula
      after pancreaticoduodenectomy was 28.5% (151/529). Univariate analysis and
      multivariate analysis showed that BMI >= 25 kg/m2, pancreatic duct size <= 3 mm,
      pancreatic CT value< 30, the soft texture of the pancreas (judged during the
      operation), and the percent of fibrosis of pancreatic lobule <= 25% are
      prognostic factors of pancreatic fistula after pancreaticoduodenectomy (P <
      0.05); the pancreatic CT value and the percent of fibrosis of pancreatic lobule
      in pancreatic fistula group were both lower than those in non-pancreatic fistula
      group (P < 0.05). Results indicated that there is a negative correlation between
      the severity of pancreatic fistula and the pancreatic CT value or the percent of
      fibrosis of pancreatic lobule (r = - 0.297, - 0.342, respectively). The areas
      under the ROC curve of the percent of fibrosis of pancreatic lobule and the
      pancreatic CT value were 0.756 and 0.728, respectively. CONCLUSION: The degree of
      pancreatic fibrosis is a prognostic factor which can influence the pancreatic
      texture and the incidence of pancreatic fistula after pancreaticoduodenectomy.
      The pancreatic CT value can be used as a quantitative index of the degree of
      pancreatic fibrosis to predict the incidence of pancreatic fistula after
      pancreaticoduodenectomy.

PMID- 29330725
TI  - Cytologic Diagnosis of Biliary Strictures: FISH or Cut the Sensitivity Rate?

PMID- 29330724
TI  - A Novel Nomogram for Predicting Postsurgical Intra-abdominal Infection in Gastric
      Cancer Patients: a Prospective Study.
AB  - BACKGROUND: This study aimed to determine the relationship between intra
      abdominal infection (IAI) and sarcopenia prospectively and to construct a
      nomogram to identify patients at a high risk of IAI. METHODS: We conducted a
      prospective study of 682 consecutive patients with gastric cancer who underwent
      radical gastrectomy. The sarcopenia elements, including lumbar skeletal muscle
      index, handgrip strength, and gait speed, were measured before surgery. Factors
      contributing to IAI were determined through univariate and multivariate analysis.
      A nomogram consisting of the independent risk factors was constructed to quantify
      the individual risk of IAI. RESULTS: Of the 682 patients enrolled in this study,
      132 patients were diagnosed with sarcopenia and 61 were diagnosed with IAI.
      Logistic analysis revealed that sarcopenia, tumor size, pathological type, and
      multivisceral resection were independent prognostic factors for IAI. The nomogram
      model for IAI was able to reliably quantify the risk of IAI with a strong
      optimism-adjusted discrimination (concordance index, 0.736). CONCLUSIONS:
      Sarcopenia is an independent predictor of IAI. Our nomogram was a simple and
      practical instrument to quantify the individual risk of IAI and could be used to
      identify patients at a high risk.

PMID- 29330727
TI  - Gastroenterology Fellowship Match: An Inside Look.

PMID- 29330726
TI  - Ultra-Deep Genomic Sequencing of HCV NS5A Resistance-Associated Substitutions in
      HCV/HIV Coinfected Patients.
AB  - BACKGROUND AND AIMS: The prevalence of naturally occurring HCV-NS5A resistance
      associated substitutions (RAS) to DAA drugs might affect the response to
      treatment in HCV/HIV coinfected subjects. There are limited data on the frequency
      of HCV-NS5A naturally occurring drug-RAS at baseline in HCV/HIV coinfected
      patients when ultra-deep sequencing methodologies are applied. METHODS: HCV-NS5A
      RAS were evaluated among 25 subjects in each group. Patients were matched by age,
      gender, and hepatic fibrosis stage category to control for selection bias.
      RESULTS: Within subtype 1a, RAS were observed in 28% of HCV monoinfected and 48%
      of HCV/HIV coinfected subjects. More patients in the HCV/HIV coinfected group had
      clinically relevant mutations to DAA directed at NS5A. CONCLUSION: While the
      clinical significance of this observation may be limited in highly drug adherent
      populations, some HCV/HIV coinfected persons may be at greater risk of viral
      resistance if suboptimal dosing occurs.

PMID- 29330729
TI  - Revenge of the NERDs: Cadherin Fragments Differentiate Functional Heartburn from
      Non-erosive Reflux Disease.

PMID- 29330728
TI  - Analysis of Plasma Tenascin-C in Post-HCV Cirrhosis: A Prospective Study.
AB  - BACKGROUND AND AIM: Hepatitis C virus (HCV)-related cirrhosis, one of the most
      common etiologies of liver cirrhosis in the Western world, is a risk factor for
      hepatocellular carcinoma. To confirm and improve current effectiveness of
      screening and prognosis of patients with established cirrhosis, a credible,
      simple plasma biomarker is needed. Hepatic stellate cell activation, a pivotal
      event in cirrhosis development, results in increased secretion of extracellular
      matrix proteins, including tenascin-C (TnC). Herein, we tested TnC as a simple
      biomarker to identify cirrhotic patients with active HCV infection from those
      with HCV eradication. METHODS: A prospective study of subjects with HCV-related
      cirrhosis, stratified into two groups, HCV or virologic cure, was conducted.
      Plasma TnC expression was measured by ELISA and Western blots. TnC values were
      correlated with markers of liver injury and ROC analyses performed between
      groups. RESULTS: The HCV cirrhotic cohort, consisting mostly of men (56%),
      Caucasians (76%), and genotype 1a or 1b (84%), was compared to healthy controls
      (HCs). Plasma TnC was significantly higher in HCV cirrhotic patients with active
      infection compared to HCs (P < 0.0001) and virologic cure (P < 0.0001). TnC
      concentrations in virologic cure subjects were not statistically different from
      HCs. TnC levels correlated with AST, platelets, MELD, APRI, FIB-4, and Child-Pugh
      score. TnC and AST together were significantly better indicators of cirrhosis in
      patients with active HCV infection than other markers tested. CONCLUSIONS: TnC
      and AST provided the best model for discriminating HCV cirrhotics with active
      infection from HC and virologic cure cohorts over current liver injury markers,
      suggesting TnC as a potential indicator of ongoing hepatic injury and
      inflammation.

PMID- 29330730
TI  - Scaffold-free tissue engineering for injured joint surface restoration.
AB  - Articular cartilage does not heal spontaneously due to its limited healing
      capacity, and thus effective treatments for cartilage injuries has remained
      challenging. Since the first report by Brittberg et al. in 1994, autologous
      chondrocyte implantation (ACI) has been introduced into the clinic. Recently, as
      an alternative for chondrocyte-based therapy, mesenchymal stem cell (MSC)-based
      therapy has received considerable research attention because of the relative ease
      in handling for tissue harvest, and subsequent cell expansion and
      differentiation. In this review, we discuss the latest developments regarding
      stem cell-based therapies for cartilage repair, with special focus on recent
      scaffold-free approaches.

PMID- 29330731
TI  - Human Plant Exposures Reported to a Regional (Southwestern) Poison Control Center
      Over 8 Years.
AB  - BACKGROUND: There is little published data about human plant exposures reported
      to US poison control centers (PCCs). METHODS: A retrospective chart review of all
      reported plant exposures to a single regional PCC between January 1, 2003 and
      December 31, 2010 was done to understand better the characteristics of plant
      exposure cases. Specific generic plant codes were used to identify cases.
      Recorded variables included patient demographics, plant involved, exposure
      variables, symptoms, management site, treatments, and outcome. Univariate and
      multivariate regression was used to identify outcome predictors. RESULTS: A total
      of 6492 charts met inclusion criteria. The average age was 16.6 years (2 months
      94 years); 52.4% were male. The most common exposure reason was unintentional
      (98%), and the majority (92.4%) occurred at the patient's home. Ingestions
      (58.3%) and dermal exposures (34.3%) accounted for most cases. Cactus (27.5%),
      oleander (12.5%), Lantana (5.7%), and Bougainvillea (3.8%) were most commonly
      involved. Symptoms developed in 47.1% of patients, and were more likely to occur
      following Datura (66.7%), and Morning Glory or Milkweed (25% each) exposures.
      Almost 94% of patients were managed onsite (home) and only 5.2% involved
      evaluation in a health care facility (HCF). Only 37 (0.6%) patients required
      hospital admission, and 2.9% of cases resulted in more than minimal effects.
      Exposures resulting in more than minimal clinical effects were predicted by
      several variables: abnormal vital signs (OR = 35.62), abnormal labs (OR = 14.87),
      and management at a HCF (OR = 7.37). Hospital admissions were increased for
      patients already at a HCF (OR = 54.01), abnormal vital signs (OR = 23.28), and
      intentional exposures (OR = 14.7). CONCLUSION: Plant exposures reported to our
      poison control center were typically unintentional ingestions occurring at home.
      Most patients were managed onsite and few developed significant symptoms.

PMID- 29330732
TI  - Touching the Spirit: Re-enchanting the Person in the Body.
AB  - In this essay, we argue that touch constitutes a sacred connection between the
      patient and practitioner. When touch is avoided or overlooked, the enigmatic
      inner workings of the body are ignored as those aspects of the body that can be
      quantified and ultimately controlled are emphasized. In utilizing touch as a
      fundamental way of opening up space for the sacred, the practitioner affirms the
      humanity for both the patient and herself. Only by returning to the senses can
      practitioners resist the dehumanizing effects of machinery and re-enchant the
      health-care profession in caring for persons they have sworn to serve.

PMID- 29330734
TI  - How does School Experience Relate to Adolescent Identity Formation Over Time?
      Cross-Lagged Associations between School Engagement, School Burnout and Identity
      Processing Styles.
AB  - The existing research findings still do not provide a clear understanding of the
      links between adolescent school experience and their identity formation. To
      address this gap, we analyzed the dynamic links between adolescent school
      experiences and identity formation by exploring the cross-lagged associations
      between school engagement, school burnout and identity processing styles
      (information-oriented, normative and diffuse-avoidant) over a 2-year period
      during middle-to-late adolescence. The sample of this school-based study included
      916 adolescents (51.4% females) in the 9th to 12th grades from diverse socio
      economic and family backgrounds. The results from the cross-lagged analyses with
      three time points revealed that (a) school engagement positively predicted
      information-oriented identity processing over a 2-year period; (b) school burnout
      positively predicted the reliance on normative and diffuse-avoidant identity
      styles across the three measurements; (c) the effects were stable over the three
      time points and across different gender, grade, and socio-economic status groups.
      The unidirectional effects identified in our study support the general prediction
      that active engagement in learning at school can serve as a resource for
      adolescent identity formation, while school burnout, in contrast, can hinder the
      formation of adolescent identity. This points to the importance of taking
      developmental identity-related needs of adolescents into account when planning
      the school curriculum.

PMID- 29330736
TI  - Study on the Multi-level Resistance-Switching Memory and Memory-State-Dependent
      Photovoltage in Pt/Nd:SrTiO3 Junctions.
AB  - Pt/Nd:SrTiO3 (STO)/In devices were fabricated by depositing Schottky-contact Pt
      and Ohmic-contact In electrodes on a single crystal STO with Nd doping. The
      Pt/Nd:STO/In devices show multi-level resistance-switching (RS) memory and memory
      state-dependent photovoltage (PV) effects, which can be controlled by the applied
      pulse width or magnitude. Both the RS and PV are related to the bias-induced
      modulation of the interface barrier, both in height and width, at the Pt/Nd:STO
      interface. The results establish a strong connection between the RS/PV effects
      and the modulation of the Nd:STO interface triggered by applied electric field
      and provide a new route by using an open-circuit voltage for non-destructively
      sensing multiple non-volatile memory states.

PMID- 29330733
TI  - Intergenerational Continuity in Depression: The Importance of Time-Varying
      Effects, Maternal Co-morbid Health Risk Behaviors and Child's Gender.
AB  - Intergenerational continuity in depressive symptoms is well established between
      mother and child, but there are still important facets of this relationship that
      are underexplored. We examine intergenerational continuity in depressive symptoms
      between mother-child dyads as a flexible function of child age and account for
      the potential moderating role of maternal co-morbid health risk behaviors. Using
      prospective, self-report data collected yearly from 413 mother-child dyads (210
      mother-son dyads and 203 mother-daughter dyads) between child ages 12-17, the
      results indicate that the effect of maternal depressive symptoms on daughters'
      depressive symptoms steadily increases throughout adolescence whereas the effect
      of maternal depressive symptoms on sons' depressive symptoms is relatively small,
      stable, and non-significant during mid-adolescence before increasing in effect in
      later adolescence. A positive interactive effect between maternal depressive
      symptoms and intimate partner violence is observed for sons and maternal
      depressive symptoms and substance use for daughters. A negative interactive
      effect of maternal depressive symptoms and substance use is observed among sons.
      Overall, this study identifies particular subgroups for whom intervention
      programming is most beneficial and suggests targeting health risk behaviors of
      mothers to lessen the impact of maternal depressive symptoms on offspring.

PMID- 29330737
TI  - Letter to the editor.

PMID- 29330738
TI  - A video review of multiple concussion signs in National Rugby League match play.
AB  - BACKGROUND: Video review has been introduced in many professional sports
      worldwide to help recognize concussions. However, to date, there has been very
      little research on the accuracy of using video analysis to identify signs of
      concussion and the various combinations of observed signs. METHODS: The objective
      of the study is to determine the accuracy of combinations of clinical signs of
      concussion identified using video analysis to identify concussions in the
      National Rugby League (NRL). Incidences of players using of the concussion
      interchange rule (CIR) (n = 156), including those where athletes were diagnosed
      with a concussion (n = 60), were used to calculate sensitivity and specificity of
      various combinations of concussion signs (unresponsiveness, slow to get up,
      clutching/shaking head, gait ataxia, vacant stare, and apparent seizure) and
      their independent association with an eventual diagnosis of concussion. RESULTS:
      Using video analysis, players who were diagnosed with a concussion showed a
      significantly greater total number of signs at the time of injury (mean = 3.4, SD
      = 1.3) than those who were removed from play but not diagnosed with a concussion
      (mean = 3.0, SD = 0.9 signs; p = .046). Players who did not return to play during
      the same game demonstrated a significantly greater number of total signs than
      those who did return to play in the same game following CIR activation (mean =
      3.4, SD = 1.2 versus mean = 2.9, SD = 0.9; p = 0.002). The most common
      combination of signs that was observed was clutching/shaking the head and
      slowness in getting up (17.3%). The sensitivity of the total number of signs
      observed decreased as the number of signs increased (range = 0.13-0.62), while
      the specificity increased as more signs were observed (range = 0.29-0.90). Most
      of the combinations of different observed signs at the time of potential injury
      were highly specific (> 0.80), but not sensitive to an eventual diagnosis of
      concussion. When considering all potential predictor variables in a logistic
      regression model, anticipating the oncoming collision (OR = 3.92, 95% CI = 1.28
      12.03), fewer number of defenders involved in the tackle (OR = 0.58, 95% CI =
      0.36-0.92), and the presence of a blank or vacant stare (OR = 2.97, 95% CI = 1.26
      7.01) were each significantly associated with concussion diagnoses. CONCLUSIONS:
      The use of video review in the NRL is challenging, but being aware of the
      combinations of possible concussion signs and the likelihood that various
      presentations result in a concussion diagnosis can provide a useful addition to
      sideline concussion identification and removal from play decisions.

PMID- 29330739
TI  - Patterns and outcomes of prescribing venous thromboembolism prophylaxis in
      hospitalized older adults: a retrospective cohort study.
AB  - Venous thromboembolism (VTE) is a major cause of morbidity and mortality in the
      United States. Hospitalized, medically ill older adults have increased risk;
      despite guidelines, data suggest suboptimal pharmacologic prophylaxis rates.
      Factors influencing provider prescribing non-compliance are unclear. We aimed to
      describe VTE prophylaxis practices and identify risk factors for, and outcomes
      of, prescribing non-compliance. A retrospective study was conducted of
      hospitalized adults aged >= 75 years, admitted to the medicine service of a large
      academic tertiary center from May 1, 2014 to June 30, 2015. The primary outcome
      was non-compliance, defined as the absence of an order for VTE prophylaxis for
      the duration of hospitalization or an interruption of prophylaxis exceeding 24 h.
      Secondary measures included in-hospital mortality, length of stay (LOS), and 30
      day readmissions. Of 3751 patients (mean age 84.7 years), 97.6% of charts had
      prophylaxis orders; 11.0% showed non-compliance. Pharmacologic prophylaxis was
      prescribed in 83.3% of patients and mechanical prophylaxis alone in 14.3%.
      Factors associated with non-compliance included: higher body mass index (BMI) (p
      = 0.04), myocardial infarction (p = 0.01), congestive heart failure (p = 0.001),
      metastatic tumor (p = 0.01). Low mobility was not significantly associated with
      compliance. Subcutaneous unfractionated heparin was associated with compliance (p
      < 0.0001); warfarin (p < 0.0001), heparin infusion (p < 0.0001) and low-molecular
      weight heparin (p < 0.0001) with non-compliance. Non-compliance was associated
      with increased mortality (p = 0.01), LOS (p < 0.0001), readmissions (p = 0.0004).
      Known VTE risk factors (mobility, BMI, comorbidities) were not associated with
      prescriber compliance patterns. Integrating risk assessment models into provider
      practice may improve compliance.

PMID- 29330740
TI  - 3D reconstruction of dynamic liquid film shape by optical grid deflection method.
AB  - In this paper, we describe the optical grid deflection method used to reconstruct
      the 3D profile of liquid films deposited by a receding liquid meniscus. This
      technique uses the refractive properties of the film surface and is suitable for
      liquid thickness from several microns to millimeter. This method works well for
      strong interface slopes and changing in time film shape; it applies when the
      substrate and fluid media are transparent. The refraction is assumed to be
      locally unidirectional. The method is particularly appropriate to follow the
      evolution of parameters such as dynamic contact angle, triple liquid-gas-solid
      contact line velocity or dewetting ridge thickness.

PMID- 29330741
TI  - Coronary artery aneurysm regression after Kawasaki disease and associated risk
      factors: a 3-year follow-up study in East China.
AB  - Kawasaki disease (KD) is the leading cause of acquired heart disease due to its
      complicated coronary artery lesions. Up to now, few studies were focused on the
      status of persistent coronary artery aneurysms (CAA) in KD patients. The present
      study was designed to identify the coronary artery outcomes and seek the risk
      factors associated with the regression of CAA in KD patients. One hundred and
      twenty KD patients with CAA hospitalized in Children's Hospital of Soochow
      University from Jan 2008 to Dec 2013 were prospectively studied by a 3-year
      follow-up. Data regarding demographic, clinical, laboratory, and
      echocardiographic characteristics were documented and further analyzed. It was
      estimated that 39.2% of the patients had complete regression of CAA within 4
      weeks, 59.2% within 8 weeks, and 70.0% within 16 weeks. No fatal cardiac events
      occurred. We found patients who aged <= 1 year, received initial intravenous
      immunoglobulin (IVIG) treatment after the 10th day of illness, and IVIG non
      responders were associated with the regression of persistent CAA. The relative
      risks were 1.55, 1.87, and 1.88, respectively. Age, initial IVIG treatment, and
      IVIG response were risk factors of persistent CAA, and more attention should be
      paid on these patients.

PMID- 29330742
TI  - Henoch-Schonlein purpura nephritis: initial risk factors and outcomes in a Latin
      American tertiary center.
AB  - The objective of this study was to evaluate prevalence, initial risk factors, and
      outcomes in Henoch-Schonlein purpura nephritis (HSPN) patients in Latin America.
      Two hundred ninety-six patients (validated EULAR/PRINTO/PRES HSP criteria) were
      assessed by demographic data, clinical/laboratorial involvements, and treatments
      in the first 3 months after diagnosis. They were followed-up in a Latin American
      tertiary center and were divided in two groups: with and without nephritis.
      Persistent non-nephrotic proteinuria, nephrotic proteinuria, and acute/chronic
      kidney injury were also systematically evaluated at 1, 5, 10, and 15 years after
      diagnosis. HSPN was evidenced in 139/296 (47%) in the first 3 months. The median
      age at diagnosis was significantly higher in HSPN patients compared without renal
      involvement [6.6 (1.5-17.7) vs. 5.7 (0.9-13.5) years, p = 0.022]. The frequencies
      of persistent purpura (31 vs. 10%, p < 0.0001), recurrent abdominal pain (16 vs.
      7%, p = 0.011), gastrointestinal bleeding (25 vs. 10%, p < 0.0001), and
      corticosteroid use (54 vs. 41%, p = 0.023) were significantly higher in the
      former group. Logistic regression demonstrated that the independent variables
      associated with HSNP were persistent purpura (OR = 3.601; 95% CI (1.605-8.079); p
      = 0.002) and gastrointestinal bleeding (OR = 2.991; 95% CI (1.245-7.183); p =
      0.014). Further analysis of patients without HSPN in the first 3 months revealed
      that 29/118 (25%) had persistent non-nephrotic proteinuria and/or hematuria in 1
      year, 19/61 (31%) in 5 years, 6/17 (35%) in 10 years and 4/6 (67%) in 15 years
      after diagnosis. None of them had chronic kidney injury or were submitted to
      renal replacement therapy. The present study observed HSPN in almost one half of
      patients in the first months of disease, and HSPN was associated with persistent
      purpura and gastrointestinal bleeding. One fourth of patients had nephritis only
      evidenced during follow-up without severe renal manifestations.

PMID- 29330743
TI  - Acute downregulation of miR-155 leads to a reduced collagen synthesis through
      attenuating macrophages inflammatory factor secretion by targeting SHIP1.
AB  - Fibrosis, tightly associated with fibroblasts collagen synthesis, is related
      closely with inflammatory response. Our previously study found that acute
      downregulation of miR-155 at wound sites leads to a reduced fibrosis, however its
      particular mechanism is unclear. Herein, we aimed to explore the mechanism of miR
      155 in reducing fibrosis. We first found that down-regulation of miR-155
      inhibited macrophages transforming growth factor-beta1 (TGF-beta1) and IL-1beta
      secretion. Next, we found that co-cultured with macrophages increased the
      proliferation and collagen synthesis of fibroblasts, and downregulation of miR
      155 in macrophages could effectively attenuate the accelerative effects. We
      further identified SH2 domain containing inositol-5-phosphatase 1 (SHIP1) as a
      direct target of miR-155 in macrophages, and the expression of SHIP1 was
      negatively correlated with the level of miR-155. We further confirmed that
      PI3K/Akt pathway was involved in this process. Last, we found that downregulation
      of miR-155 leads to a reduced fibrosis in sever burn rat. Taken together, these
      results indicate that down-regulation of miR-155 leads to a reduced fibroblasts
      proliferation and collagen synthesis through attenuating macrophages TGF-beta1
      and IL-1beta secretion by targeting SHIP1 via PI3K/Akt pathway, suggesting its
      potential therapeutic effects on the treatment of skin fibrosis.

PMID- 29330744
TI  - c-Fos downregulation positively regulates EphA5 expression in a congenital
      hypothyroidism rat model.
AB  - The EphA5 receptor is well established as an axon guidance molecule during neural
      system development and plays an important role in dendritic spine formation and
      synaptogenesis. Our previous study has showed that EphA5 is decreased in the
      developing brain of congenital hypothyroidism (CH) and the EphA5 promoter
      methylation modification participates in its decrease. c-Fos, a well-kown
      transcription factor, has been considered in association with brain development.
      Bioinformatics analysis showed that the EphA5 promoter region contained five
      putative c-fos binding sites. The chromatin immunoprecipitation (ChIP) assays
      were used to assess the direct binding of c-fos to the EphA5 promoter.
      Furthermore, dual-luciferase assays showed that these three c-fos protein binding
      sites were positive regulatory elements for EphA5 expression in PC12 cells.
      Moreover, We verified c-fos positively regulation for EphA5 expression in CH
      model. Q-PCR and Western blot showed that c-fos overexpression could upregulate
      EphA5 expression in hippocampal neurons of rats with CH. Our results suggest that
      c-fos positively regulates EphA5 expression in CH rat model.

PMID- 29330745
TI  - [Treatment of rotational malalignment of the lower leg].
AB  - BACKGROUND: Rotational malalignment after intramedullary nailing of tibial shaft
      fractures is not uncommon. In-toeing and out-toeing conditions in children are
      often the reason for orthopedic and traumatological medical consultation.
      OBJECTIVE: Evaluation of diagnostic modalities and therapeutic options for
      rotational malalignment in relationship to the patient's age. Surgical
      indications and efficacy of specific surgical techniques. MATERIAL AND METHODS:
      Systematic literature search in the German Institute for Medical Documentation
      and Information (DIMDI) and MEDLINE and evaluation of the currently published
      articles. RESULTS: In adults computed tomography (CT) scanning is the gold
      standard for measuring the rotational alignment of the lower leg. To avoid
      exposure to ionizing radiation, magnetic resonance imaging (MRI) is currently the
      preferred modality in children and adolescents. The indications for corrective
      osteotomy are dependent on the functional complaints as well as the rotation
      angle measured by CT or MRI. Presently, there is no published study which
      demonstrates a correlation between rotation of the lower leg and the development
      of arthrosis in the knee or ankle joint. When a rotational osteotomy above the
      tibial tubercle is performed, correction of the rotation and the distance between
      the tibial tuberosity and the trochlear groove (TT-TG) and therefore
      patellofemoral imbalance can be effectively treated. Treatment of rotational
      malalignment after tibial shaft fractures is performed by diaphyseal osteotomy
      with intramedullary nail stabilization. In children, supramalleolar rotational
      osteotomy with subsequent locking plate osteosynthesis or stabilization using
      external fixation is performed for torsion correction. CONCLUSION: If there is a
      suspicion of rotational malalignment in the lower leg, a CT scan can be performed
      in adults and MRI in children and adolescents. Surgical indications for
      corrective osteotomy are dependent on functional complaints as well as the CT and
      MRI measurements. The CT and MRI reference values are only published according to
      the method of Waidelich et al. and Jend et al.

PMID- 29330747
TI  - Recent Advances in Screening for Barrett's Esophagus.
AB  - OPINION STATEMENT: PURPOSE OF REVIEW: There is a pressing need for effective
      strategies to halt the increase in both the incidence and mortality of esophageal
      adenocarcinoma (EAC). Screening for Barrett's esophagus, which is the only known
      precursor of EAC, remains a ripe area for research, particularly with regard to
      identifying the target population, screening tools, and management of screen
      detected populations. This review aims to explore in depth the rationale for
      screening for Barrett's esophagus, recent biotechnological advances which may
      have the potential of making screening feasible, and also highlight the
      challenges which will have to be overcome in order make screening for BE a
      realistic prospect. RECENT FINDINGS: Imaging techniques such as portable
      transnasal endoscopy have the advantage of providing an immediate diagnosis of
      Barrett's esophagus as well as other significant pathologies such as reflux
      esophagitis and cancer; however, larger studies in non-enriched community
      screening populations are required to evaluate their feasibility. The capsule
      sponge is a cell-sampling device coupled with a biomarker, which has been most
      extensively evaluated with very promising results as regards feasibility,
      acceptability, accuracy, and cost-effectiveness. Its effectiveness in increasing
      the detection of Barrett's esophagus in primary care is currently being
      evaluated. Several Barrett's esophagus risk prediction scores have been developed
      with variable degrees of accuracy. Several minimally and non-invasive screening
      techniques have been studied including imaging and cell-sampling devices.
      Barrett's risk assessment models need to be further validated in independent,
      relevant screening populations with clear cut-offs for recommending screening to
      be defined.

PMID- 29330748
TI  - Surgery in elderly patients with intracranial meningioma: neuropsychological
      functioning during a long term follow-up.
AB  - Surgical treatment of elderly patients with meningioma is has proved to be safe,
      especially when patients are selected using dedicated surgical scores. These
      scores take into account tumor size, edema, location and patient's co
      morbidities. Neuropsychological functioning (NPF) of this kind of patients has
      been poorly studied in literature and it is not taken into account by these
      scores. Aim of our study was to describe the long-term outcome in terms of NPF of
      elderly patients undergoing surgery. Patients older than 70 years of age affected
      by intracranial meningioma and selected with the Clinical-Radiological Grading
      Score were included in our study. Neuropsychological testing was performed using
      a dedicated battery of tests before surgery, 3 and 12 months after surgery.
      Clinical, neurological and radiological outcomes were studied as well. Forty-one
      patients with a median age of 74 years were included in this study.
      Preoperatively only 1/41 patients showed a normal NPF with all tests scoring
      normally. Four out of 39 patients showed a complete neuropsychological recovery
      after 3 months; while 10/37 patients had a complete recovery after 12 months. NPF
      showed a trend of progressive improvement after surgery. Our study is the first
      experience reported in literature describing a long term follow-up in elderly
      patients after surgery for intracranial meningioma. In our series, surgery
      determined an improvement of NPF over time; especially with a low complication
      rate related to the selection of patients obtained through the CRGS. Further
      studies need to be performed in order to understand how brain edema, tumor size,
      volume and tumor location affect NPF in both short and long term.

PMID- 29330749
TI  - Toxicity and efficacy of lomustine and bevacizumab in recurrent glioblastoma
      patients.
AB  - The combination of lomustine and bevacizumab is a commonly used salvage treatment
      for recurrent glioblastoma (GBM). We investigated the toxicity and efficacy of
      lomustine plus bevacizumab (lom-bev) in a community-based patient cohort and made
      a comparison to another frequently used combination therapy consisting of
      irinotecan plus bevacizumab (iri-bev). Seventy patients with recurrent GBM were
      treated with lomustine 90 mg/m2 every 6 weeks and bevacizumab 10 mg/kg every 2
      weeks. Toxicity was registered and compared to the toxicity observed in 219
      recurrent GBM patients who had previously been treated with irinotecan 125 mg/m2
      and bevacizumab 10 mg/kg every 2 weeks. The response rate was 37.1% for lom-bev
      and 30.1% for iri-bev. Median progression-free survival (PFS) was 23 weeks for
      lom-bev and 21 weeks for iri-bev (p = 0.9). Overall survival (OS) was 37 weeks
      for lom-bev and 32 weeks for iri-bev (p = 0.5). Lom-bev caused a significantly
      higher frequency of thrombocytopenia (11.4% grade 3-4) compared to iri-bev (3.5%
      grade 3-4). Iri-bev patients had more gastrointestinal toxicity with regard to
      nausea, vomiting, diarrhea, constipation and stomatitis. Within the limitations
      of the study lom-bev is a well-tolerated treatment for recurrent GBM, although
      hematological toxicity may be a dose limiting factor. No significant differences
      between lom-bev and iri-bev were observed with regard to PFS or OS. The
      differences in toxicity profiles between lom-bev and iri-bev could guide
      treatment decision in recurrent GBM therapy as efficacy is equal and no
      predictive factors for efficacy exist.

PMID- 29330746
TI  - Risk-stratified therapy for children with FLT3-ITD-positive acute myeloid
      leukemia: results from the JPLSG AML-05 study.
AB  - Acute myeloid leukemia harboring internal tandem duplication of FMS-like tyrosine
      kinase 3 (AMLFLT3-ITD) is associated with poor prognosis. We evaluated the
      results of the AML-05 study, in which all AMLFLT3-ITD patients were assigned to
      receive hematopoietic stem cell transplantation (HSCT) in the first remission
      (1CR). We also investigated the effects of additional genetic alterations on FLT3
      ITD. The 5-year overall survival (OS) and event-free survival (EFS) rates among
      the 47 AMLFLT3-ITD patients were 42.2 and 36.8%, respectively. The 5-year disease
      free survival rate among 29 patients without induction failure was 58.4%. We
      defined the allelic ratio (AR) of FLT3-ITD to WT > 0.7 as high. Significant
      differences were found in OS (AR-high, 20% vs. AR-low, 66%, p < 0.001) and EFS
      (13 vs. 50%, p = 0.004). All five patients with concurrent NPM1 mutations
      survived, while seven of eight patients who expressed the NUP98-NSD1 chimera
      failed to achieve 1CR and died. Multivariate analysis revealed that AR > 0.7 and
      expression of the NUP98-NSD1 chimera strongly impacted OS and EFS. Although all
      the AMLFLT3-ITD patients received HSCT at 1CR, the treatment outcome of AMLFLT3
      ITD patients did not improve compared with those in a previous study.
      Heterogeneity was observed among AMLFLT3-ITD patients.

PMID- 29330750
TI  - Immunologic and gene expression profiles of spontaneous canine
      oligodendrogliomas.
AB  - Malignant glioma (MG), the most common primary brain tumor in adults, is
      extremely aggressive and uniformly fatal. Several treatment strategies have shown
      significant preclinical promise in murine models of glioma; however, none have
      produced meaningful clinical responses in human patients. We hypothesize that
      introduction of an additional preclinical animal model better approximating the
      complexity of human MG, particularly in interactions with host immune responses,
      will bridge the existing gap between these two stages of testing. Here, we
      characterize the immunologic landscape and gene expression profiles of
      spontaneous canine glioma and evaluate its potential for serving as such a
      translational model. RNA in situ hybridization, flowcytometry, and RNA sequencing
      were used to evaluate immune cell presence and gene expression in healthy and
      glioma-bearing canines. Similar to human MGs, canine gliomas demonstrated
      increased intratumoral immune cell infiltration (CD4+, CD8+ and CD4+Foxp3+ T
      cells). The peripheral blood of glioma-bearing dogs also contained a relatively
      greater proportion of CD4+Foxp3+ regulatory T cells and plasmacytoid dendritic
      cells. Tumors were strongly positive for PD-L1 expression and glioma-bearing
      animals also possessed a greater proportion of immune cells expressing the immune
      checkpoint receptors CTLA-4 and PD-1. Analysis of differentially expressed genes
      in our canine populations revealed several genetic changes paralleling those
      known to occur in human disease. Naturally occurring canine glioma has many
      characteristics closely resembling human disease, particularly with respect to
      genetic dysregulation and host immune responses to tumors, supporting its use as
      a translational model in the preclinical testing of prospective anti-glioma
      therapies proven successful in murine studies.

PMID- 29330751
TI  - Prospective trial evaluating the sensitivity and specificity of 3,4-dihydroxy-6
      [18F]-fluoro-L-phenylalanine (18F-DOPA) PET and MRI in patients with recurrent
      gliomas.
AB  - Treatment-related changes can be difficult to differentiate from progressive
      glioma using MRI with contrast (CE). The purpose of this study is to compare the
      sensitivity and specificity of 18F-DOPA-PET and MRI in patients with recurrent
      glioma. Thirteen patients with MRI findings suspicious for recurrent glioma were
      prospectively enrolled and underwent 18F-DOPA-PET and MRI for neurosurgical
      planning. Stereotactic biopsies were obtained from regions of concordant and
      discordant PET and MRI CE, all within regions of T2/FLAIR signal hyperintensity.
      The sensitivity and specificity of 18F-DOPA-PET and CE were calculated based on
      histopathologic analysis. Receiver operating characteristic curve analysis
      revealed optimal tumor to normal (T/N) and SUVmax thresholds. In the 37 specimens
      obtained, 51% exhibited MRI contrast enhancement (M+) and 78% demonstrated 18F
      DOPA-PET avidity (P+). Imaging characteristics included M-P- in 16%, M-P+ in 32%,
      M+P+ in 46% and M+P- in 5%. Histopathologic review of biopsies revealed grade II
      components in 16%, grade III in 43%, grade IV in 30% and no tumor in 11%. MRI CE
      sensitivity for recurrent tumor was 52% and specificity was 50%. PET sensitivity
      for tumor was 82% and specificity was 50%. A T/N threshold > 2.0 altered
      sensitivity to 76% and specificity to 100% and SUVmax > 1.36 improved sensitivity
      and specificity to 94 and 75%, respectively. 18F-DOPA-PET can provide increased
      sensitivity and specificity compared with MRI CE for visualizing the spatial
      distribution of recurrent gliomas. Future studies will incorporate 18F-DOPA-PET
      into re-irradiation target volume delineation for RT planning.

PMID- 29330752
TI  - Evaluation of the iron regulatory protein-1 interactome.
AB  - The interactions of iron regulatory proteins (IRPs) with mRNAs containing an iron
      responsive element (IRE) is a major means through which intracellular iron
      homeostasis is maintained and integrated with cellular function. Although IRE-IRP
      interactions have been proposed to modulate the expression of a diverse number of
      mRNAs, a transcriptome analysis of the interactions that form within the native
      mRNA structure and cellular environment has not previously been described. An RNA
      CLIP study is described here that identified IRP-1 interactions occurring within
      a primary cell line expressing physiologically relevant amounts of mRNA and
      protein. The study suggests that only a small subset of the previously proposed
      IREs interact with IRP-1 in situ. Identifying authentic IRP interactions is not
      only important to a greater understanding of iron homeostasis and its integration
      with cell biology but also to the development of novel therapeutics that can
      compensate for iron imbalances.

PMID- 29330753
TI  - Transfer of critically ill adults-assessing the need for training.
AB  - BACKGROUND: Transfer of critically ill patients within the hospital is commonly
      associated with adverse incidents, but, despite this, no standardised training
      exists on how to carry out this task. Very little information is published in the
      literature on the learning needs of staff undertaking these transfers, and this
      limits our ability to provide a focused and appropriate educational intervention.
      AIMS: This study aimed to explore the organisational, environmental and
      individual issues that increase risk to patients during intrahospital transport
      (IHT) and to explore the potential educational solutions to these issues as
      articulated by these practitioners. METHODS: This qualitative descriptive study
      was conducted in an Irish tertiary hospital critical care unit. Semi-structured
      interviews were conducted on critical care practitioners until data saturation
      was achieved. After manual transcription of the data, they were then analysed to
      identify themes. RESULTS: Two themes emerged: challenges related to intrahospital
      transport and plans to improve intrahospital transport. CONCLUSIONS:
      Organisational, communication and individual issues need to be considered when
      addressing problems associated with IHT. A multifaceted approach is needed, with
      a focus on organisational solutions in the form of checklists as well as
      educational interventions such as interprofessional education initiatives.
      Further studies on implementation of educational initiatives will add to the
      findings we report here.

PMID- 29330754
TI  - Systematic Review of Mammography Screening Educational Interventions for Hispanic
      Women in the United States.
AB  - In the United States (U.S.), Hispanics experience breast cancer disparities.
      Breast cancer is the leading cause of cancer-related death among Hispanic women,
      and Hispanic women receive mammography screening at lower rates than some other
      ethnic groups. This low rate of screening mammography is associated with
      increased risk for possible late-stage diagnosis and lower survival rates.
      Educational interventions could play a role in increasing screening mammography
      rates among Hispanic women. This systematic review synthesized the current
      literature on educational interventions to increase mammography screening among
      Hispanic women. The review included studies published between May 2003 and
      September 2017 with experimental and quasi-experimental interventions to increase
      mammography screening among Hispanics in the U.S. Five studies out of an initial
      269 studies met inclusion criteria for the review. All studies employed an
      interpersonal intervention strategy with community health workers, or promotoras,
      to deliver the mammography screening intervention. For each study, odds ratios
      (OR) were calculated to estimate intervention effectiveness based on similar
      follow-up time periods. The study ORs resulted in a narrow range between 1.02 and
      2.18, indicating a low to moderate intervention effect for these types of
      interpersonal cancer education interventions. The summary OR for the random
      effects model was 1.67 (CI 1.24-2.26). Hispanics exhibit lower levels of
      adherence to screening mammography than non-Hispanic whites. Interpersonal cancer
      education interventions such as the use of promotoras may help to mediate the
      impact of barriers to receiving a mammogram such as low health literacy, deficits
      in knowledge about the benefits of screening, and low awareness of the
      availability of screening services.

PMID- 29330755
TI  - [Lymphoma in rheumatic diseases].
AB  - Various systemic inflammatory diseases, such as rheumatoid arthritis (RA),
      Sjogren's syndrome and systemic lupus erythematosus (SLE) are associated with an
      increased risk for the development of lymphomas. Studies on patients with RA and
      Sjogren's syndrome have shown that there is a clear association of the incidence
      of lymphoma with the severity and activity of the disease and lymphomas in
      particular are diseases which preferentially occur in immunosuppressed patients;
      therefore, knowledge of the different lymphoma subtypes, their prognosis and
      treatment options are important for rheumatologists. Currently, there is no
      evidence for an increased risk of lymphoma with the available conventional basis
      therapies or biologic disease-modifying antirheumatic drugs (DMARDs). The
      decision on how to treat a patient with previous lymphoma who requires
      antirheumatic treatment is more difficult as patients with previous malignancies
      are not included in clinical studies and in registries a bias with respect to
      patient selection must be taken into consideration. Decisions on the treatment
      approach, therefore need to be individualized and interdisciplinary management
      together with the treating hematologist is warranted.

PMID- 29330756
TI  - [Rheumatoid symptoms in patients with hematologic neoplasms].
AB  - Paraneoplastic syndromes in lymphatic or myeloid neoplasms can present with
      musculoskeletal symptoms, vasculitis-like or febrile symptoms. Hematologic
      diseases are also associated with rheumatic diseases whereas inflammatory
      rheumatic diseases are often associated with an increased risk for
      lymphoproliferative disease. Atypical disease characteristics, lack of disease
      specific antibodies or therapeutic response are red flags for diagnosing
      paraneoplastic or coexistent malignant diseases. New onset of systemic symptoms,
      worsening of general condition, night sweats or weight loss need to be considered
      during follow-up and differential diagnostics. This article focuses on
      musculoskeletal, vasculitis-like and systemic signs of lymphatic or myeloid
      neoplasms either because of coexistency, tumor association or paraneoplastic
      disease.

PMID- 29330757
TI  - [Myelodysplastic syndrome, acute leukemia and stem cell transplantation].
AB  - Myelodysplastic syndromes (MDS) represent a heterogeneous group of clonal
      hematopoietic stem cell disorders. They are characterized by inefficient
      hematopoiesis leading to peripheral cytopenia of one or more lineages and a
      variable risk of transformation into acute myeloid leukemia. They may either
      arise de novo as well as following exposition to environmental toxins, previous
      radiotherapy or chemotherapy or in the context of autoinflammatory diseases and
      related therapy. Characteristic cytogenetic abnormalities, along with the numbers
      of hematopoietic lineages affected and bone marrow blasts, enable an assessment
      of the risk of leukemic transformation. Acute leukemias are characterized by an
      accumulation of immature myeloid or lymphatic progenitor cells with limited
      differentiation capacity in the bone marrow. Proliferation of blast cells leads
      to suppression of normal hematopoiesis resulting in peripheral pancytopenia or
      leukocytosis associated with anemia and thrombocytopenia. Acute leukemias
      following MDS are defined as high-risk diseases. Intensive induction therapy
      followed by allogeneic stem cell transplantation is currently regarded as the
      only potentially curative treatment strategy. In this article the basic aspects
      of current diagnostics and treatment strategies for MDS and acute leukemia are
      outlined. Because of similarities with rheumatic inflammatory diseases,
      manifestations and treatment of graft versus host disease (GvHD) are also
      included.

PMID- 29330758
TI  - [Monoclonal gammopathy of undetermined significance and multiple myeloma].
AB  - In rheumatological practice monoclonal gammopathy of undetermined significance
      (MGUS) is a common incidental finding. Several rheumatic inflammatory diseases
      are known to have an elevated risk of MGUS, which can evolve into multiple
      myeloma or other lymphatic malignancies. The relevant definitions of disease
      entities are described, as well as algorithms for further diagnostic work-up and
      follow-up for monoclonal gammopathy, depending on the risk of progression.
      Therapeutic strategies against multiple myeloma are presented. Some of these
      therapeutic modalities could play a future role in treating plasma cell-dominated
      autoimmune diseases.

PMID- 29330759
TI  - [Autoimmune reactions to immune checkpoint inhibitors].
AB  - Immune checkpoint inhibitors (ICI) have dramatically changed the face of cancer
      treatment and are gaining in importance. The ICIs have now been approved for the
      treatment of advanced cancers, including melanoma, non-small-cell and small cell
      lung cancers, renal cell carcinoma, Hodgkin's lymphoma, head and neck cancers and
      urothelial carcinoma and further indications are to be expected. The organs most
      affected by an autoimmune reaction are the intestines, the musculoskeletal
      system, skin, endocrine organs, the liver and the lungs. As the indications for
      immune checkpoint blockade expand and ICIs are used in combination, it becomes
      increasingly more important for rheumatologists to recognize immune-related
      adverse events (irAEs), their connection to cancer immunotherapy and how to treat
      these events appropriately. The role of rheumatologists will take on growing
      importance as immunotherapies become more common as standard treatment of cancer
      and when used earlier in the course of the disease. Previously controlled
      autoimmune diseases can deteriorate when using ICIs, so this is a consideration
      when evaluating patients. Increased awareness of inflammatory arthritis, as well
      as other rheumatic manifestations as an adverse association with cancer
      immunotherapies, is imperative for making the diagnosis. Treatment algorithms are
      based on the severity of symptoms but in the case of rheumatic disease, treatment
      often needs to be tailored to the individual. The general strategy for evaluation
      and management of irAEs includes a thorough evaluation for infections. Mild irAE
      may be self-limiting, while more severe reactions are generally steroid
      responsive, albeit with potentially high dosage requirements.

PMID- 29330761
TI  - Correction to: Scientific white paper on concentration-QTc modeling.
AB  - The original version of this article unfortunately contained an error in Equation
      1 under the section "Pre-specified linear mixed effects model". The correct
      equation has given below.

PMID- 29330760
TI  - Oxidized phospholipids stimulate production of stem cell factor via NRF2
      dependent mechanisms.
AB  - Receptor tyrosine kinase c-Kit and its ligand stem cell factor (SCF) regulate
      resident vascular wall cells and recruit circulating progenitors. We tested
      whether SCF may be induced by oxidized palmitoyl-arachidonoyl-phosphatidylcholine
      (OxPAPC) known to accumulate in atherosclerotic vessels. Gene expression analysis
      demonstrated OxPAPC-induced upregulation of SCF mRNA and protein in different
      types of endothelial cells (ECs). Elevated levels of SCF mRNA were observed in
      aortas of ApoE-/- knockout mice. ECs produced biologically active SCF because
      conditioned medium from OxPAPC-treated cells stimulated activation
      (phosphorylation) of c-Kit in naive ECs. Induction of SCF by OxPAPC was inhibited
      by knocking down transcription factor NRF2. Inhibition or stimulation of NRF2 by
      pharmacological or molecular tools induced corresponding changes in SCF
      expression. Finally, we observed decreased levels of SCF mRNA in aortas of NRF2
      knockout mice. We characterize OxPLs as a novel pathology-associated stimulus
      inducing expression of SCF in endothelial cells. Furthermore, our data point to
      transcription factor NRF2 as a major mediator of OxPL-induced upregulation of
      SCF. This mechanism may represent one of the facets of pleiotropic action of NRF2
      in vascular wall.

PMID- 29330762
TI  - How honest are the signals? A protocol for validating wearable sensors.
AB  - There is growing interest among organizational researchers in tapping into
      alternative sources of data beyond self-reports to provide a new avenue for
      measuring behavioral constructs. Use of alternative data sources such as wearable
      sensors is necessary for developing theory and enhancing organizational practice.
      Although wearable sensors are now commercially available, the veracity of the
      data they capture is largely unknown and mostly based on manufacturers' claims.
      The goal of this research is to test the validity and reliability of data
      captured by one such wearable badge (by Humanyze) in the context of structured
      meetings where all individuals wear a badge for the duration of the encounter. We
      developed a series of studies, each targeting a specific sensor of this badge
      that is relevant for structured meetings, and we make specific recommendations
      for badge data usage based on our validation results. We have incorporated the
      insights from our studies on a website that researchers can use to conduct
      validation tests for their badges, upload their data, and assess the validity of
      the data. We discuss this website in the corresponding studies.

PMID- 29330764
TI  - The failing measurement of attitudes: How semantic determinants of individual
      survey responses come to replace measures of attitude strength.
AB  - The traditional understanding of data from Likert scales is that the
      quantifications involved result from measures of attitude strength. Applying a
      recently proposed semantic theory of survey response, we claim that survey
      responses tap two different sources: a mixture of attitudes plus the semantic
      structure of the survey. Exploring the degree to which individual responses are
      influenced by semantics, we hypothesized that in many cases, information about
      attitude strength is actually filtered out as noise in the commonly used
      correlation matrix. We developed a procedure to separate the semantic influence
      from attitude strength in individual response patterns, and compared these
      results to, respectively, the observed sample correlation matrices and the
      semantic similarity structures arising from text analysis algorithms. This was
      done with four datasets, comprising a total of 7,787 subjects and 27,461,502
      observed item pair responses. As we argued, attitude strength seemed to account
      for much information about the individual respondents. However, this information
      did not seem to carry over into the observed sample correlation matrices, which
      instead converged around the semantic structures offered by the survey items.
      This is potentially disturbing for the traditional understanding of what survey
      data represent. We argue that this approach contributes to a better understanding
      of the cognitive processes involved in survey responses. In turn, this could help
      us make better use of the data that such methods provide.

PMID- 29330763
TI  - Safe and sensible preprocessing and baseline correction of pupil-size data.
AB  - Measurement of pupil size (pupillometry) has recently gained renewed interest
      from psychologists, but there is little agreement on how pupil-size data is best
      analyzed. Here we focus on one aspect of pupillometric analyses: baseline
      correction, i.e., analyzing changes in pupil size relative to a baseline period.
      Baseline correction is useful in experiments that investigate the effect of some
      experimental manipulation on pupil size. In such experiments, baseline correction
      improves statistical power by taking into account random fluctuations in pupil
      size over time. However, we show that baseline correction can also distort data
      if unrealistically small pupil sizes are recorded during the baseline period,
      which can easily occur due to eye blinks, data loss, or other distortions.
      Divisive baseline correction (corrected pupil size = pupil size/baseline) is
      affected more strongly by such distortions than subtractive baseline correction
      (corrected pupil size = pupil size - baseline). We discuss the role of baseline
      correction as a part of preprocessing of pupillometric data, and make five
      recommendations: (1) before baseline correction, perform data preprocessing to
      mark missing and invalid data, but assume that some distortions will remain in
      the data; (2) use subtractive baseline correction; (3) visually compare your
      corrected and uncorrected data; (4) be wary of pupil-size effects that emerge
      faster than the latency of the pupillary response allows (within +/-220 ms after
      the manipulation that induces the effect); and (5) remove trials on which
      baseline pupil size is unrealistically small (indicative of blinks and other
      distortions).

PMID- 29330766
TI  - Simulaaneous ethanol and cellobiose inhibition of cellulose hydrolysis studied
      with integrated equations assuming constant or variable substrate concentration.
AB  - The integrated forms of the Michaelis-Menten equation assuming variable substrate
      (depletion) or constant substrate concentration were used to study the effect of
      the simultaneous presence of two exoglucanase Cel7A inhibitors (cellobiose and
      ethanol) on the kinetics of cellulose hydrolysis. The kinetic parameters
      obtained, assuming constant substrate (K m =21 mM, K ic =0.035 mM; K icl
      =1.5*1015mM; kcat=12 h-1) or assuming variable substrate (K m =16 mM, K ic =0.037
      mM; K icl =5.8*1014 mM; kcat=9 h-1), showed a good similarity between these two
      alternative methodologies and pointed out that bothethanol and cellobiose are
      competitive inhibitors. Nevertheless, ethanol is a very weak inhibitor, as shown
      by the large value estimated for the kinetic constant K icl . In addition,
      assuming different concentrations of initial accessible substrate present in the
      reaction, both inhibition and velocity constants are at the same order of
      magnitude, which is consistent with the obtained values. The possibility of using
      this kind of methodology to determine kinetic constants in general kinetic
      studies is discussed, and several integrated equations of different Michaelis
      Menten kinetic models are presented. Also examined is the possibility of
      determining inhibition constants without knowledge of the true accessible
      substrate concentration.

PMID- 29330765
TI  - Pudendal nerve terminal motor latency testing does not provide useful information
      in guiding therapy for fecal incontinence.
AB  - PURPOSE: Pudendal nerve terminal motor latency (PNTML) testing is a standard
      recommendation for the evaluation of fecal incontinence. Its role in guiding
      therapy for fecal incontinence has been previously questioned. The aim of this
      study was to evaluate the relationship between PNTML testing and anorectal
      dysfunction. METHODS: This was a retrospective analysis of data collected
      prospectively from patients who presented to a pelvic floor disorder center from
      2007 to 2015. The relationship between PNTML (normal versus delayed) and
      anorectal manometry, fecal incontinence severity, and fecal incontinence-related
      quality of life scores was assessed using the Wilcoxon-Mann-Whitney test.
      RESULTS: Two hundred sixty-nine patients underwent PNTML testing, and 91.1% were
      female (N = 245) (median age 62.2 years). Normal PNTML was seen in 234 (87.0%)
      patients. Among 268 patients who underwent anorectal manometry, delayed PNTML was
      only significantly associated with median maximum anal squeeze pressure (P =
      0.04). Delayed PNTML was not associated with a decrease in median fecal
      incontinence severity or fecal incontinence-related quality of life scores (N =
      99). CONCLUSIONS: PNTML was only associated with median maximum anal squeeze
      pressure, and it was not associated with patient-reported severity of symptoms of
      fecal incontinence, changes in quality of life attributable to fecal
      incontinence, median mean resting anal pressure, or median maximum resting anal
      pressure. PNTML testing may not be relevant to current therapeutic algorithms for
      fecal incontinence and its routine use should be questioned.

PMID- 29330767
TI  - Ivabradine for the Treatment of Postural Orthostatic Tachycardia Syndrome: A
      Systematic Review.
AB  - INTRODUCTION: Postural orthostatic tachycardia syndrome (POTS) impacts millions
      of patients, but there is currently no gold standard treatment for this
      condition. Ivabradine is a novel heart rate (HR) lowering agent that acts on the
      sinoatrial node cells by selectively inhibiting the If-current. OBJECTIVE: The
      objective of this systematic review is to evaluate the evidence for the efficacy
      and safety of ivabradine for the treatment of POTS. METHODS: MEDLINE (from 1956
      to August 2017) and EMBASE (from 1957 to August 2017) were queried with the
      following search term: "postural orthostatic tachycardia syndrome" OR "postural
      tachycardia syndrome" OR "chronic orthostatic intolerance" AND "ivabradine."
      Articles in English with clinical outcomes of human patient(s) treated with
      ivabradine for POTS were included. RESULTS: The initial search identified 73
      articles. After screening, 13 articles were included. Two prospective open-label
      trials, three retrospective cohort studies, and eight case reports evaluated the
      safety and efficacy of ivabradine in a total of 132 patients with postural
      tachycardia. Overall, ivabradine lowered HR and provided symptomatic relief of
      POTS without blood pressure lowering. Dizziness, nausea, headache, and fatigue
      were the most common side effects and often did not lead to discontinuation of
      treatment. CONCLUSION: Based on this small sample, ivabradine appears to be a
      reasonable option for patients with POTS who have failed or are unable to
      tolerate other treatment options, however, but a randomized controlled trial in
      this population is needed.

PMID- 29330768
TI  - Comorbid insomnia symptoms predict lower 6-month adherence to CPAP in US veterans
      with obstructive sleep apnea.
AB  - PURPOSE: There is limited information on the association between pre-treatment
      insomnia symptoms and dysfunctional sleep beliefs with continuous positive airway
      pressure (CPAP) adherence in veterans with obstructive sleep apnea (OSA). Our
      aims were to describe demographic and sleep characteristics of veterans with and
      without comorbid insomnia and determine whether pre-treatment insomnia symptoms
      and dysfunctional sleep beliefs predict CPAP use after 6 months of therapy.
      METHODS: Hispanic veterans attending the Miami VA sleep clinic were recruited and
      completed the insomnia severity index, the dysfunctional sleep belief and
      attitude scale (DBAS), and other questionnaires. Participants were asked to
      return after 7 days and 1 and 6 months to repeat questionnaires and for objective
      CPAP adherence download. Hierarchical regression models were performed to
      determine adjusted associations of pre-treatment insomnia symptoms and DBAS sub
      scores on 6-month mean daily CPAP use. RESULTS: Fifty-three participants
      completed the 6-month follow-up visit with a mean CPAP use of 3.4 +/- 1.9 h.
      Veterans with comorbid insomnia had lower mean daily CPAP use (168 +/- 125 vs 237
      +/- 108 min, p = 0.04) and lower percent daily CPAP use >= 4 h (32 +/- 32 vs 51
      +/- 32%, p = 0.05) compared to participants without insomnia. In adjusted
      analyses, pre-treatment insomnia symptoms (early, late, and aggregated nocturnal
      symptoms) and sleep dissatisfaction were predictive of lower CPAP use at 6
      months. Pre-treatment dysfunctional sleep beliefs were not associated with CPAP
      adherence. CONCLUSIONS: Pre-treatment nocturnal insomnia symptoms and sleep
      dissatisfaction predicted poorer 6- month CPAP use. Insomnia treatment preceding
      or concurrent with CPAP initiation may eliminate a barrier to regular use.

PMID- 29330769
TI  - Comorbid insomnia and sleep apnea in Veterans with post-traumatic stress
      disorder.
AB  - PURPOSE: The purpose of this study was to determine the impact of insomnia in
      Veterans with post-traumatic stress disorder (PTSD) and obstructive sleep apnea
      (OSA) on health-related outcomes before and after 12 weeks of continuous positive
      airway pressure (CPAP) treatment. METHODS: We conducted a prospective cohort
      study of Veterans with PTSD and documented apnea hypopnea index (AHI) >= 5 with
      and without clinically significant insomnia as determined by the Insomnia
      Severity Index (ISI). Health-related outcomes including PTSD checklist (PCL-M),
      SF-36, and Pittsburgh Sleep Quality Index (PSQI) were assessed at baseline and 12
      weeks after initiation of OSA treatment. CPAP adherence was retrieved at each
      visit. RESULTS: Seventy-two Veterans including 36 with comorbid insomnia and OSA
      (COMISA) and 36 OSA-only were enrolled. Veterans with COMISA were younger (p =
      0.03), had lower BMI (p < 0.001), and were more likely to report depression than
      those with OSA-only (p = 0.004). Although AHI was higher in the COMISA (p =
      0.01), both groups expressed comparable daytime sleepiness (p = 0.16). The COMISA
      group had no significant change in SF-36 and PSQI after 12 weeks of treatment and
      used CPAP much less frequently than OSA-only group (p = 0.001). CONCLUSIONS:
      COMISA in Veterans with PTSD is associated with worse quality of life than those
      with OSA-only. Insomnia should be assessed in Veterans with PTSD who are not
      adherent to CPAP treatment.

PMID- 29330770
TI  - Decoding Selection Bias Imparted by Unpaired Cysteines: a Tug of War Between
      Expression and Affinity.
AB  - In a recombinant antibody scFv format, the presence of an unpaired cysteine (Cys)
      is implicated in reduced soluble expression and inefficient presentation in phage
      display. Compared to other species, antibodies derived from rabbits are more
      likely to contain this unpaired Cys residue at position 80 (Cys80), when
      generated in a scFv format. In a screening campaign to isolate rabbit scFv
      against cardiac troponin I (cTnI), it was found that, a large proportion of
      isolated cTnI-specific clones contained unpaired Cys80. To analyze the factors
      that led to the selection of anti-cTnI Cys80 scFv, after five rounds of
      biopanning, the biopanning experiments were repeated with a Cys80 scFv (MG4Cys),
      its alanine variant (MG4Ala), and an irrelevant high expressing scFv control. It
      was found that the selection and subsequent enrichment of MG4Cys scFv was ousted
      by the superior expressing variant MG4Ala, indicating that the Cys80 scFv was
      selected primarily due to its affinity. It is evident that phage-based selection
      is influenced by specific sequence characteristics affecting the expression as
      well as the binding specificity and this needs to be taken into account for
      selection of optimal antibody derivatives.

PMID- 29330771
TI  - Inhibition of Human Immunodeficiency Type 1 Virus (HIV-1) Life Cycle by Different
      Egg White Lysozymes.
AB  - Lysozyme is a relatively small enzyme with different biological activities, which
      is found in tears, saliva, egg white, and human milk. In the study, the anti-HIV
      1 activity of lysozymes purified from quail, Meleagris, and hen egg white has
      been determined. For this end, a time-of-drug-addition assay was performed to
      identify the target of anti-HIV-1 agents and for determination of probable anti
      HIV-1 mechanism of the studied lysozyme, the binding affinity of the lysozymes to
      the human CD4 receptor was studied by molecular docking method. To define
      structural differences between studied lysozymes, structural motifs of them were
      predicted by MEME tool. Quail, hen, and Meleagris lysozymes showed potent anti
      HIV-1 activity with EC50 of 7.5, 10, and 55 nM, respectively. The time-of-drug
      addition study demonstrated that the inhibitory effect of all purified lysozymes
      is before HIV-1 infection. The frequency and intensity of CD4 expression in PBMCs
      decreased in the presence of all mentioned lysozymes. Also, the expression level
      of C-C chemokine receptor type 5 (CCR5) and chemokine receptor type 4 (CXCR4) on
      CD4+ T cells was not changed in cells treated with these lysozymes. The results
      of in silico study confirmed that the binding energy of quail lysozyme with CD4
      was more than that of other studied lysozymes. The results revealed that these
      lysozymes restrict HIV-1 attachment to host cell CD4.

PMID- 29330772
TI  - Rice WRKY11 Plays a Role in Pathogen Defense and Drought Tolerance.
AB  - BACKGROUND: Plants are frequently subjected to abiotic and biotic stresses, and
      WRKY proteins play a pivotal role in the response to such stress. OsWRKY11 is
      induced by pathogens, drought, and heat, suggesting a function in biotic and
      abiotic stress responses. RESULTS: This study identified OsWRKY11, a member of
      WRKY group IIc. It is a transcriptional activator that localized to the nucleus.
      Ectopic expression of OsWRKY11 resulted in enhanced resistance to a bacterial
      pathogen, Xanthomonas oryzae pv. oryzae; resistance was compromised in transgenic
      lines under-expressing OsWRKY11. Ectopic expression of OsWRKY11 resulted in
      constitutive expression of defense-associated genes, whereas knock-down (kd) of
      OsWRKY11 reduced expression of defense-associated genes during pathogen attack,
      suggesting that OsWRKY11 activates defense responses. OsWRKY11 bound directly to
      the promoter of CHITINASE 2, a gene associated with defense, and activated its
      transcription. In addition, ectopic expression of OsWRKY11 enhanced tolerance to
      drought stress and induced constitutive expression of drought-responsive genes.
      Induction of drought-responsive genes was compromised in OsWRKY11-kd plants.
      OsWRKY11 also bound directly to the promoter of a drought-responsive gene, RAB21,
      activating its transcription. In addition, OsWRKY11 protein levels were
      controlled by the ubiquitin-proteasome system. CONCLUSION: OsWRKY11 integrates
      plant responses to pathogens and abiotic stresses by positively modulating the
      expression of biotic and abiotic stress-related genes.

PMID- 29330774
TI  - A collection of XY female cell lines.
AB  - Discordance between sexual phenotype and the 46,XY sex chromosome complement may
      be found in certain disorders of sexual development (DSD). Many of these DSD
      patients with female external genitalia and secondary sex characteristics have
      undescended testes and male internal genitalia. Causative mutations involving
      genes of the sex determining pathway, including the androgen receptor, SRY and
      the 5-alpha-reductase genes, are well-known, but the origin of other cases remain
      unresolved. In this report, we introduce our collection of lymphoblastoid lines
      derived from female patients with a 46,XY karyotype. These cell lines have been
      deposited and registered with the JCRB Cell Bank. They are available for
      comparison with other DSD cases and for further characterization of genetic loci
      involved in the mammalian sex determining pathway.

PMID- 29330773
TI  - Mechanistic regulation of epithelial-to-mesenchymal transition through RAS
      signaling pathway and therapeutic implications in human cancer.
AB  - RAS effector signaling instead of being simple, unidirectional and linear
      cascade, is actually recognized as highly complex and dynamic signaling network.
      RAF-MEK-ERK cascade, being at the center of complex signaling network, links to
      multiple scaffold proteins through feed forward and feedback mechanisms and
      dynamically regulate tumor initiation and progression. Three isoforms of Ras
      harbor mutations in a cell and tissue specific manner. Besides mutations, their
      epigenetic silencing also attributes them to exhibit oncogenic activities. Recent
      evidences support the functions of RAS oncoproteins in the acquisition of tumor
      cells with Epithelial-to-mesenchymal transition (EMT) features/ epithelial
      plasticity, enhanced metastatic potential and poor patient survival. Google
      Scholar electronic databases and PubMed were searched for original papers and
      reviews available till date to collect information on stimulation of EMT core
      inducers in a Ras driven cancer and their regulation in metastatic spread.
      Improved understanding of the mechanistic basis of regulatory interactions of
      microRNAs (miRs) and EMT by reprogramming the expression of targets in Ras
      activated cancer, may help in designing effective anticancer therapies. Apparent
      lack of adverse events associated with the delivery of miRs and tissue response
      make 'drug target miRNA' an ideal therapeutic tool to achieve progression free
      clinical response.

PMID- 29330777
TI  - Focus on Novel Instrumentation in Mass Spectrometry and Ion Mobility
      Spectrometry.

PMID- 29330775
TI  - A PEG-based method for the isolation of urinary exosomes and its application in
      renal fibrosis diagnostics using cargo miR-29c and miR-21 analysis.
AB  - PURPOSE: To assess a new and highly specific, but low-cost, easily performed and
      suitable for large-scale applications method for renal fibrosis (RF) diagnostics.
      METHODS: Thirty-five RF and twenty non-RF patients were enrolled in the study. An
      appropriate polyethylene glycol (PEG) was used to isolate urinary exosomes. The
      efficiency of isolation process was evaluated by the morphology and size
      observation, as well as the detection of specific markers (CD63, CD9). The
      expression level of exosomal miR-29c, miR-21 and the endogenous control snRNA-U6
      were detected by qRT-PCR. The diagnostic potency of urinary exosomal miR-29c and
      miR-21 was estimated by the ROC method. Spearman's rank-order correlations
      analysis was used to assess the correlation between the miRNAs and clinical
      parameters, including pathological index. RESULTS: PEG-based method for isolation
      urinary exosome was effective and could be completed with a relatively low-speed
      centrifugal machine. Exosomal miR-29c and miR-21 were detected in all samples.
      The analysis of miRNAs in urinary exosomes revealed significant dys-regulation of
      miR-29c and miR-21 associated with RF. Exosomal miR-29c and miR-21 could predict
      degree of RF with AUC of 0.8333 and 0.7639 (P < 0.05). Correlation analysis
      showed that the level of miR-29c had a significant negative relationship with
      eGFR and the interstitial relative area. CONCLUSIONS: The PEG-based method for
      isolation urinary exosome is an inexpensive and easily performed approach. The
      application for cargo miRNA analysis is feasible. Urinary exosomal miR-29c may
      present a promising diagnostic approach.

PMID- 29330776
TI  - Second-Hand Exposure of Staff Administering Vaporised Cannabinoid Products to
      Patients in a Hospital Setting.
AB  - BACKGROUND: In many health settings, administration of medicinal cannabis poses
      significant implementation barriers including drug storage and safety for
      administering staff and surrounding patients. Different modes of administration
      also provide different yet potentially significant issues. One route that has
      become of clinical interest owing to the rapid onset of action and patient
      control of the inhaled amount (via breath timing and depth) is that of
      vaporisation of cannabinoid products. Although requiring a registered therapeutic
      device for administration, this is a relatively safe method of intrapulmonary
      administration that may be particularly useful for patients with difficulty
      swallowing, and for those in whom higher concentrations of cannabinoids are
      needed quickly. A particular concern expressed to researchers undertaking
      clinical trials in the hospital is that other patients, nurses, and clinical or
      research staff may be exposed to second-hand vapours in the course of
      administering vaporised products to patients. OBJECTIVE: The objective of this
      study was to take samples from two research staff involved in administering
      vaporised Delta9-tetrahydrocannabinol to participants in a clinical trial, to
      examine and quantitate cannabinoid presence. METHODS: Blood samples from two
      research staff were taken during the exposure period for three participants
      (cannabis users) over the course of approximately 2.5 h and analysed using tandem
      mass spectrometry. RESULTS: Blood samples taken over a vaporised period revealed
      exposure below the limit of detection for Delta9-tetrahydrocannabinol and two
      metabolites, using tandem mass spectrometry analytical methods. CONCLUSIONS:
      These results are reassuring for hospital and clinical trial practices with staff
      administering vaporised cannabinoid products, and helpful to ethics committees
      wishing to quantify risk.

PMID- 29330778
TI  - Isotopic Exchange HPLC-HRMS/MS Applied to Cyclic Proanthocyanidins in Wine and
      Cranberries.
AB  - Cyclic B-type proanthocyanidins in red wines and grapes have been discovered
      recently. However, proanthocyanidins of a different chemical structure (non
      cyclic A-type proanthocyanidins) already known to be present in cranberries and
      wine possess an identical theoretical mass. As a matter of fact, the retention
      times and the MS/MS fragmentations found for the proposed novel cyclic B-type
      tetrameric proanthocyanidin in red wine and the known tetrameric proanthocyanidin
      in a cranberry extract are herein shown to be identical. Thus, hydrogen/deuterium
      (H/D) exchange was applied to HPLC-HRMS/MS to confirm the actual chemical
      structure of the new oligomeric proanthocyanidins. The comparison of the results
      in water and deuterium oxide and between wine and cranberry extract indicates
      that the cyclic B-type tetrameric proanthocyanidin is the actual constituent of
      the recently proposed novel tetrameric species ([C60H49O24]+, m/z 1153.2608).
      Surprisingly, the same compound was also identified as the main tetrameric
      proanthocyanidin in cranberries. Finally, a totally new cyclic B-type hexameric
      proanthocyanidin ([C90H73O36]+, m/z 1729.3876) belonging to this novel class was
      identified for the first time in red wine. Graphical Abstract ?.

PMID- 29330779
TI  - Correction to: Age at disease onset and peak ammonium level rather than
      interventional variables predict the neurological outcome in urea cycle
      disorders.
AB  - Due to an unfortunate error during the typesetting process, the collaborators
      were presented incorrectly.

PMID- 29330780
TI  - Safety in Mixed Martial Arts: a 7-Year Review of Cancelled MMA Bouts in Calgary,
      Alberta, During the Pre-bout Medical Examination Period.
AB  - BACKGROUND: Presently, there is no literature that examines the reasons for the
      cancellation of amateur or professional mixed martial arts (MMA) bouts. The
      purpose of this study was to review the circumstances that lead to the
      cancellation of MMA bouts by Calgary ringside physicians during the pre-bout
      examination period and to identify any emerging patterns that may guide the
      regulatoin of this sport. METHODS: The case-series  was constructed from the
      Calgary Combative Sports Commission pre-bout examination records and the medical
      records submitted by each athlete from January 2010 to December 2016. RESULTS:
      Cancelled bouts in the pre-bout examination periods represented 5.4% of all MMA
      bouts in Calgary. A total of 25 reasons lead to bout cancellation and included
      the following: failure to obtain required neuroimaging (28.0%), neuroimaging
      abnormalities (24.0%), incomplete routine screening investigations (16.0%),
      exceeding maximum weight differential between the two athletes (16.0%), injury in
      the pre-competition period (8.0%), dehydration (4.0%), and ECG abnormalities
      (4.0%). The abnormalities on neuroimaging (n of 6) included the following: post
      traumatic gliosis on MRI (n = 1, 16.7%), flares diffusely and findings consistent
      with microhemorrhage on MRI (n = 1, 16.7%), chronic orbital fracture with fat pad
      extrusion on CT (n = 2, 33.3%), lacunar infarct on MRI (1), and unspecified MRI
      abnormality (n = 1, 16.7%). Twenty-two athletes had bouts cancelled and of these
      three athletes had their bouts stopped for two reasons. CONCLUSIONS: The
      following recommendations are presented and include: the creation of guidelines
      regarding pre- and post-bout neuroimaging, the implementation of industry-wide
      minimum medical screening standards, the adoption of a longitudinal approach to
      weight monitoring, the development of competent ringside physician groups, and
      active oversight by the Combative Sports Commission during the matchmaking
      process.

PMID- 29330781
TI  - A Review of the Methods and Associated Mathematical Models Used in the
      Measurement of Fat-Free Mass.
AB  - Fat-free mass (FFM) represents the lean component of the body devoid of fat. It
      has been shown to be a useful predictor of drug dose requirements, particularly
      in obesity where the excess fat mass does not contribute to drug clearance.
      However, measuring FFM involves complex and/or expensive experimental
      methodologies that preclude their use in routine clinical practice. Thus, models
      to predict FFM from readily measurable variables, such as body weight and height,
      have been developed and are used in both population pharmacokinetic modelling and
      clinical practice. In this review, methods used to measure FFM are explained and
      compared in terms of their assumptions, precision, and limitations. These methods
      are broadly classified into six different principles: densitometry, hydrometry,
      bioimpedance, whole-body counting, dual energy X-ray absorptiometry, and medical
      imaging. They vary in their processes and key biological assumptions that are
      often not applicable in certain populations (e.g. children, elderly, and certain
      disease states). This review provides a summary of the various methods of FFM
      measurement and estimation, and links these methods to a scientific framework to
      help clinicians and researchers understand the usefulness and potential
      limitations of these methods.

PMID- 29330782
TI  - Characterization of the Pharmacokinetics of Vilaprisan: Bioavailability,
      Excretion, Biotransformation, and Drug-Drug Interaction Potential.
AB  - BACKGROUND AND OBJECTIVES: In-vitro data suggest that clearance of vilaprisan is
      mediated by cytochrome P450 3A4 (oxidation) and aldoketoreductases (reduction).
      To fully understand the elimination and biotransformation pathways of vilaprisan,
      a selective progesterone receptor modulator, and to quantify the impact of
      cytochrome P450 3A4 inhibition on the pharmacokinetics of vilaprisan, two
      clinical studies in healthy postmenopausal women were conducted. METHODS: In
      study 1, pharmacokinetics, mass balance, and metabolite patterns were determined
      after single oral administration of 5 mg of [14C]-labeled vilaprisan in six
      subjects. In study 2, pharmacokinetics were determined after single oral
      administration of 4 mg of vilaprisan without and with concomitant administration
      of the strong cytochrome P450 3A4 inhibitor itraconazole (200 mg/day) in 14
      subjects. In addition, a microtracer dose of vilaprisan was given intravenously
      to determine absolute bioavailability, clearance, and volume of distribution.
      RESULTS: The dominant single compound in plasma was vilaprisan. No plasma
      metabolites exceeding 10% of total drug-related area under the concentration-time
      curve were detected. The absolute oral bioavailability of vilaprisan was ~ 60%.
      The mean clearance was ~ 7 L/h and the volume of distribution at steady state was
      ~ 360 L. Excretion occurred primarily via feces (73.5 +/- 3.70% of dose; urine:
      13.1 +/- 1.71%; total recovery: 86.6 +/- 2.81%), mostly in a metabolized form.
      Only small amounts of the parent drug were found in excreta. When vilaprisan was
      administered together with itraconazole, exposure to vilaprisan was increased 6.2
      fold (90% confidence interval 5.4-7.2). CONCLUSIONS: Vilaprisan is predominantly
      metabolized in the liver to a complex variety of metabolites, which are mainly
      excreted with feces. The pivotal role of cytochrome P450 3A4 in the metabolism of
      vilaprisan was confirmed. CLINICAL TRIAL REGISTRATION: EudraCT numbers 2013
      000707-16 (mass balance study) and 2014-004929-41 (drug-drug
      interaction/microtracer study); NCT02456129 (drug-drug interaction/microtracer
      study).

PMID- 29330783
TI  - Clinical Pharmacokinetics and Pharmacodynamics of Infliximab in the Treatment of
      Inflammatory Bowel Disease.
AB  - Infliximab was the first monoclonal antibody to be approved for the treatment of
      pediatric and adult patients with moderately to severely active Crohn's disease
      (CD) and ulcerative colitis (UC). It has been shown to induce and maintain both
      clinical remission and mucosal healing in pediatric and adult patients with
      inflammatory bowel disease (IBD) who are unresponsive or refractory to
      conventional therapies. The administration of infliximab is weight-based and the
      drug is administered intravenously. The volume of distribution of infliximab is
      low and at steady state ranges from 4.5 to 6 L. Therapeutic monoclonal
      antibodies, such as immunoglobulins, are cleared from the circulation primarily
      by catabolism. Median infliximab half-life is approximately 14 days. Infliximab
      concentration-time data in patients with CD and UC have been shown to be highly
      variable within an individual patient over time and between individuals by
      multiple population pharmacokinetic models. Covariates that have been identified
      to account for a part of the observed inter- and intra-individual variability in
      clearance are the presence of antidrug antibodies, use of concomitant
      immunomodulators, degree of systemic inflammation, serum albumin concentration,
      and body weight, which can affect the pharmacodynamic response. This article
      provides a comprehensive review of the clinical pharmacokinetics and
      pharmacodynamics of infliximab, as well as the role of therapeutic drug
      monitoring in the treatment of IBD.

PMID- 29330784
TI  - Tacrolimus Concentration in Saliva of Kidney Transplant Recipients: Factors
      Influencing the Relationship with Whole Blood Concentrations.
AB  - OBJECTIVE: The objective of this study was to examine the association between
      tacrolimus concentration in oral fluids and in whole blood and to investigate the
      various factors that influence this relationship. PATIENTS AND METHODS: Forty-six
      adult kidney transplant recipients were included in the study. Study A (ten
      patients) included the collection of several paired oral fluid samples by passive
      drool over a 12-h post-dose period. Study B (36 patients) included the collection
      of oral fluids pre-dose and at 2 h after the tacrolimus dose under three
      conditions: un-stimulated, after stimulation with a tart candy, and after mouth
      rinsing. The tacrolimus concentration in oral fluids was measured by a specially
      developed sensitive and specific liquid chromatography mass spectrometry method.
      A salivary transferrin concentration of >1 mg/dL was used as a cut-off value for
      oral fluid blood contamination. RESULTS: Rinsing the oral cavity before sampling
      proved to provide the most suitable sampling strategy giving a correlation
      coefficient value of 0.71 (p = 0.001) between the tacrolimus concentration in
      oral fluids and the tacrolimus concentration in whole blood at trough. Mean and
      95% confidence interval of tacrolimus concentration in oral fluids at the pre
      dose concentration for samples collected after mouth rinsing was 584 (436, 782)
      pg/mL. The ratio of the tacrolimus concentration in oral fluids to the tacrolimus
      concentration in whole blood (*100) was 11% (95% confidence interval 9-13) for
      all sampling times. Oral fluid pH or weight of a saliva sample did not influence
      the tacrolimus concentration in oral fluids. Tacrolimus distribution into oral
      fluids exhibited a delay with a pronounced counter-clockwise hysteresis with
      respect to the time after dose. A multivariate analysis of variance revealed that
      the tacrolimus concentration in oral fluids is related to the tacrolimus
      concentration in whole blood and tacrolimus plasma-binding proteins including
      albumin and cholesterol. CONCLUSION: An optimal sampling strategy for the
      determination of the tacrolimus concentration in oral fluids was established.
      Measuring the tacrolimus concentration in oral fluids appears to be a feasible
      and non-invasive method for predicting the concentration of tacrolimus in whole
      blood.

PMID- 29330785
TI  - Genetic Knockdown and Pharmacologic Inhibition of Hypoxia-Inducible Factor (HIF)
      Hydroxylases.
AB  - Reduced oxygen supply that does not satisfy tissue and cellular demand (hypoxia)
      regularly occurs both in health and disease. Hence, the capacity for cellular
      oxygen sensing is of vital importance for each cell to be able to alter its
      energy metabolism and promote adaptation to hypoxia. The hypoxia-inducible factor
      (HIF) prolyl hydroxylases 1-3 (PHD1-3) and the asparagine hydroxylase factor
      inhibiting HIF (FIH) are the primary cellular oxygen sensors, which confer
      cellular oxygen-dependent sensitivity upon HIF as well as other hypoxia-sensitive
      pathways, such as nuclear factor kappaB (NF-kappaB). Studying these enzymes
      allows us to understand the oxygen-dependent regulation of cellular processes and
      has led to the development of several putative novel therapeutics, which are
      currently in clinical trials for the treatment of anemia associated with kidney
      disease. Pharmacologic inhibition and genetic knockdown are commonly established
      techniques in protein biochemistry and are used to investigate the activity and
      function of proteins. Here, we describe specific protocols for the knockdown and
      inhibition of the HIF prolyl hydroxylases 1-3 (PHD1-3) and the asparagine
      hydroxylase factor-inhibiting HIF (FIH) using RNA interference (RNAi) and
      hydroxylase inhibitors, respectively. These techniques are essential tools for
      the analysis of the function of the HIF hydroxylases, allowing the investigation
      and discovery of novel functions and substrates of these enzymes.

PMID- 29330786
TI  - Kinetic Analysis of HIF Prolyl Hydroxylases.
AB  - Kinetic analyses of HIF prolyl 4-hydroxylases (HIF-P4Hs) allow determination of
      substrate, cosubstrate and cofactor requirements, analysis of the reaction rate,
      and inhibitory properties of the isoenzymes in vitro. Here we describe an assay
      measuring the substrate hydroxylation-coupled decarboxylation of radioactive 2
      oxoglutarate to radioactive carbon dioxide as a fast, efficient, and diverse
      method to analyze the enzyme kinetics of HIF-P4Hs.

PMID- 29330787
TI  - Mass Spectrometry and Bioinformatic Analysis of Hydroxylation-Dependent Protein
      Protein Interactions.
AB  - Characterization of how a stimulus regulates the dynamics of protein-protein
      interaction is critical for understanding how a particular protein is regulated
      in an intracellular signaling network. Protein hydroxylation, which is a
      posttranslational modification catalyzed by oxygen-dependent enzymes, is a
      crucial regulator of protein-protein interactions. Under low oxygen conditions,
      the activity of many hydroxylases is inhibited, which results in a reduction of
      substrate hydroxylation. These changes alter the interactome of the substrate,
      and this dynamic rewiring of signaling networks explains crucial aspects of the
      adaptive response to hypoxia. In order to fully understand the systemic role of
      hydroxylation, it is necessary to identify a comprehensive set of substrates, as
      well as to determine which residues are hydroxylated. In addition, hydroxylation
      dependent changes in the interactome of the substrates are indicative of the
      molecular function of the modification. To identify new substrates of
      hydroxylases, we have developed an approach involving the use of a
      pharmacological substrate-trap strategy followed by label-free quantitative mass
      spectrometry. An overview is provided for the sample preparation, mass
      spectrometry techniques, and statistical analysis used for detection of new
      substrates, hydroxylated residue, and hydroxylation-dependent protein-protein
      interaction changes.

PMID- 29330788
TI  - Acquisition of Temporal HIF Transcriptional Activity Using a Secreted Luciferase
      Assay.
AB  - Here we describe a simple method based on secreted luciferase driven by a hypoxia
      inducible factor (HIF) response element (HRE) that allows the acquisition of
      dynamic and high-throughput data on HIF transcriptional activity during hypoxia
      and pharmacological activation of HIF. The sensitivity of the assay allows for
      the secreted luciferase to be consecutively sampled (as little as 1% of the total
      supernatant) over an extended time period, thus allowing the acquisition of time
      resolved HIF transcriptional activity.

PMID- 29330790
TI  - Transcriptional Profiling Using RNA-Seq to Study Hypoxia-Mediated Gene
      Regulation.
AB  - Exposing cells to a hypoxic environment leads to significant physiological and
      molecular alterations. Most of the hypoxic responses are regulated by the
      transcription factors known as hypoxia-inducible factors (HIFs). HIF1, a
      heterodimer of hypoxia-stabilized subunit HIF-1alpha and a constitutively
      expressed subunit HIF-1beta, serves as a key transcription factor that regulates
      gene expressions which are involved in cell growth, metabolism, and
      proliferation. The global expression patterns can be analyzed by utilizing RNA
      Seq to understand the cellular alterations in hypoxia. This technique enables us
      to understand the comprehensive regulation of gene expression by specific factors
      or environmental stimuli. Here, we describe the complete process of studying
      hypoxia-mediated gene expression by using RNA-Seq, including the hypoxic
      treatment of cells, RNA isolation, RNA quality check, cDNA library preparation,
      and library quality check.

PMID- 29330789
TI  - Fluorescence Lifetime Imaging Microscopy (FLIM) as a Tool to Investigate Hypoxia
      Induced Protein-Protein Interaction in Living Cells.
AB  - Fluorescence resonance energy transfer (FRET) is widely used as a method to
      investigate protein-protein interactions in living cells. A FRET pair donor
      fluorophore in close proximity to an appropriate acceptor fluorophore transfers
      emission energy to the acceptor, resulting in a shorter lifetime of the donor
      fluorescence. When the respective FRET donor and acceptor are fused with two
      proteins of interest, a reduction in donor lifetime, as detected by fluorescence
      lifetime imaging microscopy (FLIM), can be taken as proof of close proximity
      between the fluorophores and therefore interaction between the proteins of
      interest. Here, we describe the usage of time-domain FLIM-FRET in hypoxia-related
      research when we record the interaction of the hypoxia-inducible factor-1 (HIF-1)
      subunits HIF-1alpha and HIF-1beta in living cells in a temperature- and CO2
      controlled environment under the microscope.

PMID- 29330791
TI  - Chromatin Immunoprecipitation of HIF-alpha in Breast Tumor Cells Using Wild Type
      and Loss of Function Models.
AB  - Chromatin immunoprecipitation (ChIP) is a powerful method to determine whether a
      protein of interest binds to specific regulatory elements of the genome. Herein,
      we outline protocols optimized to detect binding of Hypoxia-Inducible Factor
      (HIF)-1alpha or HIF-2alpha to putative hypoxia response elements (HREs) within
      HIF target genes expressed in breast tumor epithelial cells.

PMID- 29330792
TI  - Evaluating the Metabolic Impact of Hypoxia on Pancreatic Cancer Cells.
AB  - Hypoxia is frequently observed in human cancers and induces global metabolic
      reprogramming that includes an increase in glucose uptake and glycolysis,
      alterations in NAD(P)H/NAD(P)+ and intracellular ATP levels, and increased
      utilization of glutamine as the major precursor for fatty acid synthesis. In this
      chapter, we describe in detail various physiological assays that have been
      adopted to study the metabolic shift propagated by exposure to hypoxic conditions
      in pancreatic cell culture model that includes glucose uptake, glutamine uptake,
      and lactate release by pancreatic cancer cell lines. We have also elaborated the
      assays to evaluate the ratio of NAD(P)H/NAD(P)+ and intracellular ATP estimation
      using the commercially available kit to assess the metabolic state of cancer
      cells.

PMID- 29330793
TI  - Hypoxia-Induced Metabolomic Alterations in Pancreatic Cancer Cells.
AB  - Hypoxic conditions in the pancreatic tumor microenvironment lead to the
      stabilization of hypoxia-inducible factor-1 alpha (HIF-1alpha), which acts as the
      master regulator of cancer cell metabolism. HIF-1alpha-mediated metabolic
      reprogramming results in large-scale metabolite perturbations. Characterization
      of the metabolic intermediates and the corresponding metabolic pathways altered
      by HIF-1alpha would facilitate the identification of therapeutic targets for
      hypoxic microenvironments prevalent in pancreatic ductal adenocarcinoma and other
      solid tumors. Targeted metabolomic approaches are versatile in quantifying
      multiple metabolite levels in a single platform and, thus, enable the
      characterization of multiple metabolite alterations regulated by HIF-1alpha. In
      this chapter, we describe a detailed metabolomic approach for characterizing the
      hypoxia-induced metabolomic alterations using pancreatic cancer cell lines
      cultured in normoxic and hypoxic conditions. We elaborate the methodology of cell
      culture, hypoxic exposure, metabolite extraction, and relative quantification of
      polar metabolites from normoxia- and hypoxia-exposed cell extracts, using a
      liquid chromatography-coupled tandem mass spectrometry approach. Herein, using
      our metabolomic data, we also present the methods for metabolomic data
      representation.

PMID- 29330794
TI  - Hypoxia-Mediated In Vivo Tumor Glucose Uptake Measurement and Analysis.
AB  - Most solid tumors are hypoxic in nature due to the limited supply of oxygen to
      internal tissues. Hypoxia plays an important role in metabolic adaptations of
      tumors that contribute significantly to cancer pathogenesis. Among the several
      metabolic alterations induced by hypoxia, hypoxia-mediated increased glucose
      uptake serves as the hallmark of metabolic reprogramming. Hypoxia-mediated
      stabilization of hypoxia-inducible factor-1 alpha (HIF-1alpha) transcription
      factor leads to altered expression of several glycolytic genes and glucose
      transporters, which results in increased glucose uptake by tumor cells. Here we
      describe an easy and simple way of measuring the hypoxia-mediated tumor glucose
      uptake in vivo. The method is based on fluorescent imaging probe, RediJect 2-DG,
      which is a nonradioactive fluorescent-tagged glucose molecule. We have discussed
      orthotopic tumor implantation of HIF-1alpha knockdown and control pancreatic
      cancer cells and glucose uptake measurement in vivo by using IVIS imaging system
      along with reagent preparations.

PMID- 29330795
TI  - Measurement of Sensory Nerve Activity from the Carotid Body.
AB  - Carotid bodies are sensory organs for monitoring chemical composition of the
      arterial blood, especially the O2 levels. Carotid bodies are located bilaterally
      at the bifurcation of the common carotid artery. Hypoxia increases sensory nerve
      activity of the carotid body, which is transmitted to the brainstem neurons
      triggering reflex stimulation of breathing and blood pressure. Measurement of
      action potentials from the carotid sinus nerve is a widely used approach for
      understanding the mechanisms of hypoxic sensing by the carotid body. Here, we
      describe the detailed methodology for recording action potential signals from the
      carotid sinus nerve from in vivo and ex vivo carotid bodies from rats.

PMID- 29330796
TI  - Monitoring Functional Responses to Hypoxia in Single Carotid Body Cells.
AB  - The carotid body is the main arterial chemoreceptor in mammals that mediates the
      cardiorespiratory reflexes activated by acute hypoxia. Here we describe the
      protocols followed in our laboratory to study responsiveness to hypoxia of
      single, enzymatically dispersed, glomus cells monitored by microfluorimetry and
      the patch-clamp technique.

PMID- 29330797
TI  - Testing Acute Oxygen Sensing in Genetically Modified Mice: Plethysmography and
      Amperometry.
AB  - Monitoring responsiveness to acute hypoxia of whole animals and single cells is
      essential to investigate the nature of the mechanisms underlying oxygen (O2)
      sensing. Here we describe the protocols followed in our laboratory to evaluate
      the ventilatory response to hypoxia in normal and genetically modified animals.
      We also describe the amperometric technique used to monitor single-cell
      catecholamine release from chemoreceptor cells in carotid body and adrenal
      medulla slices.

PMID- 29330798
TI  - Immunohistochemistry of the Carotid Body.
AB  - Immunohistochemistry (IHC) enables the detection and distribution of proteins in
      cells of tissues. IHC has become an indispensable approach for studying oxygen
      sensing by the carotid body (CB). This chapter provides a detailed description of
      IHC of CB tissue and isolated CB cells.

PMID- 29330799
TI  - Hypoxia Signaling and Placental Adaptations.
AB  - Oxygen is an essential nutrient for cells. Oxygen is delivered to tissues via red
      blood cells through the vasculature. Molecular mechanisms mediating cellular
      responses to low oxygen tension have been identified. Hypoxia-inducible factors
      (HIFs) are activated by low oxygen and promote transcriptional regulation of
      downstream effector genes, which lead to cellular adaptations. Controlled hypoxia
      exposure is utilized as an experimental tool to investigate biological processes,
      regulating cellular adaptations. Here we describe detailed protocols for hypoxia
      exposure of pregnant rodent models and low oxygen exposure of trophoblast stem
      cells, utilizing gas-regulated chamber systems. The presentation also includes
      phenotypic analyses of the manipulated animal models and cells.

PMID- 29330800
TI  - Evaluation of Erythrocyte Changes After Normoxic Return from Hypoxia.
AB  - Hypoxia increases erythropoiesis by hypoxia-inducible factors (HIF), principally
      by HIF-2, which upregulates erythropoietin transcription. This results in an
      increase of red blood cell (RBC) production and delivery of more oxygen to
      tissues. Upon rapid return to normoxia, hypoxia-induced polycythemia is
      overcorrected by neocytolysis, a transient destruction of preferentially young
      RBCs bearing low catalase (downregulated by hypoxia-stimulated microRNA(miR)-21)
      caused by reactive oxygen species (ROS) from expanded mitochondria. In order to
      study molecular mechanism of neocytolysis, it is critical to differentiate life
      span of young and old RBCs and to measure the hematological changes before and
      after hypoxia treatment. Here we describe the methodological aspects of these
      measurements.

PMID- 29330801
TI  - Hypoxic Treatment of Zebrafish Embryos and Larvae.
AB  - Zebrafish has emerged as an informative animal model to study the biological
      impact and molecular mechanisms of hypoxia. Here we describe a simple method to
      induce hypoxia in zebrafish embryos and larvae. This protocol is easy and
      reproducible and does not require expensive equipment or specialized devices. It
      can be adapted in large, medium, and small scales. This protocol is also well
      suited for experiments requiring chemical drug treatment and can be applied to
      other fish and amphibian species.

PMID- 29330802
TI  - Microinjection of Antisense Morpholinos, CRISPR/Cas9 RNP, and RNA/DNA into
      Zebrafish Embryos.
AB  - In this chapter, we describe a stepwise protocol of microinjection. Using this
      method, antisense morpholinos, CRISPR-Cas9 ribonucleoprotein complexes, capped
      mRNA, and DNA can be delivered into fertilized zebrafish eggs to manipulate gene
      expression during development. This protocol can also be adapted for
      microinjection in other fish and amphibian species.

PMID- 29330803
TI  - Western Blot Analysis of C. elegans Proteins.
AB  - C. elegans has been widely used as a model organism for basic biological research
      and is particularly amenable for molecular genetic studies using a broad
      repertoire of techniques. Biochemical approaches, including Western blot
      analysis, have emerged as a powerful tool in C. elegans biology for understanding
      molecular mechanisms that link genotypes to phenotypes. Here, we provide a
      protocol for Western blot analysis using protein extracts obtained from C.
      elegans samples.

PMID- 29330804
TI  - In Vivo Manipulation of HIF-1alpha Expression During Glioma Genesis.
AB  - Hypoxia has long been recognized as a driving force of tumor progression and
      therapeutic resistance, and the transcription factor HIF-1alpha is believed to
      play a crucial role in these processes. Here we describe an efficient RCAS/Nes
      TVA system that allows for in vivo manipulation of HIF-1alpha expression in the
      mouse neural progenitor cells. Simple production of the recombinant avian virus
      RCAS enables quick delivery of gene of interest through injection into the neural
      progenitors of transgenic mice expressing the viral cognate receptor TVA under
      the nestin promoter. By crossing with various commercially available genetically
      engineered mouse strains, a repertoire of mouse models can be created to study
      gene-specific effects on glioma genesis. This chapter provides details of plasmid
      construction, viral production, and intracranial delivery of transgenes, a
      methodology that can be easily adapted to a specific purpose.

PMID- 29330805
TI  - In Vitro Assays of Breast Cancer Stem Cells.
AB  - Aldehyde dehydrogenase and mammosphere assays enable the cost-effective
      quantification and characterization of cancer stem cells (CSCs) from cancer cell
      lines as well as cancer tissue. Here we describe the quantification of CSCs in
      breast cancer cell lines using aldehyde dehydrogenase and mammosphere assays
      under hypoxic (1% O2) and non-hypoxic (20% O2) culture conditions. Using this
      method, a significant enrichment of CSCs compared to bulk populations is observed
      when breast cancer cells are exposed to 1% O2 for 72 h.

PMID- 29330806
TI  - Fluorescence-Activated Cell Sorting of Murine Mammary Cancer Stem-Like Cell
      Subpopulations with HIF Activity.
AB  - Fluorescence-activated cell sorting (FACS) is a common method to identify and to
      isolate subpopulations within a complex mixture of cells based on their light
      scatter and fluorescent staining profiles. FACS is widely used to enrich for
      normal tissue and tumor cells that have stem cell potential. Whereas FACS
      protocols using conventional breast cancer cell lines are relatively routine,
      additional technical challenges are encountered when sorting for cell populations
      from freshly digested solid tumors, particularly for use in downstream cancer
      stem cell (CSC) assays. First, it is more difficult to isolate live, single cells
      from whole tumors, and second, single tumor cells prepared from enzymatically
      digested tumors are typically more sensitive to cell death following the physical
      stresses of digestion, pipetting, and sorting. Herein methods are described that
      have been optimized to harvest and to FACS profile viable tumor epithelial cells
      digested from late-stage mammary tumors originating in the mouse mammary tumor
      virus (MMTV)-polyomavirus middle T antigen (PyMT) transgenic mouse. Protocols
      were designed to enrich for single, viable, MMTV-PyMT tumor cell populations
      sorted by FACS and to facilitate the collection of sorted cell subpopulations
      suitable for head-to-head comparison of CSC activity by tumorsphere assays in
      vitro or limiting dilution transplantation in vivo.

PMID- 29330807
TI  - Evaluation of Macrophage Polarization in Pancreatic Cancer Microenvironment Under
      Hypoxia.
AB  - Hypoxic microenvironment found in pancreatic ductal adenocarcinoma and other
      solid tumors is central to physiological and metabolic alterations of immune
      cells that significantly impact tumor growth dynamics. Hypoxic adaptations in the
      immune cells are primarily mediated by the stabilization of hypoxia-inducible
      factor-1 alpha (HIF-1alpha), which regulates cellular metabolism by modulating
      glycolysis and other interconnected metabolic pathways. HIF-1alpha plays distinct
      roles in M1 and M2 macrophage polarization, which, in turn, regulates tumor cell
      immune escape and growth. In this chapter, we describe a real-time PCR-based
      assay to monitor the transcript levels of Arg1 and Nos2 to assess the status of
      tumor-induced macrophage polarization under hypoxic conditions. This method can
      be effectively utilized to delineate the genes critical for M1/M2 polarization in
      the hypoxic tumor microenvironment and would provide opportunities to develop
      immunomodulating therapies to regulate the tumor growth, progression, and
      metastatic dissemination.

PMID- 29330808
TI  - Detection of Hypoxia and HIF in Paraffin-Embedded Tumor Tissues.
AB  - Hypoxia (insufficient O2 availability) is involved in various biological
      processes, such as tumorigenesis and inflammation. Hypoxia results in
      stabilization of hypoxia-inducible factors (HIFs) including HIF1alpha and
      HIF2alpha. Here we describe a protocol to detect mouse and human tissue hypoxia
      by using Hypoxyprobe and immunohistochemical staining for HIF1alpha and
      HIF2alpha.

PMID- 29330809
TI  - Analysis of Hypoxia and the Hypoxic Response in Tumor Xenografts.
AB  - Solid tumors are often characterized by insufficient oxygen supply (hypoxia), as
      a result of inadequate vascularization, which cannot keep up with the rapid
      growth rate of the tumor. Tumor hypoxia is a negative prognostic and predictive
      factor and is associated with a more aggressive phenotype in various tumor
      entities. Activation of the hypoxic response in tumors, which is centered around
      the hypoxia-inducible transcription factors (HIFs), has been causally linked to
      neovascularization, increased radio- and chemoresistance, altered cell
      metabolism, genomic instability, increased metastatic potential, and tumor stem
      cell characteristics. Thus, the hypoxic tumor microenvironment represents a main
      driving force for tumor progression and a potential target for therapeutic
      interventions. Here, we describe several methods for the analysis of tumor
      hypoxia and the hypoxic response in vivo in tumor xenograft models. These methods
      can be applied to various tumor models, including brain tumor xenotransplants,
      and allow simultaneously determining the extent and distribution of hypoxia
      within the tumor, analyzing HIF levels by immunohistochemistry and immunoblot,
      and quantifying the expression of HIF target genes in tumor tissue. The
      combination of these approaches provides an important tool to assess the role of
      the hypoxic tumor microenvironment in vivo.

PMID- 29330810
TI  - Correlation of Glioma Proliferation and Hypoxia by Luciferase, Magnetic
      Resonance, and Positron Emission Tomography Imaging.
AB  - Gliomas are the most common type of primary, malignant brain tumor and
      significantly impact patients, who have a median survival of ~1 year depending on
      mutational background. Novel imaging modalities such as luciferase
      bioluminescence, micro-magnetic resonance imaging (micro-MRI), micro-computerized
      tomography (micro-CT), and micro-positron emission tomography (micro-PET) have
      expanded the portfolio of tools available to study this disease. Hypoxia, a key
      oncogenic driver of glioma and mechanism of resistance, can be studied in vivo by
      the concomitant use of noninvasive MRI and PET imaging. We present a protocol
      involving stereotactic injection of syngenic F98 luciferase-expressing glioma
      cells generated by our laboratory into Fischer 344 rat brains and imaging using
      luciferase. In addition, 18-F-fludeoxyglucose, 18F-fluoromisonidazole, and 18F
      fluorothymidine PET imaging are compared with quantified luciferase flux. These
      tools can potentially be used for assessing tumor growth characteristics,
      hypoxia, mutational effects, and treatment effects.

PMID- 29330811
TI  - A nationwide survey of factors influencing adherence to ocular hypotensive
      eyedrops in Japan.
AB  - INTRODUCTION: Few reports have investigated the status of adherence in Japan on a
      large scale. We aimed to investigate the status of adherence to topical glaucoma
      treatment and its associated factors. METHODS: A nationwide survey was conducted
      as a prospective fashion. Participants in this survey were subjects with primary
      open-angle glaucoma, normal-tension glaucoma, or ocular hypertension or
      pseudoexfoliation glaucoma who had been prescribed anti-glaucoma ophthalmic
      eyedrops and whose ophthalmologist considered prescribing any fixed combination
      of ocular hypotensive eyedrops for the first time between 2011 and 2012. Subjects
      and their attending ophthalmologists independently completed a questionnaire by
      utilizing a fixed combination of ocular hypotensive eyedrops. RESULTS: A total of
      1358 ophthalmologists from 1071 medical institutions participated in this survey.
      We registered 4430 subjects (2049 males and 2381 females). In total, data from
      3853 subjects (87.6%) were analyzed after inclusion of subjects based on
      inclusion and exclusion criteria. Good adherence was defined as not forgetting
      instillation during the past week. Rates of good adherence reported by subjects
      and ophthalmologists were 72.4 and 78.5%, respectively (P < 0.0001). The
      consistency of adherence evaluation between subjects and ophthalmologists was
      moderate [kappa score 0.5025 (95% confidence interval 0.4740-0.5309)].
      Significant factors associated with adherence were size of clinic, age, gender,
      number of types of ocular hypotensive eyedrops, ease of instillation, preferred
      number of eyedrops, preferred frequency of instillation of eyedrops, and
      knowledge of glaucoma. CONCLUSION: Adherence to ocular hypotensive eyedrops among
      Japanese subjects was relatively good. Concordance of adherence between subjects'
      reports and ophthalmologists' responses was moderate. Size of clinic, number of
      types of ocular hypotensive eyedrops, ease of instillation, preferred number of
      eyedrops, preferred frequency of instillation of eyedrops, and knowledge of
      glaucoma were associated with adherence among Japanese glaucoma subjects.

PMID- 29330813
TI  - Characteristics of Elderly Patients Initiating Sitagliptin or Non-DPP-4-Inhibitor
      Oral Antihyperglycemic Agents: Analysis of a Cross-Sectional US Claims Database.
AB  - INTRODUCTION: Previous analyses concluded that patients initiating treatment with
      sitagliptin are older and have more comorbidities than patients initiating
      treatment with other oral antihyperglycemic agents (OAHAs). However, these
      studies focused on the general population or subjects <= 65 years of age. We
      sought to compare differences in baseline characteristics of elderly patients (>=
      65 years of age) with T2DM initiating sitagliptin vs. non-DPP-4 inhibitor (non
      DPP-4i) OAHA in the MarketScan(r) Medicare Supplemental Database. METHODS:
      Relevant patients were identified in the MarketScan(r) Medicare Supplemental
      Database and categorized according to the complexity of their antihyperglycemic
      treatment: initiating monotherapy, escalating to dual combination therapy, or
      escalating to triple combination therapy. Within each category, the comparison
      between patients initiating use of sitagliptin or non-DPP-4i OAHA was made within
      three age groups: 65-74, 75-84, and >= 85 years. Gender and comorbidity recorded
      within the 12 months prior to the index date (date of initiation/escalation of
      treatment) were assessed as baseline characteristics in each group. Between
      treatment group differences in each covariate were compared using standardized
      differences. RESULTS: Patients with T2DM who initiated treatment with sitagliptin
      tended to be older and were more likely to have a pre-treatment history of
      arrhythmia, congestive heart failure, peripheral vascular disease, renal failure,
      and stroke than those initiating non-DPP-4i OAHAs, with the most pronounced
      differences observed between patients initiating monotherapy in all three age
      groups. As treatment complexity advanced to dual combination therapy, the
      differences were attenuated and mostly observed in the 75-84 and >= 85 age
      groups. In patients aged 65-74 years initiating triple therapy, no differences
      were observed between groups. CONCLUSION: Patients >= 65 years with T2DM
      initiating sitagliptin tend to be older and have more comorbidities than those
      prescribed other classes of OAHA. Appropriate adjustment is required to minimize
      the impact of potential confounding and channeling bias in any comparative
      analyses including users of sitagliptin. FUNDING: Merck & Co., Inc., Kenilworth,
      NJ, USA.

PMID- 29330812
TI  - Evaluation of the Effect of Alogliptin on Tissue Characteristics of the Carotid
      Wall: Subanalysis of the SPEAD-A Trial.
AB  - INTRODUCTION: Ultrasonic tissue characterization of the carotid wall using gray
      scale median (GSM) reflects its composition and low-GSM plaque is considered to
      be unstable. The present study evaluated the effect of alogliptin, a dipeptidyl
      peptidase-4 inhibitor, on the longitudinal change in GSM, an index of the tissue
      characteristics of the carotid wall, in patients with type 2 diabetes (T2DM).
      METHODS: This is a post hoc subanalysis using data obtained from the SPEAD-A
      trial, a randomized controlled trial that demonstrated the beneficial effect of
      alogliptin treatment on the progression of carotid intima-media thickness in
      patients with T2DM with no past history of apparent cardiovascular disease. A
      total of 322 subjects (161 in the alogliptin treatment group and 161 in the
      conventional treatment group) were enrolled. The primary outcome was the change
      from baseline in mean GSM-CCA (common carotid artery) during the 104-week
      observation period. RESULTS: Both alogliptin treatment and conventional treatment
      significantly increased the mean GSM-CCA (from 60.7 +/- 12.3 to 65.9 +/- 10.1, p
      < 0.001 and 58.8 +/- 14.4-65.2 +/- 12.2, p < 0.001, respectively) and there was
      no significant difference in changes in mean GSM-CCA between the treatment groups
      (p = 0.95). Additionally, there were no differences in the changes in the left
      and right GSM-CCA between the groups. CONCLUSIONS: A post hoc subanalysis
      revealed an improvement of tissue characteristics in the carotid arterial wall in
      both the alogliptin treatment group and the conventional treatment group during
      the 104-week treatment period and that there was no significant difference
      between the treatment groups. CLINICAL TRIAL REGISTRATION: UMIN000019951.

PMID- 29330814
TI  - Contrasting effects of alkaline amendments on the bioavailability and uptake of
      Cd in rice plants in a Cd-contaminated acid paddy soil.
AB  - Reducing cadmium (Cd) concentrations in rice grains is important for food safety,
      particularly in acid paddy fields in South China where the soils have been
      previously contaminated with Cd. A field experiment was conducted to evaluate the
      effects of four alkaline amendments, i.e., lime, compost, biochar, and carbide
      slag on soil bioavailability and uptake of Cd in plants of two rice cultivars
      (Oryza sativa L.) in a Cd-contaminated acid paddy soil. The addition of these
      amendments significantly decreased the concentrations of CaCl2-extractable Cd by
      13-41%. Cd in the acid-soluble fraction was decreased in these amended soils
      while it increased in the residual fraction. The amendments also decreased the
      uptake of Cd in the plants at the tillering and mature growth stages. The
      concentrations of Cd in plant tissues at maturity were in the order: root > shoot
      > bran > polished rice > husk. The amendment of carbide slag decreased Cd
      concentration in rice grains the most, followed by lime, biochar, and compost.
      The increases in soil pH and the decreases in the acid-soluble fraction of Cd (F1
      Cd) indicated that these amendments can directly transform the highly
      availability fraction of Cd to a more stable fraction (residual Cd fraction) in
      soils. Furthermore, the Cd concentrations in polished rice grains of the two rice
      cultivars used were reduced by 66-67% by treatment with carbide slag. Our study
      suggests that carbide slag has a great potential to reduce the bioavailability
      and uptake of Cd in rice plants in Cd-contaminated acid paddy field soils.

PMID- 29330815
TI  - Supplementing dietary rosemary (Rosmarinus officinalis L.) powder and vitamin E
      in broiler chickens: evaluation of humoral immune response, lymphoid organs, and
      blood proteins.
AB  - The aim of the present study was to evaluate the effect rosemary (Rosmarinus
      officinalis L.) powder (RP) and vitamin E (VE) at different levels on humoral
      immunity of broilers during a 42-day production cycle. A total of 270 1-day-old
      male chicks were assigned to nine groups with three replicates of ten birds each,
      and diets were supplemented with 0, 0.5, or 1.0% RP and 0, 100, or 200 mg/kg VE,
      respectively. Commercial-inactivated vaccines against avian influenza (AI) and
      Newcastle disease (ND) viruses, and living infectious bronchitis virus (IBV)
      vaccine were administered by spray method. Sheep red blood cells (SRBC) were
      administered subcutaneously. Blood samples were collected from birds 1 week after
      each vaccination to determine antibody titers. At the 42nd day, blood samples
      were also assessed for globulin level, and lymphoid tissues (thymus, spleen, and
      bursa) were weighed. Neither antibody titers against viruses nor lymphoid tissues
      weight were affected by RP and/or VE (P > 0.05) treatments. However, broilers
      supplemented with 0 mg/kg of VE had lower antibody titers against SRBC than those
      fed 100 mg/kg of VE (P < 0.05) at the 24th day. A significant RP * VE interaction
      effect (P < 0.05) on plasma globulin level was observed. The findings of our
      study suggest that dietary RP and VE additives can interact and modulate the
      humoral immunity of broilers, but not sufficiently to improve antibody titers
      against specific virus during a 42-day production cycle.

PMID- 29330816
TI  - Testing the role of external debt in environmental degradation: empirical
      evidence from Turkey.
AB  - This study investigates the role of external debt stock in Turkey, which has
      suffered from heavy (external and domestic) debt stock for many years. Annual
      data from 1960 to 2013 was analyzed using time series analysis in order to study
      this. The results confirm the validity of the conventional environmental Kuznets
      curve (EKC) in the case of Turkey. However, this study also found that Turkey's
      external debt stock did not influence the Turkish economy's long-term EKC
      behavior. Fortunately, the results suggest that there are important interactions
      among external debt stock, CO2 emissions, energy consumption, and real income;
      that is, changes in external debt volume precede changes in these aggregates'
      volumes.

PMID- 29330817
TI  - Effect of levofloxacin, pazufloxacin, enrofloxacin, and meloxicam on the
      immunolocalization of ABCG-2 transporter protein in rabbit retina.
AB  - Adenosine triphosphate-binding cassette (ABC) sub-family G member-2 (ABCG-2) is a
      transporter protein, implicated for multi-drug efflux from tissues. This study
      evaluated the effect of fluoroquinolones; levofloxacin, pazufloxacin and
      enrofloxacin, and non-steroidal anti-inflammatory drug, meloxicam; on the
      immunolocalization of ABCG-2 transporter protein of rabbit retinas. Thirty-two
      male rabbits were randomly divided in to eight groups. Control group was gavaged,
      2% benzyl alcohol in 5% dextrose since these chemicals are excipients of the drug
      preparations used in the treatment groups of this study. Four groups were
      exclusively gavaged, levofloxacin hemihydrate (10 mg/kg body weight b.i.d 12 h),
      pazufloxacin mesylate (10 mg/kg body weight b.i.d 12 h), enrofloxacin (20 mg/kg
      body weight o.d.), and meloxicam (0.2 mg/kg body weight o.d.), respectively.
      Three other groups were co-gavaged meloxicam with above fluoroquinolones,
      respectively. These drugs were administered for 21 days. ABCG-2
      immunolocalization was mild in the retinas of control and levofloxacin-alone
      treated groups. The immunolocalization intensity was significantly higher in
      meloxicam-alone-treated group when compared to control and levofloxacin-alone
      treated groups. Immunolocalization of this transporter increased in the
      levofloxacin-meloxicam co-treated group when compared to the levofloxacin-alone
      treated group. Highest immunolocalization was observed in the enrofloxacin
      meloxicam co-treated group although the immunolocalization of all treatment
      groups, except the levofloxacin-alone-treated group, was significantly higher
      than the control and levofloxacin-alone-treated groups.

PMID- 29330818
TI  - Trace elements in four freshwater fish from a mine-impacted river: spatial
      distribution, species-specific accumulation, and risk assessment.
AB  - The concentrations of 16 elements (Mg, Al, Ca, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As,
      Sr, Cd, Ba, and Pb) were determined in four fish species (Carassius auratus,
      Squaliobarbus curriculus, Pelteobagrus fulvidraco, and Silurus asotus) collected
      in the Xiang River, a mine-impacted river in Southern China. The mean values of
      the elements analyzed in fish muscles were in the decreasing order of Mg > Ca >
      Zn > Fe > Sr > Al > Cu > Mn > Ba > As > Cr > Pb > Ni > V > Co > Cd. The
      concentrations of Mg, Ca, Sr, Ba, and Cu in omnivorous species were found to be
      significantly higher (p < 0.05) than those in carnivorous species. Negative
      correlations observed between most element concentrations and fish sizes
      indicated the younger individuals accumulated more elements than the older ones.
      Principle component analysis and orthogonal partial least squares discriminant
      analysis were employed to characterize the effects on element bioaccumulation
      using the element concentration matrix. The elemental profiles preferred to
      cluster according to differences in fish species rather than in sampling sites.
      The potential health risk evaluated through Monte Carlo simulation showed no
      appreciable adverse impact on human health from exposure to trace elements in
      fish muscles through consumption.

PMID- 29330819
TI  - Preparation of a synthetic seed for the common reed harboring an endophytic
      bacterium promoting seedling growth under cadmium stress.
AB  - Bacterial seed endophytes can facilitate germination and early plant development.
      Therefore, the introduction of seed-borne endophytes may improve selected plant
      characteristics across generations. In this study, regenerated plantlets of
      common reed (Phragmites australis) were inoculated with activated sludge to
      obtain a specific functional endophytic bacterium. Denaturing gradient gel
      electrophoresis demonstrated that abundant endophytic bacteria could be enriched
      in the roots. A siderophore-producing endophytic bacterium was isolated from the
      roots and identified as Herbaspirillum frisingense RE3-3 based on 16S rRNA
      sequences. This endophyte secrets indole-3-acetic acid to promote plant growth
      and cadmium-binding siderophores. The strain was successfully colonized into
      synthetic seeds using bacterium-propagule co-cultivation and transmitted to
      regenerated seedlings. These seedlings exhibited improved growth under cadmium
      stress. This study identifies Herbaspirillum colonization and transmission as a
      potentially valuable strategy to improve the phytotoxin resistance of reeds for
      constructed wetlands.

PMID- 29330820
TI  - Effect of ion exchange on the rate of aerobic microbial oxidation of ammonium in
      hyporheic zone sediments.
AB  - Microbially mediated ammonium oxidation is a major process affecting nitrogen
      transformation and cycling in natural environments. This study investigated
      whether ion exchange process can affect microbially mediated aerobic oxidation of
      ammonium in a hyporheic zone (HZ) sediments from the Columbia River at US
      Department of Energy's Hanford site, Washington State. Experiments were conducted
      using synthetic groundwater and river water to investigate their effect on
      ammonium oxidation. Results indicated that ammonium sorption through ion exchange
      reactions decreased the rate of ammonium oxidation, apparently resulting from the
      influence of the ion exchange on dissolved ammonium concentration, thus
      decreasing the bioavailability of ammonium for microbial oxidation. However, with
      the decrease in dissolved ammonium concentration, the sorbed ammonium released
      back to aqueous phase, and became bioavailable so that all the ammonium in the
      suspensions were oxidized. Our results implied a dynamic change in ammonium
      oxidation rates in an environment such as at HZ where river water and groundwater
      with different chemical compositions exchange frequently that can affect ammonium
      sorption and desorption through ion exchange reactions.

PMID- 29330821
TI  - Effects of ferrous sulfate amendment and water management on rice growth and
      metal(loid) accumulation in arsenic and lead co-contaminated soil.
AB  - Arsenic (As) and lead (Pb) commonly co-exist with high concentrations in paddy
      soil mainly due to human activities in south of China. This study investigates
      the effect of ferrous sulfate (FeSO4) amendment and water management on rice
      growth and arsenic (As) and lead (Pb) accumulation in rice plants. A paddy soil
      co-contaminated with As and Pb was chosen for the pot experiment with three FeSO4
      levels (0, 0.25, and 1%, on a dry weight basis) and two water managements
      (flooded, non-flooded). The concentrations of As and Pb in iron plaques and rice
      plants were determined. Application of FeSO4 and non-flooded conditions
      significantly accelerated the growth of rice plants. With the addition of FeSO4,
      iron plaques were significantly promoted and most of the As and Pb were
      sequestered in the iron plaques. The addition of 0.25% FeSO4 and non-flooded
      conditions did not significantly change the accumulation of As and Pb in rice
      grains. The practice also significantly decreased the translocation factor (TF)
      of As and Pb from roots to above-ground parts which might have been aided by the
      reduction of As and Pb availability in soil, the preventing effect of rice roots,
      and the formation of more reduced glutathione (GSH). Flooded conditions decreased
      the Pb concentration in rice plants, but increased As accumulation. Moreover,
      rice grew thin and weak and even died under flooded conditions. Overall, an
      appropriate FeSO4 dose and non-flooded conditions might be feasible for rice
      cultivation, especially addressing the As issue in the co-contaminated soil.
      However, further detailed studies to decrease the accumulation of Pb in edible
      parts and the field application in As and Pb co-contaminated soil are
      recommended.

PMID- 29330822
TI  - Biochemical changes in mussels submitted to different time periods of air
      exposure.
AB  - Intertidal species face multiple stressors on a daily basis due to their
      particular habitat. The submergence at high tide in the aquatic environment and
      emergence at low tide to the aerial environment, associated with a wide variation
      of abiotic parameters, along with anthropogenic contamination are some of the
      daily stresses that these organisms are exposed to. With such a dynamic
      environment, organisms developed strategies that allow them to avoid or tolerate
      these stressors. Among these species, bivalves are some of the most hypoxia
      tolerant, being commonly used as a biomonitoring tool due to their capacity to
      accumulate pollutants from the environment and reflect the imposed toxic impacts.
      However, when evaluating the response ability of organisms to different stressors
      under laboratory conditions, it is not common to consider the fact that exposure
      to tides can act as a confounding factor. The present study assessed the effects
      of air exposure on the biochemical (metabolic capacity, energy reserves, and
      oxidative stress related biomarkers) performance of intertidal Mytilus
      galloprovincialis mussels. Specimens of M. galloprovincialis were submitted once
      every 24 h to different periods of air exposure (3 and 6 h) for 14 days, under
      constant air and seawater temperature (19 +/- 1  degrees C). Results obtained
      revealed that air exposure can cause biochemical changes in mussels. The present
      findings demonstrated that individuals exposed to air induced superoxide
      dismutase (SOD) and catalase (CAT) activity as mechanisms to withstand the
      abiotic changes while mobilizing lipid content as the principal source of energy,
      and increasing protein content possibly as a result of an increase in the number
      of antioxidant defense enzymes. Moreover, individuals under air exposure suffered
      higher oxidative damage while showing higher metabolic rate. Results demonstrated
      that longer periods of air exposure induced more injuries, since individuals
      emerged during 6 h presented higher oxidative stress than individuals under 3 h
      of air exposure.

PMID- 29330824
TI  - Colonic fistula caused by remaining inflow cannula 14 years after left
      ventricular assist device explantation.
AB  - Intestinal complication associated with left ventricular assist device (LVAD)
      implantation is not rare, and sometimes results in serious condition of patients,
      if occurred. We report a rare case in which remaining foreign body after LVAD
      explantation resulted in colonic fistula 14 years after LVAD explantation.

PMID- 29330823
TI  - Metal Concentrations in Tissues of Gadwall and Common Teal from Miankaleh and
      Gomishan International Wetlands, Iran.
AB  - Miankaleh and Gomishan International Wetlands are important wintering areas for
      waterbirds in the Caspian Sea region. Previous studies revealed increased
      exposure to metals in some species of waterbirds using these wetlands. In this
      study, we examined concentrations of cadmium (Cd), chromium (Cr), iron (Fe), lead
      (Pb), and zinc (Zn) in kidneys, liver, and pectoral muscle of wintering Gadwall
      (Anas strepera) and Common Teal (Anas crecca) collected in 2012. In addition, we
      measured concentrations of these elements in water and sediments from the
      collection sites. The genders differed in only one element/tissue combination,
      i.e., concentrations of Fe were greater in the livers of males. Concentrations of
      elements observed in Gadwall were generally higher than in Common Teal; only
      renal Cr and muscle Zn did not differ between species. Mean Cd concentrations in
      Gadwall exceeded background levels, reaching 1.94 MUg/g ww in kidneys and 1.09
      MUg/g ww in liver. Similarly, Pb concentrations in Gadwall were also elevated
      (4.14 MUg/g ww in kidneys, 3.22 MUg/g ww in liver). Concentrations of other
      metals were within ranges commonly found in waterfowl. Concentrations of elements
      in the environment were elevated above background and comparable with the data
      obtained for this region by other scientists. However, these levels were deemed
      to not be great enough to pose an acute health risk to waterfowl. Given increased
      concentrations of some metals in duck tissues, further inquiry into the source of
      the exposure is needed for this area.

PMID- 29330825
TI  - Poststimulation time interval-dependent effects of motor cortex anodal tDCS on
      reaction-time task performance.
AB  - Anodal transcranial direct current stimulation (tDCS) induces long-term
      potentiation-like plasticity, which is associated with long-lasting effects on
      different cognitive, emotional, and motor performances. Specifically, tDCS
      applied over the motor cortex is considered to improve reaction time in simple
      and complex tasks. The timing of tDCS relative to task performance could
      determine the efficacy of tDCS to modulate performance. The aim of this study was
      to compare the effects of a single session of anodal tDCS (1.5 mA, for 15 min)
      applied over the left primary motor cortex (M1) versus sham stimulation on
      performance of a go/no-go simple reaction-time task carried out at three
      different time points after tDCS-namely, 0, 30, or 60 min after stimulation.
      Performance zero min after anodal tDCS was improved during the whole course of
      the task. Performance 30 min after anodal tDCS was improved only in the last
      block of the reaction-time task. Performance 60 min after anodal tDCS was not
      significantly different throughout the entire task. These findings suggest that
      the motor cortex excitability changes induced by tDCS can improve motor
      responses, and these effects critically depend on the time interval between
      stimulation and task performance.

PMID- 29330828
TI  - Endorsement of the HerniaSurge guidelines by the Australasian Hernia Society.

PMID- 29330829
TI  - Endorsement of the HerniaSurge guidelines by the Americas Hernia Society.

PMID- 29330826
TI  - Antibody response to polyomavirus primary infection: high seroprevalence of
      Merkel cell polyomavirus and lymphoid tissue involvement.
AB  - Human polyomaviruses (HPyVs) asymptomatically infect the human population
      establishing latency in the host, and their seroprevalence can reach 90% in
      healthy adults. Few studies have focused on the pediatric population, and there
      are no reports regarding the seroprevalence of all the newly isolated HPyVs among
      Italian children. Therefore, we investigated the frequency of serum antibodies
      against 12 PyVs in 182 immunocompetent children from Northeast Italy, by means of
      a multiplex antibody detection system. Additionally, secondary lymphoid tissues
      were collected to analyze the presence of HPyV DNA sequences using a specific
      real-time PCRs or PCRs. Almost 100% of subjects were seropositive for at least
      one PyV. Seropositivity ranged from 3% for antibodies against simian virus 40
      (SV40) in children from 0 to 3 years, to 91% for antibodies against WU
      polyomavirus (WUPyV) and HPyV10 in children from 8 to 17 years. The mean number
      of PyV for which children were seropositive increased with the increasing of age:
      4 standard deviations (SD) 1.8 in the 0-3-year group, 5 (SD 1.9) in the 4-7-year
      group, and 6 (SD 2.2) in the 8-17-year group. JC polyomavirus (JCPyV) DNA was
      detected in 1% of the adenoids, WUPyV in 12% of the tonsils, and 28% of the
      adenoids, and Merkel cell polyomavirus (MCPyV) was present in 6 and 2% of the
      tonsils and adenoids, respectively. Our study gives new insights on the
      serological evidence of exposure to PyVs during childhood, and on their possible
      respiratory route of transmission.

PMID- 29330830
TI  - Endorsement of the HerniaSurge guidelines by the Afro Middle East Hernia Society.

PMID- 29330827
TI  - Profiling Online Poker Players: Are Executive Functions Correlated with Poker
      Ability and Problem Gambling?
AB  - Poker playing and responsible gambling both entail the use of the executive
      functions (EF), which are higher-level cognitive abilities. This study
      investigated if online poker players of different ability showed different
      performances in their EF and if so, which functions were the most discriminating
      for their playing ability. Furthermore, it assessed if the EF performance was
      correlated to the quality of gambling, according to self-reported questionnaires
      (PGSI, SOGS, GRCS). Three poker experts evaluated anonymized poker hand history
      files and, then, a trained professional administered an extensive
      neuropsychological test battery. Data analysis determined which variables of the
      tests correlated with poker ability and gambling quality scores. The highest
      correlations between EF test results and poker ability and between EF test
      results and gambling quality assessment showed that mostly different clusters of
      executive functions characterize the profile of the strong(er) poker player and
      those ones of the problem gamblers (PGSI and SOGS) and the one of the cognitions
      related to gambling (GRCS). Taking into consideration only the variables
      overlapping between PGSI and SOGS, we found some key predictive factors for a
      more risky and harmful online poker playing: a lower performance in the emotional
      intelligence competences (Emotional Quotient inventory Short) and, in particular,
      those grouped in the Intrapersonal scale (emotional self-awareness,
      assertiveness, self-regard, independence and self-actualization).

PMID- 29330831
TI  - Endorsement of the HerniaSurge guidelines by the International Endohernia
      Society.

PMID- 29330832
TI  - Endorsement of the HerniaSurge guidelines by the Asia Pacific Hernia Society.

PMID- 29330833
TI  - Endorsement of the HerniaSurge guidelines by the European Association of
      Endoscopic Surgery.

PMID- 29330834
TI  - Endorsement of the Herniasurge guidelines by the European Hernia Society.

PMID- 29330837
TI  - Computer simulated modeling of healthy and diseased right ventricular and
      pulmonary circulation.
AB  - We have previously developed a simulated cardiovascular physiology model for in
      silico testing and validation of novel closed-loop controllers. To date, a
      detailed model of the right heart and pulmonary circulation was not needed, as
      previous controllers were not intended for use in patients with cardiac or
      pulmonary pathology. With new development of controllers for vasopressors, and
      looking forward, for combined vasopressor-fluid controllers, modeling of right
      sided and pulmonary pathology is now relevant to further in-silico validation, so
      we aimed to expand our existing simulation platform to include these elements.
      Our hypothesis was that the completed platform could be tuned and stabilized such
      that the distributions of a randomized sample of simulated patients' baseline
      characteristics would be similar to reported population values. Our secondary
      outcomes were to further test the system in representing acute right heart
      failure and pulmonary artery hypertension. After development and tuning of the
      right-sided circulation, the model was validated against clinical data from
      multiple previously published articles. The model was considered 'tuned' when
      100% of generated randomized patients converged to stability (steady,
      physiologically-plausible compartmental volumes, flows, and pressures) and
      'valid' when the means for the model data in each health condition were contained
      within the standard deviations for the published data for the condition. A fully
      described right heart and pulmonary circulation model including non-linear
      pressure/volume relationships and pressure dependent flows was created over a 6
      month span. The model was successfully tuned such that 100% of simulated patients
      converged into a steady state within 30 s. Simulation results in the healthy
      state for central venous volume (3350 +/- 132 ml) pulmonary blood volume (405 +/-
      39 ml), pulmonary artery pressures (systolic 20.8 +/- 4.1 mmHg and diastolic 9.4
      +/- 1.8 mmHg), left atrial pressure (4.6 +/- 0.8 mmHg), PVR (1.0 +/- 0.2 wood
      units), and CI (3.8 +/- 0.5 l/min/m2) all met criteria for acceptance of the
      model, though the standard deviations of LAP and CI were somewhat narrower than
      published comparators. The simulation results for right ventricular infarction
      also fell within the published ranges: pulmonary blood volume (727 +/- 102 ml),
      pulmonary arterial pressures (30 +/- 4 mmHg systolic, 12 +/- 2 mmHg diastolic),
      left atrial pressure (13 +/- 2 mmHg), PVR (1.6 +/- 0.3 wood units), and CI (2.0
      +/- 0.4 l/min/m2) all fell within one standard deviation of the reported
      population values and vice-versa. In the pulmonary hypertension model, pulmonary
      blood volume of 615 +/- 90 ml, pulmonary arterial pressures of 80 +/- 14 mmHg
      systolic, 36 +/- 7 mmHg diastolic, and the left atrial pressure of 11 +/- 2 mmHg
      all met criteria for acceptance. For CI, the simulated value of 2.8 +/- 0.4
      l/min/m2 once again had a narrower spread than most of the published data, but
      fell inside of the SD of all published data, and the PVR value of 7.5 +/- 1.6
      wood units fell in the middle of the four published studies. The right
      ventricular and pulmonary circulation simulation appears to be a reasonable
      approximation of the right-sided circulation for healthy physiology as well as
      the pathologic conditions tested.

PMID- 29330836
TI  - Pathogenesis of non-alcoholic fatty liver disease mediated by YAP.
AB  - OBJECTIVE: This study aimed to investigate the mechanism of the interaction
      between Yes-associated protein (YAP) and transforming growth factor-beta (TGF
      beta)/Smad signaling pathways in the development of non-alcoholic fatty liver
      disease (NAFLD). METHODS: Serum samples of monkeys with biopsy-proven NAFLD and
      healthy normal monkeys were used to measure fasting plasma glucose (FPG), low
      density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride (TG) and
      albumin (ALB) with the BECKMAN CX5 PRO. Hematoxylin-eosin staining (H&E) was used
      for pathologic analysis, Masson trichrome staining was used to assess for
      fibrosis staging, and Oil Red O staining was used to detect lipid droplet
      deposition. According to an NAFLD activity score of < 4 points and > 4 points,
      the samples were divided into groups: the steatosis group and fibrosing NASH
      group. Furthermore, monkeys with a fibrosis stage < 2 were assigned to the mild
      fibrosis group, while monkeys with fibrosis stage >= 2 were assigned to the
      significant fibrosis group. Moreover, the fibrosis stage was subdivided as
      follows: stages 1a, 1c and 2-3. Immunohistochemistry and real-time quantitative
      PCR were used to quantify protein and gene expression, respectively. RESULTS: In
      the present study, 54 monkeys with NAFLD and 23 normal monkeys were recruited.
      Serum FPG and TG levels were higher in fibrosing NASH monkeys compared with
      simple steatosis and normal monkeys, and differences between simple steatosis and
      normal monkeys were not statistically significant (p > 0.05). YAP increased in
      NAFLD, which mainly localized in the nuclei of hepatocytes, perivascular cells
      and bile duct cells; the accumulation of YAP correlated with the severity of
      hepatocyte injury. Compared with normal monkeys, the expression of TGF-beta,
      alpha-smooth muscle actin (alpha-SMA), Drosophila mothers against decapentaplegic
      protein 3 (Smad3) and connective tissue growth factor (CTGF) in the liver of
      simple steatosis monkeys significantly increased (p < 0.01). Compared with simple
      steatosis monkeys, the expression of TGF-beta, alpha-SMA, Smad3 and CTGF in
      fibrosing NASH significantly increased (p < 0.01). However, the expression of
      Drosophila mothers against decapentaplegic protein 7 (Smad7) in the liver of
      fibrosing NASH monkeys significantly decreased (p < 0.01). With the severity of
      liver fibrosis, the expression of TGF-beta, alpha-SMA, Smad3 and CTGF gradually
      increased, and the difference was statistically significant (p < 0.01). However,
      there was no significant difference in the expression of Smad3 between fibrosis
      stage 1a and 1c. Compared with normal monkeys, the expression of Smad7 in the
      liver of monkeys with fibrosis significantly decreased (p < 0.01), but was
      significantly higher at fibrosis stage 1c than at fibrosis stage 1a and 2.
      CONCLUSION: The YAP and TGF-beta signaling pathways and the interaction between
      them promote the development and progression of NAFLD.

PMID- 29330838
TI  - The potential impact of multidimesional geriatric assessment in the social
      security system.
AB  - AIM: To evaluate the efficacy of multidimensional geriatric assessment (MGA/CGA)
      in patients over 65 years old in predicting the release of the accompaniment
      allowance (AA) indemnity by a Local Medico-Legal Committee (MLC-NHS) and by the
      National Institute of Social Security Committee (MLC-INPS). METHODS: In a
      longitudinal observational study, 200 Italian elder citizens requesting AA were
      first evaluated by MLC-NHS and later by MLC-INPS. Only MLC-INPS performed a
      MGA/CGA (including SPMSQ, Barthel Index, GDS-SF, and CIRS). This report was
      written according to the STROBE guidelines. RESULTS: The data analysis was
      performed on January 2016. The evaluation by the MLC-NHS and by the MLC-INPS was
      in agreement in 66% of cases. In the 28%, the AA benefit was recognized by the
      MLC-NHS, but not by the MLC-INPS. By the multivariate analysis, the best
      predictors of the AA release, by the MLC-NHS, were represented by gender and the
      Barthel Index score. The presence of carcinoma, the Barthel Index score, and the
      SPMQ score were the best predictors for the AA release by MLC-INPS. CONCLUSIONS:
      MGA/CGA could be useful in saving financial resources reducing the risk of
      incorrect indemnity release. It can improve the accuracy of the impairment
      assessment in social security system.

PMID- 29330840
TI  - Clinical assessment of class II resin-based composites versus preformed metal
      crowns performed on primary molars in patients at high risk of caries.
AB  - AIM: To compare class II resin composite with preformed metal crowns (PMC) in the
      treatment of proximal dentinal caries in high caries-risk patients. METHODS: The
      charts (270) of paediatric patients with proximal caries of their primary molars
      were reviewed. Success or failure of a procedure was assessed using the dental
      notes. Survival analysis was used to calculate the mean survival time (MST) for
      both procedures. The influence of variables on the mean survival time was
      investigated. RESULTS: A total of 593 class II resin composites and 243 PMCs were
      placed in patients ranging between 4-13 years of age. The failure percentage of
      class II resin composites was 22.6% with the majority having been due to
      recurrent caries, while the failure percentage of PMCs was 15.2% with the
      majority due to loss of the crown. There was no significant difference between
      the MST of class II resin composites and PMCs, 41.3 and 45.6 months respectively
      (p value = 0.06). In class II resin composites, mesial restorations were
      associated with lower MST compared to distal restorations (p-value < 0.001).
      CONCLUSIONS: The MST of resin composites and PMCs were comparable when performed
      on high caries-risk patients.

PMID- 29330841
TI  - Delayed replantation of an avulsed immature permanent incisor and apexification
      using a novel fast-setting calcium silicate cement containing fluoride: a 3-year
      follow-up case report.
AB  - BACKGROUND: Traumatic tooth avulsion requires an urgent intervention to replant
      the tooth. Prolonged post-injury dry extra-oral conditions worsen the prognosis
      and increase the risk of root resorption. Fluoride has the potential to delay
      replacement resorption. Calcium silicate cements (CSC) are used to seal the root
      canal system and to stimulate periapical regeneration in immature open apex teeth
      (apexification). This report suggests the application of a novel fast-setting CSC
      with fluoride for apexification in an attempt to hinder root resorption. CASE
      REPORT: A delayed replantation of an avulsed open apex permanent central incisor
      after 75 h of storage in a dry condition in a 6-year-old girl. Standard treatment
      guidelines for avulsed immature permanent teeth were followed. After tooth
      replantation a novel fast-setting, CSC containing fluoride was used for
      apexification. FOLLOW-UP: The radiographic and clinical evaluations over a period
      of 3 years demonstrated periodontal bone healing without root resorption,
      mobility, and ankylosis and an acceptable periapical tissue tolerance to the
      novel CSC. However, a longer follow-up period is needed. CONCLUSIONS: Delayed
      replantation of the avulsed open apex permanent incisor after 75 h of storage
      under dry conditions and apexification with a novel fast-setting CSC showed a
      successful outcome after 3 years. Novel CSC with fluoride demonstrated an
      acceptable biocompatibility and tissue tolerance.

PMID- 29330843
TI  - Clinical guideline and recommendations on pre-operative exercise training in
      patients awaiting major non-cardiac surgery.
AB  - Despite calls for the routine implementation of pre-operative exercise programmes
      to optimise patient fitness before elective major surgery, there is no practical
      guidance for providing safe and effective exercise in this specific context. The
      following clinical guideline was developed following a review of the evidence on
      the effects of pre-operative exercise interventions. We developed a series of
      best-practice and, where possible, evidence-based statements to advise on patient
      care with respect to exercise training in the peri-operative period. These
      statements cover: patient selection for exercise training in surgical patients;
      integration of exercise training into multi-modal prehabilitation programmes; and
      advice on exercise prescription factors and follow-up. Although we acknowledge
      that further research is needed to identify the optimal exercise prescription in
      different clinical scenarios, we urge peri-operative teams to make use of these
      recommendations.

PMID- 29330842
TI  - Self-perceived long-term transfer of learning after postpartum hemorrhage
      simulation training.
AB  - OBJECTIVE: To explore long-term transfer (application of acquired knowledge and
      skills on the job) after postpartum hemorrhage simulation training based on
      either instructional design (ID) principles or conventional best practice.
      METHODS: In this qualitative study, semi-structured interviews with obstetrics
      and gynecology healthcare practitioners were conducted between August 7 and
      September 26, 2015, in Recife, Brazil. The participants were randomly selected
      from each of two postpartum hemorrhage simulations attended 2 years earlier (one
      ID and one conventional best practice). Thematic analysis was used to explore (1)
      residents' perceptions of long-term transfer of learning, (2) ID elements
      influencing the perceived long-term transfer, and (3) differences in the
      participants' perceptions according to the type of simulation attended. RESULTS:
      There were 12 interview participants. After either simulation format, residents
      perceived long-term transfer effects. Training design factors influencing
      transfer were, in their opinion, related to trainees' characteristics, simulation
      design, and workplace environment. Trainees who participated in the ID-based
      simulation perceived better communication skills and better overall situational
      awareness: "I didn't do that before." CONCLUSION: All residents perceived long
      term transfer after simulation training for postpartum hemorrhage. Those who
      attended the ID format additionally perceived improvements in communication
      skills and situational awareness, which are fundamental factors in the management
      of postpartum hemorrhage.

PMID- 29330839
TI  - Peripheral Blood Brain-Derived Neurotrophic Factor as a Biomarker of Alzheimer's
      Disease: Are There Methodological Biases?
AB  - Mounting evidence that alterations in brain-derived neurotrophic factor (BDNF)
      levels and signaling may be involved in the etiopathogenesis of Alzheimer's
      disease (AD) has suggested that its blood levels could be used as a biomarker of
      the disease. However, higher, lower, or unchanged circulating BDNF levels have
      all been described in AD patients compared to healthy controls. Although the
      reasons for such different findings are unclear, methodological issues are likely
      to be involved. The heterogeneity of participant recruitment criteria and the
      lack of control of variables that influence circulating BDNF levels regardless of
      dementia (depressive symptoms, medications, lifestyle, lack of overlap between
      serum and plasma, and experimental aspects) are likely to bias result and prevent
      study comparability. The present work reviews a broad panel of factors, whose
      close control could help reduce the inconsistency of study findings, and offers
      practical advice on their management. Research directed at elucidating the weight
      of each of these variables and at standardizing analytical methodologies is
      urgently needed.

PMID- 29330844
TI  - Bradykinin mediates the association of collecting duct cells to form migratory
      colonies, through B2 receptor activation.
AB  - It is known that bradykinin (BK) B2 receptor (B2R) is expressed in the collecting
      duct (CD) cells of the newborn rat kidney, but little is known about its role
      during early postnatal life. Therefore, we hypothesize that BK could participate
      in the mechanisms that mediate CD formation during the postnatal renal
      development. Performing primary cultures, combined with biochemical,
      immunocytochemical, and time-lapse analysis, we studied the role of BK in CD cell
      behavior isolated from renal papilla of neonatal rats. A reverse relationship was
      observed between B2R expression and the degree of CD epithelial cell sheet
      maturation. BK stimulation induced CD cell association upon B2R activation. The
      lack of B2R expression in cells showing mature adherens junctions suggested that
      BK is mostly involved in early adhesive events, thus favoring the initial
      formation of CD during development. Time-lapse analysis revealed that BK induced
      a high protrusive activity of CD cells, denoted by ruffle formation and
      lamellipodia extension. PI3K was involved in the BK-induced CD cell-cell
      association and the acquisition of the migratory phenotype since, when inhibited,
      membrane ruffles, and filopodia between cells diminished. Results indicate that
      the actions of BK mediated by PI3K activation were due to the downstream Akt and
      Rac pathways. This study, performed with CD cells that were not genetically
      manipulated, provides new experimental evidence supporting a novel role of BK in
      rat renal CD organization. As B2R blockade results in abnormal tubular
      differentiation, our results contribute to better understanding the etiology of
      human congenital renal malformation and diseases.

PMID- 29330846
TI  - Oral propranolol for infantile haemangioma may be associated with transient gross
      motor delay.

PMID- 29330847
TI  - Interchangeability of Generic Drugs: A Nonparametric Pharmacokinetic Model of
      Gabapentin Generic Drugs.
AB  - Substitution by generic drugs is allowed when bioequivalence to the originator
      drug has been established. However, it is known that similarity in exposure may
      not be achieved at every occasion for all individual patients when switching
      between formulations. The ultimate aim of our research is to investigate if
      pharmacokinetic subpopulations exist when subjects are exposed to bioequivalent
      formulations. For that purpose, we developed a pharmacokinetic model for
      gabapentin, based on data from a previously conducted bioavailability study
      comparing gabapentin exposure following administration of the gabapentin
      originator and three generic gabapentin formulations in healthy subjects. Both
      internal and external validation confirmed that the optimal model for description
      of the gabapentin pharmacokinetics in this comparative bioavailability study was
      a two-compartment model with absorption constant, an absorption lag time, and
      clearance adjusted for renal function, in which each model parameter was
      separately estimated per administered formulation.

PMID- 29330848
TI  - Cultured allogeneic fibroblast injection vs. fibroblasts cultured on amniotic
      membrane scaffold for dystrophic epidermolysis bullosa treatment.
AB  - BACKGROUND: Different methods of fibroblast application have been examined to
      treat recessive dystrophic epidermolysis bullosa (RDEB). OBJECTIVES: To compare
      the effects of intradermal injection of cultured allogeneic fibroblasts in
      healing RDEB wounds with those of fibroblasts seeded on amniotic membrane
      scaffolds (FAMS) or standard wound care (SWC) with Vaseline(r) gauze as controls.
      METHODS: Seven patients were recruited, and seven wounds were assessed in each
      patient: three wounds were treated with injection of intradermal fibroblasts,
      three were treated with FAMS and one was dressed with SWC. Changes in wound size
      were assessed after 2 and 12 weeks of treatment. Qualitative wound scores (QWS)
      were used to assess wound severity. Additionally, biopsies and antigen mapping
      were performed to detect type VII collagen in the dermoepidermal junction.
      RESULTS: In both treated areas, the QWS and wound size were significantly
      decreased (P < 0.001), whereas there were no changes in the control group (P =
      0.29). After 2 and 12 weeks of treatment, the wound size was significantly
      decreased in wounds that were treated with fibroblast injection compared with
      those treated with FAMS (P < 0.001); but no significant changes were found in the
      control group. CONCLUSIONS: Fibroblast injection has been shown to promote
      healing of RDEB wounds and is superior to FAMS or the control treatment.

PMID- 29330849
TI  - Expression of YAP and TAZ in molluscum contagiosum virus infected skin.

PMID- 29330850
TI  - How I Do It: Examining the value of an otology multidisciplinary team meeting.

PMID- 29330845
TI  - The association between smoking and cancer incidence in BRCA1 and BRCA2 mutation
      carriers.
AB  - Tobacco smoke is an established carcinogen, but the association between tobacco
      smoking and cancer risk in BRCA mutation carriers is not clear. The aim of this
      study was to evaluate prospectively the association between tobacco smoking and
      cancer incidence in a cohort of BRCA1 and BRCA2 mutation carriers. The study
      population consisted of unaffected BRCA mutation carriers. Information on
      lifestyle including smoking histories, reproductive factors, and past medical
      histories was obtained through questionnaires. Incident cancers were updated
      biennially via follow-up questionnaires. Hazard ratios (HRs) and 95% confidence
      intervals (CIs) were estimated using time-dependent Cox regression models. There
      were 700 incident cancers diagnosed over 26,711 person-years of follow-up. The
      most frequent cancers seen in BRCA mutation carriers were breast (n = 428; 61%)
      and ovarian (n = 109; 15%) cancer. Compared to nonsmokers, (ever) smoking was
      associated with a modest increased risk of all cancers combined (HR = 1.17; 95%CI
      1.01-1.37). Women in the highest group of total pack-years (4.3-9.8) had an
      increased risk of developing any cancer (HR = 1.27; 95%CI 1.04-1.56), breast
      cancer (HR = 1.33, 95%CI 1.02-1.75), and ovarian cancer (HR = 1.68; 95%CI 1.06
      2.67) compared to never smokers. The associations between tobacco smoking and
      cancer did not differ by BRCA mutation type or by age at diagnosis. This
      prospective study suggests that tobacco smoking is associated with a modest
      increase in the risks of breast and ovarian cancer among women with BRCA1 or
      BRCA2 mutation.

PMID- 29330851
TI  - A case of xeroderma pigmentosum complementation group C with diverse clinical
      features.

PMID- 29330852
TI  - Characteristics and intestinal immunomodulating activities of water-soluble
      pectic polysaccharides from Chenpi with different storage periods.
AB  - BACKGROUND: The traditional view considers that Chenpi (dried citrus peel) stored
      over the long-term has better health efficacies compared to fresh Chenpi,
      although the detailed mechanism responsible for this remains obscure. RESULTS:
      The three water-soluble pectic polysaccharides (CPP1, CPP5 and CPP10) were
      obtained from 1-, 5- and 10-year Chenpi, respectively, and their physicochemical
      characteristics and intestinal immunomodulating activities were investigated and
      compared. The results obtained showed that CPP5 and CPP10 demonstrated a lower
      dynamic viscosity and degree of methylesterification, as well as a higher
      molecular heterogeneity, compared to CPP1. Monosaccharide composition analysis
      indicated that CPP1 was composed of arabinose, galacturonic acid and galactose,
      and a small amount of rhamnose; however, CPP5 and CPP10 consisted of arabinose,
      galacturonic acid, galactose, glucose and xylose, and a small amount of rhamnose.
      With the extension of storage period of Chenpi, the content of soluble conjugate
      phenolic acids increased in the pectic polysaccharide. Furthermore, it was
      confirmed that the pectic polysaccharides extracted from the 5-year and 10-year
      Chenpi could significantly enhance the proliferation of bone marrow cells via
      activating the Peyer's patch cells in vitro. CONCLUSION: The present study
      demonstrates the differences in the pectic polysaccharides from Chenpi with
      different storage periods and also confirms that the pectic polysaccharides
      extracted from Chenpi stored over the long-term had more significant intestinal
      activities compared to that obtained from the fresh Chenpi. This phenomenon might
      partly explain why the Chenpi stored over the long-term has better healthcare
      effects. (c) 2018 Society of Chemical Industry.

PMID- 29330853
TI  - Transnasal humidified rapid-insufflation ventilatory exchange (THRIVE) vs.
      facemask breathing pre-oxygenation for rapid sequence induction in adults: a
      prospective randomised non-blinded clinical trial.
AB  - Transnasal humidified rapid-insufflation ventilatory exchange (THRIVE) can
      prolong apnoea time in adults. Therefore, THRIVE used for pre-oxygenation in
      rapid sequence induction of anaesthesia could extend safe apnoea time during
      prolonged laryngoscopy and intubation. In this randomised controlled trial, we
      compared the lowest peripheral oxygen saturation (SpO2 ) during intubation when
      pre-oxygenating with either traditional facemask or THRIVE. Eighty adult
      patients, undergoing rapid sequence induction of anaesthesia for emergency
      surgery, were randomly allocated to pre-oxygenation with 100% oxygen with
      facemask or with THRIVE. Median (IQR [range]) lowest SpO2 until 1 min after
      intubation was 99% (97-100 [70-100]%) for the facemask group vs. 99% (99-100 [96
      100]%) for the THRIVE group (p = 0.097). Five patients (12.5%) desaturated below
      93% when pre-oxygenated with the facemask vs. none in the THRIVE group (p =
      0.019). There were no differences in intubation time or apnoea time between the
      groups. Median intubation time was 51 (34-66 [22-261]) s in the facemask group
      vs. 48 (38-63 [10-146]) s in the THRIVE group (p = 0.99). Median apnoea time was
      109 (86-142 [37-291]) s and 116 (92-146 [63-249]) s when using facemask and
      THRIVE, respectively (p = 0.49). No signs of regurgitation of gastric content
      were detected. The data on desaturation indicate potential benefits of
      oxygenation with THRIVE for rapid sequence induction compared with facemask pre
      oxygenation.

PMID- 29330854
TI  - Combined spinal-epidural vs. spinal anaesthesia for caesarean section: meta
      analysis and trial-sequential analysis.
AB  - Combined spinal-epidural and single-shot spinal anaesthesia are both used for
      caesarean section. It has been claimed in individual trials that combined spinal
      epidural is associated with higher sensory spread and greater cardiovascular
      stability. We set out to gather all available evidence. We performed: a
      systematic literature search to identify randomised controlled trials comparing
      combined spinal-epidural with spinal anaesthesia for caesarean section:
      conventional meta-analysis; trial-sequential analysis; and assessment of trial
      quality using the Grading of Recommendations Assessment, Development, and
      Evaluation (GRADE) system. Fifteen trials with high heterogeneity, including 1015
      patients, were analysed. There was no significant difference between combined
      spinal-epidural and spinal anaesthesia for our primary outcomes maximum sensory
      height and vasopressor use (mg ephedrine equivalents). However, trial-sequential
      analysis suggested insufficient data and the GRADE scores showed 'very low'
      quality of evidence for these outcomes. The secondary outcomes hypotension, time
      for sensory block to recede to the level of T10, and the combined outcome of
      nausea and vomiting, did not differ significantly between the interventions. The
      block times were statistically significantly longer for combined spinal-epidural
      in individual trials, but only one trial showed a clinically meaningful
      difference (11 min). Based on this analysis, and taking into consideration all
      comparisons irrespective of whether drugs had been applied via the epidural
      route, there is not enough evidence to postulate any advantage compared with the
      spinal technique. Future analyses and studies need to examine the potential
      advantages of the combined spinal-epidural technique by using the epidural route
      intra- and/or postoperatively.

PMID- 29330855
TI  - Getting Innovative Therapies Faster to Patients at the Right Dose: Impact of
      Quantitative Pharmacology Towards First Registration and Expanding Therapeutic
      Use.
AB  - Quantitative pharmacology (QP) applications in translational medicine, drug
      development, and therapeutic use were crowd-sourced by the ASCPT Impact and
      Influence initiative. Highlighted QP case studies demonstrated faster access to
      innovative therapies for patients through 1) rational dose selection for pivotal
      trials; 2) reduced trial-burden for vulnerable populations; or 3) simplified
      posology. Critical success factors were proactive stakeholder engagement,
      alignment on the value of model-informed approaches, and utilizing foundational
      clinical pharmacology understanding of the therapy.

PMID- 29330857
TI  - Reduction of hyaluronan and increased expression of HYBID (alias CEMIP and
      KIAA1199) correlate with clinical symptoms in photoaged skin.
AB  - BACKGROUND: Hyaluronan (HA) metabolism in skin fibroblasts is mediated by HYBID
      (hyaluronan binding protein involved in hyaluronan depolymerization, alias CEMIP
      and KIAA1199) and the HA synthases HAS1 and HAS2. However, photoageing-dependent
      changes in HA and their molecular mechanisms, and the relationship between HA
      metabolism and clinical symptoms in photoaged skin remain elusive. OBJECTIVES: We
      examined the amount, size and tissue distribution of HA and expression levels of
      HYBID, HAS1 and HAS2 in photoaged skin, and analysed their relationship with the
      degree of photoageing. METHODS: Photoageing-dependent changes of HA were
      investigated by studying skin biopsies isolated from photoprotected and
      photoexposed areas of the same donors, and the relationships between HA and
      photoageing symptoms such as skin wrinkling and sagging were examined. RESULTS:
      Skin biopsy specimens showed that the amount and size of HA are decreased in
      photoexposed skin compared with photoprotected skin, and this was accompanied by
      increased expression of HYBID and decreased expression of HAS1 and HAS2.
      Histologically, HA staining in the papillary dermis was decreased in photoexposed
      skin, showing reverse correlation with HYBID expression. HYBID expression in the
      photoexposed skin directly correlated with skin roughness and sagging parameters,
      and the reduced HA staining in the papillary dermis in the photoexposed skin
      positively correlated with these symptoms. CONCLUSIONS: These data demonstrate
      that imbalance between HYBID-mediated HA degradation and HAS-mediated HA
      synthesis may contribute to enhanced HA catabolism in photoaged skin, and suggest
      that HYBID-mediated HA reduction in the papillary dermis is related to skin
      wrinkling and sagging of photoaged skin.

PMID- 29330856
TI  - Reproductive history, breast-feeding and risk of triple negative breast cancer:
      The Breast Cancer Etiology in Minorities (BEM) study.
AB  - Few risk factors have been identified for triple negative breast cancer (TNBC)
      which lacks expression of estrogen receptor (ER), progesterone receptor (PR) and
      human epidermal growth factor receptor 2 (HER2). This more aggressive subtype
      disproportionately affects some racial/ethnic minorities and is associated with
      lower survival. We pooled data from three population-based studies (558 TNBC and
      5,111 controls) and examined associations of TNBC risk with reproductive history
      and breast-feeding. We estimated odds ratios (ORs) and 95% confidence intervals
      (CIs) using multivariable logistic regression. For younger women, aged <50 years,
      TNBC risk was increased two-fold for parous women who never breast-fed compared
      to nulliparous women (OR = 2.02, 95% CI = 1.12-3.63). For younger parous women,
      longer duration of lifetime breast-feeding was associated with a borderline
      reduced risk (>=24 vs. 0 months: OR = 0.52, 95% CI = 0.26-1.04, Ptrend  = 0.06).
      Considering the joint effect of parity and breast-feeding, risk was increased two
      fold for women with >=3 full-term pregnancies (FTPs) and no or short-term (<12
      months) breast-feeding compared to women with 1-2 FTPs and breast-feeding >=12
      months (OR = 2.56, 95% CI = 1.22-5.35). None of these associations were observed
      among older women (>=50 years). Differences in reproductive patterns possibly
      contribute to the ethnic differences in TNBC incidence. Among controls aged <50
      years, the prevalence of no or short-term breast-feeding and >=3 FTPs was highest
      for Hispanics (22%), followed by African Americans (18%), Asian Americans (15%)
      and non-Hispanic whites (6%). Breast-feeding is a modifiable behavioral factor
      that may lower TNBC risk and mitigate the effect of FTPs in women under age 50
      years.

PMID- 29330858
TI  - Long-term outcomes of cochlear implantation in patients with high-frequency
      hearing loss.
AB  - OBJECTIVE: To demonstrate the long-term benefits of implantation in patients with
      high-frequency sensorineural hearing loss, this report provides 5-year follow-up
      on a group of implant recipients who were subjects of the CochlearTM Nucleus(r)
      HybridTM L24 Implant System pivotal clinical study. METHODS: The results of three
      related clinical studies were compiled to provide outcome data after 1, 3, and 5
      years of implant use in a group of subjects who presented with preoperative high
      frequency hearing loss and were implanted with a Nucleus Hybrid L24 (Cochlear
      Ltd., Sydney, Australia) cochlear implant. A subset of the 50 adult subjects (N =
      32) who participated in the Hybrid L24 pivotal Investigational Device Exemption
      (IDE) completed comprehensive evaluations at 12 months postactivation, 3 years
      postactivation, and then as part of a postapproval study at 5 years
      postactivation. Testing included audiometric, speech perception, and subjective
      satisfaction measures. RESULTS: Mean unilateral speech perception performance was
      significantly improved at all postoperative intervals compared to preoperative
      best-aided results and has remained stable to 5 years postactivation. Ninety-four
      percent of subjects had measurable hearing, and 72% continued to use electric
      acoustic stimulation in the implanted ear after 5 years of implant use.
      Subjective satisfaction results support objective performance improvements.
      CONCLUSION: Results demonstrate long-term success of patients with high-frequency
      hearing loss following Hybrid L24 (Cochlear) cochlear implantation. Benefits
      include speech perception abilities significantly better than those in the
      preoperative best-aided condition, with additional benefit in those using
      electric-acoustic stimulation in the implanted ear. LEVEL OF EVIDENCE: 2b.
      Laryngoscope, 1939-1945, 2018.

PMID- 29330859
TI  - Differential effects of phototherapy, adalimumab and betamethasone-calcipotriol
      on effector and regulatory T cells in psoriasis.
AB  - BACKGROUND: Psoriasis is a chronic T-cell-mediated skin disease with marked
      social and economic burdens. Current treatments are unsatisfactory, with
      unpredictable remission times and incompletely understood modes of action. Recent
      advances in our understanding of the pathogenesis of psoriasis have identified
      the imbalance between CD4+ T effector cells, particularly the T helper (Th)17
      subset, and regulatory T cells (Tregs) as key to the development of psoriatic
      lesions, and therefore a novel therapeutic target. OBJECTIVES: To quantify in
      patients the effects of three commonly used psoriasis treatment modalities on the
      Th1, Th2, Th17 and Treg subsets, and to test whether any change correlates with
      clinical response. METHODS: Flow cytometry was used to enumerate Th1, Th2, Th17
      and Treg subsets in blood and skin of patients with psoriasis before and after
      receiving any of the following treatments: narrowband ultraviolet B (NB-UVB),
      adalimumab and topical betamethasone-calcipotriol combination (Dovobet(r) )
      RESULTS: All patients responded clinically to the treatments. NB-UVB
      significantly increased the numbers of circulating and skin Tregs, while, by
      contrast, adalimumab reduced Th17 cells in these compartments, and Dovobet had
      dual effects by both increasing Tregs and reducing Th17 cells. CONCLUSIONS: The
      differential effects reported here for the above-mentioned treatment modalities
      could be exploited to optimize or design therapeutic strategies to overcome the
      inflammatory drivers more effectively and restore the Th17-Treg balance in
      psoriasis.

PMID- 29330860
TI  - Sudden death in sport and riding horses during and immediately after exercise: A
      case series.
AB  - BACKGROUND: Sudden death affects the health of horses, the safety of riders and
      the public perception of animal welfare during equestrian events. OBJECTIVES: To
      describe the signalment, clinical history, sudden death episode, rider injuries
      and causes of sudden death during exercise or closely thereafter in sport and
      pleasure riding horses. STUDY DESIGN: Retrospective case series based on an
      online questionnaire. METHODS: An online questionnaire was distributed to the
      veterinary and equestrian community. Connections of animals reported in the press
      to have died suddenly were sent the survey. Responses were analysed to obtain
      information. RESULTS: Fifty-seven cases met inclusion criteria with enough
      information to be analysed. The most common discipline was eventing (n = 23,
      40.4%), and the most common breed involved was Thoroughbred (n = 23, 40.4%).
      Forty-one (71.9%) horses collapsed during exercise, and 16 (28.1%) shortly
      thereafter. Twenty-four (42.1%) horses died during or near the time of
      competition and 33 (57.9%) during or near the time of training or a pleasure
      ride. In 16 (28.1%) horses, the cause of death was known or strongly suspected
      based on a post-mortem result, and a cardiovascular origin was reported in 13 of
      these 16 cases. Riders were injured in 13 (22.8%) cases, and injuries to their
      extremities were the most frequent. MAIN LIMITATIONS: There is potential for
      misdiagnosis and recall and selection bias, and in the absence of data on the
      total number of horses engaged in equestrian sports and riding, prevalence cannot
      be calculated. CONCLUSIONS: Sudden death occurred in many types of equestrian
      sports and in riding horses. Death outside competition was more common suggesting
      that registries based on reports from official veterinarians underestimate the
      magnitude of this problem. Rider injuries were not uncommon when ridden horses
      collapsed and died. A definitive diagnosis for the cause of death was not
      commonly achieved and cardiovascular origin was the most common where a diagnosis
      was proposed by survey respondents.

PMID- 29330861
TI  - Validity evidence as a key marker of quality of technical skill assessment in OTL
      HNS.
AB  - OBJECTIVE: Quality monitoring of assessment practices should be a priority in all
      residency programs. Validity evidence is one of the main hallmarks of assessment
      quality and should be collected to support the interpretation and use of
      assessment data. Our objective was to identify, synthesize, and present the
      validity evidence reported supporting different technical skill assessment tools
      in otolaryngology-head and neck surgery (OTL-HNS). METHODS: We performed a
      secondary analysis of data generated through a systematic review of all published
      tools for assessing technical skills in OTL-HNS (n = 16). For each tool, we coded
      validity evidence according to the five types of evidence described by the
      American Educational Research Association's interpretation of Messick's validity
      framework. Descriptive statistical analyses were conducted. RESULTS: All 16 tools
      included in our analysis were supported by internal structure and relationship to
      variables validity evidence. Eleven articles presented evidence supporting
      content. Response process was discussed only in one article, and no study
      reported on evidence exploring consequences. CONCLUSION: We present the validity
      evidence reported for 16 rater-based tools that could be used for work-based
      assessment of OTL-HNS residents in the operating room. The articles included in
      our review were consistently deficient in evidence for response process and
      consequences. Rater-based assessment tools that support high-stakes decisions
      that impact the learner and programs should include several sources of validity
      evidence. Thus, use of any assessment should be done with careful consideration
      of the context-specific validity evidence supporting score interpretation, and we
      encourage deliberate continual assessment quality-monitoring. LEVEL OF EVIDENCE:
      NA. Laryngoscope, 128:2296-2300, 2018.

PMID- 29330862
TI  - Dermatomyositis: Histopathologic findings of parakeratosis and dermal edema
      revisited.
AB  - The cutaneous manifestations of dermatomyositis range from classical in the case
      of heliotrope rash and Gottron papules to less common papulosquamous and
      edematous/vesiculobullous lesions; histopathologic descriptions are dominated by
      interface dermatitis. We present a case of dermatomyositis with a combination of
      common and rare skin findings, both clinically and histologically. Increased
      awareness of papulosquamous and edematous lesions of dermatomyositis can help
      direct patient care. Although uncommon, confluent parakeratosis and dermal edema
      can be manifestations of dermatomyositis.

PMID- 29330864
TI  - Allergy-Committed to progress in allergy and immunology.

PMID- 29330863
TI  - Hyoepiglottic ligament collagen and elastin fiber composition and changes
      associated with aging.
AB  - OBJECTIVE: The epiglottis may contribute to upper airway obstruction in
      approximately 10% of patients with obstructive sleep apnea. Clinical experience
      indicates that older patients may be more likely to have epiglottis-related
      obstruction. This study was designed to examine tissue characteristics of the
      hyoepiglottic ligament as a possible factor in epiglottis-related obstruction
      based on previous research suggesting that older adults have fewer collagen,
      elastin, and muscle fibers in the hyoepiglottic ligament. METHODS: This is a
      cross-sectional study of 25 human cadaver hyoepiglottic ligaments. Specimens were
      stained using Masson's trichrome and Picrosirius red for collagen fibers and with
      Verhoeff-Van Gieson for elastin fibers. Percentage of collagen and elastin fiber
      staining for each specimen was calculated and averaged over three regions of each
      ligament section. Regression analysis was used to determine the association
      between age, smoking history, and collagen and elastin composition of the
      hyoepiglottic ligament. RESULTS: The average age of the specimens was 68.4 +/-
      15.1 years (range 30-90 years). Increasing age was associated with a lower
      percentage of collagen and elastin fibers. When accounting for tobacco use, each
      1-year increase in age was associated with a 0.53% decrease in Masson's trichrome
      staining (P = 0.004), a 0.35% decrease in Picrosirius red staining (P = 0.023),
      and a 0.33% decrease in Verhoeff-Van Gieson staining (P = 0.008). CONCLUSION:
      Increasing age is associated with decreases in the collagen and elastin content
      of the hyoepiglottic ligament. LEVEL OF EVIDENCE: NA. Laryngoscope, 128:1245
      1248, 2018.

PMID- 29330865
TI  - A case of radiation-induced osteosarcoma of the skull presenting as a cutaneous
      epidermotropic tumor with a short latent period.
AB  - Radiation-induced sarcoma (RIS) is an unusual but well documented tumor. The
      frequency of RIS of the head and neck region has been reported as 0.143%. In the
      literature the median interval between irradiation and development of sarcoma is
      11 years. Cases of RIS with a short latent period, that is, less than 4 years are
      rare. We report a case of a 34-year-old female who developed an osteosarcoma of
      the scalp, over a previous craniotomy scar, 3 years after excision of a frontal
      anaplastic oligodendroglioma which had been followed by a course of 6 weeks
      radiotherapy (58 Gy) and 6 cycles of temozolomide. The histological features were
      those of a high-grade osteosarcoma with epidermotropism of tumor cells. Lymph
      nodes were partially replaced by high-grade metastatic osteosarcoma, with extra
      nodal lymphatic tumor thrombi. To our knowledge the only other case report of
      post-radiation osteosarcoma with a short latency period was a case of
      osteosarcoma in the craniofacial bone 3 years after radiotherapy for maxillary
      squamous cell carcinoma. The histological finding of prominent replacement of the
      epidermis by osteosarcoma has not been reported before.

PMID- 29330866
TI  - Enteric viruses' dissemination in a private reserve of natural heritage.
AB  - : This study aimed to assess anthropogenic impact of surrounding population in
      the Private Reserve of Natural Heritage at Pantanal, the world's largest
      freshwater wetland ecosystem located in the centre of South America. Viral
      aetiological agents of acute gastroenteritis as rotavirus A (RVA), noroviruses,
      human adenoviruses, klassevirus and of hepatitis, as hepatitis A virus, were
      investigated in different aquatic matrices. Annual collection campaigns were
      carried out from 2009 to 2012, alternating dry and rainy seasons. Viral particles
      present in the samples were concentrated by the adsorption-elution method, with
      negatively charged membranes, and detected by qualitative and quantitative PCR.
      From a total of 43 samples at least one virus was detected in 65% (28) of them.
      Viruses were detected in all matrices with concentrations ranging from 2 * 102 to
      8.3 * 104 genome copies per litre. A significant higher RVA frequency was
      observed in the dry season. Our data revealing dissemination of human enteric
      viruses in water matrices both inside and outside the reserve could be useful to
      trace faecal contamination in the environment and to minimize the risk of
      infection by exposure of susceptible individuals. SIGNIFICANCE AND IMPACT OF THE
      STUDY: This study is part of a collaborative project designed to investigate the
      environmental and health conditions of the Private Reserve of Natural Heritage at
      Pantanal, the largest seasonally flooded wetland in the world. The project aimed
      to promote health and quality of human and wildlife extending technical
      scientific knowledge about pathogens present in the region. By assessing the
      occurrence of human enteric viruses in different water matrices we demonstrated
      the anthropogenic impact of surrounding population and pointed out the potential
      risk of infection by exposure of susceptible individuals.

PMID- 29330868
TI  - Insulin resistance and the increased risk for smell dysfunction in US adults.
AB  - OBJECTIVE: Over 24% of older American adults (approximately 14 million) are
      estimated to have reduced olfactory sensitivity. Previous studies have provided
      evidence that patients with diabetes mellitus (DM) or its complications are at
      increased risk of olfactory dysfunction. We therefore investigated whether smell
      dysfunction was associated with DM-related biomarkers, including fasting blood
      glucose, glycohemoglobin, serum insulin, and homeostasis model assessment of
      insulin sensitivity (HOMA-IR), in older US adults. METHODS: Data from 9,678 older
      adults who had participated in the 2013 to 2014 National Health and Nutrition
      Examination Survey were available for this study. We used the eight-item, self
      administered scratch-and-sniff smell test (Sensonics, Inc., Haddon Heights, NJ)
      for assessing smell. Smell dysfunction was defined as the condition with an odor
      identification score of <= 5. RESULTS: Of the 978 participants, 20% of older
      adults (n = 193) were defined as having smell dysfunction. After adjustment for
      potential confounding variables, participants in the highest HOMA-IR quintile had
      approximately two-fold increased odds (odds ratio = 2.25; 95% confidence
      interval: 1.25-4.05) of smell dysfunction compared with those in the lowest HOMA
      IR quintile. In contrast, the odds of smell dysfunction were not associated with
      the quintiles for fasting blood glucose, glycohemoglobin (HbA1c), or serum
      insulin levels. CONCLUSION: We found a significant association between smell
      dysfunction and severe insulin resistance in older US adults. Our data suggests
      that insulin resistance may be mechanistically linked to loss of smell function.
      LEVEL OF EVIDENCE: 4. Laryngoscope, 128:1992-1996, 2018.

PMID- 29330867
TI  - Preferential cholinergic excitation of corticopontine neurons.
AB  - KEY POINTS: Phasic activation of M1 muscarinic receptors generates transient
      inhibition followed by longer lasting excitation in neocortical pyramidal
      neurons. Corticopontine neurons in the mouse prefrontal cortex exhibit weaker
      cholinergic inhibition, but more robust and longer lasting excitation, than
      neighbouring callosal projection neurons. Optogenetic release of endogenous ACh
      in response to single flashes of light (5 ms) preferentially enhances the
      excitability of corticopontine neurons for many tens of seconds. Cholinergic
      excitation of corticopontine neurons involves at least three ionic mechanisms:
      suppression of KV 7 currents, activation of the calcium-dependent non-specific
      cation conductance underlying afterdepolarizations, and activation of what
      appears to be a calcium-sensitive but calcium-permeable non-specific cation
      conductance. Preferential cholinergic excitation of prefrontal corticopontine
      neurons may facilitate top-down attentional processes and behaviours. ABSTRACT:
      Pyramidal neurons in layer 5 of the neocortex comprise two broad classes of
      projection neurons: corticofugal neurons, including corticopontine (CPn) neurons,
      and intratelencephalic neurons, including commissural/callosal (COM) neurons.
      These non-overlapping neuron subpopulations represent discrete cortical output
      channels contributing to perception, decision making and behaviour. CPn and COM
      neurons have distinct morphological and physiological characteristics, and
      divergent responses to modulatory transmitters such as serotonin and
      acetylcholine (ACh). To better understand how ACh regulates cortical output, in
      slices of mouse prefrontal cortex (PFC) we compared the responsivity of CPn and
      COM neurons to transient exposure to exogenous or endogenous ACh. In both neuron
      subtypes, exogenous ACh generated qualitatively similar biphasic responses in
      which brief hyperpolarization was followed by longer lasting enhancement of
      excitability. However, cholinergic inhibition was more pronounced in COM neurons,
      while excitatory responses were larger and longer lasting in CPn neurons.
      Similarly, optically triggered release of endogenous ACh from cholinergic
      terminals preferentially and persistently (for ~40 s) enhanced the excitability
      of CPn neurons, but had little impact on COM neurons. Cholinergic excitation of
      CPn neurons involved at least three distinct ionic mechanisms: suppression of KV
      7 channels (the 'M-current'), activation of the calcium-dependent non-specific
      cation conductance underlying afterdepolarizations, and activation of what
      appears to be a calcium-sensitive but calcium-permeable non-specific cation
      conductance. Our findings demonstrate projection-specific selectivity in
      cholinergic signalling in the PFC, and suggest that transient release of ACh
      during behaviour will preferentially promote corticofugal output.

PMID- 29330835
TI  - International guidelines for groin hernia management.
AB  - INTRODUCTION: Worldwide, more than 20 million patients undergo groin hernia
      repair annually. The many different approaches, treatment indications and a
      significant array of techniques for groin hernia repair warrant guidelines to
      standardize care, minimize complications, and improve results. The main goal of
      these guidelines is to improve patient outcomes, specifically to decrease
      recurrence rates and reduce chronic pain, the most frequent problems following
      groin hernia repair. They have been endorsed by all five continental hernia
      societies, the International Endo Hernia Society and the European Association for
      Endoscopic Surgery. METHODS: An expert group of international surgeons (the
      HerniaSurge Group) and one anesthesiologist pain expert was formed. The group
      consisted of members from all continents with specific experience in hernia
      related research. Care was taken to include surgeons who perform different types
      of repair and had preferably performed research on groin hernia surgery. During
      the Group's first meeting, evidence-based medicine (EBM) training occurred and
      166 key questions (KQ) were formulated. EBM rules were followed in complete
      literature searches (including a complete search by The Dutch Cochrane database)
      to January 1, 2015 and to July 1, 2015 for level 1 publications. The articles
      were scored by teams of two or three according to Oxford, SIGN and Grade
      methodologies. During five 2-day meetings, results were discussed with the
      working group members leading to 136 statements and 88 recommendations.
      Recommendations were graded as "strong" (recommendations) or "weak" (suggestions)
      and by consensus in some cases upgraded. In the Results and summary section
      below, the term "should" refers to a recommendation. The AGREE II instrument was
      used to validate the guidelines. An external review was performed by three
      international experts. They recommended the guidelines with high scores. The risk
      factors for inguinal hernia (IH) include: family history, previous contra-lateral
      hernia, male gender, age, abnormal collagen metabolism, prostatectomy, and low
      body mass index. Peri-operative risk factors for recurrence include poor surgical
      techniques, low surgical volumes, surgical inexperience and local anesthesia.
      These should be considered when treating IH patients. IH diagnosis can be
      confirmed by physical examination alone in the vast majority of patients with
      appropriate signs and symptoms. Rarely, ultrasound is necessary. Less commonly
      still, a dynamic MRI or CT scan or herniography may be needed. The EHS
      classification system is suggested to stratify IH patients for tailored
      treatment, research and audit. Symptomatic groin hernias should be treated
      surgically. Asymptomatic or minimally symptomatic male IH patients may be managed
      with "watchful waiting" since their risk of hernia-related emergencies is low.
      The majority of these individuals will eventually require surgery; therefore,
      surgical risks and the watchful waiting strategy should be discussed with
      patients. Surgical treatment should be tailored to the surgeon's expertise,
      patient- and hernia-related characteristics and local/national resources.
      Furthermore, patient health-related, life style and social factors should all
      influence the shared decision-making process leading up to hernia management.
      Mesh repair is recommended as first choice, either by an open procedure or a
      laparo-endoscopic repair technique. One standard repair technique for all groin
      hernias does not exist. It is recommended that surgeons/surgical services provide
      both anterior and posterior approach options. Lichtenstein and laparo-endoscopic
      repair are best evaluated. Many other techniques need further evaluation.
      Provided that resources and expertise are available, laparo-endoscopic techniques
      have faster recovery times, lower chronic pain risk and are cost effective. There
      is discussion concerning laparo-endoscopic management of potential bilateral
      hernias (occult hernia issue). After patient consent, during TAPP, the contra
      lateral side should be inspected. This is not suggested during unilateral TEP
      repair. After appropriate discussions with patients concerning results tissue
      repair (first choice is the Shouldice technique) can be offered. Day surgery is
      recommended for the majority of groin hernia repair provided aftercare is
      organized. Surgeons should be aware of the intrinsic characteristics of the
      meshes they use. Use of so-called low-weight mesh may have slight short-term
      benefits like reduced postoperative pain and shorter convalescence, but are not
      associated with better longer-term outcomes like recurrence and chronic pain.
      Mesh selection on weight alone is not recommended. The incidence of erosion seems
      higher with plug versus flat mesh. It is suggested not to use plug repair
      techniques. The use of other implants to replace the standard flat mesh in the
      Lichtenstein technique is currently not recommended. In almost all cases, mesh
      fixation in TEP is unnecessary. In both TEP and TAPP it is recommended to fix
      mesh in M3 hernias (large medial) to reduce recurrence risk. Antibiotic
      prophylaxis in average-risk patients in low-risk environments is not recommended
      in open surgery. In laparo-endoscopic repair it is never recommended. Local
      anesthesia in open repair has many advantages, and its use is recommended
      provided the surgeon is experienced in this technique. General anesthesia is
      suggested over regional in patients aged 65 and older as it might be associated
      with fewer complications like myocardial infarction, pneumonia and
      thromboembolism. Perioperative field blocks and/or subfascial/subcutaneous
      infiltrations are recommended in all cases of open repair. Patients are
      recommended to resume normal activities without restrictions as soon as they feel
      comfortable. Provided expertise is available, it is suggested that women with
      groin hernias undergo laparo-endoscopic repair in order to decrease the risk of
      chronic pain and avoid missing a femoral hernia. Watchful waiting is suggested in
      pregnant women as groin swelling most often consists of self-limited round
      ligament varicosities. Timely mesh repair by a laparo-endoscopic approach is
      suggested for femoral hernias provided expertise is available. All complications
      of groin hernia management are discussed in an extensive chapter on the topic.
      Overall, the incidence of clinically significant chronic pain is in the 10-12%
      range, decreasing over time. Debilitating chronic pain affecting normal daily
      activities or work ranges from 0.5 to 6%. Chronic postoperative inguinal pain
      (CPIP) is defined as bothersome moderate pain impacting daily activities lasting
      at least 3 months postoperatively and decreasing over time. CPIP risk factors
      include: young age, female gender, high preoperative pain, early high
      postoperative pain, recurrent hernia and open repair. For CPIP the focus should
      be on nerve recognition in open surgery and, in selected cases, prophylactic
      pragmatic nerve resection (planned resection is not suggested). It is suggested
      that CPIP management be performed by multi-disciplinary teams. It is also
      suggested that CPIP be managed by a combination of pharmacological and
      interventional measures and, if this is unsuccessful, followed by, in selected
      cases (triple) neurectomy and (in selected cases) mesh removal. For recurrent
      hernia after anterior repair, posterior repair is recommended. If recurrence
      occurs after a posterior repair, an anterior repair is recommended. After a
      failed anterior and posterior approach, management by a specialist hernia surgeon
      is recommended. Risk factors for hernia incarceration/strangulation include:
      female gender, femoral hernia and a history of hospitalization related to groin
      hernia. It is suggested that treatment of emergencies be tailored according to
      patient- and hernia-related factors, local expertise and resources. Learning
      curves vary between different techniques. Probably about 100 supervised laparo
      endoscopic repairs are needed to achieve the same results as open mesh surgery
      like Lichtenstein. It is suggested that case load per surgeon is more important
      than center volume. It is recommended that minimum requirements be developed to
      certify individuals as expert hernia surgeon. The same is true for the
      designation "Hernia Center". From a cost-effectiveness perspective, day-case
      laparoscopic IH repair with minimal use of disposables is recommended. The
      development and implementation of national groin hernia registries in every
      country (or region, in the case of small country populations) is suggested. They
      should include patient follow-up data and account for local healthcare
      structures. A dissemination and implementation plan of the guidelines will be
      developed by global (HerniaSurge), regional (international societies) and local
      (national chapters) initiatives through internet websites, social media and
      smartphone apps. An overarching plan to improve access to safe IH surgery in low
      resource settings (LRSs) is needed. It is suggested that this plan contains
      simple guidelines and a sustainability strategy, independent of international
      aid. It is suggested that in LRSs the focus be on performing high-volume
      Lichtenstein repair under local anesthesia using low-cost mesh. Three chapters
      discuss future research, guidelines for general practitioners and guidelines for
      patients. CONCLUSIONS: The HerniaSurge Group has developed these extensive and
      inclusive guidelines for the management of adult groin hernia patients. It is
      hoped that they will lead to better outcomes for groin hernia patients wherever
      they live. More knowledge, better training, national audit and specialization in
      groin hernia management will standardize care for these patients, lead to more
      effective and efficient healthcare and provide direction for future research.

PMID- 29330869
TI  - Three-year analysis of zirconia implants used for single-tooth replacement and
      three-unit fixed dental prostheses: A prospective multicenter study.
AB  - AIM: The aim of the present investigation was to evaluate clinically and
      radiographically the outcome of zirconia oral implants after 3 years in function.
      MATERIALS AND METHODS: In 60 patients in need of either a single-tooth
      replacement or a three-unit fixed dental prosthesis (FDP), a total of 71 one
      piece zirconia implants were placed and immediately restored with temporary fixed
      prostheses. After a period of at least 2 months in the mandible and at least 4
      months in the maxilla, zirconia-based reconstructions were cemented. The implants
      were clinically and radiologically examined at implant insertion, prosthetic
      delivery, at 6 months and then yearly up to 3 years. A linear mixed model was
      used to analyze statistically the influence of prognostic factors on changes in
      the marginal bone level. RESULTS: Seventy-one implants (48 in the mandible, 23 in
      the maxilla) inserted in 60 patients were restored with 49 crowns and 11 FDP. One
      patient lost his implant after 5 weeks. Five patients with one implant each could
      not be evaluated after 3 years. Based on 55 patients with a total of 66 implants,
      the mean survival rate was 98.5% after 3 years in function. A statistically
      significant mean marginal bone loss (0.70 mm +/- 0.72 mm) has been detected from
      implant insertion to the 3-year follow-up. The largest marginal bone loss
      occurred between implantation and prosthetic delivery (0.67 mm +/- 0.56 mm).
      After delivery, no statistically significant bone level change was observed (0.02
      mm +/- 0.59 mm). None of the investigated prognostic factors had a significant
      influence on changes in the marginal bone level. CONCLUSIONS: After 3 years in
      function, the investigated one-piece zirconia implant showed a high survival rate
      and a low marginal bone loss. The implant system was successful for single-tooth
      replacement and three-unit FDPs. Further investigations with long-term data are
      needed to confirm these findings.

PMID- 29330870
TI  - Cell therapy for spinal cord injury with olfactory ensheathing glia cells (OECs).
AB  - The prospects of achieving regeneration in the central nervous system (CNS) have
      changed, as most recent findings indicate that several species, including humans,
      can produce neurons in adulthood. Studies targeting this property may be
      considered as potential therapeutic strategies to respond to injury or the
      effects of demyelinating diseases in the CNS. While CNS trauma may interrupt the
      axonal tracts that connect neurons with their targets, some neurons remain alive,
      as seen in optic nerve and spinal cord (SC) injuries (SCIs). The devastating
      consequences of SCIs are due to the immediate and significant disruption of the
      ascending and descending spinal pathways, which result in varying degrees of
      motor and sensory impairment. Recent therapeutic studies for SCI have focused on
      cell transplantation in animal models, using cells capable of inducing axon
      regeneration like Schwann cells (SchCs), astrocytes, genetically modified
      fibroblasts and olfactory ensheathing glia cells (OECs). Nevertheless, and
      despite the improvements in such cell-based therapeutic strategies, there is
      still little information regarding the mechanisms underlying the success of
      transplantation and regarding any secondary effects. Therefore, further studies
      are needed to clarify these issues. In this review, we highlight the properties
      of OECs that make them suitable to achieve neuroplasticity/neuroregeneration in
      SCI. OECs can interact with the glial scar, stimulate angiogenesis, axon
      outgrowth and remyelination, improving functional outcomes following lesion.
      Furthermore, we present evidence of the utility of cell therapy with OECs to
      treat SCI, both from animal models and clinical studies performed on SCI
      patients, providing promising results for future treatments.

PMID- 29330872
TI  - Repair of high-grade posterior glottic stenosis: A novel criocarytenoid joint
      release technique.

PMID- 29330871
TI  - Multi-site N-Glycan mapping study 2: UHPLC.
AB  - In the first part of this publication, the results from an international study
      evaluating the precision (i.e., repeatability and reproducibility) of N
      glycosylation analysis using capillary electrophoresis of APTS-labeled N-glycans
      were presented. The corresponding results from ultra-high performance liquid
      chromatography (UHPLC) with fluorescence detection are presented here from 12
      participating sites. All participants used the same lot of samples, reagents, and
      columns to perform the assays. Elution time, peak area and peak area percent
      values were determined for all peaks >=0.1% peak area, and statistical analysis
      was performed following ISO 5725-2 guideline principles. The results demonstrated
      adequate reproducibility, within any given site as well across all sites,
      indicating that standard UHPLC-based N-glycan analysis platforms are appropriate
      for general use.

PMID- 29330874
TI  - Safety of high-current stimulation for intermittent intraoperative neural
      monitoring in thyroid surgery: A porcine model.
AB  - OBJECTIVES: During monitored thyroidectomy, displacement of the recurrent
      laryngeal nerve (RLN) or vagus nerve (VN) in some complicated cases can increase
      the risk of injury. Although increasing the stimulus current can facilitate nerve
      mapping and localization, the safety of a high-current stimulus remains unknown.
      Therefore, this study evaluated the safety of a high-current stimulus in a
      porcine model. METHODS: Short-duration (1 minute), high-current (3, 5, 10, 15,
      20, 25, and 30 mA at 4Hz) stimulus pulses were repeatedly applied to the RLN or
      VN in six anesthetized piglets. The safety of the high-current stimulus pulses
      was assessed in terms of hemodynamic stability during VN stimulation and in terms
      of nerve function integrity after VN and RLN stimulation. RESULTS: During VN
      stimulation with a high-current stimulus pulse, sinus rhythms in all six piglets
      showed stable heart rates, and mean arterial pressure was unaffected. High
      current stimulation of the VN and the RLN did not affect electromyography
      amplitude or latency. CONCLUSION: This porcine study showed that applying a short
      duration, high-current stimulus pulse to the VN or RLN during monitored
      thyroidectomy has no harmful effects. In clinical practice, a short duration of
      high-current stimulus can be applied to facilitate neural mapping, especially in
      patients with disoriented nerve positions. LEVEL OF EVIDENCE: NA. Laryngoscope,
      128:2206-2212, 2018.

PMID- 29330875
TI  - Performance of the Early Access AmpliSeqTM Mitochondrial Panel with degraded DNA
      samples using the Ion TorrentTM platform.
AB  - The Early Access AmpliSeqTM Mitochondrial Panel amplifies whole mitochondrial
      genomes for phylogenetic and kinship identifications, using Ion TorrentTM
      technology. There is currently limited information on its performance with
      degraded DNA, a common occurrence in forensic samples. This study evaluated the
      performance of the Panel with DNA samples degraded in vitro, to mimic conditions
      commonly found in forensic investigations. Purified DNA from five individuals was
      heat-treated at five time points each (125 degrees C for 0, 30, 60, 120, and 240
      min; total n = 25). The quality of DNA was assessed via a real-time DNA assay of
      genomic DNA and prepared for massively parallel sequencing on the Ion TorrentTM
      platform. Mitochondrial sequences were obtained for all samples and had an
      amplicon coverage averaging between 66X to 2803X. Most amplicons (157/162)
      displayed high coverages (452 +/- 333X), while reads with less than 100X coverage
      were recorded in five amplicons only (90 +/- 5X). Amplicon coverage was decreased
      with prolonged heating. At 72% strand balance, reads were well balanced between
      forward and reverse strands. Using a coverage threshold of ten reads per SNP,
      complete sequences were recovered in all samples and resolved kinship and,
      haplogroup relations. Additionally, the HV1 and HV2 regions of the reference and
      240-min heat-treated samples (n = 10) were Sanger-sequenced for concordance.
      Overall, this study demonstrates the efficacy of a novel forensic Panel that
      recovers high quality mitochondrial sequences from degraded DNA samples.

PMID- 29330873
TI  - Coupling colloidal forces with yield stress of charged inorganic particle
      suspension: A review.
AB  - This paper aims to summarize the series of investigations on coupling suspension
      yield stress and DLVO (Derjaguin-Landau-Verwey-Overbeek) forces, i.e. van der
      Waals and electrical double layer forces. This summary provides a better
      understanding of the basic phenomena associated, historical development and
      current status of this useful coupling, and also discusses the applicability and
      limitations/variations of such coupling applied to different types of
      concentrated aqueous particle suspensions. Aqueous suspensions discussed are
      composed of charged inorganic fine particles, including metal oxide colloidal
      particles, mineral fine particles, and clays. The research gaps are identified
      and specific future perspectives are discussed to further enhance the use of this
      unique and useful coupling, and to aim for the transition from the modelling of
      similar particle suspension systems to its dissimilar/mix particle suspension
      systems that fit more with the current and future industry needs in particle
      processing.

PMID- 29330876
TI  - A rare case of topical methazolamide ophthalmic solution causing death due to
      toxic epidermal necrolysis.

PMID- 29330877
TI  - Characterization of biologic response modifiers in the supernatant of
      conventional, refrigerated, and cryopreserved platelets.
AB  - BACKGROUND: Alternatives to room temperature storage of platelets (PLTs) are of
      interest to support blood banking logistics. The aim of this study was to compare
      the presence of biologic response modifiers (BRMs) in PLT concentrates stored
      under conventional room temperature conditions with refrigerated or cryopreserved
      PLTs. STUDY DESIGN AND METHODS: A three-arm pool-and-split study was carried out
      using buffy coat-derived PLTs stored in 30% plasma/70% SSP+. The three matched
      treatment arms were as follows: room temperature (20-24 degrees C), cold (2-6
      degrees C), and cryopreserved (-80 degrees C with DMSO). Liquid-stored PLTs were
      tested over a 21-day period, while cryopreserved PLTs were tested immediately
      after thawing and reconstitution in 30% plasma/70% SSP+ and after storage at room
      temperature. RESULTS: Coagulation factor activity was comparable between room
      temperature and cold PLTs, with the exception of protein S, while cryopreserved
      PLTs had reduced Factor (F)V and FVIII activity. Cold-stored PLTs retained alpha
      granule proteins better than room temperature or cryopreserved PLTs.
      Cryopreservation resulted in 10-fold higher microparticle generation than cold
      stored PLTs, but both groups contained significantly more microparticles than
      those stored at room temperature. The supernatant from both cold and
      cryopreserved PLTs initiated faster clot formation and thrombin generation than
      room temperature PLTs. CONCLUSION: Cold storage and cryopreservation alter the
      composition of the soluble fraction of stored PLTs. These differences in
      coagulation proteins, cytokines, and microparticles likely influence both the
      hemostatic capacity of the components and the auxiliary functions.

PMID- 29330878
TI  - Identification of tentative marker in Corvina and Primitivo wines with CMC-se.
AB  - This paper introduces CMC-se-a program for computer-assisted structure
      elucidation. In the experimental part, the combination of modern analytical
      methods (LC-SPE-NMR/MS) and structure elucidation software is used for the
      identification of tentative markers in red wines.

PMID- 29330879
TI  - Biotechnological conversion of spent coffee grounds into lactic acid.
AB  - : This work investigates the potential bioconversion of spent coffee grounds
      (SCG) into lactic acid (LA). SCG were hydrolysed by a combination of dilute acid
      treatment and subsequent application of cellulase. The SCG hydrolysate contained
      a considerable amount of reducing sugars (9.02 +/- 0.03 g l-1 , glucose; 26.49 +/
      0.10 g l-1 galactose and 2.81 +/- 0.07 g l-1 arabinose) and it was used as a
      substrate for culturing several lactic acid bacteria (LAB) and LA-producing
      Bacillus coagulans. Among the screened micro-organisms, Lactobacillus rhamnosus
      CCM 1825 was identified as the most promising producer of LA on a SCG
      hydrolysate. Despite the inhibitory effect exerted by furfural and phenolic
      compounds in the medium, reasonably high LA concentrations (25.69 +/- 1.45 g l-1
      ) and yields (98%) were gained. Therefore, it could be demonstrated that SCG is a
      promising raw material for the production of LA and could serve as a feedstock
      for the sustainable large-scale production of LA. SIGNIFICANCE AND IMPACT OF THE
      STUDY: Spent coffee grounds (SCG) represent solid waste generated in millions of
      tonnes by coffee-processing industries. Their disposal represents a serious
      environmental problem; however, SCG could be valorized within a biorefinery
      concept yielding various valuable products. Herein, we suggest that SCG can be
      used as a complex carbon source for the lactic acid production.

PMID- 29330880
TI  - Concise Review: Optimized Strategies for Stem Cell-Based Therapy in Myocardial
      Repair: Clinical Translatability and Potential Limitation.
AB  - Ischemic heart diseases (IHDs) remain major public health problems with high
      rates of morbidity and mortality worldwide. Despite significant advances, current
      therapeutic approaches are unable to rescue the extensive and irreversible loss
      of cardiomyocytes caused by severe ischemia. Over the past 16 years, stem cell
      based therapy has been recognized as an innovative strategy for cardiac
      repair/regeneration and functional recovery after IHDs. Although substantial
      preclinical animal studies using a variety of stem/progenitor cells have shown
      promising results, there is a tremendous degree of skepticism in the clinical
      community as many stem cell trials do not confer any beneficial effects. How to
      accelerate stem cell-based therapy toward successful clinical application
      attracts considerate attention. However, many important issues need to be fully
      addressed. In this Review, we have described and compared the effects of
      different types of stem cells with their dose, delivery routes, and timing that
      have been routinely tested in recent preclinical and clinical findings. We have
      also discussed the potential mechanisms of action of stem cells, and explored the
      role and underlying regulatory components of stem cell-derived
      secretomes/exosomes in myocardial repair. Furthermore, we have critically
      reviewed the different strategies for optimizing both donor stem cells and the
      target cardiac microenvironments to enhance the engraftment and efficacy of stem
      cells, highlighting their clinical translatability and potential limitation. Stem
      Cells 2018;36:482-500.

PMID- 29330882
TI  - Rate of Cough During Treatment With Angiotensin-Converting Enzyme Inhibitors: A
      Meta-Analysis of Randomized Placebo-Controlled Trials.
AB  - Use of protective angiotensin-converting enzyme inhibitors (ACE-I) in patients
      with cardiovascular disease (CVD) is sometimes limited by incident coughing. In
      clinical trials, cough occurred also on placebo. We performed a meta-analysis
      including randomized, placebo-controlled trials reporting cough on ACE-I in
      patients with CVD. We evaluated the attributable fraction of cough on ACE-I
      accounting rate on placebo: placebo-adjusted ACE-I (%) = (ACE-I (%) - Placebo
      (%)) / ACE-I (%). In total, 65,054 patients from 22 included studies were
      analyzed. Placebo-adjusted ACE-I cough was 37% of 13.5% reported cases on ACE-I,
      while 8.5% reported cases on placebo were equivalent to 63% of cases on ACE-I,
      indicating potential other factors for cough than ACE-I in a substantial number
      of cough cases on ACE-I. Placebo-adjusted ACE-I cough had the highest rates of
      arterial hypertension (85%) and the lowest of heart failure (29%). Therefore,
      other causes of cough, particularly in heart failure, should be excluded before
      ACE-I withdrawal.

PMID- 29330881
TI  - Cocaine and HIV-1 Tat disrupt cholesterol homeostasis in astrocytes: Implications
      for HIV-associated neurocognitive disorders in cocaine user patients.
AB  - Cholesterol synthesis and clearance by astrocytes are tightly regulated to
      maintain constant levels within the brain. In this context, liver X receptors
      (LXRs) are the master regulators of cholesterol homeostasis in the central
      nervous system (CNS). Increasing levels of cholesterol in astrocytes trigger LXR
      activation leading to the transcription of target genes involved in cholesterol
      trafficking and efflux, including apolipoprotein E, cytochrome P450 enzymes,
      sterol regulatory binding protein, and several ATP-binding cassette transporter
      proteins. The disturbance of LXR signaling in the brain can lead to significant
      dysfunctions in cholesterol homeostasis, and disruptions in this pathway have
      been implicated in numerous neurological diseases including Alzheimer's disease
      and Huntington's disease. HIV infection of the CNS in combination with cocaine
      use is associated with astrocyte and neuronal energy deficit and damage. We
      propose that dysregulation in CNS cholesterol metabolism may be involved in the
      progression of HIV-associated neurocognitive disorders (HAND) and in cocaine
      mediated neurocognitive impairments. We hypothesize that exposure of astrocytes
      to cocaine and the HIV protein Tat will disrupt LXR signaling. Alterations in
      these pathways will in turn, affect cholesterol bioavailability for neurons. Our
      data show that exposure of astrocytes to cocaine and HIV-Tat significantly
      decreases LXRbeta levels, downstream signaling and bioavailability of
      cholesterol. Taken together, these data uncover novel alterations in a
      bioenergetic pathway in astrocytes exposed to cocaine and the HIV protein Tat.
      Results from these studies point to a new pathway in the CNS that may contribute
      to HAND in HIV+ cocaine user individuals.

PMID- 29330884
TI  - Synapsin III is a key component of alpha-synuclein fibrils in Lewy bodies of PD
      brains.
AB  - Lewy bodies (LB) and Lewy neurites (LN), which are primarily composed of alpha
      synuclein (alpha-syn), are neuropathological hallmarks of Parkinson's disease
      (PD) and dementia with Lewy bodies (DLB). We recently found that the neuronal
      phosphoprotein synapsin III (syn III) controls dopamine release via cooperation
      with alpha-syn and modulates alpha-syn aggregation. Here, we observed that LB and
      LN, in the substantia nigra of PD patients and hippocampus of one subject with
      DLB, displayed a marked immunopositivity for syn III. The in situ proximity
      ligation assay revealed the accumulation of numerous proteinase K-resistant
      neuropathological inclusions that contained both alpha-syn and syn III in tight
      association in the brain of affected subjects. Most strikingly, syn III was
      identified as a component of alpha-syn-positive fibrils in LB-enriched protein
      extracts from PD brains. Finally, a positive correlation between syn III and
      alpha-syn levels was detected in the caudate putamen of PD subjects.
      Collectively, these findings indicate that syn III is a crucial alpha-syn
      interactant and a key component of LB fibrils in the brain of patients affected
      by PD.

PMID- 29330883
TI  - Genotype-phenotype correlations in individuals with pathogenic RERE variants.
AB  - Heterozygous variants in the arginine-glutamic acid dipeptide repeats gene (RERE)
      have been shown to cause neurodevelopmental disorder with or without anomalies of
      the brain, eye, or heart (NEDBEH). Here, we report nine individuals with NEDBEH
      who carry partial deletions or deleterious sequence variants in RERE. These
      variants were found to be de novo in all cases in which parental samples were
      available. An analysis of data from individuals with NEDBEH suggests that point
      mutations affecting the Atrophin-1 domain of RERE are associated with an
      increased risk of structural eye defects, congenital heart defects, renal
      anomalies, and sensorineural hearing loss when compared with loss-of-function
      variants that are likely to lead to haploinsufficiency. A high percentage of RERE
      pathogenic variants affect a histidine-rich region in the Atrophin-1 domain. We
      have also identified a recurrent two-amino-acid duplication in this region that
      is associated with the development of a CHARGE syndrome-like phenotype. We
      conclude that mutations affecting RERE result in a spectrum of clinical
      phenotypes. Genotype-phenotype correlations exist and can be used to guide
      medical decision making. Consideration should also be given to screening for RERE
      variants in individuals who fulfill diagnostic criteria for CHARGE syndrome but
      do not carry pathogenic variants in CHD7.

PMID- 29330885
TI  - Prolonged duration of persistent cell-free fetal DNA from vanishing twin.

PMID- 29330886
TI  - Surgery and magnetic resonance imaging increase the risk of hypothermia in
      infants.
AB  - AIM: Maintaining normothermia is a tenet of neonatal care. However, neonatal
      thermal care guidelines applicable to intra-hospital transport beyond the
      neonatal intensive care unit (NICU) and during surgery or magnetic resonance
      imaging (MRI) are lacking. The aim of this study is to determine the proportion
      of infants normothermic (36.5-37.5 degrees C) on return to NICU after management
      during surgery and MRI, and during standard clinical care in both environments.
      METHODS: Sixty-two newborns requiring either surgery in the operating theatre
      (OT) (n = 41) or an MRI scan (n = 21) at the Royal Children's Hospital
      (Melbourne) NICU were prospectively studied. Core temperature, along with
      cardiorespiratory parameters, was continuously measured from 15 min prior to
      leaving the NICU until 60 min after returning. Passive and active warming (intra
      operatively) was at clinician discretion. RESULTS: The study reported 90% of
      infants were normothermic before leaving NICU: 86% (MRI) and 93% (OT). Only 52%
      of infants were normothermic on return to NICU (relative risk (RR) 1.75; 95%
      confidence interval (CI) 1.39-2.31; number needed to harm (NNH) 2.6). Between
      departure from the NICU and commencement of surgery, core temperature decreased
      by mean 0.81 degrees C (95% CI 0.30-1.33; P = 0.0001, analysis of variance), with
      only 24% of infants normothermic when surgery began (P < 0.0001; RR 3.80 (95% CI
      2.33-6.74); NNH 1.5). After an MRI, infants were a mean 0.41 degrees C (95% CI
      0.16-0.67) colder than immediately before entering the scanner (P = 0.001,
      analysis of variance), with only 43% being normothermic (P = 0.003; RR 2.11 (95%
      CI 1.35-3.74); NNH 2.1). CONCLUSION: Unintentional hypothermia is a common
      occurrence during surgery in the OT and MRI in neonates, indicating that evidence
      based warming strategies to prevent hypothermia should be developed.

PMID- 29330888
TI  - McRoberts' maneuver increases fetal head angle of progression in second stage of
      labor.

PMID- 29330887
TI  - Loss of VAMP5 in mice results in duplication of the ureter and insufficient
      expansion of the lung.
AB  - BACKGROUND: Vesicle-associated membrane protein 5 (VAMP5) is a member of the
      SNARE protein family, which regulates the docking and fusion of membrane vesicles
      within cells. Previously, we reported ubiquitous expression of VAMP5 proteins in
      various organs except the brain and small intestine. However, the precise roles
      of VAMP5 in each organ remain unclear. To explore the roles of VAMP5 in vivo, we
      generated VAMP5 knockout (KO) mice. RESULTS: VAMP5 KO mice showed low birth rate
      and low body weight. KO embryos grew normally in the uterus, and tended to die
      around birth. Anatomical analysis revealed that viable KO mice often exhibited
      duplication of the ureter, and dead KO mice showed insufficient expansion of the
      lung. VAMP5 was localized in the epithelial cells of the ureter and terminal
      bronchiole. CONCLUSIONS: VAMP5 KO mice showed a low birth rate and abnormalities
      of the urinary and respiratory systems. VAMP5 KO mice died around birth, possibly
      due to defects in vesicoureteral flow and breathing. The results presented could
      provide a basis for future studies to understand the roles of VAMP5 protein.
      Developmental Dynamics 247:754-762, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 29330889
TI  - Exercise desaturation and oxygen therapy in ILD and COPD: Similarities,
      differences and therapeutic relevance.

PMID- 29330890
TI  - Audit of referrals for concern regarding labial appearance at the Royal
      Children's Hospital: 2000-2012.
AB  - AIM: To audit the clinical features and outcomes for all patients referred to our
      centre with concerns regarding labial appearance. METHODS: Young females referred
      to a paediatric/adolescent gynaecology tertiary centre between 2000 and 2012 with
      concerns regarding their labial appearance were retrospectively identified.
      Adolescents presenting with anomalies were excluded. Retrospective chart review
      was undertaken to identify reasons for referral, patient characteristics, outcome
      of referral and concurrent health problems. RESULTS: In total, 46 females
      presenting with concerns about labial appearance were identified. Five were
      excluded. Median age of the study population was 14.5 years (range 5-21 years).
      Only four (9.8%) underwent surgery after a minimum of five consultations each,
      with mental health review in three of four cases prior to surgery. None of the 41
      patients had documented abnormal labia; however, 6 patients had asymmetry, and 3
      had a labial width of >5 cm. Of mothers, 24% (n = 10) raised the initial concern
      regarding labial appearance to a physician, of whom, 50% of patients had a
      comorbid condition. In total, 70.7% initially reported interference with daily
      activities, and 87.8% were reassured following discussion. CONCLUSIONS: With
      appropriate education and counselling, the majority of girls with concerns
      regarding labial appearance can be managed without surgery. Overall, our data
      support current international policy that female cosmetic genital surgery not be
      performed in mature minors unless there are specific indications. More research
      about characteristics of patients referred with labial concerns, definition of
      labial size and long-term satisfaction of conservative versus surgical methods is
      necessary to determine the best approach.

PMID- 29330891
TI  - Why do African Americans have a higher risk for cerebral disease?

PMID- 29330892
TI  - Ophthalmic artery Doppler for prediction of pre-eclampsia: systematic review and
      meta-analysis.
AB  - OBJECTIVE: To determine the accuracy of ophthalmic artery Doppler in pregnancy
      for the prediction of pre-eclampsia (PE). METHODS: MEDLINE, EMBASE, CINAHL and
      The Cochrane Library were searched for relevant citations without language
      restrictions. Two reviewers independently selected studies that evaluated the
      accuracy of ophthalmic artery Doppler to predict the development of PE and
      extracted data to construct 2 * 2 tables. Individual patient data were obtained
      from the authors if available. A bivariate random-effects model was used for the
      quantitative synthesis of data. Logistic regression analysis was employed to
      generate receiver-operating characteristics (ROC) curves and obtain optimal cut
      offs for each investigated parameter, and a bivariate analysis was employed using
      predetermined cut-offs to obtain sensitivity and specificity values and generate
      summary ROC curves. RESULTS: A total of 87 citations matched the search criteria
      of which three studies, involving 1119 pregnancies, were included in the
      analysis. All included studies had clear description of the index and reference
      tests, avoidance of verification bias and adequate follow-up. Individual patient
      data were obtained for all three included studies. First diastolic peak velocity
      of ophthalmic artery Doppler at a cut-off of 23.3 cm/s showed modest sensitivity
      (61.0%; 95% CI, 44.2-76.1%) and specificity (73.2%; 95% CI, 66.9-78.7%) for the
      prediction of early-onset PE (area under the ROC curve (AUC), 0.68; 95% CI, 0.61
      0.76). The first diastolic peak velocity had a much lower sensitivity (39.0%; 95%
      CI, 20.6-61.0%), a similar specificity (73.2%; 95% CI, 66.9-78.7%) and a lower
      AUC (0.58; CI, 0.52-0.65) for the prediction of late-onset PE. The pulsatility
      index of the ophthalmic artery did not show a clinically useful sensitivity or
      specificity at any cut-off for early- or late-onset PE. Peak ratio above 0.65
      showed a similar diagnostic accuracy to that of the first diastolic peak velocity
      with an AUC of 0.67 (95% CI, 0.58-0.77) for early-onset PE and 0.57 (95% CI, 0.51
      0.63) for late-onset disease. CONCLUSIONS: Ophthalmic artery Doppler is a simple,
      accurate and objective technique with a standalone predictive value for the
      development of early-onset PE equivalent to that of uterine artery Doppler
      evaluation. The relationship between ophthalmic Doppler indices and PE cannot be
      a consequence of trophoblast invasion and may be related to maternal hemodynamic
      adaptation to pregnancy. The findings of this review justify efforts to elucidate
      the effectiveness and underlying mechanism whereby two seemingly unrelated
      maternal vessels can be used for the prediction of a disease considered a
      'placental disorder'. Copyright (c) 2018 ISUOG. Published by John Wiley & Sons
      Ltd.

PMID- 29330893
TI  - Mitogenomic differences between the normal and tumor cells of colorectal cancer
      patients.
AB  - So far, a reliable spectrum of mitochondrial DNA mutations in colorectal cancer
      cells is still unknown, and neither is their significance in carcinogenesis.
      Indeed, it remains debatable whether mtDNA mutations are "drivers" or
      "passengers" of colorectal carcinogenesis. Thus, we analyzed 200 mitogenomes from
      normal and cancer tissues of 100 colorectal cancer patients. Minority variant
      mutations were detected at the 1% level. We showed that somatic mutations
      frequently occur in colorectal cancer cells (75%) and are randomly distributed
      across the mitochondrial genome. Mutational signatures of somatic mitogenome
      mutations suggest that they might arise through nucleotide deamination due to
      oxidative stress. The majority of somatic mutations localized within the coding
      region (in positions not known from the human phylogeny) and was potentially
      pathogenic to cell metabolism. Further analysis suggested that the relaxation of
      negative selection in the mitogenomes of colorectal cancer cells may allow
      accumulation of somatic mutations. Thus, a shift in glucose metabolism from
      oxidative phosphorylation to glycolysis may create advantageous conditions for
      accumulation of mtDNA mutations. Considering the fact that the presence of
      somatic mtDNA mutations was not associated with any clinicopathological features,
      we suggested that mtDNA somatic mutations are "passengers" rather than the cause
      of colorectal carcinogenesis.

PMID- 29330894
TI  - Structure, function and evolution of the hemerythrin-like domain superfamily.
AB  - Hemerythrin-like proteins have generally been studied for their ability to
      reversibly bind oxygen through their binuclear nonheme iron centers. However, in
      recent years, it has become increasingly evident that some members of the
      hemerythrin-like superfamily also participate in many other biological processes.
      For instance, the binuclear nonheme iron site of YtfE, a hemerythrin-like protein
      involved in the repair of iron centers in Escherichia coli, catalyzes the
      reduction of nitric oxide to nitrous oxide, and the human F-box/LRR-repeat
      protein 5, which contains a hemerythrin-like domain, is involved in intracellular
      iron homeostasis. Furthermore, structural data on hemerythrin-like domains from
      two proteins of unknown function, PF0695 from Pyrococcus furiosus and NMB1532
      from Neisseria meningitidis, show that the cation-binding sites, typical of
      hemerythrin, can be absent or be occupied by metal ions other than iron. To
      systematically investigate this functional and structural diversity of the
      hemerythrin-like superfamily, we have collected hemerythrin-like sequences from a
      database comprising fully sequenced proteomes and generated a cluster map based
      on their all-against-all pairwise sequence similarity. Our results show that the
      hemerythrin-like superfamily comprises a large number of protein families which
      can be classified into three broad groups on the basis of their cation
      coordinating residues: (a) signal-transduction and oxygen-carrier hemerythrins (H
      HxxxE-HxxxH-HxxxxD); (b) hemerythrin-like (H-HxxxE-H-HxxxE); and, (c) metazoan F
      box proteins (H-HExxE-H-HxxxE). Interestingly, all but two hemerythrin-like
      families exhibit internal sequence and structural symmetry, suggesting that a
      duplication event may have led to the origin of the hemerythrin domain.

PMID- 29330896
TI  - Goodbye to neuromuscular images.

PMID- 29330895
TI  - Effect of local scrotal heating on the expression of tight junction-associated
      molecule Occludin in boar testes.
AB  - The aim of this study was to determine whether local scrotal heating (42 degrees
      C, for 1 hr) had an effect on the expression of tight junction (TJ)-associated
      molecule Occludin in boar testes. Adult boars (Landrace, n = 6) were used and
      randomly divided into two groups (n = 3 each). Three boars were given local
      scrotal exposure to 42 degrees C for approximately 1 h with a home-made electric
      blanket of controlled temperature as local scrotal heating group, the other three
      boars received no heat treatment and were left at standard room temperature as
      control group. After 6 hr, all boars were castrated and the testes were
      harvested. qRT-PCR, Western blotting and immunohistochemistry were used to
      explore the expression and localization of Occludin. qRT-PCR and Western blotting
      showed that the protein and mRNA levels of Occludin significantly decreased in
      local scrotal heating group as compared to the control. Furthermore,
      immunoreactivity staining of Occludin was localized at the sites of the blood
      testis barrier (BTB) and formed an almost consecutive and strong immunoreactivity
      strand in the control, while Occludin was limited to Sertoli cells (SCs) and no
      obvious immunoreactivity strand was present in local scrotal heating group. These
      data indicated that local scrotal heating decreased the expression of TJ
      associated molecule Occludin, which may be involved in heat-induced
      spermatogenesis damage.

PMID- 29330897
TI  - Cyclodextrin-assisted dispersive liquid-liquid microextraction for the
      preconcentration of carbamazepine and clobazam with subsequent sweeping micellar
      electrokinetic chromatography.
AB  - A new version of dispersive liquid-liquid microextraction, namely, cyclodextrin
      assisted dispersive liquid-liquid microextraction, with subsequent sweeping
      micellar electrokinetic chromatography has been developed for the
      preconcentration and sensitive detection of carbamazepine and clobazam. alpha
      Cyclodextrin and chloroform were used as the dispersive agent and extraction
      solvent, respectively. After the extraction, carbamazepine and clobazam were
      analyzed using micellar electrokinetic chromatography with ultraviolet detection.
      The detection sensitivity was further enhanced using the sweeping technique.
      Under optimal extraction and stacking conditions, the calibration curves of
      carbamazepine and clobazam were linear over a concentration range of 2.0-200.0
      ng/mL. The method detection limits at a signal-to-noise ratio of 3 were 0.6 and
      0.5 ng/mL with sensitivity enhancement factors of 3575 and 4675 for carbamazepine
      and clobazam, respectively. This developed method demonstrated high sensitivity
      enhancement factors and was successfully applied to the determination of
      carbamazepine and clobazam in human urine samples. The precision and accuracy for
      urine samples were less than 4.2 and 6.9%, respectively.

PMID- 29330898
TI  - Determination of phthalate esters in soil using a quick, easy, cheap, effective,
      rugged, and safe method followed by GC-MS.
AB  - A quick, easy, cheap, effective, rugged, and safe procedure was designed to
      extract pesticide residues from fruits and vegetables with a high percentage of
      water. It has not been used extensively for the extraction of phthalate esters
      from sediments, soils, and sludges. In this work, this procedure was combined
      with gas chromatography with mass spectrometry to determine 16 selected phthalate
      esters in soil. The extraction efficiency of the samples was improved by
      ultrasonic extraction and dissolution of the soil samples in ultra-pure water,
      which promoted the dispersion of the samples. Furthermore, we have simplified the
      extraction step and reduced the risk of organic solvent contamination by
      minimizing the use of organic solvents. Different extraction solvents and clean
      up adsorbents were compared to optimize the procedure. Dichloromethane/n-hexane
      (1:1, v/v) and n-hexane/acetone (1:1, v/v) were selected as the extractants from
      the six extraction solvents tested. C18/primary secondary amine (1:1, m/m) was
      selected as the sorbent from the five clean-up adsorbents tested. The recoveries
      from the spiked soils ranged from 70.00 to 117.90% with relative standard
      deviation values of 0.67-4.62%. The proposed approach was satisfactorily applied
      for the determination of phthalate esters in 12 contaminated soil samples.

PMID- 29330899
TI  - Retrograde transmitral paravalvular leak closure through an antegrade transseptal
      approach: A novel technique.
AB  - Mitral paravalvular leak (PVL) remains a well-known complication after mitral
      valve replacement. Since the first report over 25 years ago, several catheter
      based PVL closure techniques have been described. Most of these comprise of
      either an antegrade transseptal approach, or a retrograde transaortic or
      transapical approach. We herein report a novel percutaneous mitral PVL closure
      technique that was safely and successfully performed after failed attempt using a
      conventional antegrade approach.

PMID- 29330900
TI  - Overexpression of microRNA408 enhances photosynthesis, growth, and seed yield in
      diverse plants.
AB  - The ability of a plant to produce grain, fruit, or forage depends ultimately on
      photosynthesis. There have been few attempts, however, to study microRNAs, which
      are a class of endogenous small RNAs post-transcriptionally programming gene
      expression, in relation to photosynthetic traits. We focused on miR408, one of
      the most conserved plant miRNAs, and overexpressed it in parallel in Arabidopsis,
      tobacco, and rice. The transgenic plants all exhibited increased copper content
      in the chloroplast, elevated abundance of plastocyanin, and an induction of
      photosynthetic genes. By means of gas exchange and optical spectroscopy analyses,
      we showed that higher expression of miR408 leads to enhanced photosynthesis
      through improving efficiency of irradiation utilization and the capacity for
      carbon dioxide fixation. Consequently, miR408 hyper-accumulating plants exhibited
      higher rate of vegetative growth. An enlargement of seed size was also observed
      in all three species overproducing miR408. Moreover, we conducted a 2-year-two
      location field trial and observed miR408 overexpression in rice significantly
      increased yield, which was primarily attributed to an elevation in grain weight.
      Taken together, these results demonstrate that miR408 is a positive regulator of
      photosynthesis and that its genetic engineering is a promising route for
      enhancing photosynthetic performance and yield in diverse plants.

PMID- 29330901
TI  - Floral contrivances and specialised pollination mechanism strongly influence
      mixed mating in Wrightia tomentosa (Apocynaceae).
AB  - Reproductive success of a plant species is largely influenced by the outcome of
      mating pattern in a population. It is believed that a significantly larger
      proportion of animal-pollinated plants have evolved a mixed-mating strategy, the
      extent of which may vary among species. It is thus pertinent to investigate the
      key contributors to mating success, especially to identify the reproductive
      constraints in depauperate populations of threatened plant species. We examined
      the contribution of floral architecture, pollination mechanism and breeding
      system on the extent of outcrossing rate in a near-threatened tree species,
      Wrightia tomentosa. The breeding system was ascertained from controlled
      pollination experiments. In order to determine outcrossing rate, 60 open
      pollinated progeny were analysed using an AFLP markers. Although the trees are
      self-compatible, herkogamy and compartmentalisation of pollen and nectar in
      different chambers of the floral tube effectively prevent spontaneous autogamy.
      Pollination is achieved through specialised interaction with moths. Differential
      foraging behaviour of settling moths and hawkmoths leads to different proportions
      of geitonogamous and xenogamous pollen on the stigma. However, most open
      pollinated progeny were the result of xenogamy (outcrossing rate, tm = 0.68). The
      study shows that floral contrivances and pollination system have a strong
      influence on mating pattern. The differential foraging behaviour of the
      pollinators causes deposition of a mixture of self- and cross-pollen to produce a
      mixed brood. Inbreeding depression and geitonogamy appear to play a significant
      role in sustaining mixed mating in this species.

PMID- 29330902
TI  - Conformers, properties, and docking mechanism of the anticancer drug docetaxel:
      DFT and molecular dynamics studies.
AB  - The conformational structures and properties of the anticancer drug docetaxel
      (DTX) are studied theoretically. A total of 3888 trial structures were initially
      generated by all combinations of internal single-bond rotamers and screened with
      the B3LYP/3-21G* method. A total of 31 unique conformers were further optimized
      at the B3LYP/6-311G* method. Their relative energies, dipole moments, rotational
      constants, and harmonic vibrational frequencies were predicted. Single-point
      relative energies were then determined at the M06-L/6-311G(2df,p) level. The UV
      spectrum of the lowest-lying DTX conformer in methanol was investigated with the
      TD-CAM-B3LYP/6-311 + G(2df,p) method. The 31 unique DTX structures are mainly
      docked at three different sites within beta-tubulin. Based on the results of
      molecular docking and double-float MD simulations, the lowest-lying DTX conformer
      consistently exhibits good docking performance with beta-tubulin. We identified
      the residues LYS299, ARG215, GLN294, LEU275, THR216, GLU290, PRO274, and THR276
      on beta-tubulin as active sites forming a binding pocket responsible for locking
      DTX within beta-tubulin to make the combination more stable. The RMSD values show
      that the predicted complexes are favorable, and the SASA analysis shows that the
      hydrophilic properties of DTX are better than paclitaxel. (c) 2018 Wiley
      Periodicals, Inc.

PMID- 29330903
TI  - Lack of correlation between pollen aperture number and environmental factors in
      pansies (Viola L., sect. Melanium Ging.) - pollen heteromorphism re-examined.
AB  - The development of different pollen morphs by one specimen - pollen
      heteromorphism - occurs in ca. one-third species of the genus Viola. Melanium
      section species (pansies) stand out in producing the widest range of apertures
      among Viola species. Aperture number decreases with elevation increase, and
      faster germination of five-aperturate pollen as compared with three-aperturate
      has previously been postulated. We re-examined pollen heteromorphism in the
      context of its viability, and made correlations with elevation (>1500 m a.s.l.
      versus <1500 m a.s.l.), soil type (metalliferous versus non-metalliferous; MET
      versus NMET) and chromosome number based on selected study criteria of ca. 20%
      karyologically and morphologically strongly differentiated but genetically
      closely related pansies. A total of 79% of analysed species were heteromorphic,
      forming three- to six-colp or ate pollen per individual flower. Mean aperture
      number and pollen viability were not affected by soil type (MET versus NMET).
      Mean aperture number was also not influenced by elevation or species chromosome
      number. Positive correlations were established between aperture number and pollen
      viability, negative between pollen viability and elevation (increasing altitude
      of 100 m decreased pollen viability by 0.4%) and lack of correlation between
      chromosome number and pollen viability. The varied frequencies of different
      pollen morphs among species are not under the general pressure of ecological
      conditions, as previously postulated for the species of Melanium section. Rather,
      this trait in pansies, similar to other floral characters (e.g. long, curved
      nectar spur, 'landing platform', posterior petals with nectar guides), is
      adaptive but dependent on the breeding system (inbreeding versus outbreeding) of
      the individual species.

PMID- 29330905
TI  - Evidence-based consensus on opportunistic infections in inflammatory bowel
      disease.

PMID- 29330904
TI  - Testing a chemical series inspired by plant stress oxylipin signalling agents for
      herbicide safening activity.
AB  - BACKGROUND: Herbicide safening in cereals is linked to a rapid xenobiotic
      response (XR), involving the induction of glutathione transferases (GSTs). The XR
      is also invoked by oxidized fatty acids (oxylipins) released during plant stress,
      suggesting a link between these signalling agents and safening. To examine this
      relationship, a series of compounds modelled on the oxylipins 12-oxophytodienoic
      acid and phytoprostane 1, varying in lipophilicity and electrophilicity, were
      synthesized. Compounds were then tested for their ability to invoke the XR in
      Arabidopsis and protect rice seedlings exposed to the herbicide pretilachlor, as
      compared with the safener fenclorim. RESULTS: Of the 21 compounds tested, three
      invoked the rapid GST induction associated with fenclorim. All compounds
      possessed two electrophilic carbon centres and a lipophilic group characteristic
      of both oxylipins and fenclorim. Minor effects observed in protecting rice
      seedlings from herbicide damage positively correlated with the XR, but did not
      provide functional safening. CONCLUSION: The design of safeners based on the
      characteristics of oxylipins proved successful in deriving compounds that invoke
      a rapid XR in Arabidopsis but not in providing classical safening in a cereal.
      The results further support a link between safener and oxylipin signalling, but
      also highlight species-dependent differences in the responses to these compounds.
      (c) 2018 The Authors. Pest Management Science published by John Wiley & Sons Ltd
      on behalf of Society of Chemical Industry.

PMID- 29330907
TI  - Tubular adenomas with clear cell change in the colorectum: A case with four
      lesions and a review of the literature.

PMID- 29330909
TI  - Catalytic and Atom-Economic Csp3 -Csp3 Bond Formation: Alkyl Tantalum Ureates for
      Hydroaminoalkylation.
AB  - Atom-economic and regioselective Csp3 -Csp3 bond formation has been achieved by
      rapid C-H alkylation of unprotected secondary arylamines with unactivated
      alkenes. The combination of Ta(CH2 SiMe3 )3 Cl2 , and a ureate N,O-chelating
      ligand salt gives catalytic systems prepared in situ that can realize high yields
      of beta-alkylated aniline derivatives from either terminal or internal alkene
      substrates. These new catalyst systems realize C-H alkylation in as little as one
      hour and for the first time a 1:1 stoichiometry of alkene and amine substrates
      results in high yielding syntheses of isolated amine products by simple
      filtration and concentration.

PMID- 29330908
TI  - Defining expanded areas in EBUS sampling: EBUS guided trans- and intra-pulmonary
      artery needle aspiration, with review of transvascular EBUS.
AB  - BACKGROUND: Endobronchial Ultrasound-guided Transbronchial Needle Aspiration
      (EBUS-TBNA) has revolutionized the diagnostic approach to mediastinal diseases.
      Lesions located lateral to the pulmonary artery (trans-PA, Station 5), or in the
      lumen of the PA (intra-PA) are in the 'blind-spot' of EBUS. OBJECTIVES: We
      describe a case series where EBUS guided trans-pulmonary or intra-pulmonary
      aspiration (EBUS-TIPNA) was used for diagnosis. METHODS: Retrospective analysis
      of 10 patients who had EBUS-TIPNA over 3 years in 2 centres. The inclusion
      criteria included patients with station 5 lesions, or intrapulmonary artery
      lesions, where no other option was possible. RESULTS: The study included 4 males
      and 6 females, mean age 52 years, with 7 trans-PA and 3 intra-PA lesions.
      Adequacy was seen in 10/10, and a definitive diagnosis was made in 9/10 patients.
      There were no procedure-related complications. CONCLUSION: EBUS-TIPNA can be done
      as a safe and successful procedure and adds to the armamentarium of Convex Probe
      EBUS (CP-EBUS), in carefully selected patients.

PMID- 29330906
TI  - Generating retinoic acid gradients by local degradation during craniofacial
      development: One cell's cue is another cell's poison.
AB  - Retinoic acid (RA) is a vital morphogen for early patterning and organogenesis in
      the developing embryo. RA is a diffusible, lipophilic molecule that signals via
      nuclear RA receptor heterodimeric units that regulate gene expression by
      interacting with RA response elements in promoters of a significant number of
      genes. For precise RA signaling, a robust gradient of the morphogen is required.
      The developing embryo contains regions that produce RA, and specific
      intracellular concentrations of RA are created through local degradation mediated
      by Cyp26 enzymes. In order to elucidate the mechanisms by which RA executes
      precise developmental programs, the kinetics of RA metabolism must be clearly
      understood. Recent advances in techniques for endogenous RA detection and
      quantification have paved the way for mechanistic studies to shed light on
      downstream gene expression regulation coordinated by RA. It is increasingly
      coming to light that RA signaling operates not only at precise concentrations but
      also employs mechanisms of degradation and feedback inhibition to self-regulate
      its levels. A global gradient of RA throughout the embryo is often found
      concurrently with several local gradients, created by juxtaposed domains of RA
      synthesis and degradation. The existence of such local gradients has been found
      especially critical for the proper development of craniofacial structures that
      arise from the neural crest and the cranial placode populations. In this review,
      we summarize the current understanding of how local gradients of RA are
      established in the embryo and their impact on craniofacial development.

PMID- 29330911
TI  - Prognostic significance of arterial stiffness and osteoprotegerin in patients
      with stable coronary artery disease.
AB  - BACKGROUND: Arterial stiffness and vascular calcification significantly
      contribute to coronary atherosclerosis progression. The prognostic value of
      increased arterial stiffness and vascular calcification in subjects with stable
      coronary artery disease (CAD) after percutaneous coronary intervention(PCI) is
      currently under question. MATERIALS AND METHODS: We randomly enrolled 262
      patients with stable CAD 1 month after successful PCI. Carotid-femoral pulse wave
      velocity (PWV) was measured as a well-established index of central aortic
      stiffness. Osteoprotegerin (OPG) plasma levels were measured as a biomarker of
      vascular calcification. Patients were followed up prospectively up to 52 months.
      The primary endpoint was the composite of death from cardiovascular causes,
      myocardial infarction, stroke or hospitalization for cardiovascular causes.
      RESULTS: During the follow-up period, 48 patients presented the primary composite
      endpoint. Subjects who presented the primary endpoint, compared to subjects free
      of cardiovascular events, had significantly increased PWV (9.45 +/- 2.19 m/s vs
      8.73 +/- 2.07 m/s, P = .04) and OPG levels (4.21 +/- 2.19 pmol/L vs 3.18 +/- 1.74
      pmol/L, P = .003). Survival analysis indicated that PWV predicted adverse cardiac
      events MACE (Hazard ratio = 1.29 95%CI: 1.07-1.57, P = .008) independently from
      confounders such as age, sex, smoking habits, ejection fraction, extent of
      coronary artery disease, hypertension and diabetes mellitus. Interestingly, for
      every increase in pulse wave velocity by 1 m/s, there is an anticipated increase
      in the risk of major adverse cardiovascular event (MACE) by 29%. CONCLUSIONS:
      These findings extend the current knowledge concerning the role of arterial
      stiffness as powerful biomarkers in cardiovascular disease. Measurement of PWV
      might have a role in ascertaining prognosis and managing treatment in patients
      with stable CAD after PCI.

PMID- 29330912
TI  - High-capacity protein A affinity chromatography for the fast quantification of
      antibodies: Two-wavelength detection expands linear range.
AB  - The high-throughput analysis of antibodies from processes can be enhanced when
      the linear range is expanded and sample preparation is kept to a minimum. We
      developed a fast chromatography method based on a hexameric variant of
      staphylococcal protein A immobilized on Toyopearl matrix, TSK 5 PW using two
      wavelengths. A protocol with 5 min runtime and a single-wavelength detection at
      280 nm yielded an upper limit of quantification of 2.10 mg/mL and a lower limit
      of quantification of 0.06 mg/mL. The optimized method with a runtime of 2 min and
      two-wavelength detection at 280 and 300 nm allowed us to span a valid
      concentration range of 0.01-5.20 mg/mL using two calibration curves. Sample
      selectivity was tested using mock supernatant mixed with antibody concentrations
      of 0.1-2.1 mg/mL, sample stability in the autosampler was shown for at least 24
      h. We also tested the capabilities of the method to determine purity of an
      antibody sample by calculating the ratio of peak area of elution to peak area of
      flow-through, which correlated well with the expected purity. The method will be
      very useful for process development and in-process control, spanning
      concentrations from seed fermentation to harvest and purification.

PMID- 29330913
TI  - The mechanism of diflufenican resistance and its inheritance in oriental mustard
      (Sisymbrium orientale L.) from Australia.
AB  - BACKGROUND: An oriental mustard population (P3) collected near Quambatook,
      Victoria was identified as being resistant to diflufenican by screening with the
      field rate (200 g a.i. ha-1 ) of the herbicide. The mechanism(s) of diflufenican
      resistance and its inheritance in this population were therefore investigated.
      RESULTS: Dose-response experiments confirmed that population P3 was 140-fold more
      resistant to diflufenican than susceptible populations, as determined by the
      comparison of 50% lethal (LD50 ) values. The phytoene desaturase (PDS) gene from
      five individuals each of the S1 [susceptible (S)] and P3 [resistant (R)]
      populations was sequenced, and a substitution of valine for leucine at position
      526 (Leu-526-Val) was detected in all five individuals of P3, but not in the S1
      population. Inheritance studies showed that diflufenican resistance is encoded in
      the nuclear genome and is dominant, as the response to diflufenican at 200 g a.i.
      ha-1 of F1 families was equivalent to that of the resistant biotype. The
      segregation of F2 phenotypes fitted a 3:1 inheritance model. Segregation of 42 F2
      individuals by genotype sequencing fitted a 1:2:1 (ss:Rs:RR) ratio. CONCLUSION:
      Resistance to diflufenican in oriental mustard is conferred by the Leu-526-Val
      mutation in the PDS gene. Inheritance of resistance is managed by a single gene
      with high levels of dominance. (c) 2018 Society of Chemical Industry.

PMID- 29330914
TI  - Stereodivergent Synthesis of Tetrahydrofuroindoles through Pd-Catalyzed
      Asymmetric Dearomative Formal [3+2] Cycloaddition.
AB  - A stereodivergent synthesis of tetrahydrofuroindoles through palladium-catalyzed
      asymmetric dearomative formal [3+2] cycloaddition of nitroindoles with
      epoxybutenes was developed. The polarity of the solvent was found to play a key
      role in the diastereoselectivity. In toluene, good to excellent yields (70-99 %),
      diastereoselectivity (87/13->95/5 d.r.), and enantioselectivity (85/15-94/6 e.r.)
      were obtained, regardless of the properties of the substituents on nitroindoles.
      In acetonitrile, tetrahydrofuroindoles of a different diastereoisomer were
      produced with good to excellent yields (75-98 %) and stereoselectivity (78/22
      93/7 d.r., 93/7-99/1 e.r.). Mechanistic studies were conducted to illustrate the
      origin of the diastereodivergency. The kinetic experiments indicate that the rate
      determining step of this reaction is different in different solvents. ESI-MS
      experiments also support the existence of key palladium complex intermediates and
      the catalytic cycle of the reaction.

PMID- 29330915
TI  - Effects of seed mixture sowing with resistant and susceptible rice on population
      dynamics of target planthoppers and non-target stemborers and leaffolders.
AB  - BACKGROUND: The widespread planting of insect-resistant crops has caused a
      dramatic shift in agricultural landscapes, thus raising concerns about the
      potential impact on both target and non-target pests worldwide. In this study, we
      examined the potential effects of six seed mixture ratios of insect-resistance
      dominance [100% (R100), 95% (S05R95), 90% (S10R90), 80% (S20R80), 60% (S40R60),
      and 0% (S100)] on target and non-target pests in a 2-year field trial in southern
      China. RESULTS: The occurrence of the target pests Nilaparvata lugens and
      Sogatella furcifera decreased with an increase in the ratio of resistant rice,
      and mixture ratios with >=90% resistant rice significantly increased the pest
      suppression efficiency, with the lowest occurrences of the non-target pests
      Sesamia inferens, Chilo suppressalis and Cnaphalocrocis medinalis for S100 and
      S10R90 seed mixture ratios. Furthermore, there were no significant differences in
      the 1000-grain dry weight and grain yield between R100 and other treatments with
      >=80% resistant seeds in the mixture (S20R80, S10R90 and S05R95). CONCLUSION:
      S10R90 produced a good yield and provided the most effective control of both
      target and non-target pests, with the potential to significantly reduce the
      application of chemical pesticides for integrated pest management in paddy
      fields. It is further presumed that the strategy of seed mixture with resistant
      and susceptible rice would be advantageous for rice yield stability. (c) 2018
      Society of Chemical Industry.

PMID- 29330916
TI  - Separation of three polar compounds from Rheum tanguticum by high-speed
      countercurrent chromatography with an ethyl acetate/glacial acetic acid/water
      system.
AB  - The separation of polar compounds by high-speed countercurrent chromatography is
      still regarded as a challenge. In this study, an efficient strategy for the
      separation of three polar compounds from Rheum tanguticum has been successfully
      conducted by using high-speed countercurrent chromatography. X-5 macroporous
      resin chromatography was used for the fast enrichment of the target compounds.
      Then, the target fraction was directly introduced into high-speed countercurrent
      chromatography for separation using ethyl acetate/glacial acetic acid/water
      (100:1:100, v/v/v) as the solvent system. Consequently, three polar compounds
      including gallic acid, catechin, and gallic acid 4-O-beta-d-(6'-O-galloyl)
      glucoside were obtained with purities higher than 98%. The results showed glacial
      acetic acid could be such an appropriate regulator for the ethyl acetate/water
      system. This study provides a reference for the separation of polar compounds
      from natural products by high-speed countercurrent chromatography.

PMID- 29330917
TI  - Mitochondrial respiratory capacity remains stable despite a comprehensive and
      sustained increase in insulin sensitivity in obese patients undergoing gastric
      bypass surgery.
AB  - AIM: It has been proposed, but not yet demonstrated by convincing evidence in
      published articles, that insulin resistance and mitochondrial respiratory
      function are causally related physiological phenomena. Here, we tested the
      prediction that weight loss-induced increase in insulin sensitivity will
      correlate with a corresponding change in mitochondrial respiratory capacity over
      the same time period. METHODS: Insulin sensitivity was evaluated using the
      hyperinsulinaemic-euglycaemic clamp technique, and skeletal muscle mitochondrial
      respiratory capacity was evaluated by high-resolution respirometry in 26 patients
      with obesity. Each experiment was performed ~2 months and 1-2 weeks before, and
      ~4 and ~19 months after Roux-en-Y gastric bypass (RYGB) surgery. RESULTS: A
      substantial weight loss was observed in all patients, and insulin sensitivity
      increased in all patients over the 21-months time period of the study. In
      contrast, skeletal muscle mitochondrial respiratory capacity, intrinsic
      mitochondrial respiratory capacity and mitochondrial content remained unchanged
      over the same time period. CONCLUSION: Among obese patients with and without type
      2 diabetes undergoing RYGB surgery, intrinsic mitochondrial respiratory capacity
      in skeletal muscle is not correlated with insulin sensitivity before or after the
      surgical intervention. Mitochondrial respiratory function may not be germane to
      the pathophysiology and/or aetiology of obesity and/or type 2 diabetes.

PMID- 29330918
TI  - Leptosphaeria maculans AvrLm9: a new player in the game of hide and seek with
      AvrLm4-7.
AB  - Blackleg disease of Brassica napus caused by Leptosphaeria maculans (Lm) is
      largely controlled by the deployment of race-specific resistance (R) genes.
      However, selection pressure exerted by R genes causes Lm to adapt and give rise
      to new virulent strains through mutation and deletion of effector genes.
      Therefore, a knowledge of effector gene function is necessary for the effective
      management of the disease. Here, we report the cloning of Lm effector AvrLm9
      which is recognized by the resistance gene Rlm9 in B. napus cultivar Goeland.
      AvrLm9 was mapped to scaffold 7 of the Lm genome, co-segregating with the
      previously reported AvrLm5 (previously known as AvrLmJ1). Comparison of AvrLm5
      alleles amongst the 37 re-sequenced Lm isolates and transgenic complementation
      identified a single point mutation correlating with the AvrLm9 phenotype.
      Therefore, we renamed this gene as AvrLm5-9 to reflect the dual specificity of
      this locus. Avrlm5-9 transgenic isolates were avirulent when inoculated on the B.
      napus cultivar Goeland. The expression of AvrLm5-9 during infection was monitored
      by RNA sequencing. The recognition of AvrLm5-9 by Rlm9 is masked in the presence
      of AvrLm4-7, another Lm effector. AvrLm5-9 and AvrLm4-7 do not interact, and
      AvrLm5-9 is expressed in the presence of AvrLm4-7. AvrLm5-9 is the second Lm
      effector for which host recognition is masked by AvrLm4-7. An understanding of
      this complex interaction will provide new opportunities for the engineering of
      broad-spectrum recognition.

PMID- 29330919
TI  - Meta-analysis of laparoscopic versus open liver resection for hepatocellular
      carcinoma.
AB  - AIM: The aim of this study was to evaluate the surgical safety and effectiveness
      of laparoscopic hepatectomy (LH) in short- and long-term outcomes compared to
      open hepatectomy (OH) in patients treated for hepatocellular carcinoma (HCC).
      METHODS: An electronic search of reports published before August 2017 was carried
      out to identify comparative studies evaluating LH versus OH for HCC. RESULTS: A
      total of 5889 patients (2421 underwent LH; 3468 underwent OH) were included in
      our meta-analysis from 47 studies. Laparoscopic hepatectomies were associated
      with favorable outcomes in terms of operative blood loss (mean difference [MD], 
      147.27; 95% confidence interval [CI], -217.00, -77.55), blood transfusion
      requirement (odds ratio [OR], 0.51; 95% CI, 0.40, 0.65), pathologic resection
      margins (MD, 0.07; 95% CI, 0.02, 0.12; P = 0.01), R0 resection rate (OR, 1.34;
      95% CI, 0.98, 1.84; P = 0.07), and length of hospital stay (MD, -5.13; 95%
      confidence interval, -6.23, -4.03). There were no differences between the groups
      in overall survival (OS) at 1 year (OR, 1.41; 95% CI, 1.00, 1.98), 3 years (OR,
      1.12; 95% CI, 0.93, 1.36), or 5 years (OR, 1.18; 95% CI, 0.94, 1.46), in disease
      free survival (DFS) at 1 (OR, 1.19; 95% CI, 0.94, 1.51), 3 years (OR, 1.07; 95%
      CI, 0.86, 1.33), or 5 years (OR, 1.13; 95% CI, 0.92, 1.40), or in recurrence (OR,
      0.90; 95% CI, 0.74, 1.08). CONCLUSION: Compared to OH, LH is superior in terms of
      lower intraoperative blood loss and the requirement for blood transfusion, larger
      pathologic resection margins, increased R0 resection rates, and shorter length of
      hospital stay. Laparoscopic hepatectomy and OH have similar OS, DFS, and
      recurrence.

PMID- 29330920
TI  - Macronutrient and fibre intake of young Spanish children with reference to their
      in utero growth status: Are they eating a healthy diet?
AB  - AIM: To compare macronutrient and fibre intake by pre-school children born with
      intra-uterine growth restriction (IUGR) or as appropriate for gestational age
      (AGA) and to compare their intake with paediatric nutritional recommendations for
      identification of potential areas of modification during early life. METHODS: A
      parental 3-day dietary record was obtained for children of age 1-6 years, born at
      Hospital Clinic, Barcelona, Spain (2002-2007) with IUGR (n = 37) or AGA (n = 53).
      Mean nutrient intake (adjusted for body mass index), nutrient adequacy ratios
      (NAR) and percentage of energy intake (EI%) were compared. RESULTS: Macronutrient
      and fibre intake of the two groups did not differ significantly. However, IUGR
      children showed significantly higher than the recommended levels of protein EI%
      (18 (95% confidence interval (CI) 16-19)), NAR for saturated fatty acids (SFAs)
      (1.2 (95% CI 1.1-1.5)) and NAR for carbohydrate (1.4 (95% CI 1.2-1.6)) and
      significantly lower than the recommended levels of NAR for unsaturated fatty
      acids (UFAs) (0.6 (95% CI 0.5-0.8)) and for fibre (0.6 (95% CI 0.5-0.8)).
      Likewise, children born with AGA showed similar pattern compared to the
      recommended levels for protein EI% (17 (95% CI 16-18)), NAR for SFAs (1.3 (95% CI
      1.2-1.4)), NAR for UFAs (0.6 (95% CI 0.5-0.7)) and NAR for fibre (0.8 (95% CI 0.7
      0.9)). CONCLUSION: Spanish pre-school children consume proteins and SFAs in
      abundance and UFAs and fibre in moderation. Reinforcement of healthy eating is
      recommended for long-term health benefits, especially for at-risk children born
      with IUGR, whose consumption of carbohydrate is additionally greater than that
      recommended.

PMID- 29330921
TI  - Four and a half domain 2 (FHL2) scaffolding protein is a marker of connective
      tissues of developing digits and regulates fibrogenic differentiation of limb
      mesodermal progenitors.
AB  - Four and a half LIM domain 2 (FHL2) is a multifunctional scaffolding protein of
      well-known function regulating cell signalling cascades and gene transcription in
      cancer tissues. However, its function in embryonic systems is poorly
      characterized. Here, we show that Fhl2 is involved in the differentiation of
      connective tissues of developing limb autopod. We show that Fhl2 exhibits
      spatially restricted and temporally dynamic expression around the tendons of
      developing digits, interphalangeal joint capsules, and fibrous peridigital
      tissue. Immunolabelling analysis of the skeletal progenitors identified a
      predominant, but not exclusive, cytoplasmic distribution of FHL2 being associated
      with focal adhesions and actin cytoskeleton. In the course of chondrogenic
      differentiation of cultures of limb skeletal progenitors, the expression of Fhl2
      is down-regulated. Furthermore, cultures of skeletal progenitors overexpressing
      Fhl2 take on a predominant fibrogenic appearance. Both gain-of-function and loss
      of-function experiments in the micromass culture assays revealed a positive
      transcriptional influence of Fhl2 in the expression of fibrogenic markers
      including Scleraxis, Tenomodulin, Tenascin C, betaig-h3, and Tgif1. We further
      show that the expression of Fhl2 is positively regulated by profibrogenic signals
      including Tgfbeta2, all-trans-retinoic acid, and canonical Wnt signalling
      molecules and negatively regulated by prochondrogenic factors of the bone
      morphogenetic protein family. Expression of Fhl2 is also regulated negatively in
      immobilized limbs, but this influence appears to be mediated by other connective
      tissue markers, such as Tgfbetas and Scleraxis.

PMID- 29330922
TI  - 2018 message from the editor in chief-Movement Disorders journal at cruise speed.

PMID- 29330923
TI  - Mutant parkin-induced parkinsonism from an electrical point of view: Abnormal
      excitatory response to dopamine resolved after substitution.

PMID- 29330924
TI  - Erratum.

PMID- 29330925
TI  - In Situ Growth of MnO2 Nanosheets on N-Doped Carbon Nanotubes Derived from
      Polypyrrole Tubes for Supercapacitors.
AB  - Nitrogen-doped porous carbon nanotubes@MnO2 (N-CNTs@MnO2 ) nanocomposites are
      prepared through the in situ growth of MnO2 nanosheets on N-CNTs derived from
      polypyrrole nanotubes (PNTs). Benefiting from the synergistic effects between N
      CNTs (high conductivity and N doping level) and MnO2 nanosheets (high theoretical
      capacity), the as-prepared N-CNTs@MnO2 -800 nanocomposites show a specific
      capacitance of 219 F g-1 at a current density of 1.0 A g-1 , which is higher than
      that of pure MnO2 nanosheets (128 F g-1 ) and PNTs (42 F g-1 ) in 0.5 m Na2 SO4
      solution. Meanwhile, the capacitance retention of 86.8 % (after 1000 cycles at 10
      A g-1 ) indicates an excellent electrochemical performance of N-CNTs@MnO2
      prepared in this work.

PMID- 29330926
TI  - Detection of bovine Deltapapillomavirus DNA in peripheral blood of healthy sheep
      (Ovis aries).
AB  - Blood samples from 65 sheep were tested for the presence of bovine
      Deltapapillomavirus (deltaPVs) DNA. The sheep were divided into three groups.
      Sheep in groups 1 and 2 were from Sardinia and Campania, respectively, and were
      in contact with cattle and grazed on lands contaminated with bracken fern. Sheep
      in Group 3 lived in closed pens and had no contact with cattle. These sheep were
      fed hay that did not contain bracken fern. Bovine deltaPV E5 DNA was detected in
      blood from 24 of 27 (89%) sheep in Group 1. A single bovine deltaPV type was
      detected in the blood from nine (33%) sheep, including the detection of bovine
      deltaPV-1 DNA in four sheep, bovine deltaPV-2 in four and deltaPV-13 in one
      sheep. Two deltaPV types were detected in 33% of the sheep, and three bovine
      deltaPV types were detected in 22% of the sheep. Bovine deltaPVs were detected in
      17 of 20 (85%) sheep from Group 2. The detection rate by a single deltaPV type
      was 40% with just deltaPV-1 DNA amplified from two, just deltaPV-2 DNA from four,
      and just deltaPV-13 DNA from two sheep. Two and three deltaPVs were detected in
      30% and 15%, respectively. All sequenced amplicons showed a 100% identity with
      papillomaviral E5 DNA deposited in GenBank. Bovine deltaPV-14 DNA sequences were
      not detected from any sheep. No bovine deltaPV DNA was revealed in blood samples
      from sheep in Group 3. The detection of bovine deltaPV DNA in the blood of sheep
      means that sheep may be able to be infected by these PVs. This suggests that
      bovine deltaPVs could potentially be a previously unrecognized cause of disease
      in sheep. Furthermore, it is possible that sheep could act as a reservoir for
      these viruses.

PMID- 29330927
TI  - Defined Serum-Free Medium for Bioreactor Culture of an Immortalized Human
      Erythroblast Cell Line.
AB  - Anticipated shortages in donated blood supply have prompted investigation of
      alternative approaches for in vitro production of red blood cells (RBCs), such as
      expansion of conditional immortalization erythroid progenitors. However, there is
      a bioprocessing challenge wherein factors promoting maximal cell expansion and
      growth-limiting inhibitory factors are yet to be investigated. The authors use an
      erythroblast cell line (ImEry) derived from immortalizing CD71+CD235a+
      erythroblast from adult peripheral blood for optimization of expansion culture
      conditions. Design of experiments (DOE) is used in media formulation to explore
      relationships and interactive effects between factors which affect cell
      expansion. Our in-house optimized medium formulation produced significantly
      higher cell densities (3.62 +/- 0.055) * 106  cells mL-1 , n = 3) compared to
      commercial formulations (2.07 +/- 0.055) * 106  cells mL-1 , n = 3; at 209 h
      culture). Culture media costs per unit of blood is shown to have a 2.96-3.09
      times cost reduction. As a proof of principle for scale up, ImEry are expanded in
      a half-liter stirred-bioreactor under controlled settings. Growth
      characteristics, metabolic, and molecular profile of the cells are evaluated.
      ImEry has identical O2 binding capacity to adult erythroblasts. Amino acid
      supplementation results in further yield improvements. The study serves as a
      first step for scaling up erythroblast expansion in controlled bioreactors.

PMID- 29330928
TI  - Specific labelling of myonuclei by an antibody against pericentriolar material 1
      on skeletal muscle tissue sections.
AB  - AIM: Skeletal muscle is a heterogeneous tissue containing several different cell
      types, and only about 40%-50% of the cell nuclei within the tissue belong to
      myofibres. Existing technology, attempting to distinguish myonuclei from other
      nuclei at the light microscopy level, has led to controversies in our
      understanding of the basic cell biology of muscle plasticity. This study aims at
      demonstrating that an antibody against the protein pericentriolar material 1
      (PCM1) can be used to reliably identify myonuclei on histological cross sections
      from humans, mice and rats. METHODS: Cryosections were labelled with a polyclonal
      antibody against PCM1. The specificity of the labelling for myonuclei was
      verified using 3D reconstructions of confocal z-stacks triple-labelled for DNA,
      dystrophin and PCM1, and by co-localization with nuclear mCherry driven by the
      muscle-specific Alpha-Actin-1 promoter after viral transduction. RESULTS: The
      PCM1 antibody specifically labelled all myonuclei, and myonuclei only, in
      cryosections of muscles from rats, mice and men. Nuclei in other cell types
      including satellite cells were not labelled. Both normal muscles and hypertrophic
      muscles after synergist ablation were investigated. CONCLUSION: Pericentriolar
      material 1 can be used as a specific histological marker for myonuclei in
      skeletal muscle tissue without relying on counterstaining of other structures or
      cumbersome and subjective analysis of nuclear positioning.

PMID- 29330929
TI  - Adipocytes affect castration-resistant prostate cancer cells to develop the
      resistance to cytotoxic action of NK cells with alterations of PD-L1/NKG2D ligand
      levels in tumor cells.
AB  - BACKGROUND: Obesity affects prostate cancer (PCa) progression, and the
      periprostatic adipose tissue adjacent to the prostate is considered a driving
      force of disease progression. Adipocytes are the main cell population in adipose
      tissues and their paracrine role contributes to PCa progression, however its
      implication in modulating immune reactions remains largely unknown. We
      investigated the adipocyte role in controlling the susceptibility of castration
      resistant PCa (CRPC) cells to the cytotoxic action of natural killer (NK) cells.
      METHODS: Using primary NK cells as the NK cell source, NK cell cytotoxicities to
      CRPC cells, either control media treated or adipocyte-conditioned media (CM)
      treated, were tested in lactate dehydrogenase (LDH) release-based assays. The
      levels of programmed death receptor ligand (PD-L1) and NK group 2D (NKG2D)
      ligands in adipocyte CM-treated CRPC cells were analyzed in qPCR analyses.
      Effects of blocking adipocyte action on altering PD-L1/NKG2D ligand levels and
      the susceptibility of CRPC cells to NK cell cytotoxicity were investigated.
      RESULTS: We found NK cell cytotoxicity to CRPC cells decreases when tumor cells
      are treated with adipocyte CM associated with PD-L1 and NKG2D ligand level
      alterations. Further, we discovered that the JAK/Stat3 signaling pathway was
      responsible for the adipocyte CM effect. Two adipokine molecules, IL-6 and
      leptin, were shown to be important in activation of the JAK/Stat3 signaling in
      CRPC cells to modulate the PD-L1/NKG2D ligand level alteration. Adding the
      inhibitors of JAK/Stat3 signaling or neutralizing antibodies of IL-6 or leptin
      increased the susceptibility of CRPC cells to NK cell action. CONCLUSIONS:
      Blocking the adipocyte effect by inhibiting the IL-6/leptin-JAK/Stat3 signaling
      axis may enhance NK cell mediated immunity to CRPC cells and this strategy may
      help to develop future therapeutics to treat obese PCa patients.

PMID- 29330930
TI  - Gender-specific risk factors for androgenetic alopecia in the Korean general
      population: Associations with medical comorbidities and general health behaviors.
AB  - BACKGROUND: The relationships between androgenetic alopecia (AGA) and various
      factors related to metabolic syndrome have been demonstrated in previous studies.
      However, it remains unclear because of inconsistent results. We investigated the
      associations between AGA and various risk factors related to metabolic syndrome
      according to gender. METHODS: We conducted a population-based cross-sectional
      survey of 2028 Koreans (1050 men, 978 women). The basic and specific (BASP)
      classification was used for diagnosis of AGA. We collected information on risk
      factors though questionnaires and medical records. RESULTS: AGA was significantly
      associated with age, family history of AGA, hypertension, diabetes mellitus, and
      waist circumference in both genders. Female subjects with AGA were more likely to
      have cerebrovascular disease, dyslipidemia, and obesity; however, these
      associations were not observed in the male subjects. When multiple regression
      analysis was applied, there was a significant relationship between hypertension
      and AGA in male subjects. However, there was no statistically significant
      association in female subjects. CONCLUSION: The different results according to
      gender might arise from different mechanisms of AGA. There was a significant
      relationship between hypertension and AGA in male subjects. Evaluation of blood
      pressure in male patients with AGA might facilitate interventions for
      hypertension.

PMID- 29330931
TI  - Teaching & Learning Tips 4: Motivation and emotion in learning.
AB  - Challenge: Trainees' motivational and emotional states can influence their
      learning and career decisions, but historically these "affective" learning
      factors have received little attention in medical education. In this "Tips"
      piece, we outline strategies to positively influence trainees' intrinsic
      motivation and emotion toward their training to ultimately enhance their overall
      learning experience.

PMID- 29330932
TI  - Influences for gender disparity in dermatology in North America.
AB  - BACKGROUND: Despite constituting half the population, women represent a minority
      of active physicians and hold a small proportion of faculty leadership positions
      in North America. However, dermatology is one of the few specialties where women
      comprise a substantial portion of the workforce. This study explores extent and
      contributors to gender disparity in academic dermatology faculty positions,
      leadership, and research. METHODS: We collected data on academic faculty
      including leadership from the websites of accredited U.S. and Canadian
      dermatology faculties. We used PubMed and SCOPUS to collect faculty research
      information including h-index, number of publications, citations, and years of
      active research. RESULTS: Although women constitute almost half of all
      dermatologists in the U.S. and Canada (47.9%), only one-fourth (26.1%) of all
      faculty heads are women. Furthermore, the proportion of women in higher faculty
      ranks (Assistant Professor, Associate Professors, and Professors) is much lower
      than males. Female dermatologists also have fewer publications, citations, and
      years of active research. Interestingly, having a female in a leadership position
      is associated with a higher proportion of female dermatologists in the faculty.
      CONCLUSIONS: Gender disparity exists in academic dermatology, and the current
      academics fail to account for the enormous social challenges that women face,
      which may put them at a disadvantage to career advancement. Among other factors,
      better representation of female leadership may encourage and inspire women
      joining academic faculties in the future.

PMID- 29330933
TI  - To avoid a misleading genetic diagnosis of epidermolysis bullosa.

PMID- 29330934
TI  - Melatonin inhibits the proliferation of breast cancer cells induced by bisphenol
      A via targeting estrogen receptor-related pathways.
AB  - BACKGROUND: Background: Bisphenol A (BPA) is an estrogen-like chemical widely
      contained in daily supplies. There is evidence that environmental exposure to BPA
      could contribute to the development of hormone-related cancers. As is reported in
      numerous studies, melatonin, an endogenous hormone secreted by the pineal gland,
      could markedly inhibit estrogen-induced proliferation of breast cancer (BC)
      cells. In this study, we intended to reveal the effects of melatonin on BPA
      induced proliferation of estrogen receptor-positive BC cells. METHODS: Methods:
      We used methyl thiazolyl tetrazolium, luciferase reporter gene and western
      blotting assays to testify the effect of melatonin on BPA-mediated proliferation
      of MCF-7 and T47D cells. RESULTS: Methyl thiazolyl tetrazolium and colony
      formation assays showed that melatonin could significantly abolish BPA-elevated
      cell proliferation. Meanwhile, BPA-upregulated phosphorylation of ERK and AKT was
      decreased by melatonin treatment. Mechanistically, we found that BPA was capable
      of upregulating the protein levels of steroid receptor coactivators (SRC-1, SRC
      3), as well as promoting the estrogen response element activity. However, the
      addition of melatonin could remarkably block the elevation of steroid receptor
      coactivators expression and estrogen response element activity triggered by BPA.
      CONCLUSION: Conclusions: Therefore, these results demonstrated that melatonin
      could abrogate BPA-induced proliferation of BC cells. Therapeutically, melatonin
      could be regarded as a potential medication for BPA-associated BC.

PMID- 29330935
TI  - Takotsubo cardiomyopathy in a young adult with transplanted heart: what happened
      to denervation?
AB  - This manuscript describes the first report of takotsubo cardiomyopathy in a young
      heart transplant recipient following angry debate. Our patient is a 21-year-old
      woman with cardiac transplant performed owing to right ventricular failure in
      congenital heart disease. Positive echocardiography with typical asymmetry of
      regional function, positive enzymes, and negative biopsy and angiography met the
      criteria for the diagnosis of takotsubo cardiomyopathy. Patient was discharged
      after 1 week in good clinical conditions and fully recovered cardiac function.
      The development of takotsubo cardiomyopathy in transplanted heart suggests that
      re-innervation occurs, thus representing a target for catecholamine-induced
      cardiac dysfunction.

PMID- 29330936
TI  - Give me a sample of air and I will tell which species are found from your region:
      Molecular identification of fungi from airborne spore samples.
AB  - Fungi are a megadiverse group of organisms, they play major roles in ecosystem
      functioning and are important for human health, food production and nature
      conservation. Our knowledge on fungal diversity and fungal ecology is however
      still very limited, in part because surveying and identifying fungi is time
      demanding and requires expert knowledge. We present a method that allows anyone
      to generate a list of fungal species likely to occur in a region of interest,
      with minimal effort and without requiring taxonomical expertise. The method
      consists of using a cyclone sampler to acquire fungal spores directly from the
      air to an Eppendorf tube, and applying DNA barcoding with probabilistic species
      identification to generate a list of species from the sample. We tested the
      feasibility of the method by acquiring replicate air samples from different
      geographical regions within Finland. Our results show that air sampling is
      adequate for regional-level surveys, with samples collected >100 km apart varying
      but samples collected <10 km apart not varying in their species composition. The
      data show marked phenology, and thus obtaining a representative species list
      requires aerial sampling that covers the entire fruiting season. In sum, aerial
      sampling combined with probabilistic molecular species identification offers a
      highly effective method for generating a species list of air-dispersing fungi.
      The method presented here has the potential to revolutionize fungal surveys, as
      it provides a highly cost-efficient way to include fungi as a part of large-scale
      biodiversity assessments and monitoring programs.

PMID- 29330937
TI  - First-time detection of porcine reproductive and respiratory syndrome virus
      (PRRSV) infection in Uruguay.
AB  - Within the last two decades, several high-impact viruses have emerged in the
      global swine population, including porcine reproductive and respiratory syndrome
      virus (PRRSV). In Uruguay, the more recent serological survey for PRRSV and other
      notifiable diseases such as Aujeszky's disease virus (ADV) and classical swine
      fever virus (CSFV) dated from year 2000. The main purpose of this study was to
      update our information on the infection status of PRRSV, ADV and CSFV in
      Uruguayan pig herds, in order to keep informed about the epidemiological
      situation of these notifiable infections in the country. For serological testing,
      a total of 524 swine serum samples collected during the period 2014-2016 were
      assayed by commercial ELISAs. Our results revealed the (unexpected) presence of
      PRRSV antibodies in Uruguayan domestic swine herds and confirmed the absence of
      ADV and CSFV antibodies in all of the assessed samples. Following such initial
      finding, PRRSV antibodies were further investigated in 23 retrospective samples
      collected during 2010-2014. Thirteen of these 23 samples resulted seropositive.
      Subsequently, a molecular detection approach in frozen serum samples was
      implemented to confirm PRRSV infection, and viral RNA was identified by reverse
      transcription-nested polymerase chain reaction (RT-nPCR). Fourteen of 86
      evaluated 2014-2016 samples resulted positive for viral RNA, while molecular
      analysis of four retrospective samples also revealed the presence of PRRSV type
      2. Viral isolation of selected samples was carried out in porcine alveolar
      macrophages (PAM) and MARC 145 simian kidney cells, and the virus identity was
      confirmed by cytopathic effect (CPE) and immunofluorescence assay (IFA) using
      specific monoclonal antibodies for PRRSV nucleocapsid. Data reported here
      evidence for the first time the circulation of PRRSV type 2 in Uruguay, and
      retrospective serology results suggest that the virus has been infecting pigs in
      this country at least since 2011.

PMID- 29330938
TI  - Predictive value of neutrophil to lymphocyte ratio in long-term outcomes of left
      main and/or three-vessel disease in patients with acute myocardial infarction.
AB  - OBJECTIVES: We sought to evaluate the independent predictive value of left main
      disease (LMD) and/or three-vessel disease (LMD/3VD) in acute myocardial
      infarction (AMI) patients. BACKGROUND: Patients with acute coronary syndrome
      resulting from LMD and/or three-vessel disease (LMD/3VD) are at the highest risk
      of adverse cardiovascular events. Neutrophil to lymphocyte ratio (NLR) has been
      proposed as a marker of cardiovascular risk, but the prognostic value of NLR in
      patients with LMD/3VD who underwent percutaneous coronary intervention (PCI) is
      not clearly defined. METHODS: Patients (n = 806) admitted with LMD/3VD who
      underwent PCI between January 2013 and December 2013 were followed up for 2
      years. Admission NLR was divided into two sub-groups based on an optimal cut off
      value predicting 2-year all-cause mortality. The primary end point was all-cause
      death. The secondary end point was long-term major adverse cardiovascular and
      cerebrovascular events (MACCE). RESULTS: During follow-up, the high NLR group was
      associated with a significantly higher rate of long-term all-cause mortality (6.7
      vs. 0.9%, P < .001), and MACCE (24.7 vs. 15.8%, P = .002) compared to the low NLR
      group. In multivariate analysis, after adjusting for risk factors, NLR >= 3.39
      was determined to be an independent predictor of 2-year all-cause mortality
      (hazard ratio[HR] 3.08, 95% confidence interval [CI] 1.06 to 8.97, P = .039) and
      MACCE (hazard ratio 1.44, 95% CI 1.01 to 2.05, P = .046) for LMD/3VD.
      CONCLUSIONS: The admission NLR as relatively inexpensive marker of inflammation
      may aid in the risk stratification and prognosis of patients diagnosed with
      LMD/3VD.

PMID- 29330939
TI  - Corrigendum.

PMID- 29330940
TI  - Extracorporeal shockwave therapy for treatment of keloid scars.
AB  - The purpose of this investigation was to study the effectiveness of
      extracorporeal shockwave therapy (ESWT) for the treatment of keloid scars, and
      compared the results with intralesional steroid injection. Thirty-nine patients
      were randomly divided into 22 in ESWT group and 17 in steroid group. The ESWT
      group received 3 ESWT treatments in 6 weeks. The steroid group received three
      intra-lesional triamcinolone injections in 6 weeks. The evaluations included
      gross morphology, functional outcome, local blood flow perfusion, biopsy for
      histopathological examination, and immunohistochemical analysis. Both groups
      showed significant improvements in appearance with less discoloration, flattening
      and softer consistency, and more elasticity of the lesions. There is a
      significant reduction in keloid height after treatment in both groups, and
      significant differences are noticed between two groups after treatment. The
      volume of keloid was decreased after treatment but there is no statistically
      significant difference between two groups. Both groups showed comparable
      functional scores, POSAS patient, and observer scales. The blood flow perfusion
      rates were statistically not significant between two groups before and after
      treatments. Histopathological findings revealed no significant difference in cell
      count, cell activity, and cell concentration between two groups. After ESWT, the
      significant decreases in collagen type I, type III, and Masson Trichrome stain
      were observed as compared with steroid group. However, very little changes were
      noticed in angiogenesis, inflammatory cytokines, proliferating and regeneration,
      and apoptosis, with no statistical significance noticed between two groups before
      and after treatment. This study revealed that ESWT showed comparable functional
      outcome and POSAS patient and observer scales as compared with steroid injection
      for keloid scars. Treatment of keloid scars with ESWT resulted in significant
      decreases in collagen fibers and increases in MMP-13 enzyme.

PMID- 29330941
TI  - Hydrophobic and hydrophilic effects on water structuring and adhesion in denture
      adhesives.
AB  - Denture adhesives are designed to be moisture-sensitive through the inclusion of
      a blend of polymer salts with varying degrees of water-sensitivity. This enables
      the adhesive to mix with saliva in vivo and activate its high tack, through the
      formation of a mucilaginous layer. We report for the first time, the use of
      differential scanning calorimetry to study a series of hydrophobic and
      hydrophilic polymeric systems in order to correlate water-structuring behavior
      with adhesion strength. Adhesive bonding of the more hydrophobic variants was
      higher than that of a commercial-based control and a more hydrophilic polymer
      system in both lap shear and tensile configurations. Water-binding data suggested
      that increasing the hydrophobicity of the maleic acid copolymer substituents led
      to decreased levels of freezing water. In comparison, increasing the hydrophilic
      nature of the polymer backbone gave higher levels of freezing water within the
      hydrated samples. The results of this study emphasize the importance of varying
      the levels of hydrophobic and hydrophilic components within denture adhesive
      formulations, alongside the types of water present within the adhesive systems.
      This phenomenon has shown the potential to fine-tune the adhesive properties and
      failure mode against poly(methyl methacrylate), surfaces. (c) 2018 Wiley
      Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1355-1362, 2018.

PMID- 29330942
TI  - Skeletal development in the heterocercal caudal fin of spotted gar (lepisosteus
      oculatus) and other lepisosteiformes.
AB  - BACKGROUND: The caudal fin of actinopterygians experienced substantial
      morphological changes during evolution. In basal actinopterygians, the caudal fin
      skeleton supports an asymmetrical heterocercal caudal fin, while most teleosts
      have a symmetrical homocercal caudal fin. The transition from the ancestral
      heterocercal form to the derived homocercal caudal fin remains poorly understood.
      Few developmental studies provide an understanding of derived and ancestral
      characters among basal actinopterygians. To fill this gap, we examined the
      development of the caudal fin of spotted gar Lepisosteus oculatus, one of only
      eight living species of Holostei, the sister group to the teleosts. RESULTS: Our
      observations of animals from fertilization to more than a year old provide the
      most detailed description of the development of caudal fin skeletal elements in
      any Holostean species. We observed two different types of distal caudal radials
      replacing two transient plates of connective tissue, identifying two hypaxial
      ensembles separated by a space between hypurals 2 and 3. These features have not
      been described in any gar species, but can be observed in other gar species, and
      thus represent anatomical structures common to lepisosteiformes. CONCLUSIONS: The
      present work highlights the power and importance of ontogenic studies and
      provides bases for future evolutionary and morphological investigations on
      actinopterygians fins. Developmental Dynamics 247:724-740, 2018. (c) 2018 Wiley
      Periodicals, Inc.

PMID- 29330943
TI  - Epigenetic markers in circulating cell-free DNA as prognostic markers for
      survival of castration-resistant prostate cancer patients.
AB  - BACKGROUND: Noninvasive biomarkers to guide personalized treatment for castration
      resistant prostate cancer (CRPC) are needed. In this study, we analyzed
      hypermethylation patterns of two genes (GSTP1 and APC) in plasma cell-free DNA
      (cfDNA) of CRPC patients. The aim of this study was to analyze the cfDNA
      concentrations and levels of the epigenetic markers and to assess the value of
      these biomarkers for prognosis. METHODS: In this prospective study, patients were
      included before starting new treatment after developing CRPC. The blood samples
      were collected prior to start of the treatment and at three time points
      thereafter. cfDNA was extracted from 1.5 mL of plasma and before performing a
      methylation-specific PCR, bisulfate modification was carried out. RESULTS: The
      median levels of cfDNA, GSTP1, and APC copies in the baseline samples of CRPC
      patients (n = 47) were higher than in controls (n = 30). In the survival
      analysis, the group with baseline marker levels below median had significant less
      PCa-related deaths (P-values <0.02) and did not reach the median survival point.
      The survival distributions for the groups were statistically significant for the
      cfDNA concentration, GSTP1 and APC copies, as well as PSA combined with GSTP1 +
      APC (P-values <0.03). Furthermore, there were strong positive correlations
      between PSA and marker response after starting treatment (P-values <0.04).
      CONCLUSIONS: In conclusion, this study showed the kinetics of methylated cfDNA
      (GSTP1 and APC) in plasma of CRPC patients after starting treatment. Furthermore,
      the value of the markers before treatment is prognostic for overall survival.
      These results are promising for developing a test to guide treatment-decision
      making for CRPC patients.

PMID- 29330944
TI  - Improvement of islet function and survival by integration of perfluorodecalin
      into microcapsules in vivo and in vitro.
AB  - Hypoxic injury of islets is a major obstacle for encapsulated islet
      transplantation into the peritoneal cavity. To improve oxygen delivery to
      encapsulated islets, we integrated 20% of the oxygen carrier material,
      perfluorodecalin (PFD), in alginate capsules mixed with islets (PFD-alginate).
      Integration of PFD clearly improved islet viability and decreased reactive oxygen
      species production compared to islets encapsulated with alginate only (alginate)
      and naked islets exposed to hypoxia in vitro. In PFD-alginate capsules, HIF
      1alpha expression was minimal, and insulin expression was well maintained.
      Furthermore, the best islet function represented by glucose-stimulated insulin
      secretion was observed for the PFD-alginate capsules in hypoxic condition. For
      the in vivo study, the same number of naked islets and encapsulated islets
      (alginate and PFD-alginate) was transplanted into streptozotocin-induced diabetic
      mice. Nonfasting blood glucose levels and the area under the curve for glucose
      based on intraperitoneal glucose tolerance tests in the PFD-alginate group were
      lower than in the alginate group. The harvested islets stained positive for
      insulin in all groups, but the ratio of dead cell area was 4 times higher in the
      alginate group than in the PFD-alginate group. In conclusion, integration of PFD
      in alginate microcapsules improved islet function and survival by minimizing the
      hypoxic damage of islets after intraperitoneal transplantation.

PMID- 29330945
TI  - Cyclosporine A induces endothelin-converting enzyme-1: Studies in vivo and in
      vitro.
AB  - AIM: Cyclosporine A (CsA) induces renal vasoconstriction and hypoxia and enhances
      the expression of endothelin-1 (ET-1) pro-hormone (pre-pro-ET-1), plausibly
      leading to a feed-forward loop of renal vasoconstriction, hypoxia and enhanced
      synthesis of the potent vasoconstrictor ET-1. Endothelin-converting enzyme (ECE)
      1 cleaves big endothelin to generate endothelin (ET)-1 and is upregulated by
      hypoxia via hypoxia-inducible factor (HIF). We hypothesized that in addition to
      the direct induction of ET-1 synthesis, CsA might also intensify renal ECE-1
      expression, thus contributing to enhanced ET-1 synthesis following CsA. METHODS:
      CsA was administered to Sprague Dawley rats (120 mg/kg/SC) for 4 days, and renal
      HIF and ECE-1 expression were assessed with Western blots and immunostaining.
      Human umbilical vein endothelial cells (HUVEC) and proximal tubular cell line (HK
      2) were subjected to CsA, and ECE-1 induction was evaluated using real-time mRNA
      PCR and Western blots. RESULTS: Cyclosporine A intensified renal parenchymal ECE
      1 expression in the rat kidney, particularly in distal nephron segments, along
      with renal hypoxia (detected by pimonidazole adducts) and HIF expression, in line
      with our recent observations showing episodic hypoxia in mice subjected to CsA.
      Furthermore, in cultured normoxic HUVEC and HK-2 cells, CsA dose-dependently
      induced both pre-pro-ET-1 and ECE-1 mRNA and protein expression, with enhanced ET
      1 generation. CONCLUSION: CsA induces ECE-1 via both hypoxic and non-hypoxic
      pathways. ECE-1 may contribute to increased renal ET-1 generation following CsA,
      participating in a feed-forward loop of renal parenchymal hypoxia and ET
      synthesis.

PMID- 29330946
TI  - Skull Size and Biomechanics are Good Estimators of In Vivo Bite Force in Murid
      Rodents.
AB  - Rodentia is a species-rich group with diversified modes of life and diets.
      Although rodent skull morphology has been the focus of a voluminous literature,
      the functional significance of its variations has yet to be explored in live
      animals. Myomorphous rodents, including murids, have been suggested to represent
      "high-performance generalists." We measured in vivo bite force in 14 species of
      wild and lab-reared murid rodents of various sizes and diets to investigate
      potential morphofunctional differences between them. We dissected their skulls
      and computed a biomechanical model to estimate bite force. We first tested if our
      model allowed good estimation of in vivo data. Then, using morphological, in vivo
      and estimated bite force data in a phylogenetic context, we aimed to find the
      drivers of bite force differences among species. Estimated and in vivo bite
      forces were strongly correlated, which indicates that (a) biomechanical models
      allow a good estimation of real performance, and that (b) size and muscular
      changes (increased mass, fiber length, and PCSA) are the main drivers of bite
      performance differences. Myomorphous rodents, therefore, may have evolved high
      bite force through a combination of changes in size and musculature, which gave
      them a great versatility in their ability to process food. We found mixed results
      at the intraspecific level, with only some species displaying a good fit between
      estimated and in vivo measurements. We suggest that limited variation in size and
      muscular organization, and increased behavioral variation might decrease the
      precision of bite force estimates within species. Anat Rec, 301:256-266, 2018.
      (c) 2018 Wiley Periodicals, Inc.

PMID- 29330947
TI  - Dietary Correlates of Primate Masticatory Muscle Fiber Architecture.
AB  - Analyses of masticatory muscle architecture-specifically fascicle length (FL; a
      correlate of muscle stretch and contraction speed) and physiological cross
      sectional area (PCSA; a correlate of force)-reveal soft-tissue dietary
      adaptations. For instance, consumers of large, soft foods are expected to have
      relatively long FL, while consumers of obdurate foods are expected to have
      relatively high PCSA. Unfortunately, only a few studies have analyzed these
      variables across large primate samples-an order of particular interest because it
      is our own. Previous studies found that, in strepsirrhines, force variables (PCSA
      and muscle masses; MM) scale with isometry or slight positive allometry, while
      the body size corrected FL residuals correlate with food sizes. However, a study
      of platyrrhines using different methods (in which the authors physically cut
      muscles between fascicles) found very different trends: negative allometry for
      both the stretch and force variables. Here, we apply the methods used in the
      strepsirrhine study (chemical dissection of fascicles to ensure full length
      measurements) to reevaluate these trends in platyrrhines and extend this research
      to include catarrhines. Our results conform to the previous strepsirrhine trends:
      there is no evidence of negative allometry in platyrrhines. Rather, in primates
      broadly and catarrhines specifically, MM and PCSA scale with isometry or positive
      allometry. When examining size-adjusted variables, it is clear that fascicle
      lengths (especially those of the temporalis muscle) correlate with diet: species
      that consume soft, larger, foods have longer masticatory fiber lengths which
      would allow them to open their jaws to wider gape angles. Anat Rec, 301:311-324,
      2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 29330948
TI  - Inferring the Diets of Extinct Giant Lemurs from Osteological Correlates of
      Muscle Dimensions.
AB  - The jaw adductor muscles of extinct mammals are often reconstructed to elucidate
      paleoecological relationships and to make broad comparisons among taxa. Muscle
      lever arms, bite load arms, muscle dimensions, and gape are often also
      reconstructed to better understand feeding. Several different approaches to these
      and related goals are discussed here. A protocol for reconstructing muscle
      dimensions and bite force using biomechanically informative skull measurements
      and osteological proxies of muscle dimensions is described and applied to a case
      study of subfossil Malagasy lemurs. The results of this case study show that most
      subfossil lemurs emphasized the masseter and medial pterygoid muscles over the
      temporalis. This supports the inference that these extinct lemurs depended
      heavily on tough food like leaves. Exceptions include signals of hard-object
      feeding in Archaeolemur that vary between A. majori and A. edwardsi.
      Reconstructions of soft-tissue and function are important for understanding past
      ecological relationships. Even those based on well-supported osteological proxies
      from extant analogues have limitations for making precise inferences. Anat Rec,
      301:343-362, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 29330949
TI  - Functional Morphology of Mimetic Musculature in Primates: How Social Variables
      and Body Size Stack up to Phylogeny.
AB  - Mammalian skeletal muscle is influenced by the functional demands placed upon it.
      Functional morphology of facial expression musculature, or mimetic musculature,
      is largely unknown. Recently, primate mimetic musculature has been shown to
      respond to demands associated with social factors. Body size has also been
      demonstrated to affect many aspects of primate functional morphology and
      evolutionary morphology. The present study was designed to further examine the
      role of social variables and body size in influencing the morphology of primate
      mimetic musculature using a broad phylogenetic range of primates, primates with
      varying body sizes, and those that exploit differing time of day activity cycles
      and social group sizes. Gross data on mimetic musculature morphology were
      gathered from tarsiers (Tarsius bancanus), slender lorises (Loris tardigradus),
      ring-tailed lemurs (Lemur catta), crowned lemurs (Eulemur coronatus), black
      lemurs (E. macaco), owl monkeys (Aotus trivirgatus), and howler monkeys (Alouatta
      caraya) and compared to previous results from chimpanzees (Pan troglodytes),
      gibbons and siamangs (hylobatids), rhesus macaques (Macaca mulatta), Sulawesi
      macaques (M. nigra), common marmosets (Callithrix jacchus), and greater
      bushbabies (Otolemur spp.). Mimetic muscle presence/absence was observed and
      recorded. Results revealed that phylogenetic position determines the overall
      mimetic muscle groundplan, with anthropoids having a high number of muscles in
      the superciliary and midface regions, strepsirrhines having a high number of
      muscles in the external ear region, and tarsiers displaying an intermediate
      condition. Within these broad taxonomic categories body size had an effect on
      mimetic musculature, while time of day activity and social group size had smaller
      effects. Anat Rec, 301:202-215, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 29330950
TI  - Comparative Anatomy of Bat Jaw Musculature via Diffusible Iodine-Based Contrast
      Enhanced Computed Tomography.
AB  - Noctilionoid bats exhibit an extraordinary array of cranial specializations that
      match diverse diets, including variation in jaw musculature physiological cross
      sectional areas (PCSA), lever arms, and relative contribution to bite force.
      Although previous research in this group has linked variation in skull shape and
      muscle mechanics to biting performance, there are still important gaps about the
      anatomical underpinnings of noctilionoid dietary adaptations, including the
      degree of compartmentalization of the jaw musculature, and whether and how muscle
      attachment sites have evolved across noctilionoid species that specialize on
      derived diets. Here, we paired dissections with Diffusible Iodine-based Contrast
      Enhanced Computed Tomography (diceCT) scanning in a comparative anatomical study
      of the jaw musculature of 12 noctilionoid species that span all diets found
      within the clade. We evaluated changes in jaw muscle attachments across species,
      identified differences in muscle compartments, examined scaling relationships,
      and compared the power of diceCT and dissections to generate morphological data.
      We found that diceCT enables more detailed investigation of muscle compartments
      and generates greater PCSA values, but these are strongly correlated with
      estimates from dissections. Jaw muscle origin and insertion sites are relatively
      conserved across noctilionoids when compared to other species-rich and
      ecologically-diverse mammalian groups. However, we found interspecific
      differences in the degree of separation of the m. masseter, and in the scaling
      relationships of different jaw muscles with body mass, both of which might be
      associated with diet and feeding behavior specialization. Our study highlights an
      unexplored diversity in the compartmentalization and fiber architecture of bat
      jaw muscles. Anat Rec, 301:267-278, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 29330952
TI  - Jaw-Muscle Fiber Architecture and Leverage in the Hard-Object Feeding Sooty
      Mangabey are not Structured to Facilitate Relatively Large Bite Forces Compared
      to Other Papionins.
AB  - Numerous studies have sought to link craniofacial morphology with behavioral
      ecology in primates. Extant hard-object feeders have been of particular interest
      because of their potential to inform our understanding about the diets of early
      fossil hominins. Sooty mangabeys (Cercocebus atys) are hard-object feeders that
      frequently generate what have been described as audibly powerful bites at wide
      jaw gapes to process materially stiff and hard seeds. We address the hypothesis
      that sooty mangabeys have features of the masticatory apparatus that facilitate
      this feeding behavior by comparing fiber architecture and leverage of the
      masseter and temporalis muscles between sooty mangabeys and three papionin
      primates that do not specialize on hard objects. Contrary to predictions, sooty
      mangabeys do not have relatively larger muscle physiologic cross-sectional areas
      or weights compared to other papionins, nor do they consistently display improved
      leverage. In this regard, sooty mangabeys differ in their morphology from other
      hard-object feeders such as tufted capuchins. However, males of all four papionin
      species converge on a shared pattern of relatively longer anterior superficial
      masseter fibers compared with female conspecifics, suggesting that males are
      likely prioritizing muscle stretch to improve gape performance as part of a
      behavioral repertoire that includes agonistic social interactions and intense
      male-male competition. These findings strengthen support for the hypothesis that
      gape display behaviors can exert a strong selective influence throughout the
      musculoskeletal masticatory apparatus. Results also raise questions about the
      morphological suitability of extant cercopithecines as models for interpreting
      feeding behavior and diet in fossil hominins with limited jaw gape capacity. Anat
      Rec, 301:325-342, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 29330953
TI  - Jaw-Dropping: Functional Variation in the Digastric Muscle in Bats.
AB  - Diet and feeding behavior in mammals is strongly linked to the morphology of
      their feeding apparatus. Cranio-muscular morphology determines how wide,
      forcefully, and quickly the jaw can be opened or closed, which limits the size
      and material properties of the foods that a mammal can eat. Most studies of
      feeding performance in mammals have focused on skull form and jaw muscles
      involved in generating bite force, but few explore how jaw abduction is related
      to feeding performance. In this study, we explored how the morphology of the
      digastric muscle, the primary jaw abducting muscle in mammals, and its jaw lever
      mechanics are related to diet in morphologically diverse noctilionoid bats.
      Results showed that insectivorous bats have strong digastric muscles associated
      with proportionally long jaws, which suggests these species can open their jaws
      quickly and powerfully during prey capture and chewing. Short snouted frugivorous
      bats exhibit traits that would enable them to open their jaws proportionally
      wider to accommodate the large fruits that they commonly feed on. Our results
      support the hypothesis that digastric muscle and jaw morphology are correlated
      with diet in bats, and that our results may also apply to other groups of
      mammals. Anat Rec, 301:279-290, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 29330954
TI  - Why Muscles Look and Act the Way They Do: Uncovering the Nexus Among Form,
      Function, Behavior, and Evolution.

PMID- 29330955
TI  - Intrinsic Constraints on the Diversification of Neotropical Cichlid Adductor
      Mandibulae Size.
AB  - The diversification of functional traits may be constrained by intrinsic factors,
      such as structural, mechanical, developmental, or physiological limitations. We
      explored the biomechanical and constructional constraints on the size of the
      major jaw closing muscles, the adductor mandibulae complex (AM), in a diverse
      clade of freshwater fish - the Neotropical cichlids. Using phylogenetic
      comparative methods, we contrasted patterns of size variation and diversification
      rates of three AM divisions with variables describing head size and biomechanical
      coefficients describing force and velocity transmission. We found that all three
      AM muscles examined were impacted by constructional constraints, namely, (1) the
      space available in the head (head length and width-all AMs), (2) competition with
      the eye (AM1 and AM2), (3) competition for space among the three major AM
      divisions (e.g., AM1 vs. AM3), and (4) potentially the shape of the lower jaw
      (AM2). Only AM2 size was significantly associated with lower jaw biomechanical
      coefficients, but opposite predictions based on force transmission (i.e., no
      compensation for low mechanical advantage). Diversification rates of the mass of
      the divisions of the AM were also not connected to the diversification rates of
      their biomechanical coefficients. Previously suggested compensation in AM mass
      for reduced force transmission among ram-feeding predators appears to be driven
      by overall body plan changes (lengthening of the head in elongate bodies) and
      only indirectly to biomechanical trade-offs. Strong constructional constraints on
      AM size likely limit potentially functional morphospace occupation, and highlight
      the highly integrated nature of ram-suction feeding functional adaptations in
      Neotropical cichlids. Anat Rec, 301:216-226, 2018. (c) 2018 Wiley Periodicals,
      Inc.

PMID- 29330956
TI  - Craniomandibular Variation in Phalangeriform Marsupials: Functional Comparisons
      with Primates.
AB  - Phalangeriform marsupials have often been compared with primates because of
      similarity in the range of external morphology, ecological niches, and body size
      between the two radiations. We explore morphological convergence in the
      masticatory anatomy of strepsirrhine primates and phalangeriforms, through
      osteological measurements of the mandible and facial skeleton, and through
      dissection of the masticatory musculature, presenting new data on the arrangement
      and proportions of jaw adductors in phalangeriforms. Phalangeriforms and primates
      have a large number of shape differences in mandibular morphology. Despite these
      differences in shape on phylogenetic lines, dietary groups used to pool species
      of phalangeriforms and strepsirrhines also differed from each other in a range of
      shape variables. Notably, the striped possum (Dactylopsila), previously described
      as convergent with the aye-aye (Daubentonia), shares a number of features of
      mandibular shape with Daubentonia, and the exudate-feeding sugar-glider,
      Petaurus, shares shape features with gummivorous strepsirrhines. Petaurus also
      has long-fibered jaw adductors for its body mass, as would be expected for a
      species with a requirement for large gape. Phalangeriform species on the
      frugivore-folivore continuum were less clearly comparable to strepsirrhine
      species with similar diets. There are a number of significant dietary contrasts
      in osteological measurements, but in the masticatory muscles phalangeriforms did
      not meet all expectations based on available dietary data, highlighting the
      possible complexity of dietary adaptation in phalangeriform folivores. Anat Rec,
      301:227-255, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 29330951
TI  - Dynamic Musculoskeletal Functional Morphology: Integrating diceCT and XROMM.
AB  - The tradeoff between force and velocity in skeletal muscle is a fundamental
      constraint on vertebrate musculoskeletal design (form:function relationships).
      Understanding how and why different lineages address this biomechanical problem
      is an important goal of vertebrate musculoskeletal functional morphology. Our
      ability to answer questions about the different solutions to this tradeoff has
      been significantly improved by recent advances in techniques for quantifying
      musculoskeletal morphology and movement. Herein, we have three objectives: (1)
      review the morphological and physiological parameters that affect muscle function
      and how these parameters interact; (2) discuss the necessity of integrating
      morphological and physiological lines of evidence to understand muscle function
      and the new, high resolution imaging technologies that do so; and (3) present a
      method that integrates high spatiotemporal resolution motion capture (XROMM,
      including its corollary fluoromicrometry), high resolution soft tissue imaging
      (diceCT), and electromyography to study musculoskeletal dynamics in vivo. The
      method is demonstrated using a case study of in vivo primate hyolingual
      biomechanics during chewing and swallowing. A sensitivity analysis demonstrates
      that small deviations in reconstructed hyoid muscle attachment site location
      introduce an average error of 13.2% to in vivo muscle kinematics. The observed
      hyoid and muscle kinematics suggest that hyoid elevation is produced by multiple
      muscles and that fascicle rotation and tendon strain decouple fascicle strain
      from hyoid movement and whole muscle length. Lastly, we highlight current
      limitations of these techniques, some of which will likely soon be overcome
      through methodological improvements, and some of which are inherent. Anat Rec,
      301:378-406, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 29330957
TI  - Behavioral Correlates of Cranial Muscle Functional Morphology.
AB  - This issue of the Anatomical Record is the first of a two-volume set that focuses
      on new investigations into behavioral correlates of muscle functional morphology.
      Much of the research on functional morphology and adaptation to specific
      functional niches focuses on the shapes of hard-tissues-bones and teeth.
      Investigations into soft-tissue anatomy tend to be predominantly descriptive with
      only brief allusion to ontogenetic or evolutionary origins of structures. When
      muscles are included in analyses of functional systems, their function tends to
      be oversimplified-usually considered a simple force vector connecting two
      osteological points, with the force treated as a constant derived from some
      simple calculation of muscle size. The goal of these special issues is to present
      a series of studies that take a more elaborate look at how muscles can be viewed
      from a functional perspective in studies searching for morphological correlates
      of behavior. This first volume focuses on the behavioral correlates of cranial
      muscles-starting with a paper about the mimetic musculature of primates and
      ending with a series of papers on the masticatory muscles of many lineages of
      vertebrates. The next issue of the Anatomical Record (March 2018) includes our
      papers on the behavioral correlates of postcranial muscles. Taken together, we
      hope you agree that this series presents valuable insights into these
      form/function relationships using both traditional approaches+ and cutting-edge
      techniques. Anat Rec, 301:197-201, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 29330958
TI  - Do Muscles Constrain Skull Shape Evolution in Strepsirrhines?
AB  - Despite great interest and decades of research, the musculoskeletal relationships
      of the masticatory system in primates are still not fully understood. However,
      without a clear understanding of the interplay between muscles and bones it
      remains difficult to understand the functional significance of morphological
      traits of the skeleton. Here, we aim to study the impacts of the masticatory
      muscles on the shape of the cranium and the mandible as well as their co
      variation in strepsirrhine primates. To do so, we use 3D geometric morphometric
      approaches to assess the shape of each bone of the skull of 20 species for which
      muscle data are available in the literature. Impacts of the masticatory muscles
      on the skull shape were assessed using non-phylogenetic regressions and
      phylogenetic regressions whereas co-variations were assessed using two-blocks
      partial least square (2B-PLS) and phylogenetic 2B-PLS. Our results show that
      there is a phylogenetic signal for skull shape and masticatory muscles. They also
      show that there is a significant impact of the masticatory muscles on cranial
      shape but not as much as on the mandible. The co-variations are also stronger
      between the masticatory muscles and cranial shape even when taking into account
      phylogeny. Interestingly, the results of co-variation between the masticatory
      muscles and mandibular shape show a more complex pattern in two different
      directions to get strong muscles associated with mandibular shape: a folivore way
      (with the bamboo lemurs and sifakas) and a hard-object eater one (with the aye
      aye). Anat Rec, 301:291-310, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 29330959
TI  - Non-Destructive Determination of Muscle Architectural Variables Through the Use
      of DiceCT.
AB  - The fascicular architecture of skeletal muscle dictates functional parameters
      such as force production and contractile velocity. Muscle microarchitecture is
      typically determined by means of manual dissection, a technique that is
      inherently destructive to specimens. Furthermore, fascicle lengths and pennation
      angles are commonly assessed at only a limited number of sampling sites per
      muscle. We present the results of a digital technique to non-destructively assess
      muscle architectural variables for three jaw-adductor muscles within a specimen
      of the cercopithecine primate Macaca fascicularis (crab-eating macaque). The
      specimen is first subjected to a contrast-enhanced staining protocol to increase
      the density of internal soft tissues. High-resolution uCT scans are then
      collected and segmented to isolate individual muscles. A textural orientation
      algorithm is then applied to each muscle volume to reconstruct constituent muscle
      fascicles in three dimensions. Using this technique, we report muscle volume,
      fascicle length, angle of pennation, and physiological cross-sectional area
      (PCSA) for each muscle. These data are compared to results collected using
      traditional dissection of the contralateral muscles. Reconstructions of muscle
      volume and pennation angle closely correspond to the dissection results. The
      degree of similarity between measurements of fascicle length and PCSA varies
      between muscles, with temporalis demonstrating the greatest disparity between
      techniques; likely reflecting the complex geometry and fascicular arrangement of
      this muscle. The described technique samples a much larger number of fascicles
      than had previously been possible and non-destructively investigates the internal
      architecture of preserved specimens. We conclude that this approach demonstrates
      great potential for quantifying muscle internal architecture. Anat Rec, 301:363
      377, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 29330960
TI  - The Anatomical Record Flexes Its Muscle With a Special Issue Examining Behavioral
      Adaptations in Muscle Functional Morphology.

PMID- 29330961
TI  - Clinical value of 4-hour delayed gadolinium-Enhanced 3D FLAIR MR Images in Acute
      Vestibular Neuritis.
AB  - OBJECTIVE: To investigate the clinical significance of 4-hour delayed-enhanced
      3.0 Tesla three-dimensional (3D) fluid-attenuated inversion recovery (FLAIR)
      magnetic resonance (MR) imaging in acute vestibular neuritis. STUDY DESIGN: A
      prospective observational study. METHODS: Twenty-nine vestibular neuritis
      patients were enrolled between January 2017 and June 2017. Vestibular function
      tests, comprising the caloric and video head impulse tests and vestibular-evoked
      myogenic potential measurements, were performed. Precontrast, 10-minute, and 4
      hour delayed-enhanced 3D-FLAIR MR images using double-dose IV gadolinium were
      obtained. After laterality and extent of inner ear enhancement were defined, the
      patients were divided into groups based on the patterns of enhancement, and
      clinical parameters were analyzed according to the groups. RESULTS: Twenty
      patients (20 of 29, 69.0%) had obviously asymmetric enhancement of the affected
      inner ear structures on 4-hour delayed images, whereas only three patients
      (10.3%) had marked enhancement on 10-minute delayed images. The duration of
      spontaneous nystagmus (DurSN) was significantly longer in the patients with
      enhancement, especially with enhancement of the whole inner ear, including the
      vestibule and semicircular canals (P < 0.033). Spontaneous nystagmus resolved
      within 12 days in patients without laterality of enhancement, and within 16 days
      in ipsilesional enhancement confined to the inner auditory canal and fundus.
      Other results of vestibular function tests did not reveal any significant
      associations with MR enhancement. CONCLUSIONS: Contrast enhancement of the
      vestibular nerve and inner ear structures can be identified on 4-hour delayed
      enhanced 3T 3D-FLAIR MR images in acute vestibular neuritis. The extent of inner
      ear enhancement may be associated with the DurSN. LEVEL OF EVIDENCE: 4.
      Laryngoscope, 1946-1951, 2018.

PMID- 29330962
TI  - Skin Conformal Polymer Electrodes for Clinical ECG and EEG Recordings.
AB  - Preparation-free and skin compliant biopotential electrodes with high recording
      quality enable wearables for future healthcare and the Internet of Humans. Here,
      super-soft and self-adhesive electrodes are presented for use on dry and hairy
      skin without skin preparation or attachment pressure. The electrodes show a skin
      contact impedance of 50 kOmega cm2 at 10 Hz that is comparable to clinical
      standard gel electrodes and lower than existing dry electrodes. Microstructured
      electrodes inspired by grasshopper feet adhere repeatedly to the skin with a
      force of up to 0.1 N cm-2 without further attachment even during strong movement
      or deformation of the skin. Skin compliance and adhesive properties of the
      electrodes result in reduction of noise and motion artifacts superior to other
      dry electrodes reaching the performance of commercial gel electrodes. The signal
      quality is demonstrated by recording a high-fidelity electrocardiograms of a
      swimmer in water. Furthermore, an electrode with soft macropillars is used to
      detect alpha activity in the electroencephalograms from the back of the head
      through dense hair. Compared to gel electrodes, the soft biopotential electrodes
      are nearly imperceptible to the wearer and cause no skin irritations even after
      hours of application. The electrodes presented here could combine unobtrusive and
      long-term biopotential recordings with clinical-grade signal performance.

PMID- 29330963
TI  - Metal-organic framework based in-syringe solid-phase extraction for the on-site
      sampling of polycyclic aromatic hydrocarbons from environmental water samples.
AB  - In-syringe solid-phase extraction is a promising sample pretreatment method for
      the on-site sampling of water samples because of its outstanding advantages of
      portability, simple operation, short extraction time, and low cost. In this work,
      a novel in-syringe solid-phase extraction device using metal-organic frameworks
      as the adsorbent was fabricated for the on-site sampling of polycyclic aromatic
      hydrocarbons from environmental waters. Trace polycyclic aromatic hydrocarbons
      were effectively extracted through the self-made device followed by gas
      chromatography with mass spectrometry analysis. Owing to the excellent adsorption
      performance of metal-organic frameworks, the analytes could be completely
      adsorbed during one adsorption cycle, thus effectively shortening the extraction
      time. Moreover, the adsorbed analytes could remain stable on the device for at
      least 7 days, revealing the potential of the self-made device for on-site
      sampling of degradable compounds in remote regions. The limit of detection ranged
      from 0.20 to 1.9 ng/L under the optimum conditions. Satisfactory recoveries
      varying from 84.4 to 104.5% and relative standard deviations below 9.7% were
      obtained in real samples analysis. The results of this study promote the
      application of metal-organic frameworks in sample preparation and demonstrate the
      great potential of in-syringe solid-phase extraction for the on-site sampling of
      trace contaminants in environmental waters.

PMID- 29330964
TI  - Spectrum of bone marrow pathology and hematological abnormalities in
      methylmalonic acidemia.
AB  - Patients with isolated methylmalonic acidemia (MMA) may present with a wide range
      of hematological complications including anemia, leukopenia, thrombocytopenia,
      and pancytopenia. However, there are very limited data on the development of
      hemophagocytosis or myelodysplasia in these patients. We report three patients
      with isolated MUT related MMA who presented with severe refractory pancytopenia
      during acute illness. Their bone marrow examination revealed a wide spectrum of
      pathology varying from bone marrow hypoplasia, hemophagocytosis to myelodysplasia
      with ring sideroblasts. We discuss their management and outcome. This report
      emphasizes the need for bone marrow examination in these patients with refractory
      or unexplained severe cytopenia, to confirm bone marrow pathology, and to rule
      out other diseases with similar clinical presentation for a better clinical
      outcome.

PMID- 29330965
TI  - Intrahepatic bile duct primary cilia in biliary atresia.
AB  - AIM: The etiopathogenesis of non-syndromic biliary atresia (BA) is obscure. The
      primary aim was to investigate intrahepatic bile duct cilia (IHBC) in BA at
      diagnosis and its correlation with clinical outcome. The secondary aim was to
      analyze IHBC in routine paraffin-embedded liver biopsies using conventional
      scanning electron microscopy (SEM). METHODS: Surgical liver biopsies taken at
      diagnosis from 22 BA infants (age range, 39-116 days) and from eight children
      with non-BA chronic cholestasis (age range, 162 days -16.8 years) were evaluated
      for IHBC by immunofluorescence (IF) and SEM. A minimum 18-month follow-up after
      surgery was available for all patients. RESULTS: By IF, cilia were present in 6/8
      (75%) non-BA but only in 3/22 (14%) BA cases, and cilia were reduced or absent in
      19/22 (86%) BA and 2/8 (25%) non-BA livers (P < 0.01). In BA, cilia presence was
      found to be associated with clearance of jaundice at 6-month follow-up (P <
      0.05). However, high overall survival rates with native liver, >90% at 12 months,
      and >70% at 24 months post-surgery, were recorded regardless of cilia
      presence/absence at diagnosis. Electron microscopy was able to detect bile ducts
      and cilia in routine liver biopsies, revealing significant abnormalities in 100%
      BA livers. CONCLUSIONS: The presence of IHBC in BA livers at the diagnosis was
      associated with resolution of cholestasis, although was not predictive of short
      term survival with native liver. Scanning electron microscopy represents a
      powerful new tool to study routine liver biopsies in biliary disorders. Cilia
      dysfunction in BA pathogenesis and/or disease progression warrants further
      investigation.

PMID- 29330966
TI  - Static hyperinflation is associated with ventilatory limitation and exercise
      tolerance in adult cystic fibrosis.
AB  - INTRODUCTION: Lung hyperinflation is a potential mechanism limiting exercise
      tolerance. However, available data on the impact of static hyperinflation on
      exercise performance in adult cystic fibrosis are lacking. Furthermore, the
      relative contribution of both static and dynamic hyperinflation to exercise
      performance is unknown. OBJECTIVES: The aim of this study was to determine the
      impact of static hyperinflation on exercise tolerance and lung dynamics in adult
      cystic fibrosis. METHODS: Clinical data of 107 adult patients with cystic
      fibrosis, including pulmonary function, lung volumes and cardiopulmonary exercise
      from the Toronto Cystic Fibrosis database, were collected and analyzed. Patients
      were classified as having static hyperinflation with a residual volume to total
      lung capacity (RV/TLC) ratio of 30% or greater. RESULTS: Patients with static
      hyperinflation demonstrated a significant reduction in exercise performance [peak
      oxygen uptake (% predicted) 70 +/- 17 vs 80 +/- 17; P = .006] and were more
      likely to experience ventilatory limitation when exercising (Fisher's exact test
      P < .001). Correlation analysis showed significant relationships between measures
      of static hyperinflation [RV/TLC ratio (%)] and exercise performance [peak oxygen
      uptake (% predicted); r = -.38, P < .001] and dynamic hyperinflation (r = -.35, P
      < .001). Multiple linear regression showed that the contribution of static
      hyperinflation to exercise performance [peak oxygen uptake (% predicted)] was
      greater than that of airway obstruction (forced expiratory volume in 1 second).
      CONCLUSION: Clinicians working with this patient group in a pulmonary
      rehabilitation or health care setting may wish to consider using measures of
      static hyperinflation as end points to determine program or treatment efficacy.

PMID- 29330968
TI  - Correlation of dynamic contrast-enhanced MRI derived volume transfer constant
      with histological angiogenic markers in high-grade gliomas.
AB  - INTRODUCTION: To ascertain if the volume transfer constant (Ktrans ) derived from
      T1 dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) correlates with
      the immunohistological markers of angiogenesis in high-grade gliomas. METHODS:
      Fifty-one image-guided biopsy specimens in 34 patients with newly presenting high
      grade gliomas (grade III = 16; grade IV = 18) underwent preoperative imaging
      (conventional imaging and T1 DCE-MRI). We correlated vascular endothelial growth
      factor (VEGF) expression and the microvessel density (MVD) of MRI-guided biopsy
      specimens with the corresponding DCE-derived Ktrans . Histological sections were
      stained with VEGF and CD34, and examined under light microscopy. These
      histological and molecular markers of angiogenesis were correlated with the
      Ktrans of the region of interest corresponding to the biopsy specimen. RESULTS:
      The Ktrans showed a significant positive correlation with VEGF expression (rho =
      0.582, P = 0.001) but not with MVD stained with CD34 antibody (rho = 0.328, P =
      0.072). CONCLUSION: The Ktrans derived from DCE-MRI can reflect the VEGF
      expression of high-grade gliomas but not the MVD.

PMID- 29330967
TI  - The impact of bisphenol S on bovine granulosa and theca cells.
AB  - Bisphenol S (BPS) is an endocrine-disrupting chemical with multiple potential
      mechanisms of action, including as an oestrogen receptor agonist. BPS is
      increasingly used in plastics and thermal receipts as a substitute for bisphenol
      A, which has been phased out due to concerns about human health implications. The
      ability of BPS to alter female reproductive function in mammals has not been
      widely studied, despite the importance of normal hormone signalling for female
      reproduction. The aim of this study was to investigate how BPS (in a wide range
      of doses, including very low doses) affects granulosa cell and theca cell steroid
      hormone production and cell viability in the bovine. Granulosa cell oestradiol
      production was stimulated when cells were exposed to 100 MUM BPS under basal
      conditions, but there was no effect of BPS when cells were stimulated with
      follicle-stimulating hormone (FSH). Additionally, there was no effect of BPS on
      granulosa cell progesterone production or cell viability under basal or FSH
      stimulated conditions. BPS did not affect theca cell androstenedione or
      progesterone production, or theca cell viability under basal or luteinizing
      hormone-stimulated conditions. This study suggests for the first time that BPS
      may alter oestradiol production by bovine granulosa cells, albeit at a
      concentration that is unlikely to be physiologically relevant. Further studies
      are needed to determine the effects of BPS on the bovine oocyte and on other
      functions of follicular cells.

PMID- 29330969
TI  - Is salinity an obstacle for biological invasions?
AB  - Invasions of freshwater habitats by marine and brackish species have become more
      frequent in recent years with many of those species originating from the Ponto
      Caspian region. Populations of Ponto-Caspian species have successfully
      established in the North and Baltic Seas and their adjoining rivers, as well as
      in the Great Lakes-St. Lawrence River region. To determine if Ponto-Caspian taxa
      more readily acclimatize to and colonize diverse salinity habitats than taxa from
      other regions, we conducted laboratory experiments on 22 populations of eight
      gammarid species native to the Ponto-Caspian, Northern European and Great Lakes
      St. Lawrence River regions. In addition, we conducted a literature search to
      survey salinity ranges of these species worldwide. Finally, to explore
      evolutionary relationships among examined species and their populations, we
      sequenced the mitochondrial cytochrome c oxidase subunit I gene (COI) from
      individuals used for our experiments. Our study revealed that all tested
      populations tolerate wide ranges of salinity, however, different patterns arose
      among species from different regions. Ponto-Caspian taxa showed lower mortality
      in fresh water, while Northern European taxa showed lower mortality in fully
      marine conditions. Genetic analyses showed evolutionary divergence among species
      from different regions. Due to the geological history of the two regions, as well
      as high tolerance of Ponto-Caspian species to fresh water, whereas Northern
      European species are more tolerant of fully marine conditions, we suggest that
      species originating from the Ponto-Caspian and Northern European regions may be
      adapted to freshwater and marine environments, respectively. Consequently, the
      perception that Ponto-Caspian species are more successful colonizers might be
      biased by the fact that areas with highest introduction frequency of NIS (i.e.,
      shipping ports) are environmentally variable habitats which often include
      freshwater conditions that cannot be tolerated by euryhaline taxa of marine
      origin.

PMID- 29330971
TI  - Pakistan's March Towards Universal Health Coverage.

PMID- 29330970
TI  - Gamma-glutamyl transferase activity as a predictive marker for severity of
      obstructive sleep apnea syndrome and concomitant hypertension.
AB  - BACKGROUND: Chronic intermittent hypia, inflammation and oxidative stress are
      involved in resultant obstructive sleep apnea syndrome (OSAS), which may affect
      numerous regulatory mechanisms that play a role in the regulation of blood
      pressure. Gamma-glutamyl transferase (GGT) is a novel marker in the prediction of
      cardiovascular risk. OBJECTIVE: The objective of this study was to investigate
      the correlation of serum levels of GGT with hypertension and the degree of the
      upper airway obstruction in subjects with OSAS. METHODS: A total of 270 subjects
      that met the inclusion criteria were enrolled in the study. The subjects were
      divided into four separate groups according to the apnea-hypopnea index (AHI)
      scores as the control group (AHI < 5), mild OSAS group (AHI 5-15), moderate OSAS
      group (AHI 16-30) and severe OSAS group (AHI >30). A further classification of
      the OSAS subjects was made in two groups based on the presence of hypertension.
      RESULTS: The study included 43 control individuals and 59 subjects with mild, 54
      subjects with moderate and 114 subjects with severe OSAS. The serum levels of GGT
      were found to be significantly correlated with OSAS severity (control group: 18
      +/- 3.3, mild OSAS: 23.6 +/- 7.3, moderate OSAS: 26.4 +/- 7.5 and severe OSAS:
      39.8 +/- 12). Serum levels of GGT were found to be significantly higher in OSAS
      subjects with concomitant hypertension than in the group without associated
      hypertension (P < .05). The results showed that the adjusted mean GGT under OSA
      without hypertension (Madj  = 28.76, SE = 0.71) was significantly lower than in
      cases with OSA with hypertension (Madj  = 42.79, SE = 1.19). CONCLUSION: The
      present study indicated a strong correlation between high serum levels of GGT and
      concomitant hypertension in subjects with obstructive sleep apnea. This biomarker
      may be helpful in grading the severity of obstructive sleep apnea and correlated
      with hypertension in this population.

PMID- 29330972
TI  - Immunohistochemical Evaluation Of Oestrogen Receptors In Adenoid Cystic Carcinoma
      Of Salivary Gland.
AB  - Background: Oestrogen has a physiological role throughout the body including oral
      cavity. The effects are mediated by binding to two receptors in nucleus alpha and
      beta, which are ligand-activated transcription factors. The alpha receptors have
      a prognostic significance in cancer of breast while in Adenoid cystic carcinoma
      of salivary glands the results are inconsistent. This study was conducted to
      determine the oestrogen receptor Alpha staining in adenoid cystic carcinoma of
      salivary gland. Methods: Paraffin blocks of thirty cases of adenoid cystic
      carcinoma of salivary gland were retrieved and evaluated through
      immunohistochemistry by anti-oestrogen antibody clone 1D5.The intensity and
      proportion of nuclear staining was scored using Allred scoring system. Results:
      From total of thirty cases, 5 cases expressed as mild staining of oestrogen
      receptors using Allred scoring system. Three cases of cribriform and two cases
      from tubular pattern expressed positivity. In the case series selection of our
      study cohort there was no association seen in age, gender, site and histological
      type of tumour with the expression of oestrogen receptor. Conclusions: Role of
      oestrogen is well established in breast cancers, some of salivary gland adenoid
      cystic carcinoma also express these receptors and could be involved in the
      pathogenesis. Further studies are recommended to seek possible explanation of
      variable staining pattern observed in many other studies, and also to determine
      the possible therapeutic use of tamoxifen in such tumours.

PMID- 29330973
TI  - The Effect Of Sex Education And Life Skills For Preventive Sexual Risk Behaviours
      Among University Of Students In Thailand.
AB  - BACKGROUND: Currently, the problem of sexual risk behaviour of adolescents has
      increased worldwide, including Thailand. This study compared the effectiveness of
      promoting life skills to prevent sexual risk behaviours among university students
      in the Phayao Province of Thailand. METHODS: A quasi-experimental design was
      employed with a pre- and post-test study for a sample of freshmen university
      students. The students were then split into an intervention group comprised of
      300 students, with a second group of 250 students from the same faculty as the
      control group. The intervention group participated in the integrated life skills
      model for preventing sexual risk behaviours and participatory learning. The
      educational activities included; lectures, brainstorming, group discussion,
      roleplaying, game simulations and naming experiences through six weekly life
      skills training sessions of 90 minutes each. Data were collected by self
      questionnaires and analysed using descriptive statistics and independent sample t
      testing. Three different time periods were examined using ANOVA repeated measures
      analysis of variance. RESULTS: Compared between the intervention and control
      groups determined that implementation of increased knowledge and improved life
      skills was statistically significant (p<0.001) in the intervention group. The
      intervention group also showed significantly improved communication skills and
      behavioural preventive measures towards sexual risk than the control group
      (p<0.001). CONCLUSIONS: The life skills model also effectively reduced the sexual
      risk behaviours of students at the university. Therefore, this program was
      beneficial for the development of strategies to increase self-efficacy and it
      should be integrated into the universities' curriculum. In the long-term sexual
      risk behaviour changes must be monitored for programme sustainability.

PMID- 29330974
TI  - Nucleic Acid Amplification Test For Detection Of West Nile Virus Infection In
      Pakistani Blood Donors.
AB  - BACKGROUND: The study was planned to determine the presence of West Nile Virus
      (WNV) infection in Pakistani blood donors, using Nucleic Acid Amplification Test
      (NAT). METHODS: The blood donors for study were selected on the basis of the
      standard questionnaire and routine screening results. Six donors were pooled
      using an automated pipettor and NAT for WNV was performed on Roche Cobas s 201
      NAT system. The reactive pools were resolved in Individual Donation-NAT (ID-NAT)
      format and a sample from FFP bags of reactive donations was retrieved. NAT was
      again performed on retrieved plasma bag (RPB) sample to confirm the reactive
      donations. The donors were also recalled and interviewed about history of illness
      related to recent WNV infection. RESULTS: After serological screening of 1929
      donors during the study period, 1860 donors were selected for NAT test for WNV
      detection. The mean age of the donors was 28+/-8.77 (range: 18-57 years). 1847
      (99.3%) donors were male and 13 (0.7%) were female. NAT for WNV identified six
      initially reactive pools (0.32%). On follow-up testing with RPB samples, 4 donors
      (0.21%) were found confirmed reactive for WNV RNA (NAT yield of 1 in 465 blood
      donors). CONCLUSIONS: WNV is a threat to safety of blood products in Pakistan. A
      screening strategy can be implemented after a large-scale study and financial
      considerations. One of the reduced cost screening strategies is seasonal
      screening of blood donors for WNV, with pooling of samples.

PMID- 29330975
TI  - Emergency Inguinal Hernia Repair: Comparison Of Desarda's Versus Darning
      Technique.
AB  - BACKGROUND: Emergency inguinal hernia repair remains the commonest operation
      performed by general surgeons all over the world. The aim of this study was to
      compare the mean operative time, post-operative pain, wound infection and early
      recurrence between Desarda's and Darning emergency inguinal hernia repair.
      METHODS: This is a randomized controlled trial conducted at Jinnah Postgraduate
      Medical Centre, Karachi. A total of 186 patients of male gender between ages 20
      60 years with incarcerated, obstructed and strangulated inguinal hernia were
      enrolled in the study. Patients with primary and recurrent inguinal hernias were
      excluded. All patients were randomized to Desarda group (n=93) and Darning group
      (n=93). RESULTS: Mean operative time in Desarda group was 55.53+/-6.81 minutes
      and mean operative time in darning group was 53.06+/-5.51 minutes (p-value
      0.007). Mild to moderate pain was found insignificantly higher in Desarda group
      75 (80.6%) as compared to Darning group 66 (71%) (p-value 0.170). Wound infection
      was found higher in Desarda group 18 (19.4%) as compared to darning group 9
      (9.7%) (p-value 0.061). Recurrence was found significantly higher 15 (55.5%) in
      Darning group as compared to Desarda group 2 (7.4%) (p-value <0.001).
      CONCLUSIONS: No significant difference was observed in the postoperative pain,
      wound infection however, significant differences were observed in the mean
      operative time and recurrence rates.

PMID- 29330976
TI  - Ranitidine Can Potentiate The Prokinetic Effect Of Itopride At Low Doses- An In
      Vitro Study.
AB  - BACKGROUND: Gastroparesis and GERD occur concomitantly in 40 percent of the
      cases. Prokinetic drugs and acid blockers are employed as the main treatment
      modality. Ranitidine is an acid blocker with additional prokinetic activity and
      Itopride is a known prokinetic drug. This study was designed to observe the
      synergistic potentiating prokinetic effect of Ranitidine on itopride on isolated
      duodenum of rabbits. METHODS: Ranitidine (10-5-10-3) and itopride (10-6-10-5)
      were added in increasing concentrations to isolated duodenum of rabbits and
      contractions were recorded on PowerLab Data acquisition unit AHK/214. Cumulative
      dose response curves were constructed. The potentiating prokinetic effect of
      Ranitidine on itopride was seen by using a fixed dose of ranitidine and
      cumulatively enhancing doses of itopride on iWorx. RESULTS: Ranitidine and
      itopride produced a dose dependent reversible contraction of the isolated tissue
      of rabbits with ranitidine showing a max response of 0.124mV and itopride showing
      a maximum response of 0.131mV. Ranitidine was able to potentiate the prokinetic
      effect of itopride at low doses but at high dose the effect began to wane off.
      CONCLUSIONS: Ranitidine and itopride produce a statistically significant
      synergistic potentiating prokinetic effect at low doses in vitro.

PMID- 29330977
TI  - Effectiveness Of Horizontal Peer-Assisted Learning In Physical Examination
      Performance.
AB  - BACKGROUND: All students cannot be individually trained in physical examination
      skills due to faculty and time limitations. Peer-assisted learning (PAL) can
      solve this dilemma if it is used in undergraduate curriculum. Empirical
      effectiveness of horizontal peer-assisted learning model has not been reported
      previously. The objective of this study was to compare horizontal peer-assisted
      learning (PAL) with expert-assisted learning (EAL) in teaching of physical
      examination skills. METHODS: This is a randomized controlled study (Solomon four
      group design) carried out at a medical school. A total of 120 undergraduate year
      5 students were randomized into two groups to undergo training in four areas of
      physical examination. Stratified random sampling technique was used. Group 1 was
      trained by EAL while Group 2 by PAL. Half students from both groups were given a
      pre-test to assess the testing effect. Both groups were given a post-test in the
      form of an OSCE. Independent samples t-test and paired sample t-test were used as
      tests of significance. RESULTS: Group 2 scored significantly higher than Group 1.
      There was significant difference (p=.000) in mean post-test scores of Group-1
      (69.98+/-5.6) and Group-2 (85.27+/-5.6). Difference in mean scores was not
      significant (p=.977) between students who had taken the pre-test and those who
      had not. CONCLUSIONS: This study has implications in curriculum development as it
      provides quantitative evidence indicating that horizontal PAL as a learning
      strategy can actually replace, rather than augment, expert-assisted learning in
      teaching clinical skills to undergraduate students.

PMID- 29330978
TI  - Intramuscular Diclofenac Vs Periprostatic Lidocaine Injection For Controlling
      Pain Undergoing Transrectal Ultrasound Guided Prostatic Biopsy.
AB  - BACKGROUND: Transrectal ultrasound (TRUS) technique for getting prostatic tissue
      for histopathology is now the standard procedure for malignant lesions of the
      prostate and imperative diagnostic investigation of patients with clinical specks
      of prostatic neoplasia. During TRUS guided biopsy, pain control has been
      important issue therefore, highly potent analgesia before this procedure should
      be considered on high priority according to current census. Therefore, we
      compared intramuscular diclofenac injection with sensory blockade of injection
      lidocaine to abolish pain undergoing prostatic biopsy with TRUS technique.
      METHODS: Total 200 patients were selected for this study having raised PSA values
      and suspicious nodule on Digital Rectal Examination. These patients were
      segregated into two groups by randomization. Group "A" received intramuscular
      diclofenac and group "B" were infiltrated with lidocaine injection for sensory
      blockade. RESULTS: Patients in group A was having mean age of 64.5+/-5.8 years
      while for group B patients was 65.6+/-4.9 years (p=0.16). Both groups have
      statistically insignificant difference in their mean PSA values (p=0.24) and mean
      prostatic volume (p=0.22). The mean pain scores on visual analogue scale in
      groups A was 3.5+/-0.8 and in group B it was 2.4+/-0.8 (p<0.001). 60% group A
      patients reported with mild or no pain compared to 90% in group B. (p<0.001)..
      CONCLUSIONS: Local blockade with lidocaine injection has better pain control as
      compared to patients experienced pain with intramuscular diclofenac used for
      prostatic biopsy through TRUS technique..

PMID- 29330979
TI  - Early Versus Delayed Laparoscopic Cholecystectomy For Acute Cholecystitis.
AB  - BACKGROUND: Laparoscopic cholecystectomy is considered the gold standard for the
      management of acute cholecystitis but controversy surrounds the timings of the
      surgery. Studies are available favouring both early and delayed laparoscopic
      cholecystectomy. The objective of this study was to compare early versus delayed
      laparoscopic cholecystectomy for acute cholecystitis. METHODS: This quasi
      experimental study included 180 patients irrespective of their age and sex
      presented at department of Surgery, Lahore General Hospital between January to
      December 2014 with a diagnosis of acute cholecystitis were assigned randomly to
      early laparoscopic cholecystectomy within 24 h of admission or to initial
      conservative treatment followed by delayed laparoscopic cholecystectomy, 6-12
      weeks later. RESULTS: The mean operating time was 64.32 min vs. 58.24 min in the
      delayed group, conversion rate (early 15.5% vs. delayed 14.4%). The mean
      postoperative hospital stay was 1.67 days in the earlier group and 4.38 days in
      the delayed group. Overall mortality was zero. CONCLUSIONS: Early laparoscopic
      cholecystectomy for acute cholecystitis is safe, offering economic benefit of
      much shorter hospital stay and quick recovery.

PMID- 29330980
TI  - Comparison Of Efficacy Of Chloroquine And Artemether/Lumafantrine In Treating
      Vivax Malaria In Thall And Surrounding Area.
AB  - BACKGROUND: Fever is the main complaint in patients reporting to our hospital and
      the most common cause of fever in our set up is malaria. The aim of this study
      was to know about the clinical response, efficacy and resistance of vivax malaria
      to chloroquine in patients reporting to Thall Scouts Hospital. METHODS: All the
      adult male patients reporting to Thall Scouts Hospital with fever and other
      symptoms of malaria having slide positive vivax malaria were included in the
      study. Both thick and thin slide were used for the diagnosis and species
      determination of malaria. Age group of the patients was from 18-40 years old. The
      study was conducted for the period of two years. RESULTS: Total number of
      patients included in the study was 518. Of the 518 patients, 374 (72.2%)
      responded to chloroquine and the remaining 144 (27.8%) were given
      Arthemether/Lumafantrine combination. Having positive symptoms of malaria total
      374 patients treated with chloroquine 171 (45.72%) were asymptomatic after 24
      hours, 98 (26.2%) after 48 hours, 78 (20.86%), after 72 hours of treatment while
      27 (7.22%) were found to be resistant to chloroquine. Of the 144 patients having
      positive malaria treated with Artemether/Lumafantrine 62 (43.06%) were
      asymptomatic after 24 hours, 65 (45.14%) after 48 hours, 13 (9.03%) after 72
      hours while 4 (2.78%) had still positive symptoms of malaria. CONCLUSIONS: Vivax
      malaria in our set up is sensitive to both Chloroquine and
      Arthemether/Lumafantrine. As Chloroquine is a cheap and easily available drug, so
      it can be safely given to patients with vivax malaria. It will also decrease the
      total cost of the disease.

PMID- 29330981
TI  - Comparison Of Ziehl-Neelsen Based Light Microscopy With Led Fluorescent
      Microscopy For Tuberculosis Diagnosis: An Insight From A Limited Resource-High
      Burden setting.
AB  - BACKGROUND: Microscopy is the most widely used tool for Tuberculosis screening.
      Conventionally, Ziehl-Neelsen (ZN) staining has been the widely used for staining
      Acid-Fast Bacilli (AFB) but with the advent of Fluorescent staining, Auramine O
      stain is now being adapted as the preferred method for setups with high workload
      as it has the advantage of being less laborious, since bacteria fluoresce in
      front of a dark background and are easier to count. This study was performed to
      compare the efficiency of the two methods in a high-burden, limited resource
      setting to see the magnitude of diagnostic accuracy between ZN and Fluorescent
      Microscopy, using culture as the standard.. METHODS: Altogether 987 culturally
      confirmed cases were considered from the period 36 months during January 2011 to
      December 2013 and data were compiled from the records maintained at the
      Provincial Tuberculosis Reference Laboratory at Ojha Institute of Chest Diseases,
      Dow University of Health Sciences, Karachi. The results from 523 cases examined
      using ZN and 464 cases using Fluorescent staining method were compared for
      diagnostic accuracy on the basis of Mycobacterial culture results. Smears are
      prepared from the clinical samples obtained from presumptive tuberculosis
      patients. RESULTS: The results of ZN method showed 94.23% [95% CI 91.32-96.39%]
      sensitivity and 84.91% [95% CI 78.38-90.08%] specificity. While FM showed a
      sensitivity of 97.15% [95% CI 94.82-98.63%] and specificity of 83.19% [95% CI
      74.99-89.56%].. CONCLUSIONS: The results showed that Fluorescent microscopy was
      slightly more sensitive than ZN light Microscopy, while specificity of both the
      methods were comparable.

PMID- 29330982
TI  - Assessment Of Safety Levels In Operation Rooms At Two Major Tertiary Care Public
      Hospitals Of Karachi. "Safe Surgery Saves Life".
AB  - BACKGROUND: The objectives of this study are to determine the knowledge and
      attitude towards surgical safety among the health care professionals including
      surgeons, anaesthetist, hospital administrators, and operation room personnel and
      raise awareness towards the importance of safe surgery. METHODS: A pilot cross-
      sectional study of 543 healthcare providers working in the operating rooms and
      the surgical intensive care units was conducted in two tertiary care hospitals,
      within a study period of one month. A structured questionnaire was constructed
      and an informed verbal consent was taken. The questionnaire was then distributed;
      data collected and analysed on SPSS 20.0.. RESULTS: A total of 543 respondents
      participated in the study out of which there were 375 (69%) men and 168 (31%)
      women. The ages ranged between 23-58 years, mean 40.5+/-24.74. There were110
      (20.25%) surgeons, 58 (10.68%) anaesthetist, 132 (24.30%) trainees, 125 (23.02%)
      technicians, and were 118 (21.73%) nurses. The question regarding briefing
      operation room personnel is important for patient safety was agreed by 532 (98%)
      respondents. Amongst the respondents, 239 (44%) did not feel safe to be operated
      in their own setup. Team communication improvement through the check list
      implementation was agreed by 483 (89%) respondents. 514 (94.7%) opted for the
      checklist to be used while they are being operated. That operation room personnel
      frequently disregard established protocols was agreed by 374 (69%) respondents.
      193 (35.54%) of the respondents stated that it is difficult for them to speak up
      in the OR if they perceive a problem with patient care. CONCLUSIONS: Operation
      room personnel were not aware of several important areas related to briefing,
      communication, safety attitude, following standard protocols and use of WHO
      Surgical Safety check list. A pre-post intervention study should be conducted
      after formal introduction of the Checklist. Successful implementation will
      require taking all stake holders on board and rigorous training workshops,
      reinforcing and revisiting.

PMID- 29330983
TI  - Ultrasound And Supine Chest Radiograph In Road Traffic Accident Patients: A
      Reliable And Convenient Way To Diagnose Pleural Effusion.
AB  - BACKGROUND: Portable bed side ultrasound and supine chest radiograph of 80
      traumatic patients excluding very clinically unstable patients who subsequently
      underwent CT scan chest was done for traumatic effusion showing that ultrasound
      had a higher sensitivity than CXR, 88.23% and 77.94%, respectively, and a similar
      specificity of 100% and 100%, respectively. Objective of the study is to compare
      the diagnostic accuracy of high resolution ultrasound and supine chest x-ray in
      detection of pleural effusion in road traffic accident patients keeping plain CT
      chest as gold standard. METHODS: This study was conducted in PIMS and PAEC
      General Hospital, Islamabad from 1st January to 15th December 2015. The current
      study examined total of 80 trauma (blunt and penetrating) patients coming to
      emergency departments of both hospitals specifically those who had road traffic
      accident history. Their portable bed side ultrasound and supine chest radiograph
      were performed for assessing pleural effusion and subsequently CT scan chest was
      done for confirmation as it's a gold standard. RESULTS: Using CT findings as gold
      standard the sensitivity, specificity, positive predictive value and negative
      predictive value was assessed for both ultrasonography and chest radiography and
      found to be 88.23%,100%, 100%, 40% and 77.94%, 100%, 100%, 55.55% respectively
      with diagnostic accuracy of ultrasound 90% as compared to 81.25% for supine chest
      x-rays when compared with gold standard. CONCLUSIONS: Ultrasound and chest x-ray
      can be used as a useful and suitable adjunct to CT in road traffic accident
      patients as these are easily available, non-invasive, no contrast required, can
      be performed on bed side and carries no or little radiation risk.

PMID- 29330984
TI  - Polydioxanone Versus Polypropylene Closure For Midline Abdominal Incisions.
AB  - BACKGROUND: Midline laparotomy is the most common technique of abdominal
      incisions because it is simple, provides adequate exposure to all four quadrants,
      and is rapid to open. A major problem after midline laparotomy remains the
      adequate technique of abdominal fascia closure. This study was conducted to see
      the role of Polydioxanone and Prolene for midline abdominal closure in terms of
      postoperative wound infection and wound pain. METHODS: This study was carried out
      at surgical unit II, Federal Government Services Hospital Islamabad. Patients
      were equally divided in two groups, i.e., A and B. Groups A and B patients
      undergone midline abdominal closure with Polydioxanone number 1 and Polypropylene
      number 1 sutures respectively. RESULTS: Total 620 patients were included in this
      study. Post-operative wound pain score according to Visual analogue scale (VAS)
      was compared in terms of no pain (0), mild pain (1-3), moderate pain (4-6),
      severe pain (7-9). In group A (Polydioxanone), the frequency and percentages of
      no, mild, moderate and severe pain were 101 (32.6%), 95 (30.6%), 81 (26.1%) and
      33 (10.6%) respectively, where as in group B (polypropylene) it was 82 (26.5%),
      43 (13.9%), 59 (19%) and 126 (40.6%) respectively. Similarly, the frequency and
      percentages of post-operative wound infection in group A (Polydioxanone) and
      group B (polypropylene) was 105 (33.9%) and 208 (67.1%) respectively.
      CONCLUSIONS: Polydioxanone results in less wound pain and wound infection when
      compared to Polypropylene.

PMID- 29330985
TI  - Medical Students' Perceptions Of Their Learning Environment At Lahore Medical And
      Dental College Lahore.
AB  - BACKGROUND: The present study was designed to assess medical students'
      perceptions of their learning environment at Lahore Medical and Dental College,
      Lahore. METHODS: It was a crosssectional descriptive study conducted at Lahore
      Medical and Dental College, Lahore. Five hundred and thirty-three students
      participated in this study. A questionnaire was used as a study tool, comprising
      of demographic information and the 'Dundee Ready Education Environment Measure'
      (DREEM) inventory. Data was entered and analyzed using SPSS 21 package. A
      comparison of scores between different MBBS classes was done by using ANOVA.
      Comparison of scores between gender and high school education was done by using
      Mann-Whitney U tests. RESULTS: Study population included 62% females and 32%
      males. About 58% of the participants were between 18-21 years and 42% were
      between 22-25 years of age. The mean total DREEM score was 120.27/200. The mean
      score of the domains: 'Students' perceptions of learning' was 28.31/48,
      'Students' perceptions of teaching' was 26.92/44, 'Students' academic self-
      perceptions' was 21.37/32, 'Students' perceptions of atmosphere' was 27.72/48,
      and 'Students' social selfperceptions' was 16.40/28. Total DREEM and its
      subclasses score was significantly higher in F. Sc. students than the students
      with A level/American board (p-value <0.001). When DREEM scores were analyzed
      according to gender, perceptions of both male and female were positive. Age had
      no significant bearing on the total DREEM scores or scores in its subclasses.
      CONCLUSIONS: Overall perceptions or experiences of the MBBS students of their
      learning environment at Lahore medical and Dental College, Lahore were more
      positive.

PMID- 29330986
TI  - Use Of Psychoactive Drugs Among Medical Undergraduates In Abbottabad.
AB  - BACKGROUND: Psychoactive substance abuse is prevalent among medical
      undergraduates of Pakistan, India & Western countries which can adversely affect
      the physical & psychological grooming of a medical undergraduate thus threatening
      to compromise their role as future physicians & health-care providers in the
      society. The objective of the present cross-sectional study was to explore the
      prevalence and patterns of psychoactive substance/drug consumption among
      undergraduate students of a public sector medical college in Abbottabad. METHODS:
      Seven hundred and eighty participants after informed consent were requested to
      fill a questionnaire seeking information about their demographics, patterns &
      behaviours regarding ten common psychoactive substances of abuse including
      (Cigarettes, Benzodiazepines, naswar, cannabis, alcohol, amphetamine, opium,
      cocaine, heroin & organic solvents). RESULTS: Overall students who responded were
      698 (89.48%). One hundred and fifty (21.49%) admitted to the use of a
      psychoactive substance in past or at present. Majority users (71.33%) were males.
      Overall (81.33%) users were living in hostel or a rented apartment. Substance
      abuse was more prevalent among senior students, i.e., 30.06% & 24.24% in 4th year
      & final year MBBS respectively. Majority of the consumers, i.e., 93 (62%) were
      falling in an age group between 15-20 years. Main reasons behind substance abuse
      were: psychological stress (49.33%) and pleasure seeking (42.67%).
      Substances/drugs used by students in order of preference were Cigarettes 115
      (76.67%), Benzodiazepines 48 (32%), naswar 42 (28%), Cannabis 41 (27.33%),
      Alcohol 24 (16%), Amphetamine 22 (14.67%), Opium 15 (10%), Cocaine 14 (9.33%),
      Heroin 11 (7.33%) & Organic solvents 05 (3.33%). Use of more than one substance
      was observed in 70 (46.67%) students. CONCLUSIONS: It is concluded that
      prevalence of cigarette smoking, naswar, benzodiazepines, cannabis & alcohol is
      high among medical undergraduates in Abbottabad which is a matter of concern.
      Efforts are needed to create better awareness among them about the hazards of
      substance abuse on their health, upcoming professional career and ailing humanity
      under their care.

PMID- 29330987
TI  - Pattern Of Dyslipidaemia And Its Association With Hypovitaminosis D In Type 2
      Diabetes Mellitus.
AB  - BACKGROUND: Macrovascular atherosclerosis is an important long-term complication
      of type 2 diabetes mellitus. Concurrent dyslipidaemia acts as an additional risk
      factor for these complications. Hypovitaminosis D has been associated with
      adverse cardiovascular events. These modifiable risk factors of cardiovascular
      disease are inter-related. In the presence of an increasing incidence of type 2
      diabetes mellitus and its associated metabolic abnormalities and widespread
      vitamin D deficiency in Pakistan, this association needs to be investigated. The
      purpose of our study was to determine the pattern of dyslipidaemia and its
      association with low vitamin D levels in South Asian diabetics. METHODS: The
      study was designed as a quantitative cross-sectional study. It was conducted at
      the Department of Medicine, Sir Syed College of Medical Sciences and Hospital,
      Karachi from January to June 2014. A total of 168 adult consecutive patients with
      type 2 diabetes mellitus of both the genders were included. Data was collected
      and analysed using SPSS-20.0. The association of dyslipidaemia with vitamin D
      status was computed through Chi-square test. RESULTS: We found that dyslipidaemia
      is highly prevalent in patients with type 2 diabetes mellitus in Pakistan. High
      total cholesterol, LDL cholesterol and triglycerides show significant association
      with vitamin D deficiency. CONCLUSIONS: In order to decrease the development of
      diabetic complications aggressive management of hyperglycaemia and dyslipidaemia
      is required. Vitamin D supplementation may play a dual role in these situations.

PMID- 29330988
TI  - Microbiological Profile From Middle Ear And Nasopharynx In Patients Suffering
      From Chronic Active Mucosal Otitis Media.
AB  - BACKGROUND: Chronic otitis media is described as a tympanic membrane perforation
      and ear discharge for more than six weeks duration. Ascending infection from the
      nasopharynx into the middle ear cleft has been attributed to prevent resolution
      of chronic otitis media. This research aims to determine the association between
      the microbiological flora of the nasopharynx with that of the middle ear in
      patients suffering from chronic (active) mucosal otitis media.. METHODS: Our
      study is a hospital-based cross-sectional survey. It was conducted from December
      2015 to February 2017 at the Department of ENT, Combined Military Hospital,
      Abbottabad. Ear and nasopharyngeal swabs were obtained from 65 patients of
      chronic active mucosal otitis media and sent for microbiological analysis.
      Microbiological culture and sensitivity test was performed to identify the
      microbial spectrum of each specimen. Performa bearing the result of otoscopy,
      aspirate and swabs were completed for middle ear and the nasopharyngeal culture
      with reference to each patient. Descriptive statistics and Pearson's chi square
      analysis were performed using SPSS-22. RESULTS: Staphylococcus aureus and
      Pseudomonas aeruginosa are foremost microorganisms found in otorrhea culture
      isolated from patients of chronic active mucosal otitis media. Majority of the
      cultures from nasopharynx of these patients did not reveal any growth after
      incubation for 48 hours. CONCLUSIONS: A statistically insignificant association
      exists between the microbiological spectrum of the middle ear and the nasopharynx
      of patients suffering from chronic active mucosal otitis media. Micro organisms'
      exposure from a perforated tympanic membrane remains leading cause of persistent
      otorrhea, rather than ascending infection through the Eustachian tube.

PMID- 29330989
TI  - Hepatitis B And Hepatitis C Virus In Women With First Pregnancy.
AB  - BACKGROUND: Hepatitis B and Hepatitis C are amongst the leading causes of
      morbidity and mortality in pregnant women throughout the globe. This study is
      aimed at determining the frequency of these infections among primigravid females
      and the common factors that make them prone to these infections. METHODS: This
      cross-sectional study was conducted at Ayub Teaching Hospital, Abbottabad from
      December 2015 to May 2016. A total of 174 jaundiced primigravida patients were
      included in the study through non-probability consecutive sampling. Blood samples
      were sent for HBsAg and anti-HCV ELISA. Samples were analysed by the pathologist
      with more than 5 years clinical experience. All data will be analysed using SPSS
      16. RESULTS: The mean age of the subjects was 24+/-5.7 years. Six (3.4%) patients
      were HBsAg positive and 13 (7.5%) were anti-HCV positive. About 9% of patients
      had undergone surgery in their life and 1.7% reported having received blood
      transfusion during their life. Thirty-two of them had history of intravenous or
      intramuscular injections. History of piercing of body part mostly ear-piercing
      for ornaments was present in 170 (97.7%) respondents. However, the frequency of
      blood transfusion, surgery and body piercing was not statistically significantly
      between HBsAg positive, HBsAg negative, and anti-HCV positive and negative
      patients (p>0.05). CONCLUSIONS: The incidence of these viral infections in our
      community is on the rise. It emphasizes the need of routine antenatal screening
      in pregnant ladies for these viruses and to educate the public about preventive
      measures against these infections.

PMID- 29330990
TI  - Association Of Quality Of Sleep With Cognitive Decline Among The Patients Of
      Chronic Kidney Disease Undergoing Haemodialysis.
AB  - BACKGROUND: This study was conducted to determine the association between the
      subjective quality of sleep and cognitive decline among the patients of chronic
      kidney disease (CKD) undergoing haemodialysis. METHODS: In this cross-sectional
      study 106 patients of chronic kidney disease (CKD) undergoing haemodialysis at a
      tertiary care hospital in Rawalpindi, Pakistan were included in the final
      analysis. Cognitive decline was measured by British Columbia Cognitive Complaints
      Inventory (BC-CCI). Sleep quality was measured by using the Pittsburgh Sleep
      Quality Index (PSQI). Relationship of age, gender, marital status, education,
      occupation, BMI, duration of dialysis, dialysis count per week, family income,
      tobacco smoking and use of naswar was assessed with the cognitive decline..
      RESULTS: Out of 106 patients screened through BC-CCI and PSQI, 13.1% had no
      cognitive decline while 86.9% had significant cognitive decline. Relationship
      between quality of sleep and cognitive decline was significant on binary logistic
      regression.. CONCLUSIONS: This study showed significant relationship between the
      sleep quality and cognitive decline among the patients of CKD undergoing
      haemodialysis. The findings of our study also call for a greater degree of
      understanding of the physical and psychological state of patients of CKD
      undergoing haemodialysis.

PMID- 29330991
TI  - Diaphyseal Nutrient Foramina In Dried Human Adult Long Bones Of Lower Limb In
      Pakistan.
AB  - BACKGROUND: osteogenesis needs circulation of blood in the bones. Bone growth,
      repair of fracture, maintenance of bone vitality and other injures also need
      blood circulation in proper way. Blood is allowed to flow via holes in the
      diaphysis, which are called as nutrient foramina. METHODS: The crosssectional
      study was done in the department of Anatomy, Ayub and Khyber Medical College
      (Osteology Sections). The aim was to observe diaphyseal nutrient foramina in the
      human long bones of the lower limb. The study was done on 90 long bones of lower
      limb consisting of 30 femora, 30 tibiae and 30 fibulae. Of all these bones, sex
      was not determined. All the bones were macroscopically observed. For the number
      of the foramina, simple counting was done. The foraminae 1 mm away from the
      borders were counted. All positions were seen macroscopically. For direction and
      obliquity, stiff wire was used. RESULTS: We studied 90 long bones of lower limb.
      About 80% of long bones of lower limb showed single nutrient foramina. About 18%
      of lower limb long bones showed two nutrient foraminae. In cases of femora
      nutrient foraminae were directed proximally. In cases of fibulae and tibiae most
      of the foramina were directed distally. CONCLUSIONS: the study has provided
      additional information on the foramina index, morphology and topography of the
      nutrient foramina. In the lower limb long bones, the anatomical data is important
      for the clinicians as the micro-vascular bone transfer is becoming popular. This
      morphological data can be used by the forensic experts in identification through
      different landmarks in bones development giving an aid in medicolegal work.

PMID- 29330992
TI  - Client Satisfaction And Decision Making Amongst Females Visiting Family Planning
      Clinics In Hyderabad, Pakistan.
AB  - BACKGROUND: Family Planning is the basic right of the human being. It involves
      decision regarding the number of children and desired space between children by
      the couple themselves. Quality services involving multiple dimensions build the
      confidence of the clients and lack of quality is one of the constraints behind
      incomplete coverage of family planning. Objectives of the current study were to
      determine the client satisfaction, decision-making process and various influences
      on clients in adopting family planning methods. METHODS: This cross-sectional
      study was conducted at Family Planning Centre of Liaquat University Hospital,
      Hyderabad in 2016. Quality of the family planning services and satisfaction with
      the services were assessed through responses obtained from women selected
      purposively and visiting family planning centre through exit interviews with
      structured pretested and reliable questionnaire after taking the written consent.
      RESULTS: Access to Family Planning Centre was not an issue in 92% cases but only
      31% respondents were appropriately greeted, 77% faced blank expression and 13%
      received sufficient privacy. Health problems and socioeconomic conditions were
      inquired by 41% and18% providers respectively, while motivating force for service
      use was mother in law in most 35% cases. Health workers were successful in
      clarifying misinformation (86%) and explaining side effects (71%) but only 21%
      respondents were satisfied with services. Respondents are influenced by family
      and health care providers while making decision and type of influence was
      considered positive by 83% respondents. CONCLUSIONS: Training and monitoring
      system be strengthened at family planning centres to improve quality of services
      while important influencing relations be focused for family planning education to
      improve utilization of services.

PMID- 29330993
TI  - Chemical Composition Of Stones In Paediatric Urolithiasis.
AB  - BACKGROUND: Chemical composition of stones is one of the important diagnostic
      criteria for aetiology of stone formation and treatment to prevent recurrence.
      This paper reports composition of stones in children at a tertiary hospital by
      Fourier Transformation Infrared Spectroscopy (FTIR). METHODS: Between January
      June 2015, 412 urinary stones from children were analysed by FTIR. Chi-square
      tests were used for the comparison of categorical measurements between groups.
      All reported values were 2-sided and statistical significance was considered at p
      value <=0.05. RESULTS: Of the 412 stones, 263 (63.8%) were renal, 101(24.5%)
      bladder and 48 (11.7%) ureteric. The mean age of children was 7.15+/-4.13 years
      with a M:F ratio 2.4:1. Of the 412 stones, 144(34.9%) were pure stones composed
      of one compound and 268(65.1%) were mixtures. Frequency of compound in stones was
      Ammonium Acid Urate (AAU) (65%), Calcium Oxalate (CaOx) (76.9%), Uric Acid (5%),
      Calcium Phosphate Apatite (7%), Whitlockite (8.4%), Struvite (4%), Cystine
      (0.72%) and Xanthine (2.11%). Frequency of compounds analysed in three ages
      groups 0-5, 6-10 and 11-15 years showed high frequency of AAU (73%) in 0-5 years
      as compared to (60%) in 11-15 years (p<0.018). CaOx (90%) in 11-15 as compared to
      (62.5%) in 0-5 years (p<0.001). Bladder stones were more prevalent in children 0
      5 years (32%) vs 19% in 11-15 years (p<0.004) while renal were 75% in 11-15 years
      and 54% in 0-5 years (p<0.04). CONCLUSIONS: AAU stones known to be associated
      with malnutrition and chronic diarrhoea are highly prevalent in paediatric stones
      formers in our population in the kidney, bladder and ureter.

PMID- 29330994
TI  - Pattern Of Causative Micro-Organisms In Catheter Related Blood Stream Infections
      In Dialysis Patients: Experience From Saudi Arabia.
AB  - BACKGROUND: Catheter related blood stream infections (CRBSI) are the leading
      cause of morbidity in HD patients. The majority of these infections relate to
      haemodialysis catheters. There is a paucity of local data on microbial agents
      responsible for CRBSI in our region. This prompted our study. METHODS: This
      Prospective observatory survey was conducted in Department of Nephrology, King
      Fahd Hospital, Hofuf KSA from Nov 2014 to Jan 2017 (26 months). It was performed
      on dialysis patients with HD catheters who developed features of CRBSI. Blood
      cultures were taken from the patient and cultured microorganisms were observed
      and stratified according to type and prevalence in relation to age gender and
      comorbidities. RESULTS: There were 210 distinct episodes of CRBSI. 61.5% (n=129)
      were due to gram negative microorganisms and 38.5% (n=81) were due to Gram
      positive microorganism. Fifty-three events were due to Coagulase Negative
      Staphylococcus aureus. Enterobacter cloachae accounted for 28 events. Pseudomonas
      19 events, Enterococcus faecalis 13, Klebsiella 11, Acinitobacter accounted for 8
      events. CRBSI was observed more frequently in males (n=136), diabetics (n=113)
      and in age 40 years+/-19 years(n=97). CONCLUSIONS: Gram negative microorganisms
      were more commonly responsible for CRBSI in our settings. Enterobacter cloachae
      was most common gram-negative microorganism responsible for CRBSI, a finding not
      observed in other studies. There was significant predisposition to diabetics,
      male gender and middle age group. We need further studies to observe antibiotics
      sensitivity of microorganisms so that we can standardize empirical antibiotics in
      cases of CRBSI.

PMID- 29330995
TI  - Depression In Myocardial Infarction Patients At Ayub Teaching Hospital
      Abbottabad.
AB  - BACKGROUND: There is a considerably high prevalence of depression in post
      myocardial infarction (MI) patients. This study was designed with an aim to
      detect depression in patients with acute MI admitted to the CCU at Ayub Teaching
      Hospital Abbottabad.. METHODS: This descriptive crosssectional study enrolled 246
      male and female patients with acute MI. The patients were interviewed on the 3rd
      day of admission and their answers were marked according to the HADS-D scale.
      RESULTS: With a cut-off score of 11, the frequency of depression in study
      participants was 27.24% (n=67). No statistically significant association was
      found between the age and sex of patients and depression. CONCLUSIONS: Depression
      is fairly common following acute MI and the management plans should include a
      consultation with psychiatric for individualized management of depression in post
      myocardial infarction patients..

PMID- 29330996
TI  - Missed Immunization Opportunities Among Children Under 5 Years Of Age Dwelling In
      Karachi City.
AB  - BACKGROUND: Immunization is the safest and effective measure for preventing and
      eradicating various communicable diseases. A glaring immunization gap exists
      between developing and industrialized countries towards immunization, because the
      developing countries including Pakistan are still striving to provide basic
      immunization to their children. The purpose of this study was to access the
      prevalence and factors of missing immunization among under 5-year children of
      Karachi.. METHODS: A cross sectional study was conducted from June 2015 to
      October 2015 among different outpatient clinics of Karachi. Parents who had child
      less than 5 year of age were approached by non-probability purposive sampling.
      Data was analysed by using Statistical Package of Social Sciences. RESULTS: There
      were around 59.09% (n=156) and 64.43% (n=165) parents who have correctly
      responded regarding the number of essential immunization visit during the first
      and second year of their child life respectively. About 28.12% (n=108) parents
      responded that they do not know about the name and number of missed doses of
      vaccines. 31.78% (n=122) parents responded that their children have missed either
      one or more than one doses of routine immunization vaccines. Of which 34.42%
      (n=42) children have missed more than one vaccine. Lack of knowledge regarding
      immunization schedule 28.68% (n=34), concern about vaccine side effects 21.31%,
      (n=26), child sickness 17.21% (n=21), and lack of trust about government 10.65%,
      (n=13) were the major barriers identified by parents for missed immunization
      opportunities. CONCLUSIONS: Parents have inadequate knowledge regarding routine
      immunization visits, immunization schedule and vaccine doses. The practices of
      parents for routine childhood immunization are also poor. Parents refuse to
      immunize their child because of lack of immunization visit knowledge and also
      because of their doubts regarding vaccine potency and side effects. A proper
      system of immunization promotion, advocacy and reminder systems with proper
      follow-up mechanism need to be developed by all healthcare centres.

PMID- 29330997
TI  - Comparison Of Different Formulations Of Vitamin D.
AB  - BACKGROUND: Vitamin D Deficiency (VDD) is responsible for a wide spectrum of
      clinical diseases and vitamin D deficiency prevalence is frightening in most
      parts of the world including Pakistan. Therefore, supplementations of vitamin D
      are used in the population at high risk for the prevention and the treatment of
      vitamin D deficiency. Vitamin D supplementation comes in various formulations
      both oral and intramuscular. Cholecalciferol is the most commonly used
      preparation which is given through these routes of administration. There is need
      to study the fact that how much vitamin D levels are raised after administration
      of these different formulations as this can be a pivotal factor in determining
      dosage and route of vitamin D3. METHODS: This cross-sectional study conducted on
      320 cases and compared the efficacy of various Vitamin D3 preparations in raising
      Vitamin D levels conducted in Department of Endocrinology and Metabolism,
      Services Hospital, Lahore from February to July, 2016. Blood serum was drawn for
      vitamin D level in the cases at the time of presentation and after treatment.
      RESULTS: Three hundred & twenty patients were enrolled in study and divided into
      four groups (A, B, C, D). There was no significant difference between groups (A,
      B, C, D) in change in vitamin d levels after 3 months of treatment (p-Value
      0.446). CONCLUSIONS: Different preparations of vitamin D are equally effective in
      raising vitamin D levels at 12 weeks. However, there is a need to conduct large
      scale studies to further validate these results.

PMID- 29330998
TI  - Histomorphological Effects Of Hunger Stress On Ovaries.
AB  - BACKGROUND: Incidence of stress is on the rise in our daily life involving
      various neurobiological, endocrinological and behavioral changes. Hunger stress
      has a potent influence on mental, physical, and reproductive health by affecting
      the hypothalamic-pituitary gonadal axis. METHODS: It was a laboratory based
      randomized control trial. Adult female mice (BALB-c strain) weighing 25-27 grams
      on first day of estrous cycle were taken in two groups (ten each). Group A was
      kept in normal environment of animal house for one month. Group B was given
      hunger stress by restricting the diet to about 50% per day for one month. Right
      ovaries of the animals were dissected out and observed for shape, color, and
      weight. Histological slides were prepared for the count of primary, secondary,
      and tertiary follicles. RESULTS: Statistically significant decrease in animal and
      ovary weight with significant fall in ovarian follicles was observed.
      CONCLUSIONS: Hunger stress affects the ovaries by reducing its weight and number
      of follicles.

PMID- 29330999
TI  - Reasons Of Self-Discharge From Nursery Of A Tertiary Care Hospital.
AB  - BACKGROUND: Patients who leave against medical advice (LAMA) from a health
      facility is a recognized problem. In neonatology practice this issue is
      particularly sensitive as repercussions can be severe. The purpose of this study
      was to evaluate the factors influencing the decision of parents to self-discharge
      their babies against medical advice. METHODS: This descriptive case series was
      conducted in the Department of Neonatology, of the Children's Hospital and the
      Institute of Child Health, Lahore from January to June 2015. A total of 240
      patients who self-discharged/were included. RESULTS: There were (59.6%) males and
      (40.4%) females with a male to female ratio of 2:1.5. Term babies constituted
      (67.9%), spontaneous vaginal deliveries (59.1%) and (55.8%) were delivered at
      hospitals. Seventy seven new-borns (32.2%) had birth asphyxia followed by
      neonatal sepsis (27.9%). Sixty four (64.5%) self-discharged within first week of
      admission. More babies were signed LAMA at week end (32.1%). Likewise (53.1%)
      babies were self- discharged during the night shift. Highest rate of LAMA was
      seen in parents belonging to low socioeconomic class (72.1%). Ninety eight
      parents (40.8%) had no formal education while well-educated parents were found to
      be 35 (14.6%). The commonest reason for selfdischarge was "perceived poor
      clinical outcome" (36.7%) by parents. CONCLUSIONS: Multiple factors were
      implicated in self-discharges from neonatology unit. Commonest reasons cited by
      parents were perception of poor clinical outcome and family pressures. Other
      contributory factors were male gender; those delivered vaginally, diagnosis of
      birth asphyxia, first week of life, at weekends and night hours. Low
      socioeconomic class and education of parents was also a major causative factor.

PMID- 29331000
TI  - Evaluation Of Peer Assisted Learning In Evidence Based Medicine Course: A Pilot
      Study At University Of Glasgow.
AB  - BACKGROUND: Peer Assisted Learning (PAL) is a well-established approach in
      learning and is increasingly being utilized in the medical education system. It
      is a process where active help of peer group members is taken for learning. This
      study aimed to look at the impact of peer assisted learning on the students at
      the end of the session. METHODS: Sixteen Postgraduate students attending Evidence
      Based Medicine (EBM) course spanning over two semesters (6 months each) were
      recruited. It was a cross sectional study and non-probability convenience
      sampling technique was used for gathering data. All students enrolled in EBM
      course conducted an hour-long PAL session during the coursework. At the end of
      the semester a link to an online questionnaire was sent to all the participants.
      A set of both open and closed ended questions were included in the questionnaire.
      RESULTS: Response rate was 87.5%, 14 out of the 16 students completed the
      questionnaire. The results showed an affirmative change in the behaviour and
      attitude of the participants' after the workshops. Majority of the respondents
      were of the opinion that it was a valuable experience and they benefitted through
      involvement in the process. Most of the postgraduate students suggested that it
      should be implemented in post graduate studies especially medical education.
      CONCLUSIONS: PAL is more interactive and informal way of teaching and it helps in
      the professional development, if peers from different specialties are gathered.
      However, study with a larger sample size are suggested to prove the
      generalizability of this assertion.

PMID- 29331001
TI  - Depression And Associated Factors: A Cross-Sectional Study Using Beck Depression
      Inventory.
AB  - BACKGROUND: Mental health disorders are becoming an increasingly common
      occurrence worldwide and present a major public health concern. Depression has
      been recognized as a major contributor in mental health disability burden. This
      study aims to determine the frequency of depression among individuals presenting
      at a rural health facility in Lahore and to identify the risk factors associated
      with it.. METHODS: A cross sectional study was conducted at Rural Health Centre
      Kahna Nau, Lahore from January to April 2017. A sample of 384 consenting
      individuals presenting at the rural health facility were selected through
      consecutive sampling technique. Beck Depression Inventory (BDI), was used to
      assess the level of depression amongst the respondents. We categorized the BDI
      score for this study into BDI >=20 as "depressed" and BDI <20 as "non-depressed".
      Data was entered and analysed by using SPSS 16.0. Chi-square test was carried out
      to identify factors associated with depression, significant at a p-value of
      <=0.05. RESULTS: Out of total, 258 (69.5%) respondents were males with 197 (53%)
      in age category of 25-44 years. BDI scale showed 84 (23%) respondents to be
      suffering from depression. Age (p=0.002), income (p=0.003), marital status
      (p=0.023), educational status (0.011), family structure (p=0.041), history of
      hospitalization (p=0.003), smoking status (0.012) and co-morbidity (p=0.001) were
      significantly associated with depression. CONCLUSIONS: Our study found a
      substantial proportion of patients' who were suffering from depression. Age,
      income, marital status, educational qualification, family structure, co-morbidity
      and smoking status were significantly associated with depression.

PMID- 29331002
TI  - Genetics Of Human Hereditary Hearing Impairment.
AB  - Hereditary hearing impairment is heterogeneous type of disorder which can be
      caused due to environmental as well as genetical factors. Two distinct types of
      hereditary hearing loss are syndromic or non-syndromic. Non-syndromic hearing
      loss is further categorized as autosomal recessive, autosomal dominant, X-linked
      and mitochondrial deafness. Autosomal recessive occurs more frequently as
      compared to autosomal dominant. Mutations in various genes are responsible for
      hereditary hearing impairment. To date, about 99 autosomal recessives and 67
      autosomal dominant genes for deafness have been discovered. Some of important
      genes include GJB2, JGB6, GJB3 which encodes gap junction proteins, MYO7A, MYO15A
      encodes myosine proteins, OTOF encodes otoferlin, and SLC26A4 encodes anion
      exchanger protein. Up till now, the mutation in GJB2 gene occurs more frequently
      in different population of the world and cause autosomal recessive hearing
      impairment. The purpose of this review article was to explore the mutation and
      function of those muted genes which encode different type of protein and
      responsible either for autosomal recessive or autosomal dominant hearing
      impairment.

PMID- 29331003
TI  - Oral Sildenafil Use In Neonates With Persistent Pulmonary Hypertension Of
      Newborn.
AB  - BACKGROUND: The prevalence of PPHN has been estimated at 1.9 per 1000 live
      births. After the discovery of iNO's, its efficacy and benefit in PPHN is well
      established. Even in the best of centers equipped with iNo and ECMO the mortality
      is around 20%. Also, iNO is expensive and difficult to administer and monitor
      which makes it difficult choice in our part of the world. Furthermore About 40%
      of patients do not respond or have rebound pulmonary hypertension after
      discontinuation. Owing to these reasons, other treatment modalities like
      phosphodiesterase inhibitors such as Sildenafil need to be evaluated. METHODS: We
      report a retrospective case series of eighteen patients with PPHN admitted in
      NICU and treated with oral sildenafil. RESULTS: Three (17%) babies had mild, 5
      (28%) moderate and 10 (55%) severe PPHN based on echocardiography. Sildenafil was
      started on all patients on a mean of 1.67 days and stopped on mean 12.6 days.
      Initial fio2 was 100%, which after starting sildenafil decreased gradually to 40%
      on mean 10 days. Average length of stay in NICU was 13 days. Twelve (67%)
      patients survived whereas 6 (33%) expired (Figure 2). No improvement in oxygen
      Index after 36 hours (p<0.05) was the independent predicting risk factor for PPHN
      related mortality in the expired patients. CONCLUSIONS: Oral sildenafil can be a
      used in conjunction with other treatment modalities for PPHN especially in
      resource limited settings. However further studies regarding its comparative
      efficacy need to be done.

PMID- 29331004
TI  - Cholecystectomy For Gall Stones In 26 Months Old Child.
AB  - Cholelithiasis is a major cause of morbidity worldwide. The incidence of gall
      stone in children in Pakistan has not been sufficiently studied and is
      increasingly being detected: the reason may be a true rise in the incidence or an
      improvement in diagnosis due to liberal use of diagnostic facilities and thus the
      increased opportunity to detect disease. A healthy 2 years and 2 months old male
      child presented to outpatient with history of recurrent attacks of pain abdomen
      and anorexia. Ultrasonography showed a 0.6 mm stone, inflammation and
      pericholecystic fluid. Open cholecystectomy was performed under general
      anaesthesia. A distended gall bladder with multiple very small calculi was
      removed. Post-operative stay was uneventful and patient was allowed oral feeds
      after 24 hours.

PMID- 29331005
TI  - Pregnant Lady With Undiagnosed Hodgkin's Disease Presenting As Secondary
      Sclerosing Cholangitis.
AB  - Hodgkin's lymphoma. A 25 years old lady, 34 weeks primigravida was referred from
      the Emergency Department to the Medical Unit Khyber Teaching Hospital-MTI,
      Peshawar with four weeks of fever, progressive jaundice, pruritus, night sweats
      and weight loss. LFTs showed cholestatic picture, ERCP showed scanty intrahepatic
      giving beading and autumn tree appearance typical of sclerosing cholangitis. CBD
      was normal. Doppler U/S of hepatic and portal vein reported normal. She was
      started on steroids, ursodeoxycholic acid and antibiotics 3rd generation
      cephalosporins to which she did not respond well. This prompted a Liver biopsy
      which showed Hodgkin's disease having mixed cellularity. She was shifted to
      specialized oncology unit for further management where she died of irreversible
      liver damage. This is a rare case of secondary sclerosing cholangitis in
      Hodgkin's lymphoma of liver and the first case reported to our Hospital.

PMID- 29331006
TI  - Outbreak Of Extensively Drug Resistant Stenotrophomonas Maltophilia In Burn Unit.
AB  - Stenotrophomonas maltophiliais an emerging cause of nosocomial infections. We
      report an outbreak of XDR-Stenotrophomonas maltophilia infection from burn unit
      of a tertiary care hospital in July 2016. The strain isolated was resistant to
      all antimicrobials tested but colistin. Outbreak investigation was carried out
      which subsided after timely intervention. Patients were treated adequately by
      Colistin.

PMID- 29331007
TI  - Anaesthetic Management Of Nesidioblastosis In Two Infants.
AB  - Nesidioblastosis is the most common cause of non-transient, recurrent and
      persistent hypoglycaemia in neonates and infants. It is a disorder of diffuse
      proliferation of beta cells of the pancreas leading to hyperinsulinemia and
      hypoglycaemia. The main aim is to prevent the severe episodes of hypoglycaemia
      which can cause damage to the brain and/or mental retardation. In this case
      report we present two cases of nesidioblastosis and their perioperative
      anaesthetic course for near-total pancreatectomy. First case was a 7 months old
      female who had repeated episodes of convulsions since birth. Second case was a 4
      month-old female child who again presented with seizures. The challenges faced in
      the perioperative period were the management of perioperative blood glucose
      levels and haemodynamic stability.

PMID- 29331008
TI  - Atypical Presentation Of Rickettsial Spotted Fever.
AB  - Acute febrile illness is a common entity in tropics and often is challenging due
      a host of pathogenic bacteria, viruses and fungi. Extensive work up is required
      for better management. Rickettsiosis is uncommon and hence comes lower down in
      the differentials of multiorgan failure being superseded by the more common
      diseases as malaria, enteric fever and Dengue. We document a case of young male
      presenting with high grade fever, multiorgan dysfunction (hepatic, renal,
      neurological and respiratory involvement), conjunctival suffusion, retiform rash
      and without lymphadenopathy. The diagnosis was further challenging because the
      rashes appeared late at 8th day in the course of illness, unlike the typical
      disease where rashes come on early in day 3-6 of the disease. Patient responded
      to timely treatment with doxycycline. Thus, a high index of suspicion is needed
      to diagnose Rickettsiosis in geographical areas apparently free of the disease.

PMID- 29331009
TI  - Cyanoacrylate Injury To The Ear Canal.
AB  - This is a case regarding a 35-year-old gentleman who presented to the Accident
      and Emergency department at Walsall Manor Hospital. He had mistakenly placed
      cyanoacrylate ('superglue') into his right ear canal in the early morning. In
      terms of its removal, an initial attempt was made in the Ear, Nose and throat
      (ENT) outpatient clinic which proved to be unsuccessful due to the amount of
      discomfort it caused the patient. Therefore, it had to be removed under general
      anaesthesia.

PMID- 29331010
TI  - Implants For Extracapsular Neck Of Femur Fracture Dynamic Hip Screw Versus
      Intramedullary Nailing.
AB  - Neck of femur fractures are the most prevalent type of injury in elderly trauma
      patients. Both intra and extra capsular type of fractures are equally distributed
      in the given population. Traditionally, Extra capsular fractures are fixed with
      Dynamic Hip screw or Intra medullary nailing based on the type of fracture. NICE
      (National Institute of Clinical Excellence) recommends fixing 31-A1 and 31-A2
      fractures with DHS (Dynamic Hip Screw) whereas AO recommends fixing 31-A1 with
      DHS and 31-A2.1 subtype with DHS and 31-A2.2 and 31-A2.3with IMN (Intra medullary
      nail). In regional trauma centre 178 patients, 125 females and 53 males with
      extra capsular neck of femur fractures fixed were selected in a retrospective
      study. The data was spanning over a period of 1 year. Fractures were classified
      as per AO classification by two registrars. The implant selection was analysed in
      terms of the short term out come to find out the cost effectiveness of one over
      the other. The quality of reduction was assessed as per standard criteria and
      consideration of lateral femoral wall thickness was taken into account to assess
      the stability of fracture. The study found more risk of peri prosthetic fractures
      associated with Intra medullary nailing as compared to Dynamic Hip screw and more
      risk of Varus collapse was found to be associated with DHS as compared to IM
      Nail. Moreover, despite of Nail being costly as compared to DHS, the study did
      not reveal its superiority in terms of inpatient hospital stay. In appropriately
      selected patient DHS provides results in terms of hospital stay, revision rate
      and wound complications comparable to IM Nail in the short term justifying its
      use in the above-mentioned fracture patterns as per the standard National
      Institute of clinical Excellence guidelines.

PMID- 29331011
TI  - Transfusion-Related Acute Lung Injury In A Paediatric Intensive Care Unit Of
      Pakistan.
AB  - Background: Transfusion-Related Acute Lung Injury (TRALI) is a major cause of
      transfusionrelated morbidity and mortality in the intensive care unit setting.
      There is a paucity of such data from Pakistan. The purpose of this study is to
      assess the incidence and outcome of TRALI in critically ill children admitted in
      a pediatric intensive care unit (PICU) of Pakistan. Methods: This is a
      retrospective cohort study of all critically ill or injured children who
      developed TRALI or "possible" TRALI after blood transfusion based on Canadian
      Conference Consensus criteria in a closed multidisciplinary-cardiothoracic PICU
      from January 2012 to June 2016. The demographic, pertinent clinical data,
      transfusion-related variables and outcome of all cases of TRALI were recorded.
      Results: Of total 2975 admissions in the PICU during study period, 35.8% (1066)
      received 5124 blood components. Eleven cases developed TRALI in our cohort. The
      incidence of TRALI was 1.03% per patient transfused and 0.19% (19/100,000 per
      blood product transfused). Median age was 8 (range 1-14) yr., 70 % (n=8) were
      male. Mean PRISM-III score was 16.3+/-6.7. Mean time interval for onset of TRALI
      was 2.73+/-1.67 hr. The postoperative cardiac surgical and hematology-oncology
      patients were most common categories (63.6%). Plasma and platelets were the most
      commomly identified trigger of TRALI. The case-specific mortality was 63.6% and
      the overall mortality was 10.7% (p<0.0001). Conclusions: The incidence of TRALI
      in critically ill children is low, but is associated with high mortality.
      Critically ill children with high PRISM-III score, postoperative cardiac surgical
      and hematology-oncology patients are often affected by TRALI.

PMID- 29331012
TI  - Capillary Haemangioma Of Lower Lip In An African Patient.

PMID- 29331013
TI  - Epiploic Appendagitis.

PMID- 29331014
TI  - Biochemical Characterization of Recombinant Thermostable Cohnella sp. A01 beta
      Glucanase
AB  - Background: Typically, non-cellulytic glucanase, including fungi and yeast cell
      wall hydrolyzing enzymes, are released by some symbiotic fungi and plants during
      the mycoparasitic fungi attack on plants. These enzymes are known as the defense
      mechanisms of plants. This study intends to investigate the biochemical
      properties of beta-1,6-glucanase (bg16M) from native thermophilic bacteria,
      Cohnella A01. Methods: bg16M gene was cloned and expressed in E. coli BL21 (DE3).
      The enzyme was purified utilizing Ni-NTA nikcle sepharose column. Pustulan and
      laminarin were selected as substrates in enzyme assay. The purified bg16M enzyme
      was treated with different pH, temperature, metal ions, and detergents. Results:
      The expressed protein, including 639 amino acids, showed a high similarity with
      the hydrolytic glycosylated family 30. The molecular weight of enzyme was 64 kDa,
      and purification yield was 46%. The bg16M demonstrated activity as 4.83 U/ml on
      laminarin and 2.88 U/ml on pustulan. The optimum pH and temperature of the enzyme
      were 8 and 50  degrees C, respectively. The enzyme had an appropriate stability
      at high temperatures and in the pH range of 7 to 9, showing acceptable stability,
      while it did not lose enzymatic activity completely at acidic or basic pH. None
      of the studied metal ions and chemical compounds was the activator of bg16M, and
      urea, SDS, and copper acted as enzyme inhibitors. Conclusion: Biochemical
      characterization of this enzyme revealed that bg16M can be applied in beverage
      industries and medical sectors because of its high activity, as well as thermal
      and alkaline stability.

PMID- 29331017
TI  - Kv4 channels to kisspeptin neurons: 'Let's (not) go steady'.

PMID- 29331016
TI  - A candidate functional SNP rs7074440 in TCF7L2 alters gene expression through C
      FOS in hepatocytes.
AB  - The SNP rs7903146 at the transcription factor 7-like 2 (TCF7L2) locus is
      established as the strongest known genetic marker for type 2 diabetes via genome
      wide association studies. However, the functional SNPs regulating TCF7L2
      expression remain unclear. Here, we show that the SNP rs7074440 is a candidate
      functional SNP highly linked with rs7903146. A reporter plasmid with rs7074440
      normal allele sequence exhibited 15-fold higher luciferase activity compared with
      risk allele sequence in hepatocytes, demonstrating a strong enhancer activity at
      rs7074440. Additionally, we identified C-FOS as an activator binding to the
      rs7074440 enhancer using a TFEL genome-wide screen method. Consistently,
      knockdown of C-FOS significantly reduced TCF7L2 expression in hepatocytes.
      Collectively, a novel enhancer regulating TCF7L2 expression was revealed through
      searching for functional SNPs.

PMID- 29331018
TI  - Interplay of SpkG kinase and the Slr0151 protein in the phosphorylation of
      ferredoxin 5 in Synechocystis sp. strain PCC 6803.
AB  - In Synechocystis 6803, the ferredoxin 5 (Fd5) phosphoprotein and the S/T protein
      kinase SpkG are encoded by the slr0148 and slr0152 genes, respectively, which
      belong to the slr0144-slr0152 cluster. Using a targeted proteomic approach, we
      showed that SpkG is responsible for the phosphorylation of Fd5 on residues T18
      and T72. Sequence alignments and Fd5 structure modelling suggest that these
      phosphorylation events modulate protein-protein interaction. Furthermore, Fd5
      phosphorylation is affected by the Slr0151 protein encoded by the gene preceding
      spkG in the gene cluster. We propose that Slr0151 functions as an auxiliary
      protein in the regulation of the ratio between phosphorylated and
      nonphosphorylated forms of Fd5.

PMID- 29331015
TI  - Detection of human disease conditions by single-cell morpho-rheological
      phenotyping of blood.
AB  - Blood is arguably the most important bodily fluid and its analysis provides
      crucial health status information. A first routine measure to narrow down
      diagnosis in clinical practice is the differential blood count, determining the
      frequency of all major blood cells. What is lacking to advance initial blood
      diagnostics is an unbiased and quick functional assessment of blood that can
      narrow down the diagnosis and generate specific hypotheses. To address this need,
      we introduce the continuous, cell-by-cell morpho-rheological (MORE) analysis of
      diluted whole blood, without labeling, enrichment or separation, at rates of 1000
      cells/sec. In a drop of blood we can identify all major blood cells and
      characterize their pathological changes in several disease conditions in vitro
      and in patient samples. This approach takes previous results of mechanical
      studies on specifically isolated blood cells to the level of application directly
      in blood and adds a functional dimension to conventional blood analysis.

PMID- 29331019
TI  - Cis-regulator runaway and divergence in asexuals.
AB  - With the advent of new sequencing technologies, the evolution of gene expression
      is becoming a subject of intensive genomic research, with sparking debates upon
      the role played by these kinds of changes in adaptive evolution and speciation.
      In this article, we model expression evolution in species differing by their
      reproductive systems. We consider different rates of sexual versus asexual
      reproduction and the different type of parthenogenesis (apomixis and the various
      modes of automixis). We show that competition for expression leads to two
      selective processes on cis-regulatory regions that act independently to organism
      level adaptation. Coevolution within regulatory networks allows these processes
      to occur without strongly modifying expression levels. First, cis-regulatory
      regions such as enhancers evolve in a runaway fashion because they automatically
      become associated to chromosomes purged from deleterious mutations ("Enhancer
      Runaway process"). Second, in clonal or nearly clonal species, homologous cis
      regulatory regions tend to diverge, which leads to haploidization of expression,
      when they are sufficiently isolated from one another ("Enhancer Divergence
      process"). We show how these two processes cooccur and vary depending on the
      level of outcrossing, gene conversion, mitotic recombination, or recombination in
      automictic species. This study offers thus a baseline to understand patterns of
      expression evolution across the diversity of eukaryotic species.

PMID- 29331020
TI  - Human phenotypes caused by PIEZO1 mutations; one gene, two overlapping
      phenotypes?
AB  - PIEZO1 is a large mechanosensitive ion channel protein. Diseases associated with
      PIEZO1 include autosomal recessive generalised lymphatic dysplasia of Fotiou
      (GLDF) and autosomal dominant dehydrated hereditary stomatocytosis with or
      without pseudohyperkalemia and/or perinatal oedema (DHS). The two disorders show
      overlapping features, fetal hydrops/perinatal oedema have been reported in both.
      Electrophysiological studies suggest opposite mechanisms of action: the mutations
      identified in GLDF patients cause a loss-of-function mechanism of disease and
      mutations in DHS patients cause gain of function. This raises the question: Is
      the pathogenic disease mechanism behind the fetal oedema the same in the two
      phenotypes? In this Symposium Review, we will discuss the two conditions and
      highlight key questions that remain to be answered. For instance, the perinatal
      oedema often resolves soon after birth and we are still at a loss to understand
      why. Are there any mechanisms which could compensate for the faulty PIEZO1 in
      these patients? Are there physiological changes at birth that are less reliant on
      the function of PIEZO1? Thus, there is a clear need for further studies into the
      two disorders, in order to fully understand the role of PIEZO1 in health and
      disease.

PMID- 29331021
TI  - Onset, progression and resolution of experimental peri-implant mucositis at
      different abutment surfaces: A randomized controlled two-centre study.
AB  - OBJECTIVES: To assess the onset, progression and resolution of experimentally
      induced peri-implant mucositis lesions at abutments with different
      microstructures in humans. MATERIAL & METHODS: In a randomized, controlled,
      interventional two-centre study, a total of 28 patients had received 28 target
      implants and were randomly allocated to either partially microgrooved (test) or
      machined (control) healing abutments. The study was accomplished in three phases,
      including a wound healing period (WH) following implant placement (12 weeks), a
      plaque exposure phase (EP-21 days) and a resolution phase (RP-16 weeks). Clinical
      (e.g. bleeding on probing-BOP), immunological (MMP-8) and microbiological (DNA
      counts for 11 species) parameters were evaluated. RESULTS: The incidence of peri
      implant mucositis at EPd21 was comparable in both test and control groups (60.0%
      versus 61.5%), but markedly lower at control abutments after a nonsurgical
      treatment and reconstitution of oral hygiene measures at RPw16 (46.7% versus
      15.4%). At any follow-up visit (i.e. EP and RP), clinical parameters, MMP-8
      levels and DNA counts of major bacterial species were not significantly different
      between both groups. CONCLUSION: The onset, progression and resolution of
      experimental peri-implant mucositis lesions were comparable in both groups.

PMID- 29331022
TI  - Open letter to journal editors on: International consensus radiochemistry
      nomenclature guidelines.

PMID- 29331023
TI  - Temozolomide analog PMX 465 downregulates MGMT expression in HCT116 colorectal
      carcinoma cells.
AB  - The efficacy of temozolomide (TMZ) treatment for cancers is currently limited by
      inherent or the development of resistance, particularly, but not exclusively, due
      to the expression of the DNA repair enzyme O6-methylguanine-DNA methyltransferase
      (MGMT) in a significant proportion of tumors. We have found that TMZ analog C8
      methyl imidazole tetrazine (PMX 465) displayed good anticancer activity against
      the colorectal carcinoma HCT116 cells which are MGMT-overexpressing and mismatch
      repair (MMR)-deficient. In this study, we found that PMX 465 could downregulate
      the expression of MGMT in HCT116 cells at the protein and mRNA levels. We found
      that PMX 465 could reduce MGMT expression by increasing the binding of wild-type
      p53 to the MGMT promoter and reducing the binding of Sp1 to the MGMT promoter.

PMID- 29331025
TI  - Multidimensional endotypes of chronic rhinosinusitis and their association with
      treatment outcomes.
AB  - BACKGROUND: The expression of chronic rhinosinusitis (CRS) is multidimensional.
      Disease heterogeneity in patients with CRS remains poorly understood. This study
      aimed to identify endotypes of CRS using cluster analysis by integrating
      multidimensional characteristics and to explore their association with treatment
      outcomes. METHODS: A total of 28 clinical variables and 39 mucosal cellular and
      molecular variables were analyzed using principal component analysis. Cluster
      analysis was performed on 246 prospectively recruited Chinese CRS patients with
      at least 1-year postoperative follow-up. Difficult-to-treat CRS was characterized
      in each generated cluster. RESULTS: Seven subject clusters were identified.
      Cluster 1 (13.01%) was comparable to the classic well-defined eosinophilic CRS
      with polyps, having severe disease and the highest proportion of difficult-to
      treat CRS. Patients in cluster 2 (16.26%) and cluster 4 (13.82%) had relatively
      lower proportions of presence of polyps and presented mild inflammation with
      moderate proportions of difficult-to-treat cases. Subjects in cluster 2 were
      highly atopic. Cluster 3 (7.31%) and cluster 6 (21.14%) were characterized by
      severe or moderate neutrophilic inflammation, respectively, and with elevated
      levels of IL-8 and high proportions of difficult-to-treat CRS. Cluster 5 (4.07%)
      was a unique group characterized by the highest levels of IL-10 and lacked
      difficult-to-treat cases. Cluster 7 (24.39%) demonstrated the lowest symptom
      severity, a low proportion of difficult-to-treat CRS, and low inflammation load.
      Finally, we found that difficult-to-treat CRS was associated with distinct
      clinical features and biomarkers in the different clusters. CONCLUSIONS: Distinct
      clinicopathobiologic clusters of CRS display differences in clinical response to
      treatments and characteristics of difficult-to-treat CRS.

PMID- 29331024
TI  - Combination therapy of lovastatin and AMP-activated protein kinase activator
      improves mitochondrial and peroxisomal functions and clinical disease in
      experimental autoimmune encephalomyelitis model.
AB  - Recent studies report that loss and dysfunction of mitochondria and peroxisomes
      contribute to the myelin and axonal damage in multiple sclerosis (MS). In this
      study, we investigated the efficacy of a combination of lovastatin and AMP
      activated protein kinase (AMPK) activator (AICAR) on the loss and dysfunction of
      mitochondria and peroxisomes and myelin and axonal damage in spinal cords,
      relative to the clinical disease symptoms, using a mouse model of experimental
      autoimmune encephalomyelitis (EAE, a model for MS). We observed that lovastatin
      and AICAR treatments individually provided partial protection of
      mitochondria/peroxisomes and myelin/axons, and therefore partial attenuation of
      clinical disease in EAE mice. However, treatment of EAE mice with the lovastatin
      and AICAR combination provided greater protection of mitochondria/peroxisomes and
      myelin/axons, and greater improvement in clinical disease compared with
      individual drug treatments. In spinal cords of EAE mice, lovastatin-mediated
      inhibition of RhoA and AICAR-mediated activation of AMPK cooperatively enhanced
      the expression of the transcription factors and regulators (e.g. PPARalpha/beta,
      SIRT-1, NRF-1, and TFAM) required for biogenesis and the functions of
      mitochondria (e.g. OXPHOS, MnSOD) and peroxisomes (e.g. PMP70 and catalase). In
      summary, these studies document that oral medication with a combination of
      lovastatin and AICAR, which are individually known to have immunomodulatory
      effects, provides potent protection and repair of inflammation-induced loss and
      dysfunction of mitochondria and peroxisomes as well as myelin and axonal
      abnormalities in EAE. As statins are known to provide protection in progressive
      MS (Phase II study), these studies support that supplementation statin treatment
      with an AMPK activator may provide greater efficacy against MS.

PMID- 29331027
TI  - MiR-137 functions as a tumor suppressor in pancreatic cancer by targeting MRGBP.
AB  - miRNAs are small noncoding RNAs that act as critical epigenetic regulators in
      tumor carcinogenesis. In this study, our data showed that miR-137 was
      significantly downregulated in 58 pairs of human pancreatic cancer (PanCa)
      tissues and PanCa cell lines. Furthermore, the deregulated miR-137 was correlated
      with increased tumor size, higher TNM stage, and worse prognosis in pancreatic
      cancer. Functional studies demonstrated that overexpression of miR-137
      dramatically suppressed cell proliferation and induced cell apoptosis in vitro.
      Meanwhile, upregulated miR-137 remarkably inhibited migration and invasion of
      pancreatic cancer cells. Further studies indicated that MRGBP was identified as
      the direct downstream target gene of miR-137. In addition, MRGBP expression is
      significantly downregulated in miR-137-transfected cells. Our previous study
      revealed that silencing of MRGBP suppressed the growth of PanCa cells in vitro
      and in vivo and also promoted apoptosis, and inhibited migration and invasion of
      PanCa cells, which are consistent with the effects of miR-137 overexpression.
      Taken together, our findings suggest that miR-137 may function as a novel tumor
      promoter through directly targeting MRGBP in PanCa.

PMID- 29331026
TI  - The asthma-rhinitis multimorbidity is associated with IgE polysensitization in
      adolescents and adults.
AB  - BACKGROUND: Children with multimorbid asthma and rhinitis show IgE
      polysensitization to several allergen sources. This association remains poorly
      studied in adolescents and adults using defined allergen molecules. We
      investigated IgE sensitization patterns towards a broad panel of aeroallergen
      components in adults and adolescents with a focus on individuals with asthma and
      rhinitis multimorbidity. METHODS: IgE reactivity to 64 micro-arrayed aeroallergen
      molecules was determined with the MeDALL-chip in samples from the French EGEA
      study (n = 840, age = 40.7 +/- 17.1) and the Swedish population-based birth
      cohort BAMSE (n = 786, age = 16 +/- 0.26). The age- and sex-adjusted associations
      between the number of IgE-reactive allergen molecules (>=0.3 ISU) and the asthma
      rhinitis phenotypes were assessed using a negative binomial model. RESULTS:
      Groups representing 4 phenotypes were identified: no asthma-no rhinitis (A-R-;
      30% in EGEA and 54% in BAMSE), asthma alone (A+R-; 11% and 8%), rhinitis alone (A
      R+; 15% and 24%) and asthma-rhinitis (A+R+; 44% and 14%). The numbers of IgE
      reactive aeroallergen molecules significantly differed between phenotypes (median
      in A-R-, A+R-, A-R+ and A+R+: 0, 1, 2 and 7 in EGEA and 0, 0, 3 and 5 in BAMSE).
      As compared to A-R- subjects, the adjusted ratio of the mean number of IgE
      reactive molecules was higher in A+R+ than in A+R- or A-R+ (10.0, 5.4 and 5.0 in
      EGEA and 7.2, 0.7 and 4.8 in BAMSE). CONCLUSION: The A+R+ phenotype combined the
      sensitization pattern of both the A-R+ and A+R- phenotypes. This multimorbid
      polysensitized phenotype seems to be generalizable to various ages and allergenic
      environments and may be associated with specific mechanisms.

PMID- 29331028
TI  - Alteration in microRNA-17-92 dynamics accounts for differential nature of
      cellular proliferation.
AB  - MicroRNAs associated with the mir-17-92 cluster are crucial regulators of the
      mammalian cell cycle, as they inhibit transcription factors related to the E2F
      family that tightly control decision-making events for a cell to commit for
      active cellular proliferation. Intriguingly, in many solid cancers, these mir-17
      92 cluster members are overexpressed, whereas in some hematopoietic cancers they
      are down-regulated. Our proposed model of the Myc/E2F/mir-17-92 network
      demonstrates that the differential expression pattern of mir-17-92 in different
      cell types can be conceived due to having a contrasting E2F dynamics induced by
      mir-17-92. The model predicts that by explicitly altering the mir-17-92-related
      part of the network, experimentally it is possible to control cellular
      proliferation in a cell type-dependent manner for therapeutic intervention.

PMID- 29331029
TI  - Characterization of CD34+ hematopoietic cells in systemic mastocytosis: Potential
      role in disease dissemination.
AB  - BACKGROUND: Recent studies show that most systemic mastocytosis (SM) patients,
      including indolent SM (ISM) with (ISMs+) and without skin lesions (ISMs-), carry
      the KIT D816V mutation in PB leukocytes. We investigated the potential
      association between the degree of involvement of BM hematopoiesis by the KIT
      D816V mutation and the distribution of different maturation-associated
      compartments of bone marrow (BM) and peripheral blood (PB) CD34+ hematopoietic
      precursors (HPC) in ISM and identified the specific PB cell compartments that
      carry this mutation. METHODS: The distribution of different maturation-associated
      subsets of BM and PB CD34+ HPC from 64 newly diagnosed (KIT-mutated) ISM patients
      and 14 healthy controls was analyzed by flow cytometry. In 18 patients, distinct
      FACS-purified PB cell compartments were also investigated for the KIT mutation.
      RESULTS: ISM patients showed higher percentages of both BM and PB MC-committed
      CD34+ HPC vs controls, particularly among ISM cases with MC-restricted KIT
      mutation (ISMMC ); this was associated with progressive blockade of maturation of
      CD34+ HPC to the neutrophil lineage from ISMMC to multilineage KIT-mutated cases
      (ISMML ). Regarding the frequency of KIT-mutated cases and cell populations in
      PB, variable patterns were observed, the percentage of KIT-mutated PB CD34+ HPC,
      eosinophils, neutrophils, monocytes and T cells increasing from ISMs-MC and
      ISMs+MC to ISMML patients. CONCLUSION: The presence of the KIT D816V mutation in
      PB of ISM patients is associated with (early) involvement of circulating CD34+
      HPC and multiple myeloid cell subpopulations, KIT-mutated PB CD34+ HPC
      potentially contributing to early dissemination of the disease.

PMID- 29331030
TI  - Single-molecule nucleosome remodeling by INO80 and effects of histone tails.
AB  - Genome maintenance and integrity requires continuous alterations of the
      compaction state of the chromatin structure. Chromatin remodelers, among others
      the INO80 complex, help organize chromatin by repositioning, reshaping, or
      evicting nucleosomes. We report on INO80 nucleosome remodeling, assayed by single
      molecule Foerster resonance energy transfer on canonical nucleosomes as well as
      nucleosomes assembled from tailless histones. Nucleosome repositioning by INO80
      is a processively catalyzed reaction. During the initiation of remodeling, probed
      by the INO80 bound state, the nucleosome reveals structurally heterogeneous
      states for tailless nucleosomes (in contrast to wild-type nucleosomes). We,
      therefore, propose an altered energy landscape for the INO80-mediated nucleosome
      sliding reaction in the absence of histone tails.

PMID- 29331031
TI  - Comparative study of efficacy and safety between bladder body and trigonal
      intravesical onabotulinumtoxina injection in the treatment of interstitial
      cystitis refractory to conventional treatment-A prospective, randomized, clinical
      trial.
AB  - PURPOSE: Intravesical onabotulinumtoxinA (BoNT-A) injection can relieve symptoms
      of interstitial cystitis/bladder pain syndrome (IC/BPS). However, the therapeutic
      efficacy of different injection sites is not well known. This study compared
      therapeutic efficacy and safety between bladder body and trigonal BoNT-A
      injection. MATERIALS AND METHODS: Patients were randomly treated with 100U of
      BoNT-A in 10 mL saline injected into 20 bladder body sites or 10 trigonal sites.
      The primary endpoint was changes of Visual Analog Scale (VAS) for Pain at 8th
      week after injection. Secondary endpoint included changes of Global Response
      Assessment (GRA), urinary frequency episodes, O'Leary-Sant score (OSS), and
      urodynamic study. RESULTS: Thirty-nine patients (bladder body, N = 20; trigone, N
      = 19) completed the study visits. Patients in both group had significant
      improvement in VAS, OSS, and functional bladder capacity after treatment. There
      was no significant difference in changes of urinary frequency, voided volume,
      post-void residual volume, and bladder capacity from baseline to 8 weeks between
      groups. Thirteen (65.0%) patients in bladder body group and 10 (52.6%) patients
      in trigone group had decrease of VAS more than 2 points after treatment (P =
      0.43). Excellent symptom improvement (GRA >= 2) was noted in 9 (45%) patients
      with bladder body injection and 10 (52.6%) patients with trigonal injection (P =
      0.63). Nine (45.0%) patients in bladder body group and 10 (52.6%) in trigonal
      group experienced dysuria after treatment (P = 0.52). CONCLUSION: No significant
      difference in the improvement of IC symptoms and urodynamic parameters after
      intravesical BoNT-A injection in the bladder body or trigone. The rate of adverse
      events was similar between groups.

PMID- 29331032
TI  - A split-body study evaluating the efficacy of a conformable surface cryolipolysis
      applicator for the treatment of male pseudogynecomastia.
AB  - BACKGROUND: Cryolipolysis is a non-invasive method of body shaping that has been
      used for male pseudogynecomastia. However, traditional vacuum suction
      cryolipolysis requires a minimum pinchable fat layer which may not always be
      present in this area. OBJECTIVE: To evaluate the efficacy and safety of a
      conformable surface cryolipolysis applicator for the reduction of male
      pseudogynecomastia. MATERIALS AND METHODS: Ten male subjects with
      pseudogynecomastia received two cycles of cryolipolysis to the breast 6 weeks
      apart. Ultrasound was used to measure the thickness of adipose tissue. RESULTS:
      Seven of 10 patients completed the study. Compared to baseline, the mean +/- SD
      change in adipose tissue thickness was 8.12 +/- 6.94 mm for the treated versus
      1.03 +/- 6.03 mm for the control breast at week 6 (p = 0.014), and 8.71 +/- 7.04
      mm for the treated vs. 2.66 +/- 7.04 mm for the control breast at week 12 (P =
      0.16). Four (4) of seven (57%) patients were at least slightly satisfied with the
      treated breast, and although subject satisfaction was higher in the treated
      breast, this did not reach significance (0.085). Adverse events were mild and
      transient. CONCLUSION: A conformable surface cryolipolysis applicator was
      effective in reducing the mean adipose tissue thickness in subjects with male
      pseudogynecomastia. Lasers Surg. Med. (c) 2018 Wiley Periodicals, Inc.

PMID- 29331034
TI  - Effects of in situ selenium exposure and maternal transfer on survival and
      deformities of brown trout (Salmo trutta) fry.
AB  - Offspring of wild adult brown trout exposed to a range of Se concentrations were
      reared in a laboratory setting to primarily assess effects on survival and
      deformities. Maternal whole-body Se concentrations ranged from 4.7 to 22.6 mg/kg
      dry weight for wild fish. Corresponding Se concentrations in embryos ranged from
      6.2 to 40.3 mg/kg dry weight. Significant relationships were found between embryo
      and whole-body tissue concentrations. Increasing egg Se concentrations were
      correlated with decreasing survival; however, hatch success was not significantly
      correlated with increasing embryo Se. The best fit effect concentration, 10%
      (EC10) for survival in the hatch to swim-up period was 20.6 mg/kg dry weight, and
      the EC10 for hatch to test termination at 88 d was 20.5 mg/kg dry weight egg Se.
      The best fit model for deformities was based on a baseline-adjusted severity
      index and resulted in an EC10 of 21.8 mg/kg dry weight egg Se. Both the best fit
      model EC10s represent more sensitive values than the published range of trout
      species EC10s. An egg to whole-body tissue conversion factor derived from the
      paired data resulted in a conversion factor for brown trout of 1.46, which
      resulted in a whole-body tissue EC10 of 14.04 mg/kg dry weight at an egg tissue
      EC10 of 20.5 mg/kg dry weight. Environ Toxicol Chem 2018;37:1396-1408. (c) 2018
      SETAC.

PMID- 29331033
TI  - The efficacy and safety comparison of surgical treatments for stress urinary
      incontinence: A network meta-analysis.
AB  - AIMS: Stress urinary incontinence (SUI) is a common problem worldwide. Mainstream
      surgical procedures include tension-free vaginal tape (TVT), transobturator tape
      (TOT), tension-free vaginal tape-obturator (TVT-O), tension-free vaginal tape
      SECUR (TVT-S), and adjustable single-incision sling (Ajust). The aim of this
      study was to compare the efficacy and safety of these surgical procedures and
      assess which surgery is most optimal for SUI by adopting a network meta-analysis
      (NMA). METHODS: Electronic databases including PubMed, Cochrance Library, and
      Embase database were researched systematically, until March 21, 2017. The
      randomized controlled trials (RCTs) that compared the efficacy and safety of TVT,
      TOT, TVT-O, TVT-S, and Ajust were identified. The studies were included in the
      analysis when met the predefined inclusion criteria. After demographic and
      outcome data extraction, a network meta-analysis was conducted with software R
      3.3.2 and STATA 14.0. Objective cure rate, subjective cure rate, postoperative
      complication rate, bladder perforation, tape erosion, urinary retention, and
      postoperative pain were considered as outcomes, and the outcomes were displayed
      as odds ratios (ORs) and 95% credible intervals (CrI). The consistency of direct
      and indirect evidence was assessed by node splitting. The ranks based on
      probabilities of intervention for the different endpoints were performed.
      RESULTS: Fourty-five RCTs with 7295 participants were analyzed. The NMA results
      revealed that, TVT, TOT, and Ajust had a higher objective cure rate than TVT-O
      and TVT-S (TVT-O: OR = 0.76, 95%CI [0.61, 0.94]; TVT-S: OR = 0.41, 95%CI [0.28,
      0.60]). TVT, TOT, and TVT-O had a superior subjective cure rate than TVT-S and
      Ajust (Ajust: OR = 0.45, 95%CI [0.20, 0.91]; TVT-S: OR = 0.29, 95%CI [0.15,
      0.56]). With TVT as the reference, TVT-S had a statistically lower postoperative
      complication rate (TVT-S: OR = 0.39, 95%CI [0.16, 0.89]). TVT-O, TVT-S, and TOT
      had a significantly lower bladder perforation rate (TOT: OR = 0.076, 95%CI
      [0.0060, 0.37]; TVT-O: OR = 4.1e-17, 95%CI [6.1e-48, 0.0032]; TVT-S: OR = 3.8e
      17, 95%CI [1.8e-48, 0.0052]). There were no obvious differences between the five
      treatments for tape erosion. TVT-O exhibited a less postoperative retention (TVT
      O: OR = 0.35, 95%CI [0.16, 0.74]). Probabilities of ranking results indicated
      that TOT was the treatment with best ranking in efficacy and a relatively high
      safety. CONCLUSIONS: Our study recommend TOT as the optimal regimen for SUI with
      high efficacy and moderate safety when compared with TVT, TVT-O, TVT-S, and Ajust
      interventions. However, with the limitation of our study, additional high-quality
      studies are needed to further evaluate the outcomes.

PMID- 29331035
TI  - Noninvasive optical spectroscopy for identification of non-melanoma skin cancer:
      Pilot study.
AB  - OBJECTIVE: Optical spectroscopy offers a noninvasive alternative to biopsy as a
      first-line screening tool for suspicious skin lesions. This study sought to
      define several optical parameters across malignant and benign tissue types. STUDY
      DESIGN: Prospective pilot trial utilizing the Zenalux IM1 optical spectroscopy
      device from April 2016 to February 2017. For each skin lesion, provider pre
      biopsy probability of malignancy was compared to histolopathologic diagnosis.
      Optical data were characterized across basal cell carcinoma (BCC; n = 9),
      squamous cell carcinoma (SCC; n = 5), actinic keratosis (AK; n = 4), scar tissue
      (n = 6), nevus (n = 2), and neurofibroma (NF; n = 1). Across all patients,
      agreement was determined between control measurements collected adjacent to the
      lesion and from the upper extremity. METHODS: Prospective single center pilot
      study. The optical properties of 27 cutaneous lesions were collected from 18
      adult patients presenting to Otolaryngology and Dermatology clinics with
      suspicious skin lesions warranting biopsy. Spectroscopy measurements were
      recorded for each lesion: two at the lesion site, two at an adjacent site
      (internal control), and one at the central medial upper extremity (arm control).
      Variables of interest included absolute oxygenated hemoglobin (Hb), Hb
      saturation, total Hb concentration, and Eumelanin concentration. For each lesion,
      internal control averages were subtracted from lesion averages to provide delta
      parameter values, and lesion averages were divided by internal control averages
      to provide ratio parameter values. RESULTS: Mean percent difference between pre
      biopsy probability of malignancy and histology was 29%, with a difference of 75%
      or greater seen in 5 of 25 lesions. Mean values for BCC, SCC, AK, and scar tissue
      varied most between extracted mean reduced scatter estimate (MUa'; cm- ) delta
      values (BCC: -2.2 +/- 3.8; SCC: -3.9 +/- 2.0; AK: -3.3 +/- 4.2, Scar: -1.7 +/-
      1.2) and total Hb (uM) ratio (BCC: 2.0 +/- 3.3; SCC: 3.0 +/- 1.3; AK: 1.1 +/-
      0.6; Scar: 1.4 +/- 1.1). Agreement between local and arm controls was poor.
      CONCLUSION: This pilot trial utilizes optical spectroscopy as a noninvasive
      method for determining cutaneous lesion histology. Effect sizes observed across
      optical parameters for benign and malignant tissue types will guide larger
      prospective studies that may ultimately lead to prediction of lesional histology
      without need for invasive biopsy. Lasers Surg. Med. 50:246-252, 2018. (c) 2018
      Wiley Periodicals, Inc.

PMID- 29331036
TI  - Prognostic significance of miR-21 and PDCD4 in patients with stage II esophageal
      carcinoma after surgical resection.
AB  - Many studies have shown that randomized clinical trial with long-term follow-up
      found no improvement in stage II esophageal carcinoma (EC) patients receiving
      preoperative neoadjuvant chemoradiotherapy or chemotherapy treatment, this
      limitation underscored the urgent need for novel and reliable biomarkers for
      prognosis and prediction in stage II EC. miR-21 is frequently over-expressed
      while programmed cell death 4 (PDCD4) is often down-regulated in solid tumors.
      This study aimed to investigate the clinicopathological and prognostic
      significance of miR-21 and PDCD4 expression and to elucidate any correlation
      between miR-21 and PDCD4 expression in stage II EC patients. The expression level
      of miR-21 was up-regulated while the PDCD4 protein was down-regulated in stage II
      EC tissues compared with the adjacent non-cancerous tissues. Analyses of the
      clinicopathological parameters indicated that miR-21 expression was associated
      with differentiation grade, T stage, and N stage. PDCD4 protein expression was
      associated with T stage, N stage, and tumor size. The univariate linear
      regression analysis suggested a significant negative correlation between miR-21
      and PDCD4 expression. The Kaplan-Meier curve showed that high miR-21 expression
      or low PDCD4 expression predicted poor progression-free survival (PFS) and
      overall survival (OS) of patients with stag II EC. In conclusion, both up
      regulated miR-21 and down-regulated PDCD4 expression were associated with the
      aggressive progression and poor prognosis of stage II EC. miR-21 and PDCD4 might
      be potential biomarkers of tumor progression and indicators of prognosis of stag
      II EC.

PMID- 29331037
TI  - Pharmacist Intervention for Blood Pressure Control in Patients with Diabetes
      and/or Chronic Kidney Disease.
AB  - OBJECTIVES: The objectives of this study were to determine if hypertensive
      patients with comorbid diabetes mellitus (DM) and/or chronic kidney disease (CKD)
      receiving a pharmacist intervention had a greater reduction in mean blood
      pressure (BP) and improved BP control at 9 months compared with those receiving
      usual care; and compare Seventh Report of the Joint National Committee on
      Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7)
      guideline and 2014 guideline (JNC 8) BP control rates in patients with DM and/or
      CKD. METHODS: This cluster randomized trial included 32 medical offices in 15
      states. Clinical pharmacists made treatment recommendations to physicians at
      intervention sites. This post hoc analysis evaluated mean BP and BP control rates
      in the intervention and control groups. MAIN RESULTS: The study included 335
      patients (227 intervention, 108 control) when mean BP and control rates were
      evaluated by JNC 7 inclusion and control criteria. When JNC 8 inclusion and
      control criteria were applied, 241 patients (165 intervention, 76 control)
      remained and were included in the analysis. The pharmacist-intervention group had
      significantly greater mean systolic blood pressure reduction compared with usual
      care at 9 months (8.64 mm Hg; 95% confidence interval [CI] -12.8 to -4.49,
      p<0.001). The pharmacist-intervention group had significantly higher BP control
      at 9 months than usual care by either the JNC 7 or JNC 8 inclusion and control
      groups (adjusted odds ratio [OR] 1.97, 95% CI 1.01-3.86, p=0.0470 and OR 2.16,
      95% CI 1.21-3.85, p=0.0102, respectively). PRINCIPAL CONCLUSIONS: This study
      demonstrated that a physician-pharmacist collaborative intervention was effective
      in reducing mean systolic BP and improving BP control in patients with
      uncontrolled hypertension with DM and/or CKD, regardless of which BP guidelines
      were used.

PMID- 29331038
TI  - Modeling strategic sperm allocation: Tailoring the predictions to the species.
AB  - Two major challenges exist when empirically testing the predictions of sperm
      allocation theory. First, the study species must adhere to the assumptions of the
      model being tested. Unfortunately, the common assumption of sperm allocation
      models that females mate a maximum of once or twice does not hold for many, if
      not most, multiply and sequentially mating animals. Second, a model's parameters,
      which dictate its predictions, must be measured in the study species. Common
      examples of such parameters, female mating frequency and sperm precedence
      patterns, are unknown for many species used in empirical tests. Here, we present
      a broadly applicable model, appropriate for multiply, sequentially mating
      animals, and test it in three species for which data on all the relevant
      parameter values are available. The model predicts that relative allocation to
      virgin females, compared to nonvirgins, depends on the interaction between female
      mating rate and the sperm precedence pattern: relative allocation to virgins
      increases with female mating rate under first-male precedence, while the opposite
      is true under later-male precedence. Our model is moderately successful in
      predicting actual allocation patterns in the three species, including a cricket
      in which we measured the parameter values and performed an empirical test of
      allocation.

PMID- 29331039
TI  - Expression of chemerin in the synovial fluid of patients with temporomandibular
      joint disorders.
AB  - The synovial membrane and fluid are significantly involved in the pathogenesis of
      temporomandibular joint (TMJ) disorders. This study aimed to investigate the
      relation between levels of chemerin in the synovial fluid (SF) of patients with
      TMJ disorder and their relationship. Sixty samples of SF were obtained from
      patients with an internal derangement (ID) or osteoarthritis (OA). Chemerin in
      the SF was examined by enzyme-linked immunosorbent assay (ELISA). The results
      showed greater levels of chemerin in the SF of patients with OA than ID. While
      chemerin levels were positively correlated with pain scores, they were inversely
      correlated with MMO. Chemerin levels increased progressively as the disorder
      stage became more severe. The findings of this study suggest that chemerin in SF
      may play role as a predisposing factor and may represent a novel potential
      prognostic biochemical marker in the pathogenesis of TMJ disorders.

PMID- 29331040
TI  - Jun, Gal, Cd74, and C1qb as potential indicator for neuropathic pain.
AB  - Neuropathic pain is a kind of pain caused by primary or secondary impairment or
      dysfunction of peripheral or central nervous system. Patients with neuropathic
      pain were often with poor clinical outcome. We screened the differentially
      expressed genes between sciatic nerve injury and dorsal root ganglion gene in the
      sham operation model. Microarray and the spared nerve injury module were used to
      explore the molecular mechanism of neuropathic pain by injuries and the
      differentially expressed genes (DEGs) were identified out. Besides, the
      bioinformatics methods were used to figure out the signaling pathways and
      expression regulation pattern these DEGs were enriched in, which may provide a
      basis for the molecular research and medicine target of therapy. Besides, protein
      protein interaction network analysis was performed on these selected intersection
      genes. A total of 40 DEGs were screened out and only pctp gene was down
      regulated, the left 39 genes were all up-regulated. Then, GO and KEGG enrichment
      analysis were performed on these intersection genes by DAVID software.
      Furthermore, protein-protein interaction network analysis was used to analyze the
      critical genes of neuropathic pain. Finally, four genes, that is, Jun, Gal, Cd74,
      and C1qb were identified to have strong interactions with other genes, which may
      function as the prognostic and predictive genes of neuropathic pain caused by
      peripheral injuries. Our results suggested that four differentially expressed
      genes, Jun, Gal, Cd74, and C1qb, had the potential to serve as prognostic or
      predictive markers for neuropathic pain, suggesting a potential application in
      the improvement of prognostic tools and treatments.

PMID- 29331041
TI  - Effect of low-level laser therapy on the healing of sites grafted with coagulum,
      deproteinized bovine bone, and biphasic ceramic made of hydroxyapatite and beta
      tricalcium phosphate. In vivo study in rats.
AB  - OBJECTIVE: The aim of this study was to evaluate the effect of low-level laser
      therapy (LLLT) on the healing of biomaterial graft areas (i.e., coagulum,
      deproteinized bovine bone, and biphasic ceramics comprising hydroxyapatite and
      beta-tricalcium phosphate). MATERIAL AND METHODS: Ninety rats were divided into
      two groups according to laser irradiation use (lambda 808 nm, 100 mW, phi ~600
      MUm, seven sessions with 28 J of irradiation dose in total): a laser group and a
      control group. Each of these groups was divided into three subgroups of 15
      animals each according to the type of biomaterial used: Coagulum (COA),
      deproteinized bovine bone (DBB), and hydroxyapatite/beta-tricalcium phosphate
      (HA/betaTCP). Biomaterials were inserted into Teflon domes, and these domes were
      grafted to the lateral aspect of the mandibular branch of the rats. The animals
      were sacrificed after 30, 60, and 90 days. Scarring patterns were evaluated by
      microtomography and histometry. The expression levels of BMP2, osteocalcin (OCN),
      and alkaline phosphatase (ALP) were evaluated by immunohistochemistry. The mRNA
      expression levels of ALP, BMP2, Jagged1, Osterix, Runx2, and TGFbeta1 were
      determined by RT-qPCR. RESULTS: The animals treated with LLLT exhibited increased
      mineralized tissues and bone, particularly after 90 days. These increases were
      associated with increased BMP2, OCN, and ALP protein expression and ALP, BMP2,
      and Jagged1 mRNA expression. CONCLUSION: LLLT improved the osteoconductive
      potential of DBB and HA/betaTCP grafts and bone formation in ungrafted areas.
      Lasers Surg. Med. (c) 2018 Wiley Periodicals, Inc.

PMID- 29331042
TI  - The effects of social context and food abundance on chimpanzee feeding
      competition.
AB  - Feeding competition is thought to play a role in primate social organization as
      well as cognitive evolution. For chimpanzees (Pan troglodytes), social and
      ecological factors can affect competition, yet how these factors interact to
      affect feeding behavior is not fully understood; they can be difficult to
      disentangle in wild settings. This experiment investigated the differential
      effects of food quantity, the presence of a co-feeding partner, and the
      contestability of a food patch on feeding rate. We presented tolerant pairs of
      chimpanzees from a semi-captive social group with an apparatus comprising a
      matrix of transparent tubes between two adjacent rooms, of which, either all
      (abundant condition) or only a small proportion (scarce condition) were baited
      with peanuts. Dyads were either grouped into the competitive treatment, in which
      peanuts were accessible from both sides of the apparatus simultaneously, or the
      non-competitive treatment, in which the peanuts were pre-divided; half of the
      tubes were accessible to one chimpanzee from one side, and the other half were
      accessible only from the opposite side of the apparatus. We compared dyadic
      tolerance levels with individual feeding rates across quantity conditions and
      between competitive treatments. While tolerance and food quantity had no effect
      on feeding rate, partner presence significantly increased feeding rate relative
      to individual feeding. This increase was much larger when the dyads directly
      competed over the peanuts than when they were co-feeding on a pre-divided set of
      peanuts. Thus, in a co-feeding situation, the presence of another individual and,
      to an even larger extent, the contestability of the food source play a larger
      role in chimpanzee feeding behavior than dyadic tolerance or food quantity. These
      findings highlight the relative impact of social facilitation and direct
      competition on co-feeding behavior between pairs of chimpanzees.

PMID- 29331043
TI  - Role of miR-203 in estrogen receptor-mediated signaling in the rat uterus and
      endometrial carcinoma.
AB  - The role of microRNAs (miRNA) in estrogen receptor (ER) signaling in the uterus
      and in endometrial cancer is not well understood. We therefore analyzed miRNA
      expression in uterine samples from a standard 3-day uterotrophic assay using
      young female adult rats to identify E2-regulated miRNAs. Microarray analysis
      identified 47 E2 down-regulated miRNAs including miR-30a, and 25 E2up-regulated
      miRNAs including miR-672, miR-203, and miR-146b. The strongly E2-upregulated miR
      203 was selected for further analysis. miR-203 was deleted in the rat endometrial
      adenocarcinoma cell line, RUCA-I, using CRISPR/CAS9. Five clones devoid of miR
      203 expression were generated. Proliferation was reduced and G2-arrest was
      observed in all miR-203 deficient RUCA-I clones. Transfection with a miR-203-3p
      mimic partially rescues this effect. Comparison of mRNA expression in three miR
      203 knockout clones to wild type RUCA-I cells reveals 566 miR-203-upregulated and
      592 miR-203-downregulated genes. 43 of the genes that are upregulated by miR-203
      knockout in vitro are downregulated in the uterus by E2. Of these Acer2, Zbtb20,
      Ptn, Rcbtb2, Mum1l1, Hmgn3, and Nfat5 possess one or more seed sequence matches
      in their 3'-UTR that are predicted to be targets of miR-203. These data
      demonstrate the importance of E2 regulated miRNAs in general, and miR-203 in
      particular, for E2 regulated gene expression and physiological processes
      including proliferation and cell migration, in the uterus as well as in the
      etiology of endometrial carcinomas.

PMID- 29331044
TI  - Journey of oocyte from metaphase-I to metaphase-II stage in mammals.
AB  - In mammals, journey from metaphase-I (M-I) to metaphase-II (M-II) is important
      since oocyte extrude first polar body (PB-I) and gets converted into haploid
      gamete. The molecular and cellular changes associated with meiotic cell cycle
      progression from M-I to M-II stage and extrusion of PB-I remain ill understood.
      Several factors drive oocyte meiosis from M-I to M-II stage. The mitogen
      activated protein kinase3/1 (MAPK3/1), signal molecules and Rho family GTPases
      act through various pathways to drive cell cycle progression from M-I to M-II
      stage. The down regulation of MOS/MEK/MAPK3/1 pathway results in the activation
      of anaphase-promoting complex/cyclosome (APC/C). The active APC/C destabilizes
      maturation promoting factor (MPF) and induces meiotic resumption. Several signal
      molecules such as, c-Jun N-terminal kinase (JNK2), SENP3, mitotic kinesin-like
      protein 2 (MKlp2), regulator of G-protein signaling (RGS2), Epsin2, polo-like
      kinase 1 (Plk1) are directly or indirectly involved in chromosomal segregation.
      Rho family GTPase is another enzyme that along with cell division cycle (Cdc42)
      to form actomyosin contractile ring required for chromosomal segregation. In the
      presence of origin recognition complex (ORC4), eccentrically localized haploid
      set of chromosomes trigger cortex differentiation and determine the division site
      for polar body formation. The actomyosin contractile activity at the site of
      division plane helps to form cytokinetic furrow that results in the formation and
      extrusion of PB-I. Indeed, oocyte journey from M-I to M-II stage is coordinated
      by several factors and pathways that enable oocyte to extrude PB-I. Quality of
      oocyte directly impact fertilization rate, early embryonic development, and
      reproductive outcome in mammals.

PMID- 29331045
TI  - The urgent need for a harmonized severity scoring system for acute allergic
      reactions.
AB  - The accurate assessment and communication of the severity of acute allergic
      reactions are important to patients, clinicians, researchers, the food industry,
      and public health and regulatory authorities. Severity has different meanings to
      different stakeholders with patients and clinicians rating the significance of
      particular symptoms very differently. Many severity scoring systems have been
      generated, most focusing on the severity of reactions following exposure to a
      limited group of allergens. They are heterogeneous in format, none has used an
      accepted developmental approach, and none has been validated. Their wide range of
      outcome formats has led to difficulties with interpretation and application.
      Therefore, there is a persisting need for an appropriately developed and
      validated severity scoring system for allergic reactions that work across the
      range of allergenic triggers and address the needs of different stakeholder
      groups. We propose a novel approach to develop and then validate a harmonized
      scoring system for acute allergic reactions, based on a data-driven method that
      is informed by clinical and patient experience and other stakeholders'
      perspectives. We envisage two formats: (i) a numerical score giving a continuum
      from mild to severe reactions that are clinically meaningful and are useful for
      allergy healthcare professionals and researchers, and (ii) a three-grade-based
      ordinal format that is simple enough to be used and understood by other
      professionals and patients. Testing of reliability and validity of the new
      approach in a range of settings and populations will allow eventual
      implementation of a standardized scoring system in clinical studies and routine
      practice.

PMID- 29331047
TI  - The economic burden of overactive bladder in the United States: A systematic
      literature review.
AB  - AIMS: Overactive bladder (OAB) affects up to 17% of the United States (US)
      population. This study aimed to synthesize estimates of direct and indirect costs
      of OAB in the US and compare costs among those with and without OAB. METHODS: A
      systematic review was performed using MEDLINE/PubMed and Embase, from 2003 to
      2016, following PRISMA guidelines. The target population was adults with
      idiopathic OAB or urge urinary incontinence from the US. Data were extracted on
      study and patient characteristics, all-cause and OAB-specific direct costs,
      resource use, and indirect costs. Costs were inflated to a common price year of
      2016 USD. RESULTS: Eighteen studies were included. Mean insurer paid all-cause
      total direct healthcare costs ranged from 8168 to 15 569 USD, and OAB-specific
      costs ranged from 656 to 860 USD per-patient annually. Estimates of the
      incremental costs for OAB patients compared to non-OAB comparators ranged from
      43% to 117%. One study estimated total annual indirect costs of OAB at 11 134 USD
      per-patient. CONCLUSIONS: The range of direct healthcare costs reported for
      managing patients with OAB varied, but was relatively small given the differing
      contributing data sources, study designs, and cost definitions. Direct costs were
      consistently higher among patients with OAB versus non-OAB comparisons, from a
      1.4- to >2-fold increase annually. OAB-specific costs made up a small proportion
      of all-cause costs, highlighting the clinical and economic impact of OAB-related
      conditions such as falls, urinary tract infection, and depression. Few studies
      were identified that examined the indirect costs of OAB in the US.

PMID- 29331046
TI  - Prevalence, severity, and risk factors for acute exacerbations of nasal and sinus
      symptoms by chronic rhinosinusitis status.
AB  - BACKGROUND: Nasal and sinus symptoms (NSS) are common to many health conditions,
      including chronic rhinosinusitis (CRS). Few studies have investigated the
      occurrence and severity of, and risk factors for, acute exacerbations of NSS
      (AENSS) by CRS status (current, past, or never met European Position Paper on
      Rhinosinusitis [EPOS] criteria for CRS). METHODS: Four seasonal questionnaires
      were mailed to a stratified random sample of Geisinger primary care patients.
      Logistic regression was used to identify individual characteristics associated
      with AENSS occurrence and severity by CRS status (current long-term, current
      recent, past, never) using EPOS subjective symptoms-only (EPOSS ) CRS criteria.
      We operationalized 3 AENSS definitions based on prescribed antibiotics or oral
      corticosteroids, symptoms, and symptoms with purulence. RESULTS: Baseline and at
      least 1 follow-up questionnaires were available from 4736 subjects. Self-reported
      NSS severity with exacerbation was worst in the current long-term CRS group.
      AENSS was common in all subgroups examined and generally more common among those
      with current EPOSS CRS. Seasonal prevalence of AENSS differed by AENSS definition
      and CRS status. Associations of risk factors with AENSS differed by definition,
      but CRS status, body mass index, asthma, hay fever, sinus surgery history, and
      winter season consistently predicted AENSS. CONCLUSIONS: In this first
      longitudinal, population-based study of 3 AENSS definitions, NSS and AENSS were
      both common, sometimes severe, and differed by EPOSS CRS status. Contrasting
      associations of risk factors for AENSS by the different definitions suggest a
      need for a standardized approach to definition of AENSS.

PMID- 29331048
TI  - Dog bites in a U.S. county: age, body part and breed in paediatric dog bites.
AB  - AIM: To compare characteristics of gender, age, body part and breed in dog bites.
      METHODS: We reviewed 14 956 dog bites (4195 paediatric) reported to the Allegheny
      County Health Department, USA, between 2007 and 2015. Using predefined age
      groups, we performed linear regression to assess for subject age and bite
      frequency and used binary logistic regression to evaluate for differences in
      gender and body part. We used chi-squared test with Bonferroni correction to
      evaluate for differences in reported breeds with age. RESULTS: There was a
      negative correlation (-0.80, r2 = 0.64) between age and bite frequency. Children
      0-3 years had a higher odds ratio (OR) of bites to the face [21.12, 95%
      confidence interval (CI): 17.61-25.33] and a lower OR of bites to the upper (OR:
      0.14, 95% CI: 0.12-0.18) and lower (OR: 0.19, 95% CI: 0.14-0.27) extremities.
      'Pit bulls' accounted for 27.2% of dog bites and were more common in children 13
      18 years (p < 0.01). Shih-Tzu bites were more common in children three years of
      age and younger (p < 0.01). CONCLUSION: Dog bites occur with higher frequency at
      younger ages, and head and neck injuries are more common in younger children. Pit
      bull bites are more common in adolescents and Shih-Tzu bites more common in
      younger children.

PMID- 29331049
TI  - Prenatal maternal psychosocial stress and offspring's asthma and allergic
      disease: A systematic review and meta-analysis.
AB  - BACKGROUND: Prenatal maternal stress may influence offspring's atopic risk
      through sustained cortisol secretion resulting from activation of the
      hypothalamic-pituitary axis (HPA), leading to Th2-biased cell differentiation in
      the foetus. We undertook a systematic review and meta-analysis investigating the
      relationship between prenatal maternal psychosocial stress and risk of asthma and
      allergy in the offspring. METHODS: We searched 11 electronic databases from 1960
      to 2016, searched the grey literature and contacted experts in the field. Type of
      stress indicator included mood disorders, anxiety, exposure to violence,
      bereavement and socio-economic problems occurring during pregnancy, both
      objectively and subjectively measured. We included all possible asthma and IgE
      mediated allergy outcomes. We conducted random-effects meta-analyses to
      synthesize the data. RESULTS: We identified 9779 papers of which 30 studies
      (enrolling >6 million participants) satisfied inclusion criteria. The quality of
      25 studies was moderate, 4 were strong, and one was weak. Maternal exposure to
      any type of stressors was associated with an increased risk of offspring atopic
      eczema/dermatitis (OR 1.34, 95% CI 1.22-1.47), allergic rhinitis (OR 1.30, 95% CI
      1.04-1.62), wheeze (OR 1.34, 95% CI 1.16-1.54) and asthma (OR 1.15, 95% CI 1.04
      1.27). Exposure to anxiety and depression had strongest effect compared to other
      stressors. Exposure during the third trimester had the greatest impact compared
      to first and second trimesters. The increased risk was stronger for early-onset
      and persistent than for late-onset wheeze. Bereavement of a child (HR 1.28, 95%
      CI 1.10-1.48) or a spouse (HR 1.40, 95% CI 1.03-1.90) increased the risk of
      offspring asthma. CONCLUSIONS: Exposure to prenatal maternal psychosocial stress
      was associated with increased risk, albeit modestly, of asthma and allergy in the
      offspring. The pronounced risk during the third trimester may represent
      cumulative stress exposure throughout pregnancy rather than trimester-specific
      effect. Our findings may represent a causal effect or a result of inherent biases
      in studies, particularly residual confounding.

PMID- 29331050
TI  - Exercise counteracts lipotoxicity by improving lipid turnover and lipid droplet
      quality.
AB  - The incidence of obesity and metabolic disease, such as type 2 diabetes mellitus
      (T2D), is rising globally. Dietary lipid over supply leads to lipid accumulation
      at ectopic sites, such as skeletal muscle. Ectopic lipid storage is highly
      correlated with insulin resistance and T2D, likely due to a loss of metabolic
      flexibility - the capacity to switch between fat and glucose oxidation upon
      insulin stimulation - and cellular dysfunction because of lipotoxicity. However,
      muscle lipid levels are also elevated in endurance-trained athletes, presenting a
      paradoxical phenotype of increased intramuscular lipids along with high insulin
      sensitivity - the 'athletes' paradox'. This review focuses on recent human data
      to characterize intramuscular lipid species in order to elucidate some of the
      underlying mechanisms driving skeletal muscle lipotoxicity. There is evidence
      that lipotoxicity is characterized by an increase in bioactive lipid species,
      such as ceramide. The athletes' paradox supports the notion that regular physical
      exercise has health benefits that might originate from the alleviation of
      lipotoxicity. Indeed, exercise training alleviates intramuscular ceramide content
      in obese individuals without a necessary decrease in ectopic lipid storage.
      Furthermore, evidence shows that exercise training elevates markers of lipid
      droplet dynamics such as the PLIN proteins, and triglyceride lipases ATGL and
      HSL, as well as mitochondrial efficiency, potentially explaining the improved
      lipid turnover and a reduction in the accumulation of lipotoxic intermediates
      observed with the athelets' paradox.

PMID- 29331051
TI  - Fecal incontinence knowledge, attitudes, and help-seeking behaviors among
      community-dwelling adults in Korea.
AB  - OBJECTIVES: Fecal incontinence (FI) is a common debilitating disorder that tends
      to be underreported. Although low health literacy likely contributes to the
      underreporting, studies on FI knowledge among the general population remain
      scarce. We investigated how FI knowledge is associated with attitudes and help
      seeking behaviors. METHODS: We conducted a cross-sectional survey among community
      dwelling adults undergoing national health screening in Korea. A structured, self
      administered questionnaire was used to assess FI knowledge, attitudes, and help
      seeking behaviors. Odds ratios (ORs; 95% confidence intervals, CIs) were
      estimated using logistic regression with adjustment for covariables. RESULTS: Of
      the 601 participants completing the survey, only 29.8% were aware of the term FI,
      and their knowledge levels were insufficient. As for FI-related attitudes, 24.6%
      considered FI to be very rare, and 22.3% considered it to be moderately or less
      distressing. Individuals who knew the term FI tended to consider FI more common
      (OR: 2.45; 95%CI: 1.49-4.02) and distressing (OR: 1.68; 95%CI: 1.07-2.63) than
      those without knowledge. Assuming future FI occurrence, those considering FI to
      be distressing were less willing to ignore or self-manage the condition (OR:
      0.25; 95%CI: 0.11-0.58). Among patients with FI (n = 83), only 30.1% had sought
      help and 8.4% had consulted doctors. Knowing the term FI was significantly
      associated with overall help-seeking behavior (OR: 9.23; 95%CI: 2.09-40.77).
      CONCLUSIONS: FI knowledge levels and help-seeking rates were low among community
      dwelling adults. FI knowledge was significantly associated with attitudes and
      help-seeking behaviors. Future public education programs are warranted to improve
      FI knowledge, attitudes, and help-seeking behaviors.

PMID- 29331052
TI  - Flow pattern analysis in type B aortic dissection patients after stent-grafting
      repair: Comparison between complete and incomplete false lumen thrombosis.
AB  - Endovascular stent graft repair has become a common treatment for complicated
      Stanford type B aortic dissection to restore true lumen flow and induce false
      lumen thrombosis. Using computational fluid dynamics, this study reports the
      differences in flow patterns and wall shear stress distribution in complicated
      Stanford type B aortic dissection patients after endovascular stent graft repair.
      Five patients were included in this study: 2 have more than 80% false lumen
      thrombosis (group 1), while 3 others had less than 80% false lumen thrombosis
      (group 2) within 1 year following endovascular repair. Group 1 patients had
      concentrated re-entry tears around the abdominal branches only, while group 2
      patients had re-entry tears that spread along the dissection line. Blood flow
      inside the false lumen which affected thrombus formation increased with the
      number of re-entry tears and when only small amounts of blood that entered the
      false lumen exited through the branches. In those cases where dissection extended
      below the abdominal branches (group 2), patients with fewer re-entry tears and
      longer distance between the tears had low wall shear stress contributing to
      thrombosis. This work provides an insight into predicting the development of
      complete or incomplete false lumen thrombosis and has implications for patient
      selection for treatment.

PMID- 29331054
TI  - ARTIST: A fully automated artifact rejection algorithm for single-pulse TMS-EEG
      data.
AB  - Concurrent single-pulse TMS-EEG (spTMS-EEG) is an emerging noninvasive tool for
      probing causal brain dynamics in humans. However, in addition to the common
      artifacts in standard EEG data, spTMS-EEG data suffer from enormous stimulation
      induced artifacts, posing significant challenges to the extraction of neural
      information. Typically, neural signals are analyzed after a manual time-intensive
      and often subjective process of artifact rejection. Here we describe a fully
      automated algorithm for spTMS-EEG artifact rejection. A key step of this
      algorithm is to decompose the spTMS-EEG data into statistically independent
      components (ICs), and then train a pattern classifier to automatically identify
      artifact components based on knowledge of the spatio-temporal profile of both
      neural and artefactual activities. The autocleaned and hand-cleaned data yield
      qualitatively similar group evoked potential waveforms. The algorithm achieves a
      95% IC classification accuracy referenced to expert artifact rejection
      performance, and does so across a large number of spTMS-EEG data sets (n = 90
      stimulation sites), retains high accuracy across stimulation
      sites/subjects/populations/montages, and outperforms current automated
      algorithms. Moreover, the algorithm was superior to the artifact rejection
      performance of relatively novice individuals, who would be the likely users of
      spTMS-EEG as the technique becomes more broadly disseminated. In summary, our
      algorithm provides an automated, fast, objective, and accurate method for
      cleaning spTMS-EEG data, which can increase the utility of TMS-EEG in both
      clinical and basic neuroscience settings.

PMID- 29331053
TI  - REnal Flow and Microstructure AnisotroPy (REFMAP) MRI in Normal and Peritumoral
      Renal Tissue.
AB  - BACKGROUND: Diffusion-weighted imaging (DWI) provides insight into the
      pathophysiology underlying renal dysfunction. Variants of DWI include intravoxel
      incoherent motion (IVIM), which differentiates between microstructural diffusion
      and vascular or tubular flow, and diffusion tensor imaging (DTI), which
      quantifies diffusion directionality. PURPOSE: To investigate the reproducibility
      of joint IVIM-DTI and compare controls to presurgical renal mass patients. STUDY
      TYPE: Prospective cross-sectional. SUBJECTS: Thirteen healthy controls and ten
      presurgical renal mass patients were scanned. Ten controls were scanned twice to
      investigate reproducibility. FIELD STRENGTH/SEQUENCE: Subjects were scanned on a
      3T system using 10 b-values and 20 diffusion directions for IVIM-DTI in a study
      approved by the local Institutional Review Board. ASSESSMENT: Retrospective
      coregistration and measurement of joint IVIM-DTI parameters were performed.
      STATISTICAL ANALYSIS: Parameter reproducibility was defined as intraclass
      correlation coefficient (ICC) >0.7 and coefficient of variation (CV) <30%.
      Patient data were stratified by lesion side (contralateral/ipsilateral) for
      comparison with controls. Corticomedullary differentiation was evaluated.
      RESULTS: In controls, the reproducible subset of REnal Flow and Microstructure
      AnisotroPy (REFMAP) parameters had average ICC = 0.82 and CV = 7.5%. In renal
      mass patients, medullary fractional anisotropy (FA) was significantly lower than
      in controls (0.227 +/- 0.072 vs. 0.291 +/- 0.044, P = 0.016 for the kidney
      contralateral to the mass and 0.228 +/- 0.070 vs. 0.291 +/- 0.044, P = 0.018 for
      the kidney ipsilateral). In the kidney ipsilateral to the mass, cortical
      Dp,radial was significantly higher than in controls (P = 0.012). Conversely,
      medullary Dp,axial was significantly lower in contralateral than ipsilateral
      kidneys (P = 0.027) and normal controls (P = 0.044). DATA CONCLUSION: REFMAP-MRI
      parameters provide unique information regarding renal dysfunction. In presurgical
      renal mass patients, directional flow changes were noted that were not identified
      with IVIM analysis alone. Both contralateral and ipsilateral kidneys in patients
      show reductions in structural diffusivities and anisotropy, while flow metrics
      showed opposing changes in contralateral vs. ipsilateral kidneys. LEVEL OF
      EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018.

PMID- 29331055
TI  - The challenges and possibilities of public access defibrillation.
AB  - Out-of-hospital cardiac arrest (OHCA) is a major health problem that affects
      approximately four hundred and thousand patients annually in the United States
      alone. It is a major challenge for the emergency medical system as decreased
      survival rates are directly proportional to the time delay from collapse to
      defibrillation. Historically, defibrillation has only been performed by
      physicians and in-hospital. With the development of automated external
      defibrillators (AEDs), rapid defibrillation by nonmedical professionals and
      subsequently by trained or untrained lay bystanders has become possible. Much
      hope has been put to the concept of Public Access Defibrillation with a massive
      dissemination of public available AEDs throughout most Western countries.
      Accordingly, current guidelines recommend that AEDs should be deployed in places
      with a high likelihood of OHCA. Despite these efforts, AED use is in most
      settings anecdotal with little effect on overall OHCA survival. The major reasons
      for low use of public AEDs are that most OHCAs take place outside high incidence
      sites of cardiac arrest and that most OHCAs take place in residential settings,
      currently defined as not suitable for Public Access Defibrillation. However, the
      use of new technology for identification and recruitment of lay bystanders and
      nearby AEDs to the scene of the cardiac arrest as well as new methods for
      strategic AED placement redefines and challenges the current concept and
      definitions of Public Access Defibrillation. Existing evidence of Public Access
      Defibrillation and knowledge gaps and future directions to improve outcomes for
      OHCA are discussed. In addition, a new definition of the different levels of
      Public Access Defibrillation is offered as well as new strategies for increasing
      AED use in the society.

PMID- 29331056
TI  - Exploring the advantages of multiband fMRI with simultaneous EEG to investigate
      coupling between gamma frequency neural activity and the BOLD response in humans.
AB  - We established an optimal combination of EEG recording during sparse multiband
      (MB) fMRI that preserves high-resolution, whole-brain fMRI coverage while
      enabling broad-band EEG recordings which are uncorrupted by MRI gradient
      artefacts (GAs). We first determined the safety of simultaneous EEG recording
      during MB fMRI. Application of MB factor = 4 produced <1 degrees C peak heating
      of electrode/hardware during 20 min of GE-EPI data acquisition. However, higher
      SAR sequences require specific safety testing, with greater heating observed
      using PCASL with MB factor = 4. Heating was greatest in the electrocardiogram
      channel, likely due to it possessing longest lead length. We investigated the
      effect of MB factor on the temporal signal-to-noise ratio for a range of GE-EPI
      sequences (varying MB factor and temporal interval between slice acquisitions).
      We found that, for our experimental purpose, the optimal acquisition was achieved
      with MB factor = 3, 3mm isotropic voxels, and 33 slices providing whole head
      coverage. This sequence afforded a 2.25 s duration quiet period (without GAs) in
      every 3 s TR. Using this sequence, we demonstrated the ability to record gamma
      frequency (55-80 Hz) EEG oscillations, in response to right index finger
      abduction, that are usually obscured by GAs during continuous fMRI data
      acquisition. In this novel application of EEG-MB fMRI to a motor task, we
      observed a positive correlation between gamma and BOLD responses in bilateral
      motor regions. These findings support and extend previous work regarding coupling
      between neural and hemodynamic measures of brain activity in humans and showcase
      the utility of EEG-MB fMRI for future investigations.

PMID- 29331058
TI  - Endoscopic band ligation for colonic diverticular bleeding.

PMID- 29331059
TI  - Neuroanatomical correlates of grit: Growth mindset mediates the association
      between gray matter structure and trait grit in late adolescence.
AB  - There is a long-standing interest in exploring the factors related to student
      achievement. As a newly explored personality trait, grit is defined as a person's
      tendency to pursue long-term goals with continual perseverance and passion, and
      grit plays a critical role in student achievement. Increasing evidence has shown
      that growth mindset, the belief that one's basic abilities are malleable and can
      be developed through effort, is a potential factor for cultivating grit. However,
      less is known about the association between grit and the brain and the role of
      growth mindset in this association. Here, we utilized voxel-based morphometry to
      examine the neuroanatomical correlates of grit in 231 healthy adolescent students
      by performing structural magnetic resonance imaging. The whole-brain regression
      analyses revealed that the regional gray matter volume (rGMV) in the left
      dorsolateral prefrontal cortex (DLPFC) negatively predicted grit. In contrast,
      the rGMV in the right putamen positively predicted grit. Furthermore, mediating
      analyses suggested that growth mindset served as a mediator in the association
      between left DLPFC volume and grit. Our results persisted even after controlling
      for the influences of self-control and delayed gratification. Overall, our study
      presents novel evidence for the neuroanatomical basis of grit and highlights that
      growth mindset might play an essential role in cultivating a student's grit
      level.

PMID- 29331060
TI  - Regional hippocampal vulnerability in early multiple sclerosis: Dynamic
      pathological spreading from dentate gyrus to CA1.
AB  - BACKGROUND: Whether hippocampal subfields are differentially vulnerable at the
      earliest stages of multiple sclerosis (MS) and how this impacts memory
      performance is a current topic of debate. METHOD: We prospectively included 56
      persons with clinically isolated syndrome (CIS) suggestive of MS in a 1-year
      longitudinal study, together with 55 matched healthy controls at baseline.
      Participants were tested for memory performance and scanned with 3 T MRI to
      assess the volume of 5 distinct hippocampal subfields using automatic
      segmentation techniques. RESULTS: At baseline, CA4/dentate gyrus was the only
      hippocampal subfield with a volume significantly smaller than controls (p < .01).
      After one year, CA4/dentate gyrus atrophy worsened (-6.4%, p < .0001) and
      significant CA1 atrophy appeared (both in the stratum-pyramidale and the stratum
      radiatum-lacunosum-moleculare, -5.6%, p < .001 and -6.2%, p < .01, respectively).
      CA4/dentate gyrus volume at baseline predicted CA1 volume one year after CIS (R2 
      = 0.44 to 0.47, p < .001, with age, T2 lesion-load, and global brain atrophy as
      covariates). The volume of CA4/dentate gyrus at baseline was associated with MS
      diagnosis during follow-up, independently of T2-lesion load and demographic
      variables (p < .05). Whereas CA4/dentate gyrus volume was not correlated with
      memory scores at baseline, CA1 atrophy was an independent correlate of episodic
      verbal memory performance one year after CIS (beta = 0.87, p < .05). CONCLUSION:
      The hippocampal degenerative process spread from dentate gyrus to CA1 at the
      earliest stage of MS. This dynamic vulnerability is associated with MS diagnosis
      after CIS and will ultimately impact hippocampal-dependent memory performance.

PMID- 29331061
TI  - Lutolf R, Hughes FM, Jr., Inouye BM, Jin H, McMains JC, Pak ES, Hannan JL, Purves
      JT. NLRP3/IL-1beta mediates denervation during bladder outlet obstruction in
      rats. Neurourology and urodynamics 2017.

PMID- 29331057
TI  - Manifestations and mechanisms of myocardial lipotoxicity in obesity.
AB  - Environmental and socioeconomic changes over the past thirty years have
      contributed to a dramatic rise in the worldwide prevalence of obesity. Heart
      disease is amongst the most serious health risks of obesity, with increases in
      both atherosclerotic coronary heart disease and heart failure among obese
      individuals. In this review, we focus on primary myocardial alterations in
      obesity that include hypertrophic remodelling and diastolic dysfunction. Obesity
      associated perturbations in myocardial and systemic lipid metabolism are
      important contributors to cardiovascular complications of obesity. Accumulation
      of excess lipid in nonadipose cells of the cardiovascular system can cause cell
      dysfunction and cell death, a process known as lipotoxicity. Lipotoxicity has
      been modelled in mice using high-fat diet feeding, inbred lines with mutations in
      leptin receptor signalling, and in genetically engineered mice with enhanced
      myocardial fatty acid uptake, altered lipid droplet homoeostasis or decreased
      cardiac fatty acid oxidation. These studies, along with findings in cell culture
      model systems, indicate that the molecular pathophysiology of lipid overload
      involves endoplasmic reticulum stress, alterations in autophagy, de novo ceramide
      synthesis, oxidative stress, inflammation and changes in gene expression. We
      highlight recent advances that extend our understanding of the impact of obesity
      and altered lipid metabolism on cardiac function.

PMID- 29331062
TI  - Benefits of increasing transpiration efficiency in wheat under elevated CO2 for
      rainfed regions.
AB  - Higher transpiration efficiency (TE) has been proposed as a mechanism to increase
      crop yields in dry environments where water availability usually limits yield.
      The application of a coupled radiation and TE simulation model shows wheat yield
      advantage of a high-TE cultivar (cv. Drysdale) over its almost identical low-TE
      parent line (Hartog), from about -7 to 558 kg/ha (mean 187 kg/ha) over the
      rainfed cropping region in Australia (221-1,351 mm annual rainfall), under the
      present-day climate. The smallest absolute yield response occurred in the more
      extreme drier and wetter areas of the wheat belt. However, under elevated CO2
      conditions, the response of Drysdale was much greater overall, ranging from 51 to
      886 kg/ha (mean 284 kg/ha) with the greatest response in the higher rainfall
      areas. Changes in simulated TE under elevated CO2 conditions are seen across
      Australia with notable increased areas of higher TE under a drier climate in
      Western Australia, Queensland and parts of New South Wales and Victoria. This
      improved efficiency is subtly deceptive, with highest yields not necessarily
      directly correlated with highest TE. Nevertheless, the advantage of Drysdale over
      Hartog is clear with the benefit of the trait advantage attributed to TE ranging
      from 102% to 118% (mean 109%). The potential annual cost-benefits of this
      increased genetic TE trait across the wheat growing areas of Australia (5 year
      average of area planted to wheat) totaled AUD 631 MIL (5-year average wheat price
      of AUD/260 t) with an average of 187 kg/ha under the present climate. The benefit
      to an individual farmer will depend on location but elevated CO2 raises this
      nation-wide benefit to AUD 796 MIL in a 2 degrees C warmer climate, slightly
      lower (AUD 715 MIL) if rainfall is also reduced by 20%.

PMID- 29331063
TI  - Simultaneous pharmacokinetics and stability studies of physalins in rat plasma
      and intestinal bacteria culture media using liquid chromatography with mass
      spectrometry.
AB  - Physalins are the major steroidal constituent of Physalis plants and display a
      range of biological activities. For this study, a rapid and sensitive high
      performance liquid chromatography with triple quadrupole mass spectrometry method
      was developed for the simultaneous quantification of six physalins. Specifically,
      it was for the quantification of physalin A, physalin B, physalin D, physalin G,
      4,7-didehydroneophysalin B, and isophysalin B in rat plasma and rat intestinal
      bacteria. After a solid-phase extraction, analytes and internal standards
      (prednisolone) were separated on a Shield reverse-phase C18 column (measuring 3
      mm * 150 mm with an internal diameter of 3.5 MUm) and determined using multiple
      reactions in a monitoring mode with a positive-ion electrospray ionization
      source. The mobile phase was a mixture of 0.1% formic acid in water (A) and
      acetonitrile (B) and was used at a flow rate of 0.6 mL/min. The intra- and
      interday precisions were within 15% with accuracies ranging from 86.2 to 114%.
      The method was validated and successfully applied to pharmacokinetics and
      stability studies of six physalins in rat plasma and rat intestinal bacteria,
      respectively. The results showed that physalin B and isophysalin B could not be
      absorbed by rats, and rat intestinal bacteria could quickly transform physalins.

PMID- 29331064
TI  - Controlling the Temporal Structure of Brain Oscillations by Focused Attention
      Meditation.
AB  - Our focus of attention naturally fluctuates between different sources of
      information even when we desire to focus on a single object. Focused attention
      (FA) meditation is associated with greater control over this process, yet the
      neuronal mechanisms underlying this ability are not entirely understood. Here, we
      hypothesize that the capacity of attention to transiently focus and swiftly
      change relates to the critical dynamics emerging when neuronal systems balance at
      a point of instability between order and disorder. In FA meditation, however, the
      ability to stay focused is trained, which may be associated with a more
      homogeneous brain state. To test this hypothesis, we applied analytical tools
      from criticality theory to EEG in meditation practitioners and meditation-naive
      participants from two independent labs. We show that in practitioners-but not in
      controls-FA meditation strongly suppressed long-range temporal correlations
      (LRTC) of neuronal oscillations relative to eyes-closed rest with remarkable
      consistency across frequency bands and scalp locations. The ability to reduce
      LRTC during meditation increased after one year of additional training and was
      associated with the subjective experience of fully engaging one's attentional
      resources, also known as absorption. Sustained practice also affected normal
      waking brain dynamics as reflected in increased LRTC during an eyes-closed rest
      state, indicating that brain dynamics are altered beyond the meditative state.
      Taken together, our findings suggest that the framework of critical brain
      dynamics is promising for understanding neuronal mechanisms of meditative states
      and, specifically, we have identified a clear electrophysiological correlate of
      the FA meditation state.

PMID- 29331065
TI  - Component-resolved diagnostics to direct in venom immunotherapy: Important steps
      towards precision medicine.
AB  - Stings of Hymenoptera can induce IgE-mediated systemic and even fatal allergic
      reactions. Venom-specific immunotherapy (VIT) is the only disease-modifying and
      curative treatment of venom allergy. However, choosing the correct venom for VIT
      represents a necessary prerequisite for efficient protection against further
      anaphylactic sting reactions after VIT. In the past, therapeutic decisions based
      on the measurement of specific IgE (sIgE) levels to whole venom extracts were not
      always straightforward, especially when the patient was not able to identify the
      culprit insect. In the last years, the increasing knowledge about the molecular
      structure and relevance of important venom allergens and their availability as
      recombinant allergens, devoid of cross-reactive carbohydrate determinants,
      resulted in the development of an advanced component-resolved diagnostics (CRD)
      approach in venom allergy. Already to date, CRD has increased the sensitivity of
      sIgE detection and enabled the discrimination between primary sensitization and
      cross-reactivity, particularly in patients with sensitization to both honeybee
      and vespid venom. Hence, CRD in many patients improves the selection of the
      appropriate immunotherapeutic intervention. Moreover, the detailed knowledge
      about sensitization profiles on a molecular level might open new options to
      identify patients who are at increased risk of side-effects or not to respond to
      immunotherapy. Therefore, increasing potential of CRD becomes evident, to direct
      therapeutic decisions in a personalized and patient-tailored manner. Reviewed
      here are the state of the art options, recent developments and future
      perspectives of CRD of Hymenoptera venom allergy.

PMID- 29331068
TI  - A fixed partial epithelial-mesenchymal transition (EMT) triggers carcinogenesis,
      whereas asymmetrical division of hybrid EMT cells drives cancer progression.

PMID- 29331066
TI  - Strong evidence for changing fish reproductive phenology under climate warming on
      the Tibetan Plateau.
AB  - Phenological responses to climate change have been widely observed and have
      profound and lasting effects on ecosystems and biodiversity. However, compared to
      terrestrial ecosystems, the long-term effects of climate change on species'
      phenology are poorly understood in aquatic ecosystems. Understanding the long
      term changes in fish reproductive phenology is essential for predicting
      population dynamics and for informing management strategies, but is currently
      hampered by the requirement for intensive field observations and larval
      identification. In this study, a very low-frequency sampling of juveniles and
      adults combined with otolith measurements (long axis length of the first annulus;
      LAFA) of an endemic Tibetan Plateau fish (Gymnocypris selincuoensis) was used to
      examine changes in reproductive phenology associated with climate changes from
      the 1970s to 2000s. Assigning individual fish to their appropriate calendar year
      class was assisted by dendrochronological methods (crossdating). The results
      demonstrated that LAFA was significantly and positively associated with
      temperature and growing season length. To separate the effects of temperature and
      the growing season length on LAFA growth, measurements of larval otoliths from
      different sites were conducted and revealed that daily increment additions were
      the main contributor (46.3%), while temperature contributed less (12.0%). Using
      constructed water-air temperature relationships and historical air temperature
      records, we found that the reproductive phenology of G. selincuoensis was
      strongly advanced in the spring during the 1970s and 1990s, while the increased
      growing season length in the 2000s was mainly due to a delayed onset of winter.
      The reproductive phenology of G. selincuoensis advanced 2.9 days per decade on
      average from the 1970s to 2000s, and may have effects on recruitment success and
      population dynamics of this species and other biota in the ecosystem via the food
      web. The methods used in this study are applicable for studying reproductive
      phenological changes across a wide range of species and ecosystems.

PMID- 29331069
TI  - Cellular Membrane Trafficking Machineries Used by the Hepatitis Viruses.
AB  - While the life cycles of hepatitis viruses (A, B, C, D, and E) have been modestly
      characterized, recent intensive studies have provided new insights. Because these
      viruses "hijack" the membrane trafficking of the host cell machinery during
      replicative propagation, it is essential to determine and understand these
      specific cellular pathways. Hepatitis B virus (HBV) and hepatitis C virus are
      well known as leading causes of liver cirrhosis and hepatocellular carcinoma.
      While substantial inroads toward treating hepatitis C virus patients have
      recently been made, patients with HBV continue to require lifelong treatment,
      which makes a thorough understanding of the HBV life cycle essential.
      Importantly, these viruses have been observed to "hijack" the secretory and
      endocytic membrane trafficking machineries of the hepatocyte. These can include
      the canonical clathrin-mediated endocytic process that internalizes virus through
      cell surface receptors. While these receptors are encoded by the host genome for
      normal hepatocellular functions, they also exhibit virus-specific recognition.
      Further, functions provided by the multivesicular body, which include endosomal
      sorting complexes required for transport, are now known to envelope a variety of
      different hepatitis viruses. In this review, we summarize the recent findings
      regarding the cellular membrane trafficking machineries used by HBV in the
      context of other hepatitis viruses. (Hepatology 2018; 00:000-000).

PMID- 29331070
TI  - How does dose impact on the severity of food-induced allergic reactions, and can
      this improve risk assessment for allergenic foods?: Report from an ILSI Europe
      Food Allergy Task Force Expert Group and Workshop.
AB  - Quantitative risk assessment (QRA) for food allergens has made considerable
      progress in recent years, yet acceptability of its outcomes remains stymied
      because of the limited extent to which it has been possible to incorporate
      severity as a variable. Reaction severity, particularly following accidental
      exposure, depends on multiple factors, related to the allergen, the host and any
      treatments, which might be administered. Some of these factors are plausibly
      still unknown. Quantitative risk assessment shows that limiting exposure through
      control of dose reduces the rates of reactions in allergic populations, but its
      impact on the relative frequency of severe reactions at different doses is
      unclear. Food challenge studies suggest that the relationship between dose of
      allergenic food and reaction severity is complex even under relatively controlled
      conditions. Because of these complexities, epidemiological studies provide very
      limited insight into this aspect of the dose-response relationship. Emerging data
      from single-dose challenges suggest that graded food challenges may overestimate
      the rate of severe reactions. It may be necessary to generate new data (such as
      those from single-dose challenges) to reliably identify the effect of dose on
      severity for use in QRA. Success will reduce uncertainty in the susceptible
      population and improve consumer choice.

PMID- 29331071
TI  - Hepatic PPARalpha function is controlled by polyubiquitination and proteasome
      mediated degradation through the coordinated actions of PAQR3 and HUWE1.
AB  - : Peroxisome proliferator-activated receptor alpha (PPARalpha) is a key
      transcriptional factor that regulates hepatic lipid catabolism by stimulating
      fatty acid oxidation and ketogenesis in an adaptive response to nutrient
      starvation. However, how PPARalpha is regulated by posttranslational modification
      is poorly understood. In this study, we identified that progestin and adipoQ
      receptor 3 (PAQR3) promotes PPARalpha ubiquitination through the E3 ubiquitin
      ligase HUWE1, thereby negatively modulating PPARalpha functions both in vitro and
      in vivo. Adenovirus-mediated Paqr3 knockdown and liver-specific deletion of the
      Paqr3 gene reduced hepatic triglyceride levels while increasing fatty acid
      oxidation and ketogenesis upon fasting. PAQR3 deficiency enhanced the fasting
      induced expression of PPARalpha target genes, including those involved in fatty
      acid oxidation and fibroblast growth factor 21, a key molecule that mediates the
      metabolism-modulating effects of PPARalpha. PAQR3 directly interacted with
      PPARalpha and increased the polyubiquitination and proteasome-mediated
      degradation of PPARalpha. Furthermore, the E3 ubiquitin ligase HUWE1 was
      identified to mediate PPARalpha polyubiquitination. Additionally, PAQR3 enhanced
      the interaction between HUWE1 and PPARalpha. CONCLUSION: Ubiquitination
      modification through the coordinated action of PAQR3 with HUWE1 plays a crucial
      role in regulating the activity of PPARalpha in response to starvation.
      (Hepatology 2018;68:289-303).

PMID- 29331072
TI  - Transcranial Ultrasonographic Image Analysis System for Decision Support in
      Parkinson Disease.
AB  - OBJECTIVES: Transcranial ultrasonography (US) is a relatively new neuroimaging
      modality proposed for early diagnostics of Parkinson disease (PD). The main
      limitation of transcranial US image-based diagnostics is a high degree of
      subjectivity caused by low quality of the transcranial images. The article
      presents a developed image analysis system and evaluates the potential of
      automated image analysis on transcranial US. METHODS: The system consists of
      algorithms for the segmentation and assessment of informative brain regions
      (midbrain and substantia nigra) and a decision support subsystem, which is
      equipped with 64 classification algorithms. Transcranial US images of 191
      participants (118 patients with a clinical PD diagnosis and 73 healthy control
      participants) were analyzed. RESULTS: The diagnostic sensitivity and specificity
      achieved by the proposed system were 85% and 75%, respectively. CONCLUSIONS:
      Digital transcranial US image analysis is challenging, and the application of a
      such system as the sole instrument for decisions in clinical practice remains
      inconclusive. However, the proposed system could be used as a supplementary tool
      for automated assessment of US parameters for decision support in PD diagnostics
      and to reduce observer variability.

PMID- 29331073
TI  - Cerebrospinal fluid macrophage biomarkers in amyotrophic lateral sclerosis.
AB  - OBJECTIVE: The neurodegenerative disease, amyotrophic lateral sclerosis (ALS), is
      a heterogeneous clinical syndrome involving multiple molecular pathways. The
      development of biomarkers for use in therapeutic trials is a priority. We sought
      to use a high-throughput proteomic method to identify novel biomarkers in
      individual cerebrospinal fluid (CSF) samples. METHODS: Liquid
      chromatography/tandem mass spectrometry with label-free quantification was used
      to identify CSF proteins using samples from a well-characterized longitudinal
      cohort comprising patients with ALS (n = 43), the upper motor neuron variant,
      primary lateral sclerosis (PLS; n = 6), and cross-sectional healthy (n = 20) and
      disease controls (Parkinsons' disease, n = 20; ALS mimic disorders, n = 12).
      RESULTS: Three macrophage-derived chitinases showed increased abundance in ALS:
      chitotriosidase (CHIT1), chitinase-3-like protein 1 (CHI3L1), and chitinase-3
      like protein 2 (CHI3L2). Elevated CHI3L1 was common to ALS and PLS, whereas CHIT1
      and CHI3L2 levels differed. Chitinase levels correlated with disease progression
      rate (CHIT1, r = 0.56, p < 0.001; CHI3L1, r = 0.31; p = 0.028; CHI3L2, r = 0.29,
      p = 0.044). CHIT1, CHI3L1, and CHI3L2 levels correlated with phosphorylated
      neurofilament heavy chain (pNFH; r = 0.62, p < 0.001; r = 0.49, p < 0.001; r =
      0.41, p < 0.001). CHI3L1 levels, but not CHIT1 or CHI3L2, increased over time in
      those with low initial levels (gradient = 0.005 log abundance units/month, p =
      0.001). High CHIT1 was associated with shortened survival (hazard ratio [HR]
      2.84; p = 0.009). Inclusion of pNFH in survival models left only an association
      of pNFH and survival (HR 1.26; p = 0.019). INTERPRETATION: Neuroinflammatory
      mechanisms have been consistently implicated through various experimental
      paradigms. These results support a key role for macrophage activity in ALS
      pathogenesis, offering novel target engagement and pharmacodynamic biomarkers for
      neuroinflammation-focused ALS therapy. Ann Neurol 2018;83:258-268.

PMID- 29331074
TI  - Cryopyrin-associated periodic syndrome in early childhood can be successfully
      treated with interleukin-1 blockades.
AB  - : Cryopyrin-associated periodic syndrome (CAPS) is caused by a mutation in the
      NLRP3 gene encoding cryopyrin production. Overproduction of interleukin-1 (IL-1)
      leads to symptoms that are associated with elevated inflammatory markers,
      including periodic fever and a rash. We provide a clinical overview of CAPS in
      children, including three Finnish case studies. CONCLUSION: When CAPS has been
      diagnosed, an IL-1 blockade with biological should be introduced to lessen the
      symptoms and to prevent the progression of organ damage.

PMID- 29331075
TI  - An examination of the clinical outcomes of adolescents and young adults with
      broad autism spectrum traits and autism spectrum disorder and anorexia nervosa: A
      multi centre study.
AB  - OBJECTIVES: To compare the clinical outcomes of adolescents and young adults with
      anorexia nervosa (AN) comorbid with broad autism spectrum disorder (ASD) or ASD
      traits. METHOD: The developmental and well-being assessment and social aptitude
      scale were used to categorize adolescents and young adults with AN (N = 149) into
      those with ASD traits (N = 23), and those who also fulfilled diagnostic criteria
      for a possible/probable ASD (N = 6). We compared both eating disorders specific
      measures and broader outcome measures at intake and 12 months follow-up. RESULTS:
      Those with ASD traits had significantly more inpatient/day-patient service use (p
      = .015), as well as medication use (p < .001) at baseline. Both groups had high
      social difficulties and poorer global functioning (strengths and difficulties
      questionnaire) at baseline, which improved over time but remained higher at 12
      months in the ASD traits group (p = .002). However, the improvement in eating
      disorder symptoms at 12 months was similar between groups with or without ASD
      traits. Treatment completion rates between AN only and ASD traits were similar
      (80.1 vs. 86.5%). DISCUSSION: Adolescents with AN and ASD traits show similar
      reductions in their eating disorder symptoms. Nevertheless, their social
      difficulties remain high suggesting that these are life-long difficulties rather
      than starvation effects.

PMID- 29331076
TI  - Submental artery island flap with simultaneous level I neck dissection.
AB  - BACKGROUND: The purpose of this study was to illustrate the submental island flap
      elevation technique with simultaneous level I neck dissection followed by the
      inset and reconstruction of an oropharyngeal defect. METHODS: A 63-year-old
      patient with a T2N1M0 human papillomavirus-positive squamous cell carcinoma of
      the tonsil was treated with concurrent chemoradiotherapy (cisplatin + 66 Gy). A
      local recurrence 2.5 years after treatment was treated surgically and
      reconstructed with a submental island flap. RESULTS: There were no complications
      and oral diet was initiated at 2 weeks and the gastrostomy tube was removed 1
      month postoperatively. A video demonstration of the submental island flap
      elevation is included with a focus on how levels 1A and 1B can be dissected
      safely and this can be viewed online on Head & Neck's home page at
      http://onlinelibrary.wiley.com/. CONCLUSION: The submental island flap can be
      performed safely with a level I neck dissection for head and neck reconstruction.

PMID- 29331078
TI  - Primary biliary cholangitis, DNA, and beyond: The Relative contribution of genes.

PMID- 29331077
TI  - Optimized paired-sgRNA/Cas9 cloning and expression cassette triggers high
      efficiency multiplex genome editing in kiwifruit.
AB  - Kiwifruit is an important fruit crop; however, technologies for its functional
      genomic and molecular improvement are limited. The clustered regulatory
      interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas)
      system has been successfully applied to genetic improvement in many crops, but
      its editing capability is variable depending on the different combinations of the
      synthetic guide RNA (sgRNA) and Cas9 protein expression devices. Optimizing
      conditions for its use within a particular species is therefore needed to achieve
      highly efficient genome editing. In this study, we developed a new cloning
      strategy for generating paired-sgRNA/Cas9 vectors containing four sgRNAs
      targeting the kiwifruit phytoene desaturase gene (AcPDS). Comparing to the
      previous method of paired-sgRNA cloning, our strategy only requires the synthesis
      of two gRNA-containing primers which largely reduces the cost. We further
      compared efficiencies of paired-sgRNA/Cas9 vectors containing different sgRNA
      expression devices, including both the polycistronic tRNA-sgRNA cassette (PTG)
      and the traditional CRISPR expression cassette. We found the mutagenesis
      frequency of the PTG/Cas9 system was 10-fold higher than that of the CRISPR/Cas9
      system, coinciding with the relative expressions of sgRNAs in two different
      expression cassettes. In particular, we identified large chromosomal fragment
      deletions induced by the paired-sgRNAs of the PTG/Cas9 system. Finally, as
      expected, we found both systems can successfully induce the albino phenotype of
      kiwifruit plantlets regenerated from the G418-resistance callus lines. We
      conclude that the PTG/Cas9 system is a more powerful system than the traditional
      CRISPR/Cas9 system for kiwifruit genome editing, which provides valuable clues
      for optimizing CRISPR/Cas9 editing system in other plants.

PMID- 29331079
TI  - LMOD3-Associated Nemaline Myopathy: Prenatal Ultrasonographic, Pathologic, and
      Molecular Findings.
AB  - To describe the prenatal presentation, including ultrasonographic, histologic,
      and molecular findings, in 2 fetuses affected with LMOD3-related nemaline
      myopathy. Prenatal ultrasonographic examinations and histopathologic studies were
      performed on 2 fetuses with evidence of nemaline myopathy. To establish a
      molecular diagnosis, whole-exome sequencing was pursued for the affected fetuses.
      Nemaline myopathy is a common form of congenital myopathy manifesting with
      nonprogressive generalized muscle weakness, hypotonia, and electron-dense protein
      inclusions in skeletal myofibers. Although clinically, nemaline myopathy can be
      viewed as a common pathway phenotype, its molecular basis is heterogeneous, with
      mutations in 11 identified genes implicated in its pathogenesis so far. Whole
      exome sequencing revealed that the affected fetuses were compound heterozygous
      for 2 newly reported pathogenic variants in the LMOD3 gene, which encodes
      leiomodin 3. To our knowledge, this article is the first report of LMOD3-related
      nemaline myopathy since the original reported cohort. We provide a detailed
      description of the prenatal imaging of these affected fetuses, which we hope, in
      combination with next-generation sequencing, may contribute to further diagnosis
      in additional families.

PMID- 29331080
TI  - Design, Synthesis and Evaluation of Oxazaborine Inhibitors of the NLRP3
      Inflammasome.
AB  - The NLRP3 inflammasome is an important regulator of the sterile inflammatory
      response, and its activation by host-derived sterile molecules leads to the
      intracellular activation of caspase-1, processing of the pro-inflammatory
      cytokines interleukin-1beta (IL-1beta)/IL-18, and pyroptotic cell death.
      Inappropriate activation of NLRP3 drives a chronic inflammatory response and is
      implicated in several non-communicable diseases, including gout, atherosclerosis,
      type II diabetes and Alzheimer's disease. In this study, we report the design,
      synthesis and biological evaluation of novel boron compounds (NBCs) as NLRP3
      inflammasome inhibitors. Structure-activity relationships (SAR) show that 4
      fluoro substituents on the phenyl rings retain NLRP3 inhibitory activity, whereas
      more steric and lipophilic substituents diminish activity. Loss of inhibitory
      activity is also observed if the CCl3 group on the oxazaborine ring is replaced
      by a CF3 group. These findings provide additional understanding of the NBC series
      and will aid in the development of these NLRP3 inhibitors as tool compounds or
      therapeutic candidates for sterile inflammatory diseases.

PMID- 29331081
TI  - Quantitative [Fe]MRI determination of the dynamics of PSMA-targeted SPIONs
      discriminates among prostate tumor xenografts based on their PSMA expression.
AB  - BACKGROUND: There is a need for a quantitative MRI method for iron concentration
      magnetic resonance imaging suitable for measuring the delivery of targeted
      superparamagnetic iron oxide nanoparticles (SPIONs) to tumors. PURPOSE: To apply
      our newly developed [Fe]MRI method to the quantitative imaging in both space and
      time of the iron dynamics of anti-prostate specific membrane antigen (PSMA)
      conjugated SPIONs within human prostate tumor xenografts in nude mice. STUDY
      TYPE: Longitudinal. ANIMAL MODEL: 45 Harlan Sprague Dawley athymic nude mice
      bearing xenografts from PSMA-positive LNCaP, C4-2 and PSMA-negative DU145 tumors
      from human prostate tumor cell lines. FIELD STRENGTH/SEQUENCE: 1.0 Tesla/ T1 and
      T2 weighted spin echo. ASSESSMENT: Image intensity and contrast measurements.
      STATISTICAL TESTS: Student's t-test. RESULTS: The SPION diffusion coefficient
      within tumors was D = 44.8 +/- 2.4 * 10-6 mm2 /s. The iron taken up by PSMA
      positive LNCaP and C4-2 tumors was proportional to the tail-vein injected dose
      from 60 nmol to 1.6 MUmol; injection of 1 MUmol of iron in anti-PSMA conjugated
      SPIONs resulted in a tumor [Fe] of 76 MUM. Even at the highest iron dose of 1.6
      MUmol, the PSMA-negative DU145 tumors took up no significant iron from the anti
      PSMA conjugated SPIONs. A similar lack of nonspecific uptake was observed when
      the antibodies against PSMA were omitted from the injected SPION preparation. The
      fraction of the initial iron dose that was taken up by PSMA-positive tumors was
      2.32 +/- 0.75% (n = 10); uptake by the PSMA-negative DU145 tumors and for SPIONs
      without anti-PSMA antibodies was 0.16 +/- 0.34% (n = 7) giving a ratio of [Fe] in
      PSMA + versus PSMA- tumors greater than 15:1 (P = 0.01). DATA CONCLUSION:
      Quantitative [Fe]MRI of anti-PSMA conjugated SPIONs discriminated between PSMA
      positive LNCaP and C4-2 and PSMA-negative DU145 human prostate tumor xenografts
      in vivo. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging
      2017. J. MAGN. RESON. IMAGING 2018;48:469-481.

PMID- 29331083
TI  - Variation in reproductive outcomes of women with histories of bulimia nervosa,
      anorexia nervosa, or eating disorder not otherwise specified relative to the
      general population and closest-aged sisters.
AB  - OBJECTIVE: This study seeks to examine the long-term reproductive consequences of
      eating disorders (ED), to assess variation in reproductive outcomes by ED type,
      and to examine reproductive differences between women with previous ED diagnosis
      and their discordant sisters. METHOD: Using a sample of women with previous ED
      diagnosis generated by the Utah Population Database, this study compares the
      fecundity (parity) and age at first birth of women by ED subtype (bulimia nervosa
      [BN], anorexia nervosa [AN], and ED not otherwise specified [EDNOS]) (n = 1,579).
      We also employed general population match case-control, and discordant sibling
      pair analyses, to estimate the magnitude of association between EDs and
      reproductive outcomes. RESULTS: Women previously diagnosed with AN or EDNOS
      experienced delayed first birth (HRR = 0.33, HRR = 0.34, respectively) and lower
      parity (IRR = 0.19, IRR = 0.22, respectively) relative to BN (p < .05), the
      general population (p < .05), and closest-aged sisters (p < .05). Women
      previously diagnosed with BN experienced more moderate reductions and delays to
      their reproduction, and had similar reproductive outcomes as their discordant
      sisters. DISCUSSION: Clinicians should consider ED type and family fertility
      histories when addressing the long-term reproductive health needs of women with
      prior AN, BN, or EDNOS diagnosis. Women previously diagnosed with AN or EDNOS
      likely experience the greatest reductions and delays in reproduction across their
      lifespan. Reproductive health screenings may be especially critical for the
      wellbeing of women with a history of AN or EDNOS.

PMID- 29331082
TI  - Mechanistic target of rapamycin complex 1 and 2 in human temporal lobe epilepsy.
AB  - OBJECTIVE: Temporal lobe epilepsy (TLE) is a chronic epilepsy syndrome defined by
      seizures and progressive neurological disabilities, including cognitive
      impairments, anxiety, and depression. Here, human TLE specimens were investigated
      focusing on the mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) and
      complex 2 (mTORC2) activities in the brain, given that both pathways may
      represent unique targets for treatment. METHODS: Surgically resected hippocampal
      and temporal lobe samples from therapy-resistant TLE patients were analyzed by
      western blotting to quantify the expression of established mTORC1 and mTORC2
      activity markers and upstream or downstream signaling pathways involving the two
      complexes. Histological and immunohistochemical techniques were used to assess
      hippocampal and neocortical structural abnormalities and cell-specific expression
      of individual biomarkers. Samples from patients with focal cortical dysplasia
      (FCD) type II served as positive controls. RESULTS: We found significantly
      increased expression of phospho-mTOR (Ser2448), phospho-S6 (Ser235/236), phospho
      S6 (Ser240/244), and phospho-Akt (Ser473) in TLE samples compared to controls,
      consistent with activation of both mTORC1 and mTORC2. Our work identified the
      phosphoinositide 3-kinase and Ras/extracellular signal-regulated kinase signaling
      pathways as potential mTORC1 and mTORC2 upstream activators. In addition, we
      found that overactive mTORC2 signaling was accompanied by induction of two
      protein kinase B-dependent prosurvival pathways, as evidenced by increased
      inhibitory phosphorylation of forkhead box class O3a (Ser253) and glycogen
      synthase kinase 3 beta (Ser9). INTERPRETATION: Our data demonstrate that mTOR
      signaling is significantly dysregulated in human TLE, offering new targets for
      pharmacological interventions. Specifically, clinically available drugs that
      suppress mTORC1 without compromising mTOR2 signaling, such as rapamycin and its
      analogs, may represent a new group of antiepileptogenic agents in TLE patients.
      Ann Neurol 2018;83:311-327.

PMID- 29331084
TI  - British Association of Urological Surgeons (BAUS) consensus document for the
      management of male genital emergencies - penile amputation.
AB  - Male genital emergencies relating to the penis and scrotum are rare and require
      prompt investigation and surgical intervention. Clinicians are often unfamiliar
      with the management of these conditions and may not work in a specialist centre
      with on-site expertise in genitourethral surgery. A series of consensus
      statements have been developed by an expert consensus committee comprising
      members of the British Association of Urological Surgeons (BAUS) Section of
      Andrology and Genitourethral Surgery together with experts from urology units
      throughout the UK. Penile amputation is a rare genital emergency, which requires
      prompt intervention and microsurgical reconstruction. The consensus statements
      will outline the management of these cases for non-specialist units, as well as
      recommendations for reconstruction for specialists.

PMID- 29331085
TI  - Verification of DNA motifs in Arabidopsis using CRISPR/Cas9-mediated mutagenesis.
AB  - Transcription factors (TFs) and chromatin-modifying factors (CMFs) access
      chromatin by recognizing specific DNA motifs in their target genes. Chromatin
      immunoprecipitation followed by next-generation sequencing (ChIP-seq) has been
      widely used to discover the potential DNA-binding motifs for both TFs and CMFs.
      Yet, an in vivo method for verifying DNA motifs captured by ChIP-seq is lacking
      in plants. Here, we describe the use of clustered regularly interspaced short
      palindromic repeat (CRISPR)/CRISPR-associated 9 (Cas9) to verify DNA motifs in
      their native genomic context in Arabidopsis. Using a single-guide RNA (sgRNA)
      targeting the DNA motif bound by REF6, a DNA sequence-specific H3K27 demethylase
      in plants, we generated stable transgenic plants where the motif was disrupted in
      a REF6 target gene. We also deleted a cluster of multiple motifs from another
      REF6 target gene using a pair of sgRNAs, targeting upstream and downstream
      regions of the cluster, respectively. We demonstrated that endogenous genes with
      motifs disrupted and/or deleted become inaccessible to REF6. This strategy should
      be widely applicable for in vivo verification of DNA motifs identified by ChIP
      seq in plants.

PMID- 29331086
TI  - Current management of small bowel obstruction in the UK: results from the
      National Audit of Small Bowel Obstruction clinical practice survey.
AB  - AIM: Small bowel obstruction (SBO) is associated with high rates of morbidity and
      mortality. The National Audit of Small Bowel Obstruction (NASBO) is a
      collaboration between trainees and specialty associations to improve the care of
      patients with SBO through national clinical audit. The aim of this study was to
      define current consultant practice preferences in the management of SBO in the
      UK. METHOD: A survey was designed to assess practice preferences of consultant
      surgeons. The anonymous survey captured demographics, indications for surgery or
      conservative management, use of investigations including water-soluble contrast
      agents (WSCA), use of laparoscopy and nutritional support strategies. The
      questionnaire underwent two pilot rounds prior to dissemination via the NASBO
      network. RESULTS: A total of 384 responses were received from 131 NASBO
      participating units (overall response rate 29.2%). Abdominal CT and serum urea
      and electrolytes were considered essential initial investigations by more than
      80% of consultants. Consensus was demonstrated on indications for early surgery
      and conservative management. Three hundred and thirty-eight (88%) respondents
      would consider use of WSCA; of these, 328 (97.1%) would use it in adhesive SBO.
      Two hundred (52.1%) consultants considered a laparoscopic approach when operating
      for SBO. Oral nutritional supplements were favoured in operatively managed
      patients by 259 (67.4%) respondents compared with conservatively managed patients
      (186 respondents, 48.4%). CONCLUSION: This survey demonstrates consensus on
      imaging requirements and indications for early surgery in the management of SBO.
      Significant variation exists around awareness of the need for nutritional support
      in patients with SBO, and on strategies to achieve this support.

PMID- 29331087
TI  - Outdoor pollen is a trigger of child and adolescent asthma emergency department
      presentations: A systematic review and meta-analysis.
AB  - BACKGROUND: In the context of increased asthma exacerbations associated with
      climatic changes such as thunderstorm asthma, interest in establishing the link
      between pollen exposure and asthma hospital admissions has intensified. Here, we
      systematically reviewed and performed a meta-analysis of studies on pollen and
      emergency department (ED) attendance. METHODS: A search for studies with
      appropriate search strategy in MEDLINE, EMBASE, Web of Science and CINAHL was
      conducted. Each study was assessed for quality and risk of bias. The available
      evidence was summarized both qualitatively and meta-analysed using random-effects
      models when moderate heterogeneity was observed. RESULTS: Fourteen studies were
      included. The pollen taxa investigated differed between studies, allowing meta
      analysis only of the effect of grass pollen. A statistically significant increase
      in the percentage change in the mean number of asthma ED presentations (MPC)
      (pooled results from 3 studies) was observed for an increase in 10 grass pollen
      grains per cubic metre of exposure 1.88% (95% CI = 0.94%, 2.82%). Time series
      studies showed positive correlations between pollen concentrations and ED
      presentations. Age-stratified studies found strongest associations in children
      aged 5-17 years old. CONCLUSION: Exposure to ambient grass pollen is an important
      trigger for childhood asthma exacerbations requiring ED attendance. As pollen
      exposure is increasingly a problem especially in relation to thunderstorm asthma,
      studies with uniform measures of pollen and similar analytical methods are
      necessary to fully understand its impact on human health.

PMID- 29331088
TI  - Significance of circulatory DPP4 activity in metabolic diseases.
AB  - Dipeptidyl peptidase 4 (DPP4), also known as CD26 is a type II transmembrane
      protein that is released from the cell membrane in a nonclassical secretory
      mechanism. This exopeptidase selectively degrades varieties of substrates
      including incretin hormones, growth factors, and cytokines. A significant
      detectable amount of DPP4 activity can be measured in plasma as well as in
      different tissues such as intestinal epithelium, vascular endothelium,
      lymphocytes, monocytes, kidney, liver, adipose, lung, thymus, spleen, prostate,
      etc. Enzymatically active circulatory DPP4 is shed from the plasma membrane via
      proteolytic cleavage, a process responsible for the enhanced plasma DPP4 levels
      and activity. Elevated circulatory DPP4 activity as well as levels has been found
      in wide spectrum of metabolic diseases including diabetes, obesity,
      cardiovascular diseases, and nonalcoholic fatty liver diseases. Moreover, recent
      preclinical studies have further expanded the repertoire for the usage of DPP4
      inhibitors in the treatment of other metabolic diseases and in their consequent
      complications. In the present review we highlight the reason behind the elevated
      circulatory DPP4 levels in metabolic diseases with a focus on the tissue of
      origin. We also underscore the discrepancy of protein levels with enzyme activity
      of circulatory DPP4 in metabolic diseases. (c) 2018 IUBMB Life, 70(2):112-119,
      2018.

PMID- 29331090
TI  - Enhanced chondrogenesis of mesenchymal stem cells over silk fibroin/chitosan
      chondroitin sulfate three dimensional scaffold in dynamic culture condition.
AB  - Chondroitin sulfate (Ch) is one of the main structural components of cartilage
      tissue, therefore, its presence in tissue engineered scaffold is expected to
      enhance cartilage regeneration. Previously, silk fibroin/chitosan (SF/CS) blend
      was proven to be a potential biomaterial for tissue development. In this study,
      the effect of Ch on physicochemical and biological properties of SF/CS blend was
      investigated and scaffolds with 0.8 wt% Ch was found to be favorable. The
      scaffolds possess pore size of 37-212 um, contact angle 46.2-50.3 degrees ,
      showed controlled swelling and biodegradation. The biocompatibility of scaffold
      was confirmed by subcutaneous implantation in mouse. Human mesenchymal stem cells
      (hMSCs) seeded scaffolds cultured under spinner flask bioreactor promoted cell
      attachment, proliferation, distribution, and metabolic activity in vitro. The
      histology and immunofluorescence studies revealed that combined effect of Ch and
      dynamic condition resulted in higher glycosaminoglycan secretion and native
      cartilage type matrix synthesis in comparison to SF/CS scaffolds used as control.
      Higher expression of collagen-II, Sox9, aggrecan and decrease in collagen-I
      expression represented by quantitative polymerase chain reaction study confirmed
      the progression of chondrogenic differentiation. This study successfully
      demonstrates the potentiality of SF/CS-Ch scaffold for hMSCs recruitment and
      redirecting cartilage tissue regeneration with enhanced chondrogenesis. (c) 2018
      Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2576
      2587, 2018.

PMID- 29331089
TI  - Modification of chrysanthemum odour and taste with chrysanthemol synthase induces
      strong dual resistance against cotton aphids.
AB  - Aphids are pests of chrysanthemum that employ plant volatiles to select host
      plants and ingest cell contents to probe host quality before engaging in
      prolonged feeding and reproduction. Changes in volatile and nonvolatile
      metabolite profiles can disrupt aphid-plant interactions and provide new methods
      of pest control. Chrysanthemol synthase (CHS) from Tanacetum cinerariifolium
      represents the first committed step in the biosynthesis of pyrethrin ester
      insecticides, but no biological role for the chrysanthemol product alone has yet
      been documented. In this study, the TcCHS gene was over-expressed in
      Chrysanthemum morifolium and resulted in both the emission of volatile
      chrysanthemol (ca. 47 pmol/h/gFW) and accumulation of a chrysanthemol glycoside
      derivative, identified by NMR as chrysanthemyl-6-O-malonyl-beta-D-glucopyranoside
      (ca. 1.1 mM), with no detrimental phenotypic effects. Dual-choice assays
      separately assaying these compounds in pure form and as part of the headspace and
      extract demonstrated independent bioactivity of both components against the
      cotton aphid (Aphis gossypii). Performance assays showed that the TcCHS plants
      significantly reduced aphid reproduction, consistent with disturbance of aphid
      probing activities on these plants as revealed by electropenetrogram (EPG)
      studies. In open-field trials, aphid population development was very strongly
      impaired demonstrating the robustness and high impact of the trait. The results
      suggest that expression of the TcCHS gene induces a dual defence system, with
      both repellence by chrysanthemol odour and deterrence by its nonvolatile
      glycoside, introducing a promising new option for engineering aphid control into
      plants.

PMID- 29331091
TI  - Terminal spreading depolarization and electrical silence in death of human
      cerebral cortex.
AB  - OBJECTIVE: Restoring the circulation is the primary goal in emergency treatment
      of cerebral ischemia. However, better understanding of how the brain responds to
      energy depletion could help predict the time available for resuscitation until
      irreversible damage and advance development of interventions that prolong this
      span. Experimentally, injury to central neurons begins only with anoxic
      depolarization. This potentially reversible, spreading wave typically starts 2 to
      5 minutes after the onset of severe ischemia, marking the onset of a toxic
      intraneuronal change that eventually results in irreversible injury. METHODS: To
      investigate this in the human brain, we performed recordings with either subdural
      electrode strips (n = 4) or intraparenchymal electrode arrays (n = 5) in patients
      with devastating brain injury that resulted in activation of a Do Not Resuscitate
      Comfort Care order followed by terminal extubation. RESULTS: Withdrawal of life
      sustaining therapies produced a decline in brain tissue partial pressure of
      oxygen (pti O2 ) and circulatory arrest. Silencing of spontaneous electrical
      activity developed simultaneously across regional electrode arrays in 8 patients.
      This silencing, termed "nonspreading depression," developed during the steep
      falling phase of pti O2 (intraparenchymal sensor, n = 6) at 11 (interquartile
      range [IQR] = 7-14) mmHg. Terminal spreading depolarizations started to propagate
      between electrodes 3.9 (IQR = 2.6-6.3) minutes after onset of the final drop in
      perfusion and 13 to 266 seconds after nonspreading depression. In 1 patient,
      terminal spreading depolarization induced the initial electrocerebral silence in
      a spreading depression pattern; circulatory arrest developed thereafter.
      INTERPRETATION: These results provide fundamental insight into the neurobiology
      of dying and have important implications for survivable cerebral ischemic
      insults. Ann Neurol 2018;83:295-310.

PMID- 29331094
TI  - Solvent Impedes CO2 Cycloaddition on Metal-Organic Frameworks.
AB  - The catalytic performance of metal-organic frameworks (MOFs) for the synthesis of
      cyclic carbonate from carbon dioxide and epoxides has been explored under solvent
      and solvent-free conditions, respectively. It was found that MOF catalysts have
      significantly improved catalytic activities in solvent-free CO2 cycloaddition
      reactions than those in solvent. The mechanism was discussed with regard to the
      competition of solvent with substrate to adhere MOF catalysts during the reaction
      process.

PMID- 29331092
TI  - Deep gray matter volume loss drives disability worsening in multiple sclerosis.
AB  - OBJECTIVE: Gray matter (GM) atrophy occurs in all multiple sclerosis (MS)
      phenotypes. We investigated whether there is a spatiotemporal pattern of GM
      atrophy that is associated with faster disability accumulation in MS. METHODS: We
      analyzed 3,604 brain high-resolution T1-weighted magnetic resonance imaging scans
      from 1,417 participants: 1,214 MS patients (253 clinically isolated syndrome
      [CIS], 708 relapsing-remitting [RRMS], 128 secondary-progressive [SPMS], and 125
      primary-progressive [PPMS]), over an average follow-up of 2.41 years (standard
      deviation [SD] = 1.97), and 203 healthy controls (HCs; average follow-up = 1.83
      year; SD = 1.77), attending seven European centers. Disability was assessed with
      the Expanded Disability Status Scale (EDSS). We obtained volumes of the deep GM
      (DGM), temporal, frontal, parietal, occipital and cerebellar GM, brainstem, and
      cerebral white matter. Hierarchical mixed models assessed annual percentage rate
      of regional tissue loss and identified regional volumes associated with time-to
      EDSS progression. RESULTS: SPMS showed the lowest baseline volumes of cortical GM
      and DGM. Of all baseline regional volumes, only that of the DGM predicted time-to
      EDSS progression (hazard ratio = 0.73; 95% confidence interval, 0.65, 0.82; p <
      0.001): for every standard deviation decrease in baseline DGM volume, the risk of
      presenting a shorter time to EDSS worsening during follow-up increased by 27%. Of
      all longitudinal measures, DGM showed the fastest annual rate of atrophy, which
      was faster in SPMS (-1.45%), PPMS (-1.66%), and RRMS (-1.34%) than CIS (-0.88%)
      and HCs (-0.94%; p < 0.01). The rate of temporal GM atrophy in SPMS (-1.21%) was
      significantly faster than RRMS (-0.76%), CIS (-0.75%), and HCs (-0.51%).
      Similarly, the rate of parietal GM atrophy in SPMS (-1.24-%) was faster than CIS
      (-0.63%) and HCs (-0.23%; all p values <0.05). Only the atrophy rate in DGM in
      patients was significantly associated with disability accumulation (beta = 0.04;
      p < 0.001). INTERPRETATION: This large, multicenter and longitudinal study shows
      that DGM volume loss drives disability accumulation in MS, and that temporal
      cortical GM shows accelerated atrophy in SPMS than RRMS. The difference in
      regional GM atrophy development between phenotypes needs to be taken into account
      when evaluating treatment effect of therapeutic interventions. Ann Neurol
      2018;83:210-222.

PMID- 29331093
TI  - Sensitivity to audio-visual synchrony and its relation to language abilities in
      children with and without ASD.
AB  - : Autism Spectrum Disorder (ASD) is often accompanied by deficits in speech and
      language processing. Speech processing relies heavily on the integration of
      auditory and visual information, and it has been suggested that the ability to
      detect correspondence between auditory and visual signals helps to lay the
      foundation for successful language development. The goal of the present study was
      to examine whether young children with ASD show reduced sensitivity to temporal
      asynchronies in a speech processing task when compared to typically developing
      controls, and to examine how this sensitivity might relate to language
      proficiency. Using automated eye tracking methods, we found that children with
      ASD failed to demonstrate sensitivity to asynchronies of 0.3s, 0.6s, or 1.0s
      between a video of a woman speaking and the corresponding audio track. In
      contrast, typically developing children who were language-matched to the ASD
      group, were sensitive to both 0.6s and 1.0s asynchronies. We also demonstrated
      that individual differences in sensitivity to audiovisual asynchronies and
      individual differences in orientation to relevant facial features were both
      correlated with scores on a standardized measure of language abilities. Results
      are discussed in the context of attention to visual language and audio-visual
      processing as potential precursors to language impairment in ASD. Autism Res
      2018, 11: 645-653. (c) 2018 International Society for Autism Research, Wiley
      Periodicals, Inc. LAY SUMMARY: Speech processing relies heavily on the
      integration of auditory and visual information, and it has been suggested that
      the ability to detect correspondence between auditory and visual signals helps to
      lay the foundation for successful language development. The goal of the present
      study was to explore whether children with ASD process audio-visual synchrony in
      ways comparable to their typically developing peers, and the relationship between
      preference for synchrony and language ability. Results showed that there are
      differences in attention to audiovisual synchrony between typically developing
      children and children with ASD. Preference for synchrony was related to the
      language abilities of children across groups.

PMID- 29331095
TI  - Household food insecurity and its association with morbidity report among school
      adolescent in Jimma zone, Ethiopia.
AB  - Background Household food insecurity has a substantial contribution to poor
      health outcomes among young children and adolescents. Food insecurity also
      affects optimal cognitive development and physiological function of these
      vulnerable groups. There is a gap of documented data regarding the association of
      food insecurity and morbidity among school adolescents in Ethiopia. Objective The
      aim of this study is to assess the interrelationship of household food insecurity
      and morbidity report among school adolescent in Jimma zone, Ethiopia. Methods A
      community based cross-sectional study was done from October to November, 2013.
      Data were gathered using structured questionnaires through interview of students
      and their caregivers. A total of 1000 students were selected by using simple
      random sampling methods using their rosters as a frame. Data were also checked
      for missing values and outliers, and analyzed using SPSS version 16.0. Regression
      analyses were used to see the strength of association between independent and
      dependent variables using odds ratios and 95% of confidence intervals. Results
      Adolescents from food insecure households had more reported illness (39.3%) than
      adolescents from food secure households (24.7%) (p < 0.001). Adolescents from
      food insecure households were two times more exposed to morbidity [AOR =
      2.04(1.32, 3.14)] than adolescents from food secure households. This study also
      showed that males had 48% less reported illness [AOR = 0.52(0.01, 0.23)] than
      females. Adolescents who had attended health education had less reported illness
      [AOR = 0.57(0.38, 0.86)] than those who did not ever attend. This study also
      showed that having a farmer [AOR = 0.46(0.28, 0.74)] and government employee [AOR
      = 0.33 (0.17, 0.64)] father were inversely associated with adolescent morbidity.
      Conclusion The findings of this study showed that household food insecurity,
      female gender and lack of attending health education had a significant
      contribution to adolescent morbidity. Therefore, there is a need to improve
      household income earning capacity and strengthen school based health and
      nutrition education to prevent adolescent morbidity. The findings of this study
      can also be used to lead the development of programs aimed at preventing
      adolescent morbidity by notifying policymakers and other stakeholders about the
      association of morbidity with household food insecurity.

PMID- 29331096
TI  - Promoting physical activity and improving dietary quality of Singaporean
      adolescents: effectiveness of a school-based fitness and wellness program.
AB  - Limited data are available on the effectiveness of the school-based structured
      fitness and wellness program to influence dietary quality and physical activity
      levels in Singaporean adolescents. The study examined if a 20-h (over 10 weeks)
      school-based structured fitness and wellness module affects the diet quality
      indices, energy intakes, physical activity levels and the associated energy
      expenditures in a group of healthy, male adolescents with low diet quality and
      physical activity levels. Participant demography, anthropometry, dietary intake
      and daily physical activity were obtained at the beginning, mid-point and end of
      the 10-week program. Physical activity levels were assessed accelerometrically
      over a 1-weekday period. Dietary intake were taken using a structured 7-day food
      diary, and diet quality assessed using the Diet Quality Index-International (DQI
      I). The 31 enrolled participants (age 19.8 +/- 0.6 years) with body mass index
      (BMI) (19.8 +/- 0.6 kg/m2) followed diets of low diet quality scores (48.3 +/-
      9.6 out of 100) and engaged in 3.87 +/- 2.00 h of physical activity daily before
      the start of the intervention. Their dietary quality and physical activity levels
      did not change significantly throughout the intervention period. They scored
      poorly in the moderation and overall balance components of the diet quality
      assessment. The physical activity duration correlated inversely to the diet
      quality scores. Our results suggest that the prescribed school-based fitness and
      wellness module was ineffective in influencing the diet quality and physical
      activity levels of Singaporean male adolescents with low diet quality and
      physical activity levels.

PMID- 29331097
TI  - Vigorous physical activity, perceived stress, sleep and mental health among
      university students from 23 low- and middle-income countries.
AB  - Background Vigorous physical activity (VPA) may be beneficial for mental health.
      The aim of the study was to investigate cross-sectional associations between VPA,
      perceived stress, sleep quality and quantity and mental health among university
      students. Methods In a cross-sectional study, using anonymous questionnaires,
      data was collected from 15122 (42.1% male and 57.9% female) university students
      [mean age 20.6, standard deviation (SD) = 2.0] from 23 countries in the Americas,
      Africa and Asia. They were assessed using the International Physical Activity
      Questionnaire (short version), and measures of sociodemographic, health status,
      health behaviour and anthropometrics. Results Students who met VPA
      recommendations were less likely to report perceived stress, more likely to
      report subjective good health and depression than students without VPA. There was
      no association between VPA and sleep quality and quantity and PTSD symptoms.
      Conclusion This study only found partial benefits of VPA in relation to well
      being of university students.

PMID- 29331098
TI  - Blunted cortisol reactivity and risky driving in young offenders - a pilot study.
AB  - Adolescent risky driving is a significant burden on public health. Young
      offenders (i.e. under custody and supervision of the criminal justice system) may
      be particularly vulnerable, but research is scant. Previous work indicated that
      blunted cortisol reactivity to stress is a marker of risk-taking predisposition,
      including risky driving. In this study, we hypothesized that young offenders
      display higher levels of risky driving than a non-offender comparison group, and
      that cortisol reactivity contributes to the variance in risky driving independent
      of other associated characteristics (i.e. impulsivity, risk taking, alcohol and
      drug use). We found that young offenders (n = 20) showed riskier driving in
      simulation than comparison group (n = 9), and blunted cortisol reactivity was
      significantly associated with risky driving. The results suggest young offenders
      are prone to risky driving, and that individual differences in the cortisol
      stress response may be an explanatory factor.

PMID- 29331099
TI  - Adaptation and validation of the disruptive behaviour disorders teacher rating
      scale as a screening tool for early detection of disruptive behaviour disorders
      in schools in a lower-middle income setting.
AB  - Background Despite the need to curb the menace resulting from the negative
      trajectory of disruptive behaviour disorders (DBD) in societies of the world
      today, there is yet a dearth of locally standardised tools for the early
      detection of these disorders in Nigeria. This study was aimed at standardising
      the DBD teacher rating scale (DBD-TRS) to be culturally specific using teachers'
      ratings of their students. Objectives To establish norm scores for the three
      categories of DBD on the DBD-TRS, to evaluate the reliability, validity,
      predictive power, sensitivity and specificity of DBD-TRS items for identifying
      DBD symptoms amongst children/adolescents between the ages of 4 and 16 years.
      Methods A cross-sectional survey of the five divisions of Lagos was conducted
      using multi-stage sampling technique. A randomly selected sample of teachers from
      a selection of regular schools across the five divisions of Lagos retrospectively
      rated systematically selected samples of their students in absentia; by referring
      to the names in their class registers for the recently concluded school session.
      The DBD-TRS and the previously validated strengths and difficulties questionnaire
      (SDQ) were used for the ratings. Results Ratings were completed for 1508
      children/adolescents by 197 teachers from 30 regular schools. The norm scores for
      the three categories of DBD were determined by gender, age, and grade/class.
      Satisfactory psychometric properties were established for the DBD rating scale.
      All DBD items had high negative predictive power and positive predictive power,
      high specificity, and low false positive rates. However, ADHD items had lower PPP
      (0.23-0.55). Conclusion The DBD rating scale demonstrated sufficient technical
      merits to be used as a preliminary tool for identifying children that may require
      further clinical evaluation by mental health experts for behavioural disorders.

PMID- 29331100
TI  - Prevalence, associated factors, and control level of asthma symptoms among
      adolescents in Northern Jordan.
AB  - Objective To investigate the prevalence, associated factors, and control level of
      asthma in Jordanian high school students. Methods A descriptive, comparative,
      cross sectional design was used and a cluster sample of 2691 students (mean age =
      14.5 years, 51.0% girls), drawn from eight randomly selected public high schools
      in Northern Jordan, participated in the study. Each student had the International
      Study of Asthma and Allergies in Childhood (ISAAC) questionnaire completed in the
      classroom between February and May, 2015. Results The prevalence of recent
      wheezing in the last 12 months was 11.7% whereas the prevalence of diagnosed
      asthma was 6.2%. About 49% of students experienced cough all the time, and 33.5%
      experienced waking up at night due to wheezing some of the time. About 30.9% of
      students reported moderate to big exercise-induced asthma. The mean total Asthma
      Control Test (ACT) score was 5.85 (SD = 3.56) with all of students reporting
      uncontrolled asthma during the last month. Higher rates of asthma symptoms were
      reported by females, 10th graders, and students with negative family history.
      Importantly, students with diagnosed asthma or recent wheezing reported higher
      rates of ever smoking tobacco vs. non-asthmatics (p < 0.000); dual (18.6% vs.
      9.8%), cigarettes only (11.2% vs. 7.3%), and waterpipe only (18.0% vs. 14.7%).
      Conclusion Overall, students with asthma or wheezing had increased rates of
      tobacco smoking. Policies need to be set and enforced to provide a better
      environment for these youth, especially making all schools smoke-free zones. A
      multifaceted, comprehensive awareness and management program is required in
      schools to control and manage asthma symptoms.

PMID- 29331101
TI  - Theory analysis for Pender's health promotion model (HPM) by Barnum's criteria: a
      critical perspective.
AB  - Background Analysis of nursing theoretical works and its role in knowledge
      development is presented as an essential process of critical reflection. Health
      promotion model (HPM) focuses on helping people achieve higher levels of well
      being and identifies background factors that influence health behaviors.
      Objectives This paper aims to evaluate, and critique HPM by Barnum's criteria.
      Methods The present study reviewed books and articles derived from Proquest,
      PubMed, Blackwell Databases. The method of evaluation for this model is based on
      Barnum's criteria for analysis, application and evaluation of nursing theories.
      The criteria selected by Barnum embrace both internal and external criticism.
      Internal criticism deals with how theory components fit with each other (internal
      construction of theory) and external criticism deals with the way in which theory
      relates to the extended world (which considers theory in its relationships to
      human beings, nursing, and health). Results The electronic database search
      yielded over 27,717 titles and abstracts. Following removal of duplicates, 18,963
      titles and abstracts were screened using the inclusion criteria and 1278
      manuscripts were retrieved. Of these, 80 were specific to HPM and 23 to analysis
      of any theory in nursing relating to the aim of this article. After final
      selection using the inclusion criteria for this review, 28 manuscripts were
      identified as examining the factors contributing to theory analysis. Evaluation
      of health promotion theory showed that the philosophical claims and their content
      are consistent and clear. HPM has a logical structure and was applied to diverse
      age groups from differing cultures with varying health concerns. Conclusion In
      conclusion, among the strategies for theory critique, the Barnum approach is
      structured and accurate, considers theory in its relationship to human beings,
      community psychiatric nursing, and health. While according to Pender, nursing
      assessment, diagnosis and interventions are utilized to operationalize the HPM
      through practical application and research.

PMID- 29331102
TI  - Opposite-sex relationship questionnaire for female adolescents: development and
      psychometric evaluation.
AB  - Aim The goal of the present study is to adopt state-of-the-art techniques and
      standards to develop and evaluate a measure, called the opposite-sex relationship
      questionnaire for female adolescents (OSRQFA), to assess the reasons why
      adolescent girls would or would not develop, a relationship with an adolescent
      boy. Methods A mixed-method, sequential, exploratory design was adopted. In the
      qualitative phase, an in-depth interview approach was used to identify the
      properties and dimensions to be included in the OSRQFA. In the quantitative
      phase, the psychometric properties of the OSRQFA were evaluated according to
      face, content and construct validity. Reliability and stability were assessed
      with Cronbach's alpha and test-retest analysis, respectively. Results A
      preliminary questionnaire including 86 items which emerged from the qualitative
      phase of the study was designed. Based on the impact scores for face validity and
      the cutoff points for the content validity ratio (CVR) and content validity index
      (CVI), the preliminary questionnaire was reduced to 57 items. The Kaiser criteria
      (eigenvalues >1) and scree plot tests demonstrated that 21 items forming six
      factors, which were labeled 'innate predilection', 'abstinence', 'peer pressure',
      'fear of the relationship consequences', 'family atmosphere' and 'risk taking',
      that accounted for an estimated 66.19% of variance provided an optimal fit with
      the data. These scales had acceptable levels of internal consistency (alpha =
      0.822) and stability (r = 0.871, p < 0.001). Conclusion The OSRQFA with 21 items
      and 6 factors demonstrated suitable validity and reliability in a sample of
      Iranian female adolescents. The OSRQFA's has good psychometric properties, and
      can be used by other researchers in future studies.

PMID- 29331103
TI  - Comparison of coronary risk factors and angiographic findings in younger and
      older patients with significant coronary artery disease.
AB  - BACKGROUND: Coronary artery disease (CAD) is uncommon among young adults and may
      have certain characteristics that are different from those in older patients. The
      aim of the current study was to determine the risk factors of CAD, important
      laboratory data and angiographic findings in young patients with CAD and to
      compare them with the old patients. METHODS: Patients with typical chest pain
      whose CAD was confirmed by coronary angiography were included in the study. These
      patients were divided into 2 groups: >= 45 and < 45 years old; the risk factors
      of CAD and angiographic findings were determined in each group and further
      compared. RESULTS: Finally, 231 patients with CAD were included in the study.
      Thirty-five (30.4%) of patients younger than 45 years and 58 (50.0%) aged >= 45
      had diabetes mellitus (P = 0.002). Statistically remarkable differences were
      observed between the two groups regarding hypertension (P < 0.001), myocardial
      infarction (P < 0.001), Gensini score Median (P < 0.001), ejection fraction in
      echocardiography (P < 0.001) and fasting blood sugar in laboratory data (P =
      0.006). The older group, compared with the younger one, had higher left anterior
      descending (LAD) artery (P < 0.001), right coronary artery (RCA) (P < 0.001), 3
      vessel disease (P < 0.001) and 2-vessel disease (P = 0.044); on the other hand, 1
      vessel disease was higher in patients aged < 45(P < 0.001). CONCLUSION: The risk
      profile and angiographic findings are different in young patients with CAD
      compared to older patients. Young patients with CAD tend to be male with a
      positive familial history, but with less diabetes or hypertension. The older
      patients had higher 3 vessel disease, 2-vessel disease and left anterior
      descending (LAD) artery and right coronary artery (RCA) involvements. In
      contrast, 1-vessel disease was higher in young patients aged <45.

PMID- 29331105
TI  - Dietary Factors Modulate Colonic Tumorigenesis Through the Interaction of Gut
      Microbiota and Host Chloride Channels.
AB  - SCOPE: In recent decades, the association among diet, gut microbiota, and the
      risk of colorectal cancer (CRC) has been established. Gut microbiota and
      associated metabolites, such as bile acids and butyrate, are now known to play a
      key role in CRC development. The aim of this study is to identify that the
      progression to CRC is influenced by cholic acid, sodium butyrate, a high-fat
      diet, or different dose of dihydromyricetin (DMY) interacted with gut microbiota.
      METHODS AND RESULTS: An AOM/DSS (azoxymethan/dextran sodium sulfate) model is
      established to study the gut microbiota compsition before and after tumor
      formation during colitis-induced tumorigenesis. All above dietary factors
      profoundly influence the composition of gut microbiota and host colonic
      tumorigenesis. In addition, mice with DMY-modified initial microbiota display
      different degrees of chemically induced tumorigenesis. Mechanism analysis reveals
      that gut microbiota-associated chloride channels participated in colon
      tumorigenesis. CONCLUSION: Gut microbiota changes occur in the hyperproliferative
      stage before tumor formation. Gut microbiota and host chloride channels, both of
      which are regulated by dietary factors, are associated with CRC development.

PMID- 29331104
TI  - Inhibition of mircoRNA-34a Enhances Survival of Human Bone Marrow Mesenchymal
      Stromal/Stem Cells Under Oxidative Stress.
AB  - BACKGROUND Mesenchymal stromal/stem cells (MSCs) are broadly used for many
      diseases, but the efficacy of MSC engraftment is very low due to low viability
      and high cell death rate under a stressful microenvironment. The present study
      aimed to investigate whether microRNA-34a (miR-34a), which is a downstream target
      of P53, is involved in H2O2-induced MSC cell death. MATERIAL AND METHODS Human
      bone marrow MSCs (hMSCs) were purchased from Lonza and were cultured as
      previously described. hMSCs were transfected with miR-34a inhibitor and exposed
      to H2O2. Cell proliferation assay was used to assess the survival rate of hMSCs.
      Real-time PCR and Western blot analysis were used to examine proliferation and
      survival ability of hMSCs. RESULTS H2O2 exposure significantly increased miR-34a
      expression in human bone marrow MSCs. H2O2 challenge induced massive MSC cell
      death along with reduction of expression of proliferation marker Ki67 and
      survival-related genes Bcl-2 and Survivin. Transfection of miR-34a inhibitor anti
      34a led to a significant protective effect and rescued MSC cell death triggered
      by H2O2 exposure by 50%. Moreover, anti-34a dramatically increased Bcl-2 and Ki67
      mRNA expression levels by over 10-fold compared to the mock control group under
      H2O2 exposure. The protein levels of Bcl-2 and Survivin were also rescued by anti
      34a treatment by 50%. CONCLUSIONS Our results suggest that miR-34a plays a key
      role in oxidative stress-induced MSC cell death, and targeting miR-34a might be a
      promising strategy to enhance the survival rate of engrafted stem cells, which
      may improve therapeutic outcome.

PMID- 29331106
TI  - Kbtbd2 inhibits the cytotoxic activity of immortalized NK cells through down
      regulating mTOR signaling in a mouse hepatocellular carcinoma model.
AB  - Natural killer cell (NK cell)-based immunotherapy is a promising therapeutic
      strategy for hepatocellular carcinoma (HCC). However, the molecular mechanisms
      underlying the regulation of NK cell function in the tumor sites are not
      completely elucidated. In this study, we identified the enhanced expression of
      kelch repeat and BTB (POZ) domain containing 2 (Kbtbd2) in intratumoral NK cells
      in a mouse HCC implantation model as a negative regulator of NK cells. To
      investigate this interaction, we used a Tet-on inducible expression system to
      control Kbtbd2 expression in an immortalized mouse NK cell line KIL C.2. With
      this approach, we found that overexpression of Kbtbd2 reduced KIL C.2 cell
      proliferation, decreased expression certain of Ly49 receptor family members, and
      substantially impaired cytotoxic activity of KIL C.2 cells in vitro. Moreover,
      phosphorylation of mTOR and its target 4E-binding protein 1 was reduced in Kbtbd2
      expressing KIL C.2 cells, along with down-regulated phosphorylation of Erk1/2.
      Adoptively transferred Kbtbd2-expressing KIL C.2 cells exhibited weaker
      tumoricidal effect on hepatocellular carcinoma cells in the HCC implantation
      model, in comparison with transferred control KIL C.2 cells. Taken together, our
      investigation indicates that Kbtbd2 is an inhibitory molecule for the tumoricidal
      activity of KIL C.2 cells and perhaps intratumoral NK cells.

PMID- 29331107
TI  - Endoscopic Full-Thickness Resection Combined with Laparoscopic Surgery.
AB  - Endoscopic full-thickness resection combined with laparoscopic surgery was
      recently developed. These procedures could be categorized as "Cut first and then
      suture" and "Suture first and then cut". "Cut first and then suture" includes
      laparoscopic and endoscopic cooperative surgery (LECS) and laparoscopy-assisted
      endoscopic full-thickness resection (LAEFR). Recent studies have demonstrated the
      safety and efficacy of LECS and LAEFR. However, these techniques are limited by
      the related exposure of the tumor and gastric mucosa to the peritoneal cavity and
      manipulation of these organs, which could lead to viable cancer cell seeding and
      the spillage of gastric juice into the peritoneal cavity. In the "Suture first
      and then cut" technique, the serosal side of the stomach is sutured to invert the
      stomach and subsequently endoscopic resection is performed. In this article,
      details of these techniques, including their advantages and limitations, are
      described.

PMID- 29331108
TI  - Classical molecular dynamics simulation of microwave heating of liquids: The case
      of water.
AB  - We perform a complete classical molecular dynamics study of the dielectric
      heating of water in the microwave (MW) region. MW frequencies ranging from 1.0 to
      15.0 GHz are used together with a series of well-known empirical force fields. We
      show that the ability of an empirical force field to correctly predict the
      dielectric response of liquids to MW radiation should be evaluated on the basis
      of a joint comparison of the predicted and experimental static dielectric
      constant, frequency-dependent dielectric spectra, and heating profiles. We argue
      that this is essential when multicomponent liquids are studied. We find that both
      the three-site OPC3 and four-site TIP4P-epsilon empirical force fields of water
      are equally superior for reproducing dielectric properties at a range of MW
      frequencies. Despite its poor prediction of the static dielectric constant, the
      well-known SPCE force field can be used to accurately describe dielectric heating
      of water at low MW frequencies.

PMID- 29331109
TI  - Interaction of C2H with molecular hydrogen: Ab initio potential energy surface
      and scattering calculations.
AB  - The potential energy surface (PES) describing the interaction of the ethynyl
      (C2H) radical in its ground X2Sigma+ electronic state with molecular hydrogen has
      been computed through restricted coupled cluster calculations including single,
      double, and (perturbative) triple excitations [RCCSD(T)], with the assumption of
      fixed molecular geometries. The computed points were fit to an analytical form
      suitable for time-independent quantum scattering calculations of rotationally
      inelastic cross sections and rate constants. A representative set of energy
      dependent state-to-state cross sections is presented and discussed. The PES and
      cross sections for collisions of H2(j = 0) are compared with a previous study [F.
      Najar et al., Chem. Phys. Lett. 614, 251 (2014)] of collisions of C2H with H2
      treated as a spherical collision partner. Good agreement is found between the two
      sets of calculations when the H2 molecule in the present calculation is
      spherically averaged.

PMID- 29331110
TI  - Random sequential adsorption of cubes.
AB  - Random packings built of cubes are studied numerically using a random sequential
      adsorption algorithm. To compare the obtained results with previous reports,
      three different models of cube orientation sampling were used. Also, three
      different cube-cube intersection algorithms were tested to find the most
      efficient one. The study focuses on the mean saturated packing fraction as well
      as kinetics of packing growth. Microstructural properties of packings were
      analyzed using density autocorrelation function.

PMID- 29331111
TI  - "Star" morphologies of charged nanodrops comprised of conformational isomers.
AB  - We study the spatial distribution of conformational isomers surrounding a central
      macroion in a charged droplet with linear dimensions in the nanometer range.
      Dimethyl carbonate and formic acid are selected as typical solvents that undergo
      isomerization and a charged buckyball (C60) is selected as a representative
      example of a macroion. The study is performed by atomistic molecular dynamics
      simulations. We find that when the charge of the buckyball is above a threshold
      value, it induces the formation of concentric shells of different conformational
      isomers surrounding the macroion. The presence of layers with different
      dielectric properties necessitates the use of different state equations for the
      solvent polarization in each layer. We find that at a high charge state of the
      buckyball, the nearest layer to the macroion comprises the conformers with the
      highest dipole moment. The interface of the outer layers of conformers is
      characterized by "ray"-forming structures of the higher dielectric constant
      isomers penetrating into the layer of the lowest dielectric constant isomers. For
      high values of the solvent dielectric constant, the charged droplet acquires a
      "star"-like global shape. We demonstrate that these distinct droplet structures
      are a manifestation of charge-induced instability. We describe this simulation
      based phenomenology by an analytical theory that supports this conclusion. The
      findings suggest new experimental research venues that may explore the reactivity
      and assembly of molecules within regions of different dielectric properties in
      droplets.

PMID- 29331112
TI  - Effects of dispersion interactions on the structure, polarity, and dynamics of
      liquid-vapor interface of an aqueous NaCl solution: Results of first principles
      simulations at room temperature.
AB  - The effects of dispersion interaction on the structure, polarity, and dynamics of
      liquid-vapor interface of a concentrated (5.3M) aqueous NaCl solution have been
      investigated through first-principles simulations. Among the structural
      properties, we have investigated the inhomogeneous density profiles of molecules,
      hydrogen bond distributions, and orientational profiles. On the dynamical side,
      we have calculated diffusion, orientational relaxation, hydrogen bond dynamics,
      and vibrational spectral diffusion of molecules. The polarity of water molecules
      across the interface is also calculated. Our simulation results are compared with
      those when no dispersion corrections are included. It is found that the inclusion
      of dispersion correction predicts an overall improvement of the structural
      properties of liquid water. The current study reveals a faster relaxation of
      hydrogen bonds, diffusion, and rotational motion for both interfacial and bulk
      molecules compared to the results when no such dispersion corrections are
      included. The dynamics of vibrational frequency fluctuations are also calculated
      which capture the relaxation of hydrogen bond fluctuations in the bulk and
      interfacial regions. Generally, the hydrogen bonds at the interfaces are found to
      have longer lifetimes due to reduced cooperative effects.

PMID- 29331114
TI  - Hartree-Fock symmetry breaking around conical intersections.
AB  - We study the behavior of Hartree-Fock (HF) solutions in the vicinity of conical
      intersections. These are here understood as regions of a molecular potential
      energy surface characterized by degenerate or nearly degenerate eigenfunctions
      with identical quantum numbers (point group, spin, and electron numbers).
      Accidental degeneracies between states with different quantum numbers are known
      to induce symmetry breaking in HF. The most common closed-shell restricted HF
      instability is related to singlet-triplet spin degeneracies that lead to
      collinear unrestricted HF solutions. Adding geometric frustration to the mix
      usually results in noncollinear generalized HF (GHF) solutions, identified by
      orbitals that are linear combinations of up and down spins. Near conical
      intersections, we observe the appearance of coplanar GHF solutions that break all
      symmetries, including complex conjugation and time-reversal, which do not carry
      good quantum numbers. We discuss several prototypical examples taken from the
      conical intersection literature. Additionally, we utilize a recently introduced
      magnetization diagnostic to characterize these solutions, as well as a solution
      of a Jahn-Teller active geometry of H8+2.

PMID- 29331113
TI  - Uniform magnetic fields in density-functional theory.
AB  - We construct a density-functional formalism adapted to uniform external magnetic
      fields that is intermediate between conventional density functional theory and
      Current-Density Functional Theory (CDFT). In the intermediate theory, which we
      term linear vector potential-DFT (LDFT), the basic variables are the density, the
      canonical momentum, and the paramagnetic contribution to the magnetic moment.
      Both a constrained-search formulation and a convex formulation in terms of
      Legendre-Fenchel transformations are constructed. Many theoretical issues in CDFT
      find simplified analogs in LDFT. We prove results concerning N-representability,
      Hohenberg-Kohn-like mappings, existence of minimizers in the constrained-search
      expression, and a restricted analog to gauge invariance. The issue of additivity
      of the energy over non-interacting subsystems, which is qualitatively different
      in LDFT and CDFT, is also discussed.

PMID- 29331115
TI  - Theoretical analysis of the domain-swapped dimerization of cytochrome c: An MD
      and 3D-RISM approach.
AB  - The structural stability of a cytochrome c domain-swapped dimer compared with
      that of the monomer was investigated by molecular dynamics (MD) simulations and
      by three-dimensional reference interaction site model (3D-RISM) theory. The
      structural fluctuation and structural energy of cytochrome c were treated by MD
      simulations, and the solvation thermodynamics was treated by 3D-RISM theory. The
      domain-swapped dimer state is slightly less stable than the monomer state, which
      is consistent with experimental observations; the total free energy difference is
      calculated as 25 kcal mol-1. The conformational change and
      translational/rotational entropy change contribute to the destabilization of the
      dimer, whereas the hydration and vibrational entropy contribute to the
      stabilization. Further analyses on the residues located at the hinge loop for
      swapping were conducted, and the results reveal details at the molecular level of
      the structural and interaction changes upon dimerization.

PMID- 29331116
TI  - Tensor-decomposed vibrational coupled-cluster theory: Enabling large-scale,
      highly accurate vibrational-structure calculations.
AB  - A new implementation of vibrational coupled-cluster (VCC) theory is presented,
      where all amplitude tensors are represented in the canonical polyadic (CP)
      format. The CP-VCC algorithm solves the non-linear VCC equations without ever
      constructing the amplitudes or error vectors in full dimension but still formally
      includes the full parameter space of the VCC[n] model in question resulting in
      the same vibrational energies as the conventional method. In a previous
      publication, we have described the non-linear-equation solver for CP-VCC
      calculations. In this work, we discuss the general algorithm for evaluating VCC
      error vectors in CP format including the rank-reduction methods used during the
      summation of the many terms in the VCC amplitude equations. Benchmark
      calculations for studying the computational scaling and memory usage of the CP
      VCC algorithm are performed on a set of molecules including thiadiazole and an
      array of polycyclic aromatic hydrocarbons. The results show that the reduced
      scaling and memory requirements of the CP-VCC algorithm allows for performing
      high-order VCC calculations on systems with up to 66 vibrational modes
      (anthracene), which indeed are not possible using the conventional VCC method.
      This paves the way for obtaining highly accurate vibrational spectra and
      properties of larger molecules.

PMID- 29331117
TI  - Accurate virial coefficients of gaseous krypton from state-of-the-art ab initio
      potential and polarizability of the krypton dimer.
AB  - We have developed a new krypton-krypton interaction-induced isotropic dipole
      polarizability curve based on high-level ab initio methods. The determination was
      carried out using the coupled-cluster singles and doubles plus perturbative
      triples method with very large basis sets up to augmented correlation-consistent
      sextuple zeta as well as the corrections for core-core and core-valence
      correlation and relativistic effects. The analytical function of polarizability
      and our recently constructed reference interatomic potential [J. M. Waldrop et
      al., J. Chem. Phys. 142, 204307 (2015)] were used to predict the thermophysical
      and electromagnetic properties of krypton gas. The second pressure, acoustic, and
      dielectric virial coefficients were computed for the temperature range of 116 K
      5000 K using classical statistical mechanics supplemented with high-order quantum
      corrections. The virial coefficients calculated were compared with the generally
      less precise available experimental data as well as with values computed from
      other potentials in the literature {in particular, the recent highly accurate
      potential of Jager et al. [J. Chem. Phys. 144, 114304 (2016)]}. The detailed
      examination in this work suggests that the present theoretical prediction can be
      applied as reference values in disciplines involving thermophysical and
      electromagnetic properties of krypton gas.

PMID- 29331118
TI  - Exploration of near the origin and the asymptotic behaviors of the Kohn-Sham
      kinetic energy density for two-dimensional quantum dot systems with parabolic
      confinement.
AB  - The behaviors of the positive definite Kohn-Sham kinetic energy density near the
      origin and at the asymptotic region play a major role in designing meta
      generalized gradient approximations (meta-GGAs) for exchange in low-dimensional
      quantum systems. It is shown that near the origin of the parabolic quantum dot,
      the Kohn-Sham kinetic energy differs from its von Weizsacker counterpart due to
      the p orbital contributions, whereas in the asymptotic region, the difference
      between the above two kinetic energy densities goes as ~rho(r)r2. All these
      behaviors have been explored using the two-dimensional isotropic quantum harmonic
      oscillator as a test case. Several meta-GGA ingredients are then studied by
      making use of the above findings. Also, the asymptotic conditions for the
      exchange energy density and the potential at the meta-GGA level are proposed
      using the corresponding behaviors of the two kinetic energy densities.

PMID- 29331119
TI  - Molecular dynamics investigation of water-exchange reactions on lanthanide ions
      in water/1-ethyl-3-methylimidazolium trifluoromethylsufate ([EMIm][OTf]).
AB  - We report a kinetic study of the water exchange on lanthanide ions in water/[1
      ethyl-3-methylimidazolium][trifluoromethylsufate] (water/[EMIm][OTf]). The
      results from 17O-NMR measurements show that the water-exchange rates in
      water/[EMIm][OTf] increase with decreasing size of the lanthanide ions. This
      trend for water-exchange is similar to the previously reported trend in water/1
      ethyl-3-methylimidazolium ethyl sulfate (water/[EMIm][EtSO4]) but opposite to
      that in water. To gain atomic-level insight into these water-exchange reactions,
      molecular dynamics simulations for lanthanide ions in water/[EMIm][OTf] have been
      performed using the atomic-multipole-optimized-energetics-for-biomolecular
      application polarizable force field. Our molecular dynamics simulations reproduce
      the experimental water-exchange rates in terms of the trend and provide possible
      explanations for the observed experimental behavior. The smaller lanthanide ions
      in water/[EMIm][OTf] undergo faster water exchange because the smaller lanthanide
      ions coordinate to the first shell [OTf]- anions more tightly, resulting in a
      stronger screening effect for the second-shell water. The screening effect
      weakens the interaction of the lanthanide ions with the second-shell water
      molecules, facilitating the dissociation of water from the second-shell and
      subsequent association of water molecules from the outer solvation shells.

PMID- 29331120
TI  - On the mechanical stability of the body-centered cubic phase and the emergence of
      a metastable cI16 phase in classical hard sphere solids.
AB  - The stability of the body-centered cubic (bcc) solid phase of classical hard
      spheres is of intrinsic interest and is also relevant to the development of
      perturbation theories for bcc solids of other model systems. Using canonical
      ensemble Monte Carlo, we simulated systems initialized in a perfect bcc lattice
      at various densities in the solid region. We observed that the systems rapidly
      evolved into one of four structures that then persisted for the duration of the
      simulation. Remarkably, one of these structures was identified as cI16, a cubic
      crystalline structure with 16 particles in the unit cell, which has recently been
      observed experimentally in lithium and sodium solids at high pressures. The other
      three structures do not exhibit crystalline order but are characterized by common
      patterns in the radial distribution function and bond-orientational order
      parameter distribution; we refer to them as bcc-di, with i ranging from 1 to 3.
      We found similar outcomes when employing any of the three single occupancy cell
      (SOC) restrictions commonly used in the literature. We also ran long constant
      pressure simulations with box shape fluctuations initiated from bcc and cI16
      initial configurations. At lower pressures, all the systems evolved to defective
      face-centered cubic (fcc) or hexagonal close-packed (hcp) structures. At higher
      pressures, most of the systems initiated as bcc evolved to cI16 with some
      evolving to defective fcc/hcp. High pressure systems initiated from cI16 remained
      in that structure. We computed the chemical potential of cI16 using the Einstein
      crystal reference method and found that it is higher than that of fcc by ~0.5kT
      2.5kT over the pressure range studied, with the difference increasing with
      pressure. We find that the undistorted bcc solid, even with constant-volume and
      SOC restrictions applied, is so mechanically unstable that it is unsuitable for
      consideration as a metastable phase or as a reference system for studying bcc
      phases of other systems. On the other hand, cI16 is a mechanically stable
      structure that can spontaneously emerge from a bcc starting point but it is
      thermodynamically metastable relative to fcc or hcp.

PMID- 29331121
TI  - Diffusion of a particle in the spatially correlated exponential random energy
      landscape: Transition from normal to anomalous diffusion.
AB  - Diffusive transport of a particle in a spatially correlated random energy
      landscape having exponential density of states has been considered. We exactly
      calculate the diffusivity in the nondispersive quasi-equilibrium transport regime
      for the 1D transport model and found that for slow decaying correlation functions
      the diffusivity becomes singular at some particular temperature higher than the
      temperature of the transition to the true non-equilibrium dispersive transport
      regime. It means that the diffusion becomes anomalous and does not follow the
      usual ? t1/2 law. In such situation, the fully developed non-equilibrium regime
      emerges in two stages: first, at some temperature there is the transition from
      the normal to anomalous diffusion, and then at lower temperature the average
      velocity for the infinite medium goes to zero, thus indicating the development of
      the true dispersive regime. Validity of the Einstein relation is discussed for
      the situation where the diffusivity does exist. We provide also some arguments in
      favor of conservation of the major features of the new transition scenario in
      higher dimensions.

PMID- 29331122
TI  - Thermally induced charge current through long molecules.
AB  - In this work, we theoretically study steady state thermoelectric transport
      through a single-molecule junction with a long chain-like bridge. Electron
      transmission through the system is computed using a tight-binding model for the
      bridge. We analyze dependences of thermocurrent on the bridge length in unbiased
      and biased systems operating within and beyond the linear response regime. It is
      shown that the length-dependent thermocurrent is controlled by the lineshape of
      electron transmission in the interval corresponding to the HOMO/LUMO transport
      channel. Also, it is demonstrated that electron interactions with molecular
      vibrations may significantly affect the length-dependent thermocurrent.

PMID- 29331123
TI  - The influence of ion hydration on nucleation and growth of LiF crystals in
      aqueous solution.
AB  - Molecular dynamics (MD) simulations are employed to investigate crystal
      nucleation and growth in oversaturated aqueous LiF solutions. Results obtained
      for a range of temperatures provide evidence that the rate of crystal growth is
      determined by a substantial energy barrier (~49 kJ mol-1) related to the loss of
      water from the ion hydration shells. Employing direct MD simulations, we do not
      observe spontaneous nucleation of LiF crystals at 300 K, but nucleation is easily
      observable in NVT simulations at 500 K. This contrasts with the NaCl case, where
      crystal nucleation is directly observed in similar simulations at 300 K. Based on
      these observations, together with a detailed analysis of ion clustering in
      metastable LiF solutions, we argue that the ion dehydration barrier also plays a
      key role in crystal nucleation. The hydration of the relatively small Li+ and F-
      ions strongly influences the probability of forming large, crystal-like ion
      clusters, which are a necessary precursor to nucleation. This important factor is
      not accounted for in classical nucleation theory.

PMID- 29331124
TI  - Characterizing protein conformations by correlation analysis of coarse-grained
      contact matrices.
AB  - We have developed a method to capture the essential conformational dynamics of
      folded biopolymers using statistical analysis of coarse-grained segment-segment
      contacts. Previously, the residue-residue contact analysis of simulation
      trajectories was successfully applied to the detection of conformational
      switching motions in biomolecular complexes. However, the application to large
      protein systems (larger than 1000 amino acid residues) is challenging using the
      description of residue contacts. Also, the residue-based method cannot be used to
      compare proteins with different sequences. To expand the scope of the method, we
      have tested several coarse-graining schemes that group a collection of
      consecutive residues into a segment. The definition of these segments may be
      derived from structural and sequence information, while the interaction strength
      of the coarse-grained segment-segment contacts is a function of the residue
      residue contacts. We then perform covariance calculations on these coarse-grained
      contact matrices. We monitored how well the principal components of the contact
      matrices is preserved using various rendering functions. The new method was
      demonstrated to assist the reduction of the degrees of freedom for describing the
      conformation space, and it potentially allows for the analysis of a system that
      is approximately tenfold larger compared with the corresponding residue contact
      based method. This method can also render a family of similar proteins into the
      same conformational space, and thus can be used to compare the structures of
      proteins with different sequences.

PMID- 29331125
TI  - Diffusion-influenced reaction rates for active "sphere-prolate spheroid" pairs
      and Janus dimers.
AB  - The purpose of this paper is twofold. First, we provide a concise introduction to
      the generalized method of separation of variables for solving diffusion problems
      in canonical domains beyond conventional arrays of spheres. Second, as an
      important example of its application in the theory of diffusion-influenced
      reactions, we present an exact solution of the axially symmetric problem on
      diffusive competition in an array of two active particles (including Janus
      dumbbells) constructed of a prolate spheroid and a sphere. In particular, we
      investigate how the reaction rate depends on sizes of active particles, spheroid
      aspect ratio, particles' surface reactivity, and distance between their centers.

PMID- 29331126
TI  - Binding branched and linear DNA structures: From isolated clusters to fully
      bonded gels.
AB  - The proper design of DNA sequences allows for the formation of well-defined
      supramolecular units with controlled interactions via a consecution of self
      assembling processes. Here, we benefit from the controlled DNA self-assembly to
      experimentally realize particles with well-defined valence, namely, tetravalent
      nanostars (A) and bivalent chains (B). We specifically focus on the case in which
      A particles can only bind to B particles, via appropriately designed sticky-end
      sequences. Hence AA and BB bonds are not allowed. Such a binary mixture system
      reproduces with DNA-based particles the physics of poly-functional condensation,
      with an exquisite control over the bonding process, tuned by the ratio, r,
      between B and A units and by the temperature, T. We report dynamic light
      scattering experiments in a window of Ts ranging from 10  degrees C to 55 
      degrees C and an interval of r around the percolation transition to quantify the
      decay of the density correlation for the different cases. At low T, when all
      possible bonds are formed, the system behaves as a fully bonded network, as a
      percolating gel, and as a cluster fluid depending on the selected r.

PMID- 29331127
TI  - Molecular hydrodynamics: Vortex formation and sound wave propagation.
AB  - In the present study, quantitative feasibility tests of the hydrodynamic
      description of a two-dimensional fluid at the molecular level are performed, both
      with respect to length and time scales. Using high-resolution fluid velocity data
      obtained from extensive molecular dynamics simulations, we computed the
      transverse and longitudinal components of the velocity field by the Helmholtz
      decomposition and compared them with those obtained from the linearized Navier
      Stokes (LNS) equations with time-dependent transport coefficients. By
      investigating the vortex dynamics and the sound wave propagation in terms of
      these field components, we confirm the validity of the LNS description for times
      comparable to or larger than several mean collision times. The LNS description
      still reproduces the transverse velocity field accurately at smaller times, but
      it fails to predict characteristic patterns of molecular origin visible in the
      longitudinal velocity field. Based on these observations, we validate the main
      assumptions of the mode-coupling approach. The assumption that the velocity
      autocorrelation function can be expressed in terms of the fluid velocity field
      and the tagged particle distribution is found to be remarkably accurate even for
      times comparable to or smaller than the mean collision time. This suggests that
      the hydrodynamic-mode description remains valid down to the molecular scale.

PMID- 29331128
TI  - Two-component Gaussian core model: Strong-coupling limit, Bjerrum pairs, and gas
      liquid phase transition.
AB  - In the present work, we investigate a gas-liquid transition in a two-component
      Gaussian core model, where particles of the same species repel and those of
      different species attract. Unlike a similar transition in a one-component system
      with particles having attractive interactions at long separations and repulsive
      interactions at short separations, a transition in the two-component system is
      not driven solely by interactions but by a specific feature of the interactions,
      the correlations. This leads to extremely low critical temperature, as
      correlations are dominant in the strong-coupling limit. By carrying out various
      approximations based on standard liquid-state methods, we show that a gas-liquid
      transition of the two-component system poses a challenging theoretical problem.

PMID- 29331129
TI  - Perspective: Structural fluctuation of protein and Anfinsen's thermodynamic
      hypothesis.
AB  - The thermodynamics hypothesis, casually referred to as "Anfinsen's dogma," is
      described theoretically in terms of a concept of the structural fluctuation of
      protein or the first moment (average structure) and the second moment (variance
      and covariance) of the structural distribution. The new theoretical concept views
      the unfolding and refolding processes of protein as a shift of the structural
      distribution induced by a thermodynamic perturbation, with the variance
      covariance matrix varying. Based on the theoretical concept, a method to
      characterize the mechanism of folding (or unfolding) is proposed. The transition
      state, if any, between two stable states is interpreted as a gap in the
      distribution, which is created due to an extensive reorganization of hydrogen
      bonds among back-bone atoms of protein and with water molecules in the course of
      conformational change. Further perspective to applying the theory to the computer
      aided drug design, and to the material science, is briefly discussed.

PMID- 29331130
TI  - Femtosecond coherent nuclear dynamics of excited tetraphenylethylene: Ultrafast
      transient absorption and ultrafast Raman loss spectroscopic studies.
AB  - Ultrafast torsional dynamics plays an important role in the photoinduced excited
      state dynamics. Tetraphenylethylene (TPE), a model system for the molecular
      motor, executes interesting torsional dynamics upon photoexcitation. The
      photoreaction of TPE involves ultrafast internal conversion via a nearly planar
      intermediate state (relaxed state) that further leads to a twisted zwitterionic
      state. Here, we report the photoinduced structural dynamics of excited TPE during
      the course of photoisomerization in the condensed phase by ultrafast Raman loss
      (URLS) and femtosecond transient absorption (TA) spectroscopy. TA measurements on
      the S1 state reveal step-wise population relaxation from the Franck-Condon (FC)
      state -> relaxed state -> twisted state, while the URLS study provides insights
      on the vibrational dynamics during the course of the reaction. The TA spectral
      dynamics and vibrational Raman amplitudes within 1 ps reveal vibrational wave
      packet propagating from the FC state to the relaxed state. Fourier transformation
      of this oscillation leads to a ~130 cm-1 low-frequency phenyl torsional mode. Two
      vibrational marker bands, Cet=Cet stretching (~1512 cm-1) and Cph=Cph stretching
      (~1584 cm-1) modes, appear immediately after photoexcitation in the URLS spectra.
      The initial red-shift of the Cph=Cph stretching mode with a time constant of ~400
      fs (in butyronitrile) is assigned to the rate of planarization of excited TPE. In
      addition, the Cet=Cet stretching mode shows initial blue-shift within 1 ps
      followed by frequency red-shift, suggesting that on the sub-picosecond time
      scale, structural relaxation is dominated by phenyl torsion rather than the
      central Cet=Cet twist. Furthermore, the effect of the solvent on the structural
      dynamics is discussed in the context of ultrafast nuclear dynamics and solute
      solvent coupling.

PMID- 29331131
TI  - Combining the ensemble and Franck-Condon approaches for calculating spectral
      shapes of molecules in solution.
AB  - The correct treatment of vibronic effects is vital for the modeling of absorption
      spectra of many solvated dyes. Vibronic spectra for small dyes in solution can be
      easily computed within the Franck-Condon approximation using an implicit solvent
      model. However, implicit solvent models neglect specific solute-solvent
      interactions on the electronic excited state. On the other hand, a
      straightforward way to account for solute-solvent interactions and temperature
      dependent broadening is by computing vertical excitation energies obtained from
      an ensemble of solute-solvent conformations. Ensemble approaches usually do not
      account for vibronic transitions and thus often produce spectral shapes in poor
      agreement with experiment. We address these shortcomings by combining zero
      temperature vibronic fine structure with vertical excitations computed for a room
      temperature ensemble of solute-solvent configurations. In this combined approach,
      all temperature-dependent broadening is treated classically through the sampling
      of configurations and quantum mechanical vibronic contributions are included as a
      zero-temperature correction to each vertical transition. In our calculation of
      the vertical excitations, significant regions of the solvent environment are
      treated fully quantum mechanically to account for solute-solvent polarization and
      charge-transfer. For the Franck-Condon calculations, a small amount of frozen
      explicit solvent is considered in order to capture solvent effects on the
      vibronic shape function. We test the proposed method by comparing calculated and
      experimental absorption spectra of Nile red and the green fluorescent protein
      chromophore in polar and non-polar solvents. For systems with strong solute
      solvent interactions, the combined approach yields significant improvements over
      the ensemble approach. For systems with weak to moderate solute-solvent
      interactions, both the high-energy vibronic tail and the width of the spectra are
      in excellent agreement with experiments.

PMID- 29331132
TI  - Detection and characterization of the tin dihydride (SnH2 and SnD2) molecule in
      the gas phase.
AB  - The SnH2 and SnD2 molecules have been detected for the first time in the gas
      phase by laser-induced fluorescence (LIF) and emission spectroscopic techniques
      through the A1B1-X1A1 electronic transition. These reactive species were prepared
      in a pulsed electric discharge jet using (CH3)4Sn or SnH4/SnD4 precursors diluted
      in high pressure argon. Transitions to the electronic excited state of the jet
      cooled molecules were probed with LIF, and the ground state energy levels were
      measured from single rovibronic level emission spectra. The LIF spectrum of SnD2
      afforded sufficient rotational structure to determine the ground and excited
      state geometries: r0" = 1.768 A, theta0" = 91.0 degrees , r0' = 1.729 A, theta0'
      = 122.9 degrees . All of the observed LIF bands show evidence of a rotational
      level-dependent predissociation process which rapidly decreases the fluorescence
      yield and lifetime with increasing rotational angular momentum in each excited
      vibronic level. This behavior is analogous to that observed in SiH2 and GeH2 and
      is suggested to lead to the formation of ground state tin atoms and hydrogen
      molecules.

PMID- 29331133
TI  - The effect of Pd ensemble structure on the O2 dissociation and CO oxidation
      mechanisms on Au-Pd(100) surface alloys.
AB  - The reactivity of various Pd ensembles on the Au-Pd(100) alloy catalyst toward CO
      oxidation was investigated by using density functional theory (DFT). This study
      was prompted by the search for efficient catalysts operating at low temperature
      for the CO oxidation reaction that is of primary environmental importance. To
      this aim, we considered Pd modified Au(100) surfaces including Pd monomers, Pd
      dimers, second neighboring Pd atoms, and Pd chains in a comparative study of the
      minimum energy reaction pathways. The effect of dispersion interactions was
      included in the calculations of the O2 dissociation reaction pathway by using the
      DFT-D3 scheme. The addition of the dispersion interaction strongly improves the
      adsorption ability of O2 on the Au-Pd surface but does not affect the activation
      energy barriers of the Transitions States (TSs). As for O2 to dissociate, it is
      imperative that the TS has lower activation energy than the O2 desorption energy.
      DFT-D3 is found to favor, in some cases, O2 dissociation on configurations being
      identified from uncorrected DFT calculations as inactive. This is the case of the
      second neighboring Pd configuration for which uncorrected DFT predicts positive
      Gibbs free energy (DeltaG) of the O2 adsorption, therefore an endergonic
      reaction. With the addition of D3 correction, DeltaG becomes negative that
      reveals a spontaneous O2 adsorption. Among the investigated Au-Pd (100)
      ensembles, the Pd chain dissociates most easily O2 and highly stabilizes the
      dissociated O atoms; however, it has an inferior reactivity toward CO oxidation
      and CO2 formation. Indeed, CO strongly adsorbs on the palladium bridge sites and
      therefore poisoning the surface Pd chain. By contrast, the second neighboring Pd
      configuration that shows somewhat lower ability to dissociate O2 turns out to be
      more reactive in the CO2 formation step. These results evidence the complex
      effect of Pd ensembles on the CO oxidation reaction. Associative CO oxidation
      proceeds with high energy barriers on all the considered Pd ensembles and should
      be excluded, in agreement with experimental observations.

PMID- 29331134
TI  - Coarse-grained model of nanoscale segregation, water diffusion, and proton
      transport in Nafion membranes.
AB  - We present a coarse-grained model of the acid form of Nafion membrane that
      explicitly includes proton transport. This model is based on a soft-core bead
      representation of the polymer implemented into the dissipative particle dynamics
      (DPD) simulation framework. The proton is introduced as a separate charged bead
      that forms dissociable Morse bonds with water beads. Morse bond formation and
      breakup artificially mimics the Grotthuss hopping mechanism of proton transport.
      The proposed DPD model is parameterized to account for the specifics of the
      conformations and flexibility of the Nafion backbone and sidechains; it treats
      electrostatic interactions in the smeared charge approximation. The simulation
      results qualitatively, and in many respects quantitatively, predict the specifics
      of nanoscale segregation in the hydrated Nafion membrane into hydrophobic and
      hydrophilic subphases, water diffusion, and proton mobility. As the hydration
      level increases, the hydrophilic subphase exhibits a percolation transition from
      a collection of isolated water clusters to a 3D network of pores filled with
      water embedded in the hydrophobic matrix. The segregated morphology is
      characterized in terms of the pore size distribution with the average size
      growing with hydration from ~1 to ~4 nm. Comparison of the predicted water
      diffusivity with the experimental data taken from different sources shows good
      agreement at high and moderate hydration and substantial deviation at low
      hydration, around and below the percolation threshold. This discrepancy is
      attributed to the dynamic percolation effects of formation and rupture of merging
      bridges between the water clusters, which become progressively important at low
      hydration, when the coarse-grained model is unable to mimic the fine structure of
      water network that includes singe molecule bridges. Selected simulations of water
      diffusion are performed for the alkali metal substituted membrane which
      demonstrate the effects of the counter-ions on membrane self-assembly and
      transport. The hydration dependence of the proton diffusivity reproduces semi
      qualitatively the trend of the diverse experimental data, showing a sharp
      decrease around the percolation threshold. Overall, the proposed model opens up
      an opportunity to study self-assembly and water and proton transport in
      polyelectrolytes using computationally efficient DPD simulations, and, with
      further refinement, it may become a practical tool for theory informed design and
      optimization of perm-selective and ion-conducting membranes with improved
      properties.

PMID- 29331135
TI  - Erratum: "Communication: Molecular near-infrared transitions determined with sub
      kHz accuracy" [J. Chem. Phys. 147, 091103 (2017)].

PMID- 29331136
TI  - Zwitterionization of glycine in water environment: Stabilization mechanism and
      NMR spectral signatures.
AB  - At physiological conditions, myriads of biomolecules (e.g., amino acids,
      peptides, and proteins) exist predominantly in the zwitterionic structural form
      and their biological functions will result in these conditions. However these
      geometrical structures are inaccessible energetically in the gas phase, and at
      this point, stabilization of amino-acids in physiological conditions is still
      under debate. In this paper, the electronic properties of a glycine molecule in
      the liquid environment were studied by performing a relaxation of the glycine
      geometry in liquid water using the free energy gradient method combined with a
      sequential quantum mechanics/molecular mechanics approach. A series of Monte
      Carlo Metropolis simulations of the glycine molecule embedded in liquid water,
      followed by only a quantum mechanical calculation in each of them were carried
      out. Both the local and global liquid environments were emphasized to obtain
      nuclear magnetic resonance (NMR) parameters for the glycine molecule in liquid
      water. The results of the equilibrium structure in solution and the systematic
      study of the hydrogen bonds were used to discard the direct proton transfer from
      the carboxyl group to the ammonium group of the glycine molecule in water
      solution. The calculations of the Density Functional Theory (DFT) were performed
      to study the polarization of the solvent in the parameters of nuclear magnetic
      resonance of the glycine molecule in liquid water. DFT calculations predicted
      isotropic chemical changes on the H, C, N, and O atoms of glycine in liquid water
      solution which agree with the available experimental data.

PMID- 29331137
TI  - Molecular dynamics based enhanced sampling of collective variables with very
      large time steps.
AB  - Enhanced sampling techniques that target a set of collective variables and that
      use molecular dynamics as the driving engine have seen widespread application in
      the computational molecular sciences as a means to explore the free-energy
      landscapes of complex systems. The use of molecular dynamics as the fundamental
      driver of the sampling requires the introduction of a time step whose magnitude
      is limited by the fastest motions in a system. While standard multiple time
      stepping methods allow larger time steps to be employed for the slower and
      computationally more expensive forces, the maximum achievable increase in time
      step is limited by resonance phenomena, which inextricably couple fast and slow
      motions. Recently, we introduced deterministic and stochastic resonance-free
      multiple time step algorithms for molecular dynamics that solve this resonance
      problem and allow ten- to twenty-fold gains in the large time step compared to
      standard multiple time step algorithms [P. Minary et al., Phys. Rev. Lett. 93,
      150201 (2004); B. Leimkuhler et al., Mol. Phys. 111, 3579-3594 (2013)]. These
      methods are based on the imposition of isokinetic constraints that couple the
      physical system to Nose-Hoover chains or Nose-Hoover Langevin schemes. In this
      paper, we show how to adapt these methods for collective variable-based enhanced
      sampling techniques, specifically adiabatic free-energy dynamics/temperature
      accelerated molecular dynamics, unified free-energy dynamics, and by extension,
      metadynamics, thus allowing simulations employing these methods to employ
      similarly very large time steps. The combination of resonance-free multiple time
      step integrators with free-energy-based enhanced sampling significantly improves
      the efficiency of conformational exploration.

PMID- 29331139
TI  - Non-iterative triple excitations in equation-of-motion coupled-cluster theory for
      electron attachment with applications to bound and temporary anions.
AB  - The impact of residual electron correlation beyond the equation-of-motion coupled
      cluster singles and doubles (EOM-CCSD) approximation on positions and widths of
      electronic resonances is investigated. To establish a method that accomplishes
      this task in an economical manner, several approaches proposed for the
      approximate treatment of triple excitations are reviewed with respect to their
      performance in the electron attachment (EA) variant of EOM-CC theory. The
      recently introduced EOM-CCSD(T)(a)* method [D. A. Matthews and J. F. Stanton, J.
      Chem. Phys. 145, 124102 (2016)], which includes non-iterative corrections to the
      reference and the target states, reliably reproduces vertical attachment energies
      from EOM-EA-CC calculations with single, double, and full triple excitations in
      contrast to schemes in which non-iterative corrections are applied only to the
      target states. Applications of EOM-EA-CCSD(T)(a)* augmented by a complex
      absorbing potential (CAP) to several temporary anions illustrate that shape
      resonances are well described by EOM-EA-CCSD, but that residual electron
      correlation often makes a non-negligible impact on their positions and widths.
      The positions of Feshbach resonances, on the other hand, are significantly
      improved when going from CAP-EOM-EA-CCSD to CAP-EOM-EA-CCSD(T)(a)*, but the
      correct energetic order of the relevant electronic states is still not achieved.

PMID- 29331138
TI  - Role of non-equilibrium conformations on driven polymer translocation.
AB  - One of the major theoretical methods in understanding polymer translocation
      through a nanopore is the Fokker-Planck formalism based on the assumption of
      quasi-equilibrium of polymer conformations. The criterion for applicability of
      the quasi-equilibrium approximation for polymer translocation is that the average
      translocation time per Kuhn segment, ?tau?/NK, is longer than the relaxation time
      tau0 of the polymer. Toward an understanding of conditions that would satisfy
      this criterion, we have performed coarse-grained three dimensional Langevin
      dynamics and multi-particle collision dynamics simulations. We have studied the
      role of initial conformations of a polyelectrolyte chain (which were artificially
      generated with a flow field) on the kinetics of its translocation across a
      nanopore under the action of an externally applied transmembrane voltage V (in
      the absence of the initial flow field). Stretched (out-of-equilibrium)
      polyelectrolyte chain conformations are deliberately and systematically generated
      and used as initial conformations in translocation simulations. Independent
      simulations are performed to study the relaxation behavior of these stretched
      chains, and a comparison is made between the relaxation time scale and the mean
      translocation time (?tau?). For such artificially stretched initial states,
      ?tau?/NK < tau0, demonstrating the inapplicability of the quasi-equilibrium
      approximation. Nevertheless, we observe a scaling of ?tau? ~ 1/V over the entire
      range of chain stretching studied, in agreement with the predictions of the
      Fokker-Planck model. On the other hand, for realistic situations where the
      initial artificially imposed flow field is absent, a comparison of experimental
      data reported in the literature with the theory of polyelectrolyte dynamics
      reveals that the Zimm relaxation time (tauZimm) is shorter than the mean
      translocation time for several polymers including single stranded DNA (ssDNA),
      double stranded DNA (dsDNA), and synthetic polymers. Even when these data are
      rescaled assuming a constant effective velocity of translocation, it is found
      that for flexible (ssDNA and synthetic) polymers with NK Kuhn segments, the
      condition ?tau?/NK < tauZimm is satisfied. We predict that for flexible polymers
      such as ssDNA, a crossover from quasi-equilibrium to non-equilibrium behavior
      would occur at NK ~ O(1000).

PMID- 29331140
TI  - Erratum: "An automated nudged elastic band method" [J. Chem. Phys. 145, 094107
      (2016)].

PMID- 29331141
TI  - Effects of cross-linking on partitioning of nanoparticles into a polymer brush:
      Coarse-grained simulations test simple approximate theories.
AB  - The effect of cohesive contacts or, equivalently, dynamical cross-linking on the
      equilibrium morphology of a polymer brush infiltrated by nanoparticles that are
      attracted to the polymer strands is studied for plane-grafted brushes using
      coarse-grained molecular dynamics and approximate statistical mechanical models.
      In particular, the Alexander-de Gennes (AdG) and Strong Stretching Theory (SST)
      mean-field theory (MFT) models are considered. It is found that for values of the
      MFT cross-link strength interaction parameter beyond a certain threshold, both
      AdG and SST models predict that the polymer brush will be in a compact state of
      nearly uniform density packed next to the grafting surface over a wide range of
      solution phase nanoparticle concentrations. Coarse grained molecular dynamics
      simulations confirm this prediction, for both small nanoparticles (nanoparticle
      volume = monomer volume) and large nanoparticles (nanoparticle volume = 27 *
      monomer volume). Simulation results for these cross-linked systems are compared
      with analogous results for systems with no cross-linking. At the same solution
      phase nanoparticle concentration, strong cross-linking results in additional
      compression of the brush relative to the non-crosslinked analog and, at all but
      the lowest concentrations, to a lesser degree of infiltration by nanoparticles.
      For large nanoparticles, the monomer density profiles show clear oscillations
      moving outwards from the grafting surface, corresponding to a degree of layering
      of the absorbed nanoparticles in the brush as they pack against the grafting
      surface.

PMID- 29331142
TI  - Kinetic step-growth polymerization: A dissipative particle dynamics simulation
      study.
AB  - Kinetic step-growth polymerization is studied by dissipative particle dynamics
      coupled with our previously developed reaction algorithm on a coarse-grained
      level. The simulation result proves that this step-growth polymerization obeys
      the second-order reaction kinetics. We apply this algorithm to study the step
      growth polymerization using the subunits with different flexibilities or within
      confinement. Good agreement of the number fraction distributions with the Flory
      distribution is obtained, implying that this algorithm is reasonable to describe
      such a kind of step-growth polymerization. This algorithm can further supply a
      convenient platform for simulating typical step-growth polymerization in reactive
      polymer systems.

PMID- 29331143
TI  - Effects of system size and cooling rate on the structure and properties of sodium
      borosilicate glasses from molecular dynamics simulations.
AB  - Borosilicate glasses form an important glass forming system in both glass science
      and technologies. The structure and property changes of borosilicate glasses as a
      function of thermal history in terms of cooling rate during glass formation and
      simulation system sizes used in classical molecular dynamics (MD) simulation were
      investigated with recently developed composition dependent partial charge
      potentials. Short and medium range structural features such as boron
      coordination, Si and B Qn distributions, and ring size distributions were
      analyzed to elucidate the effects of cooling rate and simulation system size on
      these structure features and selected glass properties such as glass transition
      temperature, vibration density of states, and mechanical properties. Neutron
      structure factors, neutron broadened pair distribution functions, and vibrational
      density of states were calculated and compared with results from experiments as
      well as ab initio calculations to validate the structure models. The results
      clearly indicate that both cooling rate and system size play an important role on
      the structures of these glasses, mainly by affecting the 3B and 4B distributions
      and consequently properties of the glasses. It was also found that different
      structure features and properties converge at different sizes or cooling rates;
      thus convergence tests are needed in simulations of the borosilicate glasses
      depending on the targeted properties. The results also shed light on the complex
      thermal history dependence on structure and properties in borosilicate glasses
      and the protocols in MD simulations of these and other glass materials.

PMID- 29331144
TI  - Communication: Site-selective bond excision of adenine upon electron transfer.
AB  - This work demonstrates that selective excision of hydrogen atoms at a particular
      site of the DNA base adenine can be achieved in collisions with electronegative
      atoms by controlling the impact energy. The result is based on analysing the time
      of-flight mass spectra yields of potassium collisions with a series of labeled
      adenine derivatives. The production of dehydrogenated parent anions is consistent
      with neutral H loss either from selective breaking of C-H or N-H bonds. These
      unprecedented results open up a new methodology in charge transfer collisions
      that can initiate selective reactivity as a key process in chemical reactions
      that are dominant in different areas of science and technology.

PMID- 29331145
TI  - Modelling the effect of acoustic waves on the thermodynamics and kinetics of
      phase transformation in a solution: Including mass transportation.
AB  - Effects of acoustic waves on a phase transformation in a metastable phase were
      investigated in our previous work [S. R. Haqshenas, I. J. Ford, and N. Saffari,
      "Modelling the effect of acoustic waves on nucleation," J. Chem. Phys. 145,
      024315 (2016)]. We developed a non-equimolar dividing surface cluster model and
      employed it to determine the thermodynamics and kinetics of crystallisation
      induced by an acoustic field in a mass-conserved system. In the present work, we
      developed a master equation based on a hybrid Szilard-Fokker-Planck model, which
      accounts for mass transportation due to acoustic waves. This model can determine
      the kinetics of nucleation and the early stage of growth of clusters including
      the Ostwald ripening phenomenon. It was solved numerically to calculate the
      kinetics of an isothermal sonocrystallisation process in a system with mass
      transportation. The simulation results show that the effect of mass
      transportation for different excitations depends on the waveform as well as the
      imposed boundary conditions and tends to be noticeable in the case of shock
      waves. The derivations are generic and can be used with any acoustic source and
      waveform.

PMID- 29331146
TI  - Publisher's Note: "The Landau-de Gennes approach revisited: A minimal self
      consistent microscopic theory for spatially inhomogeneous nematic liquid
      crystals" [J. Chem. Phys. 147, 244505 (2017)].

PMID- 29331147
TI  - Direct variational determination of the two-electron reduced density matrix for
      doubly occupied-configuration-interaction wave functions: The influence of three
      index N-representability conditions.
AB  - This work proposes the variational determination of two-electron reduced density
      matrices corresponding to the ground state of N-electron systems within the
      doubly occupied-configuration-interaction methodology. The P, Q, and G two-index
      N-representability conditions have been extended to the T1 and T2 (T2') three
      index ones and the resulting optimization problem has been addressed using a
      standard semidefinite program. We report results obtained from the doubly
      occupied-configuration-interaction method, from the two-index constraint
      variational procedure and from the two- and three-index constraint variational
      treatment. The discussion of these results along with a study of the
      computational cost demanded shows the usefulness of our proposal.

PMID- 29331148
TI  - Isolation of anti-extra-cellular vesicle single-domain antibodies by direct
      panning on vesicle-enriched fractions.
AB  - BACKGROUND: The thorough understanding of the physiological and pathological
      processes mediated by extracellular vesicles (EVs) is challenged by purification
      methods which are cumbersome, not reproducible, or insufficient to yield
      homogeneous material. Chromatography based on both ion-exchange and immune
      capture can represent an effective method to improve EV purification and
      successive analysis. METHODS: Cell culture supernatant was used as a model sample
      for assessing the capacity of anion-exchange chromatography to separate distinct
      EV fractions and to isolate nanobodies by direct panning on whole EVs to recover
      binders specific for the native conformation of EV-surface epitopes and suitable
      to develop EV immune-capture reagents. RESULTS: Anion-exchange chromatography of
      cell culture supernatant separated distinct protein-containing fractions and all
      of them were positive for CD9, a biomarker associated to some EVs. This suggested
      the existence of several EV fractions but did not help in separating EVs from
      other contaminants. We further isolated several nanobodies instrumental for
      implementing immune-affinity protocols. These were able to immobilize EVs from
      both cell culture supernatant and biological samples, to be used in ELISA, flow
      cytometry, and immune-purification. CONCLUSIONS: Here we report the first
      successful isolation of anti-EV nanobodies for the use in immunoaffinity-based EV
      capture by panning a phage library directly on partially purified EVs. This
      achievement paves the way for the application of direct EV panning for the
      discovery of novel antibody-vesicle surface biomarker pairs and represents the
      preliminary requirement for the development of selective immune-capture that, in
      combination with anion-exchange chromatography, can simplify the systematic
      stratification of EV sub-populations and their individual characterization.

PMID- 29331149
TI  - Correction to: Entrapment of an EGFR inhibitor into nanostructured lipid carriers
      (NLC) improves its antitumor activity against human hepatocarcinoma cells.
AB  - Following publication of our article [1], we became aware that Roberto Di Gesu
      had been omitted from the list of authors. The corrected author list and authors'
      contribution statement appear below. We apologize for any inconvenience this may
      have caused.

PMID- 29331150
TI  - Production of eicosapentaenoic acid by application of a delta-6 desaturase with
      the highest ALA catalytic activity in algae.
AB  - : Dunaliella salina is a unicellular green alga with a high alpha-linolenic acid
      (ALA) level, but a low eicosapentaenoic acid (EPA) level. In a previous analysis
      of the catalytic activity of delta 6 fatty acid desaturase (FADS6) from various
      species, FADS6 from Thalassiosira pseudonana (TpFADS6), a marine diatom, showed
      the highest catalytic activity for ALA. In this study, to enhance EPA production
      in D. salina, FADS6 from D. salina (DsFADS6) was identified, and substrate
      specificities for DsFADS6 and TpFADS6 were characterized. Furthermore, a plasmid
      harboring the TpFADS6 gene was constructed and overexpressed in D. salina. Our
      results revealed that EPA production reached 21.3 +/- 1.5 mg/L in D. salina
      transformants. To further increase EPA production, myoinositol (MI) was used as a
      growth-promoting agent; it increased the dry cell weight of D. salina
      transformants, and EPA production reached 91.3 +/- 11.6 mg/L. The combination of
      12% CO2 aeration with glucose/KNO3 in the medium improved EPA production to 192.9
      +/- 25.7 mg/L in the Ds-TpFADS6 transformant. We confirmed that the increase in
      ALA was optimal at 8  degrees C; the EPA percentage reached 41.12 +/- 4.78%. The
      EPA yield was further increased to 554.3 +/- 95.6 mg/L by supplementation with 4
      g/L perilla seed meal (PeSM), 500 mg/L MI, and 12% CO2 aeration with glucose/KNO3
      at varying temperatures. EPA production and the percentage of EPA in D. salina
      were 343.8-fold and 25-fold higher than those in wild-type D. salina,
      respectively. IMPORTANCE: FADS6 from Thalassiosira pseudonana, which demonstrates
      high catalytic activity toward alpha-linolenic acid, was used to enhance EPA
      production by Dunaliella salina. Transformation of FADS6 from Thalassiosira
      pseudonana into Dunaliella salina with myoinositol, CO2, low temperatures, and
      perilla seed meal supplementation substantially increased EPA production in
      Dunaliella salina to 554.3 +/- 95.6 mg/L. Accordingly, D. salina could be a
      potential alternative source of EPA and is suitable for its large-scale
      production.

PMID- 29331151
TI  - The impact of parental mental illness across the full diagnostic spectrum on
      externalising and internalising vulnerabilities in young offspring.
AB  - BACKGROUND: The intergenerational risk for mental illness is well established
      within diagnostic categories, but the risk is unlikely to respect diagnostic
      boundaries and may be reflected more broadly in early life vulnerabilities. We
      aimed to establish patterns of association between externalising and
      internalising vulnerabilities in early childhood and parental mental disorder
      across the full spectrum of diagnoses. METHODS: A cohort of Australian children
      (n = 69 116) entering the first year of school in 2009 were assessed using the
      Australian Early Development Census, providing measures of externalising and
      internalising vulnerability. Parental psychiatric diagnostic status was
      determined utilising record-linkage to administrative health datasets. RESULTS:
      Parental mental illness, across diagnostic categories, was associated with all
      child externalising and internalising domains of vulnerability. There was little
      evidence to support interaction by parental or offspring sex. CONCLUSIONS: These
      findings have important implications for informing early identification and
      intervention strategies in high-risk offspring and for research into the causes
      of mental illness. There may be benefits to focusing less on diagnostic
      categories in both cases.

PMID- 29331152
TI  - Functioning before and after a major depressive episode: pre-existing
      vulnerability or scar? A prospective three-wave population-based study.
AB  - BACKGROUND: The vulnerability hypothesis suggests that impairments after
      remission of depressive episodes reflect a pre-existing vulnerability, while the
      scar hypothesis proposes that depression leaves residual impairments that confer
      risk of subsequent episodes. We prospectively examined vulnerability and scar
      effects in mental and physical functioning in a representative Dutch population
      sample. METHODS: Three waves were used from the Netherlands Mental Health Survey
      and Incidence Study-2, a population-based study with a 6-years follow-up. Mental
      and physical functioning were assessed with the Medical Outcomes Study Short Form
      (SF-36). Major depressive disorder (MDD) was assessed with the Composite
      International Diagnostic Interview 3.0. Vulnerability effects were examined by
      comparing healthy controls (n = 2826) with individuals who developed a first
      onset depressive episode during first follow-up but did not have a lifetime
      diagnosis of MDD at baseline (n = 181). Scarring effects were examined by
      comparing pre- and post-morbid functioning in individuals who developed a
      depressive episode after baseline that was remitted at the third wave (n = 108).
      RESULTS: Both mental (B = -5.4, s.e. = 0.9, p < 0.001) and physical functioning
      (B = -8.2, s.e. = 1.1, p < 0.001) at baseline were lower in individuals who
      developed a first depressive episode after baseline compared with healthy
      controls. This effect was most pronounced in people who developed a severe
      episode. No firm evidence of scarring in mental or physical functioning was
      found. In unadjusted analyses, physical functioning was still lowered post
      morbidly (B = -5.1, s.e. = 2.1, p = 0.014), but this effect disappeared in
      adjusted analyses. CONCLUSIONS: Functional impairments after remission of
      depression seem to reflect a pre-existing vulnerability rather than a scar.

PMID- 29331153
TI  - Is cognitive impairment associated with antipsychotic dose and anticholinergic
      equivalent loads in first-episode psychosis?
AB  - BACKGROUND: Cognitive deficits are a core feature of early stages in
      schizophrenia. However, the extent to which antipsychotic (AP) have a deleterious
      effect on cognitive performance remains under debate. We aim to investigate
      whether anticholinergic loadings and dose of AP drugs in first episode of
      psychosis (FEP) in advanced phase of remission are associated with cognitive
      impairment and the differences between premorbid intellectual quotient (IQ)
      subgroups. METHODS: Two hundred and sixty-six patients participated. The primary
      outcomes were cognitive dimensions, dopaminergic/anticholinergic load of AP [in
      chlorpromazine equivalents (Eq-CPZ) and the Anticholinergic Risk Scale (ARS),
      respectively]. RESULTS: Impairments in processing speed, verbal memory and global
      cognition were significantly associated with high Eq-CPZ and verbal impairment
      with high ARS score. Moreover, this effect was higher in the low IQ subgroup.
      CONCLUSIONS: Clinicians should be aware of the potential cognitive impairment
      associated with AP in advanced remission FEP, particularly in lower premorbid IQ
      patients.

PMID- 29331154
TI  - Predicting Multidrug-Resistant Gram-Negative Bacterial Colonization and
      Associated Infection on Hospital Admission: Methodological Issues.

PMID- 29331155
TI  - Performance of a Novel Antipseudomonal Antibiotic Consumption Metric Among
      Academic Medical Centers in the United States.
AB  - A metric was developed to identify hospital proportion of carbapenem consumption
      (PoCC) among antipseudomonal antibiotics. The PoCC varied significantly among
      academic medical centers by Census Bureau geographic division after adjusting for
      patient mix. This metric may be useful in identifying disproportionate carbapenem
      use and potential carbapenem overuse. Infect Control Hosp Epidemiol 2018;39:229
      232.

PMID- 29331156
TI  - High Hand Contamination Rates During Norovirus Outbreaks in Long-Term Care
      Facilities.
AB  - We examined norovirus contamination on hands of ill patients during 12 norovirus
      outbreaks in 12 long-term care facilities (LTCFs). The higher frequency and
      norovirus titers on hands of residents compared to hands of heathcare workers
      highlights the importance of adhering to appropriate hand hygiene practices
      during norovirus outbreaks in LTCFs. Infect Control Hosp Epidemiol 2018;39:219
      221.

PMID- 29331157
TI  - Eccentric placentae have reduced surface area and are associated with lower birth
      weight in babies small for gestational age.
AB  - Placental structure and function determine birth outcomes. Placental mass does
      not always correlate with fetal birth weight (BW) in uncomplicated pregnancies
      which raises the possibility of other variables such as placental shape and cord
      insertion being the determinants of placental efficiency. In total, 160 women
      with singleton pregnancy, recruited into a pregnancy cohort were studied.
      Placental weight (PW) was measured and other data were obtained from clinical
      records. Birth outcomes were classified as small for gestational age (SGA) and
      appropriate for gestational age (AGA) based on fetal gender, gestational age (GA)
      and BW. High-resolution images of the chorionic plate were recorded. The shape of
      the placenta and the insertion of the cord were measured using eccentricity index
      (EI) and cord centrality index (CCI). Only placentae with eccentrically inserted
      cords (n=136) were included. The mean BW and PW were 2942 (+/-435) g and 414 (+/
      82) g with average GA of 38.6 weeks. The mean CCI and EI was 0.483 (+/-0.17) and
      0.482 (+/-0.16). Neither of these correlated with placental efficiency. However,
      EI showed negative correlation with placental surface area and breadth. Upon sub
      grouping the cohort into SGA (n=32) and AGA (n=104), the SGA babies with the
      highest EI (third tertile) had significantly lower BW than those with the least
      eccentric placentae (first tertile). Although eccentric-shaped placentae were
      present in both SGA and AGA groups, the effect on BW was observed only in the SGA
      group.

PMID- 29331158
TI  - Dietary sources of energy and nutrients in the contemporary diet of Inuit adults:
      results from the 2007-08 Inuit Health Survey.
AB  - OBJECTIVE: To characterize the major components of the contemporary Inuit diet
      and identify the primary sources of energy and essential nutrients. DESIGN:
      Dietary data were derived from the 24 h recall collected by the Inuit Health
      Survey (IHS) from 2007 to 2008. The population proportion method was used to
      determine the percentage contribution of each group. Unique food
      items/preparations (ninety-three country foods and 1591 market foods) were
      classified into eight country food groups and forty-one market food groups.
      Nutrient composition of each food item was obtained from the Canadian Nutrient
      File. SETTING: Thirty-six communities across three Inuit regions of northern
      Canada. SUBJECTS: A representative sample (n 2095) of non-pregnant Inuit adults
      (>=18 years), selected through stratified random sampling. RESULTS: Despite their
      modest contribution to total energy intake (6.4-19.6 %, by region) country foods
      represented a major source of protein (23-52 %), Fe (28-54 %), niacin (24-52 %)
      and vitamins D (up to 73 %), B6 (18-55 %) and B12 (50-82 %). By contrast, the
      three most popular energy-yielding market foods (i.e. sweetened beverages, added
      sugar and bread) collectively contributed approximately 20 % of total energy,
      while contributing minimally to most micronutrients. A notable exception was the
      contribution of these foods to Ca (13-21 %) and vitamins E (17-35 %) and C (as
      much as 50 %). Solid fruits were consumed by less than 25 % of participants while
      vegetables were reported by 38-59 % of respondents. CONCLUSIONS: Country foods
      remain a critical dimension of the contemporary Inuit diet.

PMID- 29331159
TI  - Diagnostic Stewardship for Healthcare-Associated Infections: Opportunities and
      Challenges to Safely Reduce Test Use.

PMID- 29331160
TI  - Reduction in Rate of Nosocomial Respiratory Virus Infections in a Children's
      Hospital Associated With Enhanced Isolation Precautions.
AB  - OBJECTIVE To determine whether the use of enhanced isolation precautions (droplet
      and contact precautions) for inpatients with respiratory tract viral infections
      is associated with a reduction in rate of nosocomial viral respiratory
      infections. DESIGN Quasi-experimental study with the rate of nosocomial
      respiratory virus infection as the primary dependent variable and rate of
      nosocomial Clostridium difficile infection as a nonequivalent dependent variable
      comparator. SETTING Cohen Children's Medical Center of NY, a tertiary-care
      children's hospital attached to a large general hospital. INTERVENTION During
      years 1 and 2 (July 2012 through June 2014), the Centers for Disease Control and
      Prevention/Healthcare Infection Control Practices Advisory Committee's
      recommended isolation precautions for inpatients with selected respiratory virus
      infections were in effect. Enhanced isolation precautions were in effect during
      years 3 and 4 (July, 2014 through June, 2016), except for influenza, for which
      enhanced precautions were in effect during year 4 only. RESULTS During the period
      of enhanced isolation precautions, the rate of nosocomial respiratory virus
      infections with any of 4 virus categories decreased 39% from 0.827 per 1,000
      hospital days prior to enhanced precautions to 0.508 per 1,000 hospital days
      (P<.0013). Excluding rhinovirus/enterovirus infections, the rates decreased 58%
      from 0.317 per 1,000 hospital days to 0.134 per 1,000 hospital days during
      enhanced precautions (P<.0014). During these periods, no significant change was
      detected in the rate of nosocomial C. difficile infection. CONCLUSIONS Enhanced
      isolation precautions for inpatients with respiratory virus infections were
      associated with a reduction in the rate of nosocomial respiratory virus
      infections. Infect Control Hosp Epidemiol 2018;39:152-156.

PMID- 29331161
TI  - Hormone therapy, gender affirmation surgery, and their association with recent
      suicidal ideation and depression symptoms in transgender veterans.
AB  - BACKGROUND: Access to transition-related medical interventions (TRMIs) for
      transgender veterans has been the subject of substantial public interest and
      debate. To better inform these important conversations, the current study
      investigated whether undergoing hormone or surgical transition intervention(s)
      relates to the frequency of recent suicidal ideation (SI) and symptoms of
      depression in transgender veterans. METHODS: This study included a cross
      sectional, national sample of 206 self-identified transgender veterans. They self
      reported basic demographics, TRMI history, recent SI, and symptoms of depression
      through an online survey. RESULTS: Significantly lower levels of SI experienced
      in the past year and 2-weeks were seen in veterans with a history of both hormone
      intervention and surgery on both the chest and genitals in comparison with those
      who endorsed a history of no medical intervention, history of hormone therapy but
      no surgical intervention, and those with a history of hormone therapy and surgery
      on either (but not both) the chest or genitals when controlling for sample
      demographics (e.g., gender identity and annual income). Indirect effect analyses
      indicated that lower depressive symptoms experienced in the last 2-weeks mediated
      the relationship between the history of surgery on both chest and genitals and SI
      in the last 2-weeks. CONCLUSIONS: Results indicate the potential protective
      effect that TRMI may have on symptoms of depression and SI in transgender
      veterans, particularly when both genitals and chest are affirmed with one's
      gender identity. Implications for policymakers, providers, and researchers are
      discussed.

PMID- 29331162
TI  - Unnecessary Removal of Central Venous Catheters in Cancer Patients with
      Bloodstream Infections.
AB  - We evaluated the rate of central venous catheter (CVC) removal in 283 cancer
      patients with bloodstream infections (BSIs). Removal of CVCs occurred
      unnecessarily in 57% of patients with non-central-line-associated BSI (non
      CLABSI), which was equivalent to the rate of CVC removal in patients with
      CLABSIs. Physician education and safe interventions to salvage the vascular
      access are warranted. Infect Control Hosp Epidemiol 2018;39:222-225.

PMID- 29331163
TI  - Healthcare Personnel Relationships Related to Coordination of Catheter Care.

PMID- 29331164
TI  - Adherence to the Danish food-based dietary guidelines and risk of myocardial
      infarction: a cohort study.
AB  - OBJECTIVE: A direct way to evaluate food-based dietary guidelines is to assess if
      adherence is associated with development of non-communicable diseases. Thus, the
      objective was to develop an index to assess adherence to the 2013 Danish food
      based dietary guidelines and to investigate the association between adherence to
      the index and risk of myocardial infarction (MI). DESIGN: Population-based cohort
      study with recruitment of participants in 1993-1997. Information on dietary
      intake was collected at baseline using an FFQ and an index ranging from 0 to 6
      points was created to assess adherence to the 2013 Danish food-based dietary
      guidelines. MI cases were identified by record linkage to the Danish National
      Patient Register and the Causes of Death Register. Cox proportional hazards
      models were used to estimate hazard ratios (HR) of MI. SETTING: Greater areas of
      Aarhus and Copenhagen, Denmark. SUBJECTS: Men and women aged 50-64 years (n 55
      021) from the Diet, Cancer and Health study. RESULTS: A total of 3046
      participants were diagnosed with first-time MI during a median follow-up of 16.9
      years. A higher Danish Dietary Guidelines Index score was associated with a lower
      risk of MI. After adjustment for potential confounders, the hazard of MI was 13 %
      lower among men with a score of 3-<4 (HR=0.87; 95 % CI 0.78, 0.96) compared with
      men with a score of <3. The corresponding HR among women was 0.76 (95 % CI 0.63,
      0.93). CONCLUSIONS: Adherence to the 2013 Danish food-based dietary guidelines
      was inversely associated with risk of MI.

PMID- 29331165
TI  - Investigating the population structure and genetic differentiation of livestock
      guard dog breeds.
AB  - Livestock guarding dogs are a valuable adjunct to the pastoral community. Having
      been traditionally selected for their working ability, they fulfil their function
      with minimal interaction or command from their human owners. In this study, the
      population structure and the genetic differentiation of three Italian livestock
      guardian breeds (Sila's Dog, Maremma and Abruzzese Sheepdog and Mannara's Dog)
      and three functionally and physically similar breeds (Cane Corso, Central Asian
      Shepherd Dog and Caucasian Shepherd Dog), totalling 179 dogs unrelated at the
      second generation, were investigated with 18 autosomal microsatellite markers.
      Values for the number of alleles per locus, observed and expected heterozygosity,
      Hardy-Weinberg Equilibrium, F stats, Nei's and Reynold's genetic distances,
      clustering and sub-population formation abilities and individual genetic
      structures were calculated. Our results show clear breed differentiation, whereby
      all the considered breeds show reasonable genetic variability despite small
      population sizes and variable selection schemes. These results provide meaningful
      data to stakeholders in specific breed and environmental conservation programmes.

PMID- 29331166
TI  - Institution-wide and Within-Patient Evolution of Daptomycin Susceptibility in
      Vancomycin-Resistant Enterococcus faecium Bloodstream Infections.
AB  - We report daptomycin minimum inhibitory concentrations (MICs) for vancomycin
      resistant Enterococcus faecium isolated from bloodstream infections over a 4-year
      period. The daptomycin MIC increased over time hospital-wide for initial isolates
      and increased over time within patients, culminating in 40% of patients having
      daptomycin-nonsusceptible isolates in the final year of the study. Infect Control
      Hosp Epidemiol 2018;39:226-228.

PMID- 29331167
TI  - The association between psychotic experiences and traumatic life events: the role
      of the intention to harm.
AB  - BACKGROUND: Previous work showed traumatic life events (TLE) with intention to
      harm, like bullying and abuse, to be more strongly associated with psychotic
      experiences (PE) than other types of trauma, like accidents. However, this
      association is subject to reporting bias and can be confounded by demographic
      characteristics and by differences in dose of exposure across different trauma
      categories. We studied the association between TLE with and without intention to
      harm and PE, taking into account potential confounders and biases. METHODS: A
      total of 2245 children and adolescents aged 6-14 years were interviewed by
      psychologists. The interview included the presence of 20 PE (both self-report and
      psychologist evaluation). In addition, parents provided information on child
      exposure to trauma, mental health and PE. RESULTS: Results showed no significant
      association between TLE without intention to harm only and PE for the three
      methods of assessment of PE (self-report, parent report and psychologist rating).
      On the other hand, there was a positive association between PE and TLE in groups
      exposed to traumatic experiences with intention to harm (with intention to harm
      only and with and without intention to harm). Results remained significant after
      controlling for demographic and clinical confounders, but this positive
      association was no longer significant after adjusting for the number of TLE.
      CONCLUSIONS: TLE with intention to harm display a stronger association with PE
      than TLE without intention to harm, and this difference is likely reducible to a
      greater level of traumatic exposure associated with TLE with intention to harm.

PMID- 29331168
TI  - Dietary patterns and their associations with home food availability among Finnish
      pre-school children: a cross-sectional study.
AB  - OBJECTIVE: To study the associations between home food availability and dietary
      patterns among pre-school children. DESIGN: Cross-sectional study in which
      parents of the participating children filled in an FFQ and reported how often
      they had certain foods in their homes. We derived dietary pattern scores using
      principal component analysis, and composite scores describing the availability of
      fruits and vegetables as well as sugar-enriched foods in the home were created
      for each participant. We used multilevel models to investigate the associations
      between availability and dietary pattern scores. SETTING: The DAGIS study,
      Finland. SUBJECTS: The participants were 864 Finnish 3-6-year-old children
      recruited from sixty-six pre-schools. The analyses included 711 children with
      sufficient data. RESULTS: We identified three dietary patterns explaining 16.7 %
      of the variance. The patterns were named 'sweets-and-treats' (high loadings of
      e.g. sweet biscuits, chocolate, ice cream), 'health-conscious' (high loadings of
      e.g. nuts, natural yoghurt, berries) and 'vegetables-and-processed meats' (high
      loadings of e.g. vegetables, cold cuts, fruit). In multivariate models, the
      availability of fruits and vegetables was inversely associated with the sweets
      and-treats pattern (beta=-0.05, P<0.01) and positively associated with the health
      conscious (beta=0.07, P<0.01) and vegetables-and-processed meats patterns
      (beta=0.06, P<0.01). The availability of sugar-enriched foods was positively
      associated with the sweets-and-treats pattern (beta=0.10, P<0.01) and inversely
      associated with the health-conscious pattern (beta=-0.03, P<0.01). CONCLUSIONS:
      Considering dietary patterns, the availability of sugar-enriched foods in the
      home seems to have a stronger role than that of fruits and vegetables. Parents
      should restrict the availability of unhealthy foods in the home.

PMID- 29331169
TI  - The introduction of simple cardiorespiratory fitness testing in overweight/obese
      type 2 diabetics: a pilot study.
AB  - BACKGROUND: Low level of cardiorespiratory fitness has been recognized as an
      important independent and modifiable risk factor of increased morbidity and
      mortality. However, in standard outpatient settings, patients are not routinely
      screened for fitness and advantages of such testing for the management of type 2
      diabetes have not been defined.AimTo describe the toleration of a fast, simple
      and practicable fitness test (2-min step-in-place test) by overweight/obese type
      2 diabetics and their performance indicated by 2-min step-in-place test score
      (STS). To study short-term anthropometric, functional and metabolic changes
      following the implementation of the test in the selected population. METHODS: A
      total of 33 overweight/obese type 2 diabetics underwent, besides routine
      examination at the outpatient clinic, the fitness test (group A). Patients were
      asked to increase their regular physical activity with focus on walking without
      change in diet and chronic medication. Three to four months later, the subjects
      were tested again. An identical number of age- and sex-matched obese diabetics
      followed in our outpatient clinic (without fitness testing), was randomly
      selected from the Hospital Information System (control group B).FindingsAll
      patients subjected to fitness testing completed the protocol successfully. STS
      score was found to have a considerable range with differences between males and
      females at the borderline of statistical significance. The data are compliant
      with lower aerobic endurance of obese diabetics compared with healthy population.
      Within study period, the tested group presented with improvements in STS
      (referring especially to the males) as well as in several laboratory parameters
      of glucose and lipid homeostasis, glomerular function and subclinical
      inflammation with no reflection in anthropometry. Group B demonstrated no
      significant change. In conclusion, 2-min step-in-place test is fast, undemanding
      and well-tolerated by patients and personnel. Following its validation based on
      cardiopulmonary exercise testing, the test may prove recommendable for screening
      or self-monitoring purposes.

PMID- 29331170
TI  - Implementation Lessons Learned From the Benefits of Enhanced Terminal Room (BETR)
      Disinfection Study: Process and Perceptions of Enhanced Disinfection with
      Ultraviolet Disinfection Devices.
AB  - OBJECTIVE To summarize and discuss logistic and administrative challenges we
      encountered during the Benefits of Enhanced Terminal Room (BETR) Disinfection
      Study and lessons learned that are pertinent to future utilization of ultraviolet
      (UV) disinfection devices in other hospitals DESIGN Multicenter cluster
      randomized trial SETTING AND PARTICIPANTS Nine hospitals in the southeastern
      United States METHODS All participating hospitals developed systems to implement
      4 different strategies for terminal room disinfection. We measured compliance
      with disinfection strategy, barriers to implementation, and perceptions from
      nurse managers and environmental services (EVS) supervisors throughout the 28
      month trial. RESULTS Implementation of enhanced terminal disinfection with UV
      disinfection devices provides unique challenges, including time pressures from
      bed control personnel, efficient room identification, negative perceptions from
      nurse managers, and discharge volume. In the course of the BETR Disinfection
      Study, we utilized several strategies to overcome these barriers: (1)
      establishing safety as the priority; (2) improving communication between EVS, bed
      control, and hospital administration; (3) ensuring availability of necessary
      resources; and (4) tracking and providing feedback on compliance. Using these
      strategies, we deployed ultraviolet (UV) disinfection devices in 16,220 (88%) of
      18,411 eligible rooms during our trial (median per hospital, 89%; IQR, 86%-92%).
      CONCLUSIONS Implementation of enhanced terminal room disinfection strategies
      using UV devices requires recognition and mitigation of 2 key barriers: (1)
      timely and accurate identification of rooms that would benefit from enhanced
      terminal disinfection and (2) overcoming time constraints to allow EVS cleaning
      staff sufficient time to properly employ enhanced terminal disinfection methods.
      TRIAL REGISTRATION Clinical trials identifier: NCT01579370 Infect Control Hosp
      Epidemiol 2018;39:157-163.

PMID- 29331173
TI  - Editorial.

PMID- 29331174
TI  - Transcatheter tricuspid repair: The knifeless cutting edge.

PMID- 29331171
TI  - The genotypic and phenotypic spectrum of MTO1 deficiency.
AB  - BACKGROUND: Mitochondrial diseases, a group of multi-systemic disorders often
      characterized by tissue-specific phenotypes, are usually progressive and fatal
      disorders resulting from defects in oxidative phosphorylation. MTO1
      (Mitochondrial tRNA Translation Optimization 1), an evolutionarily conserved
      protein expressed in high-energy demand tissues has been linked to human early
      onset combined oxidative phosphorylation deficiency associated with hypertrophic
      cardiomyopathy, often referred to as combined oxidative phosphorylation
      deficiency-10 (COXPD10). MATERIAL AND METHODS: Thirty five cases of MTO1
      deficiency were identified and reviewed through international collaboration. The
      cases of two female siblings, who presented at 1 and 2years of life with
      seizures, global developmental delay, hypotonia, elevated lactate and complex I
      and IV deficiency on muscle biopsy but without cardiomyopathy, are presented in
      detail. RESULTS: For the description of phenotypic features, the denominator
      varies as the literature was insufficient to allow for complete ascertainment of
      all data for the 35 cases. An extensive review of all known MTO1 deficiency cases
      revealed the most common features at presentation to be lactic acidosis (LA)
      (21/34; 62% cases) and hypertrophic cardiomyopathy (15/34; 44% cases). Eventually
      lactic acidosis and hypertrophic cardiomyopathy are described in 35/35 (100%) and
      27/34 (79%) of patients with MTO1 deficiency, respectively; with global
      developmental delay/intellectual disability present in 28/29 (97%), feeding
      difficulties in 17/35 (49%), failure to thrive in 12/35 (34%), seizures in 12/35
      (34%), optic atrophy in 11/21 (52%) and ataxia in 7/34 (21%). There are 19
      different pathogenic MTO1 variants identified in these 35 cases: one splice-site,
      3 frameshift and 15 missense variants. None have bi-allelic variants that
      completely inactivate MTO1; however, patients where one variant is truncating
      (i.e. frameshift) while the second one is a missense appear to have a more
      severe, even fatal, phenotype. These data suggest that complete loss of MTO1 is
      not viable. A ketogenic diet may have exerted a favourable effect on seizures in
      2/5 patients. CONCLUSION: MTO1 deficiency is lethal in some but not all cases,
      and a genotype-phenotype relation is suggested. Aside from lactic acidosis and
      cardiomyopathy, developmental delay and other phenotypic features affecting
      multiple organ systems are often present in these patients, suggesting a broader
      spectrum than hitherto reported. The diagnosis should be suspected on clinical
      features and the presence of markers of mitochondrial dysfunction in body fluids,
      especially low residual complex I, III and IV activity in muscle. Molecular
      confirmation is required and targeted genomic testing may be the most efficient
      approach. Although subjective clinical improvement was observed in a small number
      of patients on therapies such as ketogenic diet and dichloroacetate, no evidence
      based effective therapy exists.

PMID- 29331172
TI  - Blood phenylalanine reduction corrects CNS dopamine and serotonin deficiencies
      and partially improves behavioral performance in adult phenylketonuric mice.
AB  - Central nervous system (CNS) deficiencies of the monoamine neurotransmitters
      dopamine and serotonin have been implicated in the pathophysiology of
      neuropsychiatric dysfunction in human phenylketonuria (PKU). In this study, we
      confirmed the occurrence of brain dopamine and serotonin deficiencies in
      association with severe behavioral alterations and cognitive impairments in
      hyperphenylalaninemic C57BL/6-Pahenu2/enu2 mice, a model of human PKU.
      Phenylalanine-reducing treatments, including either dietary phenylalanine
      restriction or liver-directed gene therapy, initiated during adulthood were
      associated with increased brain monoamine content along with improvements in
      nesting behavior but without a change in the severe cognitive deficits exhibited
      by these mice. At euthanasia, there was in Pahenu2/enu2 brain a significant
      reduction in the protein abundance and maximally stimulated activities of
      tyrosine hydroxylase (TH) and tryptophan hydroxylase 2 (TPH2), the rate limiting
      enzymes catalyzing neuronal dopamine and serotonin synthesis respectively, in
      comparison to levels seen in wild type brain. Phenylalanine-reducing treatments
      initiated during adulthood did not affect brain TH or TPH2 content or maximal
      activity. Despite this apparent fixed deficit in striatal TH and TPH2 activities,
      initiation of phenylalanine-reducing treatments yielded substantial correction of
      brain monoamine neurotransmitter content, suggesting that phenylalanine-mediated
      competitive inhibition of already constitutively reduced TH and TPH2 activities
      is the primary cause of brain monoamine deficiency in Pahenu2 mouse brain. We
      propose that CNS monoamine deficiency may be the cause of the partially
      reversible adverse behavioral effects associated with chronic HPA in Pahenu2
      mice, but that phenylalanine-reducing treatments initiated during adulthood are
      unable to correct the neuropathology and attendant cognitive deficits that
      develop during juvenile life in late-treated Pahenu2/enu2 mice.

PMID- 29331175
TI  - TRACERx: Tracking tumor evolution to impact the course of lung cancer.

PMID- 29331176
TI  - Fontan outcomes: Is being educated as good as being wealthy and healthy?

PMID- 29331177
TI  - Trans-diaphragmatic chest surgery: Bringing owls to Athens?

PMID- 29331178
TI  - Multiple mechanical support modalities and cardiac transplantation in a young
      child with corrected transposition.

PMID- 29331179
TI  - Surprises happen all the time.

PMID- 29331180
TI  - Oh, father, where art we? Left internal mammary artery with greater saphenous
      vein grafts still rules surgical coronary revascularization after 30 years.

PMID- 29331181
TI  - Play it again...Dr Gibbon.

PMID- 29331182
TI  - The long and winding route.

PMID- 29331183
TI  - ?

PMID- 29331185
TI  - [Patients and caregivers in the treatment of addictions].
AB  - Since the 1980s, risk and harm reduction has been a public health issue in the
      area of addictions. A new approach has been adopted with drug users, who are
      considered as patients like any other and players in their own health care. The
      therapeutic alliance with the caregiver is therefore essential.

PMID- 29331184
TI  - ?

PMID- 29331186
TI  - [Addictology, promoting users' power to act].
AB  - The notion of risk reduction applies to all uses, drinking of alcohol and smoking
      including, addictions without drugs likewise. With regard to drugs, mentalities
      change. We now talk more of risks than fault or deviance. Following,
      collaboration between health professionals and users, sharing and cooperation are
      the conditions necessary to develop a modern humanist and social addictology
      approach.

PMID- 29331187
TI  - [Nursing role and risk reduction for drug users].
AB  - The Ithaque association is a drop-in and risk reduction centre for drug users. It
      caters for anyone 'overwhelmed' by an addiction with a view to supporting them in
      the treatment approach they wish to undertake. Nurses play a key role throughout
      the user's care pathway.

PMID- 29331188
TI  - [Care pathway and life course of drug-addicted patients].
AB  - Placing drug addicts, notably heroin addicts, at the centre of their care
      project, itself part of a life project, is the objective of the Le Lac d'Argent
      association in Annecy. Caregivers have been able to reflect on their practices
      and help to fight against preconceived ideas. This article presents the
      experience of a global support approach.

PMID- 29331189
TI  - [Day clinic, a gateway towards risk reduction].
AB  - The addictology day clinic at Fernand-Widal hospital in Paris caters mainly for
      patients suffering from alcohol dependence. The aim is to consolidate the
      withdrawal which has taken place, to help reduce risks and harm and to support
      people waiting for follow-up care.

PMID- 29331190
TI  - ?

PMID- 29331191
TI  - [An innovative teleconsultation project in liver transplantation].
AB  - The Tours and Bourges hospital teams have developed innovative collaborative
      practices in the monitoring of patients having received a liver transplant.
      Teleconsultation helps the patient resume their normal life by enabling them to
      avoid tiring and time-consuming appointments.

PMID- 29331192
TI  - [Psychiatry and palliative care, collaboration for the benefit of the patient].
AB  - As palliative care units continue to develop, the provision of end-of-life care
      for patients with a chronic mental illness needs to be addressed. Aside from the
      somatic comorbidities to which these patients are particularly exposed and in
      view of the specificity of psychiatric treatment, the forms of end-of-life
      support for a patient with schizophrenia are described here, based on the
      experience of a psychiatric unit in the Var region.

PMID- 29331193
TI  - [Using connected objects to favour patients' adherence to physical activity].
AB  - A study explored the factors which can have an impact on the use of connected
      objects to improve patients' adherence to physical activity, when they suffer
      from chronic low back pain. The results can be used to adjust the development of
      an application aimed at patients with chronic low back pain.

PMID- 29331194
TI  - [Specificities of nursing care in neurological intensive care].
AB  - In the acute phase of the treatment of patients with brain injuries, the
      management of secondary brain injuries of systemic origin is a priority. A
      neurosurgical intensive care paramedical team shares their experience of the care
      delivered and the constant monitoring carried out to optimise, with the medical
      team, the patient's outcome and to innovate practices.

PMID- 29331195
TI  - [Educational project for raising awareness of food hygiene in infant schools].
AB  - Five students from a nursing training institute designed an educational
      initiative aimed at infant school pupils. The objective of this primary
      prevention intervention was to raise children's awareness of food hygiene.

PMID- 29331196
TI  - ?

PMID- 29331197
TI  - Talking about the Impact of Screen-viewing on Health.
AB  - Emilia is a young woman admitted to the hospital for pyelonephritis. Sophie finds
      out, from the morning reports about her, that she stays awake very late every
      night watching television or chatting on her mobile phone.

PMID- 29331198
TI  - ?

PMID- 29331199
TI  - ?

PMID- 29331200
TI  - Saliency modulates affective evaluations but not behavioral responses in the
      ultimatum game.
AB  - Although numerous studies have demonstrated that the saliency of perceptual
      information guides attention, the effect of perceptual saliency in high-level
      social situations remains unclear. Here, in a modified ultimatum game that
      included both gain and loss sharing, we highlighted either the fairness (fair or
      unfair) or the valence (gain or loss) aspect of a proposed offer using salient
      background colors with social meanings. The results showed that emotional
      responses to proposed offers were influenced by visual saliency. Specifically,
      individuals felt more dissatisfied about unfair (as opposed to fair) offers when
      fairness was emphasized than when valence was emphasized or no emphasis; and
      similarly, individuals felt more dissatisfied about loss situations compared to
      gain situations when valence was emphasized than when fairness was emphasized or
      no emphasis. However, this attentional modulation of social information led to
      changes only on affective responses but not on actual behavioral responses. Our
      findings indicate that attentional modulation of social information has a
      profound impact on affective evaluation by changing how information is weighed.

PMID- 29331201
TI  - Impact of polymer geometry on the interactions of protein-PEG conjugates.
AB  - The conjugation of high molecular weight polyethylene glycol (PEG) to an active
      pharmaceutical ingredient (API) is an attractive strategy for the modification of
      biophysical and biodistribution properties of the API. Indeed, several
      therapeutic proteins conjugated to PEG have been safely administered in the
      clinic. While there have been studies on the configuration of these conjugates in
      solution, investigations on the impact of PEG geometry on protein-PEG conjugate
      interactions is limited. In this study, we use dynamic light scattering (DLS),
      rheology, and small-angle neutron scattering (SANS) to investigate the
      biophysical solution and interaction behavior of a 50kDa Fab protein attached to
      either a linear or tetrameric (branched) 40kDa PEG molecule. The hydrodynamic
      radii, diffusivity, viscosity and pair distance distribution function (PDDF) were
      obtained for the protein-PEG conjugates in solution. An analysis revealed that
      interactions between unconjugated proteins were quite attractive, however linear
      PEG-protein conjugates exhibited net repulsive interactions, similar to that of
      the unconjugated polymer. Tetramer PEG-protein conjugates on the other hand,
      exhibited a net weak attractive interaction, indicating a more balanced
      distribution of repulsive and attractive interaction states. Further analysis of
      the SANS data using geometric models consistent with the PDDF elucidated the
      conjugates' equilibrium configuration in solution. Insights gained from
      measurements and analysis used here can also be useful in predicting how
      conjugate geometries affect viscosity and aggregation behavior, which are
      important in determining suitable protein-polymer drug formulations.

PMID- 29331202
TI  - New anesthetic considerations in thoracic surgery.

PMID- 29331203
TI  - Have we forgotten about forgetting? A critical review of 'accelerated long-term
      forgetting' in temporal lobe epilepsy.
AB  - Forgetting has been researched for over a century. This literature highlighted
      how forgetting rates can vary dependent on factors in the design and method.
      Recent interest in forgetting revived with evidence suggesting that seizures
      experienced almost immediately after matched learning could accelerate
      forgetting. This was followed by a growth in forgetting studies in patients with
      temporal lobe epilepsy (TLE), including a subset of those with transient
      epileptic amnesia (TEA). These patients have been described as expressing
      concerns about memory, yet often perform within 'normal' ranges on standard
      neuropsychological memory assessments. It was argued that such patients were
      experiencing a phenomenon termed 'accelerated long-term forgetting': apparently
      normal learning and initial retention with abnormal forgetting over days to weeks
      after learning. In this review, we critically evaluate aspects of this
      definition, namely whether learning and initial retention is, in fact, 'normal'
      at first, and further what this means in relation to 'when' abnormal forgetting
      starts. We propose a shift in the understanding of accelerated forgetting in TLE
      from an emphasis on late-onset forgetting to greater focus on early-onset,
      progressively greater forgetting. We argue that most evidence from studies to
      date could be conceptualized within the latter framework, with differences in
      forgetting patterns reflective of a continuum of severity and/or sensitivity.

PMID- 29331204
TI  - A cognitive model for multidigit number reading: Inferences from individuals with
      selective impairments.
AB  - We propose a detailed cognitive model of multi-digit number reading. The model
      postulates separate processes for visual analysis of the digit string and for
      oral production of the verbal number. Within visual analysis, separate sub
      processes encode the digit identities and the digit order, and additional sub
      processes encode the number's decimal structure: its length, the positions of 0,
      and the way it is parsed into triplets (e.g., 314987 -> 314,987). Verbal
      production consists of a process that generates the verbal structure of the
      number, and another process that retrieves the phonological forms of each number
      word. The verbal number structure is first encoded in a tree-like structure,
      similarly to syntactic trees of sentences, and then linearized to a sequence of
      number-word specifiers. This model is based on an investigation of the number
      processing abilities of seven individuals with different selective deficits in
      number reading. We report participants with impairment in specific sub-processes
      of the visual analysis of digit strings - in encoding the digit order, in
      encoding the number length, or in parsing the digit string to triplets. Other
      participants were impaired in verbal production, making errors in the number
      structure (shifts of digits to another decimal position, e.g., 3,040 -> 30,004).
      Their selective deficits yielded several dissociations: first, we found a double
      dissociation between visual analysis deficits and verbal production deficits.
      Second, several dissociations were found within visual analysis: a double
      dissociation between errors in digit order and errors in the number length; a
      dissociation between order/length errors and errors in parsing the digit string
      into triplets; and a dissociation between the processing of different digits -
      impaired order encoding of the digits 2-9, without errors in the 0 position.
      Third, within verbal production, a dissociation was found between digit shifts
      and substitutions of number words. A selective deficit in any of the processes
      described by the model would cause difficulties in number reading, which we
      propose to term "dysnumeria".

PMID- 29331205
TI  - Free thyroxine and TSH interact with secreted protein acidic and rich in cysteine
      like 1 in ischemic stroke.
AB  - The role of the thyroid gland in ischemic stroke pathology is not well
      understood. As thyroid hormones modulate the extracellular matrix, we explored
      the possible link between them and secreted protein acidic and rich in cysteine
      like 1 (SC1) - one of the extracellular matrix molecules. In the 81 patients with
      acute ischemic stroke, serum SC1 levels were much higher compared with 30 control
      subjects: 4.47 vs 2.43ng/mL (p<0.001). Serum levels of free thyroxine (fT4) were
      higher in stroke subjects compared to those of controls (p=0.03). In stroke
      patients, TSH concentration was lower than in the control group (p=0.03). SC1
      levels positively correlated with fT4 levels (p=0.02) and negatively with TSH
      (p=0.03) in stroke patients. Our results confirmed the association between
      thyroid hormones and SC1 - extracellular matrix protein.

PMID- 29331206
TI  - Mechanical thrombectomy: Determining the proportion of eligible acute ischemic
      stroke patients in the cohort of single academic stroke center.
AB  - BACKGROUND AND PURPOSE: Mechanical thrombectomy (MT) is now well-established
      treatment method for selected patients with acute ischemic stroke (AIS) and
      efforts are being made to incorporate it into the systems of stroke care. Our
      objective is to assess the number of AIS individuals eligible for MT in the
      cohort of single academic stroke center. METHODS: We retrospectively reviewed
      initial non-invasive vascular imaging data of AIS patients presenting within 5h
      of symptom onset for the presence of large vessel occlusion (LVO) over 2-year
      period (2015-2016). Among subjects confirmed with LVO: time-to-presentation,
      premorbid functional and on-admission neurological state, site of occlusion and
      initial imaging data were further assessed. Two sets of criteria based on recent
      trials and recommendations were used to determine MT eligibility. The onset-to
      evaluation time limit was set to 5h allowing <=60min procedure initiation delay.
      RESULTS: 895 patients with the final diagnosis of AIS were admitted to our stroke
      center as the initial treatment facility. 246 (27.5%) presented within 5h of
      symptom onset and had non-invasive imaging performed. Among those 102 (41.5%) had
      causative LVO. The number of <=5h presenting patients eligible for MT was 51
      (20.7%) when applying restrictive or 80 (32.5%) with more permissive criteria.
      CONCLUSION: Among AIS patients, in whom onset-to-arrival time allowed to initiate
      the endovascular procedure within 6h of symptom duration, 21% were eligible for
      MT treatment according to more and 33% to less restrictive criteria. It accounts
      for about 6% and 9% of all AIS cases, respectively.

PMID- 29331207
TI  - Cerebral amyloid angiopathy-related inflammation - A case report presenting
      diagnostic difficulties.
AB  - We describe an 86-year-old woman with a history of hypertension who presented
      sudden disturbances of consciousness and left hemiparesis. Brain magnetic
      resonance imaging (MRI) revealed diffused hyperintensive changes on T2-weighted
      images localized subcortically in the white matter of both cerebral hemispheres,
      corresponding to acute vasogenic edema, causing moderate mass effect. Posterior
      reversible encephalopathy syndrome was initially diagnosed. After implementation
      of anti-edema intravenous steroid treatment and hypotensive therapy the symptoms
      began to retire, till the total regression. The successive hospitalizations took
      place two and eight months later due to the occurrence of seizures, motor
      deficits and the development of mild cognitive impairment. Brain MRI revealed
      progression of the white matter changes and diffused subcortical
      microhemorrhages. Each time pulse steroid therapy was implemented and the
      symptoms improved significantly after several days. Chronic oral steroid
      treatment resulted in the stabilization of neurological status. The long-term
      observation of clinical symptoms, remission after immunosuppressive therapy and
      white matter changes with subcortical microhemorrhages in brain MRI leaded to the
      diagnosis of cerebral amyloid angiopathy-related inflammation.

PMID- 29331209
TI  - Ethical and end of life considerations for neonates requiring ECMO support.
AB  - ECMO has proven to be a life-saving intervention for a variety of disease
      entities with a high rate of survival in the neonatal population. However, ECMO
      requires clinical teams to engage in many ethical considerations. Even with
      ongoing improvements in technology and expertise, some patients will not survive
      a course of ECMO. An unsuccessful course of ECMO can be difficult to accept and
      cause a great deal of angst. These questions can result in real conflict both
      within the care team, and between the care team and the family. Herein we explore
      a range of ethical considerations that may be encountered when caring for a
      patient on ECMO, with a particular focus on those courses where it appears likely
      that the patient will not survive. We then consider how a palliative care
      approach may provide a tool set to help engage the team and family in confronting
      the difficult decision to discontinue ECMO.

PMID- 29331210
TI  - To roll the eyes and snap a bite - function, development and evolution of
      craniofacial muscles.
AB  - Craniofacial muscles, muscles that move the eyes, control facial expression and
      allow food uptake and speech, have long been regarded as a variation on the
      general body muscle scheme. However, evidence has accumulated that the function
      of head muscles, their developmental anatomy and the underlying regulatory
      cascades are distinct. This article reviews the key aspects of craniofacial
      muscle and muscle stem cell formation and discusses how this differs from the
      trunk programme of myogenesis; we show novel RNAseq data to support this notion.
      We also trace the origin of head muscle in the chordate ancestors of vertebrates
      and discuss links with smooth-type muscle in the primitive chordate pharynx. We
      look out as to how the special properties of head muscle precursor and stem
      cells, in particular their competence to contribute to the heart, could be
      exploited in regenerative medicine.

PMID- 29331208
TI  - WRIST: A WRist Image Segmentation Toolkit for carpal bone delineation from MRI.
AB  - Segmentation of the carpal bones from 3D imaging modalities, such as magnetic
      resonance imaging (MRI), is commonly performed for in vivo analysis of wrist
      morphology, kinematics, and biomechanics. This crucial task is typically carried
      out manually and is labor intensive, time consuming, subject to high inter- and
      intra-observer variability, and may result in topologically incorrect surfaces.
      We present a method, WRist Image Segmentation Toolkit (WRIST), for 3D semi
      automated, rapid segmentation of the carpal bones of the wrist from MRI. In our
      method, the boundary of the bones were iteratively found using prior known
      anatomical constraints and a shape-detection level set. The parameters of the
      method were optimized using a training dataset of 48 manually segmented carpal
      bones and evaluated on 112 carpal bones which included both healthy participants
      without known wrist conditions and participants with thumb basilar osteoarthritis
      (OA). Manual segmentation by two expert human observers was considered as a
      reference. On the healthy subject dataset we obtained a Dice overlap of 93.0 +/-
      3.8, Jaccard Index of 87.3 +/- 6.2, and a Hausdorff distance of 2.7 +/- 3.4 mm,
      while on the OA dataset we obtained a Dice overlap of 90.7 +/- 8.6, Jaccard Index
      of 83.0 +/- 10.6, and a Hausdorff distance of 4.0 +/- 4.4 mm. The short
      computational time of 20.8 s per bone (or 5.1 s per bone in the parallelized
      version) and the high agreement with the expert observers gives WRIST the
      potential to be utilized in musculoskeletal research.

PMID- 29331211
TI  - Emerging Mechanisms in Alzheimer's Disease and Their Therapeutic Implications.

PMID- 29331212
TI  - Prion Protein as a Toxic Acceptor of Amyloid-beta Oligomers.
AB  - The initial report that cellular prion protein (PrPC) mediates toxicity of
      amyloid-beta species linked to Alzheimer's disease was initially treated with
      scepticism, but growing evidence supports this claim. That there is a high
      affinity interaction is now clear, and its molecular basis is being unraveled,
      while recent studies have identified possible downstream toxic mechanisms.
      Determination of the clinical significance of such interactions between PrPC and
      disease-associated amyloid-beta species will require experimental medicine
      studies in humans. Trials of compounds that inhibit PrP-dependent amyloid-beta
      toxicity are commencing in humans, and although it is clear that only a fraction
      of Alzheimer's disease toxicity could be governed by PrPC, a partial, but still
      therapeutically useful, role in human disease may soon be testable.

PMID- 29331213
TI  - [Methodology for the development of policy brief in public health].
AB  - A policy brief is a document that summarizes research to inform policy. In a
      brief and succinct way, it defines a policy problem, presents a synthesis of
      relevant evidence, identifies possible courses of action and makes
      recommendations or key points. The objective of this note is to describe the
      methodology used to produce a policy brief for communicating public health
      research. This note is based on the model presented by Eugene Bardach in addition
      to the authors' own experiences. We describe six steps: 1) identifying the
      audience; 2) defining the problem; 3) gathering information and evidence; 4)
      consideration of policy alternatives; 5) projecting results and designing
      recommendations; and 6) telling the story. We make a case for the use of policy
      briefs as a part of an overall communications strategy for research that aims to
      bring together research teams and stakeholders.

PMID- 29331214
TI  - The Stockholm-3 Model for Prostate Cancer Detection: Algorithm Update, Biomarker
      Contribution, and Reflex Test Potential.
AB  - BACKGROUND: It has been shown that the Stockholm-3 model (S3M) outperforms
      prostate-specific antigen (PSA) as a screening tool for prostate cancer.
      OBJECTIVE: To update the S3M, to give a detailed account of the value of each
      predictor in the S3M, and to evaluate the S3M as a reflex test for men with PSA
      >=3ng/ml. DESIGN, SETTING, AND PARTICIPANTS: During 2012-2015, the Stockholm-3
      study evaluated the S3M relative to PSA as tests for Gleason score >=7 prostate
      cancers among men aged 50-69 yr. The participants (n=59 159) underwent both
      tests, and biopsy was recommended if at least one was positive. A total of 5073
      men had a biopsy because of elevated PSA (>=3ng/ml). OUTCOME MEASUREMENTS AND
      STATISTICAL ANALYSIS: Logistic regression was used to update the S3M: intact PSA
      was removed, HOXB13 was included, and the model was fitted to data from the
      Stockholm-3 training and validation cohorts. To compare S3M with PSA, we fixed
      the sensitivity for detection of high-grade cancer and evaluated the performance
      as the number of biopsies needed to achieve that sensitivity for each test.
      RESULTS AND LIMITATIONS: The updated S3M slightly improved the area under the
      receiver operating characteristic curve compared to previously published results
      (0.75 vs 0.74). When used as a reflex test for men with PSA >=3ng/ml, S3M reduced
      the number of biopsies needed by 34% compared to the use of PSA alone, with equal
      sensitivity. A limitation is the ethnically homogeneous population. CONCLUSIONS:
      A major problem with PSA screening-too many unnecessary biopsies-can be mitigated
      if S3M is used as a reflex test. PATIENT SUMMARY: To find aggressive prostate
      cancer with the minimum number of negative biopsies and detection of clinically
      insignificant cancers, we evaluated the use of a personalized diagnostic
      prediction model as a second test for men with a positive prostate-specific
      antigen (PSA) test. We found that this two-step approach could reduce prostate
      biopsies by a third compared to using PSA alone.

PMID- 29331215
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.

PMID- 29331216
TI  - Chemoimmunotherapy in Metastatic Urothelial Carcinoma.

PMID- 29331217
TI  - The cost of perioperative complications following pancreaticoduodenectomy: A
      systematic review.
AB  - BACKGROUND/OBJECTIVES: Pancreaticoduodenectomy (PD), also known as a Whipple
      procedure, is commonly performed for a variety of benign and malignant tumours,
      including of the pancreatic head and surrounding structures. PD is associated
      with low mortality but high morbidity and costs. Our objective was to describe
      the financial burden of complications following pancreaticoduodenectomy. METHODS:
      We searched for articles using the MEDLINE, EMBASE, Cochrane and EconLit
      databases from the year 2000. Additional studies were identified by searching
      bibliographies. We included studies reporting on hospital cost or charge of in
      hospital complications during the index PD admission. Studies including other
      surgeries but specifically reporting inpatient complication costs of PD were also
      included. Any type of PD was included. Data was collected using a data extraction
      table and a narrative synthesis was performed. RESULTS: We identified 15 eligible
      articles. All included articles were retrospective studies. Acceptable evidence
      for increased cost due to the presence and grade of complication was found.
      Strong evidence demonstrated the high rate of complications. Weak evidence linked
      complications with specific constituents of hospital cost. Complication grade was
      robustly linked with increased length of stay. Not enough evidence was found to
      demonstrate a link between PD complications and mortality or readmissions.
      LIMITATIONS: Included studies were heterogeneous in setting, methodology, costing
      data, and grading systems. CONCLUSIONS: The presence and grade of PD
      complications increase hospital cost across diverse settings. The costing
      methodology should be transparent and complication grading systems should be
      consistent in future studies. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO
      2017:CRD42017058427.

PMID- 29331218
TI  - Knowing when to stop: Aberrant precision and evidence accumulation in
      schizophrenia.
AB  - Predictive coding and active inference formulations of the dysconnection
      hypothesis suggest that subjects with schizophrenia (SZ) hold unduly precise
      prior beliefs to compensate for a failure of sensory attenuation. This implies
      that SZ subjects should both initiate responses prematurely during evidence
      accumulation tasks and fail to inhibit their responses at long stop-signal
      delays. SZ and healthy control subjects were asked to report the timing of
      billiards-ball collisions and were occasionally required to withhold their
      responses. SZ subjects showed larger temporal estimation errors, which were
      associated with premature responses and decreased response inhibition. To account
      for these effects, we used hierarchical (Bayesian) drift-diffusion models (HDDM)
      and model selection procedures to adjudicate among four hypotheses. HDDM revealed
      that the precision of prior beliefs (i.e., starting point) rather than increased
      sensory precision (i.e., drift rate) drove premature responses and impaired
      response inhibition in patients with SZ. From the perspective of active
      inference, we suggest that premature predictions in SZ are responses that,
      heuristically, are traded off against accuracy to ensure action execution. On the
      basis of previous work, we suggest that the right insular cortex might mediate
      this trade-off.

PMID- 29331219
TI  - Polycyclic aromatic hydrocarbons in soils and lichen from the western Tibetan
      Plateau: Concentration profiles, distribution and its influencing factors.
AB  - The Tibetan Plateau (TP) is a huge area and rarely affected by human activity,
      and is regarded as one of the most remote regions on the earth. Many studies
      about the long-range atmospheric transport (LRAT) of semi-volatile organic
      compounds (SVOCs) were conducted in southern and central TP. However, there are
      very limited studies focused on PAHs in the western TP and the concentrations
      profiles, distribution and its controlling factors in this area remains unclear.
      Thus, to explore this knowledge gap, 37 surface soil samples and 23 lichen
      samples were collected and analyzed for PAHs. The total concentration of 16 US
      EPA's priority PAHs (?16PAHs) in western TP ranges 14.4-59.5ng/g and 38.0-133ng/g
      dry weight (dw) with a mean value of 30.8 and 84.6ng/g dw in soil and lichen,
      respectively, which is lower than the concentrations in most remote areas
      worldwide. In the western TP, low molecular weight PAHs (2-3 rings) are dominant
      (occupied 77.4% and 87.9% on average in soil and lichen, respectively), implying
      a significant contribution of LRAT in this area. The significant linear
      correlations (R2 = 0.372-0.627, p < 0.05) between longitude and soil
      concentration suggest a strong impact of the westerly wind on the distribution of
      PAHs in soil. In addition, the concentration ratio of lichen/soil (L/S) was found
      to linearly increase with the increasing log KOA of individual PAH, suggesting
      lichen has a strong ability in filtering more lipophilic airborne pollutants in
      western TP.

PMID- 29331220
TI  - [Impact of chronic illness on hospital nursing workloads].
AB  - OBJECTIVES: To evaluate the short-term impact of chronic illness in hospital
      units and to establish a method that allows nursing workloads to be adapted
      according to the care needs of patients. METHODS: A descriptive study of the
      evolution of workloads of nursing staff associated with the care needs of
      patients between 1 July 2014 and 30 June 2016, in a county hospital. The care
      needs of the patients were assessed daily using an adaptation of the Montesinos
      scheme. The estimated times of nursing care and auxiliary nursing required by the
      patients, based on their level of dependence for time distribution, were based on
      the standards and recommendations of the Ministry of Health, Social Services and
      Equality. RESULTS: During the study period, there was a change in the patient
      care needs, with no increase in activity, which resulted in an increase in the
      nursing staffing needs of 1,396 theoretical hours per year. This increase implies
      an increase in the workforce of 5 nurses in the second period. CONCLUSIONS: In
      the study period, the needs for direct nursing care increased by 7%, this
      increase is not related to the increase in activity, but to the level of
      dependency of the patients with chronic diseases. This increase occurred in both
      medical and surgical units.

PMID- 29331221
TI  - Mechanisms of changes in functional mitral regurgitation by preload alterations.
AB  - BACKGROUND: This study aimed to investigate the mechanisms of acute changes in
      functional mitral regurgitation (FMR) by preload alterations. METHODS: Twenty-two
      consecutive patients with left ventricular ejection fraction <40% and at least
      mild FMR underwent transthoracic echocardiography. Passive leg lifting and
      sublingual administration of nitroglycerin were performed to alter preload.
      Mitral regurgitant volume (MRV) was assessed using the Doppler method. RESULTS:
      MRV changed in parallel with preload alterations. MRV correlated better with
      tenting height (TH) than with mitral annular area (MAA) at baseline, whereas the
      difference in the correlate coefficients was not statistically significant
      (R=0.69 and R=0.40, respectively; p=0.19). On the other hand, changes in MRV
      between each sequential stage correlated better with those in MAA than with those
      in TH (R=0.68 and R=0.44, respectively; p=0.043). Multiple regression analysis
      revealed that baseline TH was the independent determinant of baseline MRV
      (R=0.69, p=0.0004), whereas changes in MAA with preload alteration were the
      independent determinant of the changes in MRV (R=0.68, p<0.0001). Changes in left
      atrial (LA) volume were the independent determinant of the changes in MAA
      (R=0.30, p=0.0063). CONCLUSIONS: Acute changes in FMR with preload alterations
      resulted from the transverse changes in MAA rather than the longitudinal changes
      in tethering-tenting of mitral geometry, and mitral annular deformation was
      determined by changes in LA volume. Preload reduction might help heart failure
      treatment through the reduction in FMR resulting from the decrease in LA and
      mitral annular size.

PMID- 29331222
TI  - On-tubing fluorescence measurements of the band broadening of contemporary
      injectors in ultra-high performance liquid chromatography.
AB  - We report on a detailed study of the injection contribution to band broadening in
      contemporary UHPLC-instruments, using either flow-through needle or fixed loop
      injection (full loop). Using on-tubing fluorescence measurements at the outlet of
      the injector valve, very localized and undisturbed measurements were obtained.
      Varying both the flow rate and the injected volume allowed to split the injection
      variance (sigmaV2,inj) in a volumetric component (related to the amount injected)
      and a hydrodynamic component (related to the flow rate). For the flow-through
      needle injector and for the small injection volumes (<2 MUL) typically used in
      UHPLC, it was found that the volumetric contribution (i.e. the part of
      sigmaV2,inj, that increases with increasing injection volume) is given by a value
      of sigmaV2,inj,vol = 0.8 to 1.Vinj2 rather than by the value of 0.125 to
      0.2.Vinj2 that is normally assumed in literature. For the hydrodynamic
      contribution to sigmaV2,inj, (i..e, the part which remains present even for very
      small injection volumes), a clear increase in dispersion with flow rate is found,
      reaching a plateau around 0.8ml/min of 0.6 MUL2 or 1.2 MUL2 for the 75 MUm and
      120 MUm needle seat capillaries respectively. The difference between both shows
      the clear advantage of using a low dispersion 75 MUm injection needle seat
      capillary. For a loop-type injector operated in a full-loop mode, the increase in
      peak variance with the injection volume is much less pronounced, leading to a
      total injector variance given by sigmaV2,inj = 0.34 MUL2 + 0.12.Vinj2 over the
      entire range of investigated injection volumes of 1.1 MUL up to 4.5 MUL when
      using 120 MUm or narrower ID loops. This expression was nearly completely
      independent of the flow rate. For larger ID sample loops, a clear increase of
      peak variance with flow rate at fixed injection volume was observed (sigmaV2,inj
      increases with 20% for a 170 MUm ID loop and with 70% for a 220 MUm ID loop from
      0.3 to 1 ml/min).

PMID- 29331223
TI  - Structure-based design and application of a nucleotide coenzyme mimetic ligand:
      Application to the affinity purification of nucleotide dependent enzymes.
AB  - In the present study, a structure-based approach was exploited for the in silico
      design of a nucleotide coenzyme mimetic ligand. The enzyme formate dehydrogenase
      (FDH) was employed as a model in our study. The biomimetic ligand was designed
      and synthesized based on a tryptamine/3-aminopropylphosphonic acid bi-substituted
      1,3,5-triazine (Trz) scaffold (Tra-Trz-3APP), which potentially mimics the
      interactions of NAD+-FDH complex. Molecular docking studies of the biomimetic
      ligand predicted that it can occupy the same binding site as the natural
      coenzyme. Molecular modeling and dynamics simulations revealed that the ligand
      binds in an energetically more stable pose in the FDH binding site, as it adopts
      a more twisty conformation, compared to the natural coenzyme. Study of the
      FDH/Tra-Trz-3APP-Sepharose interaction, through adsorption equilibrium studies
      and site-directed mutagenesis of selected FDH coenzyme binding residues, provided
      additional experimental evidences of the specificity of the interaction. The Tra
      Trz-3APP-Sepharose biomimetic adsorbent was further evaluated towards a range of
      different dehydrogenases and was exploited for the development of a single-step
      purification protocol for FDH. The protocol afforded enzyme with high yield and
      purity, suitable for analytical and industrial purposes.

PMID- 29331224
TI  - Centrifugal partition chromatography enables selective enrichment of trimeric and
      tetrameric proanthocyanidins for biomaterial development.
AB  - Proanthocyanidins (PACs) find wide applications for human use including food,
      cosmetics, dietary supplements, and pharmaceuticals. The chemical complexity
      associated with PACs has triggered the development of various chromatographic
      techniques, with countercurrent separation (CCS) gaining in popularity. This
      study applied the recently developed DESIGNER (Depletion and Enrichment of Select
      Ingredients Generating Normalized Extract Resources) approach for the selective
      enrichment of trimeric and tetrameric PACs using centrifugal partition
      chromatography (CPC). This CPC method aims at developing PAC based biomaterials,
      particularly for their application in restoring and repairing dental hard tissue.
      A general separation scheme beginning with the depletion of polymeric PACs,
      followed by the removal of monomeric flavan-3-ols and a final enrichment step
      produced PAC trimer and tetramer enriched fractions. A successful application of
      this separation scheme is demonstrated for four polyphenol rich plant sources:
      grape seeds, pine bark, cinnamon bark, and cocoa seeds. Minor modifications to
      the generic DESIGNER CCS method were sufficient to accommodate the varying
      chemical complexities of the individual source materials. The step-wise
      enrichment of PAC trimers and tetramers was monitored using normal phase TLC and
      Diol-HPLC-UV analyses. CPC proved to be a reliable tool for the selective
      enrichment of medium size oligomeric PACs (OPACs). This method plays a key role
      in the development of dental biomaterials considering its reliability and
      reproducibility, as well as its scale-up capabilities for possible larger-scale
      manufacturing.

PMID- 29331225
TI  - Influence of pressure on the retention of resorcinarene-based cavitands.
AB  - The thermodynamics of the retention mechanism of resorcinarene-based cavitands in
      RPLC as well as the nature of the binding sites have been studied recently. In
      the present study, the influence of pressure on the retention of the cyclic
      tetramers on alkylsilyl and polar-embedded C8 and C18 stationary phases is
      investigated using aqueous methanol mobile phase. The pressure effect for cavity
      shaped molecules has been scarcely studied so far. We observed that the retention
      factors of the analytes increased with the increase of the average column
      pressure (1-400 bar) when using restricting capillary tubes. The calculated molar
      volume changes were negative, between -DeltaVm = 5-19 mL/mol on all types of
      stationary phases. Comparing the different stationary phases, we found that the
      molar volume changes for both the apolar and more polar analytes were twice
      larger on the Hypersil BDS (base deactivated silica) than on the XTerra columns
      and they were independent of the length of the alkyl chains of the stationary
      phases.

PMID- 29331226
TI  - A low complexity minimum variance beamformer for ultrasound imaging using
      dominant mode rejection.
AB  - In recent years, high resolution adaptive minimum variance-based beamformers have
      been successfully applied to medical ultrasound imaging to improve its resolution
      and contrast, simultaneously. However, these improvements come at the cost of
      much more computational complexity in comparison to the non-adaptive delay-and
      sum beamformer. The computational overhead mainly results from the L*L covariance
      matrix inversion needed for computation of the adaptive weights, the complexity
      of which is cubic with the subarray size, O(L3). In medical ultrasound imaging
      with focusing on the imaging point, we have a limited number of dominant modes
      and there is no need for the full matrix inversion. Based on this idea, we have
      investigated the application of the dominant mode rejection (DMR) adaptive
      beamformer for medical ultrasound imaging, which uses only some largest dominant
      modes to approximate the covariance matrix in dominant subspace. We show, using
      simulated and experimental data, that this subspace dimension can be selected as
      low as two resulting in significant computational complexity reduction while
      still achieving performance comparable to that of the minimum variance
      beamformer.

PMID- 29331229
TI  - Hominin raw material procurement in the Oldowan-Acheulean transition at Olduvai
      Gorge.
AB  - The lithic assemblages at the Oldowan-Acheulean transition in Bed II of Olduvai
      Gorge, Tanzania, represent a wide variety of raw materials reflecting both the
      diversity of volcanic, metamorphic, and sedimentary source materials available in
      the Olduvai basin and surroundings and the preferences of the tool-makers. A
      geochemical and petrographic systematic analysis of lava-derived archaeological
      stone tools, combined with textural and mineralogical characterization of
      quartzite, chert, and other metamorphic and sedimentary raw materials from two
      Middle and Upper Bed II sites, has enabled us to produce a comprehensive dataset
      and characterization of the rocks employed by Olduvai hominins, which is used
      here to establish a referential framework for future studies on Early Stone Age
      raw material provenancing. The use of rounded blanks for most lava-derived
      artifacts demonstrates that hominins were accessing lava in local stream
      channels. Most quartzite artifacts appear to derive from angular blocks, likely
      acquired at the source (predominantly Naibor Soit hill), though some do appear to
      be manufactured from stream-transported quartzite blanks. Raw material
      composition of the EF-HR assemblage indicates that Acheulean hominins selected
      high-quality lavas for the production of Large Cutting Tools. On the other hand,
      the HWK EE lithic assemblage suggests that raw material selectivity was not
      entirely based on rock texture, and other factors, such as blank shape and
      availability of natural angles suitable for flaking, played a major role in
      Oldowan reduction sequences.

PMID- 29331230
TI  - Lower limb articular scaling and body mass estimation in Pliocene and Pleistocene
      hominins.
AB  - Previous attempts to estimate body mass in pre-Holocene hominins have relied on
      prediction equations derived from relatively limited extant samples. Here we
      derive new equations to predict body mass from femoral head breadth and proximal
      tibial plateau breadth based on a large and diverse sample of modern humans
      (avoiding the problems associated with using diaphyseal dimensions and/or
      cadaveric reference samples). In addition, an adjustment for the relatively small
      femoral heads of non-Homo taxa is developed based on observed differences in hip
      to knee joint scaling. Body mass is then estimated for 214 terminal Miocene
      through Pleistocene hominin specimens. Mean body masses for non-Homo taxa range
      between 39 and 49 kg (39-45 kg if sex-specific means are averaged), with no
      consistent temporal trend (6-1.85 Ma). Mean body mass increases in early Homo
      (2.04-1.77 Ma) to 55-59 kg, and then again dramatically in Homo erectus and later
      archaic middle Pleistocene Homo, to about 70 kg. The same average body mass is
      maintained in late Pleistocene archaic Homo and early anatomically modern humans
      through the early/middle Upper Paleolithic (0.024 Ma), only declining in the late
      Upper Paleolithic, with regional variation. Sexual dimorphism in body mass is
      greatest in Australopithecus afarensis (log[male/female] = 1.54), declines in
      Australopithecus africanus and Paranthropus robustus (log ratio 1.36), and then
      again in early Homo and middle and late Pleistocene archaic Homo (log ratio 1.20
      1.27), although it remains somewhat elevated above that of living and middle/late
      Pleistocene anatomically modern humans (log ratio about 1.15).

PMID- 29331231
TI  - Successful catheter ablation of atrioventricular reentrant tachycardia with left
      lateral bypass tract in a patient with unroofed coronary sinus atrial septal
      defect.

PMID- 29331227
TI  - The impact of technology on the changing practice of lung SBRT.
AB  - Stereotactic body radiotherapy (SBRT) for lung tumours has been gaining wide
      acceptance in lung cancer. Here, we review the technological evolution of SBRT
      delivery in lung cancer, from the first treatments using the stereotactic body
      frame in the 1990's to modern developments in image guidance and motion
      management. Finally, we discuss the impact of current technological approaches on
      the requirements for quality assurance as well as future technological
      developments.

PMID- 29331232
TI  - Incorporating behavioral and sensory context into spectro-temporal models of
      auditory encoding.
AB  - For several decades, auditory neuroscientists have used spectro-temporal encoding
      models to understand how neurons in the auditory system represent sound. Derived
      from early applications of systems identification tools to the auditory
      periphery, the spectro-temporal receptive field (STRF) and more sophisticated
      variants have emerged as an efficient means of characterizing representation
      throughout the auditory system. Most of these encoding models describe neurons as
      static sensory filters. However, auditory neural coding is not static. Sensory
      context, reflecting the acoustic environment, and behavioral context, reflecting
      the internal state of the listener, can both influence sound-evoked activity,
      particularly in central auditory areas. This review explores recent efforts to
      integrate context into spectro-temporal encoding models. It begins with a brief
      tutorial on the basics of estimating and interpreting STRFs. Then it describes
      three recent studies that have characterized contextual effects on STRFs,
      emerging over a range of timescales, from many minutes to tens of milliseconds.
      An important theme of this work is not simply that context influences auditory
      coding, but also that contextual effects span a large continuum of internal
      states. The added complexity of these context-dependent models introduces new
      experimental and theoretical challenges that must be addressed in order to be
      used effectively. Several new methodological advances promise to address these
      limitations and allow the development of more comprehensive context-dependent
      models in the future.

PMID- 29331233
TI  - A biophysical modelling platform of the cochlear nucleus and other auditory
      circuits: From channels to networks.
AB  - Models of the auditory brainstem have been an invaluable tool for testing
      hypotheses about auditory information processing and for highlighting the most
      important gaps in the experimental literature. Due to the complexity of the
      auditory brainstem, and indeed most brain circuits, the dynamic behavior of the
      system may be difficult to predict without a detailed, biologically realistic
      computational model. Despite the sensitivity of models to their exact
      construction and parameters, most prior models of the cochlear nucleus have
      incorporated only a small subset of the known biological properties. This
      confounds the interpretation of modelling results and also limits the potential
      future uses of these models, which require a large effort to develop. To address
      these issues, we have developed a general purpose, biophysically detailed model
      of the cochlear nucleus for use both in testing hypotheses about cochlear nucleus
      function and also as an input to models of downstream auditory nuclei. The model
      implements conductance-based Hodgkin-Huxley representations of cells using a
      Python-based interface to the NEURON simulator. Our model incorporates most of
      the quantitatively characterized intrinsic cell properties, synaptic properties,
      and connectivity available in the literature, and also aims to reproduce the
      known response properties of the canonical cochlear nucleus cell types. Although
      we currently lack the empirical data to completely constrain this model, our
      intent is for the model to continue to incorporate new experimental results as
      they become available.

PMID- 29331235
TI  - Antimullerian hormone as a predictor of live birth following assisted
      reproduction: an analysis of 85,062 fresh and thawed cycles from the Society for
      Assisted Reproductive Technology Clinic Outcome Reporting System database for
      2012-2013.
AB  - OBJECTIVE: To determine if serum antimullerian hormone (AMH) is associated with
      and/or predictive of live birth assisted reproductive technology (ART) outcomes.
      DESIGN: Retrospective analysis of Society for Assisted Reproductive Technology
      Clinic Outcome Reporting System database from 2012 to 2013. SETTING: Not
      applicable. PATIENT(S): A total of 69,336 (81.8%) fresh and 15,458 (18.2%) frozen
      embryo transfer (FET) cycles with AMH values. INTERVENTION(S): None. MAIN OUTCOME
      MEASURE(S): Live birth. RESULT(S): A total of 85,062 out of 259,499 (32.7%) fresh
      and frozen-thawed autologous non-preimplantation genetic diagnosis cycles had AMH
      reported for cycles over this 2-year period. Of those, 70,565 cycles which had
      embryo transfers were included in the analysis. Serum AMH was significantly
      associated with live birth outcome per transfer in both fresh and FET cycles.
      Multiple logistic regression demonstrated that AMH is an independent predictor of
      live birth in fresh transfer cycles and FET cycles when controlling for age, body
      mass index, race, day of transfer, and number of embryos transferred. Receiver
      operating characteristic (ROC) curves demonstrated that the areas under the curve
      (AUC) for AMH as predictors of live birth in fresh cycles and thawed cycles were
      0.631 and 0.540, respectively, suggesting that AMH alone is a weak independent
      predictor of live birth after ART. Similar ROC curves were obtained also when
      elective single-embryo transfer (eSET) cycles were analyzed separately in either
      fresh (AUC 0.655) or FET (AUC 0.533) cycles, although AMH was not found to be an
      independent predictor in eSET cycles. CONCLUSION(S): AMH is a poor independent
      predictor of live birth outcome in either fresh or frozen embryo transfer for
      both eSET and non-SET transfers.

PMID- 29331234
TI  - Metabolic syndrome, hypertension, and hyperlipidemia in mothers, fathers,
      sisters, and brothers of women with polycystic ovary syndrome: a systematic
      review and meta-analysis.
AB  - OBJECTIVE: To provide an evidence-based assessment of metabolic syndrome,
      hypertension, and hyperlipidemia in first-degree relatives of women with
      polycystic ovary syndrome (PCOS). DESIGN: Systematic review and meta-analysis.
      SETTING: Not applicable. PATIENT(S): Mothers, fathers, sisters, and brothers of
      women with and without PCOS. INTERVENTION(S): An electronic-based search with the
      use of PubMed from 1960 to June 2015 and cross-checked references of relevant
      articles. MAIN OUTCOME MEASURE(S): Metabolic syndrome, hypertension and
      dyslipidemia, and surrogate markers, including systolic blood pressure (BP),
      diastolic BP, total cholesterol, low-density lipoprotein cholesterol, high
      density lipoprotein cholesterol, and triglycerides. RESULT(S): Fourteen of 3,346
      studies were included in the meta-analysis. Prevalence of the following was
      significantly increased in relatives of women with PCOS: metabolic syndrome (risk
      ratio [RR] 1.78 [95% confidence interval 1.37, 2.30] in mothers, 1.43 [1.12,
      1.81] in fathers, and 1.50 [1.12, 2.00] in sisters), hypertension (RR 1.93 [1.58,
      2.35] in fathers, 2.92 [1.92, 4.45] in sisters), and dyslipidemia (RR 3.86 [2.54,
      5.85] in brothers and 1.29 [1.11, 1.50] in fathers). Moreover, systolic BP
      (mothers, sisters, and brothers), total cholesterol (mothers and sisters), low
      density lipoprotein cholesterol (sisters), and triglycerides (mothers and
      sisters) were significantly higher in first-degree relatives of PCOS probands
      than in controls. CONCLUSION(S): Our results show evidence of clustering for
      metabolic syndrome, hypertension, and dyslipidemia in mothers, fathers, sisters,
      and brothers of women with PCOS. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO
      2016 CRD42016048557.

PMID- 29331236
TI  - Pregnancy-related complications and perinatal outcomes resulting from transfer of
      cryopreserved versus fresh embryos in vitro fertilization: a meta-analysis.
AB  - OBJECTIVE: To provide an updated comparison of pregnancy-related complications
      and adverse perinatal outcomes of pregnancies conceived after frozen embryo
      transfer (FET) versus fresh embryo transfer (fresh ET). DESIGN: Meta-analysis.
      SETTING: University. PATIENT(S): Pregnancies resulting from FET versus fresh ET.
      INTERVENTIONS(S): Pubmed, Embase, Cochrane Library, Google Scholar, and Chinese
      databases, including the China National Knowledge Infrastructure Database,
      Wanfang, and Chinese Scientific Journals Full-Text Database were searched by two
      independent reviewers from January 1980 to September 2017. The results were
      expressed as risk ratios with 95% confidence intervals. MAIN OUTCOME MEASURE(S):
      Pregnancy-related complications and perinatal outcomes. RESULT(S): Our search
      retrieved 1,397 articles, of which 31 studies were included. Pregnancies
      resulting from FET were associated with lower relative risks of placenta previa,
      placental abruption, low birth weight, very low birth weight, very preterm birth,
      small for gestational age, and perinatal mortality compared with fresh ET.
      Pregnancies occurring from FET were associated with increased risks of pregnancy
      induced hypertension, postpartum hemorrhage, and large for gestational age
      compared with fresh ET. The risks of gestational diabetes mellitus, preterm
      premature rupture of the membranes, and preterm birth (PTB) showed no differences
      between the two groups. CONCLUSION(S): Our analysis demonstrated that FET results
      in lower risks of placenta previa, placental abruption, low birth weight, very
      low birth weight, very preterm birth, small for gestational age, and perinatal
      mortality than fresh ET, some differences that are attributed to the increased
      risks of pregnancy-induced hypertension, large for gestational age, and
      postpartum hemorrhage. Although cryotechnology keeps improving, for comprehensive
      consideration, individual approaches remain appropriate to balance the options of
      FET or fresh ET at present.

PMID- 29331237
TI  - Time-lapse algorithms and morphological selection of day-5 embryos for transfer:
      a preclinical validation study.
AB  - OBJECTIVE: To determine the agreement between published time-lapse algorithms in
      selecting the best day-5 embryo for transfer, as well as the agreement between
      these algorithms and embryologists. DESIGN: Prospective study. SETTING: Private
      in vitro fertilization center. PATIENT(S): Four hundred and twenty-eight embryos
      from 100 cycles cultured in the EmbryoScope. INTERVENTION(S): None. MAIN OUTCOME
      MEASURE(S): Interalgorithm agreement as assessed by the Fleiss kappa coefficient.
      RESULT(S): Of seven published algorithms analyzed in this study, only one of the
      18 possible pairs showed very good agreement (kappa = 0.867); one pair showed
      good agreement (kappa = 0.725), four pairs showed fair agreement (kappa = 0.226
      0.334), and the remaining 12 pairs showed poor agreement (kappa = 0.008-0.149).
      Even in the best-case scenario, the majority of algorithms showed poor to
      moderate kappa scores (kappa = 0.337-0.722) for the assessment of agreement
      between the embryo(s) selected as "best" by the algorithms and the embryo that
      was chosen by the majority (>5) of embryologists, as well as with the embryo that
      was actually selected in the laboratory on the day of transfer (kappa = 0.315
      0.802). CONCLUSION(S): The results of this study raise concerns as to whether the
      tested algorithms are applicable in different clinical settings, emphasizing the
      need for proper external validation before clinical use.

PMID- 29331238
TI  - In vitro fertilization twins: acceptable when desired, or iatrogenic complication
      preventable through elective single embryo transfer?

PMID- 29331239
TI  - Sperm donor anonymity: a concept rendered obsolete by modern technology.

PMID- 29331240
TI  - A new predictive parameter for embryo transfer success: a path forward is needed
      to implement it in technique training.

PMID- 29331241
TI  - Evaluation of MALDI-TOF mass spectrometry for the identification of bacteria
      growing as biofilms.
AB  - We evaluated MALDI-TOF mass spectrometry to identify bacteria from biofilms. We
      compared three sample preparation procedures on biofilms grown in vitro. The
      extended direct transfer method was able to identify 13 isolates out of 18 (72%)
      at the species level and 15 out of 18 (83%) at the genus level.

PMID- 29331242
TI  - Species-specific response to sulfide intrusion in native and exotic Mediterranean
      seagrasses under stress.
AB  - We explored the sulfur dynamics and the relationships between sediment sulfur and
      nutrient pools, seagrass structural and physiological variables and sulfide
      intrusion in native (Posidonia oceanica, Cymodocea nodosa) and exotic (Halophila
      stipulacea) Mediterranean seagrasses at six sites affected by cumulative
      anthropogenic pressures to understand the factors controlling sulfide intrusion
      in seagrass. Sensitive indicators of seagrass stress (leaf TN, delta15N, TS,
      Fsulfide) were increased at several sites, implying that seagrasses are under
      pressure. Sulfide intrusion was not related to sediment TOC but it was negatively
      related to shoot size and below-ground biomass. Sulfide intrusion in seagrass
      tissue was high in P. oceanica (12-17%) and considerably higher in C. nodosa (27
      35%). Intrusion was particularly high in H. stipulacea (30-50%), suggesting that
      its possible biogeographical expansion due to warming of the Mediterranean may
      result in accumulation of sulfides in the sediments and hypoxia/anoxia with
      further implications in ecosystem function.

PMID- 29331243
TI  - Tolerance and potential for adaptation of a Baltic Sea rockweed under predicted
      climate change conditions.
AB  - Climate change is threating species' persistence worldwide. To predict species
      responses to climate change we need information not just on their environmental
      tolerance but also on its adaptive potential. We tested how the foundation
      species of rocky littoral habitats, Fucus vesiculosus, responds to combined
      hyposalinity and warming projected to the Baltic Sea by 2070-2099. We quantified
      responses of replicated populations originating from the entrance, central, and
      marginal Baltic regions. Using replicated individuals, we tested for the presence
      of within-population tolerance variation. Future conditions hampered growth and
      survival of the central and marginal populations whereas the entrance populations
      fared well. Further, both the among- and within-population variation in responses
      to climate change indicated existence of genetic variation in tolerance. Such
      standing genetic variation provides the raw material necessary for adaptation to
      a changing environment, which may eventually ensure the persistence of the
      species in the inner Baltic Sea.

PMID- 29331244
TI  - Perception of faunal circadian rhythms depends on sampling technique.
AB  - Ecologists aim at disentangling how species vary in abundance through spatial and
      temporal scales, using a range of sampling techniques. Here, we investigated the
      circadian rhythm of seagrass-associated decapod crustaceans through three
      sampling techniques. Specifically, we compared the abundance, biomass and
      structure of seagrass-associated decapod assemblages between the day and night
      using a hand net, an airlift pump and baited traps. At night, the hand-net
      consistently collected a larger total abundance and biomass of decapods, what
      resulted in significant diel differences, which were detected for the total
      biomass, but not for the total abundance, when decapods were sampled through an
      airlift pump. Traps, however, collected a larger total abundance, but not total
      biomass, of decapods during the night. In summary, our perception of faunal diel
      rhythms is notably influence by the way organisms are sampled.

PMID- 29331245
TI  - Outsmart HPV: Acceptability and short-term effects of a web-based HPV vaccination
      intervention for young adult gay and bisexual men.
AB  - BACKGROUND: Effective interventions to promote human papillomavirus (HPV)
      vaccination are needed, particularly among populations at increased risk of HPV
      related disease. We developed and pilot tested a web-based intervention, Outsmart
      HPV, to promote HPV vaccination among young gay and bisexual men (YGBM). METHODS:
      In 2016, we recruited a national sample (n = 150) of YGBM ages 18-25 in the
      United States who had not received any doses of HPV vaccine. Participants were
      randomized to receive either standard HPV vaccination information (control) or
      population-targeted, individually-tailored content (Outsmart HPV intervention).
      We assessed between group differences in HPV vaccination attitudes and beliefs
      immediately following the intervention using multiple linear regression. RESULTS:
      There were no differences in HPV vaccination attitudes, beliefs and intentions
      between groups at baseline. Compared to participants in the control group,
      intervention participants reported: greater perception that men who have sex with
      men are at higher risk for anal cancer relative to other men (b = 0.34); greater
      HPV vaccination self-efficacy (b = 0.15); and fewer perceived harms of HPV
      vaccine (b = -0.34) on posttest surveys (all p < .05). Overall, intervention
      participants reported high levels of acceptability and satisfaction with the
      Outsmart HPV intervention (all > 4.4 on a 5-point scale). CONCLUSIONS: Findings
      from this study provide preliminary support for a brief, tailored web-based
      intervention in improving HPV vaccination attitudes and beliefs among YGBM. An
      important next step is to determine the effects of Outsmart HPV on HPV vaccine
      uptake. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier NCT02835755.

PMID- 29331246
TI  - Estimation of expected dengue seroprevalence from passive epidemiological
      surveillance systems in selected areas of Argentina: A proxy to evaluate the
      applicability of dengue vaccination.
AB  - BACKGROUND: Current recommendations about dengue vaccination by the World Health
      Organization depend on seroprevalence levels and serological status in
      populations and individuals. However, seroprevalence estimation may be difficult
      due to a diversity of factors. Thus, estimation through models using data from
      epidemiological surveillance systems could be an alternative procedure to achieve
      this goal. OBJECTIVE: To estimate the expected dengue seroprevalence in children
      of selected areas in Argentina, using a simple model based on data from passive
      epidemiological surveillance systems. METHODS: A Markov model using a simulated
      cohort of individuals from age 0 to 9 years was developed. Parameters regarding
      the reported annual incidence of dengue, proportion of inapparent cases, and
      expansion factors for outpatient and hospitalized cases were considered as
      transition probabilities. The proportion of immune population at 9 years of age
      was taken as a proxy of the expected seroprevalence, considering this age as
      targeted for vaccination. The model was used to evaluate the expected
      seroprevalence in Misiones and Salta provinces and in Buenos Aires city, three
      settings showing different climatic favorability for dengue. RESULTS: The
      estimates of the seroprevalence for the group of 9-year-old children for Misiones
      was 79% (95%CI:46-100%), and for Salta 22% (95%CI:14-30%), both located in
      northeastern and northwestern Argentina, respectively. Buenos Aires city, from
      central Argentina, showed a likely seroprevalence of 7% (95%CI: 3-11%). According
      to the deterministic sensitivity analyses, the parameter showing the highest
      influence on these results was the probability of inapparent cases. CONCLUSIONS:
      This model allowed the estimation of dengue seroprevalence in settings where this
      information is not available. Particularly for Misiones, the expected
      seroprevalence was higher than 70% in a wide range of scenarios, thus in this
      province a vaccination strategy directed to seropositive children of >9 years
      should be analyzed, including further considerations as safety, cost
      effectiveness, and budget impact.

PMID- 29331247
TI  - A biopsy of Breast Cancer mobile applications: state of the practice review.
AB  - BACKGROUND: Breast cancer is the most common cancer in women. The use of mobile
      software applications for health and wellbeing promotion has grown exponentially
      in recent years. We systematically reviewed the breast cancer apps available in
      today's leading smartphone application stores and characterized them based on
      their features, evidence base and target audiences. METHODS: A cross-sectional
      study was performed to characterize breast cancer apps from the two major
      smartphone app stores (iOS and Android). Apps that matched the keywords "breast
      cancer" were identified and data was extracted using a structured form. Reviewers
      independently evaluated the eligibility and independently classified the apps.
      RESULTS: A total of 1473 apps were a match. After removing duplicates and
      applying the selection criteria only 599 apps remained. Inter-rater reliability
      was determined using Fleiss-Cohen's Kappa. The majority of apps were free 471
      (78.63%). The most common type of application was Disease and Treatment
      information apps (29.22%), Disease Management (19.03%) and Awareness Raising apps
      (15.03%). Close to 1 out of 10 apps dealt with alternative or homeopathic
      medicine. The majority of the apps were intended for patients (75.79%). Only one
      quarter of all apps (24.54%) had a disclaimer about usage and less than one fifth
      (19.70%) mentioned references or source material. Gamification specialists
      determined that 19.36% contained gamification elements. CONCLUSIONS: This study
      analyzed a large number of breast cancer-focused apps available to consumers.
      There has been a steady increase of breast cancer apps over the years. The breast
      cancer app ecosystem largely consists of start-ups and entrepreneurs. Evidence
      base seems to be lacking in these apps and it would seem essential that expert
      medical personnel be involved in the creation of medical apps.

PMID- 29331249
TI  - Digital health: A science at crossroads.

PMID- 29331248
TI  - Usability evaluation of a commercial inpatient portal.
AB  - OBJECTIVES: Patient portals designed for inpatients have potential to increase
      patient engagement. However, little is known about how patients use inpatient
      portals. To address this gap, we aimed to understand how users 1) interact with,
      2) learn to use, and 3) communicate with their providers through an inpatient
      portal. MATERIALS AND METHODS: We conducted a usability evaluation using think
      aloud protocol to study user interactions with a commercially available inpatient
      portal - MyChart Bedside (MCB). Study participants (n=19) were given a tablet
      that had MCB installed. They explored MCB and completed eight assigned tasks.
      Each session's recordings were coded and analyzed. We analyzed task completion,
      errors, and user feedback. We categorized errors into operational errors, system
      errors, and tablet-related errors, and indicated their violations of Nielsen's
      ten heuristic principles. RESULTS: Participants frequently made operational
      errors with most in navigation and assuming non-existent functionalities. We also
      noted that participants' learning styles varied, with age as a potential factor
      that influenced how they learned MCB. Also, participants preferred to
      individually message providers and wanted feedback on status. CONCLUSION: The
      design of inpatient portals can greatly impact how patients navigate and
      comprehend information in inpatient portals; poor design can result in a
      frustrating user experience. For inpatient portals to be effective in promoting
      patient engagement, it remains critical for technology developers and hospital
      administrators to understand how users interact with this technology and the
      resources that may be necessary to support its use.

PMID- 29331250
TI  - Inferred joint multigram models for medical term normalization according to ICD.
AB  - BACKGROUND: Electronic Health Records (EHRs) are written using spontaneous
      natural language. Often, terms do not match standard terminology like the one
      available through the International Classification of Diseases (ICD). OBJECTIVE:
      Information retrieval and exchange can be improved using standard terminology.
      Our aim is to render diagnostic terms written in spontaneous language in EHRs
      into the standard framework provided by the ICD. METHODS: We tackle diagnostic
      term normalization employing Weighted Finite-State Transducers (WFSTs). These
      machines learn how to translate sequences, in the case of our concern,
      spontaneous representations into standard representations given a set of samples.
      They are highly flexible and easily adaptable to terminological singularities of
      each different hospital and practitioner. Besides, we implemented a similarity
      metric to enhance spontaneous-standard term matching. RESULTS: From the 2850
      spontaneous DTs randomly selected we found that only 7.71% were written in their
      standard form matching the ICD. This WFST-based system enabled matching
      spontaneous ICDs with a Mean Reciprocal Rank of 0.68, which means that, on
      average, the right ICD code is found between the first and second position among
      the normalized set of candidates. This guarantees efficient document exchange
      and, furthermore, information retrieval. CONCLUSION: Medical term normalization
      was achieved with high performance. We found that direct matching of spontaneous
      terms using standard lexicons leads to unsatisfactory results while normalized
      hypothesis generation by means of WFST helped to overcome the gap between
      spontaneous and standard language.

PMID- 29331251
TI  - Bridging clinical researcher perceptions and health IT realities: A case study of
      stakeholder creep.
AB  - PURPOSE: We present a case report detailing a challenge in health information
      technology (HIT) project implementations we term "stakeholder creep": not
      thoroughly identifying which stakeholders need to be involved and why before
      starting a project, consequently not understanding the true effort, skill sets,
      social capital, and time required to complete the project. METHODS: A root cause
      analysis was performed post-implementation to understand what led to stakeholder
      creep. HIT project stakeholders were given a questionnaire to comment on these
      misconceptions and a proposed implementation tool to help mitigate stakeholder
      creep. FINDINGS: Stakeholder creep contributed to an unexpected increase in time
      (3-month delayed go-live) and effort (68% over expected HIT work hours). Four
      main clinician/researcher misconceptions were identified that contributed to the
      development of stakeholder creep: 1) that EHR IT is a single group; 2) that all
      EHR IT members know the entire EHR functionality; 3) that changes to an EHR need
      the input of just a single EHR IT member; and 4) that the technological
      complexity of a project mirrors the clinical complexity. HIT project stakeholders
      similarly perceived clinicians/researchers to hold these misconceptions. The
      proposed stakeholder planning tool was perceived to be feasible and helpful.
      CONCLUSIONS: Stakeholder creep can negatively affect HIT project implementations.
      Projects may be susceptible to stakeholder creep when clinicians/researchers hold
      misconceptions related to HIT organization and processes. Implementation tools,
      such as the proposed stakeholder checklist, could be helpful in preempting and
      mitigating the effect of stakeholder creep.

PMID- 29331252
TI  - Investigating the need for clinicians to use tablet computers with a newly
      envisioned electronic health record.
AB  - OBJECTIVE: The Veterans Health Administration (VHA) has deployed a large number
      of tablet computers in the last several years. However, little is known about how
      clinicians may use these devices with a newly planned Web-based electronic health
      record (EHR), as well as other clinical tools. The objective of this study was to
      understand the types of use that can be expected of tablet computers versus
      desktops. METHODS: Semi-structured interviews were conducted with 24 clinicians
      at a Veterans Health Administration (VHA) Medical Center. RESULTS: An inductive
      qualitative analysis resulted in findings organized around recurrent themes of:
      (1) Barriers, (2) Facilitators, (3) Current Use, (4) Anticipated Use, (5) Patient
      Interaction, and (6) Connection. CONCLUSIONS: Our study generated several
      recommendations for the use of tablet computers with new health information
      technology tools being developed. Continuous connectivity for the mobile device
      is essential to avoid interruptions and clinician frustration. Also, making a
      physical keyboard available as an option for the tablet was a clear desire from
      the clinicians. Larger tablets (e.g., regular size iPad as compared to an iPad
      mini) were preferred. Being able to use secure messaging tools with the tablet
      computer was another consistent finding. Finally, more simplicity is needed for
      accessing patient data on mobile devices, while balancing the important need for
      adequate security.

PMID- 29331253
TI  - Evaluation of three machine learning models for self-referral decision support on
      low back pain in primary care.
AB  - BACKGROUND: Most people experience low back pain (LBP) at least once in their
      life and for some patients this evolves into a chronic condition. One way to
      prevent acute LBP from transiting into chronic LBP, is to ensure that patients
      receive the right interventions at the right moment. We started research in the
      design of a clinical decision support system (CDSS) to support patients with LBP
      in their self-referral to primary care. For this, we explored the possibilities
      of using supervised machine learning. We compared the performances of the three
      classification models - i.e. 1. decision tree, 2. random forest, and 3. boosted
      tree - to get insight in which model performs best and whether it is already
      acceptable to use this model in real practice. METHODS: The three models were
      generated by means of supervised machine learning with 70% of a training dataset
      (1288 cases with 65% GP, 33% physio, 2% self-care cases). The cases in the
      training dataset were fictive cases on low back pain collected during a vignette
      study with primary healthcare professionals. We also wanted to know the
      performance of the models on real-life low back pain cases that were not used to
      train the models. Therefore we also collected real-life cases on low back pain as
      test dataset. These cases were collected with the help of patients and healthcare
      professionals in primary care. For each model, the performance was measured
      during model validation - with 30% of the training dataset -as well as during
      model testing - with the test dataset containing real-life cases. The total
      observed accuracy as well as the kappa, and the sensitivity, specificity, and
      precision were used as performance measures to compare the models. RESULTS: For
      the training dataset, the total observed accuracies of the decision tree, the
      random forest and boosted tree model were 70%, 69%, and 72% respectively. For the
      test dataset, the total observed accuracies were 71%, 53%, and 71% respectively.
      The boosted tree appeared to be the best for predicting a referral advice with a
      fair accuracy (Kappa between 0.2 and 0.4). Next to this, the measured evaluation
      measures show that all models provided a referral advice better than just a
      random guess. This means that all models learned some implicit knowledge of the
      provided referral advices in the training dataset. CONCLUSIONS: The study showed
      promising results on the possibility of using machine learning in the design of
      our CDSS. The boosted tree model performed best on the classification of low back
      pain cases, but still has to be improved. Therefore, new cases have to be
      collected, especially cases that are classified as self-care cases. This to be
      sure that also the self-care advice can be predicted well by the model.

PMID- 29331254
TI  - Technology alignment in the presence of regulatory changes: The case of
      meaningful use of information technology in healthcare.
AB  - OBJECTIVES: Using the context of the healthcare sector, this study examines the
      impact of regulatory change on technology implementation and use. Hospitals are
      now federally mandated to showcase meaningful use of information technology (IT).
      We theorize that IT plan scope structured prior to a regulatory change by means
      of a long-term planning horizon, top management involvement, and steering
      committee engagement impacts organizations' ability to fulfill meaningful use
      requirements three to five years later. Furthermore, we contend that this impact
      is contingent on the specific IT adoption strategy. METHODS: Data from the HIMSS
      and HITECH Act databases were combined to analyze 688 hospitals. Regression
      analyses were used to test the hypotheses. RESULTS: The results of this
      longitudinal study show that frequency of steering committee meetings and length
      of planning horizon broaden IT plan scope. Broader IT plan scope is positively
      associated with the ability of organizations to meaningfully use IT. CONCLUSIONS:
      The link between IT plan scope and meaningful use metric is particularly
      significant for organizations that adopt a more integrated approach towards IT
      adoption. Average reimbursement amount differences are provided and discussed
      between the different IT adoption strategies.

PMID- 29331255
TI  - An automated and robust image processing algorithm for glaucoma diagnosis from
      fundus images using novel blood vessel tracking and bend point detection.
AB  - Glaucoma is an ocular disease which can cause irreversible blindness. The disease
      is currently identified using specialized equipment operated by optometrists
      manually. The proposed work aims to provide an efficient imaging solution which
      can help in automating the process of Glaucoma diagnosis using computer vision
      techniques from digital fundus images. The proposed method segments the optic
      disc using a geometrical feature based strategic framework which improves the
      detection accuracy and makes the algorithm invariant to illumination and noise.
      Corner thresholding and point contour joining based novel methods are proposed to
      construct smooth contours of Optic Disc. Based on a clinical approach as used by
      ophthalmologist, the proposed algorithm tracks blood vessels inside the disc
      region and identifies the points at which first vessel bend from the optic disc
      boundary and connects them to obtain the contours of Optic Cup. The proposed
      method has been compared with the ground truth marked by the medical experts and
      the similarity parameters, used to determine the performance of the proposed
      method, have yield a high similarity of segmentation. The proposed method has
      achieved a macro-averaged f-score of 0.9485 and accuracy of 97.01% in correctly
      classifying fundus images. The proposed method is clinically significant and can
      be used for Glaucoma screening over a large population which will work in a real
      time.

PMID- 29331256
TI  - Measuring non-administration of ordered medications in the pediatric inpatient
      setting.
AB  - OBJECTIVE: Medication compliance in inpatient settings shows some significant
      gaps for adult patients. In pediatric settings prescribing and other
      administration errors have been studied but missed doses have not been
      specifically studied in the pediatric inpatient setting. We intended to apply
      health information technology and data processing methods to study the medication
      compliance for pediatric patients at our institution. STUDY DESIGN: We collected
      medication ordering, dispensing, and administration data spanning 42 months
      (7/1/2010 through 12/31/2013) for pediatric inpatients admitted to a major
      tertiary pediatric hospital. We analyzed the orders for which either the
      corresponding administration record was missing or the records indicated non
      administration. RESULTS: There were only 596 medication orders without
      corresponding administration records, accounting for less than 0.05% of 1.6
      Million orders for 56,000 patients. There were 40,999 orders with corresponding
      administration records indicating non-administration (or less than 3% of all
      orders). Overall order compliance of the nursing staff was 97.35%, with another
      2.6% of orders having a documented reason for non-administration The top two
      medication classes comprising the missed and non-administered orders were
      "Alimentary tract and metabolism drugs" and "Nervous system drugs". CONCLUSION:
      Measurement of medication compliance is an important quality measure of patient
      safety and quality of care. Our study found a small proportion of non
      administered medication orders and discovered corresponding reasons illustrating
      how health information technology can help to measure the quality of the
      medication process from ordering and dispensing to administration at a major
      healthcare institution.

PMID- 29331257
TI  - Service provision, pricing, and patient satisfaction in online health
      communities.
AB  - : Background The emergence of online health communities (OHCs) broadens and
      diversifies channels for patient-doctor interaction. In recent times, patient
      satisfaction has gained new attention within the context of OHCs where unique
      patterns are provided: a variety of services with unique attributes are available
      in OHCs for patients and doctors have the options of providing and pricing for
      different services. OHCs are given high hopes on improving medical efficiency and
      patient satisfaction. Knowing how these patterns in OHCs affect patient
      satisfaction is crucial for the development of OHCs and medical practices.
      METHODS: An empirical research is conducted to examine the effects of provision
      and pricing of online services on patient satisfaction by analyzing data from
      2309 doctors in a Chinese OHC. RESULTS: The results from this study provided
      empirical support, suggesting that service quantity positively influenced patient
      satisfaction. A non-linear correlation between service price and satisfaction was
      explored and results suggested an inverted U-shaped relationship. At the low
      price level, service price led to an increase in patient satisfaction, whereas
      the high price level (over 330 CNY/US$49) could have just the opposite effect.
      Importantly, we found that price difference between a doctor's different services
      significantly decreased patient satisfaction. A mediating effect was tested in
      post-hoc analyses, and results revealed that the impact of price difference on
      patient satisfaction was partially mediated by flexibility of service selection,
      and the mediating effect accounted for 28.6% of the total effect. CONCLUSIONS:
      Our results indicate that patient satisfaction can be improved by effectively
      providing and pricing services in OHCs. Specifically, doctors can offer different
      type services and charge within a reasonable range.

PMID- 29331258
TI  - Clinician user involvement in the real world: Designing an electronic tool to
      improve interprofessional communication and collaboration in a hospital setting.
AB  - OBJECTIVES: User involvement is vital to the success of health information
      technology implementation. However, involving clinician users effectively and
      meaningfully in complex healthcare organizations remains challenging. The
      objective of this paper is to share our real-world experience of applying a
      variety of user involvement methods in the design and implementation of a
      clinical communication and collaboration platform aimed at facilitating care of
      complex hospitalized patients by an interprofessional team of clinicians.
      METHODS: We designed and implemented an electronic clinical communication and
      collaboration platform in a large community teaching hospital. The design team
      consisted of both technical and healthcare professionals. Agile software
      development methodology was used to facilitate rapid iterative design and user
      input. We involved clinician users at all stages of the development lifecycle
      using a variety of user-centered, user co-design, and participatory design
      methods. RESULTS: Thirty-six software releases were delivered over 24 months.
      User involvement has resulted in improvement in user interface design,
      identification of software defects, creation of new modules that facilitated
      workflow, and identification of necessary changes to the scope of the project
      early on. CONCLUSION: A variety of user involvement methods were complementary
      and benefited the design and implementation of a complex health IT solution.
      Combining these methods with agile software development methodology can turn
      designs into functioning clinical system to support iterative improvement.

PMID- 29331259
TI  - Public and physician's expectations and ethical concerns about electronic health
      record: Benefits outweigh risks except for information security.
AB  - INTRODUCTION: Electronic Health Record systems (EHRs) offer numerous benefits in
      health care but also pose certain risks. As we progress toward the implementation
      of EHRs, a more in-depth understanding of attitudes that influence overall levels
      of EHR support is required. OBJECTIVES: To record public and physicians'
      awareness, expectations for, and ethical concerns about the use of EHRs. METHODS:
      A convenience sample was surveyed for both the public and physicians. The
      Public's Questionnaire was distributed to the public in a printed and an online
      version. The Physicians' Questionnaire was distributed to physicians in an online
      version. The questionnaires requested demographic characteristics followed by
      close-ended questions enquiring about awareness, perceived impact, perceived
      risks, and ethical issues raised by EHR use. RESULTS: In total, 46% of the public
      and 91% of physicians were aware of EHRs. Physicians' and public opinions were
      comparable concerning the positive impact of EHRs on better, more effective, and
      faster decisions on the patients' health, on better coordination between
      hospitals/clinics and on quality and reduced cost of health care. However,
      physicians were concerned that an EHR system would be a burden for their
      finances, for their time concerning training on the system, for their everyday
      workload and workflow. The majority of the public generally agreed that they
      would worry about the possibility that a non-authorized, third party might gain
      access to their personal health information (48.8%), and that they would worry
      about future discriminations due to possible disclosure of their health
      information (48.8%). Most physicians disagreed that EHRs will disrupt the doctor
      patient relationship (58.1%) but they would worry about the safety of their
      patients' information (53.1%). Overall, both the public and physicians were in
      favor of the implementation of an EHR system, evaluating that possible benefits
      are more important than possible risks. The majority of the public believed that
      physicians should have full access to an EHR (90.9%), whereas nursing staff,
      pharmacists, laboratory staff, and other healthcare professional should have
      partial access. CONCLUSIONS: The factors identified in the present study present
      actionable insights that may increase awareness about EHRs. The survey
      illustrates that both the public and physicians acknowledge the benefits and
      support EHRs on the condition that sufficient guarantees are provided about
      privacy and security.

PMID- 29331261
TI  - Necrotizing Granulomatous Inflammation with Airway Tissue Destruction.

PMID- 29331260
TI  - Multifaceted behavior of Meckel's diverticulum in children.
AB  - PURPOSE/BACKGROUND: Meckel's diverticulum (MD) is one of the most common
      congenital malformations of gastrointestinal tract in children. However, the
      nonspecific clinical manifestations of MD often cause a diagnostic as well as
      therapeutic challenge to pediatric surgeon. This study aimed to review our
      experience in managing this disease while evaluating the management strategies.
      METHODS: We retrospectively analyzed the clinical data of all patients diagnosed
      with MD admitted to our center between January 2010 and December 2015. Factors
      documented including demographic criteria, clinical manifestations, preoperative
      examinations, surgical methods, histopathological characteristics, postoperative
      complications, and outcomes. RESULTS: The patients included 210 males and 76
      females, aged from 1day to 15years. In fifty three patients, the MD was an
      incidental finding at laparotomy or laparoscopy. The remaining 233 patients were
      symptomatic and presented with various clinical features. Ninety nine patients
      presented with episodes of bleeding per rectum or melena. Fifty six patients
      demonstrated symptoms of diverticulitis or perforated MD. Forty patients were
      diagnosed as intestinal obstruction, and 35 patients with intussusception
      requiring surgical reduction. Two cases of Littre hernia and one case of foreign
      body trapped in MD were also observed in this group. Six patients misdiagnosed as
      appendicitis at another institution were reoperated in our department. Among the
      99 patients with bleeding per rectum, 78 underwent a Tc-99m scan that showed a
      positive tracer in 55 patients and negative in 23. All patients underwent
      resection of the diverticulum, except for 2 cases of postponed resection.
      Histology revealed ectopic gastric mucosa or ectopic pancreatic tissue in 154
      patients; significant differences were observed between the symptomatic group and
      the accidentally found group. One patient died of peritonitis and sepsis
      postoperatively; one case of anastomotic leak and one case of adhesive intestinal
      obstruction were reoperated. CONCLUSION: Meckel's diverticulum has various
      clinical presentations and it is difficult to make a precise diagnosis
      preoperatively. It is necessary to maintain a high suspicion of MD in the
      pediatric age group with symptoms of abdominal pain, gastrointestinal hemorrhage
      or intestinal obstruction. Heterotopic tissue is the main cause of complicated
      diverticulum, and it is safe and feasible to remove the incidentally found MD.
      Laparoscopy should become the first choice of methods in diagnosis and treatment
      of MD. TYPE OF STUDY: Treatment study. LEVEL OF EVIDENCE: Level IV.

PMID- 29331262
TI  - Can Interrogation of Tumour Characteristics Lead us to Safely Omit Adjuvant
      Radiotherapy in Patients with Early Breast Cancer?
AB  - Adjuvant radiotherapy after breast-conserving surgery has been an important
      component of the standard of care for early breast cancer. Improvements in breast
      cancer care have resulted in a substantial reduction in local relapse rates over
      recent decades. Although the proportional benefits of adjuvant radiotherapy are
      similar for different prognostic risk groups of patients, the absolute benefits
      depend on the risk of relapse and therefore vary considerably between prognostic
      groups. Radiotherapy is not without risk and for some patients at very low risk
      of relapse the risks of radiotherapy may outweigh the benefit, leading to
      potential overtreatment. Randomised controlled trial (RCT) evidence shows that
      omission of radiotherapy in low risk early breast cancer does not reduce overall
      survival or increase breast cancer mortality and local recurrences are
      salvageable. Despite this there has not been a change in practice regarding
      omission of radiotherapy. The reasons for this may include challenges in patient
      selection. Recent advances in immunohistochemistry and genomic profiling may
      improve risk stratification and the development of biomarkers to directed
      therapies. Several RCTs have quantified the benefit of radiotherapy in reducing
      local relapse. Where a treatment benefit is known but is considered to be so
      small not to be clinically relevant then alternatives to RCTs may be considered
      to answer the question of need. This is because we can assess risk against a
      fixed 'absolute' boundary rather than needing a randomised comparator. The
      prospective cohort study is an alternative to the RCT design to answer the
      question of need for radiotherapy. The feasibility of recruitment into biomarker
      directed de-escalation studies will become apparent as more studies open. The
      challenge is to determine if we are able to accurately risk stratify patients and
      avoid unnecessary toxicity, thereby tailoring the need for adjuvant breast
      radiotherapy on an individual patient basis.

PMID- 29331263
TI  - Glial scars are permeable to the neurotoxic environment of chronic stroke
      infarcts.
AB  - Following stroke, the damaged tissue undergoes liquefactive necrosis, a stage of
      infarct resolution that lasts for months although the exact length of time is
      currently unknown. One method of repair involves reactive astrocytes and
      microglia forming a glial scar to compartmentalize the area of liquefactive
      necrosis from the rest of the brain. The formation of the glial scar is a
      critical component of the healing response to stroke, as well as other central
      nervous system (CNS) injuries. The goal of this study was to evaluate the
      toxicity of the extracellular fluid present in areas of liquefactive necrosis and
      determine how effectively it is segregated from the remainder of the brain. To
      accomplish this goal, we used a mouse model of stroke in conjunction with an
      extracellular fluid toxicity assay, fluorescent and electron microscopy,
      immunostaining, tracer injections into the infarct, and multiplex immunoassays.
      We confirmed that the extracellular fluid present in areas of liquefactive
      necrosis following stroke is toxic to primary cortical and hippocampal neurons
      for at least 7 weeks following stroke, and discovered that although glial scars
      are robust physical and endocytic barriers, they are nevertheless permeable. We
      found that molecules present in the area of liquefactive necrosis can leak across
      the glial scar and are removed by a combination of paravascular clearance and
      microglial endocytosis in the adjacent tissue. Despite these mechanisms, there is
      delayed atrophy, cytotoxic edema, and neuron loss in regions adjacent to the
      infarct for weeks following stroke. These findings suggest that one mechanism of
      neurodegeneration following stroke is the failure of glial scars to impermeably
      segregate areas of liquefactive necrosis from surviving brain tissue.

PMID- 29331264
TI  - Altered levels of the splicing factor muscleblind modifies cerebral cortical
      function in mouse models of myotonic dystrophy.
AB  - Myotonic dystrophy (DM) is a progressive, multisystem disorder affecting skeletal
      muscle, heart, and central nervous system. In both DM1 and DM2, microsatellite
      expansions of CUG and CCUG RNA repeats, respectively, accumulate and disrupt
      functions of alternative splicing factors, including muscleblind (MBNL) proteins.
      Grey matter loss and white matter changes, including the corpus callosum, likely
      underlie cognitive and executive function deficits in DM patients. However,
      little is known how cerebral cortical circuitry changes in DM. Here, flavoprotein
      optical imaging was used to assess local and contralateral responses to
      intracortical motor cortex stimulation in DM-related mouse models. In control
      mice, brief train stimulation generated ipsilateral and contralateral homotopic
      fluorescence increases, the latter mediated by the corpus callosum. Single pulse
      stimulation produced an excitatory response with an inhibitory-like surround
      response mediated by GABAA receptors. In a mouse model of DM2 (Mbnl2 KO), we
      observed prolonged and increased responsiveness to train stimulation and loss of
      the inhibition from single pulse stimulation. Conversely, mice overexpressing
      human MBNL1 (MBNL1-OE) exhibited decreased contralateral response to train
      stimulation and reduction of inhibitory-like surround to single pulse
      stimulation. Therefore, altering levels of two key DM-associated splicing factors
      modifies functions of local cortical circuits and contralateral responses
      mediated through the corpus callosum.

PMID- 29331266
TI  - Human papilloma virus-specific T cells can be generated from naive T cells for
      use as an immunotherapeutic strategy for immunocompromised patients.
AB  - Human papilloma virus (HPV) is a known cause of cervical cancer, squamous cell
      carcinoma and laryngeal cancer. Although treatments exist for HPV-associated
      malignancies, patients unresponsive to these therapies have a poor prognosis.
      Recent findings from vaccine studies suggest that T-cell immunity is essential
      for disease control. Because Epstein-Barr Virus (EBV)-specific T cells have been
      highly successful in treating or preventing EBV-associated tumors, we
      hypothesized that the development of a manufacturing platform for HPV-specific T
      cells from healthy donors could be used in a third-party setting to treat
      patients with high-risk/relapsed HPV-associated cancers. Most protocols for
      generating virus-specific T cells require prior exposure of the donor to the
      targeted virus and, because the seroprevalence of high-risk HPV types varies
      greatly by age and ethnicity, manufacturing of donor-derived HPV-specific T cells
      has proven challenging. We, therefore, made systematic changes to our current
      Good Manufacturing Practice (GMP)-compliant protocols to improve antigen
      presentation, priming and expansion for the manufacture of high-efficacy HPV
      specific T cells. Like others, we found that current methodologies fail to expand
      HPV-specific T cells from most healthy donors. By optimizing dendritic cell
      maturation and function with lipopolysaccharide (LPS) and interferon (IFN)gamma,
      adding interleukin (IL)-21 during priming and depleting memory T cells, we
      achieved reliable expansion of T cells specific for oncoproteins E6 and E7 to
      clinically relevant amounts (mean, 578-fold expansion; n = 10), which were
      polyfunctional based on cytokine multiplex analysis. In the third-party setting,
      such HPV-specific T-cell products might serve as a potent salvage therapy for
      patients with HPV-associated diseases.

PMID- 29331265
TI  - Mechanisms of Memory Disruption in Depression.
AB  - Depressed individuals typically show poor memory for positive events, potentiated
      memory for negative events, and impaired recollection. These phenomena are
      clinically important but poorly understood. Compelling links between stress and
      depression suggest promising candidate mechanisms. Stress can suppress
      hippocampal neurogenesis, inhibit dopamine neurons, and sensitize the amygdala.
      We argue that these phenomena may impair pattern separation, disrupt the encoding
      of positive experiences, and bias retrieval toward negative events, respectively,
      thus recapitulating core aspects of memory disruption in depression.
      Encouragingly, optogenetic reactivation of cells engaged during the encoding of
      positive memories rapidly reduces depressive behavior in preclinical models.
      Thus, many memory deficits in depression appear to be downstream consequences of
      chronic stress, and addressing memory disruption can have therapeutic value.

PMID- 29331267
TI  - Identification and initial optimization of inhibitors of Clostridium difficile
      (C. difficile) toxin B (TcdB).
AB  - The discovery, synthesis and preliminary structure-activity relationship (SAR) of
      a novel class of inhibitors of Clostridium difficile (C. difficile) toxin B
      (TcdB) is described. A high throughput screening (HTS) campaign resulted in the
      identification of moderately active screening hits 1-5 the most potent of which
      was compound 1 (IC50 = 0.77 uM). In silico docking of an early analog offered
      suggestions for structural modification which resulted in the design and
      synthesis of highly potent analogs 13j(IC50 = 1 nM) and 13 l(IC50 = 7 nM) which
      were chosen as leads for further optimization.

PMID- 29331268
TI  - The Population Biology and Transmission Dynamics of Loa loa.
AB  - Endemic to Central Africa, loiasis - or African eye worm (caused by the filarial
      nematode Loa loa) - affects more than 10 million people. Despite causing ocular
      and systemic symptoms, it has typically been considered a benign condition, only
      of public health relevance because it impedes mass drug administration-based
      interventions against onchocerciasis and lymphatic filariasis in co-endemic
      areas. Recent research has challenged this conception, demonstrating excess
      mortality associated with high levels of infection, implying that loiasis
      warrants attention as an intrinsic public health problem. This review summarises
      available information on the key parasitological, entomological, and
      epidemiological characteristics of the infection and argues for the mobilisation
      of resources to control the disease, and the development of a mathematical
      transmission model to guide deployment of interventions.

PMID- 29331269
TI  - Clinical benefits of autologous haematopoietic stem cell transplantation in type
      1 diabetes patients.
AB  - : Type 1 diabetes (T1D) is characterized by severe damage to pancreas islet
      function through immunological attack; therefore, it is also called 'insulin
      dependent diabetes'. The present study aimed to evaluate the safety and clinical
      efficacy of autologous haematopoietic stem cell transplantation (AHSCT) in
      adolescent patients with newly diagnosed T1D. A phase-II prospective, parallel
      assignment, non-randomized trial was conducted from March 2008 to December 2011
      with 40 T1D patients, of whom 20 received AHSCT therapy and 20 were treated only
      with insulin injections. Of these patients, 14 (70%) in the AHSCT group became
      insulin-independent for 1.5 to 48 months compared with only one patient in the
      Insulin group. Of these 14 AHSCT patients, 11 relapsed within a median time of
      19.5 (range 5.5-1) months and resumed insulin use. By the end of the 4-year
      follow-up, the difference in daily insulin dosages between the AHSCT and Insulin
      groups had become smaller (0.49+/-0.32IU/kg/day vs. 0.79+/-0.18IU/kg/day,
      respectively; P<0.01). C-peptide levels increased significantly at 3 months in
      both groups and later decreased, with the insulin group showing more rapid
      deterioration. Most of the adverse events in the AHSCT group were transplantation
      complications. Our data suggest that AHSCT treatment was well tolerated and
      slowed deterioration of islet beta-cell function while significantly decreasing
      daily insulin dosages. However, because of the high relapse rate, more
      information on longer-term outcomes is needed before AHSCT can be routinely
      considered for T1D patients. SIGNIFICANCE: although this was a non-randomized
      clinical study, this phase-II trial demonstrated the beneficial effects of AHSCT
      in patients with newly diagnosed T1D by increasing C-peptide levels and inducing
      insulin independence, while showing its safety and good tolerability compared
      with conventional intensive insulin therapy. Thus, these results are helpful for
      increasing our understanding of the use of haematopoietic stem cell therapy in
      the treatment of T1D and for evaluating whether it can become more widespread in
      future.

PMID- 29331271
TI  - The durability of operational improvements with rotational patient assignment.
AB  - INTRODUCTION: Previous work has suggested that Emergency Department rotational
      patient assignment (a system in which patients are algorithmically assigned to
      physicians) is associated with immediate (first-year) improvements in operational
      metrics. We sought to determine if these improvements persisted over a longer
      follow-up period. METHODS: Single-site, retrospective analysis focused on years 2
      4 post-implementation (follow-up) of a rotational patient assignment system. We
      compared operational data for these years with previously published data from the
      last year of physician self-assignment and the first year of rotational patient
      assignment. We report data for patient characteristics, departmental
      characteristics and facility characteristics, as well as outcomes of length of
      stay (LOS), arrival to provider time (APT), and rate of patients who left before
      being seen (LBBS). RESULTS: There were 140,673 patient visits during the five
      year period; 138,501 (98.7%) were eligible for analysis. LOS, APT, and LBBS
      during follow-up remained improved vs. physician self-assignment, with
      improvements similar to those noted in the first year of implementation. Compared
      with the last year of physician self-assignment, approximate yearly average
      improvements during follow-up were a decrease in median LOS of 18min (8%
      improvement), a decrease in median APT of 21min (54% improvement), and a decrease
      in LBBS of 0.69% (72% improvement). CONCLUSION: In a single facility study,
      rotational patient assignment was associated with sustained operational
      improvements several years after implementation. These findings provide further
      evidence that rotational patient assignment is a viable strategy in front-end
      process redesign.

PMID- 29331270
TI  - Severe beta blocker and calcium channel blocker overdose: Role of high dose
      insulin.
AB  - A 54-year-old female presented after taking an overdose of an unknown amount of
      hydrochlorothiazide, doxazocin, atenolol and amlodipine. She was initially
      refractory to treatment with conventional therapy (intravenous fluids, activated
      charcoal, glucagon 5 mg followed with glucagon drip, calcium gluconate 10%, and
      atropine). Furthermore, insulin at 4 U/kg was not effective in improving her
      hemodynamics. Shortly after high dose insulin was achieved with 10 U/kg, there
      was dramatic improvement in hemodynamics resulting in three of five vasopressors
      being weaned off in 8 h. She was subsequently off all vasopressors after six
      additional hours. The role of high dose insulin has been documented in prior
      cases, however it is generally recommended after other conventional therapies
      have failed. However, there are other reports that suggest it as initial therapy.
      Our patient failed conventional therapies and responded well only with maximum
      dose of insulin. Physicians should consider high dose insulin early in severe
      beta blocker or calcium channel blocker overdose for improvement in hemodynamics.
      This leads to early discontinuation of vasopressors. It is important that
      emergency physicians be aware of the beneficial effects of high dose insulin when
      initiated early as opposed to waiting for conventional therapy to fail; as these
      patients often present first to the emergency department. Early initiation in the
      emergency department can be beneficial in these patients.

PMID- 29331272
TI  - High-Sensitivity Cardiac Troponin and New-Onset Heart Failure: A Systematic
      Review and Meta-Analysis of 67,063 Patients With 4,165 Incident Heart Failure
      Events.
AB  - OBJECTIVES: The aim of this study was to systematically collate and appraise the
      available evidence regarding the association between high-sensitivity cardiac
      troponin (hs-cTn) and incident heart failure (HF) and the added value of hs-cTn
      in HF prediction. BACKGROUND: Identification of subjects at high risk for HF and
      early risk factor modification with medications such as angiotensin-converting
      enzyme inhibitors may delay the onset of HF. Hs-cTn has been suggested as a
      prognostic marker for the incidence of first-ever HF in asymptomatic subjects.
      METHODS: PubMed, Embase, and Web of Science were systematically searched for
      prospective cohort studies published before January 2017 that reported
      associations between hs-cTn and incident HF in subjects without baseline HF.
      Study-specific multivariate-adjusted hazard ratios (HRs) were pooled using random
      effects meta-analysis. RESULTS: Data were collated from 16 studies with a total
      of 67,063 subjects and 4,165 incident HF events. The average age was 57 years,
      and 47% were women. Study quality was high (Newcastle-Ottawa score 8.2 of 9). In
      a comparison of participants in the top third with those in the bottom third of
      baseline values of hs-cTn, the pooled multivariate-adjusted HR for incident HF
      was 2.09 (95% confidence interval [CI]: 1.76 to 2.48; p < 0.001). Between-study
      heterogeneity was high, with an I2 value of 80%. HRs were similar in men and
      women (2.29 [95% CI: 1.64 to 3.21] vs. 2.18 [95% CI: 1.68 to 2.81]) and for hs
      cTnI and hs-cTnT (2.09 [95% CI: 1.53 to 2.85] vs. 2.11 [95% CI: 1.69 to 2.63])
      and across other study-level characteristics. Further adjustment for B-type
      natriuretic peptide yielded a similar HR of 2.08 (95% CI: 1.64 to 2.65). Assay of
      hs-cTn in addition to conventional risk factors provided improvements in the C
      index of 1% to 3%. CONCLUSIONS: Available prospective studies indicate a strong
      association of hs-cTn with the risk of first-ever HF and significant improvements
      in HF prediction.

PMID- 29331273
TI  - Meta-Analyses and Interpretation of Troponin Values in Heart Failure.

PMID- 29331274
TI  - Clinical outcomes of endoscopic submucosal dissection for large colorectal
      laterally spreading tumors in older adults.
AB  - BACKGROUND AND AIMS: The colorectal endoscopic submucosal dissection (ESD)
      remains technically challenging, especially for older patients who frequently
      encounter complex chronic diseases and have a loose colon. However, only limited
      number of studies are available for the safety of ESD in older patients with
      especially large laterally spreading tumors. Therefore, in this retrospective
      study, we compared the outcomes of ESD for laterally spreading tumors (LST)
      >=3cm(cm) in older patients to that in younger patients. METHODS: Consecutive
      patients with LSTs 3cm or larger were enrolled for from May 2010-2016. These
      patients were divided into two groups: the younger group (<65years) and the older
      group (>=65years). The clinicopathologic findings and the outcomes of ESD
      procedures were compared between the two groups. RESULTS: A total of 70 patients
      in the younger group and 73 patients in the older group were treated by ESD for
      colorectal LSTs larger than 3cm. No significant differences were observed in the
      gender ratio, tumor morphological type, tumor location, and tumor size between
      the two groups. The en bloc resection rates were 85.7 and 89.0%, respectively,
      without a significant difference. The procedural time was similar between the
      younger and older patients (71.8+/-34.7min vs. 70.6+/-29.5min). The duration of
      hospital stay was not significantly different between the two groups (4.1+/
      2.2days vs. 4.4+/-2.5days). No significant differences were observed between the
      two groups with respect to ESD-related complications including delayed bleeding,
      perforation, and stricture. CONCLUSIONS: ESD appears to be an effective and safe
      method for LSTs larger than 3cm in older patients.

PMID- 29331275
TI  - Low-level cadmium exposure and cardiovascular outcomes in elderly Australian
      women: A cohort study.
AB  - BACKGROUND: Cadmium has been associated with increased risk of cardiovascular
      disease (CVD) in observational studies, however there has been a limited focus on
      this relationship in women. OBJECTIVES: This study investigated the association
      of urinary cadmium (UCd) concentrations with CVD outcomes and all-cause mortality
      in elderly Western Australian (WA) women. METHODS: UCd excretion was measured at
      baseline in 1359 women, mean age 75.2 +/- 2.7 years and 14.5 years of
      atherosclerotic vascular disease (ASVD) hospitalisations and deaths, including
      both the principle cause of death and all associated causes of death. Health
      outcome data were retrieved from the Western Australian Data Linkage System. Cox
      regression analysis was used to estimate hazard ratios of ASVD and all-cause
      mortality. UCd was ln-transformed and models were adjusted for demographic and
      CVD risk factors. RESULTS: Median (IQR) concentration of UCd was 0.18 (0.09-0.32)
      MUg/L. In multivariable-adjusted analyses per ln unit (equivalent to ~2.7 fold)
      increase in UCd, there was a 36% increase in the risk of death from heart failure
      and 17% increase in the risk of a heart failure event, respectively (HR = 1.36,
      95% CI 1.11-1.67; HR = 1.17, 95% CI 1.01-1.35). When analyses were restricted to
      never smokers the relationship between UCd and death from heart failure remained
      (HR 1.29, 95% CI 1.01-1.63). CONCLUSIONS: This study suggests that even at low
      levels of exposure cadmium may be associated with heart failure hospitalisations
      and deaths in older women, however given the dilute nature of these urine
      samples, the results must be interpreted with caution.

PMID- 29331276
TI  - Analyzing recommender systems for health promotion using a multidisciplinary
      taxonomy: A scoping review.
AB  - BACKGROUND: Recommender systems are information retrieval systems that provide
      users with relevant items (e.g., through messages). Despite their extensive use
      in the e-commerce and leisure domains, their application in healthcare is still
      in its infancy. These systems may be used to create tailored health
      interventions, thus reducing the cost of healthcare and fostering a healthier
      lifestyle in the population. OBJECTIVE: This paper identifies, categorizes, and
      analyzes the existing knowledge in terms of the literature published over the
      past 10 years on the use of health recommender systems for patient interventions.
      The aim of this study is to understand the scientific evidence generated about
      health recommender systems, to identify any gaps in this field to achieve the
      United Nations Sustainable Development Goal 3 (SDG3) (namely, "Ensure healthy
      lives and promote well-being for all at all ages"), and to suggest possible
      reasons for these gaps as well as to propose some solutions. METHODS: We
      conducted a scoping review, which consisted of a keyword search of the literature
      related to health recommender systems for patients in the following databases:
      ScienceDirect, PsycInfo, Association for Computing Machinery, IEEExplore, and
      Pubmed. Further, we limited our search to consider only English-language journal
      articles published in the last 10 years. The reviewing process comprised three
      researchers who filtered the results simultaneously. The quantitative synthesis
      was conducted in parallel by two researchers, who classified each paper in terms
      of four aspects-the domain, the methodological and procedural aspects, the health
      promotion theoretical factors and behavior change theories, and the technical
      aspects-using a new multidisciplinary taxonomy. RESULTS: Nineteen papers met the
      inclusion criteria and were included in the data analysis, for which thirty-three
      features were assessed. The nine features associated with the health promotion
      theoretical factors and behavior change theories were not observed in any of the
      selected studies, did not use principles of tailoring, and did not assess (cost)
      effectiveness. DISCUSSION: Health recommender systems may be further improved by
      using relevant behavior change strategies and by implementing essential
      characteristics of tailored interventions. In addition, many of the features
      required to assess each of the domain aspects, the methodological and procedural
      aspects, and technical aspects were not reported in the studies. CONCLUSIONS: The
      studies analyzed presented few evidence in support of the positive effects of
      using health recommender systems in terms of cost-effectiveness and patient
      health outcomes. This is why future studies should ensure that all the proposed
      features are covered in our multidisciplinary taxonomy, including integration
      with electronic health records and the incorporation of health promotion
      theoretical factors and behavior change theories. This will render those studies
      more useful for policymakers since they will cover all aspects needed to
      determine their impact toward meeting SDG3.

PMID- 29331277
TI  - Unplanned reoperation after hepatectomy: an analysis of risk factors and
      outcomes.
AB  - BACKGROUND/PURPOSE: Reoperation is being increasingly utilized as a metric for
      surgical care quality. The aim of this study was to identify the incidence of and
      risk factors for unplanned reoperation following index hepatectomy. METHODS: Pre,
      intra- and post-operative information of patients who underwent partial
      hepatectomy in 435 hospitals participating in the American College of Surgeons
      National Surgical Quality Improvement Program from 2011 to 2013 were analyzed.
      RESULTS: 343 (4%) of 9195 patients required reoperation within 30 days of index
      hepatectomy. The index procedures with the highest incidence of reoperation (%)
      were trisectionectomy (7%) and right hepatectomy (5%). Patients who underwent
      reoperation had increased index operative duration (323 +/- 174 min versus 243 +/
      125 min, p < 0.001), postoperative transfusion (57% versus 23%, p < 0.001),
      wound complications, cardiorespiratory, renal, thromboembolic, and infectious
      events. Hemorrhage was the most common indication for reoperation (10%). Male
      gender, ASA class 4, and right hepatectomy or trisectionectomy were independent
      predictors of reoperation (OR 1.4 [1.1-1.7], p = 0.007; 2.0 [1.3-3.1], p = 0.003;
      1.6 [1.2-2.0], p = 0.001 and 2.5 [1.8-3.4], p < 0.001, respectively). All
      reoperations occurred during index hospitalization and resulted in longer mean
      length of stay (19 +/- 17 days versus 7 +/- 7 days, p < 0.001). CONCLUSION:
      Reoperation is associated with several patient characteristics and procedural
      factors in this national sample. Knowledge of these factors can increase
      awareness of patients at risk for reoperation.

PMID- 29331278
TI  - Impact of treatment with a Protein Tyrosine Kinase Inhibitor (Genistein) on acute
      and chronic experimental Schistosoma mansoni infection.
AB  - Schistosomiasis mansoni is considered one of the most common fibrotic diseases
      resulting from inflammation and deposition of fibrous tissue around parasitic
      eggs trapped in the liver, causing morbidity and mortality. Chemotherapy against
      schistosomiasis is largely dependent on Praziquantel (PZQ). Yet, the huge
      administration of it in endemic areas and its incompetence towards the immature
      stages have raised serious alarms against the development of drug resistance. Few
      drugs are directed to reverse schistosomal liver fibrosis, particularly at the
      chronic and advanced stages of the disease. Recently, protein tyrosine kinase
      (PTK) inhibitors have been identified as potent anti-schistosomal and anti
      fibrotic drugs against schistosomes, that may suppress and reverse Schistosoma
      mansoni (S. mansoni) induced liver fibrosis. The present study was designed to
      assess the anti-schistosomal and antifibrotic activity of Genistein, a PTK
      inhibitor, in comparison to PZQ, on both acute and chronic S. mansoni-infected
      mice using different parasitological, histopathological and immunohistochemical
      studies. Genistein showed a significant reduction (P < .05) in total worm burden,
      tissue egg load, mean hepatic granulomas diameter and numbers, percentage of
      collagen and expression of transforming growth factor-beta 1 (TGF-beta 1) in the
      examined hepatocytes with elevation in percentage of degenerated ova, in
      comparison to the control groups, in both acute and chronic stages of infection.
      The best results were obtained when Genistein was combined with PZQ. Therefore,
      it was concluded that Genistein showed a promising anti-schistosomal and anti
      fibrotic properties which could make it one of the new potential targets in
      chemotherapy against schistosomiasis.

PMID- 29331279
TI  - Dynamics of spatiotemporal distribution of schistosomiasis in Hubei Province,
      China.
AB  - Schistosomiasis caused by parasitic flatworms of blood flukes, remains a major
      public health concern in China. The significant progress in controlling
      schistosomiasis in China over the past decades has resulted in the remarkable
      reduction in the prevalence and intensity of Schistosoma japonicum infection to
      an extremely low level. Therefore, the elimination of schistosomiasis has been
      promoted by the Chinese national government. Hubei Province is the major endemic
      area, that is, along the middle and low reaches of the Yangtze River in the lake
      and marshland regions of southern China. Eliminating the transmission of
      schistosomiasis in Hubei Province is challenging. The current issue is to
      determine the distributions and clusters of schistosomiasis transmission. In this
      study, we assessed the spatial distribution of schistosomiasis and the risk at
      the county level in Hubei Province from 2011 to 2015 to provide guidance on the
      elimination of schistosomiasis transmission in lake and marshland regions.
      Spatial database of human S.japonicum infection from 2011 to 2015 at the county
      level in the study area was built based on the annual schistosomias is
      surveillance data. Moran's I, the global spatial autocorrelation statistics, was
      utilized to describe the spatial autocorrelation of human S. japonicum infection.
      In addition, purely spatial scan statistics combined with space-time scan
      statistics were used to determine the epidemic clusters. Infection rates of S.
      japonicum decreased in each endemic county in Hubei from 2011 to 2015. Human S.
      japonicum infection rate showed statistical significance by global
      autocorrelation analysis during the study period (Moran's I > 0, P < 0.01). This
      result suggested that there were spatial clusters present in the distribution of
      S. japonicum infection for the five years. Purely spatial analysis of human S.
      japonicum infection showed one most likely cluster and one secondary cluster from
      2011 to 2015, which covered four and one counties, respectively. Spatiotemporal
      clustering analysis determined one most likely cluster and one secondary cluster
      both in 2011-2012, which appeared in 4 and 5 counties, respectively. However, the
      number of clustering foci decreased with time, and no cluster was detected after
      2013.The clustering foci were both located at the Jianghan Plain, along the
      middle reaches of the Yangtze River and its connecting branch Hanbei River.
      Spatial distribution of human S. japonicum infections did not change temporally
      at the county level in Hubei Province. A declining trend in spatiotemporal
      clustering was observed between 2011 and 2015. However, effective control
      strategies and integrated prevention should be continuously performed, especially
      at the Jianghan Plain area along the Yangtze and Hanbei River Basin. Multivariate
      statistical analysis was carried out to investigate the risk of missing
      examinations, missing treatment, and unstandardized treatment events. The results
      showed that age, education level and Sanitary latrines are risk factors for
      missing examinations (b > 0, OR >1), and treatment times in past and feeding
      cattle in village group are protective factors (b < 0, OR <1). We also found that
      age and education level are risk factors for missing treatment (b > 0, OR >1).
      Study of the risk for un-standardized treatment revealed that occupation is risk
      factors (b > 0, OR >1), though, education level is protective factors (b < 0, OR
      <1). Therefore, precise prevention and control should be mainly targeted at these
      special populations.

PMID- 29331280
TI  - [Jurisdictions on the reimbursement of new medical technologies by public health
      insurance: A systematic review].
AB  - BACKGROUND: In Germany reimbursement for new medical technologies is often
      enforced before a social court. It is likely that these judicial decisions also
      affect the sickness funds' decisions on requests for reimbursement and thus
      patient access to new technologies in general. OBJECTIVES: The aim of this study
      was to identify the technologies that have repeatedly generated court actions and
      whether these actions have been successful. The focus was on differences between
      sectors, technology groups and indications. Based on this, we analysed in a case
      study whether judicial decisions on the reimbursement of the same technologies
      vary across the years. MATERIAL AND METHODS: Based on a systematic review, we
      identified judicial decisions of German social courts on new technologies for the
      years 2011 to 2016. The analysis included social court decisions on
      reimbursements for technologies used in the treatment of individual patients.
      RESULTS: 284 judicial decisions on new technologies were considered in the
      analysis. In one third of the cases, the sickness funds were required to
      reimburse the costs, with a higher percentage in inpatient than in outpatient
      care. Technologies used in treatment of diseases of the eyes and the ears were
      granted most frequently. In cases involving similar circumstances the social
      courts sometimes came to conflicting decisions; these decisions are, in part,
      contradictory to subsequent assessments by the Joint Federal Committee (G-BA).
      CONCLUSIONS: Decisions as to whether reimbursement for new technologies is
      granted or not do not appear to follow a systematic approach. In the context of
      the seemingly innovation-friendly policy in inpatient care, there is uncertainty
      with regard to the "generally accepted state of medical knowledge." It is
      problematic for both patients and their treating physicians that over a number of
      years legal proceedings are being initiated for technologies that have not been
      subjected to a systematic assessment of their benefit.

PMID- 29331281
TI  - [Do online ratings reflect structural differences in healthcare? The example of
      German physician-rating websites].
AB  - BACKGROUND: Previous surveys have shown that patient satisfaction varies with the
      regional supply of physicians. Online ratings on physician-rating websites
      represent a relatively new instrument to display patient satisfaction results.
      The aim of this study was (1) to assess the current state of online ratings for
      two medical disciplines (dermatologists and ear, nose and throat (ENT)
      specialists), and (2) to analyze online derived patient satisfaction results
      according to the physician density in Germany. METHODS: We collected online
      ratings for 420 dermatologists and 450 ear, nose, and throat (ENT) specialists on
      twelve German physician-rating websites. We analyzed the online ratings according
      to the physician density (low, medium, high physician density). For this purpose,
      we collected secondary data from both physician-rating websites and the regional
      associations of statutory health insurance physicians. Data analysis was
      performed using Median tests and Chi-square tests. RESULTS: In total, 10,239
      online ratings for dermatologists and 8,168 online ratings for ENT specialists
      were analyzed. Almost all dermatologists (99.3 %) and ENT specialists (98.9 %)
      were listed on one of the physician-rating websites. A total of 93.5 % of all
      listed dermatologists and 96.9 % of ENT-specialists were rated on at least one of
      the physician-rating websites. Significant differences were found in the
      distribution (i.e., percentage of listed or rated physicians) of the ratings
      according to the regional physician density on only one physician-rating website
      (p<0.001). Furthermore, online ratings were shown to be better in regions with a
      higher physician density on two physician-rating website. On jameda.de, for
      example, dermatologist ratings were better in regions with a higher physician
      density compared to regions with a lower number of physicians (average rating:
      2.16 vs. 2.67; p<0.001). CONCLUSIONS: Online ratings of dermatologists and ENT
      specialists hardly differ in terms of regional physician density. Physician
      rating websites thus do not appear to be appropriate to mirror differences in the
      health service delivery structure. Our findings thus do not confirm the results
      from previously published studies.

PMID- 29331283
TI  - The influx of marine debris from the Great Japan Tsunami of 2011 to North
      American shorelines.
AB  - Marine debris is one of the leading threats to the ocean and the Great East Japan
      Earthquake and tsunami on March 11, 2011 washed away an estimated 5million tons
      of debris in a single, tragic event. Here we used shoreline surveys, disaster
      debris reports and ocean drift models to investigate the temporal and spatial
      trends in the arrival of tsunami marine debris. The increase in debris influx to
      surveyed North American and Hawaiian shorelines was substantial and significant,
      representing a 10 time increase over the baseline in northern Washington State
      where a long term dataset was available. The tsunami event brought different
      types of debris along the coast, with high-windage items dominant in Alaska and
      British Columbia and large, medium-windage items in Washington State and Oregon.
      Recorded cumulative debris landings to North America were close to 100,000 items
      in the four year study period. The temporal peaks in measured shoreline debris
      and debris reports match the ocean drift model solutions. Mitigation and
      monitoring activities, such as shoreline surveys, provide crucial data and
      monitoring for potential impacts should be continued in the future.

PMID- 29331282
TI  - Development, Testing, and Implementation of a Training Curriculum for
      Nonphysician Health Workers to Reduce Cardiovascular Disease.
AB  - BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death worldwide.
      The need to address CVD is greatest in low- and middle-income countries where
      there is a shortage of trained health workers in CVD detection, prevention, and
      control. OBJECTIVES: Based on the growing evidence that many elements of chronic
      disease management can be shifted to nonphysician health care workers (NPHW), the
      HOPE-4 (Heart Outcomes Prevention and Evaluation Program) aimed to develop, test,
      and implement a training curriculum on CVD prevention and control in Colombia,
      Malaysia, and low-resource settings in Canada. METHODS: Curriculum development
      followed an iterative and phased approach where evidence-based guidelines,
      revised blood pressure treatment algorithms, and culturally relevant risk factor
      counseling were incorporated. Through a pilot-training process with high school
      students in Canada, the curriculum was further refined. Implementation of the
      curriculum in Colombia, Malaysia, and Canada occurred through partner
      organizations as the HOPE-4 team coordinated the program from Hamilton, Ontario,
      Canada. In addition to content on the burden of disease, cardiovascular system
      pathophysiology, and CVD risk factors, the curriculum also included evaluations
      such as module tests, in-class exercises, and observed structured clinical
      examinations, which were administered by the local partner organizations. These
      evaluations served as indicators of adequate uptake of curriculum content as well
      as readiness to work as an NPHW in the field. RESULTS: Overall, 51 NPHW
      successfully completed the training curriculum with an average score of 93.19% on
      module tests and 84.76% on the observed structured clinical examinations. Since
      implementation, the curriculum has also been adapted to the World Health
      Organization's HEARTS Technical Package, which was launched in 2016 to improve
      management of CVD in primary health care. CONCLUSIONS: The robust curriculum
      development, testing, and implementation process described affirm that NPHW in
      diverse settings can be trained in implementing measures for CVD prevention and
      control.

PMID- 29331285
TI  - Reply.

PMID- 29331284
TI  - Effects of an experimental heat wave on fatty acid composition in two
      Mediterranean seagrass species.
AB  - Global warming is emerging as one of the most critical threats to terrestrial and
      marine species worldwide. This study assessed the effects of simulated warming
      events in culture on two seagrass species, Posidonia oceanica and Cymodocea
      nodosa, which play a key role in coastal ecosystems of the Mediterranean Sea.
      Changes in fatty acids as key metabolic indicators were assessed in specimens
      from two geographical populations of each species adapted to different in situ
      temperature regimes. Total fatty acid (TFA) content and composition were compared
      in C. nodosa and P. oceanica from natural populations and following exposure to
      heat stress in culture. After heat exposure, individuals of C. nodosa and P.
      oceanica adapted to colder temperatures in situ accumulated significantly more
      TFA than controls. For both species, the proportion of polyunsaturated fatty
      acids (PUFA) decreased, and the percentage of saturated fatty acids (SFA)
      increased significantly after the heat treatment. These results highlight that
      populations of both species living at warmest temperatures in situ were more
      thermo-tolerant and exhibited a greater capacity to cope with heat stress by
      readjusting their lipid composition faster. Finally, exposure of seagrasses to
      warmer conditions may induce a decrease in PUFA/SFA ratio which could negatively
      affect their nutritional value and generate important consequences in the healthy
      state of next trophic levels.

PMID- 29331286
TI  - Re: Characteristics of a Mild Traumatic Brain Injury Sample Recruited Using
      Amazon's Mechanical Turk.

PMID- 29331287
TI  - Characterizing the effects of deep brain stimulation with magnetoencephalography:
      A review.
AB  - BACKGROUND: Deep brain stimulation (DBS) is an important form of neuromodulation
      that is being applied to patients with motor, mood, or cognitive circuit
      disorders. Despite the efficacy and widespread use of DBS, the precise mechanisms
      by which it works remain unknown. Over the last decade, magnetoencephalography
      (MEG) has become an important functional neuroimaging technique used to study
      DBS. OBJECTIVE: This review summarizes the literature related to the use of MEG
      to characterize the effects of DBS. METHODS: Peer reviewed literature on DBS-MEG
      was obtained by searching the publicly accessible literature databases available
      on PubMed. The abstracts of all reports were scanned and publications which
      combined DBS-MEG in human subjects were selected for review. RESULTS: A total of
      32 publications met the selection criteria, and included studies which applied
      DBS for Parkinson's disease, dystonia, chronic pain, phantom limb pain, cluster
      headache, and epilepsy. DBS-MEG studies provided valuable insights into network
      connectivity, pathological coupling, and the modulatory effects of DBS.
      CONCLUSIONS: As DBS-MEG research continues to develop, we can expect to gain a
      better understanding of diverse pathophysiological networks and their response to
      DBS. This knowledge will improve treatment efficacy, reduce side-effects, reveal
      optimal surgical targets, and advance the development of closed-loop
      neuromodulation.

PMID- 29331288
TI  - Hallux Valgus Evaluation on MRI: Can Measurements Validated on Radiographs Be
      Used?
AB  - Hallux valgus (HV) is a common deformity of the great toe affecting >23% of
      adults in the United States. The severity of the deformity is traditionally
      analyzed using radiographs to determine measurements such as the HV and
      intermetatarsal angles. We sought to determine the relationship between the
      radiographic and magnetic resonance imaging (MRI) measurements because this is
      not yet known. Two of us analyzed a series of 56 consecutive patients who had had
      radiographs and MRI performed on the same foot between April 27, 2015 and March
      9, 2016 and who satisfied all other inclusion and exclusion criteria (age 18 to
      100 years, no history of recent foot trauma, and no metal hardware in the foot).
      We found excellent interreader reliability (intraclass correlation 0.89 to 0.96)
      and intermodality agreement (intraclass correlation 0.83 to 0.91). The HV angle
      measured 15.0 degrees  +/- 8.8 degrees  on the MRI scans and 13.8 degrees  +/-
      8.7 degrees  on the radiographs (mean difference -1.15 degrees  +/- 3.89 degrees
      ), and the intermetatarsal angle was 9.0 degrees  +/- 3.1 degrees  on the MRI
      scans and 8.8 degrees  +/- 2.9 degrees  on the radiographs (mean difference -0.22
      degrees  +/- 2.10 degrees ). The HV measurements were reliable on both
      radiographs and MRI for the range of values tested. Small intermodality
      statistically significant differences in HV angle measurements were found;
      however, these might not be enough to be clinically significant.

PMID- 29331289
TI  - Titanium Scaffolding: An Innovative Modality for Salvage of Failed First Ray
      Procedures.
AB  - Shortening of the first ray is a potential complication associated with first
      metatarsal procedures. Correction of this deformity conventionally has required
      the use of a tricortical bone graft to lengthen the bone. Graft complications,
      including donor site morbidity, poor graft stability, and graft resorption, have
      revealed a need for an alternative procedure. The present report shows that
      titanium cage scaffolding has lower extremity applications beyond its previous
      uses in the ankle and spine. Two patients underwent surgical correction for
      failed first ray procedures using a titanium cage apparatus with a calcaneal
      autograft and other biologic agents. The scaffolds were appropriately sized to
      fill the defect. Patients remained non-weightbearing until radiographic evidence
      of healing appeared. Success was determined by diminished pain, a return to
      activity, ambulation, and patient satisfaction. Patients exhibited faster-than
      anticipated healing, including a return to protected weightbearing activities and
      increased stability within 6 weeks. Titanium cage implants provide long-term
      stability and resistance to stress and strain in the forefoot. The implant we
      have described, newly applied to the first ray, is analogous to a system used in
      salvage of failed ankle replacements. In addition to reducing reliance on the
      iliac crest bone graft, the titanium cage apparatus is advantageous because it is
      customized to fill a defect using computed tomography scanning, thereby reducing
      graft failure secondary to an improper shape. These cases demonstrate the
      potential beneficial applications for titanium cages in failed first ray
      reconstruction.

PMID- 29331290
TI  - The Use of Ultrasonography to Identify the Intersection of the Dorsomedial
      Cutaneous Nerve of the Hallux and the Extensor Hallucis Longus Tendon: A
      Cadaveric Study.
AB  - Terminal branches of the superficial fibular nerve are at risk of iatrogenic
      damage during foot surgery, including hallux valgus rigidus correction,
      bunionectomy, cheilectomy, and extensor hallucis longus tendon transfer. One
      terminal branch, the dorsomedial cutaneous nerve of the hallux, is particularly
      at risk of injury at its intersection with the extensor hallucis longus tendon.
      Iatrogenic injuries of the dorsomedial cutaneous nerve of the hallux can result
      in sensory loss, neuroma formation, and/or debilitating causalgia. Therefore,
      preoperative identification of the nerve is of great clinical importance. The
      present study used ultrasonography to identify the intersection between the
      dorsomedial cutaneous nerve of the hallux and the extensor hallucis longus tendon
      in cadavers. On ultrasound identification of the intersection, dissection was
      performed to assess the accuracy of the ultrasound screening. The method
      successfully pinpointed the nerve in 21 of 28 feet (75%). The sensitivity,
      positive likelihood ratio, and positive and negative predictive values of
      ultrasound identification of the junction of the dorsomedial cutaneous nerve and
      the extensor hallucis longus tendon were 75%, 75%, 100%, and 0%, respectively. We
      have described an ultrasound protocol that allows for the preoperative
      identification of the dorsomedial cutaneous nerve of the hallux as it crosses the
      extensor hallucis longus tendon. The technique could potentially be used to
      prevent the debilitating iatrogenic injuries known to occur in association with
      many common foot surgeries.

PMID- 29331292
TI  - [Ocular melanocytosis].

PMID- 29331291
TI  - Global MicroRNA Profiling in Human Bone Marrow Skeletal-Stromal or Mesenchymal
      Stem Cells Identified Candidates for Bone Regeneration.
AB  - Bone remodeling and regeneration are highly regulated multistep processes
      involving posttranscriptional regulation by microRNAs (miRNAs). Here, we
      performed a global profiling of differentially expressed miRNAs in bone-marrow
      derived skeletal cells (BMSCs; also known as stromal or mesenchymal stem cells)
      during in vitro osteoblast differentiation. We functionally validated the
      regulatory effects of several miRNAs on osteoblast differentiation and identified
      15 miRNAs, most significantly miR-222 and miR-423, as regulators of
      osteoblastogenesis. In addition, we tested the possible targeting of miRNAs for
      enhancing bone tissue regeneration. Scaffolds functionalized with miRNA nano
      carriers enhanced osteoblastogenesis in 3D culture and retained this ability at
      least 2 weeks after storage. Additionally, anti-miR-222 enhanced in vivo ectopic
      bone formation through targeting the cell-cycle inhibitor CDKN1B (cyclin
      dependent kinase inhibitor 1B). A number of additional miRNAs exerted additive
      osteoinductive effects on BMSC differentiation, suggesting that pools of miRNAs
      delivered locally from an implanted scaffold can provide a promising approach for
      enhanced bone regeneration.

PMID- 29331294
TI  - [Study of the results scleral-fixated intraocular lenses in the absence of
      capsular support].
AB  - INTRODUCTION: In the absence of sufficient capsular support, scleral fixation of
      the intraocular lens is an interesting alternative. The goal is to evaluate this
      implantation technique when traditional implantation is impossible. PATIENTS AND
      METHODS: This is an observational, retrospective, monocentric study at the Amiens
      university medical center between August 2013 and March 2016. Patients all
      underwent scleral fixation of a three-piece implant without suturing of the
      haptics, after posterior vitrectomy. All patients requiring implantation in the
      absence of stable capsular support were included. Patients with adequate iris or
      capsular support were excluded from our study. RESULTS: Eighteen patients were
      included, with an average age of 69.3+/-16.9 years. The surgical indications
      were: complicated surgery, trauma and endothelial decompensation. The
      preoperative mean corrected visual acuity was 1.2+/-0.4 LogMAR while the
      postoperative acuity was 0.7+/-0.5 LogMAR. The mean postoperative corneal
      astigmatism was 1.9+/-1.9 diopters. The main complications observed were ocular
      hypertension, macular edema, retinal detachment, iris incarceration and
      exteriorization of the haptic. DISCUSSION: There are two alternatives when faced
      with lack of a sufficient capsular support: scleral fixation or iris fixation.
      Our technique is the only one achievable in the presence of iris atrophy.
      Furthermore, it induces less astigmatism and enables the repositioning of a three
      piece implant dislocated into the vitreous. CONCLUSION: Scleral fixation is a
      technique allowing both a satisfactory and a lasting functional result and is to
      be considered when faced with a lack of sufficient capsular support.

PMID- 29331293
TI  - Toric lens implantation in cataract surgery: Automated versus manual horizontal
      axis marking, analysis of 50 cases.
AB  - SUBJECT: The main objective of our study was to evaluate the contribution of
      automated conjunctival registration in the alignment of toric intraocular lenses
      by comparing automated registration optimized with Callisto(r) to manual marking
      of the horizontal axis. MATERIALS AND METHODS: We performed a prospective,
      descriptive, monocentric study on patients undergoing cataract surgery with a
      toric intraocular lens (Asphina 709 Zeiss), performed by a surgeon with good
      experience in toric implants, between September 2016 and March 2017. We analyzed
      the agreement between the manual marking of the 0-180 degrees  axis versus the
      one automatically generated by the CallistoTM, as well as the alignment of the
      IOL and the refractive results at 1 month. RESULTS: We included 50 eyes of 38
      patients. The mean corrected astigmatism was 1,9 D. The mean difference between
      the 2 axes was 4,7 degrees  [0-12.3 degrees ]. Only 50 % of the preoperative
      manual markings were consistent with the automated measurement (<5 degrees ). At
      one month, the mean rotation recorded was 4,3 degrees  [0-29 degrees ]. The
      alignment was identical for 70 % (n=35) of the IOLs (<=5 degrees ). As for
      residual subjective astigmatism, the mean was 0.58 D. The mean visual acuity
      without correction was 8/10 and 55 % saw 10/10 without correction. DISCUSSION:
      Refractive performance depends on preoperative measurement, correct alignment of
      the IOL and its stability in the bag. Our study shows the value of automated
      conjunctival registration in the determination of the intraoperative axis of
      alignment, even with an experienced surgeon. This precision is essential for a
      good refractive result, especially since residual astigmatism in the case of
      misalignment will increase with the power of the implant. CONCLUSION: Our study
      shows excellent refractive results, regardless of the initial astigmatism, using
      automated alignment. Precision of toric implantation opens the way to toric
      multifocal implantation under the best conditions.

PMID- 29331295
TI  - Helicopter Mountain Rescue in Slovenia from 2011 to 2015.
AB  - INTRODUCTION: The popularity of adventure recreation in wilderness areas across
      the world continues to increase. Nevertheless, the risk of injury and illness
      remains significant. The purpose of this study is to analyze the mountain rescue
      operations performed in Slovenia between 2011 and 2015. METHODS: This
      retrospective study reports mountain rescue operations documented by the
      Slovenian National Mountain Rescue Association. The annual number of ground-based
      and helicopter-based rescues were identified and compared. For 2015, the
      indication for rescue and the severity of injury were also analyzed, specifically
      for interventions requiring the use of a helicopter. RESULTS: From 2011 through
      2015, the number of rescues remained consistent with an annual average of 413 (SD
      +/-15; range, 393-434) rescues. However, the percentage of ground-based rescues
      varied significantly year by year (P=0.016), with highest rate in 2014 (68%) and
      the lowest in 2015 (56%). In 2015, 434 mountain rescue operations were reported
      in Slovenia. Injury accounted for 44%, illness for 10%, and fatality for 9% of
      the rescues. In 37%, no illness or injury was reported. Helicopter rescue was
      used in 190 (44%) of all interventions. Among the 190 helicopter rescues, 49% of
      patients had nonfatal injuries, 29% required no medical treatment, 15% had
      illness, and 7% had fatal injuries. CONCLUSIONS: A significant number of mountain
      rescue operations were conducted in Slovenia from 2011 through 2015. Most of
      these were needed for injured, ill, or deceased persons. A notable number of
      rescues in 2015 required a helicopter.

PMID- 29331296
TI  - A Case of Autosplenectomy in Sickle Cell Trait Following an Exposure to High
      Altitude.
AB  - A 24-year-old man presented with acute abdominal pain upon ascent to moderate
      altitude (3500 m). An immediate evaluation revealed a splenic infarct, and he was
      evacuated to sea level. Upon recovery, he was sent back to 3500 m without
      detailed etiological evaluation, whereupon he experienced recurrent episodes of
      left-side subcostal pain. Imaging suggested autosplenectomy, and workup revealed
      a negative thrombophilia profile but was positive for sickle cell trait (SCT).
      Individuals with SCT can be asymptomatic until exposure to severe hypoxia, upon
      which they can manifest clinically as sickle cell syndrome. We discuss the rare
      presentation of autosplenectomy in a patient with previously undiagnosed SCT on
      exposure to high altitude.

PMID- 29331297
TI  - Elevation 3 mm: A Case of a Cardiac Emergency and Rescue on Mount Monadnock.

PMID- 29331298
TI  - Spatiotemporal characterization of microdamage accumulation in rat ulnae in
      response to uniaxial compressive fatigue loading.
AB  - Repetitive fatigue loading can induce microdamage accumulation in bone matrix,
      which results in impaired mechanical properties and increased fracture
      susceptibility. However, the spatial distribution and time-variant process of
      microdamage accumulation in fatigue-loaded skeleton, especially for linear
      microcracks which are known to initiate bone remodeling, remain not fully
      understood. In this study, the time-varying process of the morphology and
      distribution of microcracks in rat ulnae subjected to uniaxial compressive
      fatigue loading was investigated. Right forelimbs of thirty four-month-old male
      Sprague-Dawley rats were subjected to one bout of cyclic ramp loading with 0.67
      Hz at a normalized peak force of 0.055 N/g body weight for 6000 cycles, and the
      contralateral left ulnae were not loaded as the control samples. Ten rats were
      randomly euthanized on Days 3, 5, and 7 post fatigue loading. Our findings via
      two-dimensional histomorphometric measurements based on basic fuchsin staining
      and three-dimensional quantifications using contrast-enhanced micro-computed
      tomography (MicroCT) with precipitated BaSO4 staining demonstrated that the
      accumulation of linear microcracks (increase in the amount of linear microcracks)
      on Day 5 was significantly higher than that on Day 3 and Day 7 post fatigue
      loading. Our histological and histomorphometric results revealed that linear
      microcrack density (Cr.Dn) in the tensile cortex at Days 3, 5 and 7 post fatigue
      loading was significantly higher than that in the compressive side, whereas
      linear microcrack length (Cr.Le) in the tensile cortex at Day 3 was significantly
      lower than that in the compressive cortex. Our findings revealed that microcrack
      accumulation exhibited a non-linear time-varying process at 3, 5 and 7 days post
      axial compressive fatigue loading (with observable peak Cr.Dn at Day 5). Our
      findings also revealed distinct distribution of microcrack density and morphology
      in rat ulnae with tensile and compressive strains, as characterized by more
      microcracks accumulated in tensile cortices, and longer cracks shown in
      compressive cortices.

PMID- 29331299
TI  - The regulatory roles of Notch in osteocyte differentiation via the crosstalk with
      canonical Wnt pathways during the transition of osteoblasts to osteocytes.
AB  - Osteocytes comprise more than 90% of the cells in bone and are differentiated
      from osteoblasts via an unknown mechanism. Recently, it was shown that Notch
      signaling plays an important role in osteocyte functions. To gain insights into
      the mechanisms underlying the functions of Notch in regulating the transition of
      osteoblasts to osteocytes, we performed a luciferase assay by cloning the
      proximal E11 and dentin matrix acidic phosphoprotein 1 (DMP1) promotor regions
      into pGluc-Basic 2 vectors, which were subsequently transfected into the IDG-SW3
      (osteocytes), MC3T3 (osteoblasts) and 293T (non-osteoblastic cells) cell lines.
      Two approaches were used to activate Notch signaling in vitro. One was a Notch1
      extracellular antibody-coated cell culture plate, and the other was transfection
      of a Hairy/Enhancer of Split 1 (Hes1) overexpression vector. The interaction
      between the Notch and Wnt signaling pathways was probed by assessing the
      expression of a series of phosphorylated proteins involved in the cascade of both
      signaling pathways. Our data suggested that Notch signaling regulates E11
      expression through Hes1 activity, while Hes1 solely did not initiate the
      expression of DMP1. The regulatory function of E11 by Hes1 was not observed in
      the 293T cell line, indicating a cell context-dependent manner of the Notch
      signaling pathway. Additionally, we found that Notch inhibited Wnt signaling at
      the late differentiation stage of osteocytes by both directly repressing
      phosphorylated Akt and preventing the nuclear aggregation of beta-catenin. These
      findings provide profound understandings of Notch's regulatory function in
      osteocyte differentiation.

PMID- 29331300
TI  - Cigarette smoking and hip volumetric bone mineral density and cortical volume
      loss in older adults: The AGES-Reykjavik study.
AB  - This study aimed to explore the relationships of several indicators of cigarette
      smoking habits (smoking status, pack-years, age at smoking initiation and smoking
      cessation) with quantitative computed tomographic (QCT)-derived proximal femur
      bone measures (trabecular vBMD, integral vBMD and the ratio of cortical to total
      tissue volume (cvol/ivol)) and with subsequent change in these measures over the
      next five years. A total of 2673 older adults (55.9% women), aged 66-92 years at
      baseline from the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study,
      who had two QCT scans of the hip were studied. In multivariable linear regression
      models, compared to never-smokers, current smokers had lower cvol/ivol at
      baseline and former-smokers had poorer measures on all outcomes (lower trabecular
      vBMD, integral vBMD and cvol/ivol), even when adjusted for several potential
      confounders. Further, among former smokers, those with higher pack-years had
      worse bone outcomes and those with longer duration since smoking cessation had
      better bone health at baseline. Analyses of change in bone measures revealed that
      compared to never-smokers, current smokers had significantly greater loss of
      trabecular vBMD, integral vBMD, and cvol/ivol. The regression models included
      adjustment for sex, age, education, and baseline body mass index, creatinine, %
      weight change from age 50, 25OHD, physical activity level, high-sensitive C
      Reactive protein levels, alcohol and coffee consumption, history of diabetes
      mellitus, arthritis, and respiratory diseases. In conclusion, both current and
      former smoking showed adverse associations with bone health assessed with QCT.
      Results suggest that current smoking in particular may aggravate the rate of bone
      loss at older age and highlight implications for targeting this risk factor in
      populations that present higher smoking prevalence and vulnerability to bone
      fragility.

PMID- 29331302
TI  - Bone matrix microdamage and vascular changes characterize bone marrow lesions in
      the subchondral bone of knee osteoarthritis.
AB  - INTRODUCTION: Bone marrow lesions (BMLs) in the subchondral bone in
      osteoarthritis (OA) are suggested to be multifactorial, although the pathogenic
      mechanisms are unknown. Bone metabolism and cardiovascular risk factors associate
      with BML in epidemiologic studies. However, there are no studies at the tissue
      level investigating the relationship between these processes and BML. The aim of
      this study was to investigate the relationship between BMLs in the tibial plateau
      (TP) of knee OA and bone matrix microdamage, osteocyte density and vascular
      changes. METHODS: TP were obtained from 73 patients at total knee replacement
      surgery and BMLs were identified ex vivo in TP tissue using MRI. Comparator 'No
      BML' tissue was from matched anatomical sites to the BMLs. Quantitative
      assessment was made of subchondral bone microdamage, bone resorption indices,
      osteocyte cellularity, and vascular features. RESULTS: Several key parameters
      were different between BML and No BML tissue. These included increased microcrack
      burden (p = .01, p = .0001), which associated positively with bone resorption and
      negatively with cartilage volume, and greater osteocyte numerical density (p =
      .02, p = .01), in the subchondral bone plate and subchondral trabeculae,
      respectively. The marrow tissue within BML zones contained increased arteriolar
      density (p = .04, p = .0006), and altered vascular characteristics, in particular
      increased wall thickness (p = .007) and wall:lumen ratio (wall thickness over
      internal lumen area) (p = .001), compared with No BML bone. CONCLUSIONS:
      Increased bone matrix microdamage and altered vasculature in the subchondral bone
      of BMLs is consistent with overloading and vascular contributions to the
      formation of these lesions. Given the important role of BMLs in knee OA, these
      contributing factors offer potential targets for the treatment and prevention of
      knee OA.

PMID- 29331303
TI  - Clear, professional and accurate communication is key to success in all
      activities.

PMID- 29331301
TI  - Marrow adipose tissue imaging in humans.
AB  - Bone strength is affected not only by bone mineral density (BMD) and bone
      microarchitecture but also its microenvironment. Recent studies have focused on
      the role of marrow adipose tissue (MAT) in the pathogenesis of bone loss.
      Osteoblasts and adipocytes arise from a common mesenchymal stem cell within bone
      marrow and many osteoporotic states, including aging, medication use, immobility,
      over - and undernutrition are associated with increased marrow adiposity.
      Advancements in imaging technology allow the non-invasive quantification of MAT.
      This article will review magnetic resonance imaging (MRI)- and computed
      tomography (CT)-based imaging technologies to assess the amount and composition
      of MAT. The techniques that will be discussed are anatomic T1-weighted MRI, water
      fat imaging, proton MR spectroscopy, single energy CT and dual energy CT.
      Clinical applications of MRI and CT techniques to determine the role of MAT in
      patients with obesity, anorexia nervosa, and type 2 diabetes will be reviewed.

PMID- 29331304
TI  - Gender Representation in Urologic Subspecialties.
AB  - OBJECTIVE: To examine associations between urologic subspecialization, surgeon
      gender and practice patterns among certifying urologists over the last 13 years.
      MATERIALS AND METHODS: Demographic data of certifying and recertifying urologists
      (2004 to 2015) were obtained from the American Board of Urology. We investigated
      gender-specific trends in self-reported practice type (academic practice, private
      practice), subspecialization, and employment as a full-time vs part-time
      physician, relative to certification year and cycle. RESULTS: Of 9140 urologists
      applying for certification or recertification over the study period, 815 (8.9%)
      were women. The largest proportion of female surgeon candidates (65.0%) was first
      time certifiers. Women represented 16.7% of first-time certifying urologists (P <
      .001) and reported practicing in academia more frequently (23.6%) compared with
      13.7% of men (P < .001). Female surgeons identified as subspecialists in greater
      numbers (46.4%) than their male counterparts (23.4%) across all certification
      years and cycle cohorts (P < .001). Women reported subspecializing in female
      urology (24.2%) and pediatrics (10.2%) at higher frequencies than their male
      colleagues (4.6% and 3.1% respectively, both P < .001). Female and male surgeon
      candidates requested certification in equal proportion in andrology and
      infertility (P = .83) and endourology (3.6% female vs 5.8% male, P = .13),
      however differed in oncology (4.2% female vs 7.2% male, P = .001). CONCLUSION: A
      growing proportion of certifying urologists are women, with the greatest
      enrichment among those seeking first-time certification. Since 2004, female
      surgeons account for a disproportionate volume of urologists who practice in the
      academic setting and identify as subspecialists.

PMID- 29331305
TI  - TIGAR inhibits ischemia/reperfusion-induced inflammatory response of astrocytes.
AB  - The inflammatory response of glial cells contributes to neuronal damage or repair
      after brain ischemia/reperfusion insult. We previously demonstrated a protective
      role of TP53-induced glycolysis and apoptosis regulator (TIGAR) in ischemic
      neuronal injury through increasing the flow of pentose phosphate pathway (PPP).
      The present study investigated the possible role of TIGAR in ischemia/reperfusion
      induced inflammatory response of astrocytes. Male ICR mice were subjected to
      middle cerebral artery occlusion for 2 h followed by 24 h reperfusion and
      cultured primary astrocytes were subjected to oxygen glucose deprivation for 9 h
      followed by 24 h reoxygenation (OGD/R). Adenoviral vectors were used to alter the
      levels of TIGAR protein in brain and in culture primary astrocytes. We showed
      that during the OGD/R insult the protein levels of TIGAR were rapidly increased
      in astrocytes. Overexpression of TIGAR mediated increased the viability, levels
      of NADPH and rGSH, and reduced intracellular reactive oxygen species (ROS) in
      cultured primary astrocytes. Overexpression of TIGAR not only significantly
      reduced infarct volume after stroke insult but also markedly reduced long-term
      mortality and improved recovery of neurological functions. Overexpression of
      TIGAR tempered OGD/R- or ischemia/reperfusion-induced the upregulation of
      inducible nitric oxide synthase (iNOS), cyclooxygenases COX2 and the release of
      pro-inflammatory cytokines interleukin 1 beta (IL-1beta) and tumor necrosis
      factor-alpha (TNF-alpha), while TIGAR knockdown produced opposite effects on
      these parameters. Moreover, Overexpression of TIGAR suppressed OGD/R-induced
      degradation of IkappaBalpha and NF-kappaB nuclear translocation in cultured
      primary astrocytes. The present study elucidates a novel mechanism by which TIGAR
      protects neurons against ischemia/reperfusion injury.

PMID- 29331306
TI  - Primary mucinous eccrine carcinoma of the buccal space: A case report and review
      of the literature.
AB  - IMPORTANCE: Mucinous eccrine carcinoma is a rare entity that most commonly
      affects the head and neck. Due to its low frequency of occurrence, review of its
      etiology, histopathology, and treatment strategies is beneficial to all
      clinicians who may encounter similar appearing masses. OBSERVATION: An 84-year
      old male presented with a blue mass on the left cheek. This mass started as a
      small bump and grew significantly over one year. His primary care physician
      monitored its growth and ultimately referred to an otolaryngologist. Imaging
      findings revealed a multi-lobular solid and cystic left buccal lesion. FNA was
      suggestive of low grade mucoepidermoid carcinoma. INTERVENTION: Patient underwent
      surgical excision with primary closure of the defect. Frozen section was
      consistent with low grade salivary malignancy. Final pathology revealed primary
      mucinous eccrine carcinoma of the skin. CONCLUSIONS AND RELEVANCE: Mucinous
      eccrine carcinoma is a rare entity commonly seen in the head and neck region.
      Mucinous deposits to the skin from primaries elsewhere in the body are much more
      common than primary lesions of the skin. Histology is a key component of the
      diagnosis but full oncologic workup is required. Treatment typically includes
      wide local excision with possible adjuvant chemotherapy or radiation for high
      risk features.

PMID- 29331308
TI  - A tribute in life to the world icon of the cardiology of heights: Dr. Dante
      Penaloza from Peru.

PMID- 29331307
TI  - Risk factors of sensorineural hearing loss in patients with unilateral safe
      chronic suppurative otitis media.
AB  - PURPOSE: Chronic suppurative otitis media (CSOM) is the major cause of hearing
      impairment, especially conductive hearing loss. Few patients also had
      sensorineural component, the sensorineural hearing loss (SNHL) in CSOM is
      controversial, especially for safe mucosal type. This study aims to assess the
      relationship between the frequency of SNHL development in patients with safe
      mucosal CSOM and its relation to patient's age, sex, duration of disease, size of
      perforation and different audiological findings. MATERIAL AND METHODS: This is a
      prospective study conducted from June 2016 to June 2017 in a tertiary referral
      hospital. 200 patients with unilateral mucosal type of CSOM with normal
      contralateral ear were included in the study. The diseased ears were taken as
      study ears and normal ears as control ears in all patients. Detailed otologic
      history, clinical and audiometric findings were recorded and analyzed. Results
      were statistically compared in all patients for both study and control ears using
      different parameters. RESULTS: Twenty patients had an average bone conduction
      threshold of all frequencies above 25dB, which implies SNHL (10%). The incidence
      of SNHL was statistically significant at higher speech frequencies. The incidence
      increased with the presence of Diabetes Mellitus, smoking, duration of disease,
      presence of active discharge and the increase in size of perforation. However, it
      is not age dependent and there was no difference between males and females.
      CONCLUSION: Safe mucosal CSOM can cause SNHL with multiple predisposing factors.

PMID- 29331309
TI  - What is the predictive value of ST segment depression in inferior leads in first
      acute anterior myocardial infarction?
AB  - BACKGROUND: Electrical phenomenon and remote myocardial ischemia are the main
      factors of ST segment depression in inferior leads in acute anterior myocardial
      infarction (AAMI). We investigated the prognostic value of the sum of ST segment
      depression amplitudes in inferior leads in patients with first AAMI treated with
      primary percutaneous coronary intervention. (PPCI). METHODS: In this prospective
      analysis, we evaluated the in-hospital prognostic impact of the sum of ST segment
      depression in inferior leads on 206 patients with first AAMI. Patients were
      stratified by tertiles of the sum of admission ST segment depression in inferior
      leads. Clinical outcomes were compared between those tertiles. RESULTS:
      Univariate analysis revealed higher rate of in-hospital death for patients with
      ST segment depression in inferior leads in tertile 3, as compared to patients in
      tertile 1 (OR 9.8, 95% CI 1.5-78.2, p<0.001). After adjustment for baseline
      variables, ST segment depression in inferior leads in tertile 3 was associated
      with 5.7-fold hazard of in-hospital death (OR: 5.7, 95% CI 1.2-35.1, p<0.001).
      Spearman rank correlation test revealed correlation between the sum of ST segment
      depression amplitude in inferior leads and the sum of ST segment elevation
      amplitude in V1-6, L1 and aVL. Multivessel disease and additional RCA stenosis
      were also detected more often in tertile 3. CONCLUSION: The sum of ST segment
      depression amplitude in inferior leads of admission ECG in patients with first
      AAMI treated with PPCI provide an independent prognostic marker of in-hospital
      outcomes. Our data suggest the sum of ST segment depression amplitude to be a
      simple, feasible and clinically applicable tool for rapid risk stratification in
      patients with first AAMI.

PMID- 29331310
TI  - Blood eosinophil counts as a guide for COPD treatment strategies.

PMID- 29331311
TI  - Prediction of mortality in patients with chronic obstructive pulmonary disease
      with the new Global Initiative for Chronic Obstructive Lung Disease 2017
      classification: a cohort study.
AB  - BACKGROUND: The Global Initiative for Chronic Obstructive Lung Disease (GOLD)
      2017 classification separates the spirometric 1-4 staging from the ABCD groups
      defined by symptoms and exacerbations. Little is known about how this new
      classification predicts mortality in patients with chronic obstructive pulmonary
      disease (COPD). We aimed to establish the predictive ability of the GOLD 2017
      classification, compared with earlier classifications, for all-cause and
      respiratory mortality, both when using its main ABCD groups and when further
      subdividing according to spirometric 1-4 staging. METHODS: In this nationwide
      cohort study, we enrolled patients with COPD with data available in the Danish
      registry for COPD. To be included in this registry, individuals must have been
      outpatients in hospital-based pulmonary clinics in Denmark. Eligible patients
      were aged 30 years or older; had received a primary diagnosis of COPD
      (International Classification of Diseases [ICD]-10 J44.X) or acute respiratory
      failure (ICD-10 J96.X) in combination with COPD (ICD-10 J44.X) as a secondary
      diagnosis; and had complete data on FEV1, body-mass index, modified Medical
      Research Council dyspnoea scale score, and smoking status. We categorised
      eligible patients with complete data according to the 2007, 2011, and 2017 GOLD
      classifications at the first contact with an outpatient clinic. For the GOLD 2017
      classification, we further subdivided the patients by spirometry into 16
      subgroups (1A to 4D). We calculated adjusted hazard ratios (HRs) for all-cause
      and respiratory mortality and compared the predictive ability of the three GOLD
      classifications (2007, 2011, and 2017) using receiver operating curves. FINDINGS:
      We enrolled 33 765 patients with COPD, who were outpatients in Danish hospitals
      between Jan 1, 2008, and Nov 30, 2013, in the main cohort assessed for all-cause
      mortality. 22 621 of these patients had data available on cause-specific
      mortality (respiratory) and were included in a subcohort followed from Jan 1,
      2008, to Dec 31, 2011. For the GOLD 2017 classification, 3 year mortality
      increased with increasing exacerbations and dyspnoea from group A (all-cause
      mortality 10.0%, respiratory mortality 3.0%) to group D (all-cause mortality
      36.9%, respiratory mortality 18.0%). However, 3 year mortality was higher for
      group B patients (all-cause mortality 23.8%, respiratory mortality 9.7%) than for
      group C patients (all-cause mortality 17.4%, respiratory mortality 6.4%).
      Compared with group A, adjusted HRs for all-cause mortality ranged from 2.05 (95%
      CI 1.87-2.26) for group B, to 1.47 (1.31-1.65) for group C, and to 3.01 (2.75
      3.30) for group D. Area under the curve for all-cause mortality was 0.61 (95% CI
      0.60-0.61) for GOLD 2007, 0.61 (0.60-0.62) for GOLD 2011, and 0.63 (0.53-0.73)
      for GOLD 2017. Area under the curve for respiratory mortality was 0.64 (0.62
      0.65) for GOLD 2007, 0.63 (0.62-0.64) for GOLD 2011, and 0.65 (0.53-0.78) for
      GOLD 2017. The GOLD 2017 classification based on ABCD groups only did not predict
      mortality better than the earlier 2007 and 2011 GOLD classifications. However,
      when 16 subgroups (1A to 4D) were defined, the new classification predicted
      mortality more accurately than the previous systems (p<0.0001). INTERPRETATION:
      We showed that the new GOLD 2017 ABCD classification does not predict all-cause
      and respiratory mortality more accurately than the previous GOLD systems from
      2007 and 2011. FUNDING: Danish Lung Association, Program for Clinical Research
      Infrastructure.

PMID- 29331312
TI  - Brighter than GOLD.

PMID- 29331313
TI  - Predictors of exacerbation risk and response to budesonide in patients with
      chronic obstructive pulmonary disease: a post-hoc analysis of three randomised
      trials.
AB  - BACKGROUND: The peripheral blood eosinophil count might help identify those
      patients with chronic obstructive pulmonary disease (COPD) who will experience
      fewer exacerbations when taking inhaled corticosteroids (ICS). Previous post-hoc
      analyses have proposed eosinophil cutoffs that are both arbitrary and limited in
      evaluating complex interactions of treatment response. We modelled eosinophil
      count as a continuous variable to determine the characteristics that determine
      both exacerbation risk and clinical response to ICS in patients with COPD.
      METHODS: We analysed data from three AstraZeneca randomised controlled trials of
      budesonide-formoterol in patients with COPD with a history of exacerbations and
      available blood eosinophil counts. Patients with any history of asthma were
      excluded. Negative binomial regression analysis was done using splines for
      modelling of continuous variables to study the primary outcome of annual
      exacerbation rate adjusted for exposure time and study design. The trials are
      registered with ClinicalTrials.gov, NCT00206167, NCT00206154, and NCT00419744.
      FINDINGS: 4528 patients were studied. A non-linear increase in exacerbations
      occurred with increasing eosinophil count in patients who received formoterol
      alone. At eosinophil counts of 0.10 * 109 cells per L or more, a significant
      treatment effect was recorded for exacerbation reduction with budesonide
      formoterol compared with formoterol alone (rate ratio 0.75, 95% CI 0.57-0.99;
      pinteraction=0.015). Interactions were observed between eosinophil count and the
      treatment effects of budesonide-formoterol over formoterol on St George's
      Respiratory Questionnaire (pinteraction=0.0043) and pre-bronchodilator FEV1
      (linear effect p<0.0001, pinteraction=0.067). Only eosinophil count and smoking
      history were independent predictors of response to budesonide-formoterol in
      reducing exacerbations (eosinophil count, pinteraction=0.013; smoking history,
      pinteraction=0.015). INTERPRETATION: In patients with COPD treated with
      formoterol, blood eosinophil count predicts exacerbation risk and the clinical
      response to ICS. FUNDING: AstraZeneca.

PMID- 29331314
TI  - Chloroquine inhibits autophagy and deteriorates the mitochondrial dysfunction and
      apoptosis in hypoxic rat neurons.
AB  - AIMS: Mitochondrial dysfunction (MD) and apoptosis in the neurons are associated
      with neonatal hypoxic-ischemic (HI) encephalopathy (HIE). The present study was
      to explore the influence of autophagy on the induction of MD and apoptosis in the
      neurons in a neonatal HIE rats and in hypoxia-treated neurons in vitro. MATERIALS
      AND METHODS: Ten-day-old HI rat pups were sacrificed for brain pathological
      examination and immunohistochemical analysis. The induction of autophagy,
      apoptosis and MD were also determined in the neurons under hypoxia, with or
      without autophagy inhibitor, chloroquine (CQ) treatment. KEY FINDINGS: HI
      treatment caused atrophy and apoptosis of neurons, with a significantly increased
      levels of apoptosis- and autophagy-associated proteins, such as cleaved caspase 3
      and the B subunit of autophagy-related microtubule-associated protein 1 light
      chain 3 (LC3-B). in vitro experiments demonstrated that the hypoxia induced
      autophagy in neurons, as was inhibited by CQ. The hypoxia-induced cytochrome c
      release, cleaved caspase 3 and cleaved caspase 9 were aggravated by CQ. Moreover,
      there were higher levels of reactive oxygen species, more mitochondrial
      superoxide and less mitochondrial membrane potential in the CQ-treated neurons
      under hypoxia than in the neurons singularly under hypoxia. SIGNIFICANCE:
      Apoptosis and autophagy were induced in HI neonatal rat neurons, autophagy
      inhibition deteriorates the hypoxia-induced neuron MD and apoptosis. It implies a
      neuroprotection of autophagy in the hypoxic-ischemic encephalopathy.
      Administration of autophagy inducer agents might be promising in HIE treatment.

PMID- 29331315
TI  - Ethnobotany, phytochemistry and pharmacology of Arctotis arctotoides (L.f.) O.
      Hoffm.: A review.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Arctotis arctotoides (Asteraceae) is part of the
      genus Arctotis. Arctotis is an African genus of approximately 70 species that
      occur widely in the African continent with diverse medicinal values. This plant
      is used for the treatment of indigestion and catarrh of the stomach, epilepsy,
      topical wounds and skin disorders among the ethnic groups in South Africa and
      reported to have a wide spectrum of pharmacological properties. AIM OF THE
      REVIEW: The aim of the present review is to appraise the botany, traditional
      uses, phytochemistry, pharmacological potential, analytical methods and safety
      issues of A. arctotoides. Additionally, this review will help to fill the
      existing gaps in knowledge and highlight further research prospects in the field
      of phytochemistry and pharmacology. MATERIALS AND METHODS: Information on A.
      arctotoides was collected from various resources, including books on African
      medicinal herbs and Zulu medicinal plants, theses, reports and the internet
      databases such as SciFinder, Google Scholar, Pubmed, Scopus, Web of Science, and
      Mendeley by using a combination of various meaningful keywords. This review
      surveys the available literature of the species from 1962 to April 2017. RESULTS:
      In vitro and in vivo studies of the medicinal properties of A. arctotoides were
      reviewed. The main isolated and identified compounds were reported as
      sesquiterpenes, farnesol derivatives, germacranolide, guaianolides and some
      steroids, of which, nine were reported as antimicrobial. Monoterpenoids and
      sesquiterpenoids were the predominant essential oil compound classes of the
      leaves, flowers, stems and roots. The present review revealed potential
      pharmacological properties such as anti-oxidant, antibacterial, antifungal and
      anticancer activities of plant extracts as well as isolated compounds. Moreover,
      the review reports the safety profile (toxicity) of the crude extracts that had
      been screened on brine shrimps, rats and human cell lines. CONCLUSIONS: The
      present review has focused on the phytochemistry, botany, ethnopharmacology,
      biological activities and toxicological information of A. arctotoides. On the
      basis of reported data, A. arctotoides has emerged as a good source of natural
      medicine for the treatment of microbial infections, skin diseases, anti
      inflammatory and anticancer agents and also provides new insights for further
      isolation of new bioactive compounds, especially the discovery of antimicrobial,
      anti-inflammatory and anticancer novel therapeutic lead drug molecules.
      Additionally, intensive investigations regarding pharmacological properties,
      safety assessment and efficacy with their mechanism of action could be future
      research interests before starting clinical trials for medicinal practices.

PMID- 29331317
TI  - Resting-state quantitative EEG characteristics of insomniac patients with
      depression.
AB  - Insomnia is known to show hyperarousal in the central nervous system. However,
      depression that often coexists with insomnia exhibits hypo-activity in the
      frontal lobe, which is very different from insomnia. In the present study, we
      examined wake resting state EEG of insomniac patients with depression to
      investigate whether they could be conceptualized as spectrum of insomnia or
      significantly different from insomnia. We compared the absolute power values of
      EEG spectra of three groups: 15 insomniacs with comorbid depression (CD), age-
      and sex-matched 15 comorbid-free insomniacs (CFI), and 15 good sleep controls
      (GSC). As a result, CD and CFI showed no significant difference in the EEG power
      spectrum analysis. Compared with GSC, however, both CD and CFI groups showed
      increased high frequency EEG amplitude. From these results, we have confirmed
      that CD shows cortical hyperarousal similar to insomnia in the daytime resting
      state. In conclusion, it would be reasonable to understood insomniac patients
      experiencing depression as a continuum of insomnia patients.

PMID- 29331316
TI  - Pharmacological activities of the organic extracts and fatty acid composition of
      the petroleum ether extract from Haplophyllum tuberculatum leaves.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Haplophyllum tuberculatum is used in traditional
      medicine to treat many disorders including inflammation and pain. The aim of this
      study is to investigate the organic extracts from H. tuberculatum leaves against
      inflammation, gastric ulcer and pain. MATERIALS AND METHODS: Acute toxicity was
      studied in vivo to determine the toxic doses of the organic extracts. Anti
      inflammatory activity was also evaluated in vivo using carrageenan-induced paw
      edema in Wistar rats. Gastroprotective activity was tested using the HCl/ethanol
      induced gastric ulcer test in rats. Peripheral and central analgesic activities
      were assessed using the acetic acid-induced writhing test and the hot-plate
      method, respectively. The chemical composition of the fatty acids in the
      petroleum ether (PE) extract was determined with GC-MS. RESULTS: At 25, 50 and
      100mg/kg PE extract was the most active against inflammation. Percentages
      inhibition 5h after carrageenan-injection were 51.12; 86.71% and 96.92%,
      respectively. The same extract at 100mg/kg showed good analgesic activities using
      the acetic acid-induced writhing test and the hot-plate method. The chloroform,
      ethyl acetate (EtOAc) and butanolic (n-BuOH) extracts exhibited strong anti
      inflammatory, gastroprotective and analgesic activities at 100mg/kg. The GC-FID
      analysis revealed that the PE extract was rich in gamma-linolenic acid (45.50%)
      followed by palmitic acid (18.48%), linoleic acid (10.73%), erucic acid (4.72),
      stearic acid (3.96%) and oleic acid (2.57%). CONCLUSION: The results of the
      present study support the traditional use of the leaves of H. tuberculatum and
      may possibly serve as prospective material for further development of safe new
      phytochemical anti-inflammatory, gastroprotective and/or analgesic agents.

PMID- 29331319
TI  - A histopathological and biochemical evaluation of oxidative injury in the sciatic
      nerves of male rats exposed to a continuous 900-megahertz electromagnetic field
      throughout all periods of adolescence.
AB  - The effects on human health of the electromagnetic field (EMF) emitted by mobile
      phones, used by approximately 7 billion people worldwide, have become an
      important subject for scientific research. Studies have suggested that the EMF
      emitted by mobile phones can cause oxidative stress in different tissues and age
      groups. Young people in adolescence, a time period when risky behaviors and
      dependences increase, use mobile phones more than adults. The EMF emitted by
      mobile phones, which are generally carried in the pocket or in bags when not in
      use, will very probably affect the sciatic nerve. No previous study has
      investigated the effect of mobile phone use in adolescence on peripheral nerve.
      This study was planned accordingly. Twenty-four male Sprague Dawley rats aged 21
      days were divided equally into control (CGr), Sham (SGr) and EMF (EMFGr) groups.
      No procedure was performed on CGr rats. EMFGr were exposed to the effect of a 900
      megahertz (MHz) EMF for 1 h at the same time every day between postnatal days 21
      59 (the entire adolescent period) inside a cage in the EMF apparatus. SGr rats
      were placed inside the cage for 1 h every day without being exposed to EMF. All
      rats were sacrificed at the end of the study period, and 1 cm sections of sciatic
      nerve were extracted. Malondialdehyde (MDA), glutathione, catalase (CAT)
      superoxide dismutase (SOD) values were investigated biochemically in half of the
      right sciatic nerve tissues. The other halves of the nerve tissues were subjected
      to routine histopathological tissue procedures, sectioned and stained with
      hematoxylin and eosin (H&E) and Masson's trichrome. Histopathological evaluation
      of slides stained with Masson's trichrome and H&E revealed a normal appearance in
      Schwann cells and axons in all groups. However, there was marked thickening in
      the epineurium of sciatic nerves from EMFGr rats. MDA, SOD and CAT levels were
      higher in EMFGr than in CGr and SGr at biochemical analyses. Apoptotic index (AI)
      analysis revealed a significant increase in the number of TUNEL (+) cells when
      EMFGr was compared with CGr and SGr. In conclusion, our study results suggest
      that continuous exposure to a 900-MHz EMF for 1 h throughout adolescence can
      cause oxidative injury and thickening in the epineurium in the sciatic nerve in
      male rats.

PMID- 29331318
TI  - Developmental changes in the feedback related negativity from 8 to 14 years.
AB  - The study examined age related changes in the magnitude of the Feedback Related
      Negativity (FRN) in 8-14 year old children performing a variation of a Go/No-Go
      task. Participants were presented with four stimuli and tasked with mapping each
      of them either to a response or to a "no response" by trial and error guided by
      feedback. Feedback was valid for two stimuli (Go and No-Go) and invalid (.5
      positive; .5 negative feedback) for the other two stimuli. The amplitude of the
      FRN was evaluated as a function of age separately for Go and No-Go trials. The
      results indicated that while performance on valid Go trials improved with age,
      accuracy on valid No-Go trials remained stable with age. FRN amplitude was found
      to be inversely related to age such that smaller FRN amplitudes were observed in
      older children even after controlling for variance in learning. Additionally, the
      FRN was found as a predictor of post-learning performance on Go trials but not on
      No-Go trials, regardless of age. These results do not provide support to the link
      between the FRN and inhibition control as measured by No-Go performance, but do
      suggest a link with other executive control abilities called for by the Go
      condition.

PMID- 29331321
TI  - This Month in AJP.
AB  - The following highlights summarize research articles that are published in the
      current issue of The American Journal of Pathology.

PMID- 29331320
TI  - Zika, dengue and yellow fever viruses induce differential anti-viral immune
      responses in human monocytic and first trimester trophoblast cells.
AB  - Zika virus (ZIKV) is a mosquito-borne flavivirus associated with severe neonatal
      birth defects, but the causative mechanism is incompletely understood. ZIKV
      shares sequence homology and early clinical manifestations with yellow fever
      virus (YFV) and dengue virus (DENV) and are all transmitted in urban cycles by
      the same species of mosquitoes. However, YFV and DENV have been rarely reported
      to cause congenital diseases. Here, we compared infection with a contemporary
      ZIKV strain (FSS13025) to YFV17D and DENV-4 in human monocytic cells (THP-1) and
      first-trimester trophoblasts (HTR-8). Our results suggest that all three viruses
      have similar tropisms for both cells. Nevertheless, ZIKV induced strong type 1
      IFN and inflammatory cytokine and chemokine production in monocytes and
      peripheral blood mononuclear cells. Furthermore, ZIKV infection in trophoblasts
      induced lower IFN and higher inflammatory immune responses. Placental
      inflammation is known to contribute to the risk of brain damage in preterm
      newborns. Inhibition of toll-like receptor (TLR)3 and TLR8 each abrogated the
      inflammatory cytokine responses in ZIKV-infected trophoblasts. Our findings
      identify a potential link between maternal immune activation and ZIKV-induced
      congenital diseases, and a potential therapeutic strategy that targets TLR
      mediated inflammatory responses in the placenta.

PMID- 29331322
TI  - Expression level of risk genes of MHC class II is a susceptibility factor for
      autoimmunity: New insights.
AB  - To date, the study of the impact of major hystocompatibility complex on
      autoimmunity has been prevalently focused on structural diversity of MHC
      molecules in binding and presentation of (auto)antigens to cognate T cells.
      Recently, a number of experimental evidences suggested new points of view to
      investigate the complex relationships between MHC gene expression and the
      individual predisposition to autoimmune diseases. Irrespective of the nature of
      the antigen, a threshold of MHC-peptide complexes needs to be reached, as well as
      a threshold of T cell receptors engaged is required, for the activation and
      proliferation of autoantigen-reactive T cells. Moreover, it is well known that
      increased expression of MHC class II molecules may alter the T cell receptor
      repertoire during thymic development, and affect the survival and expansion of
      mature T cells. Many evidences confirmed that the level of both transcriptional
      and post-transcriptional regulation are involved in the modulation of the
      expression of MHC class II genes and that both contribute to the predisposition
      to autoimmune diseases. Here, we aim to focus some of these regulative aspects to
      better clarify the role of MHC class II genes in predisposition and development
      of autoimmunity.

PMID- 29331323
TI  - Regulation of inflammatory factors by double-stranded RNA receptors in breast
      cancer cells.
AB  - Malignant cells are not the only components of a tumor mass since other cells
      (e.g., fibroblasts, infiltrating leukocytes and endothelial cells) are also part
      of it. In combination with the extracellular matrix, all these cells constitute
      the tumor microenvironment. In the last decade the role of the tumor
      microenvironment in cancer progression has gained increased attention and
      prompted efforts directed to abrogate its deleterious effects on anti-cancer
      therapies. The immune system can detect and attack tumor cells, and tumor
      infiltrating lymphocytes (particularly CD8 T cells) have been associated with
      improved survival or better response to therapies in colorectal, melanoma,
      breast, prostate and ovarian cancer patients among others. Contrariwise, tumor
      associated myeloid cells (myeloid-derived suppressor cells [MDSCs], dendritic
      cells [DCs], macrophages) or lymphoid cells such as regulatory T cells can
      stimulate tumor growth via inhibition of immune responses against the tumor or by
      participating in tumor neoangiogenesis. Herewith we analyzed the chemokine
      profile of mouse breast tumors regarding their capacity to generate factors
      capable of attracting and sequestering DCs to their midst. Chemoattractants from
      tumors were investigated by molecular biology and immunological techniques and
      tumor infiltrating DCs were investigated for matched chemokine receptors. In
      addition, we investigated the inflammatory response of breast cancer cells, a
      major component of the tumor microenvironment, to double-stranded RNA
      stimulation. By using molecular biology techniques such as qualitative and
      quantitative PCR, PCR arrays, and immunological techniques (ELISA, cytokine
      immunoarrays) we examined the effects of dsRNA treatment on the cytokine
      secretion profiles of mouse and human breast cancer cells and non-transformed
      cells. We were able to determine that tumors generate chemokines that are able to
      interact with receptors present on the surface of tumor infiltrating DCs. We
      observed that PRR signaling is able to modify the production of chemokines by
      breast tumor cells and normal breast cells, thereby constituting a possible
      player in shaping the profile of the leukocyte population in the TME.

PMID- 29331324
TI  - Rectal culture-directed antibiotic prophylaxis before transrectal prostate
      biopsy: Reduced infectious complications and healthcare costs.
AB  - BACKGROUND: Transrectal ultrasound-guided prostate biopsy (TUPB) is associated
      with infectious complications (ICs), which are related to a greater prevalence of
      ciprofloxacin-resistant bacteria (CRB) in rectal flora. We examined the ICs that
      occurred in 2 groups: A guided antibiotic prophylaxis (GP) group and an empiric
      prophylaxis (EP) group. We assessed the financial impact of GP. MATERIAL AND
      METHODS: The GP group was studied prospectively (June 2013 to July 2014). We
      collected rectal cultures (RCs) before the TUPB, which were seeded on selective
      media with ciprofloxacin to determine the presence of CRB. The patients with
      sensitive bacteria were administered ciprofloxacin. Patients with resistant
      bacteria were administered GP according to the RC antibiogram. The EP group was
      studied retrospectively (January 2011 to June 2009). RCs were not performed, and
      all patients were treated with ciprofloxacin as prophylaxis. The ICs in both
      groups were recorded during a period no longer than 30 days following TUPB
      (electronic medical history). RESULTS: Three hundred patients underwent TUPB, 145
      underwent GP, and 155 underwent EP. In the GP group, 23 patients (15.86%)
      presented CRB in the RCs. Only one patient (0.7%) experienced a UTI. In the EP
      group, 26 patients (16.8%) experienced multiple ICs (including 2 cases of sepsis)
      (P<.005). The estimated total cost, including the management of the ICs, was
      ?57,076 with EP versus ?4802.33 with GP. The average cost per patient with EP was
      ?368.23 versus ?33.11 with GP. GP achieved an estimated total savings of
      ?52,273.67. Six patients had to undergo GP to prevent an IC. CONCLUSIONS: GP is
      associated with a marked decrease in the incidence of ICs caused by CRB and
      reduced healthcare costs.

PMID- 29331325
TI  - E-Health Care: Promise or Peril for Chronic Illness.

PMID- 29331326
TI  - Cryptorchidism in Sweden: A Nationwide Study of Prevalence, Operative Management,
      and Complications.
AB  - OBJECTIVES: To review the cumulative prevalence, operative management, and
      complications of treatment for cryptorchidism in Sweden. STUDY DESIGN: A
      nationwide observational study from longitudinal register data of all Swedish
      born boys 0-18 years of age, diagnosed with cryptorchidism from 2001 to 2014.
      Primary outcomes were occurrence and age at primary surgery. Secondary outcomes
      included type of procedure and surgical site infection. RESULTS: Of 20 375 boys
      diagnosed with cryptorchidism in 2001-2014, 12 766 were surgically treated. The
      cumulative childhood prevalence was 1.8% (95% CI, 1.5-2.0), with a higher
      prevalence in boys born prematurely, small for gestational age, or with low birth
      weight. The median age at treatment decreased from 6.2 years in 2001 to 3.4 years
      in 2014 (P < .001). Still, 94.1% (95% CI, 92.7-95.6) had surgery after the
      recommended 1 year of age in 2014. Variations in age at surgery between Swedish
      counties were great (range, 2.9-5.9 years of age). There were no deaths within 30
      days after surgery and the frequency of surgical site infection was low (1.4%;
      95% CI, 1.1-1.6). CONCLUSIONS: The cumulative childhood prevalence of
      cryptorchidism was high, and complications were rare. Few boys underwent surgery
      in a timely manner according to clinical guidelines, and standards of care varied
      considerably across the country. Further research and collective actions are
      needed to improve the detection and management of congenital cryptorchidism.

PMID- 29331328
TI  - Pilot Clinical Trial of High-Flow Oxygen Therapy in Children with Asthma in the
      Emergency Service.
AB  - OBJECTIVES: To assess the efficacy of high-flow nasal cannula (HFNC) oxygen
      therapy and safety in children with asthma and moderate respiratory failure in
      the emergency department (ED). STUDY DESIGN: This was a prospective randomized
      pilot trial of children (aged 1-14 years) presenting to a tertiary academic
      pediatric ED with moderate-to-severe asthma exacerbations between September 2012
      and December 2015. Patients with a pulmonary score (PS) >=6 or oxygen saturation
      <94% with a face mask despite initial treatment (salbutamol/ipratropium bromide
      and corticosteroids) were randomized to HFNC or to conventional oxygen therapy.
      Pharmacologic treatment was at the discretion of attending physicians. The
      primary outcome was a decrease in PS >=2 in the first 2 hours. Secondary outcomes
      included disposition, length of stay, and need for additional therapies. RESULTS:
      We randomly allocated 62 children to receive either HFNC (n = 30) or standard
      oxygen therapy (n = 32). Baseline patient characteristics were similar in the 2
      groups. At 2 hours after the start of therapy, PS had decreased by >=2 points in
      16 patients in the HFNC group (53%) compared with 9 controls (28%) (P = .01).
      Between-group differences in disposition, length of stay, and need for additional
      therapies were not significant. No side effects were reported. CONCLUSION: HFNC
      appears to be superior to conventional oxygen therapy for reducing respiratory
      distress within the first 2 hours of treatment in children with moderate-to
      severe asthma exacerbation refractory to first-line treatment. Further studies
      are needed to demonstrate its overall efficacy in the management of asthma and
      respiratory failure in the ED. TRIAL REGISTRATION: EudraCT: 2012-001771-36.

PMID- 29331327
TI  - A New Approach to Rare Diseases of Children: The Undiagnosed Diseases Network.

PMID- 29331329
TI  - Terra Firma-Forme Dermatosis.

PMID- 29331330
TI  - PC-FACS.
AB  - PC-FACS (Fast Article Critical Summaries for Clinicians in Palliative Care)
      provides hospice and palliative care clinicians with concise summaries of the
      most important findings from more than 100 medical and scientific journals. If
      you have colleagues who would benefit from receivingPC-FACS, please encourage
      them to join the AAHPM at aahpm.org. Comments from readers are welcomed at pc
      facs@aahpm.org.

PMID- 29331332
TI  - HIV infection and its effects on the development of autoimmune disorders.
AB  - More than 35 years have elapsed since the initial outbreak of the HIV/AIDS
      epidemic and the status of a considerable number of patients has changed from a
      fatal disorder to a chronic one where comorbidities including sarcoidosis and
      autoimmune diseases have become relevant and dominant. HIV targets the immune
      system leading to a state of immunodeficiency in a setting of immune activation
      in which CD4+ T cell depletion plays a critical role. The onset, natural history
      and course of HIV-associated autoimmune disease has dramatically changed
      according to the stage of HIV infection and since the introduction of combined
      anti-retroviral therapy. There are some issues that need further study regarding
      therapy, especially when immunosuppressive drugs and biologic agents are under
      consideration. Currently, biologic agents and others immunosuppressive agents are
      recommended when patients have CD4+ T cell counts above 200 cells/mm3 and the HIV
      viral activity is completely suppressed.

PMID- 29331334
TI  - The Future of Our Specialty: Elevating Gynecologic Surgery.

PMID- 29331333
TI  - Influences of conformations of peptides on stereoinversions and/or isomerizations
      of aspartic acid residues.
AB  - Recently, non-enzymatic stereoinversions of aspartic acid (Asp) residues in
      proteins and peptides have been reported. Here, we performed replica exchange
      molecular dynamics (REMD) simulations of model peptides (exon 6, 26A-1, and 26A
      2) extracted from elastin to investigate their structural features, thereby
      revealing the factor that influences stereoinversions. For REMD trajectories, we
      calculated distances between carboxyl carbon in Asp and amide nitrogen in the (n
      + 1) residue (CN distances). Because bond formation between carbon and nitrogen
      is indispensable to the formation of a succinimide intermediate the distance
      between them seems to play an important role in stereoinversion. Moreover, we
      calculated polar surface areas (PSAs) for the trajectories, finding that CN
      distances and PSA were different for each peptide, with the longest CN distance
      and smallest PSA observed for exon 6 peptide, where stereoinversion of Asp is the
      slowest. Although the average CN distance was shorter for exon 26A-1 peptide than
      for exon 26A-2 peptide, the number of conformations with CN distances <3.0 A was
      greater for exon 26A-2 peptide than for exon 26A-1 peptide. Furthermore, PSA for
      amide nitrogen of the (n + 1) residue was larger for exon 26A-2 peptide than for
      exon 26A-1 peptide. These results indicated that the flexibility of Asp and (n +
      1) residues and hydrophilicity of peptides, especially in the (n + 1) residue,
      play important roles in the stereoinversion of Asp. This article is part of a
      Special Issue entitled: D-Amino acids: biology in the mirror, edited by Dr.
      Loredano Pollegioni, Dr. Jean-Pierre Mothet and Dr. Molla Gianluca.

PMID- 29331331
TI  - Interaction of ceramides and tear lipocalin.
AB  - The distribution of lipids in tears is critical to their function. Lipids in
      human tears may retard evaporation by forming a surface barrier at the air
      interface. Lipids complexed with the major lipid binding protein in tears, tear
      lipocalin, reside in the bulk (aqueous) and may have functions unrelated to the
      surface. Many new lipids species have been revealed through recent mass
      spectrometric studies. Their association with lipid binding proteins has not been
      studied. Squalene, (O-acyl) omega-hydroxy fatty acids (OAHFA) and ceramides are
      examples. Even well-known lipids such as wax and cholesteryl esters are only
      presumed to be unbound because extracts of protein fractions of tears were devoid
      of these lipids. Our purpose was to determine by direct binding assays if the
      aforementioned lipids can bind tear lipocalin. Lipids were screened for ability
      to displace DAUDA from tear lipocalin in a fluorescence displacement assay. Di-
      and tri-glycerides, squalene, OAHFA, wax and cholesterol esters did not displace
      DAUDA from tear lipocalin. However, ceramides displaced DAUDA. Apparent
      dissociation constants for ceramide-tear lipocalin complexes using fluorescent
      analogs were measured consistently in the submicromolar range with 3 methods,
      linear spectral summation, high speed centrifugal precipitation and standard
      fluorescence assays. At the relatively small concentrations in tears, all
      ceramides were complexed to tear lipocalin. The lack of binding of di- and tri
      glycerides, squalene, OAHFA, as well as wax and cholesterol esters to tear
      lipocalin is consonant with residence of these lipids near the air interface.

PMID- 29331335
TI  - Corrigendum to "A review of postoperative pain assessment records of nurses?"
      [Applied Nursing Research 38C (2017) 1-4].

PMID- 29331336
TI  - UDP-sugar accumulation drives hyaluronan synthesis in breast cancer.
AB  - Increased uptake of glucose, a general hallmark of malignant tumors, leads to an
      accumulation of intermediate metabolites of glycolysis. We investigated whether
      the high supply of these intermediates promotes their flow into UDP-sugars, and
      consequently into hyaluronan, a tumor-promoting matrix molecule. We quantified
      UDP-N-Acetylglucosamine (UDP-GlcNAc) and UDP-glucuronic acid (UDP-GlcUA) in human
      breast cancer biopsies, the levels of enzymes contributing to their synthesis,
      and their association with the hyaluronan accumulation in the tumor. The content
      of UDP-GlcUA was 4 times, and that of UDP-GlcNAc 12 times higher in the tumors as
      compared to normal glandular tissue obtained from breast reductions. The surge of
      UDP-GlcNAc correlated with an elevated mRNA expression of glutamine-fructose-6
      phosphate aminotransferase 2 (GFAT2), one of the key enzymes in the biosynthesis
      of UDP-GlcNAc, and the expression of GFAT1 was also elevated. The contents of
      both UDP-sugars strongly correlated with tumor hyaluronan levels. Interestingly,
      hyaluronan content did not correlate with the mRNA levels of the hyaluronan
      synthases (HAS1-3), thus emphasizing the role of the UDP-sugar substrates of
      these enzymes. The UDP-sugars showed a trend to higher levels in ductal vs.
      lobular cancer subtypes. The results reveal for the first time a dramatic
      increase of UDP-sugars in breast cancer, and suggest that their high supply
      drives the accumulation of hyaluronan, a known promoter of breast cancer and
      other malignancies. In general, the study shows how the disturbed glucose
      metabolism typical for malignant tumors can influence cancer microenvironment
      through UDP-sugars and hyaluronan.

PMID- 29331339
TI  - Cardiopulmonary hemodynamics and C-reactive protein as prognostic indicators in
      compensated and decompensated cirrhosis.
AB  - BACKGROUND & AIMS: The main stages of cirrhosis (compensated and decompensated)
      have been sub-staged based on clinical, endoscopic, and portal pressure
      (determined by the hepatic venous pressure gradient [HVPG]) features.
      Vasodilation leading to a hyperdynamic circulatory state is central in the
      development of a late decompensated stage, with inflammation currently considered
      a key driver. We aimed to assess hepatic/systemic hemodynamics and inflammation
      (by C-reactive protein [CRP]) among the different sub-stages of cirrhosis and to
      investigate their interrelationship and prognostic relevance. METHODS: A single
      center, prospective cohort of patients with cirrhosis undergoing per protocol
      hepatic and right-heart catheterization and CRP measurement, were classified into
      recently defined prognostic stages (PS) of compensated (PS1: HVPG >=6 mmHg but
      <10 mmHg; PS2: HVPG >=10 mmHg without gastroesophageal varices; PS3: patients
      with gastroesophageal varices) and decompensated (PS4: diuretic-responsive
      ascites; PS5: refractory ascites) disease. Cardiodynamic states based on cardiac
      index (L/min/m2) were created: relatively hypodynamic (<3.2), normodynamic (3.2
      4.2) and hyperdynamic (>4.2). RESULTS: Of 238 patients, 151 were compensated (PS1
      = 25; PS2 = 36; PS3 = 90) and 87 were decompensated (PS4 = 48; PS5 = 39). Mean
      arterial pressure decreased progressively from PS1 to PS5, cardiac index
      increased progressively from PS1-to-PS4 but decreased in PS5. HVPG, model for end
      stage liver disease (MELD), and CRP increased progressively from PS1-to-PS5.
      Among compensated patients, age, HVPG, relatively hypodynamic/hyperdynamic state
      and CRP were predictive of decompensation. Among patients with ascites, MELD,
      relatively hypodynamic/hyperdynamic state, post-capillary pulmonary hypertension,
      and CRP were independent predictors of death/liver transplant. CONCLUSIONS: Our
      study demonstrates that, in addition to known parameters, cardiopulmonary
      hemodynamics and CRP are predictive of relevant outcomes, both in patients with
      compensated and decompensated cirrhosis. LAY SUMMARY: There are two main stages
      in cirrhosis, compensated and decompensated, each with a main relevant outcome.
      In compensated cirrhosis the main relevant outcome is the development of ascites,
      while in decompensated cirrhosis it is death. Major roles of cardiac dysfunction
      and systemic inflammation have been hypothesized in the evolution of the disease
      in decompensated patients. In this study, we have shown that these factors were
      also involved in the progression from compensated to decompensated stage.

PMID- 29331338
TI  - Adiponectin levels in Brazilian adolescents: Distribution and associated factors
      in ERICA survey.
AB  - BACKGROUND: The aim of this study was to evaluate the distribution of adiponectin
      and associated factors with low adiponectin levels in a large sample of
      adolescents from different Brazilian regions. METHODS: This is a national, school
      based, cross-sectional multicenter study of cardiovascular risk factors in
      Brazilian adolescents aged 12 to 17 years. Serum adiponectin levels (MUg/ml) were
      measured by enzyme-linked immunosorbent assay kit. Given the lack of reference
      values, sex-and age-specific median was adopted as the cutoff point, with the
      values below the median representing a higher-risk profile. Associated factors
      with low levels of adiponectin were investigated using Poisson regression.
      RESULTS: The sample consisted of 4546 adolescents, the majority female (61.2%).
      The prevalence of overweight/obesity and abdominal obesity was 30% and 13.4%,
      respectively. The medians of adiponectin were 13.4 MUg/ml (95%CI: 12.8-14.0) in
      males and 14.2 MUg/ml (95%CI: 13.3-15.0) in females. Lower adiponectin levels
      were associated with both overweight (Prevalence Ratios (PR) = 1.17; 95%CI 1.01
      1.36) and obesity (PR = 1.36; 95%CI 1.16-1.56) in males, while, in females,
      adiponectin levels were associated only with obesity (PR = 1.45; 95% CI 1.26
      1.66). Increased waist circumference in both males and females was inversely
      associated with adiponectin level. CONCLUSIONS: Adiponectin levels were lower
      among adolescents with weight excess and abdominal obesity. Male adolescents who
      live in rural areas and study at private schools also showed lower adiponectin
      concentrations.

PMID- 29331340
TI  - Hsp72 protects against liver injury via attenuation of hepatocellular death,
      oxidative stress, and JNK signaling.
AB  - BACKGROUND & AIMS: Heat shock protein (Hsp) 72 is a molecular chaperone that has
      broad cytoprotective functions and is upregulated in response to stress. To
      determine its hepatic functions, we studied its expression in human liver
      disorders and its biological significance in newly generated transgenic animals.
      METHODS: Double transgenic mice overexpressing Hsp72 (gene Hspa1a) under the
      control of a tissue-specific tetracycline-inducible system (Hsp72-LAP mice) were
      produced. Acute liver injury was induced by a single injection of acetaminophen
      (APAP). Feeding with either a methionine choline-deficient (MCD; 8 weeks) or a
      3,5-diethoxycarbonyl-1,4-dihydrocollidine-supplemented diet (DDC; 12 weeks) was
      used to induce lipotoxic injury and Mallory-Denk body (MDB) formation,
      respectively. Primary hepatocytes were treated with palmitic acid. RESULTS:
      Patients with non-alcoholic steatohepatitis and chronic hepatitis C infection
      displayed elevated HSP72 levels. These levels increased with the extent of
      hepatic inflammation and HSP72 expression was induced after treatment with either
      interleukin (IL)-1beta or IL-6. Hsp72-LAP mice exhibited robust, hepatocyte
      specific Hsp72 overexpression. Primary hepatocytes from these animals were more
      resistant to isolation-induced stress and Hsp72-LAP mice displayed lower levels
      of hepatic injury in vivo. Mice overexpressing Hsp72 had fewer APAP protein
      adducts and were protected from oxidative stress and APAP-/MCD-induced cell
      death. Hsp72-LAP mice and/or hepatocytes displayed significantly attenuated Jnk
      activation. Overexpression of Hsp72 did not affect steatosis or the extent of MDB
      formation. CONCLUSIONS: Our results demonstrate that HSP72 induction occurs in
      human liver disease, thus, HSP72 represents an attractive therapeutic target
      owing to its broad hepatoprotective functions. LAY SUMMARY: HSP72 constitutes a
      stress-inducible, protective protein. Our data demonstrate that it is upregulated
      in patients with chronic hepatitis C and non-alcoholic steatohepatitis. Moreover,
      Hsp72-overexpressing mice are protected from various forms of liver stress.

PMID- 29331337
TI  - Elastin in lung development and disease pathogenesis.
AB  - Elastin is expressed in most tissues that require elastic recoil. The protein
      first appeared coincident with the closed circulatory system, and was critical
      for the evolutionary success of the vertebrate lineage. Elastin is expressed by
      multiple cell types in the lung, including mesothelial cells in the pleura,
      smooth muscle cells in airways and blood vessels, endothelial cells, and
      interstitial fibroblasts. This highly crosslinked protein associates with
      fibrillin-containing microfibrils to form the elastic fiber, which is the
      physiological structure that functions in the extracellular matrix. Elastic
      fibers can be woven into many different shapes depending on the mechanical needs
      of the tissue. In large pulmonary vessels, for example, elastin forms continuous
      sheets, or lamellae, that separate smooth muscle layers. Outside of the
      vasculature, elastic fibers form an extensive fiber network that originates in
      the central bronchi and inserts into the distal airspaces and visceral pleura.
      The fibrous cables form a looping system that encircle the alveolar ducts and
      terminal air spaces and ensures that applied force is transmitted equally to all
      parts of the lung. Normal lung function depends on proper secretion and assembly
      of elastin, and either inhibition of elastin fiber assembly or degradation of
      existing elastin results in lung dysfunction and disease.

PMID- 29331341
TI  - Effects of the gut-liver axis on ischaemia-mediated hepatocellular carcinoma
      recurrence in the mouse liver.
AB  - BACKGROUND & AIMS: There is growing evidence that liver graft ischemia
      reperfusion (I/R) is a risk factor for hepatocellular carcinoma (HCC) recurrence,
      but the mechanisms involved are unclear. Herein, we tested the hypothesis that
      mesenteric congestion resulting from portal blood flow interruption induces
      endotoxin-mediated Toll-like receptor 4 (Tlr4) engagement, resulting in elevated
      liver cancer burden. We also assessed the role of remote ischemic preconditioning
      (RIPC) in this context. METHODS: C57Bl/6j mice were exposed to standardized
      models of liver I/R injury and RIPC, induced by occluding the hepatic and femoral
      blood vessels. HCC was induced by injecting RIL-175 cells into the portal vein.
      We further evaluated the impact of the gut-liver axis (lipopolysaccharide (LPS)
      Tlr4 pathway) in this context by studying mice with enhanced (lipopolysaccharide
      infusion) or defective (Tlr4-/- mice, gut sterilization, and Tlr4 antagonist)
      Tlr4 responses. RESULTS: Portal triad clamping provoked upstream mesenteric
      venous engorgement and increased bacterial translocation, resulting in aggravated
      tumor burden. RIPC prevented this mechanism by preserving intestinal integrity
      and reducing bacterial translocation, thereby mitigating HCC recurrence. These
      observations were linked to the LPS-Tlr4 pathway, as supported by the high and
      low tumor burden displayed by mice with enhanced or defective Tlr4 responses,
      respectively. CONCLUSIONS: Modulation of the gut-liver axis and the LPS-Tlr4
      response by RIPC, gut sterilization, and Tlr4 antagonism represents a potential
      therapeutic target to prevent I/R lesions, and to alleviate HCC recurrence after
      liver transplantation and resection. LAY SUMMARY: Cancer recurrence can occur
      after liver resection or liver transplantation for hepatocellular carcinoma
      (HCC). This study suggests that intestinal venous congestion, which often occurs
      during liver surgery, favors the translocation of gut-derived bacterial products
      in the portal vein, thereby facilitating cancer recurrence by enhancing the
      signaling of Toll-like receptor 4 in the liver. Using a mouse model of HCC
      recurrence, we show that strategies that (i) reduce bacterial translocation (by
      gut decontamination, or by protecting the intestine from venous ischemia damage)
      or (ii) inhibit Tlr4 signaling in the liver, could reduce cancer recurrence.

PMID- 29331342
TI  - Development of a prognostic score to predict response to Yttrium-90
      radioembolization for hepatocellular carcinoma with portal vein invasion.
AB  - BACKGROUND & AIMS: Yttrium-90 transarterial radioembolization (TARE) has shown
      promising efficacy in the treatment of patients with hepatocellular carcinoma
      (HCC), associated with portal vein tumor thrombus (PVTT). The aim of this study
      is to identify prognostic factors for survival in patients with HCC and PVTT
      undergoing TARE, and build a prognostic classification for these patients.
      METHODS: This is a single center retrospective study conducted over six years
      (2010-2015), on consecutive patients undergoing TARE. Patients were included if
      they met the following criteria: presence of at least one measurable HCC,
      presence of PVTT not occluding the main portal trunk, absence of extrahepatic
      metastases, Child-Pugh score within B7, Eastern Cooperative Oncology Group
      performance status 0-1. Uni- and multivariable analysis was used to explore the
      variables that showed an independent relationship with survival. A prognostic
      score was then derived, and three prognostic categories were identified. RESULTS:
      A total of 120 patients were included in the study. Median overall survival (OS)
      was 14.1 months (95% CI 10.7-17.5) and median progression-free survival (PFS) was
      6.5 months (95% CI 3.8-9.2). The only variables independently correlated with OS
      were bilirubin, extension of PVTT and tumor burden. Three prognostic categories
      were identified: favourable prognosis (0 points), intermediate prognosis (2-3
      points) and dismal prognosis (>3 points). Median OS in the three categories was
      32.2 months, 14.9 months and 7.8 months respectively (p <0.0001). PFS (p = 0.045)
      and the risk of liver decompensation (p <0.0001) also significantly differed
      along the same prognostic categories. CONCLUSIONS: Radioembolization with Yttrium
      90 is an effective therapy for patients with HCC and PVTT. The proposed
      prognostic stratification may help to better identify good candidates for the
      treatment, and those for whom TARE may be futile. LAY SUMMARY: Yttrium-90
      transarterial radioembolization (TARE) is a microembolic procedure that minimizes
      alterations to hepatic arterial flow, and thus can be safely performed in
      patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus
      (PVTT). In this study, we retrospectively evaluated the independent predictors of
      long-term outcomes in patients with HCC and PVTT treated with TARE. Bilirubin
      level, extension of PVTT and tumor burden were independently related to post
      treatment survival: the combination of these factors allowed us to build a
      prognostic stratification that may help to better identify good candidates for
      the treatment, and those for whom TARE may be futile.

PMID- 29331344
TI  - Feels Not Right Stabbing a Child.

PMID- 29331343
TI  - Irradiation stents vs. conventional metal stents for unresectable malignant
      biliary obstruction: A multicenter trial.
AB  - BACKGROUND & AIMS: Placement of an irradiation stent has been demonstrated to
      offer longer patency and survival than an uncovered self-expandable metallic
      stent (SEMS) in patients with unresectable malignant biliary obstruction (MBO).
      We aim to further assess the efficacy of an irradiation stent compared to an
      uncovered SEMS in those patients. METHODS: We performed a randomized, open-label
      trial of participants with unresectable MBO at 20 centers in China. A total of
      328 participants were allocated in parallel to the irradiation stent group (ISG)
      or the uncovered SEMS group (USG). Endpoints included stent patency (primary),
      technical success, relief of jaundice, overall survival, and complications.
      RESULTS: The first quartile stent patency time (when 25% of the patients
      experienced stent restenosis) was 212 days for the ISG and 104 days for the USG.
      Irradiation stents were significantly associated with a decrease in the rate of
      stent restenosis (9% vs. 15% at 90 days; 16% vs. 27% at 180 days; 21% vs. 33% at
      360 days; p = 0.010). Patients in the ISG obtained longer survival time (median
      202 days vs. 140 days; p = 0.020). No significant results were observed in
      technical success rate (93% vs. 95%; p = 0.499), relief of jaundice (85% vs. 80%;
      p = 0.308), and the incidence of grade 3 and 4 complications (8.5% vs. 7.9%; p =
      0.841). CONCLUSIONS: Insertion of irradiation stents instead of uncovered SEMS
      could improve patency and overall survival in patients with unresectable MBO. LAY
      SUMMARY: For patients with unresectable malignant biliary obstruction (MBO),
      placement of a self-expandable metallic stent (SEMS) is a recommended palliative
      modality to relieve pruritus, cholangitis, pain, and jaundice. However,
      restenosis is a main pitfall after stent placement. Data from this first
      multicenter randomized controlled trial showed that insertion of an irradiation
      stent provided longer patency and better survival than a conventional metal
      stent. ClinicalTrials.gov ID: NCT02001779.

PMID- 29331345
TI  - July 14, 2016, Terror Attack in Nice, France.
AB  - On July 14, 2016, a terrorist attack by truck occurred in Nice, France, during
      the traditional fireworks for Bastille Day. The authors present the point of view
      of the doctors from Lenval University Children's Hospital, which is located near
      the attack place and which had to manage 47 casualties, including 12 adults.

PMID- 29331346
TI  - Predicting Low-Resource-Intensity Emergency Department Visits in Children.
AB  - OBJECTIVES: Interventions to reduce frequent emergency department (ED) use in
      children are often limited by the inability to predict future risk. We sought to
      develop a population-based model for predicting Medicaid-insured children at risk
      for high frequency (HF) of low-resource-intensity (LRI) ED visits. METHODS: We
      conducted a retrospective cohort analysis of Medicaid-insured children (aged 1-18
      years) included in the MarketScan Medicaid database with >=1 ED visit in 2013.
      LRI visits were defined as ED encounters with no laboratory testing, imaging,
      procedures, or hospitalization; and HF as >=3 LRI ED visits within 365 days of
      the initial encounter. A generalized linear regression model was derived and
      validated using a split-sample approach. Validity testing was conducted examining
      model performance using 3 alternative definitions of LRI. RESULTS: Among 743,016
      children with >=1 ED visit in 2013, 5% experienced high-frequency LRI ED use,
      accounting for 21% of all LRI visits. Prior LRI ED use (2 visits: adjusted odds
      ratio = 3.5; 95% confidence interval, 3.3, 3.7; and >=3 visits: adjusted odds
      ratio = 7.7; 95% confidence interval, 7.3, 8.1) and presence of >=3 chronic
      conditions (adjusted odds ratio = 1.7; 95% confidence interval, 1.6, 1.8) were
      strongly associated with future HF-LRI ED use. A model incorporating patient
      characteristics and prior ED use predicted future HF-LRI ED utilization with an
      area under the curve of 0.74. CONCLUSIONS: Demographic characteristics and
      patterns of prior ED use can predict future risk of HF-LRI ED use in the
      following year. Interventions for reducing low-value ED use in these high-risk
      children should be considered.

PMID- 29331347
TI  - Empowering Post-Surgical Patients to Improve Opioid Disposal: A Before and After
      Quality Improvement Study.
AB  - BACKGROUND: Our country is in the midst of an opioid epidemic. Although the
      problem is multifactorial, one issue is the presence of excess prescription
      opioid medications circulating in our communities. Our objective was to determine
      whether dissemination of an educational brochure would improve the disposal of
      unused opioids after surgery. STUDY DESIGN: Eligible surgery patients from an
      upper extremity/peripheral nerve clinic were enrolled into this prospective
      before and after study between February 2017 and September 2017. Patients who
      reported opioid use preoperatively were excluded from this study. The same survey
      was administered to the group of patients who did not receive the intervention
      and to those who did receive the intervention. Our primary endpoint was the
      proportion of patients who disposed of unused opioid medications. RESULTS: A
      total of 334 patients were studied: 164 who did not receive the brochure and 170
      who received the brochure. Seventy-six patients were excluded for preoperative
      opioid use. After dissemination of the brochure, there was a significant increase
      in the proportion of patients who disposed of their unused opioids (11% vs 22%, p
      = 0.02). Of those who disposed of their opioids, there was no significant
      difference in the proportion of patients from each group who disposed in a manner
      that was recommended by the brochure (43% vs 64%, p = 0.19). CONCLUSIONS:
      Dissemination of the educational brochure improved disposal of unused opioids
      after surgery. This low-cost, easily implemented intervention can improve
      disposal of unused opioids and ultimately, decrease the amount of excess opioids
      circulating in our communities.

PMID- 29331348
TI  - Effects of l-tryptophan on the growth, intestinal enzyme activities and non
      specific immune response of sea cucumber (Apostichopus japonicus Selenka) exposed
      to crowding stress.
AB  - In order to reveal the effects of l-tryptophan (Trp) on the physiology and immune
      response of sea cucumber (Apostichopus japonicus Selenka) exposed to crowding
      stress, four density groups of sea cucumbers (i.e. 4, 8, 16 and 32 individuals
      per 40 L water, represented as L, ML, MH and H) were fed with diets containing 0,
      1, 3 and 5% l-tryptophan respectively for 75 days. The results showed that the
      specific growth rates (SGR) of the sea cucumber fed with diet with 3% Trp (L,
      2.1; ML, 1.76; MH, 1.2; H, 0.7) were significantly higher than those fed with
      basal diet without Trp supplementation (P < .05). Peak amylase activity occurred
      at H stress density at 3% dietary Trp. Trypsin activity was higher in diet 3% in
      ML and MH densities than the controls, which increased by 66.4% and 53.8%.
      However, the lipase activity first increased and then decreased from the stocking
      density L to H, with highest values of 3% Trp group showed the highest value than
      other groups. Compared to those fed with the basal diet, sea cucumber fed diets
      with Trp (3%) had significantly higher phagocytic activities (0.28 OD540/106
      cells, H) in coelomic fluid and respiratory burst activities (0.105 OD630/106
      cells, MH) (P < .05). The results suggested that Trp cannot improve superoxide
      dismutase (SOD) activity at L, ML and MH densities. The alkaline phosphatase
      activity (AKP) significantly decreased at H stress density. Under the
      experimental conditions, the present results confirmed that a diet supplemented
      with 3% Trp was able to enhance intestinal enzyme activities, non-specific immune
      response and higher growth performance of A. japonicus.

PMID- 29331349
TI  - Effect of a LECT2 on the immune response of peritoneal lecukocytes against Vibrio
      anguillarum in roughskin sculpin.
AB  - Leukocyte cell-derived chemotaxin 2 (LECT2) is a multi-functional protein that is
      mainly synthesized by the liver. However, its role in roughskin scalping is less
      known. Here, we cloned a leukocyte cell-derived chemotaxin 2 (TfLECT2) genes in
      the liver of roughskin scalping, Trachidermus fasciatus, and studied its possible
      role involved in the immune response against Vibrio anguillarum (V. anguillarum)
      of peritoneal lecukocytes under in vivo conditions. The cDNA sequence of TfLECT2
      is 566 bp in size. Its deduced amino acid (aa) sequence comprises 151 residues,
      of which the first 16 residues form a putative signal peptide and 101 residues
      compose a typical peptidase M23 domain in the C-terminal region. The domain
      structure is conserved in all LECT2 proteins, which suggests a close phylogenetic
      relationship between TfLECT2 and LECT2 in other fish species. Real-time
      quantitative PCR analysis revealed that TfLECT2 gene expression was dramatically
      increased in liver after V. anguillarum stimulation. Subsequently, TfLECT2 was
      prokaryotic expressed and purified to prepare anti-TfLECT2 antibody. After V.
      anguillarum challenge, leukocytes recruitment and LECT2 levels in peritoneal
      exudates were increased, and positively correlated with each other. Moreover,
      recombinant TfLECT2 administration significantly improved immune responses after
      infection, principally in stimulating the recruitment, phagocytosis and
      respiratory burst of leukocytes at the site of infection; however, anti-TfLECT2
      treatment neutralized these abilities. Therefore, TfLECT2 may trigger the early
      immune events of peritoneal leukocytes and it will be useful to induce innate
      immune response of fish.

PMID- 29331350
TI  - Construction of pOGOduet - An inducible, bicistronic vector for synthesis of
      recombinant proteins in Corynebacterium glutamicum.
AB  - The Gram-positive Corynebacterium glutamicum is widely known for its application
      in the industrial production of amino acids and as a non-pathogenic model
      organism for cell wall biosynthesis in the group of CMN bacteria. For
      biotechnological and physiological studies often co-expression of recombinant
      genes is required, however for C. glutamicum no vector for the independent co
      expression of two genes was described. We here created the novel expression
      vector pOGOduet for C. glutamicum, which carries the ColE1 replicon of E. coli
      and the pBL1 replicon of C. glutamicum and two independently inducible promoters
      Ptac and Ptet each followed by unique multiple cloning sites. Functionality of
      pOGOduet is tested by coexpression of genes for the fluorescent proteins eCFP and
      mVenus; fluorescence of the reporters varies in dependence of the inducer
      concentrations present in the culture broth. These experiments demonstrate that
      the vector pOGOduet fulfills the task for individually inducible expression of
      two genes of interest in C. glutamicum.

PMID- 29331351
TI  - Endoscopic surgery of the frontoethmoidal osteomas.

PMID- 29331352
TI  - Factors associated with voice disorders among the elderly: a systematic review.
AB  - INTRODUCTION: During the aging process, natural modifications occur in the larynx
      and the structures involved in phonation which explain the specific
      characteristics found in the voices of elderly persons. When, at any moment, a
      voice fails and there is interference with communication, a voice disorder has
      occurred. This can generate disadvantages in communicative efficiency and have a
      negative impact on quality of life, compromising mechanisms of socialization, the
      maintenance of autonomy, and the sense of well-being. Nevertheless, there appears
      to be little clarity about which factors are associated with voice disorders in
      this population, especially from an epidemiological perspective. OBJECTIVE: The
      present study is a literature review to identify factors associated with voice
      disorders among the elderly described in population-based studies. METHODS: A
      systematic review of electronic databases was carried out. The methodological
      quality of the studies was analyzed with the Strengthening the Reporting of
      Observational Studies in Epidemiology guidelines. The research was conducted
      independently by two researchers. RESULTS: Although two articles met the
      eligibility criteria, none fulfilled all the criteria for the evaluation of
      methodological quality. According to the two studies selected for this review,
      factors associated with voice disorders among the elderly included both physical
      and psychosocial aspects. However, the methodological discrepancies between the
      studies, particularly in relation to sample selection and the instruments used
      indicate great variability and compromise the reliability of the results.
      CONCLUSION: Further prevalence studies and investigations of factors associated
      with voice disorders in the elderly from an epidemiological perspective, and
      which involve different cultures, should be carried out.

PMID- 29331353
TI  - Mechanisms of Sex Differences in Fear and Posttraumatic Stress Disorder.
AB  - Following sexual maturity, females disproportionately have higher rates of
      posttraumatic stress disorder (PTSD) and experience greater symptom severity and
      chronicity as compared with males. This observation has led many to examine sex
      differences in PTSD risk factors. Though relatively few, these studies reveal
      that the root causes of PTSD sex differences are complex, and partly represent
      interactions between sex-specific nonbiological and biological risk factors,
      which differentially shape PTSD vulnerability. Moreover, these studies suggest
      that sex-specific PTSD vulnerability is partly regulated by sex differences in
      fear systems. Fear, which represents a highly conserved adaptive response to
      threatening environmental stimuli, becomes pathological in trauma- and stress
      based psychiatric syndromes, such as PTSD. Over the last 30 years, considerable
      progress has been made in understanding normal and pathological molecular and
      behavioral fear processes in humans and animal models. Thus, fear mechanisms
      represent a tractable PTSD biomarker in the study of sex differences in fear. In
      this review, we discuss studies that examine nonbiological and biological sex
      differences that contribute to normal and pathological fear behaviors in humans
      and animal models. This, we hope, will shed greater light on the potential
      mechanisms that contribute to increased PTSD vulnerability in females.

PMID- 29331354
TI  - Specificity in Etiology of Subtypes of Bipolar Disorder: Evidence From a Swedish
      Population-Based Family Study.
AB  - BACKGROUND: Uncertainty remains whether bipolar I disorder (BDI) and bipolar II
      disorder (BDII) differ etiologically. We used a population-based family sample to
      examine the etiological boundaries between BDI and BDII by assessing their
      familial aggregation/coaggregation and by assessing the coaggregation between
      them and schizophrenia, depression, attention-deficit/hyperactivity disorder,
      eating disorders, autism spectrum disorder, substance use disorders, anxiety
      disorders, and personality disorders. METHODS: By linking Swedish national
      registers, we established a population-based cohort (N = 15,685,511) and
      identified relatives with different biological relationships. Odds ratios (ORs)
      were used to measure the relative risk of BDI and BDII in relatives of
      individuals diagnosed with BDI (n = 4309) and BDII (n = 4178). The heritability
      for BDI and BDII and the genetic correlation across psychiatric disorders were
      estimated by variance decomposition analysis. RESULTS: Compared with the general
      population, the OR of BDI was 17.0 (95% confidence interval [CI] 13.1-22.0) in
      first-degree relatives of BDI patients, higher than that of BDII patients (OR
      9.8, 95% CI 7.7-12.5). The ORs of BDII were 13.6 (95% CI 10.2-18.2) in first
      degree relatives of BDII patients and 9.8 (95% CI 7.7-12.4) in relatives of BDI
      patients. The heritabilities for BDI and BDII were estimated at 57% (95% CI 32%
      79%) and 46% (95% CI 21%-67%), respectively, with a genetic correlation estimated
      as 0.78 (95% CI 0.36-1.00). The familial coaggregation of other psychiatric
      disorders, in particular schizophrenia, showed different patterns for BDI and
      BDII. CONCLUSIONS: Our results suggest a distinction between BDI and BDII in
      etiology, partly due to genetic differences.

PMID- 29331355
TI  - Contemporary Procedural Complications, Hospitalizations, and Emergency Visits
      After Catheter Ablation for Atrial Fibrillation.
AB  - Contemporary data on complications and resource utilization after atrial
      fibrillation (AF) ablation are limited. We evaluated rates and risk factors for
      procedural complication, rehospitalization, and emergency department visits after
      AF ablation. We identified all adult patients who underwent isolated AF ablation
      between 2010 and June 2014 in 2 large integrated health-care delivery systems and
      evaluated rates of acute inpatient complication, 30-day, and 1-year readmission
      and emergency evaluation. We used multivariable logistic regression to identify
      predictors of procedural complications, 30-day readmission, or 30-day emergency
      department evaluation. In 811 AF ablation patients, procedural complications
      occurred in 2.5% of patients, 9.7% of patients were rehospitalized within 30
      days, and 19.1% of patients had an emergency visit within 30 days. At 1 year
      after AF ablation, 28.9% of patients were readmitted, with 18% of patients
      readmitted for AF or atrial flutter. At 1 year, 44.5% of patients were seen in an
      emergency department, with 37.1% related to AF or atrial flutter. Vascular
      complications and perforation or tamponade were the most common complications,
      and Hispanic ethnicity, mitral or aortic valvular disease, and diabetes mellitus
      were the strongest risk factors for adverse outcomes at 30 days after AF
      ablation. Contemporary rates of acute complication and 1-year readmission after
      AF ablation have markedly decreased compared with previous community-based
      studies.

PMID- 29331357
TI  - Differentiation of Inflammatory From Fibrotic Ileal Strictures among Patients
      with Crohn's Disease Based on Visual Analysis: Feasibility Study Combining
      Conventional B-Mode Ultrasound, Contrast-Enhanced Ultrasound and Strain
      Elastography.
AB  - The aim of this pilot study was to assess prospectively the feasibility of
      conventional B-mode ultrasound (US) and contrast-enhanced ultrasound (CEUS)
      combined with real-time strain elastography (SE) in the differentiation of
      inflammatory from fibrotic ileal strictures among patients with Crohn's disease
      (CD) based on visual analysis. Twenty non-consecutive patients (15 male and 5
      female; mean age +/- standard deviation, 40.2 +/- 10.22 y) with CD and stricture
      of the terminal ileal loop were scanned by conventional B-mode US and CEUS and,
      subsequently, by real-time SE. Two independent readers visually classified each
      bowel stricture as fibrotic or inflammatory based on conventional B-mode US,
      CEUS, SE, individually and then for all techniques combined. All techniques
      combined had a higher (p <0.05) sensitivity (reader 1, 9/20 [45%]; reader 2, 7/20
      [35%]), specificity (reader 1, 5/20 [25%]; reader 2, 8/20 [40%]) and diagnostic
      accuracy (reader 1, 14/20 [70%]; reader 2, 15/20 [75%]) and higher (p <0.05) area
      under the receiver operating characteristic curve (reader 1, 0.953; reader 2,
      0.921) than individual techniques. Inter-reader agreement was fair for
      conventional B-mode US (k = 0.46) and CEUS (k = 0.39), moderate for SE (k = 0.6)
      and fair for all techniques combined (k = 0.38). Conventional B-mode US and CEUS,
      in combination with SE, may improve differentiation of inflammatory from fibrotic
      ileal strictures among patients with CD based on visual analysis.

PMID- 29331356
TI  - Assessment of Diastolic Function Using Ultrasound Elastography.
AB  - Shear wave elasticity imaging (SWEI) is a novel ultrasound elastography technique
      for assessing tissue stiffness. In this study, we investigate the potential of
      SWEI for providing diastolic functional assessment. In 11 isolated rabbit hearts,
      pressure-volume (PV) measurements were recorded simultaneously with SWEI
      recordings from the left ventricle free wall before and after induction of global
      ischemia. PV-based end diastolic stiffness increased by 100% after ischemia (p
      <0.05), and SWEI stiffness showed an increase of 103% (p <0.05). The relaxation
      time constant (tau) before and after ischemia derived from pressure and SWEI
      curves showed increases of 79% and 76%, respectively (p <0.05). A linear
      regression between pressure-derived and SWEI-based (tau) showed a slope of 1.164
      with R2 = 0.80, indicating the near equivalence of the two assessments. SWEI can
      be used to derive (tau) values and myocardial end diastolic stiffness. In global
      conditions, these measurements are consistent with PV measurements of diastolic
      function.

PMID- 29331358
TI  - Assessing Risk Category of Breast Cancer by Ultrasound Imaging Characteristics.
AB  - The purpose of our study was to assess the potential clinical value of ultrasound
      imaging in predicting risk category in patients with breast cancer. Three hundred
      thirty-six patients were enrolled and divided into a high-risk group (99, 29.5%)
      and mid- to low-risk group (237, 70.5%) according to the St. Gallen risk
      criteria. All data were retrospectively collected to analyze correlations between
      ultrasound features and risk category. The results revealed that the ultrasound
      features of irregular shape (p= 0.002), vertical growth orientation (p= 0.002),
      angular contour (p= 0.022) and high color Doppler flow imaging grade (p= 0.001)
      tended to be present in images of the high-risk group. Therefore, tumor
      ultrasound features should be recognized as an ideal option for determination of
      risk category in patients with breast cancer.

PMID- 29331359
TI  - Quantitative CT Evaluation of Small Pulmonary Vessels in Patients with Acute
      Pulmonary Embolism.
AB  - RATIONALE AND OBJECTIVES: The objective of this study was to investigate the
      correlation between the computed tomography (CT) cross-sectional area (CSA) of
      small pulmonary vessels and the CT obstruction index in patients with acute
      pulmonary embolism (PE) and the correlation between the changes in these
      measurements after anticoagulant therapy. MATERIALS AND METHODS: Fifty-two
      patients with acute PE were selected for this study. We measured the CSA less
      than 5 mm2 on coronal reconstructed images to obtain the percentage of the CSA
      (%CSA < 5). CT angiographic index was obtained based on the Qanadli method for
      the evaluation of the degree of pulmonary arterial obstruction. Spearman rank
      correlation analysis was used to evaluate the relationship between the initial
      and the follow-up values and changes in the %CSA < 5 and the CT obstruction
      index. RESULTS: There was no significant correlation between the %CSA < 5 and CT
      obstruction index on both initial (rho = -0.03, P = 0.84) and follow-up (rho = 
      0.03, P = 0.82) assessments. In contrast, there was a significant negative
      correlation between the changes in %CSA < 5 and the CT obstruction index (rho = 
      0.59, P < 0.0001). CONCLUSIONS: Although the absolute %CSA < 5 and CT obstruction
      index were not significantly correlated, the changes in the values of the two
      parameters had a significant correlation. Changes in %CSA < 5, which can be
      obtained easily, can be used as biomarker of therapeutic response in patients
      with acute PE.

PMID- 29331360
TI  - Fully Automated Segmentation of Polycystic Kidneys From Noncontrast Computed
      Tomography: A Feasibility Study and Preliminary Results.
AB  - RATIONALE AND OBJECTIVES: Total kidney volume is an important biomarker for the
      evaluation of autosomal dominant polycystic kidney disease progression. In this
      study, we present a novel approach for automated segmentation of polycystic
      kidneys from non-contrast-enhanced computed tomography (CT) images. MATERIALS AND
      METHODS: Non-contrast-enhanced CT images were acquired from 21 patients with a
      diagnosis of autosomal dominant polycystic kidney disease. Kidney volumes
      obtained from the fully automated method were compared to volumes obtained by
      manual segmentation and evaluated using linear regression and Bland-Altman
      analyses. Dice coefficient was used for performance evaluation. RESULTS: Kidney
      volumes from the automated method well correlated with the ones obtained by
      manual segmentation. Bland-Altman analysis showed a low percentage bias (-0.3%)
      and narrow limits of agreements (11.0%). The overlap between the three
      dimensional kidney surfaces obtained with our approach and by manual tracing,
      expressed in terms of Dice coefficient, showed good agreement (0.91 +/- 0.02).
      CONCLUSIONS: This preliminary study showed the proposed fully automated method
      for renal volume assessment is feasible, exhibiting how a correct use of
      biomedical image processing may allow polycystic kidney segmentation also in non
      contrast-enhanced CT. Further investigation on a larger dataset is needed to
      confirm the robustness of the presented approach.

PMID- 29331361
TI  - Uterine Artery Embolization: An Analysis of Online Patient Information Quality
      and Readability with Historical Comparison.
AB  - RATIONALE AND OBJECTIVES: Investigators aimed to assess online information
      describing uterine artery embolization (UAE) to examine the quality and
      readability of websites patients are accessing. MATERIALS AND METHODS: A list of
      applicable, commonly used searchable terms was generated, including "Uterine
      Artery Embolization," "Fibroid Embolization," "Uterine Fibroid Embolization," and
      "Uterine Artery Embolisation." Each possible term was assessed across the five
      most-used English language search engines to determine the most commonly used
      term. The most common term was then investigated across each search engine, with
      the first 25 pages returned by each engine included for analysis. Duplicate
      pages, nontext content such as video or audio, and pages behind paywalls were
      excluded. Pages were analyzed for quality and readability using validated tools
      including DISCERN score, JAMA Benchmark Criteria, HONcode Certification, Flesch
      Reading Ease Score, Flesch-Kincaid Grade Level, and Gunning-Fog Index. Secondary
      features such as age, rank, author, and publisher were recorded. RESULTS: The
      most common applicable term was "Uterine Artery Embolization" (492,900 results).
      Mean DISCERN quality of information provided by UAE websites is "fair"; however,
      it has declined since comparative 2012 studies. Adherence to JAMA Benchmark
      Criteria has reduced to 6.7%. UAE website readability remains more difficult than
      the World Health Organization-recommended 7-8th grade reading levels. HONcode
      certified websites (35.6%) demonstrated significantly higher quality than
      noncertified websites. CONCLUSIONS: Quality of online UAE information remains
      "fair." Adherence to JAMA benchmark criteria is poor. Readability is above
      recommended 7-8th grade levels. HONcode certification was predictive of higher
      website quality, a useful guide to patients requesting additional information.

PMID- 29331362
TI  - Multi-model Analysis of Diffusion-weighted Imaging of Normal Testes at 3.0 T:
      Preliminary Findings.
AB  - RATIONALE AND OBJECTIVES: This study aimed to establish diffusion quantitative
      parameters (apparent diffusion coefficient [ADC], DDC, alpha, Dapp, and Kapp) in
      normal testes at 3.0 T. MATERIALS AND METHODS: Sixty-four healthy volunteers in
      two age groups (A: 10-39 years; B: >= 40 years) underwent diffusion-weighted
      imaging scanning at 3.0 T. ADC1000, ADC2000, ADC3000, DDC, alpha, Dapp, and Kapp
      were calculated using the mono-exponential, stretched-exponential, and kurtosis
      models. The correlations between parameters and the age were analyzed. The
      parameters were compared between the age groups and between the right and the
      left testes. RESULTS: The average ADC1000, ADC2000, ADC3000, DDC, alpha, Dapp,
      and Kapp values did not significantly differ between the right and the left
      testes (P > .05 for all). The following significant correlations were found:
      positive correlations between age and testicular ADC1000, ADC2000, ADC3000, DDC,
      and Dapp (r = 0.516, 0.518, 0.518, 0.521, and 0.516, respectively; P < .01 for
      all) and negative correlations between age and testicular alpha and Kapp (r = 
      0.363, -0.427, respectively; P < .01 for both). Compared to group B, in group A,
      ADC1000, ADC2000, ADC3000, DDC, and Dapp were significantly lower (P < .05 for
      all), but alpha and Kapp were significantly higher (P < .05 for both).
      CONCLUSIONS: Our study demonstrated the applicability of the testicular mono
      exponential, stretched-exponential, and kurtosis models. Our results can help
      establish a baseline for the normal testicular parameters in these diffusion
      models. The contralateral normal testis can serve as a suitable reference for
      evaluating the abnormalities of the other side. The effect of age on these
      parameters requires further attention.

PMID- 29331363
TI  - Breast Imaging Match Highlights the Need to Unify the Approach to Fellowship.

PMID- 29331364
TI  - Picky eating, pressuring feeding, and growth in toddlers.
AB  - Several common theoretical frameworks have posited causal pathways between picky
      eating, pressuring feeding, and growth in early childhood. The evidence to
      support these pathways is limited. This observational cohort study sought to
      examine the cross-lagged associations between mother-reported pressuring feeding,
      mother-reported child picky eating, and measured weight-for-length z-score (WLZ)
      across child ages 21, 27, and 33 months (n = 244). Cross-lagged analysis was used
      to evaluate longitudinal associations between these three constructs. The sample
      was 50.5% white, 52.3% male and 37.8% of mothers had a high school education or
      less. Mean WLZ was 0.52, 0.41, and 0.38 at each age, respectively. Pressuring
      feeding, picky eating, and WLZ each tracked strongly from 21 to 33 months. There
      were concurrent associations between pressuring feeding and picky eating.
      However, there were no prospective associations between pressuring feeding and
      future WLZ; WLZ and future pressuring feeding; pressuring feeding and future
      picky eating; picky eating and future pressuring feeding; or picky eating and
      future WLZ. Our results do not support causal relationships between picky eating,
      pressuring feeding, and growth in toddlerhood. Future work that examines
      alternative mechanisms shaping growth in early childhood is needed.

PMID- 29331365
TI  - Assessment of test-retest reliability of a food choice task among healthy
      individuals.
AB  - Aberrations in eating patterns constitute a substantial public health burden.
      Computer-based paradigms that measure responses to images of foods are
      potentially useful tools for assessing food attitudes and characteristics of
      eating behavior. In particular, food choice tasks attempt to directly probe
      aspects of individuals' decisions about what to eat. In the Food Choice Task
      participants rate the healthiness and tastiness of a variety of food items
      presented one at a time. Next, participants choose for each food item whether
      they prefer to eat the item vs. a neutrally rated reference food item. The goal
      of the current study was to assess the stability and reliability of this Food
      Choice Task over time and with repeated testing. Secondary analyses were
      conducted using data from healthy volunteers in two separate studies that
      administered the task at two time points, separated either by several days or
      about a month. The overall reliability of the Food Choice Task across multiple
      administrations was assessed using intra-class correlation coefficients and the
      reliability of ratings of individual food items was assessed using kappa
      coefficients. The results indicated that test-retest reliability of the Food
      Choice Task in healthy volunteers was high at both shorter and longer test-retest
      intervals. In addition, the reliability of individual food item ratings was good
      for a majority of items. The proportion of healthy volunteers' high-fat food
      choices did not change over time in either of the two studies. Thus, the Food
      Choice Task is suitable for measuring food choices in studies with multiple
      assessment points. In particular, the task may be well suited to assess
      restrictive eating, a construct which it has been difficult to assess in
      experimental settings.

PMID- 29331366
TI  - Eating in the absence of hunger is related to loss-of-control eating, hedonic
      hunger, and short-term weight gain in normal-weight women.
AB  - Eating beyond physiological need contributes to obesity onset. Measuring this
      behavior could help identify those at risk for weight gain. This study measured
      eating in the absence of hunger (EAH) and its relationship with weight change and
      self-report measures related to appetite and eating behavior. EAH was assessed in
      46 lean young women (69% pre-selected for weight gain proneness) after lunch and
      defined as the number of calories subsequently consumed from snacks. Participants
      also completed questionnaires, and their body weights were measured regularly
      over the next year. Participants consumed a mean 188 calories (+/-140) during the
      EAH test. Caloric intake during the EAH test was associated with hedonic hunger
      (p < .01, R2 = 0.18), loss of control eating (p < .001, R2 = 0.29), and weight
      gain over two months (p < .01, R2 = 0.19), controlling for baseline body mass
      index. All were large effect sizes. In contrast, EAH was unrelated to emotional
      eating, disinhibition, and longer-term weight change. Amount of the test meal
      eaten in a hungry state was unrelated to these variables. While EAH has mainly
      been examined in children, these results expand its utility to adults. EAH seems
      to reflect naturalistic eating behavior, as shown by its relationship with short
      term weight gain, drive to overconsume foods, and loss of control over eating.
      EAH may be a useful test to identify young adults at risk for weight gain and/or
      disordered eating, and may be a target for intervention.

PMID- 29331367
TI  - Molecular characterization and differential expression analysis of interleukin
      1beta from Ovis aries.
AB  - The interleukin-1 family is an important component of the innate immune system
      and plays an important role in regulating immune responses on the invasion of
      intracellular parasites in the acquired immune system. Interleukin 1beta (IL
      1beta) is one of the members of the IL-1 family that predominantly activates
      downstream signaling pathways to play immunological functions of stimulating T
      and B lymphocyte activation and promoting the various syntheses of inflammatory
      substances in conjunction with other cytokines. Here, a full-length IL-1beta cDNA
      (OaIL-1beta) of sheep (Ovis aries) was cloned using rapid amplification of cDNA
      ends (RACE), which consists of 1494 bp and contains a 5'-UTR region with a length
      of 83 bp, a complete ORF of 801 bp in length, and a 3'-UTR region with a length
      of 642 bp. Recombinant protein OaIL-1beta was expressed and purified, and the
      monoclonal antibody against IL-1beta of sheep is prepared. Western blotting
      results showed that the sheep IL-1beta protein was detected in the heart, liver,
      lung, kidney, stomach, intestine, muscle, lymph nodes and leukocytes with the
      highest expression in the muscle and the lowest expression in the lung. Different
      bacteria treating sheep white blood cells induced differential expression of OaIL
      1beta. Compared with the normal sheep, OaIL-1beta in the buffy coat was
      differentially expressed in the Brucella melitensis-challenged group and the B.
      suis S2 strain-inoculated group. However, whether IL-1beta may be considered as a
      molecular biomarker for differing Brucella-infected animals from brucellosis
      vaccinated animals or not need to be further studied.

PMID- 29331368
TI  - In vitro and in vivo safety analysis of Enterococcus faecium 2C isolated from
      human breast milk.
AB  - INTRODUCTION: Safety analysis of probiotic bacteria is an obligatory
      characteristic to be evaluated prior to application in food or pharmacological
      products. This study was designed to evaluate in vitro and in vivo safety
      parameters of Enterococcus faecium 2C strain, a probiotic candidate isolated from
      human breast milk. MATERIAL AND METHODS: E.faecium 2C was studied for its
      hemolytic activity and phenotypic antibiotics resistance profile. In vivo safety
      of the mentioned Enterococcus strain was studied by determining acute oral
      toxicity in Wistar Male rats. The animals were randomly divided into two groups
      of 3 animals each. The test group animals were gavaged daily with bacterial dose
      of 1 * 1011 CFU/kg of animal body weight for 21 consecutive days. The animals in
      control group received normal basal diet without any supplementations.
      Hematological and biochemical parameters, organ weight, body weight and common
      health features of the animals were recorded. RESULTS: E.faecium 2C appeared non
      hemolytic and sensitive to the majority of the tested antibiotics. The Wistar
      male rats fed orally with the mentioned bacterial suspensions survived the test
      period, and showed normal growth and development. No adverse effects on the
      general health condition, behavior, and growth were seen in the treated animals
      compared to control group. Additionally, no significant changes in the
      hematological results, blood biochemistry, organ weights and histopathology of
      the rats in treatment groups were observed. None of the vital organs of the
      treated animals showed signs of bacteremia or infectivity. CONCLUSION: E.faecium
      2C strain isolated from human breast milk might be considered safe for use in
      probiotic formulations intended for man and animals.

PMID- 29331369
TI  - Equisetum telmateia extracts: Chemical compositions, antioxidant activity and
      antimicrobial effect on the growth of some pathogenic strain causing poisoning
      and infection.
AB  - The aerial parts of Equisetum telmateia have been used as a source of
      biologically active compounds to treat inflammatory, diarrhea, stomach-ache,
      eczema and mouth infections in traditional medicine. The aim of this work is to
      evaluate the extraction yield, chemical compositions, antioxidant activity and
      antimicrobial activity of E. telmateia extracts on Staphylococcus aureus,
      Bacillus cereus, Escherichia coli, Salmonella typhi and Candida albicans.
      Chemical compositions E. telmateia was analyzed by high performance liquid
      chromatography (HPLC) using a C18 column. Analysis of E. telmateia extract by
      HPLC allowed the identification of Kaempferol 3-O-(6"-O-acetylglucoside) as major
      compound. The antioxidant activity of extracts was examined by measuring their
      ability to sequestrate 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals. The results
      showed that the DPPH (IC50 = 70.83 +/- 0.2 MUg/ml) were obtained in the case of
      supercritical fluid extraction (SFE) extract. MIC microdilution assay were used
      to determine the antimicrobial activities. Contrary to lower extraction yield
      (9.6 +/- 0.5), the SFE extract exhibited the highest antimicrobial potency with
      MIC and MBC values of 32 mg/ml against S. aureus compared to the other extracts.
      The results suggest that SFE method is more appropriate for extraction of E.
      telmateia biologically active substances with antimicrobial and antioxidant
      activity than conventional solvent extraction methods.

PMID- 29331370
TI  - Preparation and evaluation of antibacterial potential of Pithecellobium dulce
      root extract against Gram positive and Gram negative bacteria.
AB  - In the present study hexane, benzene, ethyl acetate and ethanol extracts of
      Pithecellobium dulce root were prepared using soxhlet extractor. The extracts
      were evaluated for antibacterial activity against one Gram positive
      (Staphylococcus aureus) and three Gram negative (Acetobacter aceti, Acetobacter
      aceti, Klebsiella pneumoniae) strains. Disc diffusion method revealed promising
      antibacterial activity of the extracts prepared in polar solvents (ethyl acetate
      and ethanol) compared to non-polar solvents (hexane and benzene). Ethanolic root
      extract was found to be most active against Acetobacter aceti, Staphylococcus
      aureus, Klebsiella pneumonia and Enterobacter aerogenes bacterial strains. The
      zone of inhibition of ethanolic root extract against Acetobacter aceti,
      Staphylococcus aureus, Klebsiella pneumonia and Enterobacter aerogenes bacterial
      strains was 15.4, 11.0, 19.0 and 13.0 mm, respectively at 100 mg concentration.
      Ethyl acetate extract also exhibited good antibacterial activity against
      Entrobacter aerogenes, Klebsiella pneumonia and Acetobacter aceti. The zone of
      inhibition of ethyl acetate root extracts against Entrobacter aerogenes,
      Acetobacter aceti and Klebsiella pneumonia was 10.5, 18.0 and 10.0 mm,
      respectively. The benzene extract showed some activity against Acetobacter aceti
      with the zone of inhibition 10.0 mm. The antibacterial activity of Pithecellobium
      dulce root hexane extract was found to be negligible against all the four tested
      strains of bacteria. These findings suggest that ethanolic and ethyl acetate root
      extracts of Pithecellobium dulce has potential as effective anti-bacterial agent.

PMID- 29331372
TI  - Cancer care delivery research in gynecologic oncology.

PMID- 29331371
TI  - Birth weight and the risk of histological subtypes of ovarian and endometrial
      cancers: Results from the Copenhagen School Health Records Register.
AB  - BACKGROUND: Studies of birth weight associations with ovarian and endometrial
      cancer risks are limited with inconsistent results, and none has evaluated
      associations by histologic subtype. We utilized prospectively collected birth
      weight information to investigate the association with risk of ovarian and
      endometrial cancers overall and by histologic subtype. METHODS: 162,559 girls,
      born from 1930 to 1989, from the Copenhagen School Health Records Register
      (CSHRR) were followed prospectively via linkage with the Danish health registers.
      Ovarian (n=666) and endometrial (n=694) cancers were identified from 1978 to
      2014. Cox regression was used to estimate hazard ratios (HR) and 95% confidence
      intervals (CI). RESULTS: Women with lower (2.0-3.25 vs. 3.26-3.75kg) and higher
      (3.75-5.5 vs. 3.26-3.75kg) birth weights had increased risks of ovarian cancer
      overall [HR (95% CI): 1.27 (1.06-1.52); 1.51 (1.21-1.87), respectively] and
      serous ovarian cancers [1.54 (1.19-1.98); 1.98 (1.47-2.67), respectively]. A
      decreased risk of Type II endometrial tumors was suggested per kilogram increase
      in birth weight [HR (95% CI): 0.63 (0.40-1.00)]. CONCLUSIONS: Our results suggest
      that both lower and higher birth weights were associated with increased ovarian
      cancer risk and associations were particularly strong for serous ovarian cancer,
      the most common subtype. Birth weight was not associated with most types of
      endometrial cancer.

PMID- 29331374
TI  - Alternative pathway of H2S and polysulfides production from sulfurated catalytic
      cysteine of reaction intermediates of 3-mercaptopyruvate sulfurtransferase.
AB  - It has been known that hydrogen sulfide and/or polysulfides are produced from a
      (poly)sulfurated sulfur-acceptor substrate of 3-mercaptopyruvate
      sulfurtransferase (MST) via thioredoxin (Trx) reduction in vitro. In this study,
      we used thiosulfate as the donor substrate and the catalytic reaction was
      terminated on the formation of a persulfide or polysulfides. We can present
      alternative pathway of production of hydrogen sulfide and/or polysulfides from
      (poly)sulfurated catalytic-site cysteine of reaction intermediates of MST via Trx
      reduction. Matrix-assisted laser desorption ionization tandem time-of-flight mass
      spectrometric analysis revealed that after prolonged incubation of MST with
      thiosulfate, a trisulfide adduct becomes predominant at the sulfurated catalytic
      site cysteine. When these adducts were reduced by Trx with reducing system
      (MST:Escherichia coli Trx:E. coli Trx reductase:NADPH = 1:5:0.02:12.5 molar
      ratio), liquid chromatography with tandem mass spectrometric analysis for
      monobromobimane-derivatized H2Sn revealed that H2S2 first appeared, and then H2S
      and H2S3 did later. The results were confirmed by high-performance liquid
      chromatography-fluorescence analysis.

PMID- 29331373
TI  - Establishment and characterization of five immortalized human scalp dermal
      papilla cell lines.
AB  - Dermal papilla (DP) regulates the growth and cycling of hair follicles. Cultured
      DP cells are useful for the study of their role in relation to hair growth and
      regeneration. However, cultivation of human DP cells is tedious and difficult. In
      addition, cultured DP cells possess a relatively short replicative life span,
      requiring immortalized human DP cell lines. We previously established an
      immortalized human DP cell line, SV40T-hTERT-DPC, by introducing human telomerase
      reverse transcriptase (hTERT) gene into the transformed cell line, SV40T-DPC. In
      this study, we co-transfected the simian virus 40 large T antigen (SV40T-Ag) and
      hTERT into DP cells from scalp hair follicles from a male with androgenetic
      alopecia and established five immortalized DP cell lines and named KNU-101, KNU
      102, KNU-103, KNU-201 and KNU-202. We then evaluated tumorigenicity, expression
      of DP markers, responses to androgen, Wnt3a and BMP4, and expression of DP
      signature genes. These cell lines displayed early passage morphology and
      maintained responses to androgen, Wnt and BMP. Furthermore, these cell lines
      expressed DP markers and DP signature genes. KNU cell lines established in this
      study are potentially useful sources for hair research.

PMID- 29331375
TI  - Xanthomonas TAL effectors hijack host basal transcription factor IIA alpha and
      gamma subunits for invasion.
AB  - The Xanthomonas genus includes Gram-negative plant-pathogenic bacteria, which
      infect a broad range of crops and wild plant species, cause symptoms with leaf
      blights, streaks, spots, stripes, necrosis, wilt, cankers and gummosis on leaves,
      stems and fruits in a wide variety of plants via injecting their effector
      proteins into the host cell during infection. Among these virulent effectors,
      transcription activator-like effectors (TALEs) interact with the gamma subunit of
      host transcription factor IIA (TFIIAgamma) to activate the transcription of host
      disease susceptibility genes. Functional TFIIA is a ternary complex comprising
      alpha, beta and gamma subunits. However, whether TALEs recruit TFIIAalpha,
      TFIIAbeta, or both remains unknown. The underlying molecular mechanisms by which
      TALEs mediate host susceptibility gene activation require full elucidation. Here,
      we show that TALEs interact with the alpha+gamma binary subcomplex but not the
      alpha+beta+gamma ternary complex of rice TFIIA (holo-OsTFIIA). The transcription
      factor binding (TFB) regions of TALEs, which are highly conserved in Xanthomonas
      species, have a dominant role in these interactions. Furthermore, the interaction
      between TALEs and the alpha+gamma complex exhibits robust DNA binding activity in
      vitro. These results collectively demonstrate that TALE-carrying pathogens hijack
      the host basal transcription factors TFIIAalpha and TFIIAgamma, but not
      TFIIAbeta, to enhance host susceptibility during pathogen infection. The
      uncovered mechanism widens new insights on host-microbe interaction and provide
      an applicable strategy to breed high-resistance crop varieties.

PMID- 29331376
TI  - MicroRNA-425 facilitates pathogenic Th17 cell differentiation by targeting
      forkhead box O1 (Foxo1) and is associated with inflammatory bowel disease.
AB  - Inflammatory bowel disease (IBD) is a chronic autoimmune disease, and its
      pathogenesis remains mostly unknown. MicroRNAs (miRs) has drawn much attention as
      a crucial regulator of autoimmune diseases. In this study, we demonstrated, for
      the first time, that miR-425 was significantly up-regulated in peripheral blood
      mononuclear cells (PBMC) and mucosa of patients with IBD. In note, T helper (Th)
      17 cells were found to be the major source of miR-425 expression. Using gain-of
      function approaches, we demonstrated that miR-425 could facilitate the
      differentiation of CD4+ T cells into Th17 lineage. In addition, forkhead box O1
      (Foxo1) was identified as a novel target gene of miR-425, which was able to
      inhibit Th17 cell differentiation, and it was observed to be markedly decreased
      in PBMC and mucosa of patients with IBD. Notably, in vivo inhibition of miR-425
      significantly alleviated the disease severity of TNBS-induced colitis in mice,
      with down-regulated levels of IL-17A. Our data reveal a novel mechanism in which
      the elevated miR-425 in IBD mediates pathogenic Th17 cell generation through down
      regulation of Foxo1. In vivo blockade of miR-425 may serve as a novel therapeutic
      approach in the treatment of IBD.

PMID- 29331377
TI  - beta-cellulin promotes the proliferation of corneal epithelial stem cells through
      the phosphorylation of erk1/2.
AB  - The proliferation of corneal epithelial stem cells (CESCs) is a very important
      process in the recovery of corneal wounds. Recent studies have shown that beta
      cellulin (BC) is effective in the repair of other tissues. However, its mechanism
      of action in corneal wound healing is not yet clear. The purpose of this study
      was to investigate how BC accelerates wound healing of the cornea. Here, we
      confirmed that the proliferation of CESCs was induced at a specific concentration
      (0.2, 2 and 20 ng/mL) by treatment with BC. Markers associated with proliferation
      activity (DeltaNp63, bmi-1, abcg2) were also upregulated. In vivo experiments
      showed that the corneal wound healing rate was increased in mice. We found that
      BC stimulates the phosphorylation of the erk1/2 signaling pathway, which is
      triggered during the recovery of mouse corneal wounds. However, the inhibition of
      erk1/2 phosphorylation delayed the recovery of mouse corneal wounds in an organ
      culture assay. According to these results, BC may be a potential treatment factor
      for corneal wound healing.

PMID- 29331379
TI  - Effect of histidine on sorafenib-induced vascular damage: Analysis using novel
      medaka fish model.
AB  - BACKGROUND: Sorafenib (SFN) is an anti-angiogenic chemotherapeutic that prolongs
      survival of patients with hepatocellular carcinoma (HCC); its side effects,
      including vascular damages such as hand-foot syndrome (HFS), are a major cause of
      therapy discontinuation. We previously reported that maintenance of peripheral
      blood flow by intake of dried bonito broth (DBB) significantly prevented HFS and
      prolonged the administration period. The amino acids contained in DBB probably
      contribute to its effects, but the mechanism has not been clarified. We
      hypothesized that histidine, the largest component among the amino acids
      contained in DBB, has effects on SFN-induced vascular damage, and evaluated this
      possibility using a novel medaka fish model. METHODS: The fli::GFP transgenic
      medaka fish model has a fluorescently visible systemic vasculature. We fed the
      fish with SFN with and without histidine to compare blood flow and vascular
      structure among the differently fed models. The vascular cross-sectional area of
      each fish was measured to determine vascular diameter changes. RESULTS: Our
      results demonstrated that SFN-fed medaka developed a narrower vascular diameter.
      In addition, this narrowing was counteracted by addition of histidine to the
      medaka diet. We observed no positive effect of histidine on regeneration of cut
      vessels or on cell growth of endothelial cells and HCC cell lines. CONCLUSION: We
      proved the efficacy of the medaka model to assess vascular changes after
      administration of specific chemicals. And our results suggest that SFN causes
      vascular damage by narrowing peripheral vessel diameter, and that histidine
      effectively counteracts these changes to maintain blood flow.

PMID- 29331380
TI  - Eicosapentaenoic acid inhibits oxidation of high density lipoprotein particles in
      a manner distinct from docosahexaenoic acid.
AB  - The omega-3 fatty acid eicosapentaenoic acid (EPA) reduces oxidation of ApoB
      containing particles in vitro and in patients with hypertriglyceridemia. EPA may
      produce these effects through a potent antioxidant mechanism, which may
      facilitate LDL clearance and slow plaque progression. We hypothesize that EPA
      antioxidant effects may extend to ApoA-containing particles like HDL, potentially
      preserving certain atheroprotective functions. HDL was isolated from human plasma
      and incubated at 37  degrees C in the absence (vehicle) or presence of EPA and/or
      DHA; 5.0 or 10.0 MUM each. Samples were then subjected to copper-induced
      oxidation (10 MUM). HDL oxidation was inhibited similarly by EPA and DHA up to 1
      h. EPA (10 MUM) maintained significant HDL oxidation inhibition of 89% (0.622 +/-
      0.066 MUM MDA; p < .001) at 4 h, with continued inhibition of 64% at 14 h, vs.
      vehicle (5.65 +/- 0.06 to 2.01 +/- 0.10 MUM MDA; p < .001). Conversely, DHA (10
      MUM) antioxidant benefit was lost by 4 h. At a lower concentration (5 MUM), EPA
      antioxidant activity remained at 81% (5.53 +/- 0.15 to 1.03 +/- 0.10 MUM MDA; p <
      .001) at 6 h, while DHA lost all antioxidant activity by 4 h. The antioxidant
      activity of EPA was preserved when combined with an equimolar concentration of
      DHA (5 MUM each). EPA pretreatment prevented HDL oxidation in a dose-dependent
      manner that was preserved over time. These results suggest unique lipophilic and
      electron stabilization properties for EPA as compared to DHA with respect to
      inhibition of HDL oxidation. These antioxidant effects of EPA may enhance certain
      atheroprotective functions for HDL.

PMID- 29331378
TI  - Loss of zebrafish Smyd1a interferes with myofibrillar integrity without
      triggering the misfolded myosin response.
AB  - Sarcomeric protein turnover needs to be tightly balanced to assure proper
      assembly and renewal of sarcomeric units within muscle tissues. The mechanisms
      regulating these fundamental processes are only poorly understood, but of great
      clinical importance since many cardiac and skeletal muscle diseases are
      associated with defective sarcomeric organization. The SET- and MYND domain
      containing protein 1b (Smyd1b) is known to play a crucial role in
      myofibrillogenesis by functionally interacting with the myosin chaperones Unc45b
      and Hsp90alpha1. In zebrafish, Smyd1b, Unc45b and Hsp90alpha1 are part of the
      misfolded myosin response (MMR), a regulatory transcriptional response that is
      activated by disturbed myosin homeostasis. Genome duplication in zebrafish led to
      a second smyd1 gene, termed smyd1a. Morpholino- and CRISPR/Cas9-mediated
      knockdown of smyd1a led to significant perturbations in sarcomere structure
      resulting in decreased cardiac as well as skeletal muscle function. Similar to
      Smyd1b, we found Smyd1a to localize to the sarcomeric M-band in skeletal and
      cardiac muscles. Overexpression of smyd1a efficiently compensated for the loss of
      Smyd1b in flatline (fla) mutant zebrafish embryos, rescued the myopathic
      phenotype and suppressed the MMR in Smyd1b-deficient embryos, suggesting
      overlapping functions of both Smyd1 paralogs. Interestingly, Smyd1a is not
      transcriptionally activated in Smyd1b-deficient fla mutants, demonstrating lack
      of genetic compensation despite the functional redundancy of both zebrafish Smyd1
      paralogs.

PMID- 29331381
TI  - Clinical Outcomes of First-line Abiraterone Acetate or Enzalutamide for
      Metastatic Castration-resistant Prostate Cancer After Androgen Deprivation
      Therapy + Docetaxel or ADT Alone for Metastatic Hormone-sensitive Prostate
      Cancer.
AB  - BACKGROUND: The CHAARTED (ChemoHormonal Therapy Versus Androgen Ablation
      Randomized Trial for Extensive Disease in Prostate Cancer) and STAMPEDE (Systemic
      Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy)
      trials showed that the addition of docetaxel (D) to androgen deprivation therapy
      (ADT) prolonged longevity of men with metastatic hormone-sensitive prostate
      cancer (mHSPC). However, the impact of upfront D on subsequent therapies is still
      unexplored. As abiraterone acetate (AA) and enzalutamide (E) are the most
      commonly used first-line treatment for metastatic castration-resistant prostate
      cancer (mCRPC), we aimed to assess whether they maintained their efficacy after
      ADT+D versus ADT alone. PATIENTS AND METHODS: A cohort of patients with mCRPC
      treated between 2014 and 2017 with first-line AA or E for mCRPC was identified
      from 3 hospitals' institutional review board-approved databases. Patients were
      classified by use of D for mHSPC. This time frame was chosen as ADT+D became a
      valid therapeutic option for mHSPC in 2014, and it inherently entailed a short
      follow-up time on AA/E. The endpoints included overall survival from ADT start,
      overall survival from AA/E start, and time to AA/E start from ADT start.
      Differences between groups were assessed using the log-rank test. RESULTS: Of the
      102 patients with mCRPC identified, 50 (49%) had previously received ADT alone,
      while 52 (51%) had ADT+D. No statistically significant difference in any of the
      evaluated outcomes was observed between the 2 cohorts. Yet, deaths in the ADT+D
      group were 12 versus 21 in the ADT alone, after a median follow-up of 24.4 and
      29.8 months, respectively. CONCLUSION: In a cohort of ADT/ADT+D-treated patients
      with mCRPC with short times to first-line AA/E and follow-up, the efficacy of
      AA/E is similar regardless of previous use of D.

PMID- 29331382
TI  - Improved Human Pharmacokinetic Prediction of Hepatically Metabolized Drugs With
      Species-Specific Systemic Clearance.
AB  - Accurate prediction of human pharmacokinetics (PK) is important for the choice of
      promising compounds in humans. As the predictability of human PK by an empirical
      approach is low for drugs with species-specific PK, the utility of a
      physiologically based pharmacokinetic (PBPK) model was verified using 16
      hepatically metabolized reference drugs. After the prediction method for total
      clearance (CLtot) and distribution volume at steady state (Vdss) in the
      conventional PBPK model had been optimized, plasma concentrations following a
      single oral administration of each reference drug to healthy volunteers were
      simulated, and the prediction accuracy for human PK was compared between
      empirical approaches and the optimized PBPK model. In the drugs with low species
      specific CLtot, there was little difference in predictability for maximum
      concentration (Cmax), time to maximum plasma concentration (Tmax), and area under
      the curve (AUC) (absolute average fold error: 1.3-2.4). In contrast, the
      optimized PBPK model predicted Cmax and AUC of the drugs with high species
      specific CLtot with lower absolute average fold error (Cmax and AUC: 2.8 and 3.2,
      respectively) than those of the empirical approach (Cmax and AUC: 2.6-4.9 and 3.9
      10.7, respectively). Therefore, the optimized PBPK model is useful for human PK
      prediction of drugs with species-specific CLtot.

PMID- 29331383
TI  - Population Pharmacokinetics of High-Dose Methotrexate in Patients With Primary
      Central Nervous System Lymphoma.
AB  - The intra- and inter-individual variances of methotrexate (MTX) pharmacokinetics
      are extremely large, and the pharmacokinetic property of MTX in patients with
      primary central nervous system lymphoma (PCNSL) is unestablished. A total of 701
      MTX plasma concentrations from 98 patients with PCNSL under high-dose MTX therapy
      were used to develop the population pharmacokinetic (popPK) model of MTX by using
      the nonlinear mixed-effects modeling method. A 2-compartment model was employed
      to describe the pharmacokinetic property of MTX. In the final popPK model,
      inclusion of serum creatinine and body surface area significantly reduced
      objective function value for clearance over the base model (p <0.001), and
      inclusion of age significantly reduced objective function value for distribution
      volume of central compartment (Vc) over the base model (p <0.001). In the final
      popPK model, the inter-individual clearance = 6.67 * (SCR/68.1)-0.48 *
      (BSA/1.75)1.17; Vc = 24.46 * (age/57.16)0.81. The precision of all parameters was
      acceptable (relative standard error <28.61%). Bootstrap and visual predictive
      check results indicated that the final popPK model was stable with acceptable
      predictive ability. The popPK model may be useful for personalized medication in
      PCNSL patients under high-dose MTX therapy. Further studies are warranted to
      confirm the results.

PMID- 29331384
TI  - Evaluative feedback delivery and the factors that affect success.
AB  - This study examines the factors that can affect the credibility, influence, and
      utility of evaluative feedback. These factors include the delivery strategy,
      accuracy, and type (positive/negative) of feedback provided. In this study over
      500 participants were asked to complete a task, and were then randomly assigned
      to different conditions with varied feedback delivery methods, feedback accuracy,
      and types of feedback (positive/negative). Then they were asked questions about
      the feedback's credibility, influence, and utility.

PMID- 29331387
TI  - Tumor associated macrophages and angiogenesis dual-recognizable nanoparticles for
      enhanced cancer chemotherapy.
AB  - Tumor-associated macrophages (TAMs) and angiogenesis are increasingly considered
      as the pivotal factors that affect tumor progress. Herein, we developed the
      paclitaxel (PTX)-loaded nanoparticles (NP/PTX) and decorated it with an
      innovative peptide YI (YINP/PTX) for simultaneously targeting delivery of drug to
      TAMs and angiogenesis. We demonstrated that the modification of YI peptide
      significantly enhanced the internalization of nanoparticles by cells and
      accumulation of nanoparticles in tumor tissues, but down regulated the
      distribution of them in normal tissues especially the liver. We also made a
      confirmation that the YI peptide decorated nanoparticles had an excellent co
      localization with TAMs and angiogenesis in vivo. Finally, in the HT-26 colorectal
      tumor-bearing mice, a pharmacodynamic evaluation was performed and results showed
      that the YINP/PTX was more effective than other PTX formulations in anti-tumor
      growth. These results together suggested that the prepared nanoparticles are
      promising in targeting delivery of chemotherapeutics to tumor microenvironment
      for enhancing tumor therapy effect.

PMID- 29331385
TI  - Guidelines of care for the management of basal cell carcinoma.
AB  - Basal cell carcinoma (BCC) is the most common form of human cancer, with a
      continually increasing annual incidence in the United States. When diagnosed
      early, the majority of BCCs are readily treated with office-based therapy, which
      is highly curative. In these evidence-based guidelines of care, we provide
      recommendations for the management of patients with BCC, as well as an in-depth
      review of the best available literature in support of these recommendations. We
      discuss biopsy techniques for a clinically suspicious lesion and offer
      recommendations for the histopathologic interpretation of BCC. In the absence of
      a formal staging system, the best available stratification based on risk for
      recurrence is reviewed. With regard to treatment, we provide recommendations on
      treatment modalities along a broad therapeutic spectrum, ranging from topical
      agents and superficially destructive modalities to surgical techniques and
      systemic therapy. Finally, we review the available literature and provide
      recommendations on prevention and the most appropriate follow-up for patients in
      whom BCC has been diagnosed.

PMID- 29331386
TI  - Guidelines of care for the management of cutaneous squamous cell carcinoma.
AB  - Cutaneous squamous cell carcinoma (cSCC) is the second most common form of human
      cancer and has an increasing annual incidence. Although most cSCC is cured with
      office-based therapy, advanced cSCC poses a significant risk for morbidity,
      impact on quality of life, and death. This document provides evidence-based
      recommendations for the management of patients with cSCC. Topics addressed
      include biopsy techniques and histopathologic assessment, tumor staging, surgical
      and nonsurgical management, follow-up and prevention of recurrence, and
      management of advanced disease. The primary focus of these recommendations is on
      evaluation and management of primary cSCC and localized disease, but where
      relevant, applicability to recurrent cSCC is noted, as is general information on
      the management of patients with metastatic disease.

PMID- 29331388
TI  - E4BP4 inhibits AngII-induced apoptosis in H9c2 cardiomyoblasts by activating the
      PI3K-Akt pathway and promoting calcium uptake.
AB  - The bZIP transcription factor E4BP4 is a survival factor that is known to be
      elevated in diseased heart and promote cell survival. In this study the role of
      E4BP4 on angiotensin-II (AngII)-induced apoptosis has been examined in in vitro
      cell model. H9c2 cardiomyoblast cells that overexpressed E4BP4 were exposed to
      AngII to observe the cardio-protective effects of E4BP4 on hypertension related
      apoptosis. The results from TUNEL assays revealed that E4BP4 significantly
      attenuated AngII-induced apoptosis. Further analysis by Western blot and RT-PCR
      showed that E4BP4 inhibited AngII-induced IGF-II mRNA expression and cleavage of
      caspase-3 through the PI3K-Akt pathway. In addition, E4BP4 enhanced calcium
      reuptake into the sacroplasmic reticulum by down-regulating PP2A and by up
      regulating the phosphorylation of PKA and PLB proteins. Our findings indicate
      that E4BP4 functions as a survival factor in cardiomyoblasts by inhibiting IGF-II
      transcription and by regulating calcium cycling.

PMID- 29331389
TI  - Capn4 promotes colorectal cancer cell proliferation by increasing MAPK7 through
      activation of the Wnt/beta-Catenin pathway.
AB  - Increasing evidence has suggested that Capn4 is upregulated and functions as a
      potential tumor promoter in several human cancer types. However, the potential
      biological roles and regulatory mechanisms of Capn4 in colorectal cancer (CRC)
      remains unclear. Here, we found that Capn4 expression was elevated in CRC tissues
      than adjacent noncancerous tissues. Additionally, we also found that
      overexpression of Capn4 is significantly correlated with tumor progression and
      poor survival in CRC patients. Furthermore, our experimental data revealed that
      increased expression of Capn4 was observed in CRC cell lines and ectopic
      expression of Capn4 significantly enhanced in vitro cell proliferation, whereas
      knockdown of Capn4 suppressed CRC cells growth in vitro and in vivo. Moreover,
      our results indicate that Capn4 promotes cell proliferation by increasing MAPK7
      expression, which has been reported to control the proliferation of many cancers.
      Mechanistically, Capn4 upregulates MAPK7 expression through activation of the
      Wnt/beta-Catenin pathway in CRC cells. Therefore, we identified a tumorigenic
      role of Capn4 in CRC and suggested a potential therapeutic target for CRC
      patients.

PMID- 29331390
TI  - The TET2/E-cadherin/beta-catenin regulatory loop confers growth and invasion in
      hepatocellular carcinoma cells.
AB  - The poor outcome of hepatocellular carcinoma (HCC) is mainly due to the
      development of fast growth, invasion and metastasis. The role of TET2 has been
      implicated in some cancer types, but its role and mechanisms in HCC remains
      elusive. In this study, our findings indicated that TET2 expression frequently
      increased in HCC and that TET2 expressional upregulation correlated with HCC
      progression. TET2 knockdown inhibited HCC cells proliferation in vitro and growth
      in vivo, and inhibited the invasion potential of HCC cells. Mechanically, TET2
      knockdown upregulated E-cadherin expression and then attenuated beta-catenin
      transactivation in HCC cells. TET2 repressed E-cadherin expression via recruited
      HDAC1 to E-cadherin promoter to reduce the H3K9Ac and H4K16Ac levels. Moreover,
      beta-catenin signaling transcriptionally regulated TET2 expression to form a
      positive feedback in HCC cells. These findings indicate that the dysregulation of
      TET2/E-cadherin/beta-catenin regulatory loop is a critical oncogenic event in HCC
      progression.

PMID- 29331391
TI  - microRNA-mediated regulation of splicing factors SRSF1, SRSF2 and hnRNP A1 in
      context of their alternatively spliced 3'UTRs.
AB  - SRSF1, SRSF2 and hnRNP A1 are splicing factors that regulate the expression of
      oncogenes and tumor suppressors. SRSF1 and SRSF2 contribute to the carcinogenesis
      in the kidney. Despite their importance, the mechanisms regulating their
      expression in cancer are not entirely understood. Here, we investigated the
      microRNA-mediated regulation of SRSF1, SRSF2 and hnRNP A1 in renal cancer. The
      expression of microRNAs predicted to target SRSF1, SRSF2 and hnRNP A1 was
      disturbed in renal tumors compared with controls. Using qPCR, Western blot/ICC
      and luciferase reporter system assays we identified microRNAs that contribute to
      the regulation of expression of SRSF1 (miR-10b-5p, miR-203a-3p), SRSF2 (miR-183
      5p, miR-200c-3p), and hnRNP A1 (miR-135a-5p, miR-149-5p). Silencing of SRSF1 and
      SRSF2 enhanced the expression of their targeting microRNAs. miR-183-5p and miR
      200c-3p affected the expression of SRSF2-target genes, TNFRSF1B, TNFRSF9, CRADD
      and TP53. 3'UTR variants of SRSF1 and SRSF2 differed by the presence of miRNA
      binding sites. In conclusion, we identified a group of microRNAs that contribute
      to the regulation of expression of SRSF1, SRSF2 and hnRNP A1. The microRNAs
      targeting SRSF1 and SRSF2 are involved in a regulatory feedback loop. microRNAs
      miR-183-5p and miR-200c-3p that target SRSF2, affect the expression of genes
      involved in apoptotic regulation.

PMID- 29331392
TI  - What gynaecologists need to master: Consensus on medical expertise outcome of pan
      European postgraduate training in obstetrics and gynecology.

PMID- 29331395
TI  - Tyrosine hydroxylase as a sentinel for central and peripheral tissue responses in
      Parkinson's progression: Evidence from clinical studies and neurotoxin models.
AB  - Parkinson's disease (PD) is a common neurodegenerative disease worldwide. While
      the typical motor symptoms of PD are well known, the lesser known non-motor
      symptoms can also greatly impact the patient's quality of life. These symptoms
      often appear before motor impairment, therefore identifying biomarkers that may
      predict PD risk or pathology has been a major and challenging endeavour. Given
      that the loss of dopamine, and its rate-limiting enzyme tyrosine hydroxylase (TH)
      occurs in PD, the expression and accompanying post-translational changes in TH
      during PD progression could yield insight into the disruption of cellular
      signalling occurring in the CNS, and also in peripheral tissues wherein
      catecholamine function plays a role. Furthermore, changes in expression and
      phosphorylation of TH in the brain and periphery can potentially reveal how TH
      stability and function are compromised in PD. As such, these changes can reveal
      how catecholamine synthesis capacity is gradually compromised and how changes in
      cellular signalling may govern the functional status of remaining
      catecholaminergic neurons. This review summarises the findings of clinical PD and
      neurotoxin models of PD that assessed TH expression or phosphorylation in
      catecholaminergic pathways in the brain and relevant peripheral tissues. We
      propose that establishing similar changes in TH expression and function in the
      CNS and periphery of established neurotoxin models can be a potential reference
      for comparison to changes in TH in human peripheral tissues. These changes in TH
      expression and phosphorylation may have predictive validity to estimate risk of
      PD progression before motor impairment is evident.

PMID- 29331393
TI  - Oral health considerations for pediatric patients with sickle cell disease.

PMID- 29331396
TI  - Autophagy in ischemic stroke.
AB  - Autophagy is a self-eating cellular catabolic pathway, through which long-lived
      proteins, damaged organelles and misfolded proteins are degraded and recycled for
      the maintenance of cellular homeostasis and normal cellular functions. Autophagy
      plays an important homeostatic role in the regulation of cell survival.
      Accumulating evidence shows that autophagy is activated in various cell types in
      the brain such as neurons, glia cells, and brain microvascular cells upon
      ischemic stroke. However, the exact role and molecular mechanisms of autophagy
      process that is implicated in ischemic stroke have yet to be elucidated. This
      review aims to provide a comprehensive view of the regulation of autophagy in
      neurons, glia cells, and brain microvascular cells in response to ischemia
      stress. We also review the recent advance on the understanding of the involvement
      of autophagy in the pathological process during cerebral ischemic
      preconditioning, perconditioning and postconditioning. We propose a crosstalk
      between autophagy, necroptosis, and apoptosis that contribute to ischemic stroke.
      In addition, we discuss the interactions between autophagy and oxidative stress,
      mitochondrial dysfunction and endoplasmic reticulum stress.

PMID- 29331397
TI  - Persistent hyperparathyroidism as a risk factor for long-term graft failure: the
      need to discuss indication for parathyroidectomy.
AB  - BACKGROUND: Although a successful kidney transplant (KTx) improves most of the
      mineral and bone disorders (MBD) produced by chronic kidney disease (CKD),
      hyperparathyroidism may persist (pHPT). Current guidelines recommend
      parathyroidectomy if serum parathormone is persistently elevated 1 year after
      KTx, because pHPT has been recently associated with poor graft outcomes. However,
      whether patients with pHPT and adequate renal function are at risk for long-term
      graft failure is unknown. METHODS: Longitudinal follow-up of 911 adults submitted
      to KTx between January 2005 and December 2014, with estimated glomerular
      filtration rate (eGFR) >= 30 mL/min 1 year after surgery. Clinical and laboratory
      data were collected from electronic database. Graft failure was defined as return
      to dialysis. RESULTS: Overall, 62% of the patients were classified as having pHPT
      1 year after KTx. After a mean follow-up time of 47 months, there were 59 graft
      failures (49 in pHPT and 10 in non-pHPT group, P = .003). At last follow-up,
      death-censored graft survival was lower in the pHPT group (P = .009), even after
      adjustment for age at KTx, donor age, donor type, acute rejection,
      parathyroidectomy, and eGFR at 1 year after transplantation (odds ratio [OR]
      1.99; 1.004-3.971; P = .049). A PTH of 150 pg/mL at 6 months was the best cutoff
      to predict pHPT at 1 year (specificity = 92.1%). CONCLUSION: Having pHPT after a
      successful KTx increases the long-term risk of death-censored graft failure. This
      result highlights the need for better recognition and management of CKD-MBD
      before and during the first year after KTx, and opens a discussion on the more
      appropriate timing to perform parathyroidectomy.

PMID- 29331399
TI  - Discussion.

PMID- 29331398
TI  - Critical differences between elective and emergency surgery: identifying domains
      for quality improvement in emergency general surgery.
AB  - OBJECTIVE: The objective of our study was to characterize providers' impressions
      of factors contributing to disproportionate rates of morbidity and mortality in
      emergency general surgery to identify targets for care quality improvement.
      BACKGROUND: Emergency general surgery is characterized by a high-cost burden and
      disproportionate morbidity and mortality. Factors contributing to these observed
      disparities are not comprehensively understood and targets for quality
      improvement have not been formally developed. METHODS: Using a grounded theory
      approach, emergency general surgery providers were recruited through purposive
      criterion-based sampling to participate in semi-structured interviews and focus
      groups. Participants were asked to identify contributors to emergency general
      surgery outcomes, to define effective care for EGS patients, and to describe
      operating room team structure. Interviews were performed to thematic saturation.
      Transcripts were iteratively coded and analyzed within and across cases to
      identify emergent themes. Member checking was performed to establish credibility
      of the findings. RESULTS: A total of 40 participants from 5 academic hospitals
      participated in either individual interviews (n = 25 [9 anesthesia, 12 surgery, 4
      nursing]) or focus groups (n = 2 [15 nursing]). Emergency general surgery was
      characterized by an exceptionally high level of variability, which can be
      subcategorized as patient-variability (acute physiology and comorbidities) and
      system-variability (operating room resources and workforce). Multidisciplinary
      communication is identified as a modifier to variability in emergency general
      surgery; however, nursing is often left out of early communication exchanges.
      CONCLUSION: Critical variability in emergency general surgery may impact
      outcomes. Patient-variability and system-variability, with focus on
      multidisciplinary communication, represent potential domains for quality
      improvement in this field.

PMID- 29331400
TI  - Locally advanced pancreas cancer: Staging and goals of therapy.
AB  - BACKGROUND: Patients with locally advanced pancreatic cancer have historically
      been considered inoperable. The purpose of this report was to determine
      resectability rates for patients with locally advanced pancreatic cancer based on
      our recently described definitions of type A and type B locally advanced
      pancreatic cancer. METHODS: An institutional prospective pancreas cancer database
      was queried for consecutive patients with locally advanced pancreatic cancer
      treated between January 2009 and June 2017. All pretreatment imaging was re
      reviewed and patients were categorized as locally advanced pancreatic cancer type
      A or type B. Demographics, induction therapy, resection type, and outcomes were
      reviewed. RESULTS: We identified 108 consecutive patients; 12 were excluded from
      analysis due to the absence of available pretreatment imaging or they had not yet
      completed all intended neoadjuvant therapy. Of the remaining 96 patients (45 type
      A, 51 type B), disease progression occurred in 19 (20%) during induction therapy
      and 30 (31%) were deemed inoperable at final preoperative restaging. Therefore,
      47 (49%) of 96 patients were taken to surgery and 40 (42%) underwent successful
      resection (28 [62%] of 45 type A and 12 [24%] of 51 type B); an RO resection was
      achieved in 32 (80%). Metastatic disease was found intraoperatively (6 at
      laparoscopy, 1 at laparotomy) in 7 (15%) of 47 patients. There were no
      mortalities; 6 (15%) patients experienced major postoperative complications.
      Resected patients had a median overall survival of 38.9 months. CONCLUSION:
      Locally advanced pancreatic cancer can be dichotomized into type A and B with
      distinctly different probabilities of completing all therapy to include surgery;
      thereby allowing goals of therapy to be established at the time of diagnosis.
      Multimodality therapy that includes surgery can be accomplished in selected
      patients with locally advanced pancreatic cancer and is associated with a median
      overall survival that approximates earlier stages of disease. (Surgery
      2017;160:XXX-XXX.).

PMID- 29331401
TI  - Preoperative dipstick albuminuria and other urine abnormalities predict acute
      kidney injury and patient outcomes.
AB  - BACKGROUND: It is unclear whether pathologic findings on preoperative urinalysis
      are associated with the risk of postoperative acute kidney injury (AKI).
      Therefore, we performed a retrospective review to investigate this association.
      METHODS: We assessed the clinical significance of preoperative dipstick
      urinalysis in a 10-year surgery cohort from a tertiary hospital in Korea.
      Patients without available information on perioperative serum creatinine levels
      or kidney injury prior to surgery were excluded. Preoperative dipstick urinalysis
      parameters, including albuminuria, hematuria, pyuria, and others were studied.
      The primary outcome was postoperative acute kidney injury. Secondary outcomes
      were postoperative 1-year mortality and progression of poor kidney function
      parameters. RESULTS: We enrolled 40,090 patients. The presence of dipstick
      albuminuria was associated with an increased risk of postoperative AKI (adjusted
      odds ratio 1.47 [1.29-1.66], P < .001), and the association showed a dose
      response relationship. High specific gravity was significantly associated with
      increased risk of AKI (adjusted odds ratio 1.30 [1.04-1.63], P = .02).
      Furthermore, in patients with postoperative AKI, those with baseline albuminuria
      had a worse prognosis with regard to 1-year mortality (adjusted hazard ratio 2.81
      [1.56-5.09], P < .001) and persistent renal function impairment (adjusted odds
      ratio 2.07 [1.21-3.46], P = .007), independent of estimated glomerular filtration
      rate values. Patients with baseline hematuria and pyuria also had an inferior
      postoperative AKI prognosis when compared to those without the urinalysis
      abnormalities. CONCLUSION: Baseline dipstick urinalysis may predict postoperative
      AKI and may be significantly associated with prognosis after surgery. (Surgery
      2017;160:XXX-XXX.).

PMID- 29331402
TI  - Tailored surgical treatment of duodenal polyposis in familial adenomatous
      polyposis syndrome.
AB  - BACKGROUND: To review our experience in patients undergoing operative treatment
      for duodenal polypoisis associated with familial adenomatous polyposis with an
      emphasis on operative approach and long-term outcomes. METHODS: Duodenal
      polypoisis associated with familial adenomatous polyposis patients undergoing
      operative treatment were studied retrospectively excluding patients with
      preoperative duodenal cancer. RESULTS: Of 767 patients in the database, 63 (8.2%)
      patients underwent operative treatment: 42 (67%) pancreas-sparing duodenectomy,
      15 (24%) pancreatoduodenectomy, and 6 (9.5%) segmental duodenal resection; the
      majority for Spigelman stages III and IV polyposis. Overall 9.6% had
      adenocarcinoma postoperatively (28.6% in the pancreatoduodenectomy group; P =
      .01). The proportion of Spigelman stages III and IV with cancer were 9.5% and
      6.5%, respectively. Pathologic upgrade to cancer in patients with low grade
      dysplasia and high-grade dysplasia on preoperative biopsy was 5.7% and 6.7%,
      respectively (P = .13). At a median follow-up of 16 years, 7.7% needed a second
      duodenal polypoisis associated with familial adenomatous polyposis-related
      operation. Progression to high grade dysplasia or cancer in the stomach occurred
      in 15.4% of patients. Median overall survival and recurrence-free survival was at
      least 16 years and 15.6 years. No significant group-based differences were noted
      on follow-up. CONCLUSION: The majority of patients with duodenal polypoisis
      associated with familial adenomatous polyposis can achieve long-term, cancer-free
      survival with organ-preserving approaches (pancreas-sparing-duodenectomy and
      segmental-duodenal-resection) with survival not dependent on the type of
      resection.

PMID- 29331403
TI  - Anatomy of change: a Kodak moment.

PMID- 29331404
TI  - Reliability and validity of the adapted Resistance Training Skills Battery for
      Children.
AB  - OBJECTIVES: Resistance training (RT) is emerging as a training modality to
      improve motor function and facilitate physical activity participation in children
      across the motor proficiency spectrum. Although RT competency assessments have
      been established and validated among adolescent cohorts, the extent to which
      these methods are suitable for assessing children's RT skills is unknown. This
      project aimed to assess the psychometric properties of the adapted Resistance
      Training Skills Battery for Children (RTSBc), in children with varying motor
      proficiency. DESIGN: Repeated measures design with 40 participants (M age=8.2+/
      1.7years) displaying varying levels of motor proficiency. METHODS: Participants
      performed the adapted RTSBc on two occasions, receiving a score for their
      execution of each component, in addition to an overall RT skill quotient child
      (RTSQc). Cronbach's alpha, intra-class correlation (ICC), Bland-Altman analysis,
      and typical error were used to assess test-retest reliability. To examine
      construct validity, exploratory factor analysis was performed alongside computing
      correlations between participants' muscle strength, motor proficiency, age, lean
      muscle mass, and RTSQc. RESULTS: The RTSBc displayed an acceptable level of
      internal consistency (alpha=0.86) and test-retest reliability (ICC range=0.86
      0.99). Exploratory factor analysis supported internal test structure, with all
      six RT skills loading strongly on a single factor (range 0.56-0.89). Analyses of
      structural validity revealed positive correlations for RTSQc in relation to motor
      proficiency (r=0.52, p<0.001) and strength scores (r=0.61, p<0.001). CONCLUSIONS:
      Analyses revealed support for the construct validity and test-retest reliability
      of the RTSBc, providing preliminary evidence that the RTSBc is appropriate for
      use in the assessment of children's RT competency.

PMID- 29331405
TI  - Reliability and Validity of the Turkish Version of the Consensus Auditory
      Perceptual Evaluation of Voice (CAPE-V).
AB  - OBJECTIVES: The main purpose of this study was to culturally adapt the Consensus
      Auditory-Perceptual Evaluation of Voice (CAPE-V) to Turkish and to evaluate its
      internal consistency, validity, and reliability. MATERIALS AND METHODS: The
      Turkish version of CAPE-V was developed, and with the use of a prospective case
      control design, the voice recordings of 130 participants were collected according
      to CAPE-V protocol. Auditory-perceptual evaluation was conducted according to
      CAPE-V and Grade, Roughness, Breathiness, Asthenia, and Strain (GRBAS) scale by
      two ear, nose, and throat specialists and two speech and language therapists. The
      different types of voice disorders, classified as organic and functional
      disorders, were compared in terms of their CAPE-V scores. RESULTS: The overall
      severity parameter had the highest intrarater and inter-reliability values for
      all the participants. For all four raters, the differences in the six CAPE-V
      parameters between the study and the control groups were found to be
      statistically significant. Among the correlations for the comparable parameters
      of the CAPE-V and the GRBAS scales, the highest correlation was found between the
      overall severity-grade parameters. There was no difference found between the
      organic and functional voice disorders in terms of the CAPE-V scores.
      CONCLUSIONS: The Turkish version of CAPE-V has been proven to be a reliable and
      valid instrument to use in the auditory-perceptual evaluation of voice. For the
      future application of this study, it would be important to investigate whether
      cepstral measures correlate with the auditory-perceptual judgments of dysphonia
      severity collected by a Turkish version of the CAPE-V.

PMID- 29331406
TI  - Effect of Auditory-Perceptual Training With Natural Voice Anchors on Vocal
      Quality Evaluation.
AB  - PURPOSE: To analyze the effects of auditory-perceptual training with anchor
      stimuli of natural voices on inter-rater agreement during the assessment of vocal
      quality. STUDY DESIGN: This is a quantitative nature study. METHODS: An auditory
      perceptual training site was developed consisting of Programming Interface A, an
      auditory training activity, and Programming Interface B, a control activity. Each
      interface had three stages: pre-training/pre-interval evaluation,
      training/interval, and post-training/post-interval evaluation. Two experienced
      evaluators classified 381 voices according to the GRBASI scale (G-grade, R
      roughness, B-breathiness, A-asthenia, S-strain, I-instability). Voices were
      selected that received the same evaluation by both evaluators: 57 voices for
      evaluation and 56 for training were selected, with varying degrees of deviation
      across parameters. Fifteen inexperienced evaluators were then selected. In the
      pre-, post-training, pre-, and postinterval stages, evaluators listened to the
      voices and classified them via the GRBASI scale. In the stage interval evaluators
      read a text. In the stage training each parameter was trained separately.
      Evaluators analyzed the degrees of deviation of the GRBASI parameters based on
      anchor stimuli, and could only advance after correctly classifying the voices. To
      quantify inter-rater agreement and provide statistical analyses, the AC1
      coefficient, confidence intervals, and percentage variation of agreement were
      employed. RESULTS: Except for the asthenia parameter, decreased agreement was
      observed in the control condition. Improved agreement was observed with auditory
      training, but this improvement did not achieve statistical significance.
      CONCLUSION: Training with natural voice anchors suggest an increased inter-rater
      agreement during perceptual voice analysis, potentially indicating that new
      internal references were established.

PMID- 29331407
TI  - Decreased health-related quality of life in children and adolescents with
      autoimmune hepatitis.
AB  - OBJECTIVE: The objective of this study was to evaluate the health-related quality
      of life in children and adolescents with autoimmune hepatitis. METHODS: A cross
      sectional assessment with the Pediatric Quality of Life Inventory 4.0 (PedsQL
      4.0) was completed for 80 patients with autoimmune hepatitis and 45 healthy
      controls. Demographic data, prednisone dose, disease remission state, disease
      severity, and abdominal pain were also evaluated. RESULTS: Based on the child
      self-reports, physical, emotional, school, and total scores were significantly
      lower in autoimmune hepatitis patients when compared with controls (p<0.05).
      Based on the parental reports, only the physical and total scores were
      significantly lower in autoimmune hepatitis patients versus controls (p<0.05).
      Further analysis in autoimmune hepatitis patients with abdominal pain in the last
      month revealed significantly lower physical, social, and total median scores
      (p<0.05). No differences were observed based on disease remission state or
      disease severity (p>0.05). Autoimmune hepatitis patients who received a
      prednisone dose below 0.16mg/kg/day at the time of the interview showed
      significantly higher physical scores than those who received a dose similar to or
      above 0.16mg/kg/day (87.5 [50-100] vs. 75 [15.63-100], p=0.006). CONCLUSIONS:
      Reduced scores in the physical, emotional, and school domains were observed in
      pediatric autoimmune hepatitis patients compared to control patients. Abdominal
      pain and corticosteroid dose negatively influenced the health-related quality of
      life in children and adolescents with autoimmune hepatitis.

PMID- 29331408
TI  - Long-term craniofacial morphology in young adults treated for a non-syndromal
      UCLP: A systematic review.
AB  - Minimizing mid-facial growth impairment is one of the treatment goals in cleft
      lip and palate surgery. As growth of the maxilla extends into young adulthood,
      long-term evaluation is essential to make a comprehensive assessment of a
      treatment protocol. There are numerous treatment approaches for cleft lip/palate
      surgery, and most have the characteristic distinction between either an early or
      a late cleft palate closure. PRISMA guidelines were applied to explore the
      quality of the current literature and to identify treatment factors influencing
      long-term cephalometric outcomes. The literature search was conducted in Pubmed,
      The Cochrane Library and Embase. We included studies evaluating cephalometric
      outcomes (SNA and ANB values on 2D cephalograms) in UCLP patients with a mean age
      of 16 years and older. Studies with an inadequate description of the timing of
      surgery were excluded. 17 studies comprising 906 patients were selected and
      included for critical appraisal. Treatment protocols differed considerably among
      the included studies and inconsistent methodology was common. Eight studies
      applied a one-stage procedure, 11 studies performed a two-stage reconstruction,
      and five studies made use of a vomer flap. Applying a multivariate model, we did
      not identify any treatment factors that significantly influenced growth (SNA/ANB
      values), except for the method of inclusion, suggesting the presence of
      significant selection bias within the studies. The current literature remains
      inadequate for evidence-based decision making and to advise parents if an early
      or late palate closure leads to a more favorable maxillary outgrowth. This
      manuscript will propose guidelines and recommended quality criteria for future
      studies.

PMID- 29331409
TI  - Spreader graft placement: Location, location, location.

PMID- 29331410
TI  - Implementing CRISPR-Cas technologies in conventional and non-conventional yeasts:
      Current state and future prospects.
AB  - Within five years, the CRISPR-Cas system has emerged as the dominating tool for
      genome engineering, while also changing the speed and efficiency of metabolic
      engineering in conventional (Saccharomyces cerevisiae and Schizosaccharomyces
      pombe) and non-conventional (Yarrowia lipolytica, Pichia pastoris syn.
      Komagataella phaffii, Kluyveromyces lactis, Candida albicans and C. glabrata)
      yeasts. Especially in S. cerevisiae, an extensive toolbox of advanced CRISPR
      related applications has been established, including crisprTFs and gene drives.
      The comparison of innovative CRISPR-Cas expression strategies in yeasts presented
      here may also serve as guideline to implement and refine CRISPR-Cas systems for
      highly efficient genome editing in other eukaryotic organisms.

PMID- 29331411
TI  - Tailoring cyanobacterial cell factory for improved industrial properties.
AB  - Photosynthetic biomanufacturing provides a promising solution for sustainable
      production of biofuels and biochemicals. Cyanobacteria are among the most
      promising microbial platforms for the construction of photosynthetic cell
      factories. Metabolic engineering of cyanobacteria has enabled effective
      photosynthetic synthesis of diverse natural or non-natural metabolites, while
      commercialization of photosynthetic biomanufacturing is usually restricted by
      process and economic feasibilities. In actual outdoor conditions, active cell
      growth and product synthesis is restricted to narrow light exposure windows of
      the day-night cycles and is threatened by diverse physical, chemical, and
      biological environmental stresses. For biomass harvesting and bioproduct
      recovery, energy and cost consuming processing and equipment is required, which
      further decreases the economic and environmental competitiveness of the entire
      process. To facilitate scaled photosynthetic biomanufacturing, lots of efforts
      have been made to engineer cyanobacterial cell properties required by robust &
      continual cultivation and convenient & efficient recovery. In this review, we
      specifically summarized recently reported engineering strategies on optimizing
      industrial properties of cyanobacterial cells. Through systematically re-editing
      the metabolism, morphology, mutualism interaction of cyanobacterial chassis
      cells, the adaptabilities and compatibilities of the cyanobacterial cell
      factories to the industrial process could be significantly improved. Cell growth
      and product synthesis of the tailored cyanobacterial cells could be expanded and
      maintained at night and in stressful environments, while convenient biomass
      harvesting could also be expected. For developing more feasible cyanobacterial
      photosynthetic biomanufacturing in large scale, we here propose the importance of
      tailoring industrial properties of cyanobacteria and outline the directions that
      should be exploited in the future.

PMID- 29331412
TI  - Anti-leukemic effects of PPARgamma ligands.
AB  - The peroxisome proliferator-activated receptor (PPAR) gamma, a subtype of PPARs,
      is a member of the nuclear receptor family. PPARgamma and its ligands contribute
      to various types of diseases including cancer. Given that currently developed
      therapies against leukemia are not very effective or safe, PPARgamma ligands have
      been shown to be a new class of compounds with the potential to treat hematologic
      malignancies, particularly leukemia. The capability of PPARgamma ligands to
      induce apoptosis, inhibit proliferation, and promote differentiation of leukemia
      cells suggests it has significant potential as a drug against leukemia. However,
      the specific mechanisms and molecules involved are not well-understood, although
      a number of PPARgamma ligands with anti-leukemic effects have been identified.
      This may explain why PPARgamma ligands have not been widely evaluated in clinical
      trials. To fill the gaps in the lack of understanding of specific anti-leukemic
      processes of PPARgamma ligands and further adapt these molecules as anti-leukemic
      agents, this review describes previous studies of the anti-leukemic effects of
      PPARgamma ligands.

PMID- 29331413
TI  - eEF-2 Kinase-targeted miR-449b confers radiation sensitivity to cancer cells.
AB  - The roles of microRNA in regulation of various biological processes and in
      modulation of therapeutic effects have been widely appreciated. In this study, we
      found a positive correlation between miR-449 b expression and radiation
      sensitivity in cancer cells and in tumor specimens from patients. We showed that
      eEF-2 kinase, a negative regulator of global protein synthesis, is a target of
      miR-449 b. Introducing a miR-449 b mimic into cancer cells led to suppression of
      eEF-2 kinase expression, leading to increases of protein synthesis and depletion
      of cellular ATP. Further, we demonstrated that the miR-449 b mimic rendered the
      cancer cells more sensitive to ionizing radiation both in vitro (cell culture)
      and in vivo (animal xenograft model). Moreover, the radiation sensitivity
      conferred by miR-449 b could be blunted by cycloheximide, an inhibitor of protein
      synthesis, or by direct delivery of ATP liposome, supporting eEF-2 kinase as a
      mediator of the radio-sensitizing effects of miR-449 b. These results indicate
      that miR-449 b, which is frequently down-regulated in radio-resistant cancers,
      may represent a new critical determinant of radio-sensitivity.

PMID- 29331415
TI  - Nogo-B receptor promotes epithelial-mesenchymal transition in non-small cell lung
      cancer cells through the Ras/ERK/Snail1 pathway.
AB  - Nogo-B receptor (NgBR) is a specific receptor of Nogo-B that regulates vascular
      remodeling and angiogenesis. Previously, we found that NgBR promotes the membrane
      translocation and activation of Ras in breast cancer cells and enhances the
      chemoresistance of hepatocellular carcinoma cells to 5-fluorouracil. However, the
      role of NgBR in lung cancer has not yet been elucidated. In the present study, we
      found that NgBR knockdown inhibited epithelial-mesenchymal transition (EMT) in
      non-small cell lung cancer (NSCLC) cells in vitro and metastasis of NSCLC cells
      in vivo. In contrast, NgBR overexpression promoted EMT in and lung metastasis of
      NSCLC cells. At the molecular level, NgBR modulated the expression of EMT-related
      proteins and enhanced the protein expression of Snail1, a crucial transcription
      factor that represses epithelial cell protein marker E-cadherin. Moreover, we
      found that NgBR overexpression promoted the membrane localization of Ras and
      activation of downstream MEK/ERK signaling pathway and that NgBR knockdown by
      using a specific shRNA inversely affected the expression of EMT-related proteins
      in NSCLC cells. Thus, our results provide novel insights on the regulatory role
      of NgBR in the metastasis of NSCLC that should be investigated further for
      developing a therapeutic strategy for treating patients with NSCLC.

PMID- 29331414
TI  - Inhibition of FASN and ERalpha signalling during hyperglycaemia-induced matrix
      specific EMT promotes breast cancer cell invasion via a caveolin-1-dependent
      mechanism.
AB  - Since disturbed metabolic conditions such as obesity and diabetes can be critical
      determinants of breast cancer progression and therapeutic failure, we aimed to
      determine the mechanism responsible for their pro-oncogenic effects. Using non
      invasive, epithelial-like ERalpha-positive MCF-7 and T47D human breast cancer
      cells we found that hyperglycaemia induced epithelial to mesenchymal transition
      (EMT), a key programme responsible for the development of metastatic disease.
      This was demonstrated by loss of the epithelial marker E-cadherin together with
      increases in mesenchymal markers such as vimentin, fibronectin and the
      transcription factor SLUG, together with an enhancement of cell growth and
      invasion. These phenotypic changes were only observed with cells grown on
      fibronectin and not with those plated on collagen. Analyzing metabolic
      parameters, we found that hyperglycaemia-induced, matrix-specific EMT promoted
      the Warburg effect by upregulating glucose uptake, lactate release and specific
      glycolytic enzymes and transporters. We showed that silencing of fatty acid
      synthase (FASN) and the downstream ERalpha, which we showed previously to mediate
      hyperglycaemia-induced chemoresistance in these cells, resulted in suppression of
      cell growth: however, this also resulted in a dramatic enhancement of cell
      invasion and SLUG mRNA levels via a novel caveolin-1-dependent mechanism.

PMID- 29331416
TI  - Deubiquitinating enzyme PSMD14 promotes tumor metastasis through stabilizing
      SNAIL in human esophageal squamous cell carcinoma.
AB  - The epithelial-mesenchymal transition (EMT) transcription factor SNAIL is
      associated with distant metastasis and poor prognosis of esophageal squamous cell
      carcinoma (ESCC) patients. The proteolysis of SNAIL is mediated by the ubiquitin
      proteasome system. Several E3 ligases have been characterized to promote SNAIL
      ubiquitination and degradation. However, the reverse process - deubiquitination
      of SNAIL remains largely unknown. In this study, we performed a mass spectrometry
      to examine the interaction between SNAIL and deubiquitinating enzyme(s).
      Subsequently, the deubiquitinating enzyme PSMD14 was identified to target SNAIL
      for deubiquitination and stabilization. Furthermore, knockdown of PSMD14
      significantly blocks SNAIL-induced EMT and then suppresses tumor cell migration
      and invasion in vitro and tumor metastasis in vivo. In addition, the high
      expression level of PSMD14 predicts poor prognosis for esophageal cancer
      patients. These findings suggest PSMD14 as a bona fide deubiquitinating enzyme to
      regulate SNAIL at the post-translational level and provide a promising
      therapeutic strategy against tumor metastasis of esophageal cancer.

PMID- 29331417
TI  - Down-regulation of RIP3 potentiates cisplatin chemoresistance by triggering HSP90
      ERK pathway mediated DNA repair in esophageal squamous cell carcinoma.
AB  - Receptor interacting protein kinase 3 (RIP3) is a critical regulator of
      programmed necrotic cell death. Here, we observed that RIP3 was significantly
      down-regulated in esophageal cancer. And its remaining expression was associated
      with better response to chemotherapy and prolonged survival. Notably, re
      expression of kinase-dead RIP3 also restored cisplatin sensitivity, suggesting
      that some roles of RIP3 beyond necroptosis may be involved in cisplatin-based
      chemosensitivity. To investigate the mechanisms, a large-scale quantitative
      proteomics study was performed after cisplatin treatment in RIP3-knockdown cells.
      In total, approximately 7000 protein groups were confidently identified, with a
      false discovery rate of 0.21% at the protein level. Of these proteins, 685
      displayed RIP3-dependent changes in abundance. Bioinformatics analyses indicated
      that DNA repair pathway was stimulated after RIP3 depletion. Functional studies
      showed that deficient RIP3 upregulated FOSL1 and POLD1 through activation of the
      HSP90/CDC37 complex and ERK phosphorylation in multiple cell lines. Furthermore,
      via inhibition of the HSP90/CDC37 complex, ERK and FOSL1 reversed the cisplatin
      resistance phenotype. These results suggest that RIP3 regulates cisplatin
      sensitivity through both pronecrotic and non-necrotic functions. RIP3 may be a
      potential marker for predicting chemosensitivity.

PMID- 29331418
TI  - Non-coding RNAs in cancer stem cells.
AB  - Cancer stem cells (CSCs) have been shown to play a key role in tumor initiation,
      progression, metastasis, and therapy resistance. Despite their potential clinical
      importance, the mechanism of CSC regulation is not well understood. Recent
      evidence suggests that different types of non-coding RNAs (ncRNA), such as
      microRNA (miRNA) and long non-coding RNA (LncRNA), play a role in regulating CSC
      growth and replication by modulating transcription factors and downstream
      signaling pathways activated in CSCs. Here, we review the recent major findings
      about how they affect stem cell quality acquisition and maintenance in CSCs, as
      well as metastasis and therapy resistance. Drawing connections between such
      discoveries could be conducive to the development of novel ncRNA-based
      therapeutics that can selectively target CSCs and reduce rates of cancer
      recurrence.

PMID- 29331419
TI  - The therapeutic potential of human adipose-derived mesenchymal stem cells
      producing CXCL10 in a mouse melanoma lung metastasis model.
AB  - Interferon gamma-induced protein 10 kDa (IP-10) is a potent chemoattractant and
      has been suggested to enhance antitumor activity and mediate tumor regression
      through multiple mechanisms of action. Multiple lines of evidence have indicated
      that genetically-modified adult stem cells represent a potential source for cell
      based cancer therapy. In the current study, we assessed therapeutic potential of
      human adipose derived mesenchymal stem cells (hADSC) genetically-modified to
      express IP-10 for the treatment of lung metastasis in an immunocompetent mouse
      model of metastatic melanoma. A Piggybac vector encoding IP-10 was employed to
      transfect hADSC ex vivo. Expression and bioactivity of the transgenic protein
      from hADSCs expressing IP-10 were confirmed prior to in vivo studies. Our results
      indicated that hADSCs expressing IP-10 could inhibit the growth of B16F10
      melanoma cells and significantly prolonged survival. Immunohistochemistry
      analysis, TUNEL assay and western blot analysis indicated that hADSCs expressing
      IP-10 inhibited tumor cell growth, hindered tumor infiltration of Tregs,
      restricted angiogenesis and significantly prolonged survival. In conclusion, our
      results demonstrated that targeting metastatic tumor sites by hADSC expressing IP
      10 could reduce melanoma tumor growth and lung metastasis.

PMID- 29331420
TI  - Dacomitinib antagonizes multidrug resistance (MDR) in cancer cells by inhibiting
      the efflux activity of ABCB1 and ABCG2 transporters.
AB  - The development of multidrug resistance (MDR) to chemotherapy remains a major
      challenge in the treatment of cancer. Numerous mechanisms have been recognized
      that cause MDR, but one of the most important mechanisms is overexpression of
      adenosine triphosphate (ATP)-binding cassette (ABC) transporters, through which
      the efflux of various anticancer drugs against their concentration gradients is
      powered by ATP. In recent years, small molecular tyrosine kinase inhibitors
      (TKIs) have been developed for treatment in various human cancers overexpressing
      epidermal growth factor receptor (EGFR). At the same time, some TKIs have been
      shown to be capable of inhibiting ABC transporter-mediated MDR. Dacomitinib (PF
      00299804) is a second generation, irreversible TKI, which has shown positive
      anticancer activities in some preclinical and clinical trials. As many TKIs are
      substrates or inhibitors of ABC transporters, this study investigates whether
      dacomitinib could interact with ABC subfamily members that mediate MDR, including
      ABCB1 (P-gp), ABCG2 (BCRP) and ABCC1 (MRP1). The results showed that dacomitinib
      at 1.0 MUM significantly reversed drug resistance mediated by ABCB1 and ABCG2,
      but not ABCC1, doing so by antagonizing the drug efflux function in ABCB1- and
      ABCG2-overexpressing cell lines. The reversal effect on ABCB1-overexpressing
      cells is more potent than that on ABCG2-overexpressing cells. In addition,
      dacomitinib at reversal concentration affected neither the protein expression
      level nor the localization of ABCB1 and ABCG2. Therefore, the mechanisms of this
      modulating effect are likely to be the following: first, as an inhibitor of ABCB1
      or ABCG2 transporters, dacomitinib binds to drug-substrate site in transmembrane
      domains (TMD) stably in a noncompetitive manner; or second, dacomitinib inhibits
      ATPase activity and maintains the stability of TMD conformation in a
      concentration-dependent manner thereby inhibiting the drug efflux function of
      ABCB1 or ABCG2 transporter. This study provides a useful combinational
      therapeutic strategy with dacomitinib and substrates of ABCB1 and/or ABCG2
      transporters in ABCB1- or ABCG2-overexpressing cancers.

PMID- 29331421
TI  - Hyperglycaemia-induced miR-301a promotes cell proliferation by repressing p21 and
      Smad4 in prostate cancer.
AB  - Hyperglycaemia promotes the development of Prostate cancer (PCa). However, the
      roles of miRNAs in this disease process and the underlying mechanisms are largely
      unknown. In this study, we recruited 391 PCa patients in China and found that PCa
      patients with high level blood glucose (>=100 mg/dL) trended to have high Gleason
      score (GS >= 7). miRNA-301a levels were significantly higher in prostate cancer
      than that in normal prostate tissues. Hyperglycaemia or high glucose treatment
      induced miR-301a expression in prostate tissues or PCa cell lines. miR-301a
      suppressed the expression of p21 and Smad4, and subsequently promoted G1/S cell
      cycle transition and cell proliferation in vitro and xenograft growth in nude
      mice in vivo. Furthermore, knockdown of p21 and Smad4 mimicked the effects of miR
      301a overexpression. Restoration of p21 and smad4 could interrupt the effects of
      miR-301a overexpression. Importantly, inhibition of miR-301a severely blocked
      high glucose-induced PCa cell growth both in vitro and in vivo. These results
      revealed a novel molecular link between hyperglycaemia and PCa. The miR-301a
      plays an important role in the hyperglycaemia-associated cancer growth, and
      represents a novel therapeutic target for PCa.

PMID- 29331422
TI  - FePt-Cys nanoparticles induce ROS-dependent cell toxicity, and enhance chemo
      radiation sensitivity of NSCLC cells in vivo and in vitro.
AB  - FePt-Cys nanoparticles (FePt-Cys NPs) have been well used in many fields, despite
      their poor solubility and stability. We synthetized a cysteine surface modified
      FePt NPs, which exhibited good solubility, stability and biocompatibility. We
      explored the insight mechanisms of the antitumor effects of this new nanoparticle
      system in lung cancer cells. In the in vitro study, FePt-Cys NPs induced a
      reactive oxygen species (ROS) burst, which suppressed the antioxidant protein
      expression and induced cell apoptosis. Furthermore, FePt-Cys NPs prevented the
      migration and invasion of H1975 and A549 cells. These changes were correlated
      with a dramatic decrease in MMP-2/9 expression and enhanced the cellular
      attachment. We demonstrated that FePt-Cys NPs promoted the effects of chemo
      radiation through activation of the caspase system and impairment of DNA damage
      repair. In the in vivo study, no severe allergies or drug-related deaths were
      observed and FePt-Cys NPs showed a synergistic effect with cisplatin and
      radiation. In conclusion, with good safety and efficacy, FePt-Cys NPs could
      therefore be potential sensitizers for chemoradiotherapy.

PMID- 29331423
TI  - Thymidylate synthase prompts metastatic progression through the dTMP associated
      EMT process in pancreatic ductal adenocarcinoma.
AB  - As a fundamental metabolic enzyme, anti-Thymidylate synthase (TS) strategy has
      been shown to be an effective therapy for human cancers. However, the genuine
      effects of TS in pancreatic ductal adenocarcinoma (PDA) are still conflicting. We
      systemically assessed the prognostic value and whether TS associated with
      malignant progression in PDA. Protein and mRNA expression level of TS were
      evaluated in en bloc PDA samples, the prognostic effect of TS expressed in
      cytoplasm or cytonuclear was determined separately in the first time. The impact
      of TS on tumor cell behaviors was assessed in in vitro assays, and the TS
      associated metastatic potential was further determined in two different PDA
      metastatic models. The retrospective clinical analysis firstly demonstrated that
      tumor cytonuclear TS expression was positively correlated with lymphatic
      metastasis and negatively correlated with the overall survival (OS) in PDA
      patients. The subsequent experiments further confirmed that TS depletion can
      effectively abate EMT (epithelial to mesenchymal) process in in vitro and decline
      most of the metastatic lesions in two different PDA mice models, and the
      deoxythymidine monophosphate (dTMP) biosynthesis malfunction resulted imbalanced
      dNTP pools may be the fundamental causation. Collectively, the present study
      suggested the prospective strategy of combined anti-TS scheme for metastatic PDA,
      and we strongly suggest further clinical standardization research with a large
      cohort to verify the prognostic value and the therapeutic potential of TS in PDA.

PMID- 29331424
TI  - Ultra-narrow surface lattice resonances in plasmonic metamaterial arrays for
      biosensing applications.
AB  - When excited over a periodic metamaterial lattice of gold nanoparticles (~
      100nm), localized plasmon resonances (LPR) can be coupled by a diffraction wave
      propagating along the array plane, which leads to a drastic narrowing of plasmon
      resonance lineshapes (down to a few nm full-width-at-half-maximum) and the
      generation of singularities of phase of reflected light. These phenomena look
      very promising for the improvement of performance of plasmonic biosensors, but
      conditions of implementation of such diffractively coupled plasmonic resonances,
      also referred to as plasmonic surface lattice resonances (PSLR), are not always
      compatible with biosensing arrangement implying the placement of the
      nanoparticles between a glass substrate and a sample medium (air, water). Here,
      we consider conditions of excitation and properties of PSLR over arrays of glass
      substrate-supported single and double Au nanoparticles (~ 100-200nm), arranged in
      a periodic metamaterial lattice, in direct and Attenuated Total Reflection (ATR)
      geometries, and assess their sensitivities to variations of refractive index (RI)
      of the adjacent sample dielectric medium. First, we identify medium (PSLRair,
      PSLRwat for air and water, respectively) and substrate (PSLRsub) modes
      corresponding to the coupling of individual plasmon oscillations at medium- and
      substrate-related diffraction cut-off edges. We show that spectral sensitivity of
      medium modes to RI variations is determined by the lattice periodicity in both
      direct and ATR geometries (~ 320nm per RIU change in our case), while substrate
      mode demonstrates much lower sensitivity. We also show that phase sensitivity of
      PSLR can exceed 105 degrees of phase shift per RIU change and thus outperform the
      relevant parameter for all other plasmonic sensor counterparts. We finally
      demonstrate the applicability of surface lattice resonances in plasmonic
      metamaterial arrays to biosensing using standard streptavidin-biotin affinity
      model. Combining advantages of nanoscale architectures, including drastic
      concentration of electric field, possibility of manipulation at the nanoscale
      etc, and high phase and spectral sensitivities, PSLRs promise the advancement of
      current state-of-the-art plasmonic biosensing technology toward single molecule
      label-free detection.

PMID- 29331425
TI  - Low-picomolar, label-free procalcitonin analytical detection with an electrolyte
      gated organic field-effect transistor based electronic immunosensor.
AB  - Herein a label-free immunosensor based on electrolyte-gated organic field-effect
      transistor (EGOFET) was developed for the detection of procalcitonin (PCT), a
      sepsis marker. Antibodies specific to PCT were immobilized on the poly-3
      hexylthiophene (P3HT) organic semiconductor surface through direct physical
      adsorption followed by a post-treatment with bovine serum albumin (BSA) which
      served as the blocking agent to prevent non-specific adsorption. Antibodies
      together with BSA (forming the whole biorecognition layer) served to selectively
      capture the procalcitonin target analyte. The entire immunosensor fabrication
      process was fast, requiring overall 45min to be completed before analyte sensing.
      The EGOFET immunosensor showed excellent electrical properties, comparable to
      those of bare P3HT based EGOFET confirming reliable biosensing with bio
      functional EGOFET immunosensor. The detection limit of the immunosensor was as
      low as 2.2pM and within a range of clinical relevance. The relative standard
      deviation of the individual calibration data points, measured on immunosensors
      fabricated on different chips (reproducibility error) was below 7%. The developed
      immunosensor showed high selectivity to the PCT analyte which was evident through
      control experiments. This report of PCT detection is first of its kind among the
      electronic sensors based on EGOFETs. The developed sensor is versatile and
      compatible with low-cost fabrication techniques.

PMID- 29331426
TI  - Hybrid porous thin films: Opportunities and challenges for sensing applications.
AB  - In this paper, the scientific progress in the field of thin film materials and
      their associated sensing technologies are described comprehensively to address
      the directions for future research and developments as per the need of modern-day
      technologies. To begin with, we briefly discussed the fundamental synthesis
      approaches for advanced thin films with an emphasis on the properties necessary
      for controlled fabrication (e.g., the elemental ratio and spatial arrangement).
      Subsequently, we explored the control, characterization, and optimization of
      hybrid porous thin films with respect to diverse sensing applications. The
      application of hybrid porous thin film materials has also been discussed in
      relation to the mechanisms used for biological, optical, electrical, acoustic,
      and other advanced sensing techniques (e.g., surface-enhanced Raman scattering
      (SERS)). Finally, conclusions are drawn to highlight the current status of thin
      film-based sensing technology along with its opportunities and challenges.

PMID- 29331427
TI  - Water-soluble mercury ion sensing based on the thymine-Hg2+-thymine base pair
      using retroreflective Janus particle as an optical signaling probe.
AB  - Herein, we report an optical sensing platform for mercury ions (Hg2+) in water
      based on the integration of Hg2+-mediated thymine-thymine (T-T) stabilization, a
      biotinylated stem-loop DNA probe, and a streptavidin-modified retroreflective
      Janus particle (SA-RJP). Two oligonucleotide probes, including a stem-loop DNA
      probe and an assistant DNA probe, were utilized. In the absence of Hg2+, the
      assistant DNA probe does not hybridize with the stem-loop probe due to their T-T
      mismatch, so the surface-immobilized stem-loop DNA probe remains a closed hairpin
      structure. In the presence of Hg2+, the DNA forms a double-stranded structure
      with the loop region via Hg2+-mediated T-T stabilization. This DNA hybridization
      induces stretching of the stem-loop DNA probe, exposing biotin. To translate
      these Hg2+-mediated structural changes in DNA probe into measurable signal, SA
      RJP, an optical signaling label, is applied to recognize the exposed biotin. The
      number of biospecifically bound SA-RJPs is proportional to the concentration of
      Hg2+, so that the concentration of Hg2+ can be quantitatively analyzed by
      counting the number of RJPs. Using the system, a highly selective and sensitive
      measurement of Hg2+ was accomplished with a limit of detection of 0.027nM.
      Considering the simplified optical instrumentation required for retroreflection
      based RJP counting, RJP-assisted Hg2+ measurement can be accomplished in a much
      easier and inexpensive manner. Moreover, the detection of Hg2+ in real drinking
      water samples including tap and commercial bottled water was successfully carried
      out.

PMID- 29331428
TI  - Heating enhanced sensitive and selective electrochemical detection of Hg2+ based
      on T-Hg2+-T structure and exonuclease III-assisted target recycling amplification
      strategy at heated gold disk electrode.
AB  - A sensitive and selective electrochemical Hg2+ sensor was developed based on T
      Hg2+-T structure and exonuclease (Exo) III -assisted target recycling
      amplification at heated gold disk electrode (HAuDE). First, a DNA signal probe P1
      was for the first time designed and labeled with ferrocene (Fc) near the attached
      SH-5'-end, so as to shorten the distance between Fc and the electrode and enhance
      the initial current of Fc compared with that labeled at the 3'-end far from the
      electrode. Then the signal amplification was achieved by Exo III-assisted Hg2+
      recycling. Briefly, the P1 was complementary to the assistant DNA P2 except the T
      T mismatches. In the presence of Hg2+, the P1 self-assembled on the HAuDE could
      hybridize with P2 and form DNA duplex with blunt end at the 3'- terminus,
      triggering Exo III to stepwise digest mononucleotides from the 3'-terminus of P1,
      ultimately liberating Hg2+ and P2, which could be "recycled", resulting in the
      digestion of a large amount of P1 and significantly decrease the amount of Fc.
      The electrochemical signal difference before and after digestion was proportional
      to the Hg2+ concentration. Furthermore, during the digestion period, the Exo III
      activity could be significantly increased by elevating the electrode temperature,
      great improving the sensitivity and efficiency for Hg2+ detection. A detection
      limit of 6.2 pM (S/N = 3) could be obtained with an electrode temperature of 40
      degrees C during 60min digestion period, which was lower ca. two magnitudes than
      that at 0 degrees C and one magnitude than that at 25 degrees C.

PMID- 29331429
TI  - Paper-based fluorescent sensor via aggregation induced emission fluorogen for
      facile and sensitive visual detection of hydrogen peroxide and glucose.
AB  - Hydrogen peroxide (H2O2), an important reactive oxygen species (ROS), is related
      to the oxidative stress in organisms, and plays important roles in a variety of
      cellular activities as well. So it is of crucial importance to develop sensitive
      and accurate sensing strategies to detect H2O2 in biological systems. Herein, by
      taking advantage of the unique emission characteristics of aggregation induced
      emission (AIE) fluorogens, we proposed a non-enzymatic fluorescence platform for
      facile and sensitive detection of H2O2, both in solution state using fluorescence
      spectrometer and on paper-based sensor via visual inspection. Through the
      reaction between L-cysteine and H2O2, the fluorescence of TPE-M-L, an AIE
      fluorogen formed between maleimide-functionalized tetraphenylethene (TPE-M) and L
      cysteine, is quenched, and highly sensitive non-enzymatic H2O2 assay is readily
      carried out. The limit of detection (LOD) of 10nM in solution state and 2.5MUM on
      paper-based sensor were obtained for H2O2 detection, which were superior or
      comparable to those previously reported in literature. Moreover, by integrating
      glucose oxidase with the AIE fluorogen of TPE-M-L, highly sensitive and selective
      glucose detection was also conveniently achieved both in solution state and on
      paper-based sensor by the as-proposed strategy, with the LODs of 50nM in solution
      state and 10MUM via visual observation, much better than those obtained by other
      fluorescence methods. The as-proposed sensing strategy was also successfully
      applied to assay glucose in human serum samples. Therefore, the paper-based
      fluorescence sensor exhibits the advantages of simple fabrication, high
      sensitivity and portability, and has great potential to be applied in on-site
      assay of H2O2 and glucose in real samples.

PMID- 29331431
TI  - Robust synchronization of master-slave chaotic systems using approximate model:
      An experimental study.
AB  - Robust synchronization of master slave chaotic systems are considered in this
      work. First an approximate model of the error system is obtained using the ultra
      local model concept. Then a Continuous Singular Terminal Sliding-Mode (CSTSM)
      Controller is designed for the purpose of synchronization. The proposed approach
      is output feedback-based and uses fixed-time higher order sliding-mode (HOSM)
      differentiator for state estimation. Numerical simulation and experimental
      results are given to show the effectiveness of the proposed technique.

PMID- 29331430
TI  - Disposable inkjet-printed electrochemical platform for detection of clinically
      relevant HER-2 breast cancer biomarker.
AB  - Rapidly fabricated, disposable sensor platforms hold tremendous promise for point
      of-care detection. Here, we present an inexpensive (< $0.25) fully inkjet printed
      electrochemical sensor with integrated counter, reference, and working electrodes
      that is easily scalable for commercial fabrication. The electrochemical sensor
      platform featured an inkjet printed gold working 8-electrode array (WEA) and
      counter electrode (CE), along with an inkjet -printed silver electrode that was
      chlorinated with bleach to produce a Ag/AgCl quasi-reference electrode (RE). As
      proof of concept, the electrochemical sensor was successfully applied for
      detection of clinically relevant breast cancer biomarker Human Epidermal Growth
      Factor Receptor 2 (HER-2). Capture antibodies were bound to a chemically modified
      surface on the WEA and placed into a microfluidic device. A full sandwich
      immunoassay was constructed following a simultaneous injection of target protein,
      biotinylated antibody, and polymerized horseradish peroxide labels into the
      microfluidic device housing the WEA. With an ultra fast assay time, of only
      15mins a clinically relevant limit of detection of 12pgmL-1 was achieved.
      Excellent reproducibility and sensitivity were observed through recovery assays
      preformed in human serum with recoveries ranging from 76% to 103%. These easily
      fabricated and scalable electrochemical sensor platforms can be readily adapted
      for multiplex detection following this rapid assay protocol for cancer
      diagnostics.

PMID- 29331432
TI  - Sliding mode control for a two-joint coupling nonlinear system based on extended
      state observer.
AB  - A two-joint coupling nonlinear system driven by pneumatic artificial muscles is
      introduced in this paper. A sliding mode controller with extended state observer
      is proposed to cope with nonlinearities and disturbances for the two-joint
      coupling nonlinear system. In addition, convergence of the extended state
      observer is presented and stability analysis of the closed-loop system is also
      demonstrated with the sliding mode controller. Lastly, some experiments are
      carried out to show the reality effectiveness of the proposed method.

PMID- 29331433
TI  - Receding horizon Hinfinity guaranteed cost tracking control for microwave heating
      medium with temperature-dependent permittivity.
AB  - This paper considers the temperature spectrum tracking control of microwave
      heating model, in the presence of asymmetrical input saturation, nonhomogeneous
      Neumann boundary condition and temperature-dependent permittivity. The sufficient
      condition for the existence of receding horizon Hinfinity guaranteed cost control
      is proposed based on the derived finite-dimensional ordinary differential
      equation (ODE) error model. Furthermore, by on-line updating and solving linear
      matrix inequalities (LMIs) optimization problem, the constrained tracking
      controller can be obtained in the sense of minimizing Hinfinity norm and
      satisfying the quadratic cost performance. The proposed control strategy is
      implemented on a one-dimensional cavity heating model and its performance is
      evaluated through the simulation.

PMID- 29331434
TI  - Fault diagnosis of rolling element bearing using a new optimal scale morphology
      analysis method.
AB  - Periodic transient impulses are key indicators of rolling element bearing
      defects. Efficient acquisition of impact impulses concerned with the defects is
      of much concern to the precise detection of bearing defects. However, transient
      features of rolling element bearing are generally immersed in stochastic noise
      and harmonic interference. Therefore, in this paper, a new optimal scale
      morphology analysis method, named adaptive multiscale combination morphological
      filter-hat transform (AMCMFH), is proposed for rolling element bearing fault
      diagnosis, which can both reduce stochastic noise and reserve signal details. In
      this method, firstly, an adaptive selection strategy based on the feature energy
      factor (FEF) is introduced to determine the optimal structuring element (SE)
      scale of multiscale combination morphological filter-hat transform (MCMFH).
      Subsequently, MCMFH containing the optimal SE scale is applied to obtain the
      impulse components from the bearing vibration signal. Finally, fault types of
      bearing are confirmed by extracting the defective frequency from envelope
      spectrum of the impulse components. The validity of the proposed method is
      verified through the simulated analysis and bearing vibration data derived from
      the laboratory bench. Results indicate that the proposed method has a good
      capability to recognize localized faults appeared on rolling element bearing from
      vibration signal. The study supplies a novel technique for the detection of
      faulty bearing.

PMID- 29331435
TI  - Complications of chronic total occlusion percutaneous coronary intervention:
      Subepicardial hematoma.
AB  - A 67-year-old man with coronary artery disease and previous coronary underwent
      successful Guideliner reverse CART percutaneous coronary intervention of a
      chronic total occlusion of the right coronary artery. He later developed evidence
      of myocardial ischemia, and imaging, including angiogram, echocardiogram, and
      cardiac computed tomography revealing active dye extravasation from the
      previously normal RV marginal branches, in addition to a large subepicardial
      hematoma. Despite these dramatic findings, the patient remained hemodynamically
      stable and pain-free, with resolving ECG changes. Thus, with close clinical
      observation, the patient did not undergo pericardiocentesis or other invasive
      procedures, and was discharged home safely. This review evaluates the
      complications of CTO-PCI, with a focus on subepicardial hematomas, discussing
      diagnosis and management of this highly morbid complication.

PMID- 29331436
TI  - Jetstream Atherectomy System treatment of femoropopliteal arteries: Results of
      the post-market JET Registry.
AB  - OBJECTIVES: To report on procedural, safety, and effectiveness outcomes of real
      world practice with the Jetstream rotational atherectomy system for treatment of
      femoropopliteal artery lesions. BACKGROUND: Safety and effectiveness of treatment
      with the Jetstream device has been demonstrated in clinical trials, but outcomes
      during real-world clinical practice have yet to be examined. METHODS: 241
      patients (66% male, mean age 67years, 41% diabetes; Rutherford 1-3) with de novo
      or restenotic (non-stent) femoropopliteal lesions >=4cm in length were recruited.
      Major adverse events (MAE), defined as amputation, death, target lesion/vessel
      revascularization (TLR/TVR), myocardial infarction, or angiographic distal
      embolization that required a separate intervention; and binary restenosis were
      assessed at 30days and 12months. RESULTS: The mean (+/-SD) lesion length was
      16.4+/-13.6cm; 35% of patients received adjunctive stents. Procedural success was
      achieved for 98.3% of lesions. The 30-day MAE rate was 2% (5/219; 2 TLR/TVR and 3
      distal embolization); there were no deaths, index limb amputations, or myocardial
      infarctions. At 12months, the overall estimated freedom from TLR/TVR was 81.7%
      and 77.2% (44/57) of patients were free from duplex ultrasound-assessed
      restenosis. Efficacy and patency in a diabetic subset were similar to those of
      the overall cohort, while maintaining a similar safety profile. CONCLUSION: In a
      cohort reflecting real-world practice, the Jetstream Atherectomy System
      demonstrated a high procedural success rate with a low rate of complications and
      reinterventions, especially given the relatively long lesions studied.

PMID- 29331437
TI  - Influence of operator experience and PCI volume on transfemoral access
      techniques: A collaboration of international cardiovascular societies.
AB  - INTRODUCTION: Transfemoral access (TFA) is widely used for coronary angiography
      and percutaneous coronary intervention (PCI). The influence of operator age,
      gender, experience, and procedural volume on performance of femoral arterial
      access has not been studied. METHODS: A survey instrument was developed and
      distributed via e-mail from professional societies to interventional
      cardiologists worldwide from March to December 2016. RESULTS: A total of 988
      physicians from 88 countries responded to the survey. TFA is the preferred
      approach for patients with cardiogenic shock, left main or bifurcation PCI, and
      procedures with mechanical circulatory support. Older (<50years: 56.4%;
      >=50years: 66.8%, p<0.0039) and high PCI volume operators (<100 PCI: 57.3%; 100
      299 PCI: 58.7%; >=300 PCI: 64.3%, p<0.134) preferred palpation only without
      imaging (fluoroscopy or ultrasound (US)) for TFA. Most respondents preferred not
      to use micropuncture needle to puncture the femoral artery. Older (>=50years:
      64.4%; <50years: 71.5%, p<0.04) and high PCI volume operators (>=300 PCI: 64.1%;
      100-299 PCI: 72.6%; <100 PCI: 67.9%, p<0.072) tended not to perform femoral
      angiography (FA). Of those performing FA, the majority opted to do it at the end
      of the procedure. CONCLUSION: Despite best practice guideline recommendations,
      older and high PCI volume interventional cardiologists prefer not to use imaging
      for femoral access or perform femoral angiography during TF procedures. These
      data highlight opportunities to further reduce TFA complications.

PMID- 29331438
TI  - Characterization of surface properties of glass vials used as primary packaging
      material for parenterals.
AB  - The appropriate selection of adequate primary packaging, such as the glass vial,
      rubber stopper, and crimp cap for parenteral products is of high importance to
      ensure product stability, microbiological quality (integrity) during storage as
      well as patient safety. A number of issues can arise when inadequate vial
      material is chosen, and sole compliance to hydrolytic class I is sometimes not
      sufficient when choosing a glass vial. Using an appropriate pre-treatment, such
      as surface modification or coating of the inner vial surface after the vial
      forming process the glass container quality is often improved and interactions of
      the formulation with the surface of glass may be minimized. This study aimed to
      characterize the inner surface of different type I glass vials (Exp33, Exp51,
      Siliconized, TopLyoTM and Type I plus(r)) at the nanoscale level. All vials were
      investigated topographically by colorimetric staining and Scanning Electron
      Microscopy (SEM). Glass composition of the surface was studied by Time-of-Flight 
      Secondary Ion Mass Spectrometry (ToF-SIMS) and X-ray Photoelectron Spectroscopy
      (XPS), and hydrophobicity/hydrophilicity of the inner surface was assessed by dye
      tests and surface energy measurements. All containers were studied unprocessed,
      as received from the vendor, i.e. in unwashed and non-depyrogenized condition.
      Clear differences were found between the different vial types studied. Especially
      glass vials without further surface modifications, like Exp33 and Exp51 vials,
      showed significant (I) vial-to-vial variations within one vial lot as well as
      (II) variations along the vertical axis of a single vial when studying topography
      and chemical composition. In addition, differences and heterogeneity in surface
      energy were found within a given tranche (circumferential direction) of Exp51 as
      well as Type I plus(r) vials. Most consistent quality was achieved with TopLyoTM
      vials. The present comprehensive characterization of surface properties of the
      different vial types may serve as basis to further guide the selection of
      adequate primary packaging based on the desired quality target product profile
      and to support studies of glass surface interactions with formulations. The
      proposed analytical method panel can be used for characterization of future glass
      vials either before delivery to the manufacturer or drug product manufacturing.

PMID- 29331439
TI  - Interactions of dimethylaminoethyl methacrylate copolymer with non-acidic drugs
      demonstrated high solubilization in vitro and pronounced sustained release in
      vivo.
AB  - Recent work demonstrated remarkable solubilization effects of methacrylate
      copolymer Eudragit EPO (EPO) not only with acidic drugs but interestingly also
      with poorly soluble basic compounds. The current work studied EPO-mediated
      solubilization effects first in vitro using felodipine (FLP) and tamoxifen (TMX)
      as model compounds. EPO-containing solutions were subsequently compared in a rat
      pharmacokinetic study against reference solutions and suspensions. Surprisingly,
      solution formulations with EPO did not result in an increased relative oral
      bioavailability. Exposure was reduced for both drugs and plasma-profiles of the
      EPO solutions showed a delayed and lower maximum plasma concentration compared to
      the reference formulations. This sustained in vivo release was likely due to
      combined effects of strong drug-polymer interactions and pH-dependent
      precipitation of the polymer in the rat intestine. Remarkable was that in vitro
      drug-polymer coprecipitates did not reveal crystalline drug by polarized light
      microscopy. Thus, such a formulation approach provides a rather simple
      opportunity to modify drug release in vivo. However, this may be rather an
      approach for preclinical formulations, if high peak-to-trough ratios of plasma
      levels are problematic regarding adverse effects related to Cmax or if plasma
      concentrations drop too fast below required pharmacological concentrations.

PMID- 29331440
TI  - The effect of bilateral eye-movements versus no eye-movements on sexual
      fantasies.
AB  - BACKGROUND AND OBJECTIVES: Bilateral eye-movements (EMs) and visual mental
      imagery both require working memory resources. When performed together, they
      compete for these resources, which can cause various forms of mental imagery to
      become impaired (e.g., less vivid). This study aimed to examine whether EMs
      impair sexual fantasies (a form of mental imagery) in the same manner. METHODS:
      Eighty undergraduates (40 males, 40 females) took part in four counterbalanced
      conditions: (1) EMs and an experience-based sexual fantasy; (2) EMs and an
      imagination-based sexual fantasy; (3) experience-based sexual fantasy only; and
      (4) imagination-based sexual fantasy only. In each condition, the vividness,
      emotionality, and arousability of the sexual fantasy were rated pre- and post
      task. All three variables were predicted to decrease in the EM conditions.
      RESULTS: Sexual fantasies were reported as less vivid, positive, and arousing
      after performing concurrent EMs relative to fantasising only, for both memory-
      and imagination-based sexual fantasies. There were no gender differences. Demand
      did not appear to account for the effects. LIMITATIONS: Self-report measures were
      used rather than objective measures. Working memory taxation and capacity were
      not directly assessed. Also, negatively appraised sexual fantasies were not
      targeted and a 'no intervention' control was not included. CONCLUSIONS: Bilateral
      EMs were effective at impairing the phenomenological properties of sexual mental
      imagery, extending the literature on EM effects. Given the potential clinical
      implications, future research should focus on validating and extending these
      results, for example, by targeting negatively appraised sexual fantasies
      (including problematic and offense-related) and incorporating a 'no intervention'
      condition.

PMID- 29331441
TI  - Poor oral intake in a late preterm twin - usual symptom with an unusual
      diagnosis.
AB  - BACKGROUND: At three weeks of age, a previous 34 weeks' gestation male infant
      (twin A) was transferred to our regional perinatal center (RPC) with complaints
      of poor oral feeding and intermittent tachypnea. Twin B was discharged at 37
      weeks with an uneventful course. CASE: Twin A briefly required respiratory
      support but continued to have difficulty transitioning from gavage to oral
      feeding. Initially, his inability to feed orally was thought to be secondary to
      nasal congestion and prematurity, but with worsening respiratory distress he was
      transferred for further evaluation and management. DIAGNOSIS & CONCLUSION: On
      admission to RPC, the examination prompted a cardiac assessment which revealed a
      large aortic-pulmonary window type II. After surgery, the infant quickly improved
      and went home on-demand oral feeds. Cardiac lesions are more common in
      monochorionic twins but should be suspected in dichorionic twins especially if
      one twin has a normal course.

PMID- 29331442
TI  - Coffee consumption and risk of hypertension in the SUN Project.
AB  - BACKGROUND & AIMS: Evidence on coffee consumption and its association with the
      incidence of hypertension is still inconsistent. The aim of this study was to
      examine the association of regular or decaffeinated coffee consumption with the
      risk of developing hypertension in a middle-aged Mediterranean cohort. METHODS:
      The SUN Project is a prospective open cohort with more than 22,500 Spanish
      university graduates. For the present study, we analyzed data from 13,374
      participants initially free of hypertension (mean follow-up 9.1 years). The
      consumption of regular and decaffeinated coffee was obtained at baseline using a
      previously validated semi-quantitative food frequency questionnaire. Validated,
      self-reported medical diagnoses of hypertension were collected biennially. We
      used Cox regression models to estimate hazard ratios (HR) and 95% confidence
      intervals (95% CI) for incident hypertension according to baseline coffee
      consumption. We assessed the interaction with sex and baseline adherence to the
      Mediterranean diet. RESULTS: Among 121,397 person-years of follow-up, a total of
      1757 participants developed hypertension. Overall, coffee consumption -either
      caffeinated or decaffeinated- was not significantly associated with the risk of
      hypertension. Only among women, higher consumption of regular coffee was
      associated with a 26% lower risk of hypertension (>=2 cups/d vs. never/seldom,
      95% CI 9%-39%; p for interaction: 0.0236). Women with a low baseline adherence to
      the Mediterranean diet showed the strongest risk reduction (HR >= 2 cups/d vs.
      never/seldom 0.58, 95% CI (0.41-0.82) p for interaction = 0.0452). CONCLUSION: In
      the SUN project we found an inverse association between regular coffee
      consumption and the risk of hypertension in women, which was strongest among
      women with a suboptimal food pattern (low adherence to the Mediterranean diet).

PMID- 29331443
TI  - Strengthen federal regulation of laboratory-developed and direct-to-consumer
      genetic testing.

PMID- 29331444
TI  - Call for action: Nurses must play a critical role to enhance health literacy.

PMID- 29331445
TI  - The vital role of school nurses in ensuring the health of our nation's youth.

PMID- 29331446
TI  - Intolerance of uncertainty: Neural and psychophysiological correlates of the
      perception of uncertainty as threatening.
AB  - Intolerance of uncertainty (IU) reflects the perception of uncertainty as
      threatening, regardless of the true probability of threat. IU is elevated in
      various forms of psychopathology, uniquely associated with anxiety and depression
      symptoms after controlling for related constructs, and prospectively predicts
      symptoms. Given the ubiquity of uncertainty in daily life and the clinical
      implications of IU, recent work has begun to investigate the neural and
      psychophysiological correlates of IU. This review summarizes the existing
      literature and integrates findings within a mechanistic neural model of
      responding to uncertainty. IU is associated with heightened reactivity to
      uncertainty reflected in greater activity of the anterior insula and amygdala,
      alterations in neural responses to rewards and errors evident in event-related
      potentials, a mixed pattern of startle responses to uncertain threat, and
      deficiencies in safety learning indexed by startle and skin conductance
      responding. These findings provide evidence of disruptions in several domains of
      responding to uncertainty, threat, and reward associated with IU that may confer
      risk for the development of psychopathology. Significant attention is devoted to
      recommendations for future research, including consideration of the complex
      interplay of IU with emotion regulation, cognitive control, and reward
      processing.

PMID- 29331448
TI  - Surveillance After Endovascular Treatment for Blunt Thoracic Aortic Injury.

PMID- 29331451
TI  - Sporotrichoid non-tuberculous mycobacterial infections following anti-TNF
      treatment.

PMID- 29331447
TI  - Sharp-wave ripples as a signature of hippocampal-prefrontal reactivation for
      memory during sleep and waking states.
AB  - It is widely believed that memories that are encoded and retrieved during waking
      behavior are consolidated during sleep. Recent studies on the interactions
      between the hippocampus and the prefrontal cortex have greatly advanced our
      understanding of the physiological bases of these memory processes. Although
      hippocampal-prefrontal network activity differs in many aspects during waking and
      sleep states, here we review evidence that hippocampal sharp-wave ripples (SWRs)
      emerge as a common neurophysiological pattern in both states, facilitating
      communication between these two regions via coordinated reactivation of stored
      memory information. We further consider whether sleep and awake reactivation
      mediate similar memory processes or have different mnemonic functions, and the
      mechanistic role of this cross-regional dialogue in learning and memory. Finally,
      we provide an integrated view of how these two forms of reactivation might work
      together to support spatial learning and memory.

PMID- 29331450
TI  - Mapping stimulus feature selectivity in macaque V1 by two-photon Ca2+ imaging:
      Encoding-model analysis of fluorescence responses to natural movies.
AB  - In vivo calcium (Ca2+) imaging using two-photon microscopy allows activity to be
      monitored simultaneously from hundreds of individual neurons within a local
      population. While this allows us to gain important insights into how cortical
      neurons represent sensory information, factors such as photo-bleaching of the
      Ca2+ indicator limit imaging duration (and thus the numbers of stimuli that can
      be tested), which in turn hampers the full characterization of neuronal response
      properties. Here, we demonstrate that using an encoding model combined with
      presentation of natural movies results in detailed characterization of receptive
      field (RF) properties despite the relatively short time for data collection.
      During presentation of natural movie clips to macaque monkeys, we recorded
      fluorescence signals from primary visual cortex (V1) neurons that had been loaded
      with a Ca2+ indicator. For each recorded neuron, we constructed an encoding model
      that comprised an array of motion-energy filters that tiled over the RFs. We
      optimized the weight of each filter's output so that the linear sum of the
      outputs across the filters mimicked the neuron's Ca2+-signal responses. These
      models were able to predict the neural responses to a different set of natural
      movies with a significant degree of accuracy. Moreover, the orientation tunings
      of neurons simulated by the model were highly correlated with those
      experimentally obtained when grating stimuli were presented to the monkeys. The
      model predictions were also consistent with what is known about spatial frequency
      tunings, the structure of excitatory subfields of RFs (i.e., classical RFs), and
      functional maps for these RF properties in V1. Further analysis revealed a new
      aspect of V1 functional architecture; the extent and distribution of suppressive
      RF subfields varied among nearby neurons, while those for excitatory subfields
      were shared. Thus, applying our encoding-model analysis to two-photon Ca2+
      imaging of neuronal responses to natural movies provides a reliable and efficient
      means of analyzing a wide range of RF properties in multiple neurons imaged in a
      local region.

PMID- 29331449
TI  - Quantifying axonal responses in patient-specific models of subthalamic deep brain
      stimulation.
AB  - Medical imaging has played a major role in defining the general anatomical
      targets for deep brain stimulation (DBS) therapies. However, specifics on the
      underlying brain circuitry that is directly modulated by DBS electric fields
      remain relatively undefined. Detailed biophysical modeling of DBS provides an
      approach to quantify the theoretical responses to stimulation at the cellular
      level, and has established a key role for axonal activation in the therapeutic
      mechanisms of DBS. Estimates of DBS-induced axonal activation can then be coupled
      with advances in defining the structural connectome of the human brain to provide
      insight into the modulated brain circuitry and possible correlations with
      clinical outcomes. These pathway-activation models (PAMs) represent powerful
      tools for DBS research, but the theoretical predictions are highly dependent upon
      the underlying assumptions of the particular modeling strategy used to create the
      PAM. In general, three types of PAMs are used to estimate activation: 1) field
      cable (FC) models, 2) driving force (DF) models, and 3) volume of tissue
      activated (VTA) models. FC models represent the "gold standard" for analysis but
      at the cost of extreme technical demands and computational resources.
      Consequently, DF and VTA PAMs, derived from simplified FC models, are typically
      used in clinical research studies, but the relative accuracy of these
      implementations is unknown. Therefore, we performed a head-to-head comparison of
      the different PAMs, specifically evaluating DBS of three different axonal
      pathways in the subthalamic region. The DF PAM was markedly more accurate than
      the VTA PAMs, but none of these simplified models were able to match the results
      of the patient-specific FC PAM across all pathways and combinations of stimulus
      parameters. These results highlight the limitations of using simplified
      predictors to estimate axonal stimulation and emphasize the need for novel
      algorithms that are both biophysically realistic and computationally simple.

PMID- 29331452
TI  - Design, synthesis and evaluation of gamma-turn mimetics as LSD1-selective
      inhibitors.
AB  - Lysine-specific demethylase 1 (LSD1) is an attractive molecular target for cancer
      therapy. We have previously reported potent LSD1-selective inhibitors (i.e.,
      NCD18, NCD38, and their analogs) consisting of trans-2-phenylcyclopropylamine
      (PCPA) or trans-2-arylcyclopropylamine (ACPA) and a lysine moiety that could form
      a gamma-turn structure in the active site of LSD1. Herein we report the design,
      synthesis and evaluation of gamma-turn mimetic compounds for further improvement
      of LSD1 inhibitory activity and anticancer activity. Among a series of gamma-turn
      mimetic compounds synthesized by a Mitsunobu-reaction-based amination strategy,
      we identified 1n as a potent and selective LSD1 inhibitor. Compound 1n induced
      cell cycle arrest and apoptosis through histone methylation in human lung cancer
      cells. The gamma-turn mimetics approach should offer new insights into drug
      design for LSD1-selective inhibitors.

PMID- 29331454
TI  - Reply.

PMID- 29331453
TI  - Are privacy-enhancing technologies for genomic data ready for the clinic? A
      survey of medical experts of the Swiss HIV Cohort Study.
AB  - PURPOSE: Protecting patient privacy is a major obstacle for the implementation of
      genomic-based medicine. Emerging privacy-enhancing technologies can become key
      enablers for managing sensitive genetic data. We studied physicians' attitude
      toward this kind of technology in order to derive insights that might foster
      their future adoption for clinical care. METHODS: We conducted a questionnaire
      based survey among 55 physicians of the Swiss HIV Cohort Study who tested the
      first implementation of a privacy-preserving model for delivering genomic test
      results. We evaluated their feedback on three different aspects of our model:
      clinical utility, ability to address privacy concerns and system usability.
      RESULTS: 38/55 (69%) physicians participated in the study. Two thirds of them
      acknowledged genetic privacy as a key aspect that needs to be protected to help
      building patient trust and deploy new-generation medical information systems. All
      of them successfully used the tool for evaluating their patients'
      pharmacogenomics risk and 90% were happy with the user experience and the
      efficiency of the tool. Only 8% of physicians were unsatisfied with the level of
      information and wanted to have access to the patient's actual DNA sequence.
      CONCLUSION: This survey, although limited in size, represents the first
      evaluation of privacy-preserving models for genomic-based medicine. It has
      allowed us to derive unique insights that will improve the design of these new
      systems in the future. In particular, we have observed that a clinical
      information system that uses homomorphic encryption to provide clinicians with
      risk information based on sensitive genetic test results can offer information
      that clinicians feel sufficient for their needs and appropriately respectful of
      patients' privacy. The ability of this kind of systems to ensure strong security
      and privacy guarantees and to provide some analytics on encrypted data has been
      assessed as a key enabler for the management of sensitive medical information in
      the near future. Providing clinically relevant information to physicians while
      protecting patients' privacy in order to comply with regulations is crucial for
      the widespread use of these new technologies.

PMID- 29331455
TI  - Femtosecond laser-assisted cataract surgery in pediatric patients.
AB  - Pediatric cataract surgery poses a significant challenge for the cataract
      surgeon, in part because an elastic anterior capsule can make capsulorhexis
      difficult. With the use of femtosecond laser-assisted cataract surgery (FLACS),
      however, the continuous curvilinear capsulorhexis can be made with predictable
      size, circular shape, centration, and accuracy. In addition, topical anesthesia
      can be used for the FLACS docking procedure in cooperative children above 6 years
      of age, using transparent adhesive polyurethane film segments.

PMID- 29331456
TI  - Vocalization as an indicator of estrus climax in Holstein heifers during natural
      estrus and superovulation.
AB  - The reliable detection of estrus is an important scientific and practical
      challenge in dairy cattle farming. Female vocalization may indicate reproductive
      status, and preliminary evidence suggests that this information can be used to
      detect estrus in dairy cattle. The aim of this study was to associate the changes
      in the vocalization rate of dairy heifers with behavioral estrus indicators as
      well as test the influence of the type of estrus (natural estrus vs.
      superovulation-induced estrus). We analyzed 6 predefined estrus-related behavior
      patterns (standing to be mounted, head-side mounting, active mounting, chin
      resting, being mounted while not standing, and active sniffing in the anogenital
      region) and vocalization rates in the peri-estrus period (day of estrus +/- 1 d)
      of 12 German Holstein heifers using audio-visual recordings. Each heifer was
      observed under natural estrus and a consecutive superovulation induced by FSH and
      cloprostenol. Estrus was determined by behavioral patterns and confirmed by
      clinical examination (vaginoscopy and ultrasound imaging of the ovaries) as well
      as by the concentration of peripheral progesterone. Estrus behavior and
      vocalization rates were analyzed in 3-h intervals (an average of 19 intervals for
      each heifer), and an estrus score was calculated based on the 6 behaviors. The
      interval with the highest estrus score (I0) was considered the estrus climax. We
      demonstrated similar time courses for the estrus score and vocalization rate
      independent of estrus type. However, in natural estrus, the maximum vocalization
      rate (+/-SE) occurred in the interval before estrus climax (I-1; 42.58 +/- 21.89)
      and was significantly higher than that in any other interval except estrus climax
      (I0; 27.58 +/- 9.76). During natural estrus, the vocalization rate was
      significantly higher within the interval before estrus climax (I-1; 42.58 +/-
      21.89 vs. 11.58 +/- 5.51) than under superovulation. The results underscore the
      potential use of vocalization rate as a suitable indicator of estrus climax in
      automated estrus detection devices. Further studies and technical development are
      required to record and process individual vocalization rates.

PMID- 29331457
TI  - Effect of the concentration of circulating prolactin on dairy cows'
      responsiveness to domperidone injection.
AB  - The objective of this study was to determine whether the responsiveness of the
      mammary gland to prolactin (PRL) is affected by the concentration of the hormone.
      After 1 pre-experimental week (d -7 to -1), 18 Holstein cows in mid to late
      lactation were injected intramuscularly twice daily with either 0.5 mg of
      quinagolide (QN) or 2 mL of water (control) for 2 wk (d 1 to 14; treatment
      period). After the treatment period, all cows received daily subcutaneous
      injections of 300 mg of domperidone (DOMP) for 3 wk (d 15 to 35; DOMP period).
      The cows were monitored for an additional 2 wk as a posttreatment period (d 36 to
      49). Blood and milk samples were collected 3 times per week. Additionally, blood
      samples were collected during the a.m. milking on d -4, 14, and 35. Milk
      production was not affected by QN during the treatment period but was increased
      during the DOMP and posttreatment periods in the QN cows. With respect to milk
      composition, the treatments affected only the protein content, which was greater
      in the QN cows during the treatment period. Blood PRL concentration declined
      during QN injections and was lower in the QN cows than in the control cows
      between d 5 and 14. The basal concentration of PRL was increased by DOMP
      injections during the DOMP and posttreatment periods but was not affected by
      previous QN injections. Prolactin concentration in milk was not affected by the
      QN treatments but was increased by DOMP injections during the DOMP and
      posttreatment periods. Milking-induced PRL release was decreased by QN on d 14.
      On d 35, milking did not induce a significant release of PRL above the baseline
      for both treatments. In conclusion, the results of this experiment support the
      contention that the mammary gland's responsiveness to PRL is modulated by the
      previous level of the hormone.

PMID- 29331458
TI  - Genetic correlations between methane production and fertility, health, and body
      type traits in Danish Holstein cows.
AB  - Our aim was to investigate the genetic correlations between CH4 production and
      body conformation, fertility, and health traits in dairy cows. Data were
      collected from 10 commercial Holstein herds in Denmark, including 5,758 cows with
      records for body conformation traits, 7,390 for fertility traits, 7,439 for
      health traits, and 1,397 with individual CH4 measurements. Methane production was
      measured during milking in automatic milking systems, using a sniffer approach.
      Correlations between CH4 and several different traits were estimated. These
      traits were interval between calving and first insemination, interval between
      first and last insemination, number of inseminations, udder diseases, other
      diseases, height, body depth, chest width, dairy character, top line, and body
      condition score. Bivariate linear models were used to estimate the genetic
      parameters within and between CH4 and the other traits. In general, the genetic
      correlations between CH4 and the traits investigated were low. The heritability
      of CH4 was 0.25, and ranged from 0.02 to 0.07 for fertility and health traits,
      and from 0.17 to 0.74 for body conformation traits. Further research with a
      larger data set should be performed to more accurately establish how CH4 relates
      to fertility, health, and body conformation traits in dairy cattle. This will be
      useful in the design of future breeding goals that consider the production of
      CH4.

PMID- 29331459
TI  - Garlic (Allium sativum L.) fed to dairy cows does not modify the cheese-making
      properties of milk but affects the color, texture, and flavor of ripened cheese.
AB  - Garlic and garlic components have recently been proposed as ruminal activity
      modulators to reduce the enteric methane emissions of ruminants, but little is
      known of their influence on milk coagulation properties, nutrient recovery,
      cheese yield, and sensorial and rheological characteristics of milk and cheese.
      The present study assessed the effects of garlic and diallyl sulfide supplements
      on dry matter intake (DMI), productive performance, milk coagulation properties,
      cheese yield, milk and cheese sensory profiles, and rheological characteristics.
      Four dairy cows were fed a total mixed ration either alone (control) or
      supplemented with 100 or 400 g/d of garlic cloves or 2 g/d of diallyl sulfide in
      4 consecutive experimental periods in a 4 * 4 Latin square design. The diallyl
      sulfide dose was established to provide approximately the same amount of allyl
      thiosulfinate compounds as 100 g of fresh garlic cloves. The total mixed ration
      was composed of 0.29 corn silage, 0.23 corn-barley mixture, 0.17 sunflower
      soybean mixture, 0.12 alfalfa hay, 0.12 grass hay, 0.04 sugar beet pulp, and 0.02
      other additives, and contained 0.253 starch, 0.130 crude protein, and 0.375
      neutral detergent fiber, on a dry matter basis. Each experimental period
      consisted of 7 d of transition and 14 d of treatment. On d 18 and 21 of each
      period, milk samples (10 L) were collected from each cow for chemical analysis
      and cheese-making. The organoleptic properties of the milk and 63-d-ripened
      cheeses were assessed by a panel of 7 trained sensory evaluators. The
      experimental treatments had no effects on DMI, milk yield, feed efficiency (milk
      yield/DMI), milk coagulation properties, nutrient recovery, or cheese yield.
      Garlic-like aroma, taste, and flavor of milk and cheese were significantly
      influenced by the treatments, particularly the highest dose of garlic cloves, and
      we found close exponential relationships between milk and cheese for garlic-like
      aroma (R2 = 0.87) and garlic-like flavor (R2 = 0.79). Diallyl sulfide and 400 g/d
      of garlic cloves resulted in lower pH, shear force, and shear work of ripened
      cheeses compared with the other treatments. Garlic cloves and diallyl sulfide had
      opposite effects on cheese color indices. We conclude that adding 400 g/d of
      garlic to the feed of lactating dairy cows highly influences the sensory and
      rheological characteristics of cheese.

PMID- 29331460
TI  - Inhibition of Shigella sonnei-induced epithelial barrier disruption by surface
      layer associated proteins of lactobacilli from Chinese fermented food.
AB  - Surface-layer associated proteins (SLAP) of Lactobacillus paracasei ssp.
      paracasei M5-L and Lactobacillus casei Q8-L were examined to identify the
      functional basis for their protection within intestinal epithelial cells. The
      results showed that SLAP of M5-L and Q8-L remained active in a trypsin solution
      and retained a 45-kDa protein band, similar to that observed in controls. In
      contrast, under conditions of simulated gastric juice, the SLAP were partially
      degraded. Inhibitory effects of SLAP on adherence of Shigella sonnei to HT-29
      cells were assessed with use of exclusion, competition, and replacement assays.
      In response to M5-L at 50 MUg/mL SLAP, an inhibition ratio of 33% was obtained,
      while for Q8-L at 400 MUg/mL SLAP, the inhibition ratio was 48%. Hoechst 33258
      test results showed that cells infected with S. sonnei and co-incubated with SLAP
      of M5-L and Q8-L were only partially apoptotic, with apoptosis rates of 37.67 and
      43.67%, respectively. These levels of apoptosis were substantially lower than
      that observed with cells infected with S. sonnei alone. In addition, the SLAP of
      Q8-L and M5-L reduced downstream caspase-1 activity and further modified
      apoptotic cell damage. Finally, SLAP of M5-L and Q8-L were also able to prevent
      S. sonnei-induced membrane damage by inhibiting delocalization of zonula
      occludens (ZO)-1 and reducing the amount of occludin produced by S. sonnei.

PMID- 29331461
TI  - Stabilizing vitamin D3 using the molten globule state of alpha-lactalbumin.
AB  - alpha-Lactalbumin (alpha-LA) is the second most abundant bovine whey protein. It
      has been intensively studied because of its readiness to populate the molten
      globular (MG) state, a partially folded state with native levels of secondary
      structure but loss of tertiary structure. The MG state of alpha-LA exposes a
      significant number of hydrophobic patches that could be used to bind and
      stabilize small hydrophobic molecules such as vitamin D3 (vitD). Accordingly, we
      tested the ability of alpha-LA to stabilize vitD in a pH interval from 7.4 to 2;
      over this pH interval, alpha-LA transitions from the folded state to the MG
      state. The MG state stabilized vitD better than the folded state and was superior
      to the major bovine whey protein beta-lactoglobulin (beta-LG), which is known to
      stabilize vitD. At pH 7.4, beta-LG and alpha-LA stabilized vitD to the same
      extent. Tryptophan fluorescence quenching measurements indicated that alpha-LA
      has one binding site at pH 7.4 but acquires an additional binding site when the
      pH is lowered to pH 2 to 4. Stability measurements of the vitD in the alpha-LA
      vitD complex at different temperatures suggest that UHT processing would lead to
      little loss of vitD. This study demonstrates the potential of alpha-LA as a
      component in vitD fortification, particularly for low pH applications.

PMID- 29331462
TI  - Genetic background of methane emission by Dutch Holstein Friesian cows measured
      with infrared sensors in automatic milking systems.
AB  - International environmental agreements have led to the need to reduce methane
      emission by dairy cows. Reduction could be achieved through selective breeding.
      The aim of this study was to quantify the genetic variation of methane emission
      by Dutch Holstein Friesian cows measured using infrared sensors installed in
      automatic milking systems (AMS). Measurements of CH4 and CO2 on 1,508 Dutch
      Holstein Friesian cows located on 11 commercial dairy farms were available.
      Phenotypes per AMS visit were the mean of CH4, mean of CO2, mean of CH4 divided
      by mean of CO2, and their log10-transformations. The repeatabilities of the log10
      transformated methane phenotypes were 0.27 for CH4, 0.31 for CO2, and 0.14 for
      the ratio. The log10-transformated heritabilities of these phenotypes were 0.11
      for CH4, 0.12 for CO2, and 0.03 for the ratio. These results indicate that
      measurements taken using infrared sensors in AMS are repeatable and heritable
      and, thus, could be used for selection for lower CH4 emission. Furthermore, it is
      important to account for farm, AMS, day of measurement, time of day, and
      lactation stage when estimating genetic parameters for methane phenotypes.
      Selection based on log10-transformated CH4 instead of the ratio would be expected
      to give a greater reduction of CH4 emission by dairy cows.

PMID- 29331463
TI  - Discriminating aging and protein-to-fat ratio in Cheddar cheese using sensory
      analysis and a potentiometric electronic tongue.
AB  - The objectives of this study were to evaluate the flavor and taste attributes of
      full-fat Cheddar cheeses with different protein-to-fat ratios (PFR) over aging
      time using a descriptive sensory analysis panel and a consumer panel, and to
      correlate these attributes with instrumental parameters obtained by the
      potentiometric electronic tongue. Three Cheddar cheese formulations (PFR of 0.74,
      0.85, and 1.01) were produced in triplicate and composition was verified. Cheese
      was aged at 7.2 degrees C and evaluated at 2, 5, 8, 10, 11, and 12 mo by a
      trained panel (n = 10) for 8 flavor and 5 taste attributes and using an
      electronic tongue for 7 nonvolatile taste attributes. Cheese aged for 12 mo was
      also evaluated by a consumer sensory panel for liking and intensity attributes.
      Principal component analysis was performed to discriminate cheese based on aging
      time and PFR, whereas correlation between sensory and instrumental attributes was
      assessed using partial least squares regression. Descriptive sensory analysis of
      flavor and taste attributes differentiated Cheddar cheeses over aging time, but
      not among PFR formulations. The electronic tongue distinguished changes among
      cheese samples due to PFR formulation and aging time. The electronic tongue
      proved successful in characterizing the nonvolatile flavor components in Cheddar
      cheese and correlated with taste perceptions measured by descriptive sensory
      analysis. Consumer evaluations showed distinctive attribute profiles for the 3
      PFR Cheddar cheese formulations. Overall, higher fat content was associated with
      increased flavor intensities in Cheddar cheese and drove consumer acceptability
      and purchase intent ratings. The electronic tongue detected smaller changes in
      tastes (bitter, metallic, salty, sour, spicy, sweet, and umami) of the 3 PFR
      formulations over time when compared with the trained panelists, who detected no
      differences, suggesting that the electronic tongue may be more sensitive to
      tastants than humans and may have the capability for early detection or
      identification of problems in a batch of cheese during aging. Results suggest
      taste quality of cheese may be monitored using the electronic tongue with greater
      sensitivity than a trained panel, and may be more objective, rapid, and cost
      effective than human panelists.

PMID- 29331464
TI  - Somatic cell count-based selection reduces susceptibility to energy shortage
      during early lactation in a sheep model.
AB  - During the transition from late gestation to early lactation ruminants experience
      a negative energy balance (NEB), which is considered to increase susceptibility
      to mammary infections. Our previous study in 2 divergent lines of sheep selected
      for high and low somatic cell score (SCS) suggested an association between the
      response to NEB and genetic susceptibility to mastitis. Forty-eight early
      lactation primiparous dairy ewes from the 2 SCS genetic lines were allocated to 2
      homogeneous subgroups-an NEB group, which was energy restricted and received 60%
      of the energy requirements for 15 d, and a control-fed group-to obtain 4 balanced
      groups of 12 ewes: high-SCS positive energy balance, low-SCS positive energy
      balance, high-SCS NEB, and low-SCS NEB. High-SCS ewes showed greater weight loss
      and increased plasmatic concentrations of beta-hydroxybutyrate and nonesterified
      fatty acids than low-SCS ewes when confronted with an induced NEB. The aim of
      this study was to further characterize this interaction by combining
      transcriptomic and phenotypic data with a generalized partial least squares
      discriminant analysis using mixOmics package framework. A preliminary analysis
      using 3 blocks of phenotypes (fatty acids, weight and production, blood
      metabolites) revealed a high correlation between fat-to-protein ratio, beta
      hydroxybutyrate, and nonesterified fatty acids concentrations with milk long
      chain fatty acid yields. These phenotypes allowed good discrimination of the
      energy-restricted high-SCS ewes and confirmed a high level of adipose tissue
      mobilization in this group. A second analysis, which included RNA-seq data,
      revealed high correlations between the long-chain fatty acid yields in milk and
      PDK4, CPT1A, SLC25A20, KLF10, and KLF11 expression, highlighting the relationship
      between mobilization of body reserves and enhanced fatty acids utilization for
      energy production in blood cells. Finally, analysis of milk composition measured
      in 1,025 ewes from the 2 genetic lines over 10 yr confirmed significant higher
      fat-to-protein ratio in high-SCS ewes in early lactation. Altogether, our results
      strongly confirmed a genetic link between susceptibility to mastitis and
      metabolic adaptation to energy shortage. Improving genetic resistance to mastitis
      using SCS should be accompanied by a favorable effect on the response to
      metabolic stress, especially in highly stressful early lactation. Moreover, this
      study suggests that the fat-to-protein ratio could be used as a low-cost tool for
      monitoring energy balance and ketosis during this critical phase of lactation.

PMID- 29331465
TI  - Genome-wide association study for milk infrared wavenumbers.
AB  - Individual wavenumbers of the infrared (IR) spectra of bovine milk have been
      shown to be moderately to highly heritable. The objective of this study was to
      identify genomic regions associated with individual milk IR wavenumbers. This is
      expected to provide information about the genetic background of milk composition
      and give insight in the relation between IR wavenumbers and milk components. For
      this purpose, a genome-wide association study was performed for a selected set of
      50 individual IR wavenumbers measured on 1,748 Dutch Holstein cows. Significant
      associations were detected for 28 of the 50 wavenumbers. In total, 24 genomic
      regions distributed over 16 bovine chromosomes were identified. Major genomic
      regions associated with milk IR wavenumbers were identified on chromosomes 1, 5,
      6, 14, 19, and 20. Most of these regions also showed significant associations
      with fat, protein, or lactose percentage. However, we also identified some new
      regions that were not associated with any one of these routinely collected milk
      composition traits. On chromosome 1, we identified 2 new genomic regions and
      hypothesized that they are related to variation in milk phosphorus content and
      orotic acid, respectively. On chromosome 20, we identified a new genomic region
      that seems to be related to citric acid. Identification of genomic regions
      associated with milk phosphorus content, orotic acid, and citric acid suggest
      that the milk IR spectra contain direct information on these milk components.
      Consequently milk IR analyses probably can be used to predict these milk
      components, which have low concentrations in milk; this can lead to novel
      applications of milk IR spectroscopy for dairy cattle breeding and herd
      management.

PMID- 29331466
TI  - High-grain diets supplemented with phytogenic compounds or autolyzed yeast
      modulate ruminal bacterial community and fermentation in dry cows.
AB  - The feeding of concentrate-rich diets may lead to microbial imbalances and
      dysfermentation in the rumen. The main objective of this study was to determine
      the effects of supplementing phytogenic compounds (PHY) or autolyzed yeast (AY)
      on rumen fermentation and microbial abundance in cows intermittently fed
      concentrate-rich diets. The experiment was carried out as an incomplete 3 * 4
      Latin square design, with 8 nonlactating rumen-fistulated Holstein-Friesian cows.
      The cows were randomly assigned to a concentrate diet that was either not
      supplemented (CON), or supplemented with PHY or AY. Each of the 4 consecutive
      experimental periods was composed of a 1-wk roughage-only diet (RD), 6-d gradual
      concentrate increase, followed by 1 wk of 65% concentrate (dry matter basis; Conc
      I), and 1 wk of RD and a final 2-wk 65% concentrate (dry matter basis; Conc II)
      phase. Digesta samples were collected from the rumen mat for bacterial 16S rRNA
      gene Illumina MiSeq (Illumina, Balgach, Switzerland) sequencing, and samples of
      particle-associated rumen liquid were obtained for measuring short-chain fatty
      acids, lactate, ammonia, and pH during RD (d 6), Conc I (d 19), and Conc II (d
      39). The concentrate feeding caused a decrease of overall bacterial diversity
      indices, especially during Conc I. The genera Ruminococcus, Butyrivibrio, and
      Coprococcus were decreased, whereas Prevotella, Megasphaera, Lachnospira, and
      Bacteroides were increased in abundance. Supplementation of both feed additives
      increased the abundance of gram-positive and decreased that of gram-negative
      bacteria. Supplementation of AY enhanced cellulolytic bacteria such as
      Ruminococcus spp., whereas PHY decreased starch and sugar fermenters including
      Bacteroides spp., Shuttleworthia spp., and Syntrophococcus spp. Moreover, PHY
      supplementation increased butyrate percentage in the rumen in both concentrate
      phases. In conclusion, intermittent high-concentrate feeding altered the digesta
      associated rumen bacterial community and rumen fermentation with more significant
      alterations found in Conc I than in Conc II. The data also showed that both feed
      additives had the most significant modulatory effects on the bacterial community,
      and their subsequent fermentation, during periods of low pH.

PMID- 29331468
TI  - Symposium review: The influences of heat stress on bovine mammary gland function.
AB  - Heat stress reduces cow milk yield and results in a significant economic loss for
      the dairy industry. During lactation, heat stress lowers milk production by 25 to
      40% with half of the decrease in milk synthesis resulting from the reduced feed
      intake. In vitro studies indicate that primary bovine mammary epithelial cells
      display greater rates of programmed cell death when exposed to high ambient
      temperatures, which may lead to a decrease in the total number of mammary
      epithelial cells in the mammary gland, partially explaining the lower milk
      production of lactating cows under heat stress. The function of mammary cells is
      also altered by heat stress. In response to heat stress, mammary cells display
      higher gene expression of heat shock proteins, indicating a need for
      cytoprotection from protein aggregation and degradation. Further, heat stress
      results in increased gene expression without altering protein expression of
      mammary epithelial cell junction proteins, and does not substantially influence
      the integrity of mammary epithelium. These data suggest that the mammary gland
      strives to maintain cell-to-cell junction integrity by synthesizing more proteins
      to compensate for protein losses induced by heat stress. During the dry period,
      heat stress negatively affects mammary gland development by reducing mammary cell
      proliferation before parturition, resulting in a dramatic decrease in milk
      production in the subsequent lactation. In addition to mammary growth, the
      mammary gland of the heat-stressed dry cow has reduced protein expression of
      autophagic proteins in the early dry period, suggesting heat stress influences
      mammary involution. Emerging evidence also indicates that heifers born to cows
      that experience late-gestation heat stress have lower milk yield during their
      first lactation, implying that the maternal environment may alter mammary gland
      development of the offspring. It is not clear if this is due to a direct
      epigenetic modification of prenatal mammary gland development by maternal heat
      stress. More research is needed to elucidate the effect of heat stress on mammary
      gland development and function.

PMID- 29331467
TI  - Canadian National Dairy Study: Herd-level milk quality.
AB  - The objective of this study was to estimate Canadian national milk quality
      parameters and estimate the bulk tank milk (BTM) prevalence of 4 mastitis
      pathogens, Staphylococcus aureus, Streptococcus agalactiae, Mycoplasma bovis, and
      Prototheca spp., on Canadian dairy farms. A questionnaire was sent to all
      Canadian dairy producers. Of the 1,062 producers who completed the questionnaire,
      374 producers from across the country were visited and milking hygiene was
      assessed. Farm-level milk quality data for all Canadian dairy producers was
      collected from the provincial marketing boards and combined with the
      questionnaire and farm visit data. In addition, a BTM sample was collected either
      during the farm visit or by the marketing board in November of 2015 and was
      tested for 4 major mastitis pathogens using the PathoProof Mastitis Major 4 PCR
      Assay (Thermo Fisher Scientific Inc., Waltham, MA). Apparent herd-level
      prevalence was 46% for S. aureus, 6% for Prototheca spp., 0% for M. bovis, and 0%
      for Strep. agalactiae. Due to the low prevalence of M. bovis and Strep.
      agalactiae and a lack of significant factors associated with farms testing
      positive for Prototheca spp., an association analysis could only be carried out
      for Staph. aureus-positive farms. Factors associated with Staph. aureus-positive
      farms were not fore-stripping cows before milking (odds ratio = 1.87), milking
      with a pipeline system (odds ratio = 2.21), and stall bases made of a rubberized
      surface (mats and mattresses), whereas protective factors were using blanket dry
      cow therapy (odds ratio = 0.49) and applying a tag or visible mark on cows known
      to have chronic mastitis infections (odds ratio = 0.45). The Canadian national
      production-weighted geometric mean somatic cell count was determined to be
      208,000 cells/mL. This is the first national dairy study conducted in Canada.
      Participating farms had higher milk yield; were more likely to have a loose
      housing system, parlor, or automated milking system; and had lower weighted mean
      BTM somatic cell count than the national level. Sampling larger farms with better
      milk quality means the apparent prevalence of the 4 mastitis pathogens likely
      underestimates the true levels.

PMID- 29331470
TI  - The effect of different precooling rates and cold storage on milk microbiological
      quality and composition.
AB  - The objective of this study was to measure the effect of different milk cooling
      rates, before entering the bulk tank, on the microbiological load and composition
      of the milk, as well as on energy usage. Three milk precooling treatments were
      applied before milk entered 3 identical bulk milk tanks: no plate cooler (NP),
      single-stage plate cooler (SP), and double-stage plate cooler (DP). These
      precooling treatments cooled the milk to 32.0 +/- 1.4 degrees C, 17.0 +/- 2.8
      degrees C, and 6.0 +/- 1.1 degrees C, respectively. Milk was added to the bulk
      tank twice daily for 72 h, and the tank refrigeration temperature was set at 3
      degrees C. The blend temperature within each bulk tank was reduced after each
      milking event as the volume of milk at 3 degrees C increased simultaneously. The
      bacterial counts of the milk volumes precooled at different rates did not differ
      significantly at 0 h of storage or at 24-h intervals thereafter. After 72 h of
      storage, the total bacterial count of the NP milk was 3.90 +/- 0.09 log10 cfu/mL,
      whereas that of the precooled milk volumes were 3.77 +/- 0.09 (SP) and 3.71 +/-
      0.09 (DP) log10 cfu/mL. The constant storage temperature (3 degrees C) over 72 h
      helped to reduce bacterial growth rates in milk; consequently, milk composition
      was not affected and minimal, if any, proteolysis occurred. The DP treatment had
      the highest energy consumption (17.6 +/- 0.5 Wh/L), followed by the NP (16.8 +/-
      2.7 Wh/L) and SP (10.6 +/- 1.3 Wh/L) treatments. This study suggests that
      bacterial count and composition of milk are minimally affected when milk is
      stored at 3 degrees C for 72 h, regardless of whether the milk is precooled;
      however, milk entering the tank should have good initial microbiological quality.
      Considering the numerical differences between bacterial counts, however, the use
      of the SP or DP precooling systems is recommended to maintain low levels of
      bacterial counts and reduce energy consumption.

PMID- 29331469
TI  - Peroxisome proliferator-activated receptor delta regulates lipid droplet
      formation and transport in goat mammary epithelial cells.
AB  - Even though recent evidence in goat mammary epithelial cells (GMEC) suggest a
      role of peroxisome proliferator-activated receptor delta (PPARD) in regulating
      lipid homeostasis, its role is not fully understood. Our hypothesis was that
      PPARD regulates lipid transport processes in GMEC and, thus, plays a crucial role
      in regulating fat formation. The PPARD was overexpressed using an adenovirus
      system (Ad-PPARD) with recombinant green fluorescent protein (Ad-GFP) as the
      control. Results revealed that overexpression of PPARD markedly upregulated the
      mRNA abundance of PPARD. Compared with the control (Ad-GFP+dimethyl sulfoxide),
      overexpression of PPARD alone had no effect on mRNA expression of CD36, SCD1,
      FABP4, ACSL1, and ADRP. The cultures overexpressing PPARD with the PPARD ligand
      GW0742 (GW) upregulated the expression of CD36, FABP3, FABP4, ACSL1, and ADRP.
      Overexpression of PPARD in GMEC plus GW increased the concentration of 16:1 and
      18:1-trans and was associated with upregulation of SCD1. Compared with the
      control (Ad-GFP+dimethyl sulfoxide), the decrease of triacylglycerol
      concentration coupled with upregulation of genes related to lipid droplet
      secretion (e.g., ADRP and ACSL1) induced by PPARD overexpression suggests a role
      in lipid droplet (LD) secretion. Luciferase assay revealed that GW increased the
      ADRP promoter activity in a dose-dependent manner. Knockdown of PPARD impaired
      the increase of ADRP promoter activity induced by GW, whereas GW enhanced the
      activity of ADRP promoter in GMEC overexpressing PPARD. Data with the ADRP 5'
      flanking truncated luciferase reporter suggest a core region (-1,444 to -990 bp)
      response element for the induction of GW. This core region contains a known PPARG
      response element (PPRE) at -1,003 to -990 bp. When the PPRE was mutated, the
      overexpression of PPARD had no effect on ADRP promoter activity. Collectively,
      these results reveal a novel role for PPARD in lipid homeostasis via promoting
      fatty acid transport and LD formation through a mechanism of direct binding to
      the promoter of key genes. Hence, PPARD activity may contribute to fatty acid
      transport and LD formation during lactation.

PMID- 29331471
TI  - Symposium review: Novel strategies to genetically improve mastitis resistance in
      dairy cattle.
AB  - Mastitis is a disease of major economic importance to the dairy cattle sector
      because of the high incidence of clinical mastitis and prevalence of subclinical
      mastitis and, consequently, the costs associated with treatment, production
      losses, and reduced animal welfare. Disease-recording systems compiling data from
      a large number of farms are still not widely implemented around the world; thus,
      selection for mastitis resistance is often based on genetically correlated
      indicator traits such as somatic cell count (SCC), udder depth, and fore udder
      attachment. However, in the past years, several countries have initiated
      collection systems of clinical mastitis, based on producers recording data in
      most cases. The large data sets generated have enabled researchers to assess
      incidence of this disease and to investigate the genetic background of clinical
      mastitis itself, as well as its relationships with other traits of interest to
      the dairy industry. The genetic correlations between clinical mastitis and its
      previous proxies were estimated more accurately and confirmed the strong
      relationship of clinical mastitis with SCC and udder depth. New traits deriving
      from SCC were also studied, with the most relevant findings being associated with
      mean somatic cell score (SCS) in early lactation, standard deviation of SCS, and
      excessive test-day SCC pattern. Genetic correlations between clinical mastitis
      and other economically important traits indicated that selection for mastitis
      resistance would also improve resistance against other diseases and enhance both
      fertility and longevity. However, milk yield remains negatively correlated with
      clinical mastitis, emphasizing the importance of including health traits in the
      breeding objectives to achieve genetic progress for all important traits. These
      studies enabled the establishment of new genetic and genomic evaluation models,
      which are more efficient for selection to mastitis resistance. Further studies
      that are potential keys for future improvement of mastitis resistance are deep
      investigation of the bacteriology of mastitis, identification of novel indicator
      traits and tools for selection, and development of a larger female reference
      population to improve reliability of genomic evaluations. These cutting-edge
      studies will result in a better understanding of the genetic background of
      mastitis resistance and enable a more accurate phenotyping and genetic selection
      to improve mastitis resistance, and consequently, animal welfare and industry
      profitability.

PMID- 29331472
TI  - Influence of partially demineralized milk proteins on rheological properties and
      microstructure of acid gels.
AB  - Innovative clean label processes employed in the manufacture of acid gels are
      targeted to modify the structure of proteins that contribute to rheological
      properties. In the present study, CO2-treated milk protein concentrate powder
      with 80% protein in dry matter (TMPC80) was mixed with nonfat dry milk (NDM) in
      different ratios for the manufacture of acid gels. Dispersions of NDM and TMPC80
      that provided 100, 90, 70, and 40% of protein from NDM were reconstituted to 4.0%
      (wt/wt) protein and 12.0% (wt/wt) total solids. Dispersions were adjusted to pH
      6.5, followed by heat treatment at 90 degrees C for 10 min. Glucono-delta-lactone
      was added and samples were incubated at 30 degrees C, reaching pH 4.5 +/- 0.05
      after 4 h of incubation. Glucono-delta-lactone levels were adjusted to compensate
      for the lower buffering capacity of samples with higher proportions of TMPC80,
      which is attributable to the depletion of buffering minerals from both the serum
      and micellar phase during preparation of TMPC80. Sodium dodecyl sulfate-PAGE
      analysis indicated a higher amount of caseins in the supernatant of unheated
      suspensions with increasing proportions of CO2-treated TMPC80, attributable to
      the partial disruption of casein micelles in TMPC80. Heat treatment reduced the
      level of whey proteins in the supernatant due to the heat-induced association of
      whey proteins with casein micelles, the extent of which was larger in samples
      containing more micellar casein (i.e., samples with a lower proportion of
      TMPC80). Particle size analysis showed only small differences between nonheated
      and heated dispersions. Gelation pH increased from ~5.1 to ~5.3, and the storage
      modulus of the gels at pH 4.5 increased from ~300 to ~420 Pa when the proportion
      of protein contributed by TMPC80 increased from 0 to 60%. Water-holding capacity
      also increased and gel porosity decreased with increasing proportion of protein
      contributed by TMPC80. The observed gel properties were in line with
      microstructural observations by confocal microscopy, wherein sample gels
      containing increasing levels of TMPC80 exhibited smaller, well-connected
      aggregates with uniform, homogeneous pore sizes. We concluded that TMPC80 can be
      used to partially replace NDM as a protein source to improve rheological and
      water-holding properties in acid gels. The resultant gels also exhibited
      decreased buffering, which can improve the productive capacity of yogurt
      manufacturing plants. Overall, the process can be leveraged to reduce the amount
      of hydrocolloids added to improve yogurt consistency and water-holding capacity,
      thus providing a path to meet consumer expectations of clean label products.

PMID- 29331473
TI  - A Randomized Trial of Itraconazole vs Prednisolone in Acute-Stage Allergic
      Bronchopulmonary Aspergillosis Complicating Asthma.
AB  - OBJECTIVE: Whether itraconazole monotherapy is effective in the acute stage of
      allergic bronchopulmonary aspergillosis (ABPA) remains unknown. The goal of this
      study was to compare the efficacy and safety of itraconazole and prednisolone
      monotherapy in ABPA. METHODS: Treatment-naive subjects with ABPA complicating
      asthma (January 2012 to December 2013) were randomized to receive either oral
      itraconazole or prednisolone for 4 months. The study was not blinded. The primary
      outcomes were proportion of subjects exhibiting a composite response after 6
      weeks, percent decline in IgE after treatment, and numbers of subjects
      experiencing exacerbation. The secondary outcomes included the time to first
      exacerbation, change in lung function, and treatment-related adverse effects.
      RESULTS: A total of 131 subjects (prednisolone group, n = 63; itraconazole group,
      n = 68) were included in the study. The number of subjects exhibiting a composite
      response was significantly higher in the prednisolone group compared with the
      itraconazole group (100% vs 88%; P = .007). The percent decline in IgE after 6
      weeks and 3 months and the number of subjects with exacerbations after 1 and 2
      years of treatment were similar in the two groups. The time to first exacerbation
      (mean: 437 vs 442 days) and the improvement in lung function after 6 weeks was
      also similar in the two groups. The occurrence of side effects was significantly
      higher in the glucocorticoid arm (P < .001). CONCLUSIONS: Prednisolone was more
      effective in inducing response than itraconazole in acute-stage ABPA. However,
      itraconazole was also effective in a considerable number and, with fewer side
      effects compared with prednisolone, remains an attractive alternative in the
      initial treatment of ABPA. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01321827;
      URL: www.clinicaltrials.gov).

PMID- 29331474
TI  - Clinical Databases for Chest Physicians.
AB  - A clinical database is a repository of patient medical and sociodemographic
      information focused on one or more specific health condition or exposure.
      Although clinical databases may be used for research purposes, their primary goal
      is to collect and track patient data for quality improvement, quality assurance,
      and/or actual clinical management. This article aims to provide an introduction
      and practical advice on the development of small-scale clinical databases for
      chest physicians and practice groups. Through example projects, we discuss the
      pros and cons of available technical platforms, including Microsoft Excel and
      Access, relational database management systems such as Oracle and PostgreSQL, and
      Research Electronic Data Capture. We consider approaches to deciding the base
      unit of data collection, creating consensus around variable definitions, and
      structuring routine clinical care to complement database aims. We conclude with
      an overview of regulatory and security considerations for clinical databases.

PMID- 29331475
TI  - End-of-Life Care for Patients With Advanced Kidney Disease in the US Veterans
      Affairs Health Care System, 2000-2011.
AB  - BACKGROUND: Little is known about patterns of end-of-life care for patients with
      advanced kidney disease not treated with maintenance dialysis. STUDY DESIGN: Case
      series. SETTING & PARTICIPANTS: A sample of 14,071 patients with sustained
      estimated glomerular filtration rates < 15mL/min/1.73m2 treated in the US
      Veterans Affairs health care system who died during 2000 to 2011. Before death,
      12,756 of these patients had been treated with dialysis, 503 had been discussing
      and/or preparing for dialysis therapy, and for 812, there had been a decision not
      to pursue dialysis therapy. OUTCOMES: Hospitalization and receipt of an intensive
      procedure during the final month of life, in-hospital death, and palliative care
      consultation and hospice enrollment before death. RESULTS: Compared with
      decedents treated with dialysis, those for whom a decision not to pursue dialysis
      therapy had been made were less often hospitalized (57.3% vs 76.8%; OR, 0.40 [95%
      CI, 0.34-0.46]), less often the recipient of an intensive procedure (3.5% vs
      24.6%; OR, 0.15 [95% CI, 0.10-0.22]), more often the recipient of a palliative
      care consultation (52.6% vs 21.6%; OR, 4.19 [95% CI, 3.58-4.90]), more often used
      hospice services (38.7% vs 18.2%; OR, 3.32 [95% CI, 2.83-3.89]), and died less
      frequently in a hospital (41.4% vs 57.3%; OR, 0.78 [95% CI, 0.74-0.82]).
      Hospitalization (55.5%; OR, 0.39 [95% CI, 0.32-0.46]), receipt of an intensive
      procedure (13.7%; OR, 0.60 [95% CI, 0.46-0.77]), and in-hospital death (39.0%;
      OR, 0.47 [95% CI, 0.39-0.56]) were also less common among decedents who had been
      discussing and/or preparing for dialysis therapy, but their use of palliative
      care and hospice services was similar. LIMITATIONS: Findings may not be
      generalizable to groups not well represented in the Veterans Affairs health care
      system. CONCLUSIONS: Among decedents, patients not treated with dialysis before
      death received less intensive patterns of end-of-life care than those treated
      with dialysis. Decedents for whom there had been a decision not to pursue
      dialysis therapy before death were more likely to receive palliative care and
      hospice.

PMID- 29331476
TI  - Factors Associated With Withdrawal From Maintenance Dialysis: A Case-Control
      Analysis.
AB  - BACKGROUND: Little is known about differences in the clinical course between
      patients receiving maintenance dialysis who do and do not withdraw from dialysis
      therapy. STUDY DESIGN: Case-control analysis. SETTING & PARTICIPANTS: US patients
      with Medicare coverage who received maintenance hemodialysis for 1 year or longer
      in 2008 through 2011. PREDICTORS: Comorbid conditions, hospitalizations, skilled
      nursing facility stays, and a morbidity score based on durable medical equipment
      claims. OUTCOME: Withdrawal from dialysis therapy. MEASUREMENTS: Rates of medical
      events, hospitalizations, skilled nursing facility stays, and a morbidity score.
      RESULTS: The analysis included 18,367 (7.7%) patients who withdrew and 220,443
      (92.3%) who did not. Patients who withdrew were older (mean age, 75.3+/-11.5 [SD]
      vs 66.2+/-14.1 years) and more likely to be women and of white race, and had
      higher comorbid condition burdens. The odds of withdrawal among women were 7%
      (95% CI, 4%-11%) higher than among men. Compared to age 65 to 74 years, age 85
      years or older was associated with higher adjusted odds of withdrawal (adjusted
      OR, 1.61; 95% CI, 1.54-1.68), and age 18 to 44 years with lower adjusted odds
      (adjusted OR, 0.36; 95% CI, 0.32-0.40). Blacks, Asians, and Hispanics were less
      likely to withdraw than whites (adjusted ORs of 0.36 [95% CI, 0.35-0.38], 0.47
      [95% CI, 0.42-0.53], and 0.46 [95% CI, 0.44-0.49], respectively). A higher
      durable medical equipment claims-based morbidity score was associated with
      withdrawal, even after adjustment for traditional comorbid conditions and
      hospitalization; compared to a score of 0 (lowest presumed morbidity), adjusted
      ORs of withdrawal were 3.48 (95% CI, 3.29-3.67) for a score of 3 to 4 and 12.10
      (95% CI, 11.37-12.87) for a score >=7. Rates of medical events and
      institutionalization tended to increase in the months preceding withdrawal, as
      did morbidity score. LIMITATIONS: Results may not be generalizable beyond US
      Medicare patients; people who withdrew less than 1 year after dialysis therapy
      initiation were not studied. CONCLUSIONS: Women, older patients, and those of
      white race were more likely to withdraw from dialysis therapy. The period before
      withdrawal was characterized by higher rates of medical events and higher levels
      of morbidity.

PMID- 29331477
TI  - Atypical Presentation of Pregnancy-Related Hemolytic Uremic Syndrome.
AB  - The cause of acute kidney injury during pregnancy and in the postpartum period
      can be particularly challenging to diagnose, especially when it is necessary to
      differentiate among preeclampsia; eclampsia; hemolysis, elevated liver enzymes
      and low platelets (HELLP) syndrome; and thrombotic microangiopathies (TMAs). All
      these disease entities can present with kidney failure, microangiopathic
      hemolytic anemia, and thrombocytopenia. We present a teaching case of atypical
      hemolytic uremic syndrome in the postpartum period in a young woman who was found
      to have mutations of uncertain clinical significance in the complement cascade,
      including in C3, CFH, and CFI. We use this as an opportunity to review the
      clinical presentation and pathophysiology of preeclampsia, eclampsia, and the
      TMAs. We focus on diagnostic challenges, especially because many patients with
      TMA do not present with thrombocytopenia, which can delay diagnosis. We
      additionally review the clinical settings in which administration of eculizumab,
      a C5 membrane attack complex inhibitor, is appropriate.

PMID- 29331478
TI  - Comprehensive analysis of lncRNAs and mRNAs with associated co-expression and
      ceRNA networks in C2C12 myoblasts and myotubes.
AB  - Long non-coding RNAs (lncRNAs) are emerging as important regulators in the
      modulation of muscle development and muscle-related diseases. To explore
      potential regulators of muscle differentiation, we determined the expression
      profiles of lncRNAs and mRNAs in C2C12 mouse myoblast cell line using microarray
      analysis. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway
      enrichment analyses were performed to explore their function. We also constructed
      co-expression, cis/trans-regulation, and competing endogenous RNA (ceRNA)
      networks with bioinformatics methods. We found that 3067 lncRNAs and 3235 mRNAs
      were differentially regulated (fold change >=2.0). Bioinformatics analysis
      indicated that the principal functions of the transcripts were related to muscle
      structure development and morphogenesis. Co-expression analysis showed 261 co
      expression relationships between 233 lncRNAs and 10 mRNAs, and nine lncRNAs
      interacted with myog and MEF2C collectively. Cis/trans-regulation prediction
      revealed that lncRNA Myh6 could be a valuable gene via cis-regulation, and
      lncRNAs such as 2310043L19Ris, V00821, and AK139352 may participate in particular
      pathways regulated by transcription factors, including myog, myod1, and foxo1.
      The myog-specific ceRNA network covered 10 lncRNAs, 378 miRNAs, and 1960 edges.
      The upregulated lncRNAs Filip1, Myl1, and 2310043L19Rik may promote myog
      expression by acting as ceRNAs. Our results offer a new perspective on the
      modulation of lncRNAs in muscle differentiation.

PMID- 29331479
TI  - Molecular characterization and expression of Piwil1 and Piwil2 during gonadal
      development and treatment with HCG and LHRH-A2 in Odontobutis potamophila.
AB  - Piwi proteins play an important regulatory role in germ cell division during
      gametogenesis and gonad development. In order to understand the function of Piwi
      genes in the reproductive process of the dark sleeper, we identified and
      characterized Piwil1 and Piwil2 from gonad tissue. The tissue distribution
      demonstrated that Piwils were highly expressed in the gonad of the dark sleeper.
      During gonad development, higher expression was observed in stage I of both the
      testes and ovaries than in subsequent stages at mRNA and protein levels. The
      results of immunohistochemistry demonstrated that Piwils were predominantly
      distributed in the spermatogonia, spermatocytes, and early oocytes. When treated
      with the HPG axis hormone (HCG and LHRH-A2), the expression of Piwils was
      significantly decreased in the testes and ovaries at mRNA and protein levels. All
      of these results indicated that Piwils play a vital role in gonad development and
      gametogenesis. Our findings provide valuable evidence to further clarify the
      underlying modulation mechanism of Piwils in teleosts.

PMID- 29331480
TI  - Human papillomavirus (HPV) 18 genetic variants and cervical cancer risk in
      Taizhou area, China.
AB  - Human papillomavirus (HPV) type 18 is predominantly associated with the
      development of cervical adenocarcinomas, whereas data on HPV18 genetic
      variability in China are limited. HPV18 genetic variants were formed phylogenetic
      tree, including lineages A, B, and C. We aimed to evaluate the diversity of HPV18
      genetic variants by sequencing the entire E6, E7 and L1 genes. Between 2012 and
      2015, a total of 138 (0.8%, 138/17669) women with single HPV18 infection were
      selected in this study. Finally, we observed 122 HPV18 isolates of the complete
      E6-E7-L1 sequences, and obtained 36 distinct variation patterns which the
      accession GenBank numbers as KY457805-KY457840. Except KY457805, KY457813,
      KY457819, KY457827, KY457829, the rest of HPV18 isolates (81.1%, 31/36) are novel
      variants. All of HPV18 variants belong to lineage A, while no lineage B, and C
      was found in our population of Taizhou region, Southeast China. Sublineage A1 was
      the most common variants (85.2%, 104/122), followed by sublineage A4, A3 and A5,
      while no sublineage A2 was obtained. Based on the tree topologies, there were
      three newly identified candidates' sublineages A6-A8. Out of 122 women, 67
      (54.9%) had diagnosed by biopsy, including 49 women who diagnosed with
      cervicitis, 12 with cervical intraepithelial neoplasia (CIN)1, 4 with CIN2/3, and
      2 with adenocarcinomas, respectively. Nevertheless, there was no association
      between HPV18 (sub) lineages and CIN1 or worse (CIN1+) lesions comparing with
      normal biopsies (P = .469). In conclusion, knowledge of the distribution of
      geographic/ethnical HPV18 genetic diversity provides critical information for
      developing diagnostic probes, epidemiologic correlate of cervical cancer risk and
      design of HPV vaccines for targeted populations.

PMID- 29331481
TI  - Genetic contribution of SUN5 mutations to acephalic spermatozoa in Fujian China.
AB  - Acephalic spermatozoa is an extremely rare disease associated with primary
      infertility. A recent study showed that genetic alterations in the SUN5 gene lead
      to this disease, and SUN5 mutations could explain the disease in about half of
      the patients. Therefore, in the present study, to re-visit the genetic
      contribution of SUN5 mutations to acephalic spermatozoa, we recruited 15
      unrelated affected individuals and screened the SUN5 gene for mutations by whole
      exome sequencing (WES) and Sanger sequencing. Five of the 15 (33.33%) subjects
      were found to carry the same homozygous mutation in the SUN5 gene c.381delA
      (p.V128Sfs*7). Neither homozygous nor compound heterozygous mutations in SUN5
      were found in the other 10 patients. The c.381delA mutation resulted in the
      truncation of the SUN5 protein and decreased the expression and altered the
      distribution of the outer dense fiber 1 (ODF1) protein. Thus, in our study SUN5
      mutations accounted for only one-third of the patients in our cohort, which is
      lower than the percentage reported previously. Thus, our study suggests that the
      contribution of SUN5 mutations to acephalic spermatozoa might not be as high as
      described previously. These results will help in the genetic counseling of
      patients with acephalic spermatozoa.

PMID- 29331483
TI  - GATA4 is a transcriptional regulator of R-spondin1 in Japanese flounder
      (Paralichthys olivaceus).
AB  - GATA4 is a well-known transcription factor of the GATA family implicated in
      regulation of sex determination and gonadal development in mammals. In this
      study, we cloned the full-length cDNA of Paralichthys olivaceus gata4 (Po-gata4).
      Phylogenetic, gene structure, and synteny analysis showed that Po-GATA4 is
      homologous to GATA4 of teleost and tetrapod. Po-gata4 transcripts were detected
      in Sertoli cells, spermatogonia, oogonia and oocytes, with higher transcript
      levels overall in the testis than the ovary. The promoter region of P. olivaceus
      R-spondin1was found to contain a GATA4-binding motif. Results of CBA (cleaved
      amplified polymorphic sequence-based binding assay) indicated that GATA4 could
      indeed bind to the promoter sequence of R-spondin1. Moreover, human GATA4
      recombinant protein could upregulate R-spondin1 in P. olivaceus ovary cells and
      FBCs (flounder brain cell line). In FBCs, overexpression of Po-gata4 resulted in
      elevated transcript levels of R-spondin1. Taken together, our results indicate
      that Po-GATA4 is involved in gonadal development by regulating R-spondin1
      expression.

PMID- 29331484
TI  - Novel biomolecular information in rotenone-induced cellular model of Parkinson's
      disease.
AB  - In order to uncover the remarkable pathogenic genes or molecular pathological
      process in Parkinson's disease (PD), we employed a microarray analysis upon the
      cellular PD model induced by rotenone. Compared to the control group, 2174 genes
      were screened out to be expressed differently in the rotenone-induced group by
      certain criterion. GO analysis and the pathways analysis showed the significant
      enrichment of genes that were associated with the biological process of cell
      cycle, apoptotic process, organelle fusion, mitochondrial lesion, endoplasmic
      reticulum stress and so on. Among these significant DE genes, some were sorted
      out to be involved in cell cycle and protein processing in endoplasmic reticulum.
      As the PPI network analysis showed, the interaction relationship of the DEGs
      involved in the process of protein generation in endoplasmic reticulum(ER) was
      clearly showed up. As a prediction, we emphasized the genes EDEM1, ATF4, TRAF2
      might play central roles in the protein misfolding process during the progression
      of Parkinson's disease and these new-found genes might be the future research
      focus and therapeutic targets in PD.

PMID- 29331485
TI  - Impact of 9p21.3 region and atherosclerosis-related genes' variants on long-term
      recurrent hard cardiac events after a myocardial infarction.
AB  - Atherosclerotic coronary artery disease (CAD) and myocardial infarction (MI) as
      its most severe clinical complication remain the leading causes of mortality in
      the majority of countries. Despite the progress in the treatment of MI, quite
      often the patients, after the first-time MI, develop subsequently a variety of
      adverse cardiovascular events. In this retrospective study we evaluated the
      contribution of allelic variations in 9p21.3 locus and in 21 atherogenesis
      related genes to the development of hard cardiac events in a cohort of patients
      of Russian ethnicity after the first acute MI during long-term follow-up (7-10
      years). Death from cardiac causes and recurrent nonfatal MI were considered as
      key clinical outcomes. We have shown the association of rs1333049 and rs10757278
      in 9p21.3 and MTHFR rs1801133 with recurrent unfavorable events, the latter was
      observed in time-dependent manner. Multilocus analysis additionally suggested the
      influence of carriage of the CRP and ENOS genes variants at the development of
      subsequent adverse events after MI. The composite model built for prediction of
      the individual genetic risk of postinfarction hard cardiac events included 9p21.3
      rs1333049*GG and MTHFR*TT and was characterized by area under the curve (AUC) =
      0.65. Our data show that 9p21.3 locus and MTHFR gene polymorphisms could
      influence long-term prognosis of recurrent hard cardiac events in patients who
      underwent the first MI. It is possible that addition of genotyping at such loci
      to existing clinical scores could improve their predictability.

PMID- 29331482
TI  - Genetic basis of hearing loss in Spanish, Hispanic and Latino populations.
AB  - Hearing loss (HL) is the most common neurosensory disorder affecting humans. The
      screening, prevention and treatment of HL require a better understanding of the
      underlying molecular mechanisms. Genetic predisposition is one of the most common
      factors that leads to HL. Most HL studies include few Spanish, Hispanic and
      Latino participants, leaving a critical gap in our understanding about the
      prevalence, impact, unmet health care needs, and genetic factors associated with
      hearing impairment among Spanish, Hispanic and Latino populations. The few
      studies which have been performed show that the gene variants commonly associated
      with HL in non-Spanish and non-Hispanic populations are infrequently responsible
      for hearing impairment in Spanish as well as Hispanic and Latino populations
      (hereafter referred to as Hispanic). To design effective screening tools to
      detect HL in Spanish and Hispanic populations, studies must be conducted to
      determine the gene variants that are most commonly associated with hearing
      impairment in this racial/ethnic group. In this review article, we summarize gene
      variants and loci associated with HL in Spanish and Hispanic populations.
      Identifying new genetic variants associated with HL in Spanish and Hispanic
      populations will pave the way to develop effective screening tools and
      therapeutic strategies for HL.

PMID- 29331486
TI  - Prenatal exposure to acetaminophen and children's language development at 30
      months.
AB  - OBJECTIVE: To examine prenatal APAP exposure in relation to language development
      in offspring at 30 months of age. METHOD: A population-based pregnancy cohort
      study including 754 women who enrolled in the Swedish Environmental Longitudinal,
      Mother and child, Asthma and allergy (SELMA) study in pregnancy week 8-13. Two
      exposure measures were used: (1) maternally reported number of APAP tablets taken
      between conception and enrollment; (2) APAP urinary concentration at enrollment.
      Language development at 30 months was assessed by nurse's evaluation and parental
      questionnaire, including the number of words the child used (<25, 25-50 and >50).
      Main study outcome; parental report of use of fewer than 50 words, termed
      language delay (LD). RESULTS: 59.2% of women enrolled in weeks 8-13 reported
      taking APAP between conception and enrollment. APAP was measurable in all urine
      samples and urinary APAP was correlated with the number of APAP taken during
      pregnancy (P<0.01). Language delay was more prevalent in boys (12.6%) than girls
      (4.1%) (8.5% in total). Both the number of APAP tablets and urinary APAP
      concentration were associated with greater LD in girls but not in boys. The
      adjusted odds ratio (OR) for LD among girls whose mothers reported >6 vs. 0 APAP
      tablets was 5.92 (95% confidence interval (CI) 1.10-31.94). The OR for LD in
      girls whose mothers' urinary APAP was in the highest compared to the lowest
      quartile was 10.34 (95% CI 1.37-77.86). While it cannot be ruled out, our
      available data do not support confounding by indication. CONCLUSIONS: Given the
      prevalence of prenatal APAP use and the importance of language development, these
      findings, if replicated, would suggest that pregnant women should limit their use
      of this analgesic during pregnancy.

PMID- 29331487
TI  - CureCuma-cationic curcuminoids with improved properties and enhanced
      antimicrobial photodynamic activity.
AB  - The naturally occurring photosensitizer curcumin has excellent biocompatibility,
      but its antimicrobial photodynamic efficacy is limited by (i) weak adherence to
      Gram(-) bacteria cell walls, (ii) low (photo-)stability and (iii) limited
      solubility in water. In this study novel curcuminoids bearing cationic
      substituents were prepared by different synthetic routes. The derivatives exhibit
      excellent water solubility, improved photostability and low aggregation. All
      novel curcuminoids showed antibacterial photodynamic effects (>3 log10 reduction
      of CFU) against Escherichia coli and Staphylococcus aureus upon blue light
      illumination. In contrast to natural curcumin, effective photokilling of E. coli
      was possible without the addition of permeabilizing agents. Ten micromolar of the
      most active compound (8) achieved a 7 log10 decrease of E. coli after light
      activation with a fluence of 33.8 J/cm2, whereas S. aureus was inactivated by
      more than 4 log10 at a fluence of 5.3 J/cm2. Overall the reduction in bacterial
      count was at least 100-fold more effective with these new curcuminoids in
      comparison to natural curcumin.

PMID- 29331488
TI  - A potential utilization of end-of-life tyres as recycled carbon black in EPDM
      rubber.
AB  - End-of-life (EOL) tyres and their decomposition present severe environmental
      concern due to their resistance to moisture, oxygen, natural degradation, etc.
      Pyrolysis is considered to be the most effective and sustainable process for
      recycling, due to its eco-friendly process. The current work studied the effect
      of recycled carbon black (rCB), obtained from the pyrolysis of EOL tyres, on the
      properties of ethylene propylene diene rubber (EPDM). The rCB was characterized
      by scanning electron microscopy (SEM), thermogravimetric analysis (TGA) and
      chemical methods. rCB was incorporated solely, into a conventional EPDM
      formulation and also in combination with N550 carbon black. The physico
      mechanical properties of the EPDM vulcanizates, before and after aging, were
      succinctly studied by SEM, TGA, Differential Scanning Calorimetry (DSC), tensile
      tests and cross-link density. The average particle size of rCB was observed to be
      8 um and the ash content was observed to be higher when compared to the
      conventional N550 carbon black, which was evident, by the TGA and SEM-EDX
      analyses. The reinforcing effect and the cross-link density of the rCB-filled
      vulcanizates were found to be marginally inferior in comparison to the
      conventional carbon black (N550). The morphology of the tensile- and tear
      fractured surfaces were studied by SEM and it was observed that the breaking
      mechanism follows the rubber chain detachment from the surface mode.

PMID- 29331489
TI  - Modulation of lower extremity joint stiffness, work and power at different
      walking and running speeds.
AB  - Locomotion task and speed changes affect dynamic joint function. Walking and
      running require different coordination patterns of lower extremity joint
      mechanics. These coordination differences can result in measurable changes in
      kinematic and kinetic patterns. When locomotion speed changes, the functional
      role and movement strategy of each joint is altered. A deeper understanding of
      joint level mechanics and functional interactions will benefit rehabilitation
      programs and assistive device development. In this study, joint stiffness, joint
      mechanical work and power were assessed, as they relate to dynamic function of
      joints during locomotion. Ten young healthy subjects (5 males, 5 females)
      participated in a treadmill walking (0.8-2.0 m/s) and running (1.8-3.8 m/s)
      study. When running speed increased, the stiffness of all three joints tended to
      increase. The ankle joint played a dominant role during the stance phase of
      running, generating more positive work than the knee (p = .003) and hip (p =
      .0001). The knee and hip joint were more dominant in walking and running swing
      phase energy absorption and generation, respectively. When locomotion speeds
      increased, stance phase ankle positive work, swing phase knee negative work, and
      hip joint positive work tended to increase. These findings suggest that change of
      locomotion speed or task results in definitive changes to lower extremity joint
      level mechanics patterns.

PMID- 29331490
TI  - Supervised Machine Learning for Population Genetics: A New Paradigm.
AB  - As population genomic datasets grow in size, researchers are faced with the
      daunting task of making sense of a flood of information. To keep pace with this
      explosion of data, computational methodologies for population genetic inference
      are rapidly being developed to best utilize genomic sequence data. In this review
      we discuss a new paradigm that has emerged in computational population genomics:
      that of supervised machine learning (ML). We review the fundamentals of ML,
      discuss recent applications of supervised ML to population genetics that
      outperform competing methods, and describe promising future directions in this
      area. Ultimately, we argue that supervised ML is an important and underutilized
      tool that has considerable potential for the world of evolutionary genomics.

PMID- 29331491
TI  - Investigating the relationship between cardiac interoception and autonomic
      cardiac control using a predictive coding framework.
AB  - Predictive coding models, such as the 'free-energy principle' (FEP), have
      recently been discussed in relation to how interoceptive (afferent visceral
      feedback) signals update predictions about the state of the body, thereby driving
      autonomic mediation of homeostasis. This study appealed to 'interoceptive
      inference', under the FEP, to seek new insights into autonomic (dys)function and
      brain-body integration by examining the relationship between cardiac
      interoception and autonomic cardiac control in healthy controls and patients with
      forms of orthostatic intolerance (OI); to (i) seek empirical support for
      interoceptive inference and (ii) delineate if this relationship was sensitive to
      increased interoceptive prediction error in OI patients during head-up tilt
      (HUT)/symptom provocation. Measures of interoception and heart rate variability
      (HRV) were recorded whilst supine and during HUT in healthy controls (N = 20),
      postural tachycardia syndrome (PoTS, N = 20) and vasovagal syncope (VVS, N = 20)
      patients. Compared to controls, interoceptive accuracy was reduced in both OI
      groups. Healthy controls' interoceptive sensibility positively correlated with
      HRV whilst supine. Conversely, both OI groups' interoceptive awareness negatively
      correlated with HRV during HUT. Our pilot study offers initial support for
      interoceptive inference and suggests OI cohorts share a central pathophysiology
      underlying interoceptive deficits expressed across distinct cardiovascular
      autonomic pathophysiology. From a predictive coding perspective, OI patients'
      data indicates a failure to attenuate/modulate ascending interoceptive prediction
      errors, reinforced by the concomitant failure to engage autonomic reflexes during
      HUT. Our findings offer a potential framework for conceptualising how the human
      nervous system maintains homeostasis and how both central and autonomic processes
      are ultimately implicated in dysautonomia.

PMID- 29331492
TI  - Prognostic Value of the Expression of DNA Repair-Related Biomarkers Mediated by
      Alcohol in Gastric Cancer Patients.
AB  - Alcohol consumption likely induces gastric carcinogenesis through deregulation of
      RNA polymerase (Pol) III genes and oxidative damage. Transcription factor IIB
      related factor 1 (BRF1) overexpression alleviates RNA Pol III transcription
      inhibition through breast cancer susceptibility gene 1 (BRCA1). Myeloperoxidase
      (MPO) involvement in cancer is induced by alcohol-mediated oxidative damage.
      BRCA1/2 and MPO play key roles in DNA repair. BRCA1 and BRCA2 exert different
      roles in homologous recombination repair. By using human gastric cancer (GC)
      biopsies, we investigated the prognostic value of these proteins upon alcohol
      induction. In total, high expression of BRF1 (P = 0.010) and positive cell
      infiltration of MPO (P = 0.004) in tumor tissues as well as positive expression
      of BRCA1 (P < 0.001) in para-tumor tissues were more frequent in GC patients with
      hazardous or harmful alcohol consumption habits. BRF1 (P = 0.021), BRCA2 (P <
      0.001), and MPO (P = 0.039) were independent prognostic factors for disease-free
      survival. BRCA1 (P = 0.005) and BRCA2 (P < 0.001) also were identified as
      independent prognostic factors for overall survival. Furthermore, BRCA2 was an
      independent unfavorable prognostic factor for disease-free survival and overall
      survival (P < 0.001) in GC patients who underwent platinum-based adjuvant
      chemotherapy. BRF1, BRCA1/2, and MPO are DNA repair-related biomarkers, induced
      by alcohol with prognostic value in GC patients.

PMID- 29331493
TI  - Hip Dislocations in the Emergency Department: A Review of Reduction Techniques.
AB  - BACKGROUND: Hip dislocations are a common presentation in the Emergency
      Department (ED) and require urgent reduction to reduce the risk of avascular
      necrosis. Over 90% of all dislocations can successfully be reduced in the ED and
      there is evidence that cases awaiting operative reduction result in significant
      delays. DISCUSSION: While there is limited data comparing specific techniques,
      the individual success rates of most maneuvers range from 60-90%. Additionally,
      each technique has distinct advantages and limitations associated with its use.
      CONCLUSIONS: It is important for Emergency Physicians to be familiar with several
      different reduction techniques in case the initial reduction attempt is
      unsuccessful or patient characteristics limit the use of certain maneuvers. This
      article reviews a number of reduction techniques for hip dislocations, variations
      on these techniques, and advantages and disadvantages for each approach.

PMID- 29331494
TI  - A Novel Difficult-Airway Prediction Tool for Emergency Airway Management:
      Validation of the HEAVEN Criteria in a Large Air Medical Cohort.
AB  - BACKGROUND: Difficult-airway prediction tools help identify optimal airway
      techniques, but were derived in elective surgery patients and may not be
      applicable to emergency rapid sequence intubation (RSI). The HEAVEN criteria
      (Hypoxemia, Extremes of size, Anatomic abnormalities, Vomit/blood/fluid,
      Exsanguination, Neck mobility issues) may be more relevant to emergency RSI
      patients. OBJECTIVE: To validate the HEAVEN criteria for difficult-airway
      prediction in emergency RSI using a large air medical cohort. METHODS: This was a
      retrospective analysis using a large air medical airway registry using data from
      160 bases over a 1-year period. Standard test characteristics (sensitivity,
      specificity, positive predictive value, negative predictive value [NPV]) for the
      HEAVEN criteria were calculated for overall intubation success, first-attempt
      success, and first-attempt success without desaturation. In addition,
      multivariable logistic regression was used to quantify the independent
      association between each of the HEAVEN criteria, as well as the total number of
      criteria present and intubation success after adjusting for age, gender, and
      clinical category (burn, medical, trauma, nontraumatic shock). RESULTS: A total
      of 2419 patients undergoing air medical RSI were included. Excellent NPV was
      observed (97% for each of the HEAVEN criteria except "Exsanguination," which had
      an NPV of 87% but specificity of 99%). First-attempt success was lower for each
      of the HEAVEN criteria, with an inverse relationship observed between total
      HEAVEN criteria and intubation success (first-attempt success with no criteria =
      94% and with 5 + criteria = 43%). Multivariable logistic regression revealed
      independent associations between each of the HEAVEN criteria, as well as total
      number of criteria and intubation success. CONCLUSIONS: The HEAVEN criteria seem
      to be a useful tool to predict difficult airways in emergency RSI.

PMID- 29331495
TI  - Role of BCL2L10 in regulating buffalo (Bubalus bubalis) oocyte maturation.
AB  - It has been reported that BCL2L10 is abundantly and specifically expressed in
      adult human and mouse oocytes and played a very important role in oocytes
      maturation and early embryonic development. This study is to investigate the
      expression pattern of BCL2L10 in buffalo ovaries and its effect on the in vitro
      maturation of buffalo oocytes, so as to dissect mechanism of oocytes maturation
      and provide theoretical guidance for improvement of the in vitro maturation of
      buffalo oocytes. The results showed that BCL2L10 gene was enriched in ovary and
      the expression of BCL2L10 was oocyte specific and up-regulated during oocyte
      maturation. BCL2L10 protein and mRNA were detectable in buffalo early embryos,
      upregulated at 2-cell to 8-cell stages and down-regulated in the later stages.
      Knockdown of BCL2L10 by RNA interference resulted in a significant decrease in
      the maturation rate (33.5%) and cleavage rate (37.52%) of buffalo oocytes coupled
      with up-regulation of apoptosis-related gene Caspase-9. We concluded that BCL2L10
      is a candidate associated with buffalo oocyte maturation.

PMID- 29331496
TI  - Maternal betaine supplementation attenuates glucocorticoid-induced hepatic lipid
      accumulation through epigenetic modification in adult offspring rats.
AB  - There are lots of reports about alleviation of NAFLD by dietary supplements of
      betaine. However, it remains unclear whether maternal betaine supplementation can
      also ameliorate NAFLD in offspring. Hence, twenty pregnant rats were fed with a
      basal diet with or without betaine (1%), and then the female offspring rats were
      raised at 3 months of age followed by 3 weeks of physiological saline or
      dexamethasone in a dose of 0.1 mg/kg body mass every day via intraperitoneal
      injection. In this study, maternal betaine supplementation significantly (P<.05)
      reduced the increase of hepatic triglycerides concentration in dexamethasone
      induced rats, which is associated with the expression of hepatic lipogenic genes
      (ACC1, FASN and SCD1). Moreover, the hypomethylation of lipogenic genes in
      dexamethasone-induced rats were reserved by prenatal betaine exposure.
      Furthermore, the increase of hepatic GR or SP1 content in dexamethasone-injected
      rats were significantly decreased (P<.05), which were in line with the binding of
      GR or SP1 to lipogenic genes, in betaine -exposed rats. Together, these results
      suggest that maternal betaine supplementation attenuates dexamethason-induced
      fatty liver in the female adult offspring rats, which may be attributed to DNA
      methylation and GR or SP1-mediated the regulation of lipogenic genes.

PMID- 29331497
TI  - Dietary antioxidant micronutrients alter mucosal inflammatory risk in a murine
      model of genetic and microbial susceptibility.
AB  - Inflammatory bowel diseases (IBD) are caused by the convergence of microbial,
      environmental, and genetic factors. Diet significantly alters these interactions
      by affecting both the host and microbiome. Using a mucosal inflammatory model
      that resembles the human condition of ileal pouchitis, we investigated the
      effects of Control (CONT) or Antioxidant (AOX) diet, containing pharmacologically
      relevant levels of 4 micronutrients, on disease risk in wild-type and IL-10-/-
      animals following surgical self-filling (SF) ileal blind loop placement. Although
      no differences were found in body weight change or survival, IL-10-/- CONT
      animals had significantly larger lymphoid organs compared with IL-10-/- AOX or
      with WT. SF loops from IL-10-/- CONT loop mucosa demonstrated histological
      inflammation, characterized by goblet cell depletion, increased mucosal
      myeloperoxidase (MPO), and elevated IFNgamma, TNFalpha, and IL-17alpha gene
      expression, which AOX attenuated. AOX elevated luminal IgA in IL-10-/- animals,
      but not significantly in WT. In IL-10-/- animals, AOX significantly decreased the
      percentage of CD4 + T-bet and CD4 + RORgamma T-cells compared with CONT, with no
      changes in CD4 + Foxp3+ Treg cells. 16S rRNA gene sequencing demonstrated AOX
      increased microbial alpha diversity compared with CONT in both genotypes.
      Notably, colonizing germ-free IL-10-/- hosts with CONT bacterial communities, but
      not AOX, recapitulated the inflammatory phenotype. Collectively, these findings
      highlight that common dietary antioxidant micronutrients reshape the gut
      microbial community to mitigate intestinal inflammatory profiles in genetically
      susceptible hosts. Insights into the dietary-immune-microbial nexus may improve
      understanding for recurrent inflammatory episodes in susceptible patient
      populations and opportunities for practical therapeutics to restore immune and
      microbial homeostasis.

PMID- 29331498
TI  - Identification of neural transcription factors required for the differentiation
      of three neuronal subtypes in the sea urchin embryo.
AB  - Correct patterning of the nervous system is essential for an organism's survival
      and complex behavior. Embryologists have used the sea urchin as a model for
      decades, but our understanding of sea urchin nervous system patterning is
      incomplete. Previous histochemical studies identified multiple neurotransmitters
      in the pluteus larvae of several sea urchin species. However, little is known
      about how, where and when neural subtypes are differentially specified during
      development. Here, we examine the molecular mechanisms of neuronal subtype
      specification in 3 distinct neural subtypes in the Lytechinus variegatus larva.
      We show that these subtypes are specified through Delta/Notch signaling and
      identify a different transcription factor required for the development of each
      neural subtype. Our results show achaete-scute and neurogenin are proneural for
      the serotonergic neurons of the apical organ and cholinergic neurons of the
      ciliary band, respectively. We also show that orthopedia is not proneural but is
      necessary for the differentiation of the cholinergic/catecholaminergic postoral
      neurons. Interestingly, these transcription factors are used similarly during
      vertebrate neurogenesis. We believe this study is a starting point for building a
      neural gene regulatory network in the sea urchin and for finding conserved
      deuterostome neurogenic mechanisms.

PMID- 29331499
TI  - Hspb7 is a cardioprotective chaperone facilitating sarcomeric proteostasis.
AB  - Small heat shock proteins are chaperones with variable mechanisms of action. The
      function of cardiac family member Hspb7 is unknown, despite being identified
      through GWAS as a potential cardiomyopathy risk gene. We discovered that
      zebrafish hspb7 mutants display mild focal cardiac fibrosis and sarcomeric
      abnormalities. Significant mortality was observed in adult hspb7 mutants
      subjected to exercise stress, demonstrating a genetic and environmental
      interaction that determines disease outcome. We identified large sarcomeric
      proteins FilaminC and Titin as Hspb7 binding partners in cardiac cells. Damaged
      FilaminC undergoes autophagic processing to maintain sarcomeric homeostasis. Loss
      of Hspb7 in zebrafish or human cardiomyocytes stimulated autophagic pathways and
      expression of the sister gene encoding Hspb5. Inhibiting autophagy caused
      FilaminC aggregation in HSPB7 mutant human cardiomyocytes and developmental
      cardiomyopathy in hspb7 mutant zebrafish embryos. These studies highlight the
      importance of damage-processing networks in cardiomyocytes, and a previously
      unrecognized role in this context for Hspb7.

PMID- 29331500
TI  - Peripheral modulation of the endocannabinoid system in metabolic disease.
AB  - Dysfunction of the endocannabinoid system (ECS) has been identified in metabolic
      disease. Cannabinoid receptor 1 (CB1) is abundantly expressed in the brain but
      also expressed in the periphery. Cannabinoid receptor 2 (CB2) is more abundant in
      the periphery, including the immune cells. In obesity, global antagonism of
      overexpressed CB1 reduces bodyweight but leads to centrally mediated adverse
      psychological outcomes. Emerging research in isolated cultured cells or tissues
      has demonstrated that targeting the endocannabinoid system in the periphery
      alleviates the pathologies associated with metabolic disease. Further, peripheral
      specific cannabinoid ligands can reverse aspects of the metabolic phenotype. This
      Keynote review will focus on current research on the functionality of peripheral
      modulation of the ECS for the treatment of obesity.

PMID- 29331502
TI  - Contrast-induced nephropathy - an entity to bear in mind and to prevent: A
      nephrological perspective.

PMID- 29331501
TI  - Incorporating upper motor neuron health in ALS drug discovery.
AB  - Amyotrophic lateral sclerosis (ALS) is a complex disease, that affects the motor
      neuron circuitry. After consecutive failures in clinical trials for the past 20
      years, edaravone was recently approved as the second drug for ALS. This generated
      excitement in the field revealed the need to improve preclinical assays for
      continued success. Here, we focus on the importance and relevance of upper motor
      neuron (UMN) pathology in ALS, and discuss how incorporation of UMN survival in
      preclinical assays will improve inclusion criteria for clinical trials and
      expedite the drug discovery effort in ALS and related motor neuron diseases.

PMID- 29331503
TI  - Clinical scores in acute coronary syndrome: When and why should we use them?

PMID- 29331504
TI  - A Systematic Review of Health Care Provider-Perceived Barriers and Facilitators
      to Routine HIV Testing in Primary Care Settings in the Southeastern United
      States.
AB  - Despite efforts to improve HIV screening and testing, many primary care settings
      do not follow established guidelines. The purpose of our systematic review was to
      describe health care providers' perceived barriers and facilitators to testing
      for HIV at poorly used/novel testing sites in the southeastern United States.
      PubMed, CINAHL, and Embase databases were searched for peer-reviewed studies of
      providers' perceived barriers and facilitators to routine HIV testing from
      January 2016 to April 2017 according to the Preferred Reporting Items for
      Systematic Reviews and Meta-Analyses (PRISMA) statement. Of 708 papers retrieved,
      12 met inclusion criteria and were analyzed. Barriers to HIV testing in primary
      care existed at the societal, organizational, and individual levels. Providers
      need continuing sexual health education, including HIV and federal guideline
      updates, and students should have clinical experiences to supplement knowledge
      about sexual health. Clinic protocols should be updated to meet current policy
      guidelines.

PMID- 29331505
TI  - Successful Treatment of Anti-angiotensin II Type 1 Receptor Antibody-Associated
      Rejection in Kidney Transplantation: A Case Report.
AB  - Angiotensin II type 1 receptor (AT1R) antibody, a non-HLA antibody, has been
      found to have a detrimental effect on kidney allografts. Similarly to HLA
      antibodies, recipients who have AT1R antibodies are at risk for allograft
      rejection and poor long-term graft outcome. Besides mediating allograft
      rejections via direct effects on endothelial and vascular smooth muscle without
      complement activation, AT1R antibodies may lead to accelerated hypertension via
      the renin-angiotensin pathway. There has been no definite level of AT1R antibody
      that predicts allograft rejection. Because of a low incidence of AT1R antibody
      associated rejection, there are few reports on specific treatment. The results of
      conventional treatment, which aims to remove these pathologic antibodies
      similarly to the treatment of HLA antibody-associated rejection, have been
      unsatisfactory. Some studies recommend using angiotensin receptor blocker to
      attenuate the adverse effects of AT1R antibody on kidney allograft. Herein we
      present a kidney transplant recipient with AT1R antibody-associated refractory
      allograft rejection who was successfully treated with the use of steroid,
      plasmapheresis, intravenous immunoglobulin, and rituximab.

PMID- 29331506
TI  - Hepatocyte estrogen receptor alpha mediates estrogen action to promote reverse
      cholesterol transport during Western-type diet feeding.
AB  - OBJECTIVE: Hepatocyte deletion of estrogen receptor alpha (LKO-ERalpha) worsens
      fatty liver, dyslipidemia, and insulin resistance in high-fat diet fed female
      mice. However, whether or not hepatocyte ERalpha regulates reverse cholesterol
      transport (RCT) in mice has not yet been reported. METHODS AND RESULTS: Using LKO
      ERalpha mice and wild-type (WT) littermates fed a Western-type diet, we found
      that deletion of hepatocyte ERalpha impaired in vivo RCT measured by the removal
      of 3H-cholesterol from macrophages to the liver, and subsequently to feces, in
      female mice but not in male mice. Deletion of hepatocyte ERalpha decreased the
      capacity of isolated HDL to efflux cholesterol from macrophages and reduced the
      ability of isolated hepatocytes to accept cholesterol from HDL ex vivo in both
      sexes. However, only in female mice, LKO-ERalpha increased serum cholesterol
      levels and increased HDL particle sizes. Deletion of hepatocyte ERalpha increased
      adiposity and worsened insulin resistance to a greater degree in female than male
      mice. All of the changes lead to a 5.6-fold increase in the size of early
      atherosclerotic lesions in female LKO-ERalpha mice compared to WT controls.
      CONCLUSIONS: Estrogen signaling through hepatocyte ERalpha plays an important
      role in RCT and is protective against lipid retention in the artery wall during
      early stages of atherosclerosis in female mice fed a Western-type diet.

PMID- 29331508
TI  - Compartmentalized crosstalk of CFTR and TMEM16A (ANO1) through EPAC1 and ADCY1.
AB  - Airway epithelial cells express both Ca2+ activated TMEM16A/ANO1 and cAMP
      activated CFTR anion channels. Previous work suggested a significant crosstalk of
      intracellular Ca2+ and cAMP signaling pathways, leading to activation of both
      chloride channels. We demonstrate that in airway epithelial cells, stimulation of
      purinergic or muscarinic G-protein coupled receptors (GPCRs) activates TMEM16A
      and CFTR. Additional expression of Gq/11 and phospholipase C coupled GPCRs
      strongly enhanced the crosstalk between Ca2+- and cAMP-dependent signaling.
      Knockdown of endogenous GRCRs attenuated crosstalk and functional coupling
      between TMEM16A and CFTR. The number of receptors did not affect expression or
      membrane localization of TMEM16A or CFTR, but controlled assembly of the local
      signalosome. GPCRs translocate Ca2+-sensitive adenylate cyclase type 1 (ADCY1)
      and exchange protein directly activated by cAMP (EPAC1) to particular plasma
      membrane domains containing GPCRs, CFTR and TMEM16A, thereby producing
      compartmentalized Ca2+ and cAMP signals and significant crosstalk. While
      biosynthesis and membrane trafficking of CFTR requires a functional Golgi
      apparatus, maturation and membrane trafficking of TMEM16A may occur independent
      of the Golgi. Because Ca2+ activated TMEM16A currents are only transient,
      continuous Cl- secretion by airway epithelial cells requires CFTR. The present
      data also explain why receptor-dependent activation of TMEM16A is more efficient
      than direct stimulation by Ca2+.

PMID- 29331509
TI  - Selenolanthionine is the major water-soluble selenium compound in the selenium
      tolerant plant Cardamine violifolia.
AB  - BACKGROUND: Selenium hyperaccumulation in plants often involves the synthesis of
      non-proteinaceous methylated selenoamino acids serving for the elimination of
      excess selenium from plant metabolism to protect plant homeostasis. METHODS: Our
      study aimed at the identification of the main selenium species of the selenium
      hyperaccumulator plant Cardamine violifolia (Brassicaceae) that grows in the wild
      in the seleniferous region of Enshi, China. A sample of this plant (3.7 g Se kg-1
      d.w.) was prepared with several extraction methods and the extracted selenium
      species were identified and quantified with liquid chromatography mass
      spectrometry set-ups. RESULTS: The Cardamine violifolia sample did not contain in
      considerable amount any of the organic selenium species that are often formed in
      hyperaccumulator plants; the inorganic selenium content (mostly as elemental
      selenium) accounted only for <20% of total Se. The most abundant selenium
      compound, accounting for about 40% of total Se was proved to be
      selenolanthionine, a selenium species that has never been unambiguously
      identified before from any selenium containing sample. The identification process
      was completed with chemical synthesis too. The molar ratio of
      lanthionine:selenolanthionine in the water extract was ca. 1:8. CONCLUSIONS:
      Finding selenolanthionine as the main organic selenium species in a plant
      possibly unearths a new way of selenium tolerance. This article is part of a
      Special Issue entitled Selenium research in biochemistry and biophysics - 200
      year anniversary issue, edited by Dr. Elias Arner and Dr. Regina Brigelius-Flohe.

PMID- 29331510
TI  - Effects of sub-minimum inhibitory concentrations of lemon essential oil on the
      acid tolerance and biofilm formation of Streptococcus mutans.
AB  - OBJECTIVES: Lemon essential oil (LEO) is a kind of secondary metabolite from
      lemon peels and has been found to inhibit cariogenic bacteria for decades.
      However, its effects on main cariogenic virulence factors are rarely reported.
      The present study aimed to investigate the effects of sub-minimum inhibitory
      concentrations (sub-MICs) of LEO on the acid tolerance and biofilm formation of
      Streptococcus mutans (S. mutans) and preliminarily reveal the possible underlying
      mechanisms. DESIGNS: Effects of LEO on the acid tolerance and biofilm formation
      of S. mutans were investigated by the broth dilution method and crystal violet
      staining method respectively. The expression of luxS, srtA and spaP gene was also
      determined to explore the underlying mechanism. In addition, Tea polyphenols
      (TP), a major natural inhibitor of cariogenic virulence factors, and limonene
      (LIM), the major component of LEO, were selected as comparisons to evaluate the
      effects of LEO. RESULTS: Sub-MICs of LEO, LIM and TP exhibited a dose-dependent
      inhibition of growth of S. mutans at pH ranging from 4.0 to 7.0. The formation of
      S. mutans biofilm was remarkably inhibited and the inhibitory rates of LEO, LIM
      and TP were 97.87%, 94.88% and 96.01% respectively at 1/2 MIC. Similarly, a down
      regulation was observed in the expression of luxS, srtA and spaP gene at sub-MIC
      levels. CONCLUSIONS: Effects of LEO were similar or slightly stronger than LIM
      and TP, suggesting that LEO might represent a novel, natural anticarious agent
      that inhibited the specific genes associated with bacterial acid tolerance and
      biofilm formation without necessarily affecting the growth of oral bacteria.

PMID- 29331507
TI  - Adropin: An endocrine link between the biological clock and cholesterol
      homeostasis.
AB  - OBJECTIVE: Identify determinants of plasma adropin concentrations, a secreted
      peptide translated from the Energy Homeostasis Associated (ENHO) gene linked to
      metabolic control and vascular function. METHODS: Associations between plasma
      adropin concentrations, demographics (sex, age, BMI) and circulating biomarkers
      of lipid and glucose metabolism were assessed in plasma obtained after an
      overnight fast in humans. The regulation of adropin expression was then assessed
      in silico, in cultured human cells, and in animal models. RESULTS: In humans,
      plasma adropin concentrations are inversely related to atherogenic LDL
      cholesterol (LDL-C) levels in men (n = 349), but not in women (n = 401). Analysis
      of hepatic Enho expression in male mice suggests control by the biological clock.
      Expression is rhythmic, peaking during maximal food consumption in the dark
      correlating with transcriptional activation by RORalpha/gamma. The nadir in the
      light phase coincides with the rest phase and repression by Rev-erb. Plasma
      adropin concentrations in nonhuman primates (rhesus monkeys) also exhibit peaks
      coinciding with feeding times (07:00 h, 15:00 h). The ROR inverse agonists SR1001
      and the 7-oxygenated sterols 7-beta-hydroxysterol and 7-ketocholesterol, or the
      Rev-erb agonist SR9009, suppress ENHO expression in cultured human HepG2 cells.
      Consumption of high-cholesterol diets suppress expression of the adropin
      transcript in mouse liver. However, adropin over expression does not prevent
      hypercholesterolemia resulting from a high cholesterol diet and/or LDL receptor
      mutations. CONCLUSIONS: In humans, associations between plasma adropin
      concentrations and LDL-C suggest a link with hepatic lipid metabolism. Mouse
      studies suggest that the relationship between adropin and cholesterol metabolism
      is unidirectional, and predominantly involves suppression of adropin expression
      by cholesterol and 7-oxygenated sterols. Sensing of fatty acids, cholesterol and
      oxysterols by the RORalpha/gamma ligand-binding domain suggests a plausible
      functional link between adropin expression and cellular lipid metabolism.
      Furthermore, the nuclear receptors RORalpha/gamma and Rev-erb may couple adropin
      synthesis with circadian rhythms in carbohydrate and lipid metabolism.

PMID- 29331512
TI  - A format for reviewing a research paper.

PMID- 29331511
TI  - Maresin 1 regulates autophagy and inflammation in human periodontal ligament
      cells through glycogen synthase kinase-3beta/beta-catenin pathway under
      inflammatory conditions.
AB  - OBJECTIVE: Accumulating lines of evidence suggest that maresin 1 (MaR-1) exerts
      anti-inflammatory effects in many cell types and plays beneficial roles in
      inflammatory disease, such as peritonitis and colitis. Moreover, it has been
      demonstrated that MaR-1 play protective roles against localized aggressive
      periodontitis. However, the function and mechanism of MaR-1 in human periodontal
      ligament cells (PDL) cells from periodontitis are poorly understood. The present
      study aimed to clarify the effects and molecular mechanism of MaR-1 in PDL cell
      survival and inflammation. METHODS: PDL cells were isolated from the middle third
      of the root surface of premolars from four healthy humans; MTT assay and cell
      death detection ELISA assay were used to detect cell survival and apoptosis;
      Inflammatory cytokines level was measured by ELISA assay; RT-PCR and western blot
      was used to measure the mRNA and protein expression in this study. RESULTS: Here
      we found that MaR-1 treatment markedly promotes survival and inhibits apoptosis
      in PDL cell treated by LPS. MaR-1 treatment strikingly suppressed the production
      of LPS-induced pro-inflammatory cytokines IL-6, IL-8, TNF-alpha and IL-1beta. MaR
      1 also promotes autophagy by increasing the ratio of LC3II/LC3I, the level of
      beclin-1 and reduced the expression of p62 in LPS treated PDL cells, which is
      beneficial to cell survival. Moreover, the results showed that MaR-1-mediated
      autophagy is dependent on the glycogen synthase kinase-3beta(GSK-3beta)/beta
      catenin signal pathway. The inhibitor of autophagy 3-MA and the inhibitor of the
      GSK-3beta/beta-catenin signal pathway LiCL both reverse the effects of MaR-1 on
      LPS-treated PDL cell survival and inflammation. CONCLUSION: MaR-1 promotes cell
      survival and alleviates cell inflammation by activating GSK-3beta/beta-catenin
      dependent autophagy. These results provide new insights into the mechanism of
      chronic periodontitis.

PMID- 29331513
TI  - Multiple myeloma and a mischievous pacemaker: A teaching case involving
      irradiation of a cardiovascular implantable electronic device.

PMID- 29331514
TI  - Employment of proteomic and immunological based methods for the identification of
      catalase as novel allergen from banana.
AB  - : Diagnostic reagents based on food allergen extracts often lack sufficient
      sensitivity. The introduction of well characterized food allergens in molecular
      allergy diagnosis has been recognized as valid approach to circumvent
      unstandardized allergen extracts. Banana fruit (Musa acuminata) is a well
      established allergen source which besides six characterized allergens, contains
      unidentified IgE reactive proteins whose clinical relevance remains undefined. By
      employment of a combinatorial peptide ligand library (CPLL) methodology with 2-D
      PAGE, mass spectrometric and 2-D immunoblot analysis, a novel allergen from
      banana fruit was detected in banana as catalase. A recombinant homologue of
      natural catalase was produced, isolated and biochemically characterized. The
      recombinant protein showed IgE reactivity in 7 out of 13 tested patients with
      suspected allergy to banana in immunoblot. Novel banana fruit allergens should be
      added as components to allergen-microarrays for the diagnosis and the monitoring
      of banana allergy. SIGNIFICANCE: By employment of CPLL methodology with 2-D PAGE,
      mass spectrometric and 2-D immunoblot analysis catalase from banana fruit is
      identified as a novel allergen, with proposed designation as Mus a 7. IgE
      reactive recombinant Mus a 7 was produced and should be included in a component
      resolved allergy diagnosis.

PMID- 29331516
TI  - Simultaneous saccharification and aerobic fermentation of high titer cellulosic
      citric acid by filamentous fungus Aspergillus niger.
AB  - Simultaneous saccharification and fermentation (SSF) is the most efficient
      operation in biorefining conversion, but aerobic SSF under high solids loading
      significantly faces the serious oxygen transfer limitation. This study took the
      first insight into an aerobic SSF by high oxygen demanding filamentous fungi in
      highly viscous lignocellulose hydrolysate. The results show that oxygen
      requirement in the aerobic SSF by Aspergillus niger was well satisfied for
      production of cellulosic citric acid. The record high citric acid titer of 136.3
      g/L and the overall conversion yield of 74.9% of cellulose were obtained by the
      aerobic SSF. The advantage of SSF to the separate hydrolysis and fermentation
      (SHF) on citric acid fermentation was compared based on the rigorous Aspen Plus
      modeling. The techno-economic analysis indicates that the minimum citric acid
      selling price (MCSP) of $0.603 per kilogram by SSF was highly competitive with
      the commercial citric acid from starch feedstock.

PMID- 29331517
TI  - Tofu whey wastewater is a promising basal medium for microalgae culture.
AB  - Tofu whey wastewater (TWW) is an abundant, nutrient riched and safety wastewater
      and is regarded as an excellent alternative medium in fermentation. In this
      study, the feasibility of algal cultivation using TWW as the basal medium was
      investigated. Results indicated that through simple pH adjustment, TWW presented
      a better culture performance at autotrophic, heterotrophic, and mixotrophic modes
      compared with that of regular green algae medium, BG-11. The biomass
      productivities of Chlorella pyrenoidosa at each trophic mode were 4.76, 1.97, and
      2.08 times higher than that cultured in BG-11 medium, respectively. Although a
      comparative or even lower lipid and protein content was obtained, much higher
      lipid and protein productivities were obtained in TWW compared to that of BG-11.
      The algal biomass accumulated in TWW can be used to produce high-value products.
      Therefore, TWW is a better alternative medium for efficient algal culture.

PMID- 29331518
TI  - Microwave-assisted ionic liquid-mediated rapid catalytic conversion of non-edible
      lignocellulosic Sunn hemp fibres to biofuels.
AB  - Sunn hemp fibre - a cellulose-rich crystalline non-food energy crop, containing
      75.6% cellulose, 10.05% hemicellulose, 10.32% lignin, with high crystallinity
      (80.17%) and degree of polymerization (650) - is identified as a new non-food
      substrate for lignocellulosic biofuel production. Microwave irradiation is
      employed to rapidly rupture the cellulose's glycosidic bonds and enhance glucose
      yield to 78.7% at 160  degrees C in only 46 min. The reactants - long-chain
      cellulose, ionic liquid, transition metal catalyst, and water - form a polar
      supramolecular complex that rotates under the microwave's alternating polarity
      and rapidly dissipates the electromagnetic energy through molecular collisions,
      thus accelerating glycosidic bond breakage. In 46 min, 1 kg of Sunn hemp fibres
      containing 756 g of cellulose produces 595 g of glucose at 160  degrees C, and
      203 g of hydroxymethyl furfural (furanic biofuel precursor) at 180  degrees C.
      Yeast mediated glucose fermentation produces 75.6% bioethanol yield at 30 
      degrees C, and the ionic liquid is recycled for cost-effectiveness.

PMID- 29331515
TI  - MHC class I loaded ligands from breast cancer cell lines: A potential HLA-I-typed
      antigen collection.
AB  - : To build a catalog of peptides presented by breast cancer cells, we undertook
      systematic MHC class I immunoprecipitation followed by elution of MHC class I
      loaded peptides in breast cancer cells. We determined the sequence of 3196 MHC
      class I ligands representing 1921 proteins from a panel of 20 breast cancer cell
      lines. After removing duplicate peptides, i.e., the same peptide eluted from more
      than one cell line, the total number of unique peptides was 2740. Of the unique
      peptides eluted, more than 1750 had been previously identified, and of these,
      sixteen have been shown to be immunogenic. Importantly, half of these immunogenic
      peptides were shared between different breast cancer cell lines. MHC class I
      binding probability was used to plot the distribution of the eluted peptides in
      accordance with the binding score for each breast cancer cell line. We also
      determined that the tested breast cancer cells presented 89 mutation-containing
      peptides and peptides derived from aberrantly translated genes, 7 of which were
      shared between four or two different cell lines. Overall, the high throughput
      identification of MHC class I-loaded peptides is an effective strategy for
      systematic characterization of cancer peptides, and could be employed for design
      of multi-peptide anticancer vaccines. SIGNIFICANCE: By employing proteomic
      analyses of eluted peptides from breast cancer cells, the current study has built
      an initial HLA-I-typed antigen collection for breast cancer research. It was also
      determined that immunogenic epitopes can be identified using established cell
      lines and that shared immunogenic peptides can be found in different cancer types
      such as breast cancer and leukemia. Importantly, out of 3196 eluted peptides that
      included duplicate peptides in different cells 89 peptides either contained
      mutation in their sequence or were derived from aberrant translation suggesting
      that mutation-containing epitopes are on the order of 2-3% in breast cancer
      cells. Finally, our results suggest that interfering with MHC class I function is
      one of the mechanisms of how tumor cells escape immune system attack.

PMID- 29331519
TI  - Understanding and misunderstanding randomized controlled trials.
AB  - Randomized Controlled Trials (RCTs) are increasingly popular in the social
      sciences, not only in medicine. We argue that the lay public, and sometimes
      researchers, put too much trust in RCTs over other methods of investigation.
      Contrary to frequent claims in the applied literature, randomization does not
      equalize everything other than the treatment in the treatment and control groups,
      it does not automatically deliver a precise estimate of the average treatment
      effect (ATE), and it does not relieve us of the need to think about (observed or
      unobserved) covariates. Finding out whether an estimate was generated by chance
      is more difficult than commonly believed. At best, an RCT yields an unbiased
      estimate, but this property is of limited practical value. Even then, estimates
      apply only to the sample selected for the trial, often no more than a convenience
      sample, and justification is required to extend the results to other groups,
      including any population to which the trial sample belongs, or to any individual,
      including an individual in the trial. Demanding 'external validity' is unhelpful
      because it expects too much of an RCT while undervaluing its potential
      contribution. RCTs do indeed require minimal assumptions and can operate with
      little prior knowledge. This is an advantage when persuading distrustful
      audiences, but it is a disadvantage for cumulative scientific progress, where
      prior knowledge should be built upon, not discarded. RCTs can play a role in
      building scientific knowledge and useful predictions but they can only do so as
      part of a cumulative program, combining with other methods, including conceptual
      and theoretical development, to discover not 'what works', but 'why things work'.

PMID- 29331520
TI  - Vitamin C attenuates biochemical and genotoxic damage in common carp (Cyprinus
      carpio) upon joint exposure to combined toxic doses of fipronil and buprofezin
      insecticides.
AB  - In the present study, potential protective role of Vitamin C (l-ascorbic acid)
      was investigated in aquaria acclimated common carp (Cyprinus carpio) following
      exposure for 96 h to combined toxic doses of fipronil (FP) and buprofezin (BPFN)
      insecticides in combination (FP: 200 MUg/L; 4.57 * 10-7 mol/L and BPFN: 50 mg/L;
      1.64 * 10-4 mol/L). At end of 96 h exposure, fish were supplemented with low (25
      mg/L) and high (50 mg/L) doses of Vitamin C, added once daily to aquaria water
      for continuous three weeks. Appropriate control groups were run in parallel. Fish
      behavior was monitored throughout for signs of toxicity. At completion of
      experiments, liver, kidney, brain and gills were excised for toxicity assessment
      and possible remediation by the Vitamin C through biochemical determination of
      reactive oxygen species (ROS), thiobarbituric acid reactive substances or TBARS,
      reduced glutathione (GSH) and total protein content, levels of catalase (CAT),
      superoxide dismutase (SOD) and peroxidase (POD), and the Comet assay.
      Hepatosomatic index (HSI), condition factor (CF), survival rate (SR), and
      combination index (CI) were also determined. Data were compared statistically at
      p < 0.05. Results showed significant behavioral and biochemical alterations, and
      DNA damage in the fish group exposed to FP and BPFN in combination. In fish
      groups supplemented with Vitamin C following FP and BPFN treatment, significant
      alleviation in tissue damage and toxic effects was represented by substantial
      decreases in ROS and TBARS production (p < 0.001), along with a concomitant
      significant increase in the survival rate, GSH and total protein content, HSI,
      CF, and activities of SOD, CAT and POD enzymes (p < 0.001). Mean tail length of
      comet and percent tail DNA decreased significantly (p < 0.001), which indicated
      amelioration of DNA damage. The study concludes that Vitamin C is an effective
      remedial treatment against FP and BPFN-induced damage in exposed fish.

PMID- 29331521
TI  - Increased transcript levels and kinetic function of pyruvate kinase during severe
      dehydration in aestivating African clawed frogs, Xenopus laevis.
AB  - The African clawed frog, Xenopus laevis, can withstand extremely arid conditions
      through aestivation, resulting in dehydration and urea accumulation. Aestivating
      X. laevis reduce their metabolic rate, and rely on anaerobic glycolysis to meet
      reduced ATP demands. The present study investigated how severe dehydration
      affected the transcript levels, kinetic profile, and phosphorylation state of the
      key glycolytic enzyme pyruvate kinase (PK) in the liver and skeletal muscle of X.
      laevis. Compared to control frogs, severely dehydrated frogs showed an increase
      in the transcript abundance of both liver and muscle isoforms of PK. While the
      kinetics of muscle PK did not differ between dehydrated and control frogs, PK
      from the liver of dehydrated frogs had a lower Km for phosphoenolpyruvate (PEP)
      (38%), a lower Ka for fructose-1,6-bisphosphate (F1,6P2) (32%), and a greater
      activation of PK via F1,6P2 (1.56-fold). PK from dehydrated frogs also had a
      lower phosphorylation-state (25%) in comparison to the enzyme from control frogs
      in the liver. Experimental manipulation of the phosphorylation-state of liver PK
      taken from control frogs by endogenous protein phosphatases resulted in decreased
      phosphorylation, and a similar kinetic profile as seen in dehydrated frogs. The
      physiological consequence of dehydration-induced PK modification appears to
      adjust PK function to remain active during a metabolically depressed state. This
      study provides evidence for the maintenance of PK activity through elevated mRNA
      levels and a dephosphorylation event which activates frog liver PK in the
      dehydrated state in order to facilitate the production of ATP via anaerobic
      glycolysis.

PMID- 29331523
TI  - Negative Evidence of Direct Differentiation from Bone-Marrow Cells to
      Keratinocytes in Normal and Wounded Skin Using Keratin 5-Specific Reporter Mice.

PMID- 29331522
TI  - Nanos3 not nanos1 and nanos2 is a germ cell marker gene in large yellow croaker
      during embryogenesis.
AB  - In this study, three nanos gene subtypes (Lcnanos1, Lcnanos2 and Lcnanos3) from
      Larimichthys crocea, were cloned and characterized. We determined the spatio
      temporal expression patterns of each subtype in tissues as well as the cellular
      localization of mRNA in embryos. Results showed that deduced Nanos proteins have
      two main homology domains: N-terminal CCR4/NOT1 deadenylase interaction domain
      and highly conserved carboxy-terminal region bearing two conserved CCHC zinc
      finger motifs. The expression levels of Lcnanos1 in testis were significantly
      higher than other tissues, followed by heart, brain, eye, and ovary.
      Nevertheless, both Lcnanos2 and Lcnanos3 were restrictedly expressed in testis
      and ovary, respectively. No signals of Lcnanos1 and Lcnanos2 expression were
      detected at any developmental stages during embryogenesis. On the contrary, the
      signals of Lcnanos3 were detected in all stages examined. Lcnanos3 transcripts
      were firstly localized to the distal end of cleavage furrow at the 2-cell stage.
      Subsequently, mounting positive signals started to appear in a small number of
      cells as the embryo developed to blastula stage and early-gastrula stage. As
      development proceeded, positive signals were found in the primitive gonadal
      ridge. These cells of Lcnanos3 positive signals implied the specification of the
      future PGCs at this stage. It also suggested that PGCs of croaker originate from
      four clusters of cells which inherit maternal germ plasm at blastula stage.
      Furthermore, we preliminarily analyzed the migration route of PGCs in embryos of
      L. crocea. In short, this study laid the foundation for studies on specification
      and development of germ cell from L. crocea during embryogenesis.

PMID- 29331524
TI  - Strategies and technical challenges for imaging oligometastatic disease:
      Recommendations from the European Organisation for Research and Treatment of
      Cancer imaging group.
AB  - Patients with oligometastatic disease (OMD) often have controllable symptoms, and
      cures are possible. Technical improvements in surgery and radiotherapy have
      introduced the option of metastasis-directed ablative therapies as an adjunct or
      alternative to standard-of-care systemic therapies. Several clinical trials and
      registries are investigating the benefit of these therapeutic approaches across
      several cancer sites. This requires that patients are correctly included and
      followed with appropriate imaging. This article discusses the evidence and offers
      recommendations for the implementation of standard-of-care (Response Evaluation
      Criteria in Solid Tumours measurements on computed tomography [CT], magnetic
      resonance imaging [MRI] and bone scintigraphy) and advanced imaging modalities
      (functional, metabolic and radionuclide targeted) for identifying and following
      up patients with OMD. Imaging requirements for recognising OMD vary with tumour
      type, metastatic location, and timing of measurement in relation to previous
      treatment. At each point in the disease cycle (diagnosis, response assessment and
      follow-up), imaging must be tailored to the clinical question and the context of
      prior treatment. The differential use of whole-body approaches such as 18F-FDG
      positron emission tomography (PET)/CT, diffusion-weighted MRI, 18F-Choline-PET/CT
      and 68Ga-prostate specific membrane antigen-PET/CT require rationalisation
      depending on clinical risk assessment. Optimal standardised imaging approaches
      will enable OMD trials to document patterns of disease progression and outcomes
      of treatment. Quality assured and quality controlled imaging data included in
      databases such as the European Organisation for Research and Treatment of Cancer
      Imaging platform for the Oligocare trial (a prospective, large-scale
      observational basket study being set up to collect outcome data from patients
      with OMD treated with radiation therapy) will establish a large and high-quality
      imaging warehouse for future research.

PMID- 29331525
TI  - Production and characterization of ectoine using a moderately halophilic strain
      Halomonas salina BCRC17875.
AB  - This study attempted to utilize Halomonas salina BCRC17875 to produce ectoine by
      optimizing the agitation speed and medium composition. In addition, the chemical
      structure of ectoine produced by H. salina BCRC17875 was determined. The results
      indicate that ectoine production reached 3.65 g/L at 38 h of cultivation when the
      agitation rate and NaCl concentration were fixed at 200 rpm and 2.0 M,
      respectively. It reached 9.20 g/L at 44 h of cultivation when the major medium
      components were yeast extract (56 g/L), glutamate (74.40 g/L), and ammonium
      sulfate (14 g/L). After the nitrogen concentration had been evaluated, evaluation
      of the nitrogen concentration revealed that the ectoine production reached 11.80
      g/L at 44 h of cultivation when 56 g/L of yeast extract and 28 g/L of ammonium
      sulfate were used. Ectoine production reached 13.96 g/L at 44 h of cultivation
      when the carbon/nitrogen ratio was fixed at 3/1 using 84 g/L of yeast extract and
      28 g/L of ammonium sulfate. Furthermore, the identification of ectoine were
      identified and characterized by fast atom bombardment mass spectrometry (FAB-MS)
      and 1H NMR. The results demonstrated a fermentation strategy was successful in
      increasing ectoine production, and that the fermentation medium of ectoine had
      commercialization potential.

PMID- 29331527
TI  - Construction of sake yeast with low production of dimethyl trisulfide precursor
      by a self-cloning method.
AB  - Dimethyl trisulfide (DMTS) is the primary component responsible for "hineka", the
      stale aroma of Japanese sake. Deletion of the MRI1 or MDE1 gene of sake yeast,
      encoding 5'-methylthioribose-1-phosphate isomerase and 5'-methylthioribulose-1
      phosphate dehydratase, respectively, has been reported to greatly reduce the
      amount of DMTS precursor (DMTS-P1) in sake and to suppress the formation of DMTS
      during storage. In this study, we constructed sake yeast strains lacking MRI1
      gene function by a self-cloning method. Two methods were applied: in one, a stop
      codon was introduced in the MRI1 ORF by point mutation; in the other, the entire
      MRI1 ORF was deleted from the genome. In both methods, a plasmid vector
      containing drug-resistance and counter-selectable markers was used to introduce
      the mutation. We successfully obtained the strains, which did not contain the
      plasmid sequences, by both methods. Small-scale sake brewing tests using these SC
      strains (strains obtained by the self-cloning method) found that DMTS-P1 was
      hardly detected in sake brewed with SC strains, and DMTS production after sake
      storage was greatly reduced as compared with the parent strain. The components of
      brewed sake were almost the same between the SC and parent strains. These results
      suggest that SC strains can produce sake with higher flavor stability without
      changing the sake brewing properties.

PMID- 29331526
TI  - Valerate production by Megasphaera elsdenii isolated from pig feces.
AB  - Megasphaera elsdenii is able to produce several short-chain fatty acids (SCFAs),
      such as acetate, propionate, butyrate, and valerate. These SCFAs serve as an
      energy source for host animals and play an important role in gut health. In this
      study, M. elsdenii was isolated from pig feces that had been collected from two
      farms located in distinct areas of Japan. These M. elsdenii isolates were
      genotyped, and 7 representative strains were selected. When these 7 strains and
      M. elsdenii JCM 1772T were cultured with lactate for 24 h, all 7 strains produced
      valerate as a predominant SCFA. Therefore, the valerate-producing M. elsdenii
      inhabits a wide area of Japan. In contrast, M. elsdenii JCM 1772T produced
      acetate, propionate, butyrate, and valerate at similar levels. When the Y2
      strain, one of the 7 representative strains, was cultured without lactate, low
      levels of valerate accumulated. In contrast, in a time course of lactate
      fermentation by the Y2 strain, lactate was rapidly consumed, and acetate and
      propionate were produced after 6 h of incubation. Thereafter, acetate and
      propionate were consumed from 6 to 12 h after the start of the incubation, and
      valerate and butyrate were produced. In most of the previously described M.
      elsdenii strains, valerate was not a predominant SCFA. Therefore, the M. elsdenii
      Y2 strain showed an unique metabolism in which valerate was produced as a primary
      end product of lactate fermentation.

PMID- 29331528
TI  - Expression of a thermotolerant laccase from Pycnoporus sanguineus in Trichoderma
      reesei and its application in the degradation of bisphenol A.
AB  - The laccase gene from Pycnoporus sanguineus was cloned and inserted between the
      strong Pcbh1 promoter and the Tcbh1 terminator from Trichoderma reesei to form
      the recombinant plasmid pCH-lac. Using Agrobacterium-mediated technique, the pCH
      lac was integrated into the chromosomes of T. reesei. Twenty positive
      transformants were obtained by employing hygromycin B as a selective agent. PCR
      was used to confirm that the laccase gene was integrated into the chromosomal DNA
      of T. reesei. Laccase production by recombinant transformants was performed in
      shaking flasks, and the activity of laccase reached 8.8 IU/mL after 96-h
      fermentation under a batch process, and 17.7 IU/mL after 144-h fermentation using
      a fed-batch process. SDS-PAGE analysis of the fermentation broth showed that the
      molecular mass of the protein was about 68 kDa, almost the same as that of the
      laccase produced by P. sanguineus, which indicated that laccase was successfully
      expressed in T. reesei and secreted out of the cells. The laccase produced by the
      recombinant T. reesei showed good thermal stability, and could degrade the toxic
      phenolic material bisphenol A efficiently, after 1-h reaction with 0.06 IU/mL
      laccase and 0.5 mmol/L ABTS as the mediator at 60  degrees C and pH 4.5, the
      degradation rate reached 95%, which demonstrated that it had great potential
      value in treating the household garbage and wastewater containing the bisphenol
      A.

PMID- 29331529
TI  - Effect of acids produced from carbohydrate metabolism in cryoprotectants on the
      viability of freeze-dried Lactobacillus and prediction of optimal initial cell
      concentration.
AB  - For the industrial production of probiotics powder, various sugars have been used
      as cryoprotectants to preserve probiotics during freeze-drying. Some of these
      sugars can be metabolized by Lactobacillus with the production of acids during
      the mix. In this study, we investigated the effect of acids on ATPase, beta
      galactosidase, lactate dehydrogenase (LDH), integrity and fluidity of cell
      membrane and the survival rate of Lactobacillus during freeze-drying. In the
      presence of Lactobacillus, acids were produced from cryoprotectants containing
      fermentable sugars before freezing, resulting in a decrease in the pH of the
      bacterial suspension to below 5.0. During freeze-drying, the acids caused a loss
      of viability of Lactobacillus due to aggravated damage to ATPase, beta
      galactosidase and cell membrane fluidity, but not LDH and cell membrane
      integrity. This finding implied that cryoprotectants that do not lead to the
      production of acids are effective in improving the survival rate of freeze-dried
      Lactobacillus. Here, a new formula was proposed for a protectant containing whey
      protein isolate (WPI) and rhamnose, which were not metabolized. In addition,
      linear-regression analyses were performed on the proportion of cryoprotectants
      (M) against cell paste (m), total cell count (N), total surface area (St) and
      total volume (Vt) of bacteria for 100% survival rate. The total surface areas of
      bacteria were found to be highly correlated with the amount of proposed
      cryoprotectant. The following prediction equation was established for the optimal
      initial cell concentration for a 100% survival rate of freeze-dried
      Lactobacillus: N (4pir2+2pil)=(0.66+/-0.03)M.

PMID- 29331530
TI  - A qualitative synthesis of pharmacist, other health professional and lay
      perspectives on the role of community pharmacy in facilitating care for people
      with long-term conditions.
AB  - BACKGROUND: There is increasing interest in an enhanced role for community
      pharmacy (CP) in facilitating care for people with long-term conditions (LTCs).
      It is important to understand the perspectives of stakeholders in order to
      identify key issues that may impact on future development of the role and related
      services. OBJECTIVES: Explore pharmacist, other health professional and lay
      perspectives on the role of CP in facilitating care for people with LTCs.
      METHODS: Synthesis of qualitative research from UK based studies published
      between 2007 and January 2017 using a meta-ethnographic interpretative approach.
      RESULTS: Variation in the conceptualisation of the role of CP in facilitating the
      care of people with LTCs was apparent across and within lay and health
      professional accounts. Despite evidence of positive attitudes and a culture
      amenable to change, there remains a lack of clarity about the existing and
      potential role of the pharmacist in this area. A theoretical framework is
      proposed that highlights the dynamic nature of the process involved in the
      development of lay and health professionals' understanding of the role and
      engagement with services. Influences on this process include experience and
      perceived need, service operationalisation, and ongoing developments within wider
      healthcare policy and commercial environments. Perceived integration with
      existing professional and peer support structures, views about traditional
      medical hierarchies and concerns about potential duplication are important
      influences on the value attributed to the role of CP and the services provided.
      CONCLUSIONS: There is acknowledged potential for an extended role in CP to
      support the care of people with LTCs. To ensure the likelihood of successful
      engagement with patients and positive health outcomes, developments should
      acknowledge influences within and beyond the CP setting. Potential overlap with
      other healthcare services should be explicitly addressed, ensuring this is framed
      and delivered as valued reinforcement with clearly defined boundaries of
      responsibility.

PMID- 29331531
TI  - Profiles of beta-Amyloid Peptides and Key Secretases in Brain Autopsy Samples
      Differ with Sex and APOE epsilon4 Status: Impact for Risk and Progression of
      Alzheimer Disease.
AB  - The APOE epsilon4 allele was originally reported to contribute to risk of
      Alzheimer's disease (AD) in women, yet male and female AD patient-derived data
      are routinely pooled. Histopathological hallmarks of AD include neurofibrillary
      tangles centered on hyperphosphorylated Tau and plaques composed of the beta
      amyloid (Abeta) peptide that is derived by sequential secretase-mediated cleavage
      of the Amyloid Protein Precursor (APP). We chose to examine profiles of Abeta(1
      40), Abeta(1-42), and N-truncated (i.e., p3-related) fragments in the plaque
      associated fraction of autopsied cortical and corresponding hippocampal samples
      from donors with a diagnosis of early-onset (EOAD) and late-onset (LOAD) AD.
      Levels of Abeta(1-40), Abeta(1-42), and the p3 fragment-enriched pool were
      increased in EOAD and LOAD samples, and correlated well within -but not between-
      regions. Counterintuitively, these increases were similar regardless of the AD
      donor's APOE epsilon4 status. Focusing on the donor's sex and APOE epsilon4
      status as nominal variables (i.e., omitting diagnosis from the stratification)
      revealed that increases in Abeta peptides were specific to female carriers of the
      epsilon4 allele and correlated with the proportional expression of BACE1/beta
      secretase and ADAM10/alpha-secretase in the cortex and with nicastrin (gamma
      secretase) expression in the hippocampus. These data preliminarily support the
      possibility that AD follows distinct amyloidogenic processes in males and
      females, and that the APOE epsilon4 allele exerts a major influence on the
      disease process, particularly in women. This knowledge could significantly impact
      the (re)interpretation of unsuccessful outcomes of clinical interventions
      targeting either Abeta peptides directly or the secretases implicated in APP
      processing.

PMID- 29331532
TI  - High-fat Diet Mediates Anxiolytic-like Behaviors in a Time-dependent Manner
      Through the Regulation of SIRT1 in the Brain.
AB  - The consumption of a high-fat diet (HFD) and obesity have been associated not
      only with metabolic diseases but also with neuropsychiatric diseases, such as
      depression and anxiety. However, results on the effects of an HFD on anxiety are
      controversial, since both anxiogenic and anxiolytic effects have been reported.
      In this study, we evaluated the effects of both short- and long-term intake of an
      HFD on anxiety-like behaviors. To explore the impact of time on the association
      between an HFD and anxiety, mice were fed with an HFD for 4 weeks or 12 weeks.
      Compared with control-diet mice, mice given an HFD for 4 weeks displayed
      anxiolytic-like behaviors. At the same time, we observed decreased SIRT1
      expression in the mPFC and the amygdala of HFD-fed mice. Moreover, resveratrol,
      an activator of SIRT1, reversed the anxiolytic-like behaviors in HFD-fed mice.
      However, after 12 weeks of consuming a high-fat diet, mice did not exhibit any
      anti-anxiety behavior or further decreases in SIRT1 expression in the
      aforementioned brain regions compared with CD-fed mice. When EX-527, a SIRT1
      inhibitor, was intraperitoneally injected, we observed anxiolytic effects in the
      CD-fed mice but not in the 12-week HFD-fed mice. Collectively, our data
      demonstrate that exposure to a short-term HFD can induce anxiolytic behaviors,
      which may be associated with decreased SIRT1 in the mPFC and the amygdala.
      However, this effect is abolished when the high-fat diet is extended to 12 weeks.
      Together, these results demonstrate that SIRT1 plays an essential role in
      regulating mood-related behaviors in HFD-fed mice.

PMID- 29331533
TI  - A woman's hand and a lion's heart: Skills and attributes for rural midwifery
      practice in New Zealand and Scotland.
AB  - OBJECTIVE: the complex and challenging nature of rural midwifery is a global
      issue. New Zealand and Scotland both face similar ongoing challenges in
      sustaining a rural midwifery workforce, and understanding the best preparation
      for rural midwifery practice. This study aimed to explore the range of skills,
      qualities and professional expertise needed for remote and rural midwifery
      practice. DESIGN: online mixed methods: An initial questionnaire via a
      confidential SurveyMonkey(r) was circulated to all midwives working with rural
      women and families in New Zealand and Scotland. A follow-up online discussion
      forum offered midwives a secure environment to share their views about the
      specific skills, qualities and challenges and how rural midwifery can be
      sustained. Data presented were analysed using qualitative descriptive thematic
      analysis. SETTING AND PARTICIPANTS: 222 midwives participated in this online
      study with 145 from New Zealand and 77 from Scotland. FINDINGS: underpinning
      rural midwifery practice is the essence of 'fortitude' which includes having the
      determination, resilience, and resourcefulness to deal with the many challenges
      faced in everyday practice and to safeguard midwifery care for women within their
      rural communities. KEY CONCLUSIONS: rural midwives in New Zealand and Scotland
      who work in rural practice specifically enhance skills such as preparedness,
      resourcefulness and developing meaningful relationships with women and other
      colleagues which enables them to safeguard rural birth. IMPLICATIONS FOR
      PRACTICE: findings will inform the preparation of midwives for rural midwifery
      practice.

PMID- 29331534
TI  - Perinatal palliative care: Integration in a United States nurse midwifery
      education program.
AB  - Midwifery students with perinatal palliative care education develop a skillset to
      provide holistic midwifery care to women and families who are experiencing
      stillbirth or life-limiting fetal diagnoses. This paper presents a model of
      perinatal palliative care in a United States midwifery education program. By
      utilizing evidence based practices and national programs, perinatal palliative
      care can be threaded through midwifery curricula to achieve international
      standards of practice and competencies. Most importantly, enhancing perinatal
      palliative care education will better prepare future midwives for when a birth
      outcome is not what was expected at the outset of a pregnancy.

PMID- 29331535
TI  - Estrogen deprivation aggravates cardiometabolic dysfunction in obese-insulin
      resistant rats through the impairment of cardiac mitochondrial dynamics.
AB  - The incidence of cardiovascular disease and metabolic syndrome increases after
      the onset of menopause, suggesting estrogen has a vital role in their prevention.
      Mitochondrial dynamics are known to play an important role in the maintenance of
      cardiac physiological function. However, the effects of estrogen deprivation on
      cardiometabolic status and cardiac mitochondrial dynamics under conditions of
      obese-insulin resistance have never been investigated. We hypothesized that
      estrogen deprivation aggravates cardiac dysfunction through increased cardiac
      mitochondrial fission in obese-insulin resistant rats. Female rats were fed on
      either a high fat (HFD, 57.60% fat) or normal (ND, 19.77% fat) diet for 13 weeks.
      The rats were then divided into 4 groups. Two sham groups (HFS and NDS) and 2
      operated or ovariectomized (HFO and NDO) groups (n = 8/group). Six weeks after
      surgery, metabolic status, heart rate variability (HRV), left ventricular (LV)
      function, cardiac mitochondrial function and dynamics, and metabolic parameters
      were determined. Insulin resistance developed in NDO, HFS and HFO rats as
      indicated by increased plasma insulin and HOMA index. Although rats in both NDO
      and HFS groups had markedly impaired LV function indicated by reduced %LVFS and
      impaired cardiac mitochondrial function, rats in the HFO group had the most
      severe impairments. Moreover, the estrogen deprived rats (NDO and HFO) had
      increased cardiac mitochondrial fission through activation of phosphorylation of
      Drp-1 at serine 616. Our findings indicated that estrogen deprivation caused the
      worsening of LV dysfunction through increased cardiac mitochondrial fission in
      obese-insulin resistant rats.

PMID- 29331536
TI  - Chronic inflammation and sarcopenia: A regenerative cell therapy perspective.
AB  - Sarcopenia is characterized by reduced skeletal muscle mass and strength in older
      individuals. It is one of the leading cause of physical limitation in older
      adults, and associated with wide spectrum of adverse events including disability
      and mortality. The phenomenon of chronic-inflammation or inflamm-aging with aging
      is known to be a major contributor to myriad of geriatric conditions including
      sarcopenia. Recent advances in regenerative medicine, in particular cell therapy
      have opened up new possibilities to ameliorate broad range of inflammatory
      disorders. In this context, we will discuss on possibilities of modulation of the
      chronic-inflammatory activation in older adults using regenerative cell therapy
      strategies. This review is an effort toward reducing the growing burden of
      sarcopenia related disability and dependency in the aging population.

PMID- 29331537
TI  - Preparation of acetylated nanofibrillated cellulose from corn stalk
      microcrystalline cellulose and its reinforcing effect on starch films.
AB  - Acetylated nanofibrillated cellulose (ANFC) with different degrees of
      substitution (DS) was prepared from corn-stalk microcrystalline cellulose (MCC)
      using chemical-mechanical combined processes. The physicochemical properties of
      nanofibrillated cellulose (NFC) and ANFC were investigated together with the
      influence of added nanoparticles on the mechanical properties of starch films.
      The acetylation reaction was monitored by Fourier transform infrared (FT-IR) and
      titration. Particle size and morphological of NFC and ANFC were studied by atomic
      force microscope (AFM). The results suggested that NFC had nano-order-unit web
      like network with mean diameter of ~24 nm. The thermostability of all samples was
      found to decrease as the modification extent rose, and mechanical disposal
      revealed no significant influence on the DS and crystalline structure of
      cellulose. The ANFC with the DS value of 0.35 demonstrated the best enhancement
      effect on starch films, with increased tension strength (TS) by 201%. The tensile
      tests confirmed that the web-like network structure of NFC was more conducive to
      strength, and proper chemical modification could improve the uniform dispersion
      of nano-fillers in starch to result in higher strength performances.

PMID- 29331538
TI  - Differential lipid metabolism outcomes associated with ADRB2 gene polymorphisms
      in response to two dietary interventions in overweight/obese subjects.
AB  - BACKGROUND AND AIMS: A precise nutrigenetic management of hypercholesterolemia
      involves the understanding of the interactions between the individual's genotype
      and dietary intake. The aim of this study was to analyze the response to two
      dietary energy-restricted interventions on cholesterol changes in carriers of two
      ADRB2 polymorphisms. METHODS AND RESULTS: A 4-month nutritional intervention was
      conducted involving two different hypo-energetic diets based on low-fat (LF) and
      moderately high-protein (MHP) dietary patterns. A total of 107 unrelated
      overweight/obese individuals were genotyped for two ADRB2 non-synonymous
      polymorphisms: Arg16Gly (rs1042713) and Gln27Glu (rs1042714). Genotyping was
      performed by next-generation sequencing and haplotypes were phenotypically
      screened. Anthropometric measurements and the biochemical profile were assessed
      by conventional methods. Both diets induced cholesterol decreases at the end of
      both nutritional interventions. Interestingly, phenotypical differences were
      observed according to the Arg16Gly polymorphism. Within the MHP group, Gly16Gly
      homozygotes had lower reductions in total cholesterol (-6.5 mg/dL vs. -24.2
      mg/dL, p = 0.009), LDL-c levels (-1.4 mg/dL vs. -16.5 mg/dL, p = 0.005), and non
      HDL-c (-4.5 mg/dL vs. -21.5 mg/dL, p = 0.008) than Arg16 allele carriers.
      Conversely, within the LF group, Gly16Gly homozygotes underwent similar falls in
      total cholesterol (-18.5 mg/dL vs. -18.7 mg/dL, ns), LDL-c levels (-9.7 mg/dL vs.
      -13.1 mg/dL, ns), and non-HDL-c (-15.3 mg/dL vs. -15.7 mg/dL, ns) than Arg16
      allele carriers. The Gln27Glu polymorphism and the Gly16/Glu27 haplotype showed
      similar, but not greater effects. CONCLUSIONS: An energy-restricted LF diet could
      be more beneficial than a MHP diet to reduce serum cholesterol, LDL-c, and non
      HDL-c among Gly16Gly genotype carriers. CLINICALTRIALS.GOV: Identifier:
      NCT02737267.

PMID- 29331540
TI  - Plant Flowering: Imposing DNA Specificity on Histone-Fold Subunits.
AB  - CONSTANS (CO) is a master regulator of flowering time, although the mechanisms
      underlying its role as a transcriptional regulator are not well understood. The
      DNA-binding domain of CO shares homology with that of NUCLEAR FACTOR YA (NF-YA),
      a subunit of the CCAAT-binding trimer NF-Y. Recent publications indicate that CO
      and its rice homolog HEADING DATE 1 (Hd1) form heterotrimers with the histone
      fold subunits of NF-Y to efficiently bind promoter elements in the florigen
      genes. Differences in the DNA-binding specificities of NF-Y and NF-CO can be
      conceptualized based on our knowledge of the 3D structure of the NF-Y/CCAAT
      complex. Here we discuss the modes of assembly of NF-Y-like heterotrimers and
      possible models for their activity as flexible sequence-specific transcriptional
      regulators.

PMID- 29331541
TI  - Perilesional edema in brain cancer: Independent prognosticator or epiphenomenon
      of biomolecular signature?

PMID- 29331542
TI  - Concurrent chemoradiotherapy alone is feasible for esophageal squamous cell
      carcinoma patients not suitable for surgery.

PMID- 29331539
TI  - Serum vitamin D deficiency and risk of hospitalization for heart failure:
      Prospective results from the Moli-sani study.
AB  - BACKGROUND AND AIMS: Evidence indicates that Vitamin D deficiency may be
      associated with increased risk of cardiovascular disease, although findings on
      risk of heart failure (HF) are controversial. We investigated the relationship
      between serum Vitamin D and the incidence of hospitalization for HF in a large
      prospective cohort of Italian adults. METHODS AND RESULTS: 19,092 (49% men, age
      range 35-99 years) HF-free individuals from the Moli-sani study, with complete
      data on serum Vitamin D (25-hydroxyvitamin) levels and incident hospitalized HF,
      were analysed. The cohort was followed up for a median of 6.2 years. Baseline
      serum Vitamin D levels were categorized in deficient (<10 ng/mL), insufficient
      (10-29 ng/mL), and normal (>=30 ng/mL) Incident cases of hospitalization for HF
      were identified by linkage with the regional hospital discharge registry. Hazard
      ratios (HRs) were calculated using Cox-proportional hazard models. The prevalence
      of normal, insufficient or deficient levels of Vitamin D was 12.2%, 79.6% and
      8.2%, respectively. During follow-up, 562 admissions to hospital for HF were
      identified. The incidence of HF was 1.6%, 2.9% and 5.3%, respectively in subjects
      with normal, insufficient and deficient levels of Vitamin D. After multivariable
      analysis, individuals with deficiency of Vitamin D had a higher risk of
      hospitalization for HF (HR: 1.61, 95%CI: 1.06-2.43) than those with normal
      levels. Further adjustment for subclinical inflammation did not substantially
      change the association between Vitamin D deficiency and HF. CONCLUSION:
      Deficiency of Vitamin D was associated, independently of known HF risk factors,
      with an increased risk of hospitalization for HF in an Italian adult population.

PMID- 29331543
TI  - Consolidation chemotherapy after definite concurrent chemoradiation in patients
      with non-operable esophageal cancer: Is it useful?

PMID- 29331544
TI  - Role of bronchoscopy in foreign body aspiration management in adults: A seven
      year retrospective study.

PMID- 29331545
TI  - Reply by Authors.

PMID- 29331546
TI  - Clinically Localized Prostate Cancer: AUA/ASTRO/SUO Guideline. Part II:
      Recommended Approaches and Details of Specific Care Options.
AB  - PURPOSE: This guideline is structured to provide a clinical framework stratified
      by cancer severity to facilitate care decisions and guide the specifics of
      implementing the selected management options. The summary presented herein
      represents Part II of the two-part series dedicated to Clinically Localized
      Prostate Cancer: AUA/ASTRO/SUO Guideline discussing risk stratification and care
      options by cancer severity. Please refer to Part I for discussion of specific
      care options and outcome expectations and management. MATERIALS AND METHODS: The
      systematic review utilized in the creation of this guideline was completed by the
      Agency for Healthcare Research and Quality and through additional supplementation
      by ECRI Institute. This review included articles published between January 2007
      and March 2014 with an update search conducted through August 2016. When
      sufficient evidence existed, the body of evidence for a particular treatment was
      assigned a strength rating of A (high), B (moderate), or C (low) for support of
      Strong, Moderate, or Conditional Recommendations. Additional information is
      provided as Clinical Principles and Expert Opinions (table 2 in supplementary
      unabridged guideline, http://jurology.com/). RESULTS: The AUA (American
      Urological Association), ASTRO, and SUO (Society of Urologic Oncology) formulated
      an evidence-based guideline based on a risk stratified clinical framework for the
      management of localized prostate cancer. CONCLUSIONS: This guideline attempts to
      improve a clinician's ability to treat patients diagnosed with localized prostate
      cancer, but higher quality evidence in future trials will be essential to improve
      the level of care for these patients. In all cases, patient preferences should be
      considered when choosing a management strategy.

PMID- 29331547
TI  - Editorial Comment.

PMID- 29331549
TI  - Is sequence awareness mandatory for perceptual sequence learning: An assessment
      using a pure perceptual sequence learning design.
AB  - We examined the role of sequence awareness in a pure perceptual sequence learning
      design. Participants had to react to the target's colour that changed according
      to a perceptual sequence. By varying the mapping of the target's colour onto the
      response keys, motor responses changed randomly. The effect of sequence awareness
      on perceptual sequence learning was determined by manipulating the learning
      instructions (explicit versus implicit) and assessing the amount of sequence
      awareness after the experiment. In the explicit instruction condition (n = 15),
      participants were instructed to intentionally search for the colour sequence,
      whereas in the implicit instruction condition (n = 15), they were left uninformed
      about the sequenced nature of the task. Sequence awareness after the sequence
      learning task was tested by means of a questionnaire and the process-dissociation
      procedure. The results showed that the instruction manipulation had no effect on
      the amount of perceptual sequence learning. Based on their report to have
      actively applied their sequence knowledge during the experiment, participants
      were subsequently regrouped in a sequence strategy group (n = 14, of which 4
      participants from the implicit instruction condition and 10 participants from the
      explicit instruction condition) and a no-sequence strategy group (n = 16, of
      which 11 participants from the implicit instruction condition and 5 participants
      from the explicit instruction condition). Only participants of the sequence
      strategy group showed reliable perceptual sequence learning and sequence
      awareness. These results indicate that perceptual sequence learning depends upon
      the continuous employment of strategic cognitive control processes on sequence
      knowledge. Sequence awareness is suggested to be a necessary but not sufficient
      condition for perceptual learning to take place.

PMID- 29331548
TI  - Effect of outpatient antibiotics for urinary tract infections on antimicrobial
      resistance among commensal Enterobacteriaceae: a multinational prospective cohort
      study.
AB  - OBJECTIVES: We quantified the impact of antibiotics prescribed in primary care
      for urinary tract infections (UTIs) on intestinal colonization by ciprofloxacin
      resistant (CIP-RE) and extended-spectrum beta-lactamase-producing
      Enterobacteriaceae (ESBL-PE), while accounting for household clustering. METHODS:
      Prospective cohort study from January 2011 to August 2013 at primary care sites
      in Belgium, Poland and Switzerland. We recruited outpatients requiring
      antibiotics for suspected UTIs or asymptomatic bacteriuria (exposed patients),
      outpatients not requiring antibiotics (non-exposed patients), and one to three
      household contacts for each patient. Faecal samples were tested for CIP-RE, ESBL
      PE, nitrofurantoin-resistant Enterobacteriaceae (NIT-RE) and any
      Enterobacteriaceae at baseline (S1), end of antibiotics (S2) and 28 days after S2
      (S3). RESULTS: We included 300 households (205 exposed, 95 non-exposed) with 716
      participants. Most exposed patients received nitrofurans (86; 42%) or
      fluoroquinolones (76; 37%). CIP-RE were identified in 16% (328/2033) of samples
      from 202 (28%) participants. Fluoroquinolone treatment caused transient
      suppression of Enterobacteriaceae (S2) and subsequent two-fold increase in CIP-RE
      prevalence at S3 (adjusted prevalence ratio (aPR) 2.0, 95% CI 1.2-3.4), with
      corresponding number-needed-to-harm of 12. Nitrofurans had no impact on CIP-RE
      (aPR 1.0, 95% CI 0.5-1.8) or NIT-RE. ESBL-PE were identified in 5% (107/2058) of
      samples from 71 (10%) participants, with colonization not associated with
      antibiotic exposure. Household exposure to CIP-RE or ESBL-PE was associated with
      increased individual risk of colonization: aPR 1.8 (95% CI 1.3-2.5) and 3.4 (95%
      CI 1.3-9.0), respectively. CONCLUSIONS: These findings support avoidance of
      fluoroquinolones for first-line UTI therapy in primary care, and suggest
      potential for interventions that interrupt household circulation of resistant
      Enterobacteriaceae.

PMID- 29331551
TI  - Difficult Removal of a Kinked Swan-Ganz Catheter.

PMID- 29331550
TI  - Double-Lumen Endotracheal Tube Placement: Knowing Depth of Insertion Firsthand
      May Make a Difference.

PMID- 29331552
TI  - Malperfusion During Hypothermic Antegrade Cerebral Perfusion: Cerebral Perfusion
      Index-An Early Indicator Compared to Cerebral Oximetry.

PMID- 29331553
TI  - Unexpected Findings in a Man with a Repaired Type A Aortic Dissection and a New
      Stroke.

PMID- 29331554
TI  - Potential Role of Transfontanelle Ultrasound for Infants Undergoing Modified
      Blalock-Taussig Shunt.
AB  - OBJECTIVE: Transfontanelle ultrasound is a noninvasive method for assessing
      cerebral blood flow in neonates and infants. The authors applied this technique
      as a point-of-care tool, before and after modified Blalock-Taussig shunt
      procedure, to evaluate cerebral perfusion. DESIGN: Retrospective, observational
      study. SETTING: Tertiary care children's hospital. PARTICIPANTS: Ten infants
      undergoing modified Blalock-Taussig shunt procedure. OBSERVATION: Transfontanelle
      ultrasound examinations with modified resistive index were analyzed before and
      after the modified Blalock-Taussig shunt procedure. MEASUREMENTS AND MAIN
      RESULTS: Two infants died and 2 patients required a revision procedure due to
      shunt thrombosis. Baseline-modified resistive index and regional cerebral
      oxygenation were comparable between the right and left hemisphere. However, after
      the procedure, the modified resistive index decreased at both sides of the
      internal carotid arteries compared with baseline values (p value right side =
      0.012, left side = 0.036) and was greater at the ipsilateral internal carotid
      arteries with the shunt (p = 0.012, mean difference = 0.07, 95% confidence
      interval [CI] 0.02-0.12). Four infants with the large patent ductus arteriosus
      presented diastolic reverse flows at both internal carotid arteries at baseline.
      However, the diastolic reverse flow disappeared after the procedure. An infant
      who developed diastolic reverse flow after the procedure, died. CONCLUSIONS:
      Transfontanelle ultrasound is a feasible tool for assessing the pattern of shunt
      flow and cerebral perfusion before and after the modified Blalock-Taussig shunt
      procedure. The transfontanelle ultrasound examinations may have potential role in
      assessing "over-shunting," but it needs more studies.

PMID- 29331555
TI  - Preoperative Thromboelastographic Profile of Patients with Congenital Heart
      Disease: Association of Hypercoagulability and Decreased Heparin Response.
AB  - OBJECTIVE: To describe the demographic and thromboelastographic characteristics
      of patients with congenital heart disease presenting with decreased heparin
      response before cardiac surgery. DESIGN: Retrospective, observational study.
      SETTING: Single institution, tertiary, academic, university hospital.
      PARTICIPANTS: The study comprised 496 pediatric and adult patients undergoing
      cardiac surgery for congenital heart disease. INTERVENTIONS: Retrospective review
      of medical records. MEASUREMENTS AND MAIN RESULTS: Data on preoperative
      thromboelastography (TEG), demographics, and response to heparin were collected
      retrospectively. Logistic regression analysis was used to study the association
      between TEG and response to heparin. Decreased heparin response (defined as
      activated clotting time <480 s initial bolus of 300 U/kg heparin) was observed in
      23.6% of patients presenting for surgery. Age distribution and preoperative
      coagulation profiles were similar for both nonresponders and responders to
      heparin. Preoperatively, nonresponders demonstrated all thromboelastrographic
      characteristics consistent with a hypercoagulable profile (shorter reaction time,
      K value, wider angle, and maximum amplitude). Univariate logistic regression
      identified all TEG variables significantly associated with decreased heparin
      response. After adjustment for age, procedure type, and the presence of cyanosis,
      a multivariate logistic regression model identified the TEG variable K (<=1.3
      min) as being significantly associated with decreased heparin response (odds
      ratio 3.7; confidence interval 2.3-5.8; p < 0.0001). CONCLUSIONS: Decreased
      response to heparin before cardiac surgery in patients with congenital heart
      disease is associated with preoperative hypercoagulability identified using a
      viscoelastic test. Additional studies are needed to better understand the
      etiology of decreased heparin response and potential clinical strategies to
      improve anticoagulation management.

PMID- 29331556
TI  - Polypoidal Choroidal Vasculopathy: Definition, Pathogenesis, Diagnosis, and
      Management.
AB  - Polypoidal choroidal vasculopathy (PCV) is an age-related macular degeneration
      (AMD) subtype and is seen particularly in Asians. Previous studies have suggested
      disparity in response to intravitreal injections of anti-vascular endothelial
      growth factor (VEGF) agents between PCV and typical AMD, and thus, the preferred
      treatment for PCV has remained unclear. Recent research has provided novel
      insights into the pathogenesis of PCV, and imaging studies based on OCT suggest
      that PCV belongs to a spectrum of conditions characterized by pachychoroid, in
      which disturbance in the choroidal circulation seems to be central to its
      pathogenesis. Advances in imaging, including enhanced depth imaging, swept-source
      OCT, en face OCT, and OCT angiography, have facilitated the diagnosis of PCV.
      Importantly, 2 large, multicenter randomized clinical trials evaluating the
      safety and efficacy of anti-VEGF monotherapy and combination with photodynamic
      therapy (PDT) recently reported initial first-year outcomes, providing level I
      evidence to guide clinicians in choosing the most appropriate therapy for PCV. In
      this review, we summarize the latest updates in the epidemiologic features,
      pathogenesis, and advances in imaging and treatment trials, with a focus on the
      most recent key clinical trials. Finally, we propose current management
      guidelines and recommendations to help clinicians manage patients with PCV.
      Remaining gaps in current understanding of PCV, such as significance of polyp
      closure, high recurrence rate, and heterogeneity within PCV, are highlighted
      where further research is needed.

PMID- 29331557
TI  - Soil-to-plant transfer factors of natural radionuclides (226Ra and 40K) in
      selected Thai medicinal plants.
AB  - A soil-to-plant transfer factor (TF) is an important parameter that could be used
      to estimate radionuclides levels in medicinal plants. This work reports
      concentrations of natural radionuclides (226Ra and 40K) and TFs in six Thai
      medicinal plants grown in central Thailand using an HPGe gamma ray spectrometer.
      Either root, leaf, or flower parts of each medicinal plant were selected for use
      in the investigation according to their practical uses in traditional medicine.
      The results showed that due to K being essential in plants, 40K had higher
      arithmetic means of activity concentrations and geometric means of TFs (geometric
      standard deviations in parentheses) of 610 +/- 260 Bq kg-1 dry weight (DW) and
      2.0 (1.4), respectively, than 226Ra, which had the activity concentrations and
      TFs of 4.8 +/- 2.6 Bq kg-1 DW and 0.17 (1.8), respectively. The results also
      showed that the leaves of medicinal plants had higher activity concentrations and
      TFs than root and flower parts, probably due to higher metabolic activities in
      leaves. Furthermore, there was good agreement between the results from the
      current work and other similar reports on medicinal plants. The information
      obtained from this work could strengthen knowledge of natural radionuclides in
      plants and particularly increase available TF data on Thai medicinal plants.

PMID- 29331558
TI  - High-resolution 129I bomb peak profile in an ice core from SE-Dome site,
      Greenland.
AB  - 129I in natural archives, such as ice cores, can be used as a proxy for human
      nuclear activities, age marker, and environmental tracer. Currently, there is
      only one published record of 129I in ice core (i.e., from Fiescherhorn Glacier,
      Swiss Alps) and its limited time resolution (1-2 years) prevents the full use of
      129I for the mentioned applications. Here we show 129I concentrations in an ice
      core from SE-Dome, Greenland, covering years 1956-1976 at a time resolution of ~6
      months, the most detailed record to date. Results revealed 129I bomb peaks in
      years 1959, 1962, and 1963, associated to tests performed by the former Soviet
      Union, one year prior, in its Novaya Zemlya test site. All 129I bomb peaks were
      observed in winter (1958.9, 1962.1, and 1963.0), while tritium bomb peaks,
      another prominent radionuclide associated with nuclear bomb testing, were
      observed in spring or summer (1959.3, and 1963.6; Iizuka et al., 2017). These
      results indicate that 129I bomb peaks can be used as annual and seasonal age
      markers for these years. Furthermore, we found that 129I recorded nuclear fuel
      reprocessing signals and that these can be potentially used to correct timing of
      estimated 129I releases during years 1964-1976. Comparisons with other published
      records of 129I in natural archives showed that 129I can be used as common age
      marker and tracer for different types of records. Most notably, the 1963 129I
      bomb peak can be used as common age marker for ice and coral cores, providing the
      means to reconcile age models and associated trends from the polar and tropical
      regions, respectively.

PMID- 29331559
TI  - Experience of on-site disposal of production uranium-graphite nuclear reactor.
AB  - The paper reported the experience gained in the course of decommissioning EI-2
      Production Uranium-Graphite Nuclear Reactor. EI-2 was a production Uranium
      Graphite Nuclear Reactor located on the Production and Demonstration Center for
      Uranium-Graphite Reactors JSC (PDC UGR JSC) site of Seversk City, Tomsk Region,
      Russia. EI-2 commenced its operation in 1958, and was shut down on December 28,
      1990, having operated for the period of 33 years all together. The extra pure
      grade graphite for the moderator, water for the coolant, and uranium metal for
      the fuel were used in the reactor. During the operation nitrogen gas was passed
      through the graphite stack of the reactor. In the process of decommissioning the
      PDC UGR JSC site the cavities in the reactor space were filled with clay-based
      materials. A specific composite barrier material based on clays and minerals of
      Siberian Region was developed for the purpose. Numerical modeling demonstrated
      the developed clay composite would make efficient geological barriers preventing
      release of radionuclides into the environment.

PMID- 29331560
TI  - The effects of sediment transport on temporal variation in radiocesium
      concentrations in very shallow water off the southern coast of Fukushima, Japan.
AB  - We studied the very shallow coastal water off Iwaki City, Fukushima Prefecture,
      and investigated: (1) temporal variation in 137Cs concentrations; (2) particle
      size distribution of sediments; and (3) the effect on variation by waves,
      component-fractionated concentration of radiocesium and mineral composition at
      three sampling stations (Yotsukura, Ena rocky reef and Ena sandy station). There
      was a decline in 137Cs concentrations in sediment samples at all sampling
      stations between 425 and 1173 days after the accident. All stations had
      fluctuations in 137Cs concentrations between 425 and 800 days. At Ena sandy
      station and Ena rocky reef stations the declines in 137Cs concentrations slowed
      from about 800 days after the accident. Fluctuations in particle median diameters
      were seen, as well as in 137Cs concentrations. At Yotsukura, where the
      fluctuation in median diameter was small, a constant decrease in 137Cs
      concentrations was observed. We considered that bioturbation may contribute the
      constant decrease. At Ena sandy station, where the fluctuation of the median
      diameter was large, the fluctuation in 137Cs concentrations was also large. The
      movement of sediments was evaluated by the Shields parameter, and results
      indicated that at any station where the sediment was moved more frequently, the
      fluctuation in 137Cs concentrations was also large. The highly contaminated small
      particles moved from our stations due to wave action between 425 and 800 days
      after the accident. The remaining relatively large particles might contribute to
      the slowing down in reduction of 137Cs concentrations from 800 days after the
      accident. However, the 137Cs concentrations in sediments in very shallow water
      off the southern coast of Fukushima may continue to decline over time.

PMID- 29331561
TI  - Long-term outcome of neurological Wilson's disease.
AB  - INTRODUCTION: Aim of the study was to characterize the clinical spectrum of long
      term treated patients with Wilson's disease (WD) and to identify risk factors
      influencing long-term outcome. METHODS: In a cross-sectional study 30 WD-patients
      being treated for at least 2.5 and up to 31 years underwent a detailed clinical
      investigation, scoring of clinical findings yielding 7 motor and 3 non-motor
      subscores as well as laboratory testing. A factor analysis of these subscores and
      laboratory parameters was performed to detect those items with the highest
      influence on outcome, an ANOVA and subgroup analysis tested the influence of age,
      age at onset of diagnosis and duration of treatment on outcome. A correlation
      analysis was performed between clinical subscores and laboratory findings.
      RESULTS: Three factors (F1-F3) characterized the clinical outcome (F1: tremor and
      pathological reflexes; F2: dystonia and dysarthria; F3: cerebellar abnormalities
      and gait), and three factors the laboratory findings (LF1: serum level of
      ceruloplasmin; LF2: liver enzymes; LF3: INR). Mildly affected patients had an
      elevated 24 h urinary copper excretion, more affected patients presented with
      elevated liver enzymes. Six of the 7 motor subscores did not change with duration
      of treatment, whereas tremor (p < .04), the total score (p < .02) and especially
      the non-motor items (p < .001) significantly increased with duration of
      treatment. The outcome of patients with neuropsychiatric abnormalities was
      significantly worse (p < .01) compared to the rest of the patients. CONCLUSIONS:
      Long-term outcome in WD is influenced by patient's compliance and neurological
      comorbidity.

PMID- 29331562
TI  - NADPH oxidases 2 activation in patients with Parkinson's disease.

PMID- 29331563
TI  - Trends in Premature Mortality Due to Heart Failure by Autonomous Community in
      Spain: 1999 to 2013.
AB  - INTRODUCTION AND OBJECTIVES: Heart failure (HF) is a major public health problem,
      and the prevalence increases with age. In Spain, there are considerable
      differences between autonomous communities. The aim of this study was to analyze
      trends in premature mortality due to HF between 1999 and 2013 in Spain by
      autonomous community. METHODS: We analyzed data on mortality due to HF in Spanish
      residents aged 0 to 75 years by autonomous community between 1999 and 2013. Data
      were collected from files provided by the Spanish Statistics Office. Age-adjusted
      mortality rates were analyzed and the average annual percentage rate was
      estimated by Poisson models. RESULTS: Mortality due to HF represented 10.9% of
      total mortality. In 2013, the national age-adjusted rate was 2.98 deaths in men
      and 1.29 deaths in women per 100 000 inhabitants, with an annual mean reduction
      of 2.27% and 4.53%, respectively. In men, average mortality showed the greatest
      reduction in Castile-La-Mancha (6.30%). In Cantabria, average mortality
      significantly increased (3.97%). In women, average mortality showed the greatest
      decrease in the Chartered Community of Navarre (15.17%). CONCLUSIONS: During the
      study period, mortality due to HF showed an overall average decrease, both
      nationally and by autonomous community. This decrease was more pronounced in
      women than in men. Premature mortality significantly decreased in most-but not
      all-autonomous communities.

PMID- 29331564
TI  - Direct renin inhibition is not enough to prevent reactive oxygen species
      generation and vascular dysfunction in renovascular hypertension.
AB  - Renin-angiotensin system activation promotes oxidative stress and endothelial
      dysfunction. However, no previous study has examined the effects of the renin
      inhibitor aliskiren, either alone or combined with angiotensin II type 1
      antagonists on alterations induced by two-kidney, one-clip (2K1C) hypertension.
      We compared the vascular effects of aliskiren (50mg/kg/day), losartan
      (10mg/kg/day), or both by gavage for 4 weeks in 2K1C and control rats. Treatment
      with losartan, aliskiren, or both exerted similar antihypertensive effects.
      Aliskiren lowered plasma Ang I concentrations in sham rats and in hypertensive
      rats treated with aliskiren or with both drugs. Aliskiren alone or combined with
      losartan decreased plasma angiotensin II concentrations measured by high
      performance liquid chromatography, whereas losartan alone had no effects. In
      contrast, losartan alone or combined with aliskiren abolished hypertension
      induced increases in aortic angiotensin II concentrations, whereas aliskiren
      alone exerted no such effects. While hypertension enhanced aortic oxidative
      stress assessed by dihydroethidium fluorescence and by lucigenin
      chemiluminescence, losartan alone or combined with aliskiren, but not aliskiren
      alone, abolished this alteration. Hypertension impaired aortic relaxation induced
      by acetylcholine, and losartan alone or combined with aliskiren, but not
      aliskiren alone, reversed this alteration. Losartan alone or combined with
      aliskiren, but not aliskiren alone, increased plasma nitrite concentrations in
      2K1C rats. These findings show that antihypertensive effects of aliskiren do not
      prevent hypertension-induced vascular oxidative stress and endothelial
      dysfunction. These findings contrast those found with losartan and suggest that
      renin inhibition is not enough to prevent hypertension-induced impaired redox
      biology and vascular dysfunction.

PMID- 29331565
TI  - Saroglitazar reduces obesity and associated inflammatory consequences in murine
      adipose tissue.
AB  - Prevailing knowledge links chronic low-grade inflammation in the adipose tissue
      to obesity and its associated metabolic complications. In this study, we
      evaluated immunometabolic effects of a recently launched dual peroxisome
      proliferator-activated receptor (PPAR) alpha & gamma agonist 'Saroglitazar' in a
      mouse model of diet-induced obesity (DIO). Body composition analysis revealed
      that saroglitazar treatment promoted hepatic weight gain, while attenuated
      epididymal white adipose tissue (eWAT) mass in DIO. In the eWAT of saroglitazar
      treated mice, histological analysis showed reduced adipocyte hypertrophy and
      matrix deposition (picrosirius red staining). Immunological profiling of stromal
      vascular fraction isolated from eWAT showed decreased pro-inflammatory cells (M1
      macrophages, CD4 and CD8 T-cells) and increased anti-inflammatory M2 macrophages.
      Gene expression and western blot analysis suggested that saroglitazar promoted
      energy expenditure machinery and attenuated inflammatory as well as fibrotic
      markers in eWAT during DIO. In conclusion, for the first time we are reporting
      immunometabolic effects of dual PPARalpha & gamma agonist saroglitazar in DIO and
      insulin resistance (IR). Saroglitazar exerted its beneficial effects on adipose
      tissue by limiting, diet-induced adipose tissue dysfunction, adipocyte
      hypertrophy, adipocyte cell damage and extracellular matrix deposition in
      obesity.

PMID- 29331566
TI  - Editorial Comment.

PMID- 29331567
TI  - Author Reply.

PMID- 29331569
TI  - Salinivibrio kushneri sp. nov., a moderately halophilic bacterium isolated from
      salterns.
AB  - Ten Gram-strain-negative, facultatively anaerobic, moderately halophilic
      bacterial strains, designated AL184T, IB560, IB563, IC202, IC317, MA421, ML277,
      ML318, ML328A and ML331, were isolated from water ponds of five salterns located
      in Spain. The cells were motile, curved rods and oxidase and catalase positive.
      All of them grew optimally at 37 degrees C, at pH 7.2-7.4 and in the presence of
      7.5% (w/v) NaCl. Based on phylogenetic analyses of the 16S rRNA, the isolates
      were most closely related to Salinivibrio sharmensis BAGT (99.6-98.2% 16S rRNA
      gene sequence similarity) and Salinivibrio costicola subsp. costicola ATCC 35508T
      (99.0-98.1%). According to the MLSA analyses based on four (gyrB, recA, rpoA and
      rpoD) and eight (ftsZ, gapA, gyrB, mreB, pyrH, recA, rpoA and topA) concatenated
      gene sequences, the most closely relatives were S. siamensis JCM 14472T (96.8
      95.4% and 94.9-94.7%, respectively) and S. sharmensis DSM 18182T (94.0-92.6% and
      92.9-92.7%, respectively). In silico DNA-DNA hybridization (GGDC) and average
      nucleotide identity (ANI) showed values of 23.3-44.8% and 80.2-91.8%,
      respectively with the related species demonstrating that the ten isolates
      constituted a single novel species of the genus Salinivibrio. Its pangenome and
      core genome consist of 6041 and 1230 genes, respectively. The phylogeny based on
      the concatenated orthologous core genes revealed that the ten strains form a
      coherent phylogroup well separated from the rest of the species of the genus
      Salinivibrio. The major cellular fatty acids of strain AL184T were C16:0 and
      C18:1. The DNA G+C content range was 51.9-52.5mol% (Tm) and 50.2-50.9mol%
      (genome). Based on the phylogenetic-phylogenomic, phenotypic and chemotaxonomic
      data, the ten isolates represent a novel species of the genus Salinivibrio, for
      which the name Salinivibrio kushneri sp. nov. is proposed. The type strain is
      AL184T (=CECT 9177T=LMG 29817T).

PMID- 29331568
TI  - Overall survival and oncological outcomes after partial nephrectomy and radical
      nephrectomy for cT2a renal tumors: A collaborative international study from the
      French kidney cancer research network UroCCR.
AB  - BACKGROUND: Partial nephrectomy (PN) is recommended as first-line treatment for
      cT1 stage kidney tumors because of a better renal function and probably a better
      overall survival than radical nephrectomy (RN). For larger tumors, PN has a
      controversial position due to lack of evidence showing good cancer control. The
      aim of this study was to compare the results of PN and RN in cT2a stage on
      overall survival and oncological results. METHOD: A retrospective international
      multicenter study was conducted in the frame of the French kidney cancer research
      network (UroCCR). We considered all patients aged>=18 years who underwent
      surgical treatment for localized renal cell carcinoma (RCC) stage cT2a (7.1-10cm)
      between 2000 and 2014. Cox and Fine-Gray models were performed to analyze overall
      survival (OS), cancer specific survival (CSS) and cancer-free survival (CFS).
      Comparison between PN and RN was realized after an adjustment by propensity score
      considering predefined confounding factors: age, sex, tumor size, pT stage of the
      TNM classification, histological type, ISUP grade, ASA score. RESULTS: A total of
      267 patients were included. OS at 3 and 5 years was 93.6% and 78.7% after PN and
      88.0% and 76.2% after RN, respectively. CSS at 3 and 5 years was 95.4% and 80.2%
      after PN and 91.0% and 85.0% after RN. No significant difference between groups
      was found after propensity score adjustment for OS (HR 0.87, 95% CI: 0.37-2.05,
      P=0.75), CSS (HR 0.52, 95% CI: 0.18-1.54, P=0.24) and CFS (HR 1.02, 95% CI: 0.50
      2.09, P=0.96). CONCLUSION: PN seems equivalent to RN for OS, CSS and CFS in cT2a
      stage kidney tumors. The risk of recurrence is probably more related to
      prognostic factors than the surgical technique. The decision to perform a PN
      should depend on technical feasibility rather than tumor size, both to imperative
      and elective situation. LEVEL OF EVIDENCE: 4.

PMID- 29331570
TI  - Meningeal marginal zone B-cell lymphoma: The meningioma trap.
AB  - OBJECTIVE: To report a case of marginal zone MALT lymphoma of the temporal dura
      mater, initially mistaken for temporal meningioma. CASE REPORT: A 60-year-old
      immunocompetent woman, followed for more than 10 years for temporal meningioma
      causing vertigo and mixed hearing loss, presented with cervical lymphadenopathy,
      revealing marked progression of an intracranial lesion, leading to a diagnosis of
      marginal zone MALT lymphoma based on histological examination of a cervical lymph
      node. Treatment with 6 cycles of rituximab and bendamustine allowed complete
      remission of cervical lymph node and intracranial lesions, confirming the
      diagnosis of temporal dural mater lymphoma. CONCLUSION: Primary dural lymphoma
      must be part of the differential diagnosis of meningioma. Long-term follow-up
      allows correction of the diagnosis.

PMID- 29331571
TI  - Interdepartmental imaging protocol for clinically based three-dimensional
      computed tomography can provide accurate measurement of glenoid version.
AB  - BACKGROUND: Conventional computed tomography (CT) is not accurate for glenoid
      version measurement. This study sought to examine the feasibility of an
      interdepartmental protocol implemented between orthopedic surgery and radiology
      departments for acquisition of anatomic axial CT images and to validate the
      glenoid version measured through such a protocol. MATERIALS AND METHODS: Data of
      30 conventional CT scans of 10 normal and 20 osteoarthritic glenoids were
      transferred to clinical 3-dimensional imaging software by a radiology technician
      trained for the study. The technician independently reoriented the scapulae to
      generate anatomic CT images. A separate team of orthopedic researchers used
      laboratory-based 3-dimensional reconstruction software (Mimics; Materialise,
      Leuven, Belgium) to generate anatomic axial images. Three independent examiners
      measured glenoid version on the conventional CT, reoriented anatomic CT, and
      Mimics images at the superior, middle, and inferior levels. Data were analyzed
      using the Mimics data as the "gold standard." RESULTS: Reoriented anatomic CT
      images generated by the technician resulted in almost identical version
      measurements to the Mimics images in both normal and arthritic glenoids. The
      conventional CT images had poor agreement with the Mimics images in normal
      glenoids but had good agreement in arthritic glenoids. Both normal and arthritic
      glenoids had increased retroversion superiorly (P < .05), and this phenomenon was
      significantly exaggerated on the conventional CT images (P < .05). CONCLUSIONS:
      This study demonstrated that an interdepartmental protocol can produce reoriented
      anatomic axial CT images on which true glenoid version can be accurately
      measured. Such an institutional protocol would help surgeons accurately evaluate
      glenoid version preoperatively with reduced workload and expense.

PMID- 29331572
TI  - Comments on "Low-dose-rate prostate brachytherapy: 4-8 week postimplant prostate
      specific antigen a novel predictor of biochemical failure-free survival".

PMID- 29331573
TI  - Deformable image registration-based contour propagation yields clinically
      acceptable plans for MRI-based cervical cancer brachytherapy planning.
AB  - PURPOSE: To study the dosimetric impact of deformable image registration-based
      contour propagation on MRI-based cervical cancer brachytherapy planning. METHODS
      AND MATERIALS: High-risk clinical target volume (HRCTV) and organ-at-risk (OAR)
      contours were delineated on MR images of 10 patients who underwent ring and
      tandem brachytherapy. A second set of contours were propagated using a
      commercially available deformable registration algorithm. "Manual-contour" and
      "propagated-contour" plans were optimized to achieve a maximum dose to the most
      minimally exposed 90% of the volume (D90) (%) of 6 Gy/fraction, respecting
      minimum dose to the most exposed 2cc of the volume (D2cc) OAR constraints of 5.25
      Gy and 4.2 Gy/fraction for bladder and rectum/sigmoid (86.5 and 73.4 Gy
      equivalent dose in 2 Gy fractions [EQD2] for external beam radiotherapy [EBRT] +
      brachytherapy, respectively). Plans were compared using geometric and dosimetric
      (total dose [EQD2] EBRT + brachytherapy) parameters. RESULTS: The differences
      between the manual- and propagated-contour plans with respect to the HRCTV D90
      and bladder, rectum, and sigmoid D2cc were not statistically significant (per
      fraction basis). For the EBRT + brachytherapy course, the D2cc delivered to the
      manually contoured OARs by the propagated-contour plans ranging 98-107%, 95-105%,
      and 92-108% of the dose delivered by the manual-contour plans (max 90.4, 70.3,
      and 75.4 Gy for the bladder, rectum, and sigmoid, respectively). The HRCTV dose
      in the propagated-contour plans was 97-103% of the dose in the manual-contour
      plans (maximum difference 2.92 Gy). Increased bladder filling resulted in
      increased bladder dose in manual- and propagated-contour plans. CONCLUSIONS: When
      deformable image registration-propagated contours are used for cervical
      brachytherapy planning, the HRCTV dose is similar to the dose delivered by manual
      contour plans and the doses delivered to the OARs are clinically acceptable,
      suggesting that our algorithm can replace manual contouring for appropriately
      selected cases that lack major interfractional anatomical changes.

PMID- 29331574
TI  - A Medicare cost analysis of MRI- versus CT-based high-dose-rate brachytherapy of
      the cervix: Can MRI-based planning be less costly?
AB  - PURPOSE: While some institutions deliver multiple fractions per implant for MRI
      based planning, it is common for only one fraction to be delivered per implant
      with CT-based cervical brachytherapy. The purpose of this study was to compare
      physician costs, hospital costs, and overall costs for cervical cancer patients
      treated with either CT-based or MRI-based high-dose-rate (HDR) cervical
      brachytherapy to determine if MRI-based brachytherapy as described can be
      financially feasible. METHODS AND MATERIALS: We identified 40 consecutive
      patients treated with curative intent cervical brachytherapy. Twenty patients
      underwent CT-based HDR brachytherapy with five fractions delivered in five
      implants on nonconsecutive days in an outpatient setting with the first implant
      placed with a Smit sleeve under general anesthesia. Twenty patients received MRI
      based HDR brachytherapy with four fractions delivered in two implants, each with
      MRI-based planning, performed 1-2 weeks apart with an overnight hospital
      admission for each implant. We used Medicare reimbursements to assess physician
      costs, hospital costs, and overall cost. RESULTS: The median cost of MRI-based
      brachytherapy was $14,248.75 (interquartile range [IQR]: $13,421.32-$15,539.74),
      making it less costly than CT-based brachytherapy with conscious sedation (i.e.,
      $18,278.85; IQR: $17,323.13-$19,863.03, p < 0.0001) and CT-based brachytherapy
      with deep sedation induced by an anesthesiologist (i.e., $27,673.44; IQR:
      $26,935.14-$29,511.16, p < 0.0001). CT-based brachytherapy with conscious
      sedation was more costly than CT-based brachytherapy with deep sedation (p <
      0.001). CONCLUSIONS: MRI-based brachytherapy using the described treatment course
      was less costly than both methods of CT-based brachytherapy. Cost does not need
      to be a barrier for MRI-based cervical brachytherapy, especially when delivering
      multiple fractions with the same application.

PMID- 29331575
TI  - Validation of MRI to TRUS registration for high-dose-rate prostate brachytherapy.
AB  - PURPOSE: The objective of this study was to develop and validate an open-source
      module for MRI to transrectal ultrasound (TRUS) registration to support tumor
      targeted prostate brachytherapy. METHODS AND MATERIALS: In this study, 15
      patients with prostate cancer lesions visible on multiparametric MRI were
      selected for the validation. T2-weighted images with 1-mm isotropic voxel size
      and diffusion weighted images were acquired on a 1.5T Siemens imager. Three
      dimensional (3D) TRUS images with 0.5-mm slice thickness were acquired. The
      investigated registration module was incorporated in the open-source 3D Slicer
      platform, which can compute rigid and deformable transformations. An extension of
      3D Slicer, SlicerRT, allows import of and export to DICOM-RT formats. For
      validation, similarity indices, prostate volumes, and centroid positions were
      determined in addition to registration errors for common 3D points identified by
      an experienced radiation oncologist. RESULTS: The average time to compute the
      registration was 35 +/- 3 s. For the rigid and deformable registration,
      respectively, Dice similarity coefficients were 0.87 +/- 0.05 and 0.93 +/- 0.01
      while the 95% Hausdorff distances were 4.2 +/- 1.0 and 2.2 +/- 0.3 mm. MRI
      volumes obtained after the rigid and deformable registration were not
      statistically different (p > 0.05) from reference TRUS volumes. For the rigid and
      deformable registration, respectively, 3D distance errors between reference and
      registered centroid positions were 2.1 +/- 1.0 and 0.4 +/- 0.1 mm while
      registration errors between common points were 3.5 +/- 3.2 and 2.3 +/- 1.1 mm.
      Deformable registration was found significantly better (p < 0.05) than rigid
      registration for all parameters. CONCLUSIONS: An open-source MRI to TRUS
      registration platform was validated for integration in the brachytherapy
      workflow.

PMID- 29331576
TI  - Normative distribution of substance P and its tachykinin neurokinin-1 receptor in
      the medullary serotonergic network of the human infant during postnatal
      development.
AB  - Substance P (SP) and its tachykinin NK1 receptor (NK1R) function within key
      medullary nuclei to regulate cardiorespiratory and autonomic control. We examined
      the normative distribution of SP and NK1R in the serotonergic (5
      Hydroxytryptamine, [5-HT]) network of the human infant medulla during postnatal
      development, to provide a baseline to facilitate future analysis of the SP/NK1R
      system and its interaction with 5-HT within pediatric brainstem disorders in
      early life. [125I] labelled Bolton Hunter SP (BH-SP) tissue receptor
      autoradiography (n = 15), single label immunohistochemistry (IHC) and double
      label immunofluorescence (IF) (n = 10) were used to characterize the normative
      distribution profile of SP and NK1R in the 5-HT network of the human infant
      medulla during postnatal development. Tissue receptor autoradiography revealed
      extensive distribution of SP and NK1R in nuclei intimately related to
      cardiorespiratory function and autonomic control, with significant co
      distribution and co-localization with 5-HT in the medullary network in the normal
      human infant during development. A trend for NK1R binding to decrease with age
      was observed with significantly higher binding in premature and male infants. We
      provide further evidence to suggest a significant role for SP/NK1R in the early
      postnatal period in the modulation of medullary cardiorespiratory and autonomic
      control in conjunction with medullary 5-HT mediated pathways and provide a
      baseline for future analysis of the potential consequences of abnormalities in
      these brainstem neurotransmitter networks during development.

PMID- 29331577
TI  - A novel encystation specific protein kinase regulates chitin synthesis in
      Entamoeba invadens.
AB  - Phosphorylation is an important post-translational modification of proteins and
      is involved in the regulation of a variety of cellular events. The proteome of
      Entamoeba invadens, the reptilian counterpart of Entamoeba histolytica consists
      of an overwhelming number of putative protein kinases, and some may have a role
      to play in Entamoeba encystation. In this study, we have identified a novel
      protein kinase named as EiCSpk (Entamoeba invadenscyst specific protein kinase)
      which expressed almost exclusively during encystation. It is an active Protein
      kinase C with a characteristic substrate phosphorylation and auto-phosphorylation
      property. Gene silencing study has unveiled its role as a regulator of chitin
      synthesis through transcriptional activation of the chitin synthesis pathway
      genes along with glycogen phosphorylases that are involved in the influx of
      glucose from glycogen breakdown for chitin synthesis.

PMID- 29331579
TI  - Corrections.

PMID- 29331578
TI  - Molecular detection and characterisation of Babesia and Theileria in Australian
      hard ticks.
AB  - Babesia and Theileria are intraerythrocytic protozoans of the phylum Apicomplexa.
      These species are capable of infecting wild and domestic animals and have
      historically caused great economic loss in the agricultural industry. In recent
      years human babesiosis has been deemed an emerging zoonosis in North America,
      Europe and Asia. The first locally acquired case of babesiosis in Australia,
      caused by Babesia microti, was reported in March 2012. A number of native Babesia
      and Theileria species have been identified in Australian marsupials, however
      their associated tick vectors and threat to human health is unknown. In the
      present study DNA was extracted from 1154 ticks collected from across Australia.
      PCR was used to amplify a Babesia and Theileria-specific partial region of the
      18S ribosomal RNA gene. Positive samples were sequenced and phylogenetic analysis
      was performed. Twenty-nine sequences were obtained from ticks belonging to the
      genera Ixodes, Haemaphysalis and Bothriocroton. The sequences were closely
      related to Babesia macropus, and Theileria recently identified in marsupials and
      monotremes. Bayesian inference and maximum likelihood methods showed that
      Australian Babesia and Theileria species form monophyletic groups.

PMID- 29331580
TI  - Local delivery of mometasone furoate from an eluting endotracheal tube.
AB  - Laryngeal and tracheal morbidity is a common complication of endotracheal tube
      (ETT)-based airway management, and manifests as local irritation, inflammation,
      and edema. Systemic corticosteroids are commonly administered to manage these
      conditions; however, their efficacy is inadequate and limited by potential severe
      side effects. In the present study, a steroid delivery system for local therapy
      was developed to generate relatively high local drug concentrations and to
      improve drug efficacy. ETTs were coated with electrospun poly (lactic-co-glycolic
      acid) (PLGA) nanofibers loaded with mometasone furoate (MF), creating a
      microscale thick layer. MF exhibited sustained release from coated ETTs over
      14days in vitro. An in vivo efficacy study in rats demonstrated the therapeutic
      benefit of MF-coated ETTs over bare ETTs, as measured by reduced laryngeal
      mucosal thickness and submucosal laryngeal edema. The fiber coating remained
      intact during tube intubation and extubation, demonstrating good adhesion to the
      tubes even after 24h in aqueous solution at 37 degrees C. These findings
      demonstrate the potential of drug-loaded ETTs to revolutionize the standard of
      care for endotracheal intubation.

PMID- 29331581
TI  - Identification and characterization of arginine finger-like motifs, and endosome
      lysosome basolateral sorting signals within the Coxiella burnetii type IV
      secreted effector protein CirA.
AB  - Coxiella burnetii is an obligate intracellular pathogen that replicates in an
      endolysosome-like compartment termed the Coxiella-containing vacuole (CCV).
      Formation of this unique replicative niche requires delivery of bacterial
      effector proteins into the host cytosol where they mediate crucial interactions
      with the host. We previously identified an essential Dot/Icm effector, CirA that
      is required for intracellular replication and CCV formation. Furthermore, CirA
      was shown to stimulate the GTPase activity of RhoA in vitro. In the current
      study, we used a bioinformatics-guided approach and identified three arginine
      finger-like motifs, often found in Rho GTPase-activating proteins (GAPs) and
      endosome-lysosome basolateral sorting signals associated with vesicle
      trafficking. When expressed in mammalian cells, mutation of either endosome
      lysosome-basolateral sorting signals or the arginine finger-like motifs rescued
      stress phenotypes and decreased plasma membrane localization of ectopically
      expressed CirA. We further demonstrate that endosome-lysosome sorting signals are
      required for co-localization with Rab5 and Rab7. Collectively our data indicate
      that arginine finger-like motifs and endosome-lysosome-basolateral sorting
      signals within CirA are essential for interaction with the host cytoskeleton.

PMID- 29331582
TI  - Inositol polyphosphates contribute to cellular circadian rhythms: Implications
      for understanding lithium's molecular mechanism.
AB  - Most living organisms maintain cell autonomous circadian clocks that synchronize
      critical biological functions with daily environmental cycles. In mammals, the
      circadian clock is regulated by inputs from signaling pathways including glycogen
      synthase kinase 3 (GSK3). The drug lithium has actions on GSK3, and also on
      inositol metabolism. While it is suspected that lithium's inhibition of GSK3
      causes rhythm changes, it is not known if inositol polyphosphates can also affect
      the circadian clock. We examined whether the signaling molecule inositol
      hexaphosphate (IP6) has effects on circadian rhythms. Using a bioluminescent
      reporter (Per2::luc) to measure circadian rhythms, we determined that IP6
      increased rhythm amplitude and shortened period in NIH3T3 cells. The IP6 effect
      on amplitude was attenuated by selective siRNA knockdown of GSK3B and
      pharmacological blockade of AKT kinase. However, unlike lithium, IP6 did not
      induce serine-9 phosphorylation of GSK3B. The synthesis of IP6 involves the
      enzymes inositol polyphosphate multikinase (IPMK) and inositol pentakisphosphate
      2-kinase (IPPK). Knockdown of Ippk had effects opposite to those of IP6,
      decreasing rhythm amplitude and lengthening period. Ipmk knockdown had few
      effects on rhythm alone, but attenuated the effects of lithium on rhythms.
      However, lithium did not change the intracellular content of IP6 in NIH3T3 cells
      or neurons. Pharmacological inhibition of the IP6 kinases (IP6K) increased rhythm
      amplitude and shortened period, suggesting secondary effects of inositol
      pyrophosphates may underlie the period shortening effect, but not the amplitude
      increasing effect of IP6. Overall, we conclude that inositol phosphates, in
      particular IP6 have effects on circadian rhythms. Manipulations affecting IP6 and
      related inositol phosphates may offer a novel means through which circadian
      rhythms can be regulated.

PMID- 29331583
TI  - Importins alpha and beta signaling mediates endothelial cell inflammation and
      barrier disruption.
AB  - Nucleocytoplasmic shuttling via importins is central to the function of
      eukaryotic cells and an integral part of the processes that lead to many human
      diseases. In this study, we addressed the role of alpha and beta importins in the
      mechanism of endothelial cell (EC) inflammation and permeability, important
      pathogenic features of many inflammatory diseases such as acute lung injury and
      atherosclerosis. RNAi-mediated knockdown of importin alpha4 or alpha3 each
      inhibited NF-kappaB activation, proinflammatory gene (ICAM-1, VCAM-1, and IL-6)
      expression, and thereby endothelial adhesivity towards HL-60 cells, upon thrombin
      challenge. The inhibitory effect of alpha4 and alpha3 knockdown was associated
      with impaired nuclear import and consequently, DNA binding of RelA/p65 subunit of
      NF-kappaB and occurred independently of IkappaBalpha degradation. Intriguingly,
      knockdown of importins alpha4 and alpha3 also inhibited thrombin-induced RelA/p65
      phosphorylation at Ser536, showing a novel role of alpha importins in regulating
      transcriptional activity of RelA/p65. Similarly, knockdown of importin beta1, but
      not beta2, blocked thrombin-induced activation of RelA/p65 and its target genes.
      In parallel studies, TNFalpha-mediated inflammatory responses in EC were
      refractory to knockdown of importins alpha4, alpha3 or beta1, indicating a
      stimulus-specific regulation of RelA/p65 and EC inflammation by these importins.
      Importantly, alpha4, alpha3, or beta1 knockdown also protected against thrombin
      induced EC barrier disruption by inhibiting the loss of VE-cadherin at adherens
      junctions and by regulating actin cytoskeletal rearrangement. These results
      identify alpha4, alpha3 and beta1 as critical mediators of EC inflammation and
      permeability associated with intravascular coagulation.

PMID- 29331585
TI  - Cathepsin L promotes ionizing radiation-induced U251 glioma cell migration and
      invasion through regulating the GSK-3beta/CUX1 pathway.
AB  - Cathepsin L (CTSL) is a lysosomal cysteine protease overexpressed and secreted by
      tumor cells. Our previous study found that CTSL was involved in ionizing
      radiation (IR)-induced epithelial-mesenchymal transition (EMT) and the increase
      of glioma invasion and migration. However, the mechanisms by which CTSL promoted
      this IR-induced glioma migration and invasion remained unclear. In this study, we
      demonstrated that IR reduced glycogen synthase kinase-3beta (GSK-3beta) activity,
      via the CTSL-mediated phosphorylation of its serine-9 residue, in U251 cells.
      Moreover, inhibition of p-GSK-3betaSer9 in overexpressing CTSL cells attenuated
      EMT and decreased the expression of snail, an EMT-related transcription factor.
      As a result, U251 cell migration and invasion was inhibited compared to over-CTSL
      cells. Alternatively, when CTSL was activated by IR or exogenously overexpressed,
      CTSL promoted EMT by processing homeobox protein cut-like1 (CUX1) to produce the
      physiologically active p110 isoform. In brief, this study revealed that IR
      induced EMT as well as migration and invasion of glioma cells are mediated by
      CTSL through the Akt/GSK-3beta/snail and CUX1 pathways. Consequently, this
      research also led to the identification of a potential novel target for
      therapeutic intervention of glioma.

PMID- 29331586
TI  - Positive effects of total recovery period on anti- and pro-inflammatory cytokines
      are not linked to performance re-establishment in overtrained mice.
AB  - The association between excessive training sessions (i.e., overtraining/OT) and
      periods of inadequate recovery is linked to the nonfunctional overreaching (NFOR)
      state, which is defined as an unexplained decrement or stagnation of performance.
      The cytokine hypothesis of OT considers that pro-inflammatory cytokines are
      responsible by the NFOR state-induced performance decrement. Investigations using
      rodent models of OT verified increased levels of pro-inflammatory cytokines in
      hypothalamus, liver, serum and skeletal muscle samples. Recently, our research
      group observed that a 2-week total recovery period was not able to re-establish
      the NFOR state-induced performance decrement. As the responses of anti- and pro
      inflammatory cytokines were not measured, we aimed to investigate the effects of
      2-week total recovery period on the protein contents of IL-1beta, IL-6, IL-10, IL
      15, TNF-alpha and SOCS-3 in serum and skeletal muscle samples of overtrained
      mice. Also, a bioinformatics analysis was performed to investigate the
      correlations of IL-1beta, IL-6, IL-10, IL-15, TNF-alpha and SOCS-3 in skeletal
      muscle with locomotor activity. In summary, the 2-week total recovery period
      upregulated the anti-inflammatory cytokines and normalized the pro-inflammatory
      cytokines without a concomitant re-establishment of performance.

PMID- 29331587
TI  - IL-23/IL-17 immune axis in Guillain Barre Syndrome: Exploring newer vistas for
      understanding pathobiology and therapeutic implications.
AB  - Guillain Barre Syndrome (GBS) is a severe disorder of the peripheral nervous
      system with an inadequately known etiopathology. It is a post infectious immune
      mediated disorder, characterized by autoantibody production, complement
      activation as well as T reactivity against gangliosides. However, the precise
      etiopathogenesis remains poorly understood in a majority of the patients. Th17
      cells, a recently identified lineage of Th cells have emerged as a predominant
      inducer of autoimmunity and inflammation in various immunological disorders.
      Pathobiological role of Th17 pathway is also becoming increasingly apparent in
      the nervous system disorders. Two cytokines, such as IL-23, known to determine
      the pathogenic potential of Th17 cells and IL-17, a prototype effector cytokine
      of Th17 pathway can form IL-23/IL-17 immune axis. Aberrant functioning of this
      immune axis has been implicated in many autoimmune diseases. Therapeutic
      strategies that potentially target this immune axis have shown encouraging
      results in diseases with immunological underpinnings. Preliminary data obtained
      both from animal and clinical studies indicate a possible role of this immune
      axis in GBS. Herein, we explore and highlight the relevance and functional
      implications of IL-23/IL-17 immune axis in GBS. Understanding this immune axis
      may shed important insights into the etiology and treatment of GBS.

PMID- 29331588
TI  - Antagonism of cysteinyl leukotriene receptor 1 (cysLTR1) by montelukast
      suppresses cell senescence of chondrocytes.
AB  - Aging is closely associated with osteoarthritis (OA). Although its underlying
      mechanisms remain unknown, cellular senescence in chondrocytes has become an
      important therapeutic target for the treatment of OA. Cysteinyl leukotriene
      receptors (cysLTRs) mediate the pathobiological function of cysteinyl
      leukotrienes (cysLTs). However, the roles of cysLTRs in the pathogenesis of OA
      have not been reported before. In the current study, we found that cysLTR1 but
      not cysLTR2 is expressed in human primary chondrocytes. In addition, stimulation
      with tumor necrosis factor alpha (TNF-alpha) resulted in a significant increase
      in the expression of cysLTR1. Interestingly, montelukast, a specific cysLTR1
      antagonist, attenuated TNF-alpha-induced up-regulation of the activity of
      senescence-associated beta-galactosidase (SA-beta-Gal). In addition, TNF-alpha
      led to cell cycle arrest at the G0/G1 phase, which was prevented by treatment
      with montelukast. Notably, montelukast reduced expression of the senescence
      markers p53, p21 and PAI-1. In addition, montelukast ameliorated TNF-alpha
      induced K382 acetylation of p53 by promoting the expression of SIRT1. Silencing
      of SIRT1 using SIRT1 siRNA broke the inhibitory effects of montelukast on K382
      acetylation of p53. Importantly, silencing of cysLTR1 reversed the reduction of
      SIRT1 expression as well as the K382 acetylation of p53. Our findings strongly
      implicate that cysLTR1 has the capacity to regulate cellular senescence in
      chondrocytes. It is suggested that montelukast may be a potential therapeutic
      agent for chondro-protective therapy.

PMID- 29331584
TI  - Protein neddylation and its alterations in human cancers for targeted therapy.
AB  - Neddylation, a post-translational modification that conjugates an ubiquitin-like
      protein NEDD8 to substrate proteins, is an important biochemical process that
      regulates protein function. The best-characterized substrates of neddylation are
      the cullin subunits of Cullin-RING ligases (CRLs), which, as the largest family
      of E3 ubiquitin ligases, control many important biological processes, including
      tumorigenesis, through promoting ubiquitylation and subsequent degradation of a
      variety of key regulatory proteins. Recently, increasing pieces of experimental
      evidence strongly indicate that the process of protein neddylation modification
      is elevated in multiple human cancers, providing sound rationale for its
      targeting as an attractive anticancer therapeutic strategy. Indeed, neddylation
      inactivation by MLN4924 (also known as pevonedistat), a small molecule inhibitor
      of E1 NEDD8-activating enzyme currently in phase I/II clinical trials, exerts
      significant anticancer effects by inducing cell cycle arrest, apoptosis,
      senescence and autophagy in a cell-type and context dependent manner. Here, we
      summarize the latest progresses in the field with a major focus on preclinical
      studies in validation of neddylation modification as a promising anticancer
      target.

PMID- 29331589
TI  - The iridocorneal endothelial syndrome.
AB  - The iridocorneal endothelial syndrome represents a unique group of ocular
      pathologies (Chandler syndrome, progressive iris atrophy, and Cogan-Reese
      syndrome) characterized by the proliferation of corneal endothelial cells that
      migrate toward the iridocorneal angle and iris surface causing, to a degree
      varying according to the subtype, corneal edema and decompensation and secondary
      glaucoma, whether by obstructing the angle or producing peripheral anterior
      synechiae by contraction of the basement membrane of the migrating cells over the
      surface of the iris. A triggering factor, possibly viral, induces the corneal
      endothelial cells to proliferate and behave like epithelial cells. Diagnosis is
      made based on typical ocular findings on the cornea and iris. Iridocorneal
      endothelial syndrome is more frequent in young women, with unilateral involvement
      in most cases. In vivo confocal microscopy is an excellent diagnostic tool,
      especially in borderline presentations like early cases of Chandler syndrome,
      which affects the cornea predominantly. Typical clinical management consists of
      treating the corneal edema and decompensation, where endothelial keratoplasty
      techniques have replaced in many cases the need for a penetrating keratoplasty
      and treating the secondary glaucoma, which usually requires surgical
      intervention.

PMID- 29331590
TI  - Setting mechanism of a new injectable Dicalcium Phosphate Dihydrate (DCPD)
      forming cement.
AB  - We previously described the gelation mechanism of calcium polyphosphate (CPP) in
      the presence of water. In this study, we developed novel and injectable poly
      dicalcium phosphate dihydrate (P-DCPD) forming cement by the reaction of acidic
      CPP gel with alkali tetracalcium phosphate (TTCP). The setting reaction mechanism
      of P-DCPD is due to the intermolecular interaction between CPP gel and TTCP that
      was supported by XRD, AFM, Raman spectra analysis and SEM. The setting mechanism
      of P-DCPD is completely different from the classical calcium phosphate cement
      (CPC) that achieves crystallization by monophosphates reaction. P-DCPD represents
      a new type of poly-CPCs with significant advantages, including strong mechanical
      strength, excellent cohesion and easy of handling. More extensive experiments are
      currently underway to further evaluate the performance of P-DCPD cements,
      including biocompatibility, degradation behavior and bone defect hearing
      efficacy, among others.

PMID- 29331593
TI  - Latent class analysis of the health of the nation outcome scales: A comparison of
      Swiss and English profiles and exploration of their predictive utility.

PMID- 29331592
TI  - Combined creatinine-cystatin C CKD-EPI equation significantly underestimates
      measured glomerular filtration rate in people with type 2 diabetes mellitus.
AB  - AIM: To evaluate the accuracy of creatinine and cystatin C (cysC) equations to
      estimate glomerular filtration rate (GFR) in type 2 diabetes mellitus (DM)
      patients and healthy adults. METHODS: Case-control study including 84 patients
      with type 2 DM and 100 healthy adults with measured GFR (mGFR)>=60mL/min/1.73m2.
      GFR was measured by 51Cr-EDTA and estimated (eGFR) by the following equations
      using creatinine, cysC or both markers: Chronic Kidney Disease Epidemiology
      Collaboration (CKD-EPI), Caucasian Asian Pediatrics and Adults (CAPA), CKD-EPI
      creatinine-cystatin C (CKDEPI-CC), and CKD-EPI cystatin C (CKDEPIcysC). Agreement
      was evaluated by Bland & Altman analysis. RESULTS: Healthy individuals were 66%
      females, aged 38+/-14years; they presented mGFR 112+/-19mL/min/1.73m2 and eGFR by
      CKD-EPI, CKDEPI-CC, CKDEPIcysC and CAPA equations, respectively, 108+/-17, 102+/
      15, 97+/-16 and 93+/-16mL/min/1.73m2. DM group were 50% females, aged 59+/
      19years and presented mGFR 104+/-27 and eGFR 87+/-19, 80+/-18, 74+/-20 and 73+/
      18mL/min/1.73m2, respectively. All equations significantly underestimated mGFR,
      excepting creatinine-based CKD-EPI in the healthy group. The performance was
      considerably worse for GFRs above 120mL/min/1.73m2. CONCLUSION: In both healthy
      and type 2 DM patients, cystatin C-based equations, including the combined CKD
      EPI creatinine-cystatin equation, failed to improve the accuracy of GFR
      estimation, especially for normal and high normal GFR values.

PMID- 29331591
TI  - Brochosomins and other novel proteins from brochosomes of leafhoppers (Insecta,
      Hemiptera, Cicadellidae).
AB  - Brochosomes (BS) are secretory granules resembling buckyballs, produced
      intracellularly in specialized glandular segments of the Malpighian tubules and
      forming superhydrophobic coatings on the integuments of leafhoppers (Hemiptera,
      Cicadellidae). Their composition is poorly known. Using a combination of SDS
      PAGE, LC-MS/MS, next-generation sequencing (RNAseq) and bioinformatics we
      demonstrate that the major structural component of BS of the leafhopper
      Graphocephala fennahi Young is a novel family of 21-40-kDa secretory proteins,
      referred to herein as brochosomins (BSM), apparently cross-linked by disulfide
      bonds. At least 28 paralogous BSM were identified in a transcriptome assembly of
      this species, most of which were detected in BS. Multiple additional BS
      associated proteins (BSAP), possibly loosely attached to the outer and inner
      surfaces of BS, were also identified; some of these were glycine-, tyrosine- and
      proline-rich. BSM and BSAP together accounted for half of the 100 most expressed
      transcripts in the Malpighian tubules of G. fennahi. Except for several minor
      BSAP possibly related to cyclases, BSM and BSAP had no homologs among known
      proteins, thus representing taxonomically restricted gene families (orphans).
      Searching in 50 whole-body transcriptome assemblies of Hemiptera found homologs
      of BSM in representatives of all five families of the superfamily Membracoidea
      (Cicadellidae, Myerslopiidae, Aetalionidae, Membracidae, and Melizoderidae), but
      not in other lineages. Among the identified proteins only BSM were shared in
      common between all 17 surveyed leafhoppers known to produce BS. Combined CHN
      elemental and aminoacid analyses estimated the total protein content of BS from
      the integument of G. fennahi to be 60-70%.

PMID- 29331594
TI  - Effects of physical activity on the symptoms of Tourette syndrome: A systematic
      review.
AB  - There is irrefutable evidence that routine physical activity or exercise can
      offer considerable health benefits to individuals living with various mental
      disorders. However, it is not clear what effect physical activity has on the
      symptoms of Tourette syndrome. Despite a paucity of evidence, physical activity
      or exercise has already been recommended by various health organizations for the
      management of tics. We provide a systematic review of the effects of physical
      activity or exercise on tic symptomology in individuals with Tourette syndrome.
      Major electronic databases were searched for all available publications before
      August 2017. Keywords and MeSH terms included "physical activity" or "exercise"
      or "exercise therapy" or "physical exertion" or "sports" and "tics" or "tic
      disorders" or "Tourette." Eight studies were included, the majority of which were
      case reports. Despite a number of methodological limitations of the included
      studies, the review points to a trend that the effects of acute physical activity
      are intensity-dependent, where light intensity may alleviate and vigorous
      intensity may exacerbate tics. Chronic physical activity, however, appears to
      reduce the severity of tics even at higher intensity. Several physiological
      mechanisms may explain the differential effects of acute and chronic physical
      activity in Tourette syndrome. Future randomized controlled studies should better
      characterize the effects of different intensities and types of physical activity
      in Tourette syndrome.

PMID- 29331595
TI  - The interaction between neurocognitive functioning, subthreshold psychotic
      symptoms and pharmacotherapy in 22q11.2 deletion syndrome: A longitudinal
      comparative study.
AB  - BACKGROUND: The 22q11.2 deletion syndrome (22q11DS) is the most common genetic
      syndrome associated with schizophrenia. The goal of this study was to evaluate
      longitudinally the interaction between neurocognitive functioning, the presence
      of subthreshold psychotic symptoms (SPS) and conversion to psychosis in
      individuals with 22q11DS. In addition, we attempted to identify the specific
      neurocognitive domains that predict the longitudinal evolution of positive and
      negative SPS, as well as the effect of psychiatric medications on 22q11DS
      psychiatric and cognitive developmental trajectories. METHODS: Forty-four
      participants with 22q11DS, 19 with Williams syndrome (WS) and 30 typically
      developing (TD) controls, age range 12-35years, were assessed at two time points
      (15.2+/-2.1months apart). Evaluation included the Structured Interview for
      Prodromal Symptoms (SIPS), structured psychiatric evaluation and the Penn
      Computerized Neurocognitive Battery (CNB). RESULTS: 22q11DS individuals with SPS
      had a yearly conversion rate to psychotic disorders of 8.8%, compared to none in
      both WS and TD controls. Baseline levels of negative SPS were associated with
      global neurocognitive performance (GNP), executive function and social cognition
      deficits, in individuals with 22q11DS, but not in WS. Deficits in GNP predicted
      negative SPS in 22q11DS and the emergence or persistence of negative SPS. 22q11DS
      individuals treated with psychiatric medications showed significant improvement
      in GNP score between baseline and follow-up assessments, an improvement that was
      not seen in untreated 22q11DS. CONCLUSIONS: Our results highlight the time
      dependent interplay among positive and negative SPS symptoms, neurocognition and
      pharmacotherapy in the prediction of the evolution of psychosis in 22q11DS.

PMID- 29331596
TI  - Problem-solving therapy for adult depression: An updated meta-analysis.
AB  - BACKGROUND: Problem-solving therapy (PST) is one of the best examined types of
      psychotherapy for adult depression. No recent meta-analysis has examined the
      effects of PST compared to control groups or to other treatments. We wanted to
      verify whether PST is effective, whether effects are comparable to those of other
      treatments, and whether we could identify the possible sources of high
      heterogeneity that was found in earlier meta-analyses. METHODS: We conducted
      systematic searches in bibliographical databases, including PubMed, PsycInfo,
      Embase and the Cochrane database of randomized trials. RESULTS: We included 30
      randomized controlled trials on PST (with 3530 patients), in which PST was
      compared to control conditions, with other therapies, and with pharmacotherapy.
      We could compare these 30 trials on PST also with 259 trials on other
      psychotherapies for adult depression. The effect size of PST versus control
      groups was g=0.79 (0.57-1.01) with very high heterogeneity (I2=84; 95% CI: 77
      88). The effect size from the 9 studies with low risk of bias was g=0.34 (95% CI:
      0.22-0.46) with low heterogeneity (I2=32; 95% CI: 0-68), which is comparable to
      the effects of other psychotherapies. PST was a little more effective than other
      therapies in direct comparisons, but that may be explained by the considerable
      number of studies with researcher allegiance towards PST. In meta-regression
      analyses of all controlled studies, no significant difference between PST and
      other therapies was found. CONCLUSION: PST is probably an effective treatment for
      depression, with effect sizes that are small, but comparable to those found for
      other psychological treatments of depression.

PMID- 29331597
TI  - Variation of genes involved in oxidative and nitrosative stresses in depression.
AB  - The dominating hypothesis among numerous hypotheses explaining the pathogenesis
      of depressive disorders (DD) is the one involving oxidative and nitrosative
      stress. In this study, we examined the association between single-nucleotide
      polymorphisms of the genes encoding SOD2 (superoxide dismutase 2), CAT
      (catalase), GPx4 (glutathione peroxidase 4), NOS1 (nitric oxide synthase 1), NOS2
      (nitric oxide synthase 2), and the development of depressive disorders. Our study
      was carried out on the DNA isolated from peripheral blood collected from 281
      depressed patients and 229 controls. Using TaqMan probes, we genotyped the
      following six polymorphisms: c.47T>C (p.Val16Ala) (rs4880) in SOD2, c.-89A>T
      (rs7943316) in CAT, c.660T>C (rs713041) in GPx4, c.-420-34221G>A (rs1879417) in
      NOS1, c.1823C>T (p.Ser608Leu) (rs2297518), and c.-227G>C (rs10459953) in NOS2. We
      found that the T/T genotype of the c.47T>C polymorphism was linked with an
      increased risk of depression. Moreover, the T/T genotype and T allele of c.660T>C
      increased the risk of DD occurrence, while the heterozygote and C allele
      decreased this risk. On the other hand, we discovered that the A/A genotype of c.
      89A>T SNP was associated with a reduced risk of DD, while the A/T genotype
      increased this risk. We did not find any correlation between the
      genotypes/alleles of c.-420-34221G>A, c.1823C>T, and c.-227G>C, and the
      occurrence of DD. In addition, gene-gene and haplotype analyses revealed that
      combined genotypes and haplotypes were connected with the disease. Moreover, we
      found that sex influenced the impact of some SNPs on the risk of depression.
      Concluding, the studied polymorphisms of SOD2, CAT and GPx4 may modulate the risk
      of depression. These results support the hypothesis that oxidative and
      nitrosative stresses are involved in the pathogenesis of depressive disorders.

PMID- 29331598
TI  - Commentary on "Motor system dysfunction in the schizophrenia diathesis: Neural
      systems to neurotransmitters".

PMID- 29331599
TI  - Long-term reduction of seclusion and forced medication on a hospital-wide level:
      Implementation of an open-door policy over 6 years.
AB  - BACKGROUND: Psychiatric inpatient treatment is increasingly performed in settings
      with locked doors. However, locked wards have well-known disadvantages and are
      ethically problematic. In addition, recent data challenges the hypothesis that
      locked wards provide improved safety over open-door settings regarding suicide,
      absconding and aggression. Furthermore, there is evidence that the introduction
      of an open-door policy may lead to short-term reductions in involuntary measures.
      The aim of this study was to assess if the introduction of an open-door policy is
      associated with a long-term reduction of the frequency of seclusion and forced
      medication. METHOD: In this 6-year, hospital-wide, longitudinal, observational
      study, we examined the frequency of seclusion and forced medication in 17,359
      inpatient cases admitted to the Department of Adult Psychiatry, Universitare
      Psychiatrische Kliniken (UPK) Basel, University of Basel, Switzerland. In an
      approach to enable a less restrictive policy, six previously closed psychiatric
      wards were permanently opened beginning from August 2011. During this process, a
      systematic change towards a more patient-centered and recovery-oriented care was
      applied. Statistical analysis consisted of generalized estimating equations (GEE)
      models. RESULTS: In multivariate analyses controlling for potential confounders,
      the implementation of an open-door policy was associated with a continuous
      reduction of seclusion (from 8.2 to 3.5%; etap2=0.82; odds ratio: 0.88) and
      forced medication (from 2.4 to 1.2%; etap2=0.70; odds ratio: 0.90). CONCLUSION:
      This underlines the potential of the introduction of an open-door policy to
      attain a long-term reduction in involuntary measures.

PMID- 29331600
TI  - A real world study on the genetic, cognitive and psychopathological differences
      of obese patients clustered according to eating behaviours.
AB  - BACKGROUND: Considering that specific genetic profiles, psychopathological
      conditions and neurobiological systems underlie human behaviours, the phenotypic
      differentiation of obese patients according to eating behaviours should be
      investigated. The aim of this study was to classify obese patients according to
      their eating behaviours and to compare these clusters in regard to
      psychopathology, personality traits, neurocognitive patterns and genetic
      profiles. METHODS: A total of 201 obese outpatients seeking weight reduction
      treatment underwent a dietetic visit, psychological and psychiatric assessment
      and genotyping for SCL6A2 polymorphisms. Eating behaviours were clustered through
      two-step cluster analysis, and these clusters were subsequently compared.
      RESULTS: Two groups emerged: cluster 1 contained patients with predominantly
      prandial hyperphagia, social eating, an increased frequency of the long allele of
      the 5-HTTLPR and low scores in all tests; and cluster 2 included patients with
      more emotionally related eating behaviours (emotional eating, grazing, binge
      eating, night eating, post-dinner eating, craving for carbohydrates),
      dysfunctional personality traits, neurocognitive impairment, affective disorders
      and increased frequencies of the short (S) allele and the S/S genotype.
      CONCLUSIONS: Aside from binge eating, dysfunctional eating behaviours were useful
      symptoms to identify two different phenotypes of obese patients from a
      comprehensive set of parameters (genetic, clinical, personality and
      neuropsychology) in this sample. Grazing and emotional eating were the most
      important predictors for classifying obese patients, followed by binge eating.
      This clustering overcomes the idea that 'binging' is the predominant altered
      eating behaviour, and could help physicians other than psychiatrists to identify
      whether an obese patient has an eating disorder. Finally, recognising different
      types of obesity may not only allow a more comprehensive understanding of this
      illness, but also make it possible to tailor patient-specific treatment pathways.

PMID- 29331601
TI  - Predictors of length of stay in psychiatric inpatient units: Does their effect
      vary across countries?
AB  - BACKGROUND: Previous studies in individual countries have identified inconsistent
      predictors of length of stay (LoS) in psychiatric inpatient units. This may
      reflect methodological inconsistencies across studies or true differences of
      predictors. In this study we assessed predictors of LoS in five European
      countries and explored whether their effect varies across countries. METHODS:
      Prospective cohort study. All patients admitted over 14 months to 57 psychiatric
      inpatient units in Belgium, Germany, Italy, Poland and United Kingdom were
      screened. Putative predictors were collected from medical records and in face-to
      face interviews and tested for their association with LoS. RESULTS: Average LoS
      varied from 17.9days in Italy to 55.1days in Belgium. In the overall sample being
      homeless, receiving benefits, social isolation, diagnosis of psychosis, greater
      symptom severity, substance use, history of previous admission and being
      involuntarily admitted predicted longer LoS. Several predictors showed
      significant interaction effects with countries in predicting LoS. One variable,
      homelessness, predicted a different LoS even in opposite directions, whilst for
      other predictors the direction of the association was the same, but the strength
      of the association with LoS varied across countries. CONCLUSIONS: The same
      patient characteristics have a different impact on LoS in different contexts.
      Thus, although some predictor variables related to clinical severity and social
      dysfunction appear of generalisable relevance, national studies on LoS are
      required to understand the complex influence of different patient characteristics
      on clinical practice in the given contexts.

PMID- 29331602
TI  - A cross-continental analysis of weight gain, psychiatric diagnoses and medication
      use during inpatient psychiatric treatment. The international study on physical
      illness in mentally ill.
AB  - Weight gain among psychiatric inpatients is a widespread phenomenon. This change
      in body mass index (BMI) can be caused by several factors. Based on recent
      research, we assume the following factors are related to weight gain during
      psychiatric inpatient treatment: psychiatric medication, psychiatric diagnosis,
      sex, age, weight on admission and geographic region of treatment. 876 of
      originally recruited 2328 patients met the criteria for our analysis. Patients
      were recruited and examined in mental health care centres in Nigeria (N = 265),
      Japan (N = 145) and Western-Europe (Denmark, Germany and Switzerland; N = 466).
      There was a significant effect of psychiatric medication, psychiatric diagnoses
      and geographic region, but not age and sex, on BMI changes. Geographic region had
      a significant effect on BMI change, with Nigerian patients gaining significantly
      more weight than Japanese and Western European patients. Moreover, geographic
      region influenced the type of psychiatric medication prescribed and the
      psychiatric diagnoses. The diagnoses and psychiatric medication prescribed had a
      significant effect on BMI change. In conclusion, we consider weight gain as a
      multifactorial phenomenon that is influenced by several factors. One can discuss
      a number of explanations for our findings, such as different clinical practices
      in the geographical regions (prescribing or admission strategies and access-to
      care aspects), as well as socio-economic and cultural differences.

PMID- 29331603
TI  - Metabolic risk factors in schizophrenia and bipolar disorder: The effect of
      comedication with selective serotonin reuptake inhibitors and antipsychotics.
AB  - BACKGROUND: The aim of this observational study was to investigate the
      relationship between metabolic factors and use of selective serotonin reuptake
      inhibitors (SSRIs) combined with olanzapine, quetiapine or risperidone. METHODS:
      Data from the Norwegian Thematically Organized Psychosis study, a cross-sectional
      study on 1301 patients with schizophrenia (n=868) or bipolar disorder (n=433),
      were analyzed. As exposure variables in the linear regression model were included
      the dose or serum concentration of SSRIs (n=280) and of olanzapine (n=398),
      quetiapine (n=234) or risperidone (n=128). The main outcome variables were levels
      of total cholesterol, low and high density lipoprotein (LDL and HDL) cholesterol,
      triglycerides and glucose. RESULTS: One defined daily dose (DDD) per day of an
      SSRI in addition to olanzapine was associated with an increase in total
      cholesterol of 0.16 (CI 0.01 to 0.32) mmol/L (P=0.042) and an increase in LDL
      cholesterol of 0.17 (CI 0.02 to 0.31) mmol/L (P=0.022). An SSRI serum
      concentration in the middle of the reference interval in addition to quetiapine
      was associated with an increase in total cholesterol of 0.39 (CI 0.10 to 0.68)
      mmol/L (P=0.011) and an increase in LDL-cholesterol of 0.29 (0.02 to 0.56) mmol/L
      (P=0.037). There were no such effects when combined with risperidone.
      CONCLUSIONS: The findings indicate only minor deteriorations of metabolic
      variables associated with treatment with an SSRI in addition to olanzapine and
      quetiapine, and none when combined with risperidone. These results suggest that
      SSRIs can be used in combination with antipsychotics, and that the possible
      increase in cardiovascular risk is negligible.

PMID- 29331606
TI  - Editorial.

PMID- 29331604
TI  - Efficacy of intravenous lidocaine on pain relief in patients undergoing
      laparoscopic cholecystectomy: A meta-analysis from randomized controlled trials.
AB  - OBJECTIVE: Whether intravenous lidocaine has a beneficial role in controlling
      acute pain after a laparoscopic cholecystectomy (LC) in currently unknown. We
      performed a meta-analysis from randomized controlled trials (RCTs) to determine
      the efficacy and safety of intravenous lidocaine for the treatment of acute
      postoperative pain after LC. METHODS: In November 2017, a systematic search was
      performed in PubMed, EMBASE, Web of Science, ScienceDirect, and the Cochrane
      Library. RCTs comparing lidocaine and placebo in patients undergoing LC were
      retrieved. The primary endpoint was the visual analogue scale (VAS) score and
      opioid requirements at 12 h, 24 h and 48 h. The secondary endpoint was the length
      of hospital stay and opioid-related adverse effect. Stata 12.0 was used for the
      data analysis. RESULTS: Finally, six RCTs were included in the meta-analysis.
      Results indicated that intravenous lidocaine was associated with reduced pain
      scores and cumulative opioid consumption at 12 h, 24 h, and 48 h following a LC.
      Similarly, lidocaine was associated with a reduction in the incidence of nausea
      and vomiting, ileus and pruritus. CONCLUSION: Intravenous use of lidocaine was
      able to reduce acute postoperative pain, total opioid requirements and opioid
      related adverse effects following a LC. Further studies should determine whether
      lidocaine has a positive role in improving the postoperative function after a LC.

PMID- 29331607
TI  - Solid dispersions to enhance the delivery of a potential drug candidate LPSF/FZ4
      for the treatment of schistosomiasis.
AB  - Drug candidate LPSF/FZ4 with promising schistosomicidal properties in vitro was
      previously synthesized. However, LPSF/FZ4 has limited aqueous solubility (<1
      MUg/mL), leading to ineffective dissolution and, therefore, no meaningful in vivo
      comparative studies could be pursued. This study was aimed to develop a proper
      amorphous solid dispersion (SD) to enhance the solubility and dissolution rate of
      LPSF/FZ4 such that its biological activity could be investigated. To better
      understand its physiological behavior, the pKa of LPSF/FZ4, a monoprotic weak
      acid with NH group at the imidazolidine ring, was first determined to be 8.13
      using an automated SiriusT3. The development of SD systems for LPSF/FZ4 involved
      the evaluation of various water-soluble polymer carriers such as PVP K-29/32, PVP
      K-90, HPMC K4M, PVPVA 64 and SOLUPLUS(r). The most promising SD systems were
      selected through in vitro dissolution studies under nonsink conditions, together
      with physicochemical characterization as well as accelerated stability study. It
      was shown that SD of 10% LPSF/FZ4 in SOLUPLUS(r) and PVP K-90 could significantly
      increase the area-under-the-curve value of the nonsink dissolution profile (AUC
      values of the SD in SOLUPLUS(r) and PVP K-90 were 1381.03 and 1342.34 MUL/mL.min,
      respectively, and that of the pure crystalline drug was 0.02 MUL/mL.min), a
      useful surrogate for the in vivo bioavailability. Cmax values for the SD in
      SOLUPLUS(r) (12.50 MUL/mL) and PVP K-90 (25.86 MUL/mL) were also higher than the
      one of the crystalline drug (0.02 MUL/mL). The SD system of LPSF/FZ4 in
      SOLUPLUS(r) showed a significant increase in schistosomicidal activity in an
      animal model as compared with the conventional treatment using crystalline drug,
      consistent with the AUC trend from the nonsink dissolution. Thus this SD system
      of LPSF/FZ4 could be useful as a potential formulation for treating
      schistosomiasis.

PMID- 29331608
TI  - Allosteric effects in bacteriophage HK97 procapsids revealed directly from
      covariance analysis of cryo EM data.
AB  - The information content of cryo EM data sets exceeds that of the electron
      scattering potential (cryo EM) density initially derived for structure
      determination. Previously we demonstrated the power of data variance analysis for
      characterizing regions of cryo EM density that displayed functionally important
      variance anomalies associated with maturation cleavage events in Nudaurelia Omega
      Capensis Virus and the presence or absence of a maturation protease in
      bacteriophage HK97 procapsids. Here we extend the analysis in two ways. First,
      instead of imposing icosahedral symmetry on every particle in the data set during
      the variance analysis, we only assume that the data set as a whole has
      icosahedral symmetry. This change removes artifacts of high variance along
      icosahedral symmetry axes, but retains all of the features previously reported in
      the HK97 data set. Second we present a covariance analysis that reveals
      correlations in structural dynamics (variance) between the interior of the HK97
      procapsid with the protease and regions of the exterior (not seen in the absence
      of the protease). The latter analysis corresponds well with hydrogen deuterium
      exchange studies previously published that reveal the same correlation.

PMID- 29331610
TI  - Pseudomonas putida modulates the expression of miRNAs and their target genes in
      response to drought and salt stresses in chickpea (Cicer arietinum L.).
AB  - MicroRNAs are small non-coding regulatory RNA molecules that play an important
      role in the modulation of gene expression during various environmental stresses.
      Pseudomonas putida RA, a plant growth promoting rhizobacteria (PGPR) colonizes
      the root surface of plants improving their growth and development during abiotic
      stresses modulating the expression of stress-responsive genes; however, the
      impact of RA on stress responsive-miRNA remains elusive. The present study was an
      attempt to delineate the role of PGPR in modulating stress responsive-miRNAs in a
      tolerant desi chickpea genotype exposed to drought and salt stresses. The
      existence of variable expression patterns of individual miRNAs and their target
      genes under these stresses at different time points indicate a distinct miRNA
      mediated perception and response mechanisms operating under these stresses in the
      presence or absence of RA in chickpea.

PMID- 29331609
TI  - Structure of the Bacillus anthracis dTDP-l-rhamnose biosynthetic pathway enzyme:
      dTDP-alpha-d-glucose 4,6-dehydratase, RfbB.
AB  - Many bacteria require l-rhamnose as a key cell wall component. This sugar is
      transferred to the cell wall using an activated donor dTDP-l-rhamnose, which is
      produced by the dTDP-l-rhamnose biosynthetic pathway. We determined the crystal
      structure of the second enzyme of this pathway dTDP-alpha-d-glucose 4,6
      dehydratase (RfbB) from Bacillus anthracis. Interestingly, RfbB only crystallized
      in the presence of the third enzyme of the pathway RfbC; however, RfbC was not
      present in the crystal. Our work represents the first complete structural
      characterization of the four proteins of this pathway in a single Gram-positive
      bacterium.

PMID- 29331611
TI  - Resistance to peer influence moderates the relationship between perceived (but
      not actual) peer norms and binge drinking in a college student social network.
AB  - INTRODUCTION: Adolescent and young adult binge drinking is strongly associated
      with perceived social norms and the drinking behavior that occurs within peer
      networks. The extent to which an individual is influenced by the behavior of
      others may depend upon that individual's resistance to peer influence (RPI).
      METHODS: Students in their first semester of college (N=1323; 54.7% female, 57%
      White, 15.1% Hispanic) reported on their own binge drinking, and the perceived
      binge drinking of up to 10 important peers in the first-year class. Using network
      autocorrelation models, we investigated cross-sectional relationships between
      participant's binge drinking frequency and the perceived and actual binge
      drinking frequency of important peers. We then tested the moderating role of RPI,
      expecting that greater RPI would weaken the relationship between perceived and
      actual peer binge drinking on participant binge drinking. RESULTS: Perceived and
      actual peer binge drinking were statistically significant predictors of
      participant binge drinking frequency in the past month, after controlling for
      covariates. RPI significantly moderated the association between perceptions of
      peer binge drinking and participant's own binge drinking; this association was
      weaker among participants with higher RPI compared to those with lower RPI. RPI
      did not interact with the actual binge drinking behavior of network peers.
      CONCLUSIONS: RPI may function to protect individuals from the effect of their
      perceptions about the binge drinking of peers, but not from the effect of the
      actual binge drinking of peers.

PMID- 29331612
TI  - Arterial Spin Labeling Cerebral Perfusion Magnetic Resonance Imaging in Migraine
      Aura: An Observational Study.
AB  - BACKGROUND: Changes in cerebral perfusion during migraine with aura (MA) have
      been assessed mainly using dynamic susceptibility contrast (DSC) magnetic
      resonance perfusion imaging. A contrast agent-free method to assess these changes
      would be desirable. We assessed changes in cerebral perfusion during MA using
      arterial spin labeling (ASL) perfusion magnetic resonance imaging. METHODS: We
      investigated 4 patients with a standardized protocol including ASL perfusion
      imaging during MA (n = 2) or early headache phase (n = 2) and asymptomatic follow
      up. Semiquantitative evaluation was done using a region of interest (ROI) within
      hypoperfused or hyperperfused areas and corresponding ROIs in the contralateral
      hemisphere. Relative ratios of mean perfusion in the corresponding ROIs were
      calculated. DSC imaging was done at initial time points and compared visually
      with ASL findings. RESULTS: In all patients, regional perfusion changes were
      detected in the acute phase. These abnormalities did not respect the boundaries
      of major cerebral vascular territories but overlapped onto adjoining regions.
      During MA, adjacent hypoperfused and hyperperfused areas were found, whereas
      during headache, regional hyperperfusion only was observed. Perfusion
      abnormalities normalized on follow-up. CONCLUSIONS: ASL perfusion imaging is a
      contrast agent-free method suitable for assessment of reversible perfusion
      changes during or immediately after MA.

PMID- 29331613
TI  - Internal Carotid Artery Web as the Cause of Recurrent Cryptogenic Ischemic
      Stroke.
AB  - Carotid artery web is considered an exceptional cause of recurrent ischemic
      strokes in the affected arterial territory. The underlying pathology proposed for
      this entity is an atypical fibromuscular dysplasia. We present the case of a 43
      year-old woman with no cardiovascular risk factors who had experienced 2
      cryptogenic ischemic strokes in the same arterial territory within an 11-month
      period. Although all diagnostic tests initially yielded normal results, detailed
      analysis of the computed tomography angiography images revealed a carotid web;
      catheter angiography subsequently confirmed the diagnosis. Carotid surgery was
      performed, since which time the patient has remained completely asymptomatic. The
      histological finding of intimal hyperplasia is consistent with previously
      reported cases of carotid artery web. Carotid artery web is an infrequent cause
      of stroke, and this diagnosis requires a high level of suspicion plus a detailed
      analysis of vascular imaging studies.

PMID- 29331614
TI  - The Burden of Stroke Mimics: Present and Future Projections.
AB  - BACKGROUND AND PURPOSE: An increasing proportion of patients presenting with
      suspected stroke prove to have other conditions, often referred to as stroke
      mimics. The aim of this study was to present a projection of the number of
      hospitalized strokes, transient ischemic attacks (TIAs), and stroke mimics in
      Norway up to the year 2050 based on expected demographic changes, to estimate the
      burden of stroke mimics in the coming decades. MATERIALS AND METHODS: This
      prospective study included all admissions to the stroke unit of Akershus
      University Hospital from March 1, 2012, to February 28, 2013. Relevant resource
      use was recorded. Based on the age- and sex-specific absolute incidences for the
      study period, the expected numbers of strokes, TIAs, and stroke mimics in the
      entire Norwegian population were computed for every fifth year for the period
      2020-2050. RESULTS: We included 1881 admissions, of which 38.2% were stroke
      mimics. With constant age- and sex-dependent incidence rates, we estimated that
      the number of strokes and stroke mimics will respectively increase by 121.3% and
      88.7% (men) and 97.6% and 71.7% (women). For hospital admission levels to stay
      constant at the 2013 level, an annual reduction of 2.1% and 1.7% (men) and 1.8%
      and 1.5% (women) must take place for strokes and mimics, respectively.
      CONCLUSIONS: A significant proportion of stroke unit admissions prove to have
      other conditions than stroke. With constant age- and sex-dependent incidence
      rates, the number of stroke mimics admissions will increase substantially over
      the next decades.

PMID- 29331615
TI  - Increased brain glucocorticoid actions following social defeat in rats
      facilitates the long-term establishment of social subordination.
AB  - Social rank is frequently established through aggressive encounters between new
      conspecifics. Despite increasing evidence suggesting that social rank is critical
      for the well-being of both humans and animals, knowledge about the factors
      influencing social rank remain scarce. Stress was previously shown to affect the
      establishment and maintenance of social hierarchies in rats. Likewise, increasing
      systemic corticosterone levels post-encounter in the emerging subordinate rat
      facilitates the long-term establishment of social subordination. Here, we
      investigated whether central corticosterone actions are sufficient to mediate
      this effect. Our data shows that, indeed, an intracerebroventricular
      corticosterone injection given to the emerging subordinate rat facilitates the
      long-term maintenance of the subordinate rank. Next, we attempted to identify a
      particular brain region in which enhancement of corticosterone actions could be
      sufficient to exert the facilitation of a long-term maintenance in the emerging
      subordinate brain. However, post-encounter administration of corticosterone into
      the basolateral amygdala, medial amygdala, lateral septum and the nucleus
      accumbens, brain regions selected for their implication in social rank
      establishment and emotional modulation of memory, did not affect long-term social
      subordination. Our study highlights the involvement of intracerebral
      corticosterone actions on the facilitation of long-lasting subordinate behavior,
      likely by having a modulatory role in the neurobehavioral plasticity engaged in
      the shaping of social subordination.

PMID- 29331616
TI  - Paediatric video laryngoscopy and airway management: What's the clinical
      evidence?
AB  - The major complications of paediatric airway management are uncommon, but the
      outcomes are often severe. Over the last decade, additions and advancements in
      the devices and technology have significantly improved our ability to manage
      difficult paediatric airways safely. Videolaryngoscopy involves the use of video
      and optical technology to facilitate indirect visualisation of the larynx during
      intubation and has been seen as an evolutionary step in intubation technology.
      Over the past few years, videolaryngoscopes have been receiving plenty of
      attention as new airway devices for use in paediatric patients. The objective of
      this narrative review is to specify the existing clinical evidence regarding the
      efficiency and safety of videolaryngoscopy in paediatric airway management.

PMID- 29331617
TI  - Asthma predictive index in relation to respiratory mechanics by impulse
      oscillometry in recurrent wheezers.
AB  - BACKGROUND: The identification of children who will have persistent asthma has
      become a focus of recent research. The aim of this study was to assess whether
      impulse oscillometry (IOS) has a diagnostic value to predict modified API (asthma
      predictive index) in pre-schoolers with recurrent wheezing. METHODS: Pre-school
      children aged 3-6 years with recurrent wheezing were enrolled. The study
      population was divided into two groups based on mAPI criteria. Lung function was
      assessed by IOS. RESULTS: 115 children were assessed; 75 (65.2%) of them were
      male. The median age was 39 months (min: 36, max: 68 months). 64 (55.6%) of the
      children were mAPI positive. The R5-R20% levels of children with positive mAPI
      were significantly higher compared to negative mAPI. Also, R5-R20% levels of
      children with parental asthma and R20% pred and resonant frequency (Fres) levels
      of children with inhalant sensitization were higher than those without. No
      significant differences were found in IOS indices between groups based on the
      presence of atopic dermatitis, food sensitization, eosinophilia, inhaled
      corticosteroid usage or wheezing without colds. R5-R20% and total IgE values were
      found to be significantly related to positive mAPI (aOR: 1.40, p=0.022 and aOR:
      1.02, p=0.001, respectively). In the ROC analysis, R5-R20% levels >14.4 had a
      sensitivity of 75% and specificity of 53% for predicting a positive mAPI
      (p=0.003). CONCLUSION: IOS may help clinicians to identify the pre-school
      wheezers with a high risk of asthma.

PMID- 29331618
TI  - Efficacy and safety of sublingual immunotherapy with Dermatophagoides farinae
      drops in pre-school and school-age children with allergic rhinitis.
AB  - BACKGROUND: The safety and efficacy of sublingual immunotherapy (SLIT) have been
      confirmed by many studies. However, in China, the research on efficacy and safety
      in young and older children with allergic rhinitis (AR) is still rare. OBJECTIVE:
      The aim of this retrospective study is to evaluate the efficacy and safety of
      SLIT with Dermatophagoides farinae drops in pre-school and school-age children
      with AR. METHODS: A total of 282 subjects aged 2-13 years with AR received a two
      year course of sublingual immunotherapy along with pharmacotherapy. According to
      the age, patients were defined as the pre-school group (2-6 years old, n=116) and
      school-age group (7-13 years old, n=166). Total nasal rhinitis symptom scores
      (TNSS), visual analogue score (VAS) and total medication scores (TMS) were
      evaluated at four time points: baseline, after SLIT for half a year, one year and
      two years. The adverse events (AEs) were evaluated at each visit. RESULTS: After
      two-year SLIT, the four rhinitis symptom scores, TNSS, VAS and TMS scores were
      significantly lower than baseline (all P<0.05). The comparison of efficacy
      between one and two-year duration showed no significant difference in global
      clinical outcomes (all P>0.05). In addition, there were no significant
      differences between the pre-school and school-age group in TNSS (all P>0.05), VAS
      (all P>0.05) and TMS scores (P>0.05) after SLIT for half a year, one year and two
      years. No severe systemic AEs were reported. CONCLUSION: SLIT with D. farinae
      drops is clinically effective and safe in pre-school and school-age patients with
      house dust mites (HDMs)-induced AR.

PMID- 29331619
TI  - Mycoplasma pneumoniae and toll-like receptors: A mutual avenue.
AB  - Mycoplasma pneumoniae is an intracellular bacterium leading to several
      complications in humans. M. pneumoniae is cleared in some cases and induces
      complications in others. The main responsible mechanisms regarding the
      controversy are yet to be cleared. Toll-like receptors (TLRs) are the important
      cell membrane and intracellular receptors which recognize a wide range of
      microbial macromolecules. The roles of TLRs in the eradication of several
      pathogens and also induction of their related complications have been
      demonstrated. This review article presents recent data about the roles of TLRs in
      the induction of immune responses which lead to M. pneumoniae eradication and
      related complications.

PMID- 29331620
TI  - Antagonistic effect of nano-ZnO and cetyltrimethyl ammonium chloride on the
      growth of Chlorella vulgaris: Dissolution and accumulation of nano-ZnO.
AB  - The interaction of nanoparticles with coexisting chemicals affects the fate and
      transport of nanoparticles, as well as their combined effects on aquatic
      organisms. Here, we evaluated the joint effect of ZnO nanoparticle (nano-ZnO) and
      cetyltrimethyl ammonium chloride (CTAC) on the growth of Chlorella vulgaris and
      explored the possible mechanism. Results showed that an antagonistic effect of
      nano-ZnO and CTAC (0.1, 0.2 and 0.3 mg L-1) was found because CTAC stop nano-ZnO
      being broken down into solution zinc ions (Zn2+). In the presence of CTAC, the
      zinc (including nano-ZnO and released Zn2+) showed a higher adsorption on bound
      extracellular polymeric substances (B-EPS) but lower accumulation in the algal
      cells. Moreover, we directly demonstrated that nano-ZnO was adsorbed on the algal
      B-EPS and entered into the algal cells by transmission electron microscope
      coupled with energy dispersive X-ray (TEM-EDX). Hence, these results suggested
      that the combined system of nano-ZnO and CTAC exhibited an antagonistic effect
      due to the inhibition of CTAC on dissolution of nano-ZnO and accumulation of the
      zinc in the algal cells.

PMID- 29331621
TI  - Silver ion-enhanced particle-specific cytotoxicity of silver nanoparticles and
      effect on the production of extracellular secretions of Phanerochaete
      chrysosporium.
AB  - This study investigated the influence of silver ions (Ag+) on the cytotoxicity of
      silver nanoparticles (AgNPs) in Phanerochaete chrysosporium and noted the degree
      of extracellular secretions in response to the toxicant's stress. Oxalate
      production was elicited with moderate concentrations of 2,4-dichlorophenol (2,4
      DCP) and AgNPs reaching a plateau at 10 mg/L and 10 MUM, respectively. Increased
      oxalate accumulation was accompanied by higher activities of manganese peroxidase
      (MnP) and lignin peroxidase (LiP). However, the secretion of oxalate, MnP and LiP
      was significantly inhibited owing to Ag+ incorporation into AgNP solution.
      Production of extracellular polymeric substances (EPS) significantly elevated
      with an increase in 2,4-DCP concentrations; however, after 24 h of exposure to
      100 mg/L 2,4-DCP, an obvious decrease in EPS occurred, indicating that part of
      EPS could be consumed as carbon and energy sources to ameliorate biological
      tolerance to toxic stress. Furthermore, AgNP-induced "particle-specific"
      cytotoxicity was substantially enhanced with additional Ag+ as evidenced by its
      significant negative impact on cellular growth, plasma membrane integrity, and
      morphological preservation compared with AgNPs at equal Ag concentration.

PMID- 29331622
TI  - Value of Serial Multiparametric Magnetic Resonance Imaging and Magnetic Resonance
      Imaging-guided Biopsies in Men with Low-risk Prostate Cancer on Active
      Surveillance After 1 Yr Follow-up.
AB  - BACKGROUND: Active surveillance (AS) aims to reduce overtreatment of low-risk
      prostate cancer (PC). Incorporating multiparametric magnetic resonance imaging
      (mp-MRI) and MR-guided biopsy (MRGB) in an AS protocol might contribute to more
      accurate identification of AS candidates. OBJECTIVE: To evaluate the value of 3T
      mp-MRI and MRGB in PC patients on AS at inclusion and after 12-mo follow-up.
      DESIGN, SETTING, AND PARTICIPANTS: Patients with cT1c-cT2 PC, prostate-specific
      antigen (PSA) <=10ng/ml, PSA density <0.2ng/ml/ml, and Gleason scores (GSs) of
      <=6 and <=2 positive biopsy cores were included and followed in an AS protocol
      including mp-MRI and MRGB. The mp-MRI and MRGB were performed at <3 and 12 mo
      after diagnosis. Reclassification was defined as GS >6, >2 positive cores at
      repeat transrectal ultrasound-guided biopsy (TRUSGB), presence of PC in >3
      separate cancer foci upon both MRGB and TRUSGB, or cT3 tumor on mp-MRI. OUTCOME
      MEASUREMENTS AND STATISTICAL ANALYSIS: Reclassification rates, treatment after
      discontinuation, and outcome on radical prostatectomy after discontinuing AS were
      reported. Uni- and multivariate analyses were performed to identify predictors of
      reclassification after 1 yr. RESULTS AND LIMITATIONS: From 2009 to 2013, a total
      of 111 of 158 patients were consecutively and prospectively included. Around
      initial diagnosis, 36 patients were excluded from the study protocol; mp-MRI+MRGB
      reclassified 25/111 (23%) patients, and 11 patients were excluded at own request.
      Reasons for reclassification were as follows: GS upgrade (15/25, 60%); cT3
      disease (3/25, 12%); suspicion of bone metastases (1/25, 4%); and multifocal
      disease upon MRGB (6/25, 24%). Repeat examinations after 1 yr showed
      reclassification in 33/75 patients (44%). Reasons were the following: GS upgrade
      upon TRUSGB (9/33, 27%); volume progression upon TRUSGB (9/33, 27%); cT3 disease
      upon mp-MRI (1/33, 3%); GS upgrade upon MRGB (1/33, 3%); volume progression upon
      MRGB (1/33, 3%); multifocal disease upon MRGB (2/33, 6%); and upgrade or upstage
      upon both TRUSGB and MRGB (10/33, 30%). On logistic regression analysis, the
      presence of cancer at initial mp-MRI and MRGB examinations was the only predictor
      of reclassification after 1 yr (odds ratio 5.9, 95% confidence interval 2.0
      17.6). CONCLUSIONS: Although mp-MRI and MRGB are of additional value in the
      evaluation of PC patients on AS, the value of mp-MRI after 1 yr was limited. As a
      considerable percentage of GS >=7 PC after 1 yr was detected only by TRUSGB,
      TRUSGB cannot be omitted yet. PATIENT SUMMARY: More aggressive tumors are
      detected if low-risk prostate cancer patients are additionally monitored by
      magnetic resonance imaging. However, some high-grade tumors are detected only by
      transrectal ultrasound-guided biopsy.

PMID- 29331623
TI  - Male Sexual Dysfunction and Hypogonadism Guidelines for the Aging Male.
AB  - Cognitive and somatiform changes occur with ageing and are often attributed to
      late-onset hypogonadism. Testosterone replacement in older men remains
      controversial despite increasing evidence of symptomatic and clinical benefit in
      relation to improvements in sexual dysfunction, muscle mass, and diabetic
      control. The controversial areas related to cardiovascular safety and risk of
      prostate cancer need to be considered.

PMID- 29331624
TI  - Comprehensive Geriatric Assessment in the Older Adult with Cancer: A Review.
AB  - CONTEXT: The number of older adults with cancer is expected to increase rapidly
      in the upcoming decades. Aging is heterogeneous and chronological age is often
      not reflective of biological age. A comprehensive geriatric assessment (CGA) is
      an in-depth assessment of multiple domains of health that results in better
      assessment of a patient's overall health and fitness and allows directed
      intervention to improve patient outcomes. OBJECTIVE: To review the value of CGA
      for older adults with cancer, CGA composition and tools that can be utilized, and
      the feasibility of including CGA in oncologic practice. EVIDENCE ACQUISITION: The
      currently available evidence on CGA for older adults with cancer was reviewed.
      EVIDENCE SYNTHESIS: A CGA can highlight unidentified health problems and identify
      patients at higher risk of mortality, functional decline, surgical complications,
      chemotherapy intolerance, and chemotherapy toxicity. It has been shown that CGA
      is feasible in the oncology clinic, but geriatric screening tools may be useful
      to specifically identify patients who would benefit from a full CGA. CONCLUSIONS:
      CGA is feasible and can identify patients at higher risk of adverse events such
      as mortality, functional decline, surgical complications, and chemotherapy
      toxicity. Clinicians should consider incorporating CGA when assessing and caring
      for older adults with cancer. PATIENT SUMMARY: In this report, we review the
      benefits of a comprehensive geriatric assessment (CGA), a detailed in-depth
      assessment that identifies health problems not typically identified during
      routine assessments, for older adults with cancer. We describe the different
      domains of the CGA and suggest tools to utilize, as well as ways to incorporate
      CGA into the cancer care setting.

PMID- 29331625
TI  - Proposing priorities of intervention for the recovery of native fish populations
      using hierarchical ranking of environmental and exotic species impact.
AB  - The freshwater populations of native fish species (Ns) have reached critical
      levels in many parts of the world due to combined habitat deterioration by human
      interventions and exotic fish species (Es) invasions. These alarming conditions
      require combined and well-designed interventions for restoring environmental
      quality and restricting Es invasion. The aim of the study is to propose a method
      to design spatially explicit priorities of intervention for the recovery of Ns
      populations in highly impacted freshwater systems by exotic multi-species
      invasion and water quality (WQ) degradation. WQ and Es are used as Ns
      descriptors, which require intervention. The method uses gradient analysis
      (ordination method of Canonical Correspondence Analysis) for assessing the
      weights of Ns descriptors' effects, which are further used to develop weighted
      severity indices; the severity index of WQ (Swq) and Es invasion (Se),
      respectively. Swq and Se are further merged to one combined total severity index
      St. The proposed method provides a) a ranking of the sites, based on the values
      of St, which denotes the priority for combined intervention in space and can be
      visualized in maps, b) a ranking of the most important Ns descriptors for each
      site to perform site-specific interventions, and c) Es rankings based on their
      potential threat on Ns for species-specific interventions. WQ, Es and Ns data
      from 208 sampling sites located in the Emilia-Romagna Region (Northern Italy)
      were used as a case study for the presentation of the proposed method. The
      application of the method showed that the north and northwestern lowland areas of
      Emilia-Romagna region presented the higher priority for intervention since the Ns
      of these areas are the most impacted from combined Es invasions and WQ
      degradation. Specific Es belonging to cyprinids, which are mostly responsible for
      the decline of aquatic vegetation and the increase of water turbidity, and a top
      Es predator (Wels catfish) were mostly present in these areas. Additionally, the
      most important WQ stressors of Ns were found to be COD, BOD and temperature that
      are all connected to oxygen depletion. The aforementioned conditions in the areas
      described by high priority for intervention can be used as a basis for the
      development of specific Ns conservation practices targeting the containment of
      the most harmful Es, the restoration of aquatic vegetation and the improvement of
      oxygen conditions.

PMID- 29331626
TI  - Implicit individual discount rate in China: A contingent valuation study.
AB  - Two contingent valuation (CV) surveys were conducted in Kunming, China, to
      estimate households' willingness to pay (WTP) for the Panlong River
      rehabilitation project. The two surveys were conducted using the same procedures
      and questionnaires except for the payment schedule arrangements, which permitted
      a calculation of respondents' implicit discount rate. The surveys provided two
      estimates of WTP, one with a mean of 23 Yuan in monthly payment over 5 years and
      the other with a mean of 311 Yuan in a lump-sum payment that will cover all the
      expenses for a period of 5 years. The results produce an estimate of monthly
      discount rate of 7.6%-12.6% or annual discount rate of 141-315%. The estimates
      are higher than that reported from those studies conducted in the U.S., but are
      compatible with that of some other studies. This study also shows that both mean
      individual WTP and implicit individual discount rates are closely related to
      household demographic and economic characteristics and environment-related
      perceptions, as reported in the studies conducted in other countries.

PMID- 29331627
TI  - Use of interactive data visualization in multi-objective forest planning.
AB  - Common to multi-objective forest planning situations is that they all require
      comparisons, searches and evaluation among decision alternatives. Through these
      actions, the decision maker can learn from the information presented and thus
      make well-justified decisions. Interactive data visualization is an evolving
      approach that supports learning and decision making in multidimensional decision
      problems and planning processes. Data visualization contributes the formation of
      mental image data and this process is further boosted by allowing interaction
      with the data. In this study, we introduce a multi-objective forest planning
      decision problem framework and the corresponding characteristics of data. We
      utilize the framework with example planning data to illustrate and evaluate the
      potential of 14 interactive data visualization techniques to support multi
      objective forest planning decisions. Furthermore, broader utilization
      possibilities of these techniques to incorporate the provisioning of ecosystem
      services into forest management and planning are discussed.

PMID- 29331628
TI  - Getting into the Swing of things: An investigation into rhythmic unimanual
      coordination in typically developing children.
AB  - Unimanual coordination is a vital component of everyday life and underpins
      successful engagement of many activities of daily living and physical activity
      participation. The ability to coordinate with environmental stimuli has been
      extensively studied in adults in a variety of situations. However, we know little
      about these processes in children and even less about how these processes change
      as age increases. This paper examines children's performance in a rhythmic
      unimanual coordination task using a handheld pendulum. Participants (aged 6, 9
      and 11 years) manipulated the pendulum at 3 frequencies (preferred frequency,
      +20% of preferred and -20% of preferred frequency) in coordination with 3 stimuli
      (Visual, Auditory and Visual-Auditory combined). Results showed that children's
      coordination levels and movement variability improved with age, however still
      fell below those observed in adults. In addition children demonstrated
      preferences for visual stimuli or multisensory stimuli compared to auditory
      stimuli on their own Interestingly, children were found to demonstrate different
      movement amplitudes for -20%, preferred and +20% frequency conditions. In
      conclusion, children's unimanual coordination levels were found to follow the
      typical maturation process and improve with age. Further to this, findings
      suggest the potential benefit of multisensory information for uni manual
      coordination in children.

PMID- 29331629
TI  - Growth and maturity: A quantitative systematic review and network analysis in
      anthropometric history.
AB  - This paper reviews the current wealth of anthropometric history since the early
      efforts of Robert Fogel in the 1970s. The survey is based on a quantitative
      systematic review of the literature and counts a total of 447 peer-reviewed
      articles being published in the main leading journals in economic history,
      economics and biology. Data are analysed using network analysis by journal and
      author and the main contributions of anthropometric history are highlighted,
      pointing to future areas of inquiry. The contributions of books and book chapters
      are also quantified and analysed.

PMID- 29331630
TI  - mRNA function after intracellular delivery and release.
AB  - Nanocarrier-mediated mRNA delivery and release into the cells with subsequent
      translation to protein is of interest in the context of the development of a new
      generation of drugs. In particular, this protein can play a role of a
      transcription factor and be used as a tool to regulate temporarily the genetic
      networks. The corresponding transient kinetics of gene expression are expected to
      depend on the mechanism and duration of mRNA release. Assuming the release to be
      rapid on the time scale of other steps, the author shows theoretically the mRNA
      related transient features of gene expression occurring in stable, bistable, and
      oscillatory regimes in a single cell. Qualitatively, the results obtained are
      found to be fairly similar to those reported earlier for the situation when the
      release is slow. Thus, the features of the transient kinetics under consideration
      appear to be less sensitive to the duration of mRNA release compared to what one
      might expect.

PMID- 29331632
TI  - CT scanning to diagnose CAA: back to the future?

PMID- 29331631
TI  - The Edinburgh CT and genetic diagnostic criteria for lobar intracerebral
      haemorrhage associated with cerebral amyloid angiopathy: model development and
      diagnostic test accuracy study.
AB  - BACKGROUND: Identification of lobar spontaneous intracerebral haemorrhage
      associated with cerebral amyloid angiopathy (CAA) is important because it is
      associated with a higher risk of recurrent intracerebral haemorrhage than
      arteriolosclerosis-associated intracerebral haemorrhage. We aimed to develop a
      prediction model for the identification of CAA-associated lobar intracerebral
      haemorrhage using CT features and genotype. METHODS: We identified adults with
      first-ever intracerebral haemorrhage diagnosed by CT, who died and underwent
      research autopsy as part of the Lothian IntraCerebral Haemorrhage, Pathology,
      Imaging and Neurological Outcome (LINCHPIN) study, a prospective, population
      based, inception cohort. We determined APOE genotype and radiologists rated CT
      imaging appearances. Radiologists were not aware of clinical, genetic, and
      histopathological features. A neuropathologist rated brain tissue for small
      vessel diseases, including CAA, and was masked to clinical, radiographic, and
      genetic features. We used CT and APOE genotype data in a logistic regression
      model, which we internally validated using bootstrapping, to predict the risk of
      CAA-associated lobar intracerebral haemorrhage, derive diagnostic criteria, and
      estimate diagnostic accuracy. FINDINGS: Among 110 adults (median age 83 years
      [IQR 76-87], 49 [45%] men) included in the LINCHPIN study between June 1, 2010
      and Feb 10, 2016, intracerebral haemorrhage was lobar in 62 (56%) participants,
      deep in 41 (37%), and infratentorial in seven (6%). Of the 62 participants with
      lobar intracerebral haemorrhage, 36 (58%) were associated with moderate or severe
      CAA compared with 26 (42%) that were associated with absent or mild CAA, and were
      independently associated with subarachnoid haemorrhage (32 [89%] of 36 vs 11
      [42%] of 26; p=0.014), intracerebral haemorrhage with finger-like projections (14
      [39%] of 36 vs 0; p=0.043), and APOE E4 possession (18 [50%] of 36 vs 2 [8%] of
      26; p=0.0020). A prediction model for CAA-associated lobar intracerebral
      haemorrhage using these three variables had excellent discrimination (c statistic
      0.92, 95% CI 0.86-0.98), confirmed by internal validation. For the rule-out
      criteria, neither subarachnoid haemorrhage nor APOE E4 possession had 100%
      sensitivity (95% CI 88-100). For the rule-in criteria, subarachnoid haemorrhage
      and either APOE E4 possession or finger-like projections had 96% specificity (95%
      CI 78-100). INTERPRETATION: The CT and APOE genotype prediction model for CAA
      associated lobar intracerebral haemorrhage shows excellent discrimination in this
      cohort, but requires external validation. The Edinburgh rule-in and rule-out
      diagnostic criteria might inform prognostic and therapeutic decisions that depend
      on identification of CAA-associated lobar intracerebral haemorrhage. FUNDING: UK
      Medical Research Council, The Stroke Association, and The Wellcome Trust.

PMID- 29331633
TI  - Organ donation in the ICU: A document analysis of institutional policies,
      protocols, and order sets.
AB  - OBJECTIVE: To better understand how local policies influence organ donation
      rates. RESEARCH METHODOLOGY/DESIGN: We conducted a document analysis of our ICU
      organ donation policies, protocols and order sets. We used a systematic search of
      our institution's policy library to identify documents related to organ donation.
      We used Mindnode software to create a publication timeline, basic statistics to
      describe document characteristics, and qualitative content analysis to extract
      document themes. SETTING: Documents were retrieved from Hamilton Health Sciences,
      an academic hospital system with a high volume of organ donation, from database
      inception to October 2015. FINDINGS: We retrieved 12 active organ donation
      documents, including six protocols, two policies, two order sets, and two
      unclassified documents, a majority (75%) after the introduction of donation after
      circulatory death in 2006. Four major themes emerged: organ donation process,
      quality of care, patient and family-centred care, and the role of the
      institution. These themes indicate areas where documented institutional standards
      may be beneficial. CONCLUSION: Further research is necessary to determine the
      relationship of local policies, protocols, and order sets to actual organ
      donation practices, and to identify barriers and facilitators to improving
      donation rates.

PMID- 29331634
TI  - Of blood and bone: the sotatercept adventure.

PMID- 29331636
TI  - Cell wall damage and oxidative stress in Candida albicans ATCC10231 and
      Aspergillus niger caused by palladium nanoparticles.
AB  - In this work the toxic effect of Palladium nanoparticles (PdNPs) was investigated
      in two eukaryotic cell models, Candida albicans and Aspergillus niger. PdNPs were
      synthesized by chemical reduction method, obtaining spherical NPs with a primary
      size ranging from 3 to 15 nm. PdNPs showed a hydrodynamic size of 1548 nm in
      Lee's minimum media. Minimal inhibitory concentration was determined at 200 and
      250 ppm for Candida albicans and Aspergillus niger respectively, revealing a
      significant cell growth inhibition (ANOVA and tukey analysis, alpha = 0.5).
      Reactive Oxygen Species levels were increased in both microorganisms. Confocal,
      scanning and transmission electron microscopy studies revealed cell wall damage
      and cellular morphology changes, induced by the interaction of PdNPs, in both
      microorganisms.

PMID- 29331635
TI  - Sotatercept with long-term extension for the treatment of anaemia in patients
      with lower-risk myelodysplastic syndromes: a phase 2, dose-ranging trial.
AB  - BACKGROUND: Myelodysplastic syndromes are characterised by ineffective
      erythropoiesis leading to anaemia. Sotatercept (ACE-011) is a novel activin
      receptor type IIA fusion protein that acts as a ligand trap to neutralise
      negative regulators of late-stage erythropoiesis. The aim of the study was to
      establish a safe and effective dose of sotatercept for the treatment of anaemia
      in patients with lower-risk myelodysplastic syndromes. METHODS: This open-label,
      multicentre, dose-ranging, phase 2 trial took place at 11 treatment centres in
      the USA and France. Eligible patients were aged 18 years or older, had
      International Prognostic Scoring System-defined low-risk or intermediate-1-risk
      myelodysplastic syndromes, had anaemia requiring red blood cell (RBC)
      transfusions, and were ineligible for, or refractory to, erythropoiesis
      stimulating agents (ESAs). Patients were not eligible if they had chromosome 5q
      deletion myelodysplastic syndromes without documented failure of lenalidomide.
      Patients were randomly assigned to receive either 0.1 or 0.3 mg/kg sotatercept
      subcutaneously, using a permuted-block method with stratification for serum
      erythropoietin concentration and transfusion burden. Patients were assigned to
      0.5, 1.0, and 2.0 mg/kg groups in a non-randomised fashion. The primary efficacy
      endpoint was the proportion of patients who achieved haematological improvement
      erythroid (HI-E), according to International Working Group 2006 criteria.
      Efficacy and safety analyses were done in the intention-to-treat population. This
      trial is registered at ClinicalTrials.gov, number NCT01736683 and at EU Clinical
      Trials Register, number 2012-002601-22, and is ongoing. FINDINGS: Between Dec 5,
      2012, and July 22, 2015, 74 patients were enrolled into the study (seven to
      receive 0.1 mg/kg sotatercept, six to 0.3 mg/kg, 21 to 0.5 mg/kg, 35 to 1.0
      mg/kg, and five to 2.0 mg/kg). 36 (49%; 95% CI 38-60) of 74 patients achieved HI
      E; 29 (47%; 95% CI 35-59) of 62 patients with a high transfusion burden achieved
      HI-E (RBC-transfusion reduction from baseline of 4 or more units for at least 56
      days), and seven (58%; 95% CI 32-81) of 12 patients with a low transfusion burden
      achieved HI-E (haemoglobin increase of 1.5 g/dL or more sustained for at least 56
      days in the absence of transfusions). The most commonly reported adverse events
      were fatigue in 19 (26%) of 74 patients and peripheral oedema in 18 (24%) of 74
      patients. Grade 3-4 treatment-emergent adverse events (TEAEs) were reported in 25
      (34%) of 74 patients; four (5%) patients had grade 3-4 TEAEs that were considered
      to be treatment related. The most common grade 3-4 TEAEs were lipase increase and
      anaemia, which each occurred in three (4%) of 74 patients. 17 (23%) of 74
      patients had at least one serious TEAE, and one patient died from a treatment
      emergent subdural haematoma due to a fall. INTERPRETATION: Sotatercept, a novel
      activin-receptor fusion protein, was well tolerated and effective for the
      treatment of anaemia in patients with lower-risk myelodysplastic syndromes in
      whom previous ESA treatment had failed. Treatment with sotatercept could be
      beneficial for these patients who have few available treatment options. FUNDING:
      Celgene Corporation.

PMID- 29331637
TI  - Development of a multi-dimensional scale to measure trauma associated with child
      sexual abuse (MSCSA) and its ramifying impacts on children: A pilot study.
AB  - BACKGROUND: With the rising incidence of CSA in India and absence of culturally
      competent tool to assess the impact of trauma, there is a dire need for
      development of a comprehensive scale to assess the impact of trauma on children.
      Thus, the present study aims to develop a multi-dimensional CSA tool for children
      aged between 7 and 13 years. METHOD: Qualitative research method of FGD/Key
      Interviews with 4 group participants (Parents, counsellors, mental health and
      medical professionals) and in-depth interview with children having history of CSA
      was conducted along with item pooling from existing scales. Scale domain and sub
      constructs were identified through thematic analysis of the qualitative data and
      statements extracted through item pooling. Face and content validity was obtained
      followed by the administration of the scale on pilot sample of 30 children
      meeting selection criteria of the study. RESULTS: 6 domains of the multi
      dimensional impact of trauma was identified (i.e. Behavioral, Emotional,
      Cognition, Biological, Psychopathology and Social Functioning) which was
      constructed in the form of 85 scale statements across 6 domains and 48 sub
      constructs on a 3-point Likert scale of response in both Hindi as well as English
      language. The scale was found to be having high reliability and average inter
      item and inter-domain correlation. Modification of scale items based on pilot
      study findings and expert feedback analysis done to obtain a final scale
      containing 78 items. DISCUSSION: Discussion done primarily in terms of scale's
      psychometric properties, its clinical & research implications, especially
      focusing on cultural competency of the scale.

PMID- 29331638
TI  - Comparative analysis of membrane protein structure databases.
AB  - BACKGROUND: Membrane proteins play important roles in cell survival and cell
      communication, as they function as transporters, receptors, anchors and enzymes.
      They are also potential targets for drugs that block receptors or inhibit enzymes
      related to diseases. Although the number of known structures of membrane proteins
      is still small relative to the size of the proteome as a whole, many new membrane
      protein structures have been determined recently. SCOPE OF THE ARTICLE: We
      compared and analyzed the widely used membrane protein databases, mpstruc,
      Orientations of Proteins in Membranes (OPM), and PDBTM, as well as the extended
      dataset of mpstruc based on sequence similarity, the PDB structures whose
      classification field indicates that they are "membrane proteins" and the proteins
      with Structural Classification of Proteins (SCOP) class-f domains. We evaluated
      the relationships between these databases or datasets based on the overlap in
      their contents and the degree of consistency in the structural, topological, and
      functional classifications and in the transmembrane domain assignment. MAJOR
      CONCLUSIONS: The membrane databases differ from each other in their coverage, and
      in the criteria that they use for annotation and classification. To ensure the
      efficient use of these databases, it is important to understand their differences
      and similarities. The establishment of more detailed and consistent annotations
      for the sequence, structure, membrane association, and function of membrane
      proteins is still required. GENERAL SIGNIFICANCE: Considering the recent growth
      of experimentally determined structures, a broad survey and cumulative analysis
      of the sum of knowledge as presented in the membrane protein structure databases
      can be helpful to elucidate structures and functions of membrane proteins. We
      also aim to provide a framework for future research and classification of
      membrane proteins.

PMID- 29331639
TI  - Identification of the disinfection byproducts of bisphenol S and the disrupting
      effect on peroxisome proliferator-activated receptor gamma (PPARgamma) induced by
      chlorination.
AB  - Bisphenol S (BPS), an alternative product to bisphenol A (BPA), has been the
      focus of increasing public concern due to its potential endocrine disrupting
      effect and its adverse effects related to metabolic disorders such as obesity.
      The detection of its residue in drinking water supply systems suggests that BPS
      can be chlorinated; however, whether its endocrine disrupting effect can be
      disrupted by this chlorination remains unclear. In the present study, we
      identified the byproducts of the reaction of BPS with chlorine and assessed the
      effect of the main byproducts on peroxisome proliferator-activated receptor gamma
      (PPARgamma). BPS was chlorinated in a simulation experiment. The chlorination
      reaction in this study was chlorine and pH dependent, and the pseudo-first-order
      reaction rate constant was controlled by the chlorine concentration and pH. The
      reaction rate at pH 8.5 was 7 times faster than that at pH 6.5. Twenty-two
      byproducts were putatively identified by liquid chromatography quadrupole time-of
      flight mass spectrometry (LC-ESI-Q-ToF-MS), and five main byproducts were
      purified and characterized by 1H and 13C nuclear magnetic resonance (NMR)
      spectroscopy. The PPARgamma effects of the byproducts were assayed, revealing a2
      to4-fold enhancement in their activities in comparison with the parent compound.

PMID- 29331640
TI  - Recent advances in application of UV light-emitting diodes for degrading organic
      pollutants in water through advanced oxidation processes: A review.
AB  - Over the last decade, ultraviolet light-emitting diodes (UV LEDs) have attracted
      considerable attention as alternative mercury-free UV sources for water treatment
      purposes. This review is a comprehensive analysis of data reported in recent
      years (mostly, post 2014) on the application of UV LED-induced advanced oxidation
      processes (AOPs) to degrade organic pollutants, primarily dyes, phenols,
      pharmaceuticals, insecticides, estrogens and cyanotoxins, in aqueous media.
      Heterogeneous TiO2-based photocatalysis in lab grade water using UVA LEDs is the
      most frequently applied method for treating organic contaminants. The effects of
      controlled periodic illumination, different TiO2-based nanostructures and reactor
      types on degradation kinetics and mineralization are discussed. UVB and UVC LEDs
      have been used for photo-Fenton, photo-Fenton-like and UV/H2O2 treatment of
      pollutants, primarily, in model aqueous solutions. Notably, UV LED-activated
      persulfate/peroxymonosulfate processes were capable of providing degradation in
      DOC-containing waters. Wall-plug efficiency, energy-efficiency of UV LEDs and the
      energy requirements in terms of Electrical Energy per Order (EEO) are discussed
      and compared. Despite the overall high degradation efficiency of the UV LED-based
      AOPs, practical implementation is still limited and at lab scale. More research
      on real water matrices at more environmentally relevant concentrations, as well
      as an estimation of energy requirements providing fluence-based kinetic data are
      required.

PMID- 29331641
TI  - Enzymes from piezophiles.
AB  - The discovery of microbial communities in extreme conditions that would seem
      hostile to life leads to the question of how the molecules making up these
      microbes can maintain their structure and function. While microbes that live
      under extremes of temperature have been heavily studied, those that live under
      extremes of pressure, or "piezophiles", are now increasingly being studied
      because of advances in sample collection and high-pressure cells for biochemical
      and biophysical measurements. Here, adaptations of enzymes in piezophiles against
      the effects of pressure are discussed in light of recent experimental and
      computational studies. However, while concepts from studies of enzymes from
      temperature extremophiles can provide frameworks for understanding adaptations by
      piezophile enzymes, the effects of temperature and pressure on proteins differ in
      significant ways. Thus, the state of the knowledge of adaptation in piezophile
      enzymes is still in its infancy and many more experiments and computational
      studies on different enzymes from a variety of piezophiles are needed.

PMID- 29331642
TI  - Protein adaptations in extremophiles: An insight into extremophilic connection of
      mycobacterial proteome.
AB  - The biological paradox about how extremophiles persist at extreme ecological
      conditions throws a fascinating picture of the enormous potential of a single
      cell to adapt to homeostatic conditions in order to propagate. Unicellular
      organisms face challenges from both environmental factors and the ecological
      niche provided by the host tissue. Although the existence of extremophiles and
      their physiological properties were known for a long time, availability of whole
      genome sequence has catapulted the study on mechanisms of adaptation and the
      underlying principles that have enabled these unique organisms to withstand
      evolutionary and environmental pressures. Comparative genomics has shown that
      extremophiles possess the unique set of genes and proteins that empower them with
      biochemical machinery necessary to thrive in extreme environments. The presence
      of these proteins safeguards the cell against a wide array of extreme conditions
      such as temperature, pressure, radiations, chemicals, drugs etc. An insight into
      these adaptive mechanisms in extremophiles may help us to devise strategies to
      alter the genes and proteins that may have therapeutic potential and commercial
      value. Here we present an overview of the various adaptations in extremophiles.
      We also try to explain how mycobacterium channelizes its proteome to survive in
      stress conditions posed by host immune system.

PMID- 29331643
TI  - Glucagon-like peptide 1 signaling inhibits allergen-induced lung IL-33 release
      and reduces group 2 innate lymphoid cell cytokine production in vivo.
AB  - BACKGROUND: IL-33 is one of the most consistently associated gene candidates for
      asthma identified by using a genome-wide association study. Studies in mice and
      in human cells have confirmed the importance of IL-33 in inducing type 2 cytokine
      production from both group 2 innate lymphoid cells (ILC2s) and TH2 cells.
      However, there are no pharmacologic agents known to inhibit IL-33 release from
      airway cells. OBJECTIVE: We sought to determine the effect of glucagon-like
      peptide 1 receptor (GLP-1R) signaling on aeroallergen-induced airway IL-33
      production and release and on innate type 2 airway inflammation. METHODS: BALB/c
      mice were challenged intranasally with Alternaria extract for 4 consecutive days.
      GLP-1R agonist or vehicle was administered starting either 2 days before the
      first Alternaria extract challenge or 1 day after the first Alternaria extract
      challenge. RESULTS: GLP-1R agonist treatment starting 2 days before the first
      Alternaria extract challenge decreased IL-33 release in the bronchoalveolar
      lavage fluid and dual oxidase 1 (Duox1) mRNA expression 1 hour after the first
      Alternaria extract challenge and IL-33 expression in lung epithelial cells 24
      hours after the last Alternaria extract challenge. Furthermore, GLP-1R agonist
      significantly decreased the number of ILC2s expressing IL-5 and IL-13, lung
      protein expression of type 2 cytokines and chemokines, the number of perivascular
      eosinophils, mucus production, and airway responsiveness compared with vehicle
      treatment. GLP-1R agonist treatment starting 1 day after the first Alternaria
      extract challenge also significantly decreased eosinophilia and type 2 cytokine
      and chemokine expression in the airway after 4 days of Alternaria extract
      challenge. CONCLUSION: These results reveal that GLP-1R signaling might be a
      therapy to reduce IL-33 release and inhibit the ILC2 response to protease
      containing aeroallergens, such as Alternaria.

PMID- 29331644
TI  - Ozone exposure induces respiratory barrier biphasic injury and inflammation
      controlled by IL-33.
AB  - BACKGROUND: IL-33 plays a critical role in regulation of tissue homeostasis,
      injury, and repair. Whether IL-33 regulates neutrophil recruitment and functions
      independently of airways hyperresponsiveness (AHR) in the setting of ozone
      induced lung injury and inflammation is unclear. OBJECTIVE: We sought to examine
      the role of the IL-33/ST2 axis in lung inflammation on acute ozone exposure in
      mice. METHODS: ST2- and Il33-deficient, IL-33 citrine reporter, and C57BL/6 (wild
      type) mice underwent a single ozone exposure (1 ppm for 1 hour) in all studies.
      Cell recruitment in lung tissue and the bronchoalveolar space, inflammatory
      parameters, epithelial barrier damage, and airway hyperresponsiveness (AHR) were
      determined. RESULTS: We report that a single ozone exposure causes rapid
      disruption of the epithelial barrier within 1 hour, followed by a second phase of
      respiratory barrier injury with increased neutrophil recruitment, reactive oxygen
      species production, AHR, and IL-33 expression in epithelial and myeloid cells in
      wild-type mice. In the absence of IL-33 or IL-33 receptor/ST2, epithelial cell
      injury with protein leak and myeloid cell recruitment and inflammation are
      further increased, whereas the tight junction proteins E-cadherin and zonula
      occludens 1 and reactive oxygen species expression in neutrophils and AHR are
      diminished. ST2 neutralization recapitulated the enhanced ozone-induced
      neutrophilic inflammation. However, myeloid cell depletion using GR-1 antibody
      reduced ozone-induced lung inflammation, epithelial cell injury, and protein
      leak, whereas administration of recombinant mouse IL-33 reduced neutrophil
      recruitment in Il33-deficient mice. CONCLUSION: Data demonstrate that ozone
      causes an immediate barrier injury that precedes myeloid cell-mediated
      inflammatory injury under the control of the IL-33/ST2 axis. Thus IL-33/ST2
      signaling is critical for maintenance of intact epithelial barrier and
      inflammation.

PMID- 29331645
TI  - Realising the potential of various inhaled airway challenge agents through
      improved delivery to the lungs.
AB  - Inhaled airway challenges provoke bronchoconstriction in susceptible subjects and
      are a pivotal tool in the diagnosis and monitoring of obstructive lung diseases,
      both in the clinic and in the development of new respiratory medicines. This
      article reviews the main challenge agents that are in use today (methacholine,
      mannitol, adenosine, allergens, endotoxin) and emphasises the importance of
      controlling how these agents are administered. There is a danger that the optimal
      value of these challenge agents may not be realised due to suboptimal inhaled
      delivery; thus considerations for effective and reproducible challenge delivery
      are provided. This article seeks to increase awareness of the importance of
      precise delivery of inhaled agents used to challenge the airways for diagnosis
      and research, and is intended as a stepping stone towards much-needed
      standardisation and harmonisation in the administration of inhaled airway
      challenge agents.

PMID- 29331646
TI  - Progress in the Management of Advanced Thoracic Malignancies in 2017.
AB  - The treatment paradigm of NSCLC underwent a major revolution during the course of
      2017. Immune checkpoint inhibitors (ICIs) brought remarkable improvements in
      response and overall survival both in unselected pretreated patients and in
      untreated patients with programmed death ligand 1 expression of 50% or more.
      Furthermore, compelling preliminary results were reported for new combinations of
      anti-programmed cell death 1/programmed death ligand 1 agents with chemotherapy
      or anti-cytotoxic T-lymphocyte associated protein 4 inhibitors. The success of
      the ICIs appeared to extend to patients with SCLC, mesothelioma, or thymic
      tumors. Furthermore, in SCLC, encouraging activity was reported for an
      experimental target therapy (rovalpituzumab teserine) and a new chemotherapeutic
      agent (lurbinectedin). For oncogene-addicted NSCLC, next-generation tyrosine
      kinase inhibitors (TKIs) (such as osimertinib or alectinib) have demonstrated
      increased response rates and progression-free survival compared with first
      generation TKIs in patients with both EGFR-mutated and ALK receptor tyrosine
      kinase gene (ALK)-rearranged NSCLC. However, because of the lack of mature
      overall survival data and considering the high efficacy of these drugs in
      patients with NSCLC previously exposed to first- or second-generation TKIs,
      definitive conclusions concerning the best treatment sequence cannot yet be
      drawn. In addition, new oncogenes such as mutant BRAF, tyrosine-protein kinase
      met gene (MET) and erb-b2 receptor tyrosine kinase 2 gene (HER2), and ret proto
      oncogene (RET) rearrangements have joined the list of potential targetable
      drivers. In conclusion, the field of thoracic oncology is on the verge of a
      breakthrough that will open up many promising new therapeutic options for
      physicians and patients. The characterization of biomarkers predictive of
      sensitivity or resistance to immunotherapy and the identification of the optimal
      therapeutic combinations (for ICIs) and treatment sequence (for oncogene-addicted
      NSCLC) represent the toughest upcoming challenges in the domain of thoracic
      oncology.

PMID- 29331647
TI  - The implant effect after intracranial electrode placement: Is transient clinical
      improvement explained by post-implantation electrophysiological changes?

PMID- 29331648
TI  - Lung Ultrasound to Detect Residual Pneumothorax After Chest Drain Removal in Lung
      Resections.
AB  - BACKGROUND: Indication for postdrain removal imaging after lung resection is
      debated. Chest roentgenogram (CR) is widely used to confirm lung expansion but
      not evidence based. We propose to introduce lung ultrasound (LUS) as alternative
      to exclude significant pneumothorax (PTx) in this setting. METHODS: The study
      enrolled 50 patients undergoing lung resections. Inclusion criteria were complete
      expansion of the lung at postoperative CR, pleural effusion of less than 300
      mL/24 h, air leak of 10 to 20 mL/min for 6 hours. Two hours after chest drain
      removal, LUS was performed at the second and third intercostal spaces to assess
      pleural sliding. Patients with no detected PTx or with apical PTx were considered
      for discharge. The same patients were blindly evaluated with CR by a second
      operator, and a comparison between the two methods was performed. Clinical
      decisions were taken based on CR results. RESULTS: LUS confirmed large PTxs in 7
      patients, apical PTxs in 10 patients, and no PTx in 33 patients. CR confirmed 5
      of 7 significant PTxs (1 chest drain reinserted, 4 patients observed), and 2 of 7
      PTx were considered irrelevant. Apical PTxs were confirmed in 8 of 10 patients,
      and in 2 patients there was no PTx at CR. The 33 patients with no PTx at LUS had
      full lung expansion at CR. LUS has a negative predictive value of 100% in
      excluding large PTxs and a positive predictive value of 71%. CONCLUSIONS: In this
      subgroup of patients with air leak of 10 to 20 mL/min, performing an imaging
      study to verify the absence of PTx is desirable; however, when LUS confirms lung
      expansion or the presence of apical PTx, CR does not seem to be needed.

PMID- 29331649
TI  - Friend or foe? Reactive oxygen species production, scavenging and signaling in
      plant response to environmental stresses.
AB  - In the natural environment, plants are exposed to a variety of biotic and abiotic
      stress conditions that trigger rapid changes in the production and scavenging of
      reactive oxygen species (ROS). The production and scavenging of ROS is
      compartmentalized, which means that, depending on stimuli type, they can be
      generated and eliminated in different cellular compartments such as the apoplast,
      plasma membrane, chloroplasts, mitochondria, peroxisomes, and endoplasmic
      reticulum. Although the accumulation of ROS is generally harmful to cells, ROS
      play an important role in signaling pathways that regulate acclimatory and
      defense responses in plants, such as systemic acquired acclimation (SAA) and
      systemic acquired resistance (SAR). However, high accumulations of ROS can also
      trigger redox homeostasis disturbance which can lead to cell death, and in
      consequence, to a limitation in biomass and yield production. Different ROS have
      various half-lifetimes and degrees of reactivity toward molecular components such
      as lipids, proteins, and nucleic acids. Thus, they play different roles in intra-
      and extra-cellular signaling. Despite their possible damaging effect, ROS should
      mainly be considered as signaling molecules that regulate local and systemic
      acclimatory and defense responses. Over the past two decades it has been proven
      that ROS together with non-photochemical quenching (NPQ), hormones, Ca2+ waves,
      and electrical signals are the main players in SAA and SAR, two physiological
      processes essential for plant survival and productivity in unfavorable
      conditions.

PMID- 29331650
TI  - Echocardiographic patterns of postresuscitation myocardial dysfunction.
AB  - BACKGROUND: Postresuscitation myocardial dysfunction (PRMD) can develop after
      successful resuscitation from cardiac arrest. However, echocardiographic patterns
      of PRMD remain unknown. This study aimed to investigate PRMD manifestations with
      serial echocardiography during the post-cardiac arrest period. METHODS: We
      enrolled non-traumatic out-of-hospital cardiac arrest patients older than 19
      years who underwent successful cardiopulmonary resuscitation (CPR). We excluded
      patients with myocardial infarction or pre-existing cardiac disease, including
      heart failure or myocardial disease. Transthoracic echocardiography (TTE) was
      performed within 24 h, between 24 and 48 h, and between 72 and 96 h after
      restoration of spontaneous circulation (ROSC). RESULTS: Of 280 patients, 138 (93
      men) were analysed. PRMD was observed in 45 patients (33%), including global
      dysfunction in 28 patients (20%), regional wall motion abnormalities (RWMA) in 10
      (7%), and Takotsubo pattern in 7 (5%). There were no differences in clinical
      characteristics, laboratory findings, or hospital mortality according to PRMD
      pattern. Global left ventricular (LV) systolic function gradually improved with
      time and had recovered to normal by Day 3 in all patients except one with the
      Takotsubo pattern, which remained on follow-up echocardiography two weeks after
      ROSC. CONCLUSIONS: PRMD occurs in about one-third of patients resuscitated from
      cardiac arrest. Echocardiographic patterns of post-cardiac arrest LV dysfunction
      include global hypokinesia, regional wall motion abnormalities, and Takotsubo
      pattern.

PMID- 29331651
TI  - Activation of p62-keap1-Nrf2 antioxidant pathway in the early stage of
      acetaminophen-induced acute liver injury in mice.
AB  - Acetaminophen (APAP) overdose can cause severe liver failure even death. Nearly
      half of drug-induced liver injury is attributed to APAP in the US and many
      European countries. Oxidative stress has been validated as a critical event
      involved in APAP-induced liver failure. p62/SQSTM1, a selective autophagy adaptor
      protein, is reported to regulate Nrf2-ARE antioxidant pathway in response to
      oxidative stress. However, the exact role of p62-keap1-Nrf2 antioxidant pathway
      in APAP-induced hepatotoxicity remains unknown. In the present study, the dose
      response and time-course model in C57/BL6 mice were established by
      intraperitoneal injection of APAP. The results of serum alanine/aspartate
      aminotransferases (ALT/AST) and histological examination demonstrated that APAP
      overdose resulted in the severe liver injury. In the meantime, the levels of p62,
      phospho-p62 and nuclear Nrf2 were significantly increased by APAP in mice liver,
      suggesting an activation of p62-keap1-Nrf2 pathway. In addition, the expression
      of GSTA1 mRNA was increased in a dose-dependent manner, while the mRNA levels of
      HO-1 and GCLC were decreased with the increase of APAP dose. Our further
      investigation found that expression of HO-1 and GCLC peaked at 3 h~6 h, and then
      were decreased gradually. Taken together, these results indicated that p62-keap1
      Nrf2 antioxidant pathway was primarily activated in the early stage of APAP
      hepatotoxicity, which might play a protective role in the process of APAP-induced
      acute liver injury.

PMID- 29331652
TI  - Salinomycin induces primary chicken cardiomyocytes death via mitochondria
      mediated apoptosis.
AB  - Salinomycin, as a polyether ionophore antibiotic, is extensively used as a feed
      additive against coccidiosis in poultry and as a growth promoter of ruminants
      worldwide. Owing to its narrow therapeutic index, numerous intoxication have been
      reported in target/non-target animals by overdosage, misuse or drug interactions
      as well as human who consumed salinomycin accidently. Salinomycin-induced
      cardiotoxicity in chicken and non-target animals is considered as a major
      contributor to animal death. In the current study, we aim to elucidate the
      underlying mechanism of its myocardial toxicity using primary chicken myocardial
      cell as an in vitro model. The results showed that salinomycin altered cellular
      morphology and induced cell death in a concentration-dependent manner.
      Salinomycin treatment elevated the permeability of the cell membrane and leaded
      to the efflux of enzymes, including creatine kinase (CK) and lactate
      dehydrogenase (LDH). Flow cytometry analysis indicated the number of apoptotic
      cells increased significantly by salinomycin exposure. Furthermore, caspase-3 and
      caspase-9 were activated at gene and protein level rather than caspase-8, along
      with the up-regulation of apoptosis genes Bax, Cytochrome C, Apoptotic peptidase
      activating factor 1 (Apaf-1) and the down-regulation of Bcl-2. Salinomycin
      induced mitochondrial dysfunction was accompanied by the significant decrease of
      mitochondrial membrane potential (MMP) and the severe ultrastructure damage. In
      conclusion, these findings suggest that the toxic dose of salinomycin induces
      severe cardiomyocytes death through mitochondria mediated apoptosis pathway.

PMID- 29331653
TI  - Gallic acid attenuates type I diabetic nephropathy in rats.
AB  - Literature suggests that TGF-beta1 has a central role in the progression of
      diabetic nephropathy and its down regulation can improve the disease condition.
      Oxidative stress, generation of advanced glycation end products and activation of
      renin angiotensin system are the connecting links between hyperglycemia and TGF
      beta1 over expression. Gallic acid is a phytochemical having wide range of
      biological activities. Gallic acid is reported to have antioxidant and advanced
      glycation inhibitory activity. It has also shown inhibitory effects on
      angiotensin converting enzyme. Gallic acid qualifies as a drug candidate to be
      tested in the diabetic nephropathy, one of the important complication of
      diabetes. Streptozotocin (55 mg/kg body weight, i.p.) induced diabetic
      nephropathy was used as an experimental model. Gallic acid was evaluated for its
      possible effect at the dose of 20 and 40 mg/kg body weight. Gallic acid treatment
      significantly lowered plasma levels of the creatinine and blood urea nitrogen and
      elevated the levels of the protein and albumin. Gallic acid also improved
      creatinine clearance. Determination of oxidative stress parameters showed that
      the oxidative stress in kidney tissues was reduced significantly in gallic acid
      treated animals. Results of the plasma, urine and oxidative stress parameters
      were also reflected in the histopathological evaluation showing improvement in
      kidney pathophysiology. ELISA assay for circulating TGF-beta1 evaluation and
      immunohistochemical study for determination of kidney expression of TGF-beta1
      revealed that gallic acid significantly lowered both the circulating and tissue
      levels of TGF-beta1. Results support the hypothesis that gallic acid can be
      effectively used in the treatment of diabetic nephropathy.

PMID- 29331654
TI  - In vitro and in vivo metabolic activation of rhein and characterization of
      glutathione conjugates derived from rhein.
AB  - Rhein (RH), 4,5-dihydroxyanthrauinone-2-carboxylic acid, is found in rhubarb
      (Dahuang), a traditional herbal medicine. RH has reportedly demonstrated multiple
      pharmacologic properties. Previous studies have also shown that RH induced
      hepatotoxicity, but the mechanisms of the adverse effect remain unknown. The
      major objective of the present study was to study the metabolic pathways of RH in
      order to identify potential reactive metabolites. One mono-hydroxylation
      metabolite (M1) was detected in urine and bile of rats given RH. M1 was also
      observed in rat and human liver microsomal incubations after exposure to RH. A
      total of three (GSH) conjugates (M2, M3 and M5) were detected in bile of rats
      treated with RH. We concluded that M2-M3 were directly derived from parent
      compound RH through spontaneous reaction with GSH. M5 was derived from M1 by
      reaction with GSH, which required cytoslic GSTs. M5 was further metabolized to
      the corresponding NAC conjugate (mercapturic acid) and was excreted in urine.
      P450 2C9 was mainly involved in the oxidation of RH.

PMID- 29331655
TI  - What makes it so difficult for nurses to coach patients in shared decision
      making? A process evaluation.
AB  - BACKGROUND: Primary care nurses play a crucial role in coaching patients in
      shared decision making about goals and actions. This presents a challenge to
      practice nurses, who are frequently used to protocol-based working routines.
      Therefore, an approach was developed to support nurses to coach patients in
      shared decision making. OBJECTIVES: To investigate how the approach was
      implemented and experienced by practice nurses and patients. DESIGN: A process
      evaluation was conducted using quantitative and qualitative methods.
      SETTINGS/PARTICIPANTS: Fifteen female practice nurses (aged between 28 and 55
      years), working with people suffering from diabetes, COPD, asthma and/or
      cardiovascular diseases, participated. Nurses were asked to apply the approach to
      their chronically ill patients and to recruit patients (n = 10) willing to
      participate in an interview or an audio-recording of a consultation (n = 13);
      patients (13 women, 10 men) were aged between 41 and 88 years and suffered from
      diabetes, COPD or cardiovascular diseases. METHODS: The approach involved a
      framework for shared decision making about goals and actions, a tool to explore
      the patient perspective, a patient profiles model and a training course.
      Interviews (n = 15) with nurses, a focus group with nurses (n = 9) and interviews
      with patients (n = 10) were conducted. Nurses filled in a questionnaire about
      their work routine before, during and after the training course. They were asked
      to deliver audiotapes of their consultations (n = 13). RESULTS: Overall, nurses
      felt that the approach supported them to coach patients in shared decision
      making. Nurses had become more aware of their own attitudes and learning needs
      and reported to have had more in-depth discussions with patients. The on-the-job
      coaching was experienced as valuable. However, nurses struggled to integrate the
      approach in routine care. They experienced the approach as different to their
      protocol-based routines and expressed the importance of receiving support and the
      need for integration of the approach into the family physician practice.
      CONCLUSION: This study shows that changing practice nurses' role from medical
      experts to coaches in shared decision making is very complex and requires paying
      attention to skills and attitudes, as well as to contextual factors. Our results
      indicate that more time and training might be needed for this role transition.
      Moreover, it might be worthwhile to focus on organizational learning, in order to
      increase an organization's capacity to change work routines in a collaborative
      process. Future research into the development and evaluation of health coaching
      approaches, focusing on shared decision making, is necessary.

PMID- 29331656
TI  - Effect of a wearable patient sensor on care delivery for preventing pressure
      injuries in acutely ill adults: A pragmatic randomized clinical trial (LS-HAPI
      study).
AB  - IMPORTANCE: Though theoretically sound, studies have failed to demonstrate the
      benefit of routine repositioning of at-risk patients for the prevention of
      hospital acquired pressure injuries. OBJECTIVE: To assess the clinical
      effectiveness of a wearable patient sensor to improve care delivery and patient
      outcomes by increasing the total time with turning compliance and preventing
      pressure injuries in acutely ill patients. DESIGN: Pragmatic, investigator
      initiated, open label, single site, randomized clinical trial. SETTING: Two
      Intensive Care Units in a large Academic Medical Center in California.
      PARTICIPANTS: Consecutive adult patients admitted to one of two Intensive Care
      Units between September 2015 to January 2016 were included (n = 1564). Of the
      eligible patients, 1312 underwent randomization. INTERVENTION: Patients received
      either turning care relying on traditional turn reminders and standard practices
      (control group, n = 653), or optimal turning practices, influenced by real-time
      data derived from a wearable patient sensor (treatment group, n = 659). MAIN
      OUTCOME(S) AND MEASURE(S): The primary and secondary outcomes of interest were
      occurrence of hospital acquired pressure injury and turning compliance.
      Sensitivity analysis was performed to compare intention-to-treat and per-protocol
      effects. RESULTS: The mean age was 60 years (SD, 17 years); 55% were male. We
      analyzed 103,000 h of monitoring data. Overall the intervention group had
      significantly fewer Hospital Acquired Pressure Injuries during Intensive Care
      Unit admission than the control group (5 patients [0.7%] vs. 15 patients [2.3%]
      (OR = 0.33, 95%CI [0.12, 0.90], p = 0.031). The total time with turning
      compliance was significantly different in the intervention group vs. control
      group (67% vs 54%; difference 0.11, 95%CI [0.08, 0.13], p < 0.001). Turning
      magnitude (21 degrees , p = 0.923) and adequate depressurization time (39%, p =
      0.145) were not statistically different between groups. CONCLUSIONS AND
      RELEVANCE: Among acutely ill adult patients requiring Intensive Care Unit
      admission, the provision of optimal turning was greater with a wearable patient
      sensor, increasing the total time with turning compliance and demonstrated a
      statistically significant protective effect against the development of hospital
      acquired pressure injuries. These are the first quantitative data on turn quality
      in the Intensive Care Unit and highlight the need to reinforce optimal turning
      practices. Additional clinical trials leveraging technologies like wearable
      sensors are needed to establish the appropriate frequency and dosing of
      individualized turning protocols to prevent pressure injuries in at-risk
      hospitalized patients.

PMID- 29331657
TI  - Views of teenage children about the effects of a Parent's mobility disability.
AB  - BACKGROUND: Few U.S. studies have explored how children experience a parent's
      mobility disability and its effects on their daily lives. OBJECTIVE: We aimed to
      engage youth ages 13-17 who had at least one parent with mobility disability in
      describing their perceptions of their parent's disability and its consequences
      for their daily and family life. METHODS: Participants videoed and photographed
      their experiences following general guidelines from the researchers about topics
      of interest. Participants made their own choices about what they submitted. We
      used conventional content analysis to identify broad themes. RESULTS: The mean
      (standard deviation) age of the 10 participants was 15.2 (1.9) years; 5 were
      male; 9 participants were white. All 5 girls submitted multiple self-focused
      (selfie) videos made in their bedrooms; the 5 boys submitted more diverse data
      files. Several broad themes or topics emerged including: the effects of timing
      and trajectory of the parent's disability; perceptions of early maturity and
      responsibility; fears and frustrations relating to the parent's disability;
      support and emerging resilience; and sense of social justice. Participants
      generally felt their parents' disability made them become - compared to their
      peers - more mature, responsible, capable of performing household tasks, and
      aware of disability civil rights. CONCLUSIONS: Participants raised many issues
      that health care providers should be aware of when youth have parents with
      mobility disability. A parent's mobility disability may be associated with
      resilience but also may pose challenges for youth. More research is needed to
      understand better adolescents' experiences and how clinicians might best assist
      these youth.

PMID- 29331659
TI  - Mindfulness-related differences in neural response to own infant negative versus
      positive emotion contexts.
AB  - Mindfulness is thought to promote well-being by shaping the way people respond to
      challenging social-emotional situations. Current understanding of how this occurs
      at the neural level is based on studies of response to decontextualized emotion
      stimuli that may not adequately represent lived experiences. In this study, we
      tested relations between mothers' dispositional mindfulness and neural responses
      to their own infant in different emotion-eliciting contexts. Mothers (n = 25)
      engaged with their 3-month-old infants in videorecorded tasks designed to elicit
      negative (arm restraint) or positive (peekaboo) emotion. During a functional MRI
      session, mothers were presented with 15-s clips from these recordings, and
      dispositional mindfulness scores were used to predict their neural responses to
      arm restraint > peekaboo videos. Mothers higher in nonreactivity showed
      relatively lower activation to their infants' arm restraint compared to peekaboo
      videos in hypothesized regions-insula and dorsal prefrontal cortex-as well as non
      hypothesized regions. Other mindfulness dimensions were associated with more
      limited areas of lower (nonjudgment) and higher (describing) activation in this
      contrast. Mothers who were higher in mindfulness generally activated more to the
      positive emotion context and less to the negative emotion context in perceptual
      and emotion processing areas, a pattern that may help to explain mindfulness
      related differences in well-being.

PMID- 29331658
TI  - Sulforaphene Enhances The Efficacy of Photodynamic Therapy In Anaplastic Thyroid
      Cancer Through Ras/RAF/MEK/ERK Pathway Suppression.
AB  - Sulforaphene (SFE), a natural isothiocyanate from cruciferous vegetables has
      shown a potential anticancer effect against cervical and lung cancer. Palliative
      treatments like photodynamic therapy (PDT) are being implemented for a long time
      however, the results are still not promising in case of aggressive cancers like
      anaplastic thyroid cancer. The objective of this work is to establish an
      alternative method with the combination of photofrin-PDT and sulforaphene, a
      natural isothiocyanate from cruciferous vegetables, against human anaplastic
      thyroid cancer to enhance the efficacy of PDT. In this study, cell viability of
      FRO cells due to combination treatment was analyzed by MTT assay, Cell cycle
      arrest, MMP depolarization and ROS generation, analyzed by flow cytometry.
      Western blot analysis of various proliferative proteins was performed to assess
      the activity of combination treatment against FRO cells. From the results,
      sulforaphene alone showed no cytotoxicity against normal cells, however,
      combination of sulforaphene and photofrin mediated PDT showed a noticeable
      decrease in cell proliferation against FRO cells. Combination treatment
      synergistically caused cell cycle arrest via ROS generation and MMP
      depolarization. The expressions of Ras, MEK, ERK, B-Raf proteins significantly
      modulated due to combination treatment. PDT and SFE can induce apoptosis in
      anaplastic thyroid cancer cells individually but while treated in combination, it
      enhanced the apoptotic and anti-proliferative effect, much higher than the
      individual doses. In summary, our work designates sulforaphene as a unique
      natural enhancer of efficacy with PDT against anaplastic thyroid cancer.

PMID- 29331660
TI  - Persistent contamination of heater-cooler units for extracorporeal circulation
      cured by chlorhexidine-alcohol in water tanks.
AB  - Recently, surgical site infections due to non-tuberculous mycobacteria (NTM) have
      been linked to heater-cooler unit contamination. The European Centre for Disease
      Prevention and Control and manufacturers now recommend the use of hydrogen
      peroxide in filtered water to fill heater-cooler unit tanks. After implementation
      of these measures in our hospital, heater-cooler units became heavily
      contaminated by opportunistic waterborne pathogens such as Pseudomonas aeruginosa
      and Stenotrophomonas maltophilia. No NTM were detected but fast-growing resistant
      bacteria could impair their detection. The efficiency of hydrogen peroxide and
      chlorhexidine-alcohol was compared in situ. Chlorhexidine-alcohol treatment
      stopped waterborne pathogen contamination and NTM were not cultured whereas their
      detection efficiency was probably improved.

PMID- 29331661
TI  - Effect of LaF3: Ag fluorescent nanoparticles on photodynamic efficiency and
      cytotoxicity of Protoporphyrin IX photosensitizer.
AB  - LaF3: Ag nanoparticles (NPs) were synthesized by the co-precipitation method. The
      produced NPs were characterized by X-ray diffraction (XRD) pattern, scanning
      electron microscope (SEM), dynamic light scattering (DLS) and Fourier transform
      infrared spectroscopy (FTIR). The emission spectrum of LaF3:Ag NPs is mostly
      overlapped with the absorption band of protoporphyrin IX (PpIX) and their
      conjugation was confirmed by studying fluorescence resonance energy transfer
      (FRET) from LaF3:Ag donor to protoporphyrin IX acceptor. The energy transfers
      from LaF3:Ag NPs to photosensitizer molecules is very efficient. So, the produced
      LaF3:Ag NPs can be recommended as light source for photodynamic therapy (PDT).
      The thiol group of cysteine was bound to LaF3:Ag NPs in order to conjugate
      LaF3:Ag NPs and protoporphyrin IX. UVC light source was used to excite
      fluorescent LaF3:Ag NPs. The reactive oxygen species (ROS) produced by
      photosensitizer was identified using special fluorescent probes (anthracene,
      methylene blue and methyl orange) as detectors.

PMID- 29331662
TI  - Exposure to natural environments, and photographs of natural environments,
      promotes more positive body image.
AB  - Five studies were conducted to understand the impact of nature exposure on body
      image. In three studies using different designs and outcome measures, British
      university students were exposed to photographs of natural or built environments.
      Results indicated that exposure to images of natural, but not built, environments
      resulted in improved state body image. In Study 4, British community participants
      went on a walk in a natural or built environment, with results indicating that
      the walk in a natural environment resulted in significantly higher state body
      appreciation, whereas the walk in a built environment resulted in significantly
      lower scores. In Study 5, British participants were recruited as they were
      entering a designed green space on their own volition. Results indicated that
      spending time in the green space led to improved state body appreciation. These
      results indicate that exposure to isomorphic or in-situ natural environments has
      positive effects on state body image.

PMID- 29331663
TI  - A Multicenter Randomized Trial to Evaluate Hematologic Toxicities after
      Hyperthermic Intraperitoneal Chemotherapy with Oxaliplatin or Mitomycin in
      Patients with Appendiceal Tumors.
AB  - BACKGROUND: Appendiceal cancer is a rare disease that has proven difficult to
      study in prospective trials. Cytoreductive surgery with hyperthermic
      intraperitoneal chemotherapy (HIPEC) is an established therapy for peritoneal
      dissemination from appendiceal cancer. The optimal chemotherapeutic agent to use
      in the HIPEC is not clear. Mitomycin has long been used, however, our previous
      phase I experience and European retrospective studies suggest oxaliplatin as an
      alternative. Therefore, we initiated a multicenter randomized trial to compare
      mitomycin with oxaliplatin HIPEC for appendiceal cancer. STUDY DESIGN: Patients
      with mucinous appendiceal neoplasms with evidence of peritoneal dissemination
      underwent cytoreductive surgery and HIPEC using a closed technique for 120
      minutes. Patients were randomized intraoperatively to HIPEC using mitomycin (40
      mg) or oxaliplatin (200 mg/M2). Follow-up included daily blood counts and
      toxicity assessments. RESULTS: One hundred and twenty-one analytic patients were
      accrued to the trial during 6 years at 3 sites. The patients were 57% female,
      with a mean age of 55.3 years (range 22 to 82 years). The disease was low grade
      in 77% and high grade in 23%. There were no significant differences in hemoglobin
      or platelet counts. The WBC was significantly lower in the mitomycin group
      between postoperative days 5 and 10. Overall and disease-free survival rates at 3
      years were similar at 83.7% and 66.8% for mitomycin and 86.9% and 64.8% for
      oxaliplatin. CONCLUSIONS: This represents the first completed prospective
      randomized trial for cancer of the appendix, and shows that multicenter trials
      for this disease are feasible. Both mitomycin and oxaliplatin are associated with
      minor hematologic toxicity. However, mitomycin has slightly higher hematologic
      toxicity and lower quality of life than oxaliplatin in HIPEC. Consequently,
      oxaliplatin might be preferred in patients with leukopenia and mitomycin
      preferred in patients with thrombocytopenia due to earlier chemotherapy.

PMID- 29331664
TI  - Children exhibit different performance patterns in explicit and implicit theory
      of mind tasks.
AB  - Three studies tested scope and limits of children's implicit and explicit theory
      of mind. In Studies 1 and 2, three- to six-year-olds (N = 84) were presented with
      closely matched explicit false belief tasks that differed in whether or not they
      required an understanding of aspectuality. Results revealed that children
      performed equally well in the different tasks, and performance was strongly
      correlated. Study 3 tested two-year-olds (N = 81) in implicit interactive
      versions of these tasks and found evidence for dis-unity: children performed
      competently only in those tasks that did not require an understanding of
      aspectuality. Taken together, the present findings suggest that early implicit
      and later explicit theory of mind tasks may tap different forms of cognitive
      capacities.

PMID- 29331665
TI  - Blocking LPA-dependent signaling increases ovarian cancer cell death in response
      to chemotherapy.
AB  - The paradoxical role of reactive oxygen species in cell death versus cell
      survival establishes a delicate balance between chemotherapy efficacy and
      management of detrimental side effects. Normal proliferative signaling requires
      that cells remain inside a redox range that allows reversible protein oxidation
      to occur. Shifting the redox environment toward highly reducing or oxidizing
      states leads to cellular stress and cell death. Reactive oxygen species produced
      in response to Taxol and cisplatin treatment are necessary for effective cancer
      cell killing but the same ROS leads to damaging side effects in normal tissues.
      Combining antioxidants with chemotherapeutics to alleviate the unwanted side
      effects produces variable and often undesirable effects on cancer treatment.
      Here, we describe a more targeted method to improve ovarian cancer cell killing
      without the need for antioxidants. In ovarian cancer cells, lysophosphatidic acid
      (LPA) is a prominent growth factor that contributes to tumor survival and
      proliferation. We find that blocking LPA-dependent signaling with a specific
      receptor antagonist consistently increases cell death in response to both Taxol
      and cisplatin. We propose that inhibiting the upregulated growth factor-dependent
      signaling in cancer cells will target chemo-insensitivity, potentially lowering
      the necessary dose of the drugs and preventing harmful side effects.

PMID- 29331667
TI  - Vitamin D suppresses macrophage infiltration by down-regulation of TREM-1 in
      diabetic nephropathy rats.
AB  - This study intends to investigate the effect of active vitamin D (VD) on the
      expression of triggering receptor expressed on myeloid cells-1 (TREM-1) in the
      renal tissues of diabetic nephropathy (DN) rats and to explore the impact of TREM
      1 on macrophage adhesion and migration. We find that the expressions of TREM-1
      and CD68 protein are higher in DN rats compared with rats in the normal control
      group and that these changes are decreased in the DN + VD group. In vitro, the
      capacity for macrophage adhesion and migration and the expression of TREM-1 are
      increased under high-glucose conditions, but VD inhibits this progress. TREM-1
      siRNA decreases high-glucose-induced macrophage adhesion and migration, whereas
      over-expression of TREM-1 inhibits its action. However, VD cannot suppress high
      glucose-induced TREM-1 expression and macrophage adhesion and migration when TREM
      1 is over-expressed. These results demonstrate that VD can suppress macrophage
      adhesion and migration by reducing the expression of TREM-1.

PMID- 29331668
TI  - Earlier and enhanced rehabilitation of mechanically ventilated patients in
      critical care: A feasibility randomised controlled trial.
AB  - BACKGROUND: Systematic reviews of early rehabilitation within intensive care
      units have highlighted the need for robust multi-centre randomised controlled
      trials with longer term follow up. This trial aims to explore the feasibility of
      earlier and enhanced rehabilitation for patients mechanically ventilated for
      >=5days and to assess the impact on possible long term outcome measures for use
      in a definitive trial. METHODS: Patients admitted to a large UK based intensive
      care unit and invasively ventilated for >=5days were randomised to the
      rehabilitation intervention or standard care on a 1:1 basis, stratified by age
      and SOFA score. The rehabilitation intervention involved a structured programme,
      with progression along a functionally based mobility protocol according to set
      safety criteria. RESULTS: 103 out of 128 eligible patients were recruited into
      the trial, achieving an initial recruitment rate of 80%. Patients in the
      intervention arm mobilized significantly earlier (8days vs 10 days, p=0.035), at
      a more acute phase of illness (SOFA 6 vs 4, p<0.05) and reached a higher level of
      mobility at the point of critical care discharge (MMS 7 vs 5, p<0.01).
      CONCLUSION: We have demonstrated the feasibility of introducing a structured
      programme of rehabilitation for patients admitted to critical care.

PMID- 29331666
TI  - Age-related oxidative changes in pancreatic islets are predominantly located in
      the vascular system.
AB  - Aged tissues usually show a decreased regenerative capacity accompanied by a
      decline in functionality. During aging pancreatic islets also undergo several
      morphological and metabolic changes. Besides proliferative and regenerative
      limitations, endocrine cells lose their secretory capacity, contributing to a
      decline in functional islet mass and a deregulated glucose homeostasis. This is
      linked to several features of aging, such as induction of cellular senescence or
      the formation of modified proteins, such as advanced glycation end products
      (AGEs) - the latter mainly examined in relation to hyperglycemia and in disease
      models. However, age-related changes of endocrine islets under normoglycemic and
      non-pathologic conditions are poorly investigated. Therefore, a characterization
      of pancreatic tissue sections as wells as plasma samples of wild-type mice
      (C57BL/6J) at various age groups (2.5, 5, 10, 15, 21 months) was performed. Our
      findings reveal that mice at older age are able to secret sufficient amounts of
      insulin to maintain normoglycemia. During aging the pancreatic islet area
      increased and the islet size doubled in 21 months old mice when compared to 2.5
      months old mice, whereas the islet number was unchanged. This was accompanied by
      an age-dependent decrease in Ki-67 levels and pancreatic duodenal homeobox-1 (PDX
      1), indicating a decline in proliferative and regenerative capacity of pancreatic
      islets with advancing age. In contrast, the number of p16Ink4a-positive nuclei
      within the islets was elevated starting from 10 months of age. Interestingly,
      AGEs accumulated exclusively in the islet blood vessels of old mice associated
      with increased amounts of inflammatory markers, such as the inducible nitric
      oxide synthase (iNOS) and 3-nitrotyrosine (3-NT). In summary, the age-related
      increase in islet size and area was associated with the induction of senescence,
      accompanied by an accumulation of non-enzymatically modified proteins in the
      islet vascular system.

PMID- 29331669
TI  - Acinetobacter baumannii ST317 can be identified with Martins' trilocus sequence
      based multiplex-PCR.

PMID- 29331670
TI  - Circulation of Alphacoronavirus, Betacoronavirus and Paramyxovirus in
      Hipposideros bat species in Zimbabwe.
AB  - Bats carry a great diversity of zoonotic viruses with a high-impact on human
      health and livestock. Since the emergence of new coronaviruses and
      paramyxoviruses in humans (e.g. Severe Acute Respiratory Syndrome Coronavirus
      (SARS-CoV) and Nipah virus), numerous studies clearly established that bats can
      maintain some of these viruses. Improving our understanding on the role of bats
      in the epidemiology of the pathogens they harbour is necessary to prevent cross
      species spill over along the wild/domestic/human gradient. In this study, we
      screened bat faecal samples for the presence of Coronavirus and Paramyxovirus in
      two caves frequently visited by local people to collect manure and/or to hunt
      bats in Zimbabwe. We amplified partial RNA-dependent RNA polymerase genes of
      Alpha and Betacoronavirus together with the partial polymerase gene of
      Paramyxovirus. Identified coronaviruses were related to pathogenic human strains
      and the paramyxovirus belonged to the recently described Jeilongvirus genus. Our
      results highlighted the importance of monitoring virus circulation in wildlife,
      especially bats, in the context of intense human-wildlife interfaces in order to
      strengthen prevention measures among local populations and to implement sentinel
      surveillance in sites with high zoonotic diseases transmission potential.

PMID- 29331671
TI  - The molecular characteristics of avian influenza viruses (H9N2) derived from air
      samples in live poultry markets.
AB  - OBJECTIVE: To study the molecular characteristics of H9N2-subtype avian influenza
      viruses (AIVs) isolated from air samples collected in live poultry markets (LPMs)
      and explore their sequence identities with AIVs that caused human infection.
      METHODS: Weekly surveillance of H9N2-subtype AIVs in the air of LPMs was
      conducted from 2015 to 2016. H9-positive samples were isolated from chicken
      embryos. Whole genome sequences of the isolated AIVs were obtained through high
      throughput sequencing. Phylogenetic analysis and key loci variations of the
      sequences were further analyzed. RESULTS: A total of 327 aerosol samples were
      collected from LPMs. Nine samples were positive for H9-subtype AIVs based on
      quantitative real-time reverse transcription polymerase chain reaction (qRRT
      PCR). According to the whole genome sequence analysis and phylogenetic analysis,
      except for the A/Environment/Zhongshan/ZS201505/2015 (ZS201505) strain, 8 gene
      segments of 8 aerosol H9N2 isolates and 2 H9N2 human isolates in 2015 were
      located in the same clade. Among key loci variations, except for the ZS201505
      strain, H9N2-subtype AIVs had no mutations in eight receptor binding sites of
      hemagglutinin (HA), and stalks of neuraminidase (NA) proteins exhibited a
      deletion site of three bases. The PA gene of ZS201503 and ZS201602 exhibited an
      L336M mutation. The N30D and T215A mutations in the M1 gene and amino acid
      residues L89V in PB2, P42S in NS1 and S31N in M2 were retained in these 9 strains
      of H9N2 isolates, which could enhance the virus's virulence. CONCLUSION: Live
      H9N2 AIVs survived in the aerosol of LPMs in Zhongshan City. The aerosol viruses
      had a close evolutionary relationship with human epidemic strains, indicating
      that there might be a risk of AIV transmission from polluted aerosols in LPMs to
      humans. Mutations in H9N2-subtype AIVs isolated from air samples collected from
      LPMs suggested their pathogenicity was enhanced to infect humans.

PMID- 29331672
TI  - Breast cancer screening: Where have we been and where are we going? A personal
      perspective based on history, data and experience.
AB  - It is important to understand the history of breast cancer screening to better
      understand the continuing effort to reduce access to screening. Since the
      randomized, controlled trials have shown a statistically significant mortality
      reduction for women ages 40-74, the appropriate threshold for initiating
      screening is age 40 with no data to support the use of the age of 50 as a
      threshold for screening. All women are at risk for developing breast cancer and
      all women should have access to screening.

PMID- 29331673
TI  - Diversity of Aspergillus section Nigri on the surface of Vitis labrusca and its
      hybrid grapes.
AB  - This study investigated the presence of Aspergillus species belonging to
      Aspergillus section Nigri on Vitis labrusca and its hybrid grapes grown in
      Brazil. The ability of the fungi isolates to produce ochratoxin A (OTA) and
      fumonisin B2 (FB2) as well as the presence of these mycotoxins in the grapes were
      also studied. Eighty-eight samples were collected from the main grape producing
      states in Brazil: Rio Grande do Sul (n=30), Pernambuco (n=21), Sao Paulo (n=21)
      and Parana (n=16). The highest average contamination level by A. section Nigri
      occurred on the grapes from Pernambuco (66.3%). A total of 2042 A. section Nigri
      isolates was analyzed and clustered in three groups according to morphology
      characterization: A. section Nigri uniseriate (79.3%), A. niger "aggregate"
      (18.3%) and A. carbonarius (2.4%). In order to precisely identify the Aspergillus
      species, two hundred and forty-eight strains were subjected to DNA sequencing.
      Among the A. section Nigri uniseriate group, the following species were found: A.
      japonicus, A. uvarum, A. brunneoviolaceus, A. aculeatus and A. labruscus. Within
      the A. niger "aggregate", the following species were found: A.niger sensu
      stricto, A. welwitschiae and A. vadensis. Regarding mycotoxin-production
      capacity, 3.2% of the total A. section Nigri isolates (2042) were positive for
      OTA production and from A. niger "aggregate" (373) tested, 42.1% were FB2
      producers. However, none of the 88 grape samples were contaminated with these
      mycotoxins.

PMID- 29331674
TI  - HIV Activates the Tyrosine Kinase Hck to Secrete ADAM Protease-Containing
      Extracellular Vesicles.

PMID- 29331676
TI  - Identification of novel amino acid residues of influenza virus PA-X that are
      important for PA-X shutoff activity by using yeast.
AB  - The influenza A virus protein PA-X comprises an N-terminal PA region and a C
      terminal PA-X-specific region. PA-X suppresses host gene expression, termed
      shutoff, via mRNA cleavage. Although the endonuclease active site in the N
      terminal PA region of PA-X and basic amino acids in the C-terminal PA-X-specific
      region are known to be important for PA-X shutoff activity, other amino acids may
      also play a role. Here, we used yeast to identify novel amino acids of PA-X that
      are important for PA-X shutoff activity. Unlike wild-type PA-X, most PA-X mutants
      predominantly localized in the cytoplasm, indicating that these mutations
      decreased the shutoff activity of PA-X by affecting PA-X translocation to the
      nucleus. Mapping of the identified amino acids onto the N-terminal structure of
      PA revealed that some of them likely contribute to the formation of the
      endonuclease active site of PA.

PMID- 29331675
TI  - Module Analysis Captures Pancancer Genetically and Epigenetically Deregulated
      Cancer Driver Genes for Smoking and Antiviral Response.
AB  - : The availability of increasing volumes of multi-omics profiles across many
      cancers promises to improve our understanding of the regulatory mechanisms
      underlying cancer. The main challenge is to integrate these multiple levels of
      omics profiles and especially to analyze them across many cancers. Here we
      present AMARETTO, an algorithm that addresses both challenges in three steps.
      First, AMARETTO identifies potential cancer driver genes through integration of
      copy number, DNA methylation and gene expression data. Then AMARETTO connects
      these driver genes with co-expressed target genes that they control, defined as
      regulatory modules. Thirdly, we connect AMARETTO modules identified from
      different cancer sites into a pancancer network to identify cancer driver genes.
      Here we applied AMARETTO in a pancancer study comprising eleven cancer sites and
      confirmed that AMARETTO captures hallmarks of cancer. We also demonstrated that
      AMARETTO enables the identification of novel pancancer driver genes. In
      particular, our analysis led to the identification of pancancer driver genes of
      smoking-induced cancers and 'antiviral' interferon-modulated innate immune
      response. SOFTWARE AVAILABILITY: AMARETTO is available as an R package at
      https://bitbucket.org/gevaertlab/pancanceramaretto.

PMID- 29331677
TI  - Identification of Potential MR-Derived Biomarkers for Tumor Tissue Response to
      177Lu-Octreotate Therapy in an Animal Model of Small Intestine Neuroendocrine
      Tumor.
AB  - Magnetic resonance (MR) methods enable noninvasive, regional tumor therapy
      response assessment, but associations between MR parameters, underlying biology,
      and therapeutic effects must be investigated. The aim of this study was to
      investigate response assessment efficacy and biological associations of MR
      parameters in a neuroendocrine tumor (NET) model subjected to radionuclide
      treatment. Twenty-one mice with NETs received 177Lu-octreotate at day 0. MR
      experiments (day -1, 1, 3, 8, and 13) included T2-weighted, dynamic contrast
      enhanced (DCE) and diffusion-weighted imaging (DWI) and relaxation measurements
      (T1/T2*). Tumor tissue was analyzed using proteomics. MR-derived parameters were
      evaluated for each examination day and for different radial distances from the
      tumor center. Response assessment efficacy and biological associations were
      evaluated using feature selection and protein expression correlations,
      respectively. Reduced tumor growth rate or shrinkage was observed until day 8,
      followed by reestablished growth in most tumors. The most important MR parameter
      for response prediction was DCE-MRI-derived pretreatment signal enhancement ratio
      (SER) at 40% to 60% radial distance, where it correlated significantly also with
      centrally sampled protein CCD89 (association: DNA damage and repair,
      proliferation, cell cycle arrest). The second most important was changed
      diffusion (D) between day -1 and day 3, at 60% to 80% radial distance, where it
      correlated significantly also with peripherally sampled protein CATA
      (association: oxidative stress, proliferation, cell cycle arrest, apoptotic cell
      death). Important information regarding tumor biology in response to radionuclide
      therapy is reflected in several MR parameters, SER and D in particular. The
      spatial and temporal information provided by MR methods increases the sensitivity
      for tumor therapy response.

PMID- 29331678
TI  - MicroRNA-320 Enhances Radiosensitivity of Glioma Through Down-Regulation of
      Sirtuin Type 1 by Directly Targeting Forkhead Box Protein M1.
AB  - Glioma is the most common cancer in human brain system and seriously threatens
      human health. miRNA-320 has been demonstrated to be closely correlated with the
      development of glioma. However, its effect and molecular mechanism underlying
      radioresistance have not been fully elucidated in glioma. Here, RT-qPCR assay was
      used to assess the expressions of miR-320 and forkhead box protein M1 (FoxM1)
      mRNA in glioma tumor tissues and cells. The effects of miR-320, FoxM1 and sirtuin
      type 1 (Sirt1) on radiosensitivity in glioma cells were evaluated by clone
      formation assay, apoptosis assay, histone H2AX phosphorylation level (gammaH2AX)
      detection and caspase 3 activity analysis, respectively. The direct interaction
      between miR-320 and FoxM1 was detected by luciferase assay. The protein levels of
      FoxM1, Sirt1 and gammaH2AX were measured by western blot assay. We found that miR
      320 expression was down-regulated and FoxM1 expression was up-regulated in
      radioresistant glioma tissues and IR-treated glioma cells. miR-320 overexpression
      dramatically enhanced radiosensitivity, promoted apoptosis, and improved
      gammaH2AX expression and caspase 3 activity in glioma cells. Luciferase reporter
      assay and western blot assay further validated that miR-320 suppressed FoxM1
      expression by directly targeting 3' UTR region of FoxM1. Moreover, miR-320
      inhibited Sirt1 expression via targeting FoxM1 in glioma cells. Furthermore,
      overexpression of FoxM1 and Sirt1 strikingly attenuated miR-320-induced increase
      of radiosensitivity, apoptosis and gammaH2AX expression in glioma cells. In
      conclusion, miR-320 enhanced radiosensitivity of glioma cells through down
      regulation of Sirt1 by directly targeting FoxM1.

PMID- 29331679
TI  - Molecular identification of forensically important calliphoridae and
      sarcophagidae species using ITS2 nucleotide sequences.
AB  - The application of insect evidence to forensic investigations is mainly based on
      the estimation of postmortem interval and the identification of insect species
      from samples that are collected from the crime scene. Due to the limited number
      of expert taxonomists, species identification is one of the major barriers for
      crime scene investigators to utilize forensic entomology. Therefore, the
      molecular identification of species, using mitochondrial cytochrome c oxidase
      subunit I (COI) gene, has been suggested as an alternative strategy. However, in
      some cases, these maternally inherited markers cause confusion; hence, nuclear
      DNA markers such as ITS2 are also required as supporting tools. Eleven
      Calliphoridae and 5 Sarcophagidae fly species collected from Korea were utilized
      for PCR amplification and nucleotide sequencing of ITS2 locus. Species Identifier
      software was used for sequence analysis and comparison. The results demonstrated
      that 11 Korean Calliphoridae and 5 Korean Sarcophagidae fly species could be
      distinguished using ITS2 nucleotide sequences. In particular, the sister species,
      Lucilia illustris and Lucilia caesar were also distinguished, despite the very
      low level of interspecific diversity. However, when compared with previously
      reported ITS2 nucleotide sequences, several identification failures were noted.
      This is the first study that widely analyzed nucleotide sequences of the ITS2
      locus from Calliphoridae and Sarcophagidae fly species collected in Korea.

PMID- 29331681
TI  - Endogenous cortisol in keratinized matrices: Systematic determination of baseline
      cortisol levels in hair and the influence of sex, age and hair color.
AB  - The measurement of hair cortisol is increasingly used to measure long-term
      cumulative cortisol levels and investigate its role as an important stress
      mediator. In this study a comparative statistical analysis of five independent
      studies (all analyzed in our laboratory) was performed to investigate baseline
      ranges of cortisol values in hair and evaluate potential influences of sex, age
      and hair color. Cortisol concentrations in hair of 554 subjects were measured and
      a comparative statistical analysis was performed. The analysis showed that
      cortisol levels significantly differ depending on age. The toddler group (7
      months (0.6 years) to 3 years) showed significantly higher values (median
      10pg/mg, p-value<0.0001, d=0.78) than the adolescent group. The adolescent groups
      showed significantly lower (p-value<0.0001, d=0.58 and p<0.0001, d=0.13) values
      (median 2.4pg/mg and 2.8pg/mg) than the adult group (median 5.8pg/mg).
      Furthermore, in the adult group men showed significantly higher cortisol values
      than women (p-value<0.05, d=0.17). This effect could not be seen in the
      adolescent group. Black hair showed higher cortisol concentrations than blond
      hair (p-value<0.0001, d=1.3). In addition, two rounds of interlaboratory
      comparisons for hair cortisol samples between four laboratories revealed very
      consistent results. Our results demonstrate that baseline cortisol levels are
      generally low in hair thus making a standardized and well-elaborated analytical
      method indispensable for accurate determination. Age-dependent normative baseline
      cortisol levels (toddlers, adolescents and adults) are highly recommended based
      on the comparative analysis comprising five independent studies.

PMID- 29331680
TI  - Estimating error rates for firearm evidence identifications in forensic science.
AB  - Estimating error rates for firearm evidence identification is a fundamental
      challenge in forensic science. This paper describes the recently developed
      congruent matching cells (CMC) method for image comparisons, its application to
      firearm evidence identification, and its usage and initial tests for error rate
      estimation. The CMC method divides compared topography images into correlation
      cells. Four identification parameters are defined for quantifying both the
      topography similarity of the correlated cell pairs and the pattern congruency of
      the registered cell locations. A declared match requires a significant number of
      CMCs, i.e., cell pairs that meet all similarity and congruency requirements.
      Initial testing on breech face impressions of a set of 40 cartridge cases fired
      with consecutively manufactured pistol slides showed wide separation between the
      distributions of CMC numbers observed for known matching and known non-matching
      image pairs. Another test on 95 cartridge cases from a different set of slides
      manufactured by the same process also yielded widely separated distributions. The
      test results were used to develop two statistical models for the probability mass
      function of CMC correlation scores. The models were applied to develop a
      framework for estimating cumulative false positive and false negative error rates
      and individual error rates of declared matches and non-matches for this
      population of breech face impressions. The prospect for applying the models to
      large populations and realistic case work is also discussed. The CMC method can
      provide a statistical foundation for estimating error rates in firearm evidence
      identifications, thus emulating methods used for forensic identification of DNA
      evidence.

PMID- 29331682
TI  - Post mortem tryptase cut-off level for anaphylactic death.
AB  - Serum mast cell tryptase is used to support the diagnosis of anaphylaxis. The
      recommended clinical cut-off for total tryptase (<11.4MUg/L) appears unsuitable
      in the post mortem setting due to largely unknown processes which result in
      significantly elevated levels in these samples. Consequently there is no widely
      accepted tryptase cut-off level for diagnosing an anaphylactic death. This 5-year
      retrospective study compared total tryptase levels in post mortem femoral blood
      in anaphylactic deaths and control. Univariate and multivariate analysis was used
      to assess the relative contribution of other factors (age, gender, post mortem
      interval, and presence of resuscitation) on post mortem tryptase levels. Nine
      anaphylactic deaths and 45 controls were identified. Receiver-operating
      characteristic (ROC) curve analysis identified an optimal cut-off of 53.8MUg/L,
      with sensitivity of 89%, and specificity of 93%, for total post mortem tryptase
      in femoral blood to diagnosis anaphylaxis. No other factors showed any
      statistical significant contribution to post mortem tryptase elevation. Femoral
      total post mortem tryptase level of 53.8MUg/L and above is a useful ancillary
      test in diagnosing an anaphylactic death.

PMID- 29331683
TI  - Appropriate fossil calibrations and tree constraints uphold the Mesozoic
      divergence of solenodons from other extant mammals.
AB  - The mammalian order Eulipotyphla includes four extant families of insectivorans:
      Solenodontidae (solenodons); Talpidae (moles); Soricidae (shrews); and
      Erinaceidae (hedgehogs). Of these, Solenodontidae includes only two extant
      species, which are endemic to the largest islands of the Greater Antilles: Cuba
      and Hispaniola. Most molecular studies suggest that eulipotyphlan families
      diverged from each other across several million years, with the basal split
      between Solenodontidae and other families occurring in the Late Cretaceous. By
      contrast, Sato et al. (2016) suggest that eulipotyphlan families diverged from
      each other in a polytomy ~58.6 million years ago (Mya). This more recent
      divergence estimate for Solenodontidae versus other extant eulipotyphlans
      suggests that solenodons must have arrived in the Greater Antilles via overwater
      dispersal rather than vicariance. Here, we show that the young timetree estimates
      for eulipotyphlan families and the polytomy are due to an inverted ingroup
      outgroup arrangement of the tree, the result of using Tracer rather than
      TreeAnnotator to compile interfamilial divergence times, and of not enforcing the
      monophly of well-established clades such as Laurasiatheria and Eulipotyphla.
      Finally, Sato et al.'s (2016) timetree includes several zombie lineages where
      estimated divergence times are much younger than minimum ages that are implied by
      the fossil record. We reanalyzed Sato et al.'s (2016) original data with enforced
      monophyly for well-established clades and updated fossil calibrations that
      eliminate the inference of zombie lineages. Our resulting timetrees, which were
      compiled with TreeAnnotator rather than Tracer, produce dates that are in good
      agreement with other recent studies and place the basal split between
      Solenodontidae and other eulipotyphlans in the Late Cretaceous.

PMID- 29331684
TI  - Reprogramming neurodegeneration in the big data era.
AB  - Recent genome-wide association studies (GWAS) have identified numerous genetic
      risk variants for late-onset Alzheimer's disease (AD) and Parkinson's disease
      (PD). However, deciphering the functional consequences of GWAS data is
      challenging due to a lack of reliable model systems to study the genetic variants
      that are often of low penetrance and non-coding identities. Pluripotent stem cell
      (PSC) technologies offer unprecedented opportunities for molecular phenotyping of
      GWAS variants in human neurons and microglia. Moreover, rapid technological
      advances in whole-genome RNA-sequencing and epigenome mapping fuel comprehensive
      and unbiased investigations of molecular alterations in PSC-derived disease
      models. Here, we review and discuss how integrated studies that utilize PSC
      technologies and genome-wide approaches may bring new mechanistic insight into
      the pathogenesis of AD and PD.

PMID- 29331685
TI  - Nucleic adaptability of heterokaryons to fungicides in a multinucleate fungus,
      Sclerotinia homoeocarpa.
AB  - Sclerotinia homoeocarpa is the causal organism of dollar spot in turfgrasses and
      is a multinucleate fungus with a history of resistance to multiple fungicide
      classes. Heterokaryosis gives rise to the coexistence of genetically distinct
      nuclei within a cell, which contributes to genotypic and phenotypic plasticity in
      multinucleate fungi. We demonstrate that field isolates, resistant to either a
      demethylation inhibitor or methyl benzimidazole carbamate fungicide, can form
      heterokaryons with resistance to each fungicide and adaptability to serial
      combinations of different fungicide concentrations. Field isolates and putative
      heterokaryons were assayed on fungicide-amended media for in vitro sensitivity.
      Shifts in fungicide sensitivity and microsatellite genotypes indicated that
      heterokaryons could adapt to changes in fungicide pressure. Presence of both
      nuclei in heterokaryons was confirmed by detection of a single nucleotide
      polymorphism in the beta-tubulin gene, the presence of microsatellite alleles of
      both field isolates, and the live-cell imaging of two different fluorescently
      tagged nuclei using laser scanning confocal microscopy. Nucleic adaptability of
      heterokaryons to fungicides was strongly supported by the visualization of
      changes in fluorescently labeled nuclei to fungicide pressure. Results from this
      study suggest that heterokaryosis is a mechanism by which the pathogen adapts to
      multiple fungicide pressures in the field.

PMID- 29331686
TI  - Quercetin decrease somatic cells count in mastitis of dairy cows.
AB  - Quercetin is a dietary flavonoid which has an effect on inflammation,
      angiogenesis and vascular inflammation. In several other flavonoids (e.g.
      kaempferol, astragalin, alpinetin, baicalein, indirubin), anti-inflammatory
      mechanism was proven by using mice mastitis model. The aim of the current study
      was pilot analysis of quercetin tolerability and its impact on somatic cells
      count (SCC) after multiple intramammary treatment on dairy cows with clinical
      mastitis. Based on SCC and clinical investigation, 9 dairy cows with clinical
      mastitis of one quarter were selected for the pilot study. Baseline analysis
      (hematology, TNFalpha, SCC) was performed every 24h among all cows three days
      before the first dose (B1-B3). After the baseline monitoring (B1-B3) eight days
      treatment (D1-D8) was performed with a high and low dose. Selected blood
      parameters were analyzed. Starting from D1 to D8, a decrease of SCC in relation
      to baseline was characterized by declining trend. The presented results allowed
      the confirmation of the significant influence of quercetin on the reduction of
      SCC in mastitis in dairy cows after 8days of therapy.

PMID- 29331687
TI  - Probiotics Bacillus toyonensis and Saccharomyces boulardii improve the vaccine
      immune response to Bovine herpesvirus type 5 in sheep.
AB  - There have been significant efforts toward the development of more efficient
      vaccines for animal health. A strategy that may be used to improve vaccine
      efficacy is the use of probiotics. Bovine herpesvirus 5 (BoHV-5) is an example of
      an important animal pathogen for which vaccines have provided only limited
      protection. In this study, we examined the use of the probiotics Bacillus
      toyonensis and Saccharomyces boulardii as a potential immune modulator to improve
      vaccine efficiency. Thirty, 5-month-old lambs were randomly grouped in three lots
      of 10 each and vaccinated at days 0, 21 and 42 of the experiment. They grazed on
      the same pasture and were fed ad libitum twice a day with commercial sheep feed
      supplemented with either B. toyonensis (1*106CFU/g of feed) or S. boulardii
      (1*107CFU/g of feed), or non-supplemented feed. The probiotic supplementation was
      suspended day 28; thereafter, the next 35days, they were fed with the same
      commercial feed as control group. Animals supplemented with probiotics showed a
      significant (p>0.001) increased seroconversions against BoHV-5, and higher
      neutralizing antibodies titres (p>0.05) to BoHV-5 than non-supplemented animals.
      At 63days of experiment, splenocytes from the supplemented sheep had higher mRNA
      transcription levels of cytokines IL-10 and IL-17A. These results suggest that
      these probiotics could provide a promising means of improving vaccine efficacy.

PMID- 29331688
TI  - Coproheme decarboxylases - Phylogenetic prediction versus biochemical
      experiments.
AB  - Coproheme decarboxylases (ChdCs) are enzymes responsible for the catalysis of the
      terminal step in the coproporphyrin-dependent heme biosynthesis pathway.
      Phylogenetic analyses confirm that the gene encoding for ChdCs is widespread
      throughout the bacterial world. It is found in monoderm bacteria (Firmicutes,
      Actinobacteria), diderm bacteria (e. g. Nitrospirae) and also in Archaea. In
      order to test phylogenetic prediction ChdC representatives from all clades were
      expressed and examined for their coproheme decarboxylase activity. Based on
      available biochemical data and phylogenetic analyses a sequence motif (-Y-P-M/F-X
      K/R-) is defined for ChdCs. We show for the first time that in diderm bacteria an
      active coproheme decarboxylase is present and that the archaeal ChdC homolog from
      Sulfolobus solfataricus is inactive and its physiological role remains elusive.
      This shows the limitation of phylogenetic prediction of an enzymatic activity,
      since the identified sequence motif is equally conserved across all previously
      defined clades.

PMID- 29331689
TI  - Baicalin inhibits pressure overload-induced cardiac fibrosis through regulating
      AMPK/TGF-beta/Smads signaling pathway.
AB  - AMP-activated protein kinase (AMPK) is a central regulator of multiple metabolic
      pathways. It has been shown that activation of AMPK could inhibit fibroblast
      proliferation and extracellular matrix (ECM) accumulation, thereby suppressing
      cardiac fibrosis. Baicalin, the major component found in skullcap, possesses
      multiple protective effects on the cardiovascular system. However, little is
      known about the effect of baicalin on cardiac fibrosis and the molecular
      mechanism by which baicalin exerts its anti-fibrotic effects has not been
      investigated. In this study, we revealed that baicalin could inhibit cell
      proliferation, collagen synthesis, fibronectin (FN) and Connective tissue growth
      factor (CTGF) protein expression in cardiac fibroblasts induced by angiotensin II
      (Ang II). It also ameliorated cardiac fibrosis in rats submitted to abdominal
      aortic constriction (AAC). Moreover, baicalin inhibited transforming growth
      factor-beta (TGF-beta)/Smads signaling pathway stimulated with Ang II through
      activating AMPK. Subsequently, we also demonstrated that baicalin attenuated Ang
      II-induced Smad3 nuclear translocation, and interaction with transcriptional
      coactivator p300, but promoted the interaction of p300 and AMPK. Taken together,
      these results provide the first evidence that the effect of baicalin against
      cardiac fibrosis may be attributed to its regulation on AMPK/TGF-beta/Smads
      signaling, suggesting the therapeutic potential of baicalin on the prevention of
      cardiac fibrosis and heart failure.

PMID- 29331690
TI  - Effect of depressive symptoms on the evolution of neuropsychological functions
      over the course of adolescence.
AB  - INTRODUCTION: Comprehensive understanding of the association between depression
      and neuropsychological functioning over the course of adolescence requires
      developmentally sensitive assessment through longitudinal data. The aim of
      current study is to examine the concurrent and subsequent effects of depressive
      symptoms on the initial level and evolution of four neuropsychological
      functioning domains (i.e., spatial working memory, delayed recall memory,
      perceptual reasoning, and inhibitory control). METHOD: Depressive symptoms and
      neuropsychological functioning were assessed over the course of four years in a
      sample of 3826 Canadian adolescents. A series of multilevel models estimated the
      between-person, within-person, and lagged within-person effects of depressive
      symptoms on each domain of neuropsychological functioning. RESULTS: Findings
      suggest that current year and past year depressive symptoms were associated with
      poorer performance in delayed recall memory and perceptual reasoning tasks.
      Likewise, past year depressive symptoms were associated with poorer spatial
      working memory performance. These detrimental effects were stronger in early
      adolescence. LIMITATIONS: The current study examined the presence of sub-clinical
      depressive symptoms but not clinical depression. Moreover, although depressive
      symptoms and neuropsychological functions were assessed using widely used, valid,
      and reliable computer-based instruments, the results may not match the accuracy
      of clinician-based assessments. CONCLUSIONS: Our results underline the necessity
      of early intervention for young adolescents to decrease the harms associated with
      depression. The effect of early-onset depression on the underlying neural
      substrates of neuropsychological functioning merits further investigation.

PMID- 29331691
TI  - Design limitations to bipolar II treatment efficacy studies: A challenge and a
      revisionist strategy.
AB  - BACKGROUND: Trials examining medication efficacy for bipolar II disorder commonly
      employ a set of standardized interval measures to assess outcomes. The key issue
      is whether such interval measures pick up changes in the severity, duration and
      frequency of depressive, hypomanic and euthymic episodes. METHOD: We examine the
      application of measures most commonly used to monitor progress in nine studies
      involving participants with a bipolar II disorder and published in journals with
      a moderate to high impact factor. RESULTS: Studies rarely provided interval
      details for assessing depressive and hypomanic symptoms. None specified whether
      ratings of depressive and hypomanic symptoms were based on severity, duration or
      number of symptoms, and none recorded any data on euthymic periods. LIMITATIONS:
      Our sample of reviewed studies was small and our analyses focused only on the
      three most commonly used outcome measures. We advocate for complementary
      subjective daily mood monitoring strategies but recognize that such strategies
      need to be validated in future studies. CONCLUSIONS: We argue that interval
      ratings undertaken weekly or over longer periods may compromise efficacy data. We
      recommend that userguides be developed to ensure standard outcome measures are
      employed consistently across trials, and that specific details be published in
      trial papers about how measures were employed and what mood episode
      characteristics were measured at each assessment. We also argue for daily ratings
      to be used as an outcome measure to provide data on severity, frequency and
      duration of depressive, hypomanic and euthymic periods in intervention studies of
      those with a bipolar II disorder.

PMID- 29331693
TI  - Disease management apps and technical assistance systems for bipolar disorder:
      Investigating the patients' point of view.
AB  - BACKGROUND: Smartphone-based disease management has become increasingly
      interesting for research in the field of bipolar disorders. This article
      investigates the attitudes of persons affected by this disorder towards the
      appropriation of mobile apps or assistance systems for the management of their
      disease. METHODS: We conducted two separate studies. Study 1 was an online survey
      with 88 participants. In study 2 we consulted 15 participants during a semi
      structured interview. All the participants had formerly been diagnosed with
      bipolar disorder. RESULTS: More than half of the participants of study 1 and most
      participants of study 2 agreed with the use of an app or assistance system for
      self-ratings, third party ratings and an objective symptom monitoring. Potential
      interventions that were popular in both groups included a regular feedback, the
      visualization of monitored data and advice in crises. LIMITATIONS: With study 1
      we were not able to ensure correct diagnoses or to interact in a flexible way. In
      Study 2 those issues were resolved, but the small number of participants raises
      the question of a possible generalisability of the results. Furthermore, for both
      studies a selection bias could not be excluded. CONCLUSIONS: Our results indicate
      positive attitudes of bipolar patients towards disease management apps and
      assistance systems. Even new and innovative features such as partner apps or the
      analysis of facial expressions in video data were appreciated and daily
      interactions were favoured. However, the variety of answers calls for flexible
      systems which allow activating or deactivating certain features.

PMID- 29331692
TI  - Memory performance predicts response to psychotherapy for depression in bipolar
      disorder: A pilot randomized controlled trial with exploratory functional
      magnetic resonance imaging.
AB  - OBJECTIVE: This pilot randomized controlled trial compared Cognitive Behavior
      Therapy (CBT) and Supportive Psychotherapy (SP) for the treatment of depression
      in bipolar I disorder. We also examined whether exploratory verbal memory,
      executive functioning, and neural correlates of verbal memory during functional
      magnetic resonance imaging (fMRI) predicted change in depression severity.
      METHODS: Thirty-two adults (ages 18-65) with DSM-IV bipolar I disorder meeting
      current criteria for a major depressive episode were randomized to 18 weeks of
      CBT or SP. Symptom severity was assessed before, at the mid-point, and after the
      18-week intervention. All participants completed a brief pre-treatment
      neuropsychological testing battery (including the California Verbal Learning Test
      2nd Edition, Delis Kaplan Executive Functioning System [DKEFS] Trail-making Test,
      and DKEFS Sorting Test), and a sub-set of 17 participants provided usable fMRI
      data while completing a verbal learning paradigm that consisted of encoding word
      lists. RESULTS: CBT and SP yielded comparable improvement in depressive symptoms
      from pre- to post-treatment. Better retention of learned information (CVLT-II
      long delay free recall vs. Trial 5) and recognition (CVLT-II hits) were
      associated with greater improvement in depression in both treatments. Increased
      activation in the left dorsolateral prefrontal cortex and right hippocampus
      during encoding was also related to depressive symptom improvement. LIMITATIONS:
      Sample size precluded tests of clinical factors that may interact with
      cognitive/neural function to predict treatment outcome. CONCLUSION:
      Neuropsychological assessment and fMRI offer additive information regarding who
      is most likely to benefit from psychotherapy for bipolar depression.

PMID- 29331694
TI  - Distinctive use of newer and older antidepressants in major geographical areas: A
      nationally representative register-based study.
AB  - BACKGROUND: It is unknown whether newer, mainly selective serotonin reuptake
      inhibitors, and older tricyclic antidepressants are used similarly regardless of
      the geographical area of residence and education. METHODS: We included four
      randomly sampled cohorts of the Finnish working aged population (n = 998,540
      1,033,135). The sampling (Dec 31st in 1995, 2000, 2004 and 2010) resulted in non
      overlapping time windows where each participant was followed up for four years
      for the first antidepressant use. Using Cox proportional hazards models, we
      examined whether the hazard of antidepressant use differed between the capital
      area and three other areas (Southern, Western and Northern/Eastern Finland).
      Educational differences were examined using four sub-groups: capital area/high
      education (reference category); other areas/high education; capital area/low
      education; and other areas/low education. RESULTS: Hazard ratios for the use of
      newer antidepressants were significantly lower in all other areas compared to the
      capital area after adjustment for age, sex, marital status, employment status,
      education, income, and area-level unemployment. Findings remained consistent in
      all time windows, differences increasing slightly. In the sub-group analysis
      those with low education had the lowest level of use in all areas, also within
      the capital area. The results were opposite for older antidepressants in all but
      the last time window. LIMITATIONS: Some degree of unmeasured confounding and
      exposure misclassification is likely to exist. CONCLUSIONS: Newer antidepressants
      were more commonly used in the capital than in the other areas, and among those
      with high versus low education. These differences in antidepressant use suggest
      socioeconomic inequalities in the mental health treatment quality.

PMID- 29331695
TI  - Depression and playfulness in fathers and young infants: A matched design
      comparison study.
AB  - BACKGROUND: Depression in fathers in the postnatal period is associated with an
      increased risk of some adverse child developmental outcomes. One possible
      mechanism for the familial transmission of risk is through the negative effects
      of depression on parenting and the parent-child relationship. So far, evidence
      indicates that depressed fathers tend to be more withdrawn in their early
      interactions. However, the interaction dimensions studied to date may not be able
      to detect and accurately classify unique features of father-infant play -
      including physically stimulating and highly rousing episodes of play. Hence, in
      this matched design comparison study, we set out to examine, for the first time,
      links between diagnosed paternal depression in the postnatal period and
      playfulness in father-infant interactions. METHODS: Fathers and their infants
      were assessed when the infants were 3 months old. Paternal depression was
      diagnosed using a structured psychiatric interview. Currently depressed (n = 19)
      and non-depressed (n = 19) fathers were individually matched on age and
      education. Fathers were filmed playing with their children. Four dimensions were
      coded for paternal playfulness during free-play: physicality, playful excitation,
      tactile stimulation and active engagement. RESULTS: Depressed fathers, compared
      to non-depressed fathers, engaged in fewer episodes of playful excitation (mean
      scores: 0.71 vs.2.53, p = 0.005), less gentle touch (mean time: 38.57 vs. 53.37,
      p = 0.015) and less active engagement (mean scores: 2.29 vs 3.24, p = 0.044).
      When controlling for infant fretfulness, the findings remained largely unchanged.
      LIMITATIONS: The sample size was small and the sample was limited to mostly
      white, well-educated fathers. CONCLUSIONS: Playful paternal behaviours as early
      as 3 months differ between fathers with and without depression. These changes may
      help in understanding children's risk in relation to paternal psychopathology and
      could be a target for future family interventions.

PMID- 29331696
TI  - Does early response predict subsequent remission in bipolar depression treated
      with repeated sleep deprivation combined with light therapy and lithium?
AB  - BACKGROUND: The combination of three cycles of sleep deprivation (SD), light
      therapy (LT), and lithium has recently been proposed as a possible first-line
      treatment for bipolar depression. However, it is unclear whether early
      improvement predicts final response/remission in bipolar depression treated with
      this regimen. METHOD: We studied 220 consecutively admitted inpatients with a
      major depressive episode in the course of bipolar disorder. The relation between
      response to first SD and response/remission at the end of the treatment (day 6)
      was analyzed using logistic regression analysis. Severity of depression was rated
      using the Hamilton Depression Rating Scale (HDRS). Clinical response was defined
      as a >=50% reduction in HDRS scores, and remission was defined as an HDRS score
      of <=7. RESULTS: Among the 217 completers, 67.7% showed response and 54.4%
      reached remission at the end of the treatment. Multiple logistic regression
      analysis revealed that response after first recovery sleep (day 2) predicted
      final response and remission at the end of the treatment with high odds ratios
      (10.9 for response and 8.2 for remission); however, response immediately after
      the first SD (day 1) did not predict final response or remission. LIMITATIONS:
      Whether our results can be generalized to unipolar depression remains uncertain.
      CONCLUSION: Clinical status after first recovery sleep is a strong predictor of
      successful final outcome in patients with bipolar depression treated with the
      combination of repeated SD, LT, and lithium. Recovery sleep may play a role in
      inducing the antidepressant effect associated with the success of treatment.

PMID- 29331697
TI  - Longitudinal trajectories of post-traumatic stress disorder (PTSD) after birth
      and associated risk factors.
AB  - BACKGROUND: Although longitudinal trajectories of post-traumatic stress disorder
      (PTSD) are well-established in general trauma populations, very little is known
      about the trajectories of birth-related PTSD. This study aimed to identify
      trajectories of birth-related PTSD; determine factors associated with each
      trajectory; and identify women more likely to develop birth-related PTSD. METHOD:
      226 women who had traumatic childbirth according to DSM-IV criterion A were drawn
      from a community sample of 950 women. Measures were taken of PTSD, affective
      symptoms, fear of childbirth and social support in pregnancy, 4-6 weeks and 6
      months postpartum. Information on some obstetric and psychosocial factors were
      also prospectively obtained. RESULTS: Four trajectories were identified:
      resilience (61.9%), recovery (18.5%), chronic-PTSD (13.7%) and delayed-PTSD
      (5.8%). Resilience was consistently distinguished from other PTSD trajectories by
      less affective symptoms at 4-6 weeks postpartum. Poor satisfaction with health
      professionals was associated with chronic-PTSD and delayed-PTSD. When affective
      symptoms at 4-6 weeks postpartum were removed from the model, less social support
      and higher fear of childbirth 4-6 weeks after birth predicted chronic and
      recovery trajectories; whereas experience of further trauma and low levels of
      satisfaction with health professionals were predictive of chronic-PTSD and
      delayed-PTSD, compared to resilience. Additional variables associated with
      different trajectories included antenatal affective symptoms, caesarean-section,
      preterm birth and receiving professional help. LIMITATIONS: Use of self-report
      measures, use of DSM-IV criteria for PTSD diagnosis, and no follow-up beyond six
      months are the main limitations of this study. CONCLUSION: Identified factors may
      inform preventive and treatment interventions for women with traumatic birth
      experiences.

PMID- 29331698
TI  - Exploring metabolic factors and health behaviors in relation to suicide attempts:
      A case-control study.
AB  - BACKGROUND: Suicide attempts are a serious public health concern with devastating
      global impact, thereby necessitating the development of an adequate prevention
      strategy. Few known risk factors of suicide attempts are directly modifiable.
      This study sought to investigate potential associations between health behaviors
      and suicide attempts, identifying novel opportunities for clinicians to help
      prevent suicidal behavior. METHODS: A case-control study was conducted to compare
      body weight, serum total cholesterol, physical activity, tobacco use, and dietary
      food groups among adults who had made a suicide attempt (n = 84) to psychiatric
      inpatients (n = 104) and community controls (n = 93) without history of suicide
      attempt. Multivariable binary logistic regression analyses were used to
      investigate the association between metabolic risk factors and attempted suicide.
      RESULTS: Psychiatric inpatients who had attempted suicide were less likely to be
      physically active [moderate/strenuous (OR 0.42, 95% CI 0.19-0.95) and mild (OR
      0.35, 95% CI 0.16-0.76)] compared to controls. Psychiatric inpatients who
      attempted suicide were more likely to use tobacco (OR 2.25, 95% CI 1.07-4.73)
      compared to controls. Contrary to prior research, obesity, serum total
      cholesterol, and diet were not significantly associated with risk of attempted
      suicide. LIMITATIONS: Our study was limited by its cross-sectional design, which
      precludes the identification of causal or temporal relationships between the risk
      of attempted suicide and factors such as physical activity and tobacco use.
      CONCLUSIONS: Study results suggest that a history of attempted suicide is
      associated with a decreased likelihood of being physically active and an
      increased risk of tobacco use. Further investigation is warranted to understand
      the role of exercise and tobacco use in suicide intervention and prevention
      strategies.

PMID- 29331699
TI  - Simultaneous social causation and social drift: Longitudinal analysis of
      depression and poverty in South Africa.
AB  - BACKGROUND: Two theories have been proposed to explain the observed association
      between depression and poverty, namely social causation and social drift. Little
      is known regarding the relative importance of social causation and social drift
      in low and middle-income countries, where poverty is more severe and where most
      of the world's depressed individuals live. METHODS: We analysed nationally
      representative longitudinal data from the National Income Dynamics Study in South
      Africa and simultaneously tested social causation and social drift hypotheses
      using structural equation modelling across three waves. RESULTS: Worse individual
      economic status at time 1 and 2 was independently associated with worse
      depression two years later at time 2 (standardised linear regression coefficient
      beta = -0.110, Standard Error (SE): 0.024) and four years later at time 3 (beta =
      -0.113, SE: 0.025) respectively. Conversely worse depression at time 1 and time 2
      was independently associated with worse economic status at time 2 (beta = -0.037,
      SE: 0.016) and time 3 (beta = -0.028, SE: 0.012) respectively. In addition, the
      "effect" of depression on future assets was stronger among people with less
      baseline assets. LIMITATIONS: The time span between data rounds is relatively
      short (four years); response rates are unequal across ethnic, age and sex groups;
      and the measure of depression is based on self-report. CONCLUSIONS: Social
      causation and social drift act simultaneously in this population, reinforcing
      poverty/depression cycles. Multi-sectoral policies are required that both prevent
      depression by addressing its economic determinants, and provide evidence-based
      treatment to mitigate the economic impact of depression.

PMID- 29331700
TI  - Effects of macrophage migration inhibitory factor on cardiac reperfusion injury
      in mice with depression induced by constant-darkness.
AB  - RATIONALE: Depression is associated with coronary artery disease and increases
      adverse outcomes and mortality in patients with acute myocardial infarction, but
      the underlying pathophysiological mechanisms remain unclear. OBJECTIVE: To
      evaluate the effect of macrophage migration inhibitory factor (MIF) on cardiac
      ischemia-reperfusion (I/R) injury in mice with constant darkness-induced
      depression. METHODS AND RESULTS: Twenty C57BL/6 mice (8 weeks old, male) were
      randomly divided into 2 groups: one group was housed in a 12h light/dark cycle
      environment (LD) and the other in a constant darkness environment (DD). After 3
      weeks, constant darkness-exposed (DD) mice displayed depression-like behavior as
      indicated by increased immobility in the forced swim test (FST) and lower sucrose
      preference rate. Western blotting revealed cardiac MIF expression was
      significantly lower in the DD mice than that in the LD mice. Next, 84 mice were
      randomly divided into 4 groups: LD sham group, LD I/R group, DD sham group, and
      DD I/R group. Following ischemia and reperfusion, mice in the DD I/R group had a
      larger infarct area and lower heart function index than mice in the LD I/R group
      (P < 0.05 for both). The cardiac pAMPK and pACC expression levels of the DD I/R
      group were also lower in the DD I/R group (P < 0.05). CONCLUSION: DD-induced
      depression might cause decreased expression of MIF in the heart, resulting in
      downregulation of MIF-AMPK signaling and a subsequent adverse outcome after a
      cardiac I/R injury.

PMID- 29331701
TI  - The use of triiodothyronine (T3) in the treatment of bipolar depression: A review
      of the literature.
AB  - BACKGROUND: There is a paucity of treatment options for bipolar depression. The
      use of triiodothyronine (T3) has been suggested as adjunctive treatment. METHODS:
      A search on Medline, Limo and ScienceDirect was performed using the search terms
      bipolar disorder, bipolar depression, treatment resistant, treatment refractory,
      thyroid hormones, triiodothyronine, T3, acceleration and augmentation. RESULTS:
      We retrieved three open studies, one comparative study, two double blind and one
      retrospective chart review. The three open studies observed improvement in
      respectively 56%, 75% and 79% of patients, the retrospective chart review noted
      improvement in 89% of cases and the mirror design showed improvement in 66%. In
      the comparative study T3 performed significantly better than placebo. The only
      randomized double blind study could not prove any substantial difference between
      T3 and placebo. LIMITATIONS: Available studies are scarce and flawed. All have
      (very) low number of subjects: overall, only 353 subjects and only 194 of which
      in prospective trials. In only two of the prospective trials bipolar patients
      were analyzed separately. Comparing the studies is hampered by a high variability
      in assessment tools, baseline medication and degree of treatment-resistance.
      CONCLUSIONS: The few available studies are small and flawed. They do show
      promising results. We found many clues suggesting that T3 could augment and
      accelerate treatment response not only with antidepressants, but also with
      lithium and perhaps with other treatment options, that it might protect against
      rapid cycling bipolar disorder, as well as against relapse during the first few
      years of treatment.

PMID- 29331702
TI  - Is very low infant birth weight a predictor for a five-year course of depression
      in parents? A latent growth curve model.
AB  - BACKGROUND: A very low birth weight (VLBW) is considered as a significant risk
      factor for early-onset developmental problems in infants, but is also discussed
      as a potential risk factor for the development of depressive symptoms in affected
      parents. METHODS: In this study, the 5-year courses of maternal and paternal
      depression with VLBW and term born infants (n = 250 families) are modeled and
      predicted by factors existing at the time of birth. RESULTS: The dyadic
      trajectories of depression could be best described by five classes (I no
      depression, II minor maternal depression, III increasing dyadic depression, IV
      significant maternal depression, V highly depressed mothers). VLBW was a
      significant predictor for the course of parental depression - even under control
      of preexisting psychiatric disorders and other confounders. Interaction effects
      and a dose-response relationship were not existent. LIMITATIONS: Class IV and V
      had to be merged for the prediction analysis, a missing bias could not be ruled
      out, and families with a low birth weight (between 2500 and 1500g) were not
      included. CONCLUSIONS: The results are well in line with what is known from
      studies so far, suggesting that maternal and paternal trajectories of depression
      show distinctable patterns which are associated with a VLBW. An early screening
      of mothers and fathers of a VLBW infant seems reasonable to prevent the
      development of a depression in parents and further difficulties for the child.

PMID- 29331703
TI  - The effects of vortioxetine on cognitive performance in working patients with
      major depressive disorder: A short-term, randomized, double-blind, exploratory
      study.
AB  - BACKGROUND: Major Depressive Disorder (MDD) is a complex disease characterized by
      emotional, physical and cognitive symptoms. We explored the efficacy of
      vortioxetine versus placebo on outcomes of cognition, functioning and mood
      symptoms in working patients with depression, using paroxetine as an active
      reference. METHODS: Gainfully employed patients (18-65 years, N = 152) with MDD
      were randomized 1:1:1 to 8 weeks' double-blind, parallel treatment either with
      vortioxetine (10mg/day) or paroxetine (20mg/day), or with placebo. The primary
      efficacy measure was the Digit Symbol Substitution Test (DSST), analyzed using a
      mixed model for repeated measurements, and the key secondary efficacy measure was
      the University of San Diego Performance-based Skills Assessment - Brief (UPSA-B),
      analyzed using analysis of covariance (last observation carried forward).
      RESULTS: At week 8, DSST and UPSA-B performance had improved relative to baseline
      in all treatment groups, with no statistically significant differences between
      treatment groups. While improvements in mood were comparable for vortioxetine and
      paroxetine, numerical improvements in cognitive performance (DSST) were larger
      with vortioxetine. Vortioxetine significantly improved overall cognitive
      performance and clinician-rated functioning relative to placebo. The majority of
      adverse events were mild or moderate, with nausea being the most common adverse
      event for vortioxetine. LIMITATIONS: Small sample sizes implied limited
      statistical power. CONCLUSION: This explorative study showed no significant
      differences versus placebo in DSST or UPSA-B performance at week 8. However,
      secondary results support vortioxetine as an effective and well-tolerated
      antidepressant, supporting an added benefit for cognition and functioning, which
      could have particular therapeutic relevance for the working patient population.

PMID- 29331704
TI  - Mindfulness-based interventions for major depressive disorder: A comprehensive
      meta-analysis of randomized controlled trials.
AB  - BACKGROUND: This is a meta-analysis of randomized controlled trials (RCTs) of
      mindfulness-based interventions (MBIs) for a current episode of major depressive
      disorder. METHODS: Both English (PubMed, PsycINFO, Embase, and Cochrane Library
      databases) and Chinese (WanFang and CNKI) databases were systematically and
      independently searched. Standardized mean differences (SMDs) and risk ratio (RR)
      +/- their 95% confidence intervals (CIs) based on the random effects model were
      calculated. RESULTS: A total of 11 RCTs with 12 treatment arms (n = 764; MBIs =
      363; and control group = 401) were identified and analyzed. Compared to the
      control group, MDD subjects receiving MBIs showed significant reduction in
      depressive symptoms (n =722; SMD: -0.59, 95% CI: -1.01 to -0.17, I2 = 85%, p =
      0.006) at post-MBIs assessment, but the significance disappeared by the end of
      posttreatment follow-up. Subgroup analyses revealed that positive benefits of
      MBIs was associated with studies that had treatment as usual (TAU) control group,
      Chinese participants, open label design, no gender predominance, subjects younger
      than 44.4 years, and Jadad score >= 3, other illness phase and MBIs as
      augmentation group. CONCLUSION: This meta-analysis found that MBIs was associated
      with reduction of depression severity immediately after MBIs but not at follow up
      endpoint. Further, the positive effects of MBIs were mainly driven by outlying
      studies. Higher quality of RCTs with larger samples and longer study duration are
      needed to confirm the findings.

PMID- 29331705
TI  - Catechol O-methyltransferase (COMT) functional haplotype is associated with
      recurrence of affective symptoms: A prospective birth cohort study.
AB  - BACKGROUND: Catechol-O-methyltransferase (COMT) polymorphisms play an essential
      role in dopamine availability in the brain. However, there has been no study
      investigating whether a functional four-SNP (rs6269-rs4633-rs4818-rs4680)
      haplotype is associated with affective symptoms over the life course. METHODS: We
      tested this using 2093 members of the Medical Research Council National Survey of
      Health and Development (MRC NSHD), who had been followed up since birth in 1946,
      and had data for COMT genotypes, adolescent emotional problems (age 13-15) and at
      least one measure of adult affective symptoms at ages 36, 43, 53, or 60-64 years.
      First, differences in the levels of affective symptoms by the functional
      haplotype using SNPs rs6269, rs4818, and rs4680 were tested in a structural
      equation model framework. Second, interactions between affective symptoms by COMT
      haplotype were tested under an additive model. Finally, a quadratic regressor
      (haplotype2) was used in a curvilinear model, to test for a possible inverted-U
      trend in affective symptoms according to COMT-related dopamine availability.
      RESULTS: Women had a significant interaction between COMT haplotypes and
      adolescent emotional problem on affective symptoms at age 53. Post hoc analysis
      showed a significant positive association between adolescent emotional problems
      and affective symptoms at age 53 years in the middle dopamine availability group
      (valA/valB or met/met; beta = .11, p = .007). For men, no significant
      interactions were observed. CONCLUSIONS: Combination of the COMT functional
      haplotype model and inverted-U model may shed light on the effect of dopaminergic
      regulation on the trajectory of affective symptoms over the life course.

PMID- 29331706
TI  - The association between adherence and outcome in an Internet intervention for
      depression.
AB  - BACKGROUND: Adherence to Internet interventions is often reported to be rather
      low and this might adversely impact the effectiveness of these interventions. We
      investigated if patient characteristics are associated with adherence, and if
      adherence is associated with treatment outcome in a large RCT of an Internet
      intervention for depression, the EVIDENT trial. METHODS: Patients were randomized
      to either care as usual (CAU) or CAU plus the Internet intervention Deprexis. A
      total of 509 participants with mild to moderate depressive symptoms were included
      in the intervention group and of interest for the present study. We assessed
      depression symptoms pre and post intervention (12 weeks). Patient
      characteristics, a self-rating screening for mental disorders, attitudes towards
      online interventions, and quality of life were assessed before randomization.
      RESULTS: Adherence in this study was good with on average seven hours of usage
      time and eight number of sessions spent with the intervention. Some of the
      patient characteristics (age, sex, depressive symptoms, and confidence in the
      effectiveness of the program) predicted higher number of sessions in different
      models (explaining in total between 15 and 25% of variance). Older age (beta =
      .16) and higher depressive symptoms (beta = .15) were associated with higher
      usage duration. Higher adherence to the program predicted a greater symptom
      reduction in depressive symptoms over 12 weeks (number of sessions: beta = .13,
      usage duration: beta = .14), however, this prediction could mostly be explained
      by receiving guidance (beta = .27 and .26). LIMITATIONS: Receiving guidance and
      symptom severity at baseline were confounded since only participants with a
      moderate symptom severity at baseline received e-mail support. Therefore no firm
      conclusions can be drawn from the association we observed between baseline
      symptom severity and usage intensity. CONCLUSIONS: We conclude that older age was
      associated with adherence and adherence was positively associated with outcome.
      The effects we have found were small however suggesting that adherence might also
      be influenced by further variables.

PMID- 29331707
TI  - The mediation effect of PTSD, perceived job stress and resilience on the
      relationship between trauma exposure and the development of depression and
      alcohol use problems in Korean firefighters: A cross-sectional study.
AB  - BACKGROUND: Firefighters constitute a high-risk group for depression and alcohol
      use disorders (AUDs) due to frequent exposure to trauma. Perceived job stress and
      resilience are powerful factors affecting the occurrence of depression and AUDs;
      however, research on this subject is scarce. METHODS: We investigated the
      relationship of perceived job stress and resilience with depression or AUDs in
      firefighters. A total of 7151 Korean firefighters were included for analysis.
      Participants completed self-report scales, including a self-reported number of
      exposure to incident stressors, the Korean Occupational Stress Scale - Short
      Form, the Post-traumatic Stress Disorder (PTSD) Symptoms Checklist - Civilian
      version, the Patient Health Questionnaire 9, the Brief Resilience Scale, and the
      Alcohol Use Disorders Identification Test. Hierarchical multivariable linear
      regression analyses were performed to identify the relationship of perceived job
      stress and resilience with depression or AUDs. Path analyses were applied to
      investigate the mediation effects of PTSD, perceived job stress and resilience
      between trauma exposure and depression or AUDs. RESULTS: There were significant
      associations of perceived job stress and resilience with depression and AUDs,
      respectively, even after adjusting for demographic factors, number of traumatic
      events, and PTSD symptoms. The relationship between trauma exposure and
      depression/AUDs was mediated by PTSD symptoms, which had both direct and indirect
      effects on depression and AUDs; indirect effect was mediated by job stress and
      resilience. CONCLUSIONS: The findings in this study demonstrated that PTSD,
      perceived job stress and resilience can mediate the development of depression or
      AUDs following trauma exposure in firefighters. Efforts to prevent PTSD, reduce
      job stress and increase individual resilience could help prevent depression and
      AUDs. LIMITATIONS: The cross-sectional study design and self-report nature of the
      assessment tools limit the current findings.

PMID- 29331708
TI  - Depression increases subjective stigma of chronic pain.
AB  - BACKGROUND: Individuals suffering from mental as well as physical conditions
      often face stigma, which can adversely affect functioning, treatment seeking, and
      emotional health. We compared levels of stigma experienced by individuals with
      depression and/or chronic pain, to contrast the perception of stigma experienced
      by the sufferers with that of individuals who have never experienced these
      conditions, and to determine whether depression is related to greater experience
      of stigma for chronic pain. METHODS: Four groups of participants (N=236) took
      part in the study: depression only, chronic pain only, comorbid depression and
      chronic pain, and healthy controls. Participants underwent a clinical interview
      and completed a stigma measure that assessed general self-stigma, public stigma,
      treatment stigma, secrecy, and stigmatizing experiences. RESULTS: Healthy
      controls largely underestimated the stigma experienced by individuals with
      depression, but were not inaccurate in estimating stigma experienced by
      individuals with chronic pain. Further, individuals with chronic pain alone
      generally perceived less stigma for their condition than did those with
      depression alone. However, comorbid individuals perceived worse stigma of chronic
      pain compared to individuals with chronic pain alone, suggesting that depression
      may affect the stigma felt by sufferers of conditions other than depression.
      LIMITATIONS: Social desirability may have influenced stigma scores. Comparing
      several groups required adapting a standardized instrument. CONCLUSIONS: Results
      suggest that depression may play a role in the social experience of having a
      health condition, as well as indicate that the general public continues to fail
      to appreciate the negative social pressures experienced by individuals with
      mental health conditions.

PMID- 29331709
TI  - What do the genetic association data say about the high risk of suicide in people
      with depression? A novel network-based approach to find common molecular basis
      for depression and suicidal behavior and related therapeutic targets.
AB  - BACKGROUND: Available sources indicate that the risk of suicide in people with
      major depression is higher than other psychiatric disorders. Although it seems
      that these two conditions may have a shared cause in some cases, no studies have
      been conducted to identify a common basis for them. METHODS: In this study,
      following an extensive review of literature, we found almost all the genes that
      are involved in major depression and suicidal behavior, and we isolated genes
      shared between the two conditions. Then, we found all physical or functional
      interactions within three mentioned gene sets and reconstructed three genetic
      interactive networks. All networks were analyzed topologically and enriched
      functionally. Finally, using a drug repurposing approach, we found the main
      available drugs that interacted with the most central genes shared between
      suicidal behavior and depression. RESULTS: The results demonstrated that BDNF,
      SLC6A4, CREB1, and TNF are the most fundamental shared genes; and generally,
      disordered dopaminergic, serotonergic, and immunologic pathways in neuronal
      projections are the main shared deficient pathways. In addition, we found two
      genes, SLC6A4 and SLC6A2, to be the main therapeutic targets, and Serotonin
      Norepinephrine Reuptake Inhibitors (SNRI) and Tricyclic Antidepressants (TCA) to
      be the most effective drugs for individuals with depression at risk for suicide.
      CONCLUSIONS: Our results, in addition to shedding light on the integrated
      molecular basis of depression-suicide, offer new therapeutic targets for
      individuals with depression at high risk for suicide and could pave the way for
      future preclinical and clinical studies. However, integrative systems biology
      based studies highly depend on existing data and related databases, as well as
      the arrival of new experimental data sources in the future, possibly affecting
      the current results.

PMID- 29331710
TI  - Maternal depression and suicide at immediate prenatal and early postpartum
      periods and psychosocial risk factors.
AB  - Maternal depression has been intensively explored; however, less attention has
      been paid to maternal suicide. No studies to date have observed maternal
      depression and suicide at immediate prenatal and early postpartum stages. In
      total, 213 Chinese women were recruited in hospitals after they were admitted for
      childbirth. All completed a short-term longitudinal survey at perinatal stages.
      Women reported lower depression scores (6.65) and higher suicidal ideation
      incidence (11.74%) after childbirth. Prenatal depression raised the possibility
      of prenatal suicidal ideation, while prenatal depression and suicidal ideation
      increased postpartum depression and suicidal ideation. At immediate prenatal
      stage, marital satisfaction protected women from depression, while miscarriage
      experiences and self-esteem increased the risk. At early postpartum stage, in
      contrast, being first-time mother, marital satisfaction, and harmony with mother
      in-law prevented them from depression. Our study is among the first to confirm
      that women have decreased depression but increased suicidal ideation at early
      postpartum, and a causal relationship between them, which are worthy of public
      attention. Potential protective (marital satisfaction, being first-time mother,
      and harmony with mother-in-law) or risk factors (miscarriage experiences and self
      esteem) of maternal depression and suicidal ideation are identified at perinatal
      stages. This offers reliable guidance for clinical practice of health care.

PMID- 29331711
TI  - Omega-3 supplements reduce self-reported physical aggression in healthy adults.
AB  - There is emerging evidence that Omega-3 polyunsaturated fatty acids (PUFA)
      supplements can decrease aggression. However, experimental studies with adults
      from non-specific populations are scarce. We hypothesized that Omega-3
      supplements would decrease self-reported aggression among non-clinical
      participants. In a double-blind randomized trial, two groups of participants (N =
      194) aged 18-45 from the general population followed a 6-weeks treatment with
      638mg docosahexaenoic acid (DHA) and 772mg eicosapentaenoic acid (EPA) per day or
      the equivalent quantity of copra oil (placebo). Self-reported aggressiveness was
      measured at baseline and after the 6-week treatment period. Findings showed that
      Omega-3 supplements significantly decreased self-reported aggressiveness at the
      end of the 6-week period (d = 0.31). In conclusion, this experiment indicates
      that Omega-3 administration has beneficial effects in reducing aggression among
      the general population.

PMID- 29331712
TI  - Genetic biomarkers for differential diagnosis of major depressive disorder and
      bipolar disorder: A systematic and critical review.
AB  - Depressive symptoms are present in the depressive mood state of bipolar disorder
      (BPD) and major depression disorder (MDD). Often, in clinical practice, BPD
      patients are misdiagnosed with MDD. Therefore, genetic biomarkers could
      contribute to the improvement of differential diagnosis between BPD and MDD. This
      systematic and critical review aimed to find in literature reliable genetic
      biomarkers that may show differences between BPD and MDD. This systematic review
      followed the PRISMA-P method. The terms used to search PubMed, Scopus, PsycINFO,
      and Web of Science were depress*, bipolar, diagnos*, genetic*, biomark*. After
      applying the selection criteria, N = 27 studies were selected, being n = 9 about
      biomarkers for BPD; n = 15, about MDD; and n = 3 for distinguishing MDD from BPD.
      A total of N = 3086 subjects were assessed in the selected studies (n = 486 in
      BPD group; n = 1212 in MDD group; and n = 1388, healthy control group). The
      articles were dated up to June 2017. Of the N = 27 studies, n = 16 assessed gene,
      n = 1 miRNA, n = 2 lcnRNA and n = 3 protein expressions, n = 4 methylation, and n
      = 4 polymorphisms. Some studies applied more than one of these genetic analyses.
      To find reliable genetic biomarkers we have taken into account the methodological
      care during the studies development and their validity. The genetic biomarkers
      selected are related to genes that play a fundamental role in synaptic
      plasticity, neurogenesis, mood control, brain ageing, immune-inflammatory
      processes and mitochondrial respiratory chain. BDNF gene expression was one of
      the genetic biomarkers that highlighted because of its capacity of distinguishing
      BPD and MDD groups, and being adequately reproduced by more than one selected
      study.

PMID- 29331713
TI  - Repeated attempted homicide by administration of drugs documented by hair
      analysis.
AB  - Attempted murder by repeated poisoning is quite rare. The authors describe the
      case of a 62-year-old man who was admitted to an intensive care unit (ICU) for
      neurological disturbances complicated by inhalation pneumopathy. He presented a
      loss of consciousness while his wife was visiting him at the ICU (H0). Forty
      eight hours later (H48), police officers apprehended the patient's wife pouring a
      liquid into his fruit salad at the hospital. Toxicological analyses of a blood
      sample and the infusion equipment (H0), as well as the fruit salad and its
      container (H48), confirmed the attempted poisoning with cyamemazine (H0) and
      hydrochloric acid (H48). In order to evaluate the anteriority of poisonings, hair
      analysis was requested and the medical records of the 6 previous months were also
      examined. Two 6-cm brown hair strands were sampled and the victim's medical
      record was seized in order to determine the treatments he had been given during
      the previous six months. Segmental hair testing on two 6-cm brown hair was
      conducted by GC-MS, LC-DAD and LC-MS/MS (0-2/2-4/4-6 cm; pg/mg). Haloperidol
      (9200/1391/227), amitriptyline (7450/1850/3260), venlafaxine (332/560/260), that
      had never been part of the victim's treatment were detected, as well as some
      benzodiazepines (alprazolam, bromazepam, nordazepam); cyamemazine was also
      detected in all the segments (9960/1610/2367) though only a single dose
      administration was reported in the medical records. The toxicological analyses
      performed at H0 and H48 confirmed the homicide attempts in the ICU. In addition,
      comparison of the results in hair analysis with the medical records confirmed
      repeated poisoning attempts over the previous six months, and thus explain the
      origin of the disorders presented by the victim. This case serves to remind us
      that repeated attempted murder can be difficult to diagnose and that hair
      analysis can be an effective way to detect such attempts.

PMID- 29331714
TI  - Stature estimation formulae for Mexican contemporary population: A sample based
      study of long bones.
AB  - Stature estimation is an important step to create a biological profile for human
      identification of unknown individuals in forensic anthropological practice, and
      it is well known that the long bone length is highly correlated with this
      feature. The purpose of the present study is to develop formulae for height
      estimation, based on simple linear regression model for humerus, femur and tibia
      in Mexican contemporary population. Stature was taken in 56 males and 30 female
      corpses as well as maximum length of three long bones of the limbs after autopsy
      following the Menendez et al. (2014) criteria, at the Facultad de Medicina
      (School of Medicine) of the Universidad Nacional Autonoma de Mexico. Based on
      this data, equations for each sex and for the three long bones were developed,
      obtaining a highly significant (p < .001) linear regression models with
      correlation coefficients of r = 0.820 for female femur and r = 0.855 for male
      tibia. In this manner, the new formulae provide better and reliable results of
      stature estimation for the contemporary population of Mexico.

PMID- 29331715
TI  - Toxicokinetics of Zn and Cd in the earthworm Eisenia andrei exposed to metal
      contaminated soils under different combinations of air temperature and soil
      moisture content.
AB  - This study evaluated how different combinations of air temperature (20  degrees C
      and 25  degrees C) and soil moisture content (50% and 30% of the soil water
      holding capacity, WHC), reflecting realistic climate change scenarios, affect the
      bioaccumulation kinetics of Zn and Cd in the earthworm Eisenia andrei. Earthworms
      were exposed for 21 d to two metal-contaminated soils (uptake phase), followed by
      21 d incubation in non-contaminated soil (elimination phase). Body Zn and Cd
      concentrations were checked in time and metal uptake (k1) and elimination (k2)
      rate constants determined; metal bioaccumulation factor (BAF) was calculated as
      k1/k2. Earthworms showed extremely fast uptake and elimination of Zn, regardless
      of the exposure level. Climate conditions had no major impacts on the
      bioaccumulation kinetics of Zn, although a tendency towards lower k1 and k2
      values was observed at 25  degrees C + 30% WHC. Earthworm Cd concentrations
      gradually increased with time upon exposure to metal-contaminated soils,
      especially at 50% WHC, and remained constant or slowly decreased following
      transfer to non-contaminated soil. Different combinations of air temperature and
      soil moisture content changed the bioaccumulation kinetics of Cd, leading to
      higher k1 and k2 values for earthworms incubated at 25  degrees C + 50% WHC and
      slower Cd kinetics at 25  degrees C + 30% WHC. This resulted in greater BAFs for
      Cd at warmer and drier environments which could imply higher toxicity risks but
      also of transfer of Cd within the food chain under the current global warming
      perspective.

PMID- 29331716
TI  - Bioremediation of cadmium- and zinc-contaminated soil using Rhodobacter
      sphaeroides.
AB  - Bioremediation using microorganisms is a promising technique to remediate soil
      contaminated with heavy metals. In this study, Rhodobacter sphaeroides was used
      to bioremediate soils contaminated with cadmium (Cd) and zinc (Zn). The study
      found that the treatment reduced the overall bioavailable fractions (e.g.,
      exchangeable and carbonate bound phases) of Cd and Zn. More stable fractions
      (e.g., Fe-Mn oxide, organic bound, and residual phases (only for Zn)) increased
      after bioremediation. A wheat seedling experiment revealed that the
      phytoavailability of Cd was reduced after bioremediation using R. sphaeroides.
      After bioremediation, the exchangeable phases of Cd and Zn in soil were reduced
      by as much as 30.7% and 100.0%, respectively; the Cd levels in wheat leaf and
      root were reduced by as much as 62.3% and 47.2%, respectively. However, when the
      soils were contaminated with very high levels of Cd and Zn (Cd 54.97-65.33 mg kg
      1; Zn 813.4-964.8 mg kg-1), bioremediation effects were not clear. The study also
      found that R. sphaeroides bioremediation in soil can enhance the Zn/Cd ratio in
      the harvested wheat leaf and root overall. This indicates potentially favorable
      application in agronomic practice and biofortification. Although remediation
      efficiency in highly contaminated soil was not significant, R. sphaeroides may be
      potentially and practically applied to the bioremediation of soils co
      contaminated by Cd and Zn.

PMID- 29331717
TI  - In vitro dermal bioaccessibility of selected metals in contaminated soil and mine
      tailings and human health risk characterization.
AB  - Dermal exposure to contaminated sites has generally received less attention than
      oral/inhalation exposure due to limited exposure scenarios and less perceived
      potential for toxicity, however, the risk can be significant for specific
      contaminants and scenarios. The present study aims to (1) measure Cr, Ni, Pb, and
      Zn contamination in soil and mine tailings samples (n = 7), (2) determine the
      dermal bioaccessibility of these metals via in vitro tests using two synthetic
      sweat formulations (EN 1811; NIHS 96-10), and (3) obtain dermal absorbed doses
      (DADs) for children's and adults' exposure scenarios and compare them to derived
      dermal reference values. The NIHS 96-10 formulation yielded higher
      bioaccessibility values for all metals than EN 1811, possibly due to its lower
      pH. Zn had the highest bioaccessibility for both formulations whereas Cr had the
      lowest. There was some evidence of adsorption of initially mobilized Pb and Zn to
      soil with longer test times, resulting in slightly lower bioaccessibility after 8
      h of testing with respect to 2 h. The calculated DADs showed that the risk for
      exposure was acceptable (DAD < derived dermal reference value) for all metals
      except for Cr(VI) considering exposure to two of the samples. The risk in the
      case of children's exposure scenario (play on contaminated medium) was
      significantly higher than the case for the adults' exposure scenario (exposure in
      industrial context). Additional bioaccessibility research is recommended on
      additional samples with differing properties/contamination profiles, on
      additional contaminants with high dermal affinity (especially As), and on the
      development/validation of in vitro dermal bioaccessibility tests.

PMID- 29331718
TI  - Partition of Zn, Cd, and Pb during co-combustion of sedum plumbizincicola and
      sewage sludge.
AB  - Co-combustion of sedum plumbizincicola and sewage sludge was performed in a
      tubular furnace. The influence of experimental conditions on the partitioning of
      Zn, Cd, and Pb was investigated. The results showed that 30% sewage sludge was
      proposed as the optimal ratio for the co-combustion as a compromise between low
      calorific value and high amount of heavy metal remained in the bottom ash. High
      temperature increased the volatilization degree of heavy metals, among which the
      performance of Cd and Pb was obvious than Zn. Rising oxygen concentration was
      beneficial to the formation of heavy metal compounds, and the effect of oxygen on
      Zn was the most pronounced. Thermodynamic equilibrium calculation was carried out
      to forecast heavy metal compounds. The results demonstrated that Zn, Cd, and Pb
      mainly generated ZnAl2O4, CdSiO3 and PbSiO3 in solid phase, which are partly
      confirmed by X-ray diffraction (XRD). The promising results offered a great
      possibility of heavy metal immobilization, indicating the combustion of Sedum
      plumbizincicola with sewage sludge is an effective way for waste disposal.

PMID- 29331719
TI  - Regulated effects of Prorocentrum donghaiense Lu exudate on nickel
      bioavailability when cultured with different nitrogen sources.
AB  - Exudates by marine phytoplankton and metals coexist in the seawater, but little
      is known about their interaction. In this study, cultures of Prorocentrum
      donghaiense Lu were grown in urea and ammonium, and then exposed to different Ni
      ion levels in order to study the effects of Ni ions on algal growth. The
      regulatory mechanisms of P. donghaiense Lu for coping with different Ni ion
      levels was investigating by characterizing dissolved organic carbon (DOC),
      carbohydrate and protein content released per cell, hydropathy properties
      (hydrophilic and hydrophobic fractions) and thiol compounds (cysteine-like or
      glutathione-like). Lower levels of Ni ions (pNi>10.0) significantly promoted the
      growth of P. donghaiense Lu when incubated in urea; however, the same was not
      true for P. donghaiense Lu cultivated in ammonium. An increased presence of
      hydrophobic fractions and thiol compounds (cysteine-like or glutathione-like
      compounds) induced by low Ni ions (pNi>10.0) in urea cultures suggest that the
      activation of cellular mechanisms in response to insufficient Ni ion stress
      enhances Ni bioavailability. Furthermore, the abundance of carbohydrates and
      proteins released by cells when exposed to higher Ni ions levels (from pNi = 10.0
      to pNi = 8.0) both in urea and ammonium cultures suggests that algal cells may
      utilize exudate to complex Ni cations and reduce their toxicity. Therefore, it
      can be speculated that phytoplankton can produce large amounts of specific
      exudate, which may accelerate the metal bioavailability (insufficient levels) and
      reduce metal toxicity (excess levels) to maintain an equilibrium with metals in
      the environment.

PMID- 29331720
TI  - Temporal-spatial gait parameter models of very slow walking.
AB  - This study assessed the relationship between walking speed and common temporal
      spatial stride-parameters to determine if a change in gait strategy occurs at
      extremely slow walking speeds. Stride-parameter models that represent slow
      walking can act as a reference for lower extremity exoskeleton and powered
      orthosis controls since these devices typically operate at walking speeds less
      than 0.4 m/s. Full-body motion capture data were collected from 30 health adults
      while walking on a self-paced treadmill, within a CAREN-Extended virtual reality
      environment. Kinematic data were collected for 0.2-0.8 m/s, and self-selected
      walking speed. Eight temporal stride-parameters were determined and their
      relationship to walking speed was assessed using linear and quadratic regression.
      Stride-length, step-length, and step-frequency were linearly related to walking
      speed, even at speeds below 0.4 m/s. An inflection point at 0.5 m/s was found for
      stride-time, step-time, stance-time, and double support time. Equations were
      defined for each stride-parameter, with equation outputs producing correlations
      greater than 0.91 with the test data. This inflection point suggests a change in
      gait strategy at very slow walking speeds favouring greater ground contact time.

PMID- 29331721
TI  - Understanding protein-drug interactions using ion mobility-mass spectrometry.
AB  - Ion mobility-mass spectrometry (IM-MS) is an important addition to the analytical
      toolbox for the structural evaluation of proteins, and is enhancing many areas of
      biophysical analysis. Disease-associated proteins, including enzymes such as
      protein kinases, transcription factors exemplified by p53, and intrinsically
      disordered proteins, including those prone to aggregation, are all amenable to
      structural analysis by IM-MS. In this review we discuss how this powerful
      technique can be used to understand protein conformational dynamics and
      aggregation pathways, and in particular, the effect that small molecules,
      including clinically-relevant drugs, play in these processes. We also present
      examples of how IM-MS can be used as a relatively rapid screening strategy to
      evaluate the mechanisms and conformation-driven aspects of protein:ligand
      interactions.

PMID- 29331722
TI  - Effect of vitamin D supplementation on serum sclerostin levels in chronic kidney
      disease.
AB  - Vitamin D deficiency, cardiovascular disease and abnormal bone mineral metabolism
      are common in chronic kidney disease (CKD). Abnormal bone mineral metabolism has
      been linked to vascular calcification in CKD. Sclerostin has emerged as an
      important messenger in cross talk between bone-vascular axis. We analyzed
      sclerostin in subjects who participated in the randomized, double blind, placebo
      controlled trial investigating the effect of cholecalciferol supplementation on
      vascular function in non-diabetic CKD stage G3-4 and vitamin D <= 20 ng/ml
      [CTRI/2013/05/003648]. Patients were randomized (1:1) to receive either two
      directly observed oral doses of 300,000 IU of cholecalciferol or matching placebo
      at baseline and 8 weeks. Of the 120 subjects enrolled, 58 in the cholecalciferol
      group and 59 in the placebo group completed the study. At baseline, serum levels
      of sclerostin were similar in both groups (cholecalciferol - median;190pg/ml,
      IQR;140-260 pg/ml and placebo - median;180 pg/ml, IQR; 140-240 pg/ml, p = 0.67).
      16 weeks after cholecalciferol supplementation, there was no change in level of
      sclerostin (mean change;1.10 pg/ml, 95%CI; -27.34 to 29.34 pg/ml, p = 0.25).
      However, a significant decrease in sclerostin level was noted in the placebo
      group (mean change; -31.94 pg/ml, 95%CI; -54.76 to -9.13 pg/ml, p = 0.002).
      Change (Delta) in sclerostin level at 16 weeks correlated negatively with Delta
      eGFR (r = -0.20, p = 0.03) and positively with Deltauric acid (r = 0.37, p <
      0.001) but not with Delta25(OH) D (r = 0.06, p = 0.54), Delta iPTH (r = - 0.03, p
      = 0.78) DeltaFGF23 (r = - 0.08, p = 0.38) and Delta125 (OH)2 D (r = - 0.04, p =
      0.65). In conclusion, high dose cholecalciferol supplementation did not change
      sclerostin levels in non-diabetic stage 3-4 CKD subjects.

PMID- 29331723
TI  - Progesterone arrested cell cycle progression through progesterone receptor
      isoform A in pancreatic neuroendocrine neoplasm.
AB  - In pancreatic neuroendocrine neoplasms (Pan-NEN) progesterone signaling has been
      shown to have both inhibitory and stimulatory effects on cell proliferation. The
      ability of progesterone to inhibit tumor proliferation is of particular interest
      and is suggested to be mediated through the less abundantly expressed
      progesterone receptor (PR) isoform A (PRA). To date the mechanistic processes
      underlying this inhibition of proliferation remain unclear. To examine the
      mechanism of PRA actions, the human Pan-NEN cell line QGP-1, that endogenously
      expresses PR isoform B (PRB) without PRA, was transfected with PRA. PRA
      transfection suppressed the majority of cell cycle related genes increased by
      progesterone including cyclin A2 (CCNA2), cyclin B1 (CCNB1), cyclin-dependent
      kinase 1 (CDK1) and cyclin-dependent kinase 2 (CDK2). Importantly, following
      progesterone administration cell cycle distribution was shifted to S and G2/M
      phases in the naive cell line but in PRA-transfected cells, this effect was
      suppressed. To see if these mechanistic insights were confirmed in patient
      samples PRA, PRB, CCNA2, CCNB, CDK1 and CDK2 immunoreactivities were assessed in
      Pan-NEN cases. Higher levels of cell cycle markers were associated with higher
      WHO grade tumors and correlations between the markers suggested formation of
      cyclin/CDK activated complexes in S and G2/M phases. PRA expression was
      associated with inverse correlation of all cell cycle markers. Collectively,
      these results indicate that progesterone signals through PRA negatively regulates
      cell cycle progression through suppressing S and G2/M phases and downregulation
      of cell cycle phases specific cyclins/CDKs.

PMID- 29331724
TI  - Diminution of arsenic accumulation in rice seedlings co-cultured with Anabaena
      sp.: Modulation in the expression of lower silicon transporters, two nitrogen
      dependent genes and lowering of antioxidants activity.
AB  - The present study was intended to investigate the role of algae, Anabaena sp. in
      the amelioration of As toxicity, when co-cultured with rice seedlings. The
      reduction of growth in rice seedlings against As(III) and As(V) was recovered
      with Anabaena sp. The Anabaena sp. also reduced the accumulation of As, where it
      was more efficient against 60uM As(III) (49%) than As(V) (23%) in rice shoot.
      Similarly, with reduction of As accumulation, lower silicon transporters (Lsi-1
      and Lsi-2) was found to be suppressed against As treatments. However, the
      expression of two nitrogen dependent genes i.e., NR and SAMT were found to be
      enhanced with the Anabaena sp. Likewise, the activity of antioxidant enzyme, GST,
      was enhanced, whereas, the activity of other enzymes such as SOD, APX, GPX, GR
      and DHAR were decreased with As+Algae combinations. Overall, the result suggested
      that the Anabaena sp. reduces As accumulation, modulates gene expressions and
      antioxidants to ameliorate the As toxicity in Oryza sativa L.

PMID- 29331725
TI  - BiVO4 /N-rGO nano composites as highly efficient visible active photocatalyst for
      the degradation of dyes and antibiotics in eco system.
AB  - Herein, we report the synthesis of novel nitrogen doped reduced graphene oxide/
      BiVO4 photo catalyst by single step hydrothermal method. The physicochemical
      properties of the catalysts were characterized using XRD, N2 adsorption
      desorption, Raman, XPS, SEM TEM, DRS-UV and EIS techniques. The synthesized
      catalysts were tested for their catalytic activity in the photo degradation of
      some harmful textile dyes (methylene blue & congo red) and antibiotics
      (metronidazole and chloramphenicol) under visible light irradiation. Reduced
      charge recombination and enhanced photocatalytic activity were observed due to
      the concerted effect between BiVO4 and nitrogen-rGO. The degradation efficiency
      of BiVO4/N-rGO in the degradation of CR and MB was remarkably high i.e 95% and
      98% under visible light irradiation. Similarly 95% of MTZ and 93% of CAP were
      degraded under visible light irradiation. HPLC studies implied that both the dyes
      and antibiotics were degraded to the maximum extent. The plausible photocatalytic
      mechanism on the basis of experimental results was suggested.

PMID- 29331726
TI  - Impact of the start-up process on the microbial communities in biocathodes for
      electrosynthesis.
AB  - This study seeks to understand how the bacterial communities that develop on
      biocathodes are influenced by inocula diversity and electrode potential during
      start-up. Two different inocula are used: one from a highly diverse environment
      (river mud) and the other from a low diverse milieu (anaerobic digestion). In
      addition, both inocula were subjected to two different polarising voltages:
      oxidative (+0.2 V vs. Ag/AgCl) and reductive (-0.8 V vs. Ag/AgCl). Bacterial
      communities were analysed by means of high throughput sequencing. Possible
      syntrophic interactions and competitions between archaea and eubacteria were
      described together with a discussion of their potential role in product formation
      and current production. The results confirmed that reductive potentials lead to
      an inconsistent start-up procedure regardless of the inoculum used. However,
      imposing oxidative potentials help to quickly develop an electroactive biofilm
      ready to withstand reductive potentials (i.e. biocathodic operation). The
      microbial structure that finally developed on them was highly dependent on the
      raw community present in the inoculum. Using a non-specialised inoculum resulted
      in a highly specialised biofilm, which was accompanied by an improved performance
      in terms of consumed current and product generation. Interestingly, a much more
      specialised inoculum promoted a rediversification in the biofilm, with a lower
      general cell performance.

PMID- 29331728
TI  - The effect of bioadhesive on the interfacial compatibility and pervaporation
      performance of composite membranes by MD and GCMC simulation.
AB  - Combing molecular dynamics (MD) and Grand Canonical Monte Carlo (GCMC)
      simulation, the effect of bioadhesive transition layer on the interfacial
      compatibility of the pervaporation composite membranes, and the pervaporation
      performance toward penetrant molecules were investigated. In our previous
      experimental study, the structural stability and permeability selectivity of the
      composite membranes were considerably enhanced by the introduction of bioadhesive
      carbopol (CP). In the present study, the interfacial compatibility and the
      interfacial energies between the chitosan (CS) separation layer, CP transition
      layer and the support layer were investigated, respectively. The mobility of
      polymer chains, free volume in bulk and interface regions were evaluated by the
      mean-square displacement (MSD) and free volume voids (FFV) analysis. The
      diffusion and sorption behavior of water/ethanol molecules in bulk and interface
      regions were characterized. The simulation results of membrane structure have
      good consistency, indicating that the introduction of CP transition layer
      improved the interfacial compatibility and interaction between the separation
      layer and the support layer. Comparing the bulk region of the separation layer,
      the mobility and free volume of the polymer chain in the interface region
      decreased and thus reduced the swelling of CS active layer, revealing the
      increased diffusion selectivity toward the permeated water and ethanol molecules.
      The strong hydrogen bonds interaction between the COOH of the CP transition layer
      and water molecules increased the adsorption of water molecules in the interface
      region. The simulation results were quite consistent with the experimental
      results.

PMID- 29331729
TI  - Strong CH/O interactions between polycyclic aromatic hydrocarbons and water:
      Influence of aromatic system size.
AB  - Energies of CH/O interactions between water molecule and polycyclic aromatic
      hydrocarbons with a different number of aromatic rings were calculated using ab
      initio calculations at MP2/cc-PVTZ level. Results show that an additional
      aromatic ring in structure of polycyclic aromatic hydrocarbons significantly
      strengthens CH/O interactions. Calculated interaction energies in optimized
      structures of the most stable tetracene/water complex is -2.27 kcal/mol,
      anthracene/water is -2.13 kcal/mol and naphthalene/water is -1.97 kcal/mol. These
      interactions are stronger than CH/O contacts in benzene/water complex (-1.44
      kcal/mol) while CH/O contacts in tetracene/water complex are even stronger than
      CH/O contacts in pyridine/water complexes (-2.21 kcal/mol). Electrostatic
      potential maps for different polycyclic aromatic hydrocarbons were calculated and
      used to explain trends in the energies of interactions.

PMID- 29331727
TI  - Individual variation in working memory is associated with fear extinction
      performance.
AB  - PTSD has been associated consistently with abnormalities in fear acquisition and
      extinction learning and retention. Fear acquisition refers to learning to
      discriminate between threat and safety cues. Extinction learning reflects the
      formation of a new inhibitory-memory that competes with a previously learned
      threat-related memory. Adjudicating the competition between threat memory and the
      new inhibitory memory during extinction may rely, in part, on cognitive processes
      such as working memory (WM). Despite significant shared neural circuits and
      signaling pathways the relationship between WM, fear acquisition, and extinction
      is poorly understood. Here, we analyzed data from a large sample of healthy
      Marines who underwent an assessment battery including tests of fear acquisition,
      extinction learning, and WM (N-back). Fear potentiated startle (FPS), fear
      expectancy ratings, and self-reported anxiety served as the primary dependent
      variables. High WM ability (N = 192) was associated with greater CS + fear
      inhibition during the late block of extinction and greater US expectancy change
      during extinction learning compared to individuals with low WM ability (N = 204).
      WM ability was not associated with magnitude of fear conditioning/expression.
      Attention ability was unrelated to fear acquisition or extinction supporting
      specificity of WM associations with extinction. These results support the
      conclusion that individual differences in WM may contribute to regulating fear
      responses.

PMID- 29331730
TI  - Exenatide exerts cognitive effects by modulating the BDNF-TrkB neurotrophic axis
      in adult mice.
AB  - Modulation of insulin-dependent signaling is emerging as a valuable therapeutic
      tool to target neurodegeneration. In the brain, the activation of insulin
      receptors promotes cell growth, neuronal repair, and protection. Altered brain
      insulin signaling participates in the cognitive decline seen in Alzheimer's
      disease patients and the aging brain. Glucagon-like peptide-1 (GLP-1) regulates
      insulin secretion and, along with GLP-1 analogues, enhances neurotrophic
      signaling and counteracts cognitive deficits in preclinical models of
      neurodegeneration. Moreover, recent evidence indicates that GLP-1 modulates the
      activity of the brain-derived neurotrophic factor (BDNF). In this study, in adult
      wild-type mice, here employed as a model of mid-life brain aging, we evaluated
      the effects of a 2-month treatment with exenatide, a GLP-1 analogue. We found
      that exenatide promotes the enhancement of long-term memory performances.
      Biochemical and imaging analyses show that the drug promotes the activation of
      the BDNF-TrkB neurotrophic axis and inhibits apoptosis by decreasing p75NTR
      mediated signaling. The study provides preclinical evidence for the use of
      exenatide to delay age-dependent cognitive decline.

PMID- 29331731
TI  - Deoxynivalenol, gut microbiota and immunotoxicity: A potential approach?
AB  - Deoxynivalenol (DON, vomitoxin) is the most frequent mycotoxin in grains and
      grain products. DON contamination in fodder and food is a serious threat for
      health, since it impairs the immune and gastrointestinal systems of both human
      and animals. Gut microbiota seems to play a more and more important part in human
      and animals' health according to related researches. Previous studies implied
      some associations among gut microbiota, DON and immune system. For example, DON
      affects immune system as well as the composition and abundance of gut microbiota,
      and the latter influences immune system as well. In the present short review, we
      not only provide the available information about the toxic consequences of DON
      induced immunotoxicity on different animals and cell lines and discuss its main
      possible molecule mechanisms, but also summarize research results concerning the
      role of gut microbiota in DON-induced immunotoxicity and gender differences, with
      the aim to find some potential therapeutic strategies to tackle DON-induced
      immunotoxicity.

PMID- 29331732
TI  - Computational toxicology: From cheminformatics to nanoinformatics.

PMID- 29331733
TI  - Aronia melanocarpa fruit juice ameliorates the symptoms of inflammatory bowel
      disease in TNBS-induced colitis in rats.
AB  - Trinitrobenzensulfonic acid (TNBS) is commonly used to induce an experimental
      inflammatory bowel disease (IBD) model. Oxidative stress and inflammation have
      been proposed as mechanisms underlying the pathophysiology of IBD. Aronia
      melanocarpa fruit juice (AMFJ) is extremely rich in polyphenolic substances,
      mainly proanthocyanidins, flavonoids and phenolic acids. The aim of this study
      was to evaluate the effect of AMFJ in a rat TNBSinduced colitis model and to
      compare the effect of the juice with that of sulfasalazine. Colitis was induced
      by TNBS in male Wistar rats. After the induction of colitis, AMFJ at three doses
      (2.5, 5 and 10 mL/kg) and sulfasalazine (400 mg/kg) were administered orally till
      the 14th experimental day. Severity of colitis was assessed by macroscopic and
      histopathological criteria. Oxidative stress was evaluated by the concentration
      of thiobarbituric acid reactive substances (TBARS). TNBS caused severe colonic
      damage. AMFJ dose-dependently ameliorated TNBS-induced colitis. It improved the
      macroscopic and microscopic signs of colitis, and prevented the increase of
      colonic TBARS concentrations. Regarding different indices, the effect of AMFJ was
      comparable or even higher than that of sulfasalazine. In conclusion, the
      ameliorative effects of AMFJ in the experimental TNBSinduced colitis might be the
      result of its potent antioxidant and antiinflammatory properties.

PMID- 29331734
TI  - In vitro assessment of silver nanoparticles immunotoxicity.
AB  - This study aimed to characterize unwanted immune effects of nanoparticles (NP)
      using THP-1 cells, human whole blood and enriched peripheral blood monocytes.
      Commercially available silver NP (AgNP < 100 nm, also confirmed by Single
      Particle Extinction and Scattering) were used as prototypical NP. Cells were
      treated with AgNP alone or in combination with classical immune stimuli (i.e.
      LPS, PHA, PWM) and cytokine assessed; in addition, CD54 and CD86 expression was
      evaluated in THP-1 cells. AgNP alone induced dose-related IL-8 production in all
      models, with higher response observed in THP-1 cells, possibly connected to
      different protein corona formation in bovine versus human serum. AgNP potentiated
      LPS-induced IL-8 and TNF-alpha, but not LPS-induced IL-10. AgNP alone induced
      slight increase in IL-4, and no change in IFN-gamma production. While responses
      to PHA in term of IL-4 and IFN-gamma production were not affected, increased PWM
      induced IL-4 and IFN-gamma production were observed, suggesting potentiation of
      humoral response. Reduction in PHA-induced IL-10 was observed. Overall, results
      indicate immunostimulatory effects. THP-1 cells work as well as primary cells,
      representing a useful and practical alternative, with the awareness that from a
      physiological point of view the whole blood assay is the one that comes closest
      to reality.

PMID- 29331735
TI  - Internal exposure-based pharmacokinetic evaluation of potential for
      biopersistence of 6:2 fluorotelomer alcohol (FTOH) and its metabolites.
AB  - Polyfluorinated compounds (PFCs) are authorized for use as greaseproofing agents
      in food contact paper. As C8-PFCs (8-carbons) are known to accumulate in tissues,
      shorter-chain C6-PFCs (6-carbons) have replaced C8-PFCs in many food contact
      applications. However, the potential of C6-PFCs for human biopersistence has not
      been fully evaluated. For the first time, we provide internal exposure estimates
      to key metabolites of 6:2 fluorotelomer alcohol (6:2 FTOH), a monomeric component
      of C6-PFCs, to extend our understanding of exposure beyond estimates of external
      exposure. Pharmacokinetic data from published rat and human studies on 6:2 FTOH
      were used to estimate clearance and area under the curve (AUC) for its
      metabolites: 5:3 fluorotelomer carboxylic acid (5:3 A), perfluorohexanoic acid
      (PFHxA) and perfluoroheptanoic acid (PFHpA). Internal exposure to 5:3 A was the
      highest of evaluated metabolites across species and it had the slowest clearance.
      Additionally, 5:3 A clearance decreased with increasing 6:2 FTOH exposure. Our
      analysis provides insight into association of increased internal 5:3 A exposure
      with high biopersistence potential of 6:2 FTOH. Our results identify 5:3 A as an
      important biomarker of internal 6:2 FTOH exposure for use in biomonitoring
      studies, and are potentially useful for toxicological assessment of chronic
      dietary 6:2 FTOH exposure.

PMID- 29331737
TI  - Hematology reference intervals for neonatal Holstein calves.
AB  - Data regarding hematologic reference intervals (RI) for neonatal calves have not
      been published yet. The aims of this study were: a) to establish hematology RIs
      for neonatal Holstein calves, b) to compare them with the RIs for lactating cows,
      and c) to investigate the relationship of age and gender with the hematologic
      profile of calves. Two-hundred and fifty-four clinically healthy Holstein calves
      (1-9days old, from 30 farms) and 82 healthy Holstein cows (between 30 and 150days
      in milk, from 10 farms) were blood sampled once for a complete blood count
      evaluation, using the ADVIA 120 hematology analyzer. An additional blood sample
      was collected from each calf for serum total protein concentration measurement.
      RIs and age-related RIs were calculated with the Reference Value Advisor
      freeware. Comparisons between calves and cows and between male and female calves
      were performed with t-test or Mann-Whitney test. Red blood cell count (RBC),
      white blood cell count (WBC), neutrophil, lymphocyte and platelet counts in
      calves were higher, while mean corpuscular volume (MCV), mean corpuscular
      hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) were lower
      than in cows. Lymphocyte and platelets showed a notable increase through age.
      Finally, female calves had higher RBC, hematocrit and hemoglobin concentration
      than males. Age-specific RIs should be used for the interpretation of the
      complete blood count in Holstein calves.

PMID- 29331738
TI  - Recent advances in neural dust: towards a neural interface platform.
AB  - The neural dust platform uses ultrasonic power and communication to enable a
      scalable, wireless, and batteryless system for interfacing with the nervous
      system. Ultrasound offers several advantages over alternative wireless
      approaches, including a safe method for powering and communicating with sub mm
      sized devices implanted deep in tissue. Early studies demonstrated that neural
      dust motes could wirelessly transmit high-fidelity electrophysiological data in
      vivo, and that theoretically, this system could be miniaturized well below the mm
      scale. Future developments are focused on further minimization of the platform,
      better encapsulation methods as a path towards truly chronic neural interfaces,
      improved delivery mechanisms, stimulation capabilities, and finally refinements
      to enable deployment of neural dust in the central nervous system.

PMID- 29331739
TI  - Determination of atomic-scale chemical composition at semiconductor
      heteroepitaxial interfaces by high-resolution transmission electron microscopy.
AB  - The determination of atomic structures and further quantitative information such
      as chemical compositions at atomic scale for semiconductor defects or
      heteroepitaxial interfaces can provide direct evidence to understand their
      formation, modification, and/or effects on the properties of semiconductor films.
      The commonly used method, high-resolution transmission electron microscopy
      (HRTEM), suffers from difficulty in acquiring images that correctly show the
      crystal structure at atomic resolution, because of the limitation in microscope
      resolution or deviation from the Scherzer-defocus conditions. In this study, an
      image processing method, image deconvolution, was used to achieve atomic
      resolution (~1.0 A) structure images of small lattice-mismatch (~1.0%) AlN/6H-SiC
      (0001) and large lattice-mismatch (~8.5%) AlSb/GaAs (001) heteroepitaxial
      interfaces using simulated HRTEM images of a conventional 300-kV field-emission
      gun transmission electron microscope under non-Scherzer-defocus conditions. Then,
      atomic-scale chemical compositions at the interface were determined for the
      atomic intermixing and Lomer dislocation with an atomic step by analyzing the
      deconvoluted image contrast. Furthermore, the effect of dynamical scattering on
      contrast analysis was also evaluated for differently weighted atomic columns in
      the compositions.

PMID- 29331736
TI  - Dysfunctional telomeres and hematological disorders.
AB  - Telomere biology disorders, which are characterized by telomerase activity
      haploinsufficiency and accelerated telomere shortening, most commonly manifest as
      degenerative diseases. Tissues with high rates of cell turnover, such as those in
      the hematopoietic system, are particularly vulnerable to defects in telomere
      maintenance genes that eventually culminate in bone marrow (BM) failure
      syndromes, in which the BM cannot produce sufficient new blood cells. Here, we
      review how telomere defects induce degenerative phenotypes across multiple
      organs, with particular focus on how they impact the hematopoietic stem and
      progenitor compartment and affect hematopoietic stem cell (HSC) self-renewal and
      differentiation. We also discuss how both the increased risk of myelodysplastic
      syndromes and other hematological malignancies that is associated with telomere
      disorders and the discovery of cancer-associated somatic mutations in the
      shelterin components challenge the conventional interpretation that telomere
      defects are cancer-protective rather than cancer-promoting.

PMID- 29331740
TI  - Development and validation of a new population-based simulation model of
      osteoarthritis in New Zealand.
AB  - OBJECTIVE: To describe the construction and preliminary validation of a new
      population-based microsimulation model developed to analyse the health and
      economic burden and cost-effectiveness of treatments for knee osteoarthritis (OA)
      in New Zealand (NZ). METHOD: We developed the New Zealand Management of
      Osteoarthritis (NZ-MOA) model, a discrete-time state-transition microsimulation
      model of the natural history of radiographic knee OA. In this article, we report
      on the model structure, derivation of input data, validation of baseline model
      parameters against external data sources, and validation of model outputs by
      comparison of the predicted population health loss with previous estimates.
      RESULTS: The NZ-MOA model simulates both the structural progression of
      radiographic knee OA and the stochastic development of multiple disease symptoms.
      Input parameters were sourced from NZ population-based data where possible, and
      from international sources where NZ-specific data were not available. The
      predicted distributions of structural OA severity and health utility detriments
      associated with OA were externally validated against other sources of evidence,
      and uncertainty resulting from key input parameters was quantified. The resulting
      lifetime and current population health-loss burden was consistent with estimates
      of previous studies. CONCLUSION: The new NZ-MOA model provides reliable estimates
      of the health loss associated with knee OA in the NZ population. The model
      structure is suitable for analysis of the effects of a range of potential
      treatments, and will be used in future work to evaluate the cost-effectiveness of
      recommended interventions within the NZ healthcare system.

PMID- 29331742
TI  - A sensitive and selective immunoaffinity column clean up coupled to UPLC-MS/MS
      for determination of trace methyl-3-quinoxaline-2-carboxylic acid in animal
      tissues.
AB  - This paper described a reliable and simple method for the selective determination
      of MQCA in animal tissues using ultra high performance liquid chromatography
      tandem mass spectrometry (UHPLC-MS/MS). A highly targeted immunoaffinity column
      was used for sample purification after enzymatic hydrolysis. The purified
      extracts were analyzed by reversed-phase HPLC-MS/MS in positive ESI and multiple
      reaction monitoring mode. The calibration curves showed good linearity with
      correlation coefficient (r2) larger than 0.995. The average recoveries at the
      spiked levels of 0.5, 2.0 and 20MUgkg-1 were 90.2% to 103.5% with intra-day and
      inter-day relatives standard deviations (RSD, n=6) ranging from 1.8% to 6.7% and
      3.5% to 7.6% respectively. The limit of quantification (LOQ) was 0.5MUgkg-1,
      which can fulfil the maximum residue level (MRL) of 4.0MUgkg-1 stipulated by the
      Agricultural Minister of China and the requirement of the confirmatory criteria
      according to the European Commission Decision 2002/657/EC. The method is
      sensitive, accurate, convenient and rapid, and has been successfully applied in
      real samples.

PMID- 29331743
TI  - Preliminary investigation of human exhaled breath for tuberculosis diagnosis by
      multidimensional gas chromatography - Time of flight mass spectrometry and
      machine learning.
AB  - Tuberculosis (TB) remains a global public health malady that claims almost 1.8
      million lives annually. Diagnosis of TB represents perhaps one of the most
      challenging aspects of tuberculosis control. Gold standards for diagnosis of
      active TB (culture and nucleic acid amplification) are sputum-dependent, however,
      in up to a third of TB cases, an adequate biological sputum sample is not readily
      available. The analysis of exhaled breath, as an alternative to sputum-dependent
      tests, has the potential to provide a simple, fast, and non-invasive, and ready
      available diagnostic service that could positively change TB detection. Human
      breath has been evaluated in the setting of active tuberculosis using thermal
      desorption-comprehensive two-dimensional gas chromatography-time of flight mass
      spectrometry methodology. From the entire spectrum of volatile metabolites in
      breath, three random forest machine learning models were applied leading to the
      generation of a panel of 46 breath features. The twenty-two common features
      within each random forest model used were selected as a set that could
      distinguish subjects with confirmed pulmonary M. tuberculosis infection and
      people with other pathologies than TB.

PMID- 29331741
TI  - Extracellular acidification induces ROS- and mPTP-mediated death in HEK293 cells.
AB  - The extracellular pH (pHe) is a key determinant of the cellular
      (micro)environment and needs to be maintained within strict boundaries to allow
      normal cell function. Here we used HEK293 cells to study the effects of pHe
      acidification (24h), induced by mitochondrial inhibitors (rotenone, antimycin A)
      and/or extracellular HCl addition. Lowering pHe from 7.2 to 5.8 reduced cell
      viability by 70% and was paralleled by a decrease in cytosolic pH (pHc),
      hyperpolarization of the mitochondrial membrane potential (Deltapsi), increased
      levels of hydroethidine-oxidizing ROS and stimulation of protein carbonylation.
      Co-treatment with the antioxidant alpha-tocopherol, the mitochondrial
      permeability transition pore (mPTP) desensitizer cyclosporin A and Necrostatin-1,
      a combined inhibitor of Receptor-interacting serine/threonine-protein kinase 1
      (RIPK1) and Indoleamine 2,3-dioxygenase (IDO), prevented acidification-induced
      cell death. In contrast, the caspase inhibitor zVAD.fmk and the ferroptosis
      inhibitor Ferrostatin-1 were ineffective. We conclude that extracellular
      acidification induces necroptotic cell death in HEK293 cells and that the latter
      involves intracellular acidification, mitochondrial functional impairment,
      increased ROS levels, mPTP opening and protein carbonylation. These findings
      suggest that acidosis of the extracellular environment (as observed in
      mitochondrial disorders, ischemia, acute inflammation and cancer) can induce cell
      death via a ROS- and mPTP opening-mediated pathogenic mechanism.

PMID- 29331744
TI  - Urinary metabolomics study the mechanism of Taohong Siwu Decoction intervention
      in acute blood stasis model rats based on liquid chromatography coupled to
      quadrupole time-of-flight mass spectrometry.
AB  - Taohong Siwu Decoction (TSD) is a classic prescription in traditional Chinese
      medicine and is widely used to promote blood circulation to remove blood stasis.
      However, the effect mechanisms are not yet well understood. Here, a urinary
      metabolomic approach based on liquid chromatography coupled to quadrupole time-of
      flight mass spectrometry (LC/Q-TOF-MS) was conducted to explore the changes in
      the endogenous metabolites and to assess the integral efficacy of TSD on acute
      blood stasis model rats. Then, parameters for hemorheology and coagulation
      functions were detected. Principal component analysis (PCA) and orthogonal
      partial least squares discriminate analysis (OPLS-DA) was used to investigate the
      global metabolite alterations and to evaluate the preventive effects of TSD in
      rats. Potential metabolite markers were found using OPLS-DA and t-test.
      Furthermore, metabolic pathway analysis was performed to construct metabolic
      networks. The results showed that TSD could significantly decrease whole blood
      viscosity and plasma viscosity. It also significantly prolonged partial
      thromboplastin time (APPT) and prothrombin time (PT), increased thrombin time
      (TT) and lowered fibrinogen content (FIB). Moreover, 24 potential metabolite
      markers of acute blood stasis were screened, and the levels were all reversed to
      different degrees after TSD administration. In metabolic networks, amino acid
      metabolism (arginine and proline metabolism; histidine metabolism; alanine,
      aspartate, and glutamate metabolism; phenylalanine, tyrosine, and tryptophan
      biosynthesis; phenylalanine metabolism) and lipid metabolism (glycerophospholipid
      metabolism; linoleic acid metabolism; alpha-linolenic acid metabolism) were
      closely related with the intervention mechanism of TSD on acute blood stasis. The
      urinary metabolomic approach can be applied to clarify the mechanism of TSD in
      promoting blood circulation to remove acute blood stasis and to provide the
      theoretical basis for further research on the therapeutic mechanism of TSD in
      clinical practice.

PMID- 29331745
TI  - Tumefactive Multiple Sclerosis Masquerading as High Grade Glioma.
AB  - Tumefactive multiple sclerosis is a demyelinating lesion that can
      radiographically mimic high-grade gliomas during acute episodes, thus affecting
      clinical decision making. A delay in appropriate diagnoses can result in
      unnecessary invasive resections. The following case is a patient with unilateral
      weakness and radiologic findings that were concerning for a high-grade glioma.
      Peripheral studies were equivocal. The decision was made to proceed with a
      stereotactic biopsy, yielding a definitive diagnosis of tumefactive demyelinating
      lesion (TDL). The patient responded robustly to medical management and made a
      full clinical recovery. While TDLs and gliomas may look radiologically identical
      during acute demyelinating episodes, unlike gliomas, TDLs will demonstrate
      evolvement over serial imaging and robust clinical response to high dose
      steroids. Clinicians should proceed with caution when considering invasive
      procedures with such lesions. Conservative medical management is often sufficient
      as seen in this patient. This case highlights the importance of timely diagnosis
      and management of TDLs.

PMID- 29331746
TI  - Canadian Neurosurgery Educators' Views on Stereotactic Radiosurgery in Residency
      Training.
AB  - OBJECTIVE: Despite the increasing prominence of stereotactic radiosurgery (SRS)
      in treating intracranial and spinal pathologies, there is currently a dearth of
      exposure to this modality in the neurosurgical residency. To address this gap,
      the aim of this study is to assess neurosurgery educators' views regarding the
      current state of SRS exposure, and to identify potential approaches to improve
      residency education in this domain. METHODS: Qualitative thematic analysis and
      constructivist grounded theory methodology were employed. Semistructured
      telephone-based interviews were conducted with current or past residency program
      directors, as well as current departmental chairs across neurosurgical
      departments in Canada. Interviews were transcribed and subjected to thematic
      analysis using open and axial coding. RESULTS: Of the 34 eligible participants,
      the overall response rate was 41.1% (14/34), with a 35.3% participation rate
      (12/34). Participants represented 9 of the 12 Canadian institutions surveyed. The
      majority of participants were current program directors (n = 8), followed by past
      program directors (n = 2), and departmental chairs (n = 2). Most respondents 75%
      (9/12) view an increasing role for SRS in neurosurgery. Unanimously, respondents
      endorse greater exposure to SRS during residency through formal residency
      rotations and engagement in interdisciplinary tumor boards to facilitate
      involvement in clinical decision-making. CONCLUSIONS: This is the first study to
      systematically collate neurosurgery educators' views on SRS in residency in
      Canada and demonstrates recognition of the discordance between SRS in practice
      and residency training. Neurosurgery educators broadly endorse increased exposure
      to this modality. Future work is needed to delineate the requirements necessary
      to achieve adequate competency in SRS.

PMID- 29331747
TI  - Dural-Based Cavernous Malformation at the Cerebral Convexity: Report of Two
      Pediatric Patients.
AB  - BACKGROUND: Intracranial cavernous malformations (CMs) are usually located at the
      cerebral parenchyma; dural-based CMs outside the middle fossa are rarely
      reported. To our knowledge, dural-based CMs located at the cerebral convexity are
      even rarer in that only 2 pediatric cases have ever been reported. In this
      report, we present 2 extremely rare cases of dural-based CMs at the cerebral
      convexity in pediatric patients. The clinical course, radiologic and pathologic
      features, treatment, and follow-up are described. CASE DESCRIPTION: The first
      case is a 6-year-old boy who presented with headache and vomiting and was found
      to have an acute subdural hematoma and space-occupying lesion. Intraoperative
      findings and histologic examination were consistent with a CM. He experienced an
      uneventful postoperative recovery. The second case is a 43-day-old female neonate
      who presented with a progressively enlarging neoplasm at the right occipital
      region since birth. Computed tomography of the head performed at admission showed
      a slight hyperdense occupying lesion communicating between the intra- and
      extracranial cavity through a skull defect. The lesion was resected en bloc and
      histologic examination was in accord with a CM. CONCLUSIONS: The clinical
      manifestations and radiologic characteristics of dural-based CMs are nonspecific.
      Unlike that of their cerebral parenchymal counterparts, the radiologic appearance
      of dural-based CMs is confusing and misleading. Surgical resection is the primary
      treatment selection for dural-based CMs. In cases with no close relationship to
      dural sinuses, complete surgical resection with minimal blood loss and few
      neurologic deficits could be easily achieved.

PMID- 29331748
TI  - Safety and efficacy of anti-programmed death 1 antibodies in patients with cancer
      and pre-existing autoimmune or inflammatory disease.
AB  - OBJECTIVE: Patients with autoimmune or inflammatory disease (AID) are susceptible
      to immune-related adverse events (irAEs) when treated with immune check-point
      inhibitors (ICIs). We decided to analyse the safety and effectiveness of anti-PD
      1 antibodies in AID patients and look for an association between the presence of
      pre-existing AID and the clinical outcome. METHODS: In a prospective study of the
      REISAMIC registry of grade >=2 irAEs occurring in ICI-treated patients, we
      studied the associations between pre-existing AID on one hand and irAE-free
      survival, overall survival and best objective response rate on the other.
      RESULTS: We identified 45 patients with 53 AIDs in REISAMIC. The cancer diagnoses
      included melanoma (n = 36), non-small-cell lung cancer (n = 6) and others (n =
      3). The most frequent pre-existing AIDs were vitiligo (n = 17), psoriasis (n =
      12), thyroiditis (n = 7), Sjogren syndrome (n = 4) and rheumatoid arthritis (n =
      2). Twenty patients (44.4%) presented with at least one irAE: eleven of these
      were associated with a pre-existing AID ('AID flare'). Treatment with anti-PD-1
      antibodies was maintained in 15 of the 20 patients with an irAE. The IrAE-free
      survival time was significantly shorter in AID patients (median: 5.4 months) than
      in AID-free patients (median: 13 months, p = 2.1 * 10-4). The AID and AID-free
      groups did not differ significantly with regard to the overall survival time and
      objective response rate (p = 0.38 and 0.098, respectively). CONCLUSION: In
      patients treated with anti-PD-1 antibody, pre-existing AID was associated with a
      significantly increased risk of irAEs. Our results indicate that cancer
      treatments with anti-PD-1 antibodies are just as effective in AID patients as
      they are in AID-free patients.

PMID- 29331749
TI  - Paediatric dysgerminoma: Results of three consecutive French germ cell tumours
      clinical studies (TGM-85/90/95) with late effects study.
AB  - METHODS: French patients (<=18years) treated for dysgerminoma between 1985 and
      2005 in TGM-85, 90, 95 protocols were included. Treatment was based on primary
      unilateral oophorectomy followed by prophylactic lymph node irradiation (1985
      1998) or a wait-and-see strategy (1998-2005) for localised completely resected
      tumours (pS1) or by platinum-based chemotherapy for advanced diseases. RESULTS:
      Forty-eight patients (median age 12.8 years) were included. Six patients had
      gonadal dysgenesis. Two had bilateral dysgerminoma. Twenty-eight patients had
      loco-regional dissemination, seven with para-aortic lymph nodes. None had distant
      metastases. Primary surgery was performed in 47/48 patients. Among the 15
      patients with pS1 tumour: seven did not receive adjuvant treatment, six had lymph
      node irradiation and two received chemotherapy. Among the 32 patients with
      advanced tumour, 31 received cisplatinum-based (n = 25) or carboplatin-based (n =
      8) regimen with lymph node irradiation for one of them and one did not receive
      adjuvant treatment. With a median follow-up of 14 years, all patients are alive
      in complete remission. Five events occurred: 2 contralateral dysgerminomas, 1
      peritoneal relapse and 2 second neoplasms (teratoma and melanoma). Bilateral
      oophorectomy was necessary for 12 patients. Desire of pregnancy was expressed for
      17/36 patients with unilateral oophorectomy, which succeeded in 13 cases (5
      medically assisted). 2/17 had ovarian failure. The renal function was normal in
      24/25 evaluated patients treated with platinum, ifosfamide or irradiation. The
      hearing function was evaluated on 17/36 patients treated with platinum: 12 Brock
      grade-0, 3 brock grade-1 and 2 grade-4. CONCLUSION: Dysgerminoma has an excellent
      prognosis even in advanced cases with conservative surgery and platinum-based
      chemotherapy. However the disease and/or treatment resulted in a high rate of
      bilateral oophorectomies and a significant impact on future fertility.

PMID- 29331750
TI  - Phosphoinositide 3-kinase inhibitors in advanced breast cancer: A systematic
      review and meta-analysis.
AB  - Phosphoinositide 3-kinase (PI3K) inhibitors may overcome drug resistance and
      improve advanced breast cancer (ABC) outcomes. We conducted a systematic review
      and meta-analysis to assess the efficacy and safety of adding a PI3K inhibitor to
      the standard of care (SOC) treatment in ABC. The electronic databases Ovid,
      PubMed, Cochrane Central Register of Controlled Trials and Embase, were searched
      for relevant randomised trials. Pooled hazard ratios (HRs) for progression-free
      survival (PFS) and pooled risk ratios (RRs) for objective response rates (ORRs),
      disease control rates (DCRs) and toxicity were meta-analysed using the Mantel
      Haenszel method and generic inverse variance. Five studies were included. In
      unselected patients, the addition of a PI3K inhibitor decreased the risk of
      progression by 21% (2329 participants, HR = 0.79; 95% confidence interval [CI],
      0.71-0.88). A marginal improvement in ORR (2329 participants, RR = 1.26; 95% CI,
      1.01-1.57) and no improvement in DCR (2146 participants, RR = 1.05; 95% CI, 0.94
      1.18) were achieved with a significant increase in toxicity of any grade (2386
      participants, RR = 1.05; 95% CI, 1.03-1.06) and of grade III and higher (2386
      participants, RR = 1.91; 95% CI, 1.76-2.08). A PFS benefit was seen in patients
      with and without PI3K pathway activation assessed on tumour and only in patients
      with an activated PI3K pathway when it was assessed from the plasma using
      circulating tumour DNA (ct-DNA) analysis. The addition of a PI3K inhibitor
      decreases the risk of progression in unselected ABC patients and particularly in
      patients with an activated PI3K pathway detected on ct-DNA analysis. However,
      their significant dose-limiting toxicity is a limiting factor. Selective PI3K
      inhibitors are being tested to assess whether these better-tolerated agents have
      a role in ABC treatment.

PMID- 29331752
TI  - Synthesis of gold(I) phosphine complexes containing the 2-BrC6F4PPh2 ligand:
      Evaluation of anticancer activity in 2D and 3D spheroidal models of HeLa cancer
      cells.
AB  - Newly synthesised mononuclear gold complexes containing the 2-BrC6F4PPh2 ligand
      have been fully characterised and their anticancer activity towards five human
      tumor [prostate (PC3), glioblastoma (U87MG), cervical (HeLa), fibrosarcoma
      (HT1080), ovarian (SKOV-3)] and normal human embryonic kidney (Hek-293T) cell
      lines investigated. Some of the synthesised gold complexes displayed higher
      cytotoxicity than cisplatin towards PC-3, HeLa and U87MG cells and inhibited the
      thioredoxin reductase (TrxR) enzyme, which is considered a potential target for
      new compounds in cancer treatment. The more physiologically relevant tumor
      spheroid assay demonstrated the superior potency of these gold phosphine
      complexes in inhibiting the growth of cervical carcinoma cell line HeLa (3D)
      spheroidal models. The mechanism of cell death was shown to be apoptotic cell
      death through cell cycle arrest, mitochondrial membrane depolarisation and
      increased ROS production.

PMID- 29331751
TI  - Comprehensive genomic profiling of head and neck squamous cell carcinoma reveals
      FGFR1 amplifications and tumour genomic alterations burden as prognostic
      biomarkers of survival.
AB  - BACKGROUND: We aimed at identifying deleterious genomic alterations from
      untreated head and neck squamous cell carcinoma (HNSCC) patients, and assessing
      their prognostic value. PATIENTS AND METHODS: We retrieved 122 HNSCC patients who
      underwent primary surgery. Targeted NGS was used to analyse a panel of 100 genes
      selected among the most frequently altered genes in HNSCC and potential
      therapeutic targets. We selected only deleterious (activating or inactivating)
      single nucleotide variations, and copy number variations for analysis. Univariate
      and multivariate analyses were performed to assess the prognostic value of
      altered genes. RESULTS: A median of 2 (range: 0-10) genomic alterations per
      sample was observed. Most frequently altered genes involved the cell cycle
      pathway (TP53 [60%], CCND1 [30%], CDKN2A [25%]), the PI3K/AKT/MTOR pathway
      (PIK3CA [12%]), tyrosine kinase receptors (EGFR [9%], FGFR1 [5%]) and cell
      differentiation (FAT1 [7%], NOTCH1 [4%]). TP53 mutations (p = 0.003), CCND1
      amplifications (p = 0.04), CDKN2A alterations (p = 0.02) and FGFR1 amplifications
      (p = 0.003), correlated with shorter overall survival (OS). The number of genomic
      alterations was significantly higher in the HPV-negative population (p = 0.029)
      and correlated with a shorter OS (p < 0.0001). Only TP53 mutation and FGFR1
      amplification status remained statistically significant in the multivariate
      analysis. CONCLUSION: These results suggest that genomic alterations involving
      the cell cycle (TP53, CCND1, CDKN2A), as well as FGFR1 amplifications and tumour
      genomic alterations burden are prognostic biomarkers and might be therapeutic
      targets for patients with HNSCC.

PMID- 29331753
TI  - An iridium (III) complex as potent anticancer agent induces apoptosis and
      autophagy in B16 cells through inhibition of the AKT/mTOR pathway.
AB  - A new ligand THPDP (THPDP = 11-(6,7,8,9-tetrahydrophenazin-2-yl)dipyrido[3,2
      a:2',3'-c]phenazine) and its iridium(III) complex [Ir(ppy)2(THPDP)]PF6 (Ir-1) was
      synthesized and characterized by elemental analysis, IR, ESI-MS, 1H NMR and 13C
      NMR. The cytotoxicity in vitro of the complex against cancer cells B16, A549, Eca
      109, SGC-7901, BEL-7402 and normal NIH 3T3 cell lines was evaluated using MTT
      method. The IC50 values of the complex toward B16, A549 and Eca-109 cells are 1.0
      +/- 0.02, 1.4 +/- 0.03 and 1.6 +/- 0.06 MUM, respectively. The apoptosis was
      investigated with AO/EB and DAPI staining methods. The complex shows strong
      ability to inhibit the cell growth in B16, A549 and Eca-109 cells. Ir-1 can
      induce apoptosis, increase the intracellular ROS level, and cause a decrease in
      the mitochondrial membrane potential. The intracellular Ca2+ level and the
      release of cytochrome c were studied under a fluorescent microscope. The cell
      invasion and autophagy were also performed, and the cell cycle arrest was assayed
      by flow cytometry. The expression of Bcl-2 family proteins, PI3K, AKT, mTOR, P
      mTOR was investigated by western blot. The results show that the complex induces
      apoptosis through ROS-mediated mitochondria dysfunction and inhibition of
      AKT/mTOR pathways. These findings are helpful for design and synthesis of
      iridium(III) complexes as potent anticancer drugs.

PMID- 29331754
TI  - Synthesis and bioevaluation and doking study of 1H-pyrrolo[2,3-b]pyridine
      derivatives bearing aromatic hydrazone moiety as c-Met inhibitors.
AB  - Two series of aromatic hydrazone derivatives bearing 1H-pyrrolo[2,3-b]pyridine
      moiety (7a-r, 8a-i, 12a-b, 13a-c, 16a-d and 17a-e) were designed, synthesized and
      evaluated for the IC50 values against four cancer cell lines (A549, HepG2, MCF
      7and PC-3). Two selected compounds (7c and 17e) were further evaluated for the
      activity against c-Met, Flt-3, VEGFR-2 and EGFR kinases. The data indicated that
      targets compounds were selective for c-Met kinase. And the most promising
      compound 7c was further studied in terms of dose-dependent, time-dependent and
      cell apoptosis. Most of the compounds showed excellent cytotoxicity activity,
      especially the most promising compound 7c with the IC50 values of 0.82 +/- 0.08
      MUM, 1.00 +/- 0.11 MUM, 0.93 +/- 0.28 MUM and 0.92 +/- 0.17 MUM against A549,
      HepG2, MCF-7 and PC-3 cell lines and 0.506 MUM against c-Met kinase. Structure
      activity relationships (SARs) and docking studies indicated that the activities
      of the phenyl hydrazone derivatives (7a-r and 8a-i) were superior to that of the
      heterocyclic hydrazone series (12a-b, 13a-c, 16a-d and 17a-e). What's more, the
      further studies indicated that the target compounds can induce apoptosis of A549
      cells and arrest efficiently the cell cycle progression in G2/M phase of A549
      cells.

PMID- 29331756
TI  - 'You're repulsive': Limits to acceptable drunken comportment for young adults.
AB  - BACKGROUND: Researchers have described a 'culture of intoxication' among young
      people. Yet drunkenness remains a socially risky practice with potential to evoke
      emotions of irritation and even disgust. We consider intoxicated practices that
      young adults in Melbourne, Australia, described as distasteful, to identify
      contemporary cultural forces that constrain intoxication and limit how it is
      enacted. METHOD: Interviews were conducted with 60 participants in Melbourne,
      Australia, each with recent drinking experience. Participants were asked to
      provide accounts of moments when they regarded their own or others' drunken
      comportment as unsociable or unpleasant. Transcripts were analysed to identify
      recurrent themes. RESULTS: Despite amusement when recounting drunken antics,
      almost everyone in the study identified some discomfort at their own or other's
      drunkenness. We describe four interacting domains where lines delineating
      acceptable comportment appear be drawn. The first concerns intoxicated practices.
      Unpleasant drunken comportment often entailed a sense that the drunk person had
      disturbed others through an overflow of the self - extruding intimacy, sexuality,
      violence or bodily fluids. The second domain was gendering, with women vulnerable
      to being regarded as sexually inappropriate, and men as threatening. Third, the
      settings where intoxicated behaviour occurred influenced whether intoxicated
      people risked censure. Finally, the relationships between the drunk person and
      others, including their respective social positions and drinking patterns, shaped
      how they were perceived. CONCLUSION: The capacity of alcohol to render people
      more open to the world is both sought and reviled. It is important to recognise
      that there remain limits on acceptable drunken comportment, although these are
      complex and contingent. These limits are enforced via people's affective
      responses to drunkenness. This is form of alcohol harm reduction that occurs
      outside of public health intervention. Thus, cultures that constrain drinking
      should be supported wherever it is possible to do so without reinforcing
      stigmatising identities.

PMID- 29331757
TI  - Hedging bets: Applying New Zealand's gambling machine regime to cannabis
      legalization.
AB  - Cannabis legalization is often falsely depicted as a binary choice between status
      quo prohibition and legalizing production and distribution by (regulated) for
      profit industry. There are, however, many more prudent architectures for
      legalization, such as restricting production and distribution licenses to not-for
      profit entities. Wilkins describes how New Zealand applied that concept to
      gambling machines and proposes a parallel for cannabis legalization. Greater
      investment in proposing good designs along these lines, including attending to
      governance structures, would be valuable.

PMID- 29331755
TI  - Sphingosine-1-phosphate protects human ovarian follicles from apoptosis in vitro.
AB  - OBJECTIVE(S): We aimed to analyze if anti-apoptotic agent sphingosine-1-phosphate
      offers protection against in vitro follicle atresia during culture of human
      ovarian cortical samples. STUDY DESIGN: A translational research study of ex-vivo
      and in-vitro models of human ovarian tissue. MATERIAL AND METHODS: Ovarian
      cortical tissue fragments (1 * 0.5 cm) were obtained from young patients (n = 15
      mean age +/- SD: 29.4 +/- 2.5) undergoing laparoscopic excision of benign ovarian
      cysts. The samples were cultured for 4 days in 24-well format culture plate using
      conventional culture techniques. S1P was added to culture media at 200 and 400
      MUM concentrations. At the end of culture period the samples were processed for
      both histomorphological assessment and detection of apoptosis with
      immunohistochemistry and western blot methods using apoptosis marker cleaved
      caspase-3. In vitro estradiol (E2) and AMH productions of the samples were
      measured with ELISA. Follicle counts were expressed as the mean number of
      follicles per mm2. RESULTS: The mean numbers of primordial and secondary
      follicles were 3.2 +/- 0.4 and 0.7 +/- 0.2 respectively, in the fresh fixed
      uncultured samples. After four days of culture their numbers were significantly
      decreased to 0.8 +/- 0.2 (p < 0.01) and 0.1 +/- 0.05 (p < 0.05) respectively, in
      the control samples cultured without S1P compared to fresh fixed samples. S1P
      treatment decreased follicle atresia and significantly higher number of
      primordials (2.3 +/- 0.3, p < 0.01) and secondary follicles (0.5 +/- 0.1, p <
      0.05) survived in the samples after 4 day culture period compared to those
      cultured without S1P. In line with this there was dose-dependent decrease in the
      protein expression of cleaved caspase-3 on western blot and in the number of
      apoptotic follicles stained positive for cleaved caspase-3 on
      immunohistochemistry in the samples incubated with S1P at 200 and 400 MUM
      concentrations. Furthermore, those samples incubated with S1P produced
      significantly higher amounts of E2 (2339 +/- 321 vs. 1156 +/- 125 pg/mL
      respectively, p < 0.01) compared to control samples. CONCLUSIONS: These results
      suggest that S1P promotes follicle survival in human ovarian cortical samples in
      vitro.

PMID- 29331758
TI  - Caspase-3/MAPK pathways as main regulators of the apoptotic effect of the phyto
      mediated synthesized silver nanoparticle from dried stem of Eleutherococcus
      senticosus in human cancer cells.
AB  - Siberian ginseng (Eleutherococcus senticosus) was used for the synthesis of an
      ecofriendly silver nanoparticle (Sg-AgNP), which has exhibited antibacterial,
      antioxidant effect and lower cytotoxicity to normal cells in comparison to human
      cancer cells. Although, the potential anticancer activity of Sg-AgNP has not been
      determined. In this study, two cancer cell lines were used to evaluate the
      cytotoxicity and apoptotic effect of Sg-AgNP along with the determination of the
      role of the Caspase-3 / p38 MAPK pathways. Results shown that Sg-AgNP reduced the
      cell viability of colon cancer cells HT29 and lung cancer cells A549. The
      cytotoxic effect was higher than the effect exhibited by a commercial silver
      nanoparticle and Cisplatin. Reactive oxygen species were observed to be superior
      in both cell lines in the presence of Sg-AgNPs than c-AgNPs and Cisplatin. It was
      observed an activation of MAPK14 gene and phosphorylation of p38 MAPK protein in
      both cell lines induced by Sg-AgNPs treatment. Furthermore, induction of
      morphological changes in the nucleus was done by Sg-AgNPs at 10 MUg/mL in both
      cell lines. On the other hands, the activation of CASP3 gene and Caspase-3
      protein was observed in HT29 cells but only at protein level in A549 cells. These
      results, suggest that Sg-AgNPs anticancer potential activity might be linked to
      the induction of apoptosis though the generation of ROS by activation of the
      Caspase-3/p38 MAPK pathway.

PMID- 29331759
TI  - Astragaloside IV inhibits cell migration and viability of hepatocellular
      carcinoma cells via suppressing long noncoding RNA ATB.
AB  - Astragaloside IV (AS-IV), the major active component of Astragalus membranaceus,
      has shown attractive anticancer effects in certain cancers. However, the roles
      and action mechanisms of AS-IV in hepatocellular carcinoma (HCC) are largely
      unclear. Long noncoding RNAs (lncRNAs) are recently revealed to have crucial
      roles in HCC initiation and progression, but whether lncRNAs participate in the
      anticancer roles of AS-IV are unknown. In this study, we demonstrated that AS-IV
      significantly downregulated lncRNA-ATB expression in a dose- and time-dependent
      manner in HCC cells. Through downregulating lncRNA-ATB, AS-IV repressed
      epithelial-mesenchymal transition (EMT) and migration of HCC cells. Furthermore,
      through downregulating lncRNA-ATB, AS-IV inactivated IL-11/STAT3 signaling,
      induced HCC cell apoptosis, and decreased HCC cell viability. Overexpression of
      lncRNA-ATB reversed the effects of AS-IV on HCC cell migration, EMT, cell
      apoptosis, cell viability, and IL-11/STAT3 signaling. Taken together, our results
      showed that AS-IV inhibited migration and cell viability of HCC cells via
      downregulating lncRNA-ATB. Thus, our data provided a novel molecular basis for
      the applications of AS-IV in the therapy of HCC.

PMID- 29331760
TI  - Inotodiol suppresses proliferation of breast cancer in rat model of type 2
      diabetes mellitus via downregulation of beta-catenin signaling.
AB  - Breast cancer is amongst the most common cancers causing death of women
      worldwide. Breast cancer occurrence is more prominent in people with diabetes. A
      recent trend is management of diabetes and cancer has evolved to be natural
      remedy including single molecule therapy or combination. In this study, we
      investigated the effect of inotodiol on breast cancer growth in diabetic
      conditions. Inotodiol is a lanostane triterpenoid found in natural resources like
      edible mushroom Inonotus obliquus. We established a rat model of diabetic-breast
      cancer by treating female Sprague-Dawley rats with streptazotocin (STZ) at 35
      mg/kg followed by induction of breast cancer by administration of 7,12
      dimethylbenz(a)anthracene (DMBA) at 10 mg/kg. Diabetes development in
      experimental rats was confirmed by measuring fasting blood glucose levels and
      oral glucose tolerance test (OGTT), and other biochemical assays were performed.
      Histological evaluation of pancreas was performed. The proliferation of breast
      tumor was measured by immunohistochemical staining for PCNA, cleaved-caspase-3
      and TUNEL staining for apoptosis, and beta-catenin. Results of the study
      demonstrate that inotodiol lowered the blood glucose levels in SD rats as well as
      reduced plasma levels of cholesterol, triglyceride, and high-density lipoprotein.
      The tumor proliferation marker PCNA was reduced by inotodiol. It downregulated
      the expression of beta-catenin and its downstream targets (c-Myc and Cyclin D1)
      followed by apoptosis induction. Conclusively, results suggest that inotodiol
      regulates blood glucose levels in diabetic rats and then controls proliferation
      of breast tumor progression by inducing apoptosis via downregulation of beta
      catenin signaling. It further suggests that inotodiol can be a preventive
      approach in managing dietary chronic conditions like diabetic-breast cancer.

PMID- 29331761
TI  - Prevention of articular cartilage degeneration in a rat model of monosodium
      iodoacetate induced osteoarthritis by oral treatment with Withaferin A.
AB  - Withaferin A (WFA), a highly oxygenated withanolide is used for anti
      osteoporotic, fracture healing, obesity control as medicine and dietary
      supplement in Ayurveda and Unani medicine but its potential remains to be
      investigate for the osteoarthritis studies. In the present study, chondro
      protective effects of WFA, under in vitro and in vivo conditions were evaluated.
      In-vitro pharmacological activity of WFA was tested on rat articular chondrocytes
      through MTT, DPPH, different staining, FACS and translation studies. In-vivo
      studies of WFA were evaluated through monosodium iodoacetate (MIA) induced
      osteoarthritis studies. DPPH assay, alcian blue and toluidine blue staining
      indicated the chondrogenic potential of WFA. Similarly, WFA enhance
      chondrogenesis through up-regulation of SOX9 protein. In addition, WFA reduced
      the ROS generation, mitochondrial depolarization and apoptosis induced by
      inflammatory cytokines IL-1beta and TNF-alpha. Furthermore, WFA treatment in MIA
      treated rats alleviated cartilage erosion and improvement in sub-chondral bone
      micro-architecture by decrease in Tissue volume (~32%), and trabecular bone
      pattern factor (~28%). Taken together, our study provides convincing evidence for
      the candidature of WFA (10 mg kg-1 day-1) as a potential agent for the treatment
      of cartilage degenerative diseases like osteoarthritis.

PMID- 29331762
TI  - Suppression of Capn4 by microRNA-1271 impedes the proliferation and invasion of
      colorectal cancer cells.
AB  - Accumulating evidence has suggested that calpain small subunit 1 (Capn4) plays an
      important role in the development and progression of malignant tumors. However,
      little is known about the role of Capn4 in colorectal cancer (CRC). In this
      study, we aimed to investigate the potential role of Capn4 in CRC and the
      regulation of Capn4 by microRNAs (miRNAs). Here, we found that Capn4 expression
      was highly up-regulated in CRC cell lines. Knockdown of Capn4 by siRNA
      significantly inhibited the proliferation and invasion of CRC cell lines.
      Furthermore, knockdown of Capn4 suppressed Wnt signaling in CRC cells.
      Interestingly, Capn4 was found to be a target gene of miR-1271, a tumor
      suppressive miRNA. The results showed that miR-1271 negatively regulated Capn4
      expression in CRC cells. An inverse correlation between miR-1271 and Capn4 was
      also shown in CRC clinical tissues. Moreover, the overexpression of miR-1271
      suppressed the proliferation, invasion and Wnt signaling of CRC cells.
      Importantly, we found that the restoration of Capn4 expression significantly
      reversed the antitumor effects of miR-1271 in CRC cells. Overall, these results
      suggest that miR-1271 inhibits the proliferation and invasion of CRC cells by
      down-regulating Capn4. Our study suggests that Capn4 and miR-1271 may serve as
      potential therapeutic targets for the treatment of CRC.

PMID- 29331763
TI  - Inhibition of isoprenylcysteine carboxylmethyltransferase sensitizes common
      chemotherapies in cervical cancer via Ras-dependent pathway.
AB  - Isoprenylcysteine carboxylmethyltransferase (Icmt) catalyzes the last step of
      post-translational protein prenylation, which is essential for the stability and
      proper functions of many oncogenic proteins, such as Ras. Despite extensive
      studies on the roles of Icmt in tumor transformation and progression, little is
      known on the involvement ofIcmt in the development of tumor resistance to
      chemotherapy. Here we show the upregulation of Icmt as a persistent response to
      chemotherapy in cervical cancer cells. In-depth functional analysis demonstrated
      that Icmt inhibition significantly inhibited growth, induced apoptosis and
      augmented the inhibitory effects of chemotherapy drugs in cervical cancer in cell
      culture system and xenograft mouse model. Importantly, combination of Icmt
      specific inhibitor cysmethynil with doxorubicin or paclitaxel at sublethal
      concentration achieved almost full inhibition of tumor cell growth and survival.
      The remarkable synergy between chemotherapy drugs and Icmt inhibition in cervical
      cancer cells is likely due to the additional suppression of Ras and its
      downstream signaling pathways. We are the first to demonstrate the contribution
      of Icmt in tumor cells in response to chemotherapy. Our work also highlights Icmt
      inhibition as a sensitizing strategy for the treatment of cervical cancer or
      other Ras-driven tumors.

PMID- 29331764
TI  - Synthesis: Small library of hybrid scaffolds of benzothiazole having hydrazone
      and evaluation of their beta-glucuronidase activity.
AB  - Due to the great biological importance of beta-glucuronidase inhibitors, here in
      this study, we have synthesized a library of novel benzothiazole derivatives (1
      30), characterized by different spectroscopic methods and evaluated for beta
      glucuronidase inhibitory potential. Among the series sixteen compounds i.e.1-6,
      8, 9, 11, 14, 15, 20-23 and 26 showed outstanding inhibitory potential with IC50
      value ranging in between 16.50 +/- 0.26 and 59.45 +/- 1.12 when compared with
      standard d-Saccharic acid 1,4-lactone (48.4 +/- 1.25 uM). Except compound 8 and
      23 all active analogs showed better potential than the standard. Structure
      activity relationship has been established.

PMID- 29331765
TI  - 5,6-Dihydropyrimidine-1(2H)-carbothioamides: Synthesis, in vitro GABA-AT
      screening, anticonvulsant activity and molecular modelling study.
AB  - Even after considerable advances in the field of epilepsy treatment, convulsions
      are inefficiently controlled by standard drug therapy. Herein, a series of
      pyrimidine-carbothioamide derivatives 4(a-t) was designed as anticonvulsant
      agents by doing some important structural modifications in well-known
      anticonvulsant drugs. Two classical animal models were used for the in vivo
      anticonvulsant screening, maximum electroshock seizure (MES) and subcutaneous
      pentylenetetrazole (scPTZ) models; followed by motor impairment study by rotarod
      method. The most active compound 4g effectively suppressed seizure effect in both
      the animal models with median doses of 15.6 mg/kg (MES ED50), 278.4 mg/kg (scPTZ
      ED50) and 534.4 mg/kg (TD50) with no sign of neurotoxicity. Furthermore, in vitro
      GABA-AT enzyme activity assay of 4g showed inhibitory potency (IC50) of 12.23
      MUM. The docking study also favored the animal studies.

PMID- 29331766
TI  - Roflumilast, type 4 phosphodiesterase inhibitor, attenuates inflammation in rats
      with ulcerative colitis via down-regulation of iNOS and elevation of cAMP.
AB  - BACKGROUND: Roflumilast (Rof), a phosphodiesterase 4 (PDE4) inhibitor, has been
      shown to be an effective agent in inflammatory diseases and marketed for chronic
      obstructive pulmonary disease. OBJECTIVE: This study was conducted to examine the
      potential anti-inflammatory effects of Rof in dextran sulphate sodium (DSS)
      induced ulcerative colitis (UC) in rats and to investigate the molecular
      mechanisms underlying these effects. METHODS: Forty male Wistar rats were divided
      into four groups: normal control, colitis group (rats received 5% DSS in their
      drinking water continuously for 7 days), Rof group, and sulfasalazine (SLZ)
      group. The Rof (5 mg/kg) and SLZ (500 mg/kg) groups underwent pretreatment with
      DSS one week ahead of DSS challenge and parallel with DSS. Colitis was determined
      by assessing colon length, weight loss, histologic colon score, quantifying the
      concentration of tumor necrosis factor alpha (TNF-alpha), nitric oxide (NO),
      cyclic adenosine monophosphate (cAMP), myeloperoxidase (MPO) activity and
      inducible nitric oxide synthase (iNOS) gene expression in colon tissue. RESULTS:
      Rof attenuated the severity of colitis as evidenced by increased colon length,
      prevention of body weight loss, and improved colon histologic score compared to
      DSS group. Rof also suppressed the inflammatory response induced in DSS colitis
      group by decreasing colon concentration of TNF-alpha, NO and MPO activity and
      down- regulation of iNOS gene expression. The level of cAMP was increased by Rof
      compared to DSS group. The obtained results of Rof were comparable to those
      exerted by SLZ. CONCLUSION: These findings revealed the beneficial effects of Rof
      in alleviating inflammation in DSS colitis.

PMID- 29331767
TI  - Lessons from simple marine models on the bacterial regulation of eukaryotic
      development.
AB  - Molecular cues from environmental bacteria influence important developmental
      decisions in diverse marine eukaryotes. Yet, relatively little is understood
      about the mechanisms underlying these interactions, in part because marine
      ecosystems are dynamic and complex. With the help of simple model systems,
      including the choanoflagellate Salpingoeca rosetta, we have begun to uncover the
      bacterial cues that shape eukaryotic development in the ocean. Here, we review
      how diverse bacterial cues-from lipids to macromolecules-regulate development in
      marine eukaryotes. It is becoming clear that there are networks of chemical
      information circulating in the ocean, with both eukaryotes and bacteria acting as
      nodes; one eukaryote can precisely respond to cues from several diverse
      environmental bacteria, and a single environmental bacterium can regulate the
      development of different eukaryotes.

PMID- 29331768
TI  - The cholinergic anti-inflammatory pathway: an innovative treatment strategy for
      respiratory diseases and their comorbidities.
AB  - Over the past few decades, it has been clarified that the nervous system and
      immune system have overlapping distributions and their interactions are critical
      in the regulation of immunological and inflammatory responses. The cholinergic
      anti-inflammatory pathway, including the parasympathetic nerve systems and
      humoral factors orchestrate the immune responses to protect the body during
      infection and tissue injury. Recent investigations have attempted to clarify how
      the parasympathetic nerve systems attenuate the systemic inflammatory responses
      and identified the alpha7 nicotinic acetylcholine receptor (alpha7nAChR) as a
      crucial target for attenuating the release of inflammatory cytokines from
      inflammatory cells including macrophages and dendritic cells. This modulatory
      circuit pathway possibly exists in the lungs and might be involved in regulating
      inflammation and immunity during infection and other inflammatory lung diseases
      including asthma and COPD, which means that modulation of the cholinergic anti
      inflammatory pathway is a possible therapeutic target for lung diseases.

PMID- 29331769
TI  - Source identification of uranium-containing materials at mine legacy sites in
      Portugal.
AB  - Whilst prior nuclear forensic studies have focused on identifying signatures to
      distinguish between different uranium deposit types, this paper focuses on
      providing a scientific basis for source identification of materials from
      different uranium mine sites within a single region, which can then be
      potentially used within nuclear forensics. A number of different tools, including
      gamma spectrometry, alpha spectrometry, mineralogy and major and minor elemental
      analysis, have been utilised to determine the provenance of uranium mineral
      samples collected at eight mine sites, located within three different uranium
      provinces, in Portugal. A radiation survey was initially conducted by foot and/or
      unmanned aerial vehicle at each site to assist sample collection. The results
      from each mine site were then compared to determine if individual mine sites
      could be distinguished based on characteristic elemental and isotopic signatures.
      Gamma and alpha spectrometry were used to differentiate between samples from
      different sites and also give an indication of past milling and mining
      activities. Ore samples from the different mine sites were found to be very
      similar in terms of gangue and uranium mineralogy. However, rarer minerals or
      specific impurity elements, such as calcium and copper, did permit some
      separation of the sites examined. In addition, classification rates using linear
      discriminant analysis were comparable to those in the literature.

PMID- 29331770
TI  - Women's satisfaction with mammography and predictors of participation in an
      organized breast cancer screening program: Perspectives of a Local Health Unit in
      Rome.
AB  - OBJECTIVES: The aims of the study were to evaluate satisfaction with the
      mammography service of the Local Health Unit RMA (Rome, Lazio Region) among women
      who have attended the program and to identify the predictors of participation.
      STUDY DESIGN: Cross-sectional study. METHODS: A telephone-based questionnaire was
      administered to women eligible for mammography screening. The respondents were
      randomly selected and interviewed by the health center staff. RESULTS: A total of
      502 women were interviewed, of which 264 (52.6%) have attended the screening
      program at least once. The attendees received the invitation letter more often
      than the non-attendees (88.3% vs 77.7%; P = 0.002), were more willing to
      participate (85.6% vs 69.3%; P = 0.001), they considered the letter very clear
      (15% vs 10.8%; P = 0.003), and information obtained through the hotline
      appropriate (64.7% vs 56.7%; P = 0.002). Overall satisfaction was high. Critical
      issues were lack of response from the hotline staff, medium-long waiting time for
      the results and further examinations. Age >61 years (odds ratio [OR] = 2.747; 95%
      confidence interval [CI] = 1.842-4.096), receiving the invitation letter (OR =
      2.539; 95% CI = 1.519-4.242), and intention to participate (OR = 3.086; 95% CI =
      1.938-4.915) were significantly associated with participation in the screening
      program. CONCLUSIONS: Women's satisfaction with mammography is an important
      aspect of service utilization. Implementation of strategies to reduce waiting
      time, increase operating hours, and improve the invitation procedure and the
      hotline service could enhance satisfaction and attendance rate.

PMID- 29331771
TI  - Quarantine and the U.S. military response to the Ebola crisis: soldier health and
      attitudes.

PMID- 29331772
TI  - Alcohol-induced risk behaviors among Brazilian nightclub patrons: a latent class
      analysis.
AB  - OBJECTIVE: The aim of this study is to identify risk behavior profiles associated
      with alcohol consumption among patrons during or just after departure from
      nightclubs in Sao Paulo, Brazil. STUDY DESIGN: Cross-sectional survey. METHODS:
      The study used a two-stage cluster sampling survey design. Data were collected on
      a probabilistic sample of nightclub patrons. Overall, 2422 patrons were
      interviewed at the entrance of 31 nightclubs. Latent class analysis (LCA) was
      used to identify risk behavior profiles with an emphasis on risky driving,
      fights, alcoholic blackouts, and harm and unsafe sex. RESULTS: A 3-class LCA
      model was selected, with classes consisting of low (43%), medium (33%), and high
      (24%) risk patrons. Compared to patrons in the low-risk class, patrons in the
      medium- and high-risk classes were more likely to be men (odds ratio [OR] = 2.2,
      95% confidence interval {CI} [1.2-4.0] and OR = 3.2, 95% CI [1.8-5.8],
      respectively), to have engaged in binge drinking during the last year (OR = 15.0,
      95% CI [7.2-31.3] and OR = 14.3, 95% CI [9.4-21.8]), to be in the highest
      socioeconomic stratum (OR = 2.6, 95% CI [1.3-5.1] and OR = 2.0, 95% CI [1.2-3.5])
      and to have been interviewed at a hip-hop music nightclub (OR = 2.8, 95% CI [1.1
      6.8] and OR = 3.7, 95% CI [1.5-9.1]). CONCLUSIONS: Risk behaviors were not
      equally distributed among nightclubs. Individual- and environmental-level
      characteristics are associated with higher risk. Alcohol harm reduction, such as
      the implementation of a responsible drinking service, should be implemented in
      Sao Paulo nightclubs.

PMID- 29331773
TI  - Impact of co-exposure of aldrin and titanium dioxide nanoparticles at biochemical
      and molecular levels in Zebrafish.
AB  - Aldrin (ALD), a persistent-organic-pollutant (POP), an organochlorine-cyclodiene
      pesticide is highly toxic in nature. Titanium dioxide nanoparticles (TNP) are
      widely used for various industrial applications. Despite the remarkable research
      on pesticide toxicity, the work with impact of nanoparticles on POP has been
      dealt with marginally. Chemicals co-exist in the environment and exhibit
      interactive effects. An investigation was carried out to evaluate the individual
      and combined effects of ALD (6 ppm) and TNP (60 ppm) exposure at sub-lethal
      concentration for 24 h in zebrafish. Significant reversal of lipid peroxidation
      level in liver and brain tissues and restoration in enhanced catalase activity in
      all examined tissues were observed in combined group. For other parameters,
      combined exposure of ALD and TNP does not show significant reversal action on ALD
      toxicity. Further studies are inline to understand combined effects of both to
      achieve significant reversal of ALD toxicity by TNP nanoparticles with threshold
      concentration of aldrin.

PMID- 29331774
TI  - The synergy of Vitamin C with decitabine activates TET2 in leukemic cells and
      significantly improves overall survival in elderly patients with acute myeloid
      leukemia.
AB  - BACKGROUND: Decitabine is widely used in the treatment of acute myeloid leukemia
      (AML) in elderly patients. Low-dose Vitamin C has also been indicated to induce
      DNA demethylation at the cellular level. However, little is known whether low
      dose Vitamin C has a synergistic effect with decitabine in clinic. METHODS: The
      effect of combined low-dose Vitamin C and decitabine on cell proliferation, the
      cell cycle, apoptosis and the expression level and activity of TET2 was
      investigated in HL60 and NB4 human leukemic cells. Additionally, we analyzed the
      clinical outcomes of 73 elderly AML patients who received A-DCAG (intravenous
      Vitamin C [IVC] plus DCAG [n = 39]) or DCAG (n = 34) treatment. RESULTS: We found
      that low-dose Vitamin C and decitabine has a synergistic efficacy on
      proliferation, apoptosis, TET2 expression and activity, compared to drug-alone
      treatment in HL60 and NB4 cell lines in vitro. In clinic, feasibility and safety
      evaluations revealed that patients who received A-DCAG regimen have a higher
      complete remission (CR) rate than those who received the DCAG regimen (79.92% vs.
      44.11%; P = 0.004) after one cycle of chemotherapy. The median overall survival
      (OS) was better in the A-DCAG group compared with the DCAG group (15.3 months vs.
      9.3 months, P = 0.039). Patients with adverse cytogenetics did benefit from CR.
      There was no clinically significant additional toxicity observed with the
      addition of IVC. CONCLUSION: On the basis of these results, the addition of IVC
      at low doses to DCAG appeared to improve CR and prolong OS, compared with DCAG,
      in elderly patients with AML.

PMID- 29331775
TI  - Experience of lecturers with simulation training in midwifery education in
      Slovakia.
AB  - The simulation training in midwifery has a long tradition. It is aimed at
      acquiring basic and advanced practical skills such as performing a certain number
      of births, episiotomy and subsequent suture, assisting during breech birth etc.
      Midwifery education is currently based on the requirements of the Directives of
      the European Union exactly specifying number of performed practical procedures
      and approaches (World Health Organisation (WHO) Europe, 2009). The aim of this
      paper is to draw attention to the experience with the simulation training from
      the teacher's point of view in the study program Midwifery in Slovakia. The
      authors describe the locations for training of midwifery skills, training of
      basic and advanced midwifery skills using simulation, the types of simulators
      available and used and training approaches. They outline the advantages and
      disadvantages of using obstetric simulators based on their own experience.

PMID- 29331776
TI  - Low-cost screen-printed electrodes based on electrochemically reduced graphene
      oxide-carbon black nanocomposites for dopamine, epinephrine and paracetamol
      detection.
AB  - A green approach for the preparation of carbon black (CB) and electrochemically
      reduced graphene oxide composite (ERGO) is described based on screen printed
      carbon electrodes (SPCEs) fabricated on poly(ethylene terephthalate) (PET) as
      electrochemical sensors. This approach leads to a heterogeneous hydrophilic
      surface with high concentration of defect sites according to scanning electron
      microscopy, contact angle and Raman spectroscopy measurements. The SPCE/CB-ERGO
      sensor was tested with dopamine (DA), epinephrine (EP) and paracetamol (PCM),
      exhibiting an enhanced electrocatalytic performance compared to the bare SPCE. It
      displayed a wider linear range, lower limit of detection and a remarkably higher
      analytical sensitivity, viz. 1.5, 0.13 and 0.028 A L mol-1 for DA, EP and PCM,
      respectively, being also capable of simultaneous determination of the three
      analytes. Such high performance is demonstration that SPCE/CB-ERGO may serve as
      generic platform for cost-effective flexible electrochemical sensors.

PMID- 29331777
TI  - Comparing the antifouling effects of activated carbon and TiO2 in ultrafiltration
      membrane development.
AB  - We use activated carbon (AC) and titanium oxide (TiO2) nanomaterials as the
      additives to prepare four polyvinylidene fluoride (PVDF) based ultrafiltration
      membranes by nonsolvent induced phase separation. The surface properties (pore
      size, porosity, hydrophilicity and roughness) of the membranes are characterized
      by scanning electron microscopy, water contact angle measurement, and atomic
      force microscopy. The chemical properties of the membranes are evaluated by
      Fourier transform infrared spectroscopy with attenuated total reflection and X
      ray diffraction. All these additives can improve the surface hydrophilicity and
      water permeation flux of the membrane. However, the addition of TiO2
      nanoparticles (20-30 nm) results in larger surface porosities and pore sizes,
      which causes more severe membrane fouling compared with the neat PVDF membrane.
      The PVDF-AC membrane exhibits excellent fouling resistance. Particularly, the
      irreversible fouling after blending AC into PVDF reduces dramatically from 40% to
      25%. The antifouling performance of the PVDF-AC membrane may result from the
      improved hydrophilicity and the favorable surface and structure properties of the
      membrane. To the best of our knowledge, this is the first demonstration of the
      antifouling function of AC in membrane preparation. This study suggests that AC
      could be a new type of nanomaterial for developing antifouling membranes.

PMID- 29331778
TI  - Synthesis of a novel narrow-band-gap iron(II,III) oxide/titania/silver silicate
      nanocomposite as a highly efficient and stable visible light-driven
      photocatalyst.
AB  - Ag6Si2O7, a visible light-driven photocatalyst, has attracted considerable
      attention owing to its enormous environmental remediation potential. In this
      work, a magnetic iron(II,III) oxide/titania/silver silicate (Fe3O4/TiO2/Ag6Si2O7)
      nanocomposite was synthesized by anchoring TiO2 and Ag6Si2O7 on the surface of
      Fe3O4 nanoparticles. The morphology, crystal structure, as well as the
      spectroscopic, magnetic, and photocurrent properties of the as-prepared
      Fe3O4/TiO2/Ag6Si2O7 nanocomposite were studied. Methylene blue (MB) was used for
      evaluating the photocatalytic performance under simulated visible light. The
      Brunauer-Emmett-Teller (BET) surface area, total pore volumes, and average pore
      diameter of the Fe3O4/TiO2/Ag6Si2O7 nanocomposite were calculated to be 33.077
      m2/g, 0.099 cm3/g, and 15.45 nm, respectively. The Fe3O4/TiO2/Ag6Si2O7
      photocatalyst showed a narrow-band-gap (1.38 eV) while exhibiting excellent
      photocatalytic performance with a photocurrent of 9.4 uA/cm2 under simulated
      visible light. Furthermore, the nanocomposites showed high resistance to
      degradation (i.e., more than 80%) after 5 reaction cycles and as a result of high
      saturation magnetization (25.51 emu/g), the spent material was easily separated
      upon application of a magnetic field. Meanwhile, the photogenerated holes (h+)
      and superoxide ions (O2-) were confirmed as the main active species. This novel
      photocatalyst is expected to provide a new insight into the design of
      photocatalysts with excellent recyclability, high performance, and good
      stability.

PMID- 29331779
TI  - Superior peroxidase mimetic activity of tungsten disulfide nanosheets/silver
      nanoclusters composite: Colorimetric, fluorometric and electrochemical studies.
AB  - Developing a novel peroxidase nano-mimetic is a challenging research topic in
      biosensing field. Herein, WS2 nanosheets (WS2 NS) decorated with silver
      nanoclusters (AgNCs) was introduced as a new nanocomposite with improved
      peroxidase mimetic behavior. WS2 NS/AgNCs nanocomposite was synthesized by simple
      chemical reduction of silver cations in the presence of WS2 NS. The enhanced
      catalytic activity of nanocomposite in chemical and electrochemical reduction of
      H2O2 was studied using colorimetry, fluorometry and electrochemical techniques.
      Attaching the AgNCs on the surface of WS2 NS effectively improved the catalytic
      activity of these nanosheets, which may be connected to the difference of the
      Fermi energy levels of coupled nanomaterial. The unequal Fermi levels cause
      charge separation between two phases creating highly active sites on the
      interface of coupled nanomaterial. Moreover, the new mimetic nanocomposite was
      applied for the analysis of glucose in blood, based on its enzymatic oxidation
      using glucose oxidase and then, on the measurement of produced H2O2 by sensitive
      fluorescence detection system. In optimum condition, a linear association was
      found between the generated fluorescence intensity and glucose logarithmic
      concentration in the range of 0.05-400 uM, and the limit of detection (3S/m) was
      21 nM.

PMID- 29331780
TI  - Application of octanohydroxamic acid for liquid-liquid extraction of manganese
      oxides and fabrication of supercapacitor electrodes.
AB  - MnO2 and Mn3O4 particles were prepared by wet chemical methods and efficiently
      dispersed and mixed with multiwalled carbon nanotubes (MWCNT) for the fabrication
      of composite MnO2-MWCNT and Mn3O4-MWCNT electrodes for electrochemical
      supercapacitors (ES). The problem of particle agglomeration was addressed by
      particle extraction through a liquid-liquid interface (PELLI) using
      octanohydroxamic acid (OHA) as a new extractor. OHA exhibited remarkable
      adsorption on particles due to a bidentate bonding mechanism. The use of OHA
      broadened the application of PELLI technology, because it allowed good extraction
      of particles from an aqueous phase at high pH. Moreover, OHA allowed efficient
      extraction by strong adsorption on particles not only at the liquid-liquid
      interface, but also in the bulk of an aqueous phase. Building on the advantages
      offered by the PELLI method and OHA as an extractor we found that Mn3O4-MWCNT
      electrodes exhibited a remarkably high capacitance of 4.2F cm-2. Another major
      finding was that capacitance of Mn3O4-MWCNT electrodes was higher than that of
      MnO2-MWCNT electrodes at active mass of 33 mg cm-2. This finding showed
      processing advantages of PELLI and paved the way for applications of novel
      colloidal and surface modification strategies for the development of advanced ES.
      A conceptually new approach has been proposed based on the use of hydroxamic
      acids as capping agents for synthesis and extractor molecules for PELLI.

PMID- 29331781
TI  - A step-wise self-assembly approach in preparation of multi-responsive
      poly(styrene-co-methyl methacrylate) nanoparticles containing spiropyran.
AB  - HYPOTHESIS: Surfactant-free emulsion polymerization has become favorable due to
      circumventing instability issues reasonably. Incorporation of an appropriate
      hydrophilic macroRAFT, could provide controlled in-situ self-assembly via
      copolymerization with hydrophobic monomers into polymer particles. So far, this
      approach has mostly been studied in dispersion systems and further studies are
      needed in emulsions. Beside the corresponding mechanistic studies, the prepared
      latex particles would potentially exhibit smart behaviors by choosing stimuli
      responsive monomers. EXPERIMENTS: Poly(styrene-co-methyl methacrylate) latexes
      were prepared by utilizing pH-responsive polydimethylaminoethyl methacrylate as
      the hydrophilic segment through polymerization induced self-assembly (PISA). A
      systematic study on the effect of MMA amount, role of smart spiropyran
      ethylacrylate (SPEA) comonomer and the synthesized macroRAFT for inducing
      efficient assembly has been performed comparatively for the first time. FINDINGS:
      SEM and DLS analyses showed the effect of MMA content on the obtaining of
      spherical particles with bimodal or monodisperse size distributions in both
      series of samples. Kinetic studies through conversion measurements along with GPC
      analysis revealed that the incorporation of MMA and SPEA strongly affected the
      efficiency of in-situ self-assembly, particle formation and RAFT-controllability
      on molecular weights. Ultimately, acido/basochromism, pH-responsivity and UV
      responsivity of the prepared latexes were verified and the results showed their
      facile and fast multi-responsivity.

PMID- 29331782
TI  - Stratification during evaporative assembly of multicomponent nanoparticle films.
AB  - HYPOTHESIS: Multicomponent coatings with layers comprising different
      functionalities are of interest for a variety of applications, including
      electronic devices, energy storage, and biomaterials. Rather than creating such a
      film using multiple deposition steps, we explore a single-step method to create
      such films by varying the particle Peclet numbers, Pe. Our hypothesis, based on
      recent theoretical descriptions of the stratification process, is that by varying
      particle size and evaporation rate such that Pe of large and small particles are
      above and below unity, we can create stratified films of polymeric and inorganic
      particles. EXPERIMENTS: We present AFM on the surface composition of films
      comprising poly(styrene) nanoparticles (diameter 25-90 nm) and silica
      nanoparticles (diameter 8-14 nm). Previous studies on films containing both
      inorganic and polymeric particles correspond to large Pe values (e.g., 120-460),
      while we utilize Pe ~ 0.3-4, enabling us to test theories that have been
      developed for different regimes of Pe. FINDINGS: We demonstrate evidence of
      stratification and effect of the Pe ratio, although our results agree only
      qualitatively with theory. Our results also provide validation of recent
      theoretical descriptions of the film drying process that predict different
      regimes for large-on-top and small-on-top stratification.

PMID- 29331783
TI  - Comparative study of novel in situ decorated porous chitosan-selenium scaffolds
      and porous chitosan-silver scaffolds towards antimicrobial wound dressing
      application.
AB  - Dermal defects caused by trauma or disease are challenging to treat due to
      difficult-to-treat infections that impair wound healing. Due to the widespread
      emergence of drug-resistant bacteria and dwindling discoveries of new
      antibiotics, there is currently an urgent need to introduce novel antimicrobials
      effective against antibiotic-resistant bacteria without causing damage to host
      tissues. As selenium (Se) and silver (Ag) are known for their antimicrobial
      properties, we investigated the separate loading of these materials into porous
      chitosan/PVA (CS) scaffolds through a simple in situ deposition method to create
      two distinct wound dressing materials (CS-Se and CS-Ag). Scaffolds with Se
      nanostructures and scaffolds containing Ag nanostructures were characterized and
      their activities against S. aureus - (a Gram-positive bacterium), E. coli - (a
      Gram-negative bacterium) and Methicillin-Resistant S. aureus (MRSA) - (a multi
      drug resistant bacterium) were compared. The release of Ag and Se in vitro was
      shown to depend strongly on the release medium used (deionised water, mammalian
      or bacterial culture media). Ag-loaded scaffolds showed a significant reduction
      in CFUs and cytotoxicity towards fibroblasts while Se-loaded scaffolds showed
      abilities to damage bacterial cell membrane and non-toxicity to fibroblast.
      Overall, in this study we have demonstrated simple, in situ immobilization porous
      CS scaffolds with either Se or Ag nanostructures which could be used to suit
      different wound healing applications.

PMID- 29331784
TI  - Degradation of dyes by peroxymonosulfate activated by ternary CoFeNi-layered
      double hydroxide: Catalytic performance, mechanism and kinetic modeling.
AB  - Ternary CoFeNi-layered double hydroxide (CoFeNi-LDH) was synthesized and
      initially applied to activate peroxymonosulfate (PMS) for the degradation of
      Congo red (CR) and Rhodamine B (RhB). The results show that the CoFeNi-LDH/PMS
      system can efficiently degrade nearly 100% of 20 mg/L CR or 20 mg/L RhB within 6-
      and 10-min reaction times, respectively. And the catalyst exhibits higher
      degradation efficiency on CR than on RhB under identical conditions, which is
      confirmed by electron clouds of the highest occupied molecular orbital (HOMO) and
      lowest unoccupied molecular orbital (LUMO) performed by DFT calculations.
      Quenching tests reveal that SO4- is the dominant active species participating in
      the degradation process. Mechanism investigation demonstrates that Co(II)-Co(III)
      Co(II) cycle is responsible for activating PMS to generate radicals for dyes
      degradation. A dynamic kinetic model is successfully developed to simulate the
      concentration profiles of CR and RhB degradation in CoFeNi-LDH/PMS system. The
      empirical second order rate constants between SO4- and CR (kSO4-/CR), HO and CR
      (kOH/CR), SO4- and RhB (kSO4-/RhB), HO and RhB (kHO/RhB) are determined to be
      2.47 * 107, 3.44 * 106, 8.39 * 106 and 2.62 * 107 M-1s-1, respectively. In
      addition, toxic assessment using ECOSAR program suggests that the overall
      toxicity of CR and RhB decreased after treatment with CoFeNi-LDH/PMS system.
      Repeating tests and application of CoFeNi-LDH in different water sources give us
      adequate confidence that the as-synthesized CoFeNi-LDH is favorable for the
      purification of dye-contaminanted waters in practical.

PMID- 29331785
TI  - Causal nature of neighborhood deprivation on individual risk of coronary heart
      disease or ischemic stroke: A prospective national Swedish co-relative control
      study in men and women.
AB  - We studied the association between neighborhood socioeconomic status (SES) and
      incidence of coronary heart disease (CHD) or ischemic stroke in the total
      population and in full- and half-siblings to determine whether these associations
      are causal or a result from familial confounding. Data were retrieved from
      nationwide Swedish registers containing individual clinical data linked to
      neighborhood of residence. After adjustment for individual SES, the association
      between neighborhood SES and CHD showed no decrease with increasing genetic
      resemblance, particularly in women. This indicates that the association between
      neighborhood SES and CHD incidence is partially causal among women, which
      represents a novel finding.

PMID- 29331786
TI  - The meaning of community in diverse neighborhoods: Stratification of influence
      and mental health.
AB  - As the United States diversifies, individuals are increasingly encountering and
      managing racial and ethnic difference in their neighboring relationships, thus
      challenging the "cultural" basis for consensus on the local meaning of community.
      This mixed-methods study considers the ways in which sense of community relates
      to mental health in two longstanding racially- and socioeconomically-diverse
      neighborhoods. I ask how social resources are distributed within diverse
      neighborhoods, integrating survey (N = 243) and interview (N = 60) data to make
      observations about both the existence and nature of relationships among the
      unique dimensions of sense of community and mental health. Findings indicate that
      the influence dimension of sense of community is particularly vital for mental
      health, and that whites and homeowners perceive and utilize influence more than
      other residents. I use residents' narratives about their experiences to interpret
      how influence may relate to mental health and elaborate the ways in which people
      of color, renters, and individuals with long tenure comprehend their lack of
      influence in diverse neighborhoods.

PMID- 29331787
TI  - Val66Met functional polymorphism and serum protein level of brain-derived
      neurotrophic factor (BDNF) in acute episode of schizophrenia and depression.
AB  - BACKGROUND: Brain-derived neurotrophic factor (BDNF) influences neuron
      differentiation during development as well as the synaptic plasticity and neuron
      survival in adulthood. BDNF has been implicated in the pathogenesis of
      schizophrenia and depression. Val66Met polymorphism and BDNF serum level are
      potential biomarkers in neuropsychiatric disorders. The aim of this study was to
      determine the effect of BDNF gene Val66Met functional polymorphism on serum BDNF
      concentration in patients with schizophrenia, during depression episode and in
      healthy control group. METHODS: 183 participants were recruited (61 patients with
      depressive episode, 56 females with schizophrenia, 66 healthy controls) from
      Polish population. Serum BDNF levels were measured using ELISA method. Val66Met
      polymorphism was genotyped using PCR- RFLP method. RESULTS: Serum BDNF levels
      were not associated with Val66Met polymorphism in either of the groups. A
      significant increase of BDNF level in schizophrenia (p = 0.0005) and depression
      (p = 0.026) comparing to the control group has been observed. CONCLUSIONS: Our
      results suggest that the functional Val66Met BDNF polymorphism is not associated
      with BDNF serum levels, which is in line with previous findings. Replication
      studies on larger groups are needed.

PMID- 29331788
TI  - Curcumin inhibits cardiac hypertrophy and improves cardiovascular function via
      enhanced Na+/Ca2+ exchanger expression after transverse abdominal aortic
      constriction in rats.
AB  - BACKGROUND: This study tested the hypothesis that inhibition of cardiac
      hypertrophy and preservation of cardiac/endothelial function by the natural
      yellow pigment curcumin are associated with upregulated expression of Na+/Ca2+
      exchanger (NCX) after transverse aortic constriction (TAC). METHODS: Male Wistar
      rats were subjected to TAC for 10 weeks and curcumin (50 mg/kg/day) was fed by
      gastric gavage during TAC. Expression of NCX and endothelial nitric oxide
      synthase (eNOS) was analyzed by Western blot and immunohistochemistry. RESULTS:
      Compared with the animals in the TAC group, curcumin significantly increased the
      survival rate and reduced the ratio of heart or left ventricle (LV) to body
      weight and the cross sectional area of cardiomyocytes. In coincidence with
      improved LV systolic pressure and reduced LV end-diastolic pressure, curcumin
      significantly reduced LV end-systolic and diastolic diameter/dimension, and
      enhanced LV ejection fraction and LV fractional shortening as measured by
      echocardiography. Furthermore, endothelium-dependent relaxation of aortic rings
      in response to acetylcholine was significantly improved by curcumin. Along with
      these modifications, the expression and localization of NCX and eNOS in the
      myocardium and vascular endothelium were significantly upregulated by curcumin.
      The protective effect of curcumin on endothelium-dependent relaxation was partly
      blocked by pretreatment with the NCX inhibitor, KB-R7943. CONCLUSIONS: These
      results demonstrate that inhibition of cardiac hypertrophy, improvement of
      cardiac systolic/diastolic function and preservation of vascular endothelium by
      curcumin might be associated with upregulated NCX expression level in response to
      increased afterload.

PMID- 29331789
TI  - Anticonvulsant activities of alpha-asaronol ((E)-3'-hydroxyasarone), an active
      constituent derived from alpha-asarone.
AB  - BACKGROUND: Epilepsy is one of chronic neurological disorders that affects 0.5
      1.0% of the world's population during their lifetime. There is a still
      significant need to develop novel anticonvulsant drugs that possess superior
      efficacy, broad spectrum of activities and good safety profile. METHODS: alpha
      Asaronol and two current antiseizure drugs (alpha-asarone and carbamazepine
      (CBZ)) were assessed by in vivo anticonvulsant screening with the three most
      employed standard animal seizure models, including maximal electroshock seizure
      (MES), subcutaneous injection-pentylenetetrazole (PTZ)-induced seizures and 3
      mercaptopropionic acid (3-MP)-induced seizures in mice. Considering drug safety
      evaluation, acute neurotoxicity was assessed with minimal motor impairment
      screening determined in the rotarod test, and acute toxicity was also detected in
      mice. RESULTS: In our results, alpha-asaronol displayed a broad spectrum of
      anticonvulsant activity (ACA) and showed better protective indexes (PI = 11.11 in
      MES, PI = 8.68 in PTZ) and lower acute toxicity (LD50 = 2940 mg/kg) than its
      metabolic parent compound (alpha-asarone). Additionally, alpha-asaronol displayed
      a prominent anticonvulsant profile with ED50 values of 62.02 mg/kg in the MES and
      79.45 mg/kg in the sc-PTZ screen as compared with stiripentol of ED50 of 240
      mg/kg and 115 mg/kg in the relevant test, respectively. CONCLUSION: The results
      of the present study revealed alpha-asaronol can be developed as a novel
      molecular in the search for safer and efficient anticonvulsants having
      neuroprotective effects as well as low toxicity. Meanwhile, the results also
      suggested that alpha-asaronol has great potential to develop into another new
      aromatic allylic alcohols type anticonvulsant drug for add-on therapy of Dravet's
      syndrome.

PMID- 29331790
TI  - C-Phycocyanin: Cellular targets, mechanisms of action and multi drug resistance
      in cancer.
AB  - C-Phycocyanin (C-PC) has been shown to be promising in cancer treatment; however,
      although several articles detailing this have been published, its main mechanisms
      of action and its cellular targets have not yet been defined, nor has a detailed
      exploration been conducted of its role in the resistance of cancer cells to
      chemotherapy, rendering clinical use impossible. From our extensive examination
      of the literature, we have determined as our main hypothesis that C-PC has no one
      specific target, but rather acts on the membrane, cytoplasm, and nucleus with
      diverse mechanisms of action. We highlight the cell targets with which C-PC
      interacts (the MDR1 gene, cytoskeleton proteins, and COX-2 enzyme) that make it
      capable of killing cells resistant to chemotherapy. We also propose future
      analyses of the interaction between C-PC and drug extrusion proteins, such as
      ABCB1 and ABCC1, using in silico and in vitro studies.

PMID- 29331791
TI  - Magnesium sulfate reduces formalin-induced orofacial pain in rats with normal
      magnesium serum levels.
AB  - BACKGROUND: In humans, orofacial pain has a high prevalence and is often
      difficult to treat. Magnesium is an essential element in biological a system
      which controls the activity of many ion channels, neurotransmitters and enzymes.
      Magnesium produces an antinociceptive effect in neuropathic pain, while in
      inflammatory pain results are not consistent. We examined the effects of
      magnesium sulfate using the rat orofacial formalin test, a model of trigeminal
      pain. METHODS: Male Wistar rats were injected with 1.5% formalin into the
      perinasal area, and the total time spent in pain-related behavior (face rubbing)
      was quantified. We also spectrophotometrically determined the concentration of
      magnesium and creatine kinase activity in blood serum. RESULTS: Magnesium sulfate
      administered subcutaneously (0.005-45mg/kg) produced significant antinociception
      in the second phase of the orofacial formalin test in rats at physiological serum
      concentration of magnesium. The effect was not dose-dependent. The maximum
      antinociceptive effect of magnesium sulfate was about 50% and was achieved at
      doses of 15 and 45mg/kg. Magnesium did not affect increase the levels of serum
      creatine kinase activity. CONCLUSIONS: Preemptive systemic administration of
      magnesium sulfate as the only drug can be used to prevent inflammatory pain in
      the orofacial region. Its analgesic effect is not associated with magnesium
      deficiency.

PMID- 29331792
TI  - Candesartan, angiotensin II type 1 receptor blocker is able to relieve age
      related cognitive impairment.
AB  - BACKGROUND: Candesartan is one of the standard antihypertensive drug belonging to
      AT1R angiotensin receptor blockers (ARBs) group. Beneficial effects of this drug
      in the treatment of hypertension are well recognized. In this study we tested a
      hypothesis that candesartan could alleviate age-related memory decline. METHODS:
      Aged and young rats have been treated with candesartan (0.1mg kg-1) for 21days
      and then underwent a battery of behavioral tests: for assessment of long-term
      memory (Passive avoidance test - PA), recognition memory (Object recognition test
      - OR), locomotor functions (Open field - OF) and anxiety behavior (Elevated plus
      maze - EPM). RESULTS: Aged rats (2-years-old) displayed clear declining tendency
      in the retrieval of passive avoidance behavior showing thus increased forgetting.
      Prolonged administration of candesartan significantly (p<0.01) reversed this
      phenomenon causing recall measured as the avoidance latency, and surprisingly
      also showed the tendency to recall deterioration observed in the young rats. More
      optimistic results were achieved in the OR, where candesartan significantly
      improved recognition memory (p<0.001) of aged rats who performed even better than
      the young ones (p<0.05). CONCLUSIONS: It appears that candesartan potently
      abolishes some kinds of aging-induced memory impairments and cognitive declines
      in aged rats, but in some circumstances it may even could increase the damage of
      memory. It seems that the use of sartans in the treatment of hypertension for
      patients with associated cognitive impairment, or for people in risk groups for
      such disorders can be an interesting alternative.

PMID- 29331793
TI  - Moderate-dose simvastatin therapy potentiates the effect of vitamin D on thyroid
      autoimmunity in levothyroxine-treated women with Hashimoto's thyroiditis and
      vitamin D insufficiency.
AB  - BACKGROUND: Vitamin D preparations reduce titers of thyroid antibodies in women
      with autoimmune thyroiditis. The same effect was induced by high-dose, but not
      moderate-dose-, statin therapy. No previous study has investigated the impact of
      concomitant treatment with a statin and vitamin D on thyroid autoimmunity.
      METHODS: The study included three matched groups of women with Hashimoto's
      thyroiditis and low vitamin D status. Groups B (n=19) and C (n=20) were treated
      with vitamin D (2000 IU daily). Because of coexistent hypercholesterolemia,
      groups A (n=18) and B received simvastatin (40mg daily). Plasma lipids, serum
      levels of thyrotropin, free thyroid hormones and 25-hydroxyvitamin D, as well as
      titers of thyroid peroxidase and thyroglobulin antibodies were measured at the
      beginning of the study and 6 months later. RESULTS: At baseline, 25
      hydroxyvitamin D levels inversely correlated with titers of thyroid antibodies.
      In groups A and B, simvastatin reduced plasma levels of total and LDL
      cholesterol. Simvastatin produced no effect on thyroid antibody titers. Vitamin D
      decreased titers of thyroid peroxidase antibodies, as well as tended to decrease
      titers of thyroglobulin antibodies. Simvastatin-vitamin D combination therapy
      reduced serum titers of thyroid peroxidase and thyroglobulin antibodies and this
      effect was stronger than the effect of simvastatin and vitamin D administered
      alone. Treatment-induced changes in thyroid antibody titers correlated with
      baseline antibody titers, baseline levels of 25-hydroxyvitamin and treatment
      induced changes in 25-hydroxyvitamin. CONCLUSIONS: The obtained results indicate
      that simvastatin may potentiate the impact of vitamin D on thyroid autoimmunity
      in vitamin D-deficient women with Hashimoto's thyroiditis.

PMID- 29331794
TI  - Melatonin suppresses eosinophils and Th17 cells in hamsters treated with a
      combination of human liver fluke infection and a chemical carcinogen.
AB  - BACKGROUND: The combination of Opisthorchis viverrini (OV) infection and chemical
      carcinogen induces cholangiocarcinoma (CCA) in hamsters via inflammation-mediated
      mechanisms. Thus, suppression of inflammatory cells at the initial stages of CCA
      development would be of benefit. We aimed to investigate whether IL-17-producing
      CD4+ T cells (Th17) and CD4+ Foxp3+ T cells (Treg) are involved in the early
      stages of CCA genesis and can be targeted for suppression by melatonin. METHODS:
      Inflammation, an initial stage of CCA development, was induced in hamsters by a
      combination of O. viverrini infection and N-nitrosodimethylamine (NDMA)
      administration. Melatonin (50mg/kg) was additionally administered to one group
      for the 30days of the experiment. Liver tissue-resident T cells were investigated
      using immunostaining, western blotting, and real-time PCR. RESULTS: OV+NDMA
      induced CCA tissues showed significantly higher numbers of inflammatory cells,
      especially eosinophils, bile duct proliferation and IL-17+ cell infiltration
      compared to normal livers. Expression of Foxp3 was localized in the bile duct
      epithelial cells, and especially in the bile duct hyperplasia. Accumulation of
      CD4+ and IL-17+ cells and intense staining of the Foxp3+ marker were consistent
      with their protein levels. Infiltration of IL-17+ inflammatory cells and Foxp3+
      cells, as well as increases in their transcription expression levels, were
      significantly lower in the melatonin-treated group. In contrast, increased CD4+
      cell infiltration and TNF-alpha expression were also observed through melatonin
      treatment. CONCLUSION: Melatonin exerts an immunomodulatory effect, suppressing
      eosinophils and Th17 cells and expression of Foxp3, but enhancing CD4+ cells and
      TNF-alpha. This suggests that melatonin may be used for CCA chemoprevention.

PMID- 29331795
TI  - Development and validation of an UHPLC-MS/MS approach for simultaneous
      quantification of five bioactive saponins in rat plasma: Application to a
      comparative pharmacokinetic study of aqueous extracts of raw and salt-processed
      Achyranthes bidentata.
AB  - A simple, accurate and sensitive ultra high-performance liquid chromatography
      tandem mass spectrometry approach was established for the simultaneous
      determination of beta-ecdysterone, 25S-inokosterone, ginsenoside Ro,
      chikusetsusaponin IV and chikusetsusaponin IVa in rat plasma after oral
      administration of raw and salt-processed Achyranthes bidentata extract. The
      saponins were completely separated on a Waters BEH C18 UHPLC column by using
      acetonitrile/0.1% formic acid-water as mobile phases. The mass analysis was
      performed in a triple quadrupole mass spectrometer using multiple reaction
      monitoring (MRM) with negative scan mode. The sample preparations for protein
      removal were accomplished using a simple acetonitrile precipitation method. The
      calibration curves displayed good linearity (r2 > 0.9998) with the concentration
      ranges of 24.4-6100 ng mL-1, 25.6-6400 ng mL-1, 20.4-8500 ng mL-1, 21.6-5400 ng
      mL-1, 21.6-6100 ng mL-1 for the five saponins, respectively. The intra-day and
      inter-day precisions (RSD) of the five saponins were less than 3.95% and the bias
      of the accuracies ranged from -4.50% to 4.84%. The extraction recoveries of the
      five saponins ranged from 95.2% to 104.8% and the matrix effects were
      satisfactory. In comparison with the raw group, the parameters of Cmax and AUC0-t
      of beta-ecdysterone, 25S-inokosterone, ginsenoside Ro, and chikusetsusaponin IVa
      elevated remarkably (p < 0.05) after oral delivery of the extract of salt
      processed Achyranthes bidentata, which revealed that salt-processing could
      increase bioavailability of beta-ecdysterone, 25S-inokosterone, ginsenoside Ro
      and chikusetsusaponin IVa.

PMID- 29331796
TI  - Determination of meropenem in endotracheal tubes by in-tube solid phase
      microextraction coupled to capillary liquid chromatography with diode array
      detection.
AB  - Meropenem is a widely used antimicrobial for the treatment of infections
      associated with the use of invasive medical devices in intensive care unit
      patients. These treatments are not always effective, in fact, in-vitro studies
      have demonstrated the difficulty of antimicrobials to penetrate into the biofilm,
      however in-vivo studies of the effect of these compounds is a trend, mostly
      because of the complexity of pulmonary samples extracted from ETTs. Therefore,
      the objective of this study was to evaluate in-tube solid phase microextraction
      (in-tube SPME) coupled to capillary liquid chromatography (CapLC) with DAD to
      determine meropenem in ETTs in order to estimate the penetration capability into
      the biofilm. Firstly, different parameter affecting in-tube SPME, such as
      processed sample volume, capillary length, flow and capillary coating were
      studied. The best analytical response was achieved by processing 500 MUL of
      standards/samples at 9 MUL/seg with a 60-cm capillary column coated with 35%
      diphenyl 65%-polydimethylsiloxane. Under these conditions, the analytical
      performance of in-tube SPME-CapLC-DAD, using acetonitrile-water in gradient mode
      as mobile phase, showed satisfactory results for estimation of meropenem in terms
      of sensitivity (LOD = 3 MUg/L) and precision (RSD < 10%). Once the experimental
      conditions were stablished for in-tube SPME, the extraction of meropenem from the
      ETTs was studied. Liquid extraction, vortex-assisted liquid extraction (VALE) and
      ultrasound-extraction (UAE) extraction were tested. The results indicated that
      meropenem could be quantitatively extracted (91 +/- 6%) from ETTs, for its
      subsequent determination by in-tube SPME-CapLC-DAD using water as extraction
      solvent and 1 min as extraction time. Finally, samples from ETTs used for
      critically ill patients with different antimicrobial treatments were analysed
      with successful results.

PMID- 29331797
TI  - Application of polyacrylamide gel as a new membrane in electromembrane extraction
      for the quantification of basic drugs in breast milk and wastewater samples.
AB  - Introducing new membranes with green chemistry approach seems to be a great
      challenge for the development of a practical method in separation science. In
      this regard, for the first time, polyacrylamide gel as a new membrane in
      electromembrane extraction (EME) was used for the extraction of three model basic
      drugs (pseudoephedrine (PSE), lidocaine (LID), and propranolol (PRO)), followed
      by HPLC-UV. In comparison with conventional EME, in this method neither organic
      solvent nor carrier agents were used for extraction of mentioned drugs. Different
      variables for fabrication of polyacrylamide gel and extraction process were
      evaluated. Polyacrylamide gel (containing 12% (w/v) acrylamide, and 3.0% (w/w)
      bisacrylamide) with 2 mm thickness at pH = 1.5 was fabricated as membrane. The
      drugs were extracted from aqueous samples, through a polyacrylamide gel membrane,
      to an aqueous acceptor phase on membrane. Under the optimized extraction
      conditions (Voltage: 85 V, extraction time: 28 min, acceptor phase's pH: 4.0, and
      donor phase's pH: 7.0) limits of quantification and detection were in the ranges
      of 1.0-20.0 ng mL-1 and 0.3-6.0 ng mL-1, respectively. Applying the proposed
      method to determine and quantify intended drugs in breast milk, and wastewater
      samples have revealed acceptable results.

PMID- 29331798
TI  - Engaging students in a community of learning: Renegotiating the learning
      environment.
AB  - Promoting student engagement in a student led environment can be challenging.
      This article reports on the process of design, implementation and evaluation of a
      student led learning approach in a small group tutorial environment in a three
      year Bachelor of Nursing program at an Australian university. The research
      employed three phases of data collection. The first phase explored student
      perceptions of learning and engagement in tutorials. The results informed the
      development of a web based learning resource. Phase two centred on implementation
      of a community of learning approach where students were supported to lead
      tutorial learning with peers. The final phase constituted an evaluation of the
      new approach. Findings suggest that students have the capacity to lead and engage
      in a community of learning and to assume greater ownership and responsibility
      where scaffolding is provided. Nonetheless, an ongoing whole of course approach
      to pedagogical change would better support this form of teaching and learning
      innovation.

PMID- 29331799
TI  - The deepwater horizon oil spill coast guard cohort study: A cross-sectional study
      of acute respiratory health symptoms.
AB  - INTRODUCTION: Over 8500 United States Coast Guard (USCG) personnel were deployed
      in response to the Deepwater Horizon (DWH) oil spill; however, human respiratory
      effects as a result of spill-related exposures are relatively unknown. METHODS:
      USCG personnel who responded to the DWH oil spill were queried via survey on
      exposures to crude oil and oil dispersant, and acute respiratory symptoms
      experienced during deployment. Adjusted log binomial regressions were used to
      calculate prevalence ratios (PRs) and 95% confidence intervals (CI),
      investigating the associations between oil spill exposures and respiratory
      symptoms. RESULTS: 4855 USCG personnel completed the survey. More than half
      (54.6%) and almost one-fourth (22.0%) of responders were exposed to crude oil and
      oil dispersants, respectively. Coughing was the most prevalent symptom (19.4%),
      followed by shortness of breath (5.5%), and wheezing (3.6%). Adjusted analyses
      showed an exposure-response relationship between increasing deployment duration
      and likelihood of coughing, shortness of breath, and wheezing in the pre-capping
      period. A similar pattern was observed in the post-capping period for coughing
      and wheezing. Adjusted analyses revealed increased PRs for coughing (PR=1.92),
      shortness of breath (PR=2.60), and wheezing (PR=2.68) for any oil exposure.
      Increasing frequency of inhalation of oil was associated with increased
      likelihood of all three respiratory symptoms. A similar pattern was observed for
      contact with oil dispersants for coughing and shortness of breath. The
      combination of both oil and oil dispersants presented associations that were much
      greater in magnitude than oil alone for coughing (PR=2.72), shortness of breath
      (PR=4.65), and wheezing (PR=5.06). CONCLUSIONS: Results from the present study
      suggested strong relationships between oil and oil dispersant exposures and acute
      respiratory symptoms among disaster responders. Future prospective studies will
      be needed to confirm these findings.

PMID- 29331800
TI  - Nucleus accumbens mu opioid receptors regulate context-specific social
      preferences in the juvenile rat.
AB  - The MU opioid receptor (MOR) in the nucleus accumbens (NAc) is involved in
      assigning pleasurable, or hedonic value to rewarding stimuli. Importantly, the
      hedonic value of a given rewarding stimulus likely depends on an individual's
      current motivational state. Here, we examined the involvement of MORs in the
      motivation to interact with a novel or a familiar (cage mate) conspecific in
      juvenile rats. First, we demonstrated that the selective MOR antagonist CTAP
      administered into the NAc reduces social novelty preference of juvenile males, by
      decreasing the interaction time with the novel conspecific and increasing the
      interaction time with the cage mate. Next, we found that a 3-h separation period
      from the cage mate reduces social novelty preference in both juvenile males and
      females, which was primarily driven by an increase in interaction time with the
      cage mate. Last, we showed that MOR agonism (intracerebroventricularly or in the
      NAc) restored social novelty preference in juvenile males that did not show
      social novelty preference following social isolation. Taken together, these data
      support a model in which endogenous MOR activation in the NAc facilitates the
      relative hedonic value of novel over familiar social stimuli. Our results may
      implicate the MOR in neuropsychiatric disorders characterized by altered social
      motivation, such as major depression and autism spectrum disorder.

PMID- 29331802
TI  - Hair cortisol and work stress: Importance of workload and stress model (JDCS or
      ERI).
AB  - Hair cortisol concentrations (HCCs) are a potential physiological indicator of
      work related stress. However, studies that tested the relationship between HCC
      and self-reported stress in a work setting show mixed findings. This may be
      because few studies used worker samples that experience prolonged stress.
      Therefore, we compared a high workload sample (n = 81) and a normal workload
      sample (n = 91) and studied whether HCC was related to: (i) high job demands, low
      control, and low social support (JDCS model), and (ii) high effort, low reward,
      and high overcommitment (ERI model). Results showed that self-reported stress
      related to HCC only in the high workload sample and only for the variables of the
      ERI model. We found that HCC was higher when effort was high, reward low, and
      overcommitment high. An implication of this study is that a certain stress
      threshold may need to be reached to detect a relationship between self-reported
      stress and physiological measures such as HCC.

PMID- 29331801
TI  - Stressful life events, relationship stressors, and cortisol reactivity: The
      moderating role of suppression.
AB  - Stressful life events (SLEs) are exceedingly common and have been associated with
      a range of psychological disorders, perhaps through dysregulation in the
      hypothalamic-pituitary-adrenal (HPA) axis. The use of certain emotion regulation
      strategies in response to stress, such as expressive suppression and cognitive
      reappraisal, has additionally been linked to heightened HPA axis reactivity to
      acute stress. However, it is unclear how emotion regulation may interact with
      SLEs to affect HPA axis reactivity, particularly concerning relationship
      stressors (RSs). Using cross-sectional data from 117 men and 85 women aged 18-55
      years old (M = 39.9 +/- 10.7), we investigated whether trait use of suppression
      or reappraisal interacted with recent negatively perceived SLEs and relationship
      stressors to impact HPA axis response to an acute stressor. Separate area under
      the curve and linear mixed models revealed that trait suppression interacted with
      SLEs and RSs to predict cortisol response to stress, while reappraisal did not.
      Findings indicate higher trait expressive suppression may influence the cortisol
      response to acute stress after exposure to more recent stressful events,
      particularly when those stressful events include relationship stress.

PMID- 29331803
TI  - Caspases are key regulators of inflammatory and innate immune responses mediated
      by TLR3 in vivo.
AB  - Understanding the key regulators which impact the innate immune response during
      initial phases of tissue injury, can advance the use of therapeutic approaches
      which aim at attenuating inflammation and organ damage. Recognition of microbial
      components by TLRs, initiates the transcription of innate immune signal pathways,
      that induce the expression of key inflammatory mediators: cytokines, chemokines
      and adhesion molecules. Beside regulating apoptotic cell death, recent studies
      have revealed distinct roles for caspases in the optimal production of
      inflammatory cytokines and host defense against injurious infections. Whether
      caspases can play an immune regulatory role in vivo has not been sufficiently
      investigated. This study aims to explore whether the pan caspase inhibitor z-VAD
      fmk can control inflammation and cytokine production subsequent to challenging
      the innate immunity of the exocrine secretory tissues in vivo. Submandibular
      glands (SMGs) of the C57BL/6 mice were challenged with the TLR3 stimulant:
      polyinosinic-polycytidylic acid (poly (I:C)). Results obtained from the current
      study provide evidence that caspases can control immune responses downstream of
      TLR3 ligation. The present work proposes a novel mechanism that can prevent
      overactivation of the innate immunity, which typically leads to fatal immune
      disorders.

PMID- 29331804
TI  - Toll-like receptor 9 antagonist suppresses humoral immunity in experimental
      autoimmune myasthenia gravis.
AB  - Recent studies have demonstrated the important role of toll-like receptor 9
      (TLR9) signalling in autoimmune diseases, but its role in myasthenia gravis (MG)
      has not been fully established. We show herein that blocking TLR9 signalling via
      the suppressive oligodeoxynucleotide (ODN) H154 alleviated the symptoms of
      experimental autoimmune myasthenia gravis (EAMG). With the downregulation of
      dendritic cells (DCs), TLR9 interruption reduced follicular helper T cells (Tfh)
      and germinal centre (GC) B cells, leading to decreased antibody production. In
      addition, TLR9+ B cells as well as total B cells in the spleen were inhibited by
      H154. These findings highlight the critical role of TLR9 in EAMG and suggest that
      the inhibition of the TLR9 pathway might be a potential pharmacological strategy
      for the treatment of myasthenia gravis.

PMID- 29331805
TI  - Synthesis, characterization and anticancer activity in vitro and in vivo
      evaluation of an iridium (III) polypyridyl complex.
AB  - An iridium (III) complex [Ir(ppy)2(BDPIP)]PF6 (Ir-1) was reported to show high
      anticancer activity and may be used as a potent anticancer drug. In the current
      study, we designed and synthesized a novel iridium (III) complex and evaluated
      its potential inhibitory effect on the cancer cell growth in vitro and in vivo.
      This complex was found to display high cytotoxic activity in vitro and in vivo
      against A549 cell with a low IC50 value of 3.6 +/- 0.3 MUM and inhibiting
      percentage of tumor growth is 63.84% compared with the control. The complex also
      exhibited potencies superior to that of cisplatin toward A549 cell in vitro and
      in vivo. Further studies revealed that the complex can induce apoptosis and
      autophagy, enhance the ROS level, cause a decrease in the mitochondrial membrane
      potential and inhibit the cell invasion. Our findings indicated that the complex
      induced apoptosis in A549 through mitochondria dysfunction and PI3K/AKT/mTOR
      signaling pathways.

PMID- 29331806
TI  - Unifying in vitro and in vivo IVT mRNA expression discrepancies in skeletal
      muscle via mechanotransduction.
AB  - The translational efficiency of an in vitro transcribed (IVT) mRNA was measured
      upon delivery to primary skeletal muscle cells and to a mouse model system,
      towards the development of a predictive in vitro assay for the screening and
      validation of intramuscular mRNA-based vaccines. When IVT mRNA was delivered
      either naked or complexed with novel aminoglycoside-based delivery vehicles,
      significant differences in protein expression in vitro and in vivo were observed.
      We hypothesized that this previously anticipated discrepancy was due to
      differences in the mechanism of IVT mRNA endosomal entry and release following
      delivery. To address this, IVT mRNA was fluorescently labeled prior to delivery,
      to visualize its distribution. Colocalization with endosomal markers indicated
      that different entry pathways were utilized in vivo and in vitro, depending on
      the delivery vehicle, resulting in variations in protein expression levels. Since
      extracellular matrix stiffness (ECM) influences mRNA entry, trafficking and
      release, the effect of mechanotransduction on mRNA expression was investigated in
      vitro upon delivery of IVT mRNA alone, and complexed with delivery vehicles to
      skeletal muscle cells grown on ~10 kPa hydrogels. This in vitro hydrogel model
      more accurately recapitulated the results obtained in vivo upon IM injection,
      indicating that this approach may assist in the characterization of mRNA based
      vaccines.

PMID- 29331807
TI  - Clay nanoparticles for regenerative medicine and biomaterial design: A review of
      clay bioactivity.
AB  - Clay nanoparticles, composites and hydrogels are emerging as a new class of
      biomaterial with exciting potential for tissue engineering and regenerative
      medicine applications. Clay particles have been extensively explored in polymeric
      nanocomposites for self-assembly and enhanced mechanical properties as well as
      for their potential as drug delivery modifiers. In recent years, a cluster of
      studies have explored cellular interactions with clay nanoparticles alone or in
      combination with polymeric matrices. These pioneering studies have suggested new
      and unforeseen utility for certain clays as bioactive additives able to enhance
      cellular functions including adhesion, proliferation and differentiation, most
      notably for osteogenesis. This review examines the recent literature describing
      the potential effects of clay-based nanomaterials on cell function and examines
      the potential role of key clay physicochemical properties in influencing such
      interactions and their exciting possibilities for regenerative medicine.

PMID- 29331809
TI  - Environmental behavior of coated NMs: Physicochemical aspects and plant
      interactions.
AB  - The application of nanomaterials (NMs) depends on several characteristics,
      including polydispersity, shape, surface charge, and composition, among others.
      However, the specific surface properties of bare NMs induce aggregation, reducing
      their utilization. Thus, different surface coverages have been developed to avoid
      or minimize NMs aggregation, making them more stable for the envisioned
      applications. Carbon-based NMs are usually coated with metals, while metal-based
      NMs are coated with natural organic compounds including chitosan, dextran,
      alginate, or citric acid. On the other hand, the coating process is expected to
      modify the surface properties of the NMs; several coating agents add negative or
      positive charges to the particles, changing their interaction with the
      environment. In this review, we analyze the most recent literature about coating
      processes and the behavior of coated NMs in soil, water, and plants. In
      particular, the behavior of the most commercialized metal-based NMs, such as
      TiO2, ZnO, CeO2, CuO, Ag, and Au, and carbon-based NMs are discussed in this
      review. The available articles about the effects of coated NMs in plants are
      discussed. Up to now, there is no uniformity in the information to ensure that
      the surface coverage increases or decreases the effects of NMs in plants. While
      some parameters are increased, others are decreased. Since the data is
      contradictory in some cases, the available literature does not allow researchers
      to determine what concentrations benefit the plants. This review highlights
      current results and future perspectives on the study of the effects of coated NMs
      in the environment.

PMID- 29331810
TI  - Behavior of Cylindrospermopsis raciborskii during coagulation and sludge storage 
      higher potential risk of toxin release than Microcystis aeruginosa?
AB  - Owing to the global warming and its strong adaptability, Cylindrospermopsis
      raciborskii has spread world-wide. However, as one of toxic cyanobacteria in many
      drinking water sources, it has not been drawn proper consideration in drinking
      water treatment plants so far. The investigation aimed at unveiling the fate of
      C. raciborskii during polyaluminum ferric chloride (PAFC) coagulation and sludge
      storage, revealing its differences from Microcystis aeruginosa. Results showed
      that C. raciborskii cells were effectively removed intactly under optimum
      coagulation conditions, but PAFC at higher dosages (>10 mg/L) triggered
      additional cylindrospermopsins release. In sludge storage, coagulated C.
      raciborskii cells suffered severe oxidative damage, leading to significant
      cylindrospermopsins release after day 6. C. raciborskii manifested different
      behaviors from M. aeruginosa which cells didn't release much microcystins during
      coagulation and sludge storage. This was mostly due to their differences in
      physiology and morphology. In flocs, M. aeruginosa could be enveloped by
      coagulant which can protect cells against the nasty attack from outside, whereas
      C. raciborskii with long filaments was hard to be wrapped and prone to suffering
      oxidative damage. These results confirmed C. raciborskii had a higher risk of
      toxin release in water production process than M. aeruginosa, which should
      deserve more attention.

PMID- 29331808
TI  - Simultaneous inhibition of hedgehog signaling and tumor proliferation remodels
      stroma and enhances pancreatic cancer therapy.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers. It has
      an excessive desmoplastic stroma that can limit the intratumoral delivery of
      chemotherapy drugs, and protect tumor cells against radiotherapy. Therefore, both
      stromal and tumor compartments need to be addressed in order to effectively treat
      PDAC. We hereby co-deliver a sonic hedgehog inhibitor, cyclopamine (CPA), and a
      cytotoxic chemotherapy drug paclitaxel (PTX) with a polymeric micelle formulation
      (M-CPA/PTX). CPA can deplete the stroma-producing cancer-associated fibroblasts
      (CAFs), while PTX can inhibit tumor proliferation. Here we show that in
      clinically relevant PDAC models, M-CPA effectively modulates stroma by increasing
      microvessel density, alleviating hypoxia, reducing matrix stiffness while
      maintaining the tumor-restraining function of extracellular matrix. M-CPA/PTX
      also significantly extends animal survival by suppressing tumor growth and
      lowering the percentages of poorly to moderately differentiated tumor phenotypes.
      Our study suggests that using multifunctional nanoparticles to simultaneously
      target stromal and tumor compartments is a promising strategy for PDAC therapy.

PMID- 29331811
TI  - Volatile organic compounds (VOCs) removal in non-thermal plasma double dielectric
      barrier discharge reactor.
AB  - Non-thermal plasma (NTP) an emerging technology to treat volatile organic
      compounds (VOCs) present in unhygienic point source air streams. In present
      study, double dielectric barrier discharge (DDBD) reactors were used for the
      first time to evaluate the removal efficiency of VOCs mixture of different nature
      at constant experimental conditions (input power 16-65.8 W, VOCs mixture feeding
      rate 1-6 L/min, 100-101 ppm inlet concentration of individual VOC). Reactor A and
      B with discharge gap at 6 mm and 3 mm respectively, were used in current study.
      When treated at an input power of 53.7 W with gas feeding rate of 1 L/min in DDBD
      reactor A, removal efficiency of the VOCs were: tetrachloroethylene (100%),
      toluene (100%), trichloroethylene (100%), benzene (100%), ethyl acetate (100%)
      and carbon disulfide (88.30%); whereas in reactor B, the removal efficiency of
      all VOCs were 100%. Plasma-catalyst (Pt-Sn/Al2O3, BaTiO3 and HZSM-5) synergistic
      effect on VOCs removal efficiency was also investigated. Highest removal
      efficiency i.e 100% was observed for each compound with BaTiO3 and HZSM-5 at an
      input power 65.8 W. However, integrating NTP with BaTiO3 and HZSM-5 leads to
      enhanced removal performance of VOCs mixture with high activity, increase in
      energy efficiency and suppression of unwanted byproducts.

PMID- 29331812
TI  - Evidence of C--F-P and aromatic pi--F-P weak interactions in imidazolium ionic
      liquids and its consequences.
AB  - A simple change from alkyl group to alkene in side chain of imidazolium cation
      with same anion resulted in a drastic impact on physical properties (e.g.,
      melting point) from bmimPF6 IL to cmimPF6 IL. The underlying reasons have been
      elucidated by structural and interaction studies with the help of DSC, SCXRD,
      vibrational and multi-nuclear NMR spectroscopic techniques. Experiments reveal
      existence of new weak interactions involving the carbon and pi cloud of the
      imidazolium aromatic ring with fluoride of PF6 anion (i.e., C2--F-P and pi--F-P)
      in cmimPF6 but are absent in structurally similar prototype IL, bmimPF6. Though
      weak, these interactions helped to form ladder type supramolecular arrangement,
      resulting in quite high melting point for cmimPF6 IL compared to bmimPF6 IL.
      These findings emphasize that an IL system can behave uniquely because of the
      existence of uncommon weak interactions.

PMID- 29331813
TI  - Comparative study of the efficiency of computed univariate and multivariate
      methods for the estimation of the binary mixture of clotrimazole and
      dexamethasone using two different spectral regions.
AB  - Three methods of analysis are conducted that need computational procedures by the
      Matlab(r) software. The first is the univariate mean centering method which
      eliminates the interfering signal of the one component at a selected wave length
      leaving the amplitude measured to represent the component of interest only. The
      other two multivariate methods named PLS and PCR depend on a large number of
      variables that lead to extraction of the maximum amount of information required
      to determine the component of interest in the presence of the other. Good
      accurate and precise results are obtained from the three methods for determining
      clotrimazole in the linearity range 1-12 MUg/mL and 75-550 MUg/mL with
      dexamethasone acetate 2-20 MUg/mL in synthetic mixtures and pharmaceutical
      formulation using two different spectral regions 205-240 nm and 233-278 nm. The
      results obtained are compared statistically to each other and to the official
      methods.

PMID- 29331814
TI  - Characterization of sp3 bond content of carbon films deposited by high power gas
      injection magnetron sputtering method by UV and VIS Raman spectroscopy.
AB  - This paper presents the results of investigations of carbon films deposited by a
      modified version of the magnetron sputtering method - HiPGIMS (High Power Gas
      Injection Magnetron Sputtering). In this experiment, the magnetron system with
      inversely polarized electrodes (sputtered cathode at ground potential and
      positively biased, spatially separated anode) was used. This arrangement allowed
      us to conduct the experiment using voltages ranging from 1 to 2kV and a power
      supply system equipped with 25/50MUF capacitor battery. Carbon films were
      investigated by VIS/UV Raman spectroscopy. Sp3/sp2 bonding ratio was evaluated
      basing the elementary components of registered spectra. Our investigation showed
      that sp3 bond content increases with discharge power but up to specific value
      only. In extreme conditions of generating plasma impulses, we detected a reversed
      relation of the sp3/sp2 ratio. In our opinion, a energy of plasma pulse favors
      nucleation of a sp3 phase because of a relatively higher ionization state but in
      extreme cases the influence of energy is reversed.

PMID- 29331815
TI  - Chemometric simultaneous determination of Sofosbuvir and Ledipasvir in
      pharmaceutical dosage form.
AB  - Partial least squares (PLS), different families of continuous wavelet transform
      (CWT), and first derivative spectrophotometry (DS) techniques were studied for
      quantification of Sofosbuvir (SFB) and Ledipasvir (LDV) simultaneously without
      separation step. The components were dissolved in Acetonitrile and the spectral
      behaviors were evaluated in the range of 200 to 400nm. The ultraviolet (UV)
      absorbance of LDV exhibits no interferences between 300 and 400nm and it was
      decided to predict the LDV amount through the classic spectrophotometry (CS)
      method in this spectral region as well. Data matrix of concentrations and
      calibrated models were developed, and then by applying a validation set the
      accuracy and precision of each model were studied. Actual concentrations versus
      predicted concentrations plotted and good correlation coefficients by each method
      resulted. Pharmaceutical dosage form was quantified by developed methods and the
      results were compared with the High Performance Liquid Chromatography (HPLC)
      reference method. Analysis Of Variance (ANOVA) in 95% confidence level showed no
      significant differences among methods.

PMID- 29331816
TI  - New robust sensitive fluorescence spectroscopy coupled with PLSR for estimation
      of quercetin in Ziziphus mucronata and Ziziphus sativa.
AB  - Flavonoids are natural antioxidants derived from plants and commonly found in a
      variety of foods to sequester free radicals. Quercetin, belonging to flavonol
      subclass of flavonoids, has received considerable attention because of its wide
      uses as a nutritional supplement as well as a phytochemical remedy for a number
      of diseases. In the current study, quantification of quercetin was carried out in
      two medicinally important flavonoid rich plant Ziziphus mucronata and Ziziphus
      sativa. Emission spectroscopy was utilized as a new method coupled with Partial
      Least Squares Regression (PLSR) and the cross validation was done by UV-Visible
      spectroscopy. The results indicated the higher quercetin content in Z. mucronata
      (1.50+/-0.034%) than Z. sativa (1.21+/-0.052%), and were further verified through
      Folin-Ciocalteu Colorimetric method (Z. mucronata; 1.41+/-0.26% and Z. sativa;
      1.13+/-0.136%). In this study the sensitivity was explained in term of slope i.e.
      Slope=0.9973.

PMID- 29331817
TI  - Vapochromic behavior of MOF for selective sensing of ethanol.
AB  - A MOF material, Co3[Co(CN)6]2 nanoparticles has been prepared for the effective
      detection of ethanol in vapor phase. When exposed to ethanol vapor, the material
      was changed from pink to purple, which is easily observed by naked eyes directly.
      We propose that the ethanol response is due to ethanol molecules entering the
      pores of the solid, where they alter the coordination geometry, leading to
      conversion of their Co centers from octahedral to tetrahedral coordination.
      Significantly, the change is reversible, which make the material reusable without
      subjecting to dynamic vacuum or slightly warming.

PMID- 29331818
TI  - The effect of CaO/SiO2 molar ratio of CaO-Al2O3-SiO2 glasses on their structure
      and reactivity in alkali activated system.
AB  - The influence of CaO/SiO2 molar ratio of calcium aluminosilicate glasses on
      resulting structure and reactivity was investigated. Chemical compositions of
      glasses were chosen to mimic the composition of the fly ash and slag amorphous
      phase. Understanding the reactivity of these materials is of high importance
      allowing further development of the composite cements to limit the environmental
      footprint of cement industry. Fourier transform infrared spectroscopy (FTIR) and
      Raman spectroscopy were employed to examine the structure of glasses. Reactivity
      of the glasses was analyzed on paste samples after 1, 2, 7, 28 and 90days of
      curing by means of thermogravimetry (TGA), X-ray diffraction (XRD) and FTIR.
      Spectroscopic results emphasize dependence of the structure on the chemical
      composition of the glasses. The higher CaO/SiO2 the more depolymerized the glass
      network is, though there is no direct correlation with the reactivity.
      Significant differences in reactivity is observed primarily between the glasses
      of peraluminous (CaO/Al2O3<1) and percalcic region (CaO/Al2O3>1). Amongst the
      pastes made of glasses of percalcic region a higher degree of reaction at later
      ages is observed for the paste containing glass of lower CaO/SiO2 molar ratio.
      This is due to both degree of depolimerization and the nature of these glasses
      (pozzolanic and hydraulic materials). No difference of degree of reaction has
      been observed within the glasses of CaO/SiO2 lower than 1.

PMID- 29331819
TI  - New strategy for determination of anthocyanins, polyphenols and antioxidant
      capacity of Brassica oleracea liquid extract using infrared spectroscopies and
      multivariate regression.
AB  - A new method was developed to determine the antioxidant properties of red cabbage
      extract (Brassica oleracea) by mid (MID) and near (NIR) infrared spectroscopies
      and partial least squares (PLS) regression. A 70% (v/v) ethanolic extract of red
      cabbage was concentrated to 9 degrees  Brix and further diluted (12 to 100%) in
      water. The dilutions were used as external standards for the building of PLS
      models. For the first time, this strategy was applied for building multivariate
      regression models. Reference analyses and spectral data were obtained from
      diluted extracts. The determinate properties were total and monomeric
      anthocyanins, total polyphenols and antioxidant capacity by ABTS (2,2-azino-bis(3
      ethyl-benzothiazoline-6-sulfonate)) and DPPH (2,2-diphenyl-1-picrylhydrazyl)
      methods. Ordered predictors selection (OPS) and genetic algorithm (GA) were used
      for feature selection before PLS regression (PLS-1). In addition, a PLS-2
      regression was applied to all properties simultaneously. PLS-1 models provided
      more predictive models than did PLS-2 regression. PLS-OPS and PLS-GA models
      presented excellent prediction results with a correlation coefficient higher than
      0.98. However, the best models were obtained using PLS and variable selection
      with the OPS algorithm and the models based on NIR spectra were considered more
      predictive for all properties. Then, these models provided a simple, rapid and
      accurate method for determination of red cabbage extract antioxidant properties
      and its suitability for use in the food industry.

PMID- 29331820
TI  - Using vibrational molecular spectroscopy to reveal association of steam-flaking
      induced carbohydrates molecular structural changes with grain fractionation,
      biodigestion and biodegradation.
AB  - Advanced vibrational molecular spectroscopy has been developed as a rapid and non
      destructive tool to reveal intrinsic molecular structure conformation of
      biological tissues. However, this technique has not been used to systematically
      study flaking induced structure changes at a molecular level. The objective of
      this study was to use vibrational molecular spectroscopy to reveal association
      between steam flaking induced CHO molecular structural changes in relation to
      grain CHO fractionation, predicted CHO biodegradation and biodigestion in
      ruminant system. The Attenuate Total Reflectance Fourier-transform Vibrational
      Molecular Spectroscopy (ATR-Ft/VMS) at SRP Key Lab of Molecular Structure and
      Molecular Nutrition, Ministry of Agriculture Strategic Research Chair Program
      (SRP, University of Saskatchewan) was applied in this study. The fractionation,
      predicted biodegradation and biodigestion were evaluated using the Cornell Net
      Carbohydrate Protein System. The results show that: (1) The steam flaking induced
      significant changes in CHO subfractions, CHO biodegradation and biodigestion in
      ruminant system. There were significant differences between non-processed (raw)
      and steam flaked grain corn (P<.01); (2) The ATR-Ft/VMS molecular technique was
      able to detect the processing induced CHO molecular structure changes; (3)
      Induced CHO molecular structure spectral features are significantly correlated
      (P<.05) to CHO subfractions, CHO biodegradation and biodigestion and could be
      applied to potentially predict CHO biodegradation (R2=0.87, RSD=0.74, P<.01) and
      intestinal digestible undegraded CHO (R2=0.87, RSD=0.24, P<.01). In summary, the
      processing induced molecular CHO structure changes in grain corn could be
      revealed by the ATR-Ft/VMS vibrational molecular spectroscopy. These molecular
      structure changes in grain were potentially associated with CHO biodegradation
      and biodigestion.

PMID- 29331821
TI  - Influences of CdSe NCs on the photovoltaic parameters of BHJ organic solar cells.
AB  - In this study, the high quality CdSe nanocrystals (NCs) capped with stearic acid
      were synthesized in a solvent and then purified four times by using the
      precipitation and redissolution process. The average size of the synthesized CdSe
      NCs was determined ~3.0nm via transmission electron microscopy (TEM) measurement
      and their corresponding optical band edge energy was also calculated as ~2.1eV
      using ultraviolet-visible (UV-Vis) absorption spectroscopy. The bulk
      heterojunction (BHJ) hybrid solar cells based on a ternary system including P3HT,
      PCBM and CdSe NCs at different weight concentrations (0wt%, 0.1wt%, 0.5wt%, 1wt%
      and 2wt%) were fabricated by spin-casting process. The effect of the
      concentration of CdSe NCs on the photovoltaic parameters of these BHJ organic
      solar cells was investigated. The surface morphology of the photoactive layer
      modified by the incorporation of CdSe NCs into P3HT:PCBM matrix was observed with
      scanning electron microscopy (SEM). It was shown that when the concentration of
      CdSe NCs increases above 0.1wt% in this ternary system, the photovoltaic
      performance of the devices significantly decreases. The power conversion
      efficiency of the organic photovoltaic (OPV) device was enhanced ~20% by
      incorporating CdSe NCs with 0.1wt% with respect to those without CdSe NCs.

PMID- 29331822
TI  - Synthesis of UiO-66-OH zirconium metal-organic framework and its application for
      selective extraction and trace determination of thorium in water samples by
      spectrophotometry.
AB  - In this study, a zirconium-based metal-organic framework (Zr-MOF), named UiO-66
      OH, was synthesized by the solvo-thermal method and characterized by Fourier
      transform-infrared spectroscopy (FTIR), powder X-ray diffraction (PXRD), and
      scanning electron microscopy (SEM). This Zr-MOF was then employed as a sorbent
      for selective extraction and preconcentration of thorium ions after their
      complexation with 2-(2,4-dihydroxyphenyl)-3,5,7-trihydroxychromen-4-one (morin)
      from environmental water samples prior to its spectrophotometrical determination.
      The experimental parameters affecting extraction, such as pH of sample solution,
      amount of Zr-MOF, type and volume of eluting solvent, adsorption and desorption
      time, and concentration of complexing agent were evaluated and optimized. Under
      the optimized conditions, an enrichment factor of 250 was achieved. The limit of
      detection was calculated to be 0.35MUg.L-1 with a linear range between 10 and
      2000MUg.L-1of thorium. The maximum sorption capacity of MOF toward thorium was
      found to be 47.5mg.g-1. The proposed procedure was successfully applied to the
      analysis of real water samples.

PMID- 29331823
TI  - Pre-pregnancy maternal depressive symptoms and low birth weight and preterm birth
      outcomes: Assessment of adolescent background characteristics and birth outcomes
      in adulthood.
AB  - PURPOSE: In the United States and other countries of the world , high prevalence
      of pre-pregnancy depressive symptoms and depression during pregnancy is an
      important public health concern, as they are associated with low birth weight
      (LBW) and preterm birth (PTB) outcomes in adulthood. However, the relationships
      among pre-pregnancy depressive symptoms, low birth weight, preterm birth outcomes
      and household characteristics have not been well established. METHODS: The study
      used data from 7120 adolescent female participants in the National Longitudinal
      Study of Adolescent to Adult Health data from Waves I (1994-1995 in-school
      interview), II (1996 as in-home), III (2001-2002 as in-home interview), IV (2008
      as in-home interview) and Wave V is currently underway. The main outcomes were
      LBW and PTB. Maternal depressive symptoms were assessed with the Center for
      Epidemiologic Studies Depression scale (CES-D) using a cut-off point of 24 to
      indicate higher depressive symptoms . Odds ratios were used as an estimate of the
      relative risk using generalized estimating equations (GEE). RESULTS: In Wave I,
      prevalence of depressive symptoms among age groups 11-15 (54.1%) was higher than
      older adolescents (45.9%) were. With the exception of depressive symptoms
      reported in Wave II, respondents reporting depressive symptoms in Waves I and III
      had similar unadjusted rates of LBW or PTB infants in adulthood. Mothers
      reporting higher depressive symptoms in older adolescence (15-19 years) had
      elevated odds of LBW infants (3.58 [95% CI=1.81, 7.09]) in Wave III compared with
      others reporting low depressive symptoms. CONCLUSIONS: Undeniably, childhood
      socioeconomic circumstances are important determinants of disease risks and
      improved health functioning and in particular birth outcomes in adulthood. Since
      poorer households have fewer resources to cope with stressful events that
      generate mood and other depressive symptoms over the life course, findings of
      research suggest treating depressive symptoms prior to pregnancy will yield
      significant dividends for mothers and society. Furthermore, without careful
      control of household contexts, the association between depressive symptoms and
      birth outcomes is likely to be confounded.

PMID- 29331824
TI  - Effects of subject-case marking on agreement processing: ERP evidence from
      Basque.
AB  - Previous cross-linguistic research has found that comprehenders are immediately
      sensitive to various kinds of agreement violations across languages. We focused
      on Basque, a verb-final ergative language with both subject-verb (SV) and object
      verb (OV) agreement. We compared the effects of SV agreement violations on
      comprehenders' event-related brain potentials (ERPs) in transitive sentences
      (where OV agreement is present, and the subject is ergative) and intransitive
      sentences (where OV agreement is absent, and the subject is absolutive). We
      observed a P600 effect in both cases, but only violations with intransitive
      subjects elicited an early posterior negativity. Such a qualitative difference
      suggests that distinct neurocognitive mechanisms are involved in processing
      agreement with transitive subjects (which are marked with ergative case) versus
      intransitive subjects (which bear absolutive case). Building on theoretical
      proposals that in languages such as Basque, true agreement occurs with absolutive
      subjects but not with ergative subjects, we submit that the early posterior
      negativity may be an electrophysiological signature for true agreement.

PMID- 29331825
TI  - A novel strategy for the efficient removal of toxic cyanate by the combinatorial
      use of recombinant enzymes immobilized on aminosilane modified magnetic
      nanoparticles.
AB  - Cyanase detoxifies cyanate by transforming it to ammonia and carbon dioxide in a
      bicarbonate-dependent reaction, however, dependence on bicarbonate limits its
      utilization in large-scale applications. A novel strategy was therefore developed
      for overcoming this bottleneck by the combined application of cyanase (rTl-Cyn)
      and carbonic anhydrase (rTl-CA). The synergistic effect of rTl-Cyn and rTl-CA
      could reduce the dependence of bicarbonate by 80%, compared to using rTl-Cyn
      alone. Complete degradation of cyanate (4 mM) was achieved with buffered
      conditions and 85 +/- 5% degradation with industrial wastewater sample, when 20 U
      of rTl-Cyn was applied. Furthermore, a similar percentage of degradation was
      achieved using 80% less bicarbonate, when rTl-Cyn and rTl-CA were used together
      under identical conditions. In addition, rTl-Cyn and rTl-CA were immobilized onto
      the magnetic nanoparticles and their catalytic activity, stability and
      reusability were also evaluated. This is the first report on the synergistic
      biocatalysis by rTl-Cyn and rTl-CA, for cyanate detoxification.

PMID- 29331826
TI  - Pathway and mechanism of nitrogen transformation during composting: Functional
      enzymes and genes under different concentrations of PVP-AgNPs.
AB  - Polyvinylpyrrolidone coated silver nanoparticles (PVP-AgNPs) were applied at
      different concentrations to reduce total nitrogen (TN) losses and the mechanisms
      of nitrogen bio-transformation were investigated in terms of the nitrogen
      functional enzymes and genes. Results showed that mineral N in pile 3 which was
      treated with AgNPs at a concentration of 10 mg/kg compost was the highest (6.58
      g/kg dry weight (DW) compost) and the TN loss (47.07%) was the lowest at the end
      of composting. Correlation analysis indicated that TN loss was significantly
      correlated with amoA abundance. High throughput sequencing showed that the
      dominant family of ammonia-oxidizing bacteria (AOB) was Nitrosomonadaceae, and
      the number of Operational Taxonomic Units (OTUs) reduced after the beginning of
      composting when compared with day 1. In summary, treatment with AgNPs at a
      concentration of 10 mg/kg compost was considerable to reduce TN losses and
      reserve more mineral N during composting.

PMID- 29331827
TI  - Pilot-scale outdoor photobioreactor culture of the marine dinoflagellate
      Karlodinium veneficum: Production of a karlotoxins-rich extract.
AB  - A pilot-scale bioprocess was developed for the production of karlotoxin-enriched
      extracts of the marine algal dinoflagellate Karlodinium veneficum. A bubble
      column and a flat-panel photobioreactors (80-281 L) were used for comparative
      assessment of growth. Flow hydrodynamics and energy dissipation rates (EDR) in
      the bioreactors were characterized through robust computational fluid dynamic
      simulations. All cultures were conducted monoseptically outdoors. Bubble column
      (maximum cell productivity in semicontinuous operation of 58 * 103 cell mL-1 day
      1) proved to be a better culture system for this alga. In both reactors, the
      local EDR near the headspace, and in the sparger zone, were more than one order
      of magnitude higher than the average value in the whole reactor (=4 * 10-3 W kg
      1). Extraction of the culture and further purification resulted in the desired
      KTXs extracts. Apparently, the alga produced three congeners KTXs: KmTx-10 and
      its sulfated derivative (sulfo-KmTx-10) and KmTx-12. All congeners possessed
      hemolytic activity.

PMID- 29331828
TI  - A recovery time after warming restores mitochondrial function and improves
      developmental competence of vitrified ovine oocytes.
AB  - The aim of the present study was to assess the ability of vitrified/warmed oocyte
      to recover from vitrification-induced damages after warming. In vitro matured,
      vitrified/warmed ovine oocytes were assessed for developmental competence,
      mitochondrial activity and distribution, ATP, ROS and catalase levels during 6 h
      of in vitro culture using fresh oocytes as control. ATP content in vitrified
      oocytes was lower than control during 4 h of post warming culture (p < .01).
      Vitrified oocytes were able to fill this gap only after 6 h of post-warming
      incubation. Moreover, mitochondrial activity was significantly lower (p < 0.01)
      in vitrified oocytes compared to controls, and this difference was maintained up
      to 2 h of incubation. Then the activity increased and at 4 h it was higher
      compared to controls (p < 0.01). These oocytes showed an increasing rate of
      clustered distribution of mitochondria which was lower than controls during the
      first 4 h of post warming culture (p < 0.01). ROS level was significantly higher
      at 0 h in vitrified compared to control oocytes and this difference was
      maintained also at 2 h and 6 h of incubation (p < 0.01). Catalase level was
      higher in vitrified oocytes than controls (p < 0.01) during the entire culture
      period. Cleavage and blastocyst rates were lower in vitrified oocytes compared to
      control ones during the two first time point of incubation period (p < .01),
      indeed they increased significantly from 0 to 4 h of incubation post warming (p <
      0.01). The study demonstrated that vitrified/warmed oocytes need an extra time to
      restore damage due to cryopreservation procedures and to increase their
      developmental potential. Thus, time of damage recovery after vitrification could
      be used to standardize the vitrification protocols and to improve the
      developmental competence of vitrified/warmed oocytes.

PMID- 29331829
TI  - Additional small dose of prostaglandin F2alpha at timed artificial insemination
      failed to improve pregnancy risk of lactating dairy cows.
AB  - Two experiments were performed to test the hypothesis that administering
      PGF2alpha concurrent with timed artificial insemination (AI) in lactating dairy
      cows would enhance pregnancy per AI (P/AI). In experiment 1, lactating Holstein
      cows (n = 289) in one herd were enrolled after a non-pregnancy diagnosis (30-36 d
      after AI) to synchronize subsequent ovulation before AI. Cows were assigned
      randomly to receive (im) 10 mg of PGF2alpha concurrent with timed AI (Day 0;
      treatment) or no injection (control). Blood samples were collected on Days -3, 0,
      and 13 to determine serum concentrations of progesterone. Ovaries were scanned
      via transrectal ultrasonography to determine follicle diameters (Day -3),
      subsequent ovulation risk (Day 13), and total volume of luteal tissue (Day 13).
      Diagnosis of pregnancy occurred on Days 32 and 80 after AI. Ovulation risk post
      AI exceeded 90% and did not differ between treatments. In addition, PGF2alpha
      treatment only numerically increased progesterone (5.7 +/- 0.3 vs. 6.2 +/- 0.3
      ng/mL) or luteal tissue volume (8.9 +/- 0.4 vs. 9.8 +/- 0.5 ng/mL) on Day 13 by
      8.8% (P = .206) or 10.1% (P = .134) in control and treated cows, respectively.
      Pregnancy per AI at Days 32 (P = .50) and 80 (P = .33) did not differ between
      treatments. Cows with progesterone >0.5 ng/mL at timed AI had reduced (P < .001)
      ovulation risk but risk was unaffected by treatment. In experiment 2, lactating
      dairy cows (n = 1828) in two commercial dairy herds were enrolled at time of
      insemination (Day 0), and assigned randomly to treatment or control as described
      in experiment 1. Initial (Days 32-35) and confirmed (Days 63-68) pregnancy
      diagnosis revealed no differences in P/AI or pregnancy loss. Pregnancy diagnosis
      on Days 32-35 produced percentage increases in P/AI for primiparous compared with
      multiparous cows (20.8%; P = .002), for first-service compared with repeat
      service cows (26%; P = .001), and cows in one herd compared with the second herd
      (36%; P < .001). Pregnancy loss was greater (P = .001) for cows inseminated at
      first (10.0%) vs. later services (5.3%) but was unaffected by treatment. Cows
      treated with PGF2alpha in one herd produced more twins than control cows (11.7
      vs. 3.2%), whereas no treatment difference was detected in the second herd (5.6
      vs. 5.6%), respectively. We conclude that im treatment of lactating dairy cows
      with 10 mg of PGF2alpha concurrent with timed AI did not improve P/AI or embryo
      survival, but increased twinning in one herd.

PMID- 29331830
TI  - Fetal development of the Poeppig's woolly monkey (Lagothrix poeppigii).
AB  - The intrauterine development is an evolutionary strategy that prepares the
      neonate for extra-uterine life, thus providing important information on the life
      history of species. In this study, we described the external and internal
      morphology of 25 fetuses of Poeppig's woolly monkeys (Lagothrix poeppigii) by
      taking advantage of a 10-year participatory collection of biological samples
      originated from animals hunted for subsistence purposes in the Peruvian Amazon.
      Logistic regressions estimated the probability of occurrence of each external
      morphological characteristic in relation to the crown-rump length (CRL). The
      presence of nails, closed eyelids, differentiated genitalia and formed limbs with
      separation of the digits were observed in all analyzed fetuses (>=4.2 cm CRL).
      The other characteristics appeared in the following order: skin with epidermal
      pigmentation, oral and nasal mucosal pigmentation, tactile pelage and covering
      pelage. Although advanced fetuses (>15.8 cm CRL) showed most fetal external
      characteristics, they were not fully developed and no specimen showed tooth
      eruption or opened eyelids. The growth formula used to determine fetal age was ?W
      = 0.042 (t - 45), with a high linear relationship between CRL and gestational
      age. All associations between the external biometry, absolute volume of internal
      organs and the CRL had a high coefficient of determination. Advanced fetuses and
      adults showed similar relative volume of thoracic and abdominal organs, except
      for thymus and the liver with a higher and lower relative volume, respectively.
      The relative volume of the tubular gastrointestinal tract and the thymus had a
      constant increase along fetal development, and the liver showed a significant
      decrease. This study describes important morphological events for understanding
      the gestational development in the Lagothrix genus. In addition, these results
      may be useful to improve imaging techniques, contributing to the in situ and ex
      situ reproductive management of this highly hunted species in the Amazon.

PMID- 29331831
TI  - Effect of bone morphogenetic proteins 2 and 4 on survival and development of
      bovine secondary follicles cultured in vitro.
AB  - This study evaluated the effect of bone morphogenetic proteins 2 (BMP2) and 4
      (BMP2) on follicle development and mRNA expression for GDF9, Cyclin B1, BMPR1A,
      BMPR1B, BMPRII, FSHR and SMAD1 in bovine secondary follicles cultured in vitro.
      Isolated secondary follicles were cultured for 18 days in TCM199+ medium alone or
      supplemented with BMP2 (10 ng/mL), BMP4 (100 ng/mL) or combination of both BMP2
      and 4. Real-time PCR was used to analyze mRNA levels in fresh and cultured
      follicles. After 18 days of culture, follicles cultured with BMP2 alone or with
      BMP4 alone had larger diameters when compared to control (P < .05). In addition,
      all treatments promoted antrum formation and maintained a high viability rate
      through the growing period. The presence of BMP2, BMP4 or both together did not
      influence mRNA expression for the tested genes. However, the in vitro culture
      induces down-regulation for mRNA expression of BMPR1A. In conclusion, the
      addition of BMP2 or BMP4 alone in cultured medium promotes follicular growth and
      antrum formation in bovine follicles after 18 days of in vitro culture.

PMID- 29331832
TI  - Investigations on a cryopreservation protocol for long-term storage of psittacine
      spermatozoa using cockatiel semen as an example.
AB  - The aim of the present study was the establishment of an effective protocol for
      cryopreservation of psittacine semen. Therefore, pooled semen samples of 30
      cockatiels (Nymphicus hollandicus) were diluted with modified Lake diluent (1:4),
      partitioned into four equal parts. Three portions were mixed with three
      cryoprotectants (dimethylacetamide, dimethyl sulfoxide, glycerol) in 4%, 8% and
      12% final concentration, respectively, whereas the 4rth part served as control.
      Altogether, 96 incremental diluted semen samples were obtained for investigation.
      Each cryoprotective agent (CPA) in each final concentration was evaluated
      regarding sperm motility immediately after dilution and another four times every
      30 min. Sperm viability was evaluated 0 and 120 min after dilution using the
      fluorescence stain SYBR(r) Green/propidium iodide. Sperm morphology was evaluated
      0 and 120 min after dilution using eosin B stains. Glycerol demonstrated a lethal
      effect on cockatiel spermatozoa in all concentrations, whereas dimethylacetamide
      (DMA) in 8% final concentration proved to have the least adverse effect on semen
      parameters. Comparison of quick and slow freezing methods using DMA 8% revealed
      significantly higher rates of viable and motile spermatozoa after computer
      controlled rate freezing. Two insemination experiments resulted in an egg
      fertility rate of 92.59% and 67.65% after artificial insemination with freshly
      collected semen samples, compared to 30.77% and 18.00% egg fertility rates using
      frozen/thawed semen. Altogether, 12 chicks hatched out of eggs inseminated with
      cryopreserved semen. To our knowledge, this is the first time for cockatiels to
      be successfully reproduced after artificial insemination using cryopreserved
      semen.

PMID- 29331833
TI  - Potential factors that impact the radon level and the prediction of ambient dose
      equivalent rates of indoor microenvironments.
AB  - This study aimed to measure the equilibrium equivalent radon (EECRn)
      concentration in an old building (Building-1) and a new building (Building-2)
      with mechanical ventilation and a natural ventilation system, respectively. Both
      buildings were located at the campus of University Kebangsaan Malaysia. The
      concentration of indoor radon was measured at 25 sampling stations using a radon
      detector model DOSEman PRO. The sampling was conducted for 8 h to represent daily
      working hours. A correlation of the radon concentration was made with the annual
      inhalation dose of the occupants at the indoor stations. The equilibrium factor
      and the annual effective dose on the lung cancer risks of each occupant were
      calculated at each sampling station. The average equilibrium equivalent radon
      measured in Building-1 and Building-2 was 2.33 +/- 0.99 and 3.17 +/- 1.74 Bqm-3,
      respectively. The equilibrium factor for Building 1 ranged from 0.1053 to 0.2273,
      and it ranged from 0.1031 to 0.16 for Building 2. The average annual inhalation
      doses recorded at Building-1 and Building-2 were 0.014 +/- 0.005 mSv y-1 and
      0.020 +/- 0.013 mSv y-1, respectively. The annual effective dose for Building-1
      was 0.034 +/- 0.012 mSv y-1, and it was 0.048 +/- 0.031 mSv y-1 for Building-2.
      The values of equilibrium equivalent radon concentration for both buildings were
      below the standard recommended by the International Commission on Radiological
      Protection (ICRP). However, people may have different radon tolerance levels.
      Therefore, the inhalation of the radon concentration can pose a deleterious
      health effect for people in an indoor environment.

PMID- 29331834
TI  - Land-Water-Food Nexus and indications of crop adjustment for water shortage
      solution.
AB  - While agriculture places the greatest demand on water resources, increasing
      agricultural production is worsening a global water shortage. Reducing the
      cultivation of water-consuming crops may be the most effective way to reduce
      agricultural water use. However, when also taking food demand into consideration,
      sustaining the balance between regional water and food securities is a growing
      challenge. This paper addresses this task for regions where water is
      unsustainable for food production (Beijing-Tianjin-Hebei Region for example) by:
      (i) assessing the different effects of wheat and maize on water use; (ii)
      analyzing virtual water and virtual land flows associated with food imports and
      exports between Beijing-Tianjin-Hebei and elsewhere in China; (iii) identifying
      sub-regions where grain is produced using scarce water resources but exported to
      other regions; and (iv) analyzing the potentiality for mitigating water shortage
      via Land-Water-Food Nexus. In the Beijing-Tianjin-Hebei Region, the study reveals
      that 29.76 bn m3 of virtual water (10.81 bn m3 of blue virtual water) are used by
      wheat and maize production and 8.77 bn m3 of virtual water used in nearly 2
      million ha of cropland to overproduce 12 million ton of maize for external food
      consumption. As an importing-based sub-region with high population density,
      Beijing & Tianjin imported mostly grain (wheat and maize) from Shandong Province.
      Then, Hebei Province, as an exporting-based sub-region with severe water
      shortage, overproduced too much grain for other regions, which aggravated the
      water crisis. To achieve an integrated and sustainable development of the Beijing
      Tianjin-Hebei Region, Hebei Province should stop undertaking the breadbasket role
      for Beijing & Tianjin and pay more attention to groundwater depletion. The
      analysis of the Land-Water-Food Nexus indicates how shifts in cultivated crops
      can potentially solve the overuse of water resources without adverse effects on
      food supply. It also provides meaningful information to support policy decisions
      about regional cropping strategies.

PMID- 29331835
TI  - Integrating priority areas and ecological corridors into national network for
      conservation planning in China.
AB  - Considering that urban expansion and increase of human activities represent
      important threats to biodiversity and ecological processes in short and long
      term, developing protected area (PA) network with high connectivity is considered
      as a valuable conservation strategy. However, conservation planning associated
      with the large-scale network in China involves important information loopholes
      about the land cover and landscape connectivity. In this paper, we made an
      integrative analysis for the identification of conservation priority areas and
      least-cost ecological corridors (ECs) in order to promote a more representative,
      connected and efficient ecological PA network for this country. First, we used
      Zonation, a spatial prioritization software, to achieve a hierarchical mask and
      selected the top priority conservation areas. Second, we identified optimal
      linkages between two patches as corridors based on least-cost path algorithm.
      Finally, we proposed a new framework of China's PA network composed of
      conservation priority and ECs in consideration of high connectivity between
      areas. We observed that priority areas identified here cover 12.9% of the region,
      distributed mainly in mountainous and plateau areas, and only reflect a spatial
      mismatch of 19% with the current China's nature reserves locations. From the
      perspective of conservation, our result provide the need to consider new PA
      categories, specially located in the south (e.g., the middle-lower Yangtze River
      area, Nanling and Min-Zhe-Gan Mountains) and north regions (e.g., Changbai
      Mountains), in order to construct an optimal and connected national network in
      China. This information allows us better opportunities to identify the relative
      high-quality patches and draft the best conservation plan for the China's
      biodiversity in the long-term run.

PMID- 29331836
TI  - Effects of ZnO nanoparticles in the Caspian roach (Rutilus rutilus caspicus).
AB  - Most studies investigating the toxicity of zinc oxide nanoparticles (ZnO NPs)
      focused on the effect of size, whereas exposure concentration and duration
      remained poorly understood. In this study, the effect of acute and sub-acute
      exposures of ZnO NPs on Zn compartmentalization and biomarkers' expression were
      investigated in Rutilus rutilus caspicus (Caspian roach) considering various
      exposure scenarios: i) the assessment of the concentration-response curves and
      median lethal concentration (LC50); ii) the assessment of the effects of
      organisms exposed at LC50 value and one tenth of LC50 value of ZnO NPs
      suspensions for 4 d and 28 d, respectively; iii) the assessment of 14 d
      depuration period. The same concentrations of ZnSO4 were investigated. The
      highest Zn accumulation was detected in gill after sub-acute exposure (4.8 mg/L;
      28 d) followed by liver, kidney and muscle. In gill, liver and muscle, Zn from Zn
      NPs accumulated higher concentrations. Depuration (14 d) decreased Zn content in
      each organ, but no complete removal occurred except for muscle. Biomarkers'
      activity was significantly over expressed after treatments, but depuration
      brought back their values to background levels and most effects were related to
      acute concentrations (48 mg/L; 4 d) and in presence of ZnSO4. Histopathological
      analyses showed that the exposure to ZnO NPs increased lesions in gill, liver and
      kidney, with a direct proportionality between alterations and Zn accumulated in
      the target organs. After depuration, lesions regressed for both ZnO NPs and
      ZnSO4, but not in a complete way. These data could contribute to increase the
      knowledge about ZnO NPs risk assessment in aquatic vertebrates, suggesting that
      the size of ZnO NPs can influence biomarker and histopathological effects.

PMID- 29331837
TI  - Spontaneous focusing on numerosity in preschool as a predictor of mathematical
      skills and knowledge in the fifth grade.
AB  - Previous studies in a variety of countries have shown that there are substantial
      individual differences in children's spontaneous focusing on numerosity (SFON),
      and these differences are positively related to the development of early
      numerical skills in preschool and primary school. A total of 74 5-year-olds
      participated in a 7-year follow-up study, in which we explored whether SFON
      measured with very small numerosities at 5 years of age predicts mathematical
      skills and knowledge, math motivation, and reading in fifth grade at 11 years of
      age. Results show that preschool SFON is a unique predictor of arithmetic fluency
      and number line estimation but not of rational number knowledge, mathematical
      achievement, math motivation, or reading. These results hold even after taking
      into account age, IQ, working memory, digit naming, and cardinality skills. The
      results of the current study further the understanding of how preschool SFON
      tendency plays a role in the development of different formal mathematical skills
      over an extended period of time.

PMID- 29331838
TI  - Association of CAST2, HSP90AA1, DNAJA1 and HSPB1 genes with meat tenderness in
      Nellore cattle.
AB  - The objective of this study was to evaluate the association of expression of
      CAPN1, CAPN2, CAST, HSP90AA1, DNAJA1 and HSPB1 genes with meat tenderness in
      Nellore cattle. Three experimental groups were selected by shear force (SF):
      moderately tender (SF=34.3+/-5.8N), moderately tough (SF=56.8+/-7.8N), and very
      tough meat (SF=80.4+/-15N). Gene expression was evaluated by real-time PCR.
      Expression of the CAPN1, CAPN2, CAST and CAST1 genes did not differ between
      groups. Expression of the CAST2 was up-regulated (P<0.05) in the moderately tough
      and very tough meat groups. Down-regulation of the HSP90AA1, DNAJA1 and HSPB1
      genes (P<0.05) was observed in the moderately tender meat group. The present
      results suggest that meat tenderness in Nellore cattle does not directly depend
      on the expression of the CAPN1 and CAPN2 genes, but is associated with the
      expression of other genes such as CAST2, HSP90AA1, DNAJA1 and HSPB1.

PMID- 29331839
TI  - Functional characterization of a novel hERG variant in a family with recurrent
      sudden infant death syndrome: Retracting a genetic diagnosis.
AB  - Long QT syndrome (LQTS) is the most common cardiac ion channelopathy and has been
      found to be responsible for approximately 10% of sudden infant death syndrome
      (SIDS) cases. Despite increasing use of broad panels and now whole exome
      sequencing (WES) in the investigation of SIDS, the probability of identifying a
      pathogenic mutation in a SIDS victim is low. We report a family-based study who
      are afflicted by recurrent SIDS in which several members harbor a variant,
      p.Pro963Thr, in the C-terminal region of the human-ether-a-go-go (hERG) gene,
      published to be responsible for cases of LQTS type 2. Functional characterization
      was undertaken due to the variable phenotype in carriers, the discrepancy with
      published cases, and the importance of identifying a cause for recurrent deaths
      in a single family. Studies of the mutated ion channel in in vitro heterologous
      expression systems revealed that the mutation has no detectable impact on
      membrane surface expression, biophysical gating properties such as activation,
      deactivation and inactivation, or the amplitude of the protective current
      conducted by hERG channels during early repolarization. These observations
      suggest that the p.Pro963Thr mutation is not a monogenic disease-causing LQTS
      mutation despite evidence of co-segregation in two siblings affected by SIDS. Our
      findings demonstrate some of the potential pitfalls in post-mortem molecular
      testing and the importance of functional testing of gene variants in determining
      disease-causation, especially where the impacts of cascade screening can affect
      multiple generations.

PMID- 29331840
TI  - Post mortem vitreous magnesium in adult population.
AB  - BACKGROUND: The study of post mortem vitreous magnesium (Mg) is less common than
      sodium (Na), chloride (Cl) and potassium (K) in the forensic literature. There is
      no accepted normal range for post mortem vitreous Mg and the relationship between
      post mortem vitreous Mg levels and post mortem interval (PMI), other electrolyte
      levels, disease conditions, age and sex have not been fully established. AIM: To
      investigate the relationship of post mortem vitreous Mg with age, sex, PMI,
      vitreous electrolyte levels and diabetic status. METHODS: A retrospective study
      of 20 consecutive cases of diabetics and 20 non-diabetic adult deaths was
      performed. Spearman correlation and the permutation test were used to explore the
      relationship between post mortem vitreous Mg and continuous and categorical
      variables respectively. RESULTS: The mean post mortem vitreous Mg was 1.03mmol/L
      (95%CI: 0.98-1.08mmol/L). The absolute Spearman correlation coefficients (rho)
      between post mortem vitreous Mg with PMI, age, and other vitreous electrolytes
      (Na, Cl, and K) ranged between 0.04-0.21 (p>0.19). Post mortem vitreous Mg was
      statistically higher in diabetics (mean difference: 0.08mmol/L; area-under-the
      curve=0.65 on receiver-operator-characteristic curve). No statistical difference
      was demonstrated between sexes (p=0.92). CONCLUSIONS: In our adult population,
      post mortem vitreous Mg did not correlate with age, PMI, other vitreous
      electrolytes (sodium, chloride and potassium) or sex. It was higher in diabetics,
      however had limited utility as a surrogate marker. Overall, post mortem Mg is
      steady in the early post mortem period with a mean of 1.03mmol/L.

PMID- 29331841
TI  - Culture beats gender? The importance of controlling for identity- and parenting
      related risk factors in adolescent psychopathology.
AB  - This study analyzed the unique effects of gender and culture on psychopathology
      in adolescents from seven countries after controlling for factors which might
      have contributed to variations in psychopathology. In a sample 2259 adolescents
      (M = 15 years; 54% female) from France, Germany, Turkey, Greece, Peru, Pakistan,
      and Poland identity stress, coping with identity stress, maternal parenting
      (support, psychological control, anxious rearing) and psychopathology
      (internalizing, externalizing and total symptomatology) were assessed. Due to
      variations in stress perception, coping style and maternal behavior, these
      covariates were partialed out before the psychopathology scores were subjected to
      analyses of variance with gender and country as factors. These analyses leveled
      out the main effect of country and revealed country-specific gender effects. In
      four countries, males reported higher internalizing and total symptomatology than
      females. Partialing out the covariates resulted in a clearer picture of culture
      specific and gender-dependent effects on psychopathology, which is helpful in
      designing interventions.

PMID- 29331842
TI  - Predicting 1-year disability and mortality of injured older adults.
AB  - PURPOSE: The growing incidence of elderly patients injured from falls, combined
      with a growing understanding of the contribution of cognition and frailty to
      mortality, prompted this work. Our objective was to develop a clinical risk
      prediction model for prognosticating disability and mortality among injured older
      adults 1 year after hospitalization. METHODS: Secondary analysis of prospective
      longitudinal data from an urban Level 1 trauma center. A proportional odds
      regression model was used to model mortality and functional status as ordinal
      outcomes. Death was treated as the lowest functional status, and 3 ordered groups
      of the Barthel Index were treated as higher functional status. 188 patients aged
      65 and older who were admitted through the emergency department from 2013 to 2014
      with a primary injury diagnosis comprised the prospective cohort. Follow-up
      assessments were performed at 30-days, 90-days, 6-months, and 1-year. Predictors
      in the model included: baseline physical function, baseline cognition, two
      physical frailty measures, age, injury severity, a comorbidity index, gender,
      living location, mechanism of injury, and hospital admitting service. RESULTS:
      The full model yielded an R2 of 0.45, and Life Space Assessment, Vulnerable
      Elders Survey, and Injury Severity were the most influential predictors.
      Approximated models (to encourage clinical use) yielded an R2 of 0.86.
      Calibration assessment (i.e., accuracy) demonstrated a mean squared error <0.003
      at all 3 intercepts. CONCLUSIONS: A moderate statistical signal was discovered
      that contributed to a highly accurate clinical prediction model. Approximated
      models and nomograms could be used by clinicians, patients, and families in
      shared decision making during hospitalization.

PMID- 29331843
TI  - Performance of genotypic algorithms for predicting tropism for HIV-1 CRF01_AE
      recombinant.
AB  - OBJECTIVES: There is no consensus about the performances of genotypic rules for
      predicting HIV-1 non-B subtype tropism. Three genotypic methods were compared for
      CRF01_AE HIV-1 tropism determination. METHODS: The V3 env region of 207 HIV-1
      CRF01_AE and 178 B subtypes from 17 centers in France and 1 center in Switzerland
      was sequenced. Tropism was determined by Geno2Pheno algorithm with false positive
      rate (FPR) 5% or 10%, the 11/25 rule or the combined criteria of the 11/25, net
      charge rule and NXT/S mutations. RESULTS: Overall, 72.5%, 59.4%, 86.0%, 90.8% of
      the 207 HIV-1 CRF01_AE were R5-tropic viruses determined by Geno2pheno FPR5%,
      Geno2pheno FPR10%, the combined criteria and the 11/25 rule, respectively. A
      concordance of 82.6% was observed between Geno2pheno FPR5% and the combined
      criteria for CRF01_AE. The results were nearly similar for the comparison between
      Geno2pheno FPR5% and the 11/25 rule. More mismatches were observed when
      Geno2pheno was used with the FPR10%. Neither HIV viral load, nor current or nadir
      CD4 was associated with the discordance rate between the different algorithms.
      CONCLUSION: Geno2pheno predicted more X4-tropic viruses for this set of CRF01_AE
      sequences than the combined criteria or the 11/25 rule alone. For a conservative
      approach, Geno2pheno FPR5% seems to be a good compromise to predict CRF01_AE
      tropism.

PMID- 29331844
TI  - Assessing the risk of CMV reactivation and reconstitution of antiviral immune
      response post bone marrow transplantation by the QuantiFERON-CMV-assay and real
      time PCR.
AB  - BACKGROUND: CMV reactivation is a major cause of severe complications in
      allogeneic hematopoietic stem cell transplant (HSCT) recipients. The risk of CMV
      reactivation depends on the serostatus (+/-) of the donor (D) and recipient (R).
      The reconstitution of CMV-specific T-cell responses after transplantation is
      crucial for the control of CMV reactivation. OBJECTIVES: The study aimed to
      determine the cellular immune status correlating with protection from high-level
      CMV viremia (>5000 copies/ml) and disease. STUDY DESIGN: We monitored CMV
      specific cellular immune responses in 9 high-risk (D-/R+), 14 intermediate risk
      (D+/R+) and 3 low risk individuals (D+/R-), and 8 CMV negative controls (D-/R-).
      Interferon- gamma (IFN-gamma) levels as a marker for the CD8+ T-cell response
      were determined by the QuantiFERON-CMV-assay and compared to viral loads
      determined by PCR. RESULTS: Early CMV reactivation was detected in all high-risk
      and 13/14 intermediate risk individuals. High-level viremia was detected in 5/7
      high and 7/14 intermediate risk patients. Reconstitution of the CMV-specific
      cellular immune response started from 3 months after transplantation and resulted
      in protection against CMV reactivation. Re-establishing of CMV-specific T-cell
      immune responses with IFN- gamma levels >8.9 IU/ml is crucial for protection from
      high-level CMV viremia. CONCLUSIONS: Monitoring of HSCT-recipients with the
      QuantiFERON-CMV-assay might be of great benefit to optimize antiviral treatment.

PMID- 29331845
TI  - Effect of levetiracetam on extracellular amino acid levels in the dorsal
      hippocampus of rats with temporal lobe epilepsy.
AB  - Levetiracetam (LEV) is an anticonvulsant drug with a unique mechanism of action
      that is not completely understood. However, its activity profile may involve
      effects on excitatory and/or inhibitory neurotransmission since the primary
      target of LEV, synaptic vesicle protein 2A, is ubiquitously expressed in all
      types of synaptic vesicles. Therefore, the objective of the present study was to
      explore the effect of LEV (300 mg/kg/day for one week, administered via osmotic
      mini-pumps) on neurotransmitter release and its probable selective effect on
      extracellular gamma-amino butyric acid (GABA), glutamate (Glu), aspartate (Asp),
      glutamine (Gln), taurine (Tau) and glycine (Gly) concentrations (using in vivo
      microdialysis under basal and high-K+ conditions) in the dorsal hippocampus (DH),
      a region that undergoes major synaptic changes during epilepsy. Epileptic rats
      developed clear signs of hyperexcitability, i.e., an elevated Glu/GABA ratio in
      the DH. The LEV concentration in blood after 7 days of treatment was within the
      therapeutic range. In contrast, LEV was not detected four days after mini-pump
      removal (washout period). Furthermore, LEV restored the Glu/GABA ratio to
      approximately the control level and significantly increased the GABA
      concentration after the initiation of high-K+ conditions. Based on these data,
      LEV treatment restored the lost balance between the excitatory and inhibitory
      systems under basal conditions. Moreover, LEV showed a selective effect by
      preferentially increasing vesicular release of GABA, a mechanism by which LEV
      could reduce epileptic seizures.

PMID- 29331846
TI  - Functional neuroimaging in Rasmussen syndrome.
AB  - PURPOSE: For a diagnosis of Rasmussen syndrome (RS), clinical course together
      with electroencephalography (EEG) and magnetic resonance imaging (MRI) findings
      are considered important, but there are few reports on functional neuroimaging.
      This study investigated cerebral blood flow (CBF)-single photon emission computed
      tomography (SPECT), central benzodiazepine receptor (BZR)-SPECT, and fluorine-18
      fluorodeoxy glucose-positron emission tomography (FDG-PET) in RS patients, and
      correlated neuroimaging results with MRI and pathological findings. METHODS:
      Twenty-three patients diagnosed with RS according to Bien's (2005) diagnostic
      criteria (including 12 patients with a histological diagnosis) were studied. CBF
      SPECT, BZR-SPECT and FDG-PET images were visually evaluated, and the findings
      correlated with MRI and histological findings. RESULTS: Hypoperfusion areas were
      observed in 16 of 22 patients by interictal CBF-SPECT. Hyperperfusion areas were
      observed in 10 of 12 patients by ictal CBF-SPECT, which correlated with ictal
      onset area by ictal EEG (IOAE). In the limited data of BZR-SPECT in nine
      patients, lowered uptake was detected in all nine patients, including two with no
      MRI abnormalities. Lowered glucose metabolism was observed in affected areas in
      all five patients by FDG-PET. Histological examination revealed findings of
      chronic encephalitis in all 12 patients examined, concomitant with focal cortical
      dysplasia in five patients. CONCLUSION: In RS patients, functional neuroimaging
      reveals clear abnormal findings, even before the appearance of MRI abnormalities.
      BZR-SPECT and FDG-PET could detect the IOAE efficiently even in the absence of
      MRI abnormalities, while interictal CBF-SPECT occasionally failed to detect IOAE
      if MRI was normal. Based on BZR-SPECT, refractory epileptic seizures in RS may
      suggest possible impairment of inhibitory neurons.

PMID- 29331847
TI  - Longitudinal hippocampal and extra-hippocampal microstructural and
      macrostructural changes following temporal lobe epilepsy surgery.
AB  - OBJECTIVES: 1) Characterize the evolution of microstructural changes in the
      contralateral, non-operated hippocampus-using longitudinal diffusion tensor
      imaging (DTI)-following surgery for temporal lobe epilepsy (TLE). 2) Characterize
      the downstream extra-hippocampal volumetric changes of the fornix and mammillary
      bodies after TLE surgery. 3) Examine the relationship between these measures and
      seizure/cognitive outcome. METHODS: Serial structural and DTI brain MRI scans
      were collected in 25 TLE patients pre- and post-surgery (anterior temporal
      lobectomy, ATL - 13; selective amygdalohippocampectomy, SelAH - 12) and in 12
      healthy controls. Contralateral hippocampal fractional anisotropy (FA), mean
      diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) were
      computed with manual hippocampal tracings as volumes of interest following co
      registration to anatomical images. Fornix and mammillary body volumetry was
      performed by manual segmentation. RESULTS: After surgery, the non-resected
      hippocampus showed significant postoperative decline in FA (p = 0.0001), with
      increase of MD (p = 0.01) and RD (p = 0.0001). In contrast to the timing of our
      previously reported volume changes where atrophy is observed in the first week,
      diffusion changes occurred late, taking 1-3 years to develop and are not
      significant at one week after surgery. Diffusion changes are accompanied by
      delayed limbic circuit volume loss in the mammillary bodies (35%; p < 0.0001) and
      fornix (24%; p < 0.0001) compared to baseline. There was no correlation between
      postoperative diffusion or structural changes and memory score nor did the degree
      of postoperative change in hippocampal DTI parameters, mammillary body volume or
      fornix volume vary significantly based on seizure outcome. SIGNIFICANCE:
      Differences observed in the timing of postoperative volume (first week) and FA/MD
      (one year) changes would suggest that early contralateral hippocampal atrophy is
      not secondary to fluid shifts (dehydration) while the late DTI changes suggest
      ongoing microstructural changes extending beyond the early postoperative period.
      Postoperative hippocampal diffusion changes are accompanied by delayed mammillary
      body and fornix volume loss which did not differ when stratified by seizure
      outcome nor was correlated with degree of hippocampal diffusion change. Finally,
      we did not identify any significant correlation between postoperative diffusion
      parameter change and memory performance.

PMID- 29331848
TI  - Repetitive transcranial magnetic stimulation for apathy in mild cognitive
      impairment: A double-blind, randomized, sham-controlled, cross-over pilot study.
AB  - Apathy is a common and disabling behavioral concomitant of many neurodegenerative
      conditions. The presence of apathy with Mild Cognitive Impairment (MCI) is linked
      with heightened rates of conversion to Alzheimer's disease. Improving apathy may
      slow the neurodegenerative process. The objective was to establish the efficacy
      of repetitive transcranial magnetic stimulation (rTMS) in improving apathy in
      older adults with MCI. An 8-week, double-blind, randomized, sham-controlled cross
      over study was conducted in nine subjects (66 +/- 9 years) with apathy and MCI.
      Subjects were randomized to rTMS or sham treatment (5 days/week) for 2 weeks
      following which they underwent a 4-week treatment-free period. Subjects then
      crossed-over to receive the other treatment for 2 weeks. The primary (apathy (AES
      C)) and secondary (cognition (3MS & MMSE), executive function (TMT-A & TMT-B),
      and clinical global impression (CGI)) outcomes were assessed at baseline, 2, 6,
      and 8 weeks. After adjusting for baseline, there was a significantly greater
      improvement in the AES-C with rTMS compared to sham treatment at 2 weeks. There
      was significantly greater improvement in 3MS, MMSE, TMT-A, and CGI-I with rTMS
      compared to the sham treatment. This study establishes that rTMS is efficacious
      in improving apathy in subjects with MCI.

PMID- 29331849
TI  - Sociodemographic, lifestyle and health determinants of suicidal behaviour in
      Malaysia.
AB  - Suicide has become a serious matter in both developed and developing countries.
      The objective of the present study is to examine the factors affecting suicidal
      behaviour among adults in Malaysia. A nationally representative data which
      consists of 10,141 respondents is used for analysis. A trivariate probit model is
      utilised to identify the probability of having suicide ideation, suicide plan and
      suicide attempt. Results of the regression analysis show that to ensure unbiased
      estimates, a trivariate probit model should be used instead of three separate
      probit models. The determining factors of suicidal behaviour are income, age,
      gender, ethnicity, education, marital status, self-rated health and being
      diagnosed with diabetes and hypercholesterolemia. The likelihood of adopting
      suicidal behaviour is lower among higher income earners and older individuals.
      Being male and married significantly reduce the propensity to engage in suicidal
      behaviour. Of all the ethnic groups, Indian/others displays the highest
      likelihood of adopting suicidal behaviour. There is a positive relationship
      between poor health condition and suicide. Policies targeted at individuals who
      are likely to adopt suicidal behaviour may be effective in lowering the
      prevalence of suicide.

PMID- 29331850
TI  - Attentional biases in patients suffering from unipolar depression: results of a
      dot probe task investigation.
AB  - Cognitive models of depression emphasize the relevance of cognitive biases for
      development, onset and maintenance of major depressive disorder (MDD).
      Attentional biases consisting of increased attention to negative, mood congruent
      stimuli and reduced attention to positive, mood-incongruent stimuli are
      postulated but have rarely been tested for early attentional processing.
      Furthermore, the role of concurrent depressive mood as a moderating factor has
      not been studied to date. Participants comprised 30 patients suffering from MDD
      and 30 healthy control subjects. All participants performed a dot-probe task with
      pictorial stimuli displaying affective facial expressions, presented either for
      100ms or for 500ms. Attentional biases towards faces displaying joy in both MDD
      patients and control subjects and towards faces displaying pain in MDD subjects
      were found at presentation times of 100ms. In the MDD sample, the bias indices at
      100ms were correlated with concurrent depressive mood. In patients with
      pronounced depressive mood, significant biases towards happy and angry faces were
      observed that exceed the biases obtained in control subjects and patients with
      less depressive mood. The results provide first evidence that MDD patients with
      pronounced depressive mood show an increased early attentional engagement towards
      emotional salient stimuli, independent from valence.

PMID- 29331851
TI  - Rhizospheric microorganisms as a solution for the recovery of soils contaminated
      by petroleum: A review.
AB  - Petroleum is currently the world's main energy source, and its demand is expected
      to increase in coming years. Its intense exploitation can lead to an increase in
      the number of environmental accidents, such as spills and leaks, and an increase
      in the generation of environmental liabilities resulting from refining. Due to
      its hydrophobic characteristics and slow process of biodegradation, petroleum can
      remain in the environment for a long time and its toxicity can cause a negative
      impact on both terrestrial and aquatic ecosystems, with the main negative effects
      related to its carcinogenic potential for both animals and humans. The objective
      of the present review is to discuss environmental contamination by oil,
      conventional treatment techniques and bioremediation an alternative tool for
      recovery petroleum-contaminated soils, focusing on the rhizodegradation process,
      plant growth-promoting rhizobacteria (PGPR), a phytoremediation strategy in which
      the microorganisms that colonize the roots of phytoremediatior plants are
      responsible for the biodegradation of petroleum. These microorganisms can be
      selected and tested individually or in the form of consortia to evaluate their
      potential for oil degradation, or even to measure the use of biosurfactants
      produced by them to constitute tools for the development of environmental
      recovery strategies and biotechnological application.

PMID- 29331852
TI  - No time to waste organic waste: Nanosizing converts remains of food processing
      into refined materials.
AB  - Modern food processing results in considerable amounts of side-products, such as
      grape seeds, walnut shells, spent coffee grounds, and harvested tomato plants.
      These materials are still rich in valuable and biologically active substances and
      therefore of interest from the perspective of waste management and "up-cycling".
      In contrast to traditional, often time consuming and low-value uses, such as
      vermicomposting and anaerobic digestion, the complete conversion into
      nanosuspensions unlocks considerable potentials of and new applications for such
      already spent organic materials without the need of extraction and without
      producing any additional waste. In this study, nanosuspensions were produced
      using a sequence of milling and homogenization methods, including High Speed
      Stirring (HSS) and High Pressure Homogenization (HPH) which reduced the size of
      the particles to 200-400 nm. The resulting nanosuspensions demonstrated
      nematicidal and antimicrobial activity and their antioxidant activities exceeded
      the ones of the bulk materials. In the future, this simple nanosizing approach
      may fulfil several important objectives, such as reducing and turning readily
      available waste into new value and eventually closing a crucial cycle of
      agricultural products returning to their fields - with a resounding ecological
      impact in the fields of medicine, agriculture, cosmetics and fermentation.
      Moreover, up-cycling via nanosizing adds an economical promise of increased value
      to residue-free waste management.

PMID- 29331853
TI  - Mobility of heavy metals in sandy soil after application of composts produced
      from maize straw, sewage sludge and biochar.
AB  - Studies on the availability of heavy metals in composted organic materials and in
      soil amended with these materials are of practical significance. They are used in
      the assessment of the purity of the soil environment and of the biological value
      of plants intended for human and animal consumption. Composting of organic
      materials has a significant effect on changes in mobile forms of heavy metals.
      Therefore, the aim of this study was to determine the effect of the addition of
      biochar and sewage sludge on (i) the contents of water soluble forms of Cu, Cd,
      Pb, and Zn in composts; and (ii) the contents of mobile forms of these elements
      in sandy soil after the addition of composts. Addition of sewage sludge and
      biochar to maize straw did not increase the heavy metal forms extracted with
      water in total content of heavy metals. The content of Cd and Cu extracted with
      water in composts produced from maize straw and sewage sludge, and produced from
      maize straw, sewage sludge and biochar was higher than the one determined in
      compost produced from maize straw. The content of Pb and Zn extracted with water
      in compost produced from maize straw, sewage sludge and biochar was lower than in
      compost produced from maize straw. The addition of sewage sludge and biochar to
      maize straw had an immobilizing effect on mobile forms of the studied elements
      compared to compost produced from maize straw and sewage sludge. The addition of
      composts to soil decreased the contents of mobile forms of Cu, Cd, and Pb
      extracted with 1 M NH4NO3 compared to the contents in the control soil. However,
      the content of Zn extracted with NH4NO3 increased in treatments with 0.5% dose of
      compost produced from maize straw and sewage sludge and 0.5% dose of compost
      produced from maize straw, sewage sludge and biochar. In none of the analyzed
      cases, the application of the composts produced did not exceed the acceptable
      content of studied elements in the soil.

PMID- 29331854
TI  - Trade-offs between forest carbon stocks and harvests in a steady state - A multi
      criteria analysis.
AB  - This paper provides a perspective for comparing trade-offs between harvested wood
      flows and forest carbon stocks with different forest management regimes. A
      constant management regime applied to a forest area with an even age-class
      distribution leads to a steady state, in which the annual harvest and carbon
      stocks remain constant over time. As both are desirable - carbon stocks for
      mitigating climate change and harvests for the economic use of wood and
      displacing fossil fuels - an ideal strategy should be chosen from a set of
      management regimes that are Pareto-optimal in the sense of multi-criteria
      decision-making. When choosing between Pareto-optimal alternatives, the trade-off
      between carbon stock and harvests is unavoidable. This trade-off can be described
      e.g. in terms of carbon payback times or carbon returns. As numerical examples,
      we present steady-state harvest levels and carbon stocks in a Finnish boreal
      forest region for different rotation periods, thinning intensities and collection
      patterns for harvest residues. In the set of simulated management practices,
      harvest residue collection presents the most favorable trade-off with payback
      times around 30-40 years; while Pareto-optimal changes in rotation or thinnings
      exhibited payback times over 100 years, or alternatively carbon returns below 1%.
      By extending the rotation period and using less-intensive thinnings compared to
      current practices, the steady-state carbon stocks could be increased by half
      while maintaining current harvest levels. Additional cases with longer rotation
      periods should be also considered, but were here excluded due to the lack of
      reliable data on older forest stands.

PMID- 29331855
TI  - Retrievable Inferior vena cava filters in pregnancy: Risk versus benefit?
AB  - OBJECTIVE: Venous thromboembolism remains one of the leading causes of maternal
      mortality in the developed world. Retrievable inferior vena cava (IVC) filters
      have a role in the prevention of lethal pulmonary emboli when anticoagulation is
      contraindicated or has failed [1]. It is unclear whether or not the physiological
      changes in pregnancy influence efficacy and complications of these devices. The
      decision to place an IVC filter in pregnancy is complex and there is limited
      information in terms of benefit and risk to the mother. The objective of this
      study was to determine the efficacy and safety of these devices in pregnancy and
      to compare these with rates reported in the general population. STUDY DESIGN: The
      aim of this study was report three recent cases of retrievable IVC filter use in
      pregnant women in our department and to perform a systematic review of the
      literature to identify published cases of filters in pregnancy. The efficacy and
      complication rates of these devices in pregnancy were estimated and compared to
      rates reported in the general population in a recent review [2]. Fisher's exact
      test was used for statistical analysis. RESULTS: In addition to our three cases,
      16 publications were identified with retrievable IVC filter use in 40 pregnant
      women resulting in a total of 43 cases. There was no pulmonary embolus in the
      pregnant group (0/43) compared to 57/6291 (0.9%) in the general population.
      Thrombosis of the filter (2.3% vs. 0.9%, p = 0.33) and perforation of the IVC
      (7.0% vs 4.4%, p = 0.44) were more common in pregnancy compared to the general
      population but the difference was not statistically significant. Failure to
      retrieve the filter is more likely to occur in pregnancy (26% vs. 11%, p = 0.006)
      but this did not correlate with the type of device (p = 0.61), duration of
      insertion (p = 0.58) or mode of delivery (p = 0.37). CONCLUSION: Data for
      retrievable IVC filters in pregnancy is limited and there may be a publication
      bias towards complicated cases. This study shows that the filter appears to
      protect against PE in pregnancy but the numbers are small. Complications such as
      filter thrombosis and IVC penetration appear to be higher in pregnancy but this
      difference is not statistically significant. It is not possible to retrieve the
      device in one out of every four pregnant women. This has implications in terms of
      long term risk of lower limb thrombosis and post thrombotic syndrome. The
      decision to use an IVC filter in pregnancy needs careful consideration by a
      multidisciplinary team. The benefit and risk assessment should be individualised
      and clearly outlined to the patient.

PMID- 29331856
TI  - Schizandrin A enhances chemosensitivity of colon carcinoma cells to 5
      fluorouracil through up-regulation of miR-195.
AB  - Nowadays 5-fluorouracil (5-FU)-based adjuvant chemotherapy is widely used for
      treating colon carcinoma. However, 5-FU resistance in the treatment of colon
      carcinoma has become more common and thereby new therapeutic strategies and new
      adjuvant drugs still need to be explored. Two 5-FU-resistant colon cancer cell
      lines, HCT116 and SW480, were used to investigate the effects of Schizandrin A
      (SchA), 5-FU, or their combination on cell viability and apoptosis. Besides, the
      role of miR-195 was studied to further clarify the specific function of SchA. CCK
      8 assay and flow cytometry analysis were conducted to determine cell viability
      and apoptosis, respectively. miR-195 expression was determined by quantitative
      real-time PCR. Cell apoptosis-related proteins and factors of PI3K/AKT and NF
      kappaB pathways were analyzed by Western blot. Cell viability assay showed that
      SchA treatment at non-toxic dosages caused a marked enhancement of 5-FU-induced
      cytotoxicity. Moreover, we explored that miR-195 was up-regulated by SchA; and
      overexpression of miR-195 reduced cell viability and sensitized 5-FU-resistant
      HCT116 and SW480 cells to 5-FU. The promoting effect of SchA on 5-FU
      susceptibility can be partly abolished by miR-195 knockdown. Thus it was
      speculated that SchA might enhance cell chemosensitivity to 5-FU by up-regulating
      miR-195. Finally, we found that PI3K/AKT and NF-kappaB pathways were inhibited by
      high expression of miR-195 reduced by SchA. Our results suggested that SchA
      sensitized 5-FU-resistant colon carcinoma cells to 5-FU by up-regulating miR-195.
      SchA combined with 5-FU could be a promising strategy for the adjuvant
      chemotherapy of colon cancer.

PMID- 29331857
TI  - Baicalin alleviates IL-1beta-induced inflammatory injury via down-regulating miR
      126 in chondrocytes.
AB  - Baicalin is a flavonoid extracted from Scutellaria baicalensis Georgi, with anti
      inflammatory and anti-apoptotic activities. The objective of this study was to
      explore the effect and mechanism of baicalin on chondrocyte inflammatory response
      in OA. Different concentrations of IL-1beta (0, 0.1, 2, 5 and 10 ng/mL) were used
      to simulate inflammatory injury in CHON-001 cells. The expression of miR-126 was
      altered by transfection with miR-126 mimic. Thereafter, cells were treated with
      baicalin, and cell viability, apoptosis, the expressions of apoptosis-related
      protein and pro-inflammatory factors were respectively detected using CCK-8
      assay, flow cytometry, qRT-PCR and western blot analysis. We found that IL-1beta
      induced a significantly inflammatory injury in CHON-001 cells. Baicalin
      alleviated IL-1beta-induced inflammatory injury, as it increased cell viability,
      decreased cell apoptosis and repressed the production of IL-6, IL-8 and TNF
      alpha. miR-126 was up-regulated by IL-1beta treatment while was down-regulated by
      baicalin. More interestingly, the protective actions of baicalin on IL-1beta
      injured CHON-001 cells were partially eliminated by miR-126 overexpression.
      Further, NF-kappaB signaling pathway was activated by IL-1beta, and deactivated
      by addition of baicalin. The deactivation of NF-kappaB signaling pathway induced
      by baicalin upon IL-1beta exposure was recovered by miR-126 overexpression. In
      conclusion, this study demonstrated that baicalin protected CHON-001 cells
      against IL-1beta-induced inflammatory injury possibly via down-regulation of miR
      126 and thereby deactivation of NF-kappaB signaling pathway.

PMID- 29331858
TI  - Down-regulation of long non-coding RNA AFAP1-AS1 inhibits tumor growth, promotes
      apoptosis and decreases metastasis in thyroid cancer.
AB  - Long non-coding RNAs (lncRNAs), a new type of transcripts, play important roles
      in various cellular biological processes, involving tumorigenesis. Previous
      studies showed that lncRNA AFAP1-AS1 was aberrantly expressed in numerous
      cancers. Nevertheless, we know quite a little about the expression pattern and
      biological function of AFAP1-AS1 in thyroid cancer. In this study, we adopted the
      quantitative real-time PCR (qRT-PCR) to detect the expression of AFAP1-AS1 in
      thyroid cancer tissues. We discovered that expression of AFAP1-AS1 was increased
      in thyroid cancer tissues. MTT assays elucidated that down-regulation of AFAP1
      AS1 could suppress growth of thyroid cancer cells. And the results of flow
      cytometry analysis indicated knockdown of AFAP1-AS1 induced apoptosis in thyroid
      cancer. Transwell assay was applied to show decreased cell migration in thyroid
      cancer as a result of down-regulation of AFAP1-AS1. Hence, our study provided
      evidence for our hypothesis that AFAP1-AS1 could be a therapeutic target for
      thyroid cancer.

PMID- 29331859
TI  - Development of a method to determine axitinib, lapatinib and afatinib in plasma
      by micellar liquid chromatography and validation by the European Medicines Agency
      guidelines.
AB  - A method based on micellar liquid chromatography to quantify the tyrosine kinase
      inhibitors axitinib, lapatinib and afatinib in plasma is reported. The sample
      pretreatment was a simple 1/5-dilution in a pure micellar solution, filtration
      and direct injection, without requiring extraction or purification steps. The
      three drugs were resolved from the matrix in 17min, using an aqueous solution of
      0.07M sodium dodecyl sulfate - 6.0% 1-pentanol, buffered at pH7 with 0.01M
      phosphate salt as mobile phase, running under isocratic mode at 1mL/min through a
      C18 column. The detection was performed by absorbance at 260nm. An accurate
      mathematical relationship was established between the retention factor of each
      drug and the surfactant/organic solvent concentration in the mobile phase,
      achieved with a limited number of experiments, in order to optimize these
      factors. A binding behavior of the analytes face to the micelles was found out.
      The method was successfully validated by the guidelines of the European Medicines
      Agency in terms of: selectivity, linearity (r2>0.9995), calibration range (0.5 to
      10mg/L), limit of detection (0.2mg/L), carry-over effect, accuracy (-8.1 to
      +6.9%), precision (<13.8%), dilution integrity, matrix effect, stability and
      robustness. The procedure was found reliable, practical, economic, accessible,
      short-time, easy-to-handle, inexpensive, environmental-friendly, safe, useful for
      the analysis of many samples per day. Finally, the method was applied to the
      analysis of incurred, using quality control samples in the same analytical run,
      with adequate results. Therefore, it can be implementable for routine analysis in
      clinical laboratories.

PMID- 29331860
TI  - C18 core-shell column with in-series absorbance and fluorescence detection for
      simultaneous monitoring of changes in stilbenoid and proanthocyanidin
      concentrations during grape cane storage.
AB  - Grape canes, the residues from the annual pruning of vines, contain high levels
      of inducible (E)-resveratrol and also oligomeric stilbenoids and
      proanthocyanidins. These two families of phenolic compounds are bioactive, but to
      quantify them in a single chromatographic run using only ultraviolet detection is
      a difficult task. To overcome this limitation, a chromatographic method was
      developed using a core shell column for separation, an ultraviolet-visible diode
      array detector (DAD) and a fluorescence (FL) detector connected in series for
      quantification, with an electrospray ionization interface (ESI) and a triple
      quadrupole mass spectrometric detector (MS/MS) added for identification of the
      analytes. The proanthocyanidins (+)-catechin, (-)-epicatechin, procyanidins B1,
      B2, and C1, an unknown dimer and trimer, two prodelphinidin dimers, and
      monogallate procyanidin dimers were detected in the tested grape cane samples.
      The stilbenoids detected were (E)-resveratrol, (E)-piceatannol, (E)-piceid, (E)
      epsilon-viniferin, vitisin B, a glycosylated monomer, three oxidized dimers, an
      unknown dimer and a tetramer, pallidol, hopeaphenol, (E)-delta-viniferin, and (E)
      omega-viniferin. However, this method required 60min for each analysis. A faster
      and more efficient method for quantitative analysis was developed based on HPLC
      DAD-FL, reducing the time required to 24min for the simultaneous quantification
      of proanthocyanidins and stilbenoids in Cabernet Sauvignon, Pinot Noir, and
      Tintorera grape canes stored at controlled temperatures and relativity humidities
      for 134days after pruning. To the best of our knowledge, this is the first time a
      prodelphinidin dimer has been quantified in grape canes. The incorporation of
      fluorescence detection in series with DAD not only allowed the quantification of
      proanthocyanidins, it also improved the detectability of some minor stilbenoids
      present in the canes, such as (E)-piceid. The (E)-resveratrol and (E)-piceatannol
      levels increased significantly during cane storage, while those of (E)-epsilon
      viniferin and ampelopsin A did not show significant increases. The relative
      humidity had a determining effect on the levels of (E)-resveratrol and (E)
      piceatannol in the canes of all varieties studied; their concentrations were
      higher at a relative humidity of 60% than at 70%. This is the first time that the
      proanthocyanidin profiles of canes stored after pruning were monitored under
      controlled conditions of temperature, time and relative humidity. The
      concentration of (-)-epicatechin decreased during storage under both relative
      humidities. Furthermore, the levels of proanthocyanidin B1 and the prodelphinidin
      dimer also decreased to a certain extent.

PMID- 29331861
TI  - Synthesis of colloidal silver nanoparticle clusters and their application in
      ascorbic acid detection by SERS.
AB  - Ascorbic acid (vitamin C) has an essential role in the human body mainly due to
      its antioxidant function. In this work, metallic silver nanoparticle (AgNP)
      colloids were used in SERS experiments to detect ascorbic acid in aqueous
      solution. The AgNPs were synthesized by a green method using potato starch as
      reducing and stabilizing agent, and water as the solvent. The optical properties
      of the yellowish as-synthesized silver colloids were characterized by UV-vis
      spectroscopy, in which besides a typical band at 410 nm related to the localized
      surface plasmon resonance of the silver nanoparticles, a shoulder band around 500
      nm, due to silver nanoparticle cluster formation, is presented when relatively
      higher concentrations of starch are used in the synthesis. These starch-capped
      silver nanoparticles show an intrinsic Raman peak at 1386 cm-1 assigned to
      deformation modes of the starch structure. The increase of the intensity of the
      SERS peak at 1386 cm-1 with an increase in the concentration of the ascorbic acid
      is related to a decrease of the gap between dimers and trimers of the silver
      nanoparticle clusters produced by the presence of ascorbic acid in the colloid.
      The limit of detection of this technique for ascorbic acid is 0.02 mM with a
      measurement concentration range of 0.02-10 mM, which is relevant for the
      application of this method for detecting ascorbic acid in biological specimen.

PMID- 29331862
TI  - Preliminary investigation of the use of Raman spectroscopy to predict meat and
      eating quality traits of beef loins.
AB  - A preliminary investigation was conducted to determine the potential for a
      handheld Raman spectroscopic device to predict sensory traits determined by an
      untrained consumer panel. Measurement of 45 beef loins (M. longissimus lumborum)
      was conducted using a 671nm handheld Raman spectroscopic device. Samples were
      then held frozen until testing by an untrained sensory panel. Sections were also
      excised to determine shear force values and other indicators of meat quality.
      Derived models suggest that the Raman spectroscopic device can predict juiciness
      and tenderness, with correlations between predicted and observed values (rho) of
      0.42 and 0.47, respectively. Spectra indicated that these predictions were
      characterised by the fatty acid concentration, the hydrophobicity of proteins and
      the orientation of collagen. However, future research is required to determine
      the repeatability and robustness of these models on a larger independent data
      set.

PMID- 29331863
TI  - Airborne volatile aromatic hydrocarbons at an urban monitoring station in Korea
      from 2013 to 2015.
AB  - The concentrations of C6-C10 volatile aromatic hydrocarbons (AHCs) in air were
      measured at an urban air quality monitoring station in Jong-Ro, Seoul, Korea,
      between 2013 and 2015. Their temporal patterns (e.g., diurnal, intraweek, daily)
      were assessed individually and collectively as groups of benzene, toluene,
      ethylbenzene, styrene, and xylene (BTESX); total aliphatic hydrocarbon (TALHC: C2
      C12); total aromatic hydrocarbon (TARHC: C6-C10); and total hydrocarbon (THC: C2
      C12). The highest mean AHC concentrations over the 3-year study (in ppb (v/v))
      were observed for toluene (6.0 +/- 4.3), followed by the xylenes (1.5 +/- 1.3),
      ethylbenzene (0.85 +/- 0.93), benzene (0.73 +/- 0.77), and styrene (0.16 +/-
      0.30) nL/L. The mean ppbC ((v/v), nL?atm?C/nL?atm) values for BTESX, TALHC,
      TARHC, and THC were 65.8, 113, 77.7, and 191 ppbC, respectively. For most AHC
      species (e.g., toluene, styrene, and BTESX), only weak seasonal trends were
      observed in contrast to temporally varying species like nitric oxide (NO) (e.g.,
      26.3 ppb (January-February) vs. 8.5 ppb (July-August) during weekdays in 2013).
      Furthermore, toluene and NO concentrations were much higher (up to a factor 3) on
      weekdays than on Sunday for most weeks. This might reflect reduced anthropogenic
      activities on Sunday.

PMID- 29331864
TI  - Taxonomic studies on Aegyria apoliva sp. nov. and Trithigmostoma cucullulus
      (Muller, 1786) Jankowski, 1967 (Ciliophora, Cyrtophoria) with phylogenetic
      analyses.
AB  - The morphology, including the ciliary pattern, of two cyrtophorid ciliates,
      namely Aegyria apoliva sp. nov. and Trithigmostoma cucullulus (Muller, 1786)
      Jankowski, 1967, were investigated. They were isolated from coastal water off
      Qingdao and from an estuarine habitat in south China, respectively. Aegyria
      apoliva sp. nov. is characterized as following: body size 100-120 * 50-70 MUm in
      vivo with dark pigment spot on anterior left part of cell; 48-69 somatic
      kineties; one preoral and four or five circumoral kineties; 9-13 transpodial
      segments; 26-40 nematodesmal rods; 6-10 contractile vacuoles. The Guangzhou
      population of Trithigmostoma cucullulus corresponds well with previously
      described populations, therefore only a brief morphological description is
      presented. Phylogenetic analysis based on small-subunit rRNA gene sequences data
      supports the establishment of the new species as well as the monophyly of both
      genera.

PMID- 29331865
TI  - Structure-based assessment of protein-protein interactions and accessibility of
      protein IX in adenoviruses with implications for antigen display.
AB  - The exterior minor protein IX of adenoviruses (AdVs) is a frequent target of
      attachment of antigens and the modified AdVs are being used as potent vaccine
      platforms. The organization of protein IX is disticntly different between human
      adenoviruses (HAdVs) and non-HAdVs. The analysis of solvent accessibility, based
      on the near atomic resolution structures, suggests that the C-terminal residues
      of IX are more accessible in non-HAdVs (e.g., bovine adenovirus) than in HAdVs.
      Although the C-terminal fusions of IX are displayed on the capsid surface, they
      could disrupt the formation of tetrameric coiled-coils (4-HLXB) in HAdVs due to
      steric hinderance, thereby potentially affecting the capsid stability.
      Importantly, the parallel-antiparallel arrangement of helices seen in the 4-HLXB
      is not condusive for IX C-terminal fusions in HAdVs. In contrast, the parallel
      trimeric C-terminal coiled-coils in non-HAdVs are unlikely to be affected by the
      attachment of antigens and more efficiently displayed on the AdV surface.

PMID- 29331868
TI  - Zinc supplementation alleviates the progression of diabetic nephropathy by
      inhibiting the overexpression of oxidative-stress-mediated molecular markers in
      streptozotocin-induced experimental rats.
AB  - Zinc deficiency during diabetes projects a role for zinc nutrition in the
      management of diabetic nephropathy. The current study explored whether zinc
      supplementation protects against diabetic nephropathy through modulation of
      kidney oxidative stress and stress-induced expression related to the inflammatory
      process in streptozotocin-induced diabetic rats. Groups of hyperglycemic rats
      were exposed to dietary interventions for 6 weeks with zinc supplementation (5
      times and 10 times the normal level). Supplemental-zinc-fed diabetic groups
      showed a significant reversal of increased kidney weight and creatinine
      clearance. There was a significant reduction in hyperlipidemic condition along
      with improved PUFA:SFA ratio in the renal tissue. Expression of the lipid
      oxidative marker and expression of inflammatory markers, cytokines, fibrosis
      factors and apoptotic regulatory proteins observed in diabetic kidney were
      beneficially modulated by zinc supplementation, the ameliorative effect being
      concomitant with elevated antiapoptosis. There was a significant reduction in
      advanced glycation, expression of the receptor of the glycated products and
      oxidative stress markers. Zinc supplementation countered the higher activity and
      expression of polyol pathway enzymes in the kidney. Overexpression of the glucose
      transporters, as an adaptation to the increased need for glucose transport in
      diabetic condition, was minimized by zinc treatment. The pathological
      abnormalities in the renal architecture of diabetic animals were corrected by
      zinc intervention. Thus, dietary zinc supplementation has a significant
      beneficial effect in the control of diabetic nephropathy. This was exerted
      through a protective influence on oxidative-stress-induced cytokines,
      inflammatory proliferation and consequent renal injury.

PMID- 29331866
TI  - Development of a novel equine influenza virus live-attenuated vaccine.
AB  - H3N8 equine influenza virus (EIV) is an important and significant respiratory
      pathogen of horses. EIV is enzootic in Europe and North America, mainly due to
      the suboptimal efficacy of current vaccines. We describe, for the first time, the
      generation of a temperature sensitive (ts) H3N8 EIV live-attenuated influenza
      vaccine (LAIV) using reverse-genetics approaches. Our EIV LAIV was attenuated
      (att) in vivo and able to induce, upon a single intranasal administration,
      protection against H3N8 EIV wild-type (WT) challenge in both a mouse model and
      the natural host, the horse. Notably, since our EIV LAIV was generated using
      reverse genetics, the vaccine can be easily updated against drifting or emerging
      strains of EIV using the safety backbone of our EIV LAIV as master donor virus
      (MDV). These results demonstrate the feasibility of implementing a novel EIV LAIV
      approach for the prevention and control of currently circulating H3N8 EIVs in
      horse populations.

PMID- 29331869
TI  - Dietary naringenin supplementation attenuates experimental autoimmune
      encephalomyelitis by modulating autoimmune inflammatory responses in mice.
AB  - Autoimmune disease is highly prevalent in humans. Since conventional therapies
      have limited efficacy and often come with significant side effects, nutrition may
      provide an alternative and complementary approach to improving autoimmune
      disorders. Naringenin, a flavonoid found in citrus fruits, has been shown to have
      anti-inflammatory and antioxidant properties. Using the experimental autoimmune
      encephalomyelitis (EAE), a rodent model of human multiple sclerosis, we
      determined the effect of dietary naringenin (0.5%) on autoimmune disease. We
      found that naringenin reduced the incidence, delayed the onset, and attenuated
      the symptoms of EAE, which were accompanied by reduced immune cell infiltration
      and demyelination in the spinal cord. Additionally, the pro-inflammatory CD4+ T
      cell subsets Th1, Th9, and Th17 cells together with their respective
      transcription factors T-bet, PU.1, and RORgammat were reduced in both the central
      nervous system (CNS) and lymph nodes of EAE mice fed naringenin while no
      difference was found in Th2 and regulatory T cell (Treg) populations in either
      CNS or lymph nodes between the two groups. We further showed that pathologic T
      cell proliferation induced by ex vivo re-stimulation with MOG35-55 and
      proinflammatory cytokines IL-6 and TNF-alpha were lower in naringenin-fed mice
      than in the control mice. Additionally, we found that naringenin treatment
      inhibited mRNA expression of CXCL10 (Th1 recruiting chemokine), vascular cell
      adhesion molecule-1 (VCAM-1), and VLA-4 (VCAM-1 ligand) in the CNS of EAE mice.
      Altogether, these results indicate that naringenin may have a potential to
      ameliorate autoimmune disease by favorably modulating autoimmune response.

PMID- 29331867
TI  - Classification and evolution of human papillomavirus genome variants: Alpha-5
      (HPV26, 51, 69, 82), Alpha-6 (HPV30, 53, 56, 66), Alpha-11 (HPV34, 73), Alpha-13
      (HPV54) and Alpha-3 (HPV61).
AB  - HPV variants from the same type can be classified into lineages and sublineages
      based on the complete genome differences and the phylogenetic topologies. We
      examined nucleotide variations of twelve HPV types within the species Alpha-5
      (HPV26, 51, 69, 82), Alpha-6 (HPV30, 53, 56, 66), Alpha-11 (HPV34, 73), Alpha-13
      (HPV54) and Alpha-3 (HPV61) by analyzing 1432 partial sequences and 181 complete
      genomes from multiple geographic populations. The inter-lineage and inter
      sublineage mean differences of HPV variants ranged between 0.9-7.3% and 0.3-0.9%,
      respectively. The heterogeneity and phylogenies of HPV isolates indicate an
      independent evolutionary history for each type. The noncoding regions were the
      most variable regions whereas the capsid proteins were relatively conserved.
      Certain variant lineages and/or sublineages were geographically-associated. These
      data provide the basis to further classify HPV variants and should foster future
      studies on the evolution of HPV genomes and the associations of HPV variants with
      cancer risk.

PMID- 29331870
TI  - Postural instability differences between idiopathic normal pressure hydrocephalus
      and Parkinson's disease.
AB  - OBJECTIVES: We investigated the differences in postural control disability
      between idiopathic normal pressure hydrocephalus (iNPH) and Parkinson's disease
      (PD). PATIENTS AND METHODS: Twenty-seven iNPH patients, 20 PD patients, and 20
      healthy controls (HCs) were examined using the Timed Up and Go test (TUG) and a
      force platform for recording the center of pressure (COP) trajectory during
      quiescent standing and voluntary multidirectional leaning (forward, backward,
      right, and left for 10 s each). RESULTS: In the leaning task, postural control in
      PD patients was impaired during forward and backward leaning, whereas postural
      control in iNPH patients was impaired in all directions. In particular, postural
      control during right and left leaning was significantly worse in iNPH patients
      than in PD patients. No significant difference was observed between iNPH and PD
      patients in TUG and postural sway during quiescent standing. CONCLUSION: Our
      results showed that the characteristics of impaired voluntary COP control in iNPH
      and PD patients might reflect pathophysiological differences in postural
      instability for each disease. In particular, postural instability during right
      and left leaning in iNPH patients may be responsible for wider steps and a higher
      risk of falling.

PMID- 29331871
TI  - Rupture during coiling of intracranial aneurysms: Predictors and clinical
      outcome.
AB  - INTRODUCTION: The intraprocedural aneurysm rupture (IPR) is one of the most
      feared adverse effect associated with the coil embolization therapy. The aim of
      the study was to identify predisposing factors for IPR, as well as to define
      patient groups with worse clinical outcome following IPR. PATIENTS AND METHODS:
      From February 2008 to March 2015, 273 consecutive patients were treated at our
      institution via endovascular coil embolization. Patient medical records were
      reviewed with emphasis on procedure description, potential risk factors and
      clinical outcomes related to IPR. The IPR occurred in 14 (5.13%) cases.
      Multivariate logistic regression models were used to determine independent
      predictors of IPR. Clinical outcome was analyzed using the Glasgow Outcome Scale
      (GOS). RESULTS: Multivariate analysis showed that aneurysm location at posterior
      communicating artery is an independent risk factor for IPR (p = 0.035; OR 3.5;
      95%CI 1.09-11.26). The frequencies of favorable disability (GOS 4-5), severe
      disability (GOS 2-3), and mortality (GOS 1) between patients with IPR and without
      IPR were significantly different in the general study population (p < 0.001, p <
      0.001 and p = 0.023, respectively) and in patients with previously unruptured
      aneurysms (p < 0.001, p = 0.006 and p = 0.003, respectively) but not in patients
      with previously ruptured aneurysms (p = 0.187, p = 0.089 and p = 1.0,
      respectively). CONCLUSION: Posterior communicating artery aneurysm location is an
      independent predictor for IPR. IPR is associated with a significant clinical
      deterioration in a subgroup of patients with previously unruptured aneurysms, but
      not in patients with ruptured aneurysms.

PMID- 29331873
TI  - Epilepsy and ovarian failure: Two cases of adolescent-onset ovarioleukodystrophy.
AB  - Vanishing white matter disease (VWM) was described by Van der Knaap in 1996. This
      association with premature ovarian failure is known as ovarioleukodystrophy. This
      is a rare entity caused by a mutation in one of the subunits of eukaryotic
      initiation factor 2B (EIF2B). The onset in adulthood or late in adolescence is
      very infrequent. A 41-years-old woman and her 37-years-old sister developed
      epilepsy in association with premature ovarian failure at the age of 13 and 18
      respectively. The oldest-one started 17 years later progressive subcortical
      cognitive decline with predominant behavioural disorders and a progressive
      spastic paraparesis in association with symmetric cystic changes in the with
      matter of both hemispheres. In both patients we found the c.1117C>T (p.Arg373Cys)
      mutation in homozygosis in the EIF2B4 gen.

PMID- 29331872
TI  - Effect of physical activity on cognitive flexibility, depression and RBD in
      healthy elderly.
AB  - OBJECTIVE: The prevalence of Alzheimer's disease and Parkinson's disease
      increases with the raising number of elderly, which will be a challenging
      situation for the healthcare systems and society in the future. There is evidence
      that there are modifiable risk-factors e.g. physical activity for these diseases.
      Here, we study the interaction between sports inactivity with prodromal markers
      for neurodegeneration. PATIENTS AND METHODS: We investigated 667 neurologically
      healthy individuals cross-sectional and a subgroup longitudinal over six years.
      Participants were stratified by their weekly sports activity. Prodromal markers
      (depression and REM sleep behaviour disorder (RBD)) as well as single and dual
      tasking parameters and cognitive parameters were compared between the groups.
      RESULTS: At baseline, sports activity was associated with lower BDI scores, lower
      occurrence of depressive syndrome and RBD, compared to sports inactivity.
      Further, active participants were faster in cognitive tasks associated with
      working memory and attention (Trail Making test part-A; TMT-B, DeltaTMT-B-A) and
      better in gait and cognition parameters (single tasks and dual tasks) but not
      with overall cognition as measured with the MMSE. The association between
      physical inactivity and depression as well as TMT was present after six years.
      CONCLUSION: We found that sports activity has a positive effect on cognitive
      flexibility, depressive symptoms and sleep which are all signs for a possible
      ongoing neurodegenerative process. Therefore, our results strengthen the
      potential role of sports activity as a positive disease modifier.

PMID- 29331874
TI  - Thyroid hormone resuscitation after brain death in potential organ donors: A
      primer for neurocritical care providers and narrative review of the literature.
AB  - Solid organ transplantation has become a mainstay in the contemporary management
      of end-stage organ failures fueled by advances in immunosuppression, intensive
      care and surgical technology. Every year, a vast number of transplantable organs
      is lost on account of hemodynamic instability in potential brain-dead organ
      donors. Because of a growing organ shortage, measures that increase total donor
      supply pools are desperately needed. Thyroid hormone has been identified as an
      adjunctive therapy in donor management due to its potential for increasing organ
      supply and is currently endorsed by transplant organizations such as United
      Network for Organ Sharing (UNOS). Much of the evidence in support of thyroid
      hormone comes from level III studies showing greater donor survival and
      procurement rates. However, all prospective randomized studies to date have
      failed to corroborate any such benefit. Here, we describe the role of thyroid
      hormone in transplantation medicine and summarize data on its putative
      contributions to circulatory stability, organ yield and long-term graft function.
      At present, level I studies do not exist and many level II studies, which do not
      endorse its use, are of poor quality. Further research, particularly large-scale
      multi-center trials are therefore warranted to shed light on this matter.

PMID- 29331875
TI  - The association between vitamin D receptor polymorphisms and multiple sclerosis
      in a Turkish population.
AB  - BACKGROUND: Multiple sclerosis (MS) is a chronic, demyelinating disease of the
      central nervous system (CNS). Genetic and environmental factors are important in
      disease development. Many studies have investigated the relationship between MS
      and VDR polymorphisms. VDR gene polymorphism has not been previously studied in
      Turkish MS patients. We aimed to investigate the relationship between MS and VDR
      genotypes Taq I, Apa I and Fok I polymorphisms in a Turkish population. METHODS:
      167 MS patients and 146 healthy control subjects were included in the present
      study. MS and the VDR TaqI (rs731236), ApaI (rs7975232), and FokI (rs2228570)
      polymorphisms were investigated. RESULTS: The study enrolled 167 patients (121
      females, 46 males) with MS and 146 healthy individuals (88 females, 58 males).
      The frequency of only the Fok I polymorphism differed significantly between the
      two groups (p = 0.002). The TaqI (rs731236) and ApaI (rs7975232) genotype
      distributions were not significantly different between MS patients and healthy
      controls (p = 0.626 and p = 0.990, respectively). Also there were no significant
      gender difference between patients and controls for Taq I and Apa I. CONCLUSION:
      In conclusion, we found a significant association between MS and the FokI
      polymorphism in our region of Turkey. However, the results may be different in
      other populations. More epidemiological and genetic studies are needed to explain
      the association between genetic factors and MS.

PMID- 29331876
TI  - APP/Go protein Gbetagamma-complex signaling mediates Abeta degeneration and
      cognitive impairment in Alzheimer's disease models.
AB  - Deposition of amyloid-beta (Abeta), the proteolytic product of the amyloid
      precursor protein (APP), might cause neurodegeneration and cognitive decline in
      Alzheimer's disease (AD). However, the direct involvement of APP in the mechanism
      of Abeta-induced degeneration in AD remains on debate. Here, we analyzed the
      interaction of APP with heterotrimeric Go protein in primary hippocampal cultures
      and found that Abeta deposition dramatically enhanced APP-Go protein interaction
      in dystrophic neurites. APP overexpression rendered neurons vulnerable to Abeta
      toxicity by a mechanism that required Go-Gbetagamma complex signaling and p38
      mitogen-activated protein kinase activation. Gallein, a selective pharmacological
      inhibitor of Gbetagamma complex, inhibited Abeta-induced dendritic and axonal
      dystrophy, abnormal tau phosphorylation, synaptic loss, and neuronal cell death
      in hippocampal neurons expressing endogenous protein levels. In the 3xTg-AD mice,
      intrahippocampal application of gallein reversed memory impairment associated
      with early Abeta pathology. Our data provide further evidence for the involvement
      of APP/Go protein in Abeta-induced degeneration and reveal that Gbetagamma
      complex is a signaling target potentially relevant for developing therapies for
      halting Abeta degeneration in AD.

PMID- 29331878
TI  - How shared reality is created in interpersonal communication.
AB  - Communication is a key arena and means for shared-reality creation. Most studies
      explicitly devoted to shared reality have focused on the opening part of a
      conversation, that is, a speaker's initial message to an audience. The aspect of
      communication examined by this research is the evaluative adaptation (tuning) of
      the messages to the audience's attitude or judgment. The speaker's shared-reality
      creation is typically assessed by the extent to which the speaker's evaluative
      representation of the topic matches the audience-tuned view expressed in the
      message. We first review research on such audience-tuning effects, with a focus
      on shared-reality goals and conditions facilitating the generalization of shared
      reality. We then review studies using other paradigms that illustrate factors of
      shared-reality creation in communication, including mere message production,
      grounding, validation responses, and communication about commonly known
      information (including stereotypes) in intragroup communication. The different
      lines of research reveal the potency, but also boundary conditions, of
      communication effects on shared reality.

PMID- 29331877
TI  - Cerebral changes and disrupted gray matter cortical networks in asymptomatic
      older adults at risk for Alzheimer's disease.
AB  - The diagnostic value of cerebrospinal fluid (CSF) biomarkers is well established
      in Alzheimer's disease, but our current knowledge about how abnormal CSF levels
      affect cerebral integrity, at local and network levels, is incomplete in
      asymptomatic older adults. Here, we have collected CSF samples and performed
      structural magnetic resonance imaging scans in cognitively normal elderly as part
      of a cross-sectional multicenter study (SIGNAL project). To identify group
      differences in cortical thickness, white matter volume, and properties of
      structural networks, participants were split into controls (N = 20), positive
      amyloid-beta (Abeta1-42+) (N = 19), and positive phosphorylated tau (N = 18). The
      Abeta1-42+ group exhibited thickening of middle temporal regions, while positive
      phosphorylated tau individuals showed thinning in the superior parietal and
      orbitofrontal cortices. Subjects with abnormal CSF biomarkers further showed
      regional white matter atrophy and more segregated cortical networks, the Abeta1
      42+ group showing heightened isolation of cingulate and temporal cortices.
      Collectively, these findings highlight the relevance of combining structural
      brain imaging and connectomics for in vivo tracking of Alzheimer's disease
      lesions in asymptomatic stages.

PMID- 29331879
TI  - Structural and quantum mechanical computations to elucidate the altered binding
      mechanism of metal and drug with pyrazinamidase from Mycobacterium tuberculosis
      due to mutagenicity.
AB  - Pyrazinamide is known to be the most effective treatment against tuberculosis
      disease and is known to have bacteriostatic action. By targeting the bacterial
      spores, this drug reduces the chances for the progression of the infection in
      organisms. In recent years, increased instances of the drug resistance of
      bacterial strains are reported. Pyrazinamidase, activator for pyrazinamide, leads
      to resistance against the drug due to mutagenicity across the world. The present
      study aimed at the quantum mechanistic analysis of mutations in pyrazinamidase to
      gain insights into the mechanism of this enzyme. Quantum mechanical calculations
      were performed to analyse the effect of mutations at the metal coordination site
      using ORCA software program. Moreover, conformational changes in PZase binding
      cavity has also been analysed due to mutations of binding pocket residues using
      CASTp server. In order to elucidate the behaviour of the mutant pyrazinamidase,
      docking of PZA in the binding pocket of PZase was performed using AutoDock Vina.
      Analysis of results revealed that iron showed weak binding with the metal
      coordination site of the mutant proteins due to alteration in electron transfer
      mechanism. The binding cavity of the mutant PZase has undergone major
      conformational changes as the volume of pocket increased due to bulky R-chains of
      mutated amino acids. These conformational changes lead to weak binding of the
      drug at binding cavity of PZase and reduce the drug activation mechanism leading
      to increased drug resistance in the bacterial strains.

PMID- 29331881
TI  - Ameliorative role of genistein against age-dependent chronic arsenic toxicity in
      murine brains via the regulation of oxidative stress and inflammatory signaling
      cascades.
AB  - Brain is highly prone to oxidative damage due to its huge lipid content and
      extensive energy requirements. Exogenous insult in brain via oxidative injury can
      lead to severe pathophysiological conditions. Age-dependent deterioration of
      normal brain functions is also noteworthy. Genistein, a polyphenolic
      isoflavonoid, obtained from the soy plant, is well known to protect against
      several diseased conditions. Here, in this study chronic brain toxicity model was
      developed using oral administration of arsenic for 90 days in adult and aged
      murines. We observed that intraperitoneal administration of genistein improved
      the arsenic induced behavioral abnormalities in the rats. It was also evident
      from the histopathological studies that the extent of tissue damage due to
      arsenic exposure was more in aged rats compared to the adults. Evaluation of
      different stress markers, intracellular ROS level and mitochondrial membrane
      potential revealed the involvement of oxidative stress and mitochondrial
      dysfunction in inducing brain damage in arsenic exposed murines. It was observed
      that genistein can significantly ameliorate the stressed condition in both the
      animal groups but the protective effect of genistein was more significant in the
      adult animals. The underlying signalling mechanism behind the cytotoxicity of
      arsenic was investigated and revealed that genistein exhibited neuroprotection
      significantly by modulating the JNK3 mediated apoptosis, ERK1/2 mediated
      autophagy and TNFalpha associated inflammatory pathways. Overall study infers
      that genistein has significant ameliorative effect of against age-dependent
      cytotoxicity of arsenic in murine brains.

PMID- 29331882
TI  - Association analysis of SLC6A4 and HTR2A genes with obsessive-compulsive
      disorder: Influence of the STin2 polymorphism.
AB  - BACKGROUND: Obsessive-Compulsive Disorder (OCD) is a complex and chronic disorder
      characterized by recurrent thoughts and/or repetitive behaviors. Given the potent
      anti-obsessional effects of the so-called serotonin reuptake inhibitors, genes
      related to serotonergic system may be well implicated in the etiopathogenesis of
      OCD. The gene encoding the serotonin transporter (SLC6A4), which shows a variable
      number of tandem repeat (VNTR) polymorphism in intron 2 (STin2), have been
      previously associated with OCD. Additionally, the serotonin 2A receptor gene
      (HTR2A) has two polymorphisms (A-1438G - rs6311, and T102C - rs6313), which have
      also been overrepresented among OCD patients. Therefore, the aim of this study is
      to evaluate the association of these three polymorphisms with OCD, through the
      examination of potential sources of heterogeneity in previous studies including
      age of onset, sex and symptom dimensions. METHODS: Polymorphisms were genotyped
      by Polymerase Chain Reaction (PCR) in a sample of 203 OCD patients and 205
      healthy controls from Brazil. RESULTS: Although we did not observe any
      statistically significant association between the HTR2A gene polymorphisms and
      OCD or its clinical features, SLC6A4 STin2 polymorphism was significantly more
      common among OCD patients as compared to health controls. Further, a significant
      association between the STin2.12 allele and OCD, as well as a dominant effect of
      the STin2.12 allele in OCD was seen. Of note, late-onset (>18years) OCD was
      significantly more often seen in association with homozygosis for STin2.12
      allele. No significant associations were observed with different OCD symptom
      dimensions. CONCLUSION: Our results indicate an important influence of the STin2
      polymorphism in OCD, but more studies are warranted to confirm these results.

PMID- 29331880
TI  - Preventive effects of indole-3-carbinol against alcohol-induced liver injury in
      mice via antioxidant, anti-inflammatory, and anti-apoptotic mechanisms: Role of
      gut-liver-adipose tissue axis.
AB  - Indole-3-carbinol (I3C), found in Brassica family vegetables, exhibits
      antioxidant, anti-inflammatory, and anti-cancerous properties. Here, we aimed to
      evaluate the preventive effects of I3C against ethanol (EtOH)-induced liver
      injury and study the protective mechanism(s) by using the well-established
      chronic-plus-binge alcohol exposure model. The preventive effects of I3C were
      evaluated by conducting various histological, biochemical, and real-time PCR
      analyses in mouse liver, adipose tissue, and colon, since functional alterations
      of adipose tissue and intestine can also participate in promoting EtOH-induced
      liver damage. Daily treatment with I3C alleviated EtOH-induced liver injury and
      hepatocyte apoptosis, but not steatosis, by attenuating elevated oxidative
      stress, as evidenced by the decreased levels of hepatic lipid peroxidation,
      hydrogen peroxide, CYP2E1, NADPH-oxidase, and protein acetylation with
      maintenance of mitochondrial complex I, II, and III protein levels and
      activities. I3C also restored the hepatic antioxidant capacity by preventing EtOH
      induced suppression of glutathione contents and mitochondrial aldehyde
      dehydrogenase-2 activity. I3C preventive effects were also achieved by
      attenuating the increased levels of hepatic proinflammatory cytokines, including
      IL1beta, and neutrophil infiltration. I3C also attenuated EtOH-induced gut
      leakiness with decreased serum endotoxin levels through preventing EtOH-induced
      oxidative stress, apoptosis of enterocytes, and alteration of tight junction
      protein claudin-1. Furthermore, I3C alleviated adipose tissue inflammation and
      decreased free fatty acid release. Collectively, I3C prevented EtOH-induced liver
      injury via attenuating the damaging effect of ethanol on the gut-liver-adipose
      tissue axis. Therefore, I3C may also have a high potential for translational
      research in treating or preventing other types of hepatic injury associated with
      oxidative stress and inflammation.

PMID- 29331883
TI  - Curative distal pancreatectomy in patients with acinar cell carcinoma of pancreas
      diagnosed by endoscopic aspiration via esophago-jejunostomy: A successful case
      report.
AB  - INTRODUCTION: This is a case report on the advances in preoperative endoscopic
      guided fine-needle-aspiration (FNA) diagnosis for pancreatic carcinoma to achieve
      a curative operation even in patients who have a history of total gastrectomy.
      CASE PRESENTATION: A 65-year-old man, who underwent total gastrectomy for gastric
      cancer 13 years ago, had discomfort in the left lateral abdomen. A 3-cm
      hypovascular mass accompanying a large distal pseudocyst in the pancreatic tail
      was observed on computed tomography. Endoscopic ultrasonography via elevation of
      the jejunal loop on esophago-jejunostomy also revealed similar lesions, and FNA
      for the proximal-side hypoechoic mass was successful. The cytological diagnosis
      with immunohistochemistry was acinar cell carcinoma of the pancreas. Distal
      pancreatectomy with splenectomy was successfully performed. Histology of the
      resected specimen also showed the acinar cell carcinoma, similar with
      preoperative cytology, which involved the splenic vein and had extra-pancreatic
      extension but no lymph node metastasis. The tumor stage was IIA by the 2009 UICC
      classification. He had no tumor relapse on imaging follow-up until 12 months
      after the operation. DISCUSSION: There have been marked technical advancements in
      endoscopic ultrasonography-guided diagnosis, including FNA, even in patients with
      prior digestive tract surgery. However, the risk of complication is still a
      concern. Accurate histological diagnosis is useful in the field of pancreatic
      surgery, especially in cases of rare or small malignant lesions. CONCLUSION:
      Curative pancreatectomy was possible in a case of acinar cell carcinoma, a rare
      pancreatic malignancy, which was diagnosed by preoperative endoscopic FNA
      diagnosis via esophago-jejunostomy after previous total gastrectomy.

PMID- 29331884
TI  - True left-sided gallbladder: A case report and comparison with the literature for
      the different techniques of laparoscopic cholecystectomy for such anomalies.
AB  - INTRODUCTION: True left-sided gallbladder (LSG) is a rare finding that may
      present with symptoms similar to those of a normally positioned gallbladder.
      Moreover, it may be missed by preoperative imaging studies such as ultrasound,
      computed tomography (CT), magnetic resonance imaging (MRI), or endoscopic
      ultrasound. True left-sided gallbladder is a surgical challenge and surgical
      technique may need to be modified for the completion of laparoscopic
      cholecystectomy. PRESENTATION OF CASE: In this case report, we present a case of
      true left-sided gallbladder that produced right-sided abdominal symptoms.
      Ultrasound of the abdomen failed to show the left-sided position of the
      gallbladder. MRI showed the gallbladder located to the left of the ligamentum
      teres underneath segment III of the liver. Intraoperatively, the gallbladder was
      grasped and retracted to the right under the falciform ligament and it was
      removed using classical right-sided ports with no modification to the technique.
      No complications were encountered intraoperatively or postoperatively.
      DISCUSSION: True LSG is a rare anomaly that may present with right-sided symptoms
      like normally positioned gallbladder. It may be missed in preoperative imaging
      studies and can be discovered only intraoperatively. Modification of laparoscopic
      ports, change in patient's position and/or surgeon's position, or conversion to
      open cholecystectomy may be needed for safe removal of the gallbladder.
      CONCLUSION: Classical technique of laparoscopic cholecystectomy is feasible for
      left-sided gallbladder. However, if the anatomy is not clear, modifications of
      the surgical technique may be necessary for the safe dissection of the
      gallbladder.

PMID- 29331885
TI  - Autonomously hyperfunctioning cystic nodule harbouring thyroid carcinoma - Case
      report and literature review.
AB  - INTRODUCTION: Hyperthyroidism is rarely associated with malignancy, but it cannot
      rule out thyroid cancer. Although there is published data describing this
      coexistence, thyroid carcinomas inside autonomously functioning nodules are
      uncommon. PRESENTATION OF CASE: A 49-year-old woman presented with a cervical
      mass, unexplained weight loss and anxiousness, sweating and insomnia. On physical
      examination, she had a palpable left thyroid nodule. Thyroid function tests
      showed suppressed TSH (<0,1 uUI/mL), thyroxine 1,44 ng/dL (normal range 0,70
      1,48) and triiodothyronine 4,33 pg/mL (normal range 1,71-3,71). Ultrasound
      imaging revealed a left lobe, 4 cm partial cystic nodule. 99mTC thyroid
      scintigraphy showed a hyperfunctioning nodule with suppression of the remainder
      parenchyma. Fine-needle aspiration cytology was nondiagnostic (cystic fluid). The
      patient was started on thiamazole 5 mg daily with subsequent normalization of
      thyroid function, but she developed cervical foreign body sensation and a left
      hemithyroidectomy was performed. Histology showed a 4 cm cystic nodule with a
      follicular variant papillary carcinoma and the patient underwent completion
      thyroidectomy, followed by radio-iodine ablation. DISCUSSION: Published
      literature showed an increased prevalence of autonomously functioning nodules,
      harbouring thyroid carcinomas in adults. Papillary carcinoma is the most
      frequently described but the follicular variant is rare. CONCLUSION: Although
      rare, thyroid cancer is not definitively excluded in hyperthyroid patients and it
      should always be considered as differential diagnosis.

PMID- 29331886
TI  - Anti-cancer Effects of HNHA and Lenvatinib by the Suppression of EMT-Mediated
      Drug Resistance in Cancer Stem Cells.
AB  - Anaplastic thyroid cancer (ATC) constitutes less than 2% of total thyroid cancers
      but accounts for 20-40% of thyroid cancer-related deaths. Cancer stem cell drug
      resistance represents a primary factor hindering treatment. This study aimed to
      develop targeted agents against thyroid malignancy, focusing on individual and
      synergistic effects of HNHA (histone deacetylase), lenvatinib (FGFR), and
      sorafenib (tyrosine kinase) inhibitors. Patients with biochemically and
      histologically proven papillary thyroid cancer (PTC) and ATC were included. Cell
      samples were obtained from patients at the Thyroid Cancer Center, Gangnam
      Severance Hospital, Yonsei University College of Medicine, Seoul, Korea. PTC and
      ATC cells were treated with lenvatinib or sorafenib, alone or in combination with
      HNHA. Tumor-bearing mice (10/group) were administered 10 mg/kg lenvatinib (p.o.)
      or 40 mg/kg sorafenib (p.o.), alone or in combination with 25 mg/kg HNHA (i.p.)
      once every three days. Gene expression in patient-derived PTC and ATC cells was
      compared using a microarray approach. Cellular apoptosis and proliferation were
      examined by immunohistochemistry and MTT assays. Tumor volume and cell properties
      were examined in the mouse xenograft model. HNHA-lenvatinib combined treatment
      induced markers of cell cycle arrest and apoptosis and suppressed anti-apoptosis
      markers, epithelial-mesenchymal transition (EMT), and the FGFR signaling pathway.
      Combined treatment induced significant tumor shrinkage in the xenograft model.
      HNHA-lenvatinib combination treatment thus blocked the FGFR signaling pathway,
      which is important for EMT. Treatment with HNHA-lenvatinib combination was more
      effective than either agent alone or sorafenib-HNHA combination. These findings
      have implications for ATC treatment by preventing drug resistance in cancer stem
      cells.

PMID- 29331888
TI  - A Longitudinal Analysis of IDO and PDL1 Expression during Immune- or Targeted
      Therapy in Advanced Melanoma.
AB  - A deepened understanding of the cellular and molecular processes in the tumor
      microenvironment is necessary for the development of precision immunotherapy
      (IT). We simultaneously investigated CD3, PDL1, and IDO by immunohistochemistry
      in paired biopsies from various organs of 43 metastatic melanoma patients treated
      with IT and targeted therapy (TT). Intraindividual biopsies taken after a period
      of weeks to months demonstrate discordant results in 30% of the cases. Overlap of
      IDO and PDL1 increased after therapy. IT only marginally impacted PDL1 expression
      over time in contrast to TT. Standardized repeated assessments of multiple immune
      markers in repeated biopsies will generate detailed insights in melanoma's immune
      evolution and adaption during therapies and might be used to support treatment
      decisions.

PMID- 29331889
TI  - L-ascorbic acid metabolism in an ascorbate-rich kiwifruit (Actinidia. Eriantha
      Benth.) cv. 'White' during postharvest.
AB  - Kiwifruit (Actinidia eriantha Benth.) 'White', a novel cultivar with higher L
      ascorbic acid (AsA) level, is registered in China. Changes in AsA, related
      metabolites, enzymatic activity, and gene expression associated with AsA
      biosynthesis and recycling process were investigated in this paper. The results
      indicated that AsA biosynthesis through L-galactose pathway supplemented by D
      galacturonic acid pathway and AsA recycling collectively contributed to
      accumulating and remaining higher AsA level in kiwifruit cv. 'White' during
      postharvest. Moreover, L-galactose dehydrogenase (GalDH) activity and relative
      expressions of the genes encoding GDP-D-mannose pyrophosphorylase (GMP), L
      galactose-1-P phosphatase (GPP), GDP-L-galactose phosphorylase (GGP), GalDH and D
      galacturonate reductase (GalUR) were important for regulation of AsA
      biosynthesis, and the activity and expression of dehydroascorbate reductase
      (DHAR) were primarily responsible for regulation of AsA recycling in kiwifruit
      'White' during postharvest.

PMID- 29331887
TI  - IDH1R132H Promotes Malignant Transformation of Benign Prostatic Epithelium by
      Dysregulating MicroRNAs: Involvement of IGF1R-AKT/STAT3 Signaling Pathway.
AB  - Risk stratification using molecular features could potentially help distinguish
      indolent from aggressive prostate cancer (PCa). Mutations in isocitrate
      dehydrogenase (IDH) acquire an abnormal enzymatic activity, resulting in the
      production of 2-hydroxyglutarate and alterations in cellular metabolism, histone
      modification, and DNA methylation. Mutant IDH1 has been identified in various
      human malignancies, and IDH1R132H constituted the vast majority of mutational
      events of IDH1. Most recent studies suggested that IDH1 mutations define a
      methylator subtype in PCa. However, the function of IDH1R132H in PCa development
      and progression is largely unknown. In this study, we showed that the prevalence
      of IDH1R132H in Chinese PCa patients is 0.6% (2/336). Of note, IDH1R132H-mutant
      PCa patients lacked other canonical genomic lesions (e.g., ERG rearrangement,
      PTEN deletion) that are common in most other PCa patients. The in vitro
      experiment suggested that IDH1R132H can promote proliferation of benign prostate
      epithelial cell RWPE-1 when under the situation of low cytokine. It could also
      promote migration capacity of RWPE-1 cells. Mechanistically, IDH1R132H was an
      important regulator of insulin-like growth factor 1receptor (IGF1R) by
      downregulating a set of microRNAs (miR-141-3p, miR-7-5p, miR-223-3p). These
      microRNAs were repressed by the alteration of epigenetic modification to decrease
      the enrichment of active marker H3K4me3 or to increase repressive marker H3K27me3
      at their promoters. Collectively, we proposed a novel model for an IDH1R132H
      microRNAs-IGF1R regulatory axis, which might provide insight into the function of
      IDH1R132H in PCa development.

PMID- 29331890
TI  - Deep sequence analysis reveals the ovine rumen as a reservoir of antibiotic
      resistance genes.
AB  - Antibiotic resistance is an increasingly important environmental pollutant with
      direct consequences for human health. Identification of environmental sources of
      antibiotic resistance genes (ARGs) makes it possible to follow their evolution
      and prevent their entry into the clinical setting. ARGs have been found in
      environmental sources exogenous to the original source and previous studies have
      shown that these genes are capable of being transferred from livestock to humans.
      Due to the nature of farming and the slaughter of ruminants for food, humans
      interact with these animals in close proximity, and for this reason it is
      important to consider the risks to human health. In this study, we characterised
      the ARG populations in the ovine rumen, termed the resistome. This was done using
      the Comprehensive Antibiotic Resistance Database (CARD) to identify the presence
      of genes conferring resistance to antibiotics within the rumen. Genes were
      successfully mapped to those that confer resistance to a total of 30 different
      antibiotics. Daptomycin was identified as the most common antibiotic for which
      resistance is present, suggesting that ruminants may be a source of daptomycin
      ARGs. Colistin resistance, conferred by the gene pmrE, was also found to be
      present within all samples, with an average abundance of 800 counts. Due to the
      high abundance of some ARGs (against daptomycin) and the presence of rare ARGs
      (against colistin), we suggest further study and monitoring of the rumen
      resistome as a possible source of clinically relevant ARGs.

PMID- 29331892
TI  - Dynamic probabilistic material flow analysis of nano-SiO2, nano iron oxides, nano
      CeO2, nano-Al2O3, and quantum dots in seven European regions.
AB  - Static environmental exposure assessment models based on material flow analysis
      (MFA) have previously been used to estimate flows of engineered nanomaterials
      (ENMs) to the environment. However, such models do not account for changes in the
      system behavior over time. Dynamic MFA used in this study includes the time
      dependent development of the modelling system by considering accumulation of ENMs
      in stocks and the environment, and the dynamic release of ENMs from nano
      products. In addition, this study also included regional variations in
      population, waste management systems, and environmental compartments, which
      subsequently influence the environmental release and concentrations of ENMs. We
      have estimated the flows and release concentrations of nano-SiO2, nano-iron
      oxides, nano-CeO2, nano-Al2O3, and quantum dots in the EU and six geographical
      sub-regions in Europe (Central Europe, Northern Europe, Southern Europe, Eastern
      Europe, South-eastern Europe, and Switzerland). The model predicts that a large
      amount of ENMs are accumulated in stocks (not considering further
      transformation). For example, in the EU 2040 Mt of nano-SiO2 are stored in the in
      use stock, 80,400 tonnes have been accumulated in sediments and 65,600 tonnes in
      natural and urban soil from 1990 to 2014. The magnitude of flows in waste
      management processes in different regions varies because of differences in waste
      handling. For example, concentrations in landfilled waste are lowest in South
      eastern Europe due to dilution by the high amount of landfilled waste in the
      region. The flows predicted in this work can serve as improved input data for
      mechanistic environmental fate models and risk assessment studies compared to
      previous estimates using static models.

PMID- 29331891
TI  - Global association between ambient air pollution and blood pressure: A systematic
      review and meta-analysis.
AB  - Although numerous studies have investigated the association of ambient air
      pollution with hypertension and blood pressure (BP), the results were
      inconsistent. We performed a comprehensive systematic review and meta-analysis of
      these studies. Seven international and Chinese databases were searched for
      studies examining the associations of particulate (diameter<2.5 MUm (PM2.5), 2.5
      10 MUm (PM2.5-10) or >10 MUm (PM10)) and gaseous (sulfur dioxide (SO2), nitrogen
      dioxide (NO2), nitrogen oxides (NOx), ozone (O3), carbon monoxide (CO)) air
      pollutants with hypertension or BP. Odds ratios (OR), regression coefficients
      (beta) and their 95% confidence intervals were calculated to evaluate the
      strength of the associations. Subgroup analysis, sensitivity analysis, and meta
      regression analysis were also conducted. The overall meta-analysis showed
      significant associations of long-term exposures to PM2.5 with hypertension (OR =
      1.05), and of PM10, PM2.5, and NO2 with DBP (beta values: 0.47-0.86 mmHg). In
      addition, short-term exposures to four (PM10, PM2.5, SO2, NO2), two (PM2.5 and
      SO2), and four air pollutants (PM10, PM2.5, SO2, and NO2), were significantly
      associated with hypertension (ORs: 1.05-1.10), SBP (beta values: 0.53-0.75 mmHg)
      and DBP (beta values: 0.15-0.64 mmHg), respectively. Stratified analyses showed a
      generally stronger relationship among studies of men, Asians, North Americans,
      and areas with higher air pollutant levels. In conclusion, our study indicates a
      positive association between ambient air pollution and increased BP and
      hypertension. Geographical and socio-demographic factors may modify the pro
      hypertensive effects of air pollutants.

PMID- 29331893
TI  - Ambient volatile organic compounds (VOCs) in communities of the Athabasca oil
      sands region: Sources and screening health risk assessment.
AB  - An investigation of ambient levels and sources of volatile organic compounds
      (VOCs) and associated public health risks was carried out at two northern Alberta
      oil sands communities (Fort McKay and Fort McMurray located < 25 km and >30 km
      from oil sands development, respectively) for the period January 2010-March 2015.
      Levels of total detected VOCs were comparatively similar at both communities
      (Fort McKay: geometric mean = 22.8 MUg/m3, interquartile range, IQR = 13.8-41
      MUg/m3); (Fort McMurray: geometric mean = 23.3 MUg/m3, IQR = 12.0-41 MUg/m3). In
      general, methanol (24%-50%), alkanes (26%-32%) and acetaldehyde (23%-30%) were
      the predominant VOCs followed by acetone (20%-24%) and aromatics (~9%). Mean and
      maximum ambient concentrations of selected hazardous VOCs were compared to health
      risk screening criteria used by United States regulatory agencies. The Positive
      matrix factorization (PMF) model was used to identify and apportion VOC sources
      at Fort McKay and Fort McMurray. Five sources were identified at Fort McKay,
      where four sources (oil sands fugitives, liquid/unburned fuel,
      ethylbenzene/xylene-rich and petroleum processing) were oil sands related
      emissions and contributed to 70% of total VOCs. At Fort McMurray six sources were
      identified, where local sources other than oil sands development were also
      observed. Contribution of aged air mass/regional transport including biomass
      burning emissions was ~30% of total VOCs at both communities. Source-specific
      carcinogenic and non-carcinogenic risk values were also calculated and were below
      acceptable and safe levels of risk, except for aged air mass/regional transport
      (at both communities), and ethylbenzene/xylene-rich (only at Fort McMurray).

PMID- 29331894
TI  - Pharmaceutical concentration variability at sewage treatment plant outlets
      dominated by hydrology and other factors.
AB  - A study was conducted in which the effluent at four small to medium sized sewage
      treatment plants (STP) in North Rhine-Westphalia, Germany was monitored for three
      pharmaceutical compounds (carbamazepine, diclofenac, metoprolol) over a period of
      four years. Grab sampling and auto sampling campaigns were accomplished with
      respect to various weather conditions in the catchment area. Flow volumes and
      hydraulic retention times (HRT) from various sampling dates which provide
      information on processes causing emission changes were additionally taken into
      account. Monitoring results showed that concentration scattering in the effluent
      is related to HRT in the sewage treatment plants. Dilution effects following rain
      events in the catchment area were analysed for the three investigated substances.
      Short-term emission changes explained by dilution only could be well determined
      by the mathematical relation between discharge and concentration, and for
      carbamazepine to be solely determined by the dilution effects at all HRTs. For
      metoprolol, a clear decrease in concentrations was observed at HRTs above 80 h,
      and a significant contribution of biodegradation was supported by independent
      biodegradation tests. For three out of the four STPs, a decrease in
      concentrations of diclofenac was observed at hydraulic retention times above 80
      h, indicating removal, whereas the relationship between concentration and HRT of
      the other STP could be explained by dilution only. The study shows that emissions
      can vary with weather conditions, hampering the assessment of emissions and
      estimation of concentrations in surface waters from generic removal rates only.
      Furthermore, it illustrates the importance of HRT of rather stable substances in
      wastewater treatment.

PMID- 29331895
TI  - Reduction in soil N2O emissions by pH manipulation and enhanced nosZ gene
      transcription under different water regimes.
AB  - Several studies have been carried out to examine nitrous oxide (N2O) emissions
      from agricultural soils in the past. However, the emissions of N2O particularly
      during amelioration of acidic soils have been rarely studied. We carried out the
      present study using a rice-rapeseed rotation soil (pH 5.44) that was amended with
      dolomite (0, 1 and 2 g kg-1 soil) under 60% water filled pore space (WFPS) and
      flooding. N2O emissions and several soil properties (pH, NH4+N, NO3--N, and nosZ
      gene transcripts) were measured throughout the study. The increase in soil pH
      with dolomite application triggered soil N transformation and transcripts of nosZ
      gene controlling N2O emissions under both water regimes (60% WFPS and flooding).
      The 60% WFPS produced higher soil N2O emissions than that of flooding, and
      dolomite largely reduced N2O emissions at higher pH under both water regimes
      through enhanced transcription of nosZ gene. The results suggest that
      ameliorating soil acidity with dolomite can substantially mitigate N2O emissions
      through promoting nosZ gene transcription.

PMID- 29331896
TI  - Environmentally available hexavalent chromium in soils and sediments impacted by
      dispersed fly ash in Sarigkiol basin (Northern Greece).
AB  - Hexavalent chromium is one of the most toxic and carcinogenic species known and
      can be released into the environment from several sources. In Sarigkiol basin (N
      Greece) the presence of Cr(VI) in soil, sediments and groundwater may originate
      from both natural (ophiolitic rocks and their weathering products) and
      anthropogenic (dispersed fly ash produced from lignite power plants) sources. In
      this study, the distribution of contents and origin of environmentally available
      Cr(VI) in soils, sediments, regoliths and fly ash of Sarigkiol basin is
      presented. Detailed geochemical and mineralogical studies were performed on soil
      samples (up to 1 m) and regoliths, while leaching tests were also applied to
      fresh and old fly ash samples. Leachable chromium from soil and sediment samples
      generally increased with depth and the highest concentrations were observed near
      to the power plant of Agios Dimitrios. The speciation of chromium in leachates
      revealed that Cr(VI) concentrations accounted for more than 96% of total Cr.
      Leaching tests of regoliths established that the natural contribution of Cr(VI)
      is up to 14 MUg kg-1. Therefore, the measurement of higher concentrations (up to
      80 MUg kg-1) of environmentally available Cr(VI) in soils and sediments can be
      attributed to the impact/presence of dispersed fly ash in the soils and sediments
      of the same area. This was also supported by the low correlation recorded between
      environmentally available chromium and Cr-bearing minerals (mainly serpentine and
      talc). The influenced zone is located in the eastern part of the basin near the
      local power plant and surrounds an open conveyor belt that transfers fly ash to
      an open temporary storage pit. This zone overlies an unconfined porous aquifer
      thus explaining the elevated concentrations of Cr(VI) in groundwater (up to 120
      MUg L-1) previously reported in this area.

PMID- 29331897
TI  - A framework for delineating the regional boundaries of PM2.5 pollution: A case
      study of China.
AB  - Fine particulate matter (PM2.5) pollution has been a major issue in many
      countries. Considerable studies have demonstrated that PM2.5 pollution is a
      regional issue, but little research has been done to investigate the regional
      extent of PM2.5 pollution or to define areas in which PM2.5 pollutants interact.
      To allow for a better understanding of the regional nature and spatial patterns
      of PM2.5 pollution, This study proposes a novel framework for delineating
      regional boundaries of PM2.5 pollution. The framework consists of four steps,
      including cross-correlation analysis, time-series clustering, generation of
      Voronoi polygons, and polygon smoothing using polynomial approximation with
      exponential kernel method. Using the framework, the regional PM2.5 boundaries for
      China are produced and the boundaries define areas where the monthly PM2.5 time
      series of any two cities show, on average, more than 50% similarity with each
      other. These areas demonstrate straightforwardly that PM2.5 pollution is not
      limited to a single city or a single province. We also found that the PM2.5 areas
      in China tend to be larger in cold months, but more fragmented in warm months,
      suggesting that, in cold months, the interactions between PM2.5 concentrations in
      adjacent cities are stronger than in warmer months. The proposed framework
      provides a tool to delineate PM2.5 boundaries and identify areas where PM2.5
      pollutants interact. It can help define air pollution management zones and assess
      impacts related to PM2.5 pollution. It can also be used in analyses of other air
      pollutants.

PMID- 29331898
TI  - Coadsorption and subsequent redox conversion behaviors of As(III) and Cr(VI) on
      Al-containing ferrihydrite.
AB  - Naturally occurring ferrihydrite often contains various impurities, and Al is one
      of the most prominent impurities. However, little is known about how these
      impurities impact the physical and chemical properties of ferrihydrite with
      respect to metal(loid) adsorption. In this study, a series of Al-containing
      ferrihydrites were synthesized and exposed to a mixed solution containing As(III)
      and Cr(VI). The results showed that the two contaminants can be quickly adsorbed
      onto the surface of Al-containing ferrihydrite under acidic and neutral
      conditions. With the increase of Al molar percentage in ferrihydrites from 0 to
      30, the adsorption capacity of As(III) decreased, whereas it increased for
      Cr(VI). On the other hand, with the increase of pH value from 3.0 to 11.0, the
      decreasing rate of As(III) was accelerated first, then slowed down, whereas the
      Cr(VI) decreasing rate slowed down dramatically. X-ray diffraction (XRD),
      Brunauer-Emmett-Teller (BET) analysis method, transmission electron microscopy
      (TEM) analysis, energy dispersive spectroscopy (EDS) mapping, Attenuated Total
      Reflectance Fourier Transform Infrared Spectroscopy (ATR-FTIR), and X-ray
      photoelectron spectroscopy (XPS) were employed to characterize Al-containing
      ferrihydrite. Interestingly, it was found that the redox transformation occurred
      between As(III) and Cr(VI) after the two contaminants were coadsorbed onto the
      surface of Al-containing ferrihydrite. The oxidation of As(III) to As(V) and
      reduction of Cr(VI) to Cr(III) would greatly lower the environmental hazard of
      the As(III) and Cr(VI).

PMID- 29331899
TI  - The speed of memory errors shows the influence of misleading information: Testing
      the diffusion model and discrete-state models.
AB  - In this report, we evaluate single-item and forced-choice recognition memory for
      the same items and use the resulting accuracy and reaction time data to test the
      predictions of discrete-state and continuous models. For the single-item trials,
      participants saw a word and indicated whether or not it was studied on a previous
      list. The forced-choice trials had one studied and one non-studied word that both
      appeared in the earlier single-item trials and both received the same response.
      Thus, forced-choice trials always had one word with a previous correct response
      and one with a previous error. Participants were asked to select the studied word
      regardless of whether they previously called both words "studied" or "not
      studied." The diffusion model predicts that forced-choice accuracy should be
      lower when the word with a previous error had a fast versus a slow single-item
      RT, because fast errors are associated with more compelling misleading memory
      retrieval. The two-high-threshold (2HT) model does not share this prediction
      because all errors are guesses, so error RT is not related to memory strength. A
      low-threshold version of the discrete state approach predicts an effect similar
      to the diffusion model, because errors are a mixture of responses based on
      misleading retrieval and guesses, and the guesses should tend to be slower.
      Results showed that faster single-trial errors were associated with lower forced
      choice accuracy, as predicted by the diffusion and low-threshold models.

PMID- 29331900
TI  - A catalytic and dual recycling amplification ATP sensor based on target-driven
      allosteric structure switching of aptamer beacons.
AB  - Abnormal concentrations of ATP are associated with many diseases and cancers, and
      quantitative detection of ATP is thus of great importance for disease diagnosis
      and prognosis. In the present work, we report a new dual recycling amplification
      sensor integrated with catalytic hairpin assembly (CHA) to achieve high
      sensitivity for fluorescent detection of ATP. The association of the target ATP
      with the aptamer beacons causes the allosteric structure switching of the aptamer
      beacons to expose the toehold regions, which hybridize with and unfold the
      fluorescently quenched hairpin signal probes (HP1) to recycle the target ATP and
      to trigger CHA between HP1 and the secondary hairpin probes (HP2) to form HP1/HP2
      duplexes. Due to the recycling amplification, the presence of ATP leads to the
      formation of many HP1/HP2 duplexes, generating dramatically amplified fluorescent
      signals for sensitive detection of ATP. Under optimal experimental conditions,
      our sensor linearly responds to ATP in the range from 25 to 600nM with a
      calculated detection limit of 8.2nM. Furthermore, the sensor shows a high
      selectivity and can also be used to detect ATP in human serums to realize its
      application for real samples. With the distinct advantage of significant signal
      amplification without the involvement of any nanomaterial and enzyme, the
      developed sensor thus holds great potential for simple and sensitive detection of
      different small molecules and proteins.

PMID- 29331901
TI  - An ultrasensitive detection of miRNA-155 in breast cancer via direct
      hybridization assay using two-dimensional molybdenum disulfide field-effect
      transistor biosensor.
AB  - MicroRNAs (miRNAs), critical biomarkers of acute and chronic diseases, play key
      regulatory roles in many biological processes. As a result, robust assay
      platforms to enable an accurate and efficient detection of low-level miRNAs in
      complex biological samples are of great significance. In this work, a label-free
      and direct hybridization assay using molybdenum disulfide (MoS2) field-effect
      transistor (FET) biosensor has been developed for ultrasensitive detection of
      miRNA-155 as a breast cancer biomarker in human serum and cell-line samples.
      MoS2, the novel 2D layered material with excellent physical and chemical
      properties, was prepared through sequential solvent exchange method and was used
      as an active channel material. MoS2 was comprehensively characterized by
      spectroscopic and microscopic methods and it was applied for fabrication of FET
      device by drop-casting MoS2 flacks suspension onto the FET surface. MoS2 FET
      device showed a relatively low subthreshold swing of 48.10mV/decade and a high
      mobility of 1.98 * 103cm2V-1s-1. Subsequently, probe miRNA-155 strands were
      immobilized on the surface of the MoS2 FET device. Under optimized conditions
      detection limit of 0.03fM and concentration range 0.1fM to 10nM were achieved.
      The developed biosensor not only was capable to identification of fully matched
      versus one-base mismatch miRNA-155 sequence, but also it could detect target
      miRNA-155 in spiked real human serum and extracts from human breast cancer cell
      line samples. This approach paves a way for label-free, early detection of miRNA
      as a biomarker in cancer diagnostics with very high sensitivity and good
      specificity, thus offering a significant potential for clinical application.

PMID- 29331902
TI  - The use of interprofessional learning and simulation in undergraduate nursing
      programs to address interprofessional communication and collaboration: An
      integrative review of the literature.
AB  - OBJECTIVE: To identify how simulation and interprofessional learning are used
      together in undergraduate nursing programs and undertaken in schools of nursing
      to address interprofessional communication and collaboration. DESIGN: An
      integrative literature review. DATA SOURCES: The databases CINAHL, ProQuest,
      PubMed, Scopus, PsycInfo and Science Direct were searched to identify articles
      from 2006 to 2016 that reported on the use of IPL and simulation together in
      undergraduate nursing education. REVIEW METHOD: Whittemore and Knafl's five step
      process was used to guide the integrative review of quantitative and qualitative
      literature. Only peer reviewed articles written in English that addressed
      undergraduate nursing studies, were included in the review. Articles that did not
      aim to improve communication and collaboration were excluded. All articles
      selected were examined to determine their contribution to interprofessional
      learning and simulation in undergraduate nursing knowledge. RESULTS: The
      faculties of nursing used interprofessional learning and simulation in
      undergraduate nursing programs that in some cases were connected to a specific
      course. A total of nine articles, eight research papers and one narrative report,
      that focused on collaboration and communication were selected for this review.
      Studies predominantly used nursing and medical student participants. None of the
      included studies identified prior student experience with interprofessional
      learning and simulation. Four key themes were identified: communication,
      collaboration/teamwork, learning in practice and understanding of roles, and
      communication. CONCLUSION: This review highlights the identified research
      relating to the combined teaching strategy of interprofessional learning and
      simulation that addressed communication and collaboration in undergraduate
      nursing programs. Further research into the implementation of interprofessional
      learning and simulation may benefit the emergent challenges. Information drawn
      from this review can be used in informing education and educational development
      in the future.

PMID- 29331903
TI  - Rapid structure prediction by HPLC-ESI-MSn of twenty-five polyoxypregnane
      tetraglycosides from Dregea sinensis with NMR confirmation of eight structures.
AB  - Dregea sinensis Hemsl is an important herbal medicine in the Dai nationality of
      China. Its prominent clinical application has generated interest in the
      polyoxypregnane glycosides of the plant. This paper describes an extension of
      previous research on the polyoxypregnane di- and triglycosides of D. sinensis,
      aiming at identifying related tetraglycosides. On the basis of HPLC-ESI-MSn
      analysis in positive mode, twenty-five previously undescribed polyoxypregnane
      tetraglycosides were characterized (regarding molecular masses and fragmentation
      in MSn) from an ethyl acetate fraction that was not previously investigated.
      Guided by MSn fragmentation and known structures of related di- and triglycosides
      from D. sinensis, tentative structures were predicted from the MS data. In order
      to test the predictions, eight of the glycosides were isolated and their
      structures were elucidated by 1D and 2D NMR methods, confirming the tentative
      predictions. Finally, the cytotoxicity of the isolates was evaluated on several
      human cell lines with little effect in general, even though slight inhibitory
      effects of four polyoxypregnane glycosides were detected at 10 MUM against the
      human leukemia cell line HL-60.

PMID- 29331904
TI  - Anthocyanins in perilla plants and dried leaves.
AB  - High-quality perilla leaves are purple on upper and lower surfaces and have a
      good aroma. The Japanese Pharmacopoeia specifies the content of essential oils in
      perilla leaves but not that of anthocyanins. Several reports have described the
      chemical species of anthocyanins in red perilla, but a complete analysis of
      anthocyanins in perilla has not been reported. In this study, the anthocyanins in
      the leaves of cultivated and wild species of perilla and those in commercially
      available perilla herbs were studied. Red perilla and most P. citriodora strains
      accumulate cyanidin derivatives that differ in the acyl group on the glucose
      moiety at the 3-O- and 5-O-positions of the anthocyanins. Several strains of P.
      citriodora contain cyanidin derivatives that are different from those in red
      perilla and most P. citriodora species. Green perilla and wild species other than
      P. citriodora do not contain foliar anthocyanins. The anthocyanins in
      commercially available perilla herbs and natural dyes made from red perilla were
      in agreement with those in fresh red perilla leaves and most P. citriodora
      samples. The amounts and types of anthocyanins were not associated with place of
      cultivation, although some changes occurred due to degradation during storage.
      These results provide clues regarding the biosynthesis of anthocyanins in perilla
      and the evolution of red perilla. The characteristics and stability of
      anthocyanins are discussed.

PMID- 29331905
TI  - Macrophage phenotype switch by sequential action of immunomodulatory cytokines
      from hydrogel layers on titania nanotubes.
AB  - Inflammatory response occurring between tissues and implants after implantation
      has attracted increasing attention because it can cause local tissue necrosis and
      even implant failure. Macrophages play a key role in all stages of inflammation.
      Pro-inflammatory (M1) and anti-inflammatory (M2) macrophages comprise two main
      phenotypes and the switch from M1 to M2 at specific time points is important for
      wound healing and tissue regeneration. Therefore, we hypothesized that
      biomaterial systems capable of facilitating macrophage phenotype switching should
      attenuate inflammation and enhance healing. To this end, a system of double
      hydrogel layers on titania nanotubes (TNT) was prepared as reservoir to modulate
      the release of interleukin-4 (IL-4) and interferon-gamma (IFN-gamma). In this
      system, IL-4, an anti-inflammatory cytokine, was loaded in TNT and IFN-gamma, a
      pro-inflammatory cytokine, was located between two hydrogel layers of
      chitosan/beta-glycerophosphate disodium and carboxymethyl chitosan/genipin. IFN
      gamma released rapidly in 3 days, whereas IL-4 exhibited a sustained release
      profile. In culture with mesenchymal stem cells and macrophages, this system
      displayed good cytocompatibility and significantly promoted cell proliferation.
      Macrophage phenotype switch was determined by ELISA, FACS and PCR. The results
      manifested that IFN-gamma released from the system stimulated switching of
      macrophages to M1 in 3 days, whereas sustained release of IL-4 polarized
      macrophages to M2 after 4 days. This system can modulate macrophage phenotype
      switching from M1 to M2 by sequential action of the two cytokines, and might be
      used to research immune response between tissues and implants. The present study
      also provided a novel strategy for designing functional biomaterials.

PMID- 29331906
TI  - Strontium Hydroxyapatite scaffolds engineered with stem cells aid
      osteointegration and osteogenesis in osteoporotic sheep model.
AB  - Osteoporotic fracture healing is an orthopaedic challenge due to excessive bone
      resorption and impaired osteogenesis. Majority of current treatment strategies
      focus on regulating bone resorption and the potential application of Mesenchymal
      Stem Cells (MSCs) in promoting osteogenesis has not been explored much.
      Furthermore, the present study has put forth a novel approach, wherein the
      synergistic action of Strontium (Sr) and MSCs in a single implant may facilitate
      osteoporotic bone healing. Strontium Hydroxyapatite (SrHA) synthesized by wet
      precipitation was fabricated into tissue engineered Strontium incorporated
      Hydroxyapatite (cSrHA) using sheep adipose tissue derived MSCs (ADMSCs).
      Porosity, radiopacity and cytocompatibility of SrHA scaffolds were found
      appropriate for orthopaedic applications. cSrHA scaffolds exhibited an in vitro
      Alkaline Phosphatase activity of 20 MUmol pnp/30 min comparable to that of
      Hydroxyapatite (HA) - control scaffold, proving its osteogenic efficacy.
      Implantation studies in sheep osteoporotic model depicted enhanced osteogenic
      ability with mature lamellar bone formation in cSrHA implanted group, compared to
      bare HA, SrHA and tissue engineered HA implanted groups. Histomorphometry data
      substantiated improved osteogenesis on par with material resorption, as cSrHA
      implanted group exhibited highest regeneration ratio of 0.38 +/- 0.05. Density
      histograms from micro CT further signified the enhanced osteointegrative ability
      of cSrHA implants. Results of the study depicted the therapeutic potential of
      cSrHA in osteoporotic bone healing and proposes the use of allogenic ADMSCs for
      fabricating "Off the Shelf Tissue Engineered Products".

PMID- 29331907
TI  - Applying ultraviolet/persulfate (UV/PS) pre-oxidation for controlling
      ultrafiltration membrane fouling by natural organic matter (NOM) in surface
      water.
AB  - Membrane fouling is a recognized obstacle for the application of ultrafiltration
      (UF) for drinking water treatment. In this study, ultraviolet/persulfate (UV/PS)
      oxidation was employed as a pretreatment to control membrane fouling caused by
      natural organic matter (NOM) in surface water. The effects of UV/PS pretreatment
      on amounts and characteristics of NOM were investigated in terms of dissolved
      organic carbon, fluorescent spectrum, molecular weight distribution and
      hydrophobicity. UF membrane fouling during filtration of raw and pre-oxidized
      water was compared with transmembrane pressure development, and the fouled
      membranes were further characterized using scanning electron microscopy (SEM) and
      Fourier transform infrared spectroscopy (FTIR). The results indicate that NOM was
      considerably degraded and partially mineralized (~58%) by UV/PS pretreatment at a
      PS dose not exceeding 0.6 mM and a UV irradiation time within 120 min, which was
      attributed to the generation of sulfate and hydroxyl radicals. The fluorescent
      compounds in NOM were almost completely degraded (>98%) by the UV/PS pretreatment
      at a PS dose of 0.4 mM, except for tyrosine-like proteins (~80%). Moreover, UV/PS
      pretreatment decreased the ratio of macromolecular compounds and increased the
      hydrophilic fractions, resulting in reduced NOM adhesion to the membrane. Hence,
      irreversible fouling by NOM was significantly retarded (~75%) by the UV/PS
      pretreatment due to reduction in NOM, and more importantly by preferential
      degradation of fluorescent, macromolecular and hydrophobic compounds. Fouling
      control performance was considerably improved at increased PS doses and extended
      UV irradiation time.

PMID- 29331908
TI  - Electricity production and phosphorous recovery as struvite from synthetic
      wastewater using magnesium-air fuel cell electrocoagulation.
AB  - This research was based on the investigation of a major principle, regarding the
      effects of NaCl and KH2PO4 concentrations on struvite recovery, with electricity
      production using magnesium-air fuel cell electrocoagulation, in accordance with
      the concentration of phosphorous and chloride. The weight ratio of N:P in the
      synthetic wastewater was in the range of 1.2-21. The concentration of NH4Cl was
      fixed at 0.277 M (approximately 3888 ppm as NH3-N and 5000 ppm as NH4), while PO4
      P was in the range of 0.006-0.1 M. In addition, the concentrations of NaCl as
      electrolyte were 0, 0.01, and 0.1 M. Phosphate removal increased linearly with
      the Mg:P ratio, up to approximately 1.1 mol mol-1, irrespective of the initial
      concentrations of phosphate and NaCl. The one-to-one reaction as mole ratio
      between phosphate and the dissolved Mg ions resulted in phosphate removal, with
      the production of a one-to-one magnesium/phosphate mineral, such as struvite. The
      average removal rate of phosphorous in experiments without a dose of NaCl was
      4.19 mg P cm-2 h-1, which was lower than the relative values of 5.35 and 4.77 mg
      P cm-2 h-1, in experiments with 0.01 and 0.1 M NaCl. The dissolution rate of Mg
      with electro-oxidation determined the rate of phosphorous removal with struvite
      recovery. The average removal rates of phosphorous with dose concentrations of
      0.006, 0.01 and 0.02 M KH2PO4 were 4.02, 5.54, 6.9 mg P cm-2 h-1, respectively,
      which increased with the increase in KH2PO4 dose. However, in experiments with a
      dose of 0.05 and 0.1 M KH2PO4, the average removal rates of phosphorous decreased
      to 4.84 and 2.51, respectively. The maximum power densities in the electrolyte
      mixture of 0.05 M KH2PO4/0.277 M NH4Cl, 0.01 M NaCl/0.05 M KH2PO4/0.277 M NH4Cl,
      and 0.1 NaCl/0.05 KH2PO4/0.277 M NH4Cl were 25.1, 26.4, and 33.2 W/m2,
      respectively. The increase in the NaCl dose concentration resulted in an increase
      in the maximum power density and current density. A dose above 0.05 M KH2PO4
      resulted in the decrease of the maximum power densities. However, when the dose
      was below 0.05 M KH2PO4, the maximum power density increased with the increase in
      KH2PO4 dose.

PMID- 29331909
TI  - Linking composition of extracellular polymeric substances (EPS) to the physical
      structure and hydraulic resistance of membrane biofilms.
AB  - The effect of extracellular polymeric substances (EPS) on the meso-scale physical
      structure and hydraulic resistance of membrane biofilms during gravity driven
      membrane (GDM) filtration was investigated. Biofilms were developed on the
      surface of ultrafiltration membranes during dead-end filtration at ultra-low
      pressure (70 mbar). Biofilm EPS composition (total protein, polysaccharide and
      eDNA) was manipulated by growing biofilms under contrasting nutrient conditions.
      Nutrient conditions consisted of (i) a nutrient enriched condition with a
      nutrient ratio of 100:30:10 (C: N: P), (ii) a phosphorus limitation (C: N: P
      ratio: 100:30:0), and (iii) a nitrogen limitation (C: N: P ratio: 100:0:10). The
      structure of the biofilm was characterised at meso-scale using Optical Coherence
      Tomography (OCT). Biofilm composition was analysed with respect to total organic
      carbon, total cellular mass and extracellular concentrations of proteins,
      polysaccharides, and eDNA. 2D-confocal Raman mapping was used to characterise the
      functional group composition and micro-scale distribution of the biofilms EPS.
      Our study reveals that the composition of the EPS matrix can determine the meso
      scale physical structure of membrane biofilms and in turn its hydraulic
      resistance. Biofilms grown under P limiting conditions were characterised by
      dense and homogeneous physical structures with high concentrations of
      polysaccharides and eDNA. Biofilm grown under nutrient enriched or N limiting
      conditions were characterised by heterogeneous physical structures with lower
      concentrations of polysaccharides and eDNA. For P limiting biofilms, 2D-confocal
      Raman microscopy revealed a homogeneous spatial distribution of anionic
      functional groups in homogeneous biofilm structures with higher polysaccharide
      and eDNA concentrations. This study links EPS composition, physical structure and
      hydraulic resistance of membrane biofilms, with practical relevance for the
      hydraulic performances of GDM ultrafiltration.

PMID- 29331910
TI  - Review of synthetic human faeces and faecal sludge for sanitation and wastewater
      research.
AB  - Investigations involving human faeces and faecal sludge are of great importance
      for urban sanitation, such as operation and maintenance of sewer systems, or
      implementation of faecal sludge management. However, working with real faecal
      matter is difficult as it not only involves working with a pathogenic, malodorous
      material but also individual faeces and faecal sludge samples are highly
      variable, making it difficult to execute repeatable experiments. Synthetic faeces
      and faecal sludge can provide consistently reproducible substrate and alleviate
      these challenges. A critical literature review of simulants developed for various
      wastewater and faecal sludge related research is provided. Most individual
      studies sought to develop a simulant representative of specific physical,
      chemical, or thermal properties depending on their research objectives. Based on
      the review, a suitable simulant can be chosen and used or further developed
      according to the research needs. As an example, the authors present such a
      modification for the development of a simulant that can be used for investigating
      the motion (movement, settling and sedimentation) of faeces and their physical
      and biological disintegration in sewers and in on-site sanitation systems.

PMID- 29331911
TI  - Enhanced photocatalytic degradation of sulfamethoxazole by zinc oxide
      photocatalyst in the presence of fluoride ions: Optimization of parameters and
      toxicological evaluation.
AB  - The presence of antibiotics in water bodies has received increasing attention
      since they are continuously introduced and detected in the environment and may
      cause unpredictable environmental hazards and risks. The photocatalytic
      degradation of sulfamethoxazole (SMX) by ZnO in the presence of fluoride ions (F
      ZnO) was evaluated. The effects of operating parameters on the efficiency of SMX
      removal were investigated by using response surface methodology (RSM). Under the
      optimum condition, i.e. photocatalyst dosage = 1.48 g/L, pH 4.7, airflow rate =
      2.5 L/min and the concentration of fluoride ions = 2.505 mM, about 97% SMX
      removal was achieved by F-ZnO after 30 min of reaction. The mechanism of
      reactions, COD removal efficiency and reaction kinetics were also investigated
      under optimum operating conditions. In addition, about 85% COD reduction was
      obtained after 90 min photocatalytic reaction. The pseudo-first-order kinetics
      rate constants for the photodegradation of SMX were found to be 0.099, 0.058 and
      0.048 min-1 by F-ZnO, ZnO and TiO2 (P25), respectively. The figure-of-merit
      electrical energy per order (EEO) was used for estimating the electrical energy
      efficiency, which was shown to be considerably lower than the energy consumption
      for the reported research on removal of SMX by photocatalytic degradation under
      UV irradiation. Toxicity assays were conducted by measuring the inhibition
      percentage (PI) towards E. coli bacteria strain and by agar well diffusion
      method. The results showed that after 30 min of reaction, the toxicity of the
      treated solutions by all photocatalysts fell within the non-toxic range; however,
      the reduction in toxicity by F-ZnO was faster than those by ZnO and P25. Despite
      the positive effects of surface fluorination of ZnO on the SMX and COD removal
      and reaction kinetics, its lower stability compared to ZnO and P25 in the
      repeated experiments gave rise to some doubts about its performance from a
      practical point of view.

PMID- 29331912
TI  - Elucidating the impacts of initial supersaturation and seed crystal loading on
      struvite precipitation kinetics, fines production, and crystal growth.
AB  - To reduce intra-plant nutrient cycling, and recover phosphorus (P) fertilizers
      from nutrient-rich sidestreams, wastewater utilities increasingly elect to employ
      struvite precipitation processes without a clear understanding of the inherent
      tradeoffs associated with specific design and operating decisions. Specifically,
      the impact of reactor conditions on struvite crystallization rate, and
      distribution between formation of fines particles and secondary growth onto large
      diameter seed crystals represent critical knowledge gaps limiting the predictive
      capabilities of existing process models. In this work, the relative impacts of
      initial supersaturation (Si), and seed loading, on P removal kinetics, and
      struvite solids distribution were investigated. In experiments conducted at
      different levels of initial supersaturation (1.7-2.4) and seed loading (0-25 g L
      1), struvite fines represented the majority of phosphate solids formed in 10 of
      12 conditions. While total P removal was dependent on Si, and primarily
      attributed to formation of fines, the concentration of struvite seed granules had
      a significant impact on the rate of P removal. Struvite seed granules increased
      the rate of precipitation by reducing induction time of primary nucleation of
      struvite fines. Secondary crystal growth represented the majority of struvite
      solids formed at high seed loading and low Si, but presented the tradeoff of low
      total removal and low rate of removal. To convey the significance of these
      findings on process modeling, we show how a prominent kinetic model with a first
      order dependency on solid struvite concentration over-predicts P removal rate
      when total mass is dominated by large diameter seeds (0.9 mm). This works reveals
      the critical role of struvite fines in P removal, and highlights the need to
      account for their production and kinetic importance in struvite process design
      and operation.

PMID- 29331913
TI  - Speciation evolution of zinc and copper during pyrolysis and hydrothermal
      carbonization treatments of sewage sludges.
AB  - Thermal and hydrothermal treatments are promising techniques for sewage sludge
      management that can potentially facilitate safe waste disposal, energy recovery,
      and nutrient recovery/recycling. Content and speciation of heavy metals in the
      treatment products affect the potential environmental risks upon sludge disposal
      and/or application of the treatment products. Therefore, it is important to study
      the speciation transformation of heavy metals and the effects of treatment
      conditions. By combining synchrotron X-ray spectroscopy/microscopy analysis and
      sequential chemical extraction, this study systematically characterized the
      speciation of Zn and Cu in municipal sewage sludges and their chars derived from
      pyrolysis (a representative thermal treatment technique) and hydrothermal
      carbonization (HTC; a representative hydrothermal treatment technique).
      Spectroscopy analysis revealed enhanced sulfidation of Zn and Cu by anaerobic
      digestion and HTC treatments, as compared to desulfidation by pyrolysis. Overall,
      changes in the chemical speciation and matrix properties led to reduced mobility
      of Zn and Cu in the treatment products. These results provide insights into the
      reaction mechanisms during pyrolysis and HTC treatments of sludges and can help
      evaluate the environmental/health risks associated with the metals in the
      treatment products.

PMID- 29331914
TI  - Pore diffusion limits removal of monochloramine in treatment of swimming pool
      water using granular activated carbon.
AB  - Overall apparent reaction rates for the removal of monochloramine (MCA) in
      granular activated carbon (GAC) beds were determined using a fixed-bed reactor
      system and under conditions typical for swimming pool water treatment. Reaction
      rates dropped and quasi-stationary conditions were reached quickly. Diffusional
      mass transport in the pores was shown to be limiting the overall reaction rate.
      This was reflected consistently in the Thiele modulus, in the effect of
      temperature, pore size distribution and of grain size on the reaction rates.
      Pores <2.5 times the diameter of the monochloramine molecule were shown to be
      barely accessible for the monochloramine conversion reaction. GACs with a
      significant proportion of large mesopores were found to have the highest overall
      reactivity for monochloramine removal.

PMID- 29331915
TI  - Theory of water treatment by capacitive deionization with redox active porous
      electrodes.
AB  - Capacitive deionization (CDI) for water treatment, which relies on the capture of
      charged species to sustain the electrical double layers (EDLs) established within
      porous electrodes under an applied electrical potential, can be enhanced by the
      chemical attachment of fixed charged groups to the porous electrode electrodes
      (ECDI). It has recently been demonstrated that further improvements in capacity
      and energy storage can be gained by functionalization of the electrode surfaces
      with redox polymers in which the charge on the electrodes can be modulated
      through Faradaic reactions under different cell voltages in a capacitive process
      that can be called "Faradaic CDI" (FaCDI). Here, we extend recent mathematical
      models developed for the characterization of CDI and ECDI systems to incorporate
      the redox mediated contributions by allowing for the variable chemical charges
      generated by reactions in FaCDI. The lumped model developed here assumes the
      spacer channel is well-mixed with uniform electrosorption in each electrode. We
      demonstrate that the salt adsorption performance characterization of the fixed
      chemical charge ECDI and variable chemical charge FaCDI materials can be unified
      within a common theoretical framework based on the point of zero charge (PZC) of
      the electrode material. In the latter case the PZC is determined by the
      equilibrium potentials of the redox couples immobilized on the porous electrodes.
      The new model is able to predict the experimentally observed enhanced and
      inverted performance of CDI cells, and illuminates the benefit of choosing redox
      active materials for water treatment applications. The deionization performance
      of FaCDI cells is shown to be superior to that of CDI and ECDI systems with
      equilibrium adsorption capacities 50-100% higher than attained with CDI systems,
      and at smaller cell voltages, depending on the redox potentials of the Faradaic
      moieties.

PMID- 29331916
TI  - Aerobic exercise is more effective than goal-based exercise for the treatment of
      cognition in Parkinson's disease.
AB  - BACKGROUND: Little is known about how different exercise modalities influence
      cognition in Parkinson's disease (PD). Moreover, the focus of previous
      investigations on examining the effects of exercise mainly on executive functions
      and the exclusion of individuals with cognitive impairment may limit the
      potential to define exercise as a treatment for cognitive decline in PD.
      OBJECTIVE: The aim of this study was to compare the effects of aerobic and goal
      based exercise on five cognitive domains in cognitively normal and impaired
      individuals with PD. METHODS: Seventy-six individuals with PD were randomly
      allocated into three groups: Aerobic, Goal-based, and Control. Participants in
      the exercise groups attended 1-h sessions 3x/week for 12 weeks, while those in
      the Control group carried on with their regular activities. Changes in cognitive
      domains were assessed using paper-based neuropsychological tests. RESULTS:
      Inhibitory control improved only in the Aerobic group (p = .04), irrespective of
      participants cognitive status at baseline. Moreover, participants with cognitive
      impairment in Aerobic group maintained their set-shifting ability, whereas those
      in the Control group were worse at post-test (p = .014). CONCLUSION: This is the
      first study to show that aerobic exercise is more effective than goal-based
      exercise for the treatment of cognition in PD with and without cognitive
      impairment.

PMID- 29331917
TI  - Comparision of photocatalysis and photolysis processes for arsenic oxidation in
      water.
AB  - The oxidation of As(III) to As(V) in aqueous solution was evaluated using
      heterogeneous photocatalysis and photolysis. The influence of TiO2 as catalyst in
      different crystalline (rutile, anatase) and commercial forms was evaluated in a
      batch reactor and an insignificant difference was observed between them. The
      process by photocatalysis reached up to 97% As(III) oxidation and no significant
      difference was observed comparing to results obtained by photolysis. The
      photolysis experiments (UV radiation only), also carried out in a batch system,
      showed a high oxidation rate of As(III) (90% in 20min). The influence of
      different matrices (well water, river water and public water supply) were
      evaluated. Additionally, the effect of As(V) concentration, generated during the
      oxidation process, was studied. Continuous photolysis experiments using only UV
      radiation were performed, resulting in a high As(III) oxidation rate. Using a
      flow rate of 5mLmin-1 and an initial concentration of As(III) 200ugL-1, gave an
      oxidation percentage of As(III) of up to 72%, showing a simple and economical
      alternative to the oxidation step of As(III) to As(V) in the treatment of water
      contaminated with arsenic.

PMID- 29331918
TI  - DNA damage in marine rock oyster (Saccostrea Cucullata) exposed to
      environmentally available PAHs and heavy metals along the Arabian Sea coast.
AB  - Molecular biomarkers are used world wide for quick assessment of the immediate
      effect of environmental pollution on marine ecosystems. Recently, we evaluated
      oxidative stress responses of marine rock oyster, Saccostrea cucullata impacted
      due to polycyclic aromatic hydrocarbons (PAHs) accumulated in their tissues at a
      few sampling sites along the coast of Goa around the region of the Arabian sea
      coast, India (Sarkar et al., 2017). Using a combination of partial alkaline
      unwinding and comet assays, we now report a comprehensive study on the impairment
      of DNA integrity (DI) in S. cucullata due to exposure to environmentally
      available PAHs and also heavy metals (Pb, Cd, Cu, Fe and Mn) along the Arabian
      Sea coast, Goa, India exclusively around the entire coast of Goa. First, we
      determined significant correlation between DI in S. cucullata and the extent of
      exposure to and bioaccumulation of different PAH compounds including 2-3 aromatic
      ring PAHs (R2, 0.95), 4-6 aromatic ring PAHs (R2, 0.85), oxygenated-PAHs (oxy
      PAHs, R2, 0.84) and total PAHs (t-PAHs, R2, 0.98). Second, we observed dose
      dependent decrease in DI in S. cucullata with increasing concentrations of
      different PAH components in oyster tissues. We substantiated our field
      observations with appropriate laboratory controls using benzo[a]pyrene (BaP).
      Third, we performed stepwise multiple regression analyses of different water
      quality parameters including pH, salinity, temperature, dissolved oxygen (DO),
      biochemical oxygen demand (BOD), nitrite (NO2), nitrate (NO3), phosphate (PO4),
      turbidity and also t-PAH-biota, t-PAH-water with DI as the dependent variable.
      Among all these parameters, only four parameters such as t-PAH-biota in
      combination with DO, BOD and NO2 showed significant correlation (R-2 = 0.95) with
      loss in DI in S. cucullata. Based on these results, we created a map indicating
      the percentage of DNA damage in S. cucullata exposed to PAHs and heavy metals at
      each sampling location along the west coast of India around Goa, India.

PMID- 29331919
TI  - Removal of pharmaceutical pollutants from synthetic wastewater using chemically
      modified biomass of green alga Scenedesmus obliquus.
AB  - Pharmaceutical compounds are considered emerging environmental pollutants that
      have a potential harmful impact on environment and human health. In this study,
      the biomass of alga (Scenedesmus obliquus) was modified using alkaline solution,
      and used for the biosorption of tramadol (TRAM) and other pharmaceuticals. The
      adsorption kinetics and isotherms were investigated. The obtained results reveal
      high adsorption capacity of tramadol over modified algal biomass (MAB) after
      45min with removal percentage of 91%. Pseudo-second order model was well fitted
      with the experimental data with correlation coefficient (0.999). Biosorption of
      tramadol on modified algal biomass proceeds with Freundlich isotherm model with
      correlation coefficient (0.942) that emphasized uptake of TRAM by MAB is driven
      by chemisorption. FTIR spectra of MAB before and after the adsorption were
      analyzed; some IR bands were detected with slight shift and low intensity
      suggesting their involving in adsorption. The tramadol biosorption by MAB is a
      chemical process as confirmed by Dubinin-Radushkevich. The adsorption of
      pharmaceutical over MAB is mainly preceded by hydrophilic interactions between
      amino and carbonyl groups in pharmaceutical molecules and hydroxyl and carbonyl
      functional groups on surface of biosorbent. It was emphasized by disappearance O
      H and C-O from biomass IR spectra after adsorption. In matrix of pharmaceutical,
      the recorded adsorption capacities for CEFA, PARA, IBU, TRAM and CIP are 68, 58,
      42, 42 and 39mg/g over MAB at natural pH and MAB dose of 0.5g/L. Furthermore,
      oxygen uptake by bacteria was applied for estimate the toxicity of
      pharmaceutical. The recorded result concluded the efficient reusability of
      modified algal biomass for biosorption of pharmaceuticals, as well only the
      adsorption efficiency decreased by 4.5% after three runs. Subsequently, the
      modified algal biomass is a promising reusable adsorbent for decontamination of
      wastewater from pharmaceuticals.

PMID- 29331920
TI  - Engineering yeast for utilization of alternative feedstocks.
AB  - Realizing the economic benefits of alternative substrates for commodity chemical
      bioproduction typically requires significant metabolic engineering of common
      model organisms, such as Saccharomyces cerevisiae. A growing toolkit is enabling
      engineering of non-conventional yeast that have robust native metabolism for
      xylose, acetate, aromatics, and waste lipids. Scheffersomyces stipitis was
      engineered to produce itaconic acid from xylose. Yarrowia lipolytica produced
      lipids from dilute acetate at over 100g/L. Cutaneotrichosporon oleaginosus was
      engineered to produce omega-3 fatty acids and recently was shown to accumulate
      nearly 70% lipids when grown on aromatics as a carbon source. Further improvement
      to toolkits for genetic engineering of non-conventional yeast will enable future
      development of alternative substrate conversion to biochemicals.

PMID- 29331921
TI  - Cyclotron production of 99mTc: Comparison of known separation technologies for
      isolation of 99mTc from molybdenum targets.
AB  - Intensive efforts were undertaken during the last few decades for the separation
      of cyclotron-produced 99mTc from 99Mo and new papers have been published on this
      topic since the last review [1]. In the future the cyclotron-based methods can
      replace reactor-based technology in producing this medical radioisotope and the
      nuclear reaction 100Mo(p,2n)99mTc appears to be the most worthwhile approach. New
      ways of producing of 99mTc require efficient separation methods. Several
      strategies for separation of 99mTc from 99Mo have been already developed. The
      advantages, disadvantages and technical challenges toward application potential
      of investigated methods to separate 99mTc from irradiated 100Mo target are
      discussed. These methods include column chromatography, solvent extraction,
      chemical precipitation and thermochromatography.

PMID- 29331922
TI  - Minimum alveolar concentration: Key concepts and a review of its pharmacological
      reduction in dogs. Part 1.
AB  - OBJECTIVE: To outline the major components of the minimum alveolar concentration
      (MAC) and review the literature in regard to pharmacological manipulation of the
      MAC of halothane, isoflurane, sevoflurane, enflurane, and desflurane in dogs. The
      pharmacologic agents included are alpha-2 agonists, benzodiazepines, propofol,
      maropitant, opioids, lidocaine, acepromazine, non-steroidal anti-inflammatory
      agents, and NMDA antagonists. Part 1 will focus on summarizing the relevance,
      measurement, and mechanisms of MAC and review the effects of alpha-2 agonists,
      benzodiazepines, and propofol on MAC. DATABASES USED: PubMed, Google Scholar, CAB
      Abstracts. Search terms used: minimum alveolar concentration, MAC, dog, canine,
      inhaled anesthetic potency, isoflurane, sevoflurane, desflurane, enflurane, and
      halothane. CONCLUSIONS: Many drugs reduce the MAC of inhaled anesthetics in dogs,
      and allow for a clinically important decrease in inhalant anesthetic use. A
      decrease in MAC may decrease the adverse cardiovascular and pulmonary effects
      associated with the use of high concentrations of inhaled anesthetics.

PMID- 29331923
TI  - Cold-regulated protein (SlCOR413IM1) confers chilling stress tolerance in tomato
      plants.
AB  - Chilling stress severely affects the growth, development and productivity of
      crops. Chloroplast, a photosynthesis site, is extremely sensitive to chilling
      stress. In this study, the functions of a gene encoding a cold-regulated protein
      (SlCOR413IM1) under chilling stress were investigated using sense and antisense
      transgenic tomatoes. Under chilling stress, SlCOR413IM1 expression was rapidly
      induced and the sense lines exhibited better growth state of seedlings and grown
      tomato plants. Overexpression of SlCOR413IM1 alleviated chilling-induced damage
      to the chloroplast membrane and structure, whereas suppression of SlCOR413IM1
      aggravated the damage to chloroplast. Moreover, the net photosynthetic rate (Pn),
      maximum photochemical efficiency of photosystem II (PSII) (Fv/Fm), actual
      photochemical efficiency of PSII (PhiPSII) and the activities of glyceraldehyde-3
      phosphate dehydrogenase (GAPDH) and stromal fructose-1, 6-bisphosphatase
      (sFBPase) were higher in the sense lines than those in the antisense lines.
      Hence, the inhibition of photosynthetic capacity was less severe in the sense
      lines but more severe in the antisense lines compared with that in wild-type (WT)
      plants. Taken together, overexpression of SlCOR413IM1 enhanced the chilling
      stress tolerance, whereas suppression of this gene increased the chilling
      sensitivity of tomato plants.

PMID- 29331924
TI  - Gene expression patterns regulating the seed metabolism in relation to
      deterioration/ageing of primed mung bean (Vigna radiata L.) seeds.
AB  - We are proposing mechanisms to account for the loss of viability (seed
      deterioration/ageing) and enhancement in seed quality (post-storage priming
      treatment). In order to understand the regulatory mechanism of these traits, we
      conducted controlled deterioration (CD) test for up to 8 d using primed mung bean
      seeds and examined how CD effects the expression of many genes, regulating the
      seed metabolism in relation to CD and priming. Germination declined progressively
      with increased duration of CD, and the priming treatment completely/partially
      reversed the inhibition depending on the duration of CD. The loss of germination
      capacity by CD was accompanied by a reduction in total RNA content and RNA
      integrity, indicating that RNA quantity and quality impacts seed longevity.
      Expression analysis revealed that biosynthesis genes of GA, ethylene, ABA and ROS
      scavenging enzymes were differentially affected in response to duration of CD and
      priming, suggesting coordinately regulated mechanisms for controlling the
      germination capacity of seeds by modifying the permeability characteristics of
      biological membranes and activities of different enzymes. ABA genes were highly
      expressed when germination was delayed and inhibited by CD. Whereas, GA and
      ethylene genes were more highly expressed when germination was enhanced and
      permitted by priming under similar conditions. GSTI, a well characterized enzyme
      family involved in stress tolerance, was expressed in primed seeds over the
      period of CD, suggesting an additional protection against deterioration. The
      results are discussed in light of understanding the mechanisms underlying
      longevity/priming which are important issues economically and ecologically.

PMID- 29331925
TI  - Overexpression of Chrysanthemum lavandulifolium ClCBF1 in Chrysanthemum
      morifolium 'White Snow' improves the level of salinity and drought tolerance.
AB  - This paper reports the first study on plant CBF transcription factors (TF) in
      salt and drought stress responses in Chrysanthemum lavandulifolium. A CBF homolog
      gene, named as ClCBF1, from C. lavandulifolium was isolated using rapid
      amplification of cDNA ends (RACE). The deduced peptide is comprised of 210 amino
      acids (AA) containing an AP2 structural domain characteristic of the AP2 gene
      family. Quantitative real-time PCR revealed that ClCBF1 gene exhibit differential
      expression patterns across root, leaf and stem tissues, and it was strongly
      induced under salt and drought treatments of C. lavandulifolium. Overexpression
      of ClCBF1 in C. morifolium 'White Snow' resulted in stronger tolerance to salt
      and drought stresses. The ClCBF1 expression level, enzymatic activities of
      superoxide dismutase and peroxidase, and contents of proline and soluble proteins
      were enhanced in these transgenic lines, they were repressed in the antisense
      transgenic lines under the same stress conditions. Results indicate that ClCBF1
      represents a promising candidate gene in improving abiotic stress tolerance among
      ornamental plants.

PMID- 29331926
TI  - Two hump-shaped angular distributions of neutrons and soft X-rays in a small
      plasma focus device.
AB  - Angular distributions of soft X-rays (SXRs) and neutrons emitted by a small
      plasma focus device (PFD) were investigated simultaneously using TLD-100
      dosimeters and Geiger-Muller activation counters, respectively. The distributions
      represented two humps with a small dip at the angular position 0 degrees  and
      reduced from the angles of +/- 15 degrees  and +/- 30 degrees  for the neutrons
      and SXRs, respectively. The maximum yield of 2.98 * 108 neutrons per shot of the
      device was obtained at 13.5kV and 6.5mbar. A time of flight (TOF) of 75.2ns
      between the hard X-ray and the neutron peaks corresponds to neutrons with energy
      of 2.67MeV. A similar behavior was observed between the angular distributions of
      neutron and soft X-ray emissions.

PMID- 29331927
TI  - Honeycomb-like polysulphone/polyurethane nanofiber filter for the removal of
      organic/inorganic species from air streams.
AB  - Nanofiber nonwoven filters, especially those prepared by electrospinning, are of
      particular interest because of their high filtration efficiency. However,
      existing electrospun filters suffer from inherent limitations in that both
      strengths and filtration resistances of the filters leave much to be desired.
      Herein, we present a novel nonwoven filter that is composed of polysulphone and
      polyurethane nanofibers. By mimicking the honeycomb structure, a heterogeneous
      distribution of both fiber diameter and fiber density has been achieved. Compared
      with nanofiber nonwovens with plain architectures, the honeycomb-like nonwovens
      possess higher filtration efficiency (~99.939%), better mechanical strength
      (~105.24 N g-1) and improved quality factor (~0.04 Pa-1). The filtration
      efficiency against both inorganic and organic aerosols is guaranteed through the
      nanofiber surface geometry and the intrinsic charge-retention capacity of
      polysulphone. Since the production of this nanofiber filter does not need
      multistep procedures and can be easily scaled up on a needleless electrospinning
      device, we anticipate that the strategy of endowing nanofibers with honeycomb
      texture and charge-retention capacity may lead to the development of advanced
      fiber filters.

PMID- 29331928
TI  - Being in control? A thematic content analysis of 14 in-depth interviews with 2,4
      dinitrophenol users.
AB  - BACKGROUND: 2,4-Dinitrophenol (2,4-DNP) is a compound with multiple industrial
      purposes. Currently unlicensed for human consumption, it is used by the gym-going
      population for drastic, short-term body fat loss. Nonetheless, physiological
      mechanisms can lead to potentially fatal hyperthermia. Reported fatal incidents
      have caused concern and highlighted the need for intervention. Understanding
      decision-making leading to 2,4-DNP use alongside the perceived outgroup attitudes
      is vital to forming effective harm minimisation policies targeting current and
      potential users. First-hand accounts from this elusive population are scarce.
      METHODS: Fourteen novel and experienced users (13 male, 1 female) were recruited
      via "snowballing" techniques. Semi-structured interviews were conducted,
      comprising 28 questions. Thematic content analysis was conducted using 37 codes.
      RESULTS: Four characteristic themes emerged: 1. Users considered the Internet to
      be a crucial multifunctional resource directly impacting their 2,4-DNP use. 2.
      Users "respected" 2,4-DNP, proactively taking harm reduction measures. 3.
      Attitudinal polarisation towards 2,4-DNP within the gym-going community was
      consistent in all accounts. 4. Users perceived outgroup populations to have
      inherently negative attitudes towards their use. These themes fell under the all
      encompassing theme of "being in control". CONCLUSION: For the first time, this
      study offers a rich detail of attitudes toward 2,4-DNP use by giving a collective
      voice to users. The element of control over every aspect of the users' life
      appears to be a significant contributor to the successful risk-management of 2,4
      DNP use. In the absence of an established safe upper limit and effective
      regulatory control, education is critical to harm minimisation.

PMID- 29331929
TI  - Sex-related differential response to dexamethasone in endocrine and immune
      measures in depressed in-patients and healthy controls.
AB  - Although sex differences in major depression have been reported repeatedly, the
      underlying mechanisms are still disputed. The rapidly changing gonadal steroid
      concentrations of the postpartum period or during menopause have been shown to be
      associated with depressive symptoms and to modulate the hypothalamic-pituitary
      adrenal (HPA)-axis, which is implicated in depression. The sample comprised of
      128 depressed in-patients (36.7% women) and 166 healthy controls (30.0% women).
      Blood was collected at baseline (at 6pm) and then 3 h as well as 21 h after
      ingestion of 1.5 mg dexamethasone for measurement of cortisol, ACTH and blood
      count. To further assess the function of the HPA-axis the
      dexamethasone/corticotrophin releasing hormone (Dex-CRH) test was performed in a
      subsample of 115 patients and 116 controls the following day. A significant
      interaction effect between sex, disease and ACTH concentrations over time after
      dexamethasone stimulation was observed, with men showing increased ACTH
      concentrations at baseline and after 21 h, while there was no difference after 3
      h (p = .007). After separating for disease status this significant interaction
      effect was only observed in controls (p = .005). The cortisol response in the dex
      CRH test was enhanced in female compared to male controls (p = .002). Leucocytes
      showed a stronger increase upon dexamethasone administration only in female
      compared to male controls (p = .023). These findings suggest a higher
      glucocorticoid receptor sensitivity following in-vivo glucocorticoid stimulation
      in healthy women that was absent in depressed patients. The sex-related
      differences in HPA-axis regulation and immune system function may contribute to
      the vulnerability of female sex to the development of depression.

PMID- 29331930
TI  - Sleep quality, psychological symptoms, and psychotic-like experiences.
AB  - Poor sleep quality has been repeatedly linked to the entire psychosis continuum,
      including psychotic-like experiences (PLEs); however, sleep dysfunction is a
      component of several other psychopathologies that have also been linked to
      increased risk for PLEs, including depression, anxiety, and post-traumatic stress
      disorder (PTSD). It has yet to be examined if PLEs are a significant risk factor
      for poor sleep quality or if this sleep dysfunction is better accounted for by
      comorbid psychopathology. In 2687 undergraduates, PLEs were evaluated using the
      positive items of the Prodromal Questionnaire. Symptoms of anxiety, depression,
      and PTSD were also assessed, as was sleep quality. Mediation analysis using
      PROCESS was conducted to determine if poor sleep quality associated with PLEs was
      in fact more associated with symptoms of other psychopathologies. Symptoms of
      depression and PTSD mediated the relationship between PLEs and sleep quality,
      though anxiety symptoms did not. These findings suggest that treating symptoms of
      depression and PTSD may improve multiple domains of psychotic illness.

PMID- 29331931
TI  - Resting-state fMRI signals in offspring of parents with bipolar disorder at the
      high-risk and ultra-high-risk stages and their relations with cognitive function.
AB  - BACKGROUND: Bipolar disorder (BD) has been associated with dysfunctional resting
      state brain functioning. However, it is still not known whether the aberrant
      functioning occurs and predict cognitive functioning before illness onset. AIMS:
      We examined the resting-state regional and network dysfunctioning, and their
      correlates with neurocognitive performance, in the high-risk (HR) and ultra-high
      risk (UHR) stages of bipolar disorder. METHODS: Using amplitude of low-frequency
      fluctuations (ALFF), region homogeneity (ReHo) and hypothesis-driven region-of
      interest (ROI)-based connectivity, we examined resting-state fMRI data of 8- to
      25-year-old healthy offspring (HR, n = 28) and offspring with subthreshold
      syndromes (UHR, n = 22) of a BD parent, and age-matched healthy controls without
      any personal or family psychopathology (HC, n = 46). Participants' neurocognitive
      profiles were assessed using the MATRICS Consensus Cognitive Battery (MCCB).
      RESULTS: ALFF signals in the left putamen and right rolandic operculum were lower
      in the HR group compared to the HC group. In contrast, ALFF signals were
      increased in the UHR group in the right middle pars orbitalis of the inferior
      frontal gyrus, right calcarine sulcus and right cerebellum. Connectivities
      between the right amygdala and left inferior temporal gyrus, between the left
      hippocampus and inferior occipital gyrus, and between the left hippocampus and
      middle pars orbitalis gyrus were decreased in the HR group compared to the HC
      group. In UHR versus HC group, connectivity between the right amygdala and the
      left hippocampus and left insula was increased, and connectivity between the left
      hippocampus and the left insula and the cerebellum was also increased. Among
      cognitive measures, processing speed was positively correlated with ALFF signals
      in the left putamen in the HR offspring. In the UHR offspring, processing speed,
      attention, and verbal learning/memory were positively correlated with the
      functional connectivity between the left hippocampus and cerebellum. CONCLUSIONS:
      Offspring of parents with BD in the HR and UHR stages show largely non
      overlapping patterns of atypical resting-state signals and functional
      connectivity that predicted cognitive functioning, possibly reflecting inherited
      abnormalities and/or complimentary reactions.

PMID- 29331932
TI  - CNV biology in neurodevelopmental disorders.
AB  - Copy number variants (CNVs), characterized in recent years by cutting-edge
      technology, add complexity to our knowledge of the human genome. CNVs contribute
      not only to human diversity but also to different kinds of diseases including
      neurodevelopmental delay, autism spectrum disorder and neuropsychiatric diseases.
      Interestingly, many pathogenic CNVs are shared among these diseases. Studies
      suggest that pathophysiology of disease may not be simply attributed to a single
      driver gene within a CNV but also that multifactorial effects may be important.
      Gene expression and the resulting phenotypes may also be affected by epigenetic
      alteration and chromosomal structural changes. Combined with human genetics and
      systems biology, integrative research by multi-dimensional approaches using
      animal and cell models of CNVs are expected to further understanding of
      pathophysiological mechanisms of neurodevelopmental disorders and
      neuropsychiatric disorders.

PMID- 29331933
TI  - Combined effects of Ag and UiO-66 for removal of elemental mercury from flue gas.
AB  - The zirconium metal-organic framework material UiO-66 was doped with Ag
      nanoparticles and investigated for the removal of elemental mercury (Hg0) in flue
      gas. Physical and chemical characterization of the adsorbents showed that adding
      Ag did not change the crystal structure and morphology of the UiO-66. Ag doping
      can improve the redox activity of UiO-66, and the adsorbent exhibited high
      thermal stability and surface area. Hg0 removal experiments indicated that UiO-66
      exhibited the higher performance compared with P25 and activated carbon, and the
      addition of Ag exhibited a significant synergistic effect with the UiO-66, which
      had highest Hg0 adsorption capacity (3.7 mg/g) at 50  degrees C. Furthermore, the
      Hg0 removal mechanism was investigated, revealing that Hg0 is removed by the
      formation of an Ag amalgam and channel adsorption at low temperature, and through
      Ag-activated oxygen oxidation and channel capture at high temperature.

PMID- 29331934
TI  - Characterization and release profile of (Mn, Al)-bearing deposits in drinking
      water distribution systems.
AB  - Inorganic contaminants accumulation in drinking water distribution systems (DWDS)
      is a great threat to water quality and safety. This work assessed the main risk
      factors for different water pipes and discovered the release profile of
      accumulated materials in a full scale distribution system frequently suffered
      from water discoloration problem. Physicochemical characterization of pipe
      deposits were performed using X-ray fluorescence, scanning electron microscopy, X
      ray diffraction, X-ray photoelectron spectroscopy and Fourier transform infrared
      spectroscopy. The metal release profile was obtained through continuous
      monitoring of a full-scale DWDS area. The results showed that aluminum and
      manganese were the main metals of deposits in nonmetallic pipes, while iron was
      dominant in iron-based pipe corrosion scales. Manganese primarily existed as MnO2
      without well crystalline form. The relative abundance of Mn and Fe in deposits
      changed with their distance from the water treatment plant. Compared with iron in
      corrosion scales, Mn and Al were more labile to be released back into bulk water
      during unidirectional flushing process. A main finding of this work is the co
      release behavior of Mn and Al in particulate form and significant correlation
      exists between these two metals. Dual control of manganese and aluminum in
      treated water is proposed to be essential to cope with discoloration and trace
      metal contamination in DWDS.

PMID- 29331936
TI  - Influence of custom foot orthoses on venous status: A quasi-experimental study.
AB  - BACKGROUND: Customized foot orthoses (CFO) have been widely accepted to reduce
      the frequency of foot problems and postural disorders. The purpose of the
      research was to compare the influence of CFO utilization on the venous status
      among healthy females and males. METHODS: This was a quasi-experimental study
      (NCT03329430), which included 20 healthy subjects that completed all the stages
      of the process. The subjects showed an age mean of 20.00 +/- 1.62 years and were
      recruited in a foot and ankle specialist center. Self-reported data were medical
      records and venous function which were evaluated by plethysmography with or
      without utilization of CFO. RESULTS: A sample of 40 feet was studied, showing
      statistically significant differences between venous filling time (P < 0.001) and
      in the ejection fraction (P < 0.001) with CFO utilization versus without use of
      CFO. CONCLUSIONS: Healthy people who utilize CFO evidenced an increased venous
      return in the feet.

PMID- 29331935
TI  - Disruption of thyroid hormone sulfotransferase activity by brominated flame
      retardant chemicals in the human choriocarcinoma placenta cell line, BeWo.
AB  - Brominated flame retardants (BFRs) have been shown to disrupt thyroid hormone
      (TH) homeostasis through multiple mechanisms, including inhibition of enzymes
      that regulate intracellular levels of THs, such as sulfotransferases (SULTs). The
      placenta plays a critical role in helping to maintain TH levels during fetal
      development and expresses SULTs. This is concerning given that disruption of TH
      regulation within the placenta could potentially harm the developing fetus. In
      this study, we investigated the effects of two polybrominated diphenyl ethers
      (PBDEs), two hydroxylated PBDEs, and 2,4,6-tribromophenol (2,4,6-TBP) on TH SULT
      activity in a choriocarcinoma placenta cell line (BeWo). BeWo cells were exposed
      to BFR concentrations up to 1 MUM for 1-24 h to investigate changes in basal SULT
      activity and in mRNA expression of several TH regulating genes. 2,4,6-TBP was the
      most potent inhibitor of basal 3,3'-T2 SULT activity at all exposure durations,
      decreasing activity by as much as 86% after 24 h of exposure. BDE-99, 3-OH BDE
      47, and 6-OH BDE-47 also decreased 3,3'-T2 SULT activity by 23-42% at
      concentrations of 0.5 MUM and 1.0 MUM following 24 h exposures. BDE-47 had no
      effect on SULT activity, and there was no observed effect of any BFR exposure on
      expression of SULT1A1, or thyroid nuclear receptors alpha or beta. This research
      demonstrates that total TH SULT activity in placental cells are sensitive to BFR
      exposure; however, the mechanisms and consequences have yet to be fully
      elucidated.

PMID- 29331937
TI  - Quasi-static tensile properties of the Cranial Cruciate Ligament (CrCL) in adult
      cattle: towards the design of a prosthetic CrCL.
AB  - Mechanical properties of the Cranial Cruciate Ligament (CrCL) in adult cattle are
      not well documented and protocols used in the literature focus on testing a full
      femur-CrCL-tibia complex rather than an isolated CrCL. The aim of this study was
      to assess a wider range of tensile properties of the CrCL along its anatomic axis
      with experimental measurements of the global elongation, displacement and strain
      fields, in order to provide guidelines for the design of CrCL prosthetic
      surrogates. Fourteen bovine CrCL were harvested from seven mature cows (5.1 +/-
      1.3 years) weighing 631 +/- 90kg. The mean CrCL length was 41.4 +/- 1.5mm and its
      mean cross-section was 103.9 +/- 23.8mm2. Pre-conditioning was achieved with 30
      cycles of loading from 30 to 200N at a strain rate of 0.02s-1. Specimens were
      then loaded to failure at the same strain rate. The following results were
      obtained: the mean ultimate tensile load (UTL) 4372 +/- 1485N and the median
      [quartiles] maximal global elongation 19.3 [17.8; 21.4] %. At first physical
      signs of tearing, the mean load was 3315 +/- 1336N and mean elongation 13.5 +/-
      4.9%. The mean absorbed energy at failure was 5.23 +/- 2.08 MJ.mm-3 and the mean
      stiffness at various levels of elongation was: 220 +/- 195N.%-1 (5%), 285 +/-
      162N.%-1 (10%), 239 +/- 200N.%-1 (15%), 146 +/- 59N.%-1 (20%), 153 +/- 136N.%-1
      (25%). None of these properties were related to the bovine weight, age and side
      of the body (p > 0.05). An ideal prosthetic surrogate should then follow these
      sets of properties and the experimental data suggest that the in-vivo maximal
      elongation is below 13.5%.

PMID- 29331938
TI  - Generation of a human induced pluripotent stem cell line (CSC-40) from a
      Parkinson's disease patient with a PINK1 p.Q456X mutation.
AB  - Parkinson's disease (PD) is a neurodegenerative disease with unknown etiology.
      Here we show the generation of an induced pluripotent stem cell (iPSC) line,
      named CSC-40, from dermal fibroblasts obtained from a 59-year-old male patient
      with a homozygous p.Q456X mutation in the PTEN-induced putative kinase 1
      (PINK/PARK6) gene and a confirmed diagnosis of PD, which could be used to model
      familial PD. A non-integrating Sendai virus-based delivery of the reprogramming
      factors OCT3/4, SOX2, c-MYC and KLF4 was employed. The CSC-40 cell line showed
      normal karyotyping and fingerprinting following transduction as well as sustained
      expression of several pluripotency markers and the ability to differentiate into
      all three germ layers.

PMID- 29331939
TI  - Volumetric muscle loss injury repair using in situ fibrin gel cast seeded with
      muscle-derived stem cells (MDSCs).
AB  - Volumetric muscle defect, caused by trauma or combat injuries, is a major health
      concern leading to severe morbidity. It is characterized by partial or full
      thickness loss of muscle and its bio-scaffold, resulting in extensive fibrosis
      and scar formation. Therefore, the ideal therapeutic option is to use stem cells
      combined with bio-scaffolds to restore muscle. For this purpose, muscle-derived
      stem cells (MDSCs) are a great candidate due to their unique multi-lineage
      differentiation potential. In this study, we evaluated the regeneration potential
      of MDSCs for muscle loss repair using a novel in situ fibrin gel casting. Muscle
      defect was created by a partial thickness wedge resection in the tibialis
      anterior (TA) muscles of NSG mice which created an average of 25% mass loss. If
      untreated, this defect leads to severe muscle fibrosis. Next, MDSCs were
      delivered using a novel in situ fibrin gel casting method. Our results
      demonstrated MDSCs are able to engraft and form new myofibers in the defect when
      casted along with fibrin gel. LacZ labeled MDSCs were able to differentiate
      efficiently into new myofibers and significantly increase muscle mass. This was
      also accompanied by significant reduction of fibrotic tissue in the engrafted
      muscles. Furthermore, transplanted cells also contributed to new vessel formation
      and satellite cell seeding. These results confirmed the therapeutic potential of
      MDSCs and feasibility of direct in situ casting of fibrin/MDSC mixture to repair
      muscle mass defects.

PMID- 29331940
TI  - Screening and functional exploration of prothrombin Arg596 related mutations in
      Chinese venous thromboembolism patients.
AB  - AIMS: Dysfunctional prothrombin residue Arg596 associated mutation has been found
      to precipitate venous thromboembolism (VTE). In the current study we investigated
      the prevalence of Arg596 associated mutations in Chinese patients with VTE and
      explored the functional impact of Arg596Gln mutation on coagulation function in
      affected patients. METHODS: Prothrombin clotting activity was measured in 267
      unrelated patients with unprovoked VTE. Patients with moderately decreased
      activities underwent further analysis of the F2 gene. Prothrombin amidolytic
      activity and antigen levels were detected in mutation carriers. Specific family
      members were investigated about their VTE histories and clinical phenotypes. The
      thrombin generation test (TGT) was used to evaluate thrombin function and
      antithrombin resistance assay was applied to assess the extent of impaired
      antithrombin inhibition of mutation carriers. RESULTS: Two heterozygous mutation
      carriers of prothrombin Arg596Gln were identified, both of whom had moderately
      decreased clotting activities but normal amidolytic activities and antigen
      levels. Among the families of the two probands, nine out of 13 mutation carriers
      experienced episodes of VTE. TGTs showed that patients had elevated endogenous
      thrombin potential and prolonged start tail time. Thrombin generation could be
      inhibited in the presence of thrombomodulin. The thrombin Arg596Gln variant in
      patients' plasma presented strong resistance to antithrombin inhibition.
      CONCLUSION: Prothrombin Arg596Gln mutation is a risk factor for Chinese patients
      with VTE due to its moderately decreased clotting activity but strong resistance
      to antithrombin inhibition. Prothrombin clotting activity screening and its
      encoding gene sequencing should be considered in patients with VTE when other
      established risk factors are absent.

PMID- 29331941
TI  - Early changes in the pharmacokinetic profile of vedolizumab-treated patients with
      IBD may predict response after dose optimisation.

PMID- 29331942
TI  - Sucrase-isomaltase 15Phe IBS risk variant in relation to dietary carbohydrates
      and faecal microbiota composition.

PMID- 29331943
TI  - Modern management of perianal fistulas in Crohn's disease: future directions.
AB  - Perianal fistulae in patients with Crohn's disease (CD) can be associated with
      significant morbidity resulting in negative impact on quality of life. The last
      two decades have seen significant advancements in the management of perianal
      fistulas in CD, which has evolved into a multidisciplinary approach that includes
      gastroenterologists, colorectal surgeons, endoscopists and radiologists. Despite
      the introduction of new medical therapies such as antitumour necrosis factor and
      novel models of care delivery, the best fistula healing rates reported with
      combined medical and surgical approaches are approximately 50%. More recently,
      newer biologics, cell-based therapies as well as novel endoscopic and surgical
      techniques have been introduced raising new hopes that outcomes can be improved
      upon. In this review, we describe the modern management and the most recent
      advances in the management of complex perianal fistulising CD, which will likely
      impact clinical practice. We will explore optimal use of both older and newer
      biological agents, as well as new data on cell-based therapies. In addition, new
      techniques in endoscopic and surgical approaches will be discussed.

PMID- 29331945
TI  - Risk factors for gastric cancer: is it time to discard PPIs?

PMID- 29331944
TI  - Liver sampling: a vital window into HBV pathogenesis on the path to functional
      cure.
AB  - In order to optimally refine the multiple emerging drug targets for hepatitis B
      virus (HBV), it is vital to evaluate virological and immunological changes at the
      site of infection. Traditionally liver biopsy has been the mainstay of HBV
      disease assessment, but with the emergence of non-invasive markers of liver
      fibrosis, there has been a move away from tissue sampling. Here we argue that
      liver biopsy remains an important tool, not only for the clinical assessment of
      HBV but also for research progress and evaluation of novel agents. The importance
      of liver sampling has been underscored by recent findings of specialised subsets
      of tissue-resident immune subsets capable of efficient pathogen surveillance,
      compartmentalised in the liver and not sampled in the blood. Importantly, the
      assessment of virological parameters, such as cccDNA quantitation, also requires
      access to liver tissue. We discuss strategies to maximise information obtained
      from the site of infection and disease pathology. Fine needle aspirates of the
      liver may allow longitudinal sampling of the local virus/host landscape. The
      careful utilisation of liver tissue and aspirates in conjunction with blood will
      provide critical information in the assessment of new therapeutics for the
      functional cure of HBV.

PMID- 29331947
TI  - Response to: 'Prognosis of immune-tolerant phase chronic hepatitis B' by Chu and
      Liaw.

PMID- 29331948
TI  - LVIS Blue as a low porosity stent and coil adjuvant.
AB  - INTRODUCTION: The LVIS Blue is an FDA-approved stent with 28% metallic coverage
      that is indicated for use in conjunction with coil embolization for the treatment
      of intracranial aneurysms. Given a porosity similar to approved flow diverters
      and higher than currently available intracranial stents, we sought to evaluate
      the effectiveness of this device for the treatment of intracranial aneurysms.
      METHODS: We performed an observational single-center study to evaluate initial
      occlusion and occlusion at 6-month follow-up for patients treated with the LVIS
      Blue in conjunction with coil embolization at our institution using the modified
      Raymond-Roy classification (mRRC), where mRRC 1 indicates complete embolization,
      mRRC 2 persistent opacification of the aneurysm neck, mRRC 3a filling of the
      aneurysm dome within coil interstices, and mRRC 3b filling of the aneurysm dome.
      RESULTS: Sixteen aneurysms were treated with the LVIS Blue device in conjunction
      with coil embolization with 6-month angiographic follow-up. Aneurysms were
      treated throughout the intracranial circulation: five proximal internal carotid
      artery (ICA) (ophthalmic or communicating segments), two superior cerebellar
      artery, two ICA terminus, two anterior communicating artery, two distal middle
      cerebral artery, one posterior inferior cerebellar artery, and two basilar tip
      aneurysms. Post-procedurally, there was one mRRC 1 closure, five mRRC 2 closures,
      and 10 mRRC 3a or 3b occlusion. At follow-up, all the mRRC 1 and mRRC 3a
      closures, 85% of the mRRC 3b closures and 75% of the mRRC 2 closures were stable
      or improved to an mRRC 1 or 2 at follow-up. CONCLUSIONS: The LVIS Blue represents
      a safe option as a coil adjunct for endovascular embolization within both the
      proximal and distal anterior and posterior circulation.

PMID- 29331946
TI  - Management of patients on antithrombotic agents undergoing emergency and elective
      endoscopy: joint Asian Pacific Association of Gastroenterology (APAGE) and Asian
      Pacific Society for Digestive Endoscopy (APSDE) practice guidelines.
AB  - This Guideline is a joint official statement of the Asian Pacific Association of
      Gastroenterology (APAGE) and the Asian Pacific Society for Digestive Endoscopy
      (APSDE). It was developed in response to the increasing use of antithrombotic
      agents (antiplatelet agents and anticoagulants) in patients undergoing
      gastrointestinal (GI) endoscopy in Asia. After reviewing current practice
      guidelines in Europe and the USA, the joint committee identified unmet needs,
      noticed inconsistencies, raised doubts about certain recommendations and
      recognised significant discrepancies in clinical practice between different
      regions. We developed this joint official statement based on a systematic review
      of the literature, critical appraisal of existing guidelines and expert consensus
      using a two-stage modified Delphi process. This joint APAGE-APSDE Practice
      Guideline is intended to be an educational tool that assists clinicians in
      improving care for patients on antithrombotics who require emergency or elective
      GI endoscopy in the Asian Pacific region.

PMID- 29331950
TI  - Construction of an evaluation index system for determining the academic impact of
      military medical scholars.
AB  - INTRODUCTION: Academic papers are an essential manner for describing new ideas
      and consolidating existing concepts in the field of military medicine. The
      academic impact of military medical publications reflects the extent and depth of
      recognition, acceptance and utilisation of the concepts transmitted in these
      publications. The aim of this research was to construct an evaluation index
      system suitable for evaluating the academic influence of scholars in the field of
      military medicine. METHODS: Using the Delphi consensus methodology, 30 experts
      from the field of military medicine, military medical information and library and
      information science were asked during three rounds of questioning to score the
      feasibility and importance of indicators that could be used to determine academic
      impact. An analytic hierarchy process method was used to calculate the relative
      weighting of each indicator in determining the final level of academic impact.
      RESULTS: Eight evaluation indicators were agreed on to potentially determine
      academic impact. These comprised: 'Web of Science documents', 'Citation impact',
      'h-index', 'Percentage of international collaborations', 'Percentage of the top
      10% of the cited frequency', 'Category normalised citation impact', 'Percentage
      of documents cited' and 'The number of F1000 Recommended papers'. CONCLUSIONS:
      The evaluation index system determined from this study combines the advantages of
      both qualitative and quantitative recognised evaluation indicators, which are
      subsequently weighted according to their importance in the field of military
      medicine. It is hoped that this framework will provide a manner in the future for
      comparing the potential academic impact of military medical scholars.

PMID- 29331949
TI  - Bibliometric analysis of military trauma publications: 2000-2016.
AB  - INTRODUCTION: Bibliometric tools can be used to identify the authors, topics and
      research institutions that have made the greatest impact in a field of medicine.
      The aim of this research was to analyse military trauma publications over the
      last 16 years of armed conflict in order to highlight the most important lessons
      that have translated into civilian practice and military doctrine as well as
      identify emerging areas of importance. METHODS: A systematic search of research
      published between January 2000 and December 2016 was conducted using the Thompson
      Reuters Web of Science database. Both primary evidence and review publications
      were included. Results were categorised according to relevance and topic and the
      30 most cited publications were reviewed in full. The h-index, impact factors,
      citation counts and citation analysis were used to evaluate results. RESULTS: A
      plateau in the number of annual publications on military trauma was found, as was
      a shift away from publications on wound and mortality epidemiology to
      publications on traumatic brain injury (TBI), neurosurgery or blast injury to the
      head. Extensive collaboration networks exist between highly contributing authors
      and institutions, but less collaboration between authors from different
      countries. The USA produced the majority of recent publications, followed by the
      UK, Germany and Israel. CONCLUSIONS: In recent years, the number of publications
      on TBI, neurosurgery or blast injury to the head has increased. It is likely that
      the lessons of recent conflicts will continue to influence civilian medical
      practice, particularly regarding the long-term effects of blast-related TBI.

PMID- 29331951
TI  - SITA-Standard perimetry has better performance than FDT2 matrix perimetry for
      detecting glaucomatous progression.
AB  - PURPOSE: The Humphrey Matrix (FDT2) may be more sensitive in detecting
      glaucomatous visual field loss than SITA standard automated perimetry (SAP)
      performed on the Humphrey Field Analyzer (HFA). Therefore, FDT may be a good
      candidate to determine disease progression in patients with glaucoma. Our aim was
      to test the hypothesis that automated perimetry using the FDT2 would be equal to,
      or more effective than, HFA SITA-Standard, in identifying glaucomatous
      progression. METHODS: One hundred and twenty patients with glaucoma were tested
      twice at baseline and every 6 months for 4 years with HFA SITA-Standard and FDT2.
      FDT2 values were standardised to HFA SAP values. We used pointwise linear
      regression (PLR) over the full data series to identify glaucomatous progression
      and generated an array of results using three different criteria: (1) three or
      more clustered test locations progressing, (2) three or more non-clustered test
      locations progressing and (3) total number of progressing test locations. We
      compared HFA SAP and FDT2 for the number of locations signalled by the PLR
      detection algorithm. RESULTS: Regardless of the criteria, HFA SAP with SITA
      Standard testing detected visual field progression at a higher rate than the FDT2
      overall (P<0.001). CONCLUSION: HFA SAP identifies glaucomatous visual field
      progression at a rate at least as high if not higher than FDT2.

PMID- 29331952
TI  - Inter-relationship between ocular perfusion pressure, blood pressure, intraocular
      pressure profiles and primary open-angle glaucoma: the Singapore Epidemiology of
      Eye Diseases study.
AB  - OBJECTIVE: To elucidate the inter-relationship between ocular perfusion pressure
      (OPP), blood pressure (BP), intraocular pressure (IOP) profiles and primary open
      angle glaucoma (POAG) in a multiethnic Asian population. METHODS: Participants
      were recruited from the Singapore Epidemiology of Eye Diseases Study and
      underwent standardised ocular and systemic examinations. POAG was defined
      according to the International Society for Geographical and Epidemiological
      Ophthalmology criteria. Logistic regression analyses with generalised estimating
      equation models were performed and used to account for correlation between eyes.
      RESULTS: A total of 9877 participants (19 587 eyes), including 213 POAG cases
      (293 eyes) were included. Eyes with lowest quartile levels of systolic OPP (SOPP
      <110 mm Hg) were 1.85 times (95% CI 1.16 to 2.95) likely to have POAG, compared
      with eyes with mid-range SOPP levels (123-137 mm Hg; third quartile), after
      adjusting for relevant covariates and IOP. Consistently, we found that lowest
      quartile of systolic BP (SBP <124 mm Hg) was 1.69 times (95% CI 1.08 to 2.66)
      likely to have POAG, compared with mid-range SBP levels (138-153 mm Hg; third
      quartile). Furthermore, the effect of lower SBP on POAG was more pronounced in
      eyes with IOP >=21 mm Hg (OR 3.90; 95% CI 1.24 to 12.30). Both the mean and
      diastolic profiles of OPP and BP were not significantly associated with POAG,
      after adjusting for relevant covariates and IOP. CONCLUSIONS: In this population
      based sample of nearly 10 000 Asian individuals, we showed that low SOPP was
      associated with POAG. This association was potentially in part secondary to low
      SBP and high IOP. Our findings provide further clarity on the roles of OPP
      surrogates and BP profiles in POAG.

PMID- 29331953
TI  - Efficacy, tolerability and acceptability of oxycodone for cancer-related pain in
      adults: an updated Cochrane systematic review.
AB  - OBJECTIVES: To assess the efficacy, tolerability and acceptability of oxycodone
      for cancer pain in adults METHODS: We searched CENTRAL, MEDLINE, MEDLINE In
      Process, Embase, SCI, Conference Proceedings Citation Index-Science, BIOSIS,
      PsycINFO and four trials registries to November 2016. RESULTS: We included 23
      randomised controlled trials with 2144 patients analysed for efficacy and 2363
      for safety. Meta-analyses showed no significant differences between controlled
      release (CR) and immediate-release oxycodone in pain intensity or adverse events
      but did show significantly better pain relief after treatment with CR morphine
      compared with CR oxycodone. However, sensitivity analysis did not corroborate
      this result. Meta-analyses of the adverse events showed a significantly lower
      risk of hallucinations after treatment with CR oxycodone compared with CR
      morphine, but no other differences. The remaining studies either compared
      oxycodone in various formulations or compared oxycodone to different alternative
      opioids. None found any clear superiority or inferiority of oxycodone in pain
      relief or adverse events. The quality of this evidence base was limited by the
      high/unclear risk of bias of the studies and the low event rates for many
      outcomes. CONCLUSIONS: Oxycodone offers similar levels of pain relief and adverse
      events to other strong opioids. However, hallucinations occurred less with CR
      oxycodone than with CR morphine, but the quality of this evidence was very low,
      so this finding should be treated with utmost caution. Our conclusions are
      consistent with other reviews and suggest that oxycodone can be used first line
      as an alternative to morphine. However, because it is cheaper, morphine generally
      remains the first-line opioid of choice.

PMID- 29331954
TI  - Dynamics of dignity and safety: a discussion.

PMID- 29331955
TI  - Low-value care: an intractable global problem with no quick fix.

PMID- 29331957
TI  - Mitral Valve Anatomic Predictors of Hemodynamic Success With Transcatheter Mitral
      Valve Repair.
AB  - BACKGROUND: Mitral regurgitation is a heterogeneous disease. Determining which
      patients derive optimal outcomes from transcatheter edge-to-edge mitral valve
      repair (TMVR) remains challenging. We sought to determine whether baseline mitral
      valve anatomic characteristics are predictive of left atrial pressure (LAP)
      changes during TMVR with MitraClip. METHODS AND RESULTS: Consecutive patients
      with severe mitral regurgitation undergoing TMVR (n=112) underwent continuous
      intraprocedural LAP monitoring and retrospective echocardiographic analysis for
      specific mitral anatomic characteristics. Procedural success (optimal LAP
      reduction) was defined as >=40% reduction in left atrial V-wave pressure compared
      with baseline. Echocardiographic predictors of optimal LAP reduction and
      increased postprocedure mean diastolic gradient were evaluated. Mean age was 79+/
      14 years, and 36 patients (32%) were women. Primary, mixed, and secondary mitral
      regurgitation were present in 78 patients (70%), 22 patients (20%), and 12
      patients (10%), respectively. Baseline mean LAP and V-wave were 22+/-6 and 38+/
      13 mm Hg; after TMVR, these decreased to 19+/-5 and 27+/-10 mm Hg, respectively
      (P<0.0001 for both). Independent predictors of optimal LAP reduction were the
      presence of a flail scallop, mitral regurgitation localized to a single scallop,
      and high-quality 3-dimensional echocardiographic imaging. Independent predictors
      of elevated postprocedure mean diastolic gradient were elevated preprocedure mean
      diastolic gradient, mitral annular calcification, and implantation of multiple
      clips. CONCLUSIONS: Mitral valve pathoanatomic features, including a flail
      leaflet and single jet, are predictive of optimal LAP reduction with TMVR. High
      quality 3-dimensional imaging may help select patients with the highest
      likelihood of optimal hemodynamic results with TMVR. These data expand current
      knowledge about patient selection for TMVR and deserve further study in larger
      cohorts.

PMID- 29331956
TI  - Adenosine Production by Biomaterial-Supported Mesenchymal Stromal Cells Reduces
      the Innate Inflammatory Response in Myocardial Ischemia/Reperfusion Injury.
AB  - BACKGROUND: During myocardial ischemia/reperfusion (MI/R) injury, there is
      extensive release of immunogenic metabolites that activate cells of the innate
      immune system. These include ATP and AMP, which upregulate chemotaxis, migration,
      and effector function of early infiltrating inflammatory cells. These cells
      subsequently drive further tissue devitalization. Mesenchymal stromal cells
      (MSCs) are a potential treatment modality for MI/R because of their powerful anti
      inflammatory capabilities; however, the manner in which they regulate the acute
      inflammatory milieu requires further elucidation. CD73, an ecto-5'-nucleotidase,
      may be critical in regulating inflammation by converting pro-inflammatory AMP to
      anti-inflammatory adenosine. We hypothesized that MSC-mediated conversion of AMP
      into adenosine reduces inflammation in early MI/R, favoring a micro-environment
      that attenuates excessive innate immune cell activation and facilitates earlier
      cardiac recovery. METHODS AND RESULTS: Adult rats were subjected to 30 minutes of
      MI/R injury. MSCs were encapsulated within a hydrogel vehicle and implanted onto
      the myocardium. A subset of MSCs were pretreated with the CD73 inhibitor,
      alpha,beta-methylene adenosine diphosphate, before implantation. Using liquid
      chromatography/mass spectrometry, we found that MSCs increase myocardial
      adenosine availability following injury via CD73 activity. MSCs also reduce
      innate immune cell infiltration as measured by flow cytometry, and hydrogen
      peroxide formation as measured by Amplex Red assay. These effects were dependent
      on MSC-mediated CD73 activity. Finally, through echocardiography we found that
      CD73 activity on MSCs was critical to optimal protection of cardiac function
      following MI/R injury. CONCLUSIONS: MSC-mediated conversion of AMP to adenosine
      by CD73 exerts a powerful anti-inflammatory effect critical for cardiac recovery
      following MI/R injury.

PMID- 29331958
TI  - Platelet Secretion Defects and Acquired von Willebrand Syndrome in Patients With
      Ventricular Assist Devices.
AB  - BACKGROUND: The number of implanted ventricular assist devices (VADs) has
      increased significantly recently. Bleeding, the most frequent complication,
      cannot be solely attributed to anticoagulation therapy. Acquired von Willebrand
      syndrome (AVWS) caused by increased shear stress is frequent in VAD patients and
      can increase the bleeding risk. The HeartMate III (HM III) is a novel left VAD
      featuring potential improvements over the HeartMate II. METHODS AND RESULTS: In
      this study, we investigated the prevalence and onset of AVWS in 198 VAD patients.
      To our knowledge, this is the largest cohort of VAD patients whose longitudinal
      data on AVWS have been collected. We also analyzed whether AVWS is less severe in
      HM III patients than in HeartMate II patients. Because platelet dysfunction can
      raise the bleeding risk, we investigated platelet function in a subset of
      patients. In total, 198 VAD patients and 60 patients with heart transplants as
      controls were included in this study. The ratio of von Willebrand factor collagen
      binding capacity to von Willebrand factor:antigen, multimer analyses, and
      platelet function (especially secretion of alpha- and delta-granules) were
      investigated. All 198 VAD patients developed AVWS. As soon as the VAD was
      explanted, the AVWS disappeared within hours. AVWS was less severe in the HM III
      patients than in the HeartMate II patients. The HM III patients had fewer
      bleeding symptoms. In addition, VAD patients exhibited a platelet alpha- and
      delta-granule secretion defect. CONCLUSIONS: AVWS develops in VAD patients and
      may increase the bleeding risk. The HM III device causes less severe AVWS.
      Platelet secretion defects should be investigated in VAD patients because they
      also raise the bleeding risk. CLINICAL TRIAL REGISTRATION:
      https://www.drks.de/drks_web. Unique identifier: DRKS00000649.

PMID- 29331959
TI  - Probenecid Improves Cardiac Function in Patients With Heart Failure With Reduced
      Ejection Fraction In Vivo and Cardiomyocyte Calcium Sensitivity In Vitro.
AB  - BACKGROUND: Transient receptor potential vanilloid 2 is a calcium channel
      activated by probenecid. Probenecid is a Food and Drug Administration-approved
      uricosuric drug that has recently been shown to induce positive lusitropic and
      inotropic effects in animal models through cardiomyocyte transient receptor
      potential vanilloid 2 activation. The aim of this study was to test the
      hypothesis that oral probenecid can improve cardiac function and symptomatology
      in patients with heart failure with reduced ejection fraction and to further
      elucidate its calcium-dependent effects on myocyte contractility. METHODS AND
      RESULTS: The clinical trial recruited stable outpatients with heart failure with
      reduced ejection fraction randomized in a single-center, double-blind, crossover
      design. Clinical data were collected including a dyspnea assessment, physical
      examination, ECG, echocardiogram to assess systolic and diastolic function, a 6
      minute walk test, and laboratory studies. In vitro force generation studies were
      performed on cardiomyocytes isolated from murine tissue exposed to probenecid or
      control treatments. The clinical trial recruited 20 subjects (mean age 57 years,
      mean baseline fractional shortening of 13.6+/-1.0%). Probenecid therapy increased
      fractional shortening by 2.1+/-1.0% compared with placebo -1.7+/-1.0% (P=0.007).
      Additionally, probenecid improved diastolic function compared with placebo by
      decreasing the E/E' by -2.95+/-1.21 versus 1.32+/-1.21 in comparison to placebo
      (P=0.03). In vitro probenecid increased myofilament force generation (92.36
      versus 80.82 mN/mm2, P<0.05) and calcium sensitivity (pCa 5.67 versus 5.60,
      P<0.01) compared with control. CONCLUSIONS: Probenecid improves cardiac function
      with minimal effects on symptomatology and no significant adverse effects after 1
      week in patients with heart failure with reduced ejection fraction and increases
      force development and calcium sensitivity at the cardiomyocyte level. CLINICAL
      TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier:
      NCT01814319.

PMID- 29331960
TI  - Pregnancy Loss and Carotid Intima-Media Thickness in Mexican Women.
AB  - BACKGROUND: Cardiovascular disease in women often develops without conventional
      risk factors. Prenatal loss is a common pregnancy outcome that may result in
      physiological changes can increase the potential future risk of cardiovascular
      disease. Insufficient information exists regarding the impact of pregnancy loss
      on early markers of cardiovascular disease risk. METHODS AND RESULTS: Cross
      sectional analysis of 1767 disease-free women from the MTC (Mexican Teachers'
      Cohort) who had been pregnant was used to evaluate the relationship between
      pregnancy loss and carotid intima-media thickness (IMT). Participants responded
      to a questionnaire regarding their reproductive history, risk factors, and
      medical conditions. We defined pregnancy loss as history of miscarriage and/or
      stillbirth. Trained neurologists measured IMT using ultrasound. We log
      transformed IMT and defined subclinical carotid atherosclerosis (SCA) as IMT
      >=0.8 mm and/or plaque. We used multivariable linear and logistic regression
      models to assess the relation of pregnancy loss, IMT, and SCA. The mean age of
      participants was 49.8+/-5.1 years. The prevalence of pregnancy loss was 22%, and
      we observed SCA in 23% of participants. Comparing participants who reported a
      pregnancy loss and those who did not, the multivariable-adjusted odds ratio for
      SCA was 1.52 (95% confidence interval, 1.12-2.06). Women who experienced a
      stillbirth had 2.32 higher odds (95% confidence interval, 1.03-5.21) of SCA than
      those who did not. Mean IMT appeared to be higher in women who reported a
      pregnancy loss relative to those who did not; nevertheless, this was not
      statistically significant. CONCLUSIONS: Pregnancy loss could be linked to
      cardiovascular disease later in life. The key findings of our study await
      confirmation and further investigation of the potential underlying mechanisms for
      this association is required.

PMID- 29331961
TI  - Combining Intravenous Thrombolysis and Antithrombotic Agents in Stroke: An
      Update.

PMID- 29331963
TI  - Response to: 'Standard dose of ustekinumab for childhood-onset deficiency of
      interleukin-36 receptor antagonist' by Cherqaoui et al.

PMID- 29331962
TI  - Splicing variant of WDFY4 augments MDA5 signalling and the risk of clinically
      amyopathic dermatomyositis.
AB  - OBJECTIVES: Idiopathic inflammatory myopathies (IIMs) are a heterogeneous group
      of rare autoimmune diseases in which both genetic and environmental factors play
      important roles. To identify genetic factors of IIM including polymyositis,
      dermatomyositis (DM) and clinically amyopathic DM (CADM), we performed the first
      genome-wide association study for IIM in an Asian population. METHODS: We
      genotyped and tested 496 819 single nucleotide polymorphism for association using
      576 patients with IIM and 6270 control subjects. We also examined the causal
      mechanism of disease-associated variants by in silico analyses using publicly
      available data sets as well as by in in vitro analyses using reporter assays and
      apoptosis assays. RESULTS: We identified a variant in WDFY4 that was
      significantly associated with CADM (rs7919656; OR=3.87; P=1.5*10-8). This variant
      had a cis-splicing quantitative trait locus (QTL) effect for a truncated
      WDFY4isoform (tr-WDFY4), with higher expression in the risk allele.
      Transexpression QTL analysis of this variant showed a positive correlation with
      the expression of NF-kappaB associated genes. Furthermore, we demonstrated that
      both WDFY4 and tr-WDFY4 interacted with pattern recognition receptors such as
      TLR3, TLR4, TLR9 and MDA5 and augmented the NF-kappaB activation by these
      receptors. WDFY4 isoforms also enhanced MDA5-induced apoptosis to a greater
      extent in the tr-WDFY4-transfected cells. CONCLUSIONS: As CADM is characterised
      by the appearance of anti-MDA5 autoantibodies and severe lung inflammation, the
      WDFY4 variant may play a critical role in the pathogenesis of CADM.

PMID- 29331964
TI  - What are the characteristics of vitamin D metabolism in opioid dependence? An
      exploratory longitudinal study in Australian primary care.
AB  - OBJECTIVE: Compare vitamin D levels in opioid dependence and control population
      and adjust for relevant confounding effects. Nuclear hormone receptors (including
      the vitamin D receptor) have been shown to be key transducers and regulators of
      intracellular metabolism and comprise an important site of pathophysiological
      immune and metabolic dysregulation potentially contributing towards pro-ageing
      changes observed in opioid-dependent patients (ODPs). DESIGN: Longitudinal
      prospective comparing ODPs with general medical controls (GMCs). SETTING: Primary
      care. PARTICIPANTS: Prospective review comparing 1168 ODP (72.5% men) and 415 GMC
      (51.6% men, p<0.0001). Mean ages were 33.92+/-0.31 (mean+/-SEM) and 41.22+/-1.32
      years, respectively (p<0.0001). Opioid use in the ODP has been previously
      reported and shown to be typical. INTERVENTIONS: Nil. Observational study only.
      PRIMARY AND SECONDARY OUTCOMES: Serum vitamin D levels and relevant biochemical
      parameters. RESULTS: Vitamin D levels were higher in the ODP (70.35+/-1.16 and
      57.06+/-1.81 nmol/L, p<0.0001). The difference in ages between the two groups was
      handled in an age-matched case-control subanalysis and also by multiple
      regression. Sexes were analysed separately. The age:status (or age:time:status)
      was significant in case-control, cross-sectional and longitudinal analyses in
      both sexes (p<0.05). Modelled vitamin D was 62.71 vs 57.81 nmol/L in the two
      groups. Time-dependent mixed-effects models quadratic in age outperformed linear
      only models (p=0.0377). ODP vitamin D was shown to vary with age and to correlate
      with alanine aminotransferase establishing it as a biomarker of age in this
      group. Hepatitis C seronegativity was significant in regression models (from
      p=0.0015). CONCLUSION: Vitamin D was higher in ODP in both sexes in bivariate,
      cross-sectional, case-control and longitudinal analyses and was robust to the
      inclusion of metabolic and immune biomarkers. That Hepatitis C seronegativity was
      significant suggests opioid dependence has an effect beyond simply that of its
      associated hepatitides. This finding may relate to the accelerated ageing process
      previously described in opioid dependence.

PMID- 29331965
TI  - Right Iliac Fossa Pain Treatment (RIFT) Study: protocol for an international,
      multicentre, prospective observational study.
AB  - INTRODUCTION: Patients presenting with right iliac fossa (RIF) pain are a common
      challenge for acute general surgical services. Given the range of potential
      pathologies, RIF pain creates diagnostic uncertainty and there is subsequent
      variation in investigation and management. Appendicitis is a diagnosis which must
      be considered in all patients with RIF pain; however, over a fifth of patients
      undergoing appendicectomy, in the UK, have been proven to have a histologically
      normal appendix (negative appendicectomy). The primary aim of this study is to
      determine the contemporary negative appendicectomy rate. The study's secondary
      aims are to determine the rate of laparoscopy for appendicitis and to validate
      the Appendicitis Inflammatory Response (AIR) and Alvarado prediction scores.
      METHODS AND ANALYSIS: This multicentre, international prospective observational
      study will include all patients referred to surgical specialists with either RIF
      pain or suspected appendicitis. Consecutive patients presenting within 2-week
      long data collection periods will be included. Centres will be invited to
      participate in up to four data collection periods between February and August
      2017. Data will be captured using a secure online data management system. A
      centre survey will profile local policy and service delivery for management of
      RIF pain. ETHICS AND DISSEMINATION: Research ethics are not required for this
      study in the UK, as determined using the National Research Ethics Service
      decision tool. This study will be registered as a clinical audit in participating
      UK centres. National leads in countries outside the UK will oversee appropriate
      registration and study approval, which may include completing full ethical
      review. The study will be disseminated by trainee-led research collaboratives and
      through social media. Peer-reviewed publications will be published under
      corporate authorship including 'RIFT Study Group' and 'West Midlands Research
      Collaborative'.

PMID- 29331966
TI  - Effectiveness and safety of oral sedation in adult patients undergoing dental
      procedures: protocol for a systematic review.
AB  - INTRODUCTION: The management of anxious patients undergoing dental procedures is
      still a challenge in clinical practice. Despite a wide variety of drugs for oral
      sedation in adult patients, there are relatively few systematic reviews that
      compare the effectiveness and safety of different drugs administered via this
      route. Thus, this study will evaluate the effectiveness and safety of oral
      sedation with benzodiazepines and other agents to patients undergoing dental
      surgical procedures. METHOD/DESIGN: We will conduct a systematic review and, if
      appropriate, a meta-analysis of randomised controlled clinical trials that will
      evaluate the use of conscious sedation administered orally to adult patients
      undergoing oral surgery. The search will be conducted using electronic databases,
      such as the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE
      (via Ovid), EMBASE (via Ovid), CINAHL (via Ovid), Lilacs (SciELO) and Capes
      database, without restriction of languages or date of publication. Primary
      outcomes include anxiety, sedation, treatment satisfaction, pain and adverse
      effects. Secondary outcomes include vital parameters (heart rate, respiratory
      rate and blood pressure) and patient cooperation during intervention. A team of
      reviewers will independently assess each citation for eligibility and in
      duplicates. For eligible studies, the same reviewers will perform data
      extraction, risk of bias assessment and determination of the overall quality of
      evidence using the Grading of Recommendations Assessment, Development and
      Evaluation classification system. ETHICS AND DISSEMINATION: The evidence gathered
      from this study should provide dental surgeons with knowledge on the
      effectiveness and safety of oral sedation in adults requiring dental surgical
      procedures. This in turn should contribute towards the decision-making process in
      dental practice, minimising the risks of anxiety and ineffective pain control in
      clinical procedures, as well as possible side effects. Ethics approval is not
      required in protocols for systematic reviews. The systematic review will be
      published in a peer-reviewed journal and presented at conferences. PROSPERO
      REGISTRATION NUMBER: CRD42017057142.

PMID- 29331967
TI  - Understanding frailty: a qualitative study of European healthcare policy-makers'
      approaches to frailty screening and management.
AB  - OBJECTIVE: To elicit European healthcare policy-makers' views, understanding and
      attitudes about the implementation of frailty screening and management strategies
      and responses to stakeholders' views. DESIGN: Thematic analysis of semistructured
      qualitative interviews. SETTING: European healthcare policy departments.
      PARTICIPANTS: Seven European healthcare policy-makers representing the European
      Union (n=2), UK (n=2), Italy (n=1), Spain (n=1) and Poland (n=1). Participants
      were sourced through professional networks and the European Commission
      Authentication Service website and were required to be in an active healthcare
      policy or decision-making role. RESULTS: Seven themes were identified. Our
      findings reveal a 'knowledge gap', around frailty and awareness of the
      malleability of frailty, which has resulted in restricted ownership of frailty by
      specialists. Policy-makers emphasised the need to recognise frailty as a clinical
      syndrome but stressed that it should be managed via an integrated and
      interdisciplinary response to chronicity and ageing. That is, through social co
      production. This would require a culture shift in care with redeployment of
      existing resources to deliver frailty management and intervention services.
      Policy-makers proposed barriers to a culture shift, indicating a need to be
      innovative with solutions to empower older adults to optimise their health and
      well-being, while still fully engaging in the social environment. The cultural
      acceptance of an integrated care system theme described the complexities of
      institutional change management, as well as cultural issues relating to working
      democratically, while in signposting adult care, the need for a personal
      navigator to help older adults to access appropriate services was proposed.
      Policy-makers also believed that screening for frailty could be an effective tool
      for frailty management. CONCLUSIONS: There is potential for frailty to be managed
      in a more integrated and person-centred manner, overcoming the challenges
      associated with niche ownership within the healthcare system. There is also a
      need to raise its profile and develop a common understanding of its malleability
      among stakeholders, as well as consistency in how and when it is measured.

PMID- 29331969
TI  - Temporal trends in antithrombotic treatment of real-world UK patients with newly
      diagnosed atrial fibrillation: findings from the GARFIELD-AF registry.
AB  - OBJECTIVE: To investigate evolving patterns in antithrombotic treatment in UK
      patients with newly diagnosed non-valvular atrial fibrillation (AF). DESIGN:
      Prospective, multicentre, international registry. SETTING: 186 primary care
      practices in the UK. PARTICIPANTS: 3482 participants prospectively enrolled in
      four sequential cohorts (cohort 2 (C2) n=830, diagnosed September 2011 to April
      2013; cohort 3 (C3) n=902, diagnosed April 2013 to June 2014; cohort 4 (C4)
      n=850, diagnosed July 2014 to June 2015; cohort 5 (C5) n=900, diagnosed June 2015
      to July 2016). Participants had newly diagnosed non-valvular AF and at least one
      risk factor for stroke, were aged >=18, and provided informed consent. MAIN
      OUTCOME MEASURES: Antithrombotic treatment initiated at diagnosis, overall and
      according to stroke and bleeding risks. Stroke risk was retrospectively
      calculated using CHA2DS2-VASc (cardiac failure, hypertension, age >=75 (doubled),
      diabetes, stroke (doubled)-vascular disease, age 65-74 and sex category (female))
      and bleeding risk using HAS-BLED (hypertension, abnormal renal/liver function (1
      point each), stroke, bleeding history or predisposition, elderly (>65),
      drugs/alcohol concomitantly (1 point each)). RESULTS: 42.7% were women and the
      mean age was 74.5 years. The median CHA2DS2-VASc score was 3 in all cohorts and
      the median HAS-BLED score was 2 in all cohorts. There was a statistically
      significant increase in the use of anticoagulant therapy from C2 to C5 (C2 54.7%,
      C3 60.3%, C4 73.1%, C5 73.9%; P value for trend <0.0001). The increase in the use
      of anticoagulant was mainly in patients with CHA2DS2-VASc >=2. The use of vitamin
      K antagonists (VKAs)+/-antiplatelet (AP) drugs decreased from C2 to C5 (C2 53.3%,
      C3 52.1%, C4 50.3%, C5 30.6%), while the use of non-vitamin K antagonist oral
      anticoagulants (NOACs)+/-AP increased (C2 1.3%, C3 8.0%, C4 22.7%, C5 43.3%). The
      use of AP only decreased (C2 36.4%, C3 25.5%, C4 11.9%, C5 10.5%), as did the
      combination therapy of VKA+AP (C2 13.6%, C3 11.0%, C4 9.6%, C5 5.8%). CONCLUSION:
      There has been a progressive increase in the proportion of patients newly
      diagnosed with AF receiving guideline-recommended therapy in the UK, potentially
      driven by the availability of NOACs. TRIAL REGISTRATION NUMBER: NCT01090362; Pre
      results.

PMID- 29331968
TI  - Association between health service utilisation of internal migrant children and
      parents' acculturation in Guangdong, China: a cross-sectional study.
AB  - OBJECTIVES: To assess the health service utilisation of internal migrant children
      in Guangdong, China, and to explore the association between children's health
      service utilisation and their parents' acculturation. DESIGN: Cross-sectional
      survey between April and May 2016. SETTING: Six society-run schools of Tianhe and
      Baiyun districts in Guangzhou City of China. PARTICIPANTS: We recruited all
      students at grade 7 or 8 and one of their parents who resided in Guangzhou over 6
      months without permanent registered residence (hukou) in Guangzhou (1161 pairs
      completed this survey). 258 children were ill within the past 2 weeks or during
      the last year. MAIN OUTCOME MEASURES: The main outcome was self-reported health
      service utilisation. Logistic regression analysis was conducted to explore the
      association between children's unmet needs for outpatient or inpatient service
      and their parents' acculturation (categorised into high, middle and low groups).
      RESULTS: In total, 216 children, or 18.6% of the total subjects, were ill within
      the past 2 weeks and were in need of outpatient service; 94 children, or 8.1% of
      the total subjects, were in need of inpatient service. Among them, 17.6% and
      46.8% of the migrant children had unmet needs for outpatient and inpatient
      services, respectively. After controlling for enabling resources and predisposing
      characteristics, migrant children with parents in the middle-acculturation group
      (adjusted OR=3.17, 95% CIs 1.2 to 8.3, P<0.05) were more likely to have an unmet
      outpatient need than high-acculturation or low-acculturation groups, although
      only statistically significant when comparing with the high-acculturation group.
      Stratified analysis suggested that this association could be moderated by their
      family economic status. CONCLUSIONS: Our study suggested that the association
      between migrant children's health service utilisation and their parents'
      acculturation was complex and could be moderated by family economic status.
      Increasing the service utilisation among migrant children requires improving the
      acculturation and economic status of the parents of internal migrants.

PMID- 29331970
TI  - Is there a social gradient of sarcopenia? A meta-analysis and systematic review
      protocol.
AB  - INTRODUCTION: Sarcopenia (or loss of muscle mass and function) is a relatively
      new area within the field of musculoskeletal research and medicine. Investigating
      whether there is a social gradient, including occupation type and income level,
      of sarcopenia, as observed for other diseases, will contribute significantly to
      the limited evidence base for this disease. This new information may inform the
      prevention and management of sarcopenia and widen the evidence base to support
      existing and future health campaigns. METHODS AND ANALYSIS: We will conduct a
      systematic search of the databases PubMed, Ovid, CINAHL, Scopus and EMBASE to
      identify articles that investigate associations between social determinants of
      health and sarcopenia in adults aged 50 years and older. Eligibility of the
      selected studies will be determined by two independent reviewers. The
      methodological quality of eligible studies will be assessed according to
      predetermined criteria. Established statistical methods to identify and control
      for heterogeneity will be used, and where appropriate, we will conduct a meta
      analysis. In the event that heterogeneity prevents numerical synthesis, a best
      evidence analysis will be employed. This systematic review protocol adheres to
      the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols
      reporting guidelines and will be registered with the International Prospective
      Register of Systematic Reviews (PROSPERO). ETHICS AND DISSEMINATION: This
      systematic review will use published data, thus ethical permissions will not be
      required. In addition to peer-reviewed publication, our results will be presented
      at (inter)national conferences relevant to the field of sarcopenia, ageing and/or
      musculoskeletal health and disseminated both electronically and in print.
      PROSPERO REGISTRATION NUMBER: CRD42017072253.

PMID- 29331971
TI  - A study protocol for a non-randomised comparison trial evaluating the feasibility
      and effectiveness of a mobile cognitive-behavioural programme with integrated
      coaching for anxious adults in primary care.
AB  - INTRODUCTION: Generalised anxiety disorder (GAD) and subclinical GAD are highly
      prevalent in primary care. Unmanaged anxiety worsens quality of life in patients
      seen in primary care practices and leads to increased medical utilisation and
      costs. Programmes that teach patients cognitive-behavioural therapy (CBT)
      techniques have been shown to improve anxiety and to prevent the evolution of
      anxiety symptoms to disorders, but access and engagement have hampered
      integration of CBT into medical settings. METHODS AND ANALYSIS: This pragmatic
      study takes place in University of Pittsburgh Medical Center primary care
      practices to evaluate a coach-supported mobile cognitive- behavioural programme
      (Lantern) on anxiety symptoms and quality of life. Clinics were non-randomly
      assigned to either enhanced treatment as usual or Lantern. All clinics provide
      electronic screening for anxiety and, within clinics assigned to Lantern,
      patients meeting a threshold level of mild anxiety (ie, >5 on Generalised Anxiety
      Disorder 7-Item Questionnaire (GAD-7)) are referred to Lantern. The first study
      phase is aimed at establishing feasibility, acceptability and effectiveness. The
      second phase focuses on long-term impact on psychosocial outcomes, healthcare
      utilisation and clinic/provider adoption/sustainable implementation using a
      propensity score matched parallel group study design. Primary outcomes are
      changes in anxiety symptoms (GAD-7) and quality of life (Short-Form Health
      Survey) between baseline and 6-month follow-ups, comparing control and
      intervention. Secondary outcomes include provider and patient satisfaction,
      patient engagement, durability of changes in anxiety symptoms and quality of life
      over 12 months and the impact of Lantern on healthcare utilisation over 12
      months. Patients from control sites will be matched to the patients who use the
      mobile app. ETHICS AND DISSEMINATION: Ethics and human subject research approval
      were obtained. A data safety monitoring board is overseeing trial data and
      ethics. Results will be communicated to participating primary care practices,
      published and presented at clinical and scientific conferences. TRIAL
      REGISTRATION NUMBER: NCT03035019.

PMID- 29331972
TI  - Cohort profile: the Comparative Outcomes And Service Utilization Trends (COAST)
      Study among people living with and without HIV in British Columbia, Canada.
AB  - PURPOSE: The Comparative Outcomes And Service Utilization Trends (COAST) Study in
      British Columbia (BC), Canada, was designed to evaluate the determinants of
      health outcomes and health care services use among people living with HIV (PLHIV)
      as they age in the period following the introduction of combination
      antiretroviral therapy (cART). The study also assesses how age-associated
      comorbidities and health care use among PLHIV may differ from those observed in
      the general population. PARTICIPANTS: COAST was established through a data
      linkage between two provincial data sources: The BC Centre for Excellence in
      HIV/AIDS Drug Treatment Program, which centrally manages cART dispensation across
      BC and contains prospectively collected data on demographic, immunological,
      virological, cART use and other clinical information for all known PLHIV in BC;
      and Population Data BC, a provincial data repository that holds individual event
      level, longitudinal data for all 4.6 million BC residents. COAST participants
      include 13 907 HIV-positive adults (>=19 years of age) and a 10% random sample
      inclusive of 516 340 adults from the general population followed from 1996 to
      2013. FINDINGS TO DATE: For all participants, linked individual-level data
      include information on demographics, health service use (eg, inpatient care,
      outpatient care and prescription medication dispensations), mortality, and HIV
      diagnostic and clinical data. Publications from COAST have demonstrated the
      significant mortality reductions and dramatic changes in the causes of death
      among PLHIV from 1996 to 2012, differences in the amount of time spent in a
      healthy state by HIV status, and high levels of injury and mood disorder
      diagnosis among PLHIV compared with the general population. FUTURE PLANS: To
      capture the dynamic nature of population health parameters, regular data updates
      and a refresh of the data linkage are planned to occur every 2 years, providing
      the basis for planned analysis to examine age-associated comorbidities and
      patterns of health service use over time.

PMID- 29331973
TI  - Family-focused practices in addictions: a scoping review protocol.
AB  - INTRODUCTION: Families are significantly impacted by addictions and family
      involvement in treatment can reduce the harms and can also improve treatment
      entry, treatment completion and treatment outcomes for the individual coping with
      an addiction. Although the benefits of family-focused practices in addictions
      have been documented, services continue to have an individual focus and research
      on this topic is also limited. The objective of this study is to map the extent,
      range and nature of evidence available examining family interventions in
      addictions and identify gaps to guide future research, policy and practice.
      METHODS AND ANALYSIS: This is a scoping review using the five-stage framework
      developed by Arksey and O'Malley. We will include published and unpublished
      empirical studies focusing on any type of family interventions in addiction
      treatment between 2000 and the present in English or French. A reviewer will
      search for literature that meets the inclusion criteria through the following
      electronic databases: MEDLINE, PsycINFO and Social Services Abstracts. For a
      comprehensive search, we will also hand-search reference lists, web sites and key
      journals. Data will be charted and sorted using a thematic analysis approach.
      ETHICS AND DISSEMINATION: This review will be the first to examine all forms of
      family-focused practices for both substance use and problem gambling treatment
      for adults. It will provide information about existing service provisions and
      gaps in practice. This review can be used to start moving towards the development
      of best practices for families in addiction treatment. The results will be
      disseminated through a peer-reviewed journal and at mental health and addiction
      conferences.

PMID- 29331974
TI  - What are the physical and psychological health effects of suicide bereavement on
      family members? An observational and interview mixed-methods study in Ireland.
AB  - OBJECTIVES: Research focussing on the impact of suicide bereavement on family
      members' physical and psychological health is scarce. The aim of this study was
      to examine how family members have been physically and psychologically affected
      following suicide bereavement. A secondary objective of the study was to describe
      the needs of family members bereaved by suicide. DESIGN: A mixed-methods study
      was conducted, using qualitative semistructured interviews and additional
      quantitative self-report measures of depression, anxiety and stress (DASS-21).
      SETTING: Consecutive suicide cases and next-of-kin were identified by examining
      coroner's records in Cork City and County, Ireland from October 2014 to May 2016.
      PARTICIPANTS: Eighteen family members bereaved by suicide took part in a
      qualitative interview. They were recruited from the Suicide Support and
      Information System: A Case-Control Study (SSIS-ACE), where family members
      bereaved by suicide (n=33) completed structured measures of their well-being.
      RESULTS: Qualitative findings indicated three superordinate themes in relation to
      experiences following suicide bereavement: (1) co-occurrence of grief and health
      reactions; (2) disparity in supports after suicide and (3) reconstructing life
      after deceased's suicide. Initial feelings of guilt, blame, shame and anger often
      manifested in enduring physical, psychological and psychosomatic difficulties.
      Support needs were diverse and were often related to the availability or absence
      of informal support by family or friends. Quantitative results indicated that the
      proportion of respondents above the DASS-21 cut-offs respectively were 24% for
      depression, 18% for anxiety and 27% for stress. CONCLUSIONS: Healthcare
      professionals' awareness of the adverse physical and psychosomatic health
      difficulties experienced by family members bereaved by suicide is essential.
      Proactively facilitating support for this group could help to reduce the negative
      health sequelae. The effects of suicide bereavement are wide-ranging, including
      high levels of stress, depression, anxiety and physical health difficulties.

PMID- 29331975
TI  - Is postoperative bracing after pedicle screw fixation of spine fractures
      necessary? Study protocol of the ORNOT study: a randomised controlled multicentre
      trial.
AB  - INTRODUCTION: The most common surgical treatment of traumatic spine fractures is
      through a posterior approach using pedicle screws and rods. Postoperative
      treatment protocols including the use of postoperative orthoses however differ
      between hospitals and surgeons. A three-point hyperextension orthosis is designed
      to support proper posture and unload the anterior column. Some motion remains
      when wearing an orthosis, and its main value in postoperative treatment is
      therefore believed to be pain relief and patient confidence. This could
      consequently shorten recovery time. On the other hand, an orthosis could also
      lead to muscle weakness and slow down recovery. Any orthosis-related
      complications might also be avoided. Additionally, recent studies on conservative
      fracture treatment show no difference in radiological outcomes with or without an
      orthosis. To date, no randomised studies have been performed on the use of
      postoperative orthoses. METHODS AND ANALYSIS: Patients undergoing posterior
      fixation with pedicle screws for a traumatic thoracolumbar fracture (T7-L4) will
      be included in this randomised controlled multicentre non-inferiority trial.
      Forty-six patients will be randomised 1:1 to one of the two parallel groups; one
      group will wear a postoperative orthosis for 6 weeks followed by 6 weeks of
      weaning and one group will not wear an orthosis. The primary outcome is pain at 6
      weeks reported on the Numerical Rating Scale. Secondary outcomes consist of pain
      on other moments, analgesic use, complications and length of hospital stay,
      quality of life (EuroQuol 5 Dimensions), back pain-related function (Oswestry
      Disability Index) and radiological outcomes with a follow-up of 1 year. Orthosis
      compliance is monitored weekly in the orthosis group. ETHICS AND DISSEMINATION:
      The institutional review board (METc VUmc) approved this study on 11 October 2016
      under case number 2016.389. After completion of the trial, the results will be
      offered to an international scientific journal for peer-reviewed publication.
      TRIAL REGISTRATION NUMBER: NCT03097081 and NTR6285; Pre-results.

PMID- 29331976
TI  - Concealment of type 1 diabetes at work in Finland: a mixed-method study.
AB  - OBJECTIVES: To explore the possible reasons for concealing type 1 diabetes (T1D)
      at work. METHODS: The main set of data came from a cross-sectional survey
      (response rate 49.3%), the participants of which were 688 wage earners with T1D.
      Concealment of T1D was measured by asking respondents have they ever during their
      working career hidden their diabetes from their (A) colleagues and (B) line
      manager. Furthermore, semistructured interviews (n=20) were conducted to obtain
      deeper understanding. Questionnaire data were analysed using logistic regression
      analyses and qualitative interviews with inductive thematic analysis. RESULTS:
      About 30% of wage earners with T1D had concealed their condition during their
      working career from their colleagues and almost 20% from their line manager.
      Individuals aged 18-44 years age were more likely to conceal their T1D from their
      colleagues than older workers during their working career. Not disclosing T1D to
      the extended family (OR 5.24 (95% CI 2.06 to 13.35)), feeling an outsider at work
      (OR 2.47 (95% CI 1.58 to 3.84)), being embarrassed by receiving special attention
      at work (OR 1.99 (95% CI 1.33 to 2.96)) and neglecting treatment at work (OR 1.59
      (95% CI 1.01 to 2.48)) were all associated with concealment of T1D from
      colleagues. The youngest age group of 18-24 years were more likely to conceal
      their T1D from their line managers than the older age groups during their working
      career. Not disclosing T1D to the extended family (OR 4.41 (95% CI 1.72 to
      11.32)), feeling like an outsider at work (OR 2.51 (1.52 to 4.14)) and being
      embarrassed by receiving special attention at work (OR 1.81 (95% CI 1.13 to
      2.91)) were associated with concealment of T1D from line managers. From the
      interviews, five main themes related to concealment emerged, expressing fears
      related to the consequences of telling: (1) being perceived as weak, (2) job
      discrimination, (3) unwanted attention, (4) being seen as a person who uses their
      T1D for seeking advantages and (5) losing privacy. CONCLUSIONS: A considerable
      proportion of wage earners with T1D are concealing their diagnosis often because
      of feelings associated with stigma. Both overemphasis and underestimation of T1D
      at work by the colleagues or line manager may lead to concealing T1D and may thus
      be harmful to self-management of T1D. The obstacles in disclosing T1D might be
      diminished by giving adequate information at the workplace about the condition
      and its significance.

PMID- 29331977
TI  - Clinical outcomes and prognostic factors in patients with spinal dural
      arteriovenous fistulas : a prospective cohort study in two Chinese centres.
AB  - BACKGROUND: The short-term outcomes and prognostic factors of patients with
      spinal dural arteriovenous fistulas (SDAVFs) have not been defined in large
      cohorts. OBJECTIVE: To define the short-term clinical outcomes and prognostic
      factors in patients with SDAVFs. METHODS: A prospective cohort of 112 patients
      with SDAVFs were included consecutively in this study. The patients were serially
      evaluated with the modified Aminoff and Logue's Scale (mALS) one day before
      surgery and at 3 months, 6 months and 12 months after treatment. Univariate and
      multivariate analyses were performed to identify demographic, clinical and
      procedural factors related to favourable outcome. RESULTS: A total of 94 patients
      (mean age 53.5 years, 78 were men) met the criteria and are included in the final
      analyses. Duration of symptom ranged from 0.5 to 66 months (average time period
      of 12.7 months). The location of SDAVFs was as follows: 31.6% above T7 level,
      48.4% between T7 and T12 level (including T7 and T12) and 20.0% below T12 level.
      A total of 81 patients (86.2%) underwent neurosurgical treatment, 10 patients
      (10.6%) underwent endovascular treatment, and 3 patients (3.2%) underwent
      neurosurgical treatment after unsuccessful embolisation. A total of 78 patients
      demonstrated an improvement in mALS score of one point or greater at 12 months.
      Preoperative mALS score was associated with clinical improvement after adjusting
      for age, gender, duration of symptoms, location of fistula and treatment modality
      using unconditional logistic regression analysis (p<0.05). CONCLUSION:
      Approximately four fifths of the patients experienced clinical improvement at 12
      months and preoperative mALS was the strongest predictor of clinical improvement
      in the cohort.

PMID- 29331978
TI  - Postdischarge service utilisation and outcomes among Chinese and South Asian
      psychiatric inpatients in Ontario, Canada: a population-based cohort study.
AB  - OBJECTIVE: We sought to examine the short-term and long-term impacts of
      psychiatric hospitalisations among patients of Chinese and South Asian origin.
      DESIGN: Retrospective population-based cohort study using linked health
      administrative data. SETTING: We examined all adult psychiatric inpatients
      discharged between 1 April 2006 and 31 March 2014 in Ontario, Canada, who were
      classified as Chinese, South Asian and all other ethnicities (ie, 'general
      population') using a validated algorithm. We identified 2552 Chinese, 2439 South
      Asian and 127 142 general population patients. PRIMARY AND SECONDARY OUTCOME
      MEASURES: We examined psychiatric severity measures at admission and discharge
      and performed multivariable logistic regression analyses to examine 30-day, 180
      day and 365-day postdischarge service utilisation and outcomes, comparing each of
      the ethnic groups with the reference population, after adjustment for age, sex,
      income, education, marital status, immigration status, community size and
      discharge diagnosis. RESULTS: Despite presenting to hospital with greater illness
      severity, Asian psychiatric inpatients had shorter lengths of hospital stay and
      greater absolute improvements in mental health and functional status at discharge
      compared with other inpatients. After hospitalisation, Chinese patients were more
      likely to visit psychiatrists and South Asian patients were more likely to seek
      mental healthcare from general practitioners. They were also less likely to have
      a psychiatric readmission or die 1 year following hospitalisation (adjusted
      ORChinese=0.87; 95% CI 0.79 to 0.97; adjusted ORSouth Asian=0.82, 95% CI 0.73 to
      0.91). Findings were consistent across genders, psychiatric diagnoses and
      immigrant groups. CONCLUSION: Once hospitalised, patients of Chinese and South
      Asian origin fared as well as or better than general population patients at
      discharge and following discharge, and had a positive trajectory of psychiatric
      service utilisation.

PMID- 29331979
TI  - Now you see me: a pragmatic cohort study comparing first and final radiological
      diagnoses in the emergency department.
AB  - OBJECTIVES: To (1) compare timely but preliminary and definitive but delayed
      radiological reports in a large urban level 1 trauma centre, (2) assess the
      clinical significance of their differences and (3) identify clinical predictors
      of such differences. DESIGN, SETTING AND PARTICIPANTS: We performed a
      retrospective record review for all 2914 patients who presented to our university
      affiliated emergency department (ED) during a 6-week period. In those that
      underwent radiological imaging, we compared the patients' discharge letter from
      the ED to the definitive radiological report. All identified discrepancies were
      assessed regarding their clinical significance by trained raters, independent and
      in duplicate. A binary logistic regression was performed to calculate the
      likelihood of discrepancies based on readily available clinical data. RESULTS:
      1522 patients had radiographic examinations performed. Rater agreement on the
      clinical significance of identified discrepancies was substantial (kappa=0.86).
      We found an overall discrepancy rate of 20.35% of which about one-third (7.48%
      overall) are clinically relevant. A logistic regression identified patients' age,
      the imaging modality and the anatomic region under investigation to be predictive
      of future discrepancies. CONCLUSIONS: Discrepancies between radiological
      diagnoses in the ED are frequent and readily available clinical factors predict
      their likelihood. Emergency physicians should reconsider their discharge
      diagnosis especially in older patients undergoing CT scans of more than one
      anatomic region.

PMID- 29331980
TI  - DMC1 mutation that causes human non-obstructive azoospermia and premature ovarian
      insufficiency identified by whole-exome sequencing.
AB  - BACKGROUND: The genetic causes of the majority of male and female infertility
      caused by human non-obstructive azoospermia (NOA) and premature ovarian
      insufficiency (POI) with meiotic arrest are unknown. OBJECTIVE: To identify the
      genetic cause of NOA and POI in two affected members from a consanguineous
      Chinese family. METHODS: We performed whole-exome sequencing of DNA from both
      affected patients. The identified candidate causative gene was further verified
      by Sanger sequencing for pedigree analysis in this family. In silico analysis was
      performed to functionally characterise the mutation, and histological analysis
      was performed using the biopsied testicle sample from the male patient with NOA.
      RESULTS: We identified a novel homozygous missense mutation (NM_007068.3:
      c.106G>A, p.Asp36Asn) in DMC1, which cosegregated with NOA and POI phenotypes in
      this family. The identified missense mutation resulted in the substitution of a
      conserved aspartic residue with asparaginate in the modified H3TH motif of DMC1.
      This substitution results in protein misfolding. Histological analysis
      demonstrated a lack of spermatozoa in the male patient's seminiferous tubules.
      Immunohistochemistry using a testis biopsy sample from the male patient showed
      that spermatogenesis was blocked at the zygotene stage during meiotic prophase I.
      CONCLUSIONS: To the best of our knowledge, this is the first report identifying
      DMC1 as the causative gene for human NOA and POI. Furthermore, our pedigree
      analysis shows an autosomal recessive mode of inheritance for NOA and POI caused
      by DMC1 in this family.

PMID- 29331981
TI  - Variant in C-terminal region of intestinal alkaline phosphatase associated with
      benign familial hyperphosphatasaemia.
AB  - BACKGROUND: A genetic diagnosis has been rarely performed in benign familial
      hyperphosphatasaemia, and molecular mechanism largely remains unclear.
      OBJECTIVES: We encountered a case with benign familial hyperphosphatasaemia of
      intestinal alkaline phosphatase (IAP). To elucidate the molecular mechanism, we
      performed ALPI gene sequencing and in vitro protein expression analysis. METHODS:
      ALPI gene was sequenced by long-range PCR and massively parallel sequencing. The
      soluble and membrane-bound ALP activities of the cultured cell line, transfected
      with the wild-type or variant-type ALPI gene were analysed by a
      glycosylphosphatidylinositol (GPI)-cleaving assay. RESULTS: We identified a
      deletion-insertion variant in the C-terminal end of the ALPI gene. This variant
      causes the attenuation of the hydrophobicity in GPI-anchor signal of IAP. An in
      vitro GPI-cleaving assay demonstrated that the membrane-bound IAP was greatly
      decreased, whereas the soluble IAP was increased, in the variant IAP.
      CONCLUSIONS: The C-terminal variant in ALPI causes the benign familial
      hyperphosphatasaemia of IAP by the attenuation of the membrane-binding
      capability.

PMID- 29331982
TI  - A false-carrier state for the c.579G>A mutation in the NCF1 gene in Ashkenazi
      Jews.
AB  - BACKGROUND: Mutations in the NCF1 gene that encodes p47phox, a subunit of the
      NADPH oxidase complex, cause chronic granulomatous disease (CGD). In Kavkazi
      Jews, a c.579G>A (p.Trp193Ter) mutation in NCF1 is frequently found, leading to
      CGD. The same mutation is found in about 1% of Ashkenazi Jews, although Ashkenazi
      CGD patients with this mutation have never been described. METHODS: We used
      Sanger sequencing, multiplex ligation-dependent probe amplification (MLPA), gene
      scan analysis and Ion Torrent Next Generation Sequencing for genetic analysis,
      and measured NADPH oxidase activity and p47phox expression. RESULTS: In an
      Ashkenazi couple expecting a baby, both parents were found to be heterozygotes
      for this mutation, as was the fetus. However, segregation analysis in the
      extended family was consistent with the fetus inheriting both carrier alleles
      from the parents. MLPA indicated four complete NCF1 genes in the fetus and three
      in each parent. Gene sequencing confirmed these results. Analysis of fetal
      leucocytes obtained by cordocentesis revealed substantial oxidase activity with
      three different assays, which was confirmed after birth. In six additional
      Ashkenazi carriers of the NCF1 c.579G>A mutation, we found five individuals with
      three complete NCF1 genes of which one was mutated (like the parents), and one
      individual with in addition a fusion gene of NCF1 with a pseudogene. CONCLUSION:
      These results point to the existence of a 'false-carrier' state in Ashkenazi Jews
      and have wide implications regarding pre-pregnancy screening in this and other
      population groups.

PMID- 29331983
TI  - Ophthalmoscopy skills in primary care: a cross-sectional practitioner survey.

PMID- 29331984
TI  - Response to: 'Psychosocial job stressors and suicidality: a meta-analysis and
      systematic review' by Milner et al.

PMID- 29331985
TI  - Repair for rheumatic mitral valve disease. The controversy goes on!

PMID- 29331989
TI  - Learning framework for implementing best evidence.

PMID- 29331988
TI  - Airflow limitation in people living with HIV and matched uninfected controls.
AB  - INTRODUCTION: Whether HIV influences pulmonary function remains controversial. We
      assessed dynamic pulmonary function in people living with HIV (PLWHIV) and
      uninfected controls. METHODS: A total of 1098 PLWHIV from the Copenhagen Co
      morbidity in HIV infection study and 12 161 age-matched and sex-matched controls
      from the Copenhagen General Population Study were included. Lung function was
      assessed using FEV1 and FVC, while airflow limitation was defined by the lower
      limit of normal (LLN) of FEV1/FVC and by FEV1/FVC<0.7 with FEV1predicted <80%
      (fixed). Logistic and linear regression models were used to determine the
      association between HIV and pulmonary function adjusting for potential
      confounders (including smoking and socioeconomic status). RESULTS: In
      predominantly white men with mean (SD) age of 50.6 (11.1) the prevalence of
      airflow limitation (LLN) was 10.6% (95% CI 8.9% to 12.6%) in PLWHIV and 10.6%
      (95% CI 10.0 to 11.1) in uninfected controls. The multivariable adjusted OR for
      airflow limitation defined by LLN for HIV was 0.97 (0.77-1.21, P<0.78) and 1.71
      (1.34-2.16, P<0.0001) when defined by the fixed criteria. We found no evidence of
      interaction between HIV and cumulative smoking in these models (P interaction:
      0.25 and 0.17 for LLN and fixed criteria, respectively). HIV was independently
      associated with 197 mL (152-242, P<0.0001) lower FEV1 and 395 mL (344-447,
      P<0.0001) lower FVC, and 100 cells/mm3 lower CD4 nadir was associated with 30 mL
      (7-52, P<0.01) lower FEV1 and 51 mL (24-78, P<0.001) lower FVC. CONCLUSION: HIV
      is a risk factor for concurrently decreased FEV1 and FVC. This excess risk is not
      explained by smoking or socioeconomic status and may be mediated by prior
      immunodeficiency. TRIAL REGISTRATION NUMBER: NCT02382822.

PMID- 29331986
TI  - Sex differences in impact of coronary artery calcification to predict coronary
      artery disease.
AB  - OBJECTIVE: To assess sex-specific differences regarding use of conventional risks
      and coronary artery calcification (CAC) to detect coronary artery disease (CAD)
      using coronary CT angiography (CCTA). METHODS: The Nationwide Gender-specific
      Atherosclerosis Determinants Estimation and Ischemic Cardiovascular Disease
      Prospective Cohort study is a prospective, multicentre, nationwide cohort study.
      Candidates with suspected CAD aged 50-74 years enrolled from 2008 to 2012. The
      outcome was obstructive CAD defined as any stenosis >=50% by CCTA. We constructed
      logistic regression models for obstructive CAD adjusted for conventional risks
      (clinical model) and CAC score. Improvement in discrimination beyond risks was
      assessed by C-statistic; net reclassification index (NRI) for CAD probability of
      low (<30%), intermediate (30%-60%) and high (>=60%); and risk stratification
      capacity. RESULTS: Among 991 patients (456 women, 535 men; 65.2 vs 64.4 years
      old), women had lower CAC scores (median, 4 vs 60) and lower CAD prevalence
      (21.7% vs 37.0%) than men. CAC significantly improved model discrimination
      compared with clinical model in both sexes (0.66-0.79 in women vs 0.61-0.83 in
      men). The NRI for women was 0.33, which was much lower than that for men (0.71).
      Adding CAC to clinical model had a larger benefit in terms of moving an
      additional 43.3% of men to the most determinant categories (high or low risk)
      compared with -1.4% of women. CONCLUSIONS: The addition of CAC to a prediction
      model based on conventional variables significantly improved the classification
      of risk in suspected patients with CAD, with sex differences influencing the
      predictive ability. TRIAL REGISTRATION NUMBER: UMIN-CTR Clinical Trial:
      UMIN000001577.

PMID- 29331990
TI  - Changes in the legal environment and enforcement of firearm transfer laws in
      Pennsylvania and Maryland.
AB  - The effectiveness of laws depends on circumstances affecting their enforcement.
      To assess such circumstances for comprehensive background check (CBC) and straw
      purchase laws for firearm sales, we examined prosecutions for CBC and straw
      purchase violations in Pennsylvania and CBC violations in Maryland. We generated
      pre-post variables and conducted t-tests to assess differences in the mean number
      of prosecutions filed following changes to the legal environments. The annual
      number of prosecutions for straw purchase violations increased significantly in
      Pennsylvania following the passage of a law that strengthened penalties for these
      violations (difference in means = +1310.86, P=0.003). The annual number of
      prosecutions for CBC violations decreased significantly in Maryland following a
      court decision that narrowed the definition of a firearm transfer making
      enforcement more difficult (difference in means = -20.52, P=0.026). Our findings
      suggest enforcement is likely influenced by the penalties associated with
      violating these laws and the interpretation of the language of the laws.

PMID- 29331991
TI  - Gauging the impact of gun background checks.

PMID- 29331992
TI  - Effectiveness of interventions for reducing non-occupational sedentary behaviour
      in adults and older adults: a systematic review and meta-analysis.
AB  - BACKGROUND: No systematic reviews of the effectiveness of interventions for
      reducing non-occupational sedentary behaviour are available. Therefore, the aim
      of this systematic review was to assess the effectiveness of interventions for
      reducing non-occupational sedentary behaviour in adults and older adults.
      METHODS: An electronic search of nine databases was performed. Randomised
      controlled trials (RCT) and cluster RCTs among adults testing the effectiveness
      of interventions aimed to reduce non-occupational sedentary behaviour were
      considered for inclusion. Two review authors independently screened studies for
      eligibility, completed data extraction and assessed the risk of bias. RESULTS:
      Nineteen studies that evaluated multicomponent lifestyle interventions,
      counselling or education, television (TV) control devices and workplace
      interventions were included. Evidence from the meta-analyses suggested that
      interventions can reduce leisure sitting time in adults in the medium term (-30
      min/day; 95% CI -58 to -2), and TV viewing in the short term (-61 min/day; 95% CI
      -79 to -43) and medium term (-11 min/day; 95% CI -20 to -2). No significant
      pooled effects were found for transport sitting time, leisure-time computer use
      and longer term outcomes. No evidence was available on the effectiveness of
      interventions for reducing non-occupational sedentary time in older adults.
      CONCLUSIONS: The findings of this systematic review suggest the interventions may
      be effective in reducing non-occupational sedentary behaviour in the short to
      medium term in adults. However, no significant effect was found on longer term
      outcomes. The quality of evidence was, however, low to very low. No evidence was
      available on the effectiveness of non-occupational interventions on reducing
      sedentary time in older adults. Further high-quality research with larger samples
      is warranted.

PMID- 29331993
TI  - Increased leisure-time physical activity associated with lower onset of diabetes
      in 44 828 adults with impaired fasting glucose: a population-based prospective
      cohort study.
AB  - AIMS: To evaluate the effects of habitual leisure-time physical activity (LTPA)
      on incident type 2 diabetes in a prospective cohort of Chinese adults with
      impaired fasting glucose (IFG). METHODS: 44 828 Chinese adults aged 20-80 years
      with newly detected IFG but free from cardiovascular and cerebrovascular disease
      were recruited and followed up from 1996 to 2014. Incident type 2 diabetes was
      identified by fasting plasma glucose >=7 mmol/L. The participants were classified
      into four categories based on their self-reported weekly LTPA: inactive, low,
      moderate, or high. Hazard ratios (HRs) and population attributable fractions
      (PAFs) were estimated with adjustment for established diabetic risk factor.
      RESULTS: After 214 148 person-years of follow-up, we observed an inverse dose
      response relationship between LTPA and diabetes risk. Compared with inactive
      participants, diabetes risk in individuals reporting low, moderate and high
      volume LTPA were reduced by 12% (HR 0.88, 95% CI 0.80 to 0.99; P=0.015), 20% (HR
      0.80, 95% CI 0.71 to 0.90; P<0.001), and 25% (HR 0.75, 95% CI 0.67 to 0.83;
      P<0.001), respectively. At least 19.2% (PAF 19.2%, 95% CI 5.9% to 30.6%) of
      incident diabetes cases could be avoided if the inactive participants had engaged
      in WHO recommendation levels of LTPA. This would correspond to a potential
      reduction of at least 7 million diabetic patients in the Greater China area.
      CONCLUSIONS: Our results show higher levels of LTPA are associated with a lower
      risk of diabetes in IFG subjects. These data emphasise the urgent need for
      promoting physical activity as a preventive strategy against diabetes to offset
      the impact of population ageing and the growing obesity epidemic.

PMID- 29331994
TI  - ACL and meniscal injuries increase the risk of primary total knee replacement for
      osteoarthritis: a matched case-control study using the Clinical Practice Research
      Datalink (CPRD).
AB  - OBJECTIVES: The aim of this study was to investigate whether ACL injury (ACLi) or
      meniscal injury increases the risk of end-stage osteoarthritis (OA) resulting in
      total knee replacement (TKR). METHODS: A matched case-control study of all TKRs
      performed in the UK between January 1990 and July 2011 and recorded in the
      Clinical Practice Research Datalink (CPRD) was undertaken. The CPRD contains
      longitudinal data on approximately 3.6 million patients. Two controls were
      selected for each case of TKR, matched on age, sex and general practitioner
      location as a proxy for socioeconomic status. Individuals with inflammatory
      arthritis were excluded. The odds of having TKR for individuals with a CPRD
      recorded ACLi were compared with those without ACLi using conditional logistic
      regression, after adjustment for body mass index, previous knee fracture and
      meniscal injury. The adjusted odds of TKR in individuals with a recorded meniscal
      injury compared with those without were calculated. RESULTS: After exclusion of
      individuals with inflammatory arthritis, there were 49 723 in the case group and
      104 353 controls. 153 (0.31%) cases had a history of ACLi compared with 41
      (0.04%) controls. The adjusted OR of TKR after ACLi was 6.96 (95% CI 4.73 to
      10.31). 4217 (8.48%) individuals in the TKR group had a recorded meniscal injury
      compared with 669 (0.64%) controls. The adjusted OR of TKR after meniscal injury
      was 15.24 (95% CI 13.88 to 16.69). CONCLUSION: This study demonstrates that ACLi
      is associated with a sevenfold increased odds of TKR resulting from OA. Meniscal
      injury is associated with a 15-fold increase odds of TKR for OA.

PMID- 29331995
TI  - Infographic: Trends in paediatric and adolescent ACL injuries.

PMID- 29331997
TI  - Correction: A rare case of dual diagnosis in a 16-year-old girl with shortness of
      breath.

PMID- 29331996
TI  - Relevance of enlarged cardiophrenic lymph nodes in determining prognosis of
      patients with advanced ovarian cancer.
AB  - Ovarian cancer often presents at an advanced stage with widespread peritoneal
      and/or extra-abdominal metastases. Complete cytoreduction is the mainstay of
      treatment for disease confined to peritoneum. But in patients with distant
      metastases, the role and rationale is less obvious. One of the the most common
      sites of extra-abdominal disease is the cardiophrenic lymph node (CPLN). In this
      paper, we described the management of a patient with International Federation of
      Gynecology and Obstetrics (FIGO) stage IVB epithelial ovarian carcinoma and
      widespread peritoneal and extra-abdominal metastases to the CPLN, who underwent
      complete cytoreduction including excision of enlarged CPLN, following neoadjuvant
      chemotherapy. We examined the literature to determine the prognostic value of
      enlarged CPLN and their relevance in managing patients with advanced ovarian
      cancer and found it as an adverse prognostic factor. Transdiaphragmatic excision
      of CPLN is feasible without major complications. But as its correlation with
      overall or progression-free survival is not yet evident, large-scale prospective
      studies are warranted.

PMID- 29331998
TI  - Torsion and rupture of a non-communicating rudimentary horn in a 17-week
      gestation in a 16-year-old girl: lessons learnt.
AB  - A unicornuate uterus with non-communicating rudimentary horn has always been
      notorious and poses threat to continuation of pregnancy with dismal consequences.
      We are reporting an interesting case of uterine malformation with a 90 degrees 
      rotation of uterine axis which ultimately ruptured during termination of
      pregnancy. The rarity in our case was not only conception in non-communicating
      horn but also the complete twisting of axis which made the pregnant horn come in
      front of the non-gravid unicornuate uterus, mimicking normal pregnancy. The most
      important lesson learnt is that if induction does not lead to cervical changes
      and uterine contractions, one must consider atypical presentations of an
      anomalous uterus as a possible differential before proceeding further.

PMID- 29331999
TI  - Eighty-five-year-old man with mosaic attenuation on chest imaging.

PMID- 29332000
TI  - How good are doctors at introducing themselves? #hellomynameis.
AB  - BACKGROUND: This explorative study was triggered by the '#hellomynameis' campaign
      initiated by Dr Kate Granger in the UK. Our objectives were twofold: first, to
      measure rates of introduction in an Irish hospital setting by both consultant and
      non-consultant hospital doctors. Second to establish whether such practices were
      associated with patient perceptions of the doctor/patient interaction. METHOD: A
      patient 'exit' survey was undertaken following doctor-patient consultations in
      both acute (surgical and medical assessment units) and elective settings
      (outpatient clinics). The survey was carried out over a 5-month period by three
      trained clinical observers. RESULTS: A total of 353 patients were surveyed. There
      were 253 outpatients and 100 inpatients surveyed. There were 121 outpatients
      (47.8%) who attended a surgeon, 73 were medical (28.8%), while 59 (23.3%) were
      divided between obstetrics, gynaecology and ophthalmology. One hundred acute
      presentations were surveyed: 52% in the emergency department, 20% to the acute
      medical assessment unit, 21% attended the acute surgical assessment unit and 7%
      attended other specialties/departments. CONCLUSION: According to the returned
      forms, 79% of doctors (n=279) introduced themselves to patients. Eleven per cent
      (39) of doctors did not introduce themselves, and 8.5% of patients (30) were
      unsure whether the doctor had introduced themselves. Five patients left their
      response blank.Consultants were significantly more likely (P=0.02) to introduce
      themselves or shake hands than non-consultant hospital doctors. Gender had no
      bearing (P=0.43) on introductions or handshakes regardless of grade of
      doctor.Three hundred and seventeen patients (89.7%) felt that an introduction had
      made a positive difference to their healthcare visit. Thirty patients (8.5%) felt
      it did not make a difference and 8 patients (2.2%) were unsure or failed to
      answer.This study has highlighted the importance of introductions to patients.
      Definite evidence of an introduction was documented in 79% of patients with 14.5%
      either not receiving or could not recall whether an introduction had been made on
      repeat visits. 6.5% stated that they did not receive an introduction.

PMID- 29332001
TI  - Problem-solving in clinical practice: a baby who won't stop bleeding.
AB  - Spontaneous bleeding in the neonatal period is an unusual presentation, and yet
      one that can pose a challenge of both diagnosis and management to the general
      paediatrician. This case chronicles the diagnostic journey of an 8-day-old baby
      who presented with unrelenting bleeding from the umbilical cord and explores the
      clinical approach to bleeding in a neonate.

PMID- 29332003
TI  - What do I need to know about metronidazole?

PMID- 29332002
TI  - The implementation of a cystic fibrosis annual review process in a tertiary
      paediatric hospital.
AB  - We evaluated the implementation of a cystic fibrosis annual review process in a
      tertiary paediatric hospital. After implementation, there was demonstrated
      improvement in an important outcome measure-the use of inhaled mucolytic agents.

PMID- 29332004
TI  - Host-agent-vector-environment measures for electronic cigarette research used in
      NIH grants.
AB  - OBJECTIVE: The purpose of this study is to describe the focus and
      comprehensiveness of domains measured in e-cigarette research. METHODS: A
      portfolio analysis of National Institutes of Health grants focusing on e
      cigarette research and funded between the fiscal years 2007 and 2015 was
      conducted. Grant proposals were retrieved using a government database and coded
      using the Host-Agent-Vector-Environment (HAVE) model as a framework to
      characterise the measures proposed. Eighty-one projects met the criteria for
      inclusion in the analysis. RESULTS: The primary HAVE focus most commonly found
      was Host (73%), followed by Agent (21%), Vector (6%) and Environment (0%).
      Intrapersonal measures and use trajectories were the most common measures in
      studies that include Host measures (n=59 and n=51, respectively). Product
      composition was the most common area of measurement in Agent studies (n=24),
      whereas Marketing (n=21) was the most common (n=21) area of Vector measurement.
      When Environment measures were examined as secondary measures in studies, they
      primarily focused on measuring Peer, Occupation and Social Networks (n=18).
      Although all studies mentioned research on e-cigarettes, most (n=52; 64%) did not
      specify the type of e-cigarette device or liquid solution under study.
      CONCLUSIONS: This analysis revealed a heavy focus on Host measures (73%) and a
      lack of focus on Environment measures. The predominant focus on Host measures may
      have the unintended effect of limiting the evidence base for tobacco control and
      regulatory science. Further, a lack of specificity about the e-cigarette product
      under study will make comparing results across studies and using the outcomes to
      inform tobacco policy difficult.

PMID- 29332005
TI  - Impact of a negative emotional antitobacco mass media campaign on French smokers:
      a longitudinal study.
AB  - BACKGROUND: Mass media campaigns to encourage smoking cessation have been shown
      to be effective in a context of comprehensive tobacco control programme. The
      effectiveness of antismoking ads that evoke negative emotions remains unclear, in
      particular in countries with high smoking prevalence and among smokers with low
      perceived susceptibility, low self-efficacy or who are not users of smoking
      cessation services. OBJECTIVE: To evaluate short-term and long-term effects of a
      1-month French national highly emotional media campaign, with a focus on these
      specific targets. DESIGN: A 6-month longitudinal survey by Internet. A sample of
      3000 smokers were interviewed before the media campaign (T0). They were contacted
      again just after (T1) and 6 months after the campaign (T2). OUTCOMES: Perceived
      susceptibility to the risks of smoking, self-efficacy to quit smoking, use of
      smoking cessation services (quitline and website) and 7-day quitting. METHODS:
      The analysis was carried out on 2241 individuals who answered at T1 and T2.
      Multiple logistic regressions were computed to test the association between the
      change in each outcome at T1 and T2 and the level of exposure based on self
      reported recall. RESULTS: Self-reported recall was associated with an increase in
      perceived susceptibility and with use of cessation services. Campaign recall was
      also associated with higher 7-day quitting immediately after the campaign (OR=1.8
      (1.0 to 3.2), P<0.05). CONCLUSIONS: Fear-appeal mass media campaigns can be
      effective in encouraging cessation among smokers in a country with high smoking
      prevalence (France), but should be accompanied by convincing self-efficacy
      messages.

PMID- 29332006
TI  - Global evidence on the effect of point-of-sale display bans on smoking
      prevalence.
AB  - BACKGROUND: Since Iceland became the first country to impose a ban on point-of
      sale (POS) tobacco product displays in 2001, 20 countries have implemented POS
      display bans as of 2016. This study examined the effect that POS display bans
      have on smoking prevalence. METHODS: Data were sourced from Euromonitor
      International and the WHO MPOWER package for 2007-2014 from 77 countries
      worldwide. generalised linear models with country and year fixed effects were
      estimated to analyse the effect of POS display bans on smoking prevalence.
      RESULTS: Having a POS display ban reduced overall adult daily smoking, male
      smoking and female smoking by about 7%, 6% and 9%, respectively. CONCLUSIONS:
      Having a POS display ban is likely to reduce smoking prevalence and generate
      public health benefits.

PMID- 29332007
TI  - Impacts of Canada's minimum age for tobacco sales (MATS) laws on youth smoking
      behaviour, 2000-2014.
AB  - BACKGROUND: Recently, the US Institute of Medicine has proposed that raising the
      minimum age for tobacco purchasing/sales to 21 years would likely lead to
      reductions in smoking behavior among young people. Surprisingly few studies,
      however, have assessed the potential impacts of minimum-age tobacco restrictions
      on youth smoking. OBJECTIVE: To estimate the impacts of Canadian minimum age for
      tobacco sales (MATS) laws on youth smoking behaviour. DESIGN: A regression
      discontinuity design, using seven merged cycles of the Canadian Community Health
      Survey, 2000-2014. PARTICIPANTS: Survey respondents aged 14-22 years (n=98 320).
      EXPOSURE: Current Canadian MATS laws are 18 years in Alberta, Saskatchewan,
      Manitoba, Quebec, the Yukon and Northwest Territories, and 19 years of age in the
      rest of the country. MAIN OUTCOMES: Current, occasional and daily smoking status;
      smoking frequency and intensity; and average monthly cigarette consumption.
      RESULTS: In comparison to age groups slightly younger than the MATS, those just
      older had significant and abrupt increases immediately after the MATS in the
      prevalence of current smokers (absolute increase: 2.71%; 95% CI 0.70% to 4.80%;
      P=0.009) and daily smokers (absolute increase: 2.43%; 95% CI 0.74% to 4.12%;
      P=0.005). Average past-month cigarette consumption within age groups increased
      immediately following the MATS by 18% (95% CI 3% to 39%; P=0.02). There was no
      evidence of significant increases in smoking intensity for daily or occasional
      smokers after release from MATS restrictions. CONCLUSION: The study provides
      relevant evidence supporting the effectiveness of Canadian MATS laws for limiting
      smoking among tobacco-restricted youth.

PMID- 29332008
TI  - Leg stereotypy syndrome: phenomenology and prevalence.
AB  - OBJECTIVES: To describe the phenomenology and prevalence of leg stereotypy
      syndrome (LSS), characterised chiefly by repetitive, rhythmical, stereotypic leg
      movement, especially when sitting. METHODS: We sought to characterise LSS in two
      groups of subjects: (1) general population (GP) group, defined as individuals
      accompanying patients during their visits to Baylor College of Medicine
      Parkinson's Disease Center and Movement Disorders Clinic who are not genetically
      related to the patients; and (2) movement disorders (MD) group, composed of
      consecutive patients with diagnoses of restless legs syndrome, Parkinson's
      disease, Tourette syndrome and tardive dyskinesia. RESULTS: There were 92
      participants enrolled in this study; 7% of 57 individuals in the GP group and 17%
      of those in the MD group met the diagnostic criteria for LSS. The mean age of
      individuals with LSS was 44.5 (+/-11.9) years and mean age at onset of LSS was
      17.5 (+/-5.7) years. In half of the individuals, the 'shaking' involved
      predominantly one leg. All had a positive family history of similar disorder and
      none had diurnal variation. The seven-item Leg Stereotypy Syndrome Questionnaire
      was developed as a screening tool to aid in differentiating LSS from other
      movement disorders. CONCLUSIONS: LSS is a common condition, occurring in up to 7%
      of otherwise healthy individuals, and it is even more common in patients with
      hyperkinetic movement disorders. Although it phenomenologically may overlap with
      other stereotypic disorders, we argue that it is a distinct, familial,
      neurological syndrome.

PMID- 29332009
TI  - Poststroke psychosis: a systematic review.
AB  - A preregistered systematic review of poststroke psychosis examining clinical
      characteristics, prevalence, diagnostic procedures, lesion location, treatments,
      risk factors and outcome. Neuropsychiatric outcomes following stroke are common
      and severely impact quality of life. No previous reviews have focused on
      poststroke psychosis despite clear clinical need. CINAHL, MEDLINE and PsychINFO
      were searched for studies on poststroke psychosis published between 1975 and
      2016. Reviewers independently selected studies for inclusion, extracted data and
      rated study quality. Out of 2442 references, 76 met inclusion criteria. Average
      age for poststroke psychosis was 66.6 years with slightly more males than females
      affected. Delayed onset was common. Neurological presentation was typical for
      stroke, but a significant minority had otherwise 'silent strokes'. The most
      common psychosis was delusional disorder, followed by schizophrenia-like
      psychosis and mood disorder with psychotic features. Estimated delusion
      prevalence was 4.67% (95% CI 2.30% to 7.79%) and hallucinations 5.05% (95% CI
      1.84% to 9.65%). Twelve-year incidence was 6.7%. No systematic treatment studies
      were found. Case studies frequently report symptom remission after
      antipsychotics, but serious concerns about under-representation of poor outcome
      remain. Lesions were typically right hemisphere, particularly frontal, temporal
      and parietal regions, and the right caudate nucleus. In general, poststroke
      psychosis was associated with poor functional outcomes and high mortality. Poor
      methodological quality of studies was a significant limitation. Psychosis
      considerably adds to illness burden of stroke. Delayed onset suggests a window
      for early intervention. Studies on the safety and efficacy of antipsychotics in
      this population are urgently needed.

PMID- 29332010
TI  - Oligogenic genetic variation of neurodegenerative disease genes in 980 postmortem
      human brains.
AB  - BACKGROUND: Several studies suggest that multiple rare genetic variants in genes
      causing monogenic forms of neurodegenerative disorders interact synergistically
      to increase disease risk or reduce the age of onset, but these studies have not
      been validated in large sporadic case series. METHODS: We analysed 980
      neuropathologically characterised human brains with Alzheimer's disease (AD),
      Parkinson's disease-dementia with Lewy bodies (PD-DLB), frontotemporal dementia
      amyotrophic lateral sclerosis (FTD-ALS) and age-matched controls. Genetic
      variants were assessed using the American College of Medical Genetics criteria
      for pathogenicity. Individuals with two or more variants within a relevant
      disease gene panel were defined as 'oligogenic'. RESULTS: The majority of
      oligogenic variant combinations consisted of a highly penetrant allele or known
      risk factor in combination with another rare but likely benign allele. The
      presence of oligogenic variants did not influence the age of onset or disease
      severity. After controlling for the single known major risk allele, the frequency
      of oligogenic variants was no different between cases and controls. CONCLUSIONS:
      A priori, individuals with AD, PD-DLB and FTD-ALS are more likely to harbour a
      known genetic risk factor, and it is the burden of these variants in combination
      with rare benign alleles that is likely to be responsible for some oligogenic
      associations. Controlling for this bias is essential in studies investigating a
      potential role for oligogenic variation in neurodegenerative diseases.

PMID- 29332011
TI  - Examining the utility of cystatin C as a confirmatory test of chronic kidney
      disease across the age range in middle-aged and older community-dwelling adults.
AB  - BACKGROUND: Cystatin C has been proposed as a confirmatory test of chronic kidney
      disease (CKD). This is most applicable to older individuals with CKD, the
      majority of whom have a creatinine-based estimated glomerular filtration rate
      (eGFR) of 45-59 mL/min/1.73 m2 (CKD stage 3a). We sought to examine the utility
      of cystatin C as a confirmatory test of CKD across the age range in the general
      population of older adults. METHODS: Cross-sectional analysis of 5386
      participants from The Irish Longitudinal Study on Ageing, a cluster-sampled
      national cohort of community-dwelling adults aged >=50 years. Cystatin C and
      creatinine were measured simultaneously using standardised assays. Using
      generalised additive models, we modelled the distributions of creatinine and
      cystatin C per year of age from four distributional parameters: location,
      dispersion, skewness, kurtosis. Among participants with CKD stage 3a, we
      estimated the predicted probability of cystatin C eGFR <60 mL/min/1.73 m2
      ('confirmed CKD') as a function of age. RESULTS: Median age was 62 years, 53%
      were female and median cystatin C eGFR was 80 mL/min/1.73 m2. We observed
      progressive variability in cystatin C with increasing age. Compared with
      creatinine, cystatin C levels rose sharply beyond the age of 65. Among
      participants with CKD stage 3a (n=463), the predicted probability of 'confirmed
      CKD' increased steadily with age, from 15% at age 50 to 80% at age 80.
      CONCLUSIONS: The clinical utility of cystatin C may be maximised in middle-aged
      individuals, in whom the distribution of cystatin C is less variable than older
      adults, and the pretest probability of confirming CKD is lower.

PMID- 29332013
TI  - Patterns and predictors of disclosure of HIV positive status among youth living
      with HIV in Ibadan, Nigeria.
AB  - Background Information on disclosure of HIV status among youth is sparse in spite
      of the fact that they bear a significant burden of the HIV epidemic. Our
      objective was to determine the predictors of HIV disclosure among youth aged 18
      35 years in Ibadan, Nigeria. Methods A cross-sectional study was conducted among
      youth with HIV attending two HIV support groups and one ARV clinic in Ibadan,
      Nigeria. Information was obtained with the aid of an interviewer-administered
      questionnaire. Descriptive and analytic statistics were conducted. Results There
      were 170 clients with a mean age of 29.6 +/- 3.9 years; 140 (82.4%) were female
      and 139 (81.8%) had disclosed their status. Common people first informed included
      respondents' mother 49 (35.3%), spouse 39 (28.1%) or father, 38 (27.3%).
      Disclosure to an unmarried sexual partner was low as only six (12.0%) of the 50
      single youth who had a current sexual partner had disclosed their status to
      him/her. Youth who were aware that their spouse/partner was HIV positive (OR =
      9.87; CI = 1.09-88.83) or negative (OR = 9.98; CI = 1.18-84.70) were more likely
      to have disclosed their status than those unaware of their spouse/partners'
      status. Disclosure was also higher among members of an HIV support group (OR =
      3.32; CI = 1.03-10.72). Conclusions Many respondents had disclosed their status
      although disclosure to an unmarried sexual partner was low. Interventions to
      improve HIV disclosure especially among unmarried sexually active youth could
      improve disclosure and overall management of HIV in our study area.

PMID- 29332012
TI  - Classical (adiponectin, leptin, resistin) and new (chemerin, vaspin, omentin)
      adipocytokines in patients with prediabetes.
AB  - Background In the last decade, there has been an increased interest toward fat
      tissue as an endocrine organ that secretes many cytokines and bioactive mediators
      that play a role in insulin sensitivity, inflammation, coagulation and the
      pathogenesis of atherosclerosis. The aim of this study was to investigate
      classical (adiponectin, leptin, resistin) and new (chemerin, vaspin, omentin)
      adipocytokine levels in subjects with prediabetes [impaired fasting glucose (IFG)
      and/or impaired glucose tolerance (IGT)] and obese subjects with normoglycemia.
      Methods In this study, 80 patients with a mean age of 50.4 +/- 10.6 years were
      recruited, divided into two groups with similar age and body mass index (BMI) -
      with obesity and normoglycemia (n = 41) and with obesity and prediabetes (n =
      39). Results Serum adiponectin levels were significantly higher in subjects with
      normoglycemia compared to patients with prediabetes. Adiponectin has a good
      discriminating power to distinguish between patients with and without insulin
      resistance in our study population [area under the curve (AUC) = 0.728, p =
      0.002]. Other adipocytokine levels were not significantly different between the
      two groups. The patients with metabolic syndrome (MetS) had significantly lower
      levels of leptin compared to those without MetS (33.03 +/- 14.94 vs. 40.24 +/-
      12.23 ng/mL) and this difference persisted after adjustment for weight and BMI.
      Receiver operating characteristic (ROC) analysis showed that low serum leptin can
      predict the presence of MetS (p = 0.03), AUC = 0.645. Conclusion Serum
      adiponectin is statistically higher in patients with normoglycemia compared to
      those with prediabetes and has a predictive value for distinguishing between
      patients with and without insulin resistance in the studied population. Serum
      leptin has a good predictive value for distinguishing between patients with and
      without MetS in the studied population.

PMID- 29332014
TI  - Influence of waist circumference on blood pressure status in non-obese
      adolescents.
AB  - Objectives To check whether excess in abdominal adiposity and metabolic factors
      were associated with blood pressure abnormalities in non-obese adolescents.
      Methods We randomly selected 1100 adolescent students, aged 12-18 years, from
      schools and classrooms in the city of Constantine, Algeria. Among them 179 were
      overweight and 51 were obese (IOTF criteria). Waist circumference (WC) was
      considered high if >74 cm in boys and 75 cm in girls (mean of WC of all
      population studied). Hypertension (HBP) and prehypertension (preHBP) were defined
      by the NHBPEP's 2004 criteria. Results The prevalence of HBP/preHBP were
      13.0%/12.4% with no difference between boys and girls. The percentages of
      HBP/preHBP patients were 15.6%/15.6% in overweight adolescents, 5.9%/31.4% in
      obese adolescents and 12.9%/10.6% in adolescents with normal body weight (p <
      0.0001). In obese adolescents, the prevalence of HBP was higher among boys than
      girls (36% vs. 27%, p = 0.002). In normal and overweight adolescents, the
      prevalence of HBP and preHBP was similar in boys and girls (11.9% vs. 11.0% and
      14.7% vs. 12.1%); the association of WC (high vs. not high) with HBP was found in
      boys (16.1% vs. 8.8%, p = 0.009) but not in girls (12.1% vs. 10.2%), and with
      preHBP in girls (15.5% vs. 8.0%, p = 0.029) but not in boys (16.2% vs. 13.6%).
      Waist circumference [OR: 1.04 (1.03-1.06); p < 0.0001] and HOMA index [OR: 1.65
      (1.13-2.39); p = 0.009] were associated with an increased risk of HBP. Conclusion
      In non-obese adolescents, a high WC, defined by values over the mean WC observed
      in our population, is associated with a higher risk of HBP in boys.

PMID- 29332015
TI  - Post-traumatic stress and growth among CPR survivors in the southeast of Iran.
AB  - Background Almost 7.2%-10.6% of patients survive CPR in Iran. Most of them
      experience post-traumatic stress disorder (PTSD) and post-traumatic growth (PTG).
      There are limited studies to assessing the correlation between these two
      psychological outcomes among CPR survivors. Objective This study aimed to examine
      the correlation between PTSD and PTG among CPR survivors in South-East Iran.
      Subjects Using Quota sampling, 163 CPR survivors in two provinces in the South
      East of Iran were selected to participate in this study. Method A descriptive
      correlational study was used to fulfill the aim of the study. The impact of Event
      Scale-Revised (IES-R) for assessing PTSD and Post-traumatic growth questionnaires
      were used to assess PTG. Results The mean score of PTSD was 39.89 and according
      to the cutoff point, 87.1% of participants suffered from PTSD. The mean score of
      PTG was 78.6. PTSD and PTG had significant negative correlation. The result of
      multi-variate logistic regression showed that only the PTG score predicted PTSD
      (Odds ratio = 0.79, CI = 0.72-0.87; and p < 0.001). The result of multi-variate
      linear regression indicated that PTSD, time passed since CPR, and physical
      disability caused by CPR predicted PTG score significantly. Conclusion This study
      provides CPR survivors and health care personnel with some valuable insights
      about cultural aspects of PTSD and PTG among CPR survivors and that PTG is
      positively influenced by physical disability and time passed since CPR. CPR
      survivors may gain positive experience and valuable insight in group meetings and
      discussions with their counterparts.

PMID- 29332016
TI  - Tribute to a giant: Emanuel Chigier, MD, 1928-2017.

PMID- 29332017
TI  - Insulin resistance and lung function in obese asthmatic pre-pubertal children.
AB  - BACKGROUND: Recent findings have supposed that the underlying association between
      the increased prevalence of both asthma and obesity may be insulin resistance
      (IR). METHODS: Insulin and glucose serum levels were analyzed to calculate the
      homeostatic model assessment of insulin resistance (HOMA-IR) for IR in 98 pre
      pubertal children. Lung function and allergy status evaluation were performed.
      The study population was divided into four groups: (1) obese asthmatic children
      (ObA); (2) normal-weight asthmatic children (NwA); (3) normal-weight non
      asthmatic children (Nw) and (4) obese non-asthmatic children (Ob). RESULTS:
      Forced expiratory volume in 1 s (FEV1) was slightly lower in obese subjects
      compared with normal-weight subjects and forced vital capacity (FVC) appeared
      lower in asthmatics, whereas between non-asthmatics subjects, it was lower in the
      obese group than in the normal-weight one. The post hoc analysis revealed a
      statistically significant reduction in FEV1, peak expiratory flow (PEF), forced
      expiratory flows (FEF) between 50% and 25% of the FVC (FEF50 and FEF25) between
      ObA and Nw and in FEV1, FVC, PEF, FEF50 and FEF25 between NwA and Nw, but no
      statistically significant differences of lung function parameters were observed
      between ObA and NwA. We found an inverse relationship between HOMA-IR and all
      spirometric parameters, although without any statistical significance. We also
      observed a significantly lower FVC in insulin-resistant children (HOMA-IR>95th
      percentile) (p=0.03). CONCLUSIONS: This study suggests that lung function could
      be early altered in obese children, already in pre-pubertal age. Although IR
      should not manifest its effects on lungs in pre-pubertal obese children, the
      prevention or treatment of obesity in the pre-pubertal period may prevent
      definitive negative effects on lungs.

PMID- 29332018
TI  - The Epidemic of Obesity.
AB  - No Abstract Available.

PMID- 29332019
TI  - A Review of the Evolution of Ayurveda in the United States.
AB  - No Abstract Available.

PMID- 29332021
TI  - The Effects of Reflexology on Fatigue and Anxiety in Patients With Multiple
      Sclerosis.
AB  - Context * Multiple sclerosis (MS) is an inflammatory, demyelinating disease of
      the central nervous system. In addition to the progressive nature of the disease,
      devastating symptoms adversely affect the patient's daily life and future
      expectations. This situation leads patients to seek complementary and alternative
      treatments. Objectives * This study was conducted to determine the effects of
      reflexology on fatigue severity and anxiety in patients with MS. Design * The
      research was a quasi-experimental, pretest-posttest design. Setting * The
      research was conducted at the Mavi Isiklar Rehabilitation Center of the
      Metropolitan Municipality of Samsun (Samsun, Turkey), in cooperation with the
      Faculty of Medicine's Hospital Neurology Clinic and the Health Application and
      Research Center at Ondokuz Mayis University (Samsun, Turkey), and with the Black
      Sea MS Association. Participants * Participants were patients who participated in
      the MS Patient School program at the center and who had been diagnosed with MS at
      least 1 y prior to the start of the study. Inventions * Reflexology was applied
      for 60 min, 30 min for each leg. Reflexology was conducted in an ergonomic and
      positionable bed in a special physiotherapy room within the Mavi Isiklar resting
      facilities. Outcome Measures * Sociodemographic data forms, a fatigue severity
      scale (FSS), and a state-trait anxiety inventory (STAI) were used in the data
      collection. Results * Fifteen patients participated in the study. The average age
      of the participants was determined to be 39.20 +/- 11.89 y. Before the
      participants received reflexology, the average FSS score was 40.06 +/- 19.27; the
      mean (+/-SD) STAI-S score was 50.33 +/- 9.48; and the mean (+/-SD) STAI-T score
      was 43.33 +/- 9.48. The average FSS score after reflexology was 27.66 +/- 21.23;
      the mean (+/-SD) STAI-S score was 37.53 +/- 10.11; and the mean (+/-SD) STAI-T
      score was 31.86 +/- 10.27. Conclusions * The study indicates that reflexology can
      be an effective method for reducing fatigue severity and anxiety in patients with
      MS.

PMID- 29332022
TI  - Comparative Antitussive Effects of Medicinal Plants and Their Constituents.
AB  - Context * The cough is a protective reflex, with 2 types, one being more
      sensitive to mechanical stimulation and the other to chemical stimulation, such
      as sulfur dioxide, ammonia, citric acid, and capsaicin. Some evidence is
      available that suppressant therapy is most effective when used for the short-term
      reduction of coughing. Today, use of herbal drugs is increasing all over the
      world for various ailments, including to provide antitussive activity. Objective
      * The study intended to review the antitussive effects of various extracts, some
      fractions, and some constituents of the studied medicinal plants. Design *
      Various databases, including the Medline, Science Direct, Scopus, and Google
      Scholar, were searched for studies published between 1978 and 2015, using the
      keywords antitussive and cough and the names of various medicinal plants and
      their constituents. Setting * The study took place in the districts related to
      Mashhad University of Medical Sciences (Mashhad, Iran). Outcome Measures * The
      antitussive effects of medicinal plants and their constituents were normalized to
      50 mg/kg and 1 mg/mL against various cough stimulants and compared. Results * The
      most potent antitussive effect was observed for Nigella sativa and Linum
      usitatissimum on coughs induced by sulfur dioxide. Artemisia absinthium showed a
      higher antitussive effect on cough induced by ammonia compared with the other
      studied medicinal plants. The antitussive effects of Cuminum cyminum and
      Glycyrrhiza glabra were more potent on cough induced by citric acid than other
      medicinal plants. Conclusions * These results suggest the therapeutic potential
      of the studied medicinal plants as antitussive therapies. However, only a few
      clinical studies have examined the antitussive effects of medicinal plants, and
      more clinical studies are needed. The underlying mechanisms of the antitussive
      effects of medicinal plants should be also examined in further studies.

PMID- 29332020
TI  - Predictors of Improvements in Mental Health From Mindfulness Meditation in
      Stressed Older Adults.
AB  - Context * The benefits of a mindfulness meditation (MM) intervention are most
      often evidenced by improvements in self-rated stress and mental health. Given the
      physiological complexity of the psychological stress system, it is likely that
      some people benefit significantly, whereas others do not. Clinicians and
      researchers could benefit from further exploration to determine which baseline
      factors can predict clinically significant improvements from MM. Objectives * The
      study intended to determine (1) whether the baseline measures for participants
      who significantly benefitted from MM training were different from the baseline
      measures of participants who did not, and (2) whether a classification analysis
      using a decision-tree, machine-learning approach could be useful in predicting
      which individuals would be most likely to improve. Design * The research team
      performed a secondary analysis of a previously completed randomized, controlled
      clinical trial. Setting * The study occurred at the Oregon Health & Science
      University (Portland, OR, USA) and in participants' homes. Participants *
      Participants were 134 stressed, generally healthy adults from the metropolitan
      area of Portland, Oregon, who were 50 to 85 y old. Intervention * Participants
      were randomly assigned either to a 6-wk MM intervention group or to a waitlist
      control group, who received the same MM intervention after the waitlist period.
      Outcome Measures * Outcome measures were assessed at baseline and at 2-mo follow
      up intervals. A responder was defined as someone who demonstrated a moderate,
      clinically significant improvement on the mental health component (MHC) of the
      short-form health-related quality of life (SF-36) (ie, a change >=4). The MHC had
      demonstrated the greatest effect size in the primary analysis of the previously
      mentioned randomized, controlled clinical trial. Potential predictors were
      demographic information and baseline measures related to stress and affect.
      Univariate statistical analyses were performed to compare the values of
      predictors in the responder and nonresponder groups. In addition, predictors were
      chosen for a classification analysis using a decision tree approach. Results * Of
      the 134 original participants, 121 completed the MM intervention. As defined
      previously, 61 were responders and 60 were nonresponders. Analyses of the
      baseline measures demonstrated significant differences between the 2 groups in
      several measures: (1) the positive and negative affect schedule negative subscale
      (PANAS-neg), (2) the SF-36-MHC, and (3) the SF-36 energy/fatigue, with clinically
      worse scores being associated with greater likelihood of being a responder.
      Disappointingly, the decision-tree analyses were unable to achieve a
      classification rate of better than 65%. Conclusions * The differences in
      predictor variables between responders and nonresponders to an MM intervention
      suggested that those with worse mental health at baseline were more likely to
      improve. Decision-tree analysis was unable to usefully predict who would respond
      to the intervention.

PMID- 29332023
TI  - Autonomic Response Testing Compared With Immunoglobulin E Allergy Panel Test
      Results: Preliminary Report.
AB  - Context * Chronically ill patients who have failed standard medical assessment
      and therapies are often assessed by integrative medical providers for atypical
      manifestations of allergies as the possible source or contributing factor(s) to
      their condition. Skin testing and immunoglobulin E (IgE) allergy panels increase
      the cost of care in these patients. Objective * The objective of this study was
      to determine the accuracy of autonomic response testing (ART) as compared with
      IgE allergy panel blood tests. Design * This study was a retrospective chart
      review of patients who had ART and blood drawn for an IgE allergy panel at the
      same office visit. Outcome Measures * Sensitivity, specificity, positive
      predictive value, negative predictive value, overall accuracy, phi coefficient,
      and Cohen's kappa were calculated. Results * A total of 14 charts were reviewed.
      All measures of accuracy were of either useful or excellent strength. The
      strength of association measures of the phi coefficient and Cohen's kappa were
      strong. Conclusion * This first and preliminary evaluation of the allergy
      assessment utility of ART is very promising and reveals the need for more
      vigorous follow-up studies.

PMID- 29332024
TI  - The Effects of Apotel and Remifentanil on Postoperative Pain.
AB  - Context * One of the most common complications of a Caesarean section (C-section)
      is postoperative inflammation as well as operative and postoperative pain
      associated with the surgery. The control and mitigation of pain after surgery is
      the main goal of anesthesiologists. Objectives * This study aimed to compare the
      effects of intravenous apotel and remifentanil on postoperative pain control in
      women undergoing an elective C-section. Design * The research team designed a
      single-blinded, randomized clinical trial. Setting * The study was performed at
      the Taleghani Hospital (Arak, Iran). Participants * Potential participants were
      70 patients undergoing an elective C-section. Intervention * Participants were
      divided randomly into 2 groups, the apotel (A) and remifentanil (R) groups, with
      35 participants in each group. The participants in the A group received an
      infusion of 1 g of apotel to 200 cc of normal saline for 20 min, after
      anesthesia, the removal of their fetuses, and the clamping of their umbilical
      cords. The same procedure was followed for the R group (ie, the participants
      received an infusion of 0.5 MUg of remifentanil per kg of body weight per minute
      after anesthesia), removal of their fetuses, and clamping of their umbilical
      cords. Outcome Measures * Pain scores were measured 3 times using a visual
      analogue scale during the recovery period (from anesthesia and pain scores) and
      at 4 and 12 h after surgery after surgery. Participants' use of narcotics during
      the 24 h after surgery was recorded. Data analysis was done using SPSS (version
      16) statistical software. Results * The pain scores of the R group were lower
      than those of the A group during the recovery period and a statistically
      significant difference existed between the pain scores of the 2 groups during
      that period (P = .01). No statistically significant difference existed between
      the groups in participants' mean use of narcotic drugs during the 24 h of
      surgery. Moreover, no statistically significant differences were found between
      the groups in participants' blood pressures or heart rates during the recovery
      period or at 4 and 12 h after surgery (P >= .05). Conclusion * Remifentanil can
      provide better postoperative pain control than apotel immediately after surgery.

PMID- 29332025
TI  - Prolegomena to a True Integrative Medical Paradigm.
AB  - When a paradigm starts to show signs of failure to cope with significant
      questions in any basic/applied branch of human knowledge, there come on the scene
      those who have perused the related literature enough to either answer those major
      questions according to the established paradigm or proffer a (wholly) new way of
      looking at things. In the latter case, the history of science tells us, a
      paradigm shift takes place. Modern medicine cannot be proven to be totally
      disconnected from its traditional roots. Where traditional medicine came to give
      its place to present-day conventional medicine, a number of humanistic aspects of
      healing, in addition to some axioms of old wisdom, were actually lost. Employing
      a personalized strategy by considering the patient's specific conditions,
      integrative medicine endeavors to apply all appropriate interventions from a
      whole set of science branches to bring back health. However, this does not remain
      fully without its own challenges from almost all sides. Complementary and
      alternative medicine, on the one hand, and evidence-based medicine, on the other,
      have their own rightful say in the affair. Delving deep into the details of
      medical history's ups and downs, and examining-from the philosophy of medicine's
      and philosophy of science's standpoints-the pros and cons of integrative
      medicine, this present treatise makes a systemic, interdisciplinary effort to put
      forward the best possible paradigmatology in a methodical way as far as the
      demands of society are concerned.

PMID- 29332026
TI  - Medicinal Plant Materials in the Treatment of Anxiety Disorders: Neurobiological
      Aspects.
AB  - Context * Pathological anxiety, which affects approximately one-third of the
      world population, is an inadequate, irrational reaction of an organism to the
      environment and to a potential threat. Despite advancements in pharmacotherapy
      for anxiety disorders, further studies are still necessary to search for new
      substances possessing the desired anxiolytic effects, with as few unwanted
      effects as possible. Objective * This study intended to examine the
      characteristics of medicinal plant materials that exhibit anxiolytic properties,
      with a special emphasis on the mechanisms of action of their active ingredients
      on the systems involved in the pathophysiology of anxiety. Design * The research
      team performed a review of the literature, searching well-known online scientific
      databases, including PubMed, Google Scholar, Medline, ScienceDirect, and
      SpringerLink. The team searched for the newest research from various regions of
      the world. Setting * The study was done in the Medical University of Silesia
      (Katowice, Poland). Results * The medicinal plant materials presented in the
      current article undoubtedly influence the central nervous system. Our analysis
      showed that their mechanism of action is very complicated and appropriately still
      enigmatic. Among them, V officinalis represents the most thoroughly investigated
      medicinal plant material that produces anxiolytic, sedative effects. However,
      extracts of other medicinal plants may also emerge as helpful in the treatment of
      fear and anxiety and in the prophylaxis of those disorders. Conclusions * The
      current review discusses the most recent data on medicinal plant materials that
      are effective as anxiolytic treatments, with special emphasis on the
      neurobiological mechanisms of action of their active ingredients. The research
      team hopes that the information may open up new directions in the search for
      drugs capable of enhancing the existing therapy.

PMID- 29332027
TI  - Phyllodes tumors of the breast: clinicopathological analysis of 106 cases from a
      single institution.
AB  - BACKGROUND: Phyllodes tumors (PT) are uncommon biphasic tumors, accounting for
      less than 1% of all breast primary neoplasms. They form a wide variety of tumors
      ranging from benign to malignant. Several histological features are used to grade
      PT into 3 categories: benign (grade I), borderline (grade II) and malignant
      (grade III) tumors. The aim of our study was to analyse histolopathological,
      radiological and clinical features of PT from an experience of a single center.
      METHODS: It was a retrospective study including 106 patients diagnosed with
      phyllodes tumors on surgical specimens at the department of pathology, of Hassan
      II university hospital (Fez, Morocco), from 2009 to 2016. RESULTS: The mean age
      was 33.81 years (range of 13-66 years), and the mean age increases with the tumor
      grade (mean ages of 32.32, 32.87 and 33.65 years respectively for grade I, II and
      III PT) (p = 0.023); 78 patients (73.58%) had benign PT, 20 (18.86%) had
      borderline PT and 8 (7.54%) patients were diagnosed with malignant PT. Mostly,
      the tumor size was <5 cm (63.2%), with BI-RADS 3 (51 patients, 48.11%). The tumor
      size and the radiological suspicion (ACR/BI-RADS) increased with the tumor grade
      (p < 0.001). Mitosis count, cellular atypia and stromal cellularity increased
      with the tumor grade (p < 0.001). Also, the presence of necrosis is associated
      with malignant PT (p < 0.001). Before surgery, patients had undergone core needle
      biopsies (CNB) for diagnostic purpose, and the overral sensitivity of this
      diagnostic procedure was 71.83%. The sentivity of the CNB decreased from grade I
      PT to grade III PT (from 56.81% to 37.5%), however its specificity increased from
      grade I to grade III PT (from 59.25% to 100%). CONCLUSION: Phyllodes tumors of
      the breast are rare neoplasms with a wide range of clinicopathologic
      presentations. The core needle biopsy has a good diagnostic sensitivity compared
      to definitive diagnosis on surgical specimens. There was a statistically
      significant association between the histological grade of PT and tumor size,
      radiological suspicion, mitotic count, cellular atypia, stromal cellularity, and
      tumor necrosis.

PMID- 29332028
TI  - Possible erythrocyte contributions to and exacerbation of the post-thrombolytic
      no-reflow phenomenon.
AB  - BACKGROUND: Reperfusion injury often occurs with therapeutic intervention
      addressing the arterial occlusions causing acute myocardial infarction and
      stroke. The no-reflow phenomenon has been ascribed to leukocyte plugging and
      blood vessel constriction in the microcirculation. OBJECTIVE: To assess possible
      red cell contributions to post-thrombolytic no-reflow phenomenon. METHODS: Blood
      clots were formed by recalcifying 1 ml of citrated fresh human venous blood and
      then lysed by adding 1,000 units of streptokinase (SK) at several intervals
      within 1 hour. Red cell deformability was tested by both a microscopic
      photometric and a filtration technique, viscosity by a cone and plate viscometer,
      and erythrocyte aggregation by an optical aggregometer. RESULTS: Two sampling
      methods were devised for the microscopic photometric test, both of which
      indicated increases of erythrocyte stiffness after being lysed from the clot by
      SK. In accompanying experiments, the viscosity, aggregation and filterability of
      the post-lytic erythrocytes were assessed. Results indicated increased viscosity
      in Ringer's, decreased aggregation index and filterability through a 5 MUm pore
      size Nuclepore membrane. CONCLUSION: Findings demonstrated that post-lytic
      changes in red cell deformability do occur which could contribute to the no
      reflow phenomenon.

PMID- 29332029
TI  - Biomechanical effects of USS fixation with different screw insertion depths on
      the vertebrae stiffness and screw stress for the treatment of the L1 fracture.
AB  - OBJECTIVE: To evaluate the biomechanical effects of internal fixation with
      different screw insertion depths on vertebrae stiffness and screw stress for L1
      fracture. METHODS: The established L1 fracture was fixed with 10 different depths
      of screw insertion: 10-100% screw-path length (SPL). Loading on the T12 endplate
      was simulated. RESULTS: Screws inserted to 60-100% depths has a higher axial
      displacement of screw against injured vertebrae and maximum stress of screws
      compared to those of screws inserted to 30-50% depths and 10-20% (P< 0.05). No
      significant difference was noted among 60-100% SPL groups. Under single loading
      condition, the incidence rate of maximum stress of each screw ranged from 16.7
      50.0%. Chi-square test showed superior screw has a higher incidence rate of
      maximum stress than inferior screw (P< 0.05). CONCLUSIONS: Screws inserted to 60%
      depth or more can achieve effective strength to withstand the postoperative
      height correction loss of the L1 vertebrae fracture. However, continuous
      prolonged depth of screw insertion did not significantly increase the effective
      strength of the screw against injured vertebrae and maximum equivalent stress of
      screws. The incidence rate of the maximum stress of each screw in correlated with
      position of screw insertion but not associated with the screw insertion depth.

PMID- 29332030
TI  - What is a more effective method of cranio-cervical flexion exercises?
AB  - BACKGROUND: Cranio-cervical flexion exercise (CCFE) is a representative exercise
      that activates the deep muscles of neck pain patients. However, there is a lack
      of studies that propose specific exercise methods to examine the more effective
      activity level of the deep cervical flexor. OBJECTIVE: The objective of this
      study is to propose a more effective exercise method through effect comparison
      based on an optimal degree of mouth-opening, a mouth-open versus mouth-closed
      position, eye gaze, and body position change during CCFE. METHODS: As a result of
      examining the optimal degree of mouth-opening during CCFE using a pressure
      biofeedback unit with 50 subjects conforming to a selection standard,
      sternocleidomastoid muscle activity was examined. An optimal degree of mouth
      opening during CCFE was examined as well. In addition, muscle thickness and
      muscle activity were measured based on eye gaze. Then, the effect of the exercise
      based on body position was examined. RESULTS: The lowest sternocleidomastoid
      activity was presented at a mouth-opening of 20 mm. A significant difference was
      presented in sternocleidomastoid and longus colli muscle activity at a mouth
      opening of (p< 0.05). The eye gaze of 45? below presented the lowest
      sternocleidomastoid activity. CONCLUSIONS: The results suggest a new type of
      exercise method with the accompaniment of an optimal degree of mouth-opening of
      (20 mm), along with an eye gaze of 45? below, and an exercise method in the
      seated position without spatial restriction in order to increase the effect of
      CCFE, one of the conventional neck stabilization exercise methods.

PMID- 29332031
TI  - Difference of the thickness and activation of trunk muscles during static stoop
      lift at different loads between subjects with and without low back pain.
AB  - BACKGROUND: Patients suffering from low back pain (LBP) have been reported to
      alter muscle contraction strategies. OBJECTIVE: To compare activity and thickness
      of the trunk muscles (external oblique (EO), internal oblique (IO), transversus
      abdominis (TrA), and lumbar multifidus (LM)) during static stoop lift at
      different lifting loads between the subjects with and without LBP. METHODS:
      Twenty eight subjects with LBP and twenty eight healthy subjects were recruited.
      The stoop lifting was performed in three conditions in 0%, 10%, and 20% of body
      weight. RESULTS: The activity of EO (F= 9.513) and IO (F= 7.781) was
      significantly increased with increasing lifting loads in subjects with LBP (p<
      0.05) but not significantly in subjects without LBP. The activity of the LM (F=
      124.980) was significantly increased in response to lifting loads in both groups
      (p< 0.05). The percent change of TrA (F= 8.797) and LM (F= 48.170) muscles
      thickness was significantly increased with increasing lifting loads in both
      groups (p< 0.05). The percent change of TrA (F= 3.780) and LM (F= 16.314) muscles
      thickness in subjects without LBP was greater than those in subjects with LBP at
      all three lifting loads (p< 0.05). CONCLUSIONS: The results of this study suggest
      that more activation of EO in subjects with LBP may contribute to increase the
      compressive force on the lumbar spine during stoop lift. Also, less activation of
      TrA and LM in subjects with LBP may contribute to decrease the lumbar
      stabilization during stoop lift.

PMID- 29332032
TI  - Value of conventional MRI and diffusion tensor imaging parameters in predicting
      surgical outcome in patients with degenerative cervical myelopathy.
AB  - BACKGROUND: In addition to conventional magnetic resonance imaging (cMRI),
      diffusion tensor imaging (DTI) has been investigated as a potential diagnostic
      and prognostic tool for patients with degenerative cervical myelopathy (DCM).
      OBJECTIVE: To assess the efficacy of cMRI and DTI parameters in prediction of
      surgical outcome in DCM patients. METHODS: One hundred and forty-two patients
      with DCM who underwent presurgical cMRI and DTI of the cervical spine were
      included. Quantitative parameters obtained by cMRI included compression ratio
      (CR), transverse area (TA), and signal intensity ratio (SIR). DTI was evaluated
      for apparent diffusion coefficient (ADC) and fractional anisotropy (FA). The
      Japanese Orthopaedic Association (JOA) score and recovery rate were used to
      evaluate clinical outcomes. A JOA recovery rate < 50% was defined as a poor
      surgical outcome. The relationship of surgical outcome with various imaging
      parameters was examined. Receiver operating characteristic (ROC) curves were used
      to measure the predictive ability and determine the best cut-off values of the
      quantitative parameters. RESULTS: By ROC curve analyses of imaging parameters,
      the largest area under the ROC curve (AUC) was for FA (0.750), followed by ADC
      (0.719), TA (0.716), SIR (0.673), and CR (0.591). The cut-off values with the
      best compromise between sensitivity and specificity were set at 0.390 for FA,
      1.344 * 10-3 mm2/s for ADC, 46.02 mm2 for TA, 1.556 for SIR, and 26.56% for CR.
      Multivariate logistic regression model revealed that JOA score ? 8 points, TA ?
      46.02 mm2, and FA ? 0.390 were independently associated with poor surgical
      outcome. The AUC value for the three-predictor model was 0.871, indicating strong
      predictive discrimination, and was significantly higher than the AUC value for
      the model containing only the JOA score (0.763; P= 0.003). CONCLUSIONS: JOA score
      is a reasonable predictor of surgical outcome in DCM. However, a model inclusive
      of TA and FA provides superior predictive ability. Thus, quantitative analysis of
      cMRI and DTI is useful for predicting surgical outcome in DCM.

PMID- 29332033
TI  - Effect of dual tasking on anticipatory and compensatory postural adjustments in
      response to external perturbations in individuals with nonspecific chronic low
      back pain: Electromyographic analysis.
AB  - BACKGROUND: In patients with chronic low back pain (CLBP), postural control is a
      demanding task in terms of attention. Although the attentional demands of
      postural control have been investigated in these patients, the attentional
      demands of postural recovery during dual task performance have not been evaluated
      in patients with nonspecific CLBP. OBJECTIVE: To investigate the effect of dual
      tasking on anticipatory and compensatory postural adjustments in response to an
      external perturbation in patients with nonspecific CLBP. METHODS: Twenty-five
      patients with nonspecific CLBP of at least 3 months' duration and 25 healthy
      persons were exposed to predictable and unpredictable external perturbations. The
      attentional demands of postural adjustments were evaluated while participants
      simultaneously performed a cognitive task. Onset latency and integrated
      electromyographic activity of the trunk and leg muscles were compared between
      dual task (postural recovery and backward digit span memory) and single task
      conditions (postural recovery only). RESULTS: The results showed delayed
      activation of the tibialis anterior (agonist) and early activation of the
      gastrocnemius (antagonist) muscles during the dual task in patients with
      nonspecific CLBP compared to healthy participants. Integrated electromyographic
      activity was significantly greater in the dual task than the single task
      condition in the gastrocnemius (antagonist) muscle in patients with nonspecific
      CLBP compared to healthy persons during unpredictable perturbations. CONCLUSION:
      The impaired ankle muscle activities during a cognitive task suggest that
      postural control recovery following external perturbation requires attentional
      resources in patients with nonspecific CLBP. This may increase the risk of re
      injury in people with nonspecific CLBP while they perform an attentionally
      demanding task in more difficult circumstances.

PMID- 29332034
TI  - Microhemodynamic indices to evaluate the effectiveness of herbal medicine in
      diabetes: A comparison between alpha-mangostin and curcumin in the retina of type
      2 diabetic rats.
AB  - OBJECTIVE: This study was aimed to develop microhemodynamic indices to evaluate
      the effectiveness of herbal medicine in diabetic tissues. METHODS: Male Sprague
      Dawley rats were divided into four groups: normal control rats (Control), type 2
      diabetic rats without (DM2) and with supplementation of alpha mangostin (DM2-MG)
      or curcumin (DM2-CUR). Alpha-mangostin or curcumin (200 mg/kg BW) were fed
      followed by i.p. injection of streptozotocin (STZ). Mean arterial pressure (MAP)
      and retinal blood flow (RBF) were measured and retinal flow resistance (RFR) was
      calculated. Three indices were developed to evaluate the effectiveness of herbal
      medicines in RFR-MAP diagram based on experimental data of MAP and RFR in type 2
      diabetic rats. These indices are alpha, beta, and gamma where alpha is a ratio of
      reduction in MAP, beta is a ratio of reduction in RFR increasing with MAP
      increase, and gamma indicates a ratio of reduction in RFR. RESULTS: The elevated
      MAP and RFR and decreased RBF were observed in DM2 rats.Interestingly, alpha
      mangostin or curcumin supplementation significantly increased RBF while decreased
      MAP and RFR. Using alpha, beta and gamma indices, it was found that alpha
      mangostin is more effective than curcumin in type 2 diabetic retina. CONCLUSIONS:
      These microhemodynamic indices may be useful to compare various herbal medicines
      in different tissues.

PMID- 29332035
TI  - An Aspartyl Cathepsin Targeted PET Agent: Application in an Alzheimer's Disease
      Mouse Model.
AB  - BACKGROUND: Early detection of Alzheimer's disease (AD) pathology is a serious
      challenge for both diagnosis and clinical trials. The aspartyl protease,
      Cathepsin D (CatD), is overexpressed in AD and could be a biomarker of disease.
      We have previously designed a unique contrast agent (CA) for dual-optical and
      magnetic resonance imaging of the activity of the CatD class of enzymes.
      OBJECTIVE: To compare the uptake and retention of a novel, more sensitive, and
      clinically-translatable 68Ga PET tracer targeting CatD activity in 5XFAD mice and
      non-Tg littermates. METHODS: The targeted CA consisted of an HIV-1 Tat cell
      penetrating peptide (CPP) conjugated to a specialized cleavage sequence targeting
      aspartyl cathepsins and a DOTA conjugate chelating 68Ga. PET images were acquired
      using a Siemens Inveon preclinical microPET in female Tg AD mice and non-Tg age
      matched female littermates (n = 5-8) following intravenous CA administration at
      2, 6, and 9 months of age. Additionally, 18F fluorodeoxyglucose (FDG) PET imaging
      was performed at 10 months to measure glucose uptake. RESULTS: The Tg mice showed
      significantly higher relative uptake rate of the targeting CA in the forebrain
      relative to hindbrain at all ages compared to controls, consistent with
      histology. In contrast, no differences were seen in CA uptake in other organs.
      Additionally, the Tg mice did not show any differences in relative uptake of FDG
      at 10 months of age in the forebrain relative to the hindbrain compared to age
      matched non-Tg controls. CONCLUSIONS: Elevated aspartryl cathepsin activity was
      detected in vivo in the 5XFAD mouse model of AD using a novel targeted PET
      contrast agent.

PMID- 29332036
TI  - Relationships Between Lower Olfaction and Brain White Matter Lesions in Elderly
      Subjects with Mild Cognitive Impairment.
AB  - BACKGROUND: Olfactory impairment is reported in mild cognitive impairment (MCI)
      and Alzheimer's disease (AD) and is associated with hippocampal atrophy. In
      elderly people, dementia with AD neuropathology and white matter lesions (WML) is
      common. In this context, olfactory impairment could also depend on the presence
      of WML. OBJECTIVE: To assess the cross-sectional relationship between olfaction
      and WML in elderly subjects with MCI. METHODS: Consecutive subjects, >65 years
      old, diagnosed as MCI after a comprehensive neuropsychological assessment in an
      expert memory center, with a brain MRI performed within a year and without major
      depressive state, were included. Olfaction was assessed by the Brief Smell
      Identification Test (BSIT). Two trained neuroradiologists, blind to cognitive and
      olfaction status, visually assessed hippocampal atrophy according to Scheltens'
      scale and WML according to Fazekas criteria. RESULTS: Seventy-five MCI subjects
      (mean age (SD) = 77.1 (6.2) years, 74.7% of women) were included. After
      adjustment for age and sex, factors associated with low BSIT scores were older
      age (p = 0.007), lower BMI (p = 0.08), lower MMSE score (p = 0.05), lower FCRST
      (p = 0.008), hippocampal atrophy (p = 0.04), periventricular WML (p = 0.007), and
      deep WML burden (p = 0.005). In multivariate analysis, severe deep WML (OR (95%
      CI) = 6.29 (1.4-35.13), p = 0.02) remained associated with low BSIT score
      independently from hippocampal atrophy. CONCLUSION: In elderly MCI subjects, low
      olfactory performances are associated with WML, whose progression may be slowed
      by vascular treatments. A longitudinal study to evaluate whether the progression
      of WML, hippocampal atrophy and low olfactory function, can predict accurately
      conversion from MCI to dementia is ongoing.

PMID- 29332038
TI  - Sex Influences the Accuracy of Subjective Memory Complaint Reporting in Older
      Adults.
AB  - Subjective memory complaints (SMC) are required when diagnosing amnestic mild
      cognitive impairment (aMCI), although their relationship with objective memory
      performance and Alzheimer's disease (AD) pathology remains unclear. We
      investigated whether the sex of the patient/participant moderates these
      associations. Participants were 940 normal control (NC) and aMCI participants
      from the Alzheimer's Disease Neuroimaging Initiative. SMC were assessed via the
      memory scale of the Everyday Cognition questionnaire. Discrepancy scores were
      calculated between self- and informant-reports and categorized into
      "overestimates," "comparable estimates", and "underestimates" of SMC. We
      conducted linear and logistic regressions to examine the interaction of sex with
      self- and informant-reported SMC and discrepancy group on the Rey Auditory Verbal
      Learning Test (RAVLT) Immediate and Delayed Recall and on PET measures of amyloid
      beta (Abeta) positivity. Diagnosis-stratified analyses were also conducted.
      Overall, there were sex by self- and informant-reported SMC interactions for
      Immediate and Delayed Recall. Despite a higher proportion of "overestimates" in
      women, greater self- and informant-reported SMC showed a stronger relationship to
      poorer RAVLT scores in women versus men. Diagnosis-stratified analyses revealed
      that results were driven by aMCI participants. Conversely, overall, greater self-
      and informant-reported SMC related to greater odds of Abeta positivity regardless
      of sex. In diagnosis-stratified analyses, only informant-reported SMC related to
      Abeta positivity in aMCI. Relative to "comparable estimates," "underestimates" of
      SMC were associated with poorer RAVLT scores across sexes in the overall sample
      and in aMCI. The predictive utility of self-report SMC may be limited to women in
      aMCI. Sex differences should be considered when evaluating SMC.

PMID- 29332037
TI  - Increased Vulnerability of the Hippocampus in Transgenic Mice Overexpressing APP
      and Triple Repeat Tau.
AB  - Alzheimer's disease (AD) is the most common tauopathy, characterized by
      progressive accumulation of amyloid-beta (Abeta) and hyperphosphorylated tau.
      While pathology associated with the 4-repeat (4R) tau isoform is more abundant in
      corticobasal degeneration and progressive supranuclear palsy, both 3R and 4R tau
      isoforms accumulate in AD. Many studies have investigated interactions between
      Abeta and 4R tau in double transgenic mice, but few, if any, have examined the
      effects of Abeta with 3R tau. To examine this relationship, we crossed our APP751
      mutant line with our recently characterized 3R tau mutant model to create a
      bigenic line (hAPP-3RTau) to model AD neuropathology. Mice were analyzed at 3 and
      6 months of age for pathological and behavioral endpoints. While both the 3RTau
      and the hAPP-3RTau mice showed neuronal loss, increased tau aggregation, Abeta
      plaques and exhibited more behavioral deficits compared to the non-tg control,
      the bigenic mice often displaying relatively worsening levels. We found that even
      in young animals we found that the presence of APP/Abeta increased the
      accumulation of 3R tau in the neocortex and hippocampus. This observation was
      accompanied by activation of GSK3 and neurodegeneration in the neocortex and CA1
      region. These results suggest that in addition to 4R tau, APP/Abeta may also
      enhance accumulation of 3R tau, a process which may be directly relevant to
      pathogenic pathways in AD. Our results demonstrate that this bigenic model
      closely parallels the pathological course of AD and may serve as a valuable model
      for testing new pharmacological interventions.

PMID- 29332039
TI  - Alzheimer's Disease rs11767557 Variant Regulates EPHA1 Gene Expression
      Specifically in Human Whole Blood.
AB  - Large-scale genome-wide association studies have reported EPHA1 rs11767557
      variant to be associated with Alzheimer's disease (AD) risk in the European
      population. However, it is still unclear how this variant functionally
      contributes to the underlying disease pathogenesis. The rs11767557 variant is
      located approximately 3 kb upstream of EPHA1 gene. We think that rs11767557 may
      modify the expression of nearby genes such as EPHA1 and further cause AD risk.
      Until now, the potential association between rs11767557 and the expression of
      nearby genes has not been reported in previous studies. Here, we evaluate the
      potential expression association between rs11767557 and EPHA1 using multiple
      large-scale eQTLs datasets in human brain tissues and the whole blood. The
      results show that rs11767557 variant could significantly regulate EPHA1 gene
      expression specifically in human whole blood. These findings may further provide
      important supplementary information about the regulating mechanisms of rs11767557
      variant in AD risk.

PMID- 29332040
TI  - Synthetic Fragment of Receptor for Advanced Glycation End Products Prevents
      Memory Loss and Protects Brain Neurons in Olfactory Bulbectomized Mice.
AB  - Activation of receptor for advanced glycation end products (RAGE) plays an
      essential role in the development of Alzheimer's disease (AD). It is known that
      the soluble isoform of the receptor binds to ligands and prevents negative
      effects of the receptor activation. We proposed that peptide fragments from RAGE
      prevent negative effects of the receptor activation during AD neurodegeneration.
      We have synthesized peptide fragments from surface-exposed regions of RAGE.
      Peptides were intranasally administrated into olfactory bulbectomized (OBX) mice,
      which developed some characteristics similar to AD neurodegeneration. We have
      found that only insertion of fragment (60-76) prevents the memory of OBX mice.
      Immunization of OBX mice with peptides showed that again only (60-76) peptide
      protected the memory of animals. Both intranasal insertion and immunization
      decreased the amyloid-beta (Abeta) level in the brain. Activity of shortened
      fragments of (60-76) peptide was tested and showed only the (60-70) peptide is
      responsible for manifestation of activity. Intranasal administration of (60-76)
      peptide shows most protective effect on morpho-functional characteristics of
      neurons in the cortex and hippocampal areas. Using Flu-(60-76) peptide, we
      revealed its penetration in the brain of OBX mice as well as colocalization of
      Flu-labeled peptide with Abeta in the brain regions in transgenic mice. Flu-(60
      76) peptide complex with trimer of Abeta was detected by SDS-PAGE. These data
      indicate that Abeta can be one of the molecular target of (60-70) peptide. These
      findings provide a new peptide molecule for design of anti-AD drug and for
      investigation of RAGE activation ways in progression of AD neurodegeneration.

PMID- 29332041
TI  - In Vivo Visualization of Tau Accumulation, Microglial Activation, and Brain
      Atrophy in a Mouse Model of Tauopathy rTg4510.
AB  - BACKGROUND: Tau imaging using PET is a promising tool for the diagnosis and
      evaluation of tau-related neurodegenerative disorders, but the relationship among
      PET-detectable tau, neuroinflammation, and neurodegeneration is not yet fully
      understood. OBJECTIVE: We aimed to elucidate sequential changes in tau
      accumulation, neuroinflammation, and brain atrophy by PET and MRI in a tauopathy
      mouse model. METHODS: rTg4510 transgenic (tg) mice expressing P301L mutated tau
      and non-tg mice were examined with brain MRI and PET imaging (analyzed numbers:
      tg = 17, non-tg = 13; age 2.5~14 months). As PET probes, [11C]PBB3 (Pyridinyl
      Butadienyl-Benzothiazole 3) and [11C]AC-5216 were used to visualize tau pathology
      and 18-kDa translocator protein (TSPO) neuroinflammation. Tau pathology and
      microglia activation were subsequently analyzed by histochemistry. RESULTS: PET
      studies revealed age-dependent increases in [11C]PBB3 and [11C]AC-5216 signals,
      which were correlated with age-dependent volume reduction in the forebrain on
      MRI. However, the increase in [11C]PBB3 signals reached a plateau at age 7
      months, and therefore its significant correlation with [11C]AC-5216 disappeared
      after age 7 months. In contrast, [11C]AC-5216 showed a strong correlation with
      both age and volume reduction until age 14 months. Histochemical analyses
      confirmed the relevance of pathological tau accumulation and elevated TSPO
      immunoreactivity in putative microglia. CONCLUSION: Our results showed that tau
      accumulation is associated with neuroinflammation and brain atrophy in a
      tauopathy mouse model. The time-course of the [11C]PBB3- and TSPO-PET finding
      suggests that tau deposition triggers progressive neuroinflammation, and the
      sequential changes can be evaluated in vivo in mouse brains.

PMID- 29332043
TI  - Serum Non-Ceruloplasmin Non-Albumin Copper Elevation in Mild Cognitive Impairment
      and Dementia due to Alzheimer's Disease: A Case Control Study.
AB  - Several studies showed high serum copper levels in Alzheimer's disease (AD). The
      present study applied a newly developed method to detect serum copper free from
      proteins (free-Cu). Forty-four patients affected by dementia due to AD, thirty
      six patients affected by mild cognitive impairment (MCI) due to AD, and twenty
      eight healthy controls underwent clinical, cognitive, and MRI assessment. The new
      method showed higher free-Cu concentrations in MCI and dementia due to AD
      compared to controls (p < 0.0001). No correlation between copper levels,
      cognitive or MRI measures were found.

PMID- 29332044
TI  - Does the Genetic Feature of the Chinese Tree Shrew (Tupaia belangeri chinensis)
      Support Its Potential as a Viable Model for Alzheimer's Disease Research?
AB  - Alzheimer's disease (AD) is a neurodegenerative disease with increasing incidence
      across the world and no cure at the present time. An ideal animal model would
      facilitate the understanding of the pathogenesis of AD and discovery of potential
      therapeutic targets. The Chinese tree shrew (Tupaia belangeri chinensis) has a
      closer genetic affinity to primates relative to rodents, and can attain ages of 8
      years or older, which represents another advantage for the study of
      neurodegenerative diseases such as AD compared to primates. Here, we analyzed 131
      AD-related genes in the Chinese tree shrew brain tissues based on protein
      sequence identity, positive selection, mRNA, and protein expression by comparing
      with those of human, rhesus monkey, and mouse. In particular, we focused on the
      Abeta and neurofibrillary tangles formation pathways, which are crucial to AD
      pathogenesis. The Chinese tree shrew had a generally higher sequence identity
      with human than that of mouse versus human for the AD pathway genes. There was no
      apparent selection on the tree shrew lineage for the AD-related genes. Moreover,
      expression pattern of the Abeta and neurofibrillary tangle formation pathway
      genes in tree shrew brain tissues resembled that of human brain tissues, with a
      similar aging-dependent effect. Our results provided an essential genetic basis
      for future AD research using the tree shrew as a viable model.

PMID- 29332045
TI  - The Uniform Data Set, Czech Version: Normative Data in Older Adults from an
      International Perspective.
AB  - BACKGROUND: Outside of the United States, international perspectives on normative
      data for neuropsychological test performance, within diverse populations, have
      been scarce. The neuropsychological test battery from the Uniform Data Set (UDS)
      of the Alzheimer's Disease Centers (ADC) program of the United States National
      Institute on Aging (NIA) is one of the most sensitive batteries for the
      evaluation of both normal cognitive aging and pathological cognitive decline.
      OBJECTIVE: This study aimed to determine the feasibility of the Czech
      Neuropsychological Test Battery from the Uniform Data Set (UDS-Cz 2.0), while
      also evaluating the results obtained from an international perspective. METHODS:
      This paper describes data from 520 cognitively normal participants. Regression
      analyses were used to describe the influence of demographic variables on UDS-Cz
      test performance. RESULTS: Cognitive performance on all measures declined with
      age, with patient education level serving as a protective factor. Therefore, the
      present study provides normative data for the UDS-Cz, adjusted for the
      demographic variables of age and education. CONCLUSION: The present study
      determines the psychometric properties of the UDS-Cz and establishes normative
      values in the aging Czech population, which can be used in clinical settings.

PMID- 29332046
TI  - A Novel Antibody Targeting Tau Phosphorylated at Serine 235 Detects
      Neurofibrillary Tangles.
AB  - Alzheimer's disease is characterized by two main pathological hallmarks in the
      human brain: the extracellular deposition of amyloid-beta as plaques and the
      intracellular accumulation of the hyperphosphorylated protein tau as
      neurofibrillary tangles (NFTs). Phosphorylated tau (p-tau) specific-antibodies
      and silver staining have been used to reveal three morphological stages of NFT
      formation: pre-NFTs, intraneuronal NFTs (iNFTs), and extraneuronal NFTs (eNFTs).
      Here we characterize a novel monoclonal antibody, RN235, which is specific for
      tau phosphorylated at serine 235, and detects iNFTs and eNFTs in brain tissue,
      suggesting that phosphorylation at this site is indicative of late stage changes
      in tau.

PMID- 29332042
TI  - Protective Effects of Indian Spice Curcumin Against Amyloid-beta in Alzheimer's
      Disease.
AB  - The purpose of our article is to assess the current understanding of Indian
      spice, curcumin, against amyloid-beta (Abeta)-induced toxicity in Alzheimer's
      disease (AD) pathogenesis. Natural products, such as ginger, curcumin, and gingko
      biloba have been used as diets and dietary supplements to treat human diseases,
      including cancer, cardiovascular, respiratory, infectious, diabetes, obesity,
      metabolic syndromes, and neurological disorders. Products derived from plants are
      known to have protective effects, including anti-inflammatory, antioxidant, anti
      arthritis, pro-healing, and boosting memory cognitive functions. In the last
      decade, several groups have designed and synthesized curcumin and its derivatives
      and extensively tested using cell and mouse models of AD. Recent research on
      Abeta and curcumin has revealed that curcumin prevents Abeta aggregation and
      crosses the blood-brain barrier, reach brain cells, and protect neurons from
      various toxic insults of aging and Abeta in humans. Recent research has also
      reported that curcumin ameliorates cognitive decline and improves synaptic
      functions in mouse models of AD. Further, recent groups have initiated studies on
      elderly individuals and patients with AD and the outcome of these studies is
      currently being assessed. This article highlights the beneficial effects of
      curcumin on AD. This article also critically assesses the current limitations of
      curcumin's bioavailability and urgent need for new formulations to increase its
      brain levels to treat patients with AD.

PMID- 29332047
TI  - Sally-Anne Test in Patients with Alzheimer's Disease Dementia.
AB  - Social cognition has recently been recognized as one of the essential cognitive
      domains. Some reports suggested that patients with Alzheimer's disease dementia
      (ADD) presented significant theory of mind deficits even in the mild condition.
      However, most previous studies included only small numbers of patients with ADD.
      The present study administered the first-order false belief (Sally-Anne) test to
      116 consecutive patients with ADD from the outpatient units of the Memory Clinic
      and compared the characteristics of the two groups with correct and incorrect
      answers on the test. Then various clinical characteristics were evaluated. Only
      37.1% of patients with ADD correctly answered the Sally-Anne test with the right
      explanation. Comparison between the two groups of correct and incorrect answers
      revealed a significant association between the frontal assessment battery score
      and the result of the Sally-Anne test in the multiple logistic regression
      analyses. Thus, patients with ADD presented a significant deficit in social
      cognition even in the mild condition. Frontal dysfunction was thought to be
      related to the deficits in mild ADD.

PMID- 29332048
TI  - Frequency of Cardiovascular Genetic Risk Factors in a Calabrian Population and
      Their Effects on Dementia.
AB  - BACKGROUND: Several genetic variants playing a key role in cholesterol levels,
      blood pressure, and vascular dysfunction influence the risk of Alzheimer's
      disease (AD) and vascular dementia (VaD). The many meta-analysis studies carried
      out on large numbers of samples in different populations have not provided clear
      results to date, because a trans-ethnic shift of risk genotypes in different
      populations is often observed. OBJECTIVES: To determine genotypes allele
      frequencies of the polymorphisms most frequently identified to be correlated with
      cardio-cerebrovascular disease and AD in a Southern Italy population and to
      investigate their possible association with dementia. METHODS: The genotype and
      allele frequencies of 13 cardio-cerebrovascular risk polymorphisms were assessed
      and their possible association with dementia was investigated in a case-control
      study, including 221 consecutive unrelated subjects diagnosed with dementia (120
      subjects affected by AD, 55 by frontotemporal dementia, and 33 by vascular
      dementia) and 218 matched controls of Calabrian origin. RESULTS: Carriers of at
      least one APOEE4 allele resulted to be at higher risk of AD [OR(95% CI) =
      2.721(1.477-5.011)] and VaD [OR(95% CI) = 6.205(2.356-16.342)] compared to non
      carriers. Individuals with the IV genotype of the CETP polymorphism were more
      likely to have AD [OR(95% CI) = 2.427(1.364-4.319)] and VaD [OR(95% CI) =
      3.649(1.455-9.152)] compared to subjects with the II-VV genotypes. CONCLUSION:
      CETP I405V polymorphism is likely a risk factor for AD and VaD in our cohort,
      independent of APOEE4 status. Unmodifiable genetic risk factors should be taken
      into account to promote a healthy lifestyle to prevent dementia.

PMID- 29332049
TI  - Free Heme and Amyloid-beta: A Fatal Liaison in Alzheimer's Disease.
AB  - While the etiology of Alzheimer's disease (AD) is still unknown, an increased
      formation of amyloid-beta (Abeta) peptide and oxidative processes are major
      pathological mechanism of the disease. The interaction of Abeta with free heme
      leads to the formation of peroxidase-active Abeta-heme complexes. However, enzyme
      kinetic data and systematic mutational studies are still missing. These aspects
      were addressed in this study to evaluate the role of Abeta-heme complexes in AD.
      The enzyme-kinetic measurements showed peroxidase-specific pH- and H2O2
      dependencies. In addition, the enzymatic activity of Abeta-heme complexes
      constantly increased at higher peptide excess. Moreover, the role of the Abeta
      sequence for the named enzymatic activity was tested, depicting human-specific
      R5, Y10, and H13 as essential amino acids. Also by studying Y10 as an endogenous
      peroxidase substrate for Abeta-heme complexes, ratio-specific effects were
      observed, showing an optimal dityrosine formation at an about 40-fold peptide
      excess. As dityrosine formation promotes Abeta fibrillation while free heme
      disturbs protein aggregation, we also investigated the effect of Abeta-heme
      complex-derived peroxidase activity on the formation of Abeta fibrils. The
      fluorescence measurements showed a different fibrillation behavior at strong
      peroxidase activity, leading also to altered fibril morphologies. The latter was
      detected by electron microscopy. As illustrated by selected in vivo measurements
      on a mouse model of AD, the disease is also characterized by Abeta-derived
      microvessel destructions and hemolytic processes. Thus, thrombo-hemorrhagic
      events are discussed as a source for free heme in brain tissue. In summary, we
      suggest the formation and enzymatic activity of Abeta-heme complexes as
      pathological key features of AD.

PMID- 29332050
TI  - Supplemental Retinal Carotenoids Enhance Memory in Healthy Individuals with Low
      Levels of Macular Pigment in A Randomized, Double-Blind, Placebo-Controlled
      Clinical Trial.
AB  - BACKGROUND: There is a biologically plausible rationale whereby the dietary
      carotenoids lutein (L), zeaxanthin (Z), and meso-zeaxanthin (MZ), which are
      collectively referred to as macular pigment (MP) in the central retina (macula),
      support the maintenance of cognition via their antioxidant and anti-inflammatory
      properties. OBJECTIVE: To investigate the impact of supplemental L, Z, and MZ on
      memory, executive function, and verbal fluency among healthy individuals with low
      MP levels. METHODS: In this double-blind, placebo-controlled, randomized clinical
      trial, subjects (n = 91; mean+/-SD age = 45.42+/-12.40; % male = 51.6) consumed a
      daily formulation of 10 mg L, 10 mg MZ, and 2 mg Z (n = 45) or placebo (n = 46)
      for 12 months. Cognitive domains assessed included verbal and visual learning,
      immediate and delayed memory, executive function, and verbal fluency. MP and
      serum carotenoid concentrations of L, Z, and MZ were also measured. RESULTS:
      Following 12-month supplementation, individuals in the active group exhibited
      statistically significant improvements in memory when compared to the placebo
      group (paired associated learning [PAL] memory score [rANOVA, p = 0.009]; PAL
      errors [rANOVA, p = 0.017]). Furthermore, the observed reduction in the number of
      errors made in the PAL task among those in the intervention group was positively
      and significantly related to observed increases in MP volume (p = 0.005) and
      observed increases in serum concentrations of L (p = 0.009). CONCLUSION: This
      randomized, double-blind, placebo-controlled clinical trial demonstrates a memory
      enhancing effect of daily supplementation with L, Z, and MZ in healthy subjects
      with low MP at baseline. The implications of these findings for intellectual
      performance throughout life, and for risk of cognitive decline in later life,
      warrant further study.

PMID- 29332051
TI  - The Impact of Music on the Self in Dementia.
AB  - In this review, we consider how the onset and progression of dementia can disrupt
      one's sense of self, and propose that music is an ideal tool for alleviating this
      distressing symptom. Various aspects of the self can be impaired in people with
      dementia, depending on how the self is defined. There are anecdotal reports that
      music can 'bring people back to themselves' in the face of dementia, but there
      have been scarce empirical investigations of this topic. Motivated by a
      consideration of the existing literature, we outline a novel theoretical
      framework that accounts for the relationship between music and the self in people
      with dementia. We propose that music has a number of 'design features' that make
      it uniquely equipped to engage multiple aspects of the self. We suggest that each
      design feature interacts with different aspects of the self to varying degrees,
      promoting overall wellbeing. We discuss how existing research on music and
      dementia fits within this framework, and describe two case studies in which music
      was an ideal stimulus for reaffirming their sense of self. Our framework may be
      useful for the diagnosis and treatment of impairments of self in people with
      dementia, and highlights how music, given its ability to engage all aspects of
      the self simultaneously, can result in an overall enhanced sense of self.

PMID- 29332052
TI  - When Art Meets Gardens: Does It Enhance the Benefits? The Nancy Hypothesis of
      Care for Persons with Alzheimer's Disease.
AB  - The creation of healing gardens for persons with Alzheimer's disease and related
      diseases (ADRD) offers vast potential. They can play a role in the scaffolding of
      cognitive disorders, emotional stress, sensory processing, sense of harmony, and
      appeasement. These effects are achieved through a distributed interplay of
      psychological functions with the immediate environment and local culture on the
      one hand, and dialogue on the other. The garden, a natural canvas created by man,
      shares with art the ability to foster an esthetic sense for which the perception
      can be measured by functional neurological imaging exploration. Art represents a
      mediator for the collaborative realization of distributed psychological functions
      between different individuals. Based on the hypothesis of an optimization of the
      therapeutic potential of a garden by a design adapted to the neuro-psycho-social
      and cultural specificities of its users combined with the thoughtful introduction
      of an artistic dimension, the "art, memory and life" healing garden was created
      at the University Hospital of Nancy as a prototype for persons with ADRD. The
      design concept was based on two hypotheses that we formulate herein, discuss
      their theoretical foundation, and suggest enhanced design for therapeutic gardens
      based upon our experience.

PMID- 29332053
TI  - Apparent Cognitive Decline as Revealed by an Executive Function Test within a
      Cohort of Elderly Individuals Self-Reporting Normal Cognitive Performance.
AB  - Alzheimer's disease (AD) can be preceded by subtle memory decline that can last a
      decade or more before progressing to what would be diagnosed as the mild
      cognitive impairment stage. During this early stage of decline, individuals and
      even their caregivers can fail to perceive any serious difficulty or need to
      consult a physician. Herein, we present evidence in support of these concerns,
      and demonstrate how this can interfere not only with clinical trials of AD but
      also those involving cognitive performance of elderly individuals without
      intentional reference to AD.

PMID- 29332054
TI  - Dementia and Atrial Fibrillation: A Dangerous Combination for Ischemic Stroke and
      Mortality.
AB  - The risk of developing dementia is increased in patients with atrial fibrillation
      (AF), with the incidence of both conditions increasing with aging. Patients with
      dementia frequently do not receiving adequate thrombo-prophylaxis, because of the
      inability to monitor INR and/or to achieve and maintain good compliance with
      anticoagulant treatment. Under-treatment is therefore an important contributor to
      the increased risk of ischemic stroke and mortality in this subgroup of AF
      patients. In newly-diagnosed patients with AF starting oral anticoagulation, the
      presence of cognitive impairment should be considered in addition to the
      calculation of the SAMe-TT2R2 score, as part of an integrated decision management
      pathway to choose the most appropriate oral anticoagulant [i.e., vitamin K
      antagonists (VKAs) or non-vitamin K oral anticoagulants (NOACs)]. Moreover, in
      patients with low or worsening time in therapeutic range during VKAs therapy, the
      assessment of cognitive impairment may help identify those patients who may
      benefit from switching to NOACs. In conclusion, patients with AF and dementia
      benefit from anticoagulation and should not be denied receiving adequate stroke
      prevention. Cognitive function assessment and social support are pivotal elements
      in the management of these AF patients.

PMID- 29332055
TI  - Operating room scheduling and surgeon assignment problem under surgery durations
      uncertainty.
AB  - BACKGROUND: Scientific management methods are urgently needed to balance the
      demand and supply of heath care services in Chinese hospitals. Operating theatre
      is the bottleneck and costliest department. Therefore, the surgery scheduling is
      crucial to hospital management. OBJECTIVE: To increase the utilization and reduce
      the cost of operating theatre, and to improve surgeons' satisfaction in the
      meantime, a practical surgery scheduling which could assign the operating room
      (OR) and surgeon for the surgery and sequence surgeries in each OR was provided
      for hospital managers. METHODS: Surgery durations were predicted by fitting the
      distributions. A two-step mixed integer programming model considering surgery
      duration uncertainty was proposed, and sample average approximation (SAA) method
      was applied to solve the model. RESULTS: Durations of various surgeries were log
      normal distributed respectively. Numerical experiments showed the model and
      method could get good solutions with different sample sizes. CONCLUSIONS: Real
      life constraints and duration uncertainty were considered in the study, and the
      model was also very applicable in practice. Average overtime of each OR was
      reducing and tending to be stable with the number of surgeons increasing, which
      is a discipline for OR management.

PMID- 29332056
TI  - Ozone injection with or without percutaneous microdiscectomy for treatment of
      cervical disc herniation.
AB  - OBJECTIVE: This retrospective study compared the efficacy of combined
      percutaneous ozone injection and percutaneous discectomyto percutaneous ozone
      injection alone for the treatment of cervical disc herniation. METHODS: Patients
      with cervical disc herniation who were enrolled in our hospital from October 2010
      to June 2015 were divided into two groups: 1) treated with percutaneous ozone
      injection alone (control; n= 19); and 2) those treated with combined ozone
      injection and percutaneous microdiscectomy (combined treatment; n= 28). The
      efficacy of the combined treatment was evaluated relative to the control by
      visual analogue scale (VAS) and the modified Macnab standard. Effective treatment
      was defined as excellent or good, and ineffective as fair or poor. RESULTS: No
      major complications occurred in either group. For the control group, the VAS
      scores dropped from 6.75 +/- 2.34 before surgery to 2.78 +/- 1.85 immediately
      after surgery, and to 4.18 +/- 1.46 during the follow-ups. For patients who
      received the combined treatment, the VAS scores were 7.12 +/- 2.03 before
      surgery, 3.86 +/- 2.87 immediately after surgery, and 3.27 +/- 1.53 during the
      follow-ups. At the 6-month follow-up, 73.7% (14 from 19 patients) in the control
      group and 89.2% (25 from 28 patients) in the treatment group were judged to have
      received effective treatment. Difference in efficacy between two groups of
      treatment was statistically significant (P= 0.033). CONCLUSION: The rate of
      effective treatment in patients who received combined percutaneous
      microdiscectomy and ozone injection was higher than that of patients who received
      ozone injection alone. Combination of percutaneous microdiscectomy and ozone
      injection might be an effective method to treat patients with cervical disk
      hernia.

PMID- 29332057
TI  - Evaluation of thickness of CAD/CAM fabricated zirconia cores by digital
      microscope.
AB  - Despite several advantages of digitalized workflow, researchers have noted
      discrepancies in the precision and trueness. This study investigated the accuracy
      in the final thickness of Zirconia (Zr) cores fabricated by five CAD/CAM systems.
      Standardized manufacturing of the cores with 1 mm thickness were carried out.
      Cores were then sectioned into two halves and measurement made with Digital
      Microscope at 5 points in micrometers. Overall, mean thickness for the groups was
      1048.81 +/- 94.01, which was 48 MUm higher than the thickness programmed in the
      software. Anova showed a statistically significant difference between the groups
      (p= 0.000). Presence of variations in the thickness and 5 measurement points for
      the CAD/CAM systems investigated was found. No significant difference was
      observed and the thickness of the cores were within acceptable level.

PMID- 29332058
TI  - 3D surface-imaging for volumetric measurement in people with obesity.
AB  - BACKGROUND: Current methods for tracking the progress of people with obesity
      towards a weight loss goal appear simple and potentially misleading. A technique
      to quantify change in body shape whilst visualising areas of the body where
      weight loss occurs would be advantageous, and has the potential to be used as a
      motivational tool. Three-dimensional (3D) surface-imaging would serve as a good
      basis for such a technique, however current systems are prohibitively expensive.
      OBJECTIVE: Highlight the use of a cheaper alternative 3D surface-imaging system
      for volumetric measurement in people with obesity. METHODS: A recently developed
      low-cost 3D surface-imaging system was used, having previously being validated in
      a healthy population. A total of 61 people with obesity, enrolled on a weight
      loss programme, were surface-imaged using the system. RESULTS: The findings
      suggest the low-cost system can obtain 3D surface-images of an obese human body,
      from which numerical parameters could be calculated and further analysis
      conducted. CONCLUSIONS: Further studies will focus on the validity and
      reliability of such analyses and the potential of the system to be considered as
      a long-term instalment in primary healthcare settings as a weight loss aid.

PMID- 29332059
TI  - Analysis of skeletal muscle performance using piezoelectric film sensors.
AB  - A flexible piezoelectric thin film sensor has been proposed recently in several
      studies for detection of muscle movements. The objective of this study was to
      investigate the ability of this sensor to assess skeletal muscle performance and
      fatigue under isokinetic contractions. Simultaneous noninvasive measurements of
      muscles activity were done using surface electromyography (EMG) electrodes and
      two thin film piezoelectric sensors. Measurements were taken from the biceps
      during slow and fast elbow flexion with and without strong grip, during different
      weight lifting and from the gastrocnemius during treadmill marching at speeds of
      4 and of 10 kph. The results shows correlation between the onset of EMG and the
      piezoelectric sensors (Piezo) signals during muscle contraction. Increasing
      contraction intensity increase significantly both EMG and Piezo signals. Higher
      contractions velocity increased Piezo signal. Opposite linear relation was found
      between the average maximal EMG envelope amplitudes and the average maximal Piezo
      peaks with increasing loads. The significant decrease in the maximal Piezo peaks
      with time of all 3 subjects during elbow flexion while holding weight suggests
      the ability of piezoelectric thin film sensor to track muscle fatigue during
      isokinetic contractions.

PMID- 29332060
TI  - Information technology as a tool for the Italian Institute of Social Security
      (INPS) in the management of social security and civil disability: Pro and cons.
AB  - We examine, from a medical-legal perspective, the pro and cons of the information
      technology procedures that the Italian Institute of Social Security (INPS) has
      implemented to manage the provision of social disability assistance, meaning that
      separate from the payment of pension contributions, being welfare, anchored to an
      administrative requirement by way of the compulsory payment of a minimum social
      security contribution.

PMID- 29332061
TI  - Design and implementation of an advanced telemedicine model for the rural people
      of Bangladesh.
AB  - OBJECTIVES: Telemedicine based healthcare service faces different difficulties
      especially in the remote people of Bangladesh. The objective of this study was to
      implement an advanced telemedicine model in order to provide the healthcare
      services for the rural people of Bangladesh. METHODS: We developed the
      telemedicine model using an ardunio based low cost portable telemedicine tool kit
      by interfacing android application. Then we collected ECG, blood pressure,
      temperature, concentration of glucose in blood, SPO2, body position, airflow,
      height and weight through our developed model. Moreover, we designed a server for
      storing the recorded signal from the patients in order to treat them by health
      care professionals. Finally, this model is successfully tested with the patients
      of Marie Stopes Bangladesh Hospital Dhaka. RESULTS: We have removed noise from
      the recorded signal successfully through our developed hardware and software
      based techniques. Real time data were visualized to the expert doctor in order to
      prescribe them through our model. CONCLUSIONS: These results support that rural
      patient vital information can be collected in an automated way through the
      advanced model. Both rural and urban doctors can share and exchange patient
      information more effectively for the treatment of patient. The results of this
      research indicated that our developed telemedicine system can be used effectively
      in order to deliver healthcare services for the rural people of Bangladesh.

PMID- 29332062
TI  - Cytologic Features of Malignant Melanoma with Osteoclast-Like Giant Cells.
AB  - BACKGROUND: Malignant melanoma showing numerous osteoclast-like giant cells
      (OGCs) is an uncommon morphologic phenomenon, rarely mentioned in the cytologic
      literature. The few reported cases seem to have an aggressive clinical behavior.
      Although most findings support monocyte/macrophage differentiation, the exact
      nature of OGCs is not clear. CASE: A 57-year-old woman presented with an inguinal
      lymphadenopathy. Sixteen years before, cutaneous malignant melanoma of the lower
      limb had been excised. Needle aspiration revealed abundant neoplastic single
      cells as well as numerous multinucleated OGCs. Occasional neoplastic giant cells
      were also present. Nuclei of OGCs were monomorphic with oval morphology and were
      smaller than those of melanoma cells. The immunophenotype of OGCs (S100-, HMB45-,
      Melan-A-, SOX10-, Ki67-, CD163-, BRAF-, CD68+, MiTF+, p16+) was the expected for
      reactive OGCs of monocyte/macrophage origin. The tumor has shown an aggressive
      behavior with further metastases to the axillary lymph nodes and oral cavity.
      CONCLUSION: Numerous OGCs are a rare and relevant finding in malignant melanoma.
      Their presence should not induce confusion with other tumors rich in osteoclastic
      cells. Since a relevant number of OGCs in melanoma may mean a more aggressive
      behavior, and patients may benefit from specific treatments, their presence
      should be mentioned in the pathologic report.

PMID- 29332063
TI  - Diffusion Tensor Imaging Investigation of Uncinate Fasciculus Anatomy in Healthy
      Controls: Description of a Subgenual Stem.
AB  - The uncinate fasciculus is the largest white matter association tract connecting
      the prefrontal cortex and the anteromedial temporal lobe. The traditional
      anatomical description outlines a temporal stem that hooks around the posterior
      insula, a subinsular body, and 2 prefrontal stems extending to the lateral
      orbital gyri and the frontopolar cortex. Recent imaging studies of the white
      matter tracts deep to the subgenual cingulate gyrus (Brodmann area 25: BA25)
      suggest the presence of white matter fibers extending from BA25 to the amygdala,
      via a route that would run in close proximity to the uncinate fasciculus, that
      are of functional importance in mood disorders. We hypothesized that these fibers
      represent a third, medial prefrontal stem of the uncinate fasciculus. Using
      diffusion tensor imaging in 74 healthy volunteer humans, we seeded the uncinate
      fasciculus using 2 regions of interest centered over the temporal stem and the
      caudal body of the uncinate fasciculus in the coronal plane at the level of the
      anterior commissure. A medial prefrontal stem extending to the subgenual
      cingulate gyrus was demonstrated in 65/74 left and 70/74 right cerebral
      hemispheres, and had a mean fractional anisotropy value of 0.43 (95% CI 0.40
      0.47). The medial subgenual stem fibers were inseparable from the caudal body and
      temporal stem of the main uncinate fasciculus and followed the same hook-shaped
      morphology. A probable medial subgenual prefrontal stem of the uncinate
      fasciculus was demonstrated in a cohort of healthy volunteers and is of potential
      significance in our understanding of neuropsychiatry and mood disorders.

PMID- 29332064
TI  - Recurrent Intragenic Duplication within the NR5A1 Gene and Severe Proximal
      Hypospadias.
AB  - A heterozygous intragenic duplication within the repeated area (CTGCAGCTG)*2 of
      the NR5A1 gene was found in a 15-year-old 46,XY DSD (disorders/differences of sex
      development) patient with micropenis and severe proximal hypospadias. This
      heterozygous duplication has already been described twice in boys with a similar
      phenotype, whereas a deletion of 3 amino acids at the same position in the
      protein SF-1 has been described in a 46,XX patient with primary ovarian failure
      and short stature. These data suggest that this region within the NR5A1 gene has
      an important role for SF-1 protein function in gonads and is a hotspot for
      intragenic rearrangements.

PMID- 29332065
TI  - A Novel Mutation of AMHR2 In Two Siblings with Persistent Mullerian Duct
      Syndrome.
AB  - Persistent mullerian duct syndrome (PMDS) is characterized by the presence of
      mullerian duct derivatives in otherwise phenotypically normal males. It is caused
      in approximately 85% of the cases by mutations in the AMH gene or its type II
      receptor (AMHR2). We report on 2 brothers with normal external genitalia but high
      serum AMH levels. Sequence analysis of the AMHR2 gene in the 2 siblings revealed
      a novel homozygous missense mutation in exon 10 (p.V458L, c.1372G>T). PMDS is a
      rare condition, but it has to be considered in differential diagnosis of
      cryptorchidism with normal male genitalia.

PMID- 29332066
TI  - Correlation between Serum Calcineurin Activity and Left Ventricular Hypertrophy
      in Hypertensive Patients and Its Clinical Significance.
AB  - OBJECTIVE: The aim of this study is to investigate the correlation between
      calcineurin (CaN) and hypertension with left ventricular hypertrophy (HLVH) and
      to evaluate its potential clinical significance. DESIGN: The study involved 160
      patients diagnosed with hypertension and 42 controls. Based on the exclusion
      criteria, 42 were not eligible for this study. The remaining 118 hypertensive
      patients were categorized into 2 subgroups based on left ventricular mass index
      and relative ventricular wall thickness: a normal model subgroup with
      hypertension (HNM) and an HLVH subgroup. Serum CaN levels were determined by
      enzyme-linked immunosorbent assay, while serum CaN activity was determined by
      malachite green colorimetric assay. RESULTS: Among the HNM and HLVH subgroups, a
      positive correlation was demonstrated between serum CaN activity, but not serum
      CaN level, and HLVH. Moreover, the HLVH subgroup displayed a remarkable increase
      in the levels of brain natriuretic peptide, cystatin C, urinary
      albumin/creatinine ratio, and left atrium diameter compared to the HNM subgroup
      and controls. CONCLUSION: There was a positive correlation between serum CaN
      activity and LVH in hypertensive patients. Activated CaN could play an important
      role in the pathophysiologic mechanism of HLVH. Serum CaN activity could be a
      clinically useful diagnostic and prognostic biomarker for LVH.

PMID- 29332067
TI  - Incidence of and Risk Factors for Residual Anastomoses in Twin-Twin Transfusion
      Syndrome Treated with Laser Surgery: A 15-Year Single-Center Experience.
AB  - OBJECTIVES: To evaluate the incidence of residual anastomoses (RA) after laser
      therapy for twin-twin transfusion syndrome (TTS) and investigate risk factors for
      incomplete laser surgery. MATERIAL AND METHODS: All available TTS placentas
      treated with laser at our center between 2002 and 2016 were injected with color
      dye to assess the presence of RA. We evaluated the incidence of RA over the past
      15 years by dividing the cohort into three time periods, and studied the
      association with risk factors and neonatal outcome. RESULTS: Overall, RA were
      detected in 21.0% (78/371) of placentas. The incidence of RA decreased from 38.8%
      (26/67) in the initial period to 11.7% (16/137) in the most recent period (p <
      0.001). On multivariate analysis, several risk factors were independently
      associated with the risk of RA, including Solomon laser technique (odds ratio
      [OR] 0.17, 95% CI 0.09-0.33) and estimation of surgical success (OR 19.28, 95% CI
      8.17-45.49). Premature delivery and neonatal morbidity occurred more often in TTS
      cases with RA. CONCLUSIONS: The incidence of RA after laser therapy for TTS
      decreased significantly in the past 15 years and is now below 15% due to the use
      of the Solomon technique.

PMID- 29332068
TI  - The Role of Preoperative Steroids for Hearing Preservation Cochlear Implantation:
      Results of a Randomized Controlled Trial.
AB  - OBJECTIVES: To determine whether preoperative steroids can improve hearing
      outcomes in cochlear implantation (CI). METHODS: This is a randomized controlled
      trial involving 30 postlingual deaf CI patients. Subjects had preoperative
      thresholds of better than or equal to 80 dB at 125 and 250 Hz, and better than or
      equal to 90 dB at 500 and 1,000 Hz. The subjects were randomized to a control
      group, an oral steroid group (receiving 1 mg/kg/day of prednisolone for 6 days
      prior to surgery), or a transtympanic steroid group (receiving a single dose of
      0.5 mL of 10 mg/mL dexamethasone at 24 h prior to surgery). RESULTS: The subjects
      receiving transtympanic steroids had a significant decrease in the pure tone
      average over 3 months compared to the control and oral steroid group, which
      persisted over 12 months (p < 0.05). CONCLUSION: A single dose of preoperative
      transtympanic steroids prior to CI appears to have a beneficial effect, at least
      in the short term, with minimal effects seen in the longer term.

PMID- 29332069
TI  - The History of Movement Disorder Brain Surgery.
AB  - The first surgical procedures for abnormal movement disorders began in the 1930s,
      when surgeons first proposed ablative techniques of the caudate nucleus or
      transection of motor (pyramidal) pathways to reduce involuntary movements in
      patients with Parkinson's related tremor. During the 50-year interval between
      1945 and 1995, the development of precise intracranial guiding devices, brain
      maps, and advanced imaging led to the refinement of appropriate deep brain
      targets affecting extrapyramidal pathways. Lesional surgery and subsequent
      neuroaugmentation using deep brain stimulation extended the role of deep brain
      surgery for a wider group of patients with tremor, rigidity, dyskinesia, and
      other involuntary movement disorders. Stereotactic radiosurgery has had wide
      application for tremor. The history of movement disorder surgery reads like a
      who's who of brilliant and resourceful surgeons who pushed the frontiers of
      neurosurgery. Even today, practitioners of functional brain surgery are among the
      most innovative practicing neurosurgeons.

PMID- 29332070
TI  - Pathophysiologic Basis of Movement Disorders.
AB  - Movement disorders are common and functionally disabling neurologic diseases.
      Studies over the last decades have investigated the pathophysiology of these
      diseases in considerable detail, leading to significant insights into their
      generation of motor disability. While genetically and clinically heterogeneous,
      most of them are accompanied by prominent and characteristic changes in firing
      rates and patterns in the basal ganglia, thalamus, and cortex. In recent years,
      researchers have placed increasing emphasis on the importance of oscillatory
      changes in firing in these structures, and have discovered that brain areas that
      were previously considered to be remote from the basal ganglia (such as the
      cerebellum and the pedunculopontine nucleus) are also highly significant in these
      disorders. The evolving pathophysiologic concepts have important implications for
      improving our understanding of the biology of these disorders, and for the
      development of more effective pharmacologic and surgical therapies with fewer
      side effects than seen with the currently available treatments. In this chapter,
      the known pathophysiology of three common movement disorders, Parkinson's
      disease, dystonia, and essential tremor, is reviewed.

PMID- 29332071
TI  - Clinical Presentation and Prognosis of Common Movement Disorders.
AB  - Great progress has been made in expanding our understanding of the natural
      history of movement disorders, leading to impressive advancements in their
      medical and surgical management. Movement disorders are a diverse group of
      diseases, varying widely in clinical characteristics and evolution. Some are
      monosymptomatic while others have associated motor and nonmotor features. Some
      are static while others follow a progressive course. This chapter will review
      common primary and secondary movement disorders: Parkinson disease and other
      forms of Parkinsonism, essential tremor and its differential diagnoses, dystonia
      and tic disorders. Herein, we will provide an overview of the clinical
      presentation and prognosis of the primary and secondary movement disorders most
      relevant to discussions of surgical candidacy.

PMID- 29332072
TI  - Medical Management of Movement Disorders.
AB  - Pharmacological treatment is the cornerstone in the management of movement
      disorders. Although most available treatment options have no impact on the
      underlying process of each movement disorder, symptomatic therapies can
      significantly improve patient's quality of life and level of disability. Here, we
      review the current knowledge on clinical symptomatic management of Parkinson's
      disease (both early and advanced stages), essential tremor, dystonia, and chorea.
      Ideally, treatment should be carried out by specialists with reasonable
      experience in movement disorders, as it needs to be tailored for each patient
      depending on several appraisals, including but not limited to patients' needs,
      compliance issues, potential side effects, caregiver support, and presence of
      comorbidities. When medications fail to improve patient's disability,
      stereotactic surgery is a well-established option for most of these disorders.

PMID- 29332073
TI  - Functional Anatomy of Basal Ganglia Circuits with the Cerebral Cortex and the
      Cerebellum.
AB  - The neural connections of the basal ganglia provide important insights into their
      function. Here, we discuss the current perspective on basal ganglia connections
      with the cerebral cortex and with the cerebellum. We review the evidence that the
      basal ganglia participate in functionally segregated circuits with motor and non
      motor areas of the cerebral cortex. We then discuss the data that the basal
      ganglia are interconnected with the cerebellum. These results provide the
      anatomical substrate for basal ganglia contributions not only to the control of
      movement, but also to a variety of cognitive and affective functions.
      Furthermore, these findings indicate that abnormal activity in basal ganglia
      circuits with the cerebral cortex and with the cerebellum may contribute to both
      motor and non-motor deficits associated with several neurologic and psychiatric
      conditions.

PMID- 29332074
TI  - Diffusion Tensor Imaging of the Basal Ganglia for Functional Neurosurgery
      Applications.
AB  - Since its introduction, diffusion tensor imaging (DTI) has become an important
      tool in neuroscience given its unprecedented ability to image brain white matter
      in vivo. The interest in understanding the mechanisms of action of Deep Brain
      Stimulation in different targets and indications, together with the constant
      drive towards the improvement in long-term clinical outcomes, has found a logical
      complement in the application of tractography in this field. Diffusion tensor
      imaging has been traditionally associated with an increased susceptibility to MRI
      artifacts, and expensive computational resources. Recent advances have however
      improved these restrictions, allowing for countless applications in Neurosurgery,
      as demonstrated by the large number of original research papers published in the
      last decade. In this chapter, we review the current status of the implementation
      of DTI during DBS of the basal ganglia, discussing the findings, potential
      challenges and the expected improvements in surgical outcomes deriving by the
      routine use of tractography in functional neurosurgery.

PMID- 29332075
TI  - Patient Evaluation and Selection for Movement Disorders Surgery: The Changing
      Spectrum of Indications.
AB  - This report summarizes the state-of-the-art and controversies around patient
      selection for deep brain stimulation (DBS) for various conditions. Parkinson's
      disease (PD): several class I studies have shown superiority of DBS over best
      medical treatment for advanced PD with fluctuations and further inclusion
      criteria. One class I study suggests that PD patients with early motor
      complications might gain more quality of life if operated within 3 years after
      the onset of fluctuations. The subthalamic nucleus (STN) is still the standard
      target. STN DBS has an impact on impulse control disorders though the exact
      mechanism is unclear. Tremor: essential tremor (ET) patients found to be eligible
      for DBS surgery should first be treated with primidone, propranolol, and with a
      combined therapy preoperatively. Second-line drugs (i.e., topiramate and
      gabapentin) may be useful. No class I studies exist for DBS treatment of ET. The
      optimal target of DBS in ET might be the posterior subthalamic area. Dystonia:
      there is class I evidence for primary generalized and segmental dystonia and for
      some botulinum-resistant focal dystonias. The impact of age, symptom duration,
      and DYT-mutation status in primary dystonia on the outcome of DBS surgery clearly
      demands more studies. DBS has a role in SCGE-mutation positive myoclonus dystonia
      and tardive dystonia. Finally, neurostimulation in secondary dystonia might be
      considered in selected patients based on an individual patient's approach.

PMID- 29332077
TI  - Stereotactic Radiofrequency Lesioning for Movement Disorders.
AB  - During the past 2 decades, deep brain stimulation (DBS) took over the position of
      radiofrequency (RF) lesioning of thalamic or pallidal targets for control of
      movement disorders. Superiority of DBS over RF lesioning is widely accepted, and
      most neurosurgeons even regard RF lesioning to be old-fashioned and dangerous.
      Such concepts emerged from the data of old stereotactic operations with
      ventriculography and without computerized planning. Hardware-related
      complications are not negligible in long-term DBS therapy, and DBS only controls
      the symptoms. Living with an implanted device is also a burden for patients. With
      modern stereotactic techniques, RF lesioning is safe and effective. Indication of
      RF lesioning includes various types of tremor, focal hand dystonia, and even
      generalized or segmental dystonias. Neurosurgeons armed with both the procedures
      can choose the best treatment modality for patients.

PMID- 29332076
TI  - Image-Guided, Asleep Deep Brain Stimulation.
AB  - Deep brain stimulation (DBS) has become an established treatment for medically
      refractory movement disorders including Parkinson's disease, essential tremor,
      and dystonia. The field of DBS continues to evolve with advances in patient
      selection, target identification, electrode and pulse generator technology, and
      the development of more effective stimulation paradigms such as closed-loop
      stimulation. Furthermore, as the safety and efficacy of DBS improves through
      better hardware design and deeper understanding of its mechanisms of action, the
      indications for DBS will continue to expand to cover a wider range of disorders.
      Finally, the recent approval of MR-guided focused ultrasound for the treatment of
      essential tremor and potentially other movement disorders heralds a resurgence in
      lesion creation as a viable alternative to DBS for selected patients.

PMID- 29332078
TI  - Magnetic Resonance-Guided High Intensity Focused Ultrasound for Treating Movement
      Disorders.
AB  - Transcranial magnetic resonance-guided focused ultrasound (MRgFUS) surgery has
      recently gained favor as a novel, noninvasive alternative to conventional
      neurosurgery. In contrast to traditional ablative interventions, transcranial
      MRgFUS surgery is entirely imaging-guided and uses continuous temperature
      measurements at the target and surrounding tissue taken in real-time. Unlike
      Gamma Knife radiosurgery, MRgFUS surgery can make a lesion immediately and does
      not use ionizing radiation. Moreover, since no metallic device is implanted, MR
      imaging-based diagnosis is not restricted throughout life. An additional strength
      of transcranial MRgFUS surgery is its ability to focus acoustic energy through
      the intact skull onto deep-seated targets, while minimizing adjacent tissue
      damage. Even though the established indications of MRgFUS include bone
      metastases, uterine fibroids, and breast lesions, several promising preclinical
      and phase I clinical trials of neuropathic pain, essential tremor, Parkinson's
      disease (PD), and obsessive-compulsive disorder have demonstrated that the
      delivery of focused ultrasound energy promises to be a broadly applicable
      technique. For instance, this technique can be used to generate focal
      intracranial thermal ablative lesions of brain tumors, or to silence
      dysfunctional neural circuits and disrupt the blood-brain barrier for targeted
      drug delivery and the modulation of neural activity. Here we review the general
      principles of MRgFUS and its current applications, with a special focus on
      movement disorders such as essential tremor and PD, and discuss controversies and
      limitations of this technique.

PMID- 29332079
TI  - Radiosurgical Thalamotomy.
AB  - Tremor is a common movement disorder that can be disabling, and its initial
      treatment is in the form of medical therapies. Often patients are refractory and
      seek surgical intervention. Treatment options for these patients include surgical
      radiofrequency thalamotomy and deep brain stimulation. There are a subset of
      patients who, for various reasons, are not candidates for open surgical
      procedures, or who opt to avoid them. For these patients, radiosurgical
      thalamotomy is a safe and useful alternative. Herein, we provide a review of the
      use of radiosurgical thalamotomy for the treatment of medically refractory tremor
      by discussing its history, defining the technique and its indications, evaluating
      its efficacy, and exploring its complications and shortcomings.

PMID- 29332080
TI  - Radiosurgical Pallidotomy for Parkinson's Disease.
AB  - Deep brain stimulation (DBS) has been widely accepted as a tool for treating many
      symptoms of Parkinson's disease (PD); pallidotomy has been nearly abandoned.
      Concerns about both the safety and efficacy of pallidotomy are based on small
      series, isolated case reports, and techniques that would now be considered
      obsolete. The senior author recently reviewed long-term follow-up of a series of
      patients who had gamma knife pallidotomy (GKP) for advanced PD. GKP leads to
      durable, clinically significant benefit. Bilateral GKP adds incremental
      improvement. The complication rate was 4% when calculated on a per lesion basis.
      GKP is not quite as effective as DBS for tremor and bradykinesia; the results of
      GKP and DBS are equivalent for dyskinesia. GKP should be considered in patients
      who are not candidates for DBS. GKP is not as invasive as radiofrequency
      pallidotomy and avoids the problems and expenses associated with DBS. Patients on
      anticoagulants, with cognitive deficits or with other contraindications to DBS
      can be offered GKP to alleviate many of the motor symptoms of PD.

PMID- 29332081
TI  - Radiosurgical Subthalamic Nucleotomy.
AB  - Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is the reference
      technique in Parkinson's disease (PD) at different stages of complications. Some
      patients cannot afford DBS due to anticoagulation or comorbidities or due to
      pecuniary reasons. Radiosurgery is a minimally invasive stereotactic technique,
      with no craniotomy and subsequently no risk of bleeding or infection. Its good
      safety efficacy profile has been established in the treatment of tremor, and the
      postoperative care issues are simple with a much shorter hospital stay (mean 48
      h). The application of radiosurgery to STN target in PD as an alternative to DBS
      is being debated. The lesion of the STN is presumed to induce hemiballism.
      Experimental works suggest a potential lower risk of hemiballism in animal models
      of PD. However, radiofrequency ablation of the STN is associated with a
      significant rate of severe dyskinesia, sometimes permanent and severe enough to
      request salvage pallidotomies. The positive experience of VIM radiosurgery in
      tremor and its capacity to create precise, accurate and well-controlled lesions
      provides reasonable rationale for the evaluation of this technique when applied
      to STN in PD. Preliminary results till date have shown the absence of severe
      permanent dyskinesia. Prospective controlled trials are mandatory to evaluate the
      safety efficacy of this technique in PD.

PMID- 29332082
TI  - Frameless Functional Stereotactic Approaches.
AB  - The stereotactic frame has served as the gold standard apparatus for accurate and
      precise targeting of deep brain structures since 1947. Despite passing the test
      of time, the stereotactic frame has several limitations from the perspective of
      both neurosurgeons and patients. Therefore, there was a need to develop a
      frameless system that had equivalent accuracy and reliability to the frame. This
      need was met with 3 commercially available frameless stereotactic systems
      designed specifically for deep brain stimulation surgery: Nexframe, STarFix, and
      ClearPoint. Over the past decade, the frameless and frame-based systems have been
      extensively investigated by numerous studies and found to be equivalent in
      experimental and clinical accuracy as well as in clinical outcomes. This chapter
      summarizes the findings of those studies along with the discussion of sources of
      stereotactic errors. The procedural aspects, advantages, and disadvantages of
      each frameless system are reviewed. Frameless stereotaxy is a safe, accurate, and
      effective technique for functional stereotactic approaches and provides a viable
      alternative to the frame-based systems.

PMID- 29332083
TI  - Deep Brain Stimulation: Interventional and Intraoperative MRI Approaches.
AB  - Interventional and intraoperative MRI approaches to deep brain stimulator
      implantation are relatively new, and in their purest form represent a distinct
      departure from traditional stereotactic techniques. They employ a novel means of
      stereotaxis based on regions of interest in the MR space and simple geometric
      principles, which eliminate the need for a stereotactic frame. This approach is
      appropriate for targets that are MR visible, and for whom the local anatomy and
      function are well characterized. It may also be appropriate for targets that do
      not have a well-described physiologic signature and for which clinical response
      to macrostimulation does not play a critical role. We will discuss the rationale
      and principles of this new technique as well as its advantages and disadvantages
      relative to awake, physiologically guided deep brain stimulation surgery.

PMID- 29332084
TI  - Thalamic Deep Brain Stimulation.
AB  - The use of deep brain stimulation (DBS) of the thalamus has been proven to be a
      safe and efficacious treatment for the management of many diseases. The most
      common indication for thalamic DBS remains essential tremor (ET), one of the most
      common movement disorders in the world. ET patients should be considered for
      surgical intervention when their tremor has demonstrated to be refractory to
      medication, a characteristic estimated to be present in roughly 50% of ET cases.
      Advantages of DBS over thalamotomy include its reversibility, the ability to
      adjust stimulation settings to optimize efficacy and minimize side effects, the
      ability to perform bilateral procedures safely, and an association with a lower
      risk of postoperative cognitive problems. The most common target of DBS for ET is
      the ventralis intermedius (VIM) of the thalamus, and the optimal electrode
      location corresponds to the anterior margin of the VIM. Other indications for
      thalamic DBS include non-ET tremor, obsessive-compulsive disorder, neuropathic
      pain, traumatic brain injury, Tourette's syndrome, and drug-resistant epilepsy
      among others.

PMID- 29332085
TI  - Deep Brain Stimulation of the Subthalamic Nucleus and Globus Pallidus for
      Parkinson's Disease.
AB  - The concept of deep brain stimulation (DBS) for Parkinson's disease (PD) was
      introduced over 20 years ago, but our understanding of the nuances of this
      procedure continues to improve. The average motor outcomes of internal segment of
      the globus pallidus (GPi) and subthalamic nucleus (STN) DBS appear to be similar,
      although GPi DBS may allow greater recovery of verbal fluency and may provide
      greater relief of depression symptoms and improvement in the quality of life, and
      STN DBS appears more likely to result in decrease in levodopa equivalent doses.
      Despite the lack of consensus on whether STN or GPi DBS is most appropriate for a
      given clinical phenotype, the general expansion of patient selection criteria to
      include younger and older patients and the advent of real-time imaging-confirmed
      that DBS electrode placement are making life-changing treatment available to
      greater numbers of movement disorder patients.

PMID- 29332086
TI  - Current and Expected Advances in Deep Brain Stimulation for Movement Disorders.
AB  - Deep brain stimulation (DBS) has become an established treatment for medically
      refractory movement disorders including Parkinson's disease, essential tremor,
      and dystonia. The field of DBS continues to evolve with advances in patient
      selection, target identification, electrode and pulse generator technology, and
      the development of more effective stimulation paradigms such as closed-loop
      stimulation. Furthermore, as the safety and efficacy of DBS improves through
      better hardware design and deeper understanding of its mechanisms of action, the
      indications for DBS will continue to expand to cover a wider range of disorders.
      Finally, the recent approval of MR-guided focused ultrasound for the treatment of
      essential tremor and potentially other movement disorders heralds a resurgence in
      lesion creation as a viable alternative to DBS for selected patients.

PMID- 29332087
TI  - Adaptive Brain Stimulation for Movement Disorders.
AB  - Deep brain stimulation (DBS) has markedly changed how we treat movement disorders
      including Parkinson's disease (PD), dystonia, and essential tremor (ET). However,
      despite its demonstrable clinical benefit, DBS is often limited by side effects
      and partial efficacy. These limitations may be due in part to the fact that DBS
      interferes with both pathological and physiological neural activities. DBS could,
      therefore, be potentially improved were it applied selectively and only at times
      of enhanced pathological activity. This form of stimulation is known as closed
      loop or adaptive DBS (aDBS). An aDBS approach has been shown to be superior to
      conventional DBS in PD in primates using cortical neuronal spike triggering and
      in humans employing local field potential biomarkers. Likewise, aDBS studies for
      essential and Parkinsonian tremor are advancing and show great promise, using
      both peripheral or central sensing and stimulation. aDBS has not yet been trialed
      in dystonia and yet exciting and promising biomarkers suggest it could be
      beneficial here too. In this chapter, we will review the existing literature on
      aDBS in movement disorders and explore potential biomarkers and stimulation
      algorithms for applying aDBS in PD, ET, and dystonia.

PMID- 29332088
TI  - Drug Delivery for Movement Disorders.
AB  - There has been substantial research interest in delivering therapeutic
      neurotrophic factors directly to the brain for the treatment of Parkinson's
      Disease (PD) and other movement disorders. Direct infusion of glial cell-line
      derived neurotrophic factor has been investigated in both pre-clinical models and
      clinical trials. In this chapter we discuss past and present research
      investigating the potential of direct drug delivery to the brain for the
      treatment of PD and other movement disorders.

PMID- 29332089
TI  - Gene Therapy for Parkinson's Disease.
AB  - Gene therapy is a clinical tool that may eventually provide therapeutic benefit
      to patients suffering from movement disorders through a few potential mechanisms:
      direct correction of the pathogenic mechanism, neuroprotection, neurorestoration
      or symptom control. The therapeutic mechanism is therefore dependent on knowledge
      of disease pathogenesis and the required temporal and spatial specificities of
      gene expression. An additional critical challenge is achieving the most complete
      transduction of the target structure while avoiding leakage into neighboring
      regions or perivascular spaces. Although critical clinical work is ongoing to
      optimize the direct intracerebral delivery of transgenes to the brain, the field
      has recently entered a new technological era, where interventional-MRI-guided
      convection-enhanced delivery is the gold standard for verifying accurate vector
      delivery in real-time.

PMID- 29332090
TI  - Impaired Value of 99m Tc-GSA Scintigraphy as an Independent Risk Factor for
      Posthepatectomy Liver Failure in Patients with Hepatocellular Carcinoma.
AB  - BACKGROUND: Posthepatectomy liver failure (PHLF) was recently defined with the
      corresponding recommendations as follows: grade A, no change in clinical
      management; grade B, clinical management with noninvasive treatment; and grade C,
      clinical management with invasive treatment. In this study, we identified the
      risk factors for grade B and C PHLF in patients with hepatocellular carcinoma
      (HCC). METHODS: Of 339 HCC patients who underwent curative hepatic resection, 218
      were included for analysis. The LHL15 index (uptake ratio of the liver to that of
      the liver and heart at 15 min) was measured by 99m Tc-GSA (99m technetium
      labelled galactosyl human serum albumin); remnant LHL15 was calculated as LHL15 *
      [1 - (resected liver weight - tumor volume)/whole liver volume without tumor].
      RESULTS: A total of 163 patients were classified as having no PHLF, whereas 17,
      37, and 1 patient had PHLF grade A, B, and C, respectively. There were
      significant differences in indocyanine green R15, serum albumin, prothrombin
      time, Child-Pugh classification, LHL15 and remnant LHL15 between patients with
      grades B/C PHLF and patients with grade A or no PHLF. Only remnant LHL15 was
      identified as an independent risk factor for grades B/C PHLF (p = 0.023), with a
      cut-off value of 0.755. CONCLUSIONS: Remnant LHL15 was an independent risk factor
      for grades B/C PHLF. Patients with impaired remnant LHL15 value of <0.755 should
      be carefully monitored for PHLF.

PMID- 29332091
TI  - The Association among Default Mode Network Functional Connectivity,
      Mentalization, and Psychopathology in a Nonclinical Sample: An eLORETA Study.
AB  - AIMS: We investigated default mode network (DMN) electroencephalography (EEG)
      functional connectivity differences between individuals with self-reported high
      mentalization capability and low psychopathological symptoms, versus participants
      with mentalization impairments and high psychopathological symptoms. METHODS:
      Forty-nine students (35 women) with a mean age of 22.92 +/- 2.53 years were
      administered the Mentalization Questionnaire (MZQ) and the Symptom Checklist-90
      Revised. Five minutes of EEG during resting state were also recorded for each
      participant. DMN functional connectivity analyses were conducted by means of the
      exact Low Resolution Electric Tomography software (eLORETA). RESULTS: Compared to
      the individuals with high mentalization capability and lower self-reported
      psychopathological symptoms, participants with mentalization impairments and high
      psychopathological symptoms showed a decrease of EEG beta connectivity between:
      (i) the right and left medial frontal lobe, and (ii) the left medial frontal lobe
      and the right anterior cingulate cortex. Furthermore, while MZQ total score was
      positively associated with DMN network connections (i.e., right and left medial
      frontal lobes), several psychopathological symptoms (i.e., interpersonal
      sensitivity, depression, and psychoticism) were negatively associated with DMN
      connectivity. CONCLUSION: Our results may reflect a top-down emotion regulation
      deficit which is associated with both internalizing and externalizing behavior
      problems.

PMID- 29332092
TI  - Early Life Stress Activates Glial Cells in the Hippocampus but Attenuates
      Cytokine Secretion in Response to an Immune Challenge in Rat Pups.
AB  - OBJECTIVE: Early life stress (ELS) increases the vulnerability to developing
      psychopathological disorders in adulthood that are accompanied by brain
      inflammatory processes. However, it is not known how a combined double hit
      (stress and immune) at an early age affects the response of the neuroimmune
      system. Here we investigated the effect of periodic maternal separation (MS)
      followed by administration of lipopolysaccharide (LPS) on glial cells in the CA3
      region and hilus of the hippocampus and on cytokine release on postnatal day (PN)
      15. METHODS: Male rat pups were subjected to MS (3 h/day, PN1-14). MS and control
      pups received a single LPS injection (1 mg/kg of body weight) on PN14. They were
      subjected to an open field test 1 h later. The pups were sacrificed 90 min after
      LPS injection (PN14) or on PN15 for cytokine or immunohistological analyses,
      respectively. RESULTS: LPS reduced the locomotion and induced high corticosterone
      levels in treated pups. MS or LPS reduced microglial density and activated
      microglial cells in the hippocampal CA3 and hilus regions. Microglial activation
      was highest in MS-LPS pups. The astrocyte density was mildly reduced by MS or LPS
      in the CA3 region and hilus, but the reduction was maximal in MS-LPS pups. LPS
      increased the secretion of plasmatic interleukin (IL)-1beta, tumor necrosis
      factor-alpha, and IL-6, and of hippocampal IL-1beta protein, but these were
      attenuated in MS-LPS pups. CONCLUSION: Although MS and LPS activate neuroimmune
      cells, stress attenuates the hippocampal and peripheral cytokine response to LPS
      through an as-yet unidentified adaptive mechanism. These results provide
      information regarding the neurobiology of stress and inflammation.

PMID- 29332093
TI  - Structure-Function Correlation in Hemianopic Vision Loss in Children Aged 3-6
      Years Using OCT and SVOP, and Comparison with Adult Eyes.
AB  - PURPOSE: To correlate visual field assessment with saccadic vector optokinetic
      perimetry (SVOP) in children with ganglion cell loss due to anterior pathway
      pathologies resulting in hemianopic visual field defects measured with optical
      coherence tomography (OCT). METHODS: 5 young (aged 3-6 years) and 5 adult
      patients with hemianopia, 10 healthy preschoolers (mean age 4.4 years), and 10
      healthy adults (mean age 25.3 years) were tested with SVOP and OCT (focusing on
      the ganglion cell layer, GCL+). In adults, visual field testing was also
      performed with static and fundus-controlled perimetry. RESULTS: OCT allowed
      precise structure analysis and showed a vertical border with GCL+ loss on the
      hemianopic side in children and adults compared to controls. SVOP showed visual
      field defects on the hemianopic side in peripheral regions and inadequate results
      at the parafoveal positions in both groups. In contrast, static and fundus
      controlled perimetry showed a clear border in foveal and parafoveal regions.
      CONCLUSIONS: All children underwent SVOP with minimal restrictions, allowing
      functional evaluation of peripheral visual field positions. Parafoveal positions
      showed multiple false-positive results. The function-structure relationship is
      measurable even in young children by using the GCL+ analysis. This combination of
      novel child-friendly techniques allows collecting objectively measured values and
      simplifies diagnosis and follow-up in treatment.

PMID- 29332094
TI  - Low-Dose Oral Immunotherapy Using Low-Egg-Allergen Cookies for Severe Egg
      Allergic Children Reduces Allergy Severity and Affects Allergen-Specific
      Antibodies in Serum.
AB  - BACKGROUND: We evaluated the safety and efficacy of low-egg-allergen cookies
      (LAC) as low-dose oral immunotherapy (OIT) in children with severe egg allergy.
      We also examined the relationship between mild desensitization by low-dose OIT
      and serum biomarkers of allergy. METHODS: We enrolled 13 children with egg
      allergy who could not receive OIT with hard-boiled egg white (EW). For 11
      participants, OIT was carried out using LAC for 3-4 months. Open food challenges
      with hard-boiled EW and blood samplings were performed before and after OIT.
      Participants were divided into 2 groups: high effect (H-E) and no/low effect (N/L
      E). Serum levels of total IgE and egg yolk-, EW-, and ovomucoid (OM)-specific
      IgE, ovalbumin (OVA)- and OM-specific IgG4, IgA1, and IgA2, and the percentage of
      CD 203c+ were measured. RESULTS: Allergic severity was reduced in 7 patients, who
      were assigned to the H-E group. Moreover, no study participants were taken off
      the intake of LAC during OIT. In the H-E group, OVA-specific IgA2 levels after
      OIT were significantly higher than before OIT. The ratios of OM-specific IgG4/OM
      specific IgE and OM-specific IgA2/OM-specific IgE in the H-E group after OIT were
      significantly higher than before OIT. CONCLUSION: Our findings suggest that low
      dose OIT using LAC is an effective and safe treatment for patients with severe
      egg allergy.

PMID- 29332095
TI  - Both Serum Brain-Derived Neurotrophic Factor and Interleukin-6 Levels Are Not
      Associated with Therapeutic Response to Lamotrigine Augmentation Therapy in
      Treatment-Resistant Depressive Disorder.
AB  - BACKGROUND/AIMS: Serum levels of brain-derived neurotrophic factor (BDNF) and
      interleukin-6 (IL-6) were prospectively monitored in relation with therapeutic
      response to lamotrigine augmentation therapy in 46 (15 males and 31 females)
      inpatients with treatment-resistant depressive disorder during an 8-week
      treatment with lamotrigine using an open-study design. METHODS: The subjects were
      46 depressed patients who had already shown insufficient response to at least 3
      psychotropics including antidepressants, mood stabilizers, and atypical
      antipsychotics. The diagnoses were major depressive disorder (n = 19), bipolar I
      disorder (n = 6), and bipolar II disorder (n = 22). The final doses of
      lamotrigine were 100 mg/day for 26 subjects who were not taking valproate and 75
      mg/day for 20 subjects taking valproate, respectively. Depressive symptoms were
      evaluated by the Montgomery-Asberg Depression Rating Scale (MADRS) before and
      after the 8-week treatment. Blood sampling was performed before the start of
      lamotrigine treatment and at week 8. Serum BDNF and IL-6 levels were measured
      using quantitative sandwich enzyme immunoassays. RESULTS: No significant changes
      in serum BDNF or IL-6 levels during the 8-week lamotrigine treatment were
      observed in the total of subjects, responders or nonresponders. There was no
      significant correlation between the changes in serum BDNF or IL-6 levels and the
      percent improvement in MADRS scores in the overall subjects. CONCLUSION: The
      present study suggests that the acute effect of lamotrigine augmentation therapy
      for a major depressive episode is not related to either BDNF or IL-6, at least in
      patients with treatment-resistant depressive disorder.

PMID- 29332096
TI  - Higher Thrombin-Antithrombin III Complex Levels May Indicate Severe Acute
      Pancreatitis.
AB  - AIM: Coagulation disorders may develop in association with severe acute
      pancreatitis (AP). Plasma thrombin-antithrombin III complex (TAT) levels are one
      of the principal markers of coagulation disorder. The purpose of this study was
      to evaluate TAT and other hemostatic parameters in patients with AP and to
      examine whether or not these parameters indicate the severity of AP. METHOD:
      Forty-six patients with AP (14 severe, 32 non-severe) and a 30-member healthy
      control group were recruited. The severity of AP was determined using the revised
      Atlanta classification. ELISA was used to measure patients' plasma TAT levels.
      RESULTS: The TAT levels of AP patients at presentation were higher than those of
      the control group (p = 0.005). The plasma TAT levels of patients with severe AP
      were also significantly higher than those of patients with non-severe AP (p =
      0.05) and of the control group (p < 0.001). The general accuracy, sensitivity and
      specificity of TAT levels in predicting the severity of AP were 77.4, 77.8, and
      77.3% respectively. CONCLUSION: The coagulation cascade was activated in the AP
      patients in our study, and this was shown to become more pronounced as severity
      of the disease increased. Plasma TAT levels at the time of presentation in
      patients with AP can be used as a marker for predicting the severity of the
      disease.

PMID- 29332098
TI  - A Novel Mutation of the delta-Globin Gene in an Asymptomatic 30-Year-Old Female.

PMID- 29332097
TI  - Is the Atopy Patch Test Reliable in the Evaluation of Food Allergy-Related Atopic
      Dermatitis?
AB  - BACKGROUND: Aeroallergens and food allergens are found to be relevant in atopic
      dermatitis. The atopy patch test (APT) can help to detect food allergies in
      children with atopic dermatitis. This study evaluates if the APT is a valuable
      tool in the diagnostic workup of children with food allergy-related atopic
      dermatitis. METHODS: 42 children between 6 months and 12 years of age were
      selected at the Mofid Children Hospital. Atopic dermatitis was diagnosed, and the
      severity of the disease was determined. At the test visit, the patients underwent
      a skin prick test (SPT), APT, and serum IgE level measurement for cow's milk, egg
      yolk, egg white, wheat, and soy. RESULTS: We found a sensitivity of 91.7%, a
      specificity of 72.7%, a positive predictive value (PPV) of 88%, a negative
      predictive value (NPV) of 80%, and an accuracy of 85.7% for APT performed for
      cow's milk. APT performed for egg yolk had a sensitivity and a NPV of 100%, while
      the same parameters obtained with egg white were 84.2 and 75%, respectively. The
      sensitivity, specificity, and NPV of the APT for wheat were 100, 75, and 100%,
      respectively. The sensitivity, PPV, and NPV of the APT for soy were 87.5, 70, and
      87.5%, respectively. CONCLUSIONS: Our data demonstrate that the APT is a reliable
      diagnostic tool to evaluate suspected food allergy-related skin symptoms in
      childhood and infancy.

PMID- 29332099
TI  - Association between the Intron 8 VNTR Polymorphism of the DAT1 Gene and Crack
      Cocaine Addiction.
AB  - BACKGROUND: This study aims to compare allele and genotype frequencies of a 30-bp
      variable number of tandem repeats (VNTR) polymorphism of the DAT1 gene, located
      at intron 8, between adult crack cocaine users and nonaddicted individuals. Due
      to its involvement in drug addiction, this gene is a good candidate for molecular
      studies. METHODS: A cross-sectional sample of 239 current adult crack abusers or
      dependents from in- and outpatient clinics and 211 control individuals was
      collected in Brazil. They were evaluated using ASRS, ASI-6, WAIS-III, and MINI
      assessments. DNA samples extracted from whole blood were genotyped for the intron
      8 VNTR in DAT1. RESULTS: Logistic regression analysis was performed and
      controlled for gender, age, ethnicity, educational level, and comorbidities of
      clinical interest (generalized anxiety disorder, suicide risk, major depressive
      episode, and attention deficit/hyperactivity disorder). This analysis showed that
      the 6R6R genotype was associated with crack cocaine addiction (OR = 1.844; CI =
      1.101-3.089; p = 0.020). CONCLUSIONS: Our results are consistent with the role of
      DAT1 in the neurobiology of drug addiction. Nevertheless, the study of other
      genes, environmental factors, and their interactions is also important to gain a
      broader understanding of this condition.

PMID- 29332101
TI  - Is Kinesio Taping to Generate Skin Convolutions Effective for Increasing Local
      Blood Circulation?
AB  - BACKGROUND It is unclear whether traditional application of Kinesio taping, which
      produces wrinkles in the skin, is effective for improving blood circulation. This
      study investigated local skin temperature changes after the application of an
      elastic therapeutic tape using convolution and non-convolution taping methods
      (CTM/NCTM). MATERIAL AND METHODS Twenty-eight pain-free men underwent CTM and
      NCTM randomly applied to the right and left sides of the lower back. Using
      infrared thermography, skin temperature was measured before, immediately after
      application, 5 min later, 15 min later, and after the removal of the tape.
      RESULTS Both CTM and NCTM showed a slight, but significant, decrease in skin
      temperature for up to 5 min. The skin temperature at 15 min and after the removal
      of the tape was not significantly different from the initial temperature for CTM
      and NCTM. There were also no significant differences in the skin temperatures
      between CTM and NCTM. CONCLUSIONS Our findings do not support a therapeutic
      effect of wrinkling the skin with elastic tape application as a technique to
      increase local blood flow.

PMID- 29332102
TI  - Saudi Medical Journal 2017.
AB  - [No Abstract Available].

PMID- 29332100
TI  - Robot-Assisted Radical Prostatectomy Is More Beneficial for Prostate Cancer
      Patients: A System Review and Meta-Analysis.
AB  - BACKGROUND Robot-assisted radical prostatectomy (RARP) is increasingly used
      worldwide, but comparisons of perioperative, functional, and oncologic outcomes
      among RARP, laparoscopic radical prostatectomy (LRP), and open radical
      prostatectomy (ORP) remain inconsistent. MATERIAL AND METHODS Systematic
      literature searches were conducted using EMBASE, PubMed, the Cochrane Library,
      CNKI, and Science Direct/Elsevier up to April 2017. A meta-analysis was conducted
      using Review Manager and Stata software. RESULTS We included 33 studies. Meta
      analysis revealed that blood loss, transfusion rate, and positive surgical margin
      (PSM) rate were significantly lower following RARP compared with LRP (SMD (95%
      confidence interval [CI]) 0.31 [0.01, 0.61]; combined ORs (95% CI) 5.32 [1.29,
      21.98]; 1.27 [1.10, 1.46]) and ORP (SMD (95% CI) 0.75 [0.30, 1.21]; and combined
      ORs (95% CI) 3.44 [1.21, 9.79]); positive surgical margin (PSM) rates were
      significantly lower following RARP compared with LRP (combined ORs (95% CI) 1.27
      [1.10, 1.46]), but not ORP. Operation time was also shorter for RARP than for
      LRP. The rates of nerve-sparing, recovery of complete urinary continence, and
      recovery of erectile function were significantly higher following RARP compared
      with LRP (combined ORs (95% CI) 0.55 [0.31, 0.95]; 0.66 [0.55, 0.78]; 0.46 [0.30,
      0.71]) and ORP (combined ORs (95% CI) 0.36 [0.21, 0.63]; 0.33 [0.15, 0.74]; 0.65
      [0.37, 1.14]). CONCLUSIONS This meta-analysis demonstrates that RARP results in
      better overall outcomes than LRP and ORP in terms of blood loss, transfusion
      rate, nerve sparing, urinary continence and erectile dysfunction recovery, and
      suggests that RARP offers better results than LRP and ORP in treatment of
      prostate cancer. However, studies with larger sample sizes and long-term results
      are needed.

PMID- 29332103
TI  - Proteomic effects of wet cupping (Al-hijamah).
AB  - Wet cupping (Al-hijamah) is a therapeutic technique practiced worldwide as a part
      of the Unani system of medicine. It involves bloodletting from acupoints on a
      patient's skin to produce a therapeutic outcome. A thorough review of research
      articles on wet cupping with relevance to proteomics field that are indexed by
      Google Scholar, PubMed, and/or Science Direct databases was performed. Eight
      original research articles were summarized in this paper. Overall, wet cupping
      did not have a significant effect on C-reactive protein, Hsp-27, sister chromatid
      exchanges, and cell replication index. In contrast, wet cupping was found to
      produce higher oxygen saturation, eliminate lactate from subcutaneous tissues,
      remove blood containing higher levels of malondialdehyde and nitric oxide, and
      produce higher activity of myeloperoxidase. The proteomic effects of wet cupping
      therapy have not been adequately investigated. Thus, future studies on wet
      cupping that use systemic and sound protocols to avoid bias should be conducted.

PMID- 29332104
TI  - Assessment of the fit of removable partial denture fabricated by computer-aided
      designing/computer aided manufacturing technology.
AB  - OBJECTIVE: To assess the level of evidence that supports the quality of fit for
      removable partial denture (RPD) fabricated by computer-aided designing/computer
      aided manufacturing (CAD/CAM) and rapid prototyping (RP) technology. Methods: An
      electronic search was performed in Google Scholar, PubMed, and Cochrane library
      search engines, using Boolean operators. All articles published in English and
      published in the period from 1950 until April 2017 were eligible to be included
      in this review. The total number of articles contained the search terms in any
      part of the article (including titles, abstracts, or article texts) were
      screened, which resulted in 214 articles. After exclusion of irrelevant and
      duplicated articles, 12 papers were included in this systematic review.  Results:
      All the included studies were case reports, except one study, which was a case
      series that recruited 10 study participants. The visual and tactile examination
      in the cast or clinically in the patient's mouth was the most-used method for
      assessment of the fit of RPDs. From all included studies, only one has assessed
      the internal fit between RPDs and oral tissues using silicone registration
      material. The vast majority of included studies found that the fit of RPDs ranged
      from satisfactory to excellent fit. Conclusion: Despite the lack of clinical
      trials that provide strong evidence, the available evidence supported the claim
      of good fit of RPDs fabricated by new technologies using CAD/CAM.

PMID- 29332105
TI  - The emergence of carbapenem-resistant Klebsiella pneumoniae isolates producing
      OXA-48 and NDM in the Southern (Asir) province, Saudi Arabia.
AB  - OBJECTIVES: To identify the prevalence of carbapenem-resistant Klebsiella
      pneumoniae (CRKP) and the most common types of cabapenemases among CRKP in the
      Southern (Asir) province hospitals, Saudi Arabia. Methods: The cross-sectional
      study was conducted between late April and September in 2015. A total of 54
      Klebsiella pneumoniae (K. pneumoniae) isolates with reduced sensitivity to
      carbapenems were obtained from various clinical specimens of the 2 largest
      hospitals in the Southern province. Minimum inhibitory concentrations (MICs) of
      carbapenems were confirmed using E-test. Molecular detection of the most common
      carbapenemase genes (blaIMP, bla-carbapenem-hydrolyzing oxacillinase [OXA-48],
      blaVIM, bla-New Delhi metallo-beta-lactamas [NDM], and blaKPC) was performed
      using multiplex-polymerase chain reaction. Results: The current study found that
      increasing age and intensive care unit admission were associated with CRKP
      isolation. The major type of carbapenemases was OXA-48 with 81.5% (n=44) and it
      seems to reach an endemic level. New Delhi metallo-beta-lactamas (NDM) was the
      second most frequent carbapenemase by 7.4% (n=4) of isolates while Verona
      integron-encoded metallo-beta-lactamase (VIM) was reported only in one isolate.
      Conclusion: Saudi Arabia receives large numbers of visitors and migrant workers
      from OXA-48 and NDM endemic countries such as Turkey, India, and Pakistan every
      year.

PMID- 29332106
TI  - Single-center experience in the surgical treatment of combined lung
      Echinococcosis.
AB  - OBJECTIVES: To compare results of surgical treatment and complications of
      patients with unilateral or bilateral thoracic and combined pulmonary
      echinococcosis. METHODS: This cross-sectional analysis of a prospective study was
      conducted in the Department of Thoracic and Pediatric Surgery, Scientific Center
      of Surgery, Almaty, Kazakhstan among 598 patients with pulmonary echinococcosis,
      who had surgical treatment with various surgical methods, depending on the
      prevalence of echinococcosis, as follows: right lung in 357 (59.5%) patients,
      left lung in 243 (40.5%) patients, bilateral in 95 (15.8%) patients, and
      complicated echinococcosis in 317 (52.8%) patients. Length of stay per hospital
      stay has been decreased (p less than 0.0001) by video-thoracoscopic
      echinococcectomy with the high-energy laser (HEL) treatment of cyst, than after
      echinococcectomy by cyst treatment with povidone-iodine. Treatment with formalin
      presented the most longest hospital stay (p less than 0.0001). RESULTS:
      Comparative analysis of patients with uncomplicated and complicated pulmonary
      echinococcosis showed a high frequency of postoperative complications associated
      with complicated echinococcosis (OR = 2.2, p less than 0.0001). Conclusion:
      Despite the success of surgical treatment of pulmonary echinococcosis, issues of
      intraoperative dissemination and safety remain, and treatment success rates can
      be improved. These factors require further prospective multicenter studies.

PMID- 29332107
TI  - The sleep architecture of Saudi Arabian patients with Kleine-Levin syndrome.
AB  - OBJECTIVES: To establish baseline sleep architecture during an acute attack of
      Kleine-Levin syndrome (KLS) in a cohort of Saudi Arabian KLS patients and compare
      these characteristics with other published cohorts. Methods: This was a
      retrospective cohort study of the polysomnographic characteristics of 10 typical
      symptomatic Saudi Arabian KLS patients attending the University Sleep Disorders
      Center, King Saud University, Riyadh, Saudi Arabia between 2002 and 2015. Data
      were captured by nocturnal polysomnography during an acute attack of hypersomnia
      and compared with other published cohorts identified via a systematic literature
      search.  Results: Self-reported time asleep during episodes (11.1+/-6.7 hours)
      and recorded total sleep time (TST) (322.5+/-108.7 minutes) were generally
      shorter than other published cohorts. Sleep efficiency was poor at 75.0%+/-25.1%,
      with low relative amounts of rapid eye movement (REM) sleep (16.5+/-5.9% of TST)
      and deep non-REM sleep (stage N3; 10.5+/-6.0% of TST) and high relative amounts
      of non-REM sleep (stage N1; 7.0+/-4.3% of TST). The sleep architecture of Saudi
      Arabian KLS patients was similar to other published cohorts.  Conclusions: Sleep
      architecture of our cohort was relatively normal and broadly similar to other
      published studies, the main features being low sleep efficiency and low relative
      amounts of REM and stage N3 sleep. Time-course polysomnography studies with
      functional imaging may be useful to further establish the exact pathophysiology
      of this disease.

PMID- 29332108
TI  - Impact of body mass index on high blood pressure among obese children in the
      western region of Saudi Arabia.
AB  - OBJECTIVES: To evaluate the impact of body mass index (BMI) on high blood
      pressure among obese children and adolescents in western region, Saudi Arabia. 
      Methods: Cross-sectional data were obtained from 306 (female: 140, male: 166)
      child, between August 2016 and March 2017. A questioner was filled by health
      professionals at ambulatory pediatric clinic followed by waist-hip circumference,
      height, weight, and blood pressure measurement. Diastolic blood pressure (DBP)
      and systolic blood pressure (SBP) were adjusted to gender, height, and age. World
      Health Organization growth standards were used to calculate BMI z-scores.
      Results: The mean age of subjects was 10.1 years. Body mass index increased SBP
      by 1.722 mmHg (p=0.001), and DBP by 0.901 mmHg (p=0.006) in boys, and 0.969 mmHg
      (p=0.036), and DBP by 0.704 mmHg (p=0.045) in girls. Waist hip ratio showed
      significant difference p=0.041, (p=0.0001) between male and female. Of the
      baseline characteristics, age greater than 11 years showed significant
      difference. Symptomatic manifestation of high blood pressure, family history of
      hypertension, level of activity, income level and post-secondary education in
      parents, did not show any significant results. Conclusion: Elevated BMI is
      associated with significantly increased diastolic and systolic blood pressure in
      obese children, especially in children older than 11 years.

PMID- 29332109
TI  - Prevalence of attention deficit hyperactivity disorder and comorbid psychiatric
      and behavioral problems among primary school students in western Saudi Arabia.
AB  - OBJECTIVES: To determine the prevalence of attention deficit hyperactivity
      disorder (ADHD), subtypes of ADHD, and psychiatric, academic, and behavioral
      comorbidity in public primary school students in Jeddah, Saudi Arabia.  Methods:
      This is a cross-sectional study. A simple random sample of 6 primary government
      schools in Jeddah, Saudi Arabia, was identified (3 male, 3 female), and a random
      sample of classes in each of grades 1-6 were selected. Between July and November
      2016, teachers in these classes were asked to complete the Vanderbilt ADHD scale
      on all students in their classes.  Results: A total of 929 students were
      screened. The overall prevalence of ADHD was 5% (5.3% in girls, 4.7% in boys).
      The most prevalent subtype of ADHD was combined type (2.7%), followed by
      hyperactive type (1.2%), and inattentive type (1.1%). The highest prevalence of
      ADHD overall was in grade 3 (7.1%) and the lowest prevalence in grade 6 (3.4%).
      Among students with ADHD, prevalence of comorbid psychiatric, academic, and
      behavioral problems was widespread (56.5% oppositional defiant disorder/conduct
      disorder, 54.4% impaired academic performance, 44.4% classroom behavioral
      problems, 41.3% depression/anxiety). Comorbid problems were especially prevalent
      in combined ADHD subtype and in boys. Conclusions: Attention deficit
      hyperactivity disorder is common in primary school children in Jeddah, and is
      associated with widespread psychiatric, academic, and behavioral problems,
      especially in boys. These findings have implications for the diagnosis and
      treatment of this serious neurobehavioral disorder.

PMID- 29332111
TI  - Prevalence of menstrual problems and their association with psychological stress
      in young female students studying health sciences.
AB  - OBJECTIVES: To identify the prevalence of various menstrual problems in young
      females studying health sciences and to identify their association with academic
      stress. Methods: This was a cross-sectional study, conducted in the health
      colleges of Immam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia between
      February 2015 and February 2016. Seven hundred and thirty-eight female students
      aged 18-25 years anonymously completed menstrual problem identification and
      perceived stress scale questionnaire. The data was analyzed using the Statistical
      Package for Social Sciences version 16.0.  Results: Ninety-one percent of the
      students were suffering from some kind of menstrual problem. The different
      menstrual problems reported, and their incidences included irregular menstruation
      (27%), abnormal vaginal bleeding (9.3%), amenorrhea (9.2%),  menorrhagia (3.4%),
      dysmenorrhea (89.7%), and premenstrual symptoms (46.7%). High perceived stress
      (HPS) was identified in 39% of the students. A significant positive correlation
      was found between HPS and menstrual problems. Students with HPS had 4 times, 2
      times, and 2.8 times increased odds ratio for experiencing amenorrhea,
      dysmenorrhea, and premenstrual syndrome (p less than 0.05).  Conclusion: The most
      prevalent menstrual problems (dysmenorrhea and premenstrual symptoms) in the
      target population were strongly associated with stress. Therefore, it is
      recommended that health science students should be provided with early
      psychological and gynecological counselling to prevent future complications.

PMID- 29332110
TI  - Association of psychological stress with skin symptoms among medical students.
AB  - OBJECTIVES: To evaluate the association between psychological stress and skin
      symptoms among medical students.  Methods: A cross-sectional study was carried
      out between January and June 2015. Electronic survey consists of Perceived Stress
      Questionnaire (PSQ) and Self-Reported Skin Complaints Questionnaire were
      distributed to all 1435 undergraduate students at College of Medicine, King Saud
      University (KSU), Riyadh, Saudi Arabia. Results: Final analysis was performed on
      data from 529 (36.9%) students. Students were divided into three groups: least
      stressed students, n=135, PSQ index less than 0.39; highly stressed students,
      n=136, PSQ index greater than 0.61; and moderately stressed students, n=258.
      Older age, female gender, during exam weeks, and fourth and fifth years of
      medical school (all p less than 0.01) were associated with the highest perceived
      stress levels. When compared to least stressed students, highly stressed students
      suffered from more oily, waxy patches or flakes on scalp (p<=0.0001), dry/sore
      rash (p<=0.0001), warts (p<=0.0001), pimples (p<=0.0001), itchy skin (p<=0.0001),
      hands itchy rash (p<=0.0001), hair loss (p<=0.0001), pull-out own hair (p=0.008),
      scaly skin (p=0.012), troublesome sweating (p=0.016), nails biting (p=0.028), and
      other rashes on face (p= 0.028).  Conclusion: Various common skin conditions
      could appear in context of psychological stress among medical students.

PMID- 29332112
TI  - Evaluation of effectiveness of peer education on smoking behavior among high
      school students.
AB  - OBJECTIVES: To evaluate the effectiveness of peer education on changing the
      smoking behavior of high schoolage children's.  Methods: In this interventional
      study; transtheoretical model, which is one of the cognitive-behavioral models
      was used for application of the peer education. Study was conducted in Izmir
      during 2011-2012 education period and included 338 students from 2 high schools
      The independent variable of the study is peer training.  Descriptive variables
      for a student are age, gender, tendecy of friends to smoke inside and outside the
      school,  the age they have first experienced the habit,  reasons for nicotine
      consumption,  levels of addiction,  chatting about smoking and related harms.
      Family descriptive variables are education level of parents and whether their
      smoking tendency is present or not. Results: Approximately 18.3% of the students
      were current smoker. A positive behavioral change of smoking quitting among
      smoker students was observed after peer education. The number of students in
      precontemplation stage was reduced while the number of students in stages of
      preparation/determination  action and maintenance was increased.  Conclusion:
      Peer education was observed to be an effective  method in the behavioral change
      of smoking teens. Authors strongly suggest peer education to be one of the
      preferred tools in changing the teen behavior in use of  tobacco.

PMID- 29332113
TI  - Changes in the temporomandibular joint disc and temporal and masseter muscles
      secondary to bruxism in Turkish patients.
AB  - OBJECTIVES: To analyze the relationships between temporalis and masseter muscle
      hypertrophy and temporomandibular joint (TMJ) disc displacement in patients with
      severe bruxism using magnetic resonance imaging (MRI). Methods: This
      retrospective study included 100 patients with severe bruxism, referred to the
      Department of Oral and Maxillofacial Surgery, University of Marmara and Istanbul
      Medipol University, Istanbul, Turkey, between January 2015 and December 2016.
      Patients underwent TMJ MRI with a 1.5-T system in open and closed mouth
      positions. The masseter and temporalis muscles were measured in the axial plane
      when the patient's mouth was closed. Results: At its thinnest, the disc averaged
      was 1.11+/-0.24 mm. At their thickest, the masseter averaged was 13.65+/-2.19 mm
      and temporalis muscles was 12.98+/-2.4 mm. Of the discs, 24% were positioned
      normally, 74% were positioned anteriorly, and 2% were positioned posteriorly. The
      temporalis muscle was significantly thicker in patients with normally positioned
      discs than in those with anteriorly positioned discs (p=0.035). Conclusions: The
      temporalis muscle was significantly thicker in patients with normally positioned
      discs than in those with anteriorly positioned discs (p=0.035). Additional
      studies should be conducted to evaluate the relationships between all masticatory
      and surrounding muscles and disc movements in patients with bruxism.

PMID- 29332114
TI  - Dental arch dimensions, form and tooth size ratio among a Saudi sample.
AB  - OBJECTIVES: To determine the dental arch dimensions and arch forms in a sample of
      Saudi orthodontic patients, to investigate the prevalence of Bolton anterior and
      overall tooth size discrepancies, and to compare the effect of gender on the
      measured parameters. Methods: This study is a biometric analysis of dental casts
      of 149 young adults recruited from different orthodontic centers in Jeddah, Saudi
      Arabia. The dental arch dimensions were measured. The measured parameters were
      arch length, arch width, Bolton's ratio, and arch form. The data were analyzed
      using IBM SPSS software version 22.0 (IBM Corporation, New York, USA); this cross
      sectional study was conducted between April 2015 and May 2016. Results: Dental
      arch measurements, including inter-canine and inter-molar distance, were found to
      be significantly greater in males than females (p less than 0.05). The most
      prevalent dental arch forms were narrow tapered (50.3%) and narrow ovoid (34.2%),
      respectively. The prevalence of tooth size discrepancy in all cases was 43.6% for
      anterior ratio and 24.8% for overall ratio. The mean Bolton's anterior ratio in
      all malocclusion classes was 79.81%, whereas the mean Bolton's overall ratio was
      92.21%. There was no significant difference between males and females regarding
      Bolton's ratio. Conclusion: The most prevalent arch form was narrow tapered,
      followed by narrow ovoid. Males generally had larger dental arch measurements
      than females, and the prevalence of tooth size discrepancy was more in Bolton's
      anterior teeth ratio than in overall ratio.

PMID- 29332115
TI  - Ultrasound guided transversus abdominis plane block. Postoperative analgesia in
      children with spinal dysraphism.
AB  - Pediatric regional anesthesia is widely used to relieve postoperative pain after
      abdominal surgery. Commonly used techniques of regional anesthesia include lumbar
      epidural and caudal block. However, the use of central neuraxial blockade has
      limitations. It is contraindicated in patients with clotting abnormalities,
      spinal dysraphism with tethered cord syndrome, meningomyelocele, and following
      spinal surgery with instrumentation. Ultrasound guided transversus abdominis
      plane block is a new method of regional anesthesia that can be used in settings
      where central neuraxial blockade is contraindicated. In this study, we present 5
      pediatric cases in which major abdominal surgery was performed but central
      neuraxial blockade could not be carried out due to spinal abnormalities.

PMID- 29332116
TI  - Applying preventive measures leading to significant reduction of catheter
      associated urinary tract infections in adult intensive care unit.
AB  - OBJECTIVES: To determine the impact of applying the best available clinical
      evidence on the preventive measures to reduce the rate of catheter-associated
      urinary tract infections (CAUTI) in adult intensive care units (ICU).    
      Methods:  Data were collected from adult ICUs (28 beds) from 2008 to 2016. The
      proper use of silicon catheter, aseptic insertion technique, emptying bag three
      fourth via close circuit, the use of appropriate size catheter, securing the
      draining tube on the thigh to keep catheter bag below patient's bladder level and
      removal of the catheter as early as possible were ensured in all patients.  
      Results: Rate of UTI and urinary catheter utilization ratios were reviewed during
      the study period. There was a mean of 6,175 catheter days/year for ICU. Despite
      the overall rise in the urinary catheterization ratio over these years; we
      observed a significant reduction in the UTI rate per 1000 Urinary catheter days;
      from 2.3 in 2010 to 0.3 in 2011 and it was sustained through 2016.  Conclusion:
      The monthly rates of CAUTI significantly declined after the enforcement of agreed
      strategies and interventions to prevent CAUTI rates in adult ICU.

PMID- 29332117
TI  - Pseudocholinesterase levels in patients under electroconvulsive therapy.
AB  - OBJECTIVES: In this study, we aimed to retrospectively assess the correlation of
      pseudocholinesterase (PChE) levels with age, gender, body weight and diagnosed
      psychiatric diseases in electroconvulsive therapy (ECT) cases. Methods: This
      retrospective study was conducted at Bulent Ecevit University Hospital,
      Zonguldak, Turkey, between 2007 and 2011. In the study, 193 ECT case files were
      retrospectively scanned to evaluate PChE values before ECT and other file
      information.  Results: There was no difference between gender in terms of PChE
      levels. Correlation analysis determined a weakly positive correlation between age
      (p=0.013; correlation coefficient [cc]: 0.178) and body weight (p less than
      0.001; cc: 0.273) and PChE levels. No correlation was found between age, gender,
      weight or psychiatric diagnosis, and PChE levels.  Conclusion: Neuromuscular
      blockage is a significant factor that increases patient safety, while increasing
      the efficacy of ECT. In choosing muscle relaxant agents, both patient factors and
      the pharmacological properties of the neuromuscular blocker should be considered.
      We think that in situations with delayed recovery of ECT cases without identified
      PChE levels, low PChE levels must be considered.

PMID- 29332118
TI  - Primary extraskeletal mesenchymal chondrosarcoma arising from the iliac vein.
AB  - [No Abstract Available].

PMID- 29332119
TI  - Autofluorescence of Skin Advanced Glycation End Products as a Risk Factor for
      Open Angle Glaucoma: The ALIENOR Study.
AB  - Purpose: To analyze the association between skin autofluorescence (sAF),
      estimating tissue accumulation of advanced glycation end-products (AGEs), and
      open angle glaucoma (OAG) in an elderly population. Methods: The Antioxydants,
      Lipides Essentiels, Nutrition and maladies OculaiRes (ALIENOR) study is an on
      going epidemiologic population-based study on age-related eye diseases. In 2009
      to 2010, 624 subjects, aged 74 years or older, were recruited. All subjects
      underwent a complete eye examination, including optic disc color photography and
      spectral-domain optical coherence tomography (SD-OCT) examination.
      Sociodemographic and medical history data were collected using standardized
      questionnaires. Glaucoma diagnosis was made using optic nerve head
      retinophotography and International Society for Epidemiologic and Geographical
      Ophthalmology criteria. sAF was measured with a noninvasive autofluorescence
      reader in 467 subjects. Results: Of subjects, 455 had complete data, 424 were
      classified as controls, and 31 classified as OAG. Mean age was 82.3 +/- 4.3
      years, mean and median sAF were 2.8 +/- 0.7 and 2.7 arbitrary units (AU),
      respectively. In a multivariate analysis, higher sAF values (>=2.7 AU) were
      associated with OAG (odds ratio [OR] = 2.28, 95% Confidence Interval [CI]: 1.03;
      5.04). Other variables significantly associated with OAG were age (OR = 1.10,
      95%CI: 1.00; 1.21), glaucoma family history (OR = 2.83, 95%CI: 1.14; 7.01) and
      smoking (1-20 pack-years [OR = 3.31, 95%CI: 1.18; 9.26]; >=20 pack-years [OR =
      3.85, 95%CI: 1.42; 10.46]). Conclusions: Higher level of sAF, which may act as a
      long-term biomarker of metabolic memory, and smoking are independently associated
      with an increased risk of glaucoma. Long-term accumulation of AGEs, a marker of
      oxidative stress, could play a role in the pathogenesis of glaucomatous chronic
      optic neuropathy.

PMID- 29332121
TI  - Pattern Onset ERGs and VEPs Produced by Patterns Arising From Light Increment and
      Decrement.
AB  - Purpose: Our aim was to elaborate how on and off signals contribute to pattern
      ERGs and pattern visual evoked potentials (VEPs) by using pedestal patterns
      arising from incremental and decremental onset stimulation. Methods: Pattern
      onset/offset ERGs and VEPs were produced by black and white checks of 60' side
      length and 88% spatial contrast appearing in a 16 degrees  field for 200 ms from
      white (110 cd/m2), black (7 cd/m2), and gray (48 cd/m2) backgrounds and
      disappeared for 1000 ms. Twenty healthy subjects participated in the study
      (median age 19.5, range, 5-31 years), 10 of whom also underwent pattern
      onset/offset ERG recordings to the same stimuli (median age 25.7, range, 22-31
      years). VEPs were recorded from an occipital array referred to Fz. Pattern
      electroretinograms (PERGs) were recorded from "Dawson-Trick-Litzkow" (DTL) plus
      corneal electrodes referred to ipsilateral outer canthi. Results: There was high
      correlation within subjects of the VEP waveform produced by patterns arising from
      light increment and decrement (group mean correlation coefficient of PVEPs to
      check appearance from black versus white: 87%). An average of increment and
      decrement PERGs simulated the onset PERG from a gray background. This waveform is
      akin to standard International Society for Clinical Electrophysiology of Vision
      (ISCEV) clinical PERGs to reversing checks. Conclusions: In healthy individuals,
      the early components of the pattern onset/offset VEP waveforms are comparable to
      light increment and decrement pedestal stimulation. Pattern onset/offset ERGs to
      pedestal stimulation may be used to probe simultaneous recording of ERGs with
      VEPs in order to obtain an assessment of retinal ganglion cell and optic pathway
      function in patients with less stable fixation.

PMID- 29332120
TI  - Severe Loss of Tritan Color Discrimination in RPE65 Associated Leber Congenital
      Amaurosis.
AB  - Purpose: RPE65-associated Leber congenital amaurosis (RPE65-LCA) is a progressive
      severe retinal dystrophy with early profound dysfunction of rod photoreceptors
      followed by progressive cone photoreceptor degeneration. We aim to provide
      detailed information about how cone dysfunction affects color discrimination.
      Methods: Seven adults (aged 16-21) with RPE65-LCA underwent monocular color
      discrimination assessment using the Trivector and Ellipse versions of three
      computerized tests: Cambridge Colour Test (CCT), low vision version of the
      Cambridge Colour Test (lvvCCT), and the Universal Colour Discrimination Test
      (UCDT). For comparison, subjects were also tested using the American Optical
      Hardy Rand Rittler (AO-HRR) plates. Each assessment was repeated three times.
      Results: The Trivector version of the tests demonstrated that color
      discrimination along the tritan axis was undetectable in four subjects, and
      severely reduced in three subjects. These findings were confirmed by the Ellipse
      version of the tests. Color discrimination along the protan and deutan axes was
      evident but reduced in six of seven subjects. Four of seven subjects were unable
      to read any of the HRR plates. Conclusions: The computerized color vision tests
      adopted in this study provide detailed information about color discrimination in
      adult RPE65-LCA patients. The condition is associated with severe impairment of
      color discrimination, particularly along the tritan axis indicating possible
      early involvement of S-cones, with additional protan and deutan loss to a lesser
      extent. This psychophysical assessment strategy is likely to be valuable in
      measuring the impact of therapeutic intervention on cone function.

PMID- 29332122
TI  - Quantitative Study of the Macular Microvasculature in Human Donor Eyes.
AB  - Purpose: To precisely quantify the macular microvasculature density using
      microperfusion and labeling techniques in human donor eyes. Such information may
      be useful in understanding the role of the macular microvasculature in coping
      with the metabolic requirements of the neurons in this densely packed region, and
      provide a reference point for clinical studies using recently developed optical
      imaging techniques. Methods: The macular microvasculature was perfusion-labeled
      in 18 human donor eyes and optical stacks collected from regions superior,
      temporal, inferior, and nasal to the foveola using confocal microscopy. The
      optical slices were separated into the deep macula vascular layer (DL), and the
      superficial layer (SL) in which all the vessels superficial to the deep macular
      vessel layer were included. The DL and SL images were analyzed and vessel density
      measured according to their orientation from the foveola and in foveal and
      parafoveal regions. Vessel densities were compared across regions and age groups.
      Results: Both the SL and DL showed an increase in vessel density with increasing
      eccentricity from the foveal to parafoveal regions. Vessel density was found to
      rank in the order of inferior > superior > temporal > nasal in both SL and DL
      layers. The SL vascular density was approximately 31%, whereas DL was
      approximately 17%. The DL was planar in nature and density not affected by age.
      Age-related increase in vessel density was observed in the SL. Conclusions:
      Microperfusion and labeling techniques in combination with confocal microscopy
      has enabled collection of reliable data on vascular density in the macula region.
      Regional differences may reflect well-matched vascular supply and neuronal
      demands. Age-related changes might indicate the importance of stable blood supply
      for the human macula.

PMID- 29332123
TI  - BRAF, NRAS, and GNAQ Mutations in Conjunctival Melanocytic Nevi.
AB  - Purpose: To evaluate BRAF, NRAS, and GNAQ mutations in surgical specimens of
      common and blue conjunctival melanocytic nevi. Methods: Surgical specimens from
      25 conjunctival melanocytic nevi (23 common and 2 blue) of 25 patients were
      evaluated. All common nevi were analyzed immunohistochemically for the expression
      of BRAF V600E or NRAS Q61R. One lesion with negative immunoreactivity and for all
      blue nevi, a hybridization capture-based next-generation sequencing method was
      employed for mutation analysis. For common nevi, genetic features were compared
      with clinical and histopathologic findings. Continuous variables (age at excision
      and largest basal diameter) were compared with a Students's t-test and all
      categoric variables were compared with Fisher's Exact Test. Results: Of common
      melanocytic nevi, 9 (39.1%) were immunoreactive for NRASQ61R and 13 (56.5%) were
      immunoreactive for BRAFV600E. One common nevus, which was immunonegative for both
      BRAFV600E and NRASQ61R was found to harbor an NRASQ61K mutation by sequence
      analysis. Patients with NRAS-mutated nevi were more likely to report occurrence
      of the lesion prior to 18-years old and more likely to have intrinsic cysts. The
      mean largest basal diameter was 6.0 and 3.5 mm for NRAS- and BRAF-immunoreactive
      lesions, respectively (P = 0.003). GNAQ mutations were identified in each of the
      two blue nevi of this study. Conclusions: These findings document that common
      conjunctival melanocytic nevi have mutually exclusive mutations in BRAF and NRAS.
      The two conjunctival blue nevi harbored GNAQ mutations. This suggests the driver
      mutations of conjunctival nevi are similar to those of nevi of the skin. At the
      molecular level, conjunctival nevi appear more like cutaneous nevi than choroidal
      nevi.

PMID- 29332124
TI  - Optimal Audiovisual Integration in the Ventriloquism Effect But Pervasive
      Deficits in Unisensory Spatial Localization in Amblyopia.
AB  - Purpose: Classically understood as a deficit in spatial vision, amblyopia is
      increasingly recognized to also impair audiovisual multisensory processing.
      Studies to date, however, have not determined whether the audiovisual
      abnormalities reflect a failure of multisensory integration, or an optimal
      strategy in the face of unisensory impairment. We use the ventriloquism effect
      and the maximum-likelihood estimation (MLE) model of optimal integration to
      investigate integration of audiovisual spatial information in amblyopia. Methods:
      Participants with unilateral amblyopia (n = 14; mean age 28.8 years; 7
      anisometropic, 3 strabismic, 4 mixed mechanism) and visually normal controls (n =
      16, mean age 29.2 years) localized brief unimodal auditory, unimodal visual, and
      bimodal (audiovisual) stimuli during binocular viewing using a location
      discrimination task. A subset of bimodal trials involved the ventriloquism
      effect, an illusion in which auditory and visual stimuli originating from
      different locations are perceived as originating from a single location.
      Localization precision and bias were determined by psychometric curve fitting,
      and the observed parameters were compared with predictions from the MLE model.
      Results: Spatial localization precision was significantly reduced in the
      amblyopia group compared with the control group for unimodal visual, unimodal
      auditory, and bimodal stimuli. Analyses of localization precision and bias for
      bimodal stimuli showed no significant deviations from the MLE model in either the
      amblyopia group or the control group. Conclusions: Despite pervasive deficits in
      localization precision for visual, auditory, and audiovisual stimuli, audiovisual
      integration remains intact and optimal in unilateral amblyopia.

PMID- 29332126
TI  - Erratum.

PMID- 29332127
TI  - Proteome Profiling of Developing Murine Lens Through Mass Spectrometry.
AB  - Purpose: We previously completed a comprehensive profile of the mouse lens
      transcriptome. Here, we investigate the proteome of the mouse lens through mass
      spectrometry-based protein sequencing at the same embryonic and postnatal time
      points. Methods: We extracted mouse lenses at embryonic day 15 (E15) and 18 (E18)
      and postnatal day 0 (P0), 3 (P3), 6 (P6), and 9 (P9). The lenses from each time
      point were preserved in three distinct pools to serve as biological replicates
      for each developmental stage. The total cellular protein was extracted from the
      lens, digested with trypsin, and labeled with isobaric tandem mass tags (TMT) for
      three independent TMT experiments. Results: A total of 5404 proteins were
      identified in the mouse ocular lens in at least one TMT set, 4244 in two, and
      3155 were present in all three TMT sets. The majority of the proteins exhibited
      steady expression at all six developmental time points; nevertheless, we
      identified 39 proteins that exhibited an 8-fold differential (higher or lower)
      expression during the developmental time course compared to their respective
      levels at E15. The lens proteome is composed of diverse proteins that have
      distinct biological properties and functional characteristics, including proteins
      associated with cataractogenesis and autophagy. Conclusions: We have established
      a comprehensive profile of the developing murine lens proteome. This repository
      will be helpful in identifying critical components of lens development and
      processes essential for the maintenance of its transparency.

PMID- 29332128
TI  - Pharmacologic Characterization of Omidenepag Isopropyl, a Novel Selective EP2
      Receptor Agonist, as an Ocular Hypotensive Agent.
AB  - Purpose: The objective of this study was to investigate the pharmacologic
      characteristics of omidenepag isopropyl (OMDI), a compound developed as a novel
      intraocular pressure (IOP)-lowering agent, with better IOP control and fewer side
      effects than other prostanoid receptor agonists such as prostaglandin F receptor
      (FP) agonists. Methods: Binding activities of OMDI and its hydrolyzed form,
      omidenepag (OMD), to human recombinant prostanoid receptors (DP1-2, EP1-4, FP,
      and IP) were evaluated. Based on these binding assays, the agonistic activities
      of OMDI and OMD were further evaluated using cultured cells expressing selected
      prostanoid receptors. The pharmacokinetics of OMDI after topical administration
      was assessed in rabbits by measurement of the concentrations of both OMDI and OMD
      in aqueous humor. The ocular hypotensive effect of OMDI was evaluated in ocular
      normotensive rabbits, dogs, and both ocular normotensive and hypertensive
      monkeys. Results: OMD was determined to be a selective EP2 receptor agonist. OMDI
      weakly bound to EP1; however, the agonistic activity of OMDI to this receptor was
      not demonstrated in the functional assay. After topical administration of OMDI,
      OMD was detected in aqueous humor whereas OMDI was not detectable. OMDI
      significantly lowered IOP in both ocular normotensive and hypertensive animals.
      The significant ocular hypotensive effects of OMDI were demonstrated by both
      single and repeated dosing, and its effective duration suggests sufficient
      efficacy by once-daily dosing. Conclusions: These studies demonstrated that OMDI
      is hydrolyzed in the eye to OMD, an EP2 receptor agonist, with a significant
      ocular hypotensive effect in both ocular normotensive and hypertensive animal
      models.

PMID- 29332125
TI  - ICG-001 Exerts Potent Anticancer Activity Against Uveal Melanoma Cells.
AB  - Purpose: Uveal melanoma (UM) is uniformly refractory to all available systemic
      chemotherapies, thus creating an urgent need for novel therapeutics. In this
      study, we investigated the sensitivity of UM cells to ICG-001, a small molecule
      reported to suppress the Wnt/beta-catenin-mediated transcriptional program.
      Methods: We used a panel of UM cell lines to examine the effects of ICG-001 on
      cellular proliferation, migration, and gene expression. In vivo efficacy of ICG
      001 was evaluated in a UM xenograft model. Results: ICG-001 exerted strong
      antiproliferative activity against UM cells, leading to cell cycle arrest,
      apoptosis, and inhibition of migration. Global gene expression profiling revealed
      strong suppression of genes associated with cell cycle proliferation, DNA
      replication, and G1/S transition. Gene set enrichment analysis revealed that ICG
      001 suppressed Wnt, mTOR, and MAPK signaling. Strikingly, ICG-001 suppressed the
      expression of genes associated with UM aggressiveness, including CDH1, CITED1,
      EMP1, EMP3, SDCBP, and SPARC. Notably, the transcriptomic footprint of ICG-001,
      when applied to a UM patient dataset, was associated with better clinical
      outcome. Lastly, ICG-001 exerted anticancer activity against a UM tumor xenograft
      in mice. Conclusions: Using in vitro and in vivo experiments, we demonstrate that
      ICG-001 has strong anticancer activity against UM cells and suppresses
      transcriptional programs critical for the cancer cell. Our results suggest that
      ICG-001 holds promise and should be examined further as a novel therapeutic agent
      for UM.

PMID- 29332129
TI  - Aspergillus fumigatus Increased PAR-2 Expression and Elevated Proinflammatory
      Cytokines Expression Through the Pathway of PAR-2/ERK1/2 in Cornea.
AB  - Purpose: To determine the role of protease-activated receptor-2 (PAR-2) in cornea
      infected by Aspergillus fumigatus. Methods: PAR-2 was tested in normal and
      infected corneas of C57BL/6 mice. Mice corneas were infected with A. fumigatus
      with or without pretreatment of PAR-2 antagonist (FSLLRY-NH2). Polymorphonuclear
      neutrophilic leukocytes (PMNs) were stimulated with 75% ethanol-killed A.
      fumigatus with or without pretreatment of FSLLRY-NH2. Disease severity was
      documented by clinical score and photographs with a slit lamp. PCR, Western blot,
      and ELISA tested expression of PAR-2, IL-1beta, TNF-alpha, IFN-gamma, MIP-2, and
      p-ERK1/2. PMN infiltration was assessed by myeloperoxidase assay and
      immunofluorescent staining. Results: PAR-2 expression was significantly elevated
      by A. fumigatus, whereas the upregulation was significantly inhibited by FSLLRY
      NH2 in mice corneas. FSLLRY-NH2 decreased disease response, PMN infiltration, and
      proinflammatory cytokine expression compared with infected control. In PMNs, PAR
      2 expression was also significantly increased by A. fumigatus, which was
      significantly inhibited by FSLLRY-NH2. FSLLRY-NH2 significantly inhibited
      proinflammatory cytokine protein expression, as compared with that in infected
      control cells, which may be modified by p-ERK1/2. Conclusions: These data provide
      evidence that A. fumigatus increased PAR-2 expression and elevated disease, PMN
      infiltration, and proinflammatory cytokine expression through PAR-2, which may be
      modified by p-ERK1/2.

PMID- 29332131
TI  - Assessment of Human Corneas Prior to Transplantation Using High-Resolution Two
      Photon Imaging.
AB  - Purpose: The purpose of this study was to evaluate the feasibility of using two
      photon imaging (TPI) to assess the condition of human corneas for
      transplantation. Methods: Human corneas were imaged after different storage
      times: short-term (STS), medium-term (MTS), and long-term (LTS) storage. A high
      resolution, custom-built 5-dimensional multiphoton microscope with 12-fs pulsed
      laser excitation was used for image acquisition. Results: Optical discrimination
      between different corneal layers and sublayers based on their morphologic
      characteristics revealed by two-photon autofluorescence (AF) is possible.
      Furthermore, all layers were characterized based on AF lifetimes to gain
      information on metabolic activities of cells. The NAD(P)H free to protein-bound
      ratio (a1/a2) of epithelial cells increased significantly in both MTS and LTS
      corneas compared with STS corneas. In endothelial cells, NAD(P)H a1/a2 was
      significantly increased in MTS samples. For keratocytes, the NAD(P)H a1/a2
      decreased significantly with storage time. This could indicate that the metabolic
      activity of the epithelial and endothelial cells reduces, whereas the activity of
      keratocytes increases with storage time. The analysis of the stroma SHG images
      indicated that the organization of collagen fibers decreases with storage time.
      The feasibility of measuring the endothelial cell density (ECD) using TPI was
      demonstrated. An ECD of 1461 +/- 190 cells/mm2 was obtained for MTS samples based
      on TPI. Conclusions: TPI can provide information not accessible by current
      clinical methods, such as the cells' metabolic state and structural organization
      of the stroma, with subcellular resolution. Thus, it may improve the screening
      process of corneas prior to transplantation and might help to optimize the
      storage conditions.

PMID- 29332132
TI  - Reply to Zamani and Hassanian-Moghaddam, 2017: being specific and targeting
      disease-causing pathology matter in therapeutics.

PMID- 29332130
TI  - Cerebrospinal Fluid Pressure: Revisiting Factors Influencing Optic Nerve Head
      Biomechanics.
AB  - Purpose: To model the sensitivity of the optic nerve head (ONH) biomechanical
      environment to acute variations in IOP, cerebrospinal fluid pressure (CSFP), and
      central retinal artery blood pressure (BP). Methods: We extended a previously
      published numerical model of the ONH to include 24 factors representing tissue
      anatomy and mechanical properties, all three pressures, and constraints on the
      optic nerve (CON). A total of 8340 models were studied to predict factor
      influences on 98 responses in a two-step process: a fractional factorial
      screening analysis to identify the 16 most influential factors, followed by a
      response surface methodology to predict factor effects in detail. Results: The
      six most influential factors were, in order: IOP, CON, moduli of the sclera,
      lamina cribrosa (LC) and dura, and CSFP. IOP and CSFP affected different aspects
      of ONH biomechanics. The strongest influence of CSFP, more than twice that of
      IOP, was on the rotation of the peripapillary sclera. CSFP had similar influence
      on LC stretch and compression to moduli of sclera and LC. On some ONHs, CSFP
      caused large retrolamina deformations and subarachnoid expansion. CON had a
      strong influence on LC displacement. BP overall influence was 633 times smaller
      than that of IOP. Conclusions: Models predict that IOP and CSFP are the top and
      sixth most influential factors on ONH biomechanics. Different IOP and CSFP
      effects suggest that translaminar pressure difference may not be a good parameter
      to predict biomechanics-related glaucomatous neuropathy. CON may drastically
      affect the responses relating to gross ONH geometry and should be determined
      experimentally.

PMID- 29332134
TI  - Breast cancer survivorship: state of the science.
AB  - PURPOSE: Only recently has breast cancer survivorship earned formal recognition
      as a research discipline. Complicating survivorship research is the frequent
      overlap between aging and treatment sequelae. The ACS/ASCO 2016 Breast Cancer
      Survivorship Care Guideline (Guideline) reflects comprehensive literature review
      through April 2015, while the jointly sponsored, inaugural Cancer Survivorship
      Symposium in 2016 (Symposium) reflects ongoing research activity in the area.
      Together, these platforms provide an opportunity to examine the use of randomized
      trials and controlled studies in survivorship care research. METHODS: All 236
      citations from the Guideline and all 250 abstracts from the Symposium were
      reviewed independently by two authors and assigned to prospectively determined
      categories. RESULTS: Guideline citations were most frequently reviews (n = 88,
      37.3%) and non-randomized, non-controlled studies (n = 51, 21.6%). Thirty-seven
      (15.7%) randomized trials were cited. Only 9% of Guideline recommendations were
      based on randomized clinical trial evidence, while 64% were based on evidence
      level "0" (expert opinion, clinical practice, etc.). Symposium abstracts
      consisted largely of non-randomized, non-controlled studies (n = 113, 45.2%),
      with ten completed randomized trials (4%). Few Guideline citations or Symposium
      abstracts incorporated matched, cancer-free controls. CONCLUSIONS: Based on the
      literature underlying the ASCO Guideline as well as a survey of the Cancer
      Survivorship Symposium abstracts, a significant proportion of the survivorship
      literature at least through 2015 consisted of non-randomized, non-controlled
      studies. To optimally address survivorship issues, cancer therapy sequelae need
      to be distinguished from normal aging in studies incorporating cancer-free
      controls, and randomized clinical trials are needed to inform intervention
      strategies.

PMID- 29332133
TI  - Fumarate hydratase (FH) deficiency in uterine leiomyomas: recognition by
      histological features versus blind immunoscreening.
AB  - Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome is a rare
      autosomal dominant disease caused by germline mutations in the fumarate hydratase
      (FH) gene. Affected individuals develop cutaneous and uterine leiomyomas and
      aggressive RCC. To date, only few publications described the frequency and
      morphology of FH-deficient uterine leiomyomas. We reviewed 22 cases collected
      over 8 years from routine and consultation files based on distinctive
      histological features. In addition, we screened 580 consecutive uterine
      leiomyomas from 484 patients, 23 extra-uterine and 8 uterine leiomyosarcomas, and
      6 leiomyomas with bizarre nuclei for FH loss using immunohistochemistry (IHC) on
      tissue microarrays (TMAs). All 22 FH-deficient cases were suspected on H&E
      sections and confirmed by FH IHC. Patients' ages ranged from 25 to 70 years
      (median 36). Seventeen patients had multiple nodules (2-14) measuring up to 11.8
      cm. None of the patients had stigmata or family history of the HLRCC syndrome.
      Histologically, all FH-deficient tumors showed consistent and reproducible
      features as reported previously. FH loss was detected in 2/534 evaluable
      leiomyomas (0.4%), but in none of leiomyosarcomas. Two of six leiomyomas with
      bizarre nuclei were FH-deficient. FH-deficient uterine leiomyomas are rare in
      routine material (= 0.4%). They can be reliably identified or suspected by
      consistent morphological features. Our data showed predictive morphology to be
      superior to blind IHC screening for detecting them. The relationship of FH
      deficient uterine smooth muscle tumors to the HLRCC syndrome needs further
      clarification.

PMID- 29332136
TI  - Consideration of population and cultural factors in American Indian/Alaskan
      Native (AIAN) research.

PMID- 29332135
TI  - Sequential versus simultaneous use of chemotherapy and gonadotropin-releasing
      hormone agonist (GnRHa) among estrogen receptor (ER)-positive premenopausal
      breast cancer patients: effects on ovarian function, disease-free survival, and
      overall survival.
AB  - OBJECTIVE: To investigate ovarian function and therapeutic efficacy among
      estrogen receptor (ER)-positive, premenopausal breast cancer patients treated
      with gonadotropin-releasing hormone agonist (GnRHa) and chemotherapy
      simultaneously or sequentially. METHOD: This study was a phase 3, open-label,
      parallel, randomized controlled trial (NCT01712893). Two hundred sixteen
      premenopausal patients (under 45 years) diagnosed with invasive ER-positive
      breast cancer were enrolled from July 2009 to May 2013 and randomized at a 1:1
      ratio to receive (neo)adjuvant chemotherapy combined with sequential or
      simultaneous GnRHa treatment. All patients were advised to receive GnRHa for at
      least 2 years. The primary outcome was the incidence of early menopause, defined
      as amenorrhea lasting longer than 12 months after the last chemotherapy or GnRHa
      dose, with postmenopausal or unknown follicle-stimulating hormone and estradiol
      levels. The menstrual resumption period and survivals were the secondary
      endpoints. RESULT: The median follow-up time was 56.9 months (IQR 49.5-72.4
      months). One hundred and eight patients were enrolled in each group. Among them,
      92 and 78 patients had complete primary endpoint data in the sequential and
      simultaneous groups, respectively. The rates of early menopause were 22.8%
      (21/92) in the sequential group and 23.1% (18/78) in the simultaneous group
      [simultaneous vs. sequential: OR 1.01 (95% CI 0.50-2.08); p = 0.969; age-adjusted
      OR 1.13; (95% CI 0.54-2.37); p = 0.737]. The median menstruation resumption
      period was 12.0 (95% CI 9.3-14.7) months and 10.3 (95% CI 8.2-12.4) months for
      the sequential and simultaneous groups, respectively [HR 0.83 (95% CI 0.59-1.16);
      p = 0.274; age-adjusted HR 0.90 (95%CI 0.64-1.27); p = 0.567]. No significant
      differences were evident for disease-free survival (p = 0.290) or overall
      survival (p = 0.514) between the two groups. CONCLUSION: For ER-positive
      premenopausal patients, the sequential use of GnRHa and chemotherapy showed
      ovarian preservation and survival outcomes that were no worse than simultaneous
      use. The application of GnRHa can probably be delayed until menstruation
      resumption after chemotherapy.

PMID- 29332137
TI  - Variation in guideline-concordant care for elderly patients with metastatic
      breast cancer in the United States.
AB  - PURPOSE: Prior studies have identified shortcomings in the quality of care for
      early-stage breast cancer. Guidelines recommend systemic therapy for metastatic
      breast cancer (MBC), but few studies have examined guideline concordance for
      these patients. METHODS: We used Surveillance, Epidemiology, and End Results
      (SEER)-Medicare data to identify patients aged >= 66 diagnosed in 2010-2011 with
      de novo MBC who were continuously enrolled in fee-for-service Medicare. We
      described initial care (within 6 months of diagnosis) for hormone receptor (HR)
      positive/human epidermal receptor-2 (HER2)-negative, HER2-positive, and triple
      negative (TN) tumors. We identified factors independently associated with
      receiving no initial systemic therapy, and compared hospice and hospital
      utilization for treated versus untreated patients. RESULTS: Among 446 patients,
      65% were HR-positive, 21% were HER2-positive, and 14% were TN. Most patients
      (76.9%) received initial systemic treatment. Among treated HR-positive patients,
      15% received chemotherapy as initial treatment; among treated HER2-positive
      patients, 34% did not receive HER2-targeted initial therapy. Factors
      independently associated with receiving no initial systemic therapy included
      older age (ORage continuous/year = 1.08, 95% CI 1.04-1.11), being not married
      (ORnot married vs. married = 2.87, 95% CI 1.42-5.81), and subtype (ORTN vs. HR+ =
      4.95, 95% CI 2.53-9.71). Of patients who did not receive initial systemic
      therapy, 41.1% did not receive hospice services. CONCLUSIONS: In this population
      based MBC cohort, almost one quarter did not receive initial systemic therapy and
      a substantial proportion of treated patients did not receive guideline-concordant
      first-line therapy. Further research should explore underuse of chemotherapy and
      HER2-targeted therapies, investigate whether patterns of care are consistent with
      patient preferences, and identify opportunities to optimize hospice utilization
      for patients not receiving treatment.

PMID- 29332139
TI  - Effect of Host Human Products on Natural Transformation in Acinetobacter
      baumannii.
AB  - Our previous data show that serum albumin can trigger natural transformation in
      Acinetobacter baumannii. However, extracellular matrix/basal membrane components,
      norepinephrine, and mucin did not have a significant effect on this process.
      Therefore, the effect of human products appears to be albumin specific, as both
      BSA and HSA have been shown to increase of natural transformation.

PMID- 29332140
TI  - Identification of Cross Reactive Antigens of C. botulinum Types A, B, E & F by
      Immunoproteomic Approach.
AB  - Diseases triggered by microorganisms can be controlled by vaccines, which need
      neutralizing antigens. Hence, it is very crucial to identify extremely efficient
      immunogens for immune prevention. Botulism, a fatal neuroparalytic disease, is
      caused by botulinum neurotoxins produced by the anaerobic, Gram-positive spore
      forming bacteria, Clostridium botulinum. Food-borne botulism and iatrogenic
      botulism are caused by botulinum toxin. Wound botulism, infant botulism, and
      adult intestinal botulism are caused by primarily C. botulinum followed by
      secondary intoxication. To identify protective antigens, whole cell proteome of
      C. botulinum type B was separated by two-dimensional gel electrophoresis. 2-D gel
      of whole cell proteins was probed with hyper immune sera of whole cell proteins
      of C. botulinum types A, E, and F. Six cross immunoreactive proteins were
      identified. These immunoreactive proteins will be further tested for developing
      vaccines and serodiagnostic markers against botulism.

PMID- 29332142
TI  - Purification and characterization of a novel organic solvent-tolerant and cold
      adapted lipase from Psychrobacter sp. ZY124.
AB  - By screening 25 different psychrophilic strains isolated from the Arctic habitat,
      we isolated a strain capable of producing lipase. We identified this strain as
      Psychrobacter sp. ZY124 based on the amplified 16S rDNA sequence. The lipase,
      named as Lipase ZC12, produced from the supernatant of Psychrobacter sp. ZY124
      cultured at 15  degrees C was purified to homogeneity by ammonium sulfate
      precipitation followed by Phenyl Sepharose FF gel hydrophobic chromatography.
      Based on the obtained amino acid sequence, Lipase ZC12 is classified as a member
      of the Proteus/psychrophilic subfamily of lipase family I.1; it has a molecular
      weight of 37.9 kDa. We also determined that the apparent optimum temperature for
      Lipase ZC12 activity is 40  degrees C. Lipase ZC12 shows remarkable organic
      solvent tolerance by remaining more 50% after incubated with 10-90% different
      organic solvents. In addition, acyl chain esters with C12 or longer were
      confirmed to be preferable substrates for Lipase ZC12. Lipase ZC12 also shows
      better stereoselectivity for (R, S)-1-phenylethanol chiral resolution in n-hexane
      solvent with (S)-1-phenylethanol (eep 92%) and conversion rate (39%) by
      transesterification reactions. These properties may provide potential
      applications in biocatalysis and biotransformation in non-aqueous media, such as
      in detergent, transesterification or esterification and chiral resolution.

PMID- 29332141
TI  - Cultivable fungi present in Antarctic soils: taxonomy, phylogeny, diversity, and
      bioprospecting of antiparasitic and herbicidal metabolites.
AB  - Molecular biology techniques were used to identify 218 fungi from soil samples
      collected from four islands of Antarctica. These consisted of 22 taxa of 15
      different genera belonging to the Zygomycota, Ascomycota, and Basidiomycota.
      Mortierella, Antarctomyces, Pseudogymnoascus, and Penicillium were the most
      frequently isolated genera and Penicillium tardochrysogenum, Penicillium
      verrucosus, Goffeauzyma gilvescens, and Mortierella sp. 2 the most abundant taxa.
      All fungal isolates were cultivated using solid-state fermentation to obtain
      their crude extracts. Pseudogymnoascus destructans, Mortierella parvispora, and
      Penicillium chrysogenum displayed antiparasitic activities, whilst extracts of P.
      destructans, Mortierella amoeboidea, Mortierella sp. 3, and P. tardochrysogenum
      showed herbicidal activities. Reported as pathogenic for bats, different isolates
      of P. destructans exhibited trypanocidal activities and herbicidal activity, and
      may be a source of bioactive molecules to be considered for chemotherapy against
      neglected tropical diseases. The abundant presence of P. destructans in soils of
      the four islands gives evidence supporting that soils in the Antarctic Peninsula
      constitute a natural source of strains of this genus, including some P.
      destructans strains that are phylogenetically close to those that infect bats in
      North America and Europe/Palearctic Asia.

PMID- 29332138
TI  - Pathophysiology of Eosinophilic Esophagitis.
AB  - Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus
      associated with an atopic predisposition which appears to be increasing in
      prevalence over the last few decades. Symptoms stem from fibrosis, swelling, and
      smooth muscle dysfunction. In the past two decades, the etiology of EoE has been
      and is continuing to be revealed. This review provides an overview of the effects
      of genetics, environment, and immune function including discussions that touch on
      microbiome, the role of diet, food allergy, and aeroallergy. The review further
      concentrates on the pathophysiology of the disease with particular focus on the
      important concepts of the molecular etiology of EoE including barrier dysfunction
      and allergic hypersensitivity.

PMID- 29332143
TI  - Conjunction of G-quadruplex and stem-loop in the 5' untranslated region of mouse
      hepatocyte nuclear factor 4-alpha1 mediates strong inhibition of protein
      expression.
AB  - Hepatocyte nuclear factor 4-alpha (HNF4alpha) is a well-established master
      regulator of liver development and function. Restoration of HNF4alpha can treat
      multiple liver disorders and liver cancers. To date, HNF4alpha is still
      "undruggable" due to lack of known activating ligands. Thus, understanding the
      regulatory mechanism of HNF4alpha expression may help develop an alternative
      approach to modulate HNF4alpha protein levels. G-quadruplexes (G4) are non
      canonical stable secondary structures discovered mostly in the promoters of
      oncogenes. Recent genome-wide studies demonstrate the enrichment of G4s in the 5'
      untranslated region (UTR). By protoporphyrin IX-binding assay and circular
      dichroism spectrum, we validated the presence of a chemically highly stable 4
      ring G4 within the 5' UTR of mouse Hnf4a1. Our real-time PCR and Western blot
      data showed that the Hnf4a1 5' UTR caused a remarkable translational suppression
      regardless of a moderate effect on Hnf4a1 mRNA levels. The subsequent
      deletion/mutation analysis of Hnf4a1 5' UTR using dual-luciferase reporter assays
      further demonstrated that although the disruption of the chemically highly stable
      4-ring G4 resulted in a marked attenuation of inhibition, the G4 alone only
      weakly inhibited translation. Likewise, disruption of a long stem-loop adjacent
      to the 4-ring G4 markedly attenuated translational inhibition, although the stem
      loop alone only exerted a weak inhibitory effect. Thus, the tight conjunction of
      G4s and an adjacent stem-loop within the Hnf4a1 5' UTR was both necessary and
      sufficient to mediate the very strong translational repression. Our results
      establish a novel working model that a chemically stable G4 may require co
      factors to be bio-stable for exerting biological functions.

PMID- 29332146
TI  - Mercury Concentrations in Northern Two-Lined Salamanders from Stream Ecosystems
      in Garrett County, Maryland.
AB  - The purpose of this study was to increase our understanding of the
      bioaccumulation of mercury in northern two-lined salamanders (Eurycea bislineata
      bislineata) in freshwater stream ecosystems. We collected 111 adults and 131
      larval northern two-lined salamanders from six streams in Garrett County,
      Maryland. These salamanders were collected in April, July, and September 2010. We
      measured the size and tissue mercury content in all of these salamanders. We also
      measured the total and methyl mercury concentrations in stream water on monthly
      basis from April through December 2010. Averaged over all stream ecosystems,
      adult northern two-lined salamanders had significantly greater total mercury
      concentrations than larval salamanders (29.6 vs. 23.8 ng g-1). For individual
      stream ecosystems, the mean tissue mercury contents in adult northern two-lined
      salamanders were significantly greater than the mean tissue mercury contents in
      larval northern two-lined salamanders for Bear Pen and Mill Run. Adult and larval
      salamanders from the Little Savage River and Mud Lick had 1.5-2 times greater
      mean tissue mercury contents than salamanders in all other streams. These two
      streams also had significantly greater total and methyl mercury concentrations.
      Despite their different life-stage feeding behaviors (terrestrial vs. aquatic),
      the tissue mercury contents of adult (r = 0.76) and larval (r = 0.79) northern
      two-lined salamanders were strongly linked to the methyl mercury concentrations
      in stream water. This implies that northern two-lined salamanders may be a useful
      bioindicator of mercury pollution in relatively pristine stream ecosystems.

PMID- 29332144
TI  - Long-Acting beta2-Agonists in Asthma: Enantioselective Safety Studies are Needed.
AB  - Long-acting beta2-agonists (LABAs) such as formoterol and salmeterol are used for
      prolonged bronchodilatation in asthma, usually in combination with inhaled
      corticosteroids (ICSs). Unexplained paradoxical asthma exacerbations and deaths
      have been associated with LABAs, particularly when used without ICS. LABAs
      clearly demonstrate effective bronchodilatation and steroid-sparing activity, but
      long-term treatment can lead to tolerance of their bronchodilator effects. There
      are also concerns with regard to the effects of LABAs on bronchial
      hyperresponsiveness (BHR), where long-term use is associated with increased BHR
      and loss of bronchoprotection. A complicating factor is that formoterol and
      salmeterol are both chiral compounds, usually administered as 50:50 racemic (rac
      ) mixtures of two enantiomers. The chiral nature of these compounds has been
      largely forgotten in the debate regarding LABA safety and effects on BHR,
      particularly that (S)-enantiomers of beta2-agonists may be deleterious to asthma
      control. LABAs display enantioselective pharmacokinetics and pharmacodynamics.
      Biological plausibility of the deleterious effects of beta2-agonists (S)
      enantiomers is provided by in vitro and in vivo studies from the short-acting
      beta2-agonist (SABA) salbutamol. Supportive clinical findings include the fact
      that patients in emergency departments who demonstrate a blunted response to
      salbutamol are more likely to benefit from (R)-salbutamol than rac-salbutamol,
      and resistance to salbutamol appears to be a contributory mechanism in rapid
      asthma deaths. More effort should therefore be applied to investigating potential
      enantiospecific effects of LABAs on safety, specifically bronchoprotection.
      Safety studies directly assessing the effects of LABA (S)-enantiomers on BHR are
      long overdue.

PMID- 29332145
TI  - The experiences and beliefs of older people in Scottish very sheltered housing
      about using multi-compartment compliance aids.
AB  - Background Multi-compartment compliance aids (MCAs) are promoted as a potential
      solution to medicines non-adherence despite the absence of high quality evidence
      of effectiveness of MCA use impacting medicines adherence or any clinical
      outcomes. Furthermore, there is a lack of qualitative research which focuses on
      the perspectives of older people receiving MCAs. Objectives To describe
      experiences and beliefs surrounding very sheltered housing (VSH) residents' use
      of MCAs with emphasis on issues of personalisation, reablement, shared decision
      making, independence and support. Setting VSH in north east Scotland. Methods
      Qualitative, face-to-face interviews with 20 residents (>= 65 years, using MCA >
      6 months) in three VSH complexes. Interviews focused on: when and why the MCA was
      first introduced; who was involved in making that decision; how the MCA was used;
      perceptions of benefit; and any difficulties encountered. Interviews were
      audiorecorded, transcribed and analysed using a framework approach. Main outcome
      measure Experiences and beliefs surrounding use of MCAs. Results Nine themes were
      identified: shared decision-making; independence; knowledge and awareness of why
      MCA had been commenced; support in medicines taking; knowledge and awareness of
      medicines; competent and capable to manage medicines; social aspects of carers
      supporting MCA use; benefits of MCAs; and drawbacks. Conclusion Experiences and
      beliefs are diverse and highly individual, with themes identified aligning to key
      strategies and policies of the Scottish Government, and other developed countries
      around the world, specifically personalisation shared decision making,
      independence, reablement and support.

PMID- 29332147
TI  - Phosphorus allocation and phosphatase activity in grasses with different growth
      rates.
AB  - Different growth rates of grasses from South American natural grasslands are
      adaptations to soils of low fertility. Grasses with fast growth rate are species
      with an accumulation of nutrients in soluble forms, with a high metabolic rate.
      This work aimed to study whether grasses with different growth rates have
      different phosphorus (P) uptake and efficiency of P use with high and low P
      availability in soil, as well as whether phosphatase activity is related to the
      species growth rate and variations in P biochemical forms in the tissues. Three
      native grasses (Axonopus affinis, Paspalum notatum, and Andropogon lateralis)
      were grown in pots with soil. Along plant growth, biomass production and its
      structural components were measured, as well as leaf acid phosphatase activity
      and leaf P chemical fractions. At 40 days of growth, leaf acid phosphatase
      activity declined by about 20-30% with an increase of P availability in soil for
      A. affinis and P. notatum, respectively. Under both soil P levels, P. notatum
      showed the highest plant total biomass, leaf dry weight and highest P use
      efficiency. A. affinis presented the higher P uptake efficiency and soluble
      organic P concentration in the leaf tissues. A. lateralis showed P-Lipid
      concentration 1.6 and 1.3 times higher than A. affinis and P. notatum,
      respectively. In conclusion, acid phosphatase activity in grass of higher growth
      rate is related to higher remobilization of P due to higher demand, as in A.
      affinis, and higher growth rates are associated with higher P uptake efficiency.

PMID- 29332151
TI  - 1H, 13C and 15N backbone and partial side-chain resonance assignments of the C
      terminal domain of HIV-1 Pr55Gag encompassed in NCp15.
AB  - During HIV-1 assembly, the Pr55Gag polyprotein precursor (Gag) interacts with the
      genomic RNA, with lipids of the plasma membrane, with host proteins (ALIX,
      TSG101) through the ESCRT complex, with the viral protein Vpr and are involved in
      intermolecular interactions with other Pr55Gag proteins. This network of
      interactions is responsible for the formation of the viral particle, the
      selection of genomic RNA and the packaging of Vpr. The C-terminal domain of Gag
      encompassed in NCp15 is involved in the majority of these interactions, either by
      its nucleocapsid or its p6 domains. We study the NCp15 protein as a model of the
      C-terminal domain of Gag to better understand the role of this domain in the
      assembly and budding of HIV-1. Here, we report the 1H, 13C and 15N chemical shift
      assignments of NCp15 obtained by heteronuclear multidimensional NMR spectroscopy
      as well as the analysis of its secondary structure in solution. These assignments
      of NCp15 pave the way for interaction studies with its numerous partners.

PMID- 29332150
TI  - Ectoparasite Activity During Incubation Increases Microbial Growth on Avian Eggs.
AB  - While direct detrimental effects of parasites on hosts are relatively well
      documented, other more subtle but potentially important effects of parasitism are
      yet unexplored. Biological activity of ectoparasites, apart from skin injuries
      and blood-feeding, often results in blood remains, or parasite faeces that
      accumulate and modify the host environment. In this way, ectoparasite activities
      and remains may increase nutrient availability that may favour colonization and
      growth of microorganisms including potential pathogens. Here, by the experimental
      addition of hematophagous flies (Carnus hemapterus, a common ectoparasite of
      birds) to nests of spotless starlings Sturnus unicolor during incubation, we
      explore this possible side effect of parasitism which has rarely, if ever, been
      investigated. Results show that faeces and blood remains from parasitic flies on
      spotless starling eggshells at the end of incubation were more abundant in
      experimental than in control nests. Moreover, eggshell bacterial loads of
      different groups of cultivable bacteria including potential pathogens, as well as
      species richness of bacteria in terms of Operational Taxonomic Units (OTUs), were
      also higher in experimental nests. Finally, we also found evidence of a link
      between eggshell bacterial loads and increased embryo mortality, which provides
      indirect support for a bacterial-mediated negative effect of ectoparasitism on
      host offspring. Trans-shell bacterial infection might be one of the main causes
      of embryo death and, consequently, this hitherto unnoticed indirect effect of
      ectoparasitism might be widespread in nature and could affect our understanding
      of ecology and evolution of host-parasite interactions.

PMID- 29332152
TI  - Mallory-Weiss syndrome diagnosed after tracheal extubation.

PMID- 29332148
TI  - Occurrence of pharmaceuticals and personal care products, and their associated
      environmental risks in a large shallow lake in north China.
AB  - Eighteen selected pharmaceuticals and personal care products (PPCPs), consisting
      of five non-antibiotic pharmaceuticals (N-APs), four sulfonamides (SAs), four
      tetracyclines (TCs), four macrolides (MCs), and one quinolone (QN) were detected
      in water, pore water, and sediment samples from Baiyangdian Lake, China. A total
      of 31 water samples and 29 sediment samples were collected in March 2017.
      Caffeine was detected with 100% frequency in surface water, pore water, and
      sediment samples. Carbamazepine was detected with 100% frequency in surface water
      and sediment samples. Five N-APs were prominent, with mean concentrations of 4.90
      266.24 ng/l in surface water and 5.07-14.73 MUg/kg in sediment samples. Four MCs
      were prominent, with mean concentrations of 0.97-29.92 ng/l in pore water
      samples. The total concentrations of the different classes of PPCPs followed the
      order: N-APs (53.26%) > MCs (25.39) > SAs (10.06%) > TCs (7.64%) > QNs (3.64%) in
      surface water; N-APs (42.70%) > MCs (25.43%) > TCs (14.69%) > SAs (13.90%) > QNs
      (3.24%) in sediment samples, and MCs (42.12%) > N-APs (34.80%) > SAs (11.71%) >
      TCs (7.48%) > QNs (3.88%) in pore water samples. The geographical differences of
      PPCP concentrations were largely due to anthropogenic activities. Sewage
      discharged from Baoding City and human activities around Baiyangdian Lake were
      the main sources of PPCPs in the lake. An environmental risk assessment for the
      upper quartile concentration was undertaken using calculated risk quotients and
      indicated a low or medium-high risk from 18 PPCPs in Baiyangdian Lake and its
      five upstream rivers.

PMID- 29332153
TI  - Vasoactive-inotropic score as a predictor of morbidity and mortality in adults
      after cardiac surgery with cardiopulmonary bypass.
AB  - PURPOSE: The vasoactive-inotropic score (VIS) is a scale showing the amount of
      vasoactive and inotropic support. Recently, it was suggested that the VIS after
      cardiac surgery predicts morbidity and mortality in infants. The purpose of this
      study was to evaluate the VIS at the end of surgery as a predictor of morbidity
      and mortality in adult cardiac surgery. METHODS: A retrospective cohort study of
      129 adult cardiac surgery patients was performed at a university hospital. The
      primary outcome was termed "poor outcome", which was a composite of morbidity and
      mortality. The secondary outcomes were the duration of intensive care unit (ICU)
      stay and time to first extubation. Multivariate logistic regression analysis was
      performed to evaluate the association between the VIS and poor outcomes. A
      proportional hazards model was used to evaluate the duration of the ICU stay and
      time to first extubation. RESULTS: After adjusting for the EuroSCORE,
      preoperative ejection fraction, and bypass time, a high VIS at the end of surgery
      was associated with a poor outcome with an adjusted odds ratio of 4.87 (95%
      confidence interval 1.51-18.94; p = 0.007). After controlling for the EuroSCORE
      and bypass time, patients with a high VIS experienced longer ICU stay (hazard
      ratio 1.62; 95% confidence interval 1.10-2.39; p = 0.015) and needed longer
      ventilation (hazard ration 1.87; 95% confidence interval 1.28-2.74, p = 0.001).
      CONCLUSIONS: The amount of cardiovascular support at the end of cardiac surgery
      may predict morbidity and mortality in adults.

PMID- 29332154
TI  - The influence of systemically or locally administered mesenchymal stem cells on
      tissue repair in a rat oral implantation model.
AB  - BACKGROUND: Multipotent mesenchymal stem cells (MSCs) are used clinically in
      regenerative medicine. Our previous report showed systemically injected MSCs
      improved peri-implant sealing and accelerated tissue healing. However, the risks
      of systemic MSC administration, including lung embolism, must be considered;
      therefore, their local application must be assessed for clinical safety and
      efficacy. We investigated differences in treatment effect between local and
      systemic MSC application using a rat oral implantation model. METHODS: Rat bone
      marrow-derived MSCs were isolated and culture-expanded. The rat's right maxillary
      first molars were extracted and replaced with experimental titanium implants.
      After 24 h, MSCs (1 * 106/ml) were systemically or locally injected into
      recipient rats via the tail vein (systemic group) or buccal subcutaneous tissue
      (local group), respectively. Rats treated in the absence of MSCs were included as
      a control (control group). The maxillary epithelium was assessed histologically
      after 4 weeks to evaluate laminin-332 (Ln-332) distribution and horseradish
      peroxidase invasion, as indicators of peri-implant epithelium (PIE) formation and
      PIE sealing to the implant surface, respectively. The effect of MSCs on rat oral
      epithelial cell (OEC) morphology was determined by coculture. RESULTS: Systemic
      group MSCs accumulated early at the peri-implant mucosa, while local group MSCs
      were observed in various organs prior to later accumulation around the implant
      surface. PIE formation and Ln-332-positive staining at the implant interface were
      enhanced in the systemic group compared with the local and control groups.
      Furthermore, OEC adherence on implants was reduced in high-density compared with
      low-density MSC cocultures. CONCLUSIONS: Local MSC injection was more ineffective
      than systemic MSC injection at enhancing PIE sealing around titanium implants.
      Thus, although local MSC administration has a wide range of applications, further
      investigations are needed to understand the exact cellular and molecular
      mechanisms of this approach prior to clinical use.

PMID- 29332155
TI  - Prevalence of the Pfdhfr and Pfdhps mutations among asymptomatic pregnant women
      in Southeast Nigeria.
AB  - Sulfadoxine-pyrimethamine (SP) is the recommended drug for intermittent
      preventive treatment of malaria in pregnancy in most of sub-Saharan Africa.
      Resistance to SP is related to mutations in the dhfr and dhps gene of Plasmodium
      falciparum. This study determined the prevalence of Pfdhfr and Pfdhps
      polymorphisms found in asymptomatic pregnant women attending antenatal care in
      Calabar, Nigeria. From October 2013 to November 2014, asymptomatic pregnant women
      attending antenatal care clinics were enrolled after obtaining informed consent.
      Malaria diagnosis testing was done using thick and thin smears. Dried blood spot
      filter papers were collected. Parasite DNA was extracted from the filter papers
      using a chelex extraction. Extraction was followed by nested PCR and restriction
      enzyme digestion. P. falciparum infection was detected by microscopy in 7%
      (32/459) participants. Twenty-eight P. falciparum isolates were successfully
      genotyped. In the Pfdhfr gene, the triple mutation was almost fixed; S108N
      mutation was (100%), N51I (93%) and C59R mutations (93%), whereas the I164L
      mutation was absent. The prevalence of Pfdhps S436A, A437G, A581G and A613S
      mutations was 82.1% (23/28), 96.4% (27/28), 71.4% (20/28) and 71.4% (20/28)
      respectively. The K540E mutation was absent. The prevalence of the Pfdhfr triple
      mutation IRNI was 92.9% (26/28). The efficacy of SP as IPTp in Southeast Nigeria
      may be severely threatened. The continuous monitoring of SP molecular markers of
      resistance is required to assess thresholds. The evaluation of alternative
      preventive treatment strategies and drug options for preventing malaria in
      pregnancy may be necessary.

PMID- 29332156
TI  - Enterocytozoon bieneusi genotypes in Tibetan sheep and yaks.
AB  - Few studies have been conducted on the distribution of Enterocytozoon bieneusi
      genotypes in Tibetan sheep and yaks, which live outdoors in extreme climate with
      high altitude. In this study, fecal specimens from 312 Tibetan sheep and 554 yaks
      in Qinghai, China, were collected and examined for E. bieneusi by PCR-sequence
      analysis of the ribosomal internal transcribed spacer. Among them, 73 (23.4%)
      specimens from Tibetan sheep and 40 (7.2%) from yaks were positive for E.
      bieneusi. There were eight E. bieneusi genotypes in Tibetan sheep, including
      three known ones (BEB6, COS-I, and NESH5) and five novel ones (named as CHS13
      CHS17). Similarly, seven E. bieneusi genotypes were found in yaks, including five
      known ones (J, BEB4, BEB6, COS-I, and NESH5) and two novel ones (named as CHN13
      and CHN14). Most of the E. bieneusi genotypes and all frequent ones identified in
      the study belonged to group 2. One new subgroup of genotypes was identified
      within group 1. The distribution of E. bieneusi genotypes was different between
      Tibetan sheep and yaks, with BEB6 as the dominant one (42.5%) in Tibetan sheep
      and J as the dominant one (47.5%) in yaks. These data support the occurrence of
      host adaptation among E. bieneusi genotypes within group 2.

PMID- 29332157
TI  - Acanthamoeba keratitis in Porto Alegre (southern Brazil): 28 cases and risk
      factors.
AB  - The increasing use of contact lenses worldwide has led to an increase in cases of
      Acanthamoeba keratitis, which are often associated with inappropriate cleaning of
      contact lenses and lens cases. This study aimed to retrospectively review 28
      cases of Acanthamoeba keratitis in Porto Alegre (southern Brazil) and identify
      the risk factors and clinical outcomes of affected patients. Most patients had
      higher education (66.6%), all were users of contact lenses, mostly women (67.9%).
      Most patients were soft contact lens wearers (66.7%) and 85.7% used multipurpose
      cleaning solutions. Sixteen patients (64.0%) used to wear contact lenses while
      swimming and/or bathing. Pain was the most common symptom (92.6%). For treatment,
      patients used polyhexamethylene biguanide drops (92.6%), propamidine isethionate
      drops (81.5%), chlorhexidine drops (55.6%), topical corticosteroids (63.0%), and
      systemic corticosteroids (37.0%). Herpes simplex keratitis was the most common
      misdiagnosis (72.7%). The majority of patients (76.0%) underwent a corneal
      transplant to control the disease.

PMID- 29332158
TI  - Combined sublethal irradiation and agonist anti-CD40 enhance donor T cell
      accumulation and control of autochthonous murine pancreatic tumors.
AB  - Tumor-reactive T lymphocytes can promote the regression of established tumors.
      However, their efficacy is often limited by immunosuppressive mechanisms that
      block T cell accumulation or function. ACT provides the opportunity to ameliorate
      immune suppression prior to transfer of tumor-reactive T cells to improve the
      therapeutic benefit. We evaluated the combination of lymphodepleting whole body
      irradiation (WBI) and agonist anti-CD40 (alphaCD40) antibody on control of
      established autochthonous murine neuroendocrine pancreatic tumors following the
      transfer of naive tumor-specific CD8 T cells. Sublethal WBI had little impact on
      disease outcome but did promote T cell persistence in the lymphoid organs. Host
      conditioning with alphaCD40, an approach known to enhance APC function and T cell
      expansion, transiently increased donor T cell accumulation in the lymphoid organs
      and pancreas, but failed to control tumor progression. In contrast, combined WBI
      and alphaCD40 prolonged T cell proliferation and dramatically enhanced
      accumulation of donor T cells in both the lymphoid organs and pancreas. This dual
      conditioning approach also promoted high levels of inflammation in the pancreas
      and tumor, induced histological regression of established tumors, and extended
      the lifespan of treated mice. Prolonged survival was entirely dependent upon
      adoptive transfer, but only partially dependent upon IFNgamma production by donor
      T cells. Our results identify the novel combination of two clinically relevant
      host conditioning approaches that synergize to overcome immune suppression and
      drive strong tumor-specific T cell accumulation within well-established tumors.

PMID- 29332160
TI  - Determination of the Critical Micelle Concentration of Neutral and Ionic
      Surfactants with Fluorometry, Conductometry, and Surface Tension-A Method
      Comparison.
AB  - Micelles are of increasing importance as versatile carriers for hydrophobic
      substances and nanoprobes for a wide range of pharmaceutical, diagnostic,
      medical, and therapeutic applications. A key parameter indicating the formation
      and stability of micelles is the critical micelle concentration (CMC). In this
      respect, we determined the CMC of common anionic, cationic, and non-ionic
      surfactants fluorometrically using different fluorescent probes and fluorescence
      parameters for signal detection and compared the results with conductometric and
      surface tension measurements. Based upon these results, requirements, advantages,
      and pitfalls of each method are discussed. Our study underlines the versatility
      of fluorometric methods that do not impose specific requirements on surfactants
      and are especially suited for the quantification of very low CMC values.
      Conductivity and surface tension measurements yield smaller uncertainties
      particularly for high CMC values, yet are more time- and substance consuming and
      not suitable for every surfactant.

PMID- 29332162
TI  - Roles of Irisin in the Linkage from Muscle to Bone During Mechanical Unloading in
      Mice.
AB  - Mechanical unloading induces disuse muscle atrophy and bone loss, but the details
      in mechanism involved in those pathophysiological conditions are not fully
      understood. Interaction between muscle and bone has been recently noted. Here, we
      investigated the roles of humoral factors linking muscle to bone during
      mechanical unloading using mice with hindlimb unloading (HU) and sciatic
      neurectomy (SNX). HU and SNX reduced muscle volume surrounding the tibia, tissue
      weights of soleus and gastrocnemius muscle, and trabecular bone mineral density
      (BMD) in the tibia of mice. Among humoral factors linking muscle to bone, HU and
      SNX reduced fibronectin type III domain-containing 5 (FNDC5) mRNA levels in the
      soleus muscle of mice. Simple regression analysis revealed that FNDC5 mRNA levels
      in the soleus muscle were positively related to trabecular BMD in the tibia of
      control and HU mice as well as sham and SNX mice. Moreover, FNDC5 mRNA levels
      were negatively correlated with receptor activator of nuclear factor-kappaB
      ligand (RANKL) mRNA levels in the tibia of control and HU mice. Irisin, a product
      of FNDC5, suppressed osteoclast formation from mouse bone marrow cells and RANKL
      mRNA levels in primary osteoblasts. FNDC5 mRNA levels elevated by fluid shear
      stress were antagonized by bone morphogenetic protein (BMP) and
      phosphatidylinositol 3-kinase (PI3K) signaling inhibitors in myoblastic C2C12
      cells. In conclusion, the present study first showed that mechanical unloading
      reduces irisin expression in the skeletal muscle of mice presumably through BMP
      and PI3K pathways. Irisin might be involved in muscle/bone relationships
      regulated by mechanical stress in mice.

PMID- 29332161
TI  - The computed tomography adrenal wash-out analysis properly classifies cortisol
      secreting adrenocortical adenomas.
AB  - PURPOSE: Adrenocortical lesions are characterized through imaging, hormonal and
      histopathological analysis. Our aim was to compare the radiological features of
      adrenocortical lesions with their cortisol-secreting status and histopathological
      Weiss score. METHODS: Seventy five patients operated between 2004 and 2016 in the
      University Hospital of Nancy for either adrenocortical carcinomas (ACC) or
      adrenocortical adenomas (ACA) were enrolled in this study. We collected cortisol
      parameters, Computed Tomography (CT) scans (unenhanced density, wash-out (WO)
      analysis) and 18F-Fluorodeoxyglucose positron emission tomography/computed
      tomography (18F-FDG PET/CT) datas. The histopathological Weiss score ultimately
      differentiates ACA (score <= 2) from ACC (score >= 3). One-way ANOVA, Fisher's
      exact and unpaired t tests were used for statistical analysis with significancy
      reached at p < 0.05. RESULTS: There were 23 ACC and 52 ACA with 40 patients (53%)
      who had an autonomous secretion of cortisol. On CT scan, ACC were larger compared
      to ACA (108 vs. 37 mm, p < 0.0001). A roughly similar proportion of cortisol
      secreting (22/25) and non-secreting (15/19) ACA were atypical (i.e., unenhanced
      density value >= 10 Hounsfield Units [HU]), however 85% of cortisol-secreting vs.
      40% of non-secreting ACA were classified as benigns by the relative WO analysis
      (p = 0.08). Likewise, there was a trend for a higher 18F-FDG uptake in cortisol
      secreting ACA compared to non-secreting ACA (p = 0.053). CONCLUSIONS: The
      relative adrenal WO analysis consolidates the benign nature of an ACA, especially
      in case of cortisol oversecretion, a condition known to compromise the diagnostic
      accuracy of the 10 HU unenhanced CT attenuation threshold.

PMID- 29332163
TI  - The monkey is not always a God: Attitudinal differences toward crop-raiding
      macaques and why it matters for conflict mitigation.
AB  - Attitudinal differences toward wildlife have important implications for conflict
      management and when the species in question have strong cultural and religious
      associations, conflict mitigation becomes a challenging endeavor. We investigated
      farmers' attitudes toward two different crop-raiding macaque species, the rhesus
      macaque in northern India, and the bonnet macaque in southern India. Apart from
      regional differences in attitudes, we also assessed temporal changes in attitude
      toward the rhesus macaque. We carried out household surveys using a
      semistructured questionnaire to collect data. Our findings reveal that
      respondents in southern and northern India differ significantly in their views
      regarding species sanctity and preference for mitigation options. Although
      people's perceptions of the rhesus macaques had changed over time in northern
      India, farmers were still unwilling to cause harm to the macaques. We discuss the
      underlying causes of these observed differences in attitude and their impact on
      the management of human-macaque conflict.

PMID- 29332159
TI  - Transposable elements: genome innovation, chromosome diversity, and centromere
      conflict.
AB  - Although it was nearly 70 years ago when transposable elements (TEs) were first
      discovered "jumping" from one genomic location to another, TEs are now recognized
      as contributors to genomic innovations as well as genome instability across a
      wide variety of species. In this review, we illustrate the ways in which active
      TEs, specifically retroelements, can create novel chromosome rearrangements and
      impact gene expression, leading to disease in some cases and species-specific
      diversity in others. We explore the ways in which eukaryotic genomes have evolved
      defense mechanisms to temper TE activity and the ways in which TEs continue to
      influence genome structure despite being rendered transpositionally inactive.
      Finally, we focus on the role of TEs in the establishment, maintenance, and
      stabilization of critical, yet rapidly evolving, chromosome features: eukaryotic
      centromeres. Across centromeres, specific types of TEs participate in genomic
      conflict, a balancing act wherein they are actively inserting into centromeric
      domains yet are harnessed for the recruitment of centromeric histones and
      potentially new centromere formation.

PMID- 29332164
TI  - Skewing of the genetic architecture at the ZMYM3 human-specific 5' UTR short
      tandem repeat in schizophrenia.
AB  - Differential expansion of a number of human short tandem repeats (STRs) at the
      critical core promoter and 5' untranslated region (UTR) support the hypothesis
      that at least some of these STRs may provide a selective advantage in human
      evolution. Following a genome-wide screen of all human protein-coding gene 5'
      UTRs based on the Ensembl database ( http://www.ensembl.org ), we previously
      reported that the longest STR in this interval is a (GA)32, which belongs to the
      X-linked zinc finger MYM-type containing 3 (ZMYM3) gene. In the present study, we
      analyzed the evolutionary implication of this region across evolution and
      examined the allele and genotype distribution of the "exceptionally long" STR by
      direct sequencing of 486 Iranian unrelated male subjects consisting of 196 cases
      of schizophrenia (SCZ) and 290 controls. We found that the ZMYM3 transcript
      containing the STR is human-specific (ENST00000373998.5). A significant allele
      variance difference was observed between the cases and controls (Levene's test
      for equality of variances F = 4.00, p < 0.03). In addition, six alleles were
      observed in the SCZ patients that were not detected in the control group
      ("disease-only" alleles) (mid p exact < 0.0003). Those alleles were at the
      extreme short and long ends of the allele distribution curve and composed 4% of
      the genotypes in the SCZ group. In conclusion, we found skewing of the genetic
      architecture at the ZMYM3 STR in SCZ. Further, we found a bell-shaped
      distribution of alleles and selection against alleles at the extreme ends of this
      STR. The ZMYM3 STR sets a prototype, the evolutionary course of which determines
      the range of alleles in a particular species. Extreme "disease-only" alleles and
      genotypes may change our perspective of adaptive evolution and complex disorders.
      The ZMYM3 gene "exceptionally long" STR should be sequenced in SCZ and other
      human-specific phenotypes/characteristics.

PMID- 29332165
TI  - Factors Associated with Anxiety About Colonoscopy: The Preparation, the
      Procedure, and the Anticipated Findings.
AB  - BACKGROUND: Previous research has assessed anxiety around colonoscopy procedures,
      but has not considered anxiety related to different aspects related to the
      colonoscopy process. AIMS: Before colonoscopy, we assessed anxiety about: bowel
      preparation, the procedure, and the anticipated results. We evaluated
      associations between patient characteristics and anxiety in each area. METHODS:
      An anonymous survey was distributed to patients immediately prior to their
      outpatient colonoscopy in six hospitals and two ambulatory care centers in
      Winnipeg, Canada. Anxiety was assessed using a visual analog scale. For each
      aspect, logistic regression models were used to explore associations between
      patient characteristics and high anxiety. RESULTS: A total of 1316 respondents
      completed the questions about anxiety (52% female, median age 56 years). Anxiety
      scores > 70 (high anxiety) were reported by 18% about bowel preparation, 29%
      about the procedure, and 28% about the procedure results. High anxiety about
      bowel preparation was associated with female sex, perceived unclear instructions,
      unfinished laxative, and no previous colonoscopies. High anxiety about the
      procedure was associated with female sex, no previous colonoscopies, and
      confusing instructions. High anxiety about the results was associated with
      symptoms as an indication for colonoscopy and instructions perceived as
      confusing. CONCLUSIONS: Fewer people had high anxiety about preparation than
      about the procedure and findings of the procedure. There are unique predictors of
      anxiety about each colonoscopy aspect. Understanding the nuanced differences in
      aspects of anxiety may help to design strategies to reduce anxiety, leading to
      improved acceptance of the procedure, compliance with preparation instructions,
      and less discomfort with the procedure.

PMID- 29332166
TI  - Imaging in juvenile idiopathic arthritis - international initiatives and ongoing
      work.
AB  - Imaging is increasingly being integrated into clinical practice to improve
      diagnosis, disease control and outcome in children with juvenile idiopathic
      arthritis. Over the last decades several international groups have been launched
      to standardize and validate different imaging techniques. To enhance transparency
      and facilitate collaboration, we present an overview of ongoing initiatives.

PMID- 29332168
TI  - Efficient CRISPR/Cas9-based genome editing in carrot cells.
AB  - KEY MESSAGE: The first report presenting successful and efficient carrot genome
      editing using CRISPR/Cas9 system. Clustered Regularly Interspaced Short
      Palindromic Repeats (CRISPR)/CRISPR-associated (Cas9) is a powerful genome
      editing tool that has been widely adopted in model organisms recently, but has
      not been used in carrot-a model species for in vitro culture studies and an
      important health-promoting crop grown worldwide. In this study, for the first
      time, we report application of the CRISPR/Cas9 system for efficient targeted
      mutagenesis of the carrot genome. Multiplexing CRISPR/Cas9 vectors expressing two
      single-guide RNA (gRNAs) targeting the carrot flavanone-3-hydroxylase (F3H) gene
      were tested for blockage of the anthocyanin biosynthesis in a model purple
      colored callus using Agrobacterium-mediated genetic transformation. This approach
      allowed fast and visual comparison of three codon-optimized Cas9 genes and
      revealed that the most efficient one in generating F3H mutants was the
      Arabidopsis codon-optimized AteCas9 gene with up to 90% efficiency. Knockout of
      F3H gene resulted in the discoloration of calli, validating the functional role
      of this gene in the anthocyanin biosynthesis in carrot as well as providing a
      visual marker for screening successfully edited events. Most resulting mutations
      were small Indels, but long chromosome fragment deletions of 116-119 nt were also
      generated with simultaneous cleavage mediated by two gRNAs. The results
      demonstrate successful site-directed mutagenesis in carrot with CRISPR/Cas9 and
      the usefulness of a model callus culture to validate genome editing systems.
      Given that the carrot genome has been sequenced recently, our timely study sheds
      light on the promising application of genome editing tools for boosting basic and
      translational research in this important vegetable crop.

PMID- 29332169
TI  - Measuring cochlear duct length in Asian population: worth giving a thought!
AB  - INTRODUCTION: The anatomy of the cochlea forms the basis for a successful
      cochlear implantation. Cochlear duct length (CDL) is defined as the length of the
      scala media as measured from the middle of the round window to helicotrema.
      Preoperative measurement of CDL is particularly important when precise
      intracochlear electrode array placement is desired. It can be done both
      histologically and radiologically. Preoperative high-resolution computed
      tomography (HRCT) scan which forms an integral part of cochlear implant workup is
      a useful tool to calculate CDL using 3D reconstructions. METHOD: This study was
      done in SMS Medical College and Hospital, Jaipur, India, which is a tertiary care
      hospital and referral centre for cochlear implants. HRCT temporal bones of all
      children less than 6 years of age, with congenital bilateral severe-to-profound
      SNHL who were being worked up for cochlear implant were studied and analysed. 124
      patients (56 females and 68 males) with hearing loss were evaluated for cochlear
      implantation. HRCT temporal bone of these patients was analysed and a variable A
      was measured which is defined as the linear measurement from the round window to
      the farthest point on the opposite wall of the cochlea on a reformatted CT scan
      slice. RESULTS: Mean of distance A for right ear of these patients was 8.10 mm
      (range 7.7-9.2 mm). Mean for the same in left ear of these patients was 8.14 mm
      (range 7.7-9.0 mm), giving an overall average of 8.12 mm. Using the formula, CDL
      = 4.16A-3.98, we calculated the length of cochlear duct. Mean cochlear duct
      length was 29.8 mm with a range from 28 to 34.3 mm. CONCLUSION: To the best of
      our knowledge, this is the first large sample study of cochlear length in
      population of this part of the world. A smaller cochlear length in this part of
      the world as compared to the Caucasian cochlear duct is a significant finding in
      understanding of the cochlear anatomy and physiology. It would also have great
      implications on the insertion depth in cochlear implantation.

PMID- 29332170
TI  - MiRNA-mRNA crosstalk in laryngeal squamous cell carcinoma based on the TCGA
      database.
AB  - BACKGROUND: The functional characterization of non-coding microRNAs (miRNAs) has
      been shown to be associated with the pathophysiology of the disease, but it is
      still a challenging task to elucidate the pathogenesis of microRNAs and disease.
      In addition, the understanding of the role of miRNAs in the development of LSCC
      still needs further exploration. MATERIALS AND METHODS: In this study, to
      identify miRNAs that play a key role in LSCC, we analyzed miRNA and mRNA sequence
      data from 162 LSCC samples from the TCGA database, and screened specific miRNAs
      and mRNAs by differential gene expression analysis. And then, construct a
      differentially expressed miRNAs and mRNAs interaction network. RESULTS: In our
      investigation, 23 miRNAs (P < 0.01, log2FoldChange > 2) and 331 mRNAs (P < 0.01,
      log2FoldChange > 4) were identified differentially expressed in LSCC and reduced
      the number of loosely linked miRNAs and mRNAs according to appropriate
      thresholds. Finally, 13 miRNAs and 35 mRNAs were enriched in a network.
      CONCLUSIONS: Our study provides the most comprehensive information on the
      expression of miRNAs in LSCC and identifies the known oncogenic miRNAs (such as
      miR-163a), as well as aberrant expression of novel miRNAs involved in cell
      regulation and metabolic defects that occur during development of LSCC.

PMID- 29332167
TI  - Non-coding RNAs and plant male sterility: current knowledge and future prospects.
AB  - KEY MESSAGE: Latest outcomes assign functional role to non-coding (nc) RNA
      molecules in regulatory networks that confer male sterility to plants. Male
      sterility in plants offers great opportunity for improving crop performance
      through application of hybrid technology. In this respect, cytoplasmic male
      sterility (CMS) and sterility induced by photoperiod (PGMS)/temperature (TGMS)
      have greatly facilitated development of high-yielding hybrids in crops.
      Participation of non-coding (nc) RNA molecules in plant reproductive development
      is increasingly becoming evident. Recent breakthroughs in rice definitively
      associate ncRNAs with PGMS and TGMS. In case of CMS, the exact mechanism through
      which the mitochondrial ORFs exert influence on the development of male
      gametophyte remains obscure in several crops. High-throughput sequencing has
      enabled genome-wide discovery and validation of these regulatory molecules and
      their target genes, describing their potential roles performed in relation to
      CMS. Discovery of ncRNA localized in plant mtDNA with its possible implication in
      CMS induction is intriguing in this respect. Still, conclusive evidences linking
      ncRNA with CMS phenotypes are currently unavailable, demanding complementing
      genetic approaches like transgenics to substantiate the preliminary findings.
      Here, we review the recent literature on the contribution of ncRNAs in conferring
      male sterility to plants, with an emphasis on microRNAs. Also, we present a
      perspective on improved understanding about ncRNA-mediated regulatory pathways
      that control male sterility in plants. A refined understanding of plant male
      sterility would strengthen crop hybrid industry to deliver hybrids with improved
      performance.

PMID- 29332171
TI  - Long-term patient-related outcome measures of septoplasty: a systematic review.
AB  - PURPOSE: Septoplasty is a common rhinological procedure intended to relieve
      symptoms of chronic nasal obstruction. However, there remains a question as to
      whether patients obtain symptom improvement and are satisfied with surgical
      outcomes in the months and years after septoplasty. This review aims to evaluate
      the long-term efficacy of functional septoplasty for nasal septal deviation.
      METHODS: A systematic review of the literature was conducted from November 2014
      to March 2016 using the Cochrane, EMBASE, and PubMed databases. Prospective
      trials concerning functional septoplasty, which assessed subjective outcomes and
      included long-term follow-up data (>= 9 month post-septoplasty) were included.
      RESULTS: 2189 articles were screened with seven meeting the criteria for
      inclusion. Patient satisfaction was assessed in six studies, with rates of
      satisfaction provided in three of these, ranging from 69 to 100%. Two studies
      assessed the degree of patient satisfaction, with one study indicating that 88%
      of patients were moderately satisfied or better at 1 year post-op, and the other
      reporting that 50% of patients were satisfied. In assessing symptom relief,
      several methods were used, including validated questionnaires, with varying
      degrees of improvement in nasal obstruction reported. CONCLUSIONS: Septoplasty
      appears to be a far from perfect treatment for nasal obstruction due to septal
      deviation. However, given the heterogeneity of data and lack of randomized
      controlled trials (RCTs), future RCTs and use of validated questionnaires would
      enable generation of superior levels of evidence. We suggest future prospective
      trials evaluating prognostic factors in septoplasty, to better inform patients
      and facilitate the development of guidelines for surgical intervention.

PMID- 29332172
TI  - Spirituality as a protective health asset for young people: an international
      comparative analysis from three countries.
AB  - OBJECTIVES: Spirituality has been proposed as a potential health asset a
      'developmental engine' that works by fostering the search for connectedness,
      meaning and purpose. The aim is to examine to what extent spiritual health might
      be protective of young people's overall health and well-being. METHODS: In 2014,
      young people aged 11, 13, and 15 years in England, Scotland and Canada were
      surveyed as part of the HBSC study (n = 26,701). The perceived importance of
      spiritual health and domains (connections with self, others, nature, and the
      transcendent) was measured in these countries. Multi-level log-binomial models
      were used to explore relationships between spiritual health and three self
      reported positive health outcomes: general health status, subjective life
      satisfaction and health complaints. RESULTS: Higher levels of perceptions of the
      importance of spiritual health, both overall and within the four domains, were
      associated with higher likelihoods of reporting each of the positive health
      outcomes. CONCLUSIONS: Spiritual health appears to operate as a protective health
      asset during adolescence and is significantly shaped by external relationships
      and connections.

PMID- 29332174
TI  - A friend in knee: CCN3 may inhibit osteoarthritis progression.
AB  - Osteoarthritis (OA) is a major clinical problem among the ageing population, yet
      no disease-modifying treatments currently exist. This issue arises, in part, due
      to the complex processes occurring in the microenvironment of articular cartilage
      that lead to osteoarthritic changes. Gaining a better understanding of these
      processes is crucial in developing a viable therapy for OA. A recent report in
      Journal of Bone Mineral Metabolism by Janune et al. (J Bone Miner Metab 35:582
      597, 2016) suggests a novel role for CCN3 in maintaining the differentiated
      phenotype of articular cartilage. This report suggests that CCN3, a member of the
      CCN family of matricellular proteins, is important for proteoglycan accumulation,
      as well as expression of type II collagen, tenascin C, and lubricin in vitro.
      Furthermore, exogenous CCN3 increased tidemark integrity and lubricin protein
      expression in a rat model of OA. These results implicate the regulation of CCN3
      as a potential therapeutic target in patients with OA.

PMID- 29332173
TI  - Is the use of emergency departments socially patterned?
AB  - OBJECTIVES: To analyse the association between patients' socioeconomic position
      (SEP) and the use of emergency departments (EDs). METHODS: This population-based
      study included all visits to ED in 2012 by inhabitants of the French Midi
      Pyrenees region, recorded by the Regional Emergency Departments Observatory. We
      compared ED visit rates and the proportion of non-severe visits according to the
      patients' SEP as assessed by the European Deprivation Index. RESULTS: We analysed
      496,388 visits. The annual ED visit rate increased with deprivation level: 165.9
      [95% CI (164.8-166.9)] visits per 1000 inhabitants among the most advantaged
      group, compared to 321.9 [95% CI (320.3-323.5)] per 1000 among the most
      disadvantaged. However, the proportion of non-severe visits was about 14% of the
      visits, and this proportion did not differ according to SEP. CONCLUSIONS:
      Although the study shows a difference of ED visit rates, the probability of a
      visit being non-severe is not meaningfully different according to SEP. This
      supports the assumption that ED visit rate variations according to SEP are mainly
      explained by SEP-related differences in health states rather than SEP-related
      differences in health behaviours.

PMID- 29332175
TI  - Breast cancer survivor's perspectives on the role different providers play in
      follow-up care.
AB  - IMPORTANCE: Significant variation in the number and types of oncologists that
      provide breast cancer follow-up exists. However, there is limited understanding
      regarding breast cancer survivors' preferences for who provides their follow-up.
      Our objective was to explore breast cancer survivors' perspectives on the goals
      of breast cancer follow-up, the preferred role for primary care providers, and
      the perceived roles of different types of oncologists during follow-up. METHODS:
      A convenience sample of stage 0-III breast cancer survivors was identified and in
      depth one-on-one interviews conducted. Data were analyzed using inductive content
      analysis. RESULTS: Survivors cited a strong preference for oncology-based follow
      up within the first 5 years after diagnosis, driven by their need for reassurance
      that cancer had not recurred. Survivors also thought that their primary care
      provider needed to be involved. Survivors assumed that oncology follow-up was
      directed by a standard protocol that included streamlining the follow-up team.
      Survivors recognized that patients with more complex cancers or challenging
      treatment courses may require more intensive follow-up and deviate from the
      standard protocol. Most survivors were comfortable deferring decisions regarding
      who participated in follow-up to the oncology team. CONCLUSIONS: Most patients
      think a streamlined approach to oncology-based breast cancer follow-up already
      occurs, driven by a standard protocol. The use of a standard protocol to provide
      guidance for which types of oncology providers should participate in breast
      cancer follow-up will streamline care and represents a significant opportunity to
      reduce unnecessary variation. This approach is especially critical given
      patients' strong preferences for oncology-based follow-up.

PMID- 29332177
TI  - Novel SERAC1 mutations in a Chinese patient presenting with parkinsonism and
      dystonia.

PMID- 29332176
TI  - Characteristics of petroleum-contaminated groundwater during natural attenuation:
      a case study in northeast China.
AB  - The objective of this study was to investigate a petroleum-contaminated
      groundwater site in northeast China. We determined the physicochemical properties
      of groundwater that contained total petroleum hydrocarbons (TPH) with a view to
      developing a scientifically robust strategy for controlling and remediating
      pollution of groundwater already contaminated with petroleum. Samples were
      collected at regular intervals and were analyzed for dissolved oxygen (DO), iron
      (Fe3+), sulfate (SO42-), electrical conductivity (Eh), pH, hydrogen carbonate
      (HCO3-), and enzyme activities of catalase (CAT), peroxidase (HRP), catechol 1,2
      dioxygenase (C12O), and catechol 2,3-dioxygenase (C23O). We used factor analysis
      in SPSS to determine the main environmental characteristics of the groundwater
      samples. The results confirmed that the study site was slightly contaminated and
      that TPH levels were decreasing slightly. Some of the physicochemical variables
      showed regular fluctuations; DO, Fe3+, and SO42- contents decreased gradually,
      while the concentrations of one of the microbial degradation products, HCO3-,
      increased. Microorganism enzyme activities decreased gradually. The
      microbiological community deteriorated noticeably during the natural attenuation
      process, so microbiological degradation of pollutants receded gradually. The HCO3
      content increased and the pH and Eh decreased gradually. The groundwater
      environment tended to be reducing.

PMID- 29332178
TI  - Association of Autism with Maternal Infections, Perinatal and Other Risk Factors:
      A Case-Control Study.
AB  - This case-control study explores the association between pregnancy/birth
      complications and other factors with Autism Spectrum Disorder (ASD) in Lebanese
      subjects aged 2-18 years. Researchers interviewed 136 ASD cases from the American
      University of Beirut Medical Center Special Kids Clinic, and 178 controls
      selected by systematic digit dialing in the Greater-Beirut area. Male gender
      (Adjusted Odds Ratio [95% CI]: 3.9 [2.2-7.0]); postpartum feeding difficulties
      (2.5 [1.2-5.4]); maternal infections/complications during pregnancy (2.9 [1.5
      5.5], 2.1 [1.1-3.9]); consanguinity (2.5 [1.0-6.0]); family history of
      psychiatric disorders (2.2 [1.1-4.4]) were risk factors for ASD. Being born
      first/second (0.52 [0.28-0.95]) and maternal psychological support during
      pregnancy (0.49 [0.27-0.89]) were negatively associated with ASD. Identifying ASD
      correlates is crucial for instigating timely screening and subsequent early
      intervention.

PMID- 29332179
TI  - Profiles and Correlates of Parent-Child Agreement on Social Anxiety Symptoms in
      Youth with Autism Spectrum Disorder.
AB  - This study characterized patterns and correlates of parent-youth agreement on
      social anxiety in youth with and without autism spectrum disorder (ASD).
      Participants (279 verbally-fluent youth aged 8-16 years, NASD = 144, NTD = 135)
      completed the SASC-R. Youth with ASD exhibited higher social anxiety across
      informants. While TD youth endorsed higher anxiety than did parents, self- and
      parent-reports did not differ in youth with ASD. For children with ASD, higher
      parent-youth agreement was associated with lower lifetime ASD symptoms and higher
      adaptive skills. For TD youth, agreement on high anxiety was associated with
      lowest adaptive skills. Demographic factors (age, verbal IQ, gender) did not
      relate to agreement for either group. In ASD, parent-child agreement on youth
      anxiety, either high or low, was associated with better outcomes.

PMID- 29332182
TI  - Correction to: Pretreatment quality of life in patients with rectal cancer is
      associated with intrusive thoughts and sense of coherence.
AB  - The original version of this article, unfortunately, contained errors.

PMID- 29332181
TI  - Management of Rotator Cuff Injuries in the Elite Athlete.
AB  - PURPOSE OF REVIEW: Rotator cuff injuries are a common cause of pain and
      dysfunction for the elite athlete and can result in time loss from participation.
      This review highlights the current management of these injuries. RECENT FINDINGS:
      Conservative management of rotator cuff injuries continues to be the "gold
      standard" in the elite athlete. This includes a comprehensive rehabilitation
      program, anti-inflammatories, and corticosteroid injections. Newer treatment
      techniques such as intramuscular dry needling and the use of biologics such as
      platelet-rich plasma and stem cells demonstrate early promising results; however,
      these modalities require further investigation to determine their effectiveness.
      Rotator cuff injuries can range from contusions and tendinopathy to full
      thickness tears. A comprehensive evaluation is needed to determine the extent of
      injury and appropriate plan of care. Management strategies can range from
      rehabilitation to operative intervention and are guided by the size of the tear,
      time of season, sport, performance limitations, and presence of concomitant
      pathology.

PMID- 29332180
TI  - CD39-adenosinergic axis in renal pathophysiology and therapeutics.
AB  - Extracellular ATP interacts with purinergic type 2 (P2) receptors and elicits
      many crucial biological functions. Extracellular ATP is sequentially hydrolyzed
      to ADP and AMP by the actions of defined nucleotidases, such as CD39, and AMP is
      converted to adenosine, largely by CD73, an ecto-5'-nucleotidase. Extracellular
      adenosine interacts with P1 receptors and often opposes the effects of P2
      receptor activation. The balance between extracellular ATP and adenosine in the
      blood and extracellular fluid is regulated chiefly by the activities of CD39 and
      CD73, which constitute the CD39-adenosinergic axis. In recent years, several
      studies have shown this axis to play critical roles in transport of water/sodium,
      tubuloglomerular feedback, renin secretion, ischemia reperfusion injury, renal
      fibrosis, hypertension, diabetic nephropathy, transplantation, inflammation, and
      macrophage transformation. Important developments include global and targeted
      gene knockout and/or transgenic mouse models of CD39 or CD73, biological or small
      molecule inhibitors, and soluble engineered ectonucleotidases to directly impact
      the CD39-adenosinergic axis. This review presents a comprehensive picture of the
      multiple roles of CD39-adenosinergic axis in renal physiology, pathophysiology,
      and therapeutics. Scientific advances and greater understanding of the role of
      this axis in the kidney, in both health and illness, will direct development of
      innovative therapies for renal diseases.

PMID- 29332183
TI  - Identification of N-arylsulfonylpyrimidones as anticancer agents.
AB  - For confirming the role of five membered ring of imidazolidinone moiety of N
      arylsulfonylimidazolidinones (7) previously reported with highly potent
      anticancer agent, a series of N-arylsulfonylpyrimidones (10a-g) and N
      arylsulfonyltetrahydropyrimidones (11a-e) were prepared and their anti
      proliferating activity was measured against human cancer cell lines (renal ACHN,
      colon HCT-15, breast MDA-MB-231, lung NCI-H23, stomach NUGC-3, and prostate PC-3)
      using XTT assay. Among them, 1-(1-acetylindolin-5-ylsulfonyl)-4
      phenyltetrahydropyrimidin-2(1H)-one (11d, mean GI50 = 3.50 uM) and ethyl 5-(2-oxo
      4-phenyltetrahydropyrimidin-1(2H)-ylsulfonyl)-indoline-1-carboxylate (11e, mean
      GI50 = 0.26 uM) showed best growth inhibitory activity against human cancer cell
      lines. Considering the activity results, N-arylsulfonyltetrahydropyrimidones (11)
      exhibited more potent activity compared to N-arylsulfonylpyrimidones (10) and
      comparable activity to N-arylsulfonylimidazolidinones (7). Especially,
      tetrahydropyrimidin-2(1H)-one analogs containing acylindolin-5-ylsulfonyl moiety
      at position 1 demonstrated their strong growth inhibitory activity against human
      cancer cell lines.

PMID- 29332184
TI  - Neurologic complications of immune checkpoint inhibitors.
AB  - Immune checkpoint inhibitors (ICPIs) have recently emerged as a novel treatment
      for cancer. These agents, transforming the field of oncology, are not devoid of
      toxicity and cause immune-related side effects which can involve any organ
      including the nervous system. In this study, we present 9 patients (7 men and 2
      women) with neurologic complications secondary to ICPI treatment. These included
      meningoencephalitis, limbic encephalitis, polyradiculitis, cranial
      polyneuropathy, myasthenic syndrome and myositis. Four patients received dual
      ICPI therapy comprised of programmed cell death-1 and cytotoxic lymphocyte
      associated protein-4 blocking antibodies. Median time to onset of neurologic
      adverse event during immune checkpoint inhibitor treatment was 8 weeks (range 5
      days-19 weeks). In all patients ICPIs were stopped and corticosteroids were
      initiated, resulting in a marked improvement in seven out of nine patients. Two
      patients, one with myositis and one with myasthenic syndrome, died. In two
      patients ICPI therapy was resumed after resolution of the neurological adverse
      event with no additional neurologic complications. This series highlights the
      very broad spectrum of neurological complications of ICPIs, emphasizes the need
      for expedited diagnosis and suggests that withholding treatment early,
      accompanied with steroid therapy, carries the potential of complete resolution of
      the neurological immune-mediated condition. Thus, a high level of suspicion and
      rapid initiation of corticosteroids are mandatory to prevent uncontrolled
      clinical deterioration, which might be fatal.

PMID- 29332185
TI  - Handedness and the risk of glioma.
AB  - Gliomas are the most common type of malignant primary brain tumor and few risk
      factors have been linked to their development. Handedness has been associated
      with several pathologic neurological conditions such as schizophrenia, autism,
      and epilepsy, but few studies have evaluated a connection between handedness and
      risk of glioma. In this study, we examined the relationship between handedness
      and glioma risk in a large case-control study (1849 glioma cases and 1354 healthy
      controls) and a prospective cohort study (326,475 subjects with 375 incident
      gliomas). In the case-control study, we found a significant inverse association
      between left handedness and glioma risk, with left-handed persons exhibiting a
      35% reduction in the risk of developing glioma [odds ratio (OR) = 0.65, 95%
      confidence interval (CI) 0.51-0.83] after adjustment for age, gender, race,
      education, and state of residence; similar inverse associations were observed for
      GBM (OR = 0.69, 95% CI 0.52-0.91), and non-GBM (OR = 0.59, 95% CI 0.42-0.82)
      subgroups. The association was consistent in both males and females, and across
      age strata, and was observed in both glioblastoma and in lower grade tumors. In
      the prospective cohort study, we found no association between handedness and
      glioma risk (hazards ratio = 0.92, 95% CI 0.67-1.28) adjusting for age, gender,
      and race. Further studies on this association may help to elucidate mechanisms of
      pathogenesis in glioma.

PMID- 29332186
TI  - Assessment of oral cancer pain, anxiety, and quality of life of oral squamous
      cell carcinoma patients with invasive treatment procedure.
AB  - PURPOSE: Depending on its stage on diagnosis, oral squamous cell carcinoma (OSCC)
      might cause excruciating pain and decreased quality of life. As for treatment,
      the treatment of OSCC might vary from chemotherapy to surgery. The objective of
      the current study was to assess the preoperative and postoperative oral cancer
      pain, anxiety, and quality of life of OSCC patients with invasive treatment
      procedure. METHODS: The current study was conducted by interviewing 21 (10 males;
      11 females) patients who had been diagnosed with stage 3 and stage 4 OSCC and
      about to go through surgery at the inpatient ward of Surgical Oncology
      Department, Hasan Sadikin Hospital, Bandung, Indonesia. A preoperative and
      interview was conducted by using the Hospital Anxiety and Depression Scale
      (HADS), the European Organization for Research and Treatment of Cancer Quality of
      Life Questionnaire (EORTC QOL)-C30, the shortened EORTC QOL Questionnaire for
      Oesophageal Cancer (OES)18, the visual analog scale (VAS), and the University of
      California San Francisco (UCSF) Oral Cancer Pain Questionnaire. All data were
      analyzed to evaluate the preoperative and postoperative effect. RESULTS: The
      current study showed a significant decrease of the postoperative oral pain (p <
      0.01) and anxiety level (p < 0.01), while postoperative patient' quality of life
      was significantly (p < 0.01) increased. CONCLUSION: Despite of the invasive
      procedure that might cause postoperative effect, OSCC patients in the current
      study showed a better quality of life after cancer removal.

PMID- 29332188
TI  - Acknowledgements to Referees.

PMID- 29332187
TI  - Human bite injuries to the head and neck: current trends and management protocols
      in England and Wales.
AB  - INTRODUCTION: Human bite injuries can be challenging in their presentation to the
      examining physician. In a study by Merchant et al., 18% of patients presenting
      with a human bite injury had suffered wounds to the head and neck region. Current
      trends in their initial management at presentation to emergency departments
      throughout England and Wales will be discussed in this paper. MATERIALS AND
      METHOD: A postal survey was sent out to 100 A&E lead clinicians. This was
      followed up by telephone enquiries to improve the response rate. The collated
      results of the survey were entered onto a spreadsheet (Microsoft Excel(c)) for
      the purpose of statistical review. RESULTS: A 68% response rate from A&E
      departments throughout England and Wales demonstrated a lack of consensus in the
      initial management and subsequent treatment of human bite injuries. Written
      protocols are in place for human bite injuries in 54.4% of units. In 100% of
      units, initial management involves irrigation +/- debridement of the wound,
      though there is a lack of agreement on the surgical management of the wound.
      77.9% of units follow 'needle stick protocols' when stratifying risk for blood
      borne viruses. CONCLUSION: Human bites pose a number of unique problems, ranging
      from cellulitis to the transmission of communicable diseases. The maxillofacial
      surgeon has the added dilemmas surrounding subsequent repair and reconstruction.
      Appreciation of the complexity of human bite injuries will ensure optimal care
      for the patient. We propose a set of guidelines developed 'in-house' to assist in
      the management of human bite injuries.

PMID- 29332189
TI  - The Arabidopsis histone chaperone FACT is required for stress-induced expression
      of anthocyanin biosynthetic genes.
AB  - KEY MESSAGE: The histone chaperone FACT is involved in the expression of genes
      encoding anthocyanin biosynthetic enzymes also upon induction by moderate high
      light and therefore contributes to the stress-induced plant pigmentation. The
      histone chaperone FACT consists of the SSRP1 and SPT16 proteins and associates
      with transcribing RNAPII (RNAPII) along the transcribed region of genes. FACT can
      promote transcriptional elongation by destabilising nucleosomes in the path of
      RNA polymerase II, thereby facilitating efficient transcription of chromatin
      templates. Transcript profiling of Arabidopsis plants depleted in SSRP1 or SPT16
      demonstrates that only a small subset of genes is differentially expressed
      relative to wild type. The majority of these genes is either up- or down
      regulated in both the ssrp1 and spt16 plants. Among the down-regulated genes,
      those encoding enzymes of the biosynthetic pathway of the plant secondary
      metabolites termed anthocyanins (but not regulators of the pathway) are
      overrepresented. Upon exposure to moderate high-light stress several of these
      genes are up-regulated to a lesser extent in ssrp1/spt16 compared to wild type
      plants, and accordingly the mutant plants accumulate lower amounts of anthocyanin
      pigments. Moreover, the expression of SSRP1 and SPT16 is induced under these
      conditions. Therefore, our findings indicate that FACT is a novel factor required
      for the accumulation of anthocyanins in response to light-induction.

PMID- 29332190
TI  - Transcriptomic profiling of developing fiber in levant cotton (Gossypium
      herbaceum L.).
AB  - Cotton (Gossypium spp.) is an imperative economic crop of the globe due to its
      natural textile fiber. Molecular mechanisms of fiber development have been
      greatly revealed in allotetraploid cotton but remained unexplored in Gossypium
      herbaceum. G. herbaceum can withstand the rigors of nature like drought and pests
      but produce coarse lint. This undesirable characteristic strongly needs the
      knowledge of fiber development at molecular basis. The present study reported the
      transcriptome sequence of the developing fiber of G. herbaceum on pyrosequencing
      and its analysis. About 1.38 million raw and 1.12 million quality trimmed reads
      were obtained followed by de novo assembly-generated 20,125 unigenes containing
      14,882 coding sequences (CDs). BLASTx-based test of homology indicated that A1
      derived transcripts shared a high similarity with Gossypium arboreum (A2).
      Functional annotation of the CDs using the UniProt categorized them into
      biological processes, cellular components, and molecular function, COG
      classification showed that a large number of CDs have significant homology in COG
      database (6215 CDs), and mapping of CDs with Kyoto Encyclopedia of Genes and
      Genomes (KEGG) database generated 200 pathways ultimately showing predominant
      engagement in the fiber development process. Transcription factors were predicted
      by comparison with Plant Transcription Factor Database, and their differential
      expression between stages exposed their important regulatory role in fiber
      development. Differential expression analysis based on reads per kilobase of
      transcript per million mapped reads (RPKM) value revealed activities of specific
      gene related to carbohydrate and lipid synthesis, carbon metabolism, energy
      metabolism, signal transduction, etc., at four stages of fiber development, and
      was validated by qPCR. Overall, this study will help as a valuable foundation for
      diploid cotton fiber improvement.

PMID- 29332192
TI  - How Participatory Should Environmental Governance Be? Testing the Applicability
      of the Vroom-Yetton-Jago Model in Public Environmental Decision-Making.
AB  - Public participation is potentially useful to improve public environmental
      decision-making and management processes. In corporate management, the Vroom
      Yetton-Jago normative decision-making model has served as a tool to help managers
      choose appropriate degrees of subordinate participation for effective decision
      making given varying decision-making contexts. But does the model recommend
      participatory mechanisms that would actually benefit environmental management?
      This study empirically tests the improved Vroom-Jago version of the model in the
      public environmental decision-making context. To this end, the key variables of
      the Vroom-Jago model are operationalized and adapted to a public environmental
      governance context. The model is tested using data from a meta-analysis of 241
      published cases of public environmental decision-making, yielding three main sets
      of findings: (1) The Vroom-Jago model proves limited in its applicability to
      public environmental governance due to limited variance in its recommendations.
      We show that adjustments to key model equations make it more likely to produce
      meaningful recommendations. (2) We find that in most of the studied cases, public
      environmental managers (implicitly) employ levels of participation close to those
      that would have been recommended by the model. (3) An ANOVA revealed that such
      cases, which conform to model recommendations, generally perform better on
      stakeholder acceptance and environmental standards of outputs than those that
      diverge from the model. Public environmental management thus benefits from
      carefully selected and context-sensitive modes of participation.

PMID- 29332191
TI  - Genome-wide characterization of differentially expressed genes provides insights
      into regulatory network of heat stress response in radish (Raphanus sativus L.).
AB  - Heat stress (HS) causes detrimental effects on plant morphology, physiology, and
      biochemistry that lead to drastic reduction in plant biomass production and
      economic yield worldwide. To date, little is known about HS-responsive genes
      involved in thermotolerance mechanism in radish. In this study, a total of 6600
      differentially expressed genes (DEGs) from the control and Heat24 cDNA libraries
      of radish were isolated by high-throughput sequencing. With Gene Ontology (GO)
      and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, some genes
      including MAPK, DREB, ERF, AP2, GST, Hsf, and Hsp were predominantly assigned in
      signal transductions, metabolic pathways, and biosynthesis and abiotic stress
      responsive pathways. These pathways played significant roles in reducing stress
      induced damages and enhancing heat tolerance in radish. Expression patterns of 24
      candidate genes were validated by reverse-transcription quantitative PCR (RT
      qPCR). Based mainly on the analysis of DEGs combining with the previous miRNAs
      analysis, the schematic model of HS-responsive regulatory network was proposed.
      To counter the effects of HS, a rapid response of the plasma membrane leads to
      the opening of specific calcium channels and cytoskeletal reorganization, after
      which HS-responsive genes are activated to repair damaged proteins and ultimately
      facilitate further enhancement of thermotolerance in radish. These results could
      provide fundamental insight into the regulatory network underlying heat tolerance
      in radish and facilitate further genetic manipulation of thermotolerance in root
      vegetable crops.

PMID- 29332193
TI  - Melanogenesis inhibitory activity of components from Salam leaf (Syzygium
      polyanthum) extract.
AB  - In order to identify a novel whitening agent, the methanol extract of S.
      polyanthum leaf was focused on by the screening test using nine Indonesian
      medicinal plants for the inhibition of melanogenesis and tyrosinase activity in
      B16 melanoma cells. Three novel compounds [(1) 1-(2,3,5-trihydroxy-4
      methylphenyl)hexane-1-one, (2) 1-(2,3,5-trihydroxy methylphenyl)octane-1-one, and
      (3) (4E)-1-(2,3,5-trihydroxy-4-methylphenyl)decan-1-one and one known compound
      [(4) 1-(2,3,5-trihydroxy-4-methylphenyl)decan-1-one were isolated from the
      methanol extract. Our study demonstrated that S. polyanthum leaf methanol extract
      at 25-200 MUg/mL decreased extracellular melanin formation ca. 20-80%, with high
      cell viability. Compounds 1-4 were found to be active in melanogenesis and
      tyrosinase inhibition. Compound 3 was the most active against tyrosinase activity
      (83.98 MUM), particularly when L-tyrosine was the substrate. Compounds 1-4
      significantly diminished extracellular melanin formation in B16 melanoma cells (>
      80%), with high cell viability. Thus, our study suggested that compounds 1-4
      isolated from the methanol extract of S. polyanthum leaf play important roles in
      decreasing extracellular melanogenesis and inhibiting tyrosinase.

PMID- 29332194
TI  - The active glycosides from Urtica fissa rhizome decoction.
AB  - Using bioassay guided fractionation, 16 glycosides, including two new compounds
      (1 and 2), were isolated from the anticomplement and anti-inflammatory portion of
      an Urtica fissa rhizome decoction used for arthritis. Several compounds were
      found to possess significant anticomplement and anti-inflammatory activities.
      This study revealed that glycosides played an important role in the therapeutic
      effects of Urtica fissa rhizome.

PMID- 29332195
TI  - Histomorphometry and cortical robusticity of the adult human femur.
AB  - Recent quantitative analyses of human bone microanatomy, as well as theoretical
      models that propose bone microstructure and gross anatomical associations, have
      started to reveal insights into biological links that may facilitate remodeling
      processes. However, relationships between bone size and the underlying cortical
      bone histology remain largely unexplored. The goal of this study is to determine
      the extent to which static indicators of bone remodeling and vascularity,
      measured using histomorphometric techniques, relate to femoral midshaft cortical
      width and robusticity. Using previously published and new quantitative data from
      450 adult human male (n = 233) and female (n = 217) femora, we determine if these
      aspects of femoral size relate to bone microanatomy. Scaling relationships are
      explored and interpreted within the context of tissue form and function. Analyses
      revealed that the area and diameter of Haversian canals and secondary osteons,
      and densities of secondary osteons and osteocyte lacunae from the sub-periosteal
      region of the posterior midshaft femur cortex were significantly, but not
      consistently, associated with femoral size. Cortical width and bone robusticity
      were correlated with osteocyte lacunae density and scaled with positive
      allometry. Diameter and area of osteons and Haversian canals decreased as the
      width of cortex and bone robusticity increased, revealing a negative allometric
      relationship. These results indicate that microscopic products of cortical bone
      remodeling and vascularity are linked to femur size. Allometric relationships
      between more robust human femora with thicker cortical bone and histological
      products of bone remodeling correspond with principles of bone functional
      adaptation. Future studies may benefit from exploring scaling relationships
      between bone histomorphometric data and measurements of bone macrostructure.

PMID- 29332197
TI  - Identification as a Mutation Carrier and Effects on Life According to Experiences
      of Finnish Male BRCA1/2 Mutation Carriers.
AB  - Earlier studies have explored post-identification experiences of male BRCA1/2
      mutation carriers, but more detailed knowledge of both their experiences and
      effects of identification as a carrier on their lives is required to improve
      genetic counseling. Thus, the aim of this study was to acquire deeper and broader
      insights into their experiences. Qualitative data were collected from theme-based
      interviews with 31 men carrying BRCA1/2 mutations in Finland, and analyzed using
      inductive content analysis. Three categories of the participants' responses to
      identification as BRCA1/2 mutation carriers were identified (personal, offspring
      related and related to other relatives), mainly concerning issues associated with
      cancer, hereditary transmission of their mutations, and life decisions. Although
      there were many neutral responses regarding the issues, there were also strong
      emotional reactions and cancer worries. Identification as a carrier also had
      several effects on participants' lifestyles, including adoption of healthier and
      disease-preventing behavior, and social well-being, such as family planning and
      attitudes to life. The results provide detailed information about several aspects
      of male BRCA1/2 mutation carriers' experiences, which could be used to develop a
      tentative model of tailored genetic counseling for them.

PMID- 29332196
TI  - Bioelectronic modulation of carotid sinus nerve activity in the rat: a potential
      therapeutic approach for type 2 diabetes.
AB  - AIMS/HYPOTHESIS: A new class of treatments termed bioelectronic medicines are now
      emerging that aim to target individual nerve fibres or specific brain circuits in
      pathological conditions to repair lost function and reinstate a healthy balance.
      Carotid sinus nerve (CSN) denervation has been shown to improve glucose
      homeostasis in insulin-resistant and glucose-intolerant rats; however, these
      positive effects from surgery appear to diminish over time and are heavily
      caveated by the severe adverse effects associated with permanent loss of
      chemosensory function. Herein we characterise the ability of a novel
      bioelectronic application, classified as kilohertz frequency alternating current
      (KHFAC) modulation, to suppress neural signals within the CSN of rodents.
      METHODS: Rats were fed either a chow or high-fat/high-sucrose (HFHSu) diet (60%
      lipid-rich diet plus 35% sucrose drinking water) over 14 weeks. Neural interfaces
      were bilaterally implanted in the CSNs and attached to an external pulse
      generator. The rats were then randomised to KHFAC or sham modulation groups.
      KHFAC modulation variables were defined acutely by respiratory and cardiac
      responses to hypoxia (10% O2 + 90% N2). Insulin sensitivity was evaluated
      periodically through an ITT and glucose tolerance by an OGTT. RESULTS: KHFAC
      modulation of the CSN, applied over 9 weeks, restored insulin sensitivity
      (constant of the insulin tolerance test [KITT] HFHSu sham, 2.56 +/- 0.41%
      glucose/min; KITT HFHSu KHFAC, 5.01 +/- 0.52% glucose/min) and glucose tolerance
      (AUC HFHSu sham, 1278 +/- 20.36 mmol/l * min; AUC HFHSu KHFAC, 1054.15 +/- 62.64
      mmol/l * min) in rat models of type 2 diabetes. Upon cessation of KHFAC, insulin
      resistance and glucose intolerance returned to normal values within 5 weeks.
      CONCLUSIONS/INTERPRETATION: KHFAC modulation of the CSN improves metabolic
      control in rat models of type 2 diabetes. These positive outcomes have
      significant translational potential as a novel therapeutic modality for the
      purpose of treating metabolic diseases in humans.

PMID- 29332198
TI  - Drug Delivery and Transport into the Central Circulation: An Example of Zero
      Order In vivo Absorption of Rotigotine from a Transdermal Patch Formulation.
AB  - BACKGROUND AND OBJECTIVE: Pharmacokinetic studies using deconvolution methods and
      non-compartmental analysis to model clinical absorption of drugs are not well
      represented in the literature. The purpose of this research was (1) to define the
      system of equations for description of rotigotine (a dopamine receptor agonist
      delivered via a transdermal patch) absorption based on a pharmacokinetic model
      and (2) to describe the kinetics of rotigotine disposition after single and
      multiple dosing. METHODS: The kinetics of drug disposition was evaluated based on
      rotigotine plasma concentration data from three phase 1 trials. In two trials,
      rotigotine was administered via a single patch over 24 h in healthy subjects. In
      a third trial, rotigotine was administered once daily over 1 month in subjects
      with early-stage Parkinson's disease (PD). A pharmacokinetic model utilizing
      deconvolution methods was developed to describe the relationship between drug
      release from the patch and plasma concentrations. Plasma-concentration over time
      profiles were modeled based on a one-compartment model with a time lag, a zero
      order input (describing a constant absorption via skin into central circulation)
      and first-order elimination. Corresponding mathematical models for single- and
      multiple-dose administration were developed. RESULTS: After single-dose
      administration of rotigotine patches (using 2, 4 or 8 mg/day) in healthy
      subjects, a constant in vivo absorption was present after a minor time lag (2-3
      h). On days 27 and 30 of the multiple-dose study in patients with PD, absorption
      was constant during patch-on periods and resembled zero-order kinetics.
      CONCLUSION: Deconvolution based on rotigotine pharmacokinetic profiles after
      single- or multiple-dose administration of the once-daily patch demonstrated that
      in vivo absorption of rotigotine showed constant input through the skin into the
      central circulation (resembling zero-order kinetics). Continuous absorption
      through the skin is a basis for stable drug exposure.

PMID- 29332199
TI  - Analysis of the data on pregnancy and lactation provided by patient information
      leaflets of anti-rheumatic drugs in Argentina.
AB  - To analyse the level of consistency and updating of the information on pregnancy
      and lactation provided by patient information leaflets (PILs) of the
      antirheumatic drugs approved in Argentina. Inconsistencies between the 2016 EULAR
      Task Force recommendations on the use of anti-rheumatic drugs during pregnancy
      and lactation and the information provided by PILs of the same drugs approved in
      Argentina were analysed along with inconsistencies within the PILs of different
      registered trademarks of these drugs. Eighty-eight PILs of 32 drugs were
      analysed. Out of the 88 PILs, 50% presented information inconsistencies as to
      pregnancy. Medications comprised in this group were: hydroxychloroquine,
      sulfasalazine, azathioprine, tacrolimus, cyclosporine, NSAIDs (during the first
      two trimesters), celecoxib, some glucocorticoids, colchicine, and some anti-TNF
      drugs (etanercept, adalimumab and infliximab) during part of the pregnancy. As
      for lactation, 56% had information inconsistencies. Medications encompassed in
      this group were: hydroxychloroquine, chloroquine, sulfasalazine, azathioprine,
      tacrolimus, cyclosporine, NSAIDs, celecoxib, meprednisone, prednisone,
      colchicine, and anti-TNF drugs. Out of 17 drugs that had more than one registered
      trademark, information inconsistencies on pregnancy were found in the PILs of
      sulfasalazine, diclofenac, ibuprofen and methylprednisolone. Concerning
      lactation, inconsistencies were present in the PILs of hydroxychloroquine,
      sulfasalazine, diclofenac, ibuprofen, meprednisone, and colchicine. At least half
      of the PILs of anti-rheumatic drugs analysed in this study had information
      inconsistencies on pregnancy and lactation. This is a serious state of affairs
      because the consensual decision-making process between patient and professional
      may be compromised, which, in turn, may give rise to medical-legal issues.

PMID- 29332200
TI  - Simultaneous multi-slice accelerated turbo spin echo of the knee in pediatric
      patients.
AB  - PURPOSE: To compare knee MRI performed with the integrated parallel acquisition
      technique (PAT) and simultaneous multislice (SMS) turbo spin echo (TSE) T2
      weighted (T2w) sequences with conventional TSE sequences in pediatric patients.
      MATERIALS AND METHODS: This was a retrospective IRB-approved study. Seventy-four
      subjects (26 male, 48 female, mean age 15.3 years, range 8-20) underwent 3-T MRI
      of the knee with a T2w TSE pulse sequence prototype with four-fold PAT and SMS
      acceleration as well as the standard PAT-only accelerated sequences. Images were
      anonymized and two study folders were created: one examination with only T2w PAT2
      images (conventional examination) and one examination with only T2w SMS2/PAT2
      sequences (SMS examination). Two readers rated examinations for 15 specific
      imaging findings and 5 quality metrics. Interreader agreement was measured.
      Signal to noise (SNR) and contrast to noise (CNR) were measured for SMS and
      conventional T2w sequences. RESULTS: Consensus review demonstrated diagnostic
      quality performance of SMS examinations with respect to all 15 structures.
      Average area under the curve (AROC) was 0.95 and 0.97 for readers 1 and 2,
      respectively. The conventional sequence was favored over SMS for four out of five
      quality metrics (p < 0.001). SNR and CNR were higher for the conventional
      sequences compared to SMS. CONCLUSION: SMS accelerated T2w TSE sequences offer a
      faster alternative for knee imaging in pediatric patients without compromise in
      diagnostic performance despite diminished SNR. The four-fold acceleration of SMS
      is beneficial to pediatric patients who often have difficulty staying still for
      long MRI examinations.

PMID- 29332201
TI  - Gouty involvement of the patella and extensor mechanism of the knee mimicking
      aggressive neoplasm. A case series.
AB  - Gout is a common inflammatory crystal deposition disease that occurs in many
      joints throughout the body. Active gout is most often associated with painful
      synovitis causing searing joint pains, but gout can also produce large masses of
      space-occupying deposits called tophi. Tophi are most frequently seen in juxta
      articular locations with or without bony erosion and are often misdiagnosed as
      degenerative joint disease. Soft tissue deposits and tendon involvement are also
      known manifestations of gout, but can present with indeterminate and alarming
      findings on imaging. We present three cases of tophaceous gout mimicking
      aggressive neoplasms in the extensor mechanism of the knee. All cases presented
      as extensor tendon masses eroding into the patella, with imaging findings
      initially concerning for primary musculoskeletal malignancy.

PMID- 29332202
TI  - Non-amidated and amidated members of the C-type allatostatin (AST-C) family are
      differentially distributed in the stomatogastric nervous system of the American
      lobster, Homarus americanus.
AB  - The crustacean stomatogastric nervous system (STNS) is a well-known model for
      investigating neuropeptidergic control of rhythmic behavior. Among the peptides
      known to modulate the STNS are the C-type allatostatins (AST-Cs). In the lobster,
      Homarus americanus, three AST-Cs are known. Two of these, pQIRYHQCYFNPISCF (AST-C
      I) and GNGDGRLYWRCYFNAVSCF (AST-C III), have non-amidated C-termini, while the
      third, SYWKQCAFNAVSCFamide (AST-C II), is C-terminally amidated. Here, antibodies
      were generated against one of the non-amidated peptides (AST-C I) and against the
      amidated isoform (AST-C II). Specificity tests show that the AST-C I antibody
      cross-reacts with both AST-C I and AST-C III, but not AST-C II; the AST-C II
      antibody does not cross-react with either non-amidated peptide. Wholemount
      immunohistochemistry shows that both subclasses (non-amidated and amidated) of
      AST-C are distributed throughout the lobster STNS. Specifically, the antibody
      that cross-reacts with the two non-amidated peptides labels neuropil in the CoGs
      and the stomatogastric ganglion (STG), axons in the superior esophageal (son) and
      stomatogastric (stn) nerves, and ~ 14 somata in each commissural ganglion (CoG).
      The AST-C II-specific antibody labels neuropil in the CoGs, STG and at the
      junction of the sons and stn, axons in the sons and stn, ~ 42 somata in each CoG,
      and two somata in the STG. Double immunolabeling shows that, except for one soma
      in each CoG, the non-amidated and amidated peptides are present in distinct sets
      of neuronal profiles. The differential distributions of the two AST-C subclasses
      suggest that the two peptide groups are likely to serve different modulatory
      roles in the lobster STNS.

PMID- 29332203
TI  - Custom-made, antibiotic-loaded, acrylic cement spacers using a dental silicone
      template for treatment of infected hip prostheses.
AB  - PURPOSE: Antibiotic-loaded acrylic cement (ALAC) spacers are useful for treatment
      of infected prostheses in the course of a two-stage revision. Spacers are
      handmade or are made using a commercial template, with reportedly good treatment
      outcomes. This study aimed to confirm the usefulness of custom-made ALAC spacers
      shaped like bipolar hip prostheses using a dental silicone template for treatment
      of infected hip prostheses, and described their manufacture. METHODS: This study
      evaluated 10 patients who underwent two-stage revision for treatment of infected
      hip prostheses. Custom-made ALAC spacers were used in all patients. Templates
      were made with dental silicone. We investigated the following in treatment of the
      infected hip prostheses: bacterial pathogens; antibiotic-cement mixtures; waiting
      time to revision; dislocation, breakage, and migration of custom-made ALAC
      spacers; current hip status; progress during follow-up; presence or absence of
      recurrence; and walking ability. RESULTS: Dislocation, breakage, and migration
      were not observed in custom-made ALAC spacers. All patients recovered after two
      stage revision without additional surgery and showed no recurrence during the
      follow-up period. CONCLUSION: Custom-made ALAC spacers shaped like bipolar hip
      prostheses using a template made of dental silicone may be useful for treatment
      of infected hip prostheses.

PMID- 29332204
TI  - Supplementing living kidney transplantees' medical records with donor- and
      recipient-narratives.
AB  - Norway provides total social welfare coverage for organ transplantations,
      including free immunosuppressive medication and prepaid life-long follow up for
      both recipients and donors. Despite these benefits the proportion of living
      kidney donors (LKD) has in recent years declined from around 40% (2011) of all
      kidney transplantations to 24% (2016). This study suggests harnessing patient-
      and donor-narratives as a tool for addressing the current fall in donation rates.
      The hospital records of 18 recipient/donor dyads were compared with patient and
      donor accounts elicited in semi-structured interviews. Narratives afford a
      pertinent supplement to the primarily biomedical and technical information stored
      in medical records. Even in condensed form, the messages embedded in narratives
      contribute to a 'thicker' understanding of the complexity of living kidney
      donation (LKD)-decisions. Narratives represent a source of education for
      referring-nephrologists wishing to deepen their evaluation skills and avoid
      making decisions based on insufficient insight into patients' and potential
      donors' values and life-situation. Recipients' and donors' unedited accounts of
      their motivations, worries, doubts and expectations afford a revealing and
      edifying supplement to the primarily biomedical and technical information stored
      in medical records. In narratives, the predicaments and dilemmas surrounding LKD
      become visible and debatable and can serve as support for future donors,
      recipients and the nephrologists responsible for evaluation-conclusions.
      Generating narratives raises a number of practical, epistemic and normative
      challenges.

PMID- 29332205
TI  - Microbiome in psychiatry: where will we go?

PMID- 29332206
TI  - Oncological outcomes after cytoreductive nephrectomy for patients with metastatic
      renal cell carcinoma with inferior vena caval tumor thrombus.
AB  - BACKGROUND: To evaluate the oncological outcomes of patients with metastatic
      renal cell carcinoma (mRCC) involving the inferior vena cava (IVC) who received
      cytoreductive nephrectomy. METHODS: This study included 75 consecutive metastatis
      renal cell carcinoma (mRCC) patients with inferior vena cava (IVC) tumor thrombus
      undergoing cytoreductive nephrectomy and tumor thrombectomy followed by systemic
      therapy. RESULTS: Of the 75 patients, 11, 33, 24 and 7 had level I, II, III and
      IV IVC thrombus, respectively. Following surgical treatment, 25 (group A), 27
      (group B) and 23 (group C) received cytokine therapy alone, molecular-targeted
      therapy alone and both therapies, respectively, as management for metastatic
      diseases. The median overall survival (OS) of the 75 patients was 16.2 months. No
      significant differences in OS were noted according to the level of the IVC tumor
      thrombus. There were no significant differences in OS among groups A, B and C;
      however, OS in groups B and C was significantly superior to that in group A.
      Furthermore, multivariate analysis of several parameters identified the following
      independent predictors of poor OS-elevated C-reactive protein, liver metastasis
      and postoperative treatment with cytokine therapy alone. CONCLUSIONS: The
      prognosis of mRCC patients with IVC thrombus undergoing cytoreductive nephrectomy
      may be significantly affected by the type of postoperative systemic therapy
      rather than the level of the IVC tumor thrombus. Accordingly, cytoreductive
      nephrectomy should be considered as a major therapeutic option for patients with
      mRCC involving the IVC, particularly in the era of targeted therapy.

PMID- 29332207
TI  - Skeletal muscle expression of p43, a truncated thyroid hormone receptor alpha,
      affects lipid composition and metabolism.
AB  - Thyroid hormone is a major regulator of metabolism and mitochondrial function.
      Thyroid hormone also affects reactions in almost all pathways of lipids
      metabolism and as such is considered as the main hormonal regulator of lipid
      biogenesis. The aim of this study was to explore the possible involvement of p43,
      a 43 Kda truncated form of the nuclear thyroid hormone receptor TRalpha1 which
      stimulates mitochondrial activity. Therefore, using mouse models overexpressing
      p43 in skeletal muscle (p43-Tg) or lacking p43 (p43-/-), we have investigated the
      lipid composition in quadriceps muscle and in mitochondria. Here, we reported in
      the quadriceps muscle of p43-/- mice, a fall in triglycerides, an inhibition of
      monounsaturated fatty acids (MUFA) synthesis, an increase in elongase index and
      an decrease in desaturase index. However, in mitochondria from p43-/- mice, fatty
      acid profile was barely modified. In the quadriceps muscle of p43-Tg mice, MUFA
      content was decreased whereas the unsaturation index was increased. In addition,
      in quadriceps mitochondria of p43-Tg mice, we found an increase of linoleic acid
      level and unsaturation index. Last, we showed that cardiolipin content, a key
      phospholipid for mitochondrial function, remained unchanged both in quadriceps
      muscle and in its mitochondria whatever the mice genotype. In conclusion, this
      study shows that muscle lipid content and fatty acid profile are strongly
      affected in skeletal muscle by p43 levels. We also demonstrate that regulation of
      cardiolipin biosynthesis by the thyroid hormone does not imply p43.

PMID- 29332208
TI  - Localised aggressive periodontitis in a 3-year-old-boy.
AB  - BACKGROUND: Localised aggressive periodontitis (LAgP), characterised by rapid
      attachment and bone loss, which may occur in children and adolescents, without
      clinical evidence of systemic disease. CASE REPORT: Three-year-old boy was
      referred with excessive mobility of 83 and exfoliation of 73. Clinical
      examination revealed acceptable oral hygiene. Blood tests were performed to
      evaluate PMNs activity and the parents were advised to apply 0.2% chlorhexidine
      twice a day. One month later 83 was still excessively mobile. Blood tests were
      normal. TREATMENT: A full mouth scaling and curettage were performed under
      general anaesthesia. Since 83 had been spontaneously exfoliated one day earlier,
      a biopsy was taken from its socket. The biopsy examination revealed granulation
      tissue with actinomyces colonies. A course of amoxicillin 250 mg three times a
      day for 7 days was prescribed. Cultures from periodontal pockets of the child's
      family members were found negative to Aggregatibacter actinomycetem comitans
      (Aa). FOLLOW-UP: Examination 3 months later, no tooth mobility was observed and
      the cultures from the periodontal pockets were negative to Aa. Thereafter, the
      child was periodically reviewed every 3 months for 26 months with no signs of
      periodontal disease. CONCLUSION: Amoxicillin combined with curettage around the
      involved teeth may be effective in LAgP treatment.

PMID- 29332209
TI  - The rapid diagnosis of viral respiratory tract infections and its impact on
      antimicrobial stewardship programs.
AB  - We aimed to describe the potential benefit of new rapid molecular respiratory
      tests (MRT) in decreasing inappropriate antibiotic use among the inpatients
      presenting with influenza-like illness (ILI). We included patients from inpatient
      and outpatient departments who had ILI and performed MRT between 1 January 2015
      and 31 December 2016 in a 265-bed private hospital in Istanbul. At the end of
      2015, we implemented antimicrobial stewardship including systematic use of MRT.
      Then, we compared our observations between the year 2015 and the year 2016. We
      designed the study according to the STrengthening the Reporting of OBservational
      studies in Epidemiology (STROBE) tool. A U.S. Food and Drug Administration (FDA)
      cleared multiplexed polymerase chain reaction (PCR) system (BioFire FilmArray,
      Idaho Technology, Salt Lake City, UT) which detects 17 viruses and three bacteria
      was used for diagnosis. In total, 1317 patients were included; 630 (48%) were
      inpatients and 569 (43%) were older than 16 years of age. At least one virus was
      detected in 747 (57%) patients. Rhinovirus/enterovirus, influenza virus, and
      adenovirus were the most commonly detected. Among hospitalized patients, in
      children, a significant decrease in antibiotic use (44.5% in 2015 and 28.8% in
      2016, p = 0.009) was observed, but in adults, the decrease was not statistically
      significant (72% in 2015 and 63% in 2016, p = 0.36). The duration of antibiotic
      use after the detection of virus was significantly decreased in both children and
      adults (p < 0.001 and p = 0.007, respectively). By using MRT, inappropriate
      antibiotic use and, also, duration of inappropriate antibiotic use after the
      detection of virus was significantly decreased. It is time to increase the
      awareness about the viral etiology in respiratory tract infections (RTIs) and
      implement MRT in clinical practice.

PMID- 29332210
TI  - Pathogen-specific leptospiral proteins in urine of patients with febrile illness
      aids in differential diagnosis of leptospirosis from dengue.
AB  - Leptospirosis and dengue are two commonly seen infectious diseases of the
      tropics. Differential diagnosis of leptospirosis from dengue fever is often
      difficult due to overlapping clinical symptoms and lack of economically viable
      and easy-to-perform laboratory tests. The gold standard for diagnosis is the
      microscopic agglutination test (MAT). In this study, the diagnostic potential of
      screening for pathogen-specific leptospiral antigens in urine samples is
      presented as a non-invasive method of disease diagnosis. In a study group of 40
      patients, the serum was tested for anti-leptospiral antibodies by MAT and enzyme
      linked immunosorbent assay (ELISA). Urine of these patients was screened for
      leptospiral antigens by ELISA using specific antibodies against LipL32, LipL41,
      Fla1, HbpA and sphingomyelinase. Group I patients (n = 23) were classified as
      leptospirosis-positive based on MAT and high titres of circulating IgM-specific
      anti-leptospiral antibodies. All of these patients excreted all five leptospiral
      antigens in the urine. The 17 MAT-negative cases included six patients with
      pyrexia of unknown origin (PUO; Group II) and 11 confirmed dengue patients (Group
      III). The latter tested negative for both serum anti-leptospiral antibodies and
      urinary leptospiral antigens. A salient outcome of this study was highlighting
      the usefulness of screening for urinary leptospiral antigens in disease
      diagnosis, as their presence confirmed leptospiral aetiology in two PUO patients.
      Immunoblots of urinary antigens identified well-defined bands corresponding to
      LipL32, HbpA and sphingomyelinase; the significance of the 42- and 58-kDa
      sphingomyelinase bands is discussed.

PMID- 29332211
TI  - Testosterone-mediated upregulation of delayed rectifier potassium channel in
      cardiomyocytes causes abbreviation of QT intervals in rats.
AB  - Men have shorter rate-corrected QT intervals (QTc) than women, especially at the
      period of adolescence or later. The aim of this study was to elucidate the long
      term effects of testosterone on cardiac excitability parameters including
      electrocardiogram (ECG) and potassium channel current. Testosterone shortened QT
      intervals in ECG in castrated male rats, not immediately after, but on day 2 or
      later. Expression of Kv7.1 (KCNQ1) mRNA was significantly upregulated by
      testosterone in cardiomyocytes of male and female rats. Short-term application of
      testosterone was without effect on delayed rectifier potassium channel current
      (IKs), whereas IKs was significantly increased in cardiomyocytes treated with
      dihydrotestosterone for 24 h, which was mimicked by isoproterenol (24 h). Gene
      selective inhibitors of a transcription factor SP1, mithramycin, abolished the
      effects of testosterone on Kv7.1. Testosterone increases Kv7.1-IKs possibly
      through a pathway related to a transcription factor SP1, suggesting a genomic
      effect of testosterone as an active factor for cardiac excitability.

PMID- 29332213
TI  - Survivorship care plan outcomes for primary care physicians, cancer survivors,
      and systems: a scoping review.
AB  - PURPOSE: With the focus on survivorship care-coordination between oncology and
      primary care providers (PCPs), there is a need to assess the research regarding
      the use of survivorship care plans (SCPs) and determine emerging research areas.
      We sought to find out how primary care physicians have been involved in the use
      of SCPs and determine SCP's effectiveness in improving care for cancer survivors.
      In this scoping review, we aimed to identify gaps in the current research and
      reveal opportunities for further research. METHODS: We followed the methodology
      for scoping studies which consists of identifying the research question, locating
      relevant studies, selecting studies, charting the data, and collating,
      summarizing, and reporting the results. RESULTS: Out of 5375 original articles
      identified in the literature search, 25 met the inclusion/exclusion criteria.
      Eight articles examined PCP-only related outcomes, eight examined survivor-only
      related outcomes, eight examined mixed outcomes between both groups, and one
      examined system-based outcomes. Findings highlighted several areas where SCPs may
      provide benefits, including increased confidence among PCPs in managing the care
      of survivors and increased quality of life and well-being for survivors. This
      research also highlighted the need for careful consideration of SCP mode of
      delivery and content in order to maximize their utility to patients and
      providers. CONCLUSIONS: Based on the findings of this review, SCPs may benefit
      providers and health care systems, but the benefits to patients remain unclear.
      Further research on the potential benefits of SCPs to particular patient
      populations is warranted. IMPLICATIONS FOR CANCER SURVIVORS: SCPs appear to be
      beneficial to PCPs in improving overall quality of care. However, more work needs
      to be done to understand the direct impact on cancer survivors.

PMID- 29332212
TI  - Measurement of [Cl-]i unaffected by the cell volume change using MQAE-based two
      photon microscopy in airway ciliary cells of mice.
AB  - MQAE is a 'non-ratiometric' chloride ion (Cl-)-quenched fluorescent indicator
      that is used to determine intracellular Cl- concentration ([Cl-]i). MQAE-based
      two-photon microscopy is reported to be a useful method to measure [Cl-]i, but it
      is still controversial because a change in cell volume may alter the MQAE
      concentration, leading to a change in the fluorescence intensity without any
      change in [Cl-]i. In an attempt to elucidate the effect or lack of effect of cell
      volume on MQAE concentration, we studied the effects of changes in cell volume,
      achieved by applying different levels of osmotic stress, on the intensity of MQAE
      fluorescence in airway ciliary cells. To study solely the effect of changes in
      cell volume on MQAE fluorescence intensity, i.e., excluding the effect of any
      change in [Cl-]i, we first conducted the experiments in a Cl--free nitrate (NO3-)
      solution to substitute NO3- (non-quenching anion for MQAE fluorescence) for Cl-
      in the intracellular fluid. Hypo- (- 30 mM NaNO3) or hyper-osmotic stress (+ 30
      mM NaNO3) effected changes in cell volume, but the stress did not result in any
      significant change in MQAE fluorescence intensity. The experiments were also
      carried out in Cl--containing solution. Hypo-osmotic stress (- 30 mM NaCl)
      increased both MQAE fluorescence intensity and cell volume, while hyper-osmotic
      stress (+ 30 mM NaCl) decreased both of these properties. These results suggest
      that the osmotic stress-induced change in MQAE fluorescence intensity was caused
      by the change in [Cl-]i and not by the MQAE concentration. Moreover, the
      intracellular distribution of MQAEs was heterogeneous and not affected by the
      changes in osmotic stress-induced cell volume, suggesting that MQAEs are bound to
      un-identified subcellular structures. These bound MQAEs appear to have enabled
      the measurement of [Cl-]i in airway ciliary cells, even under conditions of cell
      volume change.

PMID- 29332214
TI  - Targeted Next-Generation Sequencing in Patients with Non-syndromic Congenital
      Heart Disease.
AB  - Congenital heart disease (CHD) is a genetically heterogeneous disease. Targeted
      next-generation sequencing (NGS) offers a unique opportunity to sequence multiple
      genes at lower cost and effort compared to Sanger sequencing. We tested a
      targeted NGS of a specific gene panel in a relatively large population of non
      syndromic CHD patients. The patient cohort comprised 68 CHD patients (45 males;
      8.3 +/- 1.7 years). Amplicon libraries for 16 CHD-strictly related genes were
      generated using a TruSeq(r) Custom Amplicon kit (Illumina, CA) and sequenced
      using the Illumina MiSeq platform. Sequence data were processed through the MiSeq
      Reporter and wANNOVAR softwares. After applying stringent filtering criteria, 20
      missense variants in 9 genes were predicted to be damaging and were validated by
      Sanger sequencing with 100% concordance. Fourteen variants were present in public
      databases with very rare allele frequency, of which four variants (p.Arg25Cys in
      NKX2-5, p.Val763Ile in ZFPM2, p.Arg1398Gln and Gly1826Asp in MYH6) have been
      previously linked to CHD or cardiomyopathy. The remaining six variants in four
      genes (GATA4, NKX2-5, NOTCH1, TBX1) were novel mutations, currently not found in
      public databases, and absent in 200 control alleles of healthy subjects. Four
      patients (5.8%) carried two missense variants (1 compound heterozygote in the
      same gene and 3 double heterozygotes in different genes), with possibly
      synergistic deleterious effects. Targeted NGS is a powerful and efficient tool to
      detect DNA sequence variants in multiple genes, providing the opportunity for
      discovery of the co-occurrence of two or more missense rare variants.

PMID- 29332215
TI  - Heparin-Coated Grafts Reduce Mortality in Pediatric Patients Receiving Systemic
      to-Pulmonary Shunts.
AB  - We aimed to evaluate the outcomes of systemic-to-pulmonary (SP) shunt procedures
      utilizing heparin-coated (HC) polytetrafluoroethylene (PTFE) vascular grafts
      compared to uncoated (non-HC) grafts, in order to observe any benefits in
      pediatric patients. Our institution switched from using non-HC grafts to HC
      grafts in March 2011. We conducted a retrospective review of consecutive
      pediatric patients receiving SP shunts from May 2008 to December 2015.
      Perioperative variables including baseline characteristics, morbidity, mortality,
      and blood product utilization were evaluated between the HC and non-HC groups. A
      total of 142 pediatric patients received SP shunts during the study period: 69
      patients received HC shunts and 73 patients received non-HC shunts. The HC group
      had significantly fewer desaturation or arrest events (P < 0.01), fewer shunt
      occlusions/thromboses (P < 0.01). There was no statistically significant
      difference in unplanned reoperations between groups (P = 0.18). The HC group
      demonstrated significantly lower overall 30-day mortality (P < 0.01), as well as
      shunt-related mortality (P < 0.01). The HC group had significantly lower
      postoperative packed red blood cell utilization as compared to the non-HC group
      (P < 0.01). In this study, pediatric patients receiving HC PTFE grafts in SP
      shunts demonstrated significantly lower shunt-related mortality. The majority of
      HC grafts remained patent. These findings suggest that HC grafts used in SP shunt
      procedures may benefit pediatric patients in terms of efficacy and outcomes.

PMID- 29332216
TI  - Characteristics of ARG-carrying plasmidome in the cultivable microbial community
      from wastewater treatment system under high oxytetracycline concentration.
AB  - Studies on antibiotic production wastewater have shown that even a single
      antibiotic can select for multidrug resistant bacteria in aquatic environments.
      It is speculated that plasmids are an important mechanism of multidrug resistance
      (MDR) under high concentrations of antibiotics. Herein, two metagenomic libraries
      were constructed with plasmid DNA extracted from cultivable microbial communities
      in a biological wastewater treatment reactor supplemented with 0 (CONTROL) or 25
      mg/L of oxytetracycline (OTC-25). The OTC-25 plasmidome reads were assigned to 72
      antibiotic resistance genes (ARGs) conferring resistance to 13 types of
      antibiotics. Dominant ARGs, encoding resistance to tetracycline, aminoglycoside,
      sulfonamide, and multidrug resistance genes, were enriched in the plasmidome
      under 25 mg/L of oxytetracycline. Furthermore, 17 contiguous multiple-ARG
      carrying contigs (carrying >= 2 ARGs) were discovered in the OTC-25 plasmidome,
      whereas only nine were found in the CONTROL. Mapping of the OTC-25 plasmidome
      reads to completely sequenced plasmids revealed that the conjugative IncU
      resistance plasmid pFBAOT6 of Aeromonas caviae, carrying multidrug resistance
      transporter (pecM), tetracycline resistance genes (tetA, tetR), and transposase
      genes, might be a potential prevalent resistant plasmid in the OTC-25 plasmidome.
      Additionally, two novel resistant plasmids (containing contig C301682 carrying
      multidrug resistant operon mexCD-oprJ and contig C301632 carrying the tet36 and
      transposases genes) might also be potential prevalent resistant plasmids in the
      OTC-25 plasmidome. This study will be helpful to better understand the role of
      plasmids in the development of MDR in water environments under high antibiotic
      concentrations.

PMID- 29332217
TI  - A novel glucuronoyl esterase from Aspergillus fumigatus-the role of conserved Lys
      residue in the preference for 4-O-methyl glucuronoyl esters.
AB  - Cellulose in plant cell walls is mainly covered by hemicellulose and lignin, and
      thus efficient removal of these components is thought to be a key step in the
      optimal utilization of lignocellulose. The recently discovered carbohydrate
      esterase (CE) 15 family of glucuronoyl esterases (GEs) which cleave the linkages
      between the free carboxyl group of D-glucuronic acid in hemicellulose and the
      benzyl groups in lignin residues could contribute to this process. Herein, we
      report the identification, functional expression, and enzymatic characterization
      of a GE, AfGE, from the filamentous fungus Aspergillus fumigatus. AfGE was
      heterologously expressed in Aspergillus oryzae, and the purified enzyme displayed
      the ability to degrade the synthetic substrates mimicking the ester linkage
      between hemicellulose and lignin. AfGE is a potentially industrially applicable
      enzyme due to its characteristic as a thermophilic enzyme with the favorable
      temperature of 40-50  degrees C at pH 5. Molecular modeling and site-directed
      mutagenesis studies of AfGE demonstrated that Lys209 plays an important role in
      the preference for the substrates containing 4-O-methyl group in the
      glucopyranose ring.

PMID- 29332218
TI  - Effects of sleep hygiene training given to pregnant women with restless leg
      syndrome on their sleep quality.
AB  - PURPOSE: This research was conducted to determine the effects of sleep hygiene
      training given to pregnant women with restless leg syndrome on their sleep
      quality. METHODS: This study was conducted using a quasi-experimental design with
      pre-test and post-test, and a control group. When the power analysis was made, a
      sample size with 5% two-sided significance, 95% confidence interval, and 95%
      ability to represent the population was calculated to have a total of 128
      pregnant women. The sleeping hygiene training was given to two sessions of the
      experiment group. A personal identification form and the Pittsburgh Sleep Quality
      Index were used for the collection of data. Percentage distribution, arithmetic
      mean, standard deviation, and chi-square were used for statistical evaluation in
      addition to dependent and independent groups t tests. RESULTS: PSQI pre-test mean
      values revealed that sleep quality in both groups was similarly poor (p = 0.353).
      It was determined that the mean post-test score after sleep hygiene training was
      7.23 +/- 2.17 in the experiment group and 10.54 +/- 2.20 in the control group,
      while the difference between the groups was statistically significant (p =
      0.000). Accordingly, it was determined that the sleepers in the experimental
      group had better sleep quality than those in the control group. CONCLUSIONS:
      Sleep hygiene training given to pregnant women with restless leg syndrome
      increased sleep quality.

PMID- 29332220
TI  - Perinatal outcomes of unplanned out-of-hospital deliveries: a case-control study.
AB  - PURPOSE: To compare the pregnancy and perinatal outcomes of unplanned home or car
      births vs. in-hospital deliveries. METHODS: A retrospective, case-control study
      of women who underwent unplanned out-of-hospital deliveries vs. in-hospital
      deliveries from 2004 through 2014. Matching was based on gestational age and
      parity in a ratio of 2:1. RESULTS: There were no significant differences between
      the groups regarding demographic criteria, prenatal care and delivery
      complications. Women who delivered out of hospital (n = 90) had significantly
      fewer cesarean deliveries (1.1 vs. 10.6%; p = 0.05) and operative deliveries (2.2
      vs. 13.3%; p = 0.004) in their obstetrical history than did the control group (n
      = 180). Significantly more newborns delivered out of the hospital had
      polycythemia (25.6 vs. 1.7%; p < 0.0001) and hypothermia (3.3 vs. 0%; p = 0.036)
      compared to the control group. CONCLUSION: Women with unplanned out-of-hospital
      deliveries tend to have fewer complications in their previous deliveries. Higher
      rates of polycythemia and hypothermia require attention for neonates born out of
      the hospital.

PMID- 29332221
TI  - German words: still used by Japanese obstetrics and gynecology doctors.
AB  - BACKGROUND: German used to be frequently employed in Japanese obstetric and
      gynecologic (OBGYN) practice; however, it is now less frequently used.
      Description and analysis of this situation may shed some light on the change of
      OBGYN practice and education in Japan, which may at least partly hold true to
      counties other than Japan. METHODS: Three eras were classified according to the
      relationship between German and Japanese OBGYN, with each era characterized.
      Frequently used German words in Japanese OBGYN practice were described as
      examples. RESULTS: German words have become less frequently used with each
      successive generation. CONCLUSIONS: Even though English may suffice in practical
      OBGYN practice, German usage will still be passed on to these new generations.

PMID- 29332219
TI  - Desensitisation strategies in high-risk children before kidney transplantation.
AB  - BACKGROUND: Transplantation is the preferred modality for renal replacement
      therapy in children. With increasing rates of re-transplantation within the
      paediatric population, there are more sensitised children on waiting lists. One
      issue with developing strategies to treat these children is the number of
      different definitions of sensitisation. and we would therefore recommend an
      immunological risk stratification approach. METHODS: We discuss methods of
      sensitisation prevention, assessment and management, including paired exchange
      programmes and desensitisation protocols. RESULTS: There are limited published
      evidence-based data for desensitisation in adults and none in children; thus, we
      present information on the available therapies currently in use. DISCUSSION:
      Further research is required to investigate strategies which prevent
      sensitisation in children, including the healthcare utility of incorporating
      epitope-based matching into organ allocation algorithms. Controlled studies are
      also needed to establish the most appropriate desensitisation regimen(s).

PMID- 29332222
TI  - Efficacy of Crocus sativus (saffron) in treatment of major depressive disorder
      associated with post-menopausal hot flashes: a double-blind, randomized, placebo
      controlled trial.
AB  - PURPOSE: Due to concerns regarding the side effects of hormone therapy, many
      studies have focused on the development of non-hormonal agents for treatment of
      hot flashes. The aim of this study was to evaluate the efficacy and safety of
      saffron (stigma of Crocus sativus) in treatment of major depressive disorder
      associated with post-menopausal hot flashes. METHODS: Sixty women with post
      menopausal hot flashes participated in this study. The patients randomly received
      either saffron (30 mg/day, 15 mg twice per day) or placebo for 6 weeks. The
      patients were assessed using the Hot Flash-Related Daily Interference Scale
      (HFRDIS), Hamilton Depression Rating Scale (HDRS) and the adverse event checklist
      at baseline and also at the second, fourth, and sixth weeks of the study.
      RESULTS: Fifty-six patients completed the trial. Baseline characteristics of the
      participants did not differ significantly between the two groups. General linear
      model repeated measures demonstrated significant effect for time * treatment
      interaction on the HFRDIS score [F (3, 162) = 10.41, p = 0.0001] and HDRS score
      [F (3, 162) = 5.48, p = 0.001]. Frequency of adverse events was not significantly
      different between the two groups. CONCLUSIONS: Results from this study revealed
      that saffron is a safe and effective treatment in improving hot flashes and
      depressive symptoms in post-menopausal healthy women. On the other hand, saffron,
      with fewer side effects, may provide a non-hormonal and alternative herbal
      medicine option in treatment of women with hot flashes.

PMID- 29332223
TI  - Long-term efficacy of partial splenic embolization for the treatment of steroid
      resistant chronic immune thrombocytopenia.
AB  - Thrombopoietin-receptor agonists have been recently introduced for a second-line
      treatment of immune thrombocytopenia (ITP). Splenectomy has tended to be avoided
      because of its complications, but the response rate of splenectomy is 60-80% and
      it has still been considered for steroid-refractory ITP. We performed partial
      splenic embolization (PSE) as an alternative to splenectomy. Between 1988 and
      2013, 91 patients with steroid-resistant ITP underwent PSE at our hospital, and
      we retrospectively analyzed the efficacy and long-term outcomes of PSE. The
      complete response rate (CR, platelets > 100 * 109/L) was 51% (n = 46), and the
      overall response rate (CR plus response (R), > 30 * 109/L) was 84% (n = 76). One
      year after PSE, 70% of patients remained CR and R. The group with peak platelet
      count after PSE >= 300 * 109/L (n = 29) exhibited a significantly higher platelet
      count than the group with platelet count < 300 * 109/L (n = 40) at any time point
      after PSE. The failure-free survival (FFS) rates at 1, 5, and 10 years were 78,
      56, and 52%, respectively. Second PSE was performed in 20 patients who relapsed
      (n = 14) or had no response to the initial PSE (n = 6), and the overall response
      was achieved in 63% patients. There were no PSE-related deaths. These results
      indicate that PSE is a safe and effective alternative therapy to splenectomy for
      patients with steroid-resistant ITP as it generates long-term, durable responses.

PMID- 29332224
TI  - Phosphatidylserine-exposing blood and endothelial cells contribute to the
      hypercoagulable state in essential thrombocythemia patients.
AB  - The mechanisms of thrombogenicity in essential thrombocythemia (ET) are complex
      and not well defined. Our objective was to explore whether phosphatidylserine
      (PS) exposure on blood cells and endothelial cells (ECs) can account for the
      increased thrombosis and distinct thrombotic risks among mutational subtypes in
      ET. Using flow cytometry and confocal microscopy, we found that the levels of PS
      exposing erythrocytes, platelets, leukocytes, and serum-cultured ECs were
      significantly higher in each ET group [JAK2, CALR, and triple-negative (TN) (all
      P < 0.001)] than those in controls. Among ET patients, those with JAK2 mutations
      showed higher levels of PS-positive erythrocytes, platelets, neutrophils, and
      serum-cultured ECs than TN patients or those with CALR mutations, which show
      similar levels. Coagulation function assays showed that higher levels of PS
      positive blood cells and serum-cultured ECs led to markedly shortened coagulation
      time and dramatically increased levels of FXa, thrombin, and fibrin production.
      This procoagulant activity could be largely blocked by addition of lactadherin
      (approx. 70% inhibition). Confocal microscopy showed that the FVa/FXa complex and
      fibrin fibrils colocalized with PS on ET serum-cultured ECs. Additionally, we
      found a relationship between D-dimer, prothrombin fragment F1 + 2, and PS
      exposure. Our study reveals a previously unrecognized link between
      hypercoagulability and exposed PS on cells, which might also be associated with
      distinct thrombotic risks among mutational subtypes in ET. Thus, blocking PS
      binding sites may represent a new therapeutic target for preventing thrombosis in
      ET.

PMID- 29332226
TI  - Monocortical fixation of the coracoid in the Latarjet procedure is significantly
      weaker than bicortical fixation.
AB  - PURPOSE: A crucial step of the Latarjet procedure is the fixation of the coracoid
      process onto the glenoid. Multiple problems associated with the fixation have
      been described, including lesions of the suprascapular nerve due to prominence of
      the screw or bicortical drilling. The purpose of the present study was to
      evaluate whether monocortical fixation, without perforating the posterior glenoid
      cortex, would provide sufficient graft stability. METHODS: Coracoid transfer was
      performed in 14 scapula models (Sawbones(r), Composite Scapula, 4th generation).
      Two groups were assigned: in one group, fixation was achieved with two screws
      that did not perforate the posterior cortex of the glenoid neck (monocortical
      fixation), in the other group, fixation was achieved with perforation of the
      posterior cortex (bicortical fixation). The ultimate failure load and mode of
      failure were evaluated biomechanically. RESULTS: Monocortical fixation was a
      significantly weaker construct than bicortical fixation (median failure load 221
      N, interquartile range 211-297 vs. median failure load 423 N, interquartile range
      273-497; p = 0.017). Failure was either due to a pullout of the screws from the
      socket or a fracture of the glenoid. There was no significant difference in the
      mode of failure between the two groups (n.s.). CONCLUSION: Monocortical fixation
      was significantly weaker than bicortical fixation. However, bicortical drilling
      and overly long screws may jeopardize the suprascapular nerve. Thus, anatomic
      knowledge about the safe zone at the posterior rim of the glenoid is crucial.
      Until further research has evaluated, if the inferior stability is clinically
      relevant, clinicians should be cautious to use a monocortical fixation technique
      for the coracoid graft.

PMID- 29332225
TI  - Over 90 % of children and adolescents return to sport after anterior cruciate
      ligament reconstruction: a systematic review and meta-analysis.
AB  - PURPOSE: To evaluate the rate at which children and adolescent athletes return to
      sporting activities after anterior cruciate ligament (ACL) reconstruction.
      METHODS: Three databases, PubMed, MEDLINE, and EMBASE, were searched from
      database inception until September 9, 2017 by two reviewers independently and in
      duplicate. The inclusion criteria were English language studies that reported
      return to sport outcomes. Book chapters, conference papers, review articles, and
      technical reports were excluded. The rate of return to sports was combined in a
      meta-analysis of proportions using a random-effects model. RESULTS: Overall, 20
      studies with a combined total of 1156 ACL reconstructions met the inclusion
      criteria, with a mean age of 14.3 years (range 6-19) and a mean follow-up time of
      6.5 years (range 1-22). All studies were level IV evidence (14 retrospective case
      series and 6 prospective case series). The pooled rate of return to any sport
      participation was 92.0% [95% confidence interval (CI), 86-96%]. The pooled rate
      of return to pre-injury level of sport was 78.6% (95% CI 71-86%) and that to
      competitive level of sport was 81.0% (95% CI 62-94%). A total of 93 of the 717
      assessed athletes (13%) sustained re-injuries with graft ruptures, and in 91 of
      652 patients (14%), contralateral ACL injuries were reported on final follow-up.
      CONCLUSION: Pooled results suggest a high rate of return to sport following ACL
      reconstruction in children and adolescent athletes; however, this is associated
      with a relatively high rate of graft rupture and a similar rate of contralateral
      ACL injury. This study provides clinicians with evidence-based data on the
      ability of children and adolescent athletes to return to sport after ACL
      reconstruction, an important consideration for athletes of this population with
      ACL injuries. LEVEL OF EVIDENCE: IV, systematic review of level IV studies.

PMID- 29332227
TI  - Accommodative esotropia: the state of the art.
AB  - PURPOSE: To review the state of the art of Accommodative Esotropia (AE) through
      careful study of what has been reported up to the point in literature. METHODS: A
      literature search was done on PubMed using key words including "Accommodative
      esotropia", "Infantile esotropia", "Strabismus" and "Accommodation". We
      systematically reviewed and critically appraised what has been written about AE
      and we tried to analyze that according to the current management of AE. RESULTS:
      Accommodative Esotropia (AE) is a form of strabismus characterized by convergent
      misalignment of the visual axes that can be associated with hyperopia and
      abnormal fusional divergence. Also abnormal accommodative
      convergence/accommodation ratio could be found. In lots of cases, AE initially
      presents as an intermittent esodeviation at age 1.5 to 4 years. The prevalence of
      AE has been estimated near 1-2% in the United States. The only treatment with an
      optical correction usually is successful in re-establishing alignment, but
      surgical correction is necessary in approximately 30% of cases.

PMID- 29332228
TI  - Comparative evaluation of the aqueous humor proteome of primary angle closure and
      primary open angle glaucomas and age-related cataract eyes.
AB  - PURPOSE: To analyze and compare the total proteome of aqueous humor (AH) from
      patients having primary angle closure glaucoma (PACG), primary open angle
      glaucoma (POAG) and age-related cataract. MATERIALS AND METHODOLOGY: Aqueous
      humor was collected from age-matched PACG, POAG and cataract patients who
      underwent surgery, and it was immediately stored at - 80  degrees C until
      analysis. From each sample, 25 ug of total protein was subjected to trypsin
      digestion and subsequently LC-MS/MS analysis was performed for the deep proteome
      analysis. The data acquired after the LC-MS/MS analysis were analyzed using
      Proteome Discoverer 1.4. The identified peptide matches were validated using
      percolator, at less than 1% false discovery rates. RESULTS: A total of 625, 594
      and 636 proteins were identified in PACG, POAG and cataract groups, respectively
      (n = 9 in each group). The inter-group comparison among all these groups showed
      that 246 proteins were identified in all the three groups. An average of 236 +/-
      42, 218 +/- 40 and 214 +/- 62 proteins from each AH sample of PACG, POAG and
      cataract, respectively, was identified. There were 53 proteins commonly found in
      all 9 PACG AH, 59 proteins in POAG AH and 42 proteins in 9 cataracts AH samples.
      In the individual analysis, there were 28 proteins found in all the samples
      analyzed representing the "constitutive AH proteome." Spectral counting analysis
      of 246 proteins identified in all three group types showed significant
      differences in protein abundance. In proteins unique to PACG AH, 7 proteins viz.
      ARHGEF12, APC2, WAS, PIK3CG, ITGB1, MSN and PFN1 out of 226 were found in
      "Regulation of Actin Cytoskeleton" pathway, whereas in POAG 5 out of 206 proteins
      viz. ADCY2, ITPR1, MAPK3, MAP3K2 and TUBB1 were found in "Gap Junction" pathway.
      CONCLUSIONS: A qualitative as well as a quantitative comparison of proteomes of
      AH from PACG, POAG and age-related cataract eyes showed significant differences,
      thus providing clues to the disease pathophysiology.

PMID- 29332229
TI  - Sociability modifies dogs' sensitivity to biological motion of different social
      relevance.
AB  - Preferential attention to living creatures is believed to be an intrinsic
      capacity of the visual system of several species, with perception of biological
      motion often studied and, in humans, it correlates with social cognitive
      performance. Although domestic dogs are exceptionally attentive to human social
      cues, it is unknown whether their sociability is associated with sensitivity to
      conspecific and heterospecific biological motion cues of different social
      relevance. We recorded video clips of point-light displays depicting a human or
      dog walking in either frontal or lateral view. In a preferential looking
      paradigm, dogs spontaneously viewed 16 paired point-light displays showing
      combinations of normal/inverted (control condition), human/dog and
      frontal/lateral views. Overall, dogs looked significantly longer at frontal human
      point-light display versus the inverted control, probably due to its clearer
      social/biological relevance. Dogs' sociability, assessed through owner-completed
      questionnaires, further revealed that low-sociability dogs preferred the lateral
      point-light display view, whereas high-sociability dogs preferred the frontal
      view. Clearly, dogs can recognize biological motion, but their preference is
      influenced by their sociability and the stimulus salience, implying biological
      motion perception may reflect aspects of dogs' social cognition.

PMID- 29332230
TI  - A cardioid oscillator with asymmetric time ratio for establishing CPG models.
AB  - Nonlinear oscillators are usually utilized by bionic scientists for establishing
      central pattern generator models for imitating rhythmic motions by bionic
      scientists. In the natural word, many rhythmic motions possess asymmetric time
      ratios, which means that the forward and the backward motions of an oscillating
      process sustain different times within one period. In order to model rhythmic
      motions with asymmetric time ratios, nonlinear oscillators with asymmetric
      forward and backward trajectories within one period should be studied. In this
      paper, based on the property of the invariant set, a method to design the closed
      curve in the phase plane of a dynamic system as its limit cycle is proposed.
      Utilizing the proposed method and considering that a cardioid curve is a kind of
      asymmetrical closed curves, a cardioid oscillator with asymmetric time ratios is
      proposed and realized. Through making the derivation of the closed curve in the
      phase plane of a dynamic system equal to zero, the closed curve is designed as
      its limit cycle. Utilizing the proposed limit cycle design method and according
      to the global invariant set theory, a cardioid oscillator applying a cardioid
      curve as its limit cycle is achieved. On these bases, the numerical simulations
      are conducted for analyzing the behaviors of the cardioid oscillator. The example
      utilizing the established cardioid oscillator to simulate rhythmic motions of the
      hip joint of a human body in the sagittal plane is presented. The results of the
      numerical simulations indicate that, whatever the initial condition is and
      without any outside input, the proposed cardioid oscillator possesses the
      following properties: (1) The proposed cardioid oscillator is able to generate a
      series of periodic and anti-interference self-exciting trajectories, (2) the
      generated trajectories possess an asymmetric time ratio, and (3) the time ratio
      can be regulated by adjusting the oscillator's parameters. Furthermore, the
      comparison between the simulated trajectories by the established cardioid
      oscillator and the measured angle trajectories of the hip angle of a human body
      show that the proposed cardioid oscillator is fit for imitating the rhythmic
      motions of the hip of a human body with asymmetric time ratios.

PMID- 29332232
TI  - Prone position in ARDS: a simple maneuver still underused.

PMID- 29332231
TI  - Stage-specific therapeutic strategies of medication-related osteonecrosis of the
      jaws: a systematic review and meta-analysis of the drug suspension protocol.
AB  - OBJECTIVE: The most debated topic about medication-related osteonecrosis of the
      jaws (MRONJ) is its therapy, as there are no definitive guidelines. The aims of
      this systematic review were (a) to outline the best therapeutic approach
      according to the stage at diagnosis and (b) to perform a meta-analysis to assess
      whether the drug-holiday protocol may be or not an effective method in the
      management of MRONJ patients. MATERIALS AND METHODS: The systematic review was
      performed following the PRISMA principles. Results were screened according to
      inclusion and exclusion criteria regarding staging before/after treatment, follow
      up, and information provided by the authors. For statistical analysis, linear
      variables are reported as means and standard deviations, medians, and inter
      quartile range (IQR); normality of data, according to the distribution of
      complete healing (primary outcome variable), was assessed with the Kolmogorov
      Smirnov test. A p value < 0.05 was considered statistically significant for all
      tests. RESULTS: Thirteen studies were selected out of 1480. None of them was case
      controlled or randomized. Conservative approach showed good results at early
      stages, but heterogeneous result at advanced stages (100% stage 0, stage I range
      81-97%, stage II range 63.6-100%, stage III 73%). Surgical approach showed
      heterogeneous results at all stages (stage I range 0-100%, stage II range 52
      100%, stage III range 50-100%). Statistical analysis showed a significantly
      higher prevalence of completely healed sites in patients who followed the drug
      holiday protocol. CONCLUSIONS: The results suggest that the current stage
      specific approach for MRONJ therapy is based on a sound clinical rationale.
      Conservative treatment appears to yield better outcomes at early stages, while
      further investigations are needed to elucidate the best protocols for the
      management of advanced stages. The drug-holiday protocol statistically promotes
      complete healing after oral surgery procedures but the application should be
      dictated by the condition of each patient. CLINICAL RELEVANCE: At present, early
      MRONJ stages should be primarily treated by means of a conservative approach
      while more advanced stages must be carefully evaluated. Individual decisions
      should be made for every single case even with respect to the drug-holiday
      protocol.

PMID- 29332233
TI  - Pilot study of serial FLT and FDG-PET/CT imaging to monitor response to
      neoadjuvant chemoradiotherapy of esophageal adenocarcinoma: correlation with
      histopathologic response.
AB  - OBJECTIVE: The aim of this prospective pilot study was to investigate the
      potential of serial FLT-PET/CT compared to FDG-PET/CT to provide an early
      indication of esophageal cancer response to concurrent neoadjuvant chemoradiation
      therapy. METHODS: Five patients with biopsy-proven esophageal adenocarcinomas
      underwent neoadjuvant chemoradiation (Tx) prior to minimally invasive
      esophagectomy. The presence of residual tumor was classified histologically using
      the Mandard et al. criteria, categorizing patients as pathologic responders and
      non-responders. Participants underwent PET/CT imaging 1 h after intravenous
      administration of FDG and of FLT on two separate days within 48 h of each other.
      Each patient underwent a total of 3 scan "pairs": (1) pre-treatment, (2) during
      treatment, and (3) post-treatment. Image-based response to therapy was measured
      in terms of changes in SUVmax (DeltaSUV) between pre- and post-therapeutic FLT-
      and FDG-PET scans. The PET imaging findings were correlated with the pathology
      results after surgery. RESULTS: All tumors were FDG and FLT avid at baseline.
      Lesion FLT uptake was lower than with FDG. Neoadjuvant chemoradiation resulted in
      a reduction of tumor uptake of both radiotracers in pathological responders (n =
      3) and non-responders (n = 2). While the difference in the reduction in mean
      tumor FLT uptake during Tx between responders (DeltaSUV = - 55%) and non
      responders (DeltaSUV = - 29%) was significant (P = 0.007), for FDG it was not,
      [responders had a mean DeltaSUV = - 39 vs. - 31% for non-responders (P = 0.74)].
      The difference in the reduction in tumor FLT uptake at the end of treatment
      between responders (DeltaSUV = - 62%) and non-responders (DeltaSUV = - 57%) was
      not significant (P = 0.54), while for FDG there was a trend toward significance
      [DeltaSUV of responders = - 74 vs. - 52% in non-responders (P = 0.06)].
      CONCLUSION: The results of this prospective pilot study suggest that early
      changes in tumor FLT uptake may be better than FDG in predicting response of
      esophageal adenocarcinomas to neoadjuvant chemoradiation. These preliminary
      results support the need to corroborate the value of FLT-PET/CT in a larger
      cohort.

PMID- 29332234
TI  - Attitudes of U.S. Psychiatry Residents and Fellows towards Mental Illness and its
      Causes: a Comparison Study with Medical Students.
AB  - Stigma towards people with mental illness remains a burden for patients and
      healthcare providers. This study at a large US university examined the attitudes
      of psychiatry residents and fellows towards mental illness and its causes, and
      whether their attitudes differed from the medical student attitudes previously
      studied utilizing the same survey method. An electronic questionnaire examining
      attitudes toward people with mental illness, causes of mental Illness, and
      treatment efficacy was used to survey the attitudes of psychiatry residents and
      fellows. Exploratory factor analysis derived from the authors' medical student
      survey was used to examine attitudinal factors. The study response rate was 54.2%
      (n = 94). Factor analysis employed three factors previously identified reflecting
      social acceptance of mental illness, belief in supernatural causes, and belief in
      biopsychosocial causes. Residents and fellows reporting more personal experiences
      with mental illness, both as a group and when compared with medical students,
      were significantly more willing to socialize with the mentally ill. Respondents
      who had more professional (work) experience other than medical school or post
      graduate training were less likely to believe in supernatural causes of mental
      illness. Female residents and fellows were more willing to socialize with the
      mentally ill, and were less likely to believe in supernatural causes for mental
      illness than their male counterparts. In our study, increased social acceptance
      of the mentally ill relates to having personal experiences, advanced training in
      psychiatry, and female gender. Both professional experiences outside of training
      and female gender reduced the belief in supernatural causes.

PMID- 29332235
TI  - Do Diary Studies Cause Behavior Change? An Examination of Reactivity in Sexual
      Risk and Substance Use in Young Men Who Have Sex with Men.
AB  - Behavioral diaries are frequently used for observing sexual and substance use
      behaviors, but participating in diary studies may cause behavior change. This
      study examined change in sexual and substance use behaviors among young men who
      have sex with men (YMSM) in a two-month diary study compared to control. An
      analytic sample of 324 YMSM was randomized to receive daily diaries, weekly
      diaries, or no diaries (control) for 2 months. Half of the diary participants
      were randomized to receive automated weekly feedback. Between-subjects analyses
      found no evidence of change in sexual or substance use behaviors from baseline to
      2-month follow-up when comparing the diary conditions to control. Within-persons
      growth mixture models of all diary data showed significant decreases in
      condomless anal sex (CAS) and illicit drug use. Weekly automated feedback had no
      effect on behavior change. Findings provide evidence of change in CAS and illicit
      drug use amongst diary participants.

PMID- 29332236
TI  - Child Desire Among Men and Women Living with HIV/AIDS in the Traditional Culture
      of Vietnam.
AB  - In various settings, heterogeneity in fertility rates among HIV-affected couples
      highlights the importance of understanding contextual factors to inform program
      planning and implementation. We interviewed 1016 patients with HIV/AIDS at seven
      clinics in Vietnam to assess their desire to have a(nother) child and willingness
      to pay (WTP) for prevention of mother to child transmission (PMTCT) services. One
      fifth of participants reported their desire for a(another) child and this was
      slightly higher among men than women. Factors associated with the desire to have
      a(nother) child of HIV/AIDS patients included (1) not yet have a child or a son,
      (2) provincial and district-level service, (3) income per capita, (4) marital
      status and (5) history of drug injection. The average WTP for PMTCT service was
      US $179 (95% CI 161-197). The study highlights the need for interventions on
      social, cultural barriers, improved accessibility and outcomes of counseling, and
      better care and treatment services for couples and child affected by HIV/AIDS.

PMID- 29332237
TI  - Acute acetaminophen ingestion improves performance and muscle activation during
      maximal intermittent knee extensor exercise.
AB  - AIM: Acetaminophen is a commonly used medicine for pain relief and emerging
      evidence suggests that it may improve endurance exercise performance. This study
      investigated some of the physiological mechanisms by which acute acetaminophen
      ingestion might blunt muscle fatigue development. METHODS: Thirteen active males
      completed 60 * 3 s maximum voluntary contractions (MVC) of the knee extensors
      with each contraction separated by a 2 s passive recovery period. This protocol
      was completed 60 min after ingesting 1 g of maltodextrin (placebo) or 1 g of
      acetaminophen on two separate visits. Peripheral nerve stimulation was
      administered every 6th contraction for assessment of neuromuscular fatigue
      development, with the critical torque (CT), which reflects the maximal
      sustainable rate of oxidative metabolism, taken as the mean torque over the last
      12 contractions. Surface electromyography was recorded continuously as a measure
      of muscle activation. RESULTS: Mean torque (61 +/- 11 vs. 58 +/- 14% pre-exercise
      MVC) and CT (44 +/- 13 vs. 40 +/- 15% pre-exercise MVC) were greater in the
      acetaminophen trial compared to placebo (both P < 0.05). Voluntary activation and
      potentiated twitch declined at a similar rate in both conditions (P > 0.05).
      However, the decline in electromyography amplitude was attenuated in the
      acetaminophen trial, with electromyography amplitude being greater compared to
      placebo from 210 s onwards (P < 0.05). CONCLUSION: These findings indicate that
      acute acetaminophen ingestion might be ergogenic by increasing CT and preserving
      muscle activation during high-intensity exercise.

PMID- 29332238
TI  - Normal variation in sagittal spinal alignment parameters in adult patients: an
      EOS study using serial imaging.
AB  - PURPOSE: To describe normal variations in sagittal spinal radiographic parameters
      over an interval period and establish physiological norms and guidelines for
      which these images should be interpreted. METHODS: Data were prospectively
      collected from a continuous series of adult patients with first-episode mild low
      back pain presenting to a single institution. The sagittal parameters of two
      serial radiographic images taken 6-months apart were obtained with the EOS(r)
      slot scanner. Measured parameters include CL, TK, TL, LL, PI, PT, SS, and end and
      apical vertebrae. Chi-squared test and Wilcoxon Signed Rank test were used to
      compare categorical and continuous variables, respectively. RESULTS: Sixty
      patients with a total of 120 whole-body sagittal X-rays were analysed. Mean age
      was 52.1 years (SD 21.2). Mean interval between the first and second X-rays was
      126.2 days (SD 47.2). Small variations (< 1 degrees ) occur for all except PT
      (1.2 degrees ), CL (1.2 degrees ), and SVA (2.9 cm). Pelvic tilt showed
      significant difference between two images (p = 0.035). Subgroup analysis based on
      the time interval between X-rays, and between the first and second X-rays, did
      not show significant differences. Consistent findings were found for end and
      apical vertebrae of the thoracic and lumbar spine between the first and second X
      rays for sagittal curve shapes. CONCLUSIONS: Radiographic sagittal parameters
      vary between serial images and reflect dynamism in spinal balancing. SVA and PT
      are predisposed to the widest variation. SVA has the largest variation between
      individuals of low pelvic tilt. Therefore, interpretation of these parameters
      should be patient specific and relies on trends rather than a one-time
      assessment.

PMID- 29332239
TI  - Which parameters are relevant in sagittal balance analysis of the cervical spine?
      A literature review.
AB  - INTRODUCTION: Cervical spine is part of the spine with the most mobility in the
      sagittal plane. It is important for surgeons to have reliable, simple and
      reproducible parameters to analyse the cervical. MATERIAL AND METHOD: This study
      is a systematic review and a critique of current parameters to help improve the
      study of cervical spinal balance. We conducted a systematic search of
      PUBMED/MEDLINE for literature published since January 2014. Only studies written
      in English and containing abstracts were considered for inclusion. The search
      performed was: "C7 slope" OR "T1 slope" OR "C2C7 offset" OR "C2C7 lordosis" OR
      "cervical SVA (sagittal vertical axis)" OR "TIA (thoracic inlet angle)" (Lee et
      al., J Spinal Disord Tech 25(2):E41-E47, 2012) OR "SCA (spino-cranial angle)".
      Exclusion criteria were purely post-operative and cadaveric analysis, studies
      performed with CT scan or MRI, studies on adolescent idiopathic scoliosis,
      traumatology studies and no standing analysis of the cervical spine. Relevance
      was confirmed by investigators if cervical parameters was a major criteria of the
      study. RESULTS: 138 articles were found by the electronic search. After complete
      evaluation 20 articles were selected. The large majority of papers used the same
      parameters C2_C7 lordosis, C2-C7 SVA, T1 slope or C7 slope and T1 slope/cervical
      lordosis mismatch. Janusz reported a new parameter using a retrospective cohort
      of patient with cervical radiculopathy: the TIA (thoracic inlet angle). Le Huec
      reported an other new parameter based on a prospective study of asymptomatic
      volunteer: the spino-cranial angle (SCA). This parameter is highly correlated
      with the C7 slope and the cervical lordosis. Other studies reported parameters
      that are more global balance analysis including the cervical spine than cervical
      spine balance itself. CONCLUSION: The most important parameters to analyse the
      cervical sagittal balance according to the literature available today for good
      clinical outcomes are the following: C7 or T1 slope, average value 20 degrees ,
      must not be higher than 40 degrees . cSVA must not be less than 40 degrees C
      (mean value 20 mm). SCA (spine cranial angle) must stay in a norm (83 degrees  +/
      9 degrees ). Future studies should focus on those three parameters to analyse
      and compare pre and post op data and to correlate the results with the quality of
      life improvement.

PMID- 29332240
TI  - Preperitoneal closed-system suction drainage after totally extraperitoneal
      hernioplasty in the prevention of early seroma formation: a prospective double
      blind randomised controlled trial.
AB  - OBJECTIVES: Seroma is a virtually unavoidable early sequela after TEP
      hernioplasty. This randomised controlled trial evaluated the outcomes of
      preperitoneal closed-system suction drainage in laparoscopic totally
      extraperitoneal (TEP) hernioplasty for inguinal hernia. METHODS: Ninety patients
      aged 18-80 years who presented to our hospital between May 2016 and February 2017
      with primary unilateral inguinal hernia were randomised into the preperitoneal
      drain and no-drain groups. The primary outcome was seroma size on postoperative
      day 6. Secondary outcomes included clinical seroma formation and seroma size on
      day 1, day 6, 1 and 7 months postoperatively, length of postoperative stay, pain
      score, and recurrence. RESULTS: There was no significant difference in age, sex,
      co-morbidities, hernia side, mean hernia size, operating time, fixation adjuncts,
      or postoperative stay. The overall incidence of clinical seroma formation was
      25.6% on postoperative day 1, 60.3% on postoperative day 6, 13.2% 1 month and 0%
      7 months postoperatively. The mean drain output was 57.9 ml. The drain group had
      significantly fewer patients with seroma on day 1 (6 vs 14, p = 0.022) and day 6
      (17 vs 30, p = 0.000), and a smaller mean seroma size on days 1 and 6 (p =
      0.000). Subgroup analysis showed that sac ligation versus reduction, peritoneal
      perforation, and fixation adjuncts had no significant effects on seroma formation
      or size. There is a trend of lower early post-operation VAS score and more
      urinary retention in drain group was observed but not reaching statistical
      significance. No differences in postoperative pain score or complications were
      observed at 1 and 7 months' post operation. CONCLUSIONS: Preperitoneal drainage
      for 23 h after laparoscopic TEP hernioplasty for inguinal hernia can effectively
      decrease seroma formation in the early postoperative period, and potentially
      improving postoperative pain. The benefit is short-term and no significant
      difference was demonstrated after 1-month post operations. This tradition
      technique applied to novel operative repair of inguinal hernia is safe and
      feasible with no significant morbidity demonstrated. Preperitoneal drainage after
      TEP can be considered as an option to improve patient satisfactions and recovery
      in selected patient group for maximal benefit, especially for those with
      prolonged operation which may associate with higher chance of seroma formation.

PMID- 29332241
TI  - Atrial fibrillation is associated with sudden cardiac death: a systematic review
      and meta-analysis.
AB  - PURPOSE: Recent studies suggest that atrial fibrillation (AF) is associated with
      increased cardiovascular risk and mortality including sudden cardiac death (SCD).
      According to the Cardiovascular Heath Study cohort, the incident rate of SCD was
      higher in the AF population (2.9 per 1000 per year) compared with non-AF controls
      (1.3 per 1000 per year). In this study, we performed a systematic review and meta
      analysis to explore the association between AF and SCD. METHODS: We
      comprehensively searched the databases of MEDLINE and EMBASE from inception to
      January 2017. Included studies were published prospective or retrospective cohort
      studies that compared the risk of developing SCD, defined by World Health
      Organization's criteria, in AF patients versus non-AF patients. Data from each
      study were combined using the random-effects, generic inverse variance method of
      DerSimonian and Laird to calculate the risk ratios and 95% confidence intervals.
      RESULTS: Twenty-seven studies from January 1991 to February 2017 involving 8401
      AF patients and 67,608 non-AF controls were included in this meta-analysis.
      Compared with controls, AF patients had a significantly higher risk of SCD in
      overall analysis (pooled risk ratio = 2.04, 95% confidence interval: 1.77-2.35, p
      < 0.01, I2 = 42.66) as well as subgroups of general population studies, previous
      myocardial infarction or coronary artery disease, heart failure, hypertrophic
      cardiomyopathy (HCM), Brugada syndrome, and patients with either a pacemaker or
      implantable cardioverter defibrillator (ICD). In subgroup analysis of
      multivariate-adjusted studies, AF also had a significantly higher risk of SCD
      (pooled risk ratio = 2.22, 95% confidence interval = 1.59-3.09, p < 0.01, I2 =
      73.95). Incident rate of SCD in AF was 2-fold higher than controls but not
      statistically significant (pooled rate ratio = 2.06, 95% confidence interval =
      0.66-7.53, p = 0.292, I2 = 88.58). CONCLUSIONS: Our meta-analysis demonstrates a
      statistically significant increased risk of SCD with AF in the general population
      and in those with previous myocardial infarction, coronary artery disease, heart
      failure, HCM, Brugada syndrome, and an implanted rhythm device.

PMID- 29332242
TI  - Selective IKK2 inhibitor IMD0354 disrupts NF-kappaB signaling to suppress corneal
      inflammation and angiogenesis.
AB  - Corneal neovascularization is a sight-threatening condition caused by
      angiogenesis in the normally avascular cornea. Neovascularization of the cornea
      is often associated with an inflammatory response, thus targeting VEGF-A alone
      yields only a limited efficacy. The NF-kappaB signaling pathway plays important
      roles in inflammation and angiogenesis. Here, we study consequences of the
      inhibition of NF-kappaB activation through selective blockade of the IKK complex
      IkappaB kinase beta (IKK2) using the compound IMD0354, focusing on the effects of
      inflammation and pathological angiogenesis in the cornea. In vitro, IMD0354
      treatment diminished HUVEC migration and tube formation without an increase in
      cell death and arrested rat aortic ring sprouting. In HUVEC, the IMD0354
      treatment caused a dose-dependent reduction in VEGF-A expression, suppressed
      TNFalpha-stimulated expression of chemokines CCL2 and CXCL5, and diminished actin
      filament fibers and cell filopodia formation. In developing zebrafish embryos,
      IMD0354 treatment reduced expression of Vegf-a and disrupted retinal
      angiogenesis. In inflammation-induced angiogenesis in the rat cornea, systemic
      selective IKK2 inhibition decreased inflammatory cell invasion, suppressed CCL2,
      CXCL5, Cxcr2, and TNF-alpha expression and exhibited anti-angiogenic effects such
      as reduced limbal vessel dilation, reduced VEGF-A expression and reduced
      angiogenic sprouting, without noticeable toxic effect. In summary, targeting NF
      kappaB by selective IKK2 inhibition dampened the inflammatory and angiogenic
      responses in vivo by modulating the endothelial cell expression profile and
      motility, thus indicating an important role of NF-kappaB signaling in the
      development of pathologic corneal neovascularization.

PMID- 29332243
TI  - Photosystem I with benzoquinone analogues incorporated into the A1 binding site.
AB  - Time-resolved FTIR difference spectroscopy has been used to study photosystem I
      (PSI) particles with three different benzoquinones [plastoquinone-9 (PQ), 2,6
      dimethyl-1,4-benzoquinone (DMBQ), 2,3,5,6-tetrachloro-1,4-benzoquinone (Cl4BQ)]
      incorporated into the A1 binding site. If PSI samples are cooled in the dark to
      77 K, the incorporated benzoquinones are shown to be functional, allowing the
      production of time-resolved (P700+A1--P700A1) FTIR difference spectra. If samples
      are subjected to repetitive flash illumination at room temperature prior to
      cooling, however, the time-resolved FTIR difference spectra at 77 K display
      contributions typical of the P700 triplet state (3P700), indicating a loss of
      functionality of the incorporated benzoquinones, that occurs because of double
      protonation of the incorporated benzoquinones. The benzoquinone protonation
      mechanism likely involves nearby water molecules but does not involve the
      terminal iron-sulfur clusters FA and FB. These results and conclusions resolve
      discrepancies between results from previous low-temperature FTIR and EPR studies
      on similar PSI samples with PQ incorporated.

PMID- 29332244
TI  - Structural insights into the function of Elongator.
AB  - Conserved from yeast to humans, Elongator is a protein complex implicated in
      multiple processes including transcription regulation, alpha-tubulin acetylation,
      and tRNA modification, and its defects have been shown to cause human diseases
      such as familial dysautonomia. Elongator consists of two copies of six core
      subunits (Elp1, Elp2, Elp3, Elp4, Elp5, and Elp6) that are organized into two
      subcomplexes: Elp1/2/3 and Elp4/5/6 and form a stable assembly of ~ 850 kDa in
      size. Although the catalytic subunit of Elongator is Elp3, which contains a
      radical S-adenosyl-L-methionine (SAM) domain and a putative histone
      acetyltransferase domain, the Elp4/5/6 subcomplex also possesses ATP-modulated
      tRNA binding activity. How at the molecular level, Elongator performs its
      multiple functions and how the different subunits regulate Elongator's activities
      remains poorly understood. Here, we provide an overview of the proposed functions
      of Elongator and describe how recent structural studies provide new insights into
      the mechanism of action of this multifunctional complex.

PMID- 29332246
TI  - An historical perspective of the discovery of titin filaments -Part 2.
AB  - In 2017, a Special Issue of Biophysical Reviews was devoted to "Titin and Its
      Binding Partners. The issue contained a review: "An historical perspective of the
      discovery of titin filaments" by dos Remedios and Gilmour that was intended to be
      a history of the discovery of the giant protein titin, previously named
      connectin. The review took readers back to the earliest discovery of the so
      called third filament component of skeletal and cardiac muscle sarcomeres and
      ended in 1969. Recently, my colleague Shin'ichi Ishiwata gently reminded me of
      two papers published in 1990 and 1993 that were unwittingly omitted from the
      original historical perspective. In the first paper (J Cell Biol 110:53-62,
      1990), Funatsu et al. examined the elastic filaments in skeletal muscle using a
      combination of light and electron microscopy, but they also measured resting as
      well as passive stiffness mechanical measurements to establish that connectin
      (titin) is responsible for both stiffness and fiber tension. In the second paper
      (J Cell Biol 120:711-724, 1993), Funatsu et al. used permeabilised cardiac muscle
      myocytes (from rabbit papillary muscles) and focussed on filament ultrastructure
      using either freeze-substitution or deep-etched replica methods to visualise
      connectin/titin filaments in fibers with and without actin and myosin filaments.

PMID- 29332247
TI  - Practical advantages of contrast-enhanced ultrasound in abdominopelvic radiology.
AB  - Computed tomography (CT) and magnetic resonance imaging (MRI) are two of the
      workhorse modalities of abdominopelvic radiology. However, these modalities are
      not without patient- and technique-specific limitations that may prevent a timely
      and accurate diagnosis. Contrast-enhanced ultrasound (CEUS) is an effective,
      rapid, and cost-effective imaging modality with expanding clinical utility in the
      United States. In this pictorial essay, we provide a case-based discussion
      demonstrating the practical advantages of CEUS in evaluating a variety of
      pathologies in which CT or MRI was precluded or insufficient. Through these
      advantages, CEUS can serve a complementary role with CT and MRI in comprehensive
      abdominopelvic radiology.

PMID- 29332245
TI  - Reprogramming the metabolome rescues retinal degeneration.
AB  - Metabolomics studies in the context of ophthalmology have largely focused on
      identifying metabolite concentrations that characterize specific retinal
      diseases. Studies involving mass spectrometry (MS) and nuclear magnetic resonance
      (NMR) spectroscopy have shown that individuals suffering from retinal diseases
      exhibit metabolic profiles that markedly differ from those of control
      individuals, supporting the notion that metabolites may serve as easily
      identifiable biomarkers for specific conditions. An emerging branch of
      metabolomics resulting from biomarker studies, however, involves the study of
      retinal metabolic dysfunction as causes of degeneration. Recent publications have
      identified a number of metabolic processes-including but not limited to glucose
      and oxygen metabolism-that, when perturbed, play a role in the degeneration of
      photoreceptor cells. As a result, such studies have led to further research
      elucidating methods for prolonging photoreceptor survival in an effort to halt
      degeneration in its early stages. This review will explore the ways in which
      metabolomics has deepened our understanding of the causes of retinal degeneration
      and discuss how metabolomics can be used to prevent retinal degeneration from
      progressing to its later disease stages.

PMID- 29332248
TI  - Performance of diffusion-weighted magnetic resonance imaging at 3.0T for early
      assessment of tumor response in locally advanced rectal cancer treated with
      preoperative chemoradiation therapy.
AB  - PURPOSE: The purpose of the article is to determine whether changes in apparent
      diffusion coefficient (ADC) values of locally advanced rectal cancer (LARC)
      obtained 2 weeks after the beginning of chemoradiation therapy (CRT) allow to
      predict treatment response and whether correlate with tumor histopathologic
      response. METHODS: Forty-three patients receiving CRT for LARC and 3.0T magnetic
      resonance imaging with diffusion-weighted sequences before treatment, 2 weeks
      during, and 8 weeks post the completion of CRT were included. ADC values were
      calculated at each time point and percentage of ADC changes at 2 weeks (DeltaADC
      during) and 8 weeks (DeltaADC post) were assessed. Data were correlated to
      surgical results and histopathologic tumor regression grade (TRG), according to
      Mandard's classification. ADC values and DeltaADCs of complete responders (CR;
      TRG1) and non-complete responders (non-CR; TRG 2-5) were compared. Receiver
      operating characteristic curve (ROC) analysis was used to assess diagnostic
      accuracy of DeltaADC for differentiating CR from non-CR. The correlation with TRG
      was investigated using Spearman's rank test. RESULTS: DeltaADC during and
      DeltaADC post were significantly higher in CR (33.9% and 57%, respectively)
      compared to non-CR (13.5% and 2.2%, respectively) group (p = 0.006 and p < 0.001,
      respectively). ROC analysis revealed the following diagnostic performances:
      DeltaADC during: AUC 0.78 (0.08), p = 0.004, cut-off 20.6% (sensitivity 75% and
      specificity 76.5%); DeltaADC post: AUC 0.94 (0.04), p <= 0.001, cut-off 22%
      (sensitivity 95% and specificity 82.4%). Significant moderate and good negative
      correlation was found between DeltaADC during and DeltaADC post and TRG (r = -
      0.418, p = 0.007; r = - 694, p <= 0.001, respectively). CONCLUSION: DeltaADC at 2
      weeks after the beginning of CRT is a reliable tool to early assess treatment
      response.

PMID- 29332249
TI  - Correlation of flow density, as measured using optical coherence tomography
      angiography, with structural and functional parameters in glaucoma patients.
AB  - PURPOSE: To evaluate the correlation between flow density, as measured by optical
      coherence tomography angiography (OCTA), and structural and functional parameters
      in patients with open-angle glaucoma. METHODS: Thirty-four eyes of 34 patients
      with open-angle glaucoma and 35 eyes of 35 healthy subjects were prospectively
      included in this study. OCTA was performed using RTVue XR Avanti with AngioVue.
      The macula was imaged with a 3 * 3 mm scan and the optic nerve head (ONH) with a
      4.5 * 4.5 mm scan. Visual field parameters [mean deviation (MD), pattern standard
      deviation (PSD) and visual field index (VFI)], Bruch's membrane opening minimal
      rim width (BMO-MRW), retinal nerve fiber layer thickness (RNFLT) and the
      stereometric parameters rim area, cup/disc area (HRT III, Heidelberg Retina
      Tomograph, Heidelberg Engineering) were tested for correlation with flow density
      data. RESULTS: The flow density (whole en face) in the retinal OCT angiograms
      (superficial: p = 0.01; deep: p = 0.005), in the radial peripapillary capillary
      network (p < 0.001) and in the OCT angiograms of the optic nerve head (p = 0.004)
      were significantly lower in the glaucoma group when compared with the control
      group. The flow density in the RPC network correlated significantly with all
      functional and structural parameters tested. The strongest correlation was found
      between the RPC flow density (inside disc) and the BMO-MRW (Spearman's
      correlation coefficient = 0.912, p < 0.001). CONCLUSIONS: Glaucoma patients
      showed a reduced ONH and macular perfusion when compared with healthy controls.
      The flow density as measured by OCTA correlated with structural damage and visual
      field loss in glaucoma patients. Non-invasive quantitative analyses of flow
      density using OCTA provide a new parameter describing a different aspect of
      glaucoma, which could be useful in clinical practice.

PMID- 29332250
TI  - The levels of 12 cytokines and growth factors in tears: hyperthyreosis vs
      euthyreosis.
AB  - PURPOSE: Simultaneous analyses of the contents and ratios of 12 cytokines and
      growth factors in single samples of human tears were performed, and the results
      were compared between a group of healthy subjects and a group of patients with
      Graves' hyperthyreosis (GH) without thyroid-associated orbitopathy (TAO).
      METHODS: Determinations and concentration measurements of interleukins (IL-2,
      IL4, IL-6, IL-8, IL-10, IL-1alpha, and IL-1beta) interferon (IFN-gamma), tumor
      necrosis factor (TNF-alpha), monocyte chemoattractant protein (MCP-1), vascular
      endothelial growth factor (VEGF), and epidermal growth factor (EGF) were
      performed with single tear samples from 21 patients with hyperthyreosis and 22
      healthy subjects. The analyses were performed using a Randox microchip with an
      Evidence Biochip Array Analyzer. RESULTS: We found significant differences
      between the healthy donor group and the hyperthyreosis group in the levels of IL
      6, IL-10, VEGF, IL-1alpha, and MCP-1. The concentration of IL-6 was considerably
      higher in the hyperthyreosis group, IL-10 was higher in the healthy donor group,
      and VEGF and MPC-1 were higher in the hyperthyreosis group. The IL-8 and IFN
      gamma levels were higher in the hyperthyreosis group. The ratios of all of the
      cytokines to anti-inflammatory IL-10 were significantly elevated in the
      hyperthyreosis group. CONCLUSION: There are clear differences in the levels of
      cytokines and growth factors in the tears of healthy subjects and patients with
      GH without TAO. Tear cytokine changes and related dysfunctional tear syndrome
      (DTS) could be an early sign of occult TAO in Graves' hyperthyreosis patients.

PMID- 29332251
TI  - Clinical Pharmacokinetics and Pharmacodynamics of Telavancin Compared with the
      Other Glycopeptides.
AB  - Telavancin was discovered by modifying the chemical structure of vancomycin and
      belongs to the group of lipoglycopeptides. It employs its antimicrobial potential
      through two distinct mechanisms of action: inhibition of bacterial cell wall
      synthesis and induction of bacterial membrane depolarization and
      permeabilization. In this article we review the clinically relevant
      pharmacokinetic and pharmacodynamic data of telavancin. For comparison, the
      pharmacokinetic and pharmacodynamic data of the other glycopeptides are
      presented. Although, in contrast to the newer lipoglycopeptides, telavancin
      demonstrates a relatively short half-life and rapid total clearance, its apparent
      volume of distribution (Vd) is almost identical to that of dalbavancin. The
      accumulation of telavancin after repeated dosing is only marginal, whereas the
      pharmacokinetic values of the other glycopeptides show much greater differences
      after administration of multiple doses. Despite its high plasma-protein binding
      of 90% and relatively low Vd of approximately 11 L, telavancin shows near
      complete equilibration of the free fraction in plasma with soft tissue. The ratio
      of the area under the plasma concentration-time curve from time zero to 24 h
      (AUC24) of unbound plasma concentrations to the minimal inhibitory concentration
      (MIC) required to inhibit growth of 90% of organisms (MIC90) of Staphylococcus
      aureus and S. epidermidis of telavancin are sufficiently high to achieve
      pharmacokinetic/pharmacodynamic targets indicative for optimal bacterial killing.
      Considering both the AUC24/MIC ratios of telavancin and the near complete
      equilibration of the free fraction in plasma with soft tissue, telavancin is an
      appropriate antimicrobial agent to treat soft tissue infections caused by Gram
      positive pathogens. Although the penetration of telavancin into epithelial lining
      fluid (ELF) requires further investigations, the AUC24/MIC ratio for S. aureus
      indicates that bactericidal activity in the ELF could be expected.

PMID- 29332253
TI  - How to attract talented juniors to urogynaecology.

PMID- 29332252
TI  - A review of the impact of pregnancy and childbirth on pelvic floor function as
      assessed by objective measurement techniques.
AB  - The objective of this narrative review is to study the impact of pregnancy and
      childbirth on pelvic floor function as assessed by objective measurement
      techniques with quantitative data carried out during pregnancy and after
      childbirth. A literature search in MEDLINE and relevant and up-to-date journals
      from 1960 until April 2017 was performed for articles dealing with the impact of
      pregnancy and childbirth on pelvic floor function as assessed by objective
      measurement methods. Only studies describing objective measurement techniques.
      i.e., urodynamics, ultrasound (US), magnetic resonance imaging (MRI), Pelvic
      Organ Prolapse Quantification (POP-Q) system, and neurophysiologic tests carried
      out throughout pregnancy and after childbirth are included. Relevant studies
      presenting objective quantitative data are analyzed and briefly summarized. The
      number of studies meeting selection criteria was relatively few. Pregnancy,
      especially first pregnancy, is associated bladder neck lowering, increased
      bladder neck mobility, pelvic organ descent, decreased levator ani strength, and
      decreased urethral resistance. These changes are accentuated after vaginal
      delivery. Data on the impact of obstetrical and neonatal variables are transient
      and seem of less importance. Cesarean delivery is not completely protective. In
      most women, pelvic floor muscle function recovers in the year after delivery.
      Objective measurement techniques during pregnancy may allow identification of
      women susceptible to pelvic floor dysfunction later in life and offer the
      opportunity for counseling and preventive treatment strategies.

PMID- 29332255
TI  - Profiling attention and cognition enhancing drugs in a rat touchscreen-based
      continuous performance test.
AB  - RATIONALE: A novel rodent continuous performance test (CPT) was developed as one
      of the goals of the NEWMEDS (Novel Methods leading to New Medications in
      Depression and Schizophrenia) consortium to improve its translatability to the
      CPT test used in human subjects. OBJECTIVES: The objective of the study is to
      investigate the effects of attention and cognition enhancing drugs in rodent CPT.
      METHODS: A single cohort of rats were trained to asymptotic performance in the
      test. Pharmacological test sessions were then performed twice per week in a full
      crossover design with the following drugs tested: methylphenidate (0.3, 1, and 3
      mg/kg), the alpha4beta2 nicotinic agonist ABT-594 (0.0023, 0.007 and 0.023
      mg/kg), modafinil (8, 16, and 32 mg/kg), atomoxetine (0.3, 1, and 3 mg/kg),
      donepezil (0.1, 0.3, and 1 mg/kg), and memantine (1.25, 2.5, and 5 mg/kg).
      RESULTS: The stimulant-like drugs methylphenidate, ABT-594, and modafinil were
      found to increase measures of impulsivity and overall responding with generally
      no positive effects on d', a putative measure of attention, with the exception of
      ABT-594 which improved d' at the highest dose tested. Atomoxetine and the memory
      enhancing drugs donepezil and memantine, on the other hand, were found to reduce
      measures of impulsivity and responding and had either negligible or worsening
      effects on d'. CONCLUSIONS: Our results suggest rodent CPT can detect changes in
      impulsivity resulting from drugs known to improve attention in rodents and
      humans. However, additional work is needed to assess the sensitivity and validity
      of this assay for assessing effects on attention.

PMID- 29332254
TI  - Comparison of adjustable continence therapy periurethral balloons and artificial
      urinary sphincter in female patients with stress urinary incontinence due to
      intrinsic sphincter deficiency.
AB  - INTRODUCTION AND HYPOTHESIS: The objective was to compare the outcomes of the
      ACT(r) device with those of the artificial urinary sphincter (AUS) AMS 800 in the
      treatment of stress urinary incontinence (SUI) due to sphincter deficiency in
      women. METHODS: All the women who underwent surgical treatment for SUI due to
      intrinsic sphincter deficiency from 2007 to 2017 were included in a single-center
      retrospective study. The primary endpoint was the functional outcome.
      Perioperative functional parameters of the two groups were compared. RESULTS:
      Twenty-five patients underwent an ACT(r) implantation and 36 an AUS implantation.
      Patients in the AUS group were younger (62.9 vs 70.4 years; p = 0.03) with less
      comorbidity (ASA Score = 3 in 12.1% vs 33.3%; p = 0.005). Operative time and
      hospital stay were shorter in the ACT(r) group (45.7 vs 206.1 min; p < 0.001; 1.7
      vs 7 days; p < 0.001 respectively). There was a higher rate of intraoperative
      complications in the AUS group (47% vs 8%; p < 0.001) but the rates of
      postoperative complications were similar between both groups. The ACT(r) was
      associated with an increased risk of urinary retention (20% vs 2.8%; p = 0.04).
      Results were in favor of AUS for: decrease in USP stress incontinence subscore (
      7.6 vs -3.2; p < 0.001), number of pads per 24 h (- 4.6 vs -2.3; p = 0.002), PGII
      scale (PGII = 1: 61.1% vs 12%; p < 0.001), and cure rate (71.4% vs 21.7%; p <
      0.001). CONCLUSIONS: In the present series, keeping in mind the significantly
      different baseline characteristics, AUS implantation was associated with better
      functional outcomes than the ACT(r) in female patients with SUI due to intrinsic
      sphincter deficiency, but with a higher intraoperative complications rate, longer
      operative time, and a longer stay.

PMID- 29332256
TI  - Dopamine-dependent social information processing in non-human primates.
AB  - RATIONALE: Dopamine (DA) is a neurotransmitter whose roles have been suggested in
      various aspects of brain functions. Recent studies in rodents have reported its
      roles in social function. However, how DA is involved in social information
      processing in primates has largely remained unclear. OBJECTIVES: We investigated
      prefrontal cortical (PFC) activities associated with social vs. nonsocial visual
      stimulus processing. METHODS: Near-infrared spectroscopy (NIRS) was applied to
      Japanese macaques, along with pharmacological manipulations of DA transmission,
      while they were gazing at social and nonsocial visual stimuli. RESULTS:
      Oxygenated (oxy-Hb) and deoxygenated (deoxy-Hb) hemoglobin changes as well as
      functional connectivity based on such Hb changes within the PFC network which
      were distinct between social and nonsocial stimuli were observed. Administration
      of both D1 and D2 receptor antagonists affected the Hb changes associated with
      social stimuli, whereas D1, but not D2, receptor antagonist affected the Hb
      changes associated with nonsocial stimuli. CONCLUSIONS: These results suggest
      that mesocortical DA transmission in the PFC plays significant roles in social
      information processing, which involves both D1 and D2 receptor activation, in
      nonhuman primates. However, D1 and D2 receptor signaling in the PFC mediates
      different aspects of social vs. nonsocial information processing.

PMID- 29332259
TI  - Nobel Prizes 2017 and their impact for physiology.

PMID- 29332257
TI  - Kynurenic acid and its derivatives are able to modulate the adhesion and
      locomotion of brain endothelial cells.
AB  - The neuroprotective actions of kynurenic acid (KYNA) and its derivatives in
      several neurodegenerative disorders [characterized by damage to the cerebral
      endothelium and to the blood-brain barrier (BBB)] are well established. Cell
      extracellular matrix (ECM) adhesion is supposedly involved in recovery of
      impaired cerebral endothelium integrity (endothelial repair). The present work
      aimed to investigate the effects of KYNA and its synthetic derivatives on
      cellular behaviour (e.g. adhesion and locomotion) and on morphology of the GP8
      rat brain endothelial cell line, modeling the BBB endothelium. The effects of
      KYNA and its derivatives on cell adhesion were measured using an impedance-based
      technique, the xCELLigence SP system. Holographic microscopy (HolomonitorTM M4)
      was used to analyse both chemokinetic responses and morphometry. The GP8 cells
      proved to be a suitable model cell line for investigating cell adhesion and the
      locomotion modulator effects of kynurenines. KYNA enhanced cell adhesion and
      spreading, and also decreased the migration/motility of GP8 cells at
      physiological concentrations (10-9 and 10-7 mol/L). The derivatives containing an
      amide side-chain at the C2 position (KYNA-A1 and A2) had lower adhesion inducer
      effects compared to KYNA. All synthetic analogues (except KYNA-A5) had a time
      dependent inhibitory effect on GP8 cell adhesion at a supraphysiological
      concentration (10-3 mol/L). The immobilization promoting effect of KYNA and the
      adhesion inducer activity of its derivatives indicate that these compounds could
      contribute to maintaining or restoring the protective function of brain
      endothelium; they also suggest that cell-ECM adhesion and related cell responses
      (e.g. migration/motility) could be potential new targets of KYNA.

PMID- 29332258
TI  - Photodynamic antimicrobial chemotherapy (PACT) using toluidine blue inhibits both
      growth and biofilm formation by Candida krusei.
AB  - Among non-albicans Candida species, the opportunistic pathogen Candida krusei
      emerges because of the high mortality related to infections produced by this
      yeast. The Candida krusei is an opportunistic pathogen presenting an intrinsic
      resistance to fluconazol. In spite of the reduced number of infections produced
      by C. krusei, its occurrence is increasing in some groups of patients submitted
      to the use of fluconazol for prophylaxis. Photodynamic antimicrobial chemotherapy
      (PACT) is a potential antimicrobial therapy that combines visible light and a
      nontoxic dye, known as a photosensitizer, producing reactive oxygen species (ROS)
      that can kill the treated cells. The objective of this study was to investigate
      the effects of PACT, using toluidine blue, as a photosensitizer on both growth
      and biofilm formation by Candida krusei. In this work, we studied the effect of
      the PACT, using TB on both cell growth and biofilm formation by C. krusei. PACT
      was performed using a light source with output power of 0.068 W and peak
      wavelength of 630 nm, resulting in a fluence of 20, 30, or 40 J/cm2. In addition,
      ROS production was determined after PACT. The number of samples used in this
      study varied from 6 to 8. Statistical differences were evaluated by analysis of
      variance (ANOVA) and post hoc comparison with Tukey-Kramer test. PACT inhibited
      both growth and biofilm formation by C. krusei. It was also observed that PACT
      stimulated ROS production. Comparing to cells not irradiated, irradiation was
      able to increase ROS production in 11.43, 6.27, and 4.37 times, in the presence
      of TB 0.01, 0.02, and 0.05 mg/mL, respectively. These results suggest that the
      inhibition observed in the cell growth after PACT could be related to the ROS
      production, promoting cellular damage. Taken together, these results demonstrated
      the ability of PACT reducing both cell growth and biofilm formation by C. krusei.

PMID- 29332260
TI  - Prostate cancer rates in patients with initially negative elastography-targeted
      biopsy vs. systematic biopsy.
AB  - PURPOSE: To assess whether real-time elastography-targeted biopsy (RTE-bx) is
      superior to the standard systematic transrectal ultrasound (TRUS)-guided biopsy
      in predicting subsequent prostate cancer (PCa) rates in patients with initially
      negative biopsy and to specifically reveal differences in the occurrence of high
      grade (Gleason >= 4 + 3) PCa by comparing both biopsy methods. PATIENTS AND
      METHODS: Overall, 630 patients had an initially negative prostate biopsy between
      2007 and 2015, either RTE targeted (n = 213) or systematically (n = 417). Follow
      up data, ascertained by a questionnaire, of patients receiving RTE-bx were
      compared to data of patients receiving systematic biopsy (sbx) using Mann-Whitney
      U test and Chi-square test. We performed logistic regression analyses to assess
      any association with PCa or high-grade PCa occurrence. RESULTS: In total, 258
      (41%) patients were diagnosed with PCa at repeat biopsy whereof 54 (8.6%)
      harboured high-grade PCa. PCa occurred in 95 (44.6%) patients with initially
      negative RTE-bx and in 163 (39.1%) patients with initially negative sbx (p =
      0.003). 24 (11.3%) patients receiving RTE-bx and 30 (7.2%) patients receiving sbx
      were diagnosed with high-grade PCa (p = 0.095). Logistic regression analyses
      showed that patients with the initial RTE-bx vs. those with the initial sbx
      neither resulted in a significant higher risk for PCa occurrence (OR 1.35 [CI
      0.87-2.1]; p = 0.2) nor for high-grade PCa occurrence (OR 1.52 [CI 0.66-3.35]; p
      = 0.3). CONCLUSIONS: We found no statistically significant association of prior
      biopsy method to subsequent PCa or high-grade PCa occurrence. Referring to our
      analyses, RTE is not superior to sbx in predicting subsequent PCa rates and,
      therefore, not eligible to decide on repeat biopsy.

PMID- 29332261
TI  - Is the laser mightier than the sword? A comparative study for the urethrotomy.
AB  - PURPOSE: The knife is the most common used instrument for endoscopic urethrotomy.
      Unfortunately, there are high recurrence rates; it is thought that a laser
      reduces those rates. We compared the two techniques in this retrospective study.
      MATERIALS AND METHODS: Between 2010 and 2014, 127 patients were operated on with
      the knife (KG) and for 65 patients, the laser (LG) was used. We scored the
      complexity of the stricture using the UREThRAL stricture score (USS) and we
      scored if a treatment was successful. A failure was determined as recurrence, but
      also starting clean intermittent catheterization was stated as failure. RESULTS:
      There was no difference in USS between the two groups (KG: 5.7 vs LG: 6.0); the
      laser was more often used in a patient with a recurrence stricture (25.2 vs
      43.1%). No difference was found in postoperative increase in flow-rate (9.5 vs
      10.5 ml/sec), the number of complications (all Clavien I and one Clavien III in
      the KG) or the failure rate (58.3 vs 68.8%). When looked separately at patients
      treated for primary stricture and for a recurrence (96.7 vs 91.2%), no
      differences were found. CONCLUSION: There were no significant differences between
      knife and laser. With costs taken in consideration, we would advise treatment
      with the knife. Our results also show a high failure rate, especially in the
      recurrence group. Therefore, in case of recurrence, an open reconstruction should
      be considered.

PMID- 29332263
TI  - Creating a Primary Care Workforce: Strategies for Leaders, Clinicians, and
      Nurses.
AB  - Many primary care clinics struggle with rapid implementation and systematic
      expansion of primary care behavioral health (PCBH) services. Often, an uneven
      course of program development is due to lack of attention to preparing clinic
      leadership, addressing operational factors, and training primary care providers
      (PCPs) and nurses. This article offers competency tools for clinic leaders, PCPs,
      and nurses to use in assessing their status and setting change targets. These
      tools were developed by researchers working to disseminate evidence-based
      interventions in primary care clinics that included fully integrated behavioral
      health consultants and were then used by early adaptors of the PCBH model. By
      deploying these strategies, both practicing and teaching clinics will take a big
      step forward in developing the primary care workforce needed for primary care
      teams, where the behavioral health needs of a patient of any age can be addressed
      at the time of need.

PMID- 29332262
TI  - Tumor expression of survivin, p53, cyclin D1, osteopontin and fibronectin in
      predicting the response to neo-adjuvant chemotherapy in children with advanced
      malignant peripheral nerve sheath tumor.
AB  - PURPOSE: Selected cell-cycle regulators and extracellular matrix proteins were
      found to play roles in malignant peripheral nerve sheath tumor (MPNST) biology.
      We aimed to analyze whether initial tumor tissue expressions of survivin, p53,
      cyclin D1, osteopontin (OPN) and fibronectin (FN) correlate with the response to
      neo-adjuvant CHT (naCHT) in children with advanced inoperable MPNST. METHODS: The
      study included 26 children with MPNST (M/F 14/12, median age 130 months) treated
      in Polish centers of pediatric oncology between 1992 and 2013. Tissue expression
      of markers was studied immunohistochemically in the manually performed tissue
      microarrays and assessed semi-quantitatively as low and high, based on the rate
      of positive cells and staining intensity. RESULTS: Good response to naCHT was
      noted in 47.6%, while poor-in 52.4% of patients. The response to naCHT was
      influenced negatively by the presence of neurofibromatosis NF1 and high initial
      tumor tissue expression of OPN, survivin, p53 and cyclin D1. Patients with high
      tumor expression of either OPN, survivin or p53 and those with simultaneous high
      expression of >= 3 of the markers, responded significantly worse to naCHT, than
      patients, in whom expression of <= 2 markers were detected at diagnosis. Nearly,
      85% of patients expressing >= 3 markers, responded poor to CHT; while 87.5% of
      children, expressing <= 2 markers, were good responders. CONCLUSION: The initial
      tumor tissue expression of OPN, survivin, p53 and cyclin D1 may serve as markers
      to predict response to naCHT in pediatric advanced MPNST. Future studies in more
      numerous group of patients are needed to confirm these preliminary results.

PMID- 29332264
TI  - The Role of Affect and Coping in Diabetes Self-Management in Rural Adults with
      Uncontrolled Diabetes and Depressive Symptoms.
AB  - Many patients with diabetes have poorly controlled blood sugar levels and remain
      at risk for serious diabetes complications, despite access to effective diabetes
      treatments and services. Using the transactional model of stress and coping
      framework, the study investigated the contributions of affect (Positive and
      Negative Affect Schedule) and coping (maladaptive and adaptive coping from the
      Brief Cope) on diabetes self-management behaviors, namely diet and exercise. One
      hundred seventy-eight rural adults with uncontrolled diabetes and moderate
      depressive symptoms completed the measures. Multiple regression analyses
      demonstrated that positive affect and negative affect were significantly
      associated with diet and exercise, even after adjusting for diabetes severity,
      illness intrusiveness, and diabetes knowledge. However, two path analyses
      clarified that adaptive coping mediated the relationships between affect
      (positive and negative) and self-management behaviors (diet and exercise).
      Comprehensive diabetes treatments that include self-management support can assist
      patients in recognition and use of adaptive emotion-focused coping skills.

PMID- 29332266
TI  - Association Between the Interferon Gamma 874 T/A Polymorphism and the Severity of
      Valvular Damage in Patients with Rheumatic Heart Disease.
AB  - Interferon gamma (IFN-gamma) is a multifunctional cytokine that plays an
      important role in modulating almost all phases of the immune response and may be
      responsible for the increased valvular fibrosis and calcification in the
      pathogenesis of rheumatic heart disease (RHD). The aim of this study was to
      investigate the possible relationship between the IFN-gamma +874 T/A polymorphism
      and the severity of valvular damage in the Turkish population. The IFN-gamma
      genotypes were determined in 152 RHD patients and 151 healthy controls by ARMS
      PCR. Differences in genotype distribution between patients with RHD and control
      were evaluated by the chi2 test. All statistical analyses were performed with
      SPSS 15.0 Software program. Frequency of the AA genotype was found to be
      significantly lower and the TT genotype significantly higher in the RHD group
      compared to controls (p = 0.002 and p = 0.018, respectively). The TT genotype was
      found to be significantly higher (26.8% vs. 9.1%, p = 0.009) and the AA genotype
      significantly lower (29.1% vs. 8.2%, p = 0.001) in the severe valvular disease
      (SVD) group compared to mild valvular disease group. In the SVD group, 79
      patients had mitral balloon valvotomy and/or mitral valve replacement and had
      significantly higher TT genotype compared to patients with medical follow-up
      (30.4% vs. 19%, p = 0.001). The data demonstrated that TT genotype is associated
      with both RHD and the severity of RHD.

PMID- 29332267
TI  - IFN-lambda: A new spotlight in innate immunity against influenza virus infection.

PMID- 29332265
TI  - Review of a Parent's Influence on Pediatric Procedural Distress and Recovery.
AB  - Understanding how parents influence their child's medical procedures can inform
      future work to reduce pediatric procedural distress and improve recovery
      outcomes. Following a pediatric injury or illness diagnosis, the associated
      medical procedures can be potentially traumatic events that are often painful and
      distressing and can lead to the child experiencing long-term physical and
      psychological problems. Children under 6 years old are particularly at risk of
      illness or injury, yet their pain-related distress during medical procedures is
      often difficult to manage because of their young developmental level. Parents can
      also experience ongoing psychological distress following a child's injury or
      illness diagnosis. The parent and parenting behavior is one of many risk factors
      for increased pediatric procedural distress. The impact of parents on pediatric
      procedural distress is an important yet not well-understood phenomenon. There is
      some evidence to indicate parents influence their child through their own
      psychological distress and through parenting behavior. This paper has three
      purposes: (1) review current empirical research on parent-related risk factors
      for distressing pediatric medical procedures, and longer-term recovery outcomes;
      (2) consider and develop existing theories to present a new model for
      understanding the parent-child distress relationship during medical procedures;
      and (3) review and make recommendations regarding current assessment tools and
      developing parenting behavior interventions for reducing pediatric procedural
      distress.

PMID- 29332268
TI  - Methylmercury Intoxication Promotes Metallothionein Response and Cell Damage in
      Salivary Glands of Rats.
AB  - Environmental and occupational mercury exposure is considered a major public
      health issue. Despite being well known that MeHg exposure causes adverse effects
      in several physiologic functions, MeHg effects on salivary glands still not
      completely elucidated. Here, we investigated the cellular MeHg-induced damage in
      the three major salivary glands (parotid, submandibular, and sublingual) of adult
      rats after chronic, systemic and low doses of MeHg exposure. Rats were exposed by
      0.04 mg/kg/day over 60 days. After that, animals were euthanized and all three
      glands were collected. We evaluated total Hg accumulation, metallothionein I/II
      (MT I/II), alpha-smooth muscle actin (alpha-SMA), and cytokeratin 18 (CK18)
      immune expression. Our results have showed that MeHg is able to disrupt gland
      tissue and to induce a protective mechanism by MT I/II expression. We also showed
      that cell MT production is not enough to protect gland tissue against cellular
      structural damage seen by reducing marking of cytoskeletal proteins as CK18 and
      alpha-SMA. Our data suggest that chronic MeHg exposure in low-daily doses is able
      to induce cellular damage in rat salivary glands.

PMID- 29332270
TI  - Correction to: Hyper-response to Novelty Increases c-Fos Expression in the
      Hippocampus and Prefrontal Cortex in a Rat Model of Schizophrenia.
AB  - The original version of this article unfortunately contained a mistake. The
      spelling of the author Tommaso Ianniti was incorrect and has been corrected as
      Tommaso Iannitti. The original article has been corrected.

PMID- 29332269
TI  - Behavioral, Biochemical and Molecular Characterization of a Parkinson's Disease
      Mouse Model Using the Neurotoxin 2'-CH3-MPTP: A Novel Approach.
AB  - The neurotoxin MPTP has long been used to create a mouse model of Parkinson's
      disease (PD). Indeed, several MPTP analogues have been developed, including 2'
      CH3-MPTP, which was shown to induce nigrostriatal DA neuronal depletion more
      potently than MPTP. However, no study on behavioral and molecular alterations in
      response to 2'-CH3-MPTP has been carried out so far. In the present work, 2'-CH3
      MPTP was administered to mice (2.5, 5.0 and 10 mg/kg per injection, once a day, 5
      days) and histological, biochemical, molecular and behavioral alterations were
      evaluated. We show that, despite a dose-dependent-like pattern observed for
      nigrostriatal dopaminergic neuronal death and dopamine depletion, dose-specific
      alterations in dopamine metabolism and in the expression of dopaminergic
      neurotransmission-associated genes could be related to specific motor deficits
      elicited by the different doses tested. Interestingly, 2'-CH3-MPTP leads to
      increased DAT and MAO-B transcription, which could explain, respectively, its
      higher potency and the requirement of higher doses of MAO inhibitors to prevent
      nigrostriatal neuronal death when compared to MPTP. Also, perturbations in
      dopamine metabolism as well as possible alterations in dopamine bioavailability
      in the synaptic cleft were also identified and correlated with strength and
      ambulation deficits in response to specific doses. Overall, the present work
      brings new evidence supporting the distinct effects of 2'-CH3-MPTP when compared
      to its analogue MPTP. Moreover, our data highlight the utmost importance of a
      precise experimental design, as different administration regimens and doses yield
      different biochemical, molecular and behavioral alterations, which can be
      explored to study specific aspects of PD.

PMID- 29332271
TI  - Biodegradation of plastics: current scenario and future prospects for
      environmental safety.
AB  - Plastic is a general term used for a wide range of high molecular weight organic
      polymers obtained mostly from the various hydrocarbon and petroleum derivatives.
      There is an ever-increasing trend towards the production and consumption of
      plastics due to their extensive industrial and domestic applications. However, a
      wide spectrum of these polymers is non-biodegradable with few exceptions. The
      extensive use of plastics, lack of waste management, and casual community
      behavior towards their proper disposal pose a significant threat to the
      environment. This has raised growing concerns among various stakeholders to
      devise policies and innovative strategies for plastic waste management, use of
      biodegradable polymers especially in packaging, and educating people for their
      proper disposal. Current polymer degradation strategies rely on chemical,
      thermal, photo, and biological procedures. In the presence of proper waste
      management strategies coupled with industrially controlled biodegradation
      facilities, the use of biodegradable plastics for some applications such as
      packaging or health industry is a promising and attractive option for economic,
      environmental, and health benefits. This review highlights the classification of
      plastics with special emphasis on biodegradable plastics and their rational use,
      the identified mechanisms of plastic biodegradation, the microorganisms involved
      in biodegradation, and the current insights into the research on biodegradable
      plastics. The review has also identified the research gaps in plastic
      biodegradation followed by future research directions.

PMID- 29332272
TI  - Comparative study of selenium and selenium nanoparticles with reference to acute
      toxicity, biochemical attributes, and histopathological response in fish.
AB  - Recent studies have demonstrated that selenium (Se) and selenium nanoparticles
      (Se-NPs) exhibited toxicity at a higher concentration. The lethal concentration
      of Se and Se-NPs was estimated as 5.29 and 3.97 mg/L at 96 h in Pangasius
      hypophthalmus. However, the effect of different definite concentration of Se
      (4.5, 5.0, 5.5, and 6.0 mg/L) and Se-NPs (2.5, 3.0, 3.5, and 4.0 mg/L) was
      decided for acute experiment. Selenium and Se-NPs alter the biochemical
      attributes such as anti-oxidative status [catalase (CAT), superoxide dismutase
      (SOD), and glutathione-S-transferase (GST) activities], neurotransmitter enzyme,
      cellular metabolic enzymes, stress marker, and histopathology of P. hypophthalmus
      in a dose- and time-dependent manner. CAT, SOD, and GST were significantly
      elevated (p < 0.01) when exposed to Se and Se-NPs, and similarly, a
      neurotransmitter enzyme (acetylcholine esterase (AChE)) was significantly
      inhibited in a time- and dose-dependent manner. Further, aspartate
      aminotransferase, alanine aminotransferase, lactate dehydrogenase, and malate
      hydrogenase were noticeably (p < 0.01) affected by Se and Se-NPs from higher
      concentration to lower concentration. Stress markers such as cortisol and HSP 70
      were drastically enhanced by exposure to Se and Se-NPs. All the cellular
      metabolic and stress marker parameters were elevated which might be due to
      hyperaccumulation of Se and Se-NPs in the vital organ and target tissues. The
      histopathology of liver and gill was also altered such as large vacuole, cloudy
      swelling, focal necrosis, interstitial edema, necrosis in liver, and thickening
      of primary lamellae epithelium and curling of secondary lamellae due to Se and Se
      NP exposure. The study suggested that essential trace element in both forms
      (inorganic and nano) at higher concentration in acute exposure of Se and Se-NPs
      led to pronounced deleterious alteration on histopathology and cellular and
      metabolic activities of P. hypophthalmus.

PMID- 29332273
TI  - Pollution and ecological risk assessment of nutrients associated with deposited
      sediments collected from roof and road surfaces.
AB  - Surface-deposited sediment in urban areas is an essential environmental medium
      for assessing nutrient contamination. The total nitrogen (TN) and total
      phosphorus (TP) pollution associated with surface-deposited sediments can be
      transported into urban water bodies by runoff and can cause eutrophication of
      those water bodies. By analyzing the samples collected on roof surfaces and road
      surfaces, this study provides a comparison of the differences in TN and TP
      pollution loading in sediments on these two different impervious surface
      materials. Also, an assessment of the ecological risk of nutrients in surface
      deposited sediments with respect to grain size fraction was performed. The
      results indicate that the TN and TP pollution loading in both road-deposited
      sediments and roof-deposited sediments indicated an asymmetric "W" trend along
      with grain size fraction, and both road-deposited sediments and roof-deposited
      sediments had the highest TN and TP pollution contribution when the particle size
      is between 250 and 500 MUm. TN in roof-deposited sediments has high ecological
      risk when the particle size is less than 250 MUm. These findings help to provide
      guidance for the management of surface-deposited sediment pollution.

PMID- 29332275
TI  - Impact of drought stress induced by polyethylene glycol on growth, water
      relations and cell viability of Norway spruce seedlings.
AB  - We investigated physiological responses of 7-week-old Norway spruce seedlings to
      water deficits of different intensities. Hydroponically grown seedlings were
      subjected to mild (-0.15 MPa), strong (-0.5 and -1.0 MPa) and extreme (-1.5 MPa)
      water deficit induced by polyethylene glycol 6000, and their growth parameters,
      water status and physiological activity were analyzed. Seedlings effectively
      restricted water loss under drought, and even under extreme water deficit, shoot
      relative water content did not fall below 85%. Water stress induced substantial
      decreases in the osmotic potentials of root and needle cell sap, up to 0.3-0.4
      MPa under extreme water deficit, though this did not result from water loss or
      accumulation of K+ and Na+ ions. Seedling growth was very susceptible to water
      stress because of poor capacity for cell wall adjustment. Water stress injured
      seedling roots, as evidenced by the loss of root cell physiological activity
      estimated by the ability to hydrolyse fluorescein diacetate and by increased root
      calcium content up to 8-10-fold under extreme water stress. At the same time,
      root hair growth was enhanced, especially under mild water deficit, which
      increased the root water-absorbing capacity. In summary, seedlings of Norway
      spruce were characterized by high susceptibility to water stress and concurrently
      by pronounced ability to maintain water status. These characteristics are fully
      consistent with spruce confinement to moist habitats.

PMID- 29332274
TI  - Callitriche cophocarpa (water starwort) proteome under chromate stress: evidence
      for induction of a quinone reductase.
AB  - Chromate-induced physiological stress in a water-submerged macrophyte Callitriche
      cophocarpa Sendtn. (water starwort) was tested at the proteomic level. The
      oxidative stress status of the plant treated with 1 mM Cr(VI) for 3 days revealed
      stimulation of peroxidases whereas catalase and superoxide dismutase activities
      were similar to the control levels. Employing two-dimensional electrophoresis,
      comparative proteomics enabled to detect five differentiating proteins subjected
      to identification with mass spectrometry followed by an NCBI database search.
      Cr(VI) incubation led to induction of light harvesting chlorophyll a/b binding
      protein with a concomitant decrease of accumulation of ribulose bisphosphate
      carboxylase (RuBisCO). The main finding was, however, the identification of an
      NAD(P)H-dependent dehydrogenase FQR1, detectable only in Cr(VI)-treated plants.
      The FQR1 flavoenzyme is known to be responsive to oxidative stress and to act as
      a detoxification protein by protecting the cells against oxidative damage. It
      exhibits the in vitro quinone reductase activity and is capable of catalyzing two
      electron transfer from NAD(P)H to several substrates, presumably including
      Cr(VI). The enhanced accumulation of FQR1 was chromate-specific since other
      stressful conditions, such as salt, temperature, and oxidative stresses, all
      failed to induce the protein. Zymographic analysis of chromate-treated
      Callitriche shoots showed a novel enzymatic protein band whose activity was
      attributed to the newly identified enzyme. We suggest that Cr(VI)
      phytoremediation with C. cophocarpa can be promoted by chromate reductase
      activity produced by the induced quinone oxidoreductase which might take part in
      Cr(VI) -> Cr(III) bioreduction process and thus enable the plant to cope with the
      chromate-generated oxidative stress.

PMID- 29332276
TI  - Variability and reliability of POP concentrations in multiple breast milk samples
      collected from the same mothers.
AB  - Risk assessment of infant using a realistic persistent organic pollutant (POP)
      exposure through breast milk is essential to devise future regulation of POPs.
      However, recent investigations have demonstrated that POP levels in breast milk
      collected from the same mother showed a wide range of variation daily and
      monthly. To estimate the appropriate sample size of breast milk from the same
      mother to obtain reliable POP concentrations, breast milk samples were collected
      from five mothers living in Japan from 2006 to 2012. Milk samples from each
      mother were collected 3 to 6 times a day through 3 to 7 days consecutively. Food
      samples as the duplicated method were collected from two mothers during the
      period of breast milk sample collection. Those were employed for POP (PCBs, DDTs,
      chlordanes, and HCB) analysis. PCB concentrations detected in breast milk samples
      showed a wide range of variation which was maximum 63 and 60% of relative
      standard deviation (RSD) in lipid and wet weight basis, respectively. The time
      course trend of those variations among the mothers did not show any typical
      pattern. A larger amount of PCB intake through food seemed to affect 10 h after
      those concentrations in breast milk in lipid weight basis. Intraclass correlation
      coefficient (ICC) analyses indicated that the appropriate sample size for good
      reproducibility of POP concentrations in breast milk required at least two
      samples for lipid and wet weight basis.

PMID- 29332277
TI  - Efficient degradation of triclosan by an endophytic fungus Penicillium oxalicum
      B4.
AB  - Triclosan (TCS), a widely used antimicrobial and preservative agent, is an
      emerging contaminant in aqueous and soil environment. Microbial degradation of
      TCS has not been reported frequently because of its inhibition of microbe growth.
      To explore the new microbial resources for TCS biodegradation, fungal endophytes
      were isolated and screened for the degradation potential. The endophytic strain
      B4 isolated from Artemisia annua L. showed higher degradation efficiency and was
      identified as Penicillium oxalicum based on its morphology and ITS sequences of
      ribosomal DNA. In both medium and synthetic wastewater, TCS (5 mg/L) was almost
      completely degraded within 2 h by the strain B4. The high capacity of TCS uptake
      (127.60 +/- 8.57 mg/g dry weight, DW) of fungal mycelium was observed during the
      first 10 min after TCS addition. B4 rapidly reduced initial content (5.00 mg/L)
      of TCS to 0.41 mg/L in medium in 10 min. Then, the accumulation of TCS in
      mycelium was degraded from 0.45 to 0.05 mg/g DW after 1-h treatment. The
      degradation metabolites including 2-chlorohydroquinone, 2, 4-dichloropheno, and
      hydroquinone were found to be restrained in mycelia. The end products of the
      biodegradation in medium showed no toxicity to Escherichia coli. The new
      characteristics of high adsorption, fast degradation, and low residual toxicity
      highlight the potential of endophytic P. oxalicum B4 in TCS bioremediation.

PMID- 29332278
TI  - Exposure to nanoscale and microscale particulate air pollution prior to mining
      development near a northern indigenous community in Quebec, Canada.
AB  - This study serves as a baseline characterization of indoor and outdoor air
      quality in a remote northern indigenous community prior to the start of a major
      nearby mining operation, including measurements of nanoparticles, which has never
      been performed in this context before. We performed aerosol sample collection and
      real-time aerosol measurements at six different locations at the Cree First
      Nation of Waswanipi and the Montviel campsite, located 45 km west of the Cree
      First Nation of Waswanipi, in the south of the Nord-du-Quebec region. High
      concentrations of airborne nanoparticles (up to 3.98 * 104 +/- 8.9 * 103 cm-3 at
      64.9-nm midpoint particle diameter) and fine particles (up to 1.99 * 103 +/- 1.6
      * 102 cm-3 at 0.3-MUm midpoint particle diameter) were measured inside a
      residential home, where we did not find any ventilation or air filtration
      systems. The most abundant particle sizes by mass were between 0.19 and 0.55 MUm.
      The maximum concentration of analyzed heavy metals was detected at the d50 cut
      off particle size of 0.31 MUm; and the most abundant heavy metals in the aerosol
      samples were Al, Ba, Zn, Cu, Hg, and Pb. We concluded that the sources of the
      relatively high indoor particle concentrations were likely laundry machines and
      cooking emissions in the absence of a sufficient ventilation system. However, the
      chemical composition of particles resulting from mining activities is expected to
      be different from that of the aerosol particles from indoor sources. Installation
      and proper maintenance of sufficient ventilation and air filtration systems may
      reduce the total burden of disease from outdoor and indoor air pollution and
      remediate infiltrated indoor particulate pollution from the mining sources as
      well.

PMID- 29332279
TI  - Ecotoxicity thresholds for ametryn, diuron, hexazinone and simazine in fresh and
      marine waters.
AB  - Triazine and urea herbicides are two groups of photosystem II inhibiting
      herbicides frequently detected in surface, ground and marine waters. Yet, there
      are few water quality guidelines for herbicides. Ecotoxicity thresholds (ETs) for
      ametryn, hexazinone and simazine (triazine herbicides) and diuron (a urea
      herbicide) were calculated using the Australian and New Zealand method for
      deriving guideline values to protect fresh and marine ecosystems. Four ETs were
      derived for each chemical and ecosystem that should theoretically protect 99, 95,
      90 and 80% of species (i.e. PC99, PC95, PC90 and PC80, respectively). For all
      four herbicides, the phototrophic species were significantly more sensitive than
      non-phototrophic species, and therefore, only the former data were used to
      calculate the ETs. Comparison of the ET values to measured concentrations in 2606
      samples from 15 waterways that discharge to the Great Barrier Reef (2011-2015)
      found three exceedances of the simazine PC99, regular exceedances (up to 30%) of
      the PC99 in a limited number of rivers for ametryn and hexazinone and frequent (>
      40%) exceedances of the PC99 and PC95 ETs in at least four waterways for diuron.
      There were no exceedances of the marine ETs in inshore reef areas. Further,
      ecotoxicity data are required for ametryn and hexazinone to fresh and marine
      phototrophic species, for simazine to marine phototrophic species, for tropical
      phototrophic species, repeated pulse exposures and long-term (2 to 12 months)
      exposures to environmentally relevant concentrations.

PMID- 29332280
TI  - Hydrogeochemical processes and influence of seawater intrusion in coastal
      aquifers south of Chennai, Tamil Nadu, India.
AB  - Seawater intrusion promotes the salinity of groundwater, and it poses a great
      environmental impact on a global scale. The present study was carried out to
      determine the hydrogeochemical processes and influence of seawater intrusion in
      the coastal aquifers using geophysical, geochemical, and stable isotope
      techniques. The true resistivity value ranges from 0.5 to 8008.5 Omega-m which
      has been measured using vertical electrical sounding (VES) based on the
      Schlumberger method. About 33 groundwater samples were collected during post
      monsoon (POM) (January 2012) and pre-monsoon (PRM) (June 2012) seasons from open
      and bore wells and were analyzed for major ions and stable isotopes. EC, Na+, and
      Cl- were high in groundwater of wells near salt pan, the Buckingham Canal, and
      backwater regions. Around 45% of the groundwater of this study area is of Na+-Cl-
      type due to salinisation. Reverse ion exchange and silicate weathering are the
      dominant processes controlling the geochemistry of groundwater. Saturation
      indexes (SI) of halite (SIhalite) and gypsum (SIgypsum) versus sulfate show an
      increasing trend line from > 0 to < 0, which implies higher dissolution of
      minerals and hints increasing salinization during both seasons. The value of
      Na+/Cl- ranges between 0.7 and 2.4 (POM) and from 0.6 to 2.8 (PRM). The molar
      ratio suggested that around 25% of the groundwater samples are with values
      similar to those of seawater. Further, the groundwater is also affected by saline
      backwater, salt pan activities, and Buckingham Canal. Some locations are also are
      affected by anthropogenic, agricultural activities and geochemical processes.
      Heavy stable isotopes were found to be dominant in the coastal region due to
      seawater intrusion. Stable isotopes of delta18O range from - 5.6 to - 2.90/00
      during both periods. About 201 km2 of this area is affected by salinization. It
      is necessary to reduce pumping and plan for physical barriers to create
      freshwater ridges for controling the seawater intrusion.

PMID- 29332281
TI  - Programmed Cell Death in Plants: An Overview.
AB  - Programmed cell death (PCD) is a controlled mechanism that eliminates specific
      cells under developmental or environmental stimuli. All organisms-from bacteria
      to multicellular eukaryotes-have the ability to induce PCD in selected cells.
      Although this process was first identified in plants, the interest in deciphering
      the signaling pathways leading to PCD strongly increased when evidence came to
      light that PCD may be involved in several human diseases. In plants, PCD
      activation ensures the correct occurrence of growth and developmental processes,
      among which embryogenesis and differentiation of tracheary elements. PCD is also
      part of the defense responses activated by plants against environmental stresses,
      both abiotic and biotic.This chapter gives an overview of the roles of PCD in
      plants as well as the problems arising in classifying different kinds of PCD
      according to defined biochemical and cellular markers, and in comparison with the
      various types of PCD occurring in mammal cells. The importance of understanding
      PCD signaling pathways, with their elicitors and effectors, in order to improve
      plant productivity and resistance to environmental stresses is also taken into
      consideration.

PMID- 29332282
TI  - Investigation of Morphological Features of Autophagy During Plant Programmed Cell
      Death.
AB  - The investigation of autophagy particularly when observed during programmed cell
      death (PCD) is strongly based on the morphological features recorded with
      transmission electron microscope (TEM). Here we describe methods to induce and to
      inhibit autophagy in plants. Also some tips for obtaining better preservation of
      biological membranes, crucial for the investigation of autophagy, are provided
      together with information about plant autophagic mutants, use of antibodies and
      methods for 3D reconstruction of large membrane-bound objects that are commonly
      formed during autophagic processes leading to PCD in plants.

PMID- 29332283
TI  - Markers of Developmentally Regulated Programmed Cell Death and Their Analysis in
      Cereal Seeds.
AB  - Programmed cell death (PCD) is a key process for the development and
      differentiation of multicellular organisms, which is characterized by well
      defined morphological and biochemical features. These include chromatin
      condensation, DNA degradation and nuclear fragmentation, with nucleases and
      proteases playing a relevant function in these processes. In this chapter we
      describe methods routinely used for the analysis of hallmarks of developmentally
      regulated PCD in cereal seed tissues, which are based on agarose and
      polyacrylamide gel electrophoresis, in situ staining of DNA fragmentation, and
      cell-free assays of relevant enzymatic activities.

PMID- 29332284
TI  - Measurement of Hypersensitive Cell Death Triggered by Avirulent Bacterial
      Pathogens in Arabidopsis.
AB  - The hypersensitive response is one of the most powerful and complex defense
      reactions to survive to pathogen attacks during an incompatible plant-pathogen
      interaction. Local programmed cell death accompanies the hypersensitive response
      at the site of infection to prevent pathogen growth and spread. A precise
      quantitative assessment of this form of programmed cell death is essential to
      unravel the genetic and molecular mechanisms underlying the process. Here, we
      first describe the optimization of a Trypan Blue staining protocol for
      quantitatively measuring the HR-cell death in Arabidopsis. Furthermore, we
      provide an electrolyte leakage protocol based on pathogen vacuum infiltration,
      which allows its simultaneous application to a large number of plants as well as
      to Arabidopsis mutants affected by small size phenotype.

PMID- 29332285
TI  - Immunity-Associated Programmed Cell Death as a Tool for the Identification of
      Genes Essential for Plant Innate Immunity.
AB  - Plants have evolved a sophisticated innate immune system to contend with
      potential infection by various pathogens. Understanding and manipulation of key
      molecular mechanisms that plants use to defend against various pathogens are
      critical for developing novel strategies in plant disease control. In plants,
      resistance to attempted pathogen infection is often associated with
      hypersensitive response (HR), a form of rapid programmed cell death (PCD) at the
      site of attempted pathogen invasion. In this chapter, we describe a method for
      rapid identification of genes that are essential for plant innate immunity. It
      combines virus-induced gene silencing (VIGS), a tool that is suitable for
      studying gene function in high-throughput, with the utilization of immunity
      associated PCD, particularly HR-linked PCD as the readout of changes in plant
      innate immunity. The chapter covers from the design of gene fragment for VIGS,
      the agroinfiltration of the Nicotiana benthamian plants, to the use of immunity
      associated PCD induced by twelve elicitors as the indicator of activation of
      plant immunity.

PMID- 29332286
TI  - Analysis of Mitochondrial Markers of Programmed Cell Death.
AB  - Mitochondria play a crucial role in programmed cell death (PCD) in plants. In
      most cases of mitochondria-dependent PCD, cytochrome c (Cyt c) released from
      mitochondria due to the opening of mitochondrial permeability transition pore
      (MPTP) and the activation of caspase-like proteases. Here we describe the
      analytic methods of mitochondrial markers of PCD including mitochondria
      isolation, mitochondrial membrane permeability, mitochondrial inner membrane
      potential, Cytc release, ATP, and mitochondrial reactive oxygen species (ROS).

PMID- 29332287
TI  - Studying Retrograde Signaling in Plants.
AB  - Cellular homeostasis requires precise communication between various types of
      organelles. In particular, the communication between nucleus and semiautonomous
      organelles, mitochondria and chloroplasts, has received widespread attention.
      Communication from nucleus to other organelles is known as anterograde signaling,
      whereas communication from mitochondria or chloroplasts to the nucleus is known
      as retrograde signaling. Here we discuss methods used to study retrograde
      signaling in Arabidopsis thaliana. These methods may also be modified to study
      retrograde signaling in other plant species.

PMID- 29332288
TI  - ROS and Cell Death in Tomato Roots Infected by Meloidogyne Incognita.
AB  - Phytoparasitic nematodes are plant pests causing serious problems to a broad
      range of hosts, and Meloidogyne species are widely recognized as the most
      damaging among the root knot nematode groups. During the incompatible interaction
      between avirulent pathogens and resistant tomato cultivars, juvenile nematode
      invasions provoke a defense cascade, culminating in hypersensitive responses.
      Methods to detect the key molecules involved in oxidative metabolism of the
      infected tomato roots are described here.

PMID- 29332289
TI  - Detection of Reactive Oxygen and Nitrogen Species (ROS/RNS) During Hypersensitive
      Cell Death.
AB  - Reactive oxygen and nitrogen species (ROS/RNS) are signaling molecules involved
      in a plethora of physiological processes in plants. Especially, ROS and nitric
      oxide (NO) are key players that are required for programmed cell death (PCD). The
      PCD associated with the hypersensitive response (HR) has been well characterized
      and the role of H2O2 and NO as key signaling molecules inducing HR has been
      established. Localization of ROS and NO production in plant tissues in response
      to pathogens can be imaged by confocal laser microscopy by using specific
      fluorescent probes. Deciphering the time and spatial regulation of ROS and NO is
      very important to establish the cellular response of plants to adverse
      conditions. This chapter is mainly focused on the imaging of ROS and RNS
      accumulation in vivo in plant tissues undergoing PCD.

PMID- 29332291
TI  - Analysis of Reactive Carbonyl Species Generated Under Oxidative Stress.
AB  - Oxidation of membrane lipids by reactive oxygen species primarily generates lipid
      peroxides, from which various carbonyls, i.e., aldehydes and ketones, are formed.
      Among them, those with a carbonyl-conjugated C-C double bond have significant
      biological functions and are designated as reactive carbonyl species (RCS). A
      dozen kinds of RCS occurring in plant cells have a broad spectrum of reactivity
      and biological effects, depending on the structure. Several RCS have been
      recently found to activate caspase-like proteases in plants, thereby initiating
      PCD. Comprehensive and quantitative RCS analysis method using conventional HPLC
      is illustrated.

PMID- 29332290
TI  - DNA Diffusion Assay Applied to Plant Cells.
AB  - DNA diffusion assay is a simple, sensitive and reliable technique which allows
      the assessment of programmed cell death (PCD) or necrosis events based on nuclear
      morphology. It consists in isolating nuclei from plant material, which are then
      embedded in agarose and subjected to lysis in alkaline buffers. Under these
      conditions, and due to the presence of abundant alkali-labile sites in the DNA,
      small pieces of DNA diffuse in the agarose gel giving a specific halo appearance
      when stained with fluorescent dyes like DAPI (4',6-diamidino-2-phenylindole).
      Here, we describe an optimized protocol for DNA diffusion assay applied to
      different types of plant cells/tissues, indicating all the critical steps
      required for a successful experimental procedure.

PMID- 29332292
TI  - In Vivo Analysis of Calcium Levels and Glutathione Redox Status in Arabidopsis
      Epidermal Leaf Cells Infected with the Hypersensitive Response-Inducing Bacteria
      Pseudomonas syringae pv. tomato AvrB (PstAvrB).
AB  - Plants react to the attack of pathogen microorganisms by mounting appropriate and
      efficient downstream defense responses often involving a form of localized cell
      death called hypersensitive response (HR).Here we describe an innovative and
      noninvasive protocol based on in vivo bioimaging technique coupled with
      utilization of genetically encoded fluorescent sensors that allows to monitor and
      analyze intracellular calcium (Ca2+) dynamics and changes of the glutathione
      redox status taking place in plant organs during plant interaction with the HR
      inducing bacteria Pseudomonas syringae (PstAvrB).

PMID- 29332293
TI  - Measurement of Cyclic GMP During Plant Hypersensitive Disease Resistance
      Response.
AB  - Cyclic guanosine-3',5'-monophosphate (cGMP) is recognized as an important second
      messenger in plants, mediating intracellular signal in important physiological
      processes, including the hypersensitive disease resistance response induced by
      avirulent pathogens. In this context, the analysis of cGMP levels in infected
      plants requires an accurate and specific detection method allowing its
      quantification. Here, we describe an assay based on the Alphascreen technology,
      developed for animal cells and further adapted and optimized for the detection of
      cGMP in plants. The method is applied for the measurement of cGMP in Arabidopsis
      thaliana plants challenged with an avirulent strain of Pseudomonas syringae pv.
      tomato. This protocol includes the extraction of cGMP, the assay procedure and
      the calculation of cGMP concentration.

PMID- 29332294
TI  - Detection of MAPK3/6 Phosphorylation During Hypersensitive Response (HR)
      Associated Programmed Cell Death in Plants.
AB  - Programmed cell death (PCD) is an essential component of development, biotic and
      abiotic responses. Hypersensitive response (HR)-associated cell death activated
      under pathogen attack is one of the most dramatic manifestations of PCD in
      plants. Signal transduction through mitogen-activated protein kinase (MAPK)
      cascades, a very conserved signaling pathway across eukaryotes, is a core
      mediator for HR-associated PCD. Therefore, monitoring MAPK activation enables the
      mechanisms underlying HR-associated PCD to be elucidated. Here, we describe the
      use of a phosphorylation-specific MAPK3/6 antibody to monitor the activation of
      MAPK3/6 during HR-associated PCD. The technique may be adapted for use in other
      types of PCD.

PMID- 29332295
TI  - Measurement of the Caspase-1-Like Activity of Vacuolar Processing Enzyme in
      Plants.
AB  - Caspase-like activities are essential to regulate programed cell death in plants.
      Although no caspase orthologous enzymes with aspartic acid specificity have been
      identified in plants, vacuolar processing enzyme (VPE) exhibits a caspase-1-like
      activity. In this chapter, we introduce two methods for the measurement of the
      caspase-1-like/VPE activity. These methods are based on the cleavage of caspase-1
      specific synthetic substrates and on monitoring the active forms of VPE using a
      biotinylated-inhibitor blot analysis. Both methods are also adaptable to other
      plant caspase-like activities.

PMID- 29332296
TI  - Plant Cell Cultures as Model Systems to Study Programmed Cell Death.
AB  - The study of programmed cell death (PCD) activated in a certain group of cells is
      complex when analyzed in the whole plant. Plant cell suspension cultures are
      useful when investigating PCD triggered by environmental and developmental
      stimuli. Due to their homogeneity and the possibility to synchronize their
      responses induced by external stimuli, these cultures are used for studying the
      signaling pathways leading to PCD. The first problem in the analysis of PCD in
      cell cultures is the quantification of cell viability/death over time. Cultured
      cells from different plant species may have specific mitotic patterns leading to
      calli or cell chains mixed to single cell suspensions. For this reason, not all
      cell cultures allow morphological parameters to be investigated using microscopy
      analysis, and adapted or ad hoc methods are needed to test cell viability.Here we
      report on some accurate methods to establish and propagate cell cultures from
      different plant species, including crops, as well as to determine cell viability
      and PCD morphological and genetic markers. In particular, we describe a protocol
      for extracting nucleic acids required for real-time PCR analysis which has been
      optimized for those cell cultures that do not allow the use of commercial kits.

PMID- 29332297
TI  - Integrodifference equations in the presence of climate change: persistence
      criterion, travelling waves and inside dynamics.
AB  - To understand the effects that the climate change has on the evolution of species
      as well as the genetic consequences, we analyze an integrodifference equation
      (IDE) models for a reproducing and dispersing population in a spatio-temporal
      heterogeneous environment described by a shifting climate envelope. Our analysis
      on the IDE focuses on the persistence criterion, travelling wave solutions, and
      the inside dynamics. First, the persistence criterion, characterizing the global
      dynamics of the IDE, is established in terms of the basic reproduction number. In
      the case of persistence, a unique travelling wave is found to govern the global
      dynamics. The effects of the size and the shifting speed of the climate envelope
      on the basic reproduction number, and hence, on the persistence criterion, are
      also investigated. In particular, the critical domain size and the critical
      shifting speed are found in certain cases. Numerical simulations are performed to
      complement the theoretical results. In the case of persistence, we separate the
      travelling wave and general solutions into spatially distinct neutral fractions
      to study the inside dynamics. It is shown that each neutral genetic fraction
      rearranges itself spatially so as to asymptotically achieve the profile of the
      travelling wave. To measure the genetic diversity of the population density we
      calculate the Shannon diversity index and related indices, and use these to
      illustrate how diversity changes with underlying parameters.

PMID- 29332298
TI  - The ESS and replicator equation in matrix games under time constraints.
AB  - Recently, we introduced the class of matrix games under time constraints and
      characterized the concept of (monomorphic) evolutionarily stable strategy (ESS)
      in them. We are now interested in how the ESS is related to the existence and
      stability of equilibria for polymorphic populations. We point out that, although
      the ESS may no longer be a polymorphic equilibrium, there is a connection between
      them. Specifically, the polymorphic state at which the average strategy of the
      active individuals in the population is equal to the ESS is an equilibrium of the
      polymorphic model. Moreover, in the case when there are only two pure strategies,
      a polymorphic equilibrium is locally asymptotically stable under the replicator
      equation for the pure-strategy polymorphic model if and only if it corresponds to
      an ESS. Finally, we prove that a strict Nash equilibrium is a pure-strategy ESS
      that is a locally asymptotically stable equilibrium of the replicator equation in
      n-strategy time-constrained matrix games.

PMID- 29332299
TI  - Similarity search combined with docking and molecular dynamics for novel hAChE
      inhibitor scaffolds.
AB  - The main purpose of this study was to address the performance of virtual
      screening methods based on ligands and the protein structure of
      acetylcholinesterase (AChE) in order to retrieve novel human AChE (hAChE)
      inhibitors. In addition, a protocol was developed to identify novel hit compounds
      and propose new promising AChE inhibitors from the ZINC database with 10 million
      commercially available compounds. In this sense, 3D similarity searches using
      rapid overlay of chemical structures and similarity analysis through comparison
      of electrostatic overlay of docked hits were used to retrieve AChE inhibitors
      from collected databases. Molecular dynamics simulation of 100 ns was carried out
      to study the best docked compounds from similarity searches. Some key residues
      were identified as crucial for the dual binding mode of inhibitor with the
      interaction site. All results indicated the relevant use of EON and docking
      strategy for identifying novel hit compounds as promising potential
      anticholinesterase candidates, and seven new structures were selected as
      potential hAChE inhibitors. Graphical abstract Compound N01 in the 4M0E hAChE
      crystallography structure from docking results. Yellow dashed lines Hydrogen
      bonds, blue dashed lines pi-stacking interactions, green dashed lines cation-pi
      interactions.

PMID- 29332300
TI  - Long term exposure to cell phone frequencies (900 and 1800 MHz) induces
      apoptosis, mitochondrial oxidative stress and TRPV1 channel activation in the
      hippocampus and dorsal root ganglion of rats.
AB  - Mobile phone providers use electromagnetic radiation (EMR) with frequencies
      ranging from 900 to 1800 MHz. The increasing use of mobile phones has been
      accompanied by several potentially pathological consequences, such as
      neurological diseases related to hippocampal (HIPPON) and dorsal root ganglion
      neuron (DRGN). The TRPV1 channel is activated different stimuli, including CapN,
      high temperature and oxidative stress. We investigated the contribution TRPV1 to
      mitochondrial oxidative stress and apoptosis in HIPPON and DRGN following long
      term exposure to 900 and 1800 MHz in a rat model. Twenty-four adult rats were
      equally divided into the following groups: (1) control, (2) 900 MHz, and (3) 1800
      MHz exposure. Each experimental group was exposed to EMR for 60 min/ 5 days of
      the week during the one year. The 900 and 1800 MHz EMR exposure induced increases
      in TRPV1 currents, intracellular free calcium influx (Ca2+), reactive oxygen
      species (ROS) production, mitochondrial membrane depolarization (JC-1),
      apoptosis, and caspase 3 and 9 activities in the HIPPON and DRGN. These
      deleterious processes were further increased in the 1800 MHz experimental group
      compared to the 900 MHz exposure group. In conclusion, mitochondrial oxidative
      stress, programmed cell death and Ca2+ entry pathway through TRPV1 activation in
      the HIPPON and DRGN of rats were increased in the rat model following exposure to
      900 and 1800 MHz cell frequencies. Our results suggest that exposure to 900 and
      1800 MHz EMR may induce a dose-associated, TRPV1-mediated stress response.

PMID- 29332301
TI  - Evaluating Risk Tolerance from a Systematic Review of Preferences: The Case of
      Patients with Psoriasis.
AB  - BACKGROUND: Stated-preference methods have been widely used to evaluate patient
      relative preferences for the benefits and potential harms of psoriasis
      treatments. However, risk tolerance measures for treatment-related harms, a
      corollary of preferences, are rare despite their critical role in shared decision
      making and regulatory benefit-risk evaluations. This article presents a method to
      enhance information on patient risk tolerance through previously published
      preference results. OBJECTIVE: The objective of this article was to conduct the
      first meta-analysis of preferences to characterize the distribution of patients'
      maximum acceptable risk of harms associated with psoriasis treatments. DATA
      SOURCES: Maximum acceptable risks for treatment-related adverse events were
      extracted or derived from preference results published between 2011 and 2017.
      SYNTHESIS METHODS: Four different analyses were conducted to evaluate maximum
      acceptable risk information across studies: (1) listing of maximum acceptable
      risk values, (2) naive aggregation of maximum acceptable risks, (3) estimation of
      maximum acceptable risk mother distribution, and (4) random-effect regression
      analysis of maximum acceptable risks. RESULTS: Nine publications with maximum
      acceptable risk results, or with enough information to derive maximum acceptable
      risks, were identified from the search and screening of preference studies. The
      most commonly evaluated treatment benefits were duration of benefits, percentage
      and probability of improvement, and reductions in the coverage of lesions. The
      adverse-event risks most often included in the publications were those commonly
      associated with biologics, such as serious infections and malignancies. As
      expected, maximum acceptable risks changed with treatment benefits and treatment
      related adverse events. CONCLUSIONS: The results confirm the feasibility of using
      previously published preference information to characterize patient risk
      tolerance. The estimated distributions of maximum acceptable risk provide a
      benchmark against which future results can be compared, and signal gaps in our
      understanding of risk tolerance for specific health outcomes.

PMID- 29332302
TI  - Preoperative Cognitive Impairment As a Predictor of Postoperative Outcomes in a
      Collaborative Care Model.
AB  - OBJECTIVES: To compare postoperative outcomes of individuals with and without
      cognitive impairment enrolled in the Perioperative Optimization of Senior Health
      (POSH) program at Duke University, a comanagement model involving surgery,
      anesthesia, and geriatrics. DESIGN: Retrospective analysis of individuals
      enrolled in a quality improvement program. SETTING: Tertiary academic center.
      PARTICIPANTS: Older adults undergoing surgery and referred to POSH (N = 157).
      MEASUREMENTS: Cognitive impairment was defined as a score less than 25 out of 30
      (adjusted for education) on the St. Louis University Mental Status (SLUMS)
      Examination. Median length of stay (LOS), mean number of postoperative
      complications, rates of postoperative delirium (POD, %), 30-day readmissions (%),
      and discharge to home (%) were compared using bivariate analysis. RESULTS:
      Seventy percent of participants met criteria for cognitive impairment (mean SLUMS
      score 20.3 for those with cognitive impairment and 27.7 for those without).
      Participants with and without cognitive impairment did not significantly differ
      in demographic characteristics, number of medications (including anticholinergics
      and benzodiazepines), or burden of comorbidities. Participants with and without
      cognitive impairment had similar LOS (P = .99), cumulative number of
      complications (P = .70), and 30-day readmission (P = .20). POD was more common in
      those with cognitive impairment (31% vs 24%), but the difference was not
      significant (P = .34). Participants without cognitive impairment had higher rates
      of discharge to home (80.4% vs 65.1%, P = .05). CONCLUSION: Older adults with and
      without cognitive impairment referred to the POSH program fared similarly on most
      postoperative outcomes. Individuals with cognitive impairment may benefit from
      perioperative geriatric comanagement. Questions remain regarding the validity of
      available measures of cognition in the preoperative period.

PMID- 29332304
TI  - The i3S initiative: a Portuguese blend of Research and Innovation.

PMID- 29332303
TI  - Mitochondrial DNA, nuclear context, and the risk for carcinogenesis.
AB  - The inheritance of mitochondrial DNA (mtDNA) from mother to child is complicated
      by differences in the stability of the mitochondrial genome. Although the germ
      line mtDNA is protected through the minimization of replication between
      generations, sequence variation can occur either through mutation or due to
      changes in the ratio between distinct genomes that are present in the mother
      (known as heteroplasmy). Thus, the unpredictability in transgenerational
      inheritance of mtDNA may cause the emergence of pathogenic mitochondrial and
      cellular phenotypes in offspring. Studies of the role of mitochondrial metabolism
      in cancer have a long and rich history, but recent evidence strongly suggests
      that changes in mitochondrial genotype and phenotype play a significant role in
      the initiation, progression and treatment of cancer. At the intersection of these
      two fields lies the potential for emerging mtDNA mutations to drive
      carcinogenesis in the offspring. In this review, we suggest that this facet of
      transgenerational carcinogenesis remains underexplored and is a potentially
      important contributor to cancer. Environ. Mol. Mutagen., 2018. (c) 2018 Wiley
      Periodicals, Inc.

PMID- 29332305
TI  - Oblique thyroarytenoid muscle in humans: An independent muscle or an accessory
      belly?
AB  - OBJECTIVES/HYPOTHESIS: This study aimed to determine the prevalence and
      morphological variations of the oblique thyroarytenoid (TA) muscle in humans.
      STUDY DESIGN: Cadaveric anatomic dissections. METHODS: One hundred hemilarynges
      from 50 formalin-embalmed cadavers were dissected to investigate the morphology
      of muscle fibers of the TA muscle. RESULTS: Thirty-six (36%) hemilarynges were
      found to have a distinct oblique belly superficial to the TA muscle. In 28 cases,
      the belly had a relatively constant origin and an insertion that extended
      straight onto the TA muscle from the anterosuperior area of the internal surface
      of the thyroid lamina to the base of the muscular process of the arytenoid
      cartilage. Eight cases were located in a similar area but with some differences
      in the origin or insertion features. CONCLUSIONS: We proposed that the oblique TA
      muscle has a high prevalence and probably acts to close and relax the vocal
      cords. It remains to be determined whether the oblique TA muscle is an
      independent muscle or an accessory belly of the main TA muscle. LEVEL OF
      EVIDENCE: NA. Laryngoscope, 128:1634-1638, 2018.

PMID- 29332306
TI  - Current work environments: What problems are being faced by Japanese urologists?
AB  - Computer technology has contributed to innovative progress in industrial
      infrastructures and has had a major influence on various work environments.
      Evaluations of work environments are routinely carried out in Western countries,
      but historically there has been resistance to such evaluations in Japan. In this
      mini-review, we discuss the current work environments of urologists in Japan. The
      number of urologists has increased each year, and the population density of
      urologists was 5.4 (per 100 000 people) in 2014. The average age of urologists in
      Japan was 48.9 years, and the percentage of female urologists was just 5.3%.
      Additionally, the geographic distribution of urologists was uneven in Japan. From
      projections based on population dynamics, the need for more urologists in the
      near future will probably increase. Because medical environments vary depending
      on the country, it is necessary to understand current work environments in
      greater detail initially. Furthermore, we should determine original measures for
      the establishment of satisfactory urological work environments in Japan.

PMID- 29332307
TI  - Scaffold thrombosis following implantation of the ABSORB BVS in routine clinical
      practice: Insight into possible mechanisms from optical coherence tomography.
AB  - OBJECTIVES: To identify potential underlying mechanisms of early and (very) late
      scaffold thrombosis (ScT) by optical coherence tomography (OCT), in a frame-by
      frame analysis. BACKGROUND: The absorb scaffold is associated with an increased
      risk of ScT compared with metallic stents. Several potential causes of
      bioresorbable ScT have been identified, however the precise etiology still
      remains unclear. METHODS: Between February 2013 and February 2016, 13 patients
      presenting with definite ScT underwent OCT imaging. After guidewire passage or
      balloon inflations, OCT images were acquired. Pullbacks were assessed offline at
      each 1 mm longitudinal interval within the treated segment and the 5 mm segments
      adjacent to both edges. Primary cause of ScT was assessed by reviewing medical
      records, baseline angiographic films, and OCT pullback and angiographic films at
      time of ScT. RESULTS: 13 patients, with 14 thrombotic lesions presented either
      with early ScT (i.e., <=30 days) or very (late) (i.e., >30 days). Analysis
      demonstrated a significantly smaller in-scaffold maximal lumen diameter in the
      early cases (2.75 +/- 0.85 mm vs. 3.00 +/- 0.46 mm; P = 0.033) and a
      nonsignificant smaller minimal scaffold diameter (2.44 +/- 0.62 mm vs. 2.58 +/-
      0.37 mm P = 0.097). Per-strut analysis demonstrated significantly more malapposed
      scaffold struts in (very) late cases (6% versus 0.6%, P < 0.001). Assessment of
      the predominate cause showed underexpansion as the dominant factor in the early
      cases, while malapposition was predominantly seen in the (very)late cases.
      CONCLUSIONS: OCT performed in patients presenting with Absorb ScT demonstrated
      that malapposition of scaffold struts was more prominent in patients presenting
      with (very) late ScT, while underexpansion was more frequent in the early cases.

PMID- 29332308
TI  - Transcatheter closure of patent foramen ovale for secondary prevention of
      ischemic stroke: Quantitative synthesis of pooled randomized trial data.
AB  - OBJECTIVES: To evaluate the safety and efficacy of percutaneous device closure of
      patent foramen ovale (PFO) for secondary prevention of ischemic stroke
      BACKGROUND: Stroke remains the leading cause of serious long-term disability in
      the United States. The effectiveness of a percutaneous PFO closure in the
      prevention of recurrent cryptogenic strokes has not been established. METHODS: We
      performed a literature search using PubMed, EMBASE, Cochrane Central Register of
      Controlled Trials, Google Scholar, and Internet-based sources from January 2003
      to September 2017. Randomized controlled trails (RCTs) comparing percutaneous PFO
      closure to medical therapy alone. RESULTS: Five RCTs (CLOSURE I, PC Trial,
      REDUCE, RESPECT, and CLOSE) with 1,829 patients in the device group and 1,611
      patients in the medical group met inclusion criteria. The cumulative incidence of
      recurrent stroke was 2.02% in the PFO closure arm and 4.4% in the medical therapy
      group (RR 0.42, 95%CI 0.20, 0.91; P = 0.03). There was no difference in the
      incidence of death [0.7% vs. 0.9%; RR 0.76 (95% CI 0.35, 1.64), P = 0.49] or
      adverse events during the follow-up period [24.6% vs. 23.7% (RR 1.03; 95% CI
      0.91, 1.16), P = 0.65] between the closure and medical therapy groups. Incidence
      of atrial fibrillation was significantly higher in closure group compared to
      medical therapy [4% vs. 0.6% (RR 4.73; 95% CI 2.09, 10.70), P = 0.0002]. The
      comparative effectiveness of PFO closure (compared to medical therapy) was
      significantly more pronounced in those younger than 45 years, males, larger
      shunts and disc design platforms (P < 0.05). CONCLUSIONS: Based on the results of
      this analysis of randomized trial data, percutaneous PFO closure appears to be a
      safe and effective therapeutic option for the secondary prevention of ischemic
      stroke in patients with PFO and cryptogenic stroke.

PMID- 29332309
TI  - How leaves of mycoheterotrophic plants evolved - from the view point of a
      developmental biologist.
AB  - How mycoheterotrophs have evolved and how they are sustained are enigmas.
      Structural analyses of the plastid genome and phylogenetic analyses of
      mycoheterotrophs have been used to identify mycorrhizal fungi. Molecular genetic
      studies have also revealed the mechanism for plant-fungi interactions. However,
      the evolution of the small, scale-like vegetative leaves of mycoheterotrophs is
      unknown. As almost all genes determining leaf size affect the floral organ sizes,
      it is highly implausible that loss-of-function mutations in leaf size regulators
      caused the evolution of smaller foliage leaves in mycoheterotrophs. In this
      Viewpoint, possible evolutionary scenarios of scale-like leaves in
      mycoheterotrophs are discussed from the perspective of developmental genetics of
      leaves in model plants, including: vegetative phase-specific changes in
      expression of leaf size regulator(s); the change from foliage leaves to scale
      like lateral organs; and expression of suppressor(s) involved in organ
      development. These possibilities can be tested in future studies. This approach
      will provide a new research field in the developmental biology of plants.

PMID- 29332310
TI  - Advances and current challenges in calcium signaling.
AB  - Content Summary 414 I. Introduction 415 II. Ca2+ importer and exporter in plants
      415 III. The Ca2+ decoding toolkit in plants 415 IV. Mechanisms of Ca2+ signal
      decoding 417 V. Immediate Ca2+ signaling in the regulation of ion transport 418
      VI. Ca2+ signal integration into long-term ABA responses 419 VII Integration of
      Ca2+ and hormone signaling through dynamic complex modulation of the
      CCaMK/CYCLOPS complex 420 VIII Ca2+ signaling in mitochondria and chloroplasts
      422 IX A view beyond recent advances in Ca2+ imaging 423 X Modeling approaches in
      Ca2+ signaling 424 XI Conclusions: Ca2+ signaling a still young blooming field of
      plant research 424 Acknowledgements 425 ORCID 425 References 425 SUMMARY:
      Temporally and spatially defined changes in Ca2+ concentration in distinct
      compartments of cells represent a universal information code in plants. Recently,
      it has become evident that Ca2+ signals not only govern intracellular regulation
      but also appear to contribute to long distance or even organismic signal
      propagation and physiological response regulation. Ca2+ signals are shaped by an
      intimate interplay of channels and transporters, and during past years important
      contributing individual components have been identified and characterized. Ca2+
      signals are translated by an elaborate toolkit of Ca2+ -binding proteins, many of
      which function as Ca2+ sensors, into defined downstream responses. Intriguing
      progress has been achieved in identifying specific modules that interconnect Ca2+
      decoding proteins and protein kinases with downstream target effectors, and in
      characterizing molecular details of these processes. In this review, we reflect
      on recent major advances in our understanding of Ca2+ signaling and cover
      emerging concepts and existing open questions that should be informative also for
      scientists that are currently entering this field of ever-increasing breath and
      impact.

PMID- 29332311
TI  - Otolaryngology/head and neck region manifestations of Brucella.
AB  - OBJECTIVES/HYPOTHESIS: Patients with Brucella infection present with nonspecific
      symptoms originating from different organs. In this study, we investigated the
      manifestations involving principally the otolaryngology/head and neck region.
      STUDY DESIGN: Retrospective cohort chart review. METHODS: A retrospective
      analysis of patients diagnosed with brucellosis in a tertiary medical center.
      Medical records of 55 patients treated for positive Brucella blood cultures
      between 2007 and 2016 were analyzed. Clinical manifestations localized to the
      otolaryngology/head and neck region were evaluated. RESULTS: Most patients (78%)
      in our study group lived in rural areas. There was an almost equal gender
      distribution and a wide age range (2-77 years). Nonspecific symptoms, including
      fever (71%), fatigue (31%), weight loss (20%), and night sweats (32.7%) were the
      most common. Of the specific organ systems affected by Brucella, the
      osteoarthritic system was most commonly infected (45.5%). Three patients (5.5%)
      presented with predominantly localized otolaryngology/head and neck region
      symptoms, consisting of necrotic lymphadenopathy or a thyroid abscess. All
      patients underwent drainage procedures, and the diagnosis was confirmed by
      positive blood and pus cultures. Complete resolution was achieved with prolonged
      antibiotic treatment. CONCLUSIONS: Brucella infection should be suspected in
      patients with nonspecific constitutional symptoms associated with neck
      lymphadenopathy or thyroid abscess, especially in those living in rural areas. A
      high index of suspicion is mandatory for proper diagnosis and treatment. Formal
      drainage and prolonged antibiotic treatments are required. We strongly recommend
      simple drainage and not excision as the mainstay of surgical treatment. LEVEL OF
      EVIDENCE: 4. Laryngoscope, 128:2056-2059, 2018.

PMID- 29332312
TI  - Corrigendum.

PMID- 29332314
TI  - New year's greetings: International Journal of Urology celebrates 25 years.

PMID- 29332315
TI  - Comparison of treatment strategies for femoro-popliteal disease: A network meta
      analysis.
AB  - OBJECTIVES: We sought to compare treatment strategies in a Bayesian network meta
      analysis of randomized controlled trials. BACKGROUND: Peripheral artery disease
      (PAD) is a prevalent morbidity that is treated with various strategies. METHODS:
      We performed a MEDLINE search for randomized studies comparing at least 2
      treatment strategies, including bypass surgery, percutaneous transluminal
      angioplasty (PTA) balloons, stents, covered stents, drug-eluting stents (DES),
      and drug-coated balloons (DCB), in patients with native femoro-popliteal disease.
      Mixed treatment comparison model generation was performed to directly and
      indirectly compare the strategies in terms of restenosis and target lesion
      revascularization (TLR) presented as odds ratios (OR, [95% credible intervals]).
      RESULTS: Twenty-nine studies with 4,820 patients were included in the present
      study. PTA was the largest group with 1,900 patients, followed by DCB (n =
      1,343), bare metal stents (n = 941), covered stents (n = 304), DES (n = 236), and
      bypass (n = 92). Mean age was 68 +/- 9 years, 64% were male, 37% diabetic, and
      55% smokers. Mean lesion length was 77 +/- 44 mm, and 39% were total occlusions.
      Bayesian hierarchical random-effects model demonstrated all treatments were
      significantly better than, or had a trend toward superiority over, PTA, with DCB
      ranking well in both restenosis (OR = 0.29, [0.17-0.47]) and TLR (OR = 0.31,
      [0.20-0.46]). Nonetheless, none of the therapies showed superiority in terms of
      survival or amputations. CONCLUSION: Treatment of femoro-popliteal disease has
      significantly evolved in recent years, with higher rates of patency and freedom
      from TLR. However, the utility of these treatment strategies in terms of
      reduction of amputations and overall survival remains in question.

PMID- 29332316
TI  - How do I implement a whole blood program for massively bleeding patients?
AB  - Building on the successful military experience, interest has been rekindled in
      transfusing whole blood (WB) early in the resuscitation of traumatically injured
      civilians, often before their ABO group is known. WB efficiently provides
      treatment for shock and coagulopathy, as well as platelet hemostatic function, to
      patients losing large volumes of blood. Unlike group O uncrossmatched red blood
      cells (RBCs), group O WB contains a substantial amount of plasma, which is
      incompatible with the RBCs of all non-group O recipients. Thus, when implementing
      a WB program, it is important to decide how to mitigate the risk of immune
      mediated hemolysis. Other questions that a hospital needs to answer before
      implementing a WB program include determining which patients will be eligible for
      this product, how many units eligible patients can receive, for how long it
      should be stored and under what conditions, and how to monitor for adverse
      events. The donor center needs to consider if the WB should be leukoreduced, how
      to comply with the AABB's transfusion-related acute lung injury risk mitigation
      standard, and into which storage solution it should be collected. This report
      describes the multidisciplinary approach taken to implementing a civilian WB
      program at a multihospital health care system in the United States.

PMID- 29332317
TI  - Routine use of Day 6 and Day 7 platelets with rapid testing: two hospitals assess
      impact 1 year after implementation.
AB  - BACKGROUND: In March 2016 the US Food and Drug Administration published a draft
      guidance to enhance the safety of platelets (PLTs) for transfusion. Options for
      hospital transfusion services include the use of rapid testing to extend
      apheresis PLT dating for up to 7 days. This report describes the impact of
      routine use of Day 6 and Day 7 PLTs at two hospital transfusion services 1 year
      after implementation of rapid testing for outdate extension. STUDY DESIGN AND
      METHODS: PLT transfusion and inventory data were obtained from two hospital-based
      transfusion services for 12 months before and 12 months after implementation of
      rapid testing to extend the outdate of apheresis PLTs to 7 days. RESULTS: The
      outdate rate decreased from 5% to 2% (p < 0.0001) at Hospital 1 and 28% to 14% (p
      < 0.001) at Hospital 2 after implementation of routine use of Day 6 and Day 7
      PLTs. The proportion of apheresis PLT units that underwent secondary screening
      for bacterial contamination before transfusion in the postimplementation period
      increased from 33% to 54% at Hospital 1 and from 0% to 31% at Hospital 2.
      CONCLUSION: A significant decrease in outdate rate was observed after routine use
      of Day 6 and Day 7 PLTs. Use of rapid testing to extend PLT outdate also resulted
      in a larger proportion of PLTs that underwent secondary testing for bacterial
      contamination before transfusion. These observations demonstrate that use of
      rapid testing to extend apheresis PLT dating up to 7 days enhances the safety of
      PLTs for transfusion and decreases wastage of a limited resource.

PMID- 29332318
TI  - Intraspecific differences in plant defense induction by fall armyworm strains.
AB  - The underlying adaptive mechanisms by which insect strains are associated with
      specific plants are largely unknown. In this study, we investigated the role of
      herbivore-induced defenses in the host plant association of fall armyworm
      (Spodoptera frugiperda) strains. We tested the expression of herbivore-induced
      defense-related genes and the activity of plant-defensive proteins in maize and
      Bermuda grass upon feeding by fall armyworm strains. The rice strain caterpillars
      induced greater accumulation of proteinase inhibitors in maize than the corn
      strain caterpillars. In Bermuda grass, feeding by the corn strain suppressed
      induction of trypsin inhibitor activity whereas the rice strain induced greater
      activity levels. Differences in elicitation of these plant defenses by the two
      strains seems to be due to differences in the activity levels of the salivary
      enzyme phospholipase C. The levels of plant defense responses were negatively
      correlated with caterpillar growth, indicating a fitness effect. Our results
      indicate that specific elicitors in the saliva of fall armyworm stains trigger
      differential levels of plant defense responses that affect caterpillar growth and
      thus may influence host plant associations in field conditions. The composition
      and secretion of plant defense elicitors may have a strong influence in the host
      plant association of insect herbivores.

PMID- 29332319
TI  - Treatment of Latent Tuberculosis Infection and Its Clinical Efficacy.
AB  - The role of the treatment for latent tuberculosis infection (LTBI) has been
      underscored in the intermediate tuberculosis (TB) burden countries like South
      Korea. LTBI treatment is recommended only for patients at risk for progression to
      active TB-those with frequent exposure to active TB cases, and those with
      clinical risk factors (e.g., immunocompromised patients). Recently revised
      National Institute for Health and Care Excellence (NICE) guideline recommended
      that close contacts of individuals with active pulmonary or laryngeal TB, aged
      between 18 and 65 years, should undergo LTBI treatment. Various regimens for LTBI
      treatment were recommended in NICE, World Health Organization (WHO), and Centers
      for Disease Control and Prevention guidelines, and superiority of one recommended
      regimen over another was not yet established. Traditional 6 to 9 months of
      isoniazid (6H or 9H) regimen has an advantage of the most abundant evidence for
      clinical efficacy-60%-90% of estimated protective effect. However, 6H or 9H
      regimen is related with hepatotoxicity and low compliance. Four months of
      rifampin regimen is characterized by less hepatotoxicity and better compliance
      than 9H, but has few evidence of clinical efficacy. Three months of isoniazid
      plus rifampin was proved equivalence with 6H or 9H regimen in terms of efficacy
      and safety, which was recommended in NICE and WHO guidelines. The clinical
      efficacy of isoniazid plus rifapentine once-weekly regimen for 3 months was
      demonstrated recently, which is not yet introduced into South Korea.

PMID- 29332320
TI  - The Role of Tiotropium+Olodaterol Dual Bronchodilator Therapy in the Management
      of Chronic Obstructive Pulmonary Disease.
AB  - Bronchodilator therapy is central to the management of chronic obstructive
      pulmonary disease and are recommended as the preferred treatment by the Global
      Obstructive Lung Disease Initiative (GOLD). Long acting anti-muscarinics (LAMA)
      and long acting beta2 agonists (LABA) are both more effective than regular short
      acting drugs but many patients remain symptomatic despite monotherapy with these
      drugs. Combination therapy with LAMA and LABA increases the therapeutic benefit
      while minimizing dose-dependent side effects of long-acting bronchodilator
      therapy. The TOviTO programme has investigated the benefits of treatment with a
      combination of tiotropium and olodaterol administered via a single inhaler.
      Tiotropium+olodaterol 5/5 MUg significantly improved forced expiratory volume in
      1 second (FEV1) area under the curve from 0 to 3 hours, trough FEV1 health status
      and breathlessness versus the mono-components and placebo. Tiotropium+olodaterol
      5/5 MUg also increased endurance time and reduced dynamic hyperinflation during
      constant work rate cycle ergometry. On the basis of these and other studies the
      2017 GOLD report recommends escalating to dual bronchodilator therapy in patients
      in groups B and C if they remain symptomatic or continue to have exacerbations
      and as initial therapy for patients in group D.

PMID- 29332321
TI  - Indicators and Qualitative Assessment of Lung Cancer Management by Health
      Insurance Review and Assessment Service (HIRA) of Korea in 2015.
AB  - Cancer is the leading cause of death in the Republic of Korea and cancer death
      accounts for 27.8% of the total deaths, which is not only a social issue but also
      a concern for the public. Among the cancer death rates, lung cancer mortality
      account for 34 deaths per 100,000 populations, making it the number one cancer
      death rate. In a preliminary report on cancer death in 2012, the lung cancer
      mortality ratio showed the regional variation indicating that there were
      differences in the qualitative level and the structure among the medical care
      benefit agency and in the assessment of the treatment process. Therefore, the
      Health Insurance Review and Assessment Service (HIRA) had begun evaluation of the
      assessment of lung cancer treatment since 2014 to improve the quality of lung
      cancer care through evaluation and feeds back the results of lung cancer care
      process. In this report, authors described the current Indicators for the lung
      cancer adequacy assessment proposed by HIRA and results of the evaluation
      reported in 2017.

PMID- 29332322
TI  - Tumor Immunology and Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer.
AB  - Lung cancer is one of the most commonly diagnosed cancers and the leading cause
      of cancer-related deaths worldwide. Although progress in the treatment of
      advanced non-small cell lung cancer (NSCLC) has been made over the past decade,
      the 5-year survival rate in patients with lung cancer remains only 10%-20%.
      Obviously, new therapeutic options are required for patients with advanced NSCLC
      and unmet medical needs. Cancer immunotherapy is an evolving treatment modality
      that uses a patient's own immune systems to fight cancer. Theoretically, cancer
      immunotherapy can result in long-term cancer remission and may not cause the same
      side effects as chemotherapy and radiation. Immuno-oncology has become an
      important focus of basic research as well as clinical trials for the treatment of
      NSCLC. Immune checkpoint inhibitors are the most promising approach for cancer
      immunotherapy and they have become the standard of care for patients with
      advanced NSCLC. This review summarizes basic tumor immunology and the relevant
      clinical data on immunotherapeutic approaches, especially immune checkpoint
      inhibitors in NSCLC.

PMID- 29332323
TI  - Development of Prediction Equation of Diffusing Capacity of Lung for Koreans.
AB  - BACKGROUND: The diffusing capacity of the lung is influenced by multiple factors
      such as age, sex, height, weight, ethnicity and smoking status. Although a
      prediction equation for the diffusing capacity of Korea was proposed in the mid
      1980s, this equation is not used currently. The aim of this study was to develop
      a new prediction equation for the diffusing capacity for Koreans. METHODS: Using
      the data of the Korean National Health and Nutrition Examination Survey, a total
      of 140 nonsmokers with normal chest X-rays were enrolled in this study. RESULTS:
      Using linear regression analysis, a new predicting equation for diffusing
      capacity was developed. For men, the following new equations were developed:
      carbon monoxide diffusing capacity (DLco)=-10.4433-0.1434*age
      (year)+0.2482*heights (cm); DLco/alveolar volume (VA)=6.01507-0.02374*age (year)
      0.00233*heights (cm). For women the prediction equations were described as
      followed: DLco=-12.8895-0.0532*age (year)+0.2145*heights (cm) and DLco/VA=7.69516
      0.02219*age (year)-0.01377*heights (cm). All equations were internally validated
      by k-fold cross validation method. CONCLUSION: In this study, we developed new
      prediction equations for the diffusing capacity of the lungs of Koreans. A
      further study is needed to validate the new predicting equation for diffusing
      capacity.

PMID- 29332325
TI  - Is alpha-N-acetylgalactosaminidase the key to curing cancer? A mini-review and
      hypothesis.
AB  - In the constant battle against cancer cells, macrophages are of great importance.
      Their activation is achieved through various mechanisms such as Vitamin D binding
      protein (VDBP or Gc). After undergoing modifications via enzymes secreted by
      stimulated lymphocytes, VDBP is modified into Macrophages Activator Form/Factor
      (Gc-MAF). Some studies (particularly those focusing on cancer) have reported that
      an enzyme known as alpha-N-acetylgalactosaminidase (nagalase) facilitates the
      deglycosylation of Gc-MAF, which in turn inhibits the activation of macrophages.
      The aim of this review was to evaluate studies associated with nagalase and its
      escalation in various diseases and to propose hypothetical solutions in order to
      neutralize the effects of nagalase in cancer patients.

PMID- 29332324
TI  - Effects of Macrolide and Corticosteroid in Neutrophilic Asthma Mouse Model.
AB  - BACKGROUND: Asthma is a disease of chronic airway inflammation with heterogeneous
      features. Neutrophilic asthma is corticosteroid-insensitive asthma related to
      absence or suppression of TH2 process and increased TH1 and/or TH17 process.
      Macrolides are immunomodulatory drug that reduce airway inflammation, but their
      role in asthma is not fully known. The purpose of this study was to evaluate the
      role of macrolides in neutrophilic asthma and compare their effects with those of
      corticosteroids. METHODS: C57BL/6 female mice were sensitized with ovalbumin
      (OVA) and lipopolysaccharides (LPS). Clarithromycin (CAM) and/or dexamethasone
      (DXM) were administered at days 14, 15, 21, 22, and 23. At day 24, the mice were
      sacrificed. RESULTS: Airway resistance in the OVA+LPS exposed mice was elevated
      but was more attenuated after treatment with CAM+DXM compared with the
      monotherapy group (p<0.05 and p<0.01). In bronchoalveolar lavage fluid study,
      total cells and neutrophil counts in OVA+LPS mice were elevated but decreased
      after CAM+DXM treatment. In hematoxylin and eosin stain, the CAM+DXM-treated
      group showed less inflammation additively than the monotherapy group. There was
      less total protein, interleukin 17 (IL-17), interferon gamma, and tumor necrosis
      factor alpha in the CAM+DXM group than in the monotherapy group (p<0.001, p<0.05,
      and p<0.001). More histone deacetylase 2 (HDAC2) activity was recovered in the
      DXM and CAM+DXM challenged groups than in the control group (p<0.05). CONCLUSION:
      Decreased IL-17 and recovered relative HDAC2 activity correlated with airway
      resistance and inflammation in a neutrophilic asthma mouse model. This result
      suggests macrolides as a potential corticosteroid-sparing agent in neutrophilic
      asthma.

PMID- 29332326
TI  - Carcinogenic potential of antitumor therapies - is the risk predictable?
AB  - The growing number of successfully cured cancer patients has created a new field
      in oncogenesis. The life expectancy of such patients has increased, however this
      favorable event may create enough time for epigenetic events to occur which can
      cause a new carcinognic event, i.e. a secondary malignancy. The terms in use are
      second primary malignancies as well as therapy-related neoplasms in case the
      treatment of the first neoplasm is a direct cause. Second primary malignancies
      can be hematological neoplasms or solid tumors, with solid tumors having higher
      frequency. Hematological malignancies, especially t MDS (therapy-related
      myelodysplastic syndrome) and t AML (therapy-related acute myeloid leukemia), are
      causally associated with cytotoxic chemotherapy, while secondary solid tumors are
      related to radiotherapy. The pathogenic mechanisms of clonal selection in second
      malignancies are in connection with induction of fusion oncogenes, induction of
      genetic instability, selection of resistant cell clones and hereditary
      predisposition. The most common oncogenic agents are external (antineoplastic
      systemic treatments including radiation therapy), patient-specific factors
      (genetic, demographic, hormonal) and tumorspecific factors (tissue
      radiosensitivity, immunodeficiency). There are special features in the clinical
      picture, biological characteristics and evolution of the second neoplasm -
      different latency period, aggressive course and treatment resistance. Risks,
      types and characteristics of secondary malignancies are analyzed in specific
      groups of patients. For example, the peak of t-AML is several years after a
      primary malignancy and for solid tumors, the risk increases progressively during
      the observation period. In this review, the authors outline that the risk of
      second malignancies is predictable and can be controllable by adequate monitoring
      of patients as well as by personalized treatment of the first neoplasm.

PMID- 29332327
TI  - Stage-II thymoma and emergency coronary artery bypass. To irradiate or not to
      irradiate to avoid radiation induced vascular injury? Case report and literature
      review.
AB  - PURPOSE: The purpose of this study was to present the controversial role of
      adjuvant radiotherapy to a 72-year-old male patient with Masaoka stage II thymoma
      and coronary artery bypass and to review the relevant literature. METHODS: The
      data were collected by relevant studies on PubMed and EMBASE. Articles up to
      March 2017 were included. RESULTS: Although the radiation-induced vascular injury
      to the internal thoracic artery and its suitability for grafting in a patient who
      is candidate for coronary artery bypass is documented, the possible catastrophic
      effect of adjuvant radiotherapy to existing grafts in a patient with prior bypass
      surgery has not been fully investigated. CONCLUSION: The application of
      radiotherapy in a patient with R0 stage II thymoma is currently considered of 2B
      level of evidence but its potential occlusive effect to an underlying coronary
      graft may dramatically affect the survival of the patient and accordingly drop
      the level of evidence of its use.

PMID- 29332328
TI  - Carcinoembryonic antigen and carbohydrate antigen 19-9 serum levels in non-small
      cell lung cancer.
AB  - PURPOSE: Tauo investigate the potential diagnostic and prognostic role of
      carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9) serum
      levels in non-small cell lung cancer (NSCLC). METHODS: One hundred consecutive
      patients with newly diagnosed primary NSCLC were included in this study (88 men
      and 12 women). Blood was drawn before any kind of treatment and the collected
      serum was processed using chemiluminescence in order CEA and CA 19-9 levels to be
      measured. RESULTS: No significant associations between CEA or CA 19-9 levels and
      any tested clinical and pathological parameter were detected. Moreover, CEA
      levels did not seem to affect survival. On the other hand, patients with high CA
      19-9 values (>=37 IU/ml) (median survival: 8 months) had a shorter overall
      survival than patients with low CA 19-9 values (<37 IU/ml) (median survival: 13
      months) (p=0.026). However, CA 19-9 levels did not remain an independent
      prognostic factor in the multivariate survival analysis (p=0.114). CONCLUSION:
      CEA and CA 19-9 serum levels do not seem to have any diagnostic role in NSCLC.
      With regard to their prognostic role, CEA values do not seem to affect the
      prognosis in NSCLC. However, high CA 19-9 values are associated with worse
      prognosis.

PMID- 29332329
TI  - Modified 3-week schedule of gemcitabine plus cisplatin for non-small cell lung
      cancer treatment.
AB  - PURPOSE: Gemcitabine-cisplatin combination is one of the most used schedules for
      non small cell lung cancer (NSCLC). Aiming to enhance dose intensity and reduce
      toxicity, the original 4-week schedule was modified or transformed into a 3-week
      schedule. The purpose of this study was to report the efficacy and tolerability
      of a modified 3-week regimen of gemcitabine-cisplatin. METHODS: Our patients were
      treated with gemcitabine (1000 mg7sol;m2) on days 1, 8 and cisplatin on day 8 (75
      100 mg/m2). The toxicity was recorded according to the NCIC criteria. RESULTS:
      From October 2000 to December 2009 a consecutive series of 196 patients with a
      median age of 62 years and III-IV stage NSCLC received gemcitabine-cisplatin as
      induction therapy (76 patients) or palliative treatment (120 patients). The
      median dose intensity was 89%. In relation to day 8 of chemotherapy, 16.2% of the
      treatments were delayed due to hematologic toxicities. Grade 3-4 anaemia,
      neutropenia and thrombocytopenia was reported in 3.5, 43.8 and 4.6%,
      respectively. Response rate (RR) and median overall survival (OS) were 74% and 11
      months in patients with locally advanced disease, and 46.7% and 9 months in
      metastatic patients, respectively. CONCLUSIONS: In comparison with standard or
      modified schedules of literature, our modified 3-week regimen of gemcitabine-
      cisplatin demonstrated to be equally active, similar for dose intensity and well
      tolerated, with better hematologic toxicity profile in terms of anaemia and
      thrombocytopenia.

PMID- 29332330
TI  - Therapeutic effect of gefitinib in advanced non-small cell lung cancer and its
      effect on the EGFR level in peripheral blood.
AB  - PURPOSE: This study was designed to investigate the therapeutic effect of
      gefitinib in advanced non-small cell lung cancer (NSCLC) and its effect on the
      level of epidermal growth factor receptor (EGFR) in peripheral blood. METHODS: A
      total of 58 patients with NSCLC were treated with gefinitib (iressa) (250 mg per
      day). EGFR levels in the peripheral blood were measured with ELISA assay before
      and after treatment. Statistical analyses of patient quality of life, survival
      and other clinical data were conducted including logistic regression analysis, x2
      test and t-test. Quality of life assessment was quantified based on the Chinese
      version of the QLQ-C30 and QLQ-LC13 questionnaires of the European Organization
      for Research and Treatment of Cancer. RESULTS: The overall response rate to
      iressa was 38% (22 patients), and the disease control rate (response+stable) was
      74% (43 patients). The mean scores of assessment of physiological functions and
      comprehensive quality of life in QLQ-C30 questionnaire were significantly
      increased with an improvement rate of 91-100%. Similarly, the mean scores of
      assessment of disease symptoms in QLQ-LC12 questionnaire were significantly
      reduced with an overall improvement rate of 73-100). Adverse drug effects were
      mainly grade I and II skin rashes and diarrhea. The EGFR levels in peripheral
      blood were significantly decreased after treatment (p<0.05). CONCLUSION: Based on
      our results, gefitinib showed meaningful effects in treating advanced NSCLC,
      significantly improving clinical symptoms and ameliorating the patient quality of
      life.

PMID- 29332331
TI  - EGFR mutations and tumor metastases in patients with nonsmall cell lung cancer in
      the South of Russia.
AB  - PURPOSE: To assess the frequencies of somatic EGFR mutations in the tumor tissues
      of patients with non-small cell lung cancer (NSCLC) residing in the South of
      Russia (SR), and to define the relationship between genetic subtypes of NSCLC and
      the emergence of different types of metastases. METHODS: DNA was extracted from
      formalin-fixed parrafin embedded (FFPE) samples of 721 patients. A total of 29
      somatic EGFR mutations were detected using commercial Therascreen EGFR RGQ PCR
      Kit. RESULTS: EGFR mutations were significantly more frequent in females and non
      smokers even when considering the combination of both factors. The frequency of
      activating EGFR mutations across three age groups (<51, 51-61, >61 years) of
      women with NSCLC was significantly different (x2=10.94, p=0.004) and became
      higher with increasing age. Both activating and resistance mutations of EGFR were
      not associated with the frequency of regional or distant metastases. The
      frequencies of both regional and distant metastases were associated with higher
      disease stage (odds ratio/OR)=16.71; 95% confidence interval (CI): 9.5-29.38;
      p<0.0001, and OR=2.94; 95% CI: 2.22-3.88; p<0.0001, respectively) and
      adenocarcinona histology (OR=6.52; 95% CI: 2.03-20.92; p=0.002, and OR=1.99; 95%
      CI: 0.91-4.34; p=0.083, respectively) even when adjusted for age, gender, and
      smoking status. The risk for regional metastases development was associated with
      poor tumor differentiation (OR=2.91; 95% CI: 1.21-7.02; p=0.017). CONCLUSION:
      EGFR mutations were not associated with the frequency of regional or distant
      metastases in SR patients with NSCLC.

PMID- 29332332
TI  - A study on cellular immune function of patients treated with radical resection of
      pulmonary carcinoma with two different methods of anesthesia and analgesia.
AB  - PURPOSE: To compare the influence on the immune system of two different methods
      of anesthesia and analgesia in patients treated with radical resection of
      pulmonary carcinoma. METHODS: Thirty-four patients treated with radical resection
      of pulmonary carcinoma were randomly divided into two groups (group A and group
      B, 17 cases in each group). Patients in group A were administered total
      intravenous anesthesia (TIVA) without inhaled hypnotics and intravenous analgesia
      while patients in group B were administered TIVA combined with epidural
      anesthesia and epidural analgesia. We compared changes of the T cells subsets
      (CD3+, CD4+, CD8+ and CD4+/CD8+ ratio) and the function of natural killer (NK)
      cells in patients at 4 time points: before anesthesia, immediately after surgery,
      24 hrs after surgery and 72 hrs after surgery. Clinical data were also collected.
      RESULTS: CD8+ in group A and B was significantly increased (p<0.01) while the
      other indexes CD3+, CD4+, CD4+/CD8+ ratio and NK cells) were significantly
      decreased (p<0.05). There was a significant difference in various indexes (except
      NK cell) before anesthesia and 72 hrs after surgery in group A (p<0.01). Various
      indexes of patients in group B at 72 hrs after surgery were restored to the
      values before anesthesia (p>0.05). We observed a significant difference in CD3+,
      CD8+ and CD4+/CD8+ indexes in groups A and B patients at 72 hrs after surgery
      (p<0.05). CONCLUSIONS: TIVA combined with epidural anesthesia and epidural
      analgesia demonstrated less interference with the immune system and determine
      fast recovery in patients with radical resection of pulmonary carcinoma.

PMID- 29332333
TI  - Epigallocatechin gallate from green tea exhibits potent anticancer effects in A
      549 non-small lung cancer cells by inducing apoptosis, cell cycle arrest and
      inhibition of cell migration.
AB  - PURPOSE: Green tea (Camellia sinensis) is considered as a rich source of
      epigallocatechin gallate (EGCG) which has been shown to exert impressive
      pharmacological properties. The anticancer properties of EGCG have been
      extensively studied however, its anticancer activity has not been explored in
      lung cancer. The present study was therefore designed to evaluate the anticancer
      effects of EGCG against non-small cell lung cancer (NSCLC) cell line A-549 and
      normal human fibroblast FR-2 cells. METHODS: Cell viability was assessed by CCK8
      assay, apoptosis by DAPI, annexin V/propidium iodide (PI) and flowcytometery and
      cell cycle analysis by flow cytometry. Cell migration capacity was investigated
      by wound-healing assay and protein expression was examined by Western blotting.
      RESULTS: The results revealed that EGCC could inhibit the proliferation of A-549
      cells in a concentration-dependent manner and exhibited an IC50 of 25 MUM against
      the IC50 of 100 MUM against the normal human fibroblasts. Further evaluation
      revealed that EGCG exerts its anticancer effects via induction of apoptosis,
      modulation of Bax/blc-2 ratio and by triggering G2/M cell cycle arrest.
      Furthermore, EGCG could also inhibit the migration of A5-49 cells in a
      concentration-dependent manner. CONCLUSION: In conclusion, based on our results,
      we believe that EGCG could prove to be an important lead molecule for the
      treatment of lung cancer.

PMID- 29332334
TI  - MiR429 expression level in renal cell cancer and its correlation with the
      prognosis of patients.
AB  - PURPOSE: To test the hypothesis that miR429 expression in renal cancer patients
      is increased and plays a role in the pathogenesis of the disease. METHODS: Twenty
      seven renal cancer patients admitted to our hospital from May 2014 to May 2015
      were enrolled as the study group, and 28 non-cancer patients were selected during
      the same period as the control group. Renal biopsy and serum samples were used to
      detect miR429 expression levels, and the patient histories were obtained to make
      relevant associations to clinical outcomes. In addition, the renal cancer cell
      line SK458 was used for overexpressing or knocking out miR429 in in vitro
      experiments to observe changes in proliferation and apoptosis rates. RESULTS: The
      expression levels of miR429 in renal tissues and serum of renal cancer patients
      were significantly higher compared with control patients (p<0.05). In addition, a
      correlation was found between the levels of miR429 in the serum of renal cell
      cancer patients and their clinical outcome after conventional treatment, with
      patients expressing lower miR429 levels showing better clinical outcomes.
      Finally, experiments with renal cancer cells revealed that the proliferation of
      cells overexpressing miR429 was increased and their apoptosis rate was
      significantly reduced, while the opposite was true in miR429-knockout cells.
      CONCLUSIONS: It seems that miR429 can inhibit normal apoptosis rates and lead to
      high proliferation rates. Accordingly, the higher serum miR429 level in renal
      cancer patients suggests that it plays a role in the pathogenesis of the disease,
      while the differential miR429 levels according to the patients' clinical outcomes
      after treatment suggest that miR429 may be useful as a marker for prognosis.

PMID- 29332335
TI  - Clinicopathological characteristics and survival in Serbian patients with renal
      cell carcinoma: a retrospective analysis.
AB  - PURPOSE: Indications of kidney cancer outcome in lowerincome countries are based
      on an incidence/mortality ratio due to lack of survival information. This study
      was conducted to provide outcome data in Serbian patients with renal cell
      carcinoma (RCC) and to identify prognostic factors that could affect their
      overall survival (OS). METHODS: This retrospective study included 185 patients
      who underwent nephrectomy. We assessed certain clinicopathological data including
      age, gender, tumor size, grade, stage and histological subtypes for their
      possible impact on OS. RESULTS: The 5-year OS was 63.2%. Significant association
      was found between OS and age (log-rank 12.455, p=0.006), tumor size (log-rank
      26.425, p=0.000), grade (log-rank 13.249, p=0.000) and stage (log-rank 43.235,
      p=0.000). Univariate analysis indicated size (p=0.000), grade (p=0.001) and stage
      (p=0.000) as prognostic factors for OS. In multivariate analysis, grade (p=0.014)
      and stage (p=0.000) remained significant predictors of OS. CONCLUSION: Tumor
      grade and stage were identified as independent prognostic factors of OS survival
      in Serbian patients with RCC.

PMID- 29332336
TI  - Downregulation of guanine nucleotide-binding protein beta 1 (GNB1) is associated
      with worsened prognosis of clearcell renal cell carcinoma and is related to VEGF
      signaling pathway.
AB  - PURPOSE: Clear-cell renal cell carcinoma (ccRCC) is characterized by genetic
      abnormalities, while the role of Guanine Nucleotide-Binding Protein Beta 1 (GNB1)
      in ccRCC has not been studied. We thus aimed to evaluate the expression and
      prognostic value of GNB1 in ccRCC. METHODS: A two-stage study (exploration and
      validation) was conducted using in silico and immunohistochemical (IHC) scoring
      of ccRCC samples from our institute, to evaluate the association between GNB1
      expression and clinicopathological parameters of ccRCC patients. Pathway analyses
      were performed for genes coexpressed with GNB1 using the KOBAS platform to
      profile the function of GNB1 and IHC validation. RESULTS: In the exploration
      stage, data from TCGA ccRCC dataset were reproduced, which contained 537 patients
      with ccRCC and found that downregulation of GNB1 was significantly associated
      with worse prognosis. IHC staining from the Human Protein Atlas showed
      significantly downregulation of GNB1 in ccRCC tissue compared with normal kidney.
      Pathway analysis showed significantly altered vascular endothelial growth factor
      (VEGF) signaling pathways among which expressions of 3 genes (WASF2, NRP1, and
      HIP1) were significantly associated with GNB1 expression, respectively. In the
      validation stage, included were 80 ccRCC samples and GNB1 expression was scored
      using IHC positivity. GNB1 expression was negatively associated with tumor stage,
      lymph node invasion, metastasis, older age, and increased tumor grade. Female
      gender and receiving neoadjuvant therapy were also associated with decreased GNB1
      expression. The expressions of WASF2, NRP1 and HIP1 were also studied and found
      that they were significantly associated with GNB1. CONCLUSION: GNB1 was
      downregulated in ccRCC. Decreased GNB1 expression was associated with worsened
      disease characteristics and prognosis. GNB1 was related with VEGF signaling in
      ccRCC, implying a therapeutic potential of this factor.

PMID- 29332337
TI  - Systemic treatment and primary tumor location in patients with metastatic
      colorectal cancer.
AB  - PURPOSE: Tumor location (right-sided vs. left-sided) is known to exert a
      significant influence on the prognosis of primary colorectal cancer (CRC). Given
      the genetic continuity between primary and metastatic lesions, we aimed to
      summarize the existing literature on the prognostic implications of primary tumor
      site as well as to examine the response to chemotherapy by primary tumor location
      in patients with metastatic CRC (mCRC). METHODS: A structured review of the
      literature was performed between 6/1/2016-7/1/2016 using the Pubmed database.
      Original research articles published between 1/1/2000- 07/01/2016 were considered
      eligible. The primary endpoints were overall survival (OS)/ progression free
      survival (PFS) and response to systemic treatment in patients with mCRC. RESULTS:
      Eleven studies were included. Tumor site was a strong independent predictor of
      worse OS/PFS in 9 studies, with right-sided tumors having worse prognosis in all
      cases. Furthermore, 6 studies demonstrated an inferior response to systemic
      treatment or worse prognosis following the administration of specific regimens
      among patients with right-sided cancers. As such, there is significant evidence
      that right-sided lesions are associated with poor outcomes and resistance to
      systemic treatment. CONCLUSION: Consequently, primary tumor location should be a
      consideration, when the administration of systemic therapy is contemplated in
      mCRC.

PMID- 29332338
TI  - X-ray-induced epithelial-mesenchymal transition in SW480 colorectal cancer cells
      and its potential mechanisms.
AB  - PURPOSE: The purpose of this study was to investigate the relation between X-ray
      irradiation and epithelial-mesenchymal transition (EMT), as well as the potential
      mechanisms of X-ray-induced EMT in SW480 colorectal cancer (CRC) cells. METHODS:
      It is well known that EMT plays a critical role in invasive and metastatic of
      colorectal cancer progression. However, the possible role of X-ray irradiation on
      EMT in colorectal cancer is widely disputed and its potential mechanisms are
      unclear. SW480 CRC were irradiated (0, 2, 4, 6, 8 Gy) and cultured for 48 hrs,
      and then the cellular morphology was observed. Protein and mRNA expressions were
      examined by Western blot and QRT-PCR. Cell migratory and invasive capacity was
      evaluated by Transwell assay. RESULTS: In the 2, 4, 6, 8 Gy groups, SW480 CRC
      exhibited a classical mesenchymal phenotype compared with the 0 Gy group. The
      expression of E-cadherin was significantly decreased, while the expression of
      vimentin and Smad3 was significantly increased in the 2, 4, 6, 8 Gy groups
      (p<0.05) compared with the 0 Gy group; still, the expression of K-ras decreased
      in the 4, 6, 8 Gy groups (p<0.05) compared with the 0 and 2 Gy groups.
      Furthermore, the cell migration and invasion capacity was significantly enhanced
      in the 4 and 8 Gy groups compared with the 0 Gy group (p<0.05). CONCLUSION: These
      results support the fact that X-ray irradiation can induce EMT through promoting
      Vimentin and Smad3 expression in SW480 CRC cells.

PMID- 29332339
TI  - p21 does, but p53 does not predict pathological response to preoperative
      chemoradiotherapy in locally advanced rectal cancer.
AB  - PURPOSE: Preoperative chemoradiotherapy (CRT) is the standard treatment option in
      locally advanced rectal cancer. The tumor response is assessed through tumor and
      nodal downstaging and the tumor regression grade. Currently, there is no method
      to predict a tumor response to CRT. We aimed to evaluate whether p21 and p53
      expressions could be a reliable predictors of pathological response to CRT.
      METHODS: Fifty patients with locally advanced rectal cancer were treated with
      preoperative radiotherapy combined with mitomycin C and capecitabine. p21 and p53
      immumohistochemical staining was performed on pretreatment biopsies and the
      results were compared with tumor regression according to grading systems by
      Dworak (TRG grades) and by Wheeler (RCRG grades). RESULTS: Testing RCRG grades in
      relation to p21 expression showed statistically significant difference (p=0.021).
      RCRG 3 (poor response) was more frequent in the group of patients with low p21.
      According to Dworak, grade 4 (complete regression) was more frequent in the group
      of patients with positive p21 expression (p=0.032). Significant difference in p21
      expression in grade 4 group compared with all other grade groups was also found
      (p=0.007). Patients with immune expression of p21 had significantly higher
      percentage of complete regression in comparison to the patients with low
      expression of p21. We haven't found any correlation between p53 expression and
      histopathological (HP) as well as regression grades. CONCLUSION: According to
      both grading systems, our results suggest that p53 expression does not, but p21
      expression does predict pathological response to preoperative CRT.

PMID- 29332340
TI  - Imperatorin shows selective antitumor effects in SGC-7901 human gastric
      adenocarcinoma cells by inducing apoptosis, cell cycle arrest and targeting
      PI3K/Akt/m-TOR signalling pathway.
AB  - PURPOSE: The main purpose of the present study was to determine the anticancer
      properties of imperatorin - a naturally occurring coumarin compound - against SGC
      7901 human gastric adenocarcinoma cells and the mouse fibroblast cell line 3T3
      (normal cell line). METHODS: Imperatorin effects on apoptosis induction, cell
      cycle phase distribution and PI3K/Akt/m-TOR signalling pathways were studied. MTT
      cell viability assay examined the compound's cytotoxic potential, while inverted
      phase contrast microscopy and fluorescence microscopy techniques were used to
      study morphological changes induced in SGC-7901 cells by imperatorin. Flow
      cytometry examined its effects on cell cycle progression while Western blot assay
      was used to study changes in protein expressions of PI3K/Akt/m-TOR pathway.
      RESULTS: Imperatorin induced a dose-dependent growth inhibition of the SGC-7901
      gastric cancer cells with an IC50 value 62.6 MUM, while in case of normal 3T3
      mouse fibroblast cells, the drug did not show significant toxicity (IC50 value
      195.8 MUM), indicating that the drug selectively induced cytotoxicity in gastric
      cancer cells. The cells became rounded up, shrunken in size and got detached from
      the monolayer attached to well surface. Cells treated with 10, 75 and 175 MUM
      imperatorin indicated that they began to emit yellow or red fluorescence which is
      an indication of early or late apoptosis respectively. Imperatorin also induced
      significant DNA fragmentation along with increasing the fraction of sub-G1 cells,
      indicating a sub-G1 cell cycle arrest. CONCLUSION: Imperatorin could prove an
      important lead molecule for the treatment of gastric cancer and deserves further
      research in vivo against more cell lines.

PMID- 29332341
TI  - Association of the combined parameters including the frequency of primary cilia,
      CD8+ tumor infiltrating lymphocytes and PD-1 expression with the outcome in
      intestinal cancer.
AB  - PURPOSE: Primary cilium (PC) is considered to be a functional homologue of the
      immune synapse. Microtubule structures, PC of cancer associated fibroblasts and
      immune synapses between cytotoxic CD8+ tumor infiltrating lymphocytes (TILs) and
      cancer cells, are regularly found in varying amounts in the microenvironment of
      solid tumors. The purpose of this study was to find out the potential association
      and combined prognostic significance of the frequency of PC, PD-1 and CD8+ TILs
      in patients with intestinal cancer. METHODS: The frequency of PC, programmed cell
      death protein-1 receptor (PD-1) expression and the frequency of stromal and
      intraepithelial CD8+TILs were evaluated in samples of colorectal adenocarcinoma
      (32 patiens) and small bowel cancer (8 patients). RESULTS: The median frequency
      of PC was 0.25%. The expression of PD1 was <5% in 34 patients, 5-25% in 5
      patients and 26-50% in 1 patient. The frequency of stromal CD8+ TILs was negative
      in 3 patients, <25% in 26, 26-50% in 10 and >50% in 1 patient, respectively.
      Intraepithelial CD8+ TILs were not detectable in 14, <25% in 24 and 26-50% in 2
      patients, respectively. Statistically, the frequency of PC and PD-1 positivity
      were significantly associated (p=0.004). An association between the PC frequency
      and intraepithelial CD8+ TILs was of borderline statistical significance
      (p=0.059). An index combining the frequency of PC and stromal CD8+ TILs, but not
      the combination of frequency of PC and intraepithelial CD8+ TILs, was of
      borderline prognostic significance (p=0.067). CONCLUSIONS: The present study
      provides the first data on the potential association and combined prognostic
      significance of frequency of PC, PD-1 and CD8+ TILs in patients with intestinal
      cancer.

PMID- 29332342
TI  - Study on the association between PI3K/AKT/mTOR signaling pathway gene
      polymorphism and susceptibility to gastric cancer.
AB  - PURPOSE: Excessive activation of PI3K/AKT/mTOR signaling pathway is one of the
      most common changes in human cancers, and single nucleotide polymorphisms (SNPs)
      existing in its functional region can affect the occurrence process of a variety
      of cancers. This study aimed to screen out the SNPs associated with
      susceptibility to gastric cancer in the PI3K/AKT/mT0R signaling pathway. METHODS:
      In this case-control study, the tagging SNPs in the promoter region5'-UTR, exon
      region or 3'-UTR of PIK3CA, PIK3CB, PIK3R1, PIK3R2, PIK3R3, AKT1, AKT2, AKT3 and
      mTOR genes were screened out. The relationship between the genetic variation of
      PI3K/AKT/mT0R signaling pathway genes and the susceptibility to gastric cancer in
      Chinese Han population was investigated by this casecontrol study. RESULTS: The
      results showed that the polymorphisms of the two loci, PIK3R3 rs7536272 (Additive
      model: OR=1.16, 95% CI=1.01-1.35) and mTOR rs2295080 (GG vs TT: OR=0.75, 95%
      CI=0.60-0.94; Additive model: OR=0.78, 95% CI=0.66- 0.93), were associated with
      the risk of gastric cancer in the studied population and there was a combined
      effect between the two loci (ptrend=0.005). CONCLUSIONS: In conclusion, the
      polymorphisms of the two loci, PIK3R3 rs7536272 and mTOR rs2295080, on the
      PI3K/AKT/mTOR signaling pathway genes are associated with genetic susceptibility
      to gastric cancer in Chinese population.

PMID- 29332343
TI  - Clinical relevance of telomerase polymorphism for breast cancer: A systematic
      review.
AB  - PURPOSE: To perform a systematic review to explore the clinical relevance of
      hTERT polymorphisms for breast cancer (BC). METHODS: Twenty-nine polymorphic
      regions were evaluated after comprehensive searching of 1236 articles, and
      selection of 9 publications (total of 12986 cases and 16758 controls). RESULTS:
      About the influence of hTERT variants in BC risk, 3 studies showed that the
      variant rs2736098 was associated with increasing risk. The variants rs10069690
      and rs2853676 were also described as risk factors for BC. Only one variant
      rs2736100 presented as risk factor for BC. MNS16A genotype influenced the risk of
      BC in an Iranian, but not in the Greek and American populations. The associations
      of 5 hTERT variants with expression of hormone receptors were also evaluated in
      some studies. One study showed that the variant rs10069690 was associated to the
      estrogen receptor (ER)-negative and triple negative subtype, but other authors
      did not find the same results. In addition, the association of rs273618 with ER
      /progesterone receptor (PR)+ cases, and rs10069690, rs2735940, rs4246742 and
      rs2736100 with both negative receptors were described. After data reanalyses, we
      found that the variant rs2735940 and rs2736100 were associated with ER-/PR- cases
      among patients with BC. Also, the variant rs2736100 was associated with ER+/PR+
      cases and the variant rs2736118 was associated to ER+/PR+ and ER-/PR+ cases.
      CONCLUSIONS: The associations between hTERT variants and BC risk and outcomes
      could be useful since a polymorphism can be identified before the diagnosis, but
      the heterogeneity of data and analyses found in different studies lead to many
      controversies.

PMID- 29332344
TI  - In vitro antitumor activity of guttiferone-A in human breast cancer cells is
      mediated via apoptosis, mitochondrial mediated oxidative stress and reactive
      oxygen species production.
AB  - PURPOSE: Breast cancer is the second most frequently diagnosed cancer and is
      considered as the main cause of cancer related death in females. It is estimated
      that about one-third of women with breast cancer develop metastases and
      eventually die of this disease. The main treatment options for breast cancer
      include surgical interventions followed by chemotherapy, hormonotherapy or
      radiation. However, the side effects associated with the treatment of breast
      cancer negatively affects the quality of patient's life. In the present study a
      plant-derived compound, guttiferone- A, was evaluated for its anticancer activity
      against MCF-7 breast cancer cell line. METHODS: MTT assay was used to evaluate
      the cytotoxic effects while phase contrast microscopy was used to assess the
      effects of the compound on cell morphology. Effects on reactive oxygen species
      (ROS) and mitochondrial membrane potential were evaluated by flow cytometric
      analysis. RESULTS: It was observed that guttiferone-A reduced the cell viability
      of MCF-7 cancer cells in a dose-dependent manner. The IC50 for guttiferone-A was
      found to be 15 MUM against MCF-7 cells. Moreover, guttiferone-A induced the
      production of high levels of ROS and caused significant reduction in the
      mitochondrial membrane potential. Additionally, guttiferone-A also induced
      apoptosis in MCF-7 cancer cells in a dose-dependent manner. CONCLUSION: Taken
      together, we conclude that guttiferone- A is a potential anticancer molecule and
      may prove to be a lead molecule in cancer drug discovery.

PMID- 29332345
TI  - Correlation between miR-19a inhibition and radiosensitivity in SiHa cervical
      cancer cells.
AB  - PURPOSE: MicroRNAs (miRs) have been implicated in many aspects of tumor cell
      development and survival, including sensitivity to radiotherapy. In particular,
      miR-19a regulates the proliferation of cervical cancer cells, but its role in
      radiosensitivity is not known. Here, we describe the consequence of silencing miR
      19a using antisense oligonucleotides (ASO) on the radiosensitivity of human
      cervical cancer SiHa cells. METHODS: Following transfection with miR-19a-ASO or
      control-ASO, SiHa cells were exposed to X-rays to determine their proliferation.
      RESULTS: Silencing of miR-19a significantly improved the sensitivity of SiHa
      cells to radiotherapy by reducing proliferation, increasing apoptosis,
      upregulating BAX, and downregulating Bcl-2. CONCLUSION: Overall, inhibiting miR
      19a significantly improves the sensitivity of SiHa cells to radiotherapy, which
      could lead to new methods for the treatment of cervical cancer.

PMID- 29332346
TI  - Vaginal packing volume impact on dose parameters during radiography and computed
      tomography based postoperative brachytherapy of cervical carcinoma.
AB  - PURPOSE: To investigate the influence of the vaginal packing volume on the
      registered dose parameters evaluated by radiography (2D) and computed tomography
      (CT) (3D) based brachytherapy planning in cervical cancer patients treated with
      postoperative radiotherapy. METHODS: The postoperative radiotherapy was performed
      in 40 cervical cancer patients with increased risk for disease relapse. Both,
      radiography and CT based brachytherapy planning were done in all patients.
      Vaginal packing volume was evaluated by clinical target volume (CTV)uk, assessed
      on CT scans and analyzed according to the registered dose parameters: doses
      delivered to the organs at risk (OAR) and the defined CTV, using both planning
      methods. RESULTS: CTVuk volume had statistically significant influence on CTV
      coverage with the prescribed brachytherapy doses D90 (p<0.01) and D100 (p<0.01),
      revealing a CTVuk cut-off value of 25.6 cm3. Dividing the patients into two
      groups according to the cutoff value, we found a statistical significance in the
      registered doses to the rectal wall and no significance in the bladder wall doses
      between the groups. Also, a statistically significant, negative correlation was
      found between CTVuk and following doses: Rmax (rho= -0.34, p<0.05), D0.1cc (rho= 
      0.76, p<0.01), D1cc (rho= -0.74, p<0.01) and D2cc (rho= -0.72, p<0.01), D90 (rho=
      -0.80, p<0.01), D100 (rho= -0.7, p<0.01). CONCLUSION: If the brachytherapy
      vaginal packing is of a large volume (more than 25.6 cm3), an asymmetric
      deformation of the proximal part of the vaginal cavity might appear, leading to
      inappropriate dose coverage of the CTV part of the vaginal mucosa. Also, making a
      vaginal packing volume larger than 25.6 cm3 made no further reduction in the
      bladder dose, but it made a statistically significant further reduction in the
      rectal doses.

PMID- 29332347
TI  - Genetically engineered bone marrow-derived mesenchymal stem cells co-expressing
      IFN-gamma and IL-10 inhibit hepatocellular carcinoma by modulating MAPK pathway.
AB  - PURPOSE: One of the major challenges in delivering cytokines for the treatment of
      hepatocellular carcinoma (HCC) is the mode of delivery. This study hypothesized
      that genetically engineered bone marrow derived mesenchymal stem cells (BMSCs) co
      expressing IFN-gamma and IL-10 can serve as a potential therapeutic strategy in
      the treatment of HCC by inhibiting cell proliferation. METHODS: Male Sprague
      Dawley rats (n=5, 200-250 g) for BMSCs isolation and Nude/SCID mice (n=35,12-20g)
      to develop liver cancer xenograft model were used. Mice were subcutaneously
      injected HepG2 cell suspension on left flank. BMSCs were genetically engineered
      with the recombinant lentiviral vectors expressing IFN-gamma and IL-10. The
      experiments were performed in 5 groups (phosphate buffered saline/PBS, BMSCs,
      BMSC-IFN-gamma, BMSC-IL-10 and BMSC-IFN-gamma-IL-10) and the genetically
      engineered BMSCs were transplanted into HCC mice. Cell viability was measured by
      MTT assay followed by the evaluation of the effect of cell-cycle regulators (p21,
      p27, cyclin D1 and Rb). Protein expression of p38, ERK and JNK was assessed by
      immunohistochemistry using the cell proliferation marker Ki67. RESULTS: The
      combination of two cytokines (IFN-gamma and IL- 10) engineered into BMSCs
      resulted in a significant reduction in HepG2 cell viability (*p<0.05 vs PBS
      treated and #p<0.05 vs BMSC-treated group). Significantly increased expression of
      cell cycle inhibitors p21 and p27 in parallel with reduced cyclin D1 expression
      were observed. Reduced phosphorylation of Rb demonstrated the repression of G1/S
      progression. BMSC-IFN-gamma-IL-10 treatment significantly reduced the tumor
      growth at the end of 36 days compared to the group treated with PBS or BMSCs
      alone. This effect was accompanied with the modulation of MAPK pathway with the
      activation of p38 and JNK, and inactivation of ERK. CONCLUSION: The co-expression
      of IFN-gamma and IL-10 in BMSCs inhibits HCC in vitro and in vivo by modulating
      cell cycle regulators and MAPK pathway.

PMID- 29332348
TI  - Sorafenib combined with radiofrequency ablation as treatment for patients with
      hepatocellular carcinoma: a systematic review and meta-analysis.
AB  - PURPOSE: To evaluate the safety and efficacy of a combination of sorafenib and
      radiofrequency ablation (RFA) in patients with hepatocellular carcinoma (HCC).
      METHODS: A systematic literature search was conducted using PubMed, Embase, the
      Cochrane Library, China National Knowledge Infrastructure (CNKI), China Biology
      Medicine disc (CBMdisc), WanFang Database, for all years up to January 2017.
      Pooled analyses of overall survival (OS), tumor- free survival, recurrence rates
      and adverse events were performed. RESULTS: IA total of 7 case control studies
      consisting of 1765 HCC patients were selected and included in this metaanalysis.
      Patients treated with sorafenib-RFA and sorafenib alone, RFA alone and surgery
      had no significant differences in 1-year OS (p=0.310), 2-year OS (p=0.262), 3
      year OS (p=0.179), 4-year OS (p=0.238) and 5-year OS (p=0.933); 1-year recurrence
      rate (p=0.653), 2-year recurrence rate (p=0.416), 3-year recurrence rate
      (p=0.304), and 5-year recurrence rate (p=0.807); 1-year tumor-free survival rate
      (p=0.943), 3-year tumor-free survival rate (p=0.825), 5-year tumor-free survival
      rate (p=0.893) and overall adverse events (p=0.097). CONCLUSION: RFA-sorafenib
      combination may not be a better approach for patients with HCC. More well
      designed randomized clinical trials (RCTs) should be performed before we finally
      arrive at a rational comprehension about the therapeutic value of the discussed
      options.

PMID- 29332349
TI  - Characteristics and clinical significance of recurrent laryngeal nerve lymph node
      metastasis in esophageal squamous cell carcinoma.
AB  - PURPOSE: The recurrent laryngeal nerve lymph nodes (RLN LNs) are among the most
      common metastatic sites in esophageal cancer, and the dissection of these lymph
      nodes (LNs) is considered beneficial. The purpose of this study was to evaluate
      the characteristics of RLN LN metastases from esophageal squamous cell carcinoma,
      and the effects of these metastases on the prognosis of patients. In addition, we
      aimed to determine the reasonable range of dissection of regional LNs. METHODS:
      The clinical data from 348 patients who underwent resection for esophageal
      carcinoma were retrospectively analyzed. RESULTS: Recurrent laryngeal nerve palsy
      occurred in 37.6% of the patients. In a subgroup of patients with lower
      esophageal tumors, cervical LN metastases were significantly more common in
      patients with positive rather than negative RLN LNs. The primary tumor site,
      tumor differentiation, and tumor invasion depth were factors that significantly
      influenced RLN LN metastasis. Multivariate analysis revealed that RLN LN
      metastasis was a significant factor associated with overall survival (OS) and
      disease-free survival (DFS) (p<0.001). CONCLUSION: Metastasis to RLN LNs is a
      reliable indicator of cervical LN metastasis in middle/lower thoracic esophageal
      cancer. RLN LN metastasis may act as a prognostic indicator for patients with
      esophageal squamous cell carcinoma.

PMID- 29332350
TI  - Short- and long-term outcomes of minimally invasive esophagectomy in elderly
      patients with esophageal squamous cell carcinoma.
AB  - PURPOSE: In recent years, there has been an increase in the number of elderly
      patients undergoing surgery for esophageal squamous cell carcinoma (ESCC).
      However, there are few studies on short- and long-term outcomes of minimally
      invasive esophagectomy (MIE) in such patients. The purpose of this study was to
      report both short- and long-term outcomes of MIE in elderly patients with ESCC.
      METHODS: A total of 273 patients with ESCC underwent MIE at our hospital from
      January 2010 to December 2016. Patients were divided into elderly (>=70 years)
      and nonelderly (<70 years) groups based on age at the time of surgery. Groups
      were compared with regard to general preoperative data, intraoperative data,
      postoperative 30-day complications and their severity, pathological result,
      recurrence, overall survival (OS), and disease-free survival (DFS) rates.
      RESULTS: The elderly group was characterized by higher Charlson Comorbidity Index
      >2 and American Society of Anesthesiologists (ASA) grade. Comparisons of other
      general preoperative data showed no significant differences. In addition, there
      were no significant differences in short-term outcomes except for postoperative
      30-day complication rate. Although 30-day postoperative complication rate was
      higher in the elderly group compared with the nonelderly group, the incidence of
      major complications was similar between groups. Cancer recurrence, 5-year OS, and
      5-year DFS rates also were similar between groups. CONCLUSION: Although elderly
      patients with ESCC had higher Charlson Comorbidity Index and ASA grade, they
      could achieve short- and long-term outcomes of MIE similar to those of nonelderly
      patients.

PMID- 29332351
TI  - Cytoreductive surgery and hyperthermic intraperitenoal chemotherapy (HIPEC) for
      colorectal and appendiceal carcinomas with peritoneal carcinomatosis.
AB  - PURPOSE: Cytoreductive surgery combined with intraperitoneal chemotherapy has
      been established as the standard treatment for selected patients with peritoneal
      malignancy. The purpose of the study was the presentation of the 10- year
      experience with cytoreductive surgery and intraperitoneal chemotherapy in
      patients with peritoneal carcinomatosis of colorectal and appendiceal origin.
      METHODS: Clinical and histopathological variables were retrospectively reviewed
      in a prospectively maintained database. All patients underwent cytoreductive
      surgery with the purpose of complete or near-complete cytoreduction. The
      variables were correlated to survival, and recurrences. Morbidity and hospital
      mortality were recorded. RESULTS: From 2006-2016 100 patients underwent
      cytoreductive surgery for colorectal and appendiceal carcinomas with peritoneal
      carcinomatosis. The hospital mortality and morbidity were 2% and 43%
      respectively. Completeness of cytoreduction (CC) 0 surgery was possible in 51% of
      the patients. The median and 10-year survival were 13 months and 23%
      respectively. The completeness of cytoreduction, performance status and the lymph
      node status were identified as prognostic indicators of survival. The recurrence
      rate was 55%. The completeness of cytoreduction, the lymph node status, and the
      use of postoperative adjuvant systemic chemotherapy were identified as prognostic
      variables of recurrence. CONCLUSION: Nearly half of the patients with peritoneal
      carcinomatosis of colorectal and appendiceal origin may undergo complete
      cytoreduction and nearly half of them may enjoy long-term survival.

PMID- 29332352
TI  - Puerarin leads to K562 cell apoptosis of chronic myelogenous leukemia via
      induction of autophagy.
AB  - PURPOSE: To study the effects of puerarin on the viability, apoptosis and
      autophagy of K562 cells of chronic myelogenous leukemia (CML), and to provide a
      basis for the study on antitumor mechanism of puerarin. METHODS: K562 cells of
      human CML were taken as the study material and puerarin was applied in different
      concentrations. The effect of puerarin on cell viability was detected via
      cholecystokinin-8 (CCK8) and lactate dehydrogenase (LDH). Flow cytometry and
      western blot (WB) were used to detect cell apoptosis, while Cyto-ID and WB were
      used to detect the cell autophagy level. RESULTS: Puerarin inhibited the K562
      cell viability and increased cell apoptosis and autophagy in a dose-dependent
      manner. After 3-methyladenine (3-MA) autophagy inhibitor was used, puerarin's
      induction of cell autophagy was inhibited, and its apoptosis induction was also
      inhibited. CONCLUSIONS: Puerarin increases the cell apoptosis through induction
      of autophagic apoptosis of K562 cells.

PMID- 29332353
TI  - Aesculetin (6,7-dihydroxycoumarin) exhibits potent and selective antitumor
      activity in human acute myeloid leukemia cells (THP-1) via induction of
      mitochondrial mediated apoptosis and cancer cell migration inhibition.
AB  - PURPOSE: The main target of the present research was to examine the antitumor
      properties of aesculetin in human acute myeloid leukemia cancer cells (THP-1) and
      peripheral blood mono-nucleated cells (PBMCs) (used as normal cell line model)
      along with the determination of its effects on induction of apoptosis, inhibition
      of cancer cell migration and changes in Bcl-2/Bax protein expressions. METHODS:
      MTT colorimetric bioassay was performed to study the impact of this natural
      compound on cytotoxicity of both cell types. Moreover, transmission electron
      microscopy (TEM), inverted phase contrast and fluorescence microscopic techniques
      were used to study the effects on cell morphology and cellular ultrastructural
      details connected with apoptosis. The effects of aesculetin on Bcl-2/Bax protein
      expressions were assessed by Western blot method. RESULTS: Selective and dose
      dependent antiproliferative activity of aesculetin in human acute myeloid
      leukemia cancer cells was observed. However, the compound did not induce
      significant cell growth inhibition of PBMCs, which were used as normal cell
      controls. Fluorescence and inverted phase contrast microscopic techniques
      revealed that aesculetin led to morphological changes suggestive of apoptosis
      (cell shrinkage, chromatin abridgment and membrane blebbing). TEM analysis showed
      that aesculetin led to fragmented plasma membrane along with appearance of
      spherical projections (apoptotic bodies). The wound scratch widened after
      aesculetin treatment, indicating that aesculetin exhibits anticancer effects by
      suppressing the cancer cell migration. Aesculetin led to significant and dose
      dependent reduction in the Bcl-2 expression while the expression of Bax was
      significantly enhanced resulting in overall reduction of Bcl-2/Bax ratio.
      CONCLUSION: The results of the present work revealed that aesculetin exhibits
      selective anticancer effects in THP-1 human leukemia cells without causing much
      cytotoxicity in PBMCs. It also led to significant apoptosis induction, inhibition
      of cancer cell migration and decrease in Blc-2/Bax ratio.

PMID- 29332354
TI  - Inhibition of telomerase potentiates enzalutamide efficiency of androgen
      sensitive human prostate cancer cells.
AB  - PURPOSE: Androgen deprivation therapy (ADT) is one of the main strategies to
      treat prostate cancer (PCa) at various stages of its development. Androgen
      receptor (AR) antagonists such as enzalutamide are mainstay treatments for
      castration-sensitive prostate cancer. Though, a majority of patients initially
      respond to ADT, most will eventually progress to castrate-resistant, due to the
      development of different mutations on the AR. PCa cells express high telomerase
      activity, and there is a correlation between the total activity of telomerase and
      the Gleason score. Therefore, we hypothesized that the combination of
      enzalutamide plus a telomerase inhibitor could be more effective than
      enzalutamide alone in decreasing cell survival. METHODS: In this study MTT test,
      RT-qPCR and imagebased cytometry were used to investigate cell viability,
      apoptosis and cell cycle progression of androgen-responsive human prostate cancer
      LNCaP cells. The cells were treated with 5 MUM enzalutamide and 40 MUM telomerase
      inhibitor BIBR 1532, or with their combinations for 72 hrs. RESULTS: Enzalutamide
      and BIBR 1532 alone inhibited cell proliferation in a dose-dependent manner. The
      combinations of the two agents could synergistically induce apoptotic and
      necrotic cell death. Either inhibition of telomerase by BIBR 1532 or AR blockages
      by enzalutamide decreased prostate-specific antigen (PSA) and the catalytic
      component of telomerase, hTERT, expression. CONCLUSION: These results suggest
      that telomerase inhibition therapy may contribute to the efficacy of enzalutamide
      in the androgen-sensitive PCa model.

PMID- 29332355
TI  - Antitumor activity of 4-O-Methylhonokiol in human oral cancer cells is mediated
      via ROS generation, disruption of mitochondrial potential, cell cycle arrest and
      modulation of Bcl-2/Bax proteins.
AB  - PURPOSE: The plant-derived natural product 4-O-methylhonokiol (MH) has been
      reported to possess tremendous pharmacological potential ranging from
      neuroprotection to anticancer activity. However, the anticancer activity of MH in
      oral squamous cell carcinoma (OSCC) cells has not been evaluated. In the present
      study, MH was evaluated for its anticancer activity against OSSC PE/CA-PJ41 cells
      and the possible underlying mechanism was determined. METHODS: Cell cytotoxicity
      was evaluated by colorimetrybased MTT assay while the effects on cell cycle phase
      distribution were assessed by flow cytometry. Effects of MH on reactive oxygen
      species (ROS) production and mitochondrial membrane potential (MMP) were
      evaluated by flow cytometry. Western blot assay was finally utilized to study the
      effects of MH on key cancer and apoptosis-linked proteins including Bax and Bcl
      2. RESULTS: MH induced cytotoxicity in OSCC PE/CA-PJ41 cells with an observed
      IC50 of 1.25 MUM. It also caused significant increase in the production of ROS
      and disrupted the MMP in a dose-dependent manner. The reduction in MMP favored
      mitochondrial apoptotic pathway which was further confirmed by determining the
      expression of Bax and Bcl-2. It was observed that MH downregulated the expression
      of Bax and upregulated the expression of MMP, ultimately leading to apoptosis of
      OSSC PE/CA-PJ41 cells. Additionally, MH also caused G2/M cell cycle arrest in a
      dose-dependent manner. CONCLUSION: Taken together, our results indicate that 4
      Omethylhonokiol may prove a potential natural anticancer molecule against human
      oral carcinoma cells.

PMID- 29332356
TI  - beta-Aescin shows potent antiproliferative activity in osteosarcoma cells by
      inducing autophagy, ROS generation and mitochondrial membrane potential loss.
AB  - PURPOSE: Osteosarcoma is one of the frequent bone tumor affecting mainly children
      and is associated with considerable mortality. The limited availability of
      anticancer drugs and less efficacious treatment options have led to poor survival
      rates of patients with osteosarcoma. Therefore, there is need to look for more
      viable treatment options and against this backdrop, natural products may prove
      handy. Therefore the aim of the present study was to evaluate the anticancer
      activity of a natural product of plant origin, beta-aescin, against U2OS human
      osteosarcoma cells. METHODS: U205 human osteosarcoma cell line was used in this
      study. Antiproliferative activity was determined by MTT assay. Reactive oxygen
      species (ROS) and mitochondrial membrane potential (MMP) were evaluated by flow
      cytometry. Autophagy was detected by monodansylcadaverine (MDC) staining and
      immunofluorescence. Protein expression was examined by western blotting. RESULTS:
      The results indicated that beta-aescin showed significant anticancer activity
      against U2OS human osteosarcoma cells and exhibited an IC50 of 40 MUM. beta
      aescin treatment caused significant increase in ROS and decrease in the MMP. The
      anticancer effect of beta-aescin was found to be due mainly to autophagic cell
      death as evidenced from MDC staining and immunofluorescence. Moreover, beta
      aescin caused significant increase in the expression levels of LC3- II protein in
      U2OS osteosarcoma cells in a time and dosedependent manner. CONCLUSION: Taken
      together we propose that beta-aescin may prove a lead molecule in the management
      of osteosarcoma and deserves further research efforts.

PMID- 29332357
TI  - Management of B3 lesions of the breast: implementations of current
      recommendations in clinical practice.
AB  - PURPOSE: Stereotactic needle breast biopsy and vacuum assisted breast biopsy have
      replaced wide local excision in the last decades. B3 lesions of the breast
      represent a particular subgroup which is difficult to manage. The purpose of the
      present study was to present our experience with this specific type of lesions
      and to examine the conformity of Princess Margaret Hospital with current
      recommendations. METHODS: We retrospectively searched for patients that attended
      the Breast Clinic of Princess Alexandra Hospital during the period 2012-2015, and
      were diagnosed with B3 lesions during stereotactic needle core biopsy. RESULTS:
      In total 24 patients with B3 lesions were identified. Among them 6 women had
      synchronous malignant lesions and were excluded from our study. From the
      remaining, 8 patients presented with a single B3 lesion and 10 with multiple B3
      lesions. Twelve of our patients underwent stereotactic vacuum-assisted biopsy
      (VAB). Ten patients underwent only core biopsy, 8 underwent only VAB biopsy and 3
      lesions were investigated with both core biopsy and VAB. CONCLUSIONS: The
      findings of our study support the applicability of the current recommendations
      for the surgical management of B3 breast lesions. Core needle biopsies and VAB
      are equally efficacious with wide local excision for the differential diagnosis
      of lesions of uncertain malignant potential, thus limiting the necessity of open
      surgery.

PMID- 29332358
TI  - A study on basic demographic and disease characteristics of cancer-diagnosed
      Syrian refugees treated in the border city of Turkey, Sanliurfa; a hospital-based
      retrospective case series study.
AB  - PURPOSE: Turkey hosts around 3 million Syrian refugees which is more than any
      other country in the world. Along with some other adaptation issues like
      cultural, language, and economic difficulties, significant problems in managing
      medical problems, chronic diseases like cancer in particular, have to be fixed.
      However, there are few studies which explore main patient and clinicopathological
      characteristics in Syrian refugees with cancer. The purpose of this study was to
      highlight the aforementioned characteristics along with management issues after
      cancer diagnosis of these patients. METHODS: This study was designed as a
      hospital-based retrospective observational case-series study of 134 Syrian
      refugees cancer patients between 2015 and 2017. RESULTS: The patient median age
      was 47.5 years (range 18- 80). Out of the 134, 102 (76.1%) were female. The most
      common cancer types were breast (n=57, 42.5%) and gynecological cancers (n=14,
      10.4%). The majority of patients were diagnosed at advanced stage (n=60, 44.8%).
      There were 91 (67.9%) and 43 (32.1%) patients admitted to our center from refugee
      camps and staying in a house, respectively. The median follow-up was 14 months
      (range 1-111) and 11 (8.2%) patients died. One and two-year survival rate of the
      whole group were 93% and 86%, respectively. There were 12 (9%) patients with
      grade 3-4 hematological and non-hematological toxicities. Neutropenia was the
      most common grade 3-4 toxicity (n=8, 6%). The patients staying in refugee camp (n
      91) or in a house (n=43) finished all planned cycles of chemotherapy with a rate
      of 71% (n=65) and 79% (n=34), respectively. Statistical analysis failed to show
      significant relationship between the staying site (either camp or house),
      chemotherapy compliance rate, grade 3-4 toxicities with p=0.347 and p=0.09,
      respectively. CONCLUSION: Our results revealed that breast cancer and
      gynecological cancers were the most common cancer types which are good candidates
      for cancer screening. Unfortunately, the majority of patients had cancer
      diagnosed at advanced stage. However, after diagnosis they could reach all health
      facilities including surgical operation, radiotherapy, and systemic chemotherapy
      similar to Turkish cancer patients. Therefore, our results suggested that major
      problem for the Syrian refugees adapting them into national screening program
      which may resulted that cancer diagnosis at earlier stage with high cure rate.

PMID- 29332359
TI  - Novel molecular and metabolic aspects in osteosarcoma.
AB  - Osteosarcoma (OS) is the most frequent bone-forming malignancy in children and
      adolescents. Concerning its molecular landscape, there is no a direct
      relationship with a specific gene, but a combination of genetic events. A broad
      spectrum of activated oncogenes and downregulated suppressor genes has been
      already explored and considered crucial for its progressive pathogenesis.
      Mechanisms of gene deregulation include amplifications, point mutations, allelic
      losses and also epigenetic abnormalities such as aberrant promoter methylation.
      Although a significant progress in understanding the molecular nature of the OS
      has been achieved, its aggressive phenotype - characterized by high metastatic
      potential - remains unexplored. Novel targeted therapeutic strategies include
      monoclonal antibodies (mABs) and also tyrosine-kinase inhibitors (TKIs).
      Additionally, sophisticated and innovative diagnostic techniques, such as 18
      fluorodeoxyglucose positron emission tomography plus CT (18F-FDG/PET/CT), provide
      critical data regarding its biological behavior. In the current paper, we present
      novel molecular and metabolic advances by analyzing OS genetic profile and
      biochemical microenvironment.

PMID- 29332360
TI  - From Fungus haematodes to Retinoblastoma.
AB  - Retinoblastoma is probably the only disease which received 40 different names
      until its official terminology which was adopted by the medical community in
      1926. The official record of retinoblastoma was reported in 1597 by Petrus Pawius
      (ca. 1564-1617). The development of pathology during the 19th century gave to
      opportunity to clarify the histological characteristics of the disease. Although
      in the past retinoblastoma was considered a fatal disease, nowadays with modern
      treatment the prognosis is better.

PMID- 29332361
TI  - Bisphosphonate-associated orbital inflammation: is it class-specific side effect?

PMID- 29332362
TI  - Association of non-Hodgkin's lymphoma with advanced endometriosis.

PMID- 29332363
TI  - A brain ependymoma with psychiatric manifestation.

PMID- 29332364
TI  - Medical errors done with good intention, according to the believes of the time in
      the past: oncology should be evidence-based nowadays.

PMID- 29332365
TI  - Positional errors in linear accelerator based frameless cranial stereotaxy: A
      note of caution.

PMID- 29332366
TI  - Molecular landscape in laryngeal chondrosarcoma.

PMID- 29332367
TI  - The role of tyrosine kinase inhibitors (TKIs) as adjuvant treatment for renal
      cancer. Where do we stand today?

PMID- 29332368
TI  - "Pearl oyster": a new ultrasonographic sign of the regressed testicular tumor.

PMID- 29332369
TI  - Preliminary testing of anthracycline-induced cardiotoxicity in children.

PMID- 29332370
TI  - Hallmarks in the evolution of gynaecological cancer surgery: the famous pioneers
      in children.
AB  - At the beginning of the 19th century, gynaecological cancer, mainly cancer of the
      uterus and cervix was a dreadful, incurable affection. However, the
      popularization of the three fundamentals in surgery, anesthesia, asepsis and
      haemostasis, ushered the golden age of operative gynaecology. During that period
      distinguished surgeons/gynaecologists such as Friedrich Benjamin Osiander (1759
      1822), Elias von Siebold (1775-1828) and Joseph-Claude-Anthelme Recamier (1774
      1852) contributed to the development of the operative techniques, providing a
      therapeutic solution in gynaecological cancer.

PMID- 29332372
TI  - Measurement and modeling of indoor radon concentrations in residential buildings.
AB  - Radon, the primary constituent of natural radiation, is the second leading
      environmental cause of lung cancer after smoking. To confirm a relationship
      between indoor radon exposure and lung cancer, estimating cumulative levels of
      exposure to indoor radon for an individual or population is necessary. This study
      sought to develop a model for estimate indoor radon concentrations in Korea.
      Especially, our model and method may have wider application to other residences,
      not to specific site, and can be used in situations where actual measurements for
      input variables are lacking. In order to develop a model, indoor radon
      concentrations were measured at 196 ground floor residences using passive alpha
      track detectors between January and April 2016. The arithmetic mean (AM) and
      geometric mean (GM) means of indoor radon concentrations were 117.86+/-72.03 and
      95.13+/-2.02 Bq/m3, respectively. Questionnaires were administered to assess the
      characteristics of each residence, the environment around the measuring
      equipment, and lifestyles of the residents. Also, national data on indoor radon
      concentrations at 7643 detached houses for 2011-2014 were reviewed to determine
      radon concentrations in the soil, and meteorological data on temperature and wind
      speed were utilized to approximate ventilation rates. The estimated ventilation
      rates and radon exhalation rates from the soil varied from 0.18 to 0.98/hr (AM,
      0.59+/-0.17/hr) and 326.33 to 1392.77 Bq/m2/hr (AM, 777.45+/-257.39; GM, 735.67+/
      1.40 Bq/m2/hr), respectively. With these results, the developed model was applied
      to estimate indoor radon concentrations for 157 residences (80% of all 196
      residences), which were randomly sampled. The results were in better agreement
      for Gyeonggi and Seoul than for other regions of Korea. Overall, the actual and
      estimated radon concentrations were in better agreement, except for a few low
      concentration residences.

PMID- 29332373
TI  - Use of adverse outcome pathways in chemical toxicity testing: potential
      advantages and limitations.
AB  - Amid revolutionary changes in toxicity assessment brought about by increasing
      regulation of chemicals, adverse outcome pathways (AOPs) have emerged as a useful
      framework to assess adverse effect of chemicals using molecular level effect,
      which aid in setting environmental regulation policies. AOPs are biological maps
      that describe mechanisms linking molecular initiating event to adverse outcomes
      (AOs) at an individual level. Each AOP consists of a molecular initiating event,
      key events, and an AO. AOPs use molecular markers to predict endpoints currently
      used in risk assessment, promote alternatives to animal model-based test methods,
      and provide scientific explanations for the effects of chemical exposures.
      Moreover, AOPs enhance certainty in interpreting existing and new information.
      The application of AOPs in chemical toxicity testing will help shift the existing
      paradigm of chemical management based on apical endpoints toward active
      application of in silico and in vitro data.

PMID- 29332375
TI  - Recurrent aphtous stomatitis.
AB  - Recurrent aphtous stomatitis (recurrent aphtous ulcers, canker sores) is the most
      common ulcerative disease of the oral mucosa. In this paper we presented the main
      clinical features, epidemiologic data, etiopathogenetic factors and clinical
      management, based on the current medical literature reports.

PMID- 29332374
TI  - Transcatheter aortic valve replacement in bicuspid aortic valve stenosis: where
      do we stand?
AB  - Bicuspid aortic valve is the most common congenital cardiac defect in adults, and
      symptom typically develops in adulthood. In the majority of cases, bicuspid
      aortic valve disease progress with ages and surgical aortic valve replacement is
      performed with excellent operative outcomes. However, with the relatively slow
      progression of disease, surgical aortic valve replacement is required in elderly
      patients but the surgical risk often deemed extremely high due to old age and
      multiple comorbidities. Transcatheter aortic valve replacement (TAVR) has evolved
      from a novel technology to an established therapy for intermediate- and high-risk
      patients with symptomatic severe aortic valve stenosis (AS). Numerous studies
      have demonstrated the safety and efficacy of TAVR, and more than 250,000 patients
      have been treated with this technology. Although randomized trials have
      established TAVR as the standard treatment, these trials excluded congenital
      bicuspid AS due to its unique morphological features. Nevertheless, the growing
      experience, accumulated knowledge, and advancements of new technology lead to the
      expand use of TAVR to other pathologies or other populations such as bicuspid AS.
      With integration of imaging multimodalities (computed tomography and
      echocardiography), the diagnosis and classification of bicuspid aortic valve has
      been changing. Due to unfavorable anatomic features of bicuspid AS, the outcomes
      of TAVR in bicuspid AS was suboptimal, particularly when using the first
      generation transcatheter valves. However, the newer-generation transcatheter
      valves significantly improved the outcomes of TAVR in bicuspid AS. Nonetheless,
      several issues still remain to be resolved. Given longer life expectancy in
      patients with bicuspid AS undergoing TAVR, durability of transcatheter valves is
      concerned. In addition, patients with bicuspid aortic valves often have
      concomitant dilatation of proximal part of ascending aorta (aortopathy), but
      limited data exist about the clinical prognosis of bicuspid aortic valve with
      concomitant aortopathy in elderly patients. Considering the expanding indication
      of TAVR to lower surgical risk and younger population, these issues should be
      evaluated in future studies.

PMID- 29332378
TI  - Role of psoriasis on subclinical cardiovascular disease.

PMID- 29332379
TI  - Correlation among atherosclerosis, cardiac and respiratory function in subjects
      with cystic fibrosis.

PMID- 29332377
TI  - Comparisons of three different doses of alirocumab application in patients with
      hypercholesterolemia: a meta-analysis.
AB  - INTRODUCTION: Low high-density lipoprotein cholesterol (HDL-C) and high low
      density lipoprotein cholesterol (LDL-C) levels are associated with incidence of
      cardiovascular disease (CVD). Alirocumab has been considered as an efficacious,
      safe and promising therapeutic modality for hypercholesterolemia. The purpose of
      this study is to compare the differences of the three different doses of
      alirocumab in patients with hypercholesterolemia. EVIDENCE ACQUISITION:
      Randomized controlled trials were identified from PubMed, EMBASE, PMC and
      Cochrane-library databases. The inter-comparison of different doses were
      performed by subgroups analysis. Meta-analyses were performed by the Review
      Manager 5.3 and STATA 13.0 software. EVIDENCE SYNTHESIS: A total of nine studies
      involving 3870 patients were included in this meta-analysis. Alirocumab
      administered at 75-150 mg every 2 weeks (Q2W) resulted in a greater percent
      change from baseline in LDL-C concentrations (MD, -55.17; 95% CI: -64.35 to 
      45.99; P<0.05), and HDL-C levels (MD, 7.70; 95% CI 5.94 to 9.46; P<0.05) than
      other two doses (300 mg every 4 weeks [Q4W], 150 mg every 2 weeks [Q2W]). There
      was no difference in achieving the treatment goal of LDL-C (<=1.8 mmol/L), in
      other serum lipid parameters (total cholesterol [TC], triglyceride [TG]), and in
      the incidence of adverse events. CONCLUSIONS: The results demonstrate that
      alirocumab at a dose of 75-150 mg Q2W should be preferred in patients with
      hypercholesterolemia.

PMID- 29332376
TI  - New and emerging treatments for metastatic Merkel cell carcinoma.

PMID- 29332380
TI  - Solvent Modulation of Aromatic Substituent Effects in Molecular Balances
      Controlled by CH-pi Interactions.
AB  - CH-pi aromatic interactions are ubiquitous in nature and are capable of
      regulating important chemical and biochemical processes. Solvation and aromatic
      substituent effects are known to perturb the CH-pi aromatic interactions.
      However, the nature by which the two factors influence one another is relatively
      unexplored. Here we demonstrate experimentally that there is a quantitative
      correlation between substituent effects in CH-pi interactions and the hydrogen
      bond acceptor constants of the solvating molecule. The CH-pi interaction energies
      were measured by the conformational study of a series of aryl-substituted
      molecular balances in which the conformational preferences depended on the
      relative strengths of the methyl and aryl CH-pi interactions in the folded and
      unfolded states, respectively. Due to the favorable methyl-aromatic interactions,
      the balances were found to exist predominantly in the folded state. The observed
      substituent effect in the conformational preferences of the balances was
      controlled by the explicit solvation/desolvation of the aryl proton. The
      interpretation of the conformational free energy as a function of substituents
      and solvation using Hunter's solvation model revealed that a linear relationship
      exists between the sensitivity of aromatic substituent effects (i.e., the rho
      values derived from Hammett plots) and the hydrogen-bond acceptor propensity
      (betas) of the solvent molecule: rho = 0.06betas - 0.04.

PMID- 29332381
TI  - Significant Role of Mg Stoichiometry in Designing High Thermoelectric Performance
      for Mg3(Sb,Bi)2-Based n-Type Zintls.
AB  - Complex structures with versatile chemistry provide considerable chemical
      tunability of the transport properties. Good thermoelectric materials are
      generally extrinsically doped semiconductors with optimal carrier concentrations,
      while charged intrinsic defects (e.g., vacancies, interstitials) can also adjust
      the carriers, even in the compounds with no apparent deviation from a
      stoichiometric nominal composition. Here we report that in Zintl compounds
      Mg3+xSb1.5Bi0.5, the carrier concentration can be tuned from p-type to n-type by
      simply altering the initial Mg concentration. The spherical-aberration-corrected
      (CS-corrected) high-angle annular dark field scanning transmission electron
      microscopy (HAADF-STEM) and energy-dispersive X-ray spectroscopy (EDX) mapping
      analysis show that the excess Mg would form a separate Mg-rich phase after Mg
      vacancies have been essentially compensated. Additionally, a slight Te doping at
      Bi site on Mg3.025Sb1.5Bi0.5 has enabled good n-type thermoelectric properties,
      which is comparable to the Te-doped Mg-rich sample. The actual final composition
      of Mg3.025Sb1.5Bi0.5 analyzed by EPMA is also close to the stoichiometry
      Mg3Sb1.5Bi0.5, answering the open question whether excess Mg is prerequisite to
      realize exceptionally high n-type thermoelectric performance by different sample
      preparation methods. The motivation for this work is first to understand the
      important role of vacancy and then to guide for discovering more promising n-type
      Zintl thermoelectric materials.

PMID- 29332382
TI  - Cu2I2Se6: A Metal-Inorganic Framework Wide-Bandgap Semiconductor for Photon
      Detection at Room Temperature.
AB  - Cu2I2Se6 is a new wide-bandgap semiconductor with high stability and great
      potential toward hard radiation and photon detection. Cu2I2Se6 crystallizes in
      the rhombohedral R3m space group with a density of d = 5.287 g.cm-3 and a wide
      bandgap Eg of 1.95 eV. First-principles electronic band structure calculations at
      the density functional theory level indicate an indirect bandgap and a low
      electron effective mass me* of 0.32. The congruently melting compound was grown
      in centimeter-size Cu2I2Se6 single crystals using a vertical Bridgman method. A
      high electric resistivity of ~1012 Omega.cm is readily achieved, and detectors
      made of Cu2I2Se6 single crystals demonstrate high photosensitivity to Ag Kalpha X
      rays (22.4 keV) and show spectroscopic performance with energy resolutions under
      241Am alpha-particles (5.5 MeV) radiation. The electron mobility is measured by a
      time-of-flight technique to be ~46 cm2.V-1.s-1. This value is comparable to that
      of one of the leading gamma-ray detector materials, TlBr, and is a factor of 30
      higher than mobility values obtained for amorphous Se for X-ray detection.

PMID- 29332383
TI  - Developing Pantetheinase-Resistant Pantothenamide Antibacterials: Structural
      Modification Impacts on PanK Interaction and Mode of Action.
AB  - Pantothenamides (PanAms) are analogues of pantothenate, the biosynthetic
      precursor of coenzyme A (CoA), and show potent antimicrobial activity against
      several bacteria and the malaria parasite in vitro. However, pantetheinase
      enzymes that normally degrade pantetheine in human serum also act on the PanAms,
      thereby reducing their potency. In this study, we designed analogues of the known
      antibacterial PanAm N-heptylpantothenamide (N7-Pan) to be resistant to
      pantetheinase by using three complementary structural modification strategies. We
      show that, while two of these are effective in imparting resistance, the
      introduced modifications have an impact on the analogues' interaction with
      pantothenate kinase (PanK, the first CoA biosynthetic enzyme), which acts as a
      metabolic activator and/or target of the PanAms. This, in turn, directly affects
      their mode of action. Importantly, we discover that the phosphorylated version of
      N7-Pan shows pantetheinase resistance and antistaphylococcal activity, providing
      a lead for future studies in the ongoing search of PanAm analogues that show in
      vivo efficacy.

PMID- 29332384
TI  - Structure of Lipid Nanoparticles Containing siRNA or mRNA by Dynamic Nuclear
      Polarization-Enhanced NMR Spectroscopy.
AB  - Here, we show how dynamic nuclear polarization (DNP) NMR spectroscopy experiments
      permit the atomic level structural characterization of loaded and empty lipid
      nanoparticles (LNPs). The LNPs used here were synthesized by the microfluidic
      mixing technique and are composed of ionizable cationic lipid (DLin-MC3-DMA), a
      phospholipid (distearoylphosphatidylcholine, DSPC), cholesterol, and
      poly(ethylene glycol) (PEG) (dimyristoyl phosphatidyl ethanolamine (DMPE)-PEG
      2000), as well as encapsulated cargoes that are either phosphorothioated siRNA
      (50 or 100%) or mRNA. We show that LNPs form physically stable complexes with
      bioactive drug siRNA for a period of 94 days. Relayed DNP experiments are
      performed to study 1H-1H spin diffusion and to determine the spatial location of
      the various components of the LNP by studying the average enhancement factors as
      a function of polarization time. We observe a striking feature of LNPs in the
      presence and in the absence of encapsulating siRNA or mRNA by comparing our
      experimental results to numerical spin-diffusion modeling. We observe that LNPs
      form a layered structure, and we detect that DSPC and DMPE-PEG 2000 lipids form a
      surface rich layer in the presence (or absence) of the cargoes and that the
      cholesterol and ionizable cationic lipid are embedded in the core. Furthermore,
      relayed DNP 31P solid-state NMR experiments allow the location of the cargo
      encapsulated in the LNPs to be determined. On the basis of the results, we
      propose a new structural model for the LNPs that features a homogeneous core with
      a tendency for layering of DSPC and DMPE-PEG at the surface.

PMID- 29332385
TI  - Highly Sensitive Ratiometric Self-Assembled Micellar Nanoprobe for Nitroxyl and
      Its Application In Vivo.
AB  - Nitroxyl (HNO) is a derivative of nitric oxide (NO) that plays an essential role
      in various biological and pharmacological events. Until now, the in situ trapping
      and specific detection of HNO in living samples is still challenging. In this
      project, we fabricated a novel BODIPY-based micellar nanoprobe for monitoring
      nitroxyl in vitro and in vivo in ratiometric mode in aqueous solution. The probe
      (P-BODIPY-N) contains an asymmetrical BODIPY dye for fluorescent signaling and a
      diphenylphosphinobenzoyl as the trigger moiety; then we encapsulated P-BODIPY-N
      into the hydrophobic interior of an amphiphilic copolymer (mPEG-DSPE) and
      prepared a novel BODIPY-based micellar nanoprobe: NP-BODIPY-N. As far as we know,
      this probe is the first reported ratiometric fluorescent nanoprobe for HNO, which
      exhibits ultrasensitivity, high selectivity, and good biocompatibility. Above
      all, this nanoprobe shows favorable cellular uptaken and was successfully used to
      detect intracellular HNO released by Angeli's salt in living cells and zebrafish
      larvae. These results indicate that our newly designed nanoprobe will provide a
      promising tool for the studies of HNO in living system.

PMID- 29332386
TI  - Multiple yet Controllable Photoswitching in a Single AIEgen System.
AB  - Seeking new methods to obtain elaborate artificial on-demand photoswitching with
      multiple functionalities remains challenging. Most of the systems reported so far
      possess only one specific function and their nonemissive nature in the aggregated
      state inevitably limit their applications. Herein, a tailored cyanostilbene-based
      molecule with aggregation-induced emission characteristic was synthesized and was
      found to exhibit efficient, multiple and controllable photoresponsive behaviors
      under different conditions. Specifically, three different reactions were
      involved: (i) reversible Z/E isomerization under room light and thermal treatment
      in CH3CN, (ii) UV-induced photocyclization with a concomitant dramatic
      fluorescence enhancement, and (iii) regio- and stereoselective photodimerization
      in aqueous medium with microcrystal formation. Experimental and theoretical
      analyses gave visible insights and detailed mechanisms of the photoreaction
      processes. Fluorescent 2D photopattern with enhanced signal-to-background ratio
      was fabricated based on the controllable "turn-on" and "turn-off" photobehaviors
      in different states. The present study thus paves an easy yet efficient way to
      construct smart multiphotochromes for unique applications.

PMID- 29332388
TI  - Immersion and Contact Efflorescence Induced by Mineral Dust Particles.
AB  - The phase state of inorganic salt aerosols impacts their properties, including
      the ability to undergo hygroscopic growth, catalyze heterogeneous reactions, and
      act as cloud condensation nuclei. Here, we report the first observation of
      contact efflorescence by mineral dust aerosol. The efflorescence of aqueous
      ammonium sulfate ((NH4)2SO4) and sodium chloride (NaCl) droplets by contact with
      three types of mineral dust particles (illite, montmorillonite, and NX illite),
      were examined using an optical levitation chamber. Immersion mode efflorescence
      was also studied for comparison. We find that in the presence of mineral dust
      particles, crystallization occurred at a higher relative humidity (RH) when
      compared to the homogeneous phase transition. Additionally, crystallization by
      contact mode efflorescence occurred at a higher RH than the corresponding
      immersion mode. Crystallization efficiencies in the contact mode exhibited an ion
      specific trend consistent with the Hoffmeister series. Estimates for lifetimes of
      a salt droplet to collide with dust particles suggests that collisions between
      the two aerosol types are likely to occur before the salt aerosol is removed by
      other atmospheric processes. Such collisions could then lead to the
      crystallization of salt droplets that would otherwise have remained liquid,
      changing the overall impact that salt aerosols have on atmospheric chemistry and
      climate.

PMID- 29332389
TI  - Direct Catalytic Asymmetric Mannich-Type Reaction en Route to alpha-Hydroxy-beta
      amino Acid Derivatives.
AB  - A direct catalytic Mannich-type reaction of alpha-oxygen-functionalized amides
      was achieved. The use of 7-azaindoline amide was crucial to facilitate direct
      enolization and subsequent stereoselective addition to imines in a cooperative
      catalytic system comprising a soft Lewis acid and Bronsted base. The
      operationally simple room-temperature protocol furnished a syn-Mannich adduct
      with high stereoselectivity. Divergent functional group transformation of the
      amide moiety of the product allowed for expeditious access to enantioenriched syn
      configured alpha-hydroxy-beta-amino carboxylic acid derivatives, highlighting the
      synthetic utility of the present catalysis.

PMID- 29332387
TI  - Proteome-Wide Characterization of Phosphorylation-Induced Conformational Changes
      in Breast Cancer.
AB  - Because of the close link between protein function and protein folding stability,
      knowledge about phosphorylation-induced protein folding stability changes can
      lead to a better understanding of the functional effects of protein
      phosphorylation. Here, the stability of proteins from rates of oxidation (SPROX)
      and limited proteolysis (LiP) techniques are used to compare the conformational
      properties of proteins in two MCF-7 cell lysates including one that was and one
      that was not dephosphorylated with alkaline phosphatase. A total of 168 and 251
      protein hits were identified with dephosphorylation-induced stability changes
      using the SPROX and LiP techniques, respectively. Many protein hits are
      previously known to be differentially phosphorylated or differentially stabilized
      in different human breast cancer subtypes, suggesting that the phosphorylation
      induced stability changes detected in this work are disease related. The SPROX
      hits were enriched in proteins with aminoacyl-tRNA ligase activity. These
      enriched protein hits included many aminoacyl-tRNA synthetases (aaRSs), which are
      known from previous studies to have their catalytic activity modulated by
      phosphorylation. The SPROX results revealed that the magnitudes of the
      destabilizing effects of dephoshporylation on the different aaRSs were directly
      correlated with their previously reported aminoacylation activity change upon
      dephosphorylation. This substantiates the close link between protein folding and
      function.

PMID- 29332390
TI  - High Drug Loading and Sub-Quantitative Loading Efficiency of Polymeric Micelles
      Driven by Donor-Receptor Coordination Interactions.
AB  - Polymeric micelles are extensively used for the delivery of hydrophobic drugs,
      which, however, suffer from unsatisfactory drug loading, colloidal uniformity,
      formulation stability, and drug release. Herein, we demonstrate a convenient
      strategy to prepare micelles with ultrahigh drug loading via the incorporation of
      polymer-drug coordination interactions. An amphiphilic copolymer containing
      pendant phenylboronic acid as electron acceptor unit was synthesized, which
      afforded donor-acceptor coordination with doxorubicin to obtain micelles with
      ultrahigh drug loading (~50%), nearly quantitative loading efficiency (>95%),
      uniform size, and colloidal stability. Besides, the encapsulated drug can be
      effectively and selectively released in response to the high reactive oxygen
      species levels in cancer cells, which potentiated the anticancer efficacy and
      reduced systemic toxicity. Apart from doxorubicin, the current platform could be
      extended to other drugs with electron-donating groups (e.g., epirubicin and
      irinotecan), rendering a simple and robust strategy for enabling high drug
      loading in polymeric micelles and cancer-specific drug release.

PMID- 29332391
TI  - Interconversion of Methyltropyl and Xylyl Radicals: A Pathway Unavailable to the
      Benzyl-Tropyl Rearrangement.
AB  - The products of an electrical discharge containing toluene are interrogated using
      resonance-enhanced multiphoton ionization and laser-induced fluorescence
      spectroscopies. A previously unreported electronic spectrum recorded at m/z =
      105, with a putative origin band at 26053 cm-1, is assigned to methyltropyl
      radical, which appears to be a major product of the toluene discharge, plausibly
      arising from CH insertion. All three o-, m-, and p-xylyl isomers are also
      identified. These isomers are detected in electrical discharges containing
      various xylenes, where it is also found that interconversion occurs: A discharge
      of o-xylene produces some m-xylyl; a discharge of m-xylene produces some o-xylyl;
      and a discharge of p-xylene produces all three isomers. No alpha-methylbenzyl was
      detected, but styrene was. These observations are supported by state-of-the-art
      quantum chemical calculations, which reveal an isomerization pathway between
      methyltropyl and xylyl radicals for which there is no analogue in the canonical
      tropyl-benzyl isomerization.

PMID- 29332392
TI  - Transfer Hydrogenation of Aldehydes and Ketones with Isopropanol under Neutral
      Conditions Catalyzed by a Metal-Ligand Bifunctional Catalyst [Cp*Ir(2,2'
      bpyO)(H2O)].
AB  - A Cp*Ir complex bearing a functional bipyridonate ligand [Cp*Ir(2,2'-bpyO)(H2O)]
      was found to be a highly efficient and general catalyst for transfer
      hydrogenation of aldehydes and chemoselective transfer hydrogenation of
      unsaturated aldehydes with isopropanol under neutral conditions. It was
      noteworthy that many readily reducible or labile functional groups such as nitro,
      cyano, ester, and halide did not undergo any change under the reaction
      conditions. Furthermore, this catalytic system exhibited high activity for
      transfer hydrogenation of ketones with isopropanol. Notably, this research
      exhibited new potential of metal-ligand bifunctional catalysts for transfer
      hydrogenation.

PMID- 29332393
TI  - Impact of Nonideal Nanoparticles on X-ray Photoelectron Spectroscopic
      Quantitation: An Investigation Using Simulation and Modeling of Gold
      Nanoparticles.
AB  - Quantitative X-ray photoelectron spectroscopic (XPS) analysis combined with
      spectral modeling of photoelectrons can be valuable while investigating the
      surface chemistry of nanoparticles (NPs) with different morphologies. Herein,
      with the use of NIST Simulation of Electron Spectra for Surface Analysis (SESSA),
      a comparative analysis of experimental and simulated photoelectron peak
      intensities in gold nanoparticles (AuNPs) of different morphologies is presented.
      Three sets of supported AuNPs with different morphologies were selected from a
      series of as synthesized Au-TiO2 catalyst samples. Using transmission electron
      microscopy (TEM) analyzed morphological information on the AuNPs as input model
      parameters in SESSA, XPS spectra were generated from the respective input NP
      morphologies. A degree of greater mismatch between SESSA simulated and
      experimental XPS spectra was observed while using the TEM obtained average
      diameter of the nanoparticles. The degree of mismatch lowered when the true
      nonspherical shape of the nanoparticles as obtained from TEM images was taken
      into account for the simulation. This demonstrates the impact of surface
      morphology on the XPS peak intensities which needs to be incorporated to obtain
      precise quantified information from the supported nanoparticles. This work
      demonstrates the applicability of SESSA in combination with experimental XPS and
      TEM measurements for precise quantification of XPS spectra from complex, nonideal
      shaped nanoparticles. This study can be extended to include a broad range of
      nanoparticles with ideal or nonideal geometries, thus providing a simple method
      to utilize quantitative XPS analysis to a wide range of nanomaterials.

PMID- 29332394
TI  - Compositional Dependence of Solubility/Retention of Molybdenum Oxides in
      Aluminoborosilicate-Based Model Nuclear Waste Glasses.
AB  - Molybdenum oxides are an integral component of the high-level waste streams being
      generated from the nuclear reactors in several countries. Although borosilicate
      glass has been chosen as the baseline waste form by most of the countries to
      immobilize these waste streams, molybdate oxyanions (MoO42-) exhibit very low
      solubility (~1 mol %) in these glass matrices. In the past three to four decades,
      several studies describing the compositional and structural dependence of
      molybdate anions in borosilicate and aluminoborosilicate glasses have been
      reported in the literature, providing a basis for our understanding of
      fundamental science that governs the solubility and retention of these species in
      the nuclear waste glasses. However, there are still several open questions that
      need to be answered to gain an in-depth understanding of the mechanisms that
      control the solubility and retention of these oxyanions in glassy waste forms.
      This article is focused on finding answers to two such questions: (1) What are
      the solubility and retention limits of MoO3 in aluminoborosilicate glasses as a
      function of chemical composition? (2) Why is there a considerable increase in the
      solubility of MoO3 with incorporation of rare-earth oxides (for example, Nd2O3)
      in aluminoborosilicate glasses? Accordingly, three different series of
      aluminoborosilicate glasses (compositional complexity being added in a tiered
      approach) with varying MoO3 concentrations have been synthesized and
      characterized for their ability to accommodate molybdate ions in their structure
      (solubility) and as a glass-ceramic (retention). The contradictory viewpoints
      (between different research groups) pertaining to the impact of rare-earth
      cations on the structure of aluminoborosilicate glasses are discussed, and their
      implications on the solubility of MoO3 in these glasses are evaluated. A novel
      hypothesis explaining the mechanism governing the solubility of MoO3 in rare
      earth containing aluminoborosilicate glasses has been proposed.

PMID- 29332395
TI  - Structure and Reactivity of Half-Sandwich Rh(+3) and Ir(+3) Carbene Complexes.
      Catalytic Metathesis of Azobenzene Derivatives.
AB  - Traditional rhodium carbene chemistry relies on the controlled decomposition of
      diazo derivatives with [Rh2(OAc)4] or related dinuclear Rh(+2) complexes, whereas
      the use of other rhodium sources is much less developed. It is now shown that
      half-sandwich carbene species derived from [Cp*MX2]2 (M = Rh, Ir; X = Cl, Br, I,
      Cp* = pentamethylcyclopentadienyl) also exhibit favorable application profiles.
      Interestingly, the anionic ligand X proved to be a critical determinant of
      reactivity in the case of cyclopropanation, epoxide formation and the previously
      unknown catalytic metathesis of azobenzene derivatives, whereas the nature of X
      does not play any significant role in -OH insertion reactions. This perplexing
      disparity can be explained on the basis of spectral and crystallographic data of
      a representative set of carbene complexes of this type, which could be isolated
      despite their pronounced electrophilicity. Specifically, the donor/acceptor
      carbene 10a derived from ArC(?N2)COOMe and [Cp*RhCl2]2 undergoes spontaneous 1,2
      migratory insertion of the emerging carbene unit into the Rh-Cl bond with
      formation of the C-metalated rhodium enolate 11. In contrast, the analogous
      complexes 10b,c derived from [Cp*RhX2]2 (X = Br, I) as well as the iridium
      species 13 and 14 derived from [Cp*IrCl2]2 are sufficiently stable and allow true
      carbene reactivity to be harnessed. These complexes are competent intermediates
      for the catalytic metathesis of azobenzene derivatives, which provides access to
      alpha-imino esters that would be difficult to make otherwise. Rather than
      involving metal nitrenes, the reaction proceeds via aza-ylides that evolve into
      diaziridines; a metastable compound of this type has been fully characterized.

PMID- 29332396
TI  - Electrochemical System for the Study of Trans-Plasma Membrane Electron Transport
      in Whole Eukaryotic Cells.
AB  - The study of trans-plasma membrane electron transport (tPMET) in oncogenic
      systems is paramount to the further understanding of cancer biology. The current
      literature provides methodology to study these systems that hinges upon
      mitochondrial knockout genotypes in conjunction with cell surface oxygen
      consumption, or the detection of an electron acceptor using colorimetric methods.
      However, when using an iron redox based system to probe tPMET, there is yet to be
      a method that allows for the simultaneous quantification of iron redox states
      while providing an exceptional level of sensitivity. Developing a method to
      simultaneously analyze the redox state of a reporter molecule would give
      advantages in probing the underlying biology. Herein, we present an
      electrochemical based method that allows for the quantification of both
      ferricyanide and ferrocyanide redox states to a highly sensitive degree. We have
      applied this system to a novel application of assessing oncogenic cell-driven
      iron reduction and have shown that it can effectively quantitate and identify
      differences in iron reduction capability of three lung epithelial cell lines.

PMID- 29332397
TI  - Unconventional Fragment Usage Enables a Concise Total Synthesis of (-)
      Callyspongiolide.
AB  - An asymmetric synthesis of (-)-callyspongiolide is described. The route builds
      the macrolide domain atypically from a disaccharide and a monoterpene without
      passing through a seco-acid. Chiral iridium catalysis selectively joins
      fragments. Subsequent degradation of an imbedded butyrolactone via perhemiketal
      fragmentation affords a stereo- and regio-defined homoallylic alcohol that is
      engaged directly in a carbonylative macrolactonization. Further elaboration of
      the polyunsaturated appendage provides the natural product in a particularly
      direct and flexible manner.

PMID- 29332398
TI  - High-Performance Thermoelectric Bulk Colusite by Process Controlled Structural
      Disordering.
AB  - High-performance thermoelectric bulk sulfide with the colusite structure is
      achieved by controlling the densification process and forming short-to-medium
      range structural defects. A simple and powerful way to adjust carrier
      concentration combined with enhanced phonon scattering through point defects and
      disordered regions is described. By combining experiments with band structure and
      phonons calculations, we elucidate, for the first time, the underlying mechanism
      at the origin of intrinsically low thermal conductivity in colusite samples as
      well as the effect of S vacancies and antisite defects on the carrier
      concentration. Our approach provides a controlled and scalable method to engineer
      high power factors and remarkable figures of merit near the unity in complex bulk
      sulfide such as Cu26V2Sn6S32 colusites.

PMID- 29332399
TI  - ENDOR-Induced EPR of Disordered Systems: Application to X-Irradiated Alanine.
AB  - The electron paramagnetic resonance (EPR) spectra of radiation-induced radicals
      in organic solids are generally composed of multiple components that largely
      overlap due to their similar weak g anisotropy and a large number of hyperfine
      (HF) interactions. Such properties make these systems difficult to study using
      standard cw EPR spectroscopy even in single crystals. Electron-nuclear double
      resonance (ENDOR) spectroscopy is a powerful and widely used complementary
      technique. In particular, ENDOR-induced EPR (EIE) experiments are useful for
      separating the overlapping contributions. In the present work, these techniques
      were employed to study the EPR spectrum of stable radicals in X-irradiated
      alanine, which is widely used in dosimetric applications. The principal values of
      all major proton HF interactions of the dominant radicals were determined by
      analyzing the magnetic field dependence of the ENDOR spectrum at 50 K, where the
      rotation of methyl groups is frozen. Accurate simulations of the EPR spectrum
      were performed after the major components were separated using an EIE analysis.
      As a result, new evidence in favor of the model of the second dominant radical
      was obtained.

PMID- 29332400
TI  - Multiscale Kinetic Modeling Reveals an Ensemble of Cl-/H+ Exchange Pathways in
      ClC-ec1 Antiporter.
AB  - Despite several years of research, the ion exchange mechanisms in chloride/proton
      antiporters and many other coupled transporters are not yet understood at the
      molecular level. Here, we present a novel approach to kinetic modeling and apply
      it to ion exchange in ClC-ec1. Our multiscale kinetic model is developed by (1)
      calculating the state-to-state rate coefficients with reactive and polarizable
      molecular dynamics simulations, (2) optimizing these rates in a global kinetic
      network, and (3) predicting new electrophysiological results. The model shows
      that the robust Cl:H exchange ratio (2.2:1) can indeed arise from kinetic
      coupling without large protein conformational changes, indicating a possible
      facile evolutionary connection to chloride channels. The E148 amino acid residue
      is shown to couple chloride and proton transport through protonation-dependent
      blockage of the central anion binding site and an anion-dependent pKa value,
      which influences proton transport. The results demonstrate how an ensemble of
      different exchange pathways, as opposed to a single series of transitions,
      culminates in the macroscopic observables of the antiporter, such as transport
      rates, chloride/proton stoichiometry, and pH dependence.

PMID- 29332401
TI  - Proteomic Profiling of Leishmania donovani Promastigote Subcellular Organelles.
AB  - To facilitate a greater understanding of the biological processes in the
      medically important Leishmania donovani parasite, a combination of differential
      and density-gradient ultracentrifugation techniques were used to achieve a
      comprehensive subcellular fractionation of the promastigote stage. An in-depth
      label-free proteomic LC-MS/MS analysis of the density gradients resulted in the
      identification of ~50% of the Leishmania proteome (3883 proteins detected), which
      included ~645 integral membrane proteins and 1737 uncharacterized proteins.
      Clustering and subcellular localization of proteins was based on a subset of
      training Leishmania proteins with known subcellular localizations that had been
      determined using biochemical, confocal microscopy, or immunoelectron microscopy
      approaches. This subcellular map will be a valuable resource that will help
      dissect the cell biology and metabolic processes associated with specific
      organelles of Leishmania and related kinetoplastids.

PMID- 29332402
TI  - Monitoring Antimicrobial Mechanisms of Surface-Immobilized Peptides in Situ.
AB  - Antimicrobial peptides (AMPs) in free solution can kill bacteria by disrupting
      bacterial cell membranes. Their modes of action have been extensively studied,
      and various models ranging from pore formation to carpet-like mechanisms were
      proposed. Surface-immobilized AMPs have been used as coatings to kill bacteria
      and as sensors to capture bacteria, but the interaction mechanisms of surface
      immobilized AMPs and bacteria are not fully understood. In this research, an
      analytical platform, sum frequency generation (SFG) microscope, which is composed
      of an SFG vibrational spectrometer and a fluorescence microscope, was used to
      probe molecular interactions between surface-immobilized AMPs and bacteria in
      situ in real time at the solid/liquid interface. SFG probed the molecular
      structure of surface-immobilized AMPs while interacting with bacteria, and
      fluorescence images of dead bacteria were monitored as a function of time during
      the peptide-bacteria interaction. It was believed that upon bacteria contact, the
      surface-immobilized peptides changed their orientation and killed bacteria. This
      research demonstrated that the SFG microscope platform can examine the structure
      and function (bacterial killing) at the same time in the same sample environment,
      providing in-depth understanding on the structure-activity relationships of
      surface-immobilized AMPs.

PMID- 29332403
TI  - A rare complication after colonoscopy: a splenic rupture.
AB  - Colonoscopy is the gold standard for the study of colorectal pathology. Splenic
      injury is a rare but potentially fatal complication to consider. Therefore, we
      present two cases whose management was different and we show their clinical
      presentation, their diagnosis and their treatment in order to recognize this
      complication early to establish early treatment.

PMID- 29332404
TI  - Bowel obstruction secondary to deep infiltrating endometriosis of the ileum.
AB  - Deep infiltrating endometriosis (DIE) of the ileum is an uncommon lesion that may
      be severe in its clinical presentation. Its diagnosis is challenging in the
      absence of a gynecological history of endometriosis and because of its anatomical
      location. We read the article by Sanchez, Candel, and Albarracin, and now report
      an additional case that was managed urgently.

PMID- 29332405
TI  - Endoscopic ultrasound-guided choledochoduodenostomy after a failed or impossible
      ERCP.
AB  - INTRODUCTION: endoscopic ultrasound-guided biliary drainage (EUS-BD) is an
      alternative to percutaneous trans-hepatic biliary drainage (PTBD) in cases of
      failed endoscopic retrograde cholangiopancreatography (ERCP). METHODS: this is a
      retrospective description of six cases of endoscopic ultrasound-guided biliary
      drainage via choledochoduodenostomy (EUCD), as well as the clinical
      characteristics, endoscopic procedure, complications and monitoring. RESULTS: all
      cases had malignant distal biliary obstruction. The procedure was concluded with
      good drainage in four out of six patients. Two late complications were recorded
      that were caused by stent migration and there were no deaths related with the
      procedure. The average monitoring period was six months. CONCLUSIONS: EUCD can be
      considered as a valid therapeutic choice in some selected cases and when
      performed by a team of expert endoscopists in cases of failed ERCP drainage or as
      an alternative to PTBD. However, the procedure has some associated complications.

PMID- 29332406
TI  - The morphological and functional diagnosis of a rare entity: lipomatous
      pseudohypertrophy of the pancreas.
AB  - Lipomatous pseudohypertrophy of the pancreas is a rare entity characterized by a
      replacement, focal or diffuse, of the normal pancreatic tissue by mature fatty
      tissue. Its definitive diagnosis is made based on histopathologic analysis.
      Nevertheless, typical imaging findings can allow a non-invasive diagnosis and
      help its clinical approach.

PMID- 29332407
TI  - Nutritional deficiency during colonoscopy preparation: the forgotten iatrogeny.
AB  - BACKGROUND AND AIMS: bowel preparation for colonoscopy induces a semi-fasting
      state, with a potential negative impact on fragile patients. The present study
      aims to quantify nutritional deficiency during colonoscopy preparation. METHODS:
      this was an observational and cross-sectional study. A convenience sample was
      obtained that included adults that underwent colonoscopy after bowel preparation
      with Klean-Prep(r) according to the center protocol. Anthropometric evaluation
      was performed and nutritional deficiency was calculated via the quantification of
      energy and protein intake during the 48 hours prior to the examination which was
      compared with the individuals' needs. The association between nutritional
      deficiency with the quality of bowel preparation, age and status
      (hospitalized/ambulatory) was evaluated. RESULTS: the study included 131 patients
      aged 21-91 years (mean 63.6 +/- 13.2 years); 73 cases were male. Malnutrition
      reached 67.2% using specific anthropometric tools. A median preparation quality
      of six points was found when the Boston Bowel Preparation Scale was considered.
      The mean intake 48 hours prior to the procedure was 1,795 kcal and 100 g of
      protein. A daily energy intake of less than 50% of the individual needs was
      observed in 88 patients and less than 25% in 29 cases. The mean energy and
      protein deficiency were 59% (p < 0.01) and 45% (p < 0.01), and there was no
      correlation with preparation quality (p > 0.05). Nutritional defiency is similar
      in hospitalized and ambulatory patients (p > 0.05), but higher in older
      individuals (p = 0.04). CONCLUSIONS: nutritional deficiency during colonoscopy
      preparation was significant, more so in older patients, and there was no
      correlation with the quality of bowel preparation. We conclude that bowel
      preparation regimens should be reformulated with an improved nutritional intake
      and the inclusion of nutritional supplements without residues.

PMID- 29332408
TI  - Effect of induction chemotherapy on the quality-of-life in patients with advanced
      stage tongue cancer by a prospective study.
AB  - Abstracts Objective To assess how induction chemotherapy affects the quality-of
      life (QoL) in patients with advanced tongue cancer. Methods This prospective
      study included patients who were diagnosed with advanced tongue cancer. Each
      patient was asked to complete the University of Washington QoL (UW-QoL), version
      4, questionnaire preoperatively and at 12 months after surgery. Patients were
      divided into two groups based on whether or not they received induction
      chemotherapy. Results Of the 192 patients included in the analysis, 145 patients
      had received induction chemotherapy. There were no significant differences
      regarding age, sex, tumour stage, node stage, flap reconstruction, tumour
      resection range and radiotherapy between the two groups. The mean total hospital
      cost was significantly higher in patients who underwent induction chemotherapy
      compared with those who did not (68 000 versus 44 000 Yuan Renminbi,
      respectively). The two groups had similar pre-treatment and post-treatment
      composite QoL scores and in the 12 individual domains. Conclusion Induction
      chemotherapy had a limited effect on postoperative QoL in patients with advanced
      tongue cancers, but it cost significantly more to administer.

PMID- 29332409
TI  - High-dose ulinastatin improves postoperative oxygenation in patients undergoing
      aortic valve surgery with cardiopulmonary bypass: A retrospective study.
AB  - Objective To determine whether pre-treatment with high-dose ulinastatin provides
      enhanced postoperative oxygenation in patients who have undergone aortic valve
      surgery with moderate hypothermic cardiopulmonary bypass (CPB). Methods Patients
      who underwent aortic valve surgery with moderate hypothermic CPB were
      retrospectively evaluated. In total, 94 of 146 patients were included. The
      patients were classified into one of two groups: patients in whom ulinastatin
      (10,000 U/kg followed by 5,000 U/kg/h) was administered during CPB (Group U, n =
      38) and patients in whom ulinastatin was not administered (Group C, n = 56). The
      PaO2/FiO2 ratio was calculated at the following time points: before CPB (pre
      CPB), 2 h after weaning from CPB (post-CPB), and 6 h after arrival to the
      intensive care unit (ICU-6). The incidence of a low PaO2/FiO2 ratio was also
      compared among the time points. Results Group U showed a significantly higher
      PaO2/FiO2 ratio (F(4, 89.0) = 657.339) and a lower incidence of lung injury
      (PaO2/FiO2 ratio < 300) than Group C at the post-CPB and ICU-6 time points.
      Conclusion High-dose ulinastatin improved pulmonary oxygenation after CPB and in
      the early stages of the ICU stay in patients undergoing aortic valve surgery with
      CPB.

PMID- 29332410
TI  - Myocardial strain/stress changes identified by echocardiography may reveal early
      sepsis-induced myocardial dysfunction.
AB  - Objective To perform early assessment of sepsis-induced myocardial dysfunction
      (SIMD) using strain/stress echocardiography. Methods A canine model of SIMD was
      established using intravenous injection of lipopolysaccharide (LPS, 2 mg/kg).
      Thirteen dogs were included, comprising an LPS-treated SIMD group ( n = 7) and
      saline control group ( n = 6). SIMD was assessed at various time-points using
      cardiac measurements including haemodynamics and echocardiography. Results
      Systolic and radial ventricular wall stress and circular ventricular wall stress
      (WSsc) were significantly lower in the sepsis group versus the control group at
      all time-points. Logistic regression analysis revealed an inverse correlation
      between stress rate of the front-posterior and bottom wall and left ventricle
      systolic wall strength. In contrast, a positive correlation was found between the
      mean velocity of circumferential fibre shortening (mVCF) or heart rate-adjusted
      mVCF (RVCF) and WSsc. Using regression equations, predicted values for mVCF and
      RVCF in animals with sepsis were significantly higher than measured values at 4-
      5- and 6-h time-points. Conclusions These findings will further the understanding
      of pathophysiological alterations in SIMD at the early stage of sepsis, and
      suggest that strain rate may reflect the nature of myocardial contractility.

PMID- 29332412
TI  - [Investigation of the burnout syndrome among the employees of the Department of
      Emergency Medicine at the University of Szeged].
AB  - INTRODUCTION: Burnout has been described as a growing problem amongst healthcare
      workers. Emergency department staffs experience the burden of stress day by day,
      yet only a few studies have examined their burnout. AIM: In this study we wanted
      to investigate the burnout and its relations to other variables amongst the
      employees of the Department of Emergency Medicine in Szeged. METHOD: Cross
      sectional design utilizing a self-administered questionnaire was used to collect
      data from the staff of the Department. Burnout was measured using the Maslach
      Burnout Inventory. RESULTS: Burnout is considerably prevalent among the workers
      of the Emergency Department, especially nurses and physicians. The study found
      negative relation between burnout and age, number of children, number of years in
      the healthcare system, number of physical symptoms, social support and
      psychological immune system. Being single was a risk factor. CONCLUSIONS: The
      risks and protective factors found to be associated with burnout in this study
      might help to set up institutional prevention and intervention strategies. Orv
      Hetil. 2018; 159(3): 113-118.

PMID- 29332411
TI  - beta1 integrin-mediated multicellular resistance in hepatocellular carcinoma
      through activation of the FAK/Akt pathway.
AB  - Objective To explore the role and mechanism of beta1 integrin in the regulation
      of multicellular drug resistance in hepatocellular carcinoma (HCC). Methods This
      in vitro study used a liquid overlay technique to obtain multicellular spheroids
      of two human HCC cell lines, HepG2 and Bel-7402. The morphology of the spheroids
      was observed by optical and electron microscopy. The effects of exposure to 5
      fluorouracil (5-FU) and cisplatin (CDDP) on cell proliferation and the induction
      of apoptosis were assessed in monolayer cells and multicellular spheroids. The
      levels of beta1 integrin and the effects on the focal adhesion kinase
      (FAK)/protein kinase B (Akt) pathway were evaluated using Western blot analysis,
      immunofluorescence and flow cytometry. The role of beta1 integrin was confirmed
      by using an inhibitory antibody. Results Cell proliferation inhibition and cell
      apoptosis induced by 5-FUl and CDDP were abrogated in multicellular spheroids
      compared with monolayer cells. There were high levels of beta1 integrin in
      multicellular spheroids. beta1 integrin inhibitory antibody prevented the
      formation of multicellular spheroids, coupled with a significant increase in
      proliferation inhibition and apoptosis induction. beta1 integrin inhibitory
      antibody effectively suppressed activation of both FAK and Akt in multicellular
      spheroids. Conclusions beta1 integrin mediated multicellular drug resistance
      through the FAK/Akt pathway in HCC spheroids.

PMID- 29332414
TI  - [Interatrial block and its clinical relevance. Renaissance of an ECG change].
AB  - Interatrial block involves conduction delay between the right and left atria
      during sinus rhythm. The review describes the classification, pathomechanism and
      clinical significance of this under-recognised ECG sign, nominated Bayes
      syndrome. The presented ECGs help to recognise the differentypes of interatrial
      blocks. Orv Hetil. 2018; 159(3): 91-95.

PMID- 29332415
TI  - [Prognostic importance of albumin in oncology].
AB  - Diminished serum albumin level can be observed in inflammatory processes. Serum
      albumin level also reduces - irrespective of the presence of malnutrition - in
      locally advanced or metastatic malignancies. Low serum albumin level may have an
      influence also on the results of anticancer therapy (e.g., drug pharmacokinetics,
      adverse drug reactions). Extensive data of the literature and empirical
      experience prove the better prognosis of patients involved in nutritional
      therapy. Based on the most relevent data of the literature, the authors summarize
      the studies which have revealed the close correlation between the baseline serum
      albumin level and the prognosis of malignant diseases. Orv Hetil. 2018; 159(3):
      96-106.

PMID- 29332416
TI  - [Autoimmune encephalitis: possibilities in the laboratory investigation].
AB  - INTRODUCTION: The role of autoimmune responses against central nervous system
      (CNS) antigens in encephalitis presenting with non-classified neurologic or
      psychiatric symptoms has been appreciated in the past decade. Paraneoplastic
      limbic encephalitis has a poor prognosis and is most commonly associated with
      lung, ovarium, and testicular neoplasms, leading to immune reactions against
      intracellular antigens (anti-Hu/ANNA1, anti-Ri/ANNA2, anti-CV2/CRMP5 and anti
      Ma2/Ta). In contrast, the recently described autoimmune encephalitis subtypes
      present with a broad spectrum of symptoms, respond to autoimmune therapies well
      and usually associate with autoantibodies against neuronal cell surface receptors
      (NMDAR, GABABR, AMPAR) or synaptic proteins (LGI1, CASPR2). AIM: Our aim is to
      bring to awareness the increasing number of autoimmune encephalitis patients
      requiring neurologic, psychiatric and intensive care and to emphasize the
      significance of detecting various autoantibodies in diagnosing patients. METHOD:
      In the past 6 years, our laboratory received 836 autoimmune encephalitis
      diagnostic test requests from a total of 717 patients. Serum and cerebrospinal
      fluid (CSF) samples were analysed with indirect immunofluorescence using a
      BIOCHIP consisting of cell lines transfected with 6 different receptor proteins.
      RESULTS: IgG autoantibodies against receptor proteins were present in 7.5% of
      patients. The frequency of positive samples was the following: NMDAR > LGI1 >
      GABABR > CASPR2. CONCLUSION: Detecting autoantibodies facilitates the diagnosis
      of autoimmune encephalitis in an early stage. Patients diagnosed early can be
      effectively treated with plasmapheresis and immunosuppressive drugs. The
      efficiency of therapies can be monitored by autoantibody detection. Therefore,
      the diagnostic immune laboratory plays an important role in proper diagnosis and
      in the prevention of rapidly progressing symptoms. Orv Hetil. 2018; 159(3): 107
      112.

PMID- 29332417
TI  - [Concise history of toxicology - from empiric knowledge to science].
AB  - Toxicology is a science of poisonings by xenobiotics and endogenous physiological
      changes. Its empiric roots may be traced back to the emerging of the human race
      because the most important pledge of our predecessors' survival was the
      differentiation between eatable and poisonous plants and animals. In the course
      of social evolution, there were three main fields of using poisons: 1) hunting
      and warfare, 2) to settle social tensions by avoiding military conflicts through
      hiding strategy of eliminating enemies by toxic substances, 3) medicines applied
      first as anti-poisons and later by introducing strong substances to defeat
      diseases, but paradoxically active euthanasia is also a part of the whole story.
      The industrial revolution of the 19th century changed the sporadic occupational
      diseases to mass conditions. Later the chemical industry and subsequently the
      mass production of synthetic materials turned out as a global environmental
      catastrophe. This latest change initiated the emerging of ecological toxicology
      which is a future history of the concerning ancient science. Orv Hetil. 2018;
      159(3): 83-90.

PMID- 29332419
TI  - Adolescent Stress Treatment Study: A Cluster Randomized Trial.
AB  - High school students experience a variety of stressors. Mental health issues are
      critical to their health. The "Adolescent Stress Treatment (AST) Study: A Cluster
      Randomized Trial" compared the efficacy of two stress reduction devices, the
      EnergyPodTM and the SleepWingTM. The EnergyPodTM is a device that provides a
      semiprivate acoustical and visual environment for rest, stress reduction, and
      sleep. The SleepWingTM is a smaller device offering similar benefits. High school
      students were offered the opportunity to participate in the AST study when they
      exhibited signs of agitation. The students completed the Profile of Mood States
      Short Form (POMS-SF) pre- and postintervention. Total Mood Disturbance (TMD) was
      measured from the POMS-SF and significant improvement postintervention ( p <
      .001), regardless of intervention used. POMS-SF subscales were all significantly
      improved no matter which device was used. All participants in the study
      dramatically improved their mood after being in either therapeutic device.

PMID- 29332418
TI  - The role of PET and MRI in evaluating the feasibility of skin-sparing mastectomy
      following neoadjuvant therapy.
AB  - Objective To investigate the role of positron emission tomography (PET) and
      magnetic resonance imaging (MRI) in evaluating the feasibility of skin-sparing
      mastectomy in patients with locally-advanced breast cancer (LABC) who will
      undergo neoadjuvant chemotherapy (NAC) by evaluating the sensitivity and
      specificity of PET and MRI compared with skin biopsy results before and after NAC
      treatment. Methods Patients with LABC who were treated with NAC between November
      2013 and November 2015 were included in this study. Demographic, clinical,
      radiological and histopathological features of the patients were recorded.
      Results A total of 30 patients were included in the study with a mean age of 52.6
      years (range, 35-70 years). Sensitivity and specificity for detecting skin
      involvement in LABC was 100%/10% (62%/85%) with MRI and 60%/80% (12%/92%) with
      PET before (after) NAC, respectively. When radiological skin involvement was
      assessed in relation to the final histopathological results, the preNAC PET
      results and histopathological skin involvement were not significantly different;
      and there was no difference between postNAC MRI and histopathological skin
      involvement. Conclusions As preNAC PET and postNAC MRI more accurately determined
      skin involvement, it might be possible to use these two radiological evaluation
      methods together to assess patient suitability for skin-sparing mastectomy in
      selected patients.

PMID- 29332420
TI  - Activated Factor 7 Versus 4-Factor Prothrombin Complex Concentrate for Critical
      Bleeding Post-Cardiac Surgery.
AB  - BACKGROUND: Recombinant and plasma-derived factor products, such as activated
      factor seven (rFVIIa) and four-factor prothrombin complex concentrate (4-factor
      PCC), have been used off-label for bleeding after cardiac surgery, but little
      evidence has been published regarding their efficacy and safety. OBJECTIVE: To
      determine whether there is a difference in chest tube output in patients who have
      received 4-factor PCC or rFVIIa for critical postoperative bleeding associated
      with cardiovascular surgery. METHODS: A retrospective chart review was conducted
      utilizing the electronic medical record system at a 657-bed community, tertiary
      care hospital in Nashville, Tennessee. Nonpregnant patients >=18 years of age
      experiencing significant bleeding during cardiac surgery who received either PCC
      or rFVIIa perioperatively or postoperatively between April 2015 through December
      2016 were eligible for inclusion. Patients were excluded if they received 4
      factor PCC or rFVIIa for any indication other than bleeding during cardiac
      surgery or if they received both agents. RESULTS: Data conclude that there is no
      significant difference in chest tube output 24 hours postoperatively between
      patients treated with 4-factor PCC or rFVIIa. There was no difference in
      bleeding, thromboembolic events, or re-exploration between the rFVIIa and 4
      factor PCC groups, but there was a difference in units of fresh frozen plasma
      administered and hospital length of stay. CONCLUSION: 4-Factor PCC may be an
      equally efficacious alternative to rFVIIa for patients experiencing significant
      bleeding during cardiac surgery. There is no difference in chest tube output;
      therefore, there is no difference in bleeding-either at 24 hours postoperatively
      or total.

PMID- 29332421
TI  - Comparison of Two Weight-Based Desmopressin Dosing Strategies for Spontaneous
      Bleeding.
AB  - BACKGROUND: The pharmacokinetics and pharmacodynamics of desmopressin are
      appropriate for adjusted body weight-based dosing, particularly in obese
      patients. OBJECTIVE: The objective of this study was to describe desmopressin
      dosing strategies, with emphasis on hemostatic outcomes among patients without
      preexisting bleeding disorders. METHODS: This was a single-center, retrospective
      cohort study of patients who received intravenous weight-based desmopressin for a
      hemostatic indication. Demographics, comorbidities, treatment setting,
      indication, site of bleeding, and outcomes were collected from the medical
      record. Primary outcomes included need for procedural intervention to achieve
      hemostasis, transfusion requirement, and death. Association between desmopressin
      dose and outcome was evaluated using chi2 or Fischer's exact tests and logistic
      and linear regression models. Multiple regression analysis was conducted to
      identify other predictors of outcome in the data set. RESULTS: A total of 109
      patients were included (n = 26, dose adjustment; n = 83, no dose adjustment).
      Baseline characteristics were well-matched between groups: mean (SD) age of 57.0
      (13.5) years; mean (SD) Charlson Comorbidity Score of 6.5 (2.8); 37% were obese;
      76% were critically ill; 81% were actively bleeding without differences in site
      of bleeding; and crude mortality was 39%. No differences in death, mean units of
      packed red blood cells transfused, or need for procedural hemostasis were
      observed between adjusted weight- and actual weight-based desmopressin dosing.
      CONCLUSIONS: When used adjunctively to blood product transfusion in actively
      bleeding patients, use of adjusted body weight-based desmopressin did not
      negatively affect clinical outcomes. More data are needed to confirm this dosing
      strategy.

PMID- 29332422
TI  - Unexpected Management Behaviors in Adolescents With Type 1 Diabetes Using Sensor
      Augmented Pump Therapy.
AB  - BACKGROUND: Continuous glucose monitoring can improve glycemic outcomes in
      individuals with type 1 diabetes. However, the constant exposure to real-time
      glucose levels can sometimes lead the individual to make some risky choices to
      address the glycemic excursions. Hence, the purpose of this study was to explore
      the aberrant management behaviors of youth with type 1 diabetes on sensor
      augmented pump therapy (SAPT). METHODS: Participants in a clinical trial using
      SAPT on Medtronic MiniMedTM 640G pump who experienced deteriorating glycemic
      control or unexplained hypoglycemia were identified by the health care
      professional. The pump and/or sensor data uploaded to CareLinkTM Therapy
      Management Software were reviewed in these participants. RESULTS:
      Uncharacteristic management behaviors were identified in five adolescent males.
      Continuous exposure to high glucose levels resulted in obsessive behaviors
      displaying a perfectionistic attitude in two participants. Multiple boluses were
      delivered frequently as uneaten carbohydrates in participant 1 while participant
      2 resorted to delivery of extra insulin by cannula fills. In contrast,
      participant 3 chose to remain hyperglycemic to avoid weight gain while
      participant 4 trusted the system and used sensor glucose readings for
      calibrations, with resultant deterioration in glycemic control in both
      participants. On the other hand, participant 5, due to mistrust in the pump
      suspend function, consumed carbohydrates with downward glucose trends with
      rebound hyperglycemia. CONCLUSIONS: Constant exposure to real-time data can lead
      to unsafe management responses in adolescents with the behavior influenced by
      trust or mistrust in the system. Adolescents should be empowered with problem
      solving strategies for safe management.

PMID- 29332423
TI  - First Experiences With a Wearable Multisensor in an Outpatient Glucose Monitoring
      Study, Part I: The Users' View.
AB  - BACKGROUND: Extensive past work showed that noninvasive continuous glucose
      monitoring with a wearable Multisensor device worn on the upper arm provides
      useful information about glucose trends to improve diabetes therapy in controlled
      and semicontrolled conditions. METHODS: To test previous findings also in
      uncontrolled in-clinic and outpatient conditions, a long-term study has been
      conducted to collect Multisensor and reference glucose data in a population of 20
      type 1 diabetes subjects. A total of 1072 study days were collected and a fully
      on-line compatible algorithmic routine linking Multisensor data to glucose
      applied to estimate glucose trends noninvasively. The operation of a digital log
      book, daily semiautomated data transfer and at least 10 daily SMBG values were
      requested from the patient. RESULTS: Results showed that the Multisensor is
      capable of indicating glucose trends. It can do so in 9 out of 10 cases either
      correctly or with one level of discrepancy. This means that in 90% of all cases
      the Multisensor shows the glucose dynamic to rapidly increase or at least
      increase. CONCLUSIONS: The Multisensor and the algorithmic routine used in
      controlled conditions can track glucose trends in all patients, also in
      uncontrolled conditions. Training of the patient proved to be essential. The
      workload imposed on patients was significant and should be reduced in the next
      step with further automation. The feature of glucose trend indication was
      welcomed and very much appreciated by patients; this value creation makes a
      strong case for the justification of wearing a wearable.

PMID- 29332424
TI  - Salivary metabolomics profile of patients with recurrent aphthous ulcer as
      revealed by liquid chromatography-tandem mass spectrometry.
AB  - Objective We compared the salivary nontargeted metabolite profiles between
      patients with recurrent aphthous ulcer (RAU) and healthy individuals to
      investigate the metabolic alterations associated with RAU. Methods Saliva samples
      were collected from 45 patients with RAU and 49 healthy individuals, and the
      salivary metabolites were quantified using liquid chromatography-tandem mass
      spectrometry. The metabolomic profiles were then analyzed using multivariate and
      univariate statistical methods, and enrichment of the metabolites in various
      biological pathways was assessed. Results In total, 206 significant
      differentiating metabolites (Wilcoxon test, false discovery rate [FDR] of <0.05)
      were identified between patients with RAU and healthy individuals. These
      metabolites were implicated in tryptophan metabolism, steroid hormone
      biosynthesis, and other metabolic pathways. Two commonly circulating steroids,
      estrone sulfate and dehydroepiandrosterone sulfate, were significantly lower in
      the saliva of patients with RAU (Wilcoxon test, FDR < 0.05, power > 0.9).
      Principal component analysis and partial least-squares discriminant analysis
      revealed metabolic perturbations involving RAU, and receiver operating
      characteristic curve analysis with several metabolites showed good diagnostic
      ability for RAU. Conclusions The results of this study indicate that patients
      with RAU are characterized by metabolic imbalances. Psychogenic factors,
      endocrinopathies, and immunosuppression may contribute to the onset of RAU.

PMID- 29332425
TI  - Dermatological Manifestations in Patients Undergoing In Vitro Fertilisation: A
      Prospective Study.
AB  - BACKGROUND: Changing sociodemographic patterns with an increase in the age of
      childbirth have affected fertility rates worldwide. With advancing reproductive
      medicine, assisted reproductive techniques (ARTs) are becoming common. While
      dermatological manifestations in normal pregnancies have been well documented,
      there is a paucity of data regarding cutaneous manifestations in patients
      undergoing ART. OBJECTIVES: The objectives of our study were to estimate the
      incidence and types of dermatological manifestations in patients undergoing in
      vitro fertilisation (IVF) and to study their associations with age, type of
      infertility, and outcome of the procedure. METHODS: A prospective cohort of 200
      patients undergoing IVF in a tertiary care centre was observed for occurrence of
      any dermatological manifestations from initiation of the IVF protocol to the
      outcome of the procedure at 3 weeks after embryo transfer. RESULTS:
      Dermatological manifestations were seen in 27% of the study group, with urticaria
      being the most common cutaneous finding seen in 13.5%, followed by acneform
      eruptions (3%). Twenty-six (96.3%) of patients who manifested with urticaria were
      on progesterone. No statistically significant association was found between the
      occurrence of dermatological manifestations and the outcome of IVF, type of
      infertility, history of ART, and ovum donation in our study. Association between
      the age of the patient and the outcome of IVF cycle was statistically
      significant. CONCLUSION: Dermatological manifestations are seen in almost one
      quarter of patients undergoing IVF, with progesterone-induced urticaria being the
      most common. Occurrence of cutaneous manifestations has no significant
      association with the outcome of IVF.

PMID- 29332426
TI  - Effects of multiple sclerosis and medications on menopausal age.
AB  - Objectives We aimed to determine whether multiple sclerosis (MS) and
      methylprednisolone and disease-modifying drugs have an effect on menopausal age.
      Methods A total of 86 patients and 98 healthy subjects were included in this
      study. The natural menopausal age of the patients and healthy subjects were
      compared. The cumulative dosages of methylprednisolone, beta interferons
      (IFNbetas), and glatiramer acetate were calculated. The effects of the Expanded
      Disability Status Scale (EDSS), duration of the disease, and cumulative dosage of
      medications on menopausal age were evaluated. Results The patients' mean
      menopausal age was 45.3 +/- 4.8 years and healthy subjects' menopausal age was
      46.8 +/- 4.3 years, with no significant difference between the two groups. The
      cumulative dosage of methylprednisolone showed an effect on menopausal age. There
      was a significant inverse correlation between menopausal age and dosage of
      IFNbeta-1b, while the disease duration and EDSS score showed no correlation with
      menopausal age. Conclusions We conclude that menopausal age is not affected by
      MS. However, long-term methylprednisolone and IFNbeta-1b treatments may change
      menopausal age in a dose-dependent manner.

PMID- 29332427
TI  - Serum potassium levels and outcomes in critically ill patients in the medical
      intensive care unit.
AB  - Objective To compare the outcomes of patients with and without a mean serum
      potassium (K+) level within the recommended range (3.5-4.5 mEq/L). Methods This
      prospective cohort study involved patients admitted to the medical intensive care
      unit (ICU) of Siriraj Hospital from May 2012 to February 2013. The patients'
      baseline characteristics, Acute Physiology and Chronic Health Evaluation II
      (APACHE II) score, serum K+ level, and hospital outcomes were recorded. Patients
      with a mean K+ level of 3.5 to 4.5 mEq/L and with all individual K+ values of 3.0
      to 5.0 mEq/L were allocated to the normal K+ group. The remaining patients were
      allocated to the abnormal K+ group. Results In total, 160 patients were included.
      Their mean age was 59.3+/-18.3 years, and their mean APACHE II score was 21.8+/
      14.0. The normal K+ group comprised 74 (46.3%) patients. The abnormal K+ group
      had a significantly higher mean APACHE II score, proportion of coronary artery
      disease, and rate of vasopressor treatment. An abnormal serum K+ level was
      associated with significantly higher ICU mortality and incidence of ventricular
      fibrillation. Conclusion Critically ill patients with abnormal K+ levels had a
      higher incidence of ventricular arrhythmia and ICU mortality than patients with
      normal K+ levels.

PMID- 29332428
TI  - The Effectiveness of Preoperative Preparation for Improving Perioperative
      Outcomes in Children and Caregivers.
AB  - Most children experience significant anxiety during the preoperative period.
      Greater preoperative anxiety may be related to a higher incidence of negative
      behaviors. This study aimed to develop a family-centered preoperative preparation
      program and to evaluate the effects of this program on children's preoperative
      emotional behaviors, postoperative behavior, and posthospital behavior, and on
      caregiver anxiety. A prospective, randomized controlled study was conducted. The
      population consisted of children who underwent minor surgery and their
      caregivers. The control group received standard care, and the experimental group
      received standard care plus preoperative preparation, which included a tour, a
      cartoon video depicting a boy's surgical journey, and familiarization with
      medical equipment. Children's emotional behaviors and caregiver anxiety were
      measured at the preoperative visit, in the preoperative holding area, and at
      induction of anesthesia. Postoperative behavior was measured when children were
      in the recovery room, and the researcher also contacted caregivers 2 weeks after
      the surgery to assess the children's behavior at home. A linear mixed-effects
      model results showed that as the surgery approached, the experimental group had
      fewer and more stable preoperative emotional behaviors (least squares means of
      preoperative emotional behaviors from preoperative visit to induction of
      anesthesia = 10.01-10.95). However, the control group exhibited significantly
      increased preoperative emotional behaviors as the surgery approached (least
      squares means of preoperative emotional behaviors from the preoperative visit to
      induction of anesthesia = 7.87-12.23). Family-centered preoperative preparation
      can effectively improve children's negative emotional behaviors from their time
      in the preoperative holding area to the induction of anesthesia.

PMID- 29332429
TI  - Engagement as predictors of performance in a single cohort of undergraduate
      chiropractic students.
AB  - OBJECTIVE: To investigate the potential association of novel academic and
      nonacademic factors with chiropractic student academic performance. METHODS:
      Students enrolled into year 1 of a chiropractic master's degree (MChiro) at our
      college were selected for this study. Data collected included demographics,
      attendance, virtual learning environment use, additional learning needs, previous
      degree qualifications, and summative marks. Differences between students who had
      to take an examination more than once (resit) and nonresit students were explored
      using t test and chi2 analysis. Relationships between attendance and end-of-year
      marks were explored using regression analysis. RESULTS: Male students
      outperformed female students in four of the six units and as the total year
      average. Students who attended <80% of classes were more likely to have a resit
      in one or more units (relative risk [ RR] = 2.6; 95% confidence interval [CI],
      1.4-4.9). Students who performed poorly (<70%) in the semester 1 unit of a course
      on human structure and failed the semester 1 practical assessment of a course on
      clinical management were significantly more likely to have one or more resit
      assessments in semester 2 units ( RR = 3.5 [95% CI, 2.2-5.7]; RR = 3.2 [95% CI,
      2.0-4.9]). Attendance and unit 105 were independent predictors of one or more
      resits at the end-of-year ( R2 = 0.86, p < .001). CONCLUSION: Attendance and
      first semester summative marks were associated with end-of-year performance. As
      such, these markers of performance may be used to flag struggling students in the
      program.

PMID- 29332431
TI  - Validation of the Ceredigion Youth Screening Tool.
AB  - Evidence suggests that only a small minority of youth offenders will continue
      their behaviour in the longer term and largely independent of any interventions
      they may receive (Bateman, 2011; Haines & Case, 2015). Hence, "screening out"
      this larger low-risk cohort could have a positive impact upon the individual
      through a reduction in stigmatisation/labelling and free up resources for higher
      risk clients. This article outlines development of the Ceredigion Youth Screening
      Tool (CYSTEM)-developed and tested to address the two facets of criminality and
      vulnerability-closely aligned to the eight key risk indicators identified in the
      Risk-Needs-Responsivity (R-N-R) literature (Andrews & Bonta, 2010). Initial
      results with two cohorts of 372 young people indicate good convergent and
      discriminative validity in screening out the lowest level referrals, while also
      identifying 90% of potential future offenders. More importantly, CYSTEM is able
      to screen out approximately 35% of the low-risk offenders that are unlikely to
      require formal evaluation and/or intervention. It is suggested that the
      streamlining of this process using CYSTEM reduces demand on staff time and
      decreases the stigmatisation of young people referred for minor offences.
      Potential improvements to the tool and future developments in statistical risk
      prediction are also discussed.

PMID- 29332430
TI  - Effect of creatine phosphate sodium on bispectral index and recovery quality
      during the general anaesthesia emergence period in elderly patients: A
      randomized, double-blind, placebo-controlled trial.
AB  - Objective To evaluate the effect of creatine phosphate sodium on bispectral index
      (BIS) and recovery quality during the general anaesthesia emergence period in
      elderly patients. Methods This randomized, double-blind, placebo-controlled study
      enrolled patients undergoing transabdominal cholecystectomy under general
      anaesthesia. Patients were randomly assigned to receive either creatine phosphate
      sodium (1.0 g/100 ml 0.9% saline; group P) or 100 ml 0.9% saline (group C) over
      30 minutes during surgical incision. The BIS values were recorded at anaesthesia
      induction (T0), skin incision (T1), cutting the gallbladder (T2), suturing the
      peritoneum (T3), skin closure (T4), sputum suction (T5), extubation (T6) and 1
      min (T7), 5 min (T8), 10 min (T9), and 15 min (T10) after extubation. The
      anaesthesia duration, operation time, waking time, extubation time, consciousness
      recovery time, time in the postanaesthesia care unit (PACU), and the Steward
      recovery scores at T7, T8, T9 and T10 were recorded. Results A total of 120
      elderly patients were randomized equally to the two groups. Compared with group
      C, the BIS values were significantly higher in group P at T5, T6, T7 and T8; and
      the Steward recovery scores at T7 and T8 were significantly higher in group P.
      The waking time, extubation time, consciousness recovery time and time in the
      PACU were significantly shorter in group P compared with group C. Conclusion
      Creatine phosphate sodium administered during transabdominal cholecystectomy can
      improve BIS values and recovery following general anaesthesia in elderly
      patients.

PMID- 29332433
TI  - Slippage of Tightrope Button in Syndesmotic Fixation of Weber C Malleolar
      Fractures: A Case Series.
AB  - BACKGROUND: Tightrope fixation is an emerging technique for syndesmotic fixation
      with promising results. However, our case series highlights the slippage of
      Tightrope buttons as a complication of suture button syndesmotic fixation of
      Weber C malleolar fractures using limited contact dynamic compression (LCDCP)
      plates. METHODS: We report a series of cases from our database in which slippage
      of the Tightrope button through the LCDCP holes in Weber C malleolar fractures
      was noted. We measured the medial clear space (MCS), tibiofibular clear space
      (TFCS), and distal tibiofibular overlap (DTFO) and computed the largest change in
      these measurements from the first postoperative follow-up radiographs. Patient
      records were reviewed for persistent symptoms that could be attributed to the
      loss of syndesmotic fixation and stability. RESULTS: Follow-up radiographs of 3
      patients showed a slippage of the Tightrope button through the LCDCP holes. Two
      of the patients reported persistent ankle pain and swelling with prolonged
      activity. The mean increases in MCS and TFCS among these patients were 0.7 (+/
      0.081) mm and 1.5 (+/-0.798) mm, respectively. The mean decrease in DTFO was 2.2
      (+/-0.864) mm. We next highlight 3 patients with Weber C malleolar fractures who
      underwent suture button syndesmotic fixation using double-stacked one-third
      tubular plates instead of the LCDCP. CONCLUSION: This case series reported
      Tightrope button slippage as an early complication of syndesmotic fixation of
      Weber C malleolar fractures. We propose the use of double-stacked one-third
      tubular plates instead of the LCDCP to avoid this complication. LEVEL OF
      EVIDENCE: Level V, expert opinion.

PMID- 29332432
TI  - Spontaneous fetal femoral fracture: a case report and literature review.
AB  - Spontaneous fetal femoral fractures are uncommon in the paediatric setting. The
      major clinical presentations of a spontaneous fetal femoral fracture are femoral
      angulation, shortness of the femur and even a marked fracture line. This case
      report describes a spontaneous fetal femoral fracture of the right femur, which
      was detected by routine ultrasonography during the 19th week of gestation in a 24
      year-old woman. On routine follow-up visits, the angulation of the right femur in
      the fetus gradually improved. A caesarean section was undertaken at 39 weeks +5
      days of gestation and an X-ray was taken on the second day after birth, which
      showed that the fracture had healed and the callus had been absorbed. The lengths
      of the two femurs of the baby were not equal; the right femur was 84 mm, which
      was 11 mm shorter than the left femur. In cases like this, postnatal follow-up is
      essential so that an operation can be carried out in a timely manner when the
      deformity is apparent.

PMID- 29332435
TI  - CHANGES IN THE HEMOCYTE PICTURE OF GALLERIA MELLONELLA (LINNAEUS).
AB  - 1. The hemocytes of Galleria mellonella (Linnaeus) larvae were identified and
      differentially counted in unfixed hemolymph with phase microscopy. The numbers of
      hemocytes per microliter of hemolymph were obtained from both unfixed and heat
      fixed larvae. Hemolymph volumes were determined by the amaranth red method. These
      studies were made to determine what changes in the hematology occur as the last
      stage larvae pass through distinctive phases in transforming into pupae. 2. In
      differential counts, plasmatocytoids decrease, immature adipohemocytes suddenly
      appear, and mature adipohemocytes steadily increase. Spherule cells, oenocytoids
      and dividing hemocytes decrease as Galleria larvae develop into pupae. 3. The
      numbers of hemocytes per microliter of hemolymph increase as Galleria larvae
      proceed towards the pupal stage in both unfixed and heat-fixed animals. Counts
      were always significantly higher in heat-fixed than in unfixed larvae. 4. The
      hemolymph volume is the same in both unfixed and heat-fixed larvae. The hemolymph
      volume declines from about 34% (56.7 microliters) in precocoonspinning larvae to
      less than 16.4% (19 microliters) in newly formed pupae. 5. It is estimated from
      the various data presented that an average of 1,456,000 hemocytes remain in
      circulation within the hemocoele of unfixed larvae from the fifteenth through the
      twentieth days of life, and that with pupation more than one-half of these cells
      fall out of circulation. 6. In three out of 5 cases it was possible to correlate
      decreases in the plasmatocytoid population with increases in adipohemocytes. It
      is suggested that during the spinning of a cocoon plasmatocytoids transform into
      both immature and mature adipohemocytes, that when the larvae are densely
      cocooned mature adipohemocytes are largely formed by the maturation of immature
      adipohemocytes, and that in pharate pupae new mature adipohemocytes are derived
      from both immature adipohemocytes and plasmatocytoids. 7. The hemocyte picture of
      Galleria is compared to that of Prodenia and Bombyx. In all three of these
      Lepidoptera the plasmatocytoids decrease and the hemocytes with many
      polysaccharide and/or lipid or other types of inclusions increase prior to
      pupation. Galleria differs from the other two species in that their hemocytes
      with lipid or other inclusions do not appear until about the sixteenth or
      seventeenth days of larval life, do not divide, and in many cases are derived
      from circulating plasmatocytes.

PMID- 29332434
TI  - Relationship between antimicrobial-resistance programs and antibiotic dispensing
      for upper respiratory tract infection: An analysis of Australian data between
      2004 and 2015.
AB  - Objective NPS MedicineWise aims to ensure that medicines are prescribed and used
      in a manner consistent with current evidence-based best practice. A series of
      nationwide educational and advertising interventions for general practitioners
      and consumers were implemented in Australia between 2009 and 2015 with the aim of
      reducing antibiotic prescriptions for upper respiratory tract infections (URTIs).
      The work described in this paper quantifies the change in antibiotic dispensing
      following these interventions. Methods Antibiotic dispensing data between 2004
      and 2015 were obtained from a national claims database. A Bayesian structural
      time series model was used to forecast a series of antibiotic dispensing volumes
      expected to have occurred if the interventions had not taken place. These were
      compared with the volumes that were actually observed to estimate the
      intervention effect. Results On average, 126,536 fewer antibiotics were dispensed
      each month since the intervention programs began in 2009 (95% Bayesian credible
      interval = 71,580-181,490). This change represents a 14% total reduction in
      dispensed scripts after the series of intervention programs began in 2009.
      Conclusions Continual educational intervention programs that emphasise the
      judicious use of antibiotics may effectively reduce inappropriate prescribing of
      antibiotics for the treatment of URTIs at a national level.

PMID- 29332436
TI  - UTILIZATION OF DISSOLVED EXOGENOUS NUTRIENTS BY THE STARFISHES, ASTERIAS FORBESI
      AND HENRICIA SANGUINOLENTA.
AB  - 1. Small specimens of A. forbesi and H. sanguinolenta were exposed to dissolved
      C14-amino acids and glucose. The subsequent distribution of these materials was
      then determined in the following five regions of the body: disk (including the
      gonads), oral body wall of the rays, aboral body wall of the rays, stomach, and
      digestive glands. 2. In all cases, large proportions of the labeled nutrients
      were taken up into the external tissues. The largest amount was usually absorbed
      into the oral body wall, which probably possesses a proportionately greater
      ventilated surface area than the other regions. 3. Over a period of 20 days there
      was little indication of movement of the externally absorbed nutrients into the
      internal organs. In this period, very little loss of amino acid radioactivity was
      noted. The amino acids became progressively less soluable in alcohol, suggesting
      that they were incorporated into the structural proteins of the organism. 4.
      Glucose radioactivity declined progressively over the 20-day period. As observed
      in Asterias, this decline occurred almost exclusively in the portion of absorbed
      glucose that remained alcohol-soluble. This fraction was possibly used as an
      energy source while the insoluble fraction became incorporated into more inert
      elements. 5. A number of the specimens of Henricia appeared to pump up and absorb
      the glucose medium into their digestive organs. This was interpreted as a form of
      feeding behavior possibly initiated by the relatively high concentration of
      glucose used. The much less concentrated amino acid medium failed to initiate
      such a reaction. 6. It is concluded that nutrition in starfish is probably a dual
      process involving both a continuous epidermal absorption of dissolved exogenous
      materials for the benefit primarily of the superficial tissues, and intermittent
      oral feeding to satisfy the more general needs of the entire organism and
      especially of the internal organs.

PMID- 29332437
TI  - ENVIRONMENTALLY CONTROLLED INDUCTION OF PRIMARY MALE GONOCHORISTS FROM EGGS OF
      THE SELF-FERTILIZING HERMAPHRODITIC FISH, RIVULUS MARMORATUS POEY.
AB  - 1. Rivulus marmoratus is the only known hermaphroditic fish species naturally
      self-fertilizing. Tissue grafts between wild-caught fish and their uniparental
      laboratory descendants give the autograft reaction, indicating propagation by
      selfing in the wild also. Only hermaphrodites have been found in the wild
      locally, although selfing through more than 10 uniparental laboratory generations
      yielded a few primary male gonochorists, under 5% in contrast to over 95% that
      were hermaphrodites. Females seem to be non-existent. 2. Two series of
      experiments were undertaken to identify a possible environmental factor able to
      cause a deviation to the male phenotype during sex differentiation, on the
      working hypothesis that low male incidence in clones composed otherwise of
      hermaphrodites indicated a lability in the sex-determining mechanism through
      which the genotype normally produces the hermaphrodite phenotype. 3. Individuals
      of two clones, each in its own jar throughout life, were exposed to the eight
      combinations of bright or dim light, sea water or fresh water, high or low
      temperature (Experimental Series One). Exposure was from not later than the 3/4
      blastoderm stage until sexual maturity at high temperature or five months post
      hatching at low. 4. Over seven times the number of males previously encountered
      were obtained all but one from low-temperature treatments. Male production was
      correlated with low-temperature rearing despite alternative light intensities and
      salinities and structural-functional abnormalities (prolapsed oviduct, pharyngeal
      hyperplasia, kyphosis) peculiar to different dim-light, salinity-temperature
      combinations, and partly attributable to hormonal derangements. Mortalities were
      high enough to present the formal dilemma of a differential male induction versus
      hermaphrodite mortality at low temperature and vice versa at high, but this
      dilemma was resolved by Experimental Series Two. 5. The Experimental Series One
      fish were monitored daily up to 1,376 days post-hatching, by which time almost
      60% of the hermaphrodites had changed to functional secondary male gonochorists,
      the rest dying or killed as hermaphrodites, some each year. Primary males remain
      unchanged except for senile degeneration. Secondary males arise mostly late in
      laboratory-prolonged life, by involution of the ovarian component of the
      ovotestes with further evolution of the testicular component, the caudal ocellus
      fading or vanishing as they become orange like the primary males. 6. In
      Experimental Series Two, mortalities were low and the structural-functional
      abnormalities were absent. All individuals were kept at the same intermediate
      salinity and light intensity: Group A, at moderate temperature throughout to
      maturity; Group B, at the same temperature through hatching, at low temperature
      the first five months post-hatching, thereafter at the moderate temperature;
      Group C, at the moderate temperature up to stages from optic vesicle formation to
      outset of blood circulation, then at low temperature through eclosion and for
      five months post-eclosion. Group-C embryos being cut from their chorions to
      minimize deaths from hatching failure. 7. The Group-A eggs yielded 100%
      hermaphrodites, the Group-B eggs, 92% hermaphrodites and 8% deaths, the Group-C
      eggs, 72% males, 18% hermaphrodites, and 10% deaths. Exposure to low temperature
      from as late as outset of blood circulation produced males. 8. The uniqueness of
      the present experiments and results, exclusion of alternative explanations,
      significance of the temperature effect per se, and the implications of these
      findings for the interpretation of intersexuality in fishes are discussed at
      length.

PMID- 29332438
TI  - NORTHERN PACIFIC GIGANTIONE (ISOPODA).
AB  - 1. Eight species of Gigantione have now been described. One was from the north
      Atlantic, one from the Indian Ocean, two from the south Pacific, and four from
      the north Pacific. Of these last, G. pratti and G. hawaiiensis are new species.
      The hosts of the different species have all been in separate genera, with the
      exception of those for G. giardi and G. hawaiiensis, both of which were in
      Xantho. 2. Dr. Shiino is carrying out an intensive investigation of epicarids in
      the Japanese archipelago, and the writer is in the process of preparing a
      monograph covering the Epicaridea of the northern Pacific (except for those areas
      and forms near Japan). Therefore, it should be expected that many new species and
      possibly genera will be found in the Pacific as collecting continues.

PMID- 29332439
TI  - THE GROWTH AND ACTIVITY OF THE CORPORA ALLATA IN THE LARVAL FIREBRAT, THERMOBIA
      DOMESTICA (PACKARD) (THYSANURA, LEPISMATIDAE).
AB  - 1. The integument of the firebrat, Thermobia domestica, lacks scales until the
      molt from the third to the fourth larval stage, but retains them in all
      subsequent instars. 2. Implantation experiments confirm earlier findings that the
      scaleless integument of first stage larvae will develop scales prematurely when
      implanted into a molting adult, implying that the formation of scales is
      humorally determined. 3. The number of cells in the corpora allata increases
      progressively throughout the life of the firebrat, and the relationship between
      the number of allatal cells and the weight of the firebrat is expressed by the
      regression: y = 10.61 + 1.94x, where y = the number of cells in each corpus
      allatum and x = the weight of the insect in mg. The regression does not intersect
      the origin. 4. The size of nuclei in the corpus allatum remains constant
      throughout life, but the volume of cytoplasm can alter. The minimal cytoplasmic
      volume coincides with the deposition of the first scale-bearing cuticle. The
      amount of cytoplasm then increases abruptly, the level continuing to rise slowly
      throughout the rest of larval life. A further increase may occur in mated
      females. 5. The juvenile hormone activity of the corpora allata, when assayed on
      pupae of the silkmoth Antheraea polyphemus, correlates with the volume of
      cytoplasm in the gland, and is minimal in the third stage. 6. The activity of the
      corpora allata is influenced by the intake of food, specifically protein. 7.
      Dedifferentiation of the epidermis is prevented by the pattern of growth in the
      corpus allatum, which indicates that the secretory potential of the gland,
      expressed as the volume of allatal cytoplasm per milligram body weight, is
      greater during the first through third instars than at any later stage, and by
      the inactivation of juvenile hormone during the molting cycle.

PMID- 29332440
TI  - SURFACE AREA RESPIRATION DURING THE HATCHING OF ENCYSTED EMBRYOS OF THE BRINE
      SHRIMP, ARTEMIA SALINA.
AB  - Oxygen consumption of Artemia salina was measured during development in 0.5 M
      NaCl at 25 degrees  C. A pattern is seen in which the rate of oxygen consumption
      increases rapidly within the first few hours after hydration, remains constant
      for a time, and then increases rapidly again while most of the embryos are
      emerging. This pattern is dependent upon surface area of the developing embryo.
      During emergence, the surface area of the embryo increases 172% over the surface
      area of the encysted embryo. During the same development period, oxygen uptake
      increases by almost the same factor.

PMID- 29332441
TI  - THE RELATIONSHIP OF TEMPERATURE TO THE LARVAL DEVELOPMENT OF NASSARIUS OBSOLETUS
      (GASTROPODA).
AB  - 1. Development of the embryos of Nassarius obsoletus within egg capsules is
      regulated by sea-water temperature. An increase in the time required between
      spawning and the emergence of veliger larvae is slight between 28 degrees  and 20
      degrees  C., about 0.25 day for each degree decrease in temperature. Between 20
      degrees  and 16.5 degrees  C., the corresponding increase was 2 days per degree
      decrease in temperature. At 11.5 degrees  C., development was not completed and
      larvae did not emerge from their egg capsules after nine weeks. However, a large
      proportion of these embryos survived and developed normally through metamorphosis
      when placed at room temperature. 2. The growth rate of planktonic veliger larvae
      of N. obsoletus was greatest at approximately 25 degrees  C. The lowest
      temperature at which the development to metamorphosis was completed was at 16
      degrees  to 17 degrees  C. There was a 46% inhibition in the growth rate of
      larvae between the optimum temperature and the minimum temperature at which
      development is completed. 3. The larval life of N. obsoletus veligers may be
      divided into two stages. The first of these, the "developmental period," is one
      during which rapid growth and morphological development occur. This is followed
      by the "delay period" characterized by a gradual decrease in growth rate. Reduced
      temperature may influence the rate of growth and consequently the length of the
      "developmental period." The termination of the "developmental period" comes with
      the "creeping-swimming stage." The duration of the "delay period" may be quite
      variable and is determined by the availability of a favorable sediment for
      settlement.

PMID- 29332442
TI  - THE MORPHOLOGY, LIFE-HISTORY, AND SYSTEMATIC RELATIONS OF THE DIGENETIC
      TREMATODE, UNISERIALIS BREVISERIALIS SP. NOV., (NOTOCOTYLIDAE), A PARASITE OF THE
      BURSA FABRICIUS OF BIRDS.
AB  - Imbricata-type cercariae from Hydrobia salsa, a brackish-water, prosobranch snail
      taken near Woods Hole, Massachusetts, emerge shortly before noon, are
      photopositive and encyst after swimming for a few minutes to three to four hours.
      Metacercariae were fed to chicks and domestic ducklings and developed to mature
      worms after about two weeks in the bursae Fabricii of these birds. Adult and
      larval stages are described and figured. The worms belong in the family
      Notocotylidae and are assigned to the genus, Uniserialis Beverley-Burton, 1958.
      Systematic problems of genera in the family are discussed.

PMID- 29332444
TI  - THE EFFECT OF LIGHT ON THE SPAWNING OF CIONA INTESTINALIS.
AB  - 1. The spawning of Ciona intestinalis with respect to light was studied, using
      both white light and monochromatic light. 2. A one-hour dark-adaption period
      followed by exposure to light resulted in spawning by 66.6% of the 884 animals
      tested. 3. Spawning occurs an average of 27.3 minutes after the onset of
      illumination. 4. Illumination need not be continuous until spawning occurs; the
      animals spawn when returned to the dark after a short illumination period,
      provided they have received enough energy. 5. The action spectrum for spawning
      suggests cytochrome c as a chromophore.

PMID- 29332443
TI  - GENETIC AND DEVELOPMENTAL STUDIES ON BOTRYLLUS SCHLOSSERI.
AB  - 1. Properties of Botryllus schlosseri which give it outstanding promise for
      studies in developmental genetics are reviewed. 2. Laboratory culture procedures,
      in vitro fertilization, and a method for raising embryos in vitro are described.
      Controlled successions of complete life cycles can now be achieved in any
      laboratory. 3. Experiments involving colony fusion, subsequent vascular budding,
      and the analysis of color patterns in resultant systems suggest that cells of the
      simple vessel walls govern the morphology of the regenerated zooids. 4. Results
      of some preliminary genetic crosses are reported.

PMID- 29332445
TI  - Stylet angulation of 70 degrees reduces the time to intubation with the
      GlideScope(r): A prospective randomised trial.
AB  - Objective The GlideScope(r) videolaryngoscope provides a good view of the
      glottis. However, directing and inserting an endotracheal tube is sometimes
      difficult during intubation with the GlideScope(r). In this study, we compared
      two GlideScope(r) stylet angulations (90 degrees  vs. 70 degrees ) in terms of
      the time to intubation. Methods In total, 162 patients scheduled for elective
      surgery under general anaesthesia were randomly assigned to one of two groups. In
      the 90 group ( n = 79), a 90 degrees  stylet was used. In the 70 group ( n = 78),
      a 70 degrees  stylet was used. The time to intubation was recorded. The number of
      intubation attempts was assessed. Results The time to intubation was
      significantly shorter in the 70 than 90 group [26.0 (23.0-32.0) vs. 37.0 (30.0
      43.0) s, respectively]. The first-time intubation success rate was significantly
      higher and the number of failed intubations was significantly lower in the 70
      than 90 group (100% vs. 87% and 0% vs. 6%, respectively). Conclusions This
      investigation suggests that a 70 degrees  angle stylet is superior to a 90
      degrees  angle stylet for GlideScope(r) intubation. Trial Registration
      Clinicaltrials.gov Identifier: NCT02547064.

PMID- 29332446
TI  - Lung Cancer Complicated With Asymptomatic Pulmonary Embolism: Clinical Analysis
      of 84 Patients.
AB  - BACKGROUND AND OBJECTIVE: Pulmonary embolism is potentially life-threatening in
      patients with lung cancer, but the clinical studies on patients with lung cancer
      having asymptomatic pulmonary embolism were barely reported. METHODS: Clinical
      data of patients with lung cancer were obtained from the Department of
      Respiratory and Critical Care Medicine of Tianjin Chest Hospital during July 2012
      and June 2015 and were reviewed retrospectively. A total of 28 patients with lung
      cancer having pulmonary embolism (LP group) were enrolled, and another 56 cases
      with lung cancer alone (LC group) were enrolled as controls. RESULTS: Seventeen
      (60.7%) of 28 patients in the LP group developed adenocarcinoma, which was more
      frequent than that in the LC group ( P < .01); the LP group displayed lower
      counts of hemoglobin and albumin than the LC group ( P < .05); the counts of
      leukocyte (white blood cell) and d-dimer of patients in the LP group were also
      higher than those in the LC group ( P < .05). The high-incidence period of
      pulmonary embolism among 17 asymptomatic cases in the LP group was 3.6 months
      postdiagnosis (95% confidence interval, 3.2-4.0), showing a significant
      difference with that of other 11 patients with symptomatic pulmonary embolism,
      which was 10.5 months (95% confidence interval, 8.88-12.12; P < .01). Survival
      analysis displayed that median survival time of patients with asymptomatic
      pulmonary embolism was 7.2 months (95% confidence interval, 5.86-8.56), while
      that of symptomatic pulmonary embolism was 2.8 months (95% confidence interval,
      2.48-3.12). Log-rank examination showed that survival time of asymptomatic
      pulmonary embolism group was statistically longer than that of symptomatic
      pulmonary embolism group. CONCLUSION: Lung adenocarcinoma, chemotherapy,
      hyperleukocytosis, and d-dimer increment were the risk factors for lung cancer
      combined with asymptomatic pulmonary embolism.

PMID- 29332447
TI  - A Projection Quality-Driven Tube Current Modulation Method in Cone-Beam CT for
      IGRT: Proof of Concept.
AB  - PURPOSE: To develop a projection quality-driven tube current modulation method in
      cone-beam computed tomography for image-guided radiotherapy based on the prior
      attenuation information obtained by the planning computed tomography and then
      evaluate its effect on a reduction in the imaging dose. MATERIALS AND METHODS:
      The QCKV-1 phantom with different thicknesses (0-400 mm) of solid water upon it
      was used to simulate different attenuation (MU). Projections were acquired with a
      series of tube current-exposure time product (mAs) settings, and a 2-dimensional
      contrast to noise ratio was analyzed for each projection to create a lookup table
      of mAs versus 2-dimensional contrast to noise ratio, MU. Before a patient
      underwent computed tomography, the maximum attenuation [Formula: see text] within
      the 95% range of each projection angle (theta) was estimated according to the
      planning computed tomography images. Then, a desired 2-dimensional contrast to
      noise ratio value was selected, and the mAs setting at theta was calculated with
      the lookup table of mAs versus 2-dimensional contrast to noise ratio,[Formula:
      see text]. Three-dimensional cone-beam computed tomography images were
      reconstructed using the projections acquired with the selected mAs. The imaging
      dose was evaluated with a polymethyl methacrylate dosimetry phantom in terms of
      volume computed tomography dose index. Image quality was analyzed using a Catphan
      503 phantom with an oval body annulus and a pelvis phantom. RESULTS: For the
      Catphan 503 phantom, the cone-beam computed tomography image obtained by the
      projection quality-driven tube current modulation method had a similar quality to
      that of conventional cone-beam computed tomography . However, the proposed method
      could reduce the imaging dose by 16% to 33% to achieve an equivalent contrast to
      noise ratio value. For the pelvis phantom, the structural similarity index was
      0.992 with a dose reduction of 39.7% for the projection quality-driven tube
      current modulation method. CONCLUSIONS: The proposed method could reduce the
      additional dose to the patient while not degrading the image quality for cone
      beam computed tomography. The projection quality-driven tube current modulation
      method could be especially beneficial to patients who undergo cone-beam computed
      tomography frequently during a treatment course.

PMID- 29332448
TI  - Helical Therapy is Safe for Lung Stereotactic Body Radiation Therapy Despite
      Limitations in Achieving Sharp Dose Gradients.
AB  - PURPOSE: We observed that many of our helical therapy lung stereotactic body
      radiation therapy plans did not meet the Radiation Therapy Oncology Group (RTOG)
      recommended R50% (volume of 50% of the prescription dose/planning target volume),
      which characterizes the steepness of dose fall off. We hypothesized that despite
      not meeting R50%, helical therapy lung stereotactic body radiation therapy plans
      would confer similar local control and minimal side effects as previously
      reported using nonhelical treatment platforms. MATERIALS AND METHODS: We report a
      retrospective review of all consecutive patients treated off-protocol with
      stereotactic body radiation therapy for peripheral lung lesions from 2008 to 2013
      utilizing helical therapy. Seventy-four patients (81 lesions and 79 plans) were
      treated with doses ranging from 48 to 60 Gy in 3 to 5 fractions prescribed to the
      edge of the planning target volume. RESULTS: Forty-eight (61%) plans had major
      deviation from R50%. Only 1 (<1%) plan had a major deviation from the R100%. All
      plans had > 95% planning target volume coverage by prescription dose, 7(8.6%)
      plans with 121% to 133% maximum dose, and lung V20 Gy <10% in 70 (89%) plans.
      With a median follow-up of 4.7 years (95% confidence interval: 4.1-5.3), local
      control for all patients at 1, 2, and 5 years was 94.6%, 83.4%, and 74%,
      respectively. For patients with primary stage I-II lung cancer (n = 46), the 1,
      2, and 5-year local control: 97.2%, 94.2%, and 86.9%; RC: 97.6%, 82.5%, and
      69.5%; and DM: 3%, 16%, and 33.4%, respectively. Patients treated for lung
      metastases (n = 26) had worse local control at 1, 2, and 5 years: 94.4%, 69.3%,
      and 55.5%, respectively. Side effects were rare with 2 (3%) patients reporting
      chest wall pain and 6 (8%) patients experiencing radiation pneumonitis, including
      1 patient who had grade 5 radiation pneumonitis. CONCLUSIONS: Helical therapy
      delivers a safe and effective lung stereotactic body radiation therapy plan,
      despite not being able to meet RTOG's recommended R50 conformality constraint.

PMID- 29332449
TI  - Mir-452-3p: A Potential Tumor Promoter That Targets the CPEB3/EGFR Axis in Human
      Hepatocellular Carcinoma.
AB  - PURPOSE: We proposed to investigate the effects of miR-452-3p on the
      proliferation and mobility of hepatocellular carcinoma (HCC) cells by targeting
      cytoplasmic polyadenylation element binding protein 3/estimated glomerular
      filtration rate (CPEB3/EGFR) axis. METHODS: Quantitative real-time polymerase
      chain reaction (qRT-PCR) was used to detect miR-452-3p expression in 84 pairs of
      HCC tissues and adjacent tissues. Luciferase reporter assay was employed to
      examine the relationship between miR-452-3p and CPEB3. Microculture tetrazolium
      (MTT) assay, colony formation assay, flow cytometry detection, wound healing
      assay, and transwell assay were used to detect cell proliferation, cycle arrest,
      apoptosis, and mobility, respectively, in HCC, HepG2, and Huh-7. Western blot was
      used to detect protein expression levels in EGFR signaling pathway. Kaplan-Meier
      survival analysis was conducted to analyze the correlation between the miR-452-3p
      and CPEB3 expression levels and the survival of patients with HCC. RESULTS: MiRNA
      452-3p was found significantly upregulated in 84 human HCC sample tissues and
      cells in comparison with adjacent tissues and normal liver epithelial cells ( P <
      .01). Luciferase reporter assay demonstrated that CPEB3 was a direct target of
      miR-452-3p. Overexpression of miR-452-3p promoted cell proliferation and mobility
      and suppressed apoptosis. MiR-452-3p enhanced EGFR and phosphorylated AKT (pAKT)
      expression but inhibited p21 expression level. CONCLUSION: MiR-452-3p promoted
      HCC cell proliferation and mobility by directly targeting the CPEB3/EGFR axis.

PMID- 29332451
TI  - PSCA rs1045531 Polymorphism and the Risk of Prostate Cancer in a Chinese
      Population Undergoing Prostate Biopsy.
AB  - BACKGROUND AND PURPOSE: This study explored the association between a single
      nucleotide polymorphism of prostate stem cell antigen and prostate cancer in
      Chinese patients undergoing prostate biopsy. MATERIALS AND METHODS: DNA from 416
      patients undergoing prostate biopsy was typed for the prostate stem cell antigen
      rs1045531 single-nucleotide polymorphism. The frequency of the rs1045531
      polymorphism in patients with prostate cancer and in patients with benign
      prostatic hyperplasia was compared. Associations between the polymorphism and the
      risk of prostate cancer, prostate special antigen, Gleason score, and clinical
      stage were analyzed. RESULTS: Statistically significant differences in the
      distribution of the rs1045531 genotypes and alleles were found between prostate
      cancer and benign prostatic hyperplasia in patients undergoing prostate biopsy (
      P = .035 and .046, respectively). We found that the rs1045531 AC genotype was
      significantly associated with a high risk of prostate cancer in the heterozygote
      model (AC vs CC; odds ratio = 2.383, 95% confidence interval: 1.198-4.741, chi2 =
      6.229, P = .013) and the dominant model (AA/AC vs CC; odds ratio = 2.169, 95%
      confidence interval: 1.112-4.229, chi2 = 5.228, P = .022). However,
      susceptibility of prostate cancer was decreased in the homozygote model (AA vs
      CC; odds ratio = 0.828, 95% confidence interval: 0.143-4.805, P = .601). When
      considering clinical factors, the rs1045531 showed an association with prostate
      special antigen of 10 ng/mL or greater, a Gleason score of 7 or greater, and a
      size of T2 or greater. CONCLUSION: Men with the rs1045531 AC genotype of prostate
      stem cell antigen were at higher risk of prostate cancer in Chinese patients
      undergoing prostate biopsy.

PMID- 29332452
TI  - The DNMT3B -579G>T Polymorphism Is Significantly Associated With the Risk of
      Gastric Cancer but not Lung Cancer in Chinese Population.
AB  - The -149C>T and -579G>T, 2 single nucleotide polymorphisms in de novo
      methyltransferase 3B gene promoter, have been previously reported to potentially
      alter the promoter activity and to influence cancer risk. However, the results
      from previous studies remain conflicting rather than conclusive. In view of this,
      we conducted a case-control study and then a meta-analysis to examine the
      association between these 2 single-nucleotide polymorphisms with risk of lung and
      gastric cancer in Chinese population. The genotyping was performed by polymerase
      chain reaction-restriction fragment length polymorphism and confirmed by
      sequencing. In this case-control study, no significant association with lung or
      gastric cancer risk was observed for -149C>T, while -579G>T was significantly
      correlated with the risk of gastric cancer but not lung cancer. Moreover,
      haplotype analysis showed that haplotype -149T/-579 T, which carried the risk 
      579 T allele, significantly increased the susceptibility to gastric cancer.
      However, none of the haplotypes was associated with the risk of lung cancer. The
      following meta-analysis involved only Chinese population and further confirmed
      the significant association of -579G>T with gastric cancer but not lung cancer
      and suggested no significant association between -149C>T and risk of lung or
      gastric cancer. Collectively, DNMT3B -579G>T polymorphism is associated with
      gastric cancer risk in Chinese population, and the -579G>T may be used as a
      genetic biomarker to predict the risk of gastric cancer in Chinese population.

PMID- 29332450
TI  - Identification and Comparison of Differentiation-Related Proteins in
      Hepatocellular Carcinoma Tissues by Proteomics.
AB  - Histological differentiation is a major pathological criterion indicating the
      risk of tumor invasion and metastasis in patients with hepatocellular carcinoma.
      The degree of tumor differentiation is controlled by a complex interacting
      network of associated proteins. The principal aim of the present study is to
      identify the possible differentiation-related proteins which may be used for
      early diagnosis and more effective therapies. We compared poorly differentiated
      and well-differentiated hepatocellular carcinoma tissues by using 2-dimensional
      gel electrophoresis and matrix-assisted laser desorption ionization time-of
      flight mass spectrometry. Among the 11 identified protein spots, 6 were found to
      be upregulated in poorly differentiated hepatocellular carcinoma tissues and 5
      were correspondingly downregulated. Immunohistochemistry was performed on 106
      hepatocellular carcinoma tissues to confirm the results of the proteomic
      analysis. By using bioinformatic tools GO and STRING, these proteins were found
      to be related to catalytic activity, binding, and antioxidant activity. In
      particular, our data suggest that overexpression of peroxiredoxin-2, annexin A2,
      and heat shock protein beta-1 was correlated with tumor invasion, metastasis, and
      poor prognosis, and therefore, these proteins may serve as potential diagnostic
      and therapeutic biomarkers.

PMID- 29332454
TI  - Intrafractional Tracking Accuracy of a Transperineal Ultrasound Image Guidance
      System for Prostate Radiotherapy.
AB  - PURPOSE: The aim of this study is to evaluate the tracking accuracy of a
      commercial ultrasound system under relevant treatment conditions and demonstrate
      its clinical utility for detecting significant treatment deviations arising from
      inadvertent intrafractional target motion. METHODS: A multimodality male pelvic
      phantom was used to simulate prostate image-guided radiotherapy with the system
      under evaluation. Target motion was simulated by placing the phantom on a motion
      platform. The tracking accuracy of the ultrasound system was evaluated using an
      independent optical tracking system under the conditions of beam-on, beam-off,
      poor image quality with an acoustic shadow introduced, and different phantom
      motion cycles. The time delay between the ultrasound-detected and actual phantom
      motion was investigated. A clinical case example of prostate treatment is
      presented as a demonstration of the utility of the system in practice. RESULTS:
      Time delay between the motion phantom and ultrasound tracking system is 223 +/-
      45.2 milliseconds including video and optical tracking system frame rates. The
      tracking accuracy and precision were better with a longer period. The precision
      of ultrasound tracking performance in the axial (superior-inferior) direction was
      better than that in the lateral (left-right) direction (root mean square errors
      are 0.18 and 0.25 mm, respectively). The accuracy of ultrasound tracking
      performance in the lateral direction was better than that in the axial direction
      (the mean position errors are 0.23 and 0.45 mm, respectively). Interference by
      radiation and image quality do not affect tracking ability significantly.
      Further, utilizing the tracking system as part of a clinical study for prostate
      treatment further verified the accuracy and clinical appropriateness.
      CONCLUSIONS: It is feasible to use transperineal ultrasound daily to monitor
      prostate motion during treatment. Our results verify the accuracy and precision
      of an ultrasound system under typical external beam treatment conditions and
      further demonstrate that the tracking system was able to identify important
      prostate shifts in a clinical case.

PMID- 29332453
TI  - MRI-Related Geometric Distortions in Stereotactic Radiotherapy Treatment
      Planning: Evaluation and Dosimetric Impact.
AB  - In view of their superior soft tissue contrast compared to computed tomography,
      magnetic resonance images are commonly involved in stereotactic
      radiosurgery/radiotherapy applications for target delineation purposes. It is
      known, however, that magnetic resonance images are geometrically distorted, thus
      deteriorating dose delivery accuracy. The present work focuses on the assessment
      of geometric distortion inherent in magnetic resonance images used in
      stereotactic radiosurgery/radiotherapy treatment planning and attempts to
      quantitively evaluate the consequent impact on dose delivery. The geometric
      distortions for 3 clinical magnetic resonance protocols (at both 1.5 and 3.0 T)
      used for stereotactic radiosurgery/radiotherapy treatment planning were evaluated
      using a recently proposed phantom and methodology. Areas of increased distortion
      were identified at the edges of the imaged volume which was comparable to a brain
      scan. Although mean absolute distortion did not exceed 0.5 mm on any spatial
      axis, maximum detected control point disposition reached 2 mm. In an effort to
      establish what could be considered as acceptable geometric uncertainty, highly
      conformal plans were utilized to irradiate targets of different diameters (5-50
      mm). The targets were mispositioned by 0.5 up to 3 mm, and dose-volume histograms
      and plan quality indices clinically used for plan evaluation and acceptance were
      derived and used to investigate the effect of geometrical uncertainty
      (distortion) on dose delivery accuracy and plan quality. The latter was found to
      be strongly dependent on target size. For targets less than 20 mm in diameter, a
      spatial disposition of the order of 1 mm could significantly affect (>5%) plan
      acceptance/quality indices. For targets with diameter greater than 2 cm, the
      corresponding disposition was found greater than 1.5 mm. Overall results of this
      work suggest that efficacy of stereotactic radiosurgery/radiotherapy applications
      could be compromised in case of very small targets lying distant from the
      scanner's isocenter (eg, the periphery of the brain).

PMID- 29332457
TI  - REPAIR AND REATTACHMENT IN THE BALANIDAE AS RELATED TO THEIR CEMENTING MECHANISM.
AB  - Barnacles, which become partially or totally detached from their substratum in a
      natural environment, produce a secondary cement secretion. Laboratory experiments
      demonstrate that the secondary cement can successfully reattach the barnacle to a
      new substratum. Similar secondary secretion was found at the site of minor
      injuries to the barnacle basis. The secondary cement usually has a looser, more
      cavernous structure than the primary cement, but both secretions have similar
      staining characteristics. Microscope preparations indicate that occasionally
      barnacles are capable of developing new secondary cement ducts leading into the
      injured or detached areas to secrete secondary cement. In most cases, however,
      the existing primary cement duct network is used for the secondary secretion.
      This is possible only because most of the once used ducts are not plugged by
      hardened cement, in spite of the fact that the cement can harden inside the
      ducts. Chemical analysis suggests that the cement is an organic biopolymer and
      indications are that the cement hardening is initiated inside the organism. A
      unique flushing mechanism seems to be responsible for keeping the cement ducts
      open and ready for reuse. A nonhardening flushing fluid forces the still liquid
      cement out of the ducts. The cement hardens outside the duct openings sealing the
      flushing fluid inside the duct network. In case of detachment or injury. the
      cement seal breaks; the flushing fluid drains out leaving the duct open for the
      secondary cement secretion. The vesicles in conjunction with the main channel
      control the flow of the flushing fluid and the cement. The permeable wall of the
      main channel portion inside the vesicle reduces the convection and diffusion
      between the vesicle and the main channel, thus bypassing of vesicles and duct
      networks not affected by detachment is possible. The wall of the main channel
      inside the vesicle is also collapsible, thus acting as checkvalve when the
      vesicle is under pressure and allowing the cement to be pumped only into the
      ducts toward the secretory orifices.

PMID- 29332459
TI  - ABSTRACTS OF PAPERS PRESENTED AT THE MARINE BIOLOGICAL LABORATORY 1970.

PMID- 29332458
TI  - THE APPARENT WATER-PERMEABILITY OF CARCINUS MAENAS (CRUSTACEA, BRACHYURA,
      PORTUNIDAE) AS A FUNCTION OF SALINITY.
AB  - 1. The apparent water-permeability of Carcinus maenas, as measured by D2O influx,
      is 2-3 times higher than that of the more euryhaline crab Rhithropanopeus. 2.
      Like Rhithropanopeus, Carcinus shows a reduction of water-exchange rate at lower
      salinities. The highest hourly water-exchange fraction is in 75% SW (K = 2.73),
      the lowest in 30% SW (K = 1.76); values refer to a crab with wet weight of 10 g,
      at 18 degrees  C. 3. The calculated net diffusional (osmotic) water influx is
      adequate to account for the urine production of Carcinus in 50-70% SW, but does
      not account for urine production in SW, and only inadequately for the urine
      produced in 30-40% SW, and it seems necessary to postulate some isotonic
      transport of water.

PMID- 29332456
TI  - The Combined Antitumor Effects of 125I Radioactive Particle Implantation and
      Cytokine-Induced Killer Cell Therapy on Xenograft Hepatocellular Carcinoma in a
      Mouse Model.
AB  - The combination of radiotherapy and immunotherapy has shown great promise in
      eradicating tumors. For example, 125I radioactive particle implantation and
      cytokine-induced killer cell therapies have demonstrated efficacy in treating
      hepatocellular carcinoma. However, the mechanism of this combination therapy
      remains unknown. In this study, we utilized cytokine-induced killer cells
      obtained from human peripheral blood mononuclear cells along with 125I
      radioactive particle implantation to treat subcutaneous hepatocellular carcinoma
      xenograft tumors in BALB/c nude mice. The effects of combination therapy on tumor
      growth, tumor cell apoptosis and proliferation, animal survival, and immune
      indexes were then assessed. The results indicated that 125I radioactive particle
      implantation combined with cytokine-induced killer cells shows a much greater
      antitumor therapeutic effect than either of the therapies alone when compared to
      control treatments. Mice treated with a combination of radiotherapy and
      immunotherapy displayed significantly reduced tumor growth. 125I radioactive
      particle implantation upregulated the expression of major histocompatibility
      complex (MHC) class I chain-related gene A in hepatocellular carcinoma cells and
      enhanced cytokine-induced killer cell-mediated apoptosis through activation of
      caspase-3. Furthermore, cytokine-induced killer cells supplied immune substrates
      to induce a strong immune response after 125I radioactive particle implantation
      therapy. In conclusion, 125I radioactive particle implantation combined with
      cytokine-induced killer cell therapy significantly inhibits the growth of human
      hepatocellular carcinoma cells in vivo and improves animal survival times through
      mutual promotion of antitumor immunity, presenting a promising therapy for
      hepatocellular carcinoma.

PMID- 29332461
TI  - FILTRATION OF PARTICLES FROM SUSPENSION BY THE AMERICAN OYSTER CRASSOSTREA
      VIRGINICA.
AB  - 1. Particle filtration by the oyster Crassostrea virginica was studied in the 1.0
      to 12.0 u size range in relation to naturally occurring particles and to
      kaolinite suspensions in filtered river water. 2. Oysters were held in troughs of
      flowing water under conditions similar to their natural environment. Particle
      number and volumes entering and leaving the troughs were enumerated using a
      Coulter electronic particle counter. Particle diameter was expressed as that of a
      sphere having a volume equal to the particle. 3. Results of the study were
      expressed as per cent of total particles removed in various size increments or in
      volumes removed over the same size range. 4. Oysters filtered naturally occurring
      particles in the 1.0 to 3.0 u range with about one-third the efficiency as larger
      particles. Above 3.0 u there was no change in efficiency with increasing particle
      size. For kaolinite particles, oysters removed particles in the 1.0 to 2.0 u
      range with about half the efficiency as larger particles. Above this size there
      was no change. 5. When results are expressed in terms of per cent removal, the
      importance of the small sized particles is minimized. In terms of volume,
      particles in the 1.0 to 3.0 u range constitute the largest single size fraction
      over the 1.0 to 12.0 u range. 6. The consistent presence of an inflection point
      at a particle size around 2.0- 3.0 u in the curve for per cent removed vs.
      particle size is an indication that the distance between adjacent latero-frontal
      cilia is the factor that determines the smallest particle size that can be
      completely retained by the oyster gill. 7. Presence of the inflection point is
      also interpreted as negating the existence of a mucous sheet over the gills, as
      suggested by MacGinitie (1941). 8. Particles in the 1.0 to 3.0 u range may play
      an important role in the nutrition of oysters and other lamellibranchs. Their
      removal by these organisms may also be an important factor in sedimentary
      processes.

PMID- 29332455
TI  - DNA Repair Mechanism Gene, XRCC1A ( Arg194Trp) but not XRCC3 ( Thr241Met)
      Polymorphism Increased the Risk of Breast Cancer in Premenopausal Females: A Case
      Control Study in Northeastern Region of India.
AB  - X-ray repair cross complementary group gene is one of the most studied candidate
      gene involved in different types of cancers. Studies have shown that X-ray repair
      cross complementary genes are significantly associated with increased risk of
      breast cancer in females. Moreover, studies have revealed that X-ray repair cross
      complementary gene polymorphism significantly varies between and within different
      ethnic groups globally. The present case-control study was aimed to investigate
      the association of X-ray repair cross complementary 1A (Arg194Trp) and X-ray
      repair cross complementary 3 (Thr241Met) polymorphism with the risk of breast
      cancer in females from northeastern region of India. The present case-control
      study includes histopathologically confirmed and newly diagnosed 464 cases with
      breast cancer and 534 apparently healthy neighborhood community controls.
      Information on sociodemographic factors and putative risk factors were collected
      from each study participant by conducting face-to-face interviews. Genotyping of
      X-ray repair cross complementary 1A (Arg194Trp) and X-ray repair cross
      complementary 3 (Thr241Met) was carried out by polymerase chain reaction
      restriction fragment length polymorphism. For statistical analysis, both
      univariate and multivariate logistic regression analyses were performed. We also
      performed stratified analysis to find out the association of X-ray repair cross
      complementary genes with the risk of breast cancer stratified based on menstrual
      status. This study revealed that tryptophan allele (R/W-W/W genotype) in X-ray
      repair cross complementary 1A (Arg194Trp) gene significantly increased the risk
      of breast cancer (adjusted odds ratio = 1.44, 95% confidence interval = 1.06
      1.97, P < .05 for R/W-W/W genotype). Moreover, it was found that tryptophan
      allele (W/W genotype) at codon 194 of X-ray repair cross complementary 1A
      (Arg194Trp) gene significantly increased the risk of breast cancer in
      premenopausal females (crude odds ratio = 1.66, 95% confidence interval = 1.11
      2.46, P < .05 for R/W-W/W genotype). The present study did not reveal any
      significant association of X-ray repair cross complementary 3 (Thr241Met)
      polymorphism with the risk of breast cancer. The present study has explored that
      X-ray repair cross complementary 1A (Arg194Trp) gene polymorphism is
      significantly associated with the increased risk of breast cancer in
      premenopausal females from northeastern region of India which may be beneficial
      for prognostic purposes.

PMID- 29332460
TI  - ACETYLCHOLINESTERASE ACTIVITY IN ESERINE-TREATED ASCIDIAN EMBRYOS.
AB  - 1. The use of specific cholinesterase inhibitors and substrates demonstrated that
      the enzyme activity in Ciona intestinalis larvae is an acetylcholinesterase. 2.
      Eggs treated with eserine sulfate (an acetylcholinesterase inhibitor) for one
      hour prior to fertilization developed into larvae with defective muscular
      movements and greatly reduced levels of acetylcholinesterase activity. 3. Two
      kinds of experiments show that this reduced enzyme activity was caused by the
      retention of eserine and not by inhibition of acetylcholinesterase synthesis.
      Homogenates of embryos from eserine-treated eggs inhibit acetylcholinesterase
      activity when mixed with homogenates of control embryos. Full enzyme activity in
      homogenates of the experimental embryos could be recovered by dialysis.

PMID- 29332462
TI  - STUDIES ON THE BIOLUMINESCENCE OF THE MARINE OSTRACOD CRUSTACEAN CYPRIDINA
      SERRATA.
AB  - 1. The physical appearance and bioluminescence behavior, and light-emitting
      reaction of the marine ostracod crustacean, Cypridina serrata, are described. 2.
      In the natural environment of the sea, the free-swimming C. serrata appears to
      emit almost instantaneously a bright blue luminous cloud when stimulated with
      artificial light. 3. The method of light production, consisting of the ejection
      of luciferin and luciferase into sea water, and the color of light are similar to
      that of C. hilgendorfii. 4. In captivity, C. serrata emits apparent spontaneous
      flashes of light, whose duration is approximately 1.5 seconds, with an apparent
      latency of 500-800 milliseconds. 5. C. serrata luciferase cannot be distinguished
      from C. hilgendorfii luciferase by gel elution chromatography but may be
      distinguished immunochemically. 6. The luminescence of C. serrata is due to a
      first order reaction, similar to that of C. hilgendorfii. The luciferins and
      luciferases of both organisms cross-react to give light. 7. The luminescence of
      C. serrata, like C. hilgendorfii, is oxygen dependent. 8. C. serrata luciferin is
      similar, if not identical, to C. hilgendorfii luciferin when compared by paper
      chromatography.

PMID- 29332463
TI  - CHANGES IN MICROTUBULES OF CILIA AND FLAGELLA FOLLOWING NEGATIVE STAINING WITH
      PHOSPHOTUNGSTIC ACID.
AB  - 1. Variability in the macerating action of 1% aqueous phosphotungstic acid, pH
      6.8, is exemplified in microtubules of flatworm and rhynchocoel cilia, from one
      grid square to another of the same preparation and within a single grid square.
      The central singlets appear to be the most susceptible and are often completely
      absent, even in cases where the binding matrix is still present around the
      doublets. Maceration usually, but not always, begins at the distal tip of a
      cilium and proceeds towards the basal plate; it is evident along the lengths of
      doublets as partial or complete loss of one subtubule, as breaks and bends, and
      as fraying into the component protofibrils, with disappearance of the white line
      marking the wall between the subtubules. 2. Cortical singlet microtubules of a
      spermatozoon were thrown into a helical configuration by the action of PTA, while
      the flagellar microtubules of the same spermatozoon were unaffected. 3. After
      treatment with 1% PTA at pH 8.3, the central singlets of cilia (but not the
      doublets) were semi-fused along most of their lengths, and had a beaded
      appearance; there were breaks in the doublets but otherwise they appeared to be
      unaffected. 4. Ciliary rootlets were rarely seen, but when present had a clear
      790 A major repeating pattern and a longitudinal fibrous substructure.

PMID- 29332464
TI  - THE ORIGIN, DISTRIBUTION AND FATE OF THE MOLTING FLUID PROTEINS OF THE CECROPIA
      SILKWORM.
AB  - 1. Molting in insects is always accompanied by the production of a molting fluid
      which fills the exuvial space between the new and the old cuticle and digests the
      inner layers of the old cuticle. In Hyalophora cecropia, molting fluid is
      secreted at the outset of adult development and persists until two days before
      eclosion, whereupon it is absorbed. 2. The present report examines the protein
      composition of the molting fluid of Cecropia, the origin of the molting fluid
      proteins, the relation of these proteins to blood proteins and the exchange of
      macromolecules between the molting fluid and the blood. It also examines the
      sites of absorption of molting fluid. 3. Disc electrophoresis on acrylamide gels
      reveals that the molting fluid of Cecropia contains about fifteen protein bands
      which can be resolved at pH 8.6. Some of these protein bands are detected in the
      molting fluid at all stages, whereas others appear only at specific times. About
      ten of the bands are peculiar to molting fluid and are not detected in the blood.
      About five bands are detectable in both blood and molting fluid, but none of
      these common bands appears to be a major component of the molting fluid, and only
      one is a major blood protein. In contrast, the epidermis contains most of the
      major protein bands found in molting fluid but lacks all but one of the major
      protein bands present in the blood. 4. Immunological analysis reveals that blood
      and molting fluid share five antigens. At least four of these common antigens
      also occur in the epidermis which appears to secrete these antigens into both the
      molting fluid and the blood. 5. Native and foreign proteins do not penetrate from
      the exuvial space into the blood or vice versa. Apparently the epidermis and
      cuticle act as a barrier to the exchange of most macromolecules between the blood
      and molting fluid. The exuvial space is clearly a separate fluid compartment. 6.
      In addition the exuvial space itself is compartmentalized and the fluids in the
      compartments do not admix several days before eclosion. 7. Absorption of molting
      fluid during the final two days of adult development occurs most readily through
      particular regions of the integument. In the abdomen the principal sites of
      absorption are pits which represent the points through which tonofibrils make
      attachment to the old cuticle. Two days before ecdysis, the attachments between
      the tonofibrils and the pupal cuticle rupture, exposing the points of attachment
      on the new cuticle. It is through these exposed surfaces that much of the molting
      fluid is absorbed. Molting fluid is also absorbed in the head and thorax through
      various flexible membranes at the bases of the appendages.

PMID- 29332465
TI  - CHANGES IN THE EPIDERMAL HISTOLOGY DURING THE SLOUGHING CYCLE IN THE RAT SNAKE
      PTYAS KORROS SCHLEGEL, WITH CORRELATED OBSERVATIONS ON THE THYROID GLAND.
AB  - 1. Study of the epidermal histology throughout the sloughing cycle in the snake
      Ptyas korros revealed the existence of a well-defined mesos layer and showed that
      the alpha-layer is completed in the immediate post-shedding resting-phase. These
      observations supplement previous histological studies of the snake epidermis and
      further substantiate the essential homology of the epidermal generation in these
      forms with similar units in lizards. 2. Thyroid weight is not correlated with
      follicular cell height nor with epidermal cell changes throughout the sloughing
      cycle. 3. Changes in follicular cell height, indicative of varying levels of
      gland activity can be correlated with epidermal changes. The shedding complex and
      the outermost portions of the new inner epidermal generation differentiate during
      a period of lowest thyroid gland activity: gland activity is highest around
      sloughing. 4. These results provide a possible explanation for previous
      experimental studies of thyroid-sloughing relations in snakes. The problem of the
      difference between snakes and lizards in this context is discussed.

PMID- 29332466
TI  - A GENERAL METHOD FOR THE MONOXENIC CULTIVATION OF THE DAPHNIDAE.
AB  - Fourteen species of the family Daphnidae have been established under continuous
      monoxenic cultivation utilizing Chlamydomonas reinhardii as sole food organism in
      a medium consisting of calcium acetate, antibiotics, albumin, trace elements and
      the water soluble vitamins, folic acid, B12, calcium pantothenate, choline,
      pyridoxal, inositol, thiamin, nicotinamide, riboflavin, biotin and putrescine.
      The Daphnidae under cultivation include Daphnia magna, D. pulex, D. galeata
      mendotae, D. laevis, D. dubia, D. retrocurva, D. parvula, D. ambigua, D. catawba,
      Moina macrocopa Scapholeberis mucronata, Simocephalus serrulatus, Ceriodaphnia
      reticulata, and C. quadrangula. The requirements for vitamins for some species
      are more complex than for others. The complete medium is superior for all but
      Scapholeberis mucronata and markedly increases the lifespan and fertility of
      Moina macrocopa.

PMID- 29332467
TI  - Is Hippocampal Avoidance During Whole-Brain Radiotherapy Risky for Patients With
      Small-Cell Lung Cancer? Hippocampal Metastasis Rate and Associated Risk Factors.
AB  - OBJECTIVES: Hippocampal avoidance during whole-brain radiotherapy is performed to
      prevent neural stem cell injury causing neurocognitive dysfunction. Nevertheless,
      the estimated risk of metastases in hippocampal avoidance area in small-cell lung
      cancer is unknown. The current study aimed to characterize the metastatic
      distribution within the brain relative to the hippocampus, estimate the incidence
      of hippocampal metastasis in patients with small-cell lung cancer, and identify
      clinical and radiographic variables that may be associated with the risk of
      hippocampal avoidance area metastasis. MATERIALS AND METHODS: Patients with small
      cell lung cancer treated with therapeutic whole-brain radiotherapy between
      January 2010 and December 2015 were reviewed. T1-weighted, postcontrast axial
      magnetic resonance images obtained just before therapeutic cranial irradiation
      were retrieved and reviewed for each patient. The hippocampal avoidance area was
      defined as hippocampus and 5-mm ring area adjacent to the hippocampus to account
      for necessary dose falloff between the hippocampus and the whole-brain planning
      target volume. Metastatic lesions within hippocampal avoidance area were defined
      as hippocampal metastasis. Hippocampal metastasis rate and characteristics of
      patients with hippocampal metastasis were analyzed and compared to patients
      without hippocampal metastasis. RESULTS: Fifty-four patients evaluated with
      cranial magnetic resonance imaging were enrolled. Hippocampal metastasis rate was
      32% (17 patients). A total of 4.4% of all metastases involved the hippocampal
      avoidance area. The most common location was frontal lobe. Being younger than 65
      years of age was found to be an independent risk factor for HM (odds ratio: 4.8,
      95% confidence interval: 1-23.2, P = .049). The number of brain metastases was
      significantly higher in patients with hippocampal metastasis ( P = .027), and
      hippocampal metastasis rate was also higher in patients having larger hippocampus
      ( P = .026) and larger brain volumes ( P = .02). CONCLUSION: Hippocampal
      metastasis might be more common in small-cell lung cancer. Reducing the dose to
      the hippocampus by hippocampal avoiding whole-brain radiotherapy plan in small
      cell lung cancer may be risky for the development of HM compared with other
      malignant solid tumors.

PMID- 29332469
TI  - Balance Regularity Among Former High School Football Players With or Without a
      History of Concussion.
AB  - CONTEXT:   Subclinical postural-control changes may persist beyond the point when
      athletes are considered clinically recovered postconcussion. OBJECTIVE:   To
      compare postural-control performance between former high school football players
      with or without a history of concussion using linear and nonlinear metrics.
      DESIGN:   Case-control study. SETTING:   Clinical research laboratory. PATIENTS
      OR OTHER PARTICIPANTS:   A total of 11 former high school football players (age
      range, 45-60 years) with 2 or more concussions and 11 age- and height-matched
      former high school football players without a history of concussion. No
      participant had college or professional football experience. MAIN OUTCOME
      MEASURE(S):   Participants completed the Sensory Organization Test. We compared
      postural control (linear: equilibrium scores; nonlinear: sample and multiscale
      entropy) between groups using a 2 * 3 analysis of variance across conditions 4 to
      6 (4: eyes open, sway-referenced platform; 5: eyes closed, sway-referenced
      platform; 6: eyes open, sway-referenced surround and platform). RESULTS:   We
      observed a group-by-condition interaction effect for medial-lateral sample
      entropy ( F2,40 = 3.26, P = .049, etap2 = 0.140). Participants with a history of
      concussion presented with more regular medial-lateral sample entropy values (0.90
      +/- 0.41) for condition 5 than participants without a history of concussion (1.30
      +/- 0.35; mean difference = -0.40; 95% confidence interval [CI] = -0.74, -0.06;
      t20 = -2.48, P = .02), but conditions 4 (mean difference = -0.11; 95% CI: -0.37,
      0.15; t20 = -0.86, P = .40) and 6 (mean difference = -0.25; 95% CI: -0.55, 0.06;
      t20 = -1.66, P = .11) did not differ between groups. CONCLUSIONS:  
      Postconcussion deficits, detected using nonlinear metrics, may persist long after
      injury resolution. Subclinical concussion deficits may persist for years beyond
      clinical concussion recovery.

PMID- 29332468
TI  - Local Radiotherapy Affects Drug Pharmacokinetics-Exploration of a Neglected but
      Significant Uncertainty of Cancer Therapy.
AB  - PURPOSE: Concurrent chemoradiation therapy is the mainstay of treatment for many
      types of malignancies. However, concurrent chemoradiation therapy is associated
      with a greater number of systemic adverse effects than radiotherapy or
      chemotherapy alone. SUMMARY: Pharmacokinetics is the study of a drug and/or its
      metabolite kinetics in the body, including absorption, distribution, metabolism,
      and elimination. The incidences of adverse effects are markedly higher in
      patients who receive concurrent chemoradiation therapy than in those who receive
      either radiotherapy or chemotherapy alone. This phenomenon implies that
      irradiation affects the pharmacokinetics of cytotoxic agents, namely the
      radiotherapy-pharmacokinetic phenomenon. Experimental animal studies have shown
      that local irradiation affects the systemic pharmacokinetics of 5-fluorouracil
      and cisplatin at both low dose (simulating generous dose distributed to normal
      tissues) and daily practice dose (mimicking therapeutic dose to target volumes).
      These effects are significant in the circulation of blood and lymphatic system as
      well as in the hepatobiliary excretion. Furthermore, recent studies have
      demonstrated that matrix metalloproteinase-8 plays an important role in the
      radiotherapy-pharmacokinetic phenomenon. CONCLUSION: In the present review, we
      provide a general overview of the radiotherapy-pharmacokinetic phenomenon and
      discuss the possible mechanisms governing the phenomenon.

PMID- 29332470
TI  - A School-Based Neuromuscular Training Program and Sport-Related Injury Incidence:
      A Prospective Randomized Controlled Clinical Trial.
AB  - CONTEXT:   An estimated 40 million school-aged children (age range = 5-18 years)
      participate annually in sports in the United States, generating approximately 4
      million sport-related injuries and requiring 2.6 million emergency department
      visits at a cost of nearly $2 billion. OBJECTIVE:   To determine the effects of a
      school-based neuromuscular training (NMT) program on sport-related injury
      incidence across 3 sports at the high school and middle school levels, focusing
      particularly on knee and ankle injuries. DESIGN:   Randomized controlled clinical
      trial. SETTING:   A total of 5 middle schools and 4 high schools in a single
      county public school district. PATIENTS OR OTHER PARTICIPANTS:   A total of 474
      girls (222 middle school, 252 high school; age = 14.0 +/- 1.7 years, height =
      161.0 +/- 8.1 cm, mass = 55.4 +/- 12.2 kg) were cluster randomized to an NMT
      (CORE; n = 259 athletes) or sham (SHAM; n = 215 athletes) intervention group by
      team within each sport (basketball, soccer, and volleyball). INTERVENTION(S):  
      The CORE intervention consisted of exercises focused on the trunk and lower
      extremity, whereas the SHAM protocol consisted of resisted running using elastic
      bands. Each intervention was implemented at the start of the season and continued
      until the last competition. An athletic trainer evaluated athletes weekly for
      sport-related injuries. The coach recorded each athlete-exposure (AE), which was
      defined as 1 athlete participating in 1 coach-directed session (game or
      practice). MAIN OUTCOME MEASURE(S):   Injury rates were calculated overall, by
      sport, and by competition level. We also calculated rates of specific knee and
      ankle injuries. A mixed-model approach was used to account for multiple injuries
      per athlete. RESULTS:   Overall, the CORE group reported 107 injuries (rate =
      5.34 injuries/1000 AEs), and the SHAM group reported 134 injuries (rate = 8.54
      injuries/1000 AEs; F1,578 = 18.65, P < .001). Basketball (rate = 4.99
      injuries/1000 AEs) and volleyball (rate = 5.74 injuries/1000 AEs) athletes in the
      CORE group demonstrated lower injury incidences than basketball (rate = 7.72
      injuries/1000 AEs) and volleyball (rate = 11.63 injuries/1000 AEs; F1,275 = 9.46,
      P = .002 and F1,149 = 11.36, P = .001, respectively) athletes in the SHAM group.
      The CORE intervention appeared to have a greater protective effect on knee
      injuries at the middle school level (knee-injury incidence rate = 4.16
      injuries/1000 AEs) than the SHAM intervention (knee-injury incidence rate = 7.04
      injuries/1000 AEs; F1,261 = 5.36, P = .02). We did not observe differences
      between groups for ankle injuries ( F1,578 = 1.02, P = .31). CONCLUSIONS:  
      Participation in an NMT intervention program resulted in a reduced injury
      incidence relative to participation in a SHAM intervention. This protective
      benefit of NMT was demonstrated at both the high school and middle school levels.

PMID- 29332471
TI  - Fatal Exertional Heat Stroke and American Football Players: The Need for Regional
      Heat-Safety Guidelines.
AB  - CONTEXT:   Weather-based activity modification in athletics is an important way
      to minimize heat illnesses. However, many commonly used heat-safety guidelines
      include a uniform set of heat-stress thresholds that do not account for
      geographic differences in acclimatization. OBJECTIVE:   To determine if heat
      related fatalities among American football players occurred on days with
      unusually stressful weather conditions based on the local climate and to assess
      the need for regional heat-safety guidelines. DESIGN:   Cross-sectional study.
      SETTING:   Data from incidents of fatal exertional heat stroke (EHS) in American
      football players were obtained from the National Center for Catastrophic Sport
      Injury Research and the Korey Stringer Institute. PATIENTS OR OTHER PARTICIPANTS:
      Sixty-one American football players at all levels of competition with fatal
      EHSs from 1980 to 2014. MAIN OUTCOME MEASURE(S):   We used the wet bulb globe
      temperature (WBGT) and a z-score WBGT standardized to local climate conditions
      from 1991 to 2010 to assess the absolute and relative magnitudes of heat stress,
      respectively. RESULTS:   We observed a poleward decrease in exposure WBGTs during
      fatal EHSs. In milder climates, 80% of cases occurred at above-average WBGTs, and
      50% occurred at WBGTs greater than 1 standard deviation from the long-term mean;
      however, in hotter climates, half of the cases occurred at near average or below
      average WBGTs. CONCLUSIONS:   The combination of lower exposure WBGTs and
      frequent extreme climatic values in milder climates during fatal EHSs indicates
      the need for regional activity-modification guidelines with lower, climatically
      appropriate weather-based thresholds. Established activity-modification
      guidelines, such as those from the American College of Sports Medicine, work well
      in the hotter climates, such as the southern United States, where hot and humid
      weather conditions are common.

PMID- 29332472
TI  - Statistical Primer for Athletic Trainers: The Essentials of Understanding
      Measures of Reliability and Minimal Important Change.
AB  - OBJECTIVE:   To describe the concepts of measurement reliability and minimal
      important change. BACKGROUND:   All measurements have some magnitude of error.
      Because clinical practice involves measurement, clinicians need to understand
      measurement reliability. The reliability of an instrument is integral in
      determining if a change in patient status is meaningful. DESCRIPTION:  
      Measurement reliability is the extent to which a test result is consistent and
      free of error. Three perspectives of reliability-relative reliability, systematic
      bias, and absolute reliability-are often reported. However, absolute reliability
      statistics, such as the minimal detectable difference, are most relevant to
      clinicians because they provide an expected error estimate. The minimal important
      difference is the smallest change in a treatment outcome that the patient would
      identify as important. RECOMMENDATIONS:   Clinicians should use absolute
      reliability characteristics, preferably the minimal detectable difference, to
      determine the extent of error around a patient's measurement. The minimal
      detectable difference, coupled with an appropriately estimated minimal important
      difference, can assist the practitioner in identifying clinically meaningful
      changes in patients.

PMID- 29332474
TI  - THE MARINE BIOLOGICAL LABORATORY.

PMID- 29332473
TI  - THE NUTRITION OF PARANEMERTES PEREGRINA (RHYNCHOCOELA: HOPLONEMERTEA). II.
      OBSERVATIONS ON THE STRUCTURE OF THE GUT AND PROBOSCIS, SITE AND SEQUENCE OF
      DIGESTION, AND FOOD RESERVES.
AB  - 1. Digestion in the hoplonemertean Paranemertes peregrina is achieved by a
      combination of extra- and intracellular processes. The extracellular phase,
      effected in an acidic medium, involves endopeptidases secreted by the
      gastrodermal columnar cells, and other, as yet unidentified, substances
      discharged from the intestinal gland cells. The semi-digested food is then
      phagocytosed and digestion completed intracellularly by peptidases, carbohydrases
      and lipases acting in harmony. Intracellular digestion is initially acid and then
      alkaline, with acid and alkaline phosphatases associated with the appropriate
      phases. 2. Nereids used as food are caught by the proboscis, and immobilized by
      secretions produced by the posterior proboscis gland cells. These secretions are
      pumped into the body of the prey via wounds caused by the central stylet. The
      nature of these secretions has not definitely been established, but they may
      contain the toxin anabaseine. 3. The anterior proboscis secretions are concerned
      with aiding the grip of the proboscis papillae and possibly with initiating the
      denaturation of the prey epidermis. 4. Acid secretions are produced by the
      foregut via a mechanism that does not involve carbonic anhydrase. 5. Other sites
      of enzymic activity have been reported, and where possible suggestions made as to
      their probable roles. 6. Fat forms the principal food reserve, with major
      deposits being stored in the gastrodermal columnar cells, but some glycogen is
      stored in a variety of body tissues.

PMID- 29332475
TI  - THE EVALUATION OF THE "CALLIPHORA TEST" AS AN ASSAY FOR ECDYSONE.
AB  - 1. The effect of ligation on pupariation in the front or hind parts of larvae of
      four species of flies, Calliphora erythrocephala, Phormia regina, Sarcophaga
      bullata, and S. argyrostoma was investigated. Ligation causes effects of delay or
      inhibition of pupariation which are very differently expressed in the four
      species. A large proportion of pre- or postcritically ligated specimens of P.
      regina and S. bullata altogether fail to pupariate in the anterior part. This
      makes these species unsuitable test subjects for the pupariation test for
      ecdysone. 2. Test abdomens of C. erythrocephala required significantly less
      ecdysone for a given pupariation effect when also injected with a CNS-extract.
      Tanning was also considerably accelerated in this case. 3. The value of the
      pupariation unit of ecdysone is influenced by a number of factors, such as age at
      the time of ligation, the waiting period between ligation and injection, the
      dilution effect of the solvent, and the simultaneous action of a neurohormone.
      The requirements for natural ecdysone in normal larvae at the time of pupariation
      are probably substantially lower than the values which have been determined by
      others with test abdomens and the use of synthetic ecdysones. 4. In confirmation
      of older data, and contrary to recent claims, tanning was induced in test
      abdomens of the larvae of C. erythrocephala, P. regina, and S. argyrostoma by the
      injection of hemolymph from pupariating larvae. Calliphora blood induced tanning
      in specimens of S. argyrostoma, and vice versa. The conclusions are drawn that
      differences between the different species in the action of ecdysone are of a
      quantitative rather than qualitative nature.

PMID- 29332476
TI  - CALCIFICATION IN ECHINODERMS: EFFECTS OF TEMPERATURE AND DIAMOX ON INCORPORATION
      OF CALCIUM-45 IN VITRO BY REGENERATING SPINES OF STRONGYLOCENTROTUS PURPURATUS.
AB  - 1. Calcification during regeneration of experimentally fractured spines of the
      sea urchin, Strongylocentrotus purpuratus (Stimpson), was studied quantitatively
      under different conditions with calcium-45 as a tracer. 2. Fractured spines
      rapidly incorporated 45Ca in vivo or in vitro after a lag period of about two
      days. The lag period is attributed to wound healing and reorganization of tissue
      at the site of fracture. 3. Additional experiments were conducted while
      calcification was in progress by allowing fractured spines to regenerate for four
      days in vivo followed by incubation in 45Ca in vivo or in vitro up to 24 hours.
      In these experiments incorporation of the label was nearly linear with time and
      no significant difference was observed in the rate of uptake of 45Ca between
      regenerating spines incubated in vivo and those from the same urchin incubated
      simultaneously in vitro. 4. Incorporation of 45Ca in vitro was directly
      proportional to temperature between 4.7 degrees  and 20 degrees  C, at which a
      maximum occurred. A temperature of 26 degrees  C appeared to be lethal and little
      incorporation of 45Ca took place. Values of Q10 and the energy of activation
      varied inversely with temperature, with overall means of 2.72 and 15,504 calories
      per mole, respectively, between 4.7 degrees  and 20 degrees  C. 5. Diamox
      (acetazolamide) at concentrations from 10-3 to 10-6 M, inhibited incorporation of
      45Ca in vitro by 50% to 61%. It is inferred from these results that carbonic
      anhydrase is involved in calcification of regenerating spines of S. purpuratus.

PMID- 29332477
TI  - A COMPARATIVE STUDY OF THE CEMENT GLANDS IN SOME BALANID BARNACLES (CIRRIPEDIA,
      BALANIDAE).
AB  - 1. The histological characteristics of the cement gland cells of barnacles have
      been compared in B. nubilis, B. psittacus, B. eburneus, B. balanoides and B.
      amphitrite. 2. In B. balanoides, the cement gland cells show a very simple
      composition; they are situated at the base of the animal and the secretion
      appears scattered throughout the cytoplasm. The cement apparatus of B. amphitrite
      and B. eburneus looks like that of B. tintinnabulum, but in B. psittacus and B.
      nubilis the cement gland cells appear more complex. 3. The extrusion of the
      cement secretion is brought about by muscle fibers that pass through the
      connective tissue, and in B. psittacus and B. nubilis by elastic fibers around
      the secondary and principal canal systems.

PMID- 29332478
TI  - LARVAL DEVELOPMENT OF PAGURUS LONGICARPUS SAY REARED IN THE LABORATORY, I.
      DESCRIPTION OF LARVAL INSTARS.

PMID- 29332479
TI  - LIFE CYCLE OF THE HYDROMEDUSA PHIALIDIUM GREGARIUM (A. AGASSIZ, 1862) IN THE
      LABORATORY.
AB  - 1. A method was described by which hydroid colonies, each on a microscopic slide,
      were raised from individual planulae of the leptomedusa known as Phialidium
      gregarium. 2. Growth and behavior of approximately 30 cultures were observed and
      quantitated through nearly 2 months. Cultures produced gonangia and medusae 3-7
      weeks after fertilization of the egg. 3. Gonosome development was always preceded
      by a burst of hydroid development 5-9 days previously. This burst appeared to be
      initiated entirely by an abundant food supply (brine shrimp). 4. Medusae were
      liberated 4-5 days after gonangia first appeared. From the growth rate of medusae
      under the less than optimal laboratory conditions, it was estimated that sexual
      maturity may be reached in approximately 3 weeks. The lifespan of the medusae
      probably does not exceed 3 months. 5. A small number of cultures wintered in an
      open cage in the sea. At the end of November they were found in a greatly reduced
      state and possessed only a very few, very small hydranths. At the end of March
      they were in the early phases of vigorous trophosomal growth and the gonosome had
      just begun to flourish. 6. From the behavior of clonal colonies in the
      laboratory, the hypothesis was derived that the swarms of mature medusae in
      nature are the direct result of a "bloom" in zooplankton which occurred 5-7 weeks
      previously and stimulated first hydroid development and in consequence the
      formation of gonangia. 7. Morphological characteristics of the hydroid colonies
      were described and their variability under laboratory conditions recorded and
      discussed. It was shown that many taxonomic features such as size, branching,
      number of tentacles and annulations depend quantitatively on the age of the
      individual colony, its state of nutrition and on genetic factors. 8. The hydroid
      belongs to the genus Clytia (Lamouroux, 1816). A careful comparison was made with
      species of the genus as described for the Puget Sound region and California. It
      was concluded that none of these delineates unambiguously the morphological
      features of this hydroid. A tentative name for the hydroid was assigned according
      to priority principles as Clytia gregaria. It was suggested that Phialidium
      gregarium may be the most appropriate name for the species in both its phases.

PMID- 29332480
TI  - NATURAL AND SYNTHETIC MATERIALS WITH INSECT HORMONE ACTIVITY. 5. SPECIFIC
      JUVENILE HORMONE EFFECTS IN ALIPHATIC SESQUITERPENES.
AB  - The juvenile hormone activity of ethyl or methyl esters of aliphatic
      sesquiterpenic acids with 0 to 4 double bonds was tested on 8 species of insects
      belonging to 5 families of Hemiptera and Coleoptera. Special attention was paid
      to the addition of hydrogen chloride or epoxide groups on or across the double
      bonds. Certain chemical changes in the molecule appear to cause a general
      increase of the activity in all species studied. These are: the presence of 2,3
      unsaturation conjugated with the carboxyl group; the trans stereochemical
      position of the C-3 methyl; an introduction of 10,11 epoxide or hydrochloride;
      and esterification with ethyl rather than with methyl. There are also chemical
      changes which lead to genus- or family-specific variations in juvenile hormone
      activity. With increasing amount of unsaturation the activity either remains
      almost unaffected (pyrrhocorid bugs) or increases (pentatomid bugs) or decreases
      considerably (tenebrionid and dermestid beetles). The addition of hydrogen
      chloride or epoxide to the 6,7 double bond causes enormous increase in the
      activity in the Pyrrhocoridae and Lygaeidae, no considerable change in the
      Pentatomidae, and great decreases in the beetles and Lepidoptera.

PMID- 29332481
TI  - THE NUTRITION OF PARANEMERTES PEREGRINA (RHYNCHOCOELA: HOPLONEMERTEA). I. STUDIES
      ON FOOD AND FEEDING BEHAVIOR.
AB  - 1. Paranemertes peregrina, an abundant hoplonemertean in rocky and muddy
      intertidal habitats of Washington, feeds on polychaetes during low tide periods.
      2. Feeding by Paranemertes involves three steps. The first stage is a recoil of
      the Paranemertes' head upon contact with a prey. Contact must be made with the
      prey; Paranemertes does not find prey by distance chemoreception. The proboscis
      is everted and wraps around the prey in step two. The prey is temporarily
      paralyzed or is killed. In step three the prey is ingested by means of sucking
      motions from muscles around the mouth. Defecation occurs from 12 to 33 hours
      after feeding. 3. Specimens of Paranemertes ate mainly nereid polychaetes at the
      three study areas where nereids were available. At the fourth study area the
      nemerteans ate a wider variety of polychaetes. Experiments to test food
      preference showed that specimens of Paranemertes from all study areas strongly
      preferred nereids to members of other polychaete families. 4. Nereid polychaetes
      have a swimming escape response from Paranemertes.

PMID- 29332482
TI  - EFFECTS OF SUPERABUNDANT OXYGEN ON THERMAL TOLERANCE OF GOLDFISH.
AB  - A hypothesis may be made out that the respiratory/circulatory, and possibly the
      oxygen transport, systems are importantly involved in thermal death of goldfish.
      Experiments showed that at two distinct levels of temperature acclimation,
      superabundant oxygen in the water could produce a definite improvement either in
      time of survival at a fixed lethal temperature or in lethal temperature reached
      as a result of heating. Despite this positive effect of high oxygen a clear cut
      failure of oxygen, in excess of about 5 atmospheres (partial pressure), to
      produce further improvement in thermal tolerance suggests the failure of some
      critical system directly affected by temperature. The experiments, while
      revealing nothing of the detailed mechanisms involved, certainly do not
      invalidate the hypothesis proposed, and open a way to further investigation.

PMID- 29332483
TI  - ENVIRONMENTAL TEMPERATURE AND THYROID ACTIVITY IN THE LIZARD, SCELOPORUS
      OCCIDENTALIS.
AB  - The relationship between temperature and the hypophyseal-thyroidal axis in
      Sceloporus occidentalis has been investigated by a study of radioiodine
      incorporation by the thyroid in intact animals, and animals with the pars
      distalis removed, kept at temperatures of 15 degrees , 21 degrees , 30 degrees 
      and 38 degrees  C. Over the range of 21 to 38 degrees  C there was no evidence of
      any significant temperature-related change in the normal and experimental
      animals, although the thyroid activity was reduced after the operation. At 15
      degrees  C the thyroid functioning was significantly inhibited and there was no
      difference between the normal and experimental animals. It is suggested that the
      role of temperature in thyroid activation is a permissive one. Data for I131
      incorporation in hypophysectomized animals receiving TSH therapy offers a
      possible explanation for the different patterns of thyroidal I131 accumulation
      observed in different forms of lizards.

PMID- 29332484
TI  - EMERSION OF THE AMPHIBIOUS CHILEAN CLINGFISH, SICYASES SANGUINEUS.
AB  - The amphibious clingfish Sicyases sanguineus attaches by means of its ventral
      sucker to vertical surfaces of large exposed rocks splashed by the cool and heavy
      surf of Chile and southern Peru. Although adult and halfgrown fish tolerate
      diluted seawater and can survive at least a few hours in warm and stagnant water,
      they seldom, if ever, occur in isolated tidal pools, bays, or estuaries. Factor
      analysis indicates that clingfish come out of the water more abundantly during
      periods of calm and often turn head-down. They avoid drying rocks outside the
      spray zone and emerge onto higher rocks as the water level rises. Adult fish come
      out of the water more abundantly in remote areas relatively undisturbed by
      civilization. Insolation apparently does not directly alter the abundance of
      clingfish, which act so as to minimize evaporative water loss and overheating.
      Terrestrial fish breathe air held in their gill cavities, probably through their
      gills. As they come out of the water, fish gulp air, then stop all opercular
      movements to seal their cavities, and often turn head-down. This positioning may
      facilitate airbreathing by easing the expulsion of spent gas upward through the
      watery gill cavities and by shading an area of delicate respiratory epithelium
      under the chin. The volume percentage oxygen in gas expelled into a viscous
      solution of resin in sea water decreased regularly for about 12 minutes in a
      young fish, about 30 minutes in a halfgrown fish, and about one hour in an adult
      before these fish renewed their branchial gas. Although a concomitant increase in
      percentage carbon dioxide indicated that the branchial gas contributed to
      respiration, rates of oxygen uptake calculated from modal volumes of expelled gas
      were only about 12-30% of the fish's total long-term rate in air as determined by
      other investigators. As in other airbreathing fishes, however, cutaneous
      respiration may supplement branchial respiration, which fills the total need only
      when the metabolic rate falls. Exposure of their head apparently stimulates
      clingfish to gulp, so that atmospheric air, rather than aquatic hypoxia, is their
      primary stimulation to airbreathing. Fish in stagnating water do not necessarily
      emerge and occasionally remain under water until they suffocate. Like other
      airbreathing fishes, clingfish appear insensitive to relatively large proportions
      of carbon dioxide in their branchial gas. And even with their opercles closed and
      their ventral mouths pressed against the substrate, clingfish in the field should
      easily eliminate excess carbon dioxide through their wet skin. Vargas and Concha
      (1957a) emphasized the ontogenesis of terrestriality in clingfish from erratic
      young to well-regulated adult: modification of gill surface to minimize clumping,
      control of aerial oxygen uptake, and greater composure on land. The present study
      indicates that exposure of an anteroventral respiratory membrane, assumption of a
      head-down position, improvement of gulping technique, control and slowing of
      ventilation, and greater efficiency of exchange between branchial gas and blood
      also contribute critically to the maturing fish's increasing independence of
      aquatic life.

PMID- 29332486
TI  - PSPB Editorial Philosophy.

PMID- 29332485
TI  - Relationship between neutrophil/lymphocyte ratio and epicardial fat tissue
      thickness in patients with newly diagnosed hypertension.
AB  - Objective Epicardial fat tissue thickness (EFT) and the neutrophil/lymphocyte
      ratio (NLR) are associated with atherosclerosis. Few studies have focused on the
      relationship between these parameters in patients with newly diagnosed
      hypertension. In this study, we examined the relationship between EFT and the NLR
      in patients with newly diagnosed hypertension detected by 24-hour ambulatory
      blood pressure monitoring (ABPM). Methods Eighty consecutive patients without
      chronic illness who were diagnosed with hypertension according to ABPM results
      and 80 otherwise healthy subjects were enrolled in the study. EFT of each
      participant was measured echocardiographically. The C-reactive protein (CRP)
      concentration and NLR were measured from venous blood samples. Results The 24
      hour average systolic blood pressure was significantly higher in the hypertension
      group than in the control group (143+/-17 vs. 117+/-7 mmHg, respectively). There
      were no significant differences in age, sex, or body mass index between the two
      groups. EFT, the NLR, and the CRP concentration were significantly higher in the
      hypertension group than control group. Additionally, a significantly positive
      correlation between EFT and the NLR was found in both the control group and
      hypertension group. Conclusion A higher EFT and NLR were detected in patients
      with newly diagnosed hypertension than in healthy subjects.

PMID- 29332487
TI  - The Prototypical Majority Effect Under Social Influence.
AB  - Majority views are reported with greater confidence and fluency than minority
      views, with the difference increasing with majority size. This Prototypical
      Majority Effect (PME) was attributed generally to conformity pressure, but Koriat
      et al. showed that it can arise from the processes underlying decision and
      confidence independent of social influence. Here we examined the PME under
      conditions that differ in social influence. In Experiment 1, a robust PME emerged
      in the absence of information about the majority views, but the provision sof
      that information increased the choice of the majority view and magnified the PME.
      In Experiment 2, a PME emerged in a minority-biased condition that misled
      participants to believe that the majority view was the minority view, but the PME
      was stronger in a majority-biased condition. The results were discussed in terms
      of a dual-process view: The PME observed under social influence may contain
      externally driven and internally driven components.

PMID- 29332489
TI  - Thermoacoustic Lensing in Ultrasound Imaging of Nonechogenic Tissue During High
      intensity Focused Ultrasound Exposure.
AB  - We develop a ray-tracing theory to describe the effects of thermoacoustic lensing
      during high-intensity focused ultrasound (HIFU) on ultrasound images of
      reflectors lying distal to the HIFU focal region and discuss the application of
      thermal lensing effects to dose monitoring in HIFU therapy. By analyzing the
      effects of thermal and geometric delays of acoustic rays passing through a region
      of tissue undergoing localized heating, we show how the shape of a reflector
      distal to the heated region can be predicted and present experimental
      measurements in good agreement with the model. We also apply the model in reverse
      to estimate the thermal profile of a heated region based on a measured change in
      the shape of a distal reflector during HIFU delivery. As an example, we apply
      this technique to the measurements of thermal diffusion in porcine fat. An
      interesting aspect of the technique is that it can be applied to measure
      temperature in nonechogenic tissues as long as there is an observable reflector
      in the ultrasound images that is located distal to the region of localized
      heating.

PMID- 29332488
TI  - Role of the hippocampal 5-HT1A receptor-mediated cAMP/PKA signalling pathway in
      sevoflurane-induced cognitivedysfunction in aged rats.
AB  - Objective This study aimed to evaluate the role of the hippocampal 5
      hydroxytryptamine-1A (5-HT1A)-mediated cyclic adenosine monophosphate/protein
      kinase A (cAMP/PKA) signalling pathway in sevoflurane-induced cognitive
      dysfunction in aged rats. Methods Sixty 18-month-old Sprague-Dawley rats were
      divided into the control (n = 30) and experimental (Sev, n = 30) groups. The
      experimental group inhaled 50% air/oxygen mixture (2 L/min) and 2% sevoflurane
      for 4 hours. The control group inhaled 50% air/oxygen mixture (2 L/min) for 4
      hours. The Morris water maze test was performed The mRNA expression of 5-HT1A
      receptor, and cAMP PKA, cAMP response element-binding protein (CREB), and
      phosphorylated CREB (p-CREB) protein expression were determined. Results The
      escape latency and swimming distance were greater, and the number of crossings of
      the platform location and time spent in the platform quadrant were less in the
      Sev group compared with the control group. cAMP, PKA, CREB, and p-CREB protein
      expression was downregulated in the Sev group 1 day after anaesthesia compared
      with the control group. Hippocampal 5-HT1A receptor mRNA expression was higher 7
      days after anaesthesia compared with the control group. Conclusion Sevoflurane
      induced cognitive dysfunction in aged rats may be related to inhibited expression
      of the hippocampal 5-HT1A receptor-mediated cAMP/PKA signalling pathway.

PMID- 29332490
TI  - The Oppression of Latina Mothers: Experiences of Exploitation, Violence,
      Marginalization, Cultural Imperialism, and Powerlessness in Their Everyday Lives.
AB  - Despite Latinos being the largest growing population in the United States,
      research has not examined the impact of social structures on the well-being of
      Latina immigrants; negative social discourse and restrictive laws exacerbate
      inequality and discrimination in this population. Through combined
      inductive/deductive analysis of in-depth semistructured interviews, we examined
      immigrant Mexican mothers' ( N = 32) descriptions of oppression in the United
      States. All five forms of oppression, described in Young's oppression framework
      are evident: exploitation, violence, marginalization, cultural imperialism, and
      powerlessness. Discrimination places a high burden on Latinas due to the
      intersection of forms of oppression and nondominant identities.

PMID- 29332491
TI  - Relationship (A)Symmetries and Violence: Comparing Intimates and NonPartners.
AB  - Violence between social equals differs in character from violence between persons
      in asymmetrical relationships. Specifically, issues of contention motivating
      violence vary by the relative status of opponents, such that violence over
      symbolic issues is more common between symmetrical than asymmetrical opponents.
      Recent studies have substantiated these predictions in nonpartner relationships.
      Using data from interviews of incarcerated women, this study explores how
      intimate partner violence compares with violence between nonpartner opponents. We
      find that intimate partner violence is more likely to involve symbolic issues
      compared with violence between all kinds of nonpartner opponents. Consequently,
      intimate partnerships might be viewed as hypersymmetrical.

PMID- 29332492
TI  - Safety and efficacy of photoselective vaporization of the prostate using the 180
      W GreenLight XPS laser system in patients taking oral anticoagulants.
AB  - Objective To evaluate the safety and efficacy of the 180-W GreenLight XPS laser
      system for the treatment of benign prostatic hyperplasia in patients taking oral
      anticoagulants. Methods All consecutive patients admitted for lower urinary tract
      symptoms associated with benign prostatic hyperplasia from November 2012 to
      October 2016 and who underwent photoselective vaporization of the prostate with
      the 180-W GreenLight XPS laser were included in the study. The perioperative
      outcomes examined were the operating time, laser time, energy usage, and duration
      of postoperative catheterization. Functional parameters (International Prostate
      Symptom Score, maximum urinary flow rate, and post-void residual urine volume),
      prostate volume, and serum prostate-specific antigen concentration were examined
      at baseline and 3 months. Perioperative complications, if any, were noted.
      Results All functional parameters (International Prostate Symptom Score, maximum
      urinary flow rate, and post-void residual urine volume) significantly improved
      from baseline to 3 months. A small number of patients experienced at least one
      minor adverse event. There was no difference in the rate of adverse events
      between patients who were and were not taking anticoagulants. Conclusions
      Photoselective vaporization with a 180-W laser is an efficacious and safe
      treatment for benign prostatic hyperplasia, even in patients taking anticoagulant
      medications.

PMID- 29332493
TI  - College Campus Sexual Assault: The Contribution of Peers' Proabuse Informational
      Support and Attachments to Abusive Peers.
AB  - Since the mid-1980s, researchers across the United States have uncovered high
      rates of sexual assault among female college students. However, to advance a
      better understanding of this gendered type of victimization, and to both prevent
      and control this problem, the research community needs to identify its major
      correlates. One that is consistently uncovered in North American campus survey
      work is negative peer support, especially that provided by male peers. Yet, some
      earlier studies have found that mixed-sex negative peer support, too, contributes
      to campus sexual assault. Using recent data from the Campus Quality of Life
      Survey conducted at a large residential school in the South Atlantic region of
      the United States, the main objectives of this article are to examine the role of
      mixed-sex negative peer support in campus sexual assault and to identify the
      groups of women most at risk of having friends who offer such support.

PMID- 29332494
TI  - An Evaluation of Adolescent and Young Adult (Re)Victimization Experiences:
      Problematic Substance Use and Negative Consequences.
AB  - We investigated substance use and negative consequences in women who experienced
      an initial sexual assault (SA) in high school and subsequently in college. More
      than 650 participants completed questionnaires assessing substance
      use/consequences, SA history, and posttraumatic stress disorder (PTSD)
      symptomology. Revictimized women reported differential substance use/consequences
      relative to controls underscoring the need to conceptualize adolescence as a key
      developmental period with a unique pathway to a subsequent SA, especially in
      association with substance use. We propose that prevention interventions should
      begin no later than ninth grade to limit the risk for an initial experience of SA
      and any consequential substance use and abuse.

PMID- 29332495
TI  - Comparing Violent Victimization Experiences of Male and Female College-Attending
      Emerging Adults.
AB  - Despite increased attention to college student victimization, gaps remain. In
      particular, relatively little is known about violence against males and females
      outside sexual and intimate partner violence. This study uses data from the
      National Crime Victimization Survey to compare male and female students' violent
      victimization overall as well as relational and sexual violence. Findings reveal
      gendered differences and similarities. Results have implications for policies to
      prevent violence and support victims. Implications for victim services are
      particularly relevant given the critical developmental period for college
      students learning coping skills that shape their adult lives and addressing harms
      resulting from violent victimization.

PMID- 29332496
TI  - Double Jeopardy: Insurance, Animal Harm, and Domestic Violence.
AB  - Although the role of companion animals within the dynamic of domestic violence
      (DV) is increasingly recognized, the overlap of animal harm and insurance
      discrimination for victims/survivors of DV has not been considered. Prompted by a
      case study presented in a National Link Coalition LINK-Letter, this research note
      examines "Pet Insurance" policies available in Australia and whether
      nonaccidental injury caused by an intimate partner would be covered. We discuss
      the implications of exclusion criteria for victims/survivors of DV, shelters
      providing places for animals within a DV dynamic, and, more broadly, for cross-
      or mandatory-reporting (of animal harm) initiatives.

PMID- 29332498
TI  - An Updated Assessment of Personal Protective Order Statutes in the United States:
      Have Statutes Become More Progressive in the Past Decade?
AB  - The Personal Protection Order (PPO) is one civil intervention all states provide
      to victims of domestic violence; however, each state varies widely in who can
      access PPOs, what protections are included in PPOs, and how they are enforced.
      Given the many changes to state PPO statutes over the last decade, this research
      replicates and updates DeJong and Burgess-Proctor's research on PPOs' victim
      friendliness (using states' 2003 PPO statutes) by examining states' 2014 PPO
      statutes. Findings suggest that states have become more victim-friendly with most
      states ranking in the highest category of victim-friendliness. Implications for
      policy and practice are discussed.

PMID- 29332497
TI  - Dosimetric Analysis of Microscopic Disease in SBRT for Lung Cancers.
AB  - OBJECTIVE: The objective of this study is to theoretically and experimentally
      evaluate the dosimetry in the microscopic disease regions surrounding the tumor
      under stereotactic body radiation therapy of lung cancer. METHODS: For
      simplicity, the tumor was considered moving along 1 dimension with a periodic
      function. The probability distribution function of the tumor position was
      generated according to the motion pattern and was used to estimate the delivered
      dose in the microscopic disease region. An experimental measurement was conducted
      to validate both the estimated dose with a probability function and the
      calculated dose from 4-dimensional computed tomography data using a dynamic
      thorax phantom. Four tumor motion patterns were simulated with cos4(x) and
      sin(x), each with 2 different amplitudes: 10 mm and 5 mm. A 7-field conformal
      plan was created for treatment delivery. Both films (EBT2) and optically
      stimulated luminescence detectors were inserted in and around the target of the
      phantom to measure the delivered doses. Dose differences were evaluated using
      gamma analysis with 3%/3 mm. RESULTS: The average gamma index between measured
      doses using film and calculated doses using average intensity projection
      simulation computed tomography was 80.8% +/- 0.9%. In contrast, between measured
      doses using film and calculated doses accumulated from 10 sets of 4-dimensional
      computed tomography data, it was 98.7% +/- 0.6%. The measured doses using
      optically stimulated luminescence detectors matched very well (within 5% of the
      measurement uncertainty) with the theoretically calculated doses using
      probability distribution function at the corresponding position. Respiratory
      movement caused inadvertent irradiation exposure, with 70% to 80% of the dose
      line wrapped around the 10 mm region outside the target. CONCLUSION: The use of
      static dose calculation in the treatment planning system could substantially
      underestimate the actual delivered dose in the microscopic disease region for a
      moving target. The margin for microscopic disease may be substantially reduced or
      even eliminated for lung stereotactic body radiation therapy.

PMID- 29332499
TI  - Examination of an in vitro methodology to evaluate the biomechanical performance
      of nucleus augmentation in axial compression.
AB  - Intervertebral disc degeneration is one of the leading causes of back pain, but
      treatment options remain limited. Recently, there have been advances in the
      development of biomaterials for nucleus augmentation; however, the testing of
      such materials preclinically has proved challenging. The aim of this study was to
      develop methods for fabricating and testing bone-disc-bone specimens in vitro for
      examining the performance of nucleus augmentation procedures. Control, nucleotomy
      and treated intervertebral disc specimens were fabricated and tested under static
      load. The nucleus was removed from nucleotomy specimens using a trans-endplate
      approach with a bone plug used to restore bony integrity. Specimen-specific
      finite element models were developed to elucidate the reasons for the variations
      observed between control specimens. Although the computational models predicted a
      statistically significant difference between the healthy and nucleotomy groups,
      the differences found experimentally were not significantly different. This is
      likely due to variations in the material properties, hydration and level of
      annular collapse. The deformation of the bone was also found to be non
      negligible. The study provides a framework for the development of testing
      protocols for nucleus augmentation materials and highlights the need to control
      disc hydration and the length of bone retained to reduce inter-specimen
      variability.

PMID- 29332500
TI  - Microstructure and mechanical properties of porous titanium structures fabricated
      by electron beam melting for cranial implants.
AB  - The traditional methods of metallic bone implants are often dense and suffer from
      adverse reactions, biomechanical mismatch and lack of adequate space for new bone
      tissue to grow into the implant. The objective of this study is to evaluate the
      customized porous cranial implant with mechanical properties closer to that of
      bone and to improve the aesthetic outcome in cranial surgery with precision
      fitting for a better quality of life. Two custom cranial implants (bulk and
      porous) are digitally designed based on the Digital Imaging and Communications in
      Medicine files and fabricated using additive manufacturing. Initially, the
      defective skull model and the implant were fabricated using fused deposition
      modeling for the purpose of dimensional validation. Subsequently, the implant was
      fabricated using titanium alloy (Ti6Al4V extra low interstitial) by electron beam
      melting technology. The electron beam melting-produced body diagonal node
      structure incorporated in cranial implant was evaluated based on its mechanical
      strength and structural characterization. The results show that the electron beam
      melting-produced porous cranial implants provide the necessary framework for the
      bone cells to grow into the pores and mimic the architecture and mechanical
      properties closer to the region of implantation. Scanning electron microscope and
      micro-computed tomography scanning confirm that the produced porous implants have
      a highly regular pattern of porous structure with a fully interconnected network
      channel without any internal defect and voids. The physical properties of the
      titanium porous structure, containing the compressive strength of 61.5 MPa and
      modulus of elasticity being 1.20 GPa, represent a promising means of reducing
      stiffness and stress-shielding effect on the surrounding bone. This study reveals
      that the use of porous structure in cranial reconstruction satisfies the need of
      lighter implants with an adequate mechanical strength and structural
      characteristics, thus restoring better functionality and aesthetic outcomes for
      the patients.

PMID- 29332501
TI  - "Plates and Dishes Smash; Married Couples Clash": Cultural and Social Barriers to
      Help-Seeking Among Women Domestic Violence Survivors in Kyrgyzstan.
AB  - This article develops a grounded theory of help-seeking to investigate the social
      and cultural determinants of help-seeking among Kyrgyz women who have experienced
      domestic violence. Results indicate that cultural traditions and social norms
      most notably the social construction of marriage, the shame associated with
      divorce, and the status of daughters-in-law in Kyrgyz society-are used to justify
      domestic violence and prevent victims from seeking help. The proposed theory and
      results suggest that scholars, policymakers, and front-line contacts must
      emphasize dispelling myths, misconceptions, and traditional beliefs about gender
      and marriage to break the abusive dynamics and provide professional help.

PMID- 29332502
TI  - Associations Between Home Death and the Use and Type of Care at Home.
AB  - Despite wishes for and benefits of home deaths, a discrepancy between preferred
      and actual location of death persists. Provision of home care may be an effective
      policy response to support home deaths. Using the population-based mortality
      follow-back study conducted in Nova Scotia, we investigated the associations
      between home death and formal care at home and between home death and the type of
      formal care at home. We found (1) the use of formal care at home at the end of
      life was associated with home death and (2) the use of formal home support
      services at home was associated with home death among those whose symptoms were
      well managed.

PMID- 29332503
TI  - "They Said on the Death Certificate...But Really What I Think Happened":
      Characterizing Cause of Death in VA Medical Centers.
AB  - Cause of death information is a vital resource for family and public health, yet
      significant issues persist regarding its determination, documentation and
      communication. In this study, we aim to characterize cause of death attribution
      process from the perspective of next-of-kin of Veterans who died in Veterans
      Affairs (VA) Medical Centers. Using a semi-structured guide, we explored next-of
      kin's experiences of the Veteran's terminal hospitalization and conducted a
      content analysis of interview texts. In over two-third of cases next-of-kin's
      understanding was not consistent with their recollection of physicians'
      determination of cause of death. Discrepancies between official cause of death
      and lay understanding engendered confusion and distress. Findings have relevance
      for shaping the context of post-death patient/family-centered clinical practice
      and serve as a means for improving efficacy of cause of death communication and
      reducing potential for misunderstandings.

PMID- 29332504
TI  - Changes in Distress Measured by the Distress Thermometer as Reported by Patients
      in Home Palliative Care in Germany.
AB  - AIM: To identify changes in distress as reported by patients in a home palliative
      care program over a 2-week period. METHODS: Prospective study in West Germany
      with consecutive patients cared for at home by a palliative care specialty team.
      Exclusion criteria were patients under 18 years of age, mentally or physically
      not able to complete the assessment questionnaires, or unable to comprehend
      German language. Distress was measured using the distress thermometer (DT);
      sociodemographic and medical data were collected from the patients' records.
      RESULTS: One hundred three participated in the study (response rate of 69%) and
      39 participants completed DT at 2-week follow-up (T1; response rate = 38%; mean
      age = 67; female = 54.4%; married = 67%; living home with relatives = 60.2%;
      oncological condition = 91.3%; Karnofsky performance status [KPS] 0-40 = 18.9%,
      KPS 50-70 = 70.3%, KPS >80 = 10.8%). The mean DT score at the first visit (T0)
      was 5.9 (2.3), with 82.1% of the participants scoring DT >=5. At the 2-week
      follow-up (T1), mean DT score was 5.0 (2.0), with 64.1% scoring DT >=5, showing a
      statistically significant difference between T0 and T1. Comparing the single
      scores at T0 and T1 of each participant, the difference in DT scores was -0.9
      (2.27). CONCLUSION: The DT is a useful tool for screening severity and changes in
      psychological distress as well as sources of distress. The DT detected change in
      self-reported distress within a short treatment period, indicating success or
      failure of the palliative care treatment approaches.

PMID- 29332505
TI  - Building a Novel Health Curriculum for Survivors of Intimate Partner Violence
      Residing at a Transitional Housing Program.
AB  - We used a community-based participatory research approach to develop, implement,
      and evaluate one of the first health curricula for female intimate partner
      violence (IPV) survivors residing at a transitional housing program. The
      curriculum comprised 12 workshops that were developed based on the survivors'
      experiences, needs, and interests. Evaluation participants included 20 of the 37
      women who attended at least one workshop, 12 workshop facilitators, and two
      housing center staff. Participants found the curriculum to be engaging,
      interactive, and helpful in building a supportive community. Suggestions for
      curricular improvement as well as opportunities for further research and
      curricular development are discussed.

PMID- 29332506
TI  - Rape Crimes: Are Victims' Acute Psychological Distress and Perceived Social
      Support Associated With Police Case Decision and Victim Willingness to
      Participate in the Investigation?
AB  - This study examined level of acute psychological distress and perceived social
      support in 64 victims of rape and the association with police case decisions and
      victims' willingness to participate in the investigation. The results of
      independent-sample t tests revealed that victims' unwillingness to participate in
      the investigation was significantly associated with a higher level of
      psychological distress in the acute phase following the assault. The results
      suggest that victims of rape who disengage with the police investigation may do
      so because of a high level of acute psychological distress. Clinical implications
      are discussed.

PMID- 29332507
TI  - An Evaluation of the Impacts of Changing Firearms Legislation on Australian
      Female Firearm Homicide Victimization Rates.
AB  - Reducing lethal violence against women requires comprehensive measures addressing
      individual, social, economic, cultural, and situational factors. Regarding
      situational factors, access to weapons-and firearm access in particular-has
      received notable research attention. However, most study comes from the United
      States of America, and findings may not apply elsewhere. The current study
      examines whether changing gun laws in Australia affected female firearm homicide
      victimization. Female firearm homicide victimization may have been affected;
      however, no significant impacts were found for male firearm homicide
      victimization. Findings suggest there may be value in preventing legal access to
      firearms by persons who have a history of intimate partner violence, although
      considerable further study is required.

PMID- 29332508
TI  - Battered Wives or Dependent Mothers? Negotiating Familial Ideology in Law.
AB  - More than a decade after its passing, Sri Lanka's Prevention of Domestic Violence
      Act (PDVA) remains a remedy of last resort for female survivors of intimate
      partner violence, as there is little support to take on a rights-defined identity
      as a battered woman both inside and outside the courtroom. However, large numbers
      of women are accessing the Maintenance Act of 1999 to exit violent relationships
      without the censure and stigma that attaches to the PDVA. The key to
      understanding this phenomenon is to consider how familial ideology works in
      unpredictable ways within the Sri Lankan judicial system. This article examines
      the reach and different impacts of familial ideology within the judiciary and
      argues that female survivors of violence navigate this ideology to their own
      advantage. However, the preference to address violence through the Maintenance
      Act renders such violence invisible. The price for judicial redress is silence.

PMID- 29332509
TI  - Sexual Scripts and Criminal Statutes: Gender Restrictions, Spousal Allowances,
      and Victim Accountability After Rape Law Reform.
AB  - The author provides a mixed-methods assessment of U.S. rape statutes to assess
      progress in reform. Contemporary statutes offer restrictive frameworks for
      distinguishing criminal from noncriminal sexual violence, many of which are
      grounded in gendered and heterosexist assumptions. Fourteen states retain gender
      restrictions in rape statutes. Twenty maintain marital distinctions that limit
      accountability for spousal rape. Furthermore, whereas explicit resistance
      requirements have been eliminated nationwide, implicit resistance expectations
      manifest through emphasis on physical force and involuntary intoxication.
      Analyses conclude with recommendations for further legal reform and a discussion
      of the potential for legislation to affect broader social perceptions of rape.

PMID- 29332510
TI  - Localized autoimmune pancreatitis mimicking pancreatic cancer: Case report and
      literature review.
AB  - Autoimmune pancreatitis (AP) is a rare autoimmune pancreatic manifestation of
      systemic immunoglobulin G4 (IgG4)-related sclerosing disease. Distinguishing
      between AP and pancreatic cancer is crucial because the clinical courses,
      treatments, and prognoses of these two disease entities are quite different. We
      herein report a case involving a 52-year-old man with subacute epigastralgia who
      visited our hospital for evaluation of a suspicious pancreatic mass found during
      esophagogastroduodenoscopy. Enhanced computed tomography (CT) revealed an
      enlarged lesion in the pancreatic head with encasement of hepatic vessels. The
      lesion also exhibited increased 18F-fluorodeoxyglucose accumulation on positron
      emission tomography/CT imaging, which was highly suggestive of pancreatic cancer.
      After open biopsy, morphologic examination showed an inflammatory infiltrate in
      the pancreas, which was compatible with chronic sclerotic pancreatitis. Further
      laboratory tests revealed an elevated serum IgG4 level, and the diagnosis of
      sclerotic pancreatitis was then confirmed. After corticosteroid treatment, the
      pancreatic lesion showed shrinkage on follow-up CT, and the serum IgG4 titer
      decreased to the normal range. This case suggests that clinicians should be
      familiar with the clinical presentations and diagnostic criteria of AP versus
      pancreatic cancer. An awareness of the differences between these diseases may
      avoid misdiagnosis and unnecessary surgical intervention.

PMID- 29332511
TI  - The Process of Primary Desistance From Intimate Partner Violence.
AB  - This study examined the interaction between structure and agency for individuals
      in the first or early phase of primary desistance (1 year offending free) from
      intimate partner violence (IPV). Narrative accounts of perpetrators, survivors,
      and IPV program facilitators were analyzed using Thematic Analysis. Changes in
      the self and the contexts, structures, and conditions were necessary to promote
      desistance. Perpetrators made behavioral and cognitive changes taking on
      different identities (agentic role) by removing external stressors and
      instability within the confines of a supportive environment (structural role).
      Findings provide a theoretical framework of desistance from IPV that integrates
      social processes and subjective change.

PMID- 29332512
TI  - Rape Aggression Defense: Unique Self-Efficacy Benefits for Survivors of Sexual
      Trauma.
AB  - Self-defense training is consistently linked to psychological benefits for
      survivors of sexual trauma, yet little is known about how training may uniquely
      benefit survivors compared with their nonsurvivor peers enrolled in the same
      course. Path analysis was used to examine how history of sexual trauma impacts
      pre- and post-training scores on three domains of self-efficacy using a national
      sample of Rape Aggression Defense (RAD) participants. All participants reported
      significant increases in self-efficacy domains, and sexual trauma history
      significantly predicted pre-training interpersonal self-efficacy and post
      training self-defense self-efficacy, suggesting that self-defense training
      confers benefits for survivors above and beyond benefits for other participants.

PMID- 29332513
TI  - The Meaning of Choosing a Spouse Among Ultra-Orthodox Jewish Women Who Found
      Themselves in a Violent Relationship.
AB  - This research note addresses how ultra-Orthodox Jewish women in Israel coping
      with intimate partner violence experienced the spouse selection process. In-depth
      semistructured qualitative-phenomenological interviews were conducted with 17
      women. Four major themes emerged: (a) "The matchmaker seemingly fell asleep on
      her watch"; (b) The parents' mistakes; (c) "The rabbi told me to jump into the
      water. Now he should hand me the paddles to get out!" The rabbi's role; and (d)
      "That's it . . . I follow it blindly": The system. The findings add to the
      professional knowledge about violent partnerships in the ultra-Orthodox Jewish
      community in Israel.

PMID- 29332514
TI  - Gender, Migration, and Exclusionary Citizenship Regimes: Conceptualizing
      Transnational Abandonment of Wives as a Form of Violence Against Women.
AB  - Based on life history narratives of 57 women in India and interviews with 21
      practitioners, we document the neglect, abuse, and instrumental deprivation of
      women's rights through the process of transnational abandonment. While gendered
      local sociocultural milieus and economic norms contribute to these harms, they
      are crucially enabled and sustained by transnational formal-legal frameworks.
      Widening the explanatory lens for understanding domestic violence beyond the
      family and community, we argue that in a globalized world, (inter)state policies
      serve to construct these women as a subordinate category of citizens-"disposable
      women"-who can be abused and abandoned with impunity.

PMID- 29332516
TI  - Drivers of Intimate Partner Violence Against Women in Three Refugee Camps.
AB  - This qualitative study examined the "drivers" of intimate partner violence (IPV)
      against women in displacement to identify protective factors and patterns of
      risk. Qualitative data were collected in three refugee camps in South Sudan,
      Kenya, and Iraq ( N = 284). Findings revealed interrelated factors that triggered
      and perpetuated IPV: gendered social norms and roles, destabilization of gender
      norms and roles, men's substance use, women's separation from family, and rapid
      remarriages and forced marriages. These factors paint a picture of individual,
      family, community and societal processes that exacerbate women's risk of IPV in
      extreme conditions created by displacement. Implications for policy and practice
      are indicated.

PMID- 29332515
TI  - Vasoplegia in patients with sepsis and septic shock: pathways and mechanisms.
AB  - Sepsis is one of the most frequent causes of death among patients in intensive
      care units. Many therapeutic strategies have been assessed without the desired
      success rates. A key risk factor for death is hypotension due to vasodilatation
      with vascular hyposensitivity. However, the pathways underlying this process
      remain unclear. Endotoxemia induces inflammatory mediators, and this is followed
      by vasoplegia and decreased cardiac contractility. Although inhibition of these
      mediators diminishes mortality rates in animal models, this phenomenon has not
      been confirmed in humans. Downregulation of vasoconstrictive receptors such as
      angiotensin receptors, adrenergic and vasopressin receptors is seen in sepsis,
      which is associated with a hyporesponsiveness to vasoconstrictive mediators.
      Animal studies have verified that receptor downregulation is linked to the above
      mentioned inflammatory mediators. Anti-inflammatory therapy with glucocorticoids
      reportedly improves responsiveness to catecholamines with higher survival in
      rats, although this has not been shown to be clinically significant in humans.
      Hence, there is an urgent need for in-depth studies investigating the underlying
      mechanisms of vasoplegia to allow for development of effective therapeutic
      strategies for the treatment of sepsis.

PMID- 29332517
TI  - Women's Decisions to Stay in or Leave an Abusive Relationship: Results From a
      Longitudinal Study in Bolivia.
AB  - This study examined Bolivian women's decisions to stay with or leave their
      violent partners. The theory of planned behavior (TPB) was used as the
      theoretical framework. One hundred thirty-four women were assessed 3 times over 6
      months. The TPB constructs were measured at T1 and T2; relationship status was
      assessed at T3. At T2, attitudes about staying and leaving predicted the
      intention to leave. Intention to leave at T2 but not at T1 predicted relationship
      status at T3. These results suggest that the decision to leave was consolidated
      between T1 and T2, and attitudes toward staying were most relevant to this
      decision.

PMID- 29332518
TI  - Sexual Assault and Dyadic Relationship Satisfaction: Indirect Associations
      Through Intimacy and Mental Health.
AB  - Rates of child and adult sexual assault (SA) among women are staggering and place
      women at risk for intra- and interpersonal difficulties. However, the independent
      contributions of child and adult SA or the mechanisms of this risk are unknown.
      This study's goal was to examine the indirect effects of child and adult SA on
      women's own and partner's relationship functioning through their impact on
      women's mental health, emotional intimacy, and sexual intimacy. Results revealed
      that the association of women's child SA with both her own and her partner's
      relationship satisfaction operated through emotional intimacy. Considerations for
      the study of women with a history of SA in the context of couple functioning are
      discussed.

PMID- 29332519
TI  - Integrating Reproductive Health Services Into Intimate Partner and Sexual
      Violence Victim Service Programs.
AB  - This study assessed the feasibility of integrating reproductive health services
      into intimate partner violence/sexual violence (IPV/SV) programs. After a
      training for victim service agencies on integration of health services, we
      conducted semistructured interviews with IPV/SV program leadership. Leadership
      reported advocates were more likely to recognize the need to refer clients to
      health services, and revealed challenges operationalizing partnerships with
      health care centers. Training to integrate basic health assessment into victim
      services may be one way to address women's urgent health needs. Formal
      partnership agreements, protocols to facilitate referrals, and opportunities to
      cross-train are needed to nurture these cross-sector collaborations.

PMID- 29332520
TI  - Gender-Based Violence Among HIV-Positive Women in Kazakhstan: Prevalence, Types,
      and Associated Risk and Protective Factors.
AB  - This article examines the prevalence and associated multilevel risk and
      protective factors of intimate and nonintimate partner violence among a sample of
      249 HIV-positive women in Kazakhstan. We found high prevalence of both lifetime
      intimate partner violence (52%) and nonintimate partner violence (30%). Together,
      nearly 60% experienced at least one incident of violence by either an intimate or
      nonintimate partner (gender-based violence [GBV]). In the multivariate analyses,
      we found associations between several individual, interpersonal, and socio
      structural risk factors and GBV. Findings provide direction for practice, policy,
      and future research to address the intersection of GBV and HIV in Kazakhstan.

PMID- 29332522
TI  - I Said No: The Impact of Voicing Non-Consent on Women's Perceptions of and
      Responses to Rape.
AB  - The current study explored the impact of voicing non-consent in relation to rape.
      Aims of the study included determining (a) the prevalence of voicing non-consent,
      (b) the relationship of voicing non-consent to verbal and physical resistance,
      and (c) whether voicing non-consent predicts distress and rape acknowledgment.
      Out of 262 college women who experienced rape, 81% voiced non-consent. Voicing
      non-consent was related to verbal and physical resistance, but was distinct in
      prevalence and prediction of distress. Voicing non-consent was associated with
      trauma-related symptoms in multivariate models. Women who voiced non-consent were
      more likely to acknowledge their experience as rape or sexual assault.
      Implications are discussed.

PMID- 29332521
TI  - A Template Analysis of Intimate Partner Violence Survivors' Experiences of Animal
      Maltreatment: Implications for Safety Planning and Intervention.
AB  - This study explores the intersection of intimate partner violence (IPV) and
      animal cruelty in an ethnically diverse sample of 103 pet-owning IPV survivors
      recruited from community-based domestic violence programs. Template analysis
      revealed five themes: (a) Animal Maltreatment by Partner as a Tactic of Coercive
      Power and Control, (b) Animal Maltreatment by Partner as Discipline or Punishment
      of Pet, (c) Animal Maltreatment by Children, (d) Emotional and Psychological
      Impact of Animal Maltreatment Exposure, and (e) Pets as an Obstacle to Effective
      Safety Planning. Results demonstrate the potential impact of animal maltreatment
      exposure on women and child IPV survivors' health and safety.

PMID- 29332523
TI  - Challenging Narratives of the Anti-Rape Movement's Decline.
AB  - A recent trend in scholarship characterizes the anti-rape movement as founded
      with radical goals and achieving success at reforming rape laws, but then
      declining because of co-optation by the state. This article challenges narratives
      of decline in light of the history of the anti-rape movement and current anti
      rape activism. By focusing their critique on criminal justice and therapeutic
      approaches to sexual violence, and failing to account for the diversity of the
      anti-rape movement, advocates for narratives of decline ignore parts of the
      movement that challenge the state and other parts that use broader cultural and
      community-based strategies to end rape.

PMID- 29332524
TI  - Exploring the Moderating Role of Problematic Substance Use in the Relations
      Between Borderline and Antisocial Personality Features and Intimate Partner
      Violence.
AB  - Borderline and antisocial personality features relate to multiple externalizing
      behaviors, including intimate partner violence (IPV). However, not all
      individuals with borderline and antisocial traits perpetrate IPV. The strength of
      the personality-IPV link may be related to problematic substance use. We examined
      borderline and antisocial personality features, problematic substance use, and
      IPV in a community sample of couples. Positive relations between both borderline
      and antisocial features and IPV were stronger in conditions of high problematic
      alcohol use relative to low problematic alcohol use. Alcohol misuse may be an
      important factor to consider for IPV reduction in men with these personality
      features.

PMID- 29332525
TI  - Bar Training for Active Bystanders: Evaluation of a Community-Based Bystander
      Intervention Program.
AB  - Bystander intervention programs are proliferating on college campuses and are
      slowly gaining momentum as sexual violence prevention programs suitable for the
      larger community. In particular, bystander intervention programs aimed at bar
      staff have been developed in a number of locations. This study entails the
      exploratory evaluation of a community-based bystander program for bar staff.
      Using a pre-posttest design, this study suggests that evidence surrounding the
      effectiveness of this program is promising as it decreases rape myths, decreases
      barriers to intervention, and increases bartenders willingness to intervene.
      Future research and policy implications are discussed.

PMID- 29332526
TI  - The Effects of Victim Age, Perceiver Gender, and Parental Status on Perceptions
      of Victim Culpability When Girls or Women Are Sexually Abused.
AB  - This study investigated perceptions of victim culpability in sexual assaults
      against girls and women according to victim age, perceiver gender, and perceiver
      parental status. Overall, 420 jury-eligible participants completed an online
      survey recording their attributions of guilt, responsibility, and blame toward 10
      , 15-, and 20-year-old girls and women in relation to sexual assault.
      Attributions of culpability were affected by whether the victim physically or
      verbally resisted the abuse, wore sexually revealing clothes, or was described as
      having acted promiscuously. Fifteen-year-old victims were perceived as more
      culpable for the abuse than 10-year-old victims. Implications of these findings
      are discussed.

PMID- 29332527
TI  - Domestic Violence Counseling in Rural Northern China: Gender, Social Harmony, and
      Human Rights.
AB  - Domestic violence (DV) affects over a third of Chinese women in a relationship.
      Focusing on ethnographic data from six staff members and six DV survivors at a
      rural, state-affiliated women's center in China in 2010, this article relies on
      Henrietta Moore's notion of the poststructuralist gendered subject to examine how
      the staff draw on discourses about gender and social harmony in persuading women
      to stay in their marriages, rather than on human rights discourses that emphasize
      survivor safety. It shows that DV survivors are frequently sent back to dangerous
      homes where their health is placed at risk.

PMID- 29332528
TI  - "Killed Out of Love": A Frame Analysis of Domestic Violence Coverage in Hong
      Kong.
AB  - A frame analysis was conducted on a Hong Kong newspaper to determine whether news
      coverage of female fatalities at the hands of their intimate partners was
      reported in conventional domestic violence ways or if there were culture-specific
      explanations. Overall, most coverage supported known views of domestic violence,
      justifying the perpetrator and categorizing the issue as isolated crime. However,
      a few stories highlighted the historical subordination of women under patriarchy
      in Confucianism as an important cultural factor. Findings have implications for
      the lack of generalization of the social problem, and the understanding of
      cultural and political power in Hong Kong society.

PMID- 29332529
TI  - Alcohol-Related Victim Behavior and Rape Myth Acceptance as Predictors of Victim
      Blame in Sexual Assault Cases.
AB  - Two studies analyzed the influence of victim behavior, drink type, and observer
      rape myth acceptance (RMA) on attributions of blame to victims of sexual assault.
      In Study 1, people higher in RMA blamed the victim more when she accepted rather
      than rejected the aggressor's invitation to buy her a drink. In Study 2, we
      analyzed if the effects depended on who offered the invitation for a drink (a
      friend or aggressor). RMA was more closely related to victim blame when she
      accepted (vs. rejected) the offer of a drink from the aggressor. In both studies,
      drink type (alcoholic vs. nonalcoholic) did not interact with the other
      variables.

PMID- 29332530
TI  - Reconciliation of patient/doctor vocabulary in a structured resource.
AB  - Today, social media is increasingly used by patients to openly discuss their
      health. Mining automatically such data is a challenging task because of the non
      structured nature of the text and the use of many abbreviations and the slang
      terms. Our goal is to use Patient Authored Text to build a French Consumer Health
      Vocabulary on breast cancer field, by collecting various kinds of non-experts'
      expressions that are related to their diseases and then compare them to
      biomedical terms used by health care professionals. We combine several methods of
      the literature based on linguistic and statistical approaches to extract
      candidate terms used by non-experts and to link them to expert terms. We use
      messages extracted from the forum on ' cancerdusein.org ' and a vocabulary
      dedicated to breast cancer elaborated by the Institut National Du Cancer. We have
      built an efficient vocabulary composed of 192 validated relationships and
      formalized in Simple Knowledge Organization System ontology.

PMID- 29332531
TI  - Supporting Rape Survivors Through the Criminal Injuries Compensation Scheme: An
      Exploration of English and Welsh Independent Sexual Violence Advisors'
      Experiences.
AB  - English and Welsh responses to rape have long been critically examined, leading
      to attempted improvements in the criminal justice system. Despite this, little
      attention has been paid to the Criminal Injuries Compensation Scheme (CICS) and
      the difficulties applying it to rape. To begin addressing this gap, researchers
      interviewed three, and qualitatively surveyed 22, Independent Sexual Violence
      Advisors. The findings suggest that CICS may not only reinforce rape myths and
      disadvantage vulnerable survivors, but is also a source of validation and
      contributes to survivor justice. The study, while exploratory, therefore,
      highlights the need for further discussion about rape survivor compensation.

PMID- 29332532
TI  - Is the End Really the End? Prevalence and Correlates of College Women's
      Intentions to Return to an Abusive Relationship.
AB  - Fifty-six college women completed surveys before and after terminating an
      abusive, heterosexual dating relationship. Whereas 64% of women had contact with
      their abusive partner post break-up, only 14% reported a moderate to high
      likelihood that they would return. Intentions to return were prospectively
      predicted by fewer perceived quality of alternatives, and cross-sectional
      correlates of intentions to return were being single, shorter time since
      relationship termination, having contact with one's abusive ex-partner, and
      social pressure to return. These data can be used to inform intervention and
      advocacy efforts and to guide future research.

PMID- 29332533
TI  - Assessing the Impact of a Focused Deterrence Strategy to Combat Intimate Partner
      Domestic Violence.
AB  - The Offender Focused Domestic Violence Initiative (OFDVI) represents for the
      first time anywhere the application of the evidence-based focused deterrence
      policing approach to combat intimate partner domestic violence (IPDV). Through
      holding offenders accountable, the strategy has resulted in 20% reductions each
      in IPDV-related calls for police service and arrests. Victim injuries have been
      significantly reduced and the 1-year IPDV offender recidivism rate is about 16
      17%. The backbone of the OFDVI strategy is the multidisciplinary collaboration of
      law enforcement and community partners which has resulted in identification and
      resolving system issues which have historically allowed offenders to repeat IPDV
      without consequence.

PMID- 29332534
TI  - Mediated Effects of Coping on Mental Health Outcomes of African American Women
      Exposed to Physical and Psychological Abuse.
AB  - Few studies have assessed the individual symptoms of posttraumatic stress
      disorder (PTSD) as separate mental health consequences of intimate partner abuse
      (IPA). This study examined the role of coping strategies associated with symptoms
      of PTSD in a community sample of African American women who have experienced
      abuse ( N = 128). The results revealed that nonphysical abuse was more prevalent
      than physical abuse. Specific symptoms of PTSD expressed depended on the type of
      abuse experienced and the type of coping strategies utilized. The findings have
      multiple implications on how IPA is studied as well as its clinical screening and
      treatment processes.

PMID- 29332535
TI  - Viewing Gendered Violence in Guatemala Through Photovoice.
AB  - This research examined rural and urban women's experiences of gender-based
      violence in Chimaltenango, Guatemala. Photovoice methodology was used to describe
      and analyze local realities and vulnerabilities, and ethnographic techniques
      added cultural and contextual factors. While the initial focus was on intimate
      partner violence, results showed that violence for women exists from childhood to
      senior years. Participants noted gaps in services and participated in a public
      strategy workshop to address these. Challenges and opportunities are presented
      around the enduring and complex global crisis of gendered violence. Photovoice is
      a powerful method for organizations to better understand and respond to local
      issues.

PMID- 29332536
TI  - The Rise of the Crime Victim and Punitive Policies? Changes to the Legal
      Regulation of Intimate Partner Violence in Finland.
AB  - This article examines intimate partnership violence as a question of criminal
      justice policy in Finland, and contributes to criminological discussions
      regarding oft-stated connections between the politicization of the victim, the
      treatment of offenders, and repressive criminal justice policies. In this
      discussion, legislation aiming to regulate and prevent violence against women has
      often been utilized as an example of such punitive policies. Although criminal
      policies in Nordic countries differ significantly from more punitive Anglophone
      policies, punitive tendencies, it has been argued, have increased in the former,
      too. This article analyzes the change in legal regulations and the criminal
      political status of intimate partner violence in Finland between 1990 and 2004,
      while examining the juxtaposition of victims and offenders alongside repressive
      demands.

PMID- 29332537
TI  - AZD9291 Increases Sensitivity to Radiation in PC-9-IR Cells by Delaying DNA
      Damage Repair after Irradiation and Inducing Apoptosis.
AB  - AZD9291 is a novel, irreversible epidermal growth factor receptor (EGFR) tyrosine
      kinase inhibitor (TKI), which is administered orally. It has been proven
      effective in non-small cell lung cancer (NSCLC) patients, with both EGFR
      sensitizing and EGFR T790M mutations in preclinical models. However, the
      potential therapeutic effects of AZD9291 combined with other modalities,
      including ionizing radiation, are not well understood. The presence of AZD9291
      significantly increases the cell-killing effects of radiation in PC-9-IR cells
      with a secondary EGFR mutation (T790M), which was developed from NSCLC PC-9 cells
      (human lung adenocarcinoma cell with EGFR 19 exon 15 bp deletion) after chronic
      exposure to increasing doses of gefitinib, and in H1975 cells (human lung
      adenocarcinoma cell with EGFR exon 20 T790M mutation de novo), but not in PC-9
      cells or in H460 cells (human lung adenocarcinoma cell with wild-type EGFR). In
      PC-9-IR cells, AZD9291 remarkably decreases phosphorylation levels of EGFR,
      extracellular regulated protein kinase (ERK), and protein kinase B (AKT). AZD9291
      increases sensitivity to radiation in PC-9-IR cells by delaying deoxyribonucleic
      acid (DNA) damage repair after irradiation and inducing apoptosis, and enhances
      tumor growth inhibition when combined with radiation in PC-9-IR xenografts. Our
      findings suggest a potential therapeutic effect of AZD9291 as a radiation
      sensitizer in lung cancer cells with an acquired EGFR T790M mutation, providing a
      rationale for a clinical trial using the combination of AZD9291 and radiation in
      NSCLCs harboring acquired T790M mutation.

PMID- 29332539
TI  - Whole-Body Oxygen (16O) Ion-Exposure-Induced Impairments in Social Odor
      Recognition Memory in Rats are Dose and Time Dependent.
AB  - Future long-duration space missions will involve travel outside of the Earth's
      magnetosphere, which will result in increased radiation exposure for astronauts.
      Exposure could permanently damage multiple tissues, including the central nervous
      system (CNS), and result in deleterious effects on cognition and behavior during
      and beyond the mission. Here, we assessed the effects of whole-body oxygen ion
      (16O; 1,000 MeV/n) exposure (5 or 25 cGy) on social odor recognition memory in
      male Long-Evans rats at one and six months after exposure. At one month
      postirradiation, all rats displayed a preference for a novel 1 (N1) social odor
      experienced during the habituation phase. When assessed for recognition memory 24
      h later, only sham-irradiated rats spent more time exploring a second novel
      social odor (novel 2, N2), whereas rats irradiated with 5 or 25 cGy 16O ions did
      not show a preference for the N2 odor compared to the N1 odor experienced 24 h
      earlier, thus displaying a memory deficit for recall of the social odor
      encountered 24 h prior. At six months postirradiation, rats exposed to 25 cGy
      showed persistent deficits in 24 h recognition memory, while the 5 cGy-exposed
      rats did not. Thus, 24 h recognition memory was apparently recovered at six
      months postirradiation for the low, but not the higher, dose of 16O ions. Both
      irradiated groups displayed similar numbers of Ki67+ cells, a marker of cell
      proliferation, in the subventricular zone. These results further demonstrate that
      space-relevant 16O ion exposure has deleterious effects on the CNS, which are
      related to both radiation dose and time after exposure.

PMID- 29332540
TI  - Using the Woman Abuse Screening Tool to Screen for and Assess Dating Violence in
      College Students.
AB  - The study aimed to evaluate the measurement properties of the Woman Abuse
      Screening Tool (WAST) in Chinese college students. A cross-sectional survey was
      conducted in Hong Kong. A cutoff score of 10 was found to be able to discriminate
      between abused and nonabused Chinese young adults. The total score was
      significantly correlated with total scores for anxiety and depression on the
      Chinese version of the Hospital Anxiety and Depression Scale. Two-factor
      structure of the WAST was supported by exploratory and confirmatory factor
      analyses. The Chinese WAST was found to be valid in screening for and assessing
      intimate partner violence.

PMID- 29332541
TI  - After the Escape: Physical Abuse of Offspring, Posttraumatic Stress Disorder, and
      the Legacy of Political Violence in the DPRK.
AB  - What is the relationship between victimization by political violence against
      women in North Korea and later physical abuse of offspring? This article examines
      the relationships between victimization by political violence, posttraumatic
      stress disorder (PTSD), alcohol abuse/dependence, and abuse of offspring after
      arrival in South Korea. A random sample of 204 female North Korean defectors was
      used to test hypotheses. An oral history conducted with a survivor of North
      Korean political violence is provided in an appendix to contextualize the
      results. Analyses established a significant link between previous victimization
      by political violence and abuse of offspring but not mediation by either PTSD or
      alcohol abuse/dependence.

PMID- 29332542
TI  - Long Journeys Toward Freedom: The Relationship Between Coercive Control and Space
      for Action-Measurement and Emerging Evidence.
AB  - We report on the development of, and findings from, two scales measuring coercive
      control and space for action over a period of 3 years in a sample of 100 women
      who had accessed domestic violence services. We present statistical evidence to
      show a significant correlation between coercive control and space for action.
      However, dealing with violence is not a linear process, and support needs to
      extend beyond being enabled to separate. The scales advance measurement of
      women's experience of coercive control and, through the space for action scale,
      document their ability to restore agency and freedom in contexts of relative
      safety.

PMID- 29332538
TI  - Role of Infiltrating Monocytes in the Development of Radiation-Induced Pulmonary
      Fibrosis.
AB  - Lung exposure to radiation induces an injury response that includes the release
      of cytokines and chemotactic mediators; these signals recruit immune cells to
      execute inflammatory and wound-healing processes. However, radiation alters the
      pulmonary microenvironment, dysregulating the immune responses and preventing a
      return to homeostasis. Importantly, dysregulation is observed as a chronic
      inflammation, which can progress into pneumonitis and promote pulmonary fibrosis;
      inflammatory monocytes, which are bone marrow derived and express CCR2, have been
      shown to migrate into the lung after radiation exposure. Although the extent to
      which recruited inflammatory monocytes contribute to radiation-induced pulmonary
      fibrosis has not been fully investigated, we hypothesize that its pathogenesis is
      reliant on this population. The CC chemokine ligand, CCL2, is a chemotactic
      mediator responsible for trafficking of CCR2+ inflammatory cells into the lung.
      Therefore, the contribution of this mediator to fibrosis development was
      analyzed. Interleukin (IL)-1beta, a potent pro-inflammatory cytokine expressed
      during the radiation response, and its receptor, IL-1R1, were also evaluated. To
      this end, CCR2-/-, IL-1beta-/- and IL-1R1-/- chimeric mice were generated and
      exposed to 12.5 Gy thoracic radiation, and their response was compared to wild
      type (C57BL/6) syngeneic controls. Fibrotic foci were observed in the periphery
      of the lungs of C57 syngeneic mice and CCR2-/- recipient mice that received C57
      bone marrow (C57 > CCR2-/-) by 16 and 12 weeks after irradiation, respectively.
      In contrast, in the mice that had received bone marrow lacking CCR2 (CCR2-/- >
      C57 and CCR2-/- syngeneic mice), no pulmonary fibrosis was observed at 22 weeks
      postirradiation. This observation correlated with decreased numbers of
      infiltrating and interstitial macrophages compared to controls, as well as
      reduced proportions of pro-inflammatory Ly6C+ macrophages observed at 12-18 weeks
      postirradiation, suggesting that CCR2+ macrophages contribute to radiation
      induced pulmonary fibrosis. Interestingly, reduced proportions of CD206+ lung
      macrophages were also present at these time points in CCR2-/- chimeric mice,
      regardless of donor bone marrow type, suggesting that the phenotype of resident
      subsets may be influenced by CCR2. Furthermore, chimeras, in which either IL
      1beta was ablated from infiltrating cells or IL-1R1 from lung tissues, were also
      protected from fibrosis development, correlating with attenuated CCL2 production;
      these data suggest that IL-1beta may influence chemotactic signaling after
      irradiation. Overall, our data suggest that CCR2+ infiltrating monocyte-derived
      macrophages may play a critical role in the development of radiation-induced
      pulmonary fibrosis.

PMID- 29332543
TI  - Difficult but Close Relationships: Children's Perspectives on Relationships With
      Their Mothers in the Context of Domestic Violence.
AB  - This article reports findings from a participative and qualitative study
      conducted with children who had experienced domestic violence, focusing on their
      perspectives on their relationships with their mothers. Three focus groups and 46
      individual interviews were conducted with children to gather their experiences.
      The research findings demonstrate that women's and children's victimizations are
      inextricably linked, and that domestic violence affects mother-child
      relationships. They also show that, despite the challenges and difficulties,
      children generally consider their mothers as very significant individuals in
      their lives, and have close relationships with them. The findings also reveal a
      dynamic of mutual protectiveness.

PMID- 29332544
TI  - The Possible Use of Preoperative Natriuretic Peptides for Discriminating Low
      Versus Moderate-High Surgical Risk Patient.
AB  - Perioperative risk scores for patients undergoing noncardiac surgery are
      generally considered inaccurate, poor, or, at best, modest. We propose estimating
      a patient's pretest and posttest probability of cardiac morbidity and death using
      the preoperative scoring system plus the negative likelihood ratio from brain
      natriuretic peptide (BNP) or N-terminal proB-type natriuretic peptide (NT-proBNP)
      plasma levels. Our clinical challenge scenario showed a pretest probability of
      postoperative major cardiac complications with the patient risk factor as 6.6%
      for the Revised Cardiac Risk Index and between 1% and 5% (intermediate risk) per
      the recent European Society of Cardiology and the European Society of
      Anesthesiologist guidelines for surgical risk estimation. In fact, the American
      College of Cardiology and the American Heart Association guidelines consider the
      same surgical procedure for elevated risk. The posttest probability takes
      advantage of a negative likelihood ratio from BNP plasma levels, with patient
      risk factor reduced to 0.8% and surgical risk to 1.1%. In the same way, the
      pretest American College of Surgeons National Surgical Quality Improvement
      Program score decreased from 18.8% to 3.5% for severe complications and from 0.9%
      to 0.1% for death at <=90 days. Following noncardiac surgery, postoperative
      complications and mortality are often cardiac in nature. The negative likelihood
      ratio of BNP and NT-proBNP plasma levels provides a quick, low-cost tool for
      recognizing and reclassifying the cardiovascular risk of those undergoing
      noncardiac surgery, thereby singling out low- versus moderate-high-risk surgical
      patients.

PMID- 29332546
TI  - Drinking Motives as a Moderator of the Relationship Between Dating Violence
      Victimization and Alcohol Problems.
AB  - The present study sought to examine whether drinking motives (i.e., coping,
      social, conformity, and enhancement) moderated the relationship between physical,
      sexual, and psychological dating violence victimization and alcohol-related
      problems in a sample of drinking college women ( N = 177). Results demonstrated
      that coping and social drinking motives moderated the relationship between sexual
      victimization and alcohol problems; conformity, social, and enhancement drinking
      motives moderated the relationship between alcohol-related problems and physical
      victimization; no significant findings were evident for psychological aggression
      victimization. Our results partially support the self-medication model of alcohol
      use, and this may be particularly relevant to sexual victimization.

PMID- 29332545
TI  - Long Noncoding RNA H19 Inhibits Cell Viability, Migration, and Invasion Via
      Downregulation of IRS-1 in Thyroid Cancer Cells.
AB  - Thyroid cancer is a common endocrine gland malignancy which exhibited rapid
      increased incidence worldwide in recent decades. This study was aimed to
      investigate the role of long noncoding RNA H19 in thyroid cancer. Long noncoding
      RNA H19 was overexpressed or knockdown in thyroid cancer cells SW579 and TPC-1,
      and the expression of long noncoding RNA H19 was detected by real-time polymerase
      chain reaction. The cell viability, migration, and invasion were determined by 3
      (4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide assay,
      Transwell assay, and wound healing assay, respectively. Furthermore, cell
      apoptosis was analyzed by flow cytometry, and expressions of some factors that
      were related to phosphatidyl inositide 3-kinases/protein kinase B and nuclear
      factor kappaB signal pathway were measured by Western blotting. This study
      revealed that cell viability and migration/invasion of SW579 and TPC-1 were
      significantly decreased by long noncoding RNA H19 overexpression compared with
      the control group ( P < .05), whereas cell apoptosis was statistically increased
      ( P < .001). Meanwhile, cell viability and migration/invasion were significantly
      increased after long noncoding RNA H19 knockdown ( P < .05). Furthermore, long
      noncoding RNA H19 negatively regulated the expression of insulin receptor
      substrate 1 and thus effect on cell proliferation and apoptosis. Insulin receptor
      substrate 1 regulated the activation of phosphatidyl inositide 3-kinases/AKT and
      nuclear factor kappaB signal pathways. In conclusion, long noncoding RNA H19
      could suppress cell viability, migration, and invasion via downregulation of
      insulin receptor substrate 1 in SW579 and TPC-1 cells. These results suggested
      the important role of long noncoding RNA H19 in thyroid cancer, and long
      noncoding RNA H19 might be a potential target of thyroid cancer treatment.

PMID- 29332547
TI  - The Psychology of the Politics of Rape: Political Ideology, Moral Foundations,
      and Attitudes Toward Rape.
AB  - Previous research has found that conservatives and liberals emphasize different
      moral foundations. The purpose of these two studies was to investigate whether
      moral foundations mediate the relationship between political ideology and
      attitudes toward rape among U.S. college students. In Study 1, moral foundations
      fully mediated the relationship between political ideology and rape myth
      acceptance. Study 2 generally replicated the results of Study 1, with binding
      foundations demonstrating the most consistent mediating effects. These results
      suggest that individual differences in moral decision-making may explain the
      relationship between political ideology and attitudes toward rape.

PMID- 29332548
TI  - Sociodemographic and Incident Variables as Predictors of Victim Injury From
      Intimate Partner Violence: Findings From Police Reports.
AB  - Predictors of victim injury from intimate partner violence (IPV) were
      investigated using 1,292 police reports collected in South Carolina in 2009/2010.
      All cases were opposite sex adults. Results from bivariate statistics showed that
      IPV cases with ( n = 649) and without visible injuries ( n = 643) differed on
      victim gender, victim race, type of relationship, and perpetrator's alcohol use.
      Results from a logistic regression analysis predicting victim injury showed
      higher odds ratios for males, Whites, and couples identified as cohabitants.
      Although most victims, including most injured victims, were Black women, males
      and Whites were overrepresented in the injured group.

PMID- 29332549
TI  - The Role of Sexual Abuse in Trauma Symptoms, Delinquent and Suicidal Behaviors,
      and Criminal Justice Outcomes Among Females in a Juvenile Justice Diversion
      Program.
AB  - Female juvenile justice-involved (JJI) youth experience more sexual abuse (SA)
      than their non-JJI counterparts or their male JJI counterparts. This study
      examines SA's role among JJI females ( N = 1,307) in a behavioral health
      diversion program. Results indicate that SA increases the risk of psychological
      trauma, particularly posttraumatic stress and depression. SA also increases the
      odds of suicidal behavior, running away, and substance use. SA females have the
      same odds of successfully completing behavioral health diversion and being
      charged with any offense or misdemeanor after termination as non-SA females.
      Implications of research and future directions are discussed.

PMID- 29332550
TI  - How Ending Impunity for Conflict-Related Sexual Violence Overwhelmed the UN
      Women, Peace, and Security Agenda: A Discursive Genealogy.
AB  - The recent unprecedented focus on ending impunity for conflict-related sexual
      violence (CRSV) is positive in many respects. However, it has narrowed the scope
      of Security Council Resolution 1325 and the women, peace, and security (WPS)
      agenda it established in 2000. Through a critical discursive genealogy of the
      interrelation of two UN agendas-protection of civilians in armed conflict and
      women, peace, and security-the author traces how CRSV emerged as the defining
      issue of the latter while the transformative imperative of making women's
      participation central to every UN endeavor for peace and security has failed to
      gain traction.

PMID- 29332551
TI  - How Narratives of Fear Shape Girls' Participation in Community Life in Two
      Conflict-Affected Populations.
AB  - Numerous social factors shape girls' lives in conflict-affected settings,
      affecting their vulnerability to gender-based violence (GBV). Qualitative
      research methods were used to examine spaces of perceived safety and risk for
      girls living in two conflict-affected populations: camps in Ethiopia hosting
      primarily South Sudanese and Sudanese refugees and communities in eastern
      Democratic Republic of Congo. Three major themes emerged: (a) challenges around
      caregiver-child communication regarding development, sex, and sexual violence;
      (b) a typology of safe/risky spaces; and (c) the influence of male-dominated
      spaces on experiences and fear of GBV. The findings have implications for
      programs focused on reducing adolescent girls' vulnerability to violence within
      conflict-affected contexts.

PMID- 29332553
TI  - Understanding Trauma Normativeness, Normalization, and Help Seeking in Homeless
      Mothers.
AB  - Although trauma-informed approaches guide services to families experiencing
      homelessness, more emphasis is placed on securing housing than addressing
      underlying trauma contributing to housing instability. Examining the stories of
      29 homeless and/or unstably housed mothers within the broader literature on
      family trauma and violence, chronic illness, and cultural aspects of family
      functioning, we define the process of trauma normativeness and normalization that
      may occur with repeated trauma experiences and argue that rehousing efforts must
      include concomitant attention to trauma and to understanding how individual,
      family, community, and cultural factors influence help-seeking behaviors in this
      vulnerable and growing population.

PMID- 29332554
TI  - Evaluating the dose-dependent mechanism of action of trazodone by estimation of
      occupancies for different brain neurotransmitter targets.
AB  - Trazodone is a drug that was introduced in the clinic almost 40 years ago. It is
      licensed to treat depression, but it is also commonly used off-label to treat
      insomnia. A recent study shows that it could be promising in preventing
      neurodegeneration in mice, and clinical trials to assess its possible beneficial
      effects on dementia and Alzheimer's disease are expected to start soon in humans.
      In this study, we describe the dose-dependent pharmacology of trazodone by
      carrying out pharmacokinetic simulations aiming to predict the brain
      concentrations of trazodone for different drug-dosing regimens and calculating
      occupancy for 28 different targets for which published trazodone-binding data are
      available. Our study indicates that low doses of trazodone (typically 50 mg
      daily) should suffice to block specific receptors responsible for the hypnotic
      effect, and to provide the protective effect against neuroinflammation and
      neurodegeneration that could be beneficial in dementia. Higher doses are required
      for an antidepressant effect. The occupancy of specific receptors at therapeutic
      doses also explains peculiar side effects reported by patients treated with
      trazodone (e.g. dry-mouth, hypotension and priapism).

PMID- 29332552
TI  - Practitioner Views on the Impacts, Challenges, and Barriers in Supporting Older
      Survivors of Sexual Violence.
AB  - Despite half a century of research on both sexual violence and elder abuse, the
      intersection between the two remains largely unexplored. Using theoretical lenses
      of feminist criminology and critical feminist gerontology, this article explores
      the intersection between age and sexual violence drawing on interviews with 23
      practitioners supporting older survivors (aged 60 and over). They reported
      physical and emotional effects of sexual violence leading to limited lifestyles,
      disengagement from social networks, and reliance on pathogenic coping strategies.
      Provision of effective support was complicated by challenges associated with
      aging bodies and the social stigma associated with both sexual victimhood and
      older age. Additional challenges lay in supporting older male survivors and those
      living with dementia. The article ends by discussing implications for practice
      and an agenda for future research.

PMID- 29332555
TI  - Victim Empowerment, Safety, and Perpetrator Accountability Through Collaboration:
      A Crisis to Transformation Conceptual Model.
AB  - This article describes the development of the Victim Empowerment, Safety, and
      Perpetrator Accountability through Collaboration (VESPAC) model based on a
      grounded theory analysis of congressionally mandated and permissible purpose
      areas for grants authorized by the Violence Against Women Act. These areas are
      reflective of ongoing and emerging needs of victims and agencies serving victims
      and are rooted in the expertise, insight, and concerns of those who work most
      closely with victims and perpetrators on a regular basis. Analysis resulted in
      five overarching and interconnected themes: Community Readiness, Victim Services,
      Justice Responses, Coordinated Community Responses, and Cultural Relevance. The
      final model emphasizes the centrality of coordinated community responses to
      ensure that the remaining components of the model work in tandem across time to
      achieve victim safety and perpetrator accountability in a culturally appropriate
      way. The model also may help agencies, coalitions, and communities think "big"
      and consider more strategically about where their strengths best fit in the vast
      scope of victim needs necessary to meet safety goals and where they might benefit
      most from the expertise of partners.

PMID- 29332556
TI  - "Back Off Buddy, This Is My Body, Not Yours": Empowering Girls Through Self
      Defense.
AB  - Although growing recognition is being given to the benefits of teaching self
      defense skills to college women, very little research attention has considered
      the impacts of providing such courses to school-aged girls. This article presents
      the findings from a large-scale evaluation of self-defense programs provided to
      three different age groups of schoolgirls from diverse backgrounds in New
      Zealand, drawing on survey responses from the girls themselves, supplemented by
      qualitative data provided by key informant interviews with their school and self
      defense teachers. The findings provide clear evidence of the many positive
      benefits that can result for girls of all ages who participate in feminist self
      defense courses taught by carefully trained instructors with a strong empowerment
      focus.

PMID- 29332558
TI  - Situational Variations in, and Women's Accounts of, Avoided Acts of Serious
      Intimate Partner Violence.
AB  - This study explores how both situations and persons contribute to the probability
      that a serious incident of intimate partner violence (IPV) can be avoided. Data,
      on both completed and avoided acts of serious partner violence, were collected
      from jailed women in Baltimore. Factors that increase the odds of avoiding a
      serious incident of IPV are a woman's age, her partner's initiation of a
      threat/attack, and being accompanied by a family member. Factors that decrease
      the odds of avoided serious violence include an indicator of what the dispute was
      about, her partner's substance abuse, prior experiences with avoided acts of
      violence, and lifetime arrests.

PMID- 29332557
TI  - Evaluation of a Victim-Centered, Trauma-Informed Victim Notification Protocol for
      Untested Sexual Assault Kits (SAKs).
AB  - Throughout the United States, hundreds of thousands of sexual assault kits (SAKs)
      have not been submitted by the police for forensic DNA testing, which raises
      complex issues regarding how victims ought to be notified about what happened to
      their kits. In this project, we evaluated a victim-centered, trauma-informed
      victim notification protocol that was implemented in Detroit, Michigan. Most
      victims (84%) did not have a strong negative emotional reaction to notification,
      and most (57%) decided to reengage with the criminal justice system. Victims of
      nonstranger sexual assaults were less likely to reengage postnotification
      compared with victims of stranger rape.

PMID- 29332559
TI  - The Relationship Between Domestic Partner Violence and Suicidal Behaviors in an
      Adult Community Sample: Examining Hope Agency and Pathways as Protective Factors.
AB  - We examined an additive and interactive model involving domestic partner violence
      (DPV) and hope in accounting for suicidal behaviors in a sample of 98 community
      adults. Results showed that DPV accounted for a significant amount of variance in
      suicidal behaviors. Hope further augmented the prediction model and accounted for
      suicidal behaviors beyond DPV. Finally, we found that DPV significantly
      interacted with both dimensions of hope to further account for additional
      variance in suicidal behaviors above and beyond the independent effects of DPV
      and hope. Implications for the role of hope in the relationship between DPV and
      suicidal behaviors are discussed.

PMID- 29332561
TI  - Editorial.

PMID- 29332560
TI  - Social Reactions to Sexual Assault Disclosure: A Qualitative Study of Informal
      Support Dyads.
AB  - This interview study examined 45 informal support dyads where sexual assault was
      disclosed. Analysis showed social reactions and appraisals of reactions varied by
      relationship type (family, friend, significant other). Themes identified were
      role reversal or "parentification" of supporters, reactions of anger and
      aggression toward perpetrators, supporters using their own trauma experiences to
      respond to survivors, and reactions of betrayal. Results revealed the potential
      for identifying relational patterns and dynamics occurring in social reactions
      through dyadic analysis not otherwise captured by a survivor-only perspective.
      This approach helps understand and address distinct relationship contexts to
      improve supporters' reactions to sexual assault disclosure.

PMID- 29332562
TI  - The Delicate Balance between the Good and the Bad IL-1 Proinflammatory Effects in
      Endometriosis.
AB  - BACKGROUND: Endometriosis is an inflammatory gynaecological disease with an
      associated chronic inflammation. Interleukin(IL)-1 is one of the most important
      immune and proinflammatory factors, produced mainly by monocytes and macrophages.
      Studies indicate the role of the cytokine from IL-1 family in endometrium-related
      disorders, particularly in endometriosis. METHODS: The information about the
      impact of cytokine from IL-1 cytokine family on the pathogenesis and development
      of endometriosis was obtained with an electronic literature search based on the
      PubMed and Medline databases, spanning the period of January 1950 to July 2017
      and includes associated references in the published studies. RESULTS: The
      impairment of the IL-1 family cytokine-network may lead to changes in the
      activation of immune system in the peritoneal cavity of women with endometriosis.
      The aberrant ectopic endometrial cell properties of adhesion, implantation and
      proliferation may be the result of a reduced suppressive capacity controlling the
      IL-1. The imbalance between IL-1alpha, pro-IL-1beta, mature IL-1beta and sIL-1R2
      and sIL-1RAcP in the peritoneal fluid and serum of women with endometriosis may
      be linked to the ability of transforming an acute inflammation into a chronic
      one. Despite the fact that peritoneal macrophages secrete more antiinflammatory
      IL-1Ra and less proinflammatory IL-1 in the peritoneal cavity in affected women,
      the inflammation still develops. CONCLUSIONS: This observation clearly suggested
      a significant inadequacy in the specific regulatory mechanisms of IL-1 activity
      at the peritoneal cavity level. The imbalance between all studied cytokines in
      endometriosis may escalate peritoneal inflammation and, in consequence, develop
      endometriosis.

PMID- 29332563
TI  - Multi-Target Directed Drugs as a Modern Approach for Drug Design Towards
      Alzheimer's Disease: An Update.
AB  - Alzheimer's disease (AD) is a progressive multifactorial neurodegenerative
      disorder. Currently, no effective treatment is available and this is due to
      multiple factors involved in pathophysiology and severity of AD. A recent
      approach for the rational design of new drug candidates, also called multitarget
      directed ligands (MTDL) strategy, has been used to develop a variety of hybrid
      compounds capable to act simultaneously in diverse biological targets. The
      discovery of drug candidates capable of targeting multiple factors involved in AD
      pathogenesis would greatly facilitate in improving therapeutic strategies. This
      review is a complement to another review article, recently published by our
      group, which covered the previous period of 2005-2012, and highlights recent
      advances and examples of the exploitation of MTDLs approach in the rational
      design of novel drug candidate prototypes for the treatment of AD.

PMID- 29332564
TI  - Mesenchymal Stem Cell Therapy in Intracerebral Haemorrhagic Stroke.
AB  - BACKGROUND: Spontaneous intracerebral haemorrhage (ICH) is a relatively common
      fatal disease, with an overall global incidence estimated at 24.6 per 100,000
      person- years. Given the high degree of morbidity and mortality associated with
      ICH, therapies that may have neuroprotective effects are of increasing interest
      to clinicians. In this last context, cell therapies offer the promise of
      improving the disease course which cannot be addressed adequately by existing
      treatments. OBJECTIVE: The aim of this review is to evaluate the protective
      effects and molecular mechanisms of mesenchymal stem cells (MSCs) on haemorrhagic
      brain following ICH. We also discuss possible emerging therapeutic approaches
      worth of further research. METHODS AND RESULTS: The available literature on the
      therapeutic potential of MSCs in ICH animal models clearly demonstrated that MSCs
      enhance the functional recovery and reduce the volume of the infarct size
      exerting anti-inflammatory and angiogenic properties. However, the quality of the
      original articles investigating the efficacy of stem cell therapies in ICH animal
      models is still poor and the lack of ICH clinical trial does not permit to reach
      any relevant conclusions. CONCLUSION: Further studies have to be implemented in
      order to achieve standardized methods of MSCs isolation, characterization and
      administration to improve ICH treatments with MSCs or MSC-derived products.

PMID- 29332566
TI  - Stimuli Responsive Nanoparticles for Controlled Anti-cancer Drug Release.
AB  - Conventional drugs used for cancer chemotherapy have severe toxic side effects
      and show individually varied therapeutic responses. The convergence of
      nanotechnology, biology, material science and pharmacy offers a perspective
      strategy for cancer chemotherapy. Nanoparticles loaded with anti-cancer drug have
      been designed to overcome the limitations associated with conventional drugs,
      several nanomedicines have been approved by FDA and shown good performances in
      clinical practice. However, the therapeutic efficacies cannot be enhanced. Taking
      this into account, stimuli responsive nanoparticles present the ability to
      enhance therapeutic efficacy and reduce side effects. In this review, we
      systematically summarized the recent progresses of controlled anti-cancer drug
      release systems based on nanoparticles with different stimuli response including
      pH, temperature, light, redox and others. If the achievements of the past can be
      extrapolated into the future, it is highly likely that responsive nanoparticles
      with a wide array of desirable properties can be eventually developed for safe
      and efficient cancer therapy.

PMID- 29332565
TI  - Beyond the "Lock and Key" Paradigm: Targeting Lipid Rafts to Induce the Selective
      Apoptosis of Cancer Cells.
AB  - For more than 40 years, the fluid mosaic model of cellular membranes has
      supported our vision of an inert lipid bilayer containing membrane protein
      receptors that are randomly hit by extracellular molecules to trigger
      intracellular signaling events. However, the notion that compartmentalized
      cholesterol- and sphingomyelin-rich membrane microdomains (known as lipid rafts)
      spatially arrange receptors and effectors to promote kinetically favorable
      interactions necessary for the signal transduction sounds much more realistic.
      Despite their assumed importance for the dynamics of ligand-receptor
      interactions, lipid rafts and biomembranes as a whole remain less explored than
      the other classes of biomolecules because of the higher variability and
      complexity of their membrane phases, which rarely provide the detailed atomic
      level structural data in X-ray crystallography assays necessary for molecular
      modeling studies. The fact that some alkylphospholipids (e.g. edelfosine: 1-O
      octadecyl-2-O-methyl-rac-glycero-3-phosphocholine) selectively induce the
      apoptotic death of cancer cells by recruiting Fas death receptors and the
      downstream signaling molecules into clusters of lipid rafts suggests these
      potential drug targets deserve a more in-depth investigation. Herein, we review
      the structure of lipid rafts, their role in apoptotic signaling pathways and
      their potential role as drug targets for the treatment of cancer.

PMID- 29332567
TI  - Nociceptin /Orphanin FQ Peptide (NOP) Receptor Modulators: An Update in Structure
      Activity Relationships.
AB  - Nociceptin /Orphanin FQ Peptide" receptor (NOPr) is a G-protein-coupled receptor
      with the nociceptin/orphanin FQ peptide (N/OFQ) as endogenous agonist. It is
      expressed in the nervous system as well as in some non-neural tissues. Its
      activation has pronociceptive effect at the supraspinal level, whereas at the
      spinal level it produces nociceptive effects at low doses and antinociceptive
      effects at higher doses. NOPr is also involved in mood and blood pressure
      regulation, immunoregulation, airway constriction, feeding, urination, bowel
      motility, learning and memory. Selective NOPr agonists have been tested
      clinically as anxiolytics and antitussives, and the antagonists as analgesics,
      antidepressants and in the treatment of alcohol addiction. Two NOPr radioligands
      have also been tested in humans as neuroimaging agents. Furthermore, the partial
      agonist peptide SER100 and N/OFQ have been used in clinical trials, respectively
      for congestive heart failure and overactive bladder. The evidence of interactions
      between NOP and MU-opioid receptor (MOPr) receptors has been exploited in the use
      of mixed NOPr/MOPr modulators as analgesics and in the treatment of drug
      addiction. These drugs are devoid of typical opioid liabilities. In this review,
      we outline the latest advances in the structure-activity relationships (SAR) of
      NOPr agonists and antagonists, with emphasis on affinity, activity, selectivity
      and pharmacokinetic features.

PMID- 29332568
TI  - FGF-21 as a Potential Biomarker for Mitochondrial Diseases.
AB  - The diagnosis of mitochondrial diseases is still challenging due to clinical and
      genetical heterogeneity. The development of advanced technologies including Whole
      Exome- Sequencing (WES) and Whole-Genome-Sequencing (WGS) has led to improvements
      in genetic diagnosis. However, a reliable biomarker in serum could enhance and
      ease the diagnosis and indeed reduce the need for muscle biopsy. Several studies
      suggest Fibroblast growth factor 21 (FGF-21) as a biomarker for diagnosis in
      mitochondrial disorders. It is known, that in patients with mitochondrial
      disorders, the expression of FGF-21 gets elevated in an effort to counteract the
      underlying metabolic deficiency. The growth and differentiation factor 15 (GDF
      15) has been described as a potential biomarker for mitochondrial diseases, too.
      In the present review, a literature research, using PubMed database about the
      reliability of FGF-21 as a biomarker for mitochondrial disorders and its
      comparison with GDF-15 has been performed.

PMID- 29332570
TI  - Proprotein Convertase Subtilisin/kexin type 9 Inhibition in Cardiovascular
      Prevention.
AB  - Elevated levels of Low Density Lipoprotein cholesterol (LDL-C) are directly
      associated with increased risk for atherosclerotic cardiovascular and
      cerebrovascular events. Statins have been used to control serum LDLC and this has
      translated into reduction in cardiovascular and cerebrovascular events. However,
      despite high dose statin therapy, LDL-C control may remain inadequate in some
      patients, particularly those with familial hypercholesterolemia. A new
      therapeutic approach has emerged in recent years with proprotein convertase
      subtilisin/kexin type 9 (PCSK9) inhibitors. In this review, we describe the
      development and the use of this new class of drugs.

PMID- 29332569
TI  - Cancer Treatment with Liposomes Based Drugs and Genes Co-delivery Systems.
AB  - There are several mechanisms by which cancer cells develop resistance to
      treatments, including increasing anti-apoptosis, increasing drug efflux, inducing
      angiogenesis, enhancing DNA repair and altering cell cycle checkpoints. The drugs
      are hard to reach curative effects due to these resistance mechanisms. It has
      been suggested that liposomes based co-delivery systems, which can deliver drugs
      and genes to the same tumor cells and exhibit synergistic anti-cancer effects,
      could be used to overcome the resistance of cancer cells. As the co-delivery
      systems could simultaneously block two or more pathways, this might promote the
      death of cancer cells by sensitizing cells to death stimuli. This article
      provides a brief review on the liposomes based co-delivery systems to overcome
      cancer resistance by the synergistic effects of drugs and genes. Particularly,
      the synergistic effects of combinatorial anticancer drugs and genes in various
      cancer models employing multifunctional liposomes based co-delivery systems have
      been discussed. This review also gives new insights into the challenges of
      liposomes based co-delivery systems in the field of cancer therapy, by which we
      hope to provide some suggestions on the development of liposomes based co
      delivery systems.

PMID- 29332571
TI  - Role of Heart Rate Reduction in the Management of Myocarditis.
AB  - The morbidity of myocarditis demonstrates an upward tendency by years, is
      commonly defined as the inflammation of myocytes and is caused by multiple
      factors. With the development of the molecular biological technique, great
      breakthroughs in the diagnosis and understanding of pathophysiological mechanisms
      of myocarditis have recently been achieved. Several questions remain unresolved,
      however, including standard treatment approaches to myocarditis, which remain
      controversial and ambiguous. Heart rate, as an independent risk factor, has been
      shown to be related to cardiac disease. Recent studies also show that the
      autonomic nervous system is involved in immunomodulatory myocarditis processes.
      Heart rate reduction treatment is recommended in myocarditis based on a number of
      animal experiments and clinical trials. It is possible that heart rate-lowering
      treatments can help to attenuate the inflammatory response and myocyte injury and
      reverse ventricular remodeling. However, how to execute the protective effects of
      heart rate reduction on myocarditis is still not clear. In this review, we
      discuss the pathogenesis and pathophysiological process of viral myocarditis and
      propose heart rate lowering as a therapeutic target for myocarditis, especially
      in light of the third-generation beta-blockade carvedilol and funny channel
      blocker ivabradine. We also highlight some additional beneficial effects of such
      heart rate reduction agents, including anti-inflammatory, antioxidation, anti
      nitrosative stress, anti-fibrosis and antiapoptosis properties.

PMID- 29332572
TI  - Lipoprotein-associated Phospholipase A2 and Coronary Heart Disease.
AB  - In the last decades, the role of inflammation in the pathogenesis of
      atherosclerosis has been the topic of intense research. Several markers of
      inflammation have shown predictive value for first and recurrent coronary events
      in patients without and with established Coronary Heart Disease (CHD). Among
      these markers, lipoprotein- associated phospholipase A2 (Lp-PLA2) has recently
      received considerable attention. In the present review, the potential role of Lp
      PLA2 as a marker of CHD risk and as a therapeutic target is discussed. Elevated
      Lp- PLA2 mass and activity appears to be associated with increased risk for CHD,
      both in the general population and in patients with established CHD. However, it
      is unclear whether the measurement of Lp-PLA2 improves risk discrimination when
      incorporated in models that include traditional cardiovascular risk factors.
      Moreover, the lack of effect on CHD events of darapladib, a potent, selective Lp
      PLA2 inhibitor, in two large, randomized, placebo-controlled trials and the
      mostly negative findings of genetic association studies suggest that Lp-PLA2 is
      unlikely to represent a causal factor in atherogenesis. Therefore, it is doubtful
      whether Lp-PLA2 will constitute a therapeutic target for the prevention of CHD.

PMID- 29332573
TI  - Torsades de Pointes in Patients with Polymyalgia Rheumatica.
AB  - Polymyalgia rheumatica (PMR) represents the most common inflammatory rheumatic
      disease of the elderly. It is characterized by synovitis of proximal joints and
      extra-articular synovial structures, along with chronic high-grade systemic
      inflammation. PMR is closely related to giant cell arteritis (GCA), a large
      vessel vasculitis that involves the major branches of the aorta, particularly the
      extracranial branches of carotid artery including temporal arteries. It is
      currently believed that PMR and GCA may represent different manifestations of the
      same disease process. Chronic systemic inflammation is presently recognized as
      one of the key pathogenic mechanisms underlying cardiovascular disease and
      associated complications, including cardiac arrhythmias and sudden death. In this
      regard, several studies demonstrated that besides promoting structural heart
      disease, inflammatory activation may also be per se arrhythmogenic, via cytokine
      mediated effects on cardiac electrophysiology. In particular, increasing evidence
      points to inflammation as a novel risk factor for QTc prolongation and related
      life-threatening arrhythmias, specifically Torsade de Pointes (TdP). Starting
      from the report of two cases of TdP occurring in PMR patients with active disease
      and elevated circulating IL-6 levels, we here reviewed literature data regarding
      heart involvement and arrhythmic events in PMR/GCA, as well as TdP risk in
      inflammatory diseases. Potential underlying mechanisms were dissected, by
      focusing on the driving role of inflammatory activation.

PMID- 29332574
TI  - Biomacromolecular Based Fibers in Nanomedicine: A Combination of Drug Delivery
      and Tissue Engineering.
AB  - BACKGROUND: Biopolymers based materials (polysaccharides, lipids, proteins, and
      nucleic acids) are one of the basic resources in bio-engineering sciences because
      of desirable features. Moreover, nanobiotechnology innovates nanomaterial and
      associated technique in nano medicine (drug delivery and tissue engineering).
      METHODS: In the nano-medicine, fibers are introduced as a successful biomimetic
      extracellular matrix scaffolds and drug carrier systems. Electrospinning as a
      simple and cost-effective technique is used to design nanofibers. Natural
      polymers including chitosan, alginic acid, hyaluronic acid, collagen, gelatin,
      and albumin are excellent candidates for electrospinning. However, these types of
      biopolymers typically have difficulty in electrospinning. RESULTS: Therefore, for
      spinning of these polymers, the condition of the procedure including solvent,
      copolymer addition, cross-linker addition, and optimization of spinning should be
      done. CONCLUSION: The present study gathered information about fiber-based
      nanodevices from biopolymers in a drug transportation or tissue engineering.

PMID- 29332576
TI  - Current Understanding of Physicochemical Mechanisms for Cell Membrane Penetration
      of Arginine-rich Cell Penetrating Peptides: Role of Glycosaminoglycan
      Interactions.
AB  - Arginine-rich cell penetrating peptides (CPPs) are very promising drug carriers
      to deliver membrane-impermeable pharmaceuticals, such as siRNA, bioactive
      peptides and proteins. CPPs directly penetrate into cells across cell membranes
      via a spontaneous energy-independent process, in which CPPs appear to interact
      with acidic lipids in the outer leaflet of the cell membrane. However, acidic
      lipids represent only 10 to 20% of the total membrane lipid content and in
      mammalian cell membranes they are predominantly located in the inner leaflet.
      Alternatively, CPPs favorably bind in a charge density- dependent manner to
      negatively charged, sulfated glycosaminoglycans (GAGs), such as heparan sulfate
      and chondroitin sulfate, which are abundant on the cell surface and are involved
      in many biological functions. We have recently demonstrated that the interaction
      of CPPs with sulfated GAGs plays a critical role in their direct cell membrane
      penetration: the favorable enthalpy contribution drives the high-affinity binding
      of arginine-rich CPPs to sulfated GAGs, initiating an efficient cell membrane
      penetration. The favorable enthalpy gain is presumably mainly derived from a
      unique property of the guanidino group of arginine residues forming multidentate
      hydrogen bonding with sulfate and carboxylate groups in GAGs. Such interactions
      can be accompanied with charge neutralization of arginine-rich CPPs, promoting
      their partition into cell membranes. This review summarizes the current
      understanding of the physicochemical mechanism for lipid membrane penetration of
      CPPs, and discusses the role of the GAG interactions on the cell membrane
      penetration of CPPs.

PMID- 29332575
TI  - Protective Role of Italian Juglans regia L. nut Ethanolic Extract in Human
      Keratinocytes under Oxidative and Inflammatory Stress.
AB  - OBJECTIVE: In this research, fatty acid profile and polyphenolic content of an
      ethanolic extract of walnut from Juglans regia L. collected in Central Italy,
      were characterized. The potential antioxidant and anti-inflammatory effects of
      the extract were investigated in the human keratinocytes cell line. METHODS:
      Fatty acid profile was determined by gas chromatography/mass spectrometry
      analysis, total phenolic content by Folin-Ciocalteu method and aluminum chloride
      colorimetric method was used for determination of total flavonoids.
      Kertatinocytes were exposed to t-butyl hydroperoxide or Tumor Necrosis Factor
      alfa in the absence or presence of extract. Reduced glutathione was determined by
      Sedlak method; lipid peroxidation was assessed by measuring thiobarbituric acid
      reactive substances. t-butyl hydroperoxide and Tumor Necrosis Factor alfa-induced
      intracellular reactive oxygen species were monitored by fluorescent probes. The
      expression of some genes related to the inflammatory process (IL-6, IL-8, ikB,
      and ICAM) were analysed by Real-time PCR. RESULTS: JRE contains a favourable
      fatty acid profile with low saturated fats (19%) and high-unsaturated fats (81%)
      with a prevalence of the omega-6 linoleic acid (48%). Also a significant amount
      of polyphenols was found (5,0052 mg gallic acid equivalent/gdw). Antioxidant and
      anti-inflammatory properties of JRE were observed on analysed cellular model. JRE
      antioxidants counteracted ROS production, GSH depletion and lipid peroxidation as
      well downregulated the expression of some genes related to the inflammatory
      process. Moreover, polyunsaturated fatty acids exhibited anti-inflammatory
      properties. CONCLUSION: The obtained results uphold walnut as dietary adjunct in
      health promotion and drive towards its development in drug therapy against
      chronic inflammatory disorders, including inflammatory skin diseases.

PMID- 29332577
TI  - The Potential Use of Peptides in Cancer Treatment.
AB  - Conventional chemotherapeutic drugs have significant limitations. For example,
      tumors may develop resistance, cancers may relapse after treatment, and the drugs
      may induce secondary malignancies in the treatment of metastatic cancer. There is
      still a great need for drugs that are able to destroy cancer cells selectively,
      that is, to effectively treat slow-growing and dormant cells without being
      affected by chemoresistance mechanisms. A growing number of studies indicate that
      peptides may be beneficial for drug discovery and development. Peptides offer
      minimal immunogenicity, excellent tissue penetrability, low-cost
      manufacturability, and ease of modification for enhancing in vivo stability and
      biological activity, properties which make them ideal candidates for cancer
      treatment. This review highlights recent advances in and future prospects for the
      application of peptides as therapeutic agents for cancer therapy. We discuss the
      application of peptides in cancer therapy, alone and in combination with other
      peptides or small-molecule chemotherapeutic drugs, for use in targeted cancer
      therapy. Furthermore, we consider the use of peptides as a carrier for targeted
      molecular imaging in the diagnosis and follow-up treatment of cancer. This
      account also reviews the challenges of using peptide drugs and ways to overcome
      these limitations. The results obtained in studies presented in this paper
      indicate that peptides are promising candidates for targeted cancer therapy.

PMID- 29332578
TI  - Amyloid-beta Inhibits PDGFbeta Receptor Activation and Prevents PDGF-BBInduced
      Neuroprotection.
AB  - BACKGROUND: PDGFbeta receptors and their ligand, PDGF-BB, are upregulated in vivo
      after neuronal insults such as ischemia. When applied exogenously, PDGF-BB is
      neuroprotective against excitotoxicity and HIV proteins. OBJECTIVE: Given this
      growth factor's neuroprotective ability, we sought to determine if PDGF-BB would
      be neuroprotective against amyloid-beta (1-42), one of the pathological agents
      associated with Alzheimer's disease (AD). METHODS AND RESULTS: In both primary
      hippocampal neurons and the human-derived neuroblastoma cell line, SH-SY5Y,
      amyloid-beta treatment for 24 h decreased surviving cell number in a
      concentrationdependent manner. Pretreatment with PDGF-BB failed to provide any
      neuroprotection against amyloid-beta in primary neurons and only very limited
      protective effects in SH-SY5Y cells. In addition to its neuroprotective action,
      PDGF promotes cell growth and division in several systems, and the application of
      PDGFBB alone to serum-starved SH-SY5Y cells resulted in an increase in cell
      number. Amyloid-beta attenuated the mitogenic effects of PDGF-BB, inhibited PDGF
      BB-induced PDGFbeta receptor phosphorylation, and attenuated the ability of PDGF
      BB to protect neurons against NMDA-induced excitotoxicity. Despite the ability of
      amyloid-beta to inhibit PDGFbeta receptor activation, immunoprecipitation
      experiments failed to detect a physical interaction between amyloid-beta and PDGF
      BB or the PDGFbeta receptor. However, G protein-coupled receptor transactivation
      of the PDGFbeta receptor (an exclusively intracellular signaling pathway)
      remained unaffected by the presence of amyloid-beta. CONCLUSIONS: As the PDGF
      system is upregulated upon neuronal damage, the ability of amyloid-beta to
      inhibit this endogenous neuroprotective system should be further investigated in
      the context of AD pathophysiology.

PMID- 29332579
TI  - Alzheimer's Disease: A Systemic Review of Substantial Therapeutic Targets and the
      Leading Multi-functional Molecules.
AB  - Alzheimer's Disease (AD) is a fatal neurodegenerative disorder, having a complex
      aetiology with numerous possible drug targets. There are targets that have been
      known for years while more new targets and theories have also emerged. Beta
      amyloid and cholinesterases are the most significant biological targets for
      finding curative treatment of AD. The major class of drugs used for AD till now
      has been the Cholinesterase (ChE) inhibitors. Other prevailing models of
      molecular pathogenesis in AD include Neurofibrillary Tangles (NFTs) and amyloid
      deposition, tryptophan degradation pathway, kinase and phosphatase activity
      imbalance and neuroinflammation. The beta amyloid aggregation initiates flow of
      events resulting in neurotoxicity and finally clinical pathogenesis of AD.
      Furthermore, ApoE is another very significant entity involved in repairing and
      maintaining the neurons and has important role in neurodegeneration.
      Neuroinflammation being the primmest symptom for AD is essential to focus on.
      Multiple factors and complexity in interlinking disease progression pose huge
      challenge to find one complete curing drug. With so many promising molecules
      having multiform pharmacological profile from all over the world however facing
      failures in clinical trials indicates the need to consider all aspects of the old
      as well as new therapeutic targets of AD. Until the disease mechanism is better
      understood, it is likely that multiple targeting, symptomatic and
      diseasemodifying, is the way forward. Most recent approaches to find anti
      Alzheimer's agents have focused on multi-target directed agents that include
      targeting all glorious targets hypothesized against AD. New identification of
      prototype candidates that could be starting point of a new way of thinking drug
      design has been done and many drug candidates are under preclinical evaluation.
      The main focus of this review is to discuss the recent understanding of key
      targets and the development of potential therapeutic agents for the treatment of
      AD. It also documents the current therapeutic agents in clinical trials and under
      development based on their main mode of action.

PMID- 29332580
TI  - Aurora Kinase Inhibitors in Head and Neck Cancer.
AB  - Aurora kinases are a group of serine/threonine kinases responsible for the
      regulation of mitosis. In recent years, with the increase in Aurora kinase
      related research, the important role of Aurora kinases in tumorigenesis has been
      gradually recognized. Aurora kinases have been regarded as a new target for
      cancer therapy, resulting in the development of Aurora kinase inhibitors. The
      study and application of these small-molecule inhibitors, especially in
      combination with chemotherapy drugs, represent a new direction in cancer
      treatment. This paper reviews studies on Aurora kinases from recent years,
      including studies of their biological function, their relationship with tumor
      progression, and their inhibitors.

PMID- 29332581
TI  - Cetuximab and the Head and Neck Squamous Cell Cancer.
AB  - The Head and Neck Squamous Cell Cancer (HNSCC) is the most common type of head
      and neck cancer (more than 90%), and all over the world more than a half million
      people have been developing this cancer in the last years. This type of cancer is
      usually marked by a poor prognosis with a really significant morbidity and
      mortality. Cetuximab received early favor as an exciting and promising new
      therapy with relatively mild side effect, and due to this, received authorization
      in 2004 from the European Medicines Agency (EMA) and in 2006 from the Food and
      Drug Association (FDA) for the treatment of patients with squamous cell cancer of
      the head and neck in combination with radiation therapy for locally advanced
      disease. In this work we will review the application and the efficacy of the
      Cetuximab in the treatment of the HNSCC.

PMID- 29332582
TI  - Dual BACE-1/GSK-3beta Inhibitors to Combat Alzheimer's Disease: A Focused Review.
AB  - In industrialized countries, Alzheimer's disease represents the most devastating
      neurodegenerative disorder in elderly people and the search for a disease
      modifying agent is still justified by this unmet need. Several possible targets
      have been explored to find an appropriate drug therapy, and in this review, dual
      inhibitors of beta secretase and glycogen synthase kinase 3, recently reported in
      literature, will be appraised. Applying a ligand-based approach, the triazinone
      core emerged as a suitable scaffold to simultaneously bind the aspartic dyad of
      BACE-1 and the ATP site of GSK-3beta, leading to a series of small molecules
      endowed with a balanced micromolar affinity and a promising pharmacokinetic
      profile. Differently, by means of a structure-based approach, a series of well
      balanced dual binding molecules were designed, taking advantage of the
      versatility of the curcumin scaffold. For some of these new compounds a potential
      neuroprotective effect was also observed, due to their ability to counteract the
      oxidative stress through the inhibition of NQO1 enzyme. Finally, different
      virtual screening analyses were performed, leading to the identification of new
      potential scaffolds deserving further development.

PMID- 29332583
TI  - Eating Green: Shining Light on the Use of Dietary Phytochemicals as a Modern
      Approach in the Prevention and Treatment of Head and Neck Cancers.
AB  - Enthusiasm for the use of dietary bioactive compounds as chemopreventive agents
      and adjuvants for current therapies has increased laboratory research conducted
      on several types of cancers including Head and Neck Squamous Cell Carcinoma
      (HNSCC). The green chemoprevention movement is a modern approach to highlight
      healthy lifestyle changes that aim to decrease the incidence of HNSCC. A healthy
      diet can be an effective way to prevent the development of oral cancers.
      Discovery of the naturally occurring plant based compounds called phytochemicals
      has facilitated the development of new treatment strategies for patients that are
      at risk for, or have developed HNSCC. Many of these compounds have been shown to
      elicit very potent anti-carcinogenic properties. While there are many compounds
      that have been studied, the compounds from two specific categories of
      phytochemicals, phenolics (resveratrol, EGCG, curcumin, quercetin, and honokiol)
      and glucosinolates (sulforaphane, PEITC and BITC), are emerging as potent and
      effective inhibitors of oral carcinogenesis. These compounds have been shown to
      inhibit HNSCC growth through a variety of mechanisms. Research has demonstrated
      that these compounds can regulate cancer cell proliferation through the
      regulation of multiple cell signaling pathways. They can impede cell cycle
      progression, induce differentiation and apoptosis, prevent angiogenesis, and
      inhibit cancer cell invasive and metastatic properties. They can protect normal
      cells during treatment and reduce the damage caused by chemotherapy and
      radiotherapy. This review aims to provide an overview of some of the most
      effective phytochemicals that have the potential to successfully prevent and
      treat head and neck squamous cell carcinoma.

PMID- 29332584
TI  - Multicomponent Reactions for Multitargeted Compounds for Alzheimer's Disease.
AB  - Alzheimer's Disease (AD) is a multifactorial and fatal neurodegenerative disorder
      affecting around 35 million people worldwide, which is characterized by decline
      of cholinergic function, deregulation of amyloid beta (Abeta) oligomers formation
      and Abeta fibril deposition. Multi-Target- Directed Ligands (MTDLs) have emerged
      as an original strategy for developing new therapeutic agents on AD.
      Multicomponent Reactions (MCRs) are a useful alternative to sequential multistep
      syntheses, allowing scaffold diversity and a rapid and easy access to
      biologically relevant compounds. The biological diversity of MCRs is very rich
      providing great possibilities for researchers interested in bioactive small
      molecular weight compounds. Since the MTDL strategy has been used to develop
      compounds endowed with the capacity to interact with different targets, versatile
      compound libraries may be obtained by MCRs according to the well established
      features of each target. Thus, either MTDLs or monotarget compounds have been
      developed by MCRs to address different factors implicated in AD. This work
      focuses on antioxidants, calcium channel modulators, both AChE and BuChE
      inhibitors, BACE1 inhibitors, and modulators of the nuclear factor (erythroid
      derived 2)-like 2. First, we discuss the Biginelli reaction and its use for
      developing new interesting compounds for AD, followed by the contribution of Ugi
      reaction and, finally, the interest of other MCRs in the same topic.

PMID- 29332585
TI  - New Tacrines as Anti-Alzheimer's Disease Agents. The (Benzo)Chromeno-
      PyranoTacrines.
AB  - Tacrine was the first drug approved by FDA (US) for the treatment of Alzheimer's
      disease suffering patients. Nowadays, this agent has been withdrawn from the
      clinics due to secondary effects, which, most importantly, include
      hepatotoxicity. However, the research on new tacrine analogues devoid of these
      therapeutically undesirable effects, but benefiting of their high and well known
      positive cholinergic power, has produced a number of new non-hepatotoxic
      tacrines. In this context, our laboratory has recently prepared a new set of
      heterocyclic tacrines by changing the benzene ring present in tacrine by
      appropriate heterocyclic motifs. Based on this approach, in this review we
      summarize the results that we have found in the ChromenoPyranoTacrines, one of
      the families of tacrine analogues. This highlights their pharmacological profile,
      such as their cholinesterase inhibition power, calcium channel blockade,
      antioxidant capacity, Abeta-anti-aggregating, and neuroprotective properties. As
      a result of this work we have identified permeable, neuroprotective MTD tacrines
      racemic hit-tacrines 11-amino-12-(3,4,5-trimethoxyphenyl)-7,9,10,12-tetrahydro-8H
      chromeno[2,3- b]quinolin-3-ol (6g) and 14-(3,4-dimethoxyphenyl)-9,11,12,14
      tetrahydro-10H-benzo[5,6] chromeno [2,3-b] quinolin-13-amine (7i),devoid of toxic
      effects and showing potent anti-cholinesterasic properties, that deserve
      attention and further development in order to find new, and more efficient drugs,
      for AD therapy.

PMID- 29332586
TI  - Recent Developments on Multi-Target-Directed Tacrines for Alzheimer's Disease. I.
      The Pyranotacrines.
AB  - Tacrine was the first drug to display beneficial effects on cognitive impairment
      of Alzheimer Disease (AD) patients. Unfortunately, many treated patients
      displayed related hepatotoxicity, and hence this drug was withdrawn.
      Notwithstanding, recent efforts have been directed to design small tacrine
      analogues targeting the underlying pathogenic mechanisms of AD. In this context,
      we have developed a number of pyranotacrines by changing the benzene fused ring
      in tacrine by a 4Hpyran. Based on this strategy, in this account we will show the
      tacrine analogues that we have designed, synthesized and evaluated as potential
      multipotent agents for AD in the last years. We have demonstrated that this
      approach is possible, and that a number of readily available tacrine analogues
      show cholinesterase inhibition power, as well as other pharmacological
      properties, such as calcium channel blockade, antioxidant properties,
      neuroprotection, Abeta-amyloid inhibition aggregation capacity, etc., making them
      suitable multipotent molecules for further development for the potential
      treatment of AD.

PMID- 29332587
TI  - Lysosomal Acid Lipase Deficiency: Could Dyslipidemia Drive the Diagnosis?
AB  - LAL-deficiency (LAL-D) is a rare and systemic condition, secondary to LIPA gene
      mutations, responsible for lysosomal accumulation of cholesteryl esters and
      triglycerides, whose manifestations are very heterogeneous in terms of the age of
      onset, severity and the type of clinical and radiological manifestations.
      Dyslipidemia, hepatomegaly and hepatosteatosis with increased levels of
      transaminases are the most common features. The increased risk of premature
      atherosclerosis and cardiovascular disorders, secondary to a generalized
      alteration of lipid profile and lipoprotein dysfunction associated with LAL-D,
      has been increasingly pointed out. Therefore, medical awareness towards LAL
      deficiency should be increased, since this condition has to be considered in the
      differential diagnosis of pediatric conditions manifested with dyslipidemia and
      hepatic accumulation of intracellular products. On the other hand, early patient
      identification and management remain challenging.

PMID- 29332588
TI  - Treatment Strategies for Hypercholesterolemia.
AB  - BACKGROUND: Atherosclerotic disease is a leading cause of morbidity and mortality
      in adults and is generally thought of as only affecting adults. However, the
      pathologic changes in vessels leading to atherosclerosis, and an increased risk
      of cardiovascular disease, have been shown to begin in early adolescence.
      OBJECTIVES: There is a growing body of literature suggesting that earlier
      treatment, through lifestyle changes and pharmacotherapy, can help reduce this
      risk. A growing number of children are presenting with elevated cholesterol
      because of the increased prevalence of obesity and diabetes mellitus. METHODS: In
      addition, an increasing number of children are living with previously fatal
      diseases that increase the risk of atherosclerosis, either because of the disease
      process or as adverse effect of the treatment, such as human immunodeficiency
      virus, Kawasaki disease, and cardiac transplantation. RESULT AND CONCLUSION: In
      addition, specific disorders of cholesterol metabolism, such as Familial
      Hypercholesterolemia (FH) may be encountered in a pediatric practice.

PMID- 29332589
TI  - Validation of an Arabic Version of the Obesity-Related Wellbeing (ORWELL 97)
      Questionnaire in Adults with Obesity.
AB  - BACKGROUND: No specific questionnaire that evaluates Health-Related Quality Of
      Life (HRQOL) in individuals with obesity is available in the Arabic language. The
      aim of this study was therefore to propose and examine the validity and
      reliability of an Arabic language version of the ORWELL 97, a validated obesity
      related HRQOL questionnaire. METHODS: The ORWELL 97 questionnaire was translated
      from English to Arabic language and administered to 318 Arabic-speaking
      participants (106 from clinical and 212 from community samples), and underwent
      internal consistency, test-retest reliability, construct and discriminative
      validity analysis. RESULTS: Internal consistency and the test-retest reliability
      were excellent for ORWELL 97 global scores in the clinical sample. Participants
      with obesity displayed significantly higher ORWELL 97 scores than participants
      from the community sample, confirming the good discriminant validity of the
      questionnaire. Confirmatory factor analysis in the clinical sample revealed a
      good fit for a modified two-factor structure. CONCLUSION: Overall, the Arabic
      version of the ORWELL 97 can be considered validated in Arabic adult patients
      with obesity, paving the way to further assessment of its responsiveness in
      measuring changes in health-related quality of life associated with obesity
      treatment.

PMID- 29332590
TI  - Oxidative Stress and Cardiac Remodeling: An Updated Edge.
AB  - BACKGROUND: A common phenotype associated with heart failure is the development
      of cardiac hypertrophy. Cardiac hypertrophy occurs in response to stress, such as
      hypertension, coronary vascular disease, or myocardial infarction. The most
      critical pathophysiological conditions involved may include dilated hypertrophy,
      fibrosis and contractile malfunction. The intricate pathophysiological mechanisms
      of cardiac hypertrophy have been the core of several scientific studies, which
      may help in opening a new avenue in preventive and curative procedures.
      OBJECTIVES: To our knowledge from the literature, the development of cardiac
      remodeling and hypertrophy is multifactorial. Thus, in this review, we will focus
      and summarize the potential role of oxidative stress in cardiac hypertrophy
      development. CONCLUSION: Oxidative stress is considered a major stimulant for the
      signal transduction in cardiac cells pathological conditions, including
      inflammatory cytokines, and MAP kinase. The understanding of the
      pathophysiological mechanisms which are involved in cardiac hypertrophy and
      remodeling process is crucial for the development of new therapeutic plans,
      especially that the mortality rates related to cardiac remodeling/dysfunction
      remain high.

PMID- 29332591
TI  - Anti-Trypanosoma cruzi Activity in vitro of Phases and Isolated Compounds from
      Excoecaria lucida Leaves.
AB  - BACKGROUND: Chagas disease is caused by the protozoan parasite Trypanosoma cruzi.
      This illness is found mainly in 21 Latin American countries and an estimated 8
      million people are infected worldwide. The unsatisfactory chemotherapy provokes
      severe toxicity and resistant strains. Medicinal plants constitute a promising
      source of new drugs and remedies against all kinds of disorders, mainly
      infectious diseases arousing interest worldwide. OBJECTIVE: The aim of this study
      is the isolation, structural identification and evaluation of the trypanocidal
      activity of samples present in the Excoecaria lucida Sw. leaves. METHODS: Total
      extract (TE) of E. lucida Sw. leaves was obtained by ethanol extract therefore
      fractionated sequentially with hexane, ethyl acetate and n-butanol, to obtain
      three phases: Hex, EA and But, respectively. Ellagic acid (EL1) was purified from
      both EA and But phases, while EL2; a 1:1 stigmasterol-3-O-beta-D-glucopyranoside
      plus sitosterol-3-O-beta-D-glucopyranoside mixture was obtained from the Hex
      phase. Activity assays were performed using bloodstream and intracellular forms
      of T. cruzi and cytotoxicity assays using L929 fibroblasts. RESULTS: The EL1 and
      EL2 samples were more active against bloodstream trypomastigote forms with EC50
      of 53.0+/-3.6 and 58.2+/-29.0 ug/mL, respectively; at 100 ug/mL. These samples
      also showed 70% of inhibition of L929 cells infection. Toxicity assays
      demonstrated that after 96 h of treatment only the fractions Hex and EA presented
      detectable cytotoxicity. CONCLUSION: Ellagic acid, stigmasterol-3-O-beta-D
      glucopyranoside and sitosterol-3-O-beta-Dglucopyranoside are reported for the
      first time in E. lucida Sw. leaves as well as their biological activity studies
      supporting further investigations for Chagas disease treatment.

PMID- 29332592
TI  - Construction of an M1GS Ribozyme for Targeted and Rapid mRNA Cleavage;
      Application on the Ets-2 Oncogene.
AB  - BACKGROUND: RNase P-mediated cleavage of target RNAs has been proposed as a
      promising tool for gene silencing. Ets-2 proto-oncogene controls the expression
      of a wide variety of genes involved in cancer and immunity. OBJECTIVE:
      Construction of a functional RNase P-based ribozyme (M1GS303) that targets Ets-2
      mRNA. METHODS: The accessible sites for targeting of Ets-2 mRNA were identified
      by footprinting analysis. M1GS303 ribozyme was constructed by cloning. The
      activity of the ribozyme in the presence or absence of spiramysin in E. coli
      cells and human cell lines was quantified by RT-PCR. The efficiency of the
      ribozyme in silencing the endogenous expression of Ets-2 in human cell lines was
      examined by RT-PCR, western blot and immunofluorescence analysis. RESULTS: In E.
      coli cells co-transformed with plasmids bearing M1GS303 and the ets-2 target
      gene, Ets-2 mRNA was decreased by 93% 12h after IPTG induction in the absence,
      and after 4h in the presence of spiramycin. Ets-2 was rapidly downregulated in
      the human embryonic kidney cell line HEK293 and the T-cell line Jurkat
      transfected with an M1GS303 plasmid; the silencing effect of M1GS303 was
      considerably faster when the cells were cultured with spiramycin. In Jurkat
      cells, Ets-2-downregulation resulted in upregulation of the expression of IL-2,
      IL-4 and IFN-alpha cytokine genes that have Ets-2 binding sites on their
      promoters, whereas it had no effect on the expression of the IL-10 gene that
      lacks Ets-2 binding sites on its promoter. CONCLUSIONS: M1GS303 ribozyme cleaves
      effectively Ets-2 mRNA in bacteria and mammalian cells, and its activity is
      enhanced by spiramycin. Downregulation of ets-2 gene in the T-cell line Jurkat
      upregulates IL-2, IL-4 and IFN-alpha cytokine genes. M1GS technology may be a
      better alternative to conventional gene-interference therapies and the
      delineation of the effects of gene silencing in various pathologies.

PMID- 29332593
TI  - Facile Synthesis, Crystal Structure, DFT Calculation and Biological Activities of
      4-(2-fluorophenyl)-3-(3-methoxybenzyl)-1H-1,2,4-triazol-5 (4H)-one (5).
AB  - BACKGROUND: In the past few decades, design, synthesis, and characterization of
      novel heterocyclic compounds with auspicious biological profile received the
      considerable attention of the scientific community. Among them, the small and
      simple organic molecular backbone like triazole moiety have a broad spectrum of
      applications in the medicinal as well as diagnostic areas. OBJECTIVE: The
      objective of present study was synthesis, characterization, and exploration of
      biological profile of 4-(2-fluorophenyl)-3-(3-methoxybenzyl)-1H-1,2,4-triazole
      5(4H)-one (5). The tautomeric interconversion of the molecule was observed by the
      single crystal XRD and DFT analysis. METHODS: N-(2-fluorophenyl)-2-[2-(3
      methoxyphenyl)acetyl]hydrazine carboxamide (4) was synthesized by the
      condensation of 2-(3-methoxyphenyl)acetohydrazide (3) with 1-fluoro-2-
      isocyanatobenzene. The dehydrocyclization of compound (4) yielded target compound
      (5) by refluxing in 2 N aqueous sodium hydroxide solutions. The target molecule
      was characterized by FTIR, 1H NMR, 13C NMR, single crystal X-ray diffraction
      analysis and DFT calculation. The enzymatic assay measurements were carried out
      by using a microplate reader (OPTI Max, Tunable Microplate Reader; Wavelength
      range: 340-850 nm; for 96-well plates) while DFT calculation was performed by
      Gaussian 09 package. RESULTS: The XRD result and DFT calculations showed that
      molecule 5 predominantly exists in thione conformation and crystallized in the
      triclinic system of P-1 space group. Furthermore, for the practical applicability
      of synthesized compound 5, the in vitro acetylcholinesterase as well as alpha
      glucosidase inhibition activities were performed and found moderate enzyme
      inhibition potential comparable with that of reference inhibitors. CONCLUSION:
      This study might be helpful for future design and development of potent enzyme
      inhibitor to control Alzheimer's as well as diabetic disease. The DFT and single
      crystal XRD analysis data might be helpful for understanding the mechanism of
      drug binding and its mode of action.

PMID- 29332595
TI  - New Bis-Pyrazolones as Potential Leads for ROS Inhibition; Environment Friendly
      Green Synthesis, Structural Characterization, and In Vitro Studies.
AB  - BACKGROUND: Pyrazolones have identified as significant antioxidant agents and
      many marketed and clinically prescribed NSAIDs have pyrazolone ring as main
      scaffold. METHOD: Keeping in consideration the antioxidant potential of
      pyrazolone scaffold, new bispyrazolones 3-30 were synthesized by a green and
      enviroment friendly reaction route, in which two equivalents of 1-(4
      chlorophenyl)-3-methyl-1H-pyrazol-5-ol were treated with one equivalent of
      benzaldehyde derivatives without any catalyst. All compounds were structurally
      characterzied by 1H-NMR and FAB analysis. 13C-NMR of selected compounds was also
      recorded. All compounds gave satisfactory elemental analyses and found in good
      agreement with calculated values. RESULTS: Synthetic bis-pyrazolones 3-30 were
      evaluated for their oxidative burst inhibitory effect of zymosan stimulated whole
      blood phagocytes by using luminol enhanced chemilluminescence technique. All
      molecules demonstrated the potent ROS inhibition activity in the range of IC50 =
      1.2 +/- 0.1-48.8 +/- 3.9 uM as compared to the standard ibuprofen (IC50 = 54.2 +/
      9.2 MUM). The purity of active compounds was checked by HPLC. CONCLUSION: This
      study has identified a number of non-acidic lead molecules for future research on
      ROS inhibitors.

PMID- 29332594
TI  - In vitro and in silico Evaluation of Non-Quaternary Reactivators of AChE as
      Antidotes of Organophosphorus Poisoning - a New Hope or a Blind Alley?
AB  - BACKGROUND: In the last decade, the concept of uncharged reactivators potentially
      able to penetrate the CNS has been introduced as an alternative to the classic
      charged oxime reactivators. However, this concept brings with it several
      associated drawbacks such as higher lipophilicity, difficulty in administration,
      lower affinity to cholinesterases, and higher toxicity risk. OBJECTIVE: In this
      study, we compare data obtained for a set of five classic charged reactivators
      and a set of three recently published uncharged oximes supplemented by two novel
      ones. METHODS: This time, we used only in silico prediction and in vitro
      approaches. RESULTS: Our data showed that tested uncharged oximes have low
      affinity for cholinesterases, do not possess high reactivation potency, and
      certainly represent a greater toxicity risk due to higher lipophilicity. We
      assume that balanced physicochemical properties will be required for the
      successful treatment of OP poisoning. Nevertheless, the compound meeting such
      criteria and pinpointed in silico (K1280) failed in this particular case.
      CONCLUSION: From the presented data, it seems that the concept of uncharged
      reactivators will have to be modified, at least to improve the bioavailability
      and to satisfy requirements for in vivo administration.

PMID- 29332596
TI  - Synthesis of Thiocarbohydrazones and Evaluation of their in vitro Antileishmanial
      Activity.
AB  - BACKGROUND: Leishmaniasis is a protozoan parasitic vector-borne disease which is
      endemic in 88 tropical countries. Infected sandfly is the main vector of this
      disease, while there are several other vectors, parasites, and reservoirs
      involved in the transmission of this disease. Leishmania donovani, L. infantum,
      and L. chagasi are common disease causing species, transmitted through sandflies.
      Leishmaniasis is a neglected tropical disease with broad spectrum of clinical
      manifestations. Cutaneous leishmaniasis is prevalent in many countries, including
      Pakistan. METHODS: Thiocarbohydrazones (1-20) were synthesized through one pot
      method by refluxing thiocarbahydrazide with different substituted benzaldehydes
      in ethanol in the presence of acetic acid as a catalyst. These synthetic
      compounds were evaluated for their potential antileishmanial activity in vitro
      against Leishmania major promastigotes. RESULTS: Compounds 5-8, 11, 14, 16, 17,
      19 and 20 were reported earlier, while compounds 2-4, 9, 10, 12, 13 and 15 were
      identified as were derivatives. Compounds 1-20 demonstrated antileishmanial
      activities with IC50 values between 1.63 +/- 0.05 - 64.82 +/- 0.17 uM, as
      compared to the standard drug pentamidine (IC50 = 5.09 +/- 0.04 uM). Compounds 2
      (IC50 = 1.63 +/- 0.05 uM), 11 (IC50 = 2.33 +/- 0.01 uM), 4 (IC50 = 11.03 +/- 0.20
      uM), and 10 (IC50 = 11.63 +/- 0.06 uM) displayed comparable antileishmanial
      activities to the standard drug pentamidine. However, compounds 13, 15-17, and 20
      with IC50 values 36.95 +/- 0.025, 64.82 +/- 0.17, 64.27 +/- 0.38, 62.34 +/- 0.38,
      and 40.47 +/- 0.05 uM, respectively, showed a moderate antileishmanial activity.
      In contrast, compounds 1, 3, 5-9, 12, 14, 18, and 19 demonstrated less than 50%
      growth inhibition of promestigotes of L. major, and thus considered as inactive.
      CONCLUSION: In thiocarbohydrazone derivatives, different substituents at aryl
      part may be responsible for a varying degree of antileishmanial activity in
      vitro. Consequently, these compounds might have a potential for further studies
      as a new class of antileishmanial agents.

PMID- 29332597
TI  - Synthesis of a Novel Class of 1,3-oxathiolane Nucleoside Derivatives of T- 705
      and Evaluation of Their Anti-influenza A Virus and Anti-HIV Activity.
AB  - BACKGROUND: T-705 (Favipiravir) is a broad spectrum antiviral agent approved for
      stockpiling in Japan and currently in Phase 3 testing in the United States.
      Against influenza, it acts as a prodrug, converted intracellularly to selectively
      inhibit viral RNA-dependent RNA polymerase or similar enzymes. This is regarded
      as a novel antiviral mechanism of action, reducing crossresistance to other
      existing anti-influenza drugs. OBJECTIVE: To develop new analogs, a class of 1,3
      oxathiolane nucleoside derivatives of T-705 was designed and synthesized in this
      work. RESULTS: Anti-influenza activity and Anti-HIV activity of these compounds
      were evaluated. Compound 1a displayed activity against A H1N1 with an IC50 of
      40.4 umol/L. Compound 1b showed weak activity against HIV with a viral
      suppression rate of 70-80% at 30 umol/L. CONCLUSION: A class of 1,3-oxathiolane
      nucleoside derivatives of T-705 was designed and synthesized, and one of them was
      identified as a novel scaffold against viral infection.

PMID- 29332598
TI  - Synthesis of New Isoxazole-, Pyridazine-, Pyrimidopyrazines and Their Anti
      Inflammatory and Analgesic Activity.
AB  - BACKGROUND: Isoxazoles, pyridazines, and pyrimidopyrazines have recently
      attracted attention due to their potent pharmacological activities. They
      exhibited anticancer, neuroprotective, analgesic and anti-inflammatory effects.
      OBJECTIVE: The study aimed to synthesize novel isoxazoles, pyridazines, and
      pyrimidopyrazines through efficient high yield protocol for evaluating their
      analgesics and anti-inflammatory activities. METHOD: A series of novel isoxazole
      , pyridazine-, pyrimidopyrazine derivatives was prepared from 5,8-alkyl-1,3
      dimethyl-5,6-dihydropyrimido[5,6-e]pyrazine-2,4,7-trione (1a,b) as the starting
      material. RESULTS: The prepared derivatives were synthesized in moderate to good
      yields (60-75%) in a stepwise efficient protocol under mild condition. These new
      compounds have been proven by several spectroscopic techniques as IR, 1D and 2D
      NMR techniques and mass analysis. The in vivo anti-inflammatory was assessed for
      the synthesized compounds using carrageenan-induced rat hind paw edema model.
      Also, the in vivo analgesic activity for these products was examined utilizing
      hot-plate and acetic acid-induced writhing response assays. CONCLUSION: The
      isoxazole derivatives (3a-f) showed the most forceful anti-inflammatory and
      analgesic activities. Pyrimidopyrazines (4a-f) demonstrated weaker but comparable
      antiinflammatory and analgesic activities to the positive controls.

PMID- 29332599
TI  - The Synthesis of Chalcones as Anticancer Prodrugs and their Bioactivation in CYP1
      Expressing Breast Cancer Cells.
AB  - BACKGROUND: Although the expression levels of many P450s differ between tumour
      and corresponding normal tissue, CYP1B1 is one of the few CYP subfamilies which
      is significantly and consistently overexpressed in tumours. CYP1B1 has been shown
      to be active within tumours and is capable of metabolising a structurally diverse
      range of anticancer drugs. Because of this, and its role in the activation of
      procarcinogens, CYP1B1 is seen as an important target for anticancer drug
      development. OBJECTIVE: To synthesise a series of chalcone derivatives based on
      the chemopreventative agent DMU-135 and investigate their antiproliferative
      activities in human breast cancer cell lines which express CYP1B1 and CYP1A1.
      METHOD: A series of chalcones were synthesised in yields of 43-94% using the
      Claisen-Schmidt condensation reaction. These were screened using a MTT assay
      against a panel of breast cancer cell lines which have been characterised for
      CYP1 expression. RESULT: A number of derivatives showed promising
      antiproliferative activities in human breast cancer cell lines which express
      CYP1B1 and CYP1A1, while showing significantly lower toxicity towards a non
      tumour breast cell line with no CYP expression. Experiments using the CYP1
      inhibitors acacetin and alpha-naphthoflavone provided supporting evidence for the
      involvement of CYP1 enzymes in the bioactivation of these compounds. CONCLUSION:
      Chalcones show promise as anticancer agents with evidence suggesting that CYP1
      activation of these compounds may be involved.

PMID- 29332600
TI  - Finding Novel Anti-carcinomas Compounds by Targeting SFRP4 Through Molecular
      Modeling, Docking and Dynamic Simulation Studies.
AB  - BACKGROUND: Secreted Frizzled-Related Protein 4 (SFRP4) is a glycoprotein that
      acts as a competitor of both canonical and non-canonical Wnt pathways. SFRP4 is
      mostly expressed in ovary and plays a significant role as a target molecule to
      cure ovarian carcinoma. OBJECTIVE: Multiple chemical agonists are being used to
      cure ovary melanoma. We are interested in theoretically analyzing the compounds
      through computational approaches for their potential inhibitory effects against
      SFRP4. METHODS: Compounds were sketched in Chemsketch drawing tool and minimized
      through chimera tool. Because the crystal structure of SFRP4 is not available in
      Protein Data Bank, homology modeling approach was used to predict Three
      Dimensional (3D) crystal structure of SFRP4. Moreover, multiple computational
      approaches such as molecular docking and Molecular Dynamic (MD) simulations along
      with various online tools were employed to screen the best inhibitor against
      ovary melanoma. RESULTS: The docking results showed that 1d and 1e compounds
      revealed significant binding energy values (-9.10 and -9.00 kcal/mol,
      respectively) compared with the standard drugs such as cis-platin and docetaxel (
      3.30, -10.80 kcal/mol), respectively. Moreover, MD simulation results showed that
      1d has little fluctuations throughout the simulation period as depicted by the
      root mean square deviation and root mean square fluctuation graphs. CONCLUSION:
      The present in-silico study provides a deeper insight into the structural
      attributes of 1d compound and its overall molecular interactions against SFRP4
      and gives a hypothetical gateway to use this compound as a potential inhibitor
      against ovarian carcinoma.

PMID- 29332601
TI  - Quantitative Structure-activity Relationship Study of Betulinic Acid Derivatives
      Against HIV using SMILES-based Descriptors.
AB  - BACKGROUND: Human Immunodeficiency Virus (HIV) is the causative agent of Acquired
      Immunodeficiency Syndrome (AIDS) that imposes a global health burden. Therefore,
      HIV therapeutic agents have been discovery and development. OBJECTIVE: To
      construct Quantitative-structure Activity Relationship (QSAR) models of betulinic
      acid derivatives with anti-HIV activity using Simplified Molecular-Input Line
      Entry System (SMILES)- based descriptors. METHODS: A data set of 107 betulinic
      acid derivatives and their anti-HIV activity was used to develop QSAR models. The
      SMILES format of the compounds was employed as descriptors for model construction
      using the CORAL software by means of the Monte Carlo method. RESULTS: Constructed
      QSAR models provided good correlation coefficients (R2) and root mean square
      error (RMSE) with values in the range of 0.5660-0.5890 and 0.963-1.020,
      respectively, for the training set, R2 value of 0.7206-0.7837 and RMSE as 0.609
      1.250, respectively, for the calibration set, and R2 value of 0.6257-0.7748 and
      RMSE as 0.837-0.995, respectively, for the validation set. The best QSAR model
      displayed statistical parameters for training set: R2 = 0.5660 and RMSE = 0.963;
      calibration set: R2 = 0.7273 and RMSE = 0.609, and validation set: R2 = 0.7748
      and RMSE = 0.972. In addition, features of the molecular structure that are
      promoters of the endpoint increase and decrease were defined and discussed. These
      are the basis for the mechanistic interpretation of the suggested models.
      CONCLUSION: These findings provide useful knowledge for guiding the design of
      novel compounds with promising anti-HIV activity.

PMID- 29332602
TI  - Nanoemulsion Strategy for Ursolic and Oleanic Acids Isolates from Plumeria Obtusa
      Improves Antioxidant and Cytotoxic Activity in Melanoma Cells.
AB  - BACKGROUND: Triterpenoids are an important class of natural bioactive products
      present in many medicinal plants. OBJECTIVE: The aim of present study is to
      investigate the antioxidant and anticarcinogenic potential of Oleanolic Acid (OA)
      and Ursolic Acid (UA) on B16 murine melanoma cell line isolated from Plumeria
      obtusa, free and loaded in a nanoemulsion (NEm) system. METHODS: The nanoemulsion
      was characterized by dynamic light scattering, transmission electron microscopy.
      The viscosity was also evaluated. The antioxidant activity was determined by the
      reduction of 2,2-diphenyl-2- picrylhydrazyl (DPPH) free radical. In vitro
      proliferation studies were determined using the sulforhodamine-B method. RESULTS:
      OA/UA natural mixture exhibited high percentage of inhibition of DPPH (86.06% and
      85.12%, with and without irradiation). Percentages of inhibition higher than 85%
      in samples with and without ultraviolet irradiation were recorded when loaded in
      the NEm system. The natural mixture incorporated into the NEm showed cytotoxic
      activity from 2.9 uM, whereas the free compounds from 17.4 uM. CONCLUSION: We
      conclude that these pentacyclic triterpenes loaded in a NEm system could be
      considered as a new potential tool for further investigation as anticancer
      agents.

PMID- 29332603
TI  - Previous use of Statins and Atrial Electrical Remodeling in Patients with
      Cryptogenic Stroke.
AB  - BACKGROUND: In the general population the leading cause of cardioembolic stroke
      is atrial fibrillation (AF). A silent AF is also the possible cause of many
      cryptogenic strokes. P wave dispersion (PWD), a predictor of AF, has been
      proposed as a marker of silent AF occurrence in these strokes. PWD correlates
      with high-sensitive C-reactive protein levels reflecting the role of inflammation
      in promoting a slowed and inhomogeneous atrial conduction. Statins have a
      multitude of additional effects beyond lipid lowering, in particular anti
      inflammatory effects that may influence atrial conduction. OBJECTIVE: The aim of
      this study was to evaluate the effects of previous statin use on PWD in patients
      with cryptogenic stroke, in order to highlight a possible role for statins in
      preventing atrial conduction alterations that predispose to AF. METHOD: We
      enrolled 131 patients (67 males, 64 females; mean age 69+/-13 years) with
      cryptogenic stroke. All patients underwent neuroimaging examination, arterial
      ultrasound examination, echocardiography and ECG. PWD was measured in all
      subjects. RESULTS: Patients previously treated with statins (n: 34) had lower PWD
      and P index values in comparison with no-statin group (41.7+/-12.2 vs 48.7+/-15.2
      ms, p=0.01, and 14.2+/-3.7 vs 16.5+/-5.3 ms, p=0.02, respectively). CONCLUSIONS:
      Our results show lower PWD values in cryptogenic stroke patients previously
      treated with statins. These findings provide support to the hypothesis that
      statins may play a role in modulating atrial electrophysiological and structural
      properties, preventing the occurrence of a slowed and heterogeneous atrial
      conduction and finally, reducing the occurrence of AF.

PMID- 29332604
TI  - The effect of an adenosine A2A agonist on intra-tumoral concentrations of
      temozolomide in patients with recurrent glioblastoma.
AB  - BACKGROUND: The blood-brain barrier (BBB) severely limits the entry of
      systemically administered drugs including chemotherapy to the brain. In rodents,
      regadenoson activation of adenosine A2A receptors causes transient BBB disruption
      and increased drug concentrations in normal brain. This study was conducted to
      evaluate if activation of A2A receptors would increase intra-tumoral temozolomide
      concentrations in patients with glioblastoma. METHODS: Patients scheduled for a
      clinically indicated surgery for recurrent glioblastoma were eligible.
      Microdialysis catheters (MDC) were placed intraoperatively, and the positions
      were documented radiographically. On post-operative day #1, patients received
      oral temozolomide (150 mg/m2). On day #2, 60 min after oral temozolomide,
      patients received one intravenous dose of regadenoson (0.4 mg). Blood and MDC
      samples were collected to determine temozolomide concentrations. RESULTS: Six
      patients were enrolled. Five patients had no complications from the MDC placement
      or regadenoson and had successful collection of blood and dialysate samples. The
      mean plasma AUC was 16.4 +/- 1.4 h ug/ml for temozolomide alone and 16.6 +/- 2.87
      h ug/ml with addition of regadenoson. The mean dialysate AUC was 2.9 +/- 1.2 h
      ug/ml with temozolomide alone and 3.0 +/- 1.7 h ug/ml with regadenoson. The mean
      brain:plasma AUC ratio was 18.0 +/- 7.8 and 19.1 +/- 10.7% for temozolomide alone
      and with regadenoson respectively. Peak concentration and Tmax in brain were not
      significantly different. CONCLUSIONS: Although previously shown to be efficacious
      in rodents to increase varied size agents to cross the BBB, our data suggest that
      regadenoson does not increase temozolomide concentrations in brain. Further
      studies exploring alternative doses and schedules are needed; as transiently
      disrupting the BBB to facilitate drug entry is of critical importance in neuro
      oncology.

PMID- 29332605
TI  - Antidepressant use during pregnancy and risk of autism spectrum disorder and
      attention deficit hyperactivity disorder: systematic review of observational
      studies and methodological considerations.
AB  - BACKGROUND: Antidepressant exposure during pregnancy has been associated with an
      increased risk of autism spectrum disorder (ASD) and attention deficit
      hyperactivity disorder (ADHD) in several observational studies. We performed a
      systematic review of these studies to highlight the effect that important
      methodological limitations have on such analyses and to consider approaches to
      the conduct, reporting and interpretation of future studies. METHODS: A review of
      MEDLINE and EMBASE identified case-control, cohort and sibling studies assessing
      the risk of ASD and ADHD with antidepressant use during pregnancy. Approaches to
      confounding adjustment were described. Crude and adjusted effect estimates for
      comparisons between antidepressant exposure during pregnancy vs. all unexposed
      women were first meta-analysed using a generic inverse variance method of
      analysis, followed by effect estimates for alternative pre-selected comparison
      groups. RESULTS: A total of 15 studies measuring ASD as an outcome (involving
      3,585,686 children and 40,585 cases) and seven studies measuring ADHD as an
      outcome (involving 2,765,723 patients and 52,313 cases) were identified.
      Variation in confounding adjustment existed between studies. Updated effect
      estimates for the association between maternal antidepressant exposure during
      pregnancy vs. all unexposed women remained statistically significant for ASD
      (adjusted random-effects risk ratio [RaRR] 1.53, 95% confidence interval [CI]
      1.31-1.78). Similar significant associations were observed using pre-pregnancy
      maternal antidepressant exposure (RaRR 1.48, 95% CI 1.29-1.71) and paternal
      antidepressant exposure during pregnancy (1.29, 95% CI 1.08-1.53), but analyses
      restricted to using women with a history of affective disorder (1.18, 95% CI 0.91
      1.52) and sibling studies (0.96, 95% CI 0.65-1.42) were not statistically
      significant. Corresponding associations for risk of ADHD with exposure were: RaRR
      1.38, 95% CI 1.13-1.69 (during pregnancy), RaRR 1.38, 95% CI 1.14-1.69 (during
      pre-pregnancy), RaRR 1.71, 95% CI 1.31-2.23 (paternal exposure), RaRR 0.98, 95%
      CI 0.77-1.24 (women with a history of affective disorder) and RaRR 0.88, 95% CI
      0.70-1.11 (sibling studies). CONCLUSIONS: Existing observational studies
      measuring the risk of ASD and ADHD with antidepressant exposure are heterogeneous
      in their design. Classical comparisons between exposed and unexposed women during
      pregnancy are at high risk of residual confounding. Alternative comparisons and
      sibling designs may aid the interpretation of causality and their utility
      requires further evaluation, including understanding potential limitations of
      undertaking meta-analyses with such data.

PMID- 29332607
TI  - The role of T2*-weighted gradient echo in the diagnosis of tumefactive
      intrahepatic extramedullary hematopoiesis in myelodysplastic syndrome and diffuse
      hepatic iron overload: a case report and review of the literature.
AB  - BACKGROUND: Extramedullary hematopoiesis is the proliferation of hematopoietic
      cells outside bone marrow secondary to marrow hematopoiesis failure.
      Extramedullary hematopoiesis rarely presents as a mass-forming hepatic lesion; in
      this case, imaging-based differentiation from primary and metastatic hepatic
      neoplasms is difficult, often leading to biopsy for definitive diagnosis. We
      report a case of tumefactive hepatic extramedullary hematopoiesis in the setting
      of myelodysplastic syndrome with concurrent hepatic iron overload, and the role
      of T2*-weighted gradient-echo magnetic resonance imaging in differentiating
      extramedullary hematopoiesis from primary and metastatic hepatic lesions. To the
      best of our knowledge, T2*-weighted gradient-echo evaluation of extramedullary
      hematopoiesis in the setting of diffuse hepatic hemochromatosis has not been
      previously described. CASE PRESENTATION: A 52-year-old white man with
      myelodysplastic syndrome and marrow fibrosis was found to have a 4 cm hepatic
      lesion on ultrasound during workup for bone marrow transplantation. Magnetic
      resonance imaging revealed diffuse hepatic iron overload and non-visualization of
      the lesion on T2* gradient-echo sequence suggesting the presence of iron
      deposition within the lesion similar to that in background hepatic parenchyma.
      Subsequent ultrasound-guided biopsy of the lesion revealed extramedullary
      hematopoiesis. Six months later, while still being evaluated for bone marrow
      transplant, our patient was found to have poor pulmonary function tests. Follow
      up computed tomography angiogram showed a mass within his right main pulmonary
      artery. Bronchoscopic biopsy of this mass once again revealed extramedullary
      hematopoiesis. He received radiation therapy to his chest. However, 2 weeks
      later, he developed mediastinal hematoma and died shortly afterward, secondary to
      respiratory arrest. CONCLUSIONS: Mass-forming extramedullary hematopoiesis is
      rare; however, our report emphasizes that it needs to be considered in the
      initial differential diagnosis of hepatic lesions arising in the setting of bone
      marrow disorders. We also show that in the setting of diffuse hepatic iron
      overload, tumefactive extramedullary hematopoiesis appeared isointense to
      background liver on T2* gradient-echo sequence, while adenoma, hepatoma, and
      hepatic metastasis appear hyperintense. Thus, T2*-weighted gradient-echo sequence
      may have a potential role in the imaging diagnosis of mass-forming hepatic
      extramedullary hematopoiesis arising in the setting of diffuse iron overload.

PMID- 29332606
TI  - Tricuspid flow and regurgitation in congenital heart disease and pulmonary
      hypertension: comparison of 4D flow cardiovascular magnetic resonance and
      echocardiography.
AB  - BACKGROUND: Tricuspid valve (TV) regurgitation (TR) is a common complication of
      pulmonary hypertension and right-sided congenital heart disease, associated with
      increased morbidity and mortality. Estimation of TR severity by echocardiography
      and conventional cardiovasvular magnetic resonance (CMR) is not well validated
      and has high variability. 4D velocity-encoded (4D-flow) CMR was used to measure
      tricuspid flow in patients with complex right ventricular (RV) geometry and
      varying degrees of TR. The aims of the present study were: 1) to assess accuracy
      of 4D-flow CMR across the TV by comparing 4D-flow CMR derived TV effective flow
      to 2D-flow derived effective flow across the pulmonary valve (PV); 2) to assess
      TV 4D-flow CMR reproducibility, and 3) to compare TR grade by 4D-flow CMR to TR
      grade by echocardiography. METHODS: TR was assessed by both 4D-flow CMR and
      echocardiography in 21 healthy subjects (41.2 +/- 10.5 yrs., female 7 (33%)) and
      67 RV pressure-load patients (42.7 +/- 17.0 yrs., female 32 (48%)). The CMR
      protocol included 4D-flow CMR measurement across the TV, 2D-flow measurement
      across the PV and conventional planimetric measurements. TR grading on
      echocardiographic images was performed based on the international
      recommendations. Bland-Altman analysis and intra-class correlation coefficients
      (ICC) were used to asses correlations and agreement. RESULTS: TV effective flow
      measured by 4D-flow CMR showed good correlation and agreement with PV effective
      flow measured by 2D-flow CMR with ICC = 0.899 (p < 0.001) and mean difference of 
      1.79 ml [limits of agreement -20.39 to 16.81] (p = 0.084). Intra-observer
      agreement for effective flow (ICC = 0.981; mean difference - 1.51 ml [-12.88 to
      9.86]) and regurgitant fraction (ICC = 0.910; mean difference 1.08% [-7.90;
      10.06]) was good. Inter-observer agreement for effective flow (ICC = 0.935; mean
      difference 2.12 ml [-15.24 to 19.48]) and regurgitant fraction (ICC = 0.968; mean
      difference 1.10% [-7.96 to 5.76]) were comparable. In 25/65 (38.5%) TR grade
      differed by at least 1 grade using 4D-flow CMR compared to echocardiography.
      CONCLUSION: TV effective flow derived from 4D-flow CMR showed excellent
      correlation to PV effective flow derived from 2D-flow CMR, and was reproducible
      to measure TV flow and regurgitation. Twenty-five out of 65 patients (38.5%) were
      classified differently by at least one TR grade using 4D-flow CMR compared to
      echocardiography.

PMID- 29332608
TI  - Concealed complete response in melanoma patients under therapy with immune
      checkpoint inhibitors: two case reports.
AB  - BACKGROUND: The assessment of tumor size by RECIST using CT scans and MRIs is
      considered to be standard of care for staging cancer patients. Despite radiologic
      evidence of widespread disease, we document for the first time that patients were
      completely free of viable tumor. CASE PRESENTATION: Two patients with metastatic
      melanoma were treated with immune checkpoint inhibitors (ipilimumab/ nivolumab)
      and progressive metastases were detected on CT-scans performed shortly before
      histologic examinations. In both patients histologic assessment revealed a
      complete response with necrotic and scarred lesions free of tumor. One of the
      patients had started immunotherapy 20 months before with an initial partial
      response. CONCLUSIONS: This phenomenon of a concealed complete response can lead
      to overtreatment or unnecessary change in treatment. Thus, it is essential to
      raise awareness for it. Correct identification of responders to immune checkpoint
      inhibitor therapy is crucial to spare patients immune-mediated side effects and
      unnecessary as well as expensive treatment. Regression of metastases without
      decline in size, in these cases manifesting as complete responses, are probably
      more common than expected and identified to date. Until such responses can be
      readily identified by new imaging techniques, we recommend liberal biopsies for
      histologic assessment of progressive metastases in patients during and/or after
      immune checkpoint inhibitor therapy.

PMID- 29332610
TI  - Improvements in the conception rate, milk composition and embryo quality of
      rabbit does after dietary enrichment with n-3 polyunsaturated fatty acids.
AB  - This work attempts to confirm the effect of an enriched diet with n-3
      polyunsaturated fatty acids (PUFA) trying to mitigate the reproductive
      performances issues such as low conception rate of primiparous rabbits. A total
      of 127 does were fed ad libitum throughout their two first cycles with two diets
      with different fat sources: mixed fat in the control and salmon oil in the
      enriched one, with 3.19 g/100 g (n=63 does) and 28.77 g/100 g (n=64 does) of n-3
      of the total fatty acid, respectively. Feed intake was similar between groups
      (P>0.05). Plasma progesterone concentration was higher in the enriched females
      than in control ones at 7 (30.9+/-2.18 v. 23.9+/-2.30 ng/ml, respectively;
      P=0.029) and 14 (38.7+/-2.18 v. 28.2+/-2.30 ng/ml, respectively; P=0.001) days of
      first gestation. Considering both cycles, reproductive parameters of mothers
      (fertility, duration of gestation and prolificacy) and litter parameters (weight
      at parturition and weaning, mortality and average daily gain (ADG) of kits during
      lactation) were similar in both groups. However, individual measurements of
      neonates of enriched group improved 5.87%, 7.10% and 18.01% (P0.05), but embryo
      apoptosis rate was higher in control group than in enriched one (31.1+/-4.56% v.
      17.1+/-3.87%, respectively; P<0.05). In conclusion, dietary PUFA enrichment from
      the rearing and throughout two productive cycles improved plasma progesterone
      during pregnancy, fertility, milk fatty acid profile and neonates development of
      primiparous supporting the beneficial effect of n-3 PUFA supplementation in
      rabbit does.

PMID- 29332609
TI  - Investigation of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and
      mean platelet volume in patients with tinnitus.
AB  - OBJECTIVE: This study aimed to evaluate patients with tinnitus in terms of mean
      platelet volume and platelet distribution width, and to explore neutrophil-to
      lymphocyte ratio and platelet-to-lymphocyte ratio, recently reported in the
      literature as being possible inflammation markers. METHODS: This study comprised
      64 tinnitus patients and 64 age-matched healthy controls. Statistical
      significance level was accepted as p < 0.05. RESULTS: Mean platelet volume (t =
      3.245, p = 0.002) and platelet distribution width (Z = 3.945, p < 0.001) were
      significantly higher in the patient group than the control group. CONCLUSION: The
      results suggest that a prothrombotic condition might play a role in the
      pathophysiology of tinnitus.

PMID- 29332611
TI  - Effect of rubber mats and perforation in the lying area on claw and limb lesions
      of fattening pigs.
AB  - Claw and leg lesions are frequently observed in finishing pigs and are likely to
      compromise their welfare. Providing softer than the usual concrete flooring may
      reduce both the frequency and severity of these lesions. Therefore, this study
      evaluated the influence of rubber mats and floor perforation in the lying area on
      claw and leg health of finishing pigs. A total of 240 Swiss Large White finishing
      pigs from on average 24.9 kg until 102.3 kg were used in four batches, with six
      groups of 10 animals per batch. The six experimental pens initially measured
      1.85*3.55 m and were enlarged after 6 weeks to 1.85*5.25 m. In all pens, one
      third of the floor space was built as a defecating area consisting of a concrete
      floor with 15% perforation. The remaining two thirds of the pen were designed as
      a lying area whose floor quality differed between the pens. It either consisted
      of concrete elements or was covered with rubber mats, and perforation of both
      floor types was either 0%, 5% or 10%. All individuals were scored for claw and
      leg lesions at the beginning, in the middle and at the end of the 12-week
      fattening period. Lesions were summarised in scores based on the results of a
      principal component analysis. The influence on lesion scores of floor material,
      amount of perforation in the lying area, assessment time, and sex was examined
      using mixed-models. The total claw lesion score and the total limb lesion score
      as well as the claw angle increased from the beginning to the end of the
      fattening period. The values for both scores were slightly lower for animals kept
      on rubber mats compared with animals kept on concrete floor. There was no effect
      of the percentage of perforation on the examined outcome variables. In
      conclusion, our results indicate that rubber mats in the lying area bring about
      improvements in some aspects of claw and leg health in fattening pigs, whereas
      there is no effect of floor perforation.

PMID- 29332612
TI  - A Colonization Outbreak of Penicillin-Susceptible mecA-Positive Staphylococcus
      aureus in a Neonatal Ward of Children's Hospital.

PMID- 29332613
TI  - Should we tax unhealthy food and drink?
AB  - The global burden of obesity leads to significant morbidity and has major
      economic implications. In April 2018, Britain will join a growing number of
      countries attempting to tackle this using fiscal measures when the UK Soft Drinks
      Industry Levy is introduced. We review recent evidence from natural experiments
      of the impact of health-related food and drink taxes on consumer behaviour, and
      discuss the possible consequences of these approaches on purchases and health. We
      highlight some of the potential indirect consequences and the importance of
      robust prospective evaluation.

PMID- 29332614
TI  - Serelaxin for infant heart failure in congenital dilated cardiomyopathy.
AB  - Serelaxin has been studied in trials in adults with acute heart failure, but not
      in children. We report the first compassionate use of serelaxin in an infant. A 6
      month-old girl with dilated cardiomyopathy was placed on extracorporeal membrane
      oxygenation following cardiac arrest unresponsive to medical treatment.
      Extracorporeal membrane oxygenation weaning failed despite maximal ino-dilator
      therapy. During the 48-hour infusion of serelaxin, we observed marked improvement
      in brain natriuretic peptide, left ventricular systolic function, and dilatation.
      The patient was successfully weaned from extracorporeal membrane oxygenation 24
      hours later. The child died after a second extracorporeal membrane oxygenation
      run owing to sepsis.

PMID- 29332615
TI  - HIV EPIDEMIC HETEROGENEITY IN ZIMBABWE: EVIDENCE FROM SUCCESSIVE DEMOGRAPHIC AND
      HEALTH SURVEYS.
AB  - Zimbabwe has one of the worst HIV epidemics in the world. This study investigated
      data from two successive Zimbabwe Demographic and Health Surveys (ZDHS) conducted
      in 2005-06 and 2010-11. A random representative sample of 30,000 men aged 15-59
      and women aged 15-49 was selected from the two surveys. The HIV prevalence was
      mapped with a flexible, coherent regression framework using a geo-additive semi
      parametric mixed model. HIV indicator prevalence maps were constructed at the
      regional level, and at the administrative level relevant for policy design,
      planning and decision-making. Substantial regional variation was found, not only
      in the burden of HIV, but also in its risk factors. The results suggest that
      responses/policies should vary at the regional level to ensure that the often
      diverse needs of populations across a country are met and incorporated into
      planning the HIV response. The use of geographically referenced data in two
      successive ZDHS provides crucial new insights into the spatial characteristics of
      the HIV epidemic in Zimbabwe. In particular, it highlights the HIV heterogeneity
      across Zimbabwe, with substantial regional variation, not only in the burden of
      HIV, but also in its risk factors.

PMID- 29332616
TI  - Addressing Children's Needs in Disasters: A Regional Pediatric Tabletop Exercise.
AB  - OBJECTIVE: Preparing and responding to the needs of children during public health
      emergencies continues to be challenging. The purpose of this study was to assess
      the usefulness of a tabletop exercise in initiating pediatric preparedness
      strategies and assessing the impact of the exercise on participants'
      understanding of and confidence in their roles during pediatric public health
      emergencies. METHODS: A tabletop exercise was developed to simulate a public
      health emergency scenario involving smallpox in a child, with subsequent spread
      to multiple states. During the exercise, participants discussed and developed
      communication, collaboration, and medical countermeasure strategies to enhance
      pediatric public health preparedness. Exercise evaluation was designed to assess
      participants' knowledge gained and level of confidence surrounding pediatric
      public health emergencies. RESULTS: In total, 22 participants identified over 100
      communication and collaboration strategies to promote pediatric public health
      preparedness during the exercise and found that the most beneficial aspect during
      the exercise was the partnership between pediatricians and public health
      officials. Participants' knowledge and level of confidence surrounding a
      pediatric public health emergency increased after the exercise. CONCLUSION: The
      tabletop exercise was effective in identifying strategies to improve pediatric
      public health preparedness as well as enhancing participants' knowledge and
      confidence surrounding a potential pediatric public health emergency. (Disaster
      Med Public Health Preparedness. 2018;12:582-586).

PMID- 29332617
TI  - Decontamination of Extracorporeal Membrane Oxygenator Devices With an Intensified
      Disinfection Protocol: How Strict Is Too Strict?

PMID- 29332618
TI  - Online market research panel members as controls in case-control studies to
      investigate gastrointestinal disease outbreaks: early experiences and lessons
      learnt from the UK.
AB  - Established methods of recruiting population controls for case-control studies to
      investigate gastrointestinal disease outbreaks can be time consuming, resulting
      in delays in identifying the source or vehicle of infection. After an initial
      evaluation of using online market research panel members as controls in a case
      control study to investigate a Salmonella outbreak in 2013, this method was
      applied in four further studies in the UK between 2014 and 2016. We used data
      from all five studies and interviews with members of each outbreak control team
      and market research panel provider to review operational issues, evaluate risk of
      bias in this approach and consider methods to reduce confounding and bias. The
      investigators of each outbreak reported likely time and cost savings from using
      market research controls. There were systematic differences between case and
      control groups in some studies but no evidence that conclusions on the likely
      source or vehicle of infection were incorrect. Potential selection biases
      introduced by using this sampling frame and the low response rate are unclear.
      Methods that might reduce confounding and some bias should be balanced with
      concerns for overmatching. Further evaluation of this approach using comparisons
      with traditional methods and population-based exposure survey data is
      recommended.

PMID- 29332620
TI  - CJEM Debate Series: #Copayment - Medical insurance is for non-routine events.

PMID- 29332621
TI  - A New Chapter for CJEM.

PMID- 29332619
TI  - Clinical characteristics of non-tuberculous mycobacterial pulmonary infections in
      Bamako, Mali.
AB  - The global spread of non-tuberculous mycobacteria (NTM) may be due to HIV/AIDS
      and other environmental factors. The symptoms of NTM and tuberculosis (TB)
      disease are indistinguishable, but their treatments are different. Lack of
      research on the epidemiology of NTM infections has led to underestimation of its
      prevalence within TB endemic countries. This study was designed to determine the
      prevalence and clinical characteristics of pulmonary NTM in Bamako. A cross
      sectional study which include 439 suspected cases of pulmonary TB. From 2006 to
      2013 a total of 332 (76%) were confirmed to have sputum culture positive for
      mycobacteria. The prevalence of NTM infection was 9.3% of our study population
      and 12.3% of culture positive patients. The seroprevalence of HIV in NTM group
      was 17.1%. Patients who weighed <55 kg and had TB symptoms other than cough were
      also significantly more likely to have disease due to NTM as compared to those
      with TB disease who were significantly more likely to have cough and weigh more
      than 55 kg (OR 0.05 (CI 0.02-0.13) and OR 0.32 (CI 0.11-0.93) respectively). NTM
      disease burden in Bamako was substantial and diagnostic algorithms for pulmonary
      disease in TB endemic countries should consider the impact of NTM.

PMID- 29332623
TI  - Gene expression and lymphocyte population at the fetal-maternal interface in
      sheep pregnancies established by somatic cell nuclear transfer.
AB  - The hypothesis of this study was that the leukocyte populations and expression
      levels of genes related to immune response, growth factors and apoptosis would be
      altered at the fetal-maternal interface in somatic cell nuclear transfer (SCNT)
      generated sheep pregnancies. Placental and endometrial samples from sheep
      pregnancies established by SCNT and natural breeding (control) were collected at
      45 days and at term. Expression of genes related to growth factors, apoptosis and
      immune response was examined using quantitative reverse transcription polymerase
      chain reaction. Endometrial leukocyte populations and major histocompatibility
      class I (MHC-I) protein expression were examined by immunohistochemistry. At term
      we observed altered expression of genes related to apoptosis, growth factors and
      immune response in placental and endometrial tissue of SCNT pregnancies. In Day
      45 pregnancies there was less-pronounced abnormal expression and only genes
      related to apoptosis and growth factors were abnormal in the placenta.
      Endometrial gene expression profiles were similar to age-matched controls.
      Placental MHC-I protein expression was similar in SCNT and controls at 45 days
      but increased in the SCNT at term. The altered gene expression at the fetal
      maternal interface likely contributes to the placental dysfunction and overgrowth
      observed in sheep SCNT pregnancies.

PMID- 29332622
TI  - In vivo and in vitro strategies to support caprine preantral follicle development
      after ovarian tissue vitrification.
AB  - The aim of the present study was to compare fresh and vitrified goat ovarian
      tissue after autotransplantation and in vitro culture. Adult goats were
      completely ovariectomised and each ovarian pair was sliced and distributed among
      six different treatment groups: fresh control, fresh transplant, fresh culture,
      vitrified control, vitrified transplant and vitrified culture. Follicular
      morphology, development, growth, density, revascularisation and hormone
      production were evaluated in all groups. Three antral follicles (two in the fresh
      transplant and one in the vitrified transplant groups) were observed on the
      surface of the graft 90 days after transplantation. The percentage of
      morphologically normal follicles was similar in the fresh control, fresh
      transplant and vitrified transplant groups. The percentage of developing
      (transition, primary and secondary) follicles was higher after in vitro culture
      of fresh or vitrified tissue. Transplantation resulted in a lower follicle
      density. Serum oestradiol concentrations remained constant during the entire
      transplantation period. In contrast, progesterone production decreased
      significantly. Expression of CD31 mRNA was lower in fresh culture. In conclusion,
      restoration of goat ovarian function can be successfully achieved following
      transplantation of both fresh and vitrified goat ovarian tissue. However,
      transplantation induced higher follicle loss than in vitro culture.

PMID- 29332624
TI  - [Not all exacerbations of chronic obstructive pulmonary disease should be treated
      with antibiotics].
AB  - This review gives an update on antibiotic treatment of exacerbation of chronic
      obstructive pulmonary disease (COPD). Patients who do not need hospital admission
      and do not present with purulent sputum nor increased levels of C reactive
      protein/procalcitonin have no beneficial effect of antibiotic treatment. Those
      with severe COPD and increased sputum purulence should be treated with
      antibiotics, and first-line treatment should be amoxicillin, which is effective
      against the most common types of bacteria in COPD exacerbation. In patients with
      very severe COPD, amoxicillin/clavulanate could also be first-line treatment.

PMID- 29332625
TI  - Positive and negative affect mediate the bidirectional relationship between
      emotional processing and symptom severity and impact in irritable bowel syndrome.
AB  - INTRODUCTION: Individuals with IBS report higher levels of psychological distress
      compared to healthy controls. Distress has been associated with emotional
      processing difficulties but studies have not explored how the relationship
      between distress and emotional processing affects IBS. There is little research
      on the role of positive affect (PA) in IBS. AIMS: (a) If difficulties in self
      reported emotional processing are associated with affect and IBS measures (i.e.,
      symptom severity, interference in life roles) (b1) If affect mediates the
      relationship between emotional processing and IBS measures (b2) Alternative
      model: if affect mediates the relationship between IBS and emotional processing
      (c) If PA moderates the relationship between distress and IBS. METHODS:
      Participants with a confirmed diagnosis of IBS (n=558) completed a questionnaire
      including measures of emotional processing (i.e., unhelpful beliefs about
      negative emotions, impoverished emotional experience), distress, PA, and IBS
      symptoms/interference. Mediation and moderation analyses were conducted with
      Maximum Likelihood Estimation. RESULTS: Distress and PA mediated or partly
      mediated the relationship between unhelpful beliefs about negative
      emotions/impoverished emotional experience and both IBS measures. The alternative
      models were also valid, suggesting a two-way relationship between emotional
      processing and IBS through affect. PA did not moderate the relationship between
      distress and IBS. CONCLUSION: Future interventions in IBS may benefit from not
      only targeting the management of physical symptoms and their daily impact but
      also aspects related to the experience of both negative and positive affect, and
      the acceptance and expression of negative emotions. Longitudinal studies are
      needed to confirm causal relationships within the explored models.

PMID- 29332626
TI  - Symptoms of depression and anxiety and 11-year all-cause mortality in men and
      women undergoing coronary artery bypass graft (CABG) surgery.
AB  - OBJECTIVES: To investigate the overall and the sex-specific association of
      preoperative and one-year post coronary artery bypass (CABG) surgery symptoms of
      depression and anxiety with 11-year all-cause mortality. METHODS: A multicenter
      prospective study including 1125 patients who completed the Hospital Anxiety and
      Depression Scale (HADS) before an elective CABG surgery, of whom 850 completed
      the HADS again at one-year follow-up. Information on all-cause mortality was
      obtained through the Israeli Ministry of Internal Affairs Register. Multivariable
      adjusted Cox regression models quantified the association of symptoms of
      depression and anxiety with all-cause mortality. RESULTS: Females comprised 22.7%
      of the cohort and were 5.5years older than males (70.0+/-9.3 and 64.4+/
      10.3years, respectively). Controlling for sociodemographic and lifestyle factors,
      illness severity and post-surgery participation in cardiac rehabilitation, there
      was little evidence of an association between preoperative symptoms of depression
      and mortality in males [adjusted hazard ratio (aHRmales)=1.03, 95% CI 0.99-1.07,
      p=0.21] or females (aHRfemales=1.01, 95% CI 0.95-1.08, p=0.7). One-year
      postoperative symptoms of depression were associated with mortality in both males
      (aHRmales=1.05, 95% CI 1.01-1.10, p=0.03) and females (aHRfemales=1.07, 95% CI
      1.02-1.13, p=0.013). Preoperative symptoms of anxiety were unrelated to mortality
      overall, but among females postoperative symptoms of anxiety predicted 11-year
      mortality (aHRfemales=1.07, 95% CI 1.00-1.14, p=0.049). There was no HADS by sex
      interaction (p for interaction=0.12-0.99). CONCLUSIONS: Symptoms of depression
      one-year after surgery were positively related to mortality with little evidence
      for sex differences. These findings underscore the need for identification and
      treatment of psychiatric symptoms in patients undergoing CABG surgery. CLINICAL
      TRIAL REGISTRATION: ClinicalTrials.gov: NCT00356863.

PMID- 29332627
TI  - Pre-transplant history of mental health concerns, non-adherence, and post
      transplant outcomes in kidney transplant recipients.
AB  - OBJECTIVE: The association between pre-transplant mental health concerns and non
      adherence and post-transplant outcomes after kidney transplantation is not fully
      established. We examined the relationship between a pre-transplant history of
      mental health concerns and non-adherence and post-transplant outcomes among
      kidney transplant recipients. METHODS: In this retrospective single center cohort
      study of adult kidney transplant recipients (n=955) the associations between the
      history of mental health concerns or non-adherence and the time from kidney
      transplant to biopsy proven acute rejection; death-censored graft failure and
      total graft failure were examined using Cox proportional hazards models. RESULTS:
      Mean (SD) age was 51 (13) years, 61% were male and 27% had a history of diabetes.
      Twenty-two and 11% of patients had mental health concerns and non-adherence,
      respectively. Fifteen percent of the patients had acute rejection, 5.6% had death
      censored graft failure and 13.0% had total graft failure. The history of mental
      health concerns was not associated with acute rejection, death-censored graft
      failure or total graft failure. Patients with versus without a history of non
      adherence tended to have higher cumulative incidence of acute rejection (23.3%
      [95% CI: 16.1, 33.2] vs. 13.6% [95% CI: 11.4, 16.2]) and death-censored graft
      failure (15.0% [95% CI: 6.9, 30.8] vs. 6.4% [95% CI: 4.7, 8.7]) (log rank p=0.052
      and p=0.086, respectively). These trends were not significant after multivariable
      adjustment. CONCLUSION: In summary, a history of pre-transplant mental health
      concerns or non-adherence is not associated with adverse outcomes in patients who
      completed transplant workup and received a kidney transplant.

PMID- 29332628
TI  - Socioeconomic factors in coronary artery disease - Results from the SPIRR-CAD
      study.
AB  - : Low socio-economic status (SES) has been associated with an increased coronary
      risk in Western countries. All stress experiences are more pronounced in low SES
      patients with stress emanating from problems with family, job, or money. The
      SPIRR-CAD study offered an excellent opportunity to examine these risk factors in
      German speaking mildly and medium depressed patients. In the SPIRR CAD study, a
      German multi centre randomized clinical trial of 450 male and 120 female coronary
      patients, we examined the standard and psychosocial risk factor profiles in
      relation to SES, as assessed by educational level. All differences in risk
      factors between low and high SES were in the inverse direction. Of standard risk
      factors, only smoking was socially graded and more common in low SES. Of
      psychosocial factors and emotions, exhaustion showed the strongest and most
      consistent inverse social gradient, but also anger, anxiety and depression were
      socially graded. The findings suggest that in German patients, as in other
      national groups, social gradients in CHD risk are considerable. They can be
      ascribed to both psychosocial and to standard risk factors. In the present two
      years follow-up, the prospective significance of psychological and social risk
      factors was analyzed showing that emotional factors played an important role, in
      that low and high SES patients differed in the expected direction. However, the
      differences were not statistically significant and therefore firm conclusions
      from follow up were not possible. TRIAL REGISTRATION: ISRCTN 76240576;
      NCT00705965.

PMID- 29332629
TI  - Psychobiological stress in vital exhaustion. Findings from the Men Stress 40+
      study.
AB  - OBJECTIVE: Despite the increased risk for cardiovascular morbidity associated
      with vital exhaustion (VE), the underlying pathophysiological mechanisms remain
      unclear. Allostatic load may constitute the missing link between VE and
      cardiovascular diseases. The aim of the present study was to investigate whether
      men with different degrees of VE would differ in terms of allostatic load,
      chronic stress, and social support. METHODS: The Men Stress 40+ study sample
      consisted of N=121 apparently healthy men aged 40 to 75years. The following
      allostatic load markers were aggregated to create a cumulative index of
      biological stress: salivary cortisol, salivary dehydroepiandrosterone sulfate
      (DHEA-S), waist-to-hip-ratio, systolic and diastolic blood pressure. Long-term
      cortisol and DHEA were additionally measured in hair. Chronic stress and social
      support were assessed via validated questionnaires. Groups of mildly,
      substantially, and severely exhausted men were compared using one-way ANOVAs with
      appropriate post-hoc tests. RESULTS: Men who reported mild or severe levels of
      vital exhaustion had the highest scores on the cumulative index of biological
      stress. Hair cortisol was unrelated to vital exhaustion; hair DHEA was highest in
      men with substantial levels of exhaustion. Men with mild exhaustion reported the
      lowest levels of chronic stress, while men with severe exhaustion reported the
      lowest levels of social support. CONCLUSIONS: Signs of allostatic load are
      detectable in vitally exhausted men at a stage where no major cardiovascular
      consequences have yet ensued.

PMID- 29332630
TI  - Effects of a program of cognitive-behavioural group therapy, vestibular
      rehabilitation, and psychoeducational explanations on patients with dizziness and
      no quantified balance deficit, compared to patients with dizziness and a
      quantified balance deficit.
AB  - BACKGROUND: We examined whether a program combining cognitive-behavioural therapy
      (CBT), vestibular rehabilitation (VR) and psychoeducation is equally effective in
      improving psychometric measures in patients with dizziness independent of a
      balance deficit. Measures of patients with dizziness only (DO) were compared to
      those of patients also having a quantified balance deficit (QBD). METHODS: 32
      patients (23 female, 9 male) with persistent dizziness were analysed as 2 groups
      based on stance and gait balance control: those with QBD (pathological balance)
      or DO (normal balance). Dizziness Handicap Inventory (DHI) and Brief Symptom
      Inventory (BSI) questionnaires were used pre- and post-therapy to assess
      psychometric measures. Patients then received the same combination therapy in a
      group setting. RESULTS: The QBD group mean age was 60.6, SD 8.3, and DO group
      mean age 44.8, SD 12.1, years. Pre-therapy, questionnaire scores were
      pathological but not different between groups. Balance improved significantly for
      the QBD group (p=0.003) but not for the DO group. DHI and BSI scores improved
      significantly in the DO group (0.001<p<0.045), some BSI sub-scores reaching
      normal levels. These scores were unchanged for the QBD group. Phobic anxiety
      scores changed most for both groups, being significantly correlated with DHI
      scores, higher (R=0.71 vs. 0.57) for the DO group. CONCLUSIONS: A combination of
      CBT, VR, and psychoeducation improves psychological measures in DO patients but
      not significantly in QBD patients, despite their balance control improving to
      near normal. Possibly, greater focus on phobic anxiety during the group therapy
      program would have improved psychological measures of QBD patient.

PMID- 29332632
TI  - Retrospective memory for symptoms in patients with medically unexplained
      symptoms.
AB  - OBJECTIVE: Clinical assessment and diagnostic processes heavily rely on memory
      based symptom reports. The current study investigated memory for symptoms and the
      peak-end effect for dyspnea in patients with medically unexplained symptoms and
      healthy participants. METHODS: Female patients with medically unexplained dyspnea
      (MUD) (n=22) and matched healthy controls (n=22) participated in two dyspnea
      induction trials (short, long). Dyspnea ratings were collected: (1) continuously
      during symptom induction (concurrent with respiratory measures), (2) immediately
      after the experiment, and (3) after 2weeks. Symptoms, negative affect, and
      anxiety were assessed at baseline and after every trial. The mediating role of
      state anxiety in symptom reporting was assessed. The peak-end effect was tested
      with forced-choice questions measuring relative preference for the trials.
      RESULTS: Compared to controls, dyspnea induction resulted in higher levels of
      symptoms, anxiety, concurrent dyspnea ratings, and minute ventilation in the
      patient group. In both groups, immediate retrospective ratings were higher than
      averaged concurrent ratings. No further increase in dyspnea ratings was observed
      at 2-week recall. Retrospective dyspnea ratings were mediated by both state
      anxiety and concurrent dyspnea ratings. Patients did not show a peak-end effect,
      whereas controls did. CONCLUSION: The findings show that patients' experience of
      a dyspneic episode is subject to immediate memory bias, but does not change over
      a longer time period. The results also highlight the importance of affective
      state during symptom experience for both symptom perception and memory.

PMID- 29332631
TI  - Treatment utilization and barriers to treatment among individuals with olfactory
      reference syndrome (ORS).
AB  - OBJECTIVE: Olfactory reference syndrome (ORS) is characterized by a preoccupation
      that one is emitting a foul or offensive odor. Despite the profound psychosocial
      impact of ORS, many patients do not receive appropriate treatment, and there is
      no empirical research on treatment-seeking behavior in ORS. This study
      investigated treatment utilization patterns and barriers to treatment in
      individuals with ORS. METHOD: 253 subjects completed an online survey between
      January-March 2010. Data were obtained from the Yale-Brown Obsessive Compulsive
      Scale Modified for ORS (ORS-YBOCS), Depression Anxiety Stress Scales (DASS), Work
      and Social Adjustment Scale (WSAS), and questionnaires specific to treatment
      utilization and barriers. RESULTS: The sample was ethnically diverse,
      predominately male (67%), with an average age of 33.7years, and moderately severe
      ORS symptoms. Most participants first sought care from a medical specialist
      (44%), and mental health services were underutilized (14%). Higher functional
      impairment was significantly correlated with seeking care from a mental health
      provider, compared to a medical specialist. Nearly all participants endorsed
      multiple barriers to treatment, including (a) logistical/financial, (b)
      stigma/discrimination, and (c) treatment perception barriers. ORS symptom
      severity was significantly, positively correlated with number of
      logistical/financial and stigma/discrimination barriers. Treatment barriers were
      significantly influenced by ethnic group, ORS symptom severity, and source of
      odor. CONCLUSION: Results highlight the importance of increasing awareness and
      enhancing access to care for individuals with ORS.

PMID- 29332633
TI  - Impact of psychological factors on the health-related quality of life of patients
      treated for pulmonary arterial hypertension.
AB  - OBJECTIVE: Pulmonary arterial hypertension (PAH) is a rare and life-threatening
      disease well-marked by under diagnosis, delayed diagnosis and atypical
      treatments. Few data are available on the quality of life (QoL) and psychosocial
      characteristics of patients with PAH. Our aim is to describe the impact of
      psychological factors on the health-related quality of life (HRQoL) of treated
      PAH patients in a cross-sectional study. METHODS: Consecutive patients presenting
      at our Competency Centre for PAH were recruited. The aetiology, New York Heart
      Association (NYHA) stage, haemodynamics, 6-min walk distance (6MWD), delta SPO2
      (Pulse oximeter oxygen saturation; baseline lowest value during 6-min walk test
      (6MWT), current treatments and psychological history were recorded. HRQoL,
      anxiety, depression and coping strategies were explored using self-administered
      questionnaires (SF-36, HADS, STAI-Y, CHIP and WCC). RESULTS: A total of 55
      patients were included. The HRQoL of PAH patients was poor with altered results
      on several scales. Anxiety and depression were high and coping was focused on
      medical information strategies. Multivariate analysis indicated a positive
      relationship between 6MWD and the Physical Composite Score for QoL (p=0.004), as
      well as a negative relationship between delta SPO2 and the Mental Composite Score
      (p=0.02), irrespective of other known prognostic factors (such as haemodynamics
      at right heart catheterization). Depression and Trait-Anxiety were associated
      with a lower physical (p=0.001) and mental (p<0.001) QoL, respectively.
      CONCLUSIONS: Psychological factors impact the HRQoL of treated patients. A
      longitudinal and qualitative study should refine these results. TRIAL
      REGISTRATION: Clinical trial N degrees : NCT01380054.

PMID- 29332634
TI  - Reports of wheezing and of diagnosed asthma are associated with impaired social
      functioning: Secondary analysis of the cross-sectional World Health Survey data.
AB  - OBJECTIVE: We sought to investigate whether there are associations between asthma
      and social functioning in adults from Western and non-Western countries. METHODS:
      We analyzed data on individuals (94% aged 20+, 52% female) from 50 countries
      participating in the cross-sectional World Health Survey. We used information on
      self-reports of wheezing and an asthma diagnosis. Social functioning was defined
      by reports of severe or extreme difficulties related to personal relationships or
      participation in the community. Logistic regression was used to estimate adjusted
      odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Wheezing was
      associated with impaired social functioning both in the overall sample (OR=2.40,
      95%CI=2.09-2.75) and in Africa, South America and Asia (ORs>=2.47), but not in
      Europe (aOR=1.26, 95%CI=0.90-1.77). Analyses with self-reports of diagnosed
      asthma yielded similar, albeit weaker, associations (e.g. OR for the overall
      sample=1.63, 95%CI=1.38-1.92). We also combined asthma and wheezing into a single
      variable (reference group: no asthma diagnosis/no wheezing). We observed that in
      particular reports of wheezing were associated with impaired social functioning
      regardless of whether a concomitant asthma diagnosis was reported (OR=2.19,
      95%CI=1.81-2.64) or not (OR=2.50, 95%CI=2.09-2.99). CONCLUSION: Self-reports of
      wheezing and of diagnosed asthma are associated with impaired social functioning
      among adults in Africa, South America and Asia, but less so in Europe. These
      relationships are mainly driven by the experience of respiratory symptoms (i.e.
      wheezing). Our findings may partly be explained by regional variations in asthma
      control. Further research should elucidate the determinants and mechanisms of
      asthma-related impaired social functioning.

PMID- 29332635
TI  - Fear of hypoglycemia in patients with type 2 diabetes: The role of interoceptive
      accuracy and prior episodes of hypoglycemia.
AB  - OBJECTIVE: Fear of hypoglycemia (FoH) is a limiting factor for diabetes self
      management and can have detrimental effects on quality of life. However,
      relatively little is known about its underlying mechanisms. In line with findings
      on patients with anxiety disorders, we hypothesized that interoceptive accuracy
      (IA) might be positively linked to FoH in patients with type 2 diabetes (T2DM).
      METHODS: 133 patients with T2DM were screened according to the extreme quartiles
      of the Hypoglycemia Fear Survey worry subscale (HFS-W). Overall, 66 participants
      (HFS-W<4; HFS-W>17) were included in the present study. Participants completed
      questionnaires on sociodemographic and diabetes-related measures. Accuracy of
      heartbeat perception was assessed using the mental tracking task. RESULTS:
      Contrary to expectations, IA did not differ significantly between patients with
      low and high FoH. A linear regression analysis demonstrated that the experience
      of mild hypoglycemia (beta=0.32, p<=0.01) and its interaction with IA (beta=
      0.26, p=0.040) were significant predictors of FoH, indicating that low IA and a
      history of experiencing mild hypoglycemia are positively associated with FoH.
      CONCLUSION: Our findings suggest a positive association of low IA in combination
      with prior episodes of hypoglycemia and FoH in patients with T2DM. The results
      are in line with recent findings on IA in patients with chronic somatic symptom
      distress more generally and contribute to our understanding of the relations
      between interoception, body related fears, and physical symptom perception.

PMID- 29332636
TI  - Implementation of an electronic routine outcome monitoring at an inpatient unit
      for psychosomatic medicine.
AB  - BACKGROUND: Patient-reported outcomes (PROs) can be part of an electronic routine
      outcome monitoring (eROM). eROM can improve patient involvement, treatment
      outcomes and simplify scientific data assessment. Available studies on eROM focus
      on its evaluation only and lack a detailed description of the prior
      implementation procedure. OBJECTIVE: The aim was to implement an eROM assessment
      at a division of Psychosomatic Medicine and provide a detailed description of the
      implementation procedure. METHODS: According to the Replicating Effective Program
      concept the project consisted of 4 phases: pre-condition (1), pre-implementation
      (2), implementation (3) and maintenance and evolution (4) mainly focusing the
      description of the implementation procedure and a short evaluation. RESULTS: We
      describe the actions taken during the implementation procedure and steps which
      were taken to overcome identified barriers. All decisions were carried out based
      on the Participatory Action Research process. A core set consisting of
      sociodemographic and clinical data and a comprehensive questionnaire battery
      covering symptoms, functioning parameters and psychological constructs was
      implemented. In total 164 patients, took part in the eROM assessment from June
      2015 to December 2016. The evaluation showed that eROM was appreciated by health
      care professionals (85.2%) and patients (70.2%) alike. The majority of patients
      (89.4%) and health-care professionals (85.7%) experienced no delays in daily
      clinical routine due to eROM. CONCLUSION: The detailed description of the
      implementation process can guide institutions planning to implement eROM into
      their daily clinical routine. Focusing scientific efforts on the implementation
      process is essential since this influences all further steps such as evaluation
      and acceptance.

PMID- 29332637
TI  - Pilot-RCT of an integrative group therapy for patients with refractory irritable
      bowel syndrome (ISRCTN02977330).
AB  - OBJECTIVE: Different forms of psychotherapeutic treatments have been proven
      effective in irritable bowel syndrome (IBS), but disorder-oriented and
      integrative concepts are still rare. Therefore, we implemented and evaluated an
      integrative group therapeutic concept within an interdisciplinary tertiary care
      clinic for functional gastrointestinal disorders (FGIDs). AIMS: present our
      integrative group concept, assess feasibility issues, and evaluate efficacy.
      METHODS: A pilot-RCT with a randomized controlled wait-listed group design was
      conducted. The treatment concept was a disorder-oriented multicomponent group
      therapy (12 90-min weekly sessions) integrating interactive psychoeducation, gut
      directed hypnotherapy, and open group phases. All patients received enhanced
      medical care and completed a short online diary as an active wait-listed control
      condition. INCLUSION CRITERIA: refractory IBS diagnosed as somatoform autonomic
      dysfunction of the lower gastrointestinal tract (SAD). PRIMARY OUTCOME: IBS
      symptom severity (IBS-SSS). RESULTS: Of 294 patients, 220 had IBS (ROME III), 144
      were diagnosed as SAD (ICD-10), 51 were eligible regarding inclusion/exclusion
      criteria, and 30 consented to participate (group intervention: n=16, wait-listed
      control condition: n=14). Only 1 patient dropped out. Intention-to-treat-analysis
      with repeated-measures mixed ANOVA showed that the group intervention was not
      significantly superior to the wait-listed control condition. Nevertheless, the
      calculated effect size for the between-group difference in IBS-SSS at the end of
      treatment (post) was moderate (d=0.539). CONCLUSION: Our disorder-oriented
      integrative group intervention for IBS proved to be acceptable and feasible in an
      interdisciplinary tertiary care setting. There is promise in this intervention,
      but a larger RCT may be needed to investigate efficacy.

PMID- 29332638
TI  - The effect of exercise therapy on depressive and anxious symptoms in patients
      with ischemic heart disease: A systematic review.
AB  - OBJECTIVE: Depressive and anxiety symptoms are associated with Ischemic Heart
      Disease (IHD). Exercise interventions might improve both depressive and anxiety
      symptoms, but an overview of the evidence is lacking. Therefore, we
      systematically reviewed the existing literature on the effectiveness of exercise
      therapy to reduce depression and anxiety symptoms specifically in patients with
      IHD. METHODS: MEDLINE, EMBASE, PsycINFO and the Cochrane Central Register of
      Controlled Trials were searched until January 2016. The effectiveness of exercise
      was assessed within two groups: a) patients selected for study with severe
      depression or anxiety; and b) studies that did not exclusively targeted patients
      with increased levels of depression or anxiety. Secondary outcomes were
      mortality, cardiac events, re-hospitalizations and cardiovascular risk factors.
      RESULTS: We included fourteen studies. Clinical and methodological heterogeneity
      precluded meta-analysis. Three studies specifically included patients with high
      levels of depression or anxiety and eleven studies selected patients with unclear
      levels of depression or anxiety. Some RCTs showed that exercise was effective in
      lowering severe depressive symptoms (short and long term follow-up), but for the
      group with unclear depressive symptoms the results were non-conclusive. In the
      group with elevated anxiety symptoms, exercise had a positive effect on the short
      term follow-up. In the group with unclear anxiety symptoms the results were
      inconsistent (short and long term follow-up). No differences were found regarding
      the secondary outcomes. CONCLUSIONS: There is a general paucity of data on the
      effect of exercise, precluding firm conclusions about the effectiveness of
      exercise for depressive and anxiety symptoms in IHD patients.

PMID- 29332639
TI  - Genetic and environmental influences to low back pain and symptoms of depression
      and anxiety: A population-based twin study.
AB  - BACKGROUND: People suffering from chronic pain are more likely to experience
      symptoms of depression and anxiety. However, the mechanisms underlying this
      relationship remain largely unknown. In light of the moderate to large effects of
      genetic factors on chronic pain and depression and anxiety, we aimed to estimate
      the relative contribution of genetic and environmental factors to the
      relationship between these traits. METHODS: Using data from 2139 participants in
      the Murcia Twin Registry, we employed a bivariate analysis and structural
      equation modeling to estimate the relative influences of genetics and the
      environment on the covariation between low back pain and symptoms of depression
      and anxiety. RESULTS: We have obtained heritability estimates of 0.26 (95%
      Confidence Interval (CI) 0.11, 0.41) for chronic low back pain and 0.45 (95% CI
      0.29, 0.50) for symptoms of depression and anxiety. The phenotypic, genetic, and
      unique environment correlations in the bivariate analytical model were,
      respectively, rph=0.26 (95% CI 0.19, 0.33); rG=0.47 (95% CI 0.42, 0.70); rE=0.14
      (95% CI -0.04, 0.25). The percentage of covariance between low back pain and
      symptoms of depression and anxiety attributable to additive genetic factors was
      63.6%, and to unique environment 36.4%. CONCLUSIONS: Our findings confirm the
      relationship between low back pain and symptoms of depression and anxiety in a
      non-clinical sample. Shared genetic factors affect significantly the covariation
      between these conditions, supporting the role of common biological and
      physiological pathways.

PMID- 29332640
TI  - Cognitive impairment in patients with psoriasis: A matched case-control study.
AB  - BACKGROUND: In the past decade, a few studies have suggested that psoriasis could
      be associated with the presence of mild cognitive deficits. OBJECTIVES: The aim
      of the present matched case-control study was to investigate several cognitive
      domains (executive functions, verbal memory, attention, and language) in a sample
      of outpatients with psoriasis. We also investigated whether cognitive impairment
      was associated with poor health-related quality of life (HRQoL) in patients with
      psoriasis. METHODS: Fifty adult outpatients and 50 age- and sex-matched healthy
      controls were administered a battery of neuropsychological tests investigating
      major cognitive domains, psychopathology (anxiety and depression), alexithymia,
      and HRQoL. RESULTS: At the bivariate level, psoriasis patients (compared to
      healthy controls) performed worse on most of the neuropsychological tests, and
      they also reported more anxiety and depressive symptoms, higher scores for
      alexithymia, and worse physical and mental health. At the multivariate level,
      cognitive performance was independently associated with psoriasis even when
      controlling for psychopathology and alexithymia. CONCLUSIONS: Patients with
      psoriasis show impaired cognitive performance, high levels of anxiety and
      depression, and impaired quality of life. Based on the current results,
      clinicians should assess the presence of psychological symptoms in their patients
      and evaluate whether the presence of cognitive deficits is limiting the patients'
      ability to cope with the disease.

PMID- 29332641
TI  - Epidemiological paradigm: Tuberculosis in HIV, diabetes, and smoking in North
      East India: An impact greater than sum of its parts.

PMID- 29332642
TI  - Current Affairs, Future Perspectives of Tuberculosis and Antitubercular Agents.
AB  - Tuberculosis (TB) is the major threat for humans from past several decades. Even
      after advent of several antitubercular drugs, researchers are still struggling
      for the mycobacterial infections in humans are TB and leprosy. Chronic infections
      caused by Mycobacterium tuberculosis and Mycobacterium leprae. A particular
      problem with both of these organisms is that they can survive inside macrophages
      after phagocytosis, unless these cells are activated by cytokines produced by T
      lymphocytes, because of this researchers are not yet succeeded in finding
      effective treatment on TB. In recent years TB has spread globally and became the
      major issue for world healthcare organizations. Some compounds like
      benzothiazinones shown promising activity against mycobacterium, few compounds
      are in pipeline which may exhibit improved pharmacological effect.
      Decaprenylphosphoryl-d-ribose 2'-epimerase (DprE1) is the vulnerable target for
      antitubercular drug discovery. DprE1 is a flavoprotein that along with
      decaprenylphosphoryl-2-keto-ribose reductase catalyses epimerization of
      decaprenylphosphoryl-d-ribose to decaprenylphosphoryl-d-arabinose through an
      intermediate formation of decaprenylphosphoryl-2-keto-ribose. This conversion
      makes DprE1 a potential drug target. Further research requires to tackle the
      biggest hurdles in Tuberculosis treatment, i.e. multi drug and extensively drug
      resistance.

PMID- 29332643
TI  - Role of laparoscopy in diagnosing genital tuberculosis in suspected women: A
      cross-sectional study from a tertiary care hospital in Northern India.
AB  - This study was included 60 women with suspected genital tuberculosis, attending
      outpatient department of a tertiary care hospital. The aim was to evaluate the
      role and accuracy of laparoscopy in the diagnosis of genital tuberculosis. The
      patients were investigated for tuberculosis with Erythrocyte Sedimentation Rate,
      Montoux, chest X-ray, serum ELISA, CA125, ultrasonography, endometrial biopsy and
      laparoscopic biopsy. Culture or histopathology was taken as a gold standard for
      confirming the cases of genital tuberculosis. 30 patients were confirmed as
      positive. Comparison was made between the various diagnostic modalities. Baseline
      investigations like complete blood count, differential leukocyte count, ESR,
      Montoux, and some special tests like CA125 and serum ELISA were helpful in
      supporting the diagnosis in only some patients. The sensitivity, specificity,
      positive and negative predictive value of endometrial biopsy in diagnosing GT was
      6.6%, 100%, 100% and 51.7% respectively. Laparoscopic gross visualization alone,
      staining, culture and histology were able to detect 86.6%, 33.3%, 50% and 63.3%
      of cases respectively. Many patients would have been missed if laparoscopy was
      not performed. It helps in macroscopic visualization of pelvic cavity and
      obtaining biopsies for ZN staining, culture and histopathology. This increases
      the pickup rate of positive cases and helps in confirmation of the diagnosis.

PMID- 29332645
TI  - Plasma levels of Rifampicin and Pyrazinamide with pre and post meal
      administration in tuberculosis patients.
AB  - CONTEXT: Various factors affect plasma concentrations of antitubercular drugs in
      different populations so dosing schedule should be adjusted after therapeutic
      drug monitoring. AIMS: To study variability in plasma concentrations of
      Rifampicin and Pyrazinamide with pre and post-meal administration of drugs in
      tuberculosis patients. METHODS AND MATERIAL: 52 patients of pulmonary
      tuberculosis, divided in to two groups, pre and post-meal through systemic
      randomization. After taking pre-dose sample, drugs were administered according to
      the group. Samples were withdrawn at 2, 4, 6, and 10h after drug administration.
      Analysis of samples was done using HPLC. RESULTS: Mean+/-1SD of Cmax of
      Rifampicin was 7.75+/-2.82MUg/ml, mean+/-1SD of AUC0-10 was 42.17+/-17.25MUgh/ml,
      adjusted Tmax was 4.25h. In pre-meal samples, the corresponding values were
      7.75+/-2.88MUg/ml, 42.83+/-18.47MUgh/ml, 3.76h and in post-meal samples 8.03+/
      2.30MUg/ml, 41.56+/-16.46MUgh/ml and 4.75h. Mean+/-1SD of Cmax levels of
      Pyrazinamide was 54.49+/-21.86MUg/ml, mean+/-1SD of AUC0-10 was 337.94+/
      124.28MUgh/ml and adjusted Tmax was 3.49h. In pre-meal samples the corresponding
      values were 52.00+/-19.13MUg/ml, 329.96+/-112.11MUgh/ml, 3.23h, and in post-meal
      samples 57.43+/-23.61MUg/ml, 345.58+/-136.99MUgh/ml, 3.54h. CONCLUSION: There is
      huge variability in the plasma levels of Rifampicin and Pyrazinamide in
      population of this sub-himalayan region.

PMID- 29332644
TI  - Role of serum adenosine deaminase in pulmonary tuberculosis.
AB  - BACKGROUND: Definitive laboratory diagnosis and confirmation of tuberculosis
      remains a major challenge because of lack of specificity and sensitivity of
      diagnostic methods especially in sputum smear negative tuberculosis. Many studies
      have proved the role of ADA in diagnosis of tuberculosis in effusion fluids and a
      decrease in ADA activity after treatment. This study was aimed to investigate the
      role of serum ADA level as an early diagnostic and prognostic marker for
      pulmonary tuberculosis (PTB). MATERIAL AND METHODS: This was a cohort study done
      on patients visiting the OPD Clinics of the department of Pulmonary Medicine at
      GMCH, Chandigarh. 50 sputum positive and 50 sputum negative tuberculosis patients
      and 100 controls were recruited. Serum ADA levels were measured at the start of
      treatment and again after two months of treatment. Its correlation with severity
      of disease was seen. RESULTS: Mean serum ADA (IU/L) was found to be 35.293+/
      30.941 in PTB patients and 11.819+/-8.023 in control groups and the difference
      was found to be highly significant (P<0.00). Mean ADA was 31.107+/-29.32 in
      sputum positive patients, 39.478+/-32.22 in sputum negative and 11.819+/-8.0235
      in control groups. No statistically significant difference was observed amongst
      sputum positive and sputum negative patients. The levels decreased significantly
      after intensive phase of treatment. At the cut off values of 14.6IU/L, serum ADA
      had 78% sensitivity and 76% specificity (AUC=0.801, P value<0.00) to
      differentiate between PTB from healthy controls. CONCLUSION: Serum ADA levels may
      be used as a biomarker for diagnosis of PTB and to evaluate the response to
      treatment at follow up.

PMID- 29332646
TI  - Strategy and way forward for TB elimination.
AB  - India's National Strategic Plan (NSP) for TB Elimination 2017-25 looks ambitious
      in terms of targets of TB notification aiming to reach 35 lakh TB patients
      annually, i.e. double that of current status. Strategies and interventions
      designed under the Plan with patient centered approaches, with synergistic public
      private-patient partnership can make it possible to achieve real aim of reaching
      the unreached, by extending patient support systems and social protection to
      affected communities. In this review point, these strategies and commitments are
      summarized as future plan.

PMID- 29332647
TI  - Social support a key factor for adherence to multidrug-resistant tuberculosis
      treatment.
AB  - BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) is emerging as a major
      public health problem globally. Treatment success rates in MDR-TB across the
      globe are not encouraging as completing MDR-TB treatment successfully is
      challenging due to high proportion of lost to follow up. METHODS: Using
      qualitative methods and grounded theory approach, in-depth interviews were
      conducted with MDR-TB patients and treatment providers. The social cognitive
      framework was explored as a way to guide understanding of the factors affecting
      treatment adherence among MDR-TB patients. RESULTS: Multiple factors influenced
      patient's decision to adhere to MDR-TB treatment. Self-motivation, awareness
      about disease and treatment, counselling support, family support, nutritional
      support and social support were important drivers for successful treatment.
      Providers related that motivational counselling, nutritional support, family
      support and social support encouraged treatment adherence. CONCLUSION: To improve
      MDR-TB treatment adherence, a patient-centric approach should be considered at
      the programmatic level. There is a need to formulate strategy that includes
      motivational counselling, nutritional supplementation and social support
      mobilisation for treatment adherence. Participants suggested a Patient Support
      Group led treatment care model for better adherence and treatment success rates
      in MDR-TB treatment.

PMID- 29332648
TI  - Prevalence of chronic respiratory diseases from a rural area in Kerala, southern
      India.
AB  - BACKGROUND: Chronic lung diseases are one of the leading causes of morbidity in
      developing countries. A community based survey was undertaken with an objective
      to estimate the prevalence of chronic respiratory diseases and to describe the
      profile of people with CRDs in the rural area Nilamel health block in Kollam
      district, Kerala, southern India. METHODS: A household information sheet and a
      translated respiratory symptom questionnaire based on International Union against
      Tuberculosis and Lung Disease (IUATLD) bronchial symptoms questionnaire was
      administered to 12,556 people above 15 years, selected randomly from Nilamel
      health block. RESULTS: Prevalence of self reported asthma was 2.82% (95% CI 2.52
      3.12) and that of chronic bronchitis was 6.19% (95% CI 5.76-6.62) while other
      CRDs which did not fit to either constitute 1.89%. Prevalence of asthma among
      males was 2.44% (95% CI 2.05-2.85) while that of females was 3.14% (95% CI 2.71
      3.57). Chronic bronchitis prevalence was 6.73% and 5.67% among males and females
      respectively. CONCLUSION: Although India has devised a programme to combat
      cancer, diabetes, cardio vascular disease and stroke, none have been devised for
      chronic respiratory illness till date. Considering high prevalence and its
      contributions to morbidity and mortality, a comprehensive programme to tackle
      chronic respiratory diseases is needed.

PMID- 29332649
TI  - Isoniazid and rifampicin heteroresistant Mycobacterium tuberculosis isolated from
      tuberculous meningitis patients in India.
AB  - BACKGROUND: Heteroresistant Mycobacterium tuberculosis (mixture of susceptible
      and resistant subpopulations) is thought to be a preliminary stage to full
      resistance and timely detection, initiation of correct treatment is vital for
      successful anti tubercular therapy. The aim of this study was to detect multi
      drug resistant (MDR) and heteroresistant M. tuberculosis with the associated gene
      mutations from patients of tuberculous meningitis. METHODS: A total of 197 M.
      tuberculosis isolates from 478 patients of TBM were isolated from July 2012 to
      July 2015 and subjected to drug susceptibility testing (DST) by BACTEC MGIT and
      Genotype MTBDR line probe assay (LPA). Heteroresistance was defined as presence
      of both WT and mutant genes in LPA. RESULTS: Of 197 M. tuberculosis isolates, 11
      (5.6%) were MDR, 23 (11.6%), 1 (0.5%) were mono resistant to isoniazid (INH) and
      rifampicin (RMP) respectively. Heteroresistance was detected in 8 (4%), 2 (1%)
      isolates to INH and RMP respectively. INH heteroresistant strains had WT bands
      with mutation band S315T1 whereas RMP heteroresistant strains had WT bands with
      mutation band S531L. CONCLUSION: The prevalence of MDR M. tuberculosis was 5.6%
      in TBM patients with the most common mutation being DeltaWT band with S315T1 for
      INH and DeltaWT band with S531T for RMP. MGIT DST was found to be more sensitive
      for detecting overall resistance in M. tuberculosis but inclusion of LPA not only
      reduced time for early initiation of appropriate treatment but also enabled
      detection of heteroresistance in 8 (4%), 2 (1%) isolates for INH and RMP
      respectively.

PMID- 29332650
TI  - Amplification of Hsp 65 gene and usage of restriction endonuclease for
      identification of non tuberculous rapid grower mycobacterium.
AB  - BACKGROUND: The rapid grower mycobacteria have emerged as significant group of
      human pathogen amongst the Runyon group IV organisms that are capable of causing
      infection in both the healthy and immunocompromised hosts. Study aimed to
      identification of species amongst rapid grower non tuberculous mycobacterial
      isolates by polymerase chain reaction - restriction enzyme analysis (PRA).
      Analysis and comparison of results with standard biochemical tests. METHODS:
      Rapid grower non tuberculous mycobacteria had been collected from liquid culture
      section during the study period. All isolates were identified by conventional
      biochemical tests. A 441bp fragment of hsp65 genes was amplified and digested by
      two restriction enzymes, BstEII and HaeIII. Digested products were analyzed using
      polyacrilamid gel electrophoresis (PAGE). RESULTS: During study, 121 rapid grower
      mycobacterial isolates were subjected for species identification. Isolates were
      obtained from pulmonary samples (72) and extrapulmonary samples (49). In the PRA
      test 8 different types of rapid grower mycobacteria were identified after
      analyzing the fragments generated through restriction enzymes. Mycobacterium
      chelonae (57/121) was the most common isolate in pulmonary and extrapulmonary
      samples. Mycobacterium fortuitum (42), Mycobacterium abscessus (11),
      Mycobacterium immunogen (06), Mycobacterium peregrinum (02), Mycobacterium
      smegmatis (01), Mycobacterium wolinskyi (01), Mycobacterium goodii (01) were
      identified as other species of rapid grower non tuberculous mycobacteria.
      CONCLUSION: PRA is a rapid and accurate system for the identification of species
      of non tuberculous mycobacteria. Results of PRA and biochemical tests are
      concordant up to 98%.

PMID- 29332651
TI  - Koch's postulates - Pitfalls and relevance in the 21st century.

PMID- 29332652
TI  - Initial airflow obstruction in new cases of pulmonary tuberculosis: Complication,
      comorbidity or missed?
AB  - : Tuberculosis (TB) may have a similar spirometry findings as a chronic
      obstructive pulmonary disease but the prevalence of TB-induced airflow
      obstruction (AO) is still unknown. OBJECTIVES: To measure frequency of AO in new
      TB cases at the beginning of treatment and to evaluate factors associated with
      obstructive abnormalities following TB diagnosis. MATERIALS AND METHODS: 317
      patients that have no history of prior AO were recruited into the study with a
      median age of 39.0 years (IQR, 30.0-49.0). AO was defined using the
      FEV1/F(VC)<LLN. RESULTS: AO was detected in 29.97% (95/317) new TB cases. These
      patients had a more severe clinical manifestation of TB with a greater likelihood
      of cough, OR=5.47 (95%CI 1.90-15.70) and wheezing, OR=10.51 (95%CI 5.72-19.27),
      p<0.001. The frequency of AO was positively associated with bronchoscopic
      evidence of narrowing of the main airways. Furthermore, from multiple logistic
      regression analysis we would assume that higher FEV1 value in TB patients with AO
      was related to greater BMI and inversely associated with older age, female sex
      and radiographic extent (p<0.05). CONCLUSIONS: Obstructive pattern on spirometry
      frequently occurs in new TB cases without previously detected AO. This category
      of patients should be targeted for detailed follow-up, particularly, in high TB
      burden countries.

PMID- 29332653
TI  - Efficacy of alternate day Directly Observed Treatment Short-course (DOTS) in
      skeletal tuberculosis - A retrospective study.
AB  - OBJECTIVE: To assess the efficacy of alternate day (thrice a week) Directly
      Observed Treatment Short-course (DOTS) regimen spanning six to nine months in
      providing sustained cure for skeletal tuberculosis (TB) under programmatic
      conditions. DESIGN: Retrospective cohort study. SETTING: An urban district
      tuberculosis centre in India under the Revised National Tuberculosis Programme.
      PARTICIPANTS: A cohort of 218 patients treated with alternate day DOTS regimen
      for skeletal TB between 2007 and 2012. METHODS: All patients with the diagnosis
      of skeletal TB registered between 2007 and 2012 who successfully completed
      treatment were followed up for evidence of disease recurrence or relapse using
      structured interviews conducted between August 2013 and October 2015 after
      ensuring a minimum follow up of two years. RESULTS: Of the 200 patients eligible
      for follow up in this study, 117 (58.5%) had a minimum follow up of two years.
      The remaining 83 cases could not be traced. 105 (89.7%) of these 117 patients
      were symptom free for two years or more after the completion of treatment. There
      were four cases who had a relapse of the disease within two years of completion
      of treatment. Eight cases were administered further ATT soon after the completion
      of treatment under DOTS. CONCLUSIONS: This study confirms the efficacy of the
      alternate day DOTS regimen in successfully treating all forms of skeletal TB,
      including spinal TB, with a success rate of 89.7%.

PMID- 29332654
TI  - Evaluation of loop mediated isothermal amplification (LAMP) assay in the
      diagnosis of tubercular lymphadenitis: A pilot study.
AB  - Tubercular lymphadenitis (TBLA) contributes to 30-40% of extrapulmonary TB cases
      in the immunocompetent individuals and 40-50% in people with HIV. Current
      diagnostic methods for TBLA like Gene-Xpert or PCR are costly and conventional
      methods like fine needle aspiration cytology, histopathology lack sensitivity and
      specificity. Culture which is considered as gold standard require high turnaround
      time. Loop mediated isothermal amplification (LAMP) assay has been developed as a
      novel technique for nucleic acid amplification and has shown promising results in
      the diagnosis of pulmonary tuberculosis. Present study evaluated the Nu-LAMPTM TB
      Kit (RAS Life Sciences Pvt. Ltd, a bioMerieux group company) for diagnosis of
      TBLA comparing with conventional tests (cytology, ZN smear, culture). The
      sensitivity, specificity, PPV and NPV of LAMP assay was found to be 33.3%, 91.2%,
      40% and 88.57% as compared to 100%, 76.5%, 42.9% and 100% of ZN staining and
      100%, 73.5%, 40% and 100% of cytopathology. The low sensitivity of LAMP assay in
      the present study addresses the need for comparison and validation of the
      commercially available LAMP kits before used for patient diagnosis.

PMID- 29332655
TI  - Research on tuberculosis in tribal areas in India: A systematic review.
AB  - BACKGROUND: Tuberculosis (TB) remains a major public health problem in resource
      poor countries including India. Scientific knowledge is used to guide policy and
      practice. There is however, a limited, systematically collected data required for
      guiding the scale-up of interventions particularly amongst vulnerable populations
      including tribal groups in the country. In view of this, a systematic review of
      the TB research studies carried out in tribal areas of different parts of the
      country was undertaken. OBJECTIVE: To undertake a systematic review of the TB
      research studies carried out in tribal areas of India between 1996 and 2016.
      METHODS: A systematic review of English articles published between 1996 and 2016
      on any aspect of TB was done through internet searches using Literature search
      EndNote programme. The words used for searching were tuberculosis, India, tribal,
      indigenous, disadvantaged, adivasi. The most common topics classified as annual
      risk of tuberculosis infection (ARTI), prevalence of TB, laboratory studies,
      clinical symptoms of TB, risk factors for TB, knowledge attitude practice,
      community Directly Observed Treatment (DOT) providers, performance of Revised
      National Tuberculosis Control Programme (RNTCP), and drug resistant TB.
      Classification was also done on the basis of the type of tribe studied and place
      of study conducted. A total of 47 studies identified through the search were
      included in the review. RESULTS: Of the 47 studies reviewed, 12 were on TB
      prevalence, 7 were laboratory studies, four on ARTI and 5 on performance of RNTCP
      in tribal areas. Among these, majority (23 studies) of the tribal studies did not
      mention the type of tribe. Ten studies were conducted among Saharia, a
      particularly vulnerable tribal group in the Indian state of Madhya Pradesh mainly
      by the National Institute for Research on Tribal Health, five were among the
      mixed tribes and very few on other tribes. CONCLUSION: The systematic review
      indicates that the research studies on TB among tribal population are very few.
      There is a need to invest and encourage researcher to work on the research plans
      for the control of TB in tribal areas.

PMID- 29332656
TI  - Germ cell tumor causing pleural effusion: A diagnostic dilemma.
AB  - Straw colored pleural fluid with raised adenosine deaminase (ADA) levels in young
      healthy adults usually raises suspicion of tuberculosis, sometimes leading to
      laxity in carrying thorough physical examination and missing out some important
      clues with potential disastrous consequences. A 35-year-old male was diagnosed to
      have left pleural effusion and anti-tubercular treatment was started on the basis
      of straw colored, lymphocyte-predominant pleural fluid with significantly raised
      ADA levels. When there was no improvement after 1 month of treatment he was
      investigated further and found to have a mediastinal mass along with hydro
      pneumothorax. Fine needle aspiration cytology (FNAC) of the mass was done twice
      at different centers with different reports followed by biopsy from the mass to
      settle the diagnosis. Histopathological examination revealed yolk sac tumor.
      Testicular ultrasound showed a mass with ill-defined hypoechoic areas and
      lobulated margins in left testis, which was missed on clinical examination. Serum
      lactate dehydrogenase (LDH) and alpha fetoprotein (AFP) levels were found to be
      elevated. Beta-human chorionic gonadotropin (beta-hCG) was normal. The final
      diagnosis of nonseminomatous germ cell tumor with mediastinal metastasis was
      made. The present case underlines the importance of good clinical examination, an
      art which is diminishing with availability of sophisticated investigations and a
      thin line of difference between potentially curable and fatal diagnosis,
      especially in young population, where malignancy is overlooked as a differential
      diagnosis. Furthermore, despite all its advantages, too much reliance on FNAC may
      be responsible for misdiagnosis in certain cases.

PMID- 29332657
TI  - Primary oral tuberculosis on the tongue mimicking squamous cell carcinoma.
AB  - Tuberculosis is chronic granulomatous disease with rare oral manifestations. But
      if so are overlooked by most of the health care professionals. Clinically, most
      of the times, a tuberculous ulcer may mimic an ulcer of malignant origin and may
      be misdiagnosed. So, keeping in mind the etiology and the nature of the ulcer, it
      should be differentially diagnosed and a histopathological examination should
      only confirm the final diagnosis of the ulcer.

PMID- 29332658
TI  - An extremely rare association of Sweet's syndrome with active pulmonary
      tuberculosis.
AB  - Sweet's syndrome is a skin manifestation of various systemic infections, drugs,
      malignancies and autoimmune disorders. There are very few case reports describing
      the relationship between Sweet's syndrome and non-tubercular mycobacterium
      infection. Further development of Sweet's syndrome secondary to mycobacterium
      tuberculosis (active pulmonary tuberculosis) is extremely uncommon and this is
      the second well established case reported from India. Here we report a forty
      eight year old man who presented with multiple erythematous and tender plaques
      over neck, palms and sides of soles. He also had high grade fever, headache,
      myalgias, cough, chest pain and difficulty in breathing. With clinical
      possibilities of (1) Sweet's syndrome with pulmonary involvement and (2) Sweet's
      syndrome secondary to pulmonary infection, we send the skin biopsy for
      histopathological examination and also advised routine laboratory plus imaging
      investigations to find out the underlying cause. Clinical and lab parameters
      together with the biopsy report fulfilled the diagnostic criteria for Sweet's
      syndrome. Further chest X-ray findings, demonstration of acid fast bacilli of
      mycobacterium tuberculosis on sputum smear microscopy and MGIT report confirmed
      the diagnosis of pulmonary tuberculosis. Patient was put on colchicine and
      standard anti-tubercular drugs. Significant improvement was noticed in skin
      lesions within five days of treatment and no recurrence has been seen for the
      past six months.

PMID- 29332659
TI  - A case of hepatic tuberculosis: A tuberculoma.
AB  - Tuberculosis (TB) is a common cause of morbidity and mortality worldwide and its
      eradication in the United States has stalled for the first time in decades.
      Isolated hepatic TB is an extremely uncommon form of extrapulmonary TB. Here we
      present a case of a tuberculous liver abscess and suggest that TB should be
      considered in patients who fail to respond to antibiotics and prompt diagnostic
      intervention.

PMID- 29332660
TI  - IS6110 PCR for the early diagnosis of paediatric tuberculosis in India.

PMID- 29332661
TI  - Soft tissue tuberculosis - An unusual presentation of a common disease.
AB  - Tuberculosis (TB) has reached epidemic proportions in India with a myriad of
      clinical presentations. Extra pulmonary TB can present in a wide variety of
      clinical forms and its identification requires a high degree of clinical
      suspicion. Soft tissue infection by Mycobacteria is rare. The diagnosis is often
      not thought of owing to the rarity of this entity.

PMID- 29332662
TI  - A survivorship study of 838 total elbow replacements: a report from the Norwegian
      Arthroplasty Register 1994-2016.
AB  - BACKGROUND: The aim of this study was to present the long-term survivorship (20
      years) of total elbow arthroplasty (TEA) for a relatively large population and to
      compare different prosthesis brands and patient subgroups. METHODS: Between 1994
      and 2017, a total of 838 primary TEAs were reported to the Norwegian Arthroplasty
      Register. Implant survival was calculated using the Kaplan-Meier method. Risk
      differences were examined using Cox regression analyses and exact Cox regression
      for rare events. We compared the survivorship of the 8 most frequently used
      implant brands, the different diagnoses leading to TEA, and the influence of the
      fixation technique. RESULTS: The overall 5-, 10-, 15-, and 20-year survival rates
      for all elbow arthroplasties were 92%, 81%, 71%, and 61%, respectively. Risk
      factors for revision were a diagnosis of sequelae after trauma and cementless
      fixation of the ulna component. There were some differences between the implant
      brands. The Norway prostheses had higher survival compared with the Kudo after 15
      years of follow-up (78% and 66%, respectively; P < .001). Among the implants with
      shorter follow-up, the IBP and NES had inferior survivorship compared with the
      Norway. The frequently used Discovery had promising survivorship up to 5 years.
      The most frequent reason for revision surgery was aseptic loosening, followed by
      defective polyethylene, infection, and dislocation. The revision causes were to
      some degree implant specific. CONCLUSION: Fairly good results in terms of
      prosthesis survival were obtained with TEA, although results were poorer than for
      knee and hip arthroplasties.

PMID- 29332663
TI  - Results after radial head arthroplasty in unstable fractures.
AB  - BACKGROUND: Whereas most radial head fractures are stable injuries, they
      sometimes occur as part of complex injury patterns with associated elbow
      instability. Radial head arthroplasty has been favored in patients with
      unreconstructable radial head fractures and unstable elbow injuries. The purpose
      of this study was to review radiographic outcomes, functional outcomes, and
      complications after radial head arthroplasty for radial head fracture in unstable
      elbow injuries. METHODS: This study was a retrospective review of radial head
      fractures treated with radial head arthroplasty by a single surgeon during a 15
      year period. Demographics of the patients, injury details, operative reports,
      radiographic and clinical outcomes, and any complications were recorded. Patients
      were divided into stable and unstable elbow injury groups. RESULTS: A total of 68
      patients were included. There were 50 unstable fractures that were compared with
      18 stable fractures. Patients with unstable radial head fractures with associated
      elbow dislocation achieved mean flexion and mean forearm rotational arc of motion
      similar to that of patients with stable radial head fractures. However,
      supination loss was greater in the unstable group than in the stable fracture
      group, with a mean difference of 10 degrees . Radiographic outcomes and
      complication rates did not differ between injury groups. There was no observed
      decrease in implant longevity in patients with unstable elbow injuries.
      CONCLUSIONS: Radial head arthroplasty is an effective option for treatment of
      unstable elbow injuries, with recovery of functional elbow range of motion and no
      difference in complication rate or implant survivorship compared with those
      patients with stable injuries.

PMID- 29332664
TI  - Rounded data have a high potential for false comparative statistical results as
      shown with elbow arc of motion.
AB  - BACKGROUND AND HYPOTHESIS: Visually measured range-of-motion (ROM) data are
      usually rounded to the nearest 5 degrees  interval and then recorded. Rounding
      might significantly influence the outcome of statistical tests. METHODS: We
      performed numerical simulation of t test application on 2 datasets, as typically
      reported for the elbow flexion-extension arc of motion. The test was performed on
      exact data and then repeated on the same data rounded to the nearest 5 degrees 
      interval. The simulation input parameters were as follows: difference in means (1
      degrees -30 degrees ), standard deviation (1 degrees -30 degrees ), and number of
      cases (15, 30, 60, and 120). Diverging results were counted to find the rate of
      failure. RESULTS: Depending on the given difference in means, the given standard
      deviation, and the number of cases, the failure rate of the t test after rounding
      reached up to 40%. DISCUSSION AND CONCLUSION: The accuracy of statistical tests
      performed on rounded ROM data is limited because of loss of information after
      rounding to the nearest 5 degrees  interval. This affects parametric and
      nonparametric tests, as well as paired and unpaired tests. In the future, authors
      should specify how ROM has been measured and recorded, explicitly addressing
      rounding. Furthermore, to test a zero hypothesis on rounded ROM data, authors
      should apply our P value (alpha) correction.

PMID- 29332665
TI  - Performance outcomes after medial ulnar collateral ligament reconstruction in
      Major League Baseball positional players.
AB  - BACKGROUND: We sought to determine whether professional baseball positional
      players who underwent medial ulnar collateral ligament (MUCL) reconstruction
      demonstrate decreases in performance on return to competition compared with
      preoperative performance metrics and their control-matched peers. METHODS: Data
      for 35 Major League Baseball positional players who underwent MUCL reconstruction
      during 31 seasons were obtained. Twenty-six players met inclusion criteria.
      Individual statistics for the 2 seasons immediately before injury and the 2
      seasons after injury included wins above replacement (WAR), on-base plus slugging
      (OPS), and isolated power (ISO). Twenty-six controls matched by player position,
      age, plate appearances, and performance statistics were identified. RESULTS: Of
      the 35 athletes who underwent surgery, 7 did not return to their preinjury level
      of competition (return to play rate of 80%). In comparing preinjury with
      postinjury statistics, players exhibited a significant decrease in plate
      appearances, at-bats, and WAR 2 seasons after injury but did not demonstrate
      declines in WAR 1 season after injury. Compared with matched controls, athletes
      who underwent MUCL reconstruction did not demonstrate significant decline in
      statistical performance, including OPS, WAR, and ISO, after return to play from
      surgery. Of all positional players, catchers undergoing surgery demonstrated
      lowest rates of return to play (56%) along with statistically significant
      decreases in home run rate, runs batted in, and ISO. CONCLUSION: Major League
      Baseball positional players undergoing MUCL reconstruction can reasonably expect
      to return to their preinjury level of competition and performance after surgery
      compared with their peers. Positional players return to play at a rate comparable
      to that of pitchers; catchers may experience more difficultly in returning to
      preinjury levels of play.

PMID- 29332667
TI  - Letter to the Editor regarding Tokish et al: "Pseudoparalysis: a systematic
      review of term definitions, treatment approaches, and outcomes of management
      techniques".

PMID- 29332666
TI  - Optimizing reverse shoulder arthroplasty component position in the setting of
      advanced arthritis with posterior glenoid erosion: a computer-enhanced range of
      motion analysis.
AB  - BACKGROUND: Our study purpose was to determine the optimal glenoid and humeral
      reverse shoulder arthroplasty (RSA) component design and position in
      osteoarthritic shoulders with severe glenoid retroversion deformities. METHODS:
      Computed tomography scans from 10 subjects were analyzed with advanced software
      including RSA range of motion (ROM) analysis. Variables included glenoid
      component retroversion of 0 degrees , 5 degrees , 10 degrees , 15 degrees , and
      20 degrees  and baseplate lateralization of 0, 5, and 10 mm. Humeral variables
      included 135 degrees , 145 degrees , and 155 degrees  angle of inclination (AOI)
      combined with variable humeral offset. RESULTS: Glenoid component lateralization
      had the greatest influence on ROM. In comparing each ROM direction among all
      lateralization options independently, there were significantly greater adduction,
      abduction, external rotation, extension, and flexion motions with progressively
      greater lateralization. Internal rotation motion was greater at 10 mm only. In
      analyzing the effects of glenoid version independently, no differences in
      adduction or abduction ROM were seen. With greater retroversion, decreased
      external rotation and extension motion was noted; however, greater internal
      rotation and flexion motion was seen with the exception of flexion at 10 mm of
      lateralization. For adduction, external rotation, and extension, a more valgus
      AOI resulted in less ROM at each progressively greater AOI independent of humeral
      lateralization. Internal rotation and flexion motions were greater with a more
      varus AOI but not significant between each inclination angle. Abduction ROM was
      maximized with a more valgus AOI. Humeral lateralization had no effect on ROM.
      CONCLUSIONS: In the setting of RSA for advanced glenoid osteoarthritic
      deformities, optimal ROM is achieved with 10-mm baseplate lateralization and
      neutral to 5 degrees  of retroversion mated to a humeral implant with a varus
      (135 degrees ) inclination angle.

PMID- 29332668
TI  - Response to Burkhart regarding: "Pseudoparalysis: a systematic review of term
      definitions, treatment approaches, and outcomes of management techniques".

PMID- 29332669
TI  - A fleeting rest from the battle.

PMID- 29332670
TI  - Reliability and construct validity of the Children's Sleep Habits Questionnaire
      in Chinese kindergartners.
AB  - The Children's Sleep Habits Questionnaire (CSHQ) is widely used in clinical
      settings to screen for sleep problems in children aged 4-10 years. Existing
      studies on children in different cultures have included children across a wide
      age range and results have raised questions about CSHQ's psychometric quality.
      Our study addressed some of the limitations of existing studies by focusing on
      Chinese children within a much narrower age range of 4-5 years old. We tested the
      reliability and construct validity of the CSHQ in children living in Shanghai,
      China. Parents (mothers: 93%) of a random selected sample of kindergarten
      children aged 4-5 years (N=171; 46.8% boys; one target child per family) from
      Shanghai, China provided data on their children's sleep behaviors. CFA and EFA
      were conducted using Mplus 7.3. Weighted least squares with mean and variance
      adjusted (WLSMV) were used as the estimation method in Mplus, due to the ordinal
      nature of item responses. Our analyses showed that, similar to most existing
      studies, the eight subscales of CSHQ had low internal consistency, with
      Cronbach's alphas ranged from .11 (Night Waking) to .62 (Daytime Sleepiness). CFA
      failed to confirm the 8-factor structure. EFA suggested that a six-factor
      structure should be extracted. Subsequent CFA with a newly identified set of
      items from CSHQ led to the exclusion of two uninterpretable factors, leaving four
      factors with 28 items: Bedtime Behaviors (alpha=.59), Sleep Behaviors
      (alpha=.62), Morning Wakings (alpha=.69), and Daytime Sleepiness (alpha=.67). The
      four factors represented some improvement to the psychometric quality of the
      CSHQ. Based on our findings and those from other studies, we concluded that the
      CSHQ should be used with great caution.

PMID- 29332671
TI  - Estimating sleep efficiency in 10- to- 13-year-olds using a waist-worn
      accelerometer.
AB  - OBJECTIVE: In field settings, wrist- and waist-worn accelerometers are typically
      used to assess sleep characteristics and movement behaviors, respectively. There
      has been a shift in movement behavior studies to wear accelerometers 24 h/d.
      Sleep characteristics could be assessed in these studies if sleep algorithms were
      available for waist-worn accelerometers. The objective of this study was to
      develop and provide validity data for an algorithm/sleep likelihood score cut-off
      to estimate sleep efficiency in children using the waist-worn Actical
      accelerometer. DESIGN: Cross-sectional study. PARTICIPANTS: Fifty healthy
      children aged 10-13 years. MEASUREMENTS: Children wore an Actical on their waist
      and an Actiwatch 2 on their nondominant wrist for 8 nights at home in their
      normal sleep environment. Participants were randomized into algorithm/sleep
      likelihood score "development" and "test" groups (n=25 per group). Within the
      development group, we assessed sleep efficiency with the Actical using the same
      algorithm that the Actiwatch 2 uses and selected the sleep likelihood score cut
      off value that was the most accurate at predicting sleep efficiency at the
      nightly level compared with the Actiwatch 2. We applied this algorithm and cut
      off value to the test group. RESULTS: Mean (SD) sleep efficiency estimates for
      the test group from the Actical and Actiwatch 2 were 89.0% (3.9%) and 88.7%
      (3.1%), respectively. Bland-Altman plots and absolute difference scores revealed
      considerable agreement between devices for both nightly and weekly estimates of
      sleep efficiency. CONCLUSION: A waist-worn Actical accelerometer can accurately
      predict sleep efficiency in field settings among healthy 10- to 13-year-olds.

PMID- 29332672
TI  - Motivational factors associated with drowsy driving behavior: a qualitative
      investigation of college students.
AB  - OBJECTIVES: This qualitative investigation sought to identify the motivational
      factors that contribute to drowsy driving in college students and to discover
      important messaging strategies that may help prevent or reduce this behavior in
      this population. DESIGN: Four focus groups of college students. SETTING: A large
      university in the Washington, DC, metropolitan area during the Fall 2016 term.
      PARTICIPANTS: Twenty-six undergraduate students between the ages of 18 and 25
      years. MEASUREMENTS: Notes and transcripts from the focus group sessions were
      analyzed to identify recurring themes regarding attitudes, motivations,
      experiences, influences, and potential preventive messaging strategies related to
      drowsy driving. RESULTS: Although most participants had heard of drowsy driving
      and were concerned about it, they did not associate it with legal risks and were
      more concerned about alcohol-impaired and distracted driving as crash risks.
      Participants viewed drowsy driving as a normal and unavoidable part of their
      lives over which they had little control. For potential anti-drowsy driving
      messaging strategies, participants preferred messages delivered via audiovisual
      or social media that featured graphic and emotional portrayals of crashes and
      their consequences. Participants also voiced strong support for preventive
      messaging strategies equating various degrees of sleep deprivation to known
      impairing levels of alcohol, as well as messages providing cues to action to
      actual drowsy drivers on roadways. CONCLUSIONS: Increased enforcement, education,
      and public messaging campaigns are needed to increase knowledge and influence
      attitudes and opinions among young drivers about the dangers and social
      unacceptability of drowsy driving.

PMID- 29332673
TI  - Prevalence and comorbidity of sleep conditions in Australian adults: 2016 Sleep
      Health Foundation national survey.
AB  - OBJECTIVE: To determine the prevalence of sleep conditions (obstructive sleep
      apnea [OSA], insomnia symptoms, simple snoring, and restless legs) and their
      associated burden of chronic conditions in a community sample. DESIGN: Cross
      sectional national adult online survey. SETTING: Community-based sample.
      PARTICIPANTS: Australian adults >=18 years, N = 1011. MEASUREMENTS: A cross
      sectional national online survey assessed diagnosed OSA, OSA symptoms, insomnia
      symptoms, sleep problems, excessive daytime sleepiness (Epworth Sleepiness Scale
      >=11), and physician-diagnosed health conditions (heart disease, diabetes,
      hypertension, reflux disease, lung disease, depression, anxiety/panic disorder,
      arthritis). Possible undiagnosed OSA was estimated using self-reported frequent
      loud snoring and witness apneas. International Criteria for Sleep Disorders-3
      criteria identified insomnia symptoms. Logistic regression models adjusted for
      age, sex, obesity, and smoking determined correlates of sleep disorders. RESULTS:
      Comorbid sleep conditions were common, with 56% of participants demonstrating >=1
      condition. Reporting >=1 mental health condition (depression and/or anxiety) was
      independently associated with diagnosed OSA (odds ratio [95% confidence interval
      {CI}]: 6.6 [3.2-13.6]), undiagnosed OSA (3.2 [1.8-5.8]), simple snoring (2.4 [1.2
      4.5]), insomnia symptoms (4.3 [2.5-7.3]), and restless legs (1.9 [1.2-3.1]).
      Diagnosed OSA was significantly associated with >=1 cardiometabolic condition
      (2.9 [1.4-6.0]) and arthritis (3.6 [1.8-7.2]). ESS >=11 was associated with
      diagnosed (3.1 [1.4-6.8]) and undiagnosed OSA (6.2 [3.4-11.4]), insomnia symptoms
      (2.6 [1.4-4.9]), and restless legs (2.3 [1.4-4.0]), and these sleep conditions
      were also significantly associated with >=2 diagnosed medical problems.
      CONCLUSION: Strategies to facilitate the diagnosis and management of often
      comorbid sleep disorders in primary care are required to reduce the significant
      sleep-related disparities in cardiometabolic and mental health.

PMID- 29332674
TI  - Sleep apnea and pesticide exposure in a study of US farmers.
AB  - INTRODUCTION: Carbamate and organophosphate pesticides inhibit
      acetylcholinesterase, and poisoning leads to respiratory depression. Thus,
      involvement in sleep apnea is plausible, but no data exist at lower levels of
      exposure. Other pesticides could impact sleep apnea by different mechanisms but
      have not been studied. Our study examines the associations between pesticide
      exposure and sleep apnea among pesticide applicators from a US farming
      population. PARTICIPANTS AND METHODS: We analyzed data from 1569 male pesticide
      applicators, mostly farmers, from an asthma case-control study nested within the
      prospective Agricultural Health Study. On questionnaires, participants reported
      use of specific pesticides and physician diagnosis plus prescribed treatments for
      sleep apnea. We used multivariable logistic regression to estimate associations
      between ever use of 63 pesticides and sleep apnea (234 cases, 1335 noncases).
      RESULTS: The most notable association was for carbofuran, a carbamate (100
      exposed cases, odds ratio 1.83, 95% confidence interval 1.34-2.51, P=.0002).
      Carbofuran use began before reported onset of sleep apnea in all cases.
      DISCUSSION: This study adds to the known adverse health outcomes of exposure to
      carbofuran, a pesticide canceled in the United States in 2009 for most
      agricultural purposes but persists in the environment and remains in use in some
      other countries. CONCLUSIONS: We conducted the first epidemiological study
      investigating the association of pesticide exposure and sleep apnea. Our results
      in a male agricultural population suggests that exposure to carbofuran is
      positively associated with sleep apnea.

PMID- 29332675
TI  - Sleep duration and incidence of type 2 diabetes: the Multiethnic Cohort.
AB  - OBJECTIVES: As an emerging risk factor for the rising incidence of type 2
      diabetes, we examined sleep duration in relation to type 2 diabetes and several
      biomarkers. DESIGN: Prospective cohort recruited 1993-1996. SETTING: The
      Multiethnic Cohort in Hawaii and California. PARTICIPANTS: A cohort of 151,691
      White, African American, Japanese American, Native Hawaiian, and Latino
      participants; 9695 cohort members had biomarker measurements. MEASUREMENTS: Sleep
      duration was self-reported at cohort entry. Diabetes status was obtained from 3
      questionnaires and confirmed by 3 administrative data sources. Biomarkers were
      measured by standard assays 9.6+/-2.1 years after cohort entry. We estimated
      diabetes risk as a time-varying outcome using Cox regression adjusted for body
      mass index assessed at 3 time points and other known confounders and computed
      adjusted means of biomarkers by sleep hours. RESULTS: During 7.9+/-3.5 years of
      follow-up, 8487 new diabetes cases were diagnosed. Long sleep duration (>=9
      hours), as compared with 7-8 hours, was significantly associated with higher
      incidence (hazard ratio, 1.12; 95% confidence interval 1.04-1.21), but the 4%
      elevated incidence for short sleep duration (<=6 hours) did not reach
      significance (95% confidence interval 0.99-1.09). After stratification, the
      associations appeared stronger in Japanese American than other ethnic groups and
      in participants without comorbidity. Hours of sleep were positively associated
      with C-reactive protein and triglycerides and inversely related to high-density
      lipoprotein cholesterol and adiponectin but not with leptin levels and
      homeostatic model assessment of insulin resistance. CONCLUSION: In this
      multiethnic population, the 12% higher diabetes risk for long sleep hours may be
      mediated through inflammation, a poor lipid profile, and lower adiponectin
      levels.

PMID- 29332677
TI  - Pilot study of sleep and meal timing effects, independent of sleep duration and
      food intake, on insulin sensitivity in healthy individuals.
AB  - This pilot study tested the independent and interactive effects of sleep and meal
      times, under identical sleep duration and feeding conditions, on insulin
      sensitivity (Si) in overweight adults. Participants underwent a 4-phase
      randomized crossover inpatient study differing in sleep times: normal (Ns: 0000
      0800 hours) or late (Ls: 0330-1130 hours); and in meal times: normal (Nm: 1, 5,
      11, and 12.5 hours after awakening) or late (Lm: 4.5, 8.5, 14.5, and 16 hours
      after awakening). An insulin-modified frequently sampled intravenous glucose
      tolerance test, at scheduled breakfast time, and a meal tolerance test, at
      scheduled lunch time, were performed to assess Si after 3 days in each condition.
      Six participants were enrolled (4 men, 2 women; mean age 25.1+/-[SD] 3.9 years,
      body mass index 29.2+/-2.7 kg/m2); only 1 failed to complete her last study
      phase. There were no effects of sleep and meal times or sleep * meal time
      interaction on Si (all P>.35), acute insulin response to intravenous glucose (all
      P>.20), and disposition index (all P>.60) after adjusting for sex and body mass
      index. Meal tolerance test glucose and insulin areas under the curve were lower
      during Nm (glucose P=.11; insulin P=.0088). There were a sleep * meal interaction
      and an effect of meal times on overnight glucose (P=.0040 and .012, respectively)
      and insulin (P=.0075 and .067, respectively). Sleep timing, without concomitant
      sleep restriction, does not adversely affect Si and glucose tolerance, but meal
      times may be relevant for health. Our results should be confirmed in a larger
      sample.

PMID- 29332678
TI  - Relationship of sleep pattern and snoring with chronic disease: findings from a
      nationwide population-based survey.
AB  - OBJECTIVES: To investigate the association of total sleep time and presence or
      absence of snoring with chronic disease among the Bangladeshi adult population.
      DESIGN: Cross-sectional survey. SETTING: Urban and rural Bangladesh.
      PARTICIPANTS: A total of 12,338 men and women aged >=35 years. MEASUREMENTS:
      Total sleep time was considered as the total hours of sleep in 24 hours.
      Furthermore, sleep time was categorized into <7, 7-9, and >9 hours according to
      National Sleep Foundation (2015) guidelines. Self-reported snoring history was
      captured and corroborated with their respective sleep partner/spouse in more than
      80% cases. Registered physician-diagnosed current and/or previous cases of
      hypertension, diabetes, coronary heart disease, cancer, stroke, chronic
      obstructive pulmonary disease, and any other chronic conditions were counted.
      RESULTS: Overall prevalence of at least 1 chronic disease in our study population
      was around 18%: men (15.4%) and women (20.0%). Hypertension has the highest
      prevalence (overall: 12.7%, men: 12.2%, women: 15%) followed by diabetes (4.9%),
      coronary heart diseases (3.2%), stroke (1.8%), chronic obstructive pulmonary
      disease (0.9%), and cancer (any type: 0.1%). Sleep pattern and snoring are
      significantly associated with all individual chronic disease except cancer.
      Sociodemographic, behavioral, and lifestyle variables were adjusted, and
      inadequate total sleep time (<7 hours) and snoring (yes/no) showed significant
      association with chronic disease status (risk ratio = 1.11, 95% confidence
      interval 1.00-1.22 and risk ratio = 1.20, 95% confidence interval 1.11-1.29,
      respectively). CONCLUSION: Inadequate sleep and snoring are independently
      associated with chronic disease in Bangladeshi adult population and perhaps
      elsewhere.

PMID- 29332680
TI  - Sleep disorders + Pregnancy=Possibility of decreasing preterm births.

PMID- 29332679
TI  - Socioeconomic status in childhood predicts sleep continuity in adult Black and
      White men.
AB  - OBJECTIVES: Low socioeconomic status (SES) in childhood may be associated with
      sleep in adulthood. We evaluated the relationships between SES in childhood
      through adolescence and into adulthood and sleep in midlife men. DESIGN:
      Prospective assessment of SES in childhood and adulthood. SETTING: Population
      based study of 139 Black and 105 White men enrolled since age 7 and evaluated for
      sleep characteristics at age 32. MEASUREMENTS: Actigraphy and diary measures of
      sleep duration, continuity, and quality for 1 week. Their parents reported their
      SES (a combination of educational attainment and occupational status) annually
      when the boys were ages 7 to 16. We estimated SES intercept (age 7) and slope
      (age 7 to 16) using M-Plus and conducted linear regression analyses using those
      values to predict adult sleep measures, adjusting for covariates. RESULTS: Men
      who had lower SES families at age 7, smaller increases in SES from ages 7 to 16,
      and lower SES in adulthood had more minutes awake after sleep onset. White men
      with greater increases in SES from ages 7 to 16 had shorter sleep. CONCLUSIONS:
      SES in childhood and improvement in SES through adolescence are related to sleep
      continuity in midlife men. To our knowledge, this is the first report using
      prospectively measured SES in childhood in relation to adult sleep.

PMID- 29332681
TI  - Sleep duration, sleep quality, and sexual orientation: findings from the 2013
      2015 National Health Interview Survey.
AB  - INTRODUCTION: This study identifies associations between sleep outcomes and
      sexual orientation net of sociodemographic and health-related characteristics,
      and produces estimates generalizable to the US adult population.
      PARTICIPANTS/METHODS: We used 2013-2015 National Health Interview Survey data
      (46,909 men; 56,080 women) to examine sleep duration and quality among straight,
      gay/lesbian, and bisexual US adults. Sleep duration was measured as meeting
      National Sleep Foundation age-specific recommendations for hours of sleep per
      day. Sleep quality was measured by 4 indicators: having trouble falling asleep,
      having trouble staying asleep, taking medication to help fall/stay asleep (all
      >=4 times in the past week), and having woken up not feeling well rested (>=4
      days in the past week). RESULTS: In the adjusted models, there were no
      differences by sexual orientation in the likelihood of meeting National Sleep
      Foundation recommendations for sleep duration. For sleep quality, gay men were
      more likely to have trouble falling asleep, to use medication to help fall/stay
      asleep, and to wake up not feeling well rested relative to both straight and
      bisexual men. Gay/lesbian women were more likely to have trouble staying asleep
      and to use medication to help fall/stay asleep relative to straight women.
      Finally, bisexual women were more likely to have trouble falling and staying
      asleep relative to straight women. CONCLUSIONS: Sexual minority women and gay men
      report poorer sleep quality compared with their straight counterparts.

PMID- 29332682
TI  - A provisional tool for the measurement of sleep satisfaction.
AB  - OBJECTIVES: The goal of this project was to provisionally identify the basic
      elements of sleep satisfaction within the general population. METHODS: The
      National Sleep Foundation conducted a systematic literature review and identified
      495 published articles evaluating potential indicators of sleep satisfaction. The
      National Sleep Foundation then convened an expert panel ("Panel"), provided full
      text articles and summaries, and used a modified RAND appropriateness method with
      three total rounds of voting to determine the appropriateness of indicators for
      sleep satisfaction. RESULTS: The literature review revealed no tools or measures
      of sleep satisfaction (not dissatisfaction) applied to the general population and
      directly associated with good health. Nonetheless, a variety of sleep factors
      were extracted from the extant sleep research literature. Panel members voted on
      these indicators: sleep environmental factors; and sleep initiation and
      maintenance parameters. Using these indicators, the Panel constructed provisional
      questions for measuring sleep satisfaction. CONCLUSIONS: The Panel determined
      that appropriate sleep satisfaction elements include how an individual feels (a)
      about their sleep, (b) immediately after their sleep, and (c) during the
      subsequent day. Additionally, appropriate environmental elements include (a)
      bedding comfort, (b) bedroom temperature, and (c) noise and light in the bedroom.
      How one feels with (a) the time it takes to fall asleep, (b) the ease with which
      one falls back to sleep after awakening during a sleep period, (c) the amount of
      sleep on weekdays and weekends, as well as how undisturbed one's sleep is also
      were determined to be appropriate contributors to sleep satisfaction. Finally,
      the Panel agreed that whether an individual desired to change anything about
      their sleep, is a relevant question.

PMID- 29332683
TI  - Insomnia in primary care-a study from India.
AB  - OBJECTIVES: To study the prevalence and clinical correlates of insomnia among a
      sample of primary care attendees, in the state of Kerala, India. DESIGN: Cross
      sectional survey. SETTING: Primary care. PARTICIPANTS: 7017 adult patients [18-60
      years] attending 71 primary health centers selected by cluster random sampling.
      MEASUREMENTS: Patients were assessed for insomnia using the Insomnia Severity
      Index. In addition to self-reported socio-demographic and chronic medical illness
      details, structured instruments were used to assess for mental disorders,
      disability and life satisfaction. RESULTS: Subclinical insomnia and clinical
      insomnia were reported by 17.7% and 4.7% subjects, respectively. Subjects with
      subclinical and clinical insomnia when compared to those without insomnia had
      higher odds of having older age, female gender, urban background, lower
      education, chronic medical and mental disorders, greater disability and poor life
      satisfaction. Subjects with clinical insomnia when compared to the subclinical
      group had higher odds of having older age, urban background, lower education,
      mental disorders and greater disability. Among mental disorders, depressive
      disorder was correlated with both clinical and subclinical insomnia. CONCLUSIONS:
      Clinical and subclinical insomnia is common among primary care attendees and both
      are associated with significant morbidity. This study highlights that it is a
      major public health concern, albeit neglected, which needs to be dealt as a
      priority.

PMID- 29332685
TI  - Sleep patterns in children differ by ethnicity: cross-sectional and longitudinal
      analyses using actigraphy.
AB  - OBJECTIVES: To determine whether sleep patterns (duration, timing, efficiency)
      differ by ethnicity. DESIGN: Longitudinal study. SETTING: Dunedin, New Zealand.
      PARTICIPANTS: A total of 939 children (48% male) aged 4-12 years (572 European,
      181 Maori, 111 Pacific, 75 Asian). MEASUREMENTS: All measurements were obtained
      at months 0, 12, and 24. Anthropometry was obtained using standard techniques,
      and parents completed questionnaires assessing demographics, dietary intake, and
      television habits of children. Sleep and physical activity were measured using
      Actigraph accelerometers over 1 week. Differences in sleep outcomes according to
      ethnicity were adjusted for demographics, weight status, and behavioral variables
      using mixed models. RESULTS: Pacific children had greater body mass index and
      were more likely to live in deprived areas than children from other ethnic groups
      (all P<.001), but few differences were observed in behavioral variables. Pacific
      Island children slept 16 (95% confidence interval, 7-25) minutes less per night
      than New Zealand European children, predominantly as a result of later bedtimes
      (29; 20-38 minutes). By contrast, sleep efficiency did not differ by ethnicity or
      over time (all P>=.118). Maori children did not show the same relative deficits
      in sleep, displaying similar results to European children. Sleep duration
      decreased by 8 minutes (95% confidence interval, 6-10) a night each year over 2
      years, and change over time did not differ by ethnicity (all P>=.165).
      CONCLUSIONS: From a young age, Pacific children had poorer sleep patterns than
      European children, and these patterns were maintained over 2 years.

PMID- 29332684
TI  - Racial/ethnic sleep disparities in US school-aged children and adolescents: a
      review of the literature.
AB  - Sleep is essential for optimal health, well-being, and cognitive functioning, and
      yet nationwide, youth are not obtaining consistent, adequate, or high-quality
      sleep. In fact, more than two-thirds of US adolescents are sleeping less than 8
      hours nightly on school nights. Racial and ethnic minority children and
      adolescents are at an increased risk of having shorter sleep duration and poorer
      sleep quality than their white peers. In this review, we critically examined and
      compared results from 23 studies that have investigated racial/ethnic sleep
      disparities in American school-aged children and adolescents ages 6-19 years. We
      found that White youth generally had more sufficient sleep than minority youth,
      Hispanics had more than Blacks, and there was inconclusive evidence for Asians
      and other minorities. Recommendations for researchers include the following: (1)
      explore underlying causes of the disparities of these subpopulations, with a
      particular interest in identifying modifiable causes; (2) examine factors that
      may be impacted by racial/ethnic sleep disparities; (3) use a multidimensional
      approach to measuring sleep disparities; and (4) examine how beliefs about sleep
      are patterned by race/ethnicity. Understanding sleep disparities can inform
      interventions, policies, and educational programs to minimize sleep disparities
      and their impact on health, psychological, and educational outcomes.

PMID- 29332686
TI  - No evidence for an epidemiological transition in sleep patterns among children: a
      12-country study.
AB  - OBJECTIVE: To examine the relationships between socioeconomic status (SES;
      household income and parental education) and objectively measured sleep patterns
      (sleep duration, sleep efficiency, and bedtime) among children from around the
      world and explore how the relationships differ across country levels of human
      development. DESIGN: Multinational, cross-sectional study from sites in
      Australia, Brazil, Canada, China, Colombia, Finland, India, Kenya, Portugal,
      South Africa, the United Kingdom, and the United States. SETTING: The
      International Study of Childhood Obesity, Lifestyle and the Environment.
      PARTICIPANTS: A total of 6040 children aged 9-11 years. MEASUREMENTS: Sleep
      duration, sleep efficiency, and bedtime were monitored over 7 consecutive days
      using waist-worn accelerometers. Multilevel models were used to examine the
      relationships between sleep patterns and SES. RESULTS: In country-specific
      analyses, there were no significant linear trends for sleep duration and sleep
      efficiency based on income and education levels. There were significant linear
      trends in 4 countries for bedtime (Australia, United States, United Kingdom, and
      India), generally showing that children in the lowest income group had later
      bedtimes. Later bedtimes were associated with lowest level of parental education
      in only 2 countries (United Kingdom and India). Patterns of associations between
      sleep characteristics and SES were not different between boys and girls.
      CONCLUSIONS: Sleep patterns of children (especially sleep duration and
      efficiency) appear unrelated to SES in each of the 12 countries, with no
      differences across country levels of human development. The lack of evidence for
      an epidemiological transition in sleep patterns suggests that efforts to improve
      sleep hygiene of children should not be limited to any specific SES level.

PMID- 29332688
TI  - Corrigendum to "Interaction between bacterial cell membranes and nano-TiO2
      revealed by two-dimensional FTIR correlation spectroscopy using bacterial ghost
      as a model cell envelope" [Water Res. 118 (2017) 104-113].

PMID- 29332687
TI  - Similarities and differences in estimates of sleep duration by polysomnography,
      actigraphy, diary, and self-reported habitual sleep in a community sample.
AB  - OBJECTIVES: To compare estimates of sleep duration defined by polysomnography
      (PSG), actigraphy, daily diary, and retrospective questionnaire and to identify
      characteristics associated with differences between measures. DESIGN: Cross
      sectional. SETTING: Community sample. PARTICIPANTS: The sample consisted of 223
      Black, White, and Asian middle- to older-aged men and women residing in the
      Pittsburgh, PA area. INTERVENTIONS: Not applicable. MEASUREMENTS: Two nights of
      in-home PSG; 9 nights of wrist actigraphy and sleep diaries; retrospective sleep
      questionnaires; and measures of sociodemographic, psychosocial, and adiposity
      characteristics. RESULTS: All measures of sleep duration differed significantly,
      with modest associations between PSG-assessed and retrospective questionnaire
      assessed sleep duration. Individuals estimated their habitual sleep duration
      about 20-30 minutes longer by questionnaire and their prospective sleep diaries
      compared with both PSG- and actigraphy-assessed sleep duration. Persons reporting
      higher hostility had smaller associations between PSG-assessed sleep duration and
      other methods compared with those with lower hostility; those reporting more
      depressive symptoms and poorer overall health had smaller associations between
      actigraphy-assessed sleep duration and questionnaire and diary measures. Apnea
      hypopnea index was not related to differences among estimates of sleep duration.
      CONCLUSIONS: PSG, actigraphy, diary, and retrospective questionnaire assessments
      yield different estimates of sleep duration. Hostility, depressive symptoms, and
      perceptions of poor health were associated with the magnitude of differences
      among some estimates. These findings may be useful in understanding the health
      consequences of short or long self-reported sleep duration and for guiding
      investigator decisions about choices of measures in specific populations.

PMID- 29332690
TI  - Editorial.

PMID- 29332689
TI  - Corrigendum to "Pesticides drive risk in wastewater-impacted streams during low
      flow conditions " [Water Res. 110 (2017) 366-377].

PMID- 29332691
TI  - Ink dating, part I: Statistical distribution of selected ageing parameters in a
      ballpoint inks reference population.
AB  - The development of ink dating methods requires an important amount of work in
      order to be reliably applicable in practice. Major tasks include the definition
      of ageing parameters to monitor ink ageing. An adequate parameter should ideally
      fulfil the following criteria: it should evolve as a function of time in a
      monotonic way, be measurable in a majority of ink entries, be as accurate and
      reproducible as possible, and finally it should not be influenced too much by
      transfer and storage conditions. This work aimed at evaluating the potential of
      seven ageing parameters for ink dating purposes: the phenoxyethanol quantity,
      relative peak areas (RPA), three solvent loss ratios (R%, R%*, NR%) and two
      solvent loss parameters (RNORM, NRNORM). These were calculated over approximately
      one year for 25 inks selected from a large database to represent different ageing
      behaviours. Ink entries were analysed using liquid extraction followed by GC/MS
      analysis. Results showed that natural ageing parameters (NR% and NRNORM) were not
      suitable ageing parameters for ink entries older than a few weeks. RPA used other
      compounds present in ink formulations in combination to PE in order to normalise
      the results. However, it presented particular difficulties as they could not be
      defined for all inks and were thus applicable only for 64% of the studied inks.
      Finally, the PE quantity, R% and RNORM allowed to follow the ageing of the
      selected inks over the whole time frame and were identified as the most
      promising. These were thus selected to test three different interpretation models
      in the second part of this article. The possibilities and limitations of ink
      dating methods will be discussed in a legal perspective.

PMID- 29332692
TI  - Dead weight: Validation of mass regression equations on experimentally burned
      skeletal remains to assess skeleton completeness.
AB  - In very fragmentary remains, the thorough inventory of skeletal elements is often
      impossible to accomplish. Mass has been used instead to assess the completeness
      of the skeleton. Two different mass-based methods of assessing skeleton
      completeness were tested on a sample of experimentally burned skeletons with the
      objective of determining which of them is more reliable. The first method was
      based on a simple comparison of the mass of each individual skeleton with
      previously published mass references. The second method was based on mass linear
      regressions from individual bones to estimate complete skeleton mass. The
      clavicle, humerus, femur, patella, metacarpal, metatarsal and tarsal bones were
      used. The sample was composed of 20 experimentally burned skeletons from 10 males
      and 10 females with ages-at-death between 68 and 90years old. Results
      demonstrated that the regression approach is more objective and more reliable
      than the reference comparison approach even though not all bones provided
      satisfactory estimations of the complete skeleton mass. The femur, humerus and
      patella provided the best performances among the individual bones. The
      estimations based on the latter had root mean squared errors (RMSE) smaller than
      300g. Results demonstrated that the regression approach is quite promising
      although the patella was the only reasonable predictor expected to survive
      sufficiently intact to a burning event at high temperatures. The mass comparison
      approach has the advantage of not depending on the preservation of individual
      bones. Whenever bones are intact though, the application of mass regressions
      should be preferentially used because it is less subjective.

PMID- 29332693
TI  - Ink dating part II: Interpretation of results in a legal perspective.
AB  - The development of an ink dating method requires an important investment of
      resources in order to step from the monitoring of ink ageing on paper to the
      determination of the actual age of a questioned ink entry. This article aimed at
      developing and evaluating the potential of three interpretation models to date
      ink entries in a legal perspective: (1) the threshold model comparing analytical
      results to tabulated values in order to determine the maximal possible age of an
      ink entry, (2) the trend tests that focusing on the "ageing status" of an ink
      entry, and (3) the likelihood ratio calculation comparing the probabilities to
      observe the results under at least two alternative hypotheses. This is the first
      report showing ink dating interpretation results on a ballpoint be ink reference
      population. In the first part of this paper three ageing parameters were selected
      as promising from the population of 25 ink entries aged during 4 to 304days: the
      quantity of phenoxyethanol (PE), the difference between the PE quantities
      contained in a naturally aged sample and an artificially aged sample (RNORM) and
      the solvent loss ratio (R%). In the current part, each model was tested using the
      three selected ageing parameters. Results showed that threshold definition
      remains a simple model easily applicable in practice, but that the risk of false
      positive cannot be completely avoided without reducing significantly the
      feasibility of the ink dating approaches. The trend tests from the literature
      showed unreliable results and an alternative had to be developed yielding
      encouraging results. The likelihood ratio calculation introduced a degree of
      certainty to the ink dating conclusion in comparison to the threshold approach.
      The proposed model remains quite simple to apply in practice, but should be
      further developed in order to yield reliable results in practice.

PMID- 29332694
TI  - Score based procedures for the calculation of forensic likelihood ratios - Scores
      should take account of both similarity and typicality.
AB  - Score based procedures for the calculation of forensic likelihood ratios are
      popular across different branches of forensic science. They have two stages,
      first a function or model which takes measured features from known-source and
      questioned-source pairs as input and calculates scores as output, then a
      subsequent model which converts scores to likelihood ratios. We demonstrate that
      scores which are purely measures of similarity are not appropriate for
      calculating forensically interpretable likelihood ratios. In addition to taking
      account of similarity between the questioned-origin specimen and the known-origin
      sample, scores must also take account of the typicality of the questioned-origin
      specimen with respect to a sample of the relevant population specified by the
      defence hypothesis. We use Monte Carlo simulations to compare the output of three
      score based procedures with reference likelihood ratio values calculated directly
      from the fully specified Monte Carlo distributions. The three types of scores
      compared are: 1. non-anchored similarity-only scores; 2. non-anchored similarity
      and typicality scores; and 3. known-source anchored same-origin scores and
      questioned-source anchored different-origin scores. We also make a comparison
      with the performance of a procedure using a dichotomous "match"/"non-match"
      similarity score, and compare the performance of 1 and 2 on real data.

PMID- 29332695
TI  - Variation of delta2H, delta18O & delta13C in crude palm oil from different
      regions in Malaysia: Potential of stable isotope signatures as a key traceability
      parameter.
AB  - A total of 33 crude palm oil samples were randomly collected from different
      regions in Malaysia. Stable carbon isotopic composition (delta13C) was determined
      using Flash 2000 elemental analyzer while hydrogen and oxygen isotopic
      compositions (delta2H and delta18O) were analyzed by Thermo Finnigan TC/EA,
      wherein both instruments were coupled to an isotope ratio mass spectrometer. The
      bulk delta2H, delta18O and delta13C of the samples were analyzed by Hierarchical
      Cluster Analysis (HCA), Principal Component Analysis (PCA) and Orthogonal Partial
      Least Square-Discriminant Analysis (OPLS-DA). Unsupervised HCA and PCA methods
      have demonstrated that crude palm oil samples were grouped into clusters
      according to respective state. A predictive model was constructed by supervised
      OPLS-DA with good predictive power of 52.60%. Robustness of the predictive model
      was validated with overall accuracy of 71.43%. Blind test samples were correctly
      assigned to their respective cluster except for samples from southern region.
      delta18O was proposed as the promising discriminatory marker for discerning crude
      palm oil samples obtained from different regions. Stable isotopes profile was
      proven to be useful for origin traceability of crude palm oil samples at a
      narrower geographical area, i.e. based on regions in Malaysia. Predictive power
      and accuracy of the predictive model was expected to improve with the increase in
      sample size. Conclusively, the results in this study has fulfilled the main
      objective of this work where the simple approach of combining stable isotope
      analysis with chemometrics can be used to discriminate crude palm oil samples
      obtained from different regions in Malaysia. Overall, this study shows the
      feasibility of this approach to be used as a traceability assessment of crude
      palm oils.

PMID- 29332696
TI  - A comparison of plastic cable ties based on physical, chemical and stable
      isotopic measurements.
AB  - Plastic cable ties can be utilised in a range of serious criminal activities and
      a comparison of cable ties, or fragments, may form part of the physical evidence
      presented to a Court of law. This research assessed the potential value of
      evidence based on the analysis of plastic cable ties. Twenty packets of black
      coloured plastic cable ties (nominally 200mm*4.8mm) were purchased in pack sizes
      ranging from 25 to 100 individual cable ties (Brisbane, Australia, March 2015).
      Representative samples from each packet were visually examined, compared and
      tested to determine their physical dimensions, chemical compositions and stable
      isotopic compositions (delta2H, delta13C and delta15N). All of the individual
      cable ties from a given packet were found to be indistinguishable with respect to
      appearance, physical, chemical and isotopic measurements (within-batch
      variability). Individual cable ties were also found to be isotopically
      homogeneous with respect to hydrogen, carbon and nitrogen. All of the cable ties
      analysed were found to have very similar chemical compositions and to be
      manufactured predominantly from nylon 6,6. The elemental compositions of
      composite samples, prepared from each packet, were found to be highly variable
      and, as such, were of very limited value. Cable ties from ten of the twenty
      packets were uniquely characterised by physical appearance (between-batch
      variability). Physical measurements such as the width, thickness and tooth-count
      of the grip section did not provide additional discrimination. Cable ties from
      nineteen of the twenty packets were uniquely characterised by isotopic
      composition, based on delta2H and delta15N measurements. Samples from two packets
      of Crescent brand cable ties were found to be indistinguishable with respect to
      all of the tests applied in this study. These two packets were inadvertently
      purchased from the same retailer and had the same barcode and batch number. It
      was considered a reasonable assumption that these two packets originated from the
      same manufacturing batch. The authors reason that a likelihood ratio (that might
      be presented to a Court of law) can be derived from this type of discrete data
      based on a calculation of the possible combinations of distinguishable objects
      (unordered sampling with replacement) in a convenience sample collected from the
      background population. In this example, a database of 19 distinguishable objects
      can yield a likelihood ratio as high as 210, with a verbal equivalent of
      "moderately strong support" for a proposition that two cable ties have the same
      isotopic composition because they originate from the same batch rather than by
      random chance.

PMID- 29332698
TI  - Response to "A study of the perception of verbal expressions of the strength of
      evidence".

PMID- 29332697
TI  - Acid alteration of several ignitable liquids of potential use in arsons.
AB  - Ignitable liquids such as fuels, alcohols and thinners can be used in criminal
      activities, for instance arsons. Forensic experts require to know their chemical
      compositions, as well as to understand how different modification effects could
      impact them, in order to detect, classify and identify them properly in fire
      debris. The acid alteration/acidification of ignitable liquids is a modification
      effect that sharply alters the chemical composition, for example, of gasoline and
      diesel fuel, interfering in the forensic analysis and result interpretation.
      However, to date there is little information about the consequences of this
      effect over other accelerants of interests. In this research paper, the
      alteration by sulfuric acid of several commercial thinners and other accelerants
      of potential use in arsons is studied in-depth. For that purpose, spectral (by
      ATR-FTIR) and chromatographic (by GC-MS) data were obtained from neat and
      acidified samples. Then, the spectral and chromatographic modifications of each
      studied ignitable liquid were discussed, proposing several chemical mechanisms
      that explain the new by-products produced and the gradual disappearance of the
      initial compounds. Hydrolysis, Fischer esterification and alkylation reactions
      are involved in the modification of esters, alcohols, ketones and aromatic
      compounds of the studied ignitable liquids. This information could be crucial for
      correctly identifying these accelerants. Additionally, an exploratory analysis
      revealed that some of the most altered ignitable liquid samples might be very
      similar with each other, which could have impact on casework.

PMID- 29332699
TI  - Aiding the interpretation of forensic gait analysis: Development of a features of
      gait database.

PMID- 29332700
TI  - Corrigendum to "Preventing miscarriages of justice: A review of forensic firearm
      identification" [Sci. Justice 56 (2) (2016) 129-142].

PMID- 29332701
TI  - Editor's Perspectives - January 2018.

PMID- 29332702
TI  - 2018, a turning point for the Archives de Pediatrie.

PMID- 29332703
TI  - Commentary from the Editor.

PMID- 29332704
TI  - Cutaneous squamous cell carcinoma: Incidence, risk factors, diagnosis, and
      staging.
AB  - Cutaneous squamous cell carcinoma (cSCC), a malignant proliferation of cutaneous
      epithelium, represents 20% to 50% of skin cancers. Although the majority of cSCCs
      are successfully eradicated by surgical excision, a subset of cSCC possesses
      features associated with a higher likelihood of recurrence, metastasis, and
      death. The proper identification of these aggressive cSCCs can guide additional
      work-up and management. In the first article in this continuing medical education
      series, we discuss the incidence, recurrence rates, mortality rates, and risk
      factors associated with cSCC and review the staging systems used to stratify
      patients into high- and low-risk groups. The second article in this series
      reviews the treatment options for cSCC, with focused attention on the management
      of high-stage tumors.

PMID- 29332705
TI  - Cutaneous squamous cell carcinoma: Management of advanced and high-stage tumors.
AB  - While the majority of cutaneous squamous cell carcinomas (cSCCs) can be treated
      surgically, the additional work-up and treatments indicated for high-risk cSCC
      remain undefined. In recent years, improvements in tumor staging systems have
      allowed for the more accurate stratification of tumors into high- and low-risk
      categories. This insight, along with the publication of cSCC guidelines, brings
      us closer to the development of a consensus approach. The second article in this
      continuing medical education series addresses in question and answer format the
      most common questions related to advanced and high-stage cSCCs, with a simplified
      flowchart. The questions include the following: 1) Does my patient have high-risk
      cSCC?; 2) What is the next step for patients with cSCC and palpable
      lymphadenopathy?; 3) In patients with no clinically evident lymphadenopathy, who
      are candidates for lymph node staging?; 4) What forms of radiologic imaging can
      help detect subclinical lymph node metastases?; 5) What is the role of sentinel
      lymph node biopsy in cSCC?; 6) Which patients with cSCC need adjuvant radiation
      therapy?; 7) Is adjuvant chemotherapy an option for patients with high-stage cSCC
      after surgery?; 8) Are targeted and immunologic therapies an option for advanced
      cSCC?; 9) How often should I follow up with my patient after he/she has been
      diagnosed with a high-risk cSCC?; 10) What are the options for chemoprophylaxis
      in a patient with an increased risk of cSCC?; and 11) What chemopreventive
      measures can be started in coordination with medical oncology or transplant
      physicians?

PMID- 29332706
TI  - Skin mapping for the classification of generalized morphea.
AB  - BACKGROUND: Generalized morphea lacks cohesive clinical features, limiting its
      clinical and investigative utility. OBJECTIVE: We sought to use computerized
      lesion mapping to objectively subtype morphea. METHODS: We conducted a 2-part
      cross-sectional study. In part 1, we created a discovery cohort of patients with
      generalized morphea of whom lesion maps were created to characterize subsets.
      Clinical and demographic features were compared between proposed subsets to
      determine if they identified clinically relevant differences. In part 2, we
      created a validation cohort to determine if proposed criteria were applicable to
      different individuals. RESULTS: A total of 123 patients with generalized morphea
      were included. Mapping produced 2 distribution patterns that encompassed the
      majority in both cohorts: isomorphic (areas of skin friction) and symmetric
      (symmetrically distributed on trunk/extremities). In the discovery cohort, the
      isomorphic subset was older (55.6 +/- 12.7 vs 42.2 +/- 20.1 years, P < .001), all
      female (30/30 vs 38/43, P = .05), and more often had lichen sclerosus changes
      (12/43 vs 8/43, P = .02); involvement of the reticular dermis, subcutaneous fat,
      and/or fascia was more common in symmetric (10/43 vs 1/30) (P = .02). These
      features persisted in the validation cohort. LIMITATIONS: Single cohort was a
      limitation. CONCLUSIONS: Symmetric and isomorphic subsets possess distinctive
      demographic and clinical features, suggesting they more accurately define the
      phenotype of generalized morphea. Consideration should be given to revising
      classification.

PMID- 29332707
TI  - Cutaneous hemophagocytosis: Clinicopathologic features of 21 cases.
AB  - BACKGROUND: Hemophagocytosis is well known in cytotoxic cutaneous T-cell
      lymphomas (CTCLs), in which it may represent a sign of hemophagocytic
      lymphohistiocytosis syndrome (HLHS), and is also typical of cutaneous Rosai
      Dorfman disease (cRDD) (without prognostic relevance). Only rarely, has cutaneous
      hemophagocytosis (CH) been described in other skin conditions. OBJECTIVE: To
      characterize the clinicopathologic features of CH in skin biopsy specimens from
      patients with conditions other than CTCL or cRDD. METHODS: Case series analyzing
      clinicopathologic features and follow-up data on patients presenting with
      histopathologic signs of CH. RESULTS: Biopsy specimens from 21 patients were
      included. None of the patients had HLHS. The majority (n = 11) presented with
      leukocytoclastic vasculitis. Other associated diseases were lupus erythematous (n
      = 2), arthropod bite reaction (n = 2), erysipelas (n = 1), acne conglobata (n =
      1), and Sweet syndrome (n = 1). Three patients had a nonspecific rash concomitant
      with Chlamydia pneumonia, middle ear infection, and pharyngitis, respectively.
      LIMITATIONS: This was a single-center, retrospective study. CONCLUSION: Isolated
      CH in conditions other than CTCL and cRDD is a histopathologic finding related
      mostly to leukocytoclastic vasculitis. Extensive investigations should be
      performed only if patients have other signs or symptoms of HLHS.

PMID- 29332709
TI  - Epidemiology of staphylococcal scalded skin syndrome in the United States: A
      cross-sectional study, 2010-2014.

PMID- 29332710
TI  - Socioeconomic and geographic barriers to dermatology care in urban and rural US
      populations.

PMID- 29332708
TI  - Management of psoriasis in patients with inflammatory bowel disease: From the
      Medical Board of the National Psoriasis Foundation.
AB  - BACKGROUND: There is a significant association between psoriasis and inflammatory
      bowel disease (IBD). Many treatments for psoriasis and psoriatic arthritis are
      also used for IBD. OBJECTIVE: To assess therapeutic options for patients with
      psoriasis and concurrent IBD. METHODS: A systematic literature search was
      performed for clinical studies of biologic and systemic psoriasis medications in
      psoriasis, psoriatic arthritis, ulcerative colitis, and Crohn's disease, for the
      period from January 1, 1947, to February 14, 2017. Randomized, controlled, double
      blinded studies were selected if available. If not, the next highest level of
      available evidence was selected. RESULTS: Of the 2282 articles identified, 132
      were selected. Infliximab and adalimumab have demonstrated efficacy in psoriasis,
      psoriatic arthritis, ulcerative; colitis, and Crohn's disease. Ustekinumab has
      demonstrated efficacy in psoriasis, psoriatic arthritis, and Crohn's disease.
      Certolizumab has demonstrated efficacy in psoriatic arthritis and Crohn's
      disease. Etanercept, secukinumab, brodalumab, and ixekizumab have demonstrated
      efficacy in psoriasis and psoriatic arthritis but may exacerbate or induce IBD.
      Guselkumab has demonstrated efficacy in psoriasis. LIMITATIONS: There are no
      known clinical trials of treatment specifically for concurrent psoriasis and IBD.
      CONCLUSIONS: Infliximab and adalimumab have demonstrated efficacy in psoriasis,
      psoriatic arthritis, ulcerative colitis, and Crohn's disease; other agents have
      demonstrated efficacy for some, but not all, of these indications.

PMID- 29332711
TI  - Very low-dose versus standard dose radiation therapy for indolent primary
      cutaneous B-cell lymphomas: A retrospective study.

PMID- 29332712
TI  - Differences between recruitment advertisements for academic and private practice
      dermatologists.

PMID- 29332713
TI  - Fissured tongue in patients with psoriasis.

PMID- 29332714
TI  - Oral green tea catechins do not provide photoprotection from direct DNA damage
      induced by higher dose solar simulated radiation: A randomized controlled trial.

PMID- 29332715
TI  - Prevalence of gastrointestinal comorbidities in rosacea: Comparison of
      subantimicrobial, modified release doxycycline versus conventional release
      doxycycline.

PMID- 29332717
TI  - Patch testing for nonimmediate cutaneous adverse drug reactions.

PMID- 29332716
TI  - Predicting the incidence and timing of central nervous system disease in
      metastatic melanoma: Implications for surveillance and preventative therapy.

PMID- 29332718
TI  - Accuracy of death certification in cutaneous squamous cell carcinoma: A
      retrospective case review.

PMID- 29332719
TI  - The ethics of volunteerism: Whose cultural and ethical norms take precedence?

PMID- 29332720
TI  - Commentary: The ethics of volunteerism: Whose cultural and ethical norms take
      precedence?

PMID- 29332721
TI  - Oral isotretinoin as an adjunctive treatment for recurrent genital warts.

PMID- 29332722
TI  - From laboratory to operating room: Innovative use of manual blood cell counting
      machine for counting follicular grafts.

PMID- 29332723
TI  - A method using simple stitches around the safety margin for hemostasis in scalp
      surgery.

PMID- 29332724
TI  - Reply to: "Tofacitinib for the treatment of severe alopecia areata and variants".

PMID- 29332725
TI  - In reply.

PMID- 29332726
TI  - Histopathology of facial papules in frontal fibrosing alopecia and therapeutic
      response to oral isotretinoin.

PMID- 29332727
TI  - Reply to: "Histopathology of facial papules in frontal fibrosing alopecia and
      therapeutic response to oral isotretinoin".

PMID- 29332728
TI  - Is the setting sun dermoscopic pattern specific to juvenile xanthogranuloma?

PMID- 29332729
TI  - Reply to: "Is the setting sun dermoscopic pattern specific to juvenile
      xanthogranuloma?"

PMID- 29332730
TI  - Biomechanical factors associated with running economy and performance of elite
      Kenyan distance runners: A systematic review.
AB  - BACKGROUND: Running economy (RE) is a determinant of performance in endurance
      sports and is a complex multi-factorial measure which reflects the combined
      functioning of bio-mechanical, neuro-muscular, metabolic and cardio-respiratory
      factors some of which are hereditary or adapt to coaching. Kenyan distance
      runners have dominated major global events with their unmatched performance for
      decades and this phenomenon has prompted several investigations aimed at
      establishing possible factors associated with their performance. This systematic
      review was aimed at establishing up-to date quantitative synthesis of evidence on
      biomechanical factors associated with running economy and performance of elite
      Kenyan distance runners and to provide an algorithm for future research and
      coaching strategies. METHODS: A comprehensive electronic search was conducted
      through June 2017. Quality appraisal was independently done by both reviewers
      using the STROBE checklist. Descriptive summaries and tables were used to
      illustrate biomechanical outcomes, mean differences and confidence intervals.
      Evidence from reviewed studies was graded according to the Australian National
      Health and Medical Research Council (NHMRC) hierarchy for aetiological factors
      and meta-analysis was performed where applicable. RESULTS: Eight cross-sectional
      studies were included. The overall methodological score was moderate (58%). Elite
      Kenyan distance runners have significant longer gastroc-Achilles tendons compared
      to their counterparts while their shank length is not significantly longer. There
      is no certainty of evidence regarding the association between their
      characteristic unique profile of tall and slender bodies, low BMI and low body
      mass, short ground contact and flight times, greater forward lean torso and
      faster and greater forward leg swing with RE and performance. CONCLUSION: Our
      findings presents evidence on biomechanical factors associated with RE and
      performance of elite Kenyan distance runners. Despite these findings, there are a
      number of limitations inherent to this review including; low level of evidence,
      minimal number of included studies, small sample size and lack of appropriate
      control subjects. However, we considered these shortcomings and summarised the
      best available evidence in attempt to give direction to future research and
      coaching strategies.

PMID- 29332731
TI  - Quantitative tissue parameters of Achilles tendon and plantar fascia in healthy
      subjects using a handheld myotonometer.
AB  - OBJECTIVE: The aim of the study was to examine the quantitative tissue properties
      of the Achilles tendon and plantar fascia using a handheld, non-invasive
      MyotonPRO device, in order to generate normal values and examine the
      biomechanical relationship of both structures. DESIGN: Prospective study of a
      large, healthy sample population. PARTICIPANTS: The study sample included 207
      healthy subjects (87 males and 120 females) for the Achilles tendon and 176
      healthy subjects (73 males and 103 females) for the plantar fascia. For the
      correlations of the tissue parameters of the Achilles tendon and plantar fascia
      an intersection of both groups was formed which included 150 healthy subjects (65
      males and 85 females). INTERVENTIONS: All participants were measured in a prone
      position. Consecutive measurements of the Achilles tendon and plantar fascia were
      performed by MyotonPRO device at defined sites. RESULTS: For the left and right
      Achilles tendons and plantar fasciae all five MyotonPRO parameters (Frequency
      [Hz], Decrement, Stiffness [N/m], Creep and Relaxation Time [ms]) were calculated
      of healthy males and females. The correlation of the tissue parameters of the
      Achilles tendon and plantar fascia showed a significant positive correlation of
      all parameters on the left as well as on the right side. CONCLUSIONS: The
      MyotonPRO is a feasible device for easy measurement of passive tissue properties
      of the Achilles tendon and plantar fascia in a clinical setting. The generated
      normal values of the Achilles tendon and plantar fascia are important for
      detecting abnormalities in patients with Achilles tendinopathy or plantar
      fasciitis in the future. Biomechanically, both structures are positively
      correlated. This may provide new aspects in the diagnostics and therapy of
      plantar fasciitis and Achilles tendinopathy.

PMID- 29332732
TI  - The science of respiratory characteristics in individuals with chronic low back
      pain: Interpreting through statistical perspective.

PMID- 29332733
TI  - A fundamental critique of the fascial distortion model and its application in
      clinical practice.
AB  - INTRODUCTION: The therapeutic techniques used in the fascial distortion model
      (FDM) have become increasingly popular among manual therapists and physical
      therapists. The reasons for this trend remain to be empirically explored.
      Therefore this paper pursues two goals: first, to investigate the historical and
      theoretical background of FDM, and second, to discuss seven problems associated
      with the theory and practice of FDM. MATERIALS AND METHODS: The objectives of
      this paper are based on a review of the literature. The research mainly focuses
      on clinical proofs of concept for FDM treatment techniques in musculoskeletal
      medicine. RESULTS: FDM as a treatment method was founded and developed in the
      early 1990s by Stephen Typaldos. It is based on the concept that all
      musculoskeletal complaints can be traced back to three-dimensional deformations
      or distortions of the fasciae. The concept is that these distortions can be
      undone through direct application of certain manual techniques. A literature
      review found no clinical trials or basic research studies to support the
      empirical foundations of the FDM contentions. DISCUSSION: Based on the absence of
      proof of concept for FDM treatment techniques along with certain theoretical
      considerations, seven problems emerge, the most striking of which include (1)
      diagnostic criteria for FDM, (2) the biological implausibility of the model, (3)
      the reduction of all such disorders to a single common denominator: the fasciae,
      (4) the role of FDM research, and (5) potentially harmful consequences related to
      FDM treatment. CONCLUSION: The above problems can only be invalidated through
      high-quality clinical trials. Allegations that clinical experience is sufficient
      to validate therapeutic results have been abundantly refuted in the literature.

PMID- 29332734
TI  - Correlation between cervical flexor muscle thickness and craniocervical flexion
      torque in healthy subjects.
AB  - The purpose of this study was to clarify the relationship between the size of the
      cervical flexor muscles and craniocervical (CC) flexion torque. Thirty-eight
      healthy men participated in this study. Thickness of the deep cervical flexor
      (DCF) and sternocleidomastoid (SM) muscles were measured using ultrasonography.
      Maximal isometric CC flexion torque was measured using dynamometry. The DCF and
      SM muscle thickness and CC flexion torque were normalized relative to body
      weight. Correlations between normalized muscle thickness and normalized CC
      flexion torque were determined. A significant positive correlation was observed
      between normalized DCF muscle thickness and normalized CC flexion torque (r =
      0.361, P = 0.028), whereas there was no significant correlation between
      normalized SM muscle thickness and normalized CC flexion torque (r = 0.233, P =
      0.166). DCF muscle thickness appears to have potential clinical application in
      the performance of CC flexion.

PMID- 29332735
TI  - Within-day and between-day reliability of thickness measurements of abdominal
      muscles using ultrasound during abdominal hollowing and bracing maneuvers.
AB  - Ultrasonography imaging has been used as a non-invasive method to estimate the
      thickness and relative activities of the abdominal muscles in patients with lower
      back pain (LBP). However, the statistical reliability of US thickness
      measurements of abdominal muscles, including transversus abdominis (TrA),
      internal oblique (IO) and external oblique (EO) muscles during abdominal
      hollowing (AH) and abdominal bracing (AB) maneuvers has not been well
      investigated. This study was performed on a total of 20 female subjects (10 with
      LBP and 10 without LBP) in the age range of 25-55 years to assess within-day and
      between-day reliability of the measurements. US measurements on maneuvers were
      repeated after two hours for the within-day reliability and after five days for
      the between-day reliability assessment. High intra-class correlation coefficient
      (ICC) values (>0.75) for within-day and between-day reliability assessments
      during AH maneuver were concluded. The ICC values were moderate for reliability
      assessment during AB. The ICC values for AH were greater than AB both for within-
      and between-day reliabilities. The small standard error of measurement and
      minimal detectable change values (0.16-0.78 and 0.44 to 2.15, respectively) were
      found for both AH and AB. We recommend real-time US imaging as a reliable way of
      determining the thicknesses of the TrA and IO muscle (and to some extent, EO
      muscle) for both healthy and LBP patients.

PMID- 29332736
TI  - Electromyographic changes in muscles around the ankle and the knee joints in
      women accustomed to wearing high-heeled or low-heeled shoes.
AB  - OBJECTIVES: This study aimed to investigate muscle activities in the muscles
      around the ankle and knee joints in women accustomed to wearing high-heeled or
      low-heeled shoes. METHODOLOGY: Forty young women (age: 18-40 years) participated
      in this comparative clinical study. Twenty of the recruited subjects were
      accustomed to high-heeled shoes and the other half to low-heeled shoes.
      Electrical activities of the ankle and knee muscles in both groups with and
      without wearing their accustomed shoes were studied during walking. RESULTS:
      Tibialis anterior and the medial gastrocnemius muscles started contraction
      earlier in the high-heeled shoe group. The duration of medial gastrocnemius
      activity and the intensity of proneus longus activity were significantly more in
      the high-heeled shoe group. CONCLUSION: Wearing high-heeled shoe for a long time
      could result in over work of muscles such as medial gastrocnemius and proneus
      longus by increasing the duration or the intensity of their contractions during
      walking.

PMID- 29332737
TI  - Effect of a lateral glide mobilisation with movement of the hip on vibration
      threshold in healthy volunteers.
AB  - BACKGROUND: Mulligan's mobilisation-with-movement (MWM) techniques are proposed
      to achieve their clinical benefit via neurophysiological mechanisms. However,
      previous research has focussed on responses in the sympathetic nervous system
      only, and is not conclusive. An alternative measure of neurophysiological
      response to MWM is required to support or refute this mechanism of action.
      Recently, vibration threshold (VT) has been used to quantify changes in the
      sensory nervous system in patients experiencing musculoskeletal pain. OBJECTIVE:
      To investigate the effect of a lateral glide MWM of the hip joint on vibration
      threshold compared to a placebo and control condition in asymptomatic volunteers.
      METHODS: Fifteen asymptomatic volunteers participated in this single-blinded,
      randomised, within-subject, placebo, control design. Participants received each
      of three interventions in a randomised order; a lateral glide MWM of the hip
      joint into flexion, a placebo MWM, and a control intervention. Vibration
      threshold (VT) measures were taken at baseline and immediately after each
      intervention. Mean change in VT from baseline was calculated for each
      intervention and then analysed for between group differences using a one-way
      analysis of variance (ANOVA). RESULTS: A one-way ANOVA revealed no statistically
      significant differences between the three experimental conditions (P = 0.812).
      CONCLUSION: This small study found that a lateral glide MWM of the hip did not
      significantly change vibration threshold compared to a placebo and control
      intervention in an asymptomatic population. This study provides a method of using
      vibration threshold to investigate the potential neurophysiological effects of a
      manual therapy intervention that should be repeated in a larger, symptomatic
      population.

PMID- 29332738
TI  - Body composition estimation in children and adolescents by bioelectrical
      impedance analysis: A systematic review.
AB  - BACKGROUND: Bioelectrical impedance analysis (BIA) has commonly been used to
      assess the body composition of children and adolescents. BIA validation studies
      have found distinct correlation values with reference methods. OBJECTIVES: To
      assess the reproducibility, correlation and mean differences in body composition
      estimated by BIA and reference methods, we systematically reviewed the literature
      in the pediatric population. METHOD: The search for articles was conducted in
      March 2016 and was limited to articles published from 2005 to 2015 in the PubMed,
      Embase, EBSCO, Web of Science, Scopus and SciELO databases. Two reviewers
      independently performed data selection and extraction of studies that
      investigated the BIA validity, responsiveness, reliability and/or measurement
      error (reproducibility) to estimate body composition in children and adolescents
      with an average age <= 18 years. RESULTS: The search produced 48 articles. Almost
      perfect reproducibility was found in the body fat percentage estimated by BIA,
      and there was almost perfect correlation between the BIA ratings and reference
      methods for fat mass and fat-free mass. Regarding component estimates, BIA
      underestimated the fat mass in both sexes. CONCLUSIONS: The body fat percentage
      estimated by BIA exhibited almost perfect reproducibility. The fat mass and fat
      free mass estimated by BIA correlated almost perfectly with the reference methods
      in both sexes. BIA underestimated the fat mass in both sexes.

PMID- 29332739
TI  - Multifidus muscle size in adolescents with and without back pain using
      ultrasonography.
AB  - OBJECTIVE: The purposes of this study were; a) to compare multifidus muscle cross
      sectional area (CSA) in male adolescents suffering from low back pain (LBP) with
      healthy male adolescents using ultrasonography (US), and b) to assess the
      correlation between multifidus muscle size and demographic variables. METHODS: A
      random sample of 40 healthy boys (as a control group) and 40 boys with LBP (as an
      experimental group) at the age range of 15-18 years was recruited in the present
      cohort study. Multifidus muscle dimensions including CSA, antero-posterior and
      medio-lateral dimensions were measured at level of L5 in both groups using US.
      RESULTS: The results of an independent t-test to compare multifidus muscle size
      between the experimental and control groups showed a significant difference
      between the two groups in terms of CSA, antro-posterior and medio-lateral
      dimensions so that the experimental group had smaller muscle size than the
      control group. A significant correlation was found between height, weight and
      body mass index (BMI) and multifidus muscle size, but no significant correlation
      was observed between age and muscle size. Pain intensity and functional
      disability index was significantly correlated with muscle size in the
      experimental group. CONCLUSIONS: According to the results, multifidus muscle size
      was decreased in 15-18 years old male adolescents suffering from LBP compared
      with their healthy counterparts. Further studies are needed to support the
      findings of the present study.

PMID- 29332740
TI  - An electromyographic analysis of selected asana in experienced yogic
      practitioners.
AB  - The purpose of this study was to assess electromyographic (EMG) output of the
      anterior tibialis (TA), medial head of the gastrocnemius (GA), rectus femoris
      (RF), bicep femoris (BF), and gluteus medius (GM) in experienced yogic
      practitioners during selected yoga asana. A secondary purpose was to examine the
      differences in EMG output in unilateral V. bilateral standing yoga asana. The
      study was a single occasion descriptive design. Thirteen healthy yoga
      practitioners (1 male, 12 females, average age of 37.5) with more than five years
      of experience were recruited. EMG activity was recorded during maximum voluntary
      isometric contractions (MVIC) of the TA, GA, RF, and BF using the Biodex
      Multijoint System(r), and GM using manual muscle testing position. Subjects then
      performed the following yoga asana while EMG activity was recorded: downward
      facing dog, half-moon, tree, chair, and warrior three pose. Each asana was held
      for fifteen seconds and performed three times. EMG data were band pass filtered
      and the root mean square was obtained. Asana data were then amplitude normalized
      with the subjects' MVIC data. Integrated EMG was calculated for TA, GA, RF, BF
      and GM, in each asana. A multilevel regression analysis was performed, and peak
      EMG data was compared. Analysis between muscles showed that during CH and DD EMG
      activity was greatest in the TA muscle compared to the other muscles, while
      during HM and WR the GA muscle showed the greatest activity. Analysis within
      muscles showed low GA, BF, and GM activity during chair pose and downward facing
      dog compared to half moon, tree, and warrior three, and high RF activity during
      chair compared to the other poses. In conclusion, there were differences in
      frontal and sagittal plane muscle activation between single limb and double limb
      poses in experienced yogic practitioners.

PMID- 29332741
TI  - Abdominal and pelvic floor electromyographic analysis during abdominal
      hypopressive gymnastics.
AB  - INTRODUCTION: Abdominal hypopressive gymnastics appeared as an alternative to
      traditional abdominal exercises to promote abdominal muscles strength without
      overloading the pelvic floor muscles (PFM). To determine the activation level of
      abdominal muscles and PFM and the posture influence in the level of activation in
      these muscles during abdominal hypopressive gymnastics, we used surface
      electromyography in young and healthy multipara women. METHODS: This is an
      observational study with eutrophic nulliparous women aged between 18 and 35
      years, with abdominal skinfold less than or equal to 3 cm and active or
      irregularly active physical activity. Surface electromyography was used for
      rectus abdominis, external oblique, transversus abdominal/internal oblique
      (TrA/IO) and PFM assessment in the supine, quadruped and orthostatic (upright
      standing) positions during abdominal hypopressive gymnastics using normalized
      electromyographic (%EMG) data. We also analyzed the difference in activation
      between each muscle and between muscles and positions. RESULTS: Thirty women were
      evaluated and the mean age was 25.77 years (SD 3.29). The group formed by the
      TrA/IO muscles and the PFM showed higher %EMG in all the positions assessed,
      followed by the external oblique and rectus abdominis muscles. A comparison of
      %EMG of each muscle between the different positions showed differences only in
      rectus abdominis between the supine and quadruped (p = 0.001) and supine and
      orthostatic positions (p = 0.004), and in TrA/IO between the supine and
      orthostatic (p = 0.023) and orthostatic and quadruped positions (p = 0.019).
      CONCLUSIONS: The results suggest that abdominal hypopressive gymnastics can
      activate the abdominal muscles and PFM and the position do not have influence on
      electromyographic activation level of the PFM and external oblique.

PMID- 29332742
TI  - The effects of dorso-lumbar motion restriction on EMG activity of selected
      muscles during running.
AB  - : The effects of restricting dorso-lumbar spine mobility on electromyographic
      activity of the erector spinae, quadriceps femoris, hamstrings and gastrocnemius
      muscles in runners was investigated. Thermoplastic casting material was fashioned
      into a rigid orthosis and used to restrict spinal motion during running.
      Volunteers ran on a treadmill at 2.78 m/sec, under normal conditions and with
      spinal motion restricted. Surface electromyographic data was collected during
      both sets of trials. Normal electromyographic data was also compared with
      previous authors to determine similarity with their electromyographic data.
      RESULTS: Casted running resulted in an increase in erector spinae (p < 0.01) and
      quadriceps femoris (p = 0.02) electromyography activity. Total stride time and
      swing time of gait were decreased during casted running (p < 0.01), indicating a
      shift towards shorter and thus more frequent steps to run the same distance. The
      normal electromyographic data collected was in agreement with previously reported
      work. CONCLUSIONS: Neurological control over muscle and the fascia surrounding it
      is responsible for joint movement and load transfer. Experimentally restricting
      spinal motion during running demonstrated an increase in erector spinae and
      rectus femoris electromyographic activity. This lends support to the hypothesis
      that decreased spinal mobility may be a contributing factor to overuse muscle
      injuries in runners.

PMID- 29332743
TI  - Myoeletric indices of fatigue adopting different rest intervals during leg press
      sets.
AB  - INTRODUCTION: The purpose of this study was to examine the acute effect of
      different rest intervals between multiple sets of the 45 degrees  angled leg
      press exercise (LP45) on surface electromyographic (SEMG) spectral and amplitude
      indices of fatigue. METHODS: Fifteen recreationally trained females performed
      three protocols in a randomized crossover design; each consisting of four sets of
      10 repetitions with 1 (P1), 3 (P3), or 5 (P5) minute rest intervals between sets.
      Each set was performed with 70% of the LP45 ten-repetition maximum load. The SEMG
      data for biceps femoris (BF), vastus lateralis (VL), vastus medialis (VM), and
      rectus femoris (RF) muscles was then evaluated. RESULTS: The SEMG amplitude
      change in the time coefficient (CRMS) and spectral fatigue index (Cf5) indicated
      higher levels of fatigue for all muscles evaluated during the P3 protocol versus
      the P1 and P5 protocols (p <= 0.05), respectively. The RF and VL muscles showed
      greater fatigue levels by the second and third sets; whereas, greater fatigue was
      shown in the VM and BF muscles by the fourth set (p <= 0.05). CONCLUSIONS: A
      three-minute rest interval between sets might represent a neuromuscular window
      between a fatigue stated and fully recovered state in the context of neural
      activation. Moreover, a three minute rest interval between sets might allow for
      consistent recruitment of high threshold motor units over multiple sets, and thus
      promote a more effective stimulus for strength gains.

PMID- 29332744
TI  - How many physical therapy sessions are required to reach a good outcome in
      symptomatic lumbar spondylolisthesis? A retrospective study.
AB  - BACKGROUND: There is a lack of conclusive information about the optimal dosage of
      physical therapy treatments in Spondylolisthesis (SPL) patients. PURPOSE: The
      present study attempted to evaluate the comparative effectiveness of two
      different doses in reaching similar clinical outcomes. METHODS: A retrospective
      cohort study of 64 consecutive patients admitted for physical therapy with
      symptomatic lumbar grade I SPL (42 +/- 15years, 57% female) was conducted. At the
      end of the treatment, all participants were retrospectively assigned to one of
      two groups, receiving either 5-8 or 9-12 sessions (experimental or control group,
      respectively) of physical therapy treatments. The Prone Bridge Test (PBT) and the
      Supine Bridge Test (SBT) were used to measure muscular endurance. RESULTS: The
      area under the ROC curve for the PBT was 0.64 (95% CI 0.45-0.83) and for the SBT
      was 0.57 (95% CI 0.33-0.80). The optimal cutoff points were 25.5s for the PBT and
      55.0s for the SBT. Logistic regression revealed that PBT (OR = 1.062) was
      associated with SPL. The final regression model explained 77.4% (R2 = 0.341; p =
      0.024) of the variability. CONCLUSIONS: In this sample, the number of sessions
      required to achieve satisfactory outcomes ranged from 5 to 12. The clinical
      results of the subjects in the 5-8 sessions group were similar to the 9-12
      sessions group. Individual's coping mechanisms could be considered in future
      studies to understand which patients will require more therapeutic sessions.

PMID- 29332745
TI  - A critical overview of the current myofascial pain literature - January 2018.
AB  - The majority of papers included in the quarterly review discuss various aspects
      of dry needling (DN), which continues to be of interest to researchers and
      clinicians. A study by Liu et al. is the first paper to examine the effects of DN
      of acetylcholine, esterase and receptors. The study provides support for the
      integrated trigger point hypothesis and for DN. A paper by Hightower and
      colleagues found an intriguing link between low magnesium levels in the drink
      water supply, vitamin D, and myofascial pain, cancer, tendon ruptures, and colon
      polyps. Contributions originated in the Brazil, China, Germany, Iran, India,
      Poland, South Korea, Spain, Taiwan, Turkey, and the US.

PMID- 29332746
TI  - Is Pilates an effective rehabilitation tool? A systematic review.
AB  - BACKGROUND: Pilates is a system of exercise focusing upon controlled movement,
      stretching and breathing. Pilates is popular today not only for physical fitness
      but also for rehabilitation programs. This paper is a review of the literature on
      the effectiveness of Pilates as a rehabilitation tool in a wide range of
      conditions in an adult population. METHODS: A systematic literature review was
      carried out according to the PRISMA guidelines. Electronic databases were
      searched for cohort studies or randomised controlled trials (RCTs), and inclusion
      and exclusion criteria were applied. The final RCTs were assessed using the PEDro
      and CONSORT 2010 checklists. RESULTS: Twenty-three studies, published between
      2005 and 2016, met the inclusion criteria. These papers assessed the efficacy of
      Pilates in the rehabilitation of low back pain, ankylosing spondylitis, multiple
      sclerosis, post-menopausal osteoporosis, non-structural scoliosis, hypertension
      and chronic neck pain. Nineteen papers found Pilates to be more effective than
      the control or comparator group at improving outcomes including pain and
      disability levels. When assessed using the CONSORT and PEDro scales, the quality
      of the papers varied, with more falling toward the upper end of the scale.
      CONCLUSION: The majority of the clinical trials in the last five years into the
      use of Pilates as a rehabilitation tool have found it to be effective in
      achieving desired outcomes, particularly in the area of reducing pain and
      disability. It indicates the need for further research in these many areas, and
      especially into the benefits of particular Pilates exercises in the
      rehabilitation of specific conditions.

PMID- 29332747
TI  - Effects of spinal manipulation and myofascial techniques on heart rate
      variability: A systematic review.
AB  - BACKGROUND: The analysis of heart rate variability is important to the
      investigation of stimuli from the autonomic nervous system. Osteopathy is a form
      of treatment that can influence this system in healthy individuals as well as
      those with a disorder or disease. OBJECTIVES: The aim of the present study was to
      perform a systematic review of the literature regarding the effect of spinal
      manipulation and myofascial techniques on heart rate variability. METHODS:
      Searches were performed of the Pubmed, Scielo, Lilacs, PEDro, Ibesco, Cochrane
      and Scopus databases for relevant studies. The PEDro scale was used to assess the
      methodological quality of each study selected. RESULTS: A total of 505 articles
      were retrieved during the initial search. After an analysis of the abstracts,
      nine studies were selected for the present review. CONCLUSION: Based on the
      findings, osteopathy exerts an influence on the autonomic nervous system
      depending on the stimulation site and type. A greater parasympathetic response
      was found when stimulation was performed in the cervical and lumbar regions,
      whereas a greater sympathetic response was found when stimulation was performed
      in the thoracic region.

PMID- 29332748
TI  - The Pilates client on the hypermobility spectrum.

PMID- 29332749
TI  - Long-term effect of direction-movement control training on female patients with
      chronic neck pain.
AB  - BACKGROUND: Treatment of movement faults in the neck is known as an important
      factor in treatment of chronic neck pain. Along with the identification of site
      and direction of the faults, direction-movement control intervention retrains the
      control of the movement faults. PURPOSE: This study was designed to investigate
      long-term effects of a direction-movement control training on pain, disability,
      head repositioning accuracy, function, cervical flexor endurance, and range of
      motion in female patients with chronic nonspecific neck pain. MATERIAL AND
      METHODS: Thirty women (36.5 +/- 5.7 years) with chronic nonspecific neck pain
      were randomly allocated into two groups, i.e., an experimental group (n = 15) and
      a control group (n = 15). The experimental group performed the direction-movement
      control training for 30 min/day, three days per week for six months. All subjects
      were evaluated using the visual analog scale (VAS), range of motion (TOM),
      progressive iso-inertial lifting evaluation (PILE), neck disability Index (NDI),
      helmet attached with laser pointer using for head repositioning accuracy (HRA),
      and Trott's test (deep neck flexor endurance), in pre- and six-months post
      treatment intervention. RESULTS: Significant differences were observed for the
      pain, neck disability Index, function endurance, head repositioning accuracy,
      range of motion, and cervical flexor endurance in the experimental group compared
      to that of control group. CONCLUSION: Direction-movement control training is
      likely to be an effective training program to enhance body functionality through
      improvement of pain, function, endurance, head repositioning accuracy, range of
      motion, and cervical flexor endurance. Due to the high reported effect size for
      direction-movement control exercises, the application of the training is
      suggested as a supplementary method to improve chronic nonspecific neck pain in
      females.

PMID- 29332750
TI  - The influence of surface angle on muscle activity during Pilates based exercises.

PMID- 29332751
TI  - Gamification.

PMID- 29332752
TI  - The effects of neck mobilization in patients with chronic neck pain: A randomized
      controlled trial.
AB  - OBJECTIVE: To determine the effect of mobilization and routine physiotherapy on
      pain, disability, neck range of motion (ROM) and neck muscle endurance (NME) in
      patients having chronic mechanical neck pain (NP). METHODS: Sixty eight patients
      with chronic mechanical NP were randomly allocated into two groups by using a
      computer generated random sequence table with 34 patients in the multi-modal
      mobilization group and 34 patients in the routine physiotherapy group. Baseline
      values for pain, disability, NME, and neck ROM were recorded using visual
      analogue scale (VAS), neck disability index (NDI), neck flexor muscle endurance
      test and universal goniometer respectively, before the treatment. Each patient
      received 10 treatment sessions over a period of four weeks and at the end of four
      weeks all the outcome measures were recorded again. RESULTS: A paired t-test
      revealed significant pre to post treatment differences for all outcome measures
      in both groups (p <= 0.001 in all instances). An independent t-test revealed
      statistically significant differences for pain, disability, NME, and neck ROM in
      favor of the multi-modal mobilization group with a between group difference of
      1.57 cm for VAS (p < 0.001), 11.74 points for NDI (p = 0.001), 18.45 s for NME (p
      < 0.001) and 6.06-8.24 degrees  for neck ROM (p < 0.05). CONCLUSION: The results
      suggest that a combination of cervical mobilization with routine physiotherapy is
      more effective for reducing pain and disability and improving NME and neck ROM in
      patients with chronic mechanical NP compared to routine physiotherapy alone.

PMID- 29332753
TI  - Cognitive Functional Therapy (CFT) for chronic non-specific neck pain.
AB  - This case report presents the effect of Cognitive Functional Therapy (CFT) in a
      patient with chronic non-specific neck pain. The patient believed that pain
      signified tissue damage, and demonstrated pain catastrophizing, hypervigilance,
      stress sensitivity, and movement impairment of the neck, during extension and
      rotation. The CFT intervention integrated a cognitive approach with manual
      therapy and active exercises to encourage the patient to trust her neck again.
      One month after the first appointment, the patient had recovered confidence, and
      the pain and disability had disappeared almost entirely.

PMID- 29332754
TI  - Conservative management of thumb carpometacarpal osteoarthritis: An Italian
      survey of current clinical practice.
AB  - OBJECTIVE: The purpose of this study was to elucidate expert opinion on the
      conservative treatment of thumb carpometacarpal (CMC) joint osteoarthritis (OA).
      METHODS: A 21-item survey to determine the practice patterns of Italian hand
      therapists who treat arthritis of the CMC joint was developed and distributed
      through a professional online survey service to assure confidentiality and
      anonymity. RESULTS: Of the respondents, 80.8% were physical therapists; the
      remaining 19.2% were occupational therapists. 84.6% of the specialists who make
      decisions regarding patient pain management education. CONCLUSIONS: There is
      variability in the knowledge and practice patterns of Italian hand therapists
      relating to conservative management of thumb CMC OA.

PMID- 29332755
TI  - Investigating the anticipatory postural adjustment phase of gait initiation in
      different directions in chronic ankle instability patients.
AB  - OBJECTIVE: The main objective of the present study was to analyze how supra
      spinal motor control mechanisms are altered in different directions during
      anticipatory postural phase of gait initiation in chronic ankle instability
      patients. It seems that supra spinal pathways modulate anticipatory postural
      adjustment phase of gait initiation. Yet, there is a dearth of research on the
      effect of chronic ankle instability on the anticipatory postural adjustment phase
      of gait initiation in different directions. METHOD: A total of 20 chronic ankle
      instability participants and 20 healthy individuals initiated gait on a force
      plate in forward, 30 degrees  lateral, and 30 degrees  medial directions.
      RESULTS: According to the results of the present study, the peak lateral center
      of pressure shift decreased in forward direction compared to that in other
      directions in both groups. Also, it was found that the peak lateral center of
      pressure shift and the vertical center of mass velocity decreased significantly
      in chronic ankle instability patients, as compared with those of the healthy
      individuals. CONCLUSION: According to the results of the present study, it seems
      that chronic ankle instability patients modulate the anticipatory postural
      adjustment phase of gait initiation, compared with healthy control group, in
      order to maintain postural stability. These changes were observed in different
      directions, too.

PMID- 29332756
TI  - Asymmetry of activation of lateral abdominal muscles during the
      neurodevelopmental traction technique.
AB  - OBJECTIVE: The aim of the study was to evaluate the symmetry and pattern of
      activation of lateral abdominal muscles (LAM) in response to neurodevelopmental
      traction technique. DESIGN AND PARTICIPANTS: Measurements of LAM thickness were
      performed in four experimental conditions: during traction with the force of 5%
      body weight (5% traction): 1) in neutral position, 2) in 20 degrees  posterior
      trunk inclination; during traction with the force of 15% body weight (15%
      traction): 3) in neutral position, 4) in 20 degrees  posterior trunk inclination.
      Thirty-seven healthy children participated in the study. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: To evaluate LAM activation level ultrasound
      technology was employed (two Mindray DP660 devices (Mindray, Shenzhen, China)
      with 75L38EA linear probes). An experiment with repeated measurements of the
      dependent variables was conducted. RESULTS: Side-to-side LAM activation asymmetry
      showed relatively high magnitude, however, significant difference was found only
      in case of the obliquus externus (OE) during stronger traction (P < 0.05). The
      magnitude of LAM thickness change formed a gradient, with the most profound
      transversus abdominis (TrA) showing the smallest change, and the most superficial
      OE - the greatest. The inter-muscle differences were most pronounced between the
      OE and TrA (P < 0.001). CONCLUSIONS: During the neurodevelopmental traction
      technique there is a difference in individual LAM activation level, with deeper
      muscles showing less intense activation. In statistical terms, the only signs of
      side-to-side asymmetry of LAM activation are visible in case of the OE, however,
      the magnitude of asymmetry is relatively high. The results allow to identify
      patterns of activation of LAM in children showing typical development that will
      serve as a reference in future studies in children with neurological disorder.

PMID- 29332757
TI  - Activation of lower limb muscles with different types of mount in hippotherapy.
AB  - OBJECTIVES: To analyze muscle activation of lower limbs (LL) of subjects in
      hippotherapy sessions. METHODS: The study included 10 healthy subjects, five male
      and five female, with an average age of 24.03 (+/-4.06) years. Subjects underwent
      four hippotherapy sessions of 30 min with interval of one week, and each session
      was performed with a different type of mount material in the following order: 1st
      performed with saddle and feet in the stirrups (S1), 2nd with saddle and feet off
      the stirrups (S2), 3rd with blanket and feet off the stirrup (S3) and 4th with
      blanket and feet in the stirrups (S4). Surface electromyographies were performed
      at 1, 10, 20 and 30 min of session, and the electrodes were placed on muscle
      bellies bilaterally on the muscles rectus femoris, vastus medialis, vastus
      lateralis and tibialis anterior. RESULTS: The analysis of muscle activity during
      these four sessions showed a significant difference in muscle recruitment in LL,
      and sessions with blanket and feet in the stirrups provided greater muscle
      activation of quadriceps and tibialis anterior with the horse at step gait (p =
      0.0002). CONCLUSION: The results suggest that feet positioned in the stirrups is
      a relevant factor for greater muscle recruitment in LL to maintain postural
      balance while riding, especially using a blanket as mount material for ride a
      horse.

PMID- 29332758
TI  - Prevalence of physical activity among adolescents in southern Brazil.
AB  - OBJETIVE: The aim of this study was to estimate the prevalence of low physical
      activity levels and to identify related factors (sociodemographic, lifestyle and
      body weight status) in adolescents. METHODS: The study included 1103 students
      aged 14-19 years from city of Sao Jose/SC, Brazil. Physical activity was assessed
      using a questionnaire that classified adolescents into those who meet
      recommendations and those who do not meet recommendations. Independent variables
      were gender, age, monthly household income, maternal education, balanced diet,
      number of physical education classes, sleep/day, tobacco use, excessive alcohol
      use, screen time and weight status. Binary logistic regression was used to
      estimate odds ratios and 95% confidence intervals. RESULTS: Prevalence of
      inadequate levels of physical activity was 77.2%. Older students and those with
      lower monthly family income were more likely to have inadequate levels of
      physical activity. Female adolescents and older students were more likely to be
      sufficiently active compared to male and younger adolescents. Adolescents who
      sleep more hours/day were more likely to be insufficiently active. CONCLUSION:
      Efforts to increase levels of physical activity should be focused on older
      adolescents and those with lower monthly family income.

PMID- 29332759
TI  - Neck pain in Iranian school teachers: Prevalence and risk factors.
AB  - Neck pain (NP) is a common occupational health problem associated with a number
      of professions. Many studies indicate that NP is common among teachers, yet no
      published study was found to address the prevalence and risk factors of NP in
      Iranian school teachers. The purpose of the current study was to assess the
      prevalence and risk factors for NP among school teachers in Iran. A cross
      sectional study was conducted on 586 randomly selected primary and high schools
      teachers from 22 schools in Tehran, Iran. Point, last month, last 6 months,
      annual, and lifetime prevalence rates of NP were 24%, 29%, 33%, 37%, and 43%,
      respectively. There was a significant association and increased prevalence of NP
      with a number of risk factors such as; being female, age, general health, length
      of employment, regular exercise and job satisfaction (P < 0.05 in all instances).
      Therefore, some individual and occupational factors may make conditions relevant
      for the development of NP among teachers.

PMID- 29332760
TI  - Ischemic compression and kinesiotherapy on chronic myofascial pain in breast
      cancer survivors.
AB  - OBJECTIVE: assess the effects of ischemic compression and kinesiotherapy on the
      rehabilitation of breast cancer survivors with chronic myofascial pain. METHODS:
      A randomized, controlled, blinded clinical trial was performed with 20 breast
      cancer survivors with myofascial trigger point in the upper trapezius muscle.
      Patients were randomly allocated to ischemic compression + kinesiotherapy (G1, n
      = 10) and kinesiotherapy (G2, n = 10). Both groups were submitted to 10 sessions
      of treatment. The variables evaluated were: Numeric Rating Scale, Pain Related
      Self-Statement Scale, pressure pain threshold, Functional Assessment of Cancer
      Therapy-Breast and Infrared thermography. RESULTS: A significant reduction (p <
      0.05) was observed in pain intensity after 10 sessions in Groups 1 and 2, a
      significant increase (p < 0.05) in pressure pain threshold in both the operated
      and non-operated side after 10 sessions for Group 1. CONCLUSION: Ischemic
      compression associated with kinesiotherapy increases the pressure pain threshold
      on the myofascial trigger point in the upper trapezius muscle and reduces the
      intensity of pain in breast cancer survivors with myofascial pain.

PMID- 29332761
TI  - Exercise on balance and function for knee osteoarthritis: A randomized controlled
      trial.
AB  - OBJECTIVES: To assess balance and function of symptomatic and asymptomatic
      subjects with knee osteoarthritis (OA) and investigate the influence of physical
      exercise. DESIGN: Subjects were divided into three groups: Group 1 (n = 15),
      symptomatic knee OA; Group 2 (n = 11), asymptomatic knee OA; and Group 3 (n =
      16), knee OA and no intervention. History of falls, the WOMAC questionnaire,
      balance and functionality were assessed. RESULTS: After intervention, there was a
      significant difference in the total WOMAC score and in the pain and function
      domains only in Group 1. After intervention, Group 2 showed significant
      differences in decreased time on the Step Up/Over test and postural sway
      increased. CONCLUSION: After the intervention, the symptomatic group reported
      improvement in pain and function on the WOMAC, while the asymptomatic group
      showed improvement in performance in the Step Up/Over test. There were no new
      episodes of falls in groups 1 and 2.

PMID- 29332762
TI  - The effect of foot orthoses on joint moment asymmetry in male children with
      flexible flat feet.
AB  - INTRODUCTION: It has been widely postulated that structural and functional
      misalignments of the foot, such as flat foot, may cause mechanical deviations of
      the lower limb during walking. The aim of this study was to investigate the
      effect of foot orthoses on lower extremity joint moment asymmetry during the
      stance phase of walking in children with asymptomatic flexible flat feet.
      METHODS: Fourteen volunteer male children, clinically diagnosed with flexible
      flat feet, participated in this study. Subjects completed 12 walking trials at a
      self-selected walking speed while 3-dimensional kinematic and kinetic data were
      collected for two conditions: shod with no orthoses, and shod with orthoses. The
      gait asymmetry index for each variable for each subject was defined as: (1
      (lesser moment/greater moment)) * 100. RESULTS: Results reveal no significant
      differences in ankle or knee joint moment asymmetry. However, the use of foot
      orthoses decreased asymmetry for the hip abduction moment (P = 0.04) compared to
      walking without orthoses and also resulted in subtle, non-significant increases
      in frontal plane subtalar and sagittal plane knee and hip joints moment
      asymmetry. CONCLUSION: We conclude that foot orthoses decrease frontal plane hip
      joint moment asymmetry, but have little effect on ankle and knee joint asymmetry.

PMID- 29332763
TI  - Fascia - The unsung hero of spine biomechanics.

PMID- 29332764
TI  - Pelvic musculoskeletal dysfunctions in women with and without chronic pelvic
      pain.
AB  - AIM: This study aimed to compare the prevalence of pelvic musculoskeletal
      dysfunctions in women with and without Chronic Pelvic Pain (CPP). MATERIALS
      &METHODS: A total of 84 women with and without CPP (42 in each group),
      participated in this cross-sectional analytical study. After collecting
      demographic information, clinical examinations were carried out to compare pelvic
      musculoskeletal dysfunctions between two groups. Kolmogorov-Smirnov (K-S)
      goodness-of-fit, Independent t, X2 and Pearson correlation tests were used for
      data analysis. Values of p < 0.05 were considered statistically significant.
      FINDINGS: Significant differences were found in the asymmetric iliac crest and
      pubic symphysis height (45.2% vs 9.5%), positive sacroiliac provocation and
      positive Carnett's tests (50% vs 4.8%), (p < 0.05). CPP Patients exhibited more
      tenderness at Levator ani, Piriformis, and Obturator Internus muscles, also
      higher degrees of pelvic inclination (p < 0.05). CONCLUSION: Higher frequency of
      pelvic musculoskeletal dysfunctions in women with CPP suggests the value of
      routine musculoskeletal examinations for earlier diagnosis of musculoskeletal
      originated CPP and effective management of these patients.

PMID- 29332765
TI  - Aquatic myofascial release applied after high intensity exercise increases
      flexibility and decreases pain.
AB  - OBJECTIVES: To investigate aquatic myofascial release (AMR) effects on
      flexibility and delayed onset muscle soreness, after high intensity exercises.
      STUDY DESIGN: 15 participants, control (CON) and intervention (INT), 3 moments,
      pre (Pre), after (Post) and 50 min after (Post 50/Post AMR). 6 exercises, 5 sets,
      15 reps at 85% of 1 maximum repetition, followed, or not, by 50 min of AMR.
      VARIABLES: Heart rate, lactate, rate of perceived exertion, pain and flexibility.
      RESULTS: Pain perception decreased in all moments (CON4.47 +/- 2.36; INT1.13 +/-
      1.46, p = 0.0002). Flexibility only increased for the fingertip to floor test in
      both phases in the Post50/Post AMR compared to Post (CON14.33 +/- 9.19Pre, 15.07
      +/- 9.37Post (p = 0.7) and 12.8 +/- 4.69Post50 (p = 0.4); INT14.53 +/- 9.06Pre,
      13.87 +/- 9.88Post (p = 0.2) and 11.03 +/- 8.96Post AMR (p = 0.001)). The Well's
      bench improved only for the Post AMR compared to Pre in the INT phase (INT24.79
      +/- 9.91Pre; 27.67 +/- 9.46Post AMR p = 0.0000023). CONCLUSION: We concluded that
      AMR is effective to reduce pain perception and to improve flexibility of the
      studied population submitted to a high intense exercise session.

PMID- 29332766
TI  - Cognitive function in Rett syndrome: Profoundly impaired or near normal?

PMID- 29332768
TI  - Will a Screwdriver Work?

PMID- 29332767
TI  - Burn Care: Resuscitation and Respiratory Care.

PMID- 29332769
TI  - Articles That May Change Your Practice: Hypertonic Fluid Resuscitation in Trauma.

PMID- 29332770
TI  - Forum.

PMID- 29332771
TI  - 26th Critical Care Transport Medicine Conference.

PMID- 29332772
TI  - 2017 Community Awards.

PMID- 29332773
TI  - Does Medical Staffing Influence Perceived Safety? An International Survey on
      Medical Crew Models in Helicopter Emergency Medical Services.
AB  - OBJECTIVE: The competence, composition, and number of crewmembers have generally
      been considered to influence the degree of patient care and safety in helicopter
      emergency medical services (HEMS), but evidence to support the advantages of one
      crew concept over another is ambiguous; additionally, the benefit of physicians
      as crewmembers is still highly debated. METHODS: To compare perceived safety in
      different medical crew models, we surveyed international HEMS medical directors
      regarding the types of crew compositions their system currently used and their
      supportive rationales and to evaluate patient and flight safety within their
      services. RESULTS: Perceived patient and flight safety is higher when HEMS is
      staffed with a dual medical crew in the cabin. Tradition and scientific evidence
      are the most common reasons for the choice of medical crew. Most respondents
      would rather retain their current crew configuration, but some would prefer to
      add a physician or supplement the physician with an assistant in the cabin.
      CONCLUSION: Our survey shows a wide variety of medical staffing models in HEMS
      and indicates that these differences are mainly related to medical competencies
      and the availability of an assistant in the medical cabin. The responses suggest
      that differences in medical staffing influence perceived flight and patient
      safety.

PMID- 29332775
TI  - Development and Testing of a Neonatal Intubation Checklist for an Air Medical
      Transport Team.
AB  - OBJECTIVE: We developed a Neonatal Intubation Checklist for Airlift Northwest.
      Our goal was to improve the preparation, technical proficiency, and safety of
      neonatal intubation without increasing the time required to perform the
      procedure. METHODS: The Neonatal Intubation Checklist, a "call and response"
      checklist for neonatal intubation, was developed. Its effectiveness was evaluated
      during a baseline assessment and 2 practice sessions after a checklist
      orientation. Intubation proficiency was evaluated using a validated assessment
      tool that included a proficiency score, a global rating scale (GRS) score, and
      time to perform the procedure. RESULTS: Significant improvements in intubation
      proficiency and time to intubation were noted when teams used the intubation
      checklist (proficiency score: 29 [7] at baseline vs. 57 [1] with checklist, P <
      .001; GRS 2 [2, 2.5] at baseline vs. 5 [3, 5] with checklist, P < .001; baseline
      intubation time 626 [93] seconds vs. 479 (44) seconds with checklist, P < .001).
      These changes were associated with a large effect on proficiency (n2 = 0.89), GRS
      (n2 = 0.6), and time to successful intubation (n2 = 0.52). CONCLUSION: The use of
      the Neonatal Intubation Checklist improved transport team performance during
      simulated neonatal intubations and decreased the time required to successfully
      perform the procedure.

PMID- 29332774
TI  - An Analysis of Intoxicated Patients Transported by a Doctor Helicopter.
AB  - OBJECTIVE: We retrospectively investigated all of the intoxicated patients who
      were transported by a doctor helicopter (DH) in eastern Shizuoka between April
      2004 and December 2015 to determine when air medical transport was used in cases
      of toxic exposure. METHODS: Subjects were divided into 2 groups: an outpatient
      group of subjects who went home after receiving a medical evaluation and
      treatment and an admission group. RESULTS: The outpatient and admission groups
      included 17 and 31 subjects, respectively. The ratio of dispatching the DH to the
      scene and the median Glasgow Coma Scale score in the outpatient group were
      greater, and the shock index in the outpatient group was significantly smaller
      than in the admission group. The duration from exposure of intoxicated agents to
      contact by staffs of the DH in the outpatient group was also smaller than in the
      admission group. CONCLUSION: The level of consciousness and shock index may be
      important factors dictating whether or not to dispatch the DH in order to prevent
      secondary damage induced by unstable circulation.

PMID- 29332776
TI  - Compliance With a National Standard by Norwegian Helicopter Emergency Physicians.
AB  - OBJECTIVE: The "National Standard Requirements for Helicopter Emergency Medicine
      Services Physicians" gives recommendations on medical requirements for flight
      physicians. This study describes the level of formal competence, experience, and
      guideline compliance of Norwegian helicopter emergency medical service (HEMS)
      physicians. METHODS: In May 2013, all HEMS physicians with full-time engagement
      at Norwegian HEMS bases were invited to participate in a cross-sectional survey
      using a structured, Web-based questionnaire. RESULTS: A total of 108 (79%) of 136
      physicians replied to the survey, and all bases were represented. The majority
      (89%) had specialist training, and more than 60% had longer than 6 years of
      experience as a flight physician. Over 60% had attended trauma, pediatric, and
      incubator courses, and all physicians worked regularly in an anesthesia
      department. Most physicians were participating in simulation and procedure
      training. CONCLUSION: Many of the basic requirements of the guidelines were met
      by HEMS physicians, but room exists for improvements. Norwegian HEMS physicians
      are experienced, but a need exists for a more structured curriculum in emergency
      medicine for HEMS physicians based on the broad spectrum of presented medical
      conditions to ensure optimal quality of care and safety for all patients in
      Norway.

PMID- 29332777
TI  - Means for Transport in Patients After Remote Extracorporeal Membrane Oxygenation
      Implantation.

PMID- 29332778
TI  - Cricothyrotomy in Helicopter Emergency Medical Service Transport.
AB  - OBJECTIVE: Airway management is a requisite skill set for helicopter emergency
      medical service (HEMS) providers. Cricothyrotomy is a potentially lifesaving
      skill that is used when other airway maneuvers fail. The authors reviewed all
      transports by a helicopter program in which cricothyrotomy was performed to
      assess the frequency, success, and technique. METHODS: This was a retrospective
      chart review of air medical patient records from an electronic medical record
      system over a 112-month period. RESULTS: During the study period, 22,434 patients
      were transported, 13 (.057%) of whom underwent cricothyrotomy. The typical
      patient was a male trauma victim with a mean Glasgow Coma Score of 5 transported
      from an accident scene with a mean age of 34.3 years. Six (46%) of the patients
      were alive at 24 hours. All patients (13/100%) received attempted endotracheal
      intubation; the mean number of attempts per patient was 2. The success rate was
      100% with all patients ventilated via cricothyrotomy. CONCLUSION: This study
      shows cricothyrotomy is a rarely performed skill but that HEMS providers are able
      to successfully learn the skill with proper training and oversight.

PMID- 29332779
TI  - Helicopter Emergency Medical Services Literature 2014 to 2016: Lessons and
      Perspectives, Part 1-Helicopter Transport for Trauma.

PMID- 29332780
TI  - Social Media and Integrity.

PMID- 29332781
TI  - Pediatric Extracorporeal Cardiopulmonary Resuscitation Patient With Traumatic
      Subarachnoid Hemorrhage and Takotsubo Syndrome.
AB  - Takotsubo syndrome is rare in pediatric patients but must be considered in
      patients with subarachnoid hemorrhage with pulmonary edema and cardiomyopathy. A
      systematic, collaborative approach is needed to facilitate emergent transfer of
      patients where extracorporeal cardiopulmonary resuscitation (e-CPR) is used as a
      lifesaving measure. Extracorporeal membrane oxygenation (ECMO) use in transport
      requires preplanning, role delineation, resources, and research efforts to be
      successful. We present an unusual transport case of successful e-CPR/ECMO
      treatment of Takotsubo syndrome in a 12-year-old boy with an isolated traumatic
      intracranial injury, cardiomyopathy with pulmonary edema, and multiple cardiac
      arrests.

PMID- 29332782
TI  - Long-Distance, Nonstop Neonatal Transport From Shanghai, China, to Genoa, Italy.
AB  - The purpose of this article is to describe the long-distance, nonstop
      intercontinental transport of a severely ill, mechanically ventilated newborn
      from Shanghai, China, to Genoa, Italy focusing in particular on the clinical and
      planning difficulties. The aircraft equipment, the assessment and preparation for
      transport are discussed.

PMID- 29332783
TI  - Out-of-Hospital Lateral Canthotomy and Cantholysis: A Case Series and Screening
      Tool for Identification of Orbital Compartment Syndrome.

PMID- 29332784
TI  - Air Transport of a Patient With Impending Cerebral Herniation From Tension
      Pneumocephalus.
AB  - Tension pneumocephalus is a rare but dangerous complication of craniotomy, sinus
      surgery, and traumatic cranial injury. Compared with simple pneumocephalus, which
      often resolves spontaneously over the course of a few days, tension
      pneumocephalus tends to increase with ongoing cerebrospinal fluid leak and
      requires immediate neurosurgical treatment to prevent cerebral herniation. Air
      transport of patients with tension pneumocephalus for neurosurgical care entails
      a risk of neurologic worsening because of changes in ambient air pressure with
      altitude and cabin pressurization. We describe a case in which severe symptomatic
      tension pneumocephalus developed after endoscopic endonasal sinus surgery in an
      81-year-old man. The patient lived in a remote area and required air transport
      for medical care. Pretreatment with oxygen therapy and maintaining the patient in
      a flat supine position rapidly improved his neurologic status, allowing
      transportation without incidence. A recommendation was also made to the medical
      transport team to fly at the lowest possible altitude. Specific precautions may
      enable safe transport of these critically ill patients for treatment, although
      further data must be obtained before these can be definitively recommended.

PMID- 29332785
TI  - The "Squeeze," an Interesting Case of Mask Barotrauma.

PMID- 29332786
TI  - Recent advances and developments on integrating nanotechnology with
      chemiluminescence assays.
AB  - Chemiluminescence (CL) techniques are extensively utilized for detection of
      analytes due to their high sensitivity, rapidity and selectivity. With the advent
      of nanotechnology and incorporation of the nanoparticles in the CL system has
      revolutionized the assays due to their unique optical and mechanical properties.
      Several CL-based reactions have been developed where these nanoparticle based CL
      sensors have evolved as excellent prospects for sensing in various analytical
      applications. This review article addresses the nanoparticles based CL detection
      system that are recently developed, the mechanisms has been summarized and the
      role of luminophors have been discussed. This article critically analyzes the
      optimal conditions for the CL detection along with quantitative assessment of the
      analytes. We have included the use of semiconductor nanoparticles, metal
      nanoparticles, graphene based nanostructures, mesoporous nanospheres, layered
      double hydroxides, clays for CL detection. The scope and application of these
      nanoscale material based CL system in various branches of science and technology
      including chemistry, biomedical applications, pharmaceutics, food, environmental
      and toxicological applications has been critically summarized.

PMID- 29332787
TI  - Rapid and interference-free analysis of nine B-group vitamins in energy drinks
      using trilinear component modeling of liquid chromatography-mass spectrometry
      data.
AB  - The aim of the present work was to develop a rapid and interference-free method
      based on liquid chromatography-mass spectrometry (LC-MS) for the simultaneous
      determination of nine B-group vitamins in various energy drinks. A smart and
      green strategy that modeled the three-way data array of LC-MS with second-order
      calibration methods based on alternating trilinear decomposition (ATLD) and
      alternating penalty trilinear decomposition (APTLD) algorithms was developed. By
      virtue of "mathematical separation" and "second-order advantage", the proposed
      strategy successfully solved the co-eluted peaks and unknown interferents in LC
      MS analysis with the elution time less than 4.5min and simple sample preparation.
      Satisfactory quantitative results were obtained by the ATLD-LC-MS and APTLD-LC-MS
      methods for the spiked recovery assays, with the average spiked recoveries
      ranging from 87.2-113.9% to 92.0-111.7%, respectively. These results acquired
      from the proposed methods were confirmed by the LC-MS/MS method, which shows a
      quite good consistency with each other. All these results demonstrated that the
      developed chemometrics-assisted LC-MS strategy had advantages of being rapid,
      green, accurate and low-cost, and it could be an attractive alternative for the
      determination of multiple vitamins in complex food matrices, which required no
      laborious sample preparation, tedious condition optimization or more
      sophisticated instrumentations.

PMID- 29332788
TI  - Turn-on fluorescent sensor for the detection of glucose using manganese dioxide
      phenol formaldehyde resin nanocomposite.
AB  - Monitoring blood glucose has attracted considerable attention because diabetes
      mellitus is a global public health problem. Herein, we reported a turn-on
      fluorescence detection strategy based on manganese dioxide (MnO2)-phenol
      formaldehyde resin (PFR) nanocomposite for rapid, sensitive, and selective
      detection of glucose levels in human blood. In this biosensing system, MnO2
      nanoshell on the PFR nanoparticle surfaces serve as a quencher. PFR fluorescence
      can make a recovery in the presence of H2O2, reducing MnO2 to Mn2+. The sensor
      shows a linear range from 50nM to 90MUM with a low detection limit of 20nM for
      H2O2 detection. Thus, the glucose can be detected on the basis of the enzymatic
      conversion of glucose by glucose oxidase to produce H2O2. This method exhibits a
      wide linear range from 5MUM to 1mM with a low detection limit of 1.5MUM. Because
      of the excellent photostability offered by PFR, the developed strategy has been
      successfully applied for the diagnosis of diabetes mellitus in human blood
      samples. Compared with commercial glucometer, our method showed satisfactory
      results, indicating the significant reliability. The developed turn-on
      fluorescent sensor might hold great promise in nanomedicine and bioanalysis.

PMID- 29332789
TI  - Mn2+-doped NaYF4:Yb,Er upconversion nanoparticles for detection of uric acid
      based on the Fenton reaction.
AB  - A novel fluorescence method for the determination of hydrogen peroxide (H2O2) and
      uric acid (UA) was developed. The procedure was based on the hydroxyl radicals
      (.OH), which effectively quenched the fluorescence of the Mn2+-doped NaYF4:Yb,Er
      upconversion nanoparticles (UCNPs). Based on the property of Mn2+-doped
      NaYF4:Yb,Er upconversion nanoparticles, the Fenton reaction and enzymatic
      reaction of uric acid, this method could be used for highly sensitive detection
      of H2O2 and uric acid. Under optimal conditions, we observed that the
      fluorescence quenching signal showed good linearity with the H2O2 concentration
      in the range of 3.00*10-8 M ~ 6.00*10-5 M, and the detection limit of this assay
      was 1.30*10-8 M. Meanwhile, the linear concentration range for UA was 4.00*10-9 M
      ~ 1.00*10-5 M, and the lower limit of detection was 1.90*10-9 M. Furthermore, the
      developed method was successfully used for the determination of UA levels in
      human serum with satisfactory results.

PMID- 29332790
TI  - Ultrasensitive electrochemical detection of poly (ADP-ribose) polymerase-1 via
      polyaniline deposition.
AB  - Recent findings have thrust poly ADP (ADP: adenosine diphosphate)-ribose
      polymerase-1 (PARP-1) into the limelight as potential chemotherapeutic target
      because it is closely related to the development of tumor. So, studies on its
      detection and inhibitors evaluation have attracted more attention. It is
      interesting that poly (ADP-ribose) (PAR), the catalytic product of PARP-1 in the
      existence of nicotinamide adenine dinucleotide (NAD+), possess twice charge
      density of DNA strands. PAR contain 200 units, i.e., about 400bp bases, and
      multiple branched strands. So, plentiful negative charges on PAR supplied
      exquisite environment for PANI deposition, which was triggered by horseradish
      peroxidase (HRP). Because of the unique electrochemical property of PANI,
      ultrasensitive electrochemical detection of PARP-1 was proposed. Under optimum
      conditions, DPV intensity linearly increased with the increment of PARP-1 in the
      range of 0.005-1.0 U. The detection limit was 0.002 U, which was comparable or
      more sensitive than that obtained from previously reported strategies.

PMID- 29332791
TI  - Highly sensitive and reproducible non-enzymatic glucose sensor fabricated by drop
      casting novel nanocomposite with 3D architecture and tailorable properties
      prepared in controllable way.
AB  - Novel nanocomposite has tailorable properties and ordered 3D architecture similar
      to the structure of materials prepared by electrodeposition which is convenient
      and efficient but the reproducibility is limited because of the uncontrollable
      preparation process, was scientifically synthetized in controllable way and used
      for non-enzymatic glucose sensor for the first time. Flower-like alpha-Ni(OH)2
      with high specific surface areas and good anion transport ability benefited from
      its distinctive stacking faults and turbostratic disorder structure was
      synthesized through facile one-step hydrothermal method. Oversaturated gold
      nanoparticles (AuNPs) have been innovatively decorated on flower-like alpha
      Ni(OH)2 to improve the electrical conductivity, in turn, AuNPs would possess the
      higher catalytic activity when supported on Ni(OH)2, so the resultant AuNPs
      decorated alpha-Ni(OH)2 (AuNPs@alpha-Ni(OH)2) also has excellent synergistic
      catalytic effect and improved selectivity. On this basis, beta-cyclodextrins
      functionalized reduced graphene oxide (beta-rGO) with enhanced dispersivity was
      scientifically added at optimized proportion to reduce the interparticle
      resistance of AuNPs@alpha-Ni(OH)2 as 2D electron transport channels, and to
      improve film-forming ability of the obtained nanocomposite via forming stable 3D
      network structure. Non-enzymatic glucose sensor fabricated through drop-casting
      the prepared nanocomposite on glass carbon electrode has high sensitivity up to
      559.314MUAmM-1cm-2 over the low concentration range and 327.199MUAmM-1cm-2 over
      the higher concentration range, comparable to the sensors modified by
      electrodeposition method, indicating that prepared nanocomposite with controlling
      nanoscale composition and architectures based on rational design is an effective
      strategy to construct electrochemical sensor with excellent performance.

PMID- 29332792
TI  - Silver ions enhanced AuNCs fluorescence as a turn-off nanoprobe for
      ultrasensitive detection of iodide.
AB  - Fluorescence nanoprobes are frequently employed to construct sensitive biosensors
      via turn-on and turn-off strategy. In this paper, a novel strategy for
      ultrasensitive detection of iodide was firstly constructed based on Ag+ regulated
      photoluminescence enhancement of gold nanoclusters (AuNCs) as a turn-off
      nanoplatform. In the presence of Ag+, the fluorescence (FL) intensity of AuNCs
      can be enhanced obviously. When adding iodide ions (I-) in the Ag+-AuNCs, Ag+ can
      be pulled down from AuNCs and results in quenching of the fluorescent effectively
      owing to the combination between Ag+ and I-. Compared with that of I- directly
      reaction with AuNCs, the introducing of Ag+ shows improved quenching efficiency
      from 32% to 66% since I- can react with Ag+ as well as AuNCs. Therefore, the
      platform could be applied to assay Ag+ and I-, on the basis of the FL enhancement
      and the further FL quenching. The detection ranges and detection limits were 0.2
      12MUM and 0.06MUM for Ag+, 0.001-6MUM and 0.3nM for I-, respectively. The new
      sensing method based on ion regulation to enhance the detection sensitivity can
      extend to the appliance of other fluorescent materials in biosensing and
      biomedical field.

PMID- 29332793
TI  - Label-free detection of histone based on cationic conjugated polymer-mediated
      fluorescence resonance energy transfer.
AB  - A simple and homogeneous histone assay is developed based on histone-induced DNA
      compressing coupled with cationic conjugated polymer (CCP)-mediated fluorescence
      resonance energy transfer (FRET). In this strategy, the CCP serves as the FRET
      donor and SYBR Green I (SG), which can strongly fluoresce not at its free state
      but after intercalated into the double stranded calf thymus DNA (dsDNA), serves
      as the acceptor of FRET. In the absence of histone, the dsDNA-SG and CCP combine
      with each other through electrostatic interaction and the strong FRET from CCP to
      SG occurs due to the overlapping between the fluorescent emitting spectrum of the
      CCP and the absorption spectrum of SG. Upon the introduction of histone, the
      formed compact complex of histone/dsDNA will lead to the compression of dsDNA
      structure and prevent SG binding to dsDNA and fluorescing, which gives rise to a
      significant decrease of FRET efficiency between CCP and SG. Thus, the
      quantitative analysis of histone is realized by monitoring the change of FRET
      ratio, namely, the intensity ratio of the two emission bands of CCP and SG. Due
      to the light harvesting and fluorescence amplification properties of CCP, high
      sensitivity is achieved with a low detection limit of 0.74ng/mL histone. This
      strategy provides a simple, homogeneous and sensitive strategy for histone
      analysis in the study of histone-related biological processes.

PMID- 29332794
TI  - A sensitive SPR biosensor based on hollow gold nanospheres and improved sandwich
      assay with PDA-Ag@Fe3O4/rGO.
AB  - A novel surface plasmon resonance (SPR) biosensor based on hollow gold
      nanospheres (HGNPs) and an improved sandwich assay was developed to detect rabbit
      IgG. The electromagnetic coupling between the HGNPs and Au film, and the notable
      plasmonic fields spread over the inner and outer surfaces of HGNPs, led to the
      considerable amplification of the SPR signal. Polydopamine-Ag@Fe3O4/reduced
      graphene oxide (PDA-Ag@Fe3O4/rGO) was introduced to bind detection antibody (Ab2)
      to form the improved sandwich structure. Ag nanoparticles were excited to produce
      SPR and their hot electrons were doped on graphene thin films, which amplified
      the response of biomolecules. Magnetic nanoparticles (Fe3O4) simplified the
      collection of Ab2-PDA-Ag@Fe3O4/rGO. An external layer of polydopamine (PDA)
      permitted the efficient immobilization of Ab2 without activation via abundant
      functional groups and protected the nanoparticles from etching or agglomeration.
      In addition, because of its large mass, Ab2-PDA-Ag@Fe3O4/rGO also played a key
      role in the further amplification of the SPR response signals. This novel SPR
      biosensor exhibited an effective response to the rabbit IgG at the different
      concentrations ranging from 0.019 to 40.00MUgmL-1. This value is 132 times lower
      than that observed for a traditional SPR biosensor based on Au-3
      mercaptopropionic acid and 8 times lower than that obtained from an Ab2 sandwich
      assay, which indicates that the SPR sensor has high sensitivity. In addition, the
      designed biosensor showed satisfactory recoveries to detect the rabbit IgG spiked
      in serum samples. Therefore, the novel SPR biosensor with high sensitivity and
      acceptable recovery has potential for practical applications.

PMID- 29332795
TI  - Polymer-based materials modified with magnetite nanoparticles for enrichment of
      phospholipids.
AB  - A polymeric material modified with magnetic nanoparticles (MNPs) has been
      synthesized and evaluated as sorbent both for solid-phase extraction (SPE) and
      dispersive magnetic solid-phase extraction (MSPE) of phospholipids (PLs) in human
      milk samples. The synthesized sorbent was characterized by scanning electron
      microscopy and its iron content was also determined. Several experimental
      variables that affect the extraction performance (e.g. loading solvent,
      breakthrough volume and loading capacity) were investigated and a comparison
      between conventional SPE and MSPE modalities was done. The proposed method was
      satisfactorily applied to the analysis of PLs in human milk fat extracts in
      different lactation stages and the extracted PLs were determined by means of
      hydrophilic interaction liquid chromatography using evaporative light scattering
      detection.

PMID- 29332796
TI  - Direct olive oil analysis by mass spectrometry: A comparison of different ambient
      ionization methods.
AB  - Analytical methods based on ambient ionization mass spectrometry (AIMS) combine
      the classic outstanding performance of mass spectrometry in terms of sensitivity
      and selectivity along with convenient features related to the lack of sample
      workup required. In this work, the performance of different mass spectrometry
      based methods has been assessed for the direct analyses of virgin olive oil for
      quality purposes. Two sets of experiments have been setup: (1) direct analysis of
      untreated olive oil using AIMS methods such as Low-Temperature Plasma Mass
      Spectrometry (LTP-MS) or paper spray mass spectrometry (PS-MS); or alternatively
      (2) the use of atmospheric pressure ionization (API) mass spectrometry by direct
      infusion of a diluted sample through either atmospheric pressure chemical
      ionization (APCI) or electrospray (ESI) ionization sources. The second strategy
      involved a minimum sample work-up consisting of a simple olive oil dilution (from
      1:10 to 1:1000) with appropriate solvents, which originated critical carry over
      effects in ESI, making unreliable its use in routine; thus, ESI required the use
      of a liquid-liquid extraction to shift the measurement towards a specific part of
      the composition of the edible oil (i.e. polyphenol rich fraction or lipid/fatty
      acid profile). On the other hand, LTP-MS enabled direct undiluted mass analysis
      of olive oil. The use of PS-MS provided additional advantages such as an extended
      ionization coverage/molecular weight range (compared to LTP-MS) and the
      possibility to increase the ionization efficiency towards nonpolar compounds such
      as squalene through the formation of Ag+ adducts with carbon-carbon double
      bounds, an attractive feature to discriminate between oils with different degree
      of unsaturation.

PMID- 29332797
TI  - Electrodialytic in-line preconcentration for ionic solute analysis.
AB  - Preconcentration is an effective way to improve analytical sensitivity. Many
      types of methods are used for enrichment of ionic solute analytes. However,
      current methods are batchwise and include procedures such as trapping and
      elution. In this manuscript, we propose in-line electrodialytic enrichment of
      ionic solutes. The method can enrich ionic solutes within seconds by quantitative
      transfer of analytes from the sample solution to the acceptor solution under an
      electric field. Because of quantitative ion transfer, the enrichment factor (the
      ratio of the concentration in the sample and to that in the obtained acceptor
      solution) only depends on the flow rate ratio of the sample solution to the
      acceptor solution. The ratios of the concentrations and flow rates are equal for
      ratios up to 70, 20, and 70 for the tested ionic solutes of inorganic cations,
      inorganic anions, and heavy metal ions, respectively. The sensitivity of ionic
      solute determinations is also improved based on the enrichment factor. The method
      can also simultaneously achieve matrix isolation and enrichment. The method was
      successively applied to determine the concentrations of trace amounts of
      chloroacetic acids in tap water. The regulated concentration levels cannot be
      determined by conventional high-performance liquid chromatography with
      ultraviolet detection (HPLC-UV) without enrichment. However, enrichment with the
      present method is effective for determination of tap water quality by improving
      the limits of detection of HPLC-UV. The standard addition test with real tap
      water samples shows good recoveries (94.9-109.6%).

PMID- 29332798
TI  - Supported carbon dots serve as high-performance adsorbent for the retention of
      trace cadmium.
AB  - Carbon dots were prepared via a one-pot hydrothermal route, and a new solid-phase
      extraction (SPE) adsorbent was developed by immobilizing the carbon dots on the
      microcarrier cytopore, shortly termed as C-dots@cytopore. The C-dots@cytopore
      composites were characterized by means of FT-IR, SEM, XPS and fluorescence
      spectrometry. The performance of the composites for the adsorption of heavy
      metals was thoroughly evaluated by using cadmium as a model. The binding of
      cadmium on C-dots@cytopore fits Langmuir adsorption, and the adsorption dynamic
      follows pseudo-second-order adsorption kinetics model. The binding of cadmium was
      pH-dependent, with a maximum adsorption capacity of 2420MUgg-1 obtained at pH 4
      7. A novel separation and preconcentration procedure was thus developed for trace
      cadmium using the C-dots@cytopore composites as SPE sorbent. The retained cadmium
      could be readily eluted and recovered by a 0.1molL-1 HNO3 solution and further
      quantified with graphite furnace atomic absorption spectrometry (GFAAS). With a
      sample volume of 1.0mL, an enrichment factor of 17.85 was obtained with a
      detection limit of 1.8ngL-1 and a RSD value of 2.6% at 0.1MUgL-1 (n = 9). The
      procedure was further validated by analyzing cadmium in certified reference
      materials and a series of environmental water samples.

PMID- 29332800
TI  - Acidity of substituted cathinones studied by capillary electrophoresis using the
      standard and fast alternative approaches.
AB  - Cathinone derivatives are notorious but still weakly characterized molecules,
      known mainly as components of the designer and illicit drugs. The knowledge on
      their acidity is scarce and incomplete, therefore, we decided to determine the
      pKa values for six of them: 2-methylmethcathinone, 3-methylmethcathinone, 4
      methylmethcathinone, alpha-pyrrolidinovalerophenone, methylenedioxypyrovalerone
      and ephedrone. For that purpose we employed capillary electrophoresis, which is
      known for its accurateness in comparison to other analytical techniques. We used
      and compared two methodologically different approaches. The standard method
      relied on measuring electrophoretic mobility across the broad pH range and
      fitting the sigmoidal function. The obtained pKa values were in the range 8.59
      9.10, thus these molecules remain mostly protonated and positively ionized in the
      physiological conditions. The alternative two-values (TVM) and one-value methods
      (OVM), proposed by us previously, have been used herein for the first time to the
      cationic molecules. TVM enables estimation of pKa using only two electrophoretic
      mobility values, referring to the total and partial ionization. OVM requires only
      a single measurement because mobility of ion is predicted theoretically. Both TVM
      and OVM yielded only a small deviation of pKa from the standard approach,
      averagely 0.07-0.09pH unit. Two important issues have also been addressed: the
      potential of a maximally fast calculation method using no repetition at the given
      pH, and the accuracy of method with regard to pH attributed to partial
      ionization. As a whole, the analytical potential of the TVM/OVM approach seems to
      be huge and invaluable for fast pKa screening/estimation.

PMID- 29332799
TI  - Rapid identification of regulated organic chemical compounds in toys using
      ambient ionization and a miniature mass spectrometry system.
AB  - Rapid, on-site analysis was achieved through significantly simplified operation
      procedures for a wide variety of toy samples (crayon, temporary tattoo sticker,
      finger paint, modeling clay, and bubble solution) using a miniature mass
      spectrometry system with ambient ionization capability. The labor-intensive
      analytical protocols involving sample workup and chemical separation,
      traditionally required for MS-based analysis, were replaced by direct sampling
      analysis using ambient ionization methods. A Mini beta ion trap miniature mass
      spectrometer was coupled with versatile ambient ionization methods, e.g. paper
      spray, extraction spray and slug-flow microextraction nanoESI for direct
      identification of prohibited colorants, carcinogenic primary aromatic amines,
      allergenic fragrances, preservatives and plasticizers from raw toy samples. The
      use of paper substrates coated with Co3O4 nanoparticles allowed a great increase
      in sensitivity for paper spray. Limits of detection as low as 5MUgkg-1 were
      obtained for target analytes. The methods being developed based on the
      integration of ambient ionization with miniature mass spectrometer represent
      alternatives to current in-lab MS analysis operation, and would enable fast,
      outside-the-lab screening of toy products to ensure children's safety and health.

PMID- 29332801
TI  - A highly selective, colorimetric and ratiometric fluorescent probe for NH2NH2 and
      its bioimaging.
AB  - In this work, we report a novel approach which employed substrate-triggered
      intramolecular addition-cyclization cascade to develop a highly selective
      fluorescent probe E)-3-(4-(1H-phenanthro[9,10-d]imidazol-2-yl)phenyl)-1-(2
      hydroxylphenyl) prop-2-en-1-one (P-OH) for NH2NH2. The new sensing mechanism of P
      OH for NH2NH2 was investigated in detail by fluorescence spectroscopy, 1H NMR
      titration, mass spectrometry and control experiments. The synthesized probe
      showed ratiometric fluorescent response to NH2NH2 with naked-eye color changes
      from yellow to colorless. It's noteworthy that this probe displayed high
      sensitivity and selectivity to NH2NH2 over other species, including primary
      amines, Cys, Hcy, GSH, HS- and HSO3-. Furthermore, the probe can not only detect
      NH2NH2 in real water samples but also image NH2NH2 in living cells, indicating
      its potential utility for NH2NH2 sensing in environmental and biological samples.

PMID- 29332802
TI  - Total alpha1-acid glycoprotein determination in serum samples using disposable
      screen-printed electrodes and osmium (VI) as electrochemical tag.
AB  - Alpha-1-acid glycoprotein (AGP) or Orosomucoid is a serum glycoprotein which
      belongs to the group of acute phase proteins. It is a potential biomarker for
      inflammatory bowel diseases. In this sense, there is a need for developing fast
      and cheap analytical methods for diagnosis, prognosis and follow-up of these
      diseases. In this work, we propose a simple and cheap electrochemical method for
      total AGP determination using disposable carbon screen-printed electrodes (SPE)
      and using a selective acidic precipitation of the rest of proteins. This method
      avoids the use of biological components, decreasing dramatically the analysis
      cost. Firstly, AGP is labeled with an electrochemical tag (osmium (VI) complex)
      and then the total amount of AGP is quantified by adsorptive transfer stripping
      square wave voltammetry. The method optimized showed a good linear correlation (r
      = 0.9992) and limit of detection of 1.6mgl-1. The methodology was successfully
      applied to quantify AGP in a commercial serum sample. This methodology could be
      useful in clinical diagnosis because of AGP levels increase two or three times
      when inflammatory processes happen. Moreover, the inherent advantages of SPE
      technology (low sample consumption, low cost and point of care testing) make this
      methodology very attractive in this field.

PMID- 29332803
TI  - Particle-based immobilized enzymatic reactors in microfluidic chips.
AB  - The research and applications of immobilized enzyme reactors (IMERs) have become
      more and more widespread due to the numerous advantages like reusability, easy
      handling, prolonged lifetime, easy separation from products and substrate
      specificity. The miniaturized form of these reactors (microchip IMERs) received
      outstanding attention due to their special features and advantages over the
      traditional, larger analytical systems. Large specific surface is essential for
      the efficient operation of the microreactors, thus these devices include one of
      the several types of porous solid supports, but in this work only the particle
      based microchip IMERs are reviewed. A very large variety of micro- or
      nanoparticles (beads) have been used in the microchip IMERs, however,
      incorporating these particles into microchips is still a challenge, because the
      common procedures used for the preparation of chromatographic columns are not
      well applicable at the microscopic level. Many detection systems were applied
      with microchip IMERs using on-chip or off-chip arrangement. The combination of
      microchip IMERs with mass spectrometry is particularly popular, because in these
      systems high-throughput analysis can be achieved by which the proteomic studies
      can be largely accelerated. In most chip IMER-MS systems, the chips are used for
      sample pretreatment including analyte (protein) digestion, preconcentration of
      analyte, removal of matrix materials. Additional applications of the IMERs - like
      the rapid protein digestion with proteolytic enzymes, the transformation of
      analytes to a more easily or more sensitively measurable form (detection signal
      amplification) and the design of microarrays/biosensors to analyze antigens based
      on specific interactions in immunoanalytical studies - are also reviewed.

PMID- 29332804
TI  - Effect of preprocessing high-resolution mass spectra on the pattern recognition
      of Cannabis, hemp, and liquor.
AB  - High-resolution mass spectrometry (HRMS) combined with pattern recognition was
      used to discriminate among twenty-five Cannabis samples, twenty hemp samples, and
      eight liquor samples. The effects of preprocessing on multivariate data analysis
      were evaluated for Orbitrap high-resolution mass spectra. Different root
      transformations were evaluated with respect to the bin width and the average
      classification rates. In addition, linear binning and proportional binning with
      various resolving powers were studied with respect to the average classification
      rates. The proportional binning with the square root transformation gave the best
      overall performance for chemical profiling or spectral fingerprinting. Six
      classification methods, fuzzy rule-building expert system (FuRES), linear
      discriminant analysis (LDA), super partial least squares discriminant analysis
      (sPLS-DA), support vector machine (SVM), SVM classification tree type gap
      (SVMTreeG), and SVM classification tree type entropy (SVMTreeH) had similar
      trends in prediction rate with respect to the resolving power. The optimal
      proportional mass bin width may depend on the data set, i.e., for the Cannabis
      samples is resolving power 10-4, for the hemp samples and the liquor samples are
      resolving power 10-3. Hence, data preprocessing methods such as different
      transformations, binning strategies, and resolving powers are important factors
      to be optimized for HRMS direct infusion measurements combined with pattern
      recognition to be an authentication and characterization tool for various
      products.

PMID- 29332805
TI  - Trends of non-destructive analytical methods for identification of biodiesel
      feedstock in diesel-biodiesel blend according to European Commission Directive
      2012/0288/EC and detecting diesel-biodiesel blend adulteration: A brief review.
AB  - Discrimination of biodiesel feedstock present in diesel-biodiesel blend is
      challenging due to the great similarity in the spectral profile as well as
      digital image profile of each type of feedstock employed in biodiesel production.
      Once the marketed diesel-biodiesel blend is subsidized, in which motivates
      adulteration in biofuel blend by cheaper supplies with high solubility to obtain
      profits associated with the subsidies involved in biodiesel production. Non
      destructive analytical methods based on qualitative and quantitative analysis for
      detecting marketed diesel-biodiesel blend adulteration are reviewed. Therefore,
      at the end is discussed the advantage of the qualitative analysis over
      quantitative analysis, when the systems require immediate decisions such as to
      know if the marketed diesel-biodiesel blend is unadulterated or adulterated in
      order to aid the analyst in selecting the most appropriate green analytical
      procedure for detecting diesel-biodiesel blend adulteration proceeding in fast
      way. This critical review provides a brief review on the non-destructive
      analytical methods reported in scientific literature based on different first
      order multivariate calibration models coupled with spectroscopy data and digital
      image data to identify the type of biodiesel feedstock present in diesel
      biodiesel blend in order to meets the strategies adopted by European Commission
      Directive 2012/0288/EC as well as to monitoring diesel-biodiesel adulteration.
      According to that Directive, from 2020 biodiesel produced from first-generation
      feedstock, that is, oils employed in human food such as sunflower, soybean,
      rapeseed, palm oil, among other oils should not be subsidized. Therefore, those
      non-destructive analytical methods here reviewed are helpful for discrimination
      of biodiesel feedstock present in diesel-biodiesel blend according to European
      Commission Directive 2012/0288/EC as well as for detecting diesel-biodiesel blend
      adulteration.

PMID- 29332806
TI  - Defects regulating of graphene ink for electrochemical determination of ascorbic
      acid, dopamine and uric acid.
AB  - A simple water immersing treatment has been established for regulating the
      electrocatalytic activity of commercial graphene ink. This process enables to
      remove additives in graphene ink and consequently expose the surface defects. A
      graphene ink coated glass has been fabricated as an example platform for
      simultaneous determination of ascorbic acid (AA), dopamine (DA), and uric acid
      (UA). Cyclic voltammetry studied indicated electrocatalytic reaction can be
      initiated after the additives leaching during the water immersing treatment.
      Under optimal conditions, the linear calibration curves were achieved in the
      range of 50-1000, 3-140, and 0.5-150MUM, with detection limits of 17.8, 1.44 and
      0.29MUM for AA, DA, and UA, respectively. This work demonstrated that the removal
      of additives of the graphene ink after film coating could be applied as a simple
      and cost-effective electrochemical platform for sensing application.

PMID- 29332807
TI  - Preliminary survey of matrix effects in the Microwave-sustained, Inductively
      Coupled Atmospheric-pressure Plasma (MICAP).
AB  - Matrix effects caused by Na and Al in the nitrogen Microwave-sustained,
      Inductively Coupled, Atmospheric-pressure Plasma (MICAP) were investigated.
      Easily ionizable elements, such as Na, can suppress or enhance the analyte
      signal; Al is shown here to produce a similar effect. The influence of these
      matrices was examined for 18 emission lines of 8 analyte atoms and ions having a
      wide range of excitation and ionization energies. The plasma operating conditions
      were fixed during all experiments at a total nitrogen flow of 19.4Lmin-1 and a
      microwave power of 1.5kW. An Fe solution was used to determine the excitation
      temperature of the plasma by the Boltzmann plot method at selected matrix
      concentrations. In addition, vertical emission profiles of the plasma were
      measured. The matrix effect becomes worse at higher concentrations of an easily
      ionizable element. The effect is caused not only by a shift in ionization
      equilibrium but also by a possible change in plasma ionization temperature.
      Correction methods to reduce the matrix effects were tested and are discussed.

PMID- 29332808
TI  - A polyethyleneimine-modified attapulgite as a novel solid support in matrix solid
      phase dispersion for the extraction of cadmium traces in seafood products.
AB  - In current study, a new polyethyleneimine (PEI)-modified attapulgite material was
      prepared serving as a solid support in matrix solid-phase dispersion for the
      extraction and determination (by atomic absorption spectrometry) of cadmium in
      seafood products. The major factors affecting PEI grafting were optimized using
      various PEI amounts and molecular weights. Parameters pivotal to MSPD extraction
      efficiency, like: pH, volume of eluting solvent, and the sorbent mass-to-sample
      ratio were investigated. Quantitative recoveries were achieved with 0.21g of fish
      sample, 0.13g of PEI-modified attapulgite dispersing agent, and 50% HNO3 eluting
      solution. The limit of detection and the limit of quantification were found to be
      2.5 and 8.3MUgkg-1 for cadmium in surimi samples, respectively. The recoveries
      were in the range of 89.2-100.1%, with RSDs ranged from 3.0% to 7.9% (n = 5).
      When compared to the method stipulated by the Chinese National Standard GB
      5009.15-2014, the newly developed MSPD provides comparable accuracy and even
      better repeatability for the analysis of the cadmium in real seafood samples.

PMID- 29332809
TI  - Peroxidase-catalyzed chemiluminescence system and its application in immunoassay.
AB  - Peroxidases are widely used as catalysts in chemiluminescence (CL) reaction
      because of their excellent catalytic activity and various selectable species,
      such as horseradish peroxidase (HRP), sweet potato peroxidase (SPP) and soybean
      peroxidase (SbP). They have been employed in many different CL systems for the
      determination of hydrogen peroxidase (H2O2), nucleic acid, protein and so on. In
      this paper, the application of peroxidases in the most commonly used luminol-H2O2
      CL system was reviewed from two aspects of horseradish peroxidase (HRP) and some
      anionic peroxidases. Thereinto, some enhancers used into HRP-catalyzed luminol
      H2O2 CL system for higher sensitivity and lower detection limit were discussed
      according to their classification. The employment of some anionic peroxidases
      such as SPP and SbP in luminol-H2O2 CL system was also presented. The addition of
      some specific enhancers into anionic peroxidase catalyzed luminol-H2O2 system
      could lead to an increased light intensity and a relatively long-term stable
      signal. The mechanism of all these enhanced luminol-H2O2 CL reaction and the
      foundation of their analytical application were provided and reviewed in detail.
      Finally, combined with the magnetic beads or nanoparticles as well as other
      technologies, the characteristics of peroxidase-based luminol-H2O2 CL system were
      summarized.

PMID- 29332810
TI  - Sensitive fluorescence sensing of T4 polynucleotide kinase activity and
      inhibition based on DNA/polydopamine nanospheres platform.
AB  - 5'-Polynucleotide kinase (PNK) is a crucial enzyme that catalyzes the
      phosphorylation of nucleic acid with 5'-OH termini and this phosphorylation
      reaction has been involved in many important cellular activities. The evaluation
      of PNK activity has received an increasing attention due to the significance of
      PNK. Here, the polydopamine nanospheres (PDANS) could adsorb single-stranded DNA
      (ssDNA) through pi-pi stacking or hydrogen bonding between nucleobases and
      aromatic groups of PDANS, while the interaction between double-stranded DNA
      (dsDNA) with PDANS was weakened due to the changed conformation. Hence, a novel
      DNA/PDANS platform was constructed for the sensitive and selective determination
      of T4 PNK activity based on the preferential binding properties of PDANS for
      ssDNA over dsDNA and the excellent fluorescence quenching property of PDANS. The
      dye-labeled dsDNA was phosphorylated by T4 PNK and then digested by lambda
      exonuclease, yielding dye-labeled ssDNA, which would be adsorbed on the surface
      of the PDANS and the fluorescence was greatly quenched by PDANS. Because of the
      preferential binding properties of PDANS for ssDNA over dsDNA and the high
      quenching property of PDANS, the developed DNA/PDANS platform exhibited good
      analytical performance for T4 PNK sensing in complex biological matrix and
      applied to screening inhibitors. The proposed DNA/PDANS based platform is
      promising in developing high-throughput assays for drug screening and clinical
      diagnostics.

PMID- 29332811
TI  - Manufacture and application of RuO2 solid-state metal-oxide pH sensor to common
      beverages.
AB  - A new reproducible solid-state metal-oxide pH sensor for beverage quality
      monitoring is developed and characterised. The working electrode of the developed
      pH sensor is based on the use of laser-etched sputter-deposited RuO2 on Al2O3
      substrate, modified with thin layers of sputter-deposited Ta2O5 and drop-cast
      Nafion for minimisation of redox interference. The reference electrode is
      manufactured by further modifying a working electrode with a porous polyvinyl
      butyral layer loaded with fumed SiO2. The developed pH sensor shows excellent
      performance when applied to a selection of beverage samples, with a measured
      accuracy within 0.08 pH of a commercial glass pH sensor.

PMID- 29332812
TI  - Thrombodynamics, a new global coagulation test: Measurement of heparin
      efficiency.
AB  - The actual coagulation status may be reliably measured using only highly
      sensitive global functional tests; however, they are not numerous and all of them
      have disadvantages. Thrombodynamics (TD), a novel global coagulation test, is
      sensitive to hypo- and hypercoagulable states. The main properties of this test
      were investigated, and its capabilities for hemostasis analysis were verified
      through pharmacodynamic monitoring of the most widely used anticoagulants,
      heparins. The anticoagulant effects in the plasma of donors (n = 20) and patients
      after hip replacement (n = 20) spiked with unfractionated heparin or enoxaparin
      were measured in vitro to eliminate the influence of pharmacokinetic factors.
      Sensitivity for heparins was compared for activated partial thromboplastin time,
      thrombin generation tests and TD. TD was shown to reliably characterize the
      pharmacodynamics of any heparin in the entire range of its prophylactic and
      therapeutic concentrations. Inter-individual variability for the anticoagulant
      action of heparins was also calculated using the TD data. This variability did
      not differ between the investigated groups and did not exceed 12% and 20% for the
      stationary clot growth rate in the presence of unfractionated heparin and
      enoxaparin, respectively. That finding was in accordance with the values
      determined earlier using the thrombin generation test. The study results showed
      that TD has advantages over the other global methods of coagulation analysis.
      These advantages are good standardization, high reproducibility, independence of
      the parameter values from patient age and gender, and a narrower parameter
      distribution in a normal population. These results indicate that TD is a
      promising universal assessment method that improves the quality of hemostasis
      analysis because it more reliably detects deviations from the parameters'
      reference values.

PMID- 29332813
TI  - Fast and easy extraction of antidepressants from whole blood using ionic liquids
      as extraction solvent.
AB  - This study aims to prove that ionic liquids (ILs) can be used as extraction
      solvents in a liquid-liquid microextraction, coupled to LC-MS/MS, for the
      quantification of a large group of antidepressants in whole blood samples. The
      sample preparation procedure consisted of adding 1.0mL aqueous buffer pH 3.0 and
      60uL of IL (1-butyl-3-methylimidazolium hexafluorophosphate) to 1.0mL whole
      blood. Subsequently, a 5-min rotary mixing step was performed followed by
      centrifugation. The lower IL phase was collected, diluted 1:10 in methanol and
      10uL was injected into the LC-MS/MS. The following analytes were included in the
      full-quantitative method: agomelatine, amitriptyline, bupropion, clomipramine,
      dosulepin, doxepin, duloxetine, escitalopram, fluoxetine, imipramine,
      maprotiline, mianserin, mirtazapine, nortriptyline, paroxetine, reboxetine,
      trazodone and venlafaxine. Selectivity was checked for 10 different whole blood
      matrices. Additionally, possible interferences of deuterated standards or other
      antidepressants were evaluated. Overall, no interferences were found. For each
      analyte a matrix-matched calibration curve was constructed (7 levels, n = 6),
      covering therapeutic and low toxic concentrations. Accuracy and precision were
      evaluated over eight days, at three concentration levels (n = 2). Bias,
      repeatability and intermediate precision results met with the proposed validation
      criteria, except for fluvoxamine, which was therefore only included in the semi
      quantitative method. LOQs were set at the lowest calibrator concentration and LOD
      values were - for most analytes - within a range of 1-2ng/mL. Recoveries (RE) and
      matrix effects (ME) were evaluated for five types of donor whole blood, at two
      concentration levels. RE values were within a range of 53.11-132.98%. ME values
      were within a range of 61.92-123.24%. In conclusion, this study proves the
      applicability of ILs as extraction solvents for a large group of antidepressants
      in complex whole blood matrices.

PMID- 29332814
TI  - Novel S, N-doped carbon quantum dot-based "off-on" fluorescent sensor for silver
      ion and cysteine.
AB  - In this work, sulfur and nitrogen co-doped carbon dots (S,N-CQDs) as highly
      selective fluorescent probe for silver ion (Ag+) and cysteine (Cys) detection
      were designed and synthesized directly from citric acid and thiamine
      hydrochloride via a one-step hydrothermal protocol in 63.8% quantum yield. This
      probe enabled selective detection of Ag+ with a linear range of 0-10 and 10
      250MUM and a limit of detection of 0.40MUM with respect to the variation in
      fluorescence induced by target concentration and electron-transfer from S,N-CQDs
      to Ag+. Furthermore, S,N-CQDs/Ag+ fluorescence can be effectively recovered by
      virtue of a specific reaction of Cys with silver ion. This fluorescence "turn-on"
      protocol was applied to determine Cys with two linear ranges of 0-10 and 10
      120MUM as well as a detection limit of 0.35MUM. The corresponding cell
      experiments were also performed, indicating that the prepared S,N-CQDs possessed
      low cytotoxicity and good biocompatibility. Ultimately, the practicality and
      viability of this fluorescent probe were demonstrated through the analysis of
      silver ion in real river water and human serum samples.

PMID- 29332815
TI  - Single particle analysis of TiO2 in candy products using triple quadrupole ICP
      MS.
AB  - Titanium dioxide (TiO2) belongs to the materials that have gained great
      importance in many applications. In its particulate form (micro- or
      nanoparticles), it has entered a huge number of consumer products and food-grade
      TiO2, better known as E171 within the European Union, represents an important
      food additive. Thus, there is an increasing need for analytical methods able to
      detect and quantify such particles. In this regard, inductively coupled-mass
      spectrometry (ICP-MS), in particular single particle ICP-MS (spICP-MS), has
      gained importance due to its simplicity and ease of use. Nevertheless, the number
      of applications for Ti nanoparticles is rather limited. In this study, we have
      applied the spICP-MS strategy by comparing different measuring modes available in
      triple quadrupole ICP-MS. First, single quadrupole mode using the
      collision/reaction cell system was selected for monitoring the isotope 47Ti.
      Different cell gases like He, O2 and NH3 were tested under optimised conditions
      for its applicability in spICP-MS of standard suspensions of TiO2. The determined
      analytical figures of merit were compared to those obtained by triple quadrupole
      mode using the 47Ti or 48Ti reaction products using O2 and NH3 as reaction gases.
      This comparison demonstrated that the triple quadrupole mode (TQ mode) was
      superior in terms of sensitivity due to the more efficient removal of spectral
      interferences. Particle size detection limits down to 26nm were obtained using
      the best instrumental conditions for TiO2 particles at a dwell time of 10ms.
      Finally, the different measuring modes were applied to the analysis of chewing
      gum samples after a simple extraction procedure using an ultrasonic bath. The
      obtained results showed a good agreement for the detected particle size range
      using the different TQ modes. The size range of TiO2 particles was determined to
      be between approximately 30 and 200nm, whereas roughly 40% of the particles were
      smaller than 100nm. For the determination of the particle number concentration in
      these real samples, we suggest CeO2 particles as internal standard.

PMID- 29332816
TI  - Comparative enzymatic studies using ion-selective electrodes. The case of
      cholinesterases.
AB  - The application of traditional ion-selective electrodes for comparative enzymatic
      analysis was demonstrated for the first time in this study. A kinetic
      potentiometric method based on the monitoring of the concentration of the ionic
      substrate involved in the enzymatic reaction catalyzed by different
      cholinesterases is used for this purpose. A comparative study was performed
      comprising both enzymatic assays using different ionic substrates and the
      corresponding inhibited reactions in presence of neostigmine (a synthetic
      anticholinesterase). The developed approach is used to obtain valuable
      comparative results through calculation of kinetic parameters, such as Michaelis
      and inhibition constants. Interesting results were obtained for
      acetylcholinesterase and butyrylcholinesterase enzymes, which were selected as
      proof-of-concept: (i) the binding affinity that these enzymes have for their
      natural substrates showed to be higher (acetylcholine and butyrylcholine
      respectively) than for their corresponding thiol derivatives (acetylthiocholine
      and butyrylthiocholine), which are traditionally used in spectrophotometric
      enzymatic assays; (ii) as expected, the maximum hydrolysis rate found in the
      assays of each enzyme was independent of the substrate used; (iii)
      acetylcholinesterase enzyme inhibition due to neostigmine was found to be higher
      (higher inhibition constant). Advantageously, the use of ion-selective electrodes
      permits to perform cholinesterases' enzymatic assays using their natural
      substrates and under physiological conditions, unlike the traditional
      spectrophotometric methods used in routine enzymatic assays. Importantly, while
      well-known enzymes are use throughout this work, this approach can be extended to
      other types of enzymatic assays as a tangible alternative to traditional
      spectrophotometric methods.

PMID- 29332817
TI  - Miniaturised electrically actuated high pressure injection valve for portable
      capillary liquid chromatography.
AB  - A miniaturised high pressure 6-port injection valve has been designed and
      evaluated for its performance in order to facilitate the development of portable
      capillary high performance liquid chromatography (HPLC). The electrically
      actuated valve features a very small size (65 * 19 * 19mm) and light weight
      (33g), and therefore can be easily integrated in a miniaturised modular capillary
      LC system suited for portable field analysis. The internal volume of the
      injection valve was determined as 98 nL. The novel conical shape of the stator
      and rotor and the spring-loaded rotor performed well up to 32MPa (4641psi), the
      maximum operating pressure investigated. Suitability for application was
      demonstrated using a miniaturised capillary LC system applied to the
      chromatographic separation of a mixture of biogenic amines and common cations.
      The RSD (relative standard deviation) values of retention times and peak areas of
      6 successive runs were 0.5-0.7% and 1.8-2.8% for the separation of biogenic
      amines, respectively, and 0.1-0.2% and 2.1-3.0% for the separation of cations,
      respectively. This performance was comparable with bench-top HPLC systems thus
      demonstrating the applicability of the valve for use in portable and miniaturised
      capillary HPLC systems.

PMID- 29332818
TI  - A novel dual labeling approach enables converting fluorescence labeling reagents
      into fluorogenic ones via introduction of purification tags. Application to
      determination of glyoxylic acid in serum.
AB  - Pre-column derivatization with fluorescence labeling reagents involves many
      problems including crowded chromatograms, possibility of the introduction of
      analytical errors, and poor selectivity. Herein we report a novel purification
      tag/fluorophore dual labeling approach based on a multi-component reaction to
      solve this major problem. Glyoxylic acid was recently identified as an early
      biomarker for diabetes, thus it was selected as a model analyte for our new dual
      labeling approach. Using the multi-component Petasis reaction, we could introduce
      a fluorophore (1-pyreneboronic acid, 1-PyBA) and a purification tag (taurine) to
      our target analyte (glyoxylic acid) in one step reaction. Using taurine as the
      amine reactant in Petasis reaction leads to the formation of a reaction product
      with a terminal sulfonic acid group which can be selectively retained on an anion
      exchange sorbent allowing excess fluorescent 1-PyBA reagent and its fluorescent
      decomposition products to be washed away. Then, quantification of the formed
      analyte-fluorophore-purification tag adduct was carried out by a simple isocratic
      HPLC-fluorescence detection method. The newly developed technique allowed highly
      selective, very rapid and efficient determination of glyoxylic acid in human
      serum eliminating endogenous components and excess reagent interference.
      Glyoxylic acid was determined in serum at a final concentration down to 30nM (600
      fmol/injection) with good recovery (87.0%), accuracy (- 2.2 to 9.2) and precision
      (%RSD <= 8.7).

PMID- 29332819
TI  - Chemometric analysis of NMR and GC datasets for chemotype characterization of
      essential oils from different species of Ocimum.
AB  - The genus Ocimum (Labiatae) comprises 30 species found in tropical and
      subtropical regions of the planet, of which species O. basilicum L. and O.
      gratissimum are widely used in food and traditional medicine. Phytochemical
      studies on Ocimum have revealed a number of essential oil chemotypes, for
      example, eugenol, methyl chavicol, linalool, and methyl cinnamate. Since
      essential oils are commercially assessed according to their content, the aim of
      this study was to develop a simple and precise method for their qualitative and
      quantitative analysis using NMR spectroscopy combined with chemometrics. Seven
      essential oils from different species of Ocimum, an unknown sample, and a
      commercial sample were evaluated and the results compared to those from
      established and precise GC-MS and GC-FID methods. Chemometric evaluation from
      both 1H NMR and GC-MS data revealed three chemotypes: eugenol for O. gratissimum,
      O. micranthum, and O. tenuiflorum; estragole for O. basilicum, O. basilicum var.
      purpuracens, and O. selloi; and methyl cinnamate for O. americanum. The unknown
      and commercial species were classified as cinnamate and eugenol chemotypes,
      respectively. Despite the corroborating results, the chemometric analysis
      revealed the higher robustness (better adjustment) of the 1H NMR model compared
      to the GC-MS method in terms of certain statistical parameters. The 1H NMR method
      allows for the detection and quantification of organic compounds in a complex
      mixture without the need for certified standard compounds. Although GC-MS and GC
      FID were able to detect five compounds not observed by NMR spectroscopy, the four
      most important metabolites (eugenol, estragole, methyl cinnamate, and eucalyptol)
      were more readily detected and quantified by 1H NMR.

PMID- 29332820
TI  - A strategy for screening of alpha-glucosidase inhibitors from Morus alba root
      bark based on the ligand fishing combined with high-performance liquid
      chromatography mass spectrometer and molecular docking.
AB  - A new method based on ligand fishing combined with high-performance liquid
      chromatography quadrupole-time-of-flight mass spectrometer and molecular docking
      was established to screen alpha-glucosidase inhibitors from a traditional Chinese
      medicine Morus alba root bark. alpha-Glucosidase was immobilized on magnetic
      nanoparticles, used as a solid support to incubate with crude extract. After
      ligand fishing, the eluates were analyzed by high-performance liquid
      chromatography quadrupole-time-of-flight mass spectrometer, obtaining eleven
      ligands (1-4, 6-12) eventually. In order to discriminate the non-specific binders
      and discover powerful enzyme inhibitors, molecular docking was further performed
      and three of the eleven ligands were optimized to be excellent alpha-glucosidase
      inhibitors by the confirmation of isolation and bioassay of individual compounds.
      These three ligands, sanggenons G (6), O (7) and sanggenol G (12) exhibited
      striking inhibitory activities with extremely low IC50 values. The results
      suggest that established method will be applied to a wide range of target protein
      to screen potential bioactive constituents from herbal medicines.

PMID- 29332821
TI  - Determination of pyrophosphate and sulfate using polyhexamethylene guanidine
      hydrochloride-stabilized silver nanoparticles.
AB  - Positively charged polyhexamethylene guanidine hydrochloride-stabilized silver
      nanoparticles (PHMG-AgNPs) were prepared and applied as a colorimetric probe for
      single-step determination of pyrophosphate and sulfate. The approach is based on
      the nanoparticles aggregation leading to change in their absorption spectra and
      color of the solution. Due to both electrostatic and steric stabilization these
      nanoparticles show decreased sensitivity relatively to many common anions, which
      allows for simple and rapid direct single-step determination of pyrophosphate and
      sulfate. Effects of different factors (time of interaction, pH, concentrations of
      anions and the nanoparticles) on aggregation of PHMG-AgNPs and analytical
      performance of the procedure were investigated. The method allows for the
      determination of pyrophosphate and sulfate in the range of 0.16-2MUgmL-1 and 20
      80MUgmL-1 with RSD of 2-5%, respectively. The analysis can be performed using
      either spectrophotometry or naked-eye detection. Practical application of the
      method was shown by the example of pyrophosphate determination in baking powder
      sample.

PMID- 29332822
TI  - Constituting fully integrated colorimetric analysis system for Fe(III) on
      multifunctional nitrogen-doped MoO3/cellulose paper.
AB  - Using ammonium molybdate and thiourea as precursors, nitrogen-doped MoO3 was
      produced by a one-step carbonization and then fixed into the cellulose filter
      paper (NMCP) with acrylic resin as a fixative. NMCP was designed as a
      multifunctional nanocomposite, i.e., solid phase adsorbent for Fe(III)
      preconcentration, photocatalyst for iron species transformation and color
      interference removal, and colorimetric sensor for Fe(III) determination. After
      photocatalysis, the complex of Fe-humic substances could be transformed into
      Fe(III) ions, the interference of colored organic matter (e.g., aqueous humic
      substance) was removed, Fe(III) was enriched selectively onto NMCP with the
      coexistence of interference metal ions (e.g. Co(II) and Cd(II)) and then
      transformed into Fe(II) by hydroxylamine and photoreduction and for colorimetric
      analysis. The obstacle of o-phenanthroline colorimetric method was overcome. The
      photodegradation activity of MoO3 was improved 2.02 times by nitrogen doping with
      the optimal mass ratio, which was also 5.11 times of P25-TiO2. The concentration
      of Fe(III) on NMCP was quantified by the gray-scale using smart phones and image
      processing software, without complicated equipment. Based on multifunctional
      NMCP, a fully integrated visual analysis system was proposed and suitable for the
      field detection of Fe(III) in natural water. The log-linear calibration curve for
      Fe(III) was in the range of 0.05-5mg/L with a determination coefficient (R2) of
      0.976 and detection limit of 15MUg/L.

PMID- 29332823
TI  - A combination of computational-experimental study on metal-organic frameworks MIL
      53(Al) as sorbent for simultaneous determination of estrogens and glucocorticoids
      in water and urine samples by dispersive micro-solid-phase extraction coupled to
      UPLC-MS/MS.
AB  - In this work, computational and experimental methods were used to study the
      adsorption of estrogens and glucocorticoids on metal-organic frameworks (MOFs).
      Computer-aided molecular simulation was applied to predict the adsorption of
      eight analytes on four MOFs (MIL-101(Cr), MIL-100(Fe), MIL-53(Al), and UiO
      66(Zr)) by examining molecular interactions and calculating free binding
      energies. Subsequently, the four water-stable MOFs were synthesized and evaluated
      as adsorbents for the target hormones in aqueous solution. As the MOF exhibiting
      the highest adsorption capacity in both computations and experiments, MIL-53(Al)
      was chosen as a sorbent to develop a dispersive micro-solid-phase extraction
      procedure coupled to ultra-performance liquid chromatography tandem mass
      spectrometry for simultaneous determination of the target analytes in water and
      human urine samples. Experimental parameters affecting the extraction recoveries,
      including pH, ionic strength, MIL-53(Al) amount, extraction time, desorption
      time, and desorption solvent, were optimized. The optimized method provided a
      linear range of 0.005025-368.6MUg/L with good correlation coefficients (0.9982 <=
      r2 <= 0.9992), and limits of detection (S/N = 3) and quantification (S/N = 10) of
      0.0015-1.0MUg/L and 0.005-1.8MUg/L, respectively. The analyte recoveries were in
      the range of 80.6-98.4% in water samples and 88.4-93.2% in urine samples.
      Furthermore, MIL-53(Al) showed good stability over 10 extraction cycles (RSD <
      10.0%). Good agreement between experimental measurements and computational
      results showed the potential of this approach for elucidating adsorption
      mechanisms and predicating extraction efficiencies for MOFs and targets,
      providing new directions for the development and utilization of MOFs.

PMID- 29332824
TI  - Dithiothreitol-based protein equalization technology to unravel biomarkers for
      bladder cancer.
AB  - This study aimed to assess the benefits of dithiothreitol (DTT)-based sample
      treatment for protein equalization to assess potential biomarkers for bladder
      cancer. The proteome of plasma samples of patients with bladder carcinoma,
      patients with lower urinary tract symptoms (LUTS) and healthy volunteers, was
      equalized with dithiothreitol (DTT) and compared. The equalized proteomes were
      interrogated using two-dimensional gel electrophoresis and matrix assisted laser
      desorption ionization time of flight mass spectrometry. Six proteins, namely
      serum albumin, gelsolin, fibrinogen gamma chain, Ig alpha-1 chain C region, Ig
      alpha-2 chain C region and haptoglobin, were found dysregulated in at least 70%
      of bladder cancer patients when compared with a pool of healthy individuals. One
      protein, serum albumin, was found overexpressed in 70% of the patients when the
      equalized proteome of the healthy pool was compared with the equalized proteome
      of the LUTS patients. The pathways modified by the proteins differentially
      expressed were analyzed using Cytoscape. The method here presented is fast,
      cheap, of easy application and it matches the analytical minimalism rules as
      outlined by Halls. Orthogonal validation was done using western-blot. Overall,
      DTT-based protein equalization is a promising methodology in bladder cancer
      research.

PMID- 29332825
TI  - Development of Gd3+-immobilized glutathione-coated magnetic nanoparticles for
      highly selective enrichment of phosphopeptides.
AB  - In this study, we designed a gadolinium-based immobilized metal ion affinity
      chromatography material for the selective enrichment of phosphopeptides.
      Gadolinium ion was immobilized on the surface of glutathione-coated magnetic
      nanoparticles through a facile and effective synthetic route. The adsorbent
      integrated the advantages of superparamagnetism of Fe3O4 core, good biological
      compatibility of glutathione, and strong interaction between gadolinium ion and
      phosphopeptides. It was employed to enrich phosphopeptides from standard protein
      digests coupled with MALDI-TOF MS. Results demonstrated that the adsorbent
      possessed high selectivity for phosphopeptides, good reusability and
      reproducibility. Moreover, the material provided selective enrichment of
      phosphopeptides from real samples including non-fat milk digests and human serum.
      The developed method exhibited high sensitivity (detection limit of 10 fmol),
      showing great potential in the detection of low-abundance phosphopeptides in
      biological samples.

PMID- 29332826
TI  - A robust and extendable sheath flow interface with minimal dead volume for
      coupling CE with ESI-MS.
AB  - In this paper, we describe a robust sheath flow-based CE-MS interface with
      minimal interface dead volume based on an extended pattern. A 20um i.d. * 90um
      o.d. fused-silica capillary with a chemically-etched thin-wall tip (30um o.d.)
      was used as the separation capillary as well as electrospray emitter, and a 200um
      i.d. * 375um o.d. capillary with a tapered tip (40um o.d.) was used as the sheath
      flow capillary. An extendable sheath-flow interface mode was adopted by
      decreasing the thickness of separation capillary tip and extending the separation
      capillary tip out from the sheath flow capillary tip, and allowing the sheath
      flow to be transferred to the separation capillary tip along its outer surface,
      forming a surface sheath flow to mix with sample flow at the separation capillary
      tip. Such a strategy could significantly reduce the interface dead volume and
      thus improve the CE separation efficiency and detection sensitivity, as well as
      evidently enhance the working reliability of the CE-MS interface. We investigated
      various factors affecting the interface performance, including capillary
      extending distance, emitter diameters, sheath flow capillary shape, and sheath
      flow rate. Under the optimized conditions, a minimal interface dead volume of ca.
      4pL was obtained which is the smallest one compared with previously-reported
      sheath flow-based CE-MS interfaces. The feasibility and applicability of the
      present CE-MS interface were demonstrated in the separation of a peptide mixture
      with high separation efficiency of 2.07-3.38um plate heights and good
      repeatabilities (< 6.1% RSD, n = 5). We except such a simple and robust interface
      could provide a possible solution for the development of commercial CE-MS
      interfaces differing from the currently-used ones, and has the potentials to be
      applied in routine analytical laboratories for various studies such as
      proteomics, metabolomics, or single cell analysis.

PMID- 29332827
TI  - Rapid and sensitive detection of malachite green in aquaculture water by
      electrochemical preconcentration and surface-enhanced Raman scattering.
AB  - A highly sensitive and rapid method of in-situ surface-enhanced Raman
      spectroscopy (SERS) combining with electrochemical preconcentration (EP) in
      detecting malachite green (MG) in aquaculture water was established. Ag
      nanoparticles (AgNPs) were synthesized and spread onto the surface of gold
      electrodes after centrifuging to produce SERS-active substrates. After optimizing
      the pH values, preconcentration potentials and times, in-situ EP-SERS detection
      was carried out. A sensitive and rapid analysis of the low-concentration MG was
      accomplished within 200s and the limit of detection was 2.4 * 10-16M.

PMID- 29332828
TI  - UPLC-MS/MS analysis for antioxidant components of Lycii Fructus based on spectrum
      effect relationship.
AB  - Lycii Fructus is widely cultivated in the Northwest China. It is well-known for
      its antiaging effect in traditional Chinese medicines (TCMs), but the effective
      components are not clear. In this work, the ultra-performance liquid
      chromatography tandem mass spectrometry (UPLC-MS/MS) was used to study the
      antioxidant components of Lycii Fructus through analyzing the spectrum-effect
      relationship, and the positive correlation components with antioxidant activity
      were partially identified. The extractums of Lycii Fructus were adsorbed with
      macroporous resin, and then eluted with water and 30%, 60%, 90% ethanol in turn.
      The extract fraction eluted with 60% ethanol was determined as the best, and was
      taken for subsequent experiments. With the above separation method, UPLC
      fingerprints of thirty batches of Lycii Fructus (from different areas) were
      obtained, and thirty common peaks were selected through similarity analysis (SA).
      Combined with the data of the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino
      bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) assays, the
      spectrum-effect relationship was studied. The results showed that the main peaks
      with antioxidant activity were P14, P26, P8, and P21 for DPPH, and P26, P14, P21,
      and P19 for ABTS. Using the UPLC-MS/MS data, peaks P14, P19, P21, and P30 were
      respectively identified as chlorogenic acid, quercetin, kaempferol, and
      isorhamnetin, and then the results were confirmed through comparison with the
      standards and other references. Finally, their strong antioxidant activities were
      validated experimentally.

PMID- 29332829
TI  - Synchronous detection of ebolavirus conserved RNA sequences and ebolavirus
      encoded miRNA-like fragment based on a zwitterionic copper (II) metal-organic
      framework.
AB  - From a three-dimensional (3D) metal-organic framework (MOF) of
      {[Cu(Cmdcp)(phen)(H2O)]2.9H2O}n (1, H3CmdcpBr = N-carboxymethyl-(3,5
      dicarboxyl)pyridinium bromide, phen = phenanthroline), a sensitive and selective
      fluorescence sensor has been developed for the simultaneous detection of
      ebolavirus conserved RNA sequences and ebolavirus-encoded microRNA-like (miRNA
      like) fragment. The results from molecular dynamics simulation confirmed that MOF
      1 absorbs carboxyfluorescein (FAM)-tagged and 5(6)-carboxyrhodamine,
      triethylammonium salt (ROX)-tagged probe ss-DNA (probe DNA, P-DNA) by pi...pi
      stacking and hydrogen bonding, as well as additional electrostatic interactions
      to form a sensing platform of P-DNAs@1 with quenched FAM and ROX fluorescence. In
      the presence of targeted ebolavirus conserved RNA sequences or ebolavirus-encoded
      miRNA-like fragment, the fluorophore-labeled P-DNA hybridizes with the analyte to
      give a P-DNA@RNA duplex and released from MOF 1, triggering a fluorescence
      recovery. Simultaneous detection of two target RNAs has also been realized by
      single and synchronous fluorescence analysis. The formed sensing platform shows
      high sensitivity for ebolavirus conserved RNA sequences and ebolavirus-encoded
      miRNA-like fragment with detection limits at the picomolar level and high
      selectivity without cross-reaction between the two probes. MOF 1 thus shows the
      potential as an effective fluorescent sensing platform for the synchronous
      detection of two ebolavirus-related sequences, and offer improved diagnostic
      accuracy of Ebola virus disease.

PMID- 29332830
TI  - Novel approach in k0-NAA for highly concentrated REE Samples.
AB  - The present paper presents a new approach for k0-NAA for accurate quantification
      with short turnaround analysis times for rare earth elements (REEs) in high
      content mineral matrices. REE k0 and Q0 values, spectral interferences and
      nuclear interferences were experimentally evaluated and improved with Alfa Aesar
      Specpure Plasma Standard 1000mgkg-1 mono-rare earth solutions. The new iterative
      gamma-ray self-attenuation and neutron self-shielding methods were investigated
      with powder standards prepared from 100mg of 99.9% Alfa Aesar mono rare earth
      oxide diluted with silica oxide. The overall performance of the new k0-NAA method
      for REEs was validated using a certified reference material (CRM) from Canadian
      Certified Reference Materials Project (REE-2) with REE content ranging from
      7.2mgkg-1 for Yb to 9610mgkg-1 for Ce. The REE concentration was determined with
      uncertainty below 7% (at 95% confidence level) and proved good consistency with
      the CRM certified concentrations.

PMID- 29332831
TI  - Corrigendum to, Carboxylated carbon nanospheres as solid-phase extraction
      adsorbents for the determination of perfluorinated compounds in water samples by
      liquid chromatography-tandem mass spectrometry' [Talanta 178 (2018) 129-133].

PMID- 29332832
TI  - Electrochemiluminescent detection of cardiac troponin I by using soybean
      peroxidase labeled-antibody as signal amplifier.
AB  - This work proposed an electrochemiluminescence (ECL) immunosensor for
      quantitative monitoring of cardiac troponin I (cTnI) in plasma with soybean
      peroxidase (SBP) labeled-antibody as signal amplifier. The ECL sandwich
      immunosensor was constructed by covalent binding anti-cTnI capture antibody (Ab1)
      to polyethylenimine-functionalized graphene matrix, which was obtained by a
      simple hydrothermal reaction between polyethylenimine (PEI) and graphene oxide
      (GO). After that, the SBP-labeled detection antibody (SBP-Ab2), synthesized by
      NaIO4 method, was immobilized on the surface of electrode through sandwich
      immunoreaction. The SBP on electrode surface displayed strong and stable ECL
      signal of luminol in the presence of H2O2, which could be used for cTnI detection
      with a concentration range of 5-30,000pg/mL and a detection limit of 3.3pg/mL.
      This proposed SBP-modified immunosensor displayed high sensitivity, selectivity
      and accuracy, and was expected not only to detect cTnI in practical human plasma
      sample but also to be used in other biomarkers detection.

PMID- 29332833
TI  - A combination of "thiol-ene" click chemistry and surface initiated atom transfer
      radical polymerization: Fabrication of boronic acid functionalized magnetic
      graphene oxide composite for enrichment of glycoproteins.
AB  - An efficient glycoproteins enrichment platform is one of vital preprocessing
      steps in biomarker research and in particular glycoproteomics. In this work, a
      well-defined boronic acid functionalized magnetic graphene oxide nanocomposite
      (Fe3O4-GO@PAAPBA) was synthesized for the selective enrichment of glycoproteins
      from complex biological samples via a novel strategy based on the "thiol-ene"
      click chemistry and surface initiated atom transfer radical polymerization (SI
      ATRP). The initiator of ATRP was anchored to the surface of substrate through
      "thiol-ene" click reaction. The product Fe3O4-GO@PAAPBA was successfully
      synthesized in following SI-ATRP. The Fe3O4-GO@PAAPBA nanocomposite was
      characterized by transmission electron microscopy (TEM), Fourier transform
      infrared spectroscopy (FTIR), X-ray diffraction (XRD), X-ray photoelectron
      spectroscopy (XPS), vibrating sample magnetometry (VSM) and thermogravimetric
      analysis. The adsorption capacity of Fe3O4-GO@PAAPBA towards ovalbumin (OVA) and
      transferrin (Trf) is 471mgg-1 and 450mgg-1, respectively. The nanocomposite also
      featured good selectivity to glycoproteins in the mixture of glycoproteins and
      non-glycoproteins at alkaline (pH 9.0) and physiological conditions (pH 7.4).
      Furthermore, it can be applied to extract glycoproteins directly from egg white
      samples. These results have indicated that Fe3O4-GO@PAAPBA was a potential
      affinity material in glycoprotein analysis.

PMID- 29332834
TI  - Direct inlet probe ion mobility spectrometry.
AB  - Direct inlet probe (DIP) was used as an introduction and a pre-separation step
      for atmospheric pressure photoionization time-of-flight ion mobility spectrometry
      (APPI-TOF-IMS) for the first time. IMS is an analytical technique used to
      separate and identify ionized molecules in the gas phase and under atmospheric
      pressure based on their mobility. The utilization of DIP prior to IMS gives the
      possibility to introduce the analytes into the gas phase and provides an
      additional separation based on their vapor pressure. The proof-of-principle study
      was done on example of eight polycyclic aromatic hydrocarbons (PAHs) with the
      ring number from 2 to 5, namely naphthalene, fluorene, anthracene, phenanthrene,
      pyrene, fluoranthene, benzo[a]pyrene, and benzo[k]fluoranthene. All these
      compounds are included in EPA priority pollutant list. Moreover, benzo[a]pyrene
      and benzo[k]fluoranthene are marked by EPA as probably carcinogen compounds and
      also included into SCF and EU lists. To increase the sensitivity of DIP-APPI-IMS
      the analysis was performed using a dopant assisted ionization method (benzene,
      74mgL-1 in N2). It was found that the heating rate of the interface plays a
      crucial role for the whole analytical procedure. To prove the ability of this
      method to analyze PAHs in the mixture, the mixtures containing up to five PAHs
      were analyzed. The LODs for the analyzed compounds obtained with DIP-APPI-IMS
      were found to be in the tens- or hundreds-of-microgram-per-liter range. The
      obtained results are promising enough to ensure the potential of DIP as an
      introduction and a pre-separation step for ion mobility based methods.

PMID- 29332835
TI  - Varietal discrimination of hop pellets by near and mid infrared spectroscopy.
AB  - Hop is one of the most important ingredients of beer production and several
      varieties are commercialized. Therefore, it is important to find an eco-real-time
      friendly-low-cost technique to distinguish and discriminate hop varieties. This
      paper describes the development of a method based on vibrational spectroscopy
      techniques, namely near- and mid-infrared spectroscopy, for the discrimination of
      33 commercial hop varieties. A total of 165 samples (five for each hop variety)
      were analysed by both techniques. Principal component analysis, hierarchical
      cluster analysis and partial least squares discrimination analysis were the
      chemometric tools used to discriminate positively the hop varieties. After
      optimizing the spectral regions and pre-processing methods a total of 94.2% and
      96.6% correct hop varieties discrimination were obtained for near- and mid
      infrared spectroscopy, respectively. The results obtained demonstrate the
      suitability of these vibrational spectroscopy techniques to discriminate
      different hop varieties and consequently their potential to be used as an
      authenticity tool. Compared with the reference procedures normally used for hops
      variety discrimination these techniques are quicker, cost-effective, non
      destructive and eco-friendly.

PMID- 29332836
TI  - Fluorescent and colorimetric dual-mode aptasensor for thrombin detection based on
      target-induced conjunction of split aptamer fragments.
AB  - Since the lack of detection diversity of the single-signal readout strategy, it
      is urgent to develop fast and multisignal assay strategies. A highly selective
      and sensitive assay method with colorimetric and fluorometric dual signals
      readouts is presented in this paper. It is based on the principle that the target
      induced conjunction of split aptamer fragments assembled on the surface of Au
      nanoparticles (AuNPs). In the presence of targets, the color of solution changed
      from wine red to blue and can be measured both visual inspection and
      spectrophotometry because of the aggregation of AuNPs. At the same time, the
      report probes which are original hybrid with the anchoring aptamer fragments on
      the AuNPs surface can be released and recovers the fluorescence. By use of this
      detection strategy, the limit of detection for thrombin (TMB), as a model of
      analyte, were 0.45 and 0.16nM, respectively. Furthermore, this protocol can
      discriminate TMB from other analogue with high selectivity and can be used to
      detect TMB in human serum samples. The results came from the two signals were
      well consistent with each other, which demonstrated that it has application
      potential for detection of TMB in complex matrix.

PMID- 29332837
TI  - A novel electroanalytical assay for sulfamethazine determination in food samples
      based on conducting polymer nanocomposite-modified electrodes.
AB  - The toxicity of sulfa drugs has attracted great attention, and the reported
      electrochemical methods for sulfa drugs usually employ a high oxidation
      potential. In this work, a one-pot synthesized conducting polymer nanocomposite
      containing poly(3,4-ethylenedioxythiophene) (PEDOT) and MnO2 was cast on a screen
      printed carbon electrode (SPCE), and the modified electrode showed superior
      electrochemical activity over a bare electrode for sulfamethazine (SMZ)
      determination. The SMZ detection was based on the electrochemical oxidation
      product, which showed an adsorptive property and exhibited a redox couple at
      0.39V in pH 3 phosphate buffer solutions (PBS). The electrode surfaces were well
      characterized by the water contact angle technique, Raman spectroscopy, X-ray
      photoelectron spectroscopy (XPS), field emission scanning electron microscopy (FE
      SEM), atomic force microscopy (AFM) and cyclic voltammetry. By the use of square
      wave voltammetry (SWV), a wide linear response to SMZ, from 1.0uM to 500MUM, was
      obtained. The sensitivity and detection limits (S/N = 3) were 0.115MUAMUM-1 and
      0.16MUM, respectively. The proposed method and a reference high-performance
      liquid chromatographic method (HPLC) were applied for the determination of SMZ in
      two real samples using the standard addition method, and satisfactory recoveries
      and good agreement were obtained.

PMID- 29332838
TI  - Rapid and sensitive tapered-capillary microextraction combined to on-line sample
      stacking-capillary electrophoresis for extraction and quantification of two beta
      blockers in human urine.
AB  - A tapered-capillary microextraction (tCap-MUEx) combining with field-amplified
      stacking (FASI) method for CE analysis was developed. The tCap-MUEx method is
      based on the construction of a micro solid phase extraction (SPE) column by
      narrowing the end of a silica capillary from 530um (inner diameter) to 20um,
      enabling the packing of 45um sorbent particles without a frit. Various parameters
      that may affect the microextraction and FASI-CE analysis have been investigated
      and optimized. This study shows that microextraction exhibits advantages of small
      sample and sorbent volumes (less than 200MUL sample and 2MUL sorbent) and fast
      extraction time of 6min. The method was successfully applied for efficient
      determination of atenolol and metoprolol in human urine samples, with recovery of
      93.7-105.5% and RSD (n=3) lower than 8.5%. Twenty-one-fold and nineteen-fold
      average enhancement of detection sensitivity was achieved for atenolol and
      metoprolol, respectively, versus the CE method without tCap-MUEx and FASI. The
      method is environmentally friendly and allows reuse of the sorbent at least 8
      times without an obvious loss in performance. The results indicate that the
      proposed method could be potentially applied in a wide range of doping control,
      clinical, forensic toxicology, food analysis and environmental analyses.

PMID- 29332839
TI  - Magnetic solid-phase extraction based on magnetic multiwalled carbon nanotubes
      for the simultaneous enantiomeric analysis of five beta-blockers in the
      environmental samples by chiral liquid chromatography coupled with tandem mass
      spectrometry.
AB  - In this work, the magnetic multiwalled carbon nanotubes (Mag-MWCNTs) were
      prepared by self-assembly method and characterized by scanning electron
      microscopy, X-ray powder diffraction, energy dispersive X-ray and vibrating
      sample magnetometer. Then, these synthetic Mag-MWCNTs were used as sorbents to
      extract five beta-blockers (atenolol, metoprolol, esmolol, pindolol and
      arotinolol) by magnetic solid-phase extraction. The target analytes adsorbed on
      Mag-MWCNTs were eluted and determined on a chiral alpha-acid glycoprotein column
      coupled with a triple quadrupole mass spectrometry. Eventually, the proposed
      method was applied to the analysis of the enantiomeric composition of the studied
      beta-blockers in three environmental samples, including river water, influent
      wastewater and effluent wastewater. Method detection and quantification limits
      for all enantiomers were in the range of 0.50-1.45 and 1.63-3.75ng/L,
      respectively. Satisfactory recovery (82.9-95.6%), good intra-day precision (RSD
      0.4-10.4%) and inter-day precision (RSD 2.9-7.4%) were also obtained. With
      numerous advantages such as simplicity of operation, rapidity and high enrichment
      factor, the newly developed method has potential to assess the enantioselectivity
      of chiral drugs in ecotoxicity and biodegradation processes, which is also a new
      expanded application of Mag-MWCNTs in the environmental analysis.

PMID- 29332841
TI  - Improved neuron culture using scaffolds made of three-dimensional PDMS micro
      lattices.
AB  - Tissue engineering strives to create functional components of organs with
      different cell types in vitro. One of the challenges is to fabricate scaffolds
      for three-dimensional (3D) cell culture under physiological conditions. Of
      particular interest is the investigation of the morphology and function of the
      central nervous system cultured using such scaffolds. Here, we used an elastomer
      polydimethylsiloxane (PDMS)-to produce lattice-type scaffolds from a
      photolithography-defined template. The photomask with antidot arrays was spin
      coated by a thick layer of resist, and was downward mounted on a rotating stage
      at an angle of 45 degrees . After the exposure was repeated three or more times,
      maintaining the same exposure plan but rotated by the same angle, a photoresist
      was developed to produce a 3D porous template. Afterwards, a pre-polymer mixture
      of PDMS was poured in and cured, followed by a resist etch, resulting in lattice
      type PDMS features. Before cell culture, the PDMS lattices were surface
      functionalized. A culture test was conducted using NIH-3T3 cells and primary
      hippocampal cells from rats, showing homogenous cell infiltration and 3D
      attachment. As expected, a much higher cell number was found in the 3D PDMS
      lattices compared to the 2D culture. We also found a higher neuron-to-astrocyte
      ratio and a higher degree of cell ramification in the 3D culture compared to the
      2D culture due to the change of scaffold topography and the elastic properties of
      the PDMS micro-lattices. Our results demonstrate that the 3D PDMS micro-lattices
      improve the survival and growth of cells, as well as the network formation of
      neurons. We believe that such an enabling technology is useful for research and
      clinical applications, including disease modeling, regenerative medicine, and
      drug discovery/drug cytotoxicity studies.

PMID- 29332842
TI  - Ligand-cascading nano-delivery devices to enable multiscale targeting of anti
      neurodegenerative therapeutics.
AB  - Neurodegenerative diseases are a debilitating set of conditions that affect a
      significant fraction of the world's population, and this fraction is expected to
      increase as the population ages. Many therapeutic strategies have been explored
      to treat the pathological mechanisms of neurodegenerative diseases, but multiple
      sequential hurdles to central nervous system (CNS) delivery, including the blood
      brain barrier (BBB), diseased neuronal membranes, and the organelle barrier, make
      drug delivery challenging and necessitate the use of innovative strategies to
      target and cross each barrier. Advances in drug delivery technology have the
      potential to improve the standard of treatment for neurodegenerative diseases by
      enhancing local drug concentration at the pathologically relevant cells and
      organelles. Furthermore, ligand-cascading nano-delivery devices could address
      these issues by sequentially presenting targeting ligands for crossing each of
      the aforementioned hurdles. In this review, we provide an overview of ligand
      technologies that enable BBB transcytosis, localization to or internalization in
      diseased neuronal cells, and localization at the organelle of interest. We
      summarize recent strategies for sequentially presenting pertinent ligands at each
      hurdle to CNS delivery. These ligand-cascade strategies will enable rational
      design of nano-delivery devices for multiscale targeting of anti
      neurodegenerative therapeutics.

PMID- 29332840
TI  - Examining patterns of multimorbidity, polypharmacy and risk of adverse drug
      reactions in chronic obstructive pulmonary disease: a cross-sectional UK Biobank
      study.
AB  - OBJECTIVE: This study aims: (1) to describe the pattern and extent of
      multimorbidity and polypharmacy in UK Biobank participants with chronic
      obstructive pulmonary disease (COPD) and (2) to identify which comorbidities are
      associated with increased risk of adverse drug reactions (ADRs) resulting from
      polypharmacy. DESIGN: Cross-sectional. SETTING: Community cohort. PARTICIPANTS:
      UK Biobank participants comparing self-reported COPD (n=8317) with no COPD (n=494
      323). OUTCOMES: Multimorbidity (>=4 conditions) and polypharmacy (>=5
      medications) in participants with COPD versus those without. Risk of ADRs (taking
      >=3 medications associated with falls, constipation, urinary retention, central
      nervous system (CNS) depression, bleeding or renal injury) in relation to the
      presence of COPD and individual comorbidities. RESULTS: Multimorbidity was more
      common in participants with COPD than those without (17% vs 4%). Polypharmacy was
      highly prevalent (52% with COPD taking >=5 medications vs 18% in those without
      COPD). Adjusting for age, sex and socioeconomic status, those with COPD were
      significantly more likely than those without to be prescribed >=3 medications
      contributing to falls (OR 2.27, 95% CI 2.13 to 2.42), constipation (OR 3.42, 95%
      CI 3.10 to 3.77), urinary retention (OR 3.38, 95% CI 2.94 to 3.87), CNS
      depression (OR 3.75, 95% CI 3.31 to 4.25), bleeding (OR 4.61, 95% CI 3.35 to
      6.19) and renal injury (OR 2.22, 95% CI 1.86 to 2.62). Concomitant cardiovascular
      disease was associated with the greatest risk of taking >=3 medications
      associated with falls/renal injury. Concomitant mental health conditions were
      most strongly associated with medications linked with CNS depression/urinary
      retention/bleeding. CONCLUSIONS: Multimorbidity is common in COPD and associated
      with high levels of polypharmacy. Co-prescription of drugs with various ADRs is
      common. Future research should examine the effects on healthcare outcomes of co
      prescribing multiple drugs with similar potential ADRs. Clinical guidelines
      should emphasise assessment of multimorbidity and ADR risk.

PMID- 29332843
TI  - Intrinsic electron trapping in amorphous oxide.
AB  - We demonstrate that electron trapping at intrinsic precursor sites is endemic in
      non-glass-forming amorphous oxide films. The energy distributions of trapped
      electron states in ultra-pure prototype amorphous (a)-HfO2 insulator obtained
      from exhaustive photo-depopulation experiments demonstrate electron states in the
      energy range of 2-3 eV below the oxide conduction band. These energy
      distributions are compared to the results of density functional calculations of a
      HfO2 models of realistic density. The experimental results can be explained by
      the presence of intrinsic charge trapping sites formed by under-coordinated Hf
      cations and elongated Hf-O bonds in a-HfO2. These charge trapping states can
      capture up to two electrons, forming polarons and bi-polarons. The corresponding
      trapping sites are different from the dangling-bond type defects responsible for
      trapping in glass-forming oxides, such as SiO2, in that the traps are formed
      without bonds being broken. Furthermore, introduction of hydrogen causes
      formation of somewhat energetically deeper electron traps when a proton is
      immobilized next to the trapped electron bi-polaron. The proposed novel mechanism
      of intrinsic charge trapping in a-HfO2 represents a new paradigm for charge
      trapping in a broad class of non-glass-forming amorphous insulators.

PMID- 29332844
TI  - Understanding carbon nanotube channel formation in the lipid membrane.
AB  - Carbon nanotubes (CNTs) have been considered a prominent nano-channel in cell
      membranes because of their prominent ion-conductance and ion-selectivity,
      offering agents for a biomimetic channel platform. Using a coarse-grained
      molecular dynamics simulation, we clarify a construction mechanism of vertical
      CNT nano-channels in a lipid membrane for a long period, which has been difficult
      to observe in previous CNT-lipid interaction simulations. The result shows that
      both the lipid coating density and length of CNT affect the suitable fabrication
      condition for a vertical and stable CNT channel. Also, simulation elucidated that
      a lipid coating on the surface of the CNT prevents the CNT from burrowing into
      the lipid membrane and the vertical channel is stabilized by the repulsion force
      between the lipids in the coating and membrane. Our study provides an essential
      understanding of how CNTs can form stable and vertical channels in the membrane,
      which is important for designing new types of artificial channels as biosensors
      for bio-fluidic studies.

PMID- 29332845
TI  - N-doped ZnO nanosheets: towards high performance two dimensional catalysts.
AB  - Recently, catalytic activity of atomically thin two dimensional (2D) materials
      has attracted great interest. In this paper, via first principles calculations,
      we show for the first time that N-doped 2D one-atom-thick ZnO nanosheets exhibit
      high catalytic activity towards CO oxidation. A pristine 2D ZnO nanosheet is
      chemically inert and as a result, CO and O2 molecules do not chemically bind on
      the nanosheet. Our calculations predict that the N doping activates the ZnO
      sheet, leading to strong CO and O2 adsorptions. We further show that the CO
      oxidation catalyzed by the N-doped 2D ZnO sheet has a low reaction barrier around
      0.5 eV. Besides high catalytic activity, the N-doped 2D ZnO sheet also
      demonstrates intriguing electronic and magnetic properties. These findings
      provide new opportunities for the future development of high performance 2D
      catalysts.

PMID- 29332846
TI  - Using Concept Mapping to Explore and Engage Parent and Youth Residents of an
      Economically Underserved Minority Community around Children's Asthma.

PMID- 29332847
TI  - Using Concept Mapping to Explore and Engage Parent and Youth Residents of an
      Economically Underserved Minority Community around Children's Asthma.
AB  - BACKGROUND: Asthma continues to disproportionately impact children living in
      economically underserved urban neighborhoods, and contributes to persistent
      racial and economic disparities in health. Furthermore, asthma is often
      exacerbated by the presence of social and environmental factors that are
      prevalent in, and sometimes particular to, these communities. OBJECTIVES: The
      present study uses a community-based participatory research (CBPR) approach to
      explore and define the experience and issues around children's asthma in an
      economically underserved community. These findings will be used to inform the
      design of a community intervention. METHODS: Through a community and academic
      partnership called Healthy Living, Healthy Learning, Healthy Lives (HL3), we
      engaged neighborhood youth and adult residents (N = 21) in a concept mapping
      activity to identify triggers and health care-related factors that influence
      children with asthma. RESULTS: Findings highlight that the most important
      triggers of asthma included indoor and outdoor irritants and allergens, as well
      as violence and fear-related emotions. The most important factors perceived to
      influence the care of asthma included medical relievers such as asthma
      medication, appliances such as a humidifier, and supports for asthma like the
      school nurse. Differences between adults and youth perceptions of factors
      triggering and influencing asthma are highlighted. CONCLUSIONS: Engaging
      community residents as experts provided a deeper understanding of the issues
      around children's asthma in the community, which can contribute to the design of
      a more effective intervention.

PMID- 29332849
TI  - Combined Diabetes Prevention and Disease Self-Management Intervention for
      Nicaraguan Ethnic Minorities: A Pilot Study.
AB  - BACKGROUND: Informed by formative community-based participatory research (CBPR),
      we developed a combined model of diabetes prevention and self-management.
      OBJECTIVES: To assess the feasibility, acceptability, and preliminary efficacy of
      our CBPR-inspired model. METHODS: A mixed methods study was conducted using a pre
      experimental design. The setting was a church-based clinic located on Nicaragua's
      rural Atlantic coast. Miskitos and Creoles with or at risk for diabetes were
      sampled. Preliminary efficacy was assessed with A1C, weight, and quality of life
      (QOL) measures at baseline, 3 months, and 6 months. An open-ended survey assessed
      intervention satisfaction. The 8-week, registered nurse (RN)-led intervention
      emphasized knowledge acquisition and behavioral strategies for dietary, physical
      activity, and medication regimen adherence. Paired t tests were computed to
      assess preliminary efficacy. Content analysis was conducted to assess
      intervention acceptability. RESULTS: A total of 42 participants were enrolled.
      For participants completing follow-up data collection (n = 33), mean A1C improved
      from 8.8% to 8.3% (t = -2.19; p = .04) from baseline to 3 months. Among
      participants with a baseline A1C of greater than 7.5% (n = 24), the mean A1C
      decreased from 9.7% to 9.0% from baseline to 3 months (t = -2.86; p = .01), and
      to 8.7% at 6 months (t = -3.00; p = .01). Nonsignificant weight changes were
      observed. Mental health QOL improved, on average from baseline to 3 months (t =
      2.20; p = .04) and 6 months (t = 4.7; p < .01) for the sample. An increase in
      mean physical health QOL was observed from baseline to 3 months (t = 2.91; p <
      .01). The intervention was found to be acceptable. Study feasibility was good,
      with successful research capacitation and achievement of sampling goals.
      CONCLUSIONS: Findings suggest our novel intervention holds promise for wider
      application to reduce diabetes burden among Nicaraguan ethnic minorities.

PMID- 29332850
TI  - Community Advisory Boards Guiding Engaged Research Efforts within a Clinical
      Translational Sciences Award: Key Contextual Factors Explored.
AB  - BACKGROUND: Engaging stakeholders in research carries the promise of enhancing
      the research relevance, transparency, and speed of getting findings into
      practice. By describing the context and functional aspects of stakeholder groups,
      like those working as community advisory boards (CABs), others can learn from
      these experiences and operationalize their own CABs. Our objective is to describe
      our experiences with diverse CABs affiliated with our community engagement group
      within our institution's Clinical Translational Sciences Award (CTSA). We
      identify key contextual elements that are important to administering CABs.
      METHODS: A group of investigators, staff, and community members engaged in a 6
      month collaboration to describe their experiences of working with six research
      CABs. We identified the key contextual domains that illustrate how CABS are
      developed and sustained. Two lead authors, with experience with CABs and
      identifying contextual domains in other work, led a team of 13 through the
      process. Additionally, we devised a list of key tips to consider when devising
      CABs. RESULTS: The final domains include (1) aligned missions among stakeholders
      (2) resources/support, (3) defined operational processes/shared power, (4) well
      described member roles, and (5) understanding and mitigating challenges. The tips
      are a set of actions that support the domains. CONCLUSIONS: Identifying key
      contextual domains was relatively easy, despite differences in the respective
      CAB's condition of focus, overall mission, or patient demographics represented.
      By contextualizing these five domains, other research and community partners can
      take an informed approach to move forward with CAB planning and engaged research.

PMID- 29332851
TI  - Empirically Derived Lessons Learned about What Makes Peer-Led Exercise Groups
      Flourish.
AB  - BACKGROUND: Physical exercise confers many health benefits, but it is difficult
      to motivate people to exercise. Although community exercise groups may facilitate
      initiation and persistence in an exercise program, reports regarding factors that
      allow such groups to flourish are limited. OBJECTIVES: We performed a prospective
      qualitative evaluation of our experience starting a program of community-based,
      peer-led exercise groups for military veterans to identify important lessons
      learned. METHODS: We synthesized data from structured observations, post
      observation debriefings, and focus groups. Our participants were trained peer
      leaders and exercise group members. Our main outcomes consisted of empirically
      derived lessons learned during the implementation of a peer-led group exercise
      program for veterans at multiple community sites. We collected and analyzed data
      from 40 observation visits (covering 14 sites), 7 transcribed debriefings, and 5
      focus groups. RESULTS: We identified five lessons learned. (1) The camaraderie
      and social aspect of the exercise groups provided motivation for people to stay
      involved. (2) Shared responsibility and commitment to each other by the group
      members was instrumental to success. (3) Regular meeting times encouraged
      participation. (4) Variety, especially getting outdoors, was very popular for
      some groups. (5) Modest involvement of professionals encouraged ongoing
      engagement with the program. CONCLUSIONS: Both social and programmatic issues
      influence implementation of group exercise programs for older, predominantly
      male, veterans. These results should be confirmed in other settings.

PMID- 29332852
TI  - How Co-Developed Are Community and Academic Partnerships?
AB  - BACKGROUND: The world-renowned resources of Johns Hopkins Hospital (JHH) in
      Baltimore, Maryland, stand in marked contrast with the surrounding impoverished
      neighborhoods. Community-based organizations (CBOs) are critical frontline
      responders to residents' needs. Baltimore CONNECT, an academic-community
      partnership, co-developed an intervention to strengthen connections between CBOs
      and between CBOs and the health care system. OBJECTIVES: To understand how
      members of an academic- community partnership define the act of "co-development"
      and share perceptions of barriers, facilitators, and ways to measure it. METHODS:
      We conducted semistructured interviews with 15 community partners, academic
      partners, and external stakeholders. RESULTS: Partners conceptualized co
      development as a fluid and evolving process that is the outcome of shared
      decision making. This exploration revealed nuances within partnership dynamics,
      including motivations for participation, underlying incentives, partnership
      equality, balance of power, and trust and relation building. CONCLUSIONS: We
      present insights that can be used by academic researchers and community leaders
      looking to co-develop interventions to improve health in urban communities
      domestically and internationally.JHH in Baltimore, Maryland, is one of the most
      highly regarded hospitals in the United States. However, its institutional
      resources stand in marked contrast with those available to the impoverished
      neighborhoods that surround it. Many have called for JHH to play a greater role
      in the surrounding community, where it serves as a leading source of health care.

PMID- 29332854
TI  - The Development of a Postpartum Weight Management Intervention for Low-Income
      Women: End-User Perspectives as Groundwork.
AB  - BACKGROUND: Postpartum weight retention (PPWR) leads to increased rates of
      maternal and childhood obesity, especially among low-income families. Literature
      is sparse regarding interventions to address PPWR. OBJECTIVE: To gain practical
      insight into low-income women's preferences and opinions regarding PPWR
      management at a community-based organization (CBO). METHODS: Mixed female focus
      groups composed of CBO staff and clients (n = 17) were asked open-ended questions
      about PPWR and potential intervention components. Systematic analysis of the
      discussions was performed to identify overarching themes. CONCLUSIONS: The tenets
      of community-engaged research state the necessity of developing community-based
      interventions with initial input and partnership with the potential end-users. In
      this study, low-income women were eager to share their thoughts about the
      postpartum period and potential solutions to correct unhealthy weight, thus
      completing a critical step in intervention development. The majority of women
      wanted to manage their weight in the postpartum setting, but needed structure,
      social support, assurance they would not injure themselves or their babies, and
      time saving strategies to do so.

PMID- 29332853
TI  - Implementing the Chronic Care Model for Opioid and Alcohol Use Disorders in
      Primary Care.
AB  - BACKGROUND: Effective treatments for opioid and alcohol use disorders (OAUD) are
      available, yet only a small percentage of those needing treatment receive it.
      OBJECTIVES: This paper describes a collaborative planning and development process
      used by researchers and community providers to apply the chronic care model to
      the delivery of treatment for OAUD in primary care. The goal was to develop and
      implement an intervention that would support the delivery of brief psychotherapy
      and medication-assisted treatment (MAT). METHODS: We used focus groups and
      interviews to identify barriers and facilitators, and organized the results using
      the chronic care model. We then identified implementation strategies, the
      intended organizational changes, and the materials necessary to carry out each
      strategy, and pilot-tested the process. RESULTS AND CONCLUSIONS: We describe the
      methods and outcomes of the collaborative planning and development process, and
      discuss implications of the work for the integration of substance use treatment
      with primary care.

PMID- 29332855
TI  - Yeego Gardening! A Community Garden Intervention to Promote Health on the Navajo
      Nation.
AB  - BACKGROUND: Yeego Gardening! is a community garden intervention to increase
      gardening behavior, increase access to low-cost fruit and vegetables, and
      ultimately increase consumption in Navajo communities. OBJECTIVES: To design a
      theory-based, culturally relevant intervention with three components: a community
      garden, monthly workshops on gardening and healthy eating, and community
      outreach. METHODS: Gardens were constructed and maintained in collaboration with
      community-based organizations in two Navajo communities. Monthly workshops were
      held throughout the growing season and incorporated aspects of Navajo culture and
      opportunities to build confidence and skills in gardening and healthy eating
      behaviors. In addition, program staff attended community events to promote
      gardening and healthy eating. CONCLUSIONS: Community input was essential
      throughout the planning and implementation of the intervention. If effective,
      community gardens may be a way to increase fruit and vegetable availability and
      intake, and ultimately reduce risk of obesity and diabetes.

PMID- 29332856
TI  - Transform Health Arkansas: A Transgender-Led Partnership Engaging Transgender/Non
      Binary Arkansans in Defining Health Research Priorities.
AB  - BACKGROUND: Transgender/non-binary (trans/NB) individuals face major challenges,
      including within health care. OBJECTIVES: Transform Health Arkansas (THA) engaged
      trans/ NB Arkansans in defining their greatest health-related concerns to inform
      responsive, partnered, participatory research. METHODS: The THA partnership
      engaged trans/NB individuals through an interactive, trans/NB-led process in nine
      summits across the state and collected surveys on research interests. Descriptive
      analysis examined respondent characteristics by gender identity, mode of survey
      completion, and most pressing concerns. RESULTS: The summits, attended by 54
      trans/NB and 29 cisgender individuals, received positive evaluations. The top
      five priorities among 140 survey respondents included (1) transition-related
      insurance coverage, (2) access to transition care, (3) education of health care
      providers, (4) public education, and (5) supportive health care systems. The THA
      has also led to trans/NB individuals educating a range of audiences about
      transgender issues. CONCLUSIONS: Next steps include dissemination, identification
      of evidence-based interventions addressing prioritized issues, and joint
      development of a research agenda.

PMID- 29332857
TI  - Food Policy Council Case Study Describing Cross-sector Collaboration for Food
      System Change in a Rural Setting.
AB  - PROBLEM: Food Policy Councils (FPCs) are cross-sector collaborations that bring
      representatives from across the food system together to identify issues,
      coordinate programs, and inform policy. Little is known about how rural FPCs
      operate to influence food access in their communities. PURPOSE: To explore how a
      rural FPC facilitates cross-sector partnerships and influences food system change
      through interviews with eight members of the Adam's County FPC. RESULTS:
      Connections developed through the FPC helped council members work more
      effectively in their home organizations. Four themes were discussed: council
      dynamics and structure; sharing resources, expertise, and information; promoting
      healthy food access through programs; and food policy opportunities and
      challenges. CONCLUSIONS: This case study illustrates connections between FPC
      members in a rural county and identifies how FPCs can facilitate food system
      change in their communities. Improving our understanding of how rural FPCs
      function can help to advance the potential public health impact of councils.

PMID- 29332858
TI  - The effect of thiamine and its metabolites on peripheral neuropathic pain induced
      by cisplatin in rats.
AB  - Thiamine pyrophosphate (TPP) is the active metabolite of thiamine. This study
      aimed to investigate the effects of thiamine and TPP on cisplatin-induced
      peripheral neuropathic pain (PNP). Male albino Wistar type Rattus norvegicus were
      divided into six groups (n=6) that received 2 mg/kg cisplatin (CIS), 25 mg/kg
      thiamine (TM), 2 mg/kg cisplatin+25 mg/kg thiamine (CTM), 25 mg/kg TPP (TPP), 2
      mg/kg cisplatin+25 mg/kg TPP (CTPP), or distilled water (healthy group; HG) for 8
      days intraperitoneally. Analgesic effect was measured with a Basile Algesimeter.
      IL-1beta, malondialdehyde (MDA), total glutathione (tGSH), thiamine, and TPP were
      determined in blood samples. Histopathological examinations were performed on
      removed sciatic nerves. The percent analgesic effects of the CTM and CTPP groups
      were calculated to be 21.3% and 82.9%, respectively. Increased production of IL
      1beta and MDA by cisplatin was inhibited by TPP, while it was not inhibited by
      thiamine. Conversion of thiamine to TPP significantly decreased in the CIS group.
      Histopathological and biochemical investigations demonstrated that hyperalgesia
      and sciatic nerve damage developed in the CIS and CTM groups with low TPP levels.
      These results indicate that cisplatin inhibits the formation of TPP from
      thiamine, leading to severe PNP. This finding suggests that TPP may be more
      beneficial than thiamine for the treatment of cisplatin-induced PNP.

PMID- 29332859
TI  - Grading fatty liver by ultrasound time-domain radiofrequency signal analysis: an
      in vivo study of rats.
AB  - This study aimed to assess the severity of fatty liver (FL) by analyzing
      ultrasound radiofrequency (RF) signals in rats. One hundred and twenty rats (72
      in the FL group and 48 in the control group) were used for this purpose.
      Histological results were the golden standard: 42 cases had normal livers (N), 30
      cases had mild FL (L1), 25 cases had moderate FL (L2), 13 cases presented with
      severe FL (L3), and 10 cases were excluded from the study. Four RF parameters
      (Mean, Mean/SD ratio [MSR], skewness [SK], and kurtosis [KU] were extracted.
      Univariate analysis, spearman correlation analysis, and stepwise regression
      analysis were used to select the most powerful predictors. Receiver operating
      characteristic (ROC) analysis was used to compare the diagnostic efficacy of
      single indexes with a combined index (Y) expressed by a regression equation.
      Mean, MSR, SK, and KU were significantly correlated with FL grades (r=0.71,
      P<0.001; r=0.81, P<0.001; r=-0.79, P<0.001; and r=-0.74, P<0.001). The regression
      equation was Y=-4.48 + 3.20 * 10-2X1 + 3.15X2 (P<0.001), where Y=hepatic
      steatosis grade, X1 =Mean, and X2 =MSR. ROC analysis showed that the curve areas
      of the combined index (Y) were superior to simple indexes (Mean, MSR, SK, and KU)
      in evaluating hepatic steatosis grade, and they were 0.95 (L>=L1), 0.98 (L>=L2),
      and 0.99 (L>=L3). Ultrasound radiofrequency signal quantitative technology was a
      new, noninvasive, and promising sonography-based approach for the assessment of
      FL.

PMID- 29332860
TI  - Impact of the Great East Japan Earthquake on Body Mass Index, Weight, and Height
      of Infants and Toddlers: An Infant Survey.
AB  - BACKGROUND: The body mass index (BMI) of preschool children from 4 years of age
      through primary school has increased since the Great East Japan Earthquake, but
      that of children aged under 3 years has not been studied. This study evaluated
      how the anthropometrics of younger children changed following the earthquake.
      METHODS: Height and weight data of children living in northeast Japan were
      collected from 3-, 6-, 18-, and 42-month child health examinations. We compared
      the changes in BMI, weight, and height among infants affected by the earthquake
      between their 3- and 6-month health examinations, toddlers affected at 21-30
      months of age (affected groups), and children who experienced the earthquake
      after their 42-month child health examination (unaffected group). A multilevel
      model was used to calculate the BMI at corresponding ages and to adjust for the
      actual age at the 3-month health examination, health examination interval, and
      gestational age. RESULTS: We recruited 8,479 boys and 8,218 girls living in
      Fukushima, Miyagi, and Iwate Prefectures. In the infants affected between their 3
      and 6-month health examinations in Fukushima, the change in BMI at 42 months of
      age was greater than among the unaffected children. In the toddlers affected at
      21-30 months of age in Fukushima, the change in BMI was greater, but changes in
      weight and height were less. CONCLUSIONS: Affected infants and toddlers in
      Fukushima suggested some growth disturbances and early adiposity rebound, which
      can cause obesity. The future growth of children affected by disasters should be
      followed carefully.

PMID- 29332861
TI  - Epicardial Fat Thickness and Bone Mineral Content: The Healthy Twin Study in
      Korea.
AB  - BACKGROUND: The conventional concept of positive association between general
      obesity and bone health was challenged in recent studies reporting the different
      effects of specific fat deposition on bone health. In the present study, we
      investigated the association between epicardial fat and bone health. METHODS: We
      measured echocardiographic epicardial fat thickness (EFT) and bone mineral
      content (BMC) in a twin-family cohort of Koreans (n = 1,198; 525 men, 460 pre-
      and 213 post-menopausal women). A total 121 pairs of monozygotic twin (MZ) and
      404 pairs of dizygotic twin and sibling pairs (DZ/Sib) were included. RESULTS:
      EFT was positively associated with BMC in total, as well as in three subgroups
      (beta = 0.107, 0.076, and 0.058 for men, pre-, and post-menopausal women,
      respectively). The positive association between EFT and BMC remained for DZ/Sib
      difference analysis, but was absent for MZ comparisons. The positive association
      between BMI and BMC was consistent for DZ/Sib and MZ difference analysis. After
      adjusting for the effect of general obesity via BMI, the association between BMC
      and EFT was statistically non-significant (beta = 0.020, 0.000, and -0.009 for
      men, pre-, and post-menopausal women, respectively). CONCLUSION: Our findings do
      not support epicardial fat's beneficial effects on bone health, whereas general
      adiposity has an osteotropic effect. The association between EFT and BMC is
      through common genetic component factors.

PMID- 29332862
TI  - Using relaxation techniques to improve sleep during naps.
AB  - Insufficient sleep is a common occurrence in occupational settings (e.g. doctors,
      drivers, soldiers). The resulting sleep debt can lead to daytime sleepiness,
      fatigue, mood disorder, and cognitive deficits as well as altered vascular,
      immune and inflammatory responses. Short daytime naps have been shown to be
      effective at counteracting negative outcomes related to sleep debt with positive
      effects on daytime sleepiness and performance after a normal or restricted night
      of sleep in laboratory settings. However, the environmental settings in the
      workplace and the emotional state of workers are generally not conducive to
      beneficial effects. Here, we tested whether relaxation techniques (RT) involving
      hypnosis might increase total sleep time (TST) and/or deepen sleep. In this
      study, eleven volunteers (aged 37-52) took six early-afternoon naps (30 min) in
      their occupational workplace, under two different conditions: control 'Naps' or
      'Naps + RT' with a within-subjects design. Our results demonstrate that adding RT
      to naps changes sleep architecture, with a significant increase in the TST,
      mostly due to N2 sleep stage (and N3, to a lesser extent). Therefore, the
      deepening of short naps with RT involving hypnosis might be a successful non
      pharmacological way to extend sleep duration and to deepen sleep in occupational
      settings.

PMID- 29332863
TI  - Lipid Parameters are Independently Associated with Cardio-Ankle Vascular Index
      (CAVI) in Healthy Japanese Subjects.
AB  - AIM: To investigate the associations of conventional lipid parameters with
      arterial stiffness assessed by cardio-ankle vascular index (CAVI). METHODS: A
      retrospective cross-sectional study was conducted in 23,257 healthy Japanese
      subjects (12,729 men and 10,528 women, aged 47.1+/-12.5 years, body mass index
      (BMI) 22.9+/-3.4 kg/m2) who underwent health screening between 2004 and 2006 in
      Japan. RESULTS: Male subjects had significantly higher BMI, CAVI and
      triglycerides (TG), and lower high-density lipoprotein cholesterol (HDL-C)
      compared to female subjects. After adjusting for confounders, including gender,
      age, systolic blood pressure and BMI identified by multiple regression analysis,
      adjusted CAVI was lower in normolipidemic than in dyslipidemic subjects. Among
      dyslipidemic subjects, those with hypertriglyceridemia had higher adjusted CAVI.
      A trend test detected linear relations between adjusted CAVI and all the
      conventional lipid parameters throughout the entire range of serum levels. After
      adjusting for confounders, logistic regression models showed that all lipid
      parameters contributed independently to high CAVI (>=90th percentile). Receiver
      operating-characteristic analysis determined reliable cut-off values of 93 mg/dl
      for TG (area under the curve, AUC= 0.735), 114 mg/dl for low-density lipoprotein
      cholesterol (AUC=0.614) and 63 mg/dl for HDL-C (AUC=0.728) in predicting high
      CAVI. These cut-off values were confirmed to independently predict high CAVI in a
      bivariate logistic regression model. CONCLUSION: The present study demonstrated
      independent contribution of conventional lipid parameters to CAVI, indicating a
      possible association of lipid parameters with early vascular damage.

PMID- 29332864
TI  - Associations of periparturient plasma biochemical parameters, endometrial
      leukocyte esterase and myeloperoxidase, and bacterial detection with clinical and
      subclinical endometritis in postpartum dairy cows.
AB  - This study was aimed at demonstrating associations between peripheral biochemical
      parameters, endometrial leukocyte esterase (LE) and myeloperoxidase (MPO), and
      bacterial detection with the degree of endometrial inflammation, and determining
      the best time postpartum for diagnosing endometritis to predict subsequent
      fertility in dairy cows. Plasma albumin, blood urea nitrogen (BUN), total
      cholesterol (T-cho), NEFA, and BHBA concentrations were analyzed in 43 Holstein
      cows at 3, 5 and 7 weeks postpartum (W3, W5 and W7). Endometrial samples were
      collected at W3, W5 and W7 to examine LE and MPO activities, bacterial detection
      rates, and PMN% profiles. The 43 cows were divided into healthy (HE), subclinical
      endometritis (SE), and clinical endometritis (CE) groups, classified differently
      at W3, W5 and W7 based on the definitions of SE and CE for each of the three
      weeks pp. LE level had an association with PMN% in all weeks pp (P<0.05). Albumin
      and BUN levels had weak negative associations with endometrial PMN% at W3.
      Pathogenic bacterial detection rates were higher in the cows with endometritis at
      W3 and W5. Conception rate at first artificial insemination tended to be lower
      (P=0.057) in the cows diagnosed with endometritis at W3 than in the healthy cows.
      In conclusion, associations were found between endometrial LE and endometritis,
      but not for MPO and endometritis. Diagnosing endometritis in W3 may be the best
      moment to predict subsequent fertility.

PMID- 29332866
TI  - Impact of Stent Type on the Long-Term Prognosis of Patients With Vasospastic
      Angina - Can We Judge a Stent Just by Its Cover?

PMID- 29332865
TI  - Fibrillar architecture at three different sites of the bovine superficial digital
      flexor tendon.
AB  - Superficial digital flexor tendon (SDFT) of the bovine hindlimb originates from
      the caudolateral aspect of the distal femur and finally inserts onto the plantar
      aspect of the middle phalanges. In the present study, morphology and morphometry
      of the bovine SDFT at the muscle-tendon junction (MTJ), middle metatarsus (mM)
      and tendon-bone interface (TBI) were investigated. Cross-sectional morphology at
      the three regions of SDFT were oval, semioval and ring-formed, respectively.
      Significant difference in cross-sectional area was found only between MTJ-mM and
      mM-TBI (P<0.05). Functional compression and friction from the adjacent structures
      could be the most potential interactions affecting such appearances. Morphometric
      data of tenocyte number, water content, and glycosaminoglycan (GAG) length and
      angle were found increasing in the proximodistal direction, except the fibril
      diameter and collagen fibril index (CFI). Statistical analyzes could reveal
      significant differences in average number of tenocytes (P<0.0001), CFI (between
      MTJ-mM and MTJ-TBI, P<0.05), water content (between MTJ-TBI, P<0.05), length of
      GAG chains (between MTJ-TBI, P<0.05), and angle of GAG chains (P<0.0001),
      respectively. The fibrillar characteristics at the three different areas,
      including fibril diameter distribution and interfibrillar distance, existed in
      conforming to the tensional axes in situ. In addition, length and angle of GAG
      chains were relevant to moving directions of the collagen fibrils.

PMID- 29332867
TI  - ?

PMID- 29332868
TI  - [Azacitidine treatment for acute myeloid leukemia with myelodysplasia-related
      changes during peritoneal dialysis].
AB  - Azacitidine (AZA) is useful for the treatment of myelodysplastic syndrome;
      however, there are a few case reports involving patients receiving hemodialysis
      and no case reports involving patients receiving peritoneal dialysis. We describe
      a patient with acute myeloid leukemia with myelodysplasia-related changes (AML
      MRC) receiving peritoneal dialysis who was treated with AZA. Peritoneal dialysis
      was initiated for an 85-year-old man with chronic renal failure in April 2014. In
      February 2015, peripheral blood analysis showed pancytopenia and bone marrow
      examination revealed excess of myeloblasts and dysplasia of trilineage cells. He
      was diagnosed with AML-MRC and treated with AZA because of being elderly and
      suffering from chronic renal failure. He achieved transfusion independence after
      1 course and hematological remission after 3 courses of AZA treatment, without
      severe side effects. This case suggests that AZA is an effective therapeutic
      option for patients with AML-MRC receiving peritoneal dialysis.

PMID- 29332869
TI  - [Disseminated fusariosis in patients with acute leukemia: a retrospective
      analysis of three cases].
AB  - We report three cases of fusariosis that occurred during the treatment of acute
      leukemia, during the past 5 years at our institution. Case 1: A 70-year-old male
      with relapsed and refractory acute lymphoblastic leukemia (ALL) developed fever
      and multiple nodular lesions in both the lungs. Blood culture that was
      subsequently obtained revealed Fusarium species. Treatment with liposomal
      amphotericin B (L-AMB) was ineffective, and the condition of the patient
      deteriorated rapidly leading to death. Case 2: A 28-year-old male with T-ALL
      developed echthyma gangrenosum (EG) ulcers on the scrotum during conditioning for
      transplantation. Antifungal therapy with L-AMB was ineffective, and later,
      itraconazole and micafungin (MCFG) were introduced. However, the engraftment was
      not achieved, and the patient died on day 27. Microbiological examination of EG
      samples collected on day 13 revealed infection by Fusarium species post mortem.
      Case 3: A 50-year-old male with blast crisis of chronic myeloid leukemia
      developed EG primarily on the trunk during chemotherapy. The patient died without
      any response to L-AMB and MCFG. A culture obtained from EG on day 19 yielded
      Fusarium species, post mortem. The prognosis of fusariosis is extremely poor.
      However, skin lesions such as EG may assist in the early diagnosis of the
      disseminated disease.

PMID- 29332871
TI  - [Successful treatment of secondary graft failure with donor lymphocyte infusion
      in a post-allogeneic stem cell transplant acute myeloid leukemia patient].
AB  - Here we report a case of secondary graft failure that was effectively treated
      with donor lymphocyte infusion (DLI). A 64-year-old female patient with acute
      myeloid leukemia obtained partial remission with azacitidine therapy and
      subsequently underwent unrelated allogeneic bone marrow transplantation (BMT).
      After confirming successful engraftment and achieving complete remission with
      incomplete blood count recovery, she was subsequently followed up at an
      outpatient clinic. A routine test performed by day 110 after BMT revealed the
      presence of pancytopenia. A bone marrow aspirate did not reveal any evidence of
      disease relapse or hemophagocytic syndrome but demonstrated hematopoietic
      insufficiency. Donor chimerism also declined over time; thus, the patient was
      diagnosed with secondary graft failure. Supportive treatment, including
      granulocyte-colony stimulating factor and blood transfusion, failed to improve
      the blood parameters. Because the patient refused a second BMT, we performed DLI
      on day 147 after BMT (CD3+ cells: 1.0*107/kg, single dose). Consequently, the
      blood cell count improved promptly and dramatically without adverse events.
      Following this, we discussed the case and analyzed the related literature.

PMID- 29332870
TI  - [Autologous peripheral blood stem cell transplantation for double-refractory
      myeloma with K-RAS and N-RAS mutations].
AB  - The prognosis of multiple myeloma (MM) has been improved due to the introduction
      of novel agents like proteasome inhibitors and immunomodulatory drugs (IMiDs).
      However, some cases are refractory to the use of novel agents, and the prognosis
      of such cases is poor. A 53-year-old male was diagnosed with MM and categorized
      as follows: Bence-Jones protein lambda type MM, Durie-Salmon IIIA, international
      staging system (ISS) stage II, and revised ISS stage II. Mutations in K-RAS and
      IGH/FGFR3 translocation were detected at diagnosis. His tumor was refractory to
      seven therapeutic regimens including bortezomib, IMiDs (lenalidomide,
      thalidomide, pomalidomide), conventional chemotherapy, and radiation therapy. N
      RAS mutations, CKS1B gains, and C-MYC split signals were detected after
      treatment. We performed high-dose melphalan/autologous stem cell transplantation
      (HD-MEL/ASCT) as a salvage therapy and achieved very good partial response. The
      correlation between K-RAS mutations and poor prognosis or between N-RAS mutations
      and reduced sensitivity to bortezomib is reported. However, RAS mutations are
      reported as a favorable factor for HD-MEL/ASCT. In general, mutations of both the
      K-RAS and N-RAS are known to be mutually exclusive. This rare MM case has
      mutations in both K-RAS and N-RAS, and the possible relevance of these mutations
      to both the refractoriness to novel therapies and sensitivity to HD-MEL/ASCT is
      suggested.

PMID- 29332872
TI  - [Successful treatment of large granular lymphocytic leukemia accompanied by
      refractory anemia with alemtuzumab].
AB  - A 39-year-old man with anemia presented at our hospital in November 2011.
      Peripheral blood analysis revealed lymphocytosis with a large granular lymphocyte
      (LGL) count of 2,272/ul, with CD3+, CD4-, CD8+, CD56-, TCR-alphabeta+; Southern
      blotting analysis revealed clonal TCR Cbeta 1 gene rearrangement, leading to the
      diagnosis of T-LGL leukemia. In June 2012, the patient was administered with
      cyclophosphamide as an initial treatment because he developed transfusion
      dependent anemia. His anemia improved, and the treatment was discontinued in
      March 2013. However, anemia recurred in March 2014. The administration of
      cyclophosphamide was resumed; however, it was subsequently replaced with
      cyclosporine because of the risk of secondary cancer due to the long-term use of
      cyclophosphamide. However, his anemia did not improve. Further, the patient was
      administered with prednisone, methotrexate, and pentostatin; however, the
      transfusion-dependent state persisted with the cumulative transfusion of 186 RBC
      units until March 2016. After CD52 expression on the surface of LGL cells was
      confirmed, treatment with alemtuzumab, which is a monoclonal antibody against
      CD52, was initiated in April 2016 and the dose was gradually increased from 3 mg
      to 30 mg thrice per week. The patient's anemia began to improve 1 week after
      initiating alemtuzumab treatment, and he became transfusion-independent in the
      second week. Although alemtuzumab treatment was discontinued at the fifth week on
      the basis of a positive test result for CMV antigenemia, the result consequently
      became negative after ganciclovir treatment. To date, the patient's hemoglobin
      level has been maintained at approximately 12 g/dl without any treatment. Herein
      we reported the case of a patient having LGL leukemia with refractory anemia that
      was successfully treated using alemtuzumab.

PMID- 29332873
TI  - [Durable remission attained by long-term brentuximab vedotin administration in a
      relapsed post-allogeneic bone marrow transplant Hodgkin lymphoma patient].
AB  - The prognosis for relapsed Hodgkin lymphoma after allogeneic hematopoietic cell
      transplantation (HSCT) is poor, partly because of limited treatment options. Here
      we present a case of a Hodgkin lymphoma patient who relapsed after allogeneic
      HSCT but remains in complete remission (CR) at 38 months from the start of
      extended brentuximab vedotin (BV) dosing. A 33-year-old man with refractory and
      relapsed nodular sclerosis classical Hodgkin lymphoma who underwent previous
      treatments, including adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD)
      ; seven combination regimens; and autologous HSCT, prior to allogeneic HSCT
      achieved CR after three cycles of BV. BV was continued for 26 cycles and then
      discontinued because of a neurogenic bladder. The other adverse effects were mild
      paresthesia in the fingers, mild dysgeusia, and fatigue. The patient still
      remains in CR at 38 months from the start of BV. Thus, extended BV dosing may be
      a treatment option for relapsed and refractory Hodgkin lymphoma after allogeneic
      HSCT.

PMID- 29332874
TI  - [Myelodysplastic syndrome with refractory hemorrhage due to reduced platelet
      aggregation activity].
AB  - A 75-year-old woman suffered a cat bite 10 months after myelodysplastic syndrome
      (MDS) diagnosis. She visited our hospital because the internal bleeding of the
      wound did not improve. Although the wound was treated, the bleeding did not stop.
      She was hospitalized for emergency medical treatment because the bleeding volume
      exceeded 200 ml. Although her platelet count was normal, the platelet function
      test showed a decrease in collagen and arachidonic acid aggregation. After
      platelet transfusion, her bleeding stopped. Patients with MDS may potentially
      have platelet dysfunction. In the case of bleeding without thrombocytopenia, a
      platelet function test should be performed and treatment intervention, such as
      platelet transfusion, should be considered.

PMID- 29332875
TI  - [Recurrent multiple lung lesions synchronizing with the disease activity of
      multiple myeloma].
AB  - A 68-year-old male patient, who was diagnosed with MGUS (IgG-lambda) 11 years
      ago, was referred to our hospital because of a progressing pancytopenia. He was
      diagnosed with multiple myeloma (MM) and was hospitalized because of fever and
      pneumonia. Although empiric antibiotic and antifungal therapies were promptly
      initiated, his pneumonia worsened. Chest CT images revealed diffuse interstitial
      pneumonia. Although bortezomib/dexamethasone therapy was initiated as a treatment
      for MM and pneumonia, he showed little response. His pneumonia worsened and
      progressed to acute respiratory distress syndrome. Using mPSL (500 mg/day),
      sivelestat, and MM treatment switching to lenalidomide/dexamethasone (Rd), his
      respiratory status and CT findings rapidly improved. He received Rd therapy as an
      outpatient; however, after the completion of six cycles of therapy, his MM
      progressed, with a recurrence of pneumonia and high fever again. The onset of
      pneumonia was closely associated with MM progression. His pneumonia improved by
      treatment with mPSL half-pulse and MM treatment switching to carfilzomib/Rd. In
      the present study, we report the case of a patient with myeloma, who presented
      with multiple interstitial pneumonia, resulting in respiratory failure twice in
      concordance with myeloma progression.

PMID- 29332876
TI  - [Primary breast diffuse large B-cell lymphoma developing subsequent to
      estramustine therapy for prostate cancer].
AB  - An 85-year-old male presented with 1-year history of a right breast mass. Needle
      biopsy of the mass revealed diffuse proliferation of large lymphoid cells that
      were positive for CD20, BCL2, BCL6, and MUM1 and negative for CD5, CD10, MYC, and
      EBER. The patient was diagnosed as having diffuse large B-cell lymphoma, a type
      of primary breast lymphoma (PBL). Sex hormone imbalance, which causes conditions
      such as gynecomastia, is associated with PBL development in males. Estramustine
      is a nitrogen mustard moiety linked to estradiol. For 5 years, the patient
      underwent estramustine therapy for treating prostate cancer. Our case suggests an
      important role of estrogen in PBL development.

PMID- 29332877
TI  - [Overview].

PMID- 29332878
TI  - [Impact of HLA mismatch on transplant outcomes].
AB  - Human leukocyte antigen (HLA) mismatch increases the risk of severe graft-versus
      host disease (GVHD) and transplant-related mortality. However, the variety of
      stem cell sources such as cord blood units or the improvements in GVHD
      prophylaxis makes the interpretation of HLA mismatch more complex. In unrelated
      transplantation, the locus of HLA mismatch has a great impact on the donor
      candidate selection, whereas in related transplantation, it has an impact on the
      intensity of GVHD prophylaxis because donor availability is limited. Anti
      thymocyte globulin and post-transplant cyclophosphamide are attractive GVHD
      prophylactic agents to reduce the risk of immune-associated complications in HLA
      mismatched transplantations. HLA mismatch has a reduced impact in adult cord
      blood transplantation. In this review article, the impact of HLA mismatch based
      on graft sources is discussed.

PMID- 29332879
TI  - [Progresses in pretransplant conditioning strategies].
AB  - Reduction of pretransplant conditioning intensity since the late 1990s has
      resulted in an increased incidence of relapse, although the number of
      transplantations has dramatically increased. In the 2000s, pretransplant
      conditioning was intensified again using drugs with less non-hematological
      toxicity. For myeloid malignancies, intravenous busulfan (ivBu), which has lesser
      toxicity than its oral formulation, was introduced. Its myeloablative dose can be
      safely administered to many patients, including the elderly. Fludarabine-ivBu
      combination is reported to be comparable or even better than conventional
      myeloablative conditioning regimens, such as Bu-Cy or TBI-Cy, for those 50 years
      and older. The cumulative incidence of early NRM post-transplant in patients in
      remission was more or less comparable to those undergoing the Seattle regimen
      consisting of Flu+TBI 2 Gy. Incorporating novel drugs into conditioning regimens
      may further reduce toxicity, particularly for patients not in remission.

PMID- 29332880
TI  - [Impact of genetic polymorphisms on post-transplant complications].
AB  - Genetic association studies are now widely applied to various medical conditions
      and abnormalities. Unfortunately, it remains challenging to conduct such studies
      in cases that require hematopoietic stem cell transplantation (HSCT) because
      candidate patients usually have a complicated clinical background. In this field,
      a uniform cohort and well-designed protocol are critical to increasing the
      effectiveness of genetic association analyses, and parameters such as pre
      conditioning regimen, donor source, graft versus host disease and its
      prophylaxis, and disease status need to be considered. Our studies thus far have
      revealed that focusing on the relationship between drug metabolism-associated
      genes and drug-induced complications after HSCT could often offset the
      complicated clinical background. Thus, here we describe a genetic association
      study focused on complications after HSCT.

PMID- 29332881
TI  - [Mesenchymal stem cells for treatment of graft-versus-host disease].
AB  - Steroid-refractory graft-versus-host disease (SR-GVHD) is one of the most
      important complication post allogeneic hematopoietic stem cell transplantation.
      Mesenchymal stem cells (MSCs) possess characteristic immunomodulatory features
      which are beneficial in the salvage treatment for SR-GVHD. Following the first
      case report in 2004, numerous clinical trials have shown encouraging results with
      MSC infusions for treating SR-GVHD. In Japan, two clinical trials have achieved
      favorable results, and subsequently in September 2015, MSC infusion became the
      first approved allogeneic cell therapy for SR-GVHD. Currently, MSCs are available
      at limited institutes, and all patients infused with MSCs have been registered in
      the post marketing survey. Based on the results of this survey, the establishment
      of guidelines for the proper use of MSCs is anticipated. Moreover, several groups
      have reported the efficacy of MSCs for chronic GVHD or GVHD prophylaxis. In the
      present review, current issues regarding the use of MSCs in the management of
      GVHD are summarized.

PMID- 29332883
TI  - ?

PMID- 29332882
TI  - [Role of long-term follow-up in management of late-onset post-hematopoietic stem
      cell transplant complications].
AB  - As the number of long-term survivors after allogeneic hematopoietic stem cell
      transplantation (HSCT) has increased owing to advances in transplantation and
      supportive care techniques, the health and welfare of these survivors have come
      into focus. However, they are still at risks for various complications, including
      chronic graft-versus-host disease, infectious diseases, and secondary cancers
      even in the late period, which can not only interfere with the patient's quality
      of life (QOL) but also lead to death. The importance of long-term follow-up
      (LTFU) and management have been recently recognized, and nationwide systems to
      promote LTFU care in patients receiving HSCT, such as medical fee revision,
      publication of a LTFU guideline unique to Japan, and preparation of patient
      pocketbook, is under consideration. The number of medical facilities at LTFU
      outpatient clinic is also increasing; therefore, an optimal comprehensive support
      system may be established sooner or later. However, self-management by patients
      is essential to overcome late complications as well as to improve QOL after HSCT.
      Healthcare professionals should collaborate and continue to make the greatest
      possible efforts to educate patients regarding the risks of late complications
      and their prevention.

PMID- 29332884
TI  - ?

PMID- 29332885
TI  - ?

PMID- 29332886
TI  - Improved systemic delivery of insulin by condensed drug loading in a dimpled
      suppository.
AB  - The development of peptide therapeutics owing to the advances in biotechnology
      has overcome some unmet medical needs; however, the route of administration is
      still limited to injections. Systemic delivery of insulin via an enteral route
      remains a great challenge due to its instability and low mucosal permeability. In
      this study, we investigated the effect of drug condensation in a suppository on
      the efficacy of insulin after rectal administration. Suppositories with dimples
      are prepared by a mold method using a hard fat (Suppocire(r) AM). Insulin or
      fluorescein isothiocyanate-dextran (molecular weight: 3,000-5,000) (FD4) as a
      model of a hydrophilic macromolecule was loaded in the dimples, and sealed with
      other lipids with different melting points. The in vitro release test showed that
      the time to 50% drug release depends on the melting point of the lipid for
      sealing but not on the number of dimples. The suppositories with one-, or three
      dimple containing insulin and caprylocaproyl macrogol-8 glyceride (Labrasol(r))
      were administered to rats at 0.5 U/head. The reduction in plasma glucose level
      was more significant for the one-dimple-type suppository than for the three
      dimple-type although the one-dimple-type suppository contained less amount of
      Labrasol by one-third compared to the three-dimple-type. These results suggest
      that condensation of an insulin dose in a limited surface area of a suppository
      improves systemic availability via the rectal route with a reduced amount of an
      absorption enhancer.

PMID- 29332887
TI  - Both triazolyl ester of ketorolac (15K) and YM155 inhibit the embryonic
      angiogenesis in ovo (fertilized eggs) via their common PAK1-survivin/VEGF
      signaling pathway.
AB  - 15 K is 1,2, 3-triazolyl ester of ketorolac, an old pain-killer, that blocks PAK1
      by its R-form and inhibits COX-2 by its S-form. Mainly due to a robust increase
      in cell-permeability, 15K is over 500 times more potent than ketorolac in both
      anti-cancer and anti-PAK1 activities in cell culture with IC50 around 24 nM.
      However, 15K has no anti-AKT activity. Angiogenesis requires at least the kinase
      PAK1, and perhaps the kinase AKT as well, and is essential for a robust growth of
      solid tumors. Thus, in this study, we examined the potential antiangiogenic
      activity of 15K both in ovo and cell culture, prior to its in vivo (xenograft)
      anti-cancer activity test. The IC50 of 15K against the embryonic angiogenesis in
      ovo in CAM (chorioallantoic membrane) assay is around 1 nmol/egg. Surprizingly,
      however, 15K failed to inhibit the tube formation of HUVECs (human umbilical vein
      endothelial cells) in cell culture even at high as 150 MUM. In an attempt to
      solve this mystery, we tested both in ovo as well as HUVECs-based anti-angiogenic
      activity of a potent survivin-suppressor called YM155, which blocks PAK1, in
      addition to AKT. YM155 is slightly more potent than 15K in CAM assay with IC50
      around 0.5 nmol/egg, and apparenty inhibits the tube formation of HUVECs with
      IC50 around 18 nM. According to a few previous findings with the direct PAK1
      inhibitor frondoside A (FRA), the tube formation of HUVECs depends solely on
      PAK1. Thus, the failure of 15K to affect their tube formation is most likely due
      to their drug (15K)-resistance. Furthermore, unlike FRA, YM155 killed HUVECs with
      IC50 around 18 nM, clearly indicating that AKT is essential for survival of
      HUVECs, instead of their tube formation.

PMID- 29332888
TI  - Potential of Piper betle extracts on inhibition of oral pathogens.
AB  - In the present study, antimicrobial activity of Piper betle crude ethanol extract
      against 4 strains of oral pathogens; Candida albicans DMST 8684, C. albicans DMST
      5815, Streptococcus gordonii DMST 38731 and Streptococcus mutans DMST 18777 was
      compared with other medicinal plants. P. betle showed the strongest antimicrobial
      activity against all tested strains. Fractionated extracts of P. betle using
      hexane, ethyl acetate, and ethanol, respectively, were subjected to antimicrobial
      assay. The result revealed that the fractionated extract from ethyl acetate (F
      EtOAc) possessed the strongest antimicrobial activity against all tested strains.
      Its inhibition zones against those pathogens were 23.00 +/- 0.00, 24.33 +/- 0.58,
      12.50 +/- 0.70 and 11.00 +/- 0.00 mm, respectively and its minimum inhibitory
      concentrations were 0.50, 1.00, 0.50 and 1.00 mg/mL, respectively. Interestingly,
      the minimum concentration to completely kill those pathogens was the same for all
      strains and found to be 2.00 mg/mL. Killing kinetic study revealed that the
      activity of F-EtOAc was dose dependent. HPLC chromatograms of P. betle extracts
      were compared with its antimicrobial activity. An obvious peak at a retention
      time of 4.11 min was found to be a major component of F-EtOAc whereas it was a
      minor compound in the other extracts. This peak was considered to be an active
      compound of P. betle as it was consistent with the antimicrobial activity of F
      EtOAc, the most potential extract against the tested pathogens. It is suggested
      that F-EtOAc is a promising extract of P. betle for inhibition of oral pathogens.
      Separation and structure elucidation of the active compound of this extract will
      be further investigated.

PMID- 29332889
TI  - Effects of Caesalpinia sappan on pathogenic bacteria causing dental caries and
      gingivitis.
AB  - The present study explores antimicrobial activities of Caesalpinia sappan
      extracts against three strains of oral pathogenic bacteria; Streptococcus mutans
      DMST9567 (Smu9), Streptococcus mutans DMST41283 (Smu4), and Streptococcus
      intermedius DMST42700 (Si). Ethanol crude extract of C. sappan (Cs-EtOH) was
      firstly compared to that of other medicinal plants using disc diffusion method.
      Cs-EtOH showed significantly higher effective inhibition against all tested
      strains than other extracts and 0.12% chlorhexidine with the inhibition zone of
      17.5 +/- 0.5, 18.5 +/- 0.0, and 17.0 +/- 0.0 mm against Smu9, Smu4, and Si,
      respectively. Three fractionated extracts of C. sappan using hexane, ethyl
      acetate, and ethanol, respectively, were further investigated. The fractionated
      extract from ethanol (F-EtOH) presented the strongest activities with the minimum
      bactericidal concentration (MBC) of 125-250 ug/mL. Killing kinetics of F-EtOH was
      depended on the bacterial species and the concentration of F-EtOH. Two-fold MBC
      of F-EtOH could kill all tested strains within 12 h whereas its 4-fold MBC showed
      killing effect against Si within 6 h. Separation of F-EtOH by column
      chromatography using chloroform/methanol mixture as an eluent yielded 11
      fractions (F1-F11). The fingerprints of these fractions by high-performance
      liquid chromatography at 280 nm revealed that F-EtOH consisted of at least 5
      compounds. F6 possessed the significantly highest antimicrobial activity among 11
      fractions, however less than F-EtOH. It is considered that F-EtOH is the
      promising extract of C. sappan for inhibiting oral pathogenic bacteria and
      appropriate as natural antiseptic for further develop of oral hygiene products.

PMID- 29332890
TI  - In vitro oral epithelium cytotoxicity and in vivo inflammatory inducing effects
      of anesthetic rice gel.
AB  - In vitro cytotoxicity of lidocaine hydrochloride (LH) and prilocaine
      hydrochloride (PH) to oral epithelial cells, isolated from tissue specimens of
      healthy volunteers, were evaluated. Cell vitality after treating with 1-20%
      anesthetic solutions for 5 and 30 min was investigated using F-actin and 4',6
      diamidino-2-phenylindole staining technique and observed by fluorescence
      microscopy. Vitality rate of more than 90% was found in all anesthetic groups at
      both durations whereas no survived cell was found in a positive control group
      (sodium dodecyl sulfate). Lactate dehydrogenase (LDH) assay was performed to
      confirm the safety of both anesthetic solutions. Cell culture medium after
      treating with LH or PH for 5 and 30 min were collected and analyzed using
      commercial kits. The results showed no significant difference between the test
      groups and negative control group (untreated culture) with low LDH levels. In
      vivo inflammatory inducing effect of 5, 10, 20% LH or PH loaded rice gels was
      investigated in healthy volunteers. Tumor necrosis factor alpha (TNF-alpha) in
      gingival cervicular fluid was determined by ELISA technique. It was found that
      the expression of TNF-alpha was not different from the baseline. The expression
      of this inflammatory mediator caused by the commercial gel was higher than those
      of both anesthetic rice gels. It might be due to the effects of other excipients
      in the formulation of the commercial product. It is concluded that LH or PH
      possess no cytotoxicity to oral epithelium and the developed rice gel base and LH
      and PH rice gels do not induce inflammatory effect to oral tissues.

PMID- 29332891
TI  - Protective effects of Phaseolus vulgaris lectin against viral infection in
      Drosophila.
AB  - Phytohemagglutinin (PHA) isolated from the family of Phaseolus vulgaris beans is
      a promising agent against viral infection; however, it has not yet been
      demonstrated in vivo. We herein investigated this issue using Drosophila as a
      host. Adult flies were fed lectin approximately 12 h before they were subjected
      to a systemic viral infection. After a fatal infection with Drosophila C virus,
      death was delayed and survival was longer in flies fed PHA-P, a mixture of L4,
      L3E1, and L2E2, than in control unfed flies. We then examined PHA-L4,
      anticipating subunit L as the active form, and confirmed the protective effects
      of this lectin at markedly lower concentrations than PHA-P. In both experiments,
      lectin feeding reduced the viral load prior to the onset of fly death.
      Furthermore, we found a dramatic increase in the levels of the mRNAs of
      phagocytosis receptors in flies after feeding with PHA-L4 while a change in the
      levels of the mRNAs of antimicrobial peptides was marginal. We concluded that P.
      vulgaris PHA protects Drosophila against viral infection by augmenting the level
      of host immunity.

PMID- 29332892
TI  - Digital PCR for determination of cytochrome P450 2D6 and sulfotransferase 1A1
      gene copy number variations.
AB  - CYP2D6 and SULT1A1 occasionally show copy number variations (CNVs), with a larger
      number generally indicating greater enzymic activity. However, those variations
      are difficult to calculate using standard methods. With digital PCR, a recently
      introduced method for CNV analysis, DNA molecules are subjected to limited
      dilution and separated into nano-scale droplets prior to a PCR assay. Absolute
      quantitation of copy number can then be performed with high accuracy and
      sensitivity by determining the number of droplets showing an amplified signal for
      the target gene. This is the first report of analyses of CYP2D6 and SULT1A1 CNVs
      using a digital PCR method with blood sample from Japanese subject. Primers and
      probes were synthesized for the target and reference genes, and copy number
      calculation was performed using a QX200 Droplet Digital PCR System. Our results
      showed that the copy numbers in CYP2D6*5 hetero, non-CNV, and CYP2D6xN subjects
      were 1, 2, and 3 to 4, respectively. In addition, in non-CNV and multiplication
      subjects, the number of copies for SULT1A1 was 2 and 3 to 6, respectively. We
      found that the present digital PCR method was useful as well as accurate. In the
      future, a combined genotyping, allele distinction, and copy number calculation
      technique will be helpful for analysis of enzymic activity.

PMID- 29332893
TI  - Do scleroderma patients look young?: Evaluation by using facial imaging system.
AB  - These days various collagen supplements have widely been marketed. However, it
      has not been scientifically proved whether increasing collagen can actually
      prevent skin aging. Systemic sclerosis (SSc) is an autoimmune disease that is
      characterized by thickening of the skin caused by accumulation of collagen. In
      this study, we tried to evaluate facial skin characteristics and skin aging of
      SSc patients by using digital imaging system. As the result, the severity of
      wrinkles, texture and pores were significantly lower in SSc patients than control
      subjects. Among them, wrinkles showed better correlation with skin thickness
      score. Therefore, increased amount of collagen in scleroderma skin may directly
      affect wrinkles. In conclusion, attempt on collagen induction itself is
      reasonable and effective strategy in order to keep young appearance, although
      oral collagen supplementation may not directly reach to the skin.

PMID- 29332894
TI  - Bullous dermatosis on legs of elderly: A new clinical entity?
AB  - A lot of diseases occur on the skin of elderly persons. We report four elderly
      cases of bullous dermatosis that did not meet various differential diagnoses.
      Japanese, heart failure, atrophic skin and leg edema probably due to aging, as
      well as flaccid or tense bullae localized in legs were the common factors to our
      patients. Such conditions may be increased in coming aging society. Accordingly,
      it is worth regarding such symptom as the new clinical entity, which may comfort
      patients with similar condition and attract further attention.

PMID- 29332895
TI  - Breakthrough mucormycosis after voriconazole use in a case of invasive fungal
      rhinosinusitis due to Curvularia lunata.
AB  - Invasive fungal rhinosinusitis (FRS) is a potentially fatal illness requiring
      early diagnosis and aggressive treatment with surgery and antifungals. We report
      a case of chronic FRS in a recently diagnosed diabetic individual due to
      Curvularia lunata. Imaging revealed extension into the right orbit and right
      basifrontal lobe. This was further complicated by development of nosocomial
      mucormycosis which was attributed to voriconazole therapy. The patient responded
      well to debridement and amphotericin B based therapy. To our knowledge, there are
      no reported cases of invasive FRS due to Curvularia lunata. Also, breakthrough
      mucormycosis on voriconazole therapy is rarely seen in non-malignancy, non
      transplant settings. The possibility of rare fungal infections (community and
      nosocomial) should be entertained in developing settings where fungal spores are
      ubiquitous.

PMID- 29332896
TI  - Iron, Hematological Parameters and Blood Plasma Lipid Profile in Vitamin D
      Supplemented and Non-Supplemented Young Soccer Players Subjected to High
      Intensity Interval Training.
AB  - Vitamin D deficiency has been associated with increased risk for cardiovascular
      disease and anemia. Vitamin D-related changes in lipid profile have been studied
      extensively but the relationship between vitamin D and lipid metabolism is not
      completely understood. As both vitamin D and intermittent training may
      potentially affect iron and lipid metabolism, the aim of the study was to
      evaluate whether a daily supplementation of vitamin D can modulate the response
      of hematological and lipid parameters to high-intensity interval training (HIIT)
      in soccer players. Thirty-six young elite junior soccer players were included in
      the placebo-controlled, double-blind study. Participants were non-randomly
      allocated into either a supplemented group (SG, n=20, HIIT and 5,000 IU of
      vitamin D daily) or placebo group (PG, n=16, HIIT and sunflower oil).
      Hematological parameters were ascertained before and after the 8-wk training. The
      change score (post- and pre-training difference) was calculated for each
      individual and the mean change score (MCS) was compared between SG and PG using
      the t test and analysis of covariance. There were no differences between SG and
      PG at baseline. The red and white cell count, hemoglobin, hematocrit, MCHC,
      ferritin, and HDL-cholesterol changed significantly over the 8-wk HIIT. However,
      no significant differences in MCS were observed between SG and PG for any
      variable. A daily vitamin D supplement did not have any impact on alteration in
      hematological or lipid parameters in young soccer players in the course of high
      intensity interval training.

PMID- 29332897
TI  - Effect of Lithium on the Mechanism of Glucose Transport in Skeletal Muscles.
AB  - While lithium is known to stimulate glucose transport into skeletal muscle, the
      mechanisms of the increased glucose transport by lithium in skeletal muscle are
      not well defined yet. We excised epitrochlearis muscles from male Wistar rats and
      measured the transport rates of a glucose analog into lithium-, insulin-, and
      muscular contraction-stimulated skeletal muscle tissue and we also analyzed the
      levels of cell surface glucose transport 4 using a photolabeling and multicolor
      immunofluorescence method. In addition, we generated a cell line that stably
      expresses myc-tagged GLUT4 to measure the rates of GLUT4 internalization and
      externalization. Lithium significantly increased 2-DG glucose transport rate in
      skeletal muscles; however, it was significantly lower than the stimulation
      induced by the maximum concentration of insulin or tetanic contraction. But co
      treatment of lithium with insulin or tetanic contraction increased glucose
      transport rate by ~200% more than lithium alone. When skeletal muscle tissues
      were treated with lithium, insulin, and muscular contraction, the levels of cell
      surface GLUT4 protein contents were increased similarly by ~6-fold compared with
      the basal levels. When insulin or lithium stimuli were maintained, the rate of
      GLUT4myc internalization was significantly lower, and lithium was found to
      suppress the internalization of GLUT4myc more strongly. The lithium-induced
      increase in glucose uptake of skeletal muscles appears to increase in cell
      surface GLUT4 levels caused by decreased internalization of GLUT4. It is
      concluded that co-treatment of lithium with insulin and muscular contraction had
      a synergistic effect on glucose transport rate in skeletal muscle.

PMID- 29332898
TI  - Effect of Dietary Protein Levels on Protein Nutritional Status in Growing Female
      Rats Kept under Constant Darkness.
AB  - The purpose of this study was to clarify the effects of dietary protein levels on
      protein nutritional status in rats kept under constant darkness. Thirty-six 4-wk
      old female rats (F344 strain) were divided into six groups. Each group was given
      a diet with one of three different protein levels and kept under normal light and
      dark cycles (7:00-19:00 light period/19:00-7:00 dark period, N group) or under
      constant darkness (D group) for 4 wk. The protein levels of the diets were 10%,
      20%, and 30% casein. The six groups are referred to as the N10%, N20%, N30%,
      D10%, D20%, and D30% groups. Body weight gain was low in the D groups, and that
      in the D30% group was much lower than that in the N30% group. The D30% group
      retained less nitrogen than the N30% group. As for the amount of urinary nitrogen
      excreted every 4 h, the values for the D-groups were higher than those for the N
      groups in the 11:00-15:00 periods, and that for the D30% group was higher than
      that for the N30% group in the 15:00-19:00 periods, which means that protein
      catabolism was higher in the D30% group. It was shown that when rats kept under
      constant darkness were fed a high-protein diet for 4 wk, their nitrogen retention
      decreased and their protein nutritional state dropped.

PMID- 29332899
TI  - Relationship between Dietary Protein or Essential Amino Acid Intake and Training
      Induced Muscle Hypertrophy among Older Individuals.
AB  - Dietary protein intake is critical for maintaining an optimal muscle mass,
      especially among older individuals. Although protein supplementation during
      resistance training (RT) has been shown to further augment training-induced
      muscle mass in older individuals, the impact of daily variations in protein
      intake on training-induced muscle mass has not been explored thus far. Therefore,
      this study aimed to investigate the relationship between the dietary protein and
      amino acid intake and RT-induced muscle hypertrophy among older individuals. Ten
      healthy older men (n=10; mean age=69+/-2 y; body weight (BW)=61.5+/-2.2 kg;
      height=1.65+/-0.02 m) participated in progressive RT performed 3 times/wk for 12
      wk. Body composition (using DXA) and nutritional assessments (using a 3-d dietary
      record) were performed before and after the training period. Leg lean mass (LLM)
      increased significantly (15.0+/-0.8 vs. 15.4+/-0.8 kg, p<0.05) after RT, with no
      change in dietary nutrient intake. The average dietary protein intake was 1.62+/
      0.11 g/kg BW/d, while essential amino acids was 600+/-51 mg/kg BW/d. Although the
      correlation between the increase in LLM and dietary protein intake was not
      significant, a significant correlation was found between the increase in LLM and
      dietary essential amino acid (EAA) intake. Furthermore, there were significant
      correlations between the increase in LLM and protein as well as EAA (especially
      leucine) intake at breakfast among subjects with suboptimal protein intake
      (p<0.05). Our study findings indicate that dietary protein as well as EAA intake
      may be significant contributing factors in muscle hypertrophic response during RT
      among healthy older men.

PMID- 29332900
TI  - Changes in Thyroid Hormone Are Not Involved in Regulating Brain Protein Synthesis
      in Adults Rats Fed Ornithine.
AB  - Brain protein synthesis and the plasma concentration of growth hormone (GH) are
      sensitive to dietary ornithine. However, dietary ornithine does not increase
      brain protein synthesis in hypophysectomized rats. Because hypophysectomy may
      decrease the secretion of thyroid stimulated hormone (TSH), we assessed whether
      the regulation of brain protein synthesis was mediated by changes in the plasma
      concentrations of thyroid hormone and ghrelin in the 6-propyl-2-thiouracil (PTU,
      thyroid inhibitor)-treated or control adult rats fed ornithine. The four
      experimental groups consisted of PTU-treated and control (24-wk-old) male rats
      given 0% or 0.7% ornithine-HCl added to a 20% casein diet. The plasma
      concentrations of GH and ghrelin, and the fractional rates of protein synthesis
      and RNA activity [g protein synthesized/(g RNA*d)] in the brains were
      significantly increased after treatment with the 20% casein + 0.7% ornithine
      compared with the 20% casein diet alone in both the PTU-treated and control
      groups. Ornithine supplementation to the basal diet did not affect the plasma
      concentration of T3. The RNA concentration (mg RNA/g protein) was not related to
      the fractional rate of protein synthesis in the brain regions. The results
      suggest that dietary ornithine likely increases the rate of brain protein
      synthesis in control and PTU-treated rats, and that the ornithine-induced
      increase in the GH concentration may stimulate mainly brain protein synthesis via
      ghrelin. RNA activity is at least partly related to the fractional rate of brain
      protein synthesis.

PMID- 29332901
TI  - The Relationship between Habitual Dietary Intake and Gut Microbiota in Young
      Japanese Women.
AB  - Recent studies have shown that dietary content affects the health of the host by
      changing the gut microbiota. However, little is known about the association of
      microbiota composition with habitual diet in Japanese people. Here, we aimed to
      clarify the relationship between the fecal microbiota and habitual dietary intake
      of micronutrients, macronutrients and food groups in healthy young Japanese
      women. Analysis of fecal microbiota was performed by the terminal restriction
      fragment length polymorphism (T-RFLP) method, and a dietary survey was conducted
      over three consecutive days using a weighed food record method. T-RFLP pattern
      analysis divided the subjects into two clusters, where cluster A group had a high
      relative abundance of Bacteroides and Clostridium cluster IV, and cluster B group
      had a high relative abundance of Bifidobacterium and Lactobacillales. Cluster A
      group also had lower intakes of iron and vitamin K and higher intakes of
      mushrooms and snacks than cluster B group. Analysis of Spearman rank correlations
      found several significant relationships between fecal microbiota and intake of
      nutrients and food groups. Bifidobacterium was correlated with iron intake, and
      Clostridium cluster XI was negatively correlated with intakes of cholesterol and
      eggs. These results suggest that dietary habits may strongly affect
      Bifidobacterium, Bacteroides and Clostridium abundance in the gut microbiota of
      young Japanese women. This is the first study to show relationships between fecal
      microbiota and habitual dietary intake in Japanese people. Accumulation of
      results from similar studies will help to elucidate the relationships between
      dietary intake and diseases in Japanese people.

PMID- 29332902
TI  - Effects of Enzymatically Synthesized Glycogen and Exercise on Abdominal Fat
      Accumulation in High-Fat Diet-Fed Mice.
AB  - The combination of diet and exercise is the first choice for the treatment of
      obesity and metabolic syndrome. We previously reported that enzymatically
      synthesized glycogen (ESG) suppresses abdominal fat accumulation in obese rats.
      However, the effect of the combination of ESG and exercise on abdominal fat
      accumulation has not yet been investigated. Our goal in this study was therefore
      to evaluate the effects of dietary ESG and its combination with exercise on
      abdominal fat accumulation in high-fat diet (HFD)-fed mice. Male ICR mice were
      assigned to four groups: HFD, HFD containing 20% ESG, HFD with exercise, HFD
      containing 20% ESG with exercise. Treadmill exercise was performed for 3 wk (25
      m/min, 30 min/d, 3 d/wk) after 5-d adaption to running at that speed. Both ESG
      and exercise significantly reduced the weights of abdominal adipose tissues. In
      addition, the combination of ESG and exercise significantly suppressed abdominal
      fat accumulation, suggesting that ESG and exercise showed an additive effect.
      Exercise significantly increased the mRNA levels of lipid metabolism-related
      genes such as lipoprotein lipase, peroxisome proliferator-activated receptor
      delta; factor-delta (PPARdelta), carnitin palmitoyltransferase b, adipose
      triglyceride lipase (ATGL), and uncoupling protein-3 in the gastrocnemius muscle.
      On the other hand, dietary ESG significantly decreased the mRNA levels of
      PPARdelta and ATGL in the gastrocnemius muscle. These results suggest that the
      combined treatment of ESG and exercise effectively suppresses abdominal fat
      accumulation in HFD-fed mice by different mechanisms.

PMID- 29332903
TI  - Galactose Is the Limiting Factor for the Browning or Discoloration of Cheese
      during Storage.
AB  - The browning or discoloration of cheese is often observed during long-time
      ripening or aging. In the present study, we identified galactose as a limiting
      factor for the browning, and clarified the involvement of the Maillard reaction
      for the discoloration. A precursor of browning of Cheddar cheese was isolated by
      procedures of solvent extraction and chromatography. D-Galactose and D-lactose
      were identified as a precursor of browning of Cheddar cheese A and B,
      respectively. Cheddar cheese (A, B, and C), sugar-added cheese, and nine kinds of
      retail cheese were stored at 4 to 70oC for 0 to 10 d, before the L*-, a*-, and b*
      values and sugar contents of each sample were measured. Cheese to which galactose
      was added turned brown more intensively during storage than the non-added control
      and the other sugar-added cheese. The more galactose was added, the more
      intensive the browning of the cheese appeared. The decrease in galactose
      correlated with the DeltaL*-, Deltaa*-, Deltab*-, and DeltaE-values indicating
      the browning or discoloration of cheese samples. The decrease in sugars of nine
      kinds of retail cheese during storage also correlated with the DeltaL*-, Deltaa*
      , and DeltaE-values of these cheese samples. These results clearly indicate that
      sugars, especially galactose, in cheese are an important factor for the browning
      of cheese during storage. In general, a high amount of amino acids, peptides, and
      proteins exists in ripe or mature cheese. Therefore, sugars, especially
      galactose, were considered to be the limiting factor for the Maillard reaction
      causing the browning of ripe or mature cheese during storage.

PMID- 29332904
TI  - Detection of Fucoidan in Urine after Oral Intake of Traditional Japanese Seaweed,
      Okinawa mozuku (Cladosiphon okamuranus Tokida).
AB  - Seaweed has been considered an indigestible food. Fucoidan, which is found
      abundantly in seaweed, especially in Cladosiphon okamuranus (Okinawa mozuku), has
      a high molecular weight and has been long believed to be hardly absorbed in the
      human digestive system due to a lack of certain digestive enzymes. We previously
      reported that fucoidan can be detected in serum and urine after oral intake of
      purified fucoidan in humans and rats. However, it is unclear whether the fucoidan
      in mozuku can be absorbed after digestion of mozuku. Therefore, we attempted to
      detect fucoidan in urine before and after mozuku intake. We determined the
      fucoidan concentration in urine after oral intake of Okinawa mozuku and urinary
      fucoidan was detected in several volunteers. In conclusion, these results suggest
      that fucoidan in mozuku can be absorbed after ingestion of mozuku.

PMID- 29332905
TI  - Egg White Hydrolysate Improves Glucose Tolerance in Type-2 Diabetic NSY Mice.
AB  - We have previously reported that chicken egg white (EW) and low-allergenic EW
      hydrolysate (EWH) suppressed ectopic fat accumulation and improved serum glucose
      and insulin levels. In this study, the dietary effects of EW and EWH on glucose
      tolerance were investigated in different ways to clarify the effect of EW and EWH
      on intestinal glucose absorption. Type 2 diabetic Nagoya-Shibata-Yasuda mice were
      divided into four groups: a low-fat and low-sucrose casein-based diet group (NL);
      high-fat and high-sucrose (HFS) casein-based diet group (NH); HFS EW-based diet
      group (NE); and HFS EWH-based diet group (NEH). Mice were fed their respective
      diets for 8 wk. At the end of the 6th and 7th week, an oral glucose tolerance
      test (OGTT) and insulin tolerance test (ITT) were respectively conducted in
      experiment A. At the end of the 7th week, an intraperitoneal glucose tolerance
      test (ipGTT) was conducted in experiment B. In experiment A, the plasma glucose
      level was suppressed in the NE group during both OGTT and ITT, and suppressed in
      the NEH group during OGTT, but not during ITT. In experiment B, the plasma
      glucose level was similarly suppressed in the NEH group during ipGTT, but the
      suppressive effect was weakened compared to OGTT. Plasma insulin level was lower
      in the NE and NEH groups in both experiments. Fecal triacylglycerol excretion was
      increased in the NE and NEH groups in experiment A and liver triacylglycerol
      content was suppressed in the NE group in experiment B. These findings suggested
      that in addition to improving fat metabolism, EWH improves glucose tolerance via
      mechanisms related and unrelated to small intestinal function.

PMID- 29332906
TI  - A Nuclear Factor Involved in Transcriptional Regulation of the AREBP Gene.
AB  - The AICAR responsive element binding protein (AREBP) suppresses transcription of
      the gluconeogenic enzyme genes in response to AICAR treatment. Moreover,
      overexpression of AREBP also suppresses gluconeogenic gene expressions in
      animals, indicating that AREBP plays an important role in gluconeogenesis.
      Through a combination of systematic analyses of the AREBP gene promoter and
      assays for DNA-protein interaction, we identified a nuclear factor involved in
      tissue-specific expression of AREBP. By targeting this nuclear factor,
      pharmacological or nutraceutical induction of AREBP gene expression is expected
      to reduce blood glucose levels in patient with insulin resistance.

PMID- 29332907
TI  - Patients' Characteristics and Clinical Course of Hypertrophic Cardiomyopathy in a
      Regional Japanese Cohort - Results From Kochi RYOMA Study.
AB  - BACKGROUND: There have been few studies on the clinical course of hypertrophic
      cardiomyopathy (HCM) in a community-based patient cohort in Japan.Methods and
      Results:In 2004, we established a cardiomyopathy registration network in Kochi
      Prefecture (the Kochi RYOMA study) that consisted of 9 hospitals, and finally,
      293 patients with HCM were followed. The ages at registration and at diagnosis
      were 63+/-14 and 56+/-16 years, respectively, and 197 patients (67%) were male.
      HCM-related deaths occurred in 23 patients during a mean follow-up period of
      6.1+/-3.2 years. The HCM-related 5-year survival rate was 94%. In addition, a
      total of 77 cardiovascular events that were clinically severe occurred in 70
      patients, and the HCM-related 5-year event-free rate was 80%. Multivariate Cox
      proportional hazards model analysis showed that the presence of NYHA class III at
      registration was a significant predictor of HCM-related deaths and that the
      presence of atrial fibrillation, lower fractional shortening and presence of left
      ventricular outflow tract obstruction in addition to NYHA class III were
      significant predictors of cardiovascular events. CONCLUSIONS: In our unselected
      registry in an aged Japanese community, HCM mortality was favorable, but one
      fifth of the patients commonly suffered from HCM-related adverse cardiovascular
      events during the 5-year follow-up period. Careful management of HCM patients is
      needed, particularly for those with the above-mentioned clinical determinants.

PMID- 29332908
TI  - Optical Coherence Tomography Guidance in Management of Acute Coronary Syndrome
      Caused by Plaque Erosion.
AB  - For several decades, most physicians have believed that acute coronary syndrome
      (ACS) is caused by coronary thrombosis resulting from rupture of vulnerable
      plaque characterized by a thin fibrous cap overlying a large necrotic core and
      massive inflammatory cell infiltration. However, nearly one-third of ACS cases
      are caused by plaque erosion characterized by intact fibrous cap, less or absent
      necrotic core, less inflammation, and large lumen. Because of the limitations of
      current imaging modalities, including angiography and intravascular ultrasound,
      the importance of plaque erosion as a cause of acute coronary events is less well
      known. Optical coherence tomography (OCT) as an emerging modality with extremely
      high resolution is the only intravascular imaging modality available for
      identification of plaque erosion in vivo, which provides new insight into the
      mechanism of ACS. More importantly, the introduction of OCT to clinical practice
      enables us to differentiate the patients with ACS caused by plaque erosion from
      those caused by plaque rupture, thereby providing precise and personalized
      therapy based on the different underlying mechanisms. We systematically review
      the morphological characteristics of plaque erosion identified by OCT and its
      implications for the management of ACS.

PMID- 29332909
TI  - Type 2 Myocardial Infarction - An Evolving Entity.
AB  - Type 2 myocardial infarction (T2MI) refers to myocardial necrosis caused by an
      imbalance in myocardial oxygen supply and demand and in the absence of acute
      coronary thrombosis. Despite growing recognition of this entity, there remains
      little understanding of the pathophysiology and uncertainty over the diagnostic
      criteria for this subtype of MI. Alarmingly, recent studies suggest that a
      diagnosis of T2MI pertains a prognosis similar to, if not worse than, type 1 MI.
      With increasing clinical use of high-sensitivity cardiac troponin assays, the
      frequency of recognition of T2MI is expected to increase. Yet, there remains a
      scarcity of prospective studies examining this cohort of patients, let alone
      randomized clinical trials identifying optimum treatment strategies. Further
      evaluation of the prevalence, pathophysiology and management of this patient
      cohort is warranted by the scientific community.

PMID- 29332910
TI  - Successful Infant Pneumonectomy with Unilateral Pulmonary Artery Occlusion Test.
AB  - The use of unilateral pulmonary artery occlusion (UPAO) test for the preoperative
      evaluation of pneumonectomy was reported in adult patients. On the contrary, in
      infants, no strategies have yet been recommended to predict hemodynamics after
      pneumonectomy, nor has use of the UPAO test been reported. We describe the first
      case of infant with abnormal pulmonary circulation in whom successful
      pneumonectomy was performed after preoperative evaluation using UPAO test. Right
      pneumonectomy was planned for an 8-month-old girl, because of decreased right
      pulmonary function, high risk of pneumothorax, and impaired left lung expansion
      due to overexpansion caused by severe left bronchial stenosis and bronchomalacia.
      However, she had also prolonged pulmonary hypertension and there was difficulty
      in accurate echocardiographic evaluation of its severity due to concomitant left
      pulmonary artery stenosis. Furthermore, contrast-enhanced computer tomography
      suggested a certain degree of right pulmonary venous flow, discordant with the
      result showing scarce right pulmonary flow in perfusion scintigraphy. Predicting
      postoperative hemodynamic changes was therefore considered difficult. To evaluate
      these concerns, we performed cardiac catheterization and UPAO test to simulate
      postoperative hemodynamics. Pulmonary arteriography showed decreased but
      significant right pulmonary arterial and venous flows. Measurements including
      pulmonary artery pressure and cardiac index showed no marked changes after
      occlusion. Based on UPAO test results, the operation was successfully performed
      and hemodynamics remained stable postoperatively. The UPAO test may be useful for
      infants with cardiopulmonary impairment to evaluate the tolerability of
      pneumonectomy.

PMID- 29332911
TI  - Impact of Continuous Administration of Tolvaptan on Preventing Medium-Term
      Worsening Renal Function and Long-Term Adverse Events in Heart Failure Patients
      with Chronic Kidney Disease.
AB  - Tolvaptan (TLV) has an inhibiting effect for worsening renal function (WRF) in
      acute decompensated heart failure (HF) patients. However, there are limited data
      regarding the effect of continuous TLV administration on medium-term WRF.This was
      a retrospective observational study in hospitalized HF patients with chronic
      kidney disease (CKD). TLV was administered to those patients with fluid retention
      despite standard HF therapy. We compared 34 patients treated with TLV (TLV group)
      to 33 patients treated with conventional HF therapy with high-dose loop diuretics
      (furosemide >= 40 mg) (Loop group). Clinical outcomes, including the incidence of
      medium-term WRF, defined as increase of serum creatinine > 0.3 mg/dL, at 6 months
      after discharge and adverse events rate, were evaluated.Baseline patient
      characteristics were not different between the TLV and Loop group. The TLV group
      consisted of less frequent use of loop diuretics and carperitide compared with
      the Loop group. The incidence of medium-term WRF was significantly lower in the
      TLV group than in the Loop group (3.2% versus 31.0%, P = 0.002). Multivariate
      logistic analysis showed that the TLV non-user was an independent predictor of
      medium-term WRF. Kaplan-Meier analysis revealed that the long-term event-free
      survival was significantly higher in the TLV group (log-rank P = 0.01).Continuous
      administration of TLV may reduce the risk of medium-term WRF, resulting
      possibility in improvement of long-term adverse outcomes in HF patients with CKD.

PMID- 29332913
TI  - Early Extubation in the Operating Room after Congenital Open-Heart Surgery.
AB  - Early extubation in the operating room after congenital open-heart surgery is
      feasible, but extubation in the intensive care unit after the operation remains
      common practice at many institutions. The purpose of this study was to evaluate
      retrospectively the adequacy of our early-extubation strategy and exclusion
      criteria through analysis based on the Risk Adjustment in Congenital Heart
      Surgery method (RACHS-1).This retrospective analysis included 359 cases requiring
      cardiopulmonary bypass (male, 195; female, 164; weight > 3.0 kg; aged 1 month to
      18 years). Neonates and preoperatively intubated patients were excluded. Other
      exclusion criteria included severe preoperative pulmonary hypertension, high-dose
      catecholamine requirement after cardiopulmonary bypass, delayed sternal closure,
      laryngomalacia, serious bleeding, and delayed awakening. The early-extubation
      rates were compared between age groups and RACHS-1 classes.Overall, 83% of cases
      (298/359) were extubated in the operating room, classified by RACHS-1 categories
      as follows: 1, 59/59 (100%); 2, 164/200 (84%); 3, 61/78 (78%); and 4-6, 10/22
      (45%). The early extubation rate in categories 1-3 (86%, 288/337) was
      significantly higher than for categories 4-6 (45.5%, 10/22) (P < 0.001). Because
      they met one of the exclusion criteria, 61 patients (17%) were not extubated in
      the operating room. Eight patients (2.7%) required re-intubation after early
      extubation in the operating room, and longer operation time was significantly
      associated with re-intubation (P < 0.001).Extubation in the operating room after
      congenital open-heart surgery was feasible based on our criteria, especially for
      patients in the low RACHS-1 categories, and involves a very low rate of re
      intubation.

PMID- 29332912
TI  - Impairment of Iodine-123-Metaiodobenzylguanidine (123I-MIBG) Uptake in Patients
      with Pulmonary Artery Hypertension.
AB  - According to recent studies, lung uptake of iodine-123-metaiodobenzylguanidine
      (123I-MIBG) is impaired in many lung diseases and low lung uptake of 123I-MIBG
      suggests endothelial dysfunction of the pulmonary artery. 123I-MIBG scintigraphy
      in patients with pulmonary hypertension (PH) has not yet been clinically
      evaluated. We hypothesized that the lung uptake of 123I-MIBG is reduced in
      patients with PH and differs among PH subtypes. The purpose of the present study
      was to analyze the lung uptake of 123I-MIBG in patients with PH and compare it
      with the data obtained by echocardiography or right heart catheterization. 123I
      MIBG scintigraphy was performed in 286 consecutive patients from 2003 to 2014. We
      enrolled 21 patients with PH and 8 control patients. The 21 patients with PH were
      categorized into those with pulmonary artery hypertension (PAH, n = 12) and those
      with chronic thromboembolic pulmonary hypertension (CTEPH, n = 9). The mean
      pulmonary artery pressure was not significantly different between patients with
      CTEPH and PAH (37.7 +/- 6.8 versus 32.3 +/- 5.3 mmHg respectively; P = 0.054).
      There were no significant differences in any other hemodynamic parameters between
      the two groups. The lung uptake of 123I-MIBG in PAH patients (early image: 1.54
      +/- 0.18, delayed image: 1.41 +/- 0.16) was significantly lower than that of
      CTEPH patients (early image: 2.17 +/- 0.25, P < 0.0001; delayed image: 1.99 +/-
      0.20, P = 0.0001, adjusted for age and World Health Organization classification)
      and controls (early image: 2.32 +/- 0.27, P = 0.0007; delayed image: 1.92 +/-
      0.19, P = 0.0007). In conclusion, we found for the first time that the lung
      uptake of 123I-MIBG in patients with PAH is lower than that in patients with
      CTEPH and controls.

PMID- 29332914
TI  - Long-Term Clinical Outcomes after Treatment with Excimer Laser Coronary
      Atherectomy for In-Stent Restenosis of Drug-Eluting Stent.
AB  - Excimer laser coronary atherectomy (ELCA) has been used for the treatment of
      complex percutaneous coronary intervention (PCI) such as in-stent restenosis
      (ISR). However, little information was provided about the clinical outcomes after
      treatment with ELCA for ISR of drug-eluting stents (DES). This study aimed to
      investigate the long-term clinical outcomes after PCI with ELCA for ISR of DES.A
      total of 81 consecutive patients with 87 lesions who underwent PCI for ISR of DES
      were included. Patients were classified into a PCI with ELCA group (23 patients
      with 24 lesions) and a PCI without ELCA group (58 patients with 63 lesions). The
      major adverse cardiac events (MACE) were evaluated. The mean duration of clinical
      follow-up was 29.8 +/- 11.6 months. The incidences of diffuse restenosis and
      AHA/ACC type B2 or C lesion in the PCI with ELCA group were higher than in the
      PCI without ELCA group. Quantitative coronary angiography showed the acute
      luminal gain in the PCI with ELCA group was greater than in the PCI without ELCA
      group (1.64 +/- 0.48 mm versus 1.26 +/- 0.42 mm, P < 0.001). There were no
      significant differences in all-cause death, myocardial infarction, or target
      lesion revascularization between the 2 groups. Multivariate analysis due to a Cox
      proportional-hazards model showed that multivessel disease was an independent
      predictor of MACE (hazard ratio 3.05, 95% confidence interval 1.22 to 7.61, P =
      0.02). ELCA was effective as an atherectomy device for lumen enlargement and
      optimal lesion preparation. Even though ELCA was used for ISR of DES in
      significantly more complex lesions, the long-term clinical outcomes were
      favorable and similar.

PMID- 29332915
TI  - Calcified Amorphous Tumor-Induced Acute Cerebral Infarction.
AB  - We report the case of a 38-year-old woman who was admitted for acute cerebral
      infarction linked to a cardiac calcified amorphous tumor (CAT) and related mitral
      annular calcification (MAC). The cardiac mass was removed, and mitral valve
      replacement surgery was performed. Pathological examination revealed an amorphous
      accumulation of degenerating material within both lesions, indicating that build
      up of calcium along the mitral annulus and subsequent rupture of the fibrotic
      tissue may be involved in the initiation and progression of CAT.

PMID- 29332916
TI  - MiR-135a Promotes Inflammatory Responses of Vascular Smooth Muscle Cells From
      db/db Mice via Downregulation of FOXO1.
AB  - It has been shown that microRNAs (miRNAs) greatly affect the functions of
      vascular smooth muscle cells (VSMC), but the effects of mRNAs under diabetic
      conditions remain unclear.Using a model of diabetic db/db mice, we studied the
      functions of microRNA-135a (miR-135a) during VSMC dysfunction.Compared to control
      WT mice, miR-135a expression in VSMC was significantly increased while the level
      of forkhead box O1 (FOXO1) protein decreased significantly. After transfecting
      miR-135a mimics into VSMC, the expression of FOXO1 was decreased, while
      cyclooxygenase-2 (COX-2) and monocyte chemoattractant protein-1 (MCP-1)
      expression levels were increased, thus promoting the interaction between
      monocytes and WT VSMC. On the other hand, transfection of an miR-135a inhibitor
      reversed the activated interaction between monocytes and db/db VSMC. The pro
      inflammatory responses could also be enhanced by using siRNAs to silence the
      FOXO1 gene in WT VSMC, suggesting a negative regulatory role of FOXO1. FOXO1
      siRNAs and miR-135a mimics could both enhance the transcriptional activity of COX
      2 promoter. Using chromatin immunoprecipitation, we found that in db/db VSMC, the
      occupancy in promoter regions of inflammatory genes by FOXO1 was reduced.miR-135a
      increased the inflammatory responses of VSMC involved in complications of
      vascular diseases by downregulating the expression of FOXO1.

PMID- 29332917
TI  - Significance of Sarcopenia Evaluation in Acute Decompensated Heart Failure.
AB  - In patients with chronic heart failure (HF), the clinical importance of
      sarcopenia has been recognized in relation to disease severity, reduced exercise
      capacity, and adverse clinical outcome. Nevertheless, its impact on acute
      decompensated heart failure (ADHF) is still poorly understood. Dual-energy X-ray
      absorptiometry (DXA) is a technique for quantitatively analyzing muscle mass and
      the degree of sarcopenia. Fat-free mass index (FFMI) is a noninvasive and easily
      applicable marker of muscle mass.This was a prospective observational cohort
      study comprising 38 consecutive patients hospitalized for ADHF. Sarcopenia,
      derived from DXA, was defined as a skeletal muscle mass index (SMI) two standard
      deviations below the mean for healthy young subjects. FFMI (kg/m2) was calculated
      as 7.38 + 0.02908 * urinary creatinine (mg/day) divided by the square of height
      (m2).Sarcopenia was present in 52.6% of study patients. B-type natriuretic
      peptide (BNP) levels were significantly higher in ADHF patients with sarcopenia
      than in those without sarcopenia (1666 versus 429 pg/mL, P < 0.0001). Receiver
      operator curves were used to compare the predictive accuracy of SMI and FFMI for
      higher BNP levels. Areas under the curve for SMI and FFMI were 0.743 and 0.717,
      respectively. Multiple logistic regression analysis showed sarcopenia as a
      predictor of higher BNP level (OR = 18.4; 95% CI, 1.86-181.27; P =
      0.013).Sarcopenia is associated with increased disease severity in ADHF. SMI
      based on DXA is potentially superior to FFMI in terms of predicting the degree of
      severity, but FFMI is also associated with ADHF severity.

PMID- 29332918
TI  - Plasmatic MicroRNA Signatures in Elderly People with Stable and Unstable Angina.
AB  - We aimed to investigate the distinctive miRNA profiles in the plasma of elderly
      patients with unstable angina (UA) and stable angina (SA), and to find more
      effective markers of UA in elderly people. We compared miRNA expression levels in
      plasma samples from 10 elderly patients with UA and 10 elderly patients with SA
      by using microarray-based miRNA chip, and then performed validation with Real
      time PCR. Mir-1202, mir-1207-5p, and mir-1225-5p showed a statistically
      significant down-regulation (P < 0.05), while mir-3162-3p showed an up-regulation
      (P < 0.05) during validation. Among all single miRNAs, miR-3162-3p showed the
      highest discriminatory power in the diagnosis of elderly patients with UA (AUC:
      0.79, 95% CI: 0.675-0.905). The discriminatory power of a panel of three miRNAs
      (mir-3162-3p/mir-1225-5p/mir-1207-5p) was highest with an AUC of 0.91 (95% CI:
      0.84-0.98), followed by mir-3162-3p/mir-1225-5p (AUC: 0.833, 95% CI: 0.732-0.934)
      and mir-3162-3p/mir-1207-5p (AUC: 0.817, 95% CI: 0.712-0.922). In conclusion,
      multi-miRNA panel could provide higher diagnostic value for the diagnosis of
      elderly patients with UA.

PMID- 29332919
TI  - High-Intensity Interval Training for Severe Left Ventricular Dysfunction Treated
      with Left Ventricular Assist Device.
AB  - Aerobic training based on anaerobic threshold (AT) is well-known to improve
      cardiac function, exercise capacity, and long-term outcomes of patients with
      heart failure. Recent reports suggested that high-intensity interval training
      (HIIT) for patients with cardiovascular disease may improve cardiopulmonary
      exercise capacity. We present a 61-year-old male patient of severe left
      ventricular dysfunction with left ventricular assisted device (LVAD). Following
      HIIT for 8 weeks, exercise capacity and muscle strength have improved without
      worsening left ventricular function. Our case showed the possibility that HIIT
      was feasible and effective even in patients with LVAD.

PMID- 29332920
TI  - Aorto-Cutaneous Fistula after Surgical Treatment of Stanford Type A Aortic
      Dissection.
AB  - An aorto-cutaneous fistula is a rare complication that occurs after aortic
      surgery. Due to its rarity, postoperative complications are not normally
      highlighted in most standard teaching. We report here a case of aorto-cutaneous
      fistula after surgical treatment of a Stanford type A aortic dissection (AD) in a
      67-year-old Chinese male. The patient presented with severe right heart
      dysfunction and a mass was found in the upper-middle of his chest, which started
      bleeding in the next years. On admission, preoperative aortic computed tomography
      angiography (CTA) showed a huge hematoma located in the anterior superior
      mediastinum and a shunt between the embedding cavity of the aortic root and right
      atrium. An emergent procedure was performed. Intraoperatively, we found two leaks
      approximately 2 mm from the anastomosis of the greater curvature of the ascending
      aortic graft and stented graft after the hematoma was cleared and we confirmed
      the shunt had a large amount of blood flow after a right atrium incision. After
      the surgery, the patient was diagnosed with a cerebral hemorrhage, and his family
      decided to refuse therapy on the third postoperative day (p.o.d.).

PMID- 29332921
TI  - Early Diastolic Left Ventricular Relaxation in Normal Neonates is Influenced by
      Ventricular Stiffness and Longitudinal Systolic Function.
AB  - Tissue Doppler velocity during early diastole (e') is one of the most feasible
      and reproducible echocardiographic assessments to reflect active relaxation of
      the left ventricle. Although several reports have described the mechanisms of
      temporal diastolic dysfunction in the early neonatal period, factors influencing
      diastolic function have not been determined. The purpose of this study was to
      elucidate factors significantly influencing e' in the early neonatal period.A
      total of 179 consecutive normal neonates underwent echocardiographic studies
      performed at 0 days and 5-10 days after birth. The statistical relationships
      between e' and age, body weight, mean blood pressure, heart rate, shortening
      fraction of the left ventricle, peak systolic motion velocity (s'), early
      diastolic transmitral flow velocity over annulus velocity, Tei index, and
      diastolic wall strain (DWS) were analyzed.Between the 0 days and 5-10-days-after
      birth groups, significant differences were shown in mean blood pressure,
      shortening fraction of left ventricle, e', and Tei index. Age, body weight, mean
      blood pressure, s', and DWS showed significant correlations with e'. In
      multivariate regression analysis within these parameters, s' (beta = 0.6119, P <
      0.0001) and DWS (beta = 0.1216, P = 0.0321) showed positive correlations with
      e'.Longitudinal systolic motion velocity and ventricular wall stiffness of the
      left ventricle influence diastolic relaxation in normal neonates. Age, body
      weight, and circumferential systolic function are not significant factors.

PMID- 29332922
TI  - Role of Gene Polymorphisms/Haplotypes and Plasma Level of TGF-beta1 in
      Susceptibility to In-Stent Restenosis Following Coronary Implantation of Bare
      Metal Stent in Chinese Han Patients.
AB  - Transforming growth factor (TGF)-beta1 has been implicated in the pathogenesis of
      restenosis. However, the role of TGF-beta1 polymorphisms in development of in
      stent restenosis (ISR) after coronary bare metal stent (BMS) implantation in
      Chinese Han population has not been reported to date. The aim of this study was
      to explore the association between TGF-beta1 gene polymorphisms (-509C/T and
      869T/C) and its plasma level in Chinese Han patients with BMS-ISR.We investigated
      419 patients after successful coronary stent placement. All patients were
      reexamined by angiography. Genotyping for the two TGF-beta1 gene polymorphisms
      was performed using polymerase chain reaction-restriction fragment length
      polymorphism analysis. Plasma TGF-beta1 levels were measured by enzyme-linked
      immunosorbent assay.Ninety-two patients (21.96%) developed ISR during the follow
      up period. The multivariable analysis adjusted for potential confounders and it
      revealed that the C allele of TGF-beta1 869T/C polymorphism was linked to an
      increased risk of ISR in both additive (Per each C allele) and dominant (TC+CC
      versus TT) models with odds ratios (ORs) of 1.88 (95% confidence interval [CI]:
      1.21-2.84, P = 0.008) and 2.52 (95% CI: 1.40-4.80, P = 0.005), respectively. In
      accord with this, C-dominant CC/CT genotype was linked to higher plasma TGF-beta1
      level compared to TT genotype. One haplotype (TC) (-509T, +869C) was associated
      with an increased risk for ISR (OR = 1.48, 95% CI: 1.06-2.06, P = 0.010).The C
      allele of TGF-beta1 869T/C polymorphism, correlated with high plasma TGF-beta1
      level, represented an independent risk factor for BMS-ISR in Chinese Han patients
      with coronary artery disease.

PMID- 29332923
TI  - Heart Failure as an Aging-Related Phenotype.
AB  - The molecular pathophysiology of heart failure, which is one of the leading
      causes of mortality, is not yet fully understood. Heart failure can be regarded
      as a systemic syndrome of aging-related phenotypes. Wnt/beta-catenin signaling
      and the p53 pathway, both of which are key regulators of aging, have been
      demonstrated to play a critical role in the pathogenesis of heart failure.
      Circulating C1q was identified as a novel activator of Wnt/beta-catenin
      signaling, promoting systemic aging-related phenotypes including sarcopenia and
      heart failure. On the other hand, p53 induces the apoptosis of cardiomyocytes in
      the failing heart. In these molecular mechanisms, the cross-talk between
      cardiomyocytes and non-cardiomyocytes (e,g,. endothelial cells, fibroblasts,
      smooth muscle cells, macrophages) deserves mentioning. In this review, we
      summarize recent advances in the understanding of the molecular pathophysiology
      underlying heart failure, focusing on Wnt/beta-catenin signaling and the p53
      pathway.

PMID- 29332924
TI  - Multiple Recurrent Pseudoaneurysms after Endovascular Repair of Abdominal Aortic
      Aneurysm in a Patient with Behcet's Disease.
AB  - In Behcet's disease (BD) patients, endovascular repair is a reasonable
      alternative treatment for aortic aneurysms to avoid postoperative anastomotic
      pseudoaneurysms. However, there are some complications that may occur after
      endovascular repair. We herein report the case of a 40-year-old man with active
      BD developed recurrent aortic pseudoaneurysms at the proximal and distal margins
      of the stent graft and a femoral puncture site pseudoaneurysm 3 months after
      endovascular abdominal aortic aneurysm (AAA) repair. The aortic pseudoaneurysms
      were treated endovascularly, including the use of the chimney technique for the
      proximal pseudoaneurysm close to the renal arteries and the femoral
      pseudoaneurysm with surgical excision and reconstruction. Intensive
      immunosuppressive therapy was initiated immediately after the operation. The
      patient is in good condition without any complications at 8-month follow-up. This
      case suggests the utility of the chimney technique and postoperative immediate
      intensive immunosuppressive therapy in treating recurrent aortic pseudoaneurysms
      in emergency, active BD patients.

PMID- 29332925
TI  - Pulmonary Artery Pseudoaneurysm Secondary to Lung Inf lammation.
AB  - Pulmonary artery aneurysms (PAA) and pseudoaneurysms (PAP) are caused by
      infections, vasculitis, trauma, pulmonary hypertension, congenital heart disease,
      and connective tissue disease. Most cases of such aneurysm occur in the trunk or
      major branches of the pulmonary artery, while the peripheral type is less common.
      The treatment modalities are medical therapy, surgery, and percutaneous catheter
      embolization. The mortality rate associated with rupture is approximately 50%. We
      encountered a case of a 53-year-old man with a pulmonary artery pseudoaneurysm
      secondary to pneumonia and cavity formation during chemotherapy for acute myeloid
      leukemia (AML). In diagnosis, contrast-enhanced chest computed tomography (CT)
      scan and pulmonary angiography were very useful. He was treated with right middle
      and lower lobectomy. After 1-month follow-up, he could restart additional
      chemotherapy.

PMID- 29332927
TI  - The response of common marmoset immunity against cedar pollen extract.
AB  - The in vivo model of pollinosis has been established using rodents, but the model
      cannot completely mimic human pollinosis. We used Callithrix jacchus, the common
      marmoset (CM), to establish a pollinosis animal model using intranasal weekly
      administration of cedar pollen extract with cholera toxin adjuvant. Some of the
      treated CMs exhibited the symptoms of snitching, excess nasal mucus and/or
      sneezing, but the period was very short, and the symptoms disappeared after
      several weeks. The CD4+CD25+ cell ratio in the peripheral blood increased in CMs
      quickly after the nasal administration of cedar pollen extract, but the timing
      was not parallel with the symptoms. IL-10 mRNA was enhanced in the peripheral
      blood mononuclear cells (PBMCs), suggesting CM-induced tolerance for cedar pollen
      administration. Similarly, Foxp3 mRNA was also detected in the PBMC. Additive
      sensitization of these CMs with Ascaris egg administration did not enhance
      chronic inflammation of type 1 allergy to induce the symptoms. These results
      suggest that the environmental immune cells develop transient allergic symptoms
      and subsequent immune-tolerance in the intranasally sensitized CMs.

PMID- 29332926
TI  - Differentiating between Alzheimer Disease Patients and Controls with Phase
      difference-enhanced Imaging at 3T: A Feasibility Study.
AB  - PURPOSE: To test the feasibility of the phase difference enhanced (PADRE) imaging
      for differentiation between Alzheimer disease (AD) patients and control subjects
      on 3T MR imaging. MATERIALS AND METHODS: Fifteen patients with AD and 10 age
      matched control subjects underwent two-dimensional fast field echo imaging to
      obtain PADRE images on a 3T MR scanner. A double Gaussian distribution model was
      used to determine the threshold phase value for differentiation between the
      physiologic and non-physiologic iron in the cerebral cortices, and PADRE images
      were processed with the threshold. Using a 4-point grading system, two readers
      independently assessed the signal of the four cerebral cortices on PADRE images:
      the cuneus, precuneus, superior frontal gyrus, and superior temporal gyrus. The
      difference in the signals in each cortex between the AD patients and age-matched
      control subjects was determined by using Mann-Whitney U test. Inter-rater
      reliability was determined by Kappa analysis. We also evaluated the correlation
      between Mini-Mental State Examination (MMSE) score and the hypointense grade, and
      between disease duration and the hypointense grade using the Spearman rank
      correlation test. RESULTS: The threshold phase value for differentiation between
      the physiologic and non-physiologic iron was -4.6% pi (radian). The mean grades
      of the cuneus, precuneus, and superior temporal gyrus were significantly higher
      for the AD patients than for the control subjects (P = 0.002). Excellent inter
      rater reliability was seen in the precuneus (kappa = 0.93), superior temporal
      gyrus (kappa = 0.94), and superior frontal gyrus (kappa = 0.93); good inter-rater
      reliability was observed in the cuneus (kappa = 0.75). We found a statistical
      correlation between MMSE score and the hypointense grade in superior temporal
      gyrus (STG) (P = 0.008), and no correlation between disease duration and the
      hypointense grade in any gyrus. CONCLUSION: Our results suggest the feasibility
      of PADRE imaging at 3T for differentiation between AD patients and control
      subjects.

PMID- 29332928
TI  - Optical coherence tomography for precision brain imaging, neurosurgical guidance
      and minimally invasive theranostics.
AB  - This review focuses on optical coherence tomography (OCT)-based neurosurgical
      application for imaging and treatment of brain tumors. OCT has emerged as one of
      the most innovative and successful translational biomedical-diagnostic
      techniques. It is a useful imaging tool for noninvasive, in vivo, in situ and
      real-time imaging in soft biological tissues, such as brain tumor imaging. OCT
      can detect the structure of biological tissue in a micrometer scale, and
      functional OCT has some clinical researches and applications, such as nerve fiber
      tracts and neurovascular imaging. OCT is able to identify tumor margins, and it
      gives intraoperative precision identification and resection guidance. OCT-based
      theranostics is introduced into preclinical neurosurgical resection, such as the
      integration of OCT and laser ablation. We discuss the challenges and
      opportunities of OCT-based system in the field of combination of intraoperative
      structural and functional imaging, neurosurgical guidance and minimally invasive
      theranostics. We point out that OCT and laser ablation-based theranostics can
      give more precision and intelligence for intraoperative diagnosis and
      therapeutics in clinical applications. The theranostics can precisely locate, or
      specifically target cancerous tissues, and then as much as possiblly eliminate
      them.

PMID- 29332929
TI  - Size-Based Differentiation of Cancer and Normal Cells by a Particle Size Analyzer
      Assisted by a Cell-Recognition PC Software.
AB  - Detection of anomalous cells such as cancer cells from normal blood cells has the
      potential to contribute greatly to cancer diagnosis and therapy. Conventional
      methods for the detection of cancer cells are usually tedious and cumbersome.
      Herein, we report on the use of a particle size analyzer for the convenient size
      based differentiation of cancer cells from normal cells. Measurements made using
      a particle size analyzer revealed that size parameters for cancer cells are
      significantly greater (e.g., inner diameter and width) than the corresponding
      values for normal cells (white blood cells (WBC), lymphocytes and splenocytes),
      with no significant difference in shape parameters (e.g., circularity and
      convexity). The inner diameter of many cancer cell lines is greater than 10 um,
      in contrast to normal cells. For the detection of WBC having similar size to that
      of cancer cells, we developed a PC software "Cancer Cell Finder" that
      differentiates them from cancer cells based on brightness stationary points on a
      cell surface. Furthermore, the aforementioned method was validated for cancer
      cell/clusters detection in spiked mouse blood samples (a B16 melanoma mouse
      xenograft model) and circulating tumor cell cluster-like particles in the cat and
      dog (diagnosed with cancer) blood samples. These results provide insights into
      the possible applicability of the use of a particle size analyzer in conjunction
      with PC software for the convenient detection of cancer cells in experimental and
      clinical samples for theranostics.

PMID- 29332930
TI  - Bullosis Diabeticorum: A Rare Presentation with Immunoglobulin G (IgG) Deposition
      Related Vasculopathy. Case Report and Focused Review.
AB  - BACKGROUND Bullosis diabeticorum (BD) is a condition characterized by recurrent,
      spontaneous, and non-inflammatory blistering in patients with poorly controlled
      diabetes mellitus. While etiopathogenesis remains unclear, roles of neuropathy,
      vasculopathy and UV light are hypothesized. Most literature reports negative
      direct and indirect immunofluorescence findings in diabetics with bullous
      eruptions. Porphyria cutanea tarda, bullous pemphigoid, epidermolysis bullosa,
      and pseudoporphyria are other differential diagnoses of bullous lesions, and they
      must be excluded. CASE REPORT We present a 42-year-old African American male with
      long standing poorly controlled insulin dependent diabetes mellitus with blisters
      on his left hand and feet. The blisters were noticed three weeks prior to
      presentation and, thereafter, rapidly increased in size and spontaneously
      ruptured. Physical examination revealed a multitude of both roofed and unroofed
      bullous painless skin lesions. Hematoxylin and eosin (H&E) staining dramatized
      the dermal-epidermal blistering and re-epithelization process. Direct
      Immunofluorescence (DIF) was positive for 2 + IgG deposition in the already
      thickened basement membrane of the capillaries of the superficial vascular
      plexus. After debridement, his wounds greatly improved with over three months of
      aggressive wound care. CONCLUSIONS Primary immunologic abnormality likely plays
      no role in the onset of BD. To date, only one article has reported nonspecific
      capillary-associated immunoglobulin M and C3. This is the first case of BD with
      IgG deposition in the superficial capillary basement membrane. Positive findings
      on DIF suggest vasculopathy. Dermal microangiopathy, secondary to immunologic
      abnormality, is a possible underlying pathogenesis to bullae formation. Punch
      biopsy with DIF can be an additional diagnostic modality in the management of
      such cases.

PMID- 29332932
TI  - Thrombotic microangiopathy: Pregnancy outcomes in aHUS.

PMID- 29332933
TI  - Epigenetics: H3K27me3 in glomerular disease.

PMID- 29332931
TI  - Proteasome Inhibitor Carbobenzoxy-L-Leucyl-L-Leucyl-L-Leucinal (MG132) Enhances
      Therapeutic Effect of Paclitaxel on Breast Cancer by Inhibiting Nuclear Factor
      (NF)-kappaB Signaling.
AB  - BACKGROUND Carbobenzoxy-L-leucyl-L-leucyl-L-leucinal (MG132), a peptide aldehyde
      proteasome inhibitor, can inhibit tumor progression by inactivating nuclear
      factor (NF)-kappaB signaling. Paclitaxel (PTX) is part of a routine regimen for
      the treatment of breast cancer. However, activation of the NF-kappaB pathway
      after treatment with PTX confers insensitivity to this drug. This study
      investigated the potential effect of MG132 as a co-treatment with PTX against
      breast cancer, and clarifies the underlying molecular mechanisms. MATERIAL AND
      METHODS Breast cancer cells were treated with PTX, MG132, or PTX plus MG132, and
      the therapeutic effects were evaluated phenotypically. A mouse model of breast
      cancer was used to determine the combined effect of PTX plus MG132 in vivo.
      RESULTS Treatment with PTX plus MG132 suppressed aggressive phenotypes of breast
      cancer cells more effectively than PTX alone. Consistently, MG132 also enhanced
      the suppressive effect of PTX on tumor growth in C57BL/6 mice. Significantly,
      activation of the NF-kappaB pathway by PTX was attenuated by MG132. CONCLUSIONS
      Based on our findings, we suggest the application of MG132 in clinical practice
      in combination with PTX for the treatment of breast cancer.

PMID- 29332934
TI  - Sepsis: The podoplanin-CLEC2 axis in sepsis.

PMID- 29332938
TI  - Innate lymphoid cells: Lipid surveillance by skin ILCs.

PMID- 29332939
TI  - Metagenomics: Setting the bar for mycobiome analysis.

PMID- 29332936
TI  - Tissue-specific immunopathology during malaria infection.
AB  - Systemic inflammation mediated by Plasmodium parasites is central to malaria
      disease and its complications. Plasmodium parasites reside in erythrocytes and
      can theoretically reach all host tissues via the circulation. However, actual
      interactions between parasitized erythrocytes and host tissues, along with the
      consequent damage and pathological changes, are limited locally to specific
      tissue sites. Such tissue specificity of the parasite can alter the outcome of
      malaria disease, determining whether acute or chronic complications occur. Here,
      we give an overview of the recent progress that has been made in understanding
      tissue-specific immunopathology during Plasmodium infection. As knowledge on
      tissue-specific host-parasite interactions accumulates, better treatment
      modalities and targets may emerge for intervention in malaria disease.

PMID- 29332940
TI  - Cellular microbiology: Many pathogens, one host receptor.

PMID- 29332941
TI  - Bacterial pathogenesis: Clostridium difficile is sweet on trehalose.

PMID- 29332937
TI  - Improving immune-vascular crosstalk for cancer immunotherapy.
AB  - The vasculature of tumours is highly abnormal and dysfunctional. Consequently,
      immune effector cells have an impaired ability to penetrate solid tumours and
      often exhibit compromised functions. Normalization of the tumour vasculature can
      enhance tissue perfusion and improve immune effector cell infiltration, leading
      to immunotherapy potentiation. However, recent studies have demonstrated that the
      stimulation of immune cell functions can also help to normalize tumour vessels.
      In this Opinion article, we propose that the reciprocal regulation between tumour
      vascular normalization and immune reprogramming forms a reinforcing loop that
      reconditions the tumour immune microenvironment to induce durable antitumour
      immunity. A deeper understanding of these pathways could pave the way for
      identifying new biomarkers and developing more effective combination treatment
      strategies for patients with cancer.

PMID- 29332942
TI  - 1918 influenza virus: 100 years on, are we prepared against the next influenza
      pandemic?

PMID- 29332943
TI  - Bacterial physiology: It's a wrap for Burkholderia flagella.

PMID- 29332935
TI  - Novel treatment strategies for chronic kidney disease: insights from the animal
      kingdom.
AB  - Many of the >2 million animal species that inhabit Earth have developed survival
      mechanisms that aid in the prevention of obesity, kidney disease, starvation,
      dehydration and vascular ageing; however, some animals remain susceptible to
      these complications. Domestic and captive wild felids, for example, show
      susceptibility to chronic kidney disease (CKD), potentially linked to the high
      protein intake of these animals. By contrast, naked mole rats are a model of
      longevity and are protected from extreme environmental conditions through
      mechanisms that provide resistance to oxidative stress. Biomimetic studies
      suggest that the transcription factor nuclear factor erythroid 2-related factor 2
      (NRF2) offers protection in extreme environmental conditions and promotes
      longevity in the animal kingdom. Similarly, during months of fasting,
      immobilization and anuria, hibernating bears are protected from muscle wasting,
      azotaemia, thrombotic complications, organ damage and osteoporosis - features
      that are often associated with CKD. Improved understanding of the susceptibility
      and protective mechanisms of these animals and others could provide insights into
      novel strategies to prevent and treat several human diseases, such as CKD and
      ageing-associated complications. An integrated collaboration between
      nephrologists and experts from other fields, such as veterinarians, zoologists,
      biologists, anthropologists and ecologists, could introduce a novel approach for
      improving human health and help nephrologists to find novel treatment strategies
      for CKD.

PMID- 29332944
TI  - Fungal pathogenesis: Wheat stem rust effectors revealed.

PMID- 29332946
TI  - Optimal Groundwater Extraction under Uncertainty and a Spatial Stock Externality.
AB  - We introduce a model that incorporates two important elements to estimating
      welfare gains from groundwater management: stochasticity and a spatial stock
      externality. We estimate welfare gains resulting from optimal management under
      uncertainty as well as a gradual stock externality that produces the dynamics of
      a large aquifer being slowly exhausted. This groundwater model imposes an
      important aspect of a depletable natural resource without the extreme assumption
      of complete exhaustion that is necessary in a traditional single cell (bathtub)
      model of groundwater extraction. Using dynamic programming, we incorporate and
      compare stochasticity for both an independent and identically distributed as well
      as a Markov chain process for annual rainfall. We find that the spatial depletion
      of the aquifer is significant to welfare gains for a parameterization of a
      section of the Ogallala Aquifer in Kansas, ranging from 2.9% to 3.01%, which is
      larger than those found previously over the region. Surprisingly, the inclusion
      of stochasticity in rainfall increases welfare gains only slightly.

PMID- 29332947
TI  - A tunable coupler for superconducting microwave resonators using a nonlinear
      kinetic inductance transmission line.
AB  - We present a tunable coupler scheme that allows us to tune the coupling strength
      between a feedline and a superconducting resonator in situ over a wide range. In
      this scheme, we shunt the feedline with a 50-Omega lumped-element nonlinear
      transmission line made from a 20 nm NbTiN film. By injecting a DC current, the
      nonlinear kinetic inductance changes and the effective impedance shunting the
      resonator periodically varies from a short to an open, which tunes the coupling
      strength and coupling quality factor Qc . We have demonstrated Qc tuning over a
      factor of 40, between Qc ~ 5.5 * 104 and Qc ~ 2.3 * 106, for a 4.5 GHz resonator
      by applying a DC current less than 3.3 mA. Our tunable coupler scheme is easy to
      implement and may find broad applications in superconducting detector and quantum
      computing/information experiments.

PMID- 29332945
TI  - The human skin microbiome.
AB  - Functioning as the exterior interface of the human body with the environment,
      skin acts as a physical barrier to prevent the invasion of foreign pathogens
      while providing a home to the commensal microbiota. The harsh physical landscape
      of skin, particularly the desiccated, nutrient-poor, acidic environment, also
      contributes to the adversity that pathogens face when colonizing human skin.
      Despite this, the skin is colonized by a diverse microbiota. In this Review, we
      describe amplicon and shotgun metagenomic DNA sequencing studies that have been
      used to assess the taxonomic diversity of microorganisms that are associated with
      skin from the kingdom to the strain level. We discuss recent insights into skin
      microbial communities, including their composition in health and disease, the
      dynamics between species and interactions with the immune system, with a focus on
      Propionibacterium acnes, Staphylococcus epidermidis and Staphylococcus aureus.

PMID- 29332948
TI  - Comparison of areas in shadow from imaging and altimetry in the north polar
      region of Mercury and implications for polar ice deposits.
AB  - Earth-based radar observations and results from the MESSENGER mission have
      provided strong evidence that permanently shadowed regions near Mercury's poles
      host deposits of water ice. MESSENGER's complete orbital image and topographic
      datasets enable Mercury's surface to be observed and modeled under an extensive
      range of illumination conditions. The shadowed regions of Mercury's north polar
      region from 65 degrees N to 90 degrees N were mapped by analyzing Mercury Dual
      Imaging System (MDIS) images and by modeling illumination with Mercury Laser
      Altimeter (MLA) topographic data. The two independent methods produced strong
      agreement in identifying shadowed areas. All large radar-bright deposits, those
      hosted within impact craters >=6 km in diameter, collocate with regions of shadow
      identified by both methods. However, only ~46% of the persistently shadowed areas
      determined from images and ~43% of the permanently shadowed areas derived from
      altimetry host radar-bright materials. Some sizable regions of shadow that do not
      host radar-bright deposits experience thermal conditions similar to those that
      do. The shadowed craters that lack radar-bright materials show a relation with
      longitude that is not related to the thermal environment, suggesting that the
      Earth-based radar observations of these locations may have been limited by
      viewing geometry, but it is also possible that water ice in these locations is
      insulated by anomalously thick lag deposits or that these shadowed regions do not
      host water ice.

PMID- 29332950
TI  - Microwave evaluation of electromigration susceptibility in advanced
      interconnects.
AB  - Traditional metrology has been unable to adequately address the needs of the
      emerging integrated circuits (ICs) at the nano scale; thus, new metrology and
      techniques are needed. For example, the reliability challenges in fabrication
      need to be well understood and controlled to facilitate mass production of
      through-substrate-via (TSV) enabled three-dimensional integrated circuits (3D
      ICs). This requires new approaches to the metrology. In this paper, we use the
      microwave propagation characteristics to study the reliability issues that
      precede the physical damage caused by electromigration in the Cu-filled TSVs. The
      pre-failure microwave insertion losses and group delay are dependent on both the
      device temperature and the amount of current forced through the devices-under
      test. The microwave insertion losses increase with the increase in the test
      temperature, while the group delay increases with the increase in the forced
      direct current magnitude. The microwave insertion losses are attributed to the
      defect mobility at the Cu-TiN interface, and the group delay changes are due to
      resistive heating in the interconnects, which perturbs the dielectric properties
      of the cladding dielectrics of the copper fill in the TSVs.
      https://doi.org/10.1063/1.4992135.

PMID- 29332949
TI  - Convergent Synthesis of alpha-Branched Amines by Transition-Metal-Catalyzed C-H
      Bond Additions to Imines.
AB  - alpha-Branched amines are ubiquitous in drugs and natural products, and
      consequently, synthetic methods that provide convergent and efficient entry to
      these structures are of considerable value. Transition-metal-catalyzed C-H bond
      additions to imines have the potential to be highly practical and atom-economic
      approaches for the synthesis of a diverse and complex array of alpha-branched
      amine products. These strategies typically employ readily available starting
      inputs, display high functional group compatibility, and often avoid the
      production of stoichiometric waste byproducts. A number of C-H functionalization
      methods have also been developed that incorporate cascade cyclization pathways to
      give amine-substituted carbocycles, and in many cases, proceed with the formation
      of multiple stereogenic centers. Advances in the area of asymmetric C-H bond
      additions to imines have also been achieved through the use of chiral imine N
      substituents as well as by enantioselective catalysis.

PMID- 29332951
TI  - Soil seal development under simulated rainfall: Structural, physical and
      hydrological dynamics.
AB  - This study delivers new insights into rainfall-induced seal formation through a
      novel approach in the use of X-ray Computed Tomography (CT). Up to now seal and
      crust thickness have been directly quantified mainly through visual examination
      of sealed/crusted surfaces, and there has been no quantitative method to estimate
      this important property. X-ray CT images were quantitatively analysed to derive
      formal measures of seal and crust thickness. A factorial experiment was
      established in the laboratory using open-topped microcosms packed with soil. The
      factors investigated were soil type (three soils: silty clay loam - ZCL, sandy
      silt loam - SZL, sandy loam - SL) and rainfall duration (2-14 min). Surface seal
      formation was induced by applying artificial rainfall events, characterised by
      variable duration, but constant kinetic energy, intensity, and raindrop size
      distribution. Soil porosities derived from CT scans were used to quantify the
      thickness of the rainfall-induced surface seals and reveal temporal seal micro
      morphological variations with increasing rainfall duration. In addition, the
      water repellency and infiltration dynamics of the developing seals were
      investigated by measuring water drop penetration time (WDPT) and unsaturated
      hydraulic conductivity (Kun). The range of seal thicknesses detected varied from
      0.6 to 5.4 mm. Soil textural characteristics and OM content played a central role
      in the development of rainfall-induced seals, with coarser soil particles and
      lower OM content resulting in thicker seals. Two different trends in soil
      porosity vs. depth were identified: i) for SL soil porosity was lowest at the
      immediate soil surface, it then increased constantly with depth till the median
      porosity of undisturbed soil was equalled; ii) for ZCL and SL the highest
      reduction in porosity, as compared to the median porosity of undisturbed soil,
      was observed in a well-defined zone of maximum porosity reduction c. 0.24-0.48 mm
      below the soil surface. This contrasting behaviour was related to different
      dynamics and processes of seal formation which depended on the soil properties.
      The impact of rainfall-induced surface sealing on the hydrological behaviour of
      soil (as represented by WDTP and Kun) was rapid and substantial: an average 60%
      reduction in Kun occurred for all soils between 2 and 9 min rainfall, and water
      repellent surfaces were identified for SZL and ZCL. This highlights that the
      condition of the immediate surface of agricultural soils involving rainfall
      induced structural seals has a strong impact in the overall ability of soil to
      function as water reservoir.

PMID- 29332952
TI  - Disentangling orthogonal matrices.
AB  - Motivated by a certain molecular reconstruction methodology in cryo-electron
      microscopy, we consider the problem of solving a linear system with two unknown
      orthogonal matrices, which is a generalization of the well-known orthogonal
      Procrustes problem. We propose an algorithm based on a semi-definite programming
      (SDP) relaxation, and give a theoretical guarantee for its performance. Both
      theoretically and empirically, the proposed algorithm performs better than the
      naive approach of solving the linear system directly without the orthogonal
      constraints. We also consider the generalization to linear systems with more than
      two unknown orthogonal matrices.

PMID- 29332954
TI  - Determination of the Boltzmann constant with cylindrical acoustic gas
      thermometry: new and previous results combined.
AB  - We report a new determination of the Boltzmann constant kB using a cylindrical
      acoustic gas thermometer. We determined the length of the copper cavity from
      measurements of its microwave resonance frequencies. This contrasts with our
      previous work (Zhang et al 2011 Int. J. Thermophys.32 1297, Lin et al 2013
      Metrologia50 417, Feng et al 2015 Metrologia52 S343) that determined the length
      of a different cavity using two-color optical interferometry. In this new study,
      the half-widths of the acoustic resonances are closer to their theoretical values
      than in our previous work. Despite significant changes in resonator design and
      the way in which the cylinder length is determined, the value of kB is
      substantially unchanged. We combined this result with our four previous results
      to calculate a global weighted mean of our kB determinations. The calculation
      follows CODATA's method (Mohr and Taylor 2000 Rev. Mod. Phys. 72 351) for
      obtaining the weighted mean value of kB that accounts for the correlations among
      the measured quantities in this work and in our four previous determinations of
      kB. The weighted mean kB is 1.380 6484(28) * 10-23 J K-1 with the relative
      standard uncertainty of 2.0 * 10-6. The corresponding value of the universal gas
      constant is 8.314 459(17) J K-1 mol-1 with the relative standard uncertainty of
      2.0 * 10-6.

PMID- 29332953
TI  - Determination of the molar mass of argon from high-precision acoustic
      comparisons.
AB  - This article describes the accurate determination of the molar mass M of a sample
      of argon gas used for the determination of the Boltzmann constant. The method of
      one of the authors (Moldover et al 1988 J. Res. Natl. Bur. Stand.93 85-144) uses
      the ratio of the square speed of sound in the gas under analysis and in a
      reference sample of known molar mass. A sample of argon that was isotopically
      enriched in 40Ar was used as the reference, whose unreactive impurities had been
      independently measured. The results for three gas samples are in good agreement
      with determinations by gravimetric mass spectrometry; (<Macoustic/Mmass-spec> -
      1) = (-0.31 +/- 0.69) * 10-6, where the indicated uncertainty is one standard
      deviation that does not account for the uncertainties from the acoustic and mass
      spectroscopy references.

PMID- 29332955
TI  - Simultaneous segmentation and bias field estimation using local fitted images.
AB  - Level set methods often suffer from boundary leakage and inadequate segmentation
      when used to segment images with inhomogeneous intensities. To handle this issue,
      a novel region-based level set method was developed, in which two different local
      fitted images are used to construct a hybrid region intensity fitting energy
      functional. This novel method enables simultaneous segmentation of the regions of
      interest and estimation of the bias fields from inhomogeneous images. Our
      experiments on both synthetic images and a publicly available dataset demonstrate
      the feasibility and reliability of the proposed method.

PMID- 29332956
TI  - Fitness and Individuality in Complex Life Cycles.
AB  - Complex life cycles are common in the eukaryotic world, and they complicate the
      question of how to define individuality. Using a bottom-up, gene-centric
      approach, I consider the concept of fitness in the context of complex life
      cycles. I analyze the fitness effects of an allele (or a trait) on different
      biological units within a complex life history and how these effects drive
      evolutionary change within populations. Based on these effects, I attempt to
      construct a concept of fitness that accurately predicts evolutionary change in
      the context of complex life cycles.

PMID- 29332958
TI  - Kidney involvement in antiphospholipid syndrome - current diagnostic and
      management problems.

PMID- 29332957
TI  - In depth examination of impact of secondary reactive species on the apparent
      decoupling of poly(ethylene glycol) diacrylate hydrogel average mesh size and
      modulus.
AB  - Poly(ethylene glycol) diacrylate (PEGDA) hydrogels are widely used in
      biotechnology due to their in situ crosslinking capacity and tunable physical
      properties. However, as with all single component hydrogels, the modulus of PEGDA
      networks cannot be tailored independently of mesh size. This interdependence
      places significant limitations on their use for defined, 3D cell-microenvironment
      studies and for certain controlled release applications. The incorporation of
      secondary reactive species (SRS) into PEGDA hydrogels has previously been shown
      to allow the identification of up to 6 PEGDA hydrogel formulations for which
      distinct moduli can be obtained at consistent average mesh size (or vice versa).
      However, the modulus and mesh size ranges which can be probed by these
      formulations are quite restricted. This work presents an in-depth study of SRS
      incorporation into PEGDA hydrogels, with the goal of expanding the space for
      which "decoupled" examination of modulus and mesh size effects is achievable.
      Towards this end, over 100 PEGDA hydrogels containing either N-vinyl pyrrolidone
      or star PEG-tetraacrylate as SRS were characterized. To our knowledge, this is
      the first study to demonstrate that SRS incorporation allows for the
      identification of a number of modulus ranges that can be probed at consistent
      average mesh size (or vice versa).

PMID- 29332959
TI  - Changes in body composition and bone mineral density in postmenopausal women with
      psoriatic arthritis.
AB  - Objective: Prolonged inflammation status due to psoriatic arthritis (PsA) may
      contribute to the loss of muscle mass, extending from muscle weakness, and
      increased risk of falls and fractures. The risk of fractures and their
      complications increases with concomitant osteoporosis. Material and methods: The
      study included 95 women aged 50-75 years. The presence of sarcopenia was
      evaluated in a group of 51 women with PsA, and 44 controls (without inflammatory
      joint disease). Measurements of muscle mass and lean body mass were made using
      the method of bioimpedance assessing ALM (Appendicular Lean Mass) index and SMI
      (Skeletal Muscle Index). The diagnosis of sarcopenia was made in women with low
      muscle mass and concomitant reduction of the efficiency of the assessed
      functional test Timed Up and Go (TUG). Bone density measurement was done by
      densitometry in the femoral neck and lumbar spine. (Ethics statement OIL
      625/16/Bioet). Results: Sarcopenia, using ALM index and SMI, was diagnosed in
      13.7% and 43.1% of PsA women, and in healthy women in 9% and 20.4%, respectively.
      In the group of PsA, sarcopenia was associated with a significant increase in the
      occurrence of disorders of bone mineralisation (72.7% vs. 41.3% in patients
      without a decrease in muscle mass). There was no correlation between the loss of
      muscle mass, bone density, and activity of PsA. Conclusions: The prevalence of
      sarcopenia in postmenopausal women suffering from PsA is associated with the
      occurrence of osteoporosis.

PMID- 29332960
TI  - Nutrition and quality of life referring to physical abilities - a comparative
      analysis of a questionnaire study of patients with rheumatoid arthritis and
      osteoarthritis.
AB  - Objectives: A comparative analysis of opinions on diet and nutrition of patients
      suffering from rheumatoid arthritis (RA) and osteoarthritis (OA), and quality of
      life limited to physical abilities in both study groups. Material and methods: In
      the period from August to December 2012 an anonymous questionnaire survey was
      carried out among the patients of the Institute of Rheumatology. The respondents
      were asked to define their dietary preferences, dietary supplementation, and the
      level of physical limitations by completing the Health Assessment Questionnaire
      (HAQ). The study was carried out with the consent of the Bioethics Committee.
      Results: A total of 397 questionnaires were obtained. The majority of respondents
      were women (77%). 62% of RA patients (165 respondents) had been treated for over
      10 years as opposed to OA patients (80 respondents), where the largest group
      (33%) were patients during their first year. There is a significant difference in
      the disability level of patients in both compared groups. The average HAQ of RA
      patients was 1.09 and OA patients - 0.46. A change of dietary habits was declared
      by 32% of RA patients and by 17% of OA patients (p = 0.049) mostly without
      consulting a specialist - it concerned mainly limiting the consumption of sweets
      (30% vs. 21%), a meatless diet: 19% vs. 14%, and a non-dairy diet: 9% vs. 14%.
      Conclusions: Regardless of their diagnosis, the respondents believe that the way
      of eating affects their health. There are visible differences between diet and
      dietary supplementation, depending on the diagnosis of the disease. Differences
      were also observed in physical limitations of both patient groups - a higher
      level of disability was noted among RA patients. It is necessary to continue the
      topic at the level of clinical trials and medical experiments within the scope of
      the impact of diet as a supportive element in the treatment of rheumatic
      diseases.

PMID- 29332961
TI  - The usefulness of histopathological examinations of non-renal biopsies in the
      diagnosis of granulomatosis with polyangiitis.
AB  - Introduction: Granulomatosis with polyangiitis (GPA) is a rare, ANCA-associated,
      systemic disease characterized by necrotizing small and medium vessel vasculitis
      of unknown etiology associated with granulomatous inflammation affecting the
      renal, pulmonary, upper airways, ocular systems and other tissues. Histological
      proof of the granulomatosis with polyangiitis (GPA) can be obtained by biopsy of
      clinically involved sites. The main purpose of this study was to examine
      histopathological changes in non-renal biopsies from patients with established
      diagnosis of GPA and evaluated the histological confirmation at diagnosis of this
      disease. Material and methods: A retrospective analysis was performed in patients
      with GPA diagnosed and treated in clinics of the University Clinical Center (UCK)
      in Gdansk in 1988-2009. Results: In the analyzed group of GPA patients the
      histopathological examination of biopsies taken from involved tissues (except
      kidney) was performed in 60% of patients. Thirty-six out of 93 biopsies (39%)
      were diagnosed as typical of GPA, 10 (10.7%) were suggestive and 51 (54.8%) were
      non-specific. Considering all biopsies, the diagnosis was confirmed in 24
      patients (57% of patients in whom biopsies were taken). Epitheloid cell
      granulomas were present in 33 biopsies (43%), characteristic necrosis in 27
      biopsies (35%), small vessel vasculitis in 18 biopsies (23%), while
      multinucleated giant cells were identified only in 9 biopsies (12%). Conclusions:
      Histopathological examination of the affected tissues remains the gold standard
      of the diagnosis of GPA. Its usefulness increases, particularly in ANCA-negative
      patients, in the initial phase of the disease, or in patients with atypical
      clinical presentation. In many cases, it is necessary to repeat biopsy to
      establish the diagnosis. The role of the histopathological examination seems to
      be particularly important when ANCA is negative or clinical symptoms are atypical
      of GPA.

PMID- 29332962
TI  - The importance of physiotherapy in the sexuality of patients with rheumatic
      diseases.
AB  - The sexuality of patients with rheumatic diseases is a significant
      interdisciplinary problem, requiring intensified action not only of
      rheumatologists, sexologists, and psychologists but also physiotherapists. The
      sexuality problems and motor disability in chronic diseases such as rheumatoid
      arthritis or ankylosing spondylitis, as well as other rheumatic diseases, are
      generally still taboo subjects, rarely discussed by physicians and
      physiotherapists. Lack of mobility, hormonal imbalance, fatigue, and accompanying
      decreased quality of life have an impact on sexual dysfunction. Meanwhile sex, as
      an integral part of human personality, is an essential element of human life.

PMID- 29332963
TI  - Role of human microbiome and selected bacterial infections in the pathogenesis of
      rheumatoid arthritis.
AB  - Microorganisms inhabiting human body form a complex ecosystem. The mutual
      influence of the microbiome and the immune system of the host constitute the
      basis for numerous diseases, e.g. pseudomembranous colitis, inflammatory bowel
      disease, type 1 diabetes, atopic diseases, obesity, reactive arthritis. New
      molecular diagnostic methods and multi-center studies may help in understanding
      of the role of microbiota in health and disease. Rheumatoid arthritis has a multi
      faceted etiology, and its causes are not entirely understood. There are
      indications for the influence of microbiomes of oral cavity, intestines, lungs
      and urinary tract on the development of rheumatoid arthritis. Interactions
      between microorganisms and human immune system play role in the pathogenesis of
      the disease.

PMID- 29332964
TI  - Relapse of polymyalgia rheumatica after a fall.
AB  - Approximately half of PMR patients have a relapse with a necessity to increase GC
      dosages. The role of external factors in inducing PMR relapse have been poorly
      investigated. We present a case-series of five PMR patients in remission with low
      doses of glucocorticosteroids (GC), who presented with relapse immediately after
      a fall. The assessment of PMR relapse was made using PMR-AS by Leeb and Bird, and
      a score > 9.35 was consistent with diagnosis of relapse. Gender, age, and
      cumulative dose of GC at the time of the fall were compared between the group of
      these five patients and a group of 41 PMR patients who had no PMR relapse after a
      fall: using the Fischer's exact test a significant difference was pointed out
      when the p-value was < 0.05. In our five PMR patients, the sharp worsening of
      clinical manifestations was always accompanied by a significant rise of the
      inflammatory indices and the increase of GC dosage (almost always 10 mg/day of
      prednisone) prompted a fast return (seven days as average) to the previous
      clinical and laboratory features. All other potentially responsible factors were
      excluded. Several months (6-10 months on average) after the fall, none of these
      five patients had a new relapse. No significant differences were found when we
      compared age, sex, and the cumulative dose of GC at the time of the fall between
      the group of patients with PMR relapse and the group of patients without. The
      possibility of PMR relapse being realised immediately after a fall should be kept
      in mind in daily practice, especially when typical manifestations reappear
      immediately after a fall and other diagnostic hypotheses have been carefully
      excluded. The lack of important data (genetic factors, hormonal dosages, serum
      levels of IL-6 and/or serum soluble IL-6 receptor) in our case-series represented
      important limits for clarifying the nature of our observations and should be
      included in any subsequent study design on this argument. If our monocentric data
      are confirmed by multicentric data, the assessment of the risk of falls through
      specific scales should be an integral part of the visit of all PMR patients.

PMID- 29332965
TI  - Two clinical cases of granulomatosis with polyangiitis with isolated otitis media
      and mastoiditis.
AB  - Granulomatosis with polyangiitis (GPA) is characterised by granulomatous
      necrotising inflammatory lesions of the upper and lower respiratory tract, often
      associated with pauci-immune glomerulonephritis. The diagnosis of granulomatosis
      with polyangiitis is made according to the classification criteria of the ACR
      criteria for granulomatosis with polyangiitis. We present two cases of
      granulomatosis with polyangiitis limited/localised form. The common feature
      between two clinical cases were not sufficient criteria for a definite diagnosis
      at the beginning. In both cases the clinical presence was otitis media with acute
      mastoiditis, peripheral facial nerve palsy, and severe headache. Early diagnosis
      and treatment of patients with granulomatosis with polyangiitis define favourable
      prognosis. On the other hand, the treatment of granulomatosis with polyangiitis
      (corticosteroids and immunosuppressive therapy) has various side effects, and the
      "ex juvantibus" therapy is hazardous.

PMID- 29332966
TI  - When nuisance is nice: ignored erythema nodosa heralding the Lofgren's syndrome
      in a Nigerian woman.
AB  - Lofgren's syndrome (LS) is a variant of sarcoidosis characterised by the triad of
      erythema nodosum (EN), radiographic bilateral hilar adenopathy, and
      arthralgia/arthritis. Like all cases of sarcoidosis, it is of unknown aetiology
      and may constitute a diagnostic difficulty in the ambiguous phenotype. Lofgren's
      syndrome is associated with a good prognosis and commonly undergoes spontaneous
      remission within four months. However, the co-existence of multiple good and
      adverse prognostic factors in a patient may call for guarded expectation.
      Sarcoidosis is generally more prevalent among people of African descent, but the
      vast majority of the literature on sarcoidosis are from the western hemisphere.
      Lofgren's syndrome has been rarely documented in West Africans despite the
      availability of some reports of sarcoidosis in the region. We present a case of a
      Nigerian woman with LS that started out as isolated EN, which was ignored for
      months until the onset of florid pulmonary and systemic symptoms.

PMID- 29332967
TI  - Professor Henryka Maldyk (1924-2017).

PMID- 29332968
TI  - 50 years of the Polish Physician-Writers Union.

PMID- 29332969
TI  - C12H12 interconversions: two non-pyrolytic syntheses of
      tricyclo[5.3.2.04,8]dodeca-2,5,9,11-tetraene.
AB  - Herein, we describe two independent and non-pyrolytic syntheses of an important
      C12H12 hydrocarbon which had been prepared previously by gas phase thermolysis of
      compound 6. The first method is based on an unusual dipolar cycloaddition of
      dichloroketene onto bullvalene. After reductive dechlorination, a Shapiro-Heath
      reaction of the tosylhydrazone gave the title compound. Alternatively, compound
      13 is also obtained from its isomer 6 by a Ag+ catalyzed reaction.

PMID- 29332970
TI  - MIGRATION AND CONSERVATION: FRAMEWORKS, GAPS, AND SYNERGIES IN SCIENCE, LAW, AND
      MANAGEMENT.
AB  - Migratory animals provide unique spectacles of cultural, ecological, and economic
      importance. However, the process of migration is a source of risk for migratory
      species as human actions increasingly destroy and fragment habitat, create
      obstacles to migration, and increase mortality along the migration corridor. As a
      result, many migratory species are declining in numbers. In the United States,
      the Endangered Species Act provides some protection against extinction for such
      species, but no protection until numbers are severely reduced, and no guarantee
      of recovery to population levels associated with cultural, ecological, or
      economic significance. Although groups of species receive some protection from
      statutes such as the Migratory Bird Treaty Act and Marine Mammal Protection Act,
      there is no coordinated system for conservation of migratory species. In
      addition, information needed to protect migratory species is often lacking,
      limiting options for land and wildlife managers who seek to support these
      species. In this Article, we outline the existing scientific, legal, and
      management information and approaches to migratory species. Our objective is to
      assess present capacity to protect the species and the phenomenon of migration,
      and we argue that al three disciplines are necessary for effective conservation.
      We find significant capacity to support conservation in all three disciplines,
      but no organization around conservation of migration within any discipline or
      among the three disciplines. Areas of synergy exist among the disciplines but not
      as a result of any attempt for coordination. As a result, significant gaps in
      information and capacity exist that must be addressed if effective conservation
      of migratory species is to be undertaken. We suggest that all three disciplines
      cooperate to identify the most pressing research needs, so that these can become
      targets for relevant funding sources. We identify areas of current risk to
      migratory species that represent gaps in current legal protections: protective
      legislation that provides no guidelines for desirable population sizes or best
      management practices for migratory species, taxonomic groups, particularly those
      including long-distance migrants, for which no agency has oversight, and gaps in
      policies to address impacts of fragmentation and obstacles such as power lines
      and wind turbines that curtail migration or cause mortality. Finally, we suggest
      that state-level programs provide either a foundation to augment with, or a model
      on which to build, conservation efforts targeting migratory species. Problems
      will arise due to lack of funds, difficulties in securing a landscape that will
      support abundant migrations, lack of adequate standards and best management
      practices, and an insufficient culture of collaboration among the three main
      relevant disciplines. However, we view these problems as entirely soluble and see
      evidence of support in society at large for conservation of migratory species.

PMID- 29332971
TI  - TENSOR DECOMPOSITIONS AND SPARSE LOG-LINEAR MODELS.
AB  - Contingency table analysis routinely relies on log-linear models, with latent
      structure analysis providing a common alternative. Latent structure models lead
      to a reduced rank tensor factorization of the probability mass function for
      multivariate categorical data, while log-linear models achieve dimensionality
      reduction through sparsity. Little is known about the relationship between these
      notions of dimensionality reduction in the two paradigms. We derive several
      results relating the support of a log-linear model to nonnegative ranks of the
      associated probability tensor. Motivated by these findings, we propose a new
      collapsed Tucker class of tensor decompositions, which bridge existing PARAFAC
      and Tucker decompositions, providing a more flexible framework for parsimoniously
      characterizing multivariate categorical data. Taking a Bayesian approach to
      inference, we illustrate empirical advantages of the new decompositions.

PMID- 29332972
TI  - Clinical Utility and Measurement of Procalcitonin.
AB  - Procalcitonin (PCT), regarded as a biomarker specific for bacterial infections,
      is used in a variety of clinical settings including primary care, emergency
      department and intensive care. PCT measurement aids in the diagnosis of sepsis
      and to guide and monitor antibiotic therapy. This article gives a brief overview
      of PCT and its use in guiding antibiotic therapy in various clinical settings, as
      well as its limitations. PCT performance in comparison with other biomarkers of
      infection in particular CRP is also reviewed. Owing to its greater availability,
      CRP has been widely used as a biomarker of infection and sepsis. PCT is often
      reported to be more superior to CRP, being more specific for sepsis and bacterial
      infection. PCT starts to rise earlier and returns to normal concentration more
      rapidly than CRP, allowing for an earlier diagnosis and better monitoring of
      disease progression.

PMID- 29332974
TI  - The Management of Post Analytical Correction Factors.
AB  - Clinical laboratories may systematically apply factors to assay results after
      analysis, but before reporting, in order to facilitate comparison of data from
      different methods. This may be done to align with other patient results,
      reference intervals or clinical decision points. These factors, which we term
      Post Analytical Correction Factors (PACF), may be applied to all types of results
      derived from the method, i.e. quality control (QC) and external quality assurance
      (EQA), as well as the patient results. As the principal use of PACF is comparing
      patient results, it is important that the laboratory use commutable materials
      (i.e. patient samples) and a formal process to establish, apply and manage PACF.
      We report on preliminary guidelines for PACF from a recent workshop.

PMID- 29332975
TI  - Enhancing the Clinical Value of Medical Laboratory Testing.
AB  - The value of medical laboratory testing is often directed to the cost of testing
      however the clinical benefits of these tests are at least as important.
      Laboratory testing has an acknowledged widespread role in clinical decision
      making, and therefore a role in determining clinical outcome. Consequently, the
      value of laboratory testing should be considered in its role in affecting
      beneficial actions and outcomes. This includes both the requesting phase of
      choosing tests which will influence clinical decision making as well as the
      reporting phase in a way that guides clinical decisions and actions. Clinical
      decision support systems and software can enhance the value of medical laboratory
      testing if they are directed toward facilitating those clinical decisions where
      there is either evidence, or agreed consensus, addressing patient outcomes.

PMID- 29332976
TI  - Australasian Guideline (2nd Edition): an Annex to the CLSI and UK Guidelines for
      the Performance of the Sweat Test for the Diagnosis of Cystic Fibrosis.

PMID- 29332973
TI  - Metabologenomics of Phaeochromocytoma and Paraganglioma: An Integrated Approach
      for Personalised Biochemical and Genetic Testing.
AB  - The tremendous advances over the past two decades in both clinical genetics and
      biochemical testing of chromaffin cell tumours have led to new considerations
      about how these aspects of laboratory medicine can be integrated to improve
      diagnosis and management of affected patients. With germline mutations in 15
      genes now identified to be responsible for over a third of all cases of
      phaeochromocytomas and paragangliomas, these tumours are recognised to have one
      of the richest hereditary backgrounds among all neoplasms. Depending on the
      mutation, tumours show distinct differences in metabolic pathways that relate to
      or even directly impact clinical presentation. At the same time, there has been
      improved understanding about how catecholamines are synthesised, stored, secreted
      and metabolised by chromaffin cell tumours. Although the tumours may not always
      secrete catecholamines it has become clear that almost all continuously produce
      and metabolise catecholamines. This has not only fuelled changes in laboratory
      medicine, but has also assisted in recognition of genotype-biochemical phenotype
      relationships important for diagnostics and clinical care. In particular,
      differences in catecholamine and energy pathway metabolomes can guide genetic
      testing, assist with test interpretation and provide predictions about the
      nature, behaviour and imaging characteristics of the tumours. Conversely, results
      of genetic testing are important for guiding how routine biochemical testing
      should be employed and interpreted in surveillance programmes for at-risk
      patients. In these ways there are emerging needs for modern laboratory medicine
      to seamlessly integrate biochemical and genetic testing into the diagnosis and
      management of patients with chromaffin cell tumours.

PMID- 29332978
TI  - Playful pigs: Evidence of consistency and change in play depending on litter and
      developmental stage.
AB  - Play behaviour in pre-weaned piglets has previously been shown to vary
      consistently between litters. This study aimed to determine if these pre-weaning
      litter differences in play behaviour were also consistent in the post-weaning
      period. Seven litters of commercially bred piglets were raised in a free
      farrowing system (PigSAFE) and weaned at 28 days post-farrowing (+/-2 days). Post
      weaning piglets were maintained in litter groups in the PigSAFE pen. Analyses
      have been adjusted for sex both within and between litter as the only
      statistically significant covariate to play behaviour. Litter differences were
      observed in locomotor play in both the pre- and post-weaning stage (Pre: F(6,76)
      = 5.51 P < 0.001; Post: F(6,69) = 4.71, P < 0.001) and run (Pre: F(6,76) = 4.96,
      P < 0.001; Post: F(6,69) = 4.58, P < 0.001; the major element of locomotor play).
      Twenty eight% of the variance for a single observed animal in pre-weaning
      locomotor play and 26% of variance post-weaning could be attributed to the
      litter. There was no statistical evidence of differences in social play between
      litters at either stage with only 8% of pre-weaning variance, and 1% of post
      weaning variance being attributable to the litter level. However non-harmful
      fighting (the major element of social play), showed strong evidence of litter
      differences in both periods (Pre: F(6,76) = 2.38, P = 0.037; Post: F(6,69) =
      2.60, P = 0.025), and was the only aspect of the play behaviour to correlate
      between the pre- and post-weaning periods (r = 0.765, df = 5, P = 0.045). On
      average play increased post-weaning. Litters showed a 'litter weaning effect' by
      differing in their locomotor play behavioural response to weaning, measured as
      the change in locomotor play behaviour from pre- to post-weaning (F(6,70) = 5.95,
      P < 0.001). These results generally confirm previous work showing litter
      differences in aspects of play behaviour in both the pre and post-weaning period.
      However, there was no consistency in litter differences between pre- and post
      weaning periods in the categories of play behaviour with the exception of non
      harmful fighting. We demonstrated a 'litter weaning effect' where litters respond
      as a 'unit' to weaning in terms of their locomotory play behaviour. In general
      these results add further support to the use of play as a sensitive welfare
      indicator in neonatal pigs.

PMID- 29332979
TI  - Standardized maximim D-optimal designs for enzyme kinetic inhibition models.
AB  - Locally optimal designs for nonlinear models require a single set of nominal
      values for the unknown parameters. An alternative is the maximin approach that
      allows the user to specify a range of values for each parameter of interest.
      However, the maximin approach is difficult because we first have to determine the
      locally optimal design for each set of nominal values before maximin types of
      optimal designs can be found via a nested optimization process. We show that
      particle swarm optimization (PSO) techniques can solve such complex optimization
      problems effectively. We demonstrate numerical results from PSO can help find,
      for the first time, formulae for standardized maximin D-optimal designs for
      nonlinear model with 3 or 4 parameters on the compact and nonnegative design
      space. Additionally, we show locally and standardized maximin D-optimal designs
      for inhibition models are not necessarily supported at a minimum number of
      points. To facilitate use of such designs, we create a web-based tool for
      practitioners to find tailor-made locally and standardized maximin optimal
      designs.

PMID- 29332977
TI  - The Role of Wnt Signalling in Angiogenesis.
AB  - Angiogenesis is a normal biological process wherein new blood vessels form from
      the growth of pre-existing blood vessels. Preventing angiogenesis in solid
      tumours by targeting pro-angiogenic factors including vascular endothelial growth
      factor (VEGF), angiopoietin-1 (Ang-1), basic fibroblast growth factor (bFGF),
      hepatocyte growth factor, and platelet-derived growth factor (PDGF) is currently
      under investigation for cancer treatment. Concurrently targeting the cell
      signalling pathways involved in the transcriptional and post-translational
      regulation of these factors may provide positive therapeutic results. One such
      pathway is the Wnt signalling pathway. Wnt was first discovered in mice infected
      with mouse mammary tumour virus, and has been crucial in improving our
      understanding of oncogenesis and development. In this review, we summarise
      molecular and cellular aspects of the importance of Wnt signalling to
      angiogenesis, including beta-catenin-dependent mechanisms of angiogenic
      promotion, as well as the study of Wnt antagonists, such as the secreted frizzled
      related protein family (SFRPs) which have been shown to inhibit angiogenesis. The
      growing understanding of the underlying complexity of the biochemical pathways
      mediating angiogenesis is critical to the identification of new molecular targets
      for therapeutic applications.

PMID- 29332980
TI  - Domain-Specific Daily Hassles, Anxiety, and Delinquent Behaviors among Low
      Income, Urban Youth.
AB  - We studied contributions of domain-specific daily hassles to anxiety and
      delinquency prior to and during the transition into middle (N = 186) or high
      school (N = 167) in a sample of low-income, urban adolescents (93% African
      American; 54% female) using a two-wave longitudinal design. Path models
      controlling for baseline maladjustment and sex examined how hassles from parents,
      peers, academics, and the neighborhood were associated with maladjustment once
      youth had made the transition into a new school. Hassles with friends both prior
      to and during the school transition mattered for older youth's maladjustment
      only, whereas hassles with parents mattered for both older and younger youth.
      Academic hassles only appeared to be problematic for younger youth. Neighborhood
      hassles were associated in opposite ways with younger and older youth's
      maladjustment. These findings suggest that both hassle type and the timing of the
      school transition matter for youth maladjustment.

PMID- 29332981
TI  - The Unique and Interactive Effects of Parent and School Bonds on Adolescent
      Delinquency.
AB  - Parent and school bonds are protective against delinquency. This study used
      longitudinal data and multilevel Poisson regression models (MLM) to examine
      unique and interactive associations of parent and school bonds on youth
      delinquency in a sample of rural adolescents (n = 945; 84% White). We
      investigated whether youth sex or transitioning to a new middle school moderated
      the linkages between parent and school bonds and later delinquency. Results
      indicated reduced delinquency was associated with positive parent and school
      relationships. Parent and school bonds interacted such that linkages between
      parent bonding and youth delinquency were stronger when youth also had high
      school bonding - suggesting an additive effect. However, interactive effects were
      only found when youth remained in the same school and became nonsignificant if
      they transitioned to a new school. Findings support prior evidence that parent
      and school bonds - and their interaction - play a unique role in reducing
      delinquency.

PMID- 29332982
TI  - Attachment, Social Information Processing, and Friendship Quality of Early
      Adolescent Girls and Boys.
AB  - Sixth-graders (N = 223; 109 girls) completed questionnaires assessing their
      attachment security with their mothers and fathers, their social information
      processing (SIP) when faced with ambiguously caused hypothetical negative events
      involving a close friend, and the quality of the relationship with that friend.
      Aspects of more maladaptive SIP were significantly related to lower levels of
      security. The overall pattern of results did not provide strong evidence for
      mediation, although boys' anger did tend to mediate the relation between
      attachment to mother and friendship quality. Results are consistent with
      attachment theory and suggest that the mechanisms connecting attachment and
      friendship are specific with regard to the relationships boys and girls have with
      their fathers and mothers.

PMID- 29332983
TI  - Distinguishing Children Who Form New Best-Friendships from Those Who Do Not.
AB  - Three groups were identified using best-friendship nominations at two time points
      surrounding the transition to middle school (Time 1: Spring of 5th grade; Time 2:
      Fall of 6th grade): (i) children who had no best-friendship at Time 1, but had a
      best-friendship at Time 2 (best-friendship gain; N=109); (ii) children who had no
      best-friendship at either Time 1 or 2 (chronically best-friendless; N=105); and
      (iii) children with a best-friendship at both Times 1 and 2, but with different
      peers at each time (best-friendship change; N=120). Peer nominations of social
      behaviors and victimization were collected at Times 1 and 2. Findings suggest
      that attraction to similar others, in addition to increased displays of prosocial
      behaviors, facilitate the formation of new best-friendships for both initially
      best-friendless and best-friended children.

PMID- 29332984
TI  - White Matter Fiber-based Analysis of T1w/T2w Ratio Map.
AB  - Purpose: To develop, test, evaluate and apply a novel tool for the white matter
      fiber-based analysis of T1w/T2w ratio maps quantifying myelin content.
      Background: The cerebral white matter in the human brain develops from a mostly
      non-myelinated state to a nearly fully mature white matter myelination within the
      first few years of life. High resolution T1w/T2w ratio maps are believed to be
      effective in quantitatively estimating myelin content on a voxel-wise basis. We
      propose the use of a fiber-tract-based analysis of such T1w/T2w ratio data, as it
      allows us to separate fiber bundles that a common regional analysis imprecisely
      groups together, and to associate effects to specific tracts rather than large,
      broad regions. Methods: We developed an intuitive, open source tool to facilitate
      such fiber-based studies of T1w/T2w ratio maps. Via its Graphical User Interface
      (GUI) the tool is accessible to non-technical users. The framework uses
      calibrated T1w/T2w ratio maps and a prior fiber atlas as an input to generate
      profiles of T1w/T2w values. The resulting fiber profiles are used in a
      statistical analysis that performs along-tract functional statistical analysis.
      We applied this approach to a preliminary study of early brain development in
      neonates. Results: We developed an open-source tool for the fiber based analysis
      of T1w/T2w ratio maps and tested it in a study of brain development.

PMID- 29332985
TI  - CIVILITY: Cloud based Interactive Visualization of Tractography Brain Connectome.
AB  - Cloud based Interactive Visualization of Tractography Brain Connectome (CIVILITY)
      is an interactive visualization tool of brain connectome in the cloud. This
      application submits tasks to remote computing grids were the CIVILITY
      tractography pipeline is deployed. The application will list the running tasks
      for the user and once a task is completed the brain connectome is visualized
      using Hierarchical Edge Bundling. The analysis pipeline uses FSL tools (bedpostx
      and probtrackx2) to generate a triangular matrix indicating the connectivity
      strength between different regions in the brain. This work is motivated by
      medical applications in which expensive computational tasks such as brain
      connectivity is needed and to provide a state of the art visualization tool of
      Brain Connectome. This work does not contribute any novelty with respect to the
      visualization methodology, is rather a new resource for the neuroimaging
      community. This work is submitted to the SPIE Biomedical Applications in
      Molecular, Structural, and Functional Imaging conference. The source code of this
      application is available in NITRC.

PMID- 29332986
TI  - FADTTSter: Accelerating Hypothesis Testing With Functional Analysis of Diffusion
      Tensor Tract Statistics.
AB  - Functional Analysis of Diffusion Tensor Tract Statistics (FADTTS) is a toolbox
      for analysis of white matter (WM) fiber tracts. It allows associating diffusion
      properties along major WM bundles with a set of covariates of interest, such as
      age, diagnostic status and gender, and the structure of the variability of these
      WM tract properties. However, to use this toolbox, a user must have an
      intermediate knowledge in scripting languages (MATLAB). FADTTSter was created to
      overcome this issue and make the statistical analysis accessible to any non
      technical researcher. FADTTSter is actively being used by researchers at the
      University of North Carolina. FADTTSter guides non-technical users through a
      series of steps including quality control of subjects and fibers in order to
      setup the necessary parameters to run FADTTS. Additionally, FADTTSter implements
      interactive charts for FADTTS' outputs. This interactive chart enhances the
      researcher experience and facilitates the analysis of the results. FADTTSter's
      motivation is to improve usability and provide a new analysis tool to the
      community that complements FADTTS. Ultimately, by enabling FADTTS to a broader
      audience, FADTTSter seeks to accelerate hypothesis testing in neuroimaging
      studies involving heterogeneous clinical data and diffusion tensor imaging. This
      work is submitted to the Biomedical Applications in Molecular, Structural, and
      Functional Imaging conference. The source code of this application is available
      in NITRC.

PMID- 29332987
TI  - Elevated Serum miR-7, miR-9, miR-122, and miR-141 Are Noninvasive Biomarkers of
      Acute Pancreatitis.
AB  - Background: It has been reported that several microRNAs (miRNAs), such as miR
      141, miR-9, and miR-122, are involved in the regulation of pancreatitis-related
      proteins or that their levels change in acute pancreatitis (AP) animal models.
      However, the serum levels, as well as the clinical diagnostic and prognostic
      values, of these miRNAs in AP patients remain unclear. Furthermore, as a pancreas
      (islet) enriched miRNA, miR-7 was reported to be downregulated in AP patients,
      which requires further verification. Methods: The levels of miR-7, miR-9, miR
      122, and miR-141 were examined and compared using qRT-PCR among 80 severe AP
      patients, 80 mild AP patients, and 74 healthy controls. Results: The serum levels
      of these four miRNAs were increased markedly in the AP patients compared with the
      controls, and these levels decreased significantly after effective therapy.
      Particularly, the level of miR-7 was higher in severe AP patients than in mild AP
      patients. ROC curve analysis demonstrated that four miRNAs could be used as
      potential biomarkers for AP. Moreover, these miRNAs showed strong positive
      correlations with CRP, which may be associated with inflammation. Conclusions:
      The serum miR-7, miR-9, miR-122, and miR-141 levels were increased in AP
      patients. These 4 miRNAs may represent diagnostic and prognostic biomarkers for
      AP.

PMID- 29332988
TI  - The Effect of Jaw Position on Perceptual and Acoustic Characteristics of Speech.
AB  - Bite blocks are used to stabilize the jaw and to isolate tongue and lip movements
      from that of the mandible during speech and nonspeech activities. Ten normally
      speaking young adults produced sentences with an unconstrained jaw and with
      unilateral placement of 2-mm and 5-mm bite blocks. Six listeners rated sentences
      spoken without either bite block as the most natural sounding. Spectral
      characteristics of /s/, /?/ and /t/ (sibilant frication and stop bursts) differed
      significantly with than without bite blocks, such that mean spectral energy
      decreased, and variation and skew of spectral energy increased. Spectral kurtosis
      did not change for the group, but 2 participants exhibited highly kurtotic /s/
      spectra without a bite block that normalized with bite blocks. The second formant
      frequency for the high vowel /i/ was lower with bite blocks; there was no
      systematic difference in F2 slope for diphthongs. Segmental and suprasegmental
      timing of speech articulation was not affected significantly by these small bite
      blocks. This study provides support for using small bite blocks to isolate the
      tongue from the jaw without large effects on speech, but cautions that speech is
      likely to sound less natural than when produced with an unconstrained jaw.

PMID- 29332989
TI  - Art Therapy and Cognitive Processing Therapy for Combat-Related PTSD: A
      Randomized Controlled Trial.
AB  - This randomized controlled trial was designed to determine if art therapy in
      conjunction with Cognitive Processing Therapy (CPT) was more effective for
      reducing symptoms of combat posttraumatic stress disorder (PTSD) than CPT alone.
      Veterans (N = 11) were randomized to receive either individual CPT, or individual
      CPT in conjunction with individual art therapy. PTSD Checklist-Military Version
      and Beck Depression Inventory-II scores improved with treatment in both groups
      with no significant difference in improvement between the experimental and
      control groups. Art therapy in conjunction with CPT was found to improve trauma
      processing and veterans considered it to be an important part of their treatment
      as it provided healthy distancing, enhanced trauma recall, and increased access
      to emotions.

PMID- 29332990
TI  - Order preservation of expected information content using Unscented Transform
      approximation of multivariate prior distributions in HIV 2-LTR experiment design.
AB  - Numerical computation of the expected information content of a prospective
      experimental design is computationally expensive, requiring calculating the
      Kullback-Leibler divergence of the posterior distribution from the prior for
      simulated data from a large sample of points from the prior distribution. In this
      work, we investigate whether the Unscented Transform (UT) of the prior
      distribution can provide an adequate estimate of the expected information content
      in the context of experiment design for a previously validated HIV-1 2-LTR model.
      Three different schedules with evenly distributed time points have been used to
      generate the experimental data along with the incorporation of qPCR noise for the
      study. The UT shows promise in estimating information content by preserving the
      optimal ordering of 2-LTR sample collection schedules, when compared to
      completely stochastic sampling from the underlying multivariate distributions.

PMID- 29332991
TI  - Prospective HIV Clinical Trial Comparison by Expected Kullback-Leibler
      Divergence.
AB  - The sample frequency and volume of blood that can be drawn from a single patient
      is meticulously restricted under the human subject protection protocols
      established by an institutional review board (IRB). Consequently, the amount of
      samples that can be taken during a particular experiment is limited. In order to
      ensure an effective experiment design, considerations must be taken choosing when
      to take patient samples. A validated model of HIV-1 viral replication and 2-LTR
      production is exploited to find sub-optimal sampling schedules that maximize
      information content of the experiment outcome. This is done through a Forward
      Stepwise Regression (FSR) process with Kullback Liebler Divergence (KLD) as a
      selection criterion. Suboptimal schedules are found for an experiment taking four
      sample points over a possible span of 20 weeks. All schedules found with the FSR
      process contain significantly more information than both a uniform schedule and a
      schedule used in a previous experiment with 4 sample points. This work
      demonstrates the advantages of using KLD as a tool in the experiment design
      process to increase information content.

PMID- 29332992
TI  - Experiment Design for Early Molecular Events in HIV Infection.
AB  - The recent introduction of integrase inhibitors to the HIV antiviral repertoire
      permits us to create in vitro experiments that reliably terminate HIV infection
      at the point of chromosomal integration. This allows us to isolate the dynamics
      of a single round of infection, without needing to account for the influence of
      multiple overlapping rounds of infection. By measuring the various nucleic acid
      concentrations in a population of infected target cells at multiple time points,
      we can infer the rates of these molecular events with great accuracy, which
      allows us to compare the rates between target cells with different functional
      phenotypes. This information will help in understanding the behavior of the
      various populations of reservoir cells such as active and quiescent T-cells which
      maintain HIV infection in treated patients. In this paper, we introduce a family
      of models of the early molecular events in HIV infection, with either linear
      dynamics or age-structured delays at each step. We introduce an experimental
      design metric based on the delta AIC (Akaike Information Criteria) between a
      model fit for simulated data from a matching model vs a mismatched model, which
      allows us to determine a candidate experiment design's ability to discriminate
      between models. Using parameters values drawn from experimentally-derived priors
      corrupted with appropriate measurement noise, we confirm that a proposed sampling
      schedule at different time points allows us to consistently discriminate between
      candidate models.

PMID- 29332993
TI  - Composition of the C6+ Fraction of Natural Gas by Multiple Porous Layer Open
      Tubular Capillaries Maintained at Low Temperatures.
AB  - As the sources of natural gas become more diverse, the trace constituents of the
      C6+ fraction are of increasing interest. Analysis of fuel gas (including natural
      gas) for compounds with more than 6 carbon atoms (the C6+ fraction) has
      historically been complex and expensive. Hence, this is a procedure that is used
      most often in troubleshooting rather than for day-to-day operations. The C6+
      fraction affects gas quality issues and safety considerations such as anomalies
      associated with odorization. Recent advances in dynamic headspace vapor
      collection can be applied to this analysis and provide a faster, less complex
      alternative for compositional determination of the C6+ fraction of natural gas.
      Porous layer open tubular capillaries maintained at low temperatures (PLOT-cryo)
      form the basis of a dynamic headspace sampling method that was developed at NIST
      initially for explosives in 2009. This method has been recently advanced by the
      combining of multiple PLOT capillary traps into one "bundle," or wafer, resulting
      in a device that allows the rapid trapping of relatively large amounts of
      analyte. In this study, natural gas analytes were collected by flowing natural
      gas from the laboratory (gas out of the wall) or a prepared surrogate gas flowing
      through a chilled wafer. The analytes were then removed from the PLOT-cryo wafer
      by thermal desorption and subsequent flushing of the wafer with helium. Gas
      chromatography (GC) with mass spectrometry (MS) was then used to identify the
      analytes.

PMID- 29332994
TI  - Application of the Advanced Distillation Curve Method to the Comparison of Diesel
      Fuel Oxygenates: 2,5,7,10-Tetraoxaundecane (TOU), 2,4,7,9-Tetraoxadecane (TOD),
      and Ethanol/Fatty Acid Methyl Ester (FAME) Mixtures.
AB  - Although they are amongst the most efficient engine types, compression-ignition
      engines have difficulties achieving acceptable particulate emission and NOx
      formation. Indeed, catalytic after-treatment of diesel exhaust has become common
      and current efforts to reformulate diesel fuels have concentrated on the
      incorporation of oxygenates into the fuel. One of the best ways to characterize
      changes to a fuel upon the addition of oxygenates is to examine the volatility of
      the fuel mixture. In this paper, we present the volatility, as measured by the
      advanced distillation curve method, of a prototype diesel fuel with novel diesel
      fuel oxygenates: 2,5,7,10-tetraoxaundecane (TOU), 2,4,7,9-tetraoxadecane (TOD),
      and ethanol/fatty acid methyl ester (FAME) mixtures. We present the results for
      the initial boiling behavior, the distillation curve temperatures, and track the
      oxygenates throughout the distillations. These diesel fuel blends have several
      interesting thermodynamic properties that have not been seen in our previous
      oxygenate studies. Ethanol reduces the temperatures observed early in the
      distillation (near ethanol's boiling temperature). After these early distillation
      points (once the ethanol has distilled out), B100 has the greatest impact on the
      remaining distillation curve and shifts the curve to higher temperatures than
      what is seen for diesel fuel/ethanol blends. In fact, for the 15% B100 mixture
      most of the distillation curve reaches temperatures higher than those seen diesel
      fuel alone. In addition, blends with TOU and TOD also exhibited uncommon
      characteristics. These additives are unusual because they distill over most the
      distillation curve (up to 70%). The effects of this can be seen both in
      histograms of oxygenate concentration in the distillate cuts and in the
      distillation curves. Our purpose for studying these oxygenate blends is
      consistent with our vision for replacing fit-for-purpose properties with
      fundamental properties to enable the development of equations of state that can
      describe the thermodynamic properties of complex mixtures, with specific
      attention paid to additives.

PMID- 29332995
TI  - On the Functional Form of Temporal Discounting: An Optimized Adaptive Test.
AB  - The tendency to discount the value of future rewards has become one of the best
      studied constructs in the behavioral sciences. Although hyperbolic discounting
      remains the dominant quantitative characterization of this phenomenon, a variety
      of models have been proposed and consensus around the one that most accurately
      describes behavior has been elusive. To help bring some clarity to this issue, we
      propose an Adaptive Design Optimization (ADO) method for fitting and comparing
      models of temporal discounting. We then conduct an ADO experiment aimed at
      discriminating among six popular models of temporal discounting. Rather than
      supporting a single underlying model, our results show that each model is
      inadequate in some way to describe the full range of behavior exhibited across
      subjects. The precision of results provided by ADO further identify specific
      properties of models, such as accommodating both increasing and decreasing
      impatience, that are mandatory to describe temporal discounting broadly.

PMID- 29332996
TI  - Optimal Population and Exhaustible Resource Constraints.
AB  - A large literature considers the optimal size and growth rate of the human
      population, trading off the utility value of additional people with the costs of
      a larger population. In this literature, an important parameter is the social
      weight placed on population size; a standard result is that a planner with a
      larger weight on population chooses larger population levels and growth rates. We
      demonstrate that this result is conditionally overturned when an exhaustible
      resource constraint is introduced: if the discount rate is small enough, the
      optimal population today decreases with the welfare weight on population size.
      That is, a more total-utilitarian social planner could prefer a smaller
      population today than a more average-utilitarian social planner. We also present
      a numerical illustration applied to the case of climate change, where we show
      that under plausible real-world parameter values, our result matters for the
      direction and magnitude of optimal population policy.

PMID- 29332997
TI  - EPR UNIFORM FIELD SIGNAL ENHANCEMENT BY DIELECTRIC TUBES IN CAVITIES.
AB  - The dielectric tube resonator (DTR) for EPR spectroscopy is introduced. It is
      defined as a metallic cylindrical TE011 microwave cavity that contains a
      dielectric tube centered on the axis of the cylinder. Contour plots of dimensions
      of the metallic cylinder to achieve resonance at 9.5 GHz are shown for quartz,
      sapphire, and rutile tubes as a function of wall thickness and average radius.
      These contour plots were developed using analytical equations and confirmed by
      finite element modeling. They can be used in two ways: design of the metallic
      cylinder for use at 9.5 GHz that incorporates a readily available tube such as a
      sapphire tube intended for NMR, or design of a custom procured tube for optimized
      performance for specific sample-size constraints. The charts extend to the
      limiting condition where the dielectric fills the tube. However, the structure at
      this limit is not a dielectric resonator due to the metal wall and does not
      radiate. In addition, the uniform field (UF) DTR is introduced. Development of
      the UF resonator starting with a dielectric tube resonator is shown. The diameter
      of the tube remains constant along the cavity axis, and the diameter of the
      cylindrical metallic enclosure increases at the ends of the cavity to satisfy the
      uniform field condition. This structure has advantages over the previously
      developed UF TE011 resonators: higher resonator efficiency parameter Lambda,
      convenient overall size when using sapphire tubes, and higher quality data for
      small samples. The DTR and UF DTR structures fill the gap between free space and
      dielectric resonator limits in a continuous manner.

PMID- 29332998
TI  - High-pressure EPR spectroscopy studies of the E. coli lipopolysaccharide
      transport proteins LptA and LptC.
AB  - The use of pressure is an advantageous approach to the study of protein structure
      and dynamics because it can shift the equilibrium populations of protein
      conformations toward higher energy states that are not of sufficient population
      to be observable at atmospheric pressure. Recently, the Hubbell group at the
      University of California, Los Angeles, reintroduced the application of high
      pressure to the study of proteins by electron paramagnetic resonance (EPR)
      spectroscopy. This methodology is possible using X-band EPR spectroscopy due to
      advances in pressure intensifiers, sample cells, and resonators. In addition to
      the commercial availability of the pressure generation and sample cells by
      Pressure Biosciences Inc., a five-loop-four-gap resonator required for the
      initial high pressure EPR spectroscopy experiments by the Hubbell group, and
      those reported here, was designed by James S. Hyde and built and modified at the
      National Biomedical EPR Center. With these technological advances, we determined
      the effect of pressure on the essential periplasmic lipopolysaccharide (LPS)
      transport protein from Escherichia coli, LptA, and one of its binding partners,
      LptC. LptA unfolds from the N-terminus to the C-terminus, binding of LPS does not
      appreciably stabilize the protein under pressure, and monomeric LptA unfolds
      somewhat more readily than oligomeric LptA upon pressurization to 2 kbar. LptC
      exhibits a fold and relative lack of stability upon LPS binding similar to LptA,
      yet adopts an altered, likely monomeric, folded conformation under pressure with
      only its C-terminus unraveling. The pressure-induced changes likely correlate
      with functional changes associated with binding and transport of LPS.

PMID- 29332999
TI  - An integrated electrolysis - electrospray - ionization antimicrobial platform
      using Engineered Water Nanostructures (EWNS) for food safety applications.
AB  - Engineered water nanostructures (EWNS) synthesized utilizing electrospray and
      ionization of water, have been, recently, shown to be an effective, green,
      antimicrobial platform for surface and air disinfection, where reactive oxygen
      species (ROS), generated and encapsulated within the particles during synthesis,
      were found to be the main inactivation mechanism. Herein, the antimicrobial
      potency of the EWNS was further enhanced by integrating electrolysis,
      electrospray and ionization of de-ionized water in the EWNS synthesis process.
      Detailed physicochemical characterization of these enhanced EWNS (eEWNS) was
      performed using state-of-the-art analytical methods and has shown that, while
      both size and charge remain similar to the EWNS (mean diameter of 13 nm and
      charge of 13 electrons), they possess a three times higher ROS content. The
      increase of the ROS content as a result of the addition of the electrolysis step
      before electrospray and ionization led to an increased antimicrobial ability as
      verified by E. coli inactivation studies using stainless steel coupons. It was
      shown that a 45-minute exposure to eEWNS resulted in a 4-log reduction as opposed
      to a 1.9-log reduction when exposed to EWNS. In addition, the eEWNS were assessed
      for their potency to inactivate natural microbiota (total viable and yeast and
      mold counts), as well as, inoculated E.coli on the surface of fresh organic
      blackberries. The results showed a 97% (1.5-log) inactivation of the total viable
      count, a 99% (2-log) reduction in the yeast and mold count and a 2.5-log
      reduction of the inoculated E.coli after 45 minutes of exposure, without any
      visual changes to the fruit. This enhanced antimicrobial activity further
      underpins the EWNS platform as an effective, dry and chemical free approach
      suitable for a variety of food safety applications and could be ideal for
      delicate fresh produce that cannot withstand the classical, wet disinfection
      treatments.

PMID- 29333000
TI  - Distributions of emissions intensity for individual beef cattle reared on pasture
      based production systems.
AB  - Life Cycle Assessment (LCA) of livestock production systems is often based on
      inventory data for farms typical of a study region. As information on individual
      animals is often unavailable, livestock data may already be aggregated at the
      time of inventory analysis, both across individual animals and across seasons.
      Even though various computational tools exist to consider the effect of genetic
      and seasonal variabilities in livestock-originated emissions intensity, the
      degree to which these methods can address the bias suffered by representative
      animal approaches is not well-understood. Using detailed on-farm data collected
      on the North Wyke Farm Platform (NWFP) in Devon, UK, this paper proposes a novel
      approach of life cycle impact assessment that complements the existing LCA
      methodology. Field data, such as forage quality and animal performance, were
      measured at high spatial and temporal resolutions and directly transferred into
      LCA processes. This approach has enabled derivation of emissions intensity for
      each individual animal and, by extension, its intra-farm distribution, providing
      a step towards reducing uncertainty related to agricultural production inherent
      in LCA studies for food. Depending on pasture management strategies, the total
      emissions intensity estimated by the proposed method was higher than the
      equivalent value recalculated using a representative animal approach by 0.9-1.7
      kg CO2-eq/kg liveweight gain, or up to 10% of system-wide emissions. This finding
      suggests that emissions intensity values derived by the latter technique may be
      underestimated due to insufficient consideration given to poorly performing
      animals, whose emissions becomes exponentially greater as average daily gain
      decreases. Strategies to mitigate life-cycle environmental impacts of pasture
      based beef productions systems are also discussed.

PMID- 29333001
TI  - Evidence for the Involvement of Lipid Rafts and Plasma Membrane Sphingolipid
      Hydrolases in Pseudomonas aeruginosa Infection of Cystic Fibrosis Bronchial
      Epithelial Cells.
AB  - Cystic fibrosis (CF) is the most common autosomal genetic recessive disease
      caused by mutations of gene encoding for the cystic fibrosis transmembrane
      conductance regulator. Patients with CF display a wide spectrum of symptoms, the
      most severe being chronic lung infection and inflammation, which lead to onset of
      cystic fibrosis lung disease. Several studies indicate that sphingolipids play a
      regulatory role in airway inflammation. The inhibition and downregulation of
      GBA2, the enzyme catabolizing glucosylceramide to ceramide, are associated with a
      significant reduction of IL-8 production in CF bronchial epithelial cells.
      Herein, we demonstrate that GBA2 plays a role in the proinflammatory state
      characterizing CF cells. We also report for the first time that Pseudomonas
      aeruginosa infection causes a recruitment of plasma membrane-associated
      glycosphingolipid hydrolases into lipid rafts of CuFi-1-infected cells. This
      reorganization of cell membrane may be responsible for activation of a signaling
      cascade, culminating in aberrant inflammatory response in CF bronchial epithelial
      cells upon bacterial infection. Taken together, the presented data further
      support the role of sphingolipids and their metabolic enzymes in controlling the
      inflammatory response in CF.

PMID- 29333003
TI  - Histopathological study of gallbladder carcinoma and its mimics with role of
      carcinoembryonic antigen immunomarker in resolving diagnostic difficulties.
AB  - Background: Gallbladder carcinoma (GBC) sometimes presents with nonspecific
      signs, without forming a mass, mimicking benign gallbladder (GB) diseases. On the
      contrary, benign GB diseases may mimic GBC. Material and Methods: We
      retrospectively reviewed 107 cases over a period of 3 years (May 2012-April
      2015), which included 41 review cases and 66 departmental cases. Carcinoembryonic
      antigen (CEA) immunomarker expression was done. Results: In 27 of the 41 review
      cases, the diagnoses were benign diseases of GB associated with mild-to-moderate
      dysplasia of mucosal glands; however, after review in our department, it was
      found that of these 27 cases, nine cases were actually well-differentiated
      adenocarcinoma of GB with diffuse CEA expression and were mis diagnosed as benign
      diseases of GB with dysplasia. In 32 out of 66 departmental cases, initial
      histopathological diagnoses were benign diseases of GB associated with dysplastic
      mucosal glands. After CEA staining, 11 out of these 32 cases turned out to be
      adenocarcinoma of the GB. Among the rest 34 (34/66) departmental primary GBC
      cases, no CEA expression was seen in six cases, focal expression was seen in 12
      cases, and diffuse expression was seen in 16 cases. No diffuse CEA expression was
      seen in benign diseases of the GB with dysplasia. Conclusion: GBC sometimes may
      not be diagnosed radiologically and grossly as it often presents without any mass
      and specific signs, which lead to under diagnosis. Some benign cases may mimic
      GBC and may complicate histological diagnosis. CEA expression may aid as an
      additional diagnostic aid in resolving diagnostic dilemmas.

PMID- 29333004
TI  - DROSHA rs642321 Polymorphism Influence Susceptibility to Childhood Acute
      Lymphoblastic Leukemia: A Preliminary Report.
AB  - Introduction: It has been well known that the microRNA biogenesis is involved in
      the pathogenesis of various diseases. We investigated the possible association
      between DROSHA rs642321 variant and risk of acute lymphocytic leukemia (ALL).
      Materials and Methods: We genotyped 75 children diagnosed with ALL and 115 age-
      and sex-matched children with no history of cancer of any type (as the control
      group) by the tetra amplification refractory mutation system-polymerase chain
      reaction. Results: We found that DROSHA rs642321 C > T variant significantly
      decreased the risk of ALL in codominant (TT vs. CC: odds ratio [OR] = 0.33, 95%
      confidence interval [CI] = 0.14-0.80, P = 0.020) and dominant (TT + CT vs. CC: OR
      = 0.51, 95% CI = 0.27-0.94, P = 0.037) inheritance model tested. The rs642321 T
      allele was associated with protective against ALL (OR = 0.58, 95% CI = 0.38-0.88,
      P = 0.011) in comparison with C allele. Conclusion: The study findings revealed
      that DROSHA rs642321 variant decreased the risk of pediatrics ALL in an Iranian
      population. Larger sample sizes with different ethnicities are needed to validate
      our findings.

PMID- 29333005
TI  - Prognostic Factors and Survival Outcomes of Intracranial Ependymoma Treated with
      Multimodality Approach.
AB  - Objectives: We aimed to analyze treatment outcomes of intracranial ependymoma
      (ICE) treated at our institute with multimodality approach. Materials and
      Methods: Demography, treatment details, and survival data of 40 patients (2005
      2012) were collected in a predesigned pro forma. Kaplan Meier method was used to
      analyze disease-free survival (DFS) and the impact of prognostic factors was
      determined using univariate analysis (log-rank test). Multivariate analysis was
      performed using Cox-proportional hazard model. SPSS version 21.0 was used for all
      statistical analysis. Results: Male:female ratio was 29:11. Gross total
      resection: subtotal resection or less was 42.5%: 57.5%. A total of 16 patients
      (40%) had anaplastic histology. All except two patients received adjuvant
      radiotherapy. Four patients received concurrent chemotherapy (temozolomide [TMZ])
      and 10 patients received adjuvant chemotherapy (6 carboplatin plus etoposide; 4
      TMZ). Median follows up was 18 months (2-60 months). Median DFS for the entire
      cohort was 22.42 months. The estimated 1, 2, and 3 years DFS was found to be
      58.5%, 41%, and 30.7%, respectively. On univariate analysis, patients receiving
      higher radiation dose (56 Gray vs. 60 Gray; hazard ratio [HR] 0.366; 95%
      confidence interval [CI] 0.142-0.9553; P = 0.02) and lower MIB labeling index
      (<20 vs. >=20; HR 0.238; 95% CI 0.092-0.617; P = 0.001) had a better DFS. Higher
      radiation dose continued to be an independent prognostic factor on multivariate
      analysis (HR 0.212; 95% CI 0.064-0.856; P = 0.03). Conclusion: ICE has guarded
      prognosis. Adjuvant radiotherapy to a higher radiation dose improves survival.
      Higher MIB labeling index connotes a dismal survival despite the use of
      radiotherapy and chemotherapy.

PMID- 29333002
TI  - S1P Lyase Regulation of Thymic Egress and Oncogenic Inflammatory Signaling.
AB  - Sphingosine-1-phosphate (S1P) is a potent lipid signaling molecule that regulates
      pleiotropic biological functions including cell migration, survival,
      angiogenesis, immune cell trafficking, inflammation, and carcinogenesis. It acts
      as a ligand for a family of cell surface receptors. S1P concentrations are high
      in blood and lymph but low in tissues, especially the thymus and lymphoid organs.
      S1P chemotactic gradients are essential for lymphocyte egress and other aspects
      of physiological cell trafficking. S1P is irreversibly degraded by S1P lyase
      (SPL). SPL regulates lymphocyte trafficking, inflammation and other physiological
      and pathological processes. For example, SPL located in thymic dendritic cells
      acts as a metabolic gatekeeper that controls the normal egress of mature T
      lymphocytes from the thymus into the circulation, whereas SPL deficiency in gut
      epithelial cells promotes colitis and colitis-associated carcinogenesis (CAC).
      Recently, we identified a complex syndrome comprised of nephrosis, adrenal
      insufficiency, and immunological defects caused by inherited mutations in human
      SGPL1, the gene encoding SPL. In the present article, we review current evidence
      supporting the role of SPL in thymic egress, inflammation, and cancer. Lastly, we
      summarize recent progress in understanding other SPL functions, its role in
      inherited disease, and SPL targeting for therapeutic purposes.

PMID- 29333006
TI  - Rational Use of Imaging to Stage Breast Cancer: Evidences for a Selective
      Approach.
AB  - Introduction: Staging investigations at diagnosis are customary to accurately
      assign a clinical stage before therapy. The practice of routine imaging in
      patients asymptomatic for metastasis is not recommended but widely adopted. This
      study was done to reexamine the basis behind guideline recommendations and to
      identify the factors predictive of asymptomatic metastasis. Methods: Oncology
      records of 200 breast cancer patients in clinical Stages I-III at diagnosis were
      prospectively reviewed. Baseline demographic information, tumor characteristics,
      and pathological data including molecular typing were collected. The prevalence
      of metastasis deduced and accuracy of bone scan, chest X-ray (CXR), liver
      ultrasound, and computed tomography (CT) chest analyzed. Patient and tumor
      characteristics predictive of asymptomatic metastasis tested for significance
      using appropriate statistical tests. Results: The prevalence of asymptomatic
      metastasis was 13.5%. Bone lesions (8%) were the most common metastatic site
      followed by lungs (7%) and liver (1%). Sensitivity, specificity, positive- and
      negative-predictive values of bone scans and CT chest were 100%, 97%, 74%, 100%,
      and 92%, 99%, 87, 3%, 99.4%, respectively. The above values for ultrasound
      abdomen and CXRs were 100%, 99%, 93%, 100% and 21%, 94%, 20%, 94%, respectively.
      Tumor size (P = 0.001), tumor Stage T1/T2 versus T3/T4 (P = 0.0002), nodal stages
      N0/N1 versus N2/N3 (P = 0.001), high histological Grade G I versus GII/GIII (P =
      0.0001) and molecular types were strongly predictive of metastatic disease.
      Conclusion: The routine use of imaging to detect distant metastasis in
      asymptomatic patients is not recommended in newly diagnosed breast cancer. A
      selective approach may be adopted in individuals with tumor more than 5 cm,
      advanced nodal disease, higher histological grade, and aggressive molecular
      types.

PMID- 29333007
TI  - Utility of Cluster of Differentiation 5 and Cluster of Differentiation 117
      Immunoprofile in Distinguishing Thymic Carcinoma from Pulmonary Squamous Cell
      Carcinoma: A Study on 1800 Nonsmall Cell Lung Cancer Cases.
AB  - Background: Mediastinum harbors a mixed bag of neoplastic lesions with varied
      therapeutic and prognostic implications. Distinguishing pulmonary squamous cell
      carcinoma from thymic carcinoma is a challenging task owing to rather nonspecific
      clinicoradiological features and a considerable overlap in histomorphological
      features. Thus, we evaluated the diagnostic utility of cluster of differentiation
      5 (CD5) and CD117 immunohistochemical markers in distinguishing these tumors.
      Materials and Methods: The archives of department of histopathology were
      retrospectively reviewed from June 2012 to May 2016. Formalin-fixed paraffin
      embedded blocks of 1800 cases diagnosed as nonsmall cell lung carcinoma were
      retrieved, and immunohistochemical expression of CD5 and CD117 was evaluated in
      these cases. Results: Adenocarcinoma (980; 54.44%) was the most common
      histological subtype of lung carcinoma observed in our study. CD117 was positive
      in 171 out of 1800 cases (9.5%) of which 120 cases (70.17%) were adenocarcinoma,
      followed by 40 cases (23.4%) of squamous cell carcinoma. Immunoreactivity for CD5
      was observed in 209 cases (11.61%), 200 (95.7%) cases of which were diagnosed as
      adenocarcinoma. None of the cases diagnosed as squamous cell carcinoma on
      histomorphology showed CD5 immunoexpression. Conclusion: While thymic squamous
      cell carcinomas are well known for CD5 and CD117 coexpression, none of the cases
      of squamous cell carcinoma arising in lung express CD5. These markers are a
      diagnostic tool to distinguish a primary lung squamous cell carcinoma from thymic
      carcinoma, particularly in the setting of a central pulmonary lesion with
      mediastinal involvement.

PMID- 29333009
TI  - Peripheral and Central Giant Cell Lesions in Children: Institutional Experience
      at Subharti Dental College and Hospital.
AB  - Introduction: Giant cell lesions (GCG) are a group of varied lesions that contain
      a multitude of multinucleated, osteoclast like giant cells within connective
      tissue stroma. These include giant cell granulomas which may be central (CGCG),
      if they lie within the jaw bone, or, peripheral (PGCG) if they lie within the
      soft tissue. Giant cell granulomas comprised 9.29% of all oral lesions. This case
      series comprises of 5 giant cell lesions in children between the ages of 4 to 12
      years. Materials and Methods: A retrospective analysis was conducted of all
      patients who were diagnosed with giant cell lesions and treated over a period of
      10 years (from August 2004 to August 2014) at Subharti Dental College and
      Hospital, Meerut, India. Results: A total of 5 giant cell lesions were identified
      in this case series, of which 2 cases were diagnosed as PGCG and 3 cases as CGCG.
      Surgical excision and curettage was performed for 2 peripheral lesions under
      local anesthesia while 1 central lesion was excised under general anesthesia. Two
      central lesions were treated with a non-surgical approach using intralesional
      corticosteroid. Conclusion: Our experience suggests that a correct diagnosis and
      complete surgical excision with curettage is effective in complete management of
      oral giant cell lesions in the pediatric age group.

PMID- 29333008
TI  - Metabolic Syndrome and Breast Cancer Risk.
AB  - Objective: The study was meant to estimate the prevalence of metabolic syndrome
      in patients with breast cancer and to establish its role as an independent risk
      factor on occurrence of breast cancer. Materials and Methods: Fifty women aged
      between 40 and 80 years with breast cancer and fifty controls of similar age were
      assessed for metabolic syndrome prevalence and breast cancer risk factors,
      including age at menarche, reproductive status, live births, breastfeeding, and
      family history of breast cancer, age at diagnosis of breast cancer, body mass
      index, and metabolic syndrome parameters. Results: Metabolic syndrome prevalence
      was found in 40.0% of breast cancer patients, and 18.0% of those in control group
      (P = 0.02). An independent and positive association was seen between metabolic
      syndrome and breast cancer risk (odds ratio = 3.037; 95% confidence interval
      1.214-7.597). Conclusions: Metabolic syndrome is more prevalent in breast cancer
      patients and is an independent risk factor for breast cancer.

PMID- 29333010
TI  - Sinusoidal Obstruction Syndrome during Treatment for Wilms' Tumor: A Life
      threatening Complication.
AB  - Context: Survival rates exceed 90% in Wilms' tumor (WT). Actinomycin-D (ACT-D)
      which is indispensable in the management of WT is associated with the development
      of sinusoidal obstruction syndrome (SOS), a potentially fatal complication. Aims:
      The aim is to study the presentation, management, and outcome of SOS complicating
      ACT-D administration in WT. Settings and Design: Retrospective file review
      conducted in a Pediatric Hematology-Oncology unit. Materials and Methods:
      Patients diagnosed and treated for WT from January 2012 to December 2015 were
      analyzed. SOS was diagnosed clinically, based on McDonalds criteria, requiring
      two of the following: jaundice, hepatomegaly and/or right upper quadrant pain,
      weight gain with or without ascites. Results: Of 104 patients treated, SOS
      occurred in 5 (4.8%). Age: 6 months to 5 years, 3 were girls. Tumor involved left
      kidney in 3, right in 1 and a horseshoe kidney in 1. Histopathology was
      consistent with WT in 4 and clear cell sarcoma kidney in 1. One had pulmonary
      metastases. Three developed SOS preoperatively and two during adjuvant
      chemotherapy. None received radiotherapy. Clinical manifestations comprised of
      jaundice, hepatomegaly, ascites/weight gain, respiratory distress, hypotension,
      and encephalopathy. Laboratory findings included thrombocytopenia, elevated serum
      transaminases, and coagulopathy. Treatment included fluid restriction, broad
      spectrum antibiotics, and transfusional support. Two children received N-acetyl
      cysteine infusion. Defibrotide was administered to two patients. Four recovered
      and one succumbed to multi-organ failure. Two patients were safely re-challenged
      with 50% doses of ACT-D. Conclusions: SOS is a clinical diagnosis. Systematic
      supportive care can enable complete recovery. Under close monitoring, re
      challenge of ACT-D can be performed in gradually escalating doses.

PMID- 29333011
TI  - Oral Verrucous Carcinoma: Ten Year Experience from a Tertiary Care Hospital in
      India.
AB  - Background: Verrucous carcinoma of the oral cavity (OVC) is an uncommon variant
      of oral squamous cell carcinoma (OSCC). The clinical presentation and surgical
      outcomes of OVC are unique; however, the management protocols for OVC are largely
      extrapolated from OSCC. Objectives: The aim is to study the clinical,
      histopathological demographics, and outcome of OVC at a tertiary care referral
      hospital in South India. To study the need for lymph node dissection and the role
      of adjuvant therapy for close resection margins. Materials and Methods: A
      retrospective review of all patients diagnosed to have OVC between January 2005
      and April 2015 was undertaken. Data were collected from hospital records and
      telephonic interview when possible. Results: Thirty patients were diagnosed to
      have OVC. The most common site of the presentation was the buccal mucosa. Twenty
      three patients had wide local excision of the primary tumor and seven patients
      had neck dissection as well. None of the patients who underwent neck dissection
      had node-positive disease pathologically. The margins were considered close in
      nine patients, only one of these patients received adjuvant radiation therapy;
      despite among the patients with close resection margins, there was no recurrence
      or disease-related mortality. Among the thirty patients, there was only one
      patient who had recurred locally and there was no disease associated mortality.
      Conclusions: OVC is a unique variant of OSCC which has a good prognosis. Routine
      lymphadenectomy can be avoided.

PMID- 29333012
TI  - Squamous Cell Carcinoma Lung with Skeletal Muscle Involvement: A 8-year Study of
      a Tertiary Care Hospital in Kashmir.
AB  - Aims: Lung cancer is the most common malignancy throughout the world. Nonsmall
      cell lung cancer (NSCLC) is the most common type, and squamous cell type is most
      common in India. Mostly, patients present with chest-related symptoms and signs.
      Isolated skeletal muscle metastasis (ISMM) is rarely seen. The aim was to see
      muscle metastasis and its prognosis. Materials and Methods: We are presenting our
      data of 8 years about this common malignancy with relation to muscle metastasis,
      either alone or with other system metastasis. Results: Muscle metastasis is seen
      1.5% of patients, with male: female of 8:1. Overall median survival was 15 months
      and progression-free survival was 12 months. Conclusion: One peculiarity seen was
      ISMM with no pulmonary system and severe paraneoplastic hypercalcemia. Local
      therapy may be having an impact on overall survival in metachronous muscle
      involvement.

PMID- 29333013
TI  - Comparative Study of Imprint Cytology and Histopathology of Soft Tissue Tumors.
AB  - Background: The components of soft tissue are fibroblasts, collagen, vascular
      structures, fatty tissue, skeletal muscles, smooth muscles, and neural tissue.
      The real incidence of soft tissue tumors (STTs) is difficult to estimate because
      most of them are benign (Benign: Malignant-100:1). Aims: The aim of the present
      study was undertaken to note the patterns of presentation of patients with STTs
      and to evaluate the findings of imprint cytology (IC) and histopathological
      examination (HPE) of STTs. Materials and Methods: The present study was
      undertaken for 1 year. A total of 41 patients with clinically and radiologically
      diagnosed STTs were included in the study. Following surgery, imprint smear was
      taken for each tumor, before delivering the tissue to 10% formalin. HPE was
      subsequently performed. Results: The age of the patients ranged from 4 months to
      80 years with a mean of 35.6 +/- 17.5 years. The ratio of males to females was
      1.05:1. HPE revealed that 21 (51.2%) tumors were benign and 20 (48.8%) malignant.
      Imprint smears revealed 16 (39%) tumors to be benign and 20 (48.8%) malignant. IC
      was inconclusive in 5 (12.2%) cases. The sensitivity of IC was found to be 89.5%
      and specificity 82.35%. The positive predictive value of IC was 85%. The accuracy
      of IC for diagnosis of both benign and malignant tumors was found to be 75%.
      Conclusion: IC of STTs is a rapid and simple method of intraoperative diagnosis,
      and it can serve as a viable alternative to frozen section biopsy, particularly
      in rural settings.

PMID- 29333014
TI  - Is Colorectal Cancer in Young (<40 Years) Different from those in the Elderly
      (>40 Years): Experience from a Regional Care Center.
AB  - Background: Colorectal cancer (CRC) is considered a disease of elderly. There has
      been a steady decrease in the incidence in those aged >50 years, with an alarming
      increase noted in adults aged <50 years. Subjects and Methods: We retrospectively
      analyzed 89 patients diagnosed with CRC aged <40 years between the years 2010 and
      2014. Their clinical profile, treatment, and outcomes were studied. Results: The
      median age was 33 years with a male preponderance (56.2%). Most common symptoms
      were lower gastrointestinal bleed (48.3%) followed by abdominal pain (46.1%).
      Most common sites were rectum (50.6%) followed by colon. Histology in all was
      adenocarcinoma. Most tumors were moderately differentiated (54%) and were stage 4
      (36%). Most common sites of metastases were liver (46.9%) followed by peritoneum
      and ovaries. Majority underwent surgery with adjuvant chemotherapy, with/without
      radiotherapy. Chemotherapy was administered in 70 patients, majority receiving
      FOLFOX-4 regimen (88.6%). Median survival was 23 months. Survival in early
      stage[1],[2] was significantly higher than in advanced stages (3 and above), 34
      and 19 months (P = 0.0287), in those aged >40 years compared to <40-35 versus 23
      months (P = 0.0029), nonmetastatic compared to metastatic disease - 26 versus 14
      months (P = 0.00196), and females compared to males - 26 and 18 months (P =
      0.0242). There was no significant difference in survival with respect to tumor
      grade or site of metastases (hepatic versus extrahepatic). Conclusions:
      Colorectal carcinoma in young seems to be an emerging problem in India. Any young
      patient presenting with symptoms suggestive of a colonic malignancy should be
      evaluated promptly and treated aggressively.

PMID- 29333015
TI  - A Profile of Pediatric Solid Tumors: A Single Institution Experience in Kashmir.
AB  - Aims: The purpose of this retroprospective study was to study the epidemiological
      characteristics and outcomes of children with solid tumors at our institution.
      Subjects and Methods: Three hundred and three pediatrics patients registered at
      Regional Cancer Centre (RCC), Sher-i-Kashmir Institute of Medical Sciences
      (SKIMS), Srinagar, Kashmir, between January 2008 and June 2014, were analyzed
      with regard to demographic status, presenting complaints, investigations,
      treatment, morbidity, and outcomes. Standard statistical methods were used for
      analysis. Results: Among 19,880 patients registered at RCC, SKIMS from January
      2008 till June 2014, 986 (4.9%) were of pediatric age group. Of these, 303
      (30.7%) patients had pediatric solid tumors. The male-to-female ratio was 1.04,
      there were no infants (up to 27 days), 6% were infants and toddlers (28 days-23
      months), 39% were children (2-11 years), and 55% were adolescents (12-19 years).
      There were 86% rural patients and 14% urban patients. Most common were central
      nervous system tumors (25.74%), followed by germ cell tumors (14.52%), primitive
      neuroectodermal tumor/Ewing sarcoma (13.86%), Wilms' tumor (8.9%), osteosarcoma
      (6.6%), rhabdomyosarcoma (5.6%), colorectal cancer (5.28%), neuroblastoma (4.9%),
      and retinoblastoma (2.6%). Outcomes: 33.9% patients went into remission, 35.64%
      were defaulters, 2.97% had stable disease, 2.31% had partial response, 20.79%
      expired, and 3.96% were still on treatment. Of all these patients, 5.28% had a
      relapse. Conclusions: Across the series, advanced stage of presentation, a high
      incidence of default and poor follow-up was seen. Multiple interrelated factors
      are responsible for the poorer outlook of childhood cancer in Kashmir.

PMID- 29333016
TI  - Clinicopathological Features and Outcomes in Primary Central Nervous System
      Lymphoma: A 10-year Experience.
AB  - Context: Primary central nervous system lymphoma (PCNSL) is a variant of
      extranodal lymphoma, accounting for 4% of primary central nervous system tumors.
      PCNSL was more common in immunocompetent individuals. International Extranodal
      Lymphoma Study Group (IELSG) scoring was used for prognostication. High-dose
      methotrexate regimens along with radiotherapy improved outcomes in PCNSL. Aims:
      The aim of this study is to analyze the clinical and pathological features,
      progression-free survival (PFS), and overall survival (OS) in patients with
      PCNSL. Materials and Methods: Data of patients with PCNSL between 2005 and 2016
      were retrospectively analyzed. Outcome was analyzed in patients who received
      chemotherapy. GraphPad Prism software for Windows Version 6 was used to plot the
      Kaplan-Meier curves for PFS and OS. Log-rank test was used to calculate P values.
      P < 0.05 was considered as statistically significant. Results: A total of 42
      patients were available for analysis. Of these, 34 patients who received
      chemotherapy were evaluable for outcome parameters. The median age at
      presentation was 46 years (range, 10-75) with male-to-female ratio of 2.2:1. Only
      2 (4.7%) patients were HIV positive. Diffuse large B-cell lymphoma (DLBCL) was
      the most common histology seen in 41 (97.6%) patients. Using IELSG risk scoring,
      scores of 8 (19%), 19 (45.2%), and 15 (35.8%) were stratified into low,
      intermediate, and high risk. The median PFS and OS were 11 months (range, 2-72)
      and 15.9 months (2.4-80.4), respectively. The median OS was 36.2 months (range,
      8.8-72), 15.6 months (2-36), and 6.1 months (2.6-12.7) in low-, intermediate-,
      and high-risk groups, respectively, which was statistically significant (P =
      0.0002). Conclusions: Immunocompetent patients with PCNSL outnumber
      immunocompromised patients. DLBCL was the most common histology, and IELSG risk
      stratification significantly predicts the outcome in PCNSL.

PMID- 29333017
TI  - Correlation of Hormone Receptor and Human Epidermal Growth Factor Receptor-2/neu
      Expression in Breast Cancer with Various Clinicopathologic Factors.
AB  - Background: A significant development in the breast carcinoma management is the
      correlation between the presence of hormone receptors in the tumor and response
      to hormonal therapy and chemotherapy. Human epidermal growth factor receptor
      2/neu (Her-2/neu) overexpression also serves as a very useful parameter to
      predict response to herceptin. Aim of Study: The study was conducted to correlate
      immunohistochemical expression of markers such as estrogen receptor (ER),
      progesterone receptor (PR), and Her-2/neu with various clinicopathologic
      parameters. Materials and Methods: The study included 509 cases of breast
      carcinoma over a period of 5 years (from May 2009 to May 2014).
      Immunohistochemistry (IHC) for ER, PR, and her-2/neu was performed. Results: ER
      positivity was observed in 42.8% (218/509) cases, PR positivity in 31.8%
      (194/509) cases whereas her-2 neu positivity was seen in 40.7% (203/509) cases.
      Triple marker (ER, PR, and Her-2/neu) negative cases were 23.6% (120/509) cases.
      ER and PR expression was found to have a statistically significant correlation
      with tumor grade. Statistically significant correlation was observed between
      tumor size and tumor grade and her-2/neu expression. Her-2/neu expression showed
      statistically significant association with tumor stage. As the tumor grade
      increased, the proportion of triple-negative cases went on increasing, which was
      statistically significant. Conclusion: IHC has an increasingly important
      prognostic role in determination of factors that affect clinicopathologic
      features. Nevertheless, the results of this large series showed different
      patterns of findings with respect to clinicopathologic features.

PMID- 29333018
TI  - Induction Chemotherapy in Technically Unresectable Locally Advanced T4a Oral
      Cavity Squamous Cell Cancers: Experience from a Regional Cancer Center of South
      India.
AB  - Objectives: The present study aimed to investigate the efficacy, toxicity, and
      impact of induction chemotherapy (IC) in technically unresectable T4a oral cavity
      squamous cell cancers (OSCCs). Materials and Methods: Patients diagnosed with
      technically unresectable locally advanced T4a OSCC from January 2013 and November
      2016 at our center, who received 2-3 cycles of IC and then assessed for
      resectability, were reviewed retrospectively. Patients' profile, response rates
      and toxicity of IC, resectability status, and overall survival (OS) were
      evaluated. Statistical analyses were performed using SPSS version 17.0 for
      Windows (SPSS Inc., Chicago, IL, USA). Results: Totally 80 patients received IC,
      and of them 58 (72.5%) were males. Median age at diagnosis was 44 years (range,
      34-62 years). All our patients received IC with doublet regimen. Majority of the
      patients had buccal mucosa cancers (73.8%), followed by gingivobuccal complex
      (21.2%) and oral tongue (5%) primaries. After IC, partial response was achieved
      in 17 (21.3%) patients, stable disease in 49 (61.3%) patients and disease
      progression was noted in 14 (17.4%) patients. Post-IC, resectability was achieved
      in 19 (23.8%) of 80 patients, but 4 of them did not undergo surgery due to
      logistic and personal reasons. The median OS of patients who underwent surgery
      followed by adjuvant local therapy (n = 15) was 16.9 months (95% CI: 15.2-19.8
      months) and for those treated with nonsurgical local therapy (n = 65) was 8.8
      months (95% CI: 6.8-10.6 months) (log-rank P = 0.000). Conclusions: IC had a
      manageable toxicity profile and achieved resectability in 23.8% of our patients
      with technically unresectable T4a OSCC. Patients underwent resection had a
      significantly better median OS than those who received nonsurgical local
      treatment.

PMID- 29333020
TI  - Oxaliplatin-induced Peripheral Neuropathy in South Indian Cancer Patients: A
      Prospective Study in Digestive Tract Cancer Patients.
AB  - Purpose: The aim of the current study is to report our prospective experience on
      the prevalence of oxaliplatin-induced peripheral neuropathy (OXAIPN) in patients
      with digestive tract cancers treated with oxaliplatin-based combination therapy.
      Materials and Methods: A total of 219 patients scheduled to be treated with
      oxaliplatin-based combination therapy were prospectively examined at baseline and
      follow-up during the therapy between November 2014 and December 2016. The
      incidence of acute OXAIPN was measured using a descriptive questionnaire (yes/no
      question) based on sum of number of symptoms present and NCI-CTCAE version 4.03
      was applied to clinically grade the severity of chronic OXAIPN. Results: Acute
      and chronic OXAIPN was found in 108 of 219 (49.3%) and 127 of 219 (58%) patients,
      respectively. Out of 11 acute OXAIPN symptoms, the vast majority of patients
      manifested cold-induced pharyngolaryngeal (63.8%) dysesthesias or perioral
      (61.1%) paresthesias. Development of acute OXAIPN was predictive of subsequent
      development of chronic OXAIPN (P = 0.0001). All the patients received a median
      cumulative dose of 780 mg/m2 (range: 130-1040 mg/m2). There was a significant
      correlation between the patients who received the median cumulative dose and the
      development of chronic OXAIPN. The incidences of OXAIPN in patients with median
      cumulative dose of <=780 mg/m2 was 51/120 (42.5%) and >780 mg/m2 was OXAIPN 76/99
      (76.7%) (P = 0.0001). Conclusion: The current study results demonstrate that the
      vast majority of patients who receive oxaliplatin-based combination chemotherapy
      will manifest acute OXAIPN that may contribute to the development of chronic
      peripheral neuropathy on repeated courses of drug administration.

PMID- 29333019
TI  - Modulated Radiotherapy with Concurrent and Adjuvant Temozolomide for Anaplastic
      Gliomas: Indian Single-center Data.
AB  - Objective: To evaluate early clinical outcome for anaplastic gliomas (AG) treated
      in the era of modulated radiotherapy (RT) and concurrent plus adjuvant
      temozolomide (TMZ) in an Indian setting. Materials and Methods: Fifty-three
      patients with AGs treated with modulated RT and concurrent (95%) and adjuvant TMZ
      (90%) were analyzed. About 80% of patients had Karnofsky performance status (KPS)
      at least 90 with 30% seizure at presentation. Postoperative magnetic resonance
      imaging was available in 65% cases and RT dose was 60 Gy in 30 fractions. First
      posttreatment imaging was performed at 1 month and then at 3 and 6 months post-RT
      and then every 3 months. Kaplan-Meier analysis was used to estimate disease-free
      survival (DFS) and overall survival (OS), and analysis was done using SPSS
      version 18.0. Results: With median follow-up of 25 months, 2-year DFS and OS were
      75% and 88%. There were only 5% symptomatic central nerves system and 8%
      symptomatic hematological toxicities. At the 1st evaluation, 30.4% had complete
      response (CR), at 3 months 40%, and at 6 months 43%. At 6 months, only 4% had
      progressive disease. Forty-six patients were evaluable till the last follow-up
      with and 55% had stable to CR. On univariate analysis for DFS, KPS at
      presentation >90 (P = 0.001) and response at 6 months (P = 0.02) were significant
      and for OS KPS at presentation (P = 0.004) alone. Conclusion: Modulated RT with
      TMZ among Grade III glioma patients resulted in minimum treatment-related
      toxicities and encouraging survival. Molecular prognostic markers will determine
      most favorable groups in future.

PMID- 29333022
TI  - 2017 ASCO Highlights on Gastointestinal Malignancies.

PMID- 29333021
TI  - Efficacy and Safety of Ibrutinib in Indian Patients with Relapsed or Refractory
      Chronic Lymphocytic Leukemia and Mantle Cell Lymphoma: Cases from a Named Patient
      Program.
AB  - Context: This named patient program evaluated the safety and efficacy of
      ibrutinib, a selective inhibitor of Bruton's tyrosine kinase in Indian patients
      with relapsed/refractory chronic lymphocytic leukemia (CLL, with/without
      chromosome 17 deletion [del17p]) and mantle cell lymphoma (MCL). Subjects and
      Methods: The eight enrolled patients (relapsed/refractory CLL: n = 6 [4/6
      patients with del17p] and relapsed/refractory MCL: n = 2) had median age of 55
      years (range, 52-60) and had received a median of 3 (CLL patients) and 4 (MCL
      patients) prior therapies. Patients received once-daily dose of ibrutinib (420
      mg: CLL, 560 mg: MCL). Results: In CLL patients, the median time to response was
      3 months (range, 0.5-7) and five of six patients had partial response (PR)
      whereas one achieved complete response (CR). Median time on treatment was 11.5
      months (range, 8-14); five patients continued treatment and one was recommended
      stem cell transplantation (SCT). Of the two MCL patients, one achieved PR and one
      showed CR and advanced to SCT. In CLL patients, the median (range) hemoglobin
      level improved from 9.8 g/dL (7.2-11) at baseline to 12.0 g/dL (9.5-13.2) and
      median (range) platelet count improved from 150,000 cells/MUL (21,000-195,000) at
      baseline to 190,350 cells/MUL (130,000-394,000) at the time of analysis (July
      2016). Most adverse events (AEs) reported were infections (n = 2). No Grade 3-4
      or serious AEs, dose reductions, or treatment discontinuation due to AEs were
      reported. Conclusions: In this first real-world experience in Indian patients,
      ibrutinib demonstrated therapeutic efficacy in relapsed/refractory CLL
      (with/without del17p) and MCL. Safety results were consistent with the current
      known profile of ibrutinib.

PMID- 29333023
TI  - Nivolumab - Pearls of Evidence.
AB  - Purpose: Nivolumab is one of the most extensively studied immune checkpoint
      inhibitors across various tumor types. In this narrative review, the current
      clinical efficacy and safety data of anti-programmed death-1 (PD-1) nivolumab for
      nonsmall cell lung cancer (NSCLC) and renal cell cancer (RCC) are elucidated.
      Methods: Systematic search was done on Pubmed, Medline, Embase, Web of Knowledge,
      and Cochrane Central through September 2016 for controlled prospective
      interventional studies of nivolumab across two indications - NSCLC and RCC. There
      was heterogeneity at all levels of abstraction; hence, author did not plan to
      provide a meta-analysis, but instead, a narrative elaboration of results
      structured around the conceptual frameworks. Results: Checkpoint receptor PD-1 is
      a negative regulatory molecule expressed by activated T and B lymphocytes.
      Binding of PD-1 to its ligands, programmed death-ligands 1 and 2, results in the
      downregulation of lymphocyte activation. Nivolumab is a fully human PD-1 immune
      checkpoint inhibitor. Nivolumab inhibits the interaction between PD-1 and its
      ligands and promotes immune responses including antitumor immune response and
      antigen-specific T-cell responses to both foreign antigens as well as self
      antigens. In 2013, the Food and Drug Administration granted fast track
      designation for nivolumab in NSCLC, RCC, and melanoma. Conclusion: The
      encouraging literature on nivolumab lends credibility to the promise of immune
      checkpoint blockade, not just in terms of its feasibility as an oncotherapeutic
      strategy but also as a key tool of the future in the therapeutic approaches
      against advanced cancers.

PMID- 29333024
TI  - A Risk-benefit Assessment Approach to Selection of Adjuvant Chemotherapy in
      Elderly Patients with Early Breast Cancer: A Mini Review.
AB  - Decision-making regarding the use and selection of adjuvant chemotherapy for
      breast cancer in elderly patients is challenging due to the presence of age
      related comorbidities, frailty, and competing causes of mortality. One area,
      relatively neglected in most guidelines, is the effect of competing causes of
      mortality on presumed benefit of adjuvant chemotherapy for breast cancer in these
      patients. This article utilizes a clinical case to illustrate the principles of
      risk-benefit assessment of adjuvant chemotherapy in elderly patients. We suggest
      an approach that incorporates validated tools for estimating survival benefits of
      adjuvant chemotherapy, geriatric assessment, predicting toxicity, and estimating
      remaining life expectancy without cancer. Integration of all these variables
      provides a better picture of the possible benefits and harms of adjuvant
      chemotherapy in this population compared to conventional approaches that
      incorporate tumor-related variables and nonstandard measures of geriatric
      assessment.

PMID- 29333025
TI  - Primary Leiomyosarcoma of Breast Presenting with Metastasis: An Atypical
      Presentation with Dismal Prognosis.
AB  - Leiomyosarcoma is an extremely uncommon subtype of breast sarcoma, with <50 cases
      reported in the English literature till date. Patients usually present at an
      early stage and follow an indolent course. We reported an unusual case of
      leiomyosarcoma of breast in a post -menopausal female,presented with right side
      breast lump and pain right side hip. Histomorphological evaluation and
      immunohistochemistry confirmed the diagnosis. The patient received palliative
      radiotherapy 20 Gy in 5 fractions to right iliac bone and was started on
      chemotherapy comprising of docetaxel and epirubicin. Leiomyosarcoma of breast is
      known to have local recurrence and hematogenous metastasis, usually 10-15 years
      after the primary diagnosis. Aggressive behavior of leiomyosarcomas in the form
      of such a rapidly growing, fungating mass of 15 cm in greatest dimension with
      hematogenous metastasis at the time of initial presentation, as seen in our case,
      is extremely unusual.

PMID- 29333027
TI  - Ewing's Sarcoma of the Calcaneum.
AB  - Ewing's sarcoma of the calcaneum is rare. Radiological features of this tumor can
      be misinterpreted as other benign bone tumors due to its rarity. The overall
      prognosis of Ewing's sarcoma of calcaneum is inferior compared to other sites of
      this tumor. Hence, these tumors should have extensive radiological evaluation and
      histological confirmation as misdiagnosis and treatment delays will have
      detrimental outcomes.

PMID- 29333026
TI  - Renal Lymphoma: Primary or First Manifestation of Aggressive Pediatric B-cell
      Lymphoma.
AB  - Renal lymphoma is an uncommon renal tumor in children. Unlike renal lymphomas
      presenting as bilateral disease and renal failure, we report a boy who presented
      with unilateral renal involvement. After initial nephrectomy, he achieved
      remission with multiagent chemotherapy but relapsed systemically within 3 months.
      He was initiated on salvage chemotherapy with autologous bone marrow transplant.
      Even though the initial manifestation was localized lymphoma eventually, it
      turned out to be a systemic disease. He succumbed to disease at 14 months from
      diagnosis.

PMID- 29333028
TI  - Primary Renal Cell Lymphoma: Case Report, Diagnosis, and Management.
AB  - The symptoms of primary renal lymphoma (PRL) may mimic a renal cell carcinoma.
      Since the diagnosis is mostly after a radical nephrectomy, we recommend a
      percutaneous biopsy or cytology from the renal mass in patients who have features
      suggestive of a lymphoma. A magnetic resonance imaging may give an image more
      specific for a lymphoma. There are no clinical trials for the treatment of PRL,
      but all previously published case reports used R-CHOP and a few patients did
      better than the median survival of 6 months.

PMID- 29333029
TI  - Flagellate Rash: An Unusual Complication of Bleomycin Therapy - A Case Report
      with Brief Review of Literature.
AB  - Chemotherapy-induced skin rashes are common toxicities encountered which require
      careful assessment and evaluation as rashes could be a manifestation of primary
      malignancy itself and a variety of drugs used in combination further complicate
      the clinical scenario. Bleomycin is an anticancer antibiotic derived from
      Streptomyces verticillus and has been commonly used in the treatment of Hodgkin's
      disease, germ cell tumors and for pleurodesis. There are various dermatological
      adverse effects of bleomycin which have been previously reported in literature
      including skin peeling, hyperkeratosis, nail bed changes, Raynaud's phenomenon,
      and palmoplantar desquamation. Bleomycin-induced skin rashes are seen
      infrequently now a day due to its declining use in clinical practice. We report
      here a 29-year-old male with Stage III germ cell tumor who developed widespread
      flagellate rash after receiving 3 cycles of bleomycin-based chemotherapy which
      responded to treatment with local steroids and omission of bleomycin from further
      chemotherapy cycles.

PMID- 29333030
TI  - Multiple Myeloma Presenting as Thyroid Plasmacytoma.
AB  - Thyroid gland and thyroid cartilage infiltration in multiple myeloma (MM) are
      rare. Here, we discuss a patient who presented with hoarseness of voice and was
      found to have a hypodense lesion in right lobe of thyroid involving thyroid and
      cricoid cartilage. Fine-needle aspiration cytology with immunohistochemistry
      revealed extramedullary plasmacytoma of thyroid. MM was ruled out initially by
      serum protein electrophoresis, immunofixation, and bone marrow biopsy. Later,
      lytic lesions were found in multiple bones on radiation planning scan and he was
      finally diagnosed as case of MM with thyroid involvement. Treatment strategies of
      MM and thyroid plasmacytoma are also discussed briefly.

PMID- 29333031
TI  - A Case of Multifocal Eosinophilic Granuloma Involving Spine and Pelvis in a Young
      Adult: A Radiopathological Correlation.
AB  - We present a case of multiple osteolytic lesions in a 28-year-old adult who
      presented with headache, back pain, and hip pain of 6 months. There was no
      history of localized swelling or rise of temperature, no history of weight loss
      or evening rise of temperature. On examination, there were no focal neurological
      deficits. Routine laboratory investigations, including total leukocyte counts,
      differential leukocyte counts, hemoglobin, and platelet counts, were within
      normal limits. There was a borderline elevation of erythrocyte sedimentation
      rate. Non enhanced computer tomography (NECT) demonstrated no abnormality in the
      brain or skull bones. However, incidentally, a lytic lesion involving the third
      cervical (C3) vertebral body and the neural arch was detected which also
      demonstrated a soft tissue component adjacent to the lytic lesion. These findings
      warranted further work up; and magnetic resonance imaging of whole spine and
      pelvis was performed that revealed multiple bony lesions involving the cervical
      vertebrae, head and neck, bilateral femur, sacrum, and iliac bones. Computed
      tomography-guided biopsy was performed from the C3 vertebral lytic lesion which
      showed features of eosinophilic granuloma on histopathological evaluation.

PMID- 29333032
TI  - Macrodystrophia Lipomatosa: Clinico-patho-radiological Correlation.
AB  - Macrodystrophia lipomatosa is a rare congenital nonhereditary developmental
      anomaly. It is characterized by hamartomatous proliferation of the soft tissue
      leading to disproportionate enlargement of the limbs and digits. Since it leads
      to diagnostic dilemma, it has to be differentiated from various other conditions
      as they differ in course, prognosis, complications, and treatment. Herein, we
      present two cases with localized gigantism and discuss the various differential
      diagnoses and need for clinico-patho-radilogical correlation for diagnosis of
      this rare entity.

PMID- 29333033
TI  - Gastric Teratoma: An Unusual Presentation and Location.
AB  - The gastric teratoma is a rare tumor that usually presents as an abdominal mass,
      with or without features of gastric outlet obstruction. We report two cases of
      gastric teratoma; one - mature in a male neonate and another - ruptured immature
      gastric teratoma in a female neonate.

PMID- 29333034
TI  - Antinociceptive and Anti-inflammatory Effects of Triterpenes from Pluchea quitoc
      DC. Aerial Parts.
AB  - Background: Pluchea quitoc DC. (Asteraceae), a medicinal plant known as
      "quitoco," "caculucage," "tabacarana" and "madre-cravo," is indicated for
      inflammatory conditions such as bronchitis, arthritis, and inflammation in the
      uterus and digestive system. Objective: This study evaluated the analgesic and
      anti-inflammatory activities of the triterpenes compounds obtained from P. quitoc
      aerial parts. Materials and Methods: The triterpenes compounds beta-amyrin,
      taraxasterol and pseudo-taraxasterol in a mixture (T); beta-amyrin, taraxasterol
      and pseudo-taraxasterol acetates in a mixture (Ta); beta-amyrin, taraxasterol,
      pseudo-taraxasterol acetates in a mixture with beta-amyrin, taraxasterol and
      pseudo-taraxasterol myristates (Tafe) were analyzed in the models of nociception
      and inflammation. The evaluation of antinociceptive activity was carried out by
      the acetic acid-induced writhing and tail-flick tests while leukocyte migration
      to the peritoneal cavity was used for anti-inflammatory profile. Results: The
      oral administration of T or Tafe (40 mg/kg and 70 mg/kg) and Ta (70 mg/kg) to
      mice reduced acetic acid-induced writhing. The tail-flick response of mice was
      not affected by T or Tafe (40 mg/kg). T or Tafe (40 mg/kg) and Ta (70 mg/kg) also
      inhibited peritoneal leukocyte infiltration following the injection of
      carrageenan. Conclusion: The results demonstrate the anti-inflammatory and
      peripheral antinociceptive activity of the triterpenes beta-amyrin, taraxasterol,
      and pseudo-taraxasterol that were decreased when these were acetylated; while the
      acetylated triterpenes in mixture with myristyloxy triterpenes improved this
      activity. These compounds seem, at least in part, to be related to the plant's
      reported activity. SUMMARY: The mixtures of hydroxylated, acetylated, and
      myristate triterpenes isolated from hexanic extracts of Pluchea quitoc DC. were
      analyzed in the models of nociception and inflammation in mice. The results
      demonstrate the anti-inflammatory and peripheral antinociceptive activity of the
      triterpenes beta-amyrin, taraxasterol, and pseudo-taraxasterol. This study showed
      too that the activity of triterpenes may be decreased by their being acetylated,
      while the acetylated triterpenes in mixture with myristate triterpenes improved
      this activity.Abbreviations Used: T: Triterpenes compounds beta-amyrin,
      taraxasterol, and pseudo-taraxasterol in a mixture, Ta: Triterpenes compounds
      beta-amyrin, taraxasterol and pseudo-taraxasterol acetates in a mixture, Tafe:
      Triterpenes compounds beta-amyrin, taraxasterol, pseudo-taraxasterol acetates in
      a mixture with beta-amyrin, taraxasterol and pseudo-taraxasterol myristates,
      Ctrl: Control, Indo: Indomethacin, Dexa: Dexamethasone, EtOAc: Ethyl acetate,
      MeOH: Methanol.

PMID- 29333035
TI  - The Activity of Immunoglobulin Y Anti-Mycobacterium tuberculosis on Proliferation
      and Cytokine Expression of Rat Peripheral Blood Mononuclear Cells.
AB  - Objective: It has long been known that chickens, like mammals, are capable of
      producing antigen-specific immunoglobulin Y (IgY), which functions similar to
      IgG. The present study was performed to investigate the activity of IgY anti
      Mycobacterium tuberculosis on proliferation, interleukin (IL)-2, and interferon
      (IFN)-gamma expression of rat peripheral blood mononuclear cells (PBMCs).
      Materials and Methods: The activity of IgY anti-M. tuberculosis in different
      doses (25, 50, and 100 MUg/ml) on rat PBMCs proliferation was determined by 3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. The production
      of IL-2 and IFN-gamma in the PBMC supernatant was determined using enzyme-linked
      immunosorbent assay. Investigation was performed on mRNA expression of IL-2 and
      IFN-gamma by reverse transcription-polymerase chain reaction (RT-PCR). Results:
      IgY anti-M. tuberculosis significantly increased the proliferation of rat PBMC.
      Furthermore, IgY anti-M. tuberculosis dose dependently increased IL-2 and IFN
      gamma production in PBMC, suggesting that pharmacological activities of IgY anti
      M. tuberculosis in PBMC may be mediated by regulating the production of
      cytokines. In the RT-PCR, expression of cytokines such as IL-2 and IFN-gamma in
      PBMC cultures was increased by IgY anti-M. tuberculosis. Conclusions: We
      concluded that increasing IL-2 and IFN-gamma productions in PBMC was related to
      IgY anti-M. tuberculosis, stimulating the mRNA transcription (gene expression) of
      these cytokines which can induce proliferation of PBMC. SUMMARY: Lohman laying
      hens immunized intramuscularly with antigens of M. tuberculosis can produce
      specific IgY anti-Mycobacterium tuberculosis complexIgY anti-M. tuberculosis
      significantly increased the proliferation of rat peripheral blood mononuclear
      cell (PBMC)IgY anti-M. tuberculosis dose dependently increased interleukin 2 (IL
      2) and interferon (IFN)-gamma production in PBMCIn the reverse transcription
      polymerase chain reaction, expression of cytokines such as IL-2 and IFN-gamma in
      PBMC cultures was increased by IgY anti-M. tuberculosisThe increasing IL-2 and
      IFN-gamma productions in PBMC were related to stimulation on mRNA transcription
      which can induce proliferation of PBMC. Abbreviations Used: IgY anti-M.
      tuberculosis: Immunoglobulin Y anti-Mycobacterium tuberculosis; IL-2: Interleukin
      2; IFN-gamma: Interferon-gamma; PBMCs: Peripheral blood mononuclear cells.

PMID- 29333036
TI  - Autonomic Receptors and Nitric-Oxide Involvements in Mediating Vasorelaxation
      Effect Induced by Syzygium polyanthum Leaves Extract.
AB  - Context: Syzygium polyanthum (Wight) Walp leaves are traditionally used by Malays
      for treating hypertension. Our previous study showed that aqueous extract of S.
      polyanthum (AESP) and methanolic extract of S. polyanthum (MESP) extracts of S.
      polyanthum leaves significantly reduced blood pressure of normotensive Wistar
      Kyoto (WKY) and spontaneously hypertensive rats (SHR). Aims: This study aimed to
      investigate their vasorelaxation potential and the possible involvement of
      autonomic receptors and nitric oxide in mediating their effect. Settings and
      Design: Both extracts will be tested on isolated thoracic aorta rings of WKY and
      SHR. The involvement of autonomic receptors and nitric oxide will be elucidated
      using respective blockers. Materials and Methods: Isolated thoracic aorta rings
      from WKY and SHR were mounted onto myograph chambers to measure changes in the
      aorta tension. Increasing concentrations of AESP and MESP, from 1 MUg/ml to 10
      mg/ml were added onto the myograph chambers. Blockers such as atropine (1 MUM),
      phentolamine (1 MUM), propranolol (1 MUM), and Nomega-nitro-l-arginine methyl
      ester (100 MUM) were preincubated before addition of extracts to check for
      involvement of muscarinic, alpha- and beta-adrenergic receptors (AR) as well as
      nitric oxide, respectively. Statistical Analysis Used: Two-way ANOVA, followed by
      post hoc Bonferroni test was used, where P < 0.05 (two-tailed) was considered
      statistically significant. Results: AESP and MESP caused significant
      vasorelaxations through nitric oxide pathway. The former was mediated through
      alpha-AR while the latter was mediated by beta-adrenergic and muscarinic
      receptors. Conclusion: Vasorelaxation effect by AESP and MESP involved nitric
      oxide pathway which is possibly mediated by the autonomic receptors. SUMMARY:
      This is the first study that reveals significant vasorelaxation effect induced by
      Syzygium polyanthum leaves extract. Vasorelaxation maybe one of the possible
      mechanisms for its ability to reduce blood pressure. This study also suggested
      that the vasorelaxation effect by this plant extract may involve nitric oxide
      pathway mediated by the autonomic receptors. Abbreviations Used: AESP: Aqueous
      extract of Syzygium polyanthum leaves. MESP: Methanolic extract of Syzygium
      polyanthum leaves. SHR: spontaneously hypertensive rat, WKY: Wistar-Kyoto rat.

PMID- 29333037
TI  - Curcumin and Natural Derivatives Inhibit Ebola Viral Proteins: An In silico
      Approach.
AB  - Background: Ebola viral disease is a severe and mostly fatal disease in humans
      caused by Ebola virus. This virus belongs to family Filoviridae and is a single
      stranded negative-sense virus. There is no single treatment for this disease
      which puts forth the need to identify new therapy to control and treat this fatal
      condition. Curcumin, one of the bioactives of turmeric, has proven antiviral
      property. Objective: The current study evaluates the inhibitory activity of
      curcumin, bisdemethoxycurcumin, demethoxycurcumin, and tetrahydrocurcumin against
      Zaire Ebola viral proteins (VPs). Materials and Methods: Molecular simulation of
      the Ebola VPs followed by docking studies with ligands comprising curcumin and
      related compounds was performed. Results: The highest binding activity for VP40
      is -6.3 kcal/mol, VP35 is -8.3 kcal/mol, VP30 is -8.0 kcal/mol, VP24 is -7.7
      kcal/mol, glycoprotein is -7.1 kcal/mol, and nucleoprotein is 6.8 kcal/mol.
      Conclusion: Bisdemethoxycurcumin shows better binding affinity than curcumin for
      most VPs. Metabolite tetrahydrocurcumin also shows binding affinity comparable to
      curcumin. These results indicate that curcumin, curcuminoids, and metabolite
      tetrahydrocurcumin can be potential lead compounds for developing a new therapy
      for Ebola viral disease. SUMMARY: Curcumin, bisdemethoxycurcumin, and
      demethoxycurcumin are active constituents of turmeric. Tetrahydrocurcumin is the
      major metabolite of curcumin formed in the body after consumption and absorption
      of curcuminoidsCurcuminoids have proven antiviral activityBisdemethoxycurcumin
      showed maximum inhibition of Ebola viral proteins (VPs) among the curcuminoids in
      the docking procedure with a docking score as high as -8.3
      kcal/molTetrahydrocurcumin showed inhibitory activity against Ebola VPs close to
      that of curcumin's inhibitory action. Abbreviations Used: EBOV: Ebola virus, GP:
      Glycoprotein, NP: Nucleoprotein, NPT: Isothermal-isobaric Ensemble, amount of
      substance (N), pressure (P) and temperature (T) conserved, NVE: Canonical
      ensemble, amount of substance (N), volume (V) and temperature (T) conserved, VP:
      Viral protein.

PMID- 29333038
TI  - Antihyperglycemic Potential of Saponin-enriched Fraction from Pithecellobium
      dulce Benth. Seed Extract.
AB  - Background: Indian traditional system of medicine uses Pithecellobium dulce for
      the treatment of diabetes mellitus. Objectives: This study aims to develop an
      extract rich in saponins derived from seeds of the plant and to evaluate its
      antihyperglycemic potential in vitro and in vivo. Materials and Methods: Defatted
      seeds were extracted with methanol and processed to afford saponin-enriched
      fraction (Pithecellobium dulce saponin-enriched fraction [PDSEF]). This fraction
      was evaluated for its potential to inhibit enzymes such as alpha-glucosidase and
      alpha-amylase, in vitro. The fraction was subjected to oral toxicity study
      followed by in vivo sucrose tolerance test. An analytical high-performance liquid
      chromatography method was developed for fingerprinting of the fraction. Results:
      The method adopted for enrichment of saponins was robust enough to enrich saponin
      content to 96.37% +/-1.21% w/w. PDSEF displayed superior inhibition of enzymes
      (alpha-glucosidase and alpha-amylase with IC50 of 5.12 +/- 0.15 MUg/ml and 17.28
      +/- 0.23 MUg/ml, respectively) compared to acarbose. It was found to be safe in
      mice up to 2000 mg/kg and significantly prevented blood glucose level in sucrose
      tolerance test by inhibiting enzymes responsible for hydrolysis of sucrose.
      Conclusion: PDSEF displayed excellent antihyperglycemic activity in vitro and in
      vivo and should be evaluated further to develop it as a promising drug for the
      management of diabetes mellitus. SUMMARY: Saponin enriched fraction from P. dulce
      seeds showed significant inhibition of key enzymes responsible for digestion of
      polysaccharides. The saponin enriched fraction was found to be safe in mice and
      prevented blood glucose level in mice in sucrose tolerance test. Abbreviations
      Used: PDSEF: Pithecellobium dulce saponin-enriched fraction, IC50: Inhibitory
      concentration 50, HPLC: High performance liquid chromatography.

PMID- 29333039
TI  - Pharmacognostic Assesment of the Endemic and Vulnerable Medicinal Climber
      Cayratia pedata (Lam.) Gagnep. var. glabra Gamble and Its Antibacterial Activity.
AB  - Objective: The objective of this study is to evaluate a meticulous
      pharmacognostic cram is to supplement constructive information with regard to its
      identification, characterization, and standardization of endemic and endangered
      medicinal climber Cayratia pedata var. glabra and also screening the
      antibacterial activity of this climber. Materials and Methods: The morphological
      characters of study plant, microscopic examination of leaf powder, anatomy of
      young stem, physicochemical analysis of plant powder, extractive values,
      phytochemical analysis, powder with different chemical reagents, fluorescence
      analysis of plant powder, and other World Health Organization (WHO) recommended
      for standardization were analyzed. The antibacterial activity of this study plant
      is also analyzed. Results: C. pedata var. glabra belongs to the family Vitaceae,
      commonly known as "Kattuppirandai" is one such endemic and endangered species in
      Thaisholai, Nilgiris South Division, Western Ghats. With the patronage of veteran
      ethnic group traditional knowledge of this region, the species C. pedata var.
      glabra was selected for the pharmacognostical examination and antibacterial
      screening. There were no pharmacognostical reports of this plant, specifically to
      determine the anatomical and other physicochemical standards required for its
      quality control. The current study deals with pharmacognostical parameters for
      the aerial parts of study plant, which mainly consists of macromorphological and
      microanatomical characters, physicochemical constants (ash values and extractive
      values), fluorescence analysis, and phytochemical screening, one of the WHO
      accepted parameter for the identification of medicinal plants. The
      pharmacognostical exploration was undertaken for this species with the purpose of
      sketch the pharmacopeial standards. The antibacterial activity of this plant
      confirms the therapeutic power. Conclusion: The information obtained from
      pharmacognostical studies will be of used for supplementary pharmacological and
      therapeutical evaluation of the species and will assist in standardization for
      quality, purity, and authentication with the help, of which adulteration and
      substitution can be prevented. The antibacterial activity of this plant confirm
      the traditional knowledge of local healers on the wound healing property of this
      species and also suggest this plant species can be used as a promising source for
      the development of new pharmaceuticals that address the therapeutic needs to cure
      infectious diseases. SUMMARY: The species C. pedata var. glabra was selected for
      present research work, since this species is listed in Red data book and has a
      wider use for different ailments among the tribal population of Thiashola due to
      its high medicinal value. Pharmacognostical profile was generated from
      macroscopical analysis, microscopical studies, powder analysis, physico-chemical
      constituent values, fluorescence analysis and preliminary phytochemical
      evaluation. The antibacterial activity of this plant confirms the therapeutic
      power. Abbreviations Used: WHO: World Health Organization; IUCN: International
      Union for the Conservation of Nature.

PMID- 29333040
TI  - Pharmacological Screening of Trachyspermum ammi for Antihyperlipidemic Activity
      in Triton X-100 Induced Hyperlipidemia Rat Model.
AB  - Background: Mortality rate is increasing due to cardiovascular problems
      throughout the world. These cardiac problems are directly associated with
      dyslipidemia. Aim: The aim of this study was to evaluate the antihyperlipidemic
      effect of aqueous extract and methanol extract of Trachyspermum ammi at 1 g/kg, 3
      g/kg, and 5 g/kg dose levels in rats. Materials and Methods: For this purpose, 45
      male albino rats were used and randomly divided into nine equal groups (n = 5).
      The lipid levels were increased after 24 h of single intraperitoneal injection of
      Triton X-100 (100 mg/kg) in rats. Aqueous and methanol extracts equivalent to 1
      g/kg, 3 g/kg, and 5 g/kg were administered orally to the rats for 21 days.
      Atorvastatin (10 mg/kg) was used as standard drug. Blood samples were collected
      at 0, 2nd, 9th, 16th, and 23rd day by a direct cardiac puncture in Vacuette(r)
      heparin tubes. Serum was separated and then analyzed for lipid profile, liver
      function test (LFT), and renal function test (RFT) using standard diagnostic
      kits. Results: Results showed that extracts at 3 g/kg and 5 g/kg decreased the
      levels of total cholesterol, triglyceride, and low-density lipoprotein and
      increased high-density lipoprotein concentration in serum. T. ammi also decreased
      LFT and RFT parameters at the end of the study. Conclusion: T. ammi possessed
      antioxidant and antihyperlipidemic activities along with hepato- and nephro
      protective effects. SUMMARY: Aqueous and methanol extracts of T. ammi were
      administered orally at 1-, 3-, and 5 g/kg doses to hyperlipidemic rats (Triton X
      100 induced hyperlipidemia) and atorvastatin (10 mg/kg, orally) was used as
      standard drug. Methanol extract at 5 g/kg showed antihyperlipidemic effect that
      is identical to that of standard drug.Abbreviations Used: LDL: Low-density
      lipoprotein; TC: Total cholesterol; VLDL: Very low-density lipoprotein; HDL: High
      density lipoprotein; T. ammi: Trachyspermum ammi; WHO: World Health Organization;
      CAD: Coronary artery disease; BHT: Butylated hydroxytoluene; BUN: Blood urea
      nitrogen; AST: Aspartate transaminase; ALT: Alanine transaminase; IP:
      Intraperitoneal.

PMID- 29333041
TI  - Pharmacological Evaluation of Hepatoprotective Activity of AHPL/AYTAB/0613 Tablet
      in Carbon Tetrachloride-, Ethanol-, and Paracetamol-Induced Hepatotoxicity Models
      in Wistar Albino Rats.
AB  - Background: Hepatotoxicity ultimately leads to liver failure. Conventional
      treatment options for hepatotoxicity are limited and not safe. Objective:
      Formulation AHPL/AYTAB/0613 is developed to provide safer and effective
      hepatoprotective drug of natural origin. A study was conducted to evaluate
      hepatoprotective activity of AHPL/AYTAB/0613 (three dosages) in comparison with
      marketed formulations in carbon tetrachloride (CCl4), ethanol, and paracetamol
      induced hepatotoxicity in Wistar albino rats. Materials and Methods: Three
      separate studies were conducted in models of CCl4, ethanol, and paracetamol
      induced hepatotoxicity. Seven groups of animals were studied comparatively to
      evaluate the efficacy of AHPL/AYTAB/0613 in low, medium, and high dosage in
      comparison with silymarin and a marketed polyherbal formulation. The drugs were
      orally administered to rats for 10 days in CCl4 model and for 14 days in ethanol
      and paracetamol models. Animals were weighed periodically. After the study
      period, blood was tested for serum glutamic-oxaloacetic transaminase (SGOT),
      serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase (ALP), total
      bilirubin, and total protein levels. Liver tissue of sacrificed animals was
      examined histopathologically. Results: All the test formulations including all
      three dosages of AHPL/AYTAB/0613, significantly reduced levels of SGOT, SGPT,
      ALP, total bilirubin, in CCl4, ethanol, and paracetamol-induced hepatotoxicity
      models. There was significant increase in total protein level in all the tested
      formulations. All the test formulations effectively preserved the structural
      integrity of the hepatocellular membrane and liver cell architecture damaged by
      CCl4, ethanol, and paracetamol. When compared between groups, no statistically
      significant difference was observed. It can be concluded that AHPL/AYTAB/0613
      possesses hepatoprotective activity in CCl4, ethanol, and paracetamol-induced
      hepatotoxicity in rats. Conclusion: AHPL/AYTAB/0613 can be effectively used as a
      hepatoprotective agent in the management of hepatitis caused due to various
      toxins. SUMMARY: A polyherbal formulation AHPL/AYTAB/0613 containing Bhringaraja 
      Eclipta alba extract, Guduchi - Tinospora cordifolia extract, Daruharidra -
      Berberis aristata extract, Kakamachi - Solanum nigrum extract, Punarnava -
      Boerhaavia diffusa extract, Bhumyamalaki - Phyllanthus niruri extract, Kutaki -
      Picrorhiza kurroa extract, and Kalmegha - Andrograhis paniculata extract was
      assessed for its hepatoprotective activity. This activity was tested in carbon
      tetrachloride (CCl4), ethanol, and paracetamol-induced hepatotoxicity models in
      Wistar albino rats in comparison with two marketed formulations. It was observed
      that AHPL/AYTAB/0613 significantly reduced levels of serum glutamic-oxaloacetic
      transaminase, serum glutamic pyruvic transaminase, alkaline phosphatase, total
      bilirubin and also significantly increased total protein level. All the test
      formulations effectively preserved the structural integrity of the hepatocellular
      membrane and liver cell architecture damaged by CCl4, ethanol, and paracetamol.
      When compared between groups, no statistically significant difference was
      observed. Therefore, it was concluded that AHPL/AYTAB/0613 possesses
      hepatoprotective activity in CCl4, ethanol, and paracetamol-induced
      hepatotoxicity in rats.Abbreviations Used: CCl4: Carbon tetrachloride, SGOT:
      Serum glutamic-oxaloacetic transaminase, SGPT: Serum glutamic pyruvi
      transaminase, ALP: Alkaline phosphatase, UDCA: Ursodeoxycholic acid, US: United
      States, FDA: Food and Drug Administration, PBC: Primary biliary cirrhosis, GSTA1:
      Glutathione S-transferase A1, GSH: Glutathione, GPx: Glutathione peroxidase, GST:
      Glutathione S-transferases.

PMID- 29333042
TI  - Gas Chromatography Mass Spectrometry Profiling in Methanolic and Ethyl-acetate
      Root and Stem Extract of Corbichonia decumbens (Forssk.) Exell from Thar Desert
      of Rajasthan, India.
AB  - Background: Corbichonia decumbens (Forssk.) Exell (Molluginaceae), recently has
      moved to Lophiocarpaceae as per angiospermic plant group (APG) III system, is an
      annual or short-lived, dwarf, glabrous subshrub, prefers to grow on rocky places
      and on sand-stones in dry, hot areas of Rajasthan. This is the potential plant
      with medicinal properties. Vegetative organs under study show antioxidant, anti
      inflammatory, antiulcer, antimicrobial, and antinociception activity. Objective:
      This study was carried out to identify the phytoconstituents present in the
      methanolic and ethyl-acetate extract of root and stem of C. decumbens by GC-MS
      analysis. Materials and Methods: Powdered test samples were sequentially
      extracted with methanol and ethyl-acetate. The compounds obtained as a result of
      GC-MS screening were identified on the basis of their retention time, peak area
      and compared with that of literature available and by interpretation of mass
      spectra. Results: GC-MS analysis of a methanolic extract of root detected mome
      inositol (49.53%), guanosine (20.91%), and cis-vaccenic acid (9.25%). While ethyl
      acetate extract of root analyzed pentadecanoic acid (17.91%), octadecanoic acid
      (15.01%) and cis-vaccenic acid (12.04%). Methanolic extract of stem detected mome
      inositol (75.47%), pentadecanoic acid (6.04%), and 7-tetradecenal, (Z) (4.54%)
      while ethyl-acetate extract of stem revealed the presence of 1-heptacosanol
      (17.35%), hexadecanoic acid (17.17%), and octadecanal (12.64%). Conclusion: The
      results suggest that C. decumbens (Forssk.) Exell is a plant of potential
      medicinal value, yielding various bioactive compounds that confirm the
      application of this plant as a plant-based drug in pharmacy-industry. SUMMARY:
      Extraction is the most important step in the analysis of bioactive compounds
      present in botanical preparations. The strength of solvent plays a key role in
      this process, methanol as well as ethyl-acetate showed better response as far as
      extraction potency is concerned. Gas chromatography mass spectrometry analysis is
      highly reliable, and the interpretations of the results are of high-quality. This
      tool is in particular useful for confirming of the presence of bioactive
      substances. The results suggest that Corbichonia decumbens (Forssk.) Exell can be
      used for drug formulations against some major disorders, i.e., cancer, ulcer,
      tuberculosis, arthritis, etc.Abbreviations Used: GC-MS: Gas Chromatography-Mass
      Spectrometry, kPa: Kilopascal, RT: Retention time, MF: Molecular formula, MW:
      Molecular weight.

PMID- 29333044
TI  - Antiplasmodial Activity of Isolated Polyphenols from Alectryon serratus Leaves
      Against 3D7 Plasmodium falciparum.
AB  - Background: Alectryon serratus was selected from a screening program devoted to
      search naturally occurring antimalarial compound from plants in Alas Purwo
      National Park, Banyuwangi, East Java, Indonesia. The previous studies showed that
      ethanol extract of A. serratus leaves contains some polyphenol compounds.
      Objective: This study was designed to isolate and investigate antiplasmodial
      activity of polyphenol compounds. Material and Methods: The ethanol extract of A.
      serratus leaves was fractioned using liquid-liquid fractionation and column
      chromatography. Isolated compounds were identified using High-performance liquid
      chromatography, ultraviolet-visible, nuclear magnetic resonance, and compared
      with references. The isolates were tested in vitro for antiplasmodial activity
      against chloroquine-sensitive 3D7 strain of Plasmodium falciparum. Thin blood
      smears were used to assess the levels of parasitemia and growth inhibition of the
      isolates. Result: Half maximal Inhibitory concentration of Gallic acid (1),
      methyl gallate (2), and kempferol-3-O-rhamnoside (3) were 0.0722 MUM, 0.0128 MUM,
      and 3.4595 MUM, respectively. Conclusion: The results suggest that gallic acid,
      methyl gallate, and kempferol-3-O-rhamnoside isolated from A. serratus leaves
      have antiplasmodial activity and are potential to be developed as antimalarial
      drugs. SUMMARY: The ethanol extract of Alectryon serratus leaves was successively
      fractionated in CH2Cl2, EtOAc, and n-butanol. EtOAc fraction was fractionated
      using column chromatography and purified using preparative thin-layer
      chromatography (TLC). Isolates were studied for their antiplasmodial activity on
      parasites culture of chloroquine-sensitive 3D7 strain of Plasmodium falciparum.
      Parasitemia percentages, growth percentages, and inhibition percentages of each
      group were calculated. The half maximal inhibitory concentration (IC50) values
      that represent the concentration required to inhibit 50% of Plasmodium growth
      were calculated from a calibration curve using linear regression. The results
      suggest that isolates have antiplasmodial activity and are responsible in the
      antimalarial activity of Alectryon serratus leaves. Abbreviations Used: S.F:
      Subfraction, EGCG: Epigallocatechingallate, EGC: Epigallocatechin.

PMID- 29333043
TI  - Picroside I and Picroside II from Tissue Cultures of Picrorhiza kurroa.
AB  - Background: Picrorhiza kurroa (PK) belongs to Scrophulariaceae family and is a
      representative endemic, medicinal herb, widely distributed throughout the higher
      altitudes of alpine Himalayas from west to east, between 3000 and 4500 m above
      mean sea level. Objective: The objective of the present study is to assess the
      production of picroside I and picroside II from tissue cultures of PK. Materials
      and Methods: Auxiliary shoot tips of PK were incubated in Murashige and Skoog
      medium supplemented with indole-3-butyric acid and kinetin phytohormones. The
      callus produced was collected at different time intervals and was processed for
      extraction of picroside I and picroside II followed by thin layer chromatography
      and high-performance liquid chromatography HPLC analysis. Results: The maximum
      growth index was found to be 5.109 +/- 0.159 at 16-week-old callus culture. The
      estimation of picroside-I and picroside-II was carried out by (HPLC) analysis;
      quantity of secondary metabolite found to be 16.37 +/- 0.0007 mg/g for PK-I and
      6.34 +/- 0.0012 mg/g for PK-II. Conclusion: This is the first attempt to produce
      the Picroside-I and II in large amount by the tissue culture technique. It can be
      observed that the method of callus culture can be used in production of secondary
      metabolites Picroside-I and II from PK. SUMMARY: Picrorhiza kurroa is a high
      value medicinal herb due to rich source of hepatoprotective metabolites,
      Picroside-I and Picroside-II. The medicinal importance of P. kurroa is due to its
      pharmacological properties like hepatoprotective, antioxidant (particularly in
      liver), antiallergic and antiasthamatic, anticancer activity particularly in
      liver and immunomodulatory. Shoot apices which were produced a good response was
      inoculated on selected medium i.e., on MS medium containing 2, 4 D (mg/l) + KN
      (1mg/l) for induction of callus. The initiation of callus was observed after
      4weeks and it was light green and fragile Maximum growth was observed with 3% w/v
      of sucrose supplement. The callus culture was maintained and growth index was
      recorded after every subculture. The growth index was calculated from the
      obtained final dried weight divided by initial weight.Abbreviations Used: PK
      Picrorhizakurroa, IBA-Indole-3-butyricacid, KN-Kinetin, 2,4D-2,4Dichlorophenoxy
      acetic acid.

PMID- 29333045
TI  - In vitro Antiproliferative Effect of Earthworm Coelomic Fluid of Eudrilus
      Eugeniae, Eisenia Foetida, and Perionyx Excavatus on Squamous Cell Carcinoma-9
      Cell Line: A Pilot Study.
AB  - Introduction: The earthworm coelomic fluid (ECF) has shown proven
      antiproliferative effect against breast, liver, gastrointestinal, and brain
      cancer, but it is least explored in oral cancer. The present in vitro study is an
      attempt to investigate the antiproliferative activity of ECF on oral cancer cell
      line squamous cell carcinoma (SCC)-9. Materials and Methods: ECF was collected
      from the species Eudrilus eugeniae (EE), Eisenia foetida (EF), and Perionyx
      excavatus (PE) stored at -80 degrees C. Percentage inhibition of ECF on squamous
      cell carcinoma-9 cells in vitro was recorded at 24 h. Protein estimation was done
      using Bradford protein assay validated by the biuret method. Cytotoxicity was
      tested at 2.5, 5, 10, 20, 40, and 80 MUg/ml concentrations by 3-(4,5
      dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay in SCC-9 cells in
      vitro. GraphPad Prism 7.0 software was used to calculate the inhibitory
      concentration (IC50). Chi-square test was used to analyze the difference between
      samples. Results: The test samples EE, EF, and PE inhibited the growth of SCC-9
      cells significantly in a dose-dependent manner, and the IC50 values were found to
      be 4.6, 44.69, and 5.27 MUg/ml, respectively. The antiproliferative effect was
      found to be variable among the three earthworm species with EE showing the most
      promising effect followed by PE and EF. Conclusion: Establishing the
      antiproliferative effect of ECF on oral cancer cells could be an initial step
      toward drug development and future anticancer research. The preliminary
      investigation has shown that ECF has a promising antiproliferative effect on oral
      cancer cells in vitro. SUMMARY: The present pilot study evaluated the in vitro
      antiproliferative effect of earthworm coelomic fluid (ECF) of Eudrilus eugeniae
      (EE), Eisenia foetida (EF), and Perionyx excavatus (PE) on squamous cell
      carcinoma-9 cell line. The ECF inhibitory activity was promising at inhibitory
      concentration values of 4.6, 44.69, and 5.27 MUg/ml, respectively. Further
      studies pertaining to antiproliferative mechanism of EE, EF, and PE have been
      planned.Abbreviations Used: ECF: Earthworm coelomic fluid, EE: Eudrilus eugeniae,
      EF: Eisenia foetida, PE: Perionyx excavatus, MTT: 3-(4,5-dimethylthiazol-2-yl)
      2,5-diphenyltetrazolium bromide, SCC: Squamous cell carcinoma, BSA: Bovine serum
      albumin, PBS: Phosphored buffered saline, ATCC: American Type Culture Collection.

PMID- 29333046
TI  - Development and validation of High-performance Thin-layer Chromatography Method
      for Simultaneous Determination of Polyphenolic Compounds in Medicinal Plants.
AB  - Context: Quantitative standardization of plant-based products is challenging
      albeit essential to maintain their quality. Aims: This study aims to develop and
      validate high-performance thin-layer chromatography (HPTLC) method for the
      simultaneous determination of rutin (Ru), quercetin (Qu), and gallic acid (Ga)
      from Psidium guajava Linn. (PG) and Aegle marmelos (L.) Correa. (AM) and
      correlate with antioxidant activity. Materials and Methods: The stock solution (1
      mg/mL) of standard Ru, Qu, and Ga in methanol: Water (1:1) was serially diluted
      and spotted (5 MUL) on slica gel 60 F254 thin-layer chromatography plates.
      Toluene: Ethyl acetate: Formic acid: Methanol (3:4:0.8:0.7, v/v/v) was selected
      as mobile phase for analysis at 254 nm. Hydroalcoholic (1:1) extracts of leaves
      of PG and AM were fractionated and similarly analyzed. Antioxidant activity was
      also determined using 2, 2-diphenyl-1-picrylhydrazyl assay. Results: The
      developed method was robust and resolved Ru, Qu, and Ga at Rf 0.08 +/- 0.02, 0.76
      +/- 0.01, and 0.63 +/- 0.02, respectively. The intra-day, interday precision, and
      interanalyst were <2% relative standard deviation. The limit of detection and
      limit of quantification for Ru, Qu, and Ga were 4.51, 4.2, 5.27, and 13.67,
      12.73, 15.98 ng/spot, respectively. Antioxidant activity (Log 50% inhibition) of
      PG and AM was 4.947 +/- 0.322 and 6.498 +/- 0.295, respectively. Conclusion: The
      developed HPTLC method was rapid, accurate, precise, reproducible, and specific
      for the simultaneous estimation of Ru, Qu, and Ga. SUMMARY: HPTLC method for
      simultaneous determination and quantification of Rutin, Quercetin and Gallic
      acid, is reported for quality control of herbal drugs.Abbreviations Used: A:
      Aqueous fraction; AM: Aegle marmelos L. Correa; B: Butanol fraction; C:
      Chloroform fraction; EA: Ethyl acetate fraction; Ga: Gallic acid; H: Hexane
      fraction; HA: Hydroalcoholic extract; HPTLC: High-performance thin-layer
      chromatography; PG: Psidium guajava; Qu: Quercetin; Ru: Rutin.

PMID- 29333047
TI  - Assessment of Nutritional Quality and Global Antioxidant Response of Banana (Musa
      sp. CV. Nanjangud Rasa Bale) Pseudostem and Flower.
AB  - Background: The assessment of the nutritional composition and phytochemical
      screening of banana pseudostem (PB) and flower (FB) advocate this nonconventional
      food source for routine consumption, considering its various health benefits.
      Objectives: The aim is to assess the proximate nutrient composition, fatty acids,
      minerals, amino acid profile, and global antioxidant response (GAR) of PB and FB.
      Methods: Standard analytical procedures were used to determine the nutritional
      quality and GAR of PB and FB. Results: The chemical analysis illustrated that
      functional profile (water holding capacity, oil holding capacity, swelling power,
      and solubility), and proximate (ash, moisture, protein, fat, dietary fiber, and
      carbohydrate) contents were substantially high in FB than PB. With a well
      proportionate amino acid profile, PB (0.56) and FB (0.54) comprised of a high
      ratio of essential to nonessential amino acids than those of FAO/WHO requirement
      (0.38). The mineral analysis revealed that PB and FB were rich in macro and micro
      minerals in the order K > Ca > Mg > P > Na and K > Mg > Na > Ca > P,
      respectively. Linoleic acid was found to be the major component in PB and FB.
      Besides, total antioxidant activity conducted for PB and FB by GAR method,
      measuring both bio-accessible and insoluble fractions, revealed that the soluble
      fraction fared better than the chemical extracts. Conclusion: The results
      revealed high nutritional qualities of the byproducts of banana and the low cost
      of its production promotes their use as a prospective nonconventional food
      resource with high nutraceutical value. SUMMARY: AOAC: Association of Analytical
      CommunitiesFAO/WHO: Food and Agriculture Organization of the United Nations/World
      health organization Abbreviations Used: Banana flower was more potent than banana
      pseudostem in terms of its nutritional quality and total antioxidant capacity
      affirming their usefulness (of both the secondary products) in the pharmaceutical
      sector as a nutritional supplement due to the health-related properties of
      dietary fibre and associated bioactive compounds.

PMID- 29333048
TI  - Astaxanthin Ameliorates Hepatic Damage and Oxidative Stress in Carbon
      Tetrachloride-administered Rats.
AB  - Background: Astaxanthin is of carotenoids group which possess strong antioxidant
      properties. The present study was conducted to evaluate the hepatoprotective
      effects of astaxanthin in carbon tetrachloride (CCl4)-treated rats. Materials and
      Methods: Female Long-Evans rats were administered with CCl4 orally (1 ml/kg)
      twice a week for 2 weeks and were treated with astaxanthin (10 mg/kg) every day
      for 2 weeks. Blood plasma samples were isolated from each group and were analyzed
      for alanine aminotransferase (ALT), aspartate aminotransferase (AST), and
      alkaline phosphatase activities. Oxidative stress parameters such as
      malondialdehyde (MDA), nitric oxide (NO), and advanced protein oxidation product
      (APOP) were measured. Several enzyme functions such as myeloperoxidase (MPO),
      superoxide dismutase (SOD), and catalase (CAT) activities in the plasma and liver
      tissues were also analyzed. Moreover, inflammation and tissue fibrosis were also
      confirmed by histological staining of liver tissues. Results: This investigation
      revealed that CCl4 administration in rats increased plasma AST, ALT, and ALP
      activities which were normalized by astaxanthin treatment. Moreover, CCl4
      administration increased as MDA, NO, and APOP level both in plasma and tissues
      compared to control rats. Astaxanthin also exhibited a significant reduction of
      those parameters in CCl4-administered rats. Astaxanthin treatment also restored
      the CAT and SOD activities and lowered MPO activity in CCl4-administered rats.
      Histological assessment also revealed that the astaxanthin prevented the
      inflammatory cells infiltration, decreased free iron deposition, and fibrosis in
      liver of CCl4-administered rats. Conclusion: These results suggest that
      astaxanthin protects liver damage induced by CCl4 by inhibiting lipid
      peroxidation and stimulating the cellular antioxidant system. SUMMARY: Carbon
      tetrachloride (CCl4) administration increased oxidative stress-mediated hepatic
      damage and inflammation in ratsAstaxanthin, a potent antioxidant, prevents
      oxidative stress and inflammatory cells infiltration in CCl4-administered
      ratsAstaxanthin also ameliorated the progression of hepatic fibrosis in CCl4
      administered rats. Abbreviations Used: APOP: Advanced protein oxidation product;
      AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; ALP: Alkaline
      phosphatase; CAT: Catalase; CCl4: Carbon tetrachloride; CVD: Cardiovascular
      disease; HSCs: Hepatic stellate cells; H2O2: Hydrogen peroxide; MDA:
      Malondialdehyde; MMP2: Matrix metalloproteinase2; MPO: Myeloperoxidase; NF
      kappaB: Nuclear factor kappa B; NO: Nitric oxide; Nrf2: Nuclear factor erythroid
      2-related factor 2; .ONOO-: Peroxynitrate; ROS: Reactive oxygen species; SOD:
      superoxide dismutase; TCA: Trichloroacetic acid; TBA: Thiobarbituric acid; TGF-1:
      Transforming growth factor 1, TGF-beta: Transforming growth factor-beta; TIMP1:
      Tissue inhibitor of metalloproteinase 1; TNF-alpha: Tumor necrosis factor
      alpha;.CCl3: Trichloromethyl free radical; CCl3O2-: Trichloroperoxyl radical.

PMID- 29333050
TI  - Improvement of Insulin Secretion and Pancreatic beta-cell Function in
      Streptozotocin-induced Diabetic Rats Treated with Aloe vera Extract.
AB  - Background: Diabetes mellitus is a metabolic disorder characterized by chronic
      hyperglycemia. Plant extracts and their products are being used as an alternative
      system of medicine for the treatment of diabetes. Aloe vera has been
      traditionally used to treat several diseases and it exhibits antioxidant, anti
      inflammatory, and wound-healing effects. Streptozotocin (STZ)-induced Wistar
      diabetic rats were used in this study to understand the potential protective
      effect of A. vera extract on the pancreatic islets. Objective: The aim of the
      present study was to evaluate the A. vera extract on improvement of insulin
      secretion and pancreatic beta-cell function by morphometric analysis of
      pancreatic islets in STZ-induced diabetic Wistar rats. Materials and Methods:
      After acclimatization, male Wistar rats, maintained as per the Committee for the
      Purpose of Control and Supervision of Experiments on Animals guidelines, were
      randomly divided into four groups of six rats each. Fasting plasma glucose and
      insulin levels were assessed. The effect of A. vera extract in STZ-induced
      diabetic rats on the pancreatic islets by morphometric analysis was evaluated.
      Results: Oral administration of A. vera extract (300 mg/kg) daily to diabetic
      rats for 3 weeks showed restoration of blood glucose levels to normal levels with
      a concomitant increase in insulin levels upon feeding with A. vera extract in STZ
      induced diabetic rats. Morphometric analysis of pancreatic sections revealed
      quantitative and qualitative gain in terms of number, diameter, volume, and area
      of the pancreatic islets of diabetic rats treated with A. vera extract when
      compared to the untreated diabetic rats. Conclusion: A. vera extract exerts
      antidiabetic effects by improving insulin secretion and pancreatic beta-cell
      function by restoring pancreatic islet mass in STZ-induced diabetic Wistar rats.
      SUMMARY: Fasting plasma glucose (FPG) and insulin levels were restored to normal
      levels in diabetic rats treated with Aloe vera extractIslets of pancreas were
      qualitatively and quantitatively restored to normalcy leading to restoration of
      FPG and insulin levels of diabetic rats treated with Aloe vera
      extractMorphometric analysis of pancreatic sections revealed quantitative and
      qualitative gain in terms of number, diameter, volume, and area of the pancreatic
      islets of diabetic rats treated with Aloe vera extract when compared to the
      untreated diabetic rats. Abbreviations Used:A. vera, FPG: Fasting plasma glucose,
      STZ: Streptozotocin, BW: Body weight.

PMID- 29333049
TI  - Marine-derived Fungi Extracts Enhance the Cytotoxic Activity of Doxorubicin in
      Nonsmall Cell Lung Cancer Cells A459.
AB  - Background: Drug resistance is a major concern in the current chemotherapeutic
      approaches and the combination with natural compounds may enhance the cytotoxic
      effects of the anticancer drugs. Therefore, this study evaluated the cytotoxicity
      of crude ethyl extracts of six marine-derived fungi - Neosartorya tsunodae KUFC
      9213 (E1), Neosartorya laciniosa KUFC 7896 (E2), Neosartorya fischeri KUFC 6344
      (E3), Aspergillus similanensis KUFA 0013 (E4), Neosartorya paulistensis KUFC 7894
      (E5), and Talaromyces trachyspermum KUFC 0021 (E6) - when combined with
      doxorubicin (Dox), in seven human cancer cell lines. Materials and Methods: The
      antiproliferative activity was primarily assessed by the 3-(4,5-dimethylthiazol-2
      yl)-2,5-diphenyltetrazolium bromide assay. Results: Two extracts, E1 and E2,
      demonstrated a significant enhancement of Dox's cytotoxicity in nonsmall cell
      lung cancer A549 cells. Accumulation of Dox in the nuclei increased when A549
      cells were treated in combination with extracts E1 and E2, with induction of cell
      death observed by the nuclear condensation assay. The combination of E2 with Dox
      increased the DNA damage as detected by the comet assay. Ultrastructural
      observations by transmission electron microscopy suggest an autophagic cell death
      due to an increase of autophagic vesicles, namely with the combination of Dox
      with E1 and E2. Conclusion: These findings led to the conclusion that the fungal
      extracts E1 and E2 potentiate the anticancer action of Dox, through nuclear
      accumulation of Dox with induction of cell death mainly by cytotoxic autophagy.
      SUMMARY: Fungal extracts increase the cytotoxic activity of doxorubicin (Dox) in
      lung cancer cellsNuclear accumulation of Dox, DNA damage, and cell death as a
      mechanism of actionFungal extracts may potentiate the anticancer activity of
      conventional drugs.Abbreviations Used: A375: Human malignant melanoma cell line,
      A549: Human non small lung cancer cell line, DAPI: 4,6-Diamidino-2-phenylindole,
      DMEM: Dulbecco's Modified Eagle Medium, DMSO: Dimethylsulfoxide, Dox:
      Doxorubicin, DSBs: DNA double-strand breaks, E1: Neosartorya tsunodae KUFC 9213,
      E2: Neosartorya laciniosa KUFC 7896, E3: Neosartorya fischeri KUFC 6344, E4:
      Aspergillus similanensis KUFA 0013, E5: Neosartorya paulistensis KUFC 7894, E6:
      Talaromyces trachyspermum KUFC 0021, FBS: Fetal bovine serum, HCT116: Human
      colorectal carcinoma cell line, HEPES: (N-[2-hydroxyethyl] piperazine-N'- [2
      ethane-sulfonic acid]), HepG2: Human hepatocellular carcinoma cell line, HT29:
      Human Caucasian colon adenocarcinoma Grade II cell line, IC50: Concentration of
      the extract or Dox that inhibits cell viability by 50%, LRP: Lung resistance
      related protein, MCF7: Human breast adenocarcinoma cell line, MEM: Minimum
      Essential Medium Eagle, MRPs: Multidrug resistance-associated proteins, MTT: 3
      (4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, PBS: Phosphate
      buffered saline, NSCLC: Nonsmall cell lung cancer, P-gp: P-glycoprotein, ROS:
      Reactive oxygen species, RPMI: Roswell Park Memorial Institute Medium, TEM:
      Transmission electron microscopy, U251: Human glioblastoma astrocytoma cell line.

PMID- 29333051
TI  - Therapeutic Significance of Loligo vulgaris (Lamarck, 1798) ink Extract: A
      Biomedical Approach.
AB  - Background: The squid ink extract is well known for its biomedical properties.
      Objective: In this study, squid Loligo vulgaris was collected from Tuticorin
      costal water, Bay of Bengal, India. Materials and Methods: Proximate composition
      of the crude squid ink was studied and found to have protein as the major
      component over lipid and carbohydrates. Further, bioactive fractions of squid ink
      were extracted with ethanol, and therapeutic applications such as hemolytic,
      antioxidant, antimicrobial, and in vitro anti-inflammatory properties were
      analyzed using standard methods. Results: In hemolytic assay, the squid ink
      extract exhibited a maximum hemolytic activity of 128 hemolytic unit against
      tested erythrocytes. In DPPH assay, the ethanolic extract of squid ink has
      exhibited an antioxidant activity of 83.5%. The squid ink was found to be potent
      antibacterial agent against the pathogens tested. 200 MUL of L. vulgaris ink
      extract showed remarkable antibacterial activity as zone of inhibition against
      Escherichia coli (28 mm), Klebsiella pneumoniae (22 mm), Pseudomonas aeruginosa
      (21 mm), and Staphylococcus aureus (24 mm). The 68.9% inhibition of protein
      denaturation by the squid ink extract indicated that it has very good in vitro
      anti-inflammatory properties. The Fourier transform infrared spectroscopy
      analysis of the ethanolic extracts of the squid ink indicated the presence of
      functional groups such as 1 degrees  and 2 degrees  amines, amides, alkynes
      (terminal), alkenes, aldehydes, nitriles, alkanes, aliphatic amines, carboxylic
      acids, and alkyl halides, which complements the biochemical background of
      therapeutic applications. Conclusion: Hence, results of this study concluded that
      the ethanolic extract of L. vulgaris has many therapeutic applications such as
      antimicrobial, antioxidant, and anti-inflammatory activities. SUMMARY: Squid ink
      is very high in a number of important nutrients. It's particularly high in
      antioxidants for instance, which as well all know help to protect the cells and
      the heart against damage from free radicals. In the present study, the squid ink
      have antioxidant, anti-inflammatory and cytotoxic properties and can be
      considered as promising the developing the drugs. Abbreviations Used: DPPH: 2,2
      diphenyl-1-picrylhydrazyl, FTIR: Fourier-transform infrared spectroscopy, BSA:
      Bovine Serum Albumin.

PMID- 29333052
TI  - A calcium rise occurs as activating Drosophila eggs move through the female
      reproductive tract.

PMID- 29333053
TI  - An Emic, Mixed Methods Approach to Defining and Measuring Positive Parenting
      Among Low-Income, Black Families.
AB  - Research Findings: This within-group exploratory sequential mixed methods
      investigation sought to identify how ethnically diverse, urban-residing, low
      income Black families conceptualize positive parenting. During the item
      development phase 119 primary caregivers from Head Start programs participated in
      focus groups and interviews. These qualitative data were content analyzed using a
      three-stage iterative process that resulted in the development of a final set of
      72 items for a paper-and-pencil measure. In the measure validation phase of the
      study initial construct validity of the 72-item measure was assessed with an
      independent sample of 665 respondents. Common factor analyses revealed five
      dimensions of positive parenting on the Black Parenting Strengths in Context
      (BPSC) scale that related in expected ways with other parent self-report
      measures. Practice and Policy: BPSC dimensions provide initial support for a more
      nuanced operationalization of positive parenting than currently exists in any
      single scale for use with this group, and hold promise for better honoring the
      culture- and context-specific parenting goals and practices that low-income,
      Black parents subjectively view as important for producing healthy developmental
      outcomes for their children.

PMID- 29333054
TI  - On Fitting a Multivariate Two-Part Latent Growth Model.
AB  - A 2-part latent growth model can be used to analyze semicontinuous data to
      simultaneously study change in the probability that an individual engages in a
      behavior, and if engaged, change in the behavior. This article uses a Monte Carlo
      (MC) integration algorithm to study the interrelationships between the growth
      factors of 2 variables measured longitudinally where each variable can follow a 2
      part latent growth model. A SAS macro implementing Mplus is developed to estimate
      the model to take into account the sampling uncertainty of this simulation-based
      computational approach. A sample of time-use data is used to show how maximum
      likelihood estimates can be obtained using a rectangular numerical integration
      method and an MC integration method.

PMID- 29333055
TI  - Corporal Punishment in U.S. Public Schools: Prevalence, Disparities in Use, and
      Status in State and Federal Policy.
AB  - School corporal punishment is currently legal in 19 states, and over 160,000
      children in these states are subject to corporal punishment in schools each year.
      Given that the use of school corporal punishment is heavily concentrated in
      Southern states, and that the federal government has not included corporal
      punishment in its recent initiatives about improving school discipline, public
      knowledge of this issue is limited. The aim of this policy report is to fill the
      gap in knowledge about school corporal punishment by describing the prevalence
      and geographic dispersion of corporal punishment in U.S. public schools and by
      assessing the extent to which schools disproportionately apply corporal
      punishment to children who are Black, to boys, and to children with disabilities.
      This policy report is the first-ever effort to describe the prevalence of and
      disparities in the use of school corporal punishment at the school and school
      district levels. We end the report by summarizing sources of concern about school
      corporal punishment, reviewing state policies related to school corporal
      punishment, and discussing the future of school corporal punishment in state and
      federal policy.

PMID- 29333056
TI  - Individual Differences in Phonological Feedback Effects: Evidence for the
      Orthographic Recoding Hypothesis of Orthographic Learning.
AB  - Share (1995) has proposed phonological recoding (the translation of letters into
      sounds) as a self-teaching mechanism through which readers establish complete
      lexical representations. More recently, McKague et al. (2008) proposed a similar
      role for orthographic recoding, i.e., feedback from sounds to letters, in
      building and refining lexical representations. We reasoned that an interaction
      between feedback consistency measures and spelling ability in a spelling decision
      experiment would lend support to this hypothesis. In a linear mixed effects
      logistic regression of accuracy data this interaction was significant. Better
      spellers but not poorer spellers were immune to feedback effects in deciding if a
      word is spelled correctly, which is consistent with McKague et al.'s prediction
      that the impact of phonological feedback on word recognition will diminish when
      the orthographic representation for an item is fully specified. The study
      demonstrates the importance of considering individual differences when
      investigating the role of phonology in reading.

PMID- 29333057
TI  - Family counts: deciding when to murder among the Icelandic Vikings.
AB  - In small scale societies, lethal attacks on another individual usually invite
      revenge by the victim's family. We might expect those who perpetrate such attacks
      to do so only when their own support network (mainly family) is larger than that
      of the potential victim so as to minimise the risk of retaliation. Using data
      from Icelandic family sagas, we show that this prediction holds whether we
      consider biological kin or affinal kin (in-laws): on average, killers had twice
      as many relatives as their victims. These findings reinforce the importance of
      kin as a source of implicit protection even when they are not physically present.
      The results also support Hughes' (1988) claim that affines are biological kin
      because of the shared genetic interests they have in the offspring generation.

PMID- 29333058
TI  - Acquisition of a socially learned tool use sequence in chimpanzees: Implications
      for cumulative culture.
AB  - Cumulative culture underpins humanity's enormous success as a species. Claims
      that other animals are incapable of cultural ratcheting are prevalent, but are
      founded on just a handful of empirical studies. Whether cumulative culture is
      unique to humans thus remains a controversial and understudied question that has
      far-reaching implications for our understanding of the evolution of this
      phenomenon. We investigated whether one of human's two closest living primate
      relatives, chimpanzees, are capable of a degree of cultural ratcheting by
      exposing captive populations to a novel juice extraction task. We found that
      groups (N = 3) seeded with a model trained to perform a tool modification that
      built upon simpler, unmodified tool use developed the seeded tool method that
      allowed greater juice returns than achieved by groups not exposed to a trained
      model (non-seeded controls; N = 3). One non-seeded group also discovered the
      behavioral sequence, either by coupling asocial and social learning or by
      repeated invention. This behavioral sequence was found to be beyond what an
      additional control sample of chimpanzees (N = 1 group) could discover for
      themselves without a competent model and lacking experience with simpler,
      unmodified tool behaviors. Five chimpanzees tested individually with no social
      information, but with experience of simple unmodified tool use, invented part,
      but not all, of the behavioral sequence. Our findings indicate that (i) social
      learning facilitated the propagation of the model-demonstrated tool modification
      technique, (ii) experience with simple tool behaviors may facilitate individual
      discovery of more complex tool manipulations, and (iii) a subset of individuals
      were capable of learning relatively complex behaviors either by learning
      asocially and socially or by repeated invention over time. That chimpanzees learn
      increasingly complex behaviors through social and asocial learning suggests that
      humans' extraordinary ability to do so was built on such prior foundations.

PMID- 29333060
TI  - Optimising human community sizes.
AB  - We examine community longevity as a function of group size in three historical,
      small scale agricultural samples. Community sizes of 50, 150 and 500 are
      disproportionately more common than other sizes; they also have greater
      longevity. These values mirror the natural layerings in hunter-gatherer societies
      and contemporary personal networks. In addition, a religious ideology seems to
      play an important role in allowing larger communities to maintain greater
      cohesion for longer than a strictly secular ideology does. The differences in
      optimal community size may reflect the demands of different ecologies, economies
      and social contexts, but, as yet, we have no explanation as to why these numbers
      seem to function socially so much more effectively than other values.

PMID- 29333059
TI  - Innate food aversions and culturally transmitted food taboos in pregnant women in
      rural southwest India: separate systems to protect the fetus?
AB  - Pregnancy increases women's nutritional requirements, yet causes aversions to
      nutritious foods. Most societies further restrict pregnant women's diet with food
      taboos. Pregnancy food aversions are theorized to protect mothers and fetuses
      from teratogens and pathogens or increase dietary diversity in response to
      resource scarcity. Tests of these hypotheses have had mixed results, perhaps
      because many studies are in Westernized populations with reliable access to food
      and low exposure to pathogens. If pregnancy food aversions are adaptations,
      however, then they likely evolved in environments with uncertain access to food
      and high exposure to pathogens. Pregnancy food taboos, on the other hand, have
      been theorized to limit resource consumption, mark social identity, or also
      protect mothers and fetuses from dangerous foods. There have been few tests of
      evolutionary theories of culturally transmitted food taboos. We investigated
      these and other theories of psychophysiological food aversions and culturally
      transmitted food taboos among two non-Western populations of pregnant women in
      Mysore, India, that vary in food insecurity and exposure to infectious disease.
      The first was a mixed caste rural farming population (N = 72), and the second was
      the Jenu Kurubas, a resettled population of former hunter-gatherers (N = 30).
      Women rated their aversions to photos of 31 foods and completed structured
      interviews that assessed aversions and socially learned avoidances of foods,
      pathogen exposure, food insecurity, sources of culturally acquired dietary
      advice, and basic sociodemographic information. Aversions to spicy foods were
      associated with early trimester and nausea and vomiting, supporting a protective
      role against plant teratogens. Variation in exposure to pathogens did not explain
      variation in meat aversions or avoidances, however, raising some doubts about the
      importance of pathogen avoidance. Aversions to staple foods were common, but were
      not associated with resource stress, providing mixed support for the role of
      dietary diversification. Avoided foods outnumbered aversive foods, were believed
      to be abortifacients or otherwise harmful to the fetus, influenced diet
      throughout pregnancy, and were largely distinct from aversive foods. These
      results suggest that aversions target foods with cues of toxicity early in
      pregnancy, and taboos target suspected abortifacients throughout pregnancy.

PMID- 29333061
TI  - Critical appraisal of Rome IV criteria: hypersensitive esophagus does belong to
      gastroesophageal reflux disease spectrum.
AB  - The Rome IV Committee introduced a major change in the classification of
      functional gastrointestinal disorders, proposing a more restrictive definition of
      gastroesophageal reflux disease (GERD). It was suggested that hypersensitive
      esophagus (HE) may sit more firmly within the functional realm. It was suggested
      that GERD diagnosis should be based upon abnormal acid exposure time (AET) only,
      implying no advantage of impedance-pH over pH monitoring. Symptom association
      probability (SAP), symptom index (SI) and heartburn relief with proton pump
      inhibitor (PPI) therapy were regarded as unreliable, whereas a lack of response
      to PPI was considered as evidence of functional heartburn. These assumptions are
      contradicted by numerous studies showing the clinical relevance of weakly acidic
      refluxes and the diagnostic utility of SAP, SI and new impedance parameters,
      namely the post-reflux swallow-induced peristaltic wave (PSPW) index and the mean
      nocturnal baseline impedance (MNBI). The PSPW index and MNBI provide significant
      diagnostic advantage, particularly in patients with normal AET who can be
      classified as HE when both parameters are abnormal, even though SAP and SI are
      negative. Visceral pain modulators are recommended by the Rome IV Committee
      despite scanty evidence of efficacy, but a positive outcome with medical or
      surgical anti-reflux treatment has been reported by several studies of HE
      patients. Therefore, we believe that patients with endoscopy-negative heartburn
      should be investigated by means of impedance-pH monitoring with analysis of PSPW
      index and MNBI: such an approach provides accurate identification of HE cases,
      who remain, in our opinion, within the realm of GERD and should be treated
      accordingly.

PMID- 29333062
TI  - Helicobacter pylori infection and esophageal adenocarcinoma: a review and a
      personal view.
AB  - Esophageal adenocarcinoma (EAC) is etiologically associated with gastroesophageal
      reflux disease (GERD). There is evidence to support the sequence GERD, Barrett's
      esophagus (BE), dysplasia, and finally EAC, with Helicobacter pylori (H. pylori)
      being implicated in each step to EAC. On the other side of this relation stands
      the hypothesis of the protective role of H. pylori against EAC. Based on this
      controversy, our aim was to review the literature, specifically original clinical
      studies and meta-analyses linking H. pylori infection with EAC, but also to
      provide our personal and others' relative views on this topic. From a total of
      827 articles retrieved, 10 original clinical studies and 6 meta-analyses met the
      inclusion criteria. Original studies provided inconclusive data on an inverse or
      a neutral association between H. pylori infection and EAC, whereas meta-analyses
      of observational studies favor an inverse association. Despite these data, we
      consider that the positive association between H. pylori infection and GERD or
      BE, but not EAC, is seemingly a paradox. Likewise, the oncogenic effect of H.
      pylori infection on gastric and colon cancer, but not on EAC, also seems to be a
      paradox. In this regard, well-designed prospective cohort studies with a powered
      sample size are required, in which potential confounders should be taken into
      consideration since their design.

PMID- 29333063
TI  - Familial and ethnic risk in inflammatory bowel disease.
AB  - Familial aggregation in inflammatory bowel disease (IBD) has been established for
      several decades, reflecting shared genetic and environmental susceptibility. A
      positive family history remains the strongest recognizable risk factor for the
      development of IBD and is reported in around 8-12% of IBD patients. Crohn's
      disease shows a more frequent familial pattern than ulcerative colitis. The risk
      of developing IBD in first-degree relatives of an affected proband is increased 4
      to 8-fold. The risk for twins and children born from couples who both have IBD
      is also substantially higher; a cumulative effect of the number of family members
      affected has been described, with the highest incidence being described for
      families with three or more affected members. Herein, we review the available
      evidence regarding familial IBD, and briefly discuss the variation of IBD across
      different races and ethnicities, hoping to provide a useful update and a
      practical guide that can serve clinicians as a guide for counseling.

PMID- 29333064
TI  - Colorectal polyposis and inherited colorectal cancer syndromes.
AB  - The majority of colorectal cancer (CRC) cases are sporadic, with hereditary
      factors contributing to approximately 35% of CRC cases. Less than 5% of CRC is
      associated with a known genetic syndrome. Although adenomatous polyposis
      syndromes, hamartomatous polyposis syndromes, and those previously classified as
      non-polyposis CRC syndromes are quite rare, it is important for clinicians to
      know the characteristics of each syndrome and to understand the differences in
      cancer risks between the different conditions. This information is very important
      when treatment and surveillance plans are formulated for each individual patient.

PMID- 29333065
TI  - Hepatitis C infection in patients with hereditary bleeding disorders:
      epidemiology, natural history, and management.
AB  - Hereditary bleeding disorders include a group of diseases with abnormalities of
      coagulation. Prior to 1990, infection with hepatitis C virus (HCV) was mainly
      transmitted via pooled plasma products as a treatment for hereditary bleeding
      disorders. Anti-HCV positivity in these patients may be as high as >70% in some
      areas, while some of them have also been coinfected with human immunodeficiency
      virus. Since about 20% of HCV-infected patients clear the infection naturally,
      chronic HCV infection represents a significant health problem in this group of
      patients. Mortality due to chronic HCV infection is estimated to be >10 times
      higher in patients with hemophilia than in the general population, and is mainly
      due to liver cirrhosis and hepatocellular carcinoma. The antiviral treatment of
      HCV in patients with hereditary bleeding disorders is not different from that of
      any other infected patients. Nevertheless, many patients with hereditary bleeding
      disorders have declined (Peg)interferon-based treatment because of side effects.
      In recent years, multiple orally administrated direct-acting antivirals (DAAs)
      have been approved for HCV treatment. Unfortunately, there is not much experience
      from treating these patients with DAA regimens, as major studies and real-life
      data did not include adequate numbers of patients with inherited hemorrhagic
      disorders. However, the available data indicate that DAAs have an excellent
      safety profile with a sustained virological response rate of >90%.

PMID- 29333067
TI  - Complications of staple line and anastomoses following laparoscopic bariatric
      surgery.
AB  - With over 600 million people being obese, and given the scientific demonstration
      of the advantages of surgical treatment, bariatric surgery is on the rise. The
      promising long-term results in terms of weight loss, and particularly in relation
      to comorbidities and the control/cure rate, mean that the number of procedures
      performed in all countries remains high. However, the risk of potentially complex
      or fatal complications, though small, is present and is related to the procedures
      per se. This review is a guide for bariatric and/or general surgeons, offering a
      complete overview of the pathogenesis of anastomosis and staple line following
      the most common laparoscopic bariatric procedures: sleeve gastrectomy, gastric
      bypass, and mini-gastric bypass. The review is divided according to the procedure
      and the complications (leak, bleeding and stenosis), and evaluates all the
      factors that can potentially improve or worsen the complication rate,
      representing a "unicum" in the present literature on bariatric surgery.

PMID- 29333069
TI  - Comparison of strategies and goals for treatment of chronic constipation among
      gastroenterologists and general practitioners.
AB  - Background: Although guidelines have been published for the treatment of chronic
      constipation, little is known about the actual treatment strategies, the
      definitions of drug efficacy, the parameters for drug selection, and the
      conceived limitations of the available treatments. The purpose of this study was
      to address these issues by comparing treatment strategies among gastroenterology
      specialists (GIs) and general practitioners (GPs). Methods: An internet survey
      was sent nationwide and at random to GIs and GPs in order to define treatment
      strategies, drug efficacy, main parameters for drug selections and the main
      limitations of the available drug therapy. Results: Forty GIs and 132 GPs
      answered the survey. The maximal sample error was +/-13.4% and +/-8.8%. Treatment
      strategies varied considerably between GPs and GIs. The major parameters for drug
      selection were related to drug safety among GIs and to clinical outcome among
      GPs. The conceived limitations of drug therapy included lack of experience and
      unwanted side effects. Conclusions: Awareness of the possible treatment options
      and the recommended order of prescription differs between GIs and GPs. There are
      still unmet needs for optimizing the treatment for chronic constipation.

PMID- 29333068
TI  - Nab-paclitaxel as second-line treatment in advanced gastric cancer: a multicenter
      phase II study of the Hellenic Oncology Research Group.
AB  - Background: This study evaluated the safety and efficacy of nab-paclitaxel as
      second-line treatment in patients with advanced gastric adenocarcinoma. Methods:
      Thirty-nine pretreated patients [33 with taxane-based regimens (docetaxel,
      cisplatin, and fluorouracil)] and 6 with combination of fluoropyrimidines plus
      cisplatin with locally advanced inoperable and metastatic gastric and
      gastroesophageal junction adenocarcinoma were treated with weekly nab-paclitaxel
      (150 mg/m2 d1, d8, d15 in cycles of 28 days). Results: Partial response (PR) was
      documented in nine patients (23.1%; 95% confidence interval 10.1-37.2%), stable
      disease (SD) in 11 (28.2%) and disease progression in 18 (46.2%). The disease
      control rate (SD + PR + complete response) was 51.3%. Grade 3 and 4 neutropenia
      occurred in 10.2% and 5.1% of patients, respectively; grade 3 anemia in 5.1%;
      grade 3 neurotoxicity in 5.1%; and grade 2 pain in 5.1%. The median progression
      free survival was 3.0 months (range 0.3-13.6) and the median overall survival 6.8
      months (range 0.3-22). Conclusion: Nab-paclitaxel as second-line treatment in
      locally advanced inoperable or metastatic gastric and gastroesophageal junction
      carcinoma is an active chemotherapy regimen with a manageable toxicity profile
      and merits further evaluation.

PMID- 29333066
TI  - New insights into cholangiocarcinoma: multiple stems and related cell lineages of
      origin.
AB  - Cholangiocarcinoma (CCA) is a heterogeneous group of malignancies that may
      develop at any level of the biliary tree. CCA is currently classified into
      intrahepatic (iCCA), perihilar (pCCA) and distal (dCCA) on the basis of its
      anatomical location. Notably, although these three CCA subtypes have common
      features, they also have important inter- and intra-tumor differences that can
      affect their pathogenesis and outcome. A unique feature of CCA is that it
      manifests in the hepatic parenchyma or large intrahepatic and extrahepatic bile
      ducts, furnished by two distinct stem cell niches: the canals of Hering and the
      peribiliary glands, respectively. The complexity of CCA pathogenesis highlights
      the need for a multidisciplinary, translational, and systemic approach to this
      malignancy. This review focuses on advances in the knowledge of CCA
      histomorphology, risk factors, molecular pathogenesis, and subsets of CCA.

PMID- 29333070
TI  - Bacterial infections in patients with liver cirrhosis: clinical characteristics
      and the role of C-reactive protein.
AB  - Background: The diagnosis of bacterial infection in cirrhotic patients may be
      difficult, because of the absence of classical signs such as fever and raised
      white blood cell count. The role of C-reactive protein (CRP) in this context has
      not been clearly defined. Methods: Clinical and laboratory characteristics of 210
      consecutive cirrhotic patients with (n=100) or without (n=110) bacterial
      infection were compared with a control group of non-cirrhotic patients with
      infection (n=106). Results: Significantly fewer patients with cirrhosis had a
      body temperature >=37 degrees C when presenting with bacterial infection (56%
      cirrhotic vs. 85.5% non-cirrhotic patients, P=0.01). Mean leukocyte count was
      6.92 * 103/mm3 in patients with cirrhosis and infection, 5.75 * 103/mm3 (P=0.02)
      in cirrhotic patients without infection, and 11.28 * 103/mm3 in non-cirrhotic
      patients with infection (P<0.001). Multivariate analysis revealed that CRP level
      and model for end-stage liver disease score were significantly associated with
      the presence of infection in patients with cirrhosis. A cutoff level of CRP>10
      mg/L indicated the presence of infection with a sensitivity of 68%, a specificity
      of 84.5% and an area under the receiver operating characteristic curve of 0.8197.
      CRP cutoff level differed according to the severity of the liver disease: Child
      Pugh score (CPS) A: 21.3 mg/L, B: 17 mg/L, and C: 5.78 mg/L. Conclusions: CRP at
      admission could help diagnose infection in cirrhotic patients. Since the severity
      of liver disease seems to affect the CRP values, lower CRP levels might indicate
      infection. Clinical suspicion is necessary to avoid delay in diagnosis and
      initiate antibiotic treatment.

PMID- 29333071
TI  - Factors associated with waiting time on the liver transplant list: an analysis of
      the United Network for Organ Sharing (UNOS) database.
AB  - Background: Liver transplantation (LT) is an important treatment for acute liver
      failure and end-stage liver disease. In 2002, the model for end-stage liver
      disease (MELD) score was incorporated to prioritize patients awaiting LT.
      Although there is data on how the MELD score affects waiting times, there is a
      paucity of literature regarding other components. We aimed to evaluate the
      factors affecting LT waiting times in the United States. Methods: Using the
      United Network for Organ Sharing (UNOS) database, patients aged 12-75 years
      listed for LT over the years 2002-2015 were included. Variables tested in the
      model included patient characteristics, pertinent laboratory values, ABO blood
      type, region of listing, primary payer, ethnicity, and listing for simultaneous
      transplantation. Results: A total of 75,771 patients were included in the final
      analysis. The components of the MELD score were associated with shorter waiting
      times. Other factors associated with shorter waiting times were the need of
      mechanical ventilation and region 3 of transplantation. ABO blood type, primary
      payer, and placement of a transjugular intrahepatic porto-systemic shunt also
      influenced time on the LT waiting list. Conclusions: MELD score is utilized in
      the prioritization of liver allocation, and was expected to predict waiting-list
      time. Mechanical ventilation and other markers of disease severity are associated
      with higher MELD scores and thus shorter waiting times. Further research is
      needed to address reasons for the variation in waiting times between regions and
      payment systems in an attempt to decrease time to LT, standardize the listing
      process, and improve patient outcomes.

PMID- 29333073
TI  - The impact of age on the incidence and severity of post-endoscopic retrograde
      cholangiopancreatography pancreatitis.
AB  - Background: With advancing age there is progressive pancreatic atrophy and
      fibrosis, leading to tissue destruction and chronic pancreatitis that has been
      found to be protective against post-endoscopic retrograde
      cholangiopancreatography (ERCP) pancreatitis (PEP). However, there are no reports
      regarding the potential effect of the aging pancreatic changes on the incidence
      and severity of PEP. Therefore, the aim of the present study was to investigate
      the impact of senile changes in the pancreas on the incidence and severity of
      PEP. Methods: A total of 2688 patients who underwent the first therapeutic ERCP
      at a single center were included in the final analysis of the study. Patients
      were classified into two groups: 1644 patients aged <=75 years (mean age
      61.56+1.26 years), group A; and 1044 patients aged >75 years (mean age 81.97+4.29
      years), group B. Patients' files were identified using a retrospective database
      linked to the endoscopy reporting system. Patients' characteristic, endoscopic
      findings, details of intervention and rate and severity of PEP were evaluated.
      Results: No significant differences between the two groups were observed with
      regard to ERCP indication, patient- and technique-related risk factors for PEP,
      presence of periampullary diverticulum, and type of therapeutic intervention. The
      incidence of PEP was 5.2% in group A and 4% in group B (P=NS) with comparable
      grades of severity. All episodes of pancreatitis had full recovery with
      conventional treatment. One death occurred from respiratory arrest in each group
      of patients. Conclusion: This study shows that the pancreatic changes associated
      with aging do not influence the incidence and severity of PEP.

PMID- 29333072
TI  - Prevalence of incidental pancreatic cyst on upper endoscopic ultrasound.
AB  - Background: This study aimed to determine the prevalence of incidental pancreatic
      cysts in patients undergoing upper endoscopic ultrasound without a known
      pancreatic abnormality. Methods: This prospective study was conducted in two
      hospitals in Spain and enrolled consecutive patients referred for upper
      endoscopic ultrasound for a condition unrelated to the pancreas. Patients with a
      previous pancreatic anomaly, history of acute or chronic pancreatitis, evidence
      of acute pancreatitis, previous upper gastrointestinal surgery, or chronic
      abdominal pain suggestive of pancreatic origin were excluded. Univariate logistic
      regression was performed to evaluate individual covariates and the incidental
      pancreatic cyst risk. Results: A total of 298 patients were included, of whom 64
      had pancreatic cysts (21.5%; 16.9-26.6%). The mean size of the cysts was 6.3+/
      3.7 (range 3-25) mm. Six cysts (2%) were >10 mm and 16 (5.4%) were compatible
      with branch duct intraductal papillary mucinous neoplasm. The pancreatic cyst
      prevalence was similar in the two hospitals and increased significantly with age.
      Conclusion: The prevalence of incidental pancreatic cysts during endoscopic
      ultrasound was very high in our study population.

PMID- 29333074
TI  - Laparoendoscopic rendezvous may be an effective alternative to a failed
      preoperative endoscopic retrograde cholangiopancreatography in patients with
      cholecystocholedocholithiasis.
AB  - Background: Endoscopic retrograde cholangiopancreatography (ERCP), followed by
      laparoscopic cholecystectomy (LC), remains the standard way of management for
      patients with cholecystocholedocholithiasis. Laparoendoscopic rendezvous (LERV),
      a combined procedure for removing the gallbladder laparoscopically and clearing
      the common bile duct (CBD) endoscopically at the same time, could be an
      attractive alternative. The aim of this study was to compare LERV with classic
      ERCP in patients with cholecystocholedocholithiasis. Methods: 886 patients with
      cholecystocholedocholithiasis were treated either with the LERV technique (90
      patients), or with the 2-stage approach, which includes preoperative ERCP
      followed by LC (796 patients). The primary endpoint was any difference in the
      success of CBD cannulation and clearance; secondary endpoints were the detection
      of differences in morbidity (especially post-ERCP pancreatitis [PEP]), and the
      feasibility of the two approaches. Results: Successful cannulation of the CBD was
      more frequent with conventional ERCP compared with the LERV technique (89.8% vs.
      75.5%, P=0.0001). LERV appears to be as effective as conventional ERCP for
      complete CBD clearance (85.5% vs. 82.8%, P<0.1). None of the patients in the LERV
      group had an episode of clinical PEP, whereas in the conventional ERCP group
      there were 23 episodes of PEP and one death. The median amylase level was higher
      in patients undergoing conventional ERCP group compared to patients in LERV
      group. Conclusion: Classic ERCP has a higher rate of successful CBD cannulation
      and a similar rate of CBD clearance compared to LERV.

PMID- 29333075
TI  - Safety and efficacy of extending a previous endoscopic sphincterotomy for the
      treatment of retained or recurrent common bile duct stones.
AB  - Background: The aim of the study was to evaluate the safety and efficacy of
      extending a previous endoscopic sphincterotomy (ES) in patients with retained or
      recurrent common bile duct (CBD) stones. Methods: Between 2001 and 2013,
      extension of a previous ES, for known or suspected CBD stones, was performed in
      118 patients (m/f, 53/65) with a median age of 74 (range: 31-91) years (group A).
      During the same period, ES was performed in 1064 patients with suspected or known
      choledocholithiasis (group B). The efficacy and complications of the extension
      (group A) were analyzed and a comparison was made between groups regarding
      complications. Results: Bile duct cannulation was straightforward in all patients
      in group A, while it was considered difficult in 49% of patients in group B.
      Complete clearance was achieved in 76/97 patients (78%) with CBD stones, after a
      mean of 1.18 attempts per patient. Mechanical lithotripsy was required in 10% of
      patients. After extension, immediate bleeding occurred in 24 patients (20%),
      which stopped spontaneously in 9 (37%) and endoscopic hemostasis was required in
      the remainder. Complications were more frequent in group B (5.3% vs. 0.8%,
      P=0.031), but there was no significant difference for any individual
      complication. Immediate bleeding was more common in group B (29% vs. 20%,
      P=0.035), but there was no difference in clinical bleeding. Conclusion: Extension
      of a previous ES seems to be a simple, effective and safe technique, allowing
      stone clearance in nearly 80% of patients; it is thus recommended in patients
      with CBD stones after ES.

PMID- 29333077
TI  - Underwater endoclip closure after endoscopic resection for duodenal adenomas.

PMID- 29333076
TI  - Parenchyma-sparing hepatectomy (PSH) versus non-PSH for bilobar liver metastases
      of colorectal cancer.
AB  - Background: Preoperative interventions have increased the resectability of
      colorectal cancer (CRC) liver metastases. This retrospective study compares
      outcomes after liver resection for bilobar CRC metastases between patients who
      underwent parenchyma-sparing hepatectomy (PSH), i.e., segmentectomies and smaller
      resections on both lobes, and those treated with non-PSH, i.e., hemihepatectomy
      plus any resection on the other lobe. Methods: A cohort of 119 patients who
      underwent liver resection for bilobar CRC metastases were included. Perioperative
      course and long-term survival were compared between 59 patients who underwent PSH
      and 60 patients who underwent non-PSH. Statistical analyses were done using
      Pearson's chi-square test, Fisher's exact test and the Mann-Whitney U test.
      Overall survival analysis was performed by the Kaplan-Meier estimator and Cox
      regression analysis. Results: The median number of liver metastases was 2 in
      patients treated with PSH and 3 in those treated with non-PSH (P<0.01).
      Postoperative mortality, severe complications and radicality did not differ
      significantly between groups. Median intraoperative bleeding was 250 mL for PSH
      and 600 mL for non-PSH (P<0.001). Median operation time and hospital stay were
      significantly shorter for PSH. Overall survival was comparable between groups,
      also after adjustment for covariates. Conclusions: There were no significant
      differences in outcome, except for differences in bleeding, operation time and
      postoperative stay, favoring PSH. Furthermore, minimizing resection did not
      influence radicality. Hence, this study supports the use of PSH for bilobar CRC
      liver metastases when possible.

PMID- 29333078
TI  - Acute pancreatitis caused by cytomegalovirus-associated duodenal papillitis.

PMID- 29333079
TI  - Type 1 autoimmune hepatitis presenting with severe autoimmune neutropenia.
AB  - Autoimmune hepatitis (AIH) is a progressive, chronic liver disease characterized
      by unresolving hepatocellular inflammation of autoimmune origin. The clinical
      spectrum may vary from asymptomatic presentation, to non-specific symptoms such
      as fatigue, arthralgias, nausea and abdominal pain, to acute severe liver
      disease. AIH is characterized by the presence of interface hepatitis and portal
      plasma cell infiltration on histological examination, hypergammaglobulinemia, and
      positive autoantibodies. AIH is associated with other autoimmune diseases and its
      course is often accompanied by various non-specific hematological disorders.
      However, the coexistence of autoimmune neutropenia (AIN) is infrequent. We
      present a case of a female patient diagnosed with type 1 AIH and agranulocytosis
      on presentation. A diagnosis of AIN was established, based on the patient's sex,
      the underlying liver disease, the absence of alternative causes, the presence of
      atypical anti-neutrophil cytoplasmic antibodies in patient's serum and the
      favorable and dose-dependent treatment of both pathologic entities with
      corticosteroids and mycophenolate mofetil.

PMID- 29333080
TI  - Comparisons of Traffic-Related Ultrafine Particle Number Concentrations Measured
      in Two Urban Areas by Central, Residential, and Mobile Monitoring.
AB  - Traffic-related ultrafine particles (UFP; <100 nanometers diameter) are
      ubiquitous in urban air. While studies have shown that UFP are toxic,
      epidemiological evidence of health effects, which is needed to inform risk
      assessment at the population scale, is limited due to challenges of accurately
      estimating UFP exposures. Epidemiologic studies often use empirical models to
      estimate UFP exposures; however, the monitoring strategies upon which the models
      are based have varied between studies. Our study compares particle number
      concentrations (PNC; a proxy for UFP) measured by three different monitoring
      approaches (central-site, short-term residential-site, and mobile on-road
      monitoring) in two study areas in metropolitan Boston (MA, USA). Our objectives
      were to quantify ambient PNC differences between the three monitoring platforms,
      compare the temporal patterns and the spatial heterogeneity of PNC between the
      monitoring platforms, and identify factors that affect correlations across the
      platforms. We collected >12,000 hours of measurements at the central sites, 1,000
      hours of measurements at each of 20 residential sites in the two study areas, and
      >120 hours of mobile measurements over the course of ~1 year in each study area.
      Our results show differences between the monitoring strategies: mean one-minute
      PNC on-roads were higher (64,000 and 32,000 particles/cm3 in Boston and Chelsea,
      respectively) compared to central-site measurements (23,000 and 19,000
      particles/cm3) and both were higher than at residences (14,000 and 15,000
      particles/cm3). Temporal correlations and spatial heterogeneity also differed
      between the platforms. Temporal correlations were generally highest between
      central and residential sites, and lowest between central-site and on-road
      measurements. We observed the greatest spatial heterogeneity across monitoring
      platforms during the morning rush hours (06:00-09:00) and the lowest during the
      overnight hours (18:00-06:00). Longer averaging times (days and hours vs.
      minutes) increased temporal correlations (Pearson correlations were 0.69 and 0.60
      vs. 0.39 in Boston; 0.71 and 0.61 vs. 0.45 in Chelsea) and reduced spatial
      heterogeneity (coefficients of divergence were 0.24 and 0.29 vs. 0.33 in Boston;
      0.20 and 0.27 vs. 0.31 in Chelsea). Our results suggest that combining stationary
      and mobile monitoring may lead to improved characterization of UFP in urban areas
      and thereby lead to improved exposure assignment for epidemiology studies.

PMID- 29333081
TI  - Innate immunity recovers earlier than acquired immunity during severe
      postoperative immunosuppression.
AB  - Background: Postoperative immune suppression, particularly a loss of cell
      mediated immunity, is commonly seen after surgery and is associated with worse
      outcome, i.e. delayed wound healing, infections, sepsis, multiple-organ failure
      and cancer recurrence. However, the recovery of immune cells focusing on
      differences between innate and acquired immunity during severe postoperative
      immunosuppression is not investigated. Methods: In this retrospective randomized
      controlled trial (RCT) subgroup analysis, 10 postoperatively immune suppressed
      patients after esophageal or pancreatic resection were analyzed. Innate and
      acquired immune cells, the expression of human leukocyte antigen-D related on
      monocytes (mHLA-DR), lipopolysaccharide (LPS)-induced monocytic TNF-alpha and IL
      10 secretion ex vivo, Concanavalin A (Con A)-induced IFN-gamma, TNF-alpha, IL-2,
      IL-4, IL-5 and IL-10 release were measured preoperatively (od) until day 5 after
      surgery (pod5). Recovery of immune cells was defined by a significant decrease
      respectively increase after a significant postoperative alteration. Statistical
      analyses were performed using nonparametric statistical procedures. Results:
      Postoperative alterations of innate immune cells recovered on pod2 (eosinophils),
      pod3 (neutrophils) and pod5 (mHLA-DR, monocytic TNF-alpha and IL-10 secretion),
      whereas alterations of acquired immune cells (lymphocytes, T cells, T helper
      cells, and cytotoxic T cells) did not recover until pod5. Peripheral blood T
      cells showed an impaired production of the T helper (Th) 1 cytokine IFN-gamma
      upon Con A stimulation on pod1, while Th2 specific cytokine release did not
      change until pod5.Conclusions: Innate immunity recovered earlier than acquired
      immunity during severe postoperative immunosuppression. Furthermore, we found a
      more anti- than pro-inflammatory T cell function on the first day after surgery,
      while T cell counts decreased.

PMID- 29333082
TI  - A FCGR3A Polymorphism Predicts Anti-drug Antibodies in Chronic Inflammatory Bowel
      Disease Patients Treated With Anti-TNF.
AB  - BACKGROUND: The production of anti-drug antibodies (ADAs) against IgG monoclonal
      antibodies (mAbs) targeting tumour necrosis factor (TNF) is an important cause of
      loss of response to anti-TNF mAbs in patients with inflammatory bowel diseases
      (IBD) such as Crohn's disease (CD) and ulcerative colitis (UC). Since receptors
      for the Fc portion of IgG (FCGRs) are involved in the degradation of IgG
      complexes, we hypothesised that a polymorphism in FCGR3A (V158F; rs396991) gene
      could be involved in anti-TNF ADA generation and treatment resistance. MATERIAL
      AND METHODS: A cohort of 103 IBD patients (80 CD, 23 UC) were genotyped and serum
      level of both anti-TNFs (infliximab or adalimumab) and ADA against them were
      measured. RESULTS: No significant differences were observed between ADA
      occurrence or V158F genotype and type of disease or the kind of anti-TNF
      administrated. Interestingly, VV genotype correlated with patients producing ADA
      (VV: 37.5% vs. FV: 10.6% or FF: 5%; p=0.004) and was an independent predictor of
      this event after multivariate analysis. Moreover, VV genotype also correlated
      with those patients receiving anti-TNF dose intensification (p=0.03). CONCLUSION:
      FCGR3A V158F polymorphism seems to be associated with ADA production against mAbs
      and it could be taken into account when considering the dose and type of anti-TNF
      in IBD patients.

PMID- 29333083
TI  - Optimal Load for Bone Tissue Scaffolds with an Assigned Geometry.
AB  - Thanks to the recent advances of three-dimensional printing technologies the
      design and the fabrication of a large variety of scaffold geometries was made
      possible. The surgeon has the availability of a wide number of scaffold micro
      architectures thus needing adequate guidelines for the choice of the best one to
      be implanted in a patient-specific anatomic region. We propose a mechanobiology
      based optimization algorithm capable of determining, for bone tissue scaffolds
      with an assigned geometry, the optimal value Lopt of the compression load to
      which they should be subjected, i.e. the load value for which the formation of
      the largest amounts of bone is favoured and hence the successful outcome of the
      scaffold implantation procedure is guaranteed. Scaffolds based on hexahedron unit
      cells were investigated including pores differently dimensioned and with
      different shapes such as elliptic or rectangular. The algorithm predicted
      decreasing values of the optimal load for scaffolds with pores with increasing
      dimensions. The optimal values predicted for the scaffolds with elliptic pores
      were found higher than those with rectangular ones. The proposed algorithm can be
      utilized to properly guide the surgeon in the choice of the best scaffold
      type/geometry that better satisfies the specific patient requirements.

PMID- 29333084
TI  - Effects of alpha-Mangostin on Viability, Growth and Cohesion of Multicellular
      Spheroids Derived from Human Breast Cancer Cell Lines.
AB  - Background: alpha-Mangostin (alphaMG) is extracted from Garcinia mangostana Linn
      and exerts antiproliferative activities. Although several researches on alphaMG
      were performed using cell monolayers, the in vitro pharmacological effects on 3D
      cancer models have never been investigated. Aim of the present study was to find
      new anticancer properties of alphaMG by evaluating the changes that this compound
      provokes in multicellular tumour spheroids (MCTSs). Methods: MCTSs were generated
      from MDA-MB-231 and MCF-7 breast tumour cell lines and then treated with 0.1/30
      MUg/ml alphaMG for 24 and 48 h. MCTS size, density, and cell migration were
      determined by software elaboration of phase contrast images captured by a digital
      camera. Cell viability was evaluated by resazurin and acid phosphatase assays,
      while cell apoptosis was assessed by a fluorescent assay of caspase activity. The
      distribution of living cells inside MCTSs was shown by live/dead fluorescence
      staining. Results: A dose-dependent decrease in cell viability was obtained by
      treating MDA-MB-231 spheroids with alphaMG for 48 h (IC50 = 0.70-1.25 MUg/ml). A
      significant reduction in spheroid volume, paralleled by its increased
      compactness, was observed only at concentration of 30 MUg/ml, but not with lower
      doses of alphaMG. By contrast, alphaMG in the range of 5-15 MUg/ml increased the
      size of MCTSs due to a parallel reduction in cell aggregation. The same window of
      concentrations was also able to stimulate cell apoptosis in a dose-dependent
      manner. Bimodal volumetric effects were also obtained by treating the spheroids
      generated from the MCF-7 cells with 0.1/30 MUg/ml alphaMG for 48 h. Finally,
      doses higher than 5 MUg/ml caused a progressive impairment in cell migration from
      the edge of MDA-MB-231 MCTSs. Conclusion: After exposure at doses of alphaMG just
      above IC50, MDA-MB-231 spheroids showed a significant reduction in cell adhesion
      that did not stimulate cell migration but, on the contrary, blunted cell
      motility. These findings suggest a novel anticancer feature of alphaMG that could
      be taken into consideration to improve conventional drug penetration into the
      tumour bulk.

PMID- 29333085
TI  - Next Generation Sequencing expression profiling of mitochondrial subunits in men
      with Klinefelter syndrome.
AB  - Objectives: Klinefelter syndrome (KS) is one of the most common sex-chromosome
      disorders as it affects up to 1 in every 600-1000 newborn males. Men with KS
      carry one extra X chromosome and they usually present a 47,XXY karyotype, but
      less frequent variants have also been reported in literature. KS typical symptoms
      include tall stature, gynecomastia, broad hips, hypogonadism and absent
      spermatogenesis. The syndrome is also related to a wide range of cognitive
      deficits, among which language-based learning disabilities and verbal cognition
      impairment are frequently diagnosed. The present study was carried out to
      investigate the role of mitochondrial subunits in KS, since the molecular
      mechanisms underlying KS pathogenesis are not fully understood. Methods: The
      study was performed by the next generation sequencing analysis and qRT-PCR assay.
      Results: We were able to identify a significant down-expression of mitochondrial
      encoded NADH: ubiquinone oxidoreductase core subunit 6 (MT-ND6) in men with KS.
      Conclusion: It is known that defects of the mtDNA encoding mitochondrial subunits
      are responsible for the malfunction of Complex I, which will eventually lead to
      the Complex I deficiency, the most common respiratory chain defect in human
      disorders. Since it has been shown that decreased Complex I protein levels could
      induce apoptosis, wehypothesizethat the above-mentioned MT-ND6 down-expression
      contributes to the wide range of phenotypes observed in men with KS.

PMID- 29333087
TI  - Antioxydation And Cell Migration Genes Are Identified as Potential Therapeutic
      Targets in Basal-Like and BRCA1 Mutated Breast Cancer Cell Lines.
AB  - Basal-like breast cancers are among the most aggressive cancers and effective
      targeted therapies are still missing. In order to identify new therapeutic
      targets, we performed Methyl-Seq and RNA-Seq of 10 breast cancer cell lines with
      different phenotypes. We confirmed that breast cancer subtypes cluster the RNA
      Seq data but not the Methyl-Seq data. Basal-like tumor hypermethylated phenotype
      was not confirmed in our study but RNA-Seq analysis allowed to identify 77 genes
      significantly overexpressed in basal-like breast cancer cell lines. Among them,
      48 were overexpressed in triple negative breast cancers of TCGA data. Some
      molecular functions were overrepresented in this candidate gene list. Genes
      involved in antioxydation, such as SOD1, MGST3 and PRDX or cadherin-binding
      genes, such as PFN1, ITGB1 and ANXA1, could thus be considered as basal like
      breast cancer biomarkers. We then sought if these genes were linked to BRCA1,
      since this gene is often inactivated in basal-like breast cancers. Nine genes
      were identified overexpressed in both basal-like breast cancer cells and BRCA1
      mutated cells. Amongst them, at least 3 genes code for proteins implicated in
      epithelial cell migration and epithelial to mesenchymal transition (VIM, ITGB1
      and RhoA). Our study provided several potential therapeutic targets for triple
      negative and BRCA1 mutated breast cancers. It seems that migration and
      mesenchymal properties acquisition of basal-like breast cancer cells is a key
      functional pathway in these tumors with a high metastatic potential.

PMID- 29333086
TI  - Ethical and Safety Issues of Stem Cell-Based Therapy.
AB  - Results obtained from completed and on-going clinical studies indicate huge
      therapeutic potential of stem cell-based therapy in the treatment of
      degenerative, autoimmune and genetic disorders. However, clinical application of
      stem cells raises numerous ethical and safety concerns. In this review, we
      provide an overview of the most important ethical issues in stem cell therapy, as
      a contribution to the controversial debate about their clinical usage in
      regenerative and transplantation medicine. We describe ethical challenges
      regarding human embryonic stem cell (hESC) research, emphasizing that ethical
      dilemma involving the destruction of a human embryo is a major factor that may
      have limited the development of hESC-based clinical therapies. With previous
      derivation of induced pluripotent stem cells (iPSCs) this problem has been
      overcome, however current perspectives regarding clinical translation of iPSCs
      still remain. Unlimited differentiation potential of iPSCs which can be used in
      human reproductive cloning, as a risk for generation of genetically engineered
      human embryos and human-animal chimeras, is major ethical issue, while undesired
      differentiation and malignant transformation are major safety issues. Although
      clinical application of mesenchymal stem cells (MSCs) has shown beneficial
      effects in the therapy of autoimmune and chronic inflammatory diseases, the
      ability to promote tumor growth and metastasis and overestimated therapeutic
      potential of MSCs still provide concerns for the field of regenerative medicine.
      This review offers stem cell scientists, clinicians and patient's useful
      information and could be used as a starting point for more in-depth analysis of
      ethical and safety issues related to clinical application of stem cells.

PMID- 29333088
TI  - Bone Regeneration using Silk Hydroxyapatite Hybrid Composite in a Rat Alveolar
      Defect Model.
AB  - Background: To overcome the limited source of autogenous bone in bone grafting,
      many efforts have been made to find bone substitutes. The use of hybrid
      composites of silk and hydroxyapatite to simulate natural bone tissue can
      overcome the softness and brittleness of the individual components. Methods:
      Critical-sized, 7 x 4 x 1.5 mm alveolar defects were created surgically in 36
      Sprague-Dawley rats. Three treatment groups were tested: an empty defect group
      (group I), a silk fibrin scaffold group (group II), and a hydroxyapatite
      conjugated silk fibrin scaffold group (group III). New bone formation was
      assessed using computed tomography and histology at 4, 8, and 12 weeks, and semi
      quantitative western blot analysis was done to confirm bone protein formation at
      12weeks. Statistical analysis of new bone formation was done using the Kruskal
      Wallis test. Results: Radiomorphometric volume analysis revealed that new bone
      formation was 64.5% in group I, 77.4% in group II, and 84.8% in group III
      (p=0.027) at 12 weeks. Histologically, the osteoid tissues were surrounded by
      osteoblasts not only at the border of the bone defect but in the center of the
      scaffold implanted area in group III from week 8 on. Semi-quantitative western
      blotting revealed that osteocalcin expression in group III was 1.8 times higher
      than group II and 2.6 times higher than group I. Conclusions: New bone formation
      was higher in hybrid scaffolds. Both osteoconduction at the defect margin and
      osteoinduction at the center of the defect were confirmed. There were no detected
      complications related to foreign body implantation.

PMID- 29333089
TI  - Lentivirus-mediated shRNA Targeting CNN2 Inhibits Hepatocarcinoma in Vitro and in
      Vivo.
AB  - Objective: Hepatocellular carcinoma (HCC) is one of the most common malignant
      tumors with a high rate of mortality. Our previous study shows the expression of
      calponin 2 (CNN2) is up-regulated in hepatocellular carcinoma tissues, especially
      in metastatic ones. To better understand the role of CNN2 in HCC, RNA
      interference (RNAi) was used to explore its role in tumor growth and metastasis.
      Methods: Lentivirus-mediated CNN2-shRNA was transfected into SK-hep-1 cells, and
      the efficacy of CNN2 expression, cell migration, invasion, proliferation and cell
      cycles were evaluated by quantitative real-time polymerase chain reaction (qRT
      PCR), Western blot (WB), Transwell assay, methyl thiazol tetrazolium assay and
      flow cytometry, respectively. SK-hep-1 cells transfected with Lentivirus-CNN2
      shRNA were xenografted in Balb/C nude mice to explore the effect of CNN2-shRNA in
      tumor growth. Xenograft tumor tissues were examined for their histopathology,
      cell apoptosis, the expression of total protein and their corresponding
      phosphorylated protein of MEK1/2, ERK1/2, AKT, by hematoxylin and eosin stain (H
      & E staining), TUNEL assay, immunohistochemical technique, respectively. Results:
      Our research shows it is evident that CNN2 shRNA can effectively down-regulate
      the expressions of CNN2 mRNA and protein, inhibit cell proliferations, arrest
      cell cycles at the S phase and reduce cell migration and invasion. SK-hep-1 cells
      with CNN2 down-regulation have markedly attenuated tumor growth in nude mice.
      Xenograft tumor tissues have displayed typical tumor characteristics and no
      apoptosis is detected in shRNA group or in control group. No metastatic tumor was
      found in any group of nude mice. With CNN2 protein down-regulation, the protein
      of pMEK1/2 and pERK1/2 are effectively down-regulated, except pAKT, AKT, MEK1/2
      and ERK1/2. Conclusions: CNN2 plays an important role in tumor growth and
      metastasis, possibly through MEK1/2-ERK1/2 signaling pathway. Our study
      illustrate that CNN2 might be a potential target in HCC molecular target therapy.

PMID- 29333090
TI  - Gene and Protein Expression Profiles in a Mouse Model of Collagen-Induced
      Arthritis.
AB  - The risk of rheumatoid arthritis (RA), an autoimmune disease, in the elderly
      population increases along with that of atherosclerosis, cardiovascular disease,
      type 2 diabetes, and Alzheimer's disease. Identifying specific biomarkers for RA
      can clarify the underlying molecular mechanisms and can aid diagnosis and patient
      care. To this end, the present study investigated the genes and proteins that are
      differentially expressed in RA using a mouse collagen-induced arthritis (CIA)
      model. We performed gene microarray and proteome array analyses using blood
      samples from the mice and found that 50 genes and 24 proteins were upregulated
      and 48 genes were downregulated by more than 2-fold in the CIA model relative to
      the control. The gene microarray and proteome array results were validated by
      evaluating the expression levels of select genes and proteins by real-time PCR
      and western blotting, respectively. We found that the level of integrin alpha2,
      which has not been previously reported as a biomarker of RA, was significantly
      increased in CIA mice as compared to controls. These findings provide a set of
      novel biomarkers that can be useful for diagnosing and evaluating the progression
      of RA.

PMID- 29333091
TI  - In vitro and in vivo effects of miRNA-19b/20a/92a on gastric cancer stem cells
      and the related mechanism.
AB  - We aimed to analyze the in vitro and in vivo effects of miRNA-19b/20a/92a on
      gastric cancer stem cells (GCSCs) and the related mechanism. GCSCs were cultured
      until adherence and differentiation, and subjected to miRNA microarray analysis
      to find and to verify miRNA deletion. Cells stably expressing lentivirus carrying
      miRNA-19b/20a/92a were constructed by transfection. The relationship between
      miRNA-19b/20a/92a and renewal of GCSCs was studied by the tumor sphere assay, and
      that between miRNA-19b/20a/92a and their proliferation was explored with MTT and
      colony formation assays. Target genes of miRNA for promoting the proliferation
      and self-renewal of GCSCs were found by using bioinformatics database, and
      verified by the reporter gene assay and Western blot. The expressions of miRNA
      19b/20a/92a gradually decreased during the adherence and differentiation of
      GCSCs. The expressions of lentivirus carrying miRNA-17-19 gene in MKN28 and CD44
      /EpCAM- cells were increased significantly. Transient transfection with pre-miRNA
      19b/20a/92a elevated miRNA expressions in CD44-/EpCAM- and MKN28 cells, whereas
      transfection with pre-miRNA-19b/20a/92a antagonists reduced the expressions in
      SGC7901 and CD44+/EpCAM+ cells. Overexpression of lenti-miRNA-19b/20a/92a
      significantly enhanced the capability of GCSCs to form tumor spheres. In the
      presence of chemotherapeutic agent, the survival of lenti-miRNA-19b/20a/92a
      infected cells was prolonged. Transient transfection with pre-miRNA-19b/20a/92a
      significantly increased the number of CD44+/EpCAM+ cells, but transfection with
      antagonists had the opposite outcomes. The stable miRNA-19b/20a/92a expression
      groups proliferated faster than the control group did. The proliferation of cells
      transfected with pre-miRNA-19b/20a/92a was accelerated, whereas that of cells
      transfected with the antagonists was decelerated. Compared with the control
      group, the number of colonies in the former group was higher, but that in the
      latter group was lower. miRNA-19b and miRNA-92a could bind the 3' untranslated
      region of HIPK1, while miRNA-20a was able to bind that of E2F1. Expressions of
      miRNA-20a and miRNA-92a in gastric cancer samples were negatively correlated with
      the prognosis of patients. miRNA-19b/20a/92a facilitated the self-renewal of
      GCSCs by targeting E2F1 and HIPK1 on the post-transcriptional level and
      activating the beta-catenin signal transduction pathway. miRNA-92a was an
      independent factor and index predicting the prognosis of gastric cancer.

PMID- 29333092
TI  - Role of APOBEC3H in the Viral Control of HIV Elite Controller Patients.
AB  - Background APOBEC3H (A3H) gene presents variation at 2 positions (rs139297 and
      rs79323350) leading to a non-functional protein. So far, there is no information
      on the role played by A3H in spontaneous control of HIV. The aim of this study
      was to evaluate the A3H polymorphisms distribution in a well-characterized group
      of Elite Controller (EC) subjects. Methods We analyzed the genotype distribution
      of two different SNPs (rs139297 and rs79323350) of A3H in 30 EC patients and
      compared with 11 non-controller (NC) HIV patients. Genotyping was performed by
      PCR, cloning and Sanger sequencing. Both polymorphisms were analyzed jointly in
      order to adequately attribute the active or inactive status of A3H protein.
      Results EC subjects included in this study were able to maintain a long-term
      sustained spontaneous HIV-viral control and optimal CD4-T-cell counts; however,
      haplotypes leading to an active protein were very poorly represented in these
      patients. We found that the majority of EC subjects (23/30; 77%) presented
      allelic combinations leading to an inactive A3H protein, a frequency slightly
      lower than that observed for NC studied patients (10/11; 91%). Conclusions The
      high prevalence of non-functional protein coding-genotypes in EC subjects seems
      to indicate that other innate restriction factors different from APOBEC3H could
      be implicated in the replication control exhibited by these subjects.

PMID- 29333093
TI  - Bactericidal effects of deep ultraviolet light-emitting diode for solutions
      during intravenous infusion.
AB  - Background: Ultraviolet irradiation is effectively used as a disinfection method
      for inactivating microorganisms. Methods: We investigated the bactericidal
      effects by irradiation with a deep-ultraviolet light-emitting diode (DUV-LED) on
      the causative microorganisms of catheter related blood stream infection
      contaminating the solution for intravenous infusion. For irradiation, prototype
      modules for water disinfection with a DUV-LED were used. Experiments were
      conducted on five kinds of microorganisms. We examined the dependence of
      bactericidal action on eleven solutions. Administration sets were carried out
      three types. Results: When the administration set JY-PB343L containing the
      infusion tube made of polybutadiene was used, the bactericidal action of the DUV
      LED against all tested microorganisms in the physiological saline solutions was
      considered to be effective. We confirmed that the number of viable bacteria
      decreased in 5% glucose solution and electrolyte infusions with DUV-LED
      irradiation. Conclusions: These results indicate that the DUV-LED irradiation has
      bactericidal effects in glucose infusion and electrolyte infusions by irradiating
      via a plasticizer-free polybutadiene administration set. We consider DUV-LED
      irradiation to be clinically applicable.

PMID- 29333094
TI  - Left ventricular diastolic and systolic dyssynchrony and dysfunction in heart
      failure with preserved ejection fraction and a narrow QRS complex.
AB  - Aims: Mechanical dyssynchrony has been reported in heart failure with preserved
      ejection fraction (HFpEF), with a majority of patients having a narrow QRS
      complex; however, whether any benefit is observed with restoration of
      dyssynchrony remains unclear. We sought to assess left ventricular (LV)
      dyssynchrony and function in HFpEF and elucidate the underlying mechanisms that
      may account for HFpEF. Methods: Seventy-eighty patients with a narrow QRS complex
      including 47 with HFpEF, 31 with heart failure with reduced ejection fraction
      (HFrEF) patients, and 29 with asymptomatic left ventricular diastolic dysfunction
      (LVDD) were recruited. Forty-five normal subjects acted as controls. Systolic LV
      longitudinal strain (LS), systolic longitudinal strain rate (LSrS), early
      diastolic longitudinal strain rate (LSrE), and late diastolic longitudinal strain
      rate (LSrA) were measured using speckle tracking echocardiography. LV diastolic
      and systolic dyssynchrony (Te-SD and Ts-SD) were calculated. Results: Te-SD and
      Ts-SD were prolonged in HFpEF and HFrEF patients than in the control group
      (p<0.05). However, Ts-SD was shorter in HFpEF patients compared to HFrEF patients
      despite a narrow QRS complex (p<0.05). LV global LS, LSrS, and LSrE were
      decreased in patients with HFpEF and HFrEF compared to other groups, with HFrEF
      being even more reduced than HFpEF (p<0.05). Reduced LS, LSrS, and LSrE could
      effectively differentiate HF from asymptomatic LVDD patients (p<0.05).
      Conclusion: HFrEF exhibited increased systolic dyssynchrony compared to HFpEF
      despite a narrow QRS complex in addition to the more reduced diastolic and
      systolic function. Therefore, targeting to improve diastolic and systolic
      function instead of managing systolic dyssynchrony might be of great importance
      in the treatment of HFpEF.

PMID- 29333095
TI  - Cinnamomum Cassia Extracts Suppress Human Lung Cancer Cells Invasion by Reducing
      u-PA/MMP Expression through the FAK to ERK Pathways.
AB  - Cinnamomum cassia exhibits antioxidative, apoptotic, and cytostatic properties.
      These activities have been attributed to the modulation of several biological
      processes and are beneficial for possible pharmaceutical applications. However,
      the potential of C. cassia in retarding lung adenocarcinoma cells metastasis
      remains ambiguous. We determined whether C. cassia extract (CCE) reduces
      metastasis of human lung adenocarcinoma cells. The results showed that CCE
      treatment (up to 60 MUg/mL) for 24 h exhibited no cytotoxicity on the A549 and
      H1299 cell lines but inhibited the motility, invasiveness, and migration of these
      cells by repressing matrix metalloproteinase (MMP)-2 and urokinase-type
      plasminogen activator (u-PA). CCE also impaired cell adhesion to collagen. CCE
      significantly reduced p-focal adhesion kinase (FAK) Tyr397, p-FAK Tyr925, p
      extracellular signal-regulated kinases (ERK)1/2, and Ras homolog gene family
      (Rho)A expression. CCE showed anti-metastatic activity of A549 and H1299 cells by
      repressing u-PA/MMP-2 via FAK to ERK1/2 pathways. These findings may facilitate
      future clinical trials of lung adenocarcinoma chemotherapy to confirm the
      promising results.

PMID- 29333096
TI  - Analysis of MED12 Mutation in Multiple Uterine Leiomyomas in South Korean
      patients.
AB  - Uterine leiomyomas are one of the most common benign gynecologic tumors, but the
      exact causes are not completely understood. In 2011, through DNA sequencing,
      MED12 mutation was discovered in approximately 71% of uterine leiomyomas. Several
      recent studies confirmed the high frequency of MED12 mutation in uterine
      leiomyoma. Nevertheless, no study has been done on MED12 mutation in the case of
      patients with multiple leiomyomas in a patient. The purpose of this study was to
      investigate the frequency of MED12 mutations in uterine leiomyomas of South
      Korean patients. In addition, we examined MED12 mutation in multiple leiomyomas
      in the same patients. Uterine leiomyoma tissues were obtained from symptomatic
      women who underwent hysterectomy or myomectomy for medically indicated reasons.
      We collected 60 uterine leiomyomas from 41 women. Tumor size ranged from 1 to
      12cm. Patients' ages ranged from 25 to 55 years with an average of 38.4 years. Of
      the 60 tumors, 40 (66.67%) displayed MED12 mutation. Among the 41 patients, 14
      patients had multiple leiomyomas and we analyzed those multiple leiomyomas. Three
      of them had the same mutations. Five of them, each leiomyoma had a different
      mutation. Two of them did not have mutation. Four of them had both mutation
      positive and mutation-negative leiomyomas. In conclusion, we confirmed the high
      frequency of the MED12 mutation in uterine leiomyomas of South Korean patients.
      We also identified various MED12 mutation status in patients with multiple
      leiomyomas. This suggests that in a given patient, different tumors may have
      arisen from different cell origins and therefore it is supposed that occurrence
      of multiple leiomyoma in a single patient may not be caused by intrauterine
      metastasis or dissemination.

PMID- 29333097
TI  - Preliminary Study of MR and Fluorescence Dual-mode Imaging: Combined Macrophage
      Targeted and Superparamagnetic Polymeric Micelles.
AB  - Purpose: To establish small-sized superparamagnetic polymeric micelles for
      magnetic resonance and fluorescent dual-modal imaging, we investigated the
      feasibility of MR imaging (MRI) and macrophage-targeted in vitro. Methods: A new
      class of superparamagnetic iron oxide nanoparticles (SPIONs) and Nile red-co
      loaded mPEG-Lys3-CA4-NR/SPION polymeric micelles was synthesized to label
      Raw264.7 cells. The physical characteristics of the polymeric micelles were
      assessed, the T2 relaxation rate was calculated, and the effect of labeling on
      the cell viability and cytotoxicity was also determined in vitro. In addition,
      further evaluation of the application potential of the micelles was conducted via
      in vitro MRI. Results: The diameter of the mPEG-Lys3-CA4-NR/SPION polymeric
      micelles was 33.8 +/- 5.8 nm on average. Compared with the hydrophilic SPIO, mPEG
      Lys3-CA4-NR/SPION micelles increased transversely (r2), leading to a notably high
      r2 from 1.908 ug/mL-1S-1 up to 5.032 ug/mL-1S-1, making the mPEG-Lys3-CA4
      NR/SPION micelles a highly sensitive MRI T2 contrast agent, as further
      demonstrated by in vitro MRI. The results of Confocal Laser Scanning Microscopy
      (CLSM) and Prussian blue staining of Raw264.7 after incubation with micelle
      containing medium indicated that the cellular uptake efficiency is high.
      Conclusion: We successfully synthesized dual-modal MR and fluorescence imaging
      mPEG-Lys3-CA4-NR/SPION polymeric micelles with an ultra-small size and high MRI
      sensitivity, which were effectively and quickly uptaken into Raw 264.7 cells.
      mPEG-Lys3-CA4-NR/SPION polymeric micelles might become a new MR lymphography
      contrast agent, with high effectiveness and high MRI sensitivity.

PMID- 29333098
TI  - MiR-22-3p Regulates Cell Proliferation and Inhibits Cell Apoptosis through
      Targeting the eIF4EBP3 Gene in Human Cervical Squamous Carcinoma Cells.
AB  - Background: MicroRNAs (miRNAs) are non-coding small RNAs that function as
      negative regulators of gene expression and are involved in tumour biology. The
      eIF4E-binding proteins (eIF4EBPs) play essential roles in preventing translation
      initiation and inhibiting protein synthesis at a global or message-specific level
      in a variety of tumours. Methods: According to comparative miRNA profiles of
      clinical cervical cancer and non-cancerous cervical tissue specimens, several
      miRNAs were aberrantly expressed in the cervical cancer samples. C33a and SiHa
      cell proliferation and apoptosis were detected using methyl thiazolyl tetrazolium
      (MTT) and flow cytometry assays, respectively. Results: Among the aberrantly
      expressed miRNAs, miR-22-3p was significantly differentially expressed in
      cervical cancer tissues and was highly associated with cervical cancer cell
      growth regulation. In addition, bioinformatic predictions and experimental
      validation were used to identify whether eIF4E-binding protein 3 (eIF4EBP3) was a
      direct target of miR-22-3p; eIF4EBP3 protein levels were generally low in the
      cervical cancer tissues. Furthermore, functional studies revealed that either a
      miR-22-3p inhibitor or eIF4EBP3 overexpression could induce apoptosis in cervical
      cancer cells in vitro. Importantly, we found that eIF4EBP3 accumulation could
      significantly attenuate cervical cancer cell proliferation triggered by a miR-22
      3p mimic as well as enhance apoptosis in cervical cancer cells. Conclusion: Taken
      together, our data provide primary proof that miR-22-3p can induce cervical
      cancer cell growth at least in part by up-regulating its expression to decrease
      eIF4EBP3 expression levels; miR-22-3p thus holds promise as a prognostic
      biomarker and potential therapeutic target for treating cervical cancer.

PMID- 29333099
TI  - Pulsed Radiofrequency Applied to the Sciatic Nerve Improves Neuropathic Pain by
      Down-regulating The Expression of Calcitonin Gene-related Peptide in the Dorsal
      Root Ganglion.
AB  - Background: Clinical studies have shown that applying pulsed radiofrequency (PRF)
      to the neural stem could relieve neuropathic pain (NP), albeit through an unclear
      analgesic mechanism. And animal experiments have indicated that calcitonin gene
      related peptide (CGRP) expressed in the dorsal root ganglion (DRG) is involved in
      generating and maintaining NP. In this case, it is uncertain whether PRF plays an
      analgesic role by affecting CGRP expression in DRG. Methods: Rats were randomly
      divided into four groups: Groups A, B, C, and D. In Groups C and D, the right
      sciatic nerve was ligated to establish the CCI model, while in Groups A and B,
      the sciatic nerve was isolated without ligation. After 14 days, the right sciatic
      nerve in Groups B and D re-exposed and was treated with PRF on the ligation site.
      Thermal withdrawal latency (TWL) and hindpaw withdrawal threshold (HWT) were
      measured before PRF treatment (Day 0) as well as after 2, 4, 8, and 14 days of
      treatment. At the same time points of the behavioral tests, the right L4-L6 DRG
      was sampled and analyzed for CGRP expression using RT-qPCR and an enzyme-linked
      immunosorbent assay (ELISA). Results: Fourteen days after sciatic nerve ligation,
      rats in Groups C and D had a shortened TWL (P<0.001) and a reduced HWT (P<0.001)
      compared to those in Groups A and B. After PRF treatment, the TWL of the rats in
      Group D gradually extended with HWT increasing progressively. Prior to PRF
      treatment (Day 0), CGRP mRNA expressions in the L4-L6 DRG of Groups C and D
      increased significantly (P<0.001) and were 2.7 and 2.6 times that of Group A
      respectively. ELISA results showed that the CGRP content of Groups C and D
      significantly increased in comparison with that of Groups A and B (P<0.01). After
      PRF treatment, the mRNA expression in the DRG of Group D gradually decreased and
      the mRNA expression was 1.7 times that of Group A on the 4th day(P> 0.05). On the
      8th and 14th days, the mRNA levels in Group D were restored to those of Groups A
      and B. Meanwhile, the CGRP content of Group D gradually dropped over time, from
      76.4 pg/mg (Day 0) to 57.5 pg/mg (Day 14). Conclusions: In this study, we found
      that, after sciatic nerve ligation, rats exhibited apparent hyperalgesia and
      allodynia, and CGRP mRNA and CGRP contents in the L4-L6 DRG increased
      significantly. Through lowering CGRP expression in the DRG, PRF treatment might
      relieve the pain behaviors of NP.

PMID- 29333100
TI  - Assessment of the Temporomandibular Joint Function in Young Adults without
      Complaints from the Masticatory System.
AB  - Objective of the study was to evaluate the clinical status of the masticatory
      system in young adults with full permanent dentition and no stomatognathic system
      complaints. The study involved 186 randomly selected people with full dental
      arches with normal occlusal conditions corresponding to Angle's Class I aged 18 -
      21 years with an average age of 19 years. Subjects were clinically examined and
      temporomandibular joint (TMJ) vibrations were recorded during open-wide and close
      movements using BioJVA. Then, patients were categorized into groups according to
      Piper's classification system. The TMJs of the subjects were categorized
      according to the values of the vibration energy and the Piper protocol. This
      detected 33.4% of the joints with loosened ligaments, subluxation in 8.28%,
      initial signs of disc dysfunction in 5.08% and disc displacement without locking
      in 1.6 %. Median frequency differed significantly (p < 0.05) between the group of
      subjects with initial signs of TMJ dysfunction and other groups. Peak Frequency
      differed significantly (p < 0.05) between the healthy joints and those with TMJ
      subluxation. In this group of young healthy people, the majority of study joints
      generated small vibrations. However, a subset of people manifested higher
      vibrations that may indicate an early stage of TMJ dysfunction. Median Frequency
      was an important parameter for detecting initial symptoms of TMJ dysfunction.
      Peak Frequency was an important characteristic parameter for detecting TMJ
      subluxation.

PMID- 29333101
TI  - Variations in the AURKA Gene: Biomarkers for the Development and Progression of
      Hepatocellular Carcinoma.
AB  - Hepatocellular carcinoma (HCC) is a liver malignancy and a major cause of cancer
      mortality worldwide. AURKA (aurora kinase A) is a mitotic serine/threonine kinase
      that functions as an oncogene and plays a critical role in hepatocarcinogenesis.
      We report on the association between 4 single nucleotide polymorphisms (SNPs) of
      the AURKA gene (rs1047972, rs2273535, rs2064836, and rs6024836) and HCC
      susceptibility as well as clinical outcomes in 312 patients with HCC and in 624
      cancer-free controls. We found that carriers of the TT allele of the variant
      rs1047972 were at greater risk of HCC compared with wild-type (CC) carriers.
      Moreover, carriers of at least one A allele in rs2273535 were less likely to
      progress to stage III/IV disease, develop large tumors or be classified into
      Child-Pugh class B or C. Individuals with at least one G allele at AURKA SNP
      rs2064863 were at lower risk of developing large tumors or progressing to Child
      Pugh grade B or C. Our results indicate that genetic variations in the AURKA gene
      may serve as an important predictor of early-stage HCC and be a reliable
      biomarker for the development of HCC.

PMID- 29333102
TI  - An Amino Acids Mixture Attenuates Glycemic Impairment but not Affects Adiposity
      Development in Rats Fed with AGEs-containing Diet.
AB  - Background: Unhealthy western dietary patterns lead to over-consumption of fat
      and advanced glycation end-products (AGEs), and these account for the
      developments of obesity, diabetes, and related metabolic disorders. Certain amino
      acids (AAs) have been recently demonstrated to improve glycemia and reduce
      adiposity. Therefore, our primary aims were to examine whether feeding an
      isoleucine-enriched AA mixture (4.5% AAs; Ile: 3.0%, Leu: 1.0%, Val: 0.2%, Arg:
      0.3% in the drinking water) would affect adiposity development and prevent the
      impairments of glycemic control in rats fed with the fat/AGE-containing diet
      (FAD). Methods: Twenty-four male Sprague-Dawley rats were assigned into 1)
      control diet (CD, N = 8), 2) FAD diet (FAD, N = 8), and 3) FAD diet plus AA
      (FAD/AA, N = 8). After 9-weeks intervention, the glycemic control capacity
      (glucose level, ITT, and HbA1c levels), body composition, and spontaneous
      locomotor activity (SLA) were evaluated, and the fasting blood samples were
      collected for analyzing metabolic related hormones (insulin, leptin, adiponectin,
      and corticosterone). The adipose tissues were also surgically collected and
      weighed. Results: FAD rats showed significant increases in weight gain, body fat
      %, blood glucose, HbA1c, leptin, and area under the curve of glucose during
      insulin tolerance test (ITT-glucose-AUC) in compared with the CD rats. However,
      the fasting levels of blood glucose, HbA1c, leptin, and ITT-glucose-AUC did not
      differ between CD and FAD/AA rats. FAD/AA rats also showed a greater increase in
      serum testosterone. Conclusion: The amino acid mixture consisting of Ile, Leu,
      Val, and Arg showed clear protective benefits on preventing the FAD-induced
      obesity and impaired glycemic control.

PMID- 29333103
TI  - Interleukin-35 Level Is Elevated in Patients with Chronic Hepatitis B Virus
      Infection.
AB  - Backgrounds: As one of the major public health problems, the hepatitis B virus
      (HBV) infection would activate the immune system. The outcome of HBV infection
      was affect significantly by the interactions between HBV and host immune
      response. Interleukins play important role in anti-viral immunity. Here we
      investigated the role of interleukin-35 (IL-35) in chronic HBV infection
      patients. Methods/Results: Serum IL-35 in 72 chronic hepatitis B virus infection
      patients and 41 healthy control subjects were analyzed by ELISA assay. The mRNA
      level of IL-35 in PBMCs was determined by RT-qPCR. In this study, we found that
      both protein and mRNA levels of IL-35 were significantly decreased in chronic HBV
      patients compared to the healthy controls. Furthermore, the statistical analysis
      found that serum IL-35 was significantly associated with HBV DNA (P =0.0158), ALT
      (P =0.0003), AST (P =0.0216), TB (P =0.0270) and AFP (P =0.0369). Importantly,
      correlation analysis also found that serum IL-35 level was negatively correlated
      with HBV DNA copies, ALT, AST, TB and AFP. Meanwhile, IL-35 treatment inhibited
      the level of HBV DNA, HBsAg and HBeAg in HepAD38 cells. Conclusion: Our study
      identified that IL-35 may be a novel marker associated with HBV infection and
      hepatocytes injury. These data suggested the potential use of IL-35 in the HBV
      treatment.

PMID- 29333104
TI  - What Did You Expect?: The Interaction Between Cigarette and Blunt vs. Non-Blunt
      Marijuana Use among African American Young Adults.
AB  - Background: Marijuana and tobacco co-use is highly prevalent among African
      American young adults. In an effort to inform prevention and treatment
      interventions, the current study examined the expectancies around the co-use of
      marijuana and cigarettes among African American young adults. Methods: An
      anonymous online survey recruited African American adults (N = 111) age 18 to 29
      who reported past-month marijuana and cigarette co-use. Participants completed
      the 14-item Nicotine and Marijuana Interaction Expectancy (NAMIE) Questionnaire,
      with three scales: (1) marijuana use increases tobacco use and urges, (2) tobacco
      use increases marijuana use and urges and (3) smoking to cope with marijuana
      urges. Participants also answered questions about marijuana and tobacco
      initiation and use. Analyses were conducted separately for blunt co-users (i.e.,
      blunt and cigarette use) and non-blunt co-users (i.e., non-blunt marijuana and
      cigarette use). Results: A majority of co-users (66%) used blunts as a form of co
      use. Non-blunt co-users had higher expectancy scores on NAMIE scales 2 and 3 than
      blunt co-users. However, only blunt co-users showed a positive association
      between severity of marijuana use and NAMIE scales 2 (p <.01) and 3 (p <.01).
      Conclusions: Findings provide further evidence for the use of the NAMIE and
      suggest a need to assess and address expectations regarding marijuana and tobacco
      co-use in prevention and treatment interventions, especially among young African
      American adults who co-use blunts and cigarettes.

PMID- 29333106
TI  - Which Point-of-Care Tests Would Be Most Beneficial to Add to Clinical Practice?:
      Findings From a Survey of 3 Family Medicine Clinics in the United States.
AB  - Background: Point-of-care tests (POCTs) are increasingly used in family medicine
      to facilitate screening, diagnosis, monitoring, treatment, and referral decisions
      for a variety of conditions. Point-of-care tests that clinicians believe might be
      beneficial to add to clinical practice and the conditions for which they would be
      most useful in family medicine remain poorly understood in the United States.
      Methods: Forty-two clinicians at 3 family medicine residency clinics completed a
      brief survey asking which POCTs they believed would be beneficial to add to their
      clinical practice and the conditions POCTs would be most useful for. We
      calculated frequencies of reported POCTs and conditions using descriptive
      statistics. Results: Clinicians identified 34 POCTs that would be beneficial to
      add to family medicine, of which hemoglobin A1c, chemistry panels, and human
      immunodeficiency virus and gonococcal and/or chlamydia were most frequently
      reported and anticipated would be used weekly. Clinicians reported 30 conditions
      for which they considered POCTs would be useful. Diabetes mellitus, sexually
      transmitted infections, and respiratory tract infections were the most often
      reported and were identified as benefiting diagnosis, monitoring, and treatment
      decisions. Conclusions: Clinicians identified a number of POCTs they viewed as
      being beneficial to add to their routine clinical practice, mostly to inform
      diagnosis and treatment planning. Some POCTs identified are available in the
      United States; thus, understanding barriers to implementation of these POCTs in
      primary care settings is necessary to optimize adoption.

PMID- 29333107
TI  - Cryptography Standards in Quantum Time: New wine in old wineskin?

PMID- 29333105
TI  - Measures and Metrics for Feasibility of Proof-of-Concept Studies With Human
      Immunodeficiency Virus Rapid Point-of-Care Technologies: The Evidence and the
      Framework.
AB  - Objective: Pilot (feasibility) studies form a vast majority of diagnostic studies
      with point-of-care technologies but often lack use of clear measures/metrics and
      a consistent framework for reporting and evaluation. To fill this gap, we
      systematically reviewed data to (a) catalog feasibility measures/metrics and (b)
      propose a framework. Methods: For the period January 2000 to March 2014, 2
      reviewers searched 4 databases (MEDLINE, EMBASE, CINAHL, Scopus), retrieved 1441
      citations, and abstracted data from 81 studies. We observed 2 major categories of
      measures, that is, implementation centered and patient centered, and 4
      subcategories of measures, that is, feasibility, acceptability, preference, and
      patient experience. We defined and delineated metrics and measures for a
      feasibility framework. We documented impact measures for a comparison. Findings:
      We observed heterogeneity in reporting of metrics as well as misclassification
      and misuse of metrics within measures. Although we observed poorly defined
      measures and metrics for feasibility, preference, and patient experience, in
      contrast, acceptability measure was the best defined. For example, within
      feasibility, metrics such as consent, completion, new infection, linkage rates,
      and turnaround times were misclassified and reported. Similarly, patient
      experience was variously reported as test convenience, comfort, pain, and/or
      satisfaction. In contrast, within impact measures, all the metrics were well
      documented, thus serving as a good baseline comparator. With our framework, we
      classified, delineated, and defined quantitative measures and metrics for
      feasibility. Conclusions: Our framework, with its defined measures/metrics, could
      reduce misclassification and improve the overall quality of reporting for
      monitoring and evaluation of rapid point-of-care technology strategies and their
      context-driven optimization.

PMID- 29333108
TI  - Bipolar Disorder in Primary Care: Integrated Care Experiences.
AB  - Primary care clinics are increasingly implementing collaborative care models to
      care for patients with psychiatric illnesses in primary care. The evidence base
      for the effectiveness of collaborative care has largely been derived from the
      care of patients with depression or anxiety disorders, although psychiatrists
      working in primary care may encounter patients with illnesses other than
      depression or anxiety disorder, notably bipolar disorder. Patients with bipolar
      disorder report having received treatment in primary care in equal proportions as
      those in specialty care settings over the past 12 months, although quality of
      care is lower in primary care than in specialty care settings. For patients
      already presenting to primary care, collaborative care is one population-based
      care model that may increase the proportion of individuals with bipolar disorder
      who are exposed to high-quality psychiatric care, such as appropriate medication
      treatment and laboratory monitoring. The primary care setting may even present
      unexpected strengths in caring for patients with bipolar disorder. Solutions to
      barriers to expanding the scope of collaborative care to include patients with
      bipolar disorder may apply to the care of patients with other complex disorders
      in the primary care setting.

PMID- 29333109
TI  - Ultrasonographic Findings of Renal Cell Carcinomas Associated with Xp11.2
      Translocation/TFE3 Gene Fusion.
AB  - Objective: This study was to investigate the features of renal carcinomas
      associated with Xp11.2 translocations/TFE3 gene fusions (Xp11.2-RCC) on
      conventional ultrasound (US) and contrast-enhanced ultrasound (CEUS). Methods: US
      and CEUS features of twenty-two cases with histopathologically proven Xp11.2-RCC
      were retrospectively reviewed. Results: 22 patients (11 males, 11 females) were
      included in this study, with a mean age of 28.3 +/- 20.4 years. Eight tumors
      (36.3%, 8/22) were in left kidney, and 14 tumors (63.7%, 14/22) were in right
      kidney. All tumors (100%, 22/22) were mixed echogenicity type. 13 tumors (59.1%,
      13/22) presented small dotted calcifications. The boundary of 14 tumors (63.6%,
      14/22) was sharp and the other 8 tumors' (36.4%, 8/22) boundary was blurry. By
      CEUS, in early phase, the solid element of all tumors showed obvious enhancement.
      In delayed phase, 13 tumors showed hypoenhancement, seven tumors showed
      isoenhancement, and 2 tumors showed hyperenhancement. There were irregular
      nonenhancement areas in all tumors inside. Conclusions: By US and CEUS, when
      children and adolescents were found to have hyperechoic mixed tumor in kidney
      with sharp margin and calcification, and the tumors showed obvious enhancement
      and hypoenhancement with irregular nonenhancement areas in the tumor in early
      phase and delayed phase, respectively, Xp11.2-RCC should be suspected.

PMID- 29333110
TI  - F-18 FP-CIT PET in Multiple System Atrophy of the Cerebellar Type: Additional
      Role in Treatment.
AB  - We evaluated the difference in the status of dopamine transporters (DATs)
      depending on Parkinsonism, cerebellar, and autonomic features using F-18 FP-CIT
      positron emission tomography (PET) in multiple system atrophy with cerebellar
      ataxia (MSA-C). We also assessed whether the DAT PET could be useful in the
      management of MSA-C. Forty-nine patients who were clinically diagnosed as
      possible to probable MSA-C were included. Based on the F-18 FP-CIT PET results,
      patients were classified into normal (n = 25) and abnormal (n = 24) scan groups.
      There were statistically significant differences in rigidity, bradykinesia,
      postural instability, asymmetry, and specific uptake ratio (SUR) between the two
      groups but no significant differences in tremor and cerebellar/autonomic
      symptoms. Dopaminergic medications were administered to 22 patients. All seven
      patients with normal scans showed no change, while 10 of the 15 patients with
      abnormal scans showed clinical improvement. There was a trend of a negative
      correlation between levodopa equivalent dose and SUR, but it was not
      statistically significant. DAT imaging, such as F-18 FP-CIT PET, may be useful in
      predicting the response to dopaminergic medication regardless of
      cerebellar/autonomic symptoms in MSA-C. In addition to being used for the
      diagnosis of the disease, it may be used as a treatment decision index.

PMID- 29333112
TI  - Integrating Occupational Therapy Specific Assessments in Practice: Exploring
      Practitioner Experiences.
AB  - Background: Occupational therapists sometimes find it challenging to integrate
      client-centered and occupational therapy specific assessments in practice. The
      aim of this study was to explore the use of occupational therapy specific
      assessments such as the Assessment of Motor and Process Skills (AMPS) among
      occupational therapists in Sweden and Japan. Methods: Interviews and qualitative
      thematic analyses were utilized. Findings: Four themes are reported: (1) use it
      or lose it, (2) simply no space until after hours, (3) biggest barriers can be
      colleagues, and (4) being more specific: communication. Conclusion: In keeping
      with previous studies, occupational therapists often find it challenging to
      implement client-centered and occupation-based assessment tools into practice.
      However, more work is needed to understand how best practices can be incorporated
      into a changing occupational therapy daily practice.

PMID- 29333113
TI  - Grating Oriented Line-Wise Filtration (GOLF) for Dual-Energy X-ray CT.
AB  - In medical X-ray Computed Tomography (CT), the use of two distinct X-ray source
      spectra (energies) allows dose-reduction and material discrimination relative to
      that achieved with only one source spectrum. Existing dual-energy CT methods
      include source kVp-switching, double-layer detection, dual-source gantry, and two
      pass scanning. Each method suffers either from strong spectral correlation or
      patient-motion artifacts. To simultaneously address these problems, we propose to
      improve CT data acquisition with the Grating Oriented Line-wise Filtration (GOLF)
      method, a novel X-ray filter that is placed between the source and patient. GOLF
      uses a combination of absorption and filtering gratings that are moved relative
      to each other and in synchronization with the X-ray tube kVp-switching process
      and/or the detector view-sampling process. Simulation results show that GOLF can
      improve the spectral performance of kVp-switching to match that of dual-source CT
      while avoiding patient motion artifacts and dual imaging chains. Although
      significant flux is absorbed by this pre-patient filter, the proposed GOLF method
      is a novel path for cost-effectively extracting dual-energy or multi-energy data
      and reducing radiation dose with or without kVp switching.

PMID- 29333111
TI  - Diet, Gut Microbiota, and Colorectal Cancer Prevention: A Review of Potential
      Mechanisms and Promising Targets for Future Research.
AB  - Diet plays an important role in the development of colorectal cancer. Emerging
      data have implicated the gut microbiota in colorectal cancer. Diet is a major
      determinant for the gut microbial structure and function. Therefore, it has been
      hypothesized that alterations in gut microbes and their metabolites may
      contribute to the influence of diet on the development of colorectal cancer. We
      review several major dietary factors that have been linked to gut microbiota and
      colorectal cancer, including major dietary patterns, fiber, red meat and sulfur,
      and obesity. Most of the epidemiologic evidence derives from cross-sectional or
      short-term, highly controlled feeding studies that are limited in size.
      Therefore, high-quality large-scale prospective studies with dietary data
      collected over the life course and comprehensive gut microbial composition and
      function assessed well prior to neoplastic occurrence are critically needed to
      identify microbiome-based interventions that may complement or optimize current
      diet-based strategies for colorectal cancer prevention and management.

PMID- 29333114
TI  - Carcinogenesis Induced by Low-dose Radiation.
AB  - Background: Although the effects of high dose radiation on human cells and
      tissues are relatively well defined, there is no consensus regarding the effects
      of low and very low radiation doses on the organism. Ionizing radiation has been
      shown to induce gene mutations and chromosome aberrations which are known to be
      involved in the process of carcinogenesis. The induction of secondary cancers is
      a challenging long-term side effect in oncologic patients treated with radiation.
      Medical sources of radiation like intensity modulated radiotherapy used in cancer
      treatment and computed tomography used in diagnostics, deliver very low doses of
      radiation to large volumes of healthy tissue, which might contribute to increased
      cancer rates in long surviving patients and in the general population. Research
      shows that because of the phenomena characteristic for low dose radiation the
      risk of cancer induction from exposure of healthy tissues to low dose radiation
      can be greater than the risk calculated from linear no-threshold model.
      Epidemiological data collected from radiation workers and atomic bomb survivors
      confirms that exposure to low dose radiation can contribute to increased cancer
      risk and also that the risk might correlate with the age at exposure.
      Conclusions: Understanding the molecular mechanisms of response to low dose
      radiation is crucial for the proper evaluation of risks and benefits that stem
      from these exposures and should be considered in the radiotherapy treatment
      planning and in determining the allowed occupational exposures.

PMID- 29333115
TI  - Clinical Significance of Fluorine-18-fluorodeoxyglucose Positron Emission
      Tomography/computed Tomography in the Follow-up of Colorectal Cancer: Searching
      off Approaches Increasing Specificity for Detection of Recurrence.
AB  - Background: Nearly 40% of colorectal cancer (CRC) recurs within 2 years after
      resection of primary tumor. Imaging with fluorine-18-fluorodeoxyglucose (l8F-FDG)
      positron emission tomography/computed tomography (PET/CT) is the most recent
      modality and often applied for the evaluation of metastatic spread during the
      follow-up period. Our goal was to study the diagnostic importance of 18F-FDG
      PET/CT data of maximum standardized uptake value (SUVmax), total lesion
      glycolysis (TLG) and the difference of SUVmax on dual-time imaging in CRC.
      Patients and methods: We examined the SUVmax value of lesions on control or
      restaging 18F-FDG-PET/CT of 53 CRC patients. All lesions with increased SUVmax
      values were confirmed by colonoscopy or histopathology. We compared PET/CT
      results with conventional imaging modalities (CT, MRI) and tumor markers
      (carbohydrate antigen 19-9 [Ca 19-9], carcinoembryonic antigen [CEA]). Results:
      Mean SUVmax was 6.9 +/- 5.6 in benign group, 12.7 +/- 6.1 in malignant group.
      Mean TLG values of malignant group and benign group were 401 and 148,
      respectively. 18F-FDG-PET/CT was truely positive in 48% of patients with normal
      Ca 19-9 or CEA levels and truely negative in 10% of cases with elevated Ca 19-9
      or CEA. CT or MRI detected suspicious malignancy in 32% of the patients and 18F
      FDG-PET/CT was truely negative in 35% of these cases. We found the most important
      and striking statistical difference of TLG value between the groups with benign
      and recurrent disease. Conclusions: Although SUVmax is a strong metabolic
      parameter (p = 0.008), TLG seems to be the best predictor in recurrence of CRC (p
      = 0.001); both are increasing the specificity of 18F-FDG-PET/CT.

PMID- 29333116
TI  - Is there a Role for Contrast-enhanced Ultrasound in the Detection and Biopsy of
      MRI Only Visible Breast Lesions?
AB  - Background: This study aimed to evaluate the feasibility of contrast-enhanced
      ultrasound (CEUS) and CEUS-guided interventions in the diagnostics of MRI visible
      targeted US occult breast lesions. Patients and methods: This retrospective study
      examined 10 females with 10 occult, MRI only detected breast lesions between July
      2014 and April 2017. Targeted second look US followed by CEUS with 2.4 ml of
      SonoVue(r) were performed for all of the lesions. After positive CEUS
      localization the same dose was repeated for confirmation and CEUS-guided
      interventions were performed. Results: MRI revealed 8 mass lesions with a mean
      size of 9 mm (range 5-16 mm) and 2 non-mass enhancing lesions of 10 and 20 mm in
      largest diameters. Targeted US revealed no morphological correlate for the
      lesions. Five out of 10 lesions (50%) were visible on CEUS. CEUS-guided core
      biopsy was performed on 4 lesions and 1 was marked with a clip for later surgical
      removal. Histopathological analysis confirmed 4 of them to be malignant. Three
      out of 5 nonvisible lesions on CEUS underwent MRI-guided interventions, 1 lesion
      was scheduled for follow-up as it was non-amenable for MRI biopsy, and 1 lesion
      was biopsied under US-guidance. Three of these nonvisible lesions on CEUS were
      confirmed to be malignant. Conclusions: Based on our preliminary results, CEUS is
      a feasible tool for detecting many MRI only visible breast lesions, resulting in
      a more cost effective and less time-consuming practice. It is a more convenient
      alternative than MRI guided biopsy and has the potential to be included in the
      diagnostic algorithm which evaluates MRI only visible breast lesions.

PMID- 29333117
TI  - Baseline Tumor Lipiodol Uptake after Transarterial Chemoembolization for
      Hepatocellular Carcinoma: Identification of a Threshold Value Predicting Tumor
      Recurrence.
AB  - Background: The aim of the study was to evaluate the association between baseline
      Lipiodol uptake in hepatocellular carcinoma (HCC) after transarterial
      chemoembolization (TACE) with early tumor recurrence, and to identify a threshold
      baseline uptake value predicting tumor response. Patients and methods: A single
      institution retrospective database of HCC treated with Lipiodol-TACE was
      reviewed. Forty-six tumors in 30 patients treated with a Lipiodol-chemotherapy
      emulsion and no additional particle embolization were included. Baseline Lipiodol
      uptake was measured as the mean Hounsfield units (HU) on a CT within one week
      after TACE. Washout rate was calculated dividing the difference in HU between the
      baseline CT and follow-up CT by time (HU/month). Cox proportional hazard models
      were used to correlate baseline Lipiodol uptake and other variables with tumor
      response. A receiver operating characteristic (ROC) curve was used to identify
      the optimal threshold for baseline Lipiodol uptake predicting tumor response.
      Results: During the follow-up period (mean 5.6 months), 19 (41.3%) tumors
      recurred (mean time to recurrence = 3.6 months). In a multivariate model, low
      baseline Lipiodol uptake and higher washout rate were significant predictors of
      early tumor recurrence (P = 0.001 and < 0.0001, respectively). On ROC analysis, a
      threshold Lipiodol uptake of 270.2 HU was significantly associated with tumor
      response (95% sensitivity, 93% specificity). Conclusions: Baseline Lipiodol
      uptake and washout rate on follow-up were independent predictors of early tumor
      recurrence. A threshold value of baseline Lipiodol uptake > 270.2 HU was highly
      sensitive and specific for tumor response. These findings may prove useful for
      determining subsequent treatment strategies after Lipiodol TACE.

PMID- 29333118
TI  - The Relationship between Chondromalacia Patella, Medial Meniscal Tear and Medial
      Periarticular Bursitis in Patients with Osteoarthritis.
AB  - Background: This study investigated the presence of bursitis in the medial
      compartment of the knee (pes anserine, semimembranosus-tibial collateral
      ligament, and medial collateral ligament bursa) in osteoarthritis, chondromalacia
      patella and medial meniscal tears. Patients and methods: Radiological findings of
      100 patients undergoing magnetic resonance imaging with a preliminary diagnosis
      of knee pain were retrospectively evaluated by two radiologists. The first
      radiologist assessed all patients in terms of osteoarthritis, chondromalacia
      patella and medial meniscal tear. The second radiologist was blinded to these
      results and assessed the presence of bursitis in all patients. Results: Mild
      osteoarthritis (grade I and II) was determined in 55 patients and severe
      osteoarthritis (grade III and IV) in 45 cases. At retropatellar cartilage
      evaluation, 25 patients were assessed as normal, while 29 patients were diagnosed
      with mild chondromalacia patella (grade I and II) and 46 with severe
      chondromalacia patella (grade III and IV). Medial meniscus tear was determined in
      51 patients. Severe osteoarthritis and chondromalacia patella were positively
      correlated with meniscal tear (p < 0.001 and p = 0.018, respectively).
      Significant correlation was observed between medial meniscal tear and bursitis in
      the medial compartment (p = 0.038). Presence of medial periarticular bursitis was
      positively correlated with severity of osteoarthritis but exhibited no
      correlation with chondromalacia patella (p = 0.023 and p = 0.479, respectively).
      Evaluation of lateral compartment bursae revealed lateral collateral ligament
      bursitis in 2 patients and iliotibial bursitis in 5 patients. Conclusions: We
      observed a greater prevalence of bursitis in the medial compartment of the knee
      in patients with severe osteoarthritis and medial meniscus tear.

PMID- 29333119
TI  - Phytotherapeutics Oridonin and Ponicidin show Additive Effects Combined with
      Irradiation in Pancreatic Cancer in Vitro.
AB  - Background: Chemoradiation of locally advanced non-metastatic pancreatic cancer
      can lead to secondary operability by tumor mass reduction. Here, we analyzed
      radiomodulating effects of oridonin and ponicidin in pancreatic cancer in vitro.
      Both agents are ent-kaurane diterpenoids, extracted from Isodon rubescens, a
      plant that is well known in Traditional Chinese Medicine. Cytotoxic effects have
      recently been shown in different tumor entities for both agents. Materials and
      methods: Pancreatic cancer cell lines AsPC-1, BxPC-3, Panc-1 and MIA PaCa-2 were
      pretreated with oridonin or ponicidin and irradiated with 2 Gy to 6 Gy. Long-term
      survival was determined by clonogenic assay. Cell cycle effects and intensity of
      gammaH2AX as indicator for DNA double-strand breaks were investigated by flow
      cytometry. Western blotting was used to study the DNA double-strand break repair
      proteins Ku70, Ku80 and XRCC4. Results: Oridonin and ponicidin lead to a dose
      dependent reduction of clonogenic survival and an increase in gammaH2AX. Combined
      with irradiation we observed additive effects and a prolonged G2/M-arrest. No
      relevant changes in the levels of the DNA double-strand break repair proteins
      were detected. Conclusions: Pretreatment with oridonin or ponicidin followed by
      irradiation lead to an additional reduction in survival of pancreatic cancer
      cells in vitro, presumably explained by an induced prolonged G2/M-arrest. Both
      agents seem to induce DNA double-strand breaks but do not interact with the non
      homologous end joining (NHEJ) pathway.

PMID- 29333120
TI  - Focused Transhepatic Electroporation Mediated by Hypersaline Infusion through the
      Portal Vein in Rat Model. Preliminary Results on Differential Conductivity.
AB  - Background: Spread hepatic tumours are not suitable for treatment either by
      surgery or conventional ablation methods. The aim of this study was to evaluate
      feasibility and safety of selectively increasing the healthy hepatic conductivity
      by the hypersaline infusion (HI) through the portal vein. We hypothesize this
      will allow simultaneous safe treatment of all nodules by irreversible
      electroporation (IRE) when applied in a transhepatic fashion. Material and
      methods: Sprague Dawley (Group A, n = 10) and Athymic rats with implanted hepatic
      tumour (Group B, n = 8) were employed. HI was performed (NaCl 20%, 3.8 mL/Kg) by
      trans-splenic puncture. Deionized serum (40 mL/Kg) and furosemide (2 mL/Kg) were
      simultaneously infused through the jugular vein to compensate hypernatremia.
      Changes in conductivity were monitored in the hepatic and tumour tissue. The
      period in which hepatic conductivity was higher than tumour conductivity was
      defined as the therapeutic window (TW). Animals were monitored during 1-month
      follow-up. The animals were sacrificed and selective samples were used for
      histological analysis. Results: The overall survival rate was 82.4% after the HI
      protocol. The mean maximum hepatic conductivity after HI was 2.7 and 3.5 times
      higher than the baseline value, in group A and B, respectively. The mean maximum
      hepatic conductivity after HI was 1.4 times higher than tumour tissue in group B
      creating a TW to implement selective IRE. Conclusions: HI through the portal vein
      is safe when the hypersaline overload is compensated with deionized serum and it
      may provide a TW for focused IRE treatment on tumour nodules.

PMID- 29333121
TI  - Minimally Invasive Electrochemotherapy Procedure for Treating Nasal Duct Tumors
      in Dogs using a Single Needle Electrode.
AB  - Background: Nasal cavity tumors are usually diagnosed late, when they already
      have infiltrated adjacent tissues thus requiring very aggressive treatments with
      serious side effects. Here we use electrochemotherapy (ECT), a well demonstrated
      treatment modality for superficial tumors. Materials and methods: In the case of
      deep-seated tumors, the main limitation of ECT is reaching the tumor with an
      appropriate electric field. To overcome this limitation we introduce the single
      needle electrode (SiNE), a minimally invasive device that can deliver an
      appropriate electric field with a simple procedure. Twenty-one canine patients
      with spontaneous tumors were selected, eleven were treated using the SiNE with
      ECT, and ten with surgery plus adjuvant chemotherapy as a control group. Results:
      In the SiNE group, 27% achieved a complete response, 64% had a partial response,
      and 9% had a stable disease. This means that 91% of objective responses were
      obtained. The mean overall survival was 16.86 months (4-32 months, median 16.5
      months), with a survival rate significantly higher (p = 0.0008) when compared
      with control group. The only side effect observed was the inflammation of the
      treated nasal passage, which was controlled with corticosteroid therapy for one
      week. One year after the treatment, 60% of the canine of the SiNE group vs. 10%
      of the control group remained alive, and after the 32 months follow-up, the
      survival rate were 30% and 0%, respectively. Conclusions: ECT with the SiNE can
      be safely used in canine to treat nasal tumors with encouraging results.

PMID- 29333122
TI  - Metformin Enhanced in Vitro Radiosensitivity Associates with G2/M Cell Cycle
      Arrest and Elevated Adenosine-5'-monophosphate-activated Protein Kinase Levels in
      Glioblastoma.
AB  - Background: It is hypothesized that metabolism plays a strong role in cancer cell
      regulation. We have recently demonstrated improved progression-free survival in
      patients with glioblastoma who received metformin as an antidiabetic substance
      during chemoradiation. Although metformin is well-established in clinical use the
      influence of metformin in glioblastoma is far from being understood especially in
      combination with other treatment modalities such as radiation and temozolomide.
      Materials and Methods: In this study, we examined the influence of metformin in
      combinations with radiation and temozolomide on cell survival (clonogenic
      survival), cell cycle (routine flow cytometric analysis, FACScan), and
      phosphorylated Adenosine-5'-monophosphate-activated protein kinase (AMPK) (Phopho
      AMPKalpha1 - ELISA) levels in glioblastoma cell lines LN18 and LN229. Results:
      Metformin and temozolomide enhanced the effectiveness of photon irradiation in
      glioblastoma cells. Cell toxicity was more pronounced in O6-methylguanine DNA
      methyltransferase (MGMT) promoter non-methylated LN18 cells. Induction of a G2/M
      phase cell cycle block through metformin and combined treatments was observed up
      to 72 h. These findings were associated with elevated levels of activated AMPK
      levels in LN229 cells but not in LN18 cells after irradiation, metformin, and
      temozolomide treatment. Conclusions: Radiosensitizing effects of metformin on
      glioblastoma cells treated with irradiation and temozolomide in vitro coincided
      with G2/M arrest and changes in pAMPK levels.

PMID- 29333123
TI  - Evaluation of Deformable Image Registration (DIR) Methods for Dose Accumulation
      in Nasopharyngeal Cancer Patients during Radiotherapy.
AB  - Introduction: Deformable image registration (DIR) is used to modify structures
      according to anatomical changes for observing the dosimetric effect. In this
      study, megavoltage computed tomography (MVCT) images were used to generate
      cumulative doses for nasopharyngeal cancer (NPC) patients by various DIR methods.
      The performance of the multiple DIR methods was analysed, and the impact of dose
      accumulation was assessed. Patients and methods: The study consisted of five NPC
      patients treated with a helical tomotherapy unit. The weekly MVCT images at the
      1st, 6th, 11th, 16th, 21st, 26th, and 31st fractions were used to assess the dose
      accumulation by the four DIR methods. The cumulative dose deviations from the
      initial treatment plan were analysed, and correlations of these variations with
      the anatomic changes and DIR methods were explored. Results: The target dose
      received a slightly different result from the initial plan at the end of the
      treatment. The organ dose differences increased as the treatment progressed to
      6.8% (range: 2.2 to 10.9%), 15.2% (range: -1.7 to 36.3%), and 6.4% (range: -1.6
      to 13.2%) for the right parotid, the left parotid, and the spinal cord,
      respectively. The mean uncertainty values to estimate the accumulated doses for
      all the DIR methods were 0.21 +/- 0.11 Gy (target dose), 1.99 +/- 0.76 Gy (right
      parotid), 1.19 +/- 0.24 Gy (left parotid), and 0.41 +/- 0.04 Gy (spinal cord).
      Conclusions: Accuracy of the DIR methods affects the estimation of dose
      accumulation on both the target dose and the organ dose. The DIR methods provide
      an adequate dose estimation technique for observation as a result of inter
      fractional anatomic changes and are beneficial for adaptive treatment strategies.

PMID- 29333124
TI  - Long Term Results of Radiotherapy in Vulvar Cancer Patients in Slovenia between
      1997-2004.
AB  - Background: The aim of this retrospective single institution study was to analyse
      long term results of vulvar cancer treatment with conventional 2D radiotherapy in
      Slovenia between years 1997-2004. Patients and methods: Fifty-six patients,
      median age 74.4 years +/- 9.7 years, mainly stage T2 or T3, were included in the
      study. All patients were treated with radiotherapy, which was combined with
      surgery (group A), used as the primary treatment (group B) or at the time of
      relapse (group C). Chemotherapy was added in some patients. Histology, grade,
      lymph node status, details of surgery, radiation dose to the primary tumour,
      inguinofemoral and pelvic area as well as local control (LC) and survival were
      evaluated. Results: Overall survival (OS), disease specific survival (DSS) and LC
      rates at 10-years for all patients were as follows: 22.7%, 34.5% and 41.1%,
      respectively. The best 10-years results of the treatment were achieved in the
      primary operated patients treated with adjuvant radiotherapy +/-chemotherapy (OS
      31.9%, DSS 40.6% and LC 47.6%). Positive lymph nodes had a strong influence on
      LC. In case of positive nodes LC decreased by 60% (p = 0.03) and survival
      decreased by 50% (p = 0.2). There was a trend to a better LC with higher doses >=
      54.0 Gy (p = 0.05). Conclusions: The best treatment option for patients with
      advanced vulvar cancer is combined treatment with surgery and radiotherapy +/-
      chemotherapy, if feasible. Radiotherapy with the dose of >= 54.0 Gy should be
      considered to achieve better LC if positive adverse factors are present.

PMID- 29333125
TI  - Association between SLC19A1 Gene Polymorphism and High Dose Methotrexate Toxicity
      in Childhood Acute Lymphoblastic Leukaemia and Non Hodgkin Malignant Lymphoma:
      Introducing a Haplotype based Approach.
AB  - Background: We investigated the clinical relevance of SLC 19A1 genetic
      variability for high dose methotrexate (HD-MTX) related toxicities in children
      and adolescents with acute lymphoblastic leukaemia (ALL) and non Hodgkin
      malignant lymphoma (NHML). Patients and methods: Eighty-eight children and
      adolescents with ALL/NHML were investigated for the influence of SLC 19A1 single
      nucleotide polymorphisms (SNPs) and haplotypes on HD-MTX induced toxicities.
      Results: Patients with rs2838958 TT genotype had higher probability for mucositis
      development as compared to carriers of at least one rs2838958 C allele (OR 0.226
      (0.071-0.725), p < 0.009). Haplotype TGTTCCG (H4) statistically significantly
      reduced the risk for the occurrence of adverse events during treatment with HD
      MTX (OR 0.143 (0.023-0.852), p = 0.030). Conclusions: SLC 19A1 SNP and haplotype
      analysis could provide additional information in a personalized HD-MTX therapy
      for children with ALL/NHML in order to achieve better treatment outcome. However
      further studies are needed to validate the results.

PMID- 29333126
TI  - Impact on Radiation Dose and Volume V57 Gy of the Brain on Recurrence and
      Survival of Patients with Glioblastoma Multiformae.
AB  - Background: The aim of the study was to analyze impact of irradiated brain volume
      V57 Gy (volume receiving 57 Gy and more) on time to progression and survival of
      patients with glioblastoma. Patients and methods: Dosimetric analysis of
      treatment plan data has been performed on 70 patients with glioblastoma, treated
      with postoperative radiochemotherapy with temozolomide, followed by adjuvant
      temozolomide. Patients were treated with 2 different methods of definition of
      treatment volumes and prescription of radiation dose. First group of patients has
      been treated with one treatment volume receiving 60 Gy in 2 Gy daily fraction (31
      patients) and second group of the patients has been treated with "cone-down"
      technique, which consisted of two phases of treatment: the first phase of 46 Gy
      in 2 Gy fraction followed by "cone-down" boost of 14 Gy in 2 Gy fraction (39
      patients). Quantification of V57 Gy and ratio brain volume/V57Gy has been done.
      Average values of both parameters have been taken as a threshold value and
      patients have been split into 2 groups for each parameter (values smaller/ lager
      than threshold value). Results: Mean value for V57 Gy was 593.39 cm3 (range
      166.94 to 968.60 cm3), mean value of brain volume has was 1332.86 cm3 (range
      1047.00 to 1671.90 cm3) and mean value of brain-to-V57Gy ratio was 2.46 (range
      1.42 to 7.67). There was no significant difference between two groups for both
      V57 Gy and ratio between brain volume and V57 Gy. Conclusions: Irradiated volume
      with dose 57 Gy or more (V57 Gy) and ration between whole brain volume and 57 Gy
      had no impact on time to progression and survival of patients with glioblastoma.

PMID- 29333127
TI  - Quality Assurance Procedures based on Dosimetric, Gamma Analysis as a Fast
      Reliable Tool for Commissioning Brachytherapy Treatment Planning Systems.
AB  - Background: Fast and easily repeatable methods for commissioning procedures for
      brachytherapy (BT) treatment planning systems (TPS) are needed. Radiochromic film
      dosimetry with gamma analysis is widely used in external beam quality assurance
      (QA) procedures and planar film dosimetry is also increasingly used for
      verification of the dose distribution in BT applications. Using the gamma
      analysis method for comparing calculated and measured dose data could be used for
      commissioning procedures of the newly developed TG-186 and MBDCA calculation
      algorithms. The aim of this study was dosimetric verification of the calculation
      algorithm used in TPS when the CT/MRI ring applicator is used. Materials and
      methods: Ring applicators with 26 and 30 mm diameters and a 60 mm intra-uterine
      tube with 60 degrees  angle were used for verification. Gafchromic(r) EBT films
      were used as dosimetric media. Dose grids, corresponding to each plane
      (dosimetric film location), were exported from the TPS as a raw data.
      Gafchromic(r) films were digitized after irradiation. gamma analysis of the data
      were performed using the OMNI Pro I'mRT(r) system, as recommended by the AAPM TG
      119 rapport criterion for gamma analysis of 3%, 3 mm and a level of 95%. Results:
      For the 26 mm and 30 mm rings, the average gamma ranged, respectively, from 0.1
      to 0.44 and from 0.1 to 0.27. In both cases, 99% of the measured points
      corresponded with the calculated data. Conclusions: This analysis showed
      excellent agreement between the dose distribution calculated with the TPS and the
      doses measured by Gafchromic films. This finding confirms the viability of using
      film dosimetry in BT.

PMID- 29333128
TI  - In vitro transfection of anti-tumor miR-101 induces BIM, a pro-apoptotic protein,
      expression in acute myeloid leukemia (AML).
AB  - Acute myeloid leukemia (AML) frequently relapses after initial treatment, though
      it is possible that drug resistance occurs. Hence, it seems necessary to develop
      novel therapies such as gene therapy specifically via miRNA transfection.
      MicroRNA-101 has been considered as a tumor suppressor in different types of
      cancer. It is demonstrated that exogenous miR-101 transfection is associated with
      decreased viability in AML in this paper. Besides, the increase of pro-apoptotic
      protein BIM expression in both mRNA and protein level has been illustrated. The
      recent findings provide an insight into the novel function of miR-101 in AML by
      activating BIM as an important mediator in intrinsic apoptosis pathways.
      Generally, miR-101 has been considered as a therapeutic target in our data and
      might have a valuable role in AML.

PMID- 29333129
TI  - The predictive value of pre- and post-induction chemotherapy plasma EBV DNA level
      and tumor volume for the radiosensitivity of locally advanced nasopharyngeal
      carcinoma.
AB  - This study was dedicated to investigate the predictive value of pre- and post
      induction chemotherapy plasma EBV (Epstein-Barr Virus) DNA level and tumor volume
      for the radiosensitivity of locally advanced NPC. 129 previously untreated
      locally advanced NPC patients were enrolled. Plasma EBV-DNA copy number and tumor
      volume was detected before and after induction chemotherapy. The tumor volume was
      also measured after radiotherapy. Among 129 patients, 98 were positive for EBV
      DNA. The residual gross target volume of the primary tumor (GTVnx) and GTVnd
      after radiotherapy was positively correlated with post-induction chemotherapy EBV
      copy number (rho=0.357, P<0.001; rho=0.356, P<0.001, respectively). Univariate
      logistic regression analyses showed that the AUC of ROC curves of post-induction
      chemotherapy tumor volume, tumor regression rate before and after induction
      chemotherapy, post-induction EBV copy number, EBV decrease rate for predicting no
      residual nasopharyngeal tumor were 0.859, 0.782, 0.678 and 0.657, respectively.
      Multivariate logistic analyses showed that T stage, post-induction chemotherapy
      EBV copy number and tumor volume were independent predictors for no residual
      nasopharyngeal tumor after radiotherapy. The changes in plasma EBV DNA and tumor
      volume during treatment could be used to predict the sensitivity of locally
      advanced NPC patients in response to intensity-modulated radiation therapy
      (IMRT).

PMID- 29333130
TI  - An in silico approach in predicting the possible mechanism involving restoration
      of wild-type p53 functions by small molecular weight compounds in tumor cells
      expressing R273H mutant p53.
AB  - R273H mutant p53 is a DNA-contact mutant that renders p53 dysfunctional due to a
      single substitution of Arg273 for His273. Rescuing R273 mutant p53 implies that a
      competent molecule would have to bind to the site of DNA-contact hot spots to
      complement the loss of contact with the DNA-binding domain. Here, curcumin,
      flavokawain B, and alpinetin were docked against the crystal structure of R273H
      mutant p53 in silico. Consequently, all the compounds bind to the cavity of R273H
      mutant p53 with a dissociation constant estimated to have 36.57, 70.77, and 75.11
      uM for curcumin, flavokawain B, and alpinetin, respectively. Subsequently, each
      molecule was able to bind to the R273H mutant p53 by interacting with the DNA
      contact hot spot Arg248 and mutant R273H, thereby compensating for the loss of
      direct contact with the DNA-binding domain. Furthermore, all the molecules were
      able to induce a direct contact with the consensus site of the DNA binding
      domain, thus maintaining DNA-contact residues with the DNA. The present findings
      offer preliminary indirect supporting evidence that small molecular weight
      compounds may certainly rescue DNA-contact mutant p53, which may lay a foundation
      for designing a competent and effective molecule capable of rescuing mutant p53
      in tumor cells expressing R273H mutant p53.

PMID- 29333131
TI  - miR-494 protects pancreatic beta-cell function by targeting PTEN in gestational
      diabetes mellitus.
AB  - Gestational diabetes mellitus (GDM) is one of the most common pregnancy
      complications characterized by insulin resistance and pancreatic beta-cell
      dysfunction. Increasing evidence suggests that microRNAs (miRNAs) play key roles
      in the diverse types of diabetes, including GDM. However, the underlying
      mechanisms remain largely unknown. The purpose of this study is to investigate
      the role of microRNAs in GDM. The microarray data of dysregulated miRNAs in blood
      and placenta was retrieved in the GEO dataset under the accession number
      GSE19649. Quantitative reverse transcription PCR (qRT-PCR) was performed to
      analyze the expression levels of miR-494 in peripheral blood from twenty pairs of
      gestational diabetes (GDM) women and healthy women. Then, we investigated the
      effects of miR-494 on the insulin secretion of pancreatic beta-cells. Moreover,
      the role of this miR-494 in regulating the proliferation and apoptosis of
      pancreatic beta-cells were determined by MTT assay and flow cytometry,
      respectively in INS1 cells transfected with a miR-494 mimic or inhibitor. In
      addition, the direct target of miR-494 was confirmed using 3' untranslated region
      (UTR) luciferase reporter assay. Our data demonstrated that the miR-494 level was
      significantly decreased in the blood of GDM patients, and the low level was
      associated with a high concentration of blood glucose. Furthermore,
      overexpression of miR-494 improved pancreatic beta-cell dysfunction by enhancing
      insulin secretion and total insulin content, inducing cell proliferation, and
      inhibiting cell apoptosis, whereas miR-494 knockdown exhibited decreased insulin
      secretion and proliferation, as well as stimulated apoptosis. In addition,
      phosphatase and tensin homolog (PTEN) which has been shown to play a pivotal role
      in apoptosis, was proved to be a direct target of miR-494 in pancreatic beta
      cells. More importantly, siRNA-induced downregulation of PTEN reversed the
      effects of miR-494 knockdown on insulin secretion, cell proliferation, and
      apoptosis of pancreatic beta-cells.

PMID- 29333132
TI  - Detection of aflatoxin-producing fungi isolated from Nile tilapia and fish feed.
AB  - Contamination of fish by fungi and their mycotoxins poses major health concerns
      to human and animals. Therefore, our study was aimed to investigate Aspergillus
      flavus (A. flavus) infections and the levels of aflatoxins in Nile tilapia,
      Oreochromis niloticus (O. niloticus), and fish feed. Samples from O. niloticus
      and fish feed (n=25 for each) were randomly collected from private fish farms at
      Qena province, Egypt, during the winter season. Different Aspergillus spp. were
      detected in 60 % and 64 % of O. niloticus and fish feed, respectively. HPLC-based
      analysis revealed aflatoxin-producing activity in 75 % and 83 % of A. flavus
      isolates from fish and fish feed, respectively. While 96 % of O. niloticus
      muscles and fish feed samples were contaminated with aflatoxins, the detected
      levels were below the permissible limits, i.e. 20 ug/kg. Moreover, experimental
      infection with toxicogenic A. flavus isolates was conducted to evaluate their
      pathogenicity in O. niloticus. Expectedly, experimental infections of O.
      niloticus with A. flavus were associated with several clinical symptoms reported
      in naturally infected fish, e.g. yellow coloration with skin ulceration,
      hemorrhagic ulcerative patches on gills and skin, corneal opacity, fin rot and
      abdominal distention. Furthermore, aflatoxicogenic A. flavus isolates from fish
      were sensitive to herbal clove oil. Even though the measured levels of aflatoxin
      were below permissible limits, effort should be placed on further reduction of
      exposure to genotoxic and carcinogenic mycotoxins.

PMID- 29333133
TI  - Highlight report: Occupational urinary bladder cancer.

PMID- 29333134
TI  - Highlight report: The pseudolobule in liver fibrosis.

PMID- 29333135
TI  - Highlight report: Metabolomics in hepatotoxicity testing.

PMID- 29333136
TI  - Highlight report: The relationship of DNA copy number alterations and mRNA levels
      in cancer.

PMID- 29333137
TI  - Highlight report: Intratumoral metabolomic heterogeneity of breast cancer.

PMID- 29333138
TI  - Highlight report: Monitoring cytochrome P450 activities in living hepatocytes.

PMID- 29333140
TI  - Farewell Message from the Editor-in-Chief.

PMID- 29333139
TI  - A framework for an alternatives assessment dashboard for evaluating chemical
      alternatives applied to flame retardants for electronic applications.
AB  - The goal of alternatives assessment (AA) is to facilitate a comparison of
      alternatives to a chemical of concern, resulting in the identification of safer
      alternatives. A two stage methodology for comparing chemical alternatives was
      developed. In the first stage, alternatives are compared using a variety of human
      health effects, ecotoxicity, and physicochemical properties. Hazard profiles are
      completed using a variety of online sources and quantitative structure activity
      relationship models. In the second stage, alternatives are evaluated utilizing an
      exposure/risk assessment over the entire life cycle. Exposure values are
      calculated using screening-level near-field and far-field exposure models. The
      second stage allows one to more accurately compare potential exposure to each
      alternative and consider additional factors that may not be obvious from separate
      binned persistence, bioaccumulation, and toxicity scores. The methodology was
      utilized to compare phosphate-based alternatives for decabromodiphenyl ether
      (decaBDE) in electronics applications.

PMID- 29333141
TI  - Foreword of the Editor.

PMID- 29333142
TI  - IFCC Task Force on Chronic Kidney Disease (Integrated Project) - (TF-CKD) Special
      Issue.

PMID- 29333143
TI  - Task Force on CKD - We have Come a Long Way.
AB  - Chronic Kidney Disease (CKD) is an important medical condition where diagnosis,
      staging and monitoring is largely based on routine laboratory tests. During the
      last 15 years there have been many important changes in the clinical management
      of CKD described in key international guidelines. In order to successfully
      implement these guidelines, laboratories must collaborate with clinicians to
      provide a co-ordinated service, including accurate measurements and of creatinine
      and urine albumin and reporting of an estimated glomerular filtration rate
      (eGFR). The IFCC/WASPaLM Task Force on Chronic Kidney Disease (TF-CKD) was
      established in 2008 and since that time has worked to improve laboratory testing
      in CKD. Key aspects of the work of the TF-CKD include supporting national
      laboratory medicine organisations to develop CKD testing guidelines, recognition
      of the vital role of collaboration between laboratory and clinical organisations,
      the importance of accurate measurements, and endorsement of the KDIGO 2012 CKD
      guidelines. A key function of the TF-CKD has been to facilitate sharing and
      learning between countries to provide the best outcomes.

PMID- 29333144
TI  - Did Creatinine Standardization Give Benefits to the Evaluation of Glomerular
      Filtration Rate?
AB  - During the last decade, a lot of efforts has been made to improve the evaluation
      of renal functions. Measured Glomerular Filtration Rate (GFR) remains the only
      valuable test to confirm or confute the status of chronic kidney disease (CKD)
      and is recommended by Kidney Disease Global Outcomes guidelines when estimation
      of GFR is not reliable. However, in routine clinical practice, serum creatinine
      remains the one of the most prescribed biological parameters and is an undeniable
      factor, alone or in association with other parameters, of the estimation of GFR.
      Since many years, a great improvement in the creatinine measurements was realized
      because of the standardization of the methods and fabrication of an international
      standard with concentration near to physiological ones (SRM967). Standardization
      according to Isotopic Dilution Mass Spectrometry dramatically improves the
      analytical performances of creatinine assays resulting in a more accurate
      estimation of GFR using creatinine based equations. Indeed, the standardization
      of creatinine improves the analytical performance by reducing the bias and
      removing the influence of the interfering substances. However, biological
      variability of creatinine is not affected by analytical standardization and
      remains a limitation to the use of creatinine in some selected populations,
      having extreme ages or weights like children, elderly subjects, obese or
      malnourished populations. Standardization of creatinine assays result in a clear
      improvement of estimated GFR in general population but alternative methods should
      be used when creatinine production or metabolism is impaired.

PMID- 29333145
TI  - Moving Toward Standardization of Urine Albumin Measurements.
AB  - Measurement of urine albumin is important for detecting and monitoring kidney
      disease. At the present time, measurement of urine albumin is not standardized
      due to the lack of a reference system, which includes both a reference
      measurement procedure and certified reference materials. Developing a reference
      system will provide a means for clinical laboratory measurement procedures to
      become standardized and will enable successful use of uniform clinical decision
      points. Currently, urine albumin results vary in excess of 40% depending on which
      commercially available measurement procedure is utilized for measurement.
      Clinicians may struggle with classification of kidney disease in part due to
      differences in measurements from lack of agreement among laboratory methodologies
      employed when assessing urine albumin concentrations. This report focuses on
      current findings in urine albumin testing, highlights important measurement and
      reporting considerations, and presents strategies for developing a reference
      measurement procedure to enable standardization of urine albumin measurements.

PMID- 29333146
TI  - Cystatin C is Indispensable for Evaluation of Kidney Disease.
AB  - The present minireview of the place of cystatin C in clinical medicine
      emphasizes, and discuss the evidence, that cystatin C-based GFR-estimating
      equations do not require the use of vague terms like race and sex, that cystatin
      C-based GFR-esti mating equations are useful for both children and adults,
      including the elderly, that the best GFR-estimation requires simultaneous use of
      both cystatin C- and creatinine-based equations, that cystatin C-based GFR
      estimating equations are superior to creatinine-based equations in predicting end
      stage renal disease, cardiovascular manifestations, hospitalisation and death,
      and, finally that cystatin C is required to diagnose the new syndrome "Shrunken
      Pore Syndrome" with its high mortality and morbidity, even in the absence of
      reduced GFR. When automated laboratory equipment is available, the cost of
      cystatin C is comparable to that of enzymatically determined creatinine. The
      conclusion is that cystatin C should be used at least as often as creatinine in
      clinical medicine.

PMID- 29333147
TI  - Novel Filtration Markers for GFR Estimation.
AB  - Creatinine-based glomerular filtration rate estimation (eGFRcr) has been improved
      and refined since the 1970s through both the Modification of Diet in Renal
      Disease (MDRD) Study equation in 1999 and the CKD Epidemiology Collaboration (CKD
      EPI) equation in 2009, with current clinical practice dependent primarily on eGFR
      for accurate assessment of GFR. However, researchers and clinicians have
      recognized limitations of relying on creatinine as the only filtration marker,
      which can lead to inaccurate GFR estimates in certain populations due to the
      influence of non-GFR determinants of serum or plasma creatinine. Therefore,
      recent literature has proposed incorporation of multiple serum or plasma
      filtration markers into GFR estimation to improve precision and accuracy and
      decrease the impact of non-GFR determinants for any individual biomarker. To this
      end, the CKD-EPI combined creatinine-cystatin C equation (eGFRcr-cys) was
      developed in 2012 and demonstrated superior accuracy to equations relying on
      creatinine or cystatin C alone (eGFRcr or eGFRcys). Now, the focus has broadened
      to include additional novel filtration markers to further refine and improve GFR
      estimation. Beta-2-microglobulin (B2M) and beta-trace-protein (BTP) are two
      filtration markers with established assays that have been proposed as candidates
      for improving both GFR estimation and risk prediction. GFR estimating equations
      based on B2M and BTP have been developed and validated, with the CKD-EPI combined
      BTP-B2M equation (eGFRBTP-B2M) demonstrating similar performance to eGFR and
      eGFR. Additionally, several studies have demonstrated that both B2M and BTP are
      associated with outcomes in CKD patients, including cardiovascular events, ESRD
      and mortality. This review will primarily focus on these two biomarkers, and will
      highlight efforts to identify additional candidate biomarkers through
      metabolomics-based approaches.

PMID- 29333149
TI  - A Summary of Worldwide National Activities in Chronic Kidney Disease (CKD)
      Testing.
AB  - Chronic kidney disease (CKD) is a major public health issue worldwide and is
      associated with adverse health outcomes, especially in low- and middle-income
      countries. In a cash limited healthcare system, guidelines that improve the
      efficiency of health care free up resources needed for other healthcare services.
      This short review presents some examples from national acitivities in CKD
      testing, including countries throughout the globe: Mexico in North America,
      Uruguay in South America, Italy in Europe, Nigeria in Africa and India in Asia.
      Considering the fact that treatment of CKD is cost-effective and improves
      outcomes, this observation argue in favor of including CKD in national guidelines
      and noncommunicable chronic disease (NCD) programs. This diverse example of
      national activities fullfil the very first step in achieving this goal.

PMID- 29333148
TI  - A Pathway to National Guidelines for Laboratory Diagnostics of Chronic Kidney
      Disease - Examples from Diverse European Countries.
AB  - The principal benefit of guidelines is to improve the quality of care received by
      patients. In the 2012 Clinical Practice Guideline for the Evaluation and
      Management of Chronic Kidney Disease (KDIGO) was released and it is designed to
      provide information and assist decision making. This review gives a brief
      overview of a various national CKD guidelines that rely on the newly released
      KDIGO guidelines. All of the included countries (France, Turkey, Norway and
      Croatia) are non-English speaking countries and they differ in population and
      socio economic aspects. Examples shown in this review may provide valuable
      experience for countries that are in process of creating their national CKD
      guidelines.

PMID- 29333150
TI  - Evaluation of the Correlation Coefficient of Polyethylene Glycol Treated and
      Direct Prolactin Results and Comparability with Different Assay System Results.
AB  - : The presence of Macro prolactin is a significant cause of elevated prolactin
      resulting in misdiagnosis in all automated systems. Poly ethylene glycol (PEG)
      pretreatment is the preventive process but such process includes the probability
      of loss of a fraction of bioactive prolactin. Surprisingly, PEG treated EQAS &
      IQAS samples in Cobas e 411 are found out to be correlating with direct results
      of at least 3 immunoassay systems and treated and untreated Cobas e 411 results
      are comparable by a correlation coefficient. Comparison of EQAS, IQAS and patient
      samples were done to find out the trueness of such correlation factor. Study with
      patient's results have established the correlation coefficient is valid for very
      small concentration of prolactin also. Materials and methods: EQAS, IQAS and 150
      patient samples were treated with PEG and prolactin results of treated and
      untreated samples obtained from Roche Cobas e 411. 25 patient's results (treated)
      were compared with direct results in Advia Centaur, Architect I & Access2
      systems. Statistical calculations: Correlation coefficient was obtained from
      trend line of the treated and untreated results. Two tailed p-value obtained from
      regression coefficient(r) and sample size. Results and discussion: The
      correlation coefficient is in the range (0.761-0.771). Reverse correlation range
      is (1.289-1.301). r value of two sets of calculated results were 0.995. Two
      tailed p- value is zero approving dismissal of null hypothesis. Conclusion: The z
      score of EQAS does not always assure authenticity of resultsPEG precipitation is
      correlated by the factor 0.761 even in very small
      concentrationsAbbreviationsGFCgel filtration chromatographyPEGpolyethylene
      glycolEQASexternal quality assurance systemM-PRLmacro
      prolactinPRLprolactinECLIAelectro-chemiluminescence immunoassayCLIAclinical
      laboratory improvement amendmentsIQASinternal quality assurance systemrregression
      coefficient.

PMID- 29333151
TI  - Lab Test Findings in the Elderly.

PMID- 29333152
TI  - Erratum: (1) Pediatric Obesity and Cardiometabolic Disorders: Risk Factors and
      Biomarkers.
AB  - [This corrects the article on p. 6 in vol. 28, PMID: 28439216.].

PMID- 29333153
TI  - PPAR-gamma Agonists and Their Role in Primary Cicatricial Alopecia.
AB  - Peroxisome proliferator-activated receptor gamma (PPAR-gamma) is a ligand
      activated nuclear receptor that regulates the transcription of various genes.
      PPAR-gamma plays roles in lipid homeostasis, sebocyte maturation, and peroxisome
      biogenesis and has shown anti-inflammatory effects. PPAR-gamma is highly
      expressed in human sebaceous glands. Disruption of PPAR-gamma is believed to be
      one of the mechanisms of primary cicatricial alopecia (PCA) pathogenesis, causing
      pilosebaceous dysfunction leading to follicular inflammation. In this review
      article, we discuss the pathogenesis of PCA with a focus on PPAR-gamma
      involvement in pathogenesis of lichen planopilaris (LPP), the most common
      lymphocytic form of PCA. We also discuss clinical trials utilizing PPAR-agonists
      in PCA treatment.

PMID- 29333154
TI  - Whole-Exome Sequencing-Based Mutational Profiling of Hepatitis B Virus-Related
      Early-Stage Hepatocellular Carcinoma.
AB  - Background: Hepatocellular carcinoma (HCC) ranks as the third leading cause of
      cancer-related mortality in China with increasing incidence. This study is
      designed to explore early genetic changes implicated in HCC tumorigenesis and
      progression by whole-exome sequencing. Methods: We firstly sequenced the whole
      exomes of 5 paired hepatitis B virus-related early-stage HCC and peripheral blood
      samples, followed by gene ontological analysis and pathway analysis of the single
      nucleotide variants discovered. Then, the mutations of high frequency were
      further confirmed by Sanger sequencing. Results: We identified a mutational
      signature of dominant T:A>A:T transversion in early HCC and significantly
      enriched pathways including ECM-receptor interaction, axon guidance, and focal
      adhesion and enriched biological processes containing cell adhesion, axon
      guidance, and regulation of pH. Eight genes, including MUC16, UNC79, USH2A,
      DNAH17, PTPN13, TENM4, PCLO, and PDE1C, were frequently mutated. Conclusions:
      This study reveals a mutational profile and a distinct mutation signature of
      T:A>A:T transversion in early-stage HCC with HBV infection, which will enrich our
      understanding of genetic characteristics of the early-stage HCC.

PMID- 29333155
TI  - Genetic Polymorphisms: A Novel Perspective on Acute Pancreatitis.
AB  - Acute pancreatitis (AP) is a complex disease that results in significant
      morbidity and mortality. For many decades, it has compelled researchers to
      explore the exact pathogenesis and the understanding of the pathogenesis of AP
      has progressed dramatically. Currently, premature trypsinogen activation and NF
      kappaB activation for inflammation are two remarkable hypotheses for the
      mechanism of AP. Meanwhile, understanding of the influence of genetic
      polymorphisms has resulted in tremendous development in the understanding of the
      advancement of complex diseases. Now, genetic polymorphisms of AP have been noted
      gradually and many researchers devote themselves to this emerging area. In this
      review, we comprehensively describe genetic polymorphisms combined with the
      latest hypothesis of pathogenesis associated with AP.

PMID- 29333156
TI  - Intravenous Magnesium Sulphate for Analgesia after Caesarean Section: A
      Systematic Review.
AB  - Objective: To summarise the evidence for use of intravenous magnesium for
      analgesic effect in caesarean section patients. Background: Postcaesarean pain
      requires effective analgesia. Magnesium, an N-methyl-D-aspartate receptor
      antagonist and calcium-channel blocker, has previously been investigated for its
      analgesic properties. Methods: A systematic search was conducted of PubMed,
      Scopus, MEDLINE, Cochrane Library, and Google Scholar databases for randomised
      control trials comparing intravenous magnesium to placebo with analgesic outcomes
      in caesarean patients. Results: Ten trials met inclusion criteria. Seven were
      qualitatively compared after exclusion of three for unclear bias risk. Four
      trials were conducted with general anaesthesia, while three utilised neuraxial
      anaesthesia. Five of seven trials resulted in decreased analgesic requirement
      postoperatively and four of seven resulted in lower serial visual analogue scale
      scores. Conclusions: Adjunct analgesic agents are utilised to improve analgesic
      outcomes and minimise opioid side effects. Preoperative intravenous magnesium may
      decrease total postcaesarean rescue analgesia consumption with few side effects;
      however, small sample size and heterogeneity of methodology in included trials
      restricts the ability to draw strong conclusions. Therefore, given the apparent
      safety and efficacy of magnesium, its role as an adjunct analgesic in caesarean
      section patients should be further investigated with the most current anaesthetic
      techniques.

PMID- 29333157
TI  - Potential Developmental and Reproductive Impacts of Triclocarban: A Scoping
      Review.
AB  - Triclocarban (TCC) is an antimicrobial agent used in personal care products.
      Although frequently studied with another antimicrobial, triclosan, it is not as
      well researched, and there are very few reviews of the biological activity of
      TCC. TCC has been shown to be a possible endocrine disruptor, acting by enhancing
      the activity of endogenous hormones. TCC has been banned in the US for certain
      applications; however, many human populations, in and outside the US, exhibit
      exposure to TCC. Because of the concern of the health effects of TCC, we
      conducted a scoping review in order to map the current body of literature on the
      endocrine, reproductive, and developmental effects of TCC. The aim of this
      scoping review was to identify possible endpoints for future systematic review
      and to make recommendations for future research. A search of the literature until
      August 2017 yielded 32 relevant studies in humans, rodents, fish, invertebrates,
      and in vitro. Based on the robustness of the literature in all three evidence
      streams (human, animal, and in vitro), we identified three endpoints for possible
      systematic review: estrogenic activity, androgenic activity, and offspring
      growth. In this review, we describe the body of evidence and make recommendations
      for future research.

PMID- 29333158
TI  - Testosterone: Relationships with Metabolic Disorders in Men-An Observational
      Study from SPECT-China.
AB  - Background: The strength of associations between total testosterone (TT) and
      metabolic parameters may vary in different nature of population structure;
      however, no study has ever given this information in Chinese population,
      especially those without metabolic syndrome (MS). We aimed to analyze the
      association magnitudes between TT and multiple metabolic parameters in general
      Chinese men. Methods: 4309 men were recruited from SPECT-China study in 2014
      2015, which was performed in 22 sites in East China. TT, weight status, and
      various metabolic parameters were measured. Linear and logistic regressions were
      used to analyze the associations. Results: Men in lower TT quartiles had worse
      metabolic parameters including body mass index, triglycerides, HbA1c, and HOMA-IR
      (all P for trend < 0.001). Body mass index (B -0.32, 95%CI -0.35 to -0.29) and
      obesity (OR 0.40, 95%CI 0.35-0.45) had the largest association magnitude per one
      SD increment in TT, while blood pressure and hypertension (OR 0.90, 95%CI 0.84
      0.98) had the smallest. These associations also persisted in individuals without
      metabolic syndrome. Conclusions: Obesity indices had closer relationships with TT
      than most other metabolic measures with blood pressure the least close. These
      associations remained robust after adjustment for adiposity and in subjects
      without metabolic syndrome.

PMID- 29333159
TI  - Ultrasound-Guided Percutaneous Microwave Ablation for Solid Benign Thyroid
      Nodules: Comparison of MWA versus Control Group.
AB  - Background: The aim of this research is to investigate the feasibility of
      percutaneous ultrasound-guided microwave ablation (MWA) for benign solid thyroid
      nodules. Methods: Ultrasound-guided percutaneous microwave ablation was performed
      for 90 benign solid thyroid nodules in 75 patients. The volume changes of the
      nodules were evaluated before and after microwave ablation, and the cosmetic
      grading and clinical symptoms were assessed as well. Results: The volume of all
      the 90 benign thyroid nodules obviously decreased after microwave ablation at 3-,
      6-, 9-, and 12-month follow-ups (p < 0.01), while that of the control group
      increased at the follow-up of 12 months (p < 0.01). The volume reduction rate
      (VRR) at 3-, 6-, 9-, and 12-month follow-ups was 55.98%, 69.31%, 76.65%, and
      84.67% in the MWA group, respectively. The cosmetic problems and clinical
      symptoms were also improved in the MWA group. All the patients are well tolerated
      to the procedure. Hoarseness occurred in 2 cases (2.7%) and Horner syndrome in 1
      case (1.3%), and 1 patient (1.3%) developed slight burn on cervical skin.
      Conclusions: Ultrasound-guided percutaneous microwave ablation is a practical
      method for treating benign solid thyroid nodules, and the complications were
      acceptable. The trial is registered with clinicaltrials.gov with the registration
      number NCT03057925.

PMID- 29333160
TI  - Corrigendum to "The Current Practice of Screening, Prevention, and Treatment of
      Androgen-Deprivation-Therapy Induced Osteoporosis in Patients with Prostate
      Cancer".
AB  - [This corrects the article DOI: 10.1155/2012/958596.].

PMID- 29333161
TI  - Robustness of Tomato Quality Evaluation Using a Portable Vis-SWNIRS for Dry
      Matter and Colour.
AB  - The utility of a handheld visible-short wave near infrared spectrophotometer
      utilising an interactance optical geometry was assessed in context of the
      noninvasive determination of intact tomato dry matter content, as an index of
      final ripe soluble solids content, and colouration, as an index of maturation to
      guide a decision to harvest. Partial least squares regression model robustness
      was demonstrated through the use of populations of different harvest dates or
      growing conditions for calibration and prediction. Dry matter predictions of
      independent populations of fruit achieved R2 ranging from 0.86 to 0.92 and bias
      from -0.14 to 0.03%. For a CIE a* colour model, prediction R2 ranged from 0.85 to
      0.96 and bias from -1.18 to -0.08. Updating the calibration model with new
      samples to extend range in the attribute of interest and in sample matrix is key
      to better prediction performance. The handheld spectrometry system is recommended
      for practical implementation in tomato cultivation.

PMID- 29333162
TI  - A Multivariate Methodological Workflow for the Analysis of FTIR Chemical Mapping
      Applied on Historic Paint Stratigraphies.
AB  - In the field of applied researches in heritage science, the use of multivariate
      approach is still quite limited and often chemometric results obtained are often
      underinterpreted. Within this scenario, the present paper is aimed at
      disseminating the use of suitable multivariate methodologies and proposes a
      procedural workflow applied on a representative group of case studies, of
      considerable importance for conservation purposes, as a sort of guideline on the
      processing and on the interpretation of this FTIR data. Initially, principal
      component analysis (PCA) is performed and the score values are converted into
      chemical maps. Successively, the brushing approach is applied, demonstrating its
      usefulness for a deep understanding of the relationships between the multivariate
      map and PC score space, as well as for the identification of the spectral bands
      mainly involved in the definition of each area localised within the score maps.

PMID- 29333163
TI  - Infiltrating Cardiac Synovial Sarcoma Presenting as Acute Cerebrovascular
      Accident.
AB  - Primary cardiac sarcoma is a rare malignant myocardial neoplasm that does not
      exhibit gender predominance or age predilection. The classification of these
      tumors includes several subtypes, of which synovial sarcoma is a rare
      manifestation. When present, these tumors portend a poor prognosis with high
      morbidity and mortality that is attributable to their inherent infiltrative
      capacity, especially in the absence of treatment. The general consensus for
      treatment is surgical excision and neoadjuvant chemotherapy and radiotherapy. In
      this report, a case of synovial sarcoma involving the left ventricular outflow
      tract and aortic valve is presented.

PMID- 29333165
TI  - Adipose-Derived Stromal Cells for Treatment of Patients with Chronic Ischemic
      Heart Disease (MyStromalCell Trial): A Randomized Placebo-Controlled Study.
AB  - We aimed to evaluate the effect of intramyocardial injections of autologous VEGF
      A165-stimulated adipose-derived stromal cells (ASCs) in patients with refractory
      angina. MyStromalCell trial is a randomized double-blind placebo-controlled study
      including sixty patients with CCS/NYHA class II-III, left ventricular ejection
      fraction > 40%, and at least one significant coronary artery stenosis. Patients
      were treated with ASC or placebo in a 2 : 1 ratio. ASCs from the abdomen were
      culture expanded and stimulated with VEGF-A165. At 6 months follow-up, bicycle
      exercise tolerance increased significantly in time duration 22 s (95%CI -164 to
      208 s) (P = 0.034), in watt 4 (95%CI -33 to 41, 0.048), and in METs 0.2 (95%CI 
      1.4 to 1.8) (P = 0.048) in the ASC group while there was a nonsignificant
      increase in the placebo group in time duration 9 s (95%CI -203 to 221 s) (P =
      0.053), in watt 7 (95%CI -40 to 54) (P = 0.41), and in METs 0.1 (95%CI -1.7 to
      1.9) (P = 0.757). The difference between the groups was not significant (P =
      0.680, P = 0.608, and P = 0.720 for time duration, watt, and METs, resp.).
      Intramyocardial delivered VEGF-A165-stimulated ASC treatment was safe but did not
      improve exercise capacity compared to placebo. However, exercise capacity
      increased in the ASC but not in the placebo group. This trial is registered with
      ClinicalTrials.gov NCT01449032.

PMID- 29333164
TI  - When Long Noncoding RNAs Meet Genome Editing in Pluripotent Stem Cells.
AB  - Most of the human genome can be transcribed into RNAs, but only a minority of
      these regions produce protein-coding mRNAs whereas the remaining regions are
      transcribed into noncoding RNAs. Long noncoding RNAs (lncRNAs) were known for
      their influential regulatory roles in multiple biological processes such as
      imprinting, dosage compensation, transcriptional regulation, and splicing. The
      physiological functions of protein-coding genes have been extensively
      characterized through genome editing in pluripotent stem cells (PSCs) in the past
      30 years; however, the study of lncRNAs with genome editing technologies only
      came into attentions in recent years. Here, we summarize recent advancements in
      dissecting the roles of lncRNAs with genome editing technologies in PSCs and
      highlight potential genome editing tools useful for examining the functions of
      lncRNAs in PSCs.

PMID- 29333166
TI  - Influence of Different ECM-Like Hydrogels on Neurite Outgrowth Induced by Adipose
      Tissue-Derived Stem Cells.
AB  - Mesenchymal stem cells (MSCs) have been proposed for spinal cord injury (SCI)
      applications due to their capacity to secrete growth factors and vesicles
      secretome-that impacts important phenomena in SCI regeneration. To improve MSC
      survival into SCI sites, hydrogels have been used as transplantation vehicles.
      Herein, we hypothesized if different hydrogels could interact differently with
      adipose tissue-derived MSCs (ASCs). The efficacy of three natural hydrogels,
      gellan gum (functionalized with a fibronectin peptide), collagen, and a hydrogel
      rich in laminin epitopes (NVR-gel) in promoting neuritogenesis (alone and
      cocultured with ASCs), was evaluated in the present study. Their impact on ASC
      survival, metabolic activity, and gene expression was also evaluated. Our results
      indicated that all hydrogels supported ASC survival and viability, being this
      more evident for the functionalized GG hydrogels. Moreover, the presence of
      different ECM-derived biological cues within the hydrogels appears to differently
      affect the mRNA levels of growth factors involved in neuronal survival,
      differentiation, and axonal outgrowth. All the hydrogel-based systems supported
      axonal growth mediated by ASCs, but this effect was more robust in functionalized
      GG. The data herein presented highlights the importance of biological cues within
      hydrogel-based biomaterials as possible modulators of ASC secretome and its
      effects for SCI applications.

PMID- 29333167
TI  - Myocardial Regeneration via Progenitor Cell-Derived Exosomes.
AB  - In the past 20 years, a variety of cell products has been evaluated in terms of
      their capacity to treat patients with acute myocardial infarction and chronic
      heart failure. Despite initial enthusiasm, therapeutic efficacy has overall been
      disappointing, and clinical application is costly and complex. Recently, a subset
      of small extracellular vesicles (EVs), commonly referred to as "exosomes," was
      shown to confer cardioprotective and regenerative signals at a magnitude similar
      to that of their donor cells. The conceptual advantage is that they may be
      produced in industrial quantities and stored at the point-of-care for off-the
      shelf application, ideally without eliciting a relevant recipient immune response
      or other adverse effects associated with viable cells. The body of evidence on
      beneficial exosome-mediated effects in animal models of heart diseases is rapidly
      growing. However, there is significant heterogeneity in terms of exosome source
      cells, isolation process, therapeutic dosage, and delivery mode. This review
      summarizes the current state of research on exosomes as experimental therapy of
      heart diseases and seeks to identify roadblocks that need to be overcome prior to
      clinical application.

PMID- 29333169
TI  - The DEAD-Box RNA Helicase DDX3 Interacts with m6A RNA Demethylase ALKBH5.
AB  - DDX3 is a member of the family of DEAD-box RNA helicases. DDX3 is a multifaceted
      helicase and plays essential roles in key biological processes such as cell
      cycle, stress response, apoptosis, and RNA metabolism. In this study, we found
      that DDX3 interacted with ALKBH5, an m6A RNA demethylase. The ATP domain of DDX3
      and DSBH domain of ALKBH5 were indispensable to their interaction with each
      other. Furthermore, DDX3 could modulate the demethylation of mRNAs. We also
      showed that DDX3 regulated the methylation status of microRNAs and there was an
      interaction between DDX3 and AGO2. The dynamics of m6A RNA modification is still
      a field demanding further investigation, and here, we add a link by showing that
      RNA demethylation can be regulated by proteins such as DDX3.

PMID- 29333168
TI  - Mesenchymal Stem Cell Benefits Observed in Bone Marrow Failure and Acquired
      Aplastic Anemia.
AB  - Acquired aplastic anemia (AA) is a type of bone marrow failure (BMF) syndrome
      characterized by partial or total bone marrow (BM) destruction resulting in
      peripheral blood (PB) pancytopenia, which is the reduction in the number of red
      blood cells (RBC) and white blood cells (WBC), as well as platelets (PLT). The
      first-line treatment option of AA is given by hematopoietic stem cell (HSCs)
      transplant and/or immunosuppressive (IS) drug administration. Some patients did
      not respond to the treatment and remain pancytopenic following IS drugs. The
      studies are in progress to test the efficacy of adoptive cellular therapies as
      mesenchymal stem cells (MSCs), which confer low immunogenicity and are reliable
      allogeneic transplants in refractory severe aplastic anemia (SAA) cases.
      Moreover, bone marrow stromal cells (BMSC) constitute an essential component of
      the hematopoietic niche, responsible for stimulating and enhancing the
      proliferation of HSCs by secreting regulatory molecules and cytokines, providing
      stimulus to natural BM microenvironment for hematopoiesis. This review summarizes
      scientific evidences of the hematopoiesis improvements after MSC transplant,
      observed in acquired AA/BMF animal models as well as in patients with acquired
      AA. Additionally, we discuss the direct and indirect contribution of MSCs to the
      pathogenesis of acquired AA.

PMID- 29333170
TI  - Multiple Myeloma-Derived Exosomes Regulate the Functions of Mesenchymal Stem
      Cells Partially via Modulating miR-21 and miR-146a.
AB  - Exosomes derived from cancer cells can affect various functions of mesenchymal
      stem cells (MSCs) via conveying microRNAs (miRs). miR-21 and miR-146a have been
      demonstrated to regulate MSC proliferation and transformation. Interleukin-6 (IL
      6) secreted from transformed MSCs in turn favors the survival of multiple myeloma
      (MM) cells. However, the effects of MM exosomes on MSC functions remain largely
      unclear. In this study, we investigated the effects of OPM2 (a MM cell line)
      exosomes (OPM2-exo) on regulating the proliferation, cancer-associated fibroblast
      (CAF) transformation, and IL-6 secretion of MSCs and determined the role of miR
      21 and miR-146a in these effects. We found that OPM2-exo harbored high levels of
      miR-21 and miR-146a and that OPM2-exo coculture significantly increased MSC
      proliferation with upregulation of miR-21 and miR-146a. Moreover, OPM2-exo
      induced CAF transformation of MSCs, which was evidenced by increased fibroblast
      activated protein (FAP), alpha-smooth muscle actin (alpha-SMA), and stromal
      derived factor 1 (SDF-1) expressions and IL-6 secretion. Inhibition of miR-21 or
      miR-146a reduced these effects of OPM2-exo on MSCs. In conclusion, MM could
      promote the proliferation, CAF transformation, and IL-6 secretion of MSCs
      partially through regulating miR21 and miR146a.

PMID- 29333171
TI  - Exclusive Breastfeeding Practice and Associated Factors among Mothers Attending
      Private Pediatric and Child Clinics, Addis Ababa, Ethiopia: A Cross-Sectional
      Study.
AB  - Background: The prevalence of exclusive breastfeeding (EBF) is globally low (35%)
      in sub-Saharan Africa, whereas it is 58% in Ethiopia. Exclusive breastfeeding has
      the potential to prevent 11.6% of under-five deaths in developing countries.
      Therefore, the main objective of this study was to assess the exclusive
      breastfeeding practice and associated factors on mothers attending private
      pediatric and child clinics in Addis Ababa, Ethiopia. Methods: An institutional
      based cross-sectional study design was used. A total of 380 samples were
      obtained. Data were collected using a self-administered questionnaire. Data was
      entered and analyzed using SPSS version 16. Descriptive statistics and logistic
      regression analysis were used. Results: From 380 mothers, only 44.2% of the
      mothers practiced EBF. Two hundred (52.6%) mothers started breastfeeding within 1
      hour of delivery; 161 (42.4%) of the mothers gave extra food before six months,
      and 244 (64.2%) believed that exclusive breastfeeding was sufficient. Moreover,
      288 (75.8%) mothers breastfed their children eight or more times per day.
      Spontaneous vaginal delivery was a significant factor to practice EBF (AOR: 1.86,
      95% CI: 1.19-2.89). Conclusion: EBF practice in this study was low. Spontaneous
      vaginal delivery was a significant factor for EBF; hence, it is very crucial to
      promote EBF.

PMID- 29333172
TI  - Examining the Relationship between Park Neighborhoods, Features, Cleanliness, and
      Condition with Observed Weekday Park Usage and Physical Activity: A Case Study.
AB  - Background: Little research has comprehensively explored how park features,
      quality indicators, and neighborhood environments are associated with observed
      park usage and physical activity (PA). This case study examined whether weekday
      park usage and PA differ by neighborhood type, across numerous categories of park
      features, and according to park feature condition and cleanliness. Methods:
      Direct observation was used to capture the number of users and PA levels within
      143 park features in 6 parks (3 urban, 3 suburban) over the course of six weeks.
      Audits of park environments assessed the type, condition, and cleanliness of all
      features and amenities. Results: Urban parks experienced greater usage, but a
      higher proportion of sedentary users than suburban parks. Usage and PA levels
      differed across types of park features, with splash pads, pools, paths, and play
      structures having the greatest proportion of active users. Usage did not differ
      by park feature condition and cleanliness, but greater condition and cleanliness
      were generally associated with higher PA levels. Conclusions: Factors such as
      neighborhood context, types of park features, and condition and cleanliness can
      impact park usage and PA levels and should be targets for researchers and
      planners aiming to foster more user-friendly and active neighborhood park
      environments.

PMID- 29333173
TI  - Prevalence and Perinatal Outcomes of Singleton Term Breech Delivery in Wolisso
      Hospital, Oromia Region, Southern Ethiopia: A Cross-Sectional Study.
AB  - Background: Breech deliveries have always been topical issues in obstetrics.
      Neonates undergoing term breech deliveries have long-term morbidity up to the
      school age irrespective of mode of delivery. Objective: To determine prevalence
      and perinatal outcomes of singleton term breech delivery. Methods: Hospital based
      cross-sectional study was conducted on 384 participants retrospectively.
      Descriptive and analytical statistics was used. Result: A total of 384 breech
      deliveries were included. Prevalence of singleton breech deliveries in the
      hospital was 3.4%. The perinatal outcome of breech deliveries was 322 (83.9%).
      Adverse perinatal outcome of singleton term breech delivery was significantly
      associated with women's age of greater than or equal to 35 years (AOR = 2.62, 95%
      CI = 1.14-6.03), fully dilated cervix (AOR = 0.48, 95% CI = 0.25-0.91), ruptured
      membrane (AOR = 5.11, 95% CI = 2.25-11.6), and fetal weight of <2500 g (AOR =
      6.77, 95% CI = 3.22-14.25). Conclusion: Entrapment of head, birth asphyxia, and
      cord prolapse were the most common causes of perinatal mortality. Factors like
      fetal weight <2500 gm, mothers of age 35 years and above, those mothers not
      having a fully dilated cervix, and mothers with ruptured membrane were associated
      with increased perinatal mortality.

PMID- 29333174
TI  - A quantitative framework for assessing ecological resilience.
AB  - Quantitative approaches to measure and assess resilience are needed to bridge
      gaps between science, policy and management. In this paper, we revisit
      definitions of resilience and suggest a quantitative framework for assessing
      ecological resilience sensu Holling (1973). Ecological resilience as an emergent
      ecosystem phenomenon can be decomposed into complementary attributes (scales,
      adaptive capacity, thresholds and alternative regimes) that embrace the
      complexity inherent to ecosystems. Quantifying these attributes simultaneously
      provides opportunities to move from the assessment of specific resilience within
      an ecosystem towards a broader measurement of its general resilience. We provide
      a framework, based on testable hypotheses, which allows assessment of
      complementary attributes of ecological resilience. By implementing the framework
      in adaptive approaches to management, inference and modeling, key uncertainties
      can be reduced incrementally over time and learning about the general resilience
      of dynamic ecosystems maximized. Such improvements are needed because uncertainty
      about global environmental change impacts and their effects on resilience is
      high. Improved resilience assessments will ultimately facilitate an optimized use
      of limited resources for management.

PMID- 29333175
TI  - East-West, Collectivist-Individualist: A Cross-Cultural Examination of
      Temperament in Toddlers from Chile, Poland, South Korea, and the U.S.
AB  - The present study examined toddler temperament across Chilean, South Korean,
      Polish, and US samples, providing an opportunity to examine both collectivist
      individualist and East-West contrasts. The effect of culture on the three factor
      and 18 dimension scores provided by the Early Childhood Behavior Questionnaire
      were investigated. Results provide evidence of cross-cultural differences between
      the four samples. Chilean toddlers scored significantly higher than US, Polish,
      and South Korean children on the overall factor of Negative Affectivity, as well
      as higher than the Polish and South Korean samples on the Surgency factor. South
      Korean toddlers scored significantly higher on the factor of Effortful Control,
      and two related dimensions, than US, Polish, or Chilean samples. Results are
      discussed in terms of the apparent roles of individualism/collectivism and East
      West distinctions in shaping temperament development.

PMID- 29333176
TI  - Reverse Engineering the Inflammatory "Clock": From Computational Modeling to
      Rational Resetting.
AB  - Properly-regulated inflammation is central to homeostasis. Traumatic injury,
      hemorrhagic shock, septic shock, and other injury-related processes such as wound
      healing are associated with dysregulated inflammation. Like many biological
      processes, inflammation is a dynamic, complex system whose function, like that of
      an analog clock, cannot be discerned simply from a laundry list of its parts
      (data). The advent of multiplexed platforms for gathering biological data, while
      providing an unprecedented level of detailed information about the inflammatory
      response, has paradoxically also proven to be overwhelming. This problem is
      especially acute when the datasets involve time courses, since typical
      statistical analyses and data-driven modeling are geared towards single time
      points. Various groups have addressed this problem using dynamic approaches to
      data-driven and mechanistic computational modeling. These modeling tools can be
      thought of as the "gears" and "hands" of the "clock," and have led to insights
      regarding principal drivers, dynamic networks, feedbacks, and regulatory switches
      that characterize and perhaps regulate the inflammatory response. In parallel,
      mechanistic computational models have given an abstracted sense of how the
      inflammatory "clock" works, leading to in silico models of critically ill
      individuals and populations. Integrating data-driven and mechanistic modeling may
      point the way to a rational "resetting" of inflammation via model-driven
      precision medicine.

PMID- 29333177
TI  - The Vasodilatory Effects of Anti-Inflammatory Herb Medications: A Comparison
      Study of Four Botanical Extracts.
AB  - Inflammation plays a pivotal role in the development and progression of
      cardiovascular diseases, in which, the endothelium dysfunction has been a key
      element. The current study was designed to explore the vasodilatory effect of
      anti-inflammatory herbs which have been traditionally used in different clinical
      applications. The total saponins from Actinidia arguta radix (SAA), total
      flavonoids from Glycyrrhizae radix et rhizoma (FGR), total coumarins from
      Peucedani radix (CPR), and total flavonoids from Spatholobi caulis (FSC) were
      extracted. The isometric measurement of vasoactivity was used to observe the
      effects of herbal elements on the isolated aortic rings with or without
      endothelium. To understand endothelium-independent vasodilation, the effects of
      herb elements on agonists-induced vasocontractility and on the contraction of
      endothelium-free aortic rings exposed to a Ca2+-free medium were examined.
      Furthermore, the role of nitric oxide signaling in endothelium-dependent
      vasodilation was also evaluated. In summary, FGR and FSC exhibit potent anti
      inflammatory effects compared to CPR and SAA. FGR exerts the strongest
      vasodilatory effect, while CPR shows the least. The relaxation induced by SAA and
      FSC required intact endothelia. The mechanism of this vasodilation might involve
      eNOS. CPR-mediated vasorelaxation appears to involve interference with
      intracellular calcium homeostasis, blocking Ca2+ influx or releasing
      intracellular Ca2+.

PMID- 29333178
TI  - Efficacy of Combined XingZhi-YiNao Granules and Hyperbaric Oxygen Therapy for
      Cognition and Motor Dysfunction in Patients with Delayed Encephalopathy after
      Acute Carbon Monoxide Poisoning.
AB  - Purpose: To investigate the efficacy of XingZhi-YiNao (XZYN) granules and
      hyperbaric oxygenation (HBO) for cognition and motor dysfunction in patients with
      delayed encephalopathy after acute carbon monoxide poisoning (DEACMP). Methods:
      Eighty-nine patients with DEACMP were randomly divided into control group (n =
      19), HBO group (n = 32), and XZYN group (n = 38). All patients received
      conventional treatment. HBO group received HBO therapy once daily. XZYN group
      received extra XZYN granules plus HBO treatment. The related indexes including
      activity of daily living (ADL) scale, Montreal cognitive assessment (MoCA) scale,
      and mini mental state examination (MMSE) scale were measured. Cerebral white
      matter injury, age related white matter changes (ARWMC) scale, and the amplitude
      and latency of P300 were assessed. Results: Compared with control group, the
      neurological function scores of ADL, MoCA, and MMSE in HBO and XZYN groups were
      significantly improved, the impairment degree of brain white matter and cognition
      function were obviously alleviated, the latencies of P300 were significantly
      shortened, and the amplitudes of P300 were evidently increased (P < 0.05).
      Treatment efficacy of XZYN group was superior to that of HBO group (P < 0.05).
      Conclusion: Combined XZYN granules and HBO can significantly improve cognition
      and motor functions in patients with DEACMP.

PMID- 29333179
TI  - Liensinine and Nuciferine, Bioactive Components of Nelumbo nucifera, Inhibit the
      Growth of Breast Cancer Cells and Breast Cancer-Associated Bone Loss.
AB  - Once breast cancer cells grow aggressively and become lodged in the skeleton
      through migration and invasion, they interact with bone microenvironment and
      accelerate much more tumor growth and bone destruction. We investigated whether
      liensinine and nuciferine, major active components in Nelumbo nucifera (lotus),
      could prevent breast cancer cell-mediated bone destruction. Liensinine and
      nuciferine inhibited the growth of MDA-MB-231 and MCF-7 human breast cancer cells
      by inducing apoptosis and inhibiting proliferation via cell cycle arrest.
      Liensinine treatment led to the increased Bax/Bcl-2 ratio, activation of caspase
      3, and subsequent cleavage of PARP. Liensinine also displayed significant
      inhibition on the migration and invasion of both MDA-MB-231 and MCF-7 human
      breast cancer cells compared with nuciferine. In addition, liensinine and
      nuciferine inhibited the receptor activator of nuclear factor kappa-B ligand-
      (RANKL-) induced osteoclast differentiation in mouse bone marrow macrophage cells
      and mature osteoclast-mediated bone resorption. Furthermore, oral administration
      of liensinine reduced the osteolysis in nude mice with intratibial injection of
      MDA-MB-231 cells. Collectively, liensinine and nuciferine may be promising
      candidates for preventing and treating breast cancer bone metastasis and the
      resulting osteolytic bone loss by targeting both cancer cells and osteoclasts.
      Liensinine has more potent anticancer and antibone resorptive activities than
      nuciferine.

PMID- 29333180
TI  - Retracted: Silymarin Accelerates Liver Regeneration after Partial Hepatectomy.
AB  - [This retracts the article DOI: 10.1155/2015/603529.].

PMID- 29333181
TI  - Study on the Inhibitory Effects of Ephedra Aconite Asarum Decoction on LPS
      Induced Dendritic Cells.
AB  - Dendritic cells (DCs) can secrete cytokines stimulated by lipopolysaccharide
      (LPS), which leads to not just acute inflammatory responses but also Th1
      polarization. Furtherly, chronic inflammation or autoimmune diseases could be
      triggered. As a classic Traditional Chinese Medicine formula, Ephedra Aconite
      Asarum Decoction with the main ingredients of ephedrine and hypaconitine can show
      effect on anti-inflammation and immunoregulation. But it remains unclear whether
      Ephedra Aconite Asarum Decoction controls DCs. In this study, we investigated the
      effects of Ephedra Aconite Asarum Decoction on LPS-induced bone marrow-derived
      DCs (BMDCs) in vitro. We found that Ephedra Aconite Asarum Decoction lowered
      surface costimulators on DCs and reduced the expression of Th1 type cytokines.
      Yet it is slightly beneficial for shifting to Th2. Our work reveals that the
      Ephedra Aconite Asarum Decoction can regulate Th1 inflammation through
      intervening DCs.

PMID- 29333182
TI  - Corrigendum to "Ginkgolide C Suppresses Adipogenesis in 3T3-L1 Adipocytes via the
      AMPK Signaling Pathway".
AB  - [This corrects the article DOI: 10.1155/2015/298635.].

PMID- 29333183
TI  - Retracted: The Effect of Elephantopus scaber L. on Liver Regeneration after
      Partial Hepatectomy.
AB  - [This retracts the article DOI: 10.1155/2013/369180.].

PMID- 29333184
TI  - Meta-Analysis of Chinese Traditional Medicine Bushen Huoxue Prescription for
      Endometriosis Treatment.
AB  - Objectives: To evaluate the efficacy and safety of Bushen Huoxue prescription
      (BSHXP) for endometriosis. Methods: A meta-analysis was performed, and studies
      were searched from the seven databases from the date of database establishment to
      April 30, 2017. Randomized controlled trials (RCTs) that explored the efficacy
      and safety of BSHXP for patients with endometriosis were included. Two assessors
      independently reviewed each trial. The Cochrane Risk of Bias assessment tool was
      used for quality assessment. Results: In the 13 included studies, the total
      effectiveness rates of BSHXP were higher than those of Western medicine (RR,
      1.55; 95% CI, 1.03-2.32; P = 0.04), but the dysmenorrhea alleviation rates of the
      two treatments did not significantly differ (RR, 1.28; 95% CI, 0.70-2.34; P =
      0.42). The pregnancy rates of BSHXP were also higher than those of hormone
      therapy (RR, 1.99; 95% CI, 1.17-3.39; P = 0.01). However, whether BSHXP is more
      effective than Western medicine in diminishing endometriotic cyst remains
      unknown. Conclusions: Our study provides evidence that BSHXP is effective and
      safe for endometriosis, but this evidence is inconclusive because of the low
      methodological quality of the included RCTs. Our findings suggest that BSHXP is
      an alternative drug for endometriosis, but it should be further examined in
      future clinical research.

PMID- 29333185
TI  - Antidepressant-Like Effect of Selected Egyptian Cultivars of Flaxseed Oil on a
      Rodent Model of Postpartum Depression.
AB  - Flaxseed (Linum usitatissimum L.) is a multipurpose crop with health promoting
      potential. This study was undertaken to investigate the fatty acid profile and
      yield of fixed oil of six Egyptian flaxseed cultivars. The selected cultivars
      with the highest content of polyunsaturated fatty acids (PUFAs) (G9 and G10) were
      assessed for their antidepressant-like effect in rat model of postpartum
      depression (PPD) induced by hormone-simulated pregnancy followed by hormone
      withdrawal and compared to fluoxetine. As compared to control group,
      administration of G9 and G10 (270 mg/kg/day, p.o) for two weeks during the
      postpartum period can alleviate anxiety and depressive-like behaviors and
      biochemical changes in PPD-induced rats. This was confirmed by evaluation of
      anxiety-like behaviors (elevated plus maze, open field test, and forced swim test
      tests), in addition to biochemical analysis (brain monoamine oxidase-A,
      corticosterone level, proinflammatory cytokines, and hippocampal redox state). In
      conclusion, flaxseed oil of Egyptian cultivars G9 and G10 exhibited significant
      antidepressant-like effect in rat model of PPD without affecting locomotor
      activity. At the treatment doses, the antidepressant-like activity of Giza 9 oil
      is comparable to fluoxetine.

PMID- 29333186
TI  - Role of Cholinergic Anti-Inflammatory Pathway in Treatment of Intestinal Ischemia
      Reperfusion Injury by Electroacupuncture at Zusanli.
AB  - Electroacupuncture (EA) at Zusanli is a widely used method for the treatment of
      intestinal ischemic disease. The current study attempts to investigate the
      possible mechanism from the point of cholinergic anti-inflammatory pathway (CAP)
      in rats. Thirty rats were divided into five groups: control group, I/R group, EA
      group (I/R + EA), PNU group (I/R + alpha7 nAChR agonist), and alpha-BGT group
      (I/R + EA + alpha7 nAChR antagonist). EA and medicine injection were performed
      immediately after ischemia. After 2 h of reperfusion, blood and intestine samples
      were collected and intestinal histopathological score, mRNA expression of mucosal
      alpha7 nAChR and NF-kappaBp65, and serum cytokine levels (IL-6, TNF-alpha) were
      examined. Compared with the I/R group, the EA group and PNU group could
      significantly attenuate the mucosal damage, promote alpha7 nAChR mRNA expression,
      and reduce levels of NF-kappaBp65, IL-6, and TNF-alpha. Compared with the EA
      group, alpha7 nAChR mRNA was decreased, while concentrations of NF-kappaBp65, IL
      6, and TNF-alpha increased in the alpha-BGT group. EA at Zusanli could inhibit NF
      kappaBp65 and proinflammatory cytokines production after intestinal I/R injury;
      its mechanism may be related to the cholinergic anti-inflammatory pathway.

PMID- 29333187
TI  - Efficacy and Safety of the TCM Qi-Supplementing Therapy in Patients with
      Myasthenia Gravis: A Systematic Review and Meta-Analysis.
AB  - Background: The Traditional Chinese Medicine (TCM) Qi-supplementing therapy has
      been used widely for treating myasthenia gravis (MG) in China. The purpose of
      this meta-analysis was to evaluate the efficacy and safety of Qi-supplementing
      therapy as an adjunctive therapy in MG patients. Methods: Seven electronic
      databases were searched through June 2016. Randomized controlled trials (RCTs)
      evaluating the add-on effect of Qi-supplementing therapy in MG patients were
      included. The outcome measures were the total effective rate, relapse rate, and
      adverse events. Results: Twenty-three RCTs involving 1,691 MG patients were
      included. The included studies were of low-to-moderate quality. Meta-analysis
      showed that Qi-supplementing therapy combined with Western medicine (WM)
      significantly improved the total response rate and reduced the relapse risk
      during 6-24 months of follow-up. Subgroup analysis showed that Qi-supplementing
      therapy only affected the total response rate within the first 6 months of
      treatment. Moreover, the rate of adverse events was lower with the addition of Qi
      supplementing therapy to WM than with WM only. Conclusions: Short-term Qi
      supplementing therapy combined with WM appears to be superior to WM for improving
      the total response rate and reducing the relapse rate. However, more high-quality
      RCTs are warranted owing to methodological flaws of previous trials.

PMID- 29333188
TI  - Dracorhodin Perchlorate Accelerates Cutaneous Wound Healing in Wistar Rats.
AB  - Dracorhodin perchlorate (DP) is extracted from Dragon's blood, which is widely
      used in traditional Chinese medicine, especially in wound healing. The aim of
      this paper is to investigate the influence of DP ointment, which contained DP
      dissolved in DMSO and mixed with Vaseline, on cutaneous wound healing in Wistar
      rats. Forty Wistar rats were divided into two groups: control and DP groups. The
      skin on the back of each rat was punched with two full-thickness wounds and then
      treated with the corresponding drug. After 3, 7, 10, 14, and 21 days, four rats
      were sacrificed for immunological, biochemical, and histological analyses.
      Compared with the control treatment, DP could significantly promote wound
      closure. Histological and biochemical analyses of the skin biopsies also showed
      that DP regulated the expression of inflammatory responses by TNF-alpha and IL
      beta and by supporting wound tissue growth and collagen deposition. Western blot
      revealed that DP could also facilitate the expression of EGF and VEGF proteins.
      In conclusion, DP promotes wound healing.

PMID- 29333189
TI  - Tubular variant of mammary adenomyoepithelioma: Diagnostic challenges and
      cytomorphological correlation in two cases.
AB  - The authors describe the cytomorphologic features of two cases of tubular variant
      of adenomyoepithelioma of the breast that were first examined by fine-needle
      aspiration cytology (FNAC) and diagnosed as fibroadenoma. On retrospective review
      of the cytology, subtle features such as less cohesive epithelial clusters,
      intimate association of clusters of stromal cells with epithelial elements, a
      dominant population of plump-epithelioid naked (myoepithelial) cells, and
      occasional cells with intranuclear inclusions, were noted. Thus, these lesions
      can be diagnostically challenging and cannot be conclusively differentiated from
      either fibroadenoma or tubular adenoma cytologically and the pathologist may only
      be able to give a differential on FNAC. Recognition of the biphasic nature and
      the characteristic overall architecture of the tumors in combination with
      immunohistochemistry are essential to establish the correct diagnosis on biopsy.
      Although most tumors have a benign clinical course, rare instances of local
      recurrence, malignant transformation, and distant metastases have been reported.
      A complete excision with adequate margins would lower the chance of local
      recurrence.

PMID- 29333190
TI  - Fine-needle aspiration of a right neck mass in a 10-year-old boy: Diagnostic
      clues and workup for tumors with small round blue cells.

PMID- 29333191
TI  - Comparative evaluation of six parametric Robinson and three parametric Howell's
      modification of Scarf-BloomRichardson grading method on breast aspirates with
      histopathology: A prospective study.
AB  - Background: Fine needle aspiration cytology (FNAC) is a quick method to assess
      the tumor grade before its removal which will help clinicians to decide on the
      appropriate neo adjuvant therapy. This is essentially true in developing
      countries where core needle biopsy still is not used as a standard practice to
      sample breast carcinoma. Assessment of biological aggressiveness by cytological
      grading (CG) without removing the would be of immense value. The National Cancer
      Institute, Bethesda, sponsored conference had recommended that tumor grading on
      FNA material should be incorporated in cytology reports for prognostication. Aim:
      The present study was carried out to evaluate which among the two, five
      parametric Robinson or three parametric Scarf-BloomRichardson (SBR) cytology
      grading method corresponds better with the histological grading (HG) in breast
      carcinoma. Materials and Methods: FNAC of 150 cases of ductal carcinoma breast
      with subsequent histological confirmation was studied to assess the tumor grade
      on cytology by two distinct methods Robinson and Howell's modification of
      SBRmethod and then correlated with histologic grade. Results: Comparative
      analysis revealed concordance of 76% by Robinson and 68% by SBR with Kappa value
      of 0.6683 and 0.4505 and diagnostic accuracy of 86.7% and 78.7%, respectively.
      Conclusions: We conclude that Robinson method showed a better correlation and
      higher kappa value of agreement in comparison with SBR method. Robinson method of
      CG is simpler, objective, and easily reproducible for grading breast carcinomas.

PMID- 29333192
TI  - 'Haven of safety' and 'secure base': a qualitative inquiry into factors affecting
      child attachment security in Nairobi, Kenya.
AB  - Secure attachment in childhood and adolescence protects children from engagement
      in high risk behaviors and development of mental health problems over the life
      span. Poverty has been shown to create impoverishment in certain aspects of
      caregiving and correspondingly to compromise development of secure attachment in
      children. Nineteen children 8 to 14 years old from two schools in a middle income
      area and an urban informal settlement area of Nairobi were interviewed using an
      adapted Child Attachment Interview (CAI) protocol. CAI was developed to provide a
      glimpse into the 'meta-theories' children have about themselves, parents,
      parenting and their attachment ties with parents and extended family members.
      Narratives obtained with the CAI were analyzed using thematic analysis. Both
      Bowlby's idea of 'secure base' as well as Bronfrenbrenner's 'ecological niche'
      are used as reference points to situate child attachment and parenting practices
      in the larger Kenyan context. We found that with slight linguistic alterations
      CAI can be used to assess attachment security of Kenyan children in this
      particular age range. We also found that the narration ability in both groups of
      children was generally good such that formal coding was possible, despite
      cultural differences. Our analysis suggested differences in narrative quality
      across the children from middle class and lower socio-economic class schools on
      specific themes such as: sensitivity of parenting (main aspects of sensitivity
      were associated with disciplinary methods and child's access to education), birth
      order, parental emotional availability, and severity of inter-parental conflicts
      and child's level of exposure. The paper puts in context a few cultural practices
      such as greater household responsibility accorded to the eldest child and stern
      to harsh disciplinary methods adopted by parents in the Kenyan setting.

PMID- 29333193
TI  - Systematic Review of Community-Engaged Research in Ophthalmology.
AB  - Introduction: Community-engaged research (CEnR) allows researchers and community
      organizations to partner together to improve health outcomes and to decrease
      health disparities. While prevalent in other fields of medicine, it is rarely
      used in ophthalmology. Areas covered: A comprehensive search of Ovid MEDLINE, NLM
      Pubmed, Ovid Embase, Scopus and the Cochrane Library for the Medical Subject
      Headings (MeSH) "Community-based participatory research" and text word variations
      including participatory research, community engagement, community research,
      partnered research, community-institutional relations, CENR, CBPR in addition to
      variations on ophthalmology, eye diseases, vision disorders and eye injuries
      yielded 451 unique references. Two ophthalmologists (KN, PANC) reviewed the
      titles and abstracts and identified 37 relevant studies. Expert consultation
      yielded an additional reference. After reviewing the full texts and excluding non
      English texts, 18 articles met the necessary criteria. The eighteen articles all
      utilized at least one of the nine principles of CEnR. Expert commentary:
      Ophthalmology is perfectly positioned to benefit from CEnR. Increased community
      engagement in ophthalmic research would expand the reach of our work and address
      some of the most difficult problems in vision disparities and outcomes.

PMID- 29333194
TI  - Transient Dynamics Simulation of Airflow in a CT-Scanned Human Airway Tree: More
      or Fewer Terminal Bronchi?
AB  - Using computational fluid dynamics (CFD) method, the feasibility of simulating
      transient airflow in a CT-based airway tree with more than 100 outlets for a
      whole respiratory period is studied, and the influence of truncations of terminal
      bronchi on CFD characteristics is investigated. After an airway model with 122
      outlets is extracted from CT images, the transient airflow is simulated. Spatial
      and temporal variations of flow velocity, wall pressure, and wall shear stress
      are presented; the flow pattern and lobar distribution of air are gotten as well.
      All results are compared with those of a truncated model with 22 outlets. It is
      found that the flow pattern shows lobar heterogeneity that the near-wall air in
      the trachea is inhaled into the upper lobe while the center flow enters the other
      lobes, and the lobar distribution of air is significantly correlated with the
      outlet area ratio. The truncation decreases airflow to right and left upper lobes
      and increases the deviation of airflow distributions between inspiration and
      expiration. Simulating the transient airflow in an airway tree model with 122
      bronchi using CFD is feasible. The model with more terminal bronchi decreases the
      difference between the lobar distributions at inspiration and at expiration.

PMID- 29333195
TI  - Corrigendum to "Development of a Patient-Specific Finite Element Model for
      Predicting Implant Failure in Pelvic Ring Fracture Fixation".
AB  - [This corrects the article DOI: 10.1155/2017/9403821.].

PMID- 29333196
TI  - Brief report: Reduced anxiety following Pivotal Response Treatment in young
      children with Autism Spectrum Disorder.
AB  - Up to 40% of children with Autism Spectrum Disorder (ASD) exhibit co-occurring
      anxiety symptoms. Despite recent success in mitigating anxiety symptoms in school
      aged children with ASD (mean age >9 years) using adapted versions of Cognitive
      Behavioural Therapy, little is known about potential treatment outcomes for
      younger children. To address the gap in the literature, this open-label study
      evaluated change in anxiety following a 16-week open-label trial of Pivotal
      Response Treatment (PRT) in children with ASD aged 4-8 years. PRT is a
      behavioural treatment based on the principles of Applied Behaviour Analysis and
      has a primary aim of increasing social communication skills in children with ASD
      through natural reinforcements. To minimise conflation of anxiety and other co
      occurring symptoms such as disruptive behaviour and attention-deficit
      hyperactivity disorder, we measured anxiety using the autism anxiety subscale of
      the Child and Adolescent Symptom Inventory (CASI) devised by Sukhodolsky et al.
      (2008). We observed significant anxiety reduction over 16-weeks of PRT.
      Furthermore, anxiety reduction was independent of changes in autism symptom
      severity. This study shows promising results for PRT as an intervention for
      reducing anxiety in young children with ASD.

PMID- 29333197
TI  - Solving moment hierarchies for chemical reaction networks.
AB  - The study of chemical reaction networks (CRN's) is a very active field. Earlier
      well-known results (Feinberg 1987 Chem. Enc. Sci. 42 2229, Anderson et al 2010
      Bull. Math. Biol. 72 1947) identify a topological quantity called deficiency, for
      any CRN, which, when exactly equal to zero, leads to a unique factorized steady
      state for these networks. No results exist however for the steady states of non
      zero-deficiency networks. In this paper, we show how to write the full moment
      hierarchy for any non-zero-deficiency CRN obeying mass-action kinetics, in terms
      of equations for the factorial moments. Using these, we can recursively predict
      values for lower moments from higher moments, reversing the procedure usually
      used to solve moment hierarchies. We show, for nontrivial examples, that in this
      manner we can predict any moment of interest, for CRN's with non-zero deficiency
      and non-factorizable steady states.

PMID- 29333198
TI  - Response of Pacific-sector Antarctic ice shelves to the El Nino/Southern
      Oscillation.
AB  - Satellite observations over the past two decades have revealed increasing loss of
      grounded ice in West Antarctica, associated with floating ice shelves that have
      been thinning. Thinning reduces an ice-shelf's ability to restrain grounded-ice
      discharge, yet our understanding of the climate processes that drive mass changes
      is limited. Here, we use ice-shelf height data from four satellite altimeter
      missions (1994-2017) to show a direct link between ice-shelf-height variability
      in the Antarctic Pacific sector and changes in regional atmospheric circulation
      driven by the El Nino-Southern Oscillation. This link is strongest from Dotson to
      Ross ice shelves and weaker elsewhere. During intense El Nino years, height
      increase by accumulation exceeds the height decrease by basal melting, but net
      ice-shelf mass declines as basal ice loss exceeds lower-density snow gain. Our
      results demonstrate a substantial response of Amundsen Sea ice shelves to global
      and regional climate variability, with rates of change in height and mass on
      interannual timescales that can be comparable to the longer-term trend, and with
      mass changes from surface accumulation offsetting a significant fraction of the
      changes in basal melting. This implies that ice-shelf height and mass variability
      will increase as interannual atmospheric variability increases in a warming
      climate.

PMID- 29333199
TI  - Effects of the dietary approaches to stop hypertension (DASH) diet on glucose
      variability in youth with Type 1 diabetes.
AB  - Objective: Glucose variability (GV) independently increases risk for vascular
      events in patients with diabetes. The Dietary Approaches to Stop Hypertension
      (DASH) dietary pattern emphasizes fruits, vegetables, whole grains, lean meats,
      and low fat dairy and has the potential to reduce postprandial blood glucose (BG)
      excursions, however, its effect on GV is not known. The purpose of this work was
      to assess feasibility and collect preliminary data on the efficacy of the DASH
      diet on GV in adolescents with type 1 diabetes (T1D). Methods: Twenty one
      adolescents recruited from the Diabetes Center of Cincinnati Children's Hospital
      Medical Center with T1D (11-17y) participated in one of two phases of a
      controlled feeding study. The first phase tested the acceptability and blood
      glucose response to a traditional DASH diet (DASH) and the second phase tested a
      DASH diet specifically modified for diabetes (DASH-D) to improve glucose response
      to meals. For each phase, participants consumed first their usual diet, and then
      a controlled DASH diet while wearing continuous glucose monitoring (CGM) systems
      for 3 days of each diet. All foods were provided to the patients during the DASH
      dietary periods and 24 h dietary recalls were conducted during the usual diet
      periods to assess daily intake. Results: Sixteen participants (14.1 +/- 2.2y)
      were included in final analyses (DASH n=7, DASH-D n=9). Both DASH diets were
      significantly higher in fruits, vegetables, fiber, vitamin A, and % energy from
      protein than usual intakes. DASH was higher in carbohydrate (CHO) (60 vs. 50%)
      and lower in fat (21 vs. 36%) than usual intake, resulting in higher GV (Standard
      Deviation and Lability Index) and more low BG excursions (3 +/- 2.8 vs. 7.1 +/-
      3.3, p=0.024). DASH-D was modified to better match CHO and fat content of
      patients' usual intakes in phase 1 (50/30/20 for CHO/fat/pro respectively, which
      resulted in no difference in GV between DASH-D and usual intake. There were also
      trends for lower average BG (144.1 vs. 168.9, p=0.072) and less percentage of
      time spent in the hyperglycemic range (39.3 +/- 25.5 vs. 54.1 +/- 19.4, p=0.07)
      on DASH-D compared to usual intake. Conclusion: The DASH dietary pattern tended
      to result in less hyperglycemia and an overall lower BG compared to usual care.
      Modifying a traditional DASH diet by increasing heart healthy fats improves
      glycemic response to DASH and may be beneficial for long term cardiovascular
      benefits in youth with T1D.

PMID- 29333200
TI  - Perceptions of Mindfulness in a Low-income, Primarily African American Treatment
      Seeking Sample.
AB  - Individuals with low socioeconomic status (SES) and members of racial/ethnic
      minority groups often experience profound disparities in mental health and
      physical well-being. Mindfulness-based interventions show promise for improving
      mood and health behaviors in higher-SES and non-Latino White populations.
      However, research is needed to explore what types of adaptations, if any, are
      needed to best support underserved populations. This study used qualitative
      methods to gain information about a) perceptions of mindfulness, b) experiences
      with meditation, c) barriers to practicing mindfulness, and d) recommendations
      for tailoring mindfulness-based interventions in a low-income, primarily African
      American treatment-seeking sample. Eight focus groups were conducted with 32
      adults (16 men and 16 women) currently receiving services at a community mental
      health center. Most participants (91%) were African American. Focus group data
      were transcribed and analyzed using NVivo 10. A team of coders reviewed the
      transcripts to identify salient themes. Relevant themes included beliefs that
      mindfulness practice might improve mental health (e.g., managing stress and anger
      more effectively) and physical health (e.g., improving sleep and chronic pain,
      promoting healthier behaviors). Participants also discussed ways in which
      mindfulness might be consistent with, and even enhance, their religious and
      spiritual practices. Results could be helpful in tailoring mindfulness-based
      treatments to optimize feasibility and effectiveness for low-SES adults receiving
      mental health services.

PMID- 29333201
TI  - Dispositional Mindfulness, Shame, and Compulsive Sexual Behaviors among Men in
      Residential Treatment for Substance Use Disorders.
AB  - Approximately 31% of men in treatment for a substance use disorders (SUD) engage
      in compulsive sexual behavior (CSB). Shame, a well-documented consequence of CSB,
      increases the likelihood of relapse following treatment for SUDs. Despite the
      risk of relapse, prior research has not investigated factors that may attenuate
      the relation between CSB and shame. Dispositional mindfulness is one such factor
      known to mitigate shame. However, researchers have yet to examine dispositional
      mindfulness as a moderator of the relationship between CSB and shame among a
      sample of men in treatment for SUDs. In an effort to inform intervention efforts,
      the present study aimed to investigate the hypothesis that CSB would not relate
      to shame among men with high, as opposed to low, levels of dispositional
      mindfulness. The present study reviewed medical records of 184 men in residential
      treatment for SUDs who completed cross-sectional measures of shame, CSB,
      dispositional mindfulness, and substance use problems. Results demonstrated a
      significant interaction between CSB and dispositional mindfulness such that CSB
      positively related to shame at low, but not mean or high, levels of dispositional
      mindfulness. These results support and extend previous mindfulness and CSB
      treatment research. Findings suggested that intervention efforts for CSB may
      benefit from increasing dispositional mindfulness in an effort to reduce shame
      related cognitions.

PMID- 29333202
TI  - Elasto-inertial migration of deformable capsules in a microchannel.
AB  - In this paper, we study the dynamics of deformable cells in a channel flow of
      Newtonian and polymeric fluids and unravel the effects of deformability,
      elasticity, inertia, and size on the cell motion. We investigate the role of
      polymeric fluids on the cell migration behavior and the performance of inertial
      microfluidic devices. Our results show that the equilibrium position of the cell
      is on the channel diagonal, in contrast to that of rigid particles, which is on
      the center of the channel faces for the same range of Reynolds number. A constant
      viscosity polymeric fluid, modeled using an Oldroyd-B constitutive equation,
      drives the cells toward the channel centerline, while a shear-thinning polymeric
      fluid, modeled using a Giesekus constitutive equation, pushes the cells toward
      the channel wall. The findings of this paper suggest that the addition of
      polymers in microfluidic devices can be used to enhance the throughput of cell
      focusing and separation devices at a low cost. This study provides an insight on
      the role of rheological properties of the fluid and the ways that they can be
      tuned to control the focal position of the cells.

PMID- 29333203
TI  - Biomimetic microfluidic platform for the quantification of transient endothelial
      monolayer permeability and therapeutic transport under mimicked cancerous
      conditions.
AB  - Therapeutic delivery from microvasculature to cancerous sites is influenced by
      many factors including endothelial permeability, vascular flow rates/pressures,
      cancer secretion of cytokines and permeabilizing agents, and characteristics of
      the chosen therapeutics. This work uses bi-layer microfluidics capable of
      studying dye and therapeutic transport from a simulated vessel to a cancerous
      region while allowing for direct visualization and quantification of endothelial
      permeability. 2.5 to 13 times greater dye transport was observed when utilizing
      small dye sizes (FITC) when compared to larger molecules (FITC-Dextran 4 kDa and
      FITC-Dextran 70 kDa), respectively. The use of lower flow rates/pressures is
      shown to improve dye transport by factors ranging from 2.5 to 5 times, which
      result from increased dye diffusion times within the system. Furthermore,
      subjecting confluent endothelial monolayers to cancerous cells resulted in
      increased levels of vascular permeability. Situations of cancer induced increases
      in vascular permeability are shown to facilitate enhanced dye transport when
      compared to non-diseased endothelial monolayers. Subsequent introduction of
      paclitaxel or doxorubicin into the system was shown to kill cancerous cells
      resulting in the recovery of endothelial confluency overtime. The response of
      endothelial cells to paclitaxel and doxorubicin is quantified to understand the
      direct influence of anti-cancer therapeutics on endothelial growth and
      permeability. Introduction of therapeutics into the system showed the recovery of
      endothelial confluency and dye transport back to conditions experienced prior to
      cancer cell introduction after 120 h of continuous treatment. Overall, the system
      has been utilized to show that therapeutic transport to cancerous sites depends
      on the size of the chosen therapeutic, the flow rate/pressure established within
      the vasculature, and the degree of cancer induced endothelial permeability. In
      addition, treatment of the cancerous region has been demonstrated with anti
      cancer therapeutics, which are shown to influence vascular permeability in direct
      (therapeutics themselves) and indirect (death of cancer cells) manners. Lastly,
      the system presented in this work is believed to function as a versatile testing
      platform for future anti-cancer therapeutic testing and development.

PMID- 29333204
TI  - Aggressive prostate cancer cell nuclei have reduced stiffness.
AB  - It has been hypothesized that highly metastatic cancer cells have softer nuclei
      and hence would travel faster through confining environments. Our goal was to
      prove this untested hypothesis for prostate cells. Our nuclear creep experiments
      using a microfluidic channel with a narrow constriction show that stiffness of
      aggressive immortalized prostate cancer nuclei is significantly lower than that
      of immortalized normal cell nuclei and hence can be a convenient malignancy
      marker. Nuclear stiffness is found to be the highest for cells expressing high
      levels of lamin A/C but lowest for cells expressing low lamin A/C levels.
      Decreased chromatin condensation found in softer nuclei suggests that the former
      can also be a marker for aggressive cancers.

PMID- 29333205
TI  - High aspect ratio induced spontaneous generation of monodisperse picolitre
      droplets for digital PCR.
AB  - Droplet microfluidics, which involves micrometer-sized emulsion droplets on a
      microfabricated platform, has been demonstrated as a unique system for many
      biological and chemical applications. Robust and scalable generation of
      monodisperse droplets at high throughput is of fundamental importance for droplet
      microfluidics. Classic designs for droplet generation employ shear fluid dynamics
      to induce the breakup of droplets in a two-phase flow and the droplet size is
      sensitive to flow rate fluctuations, often resulting in polydispersity. In this
      paper, we show spontaneous emulsification by a high aspect ratio (>3.5)
      rectangular nozzle structure. Due to the confinement and abrupt change of the
      structure, a Laplace pressure difference is generated between the dispersed and
      continuous phases, and causes the thread thinning and droplet pinch-off without
      the need to precisely control external flow conditions. A high-throughput droplet
      generator was developed by parallelization of a massive number of the basic
      structures. This device enabled facile and rapid partition of aqueous samples
      into millions of uniform picolitre droplets in oil. Using this device, on-chip
      droplet-based digital polymerase chain reaction (PCR) was performed for absolute
      quantification of rare genes with a wide dynamic range.

PMID- 29333206
TI  - Nonlinear Joint Latent Variable Models and Integrative Tumor Subtype Discovery.
AB  - Integrative analysis has been used to identify clusters by integrating data of
      disparate types, such as deoxyribonucleic acid (DNA) copy number alterations and
      DNA methylation changes for discovering novel subtypes of tumors. Most existing
      integrative analysis methods are based on joint latent variable models, which are
      generally divided into two classes: joint factor analysis and joint mixture
      modeling, with continuous and discrete parameterizations of the latent variables
      respectively. Despite recent progresses, many issues remain. In particular,
      existing integration methods based on joint factor analysis may be inadequate to
      model multiple clusters due to the unimodality of the assumed Gaussian
      distribution, while those based on joint mixture modeling may not have the
      ability for dimension reduction and/or feature selection. In this paper, we
      employ a nonlinear joint latent variable model to allow for flexible modeling
      that can account for multiple clusters as well as conduct dimension reduction and
      feature selection. We propose a method, called integrative and regularized
      generative topographic mapping (irGTM), to perform simultaneous dimension
      reduction across multiple types of data while achieving feature selection
      separately for each data type. Simulations are performed to examine the operating
      characteristics of the methods, in which the proposed method compares favorably
      against the popular iCluster that is based on a linear joint latent variable
      model. Finally, a glioblastoma multiforme (GBM) dataset is examined.

PMID- 29333207
TI  - Development and Feasibility of a Robotic Laparoscopic Clipping Tool for Wound
      Closure and Anastomosis.
AB  - This paper reports the design, development, and initial evaluation of a robotic
      laparoscopic clipping tool for single manipulator wound closure and anastomosis
      (tubular reconnection). The tool deploys biodegradable clips and clasps with the
      goal of (i) integrating grasping and suturing into a single device for single
      hand or manipulator use, (ii) applying the equivalent of interrupted sutures
      without the need of managing suture thread, and (iii) allowing for full six
      degrees-of-freedom (DOFs) laparoscopic control when mounted on a robot arm. The
      specifications, workflow, and detailed design of the robotic laparoscopic tool
      and injection molded bio-absorbable T shaped clip and locking clasp are reported.
      The clipping tool integrates forceps to grab and stabilize tissue and a clip and
      clasp applier to approximate and fixate the tissue. A curved needle is advanced
      on a circular needle path and picks up and drags clips through tissue. The clip
      is then tightened through the tissue and a clasp is clamped around the clip,
      before the clip is released from the needle. Results of several bench test runs
      of the tool show: (a) repeatable circular needle drive, (b) successful pick-up
      and deployment of clips, (c) successful shear of the clip to release the clip
      from the needle, and (d) closure of clasp on clip with an average of 2.0 N
      holding force. These data indicate that the robotic laparoscopic clipping tool
      could be used for laparoscopic wound closure and anastomosis.

PMID- 29333208
TI  - Integrating Cadaver Needle Forces Into a Haptic Robotic Simulator.
AB  - Accurate force simulation is essential to haptic simulators for surgical
      training. Factors such as tissue inhomogeneity pose unique challenges for
      simulating needle forces. To aid in the development of haptic needle insertion
      simulators, a handheld force sensing syringe was created to measure the motion
      and forces of needle insertions. Five needle insertions were performed into the
      neck of a cadaver using the force sensing syringe. Based on these measurements a
      piecewise exponential needle force characterization, was implemented into a
      haptic central venous catheterization (CVC) simulator. The haptic simulator was
      evaluated through a survey of expert surgeons, fellows, and residents. The
      maximum needle insertion forces measured ranged from 2.02 N to 1.20 N. With this
      information, four characterizations were created representing average, muscular,
      obese, and thin patients. The median survey results showed that users
      statistically agreed that "the robotic system made me sensitive to how patient
      anatomy impacts the force required to advance needles in the human body." The
      force sensing syringe captured force and position information. The information
      gained from this syringe was able to be implemented into a haptic simulator for
      CVC insertions, showing its utility. Survey results showed that experts, fellows,
      and residents had an overall positive outlook on the haptic simulator's ability
      to teach haptic skills.

PMID- 29333209
TI  - ?
AB  - [This corrects the article DOI: 10.11604/pamj.2016.25.142.7193.].

PMID- 29333210
TI  - Bayesian analysis of stochastic volatility-in-mean model with leverage and
      asymmetrically heavy-tailed error using generalized hyperbolic skew Student's t
      distribution.
AB  - A stochastic volatility-in-mean model with correlated errors using the
      generalized hyperbolic skew Student-t (GHST) distribution provides a robust
      alternative to the parameter estimation for daily stock returns in the absence of
      normality. An efficient Markov chain Monte Carlo (MCMC) sampling algorithm is
      developed for parameter estimation. The deviance information, the Bayesian
      predictive information and the log-predictive score criterion are used to assess
      the fit of the proposed model. The proposed method is applied to an analysis of
      the daily stock return data from the Standard & Poor's 500 index (S&P 500). The
      empirical results reveal that the stochastic volatility-in-mean model with
      correlated errors and GH-ST distribution leads to a significant improvement in
      the goodness-of-fit for the S&P 500 index returns dataset over the usual normal
      model.

PMID- 29333211
TI  - Pomegranate Juice Prevents the Formation of Lung Nodules Secondary to Chronic
      Cigarette Smoke Exposure in an Animal Model.
AB  - Background: Cigarette smoke (CS) induces an oxidative stress, DNA damage, and
      lung cancer. Pomegranate juice (PJ) possess potent antioxidant activity
      attributed to its polyphenols. We investigated whether PJ supplementation would
      prevent the formation of lung nodules, attenuate mitotic activity, and reduce
      hypoxia-inducible factor-1alpha (HIF-1alpha) expression secondary to CS exposure
      in an animal model. Methods: Mice were divided into: Control group, CS group, CS
      + PJ group, and PJ-only group. CS and CS + PJ were exposed to CS, 5 days per
      week, for a total of 5 months. Animals were then housed for additional four
      months. CS + PJ and PJ groups received PJ throughout the experiment period while
      others received placebo. At the end of the experiment, the incidence of lung
      nodules was assessed by (1) histological analysis, (2) mitotic activity
      [measurement of PHH3 antibodies], and (3) measurement of HIF-1alpha expression.
      Results: The incidence of lung nodules was significantly increased in CS. CS
      exposure significantly increased PHH3 and HIF-1alpha expression. PJ
      supplementation attenuated the formation of lung nodules and reduced PHH3 and HIF
      1alpha expression. Conclusion: PJ supplementation significantly decreased the
      incidence of lung cancer, secondary to CS, prevented the formation of lung
      nodules, and reduced mitotic activity and HIF-1alpha expression in an animal
      model.

PMID- 29333212
TI  - Effect of Bioactive Compound of Aronia melanocarpa on Cardiovascular System in
      Experimental Hypertension.
AB  - Aronia melanocarpa has attracted scientific interest due to its dense contents of
      different polyphenols. We aimed to analyse effects of Aronia melanocarpa (AME)
      extract on blood pressure (BP), lipid peroxidation, cytokine level, total NOS
      activity in the left ventricle (LV), and aorta of L-NAME-induced hypertensive
      rats. 12-week-old male WKY rats were assigned to the control group and groups
      treated with AME extract (57.90 mg/kg/day), L-NAME (40 mg/kg/day), or combination
      of L-NAME (40 mg/kg/day) and AME (57.90 mg/kg/day) in tap water for 3 weeks. NOS
      activity, eNOS protein expression, and conjugated diene (CD) concentration were
      determined in the LV and aorta. After 3 weeks of L-NAME treatment, BP was
      increased by 28% and concomitant treatment with AME reduced it by 21%. NOS
      activity of the LV and aorta in the L-NAME group was decreased by about 40%,
      while AME increased it almost on the control level. AME-induced eNOS upregulation
      may contribute to increase NOS activity. Moreover, AME decreased CD concentration
      in the LV and aorta and TNF-alpha and IL-6 production in the plasma were
      increased by L-NAME treatment. In conclusion, our results showed that active
      substances of Aronia melanocarpa may have a positive effect on blood pressure,
      NOS activity, and proinflammatory processes in L-NAME-induced hypertension.

PMID- 29333214
TI  - Cytoprotective Effects of Cell-Permeable Bifunctional Antioxidant Enzyme, GST-TAT
      SOD, against Cisplatin-Induced Cell Damage.
AB  - GST-TAT-SOD, a cell-permeable bifunctional antioxidant enzyme, is a potential
      selective radioprotector. This study aimed to investigate the cytoprotective
      activity of GST-TAT-SOD against cisplatin-induced damage. The current study
      showed that cisplatin induced the formation of reactive oxygen species in normal
      L-02 cells. GST-TAT-SOD (2000 U/mL) executed its antioxidant role by directly
      scavenging excess intracellular free radicals and augmenting cellular antioxidant
      defense such as reducing MDA level, enhancing the SOD activity, GST activity, and
      T-AOC. Thus, it suppressed the growth inhibition and apoptosis of cisplatin
      treated normal cells. Meanwhile, the growth inhibition of tumor cells (SMMC-7721)
      caused by cisplatin was unaffected by GST-TAT-SOD pretreatment. GST-SOD, as a
      comparison, seemed to be powerless for related indicators as it could not enter
      into cells without cell-permeating peptide. These results suggest that GST-TAT
      SOD might be a potential cytoprotective agent for cisplatin-induced side effects.

PMID- 29333217
TI  - Gender Differences in Clinical Profiles of Stress-Induced Cardiomyopathy.
AB  - Background: Although stress-induced cardiomyopathy (SCMP) is reported to be more
      common in women, little is known about gender differences in patients with SCMP.
      The aim of the study was to describe clinical features of patients with SCMP
      according to gender. Methods: One hundred and three patients diagnosed with
      definite SCMP at a single tertiary institute from January 1997 to August 2014
      were enrolled. SCMP was more common in women than in men. Results: Age at
      presentation was not significantly different between the two groups (p = 0.758).
      Preceding physical stress, especially acute medical illness, was more common in
      male patients (p = 0.014), whereas emotional stress was more common in female
      patients (p = 0.016). Severity of medical illness classified by the Acute
      Physiology and Chronic Health Evaluation (APACHE) II score at the time of SCMP
      diagnosis was not significantly different between men and women (p = 0.752).
      Clinical characteristics, including symptoms, laboratory and electrocardiographic
      findings, were similar. However, pump failure was more severe in men (p = 0.024).
      Clinical outcomes were not statistically different (p = 0.220). Preceding
      physical stress and lower left ventricular systolic function after 2 months were
      independent risk factors for all-cause mortality for both genders. Women with an
      APACHE II score >= 15 and men with reduced left ventricular ejection fraction
      after 2 months had a greater risk of poor prognosis. Conclusion: SCMP was more
      common in female patients. Female patients more commonly experienced preceding
      emotional stress, whereas physical stress was more common in male patients.
      Systolic dysfunction was more severe in men. Long-term clinical outcomes appeared
      to be similar between men and women.

PMID- 29333216
TI  - Salidroside Inhibits HMGB1 Acetylation and Release through Upregulation of SirT1
      during Inflammation.
AB  - HMGB1, a highly conserved nonhistone DNA-binding protein, plays an important role
      in inflammatory diseases. Once released to the extracellular space, HMGB1 acts as
      a proinflammatory cytokine that triggers inflammatory reaction. Our previous
      study showed that salidroside exerts anti-inflammatory effect via inhibiting the
      JAK2-STAT3 signalling pathway. However, whether salidroside inhibits the release
      of HMGB1 is still unclear. In this study, we aim to study the effects of
      salidroside on HMGB1 release and then investigate the potential molecular
      mechanisms. In an experimental rat model of sepsis caused by CLP, salidroside
      administration significantly attenuated lung injury and reduced the serum HMGB1
      level. In RAW264.7 cells, we investigated the effects of salidroside on LPS
      induced HMGB1 release and then explored the underlying molecular mechanisms. We
      found that salidroside significantly inhibited LPS-induced HMGB1 release, and the
      inhibitory effect was correlated with the HMGB1 acetylation levels. Mechanismly,
      salidroside inhibits HMGB1 acetylation through the AMPK-SirT1 pathway. In
      addition, SirT1 overexpression attenuated LPS-induced HMGB1 acetylation and
      nucleocytoplasmic translocation. Furthermore, in SirT1 shRNA plasmid-transfected
      cells, salidroside treatment enhanced SirT1 expression and reduced LPS-activated
      HMGB1 acetylation and nucleocytoplasmic translocation. Collectively, these
      results demonstrated that salidroside might reduce HMGB1 release through the AMPK
      SirT1 signalling pathway and suppress HMGB1 acetylation and nucleocytoplasmic
      translocation.

PMID- 29333218
TI  - Impact of Mindfulness Based Stress Reduction Therapy on Myocardial Function and
      Endothelial Dysfunction in Female Patients with Microvascular Angina.
AB  - Background: Mindfulness-based stress reduction (MBSR) is a structured group
      program that employs mindfulness meditation to alleviate suffering associated
      with physical, psychosomatic, and psychiatric disorders. In this study, we
      investigate the impact of MBSR on left ventricular (LV) and endothelial function
      in female patients with microvascular angina. Methods: A total of 34 female
      patients (mean age 52.2 +/- 13.8 years) diagnosed with microvascular angina
      underwent a MBSR program with anti-anginal medication for 8 weeks. The global
      longitudinal strain (GLS) of the LV was used as a parameter to assess myocardial
      function and reactive brachial flow-mediated dilatation (FMD) was used to assess
      endothelial function. Symptoms were analyzed by the Symptom Checklist 90 Revised
      to determine emotional stress. Changes in GLS and FMD between baseline and post
      MBSR were analyzed. Results: After 8 weeks of programmed MBSR treatment, stress
      parameters were significantly decreased. In addition, GLS (-19.5 +/- 2.1% vs. 
      16.6 +/- 2.5%, p < 0.001) and reactive FMD significantly improved (8.9 +/- 3.0%
      vs. 6.9 +/- 2.6%, p = 0.005) after MBSR compared to baseline. The changes in GLS
      correlated to changes in FMD (r = 0.120, p = 0.340) and with the changes in most
      stress parameters. Conclusion: MBSR has beneficial impacts on myocardial and
      endothelial function in female patients with microvascular angina.

PMID- 29333213
TI  - Chronic Kidney Disease and Disproportionally Increased Cardiovascular Damage:
      Does Oxidative Stress Explain the Burden?
AB  - Chronic kidney disease (CKD) patients are among the groups at the highest risk
      for cardiovascular disease and significantly shortened remaining lifespan. CKD
      enhances oxidative stress in the organism with ensuing cardiovascular damage.
      Oxidative stress in uremia is the consequence of higher reactive oxygen species
      (ROS) production, whereas attenuated clearance of pro-oxidant substances and
      impaired antioxidant defenses play a complementary role. The pathophysiological
      mechanism underlying the increased ROS production in CKD is at least partly
      mediated by upregulation of the intrarenal angiotensin system. Enhanced oxidative
      stress in the setting of the uremic milieu promotes enzymatic modification of
      circulating lipids and lipoproteins, protein carbamylation, endothelial
      dysfunction via disruption of nitric oxide (NO) pathways, and activation of
      inflammation, thus accelerating atherosclerosis. Left ventricular hypertrophy
      (LVH) and heart failure are hallmarks of CKD. NADPH oxidase activation, xanthine
      oxidase, mitochondrial dysfunction, and NO-ROS are the main oxidative pathways
      leading to LVH and the cardiorenal syndrome. Finally, a subset of antioxidant
      enzymes, the paraoxonases (PON), deserves special attention due to abundant
      clinical evidence accumulated regarding reduced serum PON1 activity in CKD as a
      contributor to the increased burden of cardiovascular disease. Future,
      meticulously designed studies are needed to assess the effects of antioxidant
      therapy on patients with CKD.

PMID- 29333219
TI  - Clinical Utility of Echocardiography for Early and Late Pulmonary Hypertension in
      Preterm Infants: Relation with Bronchopulmonary Dysplasia.
AB  - Background: We evaluated early and late pulmonary hypertension (PH) in preterm
      infants and its relation with bronchopulmonary dysplasia (BPD). Methods: Sixty
      seven preterm infants < 30 weeks' gestation underwent echocardiography within 14
      days after birth for early PH and over 28 days after birth for late PH. We
      measured tricuspid regurgitation (TR) peak velocity, pulse Doppler-derived
      myocardial performance index (MPI) of right ventricle (RV) (RV MPI), eccentricity
      index (EI), and tricuspid annular plane systolic excursion (TAPSE). Results: The
      median gestation age of patients was 27 weeks (range, 23-30 weeks) and median
      birth weight was 1030 g (range, 450-1780 g). TR peak velocity was measured only
      in 19 patients (28.4%). Patients with symptomatic early PH (n = 11) showed a
      significantly lower systolic EI and a significantly higher incidence of RV MPI >
      0.38 and TAPSE < 0.5 cm than patients without PH. The incidence of symptomatic
      early PH was highest in severe BPD, although this was not statistically
      significant. Early echocardiographic parameters are not associated with BPD
      development. Patients with severe BPD showed a significantly higher RV MPI and a
      significantly higher incidence of RV MPI > 0.38 than patients with mild BPD, and
      a significantly lower systolic EI and a significantly higher incidence of
      systolic EI < 0.81 than patients without BPD. Conclusion: Systolic EI, RV MPI,
      and TAPSE were well represented symptomatic early PH, while systolic EI and RV
      MPI could be useful parameters for identifying late PH in preterm infants with
      BPD, even if they did not present PH symptoms.

PMID- 29333221
TI  - Horseshoe-like Shaped Atrial Septal Defects Confirmed on Three-Dimensional
      Transesophageal Echocardiography.

PMID- 29333215
TI  - Markers and Biomarkers of Endothelium: When Something Is Rotten in the State.
AB  - Endothelium is a community of endothelial cells (ECs), which line the blood and
      lymphatic vessels, thus forming an interface between the tissues and the blood or
      lympha. This strategic position of endothelium infers its indispensable
      functional role in controlling vasoregulation, haemostasis, and inflammation. The
      state of endothelium is simultaneously the cause and effect of many diseases, and
      this is coupled with modifications of endothelial phenotype represented by
      markers and with biochemical profile of blood represented by biomarkers. In this
      paper, we briefly review data on the functional role of endothelium, give
      definitions of endothelial markers and biomarkers, touch on the methodological
      approaches for revealing biomarkers, present an implicit role of endothelium in
      some toxicological mechanistic studies, and survey the role of reactive oxygen
      species (ROS) in modulation of endothelial status.

PMID- 29333220
TI  - Outcomes of Left Ventricular Function According to Treatment Response for a
      Patent Ductus Arteriosus in Preterm Infants.
AB  - Background: To evaluate the outcomes of left ventricular (LV) function according
      to treatment response for a hemodynamically significant patent ductus arteriosus
      (hsPDA) in preterm infants. Methods: Echocardiograms of 21 preterm infants born
      at gestational age < 31 weeks obtained at term-equivalent age were
      retrospectively studied. Among preterm infants with a hsPDA, 9 underwent ligation
      after failure of pharmacological closure (ligation group) and 6 experienced
      successful pharmacological closure (medication group). Six preterm infants
      without hsPDA (no-hsPDA group) were studied as controls. LV peak longitudinal
      systolic strain (epsilon) of each infant was retrospectively obtained from
      echocardiograms using velocity vector imaging, along with neonatal outcomes.
      Results: Pharmacological closures were attempted at postnatal day 2-3. In the
      ligation group, the median postnatal age at ligation was 20 days. In the ligation
      group, LV peak longitudinal systolic epsilon was significantly decreased at term
      equivalent age compared to the other groups. Between the medication and no-hsPDA
      groups, LV peak longitudinal systolic epsilon did not differ significantly. Among
      the neonatal outcomes, infants who experienced necrotizing enterocolitis (NEC)
      showed significantly decreased LV peak longitudinal systolic epsilon compared to
      the infants who did not experience NEC . Conclusion: We speculate that in preterm
      infants with an hsPDA, in cases of medical treatment failure, early PDA ligation
      at less than 20 days of postnatal age would be beneficial for preserving LV
      systolic function.

PMID- 29333222
TI  - Congenital Left Atrial Bands with Atrial Fibrillation.

PMID- 29333224
TI  - PRDI-BF1 and PRDI-BF1P isoform expressions correlate with disease status in
      multiple myeloma patients.

PMID- 29333223
TI  - Development of practical functional electrical stimulation cycling systems based
      on an electromyography study of the Cybathlon 2016.
AB  - The purpose of this study was to develop a functional electrical stimulation
      (FES) system based on the motor driving concept for use by spinal cord injury
      patients participating in the FES Cycling competition at the Cybathlon 2016. The
      proposed FES system consists of a low-power control system, a precise processor
      unit, and a 4-channel stimulation unit. Self-adhesive carbon conductive
      electrodes were utilized for stimulation. A 26-year-old SCI patient was qualified
      to participate in the competition. The pilot patient underwent training for 16
      months, which included experience with FES stimulation, performing FES cycling,
      and reducing spasticity, to practice using the FES system. In addition, using
      surface electromyography (EMG) during cycling, the muscle activation pattern for
      generating the stimulation profile was applied and resulted in good performance.
      The best FES cycling performance the pilot achieved was 1000 meters translation
      with the cycling system during twelve minutes of using the FES system. The pilot
      achieved an 1000 meters translation mobility within an average of 16 minutes of
      cycling. Nevertheless, the system must be further investigated regarding muscle
      fatigue and other factors that may affect the stimulation conditions.

PMID- 29333225
TI  - A rare cause of pericardial effusion and ascites: POEMS syndrome.

PMID- 29333226
TI  - Expression of some ATP-binding cassette transporters in acute myeloid leukemia.

PMID- 29333227
TI  - Dasatinib-induced hemorrhagic colitis complicated with cytomegalovirus infection.

PMID- 29333228
TI  - Quantification of polysaccharides fixed to Gram stained slides using lactophenol
      cotton blue and digital image processing.
AB  - I discovered indigo rings and circles in Escherichia coli ATCC(r) 25922TM
      cultures when I added the non-specific polysaccharide stain lactophenol cotton
      blue to Gram stained slides sampled from 96-well plates used to measure
      quantitative growth kinetics (QGK) in virtual colony count antimicrobial assays.
      I attribute the dark blue staining to the presence of capsular polysaccharides
      and bacterial slime associated with clumps of cells.  Since all bacterial cells
      are glycosylated, the majority of cells stain light blue. The contrast between
      dark and light staining is sufficient to enable a digital image processing
      thresholding technique to be quantitative for circular or ring-shaped structures
      that imply the presence of slime fixed to the glass. These polysaccharides
      indicate a possible mechanism of resistance to antimicrobial peptides such as
      defensins, lectins with high affinity for polysaccharides and glycosylated
      proteins.  Adding lactophenol cotton blue to Gram stained slides is a quick and
      inexpensive way to screen cell cultures for bacterial slime, clumps and biofilms,
      revealing details of polysaccharide secretion that are missed using the Gram
      stain alone.  Combined with QGK threshold times, the lactophenol cotton blue Gram
      stain followed by digital image processing provides quantitative information
      useful for quality control, environmental monitoring and detection of clumping
      environmental factors.

PMID- 29333229
TI  - Predicted protein interactions of IFITMs which inhibit Zika virus infection.
AB  - After the first reported case of Zika virus in Brazil, in 2015, a significant
      increase in the reported cases of microcephaly was observed. Microcephaly is a
      neurological condition in which the infant's head is significantly smaller with
      complications in brain development. Recently, two small membrane-associated
      interferon-inducible transmembrane proteins (IFITM1 and IFITM3) have been shown
      to repress members of the flaviviridae family which includes the Zika virus.
      However, the exact mechanisms leading to the inhibition of the virus are yet
      unknown. Here, we assembled an interactome of IFITM1 and IFITM3 with known
      protein-protein interactions (PPIs) collected from publicly available databases
      and novel PPIs predicted using High-confidence Protein-Protein Interaction
      Prediction (HiPPIP) model. We analyzed the functional and pathway associations of
      the interacting proteins, and found that there are several immunity pathways
      (interferon signaling, cd28 signaling in T-helper cells crosstalk between
      dendritic cells and natural killer cells), neuronal pathways (axonal guidance
      signaling, neural tube closure and actin cytoskeleton signaling) and
      developmental pathways that are associated with these interactors. These results
      could help direct future research in elucidating the mechanisms underlying the
      viral immunity to Zika virus and other flaviviruses.

PMID- 29333230
TI  - Funding knowledgebases: Towards a sustainable funding model for the UniProt use
      case.
AB  - Millions of life scientists across the world rely on bioinformatics data
      resources for their research projects. Data resources can be very expensive,
      especially those with a high added value as the expert-curated knowledgebases.
      Despite the increasing need for such highly accurate and reliable sources of
      scientific information, most of them do not have secured funding over the near
      future and often depend on short-term grants that are much shorter than their
      planning horizon. Additionally, they are often evaluated as research projects
      rather than as research infrastructure components. In this work, twelve funding
      models for data resources are described and applied on the case study of the
      Universal Protein Resource (UniProt), a key resource for protein sequences and
      functional information knowledge. We show that most of the models present
      inconsistencies with open access or equity policies, and that while some models
      do not allow to cover the total costs, they could potentially be used as a
      complementary income source. We propose the Infrastructure Model as a sustainable
      and equitable model for all core data resources in the life sciences. With this
      model, funding agencies would set aside a fixed percentage of their research
      grant volumes, which would subsequently be redistributed to core data resources
      according to well-defined selection criteria. This model, compatible with the
      principles of open science, is in agreement with several international
      initiatives such as the Human Frontiers Science Program Organisation (HFSPO) and
      the OECD Global Science Forum (GSF) project. Here, we have estimated that less
      than 1% of the total amount dedicated to research grants in the life sciences
      would be sufficient to cover the costs of the core data resources worldwide,
      including both knowledgebases and deposition databases.

PMID- 29333231
TI  - Using bio.tools to generate and annotate workbench tool descriptions.
AB  - Workbench and workflow systems such as Galaxy, Taverna, Chipster, or Common
      Workflow Language (CWL)-based frameworks, facilitate the access to bioinformatics
      tools in a user-friendly, scalable and reproducible way. Still, the integration
      of tools in such environments remains a cumbersome, time consuming and error
      prone process. A major consequence is the incomplete or outdated description of
      tools that are often missing important information, including parameters and
      metadata such as publication or links to documentation. ToolDog (Tool DescriptiOn
      Generator) facilitates the integration of tools - which have been registered in
      the ELIXIR tools registry (https://bio.tools) - into workbench environments by
      generating tool description templates. ToolDog includes two modules. The first
      module analyses the source code of the bioinformatics software with language
      specific plugins, and generates a skeleton for a Galaxy XML or CWL tool
      description. The second module is dedicated to the enrichment of the generated
      tool description, using metadata provided by bio.tools. This last module can also
      be used on its own to complete or correct existing tool descriptions with missing
      metadata.

PMID- 29333232
TI  - Highlights of the second ISCB Student Council Symposium in Africa, 2017.
AB  - Student Council Symposiums (SCSs) have been found to be very useful for students
      and young researchers. This is especially true given that the events are held
      directly before large international conferences, giving attendees a chance to
      gain exposure and have a warm up to the social nuances involved in attending such
      a meeting. This was the second SCS held in Africa in conjunction with the
      International Society for Computational Biology (ISCB) and the African Society
      for Bioinformatics and Computational Biology's (ASBCB) biennial meeting. This
      symposium was organised by students within the society inside Africa and was held
      on the 10 th of October 2017 in Entebbe, Uganda.

PMID- 29333233
TI  - On the primacy and irreducible nature of first-person versus third-person
      information.
AB  - In this essay, we will support the claim that a) some first-person accounts
      cannot be reduced to their third-person neural and psychophysiological correlates
      and b) that these first-person accounts are the only information to reckon when
      it is necessary to analyse qualia contents. Consequently, for many phenomena,
      first-person accounts are the only reliable source of information available and
      the knowledge of their neural and psychophysical correlates don't offer any
      additional information about them.

PMID- 29333234
TI  - Case Report: Laparoscopic hepatectomy in an elderly patient with major
      comorbidities.
AB  - Surgeons have been hesitant to proceed to hepatectomy in elderly patients, due to
      the higher rate of comorbidities and the reduced reserves. An 81-year-old male
      with hepatocellular carcinoma in the segment VI of the liver and several major
      cardiovascular, pulmonary and metabolic comorbid illnesses was referred to our
      department for treatment. He underwent transarterial chemoembolization of the
      liver tumor and afterwards he underwent laparoscopic resection of the hepatic
      segment VI, with an uneventful postoperative course. This case indicates the
      safety and feasibility of laparoscopic liver resections in older patients, even
      when major comorbidities are present, provided that there is a careful planning
      of therapeutic strategy and operation.

PMID- 29333235
TI  - Case Report: Synchronous primary malignancy including the breast and endometrium.
AB  - Breast and endometrial cancer are the most common types of female cancers, but
      the incidence of both of these malignancies in a single patient is a rare event.
      Multiple primary malignancy has been increasingly reported over the past decade,
      and double primary cancer is considered as the most common type.  In this study,
      we present a 53-year-old woman with synchronous primary malignancy of breast and
      endometrium. This patient had a history of breast and endometrial cancer in her
      family. Mammography and chest CT of the patient revealed a mass in the right
      breast and left supraclavicular region. However, the patient did not want to
      initiate treatment. Subsequently, the patient returned with a chief complaint of
      persistent abnormal vaginal bleeding. Abdominopelvic CT scan of the patient
      revealed a huge soft tissue mass in the pelvic cavity. She underwent
      hysterectomy, and pathology revealed endometrioid carcinoma, which had invaded
      the full thickness of uterine wall. Since this type of malignancy is rare and
      several risk factors are associated with it, it is worth being considered by
      clinicians when making decisions about screening or strategy for prevention.

PMID- 29333237
TI  - Draft genome of tule elk Cervus elaphus nannodes.
AB  - This paper presents the first draft genome of the tule elk ( Cervus elaphus
      nannodes), a subspecies native to California that underwent an extreme genetic
      bottleneck in the late 1800s.  The genome was generated from Illumina HiSeq 3000
      whole genome sequencing of four individuals, resulting in the assembly of 2.395
      billion base pairs (Gbp) over 602,862 contigs over 500 bp and N50 = 6,885 bp.
      This genome provides a resource to facilitate future genomic research on elk and
      other cervids.

PMID- 29333236
TI  - In silico analysis of natural compounds targeting structural and nonstructural
      proteins of chikungunya virus.
AB  - Background: Chikungunya fever presents as a high-grade fever during its acute
      febrile phase and can be prolonged for months as chronic arthritis in affected
      individuals. Currently, there are no effective drugs or vaccines against this
      virus. The present study was undertaken to evaluate protein-ligand interactions
      of all chikungunya virus (CHIKV) proteins with natural compounds from a MolBase
      library in order to identify potential inhibitors of CHIKV. Methods: Virtual
      screening of the natural compound library against four non-structural and five
      structural proteins of CHIKV was performed. Homology models of the viral proteins
      with unknown structures were created and energy minimized by molecular dynamic
      simulations. Molecular docking was performed to identify the potential inhibitors
      for CHIKV. The absorption, distribution, metabolism and excretion (ADME) toxicity
      parameters for the potential inhibitors were predicted for further prioritization
      of the compounds. Results: Our analysis predicted three compounds, Catechin-5-O
      gallate, Rosmarinic acid and Arjungenin, to interact with CHIKV proteins; two
      (Catechin-5-O-gallate and Rosmarinic acid) with capsid protein, and one
      (Arjungenin) with the E3. Conclusion: The compounds identified show promise as
      potential antivirals, but further in vitro studies are required to test their
      efficacy against CHIKV.

PMID- 29333238
TI  - A method to estimate the number of neurons supporting visual orientation
      discrimination in primates.
AB  - In this method article, we show how to estimate of the number of retinal ganglion
      cells (RGC), and the number of lateral genicular nucleus (LGN) and primary visual
      cortex (V1) neurons involved in visual orientation discrimination tasks. We
      reported the results of this calculation in Kanitscheider et al. (2015), where we
      were interested in comparing the number of neurons in the visual periphery versus
      visual cortex for a specific experiment. This calculation allows estimation of
      the information content at different stages of the visual pathway, which can be
      used to assess the efficiency of the computations performed. As these numbers are
      generally not readily available but may be useful to other researchers, we
      explain here in detail how we obtained them. The calculation is straightforward,
      and simply requires combining anatomical and physiological information about the
      macaque visual pathway. Similar information could be used to repeat the
      calculation for other species or modalities.

PMID- 29333239
TI  - The peer review process for awarding funds to international science research
      consortia: a qualitative developmental evaluation.
AB  - Background: Evaluating applications for multi-national, multi-disciplinary, dual
      purpose research consortia is highly complex. There has been little research on
      the peer review process for evaluating grant applications and almost none on how
      applications for multi-national consortia are reviewed. Overseas development
      investments are increasingly being channelled into international science
      consortia to generate high-quality research while simultaneously strengthening
      multi-disciplinary research capacity. We need a better understanding of how such
      decisions are made and their effectiveness. Methods: An award-making institution
      planned to fund 10 UK-Africa research consortia. Over two annual rounds, 34 out
      of 78 eligible applications were shortlisted and reviewed by at least five
      external reviewers before final selections were made by a face-to-face panel. We
      used an innovative approach involving structured, overt observations of award
      making panel meetings and semi-structured interviews with panel members to
      explore how assessment criteria concerning research quality and capacity
      strengthening were applied during the peer review process. Data were coded and
      analysed using pre-designed matrices which incorporated categories relating to
      the assessment criteria. Results: In general the process was rigorous and well
      managed. However, lack of clarity about differential weighting of criteria and
      variations in the panel's understanding of research capacity strengthening
      resulted in some inconsistencies in use of the assessment criteria. Using the
      same panel for both rounds had advantages, in that during the second round
      consensus was achieved more quickly and the panel had increased focus on
      development aspects. Conclusion: Grant assessment panels for such complex
      research applications need to have topic- and context-specific expertise. They
      must also understand research capacity issues and have a flexible but equitable
      and transparent approach. This study has developed and tested an approach for
      evaluating the operation of such panels and has generated lessons that can
      promote coherence and transparency among grant-makers and ultimately make the
      award-making process more effective.

PMID- 29333240
TI  - The use of dexmedetomidine and intravenous acetaminophen for the prevention of
      postoperative delirium in cardiac surgery patients over 60 years of age: a pilot
      study.
AB  - Background: Delirium is associated with many negative health outcomes.
      Postoperative sedation and opioid administration may contribute to delirium. We
      hypothesize that the use of dexmedetomidine and Intravenous acetaminophen (IVA)
      may lead to reduced opioid consumption and decreased incidence of postoperative
      delirium. This pilot study aims to assess feasibility of using dexmedetomidine
      and IVA in cardiac surgical patients, and obtain effect size estimates for
      incidence and duration of delirium. Methods: A total of 12 adult patients >60
      years of age undergoing cardiac surgery were recruited for the study after IRB
      approval and randomized into 4 groups: Propofol only (P), Propofol with IVA
      (P+A), Dexmedetomidine only (D), Dexmedetomidine with IVA (D+A). Preoperative
      baseline cognition and postoperative delirium was assessed daily until discharge.
      The feasibility was assessed by the number of patients who successfully completed
      the study. Results: All patients completed the study protocol successfully. The
      total incidence of delirium in the study population was 42% (5/12):  67% (2/3) in
      the group P, and 67% (2/3) in the group D, 33% (1/3) in  D+A group and 0%(0/3) 
      P+A group. The incidence of delirium was 17% (1/6) in the group receiving IVA
      compared to 67% (4/6) that did not receive IVA. The mean duration of delirium was
      0-1 days. One patient expired after surgery, unrelated to the study protocol. One
      patient in the D group experienced hypotension with systolic blood pressure <90
      mm of Hg. Conclusions: The feasibility of performing a large-scale project is
      ascertained by the study. Patients receiving IVA had lower incidence of delirium
      compared to patients not receiving IVA which suggests that IVA may have a role in
      reducing the incidence of delirium. A prospective randomized, placebo-controlled
      trial will be the next step in investigating the role of dexmedetomidine and IVA
      in reducing the incidence of delirium.

PMID- 29333241
TI  - Developing data interoperability using standards: A wheat community use case.
AB  - In this article, we present a joint effort of the wheat research community, along
      with data and ontology experts, to develop wheat data interoperability
      guidelines. Interoperability is the ability of two or more systems and devices to
      cooperate and exchange data, and interpret that shared information.
      Interoperability is a growing concern to the wheat scientific community, and
      agriculture in general, as the need to interpret the deluge of data obtained
      through high-throughput technologies grows. Agreeing on common data formats,
      metadata, and vocabulary standards is an important step to obtain the required
      data interoperability level in order to add value by encouraging data sharing,
      and subsequently facilitate the extraction of new information from existing and
      new datasets. During a period of more than 18 months, the RDA Wheat Data
      Interoperability Working Group (WDI-WG) surveyed the wheat research community
      about the use of data standards, then discussed and selected a set of
      recommendations based on consensual criteria. The recommendations promote
      standards for data types identified by the wheat research community as the most
      important for the coming years: nucleotide sequence variants, genome annotations,
      phenotypes, germplasm data, gene expression experiments, and physical maps. For
      each of these data types, the guidelines recommend best practices in terms of use
      of data formats, metadata standards and ontologies. In addition to the best
      practices, the guidelines provide examples of tools and implementations that are
      likely to facilitate the adoption of the recommendations. To maximize the
      adoption of the recommendations, the WDI-WG used a community-driven approach that
      involved the wheat research community from the start, took into account their
      needs and practices, and provided them with a framework to keep the
      recommendations up to date. We also report this approach's potential to be
      generalizable to other (agricultural) domains.

PMID- 29333243
TI  - Unexpected results in Chernozem soil respiration while measuring the effect of a
      bio-fertilizer on soil microbial activity.
AB  - The number of studies investigating the effect of bio-fertilizers is increasing
      because of their importance in sustainable agriculture and environmental quality.
      In our experiments, we measured the effect of different fertilizers on soil
      respiration. In the present study, we were looking for the cause of unexpected
      changes in CO2 values while examining Chernozem soil samples. We concluded that
      CO2 oxidizing microbes or methanotrophs may be present in the soil that
      periodically consume CO2 . This is unusual for a sample taken from the upper
      layer of well-ventilated Chernozem soil with optimal moisture content.

PMID- 29333242
TI  - Predictive value of early postoperative IOP and bleb morphology in Mitomycin-C
      augmented trabeculectomy.
AB  - Background: Our aim was to determine the predictive value of postoperative bleb
      morphological features and intraocular pressure (IOP) on the success rate of
      trabeculectomy. Methods: In this prospective interventional case series, we
      analyzed for one year 80 consecutive primary open angle glaucoma patients who
      underwent mitomycin-augmented trabeculectomy. Bleb morphology was scored using
      the Indiana bleb appearance grading scale (IBAGS). Success was defined as IOP
      <=15 mmHg with or without medications at 12 months. We tested for IOP and bleb
      morphological differences between groups, applied a multivariable regression
      analysis and determined the area under the receiver operating characteristic
      curve (AUC). Results: Age and gender were equally distributed (62.3+/-13.1 years,
      P=0.911). IOP of patients with a successful outcome did not differ from
      unsuccessful ones on day 1, 7 and 30 (all P>=0.2). The AUC of IOP at day 1, day 7
      and 30 for predicting a successful outcome was 0.355, 0.452, and 0.80,
      respectively. The AUC for bleb morphology parameters, bleb height, extension, and
      vascularization, on day 14 were 0.368, 0.408, and 0.549, respectively. Values for
      day 30 were 0.428, 0.563, and 0.654. IOP change from day 1 to day 30 was a good
      predictor of failure (AUC=0.838, 95% CI: 0.704 to 0.971) with a change of more
      than 3 mmHg predicting failure with a sensitivity of 82.5% (95% CI: 68 to 91%)
      and a specificity of 87.5% (95% CI: 53 to 98%). Conclusions: The postoperative
      IOP on day 30 had a fair to good accuracy while the bleb features failed to
      predict a successful outcome. An IOP increase by as little as more than 3 mmHg
      during the first 30 days was a good predictor of failure.

PMID- 29333244
TI  - Piscine birnavirus triggers antiviral immune response in trout red blood cells,
      despite not being infective.
AB  - Background: Some fish viruses, such as piscine orthoreovirus and infectious
      salmon anemia virus, target red blood cells (RBCs), highly replicate inside them
      and induce an immune response. However, the implications of RBCs in the context
      of birnavirus infection (i.e, infectious pancreatic necrosis virus (IPNV)) have
      not yet been studied. Methods:Ex vivo trout RBCs were obtained from peripheral
      blood, ficoll purified and exposed to IPNV in order to analyze infectivity and
      induced immune response using RT-qPCR, immune fluorescence imaging, flow
      cytometry and western-blotting techniques. Results: IPNV could not infect RBCs;
      however, IPNV-exposed RBCs increased the expression of the INF1-related genes ifn
      1, pkr and mx genes. Moreover, conditioned media from IPNV-exposed RBCs conferred
      protection against IPNV infection in CHSE-214 fish cell line. Conclusions: Trout
      RBCs could trigger an antiviral immune response against IPNV infection despite
      not being infected. Fish RBCs could be considered mediators of the antiviral
      response and therefore targets of novel DNA vaccines and new strategies against
      fish viral infections. Further research is ongoing to completely understand the
      molecular mechanism that triggers this immune response in trout RBCs.

PMID- 29333245
TI  - The impact of fresh gas flow on wash-in, wash-out time and gas consumption for
      sevoflurane and desflurane, comparing two anaesthesia machines, a test-lung
      study.
AB  - Low-flow anaesthesia is considered beneficial for the patient and the
      environment, and it is cost reducing due to reduced anaesthetic gas consumption.
      An initial high-flow to saturate the circle system ( wash-in) is desirable from a
      clinical point of view. We measured the wash-in and wash-out times (time to
      saturate and to eliminate the anaesthetic agent, AA), for sevoflurane and
      desflurane, in a test-lung with fixed 3 MAC vaporizer setting at different fresh
      gas flow (FGF) and calculated the consumption of AA. We tried to find an optimal
      flow rate for speed and gas consumption, comparing two anaesthesia machines
      (AMs): Aisys and Flow-i. Time to reach 1 minimal alveolar concentration (MAC)
      (wash-in) decreased (p<0.05) at higher flow rates (1 - 2 - 4) but plateaued at 4
      4.8 l/min. The consumption of AA was at its lowest around 4-4.8 l/min (optimal
      flow) for all but the Aisys /desflurane group. Wash-out times decreased as FGF
      increased, until reaching plateau at FGF of 4-6 l/min. Aisys had generally
      shorter wash-in times at flow rates < 4 l/min as well as lower consumption of AA.
      At higher flow rates there were little difference between the AMs. The "optimal
      FGF" for wash-out, elimination of gas from the test-lung and circle system,
      plateaued with no increase in speed beyond 6 l/min. A fresh gas flow of 4 l/min.
      seems "optimal" taking speed to reach a 1 MAC ET and gas consumption into account
      during wash-in with a fixed 3 MAC vaporizer setting, and increasing fresh gas
      flow beyond 6 l/min does not seem to confirm major benefit during wash-out.

PMID- 29333246
TI  - Easy and efficient ensemble gene set testing with EGSEA.
AB  - Gene set enrichment analysis is a popular approach for prioritising the
      biological processes perturbed in genomic datasets. The Bioconductor project
      hosts over 80 software packages capable of gene set analysis. Most of these
      packages search for enriched signatures amongst differentially regulated genes to
      reveal higher level biological themes that may be missed when focusing only on
      evidence from individual genes. With so many different methods on offer, choosing
      the best algorithm and visualization approach can be challenging. The EGSEA
      package solves this problem by combining results from up to 12 prominent gene set
      testing algorithms to obtain a consensus ranking of biologically relevant
      results.This workflow demonstrates how EGSEA can extend limma-based differential
      expression analyses for RNA-seq and microarray data using experiments that
      profile 3 distinct cell populations important for studying the origins of breast
      cancer. Following data normalization and set-up of an appropriate linear model
      for differential expression analysis, EGSEA builds gene signature specific
      indexes that link a wide range of mouse or human gene set collections obtained
      from MSigDB, GeneSetDB and KEGG to the gene expression data being investigated.
      EGSEA is then configured and the ensemble enrichment analysis run, returning an
      object that can be queried using several S4 methods for ranking gene sets and
      visualizing results via heatmaps, KEGG pathway views, GO graphs, scatter plots
      and bar plots. Finally, an HTML report that combines these displays can fast
      track the sharing of results with collaborators, and thus expedite downstream
      biological validation. EGSEA is simple to use and can be easily integrated with
      existing gene expression analysis pipelines for both human and mouse data.

PMID- 29333247
TI  - Differential methylation analysis of reduced representation bisulfite sequencing
      experiments using edgeR.
AB  - Studies in epigenetics have shown that DNA methylation is a key factor in
      regulating gene expression. Aberrant DNA methylation is often associated with DNA
      instability, which could lead to development of diseases such as cancer. DNA
      methylation typically occurs in CpG context. When located in a gene promoter, DNA
      methylation often acts to repress transcription and gene expression. The most
      commonly used technology of studying DNA methylation is bisulfite sequencing (BS
      seq), which can be used to measure genomewide methylation levels on the single
      nucleotide scale. Notably, BS-seq can also be combined with enrichment
      strategies, such as reduced representation bisulfite sequencing (RRBS), to target
      CpG-rich regions in order to save per-sample costs. A typical DNA methylation
      analysis involves identifying differentially methylated regions (DMRs) between
      different experimental conditions. Many statistical methods have been developed
      for finding DMRs in BS-seq data. In this workflow, we propose a novel approach of
      detecting DMRs using edgeR. By providing a complete analysis of RRBS profiles of
      epithelial populations in the mouse mammary gland, we will demonstrate that
      differential methylation analyses can be fit into the existing pipelines
      specifically designed for RNA-seq differential expression studies. In addition,
      the edgeR generalized linear model framework offers great flexibilities for
      complex experimental design, while still accounting for the biological
      variability. The analysis approach illustrated in this article can be applied to
      any BS-seq data that includes some replication, but it is especially appropriate
      for RRBS data with small numbers of biological replicates.

PMID- 29333248
TI  - Out-of-pocket health expenditure and fairness in utilization of health care
      facilities in Cambodia in 2005 and 2010.
AB  - Background: Out-of-pocket (OOP) payments for health care are highly pervasive in
      several low-and-middle income countries. The Cambodian health system has
      envisaged massive repositioning of various health care financing to ensure
      equitable access to health care. This analysis examines catastrophic, economic,
      as well as fairness, impacts of OOP health care payments on households in
      Cambodia over time. Methods: Data from two waves of a nationally representative
      household survey conducted in Cambodia (CDHS Surveys 2005 and 2010) were
      utilized. Healthcare utilizations based on economic status were compared during
      2005 and 2010. Variables of interests were i) where care was sought and the
      instances of treatments, i.e. was treatment sought the first, second or third
      time; (ii) the mode of payment for treatment of the respondent or for any
      household member due to sickness or injury in the last 30 days prior to the
      survey period. Lorenz curves were applied to assess the degree of distribution of
      inequality in OOP expenditures between different income brackets. Results: The
      findings revealed that there was inequality and unfairness in health care
      payments, and catastrophic spending is more common among the poor in Cambodia.
      The majority of people from poorer households experienced economic hardship and
      have taken to catastrophic health care spending through sales of personal
      possessions.  Conclusion: Based on the findings from this analysis, more
      attention is needed on effective financial protection for Cambodians to promote
      fairness. The government should increase spending on services being provided at
      public health care facilities to reduce ever increasing reliance on private
      sector providers. These approaches would go a long way to reduce the economic
      burden of care utilization among the poorest.

PMID- 29333249
TI  - Health Technology Assessment capacity development in low- and middle-income
      countries: Experiences from the international units of HITAP and NICE.
AB  - Health Technology Assessment (HTA) is policy research that aims to inform
      priority setting and resource allocation. HTA is increasingly recognized as a
      useful policy tool in low- and middle-income countries (LMICs), where there is a
      substantial need for evidence to guide Universal Health Coverage policies, such
      as benefit coverage, quality improvement interventions and quality standards, all
      of which aim at improving the efficiency and equity of the healthcare system. The
      Health Intervention and Technology Assessment Program (HITAP), Thailand, and the
      National Institute for Health and Care Excellence (NICE), UK, are national HTA
      organizations providing technical support to governments in LMICs to build up
      their priority setting capacity. This paper draws lessons from their capacity
      building programs in India, Colombia, Myanmar, the Philippines, and Vietnam. Such
      experiences suggest that it is not only technical capacity, for example
      analytical techniques for conducting economic evaluation, but also management,
      coordination and communication capacity that support the generation and use of
      HTA evidence in the respective settings. The learned lessons may help guide the
      development of HTA capacity in other LMICs.

PMID- 29333250
TI  - Retract p < 0.005 and propose using JASP, instead.
AB  - Seeking to address the lack of research reproducibility in science, including
      psychology and the life sciences, a pragmatic solution has been raised recently: 
      to use a stricter p < 0.005 standard for statistical significance when claiming
      evidence of new discoveries. Notwithstanding its potential impact, the proposal
      has motivated a large mass of authors to dispute it from different philosophical
      and methodological angles. This article reflects on the original argument and the
      consequent counterarguments, and concludes with a simpler and better-suited
      alternative that the authors of the proposal knew about and, perhaps, should have
      made from their Jeffresian perspective: to use a Bayes factors analysis in
      parallel (e.g., via JASP) in order to learn more about frequentist error
      statistics and about Bayesian prior and posterior beliefs without having to mix
      inconsistent research philosophies.

PMID- 29333251
TI  - Can circulating tumor DNA be used for direct and early stage cancer detection?
AB  - In the August 16th issue of Science Translational Medicine, Phallen et al propose
      a method for early cancer diagnosis by using circulating tumor DNA (1). One major
      advance of this paper includes optimized sequencing of cell-free/circulating
      tumor DNA (ctDNA) without knowledge of tumor mutations. Evaluation of 200
      patients with colorectal, breast, lung and ovarian cancer revealed mutations in
      ctDNA in approx. 60-70% of all patients, including stage 1 and stage 2 disease.
      If this data can be reproduced in asymptomatic individuals, they will likely have
      a major impact on early cancer detection and patient outcomes. In this
      commentary, we examine the feasibility of this approach for detecting small,
      asymptomatic tumors, based on previously published empirical data.

PMID- 29333252
TI  - Recent advances in pharmacological management of urinary incontinence.
AB  - Lower urinary tract symptoms-in particular, storage disorders (for example,
      urinary incontinence) as well as bladder underactivity-are major health-related
      problems that increase with age. Yet lower urinary tract symptoms remain under
      diagnosed and poorly managed, and incontinence has been cited as the major reason
      for institutionalization in elderly populations and is one of the most common
      conditions in primary care practice. Although lifestyle and behavior therapy has
      been used as a useful treatment regimen for urge incontinence, medications (often
      used as adjunct) can provide additional benefit. This review will include current
      therapies used for treatment of urinary incontinence.

PMID- 29333253
TI  - The stress concept in gastroenterology: from Selye to today.
AB  - More than eighty years after Hans Selye (1907-1982) first developed a concept
      describing how different types of environmental stressors affect physiological
      functions and promote disease development (called the "general adaptation
      syndrome") in 1936, we herein review advances in theoretical, mechanistic, and
      clinical knowledge in stress research, especially in the area of
      gastroenterology, and summarize progress and future perspectives arising from an
      interdisciplinary psychoneurobiological framework in which genetics, epigenetics,
      and other advanced ( omics) technologies in the last decade continue to refine
      knowledge about how stress affects the brain-gut axis in health and
      gastrointestinal disease. We demonstrate that neurobiological stress research
      continues to be a driving force for scientific progress in gastroenterology and
      related clinical areas, inspiring translational research from animal models to
      clinical applications, while highlighting some areas that remain incompletely
      understood, such as the roles of sex/gender and gut microbiota in health and
      disease. Future directions of research should include not only the genetics of
      the stress response and resilience but also epigenetic contributions.

PMID- 29333254
TI  - Better understanding of childhood asthma, towards primary prevention - are we
      there yet? Consideration of pertinent literature.
AB  - Asthma is a chronic disease, characterized by reversible airway obstruction,
      airway inflammation and hyper-reactivity. The prevalence of asthma has risen
      dramatically over the past decade, affecting around 300,000,000 people. The
      etiology is multifactorial, with genetic, epigenetic, developmental and
      environmental factors playing a role. A complex interaction between the
      intrauterine environment, the developing immune system, the infant's microbiome
      and infectious organisms may lead to the development of allergic sensitization
      and asthma. Thus, a large number of studies have investigated the risk factors
      for childhood asthma, with a meticulous search of modifiable factors that could
      aid in primary prevention. We present a current literature review from 2014-2017,
      as well as older classic publications, on the pathogenesis and the potential
      modifiable factors for primary prevention of asthma. No ideal preventive measure
      has yet been found. Rather, creating favorable prenatal and postnatal
      environments, minimal exposure to hostile environmental factors, prevention of
      infections in early life, allergic desensitization and nutritional modifications
      could possibly reduce asthma inception. In the era of personalized medicine,
      identifying individual risk factors and tailoring specific preventive measures is
      warranted.

PMID- 29333256
TI  - Pathophysiology and treatment of patients with beta-thalassemia - an update.
AB  - Thalassemia (thal) is an autosomal recessive, hereditary, chronic hemolytic
      anemia due to a partial or complete deficiency in the synthesis of alpha-globin
      chains (alpha-thal) or beta-globin chains (beta-thal) that compose the major
      adult hemoglobin (alpha 2beta 2). It is caused by one or more mutations in the
      corresponding genes. The unpaired globin chains are unstable; they precipitate
      intracellularly, resulting in hemolysis, premature destruction of red blood cell
      [RBC] precursors in the bone marrow, and a short life-span of mature RBCs in the
      circulation. The state of anemia is treated by frequent RBC transfusions. This
      therapy results in the accumulation of iron (iron overload), a condition that is
      exacerbated by the breakdown products of hemoglobin (heme and iron) and the
      increased iron uptake for the chronic accelerated, but ineffective, RBC
      production. Iron catalyzes the generation of reactive oxygen species, which in
      excess are toxic, causing damage to vital organs such as the heart and liver and
      the endocrine system. Herein, we review recent findings regarding the
      pathophysiology underlying the major symptoms of beta-thal and potential
      therapeutic modalities for the amelioration of its complications, as well as new
      modalities that may provide a cure for the disease.

PMID- 29333257
TI  - Recent advances on gradient hydrogels in biomimetic cartilage tissue engineering.
AB  - Articular cartilage (AC) is a seemingly simple tissue that has only one type of
      constituting cell and no blood vessels and nerves. In the early days of tissue
      engineering, cartilage appeared to be an easy and promising target for
      reconstruction and this was especially motivating because of widespread AC
      pathologies such as osteoarthritis and frequent sports-induced injuries. However,
      AC has proven to be anything but simple. Recreating the varying properties of its
      zonal structure is a challenge that has not yet been fully answered. This caused
      the shift in tissue engineering strategies toward bioinspired or biomimetic
      approaches that attempt to mimic and simulate as much as possible the structure
      and function of the native tissues. Hydrogels, particularly gradient hydrogels,
      have shown great potential as components of the biomimetic engineering of the
      cartilaginous tissue.

PMID- 29333255
TI  - In vivo genome editing in animals using AAV-CRISPR system: applications to
      translational research of human disease.
AB  - Adeno-associated virus (AAV) has shown promising therapeutic efficacy with a good
      safety profile in a wide range of animal models and human clinical trials. With
      the advent of clustered regulatory interspaced short palindromic repeat (CRISPR)
      based genome-editing technologies, AAV provides one of the most suitable viral
      vectors to package, deliver, and express CRISPR components for targeted gene
      editing. Recent discoveries of smaller Cas9 orthologues have enabled the
      packaging of Cas9 nuclease and its chimeric guide RNA into a single AAV delivery
      vehicle for robust in vivo genome editing. Here, we discuss how the combined use
      of small Cas9 orthologues, tissue-specific minimal promoters, AAV serotypes, and
      different routes of administration has advanced the development of efficient and
      precise in vivo genome editing and comprehensively review the various AAV-CRISPR
      systems that have been effectively used in animals. We then discuss the clinical
      implications and potential strategies to overcome off-target effects,
      immunogenicity, and toxicity associated with CRISPR components and AAV delivery
      vehicles. Finally, we discuss ongoing non-viral-based ex vivo gene therapy
      clinical trials to underscore the current challenges and future prospects of
      CRISPR/Cas9 delivery for human therapeutics.

PMID- 29333258
TI  - An RNA decay factor wears a new coat: UPF3B modulates translation termination.
AB  - Nonsense-mediated RNA decay (NMD) is a highly conserved and selective RNA
      turnover pathway that has been subject to intense scrutiny. NMD identifies and
      degrades subsets of normal RNAs, as well as abnormal mRNAs containing premature
      termination codons. A core factor in this pathway-UPF3B-is an adaptor protein
      that serves as an NMD amplifier and an NMD branch-specific factor. UPF3B is
      encoded by an X-linked gene that when mutated causes intellectual disability and
      is associated with neurodevelopmental disorders, including schizophrenia and
      autism. Neu-Yilik et al. now report a new function for UPF3B: it modulates
      translation termination. Using a fully reconstituted in vitro translation system,
      they find that UPF3B has two roles in translation termination. First, UPF3B
      delays translation termination under conditions that mimic premature translation
      termination. This could drive more efficient RNA decay by allowing more time for
      the formation of RNA decay-stimulating complexes. Second, UPF3B promotes the
      dissociation of post-termination ribosomal complexes that lack nascent peptide.
      This implies that UPF3B could promote ribosome recycling. Importantly, the
      authors found that UPF3B directly interacts with both RNA and the factors that
      recognize stop codons-eukaryotic release factors (eRFs)-suggesting that UPF3B
      serves as a direct regulator of translation termination. In contrast, a NMD
      factor previously thought to have a central regulatory role in translation
      termination-the RNA helicase UPF1-was found to indirectly interact with eRFs and
      appears to act exclusively in post-translation termination events, such as RNA
      decay, at least in vitro. The finding that an RNA decay-promoting factor, UFP3B,
      modulates translation termination has many implications. For example, the ability
      of UPF3B to influence the development and function of the central nervous system
      may be not only through its ability to degrade specific RNAs but also through its
      impact on translation termination and subsequent events, such as ribosome
      recycling.

PMID- 29333259
TI  - Predictors of outcome in phaeochromocytomas and paragangliomas.
AB  - Phaeochromocytomas and paragangliomas (PPGLs) are catecholamine-secreting
      neuroendocrine tumours characterised by high rates of heritability and genetic
      heterogeneity. Despite advances in the genetic diagnosis and improved
      understanding of the molecular aberrations underlying these tumours, predictive
      markers of malignancy remain scarce, limiting the outlook of patients with
      metastatic PPGL. The identification of robust predictive markers remains the most
      pressing challenge in PPGL management, so that the potential of targeted therapy
      to impact patient care can be fully realised.

PMID- 29333261
TI  - Sleep apnea and its role in transportation safety.
AB  - Obstructive sleep apnea (OSA) is a main cause of excessive daytime sleepiness and
      increases the risk for driving accidents, which can be normalized by treatment
      with continuous positive airway pressure ventilation. Since it is estimated that
      OSA is not diagnosed in about 80% of cases, recognition of patients at risk for
      driving accidents is a problem from both medical and societal points of view.
      Strategies to screen and identify subjects at high risk for driving accidents are
      under study in order to improve safety on the road, especially for commercial
      drivers, who show a high prevalence of OSA.

PMID- 29333260
TI  - Use of electroanalgesia and laser therapies as alternatives to opioids for acute
      and chronic pain management.
AB  - The use of opioid analgesics for postoperative pain management has contributed to
      the global opioid epidemic. It was recently reported that prescription opioid
      analgesic use often continued after major joint replacement surgery even though
      patients were no longer experiencing joint pain. The use of epidural local
      analgesia for perioperative pain management was not found to be protective
      against persistent opioid use in a large cohort of opioid-naive patients
      undergoing abdominal surgery. In a retrospective study involving over 390,000
      outpatients more than 66 years of age who underwent minor ambulatory surgery
      procedures, patients receiving a prescription opioid analgesic within 7 days of
      discharge were 44% more likely to continue using opioids 1 year after surgery. In
      a review of 11 million patients undergoing elective surgery from 2002 to 2011,
      both opioid overdoses and opioid dependence were found to be increasing over
      time. Opioid-dependent surgical patients were more likely to experience
      postoperative pulmonary complications, require longer hospital stays, and
      increase costs to the health-care system. The Centers for Disease Control and
      Prevention emphasized the importance of finding alternatives to opioid medication
      for treating pain. In the new clinical practice guidelines for back pain, the
      authors endorsed the use of non-pharmacologic therapies. However, one of the more
      widely used non-pharmacologic treatments for chronic pain (namely radiofrequency
      ablation therapy) was recently reported to have no clinical benefit. Therefore,
      this clinical commentary will review evidence in the peer-reviewed literature
      supporting the use of electroanalgesia and laser therapies for treating acute
      pain, cervical (neck) pain, low back pain, persistent post-surgical pain after
      spine surgery ("failed back syndrome"), major joint replacements, and abdominal
      surgery as well as other common chronic pain syndromes (for example, myofascial
      pain, peripheral neuropathic pain, fibromyalgia, degenerative joint
      disease/osteoarthritis, and migraine headaches).

PMID- 29333262
TI  - Recent advances in the biology and therapy of medullary thyroid carcinoma.
AB  - Medullary thyroid cancer (MTC) is a relatively uncommon yet prognostically
      significant thyroid cancer. Several recent advances in the biology and current or
      potential treatment of MTC are notable. These include a new understanding of the
      developmental biology of the thyroid C cell, which heretofore was thought to
      develop from the neural crest. RET, encoded by the most common driver gene in
      MTC, has been shown to be a dual function kinase, thus expanding its potential
      substrate repertoire. Promising new therapeutic developments are occurring; many
      have recently progressed to clinical development. There are new insights into RET
      inhibitor therapy for MTC. New strategies are being developed to inhibit the RAS
      proteins, which are potential therapeutic targets in MTC. Potential emerging
      immunotherapies for MTC are discussed. However, gaps in our knowledge of the
      basic biology of the C cell, its transformation to MTC, and the mechanisms of
      resistance to therapy impede progress; further research in these areas would have
      a substantial impact on the field.

PMID- 29333264
TI  - How anthropogenic shifts in plant community composition alter soil food webs.
AB  - There are great concerns about the impacts of soil biodiversity loss on ecosystem
      functions and services such as nutrient cycling, food production, and carbon
      storage. A diverse community of soil organisms that together comprise a complex
      food web mediates such ecosystem functions and services. Recent advances have
      shed light on the key drivers of soil food web structure, but a conceptual
      integration is lacking. Here, we explore how human-induced changes in plant
      community composition influence soil food webs. We present a framework describing
      the mechanistic underpinnings of how shifts in plant litter and root traits and
      microclimatic variables impact on the diversity, structure, and function of the
      soil food web. We then illustrate our framework by discussing how shifts in plant
      communities resulting from land-use change, climatic change, and species
      invasions affect soil food web structure and functioning. We argue that
      unravelling the mechanistic links between plant community trait composition and
      soil food webs is essential to understanding the cascading effects of
      anthropogenic shifts in plant communities on ecosystem functions and services.

PMID- 29333265
TI  - The Effects of a Home-based Intervention Conducted by College Students for Young
      Children with Developmental Delays in Vietnam.
AB  - Objectives: The project assessed the efficacy of a home-based intervention
      program for young children (n= 64, ages ranging from 3-6 years) with
      developmental delays in Vietnam. It was hypothesized that the children in the
      intervention group would show greater progress in adaptive behavior than the
      children in the control group. Methods: Assessment of the program efficacy was
      carried out by comparing children who received services for 6 months and those
      who did not. Children who were recognized as having developmental delays by
      teachers in kindergarten programs, and confirmed by trained evaluators based on
      the Vineland Adaptive Behavior Scale-II (VABS-II), were randomly assigned to
      intervention and control groups. Twenty student teachers were recruited from a
      teaching university and were provided with pre-program training and ongoing
      supervision. Results: The outcomes of the program were examined at 0, 3, and 6
      months using the VABS-II. The intervention group improved significantly more than
      the control group in overall adaptive functioning and in the areas of
      communication, social skills and motor skills. Conclusion: The project is one of
      only a few early intervention projects to apply randomized control trials in a
      low-middle-income country. The results demonstrate the feasibility of carrying
      out the intervention program using teachers with no prior experience of working
      with children with delays/disabilities, where professional resources are scarce
      for this population.

PMID- 29333266
TI  - Evaluation of a Health Education Intervention to Improve Knowledge, Skills,
      Behavioral Intentions and Resources Associated with Preventable Determinants of
      Infant Mortality.
AB  - Mississippi has the highest rate of infant mortality in the nation (9.3 infant
      deaths for 1,000 live births). A health disparity exists between white infants
      (6.2) and black infants (13.0). This project reports on the effectiveness of a
      pilot educational program, Healthy Moms and Healthy Babies, which sought to
      improve knowledge, skills, behavioral intentions and resources related to
      preventable determinants of infant mortality. A curriculum was developed and
      piloted with women who were currently pregnant, thinking of becoming pregnant or
      who had an infant <1 year old. Local Head Start Centers offered recruiting
      assistance and meeting space for the sessions. Six content areas were developed
      which addressed pre- and postnatal nutrition and physical activity, smoking,
      breastfeeding, maternal mental health and safe infant sleep. Sixteen objectives
      were evaluated to determine intervention effectiveness. Participants were very
      satisfied with the program overall. Fourteen of sixteen objectives were met.
      Unmet objectives were gaining the skill of interpreting a nutritional label
      (Objective 75.0%, Observed 71.4%) and being able to name five health benefits of
      breastfeeding (Objective 85.0%, Observed 81.0%). Future programs will incorporate
      participant feedback which included allowing more time to learn about
      interpreting food labels and addressing financial stress. Reducing preterm birth
      is a national public health priority. Addressing knowledge gaps through risk
      reduction education may reduce behaviors associated with determinants of infant
      mortality such as low birth weight and preterm birth. Head Start Centers are
      convenient locations that can serve as hubs of education for the entire family.
      Addressing knowledge gaps through risk-reduction education and providing adequate
      resources for smoking cessation and lactation support may increase knowledge and
      skills and reduce behaviors associated with determinants of infant mortality such
      as low birth weight and preterm birth.

PMID- 29333263
TI  - Vancomycin-resistant enterococcus infection in the hematopoietic stem cell
      transplant recipient: an overview of epidemiology, management, and prevention.
AB  - Vancomycin-resistant enterococcus (VRE) is now one of the leading causes of
      nosocomial infections in the United States. Hematopoietic stem cell
      transplantation (HSCT) recipients are at increased risk of VRE colonization and
      infection. VRE has emerged as a major cause of bacteremia in this population,
      raising important clinical questions regarding the role and impact of VRE
      colonization and infection in HSCT outcomes as well as the optimal means of
      prevention and treatment. We review here the published literature and scientific
      advances addressing these thorny issues and provide a rational framework for
      their approach.

PMID- 29333267
TI  - Type 1 diabetes genome-wide association studies: not to be lost in translation.
AB  - Genetic studies have identified >60 loci associated with the risk of developing
      type 1 diabetes (T1D). The vast majority of these are identified by genome-wide
      association studies (GWAS) using large case-control cohorts of European ancestry.
      More than 80% of the heritability of T1D can be explained by GWAS data in this
      population group. However, with few exceptions, their individual contribution to
      T1D risk is low and understanding their function in disease biology remains a
      huge challenge. GWAS on its own does not inform us in detail on disease
      mechanisms, but the combination of GWAS data with other omics-data is beginning
      to advance our understanding of T1D etiology and pathogenesis. Current knowledge
      supports the notion that genetic variation in both pancreatic beta cells and in
      immune cells is central in mediating T1D risk. Advances, perspectives and
      limitations of GWAS are discussed in this review.

PMID- 29333269
TI  - The immune system of the liver: 50 years of strangeness.

PMID- 29333268
TI  - Progress of genome-wide association studies of ankylosing spondylitis.
AB  - Ankylosing spondylitis (AS) is an immune-mediated arthritis which primarily
      affects the spine and sacroiliac joints. Significant progress has been made in
      discovery of genetic associations with AS by genome-wide association studies
      (GWAS) over past decade. These findings have uncovered novel pathways involved
      pathogenesis of the disease and have led to introduction of novel therapeutic
      treatments for AS. In this Review, we discuss the genetic variations associated
      with AS identified by GWAS, the major pathways revealed by these AS-associated
      variations and critical cell types involved in AS development.

PMID- 29333271
TI  - Childhood asthma prevalence: cross-sectional record linkage study comparing
      parent-reported wheeze with general practitioner-recorded asthma diagnoses from
      primary care electronic health records in Wales.
AB  - Introduction: Electronic health records (EHRs) are increasingly used to estimate
      the prevalence of childhood asthma. The relation of these estimates to those
      obtained from parent-reported wheezing suggestive of asthma is unclear. We
      hypothesised that parent-reported wheezing would be more prevalent than general
      practitioner (GP)-recorded asthma diagnoses in preschool-aged children. Methods:
      1529 of 1840 (83%) Millennium Cohort Study children registered with GPs in the
      Welsh Secure Anonymised Information Linkage databank were linked. Prevalences of
      parent-reported wheezing and GP-recorded asthma diagnoses in the previous 12
      months were estimated, respectively, from parent report at ages 3, 5, 7 and 11
      years, and from Read codes for asthma diagnoses and prescriptions based on GP
      EHRs over the same time period. Prevalences were weighted to account for
      clustered survey design and non-response. Cohen's kappa statistics were used to
      assess agreement. Results: Parent-reported wheezing was more prevalent than GP
      recorded asthma diagnoses at 3 and 5 years. Both diminished with age: by age 11,
      prevalences of parent-reported wheezing and GP-recorded asthma diagnosis were
      12.9% (95% CI 10.6 to 15.4) and 10.9% (8.8 to 13.3), respectively (difference: 2%
      (-0.5 to 4.5)). Other GP-recorded respiratory diagnoses accounted for 45.7% (95%
      CI 37.7 to 53.9) and 44.8% (33.9 to 56.2) of the excess in parent-reported
      wheezing at ages 3 and 5 years, respectively. Conclusion: Parent-reported
      wheezing is more prevalent than GP-recorded asthma diagnoses in the preschool
      years, and this difference diminishes in primary school-aged children. Further
      research is needed to evaluate the implications of these differences for the
      characterisation of longitudinal childhood asthma phenotypes from EHRs.

PMID- 29333270
TI  - Lessons from ten years of genome-wide association studies of asthma.
AB  - Twenty-five genome-wide association studies (GWAS) of asthma were published
      between 2007 and 2016, the largest with a sample size of 157242 individuals.
      Across these studies, 39 genetic variants in low linkage disequilibrium (LD) with
      each other were reported to associate with disease risk at a significance
      threshold of P<5 * 10-8, including 31 in populations of European ancestry.
      Results from analyses of the UK Biobank data (n=380 503) indicate that at least
      28 of the 31 associations reported in Europeans represent true-positive findings,
      collectively explaining 2.5% of the variation in disease liability (median of
      0.06% per variant). We identified 49 transcripts as likely target genes of the
      published asthma risk variants, mostly based on LD with expression quantitative
      trait loci (eQTL). Of these genes, 16 were previously implicated in disease
      pathophysiology by functional studies, including TSLP, TNFSF4, ADORA1, CHIT1 and
      USF1. In contrast, at present, there is limited or no functional evidence
      directly implicating the remaining 33 likely target genes in asthma
      pathophysiology. Some of these genes have a known function that is relevant to
      allergic disease, including F11R, CD247, PGAP3, AAGAB, CAMK4 and PEX14, and so
      could be prioritized for functional follow-up. We conclude by highlighting three
      areas of research that are essential to help translate GWAS findings into
      clinical research or practice, namely validation of target gene predictions,
      understanding target gene function and their role in disease pathophysiology and
      genomics-guided prioritization of targets for drug development.

PMID- 29333272
TI  - Peracetic acid disinfection kinetics for combined sewer overflows: indicator
      organisms, antibiotic resistance genes, and microbial community.
AB  - Combined sewer overflows (CSOs) degrade water quality and end-of-pipe treatment
      is one potential solution for retrofitting this outdated infrastructure. The goal
      of this research was to evaluate peracetic acid (PAA) as a disinfectant for CSOs
      using viability based molecular methods for antibiotic resistance genes (ARGs),
      indicator organism marker gene BacHum, and 16S rRNA genes. Simulated CSO effluent
      was prepared using 23-40% wastewater, representing the higher end of the range of
      wastewater concentrations reported in CSO effluent. PAA residual following
      disinfection was greatest for samples with the lowest initial COD. Treatment of
      simulated CSO effluent (23% wastewater) with 100 mg?min/L PAA (5 mg/L PAA, 20
      min) was needed to reduce viable cell sul1, tet(G), and BacHum (1.0+/-0.63-3.2+/
      0.25-log) while 25 to 50 mg*min/L PAA (5 mg/L PAA, 5-10 min) was needed to reduce
      viable cell loads (0.62+/-0.56-1.6+/-0.08-log) in 40% wastewater from a different
      municipal treatment plant. Increasing contact time after the initial decrease in
      viable cell gene copies did not significantly improve treatment. A much greater
      applied Ct of 1200 mg?min/L PAA (20 mg/L PAA, 60 min) was required for
      significant log reduction of 16S rRNA genes (3.29+/-0.13-log). No significant
      losses of mexB were observed during the study. Data were fitted to a Chick-Watson
      model and resulting inactivation constants for sul1 and tet(G) > BacHum > 16S
      rRNA. Amplicon sequencing of the 16S rRNA gene indicated the initial viable and
      total microbial communities were distinct and that treatment with PAA resulted in
      marked increases of the relative abundance of select phyla, particularly
      Clostridia which increased by 1-1.5 orders of magnitude. Results confirm that
      membrane disruption is a mechanism for PAA disinfection and further treatment is
      needed to reduce total ARGs in CSO effluent.

PMID- 29333273
TI  - Changes in androstenedione, dehydroepiandrosterone, testosterone, estradiol, and
      estrone over the menopausal transition.
AB  - Background: Previous reports have noted that dehydroepiandrosterone-sulfate
      (DHEAS) increases prior to the final menstrual period (FMP) and remains stable
      beyond the FMP. How DHEAS concentrations correspond with other sex hormones
      across the menopausal transition (MT) including androstenedione (A4),
      testosterone (T), estrone (E1), and estradiol (E2) is not known. Our objective
      was to examine how DHEAS, A4, T, E1, and E2 changed across the MT by White vs.
      African-American (AA) race/ethnicity. Methods: We conducted a longitudinal
      observational analysis of a subgroup of women from the Study of Women's Health
      Across the Nation observed over 4 visits prior to and 4 visits after the FMP (n =
      110 women over 9 years for 990 observations). The main outcome measures were
      DHEAS, A4, T, E1, and E2. Results: Compared to the decline in E2 concentrations,
      androgen concentrations declined minimally over the MT. T (beta 9.180, p <
      0.0001) and E1 (beta 11.365, p < 0.0001) were higher in Whites than in AAs, while
      elevations in DHEAS (beta 28.80, p = 0.061) and A4 (beta 0.2556, p = 0.052) were
      borderline. Log-transformed E2 was similar between Whites and AAs (beta 0.0764, p
      = 0.272). Body mass index (BMI) was not significantly associated with
      concentrations of androgens or E1 over time. Conclusion: This report suggests
      that the declines in E2 during the 4 years before and after the FMP are
      accompanied by minimal changes in DHEAS, A4, T, and E1. There are modest
      differences between Whites and AAs and minimal differences by BMI.

PMID- 29333274
TI  - Report of an Italian family carrying a typical Indian variant of the Nilgiris
      tribal groups resulting from a de novo occurrence.
AB  - G6PD deficiency is quite common in Italy where it is characterized by extreme
      molecular and biochemical heterogeneity. We report a 15-year-old Italian boy with
      G6PD Nilgiri (c.593G>A, p.Arg198His), a typical Indian variant of the Nilgiris
      tribal groups. Further, this variant was biochemically characterized, and the
      molecular screening of the family highlighted a de novo mutational event. To
      date, this family is the first Caucasian family carrying the G6PD Nilgiri
      variant.

PMID- 29333275
TI  - Barriers to care for chronic hepatitis C in the direct-acting antiviral era: a
      single-centre experience.
AB  - Background: Cure rates for chronic hepatitis C have improved dramatically with
      direct-acting antivirals (DAAs), but treatment barriers remain. We aimed to
      compare treatment initiation rates and barriers across both interferon-based and
      DAA-based eras. Methods: We conducted a retrospective cohort study of all
      patients with chronic hepatitis C seen at an academic hepatology clinic from 1999
      to 2016. Patients were identified to have chronic hepatitis C by the
      International Classification of Diseases, Ninth Revision codes, and the diagnosis
      was validated by chart review. Patients were excluded if they did not have at
      least one visit in hepatology clinic, were under 18 years old or had prior
      treatment with DAA therapy. Patients were placed in the DAA group if they were
      seen after 1 January 2014 and had not yet achieved virological cure with prior
      treatment. All others were considered in the interferon group. Results: 3202
      patients were included (interferon era: n=2688; DAA era: n=514). Despite higher
      rates of decompensated cirrhosis and medical comorbidities in the DAA era,
      treatment and sustained virological response rates increased significantly when
      compared with the interferon era (76.7% vs 22.3%, P<0.001; 88.8% vs 55%, P<0.001,
      respectively). Lack of follow-up remained a significant reason for non-treatment
      in both groups (DAA era=24% and interferon era=45%). An additional 8% of patients
      in the DAA era were not treated due to insurance or issues with cost. In the DAA
      era, African-Americans, compared with Caucasians, had significantly lower odds of
      being treated (OR=0.37, P=0.02). Conclusions: Despite higher rates of medical
      comorbidities in the DAA era, considerable treatment challenges remain including
      cost, loss to follow-up and ethnic disparities.

PMID- 29333276
TI  - Neuropsychiatric performance and treatment of hepatitis C with direct-acting
      antivirals: a prospective study.
AB  - Background: Since direct-acting antivirals (DAAs) have been approved for the
      treatment of hepatitis C virus (HCV) infection, a small series of patients with
      new-onset neuropsychiatric alterations have been referred to us. We therefore set
      out to study neuropsychiatric function in relation to DAAs prospectively.
      Methods: Ten patients with cirrhosis and 12 post-liver transplant (post-LT)
      patients were enrolled. All underwent wake electroencephalography (EEG) and a
      neuropsychological evaluation (paper and pencil battery, simple/choice reaction
      times, working memory task) at baseline, at the end of treatment with DAAs and
      after 6 months. At the same time points, full blood count, liver/kidney function
      tests, quantitative HCV RNA, ammonia and immunosuppressant drug levels were
      obtained, as appropriate. Results: Patients with cirrhosis were significantly
      older than post-LT patients (65+/-12 vs 55+/-7 years; P<0.05). Neuropsychological
      performance and wake EEG were comparable in the two groups at baseline. At the
      end of a course of treatment with DAAs, a significant slowing in choice reaction
      times and in the EEG (increased relative delta power) was observed in patients
      with cirrhosis, which resolved after 6 months. In contrast, no significant
      changes over time were observed in the neuropsychiatric performance of post-LT
      patients. No significant associations were observed between neuropsychiatric
      performance and stand-alone/combined laboratory variables. Conclusion: Some
      degree of neuropsychiatric impairment was observed in relation to treatment with
      DAAs in patients with cirrhosis, but not in post-LT patients, suggesting that the
      former may be sensitive to mild DAA neurotoxicity.

PMID- 29333277
TI  - Familial risks for gallstones in the population of Sweden.
AB  - Objectives: Gallstone disease (cholelithiasis) has a familial component, but
      detailed data on the modification of familial risk are lacking. Using nationwide
      hospital and population records, we aimed to determine detailed familial risks
      for medically diagnosed gallstone disease. Design: Subjects were obtained from
      the Multigeneration Register, which contains family data on the Swedish
      population, and patients with gallstone disease were identified from the Hospital
      Discharge Register (1964-2015) and the Outpatient Register (2001-2015).
      Standardised incidence ratios (SIRs) were calculated as the ratio of observed to
      expected number of cases. Results: Gallstone disease was diagnosed in 660 732
      patients, with an overall incidence of 131 per 100 000 person-years. Familial
      cases accounted for 36.0% of all patients with gallstone disease. Of these, 50.9%
      had a parental family history (SIR 1.62), 35.1% had a sibling history (SIR 1.75)
      and 14.0% had a parental+sibling history (SIR 2.58). Among a total of 54 630
      affected siblings, 84.4% were sibling pairs (SIR 1.55). However, the remaining
      15.6% of the affected siblings constituted the high-risk group of multiple
      affected siblings and an SIR >10; these persons accounted for 7.7% of all
      familial cases. The spousal risk was only slightly increased to 1.18.
      Conclusions: Overall, the results point to the underlying genetic causes for the
      observed familial clustering, which may involve polygenic gene-environmental
      interactions for most familial cases but high-risk genes in close to 10% of
      cases. Family histories should be taken into account in the medical setting and
      used for counselling of at-risk individuals.

PMID- 29333278
TI  - Clinical influence of exercise therapy on sarcopenia in patients with chronic
      pancreatitis: a study protocol for a randomised controlled trial.
AB  - Introduction and purpose: Chronic pancreatitis (CP) involves progressive
      inflammatory changes to the pancreas and can lead to permanent structural damage
      and impairment of both endocrine and exocrine functions. Current reports
      highlight a rise in the incidence and prevalence of CP. However, there is limited
      data currently available concerning patients with CP undergoing exercise therapy
      (ET). We aim to prospectively examine the influence of ET on sarcopenia in
      patients with CP. Methods and analysis: A detailed evaluation of the nutritional
      condition and the daily physical activities of each participant will be conducted
      prior to entering the study. Our patients will be randomly allocated to either:
      (1) the ET group or (2) the control group. In the ET group, our patients with CP
      will receive nutritional guidance once a month. The patients with CP will also be
      instructed to perform exercises with >3 metabolic equivalents (mets; energy
      consumption in physical activities/resting metabolic rate) for 60 min/day and to
      perform exercises >23 mets/week. The primary end point will be an improvement in
      sarcopenia, defined as an increase in muscle mass and muscle strength, at 3
      months postrandomisation. A comparison of the amelioration of sarcopenia in the
      two groups will be undertaken. Ethics and dissemination: The Institutional Review
      Board at Hyogo College of Medicine approved this study protocol (approval no.
      2766). Final data will be publicly announced. A report releasing the study
      results will be submitted for publication to an appropriate journal. Trial
      registration number: UMIN000029263; Pre-results. No patient is registered at the
      submission of our manuscript.

PMID- 29333280
TI  - Correction: ProNGF-p75NTR axis plays a proinflammatory role in inflamed joints: a
      novel pathogenic mechanism in chronic arthritis.
AB  - [This corrects the article DOI: 10.1136/rmdopen-2017-000441.][This corrects the
      article DOI: 10.1136/rmdopen-2017-000441.].

PMID- 29333279
TI  - Increased supraspinatus tendon thickness following fatigue loading in rotator
      cuff tendinopathy: potential implications for exercise therapy.
AB  - Background/aim: Exercise imparts a load on tendon tissue that leads to changes in
      tendon properties. Studies suggest that loading immediately reduces tendon
      thickness, with a loss of this response in symptomatic tendinopathy. No studies
      investigating the response of tendon dimensions to load for the rotator cuff
      tendons exist. This study aimed to examine the short-term effect of loading on
      the thickness of the supraspinatus tendon and acromiohumeral distance those with
      and without rotator cuff tendinopathy. Methods: Participants were 20 painfree
      controls, and 23 people with painful rotator cuff tendinopathy. Supraspinatus
      tendon thickness and acromiohumeral distance were measured using ultrasound scans
      before, and at three time points after loading (1, 6 and 24 hours). Loading
      involved isokinetic eccentric and concentric external rotation and abduction.
      Results: There was a significant increase in supraspinatus tendon thickness in
      the pain group at 1 (7%, ?=0.38, 95% CI 0.19 to 0.57) and 6 hours (11%, ?=0.53,
      95% CI 0.34 to 0.71), although only the 6 hours difference exceeded minimal
      detectable difference. In contrast, there was a small non-significant reduction
      in thickness in controls. The acromiohumeral distance reduced significantly in
      both groups at 1 hour (controls: ?=0.64, 95% CI 0.38 to 0.90; pain: ?=1.1, 95% CI
      0.85 to 1.33), with a larger change from baseline in the pain group. Conclusion:
      Those diagnosed with painful supraspinatus tendinopathy demonstrated increased
      thickening with delayed return to baseline following loading. Rehabilitation
      professionals may need to take into account the impact of loading to fatigue when
      planning rehabilitation programmes.

PMID- 29333281
TI  - Controversies and consensus of neoadjuvant chemotherapy in soft-tissue sarcomas.
AB  - Together with surgery and radiotherapy, systemic treatment with cytotoxic
      chemotherapy and molecular targeted agents is one of the main therapeutic pillars
      in the treatment of soft-tissue sarcomas and is the mainstay of treatment in
      patients with advanced or metastatic disease. Unlike other more common
      malignancies such as breast and colorectal cancer, the role of chemotherapy when
      used in the adjuvant setting in soft-tissue sarcomas is less well defined.
      Results from prior studies have been conflicting, in part due to the
      heterogeneity and rarity of the disease, and large-scale meta-analysis has been
      performed to address this issue. Neoadjuvant chemotherapy, defined as the use of
      chemotherapy before definitive treatment with surgery or radiotherapy, has
      distinct theoretical and practical advantages, which can potentially be
      beneficial to the patient. However, the currently available evidence to support
      its use is even more scarce. In this review article, we describe the current
      established data behind the use of adjuvant chemotherapy in selected patients
      with localised soft-tissue sarcomas and, through extrapolation of available data,
      discuss the potential role of it when used in the upfront setting.

PMID- 29333283
TI  - Adverse effects of exposure to armed conflict on pregnancy: a systematic review.
AB  - Introduction: Exposure to armed conflict has manifold implications for both
      military and civilian populations. Prenatal stress has detrimental effects on
      both obstetric outcomes, fetal development and the development of an individual
      later in life. As well as causing stress to the mother, armed conflicts can
      decimate local infrastructures making it increasingly difficult to access
      antenatal and general healthcare. The present review is particularly salient in
      light of the many ongoing current conflicts. It examines the impacts of exposure
      to armed conflicts on the pregnancy outcomes. Methods: A thorough literature
      search was carried out on three databases using MeSH and truncation terms. 13
      studies were included in the final analysis relating to mothers exposed to armed
      conflicts since 1990. Results: The studies include data from 1 172 151 patients:
      mothers from Libya, Bosnia, Herzegovina, Israel, Palestine, Kosovo, Yugoslavia,
      Nepal, Somalia, Iraq, Kuwait and Afghanistan. There is evidence of an increased
      risk of mothers giving birth to babies of low birth weight as reported in nine
      included studies. All have a degree of bias, with four at lower and five at
      higher risk of bias, either not adjusting for confounders or not employing robust
      measures of exposure to conflict. Further evidence suggested an increase in the
      incidence of miscarriage, stillbirth, prematurity, congenital abnormalities,
      miscarriage and premature rupture of membranes among mothers exposed to armed
      conflict. Conclusion: Despite the varying degrees of bias which must be
      considered for the available evidence, the data with the lowest risk of bias
      suggest a relationship between exposure to armed conflict and low birth weight.
      In light of the current level of displacement experienced by such populations,
      the identification of pregnancies at risk could improve the efficacy of antenatal
      care. Clinicians should consider additional ultrasound scanning where appropriate
      to monitor for restricted growth in such pregnancies.

PMID- 29333282
TI  - Relationship between growth and illness, enteropathogens and dietary intakes in
      the first 2 years of life: findings from the MAL-ED birth cohort study.
AB  - Background: Dietary and illness factors affect risk of growth faltering; the role
      of enteropathogens is less clear. As part of the Etiology, Risk Factors and
      Interactions of Enteric Infections and Malnutrition and the Consequences for
      Child Health and Development (MAL-ED) study, we quantify the effects of
      enteropathogen infection, diarrhoea and diet on child growth. Methods: Newborns
      were enrolled and followed until 24 months. Length and weight were assessed
      monthly. Illnesses and breastfeeding practices were documented biweekly; from 9
      to 24 months, non-breast milk intakes were quantified monthly. Routinely
      collected non-diarrhoeal stools were analysed for a broad array of
      enteropathogens. A linear piecewise spline model was used to quantify
      associations of each factor with growth velocity in seven of eight MAL-ED sites;
      cumulative effects on attained size at 24 months were estimated for mean, low
      (10th percentile) and high (90th percentile) exposure levels. Additionally, the
      six most prevalent enteropathogens were evaluated for their effects on growth.
      Results: Diarrhoea did not have a statistically significant effect on growth.
      Children with high enteropathogen exposure were estimated to be 1.21+/-0.33 cm
      (p<0.001; 0.39 length for age (LAZ)) shorter and 0.08+/-0.15 kg (p=0.60; 0.08
      weight-for-age (WAZ)) lighter at 24 months, on average, than children with low
      exposure. Campylobacter and enteroaggregativeEscherichia coli detections were
      associated with deficits of 0.83+/-0.33 and 0.85+/-0.31 cm in length (p=0.011 and
      0.001) and 0.22+/-0.15 and 0.09+/-0.14 kg in weight (p=0.14 and 0.52),
      respectively. Children with low energy intakes and protein density were estimated
      to be 1.39+/-0.33 cm (p<0.001; 0.42 LAZ) shorter and 0.81+/-0.15 kg (p<0.001;
      0.65 WAZ) lighter at 24 months than those with high intakes. Conclusions:
      Reducing enteropathogen burden and improving energy and protein density of
      complementary foods could reduce stunting.

PMID- 29333285
TI  - Wealth inequality as a predictor of HIV-related knowledge in Nigeria.
AB  - Introduction: Considering the high state-level heterogeneity of HIV prevalence
      and socioeconomic characteristics in Nigeria, it is a relevant setting for
      studies into the socioeconomic correlates of HIV-related knowledge. Although the
      relationship between absolute poverty and HIV transmission has been studied, the
      role of wealth inequality in the dynamics of the HIV epidemic has yet to be
      investigated in Nigeria. The current study, therefore, investigates wealth
      inequality and other sociodemographic covariates as predictors of HIV-related
      knowledge, in order to identify subgroups of the Nigerian population that would
      benefit from HIV preventive interventions. Methods: This study used the
      nationally representative 2013 Nigerian Demographic and Health Survey (NDHS). HIV
      related knowledge was computed as a total score based on HIV-related knowledge
      indicators in the NDHS, dichotomised using the sample median as the cut-off.
      Wealth inequality and other relevant sociodemographic variables were introduced
      into a logistic regression model based on their significance in bivariate
      analyses. ORs derived from the model were interpreted to identify risk groups for
      low HIV-related knowledge after adjusting for confounding factors. Results: The
      regression model indicated that individuals with lower literacy levels were
      almost twice as likely as literate respondents to have low HIV-related knowledge
      (adjusted OR (AOR): 1.95, 95% CI 1.85 to 2.05, P<0.001), and individuals in the
      upper wealth quintile were less than half as likely than those in the lower
      wealth quintile to have low HIV-related knowledge (AOR: 0.40, 95% CI 0.35 to
      0.46, P<0.001). Women were also more than twice as likely as men to have low HIV
      related knowledge at each level of wealth inequality. In addition, women were 80%
      less likely to have low mother-to-child transmission knowledge than men, but had
      over 1.5 times higher odds of having poor knowledge of HIV risk reduction
      measures. Ethnicity, religious affiliation, relationship status and residing in
      rural areas were additional significant predictors of HIV-related knowledge.
      Conclusion: HIV-related knowledge in this sample is generally low among women,
      those with low literacy levels, the poor, the unemployed, those residing in rural
      areas, those with traditional religious beliefs and those living in states with
      the highest wealth inequality ratios. The identification of these risk groups for
      low HIV-related knowledge facilitates the implementation of future evidence-based
      interventions among these groups in order to potentially reduce HIV transmission.

PMID- 29333284
TI  - Does greater individual social capital improve the management of hypertension?
      Cross-national analysis of 61 229 individuals in 21 countries.
AB  - Introduction: Social capital, characterised by trust, reciprocity and
      cooperation, is positively associated with a number of health outcomes. We test
      the hypothesis that among hypertensive individuals, those with greater social
      capital are more likely to have their hypertension detected, treated and
      controlled. Methods: Cross-sectional data from 21 countries in the Prospective
      Urban and Rural Epidemiology study were collected covering 61 229 hypertensive
      individuals aged 35-70 years, their households and the 656 communities in which
      they live. Outcomes include whether hypertensive participants have their
      condition detected, treated and/or controlled. Multivariate statistical models
      adjusting for community fixed effects were used to assess the associations of
      three social capital measures: (1) membership of any social organisation, (2)
      trust in other people and (3) trust in organisations, stratified into high-income
      and low-income country samples. Results: In low-income countries, membership of
      any social organisation was associated with a 3% greater likelihood of having
      one's hypertension detected and controlled, while greater trust in organisations
      significantly increased the likelihood of detection by 4%. These associations
      were not observed among participants in high-income countries. Conclusion:
      Although the observed associations are modest, some aspects of social capital are
      associated with better management of hypertension in low-income countries where
      health systems are often weak. Given that hypertension affects millions in these
      countries, even modest gains at all points along the treatment pathway could
      improve management for many, and translate into the prevention of thousands of
      cardiovascular events each year.

PMID- 29333286
TI  - Prevalence and determinants of tobacco use among young people in The Gambia.
AB  - Introduction: Tobacco consumption and consequent morbidity and mortality are
      expected to grow most markedly over coming decades in low-income and middle
      income countries (LMICs). Preventing tobacco experimentation and uptake among
      young people in LMICs is therefore vital. However, data on smoking in these
      countries, particularly in sub-Saharan Africa, remain sparse. Method: We used two
      stage cluster random sampling to select students in upper and senior secondary
      schools throughout The Gambia, and a self-administered questionnaire to collect
      data on their tobacco use, risk factors and demographic details. Results: Of 10
      392 eligible students, 10 289 (99%; 55% girls and 44% boys, age 12-20 years)
      participated. The prevalence of ever smoking cigarettes, cigars or pipes was
      16.7% (25.7% boys and 9.4% girls) and current (past 30 days) smoking 4.5% (7.9%
      boys and 1.5% girls). Smoking was more common among students attending private
      schools (OR 1.69, 95% CI 1.29 to 2.22), of Christian or other faiths compared
      with Muslims, living with parents (OR 1.39, 95% CI 1.06 to 1.81), who had smoking
      allowed in their homes (OR 1.67, 95% CI 1.30 to 2.13), with family members who
      smoked or had one or more friends who smoked. Most (55.6%) smokers want to stop,
      but only 22% received any stop smoking support. Ever smoking of shisha, at 8.1%,
      was unexpectedly high, and relatively prevalent among girls (11.4% of boys and
      5.4% of girls). Conclusions: Tobacco use is common among young people in The
      Gambia. Shisha smoking is also common in this population, and in relative terms
      especially among girls. Further work is required to determine whether this is a
      problem local to The Gambia or reflects a wider pattern of tobacco use in sub
      Saharan Africa.

PMID- 29333287
TI  - Vertical and horizontal equity of funding for malaria control: a global
      multisource funding analysis for 2006-2010.
AB  - Background: International and domestic funding for malaria is critically
      important to achieve the Sustainable Development Goals. Its equitable
      distribution is key in ensuring that the available, scarce, resources are
      deployed efficiently for improved progress and a sustained response that enables
      eradication. Methods: We used concentration curves and concentration indices to
      assess inequalities in malaria funding by different donors across countries,
      measuring both horizontal and vertical equity. Horizontal equity assesses whether
      funding is distributed in proportion to health needs, whereas vertical equity
      examines whether unequal economic needs are addressed by appropriately unequal
      funding. We computed the Health Inequity Index and the Kakwani Index to assess
      the former and the latter, respectively. We used data from the World Bank, Global
      Fund, Unicef, President's Malaria Initiative and the Malaria Atlas Project to
      assess the distribution of funding against need for 94 countries. National gross
      domestic product per capita was used as a proxy for economic need and 'population
      at-risk' for health need. Findings: The level and direction of inequity varies
      across funding sources. Unicef and the President's Malaria Initiative were the
      most horizontally inequitable (pro-poor). Inequity as shown by the Health
      Inequity Index for Unicef decreased from -0.40 (P<0.05) in 2006 to -0.25 (P<0.10)
      in 2008, and increased again to -0.58 (P<0.01) in 2009. For President's Malaria
      Initiative, it increased from -0.19 (P>0.10) in 2006 to -0.38 (P<0.05) in 2008,
      and decreased to -0.36 (P<0.10) in 2010. Domestic funding was inequitable (pro
      rich) with inequity increasing from 0.28 (P<0.01) in 2006 to 0.39 (P<0.01) in
      2009, and then decreasing to 0.22 (P<0.10) in 2010. Funding from the World Bank
      and the Global Fund was distributed proportionally according to need. In terms of
      vertical inequity, all sources were progressive: Unicef and the President's
      Malaria Initiative were the most progressive with the Kakwani Indices ranging
      from -0.97 (P<0.01) to -1.29 (P<0.01), and -0.90 (P<0.01) to -1.10 (P<0.01),
      respectively. Conclusion: Our results suggest that external funding of malaria
      treatment tends to be allocated to countries with higher health and economic need
      but not in proportion to their relative health need and income when compared to
      other countries. While malaria eradication might require funders to
      disproportionally allocate funding that goes beyond (financial and health) need,
      our analysis highlights that funders might potentially be targeting in excess
      certain countries. Regular assessments of need and greater coordination among
      donors are necessary for equitable resource allocation, to improve and sustain
      progress with malaria control and elimination.

PMID- 29333289
TI  - Localized Single-Cell Lysis and Manipulation Using Optothermally-Induced Bubbles.
AB  - Localized single cells can be lysed precisely and selectively using microbubbles
      optothermally generated by microsecond laser pulses. The shear stress from the
      microstreaming surrounding laser-induced microbubbles and direct contact with the
      surface of expanding bubbles cause the rupture of targeted cell membranes. High
      resolution single-cell lysis is demonstrated: cells adjacent to targeted cells
      are not lysed. It is also shown that only a portion of the cell membrane can be
      punctured using this method. Both suspension and adherent cell types can be lysed
      in this system, and cell manipulation can be integrated for cell-cell interaction
      studies.

PMID- 29333288
TI  - Variations in disability and quality of life with age and sex between eight lower
      income and middle-income countries: data from the INDEPTH WHO-SAGE collaboration.
AB  - Background: Disability and quality of life are key outcomes for older people.
      Little is known about how these measures vary with age and gender across lower
      income and middle-income countries; such information is necessary to tailor
      health and social care policy to promote healthy ageing and minimise disability.
      Methods: We analysed data from participants aged 50 years and over from health
      and demographic surveillance system sites of the International Network for the
      Demographic Evaluation of Populations and their Health Network in Ghana, Kenya,
      Tanzania, South Africa, Vietnam, India, Indonesia and Bangladesh, using an
      abbreviated version of the WHO Study on global AGEing survey instrument. We used
      the eight-item WHO Quality of Life (WHOQoL) tool to measure quality of life and
      theWHO Disability Assessment Schedule, version 2 (WHODAS-II) tool to measure
      disability. We collected selected health status measures via the survey
      instrument and collected demographic and socioeconomic data from linked
      surveillance site information. We performed regression analyses to quantify
      differences between countries in the relationship between age, gender and both
      quality of life and disability, and we used anchoring vignettes to account for
      differences in interpretation of disability severity. Results: We included 43 935
      individuals in the analysis. Mean age was 63.7 years (SD 9.7) and 24 434 (55.6%)
      were women. In unadjusted analyses across all countries, WHOQoL scores worsened
      by 0.13 points (95% CI 0.12 to 0.14) per year increase in age and WHODAS scores
      worsened by 0.60 points (95% CI 0.57 to 0.64). WHODAS-II and WHOQoL scores varied
      markedly between countries, as did the gradient of scores with increasing age. In
      regression analyses, differences were not fully explained by age, socioeconomic
      status, marital status, education or health factors. Differences in disability
      scores between countries were not explained by differences in anchoring vignette
      responses. Conclusions: The relationship between age, sex and both disability and
      quality of life varies between countries. The findings may guide tailoring of
      interventions to individual country needs, although these associations require
      further study.

PMID- 29333290
TI  - Clinical Characteristics and Surgical Procedures for Children with Congenital
      Membranous Cataract.
AB  - Objective: In a group case series, the clinical characteristics of congenital
      membranous cataract in children were studied to establish a system of
      classification and determine the surgical method suited for each type. Methods:
      Children (18 eyes) with congenital membranous cataract were examined by slit
      lamp, ultrasound biomicroscopy, and operating microscopy to classify cataracts.
      The clinical characteristics of congenital membranous cataract and its feature
      related to the surgical method were analyzed. Results: Five major types of
      congenital membranous cataracts were classified. All of the surgeries were
      successful. Anterior and posterior capsulorhexis was performed using Kloti RF
      capsulotomy tips. The capsular flap was removed, and anterior vitrectomy was
      performed using a vitrectomy cutter. Postoperative complications included
      posterior capsule opacification in 16.7% of the patients. Conclusion: Ultrasound
      biomicroscopy was used successfully to classify congenital membranous cataracts
      prior to surgery. Anterior and posterior capsulorhexis was performed using Kloti
      RF capsulotomy tips, and capsulectomy was performed using a vitrectomy cutter.
      These were effective techniques and should be considered for congenital
      membranous cataract removal surgery. This trial is registered with registration
      number chiCTR-OOC-17010913.

PMID- 29333291
TI  - The Effect of Perioperative Topical Ketorolac 0.5% on Macular Thickness after
      Uneventful Phacoemulsification.
AB  - Background: To evaluate the effects of topical 0.5% ketorolac treatment combined
      with topical steroids on macular thickness in cases who had uneventful
      phacoemulsification surgery. Methods: 58 eyes of 58 consecutive cases were
      included. The mean foveal thickness (MFT), parafoveal thickness (ParaFT), and
      perifoveal thickness (PeriFT) measurements were performed with optical coherence
      tomography (RTVue-100, Optovue, Fremont, CA, USA) preoperatively and at
      postoperative 1 week, 1 month, and 2 months. All cases received topical 0.1%
      dexamethasone postoperatively. Randomly selected cases additionally received
      topical 0.5% ketorolac, which started 2 days prior to surgery. Cases who received
      both topical steroids and ketorolac formed group 1 and subjects who received only
      topical steroids formed group 2. Results: The increase in mean MFT at the 1st
      week, 1st month, and 2nd months after surgery in group 1 was significantly lower
      than group 2 (P = 0.008, P <= 0.001, and P <= 0.001, resp.). In group 1, the
      increase in mean ParaFT and PeriFT was significantly lower than group 2 at the
      1st and 2nd months of the surgery (P < 0.05 for all variables). Conclusions:
      Topical ketorolac combined with steroids is highly efficacious in order to
      prevent increment in thickness on each part of the macula even after an
      uneventful phacoemulsification surgery comparing to steroid monotheraphy.

PMID- 29333292
TI  - Applying Sutureless Encircling Number 41 Band and Transscleral Chandelier
      Assisted Laser Retinopexy for Scleral Buckling Procedure.
AB  - Purpose: To assess the outcome of sutureless encirlcing number 41 band and
      transscleral laser retinopexy in uncomplicated rhegmatogenous retinal detachment
      (RRD), using a wide-angle viewing system (WAVS) and chandelier endoillumination.
      Methods: Prospective intervention study included 30 eyes of 30 patients
      presenting with RRD of recent onset indicated for SB. All cases were treated by
      sutureless encircling number 41 band and transscleral laser retinopexy.
      Visualization was provided by the Resight WAVS and a single 27-gauge chandelier
      endoillumination. Anatomical and visual outcomes were evaluated. Results: The
      mean age of our group was 49.8 +/- 12.3 years, and the mean duration of RD was 7
      (0-50) days. Twenty-four eyes (80.0%) were phakic while the remaining 6 eyes
      (20%) were either pseudophakic or aphakic. The primary retinal reattachment rate
      was 83.3% (25 out of 30 eyes). LogMAR visual acuity improved from 1.3 (0.30-2.0)
      preoperatively to 1.0 (0.40-1.60) at first month (p = 0.002) and to 0.70 (0.20
      1.92) at third month (p < 0.001). Conclusion: Sutureless encircling number 41
      band with chandelier-assisted transscleral laser retinopexy is a safe and
      effective technique for managing uncomplicated RRD. It provides a high primary
      success rate while eliminating the complications of cryotherapy, sutures, and
      broad buckles.

PMID- 29333293
TI  - Corrigendum to "Genotype-Phenotype Characterization of Novel Variants in Six
      Italian Patients with Familial Exudative Vitreoretinopathy".
AB  - [This corrects the article DOI: 10.1155/2017/3080245.].

PMID- 29333294
TI  - Addressing Adolescent Depression in Tanzania: Positive Primary Care Workforce
      Outcomes Using a Training Cascade Model.
AB  - Background: This is a report on the outcomes of a training program for community
      clinic healthcare providers in identification, diagnosis, and treatment of
      adolescent Depression in Tanzania using a training cascade model. Methods: Lead
      trainers adapted a Canadian certified adolescent Depression program for use in
      Tanzania to train clinic healthcare providers in the identification, diagnosis,
      and treatment of Depression in young people. As part of this training program,
      the knowledge, attitudes, and a number of other outcomes pertaining to healthcare
      providers and healthcare practice were assessed. Results: The program
      significantly, substantially, and sustainably improved provider knowledge and
      confidence. Further, healthcare providers' personal help-seeking efficacy also
      significantly increased as well as the clinicians' reported number of adolescent
      patients identified, diagnosed, and treated for Depression. Conclusion: To our
      knowledge, this is the first study reporting positive outcomes of a training
      program addressing adolescent Depression in Tanzanian community clinics. These
      results suggest that the application of this training cascade approach may be a
      feasible model for developing the capacity of healthcare providers to address
      youth Depression in a low-income, low-resource setting.

PMID- 29333295
TI  - Serial Galactose-Deficient IgA1 Levels in Children with IgA Nephropathy and
      Healthy Controls.
AB  - Galactose-deficient IgA1 (Gd-IgA1) is a key pathogenic factor for IgA nephropathy
      (IgAN) and a potential biomarker for the disease. This study examined serial
      serum Gd-IgA1 levels over 1 year in 13 children with IgAN and 40 healthy
      children, to determine whether or not serum Gd-IgA1 levels changed over time.
      Subjects were younger than 18 years of age. Follow-up measurements were scheduled
      6 and/or 12 months later. Analysis of variance and regression models for repeated
      measures were used to estimate group and time effects. Serum Gd-IgA1 level was
      higher in initial samples for IgAN patients compared to those of healthy children
      (P < 0.0001). Serum Gd-IgA1 levels did not change over time for healthy controls
      but increased for IgAN patients (P = 0.001). Serum Gd-IgA1 level was elevated for
      9 children with IgAN at study entry and remained elevated. Two of the 4 IgAN
      patients with initially normal Gd-IgA1 levels had a subsequent elevated level.
      The persistent elevation of the serum Gd-IgA1 level in children with IgAN
      enhances its utility as a potential diagnostic test for IgAN.

PMID- 29333296
TI  - Determinants of Malaria Prevention and Treatment Seeking Behaviours of Pregnant
      Undergraduates Resident in University Hostels, South-East Nigeria.
AB  - This cross-sectional descriptive survey investigated determinants of malaria
      prevention and treatment seeking behaviours of pregnant undergraduates resident
      in university hostels, South-East Nigeria. Purposive sampling was used to enrol
      121 accessible and consenting undergraduates with self-revealed and noticeable
      pregnancy residing in twenty-three female hostels of four university campuses in
      Enugu State, Nigeria. Structured interview guide developed based on reviewed
      literature and WHO-recommended malaria prevention and treatment measures was used
      to collect students' self-report data on malaria preventive health behaviours,
      sick role behaviours, and clinic use using mixed methods. The WHO-recommended
      malaria prevention measures were sparingly used. Some believed that pregnancy
      does not play any role in a woman's reaction to malaria infection. Only 41
      (50.6%) visited a hospital for screening and treatment. Thirty-four (28.1%) used
      antimalaria medicine bought from chemist shop or over-the-counter medicines,
      while 33 (27.3%) used untreated net. The students were more likely to complete
      their antimalaria medicine when they were sick with malaria infection than for
      prevention (p = 0.0186). Knowledge, academic schedule, cultural influence on
      perception and decision-making, and accessibility of health facility were key
      determinants of the women's preventive and treatment seeking behaviours. Health
      education on malaria prevention and dangers of drug abuse should form part of
      orientation lectures for all freshmen. University health centres should be
      upgraded to provide basic antenatal care services.

PMID- 29333297
TI  - Metronomic Chemotherapy in Triple-Negative Metastatic Breast Cancer: The Future
      Is Now?
AB  - Triple-negative breast cancer (TNBC) shows a very bad prognosis, even in early
      stages of disease. Metronomic chemotherapy refers to the minimum biologically
      effective dose of a chemotherapy agent given as a continuous dosing regimen with
      no prolonged drug-free breaks that leads to antitumor activity. In the present
      article, we review preclinical and clinical data of metronomic administration of
      chemotherapy agents with or without biological agents in TNBC cell lines and
      patients, contextually reporting data from the VICTOR-2 study in the subgroup of
      patients with TNBC, in order to stimulate new ideas for the design of clinical
      trials in this subset of patients.

PMID- 29333298
TI  - Inability to Utilize Retrograde Cardioplegia due to a Persistent Left Superior
      Vena Cava.
AB  - A persistent left superior vena cava is a congenital abnormality that affects a
      minority of the general population. While this finding is not hemodynamically
      significant in all patients, failure to recognize the altered anatomy in any of
      these patients can be consequential during procedures such as central venous
      catheter placement, pacemaker/defibrillator wire placement, and use of retrograde
      cardioplegia during cardiac surgery. We present a case of an intraoperative
      diagnosis of a persistent left superior vena cava that altered the original plan
      to arrest the heart using retrograde cardioplegia. Echocardiography was
      instrumental in this diagnosis and avoided potentially inadequate myocardial
      protection during cardiopulmonary bypass.

PMID- 29333299
TI  - Ventricular Fibrillation following Varicella Zoster Myocarditis.
AB  - Varicella-zoster virus (VZV) infection can rarely lead to serious cardiac
      complications and life-threatening arrhythmias. We present a case of a 46-year
      old male patient who developed VZV myocarditis and presented with recurrent
      syncopal episodes followed by a cardiac arrest. He had a further collapse eight
      years later, and cardiac magnetic resonance imaging (MRI) demonstrated mild mid
      wall basal and inferolateral wall fibrosis. He was treated with an implantable
      cardioverter defibrillator (ICD) and represented two years later with ICD shocks,
      and interrogation of the device revealed ventricular fibrillation episodes. This
      case demonstrates the life-threatening long-term sequelae of VZV myocarditis in
      adults. We suggest that VZV myocarditis should be considered in all patients who
      present with a syncopal event after VZV infection. In these patients, ICD
      implantation is a potentially life-saving procedure.

PMID- 29333300
TI  - Cyclic Nonrespiratory Pulse Pressure Oscillations Caused by Atrioventricular
      Dissociation.
AB  - Dynamic preload assessment tests, especially pulse pressure variation (PPV) and
      stroke volume variation (SVV), are increasingly acknowledged in mechanically
      ventilated patients as being predictors of fluid responsiveness. However, the
      limitations of this method are often neglected or overlooked. One of the
      prerequisites for PPV and SVV evaluation, in addition to intermittent positive
      pressure ventilation, is a "regular heart rhythm," which may be an ambiguous
      term. We present a case where, despite a regular (paced) rhythm, atrioventricular
      dissociation was present and resulted in marked PPV elevation, which subsequently
      disappeared once sinus rhythm returned. Our case indicates that PPV and SVV
      should be interpreted with caution when atrioventricular dissociation is present.

PMID- 29333301
TI  - A Case of Segmental Arterial Mediolysis Presenting as Mucosal Gastric Hematoma.
AB  - Background: Although segmental arterial mediolysis (SAM) has been increasingly
      recognized as arteriopathy and there are some case reports about SAM, it is still
      very rare. It is characterized clinically by aneurysm, dissection, stenosis, and
      occlusion within splanchnic arterial branches, causing intra-abdominal hemorrhage
      or bowel ischemia. Mortality is as high as 50% in acute events. Case
      Presentation: A 51-year-old man was referred to our hospital with hematemesis.
      Gastroscopy revealed a submucosal-like tumor on the posterior wall of gastric
      angle with ulceration. Computed tomography indicated a tumor measuring 65 * 50 mm
      in the stomach, which was suspected to have invaded into the pancreas.
      Significant hematemesis recurred; the patient developed shock and underwent
      emergency distal gastrectomy, distal pancreatectomy, and splenectomy. The
      pathology and the clinical course were compatible with SAM splenic artery rupture
      causing retroperitoneal hemorrhage that penetrated into the stomach. After that
      surgery, aneurysm of common hepatic artery ruptured and coil embolization was
      performed. Conclusion: SAM is an important cause of intra-abdominal or
      retroperitoneal hemorrhage in patients without underlying disease. SAM typically
      presents as intra-abdominal hemorrhage, but, in this case, the retroperitoneal
      hemorrhage penetrated into the stomach and it looked like a submucosal tumor.

PMID- 29333302
TI  - A Mysterious DRESS Case: Autoimmune Enteropathy Associated with DRESS Syndrome.
AB  - Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) is a rare but
      potentially life-threatening cutaneous hypersensitivity reaction characterized by
      extensive mucocutaneous eruption, fever, hematologic abnormalities, and extensive
      organ involvement. Here, we present a case of a young woman with DRESS syndrome
      following exposure to vancomycin with renal, cutaneous, and gastrointestinal
      involvement. To the best of our knowledge, this is the first case description in
      the literature of DRESS of the gastrointestinal tract with autoimmune
      enteropathy.

PMID- 29333303
TI  - Schinzel-Giedion Syndrome with Congenital Megacalycosis in a Turkish Patient:
      Report of SETBP1 Mutation and Literature Review of the Clinical Features.
AB  - Schinzel-Giedion syndrome (SGS) is a rare autosomal dominant disorder that
      results in facial dysmorphism, multiple congenital anomalies, and an increased
      risk of malignancy. Recently, using exome sequencing, de novo heterozygous
      mutations in the SETBP1 gene have been identified in patients with SGS. Most
      affected individuals do not survive after childhood because of the severity of
      this disorder. Here, we report SETBP1 mutation confirmed by molecular analysis in
      a case of SGS with congenital megacalycosis.

PMID- 29333304
TI  - Synthetic Cannabinoid Abuse and a Rare Alpha-1-Antitrypsin Mutant Causing Acute
      Fulminant Hepatitis: A Case Report and Review of the Literature.
AB  - Synthetic cannabinoids (SCs) abuse is on the rise because they are easily
      obtained over the counter; they are potent psychoactive compounds and routine
      drug testing does not detect them. As their abuse is on the rise, so are their
      detrimental side effects; however, the occurrence of acute hepatitis due to SCs
      abuse has been reported only once before. In this case, testing revealed that the
      patient was also heterozygous for alpha-1-antitrypsin (A-1-AT) with the phenotype
      of PI*EM. This mutant phenotype has never been reported as a cause of A-1-AT
      disease and the abuse of SCs in a patient with this phenotype has also never been
      reported. This case illustrates the possible need to expand routine drug testing
      for SCs and consider A-1-AT phenotyping in certain clinical scenarios.

PMID- 29333305
TI  - A Rare Case of Transient Proximal Renal Tubular Acidosis in Pregnancy.
AB  - Renal tubular acidosis (RTA) is a disorder that has improper function of renal
      acid-base regulation and is rarely encountered during pregnancy. Currently, there
      is no clear evidence on management and outcomes in patients with this condition.
      We report a case of a previously healthy 23-year-old female at 30 weeks of
      gestation who presented with proximal RTA and had spontaneous resolution of the
      condition shortly after delivery.

PMID- 29333306
TI  - Acute Cervical Dystonia Induced by Clebopride.
AB  - Antidopaminergic drugs are known to induce extrapyramidal symptoms. Clebopride, a
      dopamine antagonist, also can produce parkinsonism, tardive dyskinesia, tardive
      dystonia, hemifacial dystonia, or oculogyric crisis; however, acute dystonic
      reaction caused by clebopride has not been reported in adults. We report two
      young men who experienced acute cervical dystonia within a few days of taking
      clebopride. The patients recovered after discontinuation of the drug. Physicians
      prescribing clebopride should be aware of the adverse effects of this drug.

PMID- 29333307
TI  - Recurrent Cesarean Scar Ectopic Pregnancy Treated with Systemic Methotrexate.
AB  - Cesarean scar pregnancy (CSP) is a rare event; however its incidence has been
      rising due to the increasing rates of cesarean deliveries. The majority of cases
      present with signs or symptoms requiring surgery, which often results in
      hysterectomy. The recurrence of CSP is even rarer with only few cases which have
      been reported. This is a report of recurrent cesarean scar ectopic pregnancy
      (RCSP) that was promptly diagnosed and managed with only systemic methotrexate.
      This was a 30-year-old woman, with a history of two prior cesarean deliveries
      followed by a CSP, who presented at 5 weeks and 3 days of gestation for her first
      prenatal visit. Transvaginal ultrasound revealed a RCSP. Her serum beta-human
      chorionic gonadotropin (beta-hCG) level was 54,295 IU/L. The first CSP, which was
      diagnosed at a later stage, was treated with uterine artery embolization and
      systemic methotrexate leading to complete resolution within 10 weeks. The current
      ectopic was treated with two doses of systemic methotrexate; her serum beta-hCG
      reached undetectable levels within 7 weeks. Thus, patients with a history of
      prior CSP should be carefully monitored with transvaginal ultrasound during
      subsequent pregnancies to allow early diagnosis of RCSP, which could then be
      treated conservatively.

PMID- 29333308
TI  - Recurrent Gastrointestinal Stromal Tumors in the Imatinib Mesylate Era: Treatment
      Strategies for an Incurable Disease.
AB  - Introduction: Recurrence of gastrointestinal stromal tumors (GISTs) after
      surgical resection and imatinib mesylate (IM) adjuvant therapy poses a
      significant treatment challenge. We present the case of a patient who underwent
      surgical resection after recurrence and review the current literature regarding
      treatment. Case Presentation: A 58-year-old man with a large intra-abdominal
      jejunal GIST was treated with complete surgical resection followed by IM. The
      patient experienced disease recurrence 3.5 years later and underwent IM dose
      escalation and reresection. Conclusion: Current strategies to treat recurrent
      GIST include dose escalation, modifying adjuvant tyrosine kinase inhibitor
      therapy, and surgery. High-level evidence will be required to better define the
      combinatory roles of tyrosine kinase inhibitor therapy, guided by molecular
      profiling, and surgery in the management of recurrent GIST.

PMID- 29333309
TI  - Intraperitoneal Granulomas Unexpectedly Found during a Cesarean Delivery: A Late
      Complication of Dropped Gallstones.
AB  - Laparoscopic cholecystectomy is the treatment of choice for patients with
      symptomatic cholelithiasis. Spillage of gallstones into the abdominal cavity
      during laparoscopic cholecystectomy occurs in approximately one-third of cases.
      Although retained gallstones remain asymptomatic, few cases may develop
      complications. We report the case of a 29-year-old nulliparous woman presenting
      with several hard nodules in the omentum, raising the possibility of a metastatic
      disease. Histological examination demonstrated a bile-stained material and a
      foreign body-type granulomatous response without neoplastic tissue. Our case
      demonstrates an example of a complication resulting two years after a
      laparoscopic cholecystectomy that was unexpectedly found during a cesarean
      delivery. Pathologists should be aware of this entity to avoid interpretation
      errors.

PMID- 29333310
TI  - Hemiataxia: A Novel Presentation of Anti-NMDA Receptor Antibody Mediated
      Encephalitis in an Adolescent.
AB  - Anti-NMDA receptor antibody associated encephalitis as a cause of new-onset
      neuropsychiatric manifestations in children and adults can represent a
      significant diagnostic challenge for clinicians. Clinical signs often include
      encephalopathy, new-onset psychosis, and movement phenomenon. Although orofacial
      dyskinesias were initially identified as a characteristic movement phenomenon in
      this type of encephalitis, an expanded range of abnormalities has recently been
      reported, including isolated ataxia. We report a case of isolated hemiataxia in a
      young adult with mild initial psychiatric manifestations. A personal and family
      history of preceding neuropsychiatric symptoms produced diagnostic confusion and
      resulted in a significant diagnostic and therapeutic delay. Our case confirms the
      unilateral movement manifestations that have been emphasized in recent reports.
      Additionally, it confirms the need for involvement of neurologic as well as
      psychiatric services in the evaluation of such cases and emphasizes the
      importance of the neurologic examination in presentations with an initial
      psychiatric predominance.

PMID- 29333312
TI  - Mesh Migration into the J-Pouch in a Patient with Post-Ulcerative Colitis
      Colectomy: A Case Report and Literature Review.
AB  - Mesh repair offers advantages like lower postsurgical pain and earlier return to
      work. Thus, it has become a widely used treatment option. Here, we present the
      first case report of a mesh migration into a J-pouch in a patient with history of
      ulcerative colitis who underwent total abdominal colectomy with J-pouch and
      ileoanal anastomosis and a subsequent laparoscopic ventral hernia repair with
      mesh.

PMID- 29333311
TI  - An Uncommon Case of Bilateral Breast Enlargement Diagnosed as Tumoral
      Pseudoangiomatous Stromal Hyperplasia: Imaging and Pathological Findings.
AB  - The incidence of reported pseudoangiomatous stromal hyperplasia (PASH), as well
      as the variability and severity of clinical presentations, is increasing in the
      literature. In parallel, several authors posit the need for an improved
      classification of PASH to avoid possible variables associated with this
      diagnosis. Here, we present a 25-year-old woman with PASH accompanied by severe
      bilateral and symmetrical breasts enlargement, highlighting an uncommon clinical
      presentation of PASH as much as the careful interdisciplinary review and
      correlation of histology and all available imaging studies to confirm the
      definitive diagnosis.

PMID- 29333313
TI  - Retroperitoneal Necrotizing Fasciitis from Fournier's Gangrene in an
      Immunocompromised Patient.
AB  - Introduction: Necrotizing fasciitis (NF) is a devastating soft tissue disease
      causing fulminant clinical deterioration, and extension into the retroperitoneum
      has a high mortality rate. This disease process demands a strong clinical
      suspicion for early identification which must be coupled with frequent wide
      surgical debridements and intravenous antibiotics for improved outcomes. Various
      clinical risk factors may render a weakness in the patient's immune status
      including diabetes mellitus, chronic renal failure, obesity, and autoimmune
      disorders, such as a human immunodeficiency virus (HIV) infection. Case Report: A
      55-year-old male presented with hypotension requiring a large intravenous fluid
      resuscitation and vasopressors. He was diagnosed with the human immunodeficiency
      virus upon presentation. A computerized tomographic scan revealed air and fluid
      in the perineum and pelvis, ascending into the retroperitoneum. Multiple surgical
      debridements to his perineum, deep pelvic structures, and retroperitoneum were
      completed. After colostomy placement, antibiotic administration, and wound care,
      he was closed using split-thickness skin grafting. Conclusion: NF is a sinister
      and fulminant disease requiring prompt diagnosis and surgical intervention. The
      best chance for survival occurs with emergent surgical debridement and
      appropriate intravenous antibiotics. While retroperitoneal NF is consistent with
      uniformly poor outcomes, patients are best treated in an American Burn
      Association-verified burn center.

PMID- 29333314
TI  - A Case of Small Bowel Obstruction and Enterocutaneous Fistulation Resulting from
      a Mesenteric Haematoma following Blunt Abdominal Trauma.
AB  - A 23-year-old male with a history of previous abdominal surgery was involved in a
      road traffic accident. He was discharged after initial assessment but represented
      several days with small bowel obstruction secondary to a mesenteric haematoma. He
      underwent resection and recovered well but represented later on the day of
      discharge with a leaking surgical wound consistent with an enterocutaneous
      fistula. This was managed conservatively and closed spontaneously after ten days.
      This case serves to highlight that adhesions from previous surgery can tether the
      small bowel causing mesenteric injury following blunt-force trauma. It also
      demonstrates that postoperative ileus can result in an enterocutaneous fistula
      that has the appearance of an anastomotic breakdown but which resolves more
      rapidly.

PMID- 29333315
TI  - Early Contextual Fear Memory Deficits in a Double-Transgenic Amyloid-beta
      Precursor Protein/Presenilin 2 Mouse Model of Alzheimer's Disease.
AB  - Presenilin 1 and presenilin 2 (PS1 and PS2) play a critical role in gamma
      secretase-mediated cleavage of amyloid-beta precursor protein (APP) and the
      subsequent generation of beta-amyloid peptides. The purpose of the present study
      was to test whether PS2 mutation accelerates the onset of contextual fear memory
      deficits in a mouse model of AD that expresses a mutation (K670N/M671L) of the
      human APP with the Swedish mutation (Tg2576 mice). In the present study, an
      APP/PS2 double-transgenic mouse model (PS2Tg2576) was generated by crossbreeding
      transgenic mice carrying the human mutant PS2 (N141I) with Tg2576 mice.
      Contextual fear conditioning was tested in PS2Tg2576 mice aged 3, 4, 6, and 10-12
      months. PS2Tg2576 mice showed a tendency of lower freezing behavior as early as 3
      months of age, but significant memory impairment was observed from the age of 4
      months. The cognitive impairment was more prominent at ages of 6 and 10-12
      months. In contrast, Tg2576 mice aged 3 and 4 months exhibited successful
      acquisition of contextual fear learning, but Tg2576 mice aged 6 months or older
      showed significantly impaired fear memory. These results show that PS2 mutation
      significantly accelerates the onset of fear memory deficits in the APP AD model
      mice.

PMID- 29333316
TI  - Impact of Mezieres Rehabilitative Method in Patients with Parkinson's Disease: A
      Randomized Controlled Trial.
AB  - The aim of this study was to assess the efficacy of Mezieres method in improving
      trunk flexibility of the back muscles and balance in patients with Parkinson's
      disease (PD). Materials and Methods. Thirty-six patients were randomized into 2
      groups: the Mezieres treatment group and the control group (home exercise group).
      The primary outcome was the improvement in balance per the Berg Balance Scale
      (BBS) and the trunk flexibility of the back for the anterior flexion trunk test.
      Also, we evaluated pain, gait balance for the Functional Gait Assessment (FGA),
      disease-related disability for the Modified Parkinson's Activity Scale and the
      Unified Parkinson's Disease Rating Scale (UPDRS), the quality of life, and the
      functional exercise capacity. All the measures were evaluated at baseline (T0),
      at the end of the rehabilitative program (T1), and at the 12-week follow-up (T2).
      Results. In the Mezieres group, the BBS (p < .001) and trunk flexion test (p <
      .001) improved significantly at T1 and remained the same at T2. Between groups,
      significant changes were reported in FGA (p = .027) and UPDRS Total (p = .007) at
      T1 and in FGA (p = .03) at T2. Conclusion. The Mezieres approach is efficacious
      in improving the flexibility of the trunk and balance in PD patients.

PMID- 29333318
TI  - Evaluation of Global Genomic DNA Methylation in Human Whole Blood by Capillary
      Electrophoresis UV Detection.
AB  - Alterations in global DNA methylation are implicated in various
      pathophysiological processes. The development of simple and quick, yet robust,
      methods to assess DNA methylation is required to facilitate its measurement and
      interpretation in clinical practice. We describe a highly sensitive and
      reproducible capillary electrophoresis method with UV detection for the
      separation and detection of cytosine and methylcytosine, after formic acid
      hydrolysis of DNA extracted from human whole blood. Hydrolysed samples were dried
      and resuspended with water and directly injected into the capillary without
      sample derivatization procedures. The use of a run buffer containing 50 mmol/L
      BIS-TRIS propane (BTP) phosphate buffer at pH 3.25 and 60 mmol/L sodium acetate
      buffer at pH 3.60 (4 : 1, v/v) allowed full analyte identification within 11 min.
      Precision tests indicated an elevated reproducibility with an interassay CV of
      1.98% when starting from 2 MUg of the extracted DNA. The method was successfully
      tested by measuring the DNA methylation degree both in healthy volunteers and in
      reference calf thymus DNA.

PMID- 29333319
TI  - Comparative Liquid Chromatographic Study for Concurrent Determination of
      Canagliflozin and Metformin in Combined Tablets.
AB  - New HPLC-UV method (method A), for simultaneous determination of metformin (MET)
      and canagliflozin (CANA), was developed and compared to another novel UPLC-UV
      method (method B) in their tablet combination. Concerning method A, isocratic
      separation was done by C18 column (100 mm * 2.1 mm, 3 MUm) using methanol and
      0.03 M phosphate buffer (75 : 25, v/v) at pH 3.2 as a mobile phase. Meanwhile,
      chromatographic separation in method B was achieved via Hypersil(r) gold (50 mm *
      2.1 mm, 1.9 MUm). Mobile phase was methanol and 0.03 M phosphate buffer at ratio
      of 80 : 20  v/v. In both, detection was done at wavelength of 240 nm. Method A
      showed satisfactory linearity results over 1-50 MUg.mL-1 and 0.5-100 MUg.mL-1,
      while method B linearity was at 0.1-50 MUg.mL-1 and 0.25-100 MUg.mL-1 for CANA
      and MET, respectively. In terms of accuracy and precision, method A accuracy was
      99.81 +/- 0.73 and 99.37 +/- 0.54, while method B gave accuracy of 99.47 +/- 1.03
      and 99.73 +/- 0.89 for CANA and MET, respectively. For precision, the % RSD was
      found to be less than 2% for three concentrations analyzed three times. The two
      methods are convenient for quality laboratories, yet the UPLC method offered the
      advantage of shorter run times and higher sensitivity.

PMID- 29333317
TI  - Phosphorylated alpha-Synuclein-Copper Complex Formation in the Pathogenesis of
      Parkinson's Disease.
AB  - Parkinson's disease is the second most important neurodegenerative disorder
      worldwide. It is characterized by the presence of Lewy bodies, which are mainly
      composed of alpha-synuclein and ubiquitin-bound proteins. Both the ubiquitin
      proteasome system (UPS) and autophagy-lysosomal pathway (ALS) are altered in
      Parkinson's disease, leading to aggregation of proteins, particularly alpha
      synuclein. Interestingly, it has been observed that copper promotes the protein
      aggregation process. Additionally, phosphorylation of alpha-synuclein along with
      copper also affects the protein aggregation process. The interrelation among
      alpha-synuclein phosphorylation and its capability to interact with copper, with
      the subsequent disruption of the protein degradation systems in the
      neurodegenerative process of Parkinson's disease, will be analyzed in detail in
      this review.

PMID- 29333320
TI  - Our recap for happy new year.

PMID- 29333321
TI  - Periodontal wound healing following reciprocal autologous root transplantation in
      class III furcation defects.
AB  - Purpose: Furcation involvement in the molars is difficult to treat, and has been
      recognized as a risk factor for tooth loss. Although periodontal regenerative
      therapies, including guided tissue regeneration and various types of bone grafts,
      have been applied to furcation defects, the effects of these treatments are
      limited, especially in large class III furcation defects. The purpose of this
      pilot study was to investigate the effect of reciprocal autologous root
      transplantation on periodontal wound healing and regeneration in class III
      furcation defects in dogs. Methods: Furcation defects (7 mm wide and 6 mm high)
      were surgically created after root separation of the unilateral third and fourth
      premolars in 4 dogs. Eight furcation defects were randomized to receive either
      reciprocal autologous root transplantation (test) or no further treatment
      (control). In the test group, the mesial and distal roots were transplanted into
      the distal and mesial extraction sockets, respectively. The animals were
      sacrificed 10 weeks after surgery for histologic evaluation. Results: The healing
      pattern in the control group was characterized by extensive collapse of the flap
      and limited periodontal regeneration. New bone formation in the test group
      (3.56+/-0.57 mm) was significantly greater than in the control group (0.62+/-0.21
      mm). Dense collagen fibers inserting into the residual cementum on the
      transplanted root surfaces were observed in the test group. Slight ankylosis was
      observed in 2 of the 4 specimens in the test group on the mesiodistal sides where
      the root-planed surfaces faced the existing bone. Root resorption (RR) was
      detected in both the control and test groups. Conclusions: Within the limits of
      this study, it can be concluded that reciprocal autologous root transplantation
      was effective for bone regeneration in class III furcation defects in dogs.
      However, further studies are required to standardize the approach in order to
      prevent unwanted RR prior to clinical application.

PMID- 29333322
TI  - A randomized controlled clinical study of periodontal tissue regeneration using
      an extracellular matrix-based resorbable membrane in combination with a
      collagenated bovine bone graft in intrabony defects.
AB  - Purpose: The purpose of this study was to investigate the feasibility of
      regenerative therapy with a collagenated bone graft and resorbable membrane in
      intrabony defects, and to evaluate the effects of the novel extracellular matrix
      (ECM)-based membrane clinically and radiologically. Methods: Periodontal tissue
      regeneration procedure was performed using an ECM-based resorbable membrane in
      combination with a collagenated bovine bone graft in intrabony defects around the
      teeth and implants. A novel extracellular matrix membrane (NEM) and a widely-used
      membrane (WEM) were randomly applied to the test group and the control group,
      respectively. Cone-beam computed tomography images were obtained on the day of
      surgery and 6 months after the procedure. Alginate impressions were taken and
      plaster models were made 1 week and 6 months postoperatively. Results: The
      quantity of bone tissue, the dimensional changes of the surgically treated
      intrabony defects, and the changes in width and height below the grafted bone
      substitutes showed no significant difference between the test and control groups
      at the 6-month examination. Conclusions: The use of NEM for periodontal
      regeneration with a collagenated bovine bone graft showed similar clinical and
      radiologic results to those obtained using WEM.

PMID- 29333323
TI  - Alveolar ridge preservation with an open-healing approach using single-layer or
      double-layer coverage with collagen membranes.
AB  - Purpose: The aim of this prospective pilot study was to compare alveolar ridge
      preservation (ARP) procedures with open-healing approach using a single-layer and
      a double-layer coverage with collagen membranes using radiographic and clinical
      analyses. Methods: Eleven molars from 9 healthy patients requiring extraction of
      the maxillary or mandibular posterior teeth were included and allocated into 2
      groups. After tooth extraction, deproteinized bovine bone mineral mixed with 10%
      collagen was grafted into the socket and covered either with a double-layer of
      resorbable non-cross-linked collagen membranes (DL group, n=6) or with a single
      layer (SL group, n=5). Primary closure was not obtained. Cone-beam computed
      tomography images were taken immediately after the ARP procedure and after a
      healing period of 4 months before implant placement. Radiographic measurements
      were made of the width and height changes of the alveolar ridge. Results: All
      sites healed without any complications, and dental implants were placed at all
      operated sites with acceptable initial stability. The measurements showed that
      the reductions in width at the level 1 mm apical from the alveolar crest
      (including the bone graft) were -1.7+/-0.5 mm in the SL group and -1.8+/-0.4 mm
      in the DL group, and the horizontal changes in the other areas were also similar
      in the DL and SL groups. The reductions in height were also comparable between
      groups. Conclusions: Within the limitations of this study, single-layer and
      double-layer coverage with collagen membranes after ARP failed to show
      substantial differences in the preservation of horizontal or vertical dimensions
      or in clinical healing. Thus, both approaches seem to be suitable for open
      healing ridge preservation procedures.

PMID- 29333324
TI  - Ridge preservation using basic fibroblast growth factor-2 and collagenated
      biphasic calcium phosphate in beagle dogs.
AB  - Purpose: The aim of this study was to evaluate volumetric and histologic changes
      in edentulous alveolar ridge areas after ridge preservation using basic
      fibroblast growth factor-2 (bFGF-2) in combination with collagenated biphasic
      calcium phosphate (BCP). Methods: The experiments were performed in 6 adult male
      beagle dogs. The following 3 groups were created: 1) ridge preservation with bFGF
      2 and collagenated BCP (experimental group), 2) ridge preservation with
      collagenated BCP (positive control group), and 3) a negative control group in
      which no ridge preservation procedure was performed. Volumetric change analysis
      was performed using an optical scanner and casts. Histological observations were
      made using light microscopy. Results: After the initial swelling subsided, the
      magnitude of the volumetric change in the experimental group and positive control
      group was smaller than in the negative control group. In the experimental group,
      a distinct trend was observed for the resorption of residual bone and collagen
      fibers at 4 weeks and for more mature bone and faster healing at 12 weeks.
      Conclusions: Based on the findings of the present study, bFGF-2 may be considered
      for use as a therapeutic molecule in ridge preservation procedures.

PMID- 29333325
TI  - Physicochemical characterization of porcine bone-derived grafting material and
      comparison with bovine xenografts for dental applications.
AB  - Purpose: The physicochemical properties of a xenograft are very important because
      they strongly influence the bone regeneration capabilities of the graft material.
      Even though porcine xenografts have many advantages, only a few porcine
      xenografts are commercially available, and most of their physicochemical
      characteristics have yet to be reported. Thus, in this work we aimed to
      investigate the physicochemical characteristics of a porcine bone grafting
      material and compare them with those of 2 commercially available bovine
      xenografts to assess the potential of xenogenic porcine bone graft materials for
      dental applications. Methods: We used various characterization techniques, such
      as scanning electron microscopy, the Brunauer-Emmett-Teller adsorption method,
      atomic force microscopy, Fourier-transform infrared spectroscopy, X-ray
      diffraction, and others, to compare the physicochemical properties of xenografts
      of different origins. Results: The porcine bone grafting material had relatively
      high porosity (78.4%) and a large average specific surface area (SSA; 69.9 m2/g),
      with high surface roughness (10-point average roughness, 4.47 um) and sub-100-nm
      hydroxyapatite crystals on the surface. Moreover, this material presented a
      significant fraction of sub-100-nm pores, with negligible amounts of residual
      organic substances. Apart from some minor differences, the overall
      characteristics of the porcine bone grafting material were very similar to those
      of one of the bovine bone grafting material. However, many of these
      morphostructural properties were significantly different from the other bovine
      bone grafting material, which exhibited relatively smooth surface morphology with
      a porosity of 62.0% and an average SSA of 0.5 m2/g. Conclusions: Considering that
      both bovine bone grafting materials have been successfully used in oral surgery
      applications in the last few decades, this work shows that the porcine-derived
      grafting material possesses most of the key physiochemical characteristics
      required for its application as a highly efficient xenograft material for bone
      replacement.

PMID- 29333328
TI  - Learning Tree-Structured Detection Cascades for Heterogeneous Networks of
      Embedded Devices.
AB  - In this paper, we present a new approach to learning cascaded classifiers for use
      in computing environments that involve networks of heterogeneous and resource
      constrained, low-power embedded compute and sensing nodes. We present a
      generalization of the classical linear detection cascade to the case of tree
      structured cascades where different branches of the tree execute on different
      physical compute nodes in the network. Different nodes have access to different
      features, as well as access to potentially different computation and energy
      resources. We concentrate on the problem of jointly learning the parameters for
      all of the classifiers in the cascade given a fixed cascade architecture and a
      known set of costs required to carry out the computation at each node. To
      accomplish the objective of joint learning of all detectors, we propose a novel
      approach to combining classifier outputs during training that better matches the
      hard cascade setting in which the learned system will be deployed. This work is
      motivated by research in the area of mobile health where energy efficient real
      time detectors integrating information from multiple wireless on-body sensors and
      a smart phone are needed for real-time monitoring and the delivery of just-in
      time adaptive interventions. We evaluate our framework on mobile sensor-based
      human activity recognition and mobile health detector learning problems.

PMID- 29333326
TI  - Evaluation of the periodontal regenerative properties of patterned human
      periodontal ligament stem cell sheets.
AB  - Purpose: The aim of this study was to determine the effects of patterned human
      periodontal ligament stem cell (hPDLSC) sheets fabricated using a
      thermoresponsive substratum. Methods: In this study, we fabricated patterned
      hPDLSC sheets using nanotopographical cues to modulate the alignment of the cell
      sheet. Results: The hPDLSCs showed rapid monolayer formation on various surface
      pattern widths. Compared to cell sheets grown on flat surfaces, there were no
      significant differences in cell attachment and growth on the nanopatterned
      substratum. However, the patterned hPDLSC sheets showed higher periodontal
      ligamentogenesis-related gene expression in early stages than the unpatterned
      cell sheets. Conclusions: This experiment confirmed that patterned cell sheets
      provide flexibility in designing hPDLSC sheets, and that these stem cell sheets
      may be candidates for application in periodontal regenerative therapy.

PMID- 29333327
TI  - Subcellular western blotting of single cells.
AB  - Although immunoassays are the de facto standard for determining subcellular
      protein localization in individual cells, antibody probe cross-reactivity and
      fixation artifacts remain confounding factors. To enhance selectivity while
      providing single-cell resolution, we introduce a subcellular western blotting
      technique capable of separately assaying proteins in the 14 pL cytoplasm and 2 pL
      nucleus of individual cells. To confer precision fluidic control, we describe a
      passive multilayer microdevice that leverages the rapid transport times afforded
      by miniaturization. After isolating single cells in microwells, we apply single
      cell differential detergent fractionation to lyse and western blot the
      cytoplasmic lysate, whereas the nucleus remains intact in the microwell.
      Subsequently, we lyse the intact nucleus and western blot the nuclear lysate. To
      index each protein analysis to the originating subcellular compartment, we
      utilize bi-directional electrophoresis, a multidimensional separation that assays
      the lysate from each compartment in a distinct region of the separation axis.
      Single-cell bi-directional electrophoresis eliminates the need for semi
      subjective image segmentation algorithms required in immunocytochemistry. The
      subcellular, single-cell western blot is demonstrated for six targets per cell,
      and successfully localizes spliceosome-associated proteins solubilized from large
      protein and RNA complexes, even for closely sized proteins (a 7 kDa difference).
      Measurement of NF-kappaB translocation dynamics in unfixed cells at 15-min
      intervals demonstrates reduced technical variance compared with
      immunofluorescence. This chemical cytometry assay directly measures the
      nucleocytoplasmic protein distribution in individual unfixed cells, thus
      providing insight into protein signaling in heterogeneous cell populations.

PMID- 29333329
TI  - Stable Pd-Doped Ceria Structures for CH4 Activation and CO Oxidation.
AB  - Doping CeO2 with Pd atoms has been associated with catalytic CO oxidation, but
      current surface models do not allow CO adsorption. Here, we report a new
      structure of Pd-doped CeO2(111), in which Pd adopts a square planar configuration
      instead of the previously assumed octahedral configuration. Oxygen removal from
      this doped structure is favorable. The resulting defective Pd-doped CeO2 surface
      is active for CO oxidation and is also able to cleave the first C-H bond in
      methane. We show how the moderate CO adsorption energy and dynamic features of
      the Pd atom upon CO adsorption and CO oxidation contribute to a low-barrier
      catalytic cycle for CO oxidation. These structures, which are also observed for
      Ni and Pt, can lead to a more open coordination environment around the doped
      transition-metal center. These thermally stable structures are relevant to the
      development of single-atom catalysts.

PMID- 29333330
TI  - Amorphous Cobalt Vanadium Oxide as a Highly Active Electrocatalyst for Oxygen
      Evolution.
AB  - The water-splitting reaction provides a promising mechanism to store renewable
      energies in the form of hydrogen fuel. The oxidation half-reaction, the oxygen
      evolution reaction (OER), is a complex four-electron process that constitutes an
      efficiency bottleneck in water splitting. Here we report a highly active OER
      catalyst, cobalt vanadium oxide. The catalyst is designed on the basis of a
      volcano plot of metal-OH bond strength and activity. The catalyst can be
      synthesized by a facile hydrothermal route. The most active pure-phase material
      (a-CoVO x ) is X-ray amorphous and provides a 10 mA cm-2 current density at an
      overpotential of 347 mV in 1 M KOH electrolyte when immobilized on a flat
      substrate. The synthetic method can also be applied to coat a high-surface-area
      substrate such as nickel foam. On this three-dimensional substrate, the a-CoVO x
      catalyst is highly active, reaching 10 mA cm-2 at 254 mV overpotential, with a
      Tafel slope of only 35 mV dec-1. This work demonstrates a-CoVO x as a promising
      electrocatalyst for oxygen evolution and validates M-OH bond strength as a
      practical descriptor in OER catalysis.

PMID- 29333331
TI  - Single-impulse Panoramic Photoacoustic Computed Tomography of Small-animal Whole
      body Dynamics at High Spatiotemporal Resolution.
AB  - Imaging of small animals has played an indispensable role in preclinical research
      by providing high dimensional physiological, pathological, and phenotypic
      insights with clinical relevance. Yet pure optical imaging suffers from either
      shallow penetration (up to ~1-2 mm) or a poor depth-to-resolution ratio (~1/3),
      and non-optical techniques for whole-body imaging of small animals lack either
      spatiotemporal resolution or functional contrast. Here, we demonstrate that
      standalone single-impulse photoacoustic computed tomography (SIP-PACT) mitigates
      these limitations by combining high spatiotemporal resolution (125-um in-plane
      resolution, 50 us / frame data acquisition and 50-Hz frame rate), deep
      penetration (48-mm cross-sectional width in vivo), anatomical, dynamical and
      functional contrasts, and full-view fidelity. By using SIP-PACT, we imaged in
      vivo whole-body dynamics of small animals in real time and obtained clear sub
      organ anatomical and functional details. We tracked unlabeled circulating
      melanoma cells and imaged the vasculature and functional connectivity of whole
      rat brains. SIP-PACT holds great potential for both pre-clinical imaging and
      clinical translation.

PMID- 29333333
TI  - 'Her body [was] like a hard-worked machine': Women's work and disability in
      coalfields literature, 1880-1950.
AB  - This essay considers the representation of women's work and disability in British
      coalfields literature in the period 1880-1950. Industrial settings are a rich
      source for literature concerned with bodily health, injury and disability and
      offer insights into the gendering of the working body whether male or female.
      Situating this largely realist body of novels, stories and plays in its
      historical context, this article will focus on intersections between work, class
      and gender. It shows how the vital, but unpaid, work of women in domestic labour
      was depicted as an extension of the industrial machine, which had clear
      consequences in terms of high mortality and morbidity rates amongst women.

PMID- 29333334
TI  - The Effect of the 2012 ASCCP Consensus Guideline for Abnormal Cervical Cytology
      on Resident Colposcopy Training.
AB  - The primary objective was to determine the theoretical number of colposcopies at
      a resident clinic if the 2012 American Society for Colposcopy and Cervical
      Pathology (ASCCP) guidelines were applied. The secondary objective was to
      determine the actual number of colposcopies before and after the ASCCP
      guidelines. This was a two-part descriptive study. The first part applied the
      2012 ASCCP guidelines to all pre-guideline colposcopy cases at a single resident
      clinic. These theoretical results were then compared to the actual number of
      colposcopies. The second part compared the actual number of colposcopies during
      the one-year time period before and after the guidelines. Chi-Square tests and
      Fisher's Exact tests were used to examine the association of categorical
      variables. Seventy-three colposcopies were performed during the pre-guideline
      period. After applying the 2012 ASCCP guidelines, 52.1% would not have been
      indicated, resulting in 35 colposcopies. The largest reductions would have
      occurred in patients with low grade cytologic abnormalities. Applying the new
      guidelines, patients 24 years and younger would have been less likely than
      patients ages 25 to 64 to require colposcopy (P<.001). Fifty-eight indicated
      colposcopies were actually performed during the post-guideline period. While
      there was a decrease in the number of colposcopies performed post-guidelines, the
      decrease was not as dramatic as expected. From a training standpoint, as
      indications for colposcopy decrease, fewer training opportunities are available
      for residents. In particular, residents will have less experience evaluating low
      grade cytologic abnormalities in younger women.

PMID- 29333335
TI  - Recommendations for Contraception: Examining the Role of Patients' Age and Race.
AB  - The literature suggests that women of different races are more or less likely to
      use certain contraceptive methods and patient race can influence which
      contraceptive recommendations a provider makes. To explore whether health care
      providers treat individuals of different races differently, we conducted a
      preliminary investigation on whether medical students recommended different
      contraceptive methods for hypothetical patients presenting with the same clinical
      features who only varied by race. Third- and fourth-year medical students (n=103)
      at the University of Hawai'i completed an online survey. Students read case
      studies about a 23-year-old and 36-year-old patient and then made contraceptive
      recommendations. All students reviewed the same scenarios, with the exception of
      the patient's name which was randomly assigned to represent one of five
      racial/ethnic groups (White, Chinese, Filipina, Native Hawaiian, and
      Micronesian). Recommendations were analyzed using chi2 tests and bivariate
      logistic regressions. For the younger patient, students were most likely to
      recommend intrauterine devices (IUDs), followed by the contraceptive pill and
      Etonogestrel implant; recommendations did not differ by race/ethnicity (P = .91).
      For the older patient, students were most likely to recommend IUDs or
      sterilization, and Micronesian women were more likely to receive sterilization
      recommendations compared to White women (60% versus 27%, P = .04). In summary,
      contraceptive recommendations, specifically the frequency of recommending
      sterilization varied by race. Our findings add to the literature exploring the
      role of a patient's race/ethnicity on recommendations for contraception and
      highlights the need for more studies exploring the etiology of health care
      disparities.

PMID- 29333336
TI  - Medical School Hotline: School of Medicine Departments - Year in Review 2017,
      Part 1.

PMID- 29333332
TI  - Next Generation Tissue Engineering of Orthopedic Soft Tissue-to-Bone Interfaces.
AB  - Soft tissue-to-bone interfaces are complex structures that consist of gradients
      of extracellular matrix materials, cell phenotypes, and biochemical signals.
      These interfaces, called entheses for ligaments, tendons, and the meniscus, are
      crucial to joint function, transferring mechanical loads and stabilizing
      orthopedic joints. When injuries occur to connected soft tissue, the enthesis
      must be re-established to restore function, but due to structural complexity,
      repair has proven challenging. Tissue engineering offers a promising solution for
      regenerating these tissues. This prospective review discusses methodologies for
      tissue engineering the enthesis, outlined in three key design inputs: materials
      processing methods, cellular contributions, and biochemical factors.

PMID- 29333337
TI  - Insights in Public Health: Stepping Up Vector Control's Program Capacity To
      Prevent Arboviral Disease Transmission in Hawai'i.

PMID- 29333339
TI  - Time multiplexed deep reactive ion etching of germanium and silicon-A comparison
      of mechanisms and application to x-ray optics.
AB  - Although the mechanisms of deep reactive ion etching (DRIE) of silicon have been
      reported extensively, very little by comparison has been discussed concerning
      DRIE of germanium. By directly comparing silicon and germanium etching in a time
      multiplexed DRIE process, the authors extract significant differences in etch
      mechanisms from a design of experiment and discuss how these differences are
      relevant to the design and fabrication of silicon and germanium collimating
      channel array x-ray optics. The differences are illuminated by characteristics
      such as reactive ion etching (RIE)-lag, aspect ratio dependent etching, and
      sidewall passivation. Specifically, the authors demonstrate the more severe
      nature of RIE-lag in germanium, especially at aspect ratios exceeding 13:1. In
      addition, the differences in the profile evolution between silicon and germanium
      are shown to be a result of differences in sidewall passivation. There is also a
      correlation between the different sidewall passivation and the inherent lack of
      scalloping in the case of germanium DRIE.

PMID- 29333340
TI  - Examining differences in HPV awareness and knowledge and HPV vaccine awareness
      and acceptability between U.S. Hispanic and island Puerto Rican women.
AB  - Background: In 2015, only 42% of Puerto Rican (PR) girls aged 13-17 and 44% of
      U.S. Hispanic girls aged 13-17 were vaccinated with all three Human
      Papillomavirus (HPV) vaccine doses; These percentages were far lower than the
      Healthy People 2020 goal of 80% of girls aged 13-15 the Healthy People 2020 goal
      of 80%. The purpose of this study was to examine potential differences in HPV
      awareness and knowledge and HPV vaccine awareness and acceptability between a
      population-based sample of U.S. Hispanic and island Puerto Rican women. Methods:
      We restricted our analyses to female respondents from the Health Information
      National Trends Survey (HINTS) 2007 (n=375; U.S. Hispanic) and HINTS Puerto Rico
      2009 (n=417; PR). Using the Wald chi-square test, we assessed if there were
      significant differences in HPV awareness and knowledge and HPV vaccine awareness
      and acceptability between U.S. Hispanic and island PR women. We then utilized
      logistic or multinomial regression to control for covariates on significant
      outcomes. Results: Both groups of Hispanic women were highly knowledgeable that
      HPV causes cancer (89.2% in both samples) and that HPV is a sexually transmitted
      infection (78.1% [U.S. Hispanics] and 84.7% [PR]). Less than 10% of both groups
      recognized that HPV can clear on its own without treatment. Island PR women had
      significantly higher HPV vaccine awareness (66.9% vs. 61.0%; Wald X2 F(1, 97) =
      16.03, p < .001) and were more accepting of the HPV vaccine for a real or
      hypothetical daughter, compared to U.S. Hispanic women (74.8% vs. 56.1%; Wald X2
      F(2, 96) = 7.18, p < .001). However, after controlling for sociodemographic
      variables and survey group, there was no longer a difference between the two
      groups of women and HPV vaccine awareness (AOR = .53; 95% CI = .23, 1.24).
      Moreover, after controlled analysis, island PR women were significantly less
      likely to have their hypothetical daughter get the HPV vaccine, compared to U.S.
      Hispanic women (AOR = 0.26; 95% CI = .08, .81). Conclusions: Future research
      focused on factors contributing to differences and similarities in HPV knowledge
      and awareness and HPV vaccine awareness and acceptability between these two
      groups of Hispanic women is warranted. Findings may assist in developing health
      education programs and media to promote HPV vaccination among both groups.

PMID- 29333341
TI  - Preventive effects of Salvia officinalis leaf extract on insulin resistance and
      inflammation in a model of high fat diet-induced obesity in mice that responds to
      rosiglitazone.
AB  - Background: Salvia officinalis (sage) is a native plant to the Mediterranean
      region and has been used for a long time in traditional medicine for various
      diseases. We investigated possible anti-diabetic, anti-inflammatory and anti
      obesity effects of sage methanol (MetOH) extract in a nutritional mouse model of
      obesity, inflammation and insulin resistance, as well as its effects on lipolysis
      and lipogenesis in 3T3-L1 cells. Methods: Diet-induced obese (DIO) mice were
      treated for five weeks with sage methanol extract (100 and 400 mg kg-1/day bid),
      or rosiglitazone (3 mg kg-1/day bid), as a positive control. Energy expenditure,
      food intake, body weight, fat mass, liver glycogen and lipid content were
      evaluated. Blood glucose, and plasma levels of insulin, lipids leptin and pro-
      and anti-inflammatory cytokines were measured throughout the experiment. The
      effects of sage MetOH extract on lipolysis and lipogenesis were tested in vitro
      in 3T3-L1 cells. Results: After two weeks of treatment, the lower dose of sage
      MetOH extract decreased blood glucose and plasma insulin levels during an oral
      glucose tolerance test (OGTT). An insulin tolerance test (ITT), performed at day
      29 confirmed that sage improved insulin sensitivity. Groups treated with low dose
      sage and rosiglitazone showed very similar effects on OGTT and ITT. Sage also
      improved HOMA-IR, triglycerides and NEFA. Treatment with the low dose increased
      the plasma levels of the anti-inflammatory cytokines IL-2, IL-4 and IL-10 and
      reduced the plasma level of the pro-inflammatory cytokines IL-12, TNF-alpha, and
      KC/GRO. The GC analysis revealed the presence of two PPARs agonist in sage MetOH
      extract. In vitro, the extract reduced in a dose-related manner the accumulation
      of lipid droplets; however no effect on lipolysis was observed. Conclusions: Sage
      MetOH extract at low dose exhibits similar effects to rosiglitazone. It improves
      insulin sensitivity, inhibits lipogenesis in adipocytes and reduces inflammation
      as judged by plasma cytokines. Sage presents an alternative to pharmaceuticals
      for the treatment of diabetes and associated inflammation.

PMID- 29333342
TI  - Is there a link between aging and microbiome diversity in exceptional mammalian
      longevity?
AB  - A changing microbiome has been linked to biological aging in mice and humans,
      suggesting a possible role of gut flora in pathogenic aging phenotypes. Many bat
      species have exceptional longevity given their body size and some can live up to
      ten times longer than expected with little signs of aging. This study explores
      the anal microbiome of the exceptionally long-lived Myotis myotis bat,
      investigating bacterial composition in both adult and juvenile bats to determine
      if the microbiome changes with age in a wild, long-lived non-model organism,
      using non-lethal sampling. The anal microbiome was sequenced using metabarcoding
      in more than 50 individuals, finding no significant difference between the
      composition of juvenile and adult bats, suggesting that age-related microbial
      shifts previously observed in other mammals may not be present in Myotis myotis.
      Functional gene categories, inferred from metabarcoding data, expressed in the M.
      myotis microbiome were categorized identifying pathways involved in metabolism,
      DNA repair and oxidative phosphorylation. We highlight an abundance of
      'Proteobacteria' relative to other mammals, with similar patterns compared to
      other bat microbiomes. Our results suggest that M. myotis may have a relatively
      stable, unchanging microbiome playing a role in their extended 'health spans'
      with the advancement of age, and suggest a potential link between microbiome and
      sustained, powered flight.

PMID- 29333343
TI  - Resounding failure to replicate links between developmental language disorder and
      cerebral lateralisation.
AB  - Background: It has been suggested that failure to establish cerebral
      lateralisation may be related to developmental language disorder (DLD). There has
      been weak support for any link with handedness, but more consistent reports of
      associations with functional brain lateralisation for language. The consistency
      of lateralisation across different functions may also be important. We aimed to
      replicate previous findings of an association between DLD and reduced laterality
      on a quantitative measure of hand preference (reaching across the midline) and on
      language laterality assessed using functional transcranial Doppler ultrasound
      (fTCD). Methods: From a sample of twin children aged from 6;0 to 11;11 years, we
      identified 107 cases of DLD and 156 typically-developing comparison cases for
      whom we had useable data from fTCD yielding a laterality index (LI) for language
      function during an animation description task. Handedness data were also
      available for these children. Results: Indices of handedness and language
      laterality for this twin sample were similar to those previously reported for
      single-born children. There were no differences between the DLD and TD groups on
      measures of handedness or language lateralisation, or on a categorical measure of
      consistency of left hemisphere dominance. Contrary to prediction, there was a
      greater incidence of right lateralisation for language in the TD group (19.90%)
      than the DLD group (9.30%), confirming that atypical laterality is not
      inconsistent with typical language development. We also failed to replicate
      associations between language laterality and language test scores. Discussion and
      Conclusions: Given the large sample studied here and the range of measures, we
      suggest that previous reports of atypical manual or language lateralisation in
      DLD may have been false positives.

PMID- 29333344
TI  - The old and the new plankton: ecological replacement of associations of mollusc
      plankton and giant filter feeders after the Cretaceous?
AB  - Owing to their great diversity and abundance, ammonites and belemnites
      represented key elements in Mesozoic food webs. Because of their extreme
      ontogenetic size increase by up to three orders of magnitude, their position in
      the food webs likely changed during ontogeny. Here, we reconstruct the number of
      eggs laid by large adult females of these cephalopods and discuss developmental
      shifts in their ecologic roles. Based on similarities in conch morphology, size,
      habitat and abundance, we suggest that similar niches occupied in the Cretaceous
      by juvenile ammonites and belemnites were vacated during the extinction and later
      partially filled by holoplanktonic gastropods. As primary consumers, these
      extinct cephalopod groups were important constituents of the plankton and a
      principal food source for planktivorous organisms. As victims or, respectively,
      profiteers of this case of ecological replacement, filter feeding chondrichthyans
      and cetaceans likely filled the niches formerly occupied by large pachycormid
      fishes during the Jurassic and Cretaceous.

PMID- 29333345
TI  - Ontogeny reversal and phylogenetic analysis of Turritopsis sp.5 (Cnidaria,
      Hydrozoa, Oceaniidae), a possible new species endemic to Xiamen, China.
AB  - Ontogeny reversal, as seen in some cnidarians, is an unprecedented phenomenon in
      the animal kingdom involving reversal of the ordinary life cycle. Three species
      of Turritopsis have been shown to be capable of inverted metamorphosis, a process
      in which the pelagic medusa transforms back into a juvenile benthic polyp stage
      when faced with adverse conditions. Turritopsis sp.5 is a species of Turritopsis
      collected from Xiamen, China which presents a similar ability, being able to
      reverse its life cycle if injured by mechanical stress. Phylogenetic analysis
      based on both 16S rDNA and cytochrome c oxidase subunit I (COI) genetic barcodes
      shows that Turritopsis sp.5 is phylogenetically clustered in a clade separate
      from other species of Turritopsis. The genetic distance between T. sp.5 and the
      Japanese species T. sp.2 is the shortest, when measured by the Kimura 2-Parameter
      metric, and the distance to the New Zealand species T. rubra is the largest. An
      experimental assay on the induction of reverse development in this species was
      initiated by cutting medusae into upper and lower parts. We show, for the first
      time, that the two dissected parts have significantly different potentials to
      transform into polyps. Also, a series of morphological changes of the reversed
      life cycle can be recognised, including medusa stage, contraction stage I,
      contraction stage II, cyst, cyst with stolons, and polyp. The discovery of
      species capable of reverse ontogeny caused by unfavorable conditions adds to the
      available systems with which to study the cell types that contribute to the
      developmental reversal and the molecular mechanisms of the directional
      determination of ontogeny.

PMID- 29333346
TI  - Boundaries in ground beetle (Coleoptera: Carabidae) and environmental variables
      at the edges of forest patches with residential developments.
AB  - Background: Few studies of edge effects on wildlife objectively identify habitat
      edges or explore non-linear responses. In this paper, we build on ground beetle
      (Coleoptera: Carabidae) research that has begun to address these domains by using
      triangulation wombling to identify boundaries in beetle community structure and
      composition at the edges of forest patches with residential developments. We
      hypothesized that edges are characterized by boundaries in environmental
      variables that correspond to marked discontinuities in vegetation structure
      between maintained yards and forest. We expected environmental boundaries to be
      associated with beetle boundaries. Methods: We collected beetles and measured
      environmental variables in 200 m by 200 m sampling grids centered at the edges of
      three forest patches, each with a rural, suburban, or urban context, in
      Charlotte, North Carolina, USA. We identified boundaries within each grid at two
      spatial scales and tested their significance and overlap using boundary
      statistics and overlap statistics, respectively. We complemented boundary
      delineation with k-means clustering. Results: Boundaries in environmental
      variables, such as temperature, grass cover, and leaf litter depth, occurred at
      or near the edges of all three sites, in many cases at both scales. The beetle
      variables that exhibited the most pronounced boundary structure in relation to
      edges were total species evenness, generalist abundance, generalist richness,
      generalist evenness, and Agonum punctiforme abundance. Environmental and beetle
      boundaries also occurred within forest patches and residential developments,
      indicating substantial localized spatial variation on either side of edges.
      Boundaries in beetle and environmental variables that displayed boundary
      structure at edges significantly overlapped, as did boundaries on either side of
      edges. The comparison of boundaries and clusters revealed that boundaries formed
      parts of the borders of patches of similar beetle or environmental condition.
      Discussion: We show that edge effects on ground beetle community structure and
      composition and environmental variation at the intersection of forest patches and
      residential developments can be described by boundaries and that these boundaries
      overlap in space. However, our results also highlight the complexity of edge
      effects in our system: environmental boundaries were located at or near edges
      whereas beetle boundaries related to edges could be spatially disjunct from them;
      boundaries incompletely delineated edges such that only parts of edges were well
      described by sharp transitions in beetle and/or environmental variables; and the
      occurrence of boundaries related to edges was apparently influenced by individual
      property management practices, site-specific characteristics such as development
      geometry, and spatial scale.

PMID- 29333347
TI  - Beyond harm's reach? Submersion of river turtle nesting areas and implications
      for restoration actions after Amazon hydropower development.
AB  - The global expansion of energy demands combined with abundant rainfall, large
      water volumes and high flow in tropical rivers have led to an unprecedented
      expansion of dam constructions in the Amazon. This expansion generates an urgent
      need for refined approaches to river management; specifically a move away from
      decision-making governed by overly generalized guidelines. For the first time we
      quantify direct impacts of hydropower reservoir establishment on an Amazon fresh
      water turtle. We conducted surveys along 150 km of rivers upstream of a new dam
      construction during the low water months that correspond to the nesting season of
      Podocnemis unifilis in the study area. Comparison of nest-areas before (2011,
      2015) and after (2016) reservoir filling show that reservoir impacts extend 13%
      beyond legally defined limits. The submerged nesting areas accounted for a total
      of 3.8 ha of nesting habitat that was inundated as a direct result of the
      reservoir filling in 2016. Our findings highlight limitations in the development
      and implementation of existing Brazilian environmental impact assessment process.
      We also propose potential ways to mitigate the negative impacts of dams on
      freshwater turtles and the Amazonian freshwater ecosystems they inhabit.

PMID- 29333348
TI  - A new species of Cretalamna sensu stricto (Lamniformes, Otodontidae) from the
      Late Cretaceous (Santonian-Campanian) of Alabama, USA.
AB  - Decades of collecting from exposures of the Upper Cretaceous Tombigbee Sand
      Member of the Eutaw Formation and Mooreville Chalk in Alabama, USA has produced
      large numbers of isolated Cretalamna (sensu stricto) teeth. Many of these teeth
      had formerly been assigned to the extinct Late Cretaceous shark Cretalamna
      appendiculata (Agassiz, 1843), a taxon that is now considered largely restricted
      to the Turonian of Europe. Recent studies have shed light on the diversity of
      Late Cretaceous Cretalamna (s.s.) taxa, and here we recognize a new species from
      Alabama, Cretalamna bryanti. The teeth of C. bryanti sp. nov. appear aligned with
      the members of the Cretalamna borealis species group, but can be distinguished
      from these other species by a combination of the following: anterior teeth with a
      more pronounced and triangular lingual root protuberance, broader triangular
      cusp, and a taller root relative to the height of the crown; anteriorly situated
      lateroposterior teeth have a distally inclined or hooked main cusp and more than
      one pair of lateral cusplets; and lateroposterior teeth have a strong distally
      hooked main cusp and a root that is largely symmetrical in basal view. At
      present, C. bryanti sp. nov. is stratigraphically confined to the
      Santonian/Campanian Dicarinella asymetrica Sigal, 1952 and Globotruncanita
      elevata Brotzen, 1934 Planktonic Foraminiferal Zones within the Tombigbee Sand
      Member of the Eutaw Formation and Mooreville Chalk, and teeth have been collected
      from only four counties in central and western Alabama. The recognition of C.
      bryanti sp. nov. in Alabama adds to our knowledge on the diversity and
      distribution of Late Cretaceous otodontids in the region.

PMID- 29333349
TI  - Annual and spatial variation in composition and activity of terrestrial mammals
      on two replicate plots in lowland forest of eastern Ecuador.
AB  - Terrestrial mammals are important components of lowland forests in Amazonia (as
      seed dispersal agents, herbivores, predators) but there are relatively few
      detailed studies from areas that have not been affected by human activities
      (e.g., hunting, logging). Yet, such information is needed to evaluate effects of
      humans elsewhere. We used camera traps to sample medium to large-sized
      terrestrial mammals at a site in lowland forests of eastern Ecuador, one of the
      most biologically rich areas in the world. We deployed cameras on two study plots
      in terra firme forest at Tiputini Biodiversity Station. Sixteen cameras were
      arranged 200 m apart in a 4 * 4 grid on each plot. Cameras were operated for  60
      days in January-March, 2014-2017, for a total of 3,707 and 3,482 trap-days on the
      two plots (Harpia, Puma). A total of 28 species were recorded; 26 on Harpia and
      25 on Puma. Number of species recorded each year was slightly greater on Harpia
      whereas overall capture rates (images/100 trap-days) were higher on Puma.
      Although most species were recorded on each plot, differences in capture rates
      meant that yearly samples on a given plot were more similar to each other than to
      samples on the other plot. Images of most species showed a clumped distribution
      pattern on each plot; Panthera onca was the only species that did not show a
      clumped distribution on either plot. Images at a given camera location showed no
      evidence of autocorrelation with numbers of images at nearby camera locations,
      suggesting that species were responding to small-scale differences in habitat
      conditions. A redundancy analysis showed that environmental features within 50 or
      100 m of camera locations (e.g., elevation, variation in elevation, slope,
      distance to streams) accounted for significant amounts of variation in
      distribution patterns of species. Composition and relative importance based on
      capture rates were very similar to results from cameras located along trails at
      the same site; similarities decreased at increasing spatial scales based on
      comparisons with results from other sites in Ecuador and Peru.

PMID- 29333350
TI  - Scale-up of a Luminescent Solar Concentrator-Based Photomicroreactor via
      Numbering-up.
AB  - The use of solar energy to power chemical reactions is a long-standing dream of
      the chemical community. Recently, visible-light-mediated photoredox catalysis has
      been recognized as the ideal catalytic transformation to convert solar energy
      into chemical bonds. However, scaling photochemical transformations has been
      extremely challenging due to Bouguer-Lambert-Beer law. Recently, we have
      pioneered the development of luminescent solar concentrator photomicroreactors
      (LSC-PMs), which display an excellent energy efficiency. These devices harvest
      solar energy, convert the broad solar energy spectrum to a narrow-wavelength
      region, and subsequently waveguide the re-emitted photons to the reaction
      channels. Herein, we report on the scalability of such LSC-PMs via a numbering-up
      strategy. Paramount in our work was the use of molds that were fabricated via 3D
      printing. This allowed us to rapidly produce many different prototypes and to
      optimize experimentally key design aspects in a time-efficient fashion. Reactors
      up to 32 parallel channels have been fabricated that display an excellent flow
      distribution using a bifurcated flow distributor (standard deviations below 10%).
      This excellent flow distribution was crucial to scale up a model reaction
      efficiently, displaying yields comparable to those obtained in a single-channel
      device. We also found that interchannel spacing is an important and unique design
      parameter for numbered-up LSC-PMs, which influences greatly the photon flux
      experienced within the reaction channels.

PMID- 29333351
TI  - Understanding the Effect of the Dianhydride Structure on the Properties of
      Semiaromatic Polyimides Containing a Biobased Fatty Diamine.
AB  - In this work we report the effect of the hard block dianhydride structure on the
      overall properties of partially biobased semiaromatic polyimides. For the study,
      four polyimides were synthesized using aliphatic fatty dimer diamine (DD1) as the
      soft block and four different commercially available aromatic dianhydrides as the
      hard block: 4,4'-(4,4'-isopropylidenediphenoxy) bis(phthalic anhydride) (BPADA),
      4,4'-oxidiphthalic anhydride (ODPA), 4,4'-(Hexafluoroisopropylidene) diphthalic
      anhydride (6FDA), and 3,3',4,4'-biphenyltetracarboxylic dianhydride (BPDA). The
      polymers synthesized were fully organo-soluble thermoplastic branched polyimides
      with glass transition temperatures close to room temperature. The detailed
      analysis took into account several aspects of the dianhydrides structure
      (planarity, rigidity, bridging group between the phtalimides, and electronic
      properties) and related them to the results obtained by differential scanning
      calorimetry, rheology, fluorescence and broadband dielectric spectroscopy.
      Moreover, the effects of physical parameters (crystallization and electronic
      interactions) on the relaxation behavior are discussed. Despite the presence of
      the bulky branched soft block given by the dimer diamine, all polyimides showed
      intermolecular charge transfer complexes, whose extent depends on the electronic
      properties of the dianhydride hard block. Furthermore, the results showed that
      polyimides containing flexible and bulky hard blocks turned out fully amorphous
      while the more rigid dianhydride (BPDA) led to a nanophase separated morphology
      with low degree of crystallinity resulting in constrained segmental relaxation
      with high effect on its mechanical response with the annealing time. This work
      represents the first detailed report on the development and characterization of
      polyimides based on a biobased fatty dimer diamine. The results highlight the
      potential of polymer property design by controlled engineering of the aromatic
      dianhydride blocks.

PMID- 29333352
TI  - Smartphone-Based Point-of-Care Urinalysis Under Variable Illumination.
AB  - Urine tests are performed by using an off-the-shelf reference sheet to compare
      the color of test strips. However, the tabular representation is difficult to use
      and more prone to visual errors, especially when the reference color-swatches to
      be compared are spatially apart. Thus, making it is difficult to distinguish
      between the subtle differences of shades on the reagent pads. This manuscript
      represents a new arrangement of reference arrays for urine test strips
      (urinalysis). Reference color swatches are grouped in a doughnut chart,
      surrounding each reagent pad on the strip. The urine test can be evaluated using
      naked eye by referring to the strip with no additional sheet necessary. Along
      with this new strip, an algorithm for smartphone based application is also
      proposed as an alternative to deliver diagnostic results. The proposed
      colorimetric detection method evaluates the captured image of the strip, under
      various color spaces and evaluates ten different tests for urine. Thus, the
      proposed system can deliver results on the spot using both naked eye and
      smartphone. The proposed scheme delivered accurate results under various
      environmental illumination conditions without any calibration requirements,
      exhibiting performances suitable for real-life applications and an ease for a
      common user.

PMID- 29333353
TI  - Spine Stereotactic Body Radiation Therapy Residual Setup Errors and Intra
      Fraction Motion Using the Stereotactic X-Ray Image Guidance Verification System.
AB  - Purpose: To determine the precision of our institution's current immobilization
      devices for spine SBRT, ultimately leading to recommendations for appropriate
      planning margins. Methods: We identified 12 patients (25 treatments) with spinal
      metastasis treated with spine Stereotactic Body Radiation Therapy (SBRT). The
      Body-FIX system was used as immobilization device for thoracic (T) and lumbar (L)
      spine lesions. The head and shoulder mask system was used as immobilization
      device for cervical (C) spine lesions. Initial patient setup used the infrared
      positioning system with body markers. Stereotactic X-ray imaging was then
      performed and correction was made if the initial setup error exceeded
      predetermined institutional tolerances, 1.5 mm for translation and 2 degrees  for
      rotation. Three additional sets of verification X-rays were obtained pre-, mid-,
      and post-treatment for all treatments. Results: Intrafraction motion regardless
      of immobilization technique was found to be 1.28 +/- 0.57 mm. The mean and
      standard deviation of the variances along each direction were as follows:
      Superior-inferior, 0.56 +/- 0.39 mm and 0.77 +/- 0.52 mm, (p = 0.25); Anterior
      posterior, 0.57 +/- 0.43 mm and 1.14 +/- 0.61 mm, (p = 0.01); Left-right, 0.48 +/
      0.34 mm and 0.74 +/- 0.40 mm, (p = 0.09) respectively. There was a significantly
      greater difference in the average 3D variance of the BodyFIX as compared to the
      head and shoulder mask immobilization system, 1.04 +/- 0.46 mm and 1.71 +/- 0.52
      mm; (p = 0.003) respectively. Conclusions: Overall, our institution's image
      guidance system using stereotactic X-ray imaging verification provides acceptable
      localization accuracy as previously defined in the literature. We observed a
      greater intrafraction motion for the head and shoulder mask as compared with the
      BodyFIX immobilization system, which may be a result of greater C-spine mobility
      and/or the suboptimal mask immobilization. Thus, better immobilization techniques
      for C-spine SBRT are needed to reduce setup error and intrafraction motion. We
      are currently exploring alternative C-spine immobilization techniques to improve
      set up accuracy and decrease intrafraction motion during treatment.

PMID- 29333354
TI  - Novel Wavelet-Based Segmentation of Prostate CBCT Images with Implanted Calypso
      Transponders.
AB  - Segmentation of prostate Cone Beam CT (CBCT) images is an essential step towards
      real-time adaptive radiotherapy (ART). It is challenging for Calypso patients, as
      more artifacts generated by the beacon transponders are present on the images. We
      herein propose a novel wavelet-based segmentation algorithm for rectum, bladder,
      and prostate of CBCT images with implanted Calypso transponders. For a given
      CBCT, a Moving Window-Based Double Haar (MWDH) transformation is applied first to
      obtain the wavelet coefficients. Based on a user defined point in the object of
      interest, a cluster algorithm based adaptive thresholding is applied to the low
      frequency components of the wavelet coefficients, and a Lee filter theory based
      adaptive thresholding is applied on the high frequency components. For the next
      step, the wavelet reconstruction is applied to the thresholded wavelet
      coefficients. A binary (segmented) image of the object of interest is therefore
      obtained. 5 hypofractionated Calypso prostate patients with daily CBCT were
      studied. DICE, Sensitivity, Inclusiveness and DeltaV were used to evaluate the
      segmentation result.

PMID- 29333355
TI  - Bilateral Peripheral Nerve Field Stimulation for Intractable Coccygeal Pain: A
      Case Study Using Dual Lead Intercommunication.
AB  - Coccygeal pain is a difficult chronic pain problem with mixed response to various
      treatments. This is a report of a case of coccygeal pain that after failing
      various conservative and interventional procedures over five years was evaluated
      with a temporary peripheral sacral fascial lead followed by implantation of
      bilateral sacral paramedian leads for peripheral nerve field stimulation (PNFS).
      This resulted in marked pain control and resumption of full activity. The visual
      analog scale (VAS) pain score improved from eight pre-implant to one after
      implant and has remained at that level in follow-up. Peripheral nerve field
      stimulation has been reported for axial chronic back pain, post-laminectomy pain
      and sacroiliac joint pain either alone or in conjunction with epidural spinal
      cord stimulation. Both single and parallel leads have been used to provide wider
      stimulation but differences in location have not been examined. This is the first
      case report of the use of PNFS for treatment of intractable chronic coccygeal
      pain. The effectiveness of PNFS was established for this patient by using a
      prolonged 10-day temporary trial period followed by a 30-day interval without
      stimulation during which the pain returned to the pre-trial level before
      proceeding with permanent implantation, it was clear that in this case, PNFS was
      effective for pain control. Interestingly, the trial and permanent leads were
      both in the posterior sacral fascia but not in identical positions yet equally
      effective for pain control. The observation of the effectiveness of different
      positions may indicate that at least for peripheral field stimulation there may
      be significant current spread in the fascia. Two and three months after the
      implant, we examined the effect of different lead settings and the effect of
      unilateral stimulation compared with bilateral stimulation with and without
      interlead communication. The patient feedback in this case provides some
      understanding of the effect of field stimulation with different lead placements.
      A trial of a deep peripheral fascial lead for sacral and coccygeal field
      stimulation is a simple option and may be a reasonable approach to consider in
      the range of treatments for chronic coccygeal pain.

PMID- 29333356
TI  - Metachronous Testicular Cancer After Orchiectomy: A Rare Case.
AB  - Testicular cancer represents approximately 1% of all cancers diagnosed in males.
      The prevalence of bilateral testicular germ cell tumor cases varies from 1% to
      5%. Intratubular germ cell neoplasia (ITGCN) is a precursor for almost all
      testicular germ cell tumors (TGCT) and is one of the highest risks of developing
      contralateral testicular cancer. The radical orchiectomy is still preferred for
      the treatment of testicular cancer. However, in some cases like solitary testis,
      bilateral cancer or if the tumor size is under 30% percent of the testicular
      extent, organ-sparing surgery can be an option. There are just a few published
      reports of metachronous contralateral testicular cancer, developed after
      orchiectomy with the histopathology of the intratubular germ cell neoplasia.

PMID- 29333357
TI  - Salvage Stereotactic Radiosurgery for Multiple Brain Recurrences: How Much is
      Enough?
AB  - Stereotactic radiosurgery (SRS) can be used as a salvage treatment in selected
      patients with recurrent brain metastases after previous brain radiation. We
      report the case of a patient with metastatic lung adenocarcinoma who experienced
      recurrence numerous times in the brain and was successfully treated each time
      with SRS. For this patient, brain imaging surveillance helped identify metastases
      early for salvage SRS. We have also included a discussion of published literature
      regarding the neurocognitive toxicity of repeated courses of SRS.

PMID- 29333358
TI  - Investigating the Seasonal and Diurnal Cycles of Ocean Vector Winds Near the
      Philippines Using RapidScat and CCMP.
AB  - The seasonal and diurnal cycles of ocean vector winds in the domain of the South
      China Sea are characterized and compared using RapidScat and the Cross-Calibrated
      Multi-Platform (CCMP) data sets. Broad agreement in seasonal flow patterns exists
      between these data sets during the year 2015. Both observe the dramatic reversal
      from wintertime trade winds (November-April) to westerly flow associated with the
      summer monsoon (May-October). These seasonal changes have strong but not
      equivalent effects on mean wind divergence patterns in both data sets.
      Specifically near the Philippines, the data sets agree on several aspects of the
      seasonal mean and diurnal cycle of near-surface vector winds and divergence. In
      particular, RapidScat and CCMP agree that daytime onshore and nocturnal offshore
      flow patterns affect the diurnal cycle of winds up to ~200 km west of Luzon,
      Philippines. Observed disagreements over the diurnal cycle are explainable by
      measurement uncertainty, as well as shortcomings in both data sets.

PMID- 29333359
TI  - Activities of daily living independence level for home discharge in stroke
      patients based on number of caregivers: an analysis of the Japan Rehabilitation
      Database.
AB  - Purpose This study aimed to calculate cut-off values of activities of daily
      living independence level for stroke patient home discharge based on the number
      of family caregivers. Method The subjects comprised 1442 stroke patients (26
      hospitals) who were registered of the Japanese Rehabilitation Database. Receiver
      operating characteristic curves were used to elucidate the BI and FIMR instrument
      scores necessary for home discharge. Analysis was performed for each subject
      according to the number of family caregivers, i.e., no caregiver, one person, two
      persons or more, and overall. Result The BI cut-off points that discriminated
      between home discharge and other were 65/60 points overall, 75/70 points in
      patients with no caregiver, 65/60 points in patients with one caregiver, and
      60/55 points in patients with two or more caregivers. The FIMR instrument cut-off
      points were 90/89 points overall, 101/100 points in patients with no caregiver,
      87/86 points in patients with one caregiver, and 87/86 points in patients with
      two or more caregivers. Conclusion Our results indicated that home discharge for
      patients with many caregivers was possible even with low ADL independence levels,
      and that there was a large difference in cut-off values depending on the presence
      or absence of one caregiver.

PMID- 29333360
TI  - Correlation between changes of contralesional cortical activity and motor
      function recovery in patients with hemiparetic stroke.
AB  - OBJECTIVE: To investigate the correlation between changes of contralesional
      cortical excitability evaluated by transcranial magnetic stimulation (TMS) and
      functional recovery in patients with hemiparetic stroke. METHODS: Eight
      inpatients (mean age: 75.9+/-13.8 years) with mild to moderate hemiparesis were
      enrolled. TMS was delivered to the optimal scalp position over the contralesional
      (ipsilateral to the paresis) primary motor cortex (M1) to activate the unaffected
      flexor carpi radialis muscle (FCR) while the patient picked up a wooden block
      with the affected hand. The amplitude of the motor-evoked potential (MEP) was
      measured and then was divided by the resting MEP amplitude (MEP ratio). For
      evaluation of motor function, we tested grip strength (GS), performed the upper
      extremity motor section of the Fugl-Meyer Assessment (FMA-UE), and performed the
      Purdue Pegboard Test (PPT) when the patients were admitted to our hospital (T1)
      and 2 months after admission (T2). RESULTS: The MEP ratio was significantly
      decreased at the second examination. The partial correlations between the MEP
      ratio and FMA-UE at T1, and PPT of an affected hand at T2 were observed while
      controlling for the period after stroke onset as the confounding variable.
      CONCLUSION: The reduction of contralesional cortical hyperactivity is related to
      the functional recovery in part, but not related with the period after stroke
      onset. This suggests that enhanced reduction of contralesional M1 hyperactivity
      contributes to functional recovery after stroke.

PMID- 29333361
TI  - Factors affecting health-related quality of life one year after lumbar spinal
      fusion.
AB  - OBJECTIVE: To identify preoperative factors that affect the medical outcome study
      36-item short form health survey (SF-36) score 1 year after lumbar spinal fusion.
      METHODS: Participants were selected from among 624 patients who underwent lumbar
      spinal fusion between April 1, 2009 and March 31, 2011 who were followed up for 1
      year or more. The SF-36 version 2 was used to evaluate HRQOL. The following
      preoperative parameters were investigated: sex, age, body mass index (BMI),
      employment status (other than home-making), living with other family members,
      smoking, orthopedic disorder in another part of the body (other than lumbar
      spinal disease), history of lumbar spinal surgery, bladder function, and leg
      muscle strength. RESULTS: 94 patients were included. None of the independent
      preoperative factors exhibited a high degree of correlation, and the absence of
      multicollinearity was confirmed before further analysis was performed. The first
      canonical variates were age and leg muscle strength, which had a major effect on
      physical functioning, role physical, and role emotional 1 year after surgery, and
      the second canonical variates were employment status, sex, and orthopedic
      disorder in another part of the body, which had a major effect on general health
      1 year after surgery. CONCLUSIONS: The SF-36 score 1 year after lumbar spinal
      fusion was affected by the preoperative factors of age, leg muscle strength,
      living with other family members, employment status, sex, and orthopedic
      disorders in another part of the body.

PMID- 29333362
TI  - The coordination of joint movements during sit-to-stand motion in old adults: the
      uncontrolled manifold analysis.
AB  - OBJECTIVE: Sit-to-stand motion (STS) is a dynamic motion utilized in fundamental
      activities of daily living and requires extensive joint movement in the lower
      extremities and the trunk and coordination of multiple body segments. The present
      study aimed to investigate whether aging affects the motor coordination of joint
      movements required to stabilize the horizontal and vertical movement of center of
      mass using the uncontrolled manifold (UCM) analysis. METHOD: We recruited 39
      older adults with no musculoskeletal and/or neuromuscular conditions that
      affected STS, along with 21 healthy younger adults. All subjects performed five
      STS trials from a chair with the seat height adjusted to the length of their
      lower leg at a self-selected motion speed. Kinematic data were collected using a
      three-dimensional motion analysis system. We performed the UCM analysis to assess
      the effects of joint angle variance (elemental variable) to stabilize the
      horizontal and vertical movement of COM (performance variable) and calculated the
      joint angle variance that does not affect COM (VUCM), the variance that affects
      COM (VORT), and the synergy index (DeltaV). RESULTS: DeltaV values in the
      horizontal direction were higher in the older adults than in the younger adults,
      but DeltaV values in the vertical direction were lower in the older adults than
      in the younger adults. CONCLUSION: Older adults require increasing levels of
      stabilization of horizontal movement of COM after buttocks-off in the STS
      maneuver. As a result, variance in the joint angle of the lower extremities
      indicated no kinematic synergy for stabilizing the vertical movement of COM.

PMID- 29333364
TI  - Biodegradable osteofixation in bimaxillary orthognathic surgery.

PMID- 29333363
TI  - Creating a multi-center rare disease consortium - the Consortium of Eosinophilic
      Gastrointestinal Disease Researchers (CEGIR).
AB  - Eosinophilic gastrointestinal disorders (EGIDs) affect various segments of the
      gastrointestinal tract. Since these disorders are rare, collaboration is
      essential to enroll subjects in clinical studies and study the broader
      population. The Rare Diseases Clinical Research Network (RDCRN), a program of the
      National Center for Advancing Translational Sciences (NCATS), funded the
      Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR) in 2014
      to advance the field of EGIDs. CEGIR facilitates collaboration among various
      centers, subspecialties, patients, professional organizations and patient
      advocacy groups and includes 14 clinical sites. It has successfully initiated two
      large multi-center clinical studies looking to refine EGID diagnoses and
      management. Several pilot studies are underway that focus on various aspects of
      EGIDs including novel therapeutic interventions, diagnostic and monitoring
      methods, and the role of the microbiome in pathogenesis. CEGIR currently nurtures
      five physician-scholars through a career training development program and has
      published more than 40 manuscripts since its inception. This review focuses on
      CEGIR's operating model and progress and how it facilitates a framework for
      exchange of ideas and stimulates research and innovation. This consortium
      provides a model for progress on other potential clinical areas.

PMID- 29333365
TI  - Association between headache and temporomandibular disorder.
AB  - Headaches are one of the most common conditions associated with temporomandibular
      disorder (TMD). In the present paper, we evaluated the relationship between
      headache and TMD, determined whether headache influences the symptoms of TMD, and
      reported two cases of TMD accompanied by headache. Our practical experience and a
      review of the literature suggested that headache increases the frequency and
      intensity of pain parameters, thus complicating dysfunctional diseases in both
      diagnostic and treatment phases. Therefore, early and multidisciplinary treatment
      of TMD is necessary to avoid the overlap of painful events that could result in
      pain chronicity.

PMID- 29333366
TI  - A review of temporomandibular joint-related papers published between 2014-2015.
AB  - We conducted a retrospective study and reviewed the temporomandibular joint (TMJ)
      related papers published in a leading international journal, Journal of Oral and
      Maxillofacial Surgery, between January 2014 and December 2015. The study was
      conducted to ascertain and compare the trends of articles being published in the
      years 2014 and 2015. A total of 28 articles were reviewed, of which most of the
      full-length articles were on clinical management and outcomes and the role of
      radiology. The bulk of the studies were prospective, and less interest was shown
      in experimental research. A thorough review and analysis thus gives the
      impression that there is a great need for well-designed clinical studies on TMJ.

PMID- 29333367
TI  - Stepwise verification of bone regeneration using recombinant human bone
      morphogenetic protein-2 in rat fibula model.
AB  - Objectives: The purpose of this study was to introduce our three experiments on
      bone morphogenetic protein (BMP) and its carriers performed using the critical
      sized segmental defect (CSD) model in rat fibula and to investigate development
      of animal models and carriers for more effective bone regeneration. Materials and
      Methods: For the experiments, 14, 16, and 24 rats with CSDs on both fibulae were
      used in Experiments 1, 2, and 3, respectively. BMP-2 with absorbable collagen
      sponge (ACS) (Experiments 1 and 2), autoclaved autogenous bone (AAB) and fibrin
      glue (FG) (Experiment 3), and xenogenic bone (Experiment 2) were used in the
      experimental groups. Radiographic and histomorphological evaluations were
      performed during the follow-up period of each experiment. Results: Significant
      new bone formation was commonly observed in all experimental groups using BMP-2
      compared to control and xenograft (porcine bone) groups. Although there was some
      difference based on BMP carrier, regenerated bone volume was typically reduced by
      remodeling after initially forming excessive bone. Conclusion: BMP-2 demonstrates
      excellent ability for bone regeneration because of its osteoinductivity, but
      efficacy can be significantly different depending on its delivery system. ACS and
      FG showed relatively good bone regeneration capacity, satisfying the essential
      conditions of localization and release-control when used as BMP carriers. AAB
      could not provide release-control as a BMP carrier, but its space-maintenance
      role was remarkable. Carriers and scaffolds that can provide sufficient support
      to the BMP/carrier complex are necessary for large bone defects, and AAB is
      thought to be able to act as an effective scaffold. The CSD model of rat fibula
      is simple and useful for initial estimate of bone regeneration by agents
      including BMPs.

PMID- 29333368
TI  - Oral lesions associated with human immunodeficiency virus in 75 adult patients: a
      clinical study.
AB  - Objectives: The objective of this study was to investigate the presence of oral
      lesions in human immunodeficiency virus/acquired immunodeficiency syndrome
      (HIV/AIDS) patients in a descriptive cross-sectional study, and to establish
      their presence according to levels of CD4+ cells (including the CD4+/CD8+ cell
      ratio). Materials and Methods: A total of 75 patients infected with HIV were
      included. Oral lesions were observed and classified using World Health
      Organization classification guidelines. Potential correlations between the
      presence and severity of oral lesions and CD4+ cells, including the CD4+/CD8+
      cell ratio, were studied. Results: The most frequent oral lesion detected was
      oral pseudomembranous candidiasis (80.0%), followed by periodontal disease
      (40.0%), herpetic lesions (16.0%), hairy leukoplakia (16.0%), gingivitis (20.0%),
      oral ulceration (12.0%), Kaposi's sarcoma (8.0%), and non-Hodgkin's lymphoma
      (4.0%). The CD4+ count was <200 cells/mm3 in 45 cases (60.0%), between 200-500
      cells/mm3 in 18 cases (24.0%), and >500 cells/mm3 in 12 cases (16.0%). The mean
      CD4+ count was 182.18 cells/mm3. The mean ratio of CD4+/CD8+ cells was 0.26. All
      patients showed at least one oral manifestation. Conclusion: There was no
      correlation between the CD4+/CD8+ cell ratio and the presence of oral lesions.
      The severity of the lesions was more pronounced when the CD4+ cell count was less
      than 200 cells/mm3.

PMID- 29333369
TI  - Assessment of the anterior loop of the inferior alveolar nerve via cone-beam
      computed tomography.
AB  - Objectives: The aim of this study was to evaluate different anatomical variants
      of the anterior loop of the inferior alveolar nerve (IAN) via cone-beam computed
      tomography (CBCT). Materials and Methods: CBCT images of 71 patients (36 males
      and 35 females) were evaluated. We used the classification described by Solar for
      IAN evaluation. In this classification, three different types of IAN loops were
      introduced prior to emerging from the mental foramen. We classified patients
      according to this system and introduced a new, fourth type. Results: Type I was
      seen in 15 sites (10.6%), type II in 39 sites (27.5%), and type III in 50 sites
      (35.2%). We found a new type in 38 sites (26.8%) that constituted a fourth type.
      Conclusion: We found that type III was the most common variant. In the fourth
      type, the IAN was not detectable because the main nerve was adjacent to the
      cortical plate and the incisive branch was thinner than the main branch and
      alongside it. In this type, more care is needed for surgeries including inferior
      alveolar and mental nerve transposition.

PMID- 29333370
TI  - The efficacy of oral habit modification on headache.
AB  - Objectives: Headache is the most common complaint of patients suffering from
      temporomandibular joint disorders (TMDs). Thus, temporomandibular joint (TMJ)
      examinations maybe necessary in patients with headache. Considering the high
      prevalence of bruxism and TMDs in patients with headache the effects of
      conservative TMD treatment on headache should be assessed. Materials and Methods:
      Patients were questioned about headaches in the past three months. Those
      responding affirmatively to this question were examined for TMD and bruxism.
      After the examinations, 219 patients remained in the study and received self
      management instructions. Patients were requested to modify oral habits except
      when eating or sleeping. The degree of pain (visual analogue scale), headache
      disability index (HDI), frequency of headaches (FH) per month and TMD intensity
      were evaluated. Results: The median levels of pain, HDI, FH, and TMD intensity
      were 8, 44, 8, and 7, respectively, before modifying oral habits and decreased to
      4, 24, 2, and 3, respectively, after intervention. These decreases were
      statistically significant. Conclusion: Having patients maintain free space
      between the teeth and relax muscles can be an efficient method to treat headache
      and TMD, especially when repeated frequently.

PMID- 29333371
TI  - Use of repeat anterior maxillary distraction to correct residual midface
      hypoplasia in cleft patients.
AB  - Objectives: The study was designed to evaluate the efficacy of performing a
      second, repeat anterior maxillary distraction (AMD) to treat residual cleft
      maxillary hypoplasia. Materials and Methods: Five patients between the ages of 12
      to 15 years with a history of AMD and with residual cleft maxillary hypoplasia
      were included in the study. Inclusion was irrespective of gender, type of cleft
      lip and palate, and the amount of advancement needed. Repeat AMD was executed in
      these patients 4 to 5 years after the primary AMD procedure to correct the cleft
      maxillary hypoplasia that had developed since the initial procedure.
      Orthopantomogram (OPG) and lateral cephalograms were taken for evaluation
      preoperatively, immediately after distraction, after consolidation, and one year
      postoperatively. The data obtained was tabulated and a Mann Whitney U-test was
      used for statistical comparisons. Results: At the time of presentation, a
      residual maxillary hypoplasia was observed with a well maintained distraction gap
      on the OPG which ruled out the occurrence of a relapse. Favorable movement of the
      segments without any resistance was seen in all patients. Mean maxillary
      advancement of 10.56 mm was achieved at repeat AMD. Statistically significant
      increases in midfacial length, SNA angle, and nasion perpendicular to point A
      distance was achieved (P=0.012, P=0.011, and P=0.012, respectively). Good profile
      was achieved for all patients. Minimal transient complications, for example
      anterior open bite and bleeding episodes, were managed. Conclusion: Addressing
      the problem of cleft maxillary hypoplasia at an early age (12-15 years) is
      beneficial for the child. Residual hypoplasia may develop in some patients, which
      may require additional corrective procedures. The results of our study show that
      AMD can be repeated when residual deformity develops with the previous procedure
      having no negative impact on the results of the repeat procedure.

PMID- 29333372
TI  - Ghost cell odontogenic carcinoma on right mandible and its respective surgical
      reconstruction: a case report.
AB  - Calcifying cystic odontogenic tumor (CCOT) is defined as an odontogenic cyst-like
      benign neoplasm that characteristically contains several ghost cells,
      ameloblastoma-like epithelium, and occasional calcification. Ghost cell
      odontogenic carcinoma (GCOC), a malignant form of CCOT, is an exceptionally rare
      malignant tumor. In this report, we present a case of a 53-year-old man whose
      chief complaint was a solitary mass on the right mandible area. The mass was
      completely removed through an extraoral surgical approach and reconstructive
      surgery was performed in two phases.

PMID- 29333373
TI  - Correction of congenital cleft earlobe with front and back flaps.
AB  - Congenital auricular deformities may be either deformational or malformational.
      Malformational anomalies present with a skin or cartilage shortage. Two cases
      with congenital cleft earlobe were presented. A new surgical technique using a
      two-layered repair with front and back flaps were introduced. She waited to begin
      wearing earrings until six months after the surgery to prevent possible scar
      contracture. The patients were followed up for a period ranging from 3 to 14
      months. The earlobe volume deficiency was replaced, and acceptable scar
      maturation was obtained.

PMID- 29333374
TI  - Asymptomatic bilateral maxillary and mandibular impacted permanent canines:
      serendipity in dental outpatient department.

PMID- 29333375
TI  - Impact of FTO SNPs rs9930506 and rs9939609 in Prostate Cancer Severity in a
      Cohort of Puerto Rican Men.
AB  - Background: Obesity is prevalent in PR and has been associated with prostate
      cancer (PCa) mortality and aggressiveness. Polymorphisms (SNPs) rs9930506 and
      rs9939609 in the FTO gene have been associated with both obesity and PCa. The aim
      of this work was to ascertain whether the presence of these SNPs is associated
      with PCa risk and severity in a cohort of Puerto Rican men. Methods and findings:
      The study population consisted of 513 Puerto Rican men age ranging from 40-79
      years old who underwent radical prostatectomy (RP) as the first treatment for PCa
      and 128 healthy Puerto Rican men age ranging from 40-79 years old. Genomic DNA
      (gDNA) was extracted and SNPs were determined by Real-Time PCR. PCa severity was
      defined based on RP stage and Gleason Score. The relationship of FTO SNPs with
      demographic, clinical characteristics, PCa status and PCa severity were assessed.
      Logistic regression models with a 95% confidence interval (CI) determined SNPs
      interaction with PCa risk and severity odds ratio (ORs). Results and discussion:
      BMI, age and PSA were considered as confounders. Hardy-Weinberg equilibrium was
      present for both SNPs. The heterozygous forms (A/G; T/A) were the most prevalent
      genotypes and the frequency of alleles and genotypes for both SNPs agreed with
      those published in 1000 genomes. Results suggest an inverse association between
      the mutated rs9939609 and the risk of having PCa (OR: 0.53, 95% CI: 0.31-0.92)
      and a positive association with overweight (OR: 1.05, 95% CI: 0.68-1.62).
      Importantly, among the cases that were overweight, those with mutated rs9939609
      had a greater chance of high severity PCa (OR: 1.39, 95% CI: 0.84-2.32) although
      these results were not statistical significant upon adjustment. Limitations of
      the study were the relatively small cohort and lack of access to the weight
      history of all our subjects. Conclusion: Results offer a research line to be
      followed with an expanded number of subjects that may provide a better
      statistical significance, to unravel the high mortality rate in this population.

PMID- 29333377
TI  - Dietary L-Arginine Intakes and the Risk of Metabolic Syndrome: A 6-Year Follow-Up
      in Tehran Lipid and Glucose Study.
AB  - This study was conducted to investigate whether regular dietary intake of L
      arginine could affect the occurrence of metabolic syndrome (MetS). Eligible adult
      men and women (n=1,237), who participated in the Tehran Lipid and Glucose Study,
      were followed for a median of 6.3 years. Dietary intakes of L-arginine and serum
      nitrate and nitrite (NOx) concentration were assessed at baseline (2006~2008),
      and demographics, anthropometrics, and biochemical variables were evaluated at
      baseline and follow-up examinations. The occurrence of MetS was assessed in
      relation to total L-arginine, intakes of L-arginine from animal and plant
      sources, with adjustment of potential confounding variables. Participants who had
      higher intake of L-arginine also had higher serum NOx at baseline (35.0 vs. 30.5
      MUmol/L, P<0.05). After 6 years of follow-up, higher intakes of L-arginine from
      animal sources were accompanied with increased risk of MetS [odd ratios
      (OR)=1.49, 95% confidence interval (95% CI)=1.02~2.18]. Compared to the lowest,
      the highest intakes of L-arginine from plant sources were related to
      significantly reduced risk of MetS (OR=0.58, 95% CI=0.32~0.99). In conclusion,
      our findings suggest a potentially protective effect of plant derived L-arginine
      intakes against development of MetS and its phenotypes; moreover, higher intakes
      of L-arginine from animal sources could be a dietary risk factor for development
      of metabolic disorders.

PMID- 29333378
TI  - Associations between Self-Reported Sleep Quality and Duration and Dietary
      Consumptions, Psychological Symptoms, and Obesity in Korean Adults.
AB  - Sleep pattern disruptions have been reported to be associated with an increased
      risk of obesity. This study was performed to investigate the association between
      sleep quality and sleep duration with dietary consumption, psychological factors,
      and obesity in Korean adults. A total of 288 Korean men and women who visited a
      public health center were included in this study. Data on general
      characteristics, health-related habits, psychological symptoms, dietary intake,
      and sleep patterns (including quality and duration) were collected using self
      report questionnaires. Approximately half of the included Korean adults
      experienced sleep of low quality and short duration. Subjects who reported short
      sleep durations had a significantly higher weight (P=0.015), body mass index
      (P<0.001), and prevalence of obesity (P=0.012) than those reporting proper sleep
      durations. After adjustment for covariates, subjects reporting short sleep
      durations consumed more dietary carbohydrates (P=0.043) and higher levels of
      perceived stress (P=0.001), depression (P=0.001), and anxiety (P<0.001) than
      subjects reporting proper sleep durations. However, obesity-related variables,
      dietary intake and psychosocial symptoms did not differ significantly by reported
      sleep quality. The results of this study demonstrated that sleep duration but not
      sleep quality was associated with dietary macronutrient intake and psychological
      symptoms, which might affect obesity.

PMID- 29333376
TI  - Anti-Inflammatory and Anti-Obesity Properties of Food Bioactive Components:
      Effects on Adipose Tissue.
AB  - Obesity is an epidemic and costly disease affecting 13% of the adult population
      worldwide. Obesity is associated with adipose tissue hypertrophy and hyperplasia,
      as well as pathologic endocrine alterations of adipose tissue including local and
      chronic systemic low-grade inflammation. Moreover, this inflammation is a risk
      factor for both metabolic syndrome (MetS) and insulin resistance. Basic and
      clinical studies demonstrate that foods containing bioactive compounds are
      capable of preventing both obesity and adipose tissue inflammation, improving
      obesity-associated MetS in human subjects and animal models of obesity. In this
      review, we discuss the anti-obesity and anti-inflammatory protective effects of
      some bioactive polyphenols of plant origin and omega-3 polyunsaturated fatty
      acids, available for the customers worldwide from commonly used foods and/or as
      components of commercial food supplements. We review how these bioactive
      compounds modulate cell signaling including through the nuclear factor-kappaB,
      adenosine monophosphate-activated protein kinase, mitogen-activated protein
      kinase, toll-like receptors, and G-protein coupled receptor 120 intracellular
      signaling pathways and improve the balance of pro- and anti-inflammatory
      mediators secreted by adipose tissue and subsequently lower systemic inflammation
      and risk for metabolic diseases.

PMID- 29333379
TI  - Broccoli (Brassica oleracea) Reduces Oxidative Damage to Pancreatic Tissue and
      Combats Hyperglycaemia in Diabetic Rats.
AB  - Oxidative stress plays a pivotal role in the development of diabetes and
      hyperglycaemia. The protective effects of natural extracts against diabetes are
      mainly dependent on their antioxidant and hypoglycaemic properties. Broccoli
      (Brassica oleracea) exerts beneficial health effects in several diseases
      including diabetes; however, the mechanism has not been elucidated yet. The
      present study was carried out to evaluate the potential hypoglycaemic and
      antioxidant properties of aqueous broccoli extracts (BEs) in diabetic rats.
      Streptozotocin (STZ) drug was used as a diabetogenic agent in a single
      intraperitoneal injection dose of 50 mg/kg body weight. The blood glucose level
      for each rat was measured twice a week. After 8 weeks, all animals were fasted
      overnight and sacrificed; pancreatic tissues were homogenized and used for
      measuring oxidative DNA damage, biochemical assessment of glutathione (GSH), and
      total antioxidant capacity (TAC) as well as histopathological examination for
      pancreatic tissues was examined. Diabetic rats showed significantly higher levels
      of DNA damage, GSH depletion, and impaired TAC levels in comparison to non
      diabetics (P<0.05). The treatment of diabetic rats with BE significantly reduced
      DNA damage and conserved GSH and TAC values (P<0.01). BE attenuated pancreatic
      histopathological changes in diabetic rats. The results of this study indicated
      that BE reduced the STZ mediated hyperglycaemia and the STZ-induced oxidative
      injury to pancreas tissue. The used in vivo model confirmed the efficacy of BE as
      an anti-diabetic herbal medicine and provided insights into the capacity of BE to
      be used for phytoremediation purposes for human type 2 diabetes.

PMID- 29333380
TI  - Anti-Obesity Property of Lichen Thamnolia vermicularis Extract in 3T3-L1 Cells
      and Diet-Induced Obese Mice.
AB  - Thamnolia vermicularis (TV) is an edible lichen that is prevalent in the alpine
      zone of East Asia. This study evaluated the feasibility of using TV acetone
      extracts as a functional food based on experiments using cell line and obese
      mice. The cellular triglyceride levels and Oil red O staining of 3T3-L1 cells
      indicated that TV extracts (5 and 10 MUg/mL) dose-dependently suppressed
      adipocyte differentiation and lipid accumulation compared with the control. The
      TV extract (0.4%, w/w) in a high-fat diet (HFD) was supplemented to C57BL/6N mice
      for 12 weeks, and TV extract supplement significantly reduced visceral fat mass
      and body weight compared with HFD feeding alone. The TV extract also induced
      significant decreases in serum and hepatic lipids, whereas it increased the serum
      high-density lipoproteins-cholesterol/total cholesterol ratio and fecal lipids
      levels. Moreover, the TV extract led to significantly lower homeostasis model
      assessment of insulin resistance in diet-induced obese mice. Taken together,
      these results suggest that the TV extract may have anti-obesity effects,
      including lipid-lowering, and it is a natural resource with the potential for use
      in obesity management.

PMID- 29333381
TI  - Changes in Drosophila melanogaster Sleep-Wake Behavior Due to Lotus (Nelumbo
      nucifera) Seed and Hwang Jeong (Polygonatum sibiricum) Extracts.
AB  - We evaluated the sleep enhancement activity of the medicinal herbs valerian
      (Valeriana officinalis), jujube (Ziziphus jujube), lotus seed (Nelumbo nucifera),
      Gastrodia elata, Polygonatum sibiricum, and baekbokryung (Poria cocos), which can
      relieve insomnia in a Drosophila model. Locomotor activity was measured in the
      Drosophila model to evaluate the sleep activity of Korean medicinal herbs
      traditionally used as sleep aids. The group treated with lotus seed extract
      showed less nocturnal activity. Treatment with 10 or 20 mg/mL of P. sibiricum
      significantly reduced nocturnal activity compared to the control group (P<0.05).
      The activity and sleep bouts of fruit flies were significantly decreased by a
      high-dose treatment (10 mg/mL) of lotus or P. sibiricum extracts at night.
      Caffeine-treated Drosophila showed increased nocturnal activity and decreased
      total sleep time (P<0.05). Flies receiving the 10 mg-doses of lotus seed or P.
      sibiricum extract showed significantly different nocturnal locomotor activity and
      total sleep time compared to caffeine-treated Drosophila. Lotus seed and P.
      sibiricum extracts are attractive and valuable sleep-potentiating nutraceuticals.

PMID- 29333382
TI  - Antioxidant and Quinone Reductase Activity of Soyasaponins in Hepa1c1c7 Mouse
      Hepatocarcinoma Cells.
AB  - Saponins have been reported to possess several health beneficial activities
      including hypocholesterolemic, immune-stimulatory, and anticarcinogenic. The
      objectives of this study were to determine if soysaponins are radical scavengers
      and inducers of quinone reductase (QR) activity in Hepa1c1c7 murine hepatoma cell
      line. The antioxidant capacity of soyasaponin was evaluated using the 1,1'
      diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzthiazoline-6
      sulfonic acid) (ABTS) radical scavenging methods. Soyasaponin showed 75.7%
      radical scavenging activity in the DPPH assay and 81.4% in the ABTS method at 100
      MUg/mL concentration. Cellular proliferation was determined using the
      methylthiazolyldiphenyl-tetrazolium bromide colorimetric assay. Soyasaponin
      inhibited cell growth in a dose-dependent (0.1~100 MUg/mL) manner, and growth
      inhibition was 30% and 39% at 100 MUg/mL of saponin after 24 h and 48 h
      incubation, respectively. Soyasaponin showed QR induction in a dose-dependent
      manner. Ten, 50, and 100 MUg/mL of soyasaponin resulted in a 1.6-, 2.2-, and 2.9
      fold induction of QR, respectively. These results provide a basis for the
      potential of soysaponin as a chemopreventive agent.

PMID- 29333383
TI  - Inhibitory Effects of Butein on Adipogenesis through Upregulation of the Nrf2/HO
      1 Pathway in 3T3-L1 Adipocytes.
AB  - Butein is reported to have many biological effects, including anti-fibrogenic,
      anti-cancer, and anti-inflammatory activities. This study investigated the
      effects of butein on adipocyte differentiation and the Nrf2/heme oxygenase-1 (HO
      1) pathway's involvement in its anti adipogenic mechanism. Butein treatment
      reduced protein expression of key adipogenic transcription factors such as CCAAT
      enhancer-binding protein alpha (C/EBPalpha) and peroxisome proliferator-activated
      receptor gamma (PPARgamma). At a concentration of 5, 10, and 25 MUM butein,
      PPARgamma was decreased by 78.8, 68.3, and 31.4% and C/EBPalpha by 87.3, 71.7,
      and 42.1%, respectively. Butein also increased Nrf2 and HO-1 protein expression
      in a dose-dependent manner. Treatment with zinc protoporphyrin, a specific HO-1
      inhibitor, abolished the inhibitory effects of butein on adipogenic transcription
      factor protein expression. Therefore, butein inhibits adipogenesis, at least
      partially, through upregulation of the Nrf-2/HO-1 signaling pathway in 3T3-L1
      adipocytes.

PMID- 29333384
TI  - Antioxidant and Cytoprotective Activities of Enzymatic Extracts from Rhizoid of
      Laminaria japonica.
AB  - Rhizoid of Laminaria japonica was hydrolyzed with proteases and carbohydrases to
      obtain antioxidant materials. Oxygen radical absorbance capacity (ORAC) of the
      enzymatic extracts was evaluated and the Protamex extract (PE) exhibited the
      highest ORAC value. PE also potently scavenged 2,2-diphenyl-1-picrylhydrazyl
      radical, 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic) acid cation radical,
      and hydrogen peroxide (H2O2) and had good reducing power. PE inhibited hydroxyl
      radical-induced DNA scission by measuring the conversion of supercoiled pBR322
      plasmid DNA to the open circular form. The cytoprotective effect of PE against
      H2O2-induced hepatic cell damage was also investigated. PE showed a dose
      dependent cytoprotective effect in cultured hepatocytes by inhibiting
      intracellular reactive oxygen species scavenging activity. In addition, PE up
      regulated the expression of heme oxygenase-1, which is a cytoprotective enzyme,
      by activating translocation of nuclear factor-erythroid 2-related factor 2. Taken
      together, the enzymatic extract of rhizoid of L. japonica, particularly PE, may
      be useful for antioxidant additives.

PMID- 29333385
TI  - Kaempferol Inhibits Angiogenesis by Suppressing HIF-1alpha and VEGFR2 Activation
      via ERK/p38 MAPK and PI3K/Akt/mTOR Signaling Pathways in Endothelial Cells.
AB  - Kaempferol has been shown to inhibit vascular formation in endothelial cells.
      However, the underlying mechanisms are not fully understood. In the present
      study, we evaluated whether kaempferol exerts antiangiogenic effects by targeting
      extracellular signal-regulated kinase (ERK)/p38 mitogen-activated protein kinase
      (MAPK) and phosphoinositide 3-kinase (PI3K)/Akt/mechanistic target of rapamycin
      (mTOR) signaling pathways in endothelial cells. Endothelial cells were treated
      with various concentrations of kaempferol for 24 h. Cell viability was determined
      by the 3- (4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay;
      vascular formation was analyzed by tube formation, wound healing, and mouse
      aortic ring assays. Activation of hypoxia-inducible factor-1alpha (HIF-1alpha),
      vascular endothelial growth factor receptor 2 (VEGFR2), ERK/p38 MAPK, and
      PI3K/Akt/mTOR was analyzed by Western blotting. Kaempferol significantly
      inhibited cell migration and tube formation in endothelial cells, and suppressed
      microvessel sprouting in the mouse aortic ring assay. Moreover, kaempferol
      suppressed the activation of HIF-1alpha, VEGFR2, and other markers of ERK/p38
      MAPK and PI3K/Akt/mTOR signaling pathways in endothelial cells. These results
      suggest that kaempferol inhibits angiogenesis by suppressing HIF-1alpha and
      VEGFR2 activation via ERK/p38 MAPK and PI3K/Akt/mTOR signaling in endothelial
      cells.

PMID- 29333386
TI  - Antioxidant and Anti-Adipogenic Activities of Trapa japonica Shell Extract
      Cultivated in Korea.
AB  - Trapa japonica shell contains phenolic compounds such as tannins. Studies
      regarding the antioxidant and anti-adipogenic effects of Trapa japonica shell
      cultivated in Korea are still unclear. Antioxidant and anti-adipogenic activities
      were measured by in vitro assays such as 2,2-diphenyl-1-picrylhydrazy (DPPH)
      radical scavenging activity, 2,2'-azinobis( 3-ethylbenzothiazoline-6-sulphonic
      acid) (ABTS) radical scavenging activity, ferric reducing ability of plasma
      assay, reducing power, superoxide dismutase-like activity, and iron chelating
      ability in 3T3-L1 cells. We also measured the total phenol and flavonoids
      contents (TPC and TFC, respectively) in Trapa japonica shell extract. Our results
      show that TPC and TFC of Trapa japonica shell extract were 157.7+/-0.70 mg gallic
      acid equivalents/g and 25.0+/-1.95 mg quercetin equivalents/g, respectively.
      Trapa japonica shell extract showed strong antioxidant activities in a dose
      dependent manner in DPPH and ABTS radical scavenging activities and other
      methods. Especially, the whole antioxidant activity test of Trapa japonica shell
      extract exhibited higher levels than that of butylated hydroxytoluene as a
      positive control. Furthermore, Trapa japonica shell extract inhibited lipid
      accumulation and reactive oxygen species production during the differentiation of
      3T3-L1 preadipocytes. Trapa japonica shell extract possessed a significant
      antioxidant and anti-adipogenic property, which suggests its potential as a
      natural functional food ingredient.

PMID- 29333387
TI  - Physicochemical and Antioxidant Properties of Honeys from the Sundarbans Mangrove
      Forest of Bangladesh.
AB  - This study evaluated the physicochemical, nutritional, antioxidant, and phenolic
      properties of ten honey samples from the Sundarbans mangrove forest, Bangladesh.
      The average pH, electrical conductivity, total dissolved solid, ash, moisture,
      hydroxymethyl furfural, titrable acidity, and absorbance were 4.3, 0.38 mS/cm,
      187.5 ppm, 0.14%, 17.88%, 4.4 mg/kg, 37.7 meq/kg, and 483 mAU, respectively. In
      the honeys, the average contents of Ca, Cu, Fe, K, Mg, Mn, and Na were 95.5,
      0.19, 6.4, 302, 39.9, 3.4, and 597 ppm, respectively, whereas Cd, Cr, Pb, and Ni
      were not found. The average contents of total sugar, protein, lipid, vitamin C,
      polyphenols, flavonoids, and anthocyanins in the honeys were 69.3%, 0.8%, 0.29%,
      107.3 mg/kg, 757.2 mg gallic acid equivalent/kg, 43.1 mg chatechin equivalent/kg,
      and 5.4 mg/kg, respectively. The honeys had strong 1,1-diphenyl-2-picrylhydrazyl
      free radical scavenging activity, reducing power and total antioxidant capacity.
      High-performance liquid chromatography analysis of the honey fractions revealed
      the quantification of six polyphenols namely, (+)-catechin, (-)-epicatechin, p
      caumeric acid, syringic acid, trans-cinnamic acid, and vanillic acid at 194.98,
      330.34, 74.64, 218.97, 49.55, and 118.84 mg/kg, respectively. Therefore, the
      honeys in the Sundarbans are of excellent quality and a prospective source of
      polyphenols, and antioxidants.

PMID- 29333388
TI  - Enhancement of Phenolic Production and Antioxidant Activity from Buckwheat Leaves
      by Subcritical Water Extraction.
AB  - To enhance the production of phenolic compounds with high antioxidant activity
      and reduce the level of phototoxic fagopyrin, buckwheat leaves were extracted
      with subcritical water (SW) at 100~220 degrees C for 10~50 min. The major
      phenolic compounds were quercetin, gallic acid, and protocatechuic acid. The
      cumulative amount of individual phenolic compounds increased with increasing
      extraction temperature from 100 degrees C to 180 degrees C and did not change
      significantly at 200 degrees C and 220 degrees C. The highest yield of individual
      phenolic compounds was 1,632.2 MUg/g dry sample at 180 degrees C, which was 4.7
      fold higher than that (348.4 MUg/g dry sample) at 100 degrees C. Total phenolic
      content and total flavonoid content increased with increasing extraction
      temperature and decreased with increasing extraction time, and peaked at 41.1 mg
      gallic acid equivalents/g and 26.9 mg quercetin equivalents/g at 180 degrees C/10
      min, respectively. 2,2-Diphenyl-1-picrylhydrazyl free radical scavenging activity
      and ferric reducing ability of plasma reached 46.4 mg ascorbic acid equivalents/g
      and 72.3 mmol Fe2+/100 g at 180 degrees C/10 min, respectively. The fagopyrin
      contents were reduced by 92.5~95.7%. Color values L* and b* decreased, and a*
      increased with increasing extraction temperature. SW extraction enhanced the
      yield of phenolic compounds with high antioxidant activity and reduced the
      fagopyrin content from buckwheat leaves.

PMID- 29333389
TI  - Influence of Cooking Methods on Bioactive Compound Content and Antioxidant
      Activity of Brussels Sprouts.
AB  - The effects of different cooking methods on total bioactive compound content were
      determined, and in vitro antioxidant activity in 80% ethanolic extracts of
      Brussels sprouts was evaluated by spectrophotometric methods. Compared to
      uncooked, steamed, and microwaved Brussels sprouts extracted with 80% ethanol
      contained higher amounts of total polyphenols. Uncooked Brussels sprouts
      contained the highest amounts of total flavonoids. Microwaved Brussels sprouts
      contained the highest amounts of total carotenoids (0.35 mg/g) and chlorophylls
      (3.01 mg/g), followed by steamed and uncooked samples. Uncooked fresh Brussels
      sprouts showed the highest antioxidant activity followed by microwaved and
      steamed sprouts. Antioxidant activity was measured with the 2,2-diphenyl-1
      picrylhydrazyl, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), and
      hydroxyl racial scavenging assays as well as the reducing power activity assay,
      and antioxidant activity was found to increase in a concentration-dependent
      manner. Based on these results, cooking or heat treatment may decrease
      antioxidant activities, although their effect on bioactive compound content
      remains controversial.

PMID- 29333390
TI  - Physicochemical and Consumer Acceptance of Tofu Supplemented with Licorice
      Powder.
AB  - To develop functionally and nutritionally improved tofu, the effects of partial
      (0.2~0.8%) replacement with licorice powder (LP) on the quality characteristics
      of tofu were investigated. The pH and turbidity values decreased upon addition of
      increasing amounts of LP (P<0.05). The yield of LP-supplemented tofu was higher
      than that of the control tofu, and it increased as the concentration of LP
      increased (P<0.05). Substituting 0.6% and above of LP significantly hardened the
      texture of tofu (P<0.05) while control and 0.2~0.4% samples were not
      significantly different among them (P> 0.05). Lightness significantly decreased
      with higher LP content in the formulation (P<0.05), as indicated by visual
      observation that the color of tofu became darker. Redness and yellowness
      significantly increased (P<0.05). 2,2-Diphenyl-1-picrylhydrazyl and 2,2'-azino
      bis-3-ethylbenzthiazoline-6-sulphonic acid radical scavenging activities
      significantly increased (P<0.05) with higher substitution of LP, and they were
      well correlated. Tofu incorporated with LP (0.2~0.8%) had a better shelf life
      which was approximately 4.32~26.64 h longer than the control tofu at the elevated
      temperature of 15 degrees C. Finally, consumer acceptance test revealed that
      supplementation of LP more than 0.4% had an adverse effect on general consumer
      acceptance. On the basis of the overall observations, tofu samples supplemented
      with 0.2% (w/w) LP were found to benefit from the functional properties of LP,
      without compromising consumer acceptance.

PMID- 29333391
TI  - Analysis of Antioxidant and Anti-Inflammatory Activities of Solvent Fractions
      from Rhynchosia nulubilis Cultivated with Ganoderma lucidum Mycelium.
AB  - In this study, the crude ethanol Rhynchosia nulubilis cultivated with Ganoderma
      lucidum mycelium (RNGM) extract was solvent fractionated with organic solvents
      such as n-hexane, chloroform, ethyl acetate, and water. The anticancer
      activities, anti-inflammatory activity total polyphenols, total flavonoids,
      isoflavones, and beta-glucan of the solvent fractions of RNGM were studied. The
      ethyl acetate fraction showed the highest 2,2-diphenyl-1-picrylhydrazyl
      scavenging activity of 76.60% at 800 MUg/mL. The ethyl acetate fraction also
      showed higher antioxidant activity in 2,2'-azino-bis(3-ethylbenzothiazoline-6
      sulfonic acid) and ferric reducing ability of plasma assays compared to the other
      fractions. In addition, this study confirmed that the ethyl acetate fraction
      strongly inhibited nitric oxide production. The ethyl acetate fraction had the
      highest amount of total polyphenol and total flavonoid (65.33 mg gallic acid
      equivalent/g and 18.50 mg quercetin equivalent/g, respectively). The ethyl
      acetate fraction (13.02%) showed the highest amount of total beta-glucan,
      followed by the water (6.32%), chloroform (1.43%), and n-hexane fraction (0.85%).
      Therefore, it is suggested that the ethyl acetate fraction of Rhynchosia
      nulubilis cultivated with Ganoderma lucidum mycelium may be potential natural
      sources for nutritional and pharmaceutical applications.

PMID- 29333392
TI  - Enhancing Sensory Perception of Plant Based Nutraceutical Drinks by Combining
      Plants from Different Sources: A Preliminary Study of Tea and Ginger Blend.
AB  - Tea-ginger drink was selected for evaluation due to its nutraceutical potential.
      Panelists rated preference for drinks prepared from tea, ginger, and tea+ginger
      powder for colour, taste, and aroma. The obtained data were evaluated using
      analysis of variance, principal component analysis, and agglomerative
      hierarchical clustering. Also the colour preference scores were evaluated against
      instrumental colour measurements. The ginger drink had lower rating for colour
      preference and the tea drink had lower ratings for aroma and taste preference.
      However, the tea-ginger drink led to enhanced colour, aroma, and taste ratings.
      The colour preference was found to have highest correlation coefficient with the
      hue and chroma of the drinks [r(58)=-0.583, P<0.05 and r(58)=0.566, P<0.05]. This
      study suggests that a sensory quality deficiency in a particular plant based
      drink could be compensated for by blending the drink with another plant based
      drink. This approach could help improve the uptake of plant based nutraceutical
      drinks.

PMID- 29333393
TI  - Effect of Monascus-Fermented Soybean Extracts on Antioxidant and Skin Aging
      Related Enzymes Inhibitory Activities.
AB  - We investigated the in vitro inhibitory activity against skin aging-related
      enzymes and antioxidant activity of Monascus-fermented soybean extracts (MFSEs)
      obtained by using different solvents. The highest Trolox equivalent (TE)
      antioxidant capacity (3.13+/-0.06 mM TE/g) and oxygen radical absorbance capacity
      (2.79+/-0.09 mM TE/g) of MFSEs were evaluated for the methanol and 80% ethanol
      extracts, respectively. The antioxidant capacities increased with increasing
      concentration (0.5~50 mg/mL). In addition, the methanol and 80% ethanol extracts
      showed an effective inhibition against tyrosinase, hyaluronidase, and elastase
      compared with those of acetone and hot water extracts (P<0.05). Results indicate
      that the inhibitory activities against skin aging-related enzymes and antioxidant
      properties provide evidence for the nutricosmetic potentials of Monascus
      fermented soybeans.

PMID- 29333394
TI  - Evaluation of Anti-Wrinkle Effects of DuOligo, Composed of Lactulose and
      Galactooligosaccharides.
AB  - Currently, alternatives to prebiotics for skin treatment are receiving much
      interest. However, little is known about the efficacy of topically applied
      prebiotics in skin anti-aging. This study was conducted to observe the anti-aging
      effects of DuOligo, which is composed of lactulose and galactooligosaccharides
      (GOS). We investigated wrinkle-related parameters by quantitative and qualitative
      skin evaluation in healthy women who consumed DuOligo for 8 weeks. The double
      blind, randomized, and placebo-controlled study included subjects who were
      divided into two groups (Placebo: dextrin 4.5 g/d, n=14, 51.50 y vs. DuOligo:
      DuOligo 4.5 g/d, n=14, 52.65 y). The DuOligo group showed a reduction in mean
      wrinkle length and depth measured via quantitative skin evaluation after 8 weeks,
      whereas the Placebo group showed slight increases in these parameters (P<0.001).
      The wrinkle severity rating scale in the DuOligo group was decreased after 8
      weeks, but it increased in the Placebo group (Placebo group: 0.14 vs. DuOligo
      group: -0.86, P<0.001). The global aesthetic improvement scale for the DuOligo
      group was significantly higher than that for the Placebo group at week 8
      (P<0.001). In conclusion, our findings suggest that oral consumption of DuOligo
      is beneficial to the skin, and present the possibility of new nutritional
      strategies for wrinkle care.

PMID- 29333395
TI  - IL-1B-31 and IL-1Ra polymorphisms associated with increased host susceptibility
      to immune thrompocytopenia.

PMID- 29333396
TI  - Unravelling the genomic landscape of leukemia using NGS techniques: the challenge
      remains.

PMID- 29333397
TI  - Pseudo-Chediak-Higashi inclusions in a case of acute lymphoblastic leukemia.

PMID- 29333398
TI  - Myelodysplastic syndrome with occult diffuse large B-cell lymphoma.

PMID- 29333399
TI  - Sinusoidal infiltration of hepatosplenic lymphoma in liver and bone marrow.

PMID- 29333400
TI  - Brentuximab vedotin: clinical updates and practical guidance.
AB  - Brentuximab vedotin (BV), a potent antibody-drug conjugate, targets the CD30
      antigen. Owing to the remarkable efficacy shown in CD30-positive lymphomas, such
      as Hodgkin's lymphoma and systemic anaplastic large-cell lymphoma, BV was granted
      accelerated approval in 2011 by the US Food and Drug Administration. Thereafter,
      many large-scale trials in various situations have been performed, which led to
      extensions of the original indication. The aim of this review was to describe the
      latest updates on clinical trials of BV and the in-practice guidance for the use
      of BV.

PMID- 29333401
TI  - Management of immune thrombocytopenia: Korean experts recommendation in 2017.
AB  - Management options for patients with immune thrombocytopenia (ITP) have evolved
      substantially over the past decades. The American Society of Hematology published
      a treatment guideline for clinicians referring to the management of ITP in 2011.
      This evidence-based practice guideline for ITP enables the appropriate treatment
      of a larger proportion of patients and the maintenance of normal platelet counts.
      Korean authority operates a unified mandatory national health insurance system.
      Even though we have a uniform standard guideline enforced by insurance
      reimbursement, there are several unsolved issues in real practice in ITP
      treatment. To optimize the management of Korean ITP patients, the Korean Society
      of Hematology Aplastic Anemia Working Party (KSHAAWP) reviewed the consensus and
      the Korean data on the clinical practices of ITP therapy. Here, we report a
      Korean expert recommendation guide for the management of ITP.

PMID- 29333402
TI  - Interleukin-1B (IL-1B-31 and IL-1B-511) and interleukin-1 receptor antagonist (IL
      1Ra) gene polymorphisms in primary immune thrombocytopenia.
AB  - Background: Immune thrombocytopenia (ITP) is an immune-mediated disease caused by
      autoantibodies against platelets membrane glycoproteins GPIIb/IIIa and GPIb/IX.
      The etiology of ITP remains unclear. This study evaluated the association of
      polymorphisms in interleukin (IL)-1B-31, IL-1B-511, and IL-1Ra with ITP. Methods:
      Genotyping of IL-1B-31, IL-1B-511, and IL-1Ra was performed in 118 ITP patients
      and 100 controls by polymerase chain reaction restriction fragment length
      polymorphism and detection of variable number tandem repeats. Results: Genotype
      differences in IL-1B-31 and IL-1Ra were significantly associated with ITP.
      Patients showed a higher frequency of the IL-1B-31 variant allele (T) and a 1.52
      fold greater risk of susceptibility to ITP (odds ratio [OR]=1.52, 95% confidence
      interval [CI]=1.04-2.22, P=0.034). The frequencies of both homozygous and
      heterozygous variant genotypes of IL-1B-31 were higher (OR=2.33, 95% CI=1.069
      5.09, P=0.033 and OR=2.044, 95% CI=1.068-39, P=0.034) among patients and were
      significantly associated with ITP susceptibility. Both homozygous and
      heterozygous variant genotypes of IL-1Ra were also more frequent (OR=4.48, 95%
      CI=1.17-17.05, P=0.0230 and OR=1.80, 95% CI=1.03-3.14, P=0.0494) among patients
      and were associated with ITP risk. IL-1B-31 and IL-1Ra also showed significant
      association with severe ITP. However, IL-1B-511 was not associated with ITP.
      Conclusion: IL-1B-31 and IL-1Ra polymorphisms may significantly impact ITP risk,
      and they could be associated with disease severity, which may contribute to the
      pathogenesis of ITP.

PMID- 29333403
TI  - Treatment outcomes of dose-attenuated CHOP chemotherapy in elderly patients with
      peripheral T cell lymphoma.
AB  - Background: While cyclophosphamide, doxorubicin, vincristine, and prednisolone
      (CHOP) is the most commonly used chemotherapeutic regimen for patients with
      peripheral T-cell lymphomas (PTCLs), elderly patients are more vulnerable to
      associated toxicities. We evaluated the efficacy and safety of dose-attenuated
      CHOP in elderly patients with PTCL. Methods: Patients with PTCL aged >70 years or
      65-70-years with comorbidities were treated with dose-attenuated CHOP
      (cyclophosphamide: 562.5 mg/m2, doxorubicin: 37.5 mg/m2, vincristine: 1.4 mg/m2,
      and prednisolone: 100 mg for five days; 25% reduced dose of cyclophosphamide and
      doxorubicin vs. full-dose CHOP) as first-line therapy were included. Results:
      Forty-four patients (median age, 74 yr) were analyzed. The majority (N=42, 95.5%)
      had advanced stage disease and 36 (81.8%) were classified as high/high
      intermediate risk by the international prognostic index. The overall response
      rate was 61.4%, and 21 patients achieved complete response (47.7%). With median
      follow-up period of 28.8 months, the estimated two-year progression-free and
      overall survival rates were 36.7% and 46.6%, respectively. Grade 3/4 neutropenia
      and thrombocytopenia occurred in 26.9% and 7.4% of 204 total cycles, which
      affected 76.7% and 25.6% of the patients, respectively. Nineteen patients (44.2%)
      experienced febrile neutropenia, and six died due to treatment-related
      toxicities. High lactate dehydrogenase levels and an involvement of >1 extranodal
      sites were prognostic indicators of poor survival. Conclusion: Dose-attenuated
      CHOP does not compromise treatment efficacy but retains significant toxicity. Our
      results suggest that some patients can be effectively treated with dose
      attenuated CHOP, however a novel therapy for elderly patients with PTCL is
      required.

PMID- 29333404
TI  - Relevance of prognostic index with beta2-microglobulin for patients with diffuse
      large B-cell lymphoma in the rituximab era.
AB  - Background: The International Prognostic Index (IPI) has been a useful tool for
      predicting the prognosis of aggressive non-Hodgkin lymphoma in the last 20 years.
      Herein, we aimed to develop a new prognostic model for diffuse large B-cell
      lymphoma (DLBCL) in the rituximab era. Methods: Between March 2004 and June 2012,
      patients with DLBCL treated with rituximab, cyclophosphamide, doxorubicin,
      vincristine, and prednisolone chemotherapy regimen were identified in the
      database of the Asan Medical Center (AMC) Lymphoma Registry. The primary and
      secondary endpoints were a new prognostic index for DLBCL and validation of the
      National Comprehensive Cancer Network-International Prognostic Index in our
      cohort, respectively. Results: The AMC cohort comprised 621 patients. The median
      follow-up duration was 43.3 months (range, 6.2-122.5 mo). Univariate analysis
      revealed that age (<=60 vs. >60 yr), lactate dehydrogenase (LDH; within normal
      vs. increased), Eastern Cooperative Oncology Group performance status (ECOG PS; 0
      or 1 vs. >=2), advanced stage (Ann Arbor stage I/II vs. III/IV), extra-nodal
      involvement (<=1 vs. >1), B symptoms (no vs. yes), and beta-2 microglobulin
      (beta2MG, <=2.5 vs. >2.5) can be used to predict overall survival (OS). In
      multivariate analysis, only age, LDH, ECOG performance status, and beta2MG were
      significantly associated with OS, and we developed a new prognostic model with
      these 4 factors. The new prognostic model showed better discriminative power
      compared with the classic IPI. Conclusion: Our new prognostic index model for
      DLBCL in the rituximab era has good discriminative power and is convenient to
      use.

PMID- 29333405
TI  - Primary central nervous system lymphoma: a new prognostic model for patients with
      diffuse large B-cell histology.
AB  - Background: Age and performance status are important prognostic factors in
      primary central nervous system (CNS) lymphoma. Although several prognostic models
      have been proposed, there is no consensus on the optimal model for patients with
      diffuse large B-cell histology. Methods: Seventy-seven patients with primary CNS
      diffuse large B-cell lymphoma were retrospectively analyzed to determine factors
      affecting survival. Three Western models were applied to our eligible patients;
      we devised a novel model based on our findings. Results: The median patient age
      was 59 years (range, 29-77); the median event-free and overall survival (OS)
      durations were 35.9 and 12.6 months, respectively. Nottingham/Barcelona and
      Memorial Sloan Kettering Cancer Center models were applicable to our cohorts.
      Multivariate analysis showed that advanced age, multifocal lesions, and high
      cerebrospinal fluid (CSF) protein concentrations were correlated significantly. A
      novel model for predicting prognosis was then developed based on these variables.
      Each variable was assigned 1 point; patients with a total score of 0, 1, 2, and 3
      were categorized into the low- (N=17), moderate- (N=26), high- (N=14), and very
      high-risk groups (N=4), respectively. Sixty-one patients were eligible
      considering our model; the median OS was 58.2, 34.8, 9.0, and 1.8 months in the
      low-, moderate-, high-, and very high-risk groups, respectively (P<0.01).
      Conclusion: Advanced age, multifocal lesions, and high CSF protein concentration
      were adversely related with prognosis. Our model can be helpful in pre-treatment
      risk stratification for patients with primary CNS lymphoma with diffuse large B
      cell histology.

PMID- 29333406
TI  - STAT3 expression is associated with poor survival in non-elderly adult patients
      with newly diagnosed multiple myeloma.
AB  - Background: Signal transducer and activator of transcription 3 (STAT3) is not
      only a key signaling molecule in the regulation of growth but is also involved in
      malignant transformation. We investigated the prognostic significance of STAT3
      expression in 94 non-elderly adult patients (aged 38 to 65 yr) with newly
      diagnosed multiple myeloma (MM). Methods: Tumor cell-specific phosphotyrosine
      STAT3 (PY-STAT3) expression at the time of diagnosis was evaluated with dual
      immunohistochemical (IHC) staining for PY-STAT3 and CD138. Results: PY-STAT3
      positivity was detected in 10 patients (10.6%), including three who showed strong
      expression. PY-STAT3-positive patients had higher serum C-reactive protein and
      calcium levels at diagnosis than did PY-STAT3-negative patients. PY-STAT3
      positivity had predictive value for poor progression-free survival (PFS; P=0.001)
      and overall survival (OS; P=0.003). Among the 60 patients who received frontline
      autologous stem cell transplantation, PY-STAT3-positive patients had poorer PFS
      than did PY-STAT3-negative patients (4.2 vs. 19.2 mo, respectively; P=0.013).
      Multivariate analysis identified PY-STAT3 expression as an independent prognostic
      factor for PFS (relative risk [RR]=2.706, P=0.014) and OS (RR=3.091, P=0.044).
      Conclusion: These data show that PY-STAT3 positivity, as determined using dual
      IHC, is a marker of poor prognosis in non-elderly adult patients with MM.

PMID- 29333407
TI  - The limited role of serum galactomannan assay in screening for invasive pulmonary
      aspergillosis in allogeneic stem cell transplantation recipients on micafungin
      prophylaxis: a retrospective study.
AB  - Background: We evaluated the outcomes of serum galactomannan (GM) assay for the
      screening of invasive pulmonary aspergillosis (IPA) in allogeneic hematopoietic
      stem cell transplantation (alloHSCT) recipients while on primary antifungal
      prophylaxis (PAP). Methods: This study included patients with hematologic
      disorders who underwent alloHSCT from January 2013 to November 2015. Patients
      received routine PAP with fluconazole before 2014 and micafungin after 2014;
      serum GM tests were performed and retrospectively analyzed. The sensitivity,
      specificity, positive predictive value (PPV), and negative predictive value (NPV)
      of serum GM tests for detection of probable/proven IPA were evaluated. The serial
      change of serum GM levels was illustrated on a time series plot. Results: A total
      of 136 alloHSCT recipients at Seoul National University Hospital were included in
      the study. Fluconazole was administered in 72 patients for PAP, while micafungin
      was administered in the remaining 64 patients. The overall sensitivity,
      specificity, and NPV of serum GM assays were 95.8% (95% confidence interval [CI]
      78.9-99.9%), 93.8% (95% CI 91.7-95.5%), and 99.8% (95% CI 99.1-100.0%),
      respectively. However, the PPV of GM tests was relatively low at 35.4% (95% CI
      23.9-48.2%). The serial change in serum GM levels differed according to the
      antifungal agents used. With effective PAP using micafungin, serial serum GM
      levels showed zero order kinetics during the neutropenic period. Conclusion:
      Although the serum GM assay is a sensitive and specific test for detecting IPA in
      alloHSCT recipients, its role for routine surveillance in an era of effective PAP
      with micafungin is limited.

PMID- 29333408
TI  - Is long term storage of cryopreserved stem cells for hematopoietic stem cell
      transplantation a worthwhile exercise in developing countries?
AB  - Background: Stem cell units (SCUs) that are cryopreserved prior to both
      autologous and allogeneic hematopoietic stem cell transplants (for donor
      lymphocyte infusion) remain unused or partially used several times, and become an
      increased burden to blood banks/SCU repositories. Because of the scarcity of data
      regarding the duration for which the storage is useful, there is no general
      consensus regarding disposal of SCUs. Methods: We conducted a retrospective audit
      of SCU utilization in 435 patients who planned to undergo either autologous stem
      cell transplantation (auto-SCT) (N=239) or allogeneic stem cell transplantation
      (allo-SCT) (N=196) at a tertiary cancer care center between November 2007 to
      January 2015. Results: Our cohort consisted of 1,728 SCUs stored for conducting
      auto-SCT and 729 SCUs stored for conducting donor lymphocyte infusions (DLIs)
      after allo-SCT. Stem cells were not infused in 12.5% of patients who had planned
      to undergo auto-SCT, and 80% of patients who underwent allo-SCT never received
      DLI. Forty-one percent of SCUs intended for use in auto-SCT remained unutilized,
      with a second auto-SCT being performed only in 4 patients. Ninety-four percent of
      SCUs intended for carrying out DLIs remained unused, with only minimal usage
      observed one year after undergoing allo-SCT. Conclusion: The duration of storage
      of unused SCUs needs to be debated upon, so that a consensus can be reached
      regarding the ethical disposal of SCU.

PMID- 29333409
TI  - Human parvovirus B19 and parvovirus 4 among Iranian patients with hemophilia.
AB  - Background: Human parvovirus B19 (B19V) is one of the smallest DNA viruses and
      shows great resistance to most disinfectants. Therefore, it is one of the common
      contaminant pathogens present in blood and plasma products. Parvovirus 4 (PARV4)
      is a newly identified parvovirus, which is also prevalent in parenteral
      transmission. In this study, we aimed to evaluate the prevalence of B19V and
      PARV4 DNA among patients with hemophilia in Birjand County in eastern Iran.
      Methods: This was a cross-sectional epidemiological study comprising nearly all
      people with hemophilia in this region. Whole blood samples were taken after
      patient registration and sent for plasma isolation. After nucleic acid
      extraction, B19V was detected with real-time polymerase chain reaction, PARV4 DNA
      was then detected using sensitive semi-nested PCR. Results: In total, there were
      86 patients with hemophilia, with mean age 28.5+/-1.5 years. Of these, 90.7% were
      men and 9.3% women; 84.9% had hemophilia A and 7.0% had hemophilia B. We found 11
      patients (12.8%) were positive for B19V DNA and 8 were positive (9.3%) for PARV4
      DNA. The prevalence of B19V was higher in middle-aged groups rather than younger
      people, whereas PARV4 infection was more common in younger patients (P <0.05).
      Conclusion: There was a high prevalence of B19V and PARV4 infection in this high
      risk group of patients with hemophilia. Due to the clinical significance of the
      B19 virus, imposing more precautionary measures for serum and blood products is
      recommended.

PMID- 29333410
TI  - Transplantation of human umbilical cord blood CD34+ cells into the liver of
      newborn NOD/SCID/IL-2Rgamma null (NSG) mice after busulfan conditioning.

PMID- 29333411
TI  - Successful treatment of a patient with myelodysplastic syndrome accompanied by
      pyoderma gangrenosum and Behcet's disease using allogeneic stem cell
      transplantation.

PMID- 29333412
TI  - Post-liver transplant myeloid maturation arrest.

PMID- 29333413
TI  - A case of primary plasma cell leukemia exhibiting hemophagocytic plasma cells
      relapsed with multiple cutaneous plasmacytoma.

PMID- 29333414
TI  - Differential diagnosis of primary cutaneous CD4+ small/medium T-cell
      lymphoproliferative lesions: A report of three cases.

PMID- 29333415
TI  - A young man with acute respiratory distress syndrome: eosinophilia is not always
      "benign".

PMID- 29333416
TI  - Does the c.-273T>C variant in the upstream region of the HBB gene cause a
      thalassemia phenotype?

PMID- 29333417
TI  - Comparison of the acute erythropoietic capacities of erythropoietin and U-74389G
      in terms of hemoglobin levels.

PMID- 29333418
TI  - Low-dose prednisolone in patients with paroxysmal nocturnal hemoglobinuria and
      inadequate response to eculizumab.

PMID- 29333419
TI  - Evaluation of a polyurethane foam dressing impregnated with 3% povidone-iodine
      (Betafoam) in a rat wound model.
AB  - Purpose: The purpose of this study was to evaluate the efficacy of Betafoam in
      terms of wound healing and safety. Methods: Fifty-four male adult Sprague-Dawley
      rats (weight, 200-250 g) were used in the study. Full-thickness skin defects were
      created on the back of each rats. The rats were assigned to 6 groups according to
      the type of wound dressing used (n = 9 for each group): Betafoam, Allevyn-Ag,
      Mepilex-Ag, Medifoam silver, Polymem-Ag, and gauze. The wound size, histological
      findings, and amount of DNA on the changed dressings for each group were analyzed
      and compared. Results: All groups showed an effective decrease in wound size.
      However, the differences between Betafoam and the other dressings were
      statistically significant on day 14 (P < 0.05). The number of newly generated
      blood vessels in the Betafoam group was significantly higher than in the gauze,
      Allevyn-Ag, and Medifoam silver groups (P < 0.001). In the Betafoam group, the
      proportion of collagen deposition was highest and showed a significantly superior
      arrangement of collagen fibers compared with the gauze, Allevyn-Ag, Mepilex-Ag,
      and Medifoam silver groups. The total content of the remaining DNA counts of the
      exchanged dressings were significantly lower in the Betafoam group than the
      others. Conclusion: Betafoam is effective in wound healing and provides the best
      performance amongst the various types of dressing materials in terms of re
      epithelialization, angiogenesis, collagen deposition, and tissue invasion.

PMID- 29333420
TI  - Technique for orthotopic liver transplantation in cynomolgus monkeys (Macaca
      fascicularis).
AB  - Purpose: Recent studies investigating new strategies to modulate the immune
      system have utilized animal models of liver transplantation (LT). However, the
      anhepatic phase (AHP) remains a crucial problem in LT. The aim of the present
      study is to introduce a technique for successful orthotopic LT in cynomolgus
      monkeys using an early-reperfusion strategy. Methods: Orthotopicallo-LT was
      performed with seven donor/recipient pairs of cynomolgus monkeys. Results: In 2
      recipients, liver allografts were perfused after suprahepatic inferior vena cava
      (SHIVC), portal vein (PV), and infrahepatic inferior vena cava (IHIVC)
      anastomosis. To reduce the time of AHP in five recipients, liver allografts ware
      perfused after SHIVC and PV anastomosis while the IHIVC was not anastomosed. In
      the latter strategy, the AHP was reduced from 46 minutes to 31 minutes and a 24
      hour survival rate of 80% was achieved. Conclusion: Our results indicate that an
      early-reperfusion strategy can be successfully used to establish a LT model in
      cynomolgus monkeys with a consistently high rate of animal survival.

PMID- 29333421
TI  - Brain metastasis from colorectal cancer: a single center experience.
AB  - Purpose: The detection rate of brain metastasis (BM) from colorectal cancer (CRC)
      is increasing. This study was designed to analyze the clinical features of BM and
      prognosis according to the therapeutic modalities. Methods: A total of 19 cases
      were collected in this study between November 2008 and December 2015. We reviewed
      the patients' demographic data and the clinical features of BM retrospectively
      and investigated their prognostic significance. Results: Nineteen patients
      included 8 male and 11 female patients. The median age at diagnosis of BM was
      62.4 years (range, 32-83 years). The median interval between diagnosis of CRC and
      BM was 39 months (range, 0-98 months). Eighteen patients (94.7%) had extracranial
      metastasis at the diagnosis of BM. Lung was the most common site of extracranial
      metastasis in 14 patients (73.7%). Synchronous BMs were found at the diagnosis of
      primary CRC in 2 patients (10.5%). The location of primary CRC was the colon in 6
      patients (31.6%) and the rectum in 13 patients (68.4%). At the diagnosis of BM,
      10 patients (52.6%) had a solitary BM. The common neurologic symptoms were
      headache in 8 cases (42.1%) and ataxia in 6 cases (31.6%). The median survival
      after the diagnosis of BM was 3 months (range, 1-10 months). The patients who
      underwent surgery plus stereotactic radiosurgery (SRS) had an improved survival
      (range, 3-10 months) than the other patients (range, 1-6 months) (P = 0.016).
      Conclusion: In patients with BM from CRC, surgical resection plus SRS might
      improve survival.

PMID- 29333422
TI  - Epigenetic inactivation of RUNX3 in colorectal cancer.
AB  - Purpose: Emerging evidence indicates that runt-related transcription factor 3
      (RUNX3) is an important tumor suppressor gene in several cancer types, including
      colorectal cancer (CRC). However, the clinical significance of RUNX3 inactivation
      in CRC remains unclear. The aim of this study was to examine the correlation
      between clinicopathologic factors and RUNX3 hypermethylation/expression in CRC.
      Methods: Sixty-two CRC patients who were treated at the Soonchunhyang University
      College of Medicine were recruited in this study. The hypermethylation of CpG
      islands in the RUNX3 promoter and the expression of RUNX3 mRNA were identified by
      methylation-specific polymerase chain reaction (PCR) and reverse transcriptase
      PCR, respectively. The expression of RUNX3 was determined by immunohistochemical
      staining. Results: Of the 62 CRC tissue samples, 20 (32.3%) presented
      hypermethylated RUNX3 promoters. Aberrant RUNX3 hypermethylation was found to be
      associated with vascular (P = 0.006) and lymphatic (P = 0.002) invasion.
      Hypermethylation of RUNX3 was associated with poor survival outcomes (P = 0.038).
      However, expression of RUNX3 was not a prognostic factor (P = 0.363). Conclusion:
      Hypermethylation of RUNX3 may be a predictor of a poor prognosis in CRC.

PMID- 29333423
TI  - Long-term outcomes after Natural Orifice Specimen Extraction versus conventional
      laparoscopy-assisted surgery for rectal cancer: a matched case-control study.
AB  - Purpose: The aim of this study was to compare the long-term outcomes of total
      laparoscopic surgery with Natural Orifice Specimen Extraction (NOSE) with those
      for conventional laparoscopy (CL)-assisted surgery for treating rectal cancers.
      Methods: We reviewed the prospectively collected records of 844 patients (163
      NOSE and 681 CL) who underwent curative surgery for mid- or upper rectal cancers
      from January 2006 to November 2012. We applied propensity score analyses and
      compared oncological outcomes for the NOSE and CL groups in a 1:1 matched cohort.
      Results: After propensity score matching, each group included 138 patients; the
      NOSE and CL groups did not differ significantly in terms of baseline clinical
      characteristics. The median follow-up was 57.7 months (interquartile range, 42.4
      82.5 months). The combined 5-year local recurrence rate for all tumor stages was
      4.1% (95% confidence interval [CI], 0.9%-7.4%) in the NOSE group and 3.0% (95%
      CI, 0%-6.3%) in the CL group (P = 0.355). The combined 5-year disease-free
      survival rates for all stages were 89.3% (95% CI, 84.3%-94.3%) in the NOSE group
      and 87.3% (95% CI, 81.8%-92.9%) in the CL group (P = 0.639). The postoperative
      mean fecal incontinence scores at 6, 12, and 24 months were similar between the 2
      groups. Conclusion: In our experience, NOSE for mid- and upper rectal cancer had
      acceptable long-term oncologic outcomes comparable to those of conventional
      minimal invasive surgery and seems to be a safe alternative to reduce access
      trauma.

PMID- 29333424
TI  - Anatomical distribution and detection rate of colorectal neoplasms according to
      age in the colonoscopic screening of a Korean population.
AB  - Purpose: Because data as a basis for the determination of proper age and modality
      for screening of colorectal neoplasms is lacking, we evaluated detection rates
      and anatomical distribution of colorectal neoplasms according to age in healthy
      individuals who underwent total colonoscopy for health checkup. Methods: A total
      of 16,100 cases that had received the colonoscopic examination from January to
      December in 2014 were analyzed. The total number of individuals who received
      total colonoscopy were divided by the number of individuals harboring colorectal
      adenoma to calculate the detection rate of colorectal adenoma. Individuals <=50
      years old were classified as young-age group and aged >50 were old-age group.
      Differences in anatomical locations of colorectal neoplasms were analyzed in the
      2 age groups by chi-square test. Risk factors for colorectal adenoma in each age
      group were analyzed using univariate and multivariate logistic regression
      analyses. Results: Detection rates of colorectal adenoma were 13.7% in all cases
      and 12.8% for those in their 40's. The main anatomical location of colorectal
      adenoma was proximal colon in both age groups (P < 0.001). Hyperplastic polyp was
      mainly distributed to the distal colon in both age groups (P < 0.001). Distal
      colon was the major site for colorectal cancer in the old-age group (P = 0.001).
      Proximal location of neoplasms was a risk factor for colorectal adenoma in both
      age groups with multivariate analysis. Conclusion: These data could be the bases
      for earlier initiation of screening for colorectal neoplasms with total
      colonoscopy to detect clinically significant colorectal polyps.

PMID- 29333425
TI  - Outcomes of selective surgery in patients with suspected small bowel injury from
      blunt trauma.
AB  - Purpose: The role of initial conservative therapy with selective surgery for
      patients with suspected blunt bowel injury by radiologic evaluation is less
      clear. The aim of the study is to assess the outcomes of patients who received
      initial conservative therapy with selective delayed surgery, compared to
      emergency surgery. Methods: During this 8-year study, a total of 77 patients who
      were hemodynamically stable were enrolled, in which computed tomography verified
      suspected bowel injury from blunt trauma (mesenteric hematoma, mesenteric fat
      infiltration, bowel wall thickening, and free fluid without solid organ injury)
      was managed with either initial conservative therapy with selective delayed
      surgery (group A; n = 42) or emergency surgery (group B; n = 35). The clinical
      outcomes including the rate of negative or nontherapeutic exploration and
      postoperative complications, between the groups were compared. Results: The
      enrolled patients had a mean age of 41 years including 51 men and 26 women. No
      difference in the clinical characteristics was found between the groups. In group
      A, 18 patients underwent delayed surgery and 24 recovered without surgery. Among
      patients who underwent surgery, 3 (17%) underwent negative or nontherapeutic
      explorations. In group B, 13 (37%) underwent negative or nontherapeutic
      explorations. Postoperative complications occurred in 21 patients and there was
      no difference between the groups. Conclusion: Initial conservative therapy with
      selective delayed surgery did not increased severe postoperative complications
      and had a low rate of negative or nontherapeutic surgical explorations in
      hemodynamically stable patients with suspected blunt bowel injury.

PMID- 29333427
TI  - Surgery of multiple lymphangioma in small bowel: a rare case report of chronic
      gastrointestinal bleeding.
AB  - Small bowel lymphangioma is a rare benign tumor of the lymphatic system,
      characterized by the presence of dilated lymphatic spaces and significant
      gastrointestinal bleeding. Small bowel lymphangiomas are rare in adults and case
      reports are few. Lymphangiomas in the jejunum or ileum are extremely rare and
      account for less than 1% of all lymphangiomas. The case reported herein is of an
      older patient (70-year-old male) with melena and chronic anemia (hemoglobin count
      < 5 g/dL) who had small-sized multiple lymphangiomas in his small bowel
      (jejunum). Surgical resection was performed after failure of treatment by
      gastroenteroscopy. Final pathological analysis revealed lymphangioma with
      thrombus and hemorrhage. After surgery, he no longer had decreased hemoglobin
      count, nor symptoms of anemia and melena. Also, at the last follow-up visit, the
      patient's hemoglobin count patient was normal and he returned to normal daily
      functions.

PMID- 29333426
TI  - Are you prepared for pancreas bifidum? A case report.
AB  - Pancreas divisum-failure of fusion of the dorsal and ventral pancreatic ducts-is
      relatively well known as the most common congenital anomaly of the pancreatic
      duct, of with an incidence approximately 10% of all embryos. And there is a rare
      anomaly similar to pancreas divisum in which doubled ducts are formed. This
      condition is a rare developmental anomaly called pancreas bifidum or bifid
      pancreas or fish tail pancreas. This report describes a patient with pancreas
      bifidum who had 2 separated ducts within the pancreas from tail to neck but did
      not have a separated parenchyma. We hope that this report helps pancreatic
      surgeons to have knowledge of pancreas bifidum and helps them to be prepared for
      this anatomical variant.

PMID- 29333428
TI  - The Effect of Prucalopride on Small Bowel Transit Time in Hospitalized Patients
      Undergoing Capsule Endoscopy.
AB  - Background: The inpatient status is a well-known risk factor for incomplete video
      capsule endoscopy (VCE) examinations due to prolonged transit time. We aimed to
      evaluate the effect of prucalopride on small bowel transit time for hospitalized
      patients undergoing VCE. Methods: We included all hospitalized patients who
      underwent VCE at a tertiary academic center from October 2011 through September
      2016. A single 2 mg dose of prucalopride was given exclusively for all patients
      who underwent VCE between March 2014 and December 2015. VCE studies were excluded
      if the capsule was retained or endoscopically placed, if other prokinetic agents
      were given, in cases with technical failure, or if patients had prior gastric or
      small bowel resection. Results: 442 VCE were identified, of which 68 were
      performed in hospitalized patients. 54 inpatients were included, of which 29
      consecutive patients received prucalopride. The prucalopride group had a
      significantly shorter small bowel transit time compared to the control group (92
      versus 275.5, p < 0.001). There was a trend for a higher completion rate in the
      prucalopride group (93.1% versus 76%, p = 0.12). Conclusions: Our results suggest
      that the administration of prucalopride prior to VCE is a simple and effective
      intervention to decrease small bowel transit time.

PMID- 29333429
TI  - Screening of Lipid Composition for Scalable Fabrication of Solvent-Free Lipid
      Microarrays.
AB  - Liquid microdroplet arrays on surfaces are a promising approach to the
      miniaturization of laboratory processes such as high-throughput screening. The
      fluid nature of these droplets poses unique challenges and opportunities in their
      fabrication and application, particularly for the scalable integration of
      multiple materials over large areas and immersion into cell culture solution.
      Here, we use pin spotting and nanointaglio printing to screen a library of lipids
      and their mixtures for their compatibility with these fabrication processes, as
      well as stability upon immersion into aqueous solution. More than 200
      combinations of natural and synthetic oils composed of fatty acids,
      triglycerides, and hydrocarbons were tested for their pin-spotting and
      nanointaglio print quality and their ability to contain the fluorescent compound
      tetramethylrhodamine B isothiocyanate (TRITC) upon immersion in water. A
      combination of castor oil and hexanoic acid at the ratio of 1:1 (w/w) was found
      optimal for producing reproducible patterns that are stable upon immersion into
      water. This method is capable of large-scale nanomaterials integration.

PMID- 29333432
TI  - Cytomegalovirus-associated pulmonary exacerbation in patients with cystic
      fibrosis.
AB  - CMV is an unusual cause of pulmonary exacerbation in immunocompetent individuals
      with CF http://ow.ly/Rdds30hlnjV.

PMID- 29333431
TI  - Morphology Changes in Human Fungal Pathogens upon Interaction with the Host.
AB  - Morphological changes are a very common and effective strategy for pathogens to
      survive in the mammalian host. During interactions with their host, human
      pathogenic fungi undergo an array of morphological changes that are tightly
      associated with virulence. Candida albicans switches between yeast cells and
      hyphae during infection. Thermally dimorphic pathogens, such as Histoplasma
      capsulatum and Blastomyces species transform from hyphal growth to yeast cells in
      response to host stimuli. Coccidioides and Pneumocystis species produce spherules
      and cysts, respectively, which allow for the production of offspring in a
      protected environment. Finally, Cryptococcus species suppress hyphal growth and
      instead produce an array of yeast cells-from large polyploid titan cells to micro
      cells. While the morphology changes produced by human fungal pathogens are
      diverse, they all allow for the pathogens to evade, manipulate, and overcome host
      immune defenses to cause disease. In this review, we summarize the morphology
      changes in human fungal pathogens-focusing on morphological features, stimuli,
      and mechanisms of formation in the host.

PMID- 29333433
TI  - Vitamin D Receptor Gene Polymorphisms Influence T1D Susceptibility among
      Pakistanis.
AB  - Background: The vitamin D receptor (VDR) gene regulates insulin secretion from
      the pancreas and acts as a mediator of the immune response through vitamin D.
      Polymorphism in VDR causes alterations in the functioning of vitamin D, leading
      to type 1 diabetes (T1D) predisposition. The aim of the present study was to
      determine VDR gene polymorphism in association with T1D in Pakistanis. Methods:
      The association was evaluated by selecting rs2228570 (FokIota), rs7975232
      (ApaIota), and rs731236 (TaqIota) polymorphic sites in 102 patients and 100
      controls. Genotypes were identified by DNA sequencing and PCR-RFLP. Results: The
      allelic and genotypic frequencies of FokIota and ApaI were significantly
      associated with T1D (p < 0.001) development. At the FokIota site, tryptophan was
      replaced with arginine due to polymorphism. A novel SNP (GeneBank acc number
      KT280406) was identified through the sequencing of intron 8, 62 bp downstream
      from the ApaI polymorphic site, and significantly associated with T1D
      development. The TaqIota did not depict any association with T1D at the allelic
      or genotypic level (p > 0.05). CCGC, CCGG, CCTC, and CCTG haplotypes were
      significantly associated with disease development (p < 0.05). However, CTGG
      haplotype was protective towards T1D (p < 0.01). Conclusion: VDR polymorphisms
      were identified as susceptible regions for T1D development in the Pakistani
      population.

PMID- 29333430
TI  - Adaptive Immunity to Cryptococcus neoformans Infections.
AB  - The Cryptococcus neoformans/Cryptococcus gattii species complex is a group of
      fungal pathogens with different phenotypic and genotypic diversity that cause
      disease in immunocompromised patients as well as in healthy individuals. The
      immune response resulting from the interaction between Cryptococcus and the host
      immune system is a key determinant of the disease outcome. The species C.
      neoformans causes the majority of human infections, and therefore almost all
      immunological studies focused on C. neoformans infections. Thus, this review
      presents current understanding on the role of adaptive immunity during C.
      neoformans infections both in humans and in animal models of disease.

PMID- 29333435
TI  - Enhancement of Nucleoside Production in Hirsutella sinensis Based on Biosynthetic
      Pathway Analysis.
AB  - To enhance nucleoside production in Hirsutella sinensis, the biosynthetic
      pathways of purine and pyrimidine nucleosides were constructed and verified. The
      differential expression analysis showed that purine nucleoside phosphorylase,
      inosine monophosphate dehydrogenase, and guanosine monophosphate synthase genes
      involved in purine nucleotide biosynthesis were significantly upregulated 16.56
      fold, 8-fold, and 5.43-fold, respectively. Moreover, dihydroorotate
      dehydrogenase, uridine nucleosidase, uridine/cytidine monophosphate kinase, and
      inosine triphosphate pyrophosphatase genes participating in pyrimidine nucleoside
      biosynthesis were upregulated 4.53-fold, 10.63-fold, 4.26-fold, and 5.98-fold,
      respectively. To enhance the nucleoside production, precursors for synthesis of
      nucleosides were added based on the analysis of biosynthetic pathways. Uridine
      and cytidine contents, respectively, reached 5.04 mg/g and 3.54 mg/g when adding
      2 mg/mL of ribose, resulting in an increase of 28.6% and 296% compared with the
      control, respectively. Meanwhile, uridine and cytidine contents, respectively,
      reached 10.83 mg/g 2.12 mg/g when adding 0.3 mg/mL of uracil, leading to an
      increase of 176.3% and 137.1%, respectively. This report indicated that
      fermentation regulation was an effective way to enhance the nucleoside production
      in H. sinensis based on biosynthetic pathway analysis.

PMID- 29333437
TI  - A Key Major Guideline for Engineering Bioactive Multicomponent
      Nanofunctionalization for Biomedicine and Other Applications: Fundamental Models
      Confirmed by Both Direct and Indirect Evidence.
AB  - This paper deals with the engineering multicomponent nanofunctionalization
      process considering fundamental physicochemical features of nanostructures such
      as surface energy, chemical bonds, and electrostatic interactions. It is pursued
      by modeling the surface nanopatterning and evaluating the proposed technique and
      the models. To this end, the effects of surface modifications of nanoclay on
      surface interactions, orientations, and final features of TiO2/Mt nanocolloidal
      textiles functionalization have been investigated. Various properties of cross
      linkable polysiloxanes (XPs) treated samples as well as untreated samples with
      XPs have been compared to one another. The complete series of samples have been
      examined in terms of bioactivity and some physical properties, given to provide
      indirect evidence on the surface nanopatterning. The results disclosed a key role
      of the selected factors on the final features of treated surfaces. The effects
      have been thoroughly explained and modeled according to the fundamental
      physicochemical features. The developed models and associated hypotheses
      interestingly demonstrated a full agreement with all measured properties and were
      appreciably confirmed by FESEM evidence (direct evidence). Accordingly, a
      guideline has been developed to facilitate engineering and optimizing the pre-,
      main, and post-multicomponent nanofunctionalization procedures in terms of
      fundamental features of nanostructures and substrates for biomedical applications
      and other approaches.

PMID- 29333436
TI  - Behavioural and Autonomic Regulation of Response to Sensory Stimuli among
      Children: A Systematic Review of Relationship and Methodology.
AB  - Background: Previous studies have explored the correlates of behavioural and
      autonomic regulation of response to sensory stimuli in children; however, a
      comprehensive review of such relationship is lacking. This systematic review was
      performed to critically appraise the current evidence on such relationship and
      describe the methods used in these studies. Methods: Online databases were
      systematically searched for peer-reviewed, full-text articles in the English
      language between 1999 and 2016, initially screened by title and abstract, and
      appraised and synthesized by two independent review authors. Results: Fourteen
      Level III-3 cross-sectional studies were included for systematic review, among
      which six studies explored the relationship between behaviour and physiological
      regulation of responses to sensory stimuli. Three studies reported significant
      positive weak correlations among ASD children; however, no correlations were
      found in typically developing children. Methodological differences related to
      individual differences among participants, measures used, and varied laboratory
      experimental setting were noted. Conclusion: This review suggests inconclusive
      evidence supporting the relationship between behavioural and physiological
      regulation of responses to sensory stimuli among children. Methodological
      differences may likely have confounded the results of the current evidence. We
      present methodological recommendations to address this matter for future
      researches. This trial is registered with PROSPERO registration number
      CRD42016043887.

PMID- 29333434
TI  - CONSERVED AND EXAPTED FUNCTIONS OF NUCLEAR RECEPTORS IN ANIMAL DEVELOPMENT.
AB  - The nuclear receptor gene family includes 18 members that are broadly conserved
      among multiple disparate animal phyla, indicating that they trace their
      evolutionary origins to the time at which animal life arose. Typical nuclear
      receptors contain two major domains: a DNA-binding domain and a C-terminal domain
      that may bind a lipophilic hormone. Many of these nuclear receptors play varied
      roles in animal development, including coordination of life cycle events and
      cellular differentiation. The well-studied genetic model systems of Drosophila,
      C. elegans, and mouse permit an evaluation of the extent to which nuclear
      receptor function in development is conserved or exapted (repurposed) over animal
      evolution. While there are some specific examples of conserved functions and
      pathways, there are many clear examples of exaptation. Overall, the evolutionary
      theme of exaptation appears to be favored over strict functional conservation.
      Despite strong conservation of DNA-binding domain sequences and activity, the
      nuclear receptors prove to be highly-flexible regulators of animal development.

PMID- 29333438
TI  - Effect of Endogenous Arginine-Vasopressin Arising from the Paraventricular
      Nucleus on Learning and Memory Functions in Vascular Dementia Model Rats.
AB  - The hippocampus is a key structure for encoding and processing memory and for
      spatial orientation, which are among the cognitive functions most sensitive to
      cerebral ischemia, hypoxia, and vascular dementia (VD). Since hippocampal
      formation is one of the principle forebrain targets for arginine-vasopressin
      (AVP) innervations arising in the hypothalamic paraventricular nucleus (PVN), we
      explored the contributions of AVP to VD pathogenesis. To this end, we randomly
      assigned pathogen-free, male Wistar rats to one of seven groups in a VD model and
      tested AVP treatment effects on spatial learning and memory using the Morris
      water maze. We also measured the superoxide dismutase (SOD) activity and
      malondialdehyde (MDA) concentration in brain samples and monitored the expression
      of AVP-positive neurons in the hippocampus by immunohistochemistry. The VD model
      with repeated cerebral ischemia-reperfusion injury evoked impairment of cognitive
      function and reduced cerebral concentrations of the antioxidation markers.
      Lesioning the rat PVN showed a similar effect on learning and memory and reduced
      antioxidation markers in the brain tissue. However, AVP injection into the PVN
      improved cognitive performance in VD rats, while enhancing/rectifying the changes
      in antioxidation markers. We conclude that our VD model may decrease AVP
      secretion in the PVN and subsequently reduce antioxidant capacity in the
      hippocampus, leading to impaired cognitive function.

PMID- 29333439
TI  - Cloning, Expression, and Immunogenicity of Fimbrial-F17A Subunit Vaccine against
      Escherichia coli Isolated from Bovine Mastitis.
AB  - There is a need to identify and select new promising immunodominant antigens that
      have the ability to provide protective immunity against E. coli causing bovine
      mastitis. Recently we showed that f17a was found to be the most prevalent and
      crucial virulent factor among the pathogenic E. coli isolated from bovine
      mastitis. Here, in this report, the recombinant F17A based subunit vaccine
      adjuvant with MF59 was tested for immunogenicity against E. coli in a murine
      model. The vaccinated mice did not show any abnormal behavioral changes and
      histopathological lesions after vaccination. The specific antibody level against
      F17A was significantly higher in MF59-adjuvant-group, and also lasted for longer
      duration with a significant (P < 0.01) production level of IgG1 and IgG2a.
      Moreover, we noted higher survival rate in mice injected with F17A-MF59-adjuvant
      group after challenging with the clinical E. coli strain. Our findings of
      bacterial clearance test revealed that elimination rate from liver, spleen, and
      kidney in MF59-adjuvant-group was significantly higher than the control group.
      Finally, the proportion of CD4+T cells was increased, while CD8+ was decreased in
      MF59-adjuvant group. In conclusion, the current study reveals the capability of
      F17A-MF59 as a potential vaccine candidate against pathogenic E. coli causing
      mastitis in dairy animals.

PMID- 29333440
TI  - Erratum to "Collagen Sponge Functionalized with Chimeric Anti-BMP-2 Monoclonal
      Antibody Mediates Repair of Critical-Size Mandibular Continuity Defects in a
      Nonhuman Primate Model".
AB  - [This corrects the article DOI: 10.1155/2017/8094152.].

PMID- 29333441
TI  - Corrigendum to "Safety and Clinical Usage of Newcastle Disease Virus in Cancer
      Therapy".
AB  - [This corrects the article DOI: 10.1155/2011/718710.].

PMID- 29333442
TI  - Characterisation of Casein Kinase 1.1 in Leishmania donovani Using the CRISPR
      Cas9 Toolkit.
AB  - The recent adaptation of CRISPR Cas9 genome editing to Leishmania spp. has opened
      a new era in deciphering Leishmania biology. The method was recently improved
      using a PCR-based CRISPR Cas9 approach, which eliminated the need for cloning.
      This new approach, which allows high-throughput gene deletion, was successfully
      validated in L. mexicana and L. major. In this study, we validated the toolkit in
      Leishmania donovani targeting the flagellar protein PF16, confirming that the
      tagged protein localizes to the flagellum and that null mutants lose their
      motility. We then used the technique to characterise CK1.1, a member of the
      casein kinase 1 family, which is involved in the regulation of many cellular
      processes. We showed that CK1.1 is a low-abundance protein present in
      promastigotes and in amastigotes. We demonstrated that CK1.1 is not essential for
      promastigote and axenic amastigote survival or for axenic amastigote
      differentiation, although it may have a role during stationary phase. Altogether,
      our data validate the use of PCR-based CRISPR Cas9 toolkit in L. donovani, which
      will be crucial for genetic modification of hamster-derived, disease-relevant
      parasites.

PMID- 29333443
TI  - Tumor Necrosis Factor-Like Weak Inducer of Apoptosis Activates Type I Interferon
      Signals in Lupus Nephritis.
AB  - Type I interferon (IFN) plays a central role in pathogenesis of systemic lupus
      erythematosus (SLE); tumor necrosis factor-like weak inducer of apoptosis (TWEAK)
      has been associated with a pathogenic role in lupus nephritis (LN). Thus we
      investigated whether TWEAK could induce the activation of type I IFN pathway in
      LN. We examined this in patient-derived peripheral blood mononuclear cells
      (PBMCs) as well as MRL/lpr mice, a murine LN model. Relative to the control
      cohorts, MRL/lpr mice showed severe histological changes, high index levels of
      renal damage, and elevated expression of type I IFN-inducible genes. After shRNA
      suppression of TWEAK, we observed that renal damage was significantly attenuated
      and expression of type I IFN-inducible genes was reduced in MRL/lpr mice. In
      parallel, siRNA of TWEAK also significantly reduced the expression of type I IFN
      inducible genes in PBMCs relative to control transfections. In PBMCs, TWEAK
      stimulation also led to expression of type I IFN-inducible genes. Our results
      illustrate a novel regulatory role of TWEAK, in which its activity positively
      regulates type I IFN pathway in LN based on preclinical models. Our findings
      suggest TWEAK could act as a critical target in preventing renal damage in
      patients with LN.

PMID- 29333444
TI  - MicroRNA-31 Function as a Suppressor Was Regulated by Epigenetic Mechanisms in
      Gastric Cancer.
AB  - Gastric cancer is one of the most lethal malignancies worldwide. The aberrant
      expression of microRNA-31 (miR-31) has been reported in gastric cancer; however,
      its regulation mechanisms are still unclear. Here, we confirmed that miR-31
      expression was significantly decreased in gastric cancer tissue and cell lines.
      Ectopic expression of miR-31 potentially suppresses proliferation and induced
      early apoptosis in gastric cancer cells. Furthermore, miR-31 expression was
      regulated as a result of epigenetic mechanisms. The downregulation of miR-31 was
      associated with promoter DNA methylation status in gastric cancer and cell lines.
      Moreover, we found that HDAC2 was the direct target of miR-31 by binding to 3'
      UTR from the results of luciferase reporter assays, qRT-PCR, and western
      blotting. HDAC2 played an activation role in tumor growth, whose expression is
      upregulated and inversely associated with miR-31 levels. All the results
      suggested that miR-31 function as a crucial tumor suppressor was regulated by
      epigenetic mechanisms in gastric cancer. We found an epigenetic pathway loop, DNA
      methylation-miRNA expression-target gene-tumor progression in gastric cancer, and
      also provided implications for molecular diagnosis and therapeutics of gastric
      malignancies by detecting miR-31 as a potential target.

PMID- 29333445
TI  - Retrograde Activation of the Extrinsic Apoptotic Pathway in Spinal-Projecting
      Neurons after a Complete Spinal Cord Injury in Lampreys.
AB  - Spinal cord injury (SCI) is a devastating condition that leads to permanent
      disability because injured axons do not regenerate across the trauma zone to
      reconnect to their targets. A prerequisite for axonal regeneration will be the
      prevention of retrograde degeneration that could lead to neuronal death. However,
      the specific molecular mechanisms of axotomy-induced degeneration of spinal
      projecting neurons have not been elucidated yet. In lampreys, SCI induces the
      apoptotic death of identifiable descending neurons that are "bad
      regenerators/poor survivors" after SCI. Here, we investigated the apoptotic
      process activated in identifiable descending neurons of lampreys after SCI. For
      this, we studied caspase activation by using fluorochrome-labeled inhibitors of
      caspases, the degeneration of spinal-projecting neurons using Fluro-Jade C
      staining, and the involvement of the intrinsic apoptotic pathway by means of
      cytochrome c and Valpha double immunofluorescence. Our results provide evidence
      that, after SCI, bad-regenerating spinal cord-projecting neurons slowly
      degenerate and that the extrinsic pathway of apoptosis is involved in this
      process. Experiments using the microtubule stabilizer Taxol showed that caspase-8
      signaling is retrogradely transported by microtubules from the site of axotomy to
      the neuronal soma. Preventing the activation of this process could be an
      important therapeutic approach after SCI in mammals.

PMID- 29333446
TI  - Adaptation and Validation of the Foot Function Index-Revised Short Form into
      Polish.
AB  - Purpose: The aim of the present study was to adapt the Foot Function Index
      Revised Short Form (FFI-RS) questionnaire into Polish and verify its reliability
      and validity in a group of patients with rheumatoid arthritis (RA). Methods: The
      study included 211 patients suffering from RA. The FFI-RS questionnaire underwent
      standard linguistic adaptation and its psychometric parameters were investigated.
      The enrolled participants had been recruited for seven months as a convenient
      sample from the rheumatological hospital in Srem (Poland). They represented
      different sociodemographic characteristics and were characterized as rural and
      city environments residents. Results: The mean age of the patients was 58.9 +/-
      10.2 years. The majority of patients (85%) were female. The average final FFI-RS
      score was 62.9 +/- 15.3. The internal consistency was achieved at a high level of
      0.95 in Cronbach's alpha test, with an interclass correlation coefficient ranging
      between 0.78 and 0.84. A strong correlation was observed between the FFI-RS and
      Health Assessment Questionnaire-Disability Index (HAQ-DI) questionnaires.
      Conclusion: The Polish version of FFI-RS-PL indicator is an important tool for
      evaluating the functional condition of patients' feet and can be applied in the
      diagnosis and treatment of Polish-speaking patients suffering from RA.

PMID- 29333447
TI  - Comparison of Different Contrast Agents in Detecting Cardiac Right-to-Left Shunt
      in Patients with a Patent Foramen Ovale during Contrast-Transthoracic
      Echocardiography.
AB  - The aim of this study is to evaluate the ability of two different contrast agents
      to detect cardiac right-to-left shunting in patients with a patent foramen ovale
      during contrast transthoracic echocardiography and transesophageal
      echocardiography. Eighty-four patients who had migraines or experienced
      cryptogenic stroke were prospectively enrolled. Contrast echocardiography of the
      right portion of the heart was performed using an injection of either (i) 8 ml of
      agitated saline, 1 ml of blood, and 1 ml of air (ASB) or (ii) 4 ml of vitamin B6
      and 6 ml of sodium bicarbonate solution (VSBS). All patients underwent contrast
      echocardiography with different contrast agents successively before undergoing
      transesophageal echocardiography. The diagnostic sensitivity of VSBS and ASB for
      cardiac shunting diagnosis was 94.23% and 78.85%, respectively. The diagnostic
      sensitivity in the VSBS group was significantly higher than that in the ASB group
      (chi2 = 5.283, P = 0.022). The observed semiquantitative shunt grading suggests
      that the positive rate in the VSBS group was higher than that in the ASB group (Z
      = -1.998, P = 0.046). The use of vitamin B6 and sodium bicarbonate solution as a
      TTE contrast agent yielded a high sensitivity compared with ASB. However, further
      trials with large sample size are required to confirm this finding.

PMID- 29333448
TI  - Comparison of Monolateral External Fixation and Internal Fixation for Skeletal
      Stabilisation in the Management of Small Tibial Bone Defects following Successful
      Treatment of Chronic Osteomyelitis.
AB  - Background: To compare the salvage rate and complication between internal
      fixation and external fixation in patients with small bone defects caused by
      chronic infectious osteomyelitis debridement. Methods: 125 patients with chronic
      infectious osteomyelitis of tibia fracture who underwent multiple irrigation,
      debridement procedure, and local/systemic antibiotics were enrolled. Bone
      defects, which were less than 4 cm, were treated with bone grafting using either
      internal fixation or monolateral external fixation. 12-month follow-up was
      conducted with an interval of 3 months to evaluate union of bone defect. Results:
      Patients who underwent monolateral external fixation had higher body mass index
      and fasting blood glucose, longer time since injury, and larger bone defect
      compared with internal fixation. No significant difference was observed in
      incidence of complications (23.5% versus 19.3%), surgery time (156 +/- 23 minutes
      versus 162 +/- 21 minutes), and time to union (11.1 +/- 3.0 months versus 10.9 +/
      3.1 months) between external fixation and internal fixation. Internal fixation
      had no significant influence on the occurrence of postoperation complications
      after multivariate adjustment when compared with external fixation. Furthermore,
      patients who underwent internal fixation experienced higher level of daily living
      scales and lower level of anxiety. Conclusions: It was relatively safe to use
      internal fixation for stabilization in osteomyelitis patients whose bone defects
      were less than 4 cm and infection was well controlled.

PMID- 29333449
TI  - The Root Membrane Technique: Human Histologic Evidence after Five Years of
      Function.
AB  - Background: The "root membrane" (RM) is a technique that has become popular among
      implantologists for placement of immediate implants in the anterior maxilla.
      Purpose: To present histologic evidence of an immediate implant placed in the
      human anterior maxilla, according to the RM technique, and retrieved after five
      years. Methods: A fixture, along with the surrounding tissues, was retrieved from
      the anterior maxilla of a 68-year-old patient, who had been treated five years
      earlier with immediate implant placement and RM technique. The specimen was
      processed for histologic/histomorphometric evaluation. Results: The buccal bone
      plate was maintained without any resorption; a healthy periodontal ligament was
      evidenced. The implant showed osseointegration, with a high percentage of bone-to
      implant contact (BIC = 76.2%). With regard to the space between the RM and the
      implant, the apical and medial thirds were filled with compact, mature bone; the
      coronal third was colonized by noninfiltrated connective tissue. Conclusions: The
      RM technique appears to be effective in preventing bone resorption of the buccal
      bone plate of the human anterior maxilla, five years after the placement of an
      immediate implant.

PMID- 29333450
TI  - RBP4: A Culprit for Insulin Resistance in End Stage Renal Disease That Can Be
      Cleared by Hemodiafiltration.
AB  - Introduction: Retinol Binding Protein 4 (RBP4) is mainly excreted by the kidney
      and plays a pivotal role in insulin resistance (IR). In our study, we evaluated
      the association between RBP4 and IR in hemodialysis subjects (HD). We also
      assessed how circulating RBP4 could be influenced by kidney transplant or
      different dialytic techniques. Methods: RBP4 serum levels were evaluated in HD (n
      = 16) and matched healthy controls (C; n = 16). RBP4 and glucose transporter type
      4 (GLUT4) mRNA expressions were also determined in adipose tissue. Circulating
      RBP4 was evaluated after kidney transplant (n = 7) and in hemodialysis patients
      (n = 10) enrolled in a cross-over study treated with standard bicarbonate
      dialysis (BD) or hemodiafiltration (HDF). Results: HOMA index (P < 0.05) and
      serum RBP4 (P < 0.005) were higher in HD compared to C. RBP4 levels positively
      correlated with fasting serum glucose (P < 0.05). RBP4 mRNA was lower in HD
      compared to C (P < 0.05) and positively correlated with kidney function (P <
      0.05) and GLUT4 mRNA (P < 0.001). Transplant or HDF reduced circulating RBP4 (P <
      0.01 and P < 0.05, resp.). Our results demonstrate that IR is associated with
      high circulating RBP4 and that suppressed RBP4 adipose tissue expression is
      accompanied by reduced GLUT4 expression in HD. Renal transplantation or HDF are
      effective in lowering serum RBP4 levels.

PMID- 29333452
TI  - Jail Diversion for Persons with Serious Mental Illness Coordinated by a
      Prosecutor's Office.
AB  - Persons with serious mental illnesses (SMI) are involved in the criminal justice
      system at a disproportionately higher rate than the general population. While the
      exact causes remain unclear, it is accepted that a comprehensive strategy
      including mental health treatment is needed to reduce recidivism. This paper
      describes a unique jail diversion program coordinated by a county prosecutor's
      office in which individuals were diverted towards mental health services
      including case management, community-based services, and housing supports.
      Outcomes were studied over a five-year period, beyond the typical 12- to 24-month
      follow-up in other studies. Individuals who completed the program, compared to
      those who did not complete it, were at lower risk for being rearrested, arrested
      fewer times, and incarcerated fewer days. Gains were moderated by previous
      criminal justice involvement and substance use but, nevertheless, were maintained
      despite severity of history. The strongest gains were seen while the individual
      was still actively enrolled in the diversion services and these outcomes were
      maintained for up to four years. These findings suggest that completion of a jail
      diversion program facilitated by a prosecutor's office can lower recidivism and
      days incarcerated. Further research is needed to assess the unique contribution
      of prosecutor office facilitation.

PMID- 29333451
TI  - Purification, Characterization, and Mode of Action of Pentocin JL-1, a Novel
      Bacteriocin Isolated from Lactobacillus pentosus, against Drug-Resistant
      Staphylococcus aureus.
AB  - Staphylococcus aureus and its drug-resistant strains, which threaten public
      health and food safety, are in need of effective control by biopreservatives. A
      novel bacteriocin, pentocin JL-1, produced by Lactobacillus pentosus that was
      isolated from the intestinal tract of Chiloscyllium punctatum, was purified by a
      four-step chromatographic process. Mass spectrometry based on MALDI-TOF indicated
      that pentocin JL-1 has a molecular mass of 2987.23 Da. Only six of the twenty
      five amino acids could be identified by Edman degradation. This bacteriocin is
      thermostable and tolerates a pH range of 5-7. Also, it is sensitive to proteinase
      K, trypsin, pepsin, and alkaline protease. This bacteriocin has a broad
      inhibitory spectrum against both Gram-positive and Gram-negative strains and in
      particular is effective against multidrug-resistant S. aureus. Additionally, we
      showed that the cell membrane is the target of pentocin JL-1 against methicillin
      resistant S. aureus (MRSA), causing a loss of proton motive force. Furthermore,
      pentocin JL-1 has a drastic impact on the structure and integrity of MRSA cells.
      These results suggest that pentocin JL-1 has potential as a biopreservative in
      the food industry.

PMID- 29333453
TI  - Hibiscus syriacus Extract from an Established Cell Culture Stimulates Skin Wound
      Healing.
AB  - Higher plants are the source of a wide array of bioactive compounds that support
      skin integrity and health. Hibiscus syriacus, family Malvaceae, is a plant of
      Chinese origin known for its antipyretic, anthelmintic, and antifungal
      properties. The aim of this study was to assess the healing and hydration
      properties of H. syriacus ethanolic extract (HSEE). We established a cell culture
      from Hibiscus syriacus leaves and obtained an ethanol soluble extract from
      cultured cells. The properties of the extract were tested by gene expression and
      functional analyses on human fibroblast, keratinocytes, and skin explants. HSEE
      treatment increased the healing potential of fibroblasts and keratinocytes.
      Specifically, HSEE significantly stimulated fibronectin and collagen synthesis by
      16 and 60%, respectively, while fibroblasts contractility was enhanced by 30%.
      These results were confirmed on skin explants, where HSEE accelerated the wound
      healing activity in terms of epithelium formation and fibronectin production.
      Moreover, HSEE increased the expression of genes involved in skin hydration and
      homeostasis. Specifically, aquaporin 3 and filaggrin genes were enhanced by 20
      and 58%, respectively. Our data show that HSEE contains compounds capable of
      stimulating expression of biomarkers relevant to skin regeneration and hydration
      thereby counteracting molecular pathways leading to skin damage and aging.

PMID- 29333455
TI  - Molecular and Cellular Mechanisms of Neuroinflammation.

PMID- 29333454
TI  - Virtual Reality Telerehabilitation for Postural Instability in Parkinson's
      Disease: A Multicenter, Single-Blind, Randomized, Controlled Trial.
AB  - Introduction: Telerehabilitation enables patients to access remote rehabilitation
      services for patient-physiotherapist videoconferencing in their own homes. Home
      based virtual reality (VR) balance training has been shown to reduce postural
      instability in patients with Parkinson's disease (PD). The primary aim was to
      compare improvements in postural stability after remotely supervised in-home VR
      balance training and in-clinic sensory integration balance training (SIBT).
      Methods: In this multicenter study, 76 PD patients (modified Hoehn and Yahr
      stages 2.5-3) were randomly assigned to receive either in-home VR
      telerehabilitation (n = 38) or in-clinic SIBT (n = 38) in 21 sessions of 50
      minutes each, 3 days/week for 7 consecutive weeks. VR telerehabilitation
      consisted of graded exergames using the Nintendo Wii Fit system; SIBT included
      exercises to improve postural stability. Patients were evaluated before
      treatment, after treatment, and at 1-month follow-up. Results: Analysis revealed
      significant between-group differences in improvement on the Berg Balance Scale
      for the VR telerehabilitation group (p = 0.04) and significant Time * Group
      interactions in the Dynamic Gait Index (p = 0.04) for the in-clinic group. Both
      groups showed differences in all outcome measures over time, except for fall
      frequency. Cost comparison yielded between-group differences in treatment and
      equipment costs. Conclusions: VR is a feasible alternative to in-clinic SIBT for
      reducing postural instability in PD patients having a caregiver.

PMID- 29333457
TI  - Heterologous Secretory Expression and Characterization of Dimerized Bone
      Morphogenetic Protein 2 in Bacillus subtilis.
AB  - Recombinant human Bone Morphogenetic Protein 2 (rhBMP2) has important
      applications in the spine fusion and ortho/maxillofacial surgeries. Here we first
      report the secretory expression of biological active dimerized rhBMP2 from
      Bacillus subtilis system. The mature domain of BMP2 gene was amplified from
      pTz57R/BMP2 plasmid. By using pHT43 expression vector two constructs, pHT43-BMP2
      M (single BMP2 gene) and pHT43-BMP2-D (two BMP2 genes coupled with a linker to
      produce a dimer), were designed. After primary cloning (DH5alpha strain) and
      sequence analysis, constructs were transformed into Bacillus subtilis for
      secretory expression. Expression conditions like media (2xYT) and temperature (30
      degrees C) were optimized. Maximum 35% and 25% secretory expression of monomer
      (~13 kDa) and dimer (~25 kDa), respectively, were observed on SDS-PAGE in SCK6
      strain. The expression and dimeric nature of rhBMP2 were confirmed by western
      blot and native PAGE analysis. For rhBMP2 purification, 200 ml culture
      supernatant was freeze dried to 10 ml and dialyzed (Tris-Cl, pH 8.5) and Fast
      Protein Liquid Chromatography (6 ml, Resource Q column) was performed. The rhBMP2
      monomer and dimer were eluted at 0.9 M and 0.6 M NaCl, respectively. The alkaline
      phosphatase assay of rhBMP2 (0, 50, 100, 200, and 400 ng/ml) was analyzed on
      C2C12 cells and maximum 200 ng/ml activity was observed in dose dependent manner.

PMID- 29333456
TI  - Protective Effects of Garlic-Derived S-Allylmercaptocysteine on IL-1beta
      Stimulated Chondrocytes by Regulation of MMPs/TIMP-1 Ratio and Type II Collagen
      Expression via Suppression of NF-kappaB Pathway.
AB  - Background: Garlic-derived S-allylmercaptocysteine (SAMC) has widely been used in
      many disease therapies. However, the potential effects and mechanism of SAMC on
      IL-1beta-stimulated chondrocytes are unclear. Methods: Chondrocytes were
      isolated, and 5 ng/mL of IL-1beta was added to mimic the in vitro osteoarthritis
      (OA) model. SAMC (20 and 60 MUM) was used for the treatment in OA model. Cell
      viability was assessed by MTT method. Western blotting, Quantitative RT-PCR, and
      ELISA were performed to evaluate the mechanisms in SAMC treated OA model.
      Results: Following 48 h of IL-1beta exposure, SAMC exhibited protection effect on
      IL-1beta-injured chondrocyte viability. Type II collagen was elevated with
      reduced degradation products, as a consequence of altered MMPs/TIMP-1 ratio after
      SAMC treatment in IL-1beta-treated chondrocytes. The protein and mRNA level of
      TNF-alpha in cellular supernatant and cells were downregulated in a dose
      dependent manner. Besides, IkappaBalpha in cytoplasmic fraction was increased,
      while p65 level in nuclear fraction was decreased after SAMC treatment in OA.
      Conclusions: This study showed that SAMC may play a protective role in IL-1beta
      induced osteoarthritis (OA) model. This effect may be through inhibiting the NF
      kappaB signaling pathway, therefore altering the MMPs/TIMP-1 ratio change which
      induced type II collagen destruction and decreasing inflammatory cytokine
      secretion such as TNF-alpha.

PMID- 29333459
TI  - Assessment of Insulin Injection Practice among Diabetes Patients in a Tertiary
      Healthcare Centre in Nepal: A Preliminary Study.
AB  - Introduction: Proper insulin injection practice is essential for better diabetic
      control. This study aims to assess the insulin injection practice of patients
      with diabetes. Materials and Methods: A cross-sectional study was conducted at
      Chitwan Medical College Teaching Hospital, Bharatpur, Nepal, from February 2017
      to May 2017. Patients injecting insulin through insulin pens (n = 43) for a
      minimum of 4 weeks were consecutively recruited. Patients' baseline
      characteristics, current insulin injection technique, insulin transportation
      practice, complications of insulin injection, disposal practice of used needle,
      and acceptability of insulin were recorded. Descriptive statistics were performed
      using IBM-SPSS 20.0. Results: The insulin injection technique of patients and
      their relatives was inadequate. The majority of patients and their relatives (25,
      58.1%) mentioned that they transport their insulin cartridge without maintaining
      cold chain. Thirteen patients (30.2%, n = 43) reported complications of insulin
      injection and the most common complication among those patients was bruising (10,
      76.9%, n = 13). Almost all patients disposed the used needle improperly, and the
      common method was disposing the needle in a dustbin and then transferring to
      municipal waste disposal vehicle. Insulin was accepted by just 16 (37.2%)
      patients. Conclusion: There was a significant gap between the insulin delivery
      recommendation through insulin pen and current insulin injection practice.

PMID- 29333458
TI  - SOX6 Downregulation Induces gamma-Globin in Human beta-Thalassemia Major
      Erythroid Cells.
AB  - Background: Fetal hemoglobin (HbF; alpha2gamma2) is a potent genetic modifier of
      the severity of beta-thalassemia and sickle cell anemia. Differences in the
      levels of HbF that persist into adulthood affect the severity of sickle cell
      disease and the beta-thalassemia syndromes. Sry type HMG box (SOX6) is a potent
      silencer of HbF. Here, we reactivated gamma-globin expression by downregulating
      SOX6 to alleviate anemia in the beta-thalassemia patients. Methods: SOX6 was
      downregulated by lentiviral RNAi (RNA interference) in K562 cell line and an in
      vitro culture model of human erythropoiesis in which erythroblasts are derived
      from the normal donor mononuclear cells (MNC) or beta-thalassemia major MNC. The
      expression of gamma-globin was analyzed by qPCR (quantitative real-time PCR) and
      WB (western blot). Results: Our data showed that downregulation of SOX6 induces
      gamma-globin production in K562 cell line and human erythrocytes from normal
      donors and beta-thalassemia major donors, without altering erythroid maturation.
      Conclusions: This is the first report on gamma-globin induction by downregulation
      of SOX6 in human erythroblasts derived from beta-thalassemia major.

PMID- 29333461
TI  - Extracorporeal Shock Wave Therapy for Coronary Artery Disease: Relationship of
      Symptom Amelioration and Ischemia Improvement.
AB  - Objectives: The current management of coronary artery disease (CAD) relies on
      three major therapeutic options, namely medication, percutaneous coronary
      intervention (PCI), and coronary artery bypass grafting (CABG). However, severe
      CAD that is not indicated for PCI or CABG still bears a poor prognosis due to the
      lack of effective treatments. In 2006, extracorporeal cardiac shock wave (SW)
      therapy reported on human for the first time. This treatment resulted in better
      myocardial perfusion as evaluated by dipyridamole stress thallium scintigraphy,
      angina symptoms, and exercise tolerance. The aim of the present study was to
      investigate: myocardial perfusion images and evaluate the relationship between
      the ischemia improvement and symptom amelioration by SW therapy. Methods: We
      treated ten patients (i.e., nine males and one female) with cardiac SW therapy
      who had CAD but not indicated for PCI or CABG and aged 63-89 years old. After the
      SW therapy, all patients were followed up for three months to evaluate any
      amelioration of the myocardial ischemia based on symptoms, adenosine stress
      thallium scintigraphy, transthoracic echocardiography, and blood biochemical
      examinations. Results: The changes in various parameters were evaluated before
      and after cardiac SW therapy. The cardiac SW therapy resulted in a significant
      improvement in the symptoms as evaluated by the Canadian Cardiovascular Society
      [CCS] class score (P=0.016) and a tendency to improve in summed stress score
      (SSS) (P=0.068). However, no significant improvement was observed in the summed
      rest score (SRS), summed difference score (SDS), left ventricular wall motion
      score index (LVWMSI), N-terminal pro-brain natriuretic, and troponin I. The
      difference of CCS class score (DeltaCCS) was significantly correlated with those
      of SSS (DeltaSSS) and SDS (DeltaSDS) (r=0.69, P=0.028 and r=0.70, P=0.025,
      respectively). There was no significant correlation between DeltaCCS and other
      parameters. Furthermore, no significant difference was observed between the CCS
      improved and non-improved groups in terms of the baseline characteristics.
      Conclusion: The current study demonstrated the potential efficacy and safety of
      Cardiac SW therapy in CAD patients. As the findings indicated, symptom
      amelioration was associated with ischemia improvement by extracorporeal shock
      wave therapy for the CAD patients.

PMID- 29333462
TI  - Assessment of Ultrasound / Radio-guided Occult Lesion Localization in Non
      palpable Breast Lesions.
AB  - Objectives: Controversy exists about the localization of non-palpable breast
      lesions. In many countries, the gold standard for the diagnosis of these lesions
      is needle localization due to its accuracy. This study sought to compare the
      ultrasound- and radio-guided occult lesion localization (ROLL) as a simple method
      with the conventional procedures in terms of their diagnostic power. Methods:
      This study was conducted on 94 patients with non-palpable breast lesions detected
      by ultrasonography and localized by the combination of ultrasonography and using
      radiopharmaceuticals. One to ten hours prior to surgery, 0.1-0.2 ml (equivalent
      to 0.5-1 mCi) of Tc-99m-phytate was injected to the lesion under the guidance of
      ultrasonography. Then, the lesion was localized using a hand-held gamma probe,
      and excision of the lesion was performed according to its radioactivity signal.
      Data analysis was performed using SPSS, version 16. Results: Benign and malignant
      pathologic results were observed in 77 (81.9%) and 17(18.1%) of the patients,
      respectively, and the mean volume of the excised tissue was 26.29+/-27 mm3. 79
      patients had a solitary lesion (84%), 55 in the left breast (58.5%) and 39 in
      superolateral quadrant (41.5%). The mean size of the lesions was 15.7 mm in
      diameter (ranging from 4 to 34 mm). Additionally, there was a need to secondary
      surgery in 3 (3.2%) patients and inappropriate localization in 6 (6.4%) patients
      (subcutaneous or intra-ductal spread of radiodrug). Conclusion: Combination of
      ultrasound- and radio-guided localization methods for localizing non-palpable
      breast lesions is a simple and acceptable method for localization with no
      significant complications. For radio-drug spread and subsequent excessive excised
      tissue volume, subcutaneous and intra-ductal lesions are not suitable indication
      for ROLL.

PMID- 29333460
TI  - HLA Association with Drug-Induced Adverse Reactions.
AB  - Adverse drug reactions (ADRs) remain a common and major problem in healthcare.
      Severe cutaneous adverse drug reactions (SCARs), such as Stevens-Johnson syndrome
      (SJS)/toxic epidermal necrolysis (TEN) with mortality rate ranges from 10% to
      more than 30%, can be life threatening. A number of recent studies demonstrated
      that ADRs possess strong genetic predisposition. ADRs induced by several drugs
      have been shown to have significant associations with specific alleles of human
      leukocyte antigen (HLA) genes. For example, hypersensitivity to abacavir, a drug
      used for treating of human immunodeficiency virus (HIV) infection, has been
      proposed to be associated with allele 57:01 of HLA-B gene (terms HLA-B*57:01).
      The incidences of abacavir hypersensitivity are much higher in Caucasians
      compared to other populations due to various allele frequencies in different
      ethnic populations. The antithyroid drug- (ATDs- ) induced agranulocytosis are
      strongly associated with two alleles: HLA-B*38:02 and HLA-DRB1*08:03. In
      addition, HLA-B*15:02 allele was reported to be related to carbamazepine-induced
      SJS/TEN, and HLA-B*57:01 in abacavir hypersensitivity and flucloxacillin induced
      drug-induced liver injury (DILI). In this review, we summarized the alleles of
      HLA genes which have been proposed to have association with ADRs caused by
      different drugs.

PMID- 29333463
TI  - Characteristics of Smoothing Filters to Achieve the Guideline Recommended
      Positron Emission Tomography Image without Harmonization.
AB  - Objectives: The aim of this study is to examine the effect of different smoothing
      filters on the image quality and SUVmax to achieve the guideline recommended
      positron emission tomography (PET) image without harmonization. Methods: We used
      a Biograph mCT PET scanner. A National Electrical Manufacturers Association
      (NEMA) the International Electrotechnical Commission (IEC) body phantom was
      filled with 18F solution with a background activity of 2.65 kBq/mL and a sphere
      to-background ratio of 4. PET images obtained with the Biograph mCT PET scanner
      were reconstructed using the ordered subsets-expectation maximization (OSEM)
      algorithm with time-of-flight (TOF) models (iteration, 2; subset, 21); smoothing
      filters including the Gaussian, Butterworth, Hamming, Hann, Parzen, and Shepp
      Logan filters with various full width at half maximum (FWHM) values (1-15 mm)
      were applied. The image quality was physically assessed according to the percent
      contrast (QH,10), background variability (N10), standardized uptake value (SUV),
      and recovery coefficient (RC). The results were compared with the guideline
      recommended range proposed by the Japanese Society of Nuclear Medicine and the
      Japanese Society of Nuclear Medicine Technology. The PET digital phantom was
      developed from the digital reference object (DRO) of the NEMA IEC body phantom
      smoothed using a Gaussian filter with a 10-mm FWHM and defined as the reference
      image. The difference in the SUV between the PET image and the reference image
      was evaluated according to the root mean squared error (RMSE). Results: The FWHMs
      of the Gaussian, Butterworth, Hamming, Hann, Parzen, and Shepp-Logan filters that
      satisfied the image quality of the FDG-PET/CT standardization guideline criteria
      were 8-12 mm, 9-11 mm, 9-13 mm, 10-13 mm, 9-11 mm, and 12-15 mm, respectively.
      The FWHMs of the Gaussian, Butterworth, Hamming, Hann, Parzen, and Shepp-Logan
      filters that provided the smallest RMSE between the PET images and the 3D digital
      phantom were 7 mm, 8 mm, 8 mm, 8 mm, 7 mm, and 11 mm, respectively. Conclusion:
      The suitable FWHM for image quality or SUVmax depends on the type of smoothing
      filter that is applied.

PMID- 29333464
TI  - Comparison of TOF-PET and Bremsstrahlung SPECT Images of Yttrium-90: A Monte
      Carlo Simulation Study.
AB  - Objectives: Yttrium-90 (90Y) is a beta particle nuclide used in targeted
      radionuclide therapy which is available to both single-photon emission computed
      tomography (SPECT) and time-of-flight (TOF) positron emission tomography (PET)
      imaging. The purpose of this study was to assess the image quality of PET and
      Bremsstrahlung SPECT by simulating PET and SPECT images of 90Y using Monte Carlo
      simulation codes under the same conditions and to compare them. Methods: In-house
      Monte Carlo codes, MCEP-PET and MCEP-SPECT, were employed to simulate images. The
      phantom was a torso-shaped phantom containing six hot spheres of various sizes.
      The background concentrations of 90Y were set to 50, 100, 150, and 200 kBq/mL,
      and the concentrations of the hot spheres were 10, 20, and 40 times of those of
      the background concentrations. The acquisition time was set to 30 min, and the
      simulated sinogram data were reconstructed using the ordered subset expectation
      maximization method. The contrast recovery coefficient (CRC) and contrast-to
      noise ratio (CNR) were employed to evaluate the image qualities. Results: The CRC
      values of SPECT images were less than 40%, while those of PET images were more
      than 40% when the hot sphere was larger than 20 mm in diameter. The CNR values of
      PET images of hot spheres of diameter smaller than 20 mm were larger than those
      of SPECT images. The CNR values mostly exceeded 4, which is a criterion to
      evaluate the discernibility of hot areas. In the case of SPECT, hot spheres of
      diameter smaller than 20 mm were not discernable. On the contrary, the CNR values
      of PET images decreased to the level of SPECT, in the case of low concentration.
      Conclusion: In almost all the cases examined in this investigation, the
      quantitative indexes of TOF-PET 90Y images were better than those of
      Bremsstrahlung SPECT images. However, the superiority of PET image became
      critical in the case of low activity concentrations.

PMID- 29333465
TI  - In vivo Exposure Effects of 99mTc-methoxyisobutylisonitrile on the FDXR and XPA
      Genes Expression in Human Peripheral Blood Lymphocytes.
AB  - Objectives: In recent years, the application of radiopharmaceuticals in nuclear
      medicine has increased substantially. Following the diagnostic procedures
      performed in nuclear medicine departments, such as myocardial perfusion imaging,
      patients generally receive considerable doses of radiation. Normally, radiation
      induced DNA damages are expected following exposure to a low-dose ionizing
      radiation. In order to detect molecular changes, high-sensitivity techniques must
      be utilized. The aim of this study was to assess the effect of a low-dose (below
      10 mSv) gamma ray on gene expression using quantitative real-time polymerase
      chain reaction (qRT-PCR). Methods: Blood samples were obtained from 20 volunteer
      patients who underwent myocardial perfusion imaging. They were given various
      doses of Technetium-99m methoxyisobutylisonitrile (99mTc-MIBI). After that,
      peripheral blood mononuclear cells (PBMNs) were derived, and then total RNA was
      extracted and reverse-transcribed to cDNA. Finally, the expression levels of
      xeroderma pigmentosum complementation group-A (XPA) and ferredoxin reductase
      (FDXR) genes were determinded through qRT-PCR technique using SYBR Green.
      Results: XPA and FDXR expression levels were obtained following a very low-dose
      ionizing radiation. A significant up-regulation of both genes was observed, and
      the gene expression level of each individual patient was different. If
      differences in the administered activity and radiosensitivity are taken into
      account, the observed differences could be justified. Furthermore, gender and age
      did not play a significant role in the expression levels of the genes under
      study. Conclusion: The up-regulation of FDXR after irradiation revealed the high
      sensitivity level of this gene; therefore, it could be used as an appropriate
      biomarker for biological dosimetry. On the other hand, the up-regulation of XPA
      is an indication of DNA repair following radiation exposure. According to linear
      no-threshold model (LNT) and the results obtained from this study, a very low
      dose of ionizing radiation could bring about adverse biological effects at
      molecular level in the irradiated person.

PMID- 29333466
TI  - Evaluation of the Possible Utilization of 68Ga-DOTATOC in Diagnosis of
      Adenocarcinoma Breast Cancer.
AB  - Objectives: Studies have indicated advantageous properties of [DOTA-DPhe1, Tyr3]
      octreotide (DOTATOC) in tumor models and labeling with gallium. Breast cancer is
      the second leading cause of cancer mortality in women, and most of these cancers
      are often an adenocarcinoma. Due to the importance of target to non-target ratios
      in the efficacy of diagnosis, the pharmacokinetic of 68Ga-DOTATOC in an
      adenocarcinoma breast cancer animal model was studied in this research, and the
      optimized time for imaging was determined. Methods: 68Ga was obtained from
      68Ge/68Ga generator. The complex was prepared at optimized conditions.
      Radiochemical purity of the complex was checked using both HPLC and ITLC methods.
      Biodistribution of the complex was studied in BALB/c mice bearing adenocarcinoma
      breast cancer. Also, PET/CT imaging was performed up to 120 min post injection.
      Results: The complex was produced with radiochemical purity of greater than 98%
      and specific activity of about 40 GBq/mM at optimized conditions. Biodistribution
      of the complex was studied in BALB/c mice bearing adenocarcinoma breast cancer
      indicated fast blood clearance and significant uptake in the tumor. Significant
      tumor: blood and tumor:muscle uptake ratios were observed even at early times
      post-injection. PET/CT images were also confirmed the considerable accumulation
      of the tracer in the tumor. Conclusion: Generally, the results proved the
      possible application of the radiolabelled complex for the detection of the
      adenocarcinoma breast cancer and according to the pharmacokenitic data, the
      suitable time for imaging was determined as at least 30 min after injection.

PMID- 29333467
TI  - A Simple Non-invasive I-123-IMP Autoradiography Method Developed by Modifying the
      Simple Non-invasive I-123-IMP Microsphere Method.
AB  - Objectives: We developed a simple non-invasive I-123-N-isopropyl-p
      iodoamphetamine (123I-IMP) quantification method by analyzing chest RI
      angiography and single photon emission computed tomography (SPECT) images based
      on the microsphere model (SIMS method). Theoretically, the SIMS method could be
      changed to the simple non-invasive ARG (SIARG) method by modifying the integrated
      washout ratio (WR) to one-point WR. If the regional cerebral blood flow (rCBF)
      values derived from the SIARG and ARG methods correlate well, the facilities
      employing the ARG method can easily switch to the SIARG method. The purpose of
      this study was to develop the SIARG method by modifying the SIMS method, and to
      confirm the feasibility of this method. Methods: The correlation between the
      input counts of the SIARG method and the blood counts was determined by linear
      regression analysis. The rCBF values determined by the SIARG method were compared
      with the values obtained with the ARG and SIMS methods. Results: There was a good
      linear correlation between the SIARG counts and the arterial blood counts
      obtained by the ARG method (r=0.85, P<0.001, n=29). The rCBF values obtained by
      the ARG and SIARG methods (n=29, 696 ROIs) correlated well (y=1.01x - 3.6,
      r=0.85, P<0.001). Similarly, the rCBF values obtained by the SIARG and SIMS
      methods (n=29, 696 ROIs) correlated well (y=0.98x - 15.2, r=0.90, P<0.001). rCBF
      values obtained by the SIARG method were almost the same as the values obtained
      by the ARG method, and values of the SIMS method were 15 ml/100g/min higher that
      of those obtained by the SIARG method. Conclusion: The rCBF values obtained by
      the ARG, SIARG, and SIMS methods correlated very well. Therefore, the SIARG
      method is potentially useful for examinations in routine clinical practice.

PMID- 29333468
TI  - Extraosseous Accumulation of Technetium-99m-Methyl Diphosphonate (99mTc-MDP) in a
      Child with ALL: A Case Report.
AB  - Extraosseous accumulation of technetium-99m-methyl diphosphonate (99mTc-MDP) on
      bone scan is not common. This phenomenon is often attributed to abnormality of
      calcium metabolism and has been reported in a variety of conditions including
      metabolic diseases and malignancies. A five years old boy is presented here, who
      was admitted to the pediatric emergency suffering from fatigue, respiratory
      symptoms, weight loss, intermittent fevers, anorexia, nausea and vomiting, edema
      of legs and abdominal distension for one month. The initial laboratory analysis
      revealed hypercalcemia. The patient was referred for whole body bone scan with
      suspicion of malignancy and bone metastasis. The bone scan revealed highly
      increased radiotracer uptake in both lungs in the perfusion and blood pool
      phases. Delayed images also showed increased activity in lungs and gastric wall.
      The skeleton was not seen clearly. Bone marrow aspiration was done and
      established the diagnosis of ALL. The patient deceased due to respiratory failure
      20 days later. Diffuse lung uptake in this patient was consistent with
      respiratory failure and poor prognosis. It is reported that bone scan may be
      useful for assessment of the extent of metastatic calcification and may establish
      suitable management to prevent organ failure.

PMID- 29333469
TI  - Utility of F-18 FDG PET/CT for Detection of Bone Marrow Metastases in Prostate
      Cancer Patients Treated with Radium-223.
AB  - A 76-year-old man with symptomatic bone metastases from castration-resistant
      prostate cancer underwent Radium-223-dichloride (Ra-223) therapy. Before Ra-223
      therapy, he had normal peripheral blood cell counts. Ra-223 therapy relieved his
      shoulder and low back pain. The elevation of the serum prostate-specific antigen
      (PSA), doubling every month during Ra-223 therapy, suggested a PSA flare or
      relapse. Some lesions showed decrease and some lesions showed increase on Tc-99m
      hydroxymethylene diphosphonate bone scintigraphy at two weeks after the third
      injection of Ra-223 therapy. Ra-223 therapy was discontinued due to
      thrombocytopenia that was getting worse rapidly. After treatment discontinuation,
      namely four weeks after the third injection of Ra-223, F-18 fluorodeoxyglucose
      (FDG) Positron Emission Tomography (PET)/CT and a biopsy were performed to
      evaluate for metastases, and bone marrow metastases were found. Ra-223 was
      effective for osteoblastic lesions, but not for bone marrow metastases. FDG
      PET/CT, but not a Tc-99m based bone scan, detected diffuse bone marrow
      involvement by cancer. This case report is the first to clarify the utility of
      FDG PET for the detection of bone marrow metastases confirmed by pathological
      examination in Ra-223 therapy for progressive castration-resistant prostate
      cancer.

PMID- 29333470
TI  - History and Perspectives of Nuclear Medicine in Myanmar.
AB  - Nuclear Medicine was established in Myanmar in 1963 by Dr Soe Myint and
      International Atomic Energy expert Dr R. Hochel at Yangon General Hospital.
      Nuclear medicine diagnostic and therapeutic services started with Probe
      Scintillation Detector Systems and rectilinear scanner. In the early stage, many
      Nuclear Medicine specialists from the International Atomic Energy Agency (IAEA)
      spent some time in Myanmar and made significant contributions to the development
      of Nuclear Medicine in our country. The department participated in various IAEA
      technical cooperation projects and regional cooperation projects. By the late
      1990s, new centers were established in Mandalay, Naypyidaw, and North Okkalapa
      Teaching Hospital of University of Medicine 11, Yangon. The training program
      related to Nuclear Medicine includes a postgraduate master's degree (three years)
      at the University of Medicine. Currently, all centers are equipped with SPECT,
      SPECT-CT, PET-CT, and cyclotron in Yangon General Hospital. Up until now, the
      International Atomic Energy Agency has been playing a crucial role in the growth
      and development of Nuclear Medicine in Myanmar. Our vision is to provide a wide
      spectrum of nuclear medicine services at a level compatible with the
      international standards to become a Center of Excellence.

PMID- 29333471
TI  - Sectional Anatomy Quiz II.
AB  - This mage-based series comprises of a quiz pertaining to the identification of
      salient and important anatomical structures and landmarks expected to be seen at
      a given level on the computed tomography (CT). The representative image is
      followed by a series of images showing the examples of different commonly
      encountered pathological entities that can be seen at this level in a routine
      clinical practice. Readers are encouraged to identify the highlighted anatomical
      structures and landmarks in all the images and appreciate the alterations in the
      appearance of the normal structures resulting from the presence of a pathology.
      It is expected that this series will assist in improving the confidence of the
      nuclear physicians in the interpretation of the CT component of the single photon
      emission computed tomography (SPECT) and positron emission tomography (PET)
      studies.

PMID- 29333472
TI  - Black-White Disparities in Breast Cancer Subtype: The Intersection of Socially
      Patterned Stress and Genetic Expression.
AB  - Hormone receptor negative (HR-) breast cancer subtypes are etiologically distinct
      from the more common, less aggressive, and more treatable form of estrogen
      receptor positive (ER+) breast cancer. Numerous population-based studies have
      found that, in the United States, Black women are 2 to 3 times more likely to
      develop HR- breast cancer than White women. Much of the existing research on
      racial disparities in breast cancer subtype has focused on identifying
      predisposing genetic factors associated with African ancestry. This approach
      fails to acknowledge that racial stratification shapes a wide range of
      environmental and social exposures over the life course. Human stress genomics
      considers the role of individual stress perceptions on gene expression. Yet, the
      role of structurally rooted biopsychosocial processes that may be activated by
      the social patterning of stressors in an historically unequal society, whether
      perceived by individual black women or not, could also impact cellular physiology
      and gene expression patterns relevant to HR- breast cancer etiology. Using the
      weathering hypothesis as our conceptual framework, we develop a structural
      perspective for examining racial disparities in breast cancer subtypes,
      integrating important findings from the stress biology, breast cancer
      epidemiology, and health disparities literatures. After integrating key findings
      from these largely independent literatures, we develop a theoretically and
      empirically guided framework for assessing potential multilevel factors relevant
      to the development of HR- breast cancer disproportionately among Black women in
      the US. We hypothesize that a dynamic interplay among socially patterned
      psychosocial stressors, physiological & behavioral responses, and genomic
      pathways contribute to the increased risk of HR- breast cancer among Black women.
      This work provides a basis for exploring potential alternative pathways linking
      the lived experience of race to the risk of HR- breast cancer, and suggests new
      avenues for research and public health action.

PMID- 29333474
TI  - Saccades in progressive supranuclear palsy - maladapted, irregular, curved, and
      slow.
AB  - Background and objectives: Slowed and curved rapid eye movements, saccades, are
      the well-known features of progressive supranuclear palsy (PSP). We hypothesized
      that the saccades in PSP are not only slow and curved, but they are also
      irregular and have timing deficits. Methods: We tested this hypothesis in 12
      patients with PSP by measuring vertical and horizontal visually guided saccades
      using a limbus tracker. Results: Both, horizontal and vertical saccades were slow
      and had irregular trajectory and velocity profiles, but deficits were much more
      robust in vertical saccades. The irregularity in the saccade velocity was due to
      premature interruptions that either completely stopped the eyes, or moved the
      eyes at much slower velocity along or in the opposite direction of the ongoing
      saccade. The direction of the eyes' trajectory was often changed after the
      interruption. We simulated a conductance based single-compartment model of the
      burst neurons embedded in local feedback circuit for saccade generation. This
      model mimicked anatomical and physiological realism, while allowing the liberty
      to selectively change the activation of individual burst neurons or the pause
      neurons. The PSP saccades were comparable to the simulations during reduced
      activity of the inhibitory and excitatory burst neurons. Conclusion: PSP saccades
      are due to the paucity in burst generation at the excitatory and imprecise timing
      signal from the inhibitory burst neurons. Premature discharge of the inhibitory
      burst neuron further leads to breaks in the saccade trajectory, and maladaptive
      superior colliculus activity leading to aberrant saccades changing the intended
      trajectory of the ongoing saccade.

PMID- 29333475
TI  - Whole-mount Enteroid Proliferation Staining.
AB  - Small intestinal organoids, otherwise known as enteroids, have become an
      increasingly utilized model for intestinal biology in vitro as they recapitulate
      the various epithelial cells within the intestinal crypt (Mahe et al., 2013; Sato
      et al., 2009). Assessment of growth dynamics within these cultures is an
      important step to understanding how alterations in gene expression, treatment
      with protective and toxic agents, and genetic mutations alter properties
      essential for crypt growth and survival as well as the stem cell properties of
      the individual cells within the crypt. This protocol describes a method of
      visualization of proliferating cells within the crypt in three dimensions
      (Barrett et al., 2015). Whole-mount proliferation staining of enteroids using EdU
      incorporation enables the researcher to view all proliferating cells within the
      enteroid as opposed to obtaining growth information in thin slices as would be
      seen with embedding and sectioning, ensuring a true representation of
      proliferation from the stem cell compartment to the terminally differentiated
      cells of the crypt.

PMID- 29333476
TI  - In vitro Flow Adhesion Assay for Analyzing Shear-resistant Adhesion of Metastatic
      Cancer Cells to Endothelial Cells.
AB  - Hematogenous metastasis is a primary cause of mortality from metastatic cancer.
      The shear-resistant adhesion of circulating tumor cells to the vascular
      endothelial cell surface under blood flow is an essential step in cell
      extravasation and further tissue invasion. This is similar to a process exploited
      by leukocytes for adhesion to inflamed blood vessels (leukocyte mimicry). The
      shear resistant adhesion is mediated by high affinity interactions between
      endothelial adhesion molecules and their counter receptor ligand expressed on
      circulating cells. Thus, weak interaction results in a rapid detachment of
      circulating cells from endothelium. Despite the critical role of vascular
      adhesion of cancer cells in hematogenous metastasis, our knowledge regarding this
      process has been limited due to the difficulty of mimicking dynamic flow
      conditions in vitro. In order to gain better insight into the shear-resistant
      adhesion of cancer cells to the endothelium, we developed a protocol for
      measuring the shear resistant adhesion of circulating tumor cells to endothelial
      cells under physiologic flow conditions by adapting a well established flow
      adhesion assay for inflammatory cells. This technique is useful to evaluate 1)
      the shear resistant adhesion competency of cancer cells and 2) the endothelial
      adhesion molecules necessary to support cancer cell adhesion (Kang et al., 2015).

PMID- 29333477
TI  - Notch Ligand Binding Assay Using Flow Cytometry.
AB  - Notch signaling is an evolutionary conserved signaling pathway that plays an
      indispensable role during development, and in the maintenance of homeostatic
      processes, in a wide variety of tissues (Kopan, 2012; Hori et al., 2013). The
      multifaceted roles of Notch signaling are stringently regulated at different
      levels. One of the most important aspects of regulation is the binding of
      different Notch ligands to each Notch receptor (NOTCH1-NOTCH4). Canonical ligands
      Delta or Serrate (in Drosophila), and Delta-like (DLL1 and DLL4) or Jagged (JAG1
      and JAG2) (in mammals), are transmembrane glycoproteins. Ligands expressed on one
      cell bind to Notch receptors on an adjacent cell to induce Notch signaling.
      Glycosylation of Notch receptor extracellular domain by O-fucose and O-GlcNAc
      glycans is well established as critical regulators for Notch signaling strength
      (Stanley and Okajima, 2010; Haltom and Jafar-Nejad, 2015; Sawaguchi et al.,
      2017). In order to characterize Notch ligand binding to Notch receptors in
      isolated cells, we utilize Notch ligand extracellular domains tagged at the C
      terminus by a human Fc domain, and determine binding of fluorescent anti-Fc
      antibody by flow cytometry.

PMID- 29333473
TI  - Charge migration and charge transfer in molecular systems.
AB  - The transfer of charge at the molecular level plays a fundamental role in many
      areas of chemistry, physics, biology and materials science. Today, more than 60
      years after the seminal work of R. A. Marcus, charge transfer is still a very
      active field of research. An important recent impetus comes from the ability to
      resolve ever faster temporal events, down to the attosecond time scale. Such a
      high temporal resolution now offers the possibility to unravel the most
      elementary quantum dynamics of both electrons and nuclei that participate in the
      complex process of charge transfer. This review covers recent research that
      addresses the following questions. Can we reconstruct the migration of charge
      across a molecule on the atomic length and electronic time scales? Can we use
      strong laser fields to control charge migration? Can we temporally resolve and
      understand intramolecular charge transfer in dissociative ionization of small
      molecules, in transition-metal complexes and in conjugated polymers? Can we
      tailor molecular systems towards specific charge-transfer processes? What are the
      time scales of the elementary steps of charge transfer in liquids and
      nanoparticles? Important new insights into each of these topics, obtained from
      state-of-the-art ultrafast spectroscopy and/or theoretical methods, are
      summarized in this review.

PMID- 29333478
TI  - A General Method for Intracellular Protein Delivery through 'E-tag' Protein
      Engineering and Arginine Functionalized Gold Nanoparticles.
AB  - In this protocol, we describe a method for direct cytosolic protein delivery that
      avoids endosomal entrapment of the delivered proteins. We achieved this by
      tagging the desired protein with an oligo glutamic acid tag (E-tag), and
      subsequently using carrier gold nanoparticles to deliver these E-tagged proteins.
      When E-tagged proteins and nanoparticles were mixed, they formed nanoassemblies,
      which got fused to cell membrane upon incubation and directly released the E
      tagged protein into cell cytosol. We used this method to deliver a wide variety
      of proteins with different sizes, charges, and functions in various cell lines
      (Mout et al., 2017). To use this protocol, the first step is to generate the
      required materials (gold nanoparticles, recombinant E-tagged proteins).
      Laboratory-synthesis of gold nanoparticles has been previously described (Yang et
      al., 2011). Desired E-tagged proteins can be cloned from the corresponding genes,
      and expressed and purified using standard laboratory procedures. We will use E
      tagged green fluorescent protein (GFP) as a reference protein here. Users can
      simply insert an E-tag into their protein of interest, at either terminus. To
      achieve maximum delivery efficiency, we suggest users testing different length of
      E-tags. For example, we inserted E = 0 to 20 (E0 means no E-tag insertion, and
      E20 means 20 glutamic acids insertion in a row) to most of the proteins we
      tested, and screened for optimal E-tagged length for highest delivery efficiency.
      E10-tagged proteins gave us the highest delivery efficiency for most of the
      proteins (except for Cas9, where E20 tag showed highest delivery efficiency).
      Once these materials are ready, it takes about ~10 min to make the E-tagged
      protein and nanoparticle nanoassemblies, which are immediately used for delivery.
      Complete delivery (~100% for GFP-E10) is achieved in less than 3 h.

PMID- 29333479
TI  - Oral Microbiome Characterization in Murine Models.
AB  - The oral microbiome has been implicated as a trigger for immune responsiveness in
      the oral cavity, particularly in the setting of the inflammatory disease
      periodontitis. The protocol presented here is aimed at characterizing the oral
      microbiome in murine models at steady state and during perturbations of immunity
      or physiology. Herein, we describe murine oral microbiome sampling procedures,
      processing of low biomass samples and subsequent microbiome characterization
      based on 16S rRNA gene sequencing.

PMID- 29333480
TI  - GPU-based Branchless Distance-Driven Projection and Backprojection.
AB  - Projection and backprojection operations are essential in a variety of image
      reconstruction and physical correction algorithms in CT. The distance-driven (DD)
      projection and backprojection are widely used for their highly sequential memory
      access pattern and low arithmetic cost. However, a typical DD implementation has
      an inner loop that adjusts the calculation depending on the relative position
      between voxel and detector cell boundaries. The irregularity of the branch
      behavior makes it inefficient to be implemented on massively parallel computing
      devices such as graphics processing units (GPUs). Such irregular branch behaviors
      can be eliminated by factorizing the DD operation as three branchless steps:
      integration, linear interpolation, and differentiation, all of which are highly
      amenable to massive vectorization. In this paper, we implement and evaluate a
      highly parallel branchless DD algorithm for 3D cone beam CT. The algorithm
      utilizes the texture memory and hardware interpolation on GPUs to achieve fast
      computational speed. The developed branchless DD algorithm achieved 137-fold
      speedup for forward projection and 188-fold speedup for backprojection relative
      to a single-thread CPU implementation. Compared with a state-of-the-art 32-thread
      CPU implementation, the proposed branchless DD achieved 8-fold acceleration for
      forward projection and 10-fold acceleration for backprojection. GPU based
      branchless DD method was evaluated by iterative reconstruction algorithms with
      both simulation and real datasets. It obtained visually identical images as the
      CPU reference algorithm.

PMID- 29333481
TI  - Theta sequences of grid cell populations can provide a movement-direction signal.
AB  - It has been proposed that path integration in mammals is performed by the
      convergence of internally generated speed and directional inputs onto grid cells.
      Although this hypothesis has been supported by the discovery that head direction,
      speed, and grid cells are intermixed within entorhinal cortex and by the recent
      finding that head-direction inputs are necessary for grid firing, many details on
      how grid cells are generated have remained elusive. For example, analysis of
      recording data suggests that substituting head direction for movement direction
      accrues errors that preclude the formation of grid patterns. To address this
      discrepancy, we propose that the organization of grid networks makes it plausible
      that movement-direction signals are an output from grid cells and that temporally
      precise grid cell sequences provide a robust directional signal to other spatial
      and directional cell types.

PMID- 29333482
TI  - Flexibility in the face of fear: Hippocampal-prefrontal regulation of fear and
      avoidance.
AB  - Generating appropriate defensive behaviors in the face of threat is essential to
      survival. Although many of these behaviors are 'hard-wired', they are also
      flexible. For example, Pavlovian fear conditioning generates learned defensive
      responses, such as conditioned freezing, that can be suppressed through
      extinction. The expression of extinguished responses is highly context-dependent,
      allowing animals to engage behavioral responses appropriate to the contexts in
      which threats are encountered. Likewise, animals and humans will avoid noxious
      outcomes if given the opportunity. In instrumental avoidance learning, for
      example, animals overcome conditioned defensive responses, including freezing, in
      order to actively avoid aversive stimuli. Recent work has greatly advanced
      understanding of the neural basis of these phenomena and has revealed common
      circuits involved in the regulation of fear. Specifically, the hippocampus and
      medial prefrontal cortex play pivotal roles in gating fear reactions and
      instrumental actions, mediated by the amygdala and nucleus accumbens,
      respectively. Because an inability to adaptively regulate fear and defensive
      behavior is a central component of many anxiety disorders, the brain circuits
      that promote flexible responses to threat are of great clinical significance.

PMID- 29333483
TI  - How heart rate variability affects emotion regulation brain networks.
AB  - Individuals with high heart rate variability tend to have better emotional well
      being than those with low heart rate variability, but the mechanisms of this
      association are not yet clear. In this paper, we propose the novel hypothesis
      that by inducing oscillatory activity in the brain, high amplitude oscillations
      in heart rate enhance functional connectivity in brain networks associated with
      emotion regulation. Recent studies using daily biofeedback sessions to increase
      the amplitude of heart rate oscillations suggest that high amplitude
      physiological oscillations have a causal impact on emotional well-being. Because
      blood flow timing helps determine brain network structure and function, slow
      oscillations in heart rate have the potential to strengthen brain network
      dynamics, especially in medial prefrontal regulatory regions that are
      particularly sensitive to physiological oscillations.

PMID- 29333485
TI  - Study of Incidence of Gross Urogenital Lesions and Abnormalities on Does
      Slaughtered at Nyagatare Slaughterhouse, Eastern Province, Rwanda.
AB  - Reproductive and urinary tract abnormalities are a cause of infertility,
      reproductive inefficiency, and economic losses in goats. The aim of this study
      was to investigate the occurrence and nature of reproductive and urinary tract
      abnormalities encountered in female goats slaughtered at Nyagatare abattoir in
      the Eastern Province of Rwanda. Reproductive and urinary organs from 369 female
      goat carcasses were opened by incision and then given a thorough macroscopic
      examination by visually inspecting and palpating for evidence of abnormalities.
      The results showed that there was an overall occurrence of 7.8% reproductive
      organ/tract abnormalities and 10.6% urinary organ/tract abnormalities. Ovarian
      hypoplasia was the reproductive abnormality with the highest overall occurrence
      (32.3%) and renal calculi were the urinary organ abnormality with the highest
      occurrence (38.1%). 95.2% of the reproductive organ/tract abnormalities observed
      usually result in infertility and 91.3% of the urinary organ/tract abnormalities
      observed result in economic losses through condemnation of kidneys at slaughter.
      The high incidence of the observed urinary organ/tract abnormalities represents a
      potential public health challenge. There was no significant difference in the
      occurrence of reproductive organ/tract abnormalities according to breed (p >
      0.05, n = 31). There was also no significant difference in the occurrence of
      urinary organ abnormalities according to breed (p > 0.05, n = 42).

PMID- 29333486
TI  - Ethical Considerations When Delivering Behavior Analytic Services for Problem
      Behavior via Telehealth.
AB  - Delivery of healthcare services via telehealth has been growing in popularity,
      and work completed by behavior analytic researchers and practitioners have
      supported this trend. Behavior analysts at the University of Iowa Children's
      Hospital (UICH) developed a telehealth model of service delivery to build upon
      their already established in-clinic and in-home services. Results from their
      telehealth studies showed positive effects. Social functions were identified for
      most children, and problem behavior decreased by an average of 94.14%.
      Additionally, parent satisfaction was quite high, suggesting this mode of service
      delivery was acceptable to caregivers. Given the increasing empirical support for
      providing behavior analytic services via telehealth, careful consideration needs
      to be given to the numerous ethical issues involved in telehealth service
      delivery. The current article describes the telehealth service delivery model
      developed at UICH as well as the ethical issues considered at different points
      when delivering these telehealth services. Following these ethical
      considerations, implications for future research and clinical practice are
      discussed.

PMID- 29333484
TI  - Approaching the third decade of paediatric palliative oncology investigation:
      historical progress and future directions.
AB  - Paediatric palliative care (PPC) endeavours to alleviate the suffering and
      improve the quality of life of children with serious illnesses and their
      families. In the past two decades since WHO defined PPC and called for its
      inclusion in paediatric oncology care, rigorous investigation has provided
      important insights. For example, the first decade of research focused on end-of
      life experiences of the child and the family, underscoring the high prevalence of
      symptom burden, the barriers to parent-provider concordance with regards to
      prognosis, as well as the need for bereavement supports. The second decade
      expanded PPC oncology investigation to include the entire cancer continuum and
      the voices of patients. Other studies identified the need for support of parents,
      siblings, and racial and ethnic minority groups. Promising interventions designed
      to improve outcomes were tested in randomised clinical trials. Future research
      will build on these findings and pose novel questions about how to continue to
      reduce the burdens of paediatric cancer.

PMID- 29333487
TI  - Activation of the Medial Prefrontal Cortex Reverses Cognitive and Respiratory
      Symptoms in a Mouse Model of Rett Syndrome.
AB  - Rett syndrome (RTT) is a severe neurodevelopmental disorder caused by loss-of
      function mutations in the gene encoding methyl-CpG-binding protein 2 (MeCP2; Amir
      et al., 1999), a transcriptional regulatory protein (Klose et al., 2005). Mouse
      models of RTT (Mecp2 mutants) exhibit excitatory hypoconnectivity in the medial
      prefrontal cortex (mPFC; Sceniak et al., 2015), a region critical for functions
      that are abnormal in RTT patients, ranging from learning and memory to regulation
      of visceral homeostasis (Riga et al., 2014). The present study was designed to
      test the hypothesis that increasing the activity of mPFC pyramidal neurons in
      heterozygous female Mecp2 mutants (Hets) would ameliorate RTT-like symptoms,
      including deficits in respiratory control and long-term retrieval of auditory
      conditioned fear. Selective activation of mPFC pyramidal neurons in adult animals
      was achieved by bilateral infection with an AAV8 vector expressing excitatory
      hm3D(Gq) DREADD (Designer Receptors Exclusively Activated by Designer Drugs)
      (Armbruster et al., 2007) under the control of the CamKIIa promoter. DREADD
      activation in Mecp2 Hets completely restored long-term retrieval of auditory
      conditioned fear, eliminated respiratory apneas, and reduced respiratory
      frequency variability to wild-type (Wt) levels. Reversal of respiratory symptoms
      following mPFC activation was associated with normalization of Fos protein
      levels, a marker of neuronal activity, in a subset of brainstem respiratory
      neurons. Thus, despite reduced levels of MeCP2 and severe neurological deficits,
      mPFC circuits in Het mice are sufficiently intact to generate normal behavioral
      output when pyramidal cell activity is increased. These findings highlight the
      contribution of mPFC hypofunction to the pathophysiology of RTT and raise the
      possibility that selective activation of cortical regions such as the mPFC could
      provide therapeutic benefit to RTT patients.

PMID- 29333488
TI  - Dopamine Development in the Mouse Orbital Prefrontal Cortex Is Protracted and
      Sensitive to Amphetamine in Adolescence.
AB  - The prefrontal cortex (PFC) is divided into subregions, including the medial and
      orbital prefrontal cortices. Dopamine connectivity in the medial PFC (mPFC)
      continues to be established throughout adolescence as the result of the
      continuous growth of axons that innervated the nucleus accumbens (NAcc) prior to
      adolescence. During this period, dopamine axons remain vulnerable to
      environmental influences, such as drugs used recreationally by humans. The
      developmental trajectory of the orbital prefrontal dopamine innervation remains
      almost completely unstudied. Nonetheless, the orbital PFC (oPFC) is critical for
      some of the most complex functions of the PFC and is disrupted by drugs of abuse,
      both in adolescent humans and rodents. Here, we use quantitative neuroanatomy,
      axon-initiated viral-vector recombination, and pharmacology in mice to determine
      the spatiotemporal development of the dopamine innervation to the oPFC and its
      vulnerability to amphetamine in adolescence. We find that dopamine innervation to
      the oPFC also continues to increase during adolescence and that this increase is
      due to the growth of new dopamine axons to this region. Furthermore, amphetamine
      in adolescence dramatically reduces the number of presynaptic sites on oPFC
      dopamine axons. In contrast, dopamine innervation to the piriform cortex is not
      protracted across adolescence and is not impacted by amphetamine exposure during
      adolescence, indicating that dopamine development during adolescence is a
      uniquely prefrontal phenomenon. This renders these fibers, and the PFC in
      general, particularly vulnerable to environmental risk factors during
      adolescence, such as recreational drug use.

PMID- 29333489
TI  - Degradable acetalated dextran microparticles for tunable release of an engineered
      hepatocyte growth factor fragment.
AB  - Injectable biomaterials are promising as new therapies to treat myocardial
      infarction (MI). One useful property of biomaterials is the ability to protect
      and sustain release of therapeutic payloads. In order to create a platform for
      optimizing the release rate of cardioprotective molecules we utilized the tunable
      degradation of acetalated dextran (AcDex). We created microparticles with three
      distinct degradation profiles and showed that the consequent protein release
      profiles could be modulated within the infarcted heart. This enabled us to
      determine how delivery rate impacted the efficacy of a model therapeutic, an
      engineered hepatocyte growth factor fragment (HGF-f). Our results showed that the
      cardioprotective efficacy of HGF-f was optimal when delivered over three days
      post-intramyocardial injection, yielding the largest arterioles, fewest apoptotic
      cardiomyocytes bordering the infarct and the smallest infarcts compared to empty
      particle treatment four weeks after injection. This work demonstrates the
      potential of using AcDex particles as a delivery platform to optimize the time
      frame for delivering therapeutic proteins to the heart.

PMID- 29333490
TI  - Inhibition of Bacterial Adhesion on Nanotextured Stainless Steel 316L by
      Electrochemical Etching.
AB  - Bacterial adhesion to stainless steel 316L (SS316L), which is an alloy typically
      used in many medical devices and food processing equipment, can cause serious
      infections along with substantial healthcare costs. This work demonstrates that
      nanotextured SS316L surfaces produced by electrochemical etching effectively
      inhibit bacterial adhesion of both Gram-negative Escherichia coli and Gram
      positive Staphylococcus aureus, but exhibit cytocompatibility and no toxicity
      toward mammalian cells in vitro. Additionally, the electrochemical surface
      modification on SS316L results in formation of superior passive layer at the
      surface, improving corrosion resistance. The nanotextured SS316L offers
      significant potential for medical applications based on the surface structure
      induced reduction of bacterial adhesion without use of antibiotic or chemical
      modifications while providing cytocompatibility and corrosion resistance in
      physiological conditions.

PMID- 29333491
TI  - Multifunctional Bioreactor System for Human Intestine Tissues.
AB  - The three-dimensional (3D) cultivation of intestinal cells and tissues in dynamic
      bioreactor systems to represent in vivo intestinal microenvironments is essential
      for developing regenerative medicine treatments for intestinal diseases. We have
      previously developed in vitro human intestinal tissue systems using a 3D porous
      silk scaffold system with intestinal architectures and topographical features for
      the adhesion, growth, and differentiation of intestinal cells under static
      culture conditions. In this study, we designed and fabricated a multifunctional
      bioreactor system that incorporates pre-epithelialized 3D silk scaffolds in a
      dynamic culture environment for in vitro engineering of human intestine tissues.
      The bioreactor system allows for control of oxygen levels in perfusion fluids
      (aerobic simulated intestinal fluid (SIF), microaerobic SIF, and anaerobic SIF),
      while ensuring control over the mechanical and chemical microenvironments present
      in native human intestines. The bioreactor system also enables 3D cell culture
      with spatial separation and cultivation of cocultured epithelial and stromal
      cells. Preliminary functional analysis of tissues housed in the bioreactor
      demonstrated that the 3D tissue constructs survived and maintained typical
      phenotypes of intestinal epithelium, including epithelial tight junction
      formation, intestinal biomarker expression, microvilli formation, and mucus
      secretion. The unique combination of a dynamic bioreactor and 3D intestinal
      constructs offers utility for engineering human intestinal tissues for the study
      of intestinal diseases and discovery options for new treatments.

PMID- 29333492
TI  - Assessment of Crystal Morphology on Uptake, Particle Dissolution, and Toxicity of
      Nanoscale Titanium Dioxide on Artemia salina.
AB  - Knowledge of nanomaterial toxicity is critical to avoid adverse effects on human
      and environment health. In this study, the influences of crystal morphology on
      physico-chemical and toxic properties of nanoscale TiO2 (n-TiO2) were
      investigated. Artemia salina were exposed to anatase, rutile and mixture
      polymorphs of n-TiO2 in seawater. Short-term (24 h) and long-term (96 h)
      exposures were conducted in 1, 10 and 100 mg/L suspensions of n-TiO2 in the
      presence and absence of food. Anatase form had highest accumulation followed by
      mixture and rutile. Presence of food greatly reduced accumulation. n-TiO2
      dissolution was not significant in seawater (p<0.05) nor was influenced from
      crystal structure. Highest toxic effects occurred in 96h exposure in the order of
      anatase > mixture > rutile. Mortality and oxidative stress levels increased with
      increasing n-TiO2 concentration and exposure time (p<0.05). Presence of food in
      the exposure medium alleviated the oxidative stress, indicating that deprivation
      from food could promote toxic effects of n-TiO2 under long-term exposure.

PMID- 29333493
TI  - A quality improvement project aimed at adapting primary care to ensure the
      delivery of evidence-based psychotherapy for adult anxiety.
AB  - Primary care patients frequently present with anxiety with prevalence ratios up
      to 30%. Brief cognitive-behavioural therapy (CBT) has been shown in meta-analytic
      studies to have a strong effect size in the treatment of anxiety. However, in
      surveys of anxious primary care patients, nearly 80% indicated that they had not
      received CBT. In 2010, a model of CBT (Coordinated Anxiety Learning and
      Management (CALM)) adapted to primary care for adult anxiety was published based
      on results of a randomised controlled trial. This project aimed to integrate an
      adaptation of CALM into one primary care practice, using results from the
      published research as a benchmark with the secondary intent to spread a
      successful model to other practices. A quality improvement approach was used to
      translate the CALM model of CBT for anxiety into one primary care clinic. Plan-Do
      Study-Act steps are highlighted as important steps towards our goal of comparing
      our outcomes with benchmarks from original research. Patients with anxiety as
      measured by a score of 10 or higher on the Generalized Anxiety Disorder 7 item
      scale (GAD-7) were offered CBT as delivered by licensed social workers with
      support by a PhD psychologist. Outcomes were tracked and entered into an
      electronic registry, which became a critical tool upon which to adapt and improve
      our delivery of psychotherapy to our patient population. Challenges and
      adaptations to the model are discussed. Our 6-month response rates on the GAD-7
      were 51%, which was comparable with that of the original research (57%). Quality
      improvement methods were critical in discovering which adaptations were needed
      before spread. Among these, embedding a process of measurement and data entry and
      ongoing feedback to patients and therapists using this data are critical step
      towards sustaining and improving the delivery of CBT in primary care.

PMID- 29333494
TI  - Ensuring adequate vascular access in patients with major trauma: a quality
      improvement initiative.
AB  - Ensuring adequate vascular access in major trauma patients prior to
      decompensative physiological processes is crucial to patient outcomes. Most
      protocols suggest achieving two 18-gauge or larger intravenous lines immediately
      in patients with major trauma. We discuss a quality improvement approach to
      ensure that >90% of patients with major trauma (as defined by an injury severity
      score >=12) at a level one trauma centre receive timely and adequate fluid
      access. Applying Donabedian principles for process improvement, we used the
      Alberta Trauma Registry to perform a 4-month chart audit on patients with major
      trauma at the University of Alberta Hospital. Background data were supported with
      a formal root cause analysis to outline the problems and generate plan, do, study
      and act (PDSA) rapid change cycles. These PDSA cycles were then implemented over
      the course of 2 months to alter system and personnel barriers to care, thereby
      ensuring that patients with major trauma received adequate vascular access for
      fluid resuscitation. This was followed by a 6-month sustainability assessment.
      The percentage of patients with major trauma who received adequate fluid access
      went from a mean of 55.5% to >90% in 2 months and was sustained at or greater
      than 90% for 6 consecutive months. The formal application of quality improvement
      processes is uncommon in trauma care but is much needed to ensure success and
      sustainability of quality initiatives. Planning including engagement and
      prechange awareness is crucial to staff engagement, change, and sustainment.
      Formal quality improvement and change management techniques can elicit rapid and
      sustainable changes in trauma care. We provide a framework for change to increase
      compliance with fluid access in patients with major trauma.

PMID- 29333495
TI  - Integrating prevention and health promotion in a London prison.
AB  - Many people enter prison with poor health from a background of deprivation and
      with unhealthy lifestyle habits, yet spending time in prisons is often actively
      detrimental to health. There is therefore a clear value in providing high-quality
      health promotion services in prisons that are effective at reaching those who
      need support to improve their lifestyle. The health promotion service at HMP
      Brixton provides a health trainers clinic to address lifestyle issues but found
      that it was sometimes challenging to identify appropriate patients and that the
      service was inefficient as a result. Analysis of our referral sources suggested
      that taking steps to increase the proportion of referrals made during screening
      and other clinics might lead to more appropriate and engaged patients. In this
      study, we set out to use quality improvement methods to increase referral from
      these sources. This involved improvements to the processes involved in delivering
      National Health Service Health Checks that were the primary source of referrals
      for health trainers and by improving links between the health trainer team and
      other clinicians. The changes were successful in increasing referrals from these
      sources. This work was completed during a period of exceptional disruption in the
      prison service and is relevant to secure healthcare sites that aim to ensure
      prevention activities are efficient and targeted.

PMID- 29333496
TI  - Improving the wait time to consultation at the emergency department.
AB  - Prolonged wait times at the emergency department (ED) are associated with
      increased morbidity and mortality, and decreased patient satisfaction. Reducing
      wait times at the ED is challenging. The objective of this study is to determine
      if the implementation of a series of interventions would help decrease the wait
      time to consultation (WTC) for patients at the ED within 6 months. Interventions
      include creation of a common board detailing work output, matching manpower to
      patient arrivals and adopting a team-based model of care. A retrospective
      analysis of the period from January 2015 to May 2016 was undertaken to define
      baseline duration for WTC. Rapid PDSA (Plan, Do, Study, Act) cycles were used to
      implement a series of interventions, and changes in wait time were tracked, with
      concurrent patient load, rostered manpower and number of admissions from ED.
      Results of the interventions were tracked from 1 October 2016 to 30 April 2017.
      There was improvement in WTC within 6 months of initiation of interventions. The
      improvements demonstrated appeared consistent and sustained. The average 95th
      centile WTC decreased by 38 min to 124 min, from the baseline duration of 162
      min. The median WTC improved to 21 min, compared with a baseline timing of 24
      min. The improvements occurred despite greater patient load of 4317 patients per
      month, compared with baseline monthly average of 4053 patients. There was no
      increase in admissions from ED and no change in the amount of ED manpower over
      the same period. We demonstrate how implementation of low-cost interventions,
      enabling transparency, equitable workload and use of a team-based care model can
      help to bring down wait times for patients. Quality improvement efforts were
      sustained by employing a data-driven approach, support from senior clinicians and
      providing constant feedback on outcomes.

PMID- 29333497
TI  - Work efficiency improvement of >90% after implementation of an annual inpatient
      blood products administration consent form.
AB  - Paediatric haematology, oncology and bone marrow transplant (BMT) patients
      frequently require transfusion of blood products. Our institution required a new
      transfusion consent be obtained every admission. The objectives of this project
      were to: revise inpatient blood products consent form to be valid for 1 year,
      decrease provider time spent consenting from 15 to <5 min per admission, and
      improve provider frustration with the consent process. Over 6 months, we
      determined the average number of hospitalisations requiring transfusions in a
      random sampling of haematology/oncology/BMT inpatients. We surveyed nurses and
      providers regarding frustration levels and contact required regarding consents.
      Four and 12 months after implementation of the annual consent, providers and
      nurses were resurveyed, and new inpatient cohorts were assessed. Comparison of
      preintervention and postintervention time data allowed calculation of provider
      time reduction, a surrogate measure of improved work efficiency. Prior to the
      annual consent, >33 hours were spent over 6 months obtaining consent on 40
      patients, with >19 hours spent obtaining consent when no transfusions were
      administered during admission. Twelve months after annual consent implementation,
      97.5% (39/40) of analysed patients had a completed annual blood products
      transfusion consent and provider work efficiency had improved by 94.6% (>30
      hours). Although several surveyed variables improved following annual consent
      implementation, provider frustration with consent process remained 6 out of a max
      score of 10, the same level as prior to the intervention. Development of an
      annual inpatient blood products consent form decreased provider time from 15 to
      <1 min per admission, decreased consenting numbers and increased work efficiency
      by >90%.

PMID- 29333498
TI  - Impact of pharmacist-led antibiotic stewardship program in a PICU of low/middle
      income country.

PMID- 29333499
TI  - Sick Note to Fit Note: one trust's project to improve usage by hospital
      clinicians.
AB  - Introduction: In April 2010, the government introduced a new Statement of Fitness
      to Work or 'Fit Note' for patients requiring time off of work or adaptations to
      their work due to illness. Responsibility to issue these documents has shifted
      from primary to secondary care. Hospital clinicians are required to issue for
      inpatients and for outpatients where clinical responsibility has not been taken
      over by the general practitioner (GP). However, awareness of this change is
      lacking. Misdirecting patients to their GP for the sole purpose of receiving a
      'Fit Note' is an unnecessary use of appointment time and negatively impacts on
      patients. King's College Hospital NHS Trust receives a number of quality alerts
      from primary care regarding this issue. Methods: A trust-wide educational
      initiative was designed and implemented to increase staff awareness of Fit Notes
      and their correct usage in order to reduce the number of patients being
      misdirected to their GP to obtain one. Interventions included direct staff
      engagement, a trust-wide promotional campaign and creation of an electronic
      version of the document. Results: Uptake of the electronic version of the Fit
      Note has steadily increased and there has been a fall in the number of quality
      alerts received by the trust. However, staff awareness on the whole remains low.
      Conclusions: Patients being misdirected to their general practice for Fit Notes
      is an important issue and one on which the baseline level of awareness among
      hospital clinicians is low. Challenges during this intervention have been in
      penetrating a trust of this size and getting the message across to staff.
      However, digitising the Fit Note can help to increase its use.

PMID- 29333500
TI  - Improving the Written Medical Handover.
AB  - The handover of large numbers of medical patients, during on call periods when
      staffing levels are reduced, is a challenge for all acute medical services. At
      the Royal Cornwall Hospital, a large district general hospital, we identified
      that foundation doctors were reviewing medical inpatients during weekend on call
      periods with limited written handover information. We chose to address this
      problem by developing an intervention, a weekend handover sticker, and piloting
      it. We used the review of documentation to measure improvement and feedback from
      users to assess the processes involved. Use of the weekend handover form improved
      the written communication between weekday and weekend teams. The number of
      weekend plans documented in the notes increased from 15% to 84% and the provision
      of a patient summary within the last 7 days increased from 26% to 94%. The
      feedback from users confirmed it was a useful intervention and 100% (15/15) of
      doctors and nurses responded positively to the question "Do you think the weekend
      sticker should be introduced and used at the weekend for all medical patients?"
      The feedback also identified concerns regarding additional workload for weekday
      ward staff and this has led to ongoing work to try and ensure that the weekend
      handover form continues to be used effectively to maintain an improved level of
      written handover information for on call staff. While we have not included a
      direct measure of patient care, we hope that by improving the quality of written
      handover information we are acting to ensure patient information is shared
      effectively, with likely positive impact on patient care.

PMID- 29333501
TI  - Feasibility of conducting intradermal vaccination campaign with inactivated
      poliovirus vaccine using Tropis intradermal needle free injection system,
      Karachi, Pakistan.
AB  - Background: Administration of intradermal fractional dose of inactivated
      poliovirus vaccine (fIPV) has proven to be safe and immunogenic; however, its
      intradermal application using needle and syringe is technically difficult and
      requires trained personnel. Methods: We assessed feasibility of conducting an
      intradermal fIPV campaign in polio high risk neighborhood of Karachi using Tropis
      needle-free injector. During the one-day fIPV campaign, we measured average
      "application time" to administer fIPV with Tropis, collected ergonomic
      information and measured vaccine wastage. Results: Eleven vaccinator teams, after
      two-day training, immunized 582 children between 4 months and 5 years of age.
      Average "application time" ranged from 35-75 seconds; the "application time"
      decreased with the number of children vaccinated from 68 to 38 seconds between
      1st and 30th child. 10/11 (91%) vaccinator teams found no ergonomic issues; 1/11
      (9%) assessed that it was not easy to remove air bubbles when filling the device.
      There was 0% vaccine loss reported. No adverse events following immunizations
      were reported. Interpretation: We demonstrated that it is feasible, safe and
      efficient to use Tropis for the administration of fIPV in a campaign setting.

PMID- 29333502
TI  - Unresectable cutaneous squamous cell carcinoma of the forehead with MLH1 mutation
      showing dramatic response to Programmed Cell Death Protein 1 Inhibitor Therapy.
AB  - Treatment of refractory, unresectable cutaneous squamous cell carcinoma presents
      a great challenge in head and neck oncology with poor prognosis. Prior case
      reports have shown off-label pembrolizumab, a programed cell death receptor
      antagonist, can be effective in unresectable cutaneous squamous cell carcinoma.
      Furthermore, prior reports have suggested enhanced efficacy when high mutational
      burden is present. In this study we present a severe case of unresectable
      cutaneous squamous cell carcinoma invading the orbit and cavernous sinus with
      documented tumor MLH1 mutation. The patient had a complete response to
      palliative, off-label pembrolizumab therapy.

PMID- 29333503
TI  - The Effect of a Vegan versus AHA DiEt in Coronary Artery Disease (EVADE CAD)
      trial: study design and rationale.
AB  - Background: Multiple studies demonstrate the benefit of a vegan diet on
      cardiovascular risk factors when compared to no intervention or usual dietary
      patterns. The aim of this study is to evaluate the effect of a vegan diet versus
      the American Heart Association (AHA)-recommended diet on inflammatory and
      glucometabolic profiles in patients with angiographically defined coronary artery
      disease (CAD). Study Design: This study is a randomized, open label, blinded end
      point trial of 100 patients with CAD as defined by >=50% diameter stenosis in a
      coronary artery >=2 mm in diameter on invasive angiography. Participants are
      randomized to 8 weeks of either a vegan or AHA-recommended diet (March 2014 and
      February 2017). Participants are provided weekly groceries that adhere to the
      guidelines of their diet. The primary endpoint is high sensitivity C-reactive
      concentrations. Secondary endpoints include anthropometric data, other markers of
      inflammation, lipid parameters, glycemic markers, endothelial function, quality
      of life data, and assessment of physical activity. Endpoints are measured at each
      visit (baseline, 4 weeks, and 8 weeks). Dietary adherence is measured by two
      weekly 24-hour dietary recalls, a 4-day food record during the week prior to each
      visit, and both plasma and urine levels of trimethylamine-N-oxide at each visit.
      Conclusion: This study is the first to comprehensively assess multiple indices of
      inflammation and glucometabolic profile in a rigorously conducted randomized
      trial of patients with CAD on a vegan versus AHA-recommended diet.

PMID- 29333504
TI  - Community-based physical activity as adjunctive smoking cessation treatment:
      Rationale, design, and baseline data for the Lifestyle Enhancement Program (LEAP)
      randomized controlled trial.
AB  - Despite advances in behavioral and pharmacological treatment for tobacco use and
      dependence, quit rates remain suboptimal. Increasing physical activity has shown
      some promise as a strategy for improving cessation outcomes. However, initial
      efficacy studies focused on intensive, highly structured exercise programs that
      may not be applicable to the general population of smokers. We describe the
      rationale and study design and report baseline participant characteristics from
      the Lifestyle Enhancement Program (LEAP), a two-group, randomized controlled
      trial. Adult smokers who engaged in low levels of leisure time physical activity
      were randomly assigned to treatment conditions consisting of an individualized
      physical activity intervention delivered by health fitness instructors in
      community-based exercise facilities or an equal contact wellness control. All
      participants received standard cognitive behavioral smoking cessation counseling
      combined with nicotine replacement therapy. The primary outcomes are seven-day
      point prevalence abstinence at seven weeks, six- and 12 months. Secondary
      outcomes include self-reported physical activity, dietary intake, body mass
      index, waist circumference, percent body fat, and nicotine withdrawal symptoms.
      Participants consist of 392 sedentary smokers (mean [standard deviation] age =
      44.6 [10.2] = years; 62% female; 31% African American). Results reported here
      provide information regarding experiences recruiting smokers willing to change
      multiple health behaviors including smoking and physical activity.

PMID- 29333505
TI  - Toxicological Implications of Released Particulate Matter during Thermal
      Decomposition of Nano-Enabled Thermoplastics.
AB  - Nano-enabled thermoplastics are part of the growing market of nano-enabled
      products (NEPs) that have vast utility in several industries and consumer goods.
      The use and disposal of NEPs at their end of life has raised concerns about the
      potential release of constituent engineered nanomaterials (ENMs) during thermal
      decomposition and their impact on environmental health and safety. To investigate
      this issue, industrially relevant nano-enabled thermoplastics including
      polyurethane, polycarbonate, and polypropylene containing carbon nanotubes (0.1
      and 3% w/v, respectively), polyethylene containing nanoscale iron oxide (5% w/v),
      and ethylene vinyl acetate containing nanoscale titania (2 and 5% w/v) along with
      their pure thermoplastic matrices were thermally decomposed using the recently
      developed lab based Integrated Exposure Generation System (INEXS). The life cycle
      released particulate matter (called LCPM) was monitored using real time
      instrumentation, size fractionated, sampled, extracted and prepared for
      toxicological analysis using primary small airway epithelial cells to assess
      potential toxicological effects. Various cellular assays were used to assess
      reactive oxygen species and total glutathione as measurements of oxidative stress
      along with mitochondrial function, cellular viability, and DNA damage. By
      comparing toxicological profiles of LCPM released from polymer only (control)
      with nano-enabled LCPM, potential nanofiller effects due to the use of ENMs were
      determined. We observed associations between NEP properties such as the percent
      nanofiller loading, host matrix, and nanofiller chemical composition and the
      physico-chemical properties of released LCPM, which were linked to biological
      outcomes. More specifically, an increase in percent nanofiller loading promoted a
      toxicological response independent of increasing LCPM dose. Importantly,
      differences in host matrix and nanofiller composition were shown to enhance
      biological activity and toxicity of LCPM. This work highlights the importance of
      assessing the toxicological properties of LCPM and raises environmental health
      and safety concerns of nano-enabled products at their end of life during thermal
      decomposition/incineration.

PMID- 29333507
TI  - Platinum open access journal in urology.

PMID- 29333508
TI  - Role of cytoreductive nephrectomy in the targeted therapy era: A systematic
      review and meta-analysis.
AB  - Purpose: To determine the effectiveness and harm of cytoreductive nephrectomy
      versus no intervention in patients with metastatic renal carcinoma who undergo
      targeted therapy to improve overall survival. Materials and Methods: A search
      strategy was conducted in the MEDLINE, CENTRAL, Embase, HTA, DARE, NHS, and
      LILACS databases. Searches were also conducted for unpublished literature through
      references from relevant articles identified through the search, conferences,
      thesis databases, OpenGrey, Google Scholar, and clinicaltrials.gov, among others.
      Studies were included without language restrictions. The risk of bias assessment
      was made by using a modified Cochrane Collaboration tool. A meta-analysis of
      fixed effects was conducted. The expected outcomes were overall survival, quality
      of life, adverse effects, mortality, and progression- free survival. The measure
      of the effect was the hazard ratio (HR) with a 95% confidence interval (CI). The
      planned comparison was cytoreductive nephrectomy versus no intervention. Results:
      A total of 22,507 patients were found among seven studies. Seven studies were
      included in the qualitative analysis (eight publications) and five in the
      quantitative analysis for overall survival. One study reported progression-free
      survival and one reported targeted therapy toxicities. A low risk of bias was
      shown for most of the study items. The HR for overall survival was 0.58 (95% CI,
      0.50 to 0.65) favoring cytoreductive nephrectomy compared with no intervention.
      Conclusions: Cytoreductive nephrectomy is effective for improving overall
      survival in patients with metastatic renal carcinoma who undergo targeted therapy
      compared with no intervention.

PMID- 29333509
TI  - Rate and association of lower urinary tract infection with recurrence after
      transurethral resection of bladder tumor.
AB  - Purpose: To evaluate the rate of pyuria and bacteriuria after transurethral
      resection of bladder tumor (TURBT). Materials and Methods: We retrospectively
      evaluated data obtained from 363 patients who underwent TURBT between October
      2012 and December 2013 at Seoul National University Hospital. Urinalysis and
      urine culture were assessed at 3, 6, 12, and 24 months postoperatively. Primary
      endpoint was the rate of bacteriuria (>=105/mL in a midstream) and pyuria (white
      blood cells >=5/high-power field). Results: We analyzed 306 patients who were
      eligible for the study. Pyuria was present in 23.5% of patients in the 3rd
      postoperative month and in 31.7% of patients in the 24th postoperative month.
      Bacteriuria was present in 1.3% of patients in the 3rd postoperative month and in
      2.6% of patients in the 24th postoperative month. Among urothelial carcinoma
      patients (n=220), 24.1% showed pyuria and 1.8% showed bacteriuria at the 3rd
      postoperative month. We found that 31.8% showed pyuria and 3.2% showed
      bacteriuria at the 24th postoperative month. There was no significant difference
      in the rate of pyuria and bacteriuria between the intravesical treatment group
      and the no-treatment group. Multivariate analysis demonstrated that pyuria in the
      3rd postoperative month (odd ratio [OR], 2.254; p=0.039), tumor multiplicity (OR,
      3.331; p=0.001), and the absence of intravesical treatment (OR, 4.927; p=0.001)
      increases the risk of tumor recurrence. Conclusions: A significant proportion of
      patients showed pyuria after TURBT during the follow-up period. Additionally,
      presence of pyuria in the short-term follow-up period after TURBT constitutes a
      risk factor for recurrence of bladder cancer.

PMID- 29333510
TI  - Factors associated with testosterone recovery after androgen deprivation therapy
      in patients with prostate cancer.
AB  - Purpose: We investigated factors affecting testosterone recovery after androgen
      deprivation therapy (ADT) withdrawal in patients with prostate cancer. Materials
      and Methods: The medical records of patients who underwent radical prostatectomy
      with ADT were retrospectively reviewed. In all, 221 patients were included in the
      analysis. Testosterone recovery was defined as supra-castration (SC)
      (testosterone levels in serum >50 ng/dL) or out of hypogonadism (OH) (>300 ng/dL)
      after ADT withdrawal. Kaplan-Meier analyses were used to estimate testosterone
      recovery after ADT cessation. Cox regression analyses were used to determine the
      factors affecting the recovery of testosterone. Results: After ADT, 206 patients
      (93.2%) recovered to the SC level and 122 patients (55.2%) recovered to the OH
      level. Patients treated with ADT for <=18 months recovered to OH in a mean of 6.8
      months (74.6%), but patients treated with ADT for >18 months recovered in a mean
      of 9.7 months (27.5%). In multivariate analyses, age (hazard ratio [HR], 0.915;
      p<0.001), serum level of sex hormone-binding globulin (SHBG) (HR, 1.015;
      p=0.002), initial testosterone level (HR, 1.002; p=0.002), and ADT duration (HR,
      0.915; p<0.001) were associated with recovery to the OH level after ADT
      withdrawal, and hypertension (HR, 0.697; p=0.029) and duration of ADT (HR, 0.979;
      p=0.012) were significantly associated with recovery to SC. Conclusions: In
      patients treated with ADT for <=18 months, testosterone recovers to the OH level
      more often and faster after ADT cessation. Age, SHBG level, initial testosterone
      level, and ADT duration are associated with testosterone recovery.

PMID- 29333511
TI  - Evaluating the importance of different computed tomography scan-based factors in
      predicting the outcome of extracorporeal shock wave lithotripsy for renal stones.
AB  - Purpose: To evaluate the impact of various computed tomography scan-based
      parameters of renal stones on the outcome of extracorporeal shock wave
      lithotripsy (ESWL). Materials and Methods: We conducted a retrospective study of
      patients who underwent ESWL for renal stones (sized 5-20 mm) from January 2013 to
      December 2016. We evaluated body mass index, location of the stone, skin-to-stone
      distance (SSD), stone attenuation value (SAV), stone diameter, Hounsfield
      density, stone area, and stone volume. Statistical analysis was done and
      significance was confirmed by multivariate logistic regression analysis. Results:
      Of the 203 patients 122 (60.1%) had successful clearance of the stone. The
      presence of a double J stenting, a lower pole location, a higher SAV, higher
      Hounsfield density, larger stone area, larger stone diameter, and higher stone
      volume were negative predictors of ESWL outcome. When these parameters were
      analyzed with multivariate logistic regression analysis, stone location, SSD, and
      SAV were the only significant independent predictors of the outcome of ESWL.
      Conclusions: Stone location, SSD, and SAV are reliable and strong predictors of
      ESWL outcome for the treatment of renal stones.

PMID- 29333512
TI  - Fourier transform infrared spectroscopy for analysis of kidney stones.
AB  - Purpose: To compare the results of a chemical method of kidney stone analysis
      with the results of Fourier transform infrared (FT-IR) spectroscopy. Materials
      and Methods: Kidney stones collected between June and October 2015 were
      simultaneously analyzed by chemical and FT-IR methods. Results: Kidney stones
      (n=449) were collected from patients from 1 to 81 years old. Most stones were
      from adults, with only 11.5% from children (aged 3-16 years) and 1.5% from
      children aged <2 years. The male to female ratio was 4.6. In adults, the calcium
      oxalate stone type, calcium oxalate monohydrate (COM, n=224), was the most common
      crystal, followed by uric acid and calcium oxalate dihydrate (COD, n=83). In
      children, the most frequently occurring type was predominantly COD (n=21),
      followed by COM (n=11), ammonium urate (n=10), carbonate apatite (n=6), uric acid
      (n=4), and cystine (n=1). Core composition in 22 stones showed ammonium urate
      (n=2), COM (n=2), and carbonate apatite (n=1) in five stones, while uric acid
      crystals were detected (n=13) by FT-IR. While chemical analysis identified 3
      stones as uric acid and the rest as calcium oxalate only. Agreement between the
      two methods was moderate, with a kappa statistic of 0.57 (95% confidence
      interval, 0.5-0.64). Disagreement was noted in the analysis of 77 stones.
      Conclusions: FT-IR analysis of kidney stones can overcome many limitations
      associated with chemical analysis.

PMID- 29333513
TI  - Can feeling of incomplete bladder emptying reflect significant postvoid residual
      urine? Is it reliable as a symptom solely?
AB  - Purpose: The main objective of this study was to reveal the relationship between
      lower urinary tract symptoms (LUTS) and post-void residual (PVR) urine volume.
      Materials and Methods: Between October 2014 and February 2015, older than 40
      years patients were included in this study. Volunteers filled out a questionnaire
      consisted of demographic characteristics, comorbidities, medications, history of
      surgery and LUTS. Volunteers were undergone PVR measurement with transabdominal
      ultrasonography. The relationship between symptoms, demographic characteristics
      and PVR were analyzed. Results: A total of 939 patients (756 men and 183 women)
      were enrolled in this study. There was a positive correlation between the
      sensation of incomplete bladder emptying and PVR volume in all age groups of
      women (p=0.0001). However such a relationship was found only over the age of 60
      in the subgroup analysis of men (p=0.001). PVR volume increased in men by age
      (0.65 mL per year of age, p=0.011). In men, voiding symptoms and urgency were
      associated with a high PVR volume. In women, storage and voiding symptoms (except
      slow stream and terminal dribble) did not correlate with PVR volume. Conclusions:
      Our study showed that all men over the age of 60 years and all women with the
      complaint of feeling of incomplete emptying should undergone PVR measurement.
      Women with the complaint of poor stream and men mainly with voiding symptoms are
      other candidates in whom PVR measurement would be considered as an important tool
      in the clinical management and follow-up.

PMID- 29333514
TI  - What is the fate of artificial urinary sphincters among men undergoing repetitive
      bladder cancer treatment?
AB  - Purpose: Functional characteristics and durability of the artificial urinary
      sphincter (AUS) among patients who develop bladder cancer has been poorly
      characterized. We sought to evaluate AUS outcomes among patients subsequently
      diagnosed with bladder cancer, in order to describe device survivability when
      subject to diagnostic and therapeutic procedures such as cystoscopy,
      transurethral resection, and cystectomy. Materials and Methods: We
      retrospectively reviewed 1,803 male patients treated with AUS surgery at a single
      institution between 1983-2014. We describe AUS device outcomes among patients
      undergoing surveillance and treatment for bladder cancer. Results: Following AUS
      placement, 14 (0.8%) patients were subsequently diagnosed with and treated for
      bladder cancer and 4 patients with bladder cancer undergoing treatment and
      screening, subsequently received AUS placement. The median follow-up from device
      placement was 7.2 years (interquartile range [IQR], 2.8-11.5), and the median
      time from AUS placement to bladder cancer diagnosis was 6 (IQR, 0-9). There were
      a total of 8 primary and 1 secondary devices failures. Despite a median of 2
      diagnostic cystoscopies (IQR, 1-6) and 0 bladder tumor resections (IQR, 0-0) per
      patient following device implantation, only 1 (5.6%) patient experienced an
      iatrogenic erosion related to urethral manipulation. Among those undergoing
      cystectomy (n=4), 1 device was left in situ without complication. Conclusions:
      Bladder cancer surveillance and treatment with an AUS device in place appears to
      confer minimal additional risk to AUS survival. Careful attention should be given
      to device deactivation and use of the smallest caliber instruments available to
      minimize the risk of iatrogenic urethral erosion.

PMID- 29333506
TI  - Murine Models of Heart Failure with Preserved Ejection Fraction: a "Fishing
      Expedition".
AB  - Heart failure with preserved ejection fraction (HFpEF) is characterized by signs
      and symptoms of HF in the presence of a normal left ventricular (LV) ejection
      fraction (EF). Despite accounting for up to 50% of all clinical presentations of
      HF, the mechanisms implicated in HFpEF are poorly understood, thus precluding
      effective therapy. The pathophysiological heterogeneity in the HFpEF phenotype
      also contributes to this disease and likely to the absence of evidence-based
      therapies. Limited access to human samples and imperfect animal models that
      completely recapitulate the human HFpEF phenotype have impeded our understanding
      of the mechanistic underpinnings that exist in this disease. Aging and
      comorbidities such as atrial fibrillation, hypertension, diabetes and obesity,
      pulmonary hypertension and renal dysfunction are highly associated with HFpEF.
      Yet, the relationship and contribution between them remains ill-defined. This
      review discusses some of the distinctive clinical features of HFpEF in
      association with these comorbidities and highlights the advantages and
      disadvantage of commonly used murine models, used to study the HFpEF phenotype.

PMID- 29333515
TI  - Changes in autonomic nervous system activity after treatment with alpha-blocker
      in men with lower urinary tract symptoms.
AB  - Purpose: To determine changes in autonomic nervous system activity after
      treatment in men with lower urinary tract symptoms (LUTS), we evaluated changes
      in patients' symptoms, uroflowmetry, and heart rate variability (HRV) after
      treatment with alpha-blockers for 12 weeks. Materials and Methods: Ninety-five
      men who had LUTS (International Prostate Symptom Score [IPSS] >=8) were included
      in this study. We divided them into two groups on the basis of a low
      frequency/high frequency (LF/HF) ratio of 1.6. After treatment with Xatral XL
      (Handok Inc., Korea) 10 mg for 3 months, we rechecked their IPSS, uroflowmetry,
      HRV and compared these with the baseline measurements. Results: Fifty-four men
      were assigned to the low LF/HF group (group A: LF/HF <=1.6) and 41 men to the
      high LF/HF group (group B: LF/HF >1.6). At baseline and 12 weeks, none of the
      parameters differed significantly between the groups except for HF, which is one
      of the parameters of HRV. IPSS, the IPSS-voiding subscore, and the IPSS-storage
      subscore decreased and maximal uroflow increased significantly after 12 weeks of
      treatment. Whereas the baseline LF/HF ratio increased from 0.89+/-0.407 to 1.80+/
      1.804 after treatment in group A, it decreased from 3.93+/-5.471 to 1.79+/-1.153
      in group B. Conclusions: The efficacies of Xatral XL were clear in both groups.
      We found that the LF/HF ratio in the two groups merged to a value of
      approximately 1.79 after treatment. We suggest that this could be a clue to the
      importance of balance in autonomic nervous system activity in men with LUTS.

PMID- 29333516
TI  - Comparison of penile length at 6-24 months between children with unilateral
      cryptorchidism and a healthy normal cohort.
AB  - Purpose: Urologic diseases affected by testosterone can be associated with
      smaller penis size compared to the normal population. We sought to compare penile
      length in children with unilateral cryptorchidism and normative data from a
      cohort of healthy Korean boys. Materials and Methods: This study was performed in
      259 Korean boys (212, normal cohort; 47, cryptorchidism) aged 6-24 months, each
      of whom had been brought to an outpatient clinic at one of five tertiary
      hospitals (Gyeongsangnam-do Province) between April 2014 and June 2015. Penile
      length was measured via stretched penile length (SPL) and testicular size was
      measured using orchidometry (mL). Results: SPL in children with cryptorchidism
      was significantly shorter compared to a cohort of healthy Korean boys aged 6-24
      months (3.7+/-0.5 cm and 4.3+/-0.8 cm, p<0.001), although there were no
      differences with regard to height, body weight and contralateral testicular size
      between the two groups. According to the stratified ages (6-12, 12-18, and 18-24
      months), SPL in children with cryptorchidism was persistently shorter at their
      ages than those without. Conclusions: It might be that the penile length aged 6
      24 months of children with unilateral cryptorchidism is shorter than that of a
      cohort of healthy Korean boys.

PMID- 29333517
TI  - Safety and feasibility of platelet rich fibrin matrix injections for treatment of
      common urologic conditions.
AB  - Purpose: Autologous platelet rich plasma (PRP) is used increasingly in a variety
      of settings. PRP injections have been used for decades to improve angiogenesis
      and wound healing. They have also been offered commercially in urology with
      little to no data on safety or efficacy. PRP could theoretically improve multiple
      urologic conditions, such as erectile dysfunction (ED), Peyronie's disease (PD),
      and stress urinary incontinence (SUI). A concern with PRP, however, is early
      washout, a situation potentially avoided by conversion to platelet rich fibrin
      matrix (PRFM). Before clinical trials can be performed, safety analysis is
      desirable. We reviewed an initial series of patients receiving PRFM for urologic
      pathology to assess safety and feasibility. Materials and Methods: Data were
      reviewed for patients treated with PRFM at our center from November 2012 to July
      2017. Patients were observed immediately post-injection and at follow-up for
      complications and tolerability. Where applicable, International Index of Erectile
      Function (IIEF-5) scores were reviewed before and after injections for ED and/or
      PD. Pad use data was collected pre/post injection for SUI. Results: Seventeen
      patients were identified, with a mean receipt of 2.1 injections per patient. Post
      procedural minor adverse events were seen in 3 men, consisting of mild pain at
      injection site and mild penile bruising. No patients experienced complications at
      follow-up. No decline was observed in men completing pre/post IIEF-5 evaluations.
      Conclusions: PRFM appears to be a safe and feasible treatment modality in
      patients with urologic disease. Further placebo-controlled trials are warranted.

PMID- 29333518
TI  - Letter to the editor: Urethral strictures after bipolar transurethral resection
      of prostate may be linked to slow resection rate.

PMID- 29333519
TI  - The authors reply: Urethral strictures after bipolar transurethral resection of
      prostate may be linked to slow resection rate.

PMID- 29333520
TI  - Application of epigenetic data in human health risk assessment.
AB  - Despite the many recent advances in the field of epigenetics, application of this
      knowledge in environmental health risk assessment has been limited. In this
      paper, we identify opportunities for application of epigenetic data to support
      health risk assessment. We consider current applications and present a vision for
      the future.

PMID- 29333521
TI  - Nanomaterials for convection-enhanced delivery of agents to treat brain tumors.
AB  - Nanomaterials represent a promising and versatile platform for the delivery of
      therapeutics to the brain. Treatment of brain tumors has been a long-standing
      challenge in the field of neuro-oncology. The current standard of care - a
      multimodal approach of surgery, radiation and chemotherapy - yields only a modest
      therapeutic benefit for patients with malignant gliomas. A major obstacle for
      treatment is the failure to achieve sufficient delivery of therapeutics at the
      tumor site. Recent advances in local drug delivery techniques, along with the
      development of highly effective brain-penetrating nanocarriers, have
      significantly improved treatment and imaging of brain tumors in preclinical
      studies. The major advantage of this combined strategy is the ability to optimize
      local therapy, by maintaining an effective and sustained concentration of
      therapeutics in the brain with minimal systemic toxicity. This review highlights
      some of the latest developments, significant advancements and current challenges
      in local delivery of nanomaterials for the treatment of brain tumors.

PMID- 29333522
TI  - Impact of HLA Class I Alleles on Timing of HIV Rebound After Antiretroviral
      Treatment Interruption.
AB  - Background: Identifying host determinants associated with HIV reservoir size and
      timing of viral rebound after an analytic treatment interruption (ATI) is an
      important step in the search for an HIV functional cure. We performed a pooled
      analysis of 103 participants from 4 AIDS Clinical Trials Group ATI studies to
      identify the association between HLA class I alleles with HIV reservoir size and
      viral rebound timing. Methods: Total HIV DNA and cell-associated HIV RNA (CA-RNA)
      were quantified in pre-ATI peripheral blood mononuclear cell samples, and
      residual plasma viremia was measured using the single-copy assay. HLA class I
      typing was performed, and we generated an odds ratio (OR) of predicted HLA effect
      on HIV viremia control for each individual and compared this with time to viral
      rebound, and levels of HIV DNA and CA-RNA. Results: There was no significant
      association between the HLA ORs and levels of HIV DNA or CA-RNA, but carriage of
      protective HLA-B alleles (lower OR scores) was associated with delayed viral
      rebound (P = 0.02). Higher OR scores at the HLA-C locus were associated with
      longer duration of ART treatment (P = 0.02) and this trend was also seen with the
      combined OR score (P < 0.01). Individuals with protective HLA-B alleles had
      delayed viral rebound after treatment interruption that was not explained by
      differences in baseline reservoir size. Conclusions: The results indicate the
      vital role of cellular host immunity in preventing HIV rebound and the importance
      of taking into account the HLA status of study participants being evaluated in
      trials for an HIV cure.

PMID- 29333523
TI  - Spin-orbit torques from interfacial spin-orbit coupling for various interfaces.
AB  - We use a perturbative approach to study the effects of interfacial spin-orbit
      coupling in magnetic multilayers by treating the two-dimensional Rashba model in
      a fully three-dimensional description of electron transport near an interface.
      This formalism provides a compact analytic expression for current-induced spin
      orbit torques in terms of unperturbed scattering coefficients, allowing
      computation of spin-orbit torques for various contexts, by simply substituting
      scattering coefficients into the formulas. It applies to calculations of spin
      orbit torques for magnetic bilayers with bulk magnetism, those with interface
      magnetism, a normal metal/ferromagnetic insulator junction, and a topological
      insulator/ferromagnet junction. It predicts a dampinglike component of spin-orbit
      torque that is distinct from any intrinsic contribution or those that arise from
      particular spin relaxation mechanisms. We discuss the effects of proximity
      induced magnetism and insertion of an additional layer and provide formulas for
      in-plane current, which is induced by a perpendicular bias, anisotropic
      magnetoresistance, and spin memory loss in the same formalism.

PMID- 29333524
TI  - Resonant X-ray Emission of Hexagonal Boron Nitride.
AB  - The electronic structure of hexagonal boron nitride (h-BN) is explored using
      measurements of x-ray absorption and resonant inelastic x-ray scattering (RIXS)
      at the nitrogen K edge (1s) in tandem with calculations using many-body
      perturbation theory within the GW and Bethe-Salpeter equation (BSE)
      approximations. Our calculations include the effects of lattice disorder from
      phonons activated thermally and from zero point energy. They highlight the
      influence of disorder on near-edge x-ray spectra.

PMID- 29333525
TI  - Dyslipidemia and its Correlates among HIV Infected Children on HAART Attending
      Mbarara Regional Referral Hospital.
AB  - Background: HAART and chronic HIV associated inflammation has been attributed to
      abnormal lipids in HIV infected people. Little is known about dyslipidemia among
      children in Uganda in the era of increasing Highly Active Anti Retroviral Therapy
      (HAART) use. We determined the prevalence of lipid abnormalities, the correlation
      of the lipid abnormalities to CD4 count, HIV clinical stage and duration on HAART
      among HIV infected children. Methods: This was a cross-sectional, descriptive and
      analytical study of HIV infected children age 1-17 years receiving HAART for more
      than 6 months in Mbarara Regional Referral Hospital. Consent and assent were
      obtained as appropriate. Sociodemographic, clinical and immunological data were
      collected and recorded in a questionnaire. A blood sample was taken for lipid
      profiling. Dyslipidemia was defined as any low HDL (<=40mg/dl), high LDL
      (>130mg/dl), high TG (>130mg/dl) and a high total cholesterol (>200mg/dl) or a
      combination of these in the study population. The proportion of children with
      dyslipidemia was calculated and logistic regression analysis for associated
      factors. Results: The mean age was 118 months (SD 49 months) with 49.5% of the
      children male and 62.1% had severe HIV disease at initiation of HAART. Mean
      duration of HAART was 55.6 months (SD 31.2 months). The prevalence of
      dyslipidemia was 74%. Among the children with dyslipidemia, 56.6% exhibited low
      HDL, 22% had hypertriglyceridemia, 15.6% had high LDL and 11% had
      hypercholesterolemia. We found significant association between dyslipidemia and
      WHO clinical stage at initiation of HAART (AOR 2.9 1.05 - 8.45 p=0.040).
      Conclusion: There was a high prevalence of dyslipidemia associated with severe
      HIV disease at initiation of HAART among HIV-infected children on HAART.

PMID- 29333526
TI  - Next-Generation Rapid Autopsies Enable Tumor Evolution Tracking and Generation of
      Preclinical Models.
AB  - Purpose: Patients with cancer who graciously consent for autopsy represent an
      invaluable resource for the study of cancer biology. To advance the study of
      tumor evolution, metastases, and resistance to treatment, we developed a next
      generation rapid autopsy program integrated within a broader precision medicine
      clinical trial that interrogates pre- and postmortem tissue samples for patients
      of all ages and cancer types. Materials and Methods: One hundred twenty-three
      (22%) of 554 patients who consented to the clinical trial also consented for
      rapid autopsy. This report comprises the first 15 autopsies, including patients
      with metastatic carcinoma (n = 10), melanoma (n = 1), and glioma (n = 4). Whole
      exome sequencing (WES) was performed on frozen autopsy tumor samples from
      multiple anatomic sites and on non-neoplastic tissue. RNA sequencing (RNA-Seq)
      was performed on a subset of frozen samples. Tissue was also used for the
      development of preclinical models, including tumor organoids and patient-derived
      xenografts. Results: Three hundred forty-six frozen samples were procured in
      total. WES was performed on 113 samples and RNA-Seq on 72 samples. Successful
      cell strain, tumor organoid, and/or patient-derived xenograft development was
      achieved in four samples, including an inoperable pediatric glioma. WES data were
      used to assess clonal evolution and molecular heterogeneity of tumors in
      individual patients. Mutational profiles of primary tumors and metastases yielded
      candidate mediators of metastatic spread and organotropism including CUL9 and
      PIGM in metastatic ependymoma and ANKRD52 in metastatic melanoma to the lung. RNA
      Seq data identified novel gene fusion candidates. Conclusion: A next-generation
      sequencing-based autopsy program in conjunction with a pre-mortem precision
      medicine pipeline for diverse tumors affords a valuable window into clonal
      evolution, metastasis, and alterations underlying treatment. Moreover, such an
      autopsy program yields robust preclinical models of disease.

PMID- 29333527
TI  - Impact of Genetic Ancestry on Outcomes in ECOG-ACRIN-E5103.
AB  - Purpose: Racial disparity in breast cancer outcomes exists between African
      American and Caucasian women in the United States. We have evaluated the impact
      of genetically determined ancestry on disparity in efficacy and therapy-induced
      toxicity for breast cancer patients in the context of a randomized, phase III
      adjuvant trial. Patients and Methods: This study compared outcomes between 386
      patients of African ancestry (AA) and 2473 patients of European ancestry (EA) in
      a randomized, phase III breast cancer trial; ECOG-ACRIN-E5103. The primary
      efficacy endpoint, invasive disease free survival (DFS) and clinically
      significant toxicities were compared including: anthracycline-induced congestive
      heart failure (CHF), taxane-induced peripheral neuropathy (TIPN), and bevacizumab
      induced hypertension. Results: Overall, AAs had significantly inferior DFS
      (p=0.002; HR=1.5) compared with EAs. This was significant in the estrogen
      receptor-positive subgroup (p=0.03); with a similar, non-significant trend for
      those who had triple negative breast cancer (TNBC; p=0.12). AAs also had
      significantly more grade 3-4 TIPN (OR=2.9; p=2.4 *10-11) and grade 3-4
      bevacizumab-induced hypertension (OR=1.6; p=0.02), with a trend for more CHF
      (OR=1.8; p=0.08). AAs had significantly more dose reductions for paclitaxel
      (p=6.6 *10-6). In AAs, dose reductions in paclitaxel had a significant negative
      impact on DFS (p=0.03); whereas in EAs, dose reductions did not impact outcome
      (p=0.35). Conclusion: AAs had inferior DFS with more clinically important
      toxicities in ECOG-ACRIN-E5103. The altered risk to benefit ratio for adjuvant
      breast cancer chemotherapy should lead to additional research with the focus
      centered on the impact of genetic ancestry on both efficacy and toxicity.
      Strategies to minimize dose reductions for paclitaxel, especially due to TIPN,
      are warranted for this population.

PMID- 29333529
TI  - Promoting resilience in diverse classrooms: The answers are not in the back of
      the book.

PMID- 29333528
TI  - Patterns of Metastatic Spread and Mechanisms of Resistance to Crizotinib in ROS1
      Positive Non-Small-Cell Lung Cancer.
AB  - PURPOSE: The ROS1 tyrosine kinase is activated through ROS1 gene rearrangements
      in 1-2% of non-small cell lung cancer (NSCLC), conferring sensitivity to
      treatment with the ALK/ROS1/MET inhibitor crizotinib. Currently, insights into
      patterns of metastatic spread and mechanisms of crizotinib resistance among ROS1
      positive patients are limited. PATIENTS AND METHODS: We reviewed clinical and
      radiographic imaging data of patients with ROS1- and ALK-positive NSCLC in order
      to compare patterns of metastatic spread at initial metastatic diagnosis. To
      determine molecular mechanisms of crizotinib resistance, we also analyzed repeat
      biopsies from a cohort of ROS1-positive patients progressing on crizotinib.
      RESULTS: We identified 39 and 196 patients with advanced ROS1- and ALK-positive
      NSCLC, respectively. ROS1-positive patients had significantly lower rates of
      extrathoracic metastases (ROS1 59.0%, ALK 83.2%, P=0.002), including lower rates
      of brain metastases (ROS1 19.4%, ALK 39.1%; P = 0.033), at initial metastatic
      diagnosis. Despite similar overall survival between ALK- and ROS1-positive
      patients treated with crizotinib (median 3.0 versus 2.5 years, respectively;
      P=0.786), ROS1-positive patients also had a significantly lower cumulative
      incidence of brain metastases (34% vs. 73% at 5 years; P<0.0001). Additionally,
      we identified 16 patients who underwent a total of 17 repeat biopsies following
      progression on crizotinib. ROS1 resistance mutations were identified in 53% of
      specimens, including 9/14 (64%) non-brain metastasis specimens. ROS1 mutations
      included: G2032R (41%), D2033N (6%), and S1986F (6%). CONCLUSIONS: Compared to
      ALK rearrangements, ROS1 rearrangements are associated with lower rates of
      extrathoracic metastases, including fewer brain metastases, at initial metastatic
      diagnosis. ROS1 resistance mutations, particularly G2032R, appear to be the
      predominant mechanism of resistance to crizotinib, underscoring the need to
      develop novel ROS1 inhibitors with activity against these resistant mutants.

PMID- 29333530
TI  - Transparent Flexible Active Faraday Cage Enables In Vivo Capacitance Measurement
      in Assembled Microsensor.
AB  - Capacitive micro-sensors such as accelerometers, gyroscopes and pressure sensors
      are increasingly used in the modern electronic world. However, the in vivo use of
      capacitive sensing for measurement of pressure or other variables inside a human
      body suffers from significant errors due to stray capacitance. This paper
      proposes a solution consisting of a transparent thin flexible Faraday cage that
      surrounds the sensor. By supplying the active sensing voltage simultaneously to
      the deformable electrode of the capacitive sensor and to the Faraday cage, the
      stray capacitance during in vivo measurements can be largely eliminated. Due to
      the transparency of the Faraday cage, the top and bottom portions of a capacitive
      sensor can be accurately aligned and assembled together. Experimental results
      presented in the paper show that stray capacitance is reduced by a factor of 10
      by the Faraday cage, when the sensor is subjected to a full immersion in water.

PMID- 29333533
TI  - Psychosocial Outcomes Among Children Following Defilement And The Caregivers
      Responses To The Children's Trauma: A Qualitative Study From Nairobi Suburbs,
      Kenya.
AB  - Defilement is traumatic and often associated with psychosocial problems in
      children, parental distress and significant social strain on family relationships
      and well-being. This study aimed at examining psychosocial outcomes in defiled
      children and their caregivers' perceptions of the children's trauma after
      defilement. The study was carried out between June 2015 and July 2016 at Kenyatta
      National Hospital and Nairobi Women's Hospital. It adopted a qualitative
      descriptive design using interviews to obtain information from six purposely
      selected caregivers comprising of four mothers, one father and one grandmother.
      All the perpetrators were adult males and two of the defiled children were male
      and 5 were female. Two of the children were siblings; a brother and his sister.
      Five of the perpetrators were known to the children and one of these was the
      child's biological father. The defiled children had negative outcomes in terms of
      poor academic performance, low self esteem, depression and poor social
      relationships. In addition one of the children contracted HIV/AIDS, two became
      pregnant, one was used to traffic drugs, and another had mental retardation. The
      caregivers felt significant psychosocial distress. There is therefore, need to
      routinely screen for psychological, social and physical outcomes of children
      exposed to defilement trauma and to always consider caregiver distress when
      treating these children.

PMID- 29333531
TI  - Patient-Reported Outcome Measures (PROM) as A Preoperative Assessment Tool.
AB  - Aim of review: Patient-reported outcomes (PRO) on functional, social, and
      behavioral factors might be important preoperative predictors of postoperative
      outcomes. We conducted a literature review to explore associations of
      preoperative depression, socioeconomic status, social support, functional
      status/frailty, cognitive status, self-management skills, health literacy, and
      nutritional status with surgical outcomes. Methods: Two electronic data bases,
      including PubMed and Google Scholar, were searched linking either depression,
      socioeconomic status, social support, functional status/frailty, cognitive
      status, self-management skills, health literacy, or nutritional status with
      surgery, postoperative complications, or perioperative period within the past 2
      decades. Recent findings: Preoperative depression has been linked to
      postoperative delirium, complications, persistent pain, longer lengths of stay,
      and mortality. Socioeconomic status associates with overall and cancer-free
      survival. Low socioeconomic status has also been connected to medication non-
      compliance. Social support can predict overall and cancer- free survival, as well
      as physical, social and emotional quality of life. Poor functional status and
      frailty have been related to postoperative complications, longer lengths of stay,
      post-discharge institutionalization, and higher costs. Preoperative cognitive
      impairment also associates with self-medication management errors, postoperative
      cognitive impairment, delirium, complications and mortality. In addition, a
      greater tendency for reduced adherence to preoperative medication instructions
      has been linked to health illiteracy. Preoperative malnutrition is prevalent and
      associates with postoperative morbidity. Conclusion: Efficient and effective
      assessments of social and behavioral determinants of health, functional status,
      health literacy, patient's perception of health, and preferences for self
      management may improve postoperative management and surgical outcomes,
      particularly among vulnerable patients undergoing elective surgery who might have
      subtle physical, social, or psychological deficits or challenges, otherwise
      missed upon routine evaluation. Patient Reported Outcome Measures (PROMs) can be
      used to effectively and efficiently collect these factors in the preoperative
      period, thereby identifying areas that can be intervened preemptively. (Partially
      Funded by the National Institute on Aging and the Wake Forest University Claude
      D. Pepper Older Americans Independence Center.).

PMID- 29333535
TI  - It is Time to Obligate the Warning Messages on Junk Food Packages and
      Advertisements: A Step to live long.

PMID- 29333534
TI  - The Stagnant Adaptation of Defined and Xeno-Free Culture of iPSCs in Academia.
AB  - Pluripotent Stem Cells were originally derived and cultured using a feeder layer
      of cells. Movements have been undertaken to transition from this method to one
      more defined, high-throughput, and without xenogenic factors. Tremendous research
      has been done in this area and many products have been developed, however, based
      on our analysis of recent publications in stem cell related journals many in
      academia are still using older methods like a feeder layer. In this short
      communication, we discuss the feasibility of transitioning to defined, xeno-free
      methods, how a standardized method could improve the field and industry, and that
      a study bringing together multiple institutions comparing culture methods could
      be done to evaluate the efficacy of these new methods.

PMID- 29333532
TI  - Molecular Docking: From Lock and Key to Combination Lock.
AB  - Accurate modeling of protein ligand binding is an important step in structure
      based drug design, is a useful starting point for finding new lead compounds or
      drug candidates. The 'Lock and Key' concept of protein-ligand binding has
      dominated descriptions of these interactions, and has been effectively translated
      to computational molecular docking approaches. In turn, molecular docking can
      reveal key elements in protein-ligand interactions-thereby enabling design of
      potent small molecule inhibitors directed against specific targets. However,
      accurate predictions of binding pose and energetic remain challenging problems.
      The last decade has witnessed more sophisticated molecular docking approaches to
      modeling protein-ligand binding and energetics. However, the complexities that
      confront accurate modeling of binding phenomena remain formidable. Subtle
      recognition and discrimination patterns governed by three-dimensional features
      and microenvironments of the active site play vital roles in consolidating the
      key intermolecular interactions that mediates ligand binding. Herein, we briefly
      review contemporary approaches and suggest that future approaches treat protein
      ligand docking problems in the context of a 'combination lock' system.

PMID- 29333538
TI  - Editorial: What's next after "universal" adhesives, "bioactive" adhesives?

PMID- 29333536
TI  - OCT-Angiography for Non-Invasive Monitoring of Neuronal and Vascular Structure in
      Mouse Retina: Implication for Characterization of Retinal Neurovascular Coupling.
AB  - Purpose: Optical coherence tomography angiography (OCT-A) is a newly developed
      technique to visualize retinal vasculature non-invasively based on
      interferometry. Although OCT-A has been used clinically, its applications in
      small animal studies have been limited. This study is designed to develop and
      demonstrate the feasibility of a protocol for the use of an en-face OCT-based
      method to visualize and quantify retinal microvasculature in mice that can be
      used for in vivo assessment of retina ischemia. Methods: A customized algorithm
      was developed to extract angiographic profiles of the mouse retina from en-face
      OCT using an unmodified Bioptigen Envisu R-Class OCT imaging system. En-face OCT
      images were collected in living animals and then compared to images acquired
      following termination of blood flow to the retina. The images were processed with
      ImageJ using the raw file importer. The vessel enhancement algorithm was
      developed based on a combination of local contrast enhancement, Laplacian of
      Gaussian peak detection and background subtraction methods. For comparison,
      fluorescein angiography (FA) was performed using Heidelberg Spectralis(r) HRA+OCT
      imaging system. Results: By vessel enhancement algorithm, we successfully
      extracted retinal vasculature and quantified retinal vessel branch points,
      vascular area and vessel lengths with AngioTool. While the retinal neuronal
      structure could be simultaneously identified and quantified using B-scan and
      volumetric OCT run in the annular scanning model, the retinal vasculature in OCT
      A was dramatically diminished after the animals were sacrificed, indicating en
      face OCT-A signal is a measure of the blood flow. Conclusions: These studies
      indicate that a novel approach to extract angiographs from en-face OCT images by
      utilizing local structure enhancement can be used to provide depth-resolved
      retinal vasculature distributions. Simultaneous non-invasive analysis of retinal
      vessels and neurons by OCT-A and OCT may provide a novel approach to characterize
      retinal ischemia accompanied by neurovascular coupling.

PMID- 29333539
TI  - Past, present, and future of the IAAD.

PMID- 29333542
TI  - Acceleration of bursty multiprotein target search kinetics on DNA by
      colocalisation.
AB  - Proteins are capable of locating specific targets on DNA by employing a
      facilitated diffusion process with intermittent 1D and 3D search steps. Gene
      colocalisation and coregulation-i.e. the spatial proximity of two communicating
      genes-is one factor capable of accelerating the target search process along the
      DNA. We perform Monte Carlo computer simulations and demonstrate the benefits of
      gene colocalisation for minimising the search time in a model DNA-protein system.
      We use a simple diffusion model to mimic the search for targets by proteins,
      produced initially in bursts of multiple proteins and performing the first
      passage search on the DNA chain. The behaviour of the mean first-passage times to
      the target is studied as a function of distance between the initial position of
      proteins and the DNA target position, as well as versus the concentration of
      proteins. We also examine the properties of bursty target search kinetics for
      varying physical-chemical protein-DNA binding affinity. Our findings underline
      the relevance of colocalisation of production and binding sites for protein
      search inside biological cells.

PMID- 29333543
TI  - In vitro evaluation of the enantiomeric R- and S-1,1'-binaphthyl-2,2'
      diaminodichlorido-Pt(ii) complexes in human Burkitt lymphoma cells: emphasis on
      cellular accumulation, cytotoxicity, DNA binding, and ability to induce
      apoptosis.
AB  - The aim of this project is to gain insights into the uptake and cellular actions
      of the enantiomeric R- and S-1,1'-binaphthyl-2,2'-diaminodichlorido-Pt(ii)
      complexes (R- and S-[Pt(DABN)Cl2]) in the cisplatin-sensitive human Burkitt
      lymphoma cell line (Gumbus, IC50: 1.3 +/- 0.2 MUM) and its cisplatin-resistant
      sub-line (CDDPrGB, IC50: 6.6 +/- 1.2 MUM). The cellular uptakes of R- and S
      [Pt(DABN)Cl2] are ca. 4-fold higher than cisplatin, and involve a transport
      mechanism independent of the volume-sensitive, organic anion-channel complex,
      which facilitates cisplatin accumulation. The cisplatin-resistant CDDPrGB cells
      are not cross-resistant to either S- or R-[Pt(DABN)Cl2]. We also find that even
      though R-[Pt(DABN)Cl2] has a higher maximal cellular uptake and binds at higher
      levels to calf-thymus DNA than S-[Pt(DABN)Cl2], it appears that S-[Pt(DABN)Cl2]
      is more cytotoxic for Gumbus (IC50: 0.4 +/- 0.1 MUM) compared to R-[Pt(DABN)Cl2]
      (IC50: 0.7 +/- 0.3 MUM). The cellular action of R- and S-[Pt(DABN)Cl2] involves
      G0/G1 cell cycle arrest and cell death involving the extrinsic and intrinsic
      apoptotic pathways.

PMID- 29333537
TI  - Cerebral Autoregulation in Hypertension and Ischemic Stroke: A Mini Review.
AB  - Aging and chronic hypertension are associated with dysfunction in vascular smooth
      muscle, endothelial cells, and neurovascular coupling. These dysfunctions induce
      impaired myogenic response and cerebral autoregulation, which diminish the
      protection of cerebral arterioles to the cerebral microcirculation from elevated
      pressure in hypertension. Chronic hypertension promotes cerebral focal ischemia
      in response to reductions in blood pressure that are often seen in sedentary
      elderly patients on antihypertensive therapy. Cerebral autoregulatory dysfunction
      evokes Blood-Brain Barrier (BBB) leakage, allowing the circulating inflammatory
      factors to infiltrate the brain to activate glia. The impaired cerebral
      autoregulation-induced inflammatory and ischemic injury could cause neuronal cell
      death and synaptic dysfunction which promote cognitive deficits. In this brief
      review, we summarize the pathogenesis and signaling mechanisms of cerebral
      autoregulation in hypertension and ischemic stroke-induced cognitive deficits,
      and discuss our new targets including 20-Hydroxyeicosatetraenoic acid (20-HETE),
      Gamma-Adducin (Add3) and Matrix Metalloproteinase-9 (MMP-9) that may contribute
      to the altered cerebral vascular function.

PMID- 29333544
TI  - Formal total synthesis of salvianolic acid N.
AB  - An efficient synthetic pathway for the total synthesis of salvianolic acid N has
      been reported. The key reaction steps, the Wittig reaction for Z
      stereoselectivity and an intramolecular cyclization for a seven membered ring
      skeleton, have been optimized to improve the synthetic feasibility and provide
      the best conditions in terms of yield. Moreover, a notable reaction is the
      reaction of the deprotected allylic group with Pd catalyst. An improved overall
      yield of 11% has been achieved for salvianolic acid N starting from 3,4
      dimethoxybenzaldehyde in 11 steps.

PMID- 29333547
TI  - Diverse bimetallic mechanisms emerging from transition metal Lewis acid/base
      pairs: development of co-catalysis with metal carbenes and metal carbonyl anions.
AB  - The rational development of catalytic reactions involving cooperative behavior
      between two catalytic reactive sites represents a frontier area of research from
      which novel reactivity and selectivity patterns emerge. Within this context, this
      Feature highlights the development of a cooperative system involving transition
      metal Lewis acid/base pairs. Bimetallic systems consisting of copper carbene
      Lewis acids and metal carbonyl anion Lewis bases, (NHC)Cu-[MCO], are easily
      synthesized from readily available organometallic building blocks (NHC = N
      heterocyclic carbene; [MCO]- = metal carbonyl anion, e.g. [FeCp(CO)2]-, [Mn(CO)5]
      , etc.). Stoichiometric reactivity studies indicate that the dative Cu<-M bonds
      in these systems are labile towards heterolysis under mild conditions, thus
      providing in situ access both to polar metal-metal bonds and to "frustrated"
      transition metal Lewis acid/base pairs as dictated by reaction conditions.
      Catalytic transformations ranging from C-C and C-B coupling reactions to
      hydrogenation and other reductions have been developed from both manifolds:
      bimetallic catalysis involving (a) binuclear intermediates engaging in
      cooperative bond activation and formation, and (b) orthogonal mononuclear
      intermediates that operate in either tandem or co-dependent manners. Preliminary
      indications point to the future emergence of novel reactivity and selectivity
      patterns as these new motifs undergo continued development, and additionally
      demonstrate that the relative matching of two reactive sites provides a method
      for controlling catalytic behavior. Collectively, these results highlight the
      fundamental importance of exploring unconventional catalytic paradigms.

PMID- 29333548
TI  - Efficient generation of an oxidopyrylium ylide using a Pd catalyst and its [5+2]
      cycloadditions with several dipolarophiles.
AB  - An efficient method for the generation of an oxidopyrylium ylide from 6-acetoxy-6
      acetoxymethyl-2H-pyran-3(6H)-one using a Pd catalyst and [5+2] cycloadditions of
      the resulting ylide are described. Among substituted styrene derivatives as
      dipolarophiles, electron-rich styrenes showed higher yield (up to 80%). The [5+2]
      cycloaddition reactions can also be applied to exo-methylene cyclic compounds,
      and an improved method for the synthesis of polygalolide intermediate has been
      demonstrated.

PMID- 29333550
TI  - CuWO4 as a photocatalyst for room temperature aerobic benzylamine oxidation.
AB  - The aerobic photochemical oxidation of benzylamine was carried out on the ternary
      oxides CuWO4 and BiVO4 as a test proton-coupled-electron-transfer reaction in
      acetonitrile. Both oxides give the coupled imine product, N
      benzylidenebenzylamine, in near quantitative (98-99%) yield, with rate constants
      of 0.34 h-1 g-1 and 0.70 h-1 g-1 for CuWO4 and BiVO4, respectively.

PMID- 29333551
TI  - Anharmonic vibrational spectra from double incremental potential energy and
      dipole surfaces.
AB  - We extend the fragmentation-based double incremental expansion in FALCON
      coordinates (DIF) and its linear-scaling analogue [C. Konig and O. Christiansen,
      J. Chem. Phys., 2016, 145, 064105] to dipole surfaces. Thereby, we enable the
      calculation of intensities in vibrational absorption spectra from these cost
      efficient property surfaces. We validate the obtained potential energy and dipole
      surfaces by vibrational spectra calculations employing damped response theory for
      correlated vibrational coupled cluster wave functions. Our largest calculation on
      a hexa-phenyl includes all 180 vibrational degrees of freedom of the system,
      which illustrates the potential of both the DIF schemes for property surface
      generation and the use of damped response theory from high-dimensional correlated
      vibrational wave functions. Generally, we obtain good agreement between the
      spectra calculated from the DIF property surfaces and the non-fragmented
      analogues. Moreover, when adopting suitable electronic structure methods, good
      agreement with respect to the experiment can be obtained, as shown for the
      example of 5-methylfurfural and RI-MP2. In conclusion, our results illustrate
      that the presented scheme with linearly scaling surfaces enables high quality
      spectra, as long as reasonably sized fragments can be defined. With this work, we
      push the realistic limits of vibrational spectra calculations from vibrational
      wave function methods and accurate electronic structure calculations to
      significantly larger systems than currently accessible.

PMID- 29333545
TI  - Dynamic changes in copper homeostasis and post-transcriptional regulation of
      Atp7a during myogenic differentiation.
AB  - Copper (Cu) is an essential metal required for activity of a number of redox
      active enzymes that participate in critical cellular pathways such as metabolism
      and cell signaling. Because it is also a toxic metal, Cu must be tightly
      controlled by a series of transporters and chaperone proteins that regulate Cu
      homeostasis. The critical nature of Cu is highlighted by the fact that mutations
      in Cu homeostasis genes cause pathologic conditions such as Menkes and Wilson
      diseases. While Cu homeostasis in highly affected tissues like the liver and
      brain is well understood, no study has probed the role of Cu in development of
      skeletal muscle, another tissue that often shows pathology in these conditions.
      Here, we found an increase in whole cell Cu content during differentiation of
      cultured immortalized or primary myoblasts derived from mouse satellite cells. We
      demonstrate that Cu is required for both proliferation and differentiation of
      primary myoblasts. We also show that a key Cu homeostasis gene, Atp7a, undergoes
      dynamic changes in expression during myogenic differentiation. Alternative
      polyadenylation and stability of Atp7a mRNA fluctuates with differentiation stage
      of the myoblasts, indicating post-transcriptional regulation of Atp7a that
      depends on the differentiation state. This is the first report of a requirement
      for Cu during myogenic differentiation and provides the basis for understanding
      the network of Cu transport associated with myogenesis.

PMID- 29333552
TI  - Counting DNA molecules with visual segment-based readouts in minutes.
AB  - An ultrafast and extremely simple approach was proposed to count the number of
      DNA molecules without any microfluidic-based device. By directly counting the
      number of amplicon clusters in a capillary, the absolute amount of DNA molecules
      could be easily determined.

PMID- 29333553
TI  - Microwave-assisted synthesis of TEMPO-labeled hydrogels traceable with MRI.
AB  - Polymer functionalization strategies have recently attracted considerable
      attention for several applications in biomaterials science. In particular,
      technological advancements in medical imaging have focused on the design of
      polymeric matrices to improve non-invasive approaches and diagnostic accuracy. In
      this scenario, the use of microwave irradiation of aqueous solutions containing
      appropriate combinations of polymers is gaining increasing interest in the
      synthesis of sterile hydrogels without using monomers, eliminating the need to
      remove unreacted species. In this study, we developed a method for the in situ
      fabrication of TEMPO-labeled hydrogels based on a one-pot microwave reaction that
      can then be tracked by magnetic resonance imaging (MRI) without using toxic
      compounds that could be hostile for the target tissue. Click chemistry was used
      to link TEMPO to the polymeric scaffold. In an in vivo model, the system was able
      to preserve its TEMPO paramagnetic activity up to 1 month after hydrogel
      injection, showing a clear detectable signal on T1-weighted MRI with a
      longitudinal relaxivity value of 0.29 mM s-1, comparable to a value of 0.31 mM s
      1 characteristic of TEMPO application. The uncleavable conjugation between the
      contrast agent and the polymeric scaffold is a leading point to record these
      results: the use of TEMPO only physically entrapped in the polymeric scaffold did
      not show MRI traceability even after few hours. Moreover, the use of TEMPO
      labeled hydrogels can also help to reduce the number of animals sacrificed being
      a longitudinal non-invasive technique.

PMID- 29333554
TI  - In-cell NMR: from metabolites to macromolecules.
AB  - In-cell NMR of macromolecules has gained momentum over the last ten years as an
      approach that might bridge the branches of cell biology and structural biology.
      In this review, we put it in the context of earlier efforts that aimed to
      characterize by NMR the cellular environment of live cells and their
      intracellular metabolites. Although technical aspects distinguish these earlier
      in vivo NMR studies and the more recent in cell NMR efforts to characterize
      macromolecules in a cellular environment, we believe that both share major
      concerns ranging from sensitivity and line broadening to cell viability.
      Approaches to overcome the limitations in one subfield thereby can serve the
      other one and vice versa. The relevance in biomedical sciences might stretch from
      the direct following of drug metabolism in the cell to the observation of target
      binding, and thereby encompasses in-cell NMR both of metabolites and
      macromolecules. We underline the efforts of the field to move to novel biological
      insights by some selected examples.

PMID- 29333555
TI  - A mechanism study on the hydrogen evolution reaction catalyzed by molybdenum
      disulfide complexes.
AB  - Density functional theory (DFT) calculations show that H2 evolution is attributed
      to active sulfur hydrides derived from MoS2 complexes via two- or three-electron
      reduction from the synthesized [(PY5Me2)MoS2]2+. Water acts as a bridge for H2
      evolution from the intermolecular H+/H- coupling between sulfur hydride complexes
      and hydrated protons.

PMID- 29333556
TI  - Correction: Chemical analysis in saliva and the search for salivary biomarkers -
      a tutorial review.
AB  - Correction for 'Chemical analysis in saliva and the search for salivary
      biomarkers - a tutorial review' by Kamonwad Ngamchuea, et al., Analyst, 2018,
      143, 81-99.

PMID- 29333557
TI  - Drop impact dynamics on slippery liquid-infused porous surfaces: influence of oil
      thickness.
AB  - Slippery liquid-infused porous surfaces (SLIPS) are porous nanostructures
      impregnated with a low surface tension lubricant. They have recently shown great
      promise in various applications that require non-wettable superhydrophobic
      surfaces. In this paper, we investigate experimentally the influence of the oil
      thickness on the wetting properties and drop impact dynamics of new SLIPS. By
      tuning the thickness of the oil layer deposited through spin-coating, we show
      that a sufficiently thick layer of oil is necessary to avoid dewetting spots on
      the porous nanostructure and thus increasing the homogeneity of the liquid
      distribution. Drop impact on these surfaces is investigated with a particular
      emphasis on the spreading and rebound dynamics when varying the oil thickness and
      the Weber number.

PMID- 29333558
TI  - Selective hydrogenation of nitroarenes using an electrogenerated polyoxometalate
      redox mediator.
AB  - The 2-electron reduced form of the polyoxometalate silicotungstic acid
      (H4[SiW12O4]) is shown to be an effective and selective hydrogenation agent for a
      range of nitroarenes without the need for any co-catalyst. The ease of generation
      of the active species and its recyclability suggest that a new approach to this
      important class of chemical conversions is possible.

PMID- 29333560
TI  - A design of experiment approach for efficient multi-parametric drug testing using
      a Caenorhabditis elegans model.
AB  - When studying the drug effectiveness towards a target model, one should
      distinguish the effects of the drug itself and of all the other factors that
      could influence the screening outcome. This comprehensive knowledge is crucial,
      especially when model organisms are used to study the drug effect at a systemic
      level, as a higher number of factors can influence the drug-testing outcome.
      Covering the entire experimental domain and studying the effect of the
      simultaneous change in several factors would require numerous experiments, which
      are costly and time-consuming. Therefore, a design of experiment (DoE) approach
      in drug-testing is emerging as a robust and efficient method to reduce the use of
      resources, while maximizing the knowledge of the process. Here, we used a 3
      factor-Doehlert DoE to characterize the concentration-dependent effect of the
      drug doxycycline on the development duration of the nematode Caenorhabditis
      elegans. To cover the experimental space, 13 experiments were designed and
      performed, where different doxycycline concentrations were tested, while also
      varying the temperature and the food amount, which are known to influence the
      duration of C. elegans development. A microfluidic platform was designed to
      isolate and culture C. elegans larvae, while testing the doxycycline effect with
      full control of temperature and feeding over the entire development. Our approach
      allowed predicting the doxycycline effect on C. elegans development in the
      complete drug concentration/temperature/feeding experimental space, maximizing
      the understanding of the effect of this antibiotic on the C. elegans development
      and paving the way towards a standardized and optimized drug-testing process.

PMID- 29333559
TI  - Oxidation of a [Cu2S] complex by N2O and CO2: insights into a role of
      tetranuclearity in the CuZ site of nitrous oxide reductase.
AB  - Oxidation of a [Cu2(MU-S)] complex by N2O or CO2 generated a [Cu2(MU-SO4)]
      product. In the presence of a sulfur trap, a [Cu2(MU-O)] species also formed from
      N2O. A [Cu2(MU-CS3)] species derived from CS2 modeled initial reaction
      intermediates. These observations indicate that one role of tetranuclearity in
      the CuZ catalytic site of nitrous oxide reductase is to protect the crucial S2-
      ligand from oxidation.

PMID- 29333561
TI  - Pharmacokinetics of the B-Cell Lymphoma 2 (Bcl-2) Inhibitor Venetoclax in Female
      Subjects with Systemic Lupus Erythematosus.
AB  - BACKGROUND AND OBJECTIVE: Venetoclax is an oral selective Bcl-2 inhibitor
      approved for the treatment of patients with chronic lymphocytic leukemia with 17p
      deletion. Mechanistic and preclinical evidence warranted evaluation of venetoclax
      for the treatment of systemic lupus erythematosus (SLE). This work characterized
      the pharmacokinetics of venetoclax in female subjects with SLE. METHODS: Single
      (10-500 mg) and multiple (30-600 mg) escalating doses of venetoclax or matching
      placebo were evaluated using randomized, double-blind, placebo-controlled designs
      (6 active and 2 placebo per dose with 73 unique SLE patients enrolled, 25 of whom
      enrolled twice). The multiple-dose evaluation consisted of two cycles, each with
      once-daily dosing for 7 days followed by a 21-day washout. Non-compartmental and
      population pharmacokinetic analyses of venetoclax serial plasma concentrations
      were conducted. RESULTS: Venetoclax exhibited approximately dose-proportional
      exposures, with peak concentrations observed 4-8 h post-dose. Venetoclax steady
      state exposures were achieved by day 4 of dosing, and the median area under the
      plasma concentration-time curve (AUC) accumulation ratio ranged from 1.1 to 1.5.
      A two-compartment model with first-order absorption and elimination described
      venetoclax pharmacokinetics. The estimates (95% bootstrap confidence interval)
      for venetoclax apparent clearance, central and peripheral volumes of
      distribution, intercompartmental clearance, absorption rate constant, and lag
      time were 16.3 L/h (14.6-17.9), 37 L (26-57), 122 L (98-183), 3.7 L/h (2.6-5.0),
      0.13 h-1 (0.11-0.17), and 1.6 h (1.6-1.7), respectively. The population estimate
      for venetoclax terminal-phase elimination half-life was approximately 28 h.
      CONCLUSIONS: In female subjects with SLE, venetoclax displayed pharmacokinetic
      characteristics consistent with previous observations in subjects with
      hematologic malignancies. CLINICALTRIALS. GOV IDENTIFIER: NCT01686555.

PMID- 29333562
TI  - Have You Ever Googled a Patient or Been Friended by a Patient? Social Media
      Intersects the Practice of Genetic Counseling.
AB  - Patients and healthcare providers are becoming increasingly connected via social
      media, bringing new opportunities and challenges. Direct connection can occur
      between patients and providers using online tools such as Facebook and LinkedIn.
      In addition, providers can gather information about patients using a search
      engine such as Google, referred to as patient-targeted Googling (PTG). An online
      54-item survey was used to gain information on (1) how and to what extent genetic
      counseling students and genetic counselors connect directly with patients via
      social media sites, and (2) gather information on providers using PTG. Four
      hundred genetic counseling students and genetic counselors participated in the
      survey. The majority of respondents (88.9%; n = 344/387) find it is never or
      rarely acceptable to interact with current patients via social media sites;
      however, 27.7% (n = 110/397) have visited a patient's social media site.
      Gathering information for patient care was the most commonly reported reason
      (76.8%; n = 43/56). Thirty-three percent (n = 130/394) have considered searching
      online or actually searched online for information about a patient. Curiosity was
      the most common reason (92.7%; n = 114/123); although, respondents also used PTG
      to obtain contact information and to prepare for patient sessions. Our study
      supports the need for development and dissemination of professional guidelines to
      serve as a valuable resource for practicing genetic counselors and genetic
      counseling training programs.

PMID- 29333563
TI  - Aldehyde Dehydrogenase Activity in Adipose Tissue: Isolation and Gene Expression
      Profile of Distinct Sub-population of Mesenchymal Stromal Cells.
AB  - Thanks to their relative abundance and easier collection, adipose tissue (AT) is
      considered an alternative source for the isolation of mesenchymal stromal cells
      (MSCs). MSCs have great therapeutic values and are thus under investigations for
      several clinical indications such as regenerative medicine and immunomodulation.
      In this work, we aimed to identify, isolate and characterize AT-MSCs based on
      their aldehyde dehydrogenase (ALDH) activity known to be a classical feature of
      stem cells. FACS technology allowed to isolate two different populations of AT
      MSCs according to their ALDH activity (referred as ALDH+ and ALDH-). Depending on
      their ALDH activity, the transcriptome analysis of both cell populations
      demonstrated a differential pattern of genes related to the main properties of
      MSCs (proliferation, response to hypoxia, angiogenesis, phenotype, stemness,
      multilineage, hematopoiesis, immunomodulation). Based on these profiling, both AT
      MSC populations could differ in terms of biological responses and
      functionalities. Collectively, the use of ALDH for isolating and identifying sub
      populations of MSCs with specific gene profile may represent an alternative
      method to provide solutions for targeted therapeutic applications.

PMID- 29333564
TI  - Is 123I-metaiodobenzylguanidine heart-to-mediastinum ratio dependent on age? From
      Japanese Society of Nuclear Medicine normal database.
AB  - BACKGROUND: Heart-to-mediastinum ratios (HMRs) of 123I-metaiodobenzylguanidine
      (MIBG) have usually been applied to prognostic evaluations of heart failure and
      Lewy body disease. However, whether these ratios depend on patient age has not
      yet been clarified using normal databases. METHODS: We analyzed 62 patients
      (average age 57 +/- 19 years, male 45%) derived from a normal database of the
      Japanese Society of Nuclear Medicine working group. The HMR was calculated from
      early (15 min) and delayed (3-4 h) anterior planar 123I-MIBG images. All HMRs
      were standardized to medium-energy general purpose (MEGP) collimator equivalent
      conditions using conversion coefficients for the collimator types. Washout rates
      (WR) were also calculated, and we analyzed whether early and late HMR, and WR are
      associated with age. RESULTS: Before standardization of HMR to MEGP collimator
      conditions, HMR and age did not significantly correlate. However, late HMR
      significantly correlated with age after standardization: late HMR = - 0.0071 *
      age + 3.69 (r2 = 0.078, p = 0.028), indicating that a 14-year increase in age
      corresponded to a decrease in HMR of 0.1. Whereas the lower limit (2.5% quantile)
      of late HMR was 2.3 for all patients, it was 2.5 and 2.0 for those aged <= 63 and
      > 63 years, respectively. Early HMR tended to be lower in subjects with the
      higher age (p = 0.076), whereas WR was not affected by age. CONCLUSION: While
      late HMR was slightly decreased in elderly patients, the lower limit of 2.2-2.3
      can still be used to determine both early and late HMR.

PMID- 29333566
TI  - Principles of Management of Central Nervous System Infections.
AB  - CNS infections in children are medical emergency and are associated with high
      mortality and morbidity. For diagnosis, a high index of suspicion is required.
      Clinical assessment should be supplemented by laboratory investigations including
      CSF Gram stain and cultures, blood culture, PCR on CSF, serological tests, and
      imaging. Commonly associated life threatening complications include coma,
      seizure, raised intracranial pressure (ICP), focal deficits, shock, respiratory
      failure, and fluid and electrolyte abnormalities. Immediate management should
      first address control of airway, breathing and circulation; protocolized
      management of raised ICP and status epilepticus; maintaining adequate
      intravascular volume; and close monitoring for early detection of complications.
      Appropriate antimicrobial agents should be administered promptly according to the
      suspected pathogen. Clinical evaluation, laboratory workup, specific
      antimicrobial therapy, supportive treatment, and management of associated
      complications should go hand in hand in a protocolized way for better outcome.

PMID- 29333565
TI  - Manual on the proper use of lutetium-177-labeled somatostatin analogue (Lu-177
      DOTA-TATE) injectable in radionuclide therapy (2nd ed.).
AB  - Here we present the guideline for the treatment of neuroendocrine tumors using Lu
      177-DOTA-TATE on the basis of radiation safety aspects in Japan. This guideline
      was prepared by a study supported by Ministry of Health, Labour, and Welfare, and
      approved by Japanese Society of Nuclear Medicine. Lu-177-DOTA-TATE treatment in
      Japan should be carried out according to this guideline. Although this guideline
      is applied in Japan, the issues for radiation protection shown in this guideline
      are considered internationally useful as well. Only the original Japanese version
      is the formal document.

PMID- 29333567
TI  - Predictors for Intracranial Hemorrhage Following Intravenous Thrombolysis in
      Posterior Circulation Stroke.
AB  - Intravenous thrombolysis (IVT) is a standard treatment for anterior (ACS) and
      posterior circulation stroke (PCS). However, due to the low occurrence of PCS and
      of intracranial hemorrhage (ICH) in PCS, the knowledge about ICH predictors
      following IVT in PCS is sparse. Our aim was to identify predictors for ICH
      following IVT in PCS. The set consisted of 1281 consecutive ischemic stroke (IS)
      patients treated with IVT, out of which 158 (103 males; mean age 65.6 +/- 12.3
      years) had PCS. Collected data include baseline characteristics, common stroke
      risk factors, pre-medication, stroke severity, admission blood glucose level,
      blood pressure and treatment with intravenous antihypertensive therapy before and
      during IVT, occlusion of arteries, recanalization rate, time to treatment, and
      clinical outcome at day 90. Overall, 11 (7%) patients had ICH. Atrial
      fibrillation (p = 0.004), neurological deficit at time of treatment in the
      National Institutes of Health Stroke Scale (p = 0.016), decreased level of
      consciousness (p = 0.003), occlusion of basilar artery (p = 0.007), occlusion of
      PCA (p = 0.001), and additional endovascular therapy (p = 0.001) were identified
      by logistic regression analysis as significant predictors for ICH in PCS.
      Patients with ischemic lesion in the brainstem, occlusion of vertebral artery, or
      absence of basilar and posterior cerebral artery occlusion might be considered
      for treatment with IVT even in borderline cases. Those patients seem to have less
      frequently favorable outcomes without an increase in ICH rate. Time to IVT in PCS
      seems not to influence ICH risk or chances for favorable outcomes as
      significantly as it does in ACS.

PMID- 29333569
TI  - An integrated fuzzy-based advanced eutrophication simulation model to develop the
      best management scenarios for a river basin.
AB  - Assessment of water quality status of a river with respect to its discharge has
      become prerequisite to sustainable river basin management. The present paper
      develops an integrated model for simulating and evaluating strategies for water
      quality management in a river basin management by controlling point source
      pollutant loadings and operations of multi-purpose projects. Water Quality
      Analysis and Simulation Program (WASP version 8.0) has been used for modeling the
      transport of pollutant loadings and their impact on water quality in the river.
      The study presents a novel approach of integrating fuzzy set theory with an
      "advanced eutrophication" model to simulate the transmission and distribution of
      several interrelated water quality variables and their bio-physiochemical
      processes in an effective manner in the Ganges river basin, India. After
      calibration, simulated values are compared with the observed values to validate
      the model's robustness. Fuzzy technique of order preference by similarity to
      ideal solution (F-TOPSIS) has been used to incorporate the uncertainty associated
      with the water quality simulation results. The model also simulates five
      different scenarios for pollution reduction, to determine the maximum pollutant
      loadings during monsoon and dry periods. The final results clearly indicate how
      modeled reduction in the rate of wastewater discharge has reduced impacts of
      pollutants in the downstream. Scenarios suggesting a river discharge rate of 1500
      m3/s during the lean period, in addition to 25 and 50% reduction in the load
      rate, are found to be the most effective option to restore quality of river
      Ganges. Thus, the model serves as an important hydrologic tool to the policy
      makers by suggesting appropriate remediation action plans.

PMID- 29333568
TI  - Comparison of effects of thawing entire donor sperm vial vs. partial thawing
      (shaving) on sperm quality.
AB  - PURPOSE: Partial thawing of a vial of cryopreserved sperm (shaving) is sometimes
      applied as a measure to preserve sperm for further use, particularly in cases of
      very restricted sperm quantity. However, mechanical violence may disrupt the
      sperm-wall and lead to impaired in-vitro fertilization (IVF) outcomes. MATERIAL
      AND METHODS: In a retrospective case-control study at a tertiary, university
      affiliated medical center, we compared the IVF/intracytoplasmic sperm injection
      (ICSI) outcomes of patients who used donor sperm following partial thawing
      (shaving) of the vial of cryopreserved sperm (n = 99) to a control group
      consisting of patients for whom the vial of sperm was completely thawed before
      use (n = 99). RESULTS: While no differences were observed in the rates of oocyte
      fertilization, the mean number of top-quality embryos (TQE) was significantly
      lower in the shaving group than in the complete thawing group (1.33 +/- 0.17 vs.
      1.87 +/- 0.17, p < 0.02). Experimental analysis of aliquots from the same donors
      revealed significantly reduced motility in sperm samples that were shaved vs.
      fully thawed (6.5 vs. 37.1%, p < 0.001). CONCLUSIONS: In cases in which available
      cryopreserved sperm samples are limited, shaving of the vial without thawing can
      be used but with caution and only when absolutely necessary. Further, large
      prospective studies are needed to better clarify whether there is post-thawing
      sperm damage and to compare IVF outcomes after these two thawing methods.

PMID- 29333570
TI  - Professional quality of life, wellness education, and coping strategies among
      emergency physicians.
AB  - Professional quality of life (ProQOL) is affected by and affects professional
      well-being and performance. The objectives of this study are to identify risk
      factors of ProQOL among EM physicians in Zagazig University hospitals (ZUHs), to
      detect the relationship between ProQOL and coping strategies, and to measure the
      implication of the Worksite Wellness Education (WWE) program on improving
      knowledge skills, ProQOL, and coping. An intervention study was conducted among
      108 EM physicians at ZUHs through two stages: assessing ProQOL subscales (CS, BO,
      and STS) and coping strategies and conducting the WWE program. A pre-post-test
      design was used in the evaluation. CS was higher among the older age group,
      smokers, nighttime sleepers, and hobbies' practitioners. Coping strategies
      carried out by EM physicians to overcome stress and their ProQOL scores were
      improved significantly post program. ProQOL has multiple factors that affect it.
      Applying the WWE program will address this concept and may raise awareness about
      how to cope with work stressors.

PMID- 29333571
TI  - Diurnal variations in personal care products in seawater and mussels at three
      Mediterranean coastal sites.
AB  - The presence of personal care products (PCPs) in the marine environment is of
      major concern. PCPs, UV filters, and musks can enter the marine environment
      indirectly through wastewater or directly via recreational activities. We
      conducted this study to document patterns in the occurrence of seven PCPs at
      three coastal sites impacted by recreational activities during 1 day. The study
      focused on diurnal variations in these seven PCPs in seawater and indigenous
      mussels. In seawater, UV filters showed diurnal variations that mirrored
      variations in recreational activities at the sites. Ethylhexyl methoxycinnamate
      (EHMC) and octocrylene (OC) water concentrations increased from under the limit
      of quantification in the morning to 106 and 369 ng/L, respectively, when
      recreational activities were the highest. In mussels, diurnal variations in OC
      were observed, with the lowest concentrations recorded in the morning and then
      increasing throughout the day. As Mytilus spp. are widely used as sentinels in
      coastal pollution monitoring programs (mussel watch), our findings on diurnal
      variations could enhance sampling recommendations for recreational sites impacted
      by PCPs.

PMID- 29333572
TI  - Possible protective effect of the algae spirulina against nephrotoxicity induced
      by cyclosporine A and/or gamma radiation in rats.
AB  - The present study was conducted to evaluate the possible protective role of the
      algae spirulina (Sp) against nephrotoxicity and oxidative stress which are the
      main secondary effects induced by the immunosuppressant drug CSA and/or ionizing
      radiation. In this study, male rats were given Sp (1 g/kg) either for 15 days
      before irradiation (6.5 Gy) or 5 days before and 10 days concomitant with CSA (25
      mg/kg). Markers used to assess renal injury included serum creatinine, urea,
      glucose, albumin, protein, and lipid profile as well as kidney content of reduced
      glutathione (GSH); lipid peroxidation (thiobarbituric acid reactive substances
      (TBARS)); nitrite and superoxide dismutase (SOD) activity. In addition, some
      trace elements (Zn and Mg) were estimated in kidney. Apoptosis was assessed by
      immunohistochemical estimation of caspase-3 expression in addition to
      histopathological examination. Results revealed that gamma radiation and/or CSA
      induced elevation in urea, creatinine, lipids, and glucose while decreasing
      albumin and protein levels. There was a noticeable increase in kidney content of
      GSH, TBARS, and nitrite. Meanwhile, profound decrease in kidney SOD activity was
      observed. Treatment with Sp significantly reversed the changes induced by CSA
      and/or gamma radiation in renal function tests. Spirulina also ameliorated kidney
      oxidative stress through decreasing GSH, TBARS, and nitrite kidney content while
      increasing SOD activity. Histopathological examination further confirmed Sp
      protective efficacy. Moreover, kidney caspase-3 expression that was triggered by
      CSA and/or gamma radiation was decreased. In conclusion, spirulina can be
      regarded as a promising renoprotective natural agent against renal injury induced
      by CSA and/or gamma radiation.

PMID- 29333573
TI  - Simultaneous site-directed mutagenesis of duplicated loci in soybean using a
      single guide RNA.
AB  - KEY MESSAGE: Using a gRNA and Agrobacterium-mediated transformation, we performed
      simultaneous site-directed mutagenesis of two GmPPD loci in soybean. Mutations in
      GmPPD loci were confirmed in at least 33% of T2 seeds. The clustered regularly
      interspaced short palindromic repeat (CRISPR)/CRISPR-associated endonuclease 9
      (Cas9) system is a powerful tool for site-directed mutagenesis in crops. Using a
      single guide RNA (gRNA) and Agrobacterium-mediated transformation, we performed
      simultaneous site-directed mutagenesis of two homoeologous loci in soybean
      (Glycine max), GmPPD1 and GmPPD2, which encode the orthologs of Arabidopsis
      thaliana PEAPOD (PPD). Most of the T1 plants had heterozygous and/or chimeric
      mutations for the targeted loci. The sequencing analysis of T1 and T2 generations
      indicates that putative mutation induced in the T0 plant is transmitted to the T1
      generation. The inheritable mutation induced in the T1 plant was also detected.
      This result indicates that continuous induction of mutations during T1 plant
      development increases the occurrence of mutations in germ cells, which ensures
      the transmission of mutations to the next generation. Simultaneous site-directed
      mutagenesis in both GmPPD loci was confirmed in at least 33% of T2 seeds
      examined. Approximately 19% of double mutants did not contain the Cas9/gRNA
      expression construct. Double mutants with frameshift mutations in both GmPPD1 and
      GmPPD2 had dome-shaped trifoliate leaves, extremely twisted pods, and produced
      few seeds. Taken together, our data indicate that continuous induction of
      mutations in the whole plant and advancing generations of transgenic plants
      enable efficient simultaneous site-directed mutagenesis in duplicated loci in
      soybean.

PMID- 29333574
TI  - Unique metabolic activation of adipose tissue macrophages in obesity promotes
      inflammatory responses.
AB  - AIMS/HYPOTHESIS: Recent studies have identified intracellular metabolism as a
      fundamental determinant of macrophage function. In obesity, proinflammatory
      macrophages accumulate in adipose tissue and trigger chronic low-grade
      inflammation, that promotes the development of systemic insulin resistance, yet
      changes in their intracellular energy metabolism are currently unknown. We
      therefore set out to study metabolic signatures of adipose tissue macrophages
      (ATMs) in lean and obese conditions. METHODS: F4/80-positive ATMs were isolated
      from obese vs lean mice. High-fat feeding of wild-type mice and myeloid-specific
      Hif1alpha-/- mice was used to examine the role of hypoxia-inducible factor-1alpha
      (HIF-1alpha) in ATMs part of obese adipose tissue. In vitro, bone marrow-derived
      macrophages were co-cultured with adipose tissue explants to examine adipose
      tissue-induced changes in macrophage phenotypes. Transcriptome analysis, real
      time flux measurements, ELISA and several other approaches were used to determine
      the metabolic signatures and inflammatory status of macrophages. In addition,
      various metabolic routes were inhibited to determine their relevance for cytokine
      production. RESULTS: Transcriptome analysis and extracellular flux measurements
      of mouse ATMs revealed unique metabolic rewiring in obesity characterised by both
      increased glycolysis and oxidative phosphorylation. Similar metabolic activation
      of CD14+ cells in obese individuals was associated with diabetes outcome. These
      changes were not observed in peritoneal macrophages from obese vs lean mice and
      did not resemble metabolic rewiring in M1-primed macrophages. Instead, metabolic
      activation of macrophages was dose-dependently induced by a set of adipose tissue
      derived factors that could not be reduced to leptin or lactate. Using metabolic
      inhibitors, we identified various metabolic routes, including fatty acid
      oxidation, glycolysis and glutaminolysis, that contributed to cytokine release by
      ATMs in lean adipose tissue. Glycolysis appeared to be the main contributor to
      the proinflammatory trait of macrophages in obese adipose tissue. HIF-1alpha, a
      key regulator of glycolysis, nonetheless appeared to play no critical role in
      proinflammatory activation of ATMs during early stages of obesity.
      CONCLUSIONS/INTERPRETATION: Our results reveal unique metabolic activation of
      ATMs in obesity that promotes inflammatory cytokine release. Further
      understanding of metabolic programming in ATMs will most likely lead to novel
      therapeutic targets to curtail inflammatory responses in obesity. DATA
      AVAILABILITY: Microarray data of ATMs isolated from obese or lean mice have been
      submitted to the Gene Expression Omnibus (accession no. GSE84000).

PMID- 29333575
TI  - A phase 1, dose-escalation study of PF-06664178, an anti-Trop-2/Aur0101 antibody
      drug conjugate in patients with advanced or metastatic solid tumors.
AB  - Purpose and Methods Trop-2 is a glycoprotein over-expressed in many solid tumors
      but at low levels in normal human tissue, providing a potential therapeutic
      target. We conducted a phase 1 dose-finding study of PF-06664178, an antibody
      drug conjugate that targets Trop-2 for the selective delivery of the cytotoxic
      payload Aur0101. The primary objective was to determine the maximum tolerated
      dose and recommended phase 2 dose. Secondary objectives included further
      characterization of the safety profile, pharmacokinetics and antitumor activity.
      Eligible patients were enrolled and received multiple escalating doses of PF
      06664178 in an open-label and unblinded manner based on a modified continual
      reassessment method. Results Thirty-one patients with advanced or metastatic
      solid tumors were treated with escalating doses of PF-06664178 given
      intravenously every 21 days. Doses explored ranged from 0.15 mg/kg to 4.8 mg/kg.
      Seven patients experienced at least one dose limiting toxicity (DLT), either
      neutropenia or rash. Doses of 3.60 mg/kg, 4.2 mg/kg and 4.8 mg/kg were considered
      intolerable due to DLTs in skin rash, mucosa and neutropenia. Best overall
      response was stable disease in 11 patients (37.9%). None of the patients had a
      partial or complete response. Systemic exposure of PF-06664178 increased in a
      dose-related manner. Serum concentrations of free Aur0101 were substantially
      lower than those of PF-06664178 and total antibody. No correlation of Trop-2
      expression and objective response was observed, although Trop-2 overexpression
      was not required for study entry. The intermediate dose of 2.4 mg/kg appeared to
      be the highest tolerated dose, but this was not fully explored as the study was
      terminated early due to excess toxicity. Conclusion PF-06664178 showed toxicity
      at high dose levels with modest antitumor activity. Neutropenia, skin rash and
      mucosal inflammation were dose limiting toxicities. Findings from this study may
      potentially aid in future antibody drug conjugate design and trials.

PMID- 29333576
TI  - Bone radionuclide therapy and increased survival with radium-223 is the way to go
      for nuclear medicine: the offer that oncologists cannot refuse.

PMID- 29333577
TI  - Prostate Cancer Patients' Understanding of the Gleason Scoring System:
      Implications for Shared Decision-Making.
AB  - The Gleason scoring system is a key component of a prostate cancer diagnosis,
      since it indicates disease aggressiveness. It also serves as a risk communication
      tool that facilitates shared treatment decision-making. However, the system is
      highly complex and therefore difficult to communicate: factors which have been
      shown to undermine well-informed and high-quality shared treatment decision
      making. To systematically explore prostate cancer patients' understanding of the
      Gleason scoring system (GSS), we assessed knowledge and perceived importance
      among men who had completed treatment (N = 50). Patients were administered a
      survey that assessed patient knowledge and patients' perceived importance of the
      GSS, as well as demographics, medical factors (e.g., Gleason score at diagnosis),
      and health literacy. Bivariate analyses were conducted to identify associations
      with patient knowledge and perceived importance of the GSS. The sample was
      generally well-educated (48% with a bachelor's degree or higher) and health
      literate (M = 12.9, SD = 2.2, range = 3-15). Despite this, patient knowledge of
      the GSS was low (M = 1.8, SD = 1.4, range = 1-4). Patients' understanding of the
      importance of the GSS was moderate (M = 2.8, SD = 1.0, range = 0-4) and was
      positively associated with GSS knowledge (p < .01). Additionally, GSS knowledge
      was negatively associated with years since biopsy (p < .05). Age and health
      literacy were positively associated with patients' perceived importance of the
      GSS (p < .05), but not with GSS knowledge. Patient knowledge is thus less than
      optimal and would benefit from enhanced communication to maximize shared
      treatment decision-making. Future studies are needed to explore the potential
      utility of a simplified Gleason grading system and improved patient-provider
      communication.

PMID- 29333578
TI  - Insulin resistance and bone: a biological partnership.
AB  - Despite a clear association between type 2 diabetes (T2D) and fracture risk, the
      pathogenesis of bone fragility in T2D has not been clearly elucidated. Insulin
      resistance is the primary defect in T2D. Insulin signalling regulates both bone
      formation and bone resorption, but whether insulin resistance can affect bone has
      not been established. On the other hand, evidence exists that bone might play a
      role in the regulation of glucose metabolism. This article reviews the available
      experimental and clinical evidence on the interplay between bone and insulin
      resistance. Interestingly, a bilateral relationship between bone and insulin
      resistance seems to exist that unites them in a biological partnership.

PMID- 29333580
TI  - Persistent Organochlorine Contaminant Residues in Tissues of Hedgehogs from
      Turkey.
AB  - The residues of persistent organochlorinated pollutants (POPs), namely
      polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) (HCHs,
      CHLs, HCCPs, DDTs, and dicofol congeners) were investigated in the hair and
      muscle of road-killed Erinaceus roumanicus and E. concolor in Turkey. Mean
      residue levels were as follows: in hair, PCBs = 7.43 +/- 4.88 ng/g and OCPs =
      9.21 +/- 1.27 ng/g; in muscle, PCBs = 30.73 +/- 2.51 ng/g and OCPs = 145.04 +/-
      16.59 ng/g. There was no significant difference between species and sex, while
      there was significant difference between habitats and regions in terms of either
      total PCB and OCP levels, or POP levels (p < 0.05). Age was a determinative
      factor for the bio-accumulation of POPs. The contaminant levels were high in the
      species, sample areas, and habitats. The data also showed that tissues of
      hedgehogs are suitable for monitoring and evaluating the bioaccumulation of POP
      levels in Turkey.

PMID- 29333579
TI  - Factors associated with the number and size of renal angiomyolipomas in sporadic
      angiomyolipoma (sAML): a study of adult patients with sAML managed in a Dutch
      tertiary referral center.
AB  - PURPOSE: To describe the patient characteristics, treatments, disease monitoring,
      and kidney function of patients with sporadic angiomyolipoma (sAML), stratified
      by the number and size of renal angiomyolipomas (AMLs). METHODS: Single-center
      retrospective analysis of patients with sAML treated from 1990 to 2015 in a
      dedicated clinic for inheritable tumor syndromes in a tertiary referral center
      from the Netherlands. Patients' first AML assessment at the clinic was defined as
      the index date. Patient characteristics were measured at the index date.
      Treatments, disease monitoring, and kidney function were measured post-index
      date. RESULTS: The study sample included 53 patients followed for a total of
      184.6 patient-years. At the index date, the largest AML was >= 3.5 cm for 26
      patients and < 3.5 cm for 27 patients (including six patients with five or more
      AMLs of < 3.5 cm). As compared to patients with AMLs < 3.5 cm, patients with
      largest AML >= 3.5 cm had higher frequency of pre-index bleeding episodes (31 vs.
      4%), pre-index hypertension (35 vs. 15%), post-index nephrectomy (19 vs. 4%),
      post-index embolization (8 vs. 0%), and post-index renal scans (1.14 vs. 0.74
      scans/year). Kidney impairment was especially pronounced in young adults with AML
      >= 3.5 cm. On average, patients with sAML developed chronic kidney disease stage
      two earlier than the general Dutch population (age 42 vs. 55 years), but later
      than the patients with tuberous sclerosis complex (35 years). CONCLUSIONS:
      Patients with sAML, especially those with larger AMLs, have high disease burden.

PMID- 29333581
TI  - High final energy of gallium arsenide laser increases MyoD gene expression during
      the intermediate phase of muscle regeneration after cryoinjury in rats.
AB  - The aim of this study was to determine the effects of gallium arsenide (GaAs)
      laser on IGF-I, MyoD, MAFbx, and TNF-alpha gene expression during the
      intermediate phase of muscle regeneration after cryoinjury 21 Wistar rats were
      divided into three groups (n = 7 per group): untreated with no injury (control
      group), cryoinjury without GaAs (injured group), and cryoinjury with GaAs (GaAs
      injured group). The cryoinjury was induced in the central region of the tibialis
      anterior muscle (TA). The region injured was irradiated once a day during 14 days
      using GaAs laser (904 nm; spot size 0.035 cm2, output power 50 mW; energy density
      69 J cm-2; exposure time 4 s per point; final energy 4.8 J). Twenty-four hours
      after the last application, the right and left TA muscles were collected for
      histological (collagen content) and molecular (gene expression of IGF-I, MyoD,
      MAFbx, and TNF-alpha) analyses, respectively. Data were analyzed using one-way
      ANOVA at P < 0.05. There were no significant (P > 0.05) differences in collagen
      density and IGF-I gene expression in all experimental groups. There were similar
      (P < 0.05) decreases in MAFbx and TNF-alpha gene expression in the injured and
      GaAs-injured groups, compared to control group. The MyoD gene expression
      increased (P = 0.008) in the GaAs-injured group, but not in the injured group (P
      = 0.338), compared to control group. GaAs laser therapy had a positive effect on
      MyoD gene expression, but not IGF-I, MAFbx, and TNF-alpha, during intermediary
      phases (14 days post-injury) of muscle repair.

PMID- 29333582
TI  - Outpatient erbium:YAG (2940 nm) laser treatment for snoring: a prospective study
      on 40 patients.
AB  - Snoring is a sleep phenomenon due to the partial upper airway obstruction during
      sleep which causes vibration of the tissues of the rhino-oro-hypopharynx and less
      frequently the larynx. This study evaluated the use and effectiveness of the
      erbium:YAG 2940-nm laser as an adjunctive in providing treatment for patients
      suffering from chronic snoring-related sleep disorders. A prospective study of 40
      consecutive patients with snoring and sleep disorders was performed, assessing
      data before and after three Er:YAG laser treatment sessions. During laser
      treatment, the pain was almost absent. There were no side effects, except a very
      mild sore throat in 1 out of 40 patients. The patient's evaluation of
      satisfaction of the results obtained after the treatments showed that 85% of
      cases were very satisfied, 5 patients (12.5%) reported being fairly satisfied
      with the treatment and only 1 subject (2.5%) was not satisfied. Mallampati,
      Friedman Tongue Position, and degree of O (oropharynx) at nose oropharynx
      hypopharynx and larynx classification were significantly decreased after the
      laser sessions. The decrease of Epworth Sleepiness Scale and Visual Analogue
      Scale for loudness of snoring, waking up during sleep because of snoring, dry
      mouth on waking, and choking was all statistically significant. The incidence of
      dreaming during the night also raised significantly; 30/40 (75%) of cases
      perceived less tightness in their throat and better breathing after treatment.
      These results were stable at 20 months follow-up (14-24 q) in 72% of cases.
      Nonsurgical and non-invasive Er:YAG laser treatment demonstrated to be a valid
      procedure in reducing the loudness of snoring.

PMID- 29333583
TI  - The Microbial Community of Tardigrades: Environmental Influence and Species
      Specificity of Microbiome Structure and Composition.
AB  - Symbiotic associations of metazoans with bacteria strongly influence animal
      biology since bacteria are ubiquitous and virtually no animal is completely free
      from them. Tardigrades are micrometazoans famous for their ability to undergo
      ametabolic states (cryptobiosis) but very little information is available on
      potential microbial associations. We characterized the microbiomes of six
      limnoterrestrial tardigrade species belonging to several phylogenetic lines in
      tandem with the microbiomes of their respective substrates. The experimental
      design enabled us to determine the effects of both the environment and the host
      genetic background on the tardigrade microbiome; we were able to define the
      microbial community of the same species sampled from different environments, and
      the communities of different species from the same environment. Our 16S rRNA gene
      amplicon approach indicated that the tardigrade microbiome is species-specific
      and well differentiated from the environment. Tardigrade species showed a much
      lower microbial diversity compared to their substrates, with only one significant
      exception. Forty-nine common OTUs (operational taxonomic units) were classified
      into six bacterial phyla, while four common OTUs were unclassified and probably
      represent novel bacterial taxa. Specifically, the tardigrade microbiome appears
      dominated by Proteobacteria and Bacteroidetes. Some OTUs were shared between
      different species from geographically distant samples, suggesting the associated
      bacteria may be widespread. Putative endosymbionts of tardigrades from the order
      Rickettsiales were identified. Our results indicated that like all other animals,
      tardigrades have their own microbiota that is different among species, and its
      assembly is determined by host genotype and environmental influences.

PMID- 29333585
TI  - Indian Journal of Gastroenterology: The promises fulfilled and waiting for
      fulfillment!

PMID- 29333584
TI  - In focus in HCB.

PMID- 29333586
TI  - Pre-operative templating for knee arthroplasty shows low accuracy with standard X
      rays.
AB  - OBJECTIVES: The purpose of this study was to evaluate the accuracy and
      reliability of pre-operative templating in predicting the size of femoral and
      tibial components and the effect of coronal deformity on templating accuracy.
      METHODS: This was a retrospective study of 39 pre-operative templates prepared by
      three different surgeons with different levels of training. The accuracy and
      reliability measures were evaluated by alpha and kappa coefficients of agreement.
      The analysis of the effect of coronal deformity on the accuracy of the template
      was measured by the Spearman's correlation test. RESULTS: Templating was accurate
      for the femoral component in 28.21% of anterposterior (AP) radiographs and 35.90%
      of lateral radiographs. Kappa coefficients were respectively 0.111 (95%
      confidence interval [95%CI]: -0.19 to 0.241) and 0.200 (95%CI: -0.010 to 0.401),
      indicating poor agreement. Templating accuracy for the tibial component were,
      respectively, 37.61% and 47.01% for AP and lateral views. Kappa coefficients were
      0.186 (95%CI: -0.070 to 0.379) for the AP view and 0.315 (95%CI: -0.199 to 0.431)
      for the lateral view, showing poor and slight agreement respectively. Considering
      a margin of error of +/-1 sizes, the agreement level improved for all components,
      particularly for tibia, where agreement levels become very good. The inter
      observer agreement was fair for all components, except for the lateral view of
      the femoral component, whose agreement was good. The Spearman correlation test
      showed no correlation between accuracy of templating and coronal deformity.
      CONCLUSION: Pre-operative templating is an unreliable and inaccurate tool. There
      is no relation between coronal deformity and accuracy of templating.

PMID- 29333587
TI  - Genetic characterization and modification of a bioethanol-producing yeast strain.
AB  - Yeast Saccharomyces cerevisiae strains isolated from different sources generally
      show extensive genetic and phenotypic diversity. Understanding how genomic
      variations influence phenotypes is important for developing strategies with
      improved economic traits. The diploid S. cerevisiae strain NY1308 is used for
      cellulosic bioethanol production. Whole genome sequencing identified an extensive
      amount of single nucleotide variations and small insertions/deletions in the
      genome of NY1308 compared with the S288c genome. Gene annotation of the assembled
      NY1308 genome showed that 43 unique genes are absent in the S288c genome.
      Phylogenetic analysis suggested most of the unique genes were obtained through
      horizontal gene transfer from other species. RNA-Seq revealed that some unique
      genes were not functional in NY1308 due to unidentified intron sequences. During
      bioethanol fermentation, NY1308 tends to flocculate when certain inhibitors
      (derived from the pretreatment of cellulosic feedstock) are present in the
      fermentation medium. qRT-PCR and genetic manipulation confirmed that the novel
      gene, NYn43, contributed to the flocculation ability of NY1308. Deletion of NYn43
      resulted in a faster fermentation rate for NY1308. This work disclosed the
      genetic characterization of a bioethanol-producing S. cerevisiae strain and
      provided a useful paradigm showing how the genetic diversity of the yeast
      population would facilitate the personalized development of desirable traits.

PMID- 29333589
TI  - New species and new record of the genus Cheloniodiplostomum (Trematoda,
      Proterodiplostomidae, Polycotylinae), parasites of freshwater turtles from
      Argentina.
AB  - The aim of the present paper is to describe a new species of the genus
      Cheloniodiplostomum (Digenea, Proterodiplostomidae) in the Hilaire's toadhead
      turtle Phrynops hilarii from Argentina and to expand the geographic and host
      distribution of Cheloniodiplostomum testudinis. Additionally, we present a
      diagnostic key for Cheloniodiplostomum.

PMID- 29333588
TI  - Nitrogen-fixation activity and the abundance and taxonomy of nifH genes in
      agricultural, pristine, and urban prairie stream sediments chronically exposed to
      different levels of nitrogen loading.
AB  - Small streams exert great influences on the retention and attenuation of nitrogen
      (N) within stream networks. Human land use can lead to increased transport of
      dissolved inorganic N compounds and downstream eutrophication. Microbial activity
      in streams is important for maintaining an actively functioning N cycle.
      Chronically high N loading in streams affects the rates of the central processes
      of the N cycle by increasing rates of nitrification and denitrification, with
      biota exhibiting decreased efficiency of N use. The LINXII project measured N
      cycle parameters in small streams using 15NO3- tracer release experiments. We
      concurrently measured N2 fixation rates in six streams of three types
      (agricultural, pristine, and urban prairie streams) as part of this broader study
      of major N-cycle processes. Nitrogen fixation in streams was significantly
      negatively correlated with nitrate levels, dissolved inorganic N levels, and
      denitrification rates. Algal mat and leaf litter samples generally exhibited the
      highest rates of N2 fixation. The abundance of nifH genes, as measured by real
      time PCR, was marginally correlated with N2-fixation rates, but not to other N
      cycle processes or stream characteristics. The nifH sequences observed were
      assigned to cyanobacteria, Deltaproteobacteria, Methylococcus, and Rhizobia.
      Seasonal changes, disturbances, and varying inputs may encourage a diverse,
      flexible, stable N2-fixing guild. Patchiness in the streams should be considered
      when assessing the overall impact of N2 fixation, since algal biomass exhibited
      high rates of N2 fixation.

PMID- 29333590
TI  - Advantages and Disadvantages in Image Processing with Free Software in Radiology.
AB  - Currently, there are sophisticated applications that make it possible to
      visualize medical images and even to manipulate them. These software applications
      are of great interest, both from a teaching and a radiological perspective. In
      addition, some of these applications are known as Free Open Source Software
      because they are free and the source code is freely available, and therefore it
      can be easily obtained even on personal computers. Two examples of free open
      source software are Osirix Lite(r) and 3D Slicer(r). However, this last group of
      free applications have limitations in its use. For the radiological field,
      manipulating and post-processing images is increasingly important. Consequently,
      sophisticated computing tools that combine software and hardware to process
      medical images are needed. In radiology, graphic workstations allow their users
      to process, review, analyse, communicate and exchange multidimensional digital
      images acquired with different image-capturing radiological devices. These
      radiological devices are basically CT (Computerised Tomography), MRI (Magnetic
      Resonance Imaging), PET (Positron Emission Tomography), etc. Nevertheless, the
      programs included in these workstations have a high cost which always depends on
      the software provider and is always subject to its norms and requirements. With
      this study, we aim to present the advantages and disadvantages of these
      radiological image visualization systems in the advanced management of
      radiological studies. We will compare the features of the VITREA2(r) and AW
      VolumeShare 5(r) radiology workstation with free open source software
      applications like OsiriX(r) and 3D Slicer(r), with examples from specific
      studies.

PMID- 29333592
TI  - 3D Models of Female Pelvis Structures Reconstructed and Represented in
      Combination with Anatomical and Radiological Sections.
AB  - We present a computer program designed to visualize and interact with three
      dimensional models of the main anatomical structures of the female pelvis. They
      are reconstructed from serial sections of corpse, from the Visible Human project
      of the Medical Library of the United States and from serial sections of high
      resolution magnetic resonance. It is possible to represent these three
      dimensional structures in any spatial orientation, together with sectional images
      of corpse and magnetic resonance imaging, in the three planes of space (axial,
      coronal and sagittal) that facilitates the anatomical understanding and the
      identification of the set of visceral structures of this body region. Actually,
      there are few studies that analysze in detail the radiological anatomy of the
      female pelvis using three-dimensional models together with sectional images,
      making use of open applications for the representation of virtual scenes on low
      cost Windows(r) platforms. Our technological development allows the observation
      of the main female pelvis viscera in three dimensions with a very intuitive
      graphic interface. This computer application represents an important training
      tool for both medical students and specialists in gynecology and as a preliminary
      step in the planning of pelvic floor surgery.

PMID- 29333593
TI  - Control of anterior segment using an antero-posterior lingual sliding retraction
      system: a preliminary cone-beam CT study.
AB  - BACKGROUND: This study was performed to evaluate the treatment effects of the
      antero-posterior lingual retractor (APLR), focusing on the 3-dimensional (3D)
      tooth movement of the maxillary anterior teeth and their alveolar bone levels.
      METHODS: En masse retraction was performed using either the C-lingual retractor
      (CLR, C-group, n = 9) or the antero-posterior lingual retractor (APLR, AP-group,
      n = 8). We evaluated 3D movement of the maxillary anterior teeth and alveolar
      bone levels, root length of the central incisors, long axes of the maxillary
      canines, and occlusal plane changes from CBCT images. RESULTS: After retraction,
      the central incisors were more significantly intruded and their root apex was
      more retracted in the AP-group. The long axis of the canine was well maintained
      in the AP-group. There were no differences in the steepness of occlusal plane and
      the incidence of alveolar bone loss or of root resorption during en masse
      retraction with the two retractors. CONCLUSIONS: The clockwise bowing effect of
      the anterior segment was less with the APLR, which prevented unwanted canine
      movement.

PMID- 29333591
TI  - Differential Inhibition of Nav1.7 and Neuropathic Pain by Hybridoma-Produced and
      Recombinant Monoclonal Antibodies that Target Nav1.7 : Differential activities of
      Nav1.7-targeting monoclonal antibodies.
AB  - The voltage-gated Na+ channel subtype Nav1.7 is important for pain and itch in
      rodents and humans. We previously showed that a Nav1.7-targeting monoclonal
      antibody (SVmab) reduces Na+ currents and pain and itch responses in mice. Here,
      we investigated whether recombinant SVmab (rSVmab) binds to and blocks Nav1.7
      similar to SVmab. ELISA tests revealed that SVmab was capable of binding to
      Nav1.7-expressing HEK293 cells, mouse DRG neurons, human nerve tissue, and the
      voltage-sensor domain II of Nav1.7. In contrast, rSVmab showed no or weak binding
      to Nav1.7 in these tests. Patch-clamp recordings showed that SVmab, but not
      rSVmab, markedly inhibited Na+ currents in Nav1.7-expressing HEK293 cells.
      Notably, electrical field stimulation increased the blocking activity of SVmab
      and rSVmab in Nav1.7-expressing HEK293 cells. SVmab was more effective than
      rSVmab in inhibiting paclitaxel-induced mechanical allodynia. SVmab also bound to
      human DRG neurons and inhibited their Na+ currents. Finally, potential reasons
      for the differential efficacy of SVmab and rSVmab and future directions are
      discussed.

PMID- 29333594
TI  - RAS testing for colorectal cancer patients is reliable in European laboratories
      that pass external quality assessment.
AB  - Wild-type status of KRAS and the NRAS gene (exon 2, 3, and 4) in the tumor should
      be determined before treatment of metastatic colorectal cancer (mCRC) patients
      with EGFR-targeting agents. There is a large variation in test methods to
      determine RAS status, and more sensitive detection methods were recently
      introduced. Data from quality assessment programs indicate substantial error
      rates. This study assessed the completeness and correctness of RAS testing in
      European laboratories that successfully passed external quality assessment (EQA).
      Participants were requested to send material of their most recent ten patients
      with mCRC who had been tested for RAS status. Isolated DNA, a hematoxylin and
      eosin stained tissue slide with a marked area for macrodissection and
      accompanying patient reports were requested. Samples were reevaluated in a
      reference laboratory by using a next-generation sequencing approach. In total, 31
      laboratories sent in the requested material (n = 309). Despite regulations for
      anti-EGFR therapy, one institute did not perform full RAS testing. Reanalysis was
      possible for 274 samples with sufficient DNA available. In the hotspot codons of
      KRAS and NRAS, seven discordant results were obtained in total, five of them
      leading to a different prediction of anti-EGFR therapy efficacy (2%; n = 274).
      Results show that oncologists can rely on the quality of laboratories with good
      performance in EQA. Oncologists need to be aware that the testing laboratory
      participates successfully in EQA programs. Some EQA providers list the good
      performing laboratories on their website.

PMID- 29333595
TI  - Implanted Closed-Loop Gastric Electrical Stimulation (CLGES) System with Sensor
      Based Feedback Safely Limits Weight Regain at 24 Months.
AB  - BACKGROUND: Weight regain following bariatric surgery is not uncommon. Safe,
      effective weight loss treatment up to 1 year has been reported with the closed
      loop gastric electrical stimulation (CLGES) system. Continuous recording of
      eating and activity behavior by onboard sensors is one of the novel features of
      this closed-loop electrical stimulation therapy, and may provide improved long
      term weight maintenance by enhancing aftercare. METHODS: Four centers
      participating in a 12-month prospective multicenter randomized study monitored
      all implanted participants (n = 47) up to 24 months after laparoscopic
      implantation of a CLGES system. Weight loss, safety, quality of life (QOL), and
      cardiac risk factors were analyzed. RESULTS: Weight regain was limited in the 35
      (74%) participants remaining enrolled at 24 months. Mean percent total body
      weight loss (%TBWL) changed by only 1.5% between 12 and 24 months, reported at
      14.8% (95% CI 12.3 to 17.3) and 13.3% (95% CI 10.7 to 15.8), respectively. The
      only serious device-/procedure-related adverse events were two elective system
      replacements due to lead failure in the first 12 months, while improvements in
      QOL and cardiovascular risk factors were stable thru 24 months. CONCLUSION:
      During the 24 month follow-up, CLGES was shown to limit weight regain with strong
      safety outcomes, including no serious adverse events in the second year. We
      hypothesize that CLGES and objective sensor-based behavior data combined to
      produce behavior change. The study supports CLGES as a safe obesity treatment
      with potential for long-term health benefits. TRIAL REGISTRATION:
      ClinicalTrials.gov identifier: NCT01448785.

PMID- 29333596
TI  - Risk of adverse events associated with front-line anti-myeloma treatment in
      Medicare patients with multiple myeloma.
AB  - This study aims to examine the risks of adverse events associated with anti
      multiple myeloma (MM) therapies in a large population-based cohort of elderly
      patients with MM. Patients diagnosed with advanced MM from 2005 through 2009 and
      receiving anti-MM therapy were identified from the Surveillance, Epidemiology,
      and End Results (SEER)-Medicare-linked data. We compared safety outcomes between
      novel agents (proteasome inhibitor (PI) and immunomodulatory drugs (IMiD)) and
      other therapies and between PI- or IMiD-based regimens and PI plus IMiD
      combination regimens. Of 2587 patients with advanced MM, 2048 (79%) received
      novel agents and 539 (21%) received other therapies. Patients with preexisting
      anemia and thrombocytopenia were significantly more likely to receive novel
      agents (85.9 vs. 82.4%, P = 0.038; 13.8 vs. 10.4%, P = 0.036), while those with
      preexisting cardiovascular disease and hypertension were significantly less
      likely to receive novel agents (73.4 vs. 79.8%, P = 0.003; 81.3 vs. 85.2%, P =
      0.035). The hazard ratios for anemia, peripheral neuropathy, and thromboembolic
      events for patients receiving novel agents compared with those receiving other
      therapies were 1.19 (95% CI, 1.06-1.32), 1.57 (95% CI, 1.15-2.15), and 1.31 (95%
      CI, 1.03-1.67). The hazard ratios for anemia, neutropenia, and thromboembolic
      events for patients receiving PI plus IMiD combination therapies compared with
      those receiving PI- or IMiD-based therapies were 1.31 (95% CI, 1.12-1.54), 1.66
      (95% CI, 1.27-2.18, and 1.37 (95% CI, 1.02-1.86). Novel agents significantly
      increased the risk of anemia, peripheral neuropathy, and thromboembolic events.
      PI plus IMiD combination therapies were associated with significantly higher risk
      for anemia, neutropenia, and thromboembolic events.

PMID- 29333597
TI  - TP53 polymorphism in plasma cell myeloma.
AB  - INTRODUCTION: Significant and accessible predictive factors for bortezomib
      treatment in plasma cell myeloma (PCM) are still lacking. TP53 codon 72
      polymorphism (P72R) results in proline (P) or arginine (R) at 72 amino acid
      position, which causes synthesis of proteins with distinct functions. The aims of
      our study were to: 1) analyze whether this polymorphism is associated with an
      increased risk of PCM; 2) study whether the P72R polymorphism affects overall
      survival (OS) among PCM patients; 3) assess the possible association of the P72R
      polymorphism with sensitivity to bortezomib in cell cultures derived from PCM
      patients. MATERIAL AND METHODS: Genomic DNA from newly diagnosed 59 patients
      (without IgVH gene rearrangements and TP53 deletions) and 50 healthy blood donors
      were analyzed by RFLP-PCR to identify TP53 polymorphism. Chromosomal aberrations
      were detected by use of cIg-FISH. The lymphocyte cell cultures from a subgroup of
      40 PCM patients were treated with bortezomib (1, 2 and 4 nM). RESULTS: The P
      allele of the P72R polymorphism was more common than the R allele in PMC patients
      compared to controls (39% vs. 24%), and the difference was significant (p =
      0.02). The PP and PR genotypes (in combina-tion) were more frequent among cases
      than in controls (65% vs. 42%, OR = 2.32, p = 0.04). At the cell culture level
      and 2 nM bortezomib concentration the PP genotype was associated with higher
      necrosis rates (10.5%) compared to the PR genotype (5.7%, p = 0.006) or the RR
      genotype (6.3%, p = 0.02); however, no effect of genotypes was observed at
      bortezomib concentrations of 1 and 4 nM. The shortest OS (12 months) was observed
      in patients with the PP genotype compared to patients with the PR or RR genotypes
      (20 months) (p = 0.04). CONCLUSIONS: The results suggest that P72R polymorphisms
      may be associated with an increased PCM risk and may affect OS of PCM patients.
      However, we saw no consistent results of the polymorphism effect on apoptosis and
      necrosis in cell cultures derived from PCM patients. Further studies are need in
      this regard.

PMID- 29333598
TI  - Rainer Walter Guillery FRS, 28th August 1929-7th April 2017.

PMID- 29333599
TI  - Developmental coordination disorder: the role of executive functions.

PMID- 29333600
TI  - The model of children's social adjustment under the gender-roles absence in
      single-parent families.
AB  - This study aimed to evaluate the effects of the gender-role types and child
      rearing gender-role attitude of the single-parents, as well as their children's
      gender role traits and family socio-economic status, on social adjustment. We
      recruited 458 pairs of single parents and their children aged 8-18 by purposive
      sampling. The research tools included the Family Socio-economic Status
      Questionnaire, Sex Role Scales, Parental Child-rearing Gender-role Attitude Scale
      and Social Adjustment Scale. The results indicated: (a) single mothers' and their
      daughters' feminine traits were both higher than their masculine traits, and
      sons' masculine traits were higher than their feminine traits; the majority
      gender-role type of single parents and their children was androgyny; significant
      differences were found between children's gender-role types depending on
      different raiser, the proportion of girls' masculine traits raised by single
      fathers was significantly higher than those who were raised by single mothers;
      (b) family socio-economic status and single parents' gender-role types positively
      influenced parental child-rearing gender-role attitude, which in turn, influenced
      the children's gender traits, and further affected children's social adjustment.

PMID- 29333602
TI  - Children's Perceptions of Economic Groups in a Context of Limited Access to
      Opportunities.
AB  - Children (N = 267, ages 8-14 years, M = 11.61 years, middle to upper-middle
      income) made predictions regarding groups of same-aged peers from high-wealth and
      low-wealth backgrounds. The context involved granting access to a special
      opportunity. From middle childhood to early adolescence children increasingly
      expected both high- and low-wealth groups to want access to opportunities for
      their own group. However, children viewed high-wealth groups as motivated in part
      by selfishness and low-wealth groups as concerned in part with broader economic
      inequality. Finally, the higher children's family income, the more they expected
      group-serving tendencies. These findings revealed children's perceptions of
      exclusive preferences between economic groups, negative stereotypes about high
      wealth children, and awareness of some of the constraints faced by low-wealth
      children.

PMID- 29333601
TI  - Risk factors for stress urinary incontinence after native-tissue vaginal repair
      of pelvic organ prolapse.
AB  - OBJECTIVE: To identify risk factors for postoperative stress urinary incontinence
      (POSUI) after native-tissue prolapse repair without a concomitant anti
      incontinence procedure. METHODS: The present single-center retrospective study
      included women with genital prolapse who underwent high uterosacral ligament
      suspension without a concomitant anti-incontinence procedure during 2008-2013.
      Univariate and multivariate analyses were performed to identify risk factors for
      POSUI (identified through clinical interview and International Consultation on
      Incontinence Modular Questionnaire-Short Form [ICIQ-SF] self-administration) at 6
      months. RESULTS: In total, 87 (20.9%) of 417 women developed POSUI. Preoperative
      stress urinary incontinence (SUI) and urodynamically diagnosed SUI were
      significantly associated with POSUI; moreover, women with POSUI had a higher
      preoperative ICIQ-SF score, a lower opening detrusor pressure, and a lower
      detrusor pressure at maximum flow than did women without POSUI (P<0.05 for all
      comparisons). In the multivariate analysis, preoperative SUI (odds ratio 3.11), a
      detrusor pressure at maximum flow of less than 30 cm H2 O (odds ratio 2.93), and
      urodynamically diagnosed SUI (odds ratio 2.26) were independent risk factors for
      POSUI. CONCLUSION: Preoperative urodynamic parameters, obtained before prolapse
      repair surgery, were associated with POSUI and could be useful in providing
      adequate counseling to facilitate decision making on whether to add a concomitant
      anti-incontinence procedure.

PMID- 29333603
TI  - Could conjunctivitis in patients with atopic dermatitis treated with dupilumab be
      caused by colonization with Demodex and increased interleukin-17 levels?

PMID- 29333605
TI  - Report on oral health status and treatment needs of 5-15 years old children with
      sensory deficits in Chennai, India.

PMID- 29333604
TI  - Adiponectin inhibits inflammatory cytokines production by Beclin-1
      phosphorylation and B-cell lymphoma 2 mRNA destabilization: role for autophagy
      induction.
AB  - BACKGROUND AND PURPOSE: Adiponectin potently suppresses inflammatory mediator
      production. Autophagy is known to play a critical role in the modulation of
      inflammatory responses by adiponectin. However, the underlying mechanisms are not
      clearly understood. Interaction between Beclin-1 and B-cell lymphoma 2 (Bcl-2) is
      a critical event in autophagy induction. We examined the effects of globular
      adiponectin (gAcrp) on the Beclin-1/Bcl-2 association and its underlying
      mechanisms. EXPERIMENTAL APPROACH: The effect of gAcrp on the interaction between
      Beclin-1 and Bcl-2 was examined by immunoprecipitation followed by Western
      blotting. To elucidate the underlying mechanisms, we determined the effects of
      gAcrp on Beclin-1 phosphorylation and Bcl-2 mRNA stability, and investigated
      their role in the suppression of inflammatory mediators using pharmacological
      inhibitors and transient target gene knockdown. KEY RESULTS: Globular adiponectin
      disrupted the association between Beclin-1 and Bcl-2 and increased Beclin-1
      phosphorylation at Thr119 , critical residue for binding with Bcl-2, via a death
      associated protein kinase-1 (DAPK1)-dependent mechanism. Moreover, gAcrp reduced
      Bcl-2 expression via Bcl-2 mRNA destabilization, without significantly affecting
      Bcl-2 promoter activity and protein degradation, which was mediated by
      tristetraprolin (TTP) induction. Finally, DAPK1 and TTP were shown to play key
      roles in gAcrp-induced autophagosome formation and suppression of LPS-stimulated
      TNF-alpha and IL-1beta expression. CONCLUSION AND IMPLICATIONS: Beclin-1
      phosphorylation and Bcl-2 mRNA destabilization mediated by DAPK1 and TTP are
      crucial events leading to autophagy and the suppression of inflammatory cytokine
      production by gAcrp. These results provide novel mechanisms underlying
      adiponectin's modulation of inflammatory responses. DAPK and TTP are potential
      therapeutic targets for the management of inflammation.

PMID- 29333606
TI  - Genetic relationships among Vietnamese local pigs investigated using genome-wide
      SNP markers.
AB  - Vietnam is one of the most important countries for pig domestication, and a total
      of 26 local breeds have been reported. In the present study, genetic
      relationships among the various pig breeds were investigated using 90 samples
      collected from local pigs (15 breeds) in 15 distantly separated, distinct areas
      of the country and six samples from Landrace pigs in Hanoi as an out-group of a
      common Western breed. All samples were genotyped using the Illumina Porcine SNP60
      v2 Genotyping BeadChip. We used 15 160-15 217 SNPs that showed a high degree of
      polymorphism in the Vietnamese breeds for identifying genetic relationships among
      the Vietnamese breeds. Principal components analysis showed that most pigs
      indigenous to Vietnam formed clusters correlated with their original geographic
      locations. Some Vietnamese breeds formed a cluster that was genetically related
      to the Western breed Landrace, suggesting the possibility of crossbreeding. These
      findings will be useful for the conservation and management of Vietnamese local
      pig breeds.

PMID- 29333607
TI  - Arabidopsis MLO2 is a negative regulator of sensitivity to extracellular reactive
      oxygen species.
AB  - The atmospheric pollutant ozone (O3 ) is a strong oxidant that causes
      extracellular reactive oxygen species (ROS) formation, has significant ecological
      relevance, and is used here as a non-invasive ROS inducer to study plant
      signalling. Previous genetic screens identified several mutants exhibiting
      enhanced O3 sensitivity, but few with enhanced tolerance. We found that loss-of
      function mutants in Arabidopsis MLO2, a gene implicated in susceptibility to
      powdery mildew disease, exhibit enhanced dose-dependent tolerance to O3 and
      extracellular ROS, but a normal response to intracellular ROS. This phenotype is
      increased in a mlo2 mlo6 mlo12 triple mutant, reminiscent of the genetic
      redundancy of MLO genes in powdery mildew resistance. Stomatal assays revealed
      that enhanced O3 tolerance in mlo2 mutants is not caused by altered stomatal
      conductance. We explored modulation of the mlo2-associated O3 tolerance, powdery
      mildew resistance, and early senescence phenotypes by genetic epistasis analysis,
      involving mutants with known effects on ROS sensitivity or antifungal defence.
      Mining of publicly accessible microarray data suggests that these MLO proteins
      regulate accumulation of abiotic stress response transcripts, and transcript
      accumulation of MLO2 itself is O3 responsive. In summary, our data reveal MLO2 as
      a novel negative regulator in plant ROS responses, which links biotic and abiotic
      stress response pathways.

PMID- 29333608
TI  - The synergistic effect of PDT and oxacillin on clinical isolates of
      Staphylococcus aureus.
AB  - BACKGROUND: Staphylococcus aureus is a major pathogen in clinical microbiology.
      It is known to cause infections at various body sites and can be life
      threatening. The development of resistance to many well-established antibiotic
      treatments and the prevalence of methicillin-resistant S. aureus (MRAS) among
      hospital patients and the general community pose challenges in treating the
      pathogen. The antimicrobial effect of photodynamic therapy (PDT) has been a
      subject of study for a long time and can offer new strategies for dealing with
      resistant strains. OBJECTIVE: In our study, we searched for a positive
      synergistic relationship between PDT and the standard antibiotics used to treat
      S. aureus and MRSA infections. MATERIALS AND METHODS: The phototoxic profile of
      deuteroporphyrin (DP) in both resistant and susceptible clinical strains of S.
      aureus was determined by plating of treated and untreated broth cultures.
      Electron microscopy imaging was done to explore possible sites of damage and free
      radical accumulation in the cells during DP-PDT. Minimal inhibitory concentration
      (MIC) of oxacillin, gentamicin, vancomycin, rifampin, and fusidic acid was
      determined using the broth dilution method, and the checkerboard method was used
      to detect and evaluate the synergistic potential of DP-PDT and antibiotic
      combinations. A synergistic combination was further characterized using broth
      cultures and plating. RESULTS: DP-PDT using a light dose of 15 J/cm2 showed a
      bactericidal effect even with a small concentration of 17 MUM DP. Transmission
      electron microscopy indicated profound damage in the cell wall and cell membrane,
      and the appearance of mesosome-like structures. Free radicals tend to localize in
      the cell membrane and inside the mesosome. No synergistic effect was detected by
      combining PDT with gentamicin, vancomycin, rifampin, and fusidic acid treatments.
      A positive synergistic effect was observed only in DP-PDT-oxacillin combined
      treatment using the checkerboard method. The effect was observed in clinical
      antibiotic-resistant isolates after DP-PDT using a light dose of 46 J/cm2 and
      small concentrations of DP. Oxacillin MIC decreased below 2 MUg/ml in resistant
      strains under such conditions. Cultures which did not undergo new cycles of DP
      PDT recovered their original oxacillin resistance after a few generations.
      CONCLUSIONS: PDT with porphyrins shows possible new therapeutic options in
      treating drug-resistant S. aureus at body sites suitable for irradiation. The
      synergistic effect of DP-PDT with oxacillin on clinical strains illustrates the
      potential of PDT to augment traditional antibiotic treatment based on cell wall
      inhibitors. Lasers Surg. Med. 50:535-551, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 29333609
TI  - Runs of homozygosity reveal genome-wide autozygosity in Italian sheep breeds.
AB  - The availability of dense single nucleotide polymorphism (SNP) assays allows for
      the determination of autozygous segments based on runs of consecutive homozygous
      genotypes (ROH). The aim of the present study was to investigate the occurrence
      and distribution of ROH in 21 Italian sheep breeds using medium-density SNP
      genotypes in order to characterize autozygosity and identify genomic regions that
      frequently appeared in ROH within individuals, namely ROH islands. After
      filtering, the final number of animals and SNPs retained for analyses were 502
      and 46 277 respectively. A total of 12 302 ROH were identified. The mean number
      of ROH per breed ranged from 10.58 (Comisana) to 44.54 (Valle del Belice). The
      average length of ROH across breeds was 4.55 Mb and ranged from 3.85 Mb
      (Biellese) to 5.51 Mb (Leccese). Valle del Belice showed the highest value of
      inbreeding on the basis of ROH (FROH  = 0.099), whereas Comisana showed the
      lowest (FROH  = 0.016), and high standard deviation values revealed high
      variability in autozygosity levels within each breed. Differences also existed in
      the length of ROH. Analysis of the distribution of ROH according to their size
      showed that, for all breeds, the majority of the detected ROH were <10 Mb in
      length, with a few long ROH >25 Mb. The levels of ROH that we estimated here
      reflect the inbreeding history of the investigated sheep breeds. These results
      also highlight that ancient and recent inbreeding have had an impact on the
      genome of the Italian sheep breeds and suggest that several animals have
      experienced recent autozygosity events. Comisana and Bergamasca appeared as the
      less consanguineous breeds, whereas Barbaresca, Leccese and Valle del Belice
      showed ROH patterns typically produced by recent inbreeding. Moreover, within the
      genomic regions most commonly associated with ROH, several candidate genes were
      detected.

PMID- 29333610
TI  - Clinical features and treatment of nonalcoholic fatty liver disease across the
      Asia Pacific region-the GO ASIA initiative.
AB  - BACKGROUND: The Gut and Obesity Asia (GO ASIA) workgroup was formed to study the
      relationships between obesity and gastrointestinal diseases in the Asia Pacific
      region. AIM: To study factors associated with nonalcoholic steatohepatitis (NASH)
      and advanced fibrosis, and medical treatment of biopsy-proven nonalcoholic fatty
      liver disease (NAFLD) patients. METHODS: Retrospective study of biopsy-proven
      NAFLD patients from centres in the GO ASIA Workgroup. Independent factors
      associated with NASH and with advanced fibrosis on binary logistic regression
      analyses in a training cohort were used for the development of their
      corresponding risk score, which were validated in a validation cohort. RESULTS:
      We included 1008 patients from nine centres across eight countries (NASH 62.9%,
      advanced fibrosis 17.2%). Independent predictors of NASH were body mass index
      >=30 kg/m2 , diabetes mellitus, dyslipidaemia, alanine aminotransferase >=88 U/L
      and aspartate aminotransferase >=38 U/L, constituting the Asia Pacific NASH risk
      score. A high score has a positive predictive value of 80%-83% for NASH.
      Independent predictors of advanced fibrosis were age >=55 years, diabetes
      mellitus and platelet count <150 * 109 /L, constituting the Asia-Pacific NAFLD
      advanced fibrosis risk score. A low score has a negative predictive value of 95%
      96% for advanced fibrosis. Only 1.7% of patients were referred for structured
      lifestyle program, 4.2% were on vitamin E, and 2.4% were on pioglitazone.
      CONCLUSIONS: More severe liver disease can be suspected or ruled out based on
      factors identified in this study. Utilisation of structured lifestyle program,
      vitamin E and pioglitazone was limited despite this being a cohort of biopsy
      proven NAFLD patients with majority of patients having NASH.

PMID- 29333611
TI  - Cognitive dysfunction after generalized tonic-clonic status epilepticus in
      adults.
AB  - OBJECTIVES: Generalized tonic-clonic status epilepticus (GTC-SE) is considered a
      risk for cognitive impairment. Research with standardized tools is scarce and non
      conclusive. We systematically assessed short-term and long-term cognitive
      function after GTC-SE. MATERIALS AND METHODS: Thirty-three patients were tested
      after the clinical post-ictal phase of GTC-SE (timepoint 1) and again after 1
      year (timepoint 2). Twenty controls were examined with the same tests. Tests from
      Cambridge Neuropsychological Test Automated Battery were used. Motor screening
      test (MOT) assessed motor speed, delayed matching to sample (DMS) and paired
      associates learning (PAL) assessed memory, and Stockings of Cambridge (SOC)
      assessed executive function. Estimated premorbid IQ and radiologically visible
      brain lesions were controlled for in adjusted results. Outcome measures were z
      scores, the number of standard deviations a score deviates from the mean of a
      norm population. RESULTS: At timepoint 1, unadjusted patient results were
      significantly below both norm and control group performances on all subtests.
      Patient mean was 1.9 z-scores below controls (P < .001) on PAL total errors.
      Results remained significant for PAL and DMS after adjustments. Patient results
      improved at timepoint 2, but memory tests remained lower than norms and for
      controls. An executive dysfunction emerged on the most complex SOC stage (z-score
      difference -0.83; P = .008, adjusted difference -0.94; P = .02). CONCLUSIONS:
      Memory and learning impairment in the early phase after SE and late developing
      executive dysfunction remained significant after adjusting for estimated
      premorbid IQ and pre-SE brain lesions. Results suggest that GTC-SE poses a risk
      for cognitive impairment.

PMID- 29333612
TI  - Fosfomycin residues in colostrum: Impact on morpho-physiology and microbiology of
      suckling piglets.
AB  - Fosfomycin is a broad-spectrum bactericidal antibiotic widely used in pig farms
      for the treatment of a wide variety of bacterial infections. In this study, the
      elimination of disodium fosfomycin in colostrum/milk of the sow and the impact of
      this antibiotic on the microbiota and intestinal morpho-physiology of suckling
      piglets were analyzed. The average amount of fosfomycin eliminated in colostrum
      (after administration of 15 mg/kg IM) during the first 10 hr postpartum was 0.85
      MUg/ml, and the mean residual amount ingested by the piglets was 0.26 mg/kg. The
      elimination profile of fosfomycin concentrations in colostrum occurs at a time of
      profound changes in the morpho-physiology of the gastrointestinal tract of the
      piglet. However, the studied concentrations did not produce imbalances on the
      microbiota or on the morpho-physiology of the gastrointestinal tract of the
      piglet. Concentrations of fosfomycin were maintained in the mammary gland above
      the MIC for more than 8 hr for pathogenic bacteria of productive importance. This
      would indicate that fosfomycin may be considered safe for the specific treatment
      of bacterial infectious processes in sows during the peri- and postpartum period.
      This first study with disodium fosfomycin stimulates awareness in the proper use
      of antimicrobials at farrowing.

PMID- 29333613
TI  - Pharmacokinetics, pharmacodynamics and clinical use of trazodone and its active
      metabolite m-chlorophenylpiperazine in the horse.
AB  - Trazodone is a serotonin receptor antagonist and reuptake inhibitor used
      extensively as an anxiolytic in human and small animal veterinary medicine. The
      aims of this study were to determine the pharmacokinetics of oral trazodone in
      experimental horses and to evaluate the effect of oral trazodone in clinical
      horses. Six experimental horses were administered trazodone at 7.5 or 10 mg/kg.
      Plasma concentrations of trazodone and its metabolite (m-CPP) were determined via
      UPLC-MS/MS. Noncompartmental pharmacokinetic analysis, sedation and ataxia scores
      were determined. Trazodone was rapidly absorbed after oral administration with a
      maximum concentration of 2.5-4.1 MUg/ml and half-life of the terminal phase of
      approximately 7 hr. The metabolite was present at low levels in all horses,
      representing only 2.5% of the total area under the curve. In experimental horses,
      concentration-dependent sedation and ataxia were noted, lasting up to 12 hr. For
      clinical cases, medical records of horses treated with trazodone for various
      abnormal behaviours were reviewed and data were summarized. Trazodone was
      successful in modifying behavioural problems to some degree in 17 of 18 clinical
      cases. Tolerance and subsequent lack of drug effect occurred in two of 18
      clinical cases following 14 or 21 days of use. In both populations of horses,
      adverse effects attributed to trazodone include oversedation, muscle
      fasciculations and transient arrhythmias.

PMID- 29333614
TI  - The effect of risk factor misclassification on the partial population
      attributable risk.
AB  - The partial population attributable risk (pPAR) is used to quantify the
      population-level impact of preventive interventions in a multifactorial disease
      setting. In this paper, we consider the effect of nondifferential risk factor
      misclassification on the direction and magnitude of bias of pPAR estimands and
      related quantities. We found that the bias in the uncorrected pPAR depends
      nonlinearly and nonmonotonically on the sensitivities, specificities, relative
      risks, and joint prevalence of the exposure of interest and background risk
      factors, as well as the associations between these factors. The bias in the
      uncorrected pPAR is most dependent on the sensitivity of the exposure. The
      magnitude of bias varies over a large range, and in a small region of the
      parameter space determining the pPAR, the direction of bias is away from the
      null. In contrast, the crude PAR can only be unbiased or biased towards the null
      by risk factor misclassification. The semiadjusted PAR is calculated using the
      formula for the crude PAR but plugs in the multivariate-adjusted relative risk.
      Because the crude and semiadjusted PARs continue to be used in public health
      research, we also investigated the magnitude and direction of the bias that may
      arise when using these formulae instead of the pPAR. These PAR estimators and
      their uncorrected counterparts were calculated in a study of risk factors for
      colorectal cancer in the Health Professionals Follow-up Study, where it was found
      that because of misclassification, the pPAR for low folate intake was
      overestimated with a relative bias of 48%, when red meat and alcohol intake were
      treated as misclassified risk factors that are not modified, and when red meat
      was treated as the modifiable risk factor, the estimated value of the pPAR went
      from 14% to 60%, further illustrating the extent to which misclassification can
      bias estimates of the pPAR.

PMID- 29333615
TI  - Circular RNA hsa_circ_0000567 can be used as a promising diagnostic biomarker for
      human colorectal cancer.
AB  - BACKGROUND: Recent studies have revealed that circular RNAs are involved in the
      biological process of some kinds of human cancers. However, little is known about
      their diagnostic values and functions in colorectal cancer (CRC). METHODS: The
      expression levels of hsa_circ_0000567 in 102 paired CRC tissues and adjacent
      noncancerous tissues, 5 CRC cell lines, and a normal colorectal epithelial cell
      line were detected by quantitative real-time polymerase chain reaction (qRT-PCR).
      The correlations between hsa_circ_0000567 expression levels and the
      clinicopathological factors of patients with CRC were analyzed. Furthermore, the
      loss-of-function assay was performed to investigate the functions of
      hsa_circ_0000567 in vitro. Finally, a receiver operating characteristic (ROC)
      curve was established to evaluate the diagnostic value of hsa_circ_0000567.
      RESULTS: Hsa_circ_0000567 expression was significantly downregulated in CRC
      tissues and CRC cell lines. In addition, the decreased hsa_circ_0000567
      expression in CRC was negatively correlated with tumor size (P = .011), lymph
      metastasis (P = .003), distal metastasis (P < .0001), and tumor-node-metastasis
      (TNM) stage (P = .003) in CRC. Moreover, knockdown of hsa_circ_0000567 promoted
      CRC cells proliferation and migration in vitro. Importantly, the area under the
      ROC curve (AUC) was 0.8653, which indicates hsa_circ_0000567 can serve as a
      diagnostic biomarker. CONCLUSION: Hsa_circ_0000567 may be a novel suppressor and
      a potential diagnosis biomarker in CRC.

PMID- 29333616
TI  - Determination of vitamins K1 , MK-4, and MK-7 in human serum of postmenopausal
      women by HPLC with fluorescence detection.
AB  - BACKGROUND: New high-performance liquid chromatography (HPLC) method was
      developed for the determination of vitamin K1 and two forms of vitamin K2 (MK-4
      and MK-7) in human serum, and the levels of vitamin K were determined in 350
      samples of postmenopausal women. METHODS: Vitamin K was determined by HPLC with
      fluorescence detection after postcolumn zinc reduction. The detection was
      performed at 246 nm (excitation) and 430 nm (emission). The internal standard and
      2 mL of ethanol were added to 500 MUL of serum. The mixture was extracted with 4
      mL of hexane, and solid phase extraction was then used. RESULTS: The HLPC method
      was fully validated. The intra- and interday accuracy and precision were
      evaluated on two QC samples by multiple analysis, and CV were less than 10%. The
      limit of quantification for MK-4 was found at 0.04 ng/mL, for K1 0.03 ng/mL, and
      for MK-7 0.03 ng/mL. The mean recoveries of the corresponding compounds were 98%
      110%. Serum levels of MK-4, K1 , and MK-7 in postmenopausal women with
      osteoporosis were 0.890 +/- 0.291 ng/mL, 0.433 +/- 0.394 ng/mL, and 1.002 +/-
      1.020 ng/mL, respectively (mean +/- SD). Serum levels of MK-4, K1 , and MK-7 in
      postmenopausal women without osteoporosis were 0.825 +/- 0.266 ng/mL, 0.493 +/-
      0.399 ng/mL, and 1.186 +/- 1.076 ng/mL, respectively (mean +/- SD). CONCLUSION:
      New HPLC method for the determination of vitamins K1 , MK-4, and MK-7 in serum
      was evaluated and validated. This method is highly specific and sensitive with
      the low limit of quantification.

PMID- 29333617
TI  - A perceptive plus in Parkinson's disease.

PMID- 29333618
TI  - Age-associated urethral dysfunction in urethane-anesthetized rats.
AB  - AIMS: We aimed to investigate the age-associated changes in movement coordination
      between the urinary bladder and the urethra in rats. METHODS: A total of 17
      female Sprague-Dawley rats were used. The rats were divided into young (3 months
      old) and middle-aged (12-15 months old) groups. In both groups, isovolumetric
      cystometry and urethral perfusion pressure (UPP) measurements were performed
      under urethane anesthesia. After the rhythmic bladder contractions stabilized, L
      arginine, a nitric oxide (NO) substrate (100 mg/kg), was administered
      intravenously in both groups. Subsequently, N-nitro-L-arginine methyl ester
      hydrochloride (L-NAME) (50 mg/kg) was injected intravenously to inhibit NO
      synthase activity in both groups. RESULTS: UPP change, defined as UPP nadir minus
      baseline UPP, was significantly smaller in middle-aged rats (64%) than in young
      rats (P < 0.05). The mean amplitude of high-frequency oscillations (HFOs) of the
      external urethral sphincter was also significantly lower (62%) in middle-aged
      rats than that in young rats (P < 0.05). Urethral contraction during UPP change
      was also noted in middle-aged rats. This urethral contraction disappeared after L
      arginine administration. UPP nadir during bladder contraction was inhibited by L
      NAME in both groups. UPP change was greater in middle-aged rats than in young
      rats, and 3 out of 9 middle-aged rats showed a detrusor-sphincter dyssynergia
      pattern after L-NAME. CONCLUSIONS: The results indicated that aging induces
      dysfunction in movement coordination between the urinary bladder and the urethra.
      Thus, age-associated urethral dysfunctions may lead to inefficient voiding with
      increased post-void residual urine volume, which is often observed in elderly
      populations.

PMID- 29333620
TI  - In-center hemodialysis education: Challenges and innovations in training of
      fellows in nephrology.
AB  - The in-center dialysis unit and practice of dialysis, in the current multi-team
      approach, requires knowledge and skills in all the domains including medical
      expert, communicator, collaborator, scholar, health advocate, and leader. We are
      tasked as a community, to embrace and incentivize new innovations and technology
      to address these needs for our post graduate trainees. These innovations must
      address the basic principles of dialysis, quality improvement, technical and
      procedural skills as well as leadership and administration skills. The teaching
      methods and innovations must also be challenged to demonstrate the translation
      into adoption and improvements in practice to demonstrate success. This article
      will review the current state of the training curriculum in Nephrology for in
      center hemodialysis and address some of the recent innovations.

PMID- 29333619
TI  - Surrogate scale for evaluating respiratory function based on complete blood count
      parameters.
AB  - BACKGROUND: In this study, we aimed to identify a simple method for evaluating
      respiratory function using complete blood count parameters. METHODS: The complete
      blood count parameters, including red blood cell (RBC) count, hemoglobin (Hb)
      level, lymphocyte (Lym) and platelet (Plt) count, and partial pressure of oxygen
      (PO2 ) level, were measured using automated analyzers in patients with chronic
      obstructive pulmonary disease (COPD), aged subjects, and young subjects (control
      group). The red cell index (RCI) was calculated using the following equation:
      (RBC * Hb)/(Lym * Plt); in theory, the RCI is inversely proportional to the
      respiratory function. RESULTS: We observed a significant relationship between the
      RCI and PCO2 values, and between the RCI and FEV1/FVC values (P < .05). The RCI
      in the COPD, and aged subject groups were all significantly higher than that in
      the control group (P < .05). The cutoff value for normal respiratory function was
      2.3. The positive rates for an abnormal increase in RCI were also considerably
      higher in each observation group than in the control group (P < .05). CONCLUSION:
      The RCI can be considered as a simple and effective tool for evaluating
      respiratory function.

PMID- 29333621
TI  - Characterization of mouse neuro-urological dynamics in a novel decerebrate
      arterially perfused mouse (DAPM) preparation.
AB  - AIM: To develop the decerebrate arterially perfused mouse (DAPM) preparation, a
      novel voiding model of the lower urinary tract (LUT) that enables in vitro-like
      access with in vivo-like neural connectivity. METHODS: Adult male mice were
      decerebrated and arterially perfused with a carbogenated, Ringer's solution to
      establish the DAPM. To allow distinction between central and peripheral actions
      of interventions, experiments were conducted in both the DAPM and in a "pithed"
      DAPM which has no brainstem or spinal cord control. RESULTS: Functional
      micturition cycles were observed in response to bladder filling. During each
      void, the bladder showed strong contractions and the external urethral sphincter
      (EUS) showed bursting activity. Both the frequency and amplitude of non-voiding
      contractions (NVCs) in DAPM and putative micromotions (pMM) in pithed DAPM
      increased with bladder filling. Vasopressin (>400 pM) caused dyssynergy of the
      LUT resulting in retention in DAPM as it increased tonic EUS activity and basal
      bladder pressure in a dose-dependent manner (basal pressure increase also noted
      in pithed DAPM). Both neuromuscular blockade (vecuronium) and autonomic ganglion
      blockade (hexamethonium), initially caused incomplete voiding, and both drugs
      eventually stopped voiding in DAPM. Intravesical acetic acid (0.2%) decreased the
      micturition interval. Recordings from the pelvic nerve in the pithed DAPM showed
      bladder distention-induced activity in the non-noxious range which was associated
      with pMM. CONCLUSIONS: This study demonstrates the utility of the DAPM which
      allows a detailed characterization of LUT function in mice.

PMID- 29333622
TI  - Metabolic acidosis and anaemia associated with dorzolamide in a patient with
      impaired renal function.
AB  - Topical carbonic anhydrase inhibitors (CAI), used for treatment of glaucoma, are
      generally regarded as safe and unconnected with systemic side effects. We report
      an unusual case of fatigue, metabolic acidosis, and normocytic anaemia associated
      with ocular administration of the CAI, dorzolamide, in a patient with impaired
      renal function. In chronic kidney disease, where CAI elimination may be
      decreased, and patients prone to develop metabolic acidosis, systemic absorption
      of ocular administered CAI could lead to rare, but potentially serious adverse
      reaction, that are a consequence of inhibition of extraocular carbonic anhydrase
      isoenzymes.

PMID- 29333624
TI  - Turning fifty: join the FEBS Letters anniversary celebrations!: The FEBS Letters
      Editorial Team.

PMID- 29333623
TI  - Evaluation of universal immunohistochemical screening of sebaceous neoplasms in a
      service setting.
AB  - BACKGROUND: Muir-Torre syndrome (MTS) is a subtype of Lynch syndrome, which
      encompasses the combination of sebaceous skin tumours or keratoacanthomas and
      internal malignancy, due to mutations in DNA mismatch repair genes. Sebaceous
      neoplasms (SNs) may occur before other malignancies, and may lead to the
      diagnosis, which allows testing of other family members, cancer surveillance,
      risk-reducing surgery or prevention therapies. AIM: To evaluate the efficacy of
      universal immunohistochemistry (IHC) screening of SNs in a service setting.
      METHODS: Patients with SNs were ascertained by a regional clinical pathology
      service over a 3-year period. Results of tumour IHC, clinical genetics notes and
      germline genetic testing were retrospectively reviewed. RESULTS: In total, 62
      patients presented with 71 SNs; 9 (15%) of these patients had previously
      diagnosed MTS. Tumour IHC was performed for 50 of the 53 remaining patients
      (94%); 26 (52%) had loss of staining of one or more mismatch repair proteins.
      Fifteen patients were referred to the Clinical Genetics department, and 10
      patients underwent germline genetic testing. Two had a new diagnosis of MTS
      confirmed, with heterozygous pathogenic mutations detected in the MSH2 and PMS2
      genes (diagnostic yield 20%). The PMS2 mutation was identified in a 57-year-old
      woman with a sebaceous adenoma and history of endometrial cancer; to our
      knowledge, this is the first time a PMS2 mutation has been reported in MTS.
      CONCLUSIONS: Universal IHC screening of SNs is an effective method to identify
      cases for further genetic evaluation. Rates of referral to clinical genetics were
      only moderate (58%). Increased awareness of MTS could help improve the rate of
      onward referral.

PMID- 29333625
TI  - K3 Li3 Gd7 (BO3 )9 : A New Gadolinium-Rich Orthoborate for Cryogenic Magnetic
      Cooling.
AB  - Magnetic cooling technology based on magnetocaloric effect (MCE) has attracted
      great interest in obtaining extremely low temperatures, for example, for space
      exploration. Here, we grew a new gadolinium-rich orthoborate K3 Li3 Gd7 (BO3 )9
      (1) as a promising cryogenic magnetic coolant. It exhibits a complicated three
      dimensional framework constructed from BO3 groups and gadolinium-oxygen chains.
      The Gd-O chain consists of two types of clusters of Gd3 O20 and Gd3 O19
      interconnection by Gd(4)O8 polyhydron. Due to its high gadolinium concentration,
      a large -DeltaSm of 56.6 J kg-1  K-1 for 1 was obtained at 2 K and DeltaH=7 T,
      much larger than that of the commercial benchmark Gd3 Ga5 O12 (GGG) crystal (38.4
      J kg-1  K-1 ), suggesting it to be an excellent MCE material.

PMID- 29333626
TI  - Effect of astaxanthin on the quality of boar sperm stored at 17 degrees C,
      incubated at 37 degrees C or under in vitro conditions.
AB  - The aim of the study was to investigate the effect of the antioxidant astaxanthin
      on boar semen. Twenty ejaculates from 10 boars (two ejaculates/boar) were
      extended and split in three groups: semen control (SC), solvent control (C; semen
      with dimethyl sulfoxide, the diluent of astaxanthin) and semen with astaxanthin
      (A) in concentration 0.5 MUmol/L. Sperm quality parameters (motility and
      kinetics, morphology, viability, functional integrity of sperm plasma membrane by
      Hypo-Osmotic Swelling Test [HOST] and DNA integrity) were assessed at 0, 24 and
      48 hr of storage at 17 degrees C (experiment I), before (0 hr) and after (1 hr)
      of sperm thermal resistance assay at 37 degrees C (experiment II) and finally
      before (0 hr) and after (1 hr) sperm in vitro incubation (38.5 degrees C, 5% CO2
      , maximum humidity [experiment III]). In experiment I, group A performed overall
      better than group SC and as a tendency better than group C regarding viability.
      Total motility, rapid spermatozoa and HOST remained constant across time in group
      A, whereas they decreased in the remaining groups. In experiment II, regarding
      motility and viability, group A displayed better results across time than the
      other two groups. In experiment III, viability and total motility decreased in
      groups SC and C, while in group A, these parameters were not significantly
      different between the examination time points. In conclusion, astaxanthin has a
      beneficial and protective effect on boar semen quality under the investigated
      conditions.

PMID- 29333627
TI  - Saturable Absorption in 2D Ti3 C2 MXene Thin Films for Passive Photonic Diodes.
AB  - MXenes comprise a new class of 2D transition metal carbides, nitrides, and
      carbonitrides that exhibit unique light-matter interactions. Recently, 2D Ti3
      CNTx (Tx represents functional groups such as ?OH and ?F) was found to exhibit
      nonlinear saturable absorption (SA) or increased transmittance at higher light
      fluences, which is useful for mode locking in fiber-based femtosecond lasers.
      However, the fundamental origin and thickness dependence of SA behavior in MXenes
      remain to be understood. 2D Ti3 C2 Tx thin films of different thicknesses are
      fabricated using an interfacial film formation technique to systematically study
      their nonlinear optical properties. Using the open aperture Z-scan method, it is
      found that the SA behavior in Ti3 C2 Tx MXene arises from plasmon-induced
      increase in the ground state absorption at photon energies above the threshold
      for free carrier oscillations. The saturation fluence and modulation depth of Ti3
      C2 Tx MXene is observed to be dependent on the film thickness. Unlike other 2D
      materials, Ti3 C2 Tx is found to show higher threshold for light-induced damage
      with up to 50% increase in nonlinear transmittance. Lastly, building on the SA
      behavior of Ti3 C2 Tx MXenes, a Ti3 C2 Tx MXene-based photonic diode that breaks
      time-reversal symmetry to achieve nonreciprocal transmission of nanosecond laser
      pulses is demonstrated.

PMID- 29333628
TI  - Re(bpy)(CO)3 Cl Immobilized on Bipyridine-Periodic Mesoporous Organosilica for
      Photocatalytic CO2 Reduction.
AB  - This paper describes the physicochemical properties of a rhenium (Re) complex
      [Re(bpy)(CO)3 Cl] immobilized on a bipyridine-periodic mesoporous organosilica
      (BPy-PMO) acting as a solid support. The immobilized Re complex generated a metal
      to-ligand charge transfer absorption band at 400 nm. This wavelength is longer
      than that exhibited by Re(bpy)(CO)3 Cl in the polar solvent acetonitrile (371 nm)
      and is almost equal to that in nonpolar toluene (403 nm). The photocatalytic
      activity of this heterogeneous Re complex was lower than that of a homogeneous Re
      complex due to the reduced phosphorescence lifetime resulting from
      immobilization. However, the catalytic activity was enhanced by the co
      immobilization of the ruthenium (Ru) photosensitizer [Ru(bpy)3 ]2+ on the PMO
      pore surfaces. Quantum chemical calculations suggest that electron transfer
      between the Ru and Re complexes occurs through interactions between the molecular
      orbitals in the pore walls. These results should have applications to the design
      of efficient heterogeneous CO2 reduction photocatalysis systems.

PMID- 29333629
TI  - Surface Engineering for Extremely Enhanced Charge Separation and Photocatalytic
      Hydrogen Evolution on g-C3 N4.
AB  - Reinforcing the carrier separation is the key issue to maximize the
      photocatalytic hydrogen evolution (PHE) efficiency of graphitic carbon nitride (g
      C3 N4 ). By a surface engineering of gradual doping of graphited carbon rings
      within g-C3 N4 , suitable energy band structures and built-in electric fields are
      established. Photoinduced electrons and holes are impelled into diverse
      directions, leading to a 21-fold improvement in the PHE rate.

PMID- 29333630
TI  - Efficient Supercapacitor Energy Storage Using Conjugated Microporous Polymer
      Networks Synthesized from Buchwald-Hartwig Coupling.
AB  - Supercapacitors have received increasing interest as energy storage devices due
      to their rapid charge-discharge rates, high power densities, and high durability.
      In this work, novel conjugated microporous polymer (CMP) networks are presented
      for supercapacitor energy storage, namely 3D polyaminoanthraquinone (PAQ)
      networks synthesized via Buchwald-Hartwig coupling between 2,6
      diaminoanthraquinone and aryl bromides. PAQs exhibit surface areas up to 600 m2 g
      1 , good dispersibility in polar solvents, and can be processed to flexible
      electrodes. The PAQs exhibit a three-electrode specific capacitance of 576 F g-1
      in 0.5 m H2 SO4 at a current of 1 A g-1 retaining 80-85% capacitances and nearly
      100% Coulombic efficiencies (95-98%) upon 6000 cycles at a current density of 2 A
      g-1 . Asymmetric two-electrode supercapacitors assembled by PAQs show a
      capacitance of 168 F g-1 of total electrode materials, an energy density of 60 Wh
      kg-1 at a power density of 1300 W kg-1 , and a wide working potential window (0
      1.6 V). The asymmetric supercapacitors show Coulombic efficiencies up to 97% and
      can retain 95.5% of initial capacitance undergo 2000 cycles. This work thus
      presents novel promising CMP networks for charge energy storage.

PMID- 29333631
TI  - Is ejection fraction in heart failure a limitation or an opportunity?

PMID- 29333632
TI  - Binding of Cu+ and Cu2+ with peptides: Peptides = oxytocin, Arg8 -vasopressin,
      bradykinin, angiotensin-I, substance-P, somatostatin, and neurotensin.
AB  - The intrinsic binding ability of 7 natural peptides (oxytocin, arg8 -vasopressin,
      bradykinin, angiotensin-I, substance-P, somatostatin, and neurotensin) with
      copper in 2 different oxidation states (CuI/II ) derived from different Cu+/2+
      precursor sources have been investigated for their charge-dependent binding
      characteristics. The peptide-CuI/II complexes, [M - (n-1)H + nCuI ] and [M - (2n
      1)H + nCuII ], are prepared/generated by the reaction of peptides with CuI
      solution/Cu-target and CuSO4 solution and are analyzed by using matrix-assisted
      laser desorption/ionization (MALDI) time-of-flight mass spectrometry. The MALDI
      mass spectra of both [M - (n-1)H + nCuI ] and [M - (2n-1)H + nCuII ] complexes
      show no mass shift due to the loss of ?H atoms in the main chain ?NH of these
      peptides by Cu+ and Cu2+ deprotonation. The measured m/z value indicates the
      reduction of CuI/II oxidation state into Cu0 during MALDI processes. The number
      and relative abundance of Cu+ bound to the peptides are greater compared with the
      Cu2+ bound peptides. Oxytocin, arg8 -vasopressin, bradykinin, substance-P, and
      somatostatin show the binding of 5Cu+ , and angiotensin-I and neurotensin show
      the binding of 7Cu+ from both CuI and Cu targets, while bradykinin shows the
      binding of 2Cu2+ , oxytocin, arg8 -vasopressin, angiotensin-I, and substance-P;
      somatostatin shows the binding of 3Cu2+ ; and neurotensin shows 4Cu2+ binding.
      The binding of more Cu+ with these small peptides signifies that the bonding
      characteristics of both Cu+ and Cu2+ are different. The amino acid residues
      responsible for the binding of both Cu+ and Cu2+ in these peptides have been
      identified based on the density functional theory computed binding energy values
      of Cu+ and the fragment transformation method predicted binding preference of
      Cu2+ for individual amino acids.

PMID- 29333633
TI  - Long-term outcome of stereotactic body radiotherapy for patients with small
      hepatocellular carcinoma.
AB  - AIM: To evaluate the long-term outcome of stereotactic body radiotherapy in
      patients with small hepatocellular carcinoma who were ineligible for resection or
      ablation therapies. METHODS: A total of 65 patients with 74 hepatocellular
      carcinomas (median tumor size 16 mm) were enrolled in the present study. They
      were treated with the prescribed dose of 48 Gy in four fractions at the
      isocenter. We extended the observation period and analyzed long-term outcomes,
      including overall survival, progression-free survival, local control, and various
      prognostic factors, in these patients. RESULTS: The median follow-up period was
      41 months for all patients and 62 months for surviving patients. The 3- and 5
      year overall survival rates were 56.3% (95% confidence interval, 44.1-68.5%) and
      41.4% (95% confidence interval, 28.7-54.1%), respectively. The 3- and 5-year
      progression-free survival rates were 25.4% (95% confidence interval, 14.0-36.8%)
      and 10.6% (95% confidence interval, 1.5-19.8%), respectively. The 3- and 5-year
      local control rates were both 100% (95% confidence interval 100%). Liver
      toxicities exceeding grade 3 were observed in 15 patients (23.1%). The proportion
      of patients who had grade >=3 toxicities did not increase. Adverse effects (grade
      <=2) presented as significant prognostic factors of overall survival, while TNM
      stage (T1N0M0) was a significant prognostic factor of progression-free survival
      after multivariate analysis. CONCLUSIONS: Stereotactic body radiotherapy was
      effective for patients with small hepatocellular carcinomas who were ineligible
      for resection or ablation therapies. The incidence of grade >=3 adverse effects
      did not increase, even after longer follow-up times.

PMID- 29333634
TI  - Euthanasia and the nature of suffering in addiction.

PMID- 29333635
TI  - The changing relationship between bronchopulmonary dysplasia and cognition in
      very preterm infants.
AB  - AIM: To characterise the relationship between bronchopulmonary dysplasia (BPD)
      severity and cognition in the post-surfactant era. METHODS: This was a single
      centre retrospective analysis of a cohort of infants born 2009-2012. Inclusion
      criteria were as follows: admission within 48 hours of birth, gestational age 22
      0/7-31-6/7 weeks, birthweight 400-1500 g and Bayley Scales of Infant and Toddler
      Development-III testing at 18-26 months corrected age. Infants (n = 151) were
      classified by BPD severity with the NIH Workshop definition. Generalised linear
      modelling and multivariate logistic regression were performed. RESULTS: Bayley
      cognitive score was not associated with BPD severity in univariate (p = 0.053) or
      multivariate (p = 0.503) analysis. About 27% of infants with no/mild BPD, 33% of
      infants with moderate BPD and 40% of infants with severe BPD had a cognitive
      score <85. There was no difference in the odds of cognitive score <85 based on
      BPD severity in univariate (p = 0.485) or multivariate analysis (p = 0.225). All
      infants with cognitive score <70 had severe BPD, although the association between
      cognitive score <70 and BPD severity was not significant. CONCLUSION: We found no
      independent effect of BPD severity level on cognition. The likelihood of a
      cognitive score <85 was not associated with BPD severity.

PMID- 29333636
TI  - In search of markers of pulmonary vascular remodelling in pulmonary hypertension
      due to left heart disease.

PMID- 29333638
TI  - Rapid profiling of polymeric phenolic acids in Salvia miltiorrhiza by hybrid data
      dependent/targeted multistage mass spectrometry acquisition based on expected
      compounds prediction and fragment ion searching.
AB  - Phenolic acids are the major water-soluble components in Salvia miltiorrhiza
      (>5%). According to previous studies, many of them contribute to the
      cardiovascular effects and antioxidant effects of S. miltiorrhiza. Polymeric
      phenolic acids can be considered as the tanshinol derived metabolites, e.g.,
      dimmers, trimers, and tetramers. A strategy combined with tanshinol-based
      expected compounds prediction, total ion chromatogram filtering, fragment ion
      searching, and parent list-based multistage mass spectrometry acquisition by
      linear trap quadropole-orbitrap Velos mass spectrometry was proposed to rapid
      profile polymeric phenolic acids in S. miltiorrhiza. More than 480 potential
      polymeric phenolic acids could be screened out by this strategy. Based on the
      fragment information obtained by parent list-activated data dependent multistage
      mass spectrometry acquisition, 190 polymeric phenolic acids were characterized by
      comparing their mass information with literature data, and 18 of them were
      firstly detected from S. miltiorrhiza. Seven potential compounds were tentatively
      characterized as new polymeric phenolic acids from S. miltiorrhiza. This strategy
      facilitates identification of polymeric phenolic acids in complex matrix with
      both selectivity and sensitivity, which could be expanded for rapid discovery and
      identification of compounds from complex matrix.

PMID- 29333637
TI  - Increased free Zn2+ correlates induction of sarco(endo)plasmic reticulum stress
      via altered expression levels of Zn2+ -transporters in heart failure.
AB  - Zn2+ -homoeostasis including free Zn2+ ([Zn2+ ]i ) is regulated through Zn2+ 
      transporters and their comprehensive understanding may be important due to their
      contributions to cardiac dysfunction. Herein, we aimed to examine a possible role
      of Zn2+ -transporters in the development of heart failure (HF) via induction of
      ER stress. We first showed localizations of ZIP8, ZIP14 and ZnT8 to both
      sarcolemma and S(E)R in ventricular cardiomyocytes (H9c2 cells) using confocal
      together with calculated Pearson's coefficients. The expressions of ZIP14 and
      ZnT8 were significantly increased with decreased ZIP8 level in HF. Moreover,
      [Zn2+ ]i was significantly high in doxorubicin-treated H9c2 cells compared to
      their controls. We found elevated levels of ER stress markers, GRP78 and
      CHOP/Gadd153, confirming the existence of ER stress. Furthermore, we measured
      markedly increased total PKC and PKCalpha expression and PKCalpha-phosphorylation
      in HF. A PKC inhibition induced significant decrease in expressions of these ER
      stress markers compared to controls. Interestingly, direct increase in [Zn2+ ]i
      using zinc-ionophore induced significant increase in these markers. On the other
      hand, when we induced ER stress directly with tunicamycin, we could not observe
      any effect on expression levels of these Zn2+ transporters. Additionally,
      increased [Zn2+ ]i could induce marked activation of PKCalpha. Moreover, we
      observed marked decrease in [Zn2+ ]i under PKC inhibition in H9c2 cells. Overall,
      our present data suggest possible role of Zn2+ transporters on an intersection
      pathway with increased [Zn2+ ]i and PKCalpha activation and induction of HF, most
      probably via development of ER stress. Therefore, our present data provide novel
      information how a well-controlled [Zn2+ ]i via Zn2+ transporters and PKCalpha can
      be important therapeutic approach in prevention/treatment of HF.

PMID- 29333639
TI  - Decreasing deceased donor transplant rates among children (<=6 years) under the
      new kidney allocation system.
AB  - The Kidney Allocation System (KAS) was implemented in December 2014 with unknown
      impact on the pediatric waitlist. To understand the effect of KAS on pediatric
      registrants, deceased donor kidney transplant (DDKT) rate was assessed using
      interrupted time series analysis and time-to-event analysis. Two allocation eras
      were defined with an intermediary washout period: Era 1 (01/01/2013-09/01/2014),
      Era 2 (09/01/2014-03/01/2015), and Era 3(03/01/2015-03/01/2017). When using Cox
      proportional hazards, there was no significant association between allocation era
      and DDKT likelihood as compared to Era 1 (Era 3: aHR: 1.07, 95% CI: 0.97-1.18, P
      = .17). However, this was not consistent across all subgroups. Specifically,
      while highly sensitized pediatric registrants were consistently less likely to be
      transplanted than their less sensitized counterparts, this disparity was
      attenuated in Era 3 (Era 1 aHR: 0.04, 95%CI: 0.01-0.14, P < .001; Era 3 aHR:
      0.33, 95% CI: 0.21-0.53, P < .001) whereas the youngest registrants aged 0-6
      experienced a 21% decrease in DDKT likelihood in Era 3 as compared to Era 1 (aHR:
      0.79, 95% CI: 0.64-0.98, P = .03). Thus, while overall DDKT likelihood remained
      stable with the introduction of KAS, registrants <= 6 years of age were
      disadvantaged, warranting further study to ensure equitable access to
      transplantation.

PMID- 29333640
TI  - Comparing Mental Health of US Children of Immigrants and Non-Immigrants in 4
      Racial/Ethnic Groups.
AB  - BACKGROUND: To compare the mental health status of children of immigrant (COI)
      and non-immigrant (NI) parents and to determine whether differences in mental
      health status between COI and NI vary across 4 racial/ethnic groups. METHODS: We
      conducted universal mental health screening of 2374 sixth graders in an urban
      public school district. To screen, we administered well-validated adolescent
      depression and disruptive behavior problem questionnaires. We evaluated
      associations between child mental health, parent immigration status, and
      race/ethnicity using binomial regression. RESULTS: Among Asian American/Pacific
      Islanders and Latinos, COI had significantly higher depression and disruptive
      behavior scores compared to NI. For Blacks/African Americans, children of NI
      parents had significantly higher disruptive behavior scores compared to COI. For
      European Americans, scores of COI and NI did not differ and were relatively low.
      CONCLUSION: Our study suggests that how the emotional health of COI is faring
      relative to children of NI depends on the child's race/ethnicity.

PMID- 29333641
TI  - Who Eats School Breakfast? Parent Perceptions of School Breakfast in a State With
      Very Low Participation.
AB  - BACKGROUND: Having breakfast is correlated with health and academic benefits;
      yet, many children do not consume breakfast, and participation in the federal
      School Breakfast Program remains low. The purpose of this study was to examine
      parent perceptions of school breakfast and identify relationships between those
      who consume breakfast at school and those who do not. METHODS: A random sample of
      100 schools, representing 29 school districts, across the state of Utah was
      selected to participate in the survey. Administrators were asked to distribute an
      online survey link to the parents of their school. Parents answered questions
      about their oldest kindergarten through 12th grade child. Qualitative and
      quantitative analyses were performed. RESULTS: A total of 488 parents completed
      the survey. In a multilevel model, child grade level, participation in free and
      reduced-price lunch, and perceive benefits to school breakfast were significantly
      related to eating breakfast at school. Some major themes from the qualitative
      analysis included no need for school breakfast, perception of regional values,
      and logistical issues. CONCLUSIONS: Parent perception of school meals is related
      to participation. This study identifies several areas of perception that could be
      address through parent education to increase school breakfast participation.

PMID- 29333642
TI  - Early Adolescents' Emotional Well-Being in the Classroom: The Role of Personal
      and Contextual Assets.
AB  - BACKGROUND: The objective was to predict early adolescents' emotional well-being
      from personal and contextual assets in the classroom. Emotional well-being is a
      key indicator of health. Aligned with the positive youth development (PYD)
      framework, a supportive classroom environment and positive relationships with
      teachers and peers were contextual assets in the present study; positive self
      concept was a personal asset. METHODS: The sample was 406 grade 4 to 7 public
      elementary school students from diverse backgrounds (mean = 11.27 years; SD =
      0.89; 50% female). Data were self-, teacher-, and peer-reported. Structural
      equation modeling (SEM) analyses were used to evaluate model fit and identify
      significant pathways. RESULTS: SEM indicated a good model fit. Overall, 68% of
      variability in early adolescents' emotional well-being was explained. Positive
      self-concept directly predicted emotional well-being. Supportive classroom
      environment predicted emotional well-being directly and indirectly through
      increases in positive social relationships and self-concept. Positive social
      relationships predicted well-being only indirectly through positive self-concept.
      CONCLUSIONS: Contextual and personal assets are central for early adolescents'
      emotional well-being. The interrelation among assets needs to be considered when
      understanding, and ultimately promoting students' emotional well-being. The
      present findings extend previous research and inform school-based intervention
      and prevention programming and teacher professional development.

PMID- 29333643
TI  - Race, Sex, and Discrimination in School Settings: A Multilevel Analysis of
      Associations With Delinquency.
AB  - BACKGROUND: Adolescence is a critical phase of development and experimentation
      with delinquent behaviors. There is a growing body of literature exploring
      individual and structural impacts of discrimination on health outcomes and
      delinquent behaviors. However, there is limited research assessing how school
      diversity and discrimination impact students' delinquent behaviors. In response,
      the purpose of this study was to assess if individual- and school-level
      indicators of discrimination and diversity were associated with student
      delinquent behaviors among African American and White students. METHODS: We
      analyzed Wave I (1994-1995) data from the National Longitudinal Study of
      Adolescent Health. Our analysis was limited to 8947 African American and White
      students (73% White, 48% male, and 88% parent >= high school education). We used
      multilevel zero-inflated negative binomial regression to test the association of
      individual- and school characteristics and discrimination with the number of self
      reported delinquent behaviors. RESULTS: Race, sex, perceived peer inclusion, and
      teacher discrimination were predictors of students' delinquent behaviors. The
      average school perceived peer inclusion and percentage of African Americans in
      teaching roles were associated with delinquent behaviors. CONCLUSIONS: Findings
      from this study highlight the potential for intervention at the interpersonal and
      school levels to reduce delinquency among African American and White students.

PMID- 29333644
TI  - School Lunch Consumption Among 3 Food Service Providers in New Orleans.
AB  - BACKGROUND: Louisiana has one of the highest rates of overweight and obese
      children in the United States. The Healthy School Food Collaborative (HSFC) was
      created to allow New Orleans's schools to select their own healthy school Food
      Service Provider (FSP) with requirements for higher nutritional standards than
      traditional options. The goal of this cross-sectional study was to examine
      whether HSFC membership was associated with lunch consumption rates in elementary
      school children. METHODS: An 8-week plate waste study examining 18,070 trays of
      food among fourth and fifth graders was conducted. Participants included 7
      schools and the 3 FSPs (2 HSFC and 1 non-HSFC member) that serviced them. Mixed
      models analysis examined whether consumption rates of food items differed among
      FSPs. RESULTS: On average, students consumed 307 cal during lunch. Analyses
      showed significant differences in consumption rates of entree, vegetables, fruit,
      and milk between the 3 FSPs (p < .01). The highest consumption rate was among
      entrees at 65%. One HSFC provider had consumption levels consistent with the non
      HSFC FSP. CONCLUSIONS: Overall, students consumed less than 60% of the US
      Department of Agriculture recommended calories for school lunch. While overall
      caloric consumption was higher among the non-HSFC schools, interventions to
      increase lunch consumption across all schools are needed.

PMID- 29333645
TI  - How Healthy Is Homeschool? An Analysis of Body Composition and Cardiovascular
      Disease Risk.
AB  - BACKGROUND: Public school children regularly participate in school-based physical
      activity, physical education, and fitness testing. However, almost 2 million
      American children are homeschooled. The purpose of this research was to assess
      the body composition of elementary school-aged homeschool children and their
      corresponding cardiovascular disease (CVD) risk. METHODS: This research explored
      the body composition and CVD risk of 145 homeschool children aged 5-11 years
      using body mass index (BMI), percent body fat, and waist circumference. Chi
      square and Mann-Whitney U tests examined differences in CVD risk within the
      homeschool population. RESULTS: Overall, homeschool children had average BMI z
      scores (SD [range]) with a mean of -0.11 (0.97 [-3.47 to 2.53]). Unhealthy
      classifications were seen in 11.2% of the sample by BMI, 19.6% by percent body
      fat, and 49.7% by waist circumference. Statistical analysis revealed no
      difference in CVD risk between sexes (chi2 (1) = 0.062, p = .804) or ethnicities
      (chi2 (1) = 0.927, p = .336) but increased prevalence in children aged 5-9 years
      (U = 1427, z = -4.559, p < .001). CONCLUSIONS: Almost half of elementary school
      aged homeschool children showed increased risk for CVD and need regular
      assessment of central adiposity.

PMID- 29333646
TI  - Examining Predictors of Breakfast Skipping and Breakfast Program Use Among
      Secondary School Students in the COMPASS Study.
AB  - BACKGROUND: Many Canadian schools offer breakfast programs; however, students'
      engagement in these programs is low, while breakfast skipping is highly prevalent
      among youth. This study examined whether the availability of breakfast programs
      supports adolescents' regular breakfast eating, and identified characteristics of
      breakfast skippers who are not using these programs. METHODS: Data from 30,771
      secondary school students from Ontario and Alberta, Canada, participating in Year
      3 (2014-2015) of the COMPASS study were used for descriptive and logistic
      regression analyses. Participants were categorized by self-reported breakfast
      eating and school breakfast program use. RESULTS: Sixteen percent of participants
      reported using school breakfast programs. Breakfast skipping was highly prevalent
      among participants, regardless of their breakfast program use. Characteristics
      significantly associated with program use included traveling to school via public
      transit or a school bus, being a bullying victim, and having a high school
      connectedness score. A desire to lose weight and non-involvement in school sports
      were significantly associated with being a "breakfast skipper/nonprogram user."
      CONCLUSIONS: School breakfast programs do not consistently support regular
      breakfast eating, even among adolescents actively engaged in these programs.
      Future research should identify and evaluate practices to bolster participation
      in breakfast programs and promote regular breakfast eating among adolescents.

PMID- 29333647
TI  - Effect of Sleep Duration, Diet, and Physical Activity on Obesity and Overweight
      Elementary School Students in Shanghai.
AB  - BACKGROUND: This was a cross-sectional survey to investigate the relationship of
      age, parent education, sleep duration, physical activity, and dietary habits with
      overweight or obesity in school-age children in Shanghai. METHODS: The survey
      gathered information from 13,001 children in grades 1 through 5 (age 6 to 10
      years) among 26 elementary schools in 7 districts. Activity level was evaluated
      using the International Children's Leisure Activities Study Survey Questionnaire
      (CLASS-C). The definitions of normal, overweight, and obese were adjusted for
      each age. RESULTS: Logistic regression analysis indicated that age, being male,
      having <=10 hours of sleep on non-school days, eating >=1 vegetable/day, or
      drinking >=1 sugar-sweetened drink/day increased the risk for a child being
      overweight or obese compared with having >10 hours of sleep or <=3 vegetables or
      <=3 sugar-sweetened drinks/month (p <= .008). Having >2 hours of outdoor
      activities on non-school days reduced the risk of being overweight or obese
      compared with <=2 hours of outdoor activities on non-school days (p < .001).
      CONCLUSIONS: We found that age, sex, sleep, and some dietary habits impacted
      weight, and suggests that specific cultural and economic factors may impact risk
      of a child being overweight or obese.

PMID- 29333648
TI  - Physical and Social Contexts of Physical Activity Behaviors of Fifth and Seventh
      Grade Youth.
AB  - BACKGROUND: The purpose of this study was to characterize the temporal, social,
      and physical contexts for physical activities commonly reported in a diverse
      cohort of 753 boys and girls from fifth to seventh grade. METHODS: Data were
      obtained from a multilevel longitudinal study, the Transitions and Activity
      Changes in Kids. The Physical Activity Choices instrument assessed previous 5-day
      participation in specific physical activities and their temporal, social, and
      physical contexts. Mixed model repeated measure analyses of variance and
      multinomial analyses examined sex differences and change over time. RESULTS:
      Fifth grade boys and girls reported participation in similar activities at
      similar frequencies, which declined significantly by seventh grade. One temporal
      pattern, playing with younger children, changed over time from "both
      inside/outside" to "outside" school. Boys and females reported more activities
      performed in class/team groups over time. Most activities took place primarily at
      home for all participants in both grades. CONCLUSIONS: Boys and girls reported
      declines in the variety and frequency of activities from fifth to seventh grade.
      There were sex-specific patterns in physical activities and groups; however, all
      participants reported home as the primary location and a shift to class/team
      groups over time. Schools are well-positioned to provide additional physical
      activity opportunities.

PMID- 29333649
TI  - Detection of gene-environment interactions in a family-based population using
      SCAD.

PMID- 29333650
TI  - Comments on "Longitudinal beta-binomial modeling using GEE for overdispersed
      binomial data".

PMID- 29333651
TI  - Corrigendum.

PMID- 29333652
TI  - Establishment and characterization of a brain-cell line from kelp grouper
      Epinephelus moara.
AB  - A new brain-cell line, EMB, was developed from kelp grouper Epinephelus moara, a
      cultured marine fish. The EMB cells were subcultured for more than 60 passages.
      The cells were cultured in Leibovitz's L-15 medium (L15) supplemented with
      antibiotics, foetal bovine serum (FBS), 2-mercaptoethanol (2-ME) and basic
      fibroblast growth factor (bFGF). The cells could grow at 18-30 degrees  C, with
      the maximum growth between 24 and 30 degrees  C. The optimum FBS concentration
      for the cells growth ranged between 15 and 20%. Chromosome analysis indicated
      that the modal chromosome number was 48 in the cells at passage 45. After being
      transfected with pEGFP-N3 plasmid, the cells could successfully express green
      fluorescence protein (GFP), implying that this cell line can be used for
      transgenic studies. A significant cytopathic effect (CPE) was observed in the
      cells after infection with Singapore grouper iridovirus (SGIV) or red spotted
      grouper nervous necrosis virus (RGNNV) and the viral replication was confirmed by
      quantitative real-time PCR (qrt-PCR) assay, which suggested EMB's application
      potential for studies of SGIV and RGNNV.

PMID- 29333654
TI  - Corrigendum.

PMID- 29333653
TI  - Vitiligo-like lesions and immune checkpoint inhibition therapy: is it truly an
      adverse event exclusive to patients with melanoma?

PMID- 29333655
TI  - Preparation of High-Percentage 1T-Phase Transition Metal Dichalcogenide Nanodots
      for Electrochemical Hydrogen Evolution.
AB  - Nanostructured transition metal dichalcogenides (TMDs) are proven to be efficient
      and robust earth-abundant electrocatalysts to potentially replace precious
      platinum-based catalysts for the hydrogen evolution reaction (HER). However, the
      catalytic efficiency of reported TMD catalysts is still limited by their low
      density active sites, low conductivity, and/or uncleaned surface. Herein, a
      general and facile method is reported for high-yield, large-scale production of
      water-dispersed, ultrasmall-sized, high-percentage 1T-phase, single-layer TMD
      nanodots with high-density active edge sites and clean surface, including MoS2 ,
      WS2 , MoSe2 , Mo0.5 W0.5 S2 , and MoSSe, which exhibit much enhanced
      electrochemical HER performances as compared to their corresponding nanosheets.
      Impressively, the obtained MoSSe nanodots achieve a low overpotential of -140 mV
      at current density of 10 mA cm-2 , a Tafel slope of 40 mV dec-1 , and excellent
      long-term durability. The experimental and theoretical results suggest that the
      excellent catalytic activity of MoSSe nanodots is attributed to the high-density
      active edge sites, high-percentage metallic 1T phase, alloying effect and basal
      plane Se-vacancy. This work provides a universal and effective way toward the
      synthesis of TMD nanostructures with abundant active sites for electrocatalysis,
      which can also be used for other applications such as batteries, sensors, and
      bioimaging.

PMID- 29333656
TI  - First case of Stevens-Johnson syndrome after rabies vaccination.
AB  - We describe the first case of Stevens-Johnson syndrome (SJS) occurring 8 days
      after the first dose of a three-dose rabies vaccination series. She had no
      history of vaccine-related rash or other adverse drug reactions, nor had she
      received any other drug therapy. The temporal relationship between the
      development of SJS and the vaccination suggests that the rabies vaccination
      probably was the causal agent. This case serves as a warning of a distinct
      cutaneous reaction of rabies vaccination.

PMID- 29333657
TI  - Gelatin Methacryloyl Hydrogels in the Absence of a Crosslinker as 3D Glioblastoma
      Multiforme (GBM)-Mimetic Microenvironment.
AB  - 3D platforms are important for monitoring tumor progression and screening drug
      candidates to eradicate tumors such as glioblastoma multiforme (GBM), a malignant
      type of human brain tumor. Here, a new strategy is reported that exploits visible
      light-induced crosslinking of gelatin where the reaction is carried out in the
      absence of an additional crosslinker. Visible light-induced crosslinking promotes
      the design of cancer microenvironment-mimetic system without compromising the
      cell viability during the process and absence of crosslinker facilitates the
      synthesis of the unique construct. Suspension and spheroid-based models of GBM
      are used to investigate cellular behavior, expression profiles of malignancy, and
      apoptosis-related genes within this unique network. Furthermore, sensitivity to
      an anticancer drug, Digitoxigenin, treatment is investigated in detail. The data
      suggest that U373 cells, in sparse or spheroid form, have significantly decreased
      expressions of apoptosis-activating genes, Bad, Puma, and Caspase-3, and a high
      expression of prosurvival Bcl-2 gene within GelMA hydrogels. Matrix
      metalloproteinase genes are also upregulated within GelMA, suggesting positive
      contribution of gels on extracellular remodeling of cancer cells. This unique
      photocurable gelatin holds great potential for clinical translation of cancer
      research through the analysis of 3D malignant cancer cell behavior, and hence for
      more efficient treatment methods for GBM.

PMID- 29333659
TI  - Acute renal replacement therapy during hospitalization: Is training adequate?
AB  - Acute renal replacement therapy is one of the most common interventions provided
      by nephrologists, however, data on the quality of training provided to nephrology
      fellows is limited. Extensive curricula for acute renal replacement therapy and
      the management of poisonings and intoxications have been published, but personal
      experience suggests that there are significant opportunities to improve training.
      Particular areas to be considered include the use of novel technologies for
      assessment of volume status, greater emphasis on the dosing of medications during
      acute renal replacement therapy, greater training in assessing and tailoring
      treatment to the goals of care of the individual patient, incorporation of
      continuous quality improvement tools into the management of acute renal
      replacement therapy programs and development of robust simulation training to
      augment training.

PMID- 29333658
TI  - In Situ shRNA Synthesis on DNA-Polylactide Nanoparticles to Treat Multidrug
      Resistant Breast Cancer.
AB  - Nanomedicine has shown unprecedented potential for cancer theranostics. Nucleic
      acid (e.g., DNA and RNA) nanomedicines are of particular interest for combination
      therapy with chemotherapeutics. However, current nanotechnologies to construct
      such nucleic acid nanomedicines, which rely on chemical conjugation or physical
      complexation of nucleic acids with chemotherapeutics, have restrained their
      clinical translation due to limitations such as low drug loading efficiency and
      poor biostability. Herein, in situ rolling circle transcription (RCT) is applied
      to synthesize short hairpin RNA (shRNA) on amphiphilic DNA-polylactide (PLA)
      micelles. Core-shell PLA@poly-shRNA structures that codeliver a high payload of
      doxorubicin (Dox) and multidrug resistance protein 1 (MDR1) targeted shRNA for
      MDR breast cancer (BC) therapy are developed. DNA-PLA conjugates are first
      synthesized, which then self-assemble into amphiphilic DNA-PLA micelles; next,
      using the conjugated DNA as a promoter, poly-shRNA is synthesized on DNA-PLA
      micelles via RCT, generating PLA@poly-shRNA microflowers; and finally,
      microflowers are electrostatically condensed into nanoparticles using
      biocompatible and multifunctional poly(ethylene glycol)-grafted polypeptides (PPT
      g-PEG). These PLA@poly-shRNA@PPT-g-PEG nanoparticles are efficiently delivered
      into MDR breast cancer cells and accumulated in xenograft tumors, leading to MDR1
      silencing, intracellular Dox accumulation, potentiated apoptosis, and enhanced
      tumor therapeutic efficacy. Overall, this nanomedicine platform is promising to
      codeliver anticancer nucleic acid therapeutics and chemotherapeutics.

PMID- 29333660
TI  - Interventions to increase attendance for diabetic retinopathy screening.
AB  - BACKGROUND: Despite evidence supporting the effectiveness of diabetic retinopathy
      screening (DRS) in reducing the risk of sight loss, attendance for screening is
      consistently below recommended levels. OBJECTIVES: The primary objective of the
      review was to assess the effectiveness of quality improvement (QI) interventions
      that seek to increase attendance for DRS in people with type 1 and type 2
      diabetes.Secondary objectives were:To use validated taxonomies of QI intervention
      strategies and behaviour change techniques (BCTs) to code the description of
      interventions in the included studies and determine whether interventions that
      include particular QI strategies or component BCTs are more effective in
      increasing screening attendance;To explore heterogeneity in effect size within
      and between studies to identify potential explanatory factors for variability in
      effect size;To explore differential effects in subgroups to provide information
      on how equity of screening attendance could be improved;To critically appraise
      and summarise current evidence on the resource use, costs and cost effectiveness.
      SEARCH METHODS: We searched the Cochrane Library, MEDLINE, Embase, PsycINFO, Web
      of Science, ProQuest Family Health, OpenGrey, the ISRCTN, ClinicalTrials.gov, and
      the WHO ICTRP to identify randomised controlled trials (RCTs) that were designed
      to improve attendance for DRS or were evaluating general quality improvement (QI)
      strategies for diabetes care and reported the effect of the intervention on DRS
      attendance. We searched the resources on 13 February 2017. We did not use any
      date or language restrictions in the searches. SELECTION CRITERIA: We included
      RCTs that compared any QI intervention to usual care or a more intensive
      (stepped) intervention versus a less intensive intervention. DATA COLLECTION AND
      ANALYSIS: We coded the QI strategy using a modification of the taxonomy developed
      by Cochrane Effective Practice and Organisation of Care (EPOC) and BCTs using the
      BCT Taxonomy version 1 (BCTTv1). We used Place of residence,
      Race/ethnicity/culture/language, Occupation, Gender/sex, Religion, Education,
      Socioeconomic status, and Social capital (PROGRESS) elements to describe the
      characteristics of participants in the included studies that could have an impact
      on equity of access to health services.Two review authors independently extracted
      data. One review author entered the data into Review Manager 5 and a second
      review author checked them. Two review authors independently assessed risks of
      bias in the included studies and extracted data. We rated certainty of evidence
      using GRADE. MAIN RESULTS: We included 66 RCTs conducted predominantly (62%) in
      the USA. Overall we judged the trials to be at low or unclear risk of bias. QI
      strategies were multifaceted and targeted patients, healthcare professionals or
      healthcare systems. Fifty-six studies (329,164 participants) compared
      intervention versus usual care (median duration of follow-up 12 months). Overall,
      DRS attendance increased by 12% (risk difference (RD) 0.12, 95% confidence
      interval (CI) 0.10 to 0.14; low-certainty evidence) compared with usual care,
      with substantial heterogeneity in effect size. Both DRS-targeted (RD 0.17, 95% CI
      0.11 to 0.22) and general QI interventions (RD 0.12, 95% CI 0.09 to 0.15) were
      effective, particularly where baseline DRS attendance was low. All BCT
      combinations were associated with significant improvements, particularly in those
      with poor attendance. We found higher effect estimates in subgroup analyses for
      the BCTs 'goal setting (outcome)' (RD 0.26, 95% CI 0.16 to 0.36) and 'feedback on
      outcomes of behaviour' (RD 0.22, 95% CI 0.15 to 0.29) in interventions targeting
      patients, and 'restructuring the social environment' (RD 0.19, 95% CI 0.12 to
      0.26) and 'credible source' (RD 0.16, 95% CI 0.08 to 0.24) in interventions
      targeting healthcare professionals.Ten studies (23,715 participants) compared a
      more intensive (stepped) intervention versus a less intensive intervention. In
      these studies DRS attendance increased by 5% (RD 0.05, 95% CI 0.02 to 0.09;
      moderate-certainty evidence).Fourteen studies reporting any QI intervention
      compared to usual care included economic outcomes. However, only five of these
      were full economic evaluations. Overall, we found that there is insufficient
      evidence to draw robust conclusions about the relative cost effectiveness of the
      interventions compared to each other or against usual care.With the exception of
      gender and ethnicity, the characteristics of participants were poorly described
      in terms of PROGRESS elements. Seventeen studies (25.8%) were conducted in
      disadvantaged populations. No studies were carried out in low- or middle-income
      countries. AUTHORS' CONCLUSIONS: The results of this review provide evidence that
      QI interventions targeting patients, healthcare professionals or the healthcare
      system are associated with meaningful improvements in DRS attendance compared to
      usual care. There was no statistically significant difference between
      interventions specifically aimed at DRS and those which were part of a general QI
      strategy for improving diabetes care. This is a significant finding, due to the
      additional benefits of general QI interventions in terms of improving glycaemic
      control, vascular risk management and screening for other microvascular
      complications. It is likely that further (but smaller) improvements in DRS
      attendance can also be achieved by increasing the intensity of a particular QI
      component or adding further components.

PMID- 29333661
TI  - Nanocage-Therapeutics Prevailing Phagocytosis and Immunogenic Cell Death Awakens
      Immunity against Cancer.
AB  - A growing appreciation of the relationship between the immune system and the
      tumorigenesis has led to the development of strategies aimed at "re-editing" the
      immune system to kill tumors. Here, a novel tactic is reported for overcoming the
      activation-energy threshold of the immunosuppressive tumor microenvironment and
      mediating the delivery and presentation of tumor neoantigens to the host's immune
      system. This nature-derived nanocage not only efficiently presents ligands that
      enhance cancer cell phagocytosis, but also delivers drugs that induce immunogenic
      cancer cell death. The designed nanocage-therapeutics induce the release of
      neoantigens and danger signals in dying tumor cells, and leads to enhancement of
      tumor cell phagocytosis and cross-priming of tumor specific T cells by neoantigen
      peptide-loaded antigen-presenting cells. Potent inhibition of tumor growth and
      complete eradication of tumors is observed through systemic tumor-specific T cell
      responses in tumor draining lymph nodes and the spleen and further, infiltration
      of CD8+ T cells into the tumor site. Remarkably, after removal of the primary
      tumor, all mice treated with this nanocage-therapeutics are protected against
      subsequent challenge with the same tumor cells, suggesting development of
      lasting, tumor-specific responses. This designed nanocage-therapeutics "awakens"
      the host's immune system and provokes a durable systemic immune response against
      cancer.

PMID- 29333662
TI  - Serum levels of psoriasin (S100A7) and koebnerisin (S100A15) as potential markers
      of atherosclerosis in patients with psoriasis.
AB  - BACKGROUND: Psoriasin (S100A7) and koebnerisin (S100A15) are proinflammatory
      proteins upregulated in psoriasis, but their relation to atherosclerosis remains
      unclear. AIM: To evaluate the role of serum psoriasin and koebnerisin as possible
      markers for subclinical atherosclerosis in patients with psoriasis. METHODS:
      Serum levels of psoriasin and koebnerisin were measured by ELISA in 45 patients
      with psoriasis and in 45 healthy controls (HCs). Intima-media thickness (IMT) of
      the right and left common carotid arteries was measured to detect the presence of
      subclinical atherosclerosis. Clinical severity of psoriasis was estimated using
      the Psoriasis Area and Severity Index (PASI). RESULTS: Compared with HCs,
      patients with psoriasis had significantly higher levels of psoriasin (26.61 +/-
      22.45 ng/mL vs. 6.31 +/- 1.68 ng/mL, P < 0.001) and koebnerisin (21.2 +/- 13.12
      ng/mL vs. 12.2 +/- 4.67 ng/mL, P = 0.001), and significantly higher IMT values
      (1.07 +/- 0.4 mm vs. 0.61 +/- 0.1 mm, P < 0.001). A positive correlation was
      observed between IMT and PASI (r = 0.78, P < 0.001), serum psoriasin (r = 0.48, P
      > 0.01) and serum koebnerisin (r = 0.48, P < 0.01). Patients with psoriasis with
      subclinical atherosclerosis had higher serum levels of koebnerisin compared with
      patients without subclinical atherosclerosis (P = 0.04), which was not observed
      for psoriasin (P = 0.94). CONCLUSION: Serum psoriasin and koebnerisin correlate
      with IMT, underlining their value as a potential link between psoriasis and
      atherosclerosis. In particular, koebnerisin seems to be a useful marker of
      subclinical atherosclerosis in patients with psoriasis.

PMID- 29333663
TI  - Computed tomographic retrograde positive contrast cystography and computed
      tomographic excretory urography characterization of a urinary bladder
      diverticulum in a dog.
AB  - A one-year-old intact male German shepherd dog was referred with a 3-month
      history of dysuria and pollakiuria. Physical examination revealed a large firm
      mass in the caudal abdomen. Findings from survey radiography, negative contrast
      cystography, computed tomographic (CT) retrograde positive contrast cystography,
      and CT excretory urography were consistent with a large urinary bladder
      diverticulum. An exploratory laparotomy revealed a normal wall appearance in the
      ventral compartment (true bladder) and marked thinning of the wall in the dorsal
      compartment (diverticulum). Both ureters inserted into the ventral compartment.
      The dorsal compartment was excised and histopathology confirmed the diagnosis of
      urinary bladder diverticulum.

PMID- 29333664
TI  - Increased non-fatal overdose risk associated with involuntary drug treatment in a
      longitudinal study with people who inject drugs.
AB  - AIM: To assess the effect of involuntary drug treatment (IDT) on non-fatal
      overdose among people who inject drugs (PWID). DESIGN: Longitudinal study.
      SETTING: Tijuana, Mexico. PARTICIPANTS: Baseline sample of 671 PWID included 258
      (38.4%) women and 413 (61.6%) men. MEASUREMENTS: Primary independent variables
      were reported recent (i.e. past 6 months) non-fatal overdose event (dependent
      variable) and IDT. Substance use the day of the non-fatal overdose was also
      examined. FINDINGS: From 2011 to 2017, 213 participants (31.7%) reported a recent
      non-fatal overdose and 103 (15.4%) reported recent IDT. Heroin, in combination
      with methamphetamine and tranquilizers, were the drugs most reported at the day
      of the event. IDT significantly increased the odds of reporting a non-fatal
      overdose event [adjusted odds ratio (aOR) = 1.76; 95% confidence interval (CI) =
      1.04-2.96]. Odds of non-fatal overdose also increased independently for each
      additional injection per day (aOR = 1.05; 95% CI = 1.02-1.08), recent
      tranquilizer use (aOR = 1.92; 95% CI = 1.41-2.61) and using hit doctors (aOR =
      1.68; 95% CI = 1.29-2.18) and decreased with age (aOR = 0.97 per year, 95% CI =
      0.95-0.99). CONCLUSIONS: Recent involuntary drug treatment in Mexico is a risk
      factor for non-fatal drug overdose.

PMID- 29333667
TI  - Improved Electron Transport with Reduced Contact Resistance in N-Doped Polymer
      Field-Effect Transistors with a Dimeric Dopant.
AB  - Attaining control on charge injection properties is significant for meaningful
      applications of organic field-effect transistors (OFETs). Here, molecular
      electron-doping is applied with an air-stable dimer dopant for n-type OFETs based
      on (naphthalene diimide-diketopyrrolopyrrole) polymer hosts. Through
      investigating the doping effect on contact and transport properties, it is found
      that the electron transport increases in n-doped OFETs at low doping regime with
      remaining large on/off ratios. These favorable meliorations are reconciled by the
      mitigated impacts of contact resistance and interfacial traps, as well as the
      surface morphology exhibiting features of increased ordering. The occurrence of
      doping in the presence of dimer dopants is evidenced by the observed shift of
      Fermi level toward vacuum level coupled with compositional analysis. Without
      applying vacuum-deposition-based contact doping, charge injection efficiencies
      are gained without losing OFET characteristics using the solution-based
      methodology.

PMID- 29333665
TI  - Clinical and metabolic effects associated with weight changes and obeticholic
      acid in non-alcoholic steatohepatitis.
AB  - BACKGROUND: In a 72-week, randomised controlled trial of obeticholic acid (OCA)
      in non-alcoholic steatohepatitis (NASH), OCA was superior to placebo in improving
      serum ALT levels and liver histology. OCA therapy also reduced weight. AIMS:
      Because weight loss by itself can improve histology, to perform a post hoc
      analysis of the effects of weight loss and OCA treatment in improving clinical
      and metabolic features of NASH. METHODS: The analysis was limited to the 200
      patients with baseline and end-of-treatment liver biopsies. Weight loss was
      defined as a relative decline from baseline of 2% or more at treatment end.
      RESULTS: Weight loss occurred in 44% (45/102) of OCA and 32% (31/98) of placebo
      treated patients (P = 0.08). The NAFLD Activity score (NAS) improved more in
      those with than without weight loss in both the OCA- (-2.4 vs -1.2, P<0.001) and
      placebo-treated patients (-1.2 vs -0.5, P = 0.03). ALT levels also improved in
      those with vs without weight loss in OCA- (-43 vs -34 U/L, P = 0.12) and placebo
      treated patients (-29 vs -10 U/L, P = 0.02). However, among those who lost
      weight, OCA was associated with opposite effects from placebo on changes in
      alkaline phosphatase (+21 vs -12 U/L, P<0.001), total (+13 vs -14 mg/dL, P =
      0.02) and LDL cholesterol (+18 vs -12 mg/dL, P = 0.01), and HbA1c (+0.1 vs -0.4%,
      P = 0.01). CONCLUSIONS: OCA leads to weight loss in up to 44% of patients with
      NASH, and OCA therapy and weight loss have additive benefits on serum
      aminotransferases and histology. However, favourable effects of weight loss on
      alkaline phosphatase, lipids and blood glucose seen in placebo-treated patients
      were absent or reversed on OCA treatment. These findings stress the importance of
      assessing concomitant metabolic effects of new therapies of NASH. Clinical trial
      number: NCT01265498.

PMID- 29333668
TI  - A photonumeric scale for the assessment of atrophic facial photodamage.
AB  - BACKGROUND: Photonumeric scales have consistently shown superiority over
      descriptive equivalents. They have the advantage of providing a consistent visual
      frame of reference by minimizing variability in perception and subjectivity. A
      photonumeric scale to assess hypertrophic facial photodamage already exists.
      However, there is currently no objective measure for atrophic facial photodamage.
      To address this, we have devised a nine-point photonumeric standardized scale.
      OBJECTIVES: To design, test and validate a photonumeric scale for the assessment
      of atrophic facial photodamage against a descriptive scale for the same
      indication. METHODS: A pool of 393 facial photographs (en face and 45 degrees 
      oblique) from 131 individuals with atrophic facial photodamage was created. Five
      photographic standards were selected and assigned grades zero through to eight,
      where zero is no photodamage and eight is severe atrophic photodamage, thus
      making a nine-point scale. Twenty photographs spanning the entire range of values
      were selected to test the scale. Testing was performed alongside a descriptive
      equivalent. A panel of 10 dermatologists, 10 nondermatology clinicians and 14
      dermatology scientists marked the two scales; marking was repeated 1 week later.
      RESULTS: There was a significantly greater agreement between the graders using
      the photonumeric scale than the descriptive scale (kappa values 0.71 and 0.37
      with standardized errors of 0.57 and 0.17, respectively) with no significant
      difference in repeatability between the two methods (P < 0.05). CONCLUSIONS: The
      study describes a new photonumeric scale for atrophic photodamage. This would be
      a useful adjunct in both the clinical and research settings.

PMID- 29333666
TI  - Stable High-Index Faceted Pt Skin on Zigzag-Like PtFe Nanowires Enhances Oxygen
      Reduction Catalysis.
AB  - Selectively exposing active surfaces and judiciously tuning the near-surface
      composition of electrode materials represent two prominent means of promoting
      electrocatalytic performance. Here, a new class of Pt3 Fe zigzag-like nanowires
      (Pt-skin Pt3 Fe z-NWs) with stable high-index facets (HIFs) and nanosegregated Pt
      skin structure is reported, which are capable of substantially boosting
      electrocatalysis in fuel cells. These unique structural features endow the Pt
      skin Pt3 Fe z-NWs with a mass activity of 2.11 A mg-1 and a specifc activity of
      4.34 mA cm-2 for the oxygen reduction reaction (ORR) at 0.9 V versus reversible
      hydrogen electrode, which are the highest in all reported PtFe-based ORR
      catalysts. Density function theory calculations reveal a combination of exposed
      HIFs and formation of Pt-skin structure, leading to an optimal oxygen adsorption
      energy due to the ligand and strain effects, which is responsible for the much
      enhanced ORR activities. In contrast to previously reported HIFs-based catalysts,
      the Pt-skin Pt3 Fe z-NWs maintain ultrahigh durability with little activity decay
      and negligible structure transformation after 50 000 potential cycles. Overcoming
      a key technical barrier in electrocatalysis, this work successfully extends the
      nanosegregated Pt-skin structure to nanocatalysts with HIFs, heralding the
      exciting prospects of high-effcient Pt-based catalysts in fuel cells.

PMID- 29333669
TI  - Blood pressure and goal titration of neurohormonal antagonists: the tortoise wins
      again?

PMID- 29333670
TI  - Pustular psoriasis and related pustular skin diseases.
AB  - Patients with pustular psoriasis or related pustular diseases may have genetic
      abnormalities impairing the function of key players of the innate skin immune
      system. Recently, identification of these abnormalities has changed the paradigm
      of several of these diseases. These include generalized pustular psoriasis,
      palmoplantar pustular psoriasis and acrodermatitis continua of Hallopeau, and
      also drug-induced acute exanthematous generalized pustular eruption. Identified
      mutations in IL36RN, CARD14 and AP1S3 in different groups of patients lead to
      enhanced inflammatory cascade in several cellular subtypes including
      keratinocytes, and to the recruitment and activation of neutrophils and
      macrophages. These insights have unveiled pathophysiological features that shift
      the existing paradigms and emphasize the autoinflammatory nature of skin pustular
      disorders. They also highlight the crucial role of the innate immune system
      across entities belonging to the psoriasis disease spectrum, allowing
      identification of new appealing therapeutic targets.

PMID- 29333671
TI  - Selective enrichment of N-linked glycopeptides and glycans by using a dextran
      modified hydrophilic material.
AB  - Glycosylation analysis of proteins from biological sources utilizing mass
      spectrometry based approaches is challenging due to the relatively low abundance
      of glycopeptides, the structural diversity of glycans, and the coexisting
      matrices. In this study, a customized dextran-bonded silica-based stationary
      phase was introduced for selective enrichment of glycopeptides and glycans from
      complex biological samples. This material has exhibited superior selectivity and
      broader glycosylation site coverage over commercial Sepharose in glycoproteomic
      evaluation. Additionally, the glycomic analysis of fetuin, alpha1 -acid
      glycoprotein, and human serum N-glycome also indicated the relatively higher
      sensitivity, selectivity, and glycoform coverage of dextran-bonded silica than
      that of Sepharose and porous graphitized carbon. Therefore, the dextran-bonded
      silica is expected to make contributions in the fields of glycoproteomics and
      glycomics.

PMID- 29333672
TI  - Controlled pattern imputation for sensitivity analysis of longitudinal binary and
      ordinal outcomes with nonignorable dropout.
AB  - The controlled imputation method refers to a class of pattern mixture models that
      have been commonly used as sensitivity analyses of longitudinal clinical trials
      with nonignorable dropout in recent years. These pattern mixture models assume
      that participants in the experimental arm after dropout have similar response
      profiles to the control participants or have worse outcomes than otherwise
      similar participants who remain on the experimental treatment. In spite of its
      popularity, the controlled imputation has not been formally developed for
      longitudinal binary and ordinal outcomes partially due to the lack of a natural
      multivariate distribution for such endpoints. In this paper, we propose 2
      approaches for implementing the controlled imputation for binary and ordinal data
      based respectively on the sequential logistic regression and the multivariate
      probit model. Efficient Markov chain Monte Carlo algorithms are developed for
      missing data imputation by using the monotone data augmentation technique for the
      sequential logistic regression and a parameter-expanded monotone data
      augmentation scheme for the multivariate probit model. We assess the performance
      of the proposed procedures by simulation and the analysis of a schizophrenia
      clinical trial and compare them with the fully conditional specification, last
      observation carried forward, and baseline observation carried forward imputation
      methods.

PMID- 29333673
TI  - Predicting heart failure: one size does not fit all.

PMID- 29333675
TI  - Sharing innovations to enhance renal fellow education in dialysis.
AB  - Dialysis care is an integral part of the practice of nephrology. Despite this,
      education of fellows in providing dialysis often remains rudimentary, relying on
      a combination of didactics and learning through experience. This runs the risk of
      training nephrologists who can provide dialysis care without truly being experts
      on the subject. In this article, a collection of novel or innovative teaching
      methods is presented that are meant to provide training programs with additional
      tools with which to improve the training of their fellows in dialysis.

PMID- 29333674
TI  - MicroRNA Detection by DNA-Mediated Liposome Fusion.
AB  - Membrane fusion is a process of fundamental importance in biological systems that
      involves highly selective recognition mechanisms for the trafficking of molecular
      and ionic cargos. Mimicking natural membrane fusion mechanisms for the purpose of
      biosensor development holds great potential for amplified detection because
      relatively few highly discriminating targets lead to fusion and an accompanied
      engagement of a large payload of signal-generating molecules. In this work,
      sequence-specific DNA-mediated liposome fusion is used for the highly selective
      detection of microRNA. The detection of miR-29a, a known flu biomarker, is
      demonstrated down to 18 nm within 30 min with high specificity by using a
      standard laboratory microplate reader. Furthermore, one order of magnitude
      improvement in the limit of detection is demonstrated by using a novel imaging
      technique combined with an intensity fluctuation analysis, which is coined two
      color fluorescence correlation microscopy.

PMID- 29333676
TI  - Ether-a-go-go K+ channels: effective modulators of neuronal excitability.
AB  - Mammalian ether-a-go-go (EAG) channels are voltage-gated K+ channels. They are
      encoded by the KCNH gene family and divided into three subfamilies, eag (Kv10),
      erg (eag-related gene; Kv11) and elk (eag-like; Kv12). All EAG channel subtypes
      are expressed in the brain where they effectively modulate neuronal excitability.
      This Topical Review describes the biophysical properties of each of the EAG
      channel subtypes, their function in neurons and the neurological diseases induced
      by EAG channel mutations. In contrast to the function of erg currents in the
      heart, where they contribute to repolarization of the cardiac action potential,
      erg currents in neurons are involved in the maintenance of the resting potential,
      setting of action potential threshold and frequency accommodation. They can even
      support high frequency firing by preventing a depolarization-induced Na+ channel
      block. EAG channels are modulated differentially, e.g. eag channels by
      intracellular Ca2+ , erg channels by extracellular K+ and GPCRs, and elk channels
      by changes in pH. So far, only currents mediated by erg channels have been
      recorded in neurons with the help of selective blockers. Neuronal eag and elk
      currents have not been isolated due to the lack of suitable channel blockers.
      However, findings in KO mice indicate a physiological role of eag1 currents in
      synaptic transmission and an involvement of elk2 currents in cognitive
      performance. Human eag1 and eag2 gain-of-function mutations underlie syndromes
      associated with epileptic seizures.

PMID- 29333679
TI  - Publication ethics-Where are we today? Part 3: The good, the bad, and the ugly
      face of publication.

PMID- 29333678
TI  - Supplementary feeding as a source of multiresistant Salmonella in endangered
      Egyptian vultures.
AB  - Wild birds have repeatedly been highlighted as vectors in the dissemination of
      livestock and human pathogens. Here, the occurrence, serotypes and antimicrobial
      resistance of Salmonella were assessed in adult Egyptian vultures (Neophron
      percnopterus), to test the hypothesis that infection is associated with the
      consumption of swine carcasses provided at supplementary feeding stations (SFSs).
      Faeces of year-round resident griffon vultures (Gyps fulvus) were also tested to
      assess whether infection was acquired in the breeding grounds of both species or
      in the African wintering quarters of Egyptian vultures. Depending on the shedding
      rate criteria considered, the occurrence of infection in Egyptian vultures varied
      between the three consecutive sampling days in a range with a minimum of 23%-41%
      and a maximum of 64%-92% of individuals (n = 11-14 individuals, 27-39 faeces).
      The occurrence in the single sampling of griffon vultures was 61% of faeces (n =
      18). Vultures mostly fed on pig carcasses, which together with their predominant
      infection with multiresistant serotypes (mostly the monophasic 4,12:i:- variant
      resistant to aminopenicillins, aminoglycosides and tetracyclines) typically found
      in pigs from Spain, strongly supports a carcass-to-vulture transmission and cross
      infection routes at SFSs. Efforts are encouraged to avoid discarding carcasses of
      pigs with Salmonella at SFSs established for the conservation of threatened
      scavengers. This could contribute to reducing the long-distance transmission of
      resistant pathogens with an impact on livestock and human health while avoiding
      infection risk and its effects on wildlife.

PMID- 29333677
TI  - Diminished alternative reinforcement as a mechanism linking conduct problems and
      substance use in adolescence: a longitudinal examination.
AB  - AIMS: To determine whether diminished alternative reinforcement (i.e. engagement
      and enjoyment from substance-free activities) mediated the longitudinal
      association of conduct problems with substance use in early-mid-adolescence.
      DESIGN: Structural equation modeling tested whether the association between wave
      1 (baseline) conduct problems and wave 3 (24-month follow-up) substance use
      outcomes was mediated by diminished alternative reinforcement at wave 2 (12-month
      follow-up). Additional analyses tested whether sex and socio-economic status
      moderated this association. SETTING: Ten high schools in Los Angeles, CA, USA,
      2013-15. PARTICIPANTS: Students (n = 3396, 53.5% female, mean [standard deviation
      (SD)] age at wave 1 baseline = 14.1 (0.42) years). MEASUREMENTS: Self-reported
      conduct problems (11-item questionnaire), alternative reinforcement (44-item
      questionnaire) and use of alcohol, marijuana and combustible cigarettes during
      the past 6 months (yes/no) and the past 30 days (nine-level ordinal response
      based on days used in past 30 days). RESULTS: Significant associations of wave 1
      conduct problems with wave 3 marijuana use during the past 6 months (beta = 0.25)
      and past 30 days (beta = 0.26) were mediated by wave 2 diminished alternative
      reinforcement (betaindirect effect : 6 months = 0.013, 30 days = 0.017, Ps <
      0.001). Associations of conduct problems with alcohol or combustible cigarette
      use were not mediated by alternative reinforcement. All associations did not
      differ by sex and socio-economic status. CONCLUSIONS: Diminished alternative
      reinforcement may be a modifiable mechanism linking early adolescent conduct
      problems and subsequent marijuana use that could be targeted in prevention
      programs to offset the adverse health and social sequelae associated with
      comorbid conduct problems and marijuana use in early-mid adolescence.

PMID- 29333680
TI  - Cellulose-Based Biomimetics and Their Applications.
AB  - Nature has been producing cellulose since long before man walked the surface of
      the earth. Millions of years of natural design and testing have resulted in
      cellulose-based structures that are an inspiration for the production of
      synthetic materials based on cellulose with properties that can mimic natural
      designs, functions, and properties. Here, five sections describe cellulose-based
      materials with characteristics that are inspired by gratings that exist on the
      petals of the plants, structurally colored materials, helical filaments produced
      by plants, water-responsive materials in plants, and environmental stimuli
      responsive tissues found in insects and plants. The synthetic cellulose-based
      materials described herein are in the form of fibers and films. Fascinating
      multifunctional materials are prepared from cellulose-based liquid crystals and
      from composite cellulosic materials that combine functionality with structural
      performance. Future and recent applications are outlined.

PMID- 29333681
TI  - Myotropic activity and immunolocalization of selected neuropeptides of the
      burying beetle Nicrophorus vespilloides (Coleoptera: Silphidae).
AB  - Burying beetles (Nicrophorus sp.) are necrophagous insects with developed
      parental care. Genome of Nicrophorus vespilloides has been recently sequenced,
      which makes them interesting model organism in behavioral ecology. However, we
      know very little about their physiology, including the functioning of their
      neuroendocrine system. In this study, one of the physiological activities of
      proctolin, myosuppressin (Nicve-MS), myoinhibitory peptide (Trica-MIP-5) and the
      short neuropeptide F (Nicve-sNPF) in N. vespilloides have been investigated. The
      tested neuropeptides were myoactive on N. vespilloides hindgut. After application
      of the proctolin increased hindgut contraction frequency was observed (EC50 value
      was 5.47 * 10-8 mol/L). The other tested neuropeptides led to inhibition of N.
      vespilloides hindgut contractions (Nicve-MS: IC50 = 5.20 * 10-5 mol/L; Trica-MIP
      5: IC50 = 5.95 * 10-6 mol/L; Nicve-sNPF: IC50 = 4.08 * 10-5 mol/L). Moreover, the
      tested neuropeptides were immunolocalized in the nervous system of N.
      vespilloides. Neurons containing sNPF and MIP in brain and ventral nerve cord
      (VNC) were identified. Proctolin-immunolabeled neurons only in VNC were observed.
      Moreover, MIP-immunolabeled varicosities and fibers in retrocerebral complex were
      observed. In addition, our results have been supplemented with alignments of
      amino acid sequences of these neuropeptides in beetle species. This alignment
      analysis clearly showed amino acid sequence similarities between neuropeptides.
      Moreover, this allowed to deduce amino acid sequence of N. vespilloides proctolin
      (RYLPTa), Nicve-MS (QDVDHVFLRFa) and six isoforms of Nicve-MIP (Nicve-MIP-1
      DWNRNLHSWa; Nicve-MIP-2-AWQNLQGGWa; Nicve-MIP-3-AWQNLQGGWa; Nicve-MIP-4
      AWKNLNNAGWa; Nicve-MIP-5-SEWGNFRGSWa; Nicve-MIP-6- DPAWTNLKGIWa; and Nicve-sNPF
      SGRSPSLRLRFa).

PMID- 29333682
TI  - Selective extraction of bisphenol A from water by one-monomer molecularly
      imprinted magnetic nanoparticles.
AB  - One-monomer molecularly imprinted magnetic nanoparticles were prepared as
      adsorbents for selective extraction of bisphenol A from water in this study. A
      single bi-functional monomer was adopted for preparation of the molecularly
      imprinted polymer, avoiding the tedious trial-and-error optimizations as
      traditional strategy. Moreover, bisphenol F was used as the dummy template for
      bisphenol A to avoid the interference from residual template molecules. These
      nanoparticles showed not only large adsorption capacity and good selectivity to
      the bisphenol A but also outstanding magnetic response performance. Furthermore,
      they were successfully used as magnetic solid-phase extraction adsorbents of
      bisphenol A from various water samples, including tap water, river water, and
      seawater. The developed method was found to be much more efficient, convenient,
      and economical for selective extraction of bisphenol A compared with the
      traditional solid-phase extraction. Separation of these nanoparticles can be
      easily achieved with an external magnetic field, and the optimized adsorption
      time was only 15 min. The recoveries of bisphenol A in different water samples
      ranged from 85.38 to 93.75%, with relative standard deviation lower than 7.47%.
      These results showed that one-monomer molecularly imprinted magnetic
      nanoparticles had the potential to be popular adsorbents for selective extraction
      of pollutants from water.

PMID- 29333683
TI  - Mobility Engineering in Vertical Field Effect Transistors Based on Van der Waals
      Heterostructures.
AB  - Vertical integration of 2D layered materials to form van der Waals
      heterostructures (vdWHs) offers new functional electronic and optoelectronic
      devices. However, the mobility in vertical carrier transport in vdWHs of vertical
      field-effect transistor (VFET) is not yet investigated in spite of the importance
      of mobility for the successful application of VFETs in integrated circuits. Here,
      the mobility in VFET of vdWHs under different drain biases, gate biases, and
      metal work functions is first investigated and engineered. The traps in WSe2 are
      the main source of scattering, which influences the vertical mobility and three
      distinct transport mechanisms: Ohmic transport, trap-limited transport, and space
      charge-limited transport. The vertical mobility in VFET can be improved by
      suppressing the trap states by raising the Fermi level of WSe2 . This is achieved
      by increasing the injected carrier density by applying a high drain voltage, or
      decreasing the Schottky barrier at the graphene/WSe2 and metal/WSe2 junctions by
      applying a gate bias and reducing the metal work function, respectively.
      Consequently, the mobility in Mn vdWH at +50 V gate voltage is about 76 times
      higher than the initial mobility of Au vdWH. This work enables further
      improvements in the VFET for successful application in integrated circuits.

PMID- 29333684
TI  - Biocatalytic Synthesis of Nitriles through Dehydration of Aldoximes: The
      Substrate Scope of Aldoxime Dehydratases.
AB  - Nitriles, which are mostly needed and produced by the chemical industry, play a
      major role in various industry segments, ranging from high-volume, low-price
      sectors, such as polymers, to low-volume, high-price sectors, such as chiral
      pharma drugs. A common industrial technology for nitrile production is
      ammoxidation as a gas-phase reaction at high temperature. Further popular
      approaches are substitution or addition reactions with hydrogen cyanide or
      derivatives thereof. A major drawback, however, is the very high toxicity of
      cyanide. Recently, as a synthetic alternative, a novel enzymatic approach towards
      nitriles has been developed with aldoxime dehydratases, which are capable of
      converting an aldoxime in one step through dehydration into nitriles. Because the
      aldoxime substrates are easily accessible, this route is of high interest for
      synthetic purposes. However, whenever a novel method is developed for organic
      synthesis, it raises the question of substrate scope as one of the key criteria
      for application as a "synthetic platform technology". Thus, the scope of this
      review is to give an overview of the current state of the substrate scope of this
      enzymatic method for synthesizing nitriles with aldoxime dehydratases. As a
      recently emerging enzyme class, a range of substrates has already been studied so
      far, comprising nonchiral and chiral aldoximes. This enzyme class of aldoxime
      dehydratases shows a broad substrate tolerance and accepts aliphatic and aromatic
      aldoximes, as well as arylaliphatic aldoximes. Furthermore, aldoximes with a
      stereogenic center are also recognized and high enantioselectivities are found
      for 2-arylpropylaldoximes, in particular. It is further noteworthy that the
      enantiopreference depends on the E and Z isomers. Thus, opposite enantiomers are
      accessible from the same racemic aldehyde and the same enzyme.

PMID- 29333685
TI  - Co(OH)2 Nanoparticle-Encapsulating Conductive Nanowires Array: Room-Temperature
      Electrochemical Preparation for High-Performance Water Oxidation
      Electrocatalysis.
AB  - It is highly desired but still remains challenging to design and develop a Co
      based nanoparticle-encapsulated conductive nanoarray at room temperature for high
      performance water oxidation electrocatalysis. Here, it is reported that room
      temperature anodization of a Co(TCNQ)2 (TCNQ = tetracyanoquinodimethane) nanowire
      array on copper foam at alkaline pH leads to in situ electrochemcial oxidation of
      TCNQ- into water-insoluable TCNQ nanoarray embedding Co(OH)2 nanoparticles. Such
      Co(OH)2 -TCNQ/CF shows superior catalytic activity for water oxidation and
      demands only a low overpotential of 276 mV to drive a geometrical current density
      of 25 mA cm-2 in 1.0 m KOH. Notably, it also demonstrates strong long-term
      electrochemical durability with its activity being retrained for at least 25 h, a
      high turnover frequency of 0.97 s-1 at an overpotential of 450 mV and 100%
      Faradic efficiency. This study provides an exciting new method for the rational
      design and development of a conductive TCNQ-based nanoarray as an interesting 3D
      material for advanced electrochemical applications.

PMID- 29333686
TI  - Predicting hypertension among Korean cancer survivors: A nationwide population
      based study.
AB  - Hypertension is the most common comorbidity among cancer survivors, although
      there is no model for predicting hypertension in this population. Therefore, we
      developed a model for predicting hypertension using data from 6,480 Korean cancer
      survivors who were >=20 years old. The odds ratios (ORs) for hypertension were
      calculated using stepwise logistic regression analyses, and a nomogram was
      generated to predict hypertension. Hypertension was independently associated with
      an age of >=65 years (OR: 3.058), male gender (OR: 1.195), obesity (OR: 1.998),
      prehypertension (OR: 2.06), dyslipidaemia (OR: 2.011) and diabetes mellitus (OR:
      2.297). Each variable in the nomogram was assigned a specific number of points,
      and the total score (range: 0-400) was used to obtain a value for predicting
      hypertension. The estimated prevalence of hypertension increased when the total
      nomogram score exceeded the sixth decile (total points: 128; p for trend <.001).
      Therefore, among Korean cancer survivors, hypertension was significantly
      associated with an age of >65 years, male gender, obesity, and having various
      comorbidities (e.g., prehypertension, dyslipidaemia and diabetes mellitus).
      Furthermore, our nomogram could predict the incidence of hypertension, and the
      sixth decile of the total nomogram score predicted an increased risk of
      hypertension.

PMID- 29333687
TI  - H9N2 influenza virus isolated from minks has enhanced virulence in mice.
AB  - H9N2 is one of the major subtypes of influenza virus circulating in poultry in
      China, which has a wide host range from bird to mammals. Two H9N2 viruses were
      isolated from one mink farm in 2014. Phylogenetic analysis showed that internal
      genes of the H9N2 viruses have close relationship with those of H7N9 viruses.
      Interestingly, two H9N2 were separated in phylogenetic trees, indicating that
      they are introduced to this mink farm in two independent events. And further mice
      studies showed that one H9N2 caused obvious weight loss and 20% mortality in
      infected mice, while another virus did not cause any clinical sign in mice
      infected at the same dose. Genetic analysis indicated that the virulent H9N2
      contain a natural mutation at 701N in PB2 protein, which was reported to
      contribute to mammalian adaptation. However, such substitution is absent in the
      H9N2 avirulent to mice. Circulation of H9N2 in mink may drive the virus to adapt
      mammals; continual surveillance of influenza virus in mink was warranted.

PMID- 29333689
TI  - 2D-Black-Phosphorus-Reinforced 3D-Printed Scaffolds:A Stepwise Countermeasure for
      Osteosarcoma.
AB  - With the ever-deeper understanding of nano-bio interactions and the development
      of fabrication methodologies of nanomaterials, various therapeutic platforms
      based on nanomaterials have been developed for next-generation oncological
      applications, such as osteosarcoma therapy. In this work, a black phosphorus (BP)
      reinforced 3D-printed scaffold is designed and prepared to provide a feasible
      countermeasure for the efficient localized treatment of osteosarcoma. The in situ
      phosphorus-driven, calcium-extracted biomineralization of the intra-scaffold BP
      nanosheets enables both photothermal ablation of osteosarcoma and the subsequent
      material-guided bone regeneration in physiological microenvironment, and in the
      meantime endows the scaffolds with unique physicochemical properties favoring the
      whole stepwise therapeutic process. Additionally, a corrugated structure
      analogous to Haversian canals is found on newborn cranial bone tissue of Sprague
      Dawley rats, which may provide much inspiration for the future research of bone
      tissue engineering.

PMID- 29333688
TI  - Infant brain responses to felt and observed touch of hands and feet: an MEG
      study.
AB  - There is growing interest concerning the ways in which the human body, both one's
      own and that of others, is represented in the developing human brain. In two
      experiments with 7-month-old infants, we employed advances in infant
      magnetoencephalography (MEG) brain imaging to address novel questions concerning
      body representations in early development. Experiment 1 evaluated the
      spatiotemporal organization of infants' brain responses to being touched. A
      punctate touch to infants' hands and feet produced significant activation in the
      hand and foot areas of contralateral primary somatosensory cortex as well as in
      other parietal and frontal areas. Experiment 2 explored infant brain responses to
      visually perceiving another person's hand or foot being touched. Results showed
      significant activation in early visual regions and also in regions thought to be
      involved in multisensory body and self-other processing. Furthermore, observed
      touch of the hand and foot activated the infant's own primary somatosensory
      cortex, although less consistently than felt touch. These findings shed light on
      aspects of early social cognition, including action imitation, which may build,
      at least in part, on infant neural representations that map equivalences between
      the bodies of self and other.

PMID- 29333690
TI  - High-Capacity Cathode Material with High Voltage for Li-Ion Batteries.
AB  - Electrochemical energy storage devices with a high energy density are an
      important technology in modern society, especially for electric vehicles. The
      most effective approach to improve the energy density of batteries is to search
      for high-capacity electrode materials. According to the concept of energy
      quality, a high-voltage battery delivers a highly useful energy, thus providing a
      new insight to improve energy density. Based on this concept, a novel and
      successful strategy to increase the energy density and energy quality by
      increasing the discharge voltage of cathode materials and preserving high
      capacity is proposed. The proposal is realized in high-capacity Li-rich cathode
      materials. The average discharge voltage is increased from 3.5 to 3.8 V by
      increasing the nickel content and applying a simple after-treatment, and the
      specific energy is improved from 912 to 1033 Wh kg-1 . The current work provides
      an insightful universal principle for developing, designing, and screening
      electrode materials for high energy density and energy quality.

PMID- 29333692
TI  - Measuring spatial and temporal trends of nicotine and alcohol consumption in
      Australia using wastewater-based epidemiology.
AB  - BACKGROUND AND AIMS: Tobacco and alcohol consumption remain priority public
      health issues world-wide. As participation in population-based surveys has
      fallen, it is increasingly challenging to estimate accurately the prevalence of
      alcohol and tobacco use. Wastewater-based epidemiology (WBE) is an alternative
      approach for estimating substance use at the population level that does not rely
      upon survey participation. This study examined spatio-temporal patterns in
      nicotine (a proxy for tobacco) and alcohol consumption in the Australian
      population via WBE. METHODS: Daily wastewater samples (n = 164) were collected at
      18 selected wastewater treatment plants across Australia, covering approximately
      45% of the total population. Nicotine and alcohol metabolites in the samples were
      measured using liquid chromatography-tandem mass spectrometry. Daily consumption
      of nicotine and alcohol and its associated uncertainty were computed using Monte
      Carlo simulations. Nation-wide daily average and weekly consumption of these two
      substances were extrapolated using ordinary least squares and mixed-effect
      models. FINDINGS: Nicotine and alcohol consumption was observed in all
      communities. Consumption of these substances in rural towns was three to four
      times higher than in urban communities. The spatial consumption pattern of these
      substances was consistent across the monitoring periods in 2014-15. Nicotine
      metabolites significantly reduced by 14-25% (P = 0.001-0.008) (2014-15) in some
      catchments. Alcohol consumption remained constant over the studied periods.
      Strong weekly consumption patterns were observed for alcohol but not nicotine.
      Nation-wide, the daily average consumption per person (aged 15-79 years) was
      estimated at approximately 2.5 cigarettes and 1.3-2.0 standard drinks (weekday
      weekend) of alcohol. These estimates were close to the sale figure and apparent
      consumption, respectively. CONCLUSIONS: Wastewater-based epidemiology is a
      feasible method for objectively evaluating the geographic, temporal and weekly
      profiles of nicotine and alcohol consumption in different communities nationally.

PMID- 29333693
TI  - Polypeptide Polymer Brushes by Light-Induced Surface Polymerization of Amino Acid
      N-Carboxyanhydrides.
AB  - Silicon wafers are decorated with photoamine generator 4,5-dimethoxy-2
      nitrobenzyl 3-(triethoxysilyl)propyl carbamate. UV-irradiation in the presence of
      benzyl-l-glutamate N-carboxyanhydride is carried out, resulting in the release of
      the surface-bound primary amines, making them viable N-carboxyanhydride (NCA)
      polymerization initiators. Successful polypeptide grafting is confirmed by water
      contact angle measurements as well as by ellipsometry, revealing a poly(benzyl-l
      glutamate) (PBLG) layer of ~3 nm. X-ray photoelectron spectroscopy confirms the
      presence of amide groups in the grafted PBLG while time-of-flight secondary ion
      mass spectroscopy provides additional evidence for the presence of PBLG on the
      surface. Evaluation of negative control samples confirms successful UV surface
      grafting. The approach is thus established as a viable general method for light
      exposure directable polypeptide functionalization of silicon surfaces.

PMID- 29333695
TI  - FCI Literature Prize: T. Schirmeister, C. Schmuck, P. R. Wich / Foundation for
      Polish Science Award: D. T. Gryko / Heinz Award: J. M. DeSimone.

PMID- 29333694
TI  - Chemical Composition Fractionation of Olefin Plastomers/Elastomers by Solvent and
      Thermal Gradient Interaction Chromatography.
AB  - Olefin plastomers/elastomers are typically copolymers with high comonomer
      contents and low crystallinities. Therefore, the fractionation of these materials
      with crystallization-based methods is not feasible. On the other hand, solvent
      and temperature gradient interaction chromatography (SGIC and TGIC, respectively)
      are suitable techniques for the separation of olefin copolymers with regard to
      their chemical composition. In this study, the application ranges of both
      techniques are investigated and compared for ethylene-propylene (EP) copolymers.
      A linear dependency of ethylene content versus elution volume is obtained with
      SGIC in practically the whole ethylene range. In the case of TGIC, a linear
      dependency is obtained within certain ethylene content limits. The accessible
      ethylene content separation range for TGIC is 50-100 mol% ethylene, and a broader
      26-100 mol% ethylene range is accessible for SGIC, the latter being the technique
      of choice in the analysis of EP rubbers.

PMID- 29333691
TI  - The innate immune system in chronic cardiomyopathy: a European Society of
      Cardiology (ESC) scientific statement from the Working Group on Myocardial
      Function of the ESC.
AB  - Activation of the immune system in heart failure (HF) has been recognized for
      over 20 years. Initially, experimental studies demonstrated a maladaptive role of
      the immune system. However, several phase III trials failed to show beneficial
      effects in HF with therapies directed against an immune activation. Preclinical
      studies today describe positive and negative effects of immune activation in HF.
      These different effects depend on timing and aetiology of HF. Therefore, herein
      we give a detailed review on immune mechanisms and their importance for the
      development of HF with a special focus on commonalities and differences between
      different forms of cardiomyopathies. The role of the immune system in ischaemic,
      hypertensive, diabetic, toxic, viral, genetic, peripartum, and autoimmune
      cardiomyopathy is discussed in depth. Overall, initial damage to the heart leads
      to disease specific activation of the immune system whereas in the chronic phase
      of HF overlapping mechanisms occur in different aetiologies.

PMID- 29333696
TI  - The Plantain Proteome, a Focus on Allele Specific Proteins Obtained from Plantain
      Fruits.
AB  - Proteomics has been applied with great potential to elucidate molecular
      mechanisms in plants. This is especially valid in the case of non-model crops of
      which their genome has not been sequenced yet, or is not well annotated.
      Plantains are a kind of cooking bananas that are economically very important in
      Africa, India, and Latin America. The aim of this work was to characterize the
      fruit proteome of common dessert bananas and plantains and to identify proteins
      that are only encoded by the plantain genome. We present the first plantain fruit
      proteome. All data are available via ProteomeXchange with identifier PXD005589.
      Using our in-house workflow, we found 37 alleles to be unique for plantain
      covered by 59 peptides. Although we do not have access (yet) to whole-genome
      sequencing data from triploid banana cultivars, we show that proteomics is an
      easily accessible complementary alternative to detect different allele specific
      SNPs/SAAPs. These unique alleles might contribute toward the differences in the
      metabolism between dessert bananas and plantains. This dataset will stimulate
      further analysis by the scientific community, boost plantain research, and
      facilitate plantain breeding.

PMID- 29333697
TI  - Lactic Acid Bacteria May Impact Intestinal Barrier Function by Modulating Goblet
      Cells.
AB  - SCOPE: Lactic acid bacteria (LAB) are recognized to promote gastrointestinal
      health by mechanisms that are not fully understood. LABs might modulate the mucus
      and thereby enhance intestinal barrier function. Herein, we investigate effects
      of different LAB strains and species on goblet cell genes involved in mucus
      synthesis. METHODS AND RESULTS: Gene expression profiles of goblet-cell
      associated products (mucin MUC2, trefoil factor 3, resistin-like molecule beta,
      carbohydrate sulfotransferase 5, and galactose-3-O-sulfotransferase 2) induced by
      LAB or their derived conditioned medium in human goblet cell line LS174T are
      studied. Effects of LAB on gene transcription are assessed with or without
      exposure to TNF-alpha, IL-13, or the mucus damaging agent tunicamycin. LAB do
      impact the related genes in a species- and strain-specific fashion and their
      effects are different in the presence of the cytokines and tunicamycin. Bioactive
      factors secreted by some strains are also found to regulate goblet cell-related
      genes. CONCLUSION: Our findings provide novel insights in differences in
      modulatory efficacy on mucus genes between LAB species and strains. This study
      further unravels direct interactions between LAB and intestinal goblet cells, and
      highlights the importance of rationally selecting appropriate LAB candidates to
      achieve specific benefits in the gut.

PMID- 29333698
TI  - Design of Enzyme Micelles with Controllable Concavo-Convex Micromorphologies for
      Highly Enhanced Stability and Catalytical Activity.
AB  - Concavo-convex micelles with controllable sizes and nanostructures are prepared
      via self-assembling polymer-enzyme (e.g., shellac enzyme) conjugates with
      heterogeneous polymer chains, which exhibit higher enzyme stability (300%) and
      bioactivity (760%) comparing with the well-defined ones. The applied amphiphilic
      and negatively charged copolymer, poly (methyl methacrylate)-block-poly (sodium p
      styrene sulfonate), is synthesized via reversible addition-fragmentation chain
      transfer polymerization to modify shellac enzyme and immobilize the enzyme
      bioactivity inducer by covalent conjugation and electrostatic attraction,
      respectively. The degradation test of catechol confirms the application potential
      of as-prepared micelles as an efficient and economical decontaminant.

PMID- 29333699
TI  - Pomegranate-Structured Silica/Sulfur Composite Cathodes for High-Performance
      Lithium-Sulfur Batteries.
AB  - Porous materials have many structural advantages for energy storage and
      conversion devices such as rechargeable batteries, supercapacitors, and fuel
      cells. When applied as a host material in lithium-sulfur batteries, porous silica
      materials with a pomegranate-like architecture can not only act as a buffer
      matrix for accommodating a large volume change of sulfur, but also suppress the
      polysulfide shuttle effect. The porous silica/sulfur composite cathodes exhibit
      excellent electrochemical performances including a high specific capacity of 1450
      mA h g-1 , a reversible capacity of 82.9 % after 100 cycles at a rate of C/2 (1
      C=1672 mA g-1 ) and an extended cyclability over 300 cycles at 1 C-rate.
      Furthermore, the high polysulfide adsorption property of porous silica has been
      proven by ex-situ analyses, showing a relationship between the surface area of
      silica and polysulfide adsorption ability. In particular, the modified porous
      silica/sulfur composite cathode, which is treated by a deep-lithiation process in
      the first discharge step, exhibits a highly reversible capacity of 94.5 % at 1C
      rate after 300 cycles owing to a formation of lithiated-silica frames and stable
      solid-electrolyte-interphase layers.

PMID- 29333700
TI  - Understanding Australian medical student attitudes towards older people.
AB  - OBJECTIVE: The aim of this article was to review the literature around Australian
      medical student attitudes towards older people. METHODS: An Ovid cross-search and
      SCOPUS search were performed using keywords such as 'Attitude', 'Medical Student'
      and 'Aged or Older or Elderly'. RESULTS: Several recent studies have investigated
      the attitudes of Australian medical students towards older people. Baseline
      attitudes at two medical schools were positive. Three studies quantified attitude
      improvement after curriculum intervention. All the studies used US-developed
      instruments, which have not been validated in Australia. Qualitative studies have
      described mixed attitudes towards older people: negative themes included
      nihilism, paternalism, communication issues, greater morbidity and reduced
      quality of life. Positively, students placed value on clinical decision-making
      and critical reflection during residential aged care placements. CONCLUSION:
      Australian medical students' attitudes towards older people are mixed and not
      well understood based on quantitative measures developed for use in the US and on
      qualitative evidence. Future research in this area requires a reliable and
      locally-validated instrument.

PMID- 29333701
TI  - The Childhood Arthritis and Rheumatology Research Alliance Consensus Treatment
      Plans: Toward Comparative Effectiveness in the Pediatric Rheumatic Diseases.
AB  - The pediatric rheumatic diseases are a heterogeneous group of rare diseases,
      posing a number of challenges for the use of traditional clinical and
      translational research methods. Innovative comparative effectiveness approaches
      are needed to efficiently study treatment strategies and disease outcomes. The
      Childhood Arthritis and Rheumatology Research Alliance (CARRA) developed the
      consensus treatment plan (CTP) approach as a comparative effectiveness tool for
      research in pediatric rheumatology. CTPs are treatment strategies, developed by
      consensus methods among CARRA members, intended to reduce variation in treatment
      approaches, standardize outcome measurements, and allow for comparison of the
      effectiveness of different approaches with the goal of improving disease
      outcomes. To date, CTPs have been published for 8 different diseases and disease
      manifestations. The approach has been successfully piloted for juvenile localized
      scleroderma, systemic juvenile idiopathic arthritis (JIA), polyarticular JIA,
      dermatomyositis, and lupus nephritis. Large-scale studies are underway for
      systemic JIA and polyarticular JIA, with the CARRA patient registry serving as
      the data collection platform. These studies have been designed with stakeholder
      involvement, including active input from CARRA providers, patients, and parents,
      with the goal of increasing feasibility and ensuring the relevance of the
      outcomes. These studies include ancillary biologic specimen collection intended
      to support additional translational and mechanistic studies. Data from these
      ongoing CTP studies will provide more information on the ability of this approach
      to identify effective treatment strategies and improve outcomes in the pediatric
      rheumatic diseases.

PMID- 29333702
TI  - MAML1 and TWIST1 co-overexpression promote invasion of head and neck squamous
      cell carcinoma.
AB  - AIMS: Head and neck squamous cell carcinoma (HNSCC) is the seventh most common
      cancer worldwide with considerable morbidity and mortality. Invasion and
      metastasis of HNSCC is a complex process involving multiple molecules and
      signaling pathways. Twist Family BHLH Transcription Factor 1 (TWIST1) and
      Mastermind-like 1 (MAML1) are essential in induction of epithelial-mesenchymal
      transition through direct regulation of implicated molecules in cellular
      adhesion, migration and invasion. Our aim in this study was to assess the
      clinical significance of MAML1 and TWIST1 expression in HNSCC, and elucidate the
      probable correlation between these genes to exhibit their possible associations
      with progression and metastasis of the disease. METHODS: The gene expression
      profile of MAML1 and TWIST1 was assessed in fresh tumoral compared to distant
      tumor-free tissues of 55 HNSCC patients using quantitative real-time Polymerase
      chain reaction (PCR). RESULTS: Significant overexpression of MAML1 and TWIST1
      mRNA was observed in 49.1% and 38.2% (P ? 0.05) of tumor specimens, respectively.
      Overexpression of MAML1 was associated with vascular invasion (P = 0.048).
      Concomitant overexpression of MAML1 and TWIST1 was significantly correlated to
      each other (P = 0.004). Co-overexpression of the genes was significantly
      correlated to the various clinicopathological indices of poor prognosis including
      depth of tumor invasion (P < 0.01), lymphatic invasion and grade of tumor cell
      differentiation (P < 0.05). CONCLUSIONS: Significant correlation between MAML1
      and TWIST1 in HNSCC was revealed. This study was the first report elucidating
      MAML1 clinical relevance in HNSCC. These new findings suggest an oncogenic role
      for concomitant expression of MAML1 and TWIST1 genes in HNSCC invasion and
      metastasis.

PMID- 29333703
TI  - Clinical aspects of diabetes in pregnancy.

PMID- 29333704
TI  - Asian horses deepen the MSY phylogeny.
AB  - Humans have shaped the population history of the horse ever since domestication
      about 5500 years ago. Comparative analyses of the Y chromosome can illuminate the
      paternal origin of modern horse breeds. This may also reveal different breeding
      strategies that led to the formation of extant breeds. Recently, a horse Y
      chromosomal phylogeny of modern horses based on 1.46 Mb of the male-specific Y
      (MSY) was generated. We extended this dataset with 52 samples from five European,
      two American and seven Asian breeds. As in the previous study, almost all modern
      European horses fall into a crown group, connected via a few autochthonous
      Northern European lineages to the outgroup, the Przewalski's Horse. In total, we
      now distinguish 42 MSY haplotypes determined by 158 variants within domestic
      horses. Asian horses show much higher diversity than previously found in European
      breeds. The Asian breeds also introduce a deep split to the phylogeny,
      preliminarily dated to 5527 +/- 872 years. We conclude that the deep splitting
      Asian Y haplotypes are remnants of a far more diverse ancient horse population,
      whose haplotypes were lost in other lineages.

PMID- 29333706
TI  - Estimating the footprint of pollution on coral reefs with models of species
      turnover.
AB  - Ecological communities typically change along gradients of human impact, although
      it is difficult to estimate the footprint of impacts for diffuse threats such as
      pollution. We developed a joint model (i.e., one that includes multiple species
      and their interactions with each other and environmental covariates) of benthic
      habitats on lagoonal coral reefs and used it to infer change in benthic
      composition along a gradient of distance from logging operations. The model
      estimated both changes in abundances of benthic groups and their compositional
      turnover, a type of beta diversity. We used the model to predict the footprint of
      turbidity impacts from past and recent logging. Benthic communities far from
      logging were dominated by branching corals, whereas communities close to logging
      had higher cover of dead coral, massive corals, and soft sediment. Recent impacts
      were predicted to be small relative to the extensive impacts of past logging
      because recent logging has occurred far from lagoonal reefs. Our model can be
      used more generally to estimate the footprint of human impacts on ecosystems and
      evaluate the benefits of conservation actions for ecosystems.

PMID- 29333705
TI  - A Light Harvesting, Self-Powered Monolith Tactile Sensor Based on Electric Field
      Induced Effects in MAPbI3 Perovskite.
AB  - Organolead trihalide perovskite MAPbI3 shows a distinctive combination of
      properties such as being ferroelectric and semiconducting, with ion migration
      effects under poling by electric fields. The combination of its ferroelectric and
      semiconducting nature is used to make a light harvesting, self-powered tactile
      sensor. This sensor interfaces ZnO nanosheets as a pressure-sensitive drain on
      the MAPbI3 film and once poled is operational for at least 72 h with just light
      illumination. The sensor is monolithic in structure, has linear response till 76
      kPa, and is able to operate continuously as the energy harvesting mechanism is
      decoupled from its pressure sensing mechanism. It has a sensitivity of 0.57 kPa-1
      , which can be modulated by the strength of the poling field. The understanding
      of these effects in perovskite materials and their application in power source
      free devices are of significance to a wide array of fields where these materials
      are being researched and applied.

PMID- 29333707
TI  - Impact of Gastric Acid Induced Surface Changes on Mechanical Behavior and Optical
      Characteristics of Dental Ceramics.
AB  - PURPOSE: To test the impact of exposure to artificial gastric acid combined with
      toothbrush abrasion on the properties of dental ceramics. Earlier research has
      indicated that immersion in artificial gastric acid has caused increased surface
      roughness of dental ceramics; however, the combined effects of acid immersion and
      toothbrush abrasion and the impact of increased surface roughness on mechanical
      strength and optical properties have not been studied. MATERIALS AND METHODS:
      Three commercially available ceramics were chosen for this study: feldspathic
      porcelain, lithium disilicate glass-ceramic, and monolithic zirconium oxide. The
      specimens (10 * 1 mm discs) were cut, thermally treated as required, and
      polished. Each material was divided into four groups (n = 8 per group): control
      (no exposure), acid only, brush only, acid + brush. The specimens were immersed
      in artificial gastric acid (50 ml of 0.2% [w/v] sodium chloride in 0.7% [v/v]
      hydrochloric acid mixed with 0.16 g of pepsin powder, pH = 2) for 2 minutes and
      rinsed with deionized water for 2 minutes. The procedure was repeated 6 times/day
      * 9 days, and specimens were stored in deionized water at 37 degrees C.
      Toothbrush abrasion was performed using an ISO/ADA design brushing machine for
      100 cycles/day * 9 days. The acid + brush group received both treatments.
      Specimens were examined under SEM and an optical microscope for morphological
      changes. Color and translucency were measured using spectrophotometer CIELAB
      coordinates (L*, a*, b*). Surface gloss was measured using a gloss meter. Surface
      roughness was measured using a stylus profilometer. Biaxial flexural strength was
      measured using a mechanical testing machine. The data were analyzed by one-way
      ANOVA followed by Tukey's HSD post hoc test (p < 0.05). RESULTS: Statistically
      significant changes were found for color, gloss, and surface roughness for
      porcelain and e.max specimens. No statistically significant changes were found
      for any properties of zirconia specimens. CONCLUSIONS: The acid treatment
      affected the surface roughness, color, and gloss of porcelain and e.max ceramics.
      The changes in translucency and mechanical strength for all materials were not
      statistically significant. Zirconia ceramic showed resistance to all treatments.

PMID- 29333709
TI  - The 'airway spider': an education tool to assist teaching human factors and
      ergonomics in airway management.

PMID- 29333708
TI  - Difficult mask ventilation and muscle relaxation.

PMID- 29333710
TI  - Mechanical ventilation mode and postoperative pulmonary complications - a reply.

PMID- 29333711
TI  - Double-blind and single-blind retractable placebo needles.

PMID- 29333712
TI  - Comparing bougie-guided and conventional nasotracheal intubations using
      videolaryngoscopy.

PMID- 29333713
TI  - Difficult mask ventilation and muscle relaxation - a reply.

PMID- 29333714
TI  - Mechanical ventilation mode and postoperative pulmonary complications.

PMID- 29333715
TI  - Social prescribing and pre-operative care.

PMID- 29333716
TI  - National standards for triaging elderly trauma patients.

PMID- 29333717
TI  - Correction.

PMID- 29333718
TI  - Standard abbreviations.

PMID- 29333719
TI  - Ion Mobility-Enhanced Data-Independent Acquisitions Enable a Deep Proteomic
      Landscape of Oligodendrocytes.

PMID- 29333720
TI  - Degree of SGLT1 phosphorylation is associated with but does not determine segment
      specific glucose transport features in the porcine small intestines.
AB  - Glucose-induced electrogenic ion transport is higher in the porcine ileum
      compared with the jejunum despite equal apical abundance of SGLT1. The objective
      of this study was a detailed determination of SGLT1 and GLUT2 expressions at mRNA
      and protein levels along the porcine small intestinal axis. Phosphorylation of
      SGLT1 at serine 418 was assessed as a potential modulator of activity. Porcine
      intestinal tissues taken along the intestinal axis 1 h or 3 h after feeding were
      analyzed for relative mRNA (RT-PCR) and protein levels (immunoblot) of SGLT1,
      pSGLT1, GLUT2, (p)AMPK, beta2 -receptor, and PKA substrates. Functional studies
      on electrogenic glucose transport were done (Ussing chambers: short circuit
      currents (Isc )). Additionally, effects of epinephrine (Epi) administration on
      segment-specific glucose transport and pSGLT1 content were examined. SGLT1 and
      GLUT2 expression was similar throughout the small intestines but lower in the
      duodenum and distal ileum. pSGLT1 abundance was significantly lower in the ileum
      compared with the jejunum associated with significantly higher glucose-induced
      Isc . SGLT1 phosphorylation was not inducible by Epi. Epi treatment decreased
      glucose-induced Isc and glucose flux rates in the jejunum but increased basal Isc
      in the ileum. Epi-induced PKA activation was detectable in jejunal tissue. These
      results may indicate that SGLT1 phosphorylation at Ser418 represents a structural
      change to compensate for certain conditions that may decrease glucose transport
      (unfavorable driving forces/changed apical membrane potential) rather than being
      the cause for the overall differences in glucose transport characteristics
      between the jejunum and ileum.

PMID- 29333721
TI  - Carbohydrate dose influences liver and muscle glycogen oxidation and performance
      during prolonged exercise.
AB  - This study investigated the effect of carbohydrate (CHO) dose and composition on
      fuel selection during exercise, specifically exogenous and endogenous (liver and
      muscle) CHO oxidation. Ten trained males cycled in a double-blind randomized
      order on 5 occasions at 77% VO2max for 2 h, followed by a 30-min time-trial (TT)
      while ingesting either 60 g.h-1 (LG) or 75 g.h-113 C-glucose (HG), 90 g.h-1 (LGF)
      or 112.5 g.h-113 C-glucose-13 C-fructose ([2:1] HGF) or placebo. CHO doses met or
      exceed reported intestinal transporter saturation for glucose and fructose.
      Indirect calorimetry and stable mass isotope [13 C] tracer techniques were
      utilized to determine fuel use. TT performance was 93% "likely/probable" to be
      improved with LGF compared with the other CHO doses. Exogenous CHO oxidation was
      higher for LGF and HGF compared with LG and HG (ES > 1.34, P < 0.01), with the
      relative contribution of LGF (24.5 +/- 5.3%) moderately higher than HGF (20.6 +/-
      6.2%, ES = 0.68). Increasing CHO dose beyond intestinal saturation increased
      absolute (29.2 +/- 28.6 g.h-1 , ES = 1.28, P = 0.06) and relative muscle glycogen
      utilization (9.2 +/- 6.9%, ES = 1.68, P = 0.014) for glucose-fructose ingestion.
      Absolute muscle glycogen oxidation between LG and HG was not significantly
      different, but was moderately higher for HG (ES = 0.60). Liver glycogen oxidation
      was not significantly different between conditions, but absolute and relative
      contributions were moderately attenuated for LGF (19.3 +/- 9.4 g.h-1 , 6.8 +/-
      3.1%) compared with HGF (30.5 +/- 17.7 g.h-1 , 10.1 +/- 4.0%, ES = 0.79 & 0.98).
      Total fat oxidation was suppressed in HGF compared with all other CHO conditions
      (ES > 0.90, P = 0.024-0.17). In conclusion, there was no linear dose response for
      CHO ingestion, with 90 g.h-1 of glucose-fructose being optimal in terms of TT
      performance and fuel selection.

PMID- 29333722
TI  - Cardiovascular adjustments during anticipated postural changes.
AB  - It is well-documented that feedforward cardiovascular responses occur at the
      onset of exercise, but it is unclear if such responses are associated with other
      types of movements. In this study, we tested the hypothesis that feedforward
      cardiovascular responses occur when a passive (imposed) 60 degrees  head-up tilt
      is anticipated, such that changes in heart rate and carotid artery blood flow
      (CBF) commence prior to the onset of the rotation. A light cue preceded head-up
      tilts by 10 sec, and heart rate and CBF were determined for 5-sec time periods
      prior to and during tilts. Even after these stimuli were provided for thousands
      of trials spanning several months, no systematic changes in CBF and heart rate
      occurred prior to tilts, and variability in cardiovascular adjustments during
      tilt remained substantial over time. We also hypothesized that substitution of 20
      degrees  for 60 degrees  tilts in a subset of trials would result in exaggerated
      cardiovascular responses (as animals expected 60 degrees  tilts), which were not
      observed. These data suggest that cardiovascular adjustments during passive
      changes in posture are mainly elicited by feedback mechanisms, and that
      anticipation of passive head-up tilts does not diminish the likelihood that a
      decrease in carotid blood flow will occur during the movements.

PMID- 29333723
TI  - Nandrolone-induced nuclear accumulation of MyoD protein is mediated by Numb, a
      Notch inhibitor, in C2C12 myoblasts.
AB  - Signaling via the androgen receptor (AR) stimulates myogenic progenitor
      differentiation. In addition, myogenic differentiation factor D (MyoD) and Numb,
      a Notch inhibitor, play key roles in regulating myogenic differentiation.
      Nandrolone, an anabolic steroid, upregulates both MyoD and Numb expression in
      myogenic cells. However, the molecular mechanisms by which MyoD is upregulated by
      nandrolone are unclear. Moreover, the potential crosstalk between nandrolone,
      MyoD, and Numb is not well understood. With these considerations in mind, we
      examined the effects of nandrolone on the expression of MyoD mRNA and protein,
      and determined the interactions of MyoD and Numb in the presence or absence of
      nandrolone in differentiating C2C12 myoblasts. Nandrolone increased MyoD mRNA and
      protein expression and significantly enhanced nuclear translocation of MyoD
      protein. The later effect of nandrolone was blunted by siRNA against Numb.
      Immunoprecipitation (IP) studies confirmed that Numb forms complexes with MyoD.
      Chromatin IP revealed that in the presence of nandrolone, Numb is recruited to a
      region of the MyH7 promotor containing the E-box to which MyoD binds. These data
      indicate that nandrolone-regulated MyoD activation occurs mainly through a
      posttranslational mechanism which promotes MyoD nuclear accumulation, and suggest
      that this effect of nandrolone is, at least in part, mediated by Numb.

PMID- 29333724
TI  - Voluntary activation and twitch potentiation of the elbow flexors across
      supinated, neutral, and pronated forearm orientations.
AB  - Elbow flexion force depends on forearm orientation with supinated and neutral
      being stronger than pronated. The purpose of this study was to assess the
      influence of forearm orientation on voluntary activation (VA), postactivation
      potentiation (PAP), and twitch properties. Eleven males (23 +/- 3 years)
      performed isometric elbow flexion maximal voluntary contractions (MVC) in
      supinated, neutral, and pronated forearm orientations with supramaximal
      stimulation to the biceps brachii muscle belly before, during, and after the MVC.
      MVC and VA were higher in supinated (213.6 +/- 49.6 N; 93.0 +/- 5.2%) and neutral
      (243.6 +/- 48.0 N; 96.1 +/- 3.2%) compared with pronated (113.6 +/- 21.3 N; 70.9
      +/- 20.4%) (P < 0.05), while PAP did not differ across the three orientations
      (71.6 +/- 42.2%) (P > 0.05). In the rested state, pronated peak tension (PT) was
      less compared with supinated (42%). In the potentiated state, pronated PT was
      less than supinated (50%) and neutral (53%) (P < 0.05). Reduced strength in the
      pronated orientation is partially attributed to reduced drive; however,
      reductions in peak tension indicate that there also is a mechanical disadvantage
      when the forearm is placed into a pronated orientation, and this does not alter
      PAP.

PMID- 29333725
TI  - Chemoreflex function and brain blood flow during upright posture in men and
      women.
AB  - Orthostatic intolerance is more common in women than men, and some studies have
      found that women in the early follicular (EF) phase of the menstrual cycle
      experience the greatest feelings of lightheadedness. Chemoreflex function while
      supine or upright was investigated to determine the potential contribution of
      ventilatory control to these phenomena. Men (n = 13) and women (n = 14) were
      tested while supine and 70 degrees  upright (head-up tilt [HUT]) and given: (1)
      normoxia or (2) hypercapnia (5% CO2 ). Women were tested during the EF phase
      (days 2-5) and the midluteal phase (ML; days 18-24). During HUT, all groups
      reduced cerebrovascular resistance index (men: 1.45 +/- 0.08 to 1.42 +/- 0.07
      mmHg/(cm.sec), EF: 1.38 +/- 0.11 to 1.26 +/- 0.10 mmHg/(cm.sec), ML: 1.25 +/-
      0.07 to 1.09 +/- 0.07 mmHg/(cm.sec); P <= 0.019); however, only men increased
      ventilation (men: 11.99 +/- 0.65 to 13.24 +/- 0.83 L/min; P < 0.01). In response
      to hypercapnia in the supine position, men had a smaller increase of diastolic
      middle cerebral artery velocity compared to women in the ML phase (men: +9.1 +/-
      2.0 cm/sec, ML: +15.7 +/- 3.1 cm/sec, P = 0.039). During hypercapnia in HUT
      (compared to hypercapnia while supine), all groups had an augmented increase of
      ventilation (men: +7.46 +/- 1.34 vs. +5.84 +/- 1.09 L/min, EF: +6.71 +/- 0.83 vs.
      +5.48 +/- 0.66 L/min, ML: +7.99 +/- 1.13 vs. +5.65 +/- 0.81 L/min; P <= 0.028),
      suggesting that all groups experienced augmentation of the CO2 chemoreflex;
      however, only men had an augmented increase of mean arterial pressure (+0.10 +/-
      0.58 to +4.71 +/- 0.87 mmHg; P <= 0.017). Our results indicate that men have
      different ventilatory responses to upright tilt compared to women, and that the
      CO2 chemoreflex response is enhanced in upright posture in both sexes.
      Furthermore, sexually dimorphic blood pressure responses to this chemoreflex
      enhancement are evident.

PMID- 29333726
TI  - Calcium current properties in dystrophin-deficient ventricular cardiomyocytes
      from aged mdx mice.
AB  - Duchenne muscular dystrophy (DMD), caused by mutations in the gene encoding for
      the cytoskeletal protein dystrophin, is linked with severe cardiac complications
      including cardiomyopathy development and cardiac arrhythmias. We and others
      recently reported that currents through L-type calcium (Ca) channels were
      significantly increased, and channel inactivation was reduced in dystrophin
      deficient ventricular cardiomyocytes derived from the mdx mouse, the most
      commonly used animal model for human DMD. These gain-of-function Ca channel
      abnormalities may enhance the risk of Ca-dependent arrhythmias and cellular Ca
      overload in the dystrophic heart. All studies, which have so far investigated L
      type Ca channel properties in dystrophic cardiomyocytes, have used hearts from
      either neonatal or young adult mdx mice as cell source. In consequence, the
      dimension of the Ca channel abnormalities present in the severely-diseased aged
      dystrophic heart has remained unknown. Here, we have studied potential
      abnormalities in Ca currents and intracellular Ca transients in ventricular
      cardiomyocytes derived from aged dystrophic mdx mice. We found that both the L
      type and T-type Ca current properties of mdx cardiomyocytes were similar to those
      of myocytes derived from aged wild-type mice. Accordingly, Ca release from the
      sarcoplasmic reticulum was normal in cardiomyocytes from aged mdx mice. This
      suggests that, irrespective of the presence of a pronounced cardiomyopathy in
      aged mdx mice, Ca currents and Ca release in dystrophic cardiomyocytes are
      normal. Finally, our data imply that dystrophin- regulation of L-type Ca channel
      function in the heart is lost during aging.

PMID- 29333727
TI  - The relation between maximal voluntary force in m. palmaris longus and the
      temporal and spatial summation of muscle fiber recruitment in human subjects.
AB  - This study aimed at looking at the frequency (T-score) and the amplitude (S
      score) of fiber use during contraction of a forearm muscle, m. palmaris longus,
      as measured by acoustic myography (AMG). An additional aim was to relate the T-
      and S-scores to the recorded force obtained from a hand dynamometer. The
      hypothesis being that temporal and spatial summation of muscle fiber contraction
      in a given muscle during a given movement, can together describe a given obtained
      force. Force measurements were carried out on 12 healthy human subjects aged 19
      68 years (6 men & 6 women), while their m. palmaris longus contractile function
      was measured using an acoustic myography CURO device. Force production was varied
      from 90 to 10% of assessed maximal voluntary force (MVF), and also monitored over
      a 1 min period of 50% MVF. Linear regression analysis was applied to relate force
      to spatial and temporal summation. Muscle strength was sustained by changing the
      frequency and/or the number of active fibere at any given point in time. Force
      production, whilst stronger for men than women, was regulated in a similar
      fashion for both sexes and was closely correlated with the AMG T- and S-scores.
      It is concluded that AMG is a noninvasive method which can be readily applied to
      accurately describe how a subject uses a given muscle during any given movement.
      These findings have relevance when considering training strategies in subjects
      with muscle trauma or disease, in the elderly, or for both amateur and top
      professional athletes.

PMID- 29333728
TI  - Population correlations do not support the existence of set points for blood
      levels of calcium or glucose - a new model for homeostasis.
AB  - The prevailing teaching regarding homeostasis, and in particular endocrine
      homeostasis, includes the fundamental concept of a "set point," which represents
      a target or optimum level defended by physiological control mechanisms. Analogies
      for the description and teaching of this concept have included thermostats and
      cruise controls. We previously demonstrated that such a set-point model of
      regulation implies that in population data of parameter set point/controlling
      hormone levels, correlations between the parameter and its controlling hormone
      must be in the direction of the response of the parameter to its controlling
      hormone, and that in thyroid homeostasis this relationship is not observed. In
      this work we similarly examined population correlations, extracted from the
      literature, for the parameters glucose and calcium, and their controlling
      hormones. We found 10 correlations. Most were highly significant (P < 0.01). All
      were in the direction of the response of the controlling hormone to the
      parameter. Therefore, none were consistent with the pattern implied by a set
      point model of regulation. Instead all were consistent with an "equilibrium
      point" model of regulation, whereby ambient levels have no particular connotation
      to the individual, and result passively from the interplay of physiological
      processes. We conclude that glucose and calcium regulation, like thyroid
      regulation, are not centered on set points. This may reflect a general property
      of homeostasis. We provide an alternative mechanistic analogy, without a set
      point, for the heuristic description and teaching, of homeostasis.

PMID- 29333729
TI  - Immunoengineering with biomaterials for enhanced cancer immunotherapy.
AB  - Cancer immunotherapy has recently shown dramatic clinical success inducing
      durable response in patients of a wide variety of malignancies. Further
      improvement of the clinical outcome with immune related cancer treatment requests
      more exquisite manipulation of a patient's immune system with increased immunity
      against diseases while mitigating the toxicities. To meet this challenge,
      biomaterials applied to immunoengineering are being developed to achieve tissue-
      and/or cell-specific immunomodulation and thus could potentially enhance both the
      efficacy and safety of current cancer immunotherapies. Here, we review the recent
      advancement in the field of immunoengineering using biomaterials and their
      applications in promoting different modalities of cancer immunotherapies, with
      focus on cell-, antibody-, immunomodulator-, and gene-based immune related
      treatments and their combinations with conventional therapies. Challenges and
      opportunities are discussed in applying biomaterials engineering strategies in
      the development of future cancer immunotherapies. This article is categorized
      under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic
      Disease Therapeutic Approaches and Drug Discovery > Emerging Technologies
      Implantable Materials and Surgical Technologies > Nanomaterials and Implants.

PMID- 29333730
TI  - Day-to-day mastery and self-efficacy changes during a smoking quit attempt: Two
      studies.
AB  - OBJECTIVE: In social-cognitive theory, it is hypothesized that mastery
      experiences (successfully implementing behaviour change) are a source of self
      efficacy, and self-efficacy increases the opportunity for experiencing mastery.
      Vicarious experiences (seeing others succeed) are suggested as another source of
      self-efficacy. However, the hypothesis of this reciprocal relationship has not
      been tested using a day-to-day design. DESIGN: This article reports findings from
      two intensive longitudinal studies, testing the reciprocal relationship of self
      efficacy and its two main sources within the naturally occurring process of
      quitting smoking (without intervention). Smokers (Study 1: N = 100 smokers in
      smoker-non-smoker couples (1,787 observations); Study 2; N = 81 female (1,401
      observations) and N = 79 male smokers (1,328 observations) in dual-smoker
      couples) reported their mastery experiences (not smoking the entire day; in Study
      2, mastery experience of partner served as vicarious experience) and smoking
      specific self-efficacy for 21 days after a self-set quit date. METHODS: Time
      lagged multilevel analyses were conducted using change-predicting-change models.
      RESULTS: Increases in mastery experiences predicted changes in self-efficacy, and
      increases in self-efficacy predicted changes in mastery experiences in Study 1.
      Study 2 replicated these results and showed contagion effects (partners' mastery
      on individuals' mastery and partners' self-efficacy on individuals' self
      efficacy), but found no evidence for a link between vicarious experiences
      (partners' mastery experiences) and individuals' self-efficacy. CONCLUSIONS: This
      article demonstrates that mastery experiences and self-efficacy show a reciprocal
      relationship within smokers during a quit attempt in a day-to-day design, as well
      as contagion effects in couples when both partners try to quit simultaneously.
      Statement of Contribution What is already known on this subject? Self-efficacy is
      one of the strongest correlates of quitting smoking. Despite the assumptions on
      how self-efficacy is built formulated by Bandura two decades ago, there is only
      little empirical evidence on the origins of self-efficacy. The open research
      questions for these two studies were whether mastery experiences (experiencing
      success with the new behavior) and vicarious experiences (seeing others succeed)
      facilitate the smoking cessation process, whether mastery experiences and self
      efficacy affect one another reciprocally and whether intimate partners serve as
      role models for each other. What does this study add? Mastery experiences and
      self-efficacy are mutually depended on a day-to-day basis within the smoking
      cessation process. Effects of mastery experiences fade rapidly, indicating that
      constant successes are needed to keep up self-efficacy. Dual-smoker couples show
      similar changes in a contagious way - if mastery experiences increase in one
      person, mastery experiences increase in the partner; if self-efficacy increases
      in one person, self-efficacy increases in the partner, too. No support for
      vicarious experiences (mastery experiences in one person affecting self-efficacy
      in the partner and vice versa) as sources of self-efficacy in the quitting
      process was found.

PMID- 29333731
TI  - William G. Bradley, Jr, MD, PhD, FACR (1942-2017).

PMID- 29333732
TI  - Artificial intelligence will reduce the need for clinical medical physicists.

PMID- 29333733
TI  - State of the JACMP.

PMID- 29333734
TI  - Synthesis, Cytotoxic, and Antibacterial Evaluation of Quinazolinone Derivatives
      with Substituted Amino Moiety.
AB  - A series of novel quinazolinone derivatives containing a substituted amino moiety
      were synthesized, evaluated for their cytotoxic and antibacterial activities. The
      results of MTT assay showed that all synthesized target compounds 5A - 5O showed
      potent cytotoxicity against SGC-7901 (IC50 , 0.72 - 1.41 MUm). Moreover, the
      compounds 5D, 5I, and 5K showed better selectivity as compared with positive
      controls pemetrexed and MTX due to weak cytotoxicity against normal tissue cell
      line HUVSMC. Among synthesized compounds, the compounds 5E, 5J, 5L, and 5N showed
      broad-spectrum cytotoxic activities against at least four cancer cell lines at a
      micromolar level. The results of antibacteria evaluation revealed that all
      synthesized compounds showed good to moderate antibacterial activities against
      Gram-negative bacteria Escherichia coli. Among them, the MIC values of the
      compounds 5C, 5F, and 5M were 0.31 MUg/mL.

PMID- 29333735
TI  - Hot-Electron-Assisted Femtosecond All-Optical Modulation in Plasmonics.
AB  - The optical Kerr nonlinearity of plasmonic metals provides enticing prospects for
      developing reconfigurable and ultracompact all-optical modulators. In
      nanostructured metals, the coherent coupling of light energy to plasmon
      resonances creates a nonequilibrium electron distribution at an elevated electron
      temperature that gives rise to significant Kerr optical nonlinearities. Although
      enhanced nonlinear responses of metals facilitate the realization of efficient
      modulation devices, the intrinsically slow relaxation dynamics of the
      photoexcited carriers, primarily governed by electron-phonon interactions,
      impedes ultrafast all-optical modulation. Here, femtosecond (~190 fs) all-optical
      modulation in plasmonic systems via the activation of relaxation pathways for hot
      electrons at the interface of metals and electron acceptor materials, following
      an on-resonance excitation of subradiant lattice plasmon modes, is demonstrated.
      Both the relaxation kinetics and the optical nonlinearity can be actively tuned
      by leveraging the spectral response of the plasmonic design in the linear regime.
      The findings offer an opportunity to exploit hot-electron-induced nonlinearities
      for design of self-contained, ultrafast, and low-power all-optical modulators
      based on plasmonic platforms.

PMID- 29333736
TI  - Underestimated caregiver burden by cancer patients and its association with
      quality of life, depression and anxiety among caregivers.
AB  - This study examined how patients with cancer estimate caregiver burden (CB) and
      the association between their underestimation of CB and their caregivers' self
      ratings of their quality of life (CQOLC-K; Korean version of the Caregiver
      Quality of Life Index-Cancer), depression and anxiety (Korean version of the
      Hospital Anxiety and Depression Scale). Participants consisted of 990 patient
      caregiver dyads recruited from a nationwide cross-sectional survey conducted in
      South Korea. Medical baseline data were retrieved from the hospital information
      systems of the participating centres. The patients with cancer who underestimated
      CB ranged from 18.62% (for physical CB) to 23.33% (for social CB). They had less
      advanced cancer, a lower income, were the caregiver's spouse, reported higher
      levels of family avoidance of communication about cancer, and had female
      caregivers. The patients' underestimation of CB was significantly related to
      lower CQoL and higher levels of caregiver depression and anxiety. The current
      study provides empirical evidence for the link between the underestimation of CB
      by patients with cancer and compromised caregiving experiences of cancer
      caregivers. Open family communication about cancer was discussed as one of
      several practical strategies for decreasing patients' underestimation of CB.

PMID- 29333737
TI  - Recent advances in veterinary radiation oncology.

PMID- 29333738
TI  - Antibacterial and Antifungal Activity of Poly(Lactic Acid)-Bovine Lactoferrin
      Nanofiber Membranes.
AB  - Antimicrobial materials have become relevant for local therapies preventing
      microbial resistance induced by systemic antibiotic treatments. This work reports
      the development of electrospun poly(lactic acid) (PLLA) nanofiber membranes
      loaded with bovine lactoferrin (bLF) up to 20 wt%. The membranes present smooth
      and nondefective fibers with mean diameters between 717 +/- 197 and 495 +/- 127
      nm, and an overall porosity of ~80%. The hydrophobicity of the PLLA membranes is
      reduced by the presence of bLF. The release profile of bLF correlates with an
      anomalous transport model, with 17.7 +/- 3.6% being released over 7 weeks. The
      nanofiber mats show no cytotoxicity on human skin fibroblasts and even promote
      cell proliferation after short exposure periods. Furthermore, the developed
      membranes display antifungal activity against Aspergillus nidulans by inhibiting
      spore germination and mycelial growth. These results evidence the strong
      potential of bLF-PLLA nanofiber membranes to be used as antifungal dressings.

PMID- 29333739
TI  - Nickel-Based (Photo)Electrocatalysts for Hydrogen Production.
AB  - Hydrogen is considered a promising energy carrier for replacing traditional
      fossil fuels. Electrochemical or solar-driven water splitting is a green and
      sustainable method of producing hydrogen. To lower the overpotential and minimize
      energy costs, numerous reports have focused on developing noble-metal-free
      catalysts for hydrogen production, with special attention paid to nickel-based
      materials. Herein, the current state of research on the use of Ni-based materials
      as electrocatalysts, cocatalysts, and photoactive materials in hydrogen
      production is reviewed. Recent research efforts toward the development of various
      Ni-based (photo)electrocatalysts, their applications in hydrogen production, and
      the corresponding mechanisms are covered. The approaches used to improve or
      optimize these materials are summarized, and the key remaining challenges are
      discussed.

PMID- 29333740
TI  - Pharmacokinetics, disposition, and plasma concentrations of dimethyl sulfoxide
      (DMSO) in the horse following topical, oral, and intravenous administration.
AB  - Compartmental models were used to investigate the pharmacokinetics of intravenous
      (i.v.), oral (p.o.), and topical (TOP) administration of dimethyl sulfoxide
      (DMSO). The plasma concentration-time curve following a 15-min i.v. infusion of
      DMSO was described by a two-compartment model. Median and range of alpha
      (t1/2alpha ) and beta (t1/2beta ) half-lives were 0.029 (0.026-0.093) and 14.1
      (6.6-16.4) hr, respectively. Plasma concentration-time curves of DMSO following
      p.o. and TOP administration were best described by one-compartment absorption and
      elimination models. Following the p.o. administration, median absorption (t1/2ab
      ) and elimination (t1/2e ) half-lives were 0.15 (0.01-0.77) and 15.5 (8.5-25.2)
      hr, respectively. The plasma concentrations of DMSO were 47.4-129.9 MUg/ml,
      occurring between 15 min and 4 hr. The fractional absorption (F) during a 24-hr
      period was 47.4 (22.7-98.1)%. Following TOP administrations, the median t1/2ab
      and t1/2e were 1.2 (0.49-2.3) and 4.5 (2.1-11.0) hr, respectively. Plasma
      concentrations were 1.2-8.2 MUg/ml occurring at 2-4 hr. Fractional absorption
      following TOP administration was 0.48 (0.315-4.4)% of the dose administered.
      Clearance (Cl) of DMSO following the i.v. administration was 3.2 (2.2-6.7) ml hr
      1  kg-1 . The corrected clearances (ClF ) for p.o. and TOP administrations were
      2.9 (1.1-5.5) and 4.5 (0.52-18.2) ml hr-1  kg-1 .

PMID- 29333741
TI  - P-Type Low-Molecular-Weight Hydrogelators.
AB  - As the use of low-molecular-weight gelators (LMWGs) as components in single and
      multicomponent systems for optoelectronic and solar cell applications increases,
      so does the need for more functional gelators. There are relatively few examples
      of p-type gelators that can be used in such systems. Here, the synthesis and
      characterization of three amino-acid-functionalized p-type gelators based on
      terthiophene, tetrathiafulvalene, and oligo(phenylenevinylene) are described. The
      cores of these molecules are already used as electron donors in optoelectronic
      applications. These newly designed molecules can gel water to form highly
      organized structures, which can be dried into thin films that show p-type
      behavior.

PMID- 29333743
TI  - Dyadic coping and marital adjustment during pregnancy: A cross-sectional study of
      Italian couples expecting their first child.
AB  - Although the transition to parenthood is currently defined as a normative event,
      it can be potentially stressful for the couple relationship as it may contribute
      to psychological distress and reduced marital satisfaction. Using the systemic
      transactional conceptualisation of stress and coping as a theoretical framework,
      we claimed that the ability of the parents-to-be to adjust to their new roles and
      identity is influenced by dyadic coping strategies. This study examined the
      effects of dyadic coping on marital adjustment in a sample of 78 primiparous
      couples. Women and partners completed the Dyadic Adjustment Scale and the Dyadic
      Coping Questionnaire during late pregnancy. Data were analysed using the Actor
      Partner Interdependence Model. Results revealed that both women and partners'
      scores on positive dyadic coping behaviours contributed to higher marital
      adjustment, suggesting that risks for marital dissatisfaction may exist for
      couples not able to implement adaptive dyadic coping strategies, or for those
      unsatisfied with the implemented coping behaviours.

PMID- 29333744
TI  - High-Performance Organic Bulk-Heterojunction Solar Cells Based on Multiple-Donor
      or Multiple-Acceptor Components.
AB  - Organic solar cells (OSCs) based on bulk heterojunction structures are promising
      candidates for next-generation solar cells. However, the narrow absorption
      bandwidth of organic semiconductors is a critical issue resulting in insufficient
      usage of the energy from the solar spectrum, and as a result, it hinders
      performance. Devices based on multiple-donor or multiple-acceptor components with
      complementary absorption spectra provide a solution to address this issue. OSCs
      based on multiple-donor or multiple-acceptor systems have achieved power
      conversion efficiencies over 12%. Moreover, the introduction of an additional
      component can further facilitate charge transfer and reduce charge recombination
      through cascade energy structure and optimized morphology. This progress report
      provides an overview of the recent progress in OSCs based on multiple-donor
      (polymer/polymer, polymer/dye, and polymer/small molecule) or multiple-acceptor
      (fullerene/fullerene, fullerene/nonfullerene, and nonfullerene/nonfullerene)
      components.

PMID- 29333742
TI  - Parvalbumin fast-spiking interneurons are selectively altered by paediatric
      traumatic brain injury.
AB  - KEY POINTS: Traumatic brain injury (TBI) in children remains a leading cause of
      death and disability and it remains poorly understood why children have worse
      outcomes and longer recover times. TBI has shown to alter cortical excitability
      and inhibitory drive onto excitatory neurons, yet few studies have directly
      examined changes to cortical interneurons. This is addressed in the present study
      using a clinically relevant model of severe TBI (controlled cortical impact) in
      interneuron cell type specific Cre-dependent mice. Mice subjected to controlled
      cortical impact exhibit specific loss of parvalbumin (PV) but not somatostatin
      immunoreactivity and cell density in the peri-injury zone. PV interneurons are
      primarily of a fast-spiking (FS) phenotype that persisted in the peri-injury zone
      but received less frequent inhibitory and stronger excitatory post-synaptic
      currents. The targeted loss of PV-FS interneurons appears to be distinct from
      previous reports in adult mice suggesting that TBI-induced pathophysiology is
      dependent on the age at time of impact. ABSTRACT: Paediatric traumatic brain
      injury (TBI) is a leading cause of death and disability in children.
      Traditionally, ongoing neurodevelopment and neuroplasticity have been considered
      to confer children with an advantage following TBI. However, recent findings
      indicate that the paediatric brain may be more sensitive to brain injury.
      Inhibitory interneurons are essential for proper cortical function and are
      implicated in the pathophysiology of TBI, yet few studies have directly
      investigated TBI-induced changes to interneurons themselves. Accordingly, in the
      present study, we examine how inhibitory neurons are altered following controlled
      cortical impact (CCI) in juvenile mice with targeted Cre-dependent fluorescence
      labelling of interneurons (Vgat:Cre/Ai9 and PV:Cre/Ai6). Although CCI failed to
      alter the number of excitatory neurons or somatostatin-expressing interneurons in
      the peri-injury zone, it significantly decreased the density of parvalbumin (PV)
      immunoreactive cells by 71%. However, PV:Cre/Ai6 mice subjected to CCI showed a
      lower extent of fluorescence labelled cell loss. PV interneurons are
      predominantly of a fast-spiking (FS) phenotype and, when recorded
      electrophysiologically from the peri-injury zone, exhibited intrinsic properties
      similar to those of control neurons. Synaptically, CCI induced a decrease in
      inhibitory drive onto FS interneurons combined with an increase in the strength
      of excitatory events. The results of the present study indicate that CCI induced
      both a loss of PV interneurons and an even greater loss of PV expression. This
      suggests caution is required when interpreting changes in PV immunoreactivity
      alone as direct evidence of interneuronal loss. Furthermore, in contrast to
      reports in adults, TBI in the paediatric brain selectively alters PV-FS
      interneurons, primarily resulting in a loss of interneuronal inhibition.

PMID- 29333745
TI  - Increased sensitivity and high specificity of indirect immunofluorescence in
      detecting IgG subclasses for diagnosis of bullous pemphigoid.
AB  - BACKGROUND: Indirect immunofluorescence (IIF) microscopy on monkey oesophagus is
      an important assay for the diagnosis of bullous pemphigoid (BP). Its relatively
      low sensitivity (60-80%) may be partly due to insufficient detection of minor IgG
      subclasses. AIM: To determine the operating characteristics of an IgG subclass in
      IIF. METHODS: We designed a retrospective, dual-centre, controlled cohort study
      on sera from 64 BP sera that had been rated as false negatives by traditional IIF
      microscopy, and assessed circulating IgG1 , IgG3 and IgG4 autoantibodies.
      RESULTS: The sensitivities of IIF in detecting IgG1 , IgG3 , IgG4 and all three
      in combination were 45.3%, 18.8%, 32.8% and 48.4%, respectively. Specificities
      were > 97%. CONCLUSION: Detection of IgG subclass (especially IgG1 and IgG4 )
      autoantibodies by IIF on monkey oesophagus can significantly improve diagnostic
      performance of IIF microscopy for diagnosis of BP.

PMID- 29333746
TI  - Novel KIT variants for dominant white in the Australian horse population.

PMID- 29333747
TI  - Rapid, Regioselective Living Ring-Opening Metathesis Polymerization of Bio
      Derivable Asymmetric Tricyclic Oxanorbornenes.
AB  - The synthesis of a range of alkyl esters (methyl, n-butyl, and n-decyl) prepared
      via Steglich esterification of the thermodynamically controlled exo, exo Diels
      Alder adduct of furfuryl alcohol and maleic anhydride is reported. Subsequent
      ring-opening metathesis polymerization of these bio-derivable tricyclic
      oxanorbornene analogs delivers polymers with targeted molar mass and low molar
      mass dispersity. The polymerizations are rapid with complete monomer conversion
      achieved within 15 min. Significantly, the presence of the cyclic lactone at the
      bridgehead of these monomers leads to polymers with high regioregularity (>85%
      head-to-tail) and high stereoregularity (>75% trans). The resultant polymers
      display both high thermal stability and high glass transition temperatures. This
      new class of oxanorbornene monomer, accessed from bio-derivable furfuryl alcohol
      and maleic anhydride, may be further tailored to incorporate a range of
      functional moieties. Furthermore, the exceptional properties of the derived
      polymers indicate potential in a range of applications.

PMID- 29333748
TI  - Near-Infrared Light-Sensitive Polyvinyl Alcohol Hydrogel Photoresist for
      Spatiotemporal Control of Cell-Instructive 3D Microenvironments.
AB  - Advanced hydrogel systems that allow precise control of cells and their 3D
      microenvironments are needed in tissue engineering, disease modeling, and drug
      screening. Multiphoton lithography (MPL) allows true 3D microfabrication of
      complex objects, but its biological application requires a cell-compatible
      hydrogel resist that is sufficiently photosensitive, cell-degradable, and
      permissive to support 3D cell growth. Here, an extremely photosensitive cell
      responsive hydrogel composed of peptide-crosslinked polyvinyl alcohol (PVA) is
      designed to expand the biological applications of MPL. PVA hydrogels are formed
      rapidly by ultraviolet light within 1 min in the presence of cells, providing
      fully synthetic matrices that are instructive for cell-matrix remodeling,
      multicellular morphogenesis, and protease-mediated cell invasion. By focusing a
      multiphoton laser into a cell-laden PVA hydrogel, cell-instructive extracellular
      cues are site-specifically attached to the PVA matrix. Cell invasion is thus
      precisely guided in 3D with micrometer-scale spatial resolution. This robust
      hydrogel enables, for the first time, ultrafast MPL of cell-responsive synthetic
      matrices at writing speeds up to 50 mm s-1 . This approach should enable facile
      photochemical construction and manipulation of 3D cellular microenvironments with
      unprecedented flexibility and precision.

PMID- 29333750
TI  - Hydroperoxide Traces in Common Cyclic Ethers as Initiators for Controlled RAFT
      Polymerizations.
AB  - Herein, a reversible addition-fragmentation chain transfer (RAFT) polymerization
      is introduced for reactive monomers like N-acryloylpyrrolidine or N,N
      dimethylacrylamide working without a conventional radical initiator. As a very
      straightforward proof of principle, the method takes advantage of the usually
      inconvenient radical-generating hydroperoxide contaminations in cyclic ethers
      like tetrahydrofuran or 1,4-dioxane, which are very common solvents in polymer
      sciences. The polymerizations are surprisingly well controlled and the polymers
      can be extended with a second block, indicating their high livingness. "Solvent
      initiated" RAFT polymerizations hence prove to be a feasible access to tailored
      materials with minimal experimental effort and standard laboratory equipment,
      only requiring the following ingredients: hydroperoxide-contaminated solvent,
      monomer, and RAFT agent. In other respects, however, the potential coinitiating
      ability of the used solvent is to be considered when investigating the kinetics
      of RAFT polymerizations or aiming for the synthesis of high-livingness polymers,
      e.g., multiblock copolymers.

PMID- 29333749
TI  - Tetralogy of Fallot with left ventricular clot.

PMID- 29333751
TI  - Identification of the Minimal Glycotope of Streptococcus pneumoniae 7F Capsular
      Polysaccharide using Synthetic Oligosaccharides.
AB  - Streptococcus pneumoniae causes life-threatening diseases including meningitis,
      pneumonia and sepsis. Existing glycoconjugate vaccines based on purified capsular
      polysaccharides are widely used and help to prevent millions of deaths every
      year. Herein, the total syntheses of oligosaccharides resembling portions of the
      S. pneumoniae serotype 7F (ST7F) capsular polysaccharide repeating unit are
      reported. To define minimal glycan epitopes, glycan microarrays containing the
      synthetic oligosaccharides were used to screen human reference serum and revealed
      that both side chains of the ST7F play a key role in antigen recognition. The
      identification of protective minimal epitopes is vital to design efficient semi-
      and fully-synthetic glycoconjugate vaccines.

PMID- 29333752
TI  - Workplace design for the Australian residential aged care workforce.
AB  - OBJECTIVES: This research explored residential aged care (RAC) workplace design
      features that influence how RAC staff feel valued, productive, safe, like they
      belong and connected. A secondary aim was to validate emerging themes about RAC
      design features with stakeholders. METHODS: A multistage qualitative study was
      conducted in one RAC facility with 100 residents in outer metropolitan Melbourne:
      (i) photo-elicitation - photographs were used to prompt discussions with RAC
      staff; (ii) individual interviews with RAC directors; and (iii) validity testing
      with the advisory committee occurred. RESULTS: Key workplace design features that
      influenced how RAC staff feel valued, productive, safe, like they belong and
      connected included the following: (i) home-like environment; (ii) access to
      outdoor spaces; (iii) quality indoor environment; and (iv) access to safe, open
      and comfortable workplaces. CONCLUSIONS: Key workplace design features that
      matter to RAC staff in a 'shared workspace' exist. Increasing demands upon RAC
      requires evidence-based workplace design policy and evaluation approaches that
      support RAC staff to work in RAC shared workspaces.

PMID- 29333753
TI  - Comparative performance of different scale-down simulators of substrate gradients
      in Penicillium chrysogenum cultures: the need of a biological systems response
      analysis.
AB  - In a 54 m3 large-scale penicillin fermentor, the cells experience substrate
      gradient cycles at the timescales of global mixing time about 20-40 s. Here, we
      used an intermittent feeding regime (IFR) and a two-compartment reactor (TCR) to
      mimic these substrate gradients at laboratory-scale continuous cultures. The IFR
      was applied to simulate substrate dynamics experienced by the cells at full scale
      at timescales of tens of seconds to minutes (30 s, 3 min and 6 min), while the
      TCR was designed to simulate substrate gradients at an applied mean residence
      time (tauc) of 6 min. A biological systems analysis of the response of an
      industrial high-yielding P. chrysogenum strain has been performed in these
      continuous cultures. Compared to an undisturbed continuous feeding regime in a
      single reactor, the penicillin productivity (qPenG ) was reduced in all scale
      down simulators. The dynamic metabolomics data indicated that in the IFRs, the
      cells accumulated high levels of the central metabolites during the feast phase
      to actively cope with external substrate deprivation during the famine phase. In
      contrast, in the TCR system, the storage pool (e.g. mannitol and arabitol)
      constituted a large contribution of carbon supply in the non-feed compartment.
      Further, transcript analysis revealed that all scale-down simulators gave
      different expression levels of the glucose/hexose transporter genes and the
      penicillin gene clusters. The results showed that qPenG did not correlate well
      with exposure to the substrate regimes (excess, limitation and starvation), but
      there was a clear inverse relation between qPenG and the intracellular glucose
      level.

PMID- 29333755
TI  - Writing: be mindful of context.

PMID- 29333754
TI  - A guide to analysis and reconstruction of serial block face scanning electron
      microscopy data.
AB  - Serial block face scanning electron microscopy (SBF-SEM) is a relatively new
      technique that allows the acquisition of serially sectioned, imaged and digitally
      aligned ultrastructural data. There is a wealth of information that can be
      obtained from the resulting image stacks but this presents a new challenge for
      researchers - how to computationally analyse and make best use of the large
      datasets produced. One approach is to reconstruct structures and features of
      interest in 3D. However, the software programmes can appear overwhelming, time
      consuming and not intuitive for those new to image analysis. There are a limited
      number of published articles that provide sufficient detail on how to do this
      type of reconstruction. Therefore, the aim of this paper is to provide a detailed
      step-by-step protocol, accompanied by tutorial videos, for several types of
      analysis programmes that can be used on raw SBF-SEM data, although there are more
      options available than can be covered here. To showcase the programmes, datasets
      of skeletal muscle from foetal and adult guinea pigs are initially used with
      procedures subsequently applied to guinea pig cardiac tissue and locust brain.
      The tissue is processed using the heavy metal protocol developed specifically for
      SBF-SEM. Trimmed resin blocks are placed into a Zeiss Sigma SEM incorporating the
      Gatan 3View and the resulting image stacks are analysed in three different
      programmes, Fiji, Amira and MIB, using a range of tools available for
      segmentation. The results from the image analysis comparison show that the
      analysis tools are often more suited to a particular type of structure. For
      example, larger structures, such as nuclei and cells, can be segmented using
      interpolation, which speeds up analysis; single contrast structures, such as the
      nucleolus, can be segmented using the contrast-based thresholding tools. Knowing
      the nature of the tissue and its specific structures (complexity, contrast, if
      there are distinct membranes, size) will help to determine the best method for
      reconstruction and thus maximize informative output from valuable tissue.

PMID- 29333756
TI  - Medical students should know their limitations.

PMID- 29333757
TI  - Optimising workplace-based assessment.

PMID- 29333758
TI  - Benefit of team over individual near-peer teachers.

PMID- 29333759
TI  - Responding to student preferences: a balancing act.

PMID- 29333760
TI  - Supporting medical students with disabilities.

PMID- 29333761
TI  - Simulated patients uncovered.

PMID- 29333762
TI  - Pemphigus herpetiformis with autoantibodies to desmocollins 1, 2 and 3.

PMID- 29333763
TI  - Polymer-Passivated Inorganic Cesium Lead Mixed-Halide Perovskites for Stable and
      Efficient Solar Cells with High Open-Circuit Voltage over 1.3 V.
AB  - Cesium-based trihalide perovskites have been demonstrated as promising light
      absorbers for photovoltaic applications due to their superb composition
      stability. However, the large energy losses (Eloss ) observed in inorganic
      perovskite solar cells has become a major hindrance impairing the ultimate
      efficiency. Here, an effective and reproducible method of modifying the interface
      between a CsPbI2 Br absorber and polythiophene hole-acceptor to minimize the
      Eloss is reported. It is demonstrated that polythiophene, deposited on the top of
      CsPbI2 Br, can significantly reduce electron-hole recombination within the
      perovskite, which is due to the electronic passivation of surface defect states.
      In addition, the interfacial properties are improved by a simple annealing
      process, leading to significantly reduced energy disorder in polythiophene and
      enhanced hole-injection into the hole-acceptor. Consequently, one of the highest
      power conversion efficiency (PCE) of 12.02% from a reverse scan in inorganic
      mixed-halide perovskite solar cells is obtained. Modifying the perovskite films
      with annealing polythiophene enables an open-circuit voltage (VOC ) of up to 1.32
      V and Eloss of down to 0.5 eV, which both are the optimal values reported among
      cesium-lead mixed-halide perovskite solar cells to date. This method provides a
      new route to further improve the efficiency of perovskite solar cells by
      minimizing the Eloss .

PMID- 29333765
TI  - Ultrathin FeOOH Nanolayers with Abundant Oxygen Vacancies on BiVO4 Photoanodes
      for Efficient Water Oxidation.
AB  - Photoelectrochemical (PEC) water splitting is a promising method for storing
      solar energy in the form of hydrogen fuel, but it is greatly hindered by the
      sluggish kinetics of the oxygen evolution reaction (OER). Herein, a facile
      solution impregnation method is developed for growing ultrathin (2 nm) highly
      crystalline beta-FeOOH nanolayers with abundant oxygen vacancies on BiVO4
      photoanodes. These exhibited a remarkable photocurrent density of 4.3 mA cm-2 at
      1.23 V (vs. reversible hydrogen electrode (RHE), AM 1.5 G), which is
      approximately two times higher than that of amorphous FeOOH fabricated by
      electrodeposition. Systematic studies reveal that the excellent PEC activity
      should be attributed to their ultrathin crystalline structure and abundant oxygen
      vacancies, which could effectively facilitate the hole transport/trapping and
      provide more active sites for water oxidation.

PMID- 29333764
TI  - Education is the strongest socio-economic predictor of smoking in pregnancy.
AB  - AIMS: To investigate socio-economic disparities in smoking in pregnancy (SIP) by
      the mother's education, occupational class and current economic conditions.
      DESIGN: Cross-sectional analysis with linked survey and register data. SETTING:
      South-western Finland. PARTICIPANTS: A total of 2667 pregnant women [70% of the
      original sample (n = 3808)] from FinnBrain, a prospective pregnancy cohort study.
      MEASUREMENTS: The outcome was smoking during the first pregnancy trimester,
      measured from the Finnish Medical Birth Register. Education and occupational
      class were linked from population registers. Income support recipiency and
      subjective economic wellbeing were questionnaire-based measures of current
      economic conditions. These were adjusted for age, partnership status, residential
      area type, parental separation, parity, childhood socio-economic background,
      childhood adversities (the Trauma and Distressing Events During Childhood scale)
      and antenatal stress (Edinburgh Postnatal Depression Scale). Logistic regressions
      and attributable fractions (AF) were estimated. FINDINGS: Mother's education was
      the strongest socio-economic predictor of SIP. Compared with university
      education, adjusted odds ratios (aORs) of SIP were: 2.2 [95% confidence interval
      (CI) = 1.2-3.9; P = 0.011] for tertiary vocational education, 4.4 (95% CI = 2.1
      9.0; P < 0.001) for combined general and vocational secondary education, 2.9 (95%
      CI = 1.4-6.1; P = 0.006) for general secondary education, 9.5 (95% CI 5.0-18.2; P
      < 0.001) for vocational secondary education and 14.4 (95% CI = 6.3-33.0; P <
      0.001) for compulsory schooling. The total AF of education was 0.5. Adjusted for
      the other variables, occupational class and subjective economic wellbeing did not
      predict SIP. Income support recipiency was associated positively with SIP (aOR =
      1.8; 95% CI = 1.1-3.1; P = 0.022). Antenatal stress predicted SIP (aOR = 2.0; 95%
      CI = 1.4-2.8; P < 0.001), but did not attenuate its socio-economic disparities.
      CONCLUSIONS: In Finland, socio-economic disparities in smoking in pregnancy are
      attributable primarily to differences in the mother's educational level (low
      versus high) and orientation (vocational versus general).

PMID- 29333767
TI  - [Clinical applications of periodontal gingival surgery.I: autogenous grafts].
AB  - The field of periodontics has become increasingly discussed and advanced in
      recent decades. The techniques of periodontal soft tissue grafts are among these
      advancements. The techniques have been used more and more clinically not only in
      periodontics, but also in the areas of dental implantology, aesthetics, and
      orthodontics. In this article, we discuss the clinical indications and the
      advantages and disadvantages of several autogenous tissue grafts (e.g. pedical
      grafts, free gingival graft, and subepithelial connective tissue graft). These
      techniques have made root coverage and the rebuilding of attached gingival
      possible; therefore, it is necessary for all dentists to understand the
      applications of periodontal soft tissue grafts.

PMID- 29333766
TI  - [Relationship between different X-ray appearances and oral clinical
      manifestations of cemental dysplasia].
AB  - Cemental dysplasia is a non-neoplastic lesion and features different X-ray
      appearances that easily confuse dentists. This condition is often observed in
      conventional dental films or occasionally on panoramic radiographs. Cemental
      dysplasia is easily misdiagnosed as chronic periapical periodontitis,
      osteomyelitis, and tumor. In this paper, clinical mani-festations, imaging
      diagnosis, and the correlation between these variables are analyzed to achieve
      correct diagnosis.

PMID- 29333768
TI  - [Effects of geranylgeranyltransferase I gene silencing by RNA interference on the
      migration and invasion of tongue carcinoma].
AB  - OBJECTIVE: RNA interference was used to silence geranylgeranyltransferase
      I(GGTase-I) in vitro and to study the effect of GGTase-I on the migration and
      invasion of tongue squamous cancer cells. METHODS: Three small interfering RNAs
      (siRNA) were designed according to the GGTase-I sequence by Genebank and were
      transfected into tongue squamous cancer cells Cal-27 to knock down GGTase-I
      expression. The tested cells were divided into three groups, as follows: the RNA
      interfered groups (GGTase-I siRNA1, GGTase-I siRNA 2, GGTase-I siRNA 3), a
      negative control group (disrupted by random sequence NC-siRNA), and a blank
      control group. GGTase-I and RhoA gene expressions were examined by quantitative
      real-time polymerase chain reaction (qRT-PCR) and Western blot. The optimum
      interference group was screened by qRT-PCR and Western blot and was assigned as
      the experimental group. Matrix metalloproteinase (MMP)-2 and MMP-9 protein
      expressions were examined by Western blot. GTP-RhoA expression of protein was
      examined by GST-pull down. The migration and invasion abilities were analyzed by
      wound healing assay and Transwell motility assay. RESULTS: GGTase-I mRNA and
      protein expression in Cal-27 decreased significantly after transfection of GGTase
      I siRNA (P<0.05). No significant difference of RhoA gene expression was detected.
      MMP-2, MMP-9, and GTP-RhoA protein expressions decreased significantly (P<0.05).
      The migration and invasion abilities were inhibited (P<0.05). CONCLUSIONS: To
      inhibit GGTase-I expression, the migration and invasion abilities of tongue
      squamous cancer cells should also be inhibited. Further studies on GGTase-I may
      provide novel effective molecular targets for tongue squamous cancer cells.

PMID- 29333769
TI  - [Significance of the expression of proliferating cell nuclear antigen and P53 in
      the regeneration process of an atrophic parotid gland].
AB  - OBJECTIVE: This research aims to further explore the expression and significance
      of proliferating cell nuclear antigen (PCNA) and P53 in regenerating rat atrophy
      parotid gland from the gene and protein levels. METHODS: One hundred and two
      Wistar rats were randomly divided into experimental and control groups; the
      former group's duct was ligated and then released respectively in 7 (Group A) and
      14 days (Group B). Fresh parotid specimens were obtained at 0, 3, 5, 7, 10, 14,
      21, and 28 days after being released. Hematoxylin-eosin staining method was used
      to observe the morphological changes of the parotid gland. The significance of
      P53 and PCNA in two groups was resolved by real-time fluorescence quantitative
      polymerase china reaction and Western blot. RESULTS: Acinar cells aoptosis and
      duct cells proliferation occurred when the occlusion of the parotid duct was
      reversed on days 7 and 14. The expression of P53 was higher than that of PCNA,
      and they reached the peak at the third and fifth days after groups A and B
      regenerated, respectively. This finding was significantly different compared with
      the control (P<0.01). P53 and PCNA contents decreased gradually; acinar and duct
      gradually returned to normal morphology; PCNA and P53 contents gradually close to
      the normal control group. CONCLUSIONS: After ligating the parotid duct, P53 was
      highly expressed, and induced parotid gland atrophy. Mean-while, PCNA was highly
      expressed, which then decreased inducing gland recovery.

PMID- 29333770
TI  - [Construction of srtA-deletion mutant of Streptococcus mutans by an in-frame
      deletion system].
AB  - OBJECTIVE: To construct srtA-gene deletion mutant of Streptococcus mutans (S.
      mutans) UA159 with IFDC2 cassette through overlapping polymerase chain reaction
      (PCR) and allelic homologous recombination. METHODS: First, the upstream and
      downstream fragments surrounding the srtA and IFDC2 cassette were PCR amplified
      and ligated through overlapping PCR. The resulting amplicon was transformed into
      UA159, and positive transformants were selected on BHI plates containing
      erythromycin. Second, upstream and downstream fragments of srtA with overlap
      regions were generated by PCR and were overlapped to create upDelta-down
      amplicon. Then, the upDelta-down amplicon was transformed into the aforementioned
      positive transformants and selected on BHI plates containing p-Cl-Phe. RESULTS:
      The PCR analysis and DNA sequencing results indicated that the coding region of
      the srtA was completely deleted, and the upstream and downstream regions flanking
      the srtA were ligated seamlessly. CONCLUSIONS: The markerless srtA-deletion
      mutant of S. mutans was constructed successfully, which laid a foundation for
      further study of its biological function and influence on the biofilm formation
      of S. mutans.

PMID- 29333771
TI  - [Effect of hydrofluoric acid concentration on the surface morphology and bonding
      effectiveness of lithium disilicate glass ceramics to resin composites].
AB  - OBJECTIVE: This study aimed at determining the influence of hydrofluoric acid
      (HF) in varied concentrations on the surface morphology of lithium disilicate
      glass ceramics and bond durability between resin composites and post-treated
      lithium disilicate glass ceramics. METHODS: After being sintered, ground, and
      washed, 72 as-prepared specimens of lithium disilicate glass ceramics with
      dimensions of 11 mm*13 mm*2 mm were randomly divided into three groups. Each
      group was treated with acid solution [32% phosphoric acid (PA) or 4% or 9.5% HF]
      for 20 s. Then, four acidified specimens from each group were randomly selected.
      One of the specimens was used to observe the surface morphology using scanning
      electron microscopy, and the others were used to observe the surface roughness
      using a surface roughness meter (including Ra, Rz, and Rmax). After treatment
      with different acid solutions in each group, 20 samples were further treated with
      silane coupling agent/resin adhesive/resin cement (Monobond S/Multilink Primer
      A&B/Multilink N), followed by bonding to a composite resin column (FiltekTM Z350)
      with a diameter of 3 mm. A total of 20 specimens in each group were randomly
      divided into two subgroups, which were used for measuring the microshear bond
      strength, with one of them subjected to cool-thermal cycle for 20 000 times.
      RESULTS: The surface roughness (Ra, Rz, and Rmax) of lithium disilicate glass
      ceramics treated with 4% or 9.5% HF was significantly higher than that of the
      ceramic treated with PA (P<0.05). The lithium disilicate glass ceramics treated
      with 9.5% HF also demonstrated better surface roughness (Rz and Rmax) than that
      of the ceramics treated with 4% HF. Cool-thermal cycle treatment reduced the bond
      strength of lithium disilicate glass ceramics in all groups (P<0.05). After cool
      thermal cycle, the lithium disilicate glass ceramics treated with HF had higher
      bond strength than that of the ceramics treated with PA. The lithium disilicate
      glass ceramics treated with 4% HF had higher bond strength than that of the
      ceramics treated with 9.5% HF (P<0.05). During cool-thermal cycle, the lithium
      disilicate glass ceramics treated with 4% HF demonstrated higher reduction in
      bond strength than that of the samples treated with 9.5% HF (P<0.05).
      CONCLUSIONS: The concentration of HF significantly affected the surface
      morphology of lithium disilicate glass ceramics and the bond durability between
      resin composites and post-treated lithium disilicate glass ceramics. The bond
      strength between resin composites and post-treated lithium disilicate glass
      ceramic was more efficiently maintained by treatment with 9.5% HF.

PMID- 29333772
TI  - [Effect of different surface processes on the bond strength between zirconia
      framework and veneering ceramic].
AB  - OBJECTIVE: To compare the effect of different surface processes on bond strength
      and microscopic structure using a scanning electron microscope (SEM) and an
      energy distribution spectrum (EDS) at the bonding interface between zirconia
      framework and veneering ceramic. METHODS: WIELAND zirconia core material was cut
      into 33 rectangular specimens and fired on into rectangular specimens (10 mm*5
      mm*5 mm). The specimens were randomly divided into three groups (n=?11). The
      sandblasting group was sandblasted before firing. The sandblasting and liner
      coverage group was sandblasted before firing and then sintered with liner
      coverage after firing. The control group was not processed. All the veneering
      ceramics (5 mm*?5 mm*5 mm) were fired on into the zirconia substructure by slip
      casting technique. One bilayered specimen in each group was prepared for SEM and
      EDS to examine the bonding conditions. The other specimens were measured for
      shear force using an electronic universal dynamometer. The data obtained were
      analyzed by using the statistical software SPSS 17.0. RESULTS: The values of the
      shear bond strength test were (13.80+/-1.54) MPa for the control group, (18.06+/
      0.59) MPa for the sandblasting group, and (21.04+/-1.23) MPa for the sandblasting
      and liner coverage group. Significant differences existed among the three groups
      (P<0.01). CONCLUSIONS: Abrasion before firing significantly increases the shear
      bond strength of zirconia to veneering porcelain. The use of porcelain combined
      with liner increases the shear bond strength.

PMID- 29333773
TI  - [Influence of positional relationship between the long axis of the mandibular
      anterior teeth and the alveolar bone on the treatment design of dental implants].
AB  - OBJECTIVE: This study aimed at investigating and measuring the positional
      relationship between the long axis of the mandibular anterior teeth and the
      alveolar bone using cone beam computed tomography (CBCT) to provide reference
      data for implant treatment. METHODS: From the CBCT image database, 150 cases of
      radiographic data were selected according to the inclusion criteria and then were
      divided into six groups: males' mandibular central incisors, males' mandibular
      lateral incisors, males' mandibular canines, females' mandibular central
      incisors, females' mandibular lateral incisors, and females' mandibular canines.
      The angle (beta) formed by the long axis of the mandibular anterior teeth and the
      corresponding alveolar bone was measured and recorded. Based on the long axis of
      alveolar bone, if the teeth incline to the lingual side, the value of the angle
      (beta) was positive; otherwise, the value was negative. The resultant data were
      analyzed by SPSS 19.0. RESULTS: The beta of the mandibular central incisors
      presented a mean value of 4.77 degrees  (range: -8.17 degrees -16.10 degrees )
      for male subjects and 5.38 degrees  (range: -5.63 degrees -12.93 degrees ) for
      female subjects. The beta of the mandibular lateral incisors exhibited a mean
      value of 6.12 degrees  (range: -2.87 degrees -?17.57 degrees ) for male subjects
      and 5.81 degrees  (range: -7.70 degrees -15.70 degrees ) for female subjects.
      Finally, the beta of the mandibular canines presented a mean value of 5.01
      degrees  (range: -8.13 degrees -17.67 degrees ) for male subjects and 6.21
      degrees  (range: -7.70 degrees -17.87 degrees ) for female subjects. The
      percentages of the beta between -10 degrees  and 10 degrees  of males' mandibular
      incisors, mandibular lateral incisors, and mandibular canines were 87.34%,
      80.67%, and 88.00%, respectively and those of females were 90.67%, 82.66%, and
      82.66%, respectively. Whether male or female, the percentages of the beta between
      -10 degrees  and 10 degrees  of the mandibular anterior teeth were more than 80%.
      The beta that inclined to the lingual was not more than 20 degrees  and to the
      labial did not exceed 10 degrees . CONCLUSIONS: The long axis of the mandibular
      anterior teeth was almost consistent with the long axis of the alveolar bone.
      Therefore, the positional relationship could be referred to make reasonable
      implants treatment plan.

PMID- 29333774
TI  - [A cone beam computed tomography study on the anatomical position of accessory
      mandibular foramina in Jiangxi adults].
AB  - OBJECTIVE: This study used cone beam computed tomography (CBCT) to access the
      distribution and position of accessory mandibular foramina in the mandibular body
      of Jiangxi adults, and some safety rules of operation for clinics were provided.
      METHODS: Two hundred CBCT image subjects of Jiangxi adults were selected, which
      were divided into 4 groups by age with the same sex ratio. The number and
      position of accessory mandibular foramina in mandibular anterior teeth, premolars
      and molars region were described and the relationship between accessory
      mandibular foramina incidence and factors of age, gender and lateral were
      analyzed. RESULTS: A total of 1 123 accessory mandibular foramina were found,
      with a mean of 5.62+/-2.10 per person. The accessory mandibular foramina
      incidence decreased from the mesial region to the distal, and the lingual was
      higher than the buccal. There was no significant difference in the number of
      accessory mandibular foramina in male and female (P=0.195). However, the number
      of accessory mandibular foramina was negatively correlated with age (r(s)=
      0.301). Three highest frequency regions of accessory mandibular foramina were
      mandibular symphysis area (98.0%), lingual alveolar area of lower medial (88.0%)
      and lateral incisors and inferior area of lingual premolar (55.0%). CONCLUSIONS:
      Accessory mandibular foramina are widely presented in the body of everyone's
      mandible, addition attention should be paid to avoid the complications causing by
      the damage of canal contents in the clinics.

PMID- 29333775
TI  - [Effect of dexmedetomidine on emergence agitation after general anesthesia in
      children undergoing odontotherapy in day-surgery operating room].
AB  - OBJECTIVE: To study the effectiveness of dexmedetomidine used for general
      anesthesia maintenance in children undergoing odontotherapy in day-surgery
      operating room in reducing the incidence of emergence agitation (EA). METHODS:
      Eighty children undergoing odontotherapy and under general anesthesia in day
      surgery operating room were randomized into two groups, group A (n=40) and group
      B (n=40). Each patient in group A was administered with a bolus dose of
      dexmedetomidine (1.0 MUg.kg-1, saline diluted to 10 mL) pump-infused after
      intubation and a maintenance dose of 0.1-0.4 mL.(kg.h)-1 followed-up until 45 min
      before the end of operation. Each patient in group B was administered with a
      bolus dose of normal saline 10 mL pump-infused after intubation and maintenance
      dose of 0.1-0.4 mL.(kg.h)-1 followed-up until 45 min before the end of operation.
      Gender, age, weight, physical status according to the American Society of
      Anesthesiologists, perioperative heart rate (HR), mean arterial pressure (MAP),
      pulse oxygen saturation (SpO2), sufentanil dosage, duration of surgery, time of
      extubation, time of regaining consciousness, and time to reach modified Aldrete's
      score>=12 were recorded. Behavior in postanesthesia care unit was rated on the
      four-point agitation scale. RESULTS: Compared with group B, decreases were
      observed in HR and MAP at the beginning of operation, in 10 and 30 min, 1 and 2 h
      after the beginning of operation, and after extubation of group A (P<0.05).
      Sufentanil dosage and incidence of EA during recovery of group A were also lower
      than those of group B (P<0.05). Time to regain consciousness and time to reach
      modified Aldrete's score>=12 of group A were longer than those of group B
      (P<0.05). No statistical difference was observed between other indexes of the two
      groups. CONCLUSIONS: As an anesthetic used for general anesthesia maintenance in
      children undergoing odontotherapy in day-surgery operating room, dexmedetomidine
      results in low incidence of EA during recovery and more stable vital signs.

PMID- 29333776
TI  - [Clinical and microbiologic follow-up evaluations after non-surgical periodontal
      treatment with Nd: YAG laser and scaling and root planning].
AB  - OBJECTIVE: Our research aimed to detect the efficacy of non-surgical periodontal
      treatment with Nd: YAG laser and scaling and root planning (SRP) for chronic
      periodontitis. METHODS: We recruited chronic periodontitis patients who have more
      than four teeth with clinical pocket depth of 4-8 mm. These teeth were
      distributed in four different zones within the oral cavity. Moreover, the teeth
      were single root teeth and not adjacent to each other. The subordinated teeth
      were randomized into four groups, as follows: no treatment (C group), simple SRP
      (SRP group), Nd: YAG laser after SRP treatment (SRP+L group), and SRP after Nd:
      YAG laser treatment (L+SRP group). The four experimental observation points were
      as follows: before treatment (baseline) and 1 week, 1 month, and 3 months after
      treatment. We measured clinical indicators and collected subgingival deposits in
      the four time points to analyze changes of red complex in periodontitis. RESULTS:
      The clinical indicators were better in all treatment groups than in the control
      group. Comparison among treatment groups indicated that the value of bleeding on
      probing, periodontal probing depth, and clinical attachment loss showed no
      difference. However, the value of plaque index in SRP+L and L+SRP presented a
      significant reduction at 3 months after treatment. The percentages of
      Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola in all
      treatment groups decreased after clinical treatment, and differences were
      observed among the treatment groups at different time points. CONCLUSIONS: Non
      surgical periodontal treatment with SRP and Nd: YAG laser is not more effective
      than SRP monotherapy. The sequence of laser treatment and SRP has no significant
      effect on the treatment. However, SRP with Nd: YAG laser was beneficial for
      plaque control. Non-surgical periodontal treatment with Nd: YAG laser may be used
      as an alternative to reduce and control the proliferation of microorganisms in
      persistent periodontitis, but it still needs further verification.

PMID- 29333777
TI  - [Retrospective analysis of adverse drug reactions in stomatology hospital from
      2014 to 2016].
AB  - OBJECTIVE: This study aims to investigate the characteristics and general rules
      of adverse drug reactions (ADR) in a 3A-grade stomatology hospital for safe and
      rational drug use in clinical stomatology. METHODS: We retrospectively analyzed
      52 ADR cases (1?1.36, males?females) reported in the West China Hospital of
      Stomatology of Sichuan University from 2014 to 2016 in terms of gender and age
      distributions, drug categories, and clinical manifestations. RESULTS: Eight kinds
      of drugs and antibiotics were predominately used [24 cases, 46.15% (24/52)],
      followed by nutrition drugs and antitumor drugs. Cephalosporin was the leading
      antibiotic drug associated with ADR [20 cases, 83.33% (20/24)]. Intravenous
      infusion was the most common route of drug administration [49 cases, 94.23%
      (49/52)]. The most common manifestations of the ADR were damages of the skin and
      its appendages and lesions of the digestive and nervous systems. CONCLUSIONS:
      Strengthening the ADR monitoring system and further management should be
      implemented to alleviate ADR in stomatology hospitals.

PMID- 29333778
TI  - [Remineralization effect of casein phosphopeptide-amorphous calcium phosphate for
      enamel demineralization: a system review].
AB  - OBJECTIVE: This study  aims  to  assess  the  remineralization effect of casein
      phosphopeptide (CPP)-amorphous calcium phosphate (ACP) on enamel demineralization
      by  performing  system review of  randomized  controlled  trials (RCT)  involving
      the  treatment of enamel demineralization with  CPP-ACP. METHODS: The  study 
      was  developed  based  on  the ?Cochrane handbook  for  systematic  reviews of 
      interventions (Version 5.1.0) and included  the  following: search  strategy,
      selection  criteria, data  extraction, and  risk  of  bias  assessment. We 
      searched electronic  databases  such  as  PubMed, Embase, Cochrane Library, CNKI,
      Wanfang and VIP up  to  September  2016. RCT of  treating  enamel
      demineralization with  CPP-ACP were  included. Data  extraction  and  domain
      based  risk  of  bias  assessment  were independently  performed  by  two 
      reviewers. RESULTS: Twelve  RCTs  were  included.  Because of the difference of
      experimental design and evaluation standards, the quantitative analysis can not
      be carried out. CONCLUSIONS: There is no strong evidence that CPP-ACP is superior
      to conventional fluoride formulations in enamel remineralization. However, due 
      to the limitations of sample size, follow-up time and study design,  more high
      quality and large-sample RCT are needed to  further  verify  the evidence.

PMID- 29333779
TI  - [Decalcified freeze-dried bone allograft combined with rich platelet derivatives
      for the treatment of human periodontal intrabony defects: a Meta-analysis].
AB  - OBJECTIVE: This review aims to systematically evaluate the effect of decalcified
      freeze-dried bone allograft (DFDBA) combined with rich platelet derivatives on
      the treatment of human periodontal intrabony defects. METHODS: A search in
      PubMed, Web of Science, Embase, Cochrane Library, CNKI, and other electronic
      databases was conducted to identify randomized controlled trials (RCT) of the use
      of DFDBA combined with rich platelet derivatives in the treatment of human
      periodontal intrabony defects, performed before May 2016. The quality of the RCTs
      was assessed. RevMan 5.3 software was applied for Meta-analysis. RESULTS: A total
      of nine RCTs were included. A total of 194 patients and 303 defects were
      involved. Short-term (6 months) and long-term (12 to 18 months) groups were
      included. Meta-analysis results revealed that DFDBA combined with rich platelet
      derivatives was superior to DFDBA or rich platelet derivatives alone for probing
      depth reduction in the short-term [MD=0.75 mm, 95% confidence intervals (CI)
      (0.31 mm, 1.20 mm), P=0.001 0] and longterm groups [MD=0.87 mm, 95%CI (0.02 mm,
      1.72 mm), P=0.04], clinical attachment level gain in the short-term [MD=?0.65 mm,
      95%CI (0.08 mm, 1.22 mm), P=0.03] and long-term groups [MD=1.31 mm, 95%CI (0.60
      mm, 2.01 mm), P<0.000 3], gingival recession reduction in the long-term group
      [MD=-0.58 mm, 95%CI (-0.78 mm, -0.38mm), P<0.000 01], bone fill gain in the short
      term [MD=0.52 mm, 95%CI (0.03 mm, 1.00 mm), P=0.04] and long-term groups [MD=1.26
      mm, 95%CI (0.65 mm, 1.86 mm), P<0.000 1]. CONCLUSIONS: DFDBA combined with
      platelet rich derivatives is probably effective in the treatment of human
      periodontal intrabony defects. It is probably superior to DFDBA or platelet rich
      derivatives alone. Considering the limitation of the included studies, high
      quality and large-sample RCTs are required to evaluate the effect.

PMID- 29333780
TI  - [Progress in exogenous factors affecting the growth and remodeling of condylar
      process].
AB  - Condyle is a critical growth region of the mandible where mandible by
      endochondral ossification occurs. Condylar cartilage belongs to the secondary
      cartilage, which is not only affected by genetic factors but also by stress, drug
      intake, and other local factors. To promote the growth of the mandible, various
      exogenous and local factors were used to alter the biological environment of the
      condylar cartilage to stimulate endochondral ossification. This article reviews
      studies on the influence of exogenous factors on condylar growth and
      reconstruction. This literature review will provide a reference point for the
      treatment of patients with mandibular retraction.

PMID- 29333781
TI  - [Research progress on the relationship between triggering receptor expressed on
      myeloid cells 1 and 2 and malignant tumors].
AB  - Increasing scientific evidence supports the positive relationship between
      inflammation and cancer development. The immune response initiated by pattern
      recognition receptors is critical to triggering of tumor-associated inflammation.
      Triggering receptor expressed on myeloid cells (TREM) is an immunoglobulin of the
      super transmembrane glycoprotein family, which is mainly expressed on select
      groups of myeloid cells. The most important members of TREM comprise TREM-1 and
      TREM-2. Activation of TREM-1 and TREM-2 signaling is initiated upon binding of
      their ligands. Subsequently, cross-linking reactions of downstream effectors
      occur, resulting in inflammation regulation. Recently, the connection between
      TREM and malignant tumors has been widely noticed and studied. This review
      summarizes studies of association between TREM-1, TREM-2, and malignant tumors in
      the medical field to provide new ideas for study on the correlation between
      periodontitis and oral cavity cancer.

PMID- 29333782
TI  - [Research advances on the molecular mechanism of autophagy regulated by
      Porphyromonas gingivalis].
AB  - Autophagy is an intracellular conservative degradation pathway. This event has
      been considered as a key step in host defense against bacterial infection.
      However, Porphyromonas gingivalis, as one of the evidence-sufficient periodontal
      pathogens, can utilize self-induced autophagy to achieve persistent intracellular
      survival and proliferation, which enable this organism to escape from host immune
      surveillance. This review focuses on molecular mechanism of P. gingivalis
      internalization and autophagy to illuminate its pathogenesis and to further
      explore the relationship between P. gingivalis and systemic diseases.

PMID- 29333783
TI  - [Application of preoperative vascular localization techniques for perforator
      flaps].
AB  - With the development of microvascular technology, perforator flaps have gradually
      become a good alternative for reconstruction of tissue defects. However, the
      major limitations of perforator flaps include uncertainty in predicting
      anatomical location of perforators and high variability in perforator size and
      course, which require preoperative localization techniques. Recently, as one of
      the preoperative localization techniques, computed tomography angiography was
      used to determine the number, size, course, and exact emerging point of
      perforator flaps. Clinicians can reduce surgical complications and shorten
      operative time by using computed tomography angiography. However, only several
      studies reported clinical applications of computed tomography angiography. This
      article reviews characteristics, classification, and preoperative location
      techniques for perforator flaps and its problems.

PMID- 29333784
TI  - [Ancient human jaw osteomyelitis in Chinese Yangshao period: a case report].
AB  - This article reported jaw osteomyelitis in ancient human bone specimens, helping
      us to understand the emergence of ancient human jaw osteomyelitis and other oral
      health conditions.

PMID- 29333785
TI  - [Decoronation management of the replacement resorption after delayed replantation
      of avulsed teeth-case report with 4-year follow-up].
AB  - Replacement resorption is the most frequent complication after delayed
      replantation of avulsed teeth. The resorption can interfere with the development
      of the alveolar ridge and lead to tilt of the adjacent teeth in growing patients.
      However, there is no means of arresting or reversing the process. Recently
      decoronation is recommended by International Assocaition of Dental Traumatology
      as the optimal choice to manage it. This paper demonstrates the procedure and
      effectiveness of the decoronation by literature review and a case report with 4
      year follow-up.

PMID- 29333801
TI  - Efficacy of the Regent Suit-based rehabilitation on gait EMG patterns in
      hemiparetic subjects: a pilot study.
AB  - BACKGROUND: The recovery of the functional limb mobility of patients with
      cerebral damages can take great benefit of the role offered by proprioceptive
      rehabilitation. Recently have been developed a special Regent Suit (RS) for
      rehabilitative applications. Actually, there are preliminary studies which
      describes the effects of RS on gait recovery of stroke patients in acute stage,
      but none in chronic stage. Moreover, it is known that motor recovery does not
      always reflect improvements of the muscle activity and coactivity. AIM: To
      investigate the effects of proprioceptive stimulation induced by the Regent Suit
      (RS) on the EMG patterns during gait in post-stroke chronic patients. DESIGN:
      Randomized controlled trial. SETTING: S. Maugeri Foundation, Telese Terme (BN),
      Italy. POPULATION: Patients have been randomly assigned into two equal groups of
      20 patients: experimental group and traditional group. Further, a control group
      of 20 healthy subjects have been enrolled. METHODS: The traditional group
      attended a rehabilitation program composed by neuro-motor exercises without the
      RS, the experimental group performed the same rehabilitation program while
      wearing the RS. The NIH Stroke Scale (NIHSS), the Barthel Index (BI), the
      Functional Independent Measure (FIM) and the Berg Balance Scale (BBS) have been
      evaluated. EMG analysis has been performed considering the muscle activation
      timing over the gait of the soleus, tibialis anterior, semitendinosus and vastus
      lateralis muscles by decomposing the EMG signals into Gaussian pulses. Then, the
      symmetry of muscle activation and the muscle synergy patterns over the gait cycle
      have been assessed. RESULTS: The proprioceptive stimulation of the RS-based
      treatment induces higher and remarkable restoration of the normal muscle
      activation timing, also increasing the muscle symmetry and reducing the
      pathological muscle coactivation on both affected and non-affected sides.
      CONCLUSIONS: These results suggest confirm that a RS-based treatment is more
      effective than usual care in improving the EMG patterns during locomotion and
      daily living activities in chronic post-stroke subjects. CLINICAL REHABILITATION
      IMPACT: The proprioceptive rehabilitation Regent Suit based has an impact on
      motor function in stroke patients during gait.

PMID- 29333803
TI  - Pediatric journals of the Southern Cone. Similarities and differences.

PMID- 29333802
TI  - An upgraded model of teaching Physical and Rehabilitation Medicine: the vertical
      education approach of Split University, Croatia.

PMID- 29333804
TI  - Editors of biomedical journals and the disclosure of their own conflicts of
      interest.

PMID- 29333805
TI  - Bronchodilators in bronchiolitis: Yes or no?

PMID- 29333806
TI  - ASQ-3: Validation of the Ages and Stages Questionnaire for the detection of
      neurodevelopmental disorders in Argentine children.
AB  - INTRODUCTION: The systematic assessment of child development in the first years
      of life is an essential component of pediatric health checkups. The Ages and
      Stages Questionnaire, third edition (ASQ-3) is the most validated scale, and has
      been recommended by the UNICEF to verify if children have a normal neurological
      development. It is a monitoring instrument to assess the main developmental
      areas, including communication, gross motor, fine motor, personal-social, and
      problem solving skills, and to compare the local population to the international
      development standards. OBJECTIVE: To validate the ASQ-3 in a pediatric population
      group. METHODS: Children aged 1-66 months were assessed at a public hospital by
      pediatricians, psychologists, and educational psychologists. The SSPS software
      package was used to determine population scales. RESULTS: In 630 children, who
      had a homogeneous sex distribution, an 88% sensibility and a 94% specificity were
      determined, with a positive predictive value of 88% and a negative predictive
      value of 96%, compared to the National Screening Test (Prueba Nacional de
      Pesquisa, PRUNAPE) and the cut-off scores for each age group. CONCLUSION: The ASQ
      3 established that 19.5% of children were at risk of experiencing
      neurodevelopmental disorders. The ASQ-3 met psychometric properties compared to
      the PRUNAPE, which is the gold standard for the targeted and systematic
      assessment of developmental milestones during health checkups in a rapid, simple
      and cost-effective manner, so it was considered useful to monitor child
      neurological development.

PMID- 29333807
TI  - Contribution of diet to lead exposure among children aged 1 to 7 years in La
      Plata, Buenos Aires.
AB  - INTRODUCTION: Lead is a toxic metal which, even at low blood levels, can alter
      normal neurodevelopment in children, so no blood lead level is acceptable. Lead
      absorption from diet accounts for the highest contribution to blood lead levels
      in the population who is not exposed to contaminated environments or because of
      their occupation. The objective of this study was to determine the contribution
      of diet to lead exposure among children aged 1 to 7 years who attended Hospital
      de Ninos de La Plata for health check-ups. POPULATION AND METHODS: The study was
      conducted between June 2015 and May 2016. A questionnaire on the frequency of
      food intake was administered to 91 children whose average age +/- standard
      deviation was 3.0 +/- 1.7 years, and foods included in the analysis were selected
      based on this questionnaire. Selected foods were purchased from different
      regional stores. Composite samples were made up of different food groups. Lead
      levels corresponding to each food group were determined and, finally, the daily
      intake of lead was estimated for the studied population. RESULTS: The daily
      intake of lead was 138 ug/day. The food groups with the higher intake rates were
      processed meat products (15.4%), bakery products (14.8%), milk (12.5%), and meat
      (11.7%). CONCLUSIONS: Children aged 1 to 7 years attending a public hospital in
      La Plata have a lead burden from dietary intake of 138 ug/day.

PMID- 29333808
TI  - The perspective of primary health care pediatricians regarding childhood anemia
      and iron supplementation.
AB  - INTRODUCTION: Iron deficiency anemia is common in low- and middle-income
      countries. According to the evidence, the impact of ferrous sulfate
      supplementation in the pediatric population is low. Our objective was to analyze
      the perspective of pediatricians regarding anemia and iron supplementation.
      POPULATION AND METHODS: Qualitative, exploratory study. Semi-structured
      interviews were conducted with primary health care pediatricians from Rosario.
      Three core inquiry concepts were included: importance of this problem, clinical
      practice, and representations about iron supplementation. The analysis consisted
      in the systematization of the information collected by transcribing the recorded
      interviews and notes. RESULTS: A total of 32 interviews were conducted. All
      interviewees considered anemia was a relevant problem. At present, anemia is
      associated with a poor-quality diet. Based on the findings, pediatric practice
      follows national standards. There is consensus that low adherence is a barrier
      for the clinical management of iron deficiency anemia. Pediatricians described
      concepts that are potentially beneficial for the local setting, including
      workshops on anemia and free provision of more flavorful iron supplements.
      CONCLUSIONS: Iron deficiency anemia was considered a severe problem. In the
      primary health care setting, outstanding interventions included workshops and
      access to more flavorful iron supplements.

PMID- 29333809
TI  - Assessment of orofacial pain management in a pediatric emergency department and
      at home after discharge.
AB  - INTRODUCTION: An inadequate pain management is common in the emergency
      department. Our objective was to analyze pain management among children with an
      orofacial infection or trauma in the emergency department and to assess
      compliance and satisfaction with analgesia prescribed at discharge. POPULATION
      AND METHODS: Cross-sectional, observational and analytical study in children
      attending the emergency department for an orofacial infection or trauma over 2
      months. Pain management in the emergency department, analgesia prescribed at home
      and, following a call to parents, treatment provided and its adequacy to control
      pain were registered. RESULTS: In total, 252patients (mean age: 4.5 years, SD:
      3.89) were included. Pain assessment was recorded at the triage for 8.7%, and in
      the medical report, for 3.6%. Analgesia was administered to 41.3% in the
      emergency room. At discharge, no analgesia was prescribed to 13.9%; scheduled
      analgesia, to 25.4%; and as needed, to 60.3%. Pediatricians prescribed scheduled
      analgesia more frequently than surgeons (34.4% versus 16.5%, p < 0.01). At home,
      no analgesia was administered to 39.3%; scheduled analgesia, to 36.1%; and as
      needed, to 23%. There is little correlation between prescription at discharge and
      at home (Kappa: 0.178). Analgesia was considered adequate in 84% of cases, and
      was more frequent in trauma injuries than in infections (85.7% versus 14.3%, p <
      0.01). CONCLUSIONS: Pain assessment and management was scarce in the emergency
      department. The most common prescription was as needed, contrary to what is
      recommended in the guidelines. Analgesic control worked better for trauma
      injuries than for infections.

PMID- 29333810
TI  - The value of acute phase reactants and LightCycler(r) SeptiFast test in the
      diagnosis of bacterial and viral infections in pediatric patients.
AB  - INTRODUCTION: This study was performed to investigate the value of acute phase
      reactants and LightCycler(r) SeptiFast test to differentiate bacterial and viral
      infections. POPULATION AND METHODS: Children with fever were enrolled to this
      prospective study. Peripheral white blood cell (WBC), C-reactive protein (CRP)
      and procalcitonin (PCT) were studied from all patients on day 1, 3 and 7. Blood
      culture and chest X-ray were also obtained on day 1. Blood samples for
      LightCycler(r) SeptiFast test were obtained in all patients to use them if there
      was uncertain diagnosis between bacterial or viral infection. The patients were
      divided into two groups as bacterial and viral infection. RESULTS: A total of 94
      children with fever were enrolled. The mean value of fever was significantly
      higher in bacterial group than viral group (p <0.001). In bacterial infection
      group, 34 (72.3%) patients had negative blood culture. Of those, 12 (35.2%) had
      positive SeptiFast test. There were no positive blood culture in patients with
      viral infection group and all of them had negative SeptiFast test. The mean
      levels of CRP on the first day of admission were significantly higher in
      bacterial group than viral group (p <0.001). CRP and PCT levels of day 3 and 7
      were significantly higher in bacterial group (p <0.001). The sensitivity and
      specificity levels of WBC, CRP and PCT were 63.8%, 44.7%, 74.5% and 78.7% ,68.1%
      and 100%, respectively. CONCLUSIONS: We found that acute phase reactants,
      especially PCT, and LightCycler(r) SeptiFast test may help to differentiate
      bacterial and viral infections.

PMID- 29333811
TI  - Neonatal mortality and associated factors in newborn infants admitted to a
      Neonatal Care Unit.
AB  - INTRODUCTION: The increasing survival rate of preterm infants has altered the
      epidemiology of neonatal diseases; however, neonatal mortality is still the main
      component of child mortality. The objective of this study was to evaluate
      neonatal mortality and associated factors in newborn infants admitted to a
      neonatal care unit. MATERIAL AND METHODS: Prospective cohort study conducted
      between January 2016 and January 2017 at Hospital Civil de Guadalajara "Dr. Juan
      I. Menchaca." The incidence of deaths and associated conditions was evaluated
      using a multivariate logistic regression analysis. RESULTS: A total of 9366 live
      births were registered; 15% (n: 1410) of these were admitted to the neonatal care
      unit. The mortality rate was 125.5 per 1000 hospitalized newborn infants (95%
      confidence interval [CI]: 109-144); the main reasons for admission were
      congenital malformations or genetic disorders (28.2%), infections (24.9%), and
      respiratory distress (20.9%). The conditions associated with death were
      gestational age < 37 weeks (OR: 2.41, 95% CI: 1.49-3.93), birth weight < 1500
      grams (OR: 6.30, 95% CI: 4.15-9.55), moderate/severe respiratory distress at 10
      minutes (OR: 1.89, 95% CI: 1.24-2.86), Apgar score < 7 at 5 minutes (OR: 9.40,
      95% CI: 5.76-15.31), congenital malformations (OR: 5.52, 95% CI: 3.12-9.78), and
      less than 5 antenatal care visits (OR: 1.51, 95% CI: 1.09-2.08). CONCLUSIONS:
      Preterm birth, low birth weight, respiratory distress, Apgar score < 7,
      congenital malformations, and a history of < 5 antenatal care visits were
      associated with a higher risk for death.

PMID- 29333812
TI  - Markers of inflammation and tolerance development in allergic proctocolitis.
AB  - BACKGROUND: Today, as a result of an increase in the frequency of food protein
      induced allergic proctocolitis (FPIAP), there is a need for studies not only to
      enlighten the pathophysiology of the disease but also to determine simple, non
      invasive markers in both diagnosis, and evaluation of the development of
      tolerance. No study has been found in the literature about the place of
      neutrophil/lymphocyte ratio (NLR) and mean platelet volume (MPV), which are easy
      to calculate and non-invasive markers. OBJECTIVES: The purpose is to determine
      the relation between NLR and MPV with the diagnosis and development of tolerance
      in children with FPIAP. METHODS: In this retrospective cross-sectional study,
      clinical, demographic symptoms and laboratory findings of patients, monitored
      with FPIAP diagnosis in allergy and gastroenterology clinics, were acquired from
      the patient record system. Hemogram values at the time of diagnosis were compared
      with the values of healthy children of the same age and gender. RESULTS: Among 59
      patients diagnosed with FPIAP, males constitute 47.4% and females constitute
      52.6%. MPV and platelet crit (PCT) values were significantly high when compared
      to the control group (n: 67) in FPIAP cases (p < 0.001). Also, MPV and PCT values
      were significantly high in non-tolerance developing cases when compared to
      developing ones (p= 0.01). CONCLUSIONS: Contrary to NLR, MPV and PCT values have
      been considered to be good markers in predicting prognosis in cases with FPIAP
      since they are quick, cost effective and easy to calculate.

PMID- 29333813
TI  - Body composition and energy expenditure in a population of children and
      adolescents with myelomeningocele.
AB  - INTRODUCTION: Myelomeningocele is a congenital defect that occurs when the neural
      tube fails to close completely. It causes body composition alterations and a high
      prevalence of obesity. It is difficult to detect the most adequate indicator for
      a nutritional diagnosis due to the impossibility of recording accurate
      anthropometric measurements. OBJECTIVE: To describe body composition, resting
      energy expenditure and metabolic disorders in a population of patients with
      myelomeningocele managed at "Hospital Garrahan" by comparing obese patients with
      myelomeningocele and a control population with multifactorial obesity. POPULATION
      AND METHODS: An anthropometry, an impedance analysis, skinfold equations, arm
      circumference equations, indirect calorimetry, and biochemical determinations
      were done to all patients with myelomeningocele between June 2013 and April 2014,
      once the informed consent had been signed. RESULTS: 131 patients aged 0.7-18.6
      years were assessed; they were classified according to their body mass index Z
      score into low weight (15%), normal weight (42%), overweight (12%), and obese
      (31%). A high correlation (r: 20.74) was observed between the fat mass % measured
      by impedance analysis versus that estimated using skinfolds. Patients with a high
      fat mass % had a higher body mass index Z-score than those with a normal fat mass
      % (1.07 versus -0.27, p: 0.0001) although both values were within normal
      parameters. A lower resting energy expenditure was observed among obese patients
      with myelomeningocele than predicted and in comparison with multifactorial obese
      controls. CONCLUSIONS: A high percentage of overweight/obesity was found in the
      population with myelomeningocele. Skinfold equations would be more adequate to
      detect obesity. Obese patients with myelomeningocele had a lower resting energy
      expenditure than predicted and in comparison with controls. Energy indication
      should be customized.

PMID- 29333814
TI  - Morbidity in congenital heart surgery in a public hospital in Argentina.
AB  - OBJECTIVE: To describe the complications associated with heart surgery, compare
      them to a reference population, and identify mortality risk factors. PATIENTS AND
      METHODS: Retrospective and descriptive study. All patients who underwent surgery
      at Hospital Garrahan in the 2013-2015 period were included. Age, weight,
      procedure, mechanical ventilation, length of stay in days, morbidity, and course
      were recorded. Renal failure requiring dialysis, neurological deficit, permanent
      pacemaker, circulatory support, phrenic nerve or vocal cord palsy, reoperation,
      wound infection, chylothorax, and tracheotomy were considered morbidities. A
      descriptive, statistical analysis by risk category was done using the Society of
      Thoracic Surgeons (STS) morbidity score. RESULTS: 1536 patients, median age: 12
      months (interquartile range [IQR] 25-75: 3-60), weight: 8 kg (IQR 25-75: 4.4 to
      17.5), mortality: 5%. A total of 361 events were recorded in 183 patients. An
      unplanned reoperation was the most common event (7.2%); the rest occurred in < 3%
      of patients. Compared to patients without complications, patients who had events
      required more days on mechanical ventilation: 9.95 (IQR 25-75: 7.6512.24) versus
      1.8 (IQR 2575: 1.46-2.14), p< 0.00001; a longer length of stay: 28.8 (IQR 25-75:
      25.1-32.5) versus 8.5 (IQR 25-75: 7.9-9.2), p< 0.0001; and had a higher
      mortality: 19.6% versus 3.1% (RR: 4.58, 95% CI: 3.4 to 6.0), p< 0.0001.
      Circulatory support and renal failure were associated with a higher mortality.
      CONCLUSIONS: An unplanned reoperation was the most common event. Patients with
      complications required more days on mechanical ventilation and a longer length of
      stay and had a higher mortality. Circulatory support and renal failure were
      associated with a higher mortality.

PMID- 29333815
TI  - Prevalence of vitamin K deficiency and associated factors in non-supplemented
      cystic fibrosis patients.
AB  - INTRODUCTION: Vitamin K deficiency is highly prevalent in cystic fibrosis (CF)
      patients despite supplementation. Moreover, no reliable risk factors for its
      occurrence are known. The aim was to assess the prevalence of vitamin K
      deficiency and associated factors in non-supplemented CF patients. METHODS:
      Prothrombin concentration induced by vitamin K absence (PIVKA-II) and the
      undercarboxylated osteocalcin percentage (u-OC) were determined. In all patients
      clinical status was assessed and its relation to vitamin K deficiency determined.
      The following tests were used for statistical analysis: Mann-Whitney test, ANOVA
      test or the Kruskal Wallis test, the chi-squared test or the Fisher-Freeman
      Halton test, and multiple linear and multiple forward stepwise logistic
      regression analysis. RESULTS: The study group comprised 79 CF patients aged 0.4
      25.3 years. PIVKA-II and u-OC were abnormal in 56 (70.9%) and 45 (57.0%)
      patients. Patients with elevated PIVKA-II were significantly older (p= 0.0184)
      and had lower Z-score values for body weight (p= 0.0297) than those with normal
      concentrations. Patients with normal or pathological u-OC percentage did not
      differ. Abnormal PIVKA-II and u-OC were reported more frequently in subjects with
      two severe CFTR mutations and with worse/poor nutritional status. Multiple linear
      and forward stepwise regression analyses did not reveal strong predictive factors
      of vitamin K deficiency. CONCLUSION: Vitamin K deficiency is highly prevalent in
      the natural course of cystic fibrosis. There are no reliable clinical
      determinants of its occurrence.

PMID- 29333816
TI  - National Health Care Network for children with oral clefts: organization,
      functioning, and preliminary outcomes.
AB  - INTRODUCTION: Oral clefts are major congenital anomalies that may affect the lip
      and/or palate, and that may also involve the nose and nostrils. In Argentina,
      their prevalence is approximately 15 per 10 000 births. In 2015, the Ministry of
      Health of Argentina created a national health care network for children with oral
      clefts in Argentina through the joint work with the National Registry of
      Congenital Anomalies (Red Nacional de Anomalias Congenitas, RENAC) (coordinating
      center for the national network) and the SUMAR Program. The objective of this
      study was to describe the health care network and its preliminary outcomes.
      POPULATION AND METHODS: A total of 61 centers that provided a comprehensive
      treatment for oral clefts or in collaboration with other centers were identified
      and accredited. Maternity centers were connected with treating centers grouped in
      health care network nodes. RESULTS: In the period between March 2015 and February
      2016, 550 newborn infants who were exclusively covered by the public health care
      system were identified. Among these, 18% had a cleft lip; 62%, cleft lip and
      palate; and 20%, cleft palate only; 75% were isolated cases and 25%, in
      association with other congenital anomalies. CONCLUSION: Approximately 70% of
      children were assessed by a certified treating institution and are receiving
      treatment. The network seeks to improve data systematization, include the largest
      number of centers possible, strengthen interdisciplinary team work, and promote
      high-quality standards for treatments.

PMID- 29333817
TI  - Anthropometric and biochemical assessment of nutritional status and dietary
      intake in school children aged 6-14 years, Province of Buenos Aires, Argentina.
AB  - INTRODUCTION: Childhood obesity is a global epidemic. School age and adolescence
      are critical stages for the implementation of eating and lifestyle habits.
      OBJECTIVE: To assess anthropometric and biochemical assessment of nutritional
      status and dietary intake in children, their relationship with socioeconomic
      factors and georeferencing. METHODS: Cross-sectional study in schoolchildren aged
      6-14 years from the District of General Pueyrredon, during August-November 2013.
      Dietary intake was assessed using a 24-hour dietary recall interview, and
      georeferencing was done using the gvSIG software. RESULTS: A total of 1296
      children were included for anthropometric and socioeconomic assessment. A sub
      sample included 362 children for intake and biochemical parameters. Overweight
      was observed in42.97% (95% confidence interval [CI]: 40.3-45.7) and obesity, in
      18.5% (95% CI: 16.320.5). Breakfast was related to a lower risk for overweight
      (OR: 0.7, 95% CI: 0.5-0.9) and obesity (OR: 0.7, 95% CI: 0.5-0.9). Attending high
      school was related to a lower prevalence of weight excess (OR: 0.45, 95% CI: 0.3
      0.7); male sex posed a higher risk for obesity (OR: 1.7, 95% CI: 1.3-2.3). Also,
      4.44% of participants had anemia; 19.6%, hypercholesterolemia; and 21.3%,
      hypertriglyceridemia. Lipid and saturated fat intake was high, whereas dietary
      cholesterol and fiber intake was low. Geographic distribution was homogeneous.
      CONCLUSIONS: The prevalence of overweight was high. The risk for obesity was
      higher among boys; breakfast appeared as a protective factor against
      overweight/obesity. A low-fiber and high-fat intake, and high blood cholesterol
      and triglyceride levels reveal that overnutrition is a prevalent public health
      problem.

PMID- 29333819
TI  - Hashimoto's disease in a cohort of 29 children and adolescents. Epidemiology,
      clinical course, and comorbidities in the short and long term.
AB  - Hashimoto's thyroiditis is the most common cause of goiter and hypothyroidism
      among children and adolescents. Its clinical manifestations and course vary. The
      objective of this study was to review the clinical and evolutionary
      characteristics of Hashimoto's disease in the pediatric population. Clinical,
      analytical, ultrasound, epidemiological, and evolutionary data of patients with
      autoimmune thyroiditis seen at Hospital Universitario San Juan de Alicante
      between January 2010 and January 2016 were analyzed. A total of 29 patients were
      included in the study. A higher prevalence of girls was observed, at a 2:1 ratio.
      The main reason for consultation was the accidental detection of high thyroid
      stimulating hormone levels or positive anti-thyroid antibodies in a lab test done
      for other reason. In the initial analysis, 53.3% of patients had subclinical
      hypothyroidism and only 10% of them had frank hypothyroidism. Two patients
      developed thyroid cancer.

PMID- 29333818
TI  - Community-acquired methicillin-resistant Staphylococcus aureus infections:
      hospitalization and case fatality risk in 10 pediatric facilities in Argentina.
AB  - INTRODUCTION: Community-acquired methicillin-resistant Staphylococcus aureus (CA
      MRSA) infections are prevalent both in Argentina and worldwide, and they may have
      a severe clinical course. OBJECTIVES: To estimate the hospitalization rate and
      case fatality risk factors of CA-MRSA infection. METHODS: Cross-sectional,
      analytical study. All patients < 15 years old with community-acquired
      Staphylococcus aureus (CA-SA) infections admitted to 10 pediatric facilities
      between January 2012 and December 2014 were included. RESULTS: Out of 1141
      patients with CA-SA, 904 (79.2%) had CA-MRSA. The rate of hospitalization of CA
      MRSA cases (per 10 000 discharges) among patients < 5 years old was 27.6 in 2012,
      35.2 in 2013, and 42.7 in 2014 (p = 0.0002). The 2-4-year-old group was the most
      affected one: 32.2, 49.4, and 54.4, respectively (p = 0.0057). The clinical
      presentations included skin and soft tissue infections: 66.2%, pneumonia: 11.5%,
      sepsis/bacteremia: 8.5%, osteomyelitis: 5.5%, arthritis: 5.2%, psoas abscess:
      1.0%, pericarditis/endocarditis: 0.8%, meningitis: 0.6%, and other: 0.7%. In
      terms of antibiotic resistance, 11.1% had resistance to erythromycin; 8.4%, to
      gentamicin; and 0.6%, to trimethoprim-sulfamethoxazole. All strains were
      susceptible to vancomycin. The case fatality rate was 2.2% and associated risk
      factors were (odds ratio [95% confidence interval]) age > 8 years (2.78, 1.05
      7.37), pneumonia (6.37, 2.3717.09), meningitis (19.53, 2.40-127.87), and
      sepsis/bacteremia (39.65, 11.94-145.55). CONCLUSIONS: The rate of CA-MRSA
      infection was high; the rate of hospitalization increased in the 2013-2014
      period; the 2-4-year-old group was the most affected one. A higher case fatality
      risk was observed among patients > 8 years old and those with the clinical
      presentations of pneumonia, meningitis, and sepsis.

PMID- 29333820
TI  - Osteomyelitis in burn children: Ten years of experience.
AB  - INTRODUCTION: Osteomyelitis is uncommon among burn patients. OBJECTIVE: To
      describe the clinical, microbiological, and evolutionary characteristics of burn
      children with osteomyelitis hospitalized in a tertiary care facility. METHODS:
      Retrospective and descriptive study conducted between January 2007 and January
      2017. RESULTS: Out of 600 burn children, 12 developed osteomyelitis (incidence:
      2%). Eleven patients had a burn caused by direct fire. Patients' median age was
      42.5 months (interquartile range [IQR]: 27-118 months), and their median burned
      surface area was 33.5% (IQR: 18.5-58%). Osteomyelitis was diagnosed at a median
      period of 30 days following the burn injury. The most common locations were the
      upper limbs and the cranial vault. Fever was the most frequent clinical
      manifestation. The most common microorganisms isolated in bone tissue were fungi
      in 9 patients. All showed compatible anatomopathological findings. The treatment
      lasted a median of 44.5 days (IQR: 34.5-65.5 days). Six patients had motor
      sequelae and 1 died. CONCLUSION: Fungal osteomyelitis was the most commonly
      observed etiology. Half of patients had functional sequelae and only 1 patient
      died.

PMID- 29333822
TI  - Labial adhesions: Experience in a children's hospital.
AB  - Labial adhesions are defined as the complete or partial fusion of the pudendal
      cleft due to the agglutination of the labia minora in the midline. They most
      commonly occur between 3 months and 6 years of life. Between January 1st, 2002
      and December 31st, 2015, 425 girls diagnosed with labial adhesions and seen at
      the Unit of Pediatric and Adolescent Gynecology of Hospital de Ninos de La Plata,
      Argentina, were analyzed. Their average age was 2.7 years (standard deviation:
      2.6 years). The most common presentation of labial adhesions was that involving
      more than 75% of the total length of the labia (p < 0.0000001). A total of 84.2%
      of patients showed no symptoms and 4% had urinary symptoms. Also, 68.4% of the
      girls who had a history of urinary tract infection had labial adhesions with a
      length of involvement of > 75%. Finally, 90.6% of cases resolved with topical
      estrogens; and 2.1% had adverse events.

PMID- 29333821
TI  - Opioid treatment for mixed pain in pediatric patients assisted by the Palliative
      Care team. Five years of experience.
AB  - Pain is defined as an unpleasant sensory and emotional experience associated with
      actual or potential tissue damage. Depending on its pathophysiological mechanism,
      it may be classified into nociceptive, neuropathic, and mixed pain. If pain is
      moderate to severe, a strong opioid should be administered and, when this is the
      case, morphine is the drug of choice. If morphine is ineffective or causes
      intolerable adverse effects, opioid rotation is recommended. Our objective was to
      describe the drug management for mixed pain used in patients assisted by the
      Palliative Care team of Hospital General de Ninos Pedro de Elizalde between
      August 2011 and September 2015. A total of 72 patients were included. Their mean
      age was 10.1 years, and the most common underlying disease was cancer. The
      initial opioid was morphine in 57 cases; 48 patients received adjuvant drugs.
      Opioid rotation was indicated in half of cases, and the most common switch was
      from morphine to methadone.

PMID- 29333824
TI  - Eosinophilic esophagitis and esophageal atresia: coincidence or causality?
AB  - Eosinophilic esophagitis is an immune-mediated chronic disease of the esophagus
      characterized by symptoms related to esophageal dysfunction and tissue
      eosinophilia. In the endoscopy, the esophageal mucosa may appear normal or show
      exudates, rings, edema, furrows, and strictures. Its management is based on
      elimination diet, topical corticosteroids and/or esophageal dilation. Atresia is
      the most common congenital alteration of the esophagus; it requires surgical
      repair and poses potential complications, such as gastroesophageal reflux,
      strictures, and esophageal dysmotility. Up to 2015, 48 cases of eosinophilic
      esophagitis and esophageal atresia were reported, with dysmotility, reflux, and
      long-term acid suppression involvement. Prevalent clinical signs include
      dysphagia, difficulty eating, and reflux symptoms, so an
      esophagogastroduodenoscopy with biopsy is recommended to rule out associated
      eosinophilic esophagitis in patients with esophageal atresia and persistent
      symptoms before performing an esophageal dilation and/or anti-reflux surgery. If
      eosinophilic esophagitis is confirmed, it should be managed with the
      corresponding drugs, and the subsequent therapeutic approach will depend on its
      clinical course.

PMID- 29333823
TI  - Brain death and organ donation in Argentine pediatric intensive care units. A
      multicenter study.
AB  - Brain death (BD) is a condition determined by the complete and irreversible
      absence of brain functions. Maintenance of vital functions creates an opportunity
      for organ donation. A retrospective study was carried out in 7 pediatric
      intensive care units of Argentina (from 1/1/2013 to 9/30/2016) to determine the
      incidence of clinical and certified BD, and the proportion of effective
      transplantations. Among deceased patients, 19.14% (147/768) met the clinical
      requirements for BD, and the main cause of BD was multiple trauma. BD was
      certified in 13.4% of deceased patients (103); an electroencephalogram and an
      apnea test were the most commonly used ancillary methods. Organ maintenance time
      was 24 hours. A total of 87 families were approached for donation; 59 were
      rejected (they were not suitable or refused). Effective donors accounted for 25%
      (26/103) of patients with certified BD and 72 patients received solid organs.

PMID- 29333825
TI  - 6 minutes.
AB  - At present, there is a trend towards reducing the duration of office visits. In
      some regions of Spain, it has been set at 6 minutes per patient. This impacts on
      several levels: literally, many times it is impossible to complete the medical
      act; at an emotional level, because there is little possibility to establish an
      adequate doctor-patient relationship; and symbolically, for considering that the
      main aspects of humane health care are expendable. This takes place in a society
      that tends to see health care as a merchandise subject to market rules that gives
      priority to the immediate over the important. Patients, physicians, and managing
      authorities are participants of this change which negatively affects current
      medical practice. The increase in unnecessary additional testing, avoidable
      treatments, the costs of iatrogenesis, a lower treatment adherence, and
      unnecessary reconsultations are proven consequences. In the field of pediatrics,
      this increases the risk of losing screening opportunities in critical areas.

PMID- 29333826
TI  - Vitamin D deficiency in pediatric clinical practice.
AB  - INTRODUCTION: Vitamin D research suggests it has a role in disorders other than
      bone metabolism. OBJECTIVE: To update the information on vitamin D deficiency
      (VDD) in pediatric clinical disorders. METHODS: Search in virtual libraries,
      giving priority to clinical and longitudinal studies and meta-analyses on VDD in
      the pediatric age group published in the past 20 years. The terms "vitamin D
      deficiency", "children and adolescents" (both in Spanish and English) were used
      as search descriptors. RESULTS: In the pediatric population, VDD is associated
      with different clinical diseases, such as bone alterations, insulin resistance,
      metabolic syndrome, respiratory tract infections, asthma, and autoimmune
      diseases. Besides, it is associated with prematurity, obesity, malabsorption, use
      of anticonvulsant agents, and lifestyle characteristics, such as clothing,
      extreme latitudes, low consumption, and little sun exposure. CONCLUSIONS:
      According to the evidence, VDD is highly prevalent in several disorders and
      diseases in the pediatric age group. The recommendation is to prevent VDD in risk
      conditions and to maintain 25(OH)D serum levels > 75 nmol/L.

PMID- 29333827
TI  - Rectus sheath hematoma in a macrosomie neonate following difficult delivery. Case
      report.
AB  - Macrosomia is a risk factor for birth injuries and is associated with neonatal
      morbidity and mortality. Cephalohematoma and clavicular fracture are the most
      frequent birth injuries. Intraabdominal injuries are uncommon birth injuries.
      Rectus sheath hematoma (RSH) is an accumulation of blood in the sheath of rectus
      abdominis muscle. It is associated with trauma, operations and anticoagulant
      therapy, especially in adults and elders. We present a macrosomic male neonate
      with difficult vaginal delivery, who had in the physical examination periumblical
      ecchymose of 1x1 cm and a parietal cephalohametoma of 1x1 cm. The abdominal
      ultrasonogram and the computed tomography scan of the abdomen showed a 7x4x2 cm
      right rectus sheath hematoma.

PMID- 29333828
TI  - [Congenital Horner syndrome. Case report].
AB  - Horner syndrome is characterized by the following triad of clinical signs:
      miosis, ptosis and facial anhidrosis. In addition, iris heterochromia,
      conjunctival injection, facial erythema, congestive nasal mucosa and apparent
      enophthalmos secondary to the reduction of the palpebral fissure can appear. It
      is caused by an interruption of the sympathetic pathway that extends from the
      hypothalamus to the orbit. Because there is no decussation, the signs are
      homolateral to the lesion. Traditionally, it is classified as congenital and
      acquired. Occasionally, it is associated with neoplasias such as neuroblastoma.
      It remains controversial what imaging studies should be requested as a
      protocolized workup of this neurological syndrome in a patient. We report the
      case of a 45-day-old infant with congenital Horner syndrome.

PMID- 29333829
TI  - [Galactosialidosis: a new "de novo" mutation in CTSA gene in a patient with late
      infantile galactosialidosis].
AB  - Galactosialidosis (OMIM #256540) is an autosomal recessive lysosomal storage
      disorder caused by mutations in the CTSA gene, which encodes the protective
      protein cathepsin A. The loss of function of this protein causes a secondarily
      deficiency of beta-galactosidase and N-acetyl-a-neuraminidase enzymes activities.
      We describe the clinical, biochemical and molecular analysis of a case report
      with a phenotype compatible with the late infantile form. The biochemical
      analysis reveled deficiencies of beta-galactosidase and neuraminidase activities
      in dried blood spot and fibroblasts and the molecular study showed two missense
      mutations in the CTSA gene: a previously reported mutation, p.Arg441Cys
      (c.1321C>T), and a novel mutation, p.His475Pro (c.1424 A>C), located in exons 14
      and 15, respectively.

PMID- 29333830
TI  - [Treatment with sublingual desmopressin in two infants with hydranencephaly and
      central diabetes insipidus].
AB  - Central diabetes insipidus is a rare disease in children caused by a deficiency
      of vasopressin. Its main clinical manifestations are polyuria and polydipsia.
      Brain malformations are one of the main causes. Desmopressin is the synthetic
      drug of choice for the treatment. One of the routes of administration is
      sublingual and its use in infants is very limited. We describe two infants with
      central diabetes insipidus and hydranencephaly who were successfully treated with
      sublingual desmopressin.

PMID- 29333831
TI  - [Mammary hemangioma in an infant with apparent mastitis. Case report].
AB  - Mammary pathology is infrequent during childhood. It is rare the probability of
      finding a breast mass in an infant. The most frequent possible diagnoses at this
      age are breast abscess, mastitis, breast engorgement due to maternal hormonal
      stimulation and hemangioma. Reaching the proper diagnosis is essential in order
      to apply a suitable treatment and avoid the potential disease complications. We
      present the case of a female infant having a mass in the right breast from birth.
      Initially the entity was treated as mastitis. Nevertheless, the bad evolution
      made necessary considering the differential diagnosis. It was concluded to be a
      hemangioma. Due to the lesion ulceration and the potential risk of developing
      breast hypoplasia, treatment with propranolol was started. The tumor was almost
      completely resolved.

PMID- 29333832
TI  - An incidentally detected anomalous origin of the right coronary artery from the
      pulmonary artery in an infant.
AB  - Isolated anomalous origin of the right coronary artery from the main pulmonary
      artery is a rare congenital anomaly, and few cases have been reported in the
      pediatric age group. Here in, we report an asymptomatic case of a 2-month-old
      male infant who has been diagnosed as anomalous origin of the right coronary
      artery from the main pulmonary artery during the evaluation for cardiac
      abnormalities. For a suspicion on echocardiography, cardiac catheterization and
      coronary angiography performed to verify the diagnosis of anomalous origin of the
      right coronary artery from the main pulmonary artery. The patient underwent
      surgery and did well after two months follow up. Early diagnosis may prevent
      patients from cardiovascular complications.

PMID- 29333833
TI  - [Infrequent mutation in renal-coloboma syndrome: case report and review].
AB  - Renal-coloboma syndrome is an autosomal dominant disease characterized by renal
      hypodysplasia and coloboma. A case of a 12-year-old girl with chronic kidney
      disease, bilateral optic nerve colobomas and an exceptional PAX-2 gene mutation
      is presented. Diagnosed in prenatal scans with bilateral renal hypoplasia, she
      presented clinical and laboratory findings of chronic kidney disease at 5 days of
      life. Following tests showed grade II bilateral vesicoureteral reflux
      spontaneously solved, maintained non nephrotic proteinuria controlled with
      enalapril and bilateral colobomas with left macular atrophy. Renal function
      remained stable. Genetic study showed de novo and non sense mutation p.R104X in
      heterocygosis. Currently there are 80 published cases of renal-coloboma syndrome
      associated with this gene mutations. Ophthalmologic and genetic evaluations are
      crucial in cases affected by renal hypodysplasia. Renal function will establish
      prognosis. We review the etiopathogenesis of this disease.

PMID- 29333834
TI  - [Congenital esophageal stenosis: diagnosis and treatment. Cases review].
AB  - Congenital esophageal stenosis is a very rare condition and there is no standard
      treatment. We report the diagnosis, treatment and outcome of 11 patients with
      this condition managed at our institution. The most common symptom was dysphagia.
      The age at diagnosis was between 1 day and 14 years (mean age: 4.7 years). The
      esophagogram confirmed the diagnosis. Five patients presented associated
      anomalies. Four patients received surgical treatment and 7 only balloon
      dilatations. Pathologic examinations showed 3 fibromuscular stenosis and one with
      tracheobronchial remnants. All patients had a good outcome with a mean follow up
      of 4.5 years. Balloon dilatations were the definitive treatment in most of the
      patients.

PMID- 29333835
TI  - [An unintended diagnosis: Serotonergic toxicity secondary to drug interactions.
      Case reports].
AB  - Serotonin toxicity is a potentially life-threatening condition associated with
      increased serotonergic activity in the central nervous system. It is seen with
      therapeutic medication use, intentional self-poisoning and inadvertent
      interactions (SSRI-isoniazid). Although this pathology is increasingly common, it
      is not well recognized by physicians and manifestations may be wrongly attributed
      to another cause. The aim of this paper is to describe the clinical picture of a
      patient, to collaborate on diagnosis and to improve medical care of these
      patients.

PMID- 29333836
TI  - [Phakomatosis pigmentovascularis cesioflammea: a case report].
AB  - Phakomatosis pigmentovascularis (PPV) is a syndrome characterized by the
      association of a vascular nevus with a congenital pigmented lesion (epidermal
      nevus, nevus spilus, and dermal melanocytosis). There are different types of PPV
      according to the pigmentary nevus associated with the vascular malformation.
      Patients may present only the cutaneous condition or have systemic
      manifestations, among them, trauma, neurological and ophthalmological disorders.
      We report the case of a 1-year-old girl who had congenital glaucoma. On
      examination, we identified facial paralysis, bilateral ocular melanosis,
      segmental capillary vascular malformation on the face as on left trunk and
      extremities, and aberrant Mongolian spots on the upper back, lumbosacral area and
      buttocks. Due to clinical manifestation, the diagnosis of PPV was made. The
      patient was evaluated by Neurology, Traumatology and keeps on with
      ophthalmological controls. Complementary studies are important, to rule out
      extracutaneous manifestations in PPV.

PMID- 29333837
TI  - [Biodegradable airway stent for the treatment of bronchial obstruction in the
      child. Case report].
AB  - Bronchial obstruction is infrequent in the child. The main cause is malacia or
      benign stenosis. Management alternatives range from conservative treatment to
      complex surgical and/or endoscopic techniques. Placement of a stent can play a
      key role in situations where there is no other therapeutic option. However, the
      ideal stent is not yet available. In the last few years, progress has been made
      in the development and characterization of novel biodegradable materials in order
      to overcome the drawbacks of traditional stents made of silicone or metal. We
      present our experience with a new type of biodegradable airway stent in the
      treatment of severe bronchomalacia in a 2-year-old child; we evaluate safety and
      clinical effectiveness. We describe the indications and potential complications
      of pediatric endoprosthesis in the airway.

PMID- 29333838
TI  - Solitary median maxillary central incisor, holoprosencephaly and congenital nasal
      pyriform aperture stenosis in a premature infant: case report.
AB  - Solitary median maxillary central incisor syndrome is a rare disorder involving
      midline abnormalities such as holoprosencephaly, nasal cavity anomalies, cleft
      palate-lip, hypotelorism, microcephaly, and panhypopituitarism. Congenital nasal
      pyriform aperture stenosis is a lethal cause of neonatal respiratory distress due
      to narrowing of the pyriform aperture anteriorly and it can be confused with
      choanal atresia. In this report, we present a newborn infant with solitary median
      maxillary central incisor syndrome accompanied by other abnormalities including
      holoprosencephaly, nasal pyriform aperture stenosis, microcephaly and
      panhypopituitarism. Chromosomal analysis showed heterozygous SIX3 gene deletion
      at 2p21 region resulting in a more severe form of holoprosencephaly.

PMID- 29333839
TI  - [Pallister-Killian syndrome in a Mexican mestizo patient. Case report].
AB  - Pallister-Killian syndrome is caused by a tetrasomy 12p mosaicism and is
      characterized by facial dysmorphism, pigmentary skin anomalies, congenital heart
      defects, diaphragmatic hernia, epilepsy and mental retardation. The diagnosis is
      complex as the cytogenetic analysis in blood is usually normal, requiring
      karyotyping in other tissues, therefore the clinical suspicion is critical to
      guide the diagnostic tests and the patient requires an interdisciplinary clinical
      evaluation regarding the several manifestation of the syndrome. W e present the
      case of a Mexican mestizo female patient of 4 years of age referred by
      psychomotor delay and cleft palate; the clinical multidisciplinary evaluation
      demonstrated characteristics corresponding to the Pallister-Killian syndrome. The
      GTG banding karyotype analysis was normal, the skin fibroblast was
      mos47,XX,i(12)(p10)[85]/46,XX[21]. This case is an example of the importance of
      the clinical evaluation in order to establish a diagnosis that is a challenge for
      the clinical multidisciplinary team to offer medical management and genetic
      counseling.

PMID- 29333840
TI  - [Giant retroperitoneal lipoblastoma. Case report].
AB  - Lipoblastoma is part of tumors derived from adipose tissue. It is a benign
      neoplasm that can be localized or diffuse, affecting children in early childhood
      and usually located in the trunk and extremities. These tumors are uncommon in
      the pediatric age, but when one of them is present, it is a challenge that we
      must resolve quickly due to the risk of malignancy that involves other similar
      neoplastic lesions. The preoperative diagnosis is difficult, because the imaging
      methods do not provide specific information that allows us to differentiate them
      from other tumors, such as liposarcomas. The definitive diagnosis is
      anatomopathological and, in doubtful cases, cytogenetic confirmation is
      necessary. We present the case of a 14-month-old boy with diagnosis of large
      sized lipoblastoma of retroperitoneal localization.

PMID- 29333841
TI  - [Granular cell tumor of the larynx in the child. Case report].
AB  - Laryngeal tumors are uncommon in children, accounting only for 2% of the
      laryngeal anomalies. Ninety-eight percent are benign; the most frequent ones are
      recurrent respiratory papillomatosis and haemangioma. Granular cell tumor, also
      called Abrikossoff tumor, is an unusual benign neoplasm, especially in the
      larynx. Clinical manifestations depend on the size and location of the tumor.
      Dysphonia is the main presenting symptom. The diagnosis is confirmed by the
      biopsy. The treatment of choice is surgery. We present a 9-year-old girl with
      dysphonia and exertion dyspnea due to a granular cell tumor of the larynx, and we
      emphasize the importance of considering the endoscopic evaluation of the airway
      in every child with progressive or persistent dysphonia in order to determine the
      etiology.

PMID- 29333842
TI  - An adolescent with idiopathic pleuroparenchymal fibroelastosis. Case report.
AB  - Idiopathic pleuroparenchymal fibroelastosis (IPPFE) is a rare disorder recently
      included in rare idiopathic interstitial pneumonias according to the updated
      American Thoracic Society/European Respiratory Society classification. IPPFE is
      characterized by pleural and subpleural parenchymal fibrosis causing volume loss
      predominantly in the upper lung lobes. Age of onset is variable, IPPFE mainly
      occurs in third and fourth decades. We present a 16 year old patient with a 2
      year history of exertional dyspnea, nonproductive cough and weight loss. On
      physical examination, auscultation revealed diminished breath sounds on the upper
      lobes. Chest radiograph showed apical pleural thickening and volume loss.
      Computerized tomographic scan (CT) of chest revealed ground glass densities and
      tubular bronchiectasis predominantly in upper lobes bilaterally, with
      interlobular septal thickening of the pleura and enlarged mediastinal lymph
      nodes. Thoracoscopic lung biopsy was performed and histological evaluation showed
      subpleural fibrosis and elastic staining demonstrated fragmented elastic fiber
      deposition in the subpleural area and adjacent pulmonary parenchyma suggesting
      IPPFE. To our knowledge this is the first case in childhood. Therefore,
      pediatricians should be aware of this disease for the diagnosis and appropriate
      management.

PMID- 29333843
TI  - [Use of the identification bracelet in the newborn. A safe method?]
AB  - BACKGROUND: The placement of newborn bracelets is the most widely used method for
      patient identification in Argentina. OBJECTIVES: To evaluate the permanence of
      the identification bracelets during the hospitalization. POPULATION: All the term
      newborns who remained with their mother. Design: observational, prospective
      study, cohort type, randomized: forearm, leg. RESULTS: Cases observed: 914.
      Forearm: 457, leg: 438. At the time of discharge, the frequency of permanence of
      the identification bracelets as originally placed was 67% in the forearm and 72%
      in the leg. CONCLUSIONS: A third of newborns lacked the bracelet as originally
      placed at the time of discharge. The permanence was higher in the leg.

PMID- 29333844
TI  - [Success in probing for congenital nasolacrimal duct obstruction. Ten years
      experience].
AB  - INTRODUCTION: The congenital nasolacrimal duct obstruction is a common pathology,
      with low morbidity, but not exempt of complications without the correct diagnosis
      and management. METHODS: Retrospective study from 2005 to 2015 in patients who
      were submitted to a probing procedure. We identified age at procedure, gender,
      laterality and presence or absence of success with the procedure. RESULTS: One
      hundred thirty-seven eyes were analyzed. The median age was 17 months and the
      total success rate was 85.4%. CONCLUSION: In congenital nasolacrimal duct
      obstruction there is a high rate of spontaneous resolution with the proper
      initial conservative management and, in patients older than 12 months, probing
      has a high rate of success.

PMID- 29333845
TI  - [Script Concordance Test: first nationwide experience in pediatrics].
AB  - The Script Concordance Test is a suitable test for assessing clinical reasoning
      in postgraduate medical education. We present the first nationwide, realtime, web
      based experience of a Script Concordance Test administered to 3rd year pediatric
      residents. The test was administered to 268 residents (postgraduate year 3), from
      56 different programs, requiring 46.1 +/- 27.1 minutes to complete it, and
      scoring 65.3 +/- 7.47 points. A later survey showed limited satisfaction from
      participants. This experience showed that this kind of test is feasible in this
      setting.

PMID- 29333846
TI  - [Food allergy in children: recommendations for diagnosis and treatment].
AB  - Food allergy arises from a specific immune response induced by food exposure. It
      is the first cause of anaphylaxis in childhood. Its prevalence increased
      exponentially in western countries. The proteins most frequently involved in
      infants are cow's milk and hen's egg; and in adults, seafood. Peanuts have the
      same frequency in both groups. The clinical manifestations and methodology of
      study are directly related to the pathophysiology of the disease. Clinical
      history, skin prick test, patch test, and food oral challenge are essential to
      arrive at a correct diagnosis, that will avoid unnecessary exclusions or
      exposures that carry life risk. The treatment is based on the correct avoidance
      of responsible food (considering hidden allergens), besides patient and their
      care giver's education, to maintain a good quality of life.

PMID- 29333847
TI  - A Rare Cause of Acute Pancreatitis: Gastrostomy Catheter Migration.

PMID- 29333848
TI  - Highly Stable and Luminescent Perovskite-Polymer Composites from a Convenient and
      Universal Strategy.
AB  - Extensive attention has been received in recent years for perovskite-polymer
      composites because of their combination of properties from polymers and
      perovskites. In this work, a convenient and universal strategy is reported to
      prepare cesium lead bromide or organolead halide methylammonium bromide polymer
      composites. This technique integrates the formation of perovskite crystals and
      the polymer matrix in a one-pot reaction, avoiding the tedious separation and
      preparation of perovskites. The method is universal for most of the commercially
      available monomers and polymers, which has been verified in this report using
      poly(methyl methacrylate), poly(butyl methacrylate), and polystyrene. The
      physical properties of the varied polymers lead to different luminescent
      properties and stabilities of the composites. No organic solvent is required
      during the preparation, indicating a green technique for the composites.
      Additionally, the resulted perovskite-polymer composites are extraordinarily
      stable, maintaining their quantum yield for more than 1 month in air. On the
      basis of the above properties, a prototype of white light-emitting diodes was
      successfully constructed with feasible color characters and narrow bandwidths.
      Furthermore, large-area (dimension: 10 * 7 * 0.15 cm) perovskite-polymer plates
      are easily prepared via the one-pot strategy, showing that the technique is ready
      for possible large-area optical devices. This work provides an efficient
      technique toward various kinds of perovskite-polymer composites for both
      scientific research studies and future applications.

PMID- 29333849
TI  - Asymmetric Conjugate Addition of alpha-Cyanoketones to Enones Using
      Diaminomethylenemalononitrile Organocatalyst.
AB  - A diaminomethylenemalononitrile organocatalyst efficiently catalyzed the
      asymmetric conjugate addition of alpha-cyanoketones to vinyl ketones to give the
      corresponding 1,5-dicarbonyl compounds, which bear an all-carbon quaternary
      stereogenic center with high enantioselectivities. This report is the first
      example of the asymmetric conjugate addition of alpha-cyanoketones to vinyl
      ketones using an organocatalyst.

PMID- 29333850
TI  - Engineering NiS/Ni2P Heterostructures for Efficient Electrocatalytic Water
      Splitting.
AB  - Developing high-active and low-cost bifunctional materials for catalyzing the
      hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) holds a
      pivotal role in water splitting. Therefore, we present a new strategy to form
      NiS/Ni2P heterostructures. The as-obtained NiS/Ni2P/carbon cloth (CC) requires
      overpotentials of 111 mV for the HER and 265 mV for the OER to reach a current
      density of 20 mA cm-2, outperforming their counterparts such as NiS and Ni2P
      under the same conditions. Additionally, the NiS/Ni2P/CC electrode requires a
      1.67 V cell voltage to deliver 10 mA cm-2 in a two-electrode electrolysis system,
      which is comparable to the cell using the benchmark Pt/C||RuO2 electrode.
      Detailed characterizations reveal that strong electronic interactions between NiS
      and Ni2P, abundant active sites, and smaller charge-transfer resistance
      contribute to the improved HER and OER activity.

PMID- 29333852
TI  - Synthesis of Molecularly Imprinted Polymer Nanoparticles for alpha-Casein
      Detection Using Surface Plasmon Resonance as a Milk Allergen Sensor.
AB  - Food recalls due to undeclared allergens or contamination are costly to the food
      manufacturing industry worldwide. As the industry strives for better
      manufacturing efficiencies over a diverse range of food products, there is a need
      for the development of new analytical techniques to improve monitoring of the
      presence of unintended food allergens during the food manufacturing process. In
      particular, the monitoring of wash samples from cleaning in place systems (CIP),
      used in the cleaning of food processing equipment, would allow for the effective
      removal of allergen containing ingredients in between food batches. Casein
      proteins constitute the biggest group of proteins in milk and hence are the most
      common milk protein allergen in food ingredients. As such, these proteins could
      present an ideal analyte for cleaning validation. In this work, molecularly
      imprinted polymer nanoparticles (nanoMIPs) with high affinity toward bovine alpha
      casein were synthesized using a solid-phase imprinting method. The nanoMIPs were
      then characterized and incorporated into label free surface plasmon resonance
      (SPR) based sensor. The nanoMIPs demonstrated good binding affinity and
      selectivity toward alpha-casein (KD ~ 10 * 10-9 M). This simple affinity sensor
      demonstrated the quantitative detection of alpha-casein achieving a detection
      limit of 127 +/- 97.6 ng mL-1 (0.127 ppm) which is far superior to existing
      commercially available ELISA kits. Recoveries from spiked CIP wastewater samples
      were within the acceptable range (87-120%). The reported sensor could allow food
      manufacturers to adequately monitor and manage food allergen risk in food
      processing environments while ensuring that the food produced is safe for the
      consumer.

PMID- 29333851
TI  - Oxygen Vacancy Dynamics at Room Temperature in Oxide Heterostructures.
AB  - Oxygen vacancy dynamic behavior at room temperature in complex oxides was
      carefully explored by using a combined approach of ion liquid gating technique
      and resistance measurements. Heterostructures of PrBaCo2O5+delta/Gd2O3-doped CeO2
      epitaxial thin films were fabricated on (001) Y2O3-stabilized ZrO2 single crystal
      substrates for systematically investigating the oxygen redox dynamics. The oxygen
      dynamic changes as response to the gating voltage and duration were precisely
      detected by in situ resistance measurements. A reversible and nonvolatile
      resistive switching dynamics was detected at room temperature under the gating
      voltage >13.5 V with pulse duration >1 s.

PMID- 29333853
TI  - Highly Sensitive and Very Stretchable Strain Sensor Based on a Rubbery
      Semiconductor.
AB  - There is a growing interest in developing stretchable strain sensors to quantify
      the large mechanical deformation and strain associated with the activities for a
      wide range of species, such as humans, machines, and robots. Here, we report a
      novel stretchable strain sensor entirely in a rubber format by using a solution
      processed rubbery semiconductor as the sensing material to achieve high
      sensitivity, large mechanical strain tolerance, and hysteresis-less and highly
      linear responses. Specifically, the rubbery semiconductor exploits pi-pi stacked
      poly(3-hexylthiophene-2,5-diyl) nanofibrils (P3HT-NFs) percolated in silicone
      elastomer of poly(dimethylsiloxane) to yield semiconducting nanocomposite with a
      large mechanical stretchability, although P3HT is a well-known nonstretchable
      semiconductor. The fabricated strain sensors exhibit reliable and reversible
      sensing capability, high gauge factor (gauge factor = 32), high linearity (R2 >
      0.996), and low hysteresis (degree of hysteresis <12%) responses at the
      mechanical strain of up to 100%. A strain sensor in this format can be scalably
      manufactured and implemented as wearable smart gloves. Systematic investigations
      in the materials design and synthesis, sensor fabrication and characterization,
      and mechanical analysis reveal the key fundamental and application aspects of the
      highly sensitive and very stretchable strain sensors entirely from rubbers.

PMID- 29333854
TI  - Cucurbit[8]uril-Based Giant Supramolecular Vesicles: Highly Stable, Versatile
      Carriers for Photoresponsive and Targeted Drug Delivery.
AB  - Highly stable giant supramolecular vesicles were constructed by hierarchical self
      assembly of cucurbit[8]uril (CB[8])-based supra-amphiphiles for photoresponsive
      and targeted intracellular drug delivery. These smart vesicles can encapsulate
      the model drugs with high loading efficiencies and then release them by
      manipulating photoswitchable CB[8] heteroternary complexation to regulate the
      formation and dissociation of supra-amphiphiles that cause dramatic morphological
      changes of the assemblies to achieve remote optically controlled drug delivery.
      More importantly, the confocal microscopy analysis, cellular uptake experiment,
      and cell viability assay have shown that the giant vesicles are able to maintain
      the structural integrity and stability within actual cellular environments and
      exhibit obvious advantages for intracellular drug delivery such as low toxicity,
      easy surface modification for tumor-targeting selectivity, and rapid
      internalization into different human cancer cell lines. A synergistic mechanism
      that integrates multiple pathways including energy-dependent endocytosis,
      macropinocytosis, cholesterol-dependent endocytosis, and microtubule-related
      endocytosis was determined to facilitate the internalization process. Moreover,
      cytotoxicity experiments and flow cytometric analysis have demonstrated that the
      doxorubicin hydrochloride-loaded vesicles exhibited a significant therapeutic
      effect for tumor cells upon UV light irradiation, which makes the photoresponsive
      system more promising for potential applications in pharmaceutically relevant
      fields.

PMID- 29333855
TI  - Carbon- and Binder-Free Core-Shell Nanowire Arrays for Efficient Ethanol Electro
      Oxidation in Alkaline Medium.
AB  - To achieve high electrochemical surface area (ECSA) and avoid carbon support and
      binder in the anode catalyst of direct ethanol fuel cell, herein, we design
      freestanding core-shell nickel@palladium-nickel nanowire arrays (Ni@Pd-Ni NAs)
      without carbon support and binder for high-efficiency ethanol electro-oxidation.
      Bare Ni nanowire arrays (Ni NAs) are first prepared using the facile template
      assistant electrodeposition method. Subsequently, the Ni@Pd-Ni NAs are formed
      using one-step solution-based alloying reaction. The optimized Ni@Pd-Ni NA
      electrode with a high ECSA of 64.4 m2 g-1Pd exhibits excellent electrochemical
      performance (peak current density: 622 A g-1Pd) and cycling stability for ethanol
      electro-oxidation. The facilely obtained yet high-efficiency core-shell Ni@Pd-Ni
      NA electrode is a promising electrocatalyst, which can be utilized for oxygen
      reduction reaction, urea, hydrazine hydrate, and hydrogen peroxide electro
      oxidation, not limited to the ethanol electro-oxidation.

PMID- 29333856
TI  - Analysis of the pH-Dependent Fe(III) Ion Chelating Activity of Anthocyanin
      Extracted from Black Soybean [Glycine max (L.) Merr.] Coats.
AB  - The Fe(III) chelating activity of anthocyanin extracted from black soybean coats
      was investigated at pH 3.0, 5.0, 6.5, 7.0, and 7.4 with fluorescence spectroscopy
      and microscale thermophoresis (MST). Cyanidin-3-glucoside (C3G) was determined to
      be 98% of the total anthocyanin by high-performance liquid chromatography. The
      binding affinity (Ka) exhibited significant pH-dependent behavior: Ka was 9.7167
      * 104, 1.0837 * 104, 1.4284 * 104, 5.4550 * 104, and 3.0269 * 104 M-1 at pH 3.0,
      5.0, 6.5, 7.0, and 7.4, respectively (p < 0.05). The MST data showed that DeltaG
      < 0 and DeltaH < 0, demonstrating that chelation is spontaneous and exothermic.
      Because both DeltaH and DeltaS < 0, the chelation involves hydrogen bonds and/or
      van der Waals forces for pH 3.0, 5.0, and 6.5. Electrostatic interactions
      contributed to chelation at pH 7.0 and 7.4 with DeltaH < 0 and DeltaS > 0. With
      the formation of chelates, C3G improved the solubility of Fe(III) at pH 6.5, 7.0,
      and 7.4 to enhance the ferric ion bioavailability, except for aggregation
      observed at pH 5.0.

PMID- 29333857
TI  - Active Site Revealed for Water Oxidation on Electrochemically Induced delta-MnO2:
      Role of Spinel-to-Layer Phase Transition.
AB  - Seeking for active MnOx material as artificial water splitting catalyst has been
      a long history since the discovery of PSII system in nature. To date, the highest
      activity MnOx catalyst reported for oxygen evolution reaction (OER) does however
      not belong to common MnO2 polymorphs (alpha-, beta-, delta-MnO2), but rather to
      nascent delta-MnO2 layer produced in situ from spinel under electrochemical
      conditions with unknown active site structure. Here with the stochastic surface
      walking (SSW) pathway sampling method, we for the first time resolve the atomic
      level mechanism of spinel-to-layer Mn3O4 solid phase transition in aqueous
      electrolyte. We show that a transient H0.5MnO2 phase is the precursor of
      transition that forms at high voltage (>1 V), and it undergoes the solid-to-solid
      phase transition to produce a delta-MnO2 layer, which is accompanied by Mn
      dissolution, dislocation, layer-breaking, and insertion of water/cations between
      layers. This leads to the generation of a variety of possible defective
      structures. We demonstrate using first-principles calculations that a special
      edge site with neighboring Mn vacancy provides the best OER activity with an
      overpotential of 0.59 V, 0.19 V lower than that of pristine MnO2. The high
      activity of such Mn sites are attributed to its special local structure:
      pseudocubane with one corner missing. The presence of the Mn vacancy near the
      active site enhances the adsorption of OH intermediate in OER. This defective
      cubane structure shares the common geometrical and electronic features found in
      the PSII system.

PMID- 29333858
TI  - Mineral- and Base-Catalyzed Hydrolysis of Organophosphate Flame Retardants:
      Potential Major Fate-Controlling Sink in Soil and Aquatic Environments.
AB  - The ubiquitous occurrence of organophosphate flame retardants (OPFRs) in aquatic
      and soil environments poses significant risks to human health and ecosystems.
      Here, we report on the hydrolysis of six OPFRs and three structural analogues in
      the absence and presence of metal (hydr)oxide minerals. Eight of the target
      compounds showed marked degradation in alkaline solutions (pH 9-12) with half
      lives ranging from 0.02-170 days. Kinetics follow a second-order rate law with
      apparent rate constants for base-catalyzed hydrolysis (kB) ranging from 0.69-42
      000 M-1 d-1. Although hydrolysis in homogeneous solution at circumneutral pH is
      exceedingly slow (t1/2 > 2 years, except for tris(2,2,2-trichloroethy)
      phosphate), rapid degradation is observed in the presence of metal (hydr)oxide
      minerals, with half-lives reduced to <10 days for most of the target OPFRs in
      mineral suspensions (15 m2/L mineral surface area loading). LC-qToF-MS analysis
      of transformation products confirmed ester hydrolysis as the active degradation
      pathway. Values of kB for individual OPFRs are highly variable and correlate with
      acid dissociation constants (pKa) of the corresponding alcohol leaving groups. In
      contrast, kinetic parameters for mineral-catalyzed reactions are much less
      sensitive to OPFR structure, indicating that other factors like mineral-OPFR
      interactions are rate controlling. Given the documented recalcitrance of OPFRs to
      biodegradation and photodegradation, these results suggest that mineral-catalyzed
      hydrolysis may be a major fate-controlling sink in natural environments.

PMID- 29333859
TI  - Chromatographic Separation and Visual Detection on Wicking Microfluidic Devices:
      Quantitation of Cu2+ in Surface, Ground, and Drinking Water.
AB  - Copper is widely applied in industrial and technological applications and is an
      essential micronutrient for humans and animals. However, exposure to high
      environmental levels of copper, especially through drinking water, can lead to
      copper toxicity, resulting in severe acute and chronic health effects. Therefore,
      regular monitoring of aqueous copper ions has become necessary as recent
      anthropogenic activities have led to elevated environmental concentrations of
      copper. On-site monitoring processes require an inexpensive, simple, and portable
      analytical approach capable of generating reliable qualitative and quantitative
      data efficiently. Membrane-based lateral flow microfluidic devices are ideal
      candidates as they facilitate rapid, inexpensive, and portable measurements. Here
      we present a simple, chromatographic separation approach in combination with a
      visual detection method for Cu2+ quantitation, performed in a lateral flow
      microfluidic channel. This method appreciably minimizes interferences by
      incorporating a nonspecific polymer inclusion membrane (PIM) based assay with a
      "dot-counting" approach to quantification. In this study, hydrophobic
      polycaprolactone (PCL)-filled glass microfiber (GMF) membranes were used as the
      base substrate onto which the PIM was evenly dispensed as an array of dots. The
      devices thus prepared were then selectively exposed to oxygen radicals through a
      mask to generate a hydrophilic surface path along which the sample was wicked.
      Using this approach, copper concentrations from 1 to 20 ppm were quantified from
      5 MUL samples using only visual observation of the assay device.

PMID- 29333860
TI  - Copper(II)-Mediated ortho-Selective C(sp2)-H Tandem Alkynylation/Annulation and
      ortho-Hydroxylation of Anilides with 2-Aminophenyl-1H-pyrazole as a Directing
      Group.
AB  - 2-Aminophenyl-1H-pyrazole has been identified as a viable directing group to
      promote copper(II)-mediated ortho-selective sp2 C-H bond tandem
      alkynylation/annulation of anilides with terminal alkynes to offer arylmethylene
      isoindolinones. Meanwhile, copper(II)-mediated ortho-selective sp2 C-H
      hydroxylation of anilides has also been optimized as the major reaction pathway
      by using Cu(OAc)2 as the promoter and 1,1,3,3-tetramethylguanidine as an organic
      base. Recovery of the directing group was achieved by hydrazinolysis for
      arylmethylene isoindolinones and basic hydrolysis for the hydroxylation products.

PMID- 29333861
TI  - Intra- and inter-observer agreement in the visual interpretation of interim 18F
      FDG PET/CT in malignant lymphoma: influence of clinical information.
AB  - Background Interim PET/CT is widely performed in lymphoma patients in clinical
      practice and clinical trials. Visual assessment using a 5-point scale is proposed
      for PET/CT interpretation, but intra- and inter-observer variation is not fully
      investigated. Purpose To investigate intra- and inter-observer variations in the
      reporting of interim positron emission tomography/computed tomography (PET/CT) in
      lymphoma patients, and the influence of clinical information on the
      interpretation. Material and Methods Three expert readers from different
      institutions interpreted interim PET/CT images of 42 consecutive patients with
      malignant lymphoma twice, with and without clinical information. The intra- and
      inter-observer agreements were calculated using the kappa statistic on a patient
      and a region basis. Results On a patient basis, intra-observer agreement, inter
      observer agreement without information, and inter-observer agreement with
      information were within the ranges 0.48-0.62, 0.51-0.62, and 0.42-0.76,
      respectively. In the evaluation of lymph nodes, intra-observer agreement, inter
      observer agreement without information, and inter-observer agreement with
      information were within the ranges 0.78-0.92, 0.80-0.82, and 0.77-0.83,
      respectively. Observer agreements were in almost perfect to substantial agreement
      categories for most lymphatic organs, but were generally low for the other
      organs. Conclusion The intra- and inter-observer agreements in evaluating interim
      PET/CT were relatively low for extranodal lesions, but they were substantial to
      almost perfect when interpreting nodal regions in malignant lymphoma,
      irrespective of the provision of clinical information, although memory at the
      first interpretation might have affected the intra-observer results.

PMID- 29333862
TI  - Pharmacokinetic determination and analysis of nortriptyline based on GC-MS
      coupled with hollow-fiber drop-to-drop solvent microextraction technique.
AB  - AIM: A simple, sensitive and robust technique of hollow-fiber drop-to-drop
      solvent microextraction coupled with GC-MS has been successfully developed for
      the detection of antidepressant drug nortriptyline in human blood and urine
      samples. The recoveries of the drug from the spiked samples are found to be well
      within the range and appropriate to support the method. RESULTS: The LOD for the
      drug was obtained to be 0.007, 0.009 and 0.021 MUg ml-1 in deionized water, urine
      and blood samples of human subjects, respectively. Linearity was obtained over
      the concentration range of 0.5-5.0 mg l-1 in deionized water with correlation
      coefficient 0.99672.

PMID- 29333863
TI  - Principles of vaccine potency assays.
AB  - Compared with biologics, vaccine potency assays represent a special challenge due
      to their unique compositions, multivalency, long life cycles and global
      distribution. Historically, vaccines were released using in vivo potency assays
      requiring immunization of dozens of animals. Modern vaccines use a variety of
      newer analytical tools including biochemical, cell-based and immunochemical
      methods to measure potency. The choice of analytics largely depends on the
      mechanism of action and ability to ensure lot-to-lot consistency. Live vaccines
      often require cell-based assays to ensure infectivity, whereas recombinant
      vaccine potency can be reliably monitored with immunoassays. Several case studies
      are presented to demonstrate the relationship between mechanism of action and
      potency assay. A high-level decision tree is presented to assist with assay
      selection.

PMID- 29333864
TI  - Non-digestible carbohydrates in infant formula as substitution for human milk
      oligosaccharide functions: Effects on microbiota and gut maturation.
AB  - Human milk (HM) is the golden standard for nutrition of newborn infants. Human
      milk oligosaccharides (HMOs) are abundantly present in HM and exert multiple
      beneficial functions, such as support of colonization of the gut microbiota,
      reduction of pathogenic infections and support of immune development. HMO
      composition is during lactation continuously adapted by the mother to accommodate
      the needs of the neonate. Unfortunately, for many valid reasons not all neonates
      can be fed with HM and are either totally or partly fed with cow-milk derived
      infant formulas, which do not contain HMOs. These cow-milk formulas are
      supplemented with non-digestible carbohydrates (NDCs) that have functional
      effects similar to that of some HMOs, since production of synthetic HMOs is
      challenging and still very expensive. However, NDCs cannot substitute all HMO
      functions. More efficacious NDCs may be developed and customized for specific
      groups of neonates such as pre-matures and allergy prone infants. Here current
      knowledge of HMO functions in the neonate in view of possible replacement of HMOs
      by NDCs in infant formulas is reviewed. Furthermore, methods to expedite
      identification of suitable NDCs and structure/function relationships are reviewed
      as in vivo studies in babies are impossible.

PMID- 29333865
TI  - Parental supervision and discomfort with children walking to school in low-income
      communities in Cape Town, South Africa.
AB  - OBJECTIVE: The risk of pedestrian injury is compounded for children living in low
      income communities due to factors such as poor road and pedestrian
      infrastructure, reliance on walking as a means of transport, and compromised
      supervision. Parents play an important role in child pedestrian safety. The
      primary objective of this study was to examine the effects of child pedestrian
      variables on parental discomfort with regard to letting their child walk to and
      from school and on the frequency of adult supervision. METHODS: A cross-sectional
      study was conducted using a convenience sample from 3 schools participating in a
      pedestrian safety school initiative. The schools are situated in low-income, high
      risk communities in the City of Cape Town. A parent survey form was translated
      into isiXhosa and sent home with learners to those parents who had consented to
      participate. The response rate was 70.4%, and only parents of children who walk
      to and from school were included in the final sample (n = 359). Child pedestrian
      variables include the time taken to walk to school, parental rating of the
      child's ability to safely cross the road, and the frequency of adult supervision.
      RESULTS: More than half of parents reported that their child walked to and from
      school without adult supervision. About 56% of children took less than 20 min to
      walk to school. Most parents (61%) were uncomfortable with their child walking to
      school, although the majority of parents (55.7%) rated their child's ability to
      cross the road safely as better or significantly better than average (compared to
      peers). The parents did not perceive any differences in pedestrian risk factors
      between boys and girls or between younger (6-9 years) and older (10-15 years)
      children. The time spent by a child walking to school and parents' perceptions of
      their child's road-crossing ability were found to be significant predictors of
      parental discomfort (in letting their child walk). Younger children and children
      who spent less time walking were more likely to be supervised by an adult.
      CONCLUSIONS: Many South African schoolchildren have to navigate the roads without
      adult supervision from a young age. Caregivers, especially in low-income
      settings, often have limited options with regard to getting their child to school
      safely. Regardless of the child's age and gender, the time that they spend on the
      roads is an important factor for parents in terms of pedestrian safety.

PMID- 29333867
TI  - What is the meaning of filial piety for people with dementia and their family
      caregivers in China under the current social transitions? An interpretative
      phenomenological analysis.
AB  - The filial piety model of family centred care has dominated Chinese society for
      thousands of years. The ways in which filial piety is presented are being
      modified and modernised as China undergoes social transitions. The study aims to
      understand the meaning of filial piety for people with dementia and family
      caregivers. Semi-structured interviews with people with dementia ( n = 10) and
      family caregivers ( n = 14) were conducted. Data were analysed using
      interpretative phenomenological analysis. Three themes emerged: (a) 'Being filial
      is a cultural continuity and my future investment'. (b) 'The changed perception
      and ways of being filial'. (c) 'Filial responsibility is a social and cultural
      convention, but not my personal choice'. This study highlights the importance of
      cultural values in family care decision making and in shaping filial
      responsibilities. It indicates that filial obligation can be maintained through
      social support, even though the nature of filial piety has been changed by social
      transitions.

PMID- 29333866
TI  - Offline derivatization LC-MS/MS method for simultaneous estimation of vanillin
      and vanillic acid in guinea pig plasma.
AB  - AIM: Vanillin used as a positive control substrate of aldehyde oxidase activity
      gets metabolized to vanillic acid. Low MW and low sensitivity in negative ion
      mode are challenges with these analytes. Our objective was to develop a simple
      offline derivatization LC-MS/MS method to address these challenges.
      METHODOLOGY/RESULTS: A simple dansyl chloride derivatization of the phenolic
      groups on vanillin and vanillic acid was adopted to enable easy ionization in
      commonly used acidic mobile phases. Calibration curves were linear over the
      concentrations of 4.88-1250 nM with an LLOQ of 0.64 fmoles on column for both
      analytes. CONCLUSION: The qualified method was successfully applied to
      simultaneously measure vanillin and vanillic acid in plasma and urine from a
      guinea pig pharmacokinetic study.

PMID- 29333868
TI  - Drug detection in biological specimens: recent colorimetric methods.

PMID- 29333869
TI  - Quantitation of saxitoxin in human urine using immunocapture extraction and LC
      MS.
AB  - AIM: An immunomagnetic capture protocol for use with LC-MS was developed for the
      quantitation of saxitoxin (STX) in human urine. MATERIALS & METHODS: This method
      uses monoclonal antibodies coupled to magnetic beads. STX was certified reference
      material grade from National Research Council, Canada. Analysis was carried out
      using LC-MS. RESULTS: With an extraction efficiency of 80%, accuracy and
      precision of 93.0-100.2% and 5.3-12.6%, respectively, and a dynamic range of 1.00
      100 ng/ml, the method is well suited to quantify STX exposures based on
      previously reported cases. CONCLUSION: Compared with our previously published
      protocols, this method has improved selectivity, a fivefold increase in
      sensitivity and uses only a third of the sample volume. This method can diagnose
      future toxin exposures and may complement the shellfish monitoring programs
      worldwide.

PMID- 29333870
TI  - The effects of aerobic exercise for persons with migraine and co-existing tension
      type headache and neck pain. A randomized, controlled, clinical trial.
AB  - Aim To evaluate aerobic exercise in migraine and co-existing tension-type
      headache and neck pain. Methods Consecutively recruited persons with migraine and
      co-existing tension-type headache and neck pain were randomized into an exercise
      group or control group. Aerobic exercise consisted of bike/cross-trainer/brisk
      walking for 45 minutes, three times/week. Controls continued usual daily
      activities. Pain frequency, intensity, and duration; physical fitness, level of
      physical activity, well-being and ability to engage in daily activities were
      assessed at baseline, after treatment and at follow-up. Results Fifty-two persons
      completed the study. Significant between-group improvements for the exercise
      group were found for physical fitness, level of physical activity, migraine
      burden and the ability to engage in physical activity because of reduced impact
      of tension-type headache and neck pain. Within the exercise group, significant
      reduction was found for migraine frequency, pain intensity and duration, neck
      pain intensity, and burden of migraine; an increase in physical fitness and well
      being. Conclusions Exercise significantly reduced the burden of migraine and the
      ability to engage in physical activity because of reduced impact of tension-type
      headache and neck pain. Exercise also reduced migraine frequency, pain intensity
      and duration, although this was not significant compared to controls. These
      results emphasize the importance of regular aerobic exercise for reduction of
      migraine burden.

PMID- 29333871
TI  - Drug monitoring by volumetric absorptive microsampling: method development
      considerations to mitigate hematocrit effects.
AB  - AIM: GSKA is a compound that was in development in clinical trials. A bioanalysis
      method to quantify GSKA using volumetric absorptive microsampling (VAMS) was
      developed and hematocrit (HCT) related assay bias was investigated. METHODOLOGY:
      After accurate sampling of 10 MUl blood, VAMS tips were air dried approximately
      18 h and desorbed by an aqueous solution containing internal standard. The
      recovered blood underwent liquid-liquid extraction in ethyl acetate to minimize
      matrix suppression. Assay accuracy, precision, linearity, carryover, selectivity,
      recovery, matrix effects, HCT effects and long-term quality control stability
      were evaluated. CONCLUSION: HCT-related assay bias was minimized in 30-60% blood
      HCT range, and all validation parameters met acceptance criteria. The method is
      suitable for quantitative analysis of GSKA in human blood.

PMID- 29333872
TI  - Effects and underlying mechanisms of unstable shoes on chronic low back pain: a
      randomized controlled trial.
AB  - OBJECTIVE: To investigate the effects that wearing unstable shoes has on
      disability, trunk muscle activity, and lumbar spine range of motion (ROM) in
      patients with chronic lower back pain (CLBP). DESIGN: Randomized controlled
      trial. SETTING: Orthopedic Surgery Service. PARTICIPANTS: We randomized 40 adults
      with nonspecific CLBP either to an unstable shoes group ( n = 20) or to the
      control group ( n = 20). INTERVENTION: The participants in the unstable shoes
      group were advised to wear these shoes for a minimum of six hours a day for four
      weeks. Control group participants were asked to continue wearing their regular
      shoes. OUTCOME MEASURES: Our primary outcome was measurement of back-related
      dysfunction, assessed using the Roland-Morris Disability Questionnaire. Secondary
      outcomes included changes in electromyographic (EMG) activity of erector spinae
      (ES), rectus abdominis (RA), internus obliquus (IO), and externus obliquus (EO)
      muscles, and changes in lumbar spine ROM. RESULTS: Between-group analysis
      highlighted a significant decrease in disability in the unstable shoes group
      compared to the control (-5, 95% confidence interval (CI) = -8.4 to -1.6). Our
      results revealed a significant increase in the percentage of RA, ES, IO, and EO
      EMG activity and in lumbar spine ROM in the unstable shoes group compared to the
      control group. Moreover, our results showed a significant negative correlation
      between disability and the percentage of ES, RA, and IO muscle activity at the
      end of the intervention. CONCLUSION: This study shows that the use of unstable
      shoes contributes to improvements in disability, which are likely related to
      increased trunk muscle activity and lumbar spine ROM.

PMID- 29333873
TI  - Survey regarding the 0.05 blood alcohol concentration limit for driving in the
      United States.
AB  - BACKGROUND: On May 14, 2013, the National Transportation Safety Board (NTSB)
      proposed that states lower the blood alcohol concentration (BAC) illegal limit
      from 0.08 to 0.05 g/dL (also referred to as the 0.08 law and the 0.05 limit,
      respectively). In March 2017, this recommendation was signed into law in the
      State of Utah. OBJECTIVE: The objective of this survey is to investigate
      perceptions regarding enforcement of the 0.05 g/dL BAC limit. METHOD: Opinions of
      law enforcement officers, prosecutors, and defense attorneys were obtained
      through a series of questionnaires and focus groups. RESULTS: Survey data were
      collected from 32 law enforcement officers, 20 prosecutors, and 4 defense
      attorneys. The participants rated the usefulness of the NHTSA's driving while
      intoxicated (DWI) driving cues lower for the 0.05 limit than for the 0.08 law.
      Some of the participants believed that training would be needed in regard to
      sobriety testing under the 0.05 limit. Participants also stated that adequately
      preparing for prosecution of drunk drivers would be more difficult under the 0.05
      limit. In addition, it was believed that drunk driving cases are more likely to
      be withdrawn and fewer plea agreements and guilty pleas are likely under the 0.05
      limit. Prosecutors were concerned that the 0.05 limit would result in poorly
      investigated cases and overburden the court system. Defense attorneys were
      concerned about the social and economic costs of a 0.05 limit. DISCUSSION:
      Overall, it appears that the 0.05 limit is viewed as enforceable and it will save
      lives; however, the usefulness of the NHTSA DWI Detection Guide and of the
      standardized field sobriety tests need to be established for lower BACs, and
      efforts must be made to educate people regarding the relationship between BAC and
      impairment and impairment and driving with the risk of injury and death.
      CONCLUSION: Though the 0.05 limit offers promise in saving lives, the following
      issues associated with changing the limit to 0.05 need to be resolved prior to
      implementation: Validating the sobriety tests for the 0.05 limit; if needed,
      modifying the sobriety tests to make them effective and valid at the 0.05 limit;
      and training law enforcement personnel and educating the public regarding the
      0.05 limit.

PMID- 29333874
TI  - Road traffic injuries among riders of electric bike/electric moped in southern
      China.
AB  - OBJECTIVE: Electric bike/moped-related road traffic injuries have become a
      burgeoning public health problem in China. The objective of this study was to
      identify the prevalence and potential risk factors of electric bike/moped-related
      road traffic injuries among electric bike/moped riders in southern China.
      METHODS: A cross-sectional study was used to interview 3,151 electric bike/moped
      riders in southern China. Electric bike/moped-related road traffic injuries that
      occurred from July 2014 to June 2015 were investigated. Data were collected by
      face-to-face interviews and analyzed between July 2015 and June 2017. RESULTS:
      The prevalence of electric bike/moped-related road traffic injuries among the
      investigated riders was 15.99%. Electric bike/moped-related road traffic injuries
      were significantly associated with category of electric bike (adjusted odds ratio
      [AOR] = 1.36, 95% confidence interval [CI], 1.01-1.82), self-reported confusion
      (AOR = 1.77, 95% CI, 1.13-2.78), history of crashes (AOR = 6.14, 95% CI, 4.68
      8.07), running red lights (AOR = 3.57, 95% CI, 2.42-5.25), carrying children
      while riding (AOR = 1.96, 95% CI, 1.37-2.85), carrying adults while riding (AOR =
      1.68, 95% CI, 1.23-2.28), riding in the motor lane (AOR = 2.42, 95% CI, 1.05
      3.93), and riding in the wrong traffic direction (AOR = 1.63, 95% CI, 1.13-2.35).
      In over 77.58% of electric bike/moped-related road traffic crashes, riders were
      determined by the police to be responsible for the crash. Major crash-causing
      factors included violating traffic signals or signs, careless riding, speeding,
      and riding in the wrong lane. CONCLUSION: Traffic safety related to electric
      bikes/moped is becoming more problematic with growing popularity compared with
      other 2-wheeled vehicles. Programs need to be developed to prevent electric
      bike/moped-related road traffic injuries in this emerging country.

PMID- 29333876
TI  - Figuring It Out: How Late Adolescent and Young Adult Men and Women Perceive and
      Address Problems in Sexual Functioning.
AB  - Although there are high rates of sexual problems and sexual dysfunction in
      adulthood (Mitchell et al., 2013), little is known about the circumstances under
      which problems are first experienced. A growing body of research addresses
      prevalence of problems in sexual functioning among adolescents and young adults,
      yet little is known about the meanings that young people give to these
      experiences or how they deal with them. We used content analysis of qualitative
      interviews with 53 heterosexual, sexually active Canadian adolescents (ages 18 to
      21) to explore their perceptions of the sexual problems in functioning they had
      experienced and the strategies (if any) they used to address them over time.
      Problems among most young people originated early in their partnered sexual life.
      Figuring it out emerged as an intentional process directed toward improving
      sexual experiences, although certainly not all young people were successful.
      Strategies for figuring it out included informational or material help seeking,
      experimentation to inform future actions, mutual sharing and problem solving, and
      building emotional connection to improve sexual functioning. Implications for
      understanding the development of sexual dysfunctions in adulthood are discussed.

PMID- 29333875
TI  - Ultrafast determination of vitamin E using LC-ESI-MS/MS for preclinical
      development of new nutraceutical formulations.
AB  - AIM: We proposed a rapid and high quality method to determine alpha-tocopherol
      (alpha-T) in different biopharmaceutical samples using liquid chromatography
      diode array detector on-line ESI-MS/MS. MATERIALS & METHODS: A working standard
      solution of alpha-T and internal standard, phenyl-5,7-dimethyl-d6-alpha
      tocopherol, were used for optimization and validation of the method. Levels of
      alpha-T in nanoemulsions, serum and plasma samples were evaluated. RESULTS &
      CONCLUSION: Precision (1% for retention time, 5% for peak area and 3% for
      relative peak area), linearity range (among 0.625-20.0 MUg ml-1), LOD and LOQ,
      accuracy and matrix effect were studied. The validated chromatographic method is
      presented as valuable analytical tool for the determination of alpha-tocopherol
      in loaded drug delivery systems and in biodistribution levels in blood samples.

PMID- 29333877
TI  - What Behaviors Do Young Heterosexual Australians See in Pornography? A Cross
      Sectional Study.
AB  - This study investigated how frequently a group of young heterosexual Australians
      (ages 15 to 29) saw a range of behaviors represented in pornography over the
      previous 12 months. Participants were recruited to an anonymous online survey.
      Those who reported having viewed pornography in the past 12 months (n = 517)
      indicated how frequently they saw each of a list of 17 behaviors when they
      watched pornography in the past 12 months. Men's pleasure (83%) was seen
      frequently by the highest proportion of young people surveyed, followed by a man
      being portrayed as dominant (70%). Women were more likely to report frequently
      seeing violence toward a woman (p < 0.01). Men were more likely to report
      frequently seeing heterosexual anal sex (p < 0.01), ejaculation onto a woman's
      face (p < 0.01), women portrayed as dominant (p < 0.01), a man being called names
      or slurs (p < 0.01), and violence toward a man that appears consensual (p <
      0.01). Younger age was significantly associated with frequently seeing women's
      pleasure (p < 0.05), violence toward women which appeared consensual, and all
      types of violence (p < 0.01). Older age was associated with frequently seeing
      men's pleasure (p < 0.01) and heterosexual anal sex (p < 0.05). Our findings draw
      attention to the gendered ways that behaviors in pornography are seen and
      identified by young heterosexual audiences.

PMID- 29333878
TI  - Glucagon receptor signalling - backwards and forwards.

PMID- 29333879
TI  - Negotiating the Interpretation of Depression Shared Among Kin.
AB  - Kinship processes contribute to the experience and interpretation of depression
      generating empathy as well as silencing. We explore intersubjective experiences
      of depression among kin with the aim of understanding how depression can reveal
      kinship expectations and evolving concepts of distress. In interviews with 28 low
      income rural Appalachian women about their depression, participants articulated
      depression as a social process that neither starts nor ends in themselves. Yet
      kinship obligations to recognize family members' depression limited women's
      ability to admit distress, let alone request care. The intersubjective experience
      of depression among kin can challenge the individual expression of distress.

PMID- 29333881
TI  - Reproductive Travel to Ghana: Testimonies, Transnational Relationships, and
      Stratified Reproduction.
AB  - In this article, I address reproductive travel to Ghana, based on research
      conducted in two private fertility clinics. Both clinics attract clients from
      West African countries as well as Ghanaian people living in the US and Europe.
      Their motivations to visit these clinics include positive "testimonies" about
      treatment results, "bioavailability" of matching donor material and surrogates,
      lower treatment costs and the circumvention of restricting regulations in the
      country of residence. Communication technologies are central in facilitating
      reproductive travel. Finally, I argue that the "international choreographies" of
      reproductive travel are co-shaped by the unique biographies and transnational
      relationships of the people involved.

PMID- 29333882
TI  - Vaginoplasty: What's New From 1946 to Date Commentary on: Vaginoplasty with
      Acellular Dermal Matrix after Radical Resection for Carcinoma of the Uterine
      Cervix.

PMID- 29333880
TI  - Pharmacogenetic analysis of opioid dependence treatment dose and dropout rate.
AB  - BACKGROUND: Currently, no pharmacogenetic tests for selecting an opioid
      dependence pharmacotherapy have been approved by the US Food and Drug
      Administration. OBJECTIVES: Determine the effects of variants in 11 genes on
      dropout rate and dose in patients receiving methadone or buprenorphine/naloxone
      (ClinicalTrials.gov Identifier: NCT00315341). METHODS: Variants in six
      pharmacokinetic genes (CYP1A2, CYP2B6, CYP2C19, CYP2C9, CYP2D6, CYP3A4) and five
      pharmacodynamic genes (HTR2A, OPRM1, ADRA2A, COMT, SLC6A4) were genotyped in
      samples from a 24-week, randomized, open-label trial of methadone and
      buprenorphine/naloxone for the treatment of opioid dependence (n = 764; 68.7%
      male). Genotypes were then used to determine the metabolism phenotype for each
      pharmacokinetic gene. Phenotypes or genotypes for each gene were analyzed for
      association with dropout rate and mean dose. RESULTS: Genotype for 5-HTTLPR in
      the SLC6A4 gene was nominally associated with dropout rate when the methadone and
      buprenorphine/naloxone groups were combined. When the most significant variants
      associated with dropout rate were analyzed using pairwise analyses, SLC6A4 (5
      HTTLPR) and COMT (Val158Met; rs4860) had nominally significant associations with
      dropout rate in methadone patients. None of the genes analyzed in the study was
      associated with mean dose of methadone or buprenorphine/naloxone. CONCLUSIONS:
      This study suggests that functional polymorphisms related to synaptic dopamine or
      serotonin levels may predict dropout rates during methadone treatment. Patients
      with the S/S genotype at 5-HTTLPR in SLC6A4 or the Val/Val genotype at Val158Met
      in COMT may require additional treatment to improve their chances of completing
      addiction treatment. Replication in other methadone patient populations will be
      necessary to ensure the validity of these findings.

PMID- 29333883
TI  - Simultaneous Intestinal and Kidney Transplantation in Adults.
AB  - AIM OF THE STUDY: Intestinal transplantation (IT) is a life-saving procedure for
      carefully selected patients with intestinal failure. We evaluated patients who
      had undergone simultaneous intestinal and kidney transplantation (SIKT) to
      determine whether UK guidelines for inclusion of a renal allograft (dialysis
      dependent or estimated glomerular filtration rate ((eGFR)) < 45 ml/min/1.73 m2)
      are justified. METHODS: A single centre analysis was undertaken of adults
      undergoing IT at the Cambridge Transplant Centre between December 2007 and
      January 2016. A prospectively maintained database was used to identify SIKT
      recipients and determine outcomes. RESULTS: Over this period, 63 intestinal
      transplants were performed. Seven (11.1%) recipients received a SIKT. Five were
      pre-dialysis (median eGFR 29 ml/min/1.73 m2, range 16-36 ml/min/1.73 m2). One
      recipient was on dialysis, and one needed bilateral nephrectomy at transplant.
      There were no primary kidney allograft failures and at three months, the median
      eGFR (55 ml/min/1.73 m2 range 39-124) was similar to recipients of IT alone
      (median eGFR 56 ml/min/1.73 m2 range 17-143 ml/min/1.73 m2). Two recipients
      required dialysis due to sepsis related kidney injury and died from multi-organ
      failure (20 and 63 months). Two died with a functioning renal transplant (10 and
      15 months). The remaining three patients are alive at follow up (12-96 months)
      with an eGFR of 20-45 ml/min/1.73 m2. CONCLUSION: Patients with significant renal
      impairment (eGFR <45 ml/min/1.73 m2), and receiving dialysis may benefit from
      SIKT. Patient survival and renal function are broadly comparable to those
      undergoing IT alone. Further studies are required to justify allocation of a
      kidney to this complex high risk group.

PMID- 29333884
TI  - Use of tidal breathing curves for evaluating expiratory airway obstruction in
      infants.
AB  - OBJECTIVE: To evaluate tidal breathing (TB) flow-volume and flow-time curves for
      identification of expiratory airway obstruction in infants. METHODS: Pulmonary
      function tests were analyzed retrospectively in 156 infants aged 3-24 months with
      persistent or recurrent respiratory complaints. Parameters derived from TB curves
      were compared to maximal expiratory flow at functional residual capacity
      ([Formula: see text]maxFRC) measured by rapid thoracoabdominal compression
      technique. Analyzed parameters were: inspiratory time (tI), expiratory time (tE),
      tidal volume, peak tidal expiratory flow (PTEF), time to peak tidal expiratory
      flow (tPTEF), expiratory flow when 50% and 25% of tidal volume remains in the
      lungs (FEF50, FEF25, respectively), and the ratios tPTEF/tE, tI/tE, FEF50/PTEF,
      and FEF25/PTEF. Statistical comparisons between flow indices and TB parameters
      were performed using mean squared error and Pearson's sample correlation
      coefficient. The study population was also divided into two groups based on
      severity of expiratory obstruction (above or below z-score for [Formula: see
      text]maxFRC of -2) to generate receiver operating characteristic (ROC) curves and
      calculate discriminatory values between the groups. RESULTS: TB parameters that
      were best correlated to [Formula: see text]maxFRC were: tPTEF/tE, FEF50/PTEF, and
      FEF25/PTEF, with r = 0.61, 0.67, 0.65, respectively (p < 0.0001 for all). ROC
      curves for FEF50/PTEF, FEF25/PTEF and tPTEF/tE showed areas under the curve of
      0.813, 0.797, and 0.796, respectively. Cutoff value z-scores of -0.35, -0.34, and
      -0.43 for these three parameters, respectively, showed an 86% negative predictive
      value for severe airway obstructions. CONCLUSION: TB curves can assist in ruling
      out severe expiratory airway obstruction in infants.

PMID- 29333885
TI  - When biomarkers define a drug indication.

PMID- 29333887
TI  - Physical and Psychological Abuse among Seropositive African American MSM 50 Aged
      Years and Older.
AB  - Little is known about abuse experienced among African American men who have sex
      with men (MSM) who are 50 years and older. A series of focus groups were
      conducted to examine perspectives of seropositive African American MSM age 50
      years and older who reported experiencing some form of psychological or physical
      abuse. Thirty African American MSM were divided into four focus groups and four
      themes emerged: "Fear Being Gay," "No One Else to Love Me," "Nowhere to Turn,"
      and "Sexual Risk & Control." The data suggest there is a need to develop
      culturally tailored interventions for this population.

PMID- 29333886
TI  - Anaemia worsens early functional outcome after traumatic brain injury: a
      preliminary study.
AB  - OBJECTIVE: To determine early effects on outcome from traumatic brain injury
      (TBI) induced by controlled cortical impact (CCI) associated with anaemia in
      mice. HYPOTHESIS: Outcome from TBI with concomitant anaemia would be worse than
      TBI without anaemia. METHODS: CCI was induced with electromagnetic impaction in
      four groups of C57BL/6J mice: sham, sham+anaemia; TBI; and TBI+anaemia. Anaemia
      was created by withdrawal of 30% of calculated intravascular blood volume and
      saline replacement of equal volume. Functional outcome was assessed by beam
      walking test and open field test (after pre-injury training) on post-injury days
      3 and 7. After functional assessment, brains removed from sacrificed animals were
      pathological reviewed with haematoxylin and eosin, cresyl violet, Luxol Fast
      Blue, and IBA-1 immunostains. RESULTS: Beam-walking was similar between animals
      with TBI and TBI+anaemia (p = 0.9). In open field test, animals with TBI+anaemia
      walked less distance than TBI alone or sham animals on days 3 (p < 0.001) and 7
      (p < 0.05), indicating less exploratory and locomotion behaviours. No specific
      pathologic differences could be identified. CONCLUSIONS: Anaemia associated with
      TBI from CCI is associated with worse outcome as measured by less distance
      travelled in the open field test at three days than if anaemia is not present.

PMID- 29333888
TI  - Primary Diffuse Large B-Cell Lymphoma of the Ciliary Body.
AB  - PURPOSE: To report an unusual case of an eye with primary ciliary body lymphoma
      which came to enucleation allowing detailed histopathological examination.
      METHODS: A 50-year-old man presented with a painful loss of vision in the left
      eye. The clinical, imaging, and immunohistopathological features of this case
      were reviewed. RESULTS: The vision in the left eye was light perception. There
      were keratic precipitates, an irregular and thickened iris with
      neovascularization. Imaging studies disclosed a ciliary body mass extending into
      the anterior chamber. The eye was enucleated and immunohistopathological
      examination showed positive staining with CD20, BCL-2, MUM1, and CD10. Staining
      with BCL-6 was weak and S100 and HMB45 expressions were negative. Occasional CD3+
      reactive T cells were present. The Ki-67 index was 80-90%. All these results
      suggested diffuse large B-cell lymphoma. CONCLUSIONS: Diffuse large B-cell
      lymphoma may primarily arise from the ciliary body and can develop without
      systemic or central nervous system disease.

PMID- 29333889
TI  - Risking It Anyway: An Adolescent Case Study of Trauma, Sexual and Gender
      Identities, and Relationality.
AB  - This article presents the case of a Chinese-American adolescent with a
      significant trauma history who was questioning her sexual and gender identities.
      The implications of the client's intersecting identities for case
      conceptualization and treatment are considered within the framework of
      affirmative practices for sexual and gender minority (SGM) clients. The impacts
      of stress and trauma on this client's experiences-and SGM clients more broadly
      are also considered, particularly with respect to how this client understood and
      negotiated her experiences of relational trauma. This case is intended to
      illustrate some best practices with SGM clients within an intersectional
      framework which underscores the importance of multiple salient cultural
      identities.

PMID- 29333891
TI  - Therapeutic Potential of Zataria multiflora Boiss in Treatment of Irritable Bowel
      Syndrome (IBS).
AB  - Irritable Bowel syndrome (IBS), the most common chronic functional
      gastrointestinal disorder, is categorized as IBS-C and IBS-D, which are
      equivalent to Ghoolenj Rihi and Maghs Rihi in Iranian traditional medicine. One
      of the main applications of Zataria multiflora Boiss in traditional medicine is
      its efficacy in the gastrointestinal tract with symptoms such as IBS. The aim of
      this study was to evaluate the efficacy of Zataria multiflora essential oil in
      management of IBS. We used all the accessible references (electronic and
      published books, theses, and reports) to write this article. The results of our
      investigation show that the majority of gas chromatography-mass spectrometry (GC
      MS) analyses exhibited carvacrol and thymol as the main components of Zataria
      multiflora essential oil, and 60 drops oral daily dose of Z. multiflora essential
      oil (2%) can relieve the symptoms of IBS without any adverse effects. The
      pharmacological studies confirmed the analgesic, anti-inflammatory, antispasm and
      antiulcer effects of Z. multiflora essential oils and main components. According
      to the results of studies, oral Z. multiflora essential oil (2%) is a good
      candidate for management of IBS, but more studies are required to better
      understand its efficacies.

PMID- 29333890
TI  - Cigarette smoking and quit attempts among Latinos in substance use disorder
      treatment.
AB  - BACKGROUND: Differences in tobacco use behaviors have been identified between
      Latinos and non-Latino whites in the general US population. Little is known about
      cigarette smoking and quitting behaviors of Latinos in treatment for substance
      use disorders (SUDs), who represent two major tobacco-vulnerable groups.
      OBJECTIVES: To compare, in a national sample of persons enrolled in SUD
      treatment, demographic, drug use, and smoking and quitting prevalence and
      behaviors between Latinos and non-Latino whites. METHODS: We surveyed 777 SUD
      treatment clients, sampled from 24 clinics selected at random from the National
      Institute on Drug Abuse Clinical Trials Network (Latino client n = 141; 40%
      female). We then conducted univariate and multivariate analyses to identify
      correlates of smoking behaviors by Latino/non-Latino white ethnicity. RESULTS:
      Latinos' smoking prevalence resembled that of non-Latino whites (78.7% vs.
      77.4%). In regression analyses, Latino smokers (n = 111) tended to smoke fewer
      cigarettes per day (CPD) than non-Latino white smokers (n = 492); were more often
      nondaily smokers and menthol smokers; more often reported a smoking quit attempt
      in the last year; and tended to report higher numbers of past-year quit attempts.
      Among Latino smokers, those with less education and those reporting opioids as
      their primary drug of use reported higher CPD. CONCLUSIONS: Latinos in SUD
      treatment are at equally high risk of being current heavy smokers as compared to
      non-Latino whites in SUD treatment. At the same time, Latinos in SUD treatment
      exhibit ethnic-specific smoking and quitting behaviors that should be considered
      when designing smoking interventions for this group.

PMID- 29333892
TI  - Education Needs of Families of Transgender Young People: A Narrative Review of
      International Literature.
AB  - Education plays a crucial role in the lives of families of transgender young
      people and mental healthcare practitioners are well-placed to support families in
      this regard. This paper reports findings from a narrative review of 31 papers
      that explored the education needs of families of transgender young people. The
      emergent themes were synthesised to develop a five-stage model that depicts the
      role of education in the lives of these families. Key themes included: (i)
      learning that a family member is trans; (ii) family responses; (iii) accessing
      education and information; (iv) impact on the individual; and (iv) moving beyond
      the individual. The key implications for mental health practitioners, families,
      and future research are discussed.

PMID- 29333893
TI  - Syringe Administration of Epinephrine by Emergency Medical Technicians for
      Anaphylaxis.
AB  - OBJECTIVE: In recent years, the costs of epinephrine autoinjectors (EAIs) in the
      United States have risen substantially. King County Emergency Medical Services
      implemented the "Check and Inject" program to replace EAIs by teaching emergency
      medical technicians (EMTs) to manually aspirate epinephrine from a single-use 1
      mg/mL epinephrine vial using a needle and syringe followed by prehospital
      intramuscular administration of the correct adult or pediatric dose of
      epinephrine for anaphylaxis or serious allergic reaction. Treatment was guided by
      an EMT protocol that required a trigger and symptoms. We sought to determine if
      the "Check and Inject" program was safely implemented by EMTs treating presumed
      prehospital anaphylaxis or serious allergic reaction. METHODS: We conducted a
      prospective investigation of all cases treated as part of the "Check and Inject"
      program from July 2014 through December 2016 in suburban King County, Washington,
      and January 2016 through December 2016 within the city of Seattle. All cases were
      prospectively collected using a custom quality improvement data form completed by
      the first responding EMTs. Two physicians completed a structured review of each
      EMS medical record to determine if the EMTs followed the Check and Inject
      protocol and determine if epinephrine was clinically-indicated based on physician
      review. RESULTS: Of the 411 cases eligible for analysis, EMTs followed the
      protocol appropriately in 367 (89.3%) cases. In the remaining 44 (10.7%) cases,
      the EMS incident report form failed to document either a clear inciting allergic
      trigger or an appropriate symptom from the protocol list. Physician review
      determined that epinephrine was clinically indicated in 36 of the 44 cases. Among
      the remaining 8 cases (1.9%) that did not meet protocol criteria and were not
      clinically-indicated based on physician review, none had a documented adverse
      reaction to the epinephrine. CONCLUSION: We observed that EMTs successfully
      implemented the manual "Check and Inject" program for severe allergic reactions
      and anaphylaxis in a manner that typically agreed with physician review and
      without any overt identified safety issues.

PMID- 29333895
TI  - Childhood Adversity and Hazardous Drinking: The Mediating Role of Attachment
      Insecurity.
AB  - BACKGROUND: Harmful alcohol use is associated with disease and mortality.
      Identifying new determinants of harmful drinking may aid the 16.3 million adults
      who have alcohol use disorders. Childhood adversity is associated with alcohol
      use, but is not amenable to change. Attachment insecurity (anxiety and avoidance)
      may be associated with alcohol use and may be a target for modification or used
      to personalize interventions. OBJECTIVES: This study aims to (a) identify the
      association between attachment insecurity and harmful drinking, (b) determine if
      attachment insecurity may mediate between childhood adversity and harmful
      drinking, and (c) test sex as a moderator between attachment insecurity and
      harmful drinking in the mediation relationship. METHODS: Adult primary care
      patients (N = 348, 60% women) completed a cross-sectional survey study using
      validated measures in 2012. Statistical analyses were performed using Hayes's
      PROCESS macro in SPSS. RESULTS: Childhood adversity was reported by 61% of the
      cohort and 18% endorsed harmful drinking. Attachment anxiety was associated with
      harmful drinking (p >.001), but attachment avoidance was not (p =.11). Attachment
      anxiety may mediate between childhood adversity and harmful drinking (95% CI:.03
      .14). Sex did not moderate the relationships between attachment anxiety and
      harmful drinking in the mediation relationship (women: 95% CI:.031-.179; men: 95%
      CI:.003.-.182). Conclusions/Importance: Attachment anxiety may mediate between
      childhood adversity and harmful drinking in both men and women. Attachment
      anxiety may be a potential therapeutic target for people with a history of
      childhood adversity.

PMID- 29333896
TI  - Cataract Surgery in HIV Seropositive Patients: Long-Term Follow-Up.
AB  - PURPOSE: To study epidemiology and clinical findings of cataract in HIV+
      patients. METHODS: A total of 32 HIV+ patients, 11 with uveitis/retinitis before
      surgery and 21 without, mean follow-up 44.9 +/- 36.6 months, and 114 HIV-
      patients, 57 with uveitis/retinitis before surgery and 57 without, were
      retrospectively compared. RESULTS: Visual acuity improved in all HIV+ patients (p
      < 0.001), who were younger (p = 0.01) and more frequently males (p = 0.027). HIV+
      patients with uveitis prior surgery improved less (p = 0.046) than HIV- (p <
      0.001); their anterior chamber inflammation was similar to baseline. Male sex (p
      = 0.005), younger age (p < 0.001), dyslipidaemia (p = 0.058), HBV+ (p = 0.037),
      and unilateral cataract (p = 0.001) were more frequent in HIV+ patients with
      senile cataract, but they showed the same postoperative course as HIV- patients.
      CONCLUSION: Cataract surgery in HIV+ patients is safe and effective. Uveitis
      prior to surgery did not significantly affect the postoperative course. Systemic
      comorbidities are more frequent in HIV+ patients with senile cataract than in HIV
      subjects.

PMID- 29333897
TI  - Adherence to the American Diabetes Association retinal screening guidelines for
      population with diabetes in the United States.
AB  - PURPOSE: (1) To assess long-term adherence to American Diabetes Association
      guideline-recommended retinal screening among population with diabetes in the
      United States. (2) To determine factors associated with long-term adherence to
      routine eye screening exams. METHODS: A retrospective cohort study was conducted
      in adult patients with diabetes identified from January 2009 to December 2010.
      Patients were followed until disenrollment, death, or study end date (December
      2013). A patient was defined as adherent when having at least one exam in each 12
      month period if there was evidence of retinopathy, or at least one exam in each
      24-month period if there was no evidence of retinopathy. Multivariate logistic
      regressions were used to investigate patient demographics and other baseline
      characteristics associated with adherence to guidelines. RESULTS: A total of
      204,073 patients were identified; the mean age (SD) was 61 (13) years and 48%
      were female. Overall, 71.1% were adherent to the retinal screening guidelines
      during a median of 4.8 years of follow-up including 27.7% who received an eye
      exam every year. Patient socioeconomic status (younger age, black race, lower
      income/education), less comorbidity, insulin use, higher specialist copayment
      plans, and proxies for poor patient behavior (lower adherence to the oral
      hypoglycemic agents, less diabetes education, hemoglobin A1C >9%) were associated
      with nonadherence to routine eye screening exams. CONCLUSION: During nearly 5
      years of follow-up, 28.9% of patients with diabetes were nonadherent to the
      retinal screening guidelines. Future research should focus on the development of
      interventions to address modifiable factors associated with nonadherence.

PMID- 29333898
TI  - The Physical Health of Individuals Receiving Antipsychotic Medication: A
      Qualitative Inquiry on Experiences and Needs.
AB  - Individuals with a mental illness are reported to have a reduced life expectancy
      and a greater risk of being affected by preventable physical illnesses such as
      cardiovascular disease and Type 2 diabetes. This inquiry sought to identify the
      physical health beliefs, experiences and needs of individuals with mental health
      problems in receipt of antipsychotic medication who live in the community. A
      qualitative inquiry was undertaken using three focus groups in a community mental
      health service in Ireland with 21 participants with mental health problems who
      were treated with antipsychotic medication. The participants were clear about the
      importance of good physical health as well as good mental health. They disliked
      the adverse effects of antipsychotic medication and experienced many barriers in
      accessing general practitioners/primary care services. They also preferred to
      receive health advice and self-management advice from the mental health services.
      The participants in this study were aware of the need to engage in health
      protective behaviours but were often overwhelmed by their comorbid health issues
      and the organizational and communication barriers in accessing their general
      practitioners.

PMID- 29333899
TI  - Social Support and Mental Health in LGBTQ Adolescents: A review of the
      literature.
AB  - LGBTQ adolescents experience higher rates of mental health disorders than their
      heterosexual peers. The purpose of this systematic review of the literature was
      to examine studies evaluating social support and its effects on mental health in
      the LGBTQ adolescent population. Higher levels of social support were associated
      with positive self-esteem. Lack of social support (or low social support) was
      associated with higher levels of depression, anxiety, alcohol or drug misuse,
      risky sexual behaviors, shame, and low self-esteem. Interdisciplinary research
      teams from multiple and diverse professions could provide valuable insight
      supporting the development of inclusive and comprehensive interventions programs
      for this population.

PMID- 29333900
TI  - Stability of two anterior fixations for three-column injury in the lower cervical
      spine: biomechanical evaluation of anterior pedicle screw-plate fixation.
AB  - Objectives This study aimed to evaluate the stability of anterior pedicle screw
      plate (APSP) fixation and anterior vertebral body screw-plate (AVBSP) fixation
      for three-column injury in the lower cervical spine. Methods Six fresh-frozen
      human cadaveric specimens of the lower cervical spine were prepared. After
      measurement of the range of motion (ROM) in the intact state, the specimens were
      prepared as three-column injury models. The models were stabilized by AVBSP or
      APSP fixation. The ROM of the models in the two states was measured. The ROM in
      the two states was compared. Results The ROM of the intact state in all
      directions was significantly smaller than that of the AVBSP state and
      significantly larger than that of the APSP state. The ROM of the AVBSP state in
      all directions was significantly larger than that of the APSP state. Conclusions
      This study shows that APSP fixation can provide sufficient stability for three
      column injury in the lower cervical spine. The primary stability of our models
      using APSP fixation is superior to that of AVBSP fixation. These results suggest
      that APSP can be used for three-column injury in the lower cervical spine.

PMID- 29333901
TI  - HER2 positive bilateral metachronous primary breast carcinoma: A case report.
AB  - Human epidermal growth factor receptor 2 (HER2) positive is a unique molecular
      subtype of breast cancer (BC) characterized by high malignancy and poor
      prognosis. Bilateral primary breast cancer (BPBC) harboring HER2 gene
      amplification is available to be detected among the BC survivors due to the
      increasing use of anti-HER2 adjuvant therapy. However, owing to the paucity of
      cases reported, knowledge of treating HER2-positive BPBC patients including the
      clinical behavior, histopathologic characteristics, anti-HER2 therapeutic
      response and disease outcome are not fully understood. Here we report a case of
      its kind receiving nonstandardized treatment during adjuvant stage. Upon tumor
      recurrence with liver metastasis, she received trastuzumab combined with
      chemotherapy and reached a PFS of 14.5 months in first-line treatment. While
      maintained trastuzumab plus carboplatin as second-line treatment progressed
      promptly, re-treatment of trastuzumab after lapatinib administration in third
      line can still benefit the patient. The present case report delineates an anti
      HER2 path for a particular characterized patient, and also provides new evidence
      of trastuzumab re-usage after disease progression of prior anti-HER2 therapy.

PMID- 29333902
TI  - Patterns of NPS Use and Risk Reduction in Slovenia.
AB  - BACKGROUND: The following study presents factors influencing the decision to
      use/not to use new psychoactive substances (NPS), various patterns of NPS use,
      the problems experienced by users, and the methods for reducing the risks
      associated with NPS use. OBJECTIVES: The study seeks to provide an in-depth look
      into the characteristics of NPS use and support the planning of targeted
      interventions in the field of NPS. METHODS: The study involved 19 in-depth
      interviews carried out with 25 individuals divided into three subsamples in order
      to gain insight into the various experiences of NPS users. The interviews were
      conducted in Slovenia between December 2013 and October 2014. The sample was
      obtained by using the convenience sampling and snowball sampling methods.
      RESULTS: The main pattern of NPS use determined by the study concerned synthetic
      cathinones, specifically 3-MMC, with binge use spanning several days being a
      prominent feature. The main risks involving NPS use were: mixing various drugs,
      inappropriate dosing, lack of information prior to use, and the use of unknown
      substances. Several users spoke about effective strategies for reducing risks,
      such as obtaining information beforehand, using one's own implements and using
      only small quantities of unknown substances. Conclusions/Importance: The study
      revealed various factors based on which users decide to use NPS. Furthermore,
      users reported a number of problems resulting from NPS use, while risk reduction
      strategies are employed to a much lesser extent. Based on the results obtained,
      specific intervention efforts concerning NPS use and targeting specific groups of
      younger users were designed.

PMID- 29333903
TI  - The First Report of Relative Incidence of Inherited White Matter Disorders in an
      Asian Country Based on an Iranian Bioregistry System.
AB  - Childhood leukodystrophies are a fast-growing field of pediatric neurology
      practice. Epidemiologic studies on the incidence of these disorders in children
      show different results. This is the first report of childhood leukodystrophies
      incidence from Iran. The enrolled patients were recruited from the neurometabolic
      bioregistry system that was organized in 2010 in the Children's Medical Center,
      Tehran, Iran. Herein is reported the incidence rate of leukodystrophies in those
      patients who were residents of 2 big popular provinces near Iran's capital city
      Tehran, with an average child population of 2 988 800 children. Ninety cases of
      leukodystrophies from Tehran and Alborz provinces who were registered between
      2010 and 2016 in the bioregistry system were enrolled in this study. The annual
      incidence of inherited white matter disorders was 3.01/100 000, the highest
      number compared with those found in other studies using similar methods
      throughout the world. One of the main cause of this higher incidence could be the
      higher number of consanguineous marriages in Iran.

PMID- 29333904
TI  - The biological treatment planning evolution of clinical fractionated radiotherapy
      using high LET.
AB  - Starting from the birth of high linear energy transfer (LET) radiotherapy in USA
      in the mid-1970s, the field has continuously evolved and to date over 20,000
      patients have been treated with 12C ions worldwide. The purpose of this
      contribution is to review the advancements in clinical fractionated radiotherapy
      using high LET radiation in the last decades, with special focus on biological
      treatment planning. Along with technological developments for ion acceleration
      and beam delivery, progress in radiation biology and computational modeling has
      enabled a remarkable evolution in the planning capabilities of highly conformal,
      biologically optimized treatment with high LET radiation. In particular, recent
      efforts have provided the possibility of direct comparison between treatment
      plans obtained at different facilities with different biological models for the
      same ion species. This achievement represents an important step forward to gather
      better understanding of the remaining uncertainties in biological modeling and
      the impact of fractionation for optimal dose prescriptions, ultimately aiming to
      promote clinical exploitation of the anticipated, yet not fully demonstrated
      advantages of high LET-charged particles.

PMID- 29333905
TI  - Linear nevus sebaceous syndrome presenting as circumscribed choroidal hemangioma.
AB  - A 4-year-old female with a unilateral circumscribed choroidal hemangioma and
      secondary total exudative retinal detachment. A nasal skin scar-like lesion
      incised to confirm a histopathologic diagnosis of linear nevus sebaceous. Further
      imaging disclosed asymmetry of the lateral ventricle frontal horns, suggestive of
      the diagnosis of linear nevus sebaceous syndrome. The choroidal hemangioma was
      treated with I-125 episcleral brachytherapy (apical dose of 45 Gy). At 6 months
      post-radiation, the tumor showed regression with total resolution of exudative
      retinal detachment.

PMID- 29333906
TI  - TUBB1 variants and human platelet traits.

PMID- 29333907
TI  - Quantitative methods in interprofessional education research: some critical
      reflections and ideas to improving rigor.

PMID- 29333908
TI  - False positive acetylcholine receptor antibodies in a case of unilateral chronic
      progressive external ophthalmoplegia: case report and review of literature.
AB  - METHODS: We present a rare case with atypical presenting features of unilateral
      CPEO with a false positive Acetylcholine Receptor Antibody (AchRA) test resulting
      in diagnostic delay. We illustrate the unilateral nature of this case and
      demonstrate the caveats of performing myogenic ptosis correction in such
      patients. We also discuss the differential diagnosis of false positive AchRA, a
      test commonly performed in the investigation of ptosis. RESULTS: A 34-year old
      female presented with a more than 3-year history of slowly-progressive,
      unilateral, right-sided restriction in eye movements and ptosis. Clinical
      examination showed EOM were grossly restricted in the right eye with a ptosis and
      normal in the left eye. Serum AchRA was positive on serum enzyme-linked
      immunosorbent assay (ELISA) however, following two months of oral pyridostigmine
      therapy there were no signs of clinical improvement. The initial serum sample
      sent was retested for AchRA by radio-immunoassay (RIA) which came back negative.
      Subsequently a muscle biopsy was requested which showed the presence of ragged
      red fibres. CONCLUSION: Unilateral ptosis and ophthalmoplegia is an unusual
      presentation for CPEO which characteristically produces bilateral symmetrical
      motility defects. In addition to Myasthenia Gravis elevated AchRA levels have
      been reported in other autoimmune conditions such as Primary biliary cirrhosis,
      Eaton Lambert syndrome and Graves's ophthalmopathy. We also highlight the
      superiority of RIA versus ELISA in the detection of AchRA and illustrate the
      diagnostic challenge of investigating and managing myogenic ptosis in this
      complex cohort of patients.

PMID- 29333909
TI  - Subclinical Inflammatory Response: Accelerated versus Standard Corneal Cross
      Linking.
AB  - PURPOSE: To compare the subclinical inflammatory response (as measured by
      anterior chamber flare) induced after standard (3 mW/cm2, 30 min) and accelerated
      (18 mW/cm2, 5 min) corneal cross-linking (CXL). METHODS: In this comparative, non
      randomized study, patients with progressive keratoconus who underwent standard or
      accelerated CXL were studied. Laser flare photometery (FM-600; Kowa, Tokyo,
      Japan) was used to measure anterior chamber flare preoperatively and at 1 week, 1
      month, 3 months, and 6 months after the procedure. RESULTS: Sixty eyes of 60
      patients were studied; 30 eyes in each group. Mean baseline flare values were
      4.15 +/- 1.19 and 4.57 +/- 2.17 ph/ms in standard and accelerated groups,
      respectively (p = 0.228).and after surgery increased in all follow-up
      measurements in the both groups similarly (P > 0.05). CONCLUSION: Both standard
      and accelerated CXL results in induction of a subclinical inflammatory response
      that persists up to 6 month. The response was similar between the two groups.

PMID- 29333910
TI  - Soft Contact Lenses to Optimize Vision in Adults with Idiopathic Infantile
      Nystagmus: A Pilot Parallel Randomized Controlled Trial.
AB  - PURPOSE: The optimal management of infantile nystagmus syndrome (INS) is still
      unclear. Contact lenses (CL) may be superior to glasses in improving visual
      function in INS but it is not known whether their beneficial effects are due to
      optical correction alone, or to an additional proprioceptive effect, and whether
      soft CLs would be as effective as rigid CLs. There is little data on feasibility
      and and the present study aimed to provide this information. METHODS: We
      completed a pilot Randomized Control Trial (RCT) at a single tertiary referral
      centre in London, UK. We enrolled 38 adults with idiopathic INS and randomised
      them to either plano CL (with corrective spectacles if required) or to corrective
      CL. CL wear was required for a minimum of 2 weeks. Primary outcome measures were
      feasibility and safety of CL wear in INS; secondary outcome measures were visual
      acuity and nystagmus waveform parameters. RESULTS: 27 completed the study
      (27/38,71%). 4 partcipants withdrew due to difficulty with CL insertion/removal
      and 7 were lost to follow up. CL tolerability was high (24/27,89%) - 2 found the
      CLs irritant, and 1 had an exacerbation of allergic eye disease. At two weeks,
      mean improvement in binocular visual acuity from baseline with plano CLs was 0.07
      logMAR (95% confidence interval (CI: 0.03-0.11) and 0.06 logMAR with fully
      corrective CLs (95% CI:0.02-0.1). Mean improvement in the eXpanded Nystagmus
      Acuity Function (NAFX, a nystagmus acuity function based on eye movement
      recording) with plano CLs was -0.04(95% CI: -0.08-0.005) and -0.05 with fully
      corrective CLs(95% CI: -0.09-0.003). CONCLUSIONS: CLs are well tolerated, with a
      low risk profile. Whilst our study was not powered to detect significant changes
      in BCVA and waveform parameters between treatment arms, we observed a trend
      towards an improvement in visual function at two weeks from baseline with CLs.

PMID- 29333911
TI  - The Challenge of Pediatric Uveitis: Tertiary Referral Center Experience in the
      United States.
AB  - PURPOSE: To describe the distribution, clinical findings, visual outcomes,
      treatment, and complications of children with uveitis at a tertiary referral
      ophthalmic center. METHODS: Retrospective cohort study. We reviewed the medical
      records of all patients <=16 years with uveitis referred to Massachusetts Eye
      Research and Surgery Institution from March 2005 to July 2016. RESULTS: Of 286
      included children, 62.24% were female. Mean age of onset was 8.4 years. The
      uveitis was mainly anterior (61.9%), recurrent (68.53%), bilateral (81.82%), and
      noninfectious (96.5%). Idiopathic cases accounted for 51.4%. The most frequent
      systemic association was juvenile idiopathic arthritis (34.96%). The majority of
      patients (78.32%) experienced complications. All patients, except one, needed
      systemic therapy. CONCLUSION: Pediatric uveitis is challenging to diagnose and
      manage, with frequent and potentially severe complications. Most cases were
      bilateral, recurrent, and idiopathic. Prompt referral to uveitis-specialized
      centers and an appropriate systemic therapy are mandatory for good visual
      outcomes.

PMID- 29333912
TI  - The resting-state fMRI arterial signal predicts differential blood transit time
      through the brain.
AB  - Previous studies have found that aperiodic, systemic low-frequency oscillations
      (sLFOs) are present in blood-oxygen-level-dependent (BOLD) data. These signals
      are in the same low frequency band as the "resting state" signal; however, they
      are distinct signals which represent non-neuronal, physiological oscillations.
      The same sLFOs are found in the periphery (i.e. finger tips) as changes in
      oxy/deoxy-hemoglobin concentration using concurrent near-infrared spectroscopy.
      Together, this evidence points toward an extra-cerebral origin of these sLFOs. If
      this is the case, it is expected that these sLFO signals would be found in the
      carotid arteries with time delays that precede the signals found in the brain. To
      test this hypothesis, we employed the publicly available MyConnectome dataset (a
      two-year longitudinal study of a single subject) to extract the sLFOs in the
      internal carotid arteries (ICAs) with the help of the T1/T2-weighted images.
      Significant, but negative, correlations were found between the LFO BOLD signals
      from the ICAs and (1) the global signal (GS), (2) the superior sagittal sinus,
      and (3) the jugulars. We found the consistent time delays between the sLFO
      signals from ICAs, GS and veins which coincide with the blood transit time
      through the cerebral vascular tree.

PMID- 29333913
TI  - Boxing fatalities in relation to rule changes in Japan: secondary data analysis.
AB  - OBJECTIVES: To examine whether changing weigh-in from the same day of the match
      to the day before the match and prohibiting 6-oz gloves are associated with
      fatalities in boxing matches sanctioned by the Japan Boxing Commission (JBC).
      METHODS: We analyzed the rates of boxing fatalities before and after the two rule
      changes above via secondary analysis of data. Demographics and boxing records of
      deceased boxers were examined using descriptive statistics, exact binomial test
      the Mann-Whitney-Wilcoxon test and Fisher's exact tests. RESULTS: As of this
      study, a total of 38 boxers (23.9 +/- 3.3 years of age) reportedly died due to
      injuries sustained in JBC-sanctioned boxing matches since 1952. Changing weigh-in
      to the day before the match or prohibiting 6-oz gloves was not significantly
      associated with the rates of boxing fatalities 5 years and 10 years before and
      after the rule changes (p > 0.05). Deceased boxers after these rule changes were
      significantly older, completed significantly more rounds in the final match, and
      were significantly less likely to lose the previous match (prior to the final
      match) and to do so by knockouts (p < 0.05). CONCLUSION: Changing weigh-in to the
      day before the match and prohibiting 6-oz gloves may not result in reducing
      boxing fatalities.

PMID- 29333914
TI  - Hybrid PET/MRI imaging in healthy unsedated newborn infants with quantitative
      rCBF measurements using 15O-water PET.
AB  - In this study, a new hybrid PET/MRI method for quantitative regional cerebral
      blood flow (rCBF) measurements in healthy newborn infants was assessed and the
      low values of rCBF in white matter previously obtained by arterial spin labeling
      (ASL) were tested. Four healthy full-term newborn subjects were scanned in a
      PET/MRI scanner during natural sleep after median intravenous injection of 14 MBq
      15O-water. Regional CBF was quantified using a one-tissue-compartment model
      employing an image-derived input function (IDIF) from the left ventricle. PET
      rCBF showed the highest values in the thalami, mesencephalon and brain stem and
      the lowest in cortex and unmyelinated white matter. The average global CBF was
      17.8 ml/100 g/min. The average frontal and occipital unmyelinated white matter
      CBF was 10.3 ml/100 g/min and average thalamic CBF 31.3 ml/100 g/min. The average
      white matter/thalamic ratio CBF was 0.36, significantly higher than previous ASL
      data. The rCBF ASL measurements were all unsuccessful primarily owing to subject
      movement. In this study, we demonstrated for the first time, a minimally invasive
      PET/MRI method using low activity 15O-water PET for quantitative rCBF assessment
      in unsedated healthy newborn infants and found a white/grey matter CBF ratio
      similar to that of the adult human brain.

PMID- 29333915
TI  - Gaze avoidance and perseverative language in fragile X syndrome and autism
      spectrum disorder: brief report.
AB  - Gaze avoidance and perseverative language impact pragmatics in autism spectrum
      disorder (ASD) and fragile X syndrome (FXS). We examined these features during
      conversation samples in boys with ASD (n = 10) and boys with FXS and ASD
      (FXS+ASD; n = 10). Both groups had similar high rates of gaze avoidance and topic
      and conversation device perseverations, yet these features were not correlated
      with one another. Boys with FXS+ASD produced a higher proportion of single
      utterance perseverations. Results from this study highlight the need for future
      research to identify potential mechanisms influencing the presence of language
      perseverations and gaze avoidance.

PMID- 29333917
TI  - Role of cortical microbleeds in cognitive impairment: In vivo behavioral and
      imaging characterization of a novel murine model.
AB  - Cerebral microbleeds (CMBs) could contribute to cognitive impairment in the
      general population and in patients with dementia. We designed a study to (i)
      develop a murine model of CMBs, (ii) assess whether CMBs affect cognition in this
      model and (iii) assess whether this model is sensitive to pharmacological
      modulation. Male C57Bl6/J mice were stereotactically administered collagenase to
      induce cortical lesion analysed by MRI at 24 h. CMB-mice were assessed at six
      weeks post-lesion for cognitive performances (Barnes maze and Touchscreen
      automated paired-associated learning (PAL) task) and for cerebral metabolism (in
      vivo PET/CT with fluorodeoxyglucose (FDG)). CMB-model sensitivity to
      pharmacological modulation was assessed by administering atorvastatin (5
      mg/kg/day) over the follow-up period. CMB mice were compared to naive
      littermates. Collagenase at 0.8 uU/ul appeared suitable to induce reproducible
      and reliable CMBs. At six weeks, a decline in learning, spatial and visuospatial
      memory was significantly observed in CMB-mice. Brain metabolism was impaired in
      all cortex, striatum and the ipsilateral dentate gyrus. A significant improvement
      in cognition performances was depicted under atorvastatin. In this novel murine
      model of CMBs, we validated that CMBs lowered cognitive performances and affected
      regional metabolism. We also proved that this CMB-model is sensitive to
      pharmacological modulation.

PMID- 29333918
TI  - Modified second stage Hughes tarsoconjunctival reconstruction for lower eyelid
      defects.
AB  - To describe a novel technique utilizing an amniotic membrane graft (AMT) to
      create the mucocutaneous portion of the lower eyelid margin in a modified Hughes
      eyelid reconstruction for secondary revision or prevention of a hyperemic,
      hypertrophic conjunctival margin with excessive discharge. This was a
      retrospective, non-comparative interventional study. Thirty consecutive patients
      who underwent a modified Hughes reconstruction were included. The first step of
      the reconstruction was performed in a standard fashion using a tarsoconjunctival
      flap from the ipsilateral upper eyelid. The second stage was accomplished by the
      division of the tarsoconjunctival flap. The modification of the procedure
      included the addition of AMT (Ambio 5(r), IOP Ophthalmics, CA) to the new
      mucocutaneous junction. Main outcome measures included the post Mohs surgery
      defect size, post-reconstruction complications. One patient received AMT for a
      revision of a hyperemic lid margin following reconstruction, while 29 subsequent
      patients received AMT as a primary procedure. The mean size of the post-Mohs
      defect was 23.75 +/- 6.6 mm2 horizontally and 9.1 +/- 5.4 mm2 vertically,
      involving 79.53 +/- 16.8% of the lower eyelid. There was no evidence of hyperemic
      or hypertrophic margin at a mean follow-up of 4.41 +/- 2.91 months. The addition
      of an AMT for the revision, or as a primary procedure for prevention of a
      hyperemic, hypertrophic eyelid margin with excess mucus production in the post
      Hughes lower eyelid reconstruction has favorable outcomes in this preliminary
      study, however warrants further investigation with larger number of patients and
      longer follow-up.

PMID- 29333916
TI  - Cytoplasmic collagen XIalphaI as a prognostic biomarker in esophageal squamous
      cell carcinoma.
AB  - Stromal/cytoplasmic collagen XIalphaI (COL11A1) has been highlighted in the
      process of neoplastic transformation, including epithelial mesenchymal transition
      (EMT), metastasis and invasiveness. In this study, we aim to illuminate the
      clinical significance and biological role of COL11A1 in esophageal squamous cell
      carcinoma (ESCC). Herein, we investigated COL11A1 expression in 16 pairs of ESCC
      and adjacent normal tissues by RT-PCR and western blotting analysis. Correlations
      of COL11A1 expression with clinicopathologic parameters and survival status were
      then determined by immunohistochemistry in 116 ESCC and 50 normal specimens.
      Furthermore, bioinformatics was used for mechanisms exploration. And in vitro
      knockdown experiments were also performed. We found that COL11A1 expression was
      significantly higher in ESCC than in paired normal tissues at both mRNA and
      protein level. Immunohistochemistry showed that COL11A1 was predominantly
      localized to the cytoplasm rather than tumor stroma, patients with high COL11A1
      expression had a poorer overall survival (OS) rate than those with low COL11A1
      expression. Besides, increased COL11A1 expression was dramatically correlated
      with advanced clinical stage, invasion depth and lymph node metastases and served
      as an independent prognostic marker for ESCC. Likewise, COL11A1 dependent
      nomogram predicted a more precise survival outcome than traditional staging
      system. Moreover, COL11A1 silencing resulted in impaired cell proliferation and
      EMT, and subdued EMT inhibited cells aggressiveness. These biological processes
      (BPs) might be modulated by COL11A1 via the intracellular AKT/ERK/c-Myc cascades.

PMID- 29333919
TI  - Reconstruction of extensive medial canthal defects using a single V-Y, island
      pedicle flap.
AB  - The medial canthus represents one of the most challenging regions of the face to
      reconstruct due to the anatomical structures present, the concavity of the area,
      and the differences in skin texture. We present a case series of 11 patients
      whose defects were reconstructed with a single V-Y island pedicle flap running
      along the nasofacial sulcus. Our single-stage flap which modified and simplified
      a previously described technique achieves similar cosmetic and postoperative
      outcomes along with a high level of patient satisfaction in an area which can be
      reconstructed in a variety of ways, often with suboptimal results.

PMID- 29333920
TI  - Towards a psychology of sexual health.

PMID- 29333921
TI  - Targeting BRD4 proteins suppresses the growth of NSCLC through downregulation of
      eIF4E expression.
AB  - Lung cancer is the leading cause of cancer-related death worldwide. Bromodomain
      and extraterminal domain (BET) proteins act as epigenome readers for gene
      transcriptional regulation. Among BET family members, BRD4 was well studied, but
      for its mechanism in non-small cell lung carcinoma has not been elucidated. eIF4E
      regulates gene translation and has been proved to play an important role in the
      progression of lung cancer. In this study, we first confirmed that BET inhibitors
      JQ1 and I-BET151 suppressed the growth of NSCLCs, in parallel with downregulated
      eIF4E expression. Then we found that knockdown of BRD4 expression using siRNAs
      inhibited the growth of NSCLCs as well as decreased eIF4E protein levels.
      Moreover, overexpression of eIF4E partially abrogated the growth inhibitory
      effect of JQ1, while knockdown of eIF4E enhanced the inhibitory effect of JQ1.
      Furthermore, JQ1 treatment or knockdown of BRD4 expression decreased eIF4E mRNA
      levels and inhibited its promoter activity by luciferase reporter assay. JQ1
      treatment significantly decreased the binding of eIF4E promoter with BRD4.
      Finally, JQ1 inhibited the growth of H460 tumors in parallel with downregulated
      eIF4E mRNA and protein levels in a xenograft mouse model. These findings suggest
      that inhibition of BET by JQ1, I-BET151, or BRD4 silencing suppresses the growth
      of non-small cell lung carcinoma through decreasing eIF4E transcription and
      subsequent mRNA and protein expression. Considering that BET regulates gene
      transcription epigenetically, our findings not only reveal a new mechanism of BET
      regulated eIF4E in lung cancer, but also indicate a novel strategy by co
      targeting eIF4E for enhancing BET-targeted cancer therapy.

PMID- 29333923
TI  - Perception and Practice of HIV/AIDS Counseling and Testing Among Secondary School
      Adolescents in Ogun Waterside Local Government Area, Ogun State, Southwest
      Nigeria.
AB  - A large proportion of Nigerian adolescents are sexually active and the country
      has one of the highest HIV prevalence among youths globally. This study was done
      to assess the perception and practice of HIV/AIDS counseling and testing (HCT)
      among secondary school adolescents in a rural community in Southwest Nigeria. A
      cross-sectional descriptive study was carried out using multistage sampling
      method. The results showed that despite high level of HCT awareness, majority of
      the adolescents (62.9%) had negative attitude toward it. The practice of HCT was
      poor among majority of the respondents as less than 15% of the adolescents had
      ever done HCT. This study recommends that adolescents should be better informed
      on the locations of the health centers within the community and services rendered
      by them. Peer education on HCT should also be intensified in schools to promote
      positive healthy sexual lifestyles among adolescents.

PMID- 29333922
TI  - Effect of resveratrol treatment on graft revascularization after islet
      transplantation in streptozotocin-induced diabetic mice.
AB  - We evaluated the effect of resveratrol (RSV) on graft survival after islet
      transplantation (ITx) in diabetic mice. Isolated islets from Balb/c mice (200
      IEQ) were transplanted under the kidney capsule of diabetic Balb/c mice. Vehicle
      or RSV (200 mg/kg/day, orally) was given for 14 days after ITx. Two more control
      groups [STZ-treated (No-ITx-Control) and STZ+RSV-treated (No-ITx-RSV) mice
      without ITx] were added. Glucose tolerance tests (GTT) was performed at 14 days
      after ITx. In vitro, isolated islets pretreated with vehicle or RSV (1 MUM) were
      incubated in a hypoxic chamber (O2 1%, 1hr). Some of the ITx was performed in
      mouse insulin 1 gene promoter-green fluorescent protein (MIP-GFP) transgenic mice
      and analyzed using an in vivo imaging system. After 14 days of ITx, 2-hr glucose
      levels on GTT in the RSV-treated group were significantly lower than those of
      other control groups. But the glucose status was not improved in No-ITx mice with
      RSV. At day 3, the percentage of Ki-67/insulin co-stained cells in islet graft
      was significantly increased in the RSV-ITx group. Immunostaining with anti
      insulin and anti-BS-1 antibodies revealed significantly higher insulin-stained
      area and vascular density in RSV-treated islet grafts. The mean vessel volume per
      islet graft measured by in vivo imaging was significantly higher in the RSV
      treated group at day 3. In isolated islets cultured in hypoxic conditions, the
      cell death rate and oxidative stress were significantly attenuated with RSV
      pretreatment. Hypoxic treatment for isolated islets decreased the expression of
      SIRT-1 mRNA, and this attenuation was recovered by RSV pretreatment. Our data
      suggest that RSV treatment improved glycemic control, beta-cell proliferation,
      reduced oxidative stress, and enhanced islet revascularization and the outcome of
      ITx in diabetic mice.

PMID- 29333924
TI  - Dynamic MR imaging for functional vascularization depends on tissue factor
      signaling in glioblastoma.
AB  - Glomeruloid vascular proliferation (GVP) is a diagnostic hallmark and links to
      aggressive behavior, therapy resistance and poor prognosis in glioblastoma (GBM).
      It lacks clinical approaches to predict and monitor its formation and dynamic
      change. Yet the mechanism of GVPs also remains largely unknown. Using an in situ
      GBM xenograft mouse model, combined clinical MRI images of pre-surgery tumor and
      pathological investigation, we demonstrated that the inhibition of tissue factor
      (TF) decreased GVPs in Mouse GBM xenograft model. TF shRNA reduced microvascular
      area and diameter, other than bevacizumab. TF dominantly functions via PAR2/HB
      EGF-dependent activation under hypoxia in endothelial cells (ECs), resulting in a
      reduction of GVPs and cancer cells invasion. TF expression strongly correlated to
      GVPs and microvascular area (MVA) in GBM specimens from 56 patients, which could
      be quantitatively evaluated in an advanced MRI images system in 33 GBM patients.
      This study presented an approach to assess GVPs that could be served as a MRI
      imaging biomarker in GBM and uncovered a molecular mechanism of GVPs.

PMID- 29333925
TI  - Androgen receptor-independent prostate cancer: an emerging clinical entity.
AB  - Androgen deprivation therapy remains the backbone of prostate cancer treatment
      given its pivotal role in the pathogenesis of prostate cancer. The growing
      knowledge of androgen receptor-independent (i.e. AR-null) prostate cancer cells,
      however, might advance the treatment paradigm of prostate cancer. Here, we
      examined the results of two recent studies, published in Cancer Cell by Bluemn
      and Shukla et al., and their impact in the future management of castration
      resistant prostate cancer.

PMID- 29333926
TI  - Engrailed 1 overexpression as a potential prognostic marker in quintuple-negative
      breast cancer.
AB  - Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype
      characterized by poor patient prognosis and for which no targeted therapies are
      currently available. TNBC can be further categorized as either basal-like (BLBC)
      or quintuple-negative breast cancer (QNBC). In the present study, we aimed to
      identify novel molecular therapeutic targets for TNBC by analyzing the mRNA
      expression of TNBC-related genes in publicly available microarray data sets. We
      found that Engrailed 1 (EN1) was significantly overexpressed in TNBC. Using
      breast cancer cell lines, we found that EN1 was more highly expressed in TNBC
      than in other breast cancer subtypes. EN1 expression was analyzed in 199 TNBC
      paraffin-embedded tissue samples by immunohistochemistry. EN1 protein expression
      was positively associated with reduced overall survival (OS) rate in patients
      with QNBC, but not those with BLBC. The importance of EN1 expression in QNBC cell
      viability and tumorigenicity was evaluated using the QNBC cell lines, HCC38 and
      HCC1395. Based on our data, EN1 may promote the proliferation, migration, and
      multinucleation of QNBC cells, likely via the transcriptional activation of
      HDAC8, UTP11L, and ZIC3. We also demonstrated that actinomycin D effectively
      inhibits EN1 activity in QNBC cells. The results of the present study suggest
      that EN1 activity is highly clinically relevant to the survival prognosis of
      patients with QNBC and EN1 is a promising potential therapeutic target for future
      QNBC treatment.

PMID- 29333927
TI  - Comprehensive characterization of hydrothermal liquefaction products obtained
      from woody biomass under various alkali catalyst concentrations.
AB  - Hydrothermal liquefaction (HTL) of lignocellulosic biomass has been widely
      investigated for the production of renewable and alternative bio-crude oil. In
      this study, catalytic hydrothermal processing of two biomasses (larch and
      Mongolian oak) was performed using different K2CO3 concentrations (0, 0.1, 0.5,
      1.0 wt% of solvent) to improve fuel yield and properties. HTL oil, hydrochar,
      water-soluble fraction (WSF) and gas were characterized, and carbon balance was
      investigated. As a result, the maximum yield of HTL oil, 27.7 wt% (Mongolian oak)
      and 25.7 wt% (larch), and the highest carbon conversion ratio was obtained with
      0.5 wt% of catalyst. The high catalyst concentration also resulted in an increase
      in higher heating values up to 31.9 MJ/kg. In addition, the amount of organic
      compounds in HTL oil also increased, specifically for lignin-derived compounds
      including catechol and hydroquinone which can be derived from secondary
      hydrolysis of lignin. On the other hand, formation of hydrochar was suppressed
      with the addition of alkali catalyst and the yield dramatically decreased from
      30.7-40.8 wt.% to 20.0-21.8 wt.%. Furthermore, it was revealed that WSF had low
      organic carbon content less than 3.4% and high potassium content mostly derived
      from alkali catalyst, indicating that it may be reusable with simple
      purification. This work suggests that the addition of the proper amount of alkali
      catalyst can improve the production efficiency and quality of bio-crude oil, and
      another potential of WSF to be recyclable in further work.

PMID- 29333929
TI  - Efficacy of an imaging device at identifying the presence of bacteria in wounds
      at a plastic surgery outpatients clinic.
AB  - OBJECTIVE: Current standard diagnostic practice of bacterial infections by visual
      inspection under white light is subjective, and microbiological sampling is
      suboptimal due to high false negative rates and the lengthy time needed for
      culture results to arrive. The MolecuLight i:X Imaging Device attempts to combat
      the issues faced in standard practice by providing a non-contact, real-time
      method of visualising bacteria within wounds. Our aim was to test this imaging
      device in a series of patients. METHOD: A single-centre prospective observational
      study was conducted in the Queen Elizabeth Hospital, Birmingham. During Plastic
      Surgery Outpatient dressings clinics, patients had their wounds photographed with
      the imaging device under white light and violet light illumination.
      Microbiological swabs were obtained of all the wounds. Any clinical signs and
      symptoms of infection were noted. White light and violet light photographs were
      compared with correlate visible clinical signs and symptoms with auto
      fluorescence images. Auto-fluorescence images were then compared with the
      microbiological swab results to discern any differences. RESULTS: There were 14
      patients with seventeen separate wounds imaged. Of the 17, eight wounds were
      positive for bacterial growth on microbiological culture. All eight of these were
      detected positive for bacteria according to auto-fluorescence imaging. There was
      one wound was detected positive for bacteria by auto-fluorescence imaging with
      negative microbiological results. CONCLUSION: This study demonstrated the
      potential benefit of the imaging device due to the correlation between
      microbiological test results and auto-fluorescence imaging. The device greatly
      reduces the time taken waiting for results and it is simple, quick to use and non
      contact. There is potential for the imaging device to guide swab sampling and aid
      health professionals in the diagnosis and management of wound infections.

PMID- 29333930
TI  - A histological analysis of artificial skin in an extensively burned child, 14
      years after application: a case report.
AB  - INTRODUCTION: Artificial skin has become the treatment of choice in extensive,
      full-thickness thermal injuries. The longest follow-up of the healing process in
      burn sites covered with the Integra Bilayer Matrix Wound Dressing onto the wound
      published to date was at around five years after application. In our case report,
      we describe the clinical and histological analysis of an extensive, full
      thickness thermal injury 14 years on from treatment with the bilayer matrix wound
      dressing. CASE STUDY: A nine-year-old boy suffered a full-thickness skin loss
      over 85% of his body surface area following a fire accident. The bilayer matrix
      wound dressing was used on both legs and covered almost 30% of his body surface
      area. Cosmetic and functional results were satisfactory. Histological analysis
      performed nine years after the application of the bilayer matrix wound dressing
      onto the wound showed a double-layered skin composition with changes in the
      fibrous component of the dermis. CONCLUSION: Despite satisfactory short- and long
      term clinical results from applications of the bilayer matrix wound dressing, we
      found important differences in microstructure when compared with the
      physiological condition.

PMID- 29333928
TI  - Phosphorylation of STAT3 Promotes Vasculogenic Mimicry by Inducing Epithelial-to
      Mesenchymal Transition in Colorectal Cancer.
AB  - Vasculogenic mimicry refers to the process by which highly invasive cancer cells
      mimic endothelial cells by forming blood channels. Vasculogenic mimicry is
      important for the invasion and metastasis of tumor cells in colorectal cancer.
      STAT3 was initially identified as a mediator of the inflammation-associated acute
      phase response. The phosphorylation of Signal Transducers and Activators of
      Transcription 3 (p-STAT3) is closely related to tumor invasion and migration. We
      analyzed the relationship between p-STAT3 and vasculogenic mimicry formation in
      65 human colorectal cancer samples, and the results showed that the expression of
      p-STAT3 is significantly correlated with vasculogenic mimicry, tumor metastasis,
      Tumor, Lymph Node and Metastasis Stage (TNM Stage), and poor prognosis. It is
      known that interleukin 6 can induce the phosphorylation of STAT3. We found that
      using interleukin 6 to induce p-STAT3 activation in colorectal cancer cell lines
      can result in vasculogenic mimicry and using AG490 to suppress p-STAT3 activation
      restrained vasculogenic mimicry. Furthermore, the state of p-STAT3 activation can
      affect epithelial-to-mesenchymal transition. By immunofluorescence double
      staining, we discovered that p-STAT3 expression is more directly correlated with
      the epithelial-to-mesenchymal transition marker vimentin than with the
      vasculogenic mimicry-related protein VE-cadherin. These data show that activated
      p-STAT3 upregulates epithelial-to-mesenchymal transition-related proteins and
      promotes vasculogenic mimicry.

PMID- 29333931
TI  - Hyperspectral imaging of tissue perfusion and oxygenation in wounds: assessing
      the impact of a micro capillary dressing.
AB  - OBJECTIVE: Experimental tests of non-invasive multi- or hyperspectral imaging
      (HSI) systems reveal the high potential of support for medical diagnostic
      purposes and scientific biomedical analysis. Until now the use of HSI
      technologies for medical applications was limited by complex and overly
      sophisticated systems. We present a new and compact HSI-camera that could be used
      in normal clinical practice. METHOD: We assessed the use of the HSI system on the
      hands of 10 healthy volunteers, looking at control parameters, and those
      following venous occlusion, arterial occlusion and reperfusion, including tissue
      oxygenation, tissue haemoglobin index, perfusion in 4-6mm depth=near infrared
      spectroscopy (NIR), and tissue water index. Pseudo colours used ranged from 0%
      (blue) to 100% (red). We also assessed differences in the wounds of three
      patients. RESULTS: The results show good potential in all parameters in the
      healthy volunteers, which had high conformity with validated reference oximetry
      measurements. In three wounds, different levels of oxygenation were identified in
      the wound area, although interpretation of these results is complex. In Cases 2
      and 3, following the application of a micro capillary dressing, improvements were
      seen in perfusion and reduction of the tissue water index (TWI). CONCLUSION: The
      camera system proved to be quick, flexible and yielded data with high spatial and
      spectral resolution. These data will be used to perform a power analysis for a
      randomised controlled study.

PMID- 29333932
TI  - A comparison between DACC with chlorhexidine acetate-soaked paraffin gauze and
      foam dressing for skin graft donor sites.
AB  - OBJECTIVE: Retrograde infections often occur with excessive or incomplete
      drainage of exudate, or as a result of adherence of dressings to wounds.
      Dialkylcarbamoyl chloride (DACC) irreversibly binds to bacterial surfaces and
      physically removes bacteria when dressings are changed. Chlorhexidine acetate
      soaked paraffin gauze provides a moist wound-healing environment. We hypothesise
      that when DACC is combined with chlorhexidine acetate-soaked paraffin gauze,
      wound healing times decrease. METHOD: From January 2013 to June 2015, medical
      records were retrospectively evaluated in 60 patients who underwent split
      thickness skin grafts (STSG). Patients were divided into two groups: a 'thick
      skin group' and a 'thin skin group'. These two groups were further subdivided
      into a control group, where conventional foam dressings were applied to wounds,
      and an experimental group, where chlorhexidine acetate-soaked paraffin gauze with
      DACC was applied (DACC group). We compared the wound healing time between these
      subgroups. Differences in infected wound healing times were also compared. The
      Mann-Whitney test was applied to compare wound healing times between groups.
      RESULTS: Epithelialisation duration was significantly shorter in the DACC group.
      The control group had longer wound healing times, regardless of wound size. In
      the thick skin group, the median healing duration was 12 days in the control
      subgroup, compared with 9.5 days in the DACC subgroup (p=0.049). In the thin skin
      subgroup, the median healing duration in the control group was 18 days, compared
      with 10 days in the DACC subgroup (p=0.013). CONCLUSION: Application of DACC and
      chlorhexidine acetate-soaked paraffin gauze to skin graft donor sites can shorten
      healing times and is effective in treating infected wounds.

PMID- 29333933
TI  - Inspiration: the forgotten element in improving skin health and wound healing?

PMID- 29333934
TI  - Split-thickness skin grafting: early outcomes of a clinical trial using different
      graft thickness.
AB  - OBJECTIVE: In clinical practice, split-thickness skin graft (STSG)
      transplantation remains the gold standard for covering large skin defects.
      Currently, there is no consensus on the optimal thickness of skin grafts. The
      purpose of our study was to compare the early healing processes of recipient and
      donor wounds after STSG transplantation using grafts of different thickness.
      METHOD: This prospective, randomised clinical trial included 84 patients that
      underwent STSG transplantation surgery for post-burn, post-traumatic or
      postoperative skin defects. Patients were randomised to receive a skin graft of
      either 0.2mm, 0.3mm or 0.4mm thickness. After skin transplantation, the wound
      healing parameters of both the recipient and donor wounds were evaluated after
      three days, one week, two weeks and one month. RESULTS: The greatest mean
      epithelialisation scores and highest rate of complete wound epithelialisation
      were identified in the recipient and donor wounds of the 0.2mm transplant group,
      at all time points. When the recipient wound pain scores were evaluated, the
      greatest visual analogue scale (VAS) values were found in the 0.2mm transplant
      group. The opposite result was found for the donor wound, where the highest VAS
      scores were identified in the 0.4mm transplant group. There were no significant
      differences, at any follow-up period, when wound secretion, erythema, swelling,
      localised warmth and fluctuation were compared. CONCLUSION: The early healing of
      recipient wounds after STSG transplantation with grafts of various thickness
      differed considerably, especially regarding wound epithelialisation and pain.

PMID- 29333936
TI  - Disseminated histoplasmosis: a rare case presentation.

PMID- 29333935
TI  - Association between Human Papilloma Virus (HPV) vaccination and risk of Multiple
      Sclerosis: A systematic review.
AB  - INTRODUCTION: The vaccination against Humanpapilloma Virus (HPV) is an effective
      strategy to prevent high-risk HPV infection and subsequent cervical
      carcinogenesis. Although the safety profile has been ascertained, the relation
      with the development of central nervous system (CNS) autoimmune disorders (AD)
      appears still controversial. Multiple Sclerosis (MS) is the most common cause of
      chronic neurological impairment in young people, typically striking females. The
      main purpose of this review was to assess the association between HPV vaccination
      and MS. METHODS: The systematic review of the literature was carried out using 5
      search engines: MEDLINE, SCOPUS, ISI WEB OF KNOWLEDGE, GOOGLE SCHOLAR and
      ClinicalTrial.gov. The web search was updated on January 2017. PRISMA checklist
      was adopted to address the content of the systematic review. The measures of
      outcome were reported as relative risk (RR) in cohort studies and odds ratio (OR)
      in case-control studies. RESULTS: The systematic review identified 5
      observational studies, 9 reviews, and 1 randomized clinical trials (RCT) pooled
      analysis. The RR of MS onset detected by cohort studies ranged from 1.54 (95%CI,
      0.04-8.59) to 1.37 (95%CI, 0.74-3.20). Concerning case-control studies, the OR
      spanned from 0.3, (95%CI 0.1-0.9) to 1.60 (95%CI = 0.79-3.25) for the group
      exposed to HPV vaccination. No result was significant. CONCLUSION: This review
      showed no significant association between HPV vaccination and MS. The low
      statistical power of the studies agreed with the low incidence of MS disease
      among general population. In order to overcome the shortcoming the research may
      be extended to the entire pattern of CNS ADs.

PMID- 29333937
TI  - The Prevalence of Sexual Revictimization: A Meta-Analytic Review.
AB  - The literature consistently demonstrates evidence that child sexual abuse
      survivors are at greater risk of victimization later in life than the general
      population. This phenomenon is called sexual revictimization. Although this
      finding is robust, there is a large amount of variability in the prevalence rates
      of revictimization demonstrated in the literature. The purpose of the present
      meta-analysis was to calculate an average prevalence rate of revictimization
      across the literature and to examine moderators that may potentially account for
      the observed variability. Based on a review of PsycINFO and PILOTS, 1,412
      articles were identified and reviewed for inclusion. This process resulted in the
      inclusion of 80 studies, which contained 12,252 survivors of child sexual abuse.
      The mean prevalence of sexual revictimization across studies was 47.9% (95%
      confidence intervals [43.6%, 52.3%]), suggesting that almost half of child sexual
      abuse survivors are sexually victimized in the future. The present study failed
      to find support for any of the examined moderators. Potential explanations of and
      implications for the results are offered, including suggestions for therapists.

PMID- 29333938
TI  - Structure-based engineering to restore high affinity binding of an isoform
      selective anti-TGFbeta1 antibody.
AB  - Metelimumab (CAT192) is a human IgG4 monoclonal antibody developed as a TGFbeta1
      specific antagonist. It was tested in clinical trials for the treatment of
      scleroderma but later terminated due to lack of efficacy. Subsequent
      characterization of CAT192 indicated that its TGFbeta1 binding affinity was
      reduced by ~50-fold upon conversion from the parental single-chain variable
      fragment (scFv) to IgG4. We hypothesized this result was due to decreased
      conformational flexibility of the IgG that could be altered via engineering.
      Therefore, we designed insertion mutants in the elbow region and screened for
      binding and potency. Our results indicated that increasing the elbow region
      linker length in each chain successfully restored the isoform-specific and high
      affinity binding of CAT192 to TGFbeta1. The crystal structure of the high binding
      affinity mutant displays large conformational rearrangements of the variable
      domains compared to the wild-type antigen-binding fragment (Fab) and the low
      binding affinity mutants. Insertion of two glycines in both the heavy and light
      chain elbow regions provided sufficient flexibility for the variable domains to
      extend further apart than the wild-type Fab, and allow the CDR3s to make
      additional interactions not seen in the wild-type Fab structure. These
      interactions coupled with the dramatic conformational changes provide a possible
      explanation of how the scFv and elbow-engineered Fabs bind TGFbeta1 with high
      affinity. This study demonstrates the benefits of re-examining both structure and
      function when converting scFv to IgG molecules, and highlights the potential of
      structure-based engineering to produce fully functional antibodies.

PMID- 29333939
TI  - Parents' attitude, awareness and behaviour towards influenza vaccination in
      Pakistan.
AB  - National immunization program of Pakistan does not include Influenza vaccines.
      The low rate of immunization might be attributed to the poor knowledge of
      influenza vaccination in Pakistan. Current study was aimed to assess the
      knowledge and attitude of influenza vaccination among parents. A questionnaire
      based cross sectional study was conducted among randomly selected parents with at
      least one child aged >6 months. The responses were recorded against 27 items
      questionnaire assessing knowledge, perception, attitude and behaviours of
      parents. Data were analysed by using appropriate statistical methods. A total 532
      responses were recorded with male gender preponderance (65%). Most of the parents
      (61.1%) reported that their children had received or planned to receive all
      recommended vaccines in Expanded Program on Immunization (EPI) of Pakistan. Only
      one third of the parents (24.4%) were aware of the availability of influenza
      vaccines in Pakistan, and very few (6.6%) reported vaccinating their child
      against influenza. Exploring the parents' attitudes regarding children
      vaccination, the top motivator was 'immunization is important to keep my children
      healthy' (relative index = 0.93, p < 0.000). However, substantial number of
      parents believed that influenza is not a serious disease (18.5%) and vaccines are
      accompanied by several side effects (24.6%). A positive attitude was reflected
      among parents who were aware of influenza vaccines in Pakistan. About 35%
      participants believed that influenza vaccines are not required for healthy
      children. Current study demonstrated very low vaccination rate against influenza.
      Awareness and health literacy regarding influenza vaccine is poor among parents.
      These findings necessitate the need to appropriately structured awareness
      programs regarding influenza vaccination among parents.

PMID- 29333940
TI  - Expression analysis of liver-specific circulating microRNAs in HCV-induced
      hepatocellular Carcinoma in Egyptian patients.
AB  - OBJECTIVES: Due to the absence of reliable and accurate biomarkers for the early
      detection of liver malignancy, circulating microRNAs have recently emerged as
      great candidates for prompt cancer identification. Therefore, the aim of this
      study was to investigate the potential of liver-specific circulating microRNAs as
      an accurate non-invasive diagnostic tool for early diagnosis of hepatitis C virus
      (HCV)-induced hepatocellular carcinoma (HCC). METHODOLOGY: A total of 165
      patients were enrolled in this study and categorized into four main groups: 42
      chronic hepatitis C (CHC) without cirrhosis, 45 CHC with cirrhosis (LC), 38 HCC
      with HCV patients, and 40 healthy controls. The expression profiles of seven
      miRNAs (miR-16, miR-34a, miR-125a, miR-139, miR-145, miR-199a, and miR-221) were
      analyzed using real-time PCR. RESULTS: Serum levels of miRNA-125a, miRNA-139,
      miRNA-145, and miRNA199a were significantly lower (p < 0.01) in HCC than in both
      CHC and LC groups. On the other hand, no significant difference was shown in the
      expression of miR-16, miR-34a, and miR-221 between the CHC, LC, and HCC groups.
      MiR-16, miR-34a, and miR-221 were significantly elevated in the HCC group
      compared to the control group. MiR-34a showed the highest specificity and
      sensitivity. CONCLUSIONS: The results indicated that the measurement of serum
      levels of miR-125a, miR-139, miR-145, and miR-199a can help to differentiate HCC
      from CHC and LC. Also, miR-16, miR-34a, and miR-221 serum levels would have a
      prognostic value. MiR-34a had the highest specificity and sensitivity, indicating
      that it might serve as a novel and potential non-invasive biomarker for HCV
      induced HCC.

PMID- 29333941
TI  - Intraoperative Complications and Mid-Term Follow-Up of Large-Diameter Head Metal
      on-Metal Total Hip Arthroplasty and Hip Resurfacing Arthroplasty.
AB  - BACKGROUND AND AIMS: Large-diameter head total hip arthroplasty and hip
      resurfacing arthroplasty were popular in Finland from 2000 to 2012 for the
      treatment of hip osteoarthritis. The aim of this retrospective study was to
      investigate the mid-term survival of large-diameter head total hip arthroplasty
      patients operated on in three university hospitals and to compare these results
      to the survival of hip resurfacing arthroplasty patients. MATERIAL AND METHODS: A
      total of 3860 hip arthroplasties (3029 large-diameter head total hip
      arthroplasties in 2734 patients and 831 hip resurfacing arthroplasties in 757
      patients) were operated on between January 2004 and December 2009. The mean
      follow-up was 4.3 years (range: 0.3-8.0 years) in the total hip arthroplasty
      group and 5.1 years (range: 1.7-7.9 years) in the hip resurfacing arthroplasty
      group. Cox multiple regression model and Kaplan-Meier survival analysis were used
      to study the survival of the total hip arthroplasties and the hip resurfacing
      arthroplasties. Intraoperative complications and reasons for revisions were also
      evaluated. RESULTS: In Cox regression analysis, the hazard ratio for revision of
      hip resurfacing arthroplasty was 1.5 compared with large-diameter head total hip
      arthroplasty (95% confidence interval: 1.0-2.2) ( p = 0.029). The cumulative
      Kaplan-Meier survival rate was 90.7% at 7.7 years for the large-diameter head
      total hip arthroplasty (95% confidence interval: 86.8-94.6) and 92.2% at 7.6
      years for hip resurfacing arthroplasty (95% confidence interval: 89.9-94.6).
      There were a total of 166/3029 (5.5%) intraoperative complications in the large
      diameter head total hip arthroplasty group and 20/831 (2.4%) in the hip
      resurfacing arthroplasty group ( p = 0.001). Revision for any reason was
      performed on 137/3029 (4.5%) of the arthroplasties in the large-diameter head
      total hip arthroplasty group and 52/831 (6.3%) in the hip resurfacing
      arthroplasty group ( p = 0.04). CONCLUSION: The mid-term survival of both of
      these devices was poor, and revisions due to adverse reactions to metal debris
      will most likely rise at longer follow-up. There were more intraoperative
      complications in the large-diameter head total hip arthroplasty group than in the
      hip resurfacing arthroplasty group.

PMID- 29333942
TI  - SIX1 and DACH1 influence the proliferation and apoptosis of hepatocellular
      carcinoma through regulating p53.
AB  - ABSTRACTS This research aimed to explore effects of SIX1 and DACH1 on
      hepatocellular carcinoma (HCC) cell proliferation, apoptosis and cell cycle.
      Fifty paired hepatocellular carcinoma tissues were screened for differentially
      expressed genes. SIX1 and DACH1 expressions were subjected to qRT-PCR and western
      blot in tumor tissues and cells. The knockdown efficiency of siRNAs and
      transfection efficiency of cDNAs and siRNAs were validated by qRT-PCR and western
      blot as well. Then colony formation assay and flow cytometry were applied to
      observe cell proliferation, cell apoptosis and cell cycle changes.
      Immunofluorescence co-localization and immunoprecipitation were used to analyze
      the interaction between proteins which was quantified using western blot. Effects
      of SIX1 and DACH1 on tumor growth and their expressions in tumors were confirmed
      in vitro in nude mice model. Results of these experiments showed that SIX1 was
      overexpressed while DACH1 was suppressed in HCC tissues and cells. The
      suppression of SIX1 and overexpression of DACH1 not only inhibited cell
      proliferation, but also induced cell apoptosis and arrested cell cycle in G2/M
      phase compared with control group. Results of immunofluorescence co-localization
      suggested that SIX1, p53 and DACH1 were significantly overlapped.
      Immunoprecipitation showed that DACH1 (marked with Flag tag) could pull down p53
      and SIX1, but SIX1 (marked with His tag) could only pull down DACH1, which
      indicated that an indirect regulation between SIX1 and p53. Validated with
      western blot afterwards, DACH1 overexpression suppressed tumorigenesis in vivo by
      up-regulating p53 expression while SIX1 overexpression accelerated tumor growth
      by down-regulating p53 expression. Therefore, the decrease of SIX1 facilitated
      the expression of DACH1, thus activated the expression of p53 and suppressed the
      progression of HCC both in vitro and in vivo.

PMID- 29333943
TI  - Cyber-Victimization of People With Chronic Conditions and Disabilities: A
      Systematic Review of Scope and Impact.
AB  - The victimization of individuals with chronic conditions or disabilities is
      prevalent with severe impact at psychological and physiological levels. With the
      increasing use of technology these experiences were further reshaped. This
      systematic review aimed at scoping the experiences of cyber-victimization of
      people living with chronic conditions or disabilities and examine the documented
      impact on them. Following a four-stage search strategy in several databases
      including MEDLINE, Embase, PsychINFO, CINAHL, Cochrane and snowballing of
      references, a total of 2,922 studies were scanned and 10 studies were eventually
      included. Quality assessment was done in two phases using tools specific to
      observational studies and cyber-victimization research. A narrative synthesis of
      reported results covered a total of 3,070 people. Sample size ranged between 42
      and 823 participants, and the age range was 6-71 years with a majority of White
      ethnic backgrounds. Most studies (n=9) were cross sectional. The prevalence range
      of cyber-victimization was 2%-41.7% based on variable definitions, duration and
      methods. Targeted conditions included physical impairments, intellectual
      disabilities and specific chronic diseases. The most common documented impact was
      psychological/psychiatric, mainly depression followed by anxiety and distress.
      Somatic health complaints and self-harm were also reported. We concluded that
      people with chronic conditions and disabilities were consistently at higher risk
      of victimization with devastating health complications. Research gaps were
      identified such as the need to address more conditions and acknowledge
      differences between heterogeneous health conditions. Other recommendations
      include allowing flexibility and accountability to patients/victims in research
      design, education on victimization and health consequences, and improving primary
      care.

PMID- 29333944
TI  - MiR-155 Promotes Uveal Melanoma Cell Proliferation and Invasion by Regulating
      NDFIP1 Expression.
AB  - MicroRNAs refer to small RNA molecules that destroy the messenger RNA by binding
      on them inhibiting the production of protein. However, the role of miR-155 in
      uveal melanoma metastasis remains largely unknown. In this study, we found that
      miR-155 was upregulated in both uveal melanoma cells and tissues. Transfection of
      miR-155 mimic into uveal melanoma cells led to an increase in cell growth and
      invasion; in contrast, inhibition of miR-155 resulted in opposite effects. Also,
      we identified Nedd4-family interacting protein 1 as a direct target of miR-155,
      and the expression of Nedd4-family interacting protein 1 was inhibited by miR
      155. Furthermore, ectopic expression of Nedd4-family interacting protein 1
      restored the effects of miR-155 on cell proliferation and invasion of uveal
      melanoma cells. In conclusion, miR-155 acts as a tumor promotor in uveal melanoma
      through increasing cell proliferation and invasion. Thus, miR-155 might serve as
      a potential therapeutic target in patients with uveal melanoma.

PMID- 29333945
TI  - Remarkable response with pembrolizumab plus albumin-bound paclitaxel in 2 cases
      of HER2-positive metastatic breast cancer who have failed to multi-anti-HER2
      targeted therapy.
AB  - In clinical practice, one subgroup patients of breast cancer might have developed
      resistance to multi-anti-HER2 targeted drugs(trastuzumab, lapatinib and/or T-DM1)
      and can not benefit from the anti-HER2 targeted therapy continuously. We attempt
      to change the next therapic way for these patients. Two patients with metastatic
      breast cancer who have failed to multi-anti-HER2 targeted therapy were treated
      with pembrolizumab (2 mg/Kg, day1) plus albumin-bound paclitaxel (125 mg/m2,
      day1,8) every 3 weeks. CT evaluation and HER2 ECD test were performed every 2
      cycles. Both of the two patients achieved remarkable response with Partial
      Remission (PR), meanwhile serum HER2 ECD levels (the upper normal limit is 15
      ng/ml) showed a remarkable decreases(compared to the base line decreases 75% and
      60% respectively). The results indicate that regimen of pembrolizumab combination
      with albumin-bound paclitaxel might produce response in patients with HER2
      positive metastatic breast cancer who have failed to multi-anti-HER2 targeted
      therapy.

PMID- 29333946
TI  - Does inside passing contribute to the high incidence of groin injuries in soccer?
      A biomechanical analysis.
AB  - Groin injuries are common in soccer and often cause time-loss from training.
      While groin injuries have been linked to full effort kicking, the role of inside
      passing is unclear. Therefore, the purpose of this study was to investigate hip
      joint kinematics and muscle force, stress and contraction velocity for adductor
      longus and gracilis during inside passing. 3D kinematics of ten soccer players
      (23.4 yrs; 77.5 kg; 1.81 m) were captured with a motion capture system inside a
      Footbonaut. Muscle force and contraction velocity were determined with AnyBody
      Modelling System. Gracilis muscle forces were 9% lower compared to adductor
      longus (p = 0.005), but muscle stress was 183% higher in gracilis (p = 0.005).
      Contraction velocity reveals eccentric contraction of gracilis in the last
      quarter of the swing phase. Considering the combination of eccentric contraction,
      high muscle stress and the repetitive nature of inside passing, gracilis
      accumulates high loads in matches and training. These results indicate that the
      high incidence of groin injuries in soccer could be linked to isolated pass
      training. Practitioners need to be aware of the risk and refrain from sudden
      increases in the amount of pass training. This gives the musculoskeletal system
      time to adapt and might avoid career threatening injuries.

PMID- 29333948
TI  - Adult-Perpetrated Animal Abuse: A Systematic Literature Review.
AB  - Adults perpetrate the majority of animal abuse incidents yet clinicians are left
      with very little evidence base to advance/enhance their practice. The purpose of
      this systematic review is to synthesize and evaluate the current literature on
      adult-perpetrated animal abuse and to identify the etiological factors related to
      this type of offending. Twenty-three studies met the specific inclusion criteria
      but most importantly, they examined the characteristics of adult perpetrators of
      animal abuse. The findings from this review were demarcated by sample type: (1)
      Participants were the perpetrators of the animal abuse or held offense-supportive
      attitudes and (2) participants were victims of intimate partner violence
      reporting incidents of animal abuse perpetrated by their partner. From the
      perpetrator perspective, there were key developmental (i.e., maladaptive
      parenting strategies), behavioral (such as varied offending behaviors), and
      psychological (e.g., callousness, empathy deficits) factors highlighted in the
      literature. Finally, in the context of intimate partner violence, findings
      indicated that perpetrators abuse animals to control, coerce, intimidate, and/or
      manipulate their victims (this effect is moderated by the victims' emotional
      attachment to their pet). This review inherently underlines treatment targets
      that could achieve greater clinical gains, but we also conclude that more
      empirical and theoretical work is needed in order to set an agenda that
      prioritizes future research and effective practice.

PMID- 29333949
TI  - The "reading man" flap for reconstruction of large periorbital defects.
AB  - PURPOSE: The "reading man" flap (RMF), a double advancement transposition
      cutaneous flap named for its appearance, has been described in the reconstruction
      of various circular skin defects, particularly in the malar region. We describe
      two cases where this flap was used to reconstruct the lower eyelid/periorbital
      region. METHODS: Two oculoplastic patients with lower eyelid basal cell
      carcinomas underwent Mohs micrographic excision resulting in a large skin
      defects. In both cases, reconstruction was performed using the RMF. RESULTS: At 6
      months, both patients achieved good cosmetic results with no case of secondary
      eyelid malposition. CONCLUSION: The RMF is a useful adjunct to the armamentarium
      of the oculoplastic surgeon for the reconstruction of large periorbital defects.

PMID- 29333947
TI  - Persistence of hepatitis B immune memory until 9-10 years of age following
      hepatitis B vaccination at birth and DTaP-IPV-HB-PRP~T vaccination at 2, 4 and 6
      months.
AB  - OBJECTIVE: To evaluate the long-term persistence of anti-hepatitis B surface
      (HBs) antibodies and the response to a HB challenge re-vaccination in children
      who had received a primary series of DTaP-IPV-HB-PRP~T (HexaximTM) or DTaP-IPV
      HB/PRP~T (Infanrix hexaTM). METHODS: Two cohorts of participants who had
      previously received HB vaccine at birth followed by either DTaP-IPV-HB-PRP~T or
      DTaP-IPV-HB/PRP~T co-administered with PCV7 at 2, 4, 6 months of age in a
      randomized, Phase III, observer-blind study in Thailand, were followed up for
      anti-HBs antibodies (geometric mean concentrations [GMCs] and seroprotection [SP]
      rate [% of participants with a titer >=10 mIU/mL]) at 12-18 months of age and 9
      10 years of age. A monovalent HB challenge re-vaccination was administered at 9
      10 years of age and the anamnestic response was evaluated. RESULTS: Anti-HBs GMCs
      and SP rates in the DTaP-IPV-HB-PRP~T and DTaP-IPV-HB/PRP~T groups were high and
      similar post-primary vaccination series (2477 mIU/mL and 99.5% and 2442 mIU/mL
      and 99.5%, respectively) and declined to a similar extent in each group at 12-18
      months (154.5 mIU/mL and 90.8% and 162.3 mIU/mL and 96.5%, respectively).
      Antibody levels further declined at 9-10 years of age (13.3 mIU/mL and 49.3% and
      8.0 mIU/mL and 42.9%) and a strong anamnestic response occurred in each group
      post-HB challenge re-vaccination (92.8% and 98.7%, respectively). CONCLUSION: The
      kinetics of long-term anti-HBs antibody persistence were similar following a
      primary series of DTaP-IPV-HB-PRP~T or DTaP-IPV-HB/PRP~T. The response to a
      subsequent HB challenge re-vaccination was strong and similar in each group,
      demonstrating persisting immune memory.

PMID- 29333950
TI  - Willingness to pay for an Ebola vaccine during the 2014-2016 ebola outbreak in
      West Africa: Results from a U.S. National sample.
AB  - The 2014-2016 Ebola virus outbreak in West Africa led to advances in the
      development of vaccines against Ebola. This study examined factors associated
      with willingness to pay for an Ebola vaccine among a U.S. national sample during
      the recent Ebola outbreak. From April 30-May 8, 2015, a national survey was
      conducted using the GfK Group's KnowlegePanel(r). Main outcome measures included
      willingness to pay at least $1; more than $50; and more than $100 for an Ebola
      vaccine. Analyses were conducted using weighted multivariable logistic
      regression. Among participants (N = 1,447), 583 (40.3%) would not pay for an
      Ebola vaccine; 864 (59.7%) would pay at least $1. Among those willing to pay at
      least $1: 570 (66.0%) would pay $1-50; 174 (20.1%) would pay $51-100; and 120
      (13.9%) would pay more than $100. Willingness to pay at least $1 for an Ebola
      vaccine was associated with international travel; interest in getting an Ebola
      vaccine; and beliefs that the U.S. government should spend money to control Ebola
      and assume worldwide leadership in confronting emerging epidemics. Willingness to
      pay more than $50 was associated with similar variables. Willingness to pay more
      than $100 was associated with international travel; interest in getting an Ebola
      vaccine; information seeking; and beliefs that the U.S. government should assume
      worldwide leadership in confronting emerging epidemics. International travel and
      interest in an Ebola vaccine were key predictors of willingness to pay across all
      price points. Understanding willingness to pay for vaccines against emerging
      infectious diseases remains critical.

PMID- 29333951
TI  - A Systematic Review of Risk and Protective Factors for Externalizing Problems in
      Children Exposed to Intimate Partner Violence.
AB  - Intimate partner violence (IPV) is a serious public health issue with innumerable
      costs to the victims, children, and families affected as well as society at
      large. The evidence is conclusive regarding a strong association between exposure
      to IPV and children's externalizing problems. Moving forward, the next step is to
      enhance our understanding of risk and protective factors associated with these
      outcomes in order to tailor treatments to meet the needs of both parents and
      children. The databases Medline, PubMed, and PsyINFO were searched combining
      variations of the key words such as parent*, child*, mother, partner abuse,
      domestic abuse, spousal abuse, interpersonal violence, domestic violence, or
      intimate partner violence. This search were combined with child externalizing
      behaviors specifically conduct*, oppositional defiant disorder, externaliz*,
      aggress*, hyperactivity, and ADHD. A total of 31 studies from all three databases
      were reviewed following application of inclusion and exclusion criteria. The main
      findings were that child age and gender, callous-unemotional traits, cognitive
      appraisals, maternal mental health, and quality of parenting emerged as key
      mediating and moderating factors of the relationship between IPV exposure and
      child externalizing problems. These findings suggest that interventions provided
      to families exposed to IPV need to target both maternal and child risk factors in
      order to successfully reduce child externalizing problems.

PMID- 29333952
TI  - Trauma Intervention in Sub-Saharan African Children: A Systematic Literature
      Review.
AB  - Sub-Saharan Africa is a part of the world that is highly affected by a large
      number of atrocities, causing a myriad of financial, physical health, and mental
      health consequences. Yet, unfortunately, according to the World Health
      Organization (WHO), this is also the part of the world that is least served by
      mental health services. In response, the WHO has created mandates to increase
      mental health resources and capacity in all countries. Researchers have taken on
      the work of introducing and adapting treatments in various sub-Saharan African
      countries with an aim to create sustainable, evidence-based treatment in a part
      of the world with high need. The current qualitative systematic review of the
      literature examines 20 articles that report on research conducted in sub-Saharan
      African countries with children who have suffered different types of traumas.
      This review answers questions concerning the types of treatments used, the people
      administering the treatments, the measures they take to adapt these treatments,
      and the types of outcomes that are seen. Overall, the majority of treatments
      being used are shown to be effective with the associated populations.

PMID- 29333953
TI  - The irreversible ERBB1/2/4 inhibitor neratinib interacts with the BCL-2 inhibitor
      venetoclax to kill mammary cancer cells.
AB  - The irreversible ERBB1/2/4 inhibitor, neratinib, down-regulates the expression of
      ERBB1/2/4 as well as the levels of MCL-1 and BCL-XL. Venetoclax (ABT199) is a BCL
      2 inhibitor. At physiologic concentrations neratinib interacted in a synergistic
      fashion with venetoclax to kill HER2 + and TNBC mammary carcinoma cells. This was
      associated with the drug-combination: reducing the expression and phosphorylation
      of ERBB1/2/3; in an eIF2alpha-dependent fashion reducing the expression of MCL-1
      and BCL-XL and increasing the expression of Beclin1 and ATG5; and increasing the
      activity of the ATM-AMPKalpha-ULK1 S317 pathway which was causal in the formation
      of toxic autophagosomes. Although knock down of BAX or BAK reduced drug
      combination lethality, knock down of BAX and BAK did not prevent the drug
      combination from increasing autophagosome and autolysosome formation. Knock down
      of ATM, AMPKalpha, Beclin1 or over-expression of activated mTOR prevented the
      induction of autophagy and in parallel suppressed tumor cell killing. Knock down
      of ATM, AMPKalpha, Beclin1 or cathepsin B prevented the drug-induced activation
      of BAX and BAK whereas knock down of BID was only partially inhibitory. A 3-day
      transient exposure of established estrogen-independent HER2 + BT474 mammary
      tumors to neratinib or venetoclax did not significantly alter tumor growth
      whereas exposure to [neratinib + venetoclax] caused a significant 7-day
      suppression of growth by day 19. The drug combination neither altered animal body
      mass nor behavior. We conclude that venetoclax enhances neratinib lethality by
      facilitating toxic BH3 domain protein activation via autophagy which enhances the
      efficacy of neratinib to promote greater levels of cell killing.

PMID- 29333954
TI  - Prevalence, Diagnosis, and Treatment Rates of Mood Disorders among Opioid Users
      under Criminal Justice Supervision.
AB  - BACKGROUND: Individuals involved in the criminal justice system have
      disproportionately high rates of psychiatric disorders when compared to the
      general U.S. POPULATION: If left untreated, the likelihood of subsequent arrest
      increases and risk for adverse health consequences is great, particularly among
      opioid users. OBJECTIVES: To explore the prevalence, characteristics, and
      treatment of mood disorders among justice involved opioid-dependent populations.
      METHODS: The current study enrolled 258 treatment-seeking opioid-dependent
      individuals under community-based criminal justice supervision (e.g., probation,
      parole) screened from the larger parent study, Project STRIDE, a seek/test/treat
      randomized control trial (RCT) examining HIV and opioid use treatment. During
      baseline, individuals were screened for depression using the Patient Health
      Questionnaire-9 (PHQ-9) and screened for bipolar disorder using the Mood Disorder
      Questionnaire (MDQ) tool. RESULTS: Overall, 78 (30%) participants screened
      positive for moderate to severe depression and 54 (21%) screened positive for
      bipolar disorder. Participants self-reported mood disorders at higher rates than
      they screened positive for these conditions. Participants screening positive for
      these conditions experienced significantly greater family, legal, and medical
      problems on the Addiction Severity Index-Lite (ASI-Lite) than those who did not
      screen positive. Incidence of a lifetime suicide attempt was found to be
      associated with a positive screen for both mood disorders. Prescribed
      psychotropic treatment utilization was similar among those who screened positive
      for depression or bipolar disorder with approximately 38% reporting taking
      medication. IMPORTANCE: Findings suggest universal mood disorder screening to
      improve comprehensive psychiatric care and treatment of opioid-dependent justice
      involved individuals.

PMID- 29333955
TI  - The Relationship Between Internalized Homophobia and Intimate Partner Violence in
      Same-Sex Relationships: A Meta-Analysis.
AB  - A meta-analysis was conducted to investigate the association between internalized
      homophobia and intimate partner violence (IPV) perpetration and victimization in
      same-sex relationships. The literature search and the application of the
      inclusion criteria made it possible to identify 10 studies, 2 of which were
      excluded due to missing data. Therefore, eight studies were finally included in
      the meta-analysis. The results showed positive and statistically significant
      associations between internalized homophobia and IPV perpetration and
      victimization, indicating that higher levels of internalized homophobia were
      related to higher levels of IPV. Specifically, the pooled effect size for the
      relationship between internalized homophobia and IPV perpetration (all forms), it
      was r+ = .147, 95% confidence interval (CI) = [.079, .214]; for the association
      between internalized homophobia and physical/sexual IPV perpetration, it was r+ =
      .166, 95% CI [.109, .221]; p < .0001; for the relationship between internalized
      homophobia and psychological IPV perpetration, it was r+ = .145, 95% CI [.073,
      .216]; and for the association between internalized homophobia and any type of
      IPV victimization, it was r+ = .102, 95% CI [.030, .173]. Implications of these
      results for clinical practice and future research are discussed.

PMID- 29333956
TI  - High-efficiency treatment of PTA wastewater using a biogas jet assisted anaerobic
      fluidized bed reactor.
AB  - In this paper, a new type of biogas jet assisted anaerobic fluidized bed reactor
      loaded with a polypropylene carrier has been proposed. There was a clear
      improvement in the fluidized state due to the biogas assisted input when the
      gas/water ratio was set at 1:3 with a suitable carrier loading of 60%. When the
      circulating water flow is 30 L/min assisted with biogas 10 L/min, the mixing time
      shortens from 26 to 18 s. The performance of anaerobic biodegradation on
      wastewater treatment was improved largely. The chemical oxygen demand (COD) and
      terepthallic acid removal efficiencies were at 85.4% and 84%, respectively, at
      hydraulic retention time of 20 h, even when the influent COD concentration was as
      high as 4224 mg/L. In addition, plenty of microorganisms, attached to the
      carriers and assumed to be the reason behind the organic biodegradation
      efficiency of the proposed system, were observed using scanning electron
      microscopy.

PMID- 29333957
TI  - MiR-98 Promotes Apoptosis of Glioma Cells via Suppressing IKBKE/NF-kappaB
      Pathway.
AB  - The inhibitor of kappa B kinase epsilon is overexpressed in glioma and plays
      antiapoptotic role via activating nuclear factor-kappa B. microRNA-98 can
      suppress glioma, modulate the activities of nuclear factor-kappa B, and bind to
      the 3'-untranslated region of inhibitor of kappa B kinase epsilon messenger RNA.
      This study was aimed to investigate the modulation of inhibitor of kappa B kinase
      epsilon/nuclear factor-kappa B by microRNA-98 in glioma. The results indicated
      that microRNA-98 was downregulated in glioma cell lines and human glioma tissues.
      Overexpression of microRNA-98 in U87MG and T98G glioma cells significantly
      increased the apoptosis induced by ultraviolet irradiation and suppressed nuclear
      factor-kappa B luciferase activity, nuclear factor-kappa B p50 subunit
      expression, and B-cell lymphoma-2 (Bcl-2) expression in glioma cells. Silencing
      inhibitor of kappa B kinase epsilon decreased the expression of nuclear factor
      kappa B p50 subunit and the luciferase activity of nuclear factor-kappa B, while
      the nuclear factor-kappa B activity could be significantly retrieved when
      inhibitor of kappa B kinase epsilon was expressed in microRNA-98-transfected
      cells. These findings indicated that microRNA-98 could promote apoptosis of
      glioma cells via inhibiting inhibitor of kappa B kinase epsilon/nuclear factor
      kappa B signaling and presented a novel regulatory pathway of microRNA-98 by
      direct suppression of inhibitor of kappa B kinase epsilon/nuclear factor-kappa B
      expression in glioma cells.

PMID- 29333958
TI  - Focal MRI-Guided Salvage High-Dose-Rate Brachytherapy in Patients With
      Radiorecurrent Prostate Cancer.
AB  - INTRODUCTION: Whole-gland salvage treatment of radiorecurrent prostate cancer has
      a high rate of severe toxicity. The standard of care in case of a biochemical
      recurrence is androgen deprivation treatment, which is associated with morbidity
      and negative effects on quality of life. A salvage treatment with acceptable
      toxicity might postpone the start of androgen deprivation treatment, might have a
      positive influence on the patients' quality of life, and might even be curative.
      Here, toxicity and biochemical outcome are described after magnetic resonance
      imaging-guided focal salvage high-dose-rate brachytherapy in patients with
      radiorecurrent prostate cancer. MATERIALS AND METHODS: Seventeen patients with
      pathologically proven locally recurrent prostate cancer were treated with focal
      high-dose-rate brachytherapy in a single 19-Gy fraction using magnetic resonance
      imaging for treatment guidance. Primary radiotherapy consisted of external beam
      radiotherapy or low-dose-rate brachytherapy. Tumors were delineated with Ga-68
      prostate-specific membrane antigen or F18-choline positron emission tomography in
      combination with multiparametric magnetic resonance imaging. All patients had a
      prostate-specific antigen level of less than 10 ng/mL at the time of recurrence
      and a prostate-specific antigen doubling time of >=12 months. Toxicity was
      measured by using the Common Terminology Criteria for Adverse Events version 4.
      RESULTS: Eight of 17 patients had follow-up interval of at least 1 year. At a
      median follow-up interval of 10 months (range 3-40 months), 1 patient experienced
      a biochemical recurrence according to the Phoenix criteria, and prostate-specific
      membrane antigen testing revealed that this was due to a distant nodal
      metastasis. One patient had a grade 3 urethral stricture at 2 years after
      treatment. CONCLUSION: Focal salvage high-dose-rate brachytherapy in patients
      with radiorecurrent prostate cancer showed grade 3 toxicity in 1 of 17 patients
      and a distant nodal metastasis in another patient. Whether this treatment option
      leads to cure in a subset of patients or whether it can successfully postpone
      androgen deprivation treatment needs further investigation.

PMID- 29333960
TI  - A Meta-Analysis of Risk and Protective Factors for Dating Violence Victimization:
      The Role of Family and Peer Interpersonal Context.
AB  - Dating violence (DV) is a widespread social issue that has numerous deleterious
      repercussions on youths' health. Family and peer risk factors for DV have been
      widely studied, but with inconsistent methodologies, which complicates global
      comprehension of the phenomenon. Protective factors, although understudied,
      constitutes a promising line of research for prevention. To date, there is no
      comprehensive quantitative review attempting to summarize knowledge on both
      family and peer factors that increase or decrease the risk for adolescents and
      emerging adults DV victimization. The current meta-analysis draws on 87 studies
      with a total sample of 278,712 adolescents and young adults to examine effect
      sizes of the association between various family and peer correlates of DV
      victimization. Results suggest small, significant effect sizes for all the family
      (various forms of child maltreatment, parental support, and parental monitoring)
      and peer factors (peer victimization, sexual harassment, affiliation with deviant
      peers, and supportive/prosocial peers) in the prediction of DV. With few
      exceptions, forms of DV (psychological, physical, and sexual), gender, and age
      did not moderate the strength of these associations. In addition, no difference
      was found between the magnitude of family and peer factors' effect sizes,
      suggesting that these determinants are equally important in predicting DV. The
      current results provide future directions for examining relations between risk
      and protective factors for DV and indicate that both peers and family should be
      part of the development of efficient prevention options.

PMID- 29333959
TI  - A Noninvasive Body Setup Method for Radiotherapy by Using a Multimodal Image
      Fusion Technique.
AB  - PURPOSE: To minimize the mismatch error between patient surface and
      immobilization system for tumor location by a noninvasive patient setup method.
      MATERIALS AND METHODS: The method, based on a point set registration, proposes a
      shift for patient positioning by integrating information of the computed
      tomography scans and that of optical surface landmarks. An evaluation of the
      method included 3 areas: (1) a validation on a phantom by estimating 100 known
      mismatch errors between patient surface and immobilization system. (2) Five
      patients with pelvic tumors were considered. The tumor location errors of the
      method were measured using the difference between the proposal shift of cone-beam
      computed tomography and that of our method. (3) The collected setup data from the
      evaluation of patients were compared with the published performance data of other
      2 similar systems. RESULTS: The phantom verification results showed that the
      method was capable of estimating mismatch error between patient surface and
      immobilization system in a precision of <0.22 mm. For the pelvic tumor, the
      method had an average tumor location error of 1.303, 2.602, and 1.684 mm in left
      right, anterior-posterior, and superior-inferior directions, respectively. The
      performance comparison with other 2 similar systems suggested that the method had
      a better positioning accuracy for pelvic tumor location. CONCLUSION: By
      effectively decreasing an interfraction uncertainty source (mismatch error
      between patient surface and immobilization system) in radiotherapy, the method
      can improve patient positioning precision for pelvic tumor.

PMID- 29333961
TI  - Helping Survivors of Human Trafficking: A Systematic Review of Exit and Postexit
      Interventions.
AB  - BACKGROUND: Human trafficking is a global problem and results in deleterious
      psychological, social, and physical effects on the lives of those who are
      trafficked; however, it is not clear how to best intervene with survivors. The
      purpose of this review was to synthesize the evidence of exit and postexit
      intervention programs for survivors of human trafficking to inform practice and
      research. METHOD: Systematic review methods were used to search, select, and
      extract data from published and unpublished experimental, quasi-experimental, and
      preexperimental studies that assessed the effects of any exit or postexit
      interventions for victims of human trafficking. The authors searched eight
      databases, reviewed bibliographies, and conducted forward citation searches from
      relevant reports and prior reviews to find studies authored between 2005 and
      2015. RESULTS: The search yielded six eligible studies that included 155 female
      and 6 male survivors from four countries. Interventions were diverse, with three
      using a trauma-informed approach. Authors measured a myriad of outcomes,
      including mental health, social network, community reintegration, and employment;
      however, the quality of most studies was poor. DISCUSSION: Evidence of effects of
      exit and postexit interventions is sparse, and much of the research is poorly
      designed and executed; however, the needs of trafficking survivors are complex
      and effective interventions are desperately needed. Implications for practice and
      research are discussed.

PMID- 29333962
TI  - Childhood Maltreatment and the Risk for Criminal Justice Involvement and
      Victimization Among Homeless Individuals: A Systematic Review.
AB  - Homeless individuals are at higher risk of criminal justice involvement (CJI) and
      victimization compared to their housed counterparts. Exposure to childhood
      maltreatment (CM; e.g., abuse, neglect) is one of the most significant predictors
      of CJI and victimization among homeless populations. The aim of this systematic
      review was to synthesize current knowledge regarding the relationship between CM
      and CJI and victimization among homeless individuals. Guided by the preferred
      reporting items for systematic reviews and meta-analyses (PRISMA) methods, a
      systematic search was performed using PsycINFO, MEDLINE, Embase, Web of Science,
      and the Cumulative Index to Nursing and Allied Health Literature for published
      studies investigating the relationship between CM and CJI and victimization among
      homeless samples. We identified 20 studies that met the inclusion criteria.
      Findings showed that across the majority of studies, CM, and in particular
      childhood physical (CPA) and sexual (CSA) abuse, is associated with increased
      risk of both CJI and victimization, regardless of various important factors
      (e.g., sociodemographic characteristics, psychiatric disorders, substance use).
      These findings support the need for prevention and treatment for "families at
      risk" (i.e., for intimate partner violence, child abuse and neglect) and also
      document the need for trauma-informed approaches within services for homeless
      individuals. Future research should focus on prospective designs that examine
      victimization and CJI in the same samples.

PMID- 29333963
TI  - The Differential Victimization Associated With Depression and Anxiety in Cross
      Cultural Perspective: A Meta-Analysis.
AB  - Traditional bullying and cyberbullying have become serious worldwide issues. The
      meta-analysis in this article took a cross-cultural perspective to explore
      whether there were any differences between the effects of cyber victimization and
      traditional victimization on the presence of depression and anxiety in children
      and adolescents and to examine the effects of moderators in explaining these
      differences/similarities. Fifty-six empirical studies (generating 148 independent
      samples) were included with a total sample size of 214,819 participants. The
      results indicated that the effects of cyber victimization and the subtypes of
      traditional victimization on anxiety were significantly different, and there was
      a marginally significant difference for depression. The moderating effects of
      country of origin were found to be significant for depression, with the mean
      effect size in North America being significantly higher than in China and Europe,
      which suggested that culture was an important factor. The moderating effects of
      age were also found to be significant for the relationships between traditional
      victimization and depression, traditional victimization and anxiety, cyber
      victimization and depression, and cyber victimization and anxiety. In addition,
      the effect size for cyber victimization and depression has increased in more
      recent publication years.

PMID- 29333964
TI  - The Scale of Sexual Aggression in Southeast Asia: A Review.
AB  - Southeast Asia is one of the most dynamic regions in the world. It is
      experiencing rapid socioeconomic change that may influence the level of sexual
      aggression, but data on the scale of sexual aggression in the region remain
      sparse. The aim of the present article was to systematically review the findings
      of studies available in English on the prevalence of self-reported sexual
      aggression and victimization among women and men above the age of 12 years in the
      11 countries of Southeast Asia (Brunei, Cambodia, East Timor, Indonesia, Laos,
      Malaysia, Myanmar, the Philippines, Singapore, Thailand, and Vietnam). Based on
      four scientific databases, the search engine Google, Opengrey database, and
      reference checking, 49 studies were found on sexual victimization. Of those, 32
      included only women. Self-reported perpetration was assessed by only three
      studies and included all-male samples. Prevalence rates varied widely across
      studies but showed that sexual victimization was widespread among different
      social groups, irrespective of sex and sexual orientation. Methodological
      heterogeneity, lack of representativeness of samples, imbalance of information
      available by country, missing information within studies, and cultural
      differences hampered the comparability between and within countries. There is a
      need for operationalizations that specifically address sexual aggression
      occurring after the age of consent, based on detailed behavioral descriptions of
      unwanted sexual experiences and allied to a qualitative approach with cultural
      sensitivity. Data on sexual aggression in conflict settings and in human
      trafficking are also limited. Recommendations for future research are presented
      in the discussion.

PMID- 29333965
TI  - Prevalence of Sexual Aggression Victimization and Perpetration in Chile: A
      Systematic Review.
AB  - Sexual aggression is a major public health issue worldwide, but most knowledge is
      derived from studies conducted in North America and Western Europe. Little
      research has been conducted on the prevalence of sexual aggression in developing
      countries, including Chile. This article presents the first systematic review of
      the evidence on the prevalence of sexual aggression victimization and
      perpetration among women and men in Chile. Furthermore, it reports differences in
      prevalence rates in relation to victim and perpetrator characteristics and victim
      perpetrator relationships. A total of N = 28 studies were identified by a three
      stage literature search, including the screening of academic databases,
      publications of Chilean institutions, and reference lists. A great heterogeneity
      was found for prevalence rates of sexual victimization, ranging between 1.0% and
      51.9% for women and 0.4% and 48.0% for men. Only four studies provided
      perpetration rates, which varied between 0.8% and 26.8% for men and 0.0% and
      16.5% for women. No consistent evidence emerged for differences in victimization
      rates in relation to victims' gender, age, and education. Perpetrators were more
      likely to be persons known to the victim. Conceptual and methodological
      differences between the studies are discussed as reasons for the great
      variability in prevalence rates, and recommendations are provided for a more
      harmonized and gender-inclusive approach for future research on sexual aggression
      in Chile.

PMID- 29333966
TI  - The Impacts of Sexual Media Exposure on Adolescent and Emerging Adults' Dating
      and Sexual Violence Attitudes and Behaviors: A Critical Review of the Literature.
AB  - Dating violence (DV) and sexual violence (SV) are widespread problems among
      adolescents and emerging adults. A growing body of literature demonstrates that
      exposure to sexually explicit media (SEM) and sexually violent media (SVM) may be
      risk factors for DV and SV. The purpose of this article is to provide a
      systematic and comprehensive literature review on the impact of exposure to SEM
      and SVM on DV and SV attitudes and behaviors. A total of 43 studies utilizing
      adolescent and emerging adult samples were reviewed, and collectively the
      findings suggest that (1) exposure to SEM and SVM is positively related to DV and
      SV myths and more accepting attitudes toward DV and SV; (2) exposure to SEM and
      SVM is positively related to actual and anticipated DV and SV victimization,
      perpetration, and bystander nonintervention; (3) SEM and SVM more strongly impact
      men's DV and SV attitudes and behaviors than women's DV and SV attitudes and
      behaviors; and (4) preexisting attitudes related to DV and SV and media
      preferences moderate the relationship between SEM and SVM exposure and DV and SV
      attitudes and behaviors. Future studies should strive to employ longitudinal and
      experimental designs, more closely examine the mediators and moderators of SEM
      and SVM exposure on DV and SV outcomes, focus on the impacts of SEM and SVM that
      extend beyond men's use of violence against women, and examine the extent to
      which media literacy programs could be used independently or in conjunction with
      existing DV and SV prevention programs to enhance effectiveness of these
      programming efforts.

PMID- 29333967
TI  - A Meta-Analysis of Risk Markers for Intimate Partner Violence in Same-Sex
      Relationships.
AB  - Research on intimate partner violence (IPV) has largely focused on heterosexual
      relationships, but, in recent years, researchers have expanded their focus to
      include same-sex relationships. Using meta-analytic techniques, this study was
      conducted to examine the relative strength of various risk markers for men and
      women being perpetrators and victims of physical IPV in same-sex relationships.
      Articles were identified through research search engines and screened to identify
      articles fitting the inclusion criteria, a process that resulted in 24 studies
      and 114 effect sizes for the meta-analysis. The strongest risk marker among those
      with at least two effect sizes for both male and female perpetration was
      psychological abuse perpetration. The strongest risk marker among those with at
      least two effect sizes for IPV victimization was also perpetration of
      psychological abuse for males and psychological abuse victimization for females.
      Among same-sex-specific risk markers, internalized homophobia and fusion were the
      strongest predictors for being perpetrators of IPV for men and women,
      respectively. HIV status and internalized homophobia were the strongest risk
      markers for IPV victimization for men and women, respectively. Of 10 comparisons
      between men and women in risk markers for IPV perpetration and victimization,
      only 1 significant difference was found. The results suggest that although same
      sex and heterosexual relationships may share a number of risk markers for IPV,
      there are risk markers for physical IPV unique to same-sex relationships. Further
      research and increased specificity in measurement are needed to better study and
      understand the influence of same-sex-specific risk markers for IPV.

PMID- 29333968
TI  - The Complexity of Adaptation to Childhood Polyvictimization in Youth and Young
      Adults: Recommendations for Multidisciplinary Responders.
AB  - Exposure to violence is pervasive in our society. An abundance of research has
      demonstrated that individuals who experience polyvictimization (PV)-prolonged or
      multiple forms of traumatic victimizations-are at heightened risk for continuing
      to experience repeated victimizations throughout their lifetimes. The current
      article reviews several overlapping constructs of traumatic victimizations with
      the ultimate goal of providing a unifying framework for conceptualizing prolonged
      and multiple victimization (defined in this article as PV) as a precursor to
      complex post-traumatic biopsychosocial adaptations, revictimization, and in some
      instances reenactment as a perpetrator (defined as complex trauma [CT]). This
      model is then applied to three socially disadvantaged victim populations-lesbian,
      gay, bisexual, transgender, queer, or questioning; commercially sexually
      exploited individuals; and urban communities of color-who are at heightened risk
      for PV and for exhibiting complex clinical presentations to demonstrate how the
      PV-CT framework can destigmatize, reframe, and ultimately reduce health
      disparities experienced by these populations. Trauma-informed recommendations are
      provided to aid researchers and multidisciplinary providers working to reduce
      harm and improve the quality of life for polyvictims.

PMID- 29333969
TI  - Sexual Violence Against Older People: A Review of the Empirical Literature.
AB  - Aging and sexual violence are both established areas of research, but little
      attention has been paid to research into sexual violence against older people.
      This article presents a critical review of the literature reporting empirical
      research in three overlapping fields of inquiry: elder abuse, domestic violence,
      and sexual violence, identifying points of theoretical and methodological
      similarity and difference across academic disciplines. Using a range of search
      terms combining age, sexual violence, and elder abuse, the following databases
      were searched: EBSCOHOST, Ingenta-Ingenta connect, and JSTOR. In total, the
      databases searches returned 31 relevant articles and an additional 9 relevant
      articles were found through manual searches of bibliographies and Google
      searches, which were grouped into three categories: elder abuse, domestic
      violence in later life, and sexual violence against older people. Four themes
      common across these fields emerged: prevalence, characteristics of victims and
      risk factors, impacts and coping strategies, and perpetrator and assault
      characteristics. The findings in each area are discussed in detail, exposing gaps
      in knowledge and understandings of sexual violence against older women. The
      article ends by defining a future research agenda for this underexplored
      phenomenon that is of increasing importance in a context of global aging.

PMID- 29333970
TI  - Parental Migration, Children's Safety and Psychological Adjustment in Rural
      China: A Meta-Analysis.
AB  - Studies concerning left-behind children in rural China have shown that parental
      absence due to migration is associated with greater risk of child victimization
      and accidental injuries, and a range of psychosocial problems. The authors
      conducted this meta-analysis to determine the extent to which left-behind
      children are affected by parental migration, as compared to children in
      nonmigrant rural families. A comprehensive literature search was conducted, and
      90 studies published before 2017 were included in the data synthesis and
      analysis. The results revealed that compared to non-left-behind children, rural
      left-behind children are generally more disadvantaged in regard to child safety (
      d = 0.27) and psychological adjustment ( d = 0.25). The effect sizes, though
      interpreted as small, revealed that children in rural China are significantly
      affected by parental migration. Children's educational stage was a significant
      variable that moderated the effect sizes of child safety and psychological
      adjustment. The findings of the meta-analysis indicated that mother-only
      migration may have the most harmful effect on children. In terms of implications
      for interventions, the results suggest more attention should be given to rural
      left-behind children and to "mother-absent children" in particular. Future
      research is warranted to explore the association between left-behind children's
      psychological adjustment and their exposure to injury and victimization.

PMID- 29333971
TI  - Using Photovoice to Address Gender-Based Violence: A Qualitative Systematic
      Review.
AB  - The purpose of this article is to examine how photovoice research addresses
      gender-based violence (GBV) among individuals and communities that experience and
      witness GBV. Photovoice action research (PVAR) methods act as both an
      intervention and a research method by engaging participants in using photography
      to depict a topic of concern and in developing potential solutions. To date,
      there is not a published review of PVAR publications that focus on addressing
      GBV. This article is comprised of a qualitative systematic review of studies that
      use photovoice research methods to address GBV. This review is conducted in
      accordance with the Supplementary Guidance of the Cochrane handbook and results
      in the examination of 17 publications that meet inclusion criteria. The data
      synthesis engages grounded theory (GT) methods and results in the emergence of
      one primary category transgressing the violence and three subcategories
      illustrating the problem, caring for self and others, and harnessing community
      resources. The results of this review reveal research, practice, and policy
      implications for photovoice projects aimed at addressing GBV.

PMID- 29333972
TI  - Interventions in Health Settings for Male Perpetrators or Victims of Intimate
      Partner Violence.
AB  - BACKGROUND: Intimate partner violence (IPV) is common in patients attending
      health-care services and is associated with a range of health problems. The
      majority of IPV perpetrators are men, and a substantial minority of men are
      victims, yet health-care professionals have little evidence or guidance on how to
      respond to male patients who perpetrate or experience violence in their intimate
      relationships. METHODS: We conducted a systematic review to determine the
      effectiveness of interventions for male perpetrators or victims of IPV in health
      settings. Online databases, reference lists, Google Scholar, and gray literature
      were searched, and inclusion/exclusion criteria were applied. Narrative synthesis
      methods were used due to the heterogeneity of study types and outcome measures.
      RESULTS: Fourteen studies describing 10 interventions met our inclusion criteria:
      nine randomized controlled trials, four cohort studies, and one case-control
      study. Interventions were predominantly therapeutic in nature and many were
      conducted in alcohol treatment settings. CONCLUSION: Overall, the evidence for
      effectiveness of interventions in health-care settings was weak, although IPV
      interventions conducted concurrently with alcohol treatment show some promise.
      More work is urgently needed in health-care services to determine what
      interventions might be effective, and in what settings, to improve the response
      to male perpetrators or victims of IPV.

PMID- 29333973
TI  - Facilitators and Barriers to Child Sexual Abuse (CSA) Disclosures: A Research
      Update (2000-2016).
AB  - Identifying and understanding factors that promote or inhibit child sexual abuse
      (CSA) disclosures has the potential to facilitate earlier disclosures, assist
      survivors to receive services without delay, and prevent further sexual
      victimization. Timely access to therapeutic services can mitigate risk to the
      mental health of survivors of all ages. This review of the research focuses on
      CSA disclosures with children, youth, and adults across the life course. Using
      Kiteley and Stogdon's literature review framework, 33 studies since 2000 were
      identified and analyzed to extrapolate the most convincing findings to be
      considered for practice and future research. The centering question asked: What
      is the state of CSA disclosure research and what can be learned to apply to
      practice and future research? Using Braun and Clarke's guidelines for thematic
      analysis, five themes emerged: (1) Disclosure is an iterative, interactive
      process rather than a discrete event best done within a relational context; (2)
      contemporary disclosure models reflect a social-ecological, person-in-environment
      orientation for understanding the complex interplay of individual, familial,
      contextual, and cultural factors involved in CSA disclosure; (3) age and gender
      significantly influence disclosure; (4) there is a lack of a life-course
      perspective; and (5) barriers to disclosure continue to outweigh facilitators.
      Although solid strides have been made in understanding CSA disclosures, the
      current state of knowledge does not fully capture a cohesive picture of
      disclosure processes and pathways over the life course. More research is needed
      on environmental, contextual, and cultural factors. Barriers continue to be
      identified more frequently than facilitators, although dialogical forums are
      emerging as important facilitators of CSA disclosure. Implications for practice
      in facilitating CSA disclosures are discussed with recommendations for future
      research.

PMID- 29333974
TI  - Understanding the Relation Between Neighborhoods and Intimate Partner Violence:
      An Integrative Review.
AB  - Stemming in part from the lack of theory, predictors of the relationship between
      neighborhoods and intimate partner violence (IPV) are underidentified.
      Furthermore, few mediation studies exist that inductively build and deductively
      confirm theoretical frameworks. This article provides an integrative review of
      the literature, aiming to enhance the field's understanding of predictors and
      potential mechanisms that drive this relationship, using a combined theoretical
      model to guide the analysis. The integrative review was conducted using
      Whittemore and Knafl's systematic method for integrative reviews with articles
      published between 1995 and 2015. Findings indicate that macro-, exo-, and
      mesolevel predictors and mediators in the proposed model have modest empirical
      support; however, a number of concepts at each ecological level have yet to be
      fully researched. Results of this review suggest that a well-defined and
      integrative theoretical framework will enhance the current understanding of
      ecological research into IPV. Additionally, a comprehensive ecological approach
      to IPV intervention is likely to be more effective than employing solely an
      individual-level approach. Intervention implications are discussed.

PMID- 29333975
TI  - Toward a Better Understanding of Psychological Symptoms in People Confronted With
      the Disappearance of a Loved One: A Systematic Review.
AB  - OBJECTIVE: The disappearance of a loved one is claimed to be the most stressful
      type of loss. The present review explores the empirical evidence relating to this
      claim. Specifically, it summarizes studies exploring the prevalence and
      correlates of psychological symptoms in relatives of missing persons as well as
      studies comparing levels of psychopathology in relatives of the disappeared and
      the deceased. METHOD: Two independent reviewers performed a systematic search in
      PsychINFO, Web of Science, and Medline, which resulted in 15 studies meeting
      predefined inclusion criteria. Eligible studies included quantitative peer
      reviewed articles and dissertations that assessed psychopathology in relatives of
      missing person. RESULTS: All reviewed studies were focused on disappearances due
      to war or state terrorism. Prevalence rates of psychopathology were mainly
      described in terms of post-traumatic stress disorder and depression and varied
      considerably among the studies. Number of experienced traumatic events and
      kinship to the missing person were identified as correlates of psychopathology.
      Comparative studies showed that psychopathology levels did not differ between
      relatives of missing and deceased persons. CONCLUSIONS: The small number of
      studies and the heterogeneity of the studies limit the understanding of
      psychopathology in those left behind. More knowledge about psychopathology
      postdisappearance could be gained by expanding the focus of research beyond
      disappearances due to war or state terrorism.

PMID- 29333976
TI  - Psychological Trauma in the Context of Familial Relationships: A Concept
      Analysis.
AB  - Many forms of psychological trauma are known to develop interpersonally within
      important relationships, particularly familial. Within the varying theoretical
      constructs of psychological traumas, and distinct from the processes of
      diagnosis, there is a need to refine the scope and definitions of psychological
      traumas that occur within important familial relationships to ensure a cohesive
      evidence base and fidelity of the concept in application to practice. This review
      used a philosophical inquiry methodology of concept analysis to identify the
      definitions, antecedents, characteristics, and consequences of the varying
      conceptualizations of psychological trauma occurring within important
      relationships. Interactions between concepts of interpersonal trauma, relational
      trauma, betrayal trauma, attachment trauma, developmental trauma, complex trauma,
      cumulative trauma, and intergenerational trauma are presented. Understanding of
      the discrete forms and pathways of transmission of psychological trauma between
      individuals, including transgenerationally within families, creates opportunities
      for prevention and early intervention within trauma-focused practice. This review
      found that concepts of psychological trauma occurring within familial
      relationships are not exclusive of each other but overlap in their encompassment
      of events and circumstances as well as the effect on individuals of events in the
      short term and long term. These traumas develop and are transmitted in the space
      between people, both purposefully and incidentally, and have particularly
      profound effects when they involve a dependent infant or child. Linguistic and
      conceptual clarity is paramount for trauma research and practice.

PMID- 29333977
TI  - The Prevalence of Self-Reported Elder Abuse Among Older Women in Community
      Settings: A Systematic Review and Meta-Analysis.
AB  - The abuse of older women appears to be a significant problem. Developing a better
      understanding of the extent of the problem is an important step toward preventing
      it. We conducted a global systematic review and meta-analysis of existing
      prevalence studies, in multiple languages, that occurred in the community
      settings from inception to June 26, 2015, in order to determine the extent of
      abuse against women aged 60 years and over. To disentangle the wide variations in
      prevalence estimates, we also investigated the associations between prevalence
      estimates and studies' demographic and methodological characteristics. A total of
      50 studies were included in the meta-analysis. The combined prevalence for
      overall elder abuse in the past year was 14.1% (95% confidence interval (CI)
      [11.0, 18.0]). Pooled prevalence for psychological abuse was 11.8% (95% CI [9.2%,
      14.9%]), neglect was 4.1% (95% CI [2.7%, 6.3%]), financial abuse was 3.8% (95% CI
      [2.5%, 5.5%]), sexual abuse was 2.2% (95% CI [1.6%, 3.0%]), and physical abuse
      was 1.9% (95% CI [1.2%, 3.1%]). The studies included in the meta-analysis for
      overall abuse were heterogeneous indicating that significant differences among
      the prevalence estimates exist. Significant associations were found between
      prevalence estimates and the following covariates: World Health Organization
      defined regions, countries' income classification, and sample size. Together,
      these covariates explained 37% of the variance. Although robust prevalence
      studies are sparse in low- and middle-income countries, about 1 in 6, or 68
      million older women experience abuse worldwide. More work is needed to understand
      the variation in prevalence rates and implications for prevention.

PMID- 29333978
TI  - The Prevalence of Domestic Violence Among Pregnant Women in Nigeria: A Systematic
      Review.
AB  - OBJECTIVE: To identify, appraise, and synthesize research evidence on the
      prevalence of domestic violence (DV) among pregnant women in Nigeria. METHOD: We
      conducted a systematic review of all published studies between April 2004 and
      June 2016. Comprehensive searches were conducted on electronic databases such as
      PubMed, CINAHL, Global Health, MEDLINE, PsycINFO, Directory of Open Access
      Journals, Google Scholar, and electronic libraries of the authors' institution.
      Identified articles were screened in two stages against the inclusion criteria
      with titles and abstract screened first followed by full-text screening. Selected
      articles were assessed using the "guidelines for evaluating prevalence studies,"
      and findings were synthesized narratively. RESULTS: Among 19 studies that met the
      inclusion criteria, two articles were excluded due to low methodological quality
      and 17 articles were included in the review. The prevalence of DV during
      pregnancy in Nigeria ranged between 2.3% and 44.6% with lifetime prevalence rates
      ranging between 33.1% and 63.2%. Physical, sexual, psychological, and verbal
      abuses were the most frequent types of DV reported in this review. The most
      common perpetrators were husbands, as reported in 11 of the 17 studies. Pregnant
      women between the ages of 20 and 30 years were the most common victims of DV.
      CONCLUSION: Our review suggests high prevalence of DV in pregnancy among women in
      Nigeria and higher lifetime prevalence. However, determining an overall,
      synthesized accurate prevalence rate of DV within this population based on
      existing evidence presents a challenge. The findings have important implications
      for stakeholders such as planners, policy makers, maternity care providers, and
      researchers in public health and social policy at national, regional, and
      international levels toward combating the issue.

PMID- 29333979
TI  - Effect of anoxic to aerobic duration ratios on nitrogen removal and nitrous oxide
      emission in the multiple anoxic/aerobic process.
AB  - Characteristics of nitrogen removal and nitrous oxide (N2O) emission in the
      multiple anoxic/aerobic (AO) process were examined in three sequencing batch
      reactors (SBRs) with different anoxic durations (50 min, SBRH; 40 min, SBRM; 30
      min, SBRL) and a fixed aerobic duration of 30 min. The highest total inorganic
      nitrogen removal percentage of 85.8% was obtained in SBRH, while a minimum N2O
      emission factor of 1.9% was obtained in SBRL. During nitrification batch
      experiments, the N2O emission factor and emission rate were both lower in SBRH
      than SBRL. More N2O production was obtained during denitrification in SBRH when
      denitrifiers utilized intracellular organic carbon. Nitrite reduction by
      heterotrophs was the main N2O production pathway during simultaneous
      nitrification and denitrification in SBRH and SBRL, with the N2O emission factor
      of 31.3% and 36.3%, respectively. Adequate anoxic duration and lowering aerobic
      nitrite concentrations could be adopted to mitigate N2O emission in the multiple
      AO process. The dominant microorganisms at the phylum level in all reactors were
      Proteobacteria and Bacteroidetes, while the abundance of Nitrospira was the
      highest in SBRH with relatively lowest dissolved oxygen concentrations.

PMID- 29333981
TI  - Co-Occurring Substance Use, PTSD, and IPV Victimization: Implications for Female
      Offender Services.
AB  - The co-occurrence of substance use disorders (SUDs) and post-traumatic stress
      disorder (PTSD) among women who have been the victims of intimate partner
      violence (IPV) is complex and causal associations cannot be assumed. Although the
      presence of co-occurring disorders among IPV victims is a well-established
      research finding, there is a need for improved understanding of their prevalence
      and related mental health treatment requirements among female offenders. We
      review research indicating that service providers working with IPV victims can
      expect to encounter women with extensive concurrent problems and examine evidence
      for integrated treatment for SUD, PTSD, and IPV. We propose an outline for
      assessing and treating SUD and PTSD among female offenders who have experienced
      IPV victimization. We intend this review to build on previous calls in the co
      occurring disorders literature and help integrate the research and treatment
      evaluation literatures in a way that points to practical implications for policy
      and practice in female offender services.

PMID- 29333980
TI  - Percentages of PD-1+CD4+T cells and PD-L1+DCs are increased and sPD-1 level is
      elevated in patients with immune thrombocytopenia.
AB  - The present study is to measure the expression of programmed death (PD)-1 /
      programmed death ligand-1 (PD-L1) negative costimulatory molecules, soluble
      format sPD-1 in patients with immune thrombocytopenia (ITP), and to investigate
      their correlation with the secretion of cytokines. A total of 35 patients with
      ITP were included in the present study. Twenty healthy subjects who received
      physical examination at our hospital were included as control group. Peripheral
      blood was collected from all ITP patients and healthy subjects. Flow cytometry
      was performed to determine the percentages of PD-1+CD4+T cells and PD-L1+DCs in
      ITP patients and healthy subjects. Enzyme-linked immunosorbent assay was
      performed to measure the concentrations of interferon (IFN)-gamma, interleukin
      (IL)-17 and sPD-1 in peripheral blood from ITP patients and healthy subjects.
      Percentages of PD-1+CD4+T cells and PD-L1+DCs in peripheral blood from ITP
      patients before treatment were significantly higher than that from healthy
      subjects, but were not different from those after treatment. Serum concentrations
      of IFN-gamma, IL-17 and sPD-1 in ITP patients before treatment were significantly
      higher than those in healthy subjects, and these concentrations were
      significantly reduced after treatment. The concentration of sPD-1 was positively
      correlated with the concentration of IFN-gamma, and negatively correlated with
      platelet count. Percentages of PD-1+CD4+T cells and PD-L1+DCs in ITP patients are
      higher than those in healthy subjects, but elevated sPD-1 concentration in the
      blood blocks PD-1/PD-L1 signaling pathway, leading to unaffected Th cell
      function. Elevated concentrations of IFN-gamma and IL-17 in the blood may
      participate in the occurrence and development of ITP.

PMID- 29333982
TI  - Violence Against Young Women in Non-urban Areas of Australia: A Scoping Review.
AB  - Violence against women is globally prevalent and harmful to women's health and
      well-being. Younger women are at higher risk of abuse, especially those from non
      urban areas who may face specific barriers to disclosure and support. The aim of
      this review was to map the breadth and nature of the "violence against women"
      literature particular to young non-urban Australian women and identify research
      gaps to inform future research with young people. A comprehensive scoping review
      methodology, as outlined by Arksey and O'Malley, was adopted. English language,
      peer-reviewed articles were identified from five databases between January 2000
      and July 2015. Grey literature was also examined. Inclusion criteria for the
      review included young women (15-24 years) from non-urban areas of Australia.
      Twenty-four full-text articles were included in this review. Themes identified
      include prevalence and type of abuse, experiences and response to violence, and
      the consequences of abuse. Recommendations from the review which are relevant to
      a global audience include the need for improved service access, improved data
      collection on the prevalence of violence, and a focus on more research with young
      women in non-urban areas. There is limited research on violence against young
      women living in non-urban areas of Australia. Evidence to date consists of
      predominantly quantitative data generated from general population surveys. There
      is a lack of qualitative research on this topic, and we argue that more is needed
      to gain a better understanding of the violence that young women experience.

PMID- 29333983
TI  - Intimate Partner Violence in Male Survivors of Child Maltreatment: A Meta
      Analysis.
AB  - Intimate partner violence (IPV) is a major public health concern. Yet, despite an
      increasingly extensive literature on interpersonal violence, research on male
      victims of IPV remains sparse and the associations between different forms of
      child maltreatment (CM) and IPV victimization and perpetration in men remains
      unclear. The present meta-analysis evaluated five different forms of CM (sexual,
      physical, and psychological abuses, neglect, and witnessing IPV) as they
      predicted sexual, psychological, and physical IPV perpetration and victimization
      in men. Overall, most available studies examined men as perpetrators of IPV,
      whereas studies of victimization in men were relatively scarce. Results reveal an
      overall significant association ( r = .19) between CM and IPV. The magnitude of
      this effect did not vary as a function of type (perpetration vs. victimization)
      or form (sexual, psychological, or physical) of IPV. Although all forms of CM
      were related to IPV, with effect sizes ranging from .05 (neglect and IPV
      victimization) to .26 (psychological abuse and IPV victimization), these
      associations varied in magnitude according to the type of CM. Findings suggest
      the importance of expanding research on CM and IPV to include a range of
      different kinds of abuse and neglect and to raise concerns about the experience
      of men as both victims and perpetrators of IPV.

PMID- 29333984
TI  - A Methodological Review and Critique of the "Intergenerational Transmission of
      Violence" Literature.
AB  - Exposure to interpersonal or interparental violence (EIPV) and child abuse and
      maltreatment (CAM) are associated with an increased risk of maladaptive outcomes,
      including later involvement in adulthood intimate partner violence (IPV; often
      referred to as the theory of intergenerational transmission of violence). Recent
      meta-analyses, however, have documented a weak effect size when examining this
      association. By focusing on young adulthood, a development stage in which
      identity development and romantic relationship formation are salient tasks, we
      can provide insight into the association between EIPV, CAM, and IPV. Guided by
      the methodological critiques from the IPV and EIPV literatures, the present study
      reviewed the methodology used in 16 studies (published between 2002 and 2016)
      that tested the theory of intergenerational transmission of violence. The review
      study focused on how EIPV, CAM, and young adult dating violence were measured and
      analyzed, with the initial goal of better understanding how methodological
      decision informed the study's findings. Ultimately, we determined that there was
      simply too much methodological variability and yet too little methodological
      complexity to truly inform a review and discussion of the results; therefore, our
      review solely focused on the study's methodological decisions. Based on our
      review, we suggest that both of these challenges, too much variability and too
      little complexity, hinder our ability to examine the theory of intergenerational
      transmission of violence. Future research must strike a balance between
      methodological consistency and complexity to better understand the intricate
      nuances of IPV experiences and inform practice.

PMID- 29333985
TI  - A Systematic Review of Interventions for Women Parenting in the Context of
      Intimate Partner Violence.
AB  - Intimate partner violence (IPV) victimization is widespread among women with
      children and has negative consequences for both women's and children's well
      being. Despite mixed evidence regarding the effect of IPV on women's parenting
      ability and behaviors, there is an increasing focus on mothering in the context
      of IPV, particularly among the child welfare and child protection systems. To
      help respond to this increasing focus, several interventions have been developed
      that specifically target parenting among IPV-affected women. Given the growing
      numbers of these interventions, a comprehensive review is needed to help
      elucidate the approaches that are most effective in meeting the needs of IPV
      affected women and children. Therefore, we conducted an in-depth systematic
      review of the literature to examine the approaches and effects of interventions
      designed to address aspects of parenting among IPV-affected women. We identified
      26 articles concerned with 19 distinct interventions for review. We found
      substantial heterogeneity in intervention delivery, format, length, and focus. We
      noted several limitations of the existing studies in terms of study sample,
      measures, design, and implementation. Given the heterogeneity of the existing
      interventions and the limitations of the current research base, it is not yet
      clear which interventions or intervention components are most effective in
      addressing the unique needs of women parenting in the context of IPV. Further
      research is needed to address these limitations, and professionals working with
      IPV-affected families should be aware that current services may not meet women's
      and children's needs.

PMID- 29333986
TI  - The Prevalence and Correlates of Partner Violence Used and Experienced by Adults
      With Intellectual Disabilities: A Systematic Review and Call to Action.
AB  - It has been suggested that individuals with intellectual disabilities (IDs) are
      at increased risk of violence perpetration and victimization. A systematic review
      was undertaken to identify and critically evaluate the existing empirical
      research concerning the use and experience of partner violence by adults with
      IDs. In total, six poor-quality articles were identified: five of which adopted
      qualitative methods and one of which adopted a mixed-methods approach, comprising
      a total of 93 participants (48 women, 45 men: 1 perpetrator, 92 victims). The
      qualitative data were extracted from the studies and synthesized. A partner
      violence victimization rate of 60% was identified in one nonrepresentative
      sample. Two superordinate themes emerged from the qualitative data: nature of
      partner violence experience and help seeking. Children were the cross-cutting
      theme within the two superordinate themes. Participants reported experiencing a
      range of physical, emotional, and sexual violence leading to serious injury and
      psychological consequences. Participants reported experiences of positive and
      negative help-seeking reactions from professionals and specific requirements of
      services for victims with IDs. Children were identified as involved in the
      experience of abuse, the impact of abuse, and decisions to seek help. The
      findings indicate that training of clinical staff to detect partner violence is
      needed. In addition, adults with IDs need education concerning healthy
      relationships. Research is needed to better understand the difference between
      "challenging behavior" that is behavior displayed by an individual which
      challenges services, family members, and carers. Such behavior is more common in
      individuals with a severe ID for whom it would not be appropriate to be dealt
      with through the criminal justice system, and partner violence, in order to
      develop appropriate interventions for victims and perpetrators with ID.

PMID- 29333987
TI  - Comparing Long-Term Placement Outcomes of Residential and Family Foster Care: A
      Meta-Analysis.
AB  - This study presents findings from three separate meta-analyses investigating
      differences between children placed in residential care and in family foster care
      with regard to three outcomes: internalizing behaviors, externalizing behaviors,
      and perception of care. Based on publications from the last 20 years, a total of
      23 studies were included. The total sample consisted of 13,630 children in care,
      with 7,469 from foster care and 6,161 from residential care. The results from
      this study indicated that children in foster care had consistently better
      experiences and less problems across the three outcomes as compared to children
      in residential care. Analyses did not reveal evidence of publication bias, and
      sensitivity analyses also suggested that results were not influenced by
      individual studies. Additionally, moderation analyses revealed that the
      differences between foster and residential care could vary depending on certain
      factors such as the publication year, the gross domestic product of the country,
      and the length of care. The implications of differences in outcomes between the
      two placements are discussed.

PMID- 29333988
TI  - Male IPV Perpetrator's Perspectives on Intervention and Change: A Systematic
      Synthesis of Qualitative Studies.
AB  - OBJECTIVE: To add to our understanding of change processes by analyzing
      perpetrators' perspectives on intervention. METHOD: Fourteen databases were
      searched and 27 articles reporting relevant qualitative findings were identified.
      Analytic coding was applied across the findings and discussion sections of all 27
      study reports to form an interpretive account of the data set. Studies were also
      grouped according to their perceived theoretical standpoints, and a summary of
      themes in each grouping is presented. FINDINGS: Study participants were largely
      positive about their experiences in intervention; new learning such as conflict
      interruption techniques and new communication skills were commonly cited
      benefits. Perpetrators attend perpetrator intervention programs with a range of
      motivations, ranging from a determination to change who they are, to a
      determination to avoid a custodial sentence. The most common barriers to change,
      found in this analysis, were cognitive distortions, emotional dysregulation,
      gendered social constructions, and self-esteem issues. CONCLUSION: Further
      qualitative investigation, of rigor, with the intention-to-treat population of
      intimate partner violence perpetrators involved in perpetrator programs is
      needed. At this point, we would venture that qualitative research, with
      perpetrators, underlines the precept that formidable barriers to change exist in
      this population. The centrality of group work to perpetrator interventions should
      be reconsidered in light of the complexity of the change task and in light of the
      heterogeneity of this population.

PMID- 29333989
TI  - Sexual Violence Victimization Among College Females: A Systematic Review of
      Rates, Barriers, and Facilitators of Health Service Utilization on Campus.
AB  - To date, little work specifically addresses empirical studies concerning barriers
      and facilitators to health service use among college female sexual violence
      victims. The following objectives were addressed: (1) analyze studies of college
      aged women who have been victims of sexual violence to examine the frequency and
      moderating characteristics of utilization of university-based resources
      available, (2) identify inconsistencies and gaps in the literature concerning
      sexual victimization and service utilization, and (3) provide next steps for
      researchers and clinical care coordinators. Six electronic databases were
      searched from 1990 to May 2016. Inclusion criteria for the review were (1)
      university or college setting or sample, (2) empirical design, and (3) inclusion
      of some discussion or measurement of health service use. Following preferred
      reporting items for systematic reviews and meta-analyses (PRISMA) procedures, 22
      articles were identified for the review. Although prevalence rates of sexual
      victimization were high (4.7-58%), rates of service utilization were lower (0
      42%). There were significant discrepancies between hypothetical use of services
      and actual rates of service use. Identified barriers included feelings of shame,
      guilt and embarrassment, not wanting friends and family to find out, and thinking
      the victimization was not serious enough to report. Identified facilitators
      included acknowledging the sexual violence victimization as a crime, receiving
      encouragement from friends and family to utilize health services, and receiving a
      positive response during the initial informal disclosure. Finally, measurement of
      victimization was inconsistent across studies. Recommendations are offered for
      college campus prevention programming and future research.

PMID- 29333990
TI  - Child Sexual Abuse: Toward a Conceptual Model and Definition.
AB  - The problem of defining "child sexual abuse" (CSA), and the need to define this
      concept, has been recognized by major policy bodies and leading researchers since
      the 1970s. Recent demands for a more theoretically robust, explicit definition of
      CSA show this challenge remains urgent. In this article, we identify problems
      caused by variance in definitions of CSA for five domains: research and knowledge
      formation, legal frameworks and principles, prevention efforts, policy responses,
      and the establishment of social norms. We review and analyze definitions used in
      leading international epidemiological studies, national and international policy
      documents, social science literature, and legal systems in the United States,
      Canada, and Australia to demonstrate the continuing use of different concepts of
      CSA and identify key areas of conceptual disagreement. Informed by our literature
      review, we use a methodology of conceptual analysis to develop a conceptual model
      of CSA. The purpose of this model is to propose a more robust, theoretically
      sound concept of CSA, which clarifies its defining characteristics and
      distinguishes it from other concepts. Finally, we provide operational examples of
      the conceptual model to indicate how it would translate to a classificatory
      framework of typologies of acts and experiences. A sound conceptual model and
      classificatory system offers the prospect of more appropriate and effective
      methods of research, response, regulation, and prevention. While total consensus
      is unattainable, this analysis may assist in developing understanding and
      advancing more coherent approaches to the conceptual foundation of CSA and its
      operationalization.

PMID- 29333991
TI  - Evaluation of a portable gas chromatograph with photoionization detector under
      variations of VOC concentration, temperature, and relative humidity.
AB  - The objective of this present study was to evaluate the performance of a portable
      gas chromatograph-photoionization detector (GC-PID), under various test
      conditions to determine if it could be used in occupational settings. A mixture
      of 7 volatile organic compounds (VOCs)-acetone, ethylbenzene, methyl isobutyl
      ketone, toluene, m-xylene, p-xylene, and o-xylene-was selected because its
      components are commonly present in paint manufacturing industries. A full
      factorial combination of 4 concentration levels (exposure scenarios) of VOC
      mixtures, 3 different temperatures (25 degrees C, 30 degrees C, and 35 degrees
      C), and 3 relative humidities (RHs; 25%, 50%, and 75%) was conducted in a full
      size controlled environmental chamber. Three repetitions were conducted for each
      test condition allowing for estimation of accuracy. Time-weighted average
      exposure data were collected using solid sorbent tubes (Anasorb 747, SKC Inc.) as
      the reference sampling medium. Calibration curves of Frog-4000 using the dry
      gases showed R2 > 0.99 for all analytes except for toluene (R2 = 0.97). Frog-4000
      estimates within a test condition showed good consistency for the performance of
      repeated measurement. However, there was ~41-64% reduction in the analysis of
      polar acetone with 75% RH relative to collection at 25% RH. Although Frog-4000
      results correlated well with solid sorbent tubes (r = 0.808-0.993, except for
      toluene) most of the combinations regardless of analyte did not meet the <25%
      accuracy criterion recommended by NIOSH. The effect of chromatographic co-elution
      can be seen with m, p-xylene when the results are compared to the sorbent tube
      sampling technique with GC-flame ionization detector. The results indicated an
      effect of humidity on the quantification of the polar compounds that might be
      attributed to the pre-concentrator placed in the selected GC-PID. Further
      investigation may resolve the humidity effect on sorbent trap with micro GC pre
      concentrator when water vapor is present. Although this instrument does not
      fulfill the accuracy criterion specified in the NIOSH technical report No. 2012
      162, it can be used as a screening tool for range finding monitoring with dry
      gases calibration in the occupational setting rather than compliance monitoring.

PMID- 29333992
TI  - Insecure Adult Attachment and Child Maltreatment: A Meta-Analysis.
AB  - Extant evidence has shown that insecure adult attachment is related to
      dysfunctional parenting styles that heighten parents' risk of child maltreatment.
      However, there is a lack of studies appraising the evidence for the association
      between insecure adult attachment and child maltreatment. This meta-analytic
      study examined the relationship between parents' adult attachment and child
      maltreatment perpetration/child abuse potential. Studies examining the
      relationship between parents' adult attachment and child maltreatment/child abuse
      potential published before February 2017 were identified through a systematic
      search of online databases. In total, 16 studies ( N = 1,830) were selected. Meta
      analysis based on random-effects models shows a significant positive association
      between insecure attachment and child maltreatment (pooled effect size: odds
      ratio [ OR] = 2.93, p = .000). Subgroup analyses show insecure attachment was
      more strongly associated with failure to thrive ( OR = 8.04, p = .000) and
      filicide ( OR = 5.00, p < .05). Medium effect sizes were found for subgroup
      analyses on insecure romantic attachment ( OR = 3.76, p = .000), general
      attachment ( OR = 3.38, p = .000), attachment to own child ( OR = 3.13, p =
      .001), and to own parents ( OR = 2.63, p = .000) in relation to child
      maltreatment.

PMID- 29333993
TI  - History of environmental and occupational health.

PMID- 29333994
TI  - The Association Between Serious Mental Health Problems and Violence: Some Common
      Assumptions and Misconceptions.
AB  - The media, the general public, and politicians often emphasize that mental
      illness is a precursor and a cause of violence, particularly emphasizing an
      assumed relationship between mental illness, including psychopathy and psychosis,
      and the use of guns to commit violence. We report which individuals with serious
      mental health problems have an increased risk to commit violence (including gun
      violence). Second, we answer the question to what extent serious mental health
      problems explain most violence and especially gun-related violence. And what is
      the opinion of experts on these questions? Third, we review which effective
      screening instrument can help to identify individuals with mental health problems
      who are at risk to carry a gun and commit violence. For policy makers and
      legislators, this article points out that most psychiatric disorders are not
      related to violence, with some exceptions such as schizophrenia and bipolar
      disorder, and often only in conjunction with substance use. We show that the
      attributable risk of mental illness to explain violence in general is low. We
      also emphasize that conduct disorder in late childhood or adolescence is a better
      predictor of violence than is mental illness at a later age. Empirically based
      screening methods to identify individuals with mental health problems who are
      prone to violence appear to have limited utility. Implications are discussed for
      clinicians and practitioners working in the justice system, researchers, and
      policy makers.

PMID- 29333995
TI  - Violence Against International Students: A Critical Gap in the Literature.
AB  - Despite the growing trend on college campuses to increase their international
      student body, this population is largely left out of research due to the
      complexity they bring to the research process compared to their domestic
      counterparts. This is particularly true for the existing research on campus
      sexual violence; thus, there is no research-based indication that international
      students, let alone international graduate students, would face victimization
      risks on campus in the same way the extant literature identifies for domestic
      undergraduates. The existing research on international students indicates that
      their experiences are different than their domestic counterparts, and the sparse
      literature on graduate students indicates their experiences are different from
      their undergraduate counterparts. A specific focus on the intersection of these
      two identities, international graduate students, is almost completely absent from
      the literature. This research review highlights key research that provides
      foundational knowledge for the experience of international students and
      international graduate students with regard to their vulnerability to sexual
      violence. The author organizes the extant literature into three major areas that
      inform the overarching research topic: (1) international student experiences, (2)
      victimization, and (3) campus culture. Basic findings indicate that there are
      limitations in extrapolating previous research findings on campus sexual violence
      to this population, calling for a need to focus specifically and intentionally on
      this population of students. The objective of this article is to review the
      current state of knowledge about the risk and vulnerability of international
      students to sexual violence and victimization and to address the directions for
      future research.

PMID- 29333996
TI  - Energy Expenditure and Intensity of Active Video Games in Children and
      Adolescents.
AB  - PURPOSE: This study aimed to compare the energy expenditure and intensity of
      active video games to that of treadmill walking in children and adolescents.
      METHOD: Seventy-two boys and girls (aged 8-13 years) were recruited from local
      public schools. Energy expenditure and heart rate were measured during rest,
      during 3-km/hr, 4-km/hr, and 5-km/hr walks, and during active games (Adventure,
      Boxing I, Boxing II, and Dance). During walking and active games, we also
      assessed physical activity using an accelerometer. RESULTS: The energy
      expenditure of the active games Adventure, Boxing I, Boxing II, and Dance was
      similar to that of treadmill walking at 5 km/hr in boys and girls. Heart rate was
      significantly higher for the game Adventure compared with walking at 3 km/hr, 4
      km/hr, and 5 km/hr and the game Dance in both genders. The heart rate of girls
      during the games Adventure and Dance was significantly higher compared with boys.
      There was a statistically significant difference (p < .05, with an effect size
      ranging from 0.40 to 3.54) in the counts.min-1, measured through accelerometry,
      between activities. CONCLUSION: XBOX 360 Kinect games provide energy expenditure
      and physical activity of moderate intensity for both genders. The use of active
      video games can be an interesting alternative to increase physical activity
      levels.

PMID- 29333997
TI  - Understanding the Relationship Between Male Gender Socialization and Gender-Based
      Violence Among Refugees in Sub-Saharan Africa.
AB  - Gender-based violence (GBV) in humanitarian emergencies is progressively
      recognized as a global public health problem. Detrimental gender norms influence
      male perpetrated GBV against women, and social and structural contexts of forced
      migration and camp resettlement contribute to problematic gender norm
      development. The review sought to elucidate the dynamics that link gender
      socialization among male youth in sub-Saharan Africa with violent sexual
      behaviors. Two concepts were explored: (1) male gender socialization in sub
      Saharan Africa related to GBV perpetration patterns and (2) the effect of forced
      migration on male socialization and GBV. We reviewed articles using a standard
      systematic review methodology, searching academic databases for peer-reviewed
      articles, and contacting experts for gray literature. Our initial search
      identified 210 articles. We manually reviewed these, and 19 met the review
      inclusion criteria. We identified 20 variables from the first concept and 18
      variables from the second. GBV perpetration by male youth is positively
      associated with social pressures as well as cultural and religious beliefs. Amid
      forced migration, personal, societal, and cultural preexisting gender
      inequalities are often amplified to encourage GBV perpetration. The literature
      revealed aspects of culture, language, role modeling, religion, and the context
      of violence as important factors that shape young men's perspectives regarding
      the opposite sex and gender relations as well as sexual desires and dominance.
      Overall, though, literature focusing on male socialization and GBV prevention is
      limited. We made recommendations for future studies among refugee male youth in
      order to better understand these relationships.

PMID- 29333998
TI  - When Older People Are Violent or Abusive Toward Their Family Caregiver: A Review
      of Mixed-Methods Research.
AB  - What happens when family caregivers experience violence and abuse from the older
      person for whom they care? Although this issue has received little global
      attention, it is relevant to researchers, practitioners, and policy makers
      working across the intersecting fields of older age care and medicine, adult
      protection and safeguarding, and domestic and intimate partner violence. To date,
      these fields have generated diverse explanations of violence and abuse in older
      age illness and how best to respond to it. This article reports the findings of a
      systematic literature review of 18 quantitative, qualitative, and mixed-methods
      studies that investigated violent and abusive behavior by older people toward
      their family caregivers. The review identified three central themes in the
      literature: (1) There are inconsistent definitions and measurements used in
      research about harmful, violent, and abusive behavior toward family caregivers.
      (2) Violent and abusive behavior toward caregivers is a sensitive and hidden
      topic that poses practical and methodological challenges for researchers. (3)
      There is some evidence to suggest that people who were violent and abusive in
      their earlier life-or who had a poor relationship with their family member in the
      past-are more likely to continue to experience violence and abusive behavior in
      later life. There were two central ways in which violence and abuse were
      conceptualized and investigated: as a "symptom of illness" or as an "act of
      abuse" and we present a visual map of the relationship between these two
      conceptualizations drawn from our analysis of the literature. We conclude by
      discussing the implications of the findings and recommend future directions for
      practice, research, and policy to support affected families.

PMID- 29333999
TI  - Consequences of Elder Abuse and Neglect: A Systematic Review of Observational
      Studies.
AB  - This article presents the results of a systematic review of the consequences of
      elder abuse and neglect (EAN). A systematic search was conducted in seven
      electronic databases and three sources of gray literature up to January 8, 2016,
      supplemented by scanning of citation lists in relevant articles and contact with
      field experts. All observational studies investigating elder abuse as a risk
      factor for adverse health outcomes, mortality, and health-care utilization were
      included. Of 517 articles initially captured, 19 articles met our inclusion
      criteria and were analyzed. Two reviewers independently performed abstract
      screening, full-texts appraisal, and quality assessment using the Newcastle
      Ottawa Scale. Across 19 studies, methodological heterogeneity was a prominent
      feature; seven definitions of EAN and nine measurement tools for abuse were
      employed. Summary of results reveals a wide range of EAN outcomes, from premature
      mortality to increased health-care consumption and various forms of physical and
      psychological symptoms. Higher risks of mortality emerged as the most credible
      outcome, while the majority of morbidity outcomes originated from cross-sectional
      studies. Our findings suggest that there is an underrepresentation of older
      adults from non-Western populations and developing countries, and there is a need
      for more population-based prospective studies in middle- and low-income regions.
      Evidence gathered from this review is crucial in upgrading current practices,
      formulating policies, and shaping the future direction of research.

PMID- 29334000
TI  - Predictors of Interpersonal Violence in the Household in Humanitarian Settings: A
      Systematic Review.
AB  - Interpersonal violence against women and children has increasingly been
      recognized as a public health priority in humanitarian emergencies. However,
      because the household is generally considered a private sphere, violence between
      family members remains neglected. A systematic literature review was conducted to
      identify predictors of household violence in humanitarian emergencies. PubMed,
      Web of Science, and Scopus were searched from January 1, 1998, to February 16,
      2016. A predictor was defined as any individual, household, or community-level
      exposure that increases or decreases the risk associated with physical, sexual,
      or emotional interpersonal violence between two or more people living together.
      All studies reporting on quantitative research were eligible for inclusion.
      Results were analyzed using qualitative synthesis. Preferred Reporting Items for
      Systematic Reviews and Meta-Analyses guidelines were followed as applicable. The
      search strategy resulted in 2,587 original records, of which 33 studies met
      inclusion criteria. Thirty-two of the 33 studies used a cross-sectional design.
      This was the first known systematic review of predictors of household violence in
      humanitarian settings. The household framework drew attention to several factors
      that are associated with violence against both women and children, including
      conflict exposure, alcohol and drug use, income/economic status, mental
      health/coping strategies, and limited social support. There is a need for
      longitudinal research and experimental designs that can better establish
      temporality between exposures and household violence outcomes, control for
      confounding, and inform practice. In the interim, programmers and policy makers
      should try to leverage the predictors identified by this review for integrated
      violence prevention and response strategies, with the important caveat that
      ongoing evaluation of such strategies is needed.

PMID- 29334001
TI  - Integrated Multicomponent Interventions for Safety and Health Risks Among Black
      Female Survivors of Violence: A Systematic Review.
AB  - The epidemic of violence disproportionately affects women, including Black women.
      Black women survivors of violence have been found to face multiple safety and
      health issues such as depression, post-traumatic stress disorder, HIV, and poor
      reproductive health. Many health issues co-occur, and this co-occurrence can be
      associated with additional safety and health-related challenges for survivors.
      Consequently, there is a need for multicomponent interventions that are designed
      to concurrently address multiple health issues commonly faced by Black survivors
      of violence. This systematic review of literature determines the efficacy of
      various strategies used in the existing evidence-based multicomponent
      interventions on violence reduction, promotion of reproductive health, reduction
      in risk for HIV, reduction in levels of stress, and improvement in mental health.
      Sixteen intervention studies were identified. Examples of components found to be
      efficacious in the studies were safety planning for violence, skill building in
      self-care for mental health, education and self-regulatory skills for HIV,
      mindfulness-based stress reduction for reducing stress, and individual counseling
      for reproductive health. Although some strategies were found to be efficacious in
      improving outcomes for survivors, the limitations in designs and methods, and
      exclusive focus on intimate partner violence calls for more rigorous research for
      this population, particularly for Black survivors of all forms of violence. There
      is also need for culturally responsive multicomponent interventions that account
      for diversity among Black survivors.

PMID- 29334002
TI  - Concordance Between Parents in Perpetration of Child Mistreatment: How Often Is
      It by Father-Only, Mother-Only, or by Both and What Difference Does It Make?
AB  - Research on child mistreatment tends to focus on the mother or the father as the
      abusing parent, even though there is wide agreement that both theory and practice
      should deal with child maltreatment as a family system problem. Most children
      have the benefit or the risk of more than one caretaker for substantial periods
      of their lives, most often two parents or stepparents. This article is intended
      to illustrate the value of research which uses concordance analysis (CA) to
      identify children who experienced three dyadic concordance types (DCTs) of
      mistreatment: father-only, mother-only, or both parents, including single-parent
      combinations of caretakers. A concordance approach that identifies possible
      abusers in addition to the presenting parent using the three DCTs is a practical
      first step toward a family system perspective to enhance child abuse theory,
      research, and practice.

PMID- 29334003
TI  - Removing Firearms From Those Prohibited From Possession by Domestic Violence
      Restraining Orders: A Survey and Analysis of State Laws.
AB  - Under federal and many state laws, persons under domestic violence restraining
      orders (DVROs) are prohibited from possession of firearms. Using multiple sources
      and a Lexis Nexis search, we developed a list of state laws pertaining to the
      relinquishment or removal of firearms from persons prohibited from possession by
      DVROs. After downloading the text of each law, we conducted a legal analysis to
      enumerate provisions of the laws specifying implementation. We found 49 laws in
      29 states and Washington, DC. The laws were conceptualized as instructions to the
      court, the respondent, and law enforcement. We detail the content of each state's
      law, including such elements as whether it applies to ex parte DVROs; whether
      certain criteria must be met, such as previous use of a firearm in domestic
      violence or lack of an employment exemption, before the law can be applied; and
      whether the application of the law is mandatory. We also detail instructions to
      the respondent regarding to whom firearms may be relinquished, whether the
      respondent must seek permission to transfer the firearm to a third party, and the
      time by which dispossession must occur. Finally, whether law enforcement bears
      the responsibility for removing the firearm or whether the law gives the court
      the authority to order a search and seizure for the firearms is discussed. The
      purpose of the research is to provide an overview of these state laws that can be
      used by key stakeholders in legislative, judicial, advocacy, or research roles.
      Implications are discussed.

PMID- 29334004
TI  - Examining residence status as a risk factor for health risk behaviors among
      college students.
AB  - OBJECTIVE: The current study is aimed to evaluate college student residence as a
      unique risk factor for a range of negative health behaviors. PARTICIPANTS: We
      examined data from 63,555 students (66% females) from 157 campuses who completed
      the National College Health Assessment Survey in Spring 2011. METHODS:
      Participants answered questions about the frequency of recent use of alcohol,
      tobacco, marijuana, and illicit drugs, as well as sexual risk behavior in the
      last 30 days. Sexual risk behaviors were operationalized as having unprotected
      vaginal sex (yes/no) and the number of sexual partners. RESULTS: Logistic
      regression analyses revealed that living off-campus is a unique predictor of
      alcohol, tobacco, marijuana, and illicit drug use, as well as engaging in
      unprotected sex and a greater number of sexual partners (all ps <. 01).
      CONCLUSIONS: Students living off-campus exhibit more substance use and sexual
      risk behaviors than students living on-campus, independent of gender, age, or
      race.

PMID- 29334006
TI  - The Intersection of Firearms and Intimate Partner Homicide in 15 Nations.
AB  - Intimate partners commit approximately one in three homicides against women
      worldwide. Little is known about situational factors that contribute to intimate
      partner homicides (IPH) and how they may differ across nations. This article
      provides a cross-national exploration of one situational factor, the use of
      firearms in the commission of homicides, and considers whether nations have laws
      designed specifically to keep firearms out of the hands of batterers. We
      conducted a systematic search of peer-reviewed research and governmental and
      nongovernmental reports for data on weapon use in IPH. Data were located for 15
      nations and subnational areas, which varied from firearms being involved in no
      IPHs in Fiji to 59% in Antalya, Turkey. Seven nations have legislation that
      addresses gun ownership as it relates to those who have been charged with,
      convicted of, or show a propensity toward the commission of intimate partner
      violence. These laws vary in whether domestic violence is a factor considered in
      whether to allow firearm ownership or whether it served to disqualify ownership.
      Due to the small number of nations for which data on weapon use in IPH were
      located, we did not conduct any hypothesis testing. There is a need for detailed
      homicide surveillance systems among nations so that researchers can explore the
      epidemiology of these homicides and ultimately identify opportunities for
      intervention.

PMID- 29334005
TI  - Physiological Correlations With Short, Medium, and Long Cycling Time-Trial
      Performance.
AB  - PURPOSE: Several studies have demonstrated that physiological variables predict
      cycling endurance performance. However, it is still unclear whether the
      predictors will change over different performance durations. The aim of this
      study was to assess the correlations between physiological variables and cycling
      time trials with different durations. METHODS: Twenty trained male cyclists
      (maximal oxygen uptake [VO2max] = 60.5 +/- 5.6 mL/kg/min) performed 4 separate
      experimental trials during a 2-week period. Cyclists initially completed an
      incremental exercise test until volitional exhaustion followed by 3 maximal
      cycling time trials on separate days. Each time trial consisted of 3 different
      durations: 5 min, 20 min, and 60 min performed in a randomized order. RESULTS:
      The main results showed that the physiological measures strongly correlated with
      long cycling performances rather than short and medium time trials. The time
      trial mean power output was moderately high to highly correlated with peak power
      output and VO2max (r = .61-.87, r = .72-.89, respectively), and was moderately to
      highly correlated with the lactate threshold Dmax method and second ventilatory
      threshold (r = .52-.75, r = .55-.82, respectively). CONCLUSIONS: Therefore,
      trained cyclists should develop maximal aerobic power irrespective of the
      duration of time trial, as well as enhancements in metabolic thresholds for long
      duration time trials.

PMID- 29334007
TI  - Understanding (and Acting On) 20 Years of Research on Violence and LGBTQ +
      Communities.
AB  - Questions related to violence, vulnerability, and sexual and gender minorities
      continuing to occupy a focal place in U.S. public discourse. We reviewed findings
      from 20 years of research on that topic to make recommendations for policy,
      practice, and future research. This article synthesizes findings from 102 peer
      reviewed articles as well as a small number of unpublished studies and grey
      literature. We found no data to support the idea (widespread in popular
      discourse) that those in the sexual or gender majority require protection from
      sexual or gender minority individuals. Instead, this wide body of research
      indicates that sexual and gender minorities are themselves at elevated risk for
      physical and sexual assault, harassment, bullying, and hate crime victimization
      throughout childhood, adolescence, and adulthood. Contradicting the image of hate
      crimes as perpetrated by strangers or acquaintances, we find that bias-related
      verbal abuse, physical, and sexual assault by close family members contribute
      heavily to observed victimization rates. Further, despite the perception that
      society is becoming more welcoming, victimization disparities appear to be stable
      or widening since the 1990s. More studies with probabilistic sampling approaches,
      standardized measures, and larger samples of gender minorities are needed.
      However, widespread victimization of sexual and gender minorities is clearly an
      urgent issue, demanding attention from clinicians, program developers, and policy
      makers.

PMID- 29334008
TI  - Who Are the Victims and Who Are the Perpetrators in Dating Violence?: Sharing the
      Role of Victim and Perpetrator.
AB  - BACKGROUND: Dating violence (DV) is a serious problem with devastating
      consequences. Often, research on DV has focused on two distinct groups: victims
      and perpetrators. However, there is growing evidence for a victim-perpetrator
      overlap model, which posits that those involved in DV are more likely to take on
      both roles, rather than either role on its own. PURPOSE: We investigated the
      patterns of involvement in DV among those who identified themselves as victims or
      perpetrators in previous studies. METHOD: This was a systematic review and meta
      analysis. A total of 371 variables related to participants' previous and
      concurrent experiences of DV victimization or perpetration (202 variables related
      to victimization and 169 related to perpetration) were identified in 25 studies,
      which were found by systematically searching three databases: PubMed, Web of
      Science, and SCOPUS. RESULTS: The majority of previous studies categorized study
      participants as either DV victims or perpetrators; however, those who identified
      themselves as either DV victims or DV perpetrators were more likely to assume the
      opposite role as well. Specifically, current DV perpetrators had a strong
      association with previous or concurrent victimization experiences, and current DV
      victims were similarly likely to have assumed the roles of both victim and
      perpetrator in their histories. CONCLUSION: Further efforts should be put into
      avoiding categorization of those involved in violence; rather, they should be
      regarded as a single group. Additionally, evidence-based interventions should be
      developed for this population to help break the cycle of violence.

PMID- 29334009
TI  - Perspectives in obesity and pregnancy.
AB  - Obesity is currently recognized as a health epidemic worldwide. Its prevalence
      has doubled in the last three decades. Obesity is a complex clinical picture
      associated with physical, physiologic, hormonal, genetic, cultural, socioeconomic
      and environmental factors. The rate of obesity is also increasing in the pregnant
      women population. Maternal obesity is associated with less than optimal
      obstetrical, fetal and neonatal outcomes. It is also associated with significant
      adverse long-term effects on both obese parturients and the infants born from
      obese women. A number of guidelines have been published to educate health care
      workers and the general population in an attempt to develop effective
      interventions on a large scale to prevent obesity. These guidelines are multiple,
      confusing and inconsistent. There are no standard recommendations regarding
      gestational weight gaining goals, nutrients and additional elements necessary for
      certain obese women who have been treated with bariatric surgical procedures,
      screening for metabolic diseases such as diabetes, additional preventive health
      care services indicated for obese women in the pregnancy planning stages, during
      prenatal care, in the immediate post-partum period and as a long-term approach
      for health preservation. In 2013, the American Medical Association supported by
      several US national medical specialty organizations published Resolution 420 (A
      13) recognizing obesity as a disease state with multiple pathophysiological
      aspects requiring a range of interventions to improve its prevention and
      treatment. The goal of this decision was to encourage a broader spectrum of
      health care benefits insurance coverage for the prevention and treatment of
      obesity. There are a number of myths and misconceptions associated with obesity.
      These perspectives present our views and clinical experience with a partial
      review of recent bibliography addressing the associations between obese
      reproductive age women and their risks during pregnancy.

PMID- 29334012
TI  - Better Together? A Review of Evidence for Multi-Disciplinary Teams Responding to
      Physical and Sexual Child Abuse.
AB  - Multi-Disciplinary teams (MDTs) have often been presented as the key to dealing
      with a number of intractable problems associated with responding to allegations
      of physical and sexual child abuse. While these approaches have proliferated
      internationally, researchers have complained of the lack of a specific evidence
      base identifying the processes and structures supporting multi-disciplinary work
      and how these contribute to high-level outcomes. This systematic search of the
      literature aims to synthesize the existing state of knowledge on the
      effectiveness of MDTs. This review found that overall there is reasonable
      evidence to support the idea that MDTs are effective in improving criminal
      justice and mental health responses compared to standard agency practices. The
      next step toward developing a viable evidence base to inform these types of
      approaches seems to be to more clearly identify the mechanisms associated with
      effective MDTs in order to better inform how they are planned and implemented.

PMID- 29334010
TI  - Esmya(r) and the PEARL studies: A review.
AB  - Ulipristal acetate was investigated in four phase 3 trials. In PEARL I,
      ulipristal produced significant normalisation of blood loss within 1 week and
      decreased fibroid volume. In PEARL II, ulipristal produced faster and more
      consistent control of bleeding than leuprorelin acetate and had a more favourable
      side-effect profile. Ulipristal-induced decreases in fibroid volume persisted for
      6 months, whereas fibroids regrew after leuprorelin was stopped. PEARL III showed
      that ulipristal was effective during long-term treatment, with norethisterone
      further reducing the magnitude of bleeding in the off-treatment period. PEARL IV
      investigated ulipristal over four cycles, finding little difference between 5 and
      10 mg ulipristal, further changes in menstruation and fibroid volume with repeat
      courses, and no increase in side effects.

PMID- 29334011
TI  - A qualitative study of cervical cancer and cervical cancer screening awareness
      among nurses in Ghana.
AB  - Despite the availability of cervical cancer screening tools, including those that
      are appropriate for low resource settings, the rates of preventive cervical
      cancer screening remain extremely low among women in LMICS. Nurse-led education
      interventions have been proven to be effective at increasing participation in
      healthcare recommendations. However, there is a need to determine nurses'
      knowledge of cervical cancer and cervical cancer prevention in order to develop
      effective health education interventions. Our goal was to assess Ghanaian nurses'
      knowledge of cervical cancer and cervical cancer prevention. Interviews and small
      focus groups were conducted with 42 nurses at two hospitals in Ghana. Awareness
      of cervical cancer was very high among the nurses. However, the majority of the
      participants held negative perceptions about cervical cancer and lacked knowledge
      about cervical cancer risk factors and prevention. The results can be used to
      inform the development of culturally-relevant cervical cancer education
      interventions targeted towards women and healthcare providers in LMICs.

PMID- 29334013
TI  - Understanding Teacher Change: A National Survey of U.S. Physical Educators.
AB  - : Physical education is critical to addressing childhood obesity, yet many school
      based programs do not meet established quality standards and teachers are called
      upon to change. Little is known about how change is initiated and its associated
      internal and external factors. PURPOSE: The purpose of this study was to
      investigate physical education teacher change that was self-initiated and
      externally initiated and to examine dispositions toward the change process
      relative to initiation. METHOD: A random national sample of physical educators
      representing each SHAPE America - Society of Health and Physical Educators
      regional district participated in a survey measuring past programming changes,
      primary initiators of change, and teachers' dispositions toward change. In total,
      2,423 teachers (46% response rate) completed electronic, paper, or telephone
      questionnaires. RESULTS: Teachers most often made minor curriculum changes, and
      they added/subtracted student assessments (primarily informal assessments) least
      often. Self-initiated (bottom-up) change was most frequently (83.1% of the time)
      reported. Externally initiated (top-down) changes were less frequent and were
      most often associated with professional development. Teachers reported
      principals' involvement in both top-down and bottom-up change processes was
      minimal. Teachers who were more disposed to making future changes reported making
      significantly (p < .01, eta2 = .046-.119) more past changes than those who were
      less disposed to change. CONCLUSIONS: Physical education teachers primarily self
      initiated minor programming changes without involvement from administration.
      Externally initiated change was infrequent and mostly involved professional
      development. Dispositions toward change were individual and enduring such that
      teachers who had made more past changes were more likely to also make future
      changes.

PMID- 29334014
TI  - Using Applied Theater in Primary, Secondary, and Tertiary Prevention of Intimate
      Partner Violence: A Systematic Review.
AB  - There is an immediate need to advance knowledge around the effective prevention
      of intimate partner violence (IPV), which is responsible for significant negative
      health and well-being outcomes for women around the world. Creative approaches
      are being explored internationally-this systematic review provides a timely
      synthesis of applied theater interventions addressing primary, secondary, and
      tertiary IPV prevention. Six hundred and ten articles were identified through a
      comprehensive search of five cross-disciplinary databases. Eleven studies
      discussed in 15 quantitative and qualitative peer-reviewed articles and one book
      chapter met the inclusion criteria and were included in the review. Articles were
      appraised using a standardized quality assessment tool and were analyzed within
      the context of IPV prevention. Of the reviewed studies, five were classified as
      primary prevention, four secondary, and two focused on tertiary prevention.
      Specific strategies used by each of the studies included healthy relationship
      training, rising awareness and community advocacy, service provider training,
      bystander training, and working with survivors. While the paucity and quality of
      current literature make it difficult to determine overall efficacy, this review
      points to the potential of applied theater as a useful prevention strategy,
      particularly when interactive, participatory methods are incorporated. Further,
      applied theater could be an effective tool for working in culturally diverse
      settings as well as with minority groups. Future applied theater program planning
      needs to include comprehensive evaluation. More rigorous investigation, involving
      mixed-method research approaches, is required to fully understand the potential
      of applied theater as a tool in the context of IPV prevention.

PMID- 29334015
TI  - Efficacy of hyperbaric oxygen therapy in bacterial biofilm eradication.
AB  - OBJECTIVE: Chronic wounds typically require several concurrent therapies, such as
      debridement, pressure offloading, and systemic and/or topical antibiotics. The
      aim of this study was to examine the efficacy of hyperbaric oxygen therapy (HBOT)
      towards reducing or eliminating bacterial biofilms in vitro and in vivo. METHOD:
      Efficacy was determined using in vitro grown biofilms subjected directly to HBOT
      for 30, 60 and 90 minutes, followed by cell viability determination using
      propidium monoazide-polymerase chain reaction (PMA-PCR). The efficacy of HBOT in
      vivo was studied by searching our chronic patient wound database and comparing
      time-to-healing between patients who did and did not receive HBOT as part of
      their treatment. RESULTS: In vitro data showed small but significant decreases in
      cell viability at the 30- and 90-minute time points in the HBOT group. The in
      vivo data showed reductions in bacterial load for patients who underwent HBOT,
      and ~1 week shorter treatment durations. Additionally, in patients' chronic
      wounds there was a considerable emergence of anaerobic bacteria and fungi between
      intermittent HBOT treatments. CONCLUSION: The data demonstrate that HBOT does
      possess a certain degree of biofilm killing capability. Moreover, as an adjuvant
      to standard treatment, more favourable patient outcomes are achieved through a
      quicker time-to-healing which reduces the chance of complications. Furthermore,
      the data provided insights into biofilm adaptations to challenges presented by
      this treatment strategy which should be kept in mind when treating chronic
      wounds. Further studies will be necessary to evaluate the benefits and mechanisms
      of HBOT, not only for patients with chronic wounds but other chronic infections
      caused by bacterial biofilms.

PMID- 29334016
TI  - Case report to demonstrate the need for selection criteria for optimal adjustable
      Velcro wrap prescription.
AB  - Compression, in the form of either a compression bandage or a compression
      stocking, has been touted as the gold standard for treatment of swelling and
      venous leg ulcers (VLUs). Adjustable Velcro wraps have been marketed as
      compression alternative. Although there is a growing body of evidence to support
      use of these products, there has not been a critical evaluation of the
      functionality of the devices to best matching product to patient presentation and
      ability to use the device effectively. Unlike compression garments, which are
      classified by compression category (class I/II or flat knit/circular), there is
      not an algorithm to direct health professionals to best match a specific
      adjustable Velcro wrap to an individual patient presentation. This small case
      series demonstrates that although each product performed as marketed in vitro,
      performance in clinical setting varied greatly dependent on patient presentation
      and functional skill level.

PMID- 29334017
TI  - Simplifying the simple: pressure-based tissue injuries for dummies.

PMID- 29334018
TI  - Pyoderma gangrenosum demographics, treatments, and outcomes: an analysis of 2,273
      cases.
AB  - OBJECTIVE: Pyoderma gangrenosum is a rare, neutrophil-mediated, auto-inflammatory
      dermatosis. This condition has clinical features analogous to infectious
      processes and must be quickly diagnosed to be properly treated. The purpose of
      this study was to characterise relevant clinical features associated with
      pyoderma gangrenosum based on a large inpatient cohort. METHOD: The National
      Inpatient Sample (US) was used to identify patients with the diagnosis of
      pyoderma gangrenosum using ICD-9 diagnosis code 686.01, during the years 2008
      2010. Data was collected on demographics, associated diagnoses, treatments and
      outcomes. Data analysis was performed using SAS 9.3 software. RESULTS: A total of
      2,273 adult patients were identified with pyoderma gangrenosum. Mean age was 56
      years; 66.4% were female; 71.1% were Caucasian. Pyoderma gangrenosum was the
      primary diagnosis in 22.6% of patients, followed by cellulitis (9.4%),
      inflammatory bowel disease (IBD) (6.9%), wound/ulcer (5.4%), sepsis (4.7%), and
      postoperative infection/complication (2.7%). The most common procedures performed
      were wound debridement (5.3%), skin biopsy (5.1%), esophagogastroduodenoscopy
      (2%), large bowel biopsy (1.9%), and incision and drainage (1.1%). A total of 74
      patients (3.2%) died during hospitalisation. CONCLUSION: Pyoderma gangrenosum is
      a serious skin condition, frequently associated with systemic disease, and often
      confused with other skin pathergies. Pyoderma gangrenosum should be considered
      when evaluating patients with ulcers, wounds, and post-operative complications. A
      high index of suspicion is necessary for early and accurate diagnosis and prompt
      treatment.

PMID- 29334019
TI  - Chemical stabilization of polymers: Implications for dermal exposure to
      additives.
AB  - Technical benefits of additives in polymers stand in marked contrast to their
      associated health risks. Here, a multi-analyte method based on gas chromatography
      coupled to tandem mass spectrometry (GC-MS/MS) was developed to quantify polymer
      additives in complex matrices such as low-density polyethylene (LDPE) and
      isolated human skin layers after dermal exposure ex vivo. That way both technical
      aspects and dermal exposure were investigated. The effects of polymer
      additivation on the material were studied using the example of LDPE. To this end,
      a tailor-made polymer was applied in aging studies that had been furnished with
      two different mixtures of phenol- and diarylamine-based antioxidants,
      plasticizers and processing aids. Upon accelerated thermo-oxidative aging of the
      material, the formation of LDPE degradation products was monitored with
      attenuated total reflectance-Fourier transformed infrared (ATR-FTIR)
      spectroscopy. Compared to pure LDPE, a protective effect of added antioxidants
      could be observed on the integrity of the polymer. Further, thermo-oxidative
      degradation of the additives and its kinetics were investigated using LDPE or
      squalane as matrix. The half-lives of additives in both matrices revealed
      significant differences between the tested additives as well as between LDPE and
      squalane. For instance, 2-tert-butyl-6-[(3-tert-butyl-2-hydroxy-5
      methylphenyl)methyl]-4-methylphenol (Antioxidant 2246) showed a half-life 12
      times lower when incorporated in LDPE as compared to squalane. As a model for
      dermal exposure of consumers, human skin was brought into contact with the tailor
      made LDPE containing additives ex vivo in static Franz diffusion cells. The skin
      was then analyzed for additives and decomposition products. This study proved 10
      polymer additives of diverse pysicochemical properties and functionalities to
      migrate out of the polymer and eventually overcome the intact human skin barrier
      during contact. Moreover, their individual distribution within distinct skin
      layers was demonstrated. This is exemplified by the penetration of the
      procarcinogenic antioxidant N-phenylnaphthalen-2-amine (Neozon D) into the viable
      epidermis and the permeation through the skin of the neurotoxic plasticizer N
      butylbenzenesulfonamide (NBBS). In addition, the analyses of additive degradation
      products in the isolated skin layers revealed the presence of 2-tert-butyl-4
      methylphenol in all layers after contact to a polymer with substances of origin
      like Antioxidant 2246. Thus, attention needs to be paid to absorption of polymer
      additives together with their degradation products when it comes to dermal
      exposure assessment.

PMID- 29334020
TI  - Gender-atypical personality or sexual behavior: What is disgusting about male
      homosexuality?
AB  - Research consistently finds that homosexuality elicits strong feelings of
      disgust, but the reasons remain unclear. In the current research, we investigate
      responses to gay men who violate social norms governing the expression of gender
      and sexuality. Two hundred forty-three college undergraduates read a vignette
      about a gay male college student whose personality traits (masculine, feminine,
      or neutral) and sexual behavior (active vs. passive) varied and reported their
      affective responses to and cognitive appraisals of the target. The gay target who
      displayed a feminine personality elicited more disgust and was perceived as lower
      in gender role conformity than a gay man who displayed a masculine personality.
      Similarly, the gay target who assumed a passive sex role elicited more disgust
      and was perceived as lower in gender role conformity than a gay man who assumed
      an active sex role. The sexual behavior/disgust relationship was mediated by
      perceived gender role conformity.

PMID- 29334021
TI  - A Comparison of Training and Competition Demands in Semiprofessional Male
      Basketball Players.
AB  - PURPOSE: The purpose of this study was to quantify and compare training and
      competition demands in basketball. METHODS: Fifteen semiprofessional male
      basketball players wore microsensors during physical conditioning training (PCT),
      games-based training (GBT), and competition to measure absolute and relative
      (.min-1) PlayerLoadTM (PL) and estimated equivalent distance (EED). Internal
      responses were calculated using absolute and relative session rating of perceived
      exertion (sRPE) and summated heart rate zones (SHRZ). Integrated measures were
      calculated as sRPE:PL and SHRZ:PL ratios. RESULTS: PlayerLoad (arbitrary units
      [AU]) and EED (m) were statistically significantly (p < .05) higher during PCT
      (632 +/- 139 AU, d = 1.36; 5,964 +/- 1,312 m, d = 1.36; 6.50 +/- 0.81 AU.min-1, d
      = 2.44; 61.88 +/- 7.22 m.min-1, d = 2.60) and GBT (624 +/- 113 AU, d = 1.54;
      5,892 +/- 1,080 m, d = 1.53; 6.10 +/- 0.77 AU.min-1, d = 2.14; 56.76 +/- 6.49
      m.min-1, d = 2.22) than they were during competition (449 +/- 118 AU; 3,722 +/-
      1474 m; 4.35 +/- 1.09 AU.min-1; 41.01 +/- 10.29 m.min-1). Summated heart rate
      zones were statistically significantly (p < .05) higher during PCT (314 +/- 86
      AU, d = 1.05; 3.22 +/- 0.50 AU.min-1, d = 1.94) and GBT (334 +/- 79 AU, d = 1.38;
      3.19 +/- 0.54 AU.min-1, d = 1.83) than they were during competition (225 +/- 77
      AU; 2.17 +/- 0.69 AU.min-1). The ratio of sRPE:PL was statistically significantly
      (p < .05) higher during competition (1.58 +/- 0.85) than during PCT (0.98 +/-
      0.22, d = 1.44) and GBT (0.91 +/- 0.24, d = 1.90). CONCLUSION: Training demands
      exceeded competition demands.

PMID- 29334022
TI  - Practitioners' Views on IPV and Its Solutions: An Integrative Literature Review.
AB  - There are ongoing debates in the scientific community and in practice settings
      about how intimate partner violence (IPV) should be defined and understood and
      about how various interventions must be carried out. If these debates are to bear
      fruit, however, we must first gain a comprehensive understanding of each
      stakeholder's viewpoints on IPV and its solutions. This article seeks to
      contribute to this goal by summarizing empirical studies investigating how
      practitioners who work with IPV perpetrators understand the problem and its
      solutions. Based on an integrative review of the literature, it focuses on how
      practitioners define IPV and its causes, how they perceive the perpetrators and
      victims, and on the solutions they put forward in order to work against this
      social problem. The limitations of our current knowledge are outlined as well as
      the implications of this review for IPV debates.

PMID- 29334023
TI  - Gender differences in inappropriate use of urinary catheters among hospitalized
      older patients.
AB  - This study investigated the incidence, rationales, and associated factors of
      inappropriate urinary catheter use among hospitalized older patients by gender. A
      longitudinal study of 321 patients with urinary catheter was conducted.
      Demographic factors, present health factors, urinary catheter factors, and
      indications of catheter use were collected. A total of 53.7% of urinary catheter
      days were inappropriate. For both men and women, there was no significant
      difference in the incidence and common rationales of inappropriate use. Women,
      however, have another associated factor with inappropriate use. More tailored
      alternatives are needed for women to increase comfort to avoid inappropriate
      catheter use.

PMID- 29334024
TI  - State of the Evidence: A Systematic Review of Approaches to Reduce Gender-Based
      Violence and Support the Empowerment of Adolescent Girls in Humanitarian
      Settings.
AB  - Adolescent girls are at an increased risk of sexual violence, abuse,
      exploitation, and forced or early marriage across humanitarian contexts. In the
      past few years, prominent initiatives, organizations, and working groups have
      started to highlight the targeted needs and issues facing adolescent girls and
      have developed programmatic responses such as safe spaces for adolescent girls to
      protect and empower girls and reduce their vulnerabilities to violence or
      exploitation. A systematic review of academic and grey literature was conducted
      in September 2015 to examine the evidence base for programming that seeks to
      reduce violence against adolescent girls in humanitarian contexts. The authors
      used a Boolean search procedure to find and review 5830 records from academic
      journal databases, resource-hosting websites and relevant organizational
      websites. The inclusion criteria left us with three adolescent girl program
      evaluations from humanitarian settings to examine, all of which were pre/post
      test evaluations that looked at changes in indicators such as social assets, self
      esteem, decision making, livelihood skills and financial assets, gender norms,
      and feelings of safety. While these three evaluations showed promising results,
      overall, this systematic review demonstrates a significant gap in currently
      available rigorous research. Evidence is urgently needed to guide programming
      decisions to ensure that the emerging programs provide the level and depth of
      protection that adolescent girls need in humanitarian settings.

PMID- 29334025
TI  - Heart Failure: The Increasing Need for a Focus on Self-Care.

PMID- 29334026
TI  - A guide to breast implants for the non-breast specialist.
AB  - Breast augmentation is an increasingly popular cosmetic surgery procedure, and
      breast implants can also be used in reconstructive surgery following mastectomy.
      Problematic breast implants can present to any discipline of medicine, most
      frequently to primary care or acute service such as emergency medicine. This
      guide aims to inform the non-breast specialist in how to assess and treat common
      problems and when referral to specialist services is necessary.

PMID- 29334029
TI  - The Relationship Between Childhood Maltreatment and Violence to Others in
      Individuals With Psychosis: A Systematic Review and Meta-Analysis.
AB  - BACKGROUND: There is a growing body of literature identifying a relationship
      between experiences of child abuse and symptoms of psychosis in adults. However,
      the impact of this relationship on risk of violence has not been systematically
      explored. AIMS: This meta-analysis aimed to consider the influence of childhood
      abuse on the risk of violence among individuals with psychosis. METHOD: Five
      bibliographic databases and two gray literature resources were systematically
      searched to identify quantitative research which measured risk of violence and
      experiences of childhood maltreatment in individuals with psychosis. Risk of bias
      for each study was assessed under predefined criteria. Logged odds ratios ( OR)
      were synthesized quantitatively in a meta-analysis. RESULTS: A total of 6,298
      studies were identified, 11 of which were included in the final analysis ( N =
      2,215), all studies were of a cross-sectional or case-control design. Individuals
      with psychotic illnesses who reported historical child maltreatment were at
      approximately twice the risk of perpetrating violence than patients who reported
      no early abuse, OR = 2.46, 95% confidence interval (CI) = [1.91, 3.16]. There was
      no statistical heterogeneity between main effects (tau = .00; chi2 = 8.87, df =
      10, p = .54, I2 = 0%). DISCUSSION: Risk assessments and interventions may benefit
      from considering the unique contribution of trauma to violence in this
      population. Future research considering the interaction between childhood
      experiences and other risk factors for violence in this population, including
      specific symptoms of psychosis, would inform the current findings. Findings are
      limited by the lack of longitudinal research in this area, and there was some
      evidence of publication bias.

PMID- 29334028
TI  - Differential diagnosis and management of placental polyp and uterine
      arteriovenous malformation: Case reports and review of the literature.
AB  - Postpartum uterine bleeding is not uncommon and is caused by a variety of
      obstetrical and gynecological disorders, such as retained placenta, dysfunctional
      bleeding, and endometrial polyps. Placental polyps and uterine arteriovenous
      malformation are disorders often encountered in cases of abnormal uterine
      bleeding in the late puerperal period. These patients may experience life
      threatening bleeding and require prompt intervention based on the correct
      differential diagnosis. The optimal treatments for both diseases differ as
      follows: intrauterine curettage or transcervical resection are chosen for
      placental polyps, while total abdominal hysterectomy or uterine artery
      embolization is preferred for uterine arteriovenous malformation since
      intrauterine curettage or transcervical resection has the risk of massive
      bleeding. However, since placental polyp and uterine arteriovenous malformation
      have similar clinical characteristics, it is important to accurately identify and
      differentiate between them to ensure optimal therapy. We report here cases that
      were suggestive of placental polyp or uterine arteriovenous malformation. We
      discuss the differential diagnoses and treatments for both diseases based on a
      literature review and propose a novel algorithm for managing such patients.

PMID- 29334027
TI  - Patient-Specific Quality Assurance Using Monte Carlo Dose Calculation and Elekta
      Log Files for Prostate Volumetric-Modulated Arc Therapy.
AB  - Log file-based methods are attracting increasing interest owing to their ability
      to validate volumetric-modulated arc therapy outputs with high resolution in the
      leaf and gantry positions and in delivered dose. Cross-validation of these
      methods for comparison with measurement-based methods using the ionization
      chamber/ArcCHECK-3DVH software (version 3.2.0) under the same conditions of
      treatment anatomy and plan enables an efficient evaluation of this method. In
      this study, with the purpose of cross-validation, we evaluate the accuracy of a
      log file-based method using Elekta log files and an X-ray voxel Monte Carlo dose
      calculation technique in the case of leaf misalignment during prostate volumetric
      modulated arc therapy. In this study, 10 prostate volumetric-modulated arc
      therapy plans were used. Systematic multileaf collimator leaf positional errors
      (+/-0.4 and +/-0.8 mm for each single bank) were deliberately introduced into the
      optimized plans. Then, the delivered 3-dimensional doses to a phantom with a
      certain patient anatomy were estimated by our system. These doses were compared
      with the ionization chamber dose and the ArcCHECK-3DVH dose. For the given
      phantom and patient anatomy, the estimated dose strongly coincided with the
      ionization chamber/ArcCHECK-3DVH dose ( P < .01). In addition, good agreement
      between the estimated dose and the ionization chamber/ArcCHECK-3DVH dose was
      observed. The dose estimation accuracy of our system, which combines Elekta log
      files and X-ray voxel Monte Carlo dose calculation, was evaluated.

PMID- 29334030
TI  - Commercial Sexual Exploitation of Youth in the United States: A Qualitative
      Systematic Review.
AB  - BACKGROUND: Homeless, runaway, and transgender youth are at high risk for
      commercial sexual exploitation in the United States. Research examining this
      phenomenon is growing but requires synthesis to facilitate its use by
      professionals who serve this population. The purpose of this review was to
      aggregate the qualitative evidence regarding commercially sexually exploited
      youth (CSEY) in the United States. METHODS: The search included published and
      unpublished qualitative studies with current or former CSEY who reside in the
      United States. RESULTS: There were 19 studies included in the review with a total
      of 795 participants. Eight themes were identified and grouped into three broader
      categories: experiences that preceded sex work entry, experiences that
      facilitated sex work continuation, and experiences that facilitated sex work
      exit. CONCLUSIONS: Understanding the barriers and facilitators of commercial
      sexual exploitation can inform the development of interventions that address the
      needs of CSEY and youth at risk for exploitation. The results of this review
      highlight the social and economic influences as well as the role of positive and
      negative reinforcements involved in sex work entry, its continuation, and exit.
      Needs for services, research, and advocacy are also discussed.

PMID- 29334031
TI  - A Profile of Gender-Based Violence Research in Europe: Findings From a Focused
      Mapping Review and Synthesis.
AB  - This article reports the findings from a new form of review: a focused mapping
      review and synthesis. The aim was to create a contemporary, snapshot profile of
      the nature and scope of gender-based violence (GBV) studies conducted in Europe.
      GBV is one of the most prevalent human rights violations in the world affecting
      mainly women and girls. The policy context of GBV in Europe has gathered momentum
      in recent years, but we do not have a clear picture of how this relates to
      research activity. Thirteen journals were purposively selected on their
      likelihood to publish GBV research. All articles published in these journals
      during 2015 and meeting our inclusion criteria were retrieved. Data were
      extracted according to (1) types of methodologies used, (2) geographical location
      of research, and (3) patterns of research activity/interest. Thirty-two articles
      met the inclusion criteria. Many titles and abstracts were not explicit about the
      gendered nature of the research which made retrieval and analysis difficult. A
      range of methodologies were reported, with single-country research conducted more
      than international collaborations. Intimate partner violence and sexual abuse
      attracted most research interest. No studies explored female genital
      mutilation/cutting and only one investigated early and forced marriage. The
      findings have implications regarding GBV research in Europe, and we explore them
      in relation to relevant European policy. Researchers can help raise the profile
      of the gendered nature of most violence-related research by being explicit about
      this in their publications. Increasing opportunities for cross-national research
      will help address the global nature of GBV. Tackling GBV requires synergy of
      empirical evidence and policy to drive the agenda.

PMID- 29334032
TI  - Obscure Dichotomy of Early Childhood Trauma in PTSD Versus Attachment Disorders.
AB  - There are two competing schools of thoughts involving children who have
      experienced early childhood trauma. One posture's nosology focuses on the post
      traumatic stress responses; the other focuses on the deviant behaviors that ensue
      from pathogenic care in early childhood. This author sought to review the
      literature from a holistic perspective, embracing both diagnostic positions.
      Seventy-three articles addressing childhood trauma and the ensuing emotional or
      behavioral disturbances were evaluated, mostly empirical-including 16 that
      specified posttraumatic stress disorder (PTSD), 21 that specified attachment
      disorders, and 37 that included potential overlaps between both trauma
      derivatives. An additional 138 studies were reviewed but not included herein
      because those focused on broader issues. Statistical data, financial and
      emotional impacts, and the effects of disrupted attachments were addressed
      including both children with secure attachments and those with compromised
      attachments. The critical effect of both positive and negative parental responses
      was evaluated, as well as correlations or overlaps in the diagnostic criteria and
      symptom manifestations of the children and any apparent gaps in the current
      research. The literature details that the prognosis and course of treatment vary
      significantly between the two etiologies-apparently at least in part due to
      possible clinician bias in conceptualizations of the two populations. There are
      clear overlaps in the diagnostic criteria that strongly suggest comorbidity
      between the disorders, however, which is especially critical to analyze in the
      future, since there are solid, empirical, evidence-based treatment protocols for
      PTSD, but not for attachment disorders resulting from pathogenic caregiver
      maltreatment.

PMID- 29334033
TI  - Reappraising and Redirecting Research on the Victim-Offender Overlap.
AB  - The strong positive association between offending and victimization, or the
      victim-offender overlap, has received considerable amount of research attention
      in recent years. Empirical research has made important strides in unpacking the
      sources of the phenomenon, but important questions remain unanswered. Ambiguity
      surrounds the utility of certain theoretical explanations for the overlap, the
      nature of the phenomenon, and the methodological tools used to examine its
      etiology. Owing to these knowledge gaps, the scientific meaning of the victim
      offender overlap is unclear. Moreover, a number of potentially important
      theoretical arguments are rarely subject to empirical testing in this line of
      research. The purpose of this article is to use a narrative review methodology to
      provide a critical reappraisal of the theoretical, empirical, and methodological
      research on the victim-offender overlap and offer directions for ways forward to
      develop a more comprehensive understanding of the phenomenon. This review
      includes critical analysis of 78 academic publications, along with a table that
      summarizes the key findings and conclusions from 18 critical empirical studies
      that have contributed to our understanding of the victim-offender overlap. We
      offer recommendations for the continued development of theoretical and
      methodological tools to better understand this complex phenomenon.

PMID- 29334034
TI  - Improved exogenous DNA uptake in bovine spermatozoa and gene expression in
      embryos using membrane destabilizing agents in ICSI-SMGT.
AB  - Sperm-mediated gene transfer (SMGT) is a simple, fast, and economical
      biotechnological tool for producing transgenic animals. However, transgene
      expression with this technique in bovine embryos is still inefficient due to low
      uptake and binding of exogenous DNA in spermatozoa. The present study evaluated
      the effects of sperm membrane destabilization on the binding capacity, location
      and quantity of bound exogenous DNA in cryopreserved bovine spermatozoa using
      Triton X-100 (TX-100), lysolecithin (LL) and sodium hydroxide (NaOH). Effects of
      these treatments were also evaluated by intracytoplasmic sperm injection (ICSI)
      SMGT. Results showed that all treatments bound exogenous DNA to spermatozoa
      including the control. Spermatozoa treated with different membrane destabilizing
      agents bound the exogenous DNA throughout the head and tail of spermatozoa,
      compared with the control, in which binding occurred mainly in the post-acrosomal
      region and tail. The amount of exogenous DNA bound to spermatozoa was much higher
      for the different sperm treatments than the control (P < 0.05), most likely due
      to the damage induced by these treatments to the plasma and acrosomal membranes.
      Exogenous gene expression in embryos was also improved by these treatments. These
      results demonstrated that sperm membrane destabilization could be a novel
      strategy in bovine SMGT protocols for the generation of transgenic embryos by
      ICSI.

PMID- 29334035
TI  - Neural correlates of ostracism in transgender persons living according to their
      gender identity: a potential risk marker for psychopathology?
AB  - BACKGROUND: Stigmatization in society carries a high risk for development of
      psychopathology. Transgender persons are at particularly high risk for such
      stigmatization and social rejection by others. However, the neural correlates of
      ostracism in this group have not been captured. METHOD: Twenty transgender men
      (TM, female-to-male) and 19 transgender women (TW, male-to-female) already living
      in their gender identity and 20 cisgender men (CM) and 20 cisgender women (CW)
      completed a cyberball task assessing both exclusion and re-inclusion during
      functional magnetic resonance imaging (fMRI). RESULTS: During psychosocial stress
      between-group differences were found in the dorsal and ventral anterior cingulate
      cortex (ACC) and the inferior frontal gyrus (IFG). Patterns were consistent with
      sex assigned at birth, i.e. CW showed greater activation in dorsal ACC and IFG
      relative to CM and TW. During re-inclusion, transgender persons showed greater
      ventral ACC activity relative to CW, possibly indicating persistent feelings of
      exclusion. Functional connectivity analyses supported these findings but showed a
      particularly altered functional connectivity between ACC and lateral prefrontal
      cortex in TM, which may suggest reduced emotional regulation to the ostracism
      experience in this group. Depressive symptoms or hormonal levels were not
      associated with these findings. CONCLUSION: The results bear implications for the
      role of social exclusion in development of mental health problems in socially
      marginalized groups.

PMID- 29334036
TI  - Short-term storage of the oocytes affects the ploidy status in the yellowtail
      tetra Astyanax altiparanae.
AB  - In fish, many factors can affect reproduction during in vitro fertilization,
      therefore determination of the factors that affect affecting gamete quality is
      needed. However, few studies have focused on gamete quality and the ploidy
      status. This study was conducted to elucidate whether oocyte storage can affect
      ploidy status, survival, and embryo viability in the characid species Astyanax
      altiparanae. Oocytes were stored in Dulbecco's phosphate-buffered saline (PBS) at
      26 degrees C, then aliquots were fertilized immediately after extrusion (control)
      and also after 60, 120, 180, and 240 min of storage. Fertilization and hatching
      rates were measured, and the developmental stages were analyzed at each stage
      before describing the main abnormalities. Ploidy status was analyzed by flow
      cytometry and blood smear. In the control group, 100% of the samples were
      diploid. After treatment for 60 min, 95.56 +/- 4.44% samples were diploid and
      4.44 +/- 4.44% were triploid. After 120 min, 94.44 +/- 9.62% of the samples was
      diploid and 5.56 +/- 5.56% were triploid; 100% of the samples were diploid after
      180 min and, after 240 min, there was no survival. In other treatments, the
      highest percentage of hatching was after 60 min (88.93 +/- 5.15%; P = 0.015), and
      treatment with 180 min storage resulted in the highest percentage of abnormal
      larvae (95.76 +/- 12.67%; P = 0.012). These results show that oocyte storage can
      affect ploidy status and may be an interesting parameter for analysis in studies
      on chromosome set manipulation and micromanipulation.

PMID- 29334037
TI  - Improvement in the Prognosis of Cerebral Venous Sinus Thrombosis over a 22-Year
      Period.
AB  - BACKGROUND: Cerebral venous thrombosis is a rare cause of stroke, with a number
      of well-defined risk factors. However, there exist few studies that describe
      trends in the prognosis of this disease over time. METHODS: A retrospective study
      was performed on patients diagnosed with cerebral venous thrombosis at the
      University of Alberta Hospital during two time periods: 1988-1998 (21 patients)
      and 1999-2009 (40 patients). Signs and symptoms, risk factors, imaging findings,
      etiologies, treatment modalities, and status at discharge were examined. RESULTS:
      Headache, nausea and vomiting, focal motor deficit, and seizure were the most
      common signs and symptoms, and active hormonal contraception was the most
      commonly identified risk factor between the two cohorts. Hematoma and hyperdense
      sinuses were the most commonly identified CT findings between groups.
      Thrombophilia and the use of hormonal contraception were the most frequently
      identified etiologies between the two cohorts. Treatment was similar, with the
      majority of patients in both cohorts receiving unfractionated heparin as first
      line therapy. Patients in the 1999-2009 cohort were significantly less likely to
      have a severe deficit or be dead at discharge (odds ratio [OR]=0.178; 95%
      confidence interval [CI 95%]=0.051, 0.625) and were more likely to have a
      favorable modified Rankin Scale score of 0 or 1 at discharge (OR=7.98; CI
      95%=1.79, 35.71). CONCLUSIONS: Our data indicate a reduction in severe residual
      symptoms at discharge and improved functional status at discharge for patients
      presenting with cerebral venous thrombosis from 1999 to 2009, as compared with
      1988-1998.

PMID- 29334038
TI  - Robotic-Assisted and Image-Guided MRI-Compatible Stereoelectroencephalography.
AB  - BACKGROUND: Stereoelectroencephalography has been in regular use at the Montreal
      Neurological Institute since 1972. The technique has been in constant evolution
      to incorporate advances in materials, imaging, and robotics technology. MRI
      compatible electrodes were introduced in 2007 and robotics in 2011. Here we
      report on the technique, safety, and advantages of our current method of
      stereoelectroencephalography implantation. METHODS: We retrospectively reviewed
      all patients who underwent stereoelectroencephalography by the senior author.
      Technical, clinical, and radiological complications, and postimplantation
      outcomes were analyzed. Only patients implanted with MRI-compatible electrodes
      were included to review MRI abnormalities with electrodes in situ. RESULTS: A
      total of 53 patients were implanted with 550 electrodes (average=10.4 per
      patient), for an average duration of 14.6 days. There was no mortality,
      infection, or new neurologic deficit. Two patients had a superficial screw plunge
      without clinical consequence. Four patients demonstrated asymptomatic MRI
      abnormalities (7.54% per patient, or 0.72% per electrode). MRI with electrodes in
      situ was used for neuronavigation in all 29 who underwent resection and yielded a
      histopathological diagnosis of focal cortical dysplasia in 15 MRI-negative
      patients. CONCLUSIONS: The technique of stereoelectroencephalography described
      here was associated with no clinical morbidity although not without technical
      complications or radiologic (MRI) abnormalities. We should therefore remain
      vigilant in refining the technique and minimizing the number of electrodes
      required to answer a well-developed hypothesis regarding the epileptogenic zone.
      The use of MRI-compatible electrodes allowed neuronavigation using the images
      with the electrodes in situ, which was useful to tailor the eventual definitive
      resection and in localizing MRI-negative lesions.

PMID- 29334039
TI  - Refractory Epilepsy: The Role of Positron Emission Tomography.
AB  - RATIONALE: Presurgical localization of the epileptogenic focus is critical to
      successful surgery. Traditionally, localization of the epileptogenic focus
      depends on seizure semiology, scalp video-electroencephalography (vEEG), magnetic
      resonance imaging (MRI), neuropsychological assessment, and, when needed,
      intracranial EEG (iEEG). We aimed to explore the role of positron emission
      tomography (PET) in the presurgical evaluation of patients with refractory
      epilepsy. METHODS: A retrospective review was conducted on patients from London
      Health Sciences Centre (London, Ontario) with refractory epilepsy who underwent
      PET from September of 2011 to April of 2016. The accuracy of epileptogenic focus
      localization was compared between different investigative modalities (MRI, vEEG,
      iEEG, PET), and the outcomes were documented, including seizure freedom after
      surgical resection, improvement of seizure frequency, guidance for further
      investigations, and exclusion of patients from further evaluation. Patients who
      underwent surgery were followed up at 3 months and onward. RESULTS: We identified
      62 patients with refractory epilepsy who underwent PET. The mean age was 34 years
      (range=20-68). A total of 36 had concordant PET and vEEG findings: 6 had surgical
      resection and either became seizure-free (29.4%) or had improvement in seizure
      frequency (5.9%) at 3 months; 11 had surgical resection and either became seizure
      free (29.4%) or had improvement in seizure frequency (35.3%) at 3 months, but
      required iEEG for final verification. CONCLUSIONS: PET has an important role in
      presurgical evaluation of patients with refractory epilepsy. It may allow
      resection of the epileptogenic focus without the need for iEEG, guiding
      intracranial electrode placement for further localization of the epileptogenic
      focus, or exclusion of patients from further evaluation.

PMID- 29334040
TI  - Botulinum Toxin Type A for Pain in Advanced Parkinson's Disease.
AB  - Background and Objective Pain is a frequent symptom in Parkinson's disease (PD),
      and the therapeutic alternatives are scarce. The goal of this trial was to
      measure the effects of botulinum toxin type A (BTXA) in the treatment of limb
      pain in advanced PD. Methods A randomized double-blind crossover versus placebo
      study of BTXA for limb pain in advanced Parkinson's disease was conducted.
      Subjects received individualized BTXA/placebo dosing per pain distribution in
      limbs. The primary outcome was a measure of change in global pain on a numeric
      rating scale (NRS) at 4 and 12 weeks postinjection and on a visual analogue scale
      12 weeks after treatment. Secondary outcomes included the percentage of
      responders, physician-rated clinical global impressions, MDS-UPDRS and PDQ-39
      scores, and adverse events. Results A total of 12 subjects completed the trial.
      Treatment with BTXA (average dose=241.66 U) produced a significant reduction in
      NRS score 4 weeks after the injections (-1.75 points, range from -3 to 7,
      p=0.033). However, there was no significant difference compared to placebo
      (p=0.70). Participants with dystonic pain showed a greater reduction in NRS score
      after 4 weeks when treated with BTXA (2.66 points vs. 0.75 for placebo). There
      were no significant differences for any of the secondary outcomes or significant
      adverse events. Conclusions Targeted BTXA injections were safe in patients with
      limb pain and advanced PD; however, the present study failed to show a
      significant effect when compared to placebo. Further studies may be focused on
      evaluating the effect of BTXA particularly in dystonic pain.

PMID- 29334041
TI  - Autoantibodies to Low-Density Lipoprotein Receptor-Related Protein 4 in Double
      Seronegative Myasthenia Gravis: A Systematic Review.
AB  - BACKGROUND: Myasthenia gravis (MG) is an autoimmune disorder of the neuromuscular
      junction in which a clinical diagnosis may be confirmed with serological testing.
      The most common autoantibodies used to support a diagnosis of MG are anti
      acetylcholine receptor antibodies and anti-muscle-specific tyrosine kinase
      antibodies. In cases in which both of these autoantibodies are negative (termed
      double-seronegative [dSNMG]), other autoantibodies such as low-density
      lipoprotein receptor-related protein 4 (LRP4) may be used to aid in diagnosis.
      METHODS: We have undertaken a systematic literature review to identify studies
      that have assessed the frequency of anti-LRP4 antibodies in dSNMG patients and
      the characteristics of anti-LRP4+ dSNMG patients (epidemiology, clinical
      features, electromyographic findings, or management). PubMed, EMBASE, Medline,
      and Scopus were searched on January 14, 2017, using the medical subject headings
      "myasthenia gravis" and "low-density lipoprotein receptor-related protein 4" or
      "LRP4." RESULTS: The initial search identified 367 articles. Fourteen
      publications met the inclusion criteria. There were ten cross-sectional research
      studies, three were case series, and one was a case report. The majority of
      studies were limited by small sample sizes of LRP4+ dSNMG. There has been a wide
      range of frequencies of anti-LRP4 antibodies detected in different MG patient
      populations, some involving different laboratory techniques. CONCLUSIONS: LRP4+
      dSNMG is more likely than LRP4- dSNMG to have a younger onset of disease and
      occur in females. LRP4+ dSNMG most often is mild in severity and often involves
      isolated ocular weakness. It typically responds well to pyridostigmine or
      prednisone.

PMID- 29334042
TI  - Orbital Myositis: An Underrecognized Clinical Syndrome with a Need of Management
      Guidelines.

PMID- 29334043
TI  - A Tribute to James Parkinson.
AB  - Exactly 200 years ago, the London surgeon-apothecary James Parkinson (1755-1824)
      published a 66-page-long booklet entitled An Essay on the Shaking Palsy, which
      contains the first clear clinical description of the shaking palsy or paralysis
      agitans, which we now refer to as Parkinson's disease. However, the value of this
      essay was not fully recognized during Parkinson's lifetime, which spanned the
      American Revolution, the French Revolution, and the Napoleonic Wars. James
      Parkinson was one of the most singular figures of his time and place. He was
      successively or concomitantly a virulent political activist, a popular medical
      writer, a scholarly medical contributor, a highly appreciated parish doctor, a
      prominent amateur chemist, a devoted madhouse doctor, and a renowned
      paleontologist. It is that branch of geology that brought Parkinson fame during
      his lifetime. He was an insatiable collector of fossils, minerals, and shells
      that came to form the core of the museum that he set out at his home in
      Shoreditch, England. These specimens are beautifully illustrated in his Organic
      Remains of a Former World (1804-1811), a three-volume treatise that rapidly
      became a standard paleontology textbook. Parkinson was a founding member of the
      Geological Society of London, and in recognition of his contribution to the
      nascent field of paleontology his name was given to many fossils, particularly
      ammonites (e.g. Nautilus parkinsoni). Hence, we owe much to Mr. Parkinson, the
      Paleontologist, as he used to be referred to after his death, for such a vast and
      multifaceted contribution to natural science and medicine.

PMID- 29334044
TI  - Gene-environment interplay in the etiology of psychosis.
AB  - Schizophrenia and other types of psychosis incur suffering, high health care
      costs and loss of human potential, due to the combination of early onset and poor
      response to treatment. Our ability to prevent or cure psychosis depends on
      knowledge of causal mechanisms. Molecular genetic studies show that thousands of
      common and rare variants contribute to the genetic risk for psychosis.
      Epidemiological studies have identified many environmental factors associated
      with increased risk of psychosis. However, no single genetic or environmental
      factor is sufficient to cause psychosis on its own. The risk of developing
      psychosis increases with the accumulation of many genetic risk variants and
      exposures to multiple adverse environmental factors. Additionally, the impact of
      environmental exposures likely depends on genetic factors, through gene
      environment interactions. Only a few specific gene-environment combinations that
      lead to increased risk of psychosis have been identified to date. An example of
      replicable gene-environment interaction is a common polymorphism in the AKT1 gene
      that makes its carriers sensitive to developing psychosis with regular cannabis
      use. A synthesis of results from twin studies, molecular genetics, and
      epidemiological research outlines the many genetic and environmental factors
      contributing to psychosis. The interplay between these factors needs to be
      considered to draw a complete picture of etiology. To reach a more complete
      explanation of psychosis that can inform preventive strategies, future research
      should focus on longitudinal assessments of multiple environmental exposures
      within large, genotyped cohorts beginning early in life.

PMID- 29334045
TI  - Development of a patient experience questionnaire to improve lifestyle services
      in primary care.
AB  - : Aim We developed a self-report tool to assess patients' experiences with
      lifestyle services in team-based primary care and pilot tested the questionnaire
      as part of a lifestyle intervention study to reverse metabolic syndrome.
      BACKGROUND: Older client satisfaction questionnaires have been generally
      inadequate for quality improvement purposes, as they have been focused mainly on
      interpersonal skills of providers and/or in the context of one disease. New
      approaches to assessing the patient experience of lifestyle programs in primary
      care are needed and could inform quality improvement efforts over time. METHODS:
      The first phase in developing the questionnaire involved a group-administered
      questionnaire distributed to 38 healthcare providers in five groups to prioritize
      variables to include in the survey. Concepts were taken from a previous review of
      available questionnaires assessing primary care services. The draft questionnaire
      was reviewed by 11 participants from a lifestyle program using think-aloud
      cognitive interviewing techniques. The modified self-administered questionnaire
      (paper and online versions) was then pilot tested with 164 recipients of a
      nutrition and physical activity intervention program. Findings Providers ranked
      the top variables to include in the questionnaire as: 'trust,' 'general
      communication,' 'first-contact accessibility,' 'whole-person care,' and
      'respectfulness.' After cognitive interviewing and revisions, 21 multiple choice
      and two open-ended questions were used for pilot testing. Pilot testing
      identified additional minor wording changes that were needed for clarity, a
      decreased number of questions for redundant concepts, and decreased options for
      ceiling effects, resulting in 20 multiple choice and one open-ended question.
      CONCLUSIONS: The modified self-administered patient experience questionnaire to
      assess lifestyle services in primary care has undergone rigorous development.
      Further validation is needed. The assessment of patient experience of lifestyle
      programs can be used to supplement other data to assess the overall effectiveness
      of such programs.

PMID- 29334046
TI  - Antimicrobial Activities of Novel Bis-Piperidinium Compounds.
AB  - The antimicrobial activity of two new series of bis-piperidinium compounds with
      alkyl chains of different lengths against bacterial (Escherichia coli,
      Pseudomonas aeruginosa, Staphylococcus aureus and Bacillus subtilis) and fungal
      strains (Aspergillus flavus, Aspergillus niger, Rhodolorula rubera, Lipomyces
      lopofera and Candida albicans), are described. Antimicrobial activities of the
      synthesized compounds were compared to that of dodecyltrimethylammonium chloride.
      Bis-piperidinium salts possessing 12-16 carbon side chains showed better
      antimicrobial properties as compared to the standard dodecyltrimethylammonium
      chloride.

PMID- 29334047
TI  - Partial Characterization of Bacteriocin Produced by Halotolerant Pediococcus
      acidilactici Strain QC38 Isolated from Traditional Cotija Cheese.
AB  - During a screening of lactic acid bacteria producing bacteriocin from Cotija
      cheese, the strain QC38 was isolated. Based on the 16S rRNA gene nucleotide
      sequencing (516 pb accession no KJ210322) and phylogenetic analysis, the isolate
      was identified as Pediococcus acidilactici. Neutralized cell-free supernatant was
      tested for antimicrobial activity against 17 Gram-negative and Gram-positive
      pathogens. Growth inhibition was achieved against Listeria monocytogenes
      (supplier or indication or source), Staphylococcus aureus, Vibrio vulnificus,
      Vibrio cholerae O1 Ogawa, Vibrio cholerae NO 01 and Salmonella enterica subsp.
      Enterica serovar Typhimurium. Bacteriocin-like substance, after heating at 121
      degrees C for 15 min it remained stable and its antimicrobial activity was
      observed at pH ranging from 1.0 to 10.0 but inactivated by alpha-chymotrypsin and
      proteinase K. Strain QC38 was able to grow in 1-9% NaCl concentration. The plate
      overlay assay showed an approximate size of bacteriocin-like substance between
      3.4 and 6.5 kDa. P. acidilactici QC38 harboured a plasmid that contains a gene
      for a pediocin (PA-1).

PMID- 29334048
TI  - Use of the Real Time xCelligence System for Purposes of Medical Microbiology.
AB  - Roche's xCelligence impedance-measuring instrument is one of a few commercially
      available systems of such type. According to the best knowledge of authors,
      instrument was tested so far only for eukaryotic cell research. The aim of this
      work was to estimate xCELLigence suitability for the microbiological tests,
      including (i) measurement of morphological changes in eukaryotic cells as a
      result of bacterial toxin activity, (ii) measurement of bacterial biofilm
      formation and (iii) impact of antiseptics on the biofilm structure. To test the
      infuence of bacterial LT enterotoxin on eukaryotic cell lines, Chinese Hamster
      Ovary (CHO) cell line and reference strain Escherichia coli ATTC 35401 were used.
      To investigate Roche's instrument ability to measure biofilm formation and impact
      of antiseptics on its development, Staphylococcus aureus ATTC6538 reference
      strain was used. The data generated during the experiments indicate excellent
      ability of xCelligence instrument to detect cytopathic effect caused by bacterial
      LT endotoxin and to detect staphylococcal biofilm formation. However,
      interpretation of the results obtained during real-time measurement of
      antiseptic's bactericidal activity against staphylococcal biofilm, caused many
      difficulties. xCelligence instrument can be used for real-time monitoring of
      morphological changes in CHO cells treated with bacterial LT enterotoxin and for
      real-time measurement of staphylococcal biofilm formation in vitro. Further
      investigation is necessary to confirm suitability of system to analyze
      antiseptic's antimicrobial activity against biofilm in vitro.

PMID- 29334049
TI  - Phylogenetic Analysis Based on 16S rRNA Gene of a Thermophilic Protease-Secreting
      Bacillus gelatini-TPNK-3 Isolate from Kiteezi Landfill, Uganda.
AB  - A thermophilic protease-secreting bacterial isolate, TPNK-3, from Kiteezi
      landfill, is an aerobic Gram-positive spore-forming bacterium with rod-shaped
      cells (3.28 MUm long and 0.45 MUm wide). Optimal growth was observed at 55
      degrees C and pH of 7.0, and the isolate tolerates up to 5% (w/v) NaCl, exhibits
      extracellular amylolytic, cellulolytic and caseinolytic activities, utilizes a
      range of carbon and nitrogen sources and has a GC content of 45 mol%. The 16S
      rRNA gene sequence analysis showed that the studied bacterium belongs to the
      genus Bacillus, and closest to Bacillus gelatini (>99.9%). Consequently, isolate
      TPNK3 is tentatively described as Bacillus gelatini strain TPNK3.

PMID- 29334050
TI  - Enzymatic Activity of Prototheca zopfii Strains Isolated from Cows with Mastitis.
AB  - Bovine mastitis caused by Prototheca spp. can be a disease of high significance
      because of economic losses and the potential risk to public health. The aim of
      our study was to evaluate enzymatic activity of Prototheca zopfii. For this
      study, we used 15 P. zopfii strains previously isolated from cows with clinical
      and subclinical mastitis in Poland. We determined enzymatic profile of Prototheca
      species using the API ZYM system. Of the enzymatic activities detected during the
      study, acid phosphatase, leucine arylamidase, naphthol-as-bi-phosphohydrolase,
      esterase, lipase esterase, valine arylamidase, alkaline phosphatase, and lipase
      C14 were found in high percentage of strains.

PMID- 29334051
TI  - Characterization of a Highly Enriched Microbial Consortium Reductively
      Dechlorinating 2,3-Dichlorophenol and 2,4,6-Trichlorophenol and the Corresponding
      cprA Genes from River Sediment.
AB  - Anaerobic reductive dechlorination of 2,3-dichlorophenol (2,3DCP) and 2,4,6
      trichlorophenol (2,4,6TCP) was investigated in microcosms from River Nile
      sediment. A stable sediment-free anaerobic microbial consortium reductively
      dechlorinating 2,3DCP and 2,4,6TCP was established. Defined sediment-free
      cultures showing stable dechlorination were restricted to ortho chlorine when
      enriched with hydrogen as the electron donor, acetate as the carbon source, and
      either 2,3-DCP or 2,4,6-TCP as electron acceptors. When acetate, formate, or
      pyruvate were used as electron donors, dechlorination activity was lost. Only
      lactate can replace dihydrogen as an electron donor. However, the dechlorination
      potential was decreased after successive transfers. To reveal chlororespiring
      species, the microbial community structure of chlorophenol-reductive
      dechlorinating enrichment cultures was analyzed by PCR-denaturing gradient gel
      electrophoresis (DGGE) of 16S rRNA gene fragments. Eight dominant bacteria were
      detected in the dechlorinating microcosms including members of the genera
      Citrobacter, Geobacter, Pseudomonas, Desulfitobacterium, Desulfovibrio and
      Clostridium. Highly enriched dechlorinating cultures were dominated by four
      bacterial species belonging to the genera Pseudomonas, Desulfitobacterium, and
      Clostridium. Desulfitobacterium represented the major fraction in DGGE profiles
      indicating its importance in dechlorination activity, which was further confirmed
      by its absence resulting in complete loss of dechlorination. Reductive
      dechlorination was confirmed by the stoichiometric dechlorination of 2,3DCP and
      2,4,6TCP to metabolites with less chloride groups and by the detection of
      chlorophenol RD cprA gene fragments in dechlorinating cultures. PCR amplified
      cprA gene fragments were cloned and sequenced and found to cluster with the
      cprA/pceA type genes of Dehalobacter restrictus.

PMID- 29334052
TI  - The Effect of a Small Conotoxin-Like ctx Gene from Autographa californica Nuclear
      Polyhedrosis Virus (AcMNPV) on Insect Hemolymph Melanization.
AB  - The conotoxin-like (ctx) gene encodes a small cysteine-rich polypeptide in
      various baculoviruses. Previous research has demonstrated that the product of the
      ctx gene could be purified from insect cells infected by Autographa californica
      nuclear polyhedrosis virus (AcMNPV), but its function was unknown. In this paper,
      we compared the conserved cysteine motif structure (CX3GX2CX5CCX3CX6C) of the ctx
      gene in baculoviruses and generated recombinant Bombyx mori nuclear polyhedrosis
      virus (BmNPV) with the BmNPV bacmid system. The recombinant BmNPV contained the
      ctx gene from AcMNPV or a fusion gene of ctx with eGFP, respectively.
      Fluorescence in CTX-eGFP-positive cells was mainly observed on the cell membrane.
      To gain insight into CTX function, two methods were used to elucidate the affect
      CTX had on hemolymph melanization in vivo and in vitro in insect larvae and
      pupae. The results indicated that CTX abrogates hemolymph melanization; however,
      the mechanisms require further evaluation.

PMID- 29334053
TI  - Complex Biochemical Analysis of Fruiting Bodies from Newly Isolated Polish
      Flammulina velutipes Strains.
AB  - The present study examined Polish strains of Flamulina velutipes as a potential
      source of nutraceuticals and found that their nutritional value is dependent on
      the fruiting bodies gathering time. To prove the above hypothesis protein,
      carbohydrate and phenolic substances concentration were determined. Moreover,
      catalase, superoxide dismutase, cellobiose dehydrogenase activities were assayed.
      In order to prove the healing properties of Enoki fruiting bodies the obtained
      extracts were tested for antioxidant and bacteriostatic abilities. We have proved
      that Polish F. velutipes fruiting bodies may be a rich source of antioxidants and
      that they are capable of inhibiting Staphylococcus aureus growth.

PMID- 29334054
TI  - Candida albicans Denture Biofilm and its Clinical Significance.
AB  - Fungi belonging to Candida genus, especially C. albicans play an important role
      in microflora of oral cavity. Microbial colonisation process taking place within
      oral cavity is inseparably related to formation of multispecies biofilm, i.e.
      dental and denture plaque. A mature fungal biofilm is a heterogeneous three
      dimensional dense conglomeration of mixture of different morphological forms:
      blastospores, germ tubes, pseudohyphae and hyphae surrounded by the extracellular
      polymeric matrix. Composition and specific properties of substratum, saliva and
      yeasts as well as multiple intricate interactions between all of them influence
      the ability of Candida spp. isolates to adhere and colonise both natural and
      artificial surfaces, followed by biofilm formation. Obviously, specific complex
      host-pathogen interactions also should not be neglected. A lot of additional
      factors like poor oral and denture hygiene, low pH under prosthesis, sufficient
      concentration of sugar and iron or antibody titres influence Candida adhesion and
      colonisation of acrylic resin base. C. albicans is capable of inducing a variety
      of superficial diseases of the oral mucosa. The most common clinical form of oral
      candidal infection related to biofilm formation affecting a great deal of denture
      wearers is denture-associated stomatitis, also known as chronic atrophic
      candidiasis or erythemateous candidasis. Development of C. albicans biofilm on a
      denture surface constitutes a difficult and hard to resolve problem which may
      concern every single prosthesis-wearer. Thus, careful oral and denture hygiene is
      highly recommended for the population of artificial teeth wearers.

PMID- 29334055
TI  - Endophytic Detection in Selected European Herbal Plants.
AB  - A total of 181 cultivable endophytic bacterial isolates were collected from stems
      of 13 species of herbs inhabiting Europe (Poland): Chelidonium majus L., Elymus
      repens L., Erigeron annuus L., Euphrasia rostkoviana Hayne, Foeniculum vulgare
      L., Geranium pratense L., Humulus lupulus L., Matricaria chamomilla L., Mentha
      arvensis L., Papaver rhoeas L., Rosmarinus officinalis L., Solidago gigantea L.
      and Vinca minor L. The isolates were screened for their antifungal activity and
      fifty three were found to inhibit fungal growth. Of these, five had strong
      antifungal properties. These selected isolates were identified as: Pseudomonas
      azotoformans, P. cedrina, Bacillus subtilis group and Erwinia persicina.

PMID- 29334056
TI  - Concept for Development of Expert Computer Program for Identification of
      Filamentous Fungi.
AB  - An expert program has been developed for users working in industrial laboratories
      who are not experts in the identification of filamentous fungi. The database of
      morphological growth features currently contains 12 species from the genera
      Aspergillus and Penicillium grown under standard conditions. The identification
      algorithm implemented in the database takes into account the reliability of
      users, which can vary over a wide range depending on the identification feature.
      The reliability of users was estimated on the basis of a questionnaire survey
      conducted among 27 non-experts, as the likelihood of a response consistent with
      the assessment of experts. The program works through comparative analysis of
      features of the fungus being identified with the expert-developed database and
      selection of the most likely species among the species represented by reference
      strains. The expert program reduces subjective mistakes and may be extended to
      include further fungal species and genera; it can also be supplemented with
      chemotaxonomic, genetic and other data.

PMID- 29334057
TI  - Characterization of Rhizobial Bacteria Nodulating Astragalus corrugatus and
      Hippocrepis areolata in Tunisian Arid Soils.
AB  - Fifty seven bacterial isolates from root nodules of two spontaneous legumes
      (Astragalus corrugatus and Hippocrepis areolata) growing in the arid areas of
      Tunisia were characterized by phenotypic features, 16S rDNA PCR-RFLP and 16S rRNA
      gene sequencing. Phenotypically, our results indicate that A. corrugatus and H.
      areolata isolates showed heterogenic responses to the different phenotypic
      features. All isolates were acid producers, fast growers and all of them used
      different compounds as sole carbon and nitrogen source. The majority of isolate
      grew at pHs between 6 and 9, at temperatures up to 40 degrees C and tolerated 3%
      NaCl concentrations. Phylogenetically, the new isolates were affiliated to four
      genera Sinorhizobium, Rhizobium, Mesorhizobium and Agrobacterium. About 73% of
      the isolates were species within the genera Sinorhizobium and Rhizobium. The
      isolates which failed to nodulate their host plants of origin were associated to
      Agrobacterium genus (three isolates).

PMID- 29334058
TI  - Prevalence of Biofilm Formation and Wide Distribution of Virulence Associated
      Genes among Vibrio spp. Strains Isolated from the Monastir Lagoon, Tunisia.
AB  - In the current study, 65 Vibrio spp. were isolated from the Monastir lagoon
      water, were characterized phenotypically and genotypically. In addition, we
      looked for the presence of three Vibrio parahaemolyticus virulence genes (tlh,
      trh and tdh) and ten Vibrio cholerae virulence genes (ctxA, vpi, zot, ace, toxR,
      toxT, tosS, toxRS, tcpA and cpP). We also investigated the antibiotic
      susceptibilities and the adherence ability of the identified strains to abiotic
      material and to biotic surfaces. The cytotoxicity activity against HeLa and Vero
      cell lines were also carried out for all tested strains. All Vibrio isolates were
      identified to the species level and produced several hydrolytic exoenzymes. The
      results also revealed that all strains were expressing high rates of resistance
      to tested antibiotics. The minimum inhibitory concentration (MIC) values showed
      that tetracycline and chloramphenicol were the most effective antibiotics against
      the tested bacteria. Vibrio alginolyticus and V. cholerae species were the most
      adhesive strains to both biotic and abiotic surfaces. Besides, V. alginolyticus
      isolates has the high levels of recombination of genes encoding V. cholerae and
      V. parahaemolyticus virulence factors. In vitro cytotoxic activities of several
      Vibrio extracellular product were also observed among HeLa and Vero cells.

PMID- 29334059
TI  - Molecular Characterization of Shiga Toxin-Producing Escherichia coli Strains
      Isolated in Poland.
AB  - Shiga toxin-producing Escherichia coli (STEC) strains also called verotoxin
      producing E. coli (VTEC) represent one of the most important groups of food-borne
      pathogens that can cause several human diseases such as hemorrhagic colitis (HC)
      and hemolytic - uremic syndrome (HUS) worldwide. The ability of STEC strains to
      cause disease is associated with the presence of wide range of identified and
      putative virulence factors including those encoding Shiga toxin. In this study,
      we examined the distribution of various virulence determinants among STEC strains
      isolated in Poland from different sources. A total of 71 Shiga toxin-producing E.
      coli strains isolated from human, cattle and food over the years 1996-2010 were
      characterized by microarray and PCR detection of virulence genes. As stx1a
      subtype was present in all of the tested Shiga toxin 1 producing E. coli strains,
      a greater diversity of subtypes was found in the gene stx2, which occurred in
      five subtypes: stx2a, stx2b, stx2c, stx2d, stx2g. Among STEC O157 strains we
      observed conserved core set of 14 virulence factors, stable in bacteria genome at
      long intervals of time. There was one cattle STEC isolate which possessed
      verotoxin gene as well as sta1 gene encoded heat-stable enterotoxin STIa
      characteristic for enterotoxigenic E. coli. To the best of our knowledge, this is
      the first comprehensive analysis of virulence gene profiles identified in STEC
      strains isolated from human, cattle and food in Poland. The results obtained
      using microarrays technology confirmed high effectiveness of this method in
      determining STEC virulotypes which provides data suitable for molecular risk
      assessment of the potential virulence of this bacteria. virulence factors
      including those encoding Shiga toxin. In this study, we examined the distribution
      of various virulence determinants among STEC strains isolated in Poland from
      different sources. A total of 71 Shiga toxin-producing E. coli strains isolated
      from human, cattle and food over the years 1996-2010 were characterized by
      microarray and PCR detection of virulence genes. As stx1a subtype was present in
      all of the tested Shiga toxin 1 producing E. coli strains, a greater diversity of
      subtypes was found in the gene stx2, which occurred in five subtypes: stx2a,
      stx2b, stx2c, stx2d, stx2g. Among STEC O157 strains we observed conserved core
      set of 14 virulence factors, stable in bacteria genome at long intervals of time.
      There was one cattle STEC isolate which possessed verotoxin gene as well as sta1
      gene encoded heat-stable enterotoxin STIa characteristic for enterotoxigenic E.
      coli. To the best of our knowledge, this is the first comprehensive analysis of
      virulence gene profiles identified in STEC strains isolated from human, cattle
      and food in Poland. The results obtained using microarrays technology confirmed
      high effectiveness of this method in determining STEC virulotypes which provides
      data suitable for molecular risk assessment of the potential virulence of this
      bacteria.

PMID- 29334060
TI  - Nonspecific Bacterial Flora Isolated from the Body Surface and Inside Ixodes
      ricinus Ticks.
AB  - Ixodes ricinus and other representatives of the order Ixodida are vectors of
      typical pathogens: Borrelia burgdorferi sensu lato, Anaplasma phagocytophilium,
      Babesia spp., a tick-borne encephalitis virus, and other microorganisms which are
      important from a medical and veterinary point of view. The presented study
      focuses on the verification of nonspecific bacterial flora of I. ricinus. We
      analyzed ticks collected in a forest region in Silesia, an industrial district in
      Poland. Methods of classical microbiology and biochemical assays (API 20 NE test,
      API Staph test and MICRONAUT System) were used for isolation and identification
      of microorganisms living on the body surface of I. ricinus and inside ticks. The
      results show the presence of various bacteria on the surface and inside ticks'
      bodies. During the study, we isolated Acinetobacter lwoffi, Pseudomonas
      fluorescens, Aeromonas hydrophila, Achromobacter denitrificans, Alcaligenes
      faecalis, Stenotrophomonas maltophilia, Pseudomonas oryzihabitans, Micrococcus
      spp., Kocuria varians, Staphylococcus lentus, Kocuria kristinae, Streptococcus
      pneumoniae, Rhizobium radiobacter, Staphylococcus xylosus. Majority of the
      isolated species are non-pathogenic environmental microorganisms, but some of the
      isolated bacterial strains could cause severe infections.

PMID- 29334061
TI  - The Effect of Local Platelet Rich Plasma Therapy on the Composition of Bacterial
      Flora in Chronic Venous Leg Ulcer.
AB  - Microbial colonisation of chronic venous ulcers and synergism between bacterial
      species slow down the healing process. The study aimed at performing qualitative
      analysis of microbial flora in venous leg ulcers treated with platelet rich
      plasma (PRP). Twenty two women and twelve men aged 47-90 years were treated with
      PRP at our department between 2012 and 2015. Ulcer cultures collected before and
      after PRP therapy yielded 83 and 110 microbial isolates, respectively, of Gram
      positive, Gram negative bacteria and candida. Pseudomonas aueruginosa and
      Staphylococcus aureus were the most common pre- and post-treatment isolates. PRP
      therapy and increased the variety of microbial flora.

PMID- 29334062
TI  - The Role of Staphylococcus aureus in Secondary Infections in Patients with Atopic
      Dermatitis (AD).
AB  - Staphylococcus aureus colonizes the mucous membrane of the nasal vestibule of a
      significant number of healthy people. These microorganisms are opportunistic
      pathogens, that in favorable conditions, may cause infections of various course,
      location or manifestation. Secondary infections emerge in cases when other risk
      factors contribute to such a change. One of the diseases during which S. aureus
      changes its saprophytic character to a pathogenic one is atopic dermatitis (AD),
      an allergic skin condition of a chronic and recurrent nature. Patients with AD
      are highly predisposed to secondary staphylococcal infections due to active S.
      aureus colonization of the stratum corneum, damage of the skin barrier or a
      defective immune response. Microorganisms present in skin lesions destroy the
      tissue by secreting enzymes and toxins, and additionally stimulate secondary
      allergic reactions. The toxins secreted by strains of S. aureus also act as
      superantigens and penetrate the skin barrier contributing to a chronic
      inflammation of the atopic skin lesions. The S. aureus species also releases
      proinflammatory proteins, including enzymes that cause tissue damage. When
      initiating treatment it is particularly important to properly assess that the
      onset of the secondary bacterial infection is caused by S. aureus and thus
      justifying the inclusion of antibiotic therapy. Depending on the severity and
      extent of the staphylococcal infection, topical antibiotics are used, usually
      mupirocin or fusidic acid, or general antibiotic treatment is introduced. Another
      therapeutic strategy without antibiotics has given a positive effect in patients.

PMID- 29334063
TI  - Penicillin Resistance in Enterococcus faecalis: Molecular Determinants and
      Epidemiology.
AB  - Enterococcus faecalis plays a significant role in hospital-acquired infections
      (HAIs), and combination of penicillin with aminoglycoside is important in therapy
      of invasive HAIs. Penicillin resistance in this organism is due to modification
      of the drug target, penicillin-binding protein (PBP5), its overproduction and
      expression of beta-lactamase. Although rare, this phenotype is often associated
      with multi-resistant high-risk enterococcal clonal complexes (HiRECCs), such as
      CC2 and CC9 which may promote its spread in the near future.

PMID- 29334064
TI  - Distribution and Identification of Endophytic Streptomyces Species from Schima
      wallichii as Potential Biocontrol Agents against Fungal Plant Pathogens.
AB  - The prospective of endophytic microorganisms allied with medicinal plants is
      disproportionally large compared to those in other biomes. The use of
      antagonistic microorganisms to control devastating fungal pathogens is an
      attractive and eco-friendly substitute for chemical pesticides. Many species of
      actinomycetes, especially the genus Streptomyces, are well known as biocontrol
      agents. We investigated the culturable community composition and biological
      control ability of endophytic Streptomyces sp. associated with an ethanobotanical
      plant Schima wallichi. A total of 22 actinobacterial strains were isolated from
      different organs of selected medicinal plants and screened for their biocontrol
      ability against seven fungal phytopathogens. Seven isolates showed significant
      inhibition activity against most of the selected pathogens. Their identification
      based on 16S rRNA gene sequence analysis, strongly indicated that all strains
      belonged to the genus Streptomyces. An endophytic strain BPSAC70 isolated from
      root tissues showed highest percentage of inhibition (98.3 %) against Fusarium
      culmorum with significant activity against other tested fungal pathogens.
      Phylogenetic analysis based on 16S rRNA gene sequences revealed that all seven
      strains shared 100 % similarity with the genus Streptomyces. In addition, the
      isolates were subjected to the amplification of antimicrobial genes encoding
      polyketide synthase type I (PKS-I) and nonribosomal peptide synthetase (NRPS) and
      found to be present in most of the potent strains. Our results identified some
      potential endophytic Streptomyces species having antagonistic activity against
      multiple fungal phytopathogens that could be used as an effective biocontrol
      agent against pathogenic fungi.

PMID- 29334065
TI  - Pexophagy in Penicillin G Secretion by Penicillium chrysogenum PQ-96.
AB  - Penicillin G oversecretion by Penicillium chrysogenum PQ-96 is associated with a
      strictly adjusted cellular organization of the mature and senescent mycelial
      cells. Abundant vacuolar phagy and extended cellular vacuolization combined with
      vacuolar budding resulting in the formation of vacuolar vesicles that fuse with
      the cell membrane are the most important characteristic features of those cells.
      We suggest as follows: if the peroxisomes are integrated into vacuoles, the
      penicillin G formed in peroxisomes might be transferred to vacuoles and later
      secreted out of the cells by an exocytosis process. The peroxisomal cells of the
      mycelium are privileged in penicillin G secretion.

PMID- 29334066
TI  - Comparative Study of Microcalorimetric Behavior of Escherichia coli, Proteus
      mirabilis and Klebsiella pneumoniae.
AB  - To analyze the microcalorimetric behaviour of Escherichia coli, Proteus mirabilis
      and Klebsiella pneumoniae, and to test the prospective use of microcalorimetry in
      the early diagnosis of infections by enterobacteria. For our experiments we used
      cultures of E. coli, P. mirabilis and K. pneumoniae. For the experimental setup,
      we used a Calvet microcalorimeter with the constant temperature of 309 K inside.
      Using the measured difference of heat power generated by the cells over time, we
      obtained growth graphs of the three bacterial species grown at different
      densities. The generated curves have characteristic plot that repeats for each
      bacterial species at all the concentrations studied. We observed an inversely
      proportional relationship between inoculum size and the time until signal
      detection; the smaller inoculum, the longer time for the signal detection. In all
      conducted experiments, even with low number of bacteria (10 CFU/ml) as inoculum,
      we could identify bacterial growth in the sample within 8 hours. Microcalorimetry
      could be an efficient technique used for the early detection and identification
      of enterobacteria in a culture medium.

PMID- 29334067
TI  - In Search of the Antimicrobial Potential of Benzimidazole Derivatives.
AB  - A broad series of 4,5,6,7-tetrahalogenated benzimidazoles and 4-(1H-benzimidazol
      2-yl)-benzene-1,3-diol derivatives was tested against selected bacteria and
      fungi. For this study three plant pathogens Colletotrichum sp., Fusarium sp., and
      Sclerotinia sp., as well as Staphylococcus sp., Enterococcus sp., Escherichia
      sp., Enterobacter sp., Klebsiella spp. , and Candida spp. as human pathogens were
      used. MIC values and/or area of growth reduction method were applied in order to
      compare the activity of the synthesized compounds. From the presented set of 22
      compounds, only 8, 16, 18 and 19 showed moderate to good inhibition against
      bacterial strains. Against Candida strains only compound 19 with three hydroxyl
      substituted benzene moiety presented high inhibition at nystatin level or lower.

PMID- 29334068
TI  - Microbial Products and Biofertilizers in Improving Growth and Productivity of
      Apple - a Review.
AB  - The excessive use of mineral fertilizers causes many negative consequences for
      the environment as well as potentially dangerous effects of chemical residues in
      plant tissues on the health of human and animal consumers. Bio-fertilizers are
      formulations of beneficial microorganisms, which upon application can increase
      the availability of nutrients by their biological activity and help to improve
      soil health. Microbes involved in the formulation of bio-fertilizers not only
      mobilize N and P but mediate the process of producing crops and foods naturally.
      This method avoids the use of synthetic chemical fertilizers and genetically
      modified organisms to influence the growth of crops. In addition to their role in
      enhancing the growth of the plants, biofertilizers can act as biocontrol agents
      in the rhizosphere at the same time. Biofertilizers are very safe for human,
      animal and environment. The use of Azotobacter, Azospirillum, Pseudomonas,
      Acetobacter, Burkholderia, Bacillus, Paenibacillus and some members of the
      Enterobacteriaceae is gaining worldwide importance and acceptance and appears to
      be the trend for the future.

PMID- 29334069
TI  - Quantitative Estimation of Porcine Endogenous Retrovirus Release from PK15 Cells.
AB  - The present study focuses on the assessment of porcine endogenous retrovirus
      (PERV) release from PK15 cells in a time dependent manner. The highest amount of
      PERV A RNA was detected in PK15 cells after 16 hours of culture. The highest
      amount of PERV B RNA was detected in PK15 cells after 20 hours. The highest
      amount of both subtypes RNAs was detected in culture medium after 32 hours of
      culture. The peaks of PERV reverse transcriptase (RT) activity were detected
      after 28 h of culture in PK15 cells and after 32 hours in the culture medium. The
      monitoring of PERV release from PK15 cell line may be useful for the evaluation
      of PERV replication.

PMID- 29334070
TI  - Ethanol Production Potential of Ethanol-Tolerant Saccharomyces and Non
      Saccharomyces Yeasts.
AB  - Four ethanologenic ethanol-tolerant yeast strains, Saccharomyces cerevisiae
      (ATKU132), Saccharomycodes ludwigii (ATKU47), and Issatchenkia orientalis (ATKU5
      60 and ATKU5-70), were isolated by an enrichment technique in yeast extract
      peptone dextrose (YPD) medium supplemented with 10% (v/v) ethanol at 30 degrees
      C. Among non-Saccharomyces yeasts, Sd. ludwigii ATKU47 exhibited the highest
      ethanol-tolerance and ethanol production, which was similar to S. cerevisiae
      ATKU132. The maximum range of ethanol concentrations produced at 37 degrees C by
      S. cerevisiae ATKU132 and Sd. ludwigii ATKU47 from an initial D-glucose
      concentration of 20% (w/v) and 28% (w/v) sugarcane molasses were 9.46-9.82% (w/v)
      and 8.07-8.32% (w/v), respectively.

PMID- 29334071
TI  - Genetic Variability and Proteome Profiling of a Radiation Induced Cellulase
      Mutant Mushroom Pleurotus florida.
AB  - We report the genetic similarity changes between a mutant mushroom (Pleurotus
      florida, designated as PfCM4) having increased cellulolytic activity developed
      through radiation mutagenesis and its wild type by amplified fragment length
      polymorphism (AFLP). On average, 23 AFLP fragments were amplified per primer
      combination, and a total of 286 polymorphic fragments (78.57% polymorphism) with
      maximal fragment length of 1365 base pairs (bp) were obtained. The genetic
      similarity between wild type and PfCM4 was found to be 22.30%. In addition,
      mycelial and secreted protein profiling by 2D-PAGE showed at least three and five
      different protein spots in the range of 25 kD to 100 kD, respectively, in PfCM4.
      It seems that the variation in genetic similarity and different expression of
      both mycelial and secreted proteins in PfCM4 in comparison to the wild type could
      likely be correlated with its increased cellulolytic activity effected by the
      irradiation.

PMID- 29334072
TI  - Basidiospore and Protoplast Regeneration from Raised Fruiting Bodies of
      Pathogenic Ganoderma boninense.
AB  - Ganoderma boninense, a phytopathogenic white rot fungus had sought minimal
      genetic characterizations despite huge biotechnological potentials. Thus,
      efficient collection of fruiting body, basidiospore and protoplast of G.
      boninense is described. Matured basidiocarp raised under the glasshouse
      conditions yielded a total of 8.3 * 104 basidiospores/ml using the low speed
      centrifugation technique. Mycelium aged 3-day-old treated under an incubation
      period of 3 h in lysing enzyme from Trichoderma harzianum (10 mg/ml) suspended in
      osmotic stabilizer (0.6 M potassium chloride and 20 mM dipotassium phosphate
      buffer) yielded the highest number of viable protoplasts (8.9 * 106 single
      colonies) among all possible combinations tested (regeneration media, age of
      mycelium, osmotic stabilizer, digestive enzyme and incubation period).

PMID- 29334073
TI  - Simultaneous Biodegradation of Phenol and n-Hexadecane by Cryogel Immobilized
      Biosurfactant Producing Strain Rhodococcus wratislawiensis BN38.
AB  - The capability of the biosurfactant-producing strain Rhodococcus wratislawiensis
      BN38 to mineralize both aromatic and aliphatic xenobiotics was proved. During
      semicontinuous cultivation 11 g/l phenol was completely degraded within 22 cycles
      by Rhodococcus free cells. Immobilization in a cryogel matrix was performed for
      the first time to enhance the biodegradation at multiple use. A stable
      simultaneous hydrocarbon biodegradation was achieved until the total depletion of
      20 g/l phenol and 20 g/l n-hexadecane (40 cycles). The alkanotrophic strain R.
      wratislawiensis BN38 preferably degraded hexadecane rather than phenol. SEM
      revealed well preserved cells entrapped in the heterogeneous super-macroporous
      structure of the cryogel which allowed unhindered mass transfer of xenobiotics.
      The immobilized strain can be used in real conditions for the treatment of
      contaminated industrial waste water.

PMID- 29334074
TI  - Effects of Selected Herbicides on Growth and Nitrogen Fixing Activity of
      Stenotrophomonas maltophilia (Sb16).
AB  - A study was carried out to determine the effects of paraquat, pretilachlor and 2,
      4-D on growth and nitrogen fixing activity of Stenotrophomonas maltophilia (Sb16)
      and pH of Jensen's N-free medium. The growth of Sb16 and pH of medium were
      significantly reduced with full (X) and double (2X) doses of tested herbicides,
      but nitrogen fixing activity was decreased by 2X doses. The nitrogenase activity
      had the highest value in samples treated with 1/2X of 2, 4-D on fifth incubation
      day, but 2X of 2, 4-D had the most adverse effect. An inhibition in the growth
      and nitrogenase activity was recovered on the last days of incubation.

PMID- 29334075
TI  - Classifying vortex wakes using neural networks.
AB  - Unsteady flows contain information about the objects creating them. Aquatic
      organisms offer intriguing paradigms for extracting flow information using local
      sensory measurements. In contrast, classical methods for flow analysis require
      global knowledge of the flow field. Here, we train neural networks to classify
      flow patterns using local vorticity measurements. Specifically, we consider
      vortex wakes behind an oscillating airfoil and we evaluate the accuracy of the
      network in distinguishing between three wake types, 2S, 2P  +  2S and 2P  +  4S.
      The network uncovers the salient features of each wake type.

PMID- 29334077
TI  - Magnitude of the current in 2D interlayer tunneling devices.
AB  - Using the Bardeen tunneling method with first-principles wave functions,
      computations are made of the tunneling current in graphene/hexagonal-boron
      nitride/graphene (G/h-BN/G) vertical structures. Detailed comparison with prior
      experimental results is made, focusing on the magnitude of the achievable tunnel
      current. With inclusion of the effects of translational and rotational
      misalignment of the graphene and the h-BN, predicted currents are found to be
      about 15*  larger than experimental values. A reduction in this discrepancy, to a
      factor of 2.5*, is achieved by utilizing a realistic size for the band gap of the
      h-BN, hence affecting the exponential decay constant for the tunneling.

PMID- 29334076
TI  - Pt decorated MoS<sub>2</sub> nanoflakes for ultrasensitive resistive humidity
      sensor.
AB  - In this work, we report the fabrication of a low power, humidity sensor where
      platinum nanoparticles (NPs) decorated few-layered Molybdenum disulphide
      (MoS<sub>2</sub>) nanoflakes have been used as the sensing layer. A mixed solvent
      was used to exfoliate the nanoflakes from the bulk powder. Then the
      Pt/MoS<sub>2</sub> composites were prepared by reducing Pt NPs from
      chloroplatinic acid hexahydrate using a novel reduction technique using sulfide
      salt. The successful reduction and composite preparation were confirmed using
      various material characterization tools like Scanning Electron Microscopy (SEM),
      Atomic Force Microscopy (AFM), Transmission Electron Microscopy (TEM), X-Ray
      Diffraction (XRD), X-ray Photoelectron Spectroscopy (XPS), Raman spectroscopy and
      UV-visible spectroscopy (UV-Vis). The humidity sensors were prepared by drop
      coating the Pt-decorated MoS<sub>2</sub> on gold interdigitated electrodes and
      then exposed to various levels of relative humidity (RH). Composites with
      different weight ratios of Pt were tested and the best response was shown by the
      Pt/MoS<sub>2</sub> (0.25:1) sample with a record high response of ~4000 times at
      85% RH. The response and recovery times were ~92 seconds and ~154 seconds
      respectively with repeatable behavior. The sensor performance was found to be
      stable when tested over a few months. The underlying sensing mechanisms along
      with detailed characterization of the various composites have been discussed.

PMID- 29334078
TI  - High PRF ultrafast sliding compound doppler imaging: fully qualitative and
      quantitative analysis of blood flow.
AB  - Ultrafast compound Doppler imaging based on plane-wave excitation (UCDI) can be
      used to evaluate cardiovascular diseases using high frame rates. In particular,
      it provides a fully quantifiable flow analysis over a large region of interest
      with high spatio-temporal resolution. However, the pulse-repetition frequency
      (PRF) in the UCDI method is limited for high-velocity flow imaging since it has a
      tradeoff between the number of plane-wave angles (N) and acquisition time. In
      this paper, we present high PRF ultrafast sliding compound Doppler imaging method
      (HUSDI) to improve quantitative flow analysis. With the HUSDI method, full
      scanline images (i.e. each tilted plane wave data) in a Doppler frame buffer are
      consecutively summed using a sliding window to create high-quality ensemble data
      so that there is no reduction in frame rate and flow sensitivity. In addition, by
      updating a new compounding set with a certain time difference (i.e. sliding
      window step size or L), the HUSDI method allows various Doppler PRFs with the
      same acquisition data to enable a fully qualitative, retrospective flow
      assessment. To evaluate the performance of the proposed HUSDI method, simulation,
      in vitro and in vivo studies were conducted under diverse flow circumstances. In
      the simulation and in vitro studies, the HUSDI method showed improved hemodynamic
      representations without reducing either temporal resolution or sensitivity
      compared to the UCDI method. For the quantitative analysis, the root mean squared
      velocity error (RMSVE) was measured using 9 angles (-12 degrees  to 12 degrees )
      with L of 1-9, and the results were found to be comparable to those of the UCDI
      method (L  =  N  =  9), i.e.  ?0.24 cm s-1, for all L values. For the in vivo
      study, the flow data acquired from a full cardiac cycle of the femoral vessels of
      a healthy volunteer were analyzed using a PW spectrogram, and arterial and venous
      flows were successfully assessed with high Doppler PRF (e.g. 5 kHz at L  =  4).
      These results indicate that the proposed HUSDI method can improve flow
      visualization and quantification with a higher frame rate, PRF and flow
      sensitivity in cardiovascular imaging.

PMID- 29334079
TI  - First heating measurements of endovascular stents in magnetic particle imaging.

PMID- 29334080
TI  - Effects of microarchitecture and mechanical properties of 3D microporous PLLA
      PLGA scaffolds on fibrochondrocyte and L929 fibroblast behavior.
AB  - There are several reports studying cell behavior on surfaces in 2D or in
      hydrogels in 3D. However, cell behavior in 3D microporous scaffolds has not been
      investigated extensively. In this study, poly(L-lactic acid)/poly(lactic acid-co
      glycolic acid) (PLLA/PLGA)-based microporous scaffolds were used to study the
      effects of scaffold microarchitecture and mechanical properties on the behavior
      of two different cell types, human meniscal fibrochondrocytes and L929 mouse
      fibroblasts. In general, cell attachment, spreading and proliferation rate were
      mainly regulated by the strut (pore wall) stiffness. Increasing strut stiffness
      resulted in an increase in L929 fibroblast attachment and a decrease in
      fibrochondrocyte attachment. L929 fibroblasts tended to get more round as the
      strut stiffness increased, while fibrochondrocytes tended to get more elongated.
      Cell migration increased for both cell types with the increasing pore size.
      Migrating L929 fibroblasts tended to get more round on the stiff scaffolds, while
      fibrochondrocytes tended to get more round on the soft scaffolds. This study
      shows that the behavior of cells on 3D microporous scaffolds is mainly regulated
      by pore size and strut stiffness, and the response of a cell depends on the
      stiffness of both cells and materials. This study could be useful in designing
      better scaffolds for tissue engineering applications.

PMID- 29334081
TI  - Bio-inspired all-optical artificial neuromast for 2D flow sensing.
AB  - We present the design, fabrication and testing of a novel all-optical 2D flow
      velocity sensor, inspired by a fish lateral line neuromast. This artificial
      neuromast consists of optical fibres inscribed with Bragg gratings supporting a
      fluid force recipient sphere. Its dynamic response is modelled based on the
      Stokes solution for unsteady flow around a sphere and found to agree with
      experimental results. Tuneable mechanical resonance is predicted, allowing a
      deconvolution scheme to accurately retrieve fluid flow speed and direction from
      sensor readings. The optical artificial neuromast achieves a low frequency
      threshold flow sensing of 5 mm s-1 and 5 MUm s-1 at resonance, with a typical
      linear dynamic range of 38 dB at 100 Hz sampling. Furthermore, the optical
      artificial neuromast is shown to determine flow direction within a few degrees.

PMID- 29334083
TI  - Solvated-electron production using cyanocuprates is compatible with the UV
      environment on a Hadean-Archaean Earth.
AB  - UV-driven photoredox processing of cyanocuprates can generate simple sugars
      necessary for prebiotic synthesis. We investigate the wavelength dependence of
      this process from 215 to 295 nm and generally observe faster rates at shorter
      wavelengths. The most efficient wavelengths are accessible to a range of
      potential prebiotic atmospheres, supporting the potential role of cyanocuprate
      photochemistry in prebiotic synthesis on the early Earth.

PMID- 29334082
TI  - Economic costs due to workers' sick leave at wastewater treatment plants in
      Bulgaria.
AB  - BACKGROUND: The compensatory mechanisms of social security include expenses for
      sick leave. The aim of the study is to determine the economic cost due to sick
      leave among workers in wastewater treatment plants (WWTPs), comparing with the
      same economic indicators of the National Social Security Institute (NSSI) in
      Bulgaria. MATERIAL AND METHODS: The sick leave of 111 workers at 3 WWTPs was
      studied in the period 2012-2014 on the grounds of registered absences from work
      due to temporary incapacity for work. The economic indicators of the NSSI, the
      gross salary at WWTPs, payable social security contributions and compensatory
      payments for sick leave have been used for economic cost calculation for
      temporary incapacity of the workers. RESULTS: The frequency of cases and the
      frequency of lost days due to temporary incapacity were increased in the observed
      period at WWTPs and in Bulgaria, and it is significantly higher for the employed
      at WWTPs. The percentage share of workers equivalent to 1.66% at WWTPs have not
      worked for an entire year as a result of temporary incapacity in 2012, 2.76% - in
      2013, and 4.61% - in 2014. The economic burden due to sick leave at WWTPs was
      raised from EUR 4913.02 in 2012 to EUR 16 895.80 for 2014 for employers and the
      NSSI. CONCLUSIONS: The frequency of cases and the frequency of lost days due to
      temporary incapacity were increased in the observed period at WWTPs and in
      Bulgaria, and it is significantly higher for the employed at WWTPs. The economic
      burden was equally distributed between employers and the NSSI. Med Pr
      2018;69(2):129-141.

PMID- 29334085
TI  - SpyCatcher-SpyTag mediated in situ labelling of progeny baculovirus with quantum
      dots for tracking viral infection in living cells.
AB  - A non-invasive labelling strategy is proposed to label baculovirus via genetic
      insertion of a SpyTag into the viral glycoprotein, followed by specific
      conjugation with the SpyCatcher protein on modified quantum dots (QDs) through an
      isopeptide bond. The labelling method is convenient and efficient and shows
      little attenuation of viral infectivity. Therefore, it is a biologically
      compatible technique for tracking viral infection.

PMID- 29334084
TI  - A cyanine-based fluorescent cassette with aggregation-induced emission for
      sensitive detection of pH changes in live cells.
AB  - An aggregation-induced emission (AIE) cyanine-based fluorescent cassette with a
      large pseudo-Stokes shift was designed and prepared to sensitively image pH
      changes in live cells via through-bond energy transfer (TBET) from a
      tetraphenylethene (TPE) donor to a cyanine acceptor.

PMID- 29334086
TI  - N-Doped graphene-supported PdCu nanoalloy as efficient catalyst for reducing
      Cr(vi) by formic acid.
AB  - Reducing Cr(vi) to Cr(iii) with formic acid is desirable for environmental
      protection, but the sluggish kinetics limits its practical application, which
      currently motivates the intensive study of efficient catalysts for this redox
      reaction. Here bimetallic PdCu nanoalloy (~5 nm in size) supported by N-doped
      graphene was synthesized through a one-pot hydrothermal process. The catalytic
      activity of PdCu nanoalloy highly depends on the Pd/Cu atomic ratio and N-doped
      graphene support. The obtained Pd6Cu4/NG shows superior catalysis towards the
      Cr(vi) reduction by formic acid with a high kinetic constant (kn = 23.2 min-1 mg
      1) and a low activation energy (Ea = 34.9 kJ mol-1). Active H atoms were found to
      be the exact reductant for the Cr(vi) reduction, quite different from the
      reported H2-reduction route. The enhanced catalysis originates from the
      electronic and geometric modification of active Pd after formation of PdCu alloy.
      Electron transfer from Cu to Pd enhances the electron density of Pd atoms, which
      favors the adsorption of the bridging formate intermediate and subsequent
      generation of active H atoms over PdCu/NG. The catalyst can be recycled five
      times without obvious loss of activity. Our work provides an example to explore
      the alloying effect on the catalytic behavior of PdCu alloy, which may shed light
      on developing other advanced nanoalloys for Cr(vi) reduction.

PMID- 29334087
TI  - Achiral non-fluorescent molecule assisted enhancement of circularly polarized
      luminescence in naphthalene substituted histidine organogels.
AB  - A naphthalene substituted histidine derivative was found to form an organogel
      showing circularly polarized luminescence (CPL) and the addition of non
      fluorescent achiral benzoic acids could efficiently enhance the CPL via non
      covalent interactions.

PMID- 29334088
TI  - Chemically accurate adsorption energies for methane and ethane monolayers on the
      MgO(001) surface.
AB  - A hybrid QM:QM method that combines MP2 as high-level method on cluster models
      with density functional theory (PBE+D2) as low-level method on periodic models is
      applied to adsorption of methane and ethane on the MgO(001) surface for which
      reliable experimental desorption enthalpies are available. Two coverages are
      considered, monolayer (every second Mg2+ ion occupied) and one quarter coverage
      (one of eight Mg2+ ions occupied). Structure optimizations are performed at the
      hybrid MP2:(PBE+D2) level, with the MP2 energies and forces counterpoise
      corrected for basis set superposition error and extrapolated to the complete
      basis set limit. For the MP2 calculations on the adsorbate monolayer a two-body
      expansion of the lateral molecule-molecule interactions is applied. Higher order
      correlation effects are evaluated at the hybrid MP2:(PBE+D2) equilibrium
      structures as coupled cluster [CCSD(T)] - MP2 differences adopting smaller basis
      sets. The final adsorption energies obtained for monolayer coverage are -14.0 +/-
      1.0 and -23.3 +/- 0.6 kJ mol-1 for CH4.MgO(001) and C2H6.MgO(001), respectively.
      They agree within 1 kJ mol-1 - well within chemical accuracy limits - with
      reference energies of -15.0 +/- 0.6 and -24.4 +/- 0.6 kJ mol-1, respectively. The
      latter have been derived from measured desorption enthalpy barriers, taking zero
      point vibrational energy (ZPVE) and thermal enthalpy contributions into account.

PMID- 29334089
TI  - Asymmetric [4+2] annulations to construct norcamphor scaffolds with 2
      cyclopentenone via double amine-thiol catalysis.
AB  - An efficient double catalytic system, combining chiral amine and 2
      mercaptobenzoic acid, is applied for alpha',beta-regioselective [4+2] annulations
      of 2-cyclopentenone with a diversity of activated alkenes, constructing
      multifunctional chiral bicycle[2,2,1]heptane scaffolds in good to excellent
      yields and enantioselectivities. In comparison with the traditional cross
      dienamine species between 2-cyclopentenone and chiral amine, the interrupted
      enamine intermediate containing a covalently linked thiol catalyst shows
      significantly improved reactivity.

PMID- 29334090
TI  - Supramolecular photosensitizers rejuvenate photodynamic therapy.
AB  - Owing to its spatiotemporal selectivity and noninvasive nature, photodynamic
      therapy (PDT) has become a clinically promising approach for the treatment of a
      wide range of cancers and other diseases. However, the full potential of PDT has
      not been achieved thus far as a consequence of the lack of optimal
      photosensitizers (PSs) and/or smart transport/activation strategies. These
      problems, which unfortunately lie at the core of the PDT paradigm, include the
      oxygen reliance limits, the effect of PDT on hypoxic tumors, limitations of light
      penetration, and undesired skin photosensitization induced by "always on" PSs.
      Recently, supramolecular approaches, which rely on the use of non-covalent
      interactions to construct biomedical active materials, have become suitable
      methods for developing innovative PSs. Non-covalent interactions enable
      supramolecular PSs to have sensitive and controllable photoactivities, important
      elements needed to maximize photodynamic effects and minimize side effects. In
      addition, versatile supramolecular PS-assemblies can be designed so that PDT
      occurs synergistically with other therapeutic modalities, e.g., photothermal
      therapy, leading to a potential improvement of therapeutic effectiveness. In this
      review, recent progress made in the development of supramolecular PSs for
      rejuvenating PDT will be presented. Importantly, this discussion also provides a
      view of future advances that will likely be made in this area and their potential
      clinical applications.

PMID- 29334091
TI  - Selectivity shift from paraffins to alpha-olefins in low temperature Fischer
      Tropsch synthesis in the presence of carboxylic acids.
AB  - A shift of selectivity to long chain alpha-olefins has been observed during
      Fischer-Tropsch synthesis over Co catalysts in the presence of carboxylic acids.
      The total selectivity to alpha-olefins of 39% was obtained in the presence of
      acids. The effect has been ascribed to intermediate formation of esters which
      hinder secondary olefin hydrogenation.

PMID- 29334092
TI  - Synthetic cells produce a quorum sensing chemical signal perceived by Pseudomonas
      aeruginosa.
AB  - Recent developments in bottom-up synthetic biology (e.g., lipid vesicle
      technology integrated with cell-free protein expression systems) allow the
      generation of semi-synthetic minimal cells (in short, synthetic cells, SCs)
      endowed with some distinctive capacities of natural cells. In particular, such
      approaches provide technological tools and conceptual frameworks for the design
      and engineering of programmable SCs capable of communicating with natural cells
      by exchanging chemical signals. Here we describe the generation of giant vesicle
      based SCs which, via gene expression, synthesize in their aqueous lumen an enzyme
      that in turn produces a chemical signal. The latter is a small molecule, which is
      passively released in the medium and then perceived by the bacterium Pseudomonas
      aeruginosa, demonstrating that SCs and bacteria can communicate chemically. The
      results pave the way to a novel basic and applied research area where synthetic
      cells can communicate with natural cells, for example for exploring minimal
      cognition, developing chemical information technologies, and producing smart and
      programmable drug-producing/drug-delivery systems.

PMID- 29334093
TI  - Three-component difluoroalkylation and
      trifluoromethylthiolation/trifluoromethylselenolation of pi-bonds.
AB  - This report describes a new method for three-component difluoroalkylation and
      trifluoromethylthiolation/trifluoromethylselenolation of pi-bonds via air-stable
      SCF3 and SeCF3 reagents as free-radical initiators of ethyl iododifluoroacetate.
      beta-Proton elimination can be overcome effectively in this reaction system, and
      a broad substrate scope, including alkenes and alkynes, makes this approach
      practical and attractive.

PMID- 29334094
TI  - Nine-step total synthesis of (-)-strychnofoline.
AB  - Strychnofoline is a Strychnos alkaloid that has unique spirooxindole architecture
      and possesses important anticancer activity. Here, we have, for the first time,
      reported the enantioselective synthesis of strychnofoline proceeding in only nine
      steps from commercially available 6-methoxytryptamine. The efficiency of the
      synthesis derives from the use of two sequential transformation steps in the
      catalytic asymmetric construction of the spiro[pyrrolidine-3,3'-oxindole] motif
      in a facile manner. Our route is amenable to the synthesis of other natural and
      synthetic analogs of bioactive spirooxindole alkaloids to access their
      therapeutic potential.

PMID- 29334095
TI  - Gd3+-Doped MoSe2 nanosheets used as a theranostic agent for bimodal imaging and
      highly efficient photothermal cancer therapy.
AB  - Recently, two dimensional transition metal dichalcogenides (TMDCs) being used as
      nanomedicine have aroused great interest because of their unique photothermal
      properties. A simple liquid-phase method was used to prepare gadolinium (Gd3+)
      doped molybdenum selenide (MoSe2) nanosheets, and then using poly(ethylene
      glycol) (PEG) modification on the surface, MoSe2(Gd3+)-PEG nanosheets were
      obtained which had high stability in physiological solutions and showed no
      obvious toxicity in vivo. It revealed that Gd3+ used as a paramagnetic material
      for MoSe2(Gd3+)-PEG provided a strong contrast effect in magnetic resonance
      imaging, furthermore, the MoSe2 showed strong absorption in the near infrared
      region, and therefore, MoSe2(Gd3+)-PEG could be used as contrast agent for
      photoacoustic imaging (PAI). In in vitro experiments, it was found that
      MoSe2(Gd3+)-PEG could effectively increase the temperature to help kill cancer
      cells under laser irradiation. In vivo experiments showed that there was an
      enhanced permeation and retention effect in the tumor after intravenous injection
      measured using magnetic resonance/photoacoustic (MR/PA) bimodal imaging. After
      photothermal therapy, a significant suppression effect was achieved for tumors in
      mice by injection of these nanosheets with laser irradiation. This work
      emphasized that the simple doped TMDC nanomaterials when combined with treatment
      and imaging functions achieve a cancer therapy, which will provide a good
      opportunity for future diagnosis and treatment of cancer.

PMID- 29334096
TI  - Microwave-induced covalent functionalization of few-layer graphene with arynes
      under solvent-free conditions.
AB  - A non-conventional modification of exfoliated few-layer graphene (FLG) with
      different arynes under microwave (MW) irradiation and solvent-free conditions is
      reported. The described approach allows reaching fast, efficient and mild
      covalent functionalization of FLG.

PMID- 29334097
TI  - Artificial light-harvesting supramolecular polymeric nanoparticles formed by
      pillar[5]arene-based host-guest interaction.
AB  - Artificial light-harvesting nanoparticles were prepared from supramolecular
      polymers comprised of pillar[5]arene with anthracene-derived donors and acceptors
      through host-guest interactions. The resulting water-dispersible nanoparticles
      displayed efficient energy transfer and excellent light harvesting ability in
      part because the steric bulk of pillar[5]arene suppressed the self-quenching of
      the chromophores.

PMID- 29334098
TI  - How a tertiary diamine molecule chelates the silicon dimers of the Si(001)
      surface: a real-time scanning tunneling microscopy study.
AB  - The patterning of silicon surfaces by organic molecules emerges as an original
      way to fabricate innovative nanoelectronic devices. In this regard, we have
      studied how a diamine, N,N,N',N'-tetramethylethylenediamine (TMEDA, (CH3)2N
      [CH2]2-N(CH3)2), chelates the silicon dimers of the Si(001)-2 * 1 surface.
      Starting from very low coverage to surface saturation (at 300 K), we used real
      time scanning tunneling microscopy (STM) in a scanning-while-dosing approach. The
      images show that the molecules can adopt two bonding configurations: the cross
      trench (CT) configuration by bridging two adjacent dimer rows, and the end-bridge
      (EB) configuration by chelating two adjacent dimers in the same row. However,
      while CT dominates over EB at low coverage, the percentage of EB adducts steadily
      increases, until it becomes largely dominant at high molecular coverage. Above a
      critical coverage thetamol of ~0.13 monolayer (ML), a sudden change in the
      molecular imprints is seen, likely due to a change in the tunneling conditions.
      The EB stapling of two adjacent dimers in a row via a dual-dative bond (as shown
      by XPS) is achieved efficiently by the TMEDA molecule with a very high chemical
      selectivity. The EB is a unique configuration in amine adsorption chemistry, as
      it leads to the formation of a pair of first-neighbor, doubly-occupied dangling
      bonds. Further reactivity of the EB site with other molecules remains to be
      explored, and possible reaction schemes are envisaged.

PMID- 29334099
TI  - Composition-dependent emission linewidth broadening in lead bromide perovskite
      (APbBr3, A = Cs and CH3NH3) nanoparticles.
AB  - Lead halide perovskite nanoparticles (NPs) are attractive as they exhibit
      excellent color purity and have a tunable band gap, and can thus be applied in
      highly efficient photovoltaic and light-emitting diodes. Fundamental studies of
      emission linewidth broadening due to spectral shifts in perovskite NPs may
      suggest a way to improve their color purity. However, the carrier-induced Stark
      shift that causes spectral diffusion still requires investigation. In this study,
      we explore composition-related emission linewidth broadening by comparing CsPbBr3
      and CH3NH3PbBr3 (MAPbBr3) perovskite NPs. We find that the MAPbBr3 NPs are more
      sensitive to fluctuations in the local electric fields than the CsPbBr3 NPs due
      to an intrinsic difference in the dipole moment between the two A cations (Cs and
      MA), which shows a carrier-induced Stark shift. The results indicate that the
      compositions of perovskite NPs are closely associated with emission linewidth
      broadening and they also provide insights into the development of NP-based
      devices with high color purity.

PMID- 29334100
TI  - First-principles simulation of local response in transition metal dichalcogenides
      under electron irradiation.
AB  - Electron beam irradiation by transmission electron microscopy (TEM) is a common
      and effective method for post-synthesis defect engineering in two-dimensional
      transition metal dichalcogenides (TMDs). Combining density functional theory
      (DFT) with relativistic scattering theory, we simulate the generation of such
      defects in monolayer group-VI TMDs, MoS2, WS2, MoSe2, and WSe2, focusing on two
      fundamental TEM-induced atomic displacement processes: chalcogen sputtering and
      chalcogen vacancy migration. Our calculations show that the activation energies
      of chalcogen sputtering depend primarily on the chalcogen species, and are
      smaller in selenides than in sulfides. Meanwhile, chalcogen vacancy migration
      activation energies hinge on the transition metal species, being smaller in TMDs
      containing Mo. Incorporating these energies into a relativistic, temperature
      dependent cross section, we predict that, with appropriate TEM energies and
      temperatures, one can induce migrations in all four group-VI TMDs without
      simultaneously producing vacancies at a significant rate. This can allow for the
      formation of complicated defects and extended patterns, and thus, for the
      controlled manipulation of TMD crystals for targeted functionality, without the
      risk of substantial collateral damage.

PMID- 29334101
TI  - Semiconductor-metal structural phase transformation in MoTe2 monolayers by
      electronic excitation.
AB  - Optical modulation of the crystal structure and materials properties is an
      increasingly important technique for functionalization of two-dimensional and
      layered semiconductors, where traditional methods like chemical doping are
      ineffective. Controllable transformation between the semiconducting (H) and
      semimetallic (T') polytypes of transition metal chalcogenide monolayers is of
      central importance to two-dimensional electronics, and thermally-driven and
      strain-driven examples of this phase transformation have been previously
      reported. However, the possibility of a H-T' phase transformation driven by
      electronic or optical excitation is less explored and little is known about the
      potential energy surface and the magnitude of activation barriers or the
      mechanism of the phase transformation in the excited state. Here, we model the
      electronic and ionic structure of excited MoTe2 crystals and demonstrate how
      electronic excitation leads to a Fermi-surface-nesting driven softening of phonon
      modes at the Brillouin zone boundary and the subsequent stabilization of a low
      energy intermediate crystal structure along the semiconductor-metal phase
      transition pathway. The significantly reduced barriers for this transformation
      upon electronic excitation suggest that optical excitation may enable rapid and
      controllable synthesis of lateral semiconductor-metal heterophase homojunctions
      in monolayer materials for use in next-generation two-dimensional nano
      electronics applications.

PMID- 29334102
TI  - Ru nanoparticles dispersed on magnetic yolk-shell nanoarchitectures with Fe3O4
      core and sulfoacid-containing periodic mesoporous organosilica shell as
      bifunctional catalysts for direct conversion of cellulose to isosorbide.
AB  - A green and sustainable approach for biorefining involves the development of
      bifunctional catalysts for the one-pot conversion of cellulosic biomass to
      isosorbide. This requires highly efficient, easily separated and versatile metal
      acid catalysts for hydrolysis-hydrogenation-dehydration cascade reactions.
      Herein, we report a new type of metal-acid bifunctional catalyst by dispersing Ru
      nanoparticles (NPs) on magnetic yolk-shell nanoarchitectures comprising an Fe3O4
      core and a sulfoacid (SO3H)-containing periodic mesoporous organosilica shell.
      The resultant magnetic Ru-SO3H nanoreactors are highly porous and have large
      surface areas (>350 m2 g-1), uniform mesopores (~3.8 nm), well-dispersed Ru NPs
      (<1.5 wt%) and superior magnetization. Tailoring the size of the Ru NPs and the
      amount of SO3H moieties produced a highly efficient Ru-SO3H nanocatalyst, which
      delivered a high yield of isosorbide of 58.1% with almost complete conversion of
      cellulose in 2 h and achieved maximum productivity of 2.19 molIsosor h-1 gRu-1,
      which was one order of magnitude higher than that achieved using other Ru
      containing acidic catalysts. Moreover, the elaborately fabricated Ru-SO3H
      nanocatalyst can be easily separated by applying an external magnetic field and
      can be cycled four times. This work reveals new possibilities for the fabrication
      of highly efficient, easily separated metal-acid catalysts in virtue of the
      concept of nanoreactor design.

PMID- 29334103
TI  - Unexpected cleavage of upper rim-bridged calix[4]arenes leading to linear
      oligophenolic derivatives.
AB  - Regioselective meta-mercuration followed by Pd-catalysed intramolecular bridging
      gave birth to a novel type of calixarene bearing a single bond bridge between the
      meta positions of the neighboring aromatic subunits. These bridged derivatives
      possess extremely distorted cavities that imply possible amended properties over
      common calix[4]arenes. This new type of calixarene reactivity can be documented
      by acid-/electrophile-mediated cleavage of the basic macrocyclic skeleton leading
      to open oligomeric structures-the behavior of which has never been observed
      before in classic calix[4]arenes bearing alkoxy groups on the lower rim.

PMID- 29334104
TI  - One-pot cascade synthesis of azabicycles via the nitro-Mannich reaction and N
      alkylation.
AB  - A one-pot, metal-free process for the synthesis of azabicycles is developed. The
      key transformations involved a cascade of double intramolecular cyclizations via
      the nitro-Mannich reaction and N-alkylation, providing various ring systems of
      azabicycles in yields up to 81% and an isomeric ratio of 62 : 1. This approach
      offers considerable advantages in terms of the handling of small molecules, the
      flexibility to introduce a functionalized side chain, and gives direct access to
      various azabicycles.

PMID- 29334105
TI  - Specific labeling of mitochondria of Chlamydomonas with cationic helicene
      fluorophores.
AB  - Twelve cationic helicenes and one triangulene were tested for the specific
      labeling of mitochondria from algal cells. Octyl ester derivative 5 readily
      penetrates algal cells and gives rise to clear fluorescence patterns when it is
      used at concentrations in the MUM range. Under these conditions, cell structures
      are well preserved and cell survival is not compromised. Cationic helicene
      compounds such as 5 provide new useful tools for examining the mitochondrial
      network and its dynamics including fission and fusion events.

PMID- 29334106
TI  - Large-scale preparation of a 3D patchy surface with dissimilar dendritic
      amphiphiles.
AB  - We show here the first example of the large-scale surface decoration of a
      macroscopic and porous monolith with dissimilar micropatches. Branched
      polyethylenimine (PEI) is alkylated with poly(propylene glycol) (PPG), leading to
      a reverse-micelle-like dendritic amphiphile of PEI@PPG. Peralkylation and partial
      quaternization of the residual amino groups of PEI@PPG produces a cationic
      dendritic amphiphile of PEI-N+@PPG. The two dendritic amphiphiles jointly
      stabilize a water-in-oil high-internal-phase emulsion to prepare open-cellular
      monoliths of macroscopic size, with the monolith pore surface dictated by the
      cationic and neutral dendritic amphiphiles. The amino groups of the neutral
      amphiphile are further derivatized into anionic dithiocarbamates. The resulting
      monolith, along with the dissimilar functional patches on the surface,
      simultaneously eliminates multiple anionic and cationic micropollutants from
      water to very low residues, and affords the pH-triggered sequential release. Our
      strategy of using dissimilar dendritic amphiphiles rather than block copolymers
      as surface building blocks can confer the resulting surface with robust and
      predesigned microenvironments besides the conventional coacervate structure, and
      thus can afford more functions.

PMID- 29334108
TI  - Porous layered stacked MnCo2O4 cubes with enhanced electrochemical capacitive
      performance.
AB  - The development of new electrode materials with various components, structures,
      morphologies and porosities is critical for improving the performance of
      supercapacitors. Here, we report a facile strategy for synthesizing porous
      layered stacked MnCo2O4 cubes through a hydrothermal method, followed by
      annealing treatment. Compared with other morphologies of MnCo2O4, the specific
      capacitance of porous layered stacked MnCo2O4 cubes reaches 480.5 F g-1 at a
      current density of 1 A g-1. Furthermore, porous layered stacked MnCo2O4 cubes
      show an ultrahigh capacity retention of 75.7% even at a current density of 25 A g
      1 and good cycling stability with 96.6% specific capacitance retained after 3000
      cycles, which makes porous layered stacked MnCo2O4 cubes a great potential
      electrode material for supercapacitor applications.

PMID- 29334109
TI  - A multifunctional supramolecular hydrogel: preparation, properties and molecular
      assembly.
AB  - A novel supramolecular hydrogel was designed and constructed by molecular self
      assembly of a cationic gemini surfactant, 1,3-bis(N,N-dimethyl-N-cetylammonium)-2
      propylacrylate dibromide (AGC16), and an anionic aromatic compound, trisodium
      1,3,6-naphthalenetrisulfonate (NTS). Owing to its unique structure, the hydrogel
      (abbreviated as AGC16/NTS) has the potential to be used as a multifunctional drug
      delivery system. The structure and properties of AGC16/NTS were characterized by
      rheological measurements, differential scanning calorimetry, variable-temperature
      1H nuclear magnetic resonance, ultraviolet-visible spectroscopy, variable
      temperature fluorescence emission spectroscopy, cryogenic scanning electron
      microscopy, transmission electron microscopy and X-ray diffraction methods. The
      rheological and DSC analysis results revealed that the gel AGC16/NTS was formed
      below 57  degrees C. It was found from UV-vis, fluorescence and 1H NMR
      spectroscopy characterization that aromatic pi-pi stacking and hydrophobic forces
      were indispensable to the formation of AGC16/NTS. The Cryo-SEM and TEM
      observation results indicated that gelators AGC16 and NTS self-assembled into one
      dimensional fibers which further tightly intertwined to form a three-dimensional
      network structure. Based on the spectroscopic data and X-ray diffraction
      measurement results, a self-assembly model was proposed, helping to further
      understand the molecular self-assembly mechanism of AGC16/NTS. It was also found
      that the electrostatic force, hydrophobic force and pi-pi interaction were the
      three main driving forces for the gelation. The multiple non-covalent
      interactions between AGC16 and NTS endowed the hydrogel with excellent
      performance when the hydrogel was used as a carrier for drug delivery, due to
      multiple micro-domains within the same gel system. We further investigated the
      encapsulation and releasing properties of the hydrogel, using the hydrophobic
      model drug curcumin (Cur) and the model drug naproxen sodium (Npx) with aromatic
      ring structure. The fluorescence spectroscopy analysis confirmed that Npx was
      carried through aromatic pi-pi stacking and the 1H NMR measurement result
      revealed that Cur was encapsulated within the hydrophobic cavities of AGC16/NTS
      through hydrophobic interaction. Moreover, the drug release study results showed
      a sustained release of drugs from the hydrogel, indicating good application
      prospects in exploring new multifunctional drug delivery systems.

PMID- 29334111
TI  - Constructing two-dimensional CuFeSe2@Au heterostructured nanosheets with an
      amorphous core and a crystalline shell for enhanced near-infrared light water
      oxidation.
AB  - Although substantial efforts have been made toward the synthesis of noble metal
      semiconductor heteronanostructures, direct in situ synthesis of two-dimensional
      (2D) core-shell semiconductor@noble metal heterostructured nanosheets remains
      largely unexplored. Herein, we report the synthesis of a novel 2D core-shell
      CuFeSe2@Au heterostructured nanosheet with an amorphous core and a crystalline
      shell based on the reversed growth of Au nanosheets on the CuFeSe2 frameworks
      under near-infrared (NIR) illumination. The nanosheet exhibits strong absorbance
      in the NIR region, and the valence band top of CuFeSe2@Au nanosheets is higher
      than the oxidation potential of O2/H2O. Owing to the unique structural features,
      the resulting nanosheets show excellent photocatalytic activity and high
      stability toward water oxidation with an O2 generation rate up to 3.48 mmol h-1 g
      1 compared to those of the constituent materials under NIR light irradiation
      (lambda > 850 nm). This work brings new opportunities to prepare 2D core-shell
      semiconductor@noble metal heterostructured nanosheets, which can be applied as
      photocatalysts toward water splitting and solar energy conversion at long
      wavelengths.

PMID- 29334114
TI  - Sensing local pH and ion concentration at graphene electrode surfaces using in
      situ Raman spectroscopy.
AB  - We report a novel approach to probe the local ion concentration at graphene/water
      interfaces using in situ Raman spectroscopy. Here, the upshifts observed in the G
      band Raman mode under applied electrochemical potentials are used to determine
      the charge density in the graphene sheet. For voltages up to +/-0.8 V vs. NHE, we
      observe substantial upshifts in the G band Raman mode by as much as 19 cm-1,
      which corresponds to electron and hole carrier densities of 1.4 * 1013 cm-2 and
      Fermi energy shifts of +/-430 meV. The charge density in the graphene electrode
      is also measured independently using the capacitance-voltage characteristics
      (i.e., Q = CV), and is found to be consistent with those measured by Raman
      spectroscopy. From charge neutrality requirements, the ion concentration in
      solution per unit area must be equal and opposite to the charge density in the
      graphene electrode. Based on these charge densities, we estimate the local ion
      concentration as a function of electrochemical potential in both pure DI water
      and 1 M KCl solutions, which span a pH range from 3.8 to 10.4 for pure DI water
      and net ion concentrations of +/-0.7 mol L-1 for KCl under these applied
      voltages.

PMID- 29334115
TI  - Label-free multidimensional information acquisition from optogenetically
      engineered cells using a graphene transistor.
AB  - The optogenetic technique, which allows the manipulation of cellular activity
      patterns in space and time by light, has transformed the field of neuroscience.
      However, acquiring multidimensional optogenetic information remains challenging
      despite the fact that several cellular information detection methods have been
      proposed. Herein, we present a new method to acquire label-free multidimensional
      information from optogenetically engineered cells using a graphene transistor.
      Using a graphene film to form a strong densely packed layer with cells, the
      cellular action potentials were characterized as light-activated transistor
      conductance signals, which quantified the multidimensional optogenetic
      information. Based on this approach, some important cellular optogenetic
      information, including electrophysiological state, cell concentration, expression
      levels of opsin and response to variable light intensity, were also precisely
      detected. Furthermore, the graphene transistor was also used to distinguish cells
      expressing different channelrhodopsin-2 variants. Our study offers a general
      detection method of multidimensional optogenetic information for extending the
      applications of the optogenetic technique and provides a novel sensor for the
      development of future biological prosthetic devices.

PMID- 29334116
TI  - Interface engineering of a CeO2-Cu3P nanoarray for efficient alkaline hydrogen
      evolution.
AB  - It is of great importance to design and develop highly active electrocatalysts
      for the hydrogen evolution reaction (HER) under alkaline conditions. In this
      work, we report the development of a CeO2-Cu3P nanoarray supported on nickel foam
      (CeO2-Cu3P/NF) as an excellent HER catalyst with the demand of an overpotential
      of only 148 mV to deliver a geometrical catalytic current density of 20 mA cm-2
      in 1.0 M KOH. Remarkably, this catalyst also shows strong long-term
      electrochemical durability for at least 100 h with nearly 100% Faradaic
      efficiency. Density functional theory calculations reveal that the CeO2-Cu3P/NF
      hybrid has a lower water dissociation energy and a more thermo-neutral hydrogen
      adsorption free energy.

PMID- 29334117
TI  - The relationship between office type and job satisfaction: Testing a multiple
      mediation model through ease of interaction and well-being.
AB  - Objectives This cross-sectional study investigated the associations between
      office type (cellular, shared-room, small open-plan, and medium-sized open-plan)
      and employees' ease of interaction with coworkers, subjective well-being, and job
      satisfaction. Methods A brief survey including measures of office type, ease of
      interaction with coworkers, subjective well-being, and job satisfaction was sent
      electronically to 1500 Swedish real-estate agents, 271 of whom returned usable
      surveys. The data were analyzed using a regression-based serial multiple
      mediation model (PROCESS Model 6), which tested whether the relationship between
      office type and job satisfaction would be mediated by ease of interaction and, in
      turn, subjective well-being. Results A negative relationship was found between
      the number of coworkers sharing an office and employees' job satisfaction. This
      association was serially mediated by ease of interaction with coworkers and
      subjective well-being, with employees working in small and medium-sized open-plan
      offices reporting lower levels of both these aspects than employees who work in
      either cellular or shared-room offices. Conclusions Open-plan offices may have
      short-term financial benefits, but these benefits may be lower than the costs
      associated with decreased job satisfaction and well-being. Therefore, decision
      makers should consider the impact of office type on employees rather than
      focusing solely on cost-effective office layout, flexibility, and productivity.

PMID- 29334118
TI  - Markers of proliferation and invasiveness in somatotropinomas.
AB  - Introduction In the search for markers of invasiveness of pituitary adenomas, we
      studied the expression of Ki-67 antigen, TOPO 2A (topoisomerase 2 alpha), AIP
      (Aryl Hydrocarbon Receptor-Interacting Protein) and VEGF (Vascular Endothelial
      Growth Factor) in somatotropinomas. Material and Methods We retrospectively
      studied a group of 31 patients who underwent pituitary tumour surgery. Expression
      of Ki-67, TOPO 2A, AIP and VEGF in surgical specimens was determined by
      immunohistochemistry. Relations between quantitatively determined markers and
      clinical symptoms, tumour features, and MR imaging, were analysed. Acromegaly was
      confirmed by hormonal tests in all patients studied. Local invasiveness
      (cavernous sinus penetration, optic chiasm compression or suprasellar extension)
      was observed in 18/31 patients (58,1%). Results Ki-67 was expressed in 77.4%,
      TOPO 2A in 87.1%, AIP in 83.8%, and VEGF in 87.1% of 31 cases of somatropinoma.
      Median values of Ki-67, TOPO 2A, AIP and cytoplasmic VEGF indices were 1.2%
      [IQR=2.2], 1.5% [IQR=1.6], 21.26% [IQR=20.1] and 20.4% [IQR=15.4], respectively.
      Ki-67, TOPO 2A, AIP and VEGF expression was not correlated with age nor with
      patient gender (p > 0.05). Only Ki-67 and TOPO 2A correlated with tumour size
      (for Ki-67: r=0.42, p=0.025; for TOPO 2A: r=0.53, p=0.003). Ki-67 and TOPO 2A
      levels were significantly higher in invasive compared to noninvasive
      somatropinomas (Ki67 mean values: 1.85+/-1.33% vs. 0.95+/-1.07%, p=0.024; TOPO 2A
      mean values: 2.19+/-1.63% vs. 1.45+/-1.23%, , p=0.011). Conclusions Ki-67, TOPO
      2A, AIP and VEGF were expressed in over 70% of all somatotropinomas. Only Ki-67
      and TOPO 2A expression correlated with tumour size and tumour invasiveness.

PMID- 29334119
TI  - Evaluation of Four Variants of the Thyroid Imaging Reporting and Data System
      (TIRADS) Classification in Patients with Multinodular Goitre - initial study.
AB  - Purpose The goal this study was to evaluate the utility of four variants of the
      Thyroid Imaging Reporting and Data System (TIRADS) in the differentiation of
      focal lesions in individuals with multinodular goiter. Materials and Methods The
      study was approved by the Local Bioethical Committee. Each patient gave informed
      consent before enrolment. A total of 163 nodules in 124 patients with
      multinodular goiter were evaluated by ultrasound. B-mode and PD imaging and
      strain elastography were performed. Archived images were evaluated via
      retrospective analysis using four different proposed TIRADS classifications
      Results Sensitivity and specificity of the Horvath, Park, Kwak, and Russ
      classifications were 0.625 and 0.769, 0.813 and 0.864, 0.938 and 0.667, and 0.875
      and 0.293, respectively. Positive and negative predictive values were 0.227 and
      0.95, 0.394 and 0.977, 0.234 and 0.99, and 0.119 and 0.956, respectively. Receive
      operating characteristic analysis suggests that the best differentiation
      potential was demonstrated by the Kwak classification with an area under the
      curve (AUC) of 0.896, followed by the Park (AUC = 0.872), Horvath (AUC = 0.774),
      and Russ (AUC = 0.729) classifications. Conclusion The TIRADS classification
      proposed by Kwak can be a useful tool in daily practice for the evaluation of
      thyroid cancer in individuals with multinodular goiter, particularly for
      selecting cases that require biopsy, which may improve and simplify clinical
      decision making. To adopt a definitive, comprehensive variant of the TIRADS
      classification with potential for universal, practical application, further
      prospective studies that include improvement of the lexicon and evaluation of the
      full spectrum of thyroid malignancy are warranted.

PMID- 29334120
TI  - Protein Phosphatase 1 dephosphorylates TDP-43 and suppresses its function in tau
      exon 10 inclusion.
AB  - Transactive response DNA-binding protein of 43 kDa (TDP-43) regulates RNA
      processing, including alternative splicing of tau exon 10. Pathological TDP-43 is
      hyperphosphorylated. However, how do the protein phosphatase(s) (PP) regulate TDP
      43 phosphorylation is unclear. Here, we found that both PP1 and PP2A were
      coimmunoprecipitated with TDP-43. Treatment with calyculin A, but not with
      okadaic acid, increased TDP-43 phosphorylation at Ser379, Ser403/404, and
      Ser409/410 in cultured cells. PP1alpha, PP1beta, and PP1gamma interacted with TDP
      43. Overexpression of PP1alpha and PP1gamma, but not PP1beta, suppressed TDP-43
      phosphorylation at Ser403/404 and Ser409/410 and TDP-43-induced tau exon 10
      inclusion. These findings suggest that PP1alpha and PP1gamma regulate TDP-43
      phosphorylation and its function in tau exon 10 inclusion mainly through its
      phosphorylation at Ser403/404 and Ser409/410.

PMID- 29334121
TI  - The multipotency-to-commitment transition in Caenorhabditis elegans-implications
      for reprogramming from cells to organs.
AB  - In animal embryos, cells transition from a multipotential state, with the
      capacity to adopt multiple fates, into an irreversible, committed state of
      differentiation. This multipotency-to-commitment transition (MCT) is evident from
      experiments in which cell fate is reprogrammed by transcription factors for cell
      type-specific differentiation, as has been observed extensively in Caenorhabditis
      elegans. Although factors that direct differentiation into each of the three germ
      layer types cannot generally reprogram cells after the MCT in this animal,
      transcription factors for endoderm development are able to do so in multiple
      differentiated cell types. In one case, these factors can redirect the
      development of an entire organ in the process of "transorganogenesis". Natural
      transdifferentiation also occurs in a small number of differentiated cells during
      normal C. elegans development. We review these reprogramming and
      transdifferentiation events, highlighting the cellular and developmental contexts
      in which they occur, and discuss common themes underlying direct cell lineage
      reprogramming. Although certain aspects may be unique to the model system,
      growing evidence suggests that some mechanisms are evolutionarily conserved and
      may shed light on cellular plasticity and disease in humans.

PMID- 29334122
TI  - Inhibition of HSP90alpha protects cultured neurons from oxygen-glucose
      deprivation induced necroptosis by decreasing RIP3 expression.
AB  - Heat shock protein 90alpha (HSP90alpha) maintains cell stabilization and
      regulates cell death, respectively. Recent studies have shown that HSP90alpha is
      involved in receptor interacting protein 3 (RIP3)-mediated necroptosis in HT29
      cells. It is known that oxygen and glucose deprivation (OGD) can induce
      necroptosis, which is regulated by RIP3 in neurons. However, it is still unclear
      whether HSP90alpha participates in the process of OGD-induced necroptosis in
      cultured neurons via the regulation of RIP3. Our study found that necroptosis
      occurs in primary cultured cortical neurons and PC-12 cells following exposure to
      OGD insult. Additionally, the expression of RIP3/p-RIP3, MLKL/p-MLKL, and the
      RIP1/RIP3 complex (necrosome) significantly increased following OGD, as measured
      through immunofluorescence (IF) staining, Western blotting (WB), and
      immunoprecipitation (IP) assay. Additionally, data from computer simulations and
      IP assays showed that HSP90alpha interacts with RIP3. In addition, HSP90alpha was
      overexpressed following OGD in cultured neurons, as measured through WB and IF
      staining. Inhibition of HSP90alpha in cultured neurons, using the specific
      inhibitor, geldanamycin (GA), and siRNA/shRNA of HSP90alpha, protected cultured
      neurons from necrosis. Our study showed that the inhibitor of HSP90alpha, GA,
      rescued cultured neurons not only by decreasing the expression of total
      RIP3/MLKL, but also by decreasing the expression of p-RIP3/p-MLKL and the
      RIP1/RIP3 necrosome. In this study, we reveal that inhibition of HSP90alpha
      protects primary cultured cortical neurons and PC-12 cells from OGD-induced
      necroptosis through the modulation of RIP3 expression.

PMID- 29334123
TI  - Cancer associated fibroblasts tailored tumor microenvironment of therapy
      resistance in gastrointestinal cancers.
AB  - Gastrointestinal cancers (GI), are a group of highly aggressive malignancies with
      heavy cancer-related mortalities. Even if continued development of therapy
      methods, therapy resistance has been a great obstruction for cancer treatment and
      thereby inevitably leads to depressed final mortality. Peritumoral cancer
      associated fibroblasts (CAFs), a versatile population assisting cancer cells to
      build a facilitated tumor microenvironment (TME), has been demonstrated exerting
      a promotion influence on cancer proliferation, migration, invasion, metastasis,
      and also therapy resistance. In this review, we provide an update progress in
      describing how CAFs mediate therapy resistance in GI by various means, meanwhile
      highlight the crosstalk between CAFs and cancer cells and present some vital
      signaling pathways activated by CAFs in this resistant process. Furthermore, we
      discuss the current advances in adopting novel drugs against CAFs and how the
      knowledge contributing to improved therapy efficacy in clinical practice. In sum,
      CAFs create a therapy-resistant TME in several aspects of GI progression,
      although some key problems about distinguishing CAFs subpopulations and
      controversial issues on pleiotropic CAFs in medication need to be solved for
      subsequent clinical application. Predictably, targeting therapy-resistant CAFs is
      a promising adjunctive treatment to benefit GI patients.

PMID- 29334124
TI  - Use of antiviral medications in drug reaction with eosinophilia and systemic
      symptoms (DRESS): A case of infantile DRESS.
AB  - A 3-month-old girl with Sturge-Weber syndrome presented with a morbilliform rash,
      eosinophilia, and fulminant liver failure to our tertiary pediatric hospital. She
      was diagnosed with drug reaction with eosinophilia and systemic symptoms
      complicated by viremia and evidence of viral hepatitis on liver biopsy. We
      discuss the role of viral reactivation in drug reaction with eosinophilia and
      systemic symptoms and the relevance of antiviral therapy in management.

PMID- 29334125
TI  - Determination of isoorientin levels in rat plasma after oral administration of
      Vaccinum bracteatum Thunb. methanol extract by high-performance liquid
      chromatography-tandem mass spectrometry.
AB  - A simple, sensitive and rapid liquid chromatography tandem mass spectrometry
      method (LC-MS/MS) was developed and validated for the determination of plasma
      isoorientin levels in rats. After simple protein precipitation using methanol,
      chromatographic analysis was performed using a Synergi 4MU polar-RP 80A column
      (150 * 2.0 mm, 4MUm) under isocratic conditions and a mobile phase consisting of
      0.1% formic acid in water and methanol (80:20, v/v) at a flow rate of 0.2 mL/min.
      In positive electrospray ionization mode, the protonated precursor and product
      ion transitions of isoorientin (m/z 449.0 -> 299.1) and of puerarin (the internal
      standard; m/z 417.1 -> 297.1) were acquired by multiple reaction monitoring.
      Calibration curves obtained for plasma showed good linearity over the
      concentration range 1-1000 ng/mL. The lower limit of quantification was 1 ng/mL.
      Intra- and inter-day precisions were within 8.8% relative standard deviation.
      Accuracies ranged from 92.1 and 109.7%. The isoorientin stability in rat plasma
      under typical handling/storage conditions also found to be acceptable. The
      developed method was applied successfully to a pharmacokinetic study of
      isoorientin orally administered as the methanol extract of Vaccinium bracteatum
      Thunb. or administered as pure isoorientin.

PMID- 29334126
TI  - Methylated PACs are more potent than their parent compounds: A study of aryl
      hydrocarbon receptor-mediated activity, degradability, and mixture interactions
      in the H4IIE-luc assay.
AB  - Twenty-six polycyclic aromatic compounds (PACs; including native polycyclic
      aromatic hydrocarbons [PAHs], hydroxylated PAHs, alkylated and oxygenated PAHs,
      and [alkylated] heterocyclic compounds) were investigated for their aryl
      hydrocarbon receptor (AhR)-mediated potencies in the H4IIE-luc bioassay.
      Potential degradabilities of PACs were investigated by use of various durations
      of exposure (24, 48, or 72 h), and various mixtures of PACs including PAHs,
      alkylated and oxygenated PAHs, and heterocyclic compounds were tested for their
      joint AhR-mediated potency. Additive behaviors of PACs in mixtures were studied
      by comparing observed mixture potencies with mixture potencies predicted by use
      of the concentration addition model. Methylated derivatives were more potent than
      their parent compounds in the H4IIE-luc assay. A time-dependent decrease in
      relative potency was observed for all AhR-active compounds, which may be
      indicative of in vitro biotransformation. Monomethylated compounds seemed to be
      more rapidly transformed than analogous unsubstituted compounds. In addition, the
      results showed that the predictive power of the concentration addition model
      increased with the number of compounds, suggesting additivity in multicomponent
      mixtures. Due to the greater potency of methylated derivatives and their
      ubiquitous occurrence, there is a need for further research on the toxicity and
      mixture behavior of these environmentally and toxicologically relevant compounds.
      Environ Toxicol Chem 2018;37:1409-1419. (c) 2018 SETAC.

PMID- 29334127
TI  - Non-enzymatic cross-linking of collagen type II fibrils is tuned via osmolality
      switch.
AB  - An important aspect in cartilage ageing is accumulation of advanced glycation end
      products (AGEs) after exposure to sugars. Advanced glycation results in cross
      links formation between the collagen fibrils in articular cartilage, hampering
      their flexibility and making cartilage more brittle. In the current study, we
      investigate whether collagen cross-linking after exposure to sugars depends on
      the stretching condition of the collagen fibrils. Healthy equine cartilage
      specimens were exposed to l-threose sugar and placed in hypo-, iso-, or hyper
      osmolal conditions that expanded or shrank the tissue and changed the 3D
      conformation of collagen fibrils. We applied micro-indentation tests, contrast
      enhanced micro-computed tomography, biochemical measurement of pentosidine cross
      links, and cartilage surface color analysis to assess the effects of advanced
      glycation cross-linking under these different conditions. Swelling of
      extracellular matrix due to hypo-osmolality made cartilage less susceptible to
      advanced glycation, namely, the increase in effective Young's modulus was
      approximately 80% lower in hypo-osmolality compared to hyper-osmolality and
      pentosidine content per collagen was 47% lower. These results indicate that
      healthy levels of glycosaminoglycans not only keep cartilage stiffness at
      appropriate levels by swelling and pre-stressed collagen fibrils, but also
      protect collagen fibrils from adverse effects of advanced glycation. These
      findings highlight the fact that collagen fibrils and therefore cartilage can be
      protected from further advanced glycation ("ageing") by maintaining the joint
      environment at sufficiently low osmolality. Understanding of mechanochemistry of
      collagen fibrils provided here might evoke potential ageing prohibiting
      strategies against cartilage deterioration. (c) 2018 The Authors. Journal of
      Orthopaedic Research Published by Wiley Periodicals, Inc. on behalf of
      Orthopaedic Research Society. J Orthop Res 36:1929-1936, 2018.

PMID- 29334128
TI  - Improved liver R2* mapping by pixel-wise curve fitting with adaptive neighborhood
      regularization.
AB  - PURPOSE: To improve liver R2* mapping by incorporating adaptive neighborhood
      regularization into pixel-wise curve fitting. METHODS: Magnetic resonance imaging
      R2* mapping remains challenging because of the serial images with low signal-to
      noise ratio. In this study, we proposed to exploit the neighboring pixels as
      regularization terms and adaptively determine the regularization parameters
      according to the interpixel signal similarity. The proposed algorithm, called the
      pixel-wise curve fitting with adaptive neighborhood regularization (PCANR), was
      compared with the conventional nonlinear least squares (NLS) and nonlocal means
      filter-based NLS algorithms on simulated, phantom, and in vivo data. RESULTS:
      Visually, the PCANR algorithm generates R2* maps with significantly reduced noise
      and well-preserved tiny structures. Quantitatively, the PCANR algorithm produces
      R2* maps with lower root mean square errors at varying R2* values and signal-to
      noise-ratio levels compared with the NLS and nonlocal means filter-based NLS
      algorithms. For the high R2* values under low signal-to-noise-ratio levels, the
      PCANR algorithm outperforms the NLS and nonlocal means filter-based NLS
      algorithms in the accuracy and precision, in terms of mean and standard deviation
      of R2* measurements in selected region of interests, respectively. CONCLUSIONS:
      The PCANR algorithm can reduce the effect of noise on liver R2* mapping, and the
      improved measurement precision will benefit the assessment of hepatic iron in
      clinical practice. Magn Reson Med 80:792-801, 2018. (c) 2018 International
      Society for Magnetic Resonance in Medicine.

PMID- 29334129
TI  - A mitochondrial-targeted antioxidant improves myofilament Ca2+ sensitivity during
      prolonged low frequency force depression at low PO2.
AB  - KEY POINTS: Skeletal muscle contractile activity is associated with an enhanced
      reactive oxygen species (ROS) generation. At very low PO2, ROS generation by
      mitochondria can be elevated in intact cells. An elevated intracellular oxidant
      activity may affect muscle force development and recovery from fatigue. We
      treated intact single muscle fibres with a mitochondrial antioxidant and
      stimulated the fibres to contract at a low extracellular PO2 that is similar to
      the intracellular PO2 that is observed during moderate to intense exercise in
      vivo. The mitochondrial antioxidant prevented a sustained decrease in the
      myofibrillar Ca2+ sensitivity and improved muscle submaximal force development
      after fatigue at low extracellular PO2. ABSTRACT: Skeletal muscle can develop a
      prolonged low frequency-stimulation force depression (PLFFD) following fatigue
      inducing contractions. Increased levels of reactive oxygen species (ROS) have
      been implicated in the development of PLFFD. During exercise the skeletal muscle
      intracellular PO2 decreases to relatively low levels, and can be further
      decreased when there is an impairment in O2 diffusion or availability, such as in
      certain chronic diseases and during exercise at high altitude. Since ROS
      generation by mitochondria is elevated at very low PO2 in cells, we tested the
      hypothesis that treatment of muscle fibres with a mitochondrial-targeted
      antioxidant at a very low, near hypoxic, PO2 can attenuate PLFFD. We treated
      intact single fibres from mice with the mitochondrial-specific antioxidant SS31,
      and measured force development and intracellular [Ca2+ ] 30 min after fatigue at
      an extracellular PO2 of ~5 Torr. After 30 min following the end of the fatiguing
      contractions, fibres treated with SS31 showed significantly less impairment in
      force development compared to untreated fibres at submaximal frequencies of
      stimulation. The cytosolic peak [Ca2+ ] transients (peak [Ca2+ ]c ) were equally
      decreased in both groups compared to pre-fatigue values. The combined force and
      peak [Ca2+ ]c data demonstrated that myofibrillar Ca2+ sensitivity was diminished
      in the untreated fibres 30 min after fatigue compared to pre-fatigue values, but
      Ca2+ sensitivity was unaltered in the SS31 treated fibres. These results
      demonstrate that at a very low PO2, treatment of skeletal muscle fibres with a
      mitochondrial antioxidant prevents a decrease in the myofibrillar Ca2+
      sensitivity, which alleviates the fatigue induced PLFFD.

PMID- 29334130
TI  - Radiofrequency ablation combined with multiple biliary metal stent placement
      using short-type single-balloon endoscope in patients with surgically altered
      anatomy.

PMID- 29334131
TI  - A bayesian method for accelerated magnetic resonance elastography of the liver.
AB  - PURPOSE: Magnetic resonance elastography is a noninvasive tool for quantifying
      soft tissue stiffness. Magnetic resonance elastography has been adopted as a
      clinical method for staging liver fibrosis. However, the application of liver
      magnetic resonance elastography requires multiple lengthy breath-holds. We
      propose a new data acquisition and processing method to reduce magnetic resonance
      elastography scan time. METHODS: A Bayesian image reconstruction method that uses
      transform sparsity and magnitude consistency across different phase offsets to
      recover images from highly undersampled data is proposed. The method is validated
      using retrospectively down-sampled phantom data and prospectively down-sampled in
      vivo data (N = 86). RESULTS: The proposed technique allows accurate
      quantification of mean liver stiffness up to an acceleration factor of R = 6,
      enabling acquisition of a slice in 4.3 s. Bland-Altman analysis indicates that
      the proposed technique (R = 6) has a bias of -0.04 kPa and limits of agreement of
      -0.36 to + 0.28 kPa when compared with traditional generalized autocalibrating
      partial parallel acquisition reconstruction (R = 1.4). CONCLUSION: By exploiting
      transform sparsity and magnitude consistency, accurate quantification of mean
      stiffness in the liver can be obtained at an acceleration rate of up to R = 6.
      This potentially enables the collection of three to four liver slices, as per
      clinical protocol, within a single breath-hold. Magn Reson Med 80:1178-1188,
      2018. (c) 2018 International Society for Magnetic Resonance in Medicine.

PMID- 29334132
TI  - Oxybutynin 3% gel for the treatment of primary focal hyperhidrosis in adolescents
      and young adults.
AB  - BACKGROUND/OBJECTIVES: There are no reliably effective, well-tolerated topical
      agents for the treatment of hyperhidrosis. We sought to evaluate the efficacy and
      tolerability of oxybutynin 3% gel in adolescents and young adults with primary
      focal hyperhidrosis. METHODS: Patients with severe axillary hyperhidrosis were
      treated with topical oxybutynin 3% gel for 4 weeks. Response to treatment was
      assessed by calculating change in Hyperhidrosis Disease Severity Score from
      baseline to weeks 1 and 4. Change in health-related quality of life was assessed
      using the Children's Dermatology Life Quality Index or the Dermatology Life
      Quality Index. Adverse effects were evaluated using patient diaries, investigator
      global review, and physical examination. RESULTS: Of 10 patients aged 13-24
      enrolled, seven completed the study. Of those who completed the study, four
      (57.1%) reported reduction in axillary Hyperhidrosis Disease Severity Score at
      week 1 and all seven (100%) at week 4. Six patients (85.7%) reported reduction in
      Children's Dermatology Life Quality Index or Dermatology Life Quality Index
      score. Anticholinergic adverse effects were infrequent. The majority of treatment
      related adverse events were mild to moderate in severity. One patient experienced
      a severe adverse event. CONCLUSION: Oxybutynin 3% gel reduced hyperhidrosis
      severity and improved health-related quality of life in this small pilot study.
      Safety and efficacy should be further evaluated in a large, prospective, placebo
      controlled study.

PMID- 29334133
TI  - Hierarchical Porous Nanosheets Constructed by Graphene-Coated, Interconnected
      TiO2 Nanoparticles for Ultrafast Sodium Storage.
AB  - Sodium-ion batteries (SIBs) are considered promising next-generation energy
      storage devices. However, a lack of appropriate high-performance anode materials
      has prevented further improvements. Here, a hierarchical porous hybrid nanosheet
      composed of interconnected uniform TiO2 nanoparticles and nitrogen-doped graphene
      layer networks (TiO2 @NFG HPHNSs) that are synthesized using dual-functional C3
      N4 nanosheets as both the self-sacrificing template and hybrid carbon source is
      reported. These HPHNSs deliver high reversible capacities of 146 mA h g-1 at 5 C
      for 8000 cycles, 129 mA h g-1 at 10 C for 20 000 cycles, and 116 mA h g-1 at 20 C
      for 10 000 cycles, as well as an ultrahigh rate capability up to 60 C with a
      capacity of 101 mA h g-1 . These results demonstrate the longest cyclabilities
      and best rate capability ever reported for TiO2 -based anode materials for SIBs.
      The unprecedented sodium storage performance of the TiO2 @NFG HPHNSs is due to
      their unique composition and hierarchical porous 2D structure.

PMID- 29334134
TI  - A comprehensive next-generation sequencing assay for the diagnosis of
      epidermolysis bullosa.
AB  - BACKGROUND: Historically, diagnosis of epidermolysis bullosa has required skin
      biopsies for electron microscopy, direct immunofluorescence to determine which
      gene(s) to choose for genetic testing, or both. METHODS: To avoid these invasive
      tests, we developed a high-throughput next-generation sequencing (NGS)-based
      diagnostic assay called EBSEQ that allows simultaneous detection of mutations in
      21 genes with known roles in epidermolysis bullosa pathogenicity. Mutations are
      confirmed with traditional Sanger sequencing. RESULTS: We present our EBSEQ assay
      and preliminary studies on the first 43 subjects tested. We identified 11 cases
      of epidermolysis bullosa simplex, five cases of junctional epidermolysis bullosa,
      11 cases of dominant dystrophic epidermolysis bullosa, 15 cases of recessive
      dystrophic epidermolysis bullosa, and one case that remains without diagnosis. We
      also found an additional 52 variants of uncertain clinical significance in 17 of
      the 21 epidermolysis bullosa-associated genes tested. Three of the variants of
      uncertain clinical significance were also found in three other patients, for a
      total of 49 unique variants of uncertain clinical significance. We found the
      clinical sensitivity of the assay to be 75% to 98% and the analytical sensitivity
      to be 99% in identifying base substitutions and small deletions and duplications.
      Turnaround time was 3 to 6 weeks. CONCLUSIONS: EBSEQ is a sensitive, relatively
      rapid, minimally invasive, comprehensive genetic assay for the diagnosis of
      epidermolysis bullosa.

PMID- 29334135
TI  - Liquid Letters.
AB  - Using the interfacial jamming of cellulose nanocrystal (CNC) surfactants, a new
      concept, termed all-liquid molding, is introduced to produce all-liquid objects
      that retain the shape and details of the mold with high fidelity, yet remain all
      liquid and are responsive to external stimuli. This simple process, where the
      viscosity of the CNC dispersion can range from that of water to a crosslinked
      gel, opens tremendous opportunities for encapsulation, delivery systems, and
      unique microfluidic devices. The process described is generally applicable to any
      functionalized nanoparticles dispersed in one liquid and polymer ligands having
      complementary functionality dissolved in a second immiscible liquid. Such
      sculpted liquids retain all the characteristics of the liquids but retain shape
      indefinitely, very much like a solid, and provide a new platform for next
      generation soft materials.

PMID- 29334136
TI  - Bayesian network meta-analysis: Efficacy of air insufflation, CO2 insufflation,
      water exchange, and water immersion in colonoscopy.
AB  - BACKGROUND AND AIM: Colonoscopy is an excellent screening tool for colorectal
      cancer. There are four colonoscopy techniques: air insufflation, CO2
      insufflation, water exchange, and water immersion. Some studies reported that the
      latter three methods are better than the criterion standard (air insufflation),
      whereas some studies did not. In order to evaluate the efficacy of the four
      colonoscopy techniques, a network meta-analysis was carried out. METHODS: We
      searched randomized controlled trials (RCT) published up to September 2017 from
      PubMed, Embase, Cochrane library, and Web of Science. Studies referencing the
      comparison between at least two of air insufflation, CO2 insufflation, water
      exchange, and water immersion were selected. Primary outcomes included pain score
      during insertion, polyp detection rate, and adenoma detection rate, and secondary
      outcomes included cecal intubation time and cecal intubation rate. Mean
      differences or odds ratios and their corresponding 95% credible intervals were
      pooled with Bayesian modeling. RESULTS: Forty RCT with 13 734 patients were
      included in this network meta-analysis. Our analysis showed that air insufflation
      had the highest pain score (surface under the cumulative ranking curve [SUCRA]:
      98.8%) and the lowest detection rate of adenoma (SUCRA: 21.3%) and polyp (SUCRA:
      16.8%). Water exchange had the lowest pain score (SUCRA: 1.1%) and highest
      detection rate of adenoma (SUCRA: 96.0%) and polyp (SUCRA: 98.9%), although it
      led to the longest cecal intubation time (SUCRA: 86.9%). CONCLUSIONS: Air
      insufflation might be the most unsatisfactory colonoscopy. Meanwhile, water
      exchange might be the most efficient colonoscopy.

PMID- 29334137
TI  - Calcium phosphate precipitation in experimental gaps between fluoride-containing
      fast-setting calcium silicate cement and dentin.
AB  - A novel fast-setting calcium silicate cement containing fluoride (novel-CSC) has
      been developed for applications in tooth crowns. The aim of this study was to
      assess the ability of the novel-CSC to close the experimental gaps at the dentin
      cement interface. The novel-CSC was tested against Vitrebond and GC Fuji II LC.
      Experimental gaps of 50 or 300 MUm width were created between the materials and
      dentin. Specimens with the 300-MUm-wide gap were immersed in phosphate-buffered
      saline and the closed gap area was measured during 96 h. All specimens with 50 or
      300 MUm gap width were analyzed by scanning electron microscopy equipped with
      energy dispersive X-ray spectroscopy (SEM/EDX) to assess the morphology and
      chemical composition of the precipitates after 96 h immersion in phosphate
      buffered saline. High-resolution micro-computed tomography (MUCT) was used to
      evaluate the integrity and continuity of the precipitiates after 96 h and 180 d.
      In all novel-CSC samples, precipitates closed the gap area completely after 96 h.
      The SEM/EDX revealed that the globular precipitates closing the gap area were
      mainly composed of calcium and phosphorus. After 180 d, MUCT indicated thicker
      precipitates compared with initial precipitates only in the novel-CSC group,
      whereas no precipitates were observed in resin-modified glass ionomers. Novel-CSC
      promoted continuous precipitation of calcium phosphate, including apatite, and
      closed the experimental gaps.

PMID- 29334138
TI  - Moving knife tip on the thoracic aorta: High-risk submucosal tunneling endoscopic
      resection procedure for a puzzling submucosal mass in the esophagus.

PMID- 29334139
TI  - Interleaved susceptibility-weighted and FLAIR MRI for imaging lesion-penetrating
      veins in multiple sclerosis.
AB  - PURPOSE: To simultaneously image brain lesions and veins in multiple sclerosis.
      METHODS: An interleaved sequence was developed to simultaneously acquire 3
      dimensional T2*-weighted (or susceptibility-weighted (SW)) and fluid-attenuated
      inversion recovery (FLAIR) images on a 3T MRI system. The pulse sequence
      parameters were calculated to minimize signal perturbation from steady state
      while maintaining acceptable image contrast and scan time. Fifteen multiple
      sclerosis patients were enrolled in this prospective study and underwent a
      standard multiple sclerosis imaging protocol. In addition, SW and FLAIR images
      were acquired separately and also in an interleaved manner. The SW and FLAIR
      images were combined into one image to visualize lesions and penetrating veins.
      The contrast ratios between white matter lesions and penetrating veins were
      compared between the interleaved sequence and the individual noninterleaved
      acquisitions. RESULTS: Interleaved scanning of the FLAIR and the SW pulse
      sequences was achieved, producing aligned images, and with similar image contrast
      as in the noninterleaved images. A total of 1076 lesions were identified in all
      patients on the combined SW-FLAIR image, of which 968 lesions (90%) had visible
      penetrating veins. Lesion-to-vein contrast ratio was 32.7 +/- 17.9 (mean +/-
      standard deviation) for the interleaved sequence compared with 28.1 +/- 13.7
      using the separate acquisitions (P < 0.001). CONCLUSION: The feasibility of
      interleaved acquisition of SW and FLAIR images was demonstrated. This sequence
      provides self-registered images and facilitates the visualization of veins in
      brain lesions. Magn Reson Med 80:1132-1137, 2018. (c) 2018 International Society
      for Magnetic Resonance in Medicine.

PMID- 29334140
TI  - Slit Tubes for Semisoft Pneumatic Actuators.
AB  - This article describes a new principle for designing soft or 'semisoft' pneumatic
      actuators: SLiT (for SLit-in-Tube) actuators. Inflating an elastomeric balloon,
      when enclosed by an external shell (a material with higher Young's modulus)
      containing slits of different directions and lengths, produces a variety of
      motions, including bending, twisting, contraction, and elongation. The requisite
      pressure for actuation depends on the length of the slits, and this dependence
      allows sequential actuation by controlling the applied pressure. Different
      actuators can also be controlled using external "sliders" that act as
      reprogrammable "on-off" switches. A pneumatic arm and a walker constructed from
      SLiT actuators demonstrate their ease of fabrication and the range of motions
      they can achieve.

PMID- 29334141
TI  - Characterization of macromolecular baseline of human brain using metabolite
      cycled semi-LASER at 9.4T.
AB  - PURPOSE: Macromolecular resonances (MM) arise mainly from cytosolic proteins and
      overlap with metabolites, influencing metabolite quantification. Macromolecules
      can serve as valuable biomarkers for diseases and pathologies. The objectives of
      this study were to characterize MM at 9.4T in the human brain (occipital and left
      parietal lobe) and to describe the RF coil setup used for MM acquisition in the
      two regions. METHODS: An adiabatic inversion pulse was optimised for metabolite
      nulling at 9.4T using double inversion recovery and was combined for the first
      time with metabolite cycled (MC) semi-LASER and appropriate coil configuration.
      MM spectra (seven volunteers) from two brain locations were averaged and smoothed
      creating MM templates, which were then parametrized using simulated Voigt-shaped
      lines within LCModel. Quantification was performed on individual data sets,
      including corrections for different tissue composition and the T1 and T2
      relaxation of water. RESULTS: Our coil configuration method resulted in efficient
      B1+ (>30 T/?kW) for both brain regions. The 15 MM components were detected and
      quantified in MM baselines of the two brain areas. No significant differences in
      concentration levels of MM between different regions were found. Two new MM peaks
      were reported (M7 & M8). CONCLUSION: Double inversion, which was combined with MC
      semi-LASER, enabled the acquisition of high spectral resolution MM spectra for
      both brain regions at 9.4T. The 15 MM components were detected and quantified.
      Two new MM peaks were reported for the first time (M7 & M8) and preliminarily
      assigned to beta-methylene protons of aspartyl-groups. Magn Reson Med 80:462-473,
      2018. (c) 2018 International Society for Magnetic Resonance in Medicine.

PMID- 29334142
TI  - Severe ectropion in lamellar ichthyosis managed medically with oral acitretin.
AB  - Congenital ectropion is commonly associated with lamellar ichthyosis. Severe
      eyelid ectropion may cause corneal exposure, keratopathy, and permanent corneal
      scarring. We report a neonate with severe, bilateral, congenital ectropion and
      eclabium managed using oral retinoids. Both corneas were protected with topical
      antibiotics and lubricating eyedrops and eye ointments. At 12-month follow-up,
      the child was doing well, with no ectropion or corneal opacity.

PMID- 29334143
TI  - Childhood alopecia areata-Data from the National Alopecia Areata Registry.
AB  - BACKGROUND/OBJECTIVES: Alopecia areata may occur at any age and is the third-most
      common dermatosis in children. The objective of this study was to investigate the
      clinical and epidemiologic features of children and adolescents with alopecia
      areata based on the data of the National Alopecia Areata registry on children and
      adolescents. METHODS: Two thousand two hundred eighteen children and adolescents
      with alopecia areata self-enrolled in the National Alopecia Areata Registry and
      completed a web-based, self-administered, short-intake screening questionnaire
      (first tier). In the second tier, 643 patients participated in a clinical
      examination and completed a long-form questionnaire. RESULTS: Mean age of onset
      was 5.9 +/- 4.1 years. With a female to male ratio of 1.5:1, alopecia areata was
      more prevalent in girls, but boys were significantly more likely to have a severe
      type (P = .009). One-fourth of all children had a positive family history, with
      8% having more than three affected relatives. The disease most commonly
      associated with alopecia areata was atopic dermatitis (32.7%). CONCLUSION:
      Childhood alopecia areata is more prevalent in girls than in boys, but boys have
      more extensive alopecia areata. Despite the low prevalence, congenital alopecia
      areata is an important differential diagnosis for neonatal hair loss. Alopecia
      areata runs in families, suggesting an underlying genetic background. One-quarter
      of the children reported at least one affected first-degree relative; 8% had more
      than three affected relatives.

PMID- 29334144
TI  - Acute gastrointestinal bleeding from appendiceal diverticulitis diagnosed
      preoperatively by combined short-interval computed tomography and colonoscopy: A
      case report.

PMID- 29334145
TI  - Colloidal Cobalt Phosphide Nanocrystals as Trifunctional Electrocatalysts for
      Overall Water Splitting Powered by a Zinc-Air Battery.
AB  - Highly efficient and stable electrocatalysts, particularly those that are capable
      of multifunctionality in the same electrolyte, are in high demand for the
      hydrogen evolution reaction (HER), oxygen evolution reaction (OER), and oxygen
      reduction reaction (ORR). In this work, highly monodisperse CoP and Co2 P
      nanocrystals (NCs) are synthesized using a robust solution-phase method. The
      highly exposed (211) crystal plane and abundant surface phosphide atoms make the
      CoP NCs efficient catalysts toward ORR and HER, while metal-rich Co2 P NCs show
      higher OER performance owing to easier formation of plentiful Co2 P@COOH
      heterojunctions. Density functional theory calculation results indicate that the
      desorption of OH* from cobalt sites is the rate-limiting step for both CoP and
      Co2 P in ORR and that the high content of phosphide can lower the reaction
      barrier. A water electrolyzer constructed with a CoP NC cathode and a Co2 P NC
      anode can achieve a current density of 10 mA cm-2 at 1.56 V, comparable even to
      the noble metal-based Pt/C and RuO2 /C pair. Furthermore, the CoP NCs are
      employed as an air cathode in a primary zinc-air battery, exhibiting a high power
      density of 62 mW cm-2 and good stability.

PMID- 29334146
TI  - Self-Assembled Ag-MXA Superclusters with Structure-Dependent Mechanical
      Properties.
AB  - The low elastic modulus and time-consuming formation process represent the major
      challenges that impede the penetration of nanoparticle superstructures into daily
      life applications. As observed in the molecular or atomic crystals, more
      effective interactions between adjacent nanoparticles would introduce beneficial
      features to assemblies enabling optimized mechanical properties. Here, a
      straightforward synthetic strategy is showed that allows fast and scalable
      fabrication of 2D Ag-mercaptoalkyl acid superclusters of either hexagonal or
      lamellar topology. Remarkably, these ordered superstructures exhibit a structure
      dependent elastic modulus which is subject to the tether length of straight-chain
      mercaptoalkyl acids or the ratio between silver and tether molecules. These
      superclusters are plastic and moldable against arbitrarily shaped masters of
      macroscopic dimensions, thereby opening a wealth of possibilities to develop more
      nanocrystals with practically useful nanoscopic properties.

PMID- 29334147
TI  - Uniform Lithium Nucleation/Growth Induced by Lightweight Nitrogen-Doped Graphitic
      Carbon Foams for High-Performance Lithium Metal Anodes.
AB  - The lithium metal anode has attracted soaring attention as an ideal battery
      anode. Unfortunately, nonuniform Li nucleation results in uncontrollable growth
      of dendritic Li, which incurs serious safety issues and poor electrochemical
      performance, hindering its practical applications. Herein, this study shows that
      uniform Li nucleation/growth can be induced by an ultralight 3D current collector
      consisting of in situ nitrogen-doped graphitic carbon foams (NGCFs) to realize
      suppressing dendritic Li growth at the nucleating stage. The N-containing
      functional groups guide homogenous growth of Li nucleus nanoparticles and the
      initial Li nucleus seed layer regulates the following well-distributed Li growth.
      Benefiting from such favorable Li growth behavior, superior electrochemical
      performance can be achieved as evidenced by the high Coulombic efficiency (~99.6%
      for 300 cycles), large capacity (10 mA h cm-2 , 3140 mA h g-1NGCF-Li ), and
      ultralong lifespan (>1200 h) together with low overpotential (<25 mV at 3 mA cm-2
      ); even under a high current density up to 10 mA cm-2 , it still displays low
      overpotential of 62 mV.

PMID- 29334149
TI  - Evidence based practice readiness: A concept analysis.
AB  - AIM: To analyse and define the concept "evidence based practice readiness" in
      nurses. BACKGROUND: Evidence based practice readiness is a term commonly used in
      health literature, but without a clear understanding of what readiness means.
      Concept analysis is needed to define the meaning of evidence based practice
      readiness. METHOD: A concept analysis was conducted using Walker and Avant's
      method to clarify the defining attributes of evidence based practice readiness as
      well as antecedents and consequences. A Boolean search of PubMed and Cumulative
      Index for Nursing and Allied Health Literature was conducted and limited to those
      published after the year 2000. Eleven articles met the inclusion criteria for
      this analysis. RESULTS: Evidence based practice readiness incorporates personal
      and organisational readiness. Antecedents include the ability to recognize the
      need for evidence based practice, ability to access and interpret evidence based
      practice, and a supportive environment. CONCLUSION: The concept analysis
      demonstrates the complexity of the concept and its implications for nursing
      practice. The four pillars of evidence based practice readiness: nursing,
      training, equipping and leadership support are necessary to achieve evidence
      based practice readiness. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse managers are
      in the position to address all elements of evidence based practice readiness.
      Creating an environment that fosters evidence based practice can improve patient
      outcomes, decreased health care cost, increase nurses' job satisfaction and
      decrease nursing turnover.

PMID- 29334148
TI  - Self-Powered Si/CdS Flexible Photodetector with Broadband Response from 325 to
      1550 nm Based on Pyro-phototronic Effect: An Approach for Photosensing below
      Bandgap Energy.
AB  - Cadmium sulfide (CdS) has received widespread attention as the building block of
      optoelectronic devices due to its extraordinary optoelectronic properties, low
      work function, and excellent thermal and chemical stability. Here, a self-powered
      flexible photodetector (PD) based on p-Si/n-CdS nanowires heterostructure is
      fabricated. By introducing the pyro-phototronic effect derived from wurtzite
      structured CdS, the self-powered PD shows a broadband response range, even beyond
      the bandgap limitation, from UV (325 nm) to near infrared (1550 nm) under zero
      bias with fast response speed. The light-induced pyroelectric potential is
      utilized to modulate the optoelectronic processes and thus improve the
      photoresponse performance. Lasers with different wavelengths have different
      effects on the self-powered PDs and corresponding working mechanisms are
      carefully investigated. Upon 325 nm laser illumination, the rise time and fall
      time of the self-powered PD are 245 and 277 us, respectively, which are faster
      than those of most previously reported CdS-based nanostructure PDs. Meanwhile,
      the photoresponsivity R and specific detectivity D* regarding to the relative
      peak-to-peak current are both enhanced by 67.8 times, compared with those only
      based on the photovoltaic effect-induced photocurrent. The self-powered flexible
      PD with fast speed, stable, and broadband response is expected to have extensive
      applications in various environments.

PMID- 29334150
TI  - A General Method for the Chemical Synthesis of Large-Scale, Seamless Transition
      Metal Dichalcogenide Electronics.
AB  - The capability to directly build atomically thin transition metal dichalcogenide
      (TMD) devices by chemical synthesis offers important opportunities to achieve
      large-scale electronics and optoelectronics with seamless interfaces. Here, a
      general approach for the chemical synthesis of a variety of TMD (e.g., MoS2 , WS2
      , and MoSe2 ) device arrays over large areas is reported. During chemical vapor
      deposition, semiconducting TMD channels and metallic TMD/carbon nanotube (CNT)
      hybrid electrodes are simultaneously formed on CNT-patterned substrate, and then
      coalesce into seamless devices. Chemically synthesized TMD devices exhibit
      attractive electrical and mechanical properties. It is demonstrated that
      chemically synthesized MoS2 -MoS2 /CNT devices have Ohmic contacts between MoS2
      /CNT hybrid electrodes and MoS2 channels. In addition, MoS2 -MoS2 /CNT devices
      show greatly enhanced mechanical stability and photoresponsivity compared with
      conventional gold-contacted devices, which makes them suitable for flexible
      optoelectronics. Accordingly, a highly flexible pixel array based on chemically
      synthesized MoS2 -MoS2 /CNT photodetectors is applied for image sensing.

PMID- 29334151
TI  - Fused Tris(thienothiophene)-Based Electron Acceptor with Strong Near-Infrared
      Absorption for High-Performance As-Cast Solar Cells.
AB  - A fused tris(thienothiophene) (3TT) building block is designed and synthesized
      with strong electron-donating and molecular packing properties, where three
      thienothiophene units are condensed with two cyclopentadienyl rings. Based on
      3TT, a fused octacylic electron acceptor (FOIC) is designed and synthesized,
      using strong electron-withdrawing 2-(5/6-fluoro-3-oxo-2,3-dihydro-1H-inden-1
      ylidene)-malononitrile as end groups. FOIC exhibits absorption in 600-950 nm
      region peaked at 836 nm with extinction coefficient of up to 2 * 105 m-1 cm-1 ,
      low bandgap of 1.32 eV, and high electron mobility of 1.2 * 10-3 cm2 V-1 s-1 .
      Compared with its counterpart ITIC3 based on indacenothienothiophene core, FOIC
      exhibits significantly upshifted highest occupied molecular orbital level,
      slightly downshifted lowest unoccupied molecular orbital level, significantly
      redshifted absorption, and higher mobility. The as-cast organic solar cells
      (OSCs) based on blends of PTB7-Th donor and FOIC acceptor without additional
      treatments exhibit power conversion efficiencies (PCEs) as high as 12.0%, which
      is much higher than that of PTB7-Th: ITIC3 (8.09%). The as-cast semitransparent
      OSCs based on the same blends show PCEs of up to 10.3% with an average visible
      transmittance of 37.4%.

PMID- 29334152
TI  - Dynamic Coordination of Eu-Iminodiacetate to Control Fluorochromic Response of
      Polymer Hydrogels to Multistimuli.
AB  - New fluorochromic materials that reversibly change their emission properties in
      response to their environment are of interest for the development of sensors and
      light-emitting materials. A new design of Eu-containing polymer hydrogels showing
      fast self-healing and tunable fluorochromic properties in response to five
      different stimuli, including pH, temperature, metal ions, sonication, and force,
      is reported. The polymer hydrogels are fabricated using Eu-iminodiacetate (IDA)
      coordination in a hydrophilic poly(N,N-dimethylacrylamide) matrix. Dynamic metal
      ligand coordination allows reversible formation and disruption of hydrogel
      networks under various stimuli which makes hydrogels self-healable and
      injectable. Such hydrogels show interesting switchable ON/OFF luminescence along
      with the sol-gel transition through the reversible formation and dissociation of
      Eu-IDA complexes upon various stimuli. It is demonstrated that Eu-containing
      hydrogels display fast and reversible mechanochromic response as well in
      hydrogels having interpenetrating polymer network. Those multistimuli responsive
      fluorochromic hydrogels illustrate a new pathway to make smart optical materials,
      particularly for biological sensors where multistimuli response is required.

PMID- 29334153
TI  - Heterobimetallic Complexes for Theranostic Applications.
AB  - The design of more efficient anticancer drugs requires a deeper understanding of
      their biodistribution and mechanism of action. Cell imaging agents could help to
      gain insight into biological processes and, consequently, the best strategy for
      attaining suitable scaffolds in which both biological and imaging properties are
      maximized. A new concept arises in this field that is the combination of two
      metal fragments as collaborative partners to provide the precise emissive
      properties to visualize the cell as well as the optimum cytotoxic activity to
      build more potent and selective chemotherapeutic agents.

PMID- 29334154
TI  - Nano Titanium Monoxide Crystals and Unusual Superconductivity at 11 K.
AB  - Nano TiO2 is investigated intensely due to extraordinary photoelectric
      performances in photocatalysis, new-type solar cells, etc., but only very few
      synthesis and physical properties have been reported on nanostructured TiO or
      other low valent titanium-containing oxides. Here, a core-shell nanoparticle made
      of TiO core covered with a ~5 nm shell of amorphous TiO1+x is newly constructed
      via a controllable reduction method to synthesize nano TiO core and subsequent
      soft oxidation to form the shell (TiO1+x ). The physical properties measurements
      of electrical transport and magnetism indicate these TiO@TiO1+x nanocrystals are
      a type-II superconductor of a recorded Tconset = 11 K in the binary Ti-O system.
      This unusual superconductivity could be attributed to the interfacial effect due
      to the nearly linear gradient of O/Ti ratio across the outer amorphous layer.
      This novel synthetic method and enhanced superconductivity could open up
      possibilities in interface superconductivity of nanostructured composites with
      well-controlled interfaces.

PMID- 29334155
TI  - Response selection codes in neurophysiological data predict conjoint effects of
      controlled and automatic processes during response inhibition.
AB  - The inhibition of prepotent responses is a requirement for goal-directed behavior
      and several factors determine corresponding successful response inhibition
      processes. One factor relates to the degree of automaticity of pre-potent
      response tendencies and another factor relates to the degree of cognitive control
      that is exerted during response inhibition. However, both factors can conjointly
      modulate inhibitory control. Cognitive theoretical concepts suggest that codings
      of stimulus-response translations may underlie such conjoint effects. Yet, it is
      unclear in how far such specific codes, as assumed in cognitive psychological
      concepts, are evident in neurophysiological processes and whether there are
      specific functional neuroanatomical structures associated with the processing of
      such codes. Applying a temporal decomposition method of EEG data in combination
      with source localization methods we show that there are different, intermingled
      codes (i.e., "stimulus codes" and "response selection codes") at the
      neurophysiological level during conjoint effects of "automatic" and "controlled"
      processes in response inhibition. Importantly, only "response selection codes"
      predict behavioral performance, and are subject to conjoint modulations by
      "automatic" and "controlled" processes. These modulations are associated with
      inferior and superior parietal areas (BA40/BA7), possibly reflecting an updating
      of internal representations when information is complex and probably difficult to
      categorize, but essential for behavioral control. Codes proposed by cognitive,
      psychological concepts seem to have a neurophysiological analogue that fits into
      current views on functions of inferior and superior parietal regions.

PMID- 29334156
TI  - The retinal ganglion cell layer predicts normal-appearing white matter tract
      integrity in multiple sclerosis: A combined diffusion tensor imaging and optical
      coherence tomography approach.
AB  - We investigated the relationship between retinal layers and normal-appearing
      white matter (WM) integrity in the brain of patients with relapsing-remitting
      multiple sclerosis (MS), using a combined diffusion tensor imaging and high
      resolution optical coherence tomography approach. Fifty patients and 62 controls
      were recruited. The patients were divided into two groups according to presence
      (n = 18) or absence (n = 32) of optic neuritis. Diffusion tensor data were
      analyzed with a voxel-wise whole brain analysis of diffusion metrics in WM with
      tract-based spatial statistics. Thickness measurements were obtained for each
      individual retinal layer. Partial correlation and multivariate regression
      analyses were performed, assessing the association between individual retinal
      layers and diffusion metrics across all groups. Region-based analysis was
      performed, by focusing on tracts associated with the visual system. Receiver
      operating characteristic (ROC) curves were computed to compare the biomarker
      potential for the diagnosis of MS, using the thickness of each retinal layer and
      diffusion metrics. In patients without optic neuritis, both ganglion cell layer
      (GCL) and inner plexiform layer thickness correlated with the diffusion metrics
      within and outside the visual system. GCL thickness was a significant predictor
      of diffusion metrics in the whole WM skeleton, unlike other layers. No
      association was observed for either controls or patients with a history of optic
      neuritis. ROC analysis showed that the biomarker potential for the diagnosis of
      MS based on the GCL was high when compared to other layers. We conclude that GCL
      integrity is a predictor of whole-brain WM disruption in MS patients without
      optic neuritis.

PMID- 29334157
TI  - Elevated sympathetic vasomotor outflow in response to increased inspiratory
      muscle activity during exercise is less in young women compared with men.
AB  - NEW FINDINGS: What is the central question of this study? Premenopausal women
      have an attenuated inspiratory muscle metaboreflex-induced increase in arterial
      blood pressure compared with men. It is unclear whether sympathetic vasomotor
      outflow during dynamic exercise with increased inspiratory muscle activation is
      less in young women than in men. What is the main finding and its importance? The
      magnitude of increased sympathetic vasomotor outflow during leg cycling with
      inspiratory resistance was smaller in women than in men. Less sympathetic
      vasomotor outflow with inspiratory muscle metaboreflex activation could be one of
      the mechanisms for the attenuated inspiratory muscle-induced metaboreflex during
      exercise in young women. ABSTRACT: We compared changes in muscle sympathetic
      nerve activity (MSNA) and cardiovascular variables during leg cycle exercise with
      increased inspiratory muscle resistance in men and women. We hypothesized that
      sympathetic vasomotor outflow during exercise with increased inspiratory
      resistance would be attenuated in young women compared with age-matched men.
      Eight women and seven men completed the study. The subjects performed two 10 min
      exercise bouts at 40% peak oxygen uptake using a cycle ergometer in a
      semirecumbent position [spontaneous breathing for 5 min and voluntary
      hyperventilation with or without inspiratory resistive breathing for 5 min
      (breathing frequency 50 breaths min-1 with a 50% duty cycle; inspiratory
      resistance 30% of maximal inspiratory pressure)]. Mean arterial blood pressure
      (MAP) was acquired using finger photoplethysmography. The MSNA was recorded via
      microneurography of the right median nerve at the cubital fossa. During leg cycle
      exercise with inspiratory resistive breathing, MSNA burst frequency was
      increased, accompanied by an increase in MAP in both men and women. Women,
      compared with men, had less of an increase in MAP (women +22.8 +/- 12.3 mmHg
      versus men +32.2 +/- 5.4 mmHg; P < 0.05) and MSNA burst frequency (women +9.6 +/-
      2.9 bursts min-1 versus men +14.6 +/- 6.4 bursts min-1 ; P < 0.05). These results
      suggest that the attenuated inspiratory muscle-induced metaboreflex during
      exercise in young women is attributable, in part, to a lesser sympathetic
      vasomotor outflow compared with men.

PMID- 29334158
TI  - Growth of liver allografts over time in pediatric transplant recipients.
AB  - The liver's capacity to grow in response to metabolic need is well known.
      However, long-term growth of liver allografts in pediatric recipients has not
      been characterized. A retrospective review of pediatric recipients at a single
      institution identified patients who had cross-sectional imaging at 1, 5, and 10
      years post-transplant. Using volumetric calculations, liver allograft size was
      calculated and percent SLV were compared across the different time points; 18
      patients ranging from 0.3 to 17.7 years old were identified that had imaging at 2
      or more time points. Measured liver volumes increased by 59% after 5 years and
      170% after 10 years. The measured liver volumes compared to calculated %SLV for
      these patients were 123 +/- 37%, 97 +/- 19%, and 118 +/- 27% at 1, 5, and 10
      years after transplant, respectively. Our data suggest that liver allografts in
      pediatric recipients increase along with overall growth, and reach SLVs for
      height and weight by 5 years post-transplantation. Additionally, as pediatric
      recipients grow, the livers appear to maintain appropriate SLV.

PMID- 29334159
TI  - A Gold(III) Pincer Ligand Scaffold for the Synthesis of Binuclear and
      Bioconjugated Complexes: Synthesis and Anticancer Potential.
AB  - Cyclometalated (C^N^C)AuIII complexes bearing functionalized N-heterocyclic
      carbene (NHC) ligands provide a high-yielding, modular route to bioconjugated and
      binuclear complexes. This methodology has been applied to the synthesis of
      bioconjugated complexes presenting biotin and 17alpha-ethynylestradiol vectors,
      as well as to the synthesis of bimetallic AuIII /AuI complexes. The in vitro
      antiproliferative activities of these compounds against various cancer cells
      lines depend on the linker length, with the longer linker being the most potent.
      The estradiol conjugate AuC6 Estra proved to be more toxic against the estrogen
      receptor positive (ER+) cancer cells than against the ER- cancer cells and non
      cancer cells. The bimetallic complex AuC6 Au was more selective for breast cancer
      cells with respect to a healthy cell standard than the monometallic complex
      AuNHC. The metal uptake study on cells expressing or not biotin and estrogen
      receptors revealed an improved and targeted delivery of gold for both the
      bioconjugated complexes AuC6 Biot and AuC6 Estra compared to the non-vectorised
      analogue AuNHC. The investigations of the interaction of the bioconjugates and
      bimetallic complexes with human telomeric G-quadruplex DNA using FRET-melting
      techniques revealed a reduced ability to stabilize this DNA structure with
      respect to the non-vectorised analogue AuNHC.

PMID- 29334160
TI  - Fine-Tuning of Molecular Packing and Energy Level through Methyl Substitution
      Enabling Excellent Small Molecule Acceptors for Nonfullerene Polymer Solar Cells
      with Efficiency up to 12.54.
AB  - A novel small molecule acceptor MeIC with a methylated end-capping group is
      developed. Compared to unmethylated counterparts (ITCPTC), MeIC exhibits a higher
      lowest unoccupied molecular orbital (LUMO) level value, tighter molecular
      packing, better crystallites quality, and stronger absorption in the range of 520
      740 nm. The MeIC-based polymer solar cells (PSCs) with J71 as donor, achieve high
      power conversion efficiency (PCE), up to 12.54% with a short-circuit current (JSC
      ) of 18.41 mA cm-2 , significantly higher than that of the device based on
      J71:ITCPTC (11.63% with a JSC of 17.52 mA cm-2 ). The higher JSC of the PSC based
      on J71:MeIC can be attributed to more balanced MUh /MUe , higher charge
      dissociation and charge collection efficiency, better molecular packing, and more
      proper phase separation features as indicated by grazing incident X-ray
      diffraction and resonant soft X-ray scattering results. It is worth mentioning
      that the as-cast PSCs based on MeIC also yield a high PCE of 11.26%, which is
      among the highest value for the as-cast nonfullerene PSCs so far. Such a small
      modification that leads to so significant an improvement of the photovoltaic
      performance is a quite exciting finding, shining a light on the molecular design
      of the nonfullerene acceptors.

PMID- 29334161
TI  - The Role of Neurosonology in the Diagnosis and Management of Patients with
      Carotid Artery Disease: A Review.
AB  - Carotid artery disease (CAD) is a common cause of ischemic stroke with high rates
      of recurrence. Carotid endarterectomy (CEA) or carotid artery stenting (CAS) are
      highly recommended for the secondary prevention of symptomatic CAD during the
      first 14 days following the index event of transient ischemic attack or minor
      stroke. CEA or CAS may also be offered in selected cases with severe asymptomatic
      stenosis. Herein, we review the utility of neurosonology in the diagnosis and pre
      /peri-interventional assessment of CAD patients who undergo carotid
      revascularization procedures. Carotid ultrasound may provide invaluable
      information on plaque echogenicity, ulceration, risk of thrombosis, and rupture.
      Transcranial Doppler or transcranial color-coded sonography may further assist by
      mapping collateral circulation, evaluating the impairment of vasomotor
      reactivity, detecting microembolization, or reperfusion hemorrhage in real time.
      Neurosonology examinations are indispensable bedside tools assisting in the
      diagnosis, risk stratification, peri-interventional monitoring, and follow-up of
      patients with CAD.

PMID- 29334162
TI  - Prevalence of metabolic syndrome in children with moderate to severe psoriasis
      treated with TNF inhibitors in comparison to conventional agents.
AB  - Association of childhood psoriasis with metabolic syndrome has not been studied
      well. TNF-alfa contributes to the inflammation seen in metabolic syndrome, and
      recently etanercept has shown to reduce the levels of inflammatory markers.
      Assessment of prevalence of metabolic syndrome in juvenile psoriasis patients in
      Kuwait. We included 236 patients with moderate to severe psoriasis below 18 years
      treated for at least 24 weeks with TNF inhibitors (Group A), and equal number of
      age and sex matched cases treated with conventional medications (Group B). The
      metabolic syndrome (MBS) was defined according to the International Diabetes
      Foundation (IDF 2007 criteria for children). Increased waist circumference was
      seen in 56.77% of cases in Group A. Triglyceridemia was less frequent in Group A.
      MBS was higher in Group B [41.52% vs. 50.42%, odds ratio (OR) 1.76, 95% CI 1.19
      2.41; p = .005]. Psoriasis is associated with higher prevalence of metabolic
      syndrome in children. Six months of anti TNF treatment showed lesser association
      with metabolic syndrome. With fasting blood glucose, and serum TG seen in
      significantly lesser number of patients in this group.

PMID- 29334163
TI  - Isomerically Pure Star-Shaped Triphenylene-Perylene Hybrids Involving Highly
      Extended pi-Conjugation.
AB  - The synthesis and characterization of a new type of a highly conjugated
      heterocyclic pi-chromophore, consisting of a central triphenylene core fused with
      three perylene monoimide units (star-shaped molecules), is described. By
      judicious bay functionalization with tert-butylphenoxy substituents, aggregation
      was completely prevented by using 1,1,2,2-tetrachloroethane, allowing for a
      straightforward purification and, for the very first time, the complete
      separation of the constitutional isomers by HPLC. Both isomers can be easily
      distinguished by means of several conventional spectroscopic techniques.
      Furthermore, we have illustrated the absence of supramolecular aggregates and
      enhanced processability by noncovalent functionalization of graphene substrates,
      showing an outstanding homogeneity and demonstrating a different doping behavior
      in both isomers, making it possible to distinguish them by Raman spectroscopy.

PMID- 29334164
TI  - Clinical evaluation of a novel fractional radiofrequency device for hair growth:
      Fractional radiofrequency for hair growth stimulation.
AB  - AGA is a common disorder. Different treatments are available to prevent hair loss
      and achieve hair growth with variable results. The purpose of the present study
      was to evaluate the efficacy and safety of a novel fractional radiofrequency (RF)
      device (HairLux, Innogen Technologies Ltd., Yokneam, Israel), to prevent hair
      loss and induce hair growth. Twenty-five patients received 10 fractional RF
      treatments every 2 weeks, and were followed up 2 months after the last treatment.
      All patients were evaluated by global photography. In 10 patients, blinded manual
      hair counts were performed. Patients demonstrated less hair shedding, fuller
      hair, and faster hair growth. There was an average increase of 31.6% in hair
      density (based on hair counts) and 18% increase in hair shaft thickness. All
      subjects tolerated the treatments well. The HairLux device is effective and safe
      for hair growth stimulation in AGA. Ten treatment sessions are recommended to
      maximize results.

PMID- 29334165
TI  - 3D Printing of Liquid Crystal Elastomeric Actuators with Spatially Programed
      Nematic Order.
AB  - Liquid crystal elastomers (LCEs) are soft materials capable of large, reversible
      shape changes, which may find potential application as artificial muscles, soft
      robots, and dynamic functional architectures. Here, the design and additive
      manufacturing of LCE actuators (LCEAs) with spatially programed nematic order
      that exhibit large, reversible, and repeatable contraction with high specific
      work capacity are reported. First, a photopolymerizable, solvent-free, main-chain
      LCE ink is created via aza-Michael addition with the appropriate viscoelastic
      properties for 3D printing. Next, high operating temperature direct ink writing
      of LCE inks is used to align their mesogen domains along the direction of the
      print path. To demonstrate the power of this additive manufacturing approach,
      shape-morphing LCEA architectures are fabricated, which undergo reversible planar
      to-3D and 3D-to-3D' transformations on demand, that can lift significantly more
      weight than other LCEAs reported to date.

PMID- 29334166
TI  - Investigating Nucleosome Accessibility for MNase, FeII  Peplomycin, and
      Duocarmycin B2 by Using Capillary Electrophoresis.
AB  - Capillary electrophoresis, coupled with DNA 5' Texas Red labeling, was used to
      investigate the ability of MNase, FeII peplomycin, and duocarmycin B2 to access
      the nucleosome. Distinct accessibility patterns of these species to the
      nucleosome were observed. MNase was completely prevented from approaching the
      nucleosome core and exhibited a higher site specificity for targeting DNA sites
      located close to the core region. Intercalation of peplomycin in the nucleosomal
      core region was highly suppressed, but reaction sites located at the ends of the
      nucleosomal core remained accessible, which implied flexibility of the core DNA
      end. Duocarmycin B2 was able to enter and react in the core region, although its
      alkylating efficiency decreased significantly.

PMID- 29334167
TI  - Cross-Linking/Mass Spectrometry for Studying Protein Structures and Protein
      Protein Interactions: Where Are We Now and Where Should We Go from Here?
AB  - Structural mass spectrometry (MS) is gaining increasing importance for deriving
      valuable three-dimensional structural information on proteins and protein
      complexes, and it complements existing techniques, such as NMR spectroscopy and X
      ray crystallography. Structural MS unites different MS-based techniques, such as
      hydrogen/deuterium exchange, native MS, ion-mobility MS, protein footprinting,
      and chemical cross-linking/MS, and it allows fundamental questions in structural
      biology to be addressed. In this Minireview, I will focus on the cross-linking/MS
      strategy. This method not only delivers tertiary structural information on
      proteins, but is also increasingly being used to decipher protein interaction
      networks, both in vitro and in vivo. Cross-linking/MS is currently one of the
      most promising MS-based approaches to derive structural information on very large
      and transient protein assemblies and intrinsically disordered proteins.

PMID- 29334168
TI  - Representing causal knowledge in environmental policy interventions: Advantages
      and opportunities for qualitative influence diagram applications.
AB  - This article develops and explores a methodology for using qualitative influence
      diagrams in environmental policy and management to support decision-making
      efforts that minimize risk and increase resiliency. Influence diagrams are
      representations of the conditional aspects of a problem domain. Their graphical
      properties are useful for structuring causal knowledge relevant to policy
      interventions and can be used to enhance inference and inclusivity of multiple
      viewpoints. Qualitative components of influence diagrams are beneficial tools for
      identifying and examining the interactions among the critical variables in
      complex policy development and implementation. Policy interventions on social
      environmental systems can be intuitively diagrammed for representing knowledge of
      critical relationships among economic, environmental, and social attributes.
      Examples relevant to coastal resiliency issues in the US Gulf Coast region are
      developed to illustrate model structures for developing qualitative influence
      diagrams useful for clarifying important policy intervention issues and enhancing
      transparency in decision making. Integr Environ Assess Manag 2018;14:381-394.
      Published 2018. This article is a US Government work and is in the public domain
      in the USA.

PMID- 29334169
TI  - Impact of baseline clinical and laboratory features on the risk of thrombosis in
      children with acute lymphoblastic leukemia: A prospective evaluation.
AB  - BACKGROUND: Children with acute lymphoblastic leukemia (ALL) have increased risk
      of thromboembolism (TE). However, the predictors of ALL-associated TE are as yet
      uncertain. OBJECTIVE: This exploratory, prospective cohort study evaluated the
      effects of clinical (age, gender, ALL risk group) and laboratory variables
      (hematological parameters, ABO blood group, inherited and acquired prothrombotic
      defects [PDs]) at diagnosis on the development of symptomatic TE (sTE) in
      children (aged 1 to <=18) treated on the Dana-Farber Cancer Institute ALL 05-001
      study. PROCEDURES: Samples collected prior to the start of ALL therapy were
      evaluated for genetic and acquired PDs (proteins C and S, antithrombin,
      procoagulant factors VIII (FVIII:C), IX, XI and von Willebrand factor antigen
      levels, gene polymorphisms of factor V G1691A, prothrombin gene G20210A and
      methylene tetrahydrofolate reductase C677T, anticardiolipin antibodies, fasting
      lipoprotein(a), and homocysteine). RESULTS: Of 131 enrolled patients (mean age
      [range] 6.4 [1-17] years) 70 were male patients and 20 patients (15%) developed
      sTE. Acquired or inherited PD had no impact on the risk of sTE. Multivariable
      analyses identified older age (odds ratio [OR] 1.13; 95% confidence interval
      [CI]: 1.01, 1.26) and non-O blood group (OR 3.64, 95% CI: 1.06, 12.51) as
      independent predictors for development of sTE. Patients with circulating blasts
      had higher odds of developing sTE (OR 6.66; 95% CI: 0.82, 53.85). CONCLUSION:
      Older age, non-O blood group, and presence of circulating blasts, but not PDs,
      predicted the risk of sTE during ALL therapy. We recommend evaluation of these
      novel risk factors in the development of ALL-associated TE. If confirmed, these
      easily accessible variables at diagnosis can help develop a risk-prediction model
      for ALL-associated TE.

PMID- 29334170
TI  - Representing causal knowledge in environmental policy interventions: Advantages
      and opportunities for qualitative influence diagram applications.
AB  - This article develops and explores a methodology for using qualitative influence
      diagrams in environmental policy and management to support decision making
      efforts that minimize risk and increase resiliency. Influence diagrams are
      representations of the conditional aspects of a problem domain. Their graphical
      properties are useful for structuring causal knowledge relevant to policy
      interventions and can be used to enhance inference and inclusivity of multiple
      viewpoints. Qualitative components of influence diagrams are beneficial tools for
      identifying and examining the interactions among the critical variables in
      complex policy development and implementation. Policy interventions on social
      environmental systems can be intuitively diagrammed for representing knowledge of
      critical relationships among economic, environmental, and social attributes.
      Examples relevant to coastal resiliency issues in the U.S. Gulf Coast region are
      developed to illustrate model structures for developing qualitative influence
      diagrams useful for clarifying important policy intervention issues and enhancing
      transparency in decision making. This article is protected by copyright. All
      rights reserved.

PMID- 29334171
TI  - Reaction Mechanism for Direct Cyclization of Linear C5 , C6 , and C7 Alkenes over
      H-ITQ-13 Zeolite Investigated Using Density Functional Theory.
AB  - Although dienes or trienes have been shown to be possible precursors for
      cyclization, direct cyclization of alkenes or alkoxides has not been
      systematically studied yet. Thus, the reaction mechanism of cyclization of linear
      alkenes over H-ITQ-13 was investigated here by density functional theory
      considering dispersive interactions (DFT-D). The similar free energy of different
      linear alkoxides of the same carbon number suggests that they can co-exist in the
      H-ITQ-13 intersection at 673.15 K during the methanol to olefins (MTO) process.
      The formation of linear alkenes by olefins methylation with methoxyl groups
      (ZOCH3 ), trimethyloxonium ions (TMO+ ), and methanol are kinetically more
      favorable than by dimerization of olefins. Linear alkoxides or alkenes prefer
      direct cyclization to cycloalkanes rather than hydride transfer to diene. This
      study provides new insight into the alkene cyclization and aromatization
      mechanisms in MTO process.

PMID- 29334172
TI  - Silica Nanoparticle-induced Cytokine Responses in BEAS-2B and HBEC3-KT Cells:
      Significance of Particle Size and Signalling Pathways in Different Lung Cell
      Cultures.
AB  - We have previously reported that silica nanoparticles (SiNPs) of nominal size 50
      nm (Si50) induce the pro-inflammatory cytokines CXCL8 and IL-6 in BEAS-2B cells,
      via mechanisms involving MAPK p38, TACE-mediated TGF-alpha release and the NF
      kappaB pathway. In this study, we examined whether these findings are cell
      specific or might be extended to another epithelial lung cell model, HBEC3-KT,
      and also to SiNPs of a smaller size (nominal size of 10 nm; Si10). The TEM
      average size of Si10 and Si50 was 10.9 and 34.7 nm, respectively. The surface
      area (BET) of Si10 was three times higher than for Si50 per mass unit. With
      respect to hydrodynamic size (DLS), Si10 in exposure medium showed a higher z
      average for the main peak than Si50, indicating more excessive agglomeration.
      Si10 strongly induced CXCL8 and IL-6, as assessed by ELISA and RT-PCR, and was
      markedly more potent than Si50, even when adjusted to equal surface area.
      Furthermore, Si10 was far more cytotoxic, measured as lactate dehydrogenase (LDH)
      release, than Si50 in both epithelial cell cultures. With respect to signalling
      pathways, Western analysis and experiments with and without inhibition of MAPK,
      TACE and NF-kappaB (synthetic inhibitors) revealed that p38-phosphorylation, TACE
      mediated TGF-alpha release and NF-kappaB activation seem to be important
      triggering mechanisms for both Si50 and Si10 in the two different lung epithelial
      cell cultures. In conclusion, the identified signalling pathways are suggested to
      be important in inducing cytokine responses in different epithelial cell types
      and also for various sizes of silica nanoparticles.

PMID- 29334173
TI  - Microfluidic Templated Multicompartment Microgels for 3D Encapsulation and
      Pairing of Single Cells.
AB  - Controlled encapsulation and pairing of single cells within a confined 3D matrix
      can enable the replication of the highly ordered cellular structure of human
      tissues. Microgels with independently controlled compartments that can
      encapsulate cells within separately confined hydrogel matrices would provide
      precise control over the route of pairing single cells. Here, a one-step
      microfluidic method is presented to generate monodisperse multicompartment
      microgels that can be used as a 3D matrix to pair single cells in a highly
      biocompatible manner. A method is presented to induce microgels formation on
      chip, followed by direct extraction of the microgels from oil phase, thereby
      avoiding prolonged exposure of the microgels to the oil. It is further
      demonstrated that by entrapping stem cells with niche cells within separate but
      adjacent compartments of the microgels, it can create complex stem cell niche
      microenvironments in a controlled manner, which can serve as a useful tool for
      the study of cell-cell interactions. This microfluidic technique represents a
      significant step toward high-throughput single cells encapsulation and pairing
      for the study of intercellular communications at single cell level, which is of
      significant importance for cell biology, stem cell therapy, and tissue
      engineering.

PMID- 29334174
TI  - Trichloroacetic acid (80%) as a chemical debridement method for chronic venous
      leg ulcers-A pilot study.
AB  - Debridement is essential for the optimal care of venous leg ulcers. Several
      debridement methods with different limitations may be deployed. Trichloroacetic
      acid (TCA) is used for several dermatological purposes. Its application as a
      chemical debridement method for leg ulcers has never been explored. We designed a
      prospective study to determine the role of 80% TCA solution as a chemical
      debridement method for leg ulcers, regarding efficacy and procedure-associated
      pain. Chronic venous leg ulcers were treated with 3 cycles of 80% TCA solution or
      curettage over 1 week. Pain and the mean percentage of fibrin and devitalized
      tissue covering wound bed were evaluated. At the end of the study, a trend
      towards larger fibrin mean reduction among the TCA treated ulcers was observed,
      although this difference was not statistically significant (P = .35). The mean
      pain score after TCA application was significantly reduced compared to pain after
      curettage alone (P < 0.001). TCA presented several advantages over mechanical
      debridement: it is a more selective debridement method, has haemostatic
      properties, and a simpler and faster application. The 80% TCA solution may be a
      cheap, simple, and considerably less-painful chemical debridement method for
      venous leg ulcers compared to classical mechanical debridement.

PMID- 29334175
TI  - Efficient Catalytic Oxidation of 5-Hydroxymethylfurfural to 2,5-Furandicarboxylic
      Acid by Magnetic Laccase Catalyst.
AB  - 2,5-Furandicarboxylic acid (FDCA) is a bio-based platform chemical for the
      production of polyethylene furanoate (PEF) and other valuable furanic chemicals.
      A magnetic laccase catalyst with (2,2,6,6-tetramethyl-piperidin-1-yl)oxyl (TEMPO)
      as the mediator has the remarkable capability of oxidizing 5
      hydroxymethylfurfural (HMF) to 2,5-furandicarboxylic acid (FDCA). Under optimal
      reaction conditions, a quantitative yield (90.2 %) of FDCA with complete HMF
      conversion was obtained after 96 h of reaction. More importantly, the magnetic
      laccase catalyst exhibited good recyclability and stability, maintaining 84.8 %
      of its original activity following six reuse cycles. This is the first report on
      the efficient catalytic oxidation of HMF to FDCA by using an immobilized enzyme
      catalyst.

PMID- 29334176
TI  - The effect of 22.5 kHz low-frequency contact ultrasound debridement (LFCUD) on
      lower extremity wound healing for a vascular surgery population: A randomised
      controlled trial.
AB  - The aim of this study was to compare changes in wound size and appearance and
      health complication rates in patients with vasculopathy and lower-extremity
      wounds treated with or without low-frequency contact ultrasound debridement
      (LFCUD) This study was a randomised controlled trial. The study was conducted in
      a vascular surgery service, including outpatient wound clinic and inpatient ward,
      in a tertiary care academic centre. In total, 70 patients with vasculopathy and
      lower-extremity wounds of mixed aetiology were enrolled in the trial; 68
      completed the study. Patients were randomised to receive LFCUD plus usual care (n
      = 33) or usual care (n = 37) at 4 weekly visits, and were followed thereafter for
      up to 12 wk. The main outcome measures included closed wounds, change in wound
      surface area (WSA), and wound appearance by the revised Photographic Wound
      Assessment Tool (revPWAT). After 4 weekly LFCUD treatments, patients in the LFCUD
      group had significantly better wound appearance (total revPWAT score) compared
      with the control group treated only with usual care (P = <0.05). LFCUD-treated
      wounds also had a significant reduction in WSA over 4 wk that was not found in
      the UC group. LFCUD treatment was also associated with a greater number of healed
      wounds, odds ratio 5.00 (95% CI 1.24-20.25), and fewer instances of wound
      deterioration. Weekly LFCUD applications to patients with significant
      vasculopathy resulted in superior healing outcomes when compared with current
      usual wound care practice.

PMID- 29334177
TI  - Polypropylene Nonwoven Fabric@Poly(ionic liquid)s for Switchable Oil/Water
      Separation, Dye Absorption, and Antibacterial Applications.
AB  - Pollutants in wastewater include oils, dyes, and bacteria, making wastewater
      cleanup difficult. Multifunctional wastewater treatment media consisting of
      poly(ionic liquid)-grafted polypropylene (PP) nonwoven fabrics (PP@PIL) are
      prepared by a simple and scalable surface-grafting process. The fabricated PP@PIL
      fabrics exhibit impressive switchable oil/water separation (eta>99 %) and dye
      absorption performance (q=410 mg g-1 ), as well as high antibacterial properties.
      The oil/water separation can be easily switched by anion exchanging of the PIL
      segments. Moreover, the multiple functions (oil/water separation, dye absorption,
      and antibacterial properties) occurred at the same time, and did not interfere
      with each other. The multifunctional fibrous filter can be easily regenerated by
      washing with an acid solution, and the absorption capacity is maintained after
      many recycling tests. These promising features make PIL-grafted PP nonwoven
      fabric a potential one-step treatment for multicomponent wastewater.

PMID- 29334178
TI  - Factors associated with perceived accuracy of the Undetectable = Untransmittable
      slogan among men who have sex with men: Implications for messaging scale-up and
      implementation.
AB  - INTRODUCTION: Recent research has shown high efficacy of HIV treatment for
      reducing the risk of HIV transmission to sexual partners. As the efficacy of
      treatment as prevention (TasP) has proliferated, a new messaging campaign,
      Undetectable = Untransmittable, has been gaining popularity. The purpose of this
      paper was to assess factors associated with the perceived accuracy of this TasP
      messaging strategy among a large and diverse sample of gay, bisexual, and other
      men who have sex with men (GBMSM) in order to inform subsequent efforts at large
      scale and implementation of the HIV prevention message. METHODS: We conducted a
      nationwide survey of GBMSM in the U.S. recruited from an online social networking
      site and a mobile sexual networking app. We analysed data from 12,222 GBMSM
      separately by HIV status to examine sociodemographic and behavioural factors
      associated with ratings of the accuracy of the Undetectable = Untransmittable
      message, which included the option to indicate not understanding what
      "undetectable" meant. RESULTS: Among HIV-negative and unknown men, multivariable
      linear regression indicated that being on pre-exposure prophylaxis (PrEP),
      identifying as gay or queer (versus bisexual or straight), recent serodiscordant
      condomless anal sex (CAS), testing every six months or more often, less concern
      about sexually transmitted infection (STI) infection, and lower perceived risk of
      HIV infection were the factors with the largest independent effect on rating the
      Undetectable = Untransmittable statement as more accurate. Fewer factors emerged
      as associated with accuracy ratings among HIV-positive participants-reporting an
      undetectable viral load, a lifetime acquired immune deficiency syndrome (AIDS)
      diagnosis, and lower concern about STI infection were the factors most strongly
      associated with rating the statement as more accurate. CONCLUSIONS: The findings
      of the current study highlight variability in the perceived accuracy of the
      Undetectable = Untransmittable message, suggesting potential subgroups who might
      benefit from targeted educational campaigns, perhaps broadcast utilizing sexual
      networking apps. Numerous factors, particularly among HIV-negative and unknown
      GBMSM, were associated with rating the message as more accurate. In particular,
      being on PrEP and testing regularly were two of the variables most strongly
      associated with higher accuracy ratings among HIV-negative GBMSM, suggesting HIV
      prevention services as potential points of intervention for increasing HIV
      knowledge and decreasing HIV stigma.

PMID- 29334179
TI  - Functionalized Nanoparticles Efficiently Enhancing the Targeted Delivery, Tumor
      Penetration, and Anticancer Activity of 7-Ethyl-10-Hydroxycamptothecin.
AB  - The enhanced permeability and retention (EPR) effect of tumors is much more
      complex than initially defined, and it alone is not sufficient for targeted
      delivery of nanosized agents. Meanwhile, poor tumor penetration is another major
      challenge for the treatment of solid tumors using nanoparticles. Development of
      delivery systems for SN38, the active metabolite of CPT-11 in human and a very
      potent anticancer molecule, has become an attractive research area. PEGx 
      p(HEMASN38)y (x and y are viable), a prodrug synthesized by using polyethylene
      glycol (PEG) as initiator and SN38 as monomer through atom transfer radical
      polymeration (ATRP) method, is previously reported. Using PEG2.4K -p(HEMASN38)3K
      as a model prodrug, herein an active-targeted strategy decorated with cys-arg-gly
      asp-lys (CRGDK), a peptide specifically binds to neuropilin-1 overexpressed by
      tumor vessels and tumor cells, is successfully established to further improve the
      delivery and efficacy of SN38. CRGDK-functionalized PEG2.4K -p(HEMASN38)3K (C
      SN38) nanoparticles and nonfunctionalized control (B-SN38) are prepared with two
      distinct sizes, 30 and 100 nm. Their physiochemical and biological
      characteristics are investigated in vitro and in vivo with multiple tumor models.
      It is demonstrated for the first time that CRGDK functionalization can be a
      promising strategy for efficient delivery of SN38, and C-SN38 is a potent drug
      candidate for the treatment of neuropilin-1 overexpressing tumors.

PMID- 29334180
TI  - Nitric Oxide Dependent Degradation of Polyethylene Glycol-Modified Single-Walled
      Carbon Nanotubes: Implications for Intra-Articular Delivery.
AB  - Polyethylene glycol (PEG)-modified carbon nanotubes have been successfully
      employed for intra-articular delivery in mice without systemic or local toxicity.
      However, the fate of the delivery system itself remains to be understood. In this
      study 2 kDa PEG-modified single-walled carbon nanotubes (PNTs) are synthesized,
      and trafficking and degradation following intra-articular injection into the knee
      joint of healthy mice are studied. Using confocal Raman microspectroscopy, PNTs
      can be imaged in the knee-joint and are found to either egress from the synovial
      cavity or undergo biodegradation over a period of 3 weeks. Raman analysis
      discloses that PNTs are oxidatively degraded mainly in the chondrocyte-rich
      cartilage and meniscus regions while PNTs can also be detected in the synovial
      membrane regions, where macrophages can be found. Furthermore, using murine
      chondrocyte (ATDC-5) and macrophage (RAW264.7) cell lines, biodegradation of PNTs
      in activated, nitric oxide (NO)-producing chondrocytes, which is blocked upon
      pharmacological inhibition of inducible nitric oxide synthase (iNOS), can be
      shown. Biodegradation of PNTs in macrophages is also noted, but after a longer
      period of incubation. Finally, cell-free degradation of PNTs upon incubation with
      the peroxynitrite-generating compound, SIN-1 is demonstrated. The present study
      paves the way for the use of PNTs as delivery systems in the treatment of
      diseases of the joint.

PMID- 29334181
TI  - Donor Variability in Growth Kinetics of Healthy hMSCs Using Manual Processing:
      Considerations for Manufacture of Cell Therapies.
AB  - Human mesenchymal stromal cells (hMSCs) are excellent candidates for cell therapy
      but their expansion to desired clinical quantities can be compromised by ex vivo
      processing, due to differences between donor material and process variation. The
      aim of this article is to characterize growth kinetics of healthy baseline
      "reference" hMSCs using typical manual processing. Bone-marrow derived hMSCs from
      ten donors are isolated based on plastic adherence, expanded, and analyzed for
      their growth kinetics until passage 4. Results indicate that hMSC density
      decreases with overall time in culture (p < 0.001) but no significant differences
      are observed between successive passages after passage 1. In addition, fold
      increase in cell number dropped between passage 1 and 2 for three batches, which
      correlated to lower performance in total fold increase and expansion potential of
      these batches, suggesting that proliferative ability of hMSCs can be predicted at
      an early stage. An indicative bounded operating window is determined between
      passage 1 and 3 (PDL < 10), despite the high inter-donor variability present
      under standardized hMSC expansion conditions used. hMSC growth profile analysis
      will be of benefit to cell therapy manufacturing as a tool to predict culture
      performance and attainment of clinically-relevant yields, therefore stratifying
      the patient population based on early observation.

PMID- 29334182
TI  - Designing 3D Biological Surfaces via the Breath-Figure Method.
AB  - The fabrication of biointerfaces that mimic cellular physiological environments
      is critical to understanding cell behaviors in vitro and for the design of tissue
      engineering. Breath figure is a self-assemble method that uses water droplets
      condensed from moisture as template and ends up with a highly ordered hexagonal
      pore array; this approach is used to fabricate various biological substrates.
      This progress report provides an overview of strategies to achieve topographical
      modifications and chemical-patterned arrays, such as modulation of the pore size,
      shape and selective decoration of the honeycomb holes. Using recent results in
      the biological fields, potential future applications and developments of
      honeycomb structures are commented upon.

PMID- 29334183
TI  - Engineering Polymersomes for Diagnostics and Therapy.
AB  - Engineered polymer vesicles, termed as polymersomes, confer a flexibility to
      control their structure, properties, and functionality. Self-assembly of
      amphiphilic copolymers leads to vesicles consisting of a hydrophobic bilayer
      membrane and hydrophilic core, each of which is loaded with a wide array of small
      and large molecules of interests. As such, polymersomes are increasingly being
      studied as carriers of imaging probes and therapeutic drugs. Effective delivery
      of polymersomes necessitates careful design of polymersomes. Therefore, this
      review article discusses the design strategies of polymersomes developed for
      enhanced transport and efficacy of imaging probes and therapeutic drugs. In
      particular, the article focuses on overviewing technologies to regulate the size,
      structure, shape, surface activity, and stimuli- responsiveness of polymersomes
      and discussing the extent to which these properties and structure of polymersomes
      influence the efficacy of cargo molecules. Taken together with future
      considerations, this article will serve to improve the controllability of
      polymersome functions and accelerate the use of polymersomes in biomedical
      applications.

PMID- 29334184
TI  - pH-Responsive PEG-Doxorubicin-Encapsulated Aza-BODIPY Nanotheranostic Agent for
      Imaging-Guided Synergistic Cancer Therapy.
AB  - Synergistic cancer therapy is of great interest for multiple advantages, such as
      excellent targeting accuracy, low side effects, and enhanced therapeutic
      efficiency. Herein, a near-infrared photosensitizer aza-BODIPY (AB) with high
      singlet oxygen quantum yield (PhiDelta = 82%) is designed and synthesized. With
      Schiff's base obtained from condensation reaction between doxorubicin (DOX) and
      polyethylene glycol-benzaldehyde (PEG-CHO) as the polymer matrix, aza-BODIPY is
      encapsulated to afford hydrophilic nanoparticles (DAB NPs). The DAB NPs exhibit
      high reactive oxygen species (ROS) generation rate and outstanding photothermal
      conversion efficiency (eta = 38.3%) under irradiation. In vivo fluorescence- and
      photothermal-imaging (PTI) results demonstrate that DAB NPs can specifically
      accumulate at tumor sites and serve as dual-modal imaging probe for cancer
      diagnosis. Particularly, triggered by acidic tumor microenvironment, the ?HC?N?
      bond of Schiff's base would be broken simultaneously, resulting in the efficient
      release of DOX from DAB NPs at tumor sites as well as enhancing the targeting
      performance of chemotherapeutics. Compared with free DOX and aza-BODIPY
      nanoparticles, DAB NPs can inhibit tumor growth more effectively through pH
      responsive photodynamic/photothermal/chemo synergistic therapy. This report may
      also present a practicable strategy to develop a pH-responsive nanotheranostic
      agent for tumor targeting, imaging, and therapy.

PMID- 29334185
TI  - Physical Properties of Implanted Porous Bioscaffolds Regulate Skin Repair:
      Focusing on Mechanical and Structural Features.
AB  - Porous bioscaffolds are applied to facilitate skin repair since the early 1990s,
      but a perfect regeneration outcome has yet to be achieved. Until now, most
      efforts have focused on modulating the chemical properties of bioscaffolds, while
      physical properties are traditionally overlooked. Recent advances in
      mechanobiology and mechanotherapy have highlighted the importance of
      biomaterials' physical properties in the regulation of cellular behaviors and
      regenerative processes. In skin repair, the mechanical and structural features of
      porous bioscaffolds are two major physical properties that determine therapeutic
      efficacy. Here, first an overview of natural skin repair with an emphasis on the
      major biophysically sensitive cell types involved in this multistage process is
      provided, followed by an introduction of the four roles of bioscaffolds as skin
      implants. Then, how the mechanical and structural features of bioscaffolds
      influence these four roles is discussed. The mechanical and structural features
      of porous bioscaffolds should be tailored to balance the acceleration of wound
      closure and functional improvements of the repaired skin. This study emphasizes
      that decoupling and precise control of the mechanical and structural features of
      bioscaffolds are significant aspects that should be considered in future
      biomaterial optimization, which can build a foundation to ultimately achieve
      perfect skin regeneration outcomes.

PMID- 29334186
TI  - Natural Humic-Acid-Based Phototheranostic Agent.
AB  - Humic acids, a major constituent of natural organic carbon resources, are
      naturally formed through the microbial biodegradation of animal and plant
      residues. Due to numerous physiologically active groups (phenol, carboxyl, and
      quinone), the biomedical applications of humic acid have been already
      investigated across different cultures for several centuries or even longer. In
      this work, sodium humate, the sodium salt of humic acid, is explored as
      phototheranostic agent for light-induced photoacoustic imaging and photothermal
      therapy based on intrinsic absorption in the near-infrared region. The purified
      colloidal sodium humate exhibits a high photothermal conversion efficiency up to
      76.3%, much higher than that of the majority of state-of-the-art photothermal
      agents including gold nanorods, Cu9 S5 nanoparticles, antimonene quantum dots,
      and black phosphorus quantum dots, leading to obvious photoacoustic enhancement
      in vitro and in vivo. Besides, highly effective photothermal ablation of HeLa
      tumor is achieved through intratumoral injection. Impressively, sodium humate
      reveals ultralow toxicity at the cellular and animal levels. This work promises
      the great potential of humic acids as light-mediated theranostic agents, thus
      expanding the application scope of traditional humic acids in biomedical field.

PMID- 29334188
TI  - Soft Artificial Bladder Detrusor.
AB  - Developing soft devices for invasive procedures bears great importance for human
      health. The softness and large strain actuation of responsive hydrogels promise
      the potential to fabricate soft devices, which can attach on and assist to the
      function of organs. The key challenges lie in the fabrication of soft devices
      with robust actuating ability and biocompatibility to the attached organ. This
      paper presents a solution that integrates the thermoresponsive hydrogel membrane
      with flexible electronics and silk scaffold into a balloon-like soft device. As
      an example, the actuation assisting function of this soft device for shrinking an
      animal bladder is presented. The mechanical behaviors of the balloon-like soft
      device are experimentally and theoretically investigated. The concepts are
      applicable to other applications such as soft implants, soft robotics, and
      microfluidics.

PMID- 29334189
TI  - A Multifunctional Micellar Nanoplatform with pH-Triggered Cell Penetration and
      Nuclear Targeting for Effective Cancer Therapy and Inhibition to Lung Metastasis.
AB  - The enhancement of cellular internalization and subsequent achievement of a
      nuclear targeting of nanocarriers play an important role in maximizing the
      therapeutic potency and minimizing the side effects of encapsulated drugs.
      Herein, a multifunctional micellar nanoplatform simultaneously with high cell
      penetration and nuclear targeting through pH-triggered surface charge reversal is
      presented. The miscellar system is constructed from poly(ethylene glycol)
      poly(epsilon-caprolactone) with 2,3-dimethylmaleic anhydride-Tat decoration
      (PECL/DA-Tat). DA groups are used to mask the positive charge of Tat to prolong
      blood circulation of the nanocarriers. In the mildly acidic environment of tumor
      tissue, the system exhibits ultrasensitive negative to positive charge reversal,
      facilitating the cell internalization and subsequent nuclear targeting. The
      chemotherapeutic 10-hydroxycamptothecin conjugated to methoxy polyethylene
      glycol, which is loaded in this micelle, obviously enhances cytotoxicity against
      tumor cells. The in vivo therapy in mice bearing 4T1 breast tumor reveals that
      the system has a significant enhancement of both the endocytosis and nuclear
      enrichment, showing a highly effective antitumor efficacy and inhibition to lung
      metastasis.

PMID- 29334187
TI  - Surveying the landscape of optogenetic methods for detection of protein-protein
      interactions.
AB  - Mapping the protein-protein interaction (PPi) landscape is of critical importance
      to furthering our understanding how cells and organisms function. Optogenetic
      methods, that is, approaches that utilize genetically encoded fluorophores or
      fluorogenic enzyme reactions, uniquely enable the visualization of biochemical
      phenomena in live cells with high spatial and temporal accuracy. Applying
      optogenetic methods to the detection of PPis requires the engineering of protein
      based systems in which an optical signal undergoes a substantial change when the
      two proteins of interest interact. In recent years, researchers have developed a
      number of creative and effective optogenetic methods that achieve this goal, and
      used them to further elaborate our map of the PPi landscape. In this review, we
      provide an introduction to the general principles of optogenetic PPi detection,
      and then provide a number of representative examples of how these principles have
      been applied. We have organized this review by categorizing methods based on
      whether the signal generated is reversible or irreversible in nature, and whether
      the signal is localized or nonlocalized at the subcellular site of the PPi. We
      discuss these techniques giving both their benefits and drawbacks to enable
      rational choices about their potential use. This article is categorized under:
      Laboratory Methods and Technologies > Imaging Laboratory Methods and Technologies
      > Macromolecular Interactions, Methods Analytical and Computational Methods >
      Analytical Methods.

PMID- 29334190
TI  - The effects of low levels of trivalent ions on a standard strain of Escherichia
      coli (ATCC 11775) in aqueous solutions.
AB  - Considering the ever-growing usage of trivalent salts in water treatment, for
      example, lanthanum salts in rare earth, AlCl3 and FeCl3 , the effects of
      different trivalent cations on the bacterium Escherichia coli (E. coli) ATCC
      11775 strain have been studied in aqueous solutions. From colony incubation
      studies, the colony-forming unit (CFU) densities were found to decrease
      significantly in the presence of even low levels (10-5  mol/L) of lanthanum
      chloride. This level of reduction in CFU number is comparable to the results
      obtained using the known bacteriocidal cationic surfactant, C14 TAB. By
      comparison, exposure of the cells to low levels of trivalent ion, aluminum and
      chromium ion solutions produced only modest reductions in CFU density. The
      results from the incubation studies suggest that the bacteriostatic mechanism of
      La3+ ions has similarities to that of the cationic surfactant, and different to
      that of the other trivalent ions. Size distribution and zeta potential
      measurements of E. coli cells and phospholipid vesicles in the presence of
      trivalent cations solutions suggested significant cell shrinkage probably caused
      by membrane disruption.

PMID- 29334191
TI  - Exogenous oestrogen inhibits genital transmission of cell-associated HIV-1 in
      DMPA-treated humanized mice.
AB  - INTRODUCTION: HIV affects more women than any other life-threatening infectious
      agent, and most infections are sexually transmitted. HIV must breach the female
      genital tract mucosal barrier to establish systemic infection, and clinical
      studies indicate virus more easily evades this barrier in women using depot
      medroxyprogesterone acetate (DMPA) and other injectable progestins for
      contraception. Identifying a potential mechanism for this association, we learned
      DMPA promotes susceptibility of wild-type mice to genital herpes simplex virus
      type 2 (HSV-2) infection by reducing genital tissue expression of the cell-cell
      adhesion molecule desmoglein-1 (DSG-1) and increasing genital mucosal
      permeability. Conversely, DMPA-mediated increases in genital mucosal permeability
      and HSV-2 susceptibility were eliminated in mice concomitantly administered
      exogenous oestrogen (E). To confirm and extend these findings, herein we used
      humanized mice to define effects of systemic DMPA and intravaginal (ivag) E
      administration on susceptibility to genital infection with cell-associated HIV-1.
      METHODS: Effects of DMPA or an intravaginal (ivag) E cream on engraftment of NOD
      scid-IL-2Rgcnull  (NSG) mice with human peripheral blood mononuclear cells
      (hPBMCs) were defined with flow cytometry. Confocal microscopy was used to
      evaluate effects of DMPA, DMPA and E cream, or DMPA and the pharmacologically
      active component of the cream on vaginal tissue DSG-1 expression and genital
      mucosal permeability to low molecular weight (LMW) molecules and hPBMCs. In other
      studies, hPBMC-engrafted NSG mice (hPBMC-NSG) received DMPA or DMPA and ivag E
      cream before genital inoculation with 106 HIV-1-infected hPBMCs. Mice were
      euthanized 10 days after infection, and plasma HIV-1 load quantified by qRT-PCR
      and splenocytes used to detect HIV-1 p24 antigen via immunohistochemistry and
      infectious virus via TZM-bl luciferase assay. RESULTS: Whereas hPBMC engraftment
      was unaffected by DMPA or E treatment, mice administered DMPA and E (cream or the
      pharmacologically active cream component) displayed greater vaginal tissue
      expression of DSG-1 protein and decreased vaginal mucosal permeability to LMW
      molecules and hPBMCs versus DMPA-treated mice. DMPA-treated hPBMC-NSG mice were
      also uniformly susceptible to genital transmission of cell-associated HIV-1,
      while no animal concomitantly administered DMPA and E cream acquired systemic HIV
      1 infection. CONCLUSION: Exogenous E administration reduces susceptibility of
      DMPA-treated humanized mice to genital HIV-1 infection.

PMID- 29334192
TI  - Digitalizing Self-Assembled Chiral Superstructures for Optical Vortex Processing.
AB  - Cholesteric liquid crystal (CLC) chiral superstructures exhibit unique features;
      that is, polychromatic and spin-determined phase modulation. Here, a concept for
      digitalized chiral superstructures is proposed, which further enables the
      arbitrary manipulation of reflective geometric phase and may significantly
      upgrade existing optical apparatus. By encoding a specifically designed binary
      pattern, an innovative CLC optical vortex (OV) processor is demonstrated. Up to
      25 different OVs are extracted with equal efficiency over a wavelength range of
      116 nm. The multiplexed OVs can be detected simultaneously without mode crosstalk
      or distortion, permitting a polychromatic, large-capacity, and in situ method for
      parallel OV processing. Such complex but easily fabricated self-assembled chiral
      superstructures exhibit versatile functionalities, and provide a satisfactory
      platform for OV manipulation and other cutting-edge territories. This work is a
      vital step towards extending the fundamental understanding and fantastic
      applications of ordered soft matter.

PMID- 29334193
TI  - Managing risk of surgical procedures in pediatric transplant recipients taking
      mTOR inhibitors: What is the optimal strategy?

PMID- 29334194
TI  - Enrollment in early-phase clinical trials in pediatric oncology: The experience
      at Institut Curie.
AB  - BACKGROUND: The European Paediatric Regulation was introduced in 2007 to
      facilitate access to new medicines for children. Our study explored accessibility
      of early-phase trials in pediatric oncology, in line with the European Paediatric
      Regulation, to identify the reasons for not inviting patients to participate,
      parents' refusal, or inclusion failure. PROCEDURE: We conducted a retrospective
      chart review at Institut Curie, Paris, for all pediatric patients whose cancer
      progressed despite known effective treatments between July 2010 and December
      2013. RESULTS: Out of 100 patients in the palliative phase, 52 received one or
      more invitations to participate in early-phase trials. Twenty parents declined
      the invitation, mainly prioritizing quality of life or fearing constraints.
      Fourteen inclusions failed despite parental approval, mostly due to rapid
      clinical deterioration. Five patients received no invitations because no early
      phase trials were available. Major reasons for noninclusion in the 43 remaining
      patients were presence of exclusion criteria or other physical factors,
      preference for conventional treatment, constraints, psychological factors, and
      follow-up in another hospital after moving. CONCLUSIONS: The Paediatric
      Regulation has led to increased availability of early-phase trials. Better timing
      of the proposal, designing less constraining early-phase trials, reducing waiting
      lists, and improving information for parents and children would facilitate
      pediatric access to new medicines.

PMID- 29334195
TI  - Exoproteome Profiling Reveals the Involvement of the Foldase PrsA in the Cell
      Surface Properties and Pathogenesis of Staphylococcus aureus.
AB  - Staphylococcus aureus is a bacterial pathogen that produces and exports many
      virulence factors that cause diseases in humans. PrsA, a membrane-bound foldase,
      is expressed ubiquitously in Gram-positive bacteria and required for the folding
      of exported proteins into a stable and active structure. To understand the
      involvement of PrsA in posttranslocational protein folding in S. aureus, a PrsA
      deficient mutant of S. aureus HG001 was constructed. Using isobaric tags for
      relative and absolute quantification (iTRAQ)-based mass spectrometry analyses,
      the exoproteomes of PrsA mutant and wild type S. aureus were comparatively
      profiled, and 163 cell wall-associated proteins and 67 exoproteins with altered
      levels have been identified in the PrsA-deficient mutant. Bioinformatics analyses
      further reveal that prsA deletion altered the amounts of proteins that are
      potentially involved in the regulation of cell surface properties and bacterial
      pathogenesis. To determine the relevancy of our findings, we investigated the
      functional consequence of prsA deletion in S. aureus. PrsA deficiency can enhance
      bacterial autoaggregation and increase the adhesion ability of S. aureus to human
      lung epithelial cells. Moreover, mice infected with PrsA-deficient S. aureus had
      a better survival rate compared with those infected with the wild-type S. aureus.
      Collectively, our findings reveal that PrsA is required for the
      posttranslocational folding of numerous exported proteins and critically affects
      the cell surface properties and pathogenesis of S. aureus.

PMID- 29334196
TI  - Microfluidic Tumor-Vascular Model to Study Breast Cancer Cell Invasion and
      Intravasation.
AB  - Cancer is a major leading cause of disease-related death in the world. The severe
      impact of cancer can be attributed to poor understanding of the mechanisms
      involved in earliest steps of the metastatic cascade, specifically invasion into
      the surrounding stroma and intravasation into the blood capillaries. However,
      conducting integrated biological studies of invasion and intravasation have been
      challenging, within in vivo models and traditional in vitro assay, due to
      difficulties in establishing a precise tumor microenvironment. To that end, in
      this work, a novel 3D microfluidic platform comprised of concentric three-layer
      cell-laden hydrogels for simultaneous investigation of breast cancer cell
      invasion and intravasation as well as vasculature maturation influenced by tumor
      vascular crosstalk is developed. It was demonstrated that the presence of
      spontaneously formed vasculature enhance MDA-MB-231 invasion into the 3D stroma.
      Following invasion, cancer cells are visualized intravasating into the outer
      vasculature. Additionally, invading cancer cells significantly reduce vessel
      diameter while increasing permeability, consistent with previous in vivo studies.
      Major signaling cytokines involved in tumor-vascular crosstalk that govern cancer
      cell invasion and intravasation are further identified. Taken together, this
      platform will enable unique insights of critical biological events within the
      metastatic cascade, with significant potential for developing efficient cancer
      therapeutics.

PMID- 29334198
TI  - Enzyme-Based Glucose Sensor: From Invasive to Wearable Device.
AB  - Blood glucose concentration is a key indicator of patients' health, particularly
      for symptoms associated with diabetes mellitus. Because of the large number of
      diabetic patients, many approaches for glucose measurement have been studied to
      enable continuous and accurate glucose level monitoring. Among them,
      electrochemical analysis is prominent because it is simple and quantitative. This
      technology has been incorporated into commercialized and research-level devices
      from simple test strips to wearable devices and implantable systems. Although
      directly monitoring blood glucose assures accurate information, the invasive
      needle-pinching step to collect blood often results in patients (particularly
      young patients) being reluctant to adopt the process. An implantable glucose
      sensor may avoid the burden of repeated blood collections, but it is quite
      invasive and requires periodic replacement of the sensor owing to biofouling and
      its short lifetime. Therefore, noninvasive methods to estimate blood glucose
      levels from tears, saliva, interstitial fluid (ISF), and sweat are currently
      being studied. This review discusses the evolution of enzyme-based
      electrochemical glucose sensors, including materials, device structures,
      fabrication processes, and system engineering. Furthermore, invasive and
      noninvasive blood glucose monitoring methods using various biofluids or blood are
      described, highlighting the recent progress in the development of enzyme-based
      glucose sensors and their integrated systems.

PMID- 29334197
TI  - Increased non-AIDS mortality among persons with AIDS-defining events after
      antiretroviral therapy initiation.
AB  - INTRODUCTION: HIV-1 infection leads to chronic inflammation and to an increased
      risk of non-AIDS mortality. Our objective was to determine whether AIDS-defining
      events (ADEs) were associated with increased overall and cause-specific non-AIDS
      related mortality after antiretroviral therapy (ART) initiation. METHODS: We
      included HIV treatment-naive adults from the Antiretroviral Therapy Cohort
      Collaboration (ART-CC) who initiated ART from 1996 to 2014. Causes of death were
      assigned using the Coding Causes of Death in HIV (CoDe) protocol. The adjusted
      hazard ratio (aHR) for overall and cause-specific non-AIDS mortality among those
      with an ADE (all ADEs, tuberculosis (TB), Pneumocystis jiroveci pneumonia (PJP),
      and non-Hodgkin's lymphoma (NHL)) compared to those without an ADE was estimated
      using a marginal structural model. RESULTS: The adjusted hazard of overall non
      AIDS mortality was higher among those with any ADE compared to those without any
      ADE (aHR 2.21, 95% confidence interval (CI) 2.00 to 2.43). The adjusted hazard of
      each of the cause-specific non-AIDS related deaths were higher among those with
      any ADE compared to those without, except metabolic deaths (malignancy aHR 2.59
      (95% CI 2.13 to 3.14), accident/suicide/overdose aHR 1.37 (95% CI 1.05 to 1.79),
      cardiovascular aHR 1.95 (95% CI 1.54 to 2.48), infection aHR (95% CI 1.68 to
      2.81), hepatic aHR 2.09 (95% CI 1.61 to 2.72), respiratory aHR 4.28 (95% CI 2.67
      to 6.88), renal aHR 5.81 (95% CI 2.69 to 12.56) and central nervous aHR 1.53 (95%
      CI 1.18 to 5.44)). The risk of overall and cause-specific non-AIDS mortality
      differed depending on the specific ADE of interest (TB, PJP, NHL). CONCLUSIONS:
      In this large multi-centre cohort collaboration with standardized assignment of
      causes of death, non-AIDS mortality was twice as high among patients with an ADE
      compared to without an ADE. However, non-AIDS related mortality after an ADE
      depended on the ADE of interest. Although there may be unmeasured confounders,
      these findings suggest that a common pathway may be independently driving both
      ADEs and NADE mortality. While prevention of ADEs may reduce subsequent death due
      to NADEs following ART initiation, modification of risk factors for NADE
      mortality remains important after ADE survival.

PMID- 29334199
TI  - Comparison of Cabergoline and Quinagolide in Prevention of Severe Ovarian
      Hyperstimulation Syndrome among Patients Undergoing Intracytoplasmic Sperm
      Injection.
AB  - Background: The aim of the current study is to compare quinagolide with
      cabergoline in prevention of ovarian hyperstimulation syndrome (OHSS) among high
      risk women undergoing intracytoplasmic sperm injection (ICSI). MATERIALS AND
      METHODS: This randomized clinical trial study was performed from March 2015 to
      February 2017. One hundred and twenty six women undergoing ICSI who were at high
      risk of developing OHSS (having over 20 follicles of >12 mm), were randomized
      into two groups. The first group received cabergoline 0.5 mg and the second group
      received quinagolide 75 mg every day for 7 days commencing on the day of
      gonadotropin-releasing hormone (GnRH) agonist administration. Then OHSS symptoms
      as well as their severity were assessed according to standard definition, 3 and 6
      days after GnRH agonist administration. Ascites were determined by trans-vaginal
      ultrasound. Other secondary points were the number of oocytes and the number of
      embryos and their quality. Quantitative and qualitative data were analyzed using
      Student's t test, and Chi-square or fisher's exact test, respectively. A P<0.05
      was considered statistically significant. RESULTS: The incidence of severe OHSS
      in the quinagolide-treated group was 3.1% while it was 15.8% in
      cabergolinetreated subjects (P<0.001). Ascites were less frequent after treatment
      with Quinagolide as compared to cabergoline (21.9% vs. 61.9%, respectively)
      (P=0.0001). There was no significant statistical deferences between the two
      groups in terms of mean age, number of oocytes, metaphase I and metaphase II
      oocytes, and germinal vesicles. There was a significant difference between
      cabergoline and quinagolide groups regarding the embryo number (P=0.037) with
      cabergoline-treated group showing a higher number of embryos. But, the number of
      good quality embryo in quinagolide- treated individuals was significantly higher
      than that of the cabergoline-treated group (P=0.001). CONCLUSION: Quinagolide
      seems to be more effective than Cabergoline in prevention of OHSS in high-risk
      patients undergoing ICSI. (Registration number: IRCT2016053128187N1).

PMID- 29334200
TI  - Comparative Effectiveness of Antidepressant Medication versus Psychological
      Intervention on Depression Symptoms in Women with Infertility and Sexual
      Dysfunction.
AB  - Background: Fertility loss is considered as a challenging experience. This study
      was conducted to compare the effectiveness of antidepressant medication and
      psychological intervention on depression symptoms in women with infertility and
      sexual dysfunctions (SD). MATERIALS AND METHODS: This randomized, controlled
      clinical trial study was completed from December 2014 to June 2015 in Babol,
      Iran. Of the 485 participants, 93 were randomly assigned in a 1:1:1 ratio to
      psychosexual therapy (PST), bupropion extended-release (BUP ER) at a dose of 150
      mg/d, and control (no intervention) groups. The beck depression inventory (BDI)
      was completed at the beginning and end of the study. Duration of study was eight
      weeks. Statistical analyses were performed by using paired-test and analysis of
      covariance. RESULTS: The mean depression score on the BDI was 22.35 +/- 8.70 in
      all participants. Mean BDI score decreased significantly in both treatment groups
      (PST: P<0.0001, BUP: P<0.002) from baseline to end of the study, whereas intra
      individual changes in BDI score were not significant in the control group. The
      decrease in mean BDI score was greater with PST compared to BUP treatment
      (P<0.005) and the control group (P<0.0001). The PST group showed greater
      improvement in depression levels (severe to moderate, moderate to mild) in
      comparison with the two other groups (P<0.001). Drug treatment was well tolerated
      by the participants in the BUP group. CONCLUSION: PST can be a reliable
      alternative to BUP ER for relieving depression symptoms in an Iranian population
      of women with infertility and SD (Registration number: IRCT2015042721955N2).

PMID- 29334201
TI  - Comparison of The Effects of A Positive Reappraisal Coping Intervention and
      Problem-Solving Skills Training on Depression during The Waiting Period of The
      Result of Intrauterine Insemination Treatment: A Randomized Control Trial.
AB  - Background: The outcomes of fertility treatments are unpredictable, and levels of
      depressive symptoms increase in patients during the waiting period of the result
      of intrauterine insemination (IUI) treatment. The aim of this study was to
      compare the effects of a positive reappraisal coping intervention (PRCI) and
      problem-solving skills training (PSS) on depression during the waiting period of
      the result of IUI Treatment. MATERIALS AND METHODS: This randomized control
      clinical trial was done among 108 women undergoing IUI treatment. In the control
      group, the women received routine care. In the PRCI group, women attended two
      training sessions and were asked to complete coping thoughts cards and fill out
      daily monitoring forms during the waiting period. In the PSS group, PSS were
      taught over three sessions. The depression was measured by the beck depression
      inventory. RESULTS: On the 10thth day of the IUI waiting period, there were
      significant differences between the control group (21.42 +/- 11.42) and the PSS
      group (12.52 +/- 8.05) and PRCI groups (13.14 +/- 9.7) (P<0.001), but no
      significant difference between the PRCI group and the PSS group. CONCLUSION:
      According to the results of this randomized control trial there is no difference
      between a PRCI and PSS on depression during the waiting period of the result of
      IUI treatment. This suggests that both interventions can be used to help
      infertile women combat depression during the waiting period of the result of
      fertility treatments (Registration number: IRCT2016020926490N1).

PMID- 29334202
TI  - Lifestyle-Related Factors Associated with Reproductive Health in Couples Seeking
      Fertility Treatments: Results of A Pilot Study.
AB  - Background: The objective of this pilot study was to evaluate the feasibility of
      conducting a larger prospective cohort study, which will aim at determining the
      independent contribution of male and female lifestyle-related factors to assisted
      reproductive technology (ART) success. The study also examined whether couples
      seeking fertility treatments present lifestyle-related factors that may interfere
      with their reproductive health. MATERIALS AND METHODS: This prospective pilot
      study was conducted in a fertility clinic between May 2015 and February 2016.
      Feasibility factors evaluated were recruitment rates, compliance with the
      protocol, retention rate and ART outcomes at six-month follow-up. Anthropometric
      profile and lifestyle habits of both partners were evaluated before the beginning
      of infertility treatments. RESULTS: We approached 130 eligible infertile couples.
      Among them, 32 (25%) agreed to participate and 28 (88%) complied with the
      protocol. At six-month follow-up, seven couples (25%) did not start, or stop,
      infertility treatments and 13 couples (62%) achieved a clinical pregnancy. Among
      the 28 couples included in the analyses, 16% of the partners were obese and 23%
      had abdominal obesity. The majority of the subjects were still drinking alcohol
      (84%). Sixty-eight percent of women needed improvement in their diet (vs. 95% of
      men, P=0.05) and none of them achieved the Canadian recommendations for physical
      activity (vs. 33% of men, P=0.001). Moreover, 35% of the partners had a poor
      sleep quality. Overall, women presented a worse reproductive health profile than
      men, with 3.1 and 2.4 out of seven adverse factors, respectively (P=0.04).
      CONCLUSION: Conducting a large prospective cohort study in our fertility clinic
      will be feasible but recruitment and compliance with the protocol need to be
      improved. Many women and men seeking fertility treatments present unfavourable
      lifestyle-related factors that may explain, at least partially, their
      difficulties in conceiving.

PMID- 29334203
TI  - Modeling In Vitro Fertilization Data Considering Multiple Outcomes Observed among
      Iranian Infertile Women.
AB  - Background: Women undergoing in vitro fertilization (IVF) cycles should
      successfully go through multiple points during the procedure (i.e., implantation,
      clinical pregnancy, no spontaneous abortion and delivery) to achieve live births.
      In this study, data from multiple cycles and multiple points during the IVF cycle
      are collected for each individual to model the effects of factors associated with
      success at different stages of IVF cycles in Iranian infertile women. MATERIALS
      AND METHODS: This historical cohort study includes 996 assisted reproductive
      technology (ART) cycles of 511 infertile women. Covariates considered in this
      study were women's age, type of cycle (fresh or frozen embryo transfer), number
      of embryos transferred and having polycystic ovarian syndrome during IVF cycles.
      Generalized estimating equations were used for calculation of odds ratio (OR) and
      95% confidence intervals (95% CI) of success at different stages during IVF
      cycles. Cluster-weighted generalized estimating equations (CWGEE) was also fitted
      to handle informative cluster size. RESULTS: After adjusting for potential
      confounders, it was seen that receiving frozen embryo transfer was associated
      with higher odds of success compared to receiving fresh embryo transfer (adj OR:
      2.26, 95% CI: 1.66-3.07); however, cycles with fresh embryo transfer exhibited
      better results in clinical pregnancy compared to those receiving frozen embryo.
      Being in the age category of 38 to 40 was associated with lower odds of success
      compared to the reference category (p<35) in CWGEE model (adj OR: 0.67, 95% CI:
      0.45-1.00). The number of embryos transferred was positively associated with the
      odds of success in CWGEE (adj OR: 1.21, 95% CI: 1.03-1.42) as well as the GEE
      model. CONCLUSION: Receiving frozen embryo was positively associated with odds of
      success compared to cycles with fresh embryo. The number of embryos transferred
      and women's age were significantly associated with odds of success.

PMID- 29334204
TI  - Detection of Chlamydia trachomatis in Pap Smear Samples from South Khorasan
      Province of Iran.
AB  - Background: Chlamydia trachomatis (CT), the most common bacterial sexually
      transmitted infection (STI), leads to pelvic inflammatory disease, infertility
      and chronic pelvic pain in women as well as an increased risk of vertical
      transmission, conjunctivitis and pneumonitis in infants. It may also be a co
      factor along with human papillomavirus (HPV) in cervical cancer progression. We
      aimed to determine the prevalence of CT genotypes in genital specimens of women
      from South Khorasan, Iran and to test the association between CT and cytology
      statistics. MATERIALS AND METHODS: This was a cross-sectional study on 248 Pap
      smear samples from women who visited a gynecologist for routine Pap smear testing
      in South Khorasan province. Nested polymerase chain reaction (PCR) was used to
      test the residual fluids of Pap smears for CT-DNA after cytological examination.
      Direct sequencing, alignment and phylogenic analyses were performed on eight
      samples to identify their genotypes. RESULTS: The mean age of patients was 37.54
      +/- 5.21 years. Most samples had a normal cytology (214 cases, 86.29%). Overall,
      31 samples were positive for CT infection (12.5%) of which 20 (9.34%) were normal
      and 11 (32.35%) were abnormal, with the frequency difference being significant
      (P=0.022). The co-infection of CT/HPV in total was identified in 14 cases (5.6%).
      The results of sequencing eight samples out of the 31 CT positive samples
      revealed the detection of genotypes D and E, each with four cases. CONCLUSION: We
      show that a high prevalence of genital CT infection is present in women with both
      normal and abnormal cytology; however, the higher prevalence among women in the
      abnormal group may indicate its involvement in cervical neoplasia.

PMID- 29334205
TI  - Overexpression of Endometrial Estrogen Receptor-Alpha in The Window of
      Implantation in Women with Unexplained Infertility.
AB  - Background: Failure in the endometrial receptivity may account for a significant
      number of infertility cases including unexplained infertility in women. Reduction
      in the endometrial estrogen receptor-alpha (ER-alpha) expression during
      implantation may be a critical event that coincides with the expression of
      specific genes and the formation of a receptive endometrium. The aim of the
      present study was to assess the expression of ER-alpha in the mid-secretory phase
      in the endometrium of women with unexplained infertility. MATERIALS AND METHODS:
      This case-control study was carried out on randomly selected fertile (n=10) and
      infertile (n=16) women whose source of infertility remained unexplained. We
      evaluated the expression of ER-alpha and glycodelin- A (GdA) through mRNA level
      measurement with real-time polymerase chain reaction (PCR) in the endometrium of
      fertile women and patients suffering from unexplained infertility and fertile
      women. Endometrial biopsies of each subject were collected during a single
      menstrual cycle 7 days after the peak of luteinizing hormone (LH+7). RESULTS:
      Endometrial expression level of ER-alpha was significantly (P<0.05) higher in the
      patients with unexplained infertility compared to the control. Significantly
      (P<0.05) lower levels of GdA expression were seen in women with unexplained
      infertility. A statistically non-significant negative correlation was observed
      between ER-alpha and GdA mRNA expression. CONCLUSION: Our findings demonstrate
      that reduction in the endometrial GdA expression is associated with elevated
      expression of ER-alpha in mid-luteal phase. Disruption in the endometrial ER
      alpha expression, which leads to defects in uterine receptivity, may contribute
      to unexplained infertility.

PMID- 29334206
TI  - Decreased Expression of Arginine-Phenylalanine-Amide-Related Peptide-3 Gene in
      Dorsomedial Hypothalamic Nucleus of Constant Light Exposure Model of Polycystic
      Ovarian Syndrome.
AB  - Background: An abnormality in pulse amplitude and frequency of gonadotropin
      releasing hormone (GnRH) secretion is the most characteristics of polycystic
      ovarian syndrome (PCOS). On the other hand, arginine-phenylalanine-amide
      (RFamide)-related peptide-3 (RFRP3) inhibits the secretion of GnRH in mammalian
      hypothalamus. The current study performed in order to investigate the expression
      of RFRP3 mRNA in the dorsomedial hypothalamic nucleus (DMH) after the induction
      of PCOS in a rat model of constant light exposure, and the possible role of
      parity on occurrence of PCOS. MATERIALS AND METHODS: In the experimental study,
      female nulliparous (n=12) and primiparous (n=12) rats were randomly subdivided
      into control and PCOS subgroups (n=6). PCOS were induced by 90 days exposure to
      constant light. After 90 days, blood, brain, and ovaries were sampled. Serum
      levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), and
      testosterone were evaluated. In addition, six adult female ovariectomized rats as
      a control of real-time polymerase chain reaction (PCR) tests were prepared and in
      the DMH of all rats, the relative mRNA expression of RFRP3 was assessed. RESULTS:
      Histological evaluation of ovaries represented the polycystic features. In
      addition, serum concentrations of testosterone in the PCOS subgroups were more
      than the controls (P<0.05). Furthermore, the relative expression of RFRP3 mRNA in
      PCOS subgroups was lower than the controls (P<0.05). CONCLUSION: Constant light
      model of the PCOS-induced rats decreased the gene expression of RFRP3 in the DMH
      that suggests the decrease of RFRP3 may reduce its inhibitory effect on GnRH
      during the PCOS pathogenesis. This effect was stronger in the nulliparous rats
      than the primiparous.

PMID- 29334207
TI  - Screening for Causative Mutations of Major Prolificacy Genes in Iranian Fat
      Tailed Sheep.
AB  - Background: The presence of different missense mutations in sheep breeds have
      shown that the bone morphogenetic protein receptor 1B (BMPR1B), bone
      morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9) genes
      play a vital role in ovulation rate and prolificacy in ewes. Therefore, the
      present study aims to investigate BMPR1B, BMP15 and GDF9 gene mutations in
      prolific ewes of Iranian fat-tailed Lori-Bakhtiari sheep. MATERIALS AND METHODS:
      In the present experimental study, genomic DNA was extracted from whole blood of
      10 prolific Lori-Bakhtiari ewes with at least two twinning records in the first
      four parities to identify point mutations of the BMPR1B, BMP15 and GDF9 genes,
      using DNA sequencing. RESULTS: The results obtained from DNA sequencing showed a
      new synonymous mutation (g.66496G>A) in exon 8 of the BMPR1B gene, without any
      amino acid change. Sequencing of the BMP15 gene revealed a deletion of 3 bp
      (g.656_658delTTC) in exon 1, leading to an amino acid deletion (p.Leu19del). Four
      single nucleotide polymorphisms (G1:g.2118G>A, G2:g.3451T>C, G3:g.3457A>G and
      G4:g.3701G>A), were detected in exons 1 and 2 of the GDF9 gene, two of which
      caused amino acid substitutions (G1: p.87Arg>His and G4: p.241Glu>Lys). These
      amino acid alterations are proposed to have a benign impact on structure and
      function of the GDF9 polypeptide sequence. CONCLUSION: Three major prolificacy
      genes (BMPR1B, BMP15 and GDF9) were polymorphic in Lori-Bakhtiari sheep, although
      none of the major causative mutation was detected in this sheep type. Further
      studies using high throughput methods such as genome-wide association study
      (GWAS) and evaluation of other candidate genes are necessary in the future.

PMID- 29334208
TI  - Effects of Crocin on The Pituitary-Gonadal Axis and Hypothalamic Kiss-1 Gene
      Expression in Female Wistar Rats.
AB  - Background: Saffron (Crocus sativus L.) has been traditionally used as a spice
      for coloring and flavoring in some countries cuisine. One of the main components
      of saffron is Crocin. Recent research have shown that crocin has various
      pharmacological effects. The aim of this study was to assess the effects of
      crocin on the Pituitary-Gonadal axis and Kiss-1 gene expression in hypothalamus
      and ovarian tissue organization in female Wistar rats. MATERIALS AND METHODS: In
      this experimental study, 18 adult female Wistar rats were randomly divided into
      three groups. Control group received normal saline and experimental groups
      received two different doses of crocin (100 and 200 mg/kg) every two days for 30
      days. After the treatment period, blood samples were obtained from the heart and
      centrifuged. Next, the serum levels of follicle-stimulating hormone (FSH) and
      luteinizing hormone (LH), estrogen and progesterone hormones were measured by
      ELISA assay. The ovarian tissues were removed and fixed for histological
      investigation. The hypothalamic Kiss-1 gene expression was measured using real
      time polymerase chain reaction (PCR). All data were analyzed using one-way ANOVA.
      RESULTS: A significant reduction (P=0.038) in the number of atretic graafian
      follicles (0.5 +/- 0.31) was observed in rats treated with 200 mg/kg crocin. In
      addition, estrogen concentration in experimental groups (35.04 +/- 0.85 and 36.18
      +/- 0.69 in crocin 100 and 200 mg/kg groups, respectively) compared to control
      group (38.35 +/- 0.64) and progesterone concentration in rats treated with crocin
      200 mg/kg (2.06 +/- 0.07) compared to control group (2.16 +/- 0.04),
      significantly decreased. Interestingly, relative expressions of Kiss-1 mRNA
      significantly decreased in experimental groups (0.00053 +/- 0.00051 and 0.0011 +/
      0.00066 in crocin 100 and 200 mg/kg groups, respectively) (P=0.000) compared to
      control group (1 +/- 0). CONCLUSION: Crocin, at hypothalamic level, reduces Kiss
      1 gene expression and it can prevent follicular atresia and reduce serum levels
      of estrogen and progesterone.

PMID- 29334209
TI  - Comparison of The Effects of Vitrification on Gene Expression of Mature Mouse
      Oocytes Using Cryotop and Open Pulled Straw.
AB  - Background: Oocyte cryopreservation is an essential part of the assisted
      reproductive technology (ART), which was recently introduced into clinical
      practice. This study aimed to evaluate the effects of two vitrification systems
      Cryotop and Open Pulled Straw (OPS)-on mature oocytes gene expressions. MATERIALS
      AND METHODS: In this experimental study, the survival rate of metaphase II (MII)
      mouse oocytes were assessed after cryopreservation by vitrification via i. OPS or
      ii. Cryotop. Then we compared the fertilization rate of oocytes produced via
      these two methods. In the second experiment, we determined the effects of the two
      vitrification methods on the expression of Hspa1a, mn-Sod, and beta-actin genes
      in vitrified-warmed oocytes. Denuded MII oocytes were vitrified in two
      concentrations of vitrification solution (VS1 and VS2) by Cryotop and straw. We
      then compared the results using the two vitrification methods with fresh control
      oocytes. RESULTS: mn-Sod expression increased in the vitrified-warmed group both
      in OPS and Cryotop compared with the controls. We only detected Hspa1a in VS1 and
      control groups using Cryotop. The survival rate of the oocytes was 91.2% (VS1)
      and 89.2% (VS2) in the Cryotop groups (P=0.902) and 85.5% (VS1) and 83.6% (VS2)
      in the OPS groups (P=0.905). There were no significant differences between the
      Cryotop and the OPS groups (P=0.927). The survival rate in the Cryotop or the OPS
      groups was, nevertheless, significantly lower than the control group (P<0.001).
      The fertilization rates of the oocytes were 39% (VS1) and 34% (VS2) in the
      Cryotop groups (P=0.902) and 29 %( VS1) and 19.7% (VS2) in the OPS groups
      (P=0.413). The fertilization rates were achieved without significant differences
      among the Cryotop and OPS groups (P=0.755). CONCLUSION: Our results indicated
      that Cryotop vitrification increases both cooling and warming rates, but both
      Cryotop and OPS techniques have the same effect on the mouse oocytes after
      vitrification.

PMID- 29334210
TI  - Combined Effect of Retinoic Acid and Basic Fibroblast Growth Factor on Maturation
      of Mouse Oocyte and Subsequent Fertilization and Development.
AB  - Background: In this experimental study, germinal vesicle (GV) oocytes obtained
      from two-months-old NMRI mice were randomly divided into control, sham and three
      experimental groups. The basic culture medium was alpha-MEM supplemented with 10%
      fetal bovine serum (FBS), 50 mg/l streptomycin, 60 mg/l penicillin and 10 ng/ ml
      epidermal growth factors. Each of the experimental groups received one of the
      following treatments: RA (2 MUM), bFGF (20 ng/ml) or combination of RA and bFGF
      with the indicated concentrations. After 24 hours, capacitated spermatozoa were
      added to in vitro matured oocytes. Five hours later, the oocytes were cultured in
      fresh droplets of M2 medium for 24 hours and assessed for cleavage to the two
      cells stage. MATERIALS AND METHODS: In this experimental study, germinal vesicle
      (GV) oocytes obtained from two-months-old NMRI mice were randomly divided into
      control, sham and three experimental groups. The basic culture medium was alpha
      MEM supplemented with 10% fetal bovine serum (FBS), 50 mg/l streptomycin, 60 mg/l
      penicillin and 10 ng/ ml epidermal growth factors. Each of the experimental
      groups received one of the following treatments: RA (2 MUM), bFGF (20 ng/ml) or
      combination of RA and bFGF with the indicated concentrations. After 24 hours,
      capacitated spermatozoa were added to in vitro matured oocytes. Five hours later,
      the oocytes were cultured in fresh droplets of M2 medium for 24 hours and
      assessed for cleavage to the two-cells stage. RESULTS: As compared with the
      control group, the rate of maturation was significantly increased in the RA
      (P<0.001) and bFGF+RA (P<0.02) groups with 58 +/- 10 and 57 +/- 3.46,
      respectively. The rate of maturation was significant in the RA (P<0.02) and
      bFGF+RA (P<0.03) groups, in comparison with the bFGF group. The bFGF+RA group had
      higher rate (83 +/- 1.52) of two-cells development, than control (33 +/- 1,
      P<0.001). CONCLUSION: Our findings showed beneficial effects of 2 MUM RA and 20
      ng/ml bFGF combination on mouse oocyte IVM.

PMID- 29334211
TI  - Curcumin and Quercetin Ameliorated Cypermethrin and Deltamethrin-Induced
      Reproductive System Impairment in Male Wistar Rats by Upregulating The Activity
      of Pituitary-Gonadal Hormones and Steroidogenic Enzymes.
AB  - Background: Dietary antioxidants protect tissues and organs against
      insecticides/xenobiotic-induced damage. In the present study, we evaluated the
      results of exposure to synthetic pyrethroid insecticides, cypermethrin (Cyp) and
      deltamethrin (Del) and possible protective effects of curcumin and quercetin on
      reproductive system in male Wistar rats. MATERIALS AND METHODS: In this
      controlled experimental study, 42 male Wistar rats were randomly divided into 7
      groups of 6 animals. Group A served as control, group B was exposed to Cyp (2
      mg/kg.bw), group C was exposed to Del (2 mg/kg.bw), group D was exposed to
      Cyp+Del (2 mg/kg.bw each), group E was exposed to Cyp+Del and treated with
      curcumin (100 mg/kg.bw), group F was exposed to Cyp+Del and treated with
      quercetin (100 mg/kg.bw) and group G was exposed to Cyp+Del and treated with
      quercetin+curcumin for 45 days. RESULTS: Exposure to Cyp and Del caused decreases
      in reproductive organs weight, sperm count, sperm motility, level of sex hormones
      viz. testosterone (T), follicle stimulating hormone (FSH) and luteinizing hormone
      (LH), steroidogenic enzymes viz. 3beta-hydroxyl steroid dehydrogenase (3beta-HSD)
      and 17beta-HSD, non-enzymatic antioxidant glutathione (GSH) and enzymatic
      antioxidants viz. superoxide dismutase (SOD), catalase (CAT), glutathione
      peroxidase (GPx), glutathione-S-transferase (GST) and glutathione reductase (GR)
      activity and increases in sperm abnormalities and lipid peroxidation (LPO). The
      exposure also adversely affected the histo-achitecture of testes. Single and
      combined treatment with curcumin and quercetin significantly ameliorated Cyp and
      Del-induced damage in reproductive system. CONCLUSION: Curcumin and quercetin
      protected against Cyp and Del-induced reproductive system toxicity and oxidative
      damage in rats. The increases in activities of 3beta-HSD and 17beta-HSD with
      concomitant increases in testosterone were mainly responsible for ameliorating
      effects of curcumin and quercetin. Curcumin showed slightly better activity as
      compared to quercetin. The combination of both antioxidants offered more
      protection compared to each one alone.

PMID- 29334212
TI  - Comparison of The Efficacy and Safety of Palomo, Ivanissevich and Laparoscopic
      Varicocelectomy in Iranian Infertile Men with Palpable Varicocele.
AB  - Background: This study aimed to compare the effects of three commonly used
      varicocelectomy techniques namely, open retroperitoneal ligation (Palomo), open
      inguinal ligation (Ivanissevich) and laparoscopy, in Iranian infertile men.
      MATERIALS AND METHODS: This retrospective study was conducted on 70 infertile men
      with palpable varicocele who underwent one of the varicocelectomy techniques
      namely, Palomo, Ivanissevich, or laparoscopy. Basic information about semen
      parameters were collected and registered prior to the surgery. Three months after
      the surgery, semen parameters and surgical complications were investigated in all
      patients. RESULTS: The Palomo technique was significantly associated with fewer
      complications compared to other techniques (P=0.006). The means of sperm
      concentration, normal motility and normal morphology were significantly different
      among the three groups after surgery (P=0.025, 0.023 and 0.047, respectively).
      However, after adjustment for potential confounders, in addition to the baseline
      values of semen parameters, significant differences were observed only in sperm
      concentration among the groups (P=0.040). CONCLUSION: Varicocelectomy improved
      sperm parameters. The Ivanissevich technique was more effective in improving
      sperm concentration compared to the laparoscopic method. The lowest rates of
      complications were related to the Palomo technique.

PMID- 29334213
TI  - Conservative Management of Ovarian Fibroma in A Case of Gorlin-Goltz Syndrome
      Comorbid with Endometriosis.
AB  - Ovarian fibromas are the most common benign solid ovarian tumors, which are often
      difficult to diagnose preoperatively. Ovarian fibromas, especially in bilateral
      cases, may be cases of Gorlin-Goltz syndrome (GGS), a rare autosomal dominant
      disorder with predisposition to basal cell carcinomas (BCCs) and other various
      benign and malignant tumors. This case report describes a 25 year-old female with
      GGS, bilateral ovarian fibroma, endometriosis and septated uterus, which was
      referred to the Gynecology Clinic of Rasoul-e-Akram Hospital in October 2016.
      This patient had facial asymmetry due to recurrent odontogenic keratocysts. In
      young cases of ovarian fibromas as reported here, conservative surgical
      management can preserve ovarian function and fertility. These patients must be
      followed up by a multidisciplinary team and submitted to periodic tests.

PMID- 29334214
TI  - Quality of Life and Its Influencing Factors of Couples Referred to An Infertility
      Center in Shiraz, Iran.
AB  - In this article which was published in Int J Fertil Steril, Vol 11, No 4, Jan-Mar
      2018, on pages 293-297, the "Duration of tducation (male)" was misspelled in
      Table 1. The corrected one is "Duration of education (male)". In the sentence
      "These differences might be related to the use of a fertility-specific instrument
      (FertiQoL) in the study by Huppelschoten et al. (23) and the current study
      compared to the general QoL assessment instrument by Chachamovich et al. (24) and
      Rashidi et al. (15)." Which was at the page of 296 in the discussion section, the
      word "generic" was corrected in to "general".

PMID- 29334215
TI  - A year in review in Minerva Anestesiologica 2017 Critical Care: experimental and
      clinical studies.

PMID- 29334216
TI  - Lysosome-Independent Intracellular Drug/Gene Codelivery by Lipoprotein-Derived
      Nanovector for Synergistic Apoptosis-Inducing Cancer-Targeted Therapy.
AB  - In this paper, reconstituted high-density lipoprotein (rHDL), a lipoprotein
      derived nanovector, was constructed for codelivery of paclitaxel (PTX) and wild
      type p53 gene (p53). The particle size and the zeta potential of PTX-DODAB/p53
      rHDL nanoparticles were 177.2 nm and -20.06 mV, respectively. Meanwhile, they
      exhibited great serum stability and satisfactory sustained release
      characteristics in vitro. PTX-DODAB/pDNA-rHDL nanoparticles simultaneously
      improved the cellular uptake of PTX and pDNA via scavenger receptor B type I (SR
      BI) mediated lysosome-independent internalization and promoted the transfection
      of pDNA in MCF-7 cells, which were revealed by flow cytometry and confocal laser
      scanning microscopy analyses. The high p53 protein expression in MCF-7 cells
      after rHDL-mediated transfection was detected by Western blotting assay.
      Moreover, PTX-DODAB/p53-rHDL nanoparticles showed superior cytotoxicity and
      significantly induced apoptosis in SR-BI overexpressed MCF-7 cells. In in vivo
      studies, PTX-DODAB/p53-rHDL nanoparticles without obvious toxic effects to
      vessels, blood, or major organs exhibited efficient tumor targeting and
      encouraging antitumor effects on tumor-bearing nude mice compared with controls.
      All the results above indicated that PTX-DODAB/p53-rHDL nanoparticles held broad
      prospects in combination of chemotherapeutics and gene therapeutic agents for
      cancer-targeted therapy.

PMID- 29334218
TI  - Photochemically Induced Intramolecular Radical Cyclization Reactions with Imines.
AB  - The photochemically induced intramolecular hydrogen abstraction or hydrogen atom
      transfer in cyclic imines 8a,b followed by a cyclization is investigated. Two
      types of products are observed, one resulting from the formation of a C-C bond,
      the other from the formation of a C-N bond. A computational study reveals that
      hydrogen is exclusively transferred to the imine nitrogen leading to a triplet
      diradical intermediate. After intersystem crossing, the resulting zwitterionic
      intermediate undergoes cyclization leading to the final product.

PMID- 29334217
TI  - Characterization of an Hsp90-Independent Interaction between Co-Chaperone p23 and
      Transcription Factor p53.
AB  - Cancer-suppressing transcription factor p53 is regulated by a wide variety of
      cellular factors, including many chaperones. The DNA-binding domain (DBD) of p53
      is known to interact with the chaperone Hsp90, but the role of other members of
      the chaperone network, including co-chaperones such as p23, is unknown. Using a
      combination of nuclear magnetic resonance (NMR) titration, isothermal titration
      calorimetry, fluorescence anisotropy, and native agarose gel electrophoresis, we
      have identified a direct interaction between the p53 DBD and Hsp90 co-chaperone
      p23 that occurs in the absence of Hsp90. The affinity is relatively weak and
      largely determined by electrostatic interactions between the acidic C-terminal
      disordered tail of p23 and the two DNA-binding regions of the p53 DBD. We show by
      NMR and native agarose gel electrophoresis that a p53-specific double-stranded
      DNA sequence competes successfully with p23 for binding to the p53 DBD. The Hsp90
      independence of the interaction between p23 and p53 DBD, together with the
      competition of p23 versus DNA for p53, raises the intriguing possibility that
      p23, like other small charged proteins, may affect p53 in hitherto unknown ways.

PMID- 29334219
TI  - Mussel-Inspired Conductive Polymer Binder for Si-Alloy Anode in Lithium-Ion
      Batteries.
AB  - The excessive volume changes during cell cycling of Si-based anode in lithium ion
      batteries impeded its application. One major reason for the cell failure is
      particle isolation during volume shrinkage in delithiation process, which makes
      strong adhesion between polymer binder and anode active material particles a
      highly desirable property. Here, a biomimetic side-chain conductive polymer
      incorporating catechol, a key adhesive component of the mussel holdfast protein,
      was synthesized. Atomic force microscopy-based single-molecule force measurements
      of mussel-inspired conductive polymer binder contacting a silica surface revealed
      a similar adhesion toward substrate when compared with an effective Si anode
      binder, homo-poly(acrylic acid), with the added benefit of being electronically
      conductive. Electrochemical experiments showed a very stable cycling of Si-alloy
      anodes realized via this biomimetic conducting polymer binder, leading to a high
      loading Si anode with a good rate performance. We attribute the ability of the Si
      based anode to tolerate the volume changes during cycling to the excellent
      mechanical integrity afforded by the strong interfacial adhesion of the
      biomimetic conducting polymer.

PMID- 29334220
TI  - Computational Design, Synthesis, and Structure Property Evaluation of 1,3
      Thiazole-Based Color-Tunable Multi-heterocyclic Small Organic Fluorophores as
      Multifunctional Molecular Materials.
AB  - Probing the chemical space of luminescent organic materials built on novel cores
      is highly imperative for its potential to expand the horizons of advanced
      functional materials. Small organic fluorophores possessing therapeutic traits
      can contribute to theranostics. We coupled computational and classical synthetic
      chemistry strategies for the rational design of 5-(hetero-2-yl)-1,3-thiazoles as
      color-tunable fluorophore core. With the aid of DFT and TD-DFT, we prove that the
      multi-heterocyclic system is built on a thiazole-het core with three inherent
      tunable sites on thiazole (C2, C4, and C5) capable of accommodating a panoply of
      substituents as a multifunctional molecular materials' platform. This de novo
      design offered unprecedented freedom to control strength and direction of charge
      transfer by varying donor-acceptor fragments. A 30-member fluorophore library
      built on thiazole-thiophene/furan core was accomplished using commercial reagents
      by a simple [4 + 1] synthesis. Structure-photophysical property studies revealed
      large Stokes shift, positive solvatochromism, acidochromism, and color tunability
      in different solvents and were rationalized using computational calculations. In
      vitro studies indicated 1a to be active against HL-60 cell lines, suggesting the
      possibility of expanding the core for theranostics. The lower values of computed
      hole reorganization energies indicated their potential as hole transporting
      materials in optoelectronics and widen the scope of these molecules as advanced
      functional materials.

PMID- 29334222
TI  - Online Preconcentration in Capillaries by Multiple Large-Volume Sample Stacking:
      An Alternative to Immunoassays for Quantification of Amyloid Beta Peptides
      Biomarkers in Cerebrospinal Fluid.
AB  - A novel electrokinetic preconcentration approach, so-called multiple pressure
      assisted large-volume sample stacking with an electroosmotic flow pump (M-PA
      LVSEP), was developed to allow in-capillary enrichment and separation of analytes
      from unlimited sample volumes. With this approach, the inherent limitation of in
      capillary electrokinetic preconcentrations to the separation capillary volume can
      be overcome. The M-PA-LVSEP protocol relies on repeated cycles of pressure
      assisted electroosmotic pumping and injection of extremely large sample volumes
      for analyte stacking and sample matrix removal. This technique was developed to
      address the challenge of sensitive and simultaneous determination of several
      amyloid beta (Abeta) peptides, which are biomarkers for the molecular diagnosis
      of Alzheimer's disease (AD). For the first time, reliable quantification of
      different species of fluorescently derivatized Abeta peptides, that is, Abeta 1
      42, Abeta 1-40, and Abeta 1-38 down to subnanomolar ranges in cerebrospinal
      fluids (CSF) from AD and non-demented patients (healthy controls) was made
      possible without recourse to immunoassay, immunoprecipitation, or mass
      spectrometry approaches. Based on the stacking from a sample plug representing up
      to 400% of the total capillary volume, sensitive enhancement factors up to 170
      could be achieved with this "antibody free" approach. Quantification limits for
      these Abeta peptides down to 0.05 nM with capillary electrophoresis coupled with
      laser-induced fluorescent detection could be obtained. Excellent agreement
      between results from M-PA-LVSEP and the gold standard ELISA method was achieved
      for measurements of Abeta 1-42 in CSF, with a determination correlation (r2)
      better than 0.993.

PMID- 29334221
TI  - Extracellular Enzyme Composition and Functional Characteristics of Aspergillus
      niger An-76 Induced by Food Processing Byproducts and Based on Integrated
      Functional Omics.
AB  - Byproducts of food processing can be utilized for the production of high-value
      added enzyme cocktails. In this study, we utilized integrated functional omics
      technology to analyze composition and functional characteristics of extracellular
      enzymes produced by Aspergillus niger grown on food processing byproducts. The
      results showed that oligosaccharides constituted by arabinose, xylose, and
      glucose in wheat bran were able to efficiently induce the production of
      extracellular enzymes of A. niger. Compared with other substrates, wheat bran was
      more effective at inducing the secretion of beta-glucosidases from GH1 and GH3
      families, as well as >50% of proteases from A1-family aspartic proteases.
      Compared with proteins induced by single wheat bran or soybean dregs, the protein
      yield induced by their mixture was doubled, and the time required to reach peak
      enzyme activity was shortened by 25%. This study provided a technical platform
      for the complex formulation of various substrates and functional analysis of
      extracellular enzymes.

PMID- 29334223
TI  - A Novel Color Modulation Analysis Strategy through Tunable Multiband Laser for
      Nanoparticle Identification and Evaluation.
AB  - Creating color difference and improving the color resolution in digital imaging
      is crucial for better application of color analysis. Herein, a novel color
      modulation analysis strategy was developed by using a homemade tunable multiband
      laser illumination device, in which the portions of R, G, and B components of the
      illumination light are discretionarily adjustable, and hence the sample color
      could be visually modulated continuously in the RGB color space. Through this
      strategy, the color appearance of single gold nanorods (AuNRs) under dark-field
      microscopy was migrated from the spectrally insensitive red region to the
      spectrally sensitive green-yellow region. Unlike the traditional continuous-wave
      light source illumination, wherein the small spectral variations in the samples
      within a narrow spectral range are averaged by the whole spectrum of the light
      source, leading to little color difference, the application of sharp, multiband
      laser illumination could enlarge the color separation between samples, thus
      resulting in high spectral sensitivity in color analysis. By comparing the
      corresponding color evolution processes of different samples as the multiband
      combination of the laser illumination was changed, more efficient color
      separation of AuNRs was achieved. With this instrument and single Ag@AuNRs as the
      sulfide probe, we achieved high throughput and highly sensitive detection of
      sulfide at a detection limit of 0.1 nM, a more than 2 orders of magnitude
      improvement compared to the previous color sensing scheme. This strategy could be
      utilized for nanoparticle identification, evaluation, and determination in
      biological imaging and biochemical analysis.

PMID- 29334224
TI  - Diversity-Oriented Approach to N-Heterocyclic Compounds from alpha-Phenyl-beta
      enamino Ester via a Mitsunobu-Michael Reaction Sequence.
AB  - Herein we delineate a novel route for the diastereoselective construction of
      diversely substituted N-heterocyclic ring systems as valuable scaffolds for
      natural products and pharmaceuticals, starting from an easily accessible
      prochiral alpha-phenyl-beta-enamino ester. The reaction sequence relies on the
      unexplored reactivity of alpha-phenyl-beta-enamino ester as a nucleophilic
      partner in the Mitsunobu reaction to forge the N-tethered alkene
      alcohol/thiol/amine intermediate, which was subjected to an intramolecular hetero
      Michael addition reaction under mild conditions to furnish the respective N
      heterocyclic compounds embedded with an exocyclic chiral center in high yields
      and excellent diastereoselectivities. The methodology is amenable for a broad
      range of substrates based on a metal-free approach.

PMID- 29334225
TI  - Fate of Poly(3-octylthiophene) Transducer in Solid Contact Ion-Selective
      Electrodes.
AB  - An experimental approach allowing visualization and quantification of the
      underestimated spontaneous process of partition of conducting polymer transducer
      material to the ion-selective membrane phase is proposed. The approach proposed
      is based on optical properties of the transducer material applied, using
      polythiophene as a model system. It is shown that this process occurs not only
      during the sensor preparation step but also during pretreatment of the sensor
      before use. As shown, this uncontrolled partition of the transducer to the
      receptor leads to conducting polymer contents in the membrane phase reaching 0.5%
      w/w; this process is accompanied by a partial spontaneous change of the oxidation
      state of polythiophene. The conducting polymer present in the membrane
      participates to some extent in the overall response of the sensor, which can be
      observed as a change in the polythiophene optical emission spectra. Fluorescence
      microscopic images obtained clearly show that the conducting polymer is
      distributed throughout the membrane thickness, being present also at the
      membrane/solution interface. The experimental results presented were obtained for
      K+-selective sensors using poly(3-octylthiophene) as a model transducer; however,
      the proposed approach is also applicable for other systems.

PMID- 29334226
TI  - Ethnic youth and sexual identity: the role of clinical and social support for
      'double minorities'.
AB  - OBJECTIVES: Sexual-minority youth exhibit increased rates of psychiatric
      morbidity, subject to various social factors. We examine the impact of ethnicity
      and culture on these phenomena, with particular reference to Asian youth living
      in Western societies. CONCLUSIONS: Youth from minority ethnic groups who do not
      identify with their native gender and/or who are not exclusively heterosexual are
      known as 'double minorities'. Available evidence suggests that such individuals
      are at particularly increased risk of depression and suicide, but that this may
      be mitigated by social support. More research is needed to understand the
      challenges faced by 'double minorities', notably their perception of and ability
      to access available clinical and social supports.

PMID- 29334227
TI  - Using a television documentary to prevent suicide in men and boys.
AB  - OBJECTIVES: We investigated whether a documentary about masculinity and
      suicidality ( Man Up) could raise males' awareness of societal pressures to
      conform to masculine norms and influence their likelihood of connecting with
      their male friends and seeking help. METHODS: We conducted a repeat cross
      sectional survey, posting versions of the survey online before and after Man Up
      was screened. RESULTS: 1287 male respondents completed the survey; 476 completed
      the pre-screening survey, 811 the post-screening survey (192 had not viewed Man
      Up, 619 had). Those who had viewed Man Up were more likely to desire closer
      relationships with their male friends than those who had not, and had greater
      awareness of societal pressures on males, but were no more likely to seek help.
      Almost all respondents who saw Man Up indicated they would recommend it to
      others, and most said it changed the way they thought about the term 'man up'.
      They indicated they would be likely to undertake a number of adaptive actions
      following the show, and provided overwhelmingly positive feedback. CONCLUSIONS:
      Man Up appeared to effectively address factors that place males at heightened
      risk of suicide.

PMID- 29334228
TI  - Use of ECT in the presence of acute bilateral posterior vitreous detachmanet.
AB  - OBJECTIVES: We describe a case of acute bilateral posterior vitreous detachment
      (PVD) in a 71-year-old female, which developed during a course of
      electroconvulsive therapy (ECT) for treatment-resistant depression. The risks and
      benefits of continuing ECT were assessed and the patient completed the full
      course of 16 ECT treatments without further ophthalmic complications.
      CONCLUSIONS: As the incidence of PVD increases with age, and ECT is used more
      frequently in elderly people with depression, we recommend paying attention to
      ophthalmic symptoms as part of the routine clinical monitoring of ECT side
      effects. If ophthalmic symptoms occur, the risks and benefits of ECT need to be
      weighed up including consultation with an ophthalmologist.

PMID- 29334229
TI  - Physical and psychological health of carers of young people with first episode
      psychosis.
AB  - OBJECTIVE: Carers of people with psychosis may experience psychological distress
      and caregiving burden. However, few studies have examined both psychological and
      physical health of carers of young people with first episode psychosis (FEP).
      METHOD: A total of 32 young people with FEP and 42 of their carers were recruited
      from a mental health service. Standardised scales were administered to assess
      carers' psychological distress and risk for development of Type 2 diabetes. Their
      body mass index, waist circumference and blood pressure were measured. RESULTS: A
      total of 24% ( n = 10) of carers experienced high/very high psychological
      distress and 39.0% ( n = 16) had high risk for Type 2 diabetes. It was common for
      carers to be overweight ( n = 33, 78.6%) and to have hypertension ( n = 14,
      33.3%). Carers' higher levels of psychological distress were associated with
      shorter duration of illness in the young person. CONCLUSIONS: Caring for a young
      person with FEP is associated with poor physical and psychological health.
      Findings show the importance of supporting carers' physical and psychological
      health early in treatment of young people with FEP.

PMID- 29334230
TI  - DNA methylation changes and evolution of RNA-based duplication in Sus scrofa:
      based on a two-step strategy.
AB  - AIM: This study aims to couple DNA methylation changes and evolution of
      retrogenes. MATERIALS & METHODS: A new two-step strategy was developed to screen
      retrogenes. Further, reduced representation bisulfite sequencing and RNA-seq data
      of eight tissues were used to analyze retrogenes. RESULTS: A total of 964
      retrocopies were identified and new retrocopies were available for the synthesis
      of glycans and lipids corresponding to pig phenotypic traits. Retrogenes were
      consistently hypermethylated. Hypomethylation of parental genes presented more
      susceptibility to retroposition. Promoter DNA methylation of retrogenes was
      negatively correlated with evolutionary time and played important roles in
      regulating retrogene tissue-specific expression pattern. CONCLUSION: A two-step
      procedure is effective and necessary for identifying retrogenes. DNA methylation
      drives origination, survival, evolution and expression of retrogenes.

PMID- 29334231
TI  - Social capital and PTSD among PLWHA in China: the mediating role of resilience
      and internalized stigma.
AB  - Post-traumatic Stress Disorder (PTSD) is frequent among people living with
      HIV/AIDS (PLWHA). Few studies have investigated social-psychological predictors
      of PTSD in China. This study aimed to examine relationships between social
      capital, stigma, resilience and PTSD among PLWHA in China, and to provide
      effective suggestions for PTSD intervention. A cross-sectional study of 520 PLWHA
      was conducted from November 2015 to January 2016. Survey data were collected
      using anonymous self-reported questionnaire. Multivariable analyses were used to
      examine related factors of PTSD, and causal mediation analyses were conducted to
      assess whether stigma and resilience were mediators. Results indicated that
      higher risk of PTSD was independent associated with stronger stigma, decreasing
      social capital and lower resilience. There was an indirect relationship of social
      capital on PTSD mediated through resilience and HIV-related stigma. Therefore,
      PTSD intervention programs should not only pay attention to the role of social
      capital on PTSD, but also attach importance to stigma and resilience on PTSD
      symptoms.

PMID- 29334232
TI  - Stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma: imaging
      evaluation post treatment.
AB  - Surgical resection, when feasible, is the standard of care for hepatocellular
      carcinoma. However, many tumours are not resectable at the time of diagnosis.
      Recently, stereotactic body radiation therapy (SBRT) has emerged as a non
      invasive local therapy for both non-resectable primary hepatic malignancies as
      well as hepatic metastases. Knowledge of the expected hepatic parenchymal
      appearance post treatment, as well as potential pitfalls and complications, is
      essential for accurate evaluation of treatment response. This pictorial review
      provides a fundamental description of the SBRT technique, outlines the expected
      cross-sectional imaging appearances of tumour response, and highlights potential
      pitfalls in interpretation. The expected liver parenchymal changes post-SBRT are
      also reviewed, along with some common radiation-induced complications.

PMID- 29334233
TI  - Perceived discrimination and mental health among older African Americans: the
      role of psychological well-being.
AB  - OBJECTIVES: Examine the effect of perceived discrimination (both racial and non
      racial) on the mental health of older African Americans and explore the buffering
      role of psychological well-being (purpose in life and self-acceptance). METHODS:
      Using an older African American subsample from the National Health Measurement
      Study (n = 397), multiple regression model by gender was used to estimate the
      effects of two types of discrimination (every day and lifetime) on SF-36 mental
      component and mediating role of two concepts of psychological well-being.
      RESULTS: With no gender difference on the everyday discrimination, older men
      experienced more lifetime discrimination than older women. The older men's model
      found that the depressive symptomology was significantly explained by only
      everyday discrimination and mediated by self-acceptance. The older women's model
      was significant, with everyday discrimination and both self-acceptance and
      purpose in life emerging as mediating variables. DISCUSSION: The prevalence of
      institutional lifetime discrimination for older African American men is
      consistent with previous research. Inconsistency with past research indicated
      that only everyday discrimination is statistically associated with depressive
      symptoms. Considering the buffering role of psychological well-being served for
      mental health problems, practitioners need to emphasize these factors when
      providing services to older African Americans. Equally important, they must
      address racial discrimination in mental health care settings.

PMID- 29334234
TI  - Is there an association between severity of illness and psychiatric symptoms in
      patients with chronic renal failure?
AB  - Chronic renal failure (CRF) is a frequent condition in elderly subjects, and it
      is associated with psychiatric comorbidity, especially depressive symptoms.
      Purpose of the present research was to compare patients with different severity
      of chronic kidney disease (CKD) in terms of psychiatric symptoms. One hundred CKD
      subjects were randomly selected among those attending the Department of
      Nephrology, University of Milan. The patients were evaluated through the
      following rating scales: Mini-Mental State Examination (MMSE), Beck Depression
      Inventory (BDI), Symptom Checklist (SCL-90), Kidney Disease Quality of Life-
      Short Form (KDQOL-SF) and Cumulative Illness Rating Scale (CIRS). A multivariable
      linear regression analysis was performed considering eGFR as continuous-dependent
      variable and rating scale scores as independent variables. A worse eGFR
      significantly correlated with the score about the effects of kidney disease on
      daily life (r = 0.25, p = 0.01) and the burden of kidney disease (r = 0.18, p =
      0.05). Statistical significance of kidney disease on daily life persisted also in
      the final multivariate model (t = 2.04, p = 0.04). Severity of renal dysfunction
      seems to influence few psychiatric outcomes, particularly those related to
      quality of life and daily functioning. This result might depend on the over
      worrying derived from the necessity to start a renal replacement therapy in the
      near future.

PMID- 29334235
TI  - Impact of an assertive community treatment model of care on the treatment of
      prisoners with a serious mental illness.
AB  - OBJECTIVES: This study aims to describe the impact of a mental health assertive
      community treatment prison model of care (PMOC) on improving the ability to
      identify prisoner needs, provide interventions and monitor their efficacy.
      METHODS: We carried out a file review across five prisons of referrals in the
      year before the implementation of the PMOC in 2010 ( n = 423) compared with
      referrals in the year after ( n = 477). RESULTS: Some improvements in the
      identification of needs and providing interventions were detected. There was
      increased use of medication management and clinically significant improvement in
      addressing engagement with families. Monthly multi-disciplinary team face-to-face
      contact improved. CONCLUSIONS: Meeting the needs of mentally ill prisoners is
      challenged by the complexity of the custodial environment. Improvements made
      resulted from changing the model of care, rather than adding new resources.

PMID- 29334236
TI  - Whole Body MRI and oncology: recent major advances.
AB  - MRI is a very attractive approach for tumour detection and oncological staging
      with its absence of ionizing radiation, high soft tissue contrast and spatial
      resolution. Less than 10 years ago the use of Whole Body MRI (WB-MRI) protocols
      was uncommon due to many limitations, such as the forbidding acquisition times
      and limited availability. This decade has marked substantial progress in WB-MRI
      protocols. This very promising technique is rapidly arising from the research
      world and is becoming a commonly used examination for tumour detection due to
      recent technological developments and validation of WB-MRI by multiple studies
      and consensus papers. As a result, WB-MRI is progressively proposed by
      radiologists as an efficient examination for an expanding range of indications.
      As the spectrum of its uses becomes wider, radiologists will soon be confronted
      with the challenges of this technique and be urged to be trained in order to
      accurately read and report these examinations. The aim of this review is to
      summarize the validated indications of WB-MRI and present an overview of its most
      recent advances. This paper will briefly discuss how this examination is
      performed and which are the recommended sequences along with the future
      perspectives in the field.

PMID- 29334237
TI  - Safety of working patterns among UK neuroradiologists: what can we learn from the
      aviation industry and cognitive science?
AB  - As the volume and complexity of imaging in the UK continues to rise, there is
      pressure on radiologists to spend increasing lengths of time reporting to cope
      with the growing workload. However, there is limited guidance for radiologists
      about structuring the working day to strike the necessary balance between
      achieving satisfactory reporting volume and maintaining quality and safety. We
      surveyed 86 neuroradiologists (receiving 59 responses), regarding time spent
      reporting, frequency and duration of work breaks, and break activities. Our
      results demonstrate that some neuroradiologists report for up to 12 h a day and
      for 4 h before taking a break. Mean duration of breaks is less than 15 min and
      these often consist of computer screen-based or cognitively demanding tasks. Many
      areas of medicine have looked to the aviation industry to develop improvements in
      safety through regulated, standardised practices. There are parallels between the
      work of air traffic controllers (ATCs) and radiologists. We review the
      legislation that controls the working hours of UK ATCs to minimise fatigue
      related errors, and its scientific basis. We also consider the vigilance
      decrement, a concept in cognitive science which describes the reduction in
      performance with increasing time-on-task. We conclude that, in comparison with
      ATCs, work patterns among radiologists are poorly standardised and potentially
      dangerous. Evidence suggests that placing limits on reporting time and minimum
      break duration, as well as ensuring appropriate break activities, can benefit
      reporting quality. It is imperative that radiologists and managers heed these
      lessons, to improve standards and protect patients from error.

PMID- 29334238
TI  - Chemical constituents from the flowers of Satsuma mandarin and their free radical
      scavenging and alpha-glucosidase inhibitory activities.
AB  - Flowers of Citrus plants are used as mild sedatives and for the treatment of
      insomnia in traditional medicines. In Japan, tea made from the flowers of Satsuma
      mandarin is consumed as healthy drink. Hesperidin (1), hesperetin (2), rutin (3),
      quercetin (4), nicotiflorin (5), eriocitrin (6), narirutin (7), phenylethyl
      glucoside (8) and unshuoside A (9) were isolated from the MeOH extract of fresh
      flowers. Structure elucidation of these compounds was performed on the basis of
      NMR spectroscopic data. Among them, rutin (3), quercetin (4) and eriocitrin (6)
      showed potent free radical scavenging activity, whereas hesperetin (2) and
      quercetin (4) showed potent alpha-glucosidase inhibitory activity.

PMID- 29334239
TI  - Antimicrobial and antiquorum-sensing activity of Ricinus communis extracts and
      ricinine derivatives.
AB  - Ricinine (1), a known major alkaloid in Ricinus communis plant, was used as a
      starting compound for the synthesis of six ricinine derivatives; two new and four
      known compounds. The new derivatives; 3-amino-5-methyl-1H-pyrazolo[4,3-c]pyridin
      4(5H)-one (2), and 3-amino-5-methyl-1-(phenylsulfonyl)-1H-pyrazolo[4,3-c]pyridin
      4(5H)-one (3), as well as the previously prepared derivatives (4-7) were
      subjected for antimicrobial and antiquorum-sensing evaluation in comparison to
      different R. communis extracts. Acetyl ricininic acid derivative (5) showed the
      highest antimicrobial activity among all tested derivatives against
      Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Pseudomonas
      aeuroginosa and Candida albicans. However, compound 7 (4-methoxy-1-methyl-2-oxo
      1,2-dihydropyridine-3-carboxamide) showed the highest antiquorum-sensing activity
      among all tested compounds and extracts. These findings proved the usefulness of
      ricinine as a good scaffold for the synthesis of new antimicrobial and antiquorum
      sensing derivatives in spite of its poor contribution to the antimicrobial
      activity of the plant extracts.

PMID- 29334240
TI  - New method for estimating arterial pulse wave velocity at single site.
AB  - The clinical importance of measuring local pulse wave velocity (PWV), has
      encouraged researchers to develop several local methods to estimate it. In this
      work, we proposed a new method, the sum-of-squares method [Formula: see text],
      that allows the estimations of PWV by using simultaneous measurements of blood
      pressure (P) and arterial diameter (D) at single-location. Pulse waveforms
      generated by: (1) two-dimensional (2D) fluid-structure interaction simulation
      (FSI) in a compliant tube, (2) one-dimensional (1D) model of 55 larger human
      systemic arteries and (3) experimental data were used to validate the new formula
      and evaluate several classical methods. The performance of the proposed method
      was assessed by comparing its results to theoretical PWV calculated from the
      parameters of the model and/or to PWV estimated by several classical methods. It
      was found that values of PWV obtained by the developed method [Formula: see text]
      are in good agreement with theoretical ones and with those calculated by PA-loop
      and D2P-loop. The difference between the PWV calculated by [Formula: see text]
      and PA-loop does not exceed 1% when data from simulations are used, 3% when in
      vitro data are used and 5% when in vivo data are used. In addition, this study
      suggests that estimated PWV from arterial pressure and diameter waveforms provide
      correct values while methods that require flow rate (Q) and velocity (U)
      overestimate or underestimate PWV.

PMID- 29334241
TI  - Transcriptional regulation on the gene expression signature in combined allergic
      rhinitis and asthma syndrome.
AB  - AIM: This study was intended to evaluate transcriptional regulation of gene
      expression signatures in combined allergic rhinitis and asthma syndrome (CARAS).
      MATERIALS & METHODS: The blood samples of three patients with CARAS, three
      patients with allergic rhinitis and three normal controls were obtained. The
      cuffdiff, miRDeep2 and DEGseq were used to quantify the expression of genes and
      miRNAs, respectively. And p-value < 0.01 and false discovery rate < 0.001 were
      considered as significant differences of genes and miRNAs, respectively. Gene
      ontology and the Kyoto Encyclopedia of Genes and Genomes were used to analyze the
      biological function. And the cut-off value for significance was p < 0.05.
      RESULTS: SLC14A1, SNCA, TNS1, KAT2B and PARP1 were regulated by hsa-miR-93-5p,
      hsa-miR-92a-3p and hsa-miR-21-5p. Additionally, phagosome (p =
      0.00627769839083361) was the only significantly enriched signal pathway involving
      HLA-DOA, TUBB2A and MRC2. CONCLUSION: Disordered expression of genes under the
      regulation of miRNAs may play an important role in CARAS.

PMID- 29334242
TI  - Development and disease in a dish: the epigenetics of neurodevelopmental
      disorders.
AB  - Human neurodevelopmental disorders (NDDs) involve mutations in hundreds of
      individual genes, with over-representation in genes encoding proteins that alter
      chromatin structure to modulate gene expression. Here, we highlight efforts to
      model these NDDs through in vitro differentiation of patient-specific induced
      pluripotent stem cells into neurons. We discuss how epigenetic regulation
      controls normal cortical development, how mutations in several classes of
      epigenetic regulators contribute to NDDs, and approaches for modeling cortical
      development and function using both directed differentiation and formation of
      cerebral organoids. We explore successful applications of these models to study
      both syndromic and nonsyndromic NDDs and to define convergent mechanisms,
      addressing both the potential and challenges of using this approach to define
      cellular and molecular mechanisms that underlie NDDs.

PMID- 29334243
TI  - Facile synthesis of simple 2-oxindole-based compounds with promising
      antiproliferative activity.
AB  - AIM: Discovery of novel potent anticancer agents with lower side effects is a
      challenge to overcome cancer, the second leading cause of death. METHODOLOGY: 2
      oxindole-based hydrazides (6a-g) and benzenesulfonyl hydrazides (9a-d) were
      synthesized by simple condensation reactions of the appropriate hydrazides (2a-g)
      or (8a-d) with 1-ethyl-2,3-oxindolinedione (4). They were screened for their
      cytotoxicity against HepG2 (liver), MCF-7 (breast), HCT116 (colon) and A549
      (lung) cancer cell lines. RESULTS: The substituted benzohydrazides (6b-g)
      revealed higher activity and selectivity toward the tested cell lines than
      doxorubicin and 9a-d. Compound 6c exhibited the highest activity against MCF-7
      cell line with IC50 = 0.0058 MUM and it induced apoptosis by caspase-3
      activation, Bax upregulation and Bcl-2 downregulation in a dose-dependent manner.
      CONCLUSION: This compound can be considered as a potent cytotoxic agent with
      apoptotic induction property.

PMID- 29334244
TI  - Evolving concepts and use of immunohistochemical biomarkers in flat non
      neoplastic urothelial lesions: WHO 2016 classification update with diagnostic
      algorithm.
AB  - CONTEXT: The classification of flat non-neoplastic urothelial lesions has been
      evolved through the years in the attempt to better define a spectrum of
      morphologic entities with somewhat overlapping features. Differentiating these
      lesions is important because of differences in patient management and clinical
      outcome. Materials and methods and objective: A systematic review of the
      literature has been carried out in order to (1) assess the most striking clinical
      features of each lesion and (2) identify those morphological traits and
      immunophenotypical markers which may aid in the differential diagnosis. RESULTS
      AND CONCLUSION: Our results point out the importance of a proper definition of
      flat non-neoplastic urothelial lesions in order to predict clinical behaviour and
      allow tailored patient management; therefore, we attempted to construct a novel
      and "easy to use" algorithm for a clear, standardized and evidence-based
      pathological diagnosis.

PMID- 29334245
TI  - Steroids from herbs of Reineckia carnea and their anticomplement activities.
AB  - A new polyhydroxylated pregnane, named lbeta,2beta,3beta,4beta,5beta,6beta
      hexolhydroxy-pregn-16-en-20-one (1), along with nine known (2-10) steroidal
      saponins were isolated from the whole plant of Reineckia carnea. Structure
      elucidations of all compounds were established by interpretation of their NMR
      spectral data, HR-ESI-MS and comparing with literatures. In addition, these
      compounds were evaluated with anticomplement activity. The result showed that
      compound 1 exhibited anticomplement effects with the CH50 values of 0.043 mg/mL,
      but saponins (2-10) showed no inhibition. Interestingly, hydrolysis of steroidal
      saponins (2-10) resulted in its aglycones (2a-10a) correspondingly which showed
      anticomplement activity with the CH50 values of 0.049-0.156 mg/mL.

PMID- 29334246
TI  - Screening of north-east Mexico medicinal plants with activities against herpes
      simplex virus and human cancer cell line.
AB  - The plants examined in this study have previous biological activity reports
      indicating the possibility of found activity against herpes and cancer cell. The
      aim of this contribution was to carry out a screening of Juglans mollis
      (Juglandaceae), Persea americana (Lauraceae), Hamelia patens (Rubiaceae), Salvia
      texana (Lamiaceae), Salvia ballotaeflora (Lamiaceae), Ceanothus coeruleus
      (Rhamnaceae), Chrysactinia mexicana (Asteraceae) y Clematis drummondii
      (Ranunculaceae), against HeLa cells, VHS-1 and VHS-2. The method MTT was used to
      determine the 50% cytotoxic concentration (CC50), in Vero and HeLa cell lines. To
      determine the 50% inhibitory concentration (IC50) against herpes, the plaque
      reduction method was used. Results showed that none of the plants exhibited
      activity against HeLa cells. About antiherpetic activity, J. mollis and S.
      ballotaeflora extracts present antiherpetic activity in terms of their SI,
      increasingly interest for further studies on the isolation of compounds with
      antiherpetic activity and about the mechanisms of action that produce this
      activity.

PMID- 29334247
TI  - Development of fisetin-loaded folate functionalized pluronic micelles for breast
      cancer targeting.
AB  - The natural flavonoid fisetin (FS) has shown anticancer properties but its in
      vivo administration remains challenging due to its poor aqueous solubility. The
      aim of the study was to develop FS loaded pluronic127 (PF)-folic acid (FA)
      conjugated micelles (FS-PF-FA) by the way of increasing solubility,
      bioavailability and active targetability of FS shall increase its therapeutic
      efficacy. FA-conjugated PF was prepared by carbodiimide crosslinker chemistry. FS
      PF-FA micelles were prepared by thin-film hydration method and evaluated in
      comparison with free FS and FS loaded PF micelles (FS-PF). The smooth surfaces
      with spherical in shape of FS-PF-PF micelles displayed smaller in size (103.2 +/-
      6.1 nm), good encapsulation efficiency (82.50 +/- 1.78%), zeta potential (-26.7
      +/- 0.44 mV) and sustained FS release. Bioavailability of FS from FS-PF-PF
      micelles was increased by 6-fold with long circulation time, slower plasma
      elimination and no sign of tissue toxicity as compared to free FS. Further, the
      FS-PF-FA micelles demonstrated active targeting effect on folate overexpressed
      human breast cancer MCF-7 cells. The concentration of the drug needed for growth
      inhibition of 50% of cells in a designed time period (GI50) was 14.3 +/- 1.2
      ug/ml for FS while it was greatly decreased to 9.8 +/- 0.78 ug/ml, i.e. a 31.46%
      decrease for the FS-PF. Furthermore, the GI50 value for FS-PF-FA was 4.9 +/- 0.4
      ug/ml, i.e. a 65.737% decrease compared to FS and 50% decrease compare to FS-PF.
      The results indicate that the FS-PF-FA micelles have the potential to be applied
      for targeting anticancer drug delivery.

PMID- 29334248
TI  - Nigrosporanenes C and D, two new cyclohexene derivatives from the enphytic fungus
      Nigrospora oryzae S4.
AB  - Two new cyclohexene derivatives, nigrosporanenes C and D (1 and 2), together with
      three known compounds (3-5), were isolated from the culture of an endophyte
      Nigrospora oryzae S4. Their structures were characterized by a combination of
      detailed spectroscopic analysis and comparison of their NMR data with those
      reported in the literature. All compounds were tested for anti-phytopathogenic
      activity, however, none of them showed activity at a concentration of 20 MUM.

PMID- 29334250
TI  - Estimation of a Latent Variable Regression Growth Curve Model for Individuals
      Cross-Classified by Clusters.
AB  - The cross-classified multiple membership latent variable regression (CCMM-LVR)
      model is a recent extension to the three-level latent variable regression (HM3
      LVR) model which can be utilized for longitudinal data that contains individuals
      who changed clusters over time (for instance, student mobility across schools).
      The HM3-LVR model can include the initial status on growth effect as varying
      across those clusters and allows testing of more flexible hypotheses about the
      influence of initial status on growth and of factors that might impact that
      relationship, but only in the presence of pure clustering of participants within
      higher-level units. This Monte Carlo study was conducted to evaluate model
      estimation under a variety of conditions and to measure the impact of ignoring
      cross-classified data when estimating the incorrectly specified HM3-LVR model in
      a scenario in which true values for parameters are known. Furthermore, results
      from a real-data analysis were used to inform the design of the simulation.
      Overall, it would be recommended for researchers to utilize the CCMM-LVR model
      over the HM3-LVR model when individuals are cross-classified, and to use a bare
      minimum of more than 100 clustering units in order to avoid overestimation of the
      level-3 variance component estimates.

PMID- 29334249
TI  - Antimicrobial activity of 1,3,4-oxadiazole derivatives against planktonic cells
      and biofilm of Staphylococcus aureus.
AB  - AIM: Staphylococcus aureus is a major cause of severe hospital-acquired
      infections, and biofilm formation is an important part of staphylococcal
      pathogenesis. Therefore, developing new antimicrobial agents against both
      planktonic cells and biofilm of S. aureus is a major challenge. RESULTS: Three
      1,3,4-oxadiazole derivatives exhibited antimicrobial activity against seven S.
      aureus strains in vitro, with minimum inhibitory concentrations ranging from 4 to
      32 MUg/ml. At 4 * minimum inhibitory concentration, all compounds killed cells
      within 24 h, demonstrating bactericidal activity. In addition to their effects
      against planktonic cells, these compounds prevented biofilm formation in a dose
      dependent manner, with inhibitory concentrations for biofilm formation ranging
      from 8 to 32 MUg/ml. Interestingly, higher concentrations of these compounds were
      effective against mature biofilms and all compounds downregulated the
      transcription of the biofilm-related gene spa. CONCLUSION: We report three new
      1,3,4-oxadiazole derivatives that have bactericidal activity and could provide as
      alternatives to combat S. aureus.

PMID- 29334251
TI  - Discussing edaravone with the ALS patient: an ethical framework from a U.S.
      perspective.
AB  - The recent approval of edaravone by the United States Food and Drug
      Administration has generated a mix of hope tempered by reality. The costs of the
      drug, both monetarily and with regard to intensity of treatment, are high. The
      benefits, while modest, will be viewed through a very different lens by
      individuals depending on their goals of care. By virtue of our training and
      experience, physicians are ideally suited to understand and explain new
      treatments to our patients. As healthcare providers with a fiduciary
      responsibility to our patients, we must make sure they are fully informed about
      both the costs and benefits of non-curative therapies such as edaravone, and be
      prepared to discuss these in the context of their goals of care and potential
      impact on quality of life. Respect for our patients' autonomy is critical when
      discussing these issues, but we should always be guided by the ethical principles
      of beneficence and non-maleficence.

PMID- 29334252
TI  - Impact of paternal nutrition on epigenetic patterns.

PMID- 29334253
TI  - Circular RNA expression in extracellular vesicles isolated from serum of patients
      with endometrial cancer.
AB  - AIM: We aimed to explore the roles of circular RNAs (circRNAs) in extracellular
      vesicles (EVs) isolated from serum of patients with endometrial cancer. MATERIALS
      & METHODS: EVs were isolated from serum samples of three patients with stage III
      adenocarcinoma aged 50-60 years and three matched healthy controls. RNA was
      extracted from the EVs and analyzed using RNA-seq technique. RESULTS: We got 209
      upregulated circRNAs and 66 downregulated circRNAs. Kyoto Encyclopedia of Genes
      and Genomes pathway analysis indicated that the differentially expressed circRNAs
      were enriched in five pathways. The expression level of hsa_circ_0109046 and
      hsa_circ_0002577 was confirmed using real-time quantitative PCR. CONCLUSION: We
      identified 275 differentially expressed circRNAs and the expression level of two
      circRNAs was confirmed using real-time quantitative PCR.

PMID- 29334254
TI  - Antioxidant and anti-proliferative properties of extracts from heterotrophic
      cultures of Galdieria sulphuraria.
AB  - This study explores the possibility to use the extremophilic microalga Galdieria
      sulphuraria (strain 064) as a source of natural biomolecules with beneficial and
      protective effects on human health. Galdieria was cultivated in heterotrophy
      conditions and cells extracts for their antioxidant and anti-proliferative
      properties were tested. Galdieria extracts showed high antioxidant power tested
      through ABTS assay and revealed high glutathione and phycocyanin contents. Based
      on Annexin-V FITC/propidium iodide and MTT analysis, algae extracts inhibited the
      proliferation of human adenocarcinoma A549 cells (51.2% inhibition) through the
      induction of apoptosis without cell cycle arrest. Besides, cytotoxicity and
      cytometry assays showed a positive pro-apoptotic mechanism. On these bases, we
      suggest that G. sulphuraria from heterotrophic culture, for its therapeutic
      potential, could be considered a good candidate for further studies with the aim
      to isolate bioactive anti-cancer molecules.

PMID- 29334255
TI  - NGS-based methylation profiling differentiates TCF3-HLF and TCF3-PBX1 positive B
      cell acute lymphoblastic leukemia.
AB  - AIM: To determine whether methylation differences between mostly fatal TCF3-HLF
      and curable TCF3-PBX1 pediatric acute lymphoblastic leukemia subtypes can be
      associated with differential gene expression and remission. MATERIALS & METHODS:
      Five (extremely rare) TCF3-HLF versus five (very similar) TCF3-PBX1 patients were
      sampled before and after remission and analyzed using reduced representation
      bisulfite sequencing and RNA-sequencing. RESULTS: We identified 7000
      differentially methylated CpG sites between subtypes, of which 78% had lower
      methylation levels in TCF3-HLF. Gene expression was negatively correlated with
      CpG sites in 23 genes. KBTBD11 clearly differed in methylation and expression
      between subtypes and before and after remission in TCF3-HLF samples. CONCLUSION:
      KBTBD11 hypomethylation may be a promising potential target for further
      experimental validation especially for the TCF3-HLF subtype.

PMID- 29334256
TI  - Differential content of secondary metabolites in diploid and tetraploid cytotypes
      of Siegesbeckia orientalis L.
AB  - Siegesbeckia orientalis L. is an annual herb widely distributed throughout the
      world and has many medicinal properties. In Chinese traditional system, it is
      popularly known as Xi-Xian and used for its anti-inflammatory properties. In the
      present study, two cytotypes (diploid and tetraploid) have been investigated for
      their secondary metabolites. The different plant parts have been explored in
      terms of total phenolics, total flavonoids, DPPH radical scavenging acitivity and
      total antioxidant capacity. Out of different plant parts, leaves have the maximum
      amount of secondary metabolites and antioxidant potential. HPTLC technique has
      been applied to quantify six marker compounds in the two cytotypes. Tetraploid
      cytotype has been compared with diploid cytotype, which shows that tetraploid has
      the maximum amount of studied secondary metabolites with high antioxidant
      potential.

PMID- 29334257
TI  - Calaxanthones A-C, three new xanthones from the roots of Calophyllum calaba and
      the cytotoxicity.
AB  - Three new xanthones, named calaxanthones A-C (1-3), along with 17 known xanthones
      (4-20) were isolated from the roots of Calophyllum calaba. Their structures were
      determined by spectroscopic analysis. All isolated compounds were evaluated for
      their cytotoxicity against five cancer cell lines (KB, HeLa S-3, HT-29, MCF-7 and
      HepG-2). Compound 3 showed potent cytotoxicity against all the five cancer cell
      lines with IC50 values in the range of 0.82-5.04 MUM. Furthermore, compound 6
      showed potent cytotoxicity against KB, HeLa S-3 and HepG2 cells with IC50 values
      of 7.06, 5.27 and 9.64 MUM, respectively. Additionally, compound 7 showed potent
      cytotoxicity against KB cell with an IC50 value of 4.62 MUM.

PMID- 29334258
TI  - Two new phenylpropanoid esters from Bulbophyllum retusiusculum.
AB  - Two new phenylpropanoid esters bobulretulates A (1) and B (2), together with
      eleven known compounds, were isolated from the whole plants of Bulbophyllum
      retusiusculum. Their structures were elucidated by means of extensive
      spectroscopic analysis.

PMID- 29334259
TI  - Development of three-dimensional brain arteriovenous malformation model for
      patient communication and young neurosurgeon education.
AB  - PURPOSE: Rapid prototyping technology is used to fabricate three-dimensional (3D)
      brain arteriovenous malformation (AVM) models and facilitate presurgical patient
      communication and medical education for young surgeons. METHODS: Two intracranial
      AVM cases were selected for this study. Using 3D CT angiography or 3D rotational
      angiography images, the brain AVM models were reconstructed on personal computer
      and the rapid prototyping process was completed using a 3D printer. The size and
      morphology of the models were compared to brain digital subtraction arteriography
      of the same patients. 3D brain AVM models were used for preoperative patient
      communication and young neurosurgeon education. RESULTS: Two brain AVM models
      were successfully produced. By neurosurgeons' evaluation, the printed models have
      high fidelity with the actual brain AVM structures of the patients. The patient
      responded positively toward the brain AVM model specific to himself. Twenty
      surgical residents from residency programs tested the brain AVM models and
      provided positive feedback on their usefulness as educational tool and
      resemblance to real brain AVM structures. CONCLUSIONS: Patient-specific 3D
      printed models of brain AVM can be constructed with high fidelity. 3D printed
      brain AVM models are proved to be helpful in preoperative patient consultation,
      surgical planning and resident training.

PMID- 29334260
TI  - Crude extract of Origanum vulgare L. induced cell death and suppressed MAPK and
      PI3/Akt signaling pathways in SW13 and H295R cell lines.
AB  - Oregano (Origanum vulgare L.) is a common aromatic plant used in Mediterranean
      and Asian Regions for treating respiratory diseases, painful menstruation,
      rheumatoid arthritis, etc. Recently its role as an anticancer plant has been
      suggested, although oregano has been never evaluated into adrenocortical tumour
      cell models. This study analysed for the first time the anticancer effects of a
      crude extract of wild mountain oregano (Origanum vulgare L.) in SW13 and H295R
      cell lines. The crude extract was characterised by GC/MS and the toxic effects of
      oregano were first analysed by brine shrimp lethality assay. Our findings
      demonstrated that oregano decreased cell viability, survival, modified cell cycle
      and induced cell death (through necrotic process) and that the effects can be
      attributed to a blockade of MAPK and PI3 K/Akt pathways. These results suggest
      that oregano extract exerts anticancer activities in adrenocortical tumour cell
      lines, providing evidence for further research in higher models.

PMID- 29334261
TI  - Lignans, flavonoids and coumarins from Viola philippica and their alpha
      glucosidase and HCV protease inhibitory activities.
AB  - Two lignans including a new one, five flavonoids and five coumarins were isolated
      from the whole plant of Viola philippica (synonymised as Viola yedoensis Makino).
      The new compound was structurally determined as (7R,8S,8'S) -3,3'-dimethoxy-
      4,4',9-trihydroxy- 7,9'-epoxy-8,8'-lignan 9-O-rutinoside by analysis of its NMR,
      MS and CD spectroscopic data. The known compounds were characterised by comparing
      their NMR and MS data with those reported. Among the known compounds, 5-hydroxy
      4'-methoxyflavone-7-O- rutinoside, 6,7-di-O-beta-D- glucopyranosylesculetin, and
      7R,8S-dihydrodehydrodiconiferyl alcohol 4-O-beta-D- glucopyranoside were isolated
      and identified from this genus for the first time. Of these compounds, 5-hydroxy
      4'-methoxyflavone-7-O-rutinoside and (7R,8S,8'S) -3,3'-dimethoxy- 4,4',9
      trihydroxy- 7,9'-epoxy-8,8'-lignan 9-O-rutinoside were potently active against
      alpha-glucosidase, while the two dimeric coumarins, 5, 5'-bi (6, 7
      dihydroxycoumarin) and 6,6',7,7'-tetrahydroxy-5,8'-bicoumarin potently inhibited
      HCV protease.

PMID- 29334262
TI  - A multicentre study on unattended automated office blood pressure measurement in
      treated hypertensive patients.
AB  - AIMS: Unattended automated office blood pressure (uAutoOBP) may eliminate white
      coat effect. In the present study, we studied its relationships to attended
      office blood pressure (BP) and ambulatory BP monitoring (ABPM). MATERIAL AND
      METHODS: Stable treated hypertensive subjects were examined in four Czech
      academic hypertension centres. uAutoOBP was measured with the BP Tru device;
      attended BP was measured six times: three times with auscultatory method
      (AuscOBP) by the physician followed optionally by three oscillometric
      measurements (OscOBP). ABPM was performed within one week from the clinical
      visit. RESULTS: Data on 172 subjects aged 63.7 +/- 12.4 years with AuscOBP 127.6
      +/- 12.1/77.6 +/- 10.0 mm Hg are reported. uAutoOBP was by 8.5 +/- 9.0/3.0 +/-
      6.1 mm Hg lower than AuscOBP. The AuscOBP-uAutoOBP difference increased with the
      AuscOBP level and it did not depend on any other factor. OscOBP differed by 8.6
      +/- 8.6/1.9 +/- 5.7 mm Hg from uAutoOBP. 24-hour mean BP was by 4.2 +/- 12.1/3.5
      +/- 7.8 mm Hg lower than AuscOBP and by 4.3 +/- 11.0/0.5 +/- 6.9 mm Hg higher
      than uAutoOBP; the correlation coefficients of 24-hour mean BP with AuscOBP and
      with uAutoOBP did not differ (p for difference >=.13). In the lowest BP group
      (systolic AuscOBP <120 mm Hg or diastolic AuscOBP <70 mm Hg), both AuscOBP and
      uAutoOBP were lower than 24-hour mean BP, while in the highest BP group (systolic
      AuscOBP >=140 mm Hg or diastolic AuscOBP >=90 mm Hg), they were higher.
      CONCLUSIONS: Compared to uAutoOBP, attended BP measurement gives higher values,
      both when measured with auscultatory or oscillometric method. Inter-individual
      variability of AutoOBP - uAuscOBP difference, as well of uAutoOBP - ABPM
      difference, is large. We did not prove that uAutoOBP would be associated to 24
      hour ambulatory BP more closely than attended BP.

PMID- 29334263
TI  - New cytotoxic natural products from the mangrove biome: covering the period 2007
      2015.
AB  - Nowadays, the mangrove biome is considered to be a profound resource of natural
      products usually possessing cytotoxicity of a broader range. Covering the period
      2007-2015, a total of 21 new naturally occurring compounds has stood out. For
      example, xylogranin B and swietephragmin C were found to exhibit very potent
      cytotoxic activity against the colon HCT-116 cells reaching IC50 values of 0.05
      and 0.06 MUM, respectively. Bearing in mind the efficacy of the majority
      compounds in the preliminary in vitro screens, these studies should be expanded
      to both ex vivo and in vivo screens including the evaluation of the relevant
      toxicological profiles.

PMID- 29334264
TI  - Antifungal activity of phenolic monoterpenes and structure-related compounds
      against plant pathogenic fungi.
AB  - The aim of this work is to explore the possibility of using the phenolic
      monoterpenes (PMs) as leading compounds with antifungal activity against plant
      disease. The in vitro antifungal activities of carvacrol and thymol against seven
      kinds of plant pathogenic fungi were evaluated on mycelium growth rate method,
      and the results showed that carvacrol and thymol exhibited broad spectrum
      antifungal activity. Structure requirement for the antifungal activity of PMs was
      also investigated. The preliminary conclusion was that phenolic hydroxyl and
      monoterpene were basic structures for the antifungal activity of PMs, and the
      position of phenolic hydroxyl showed less effect. Ester derivatives of carvacrol
      and thymol were more effective than carvacrol and thymol against plant pathogenic
      fungi. We suggested that carvacrol, thymol and their ester derivatives could
      potentially be used as new fungicide leading compounds.

PMID- 29334265
TI  - Prevalence and covariates of uncontrolled hypertension in ischemic stroke
      survivors: the Norwegian stroke in the young study.
AB  - PURPOSE: Hypertension is the most important modifiable risk factor for stroke.
      Few data are available on control of hypertension in younger ischemic stroke
      survivors. MATERIAL AND METHODS: We assessed clinic and ambulatory blood pressure
      (BP) measurements in 320 patients aged 15-60 years (mean 48 +/- 10) included in
      the Norwegian Stroke in the Young Study during 3-months follow-up after the index
      stroke. Controlled hypertension was defined as ambulatory BP <130/80 mmHg.
      Carotid-femoral pulse wave velocity (PWV) was measured by applanation tonometry.
      Carotid plaque was considered present if focal intima-media thickness >1.5 mm.
      RESULTS: At hospital discharge, 58% of the patients were treated for
      hypertension. Another 9% of the total study population was diagnosed with new
      onset hypertension during follow-up. At the 3-months follow-up visit, 56% of
      patients with treated hypertension were uncontrolled. Patients with uncontrolled
      treated hypertension were older, had higher body mass index (BMI) and PWV, and
      were more likely to have diabetes and carotid plaques compared to patients with
      normotension (p < .01). Compared to controlled treated hypertension, patients
      with uncontrolled treated hypertension had higher prevalence of carotid plaque (p
      < .01). In a multivariate logistic regression, uncontrolled treated hypertension
      was associated with higher PWV and BMI, and presence of carotid plaque,
      independent of the more intensified use of antihypertensive treatment (all p <
      .05). CONCLUSION: Uncontrolled hypertension was highly prevalent in ischemic
      stroke survivors <60 years and associated with co-presence of obesity and
      functional and structural arterial damage. Our results highlight the unmet
      potential and challenge of optimization of hypertension diagnosis and management
      in order to prevent recurrent vascular events in ischemic stroke survivors.

PMID- 29334266
TI  - Hyaluronic acid modified daunorubicin plus honokiol cationic liposomes for the
      treatment of breast cancer along with the elimination vasculogenic mimicry
      channels.
AB  - BACKGROUND: Breast cancer is an alarming global public health problem and a main
      cause of cancer-related death in women. Systemic chemotherapy is the most widely
      used treatment for breast cancer. However, current chemotherapy treatments are
      far from desirable due to poor targeting specificity, severe side effects and
      vasculogenic mimicry (VM). PURPOSE: Hyaluronic acid (HA)-modified daunorubicin
      plus honokiol (HNK) cationic liposomes were prepared and characterised for
      treatment of breast cancer by eliminating VM. METHODS: HA-modified daunorubicin
      plus HNK cationic liposomes were prepared by a thin-film hydration method.
      Evaluations were performed on MCF-7 cells and MDA-MB-435S cells, which are human
      breast cancer cells, and xenografts of MDA-MB-435S cells. RESULTS: In vitro
      results revealed that the HA-modified daunorubicin plus HNK cationic liposomes
      enhanced the cellular uptake and destroyed VM channels. In vivo results
      demonstrated that the liposomes prolonged the circulation time in the blood,
      obviously accumulated in the tumour region, and enhanced the overall anticancer
      effects. Action mechanisms were related to down-regulation of VM protein
      indicators including FAK, EphA2, MMP-2 and MMP-9. CONCLUSIONS: The prepared HA
      modified daunorubicin plus HNK cationic liposomes may serve as a promising
      therapeutic strategy for the treatment of breast cancer.

PMID- 29334268
TI  - Analysis of the development and progression of carbon monoxide poisoning-related
      acute kidney injury according to the Kidney Disease Improving Global Outcomes
      (KDIGO) criteria.
AB  - CONTEXT: Acute kidney injury (AKI) can occur after carbon monoxide (CO)
      intoxication; however, limited data are available. This study aimed to evaluate
      the prognostic value of the development and progression of AKI in patients with
      acute CO poisoning. MATERIALS AND METHODS: We conducted a retrospective cohort
      study using a prospective registry of CO poisoning between January 2010 and
      December 2015. AKI was defined and classified according to the Kidney Disease
      Improving Global Outcomes (KDIGO) criteria. Multivariate logistic regression
      analysis was conducted to determine the association between AKI and adverse
      outcomes, defined as neurological deficits at discharge or 28-day mortality.
      RESULTS: A total of 661 patients were evaluated. According to KDIGO criteria, 114
      patients (17.2%) had AKI (initial: stage 1, 70.2%; stage 2, 26.3%; stage 3, 3.5%)
      on admission and 119 (18.0%) finally developed AKI during their hospital stay
      (maximum: stage 1, 68.9%; stage 2, 23.5%; stage 3, 7.6%). Almost all patients
      (99.2%) were diagnosed as having their highest KDIGO stage within three days
      (median, one day). AKI development was associated with adverse outcomes (odds
      ratio (OR) 17.53, 95% confidence interval 45.00-77.14). Both initial and maximum
      AKI stages demonstrated a stepwise increase of adjusted OR for adverse outcomes.
      AKI stage progression occurred in 8.4% of patients with AKI and was an
      independent factor for adverse outcomes. CONCLUSION: CO poisoning- related AKI
      occurred in 18% and was mostly detected within one day after CO intoxication. The
      development and progression of AKI had a strong association with adverse outcomes
      and deserve further prospective investigation.

PMID- 29334269
TI  - Effects of a transient noise reduction algorithm on speech intelligibility in
      noise, noise tolerance and perceived annoyance in cochlear implant users.
AB  - OBJECTIVE: To evaluate the validity and efficacy of a transient noise reduction
      algorithm (TNR) in cochlear implant processing and the interaction of TNR with a
      continuous noise reduction algorithm (CNR). DESIGN: We studied the effects of TNR
      and CNR on the perception of realistic sound samples with transients, using
      subjective ratings of annoyance, a speech-in-noise test and a noise tolerance
      test. STUDY SAMPLE: Participants were 16 experienced cochlear implant recipients
      wearing an Advanced Bionics Naida Q70 processor. RESULTS: CI users rated sounds
      with transients as moderately annoying. Annoyance was slightly, but significantly
      reduced by TNR. Transients caused a large decrease in speech intelligibility in
      noise and a moderate decrease in noise tolerance, measured on the Acceptable
      Noise Level test. The TNR had no significant effect on noise tolerance or on
      speech intelligibility in noise. The combined application of TNR and CNR did not
      result in interactions. CONCLUSIONS: The TNR algorithm was effective in reducing
      annoyance from transient sounds, but was not able to prevent a decreasing effect
      of transients on speech understanding in noise and noise tolerance. TNR did not
      reduce the beneficial effect of CNR on speech intelligibility in noise, but no
      cumulated improvement was found either.

PMID- 29334270
TI  - Secukinumab in multi-failure psoriatic patients: the last hope?
AB  - Psoriasis is a multi-systemic chronic inflammatory disease that affects about 1.5
      3% of the general population, of which almost 20% suffer from a moderate-severe
      form. Those patients can be treated with a systemic agent and in case of scarce
      response or contraindications, they may require a biologic therapy, such as tumor
      necrosis factor or interleukin-12/23 inhibitors. When also these agents fail,
      clinicians face a true therapeutic challenge. We report a case series of multi
      failure 16 patients, successfully treated with secukinumab, a human monoclonal
      antibody that selectively neutralizes interleukin-17 A and is recently approved
      for the treatment of plaque psoriasis, psoriatic arthritis, and ankylosing
      spondylitis.

PMID- 29334271
TI  - The safety of available treatments of male hypogonadism in organic and functional
      hypogonadism.
AB  - INTRODUCTION: In the case of primary male hypogonadism (HG), only testosterone
      (T) replacement therapy (TRT) is possible whereas when the problem is secondary
      to a pituitary or hypothalamus alteration both T production and fertility can be,
      theoretically, restored. We here systematically reviewed and discussed the
      advantages and limits of medications formally approved for the treatment of HG.
      Areas covered: Data derived from available meta-analyses of placebo controlled
      randomized trials (RCTs) were considered and analyzed. Gonadotropins are well
      toleratedand their use is mainly limited by higher costs and a more cumbersome
      treatment schedule than TRT. Available RCTs on TRT suggest that cardiovascular
      (CV) and venous thromboembolism risk is not a major issue and that prostate
      safety is guaranteed. The risk of increased hematocrit is mainly limited to the
      use of short terminjectable preparations. Expert opinion: In the last few years
      the concept of 'organic' irreversible HG and 'functional' or age- and comorbidity
      related HG has been introduced. This definition is not evidence-based. The
      majority of RCTs enrolled patients with 'functional' HG. Considering the
      significant improvement in body composition, glucose metabolism and sexual
      activity, TRT should not be limited to 'organic' HG, but also offered for
      'functional'.

PMID- 29334273
TI  - The Barthel Index and the Cumulated Ambulation Score are superior to the de
      Morton Mobility Index for the early assessment of outcome in patients with a hip
      fracture admitted to an acute geriatric ward.
AB  - PURPOSE: To examine clinimetric properties of the de Morton Mobility Index
      (DEMMI) in patients with hip fracture in comparison with the modified Barthel
      Index (BI), Cumulated Ambulation Score (CAS), and 30-s Chair Stand Test (30-s
      CST). MATERIALS AND METHODS: Two hundred and twenty two patients with a hip
      fracture admitted to a geriatric ward following surgery were assessed on day 1
      and at discharge (mean of 9 [SD 5.1] post-surgery days). RESULTS: Ninety eight
      percent and 89% of patients were not able to perform the 30-s CST at baseline and
      at discharge (large floor effect), respectively. Corresponding floor effects were
      39% and 31% for DEMMI, 12% and 5% for BI, and 22% and 6%, respectively, for CAS.
      Convergent validity was strong between DEMMI and CAS (r = 0.76, 95% CI: 0.69
      0.81), and moderate between DEMMI and BI (r = 0.58, 95% CI: 0.48-0.66) and CAS
      and BI (r = 0.49, 95% CI: 0.39-0.59). Responsiveness, as indicated by the effect
      size was 0.76 for DEMMI, 1.78 for BI and 1.04 for CAS. Baseline scores of DEMMI,
      BI, and CAS showed similar properties in predicting discharge destination of
      patients from own home. CONCLUSIONS: The value of using DEMMI and 30-s CST in
      patients with hip fracture during the acute hospitalization seems limited in
      comparison with BI and CAS. DEMMI and CAS seem to assess similar constructs.
      Implications for Rehabilitation Outcome measures used for the evaluation of
      patients with hip fracture should be validated in the specific time-line and
      rehabilitation setting following surgery, before being implemented in daily
      clinical practice. We suggest the Cumulated Ambulation Score for monitoring basic
      mobility during the acute hospitalization for the entire group of patients
      recovering from a hip fracture, while DEMMI seems more feasible for the subgroup
      of patients with higher functional levels. The modified Barthel Index seems
      useful for the assessment of activities of daily living in the acute care setting
      of patients with hip fracture. We cannot recommend the original 30-s Chair Stand
      Test to be used for the evaluation of patients with hip fracture in the acute
      hospital setting.

PMID- 29334272
TI  - Extracellular vesicle-mimetic nanovesicles transport LncRNA-H19 as competing
      endogenous RNA for the treatment of diabetic wounds.
AB  - Diabetic wounds, one of the most enervating complications of diabetes mellitus,
      affect millions of people worldwide annually. Vascular insufficiency, caused by
      hyperglycemia, is one of the primary causes and categories of diabetic impaired
      wound healing. Recently, long noncoding RNA (LncRNA)-H19, which is significantly
      decreased in diabetes and may be crucial in triggering angiogenesis, has
      attracted increasing interest. The possible relationship between the decrease of
      LncRNA-H19 and the impairment of angiogenesis in diabetes could involve
      impairment of the insulin-phosphatidylinositol 3-kinase (PI3K)-Akt pathway via
      the interdiction of LncRNA-H19. Thus, a therapeutic strategy utilizing LncRNA-H19
      delivery is feasible. In this study, we investigated the possibility of using
      high-yield extracellular vesicle-mimetic nanovesicles (EMNVs) as an effective
      nano-drug delivery system for LncRNA, and studied the function of EMNVs with a
      high content of LncRNA-H19 (H19EMNVs). The results, which were exciting, showed
      that H19EMNVs had a strong ability to neutralize the regeneration-inhibiting
      effect of hyperglycemia, and could remarkably accelerate the healing processes of
      chronic wounds. Our results suggest that bioengineered EMNVs can serve as a
      powerful instrument to effectively deliver LncRNA and will be an extremely
      promising multifunctional drug delivery system in the immediate future.

PMID- 29334274
TI  - An overview of robotic/mechanical devices for post-stroke thumb rehabilitation.
AB  - PURPOSE: This article aims to clarify the current state-of-the-art of
      robotic/mechanical devices for post-stroke thumb rehabilitation as well as the
      anatomical characteristics and motions of the thumb that are crucial for the
      development of any device that aims to support its motion. METHODS: A systematic
      literature search was conducted to identify robotic/mechanical devices for post
      stroke thumb rehabilitation. Specific electronic databases and well-defined
      search terms and inclusion/exclusion criteria were used for such purpose. A
      reasoning model was devised to support the structured abstraction of relevant
      data from the literature of interest. RESULTS: Following the main search and
      after removing duplicated and other non-relevant studies, 68 articles
      (corresponding to 32 devices) were left for further examination. These articles
      were analyzed to extract data relative to (i) the motions assisted/permitted -
      either actively or passively - by the device per anatomical joint of the thumb
      and (ii) mechanical-related aspects (i.e., architecture, connections to thumb,
      other fingers supported, adjustability to different hand sizes, actuators - type,
      quantity, location, power transmission and motion trajectory). CONCLUSIONS: Most
      articles describe preliminary design and testing of prototypes, rather than the
      thorough evaluation of commercially ready devices. Defining appropriate kinematic
      models of the thumb upon which to design such devices still remains a challenging
      and unresolved task. Further research is needed before these devices can actually
      be implemented in clinical environments to serve their intended purpose of
      complementing the labour of therapists by facilitating intensive treatment with
      precise and repeatable exercises. Implications for Rehabilitation Post-stroke
      functional disability of the hand, and particularly of the thumb, significantly
      affects the capability to perform activities of daily living, threatening the
      independence and quality of life of the stroke survivors. The latest studies show
      that a high-dose intensive therapy (in terms of frequency, duration and
      intensity/effort) is the key to effectively modify neural organization and
      recover the motor skills that were lost after a stroke. Conventional therapy
      based on manual interaction with physical therapists makes the procedure labour
      intensive and increases the costs. Robotic/mechanical devices hold promise for
      complementing conventional post-stroke therapy. Specifically, these devices can
      provide reliable and accurate therapy for long periods of time without the
      associated fatigue. Also, they can be used as a means to assess patients?
      performance and progress in an objective and consistent manner. The full
      potential of robot-assisted therapy is still to be unveiled. Further exploration
      will surely lead to devices that can be well accepted equally by therapists and
      patients and that can be useful both in clinical and home-based rehabilitation
      practice such that motor recovery of the hand becomes a common outcome in stroke
      survivors. This overview provides the reader, possibly a designer of such a
      device, with a complete overview of the state-of-the-art of robotic/mechanical
      devices consisting of or including features for the rehabilitation of the thumb.
      Also, we clarify the anatomical characteristics and motions of the thumb that are
      crucial for the development of any device that aims to support its motion.
      Hopefully, this?combined with the outlined opportunities for further
      research?leads to the improvement of current devices and the development of new
      technology and knowledge in the field.

PMID- 29334275
TI  - Laparoscopic ovarian drilling versus GnRH antagonist combined with cabergoline as
      a prophylaxis against the re-development of ovarian hyperstimulation syndrome.
AB  - OBJECTIVE: The aim of this work was to investigate the value of laparoscopic
      ovarian drilling (LOD) compared with GnRH antagonist flexible protocol combined
      with cabergoline (Cb), as a prophylaxis against the re-development of ovarian
      hyperstimulation syndrome (OHSS) in women with clomiphene citrate-resistant
      polycystic ovary disease (CCR-PCOD) who had severe OHSS before in a previous ICSI
      cycle. STUDY DESIGN: It is a prospective controlled study, where 250 CCR-PCOD
      women (n = 250) with a history of severe OHSS before, had been recruited for the
      study. LOD had been performed for 120 (n = 120) of the recruited women before
      ovarian induction, and considered as group A. GnRH antagonist (Cetrotide 0.25 mg)
      was added when a leading follicle reaches 14-16 mm combined with oral Cb in a
      dose 0.5 mg a day before hCG, and for 8 d for another 130 (n = 130) women, and
      considered as group B. Pregnancy was diagnosed with BhCG level >=25 IU/L, +/- 14
      d after embryo transfer, followed with transvaginal ultrasound scanning (TVS) 2
      weeks later to confirm intra-uterine pregnancy (IUP). Women were followed up
      weekly for 3 months for the possible development of any signs and symptoms of
      OHSS. RESULTS: None of the participants in group A developed severe OHSS, and
      only six women (5%) developed mild to moderate OHSS. The incidence of severe OHSS
      was significantly higher (n = 3, 15%) in group B compared with group A (p <
      .001). Another (n = 17, 13.3%) women in group B developed mild to moderate OHSS.
      The probability of developing severe OHSS was also significantly higher in group
      B as well (p = .031). Pregnancy rate (PR) was significantly higher in group A
      more than group B (67% versus 39%, respectively), and all were single
      intrauterine pregnancies (IUP) and all developed after fresh embryo transfer
      (ET), compared with frozen embryo transfer (FET) which was performed in 42 cases
      in group B after postponing ET due to significantly severe OHSS developed.
      CONCLUSION: LOD could be considered a good prophylactic measure against OHSS, in
      addition to improving the total outcome of IVF cycles in women with CCR-PCOS.

PMID- 29334277
TI  - Validation of DPOAE screening conducted by village health workers in a rural
      community with real-time click evoked tele-auditory brainstem response.
AB  - OBJECTIVE: This study assessed the validity of DPOAE screening conducted by
      village health workers (VHWs) in a rural community. Real-time click evoked tele
      auditory brainstem response (tele-ABR) was used as the gold standard to establish
      validity. DESIGN: A cross-sectional design was utilised to compare the results of
      screening by VHWs to those obtained via tele-ABR. Study samples: One hundred and
      nineteen subjects (0 to 5 years) were selected randomly from a sample of 2880
      infants and young children who received DPOAE screening by VHWs. METHOD: Real
      time tele-ABR was conducted by using satellite or broadband internet connectivity
      at the village. An audiologist located at the tertiary care hospital conducted
      tele-ABR testing through a remote computing paradigm. Tele-ABR was recorded using
      standard recording parameters recommended for infants and young children. Wave
      morphology, repeatability and peak latency data were used for ABR analysis.
      RESULTS: Tele-ABR and DPOAE findings were compared for 197 ears. The sensitivity
      of DPOAE screening conducted by the VHW was 75%, and specificity was 91%. The
      negative and positive predictive values were 98.8% and 27.2%, respectively.
      CONCLUSIONS: The validity of DPOAE screening conducted by trained VHW was
      acceptable. This study supports the engagement of grass-root workers in community
      based hearing health care provision.

PMID- 29334276
TI  - An automatic measure of progression during colonoscopy correlates to patient
      experienced pain.
AB  - BACKGROUND: Colonoscopy screening and surveillance programs depend on patient's
      tolerable experience, which is associated with competence of the endoscopist. The
      Colonoscopy Progression Score (CoPS) is an automated tool based on recording of
      the Magnetic Scope Imager (MEI) picture in order to track progression. CoPS
      deliver a numeric score and a graphic map. A high score expresses a rapid and
      smooth progression. Aims of study were to explore the correlation between CoPS
      and patient experienced pain and to identity locations associated with pain.
      METHODS AND MATERIALS: Patients listed for colonoscopy were included and asked to
      reply to pain by pressing a rubber ball. The signal was recorded simultaneous to
      CoPS. Patients evaluated the experience on a Visual Analogue Scale (VAS). CoPS
      and recorded pain events were used to create a pain sensitive CoPS-map (S-CoPS
      map). RESULTS: A total of 58 complete recordings were used for evaluation. We
      demonstrated a moderate correlation between CoPS and patient experienced pain,
      Pearson's r = -0.47 (p < .001). A low CoPS was associated with a painful
      colonoscopy and a high CoPS excluded severe pain. Sensitivity and specificity was
      0.79 and 0.60 and AUC was 0.61 Passage of the sigmoid colon, right and left
      flexures were associated with pain for 51%, 33% and 25% of the patients,
      respectively. CONCLUSION: A moderate correlation between CoPS and patient
      experienced pain suggest that CoPS measure inserting skills but might also be a
      measure of a gentle performance. The graphic S-CoPS-map can be used to point-out
      painful passages and aid planning of future colonoscopies.

PMID- 29334278
TI  - A comparative safety review between GLP-1 receptor agonists and SGLT2 inhibitors
      for diabetes treatment.
AB  - INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium
      glucose cotransporter 2 inhibitors (SGLT2i) are of particular interest in type 2
      diabetes treatment strategies, due to their efficacy in reducing HbA1c with a low
      risk of hypoglycaemia, to their positive effects on body weight and blood
      pressure and in light of their effects on cardiovascular risk and on
      nephroprotection emerged from the most recent cardiovascular outcome trials.
      Since it is therefore very likely that GLP-1RA and SGLT2i use will become more
      and more common, it is more and more important to gather and discuss information
      about their safety profile. Area Covered: adverse events and the safety concerns
      most often emerged in trials with GLP-1RA namely, exenatide long acting release
      (LAR), dulaglutide, liraglutide, semaglutide, lixisenatide or SGLT2i, namely
      empagliflozin, dapagliflozin, canagliflozin and SGLT2i with an attempt at
      comparing the safety profiles of molecules of these two classes. Expert opinion:
      GLP-1RA and SGLT2i, although each associated with different specific side
      effects, share a 'similar' safety profile and are both drugs relatively easy to
      handle. The potentially complementary mechanisms of action, the cardio and
      nephroprotective effects demonstrated by molecules of both classes, make these
      drugs potentially useful even in add on to each other.

PMID- 29334279
TI  - Uric acid and the vaccine adjuvant activity of aluminium (oxy)hydroxide
      nanoparticles.
AB  - In an effort to improve the adjuvanticity of insoluble aluminium salts, we
      discovered that the adjuvant activity of aluminium salt nanoparticles is
      significantly stronger than aluminium salt microparticles, likely related to
      nanoparticle's stronger ability to directly activate NACHT, LRR and PYD domains
      containing protein 3 (NLRP3) inflammasome as the nanoparticles are more
      efficiently taken up by phagocytic cells. Endogenous signals such as uric acid
      from cell damage or death caused by the cytotoxicity of aluminium salts are
      thought to indirectly activate inflammasome, prompting us to hypothesise that the
      potent adjuvant activity of aluminium salt nanoparticles is also related to their
      ability to stimulate uric acid production. In the present study, we prepared
      aluminium (oxy)hydroxide nanoparticles (~ 30-100 nm) and microparticles (X50,
      9.43 MUm) and showed that intraperitoneal injection of mice with the
      nanoparticles, absorbed with ovalbumin, led to a significant increase in uric
      acid level in the peritoneal lavage, whereas the microparticles did not. The
      aluminium (oxy)hydroxide nanoparticles' ability to stimulate uric acid production
      was also confirmed in cell culture. We concluded that the stronger adjuvant
      activity of insoluble aluminium (oxy)hydroxide nanoparticles, relative to
      microparticles, may be attributed at least in part to their stronger ability to
      induce endogenous danger signals such as uric acid.

PMID- 29334280
TI  - Comparison of guidelines for the use of TNF inhibitors for psoriasis in the
      United States, Canada, Europe and the United Kingdom: a critical appraisal and
      comprehensive review.
AB  - PURPOSE: To compare and contrast evidence-based CPGs from leading dermatological
      organizations for the use of tumor necrosis factor inhibitors (TNFi) in
      psoriasis. MATERIALS AND METHODS: Guidelines from the British National Institute
      for Health and Care Excellence (NICE), the British Association of Dermatologists
      (BAD), the American Academy of Dermatology (AAD), the National Psoriasis
      Foundation (NPF), and the Canadian Dermatology Association (CDA) were reviewed
      and compared. RESULTS: Various guidelines are similar regarding treatment
      initiation but have significant differences regarding topics such as continuous
      versus intermittent therapy, use in erythrodermic and pustular palmoplantar
      psoriasis and special patient populations. CONCLUSION: TNF inhibitors remain
      valuable tools in psoriasis therapy, and guidelines for their use may help
      clinicians use them effectively.

PMID- 29334281
TI  - Learning with unwell patients in the intensive care unit.

PMID- 29334282
TI  - Evaluation of dentin permeability of fluorotic permanent teeth.
AB  - OBJECTIVE: The in vitro permeability characteristics of dentin have been studied
      extensively and used to evaluate the efficacy of various preventative and
      restorative procedures. The aim of this in vitro study was to precisely determine
      the dentin permeability of fluorotic premolar teeth using an electronic hydraulic
      conductance measurement system with photosensors and to compare the data with
      healthy premolars. METHODS: In total, 40 fluorotic and healthy premolar teeth
      with complete root formation that were extracted for orthodontic purposes and had
      no caries, restoration, fractures, or cracks were selected for this study. Teeth
      were classified according to a modified form of the dental fluorosis index of
      Thylstrup and Fejerskov. The dentin discs were placed in an electronic hydraulic
      conductance measurement system equipped with photosensors, which was designed for
      measurements of dentin permeability. The amount of distilled water passed through
      each dentin disc (MUL/min) under a constant pressure was determined. Dentin
      permeability data of the fluorotic and healthy teeth were recorded and analyzed
      statistically. RESULTS: The present study showed that fluorosis influenced the
      volume of fluid that passed through the dentin and the dentin permeability was
      decreased, whereas dental fluorosis severity was increased in permanent teeth.
      CONCLUSION: The number of teeth with fluorosis is increasing, depending on
      fluorine sources, so more appropriate treatments will need to be evaluated by
      standardizing the methods employed in related studies.

PMID- 29334283
TI  - Effects of an exercise program on the physiological, biological and psychological
      profiles in patients with mood disorders: a pilot study.
AB  - OBJECTIVE: The objective of this study is to assess the impact of an 8-week
      physical training program on physiological, biological and psychological profiles
      in individual with mood disorders. METHODS: Seven patients participated in the
      study. Patients were trained twice weekly (75 min/session) for 8 weeks. The
      training program aimed to improve muscular and cardiorespiratory reserves as well
      as functional capacity. Bioassays were also measured (lipid profile, blood
      glucose and cortisol). Depression, sleep quality and body image dissatisfaction
      were assessed. All measures were administrated at pre/post-intervention. RESULTS:
      At post-intervention, 13 of the 15 physiological fitness, muscular strength and
      functional capacity variables improved significantly (p < .05). In addition,
      change in cortisol levels represented a medium to large effect size (Cohen's d = 
      0.67) which indicates a clinical reduction of stress-related symptoms. Depression
      was significantly improved (Cohen's d = -0.47; p = .027). Sleep and body image
      showed a trend-level improvement. CONCLUSIONS: An 8-week periodised training
      program improved physiological, biological and psychological profiles in patients
      with mood disorders.

PMID- 29334284
TI  - Surface endoglin (CD105) expression on acute leukemia blast cells: an extensive
      flow cytometry study of 1002 patients.

PMID- 29334285
TI  - What should we mean by "allowed to supervise others" in entrustment scales?

PMID- 29334286
TI  - An editorial on the article 'Patents in the Diabetes Area in the Years 2008
      2016'.

PMID- 29334287
TI  - Efficacy and safety of alpha blockers in medical expulsive therapy for ureteral
      stones: a mixed treatment network meta-analysis and trial sequential analysis of
      randomized controlled clinical trials.
AB  - INTRODUCTION: Alpha blockers (AB) are the main group of drugs used for medical
      expulsive therapy (MET) in patients with ureteral stones. However, there is no
      consensus on the relative efficacy and safety of individual AB in MET. Areas
      covered: The present work is a network meta-analysis of randomized controlled
      trials comparing AB with either placebo or standard of care in patients with
      ureteral stones. Electronic databases of Medline, Cochrane CENTRAL and Google
      Scholar were searched for eligible clinical studies. Inverse variance
      heterogeneity model was used for mixed treatment comparisons. Stone expulsion
      rate (SER) and stone expulsion time (SET) were the primary outcomes. Sub-group
      analyses for the following sub-groups were carried out: children; after shockwave
      lithotripsy; stone size of <=5 mm; >5 mm; proximal and distal ureteral stones.
      Expert review: AB, phosphodiesterase inhibitors and combined AB with
      corticosteroids were observed with significant stone expulsion rate compared to
      control group in a recent network meta-analysis. Due to lack of head-to-head
      clinical trials within AB, only tamsulosin has been widely recommended by various
      urological guidelines. The results of this network meta-analysis will guide the
      future researchers in evaluating other promising ABs as agents for MET.

PMID- 29334288
TI  - Targeted anti-IL-13 therapies in asthma: current data and future perspectives.
AB  - INTRODUCTION: The identification of patients with severe asthma who will benefit
      from a personalized management approach remains an unmet need. Interleukin-13 (IL
      13) is a cytokine possessing a significant role in asthma pathogenesis and
      progression of disease. Humanised monoclonal antibodies against IL-13 and IL-13
      and IL-4 receptors are mainly proposed as add-on therapy in patients with TH2
      high inflammation with uncontrolled asthma despite maximum therapy. Areas
      covered: The role of IL-13 in airway inflammation in severe asthma, the targeted
      anti-IL-13 therapies and biomarkers that predict response to anti-IL-13 treatment
      are discussed. Expert opinion: New effective individualized therapies in severe
      asthma are urgently needed to block specific inflammatory pathways using
      monoclonal antibodies. Studies on anti-IL-13 therapies showed that asthmatic
      patients could benefit from this novel targeted therapy as far as lung function
      and exacerbation rate are concerned. TH2-high and especially periostin-high
      groups of asthmatics with moderate-to-severe uncontrolled asthma seem to compose
      the group that could benefit from anti-IL-13 therapy. Targeting IL-13 alone may
      not be sufficient to achieve asthma control. Inhibition of IL-13 and IL-4 with
      mabs may be more encouraging and patients will probably have additional benefits
      from these therapeutic interventions because of IL-13/IL-4 overlapping actions in
      asthma pathophysiology.

PMID- 29334289
TI  - The extracellular matrix-degrading protein ADAMTS5 is expressed in the nuclei of
      urothelial cells in healthy rats.
AB  - OBJECTIVE: The aim of this study was to investigate whether protein expression of
      the extracellular matrix-degrading protease ADAMTS5 can be demonstrated in the
      urinary bladder of healthy rats, and, if so, to determine the localization of
      this enzyme. MATERIALS AND METHODS: The experiments were conducted with eight
      inbred male Sprague-Dawley rats. Immunohistochemistry was used to investigate the
      expression of ADAMTS5 in the urinary bladder. Negative controls were established
      by either excluding the primary antibody or applying the antibody after it had
      been preabsorbed with its immunogenic peptide. Confocal microscopy was used to
      visualize the distribution of ADAMTS5 in the urinary bladder tissue. RESULTS:
      Immunoreactivity for ADAMTS5 was demonstrated in the urothelium and in the
      detrusor. This expression was localized not only in the cytoplasm, but also in
      the nuclei. Confocal microscopy corroborated these findings. CONCLUSION:
      Expression of ADAMTS5 was demonstrated in the cytoplasm as well as in the nuclei
      of the urothelium and detrusor cells, suggesting that it may play a role at the
      transcriptional level.

PMID- 29334290
TI  - Topical lidocaine-prilocaine cream versus lidocaine infiltration for pain relief
      during repair of perineal tears after vaginal delivery: randomized clinical
      trial.
AB  - OBJECTIVE: The current study aims to compare the analgesic effect of lidocaine
      prilocaine (LP) cream with lidocaine infiltration during repair of perineal tears
      after vaginal delivery. MATERIALS AND METHODS: A single center open-labeled
      randomized clinical trial was carried out in a tertiary University Hospital
      between October 2016 and May 2017 (Clinical Trials.Gov: NCT02883179). We included
      parous women, who delivered at gestational age >37 weeks with first- or second
      degree perineal tears. The participants were randomized in a 1:1 ratio to either
      lidocaine infiltration (Group I); or application of LP cream (Group II) for pain
      relief during perineal repair. The primary outcome was the difference in mean
      pain score during perineal repair. Secondary outcomes included the participants'
      satisfaction, the need for additional anesthesia, the duration of perineal
      repair, and the rate of adverse effects of both medications. RESULTS: The study
      included 144 participants randomized to both groups. The mean pain score during
      perineal repair was significantly lower in the LP cream group (3.86 +/- 1.59)
      than the lidocaine infiltration group (5.99 +/- 1.47) [p = .001]. The duration of
      repair was significantly shorter in the LP group than the lidocaine infiltration
      group (6.37 +/- 3.68 versus 8.17 +/- 2.75 min, respectively, p = .001). The need
      for additional anesthesia was quite similar in both groups (p = .371). More women
      in the LP cream group were satisfied than the other group with statistical
      significant difference (76.4 versus 30.6%, p = .000). No difference between side
      effects in both groups (p = .171) Conclusions: Topical application of lidocaine
      prilocaine cream is an effective analgesic during repair of perineal tears with
      no harmful side effects.

PMID- 29334291
TI  - Prevalence and risk factors of hyperprolactinemia among patients with various
      psychiatric diagnoses and medications.
AB  - OBJECTIVES: Hyperprolactinemia is a common adverse event associated with
      psychotropic medications (mainly antipsychotics) used in the management of
      schizophrenia and bipolar disorders. The aim of this study was to estimate the
      prevalence of hyperprolactinemia in psychiatric patients and to evaluate its
      association with various psychiatric diagnoses and the use of various
      psychotropic medications. METHODS: A cross-sectional observational study was
      conducted between July 2012 and June 2014. Patients were recruited from a number
      of hospitals located in the five regions of Saudi Arabia. Hyperprolactinemia was
      defined as blood prolactin levels >25 ng/mL in females and >20 ng/mL in males,
      regardless of the presence of symptoms. RESULTS: A total of 997 patients (553
      males and 444 females) were included in the current analysis. The average blood
      prolactin level was 32.6 +/- 44.1 ng/mL, with higher levels among females than
      males (42.9 +/- 61.3 versus 24.4 +/- 18.6, p < .001). The prevalence of
      hyperprolactinemia was 44.3%, with no significant gender difference (41.9% in
      females versus 46.3% in males, p = .164) but with huge variability according to
      individual antipsychotic and other psychotropic medications. In the multivariate
      analysis adjusted for demographic and clinical characteristics,
      hyperprolactinemia was independently and positively associated with using
      antipsychotic medications (OR = 2.08, 1.26-3.42, p = .004). Additionally,
      previous hospitalisation, diabetes and hypothyroidism were positively associated,
      whereas having primary depressive disorders was negatively associated.
      CONCLUSIONS: We report a high prevalence of hyperprolactinemia among a large
      sample of psychiatric patients in Saudi Arabia, which was linked to the use of
      antipsychotic medications. Routine measurement of blood prolactin levels for all
      patients maintained on antipsychotic agents is recommended, regardless of
      symptoms.

PMID- 29334293
TI  - DNA barcoding for species identification in deep-sea clams (Mollusca: Bivalvia:
      Vesicomyidae).
AB  - Deep-sea clams (Bivalvia: Vesicomyidae) have been found in reduced environments
      over the world oceans, but taxonomy of this group remains confusing at species
      and supraspecific levels due to their high-morphological similarity and
      plasticity. In the present study, we collected mitochondrial COI sequences to
      evaluate the utility of DNA barcoding on identifying vesicomyid species. COI
      dataset identified 56 well-supported putative species/operational taxonomic units
      (OTUs), approximately covering half of the extant vesicomyid species. One species
      (OTU2) was first detected, and may represent a new species. Average distances
      between species ranged from 1.65 to 29.64%, generally higher than average
      intraspecific distances (0-1.41%) when excluding Pliocardia sp.10 cf. venusta
      (average intraspecific distance 1.91%). Local barcoding gap existed in 33 of the
      35 species when comparing distances of maximum interspecific and minimum
      interspecific distances with two exceptions (Abyssogena southwardae and
      Calyptogena rectimargo-starobogatovi). The barcode index number (BIN) system
      determined 41 of the 56 species/OTUs, each with a unique BIN, indicating their
      validity. Three species were found to have two BINs, together with their high
      level of intraspecific variation, implying cryptic diversity within them.
      Although fewer 16 S sequences were collected, similar results were obtained.
      Nineteen putative species were determined and no overlap observed between intra-
      and inter-specific variation. Implications of DNA barcoding for the Vesicomyidae
      taxonomy were then discussed. Findings of this study will provide important
      evidence for taxonomic revision in this problematic clam group, and accelerate
      the discovery of new vesicomyid species in the future.

PMID- 29334294
TI  - Comments on manuscript: early amniotomy after dinoprostone insert used for the
      induction of labor.

PMID- 29334292
TI  - Safety and effectiveness of fascial therapy in adult patients with hemophilic
      arthropathy. A pilot study.
AB  - BACKGROUND: The primary clinical manifestations of hemophilia are muscle and
      joint bleeding. Recurrent bleeding leads to a degenerative process known as
      hemophilic arthropathy. Fascial therapy is one of the most used physiotherapy
      techniques today to improve joint dysfunctions and chronic pain. OBJECTIVE: To
      assess the safety and efficacy of fascial therapy treatment in patients with
      hemophilic arthropathy of ankle and knee. DESIGN: Non-randomized, controlled
      clinical trial. INTERVENTION: Sixteen patients with hemophilia were allocated to
      an experimental group or to a control group. The physiotherapy intervention was
      performed through three sessions (one per week), for 60 min per session. Patients
      received a physiotherapy treatment using a fascial therapy protocol for patients
      with hemophilia. MAIN OUTCOME MEASURES: The joint status was evaluated using the
      Hemophilia Joint Health Score; pain was assessed with the Visual Analogue Scale;
      the range of movement was evaluated using a universal goniometer; the flexibility
      of the hamstring muscles was assessed with the fingertip-to-floor, and the lumbar
      mobility through the Schober test. RESULTS: We observed significant differences
      in the experimental group for both quality of life and illness behavior. There
      was no significant improvement in the joint status; however, an improvement was
      noted in terms of perception of pain in the ankle. CONCLUSIONS: A physiotherapy
      program based on fascial therapy is safe in patients with hemophilia. Fascial
      therapy may improve joint status, pain, and mobility in patients with hemophiliac
      arthropathy of the knee and ankle.

PMID- 29334296
TI  - The experience of hearing loss: journey through aural rehabilitation.

PMID- 29334295
TI  - Neuritin provides neuroprotection against experimental traumatic brain injury in
      rats.
AB  - OBJECTIVES: Traumatic brain injury (TBI) is a leading cause of death and
      disability worldwide. Neuritin is a neurotrophic factor that regulates neural
      growth and development. However, the role of neuritin in alleviating TBI has not
      been investigated. METHODS: In this study, Sprague Dawley rats (n = 144) weighing
      300 +/- 50 g were categorized into control, sham, TBI and TBI + neuritin groups.
      The neurological scores and the ultrastructure of cortical neurons, apoptotic
      cells and caspase-3 were measured by using Garcia scoring system, transmission
      electron microscopy, terminal deoxynucleotidyl transferase-mediated dUTP nick-end
      labeling, Western blot analysis and real-time RT-PCR at various time points post
      TBI. CONCLUSIONS: Our findings indicated that neuritin plays a protective role in
      TBI by improving neurological scores, repairing injured neurons and protecting
      the cortical neurons against apoptosis through inhibition of caspase-3
      expression. Further investigation of the molecular mechanisms underlying caspase
      3 inhibition by neuritin will provide a research avenue for potential TBI
      therapeutics.

PMID- 29334297
TI  - Perceptions of older people's oral health care among nurses working in geriatric
      home care.
AB  - OBJECTIVES: This study investigates nurses' self-reported experiences and
      perceptions of older people's oral health care using a qualitative method.
      METHODS: We interviewed 10 nurses working in geriatric home care who regularly
      visit and take care of older people in their homes. The interviews consisted of
      semi-structured questions. The interviews were then transcribed and analysed.
      RESULTS: All nurses were aware of the connection between oral health and general
      health, but more detailed knowledge about oral health was lacking and confidence
      in oral health care practices was limited. Many of the interviewees noted the
      cleaning of removable dentures and problems related to them, but did not mention
      anything about periodontal diseases. Oral health education among the nurses was
      rare. The nurses reported lack of time to take care of their clients' oral
      health. As possible development steps, the interviewees suggested that including
      oral health care in the daily treatment plan would improve oral health care
      practices. CONCLUSIONS: The nurses' lack of knowledge about oral health care and
      uncertainty in oral health practices among older people are major problems in
      daily geriatric home care. Oral health education and confidence in oral health
      practices should be improved in both basic and on-the-job education.

PMID- 29334298
TI  - Long-term effects of tungsten carbide (WC) nanoparticles in pelagic and benthic
      aquatic ecosystems.
AB  - As the production and usage of nanomaterials are increasing so are the concerns
      related to the release of the material into nature. Tungsten carbide (WC) is
      widely used for its hard metal properties, although its use, in for instance tyre
      studs, may result in nano-sized particles ending up in nature. Here, we evaluate
      the potential long-term exposure effects of WC nanoparticles on a pelagic
      (Daphnia magna) and a benthic (Asellus aquaticus) organism. No long-term effects
      were observed in the benthic system with respect to population dynamics or
      ecosystem services. However, long-term exposure of D. magna resulted in increased
      time to first reproduction and, if the particles were resuspended, strong effects
      on survival and reproductive output. Hence, the considerable differences in acute
      vs. long-term exposure studies revealed here emphasize the need for more long
      term studies if we are to understand the effects of nanoparticles in natural
      systems.

PMID- 29334299
TI  - Mucoadhesive buccal film containing ornidazole and dexamethasone for oral ulcers:
      in vitro and in vivo studies.
AB  - A bilayered mucoadhesive buccal film containing a combination of ornidazole (OD)
      and dexamethasone sodium phosphate (DEX) was prepared using solvent casting to
      treat oral ulcers. Films were systematically evaluated in vitro to obtain the
      optimum formulation. The therapeutic effects of these films were investigated in
      the rabbit oral ulcer model and the in vivo release of OD and DEX in the human
      oral cavity was also evaluated. The backing layer contained ethyl cellulose and
      an optimal mucoadhesive layer containing both OD and DEX was produced. Films from
      the optimum formulation were 0.427 +/- 0.015 mm thick, weighed 55.89 +/- 0.79 mg,
      and had a surface pH of 6.34 +/- 0.01. The drug content of the optimum
      formulation approximated the theoretical value with good uniformity (2.959 +/-
      0.106 mg/cm2 for OD and 0.877 +/- 0.031 mg/cm2 for DEX). The formulation showed
      favorable swelling characteristics and both drugs were released at >95% after 4
      h. Moreover, the compound film had a statistically significant effect on mucosal
      repair and reduced ulcer inflammation without stimulating the human oral mucosa.
      Cmax of OD in saliva was 37.04 MUg/ml and that of DEX was 9.737 MUg/ml. Given
      promising therapeutic effects, the compound film developed here could become a
      local drug delivery device for treating oral ulcers.

PMID- 29334300
TI  - The impact of early molecular response in children and adolescents with chronic
      myeloid leukemia treated with imatinib: a single-center study from China.
AB  - Chronic myeloid leukemia (CML) is rare among children and adolescents. The early
      molecular response (EMR) is an important prognostic significance for adult CML
      patients. This study explored the impact of EMR on the prognosis in 40 children
      and adolescents with CML-CP treated with imatinib (IM). Our results showed that a
      high proportion of patients failed to achieve the BCR-ABL1/ABL1 International
      Scale (IS) <= 10% at 3 months. Children with a BCR-ABL1/ABL1 <= 10% at 3 months
      and <1% at 6 months increased the rate of achieving complete cytogenetic response
      (CCyR) and/or major molecular response (MMR) at 12 months compared to those with
      BCR-ABL1/ABL1 > 10%. With a median follow-up of 42 months, patients with BCR
      ABL1/ABL1 <= 10% showed a better 4-year event-free survival (EFS). In summary,
      achieving BCR-ABL1/ABL1 IS <=10% at 3 months and <1% at 6 months would increase
      the possibility of achieving MMR, CCyR at 12 months and had a better 4-year EFS.
      EMR is a reliable prognosticator for young CML patients treated with IM.

PMID- 29334301
TI  - Navigating social distance in foundational clinical encounters: Understanding
      medical students' early experiences with diverse patients.
AB  - BACKGROUND: Social distance between patients and physicians has been shown to
      affect the quality of care that patients receive. Little is known about how
      social distance between students and patients is experienced by learners during
      early clinical exposures in medical school. OBJECTIVE: This study aims to explore
      students' stories of experiencing social distance with patients with concordant
      and discordant social characteristics as themselves, respectively, as well as
      students' needs from medical curricula regarding developing social competence.
      METHODS: Semi-structured interviews of medical students [n = 16] were performed,
      and a post-interview survey and a visual analog scale were completed. The
      interviews were audio-recorded and transcribed. The written transcripts were
      coded using the constant comparison method and analyzed for emerging themes.
      RESULTS: Students experience social distance with patients; yet, they are not
      taught explicitly by their preceptors how to manage these experiences. Students
      identified their needs for the curriculum in regard to developing social
      competence and proposed various strategies and curriculum recommendations.
      CONCLUSIONS: Our results support that students believe that social competence
      training is important for their professional development to improve relationship
      building with diverse patients. As such, it would be valuable to incorporate
      student recommendations in the formation of a social competence curriculum.

PMID- 29334302
TI  - miRNAs as potential regulators of mTOR pathway in renal cell carcinoma.
AB  - Renal cell carcinoma (RCC) is the most commonly occurring solid cancer of the
      adult kidney with the majority of RCC cases being detected accidentally. The most
      aggressive subtype is clear cell RCC (ccRCC). miRNAs, a family of small noncoding
      RNAs regulating gene expression have been identified as key biological
      modulators. The von Hippel-Lindau pathway is one of the signaling pathways
      involved in the pathophysiology of ccRCC. Another oncogenic mechanism involves
      the activation of PI3K/AKT/mTOR signaling and serves as a central regulator of
      cell metabolism, proliferation and survival. Several studies have described the
      involvement of miRNA dysregulation in the pathogenesis and progression of ccRCC.
      These molecules can be considered as potential diagnostic and prognostic
      biomarkers, allowing response to therapy to be monitored.

PMID- 29334303
TI  - Enteral l-arginine supplementation for prevention of necrotizing enterocolitis in
      premature infants.

PMID- 29334304
TI  - Switching from laparoscopic radical prostatectomy to robot assisted laparoscopic
      prostatectomy: comparing oncological outcomes and complications.
AB  - OBJECTIVES: To compare oncological outcomes and complication rates based on the
      Clavien classification between laparoscopic radical prostatectomies (LRP) and
      robot-assisted laparoscopic radical prostatectomies (RALP). MATERIAL AND METHODS:
      In a prospective quality registry clinical data were consecutively entered for
      544 LRP and 1081 RALP patients operated from 2003 to the end of 2012.
      Complications within 90 days postoperatively were assessed according to the
      Clavien classification and compared between LRP and RALP patients. Univariate and
      multivariate analyses of logistic regression were used to fit oncological
      outcomes and complication data. RESULTS: The mean operation time was 213 and 135
      minutes in LRP and RALP patients, respectively. Pathological T3a stage (pT3a) in
      the RALP group was more frequent than in the LRP group, 32.4% versus 17.8%,
      respectively. For pT2 tumours, positive surgical margins (PSM) rate for LRP and
      RALP, was 20.3% vs 10.6%, respectively (p < .001). In the LRP group 74 patients
      (13.6%) reported 104 and in the RALP group 141 patients (13.0%) reported 177
      complications (p = .75). Seventeen (3.1%) LRP patients and 15 (1.4%) RALP
      patients had Clavien grade IIIb complications (p = .017). Surgical reintervention
      was necessary in 14 patients (2.6%) and 17 patients (1.6%) in the LRP and RALP
      group, respectively (p = .04). CONCLUSION: Switching from LRP to RALP resulted in
      a much shorter operation time without compromising oncological outcome. There was
      no statistically significant difference in overall complication-rates between LRP
      and RALP. However, LRP patients had more serious complications and increased need
      for surgical reintervention compared to RALP patients.

PMID- 29334305
TI  - Twelve tips for teaching a comprehensive disease-focused course with a global
      perspective: A sickle cell disease example.
AB  - A disease-focused course entitled "Understanding Sickle Cell Disease: A
      Biopsychosocial Approach" addressed the complex nature of SCD using patient
      centered, global and interdisciplinary approaches. Sickle cell disease (SCD) is a
      rare inherited blood disorder that requires multidisciplinary care. Worldwide 20
      25 million individuals have SCD, which is associated with a shortened lifespan
      due to many medical complications and social and behavioral health challenges.
      Health care professionals often have limited knowledge of SCD as they typically
      learn about it within the context of their own disciplines. This article provides
      twelve tips for educators that can be used to develop a similar course on any
      disease, with considerations for both low- and high-resource countries. The tips
      were devised from personal experience and available literature. Through these
      twelve tips, we provide a practical framework for increasing knowledge of complex
      diseases like SCD using a comprehensive elective course.

PMID- 29334306
TI  - Learning science as a potential new source of understanding and improvement for
      continuing education and continuing professional development.
AB  - Learning science is an emerging interdisciplinary field that offers educators key
      insights about what happens in the brain when learning occurs. In addition to
      explanations about the learning process, which includes memory and involves
      different parts of the brain, learning science offers effective strategies to
      inform the planning and implementation of activities and programs in continuing
      education and continuing professional development. This article provides a brief
      description of learning, including the three key steps of encoding, consolidation
      and retrieval. The article also introduces four major learning-science
      strategies, known as distributed learning, retrieval practice, interleaving, and
      elaboration, which share the importance of considerable practice. Finally, the
      article describes how learning science aligns with the general findings from the
      most recent synthesis of systematic reviews about the effectiveness of continuing
      medical education.

PMID- 29334308
TI  - Neuromuscular degenerative effects of Ankaferd Blood Stopper(r) in mouse sciatic
      nerve model.
AB  - PURPOSE: Ankaferd Blood Stopper(r) (ABS), a licenced medicinal herbal extract, is
      commonly used as an effective topical haemostatic agent. This study is designed
      to investigate whether topical ABS application may cause peripheral nerve
      degeneration and neuromuscular dysfunction in a mouse sciatic nerve model.
      METHODS: Twenty mice were randomly divided into two groups; an ABS treated
      experimental group and a saline-treated control group. Left sciatic nerves were
      treated with 0.3 ml of ABS in the experimental group and 0.3 ml of sterile saline
      in the control group for 5 min. Peripheral nerve degeneration and neuromuscular
      dysfunction were evaluated by behavioural tests, electrophysiological analysis
      and weight ratio comparison of target muscles. RESULTS: The motor function,
      assessed by the sciatic function index, was significantly impaired in ABS-treated
      animals as compared to the animals treated with saline. Motor coordination,
      evaluated with the rotarod test, was significantly decreased (-42%) in ABS
      treated animals compared to the saline-treated animals. The degree of pain,
      assessed by the reaction latency to thermal stimuli (hot-plate test), was
      significantly prolonged (313%) in ABS-treated mice when compared to the saline
      treated mice. ABS-treated mice showed a significant reduction in motor nerve
      conduction velocity (MNCV) (-52%) and the compound muscle action potential (CMAP)
      (-47%); however, it significantly prolonged onset latency (23%). The
      gastrocnemius muscles weight ratio of the ABS group was considerably lower than
      that of the control group. CONCLUSIONS: These findings demonstrate that ABS
      triggers peripheral nerve degeneration and functional impairment and, thus
      promotes a deterioration of sciatic nerves.

PMID- 29334307
TI  - Regorafenib regresses an imatinib-resistant recurrent gastrointestinal stromal
      tumor (GIST) with a mutation in exons 11 and 17 of c-kit in a patient-derived
      orthotopic xenograft (PDOX) nude mouse model.
AB  - Gastrointestinal stromal tumor (GIST) with a mutation in exons 11 and 17 of c-kit
      is a rare type of sarcoma. The aim of this study was to determine drug
      sensitivity for a regionally-recurrent case of GIST using a patient-derived
      orthotopic xenograft (PDOX) model. The PDOX model was established in the anterior
      wall of the stomach. GIST PDOX models were randomized into 5 groups of 6 mice
      each when the tumor volume reached 60 mm3: G1, control group; G2, imatinib group
      (oral administration (p.o.), daily, for 3 weeks); G3, sunitinib group (p.o.,
      daily, for 3 weeks); G4, regorafenib (p.o., daily, for 3 weeks); G5, pazopanib
      (p.o., daily, for 3 weeks). All mice were sacrificed on day 22. Tumor volume was
      evaluated on day 0 and day 22 by laparotomy. Body weight were measured 2 times
      per week. Though regorafenib is third-line therapy for GIST, it was the most
      effective drug and regressed the tumor significantly (p < 0.001). Sunitinib
      suppressed tumor growth compared to the control group (p = 0.002). Imatinib,
      first-line therapy for GIST, and pazopanib did not have significant efficacy
      compared to the control group (p = 0.886, p = 0.766). The implications of this
      result is discussed for GIST patients.

PMID- 29334309
TI  - Effects of resisted sprint training on sprinting ability and change of direction
      speed in professional soccer players.
AB  - Resisted sprint training consists of performing overloaded sprints, which may
      produce greater effects than traditional sprint training. We compared a resisted
      sprint training with overload control versus an unresisted sprint training
      program on performance in soccer players. Eighteen elite athletes were randomly
      assigned to resisted (RST) or unresisted sprint training protocol (UR). Before
      and after a 6-week training period, sprinting ability, change of direction speed
      (COD), vertical jumps (SJ and CMJ), mean power (MP) and mean propulsive power
      (MPP) at distinct loads were assessed. Both groups improved sprinting ability at
      all distances evaluated (5m: UR = 8%, RST = 7%; 10m: UR = 5%, RST = 5%; 15m: UR =
      4%, RST = 4%; 20m: UR = 3%, RST = 3%; 25m: UR = 2%, RST = 3%;), COD (UR = 6%; RST
      = 6%), SJ (UR = 15%; RST = 13%) and CMJ (UR = 15%; RST = 15%). Additionally, both
      groups increased MP and MPP at all loads evaluated. The between-group magnitude
      based inference analysis demonstrated comparable improvement ("trivial" effect)
      in all variables tested. Finally, our findings support the effectiveness of a
      short-term training program involving squat jump exercise plus sprinting
      exercises to improve the performance of soccer players.

PMID- 29334310
TI  - Dendritic polyglycerol nanoparticles show charge dependent bio-distribution in
      early human placental explants and reduce hCG secretion.
AB  - A thorough understanding of nanoparticle bio-distribution at the feto-maternal
      interface will be a prerequisite for their diagnostic or therapeutic application
      in women of childbearing age and for teratologic risk assessment. Therefore, the
      tissue interaction of biocompatible dendritic polyglycerol nanoparticles (dPG
      NPs) with first- trimester human placental explants were analyzed and compared to
      less sophisticated trophoblast-cell based models. First-trimester human placental
      explants, BeWo cells and primary trophoblast cells from human term placenta were
      exposed to fluorescence labeled, ~5 nm dPG-NPs, with differently charged
      surfaces, at concentrations of 1 uM and 10 nM, for 6 and 24 h. Accumulation of
      dPGs was visualized by fluorescence microscopy. To assess the impact of dPG-NP on
      trophoblast integrity and endocrine function, LDH, and hCG releases were
      measured. A dose- and charge-dependent accumulation of dPG-NPs was observed at
      the early placental barrier and in cell lines, with positive dPG-NP-surface
      causing deposits even in the mesenchymal core of the placental villi. No signs of
      plasma membrane damage could be detected. After 24 h we observed a significant
      reduction of hCG secretion in placental explants, without significant changes in
      trophoblast apoptosis, at low concentrations of charged dPG-NPs. In conclusion,
      dPG-NP's surface charge substantially influences their bio-distribution at the
      feto-maternal interface, with positive charge facilitating trans-trophoblast
      passage, and in contrast to more artificial models, the first-trimester placental
      explant culture model reveals potentially hazardous influences of charged dPG-NPs
      on early placental physiology.

PMID- 29334311
TI  - The surface chemistry determines the spatio-temporal interaction dynamics of
      quantum dots in atherosclerotic lesions.
AB  - AIM: To optimize the design of nanoparticles for diagnosis or therapy of vascular
      diseases, it is mandatory to characterize the determinants of nano-bio
      interactions in vascular lesions. MATERIALS & METHODS: Using ex vivo and in vivo
      microscopy, we analyzed the interactive behavior of quantum dots with different
      surface functionalizations in atherosclerotic lesions of ApoE-deficient mice.
      RESULTS: We demonstrate that quantum dots with different surface
      functionalizations exhibit specific interactive behaviors with distinct molecular
      and cellular components of the injured vessel wall. Moreover, we show a role for
      fibrinogen in the regulation of the spatio-temporal interaction dynamics in
      atherosclerotic lesions. CONCLUSION: Our findings emphasize the relevance of
      surface chemistry-driven nano-bio interactions on the differential in vivo
      behavior of nanoparticles in diseased tissue.

PMID- 29334312
TI  - Targeting of phospho-eIF4E by homoharringtonine eradicates a distinct subset of
      human acute myeloid leukemia.
AB  - More than half of the patients with acute myeloid leukemia (AML) fail to achieve
      long-term disease-free survival with current therapies and novel therapeutic
      strategies are urgently needed. The effects of homoharringtonine (HHT) on the
      growth of AML cell lines and primary leukemia cells were examined using MTT,
      colony formation assay. The effects of HHT on both eukaryotic translation
      initiation factor 4E (eIF4E) and phospho-eIF4E(p-eIF4E) were examined through
      western blot and immunofluorescence staining. HHT selectively reduced levels of p
      eIF4E and its downstream oncoprotein Mcl-1, and potently inhibited in vitro and
      in vivo the growth of a distinct subset of AML cells and primary leukemia cells
      expressing high level of p-eIF4E through apoptosis. Our findings suggest that HHT
      might be a first-in-class p-eIF4E-targeted drug and offer a novel therapeutic
      option for AML patients expressing high level of p-eIF4E.

PMID- 29334314
TI  - On the intrinsic constraint of bacterial growth rate: M. tuberculosis's view of
      the protein translation capacity.
AB  - In nature, the maximal growth rates vary widely among different bacteria species.
      Fast-growing bacteria species such as Escherichia coli can have a shortest
      generation time of 20 min. Slow-growing bacteria species are perhaps best known
      for Mycobacterium tuberculosis, a human pathogen with a generation time being no
      less than 16 h. Despite of the significant progress made on understanding the
      pathogenesis of M. tuberculosis, we know little on the origin of its intriguingly
      slow growth. From a global view, the intrinsic constraint of the maximal growth
      rate of bacteria remains to be a fundamental question in microbiology. In this
      review, we analyze and discuss this issue from the angle of protein translation
      capacity, which is the major demand for cell growth. Based on quantitative
      analysis, we propose four parameters: rRNA chain elongation rate, abundance of
      RNA polymerase engaged in rRNA synthesis, polypeptide chain elongation rate, and
      active ribosome fraction, which potentially limit the maximal growth rate of
      bacteria. We further discuss the relation of these parameters with the growth
      rate for M. tuberculosis as well as other bacterial species. We highlight future
      comprehensive investigation of these parameters for different bacteria species to
      understand how bacteria set their own specific growth rates.

PMID- 29334313
TI  - Pneumonia infection in mice reveals the involvement of the feoA gene in the
      pathogenesis of Acinetobacter baumannii.
AB  - Acinetobacter baumannii has emerged in the last decade as an important nosocomial
      pathogen. To identify genes involved in the course of a pneumonia infection, gene
      expression profiles were obtained from A. baumannii ATCC 17978 grown in mouse
      infected lungs and in culture medium. Gene expression analysis allowed us to
      determine a gene, the A1S_0242 gene (feoA), over-expressed during the pneumonia
      infection. In the present work, we evaluate the role of this gene, involved in
      iron uptake. The inactivation of the A1S_0242 gene resulted in an increase
      susceptibility to oxidative stress and a decrease in biofilm formation, in
      adherence to A549 cells and in fitness. In addition, infection of G. mellonella
      and pneumonia in mice showed that the virulence of the Delta0242 mutant was
      significantly attenuated. Data presented in this work indicated that the A1S_0242
      gene from A. baumannii ATCC 17978 strain plays a role in fitness, adhesion,
      biofilm formation, growth, and, definitively, in virulence. Taken together, these
      observations show the implication of the feoA gene plays in the pathogenesis of
      A. baumannii and highlight its value as a potential therapeutic target.

PMID- 29334315
TI  - Interplay between p53 and Ink4c in spermatogenesis and fertility.
AB  - The tumor suppressor p53, and the cyclin-dependent kinase inhibitor Ink4c, have
      been both implicated in spermatogenesis control. Both p53-/- and Ink4c-/- single
      knockout male mice are fertile, despite testicular hypertrophy, Leydig cell
      differentiation defect, and increased sperm count in Ink4c-/- males. To
      investigate their collaborative roles, we studied p53-/- Ink4c-/- dual knockout
      animals, and found that male p53-/- Ink4c-/- mice have profoundly reduced
      fertility. Dual knockout male mice show a marked decrease in sperm count,
      abnormal sperm morphology and motility, prolongation of spermatozoa proliferation
      and delay of meiosis entry, and accumulation of DNA damage. Genetic studies
      showed that the effects of p53 loss on fertility are independent of its
      downstream effector Cdkn1a. Absence of p53 also partially reverses the
      hyperplasia seen upon Ink4c loss, and normalizes the Leydig cell differentiation
      defect. These results implicate p53 in mitigating both the delayed entry into
      meiosis and the secondary apoptotic response that occur in the absence of Ink4c.
      We conclude that the cell cycle genes p53 and Ink4c collaborate in sperm cell
      development and differentiation, and may be important candidates to investigate
      in human male infertility conditions.

PMID- 29334316
TI  - Potential therapeutic and economic value of risk-stratified treatment as initial
      treatment of multiple myeloma in Europe.
AB  - Biomarkers associated with prognosis in multiple myeloma (MM) can be used to
      stratify patients into risk categories. An attractive alternative to uniform
      treatment (UT), risk-stratified treatment (RST) is proposed where high-risk
      patients receive bortezomib-based regimens while standard-risk patients receive
      alternative less costly regimens. An early Markov-type decision analytic model
      evaluated the potential therapeutic and economic value of different RST
      strategies compared with UT in MM patients in key European countries. Results
      suggest RST strategies were both cheaper and more effective than UT across all
      countries, with the molecular marker-only strategy RST-SKY92 producing maximum
      health gains (0.031-0.039 QALYs). The conclusions remained consistent in the
      univariate sensitivity analyses. These findings should encourage stakeholders to
      support the adoption of RST approaches in MM.

PMID- 29334317
TI  - Fluctuation - a common but neglected pattern of physical activity behaviour: An
      exploratory review of studies in recent 20 years.
AB  - BACKGROUND: Regular physical activity (PA) is beneficial for physical and
      psychological well-being, yet many people do not achieve these health benefits
      due to irregular PA participation which is also known as fluctuation. Limited
      attention has been given to the phenomenon of fluctuation in the PA behaviour
      literature. OBJECTIVE: The aim of this review was to explore and to map
      definitions, measurements, behavioural evidence, and factors related to PA
      fluctuation. METHODS: Eligible studies were initially identified by a systematic
      search of articles conducted in four databases: Scopus, PubMed, PsycINFO, and
      SPORTDiscus between January 1996 and March 2016. Inclusion and exclusion criteria
      were set to check the eligibility of all articles. Additional articles were
      included by manual searching and expert recommendation. RESULTS: Fifteen articles
      were finally included. Definitions of fluctuation are understood from two
      perspectives, either as a stage in the process of behaviour change, or as a
      particular PA phenomenon consisting of lapse and readoption. Common features were
      extracted: behavioural irregularity, high risk of drop-out, intention and
      readiness for PA, low automaticity, and limited self-regulation. Furthermore,
      fluctuation identification was summarised in three approaches such as stage
      algorithm, self-identified PA lapse and readoption, and prospective within-person
      variation in meeting the PA guidelines. Regarding the empirical evidence, this
      review found that people in PA fluctuation were significantly distinct from those
      in preparation and maintenance of PA behavioural performance, as well as distinct
      in psychosocial features. CONCLUSIONS: Notwithstanding the limitations, this
      review has provided valuable insight into the phenomenon of PA fluctuation.

PMID- 29334318
TI  - Molecular dynamics perspective on the thermal stability of mandelate racemase.
AB  - Mandelate racemase from Pseudomonas putida is a promising candidate for the
      dynamic kinetic resolution of alpha-hydroxy carboxylic acids. In the present
      study, the thermal stability of mandelate racemase was investigated through
      molecular dynamics simulations in the temperature range of 303-363 K, which can
      guide the design of mandelate racemase with higher stability. The basic features
      such as radius of gyration, surface accessibility, and secondary structure
      content suggested the instability of mandelate racemase at high temperatures.
      With increase in temperature, alpha-helix content reduced significantly,
      especially the alpha-helices exposed to the environment. At the simulation time
      scale considered, intra-protein hydrogen bonds, hydrogen bonds between protein
      and water decreased at 363 K, while the number of salt-bridges increased. The
      long-distance networks remarkably changed at 363 K. A considerable number of long
      lived (percentage existence time higher than 90%) hydrogen bonds and Calpha
      contacts were lost. Root mean square fluctuation analysis revealed regions with
      high fluctuation, which should be helpful in the reengineering of mandelate
      racemase for enhanced thermal stability.

PMID- 29334319
TI  - Effect of Porphyromonas gingivalis infection in the placenta and umbilical cord
      in pregnant mice with low birth weight.
AB  - OBJECTIVE: Growing evidence indicates an association between periodontitis and
      delivery outcome; however, the mechanism is unclear. This study aimed to
      investigate the influence of Porphyromonas gingivalis (Pg) infection on delivery
      outcome in mice. MATERIALS AND METHODS: Bacteremia was induced in pregnant
      Slc:ICR mice (8 weeks old) by intravenous injection of Pg. Mice were randomly
      divided into a control group (CO), and those receiving Pg injection at
      gestational day 1 (GD1), gestational day 15 (GD15) or every day (ED). Delivery
      outcome, Pg infection, and gene expression in the placenta and umbilical cord
      were evaluated. RESULTS: Birth weight was lower in the ED and GD15 groups than in
      the CO group. A remarkable increase in anti-Pg IgG antibody was observed in the
      ED and GD1 groups, although Pg was not detected in the placenta or umbilical
      cord. mRNA expression of Tnfalpha and Il6 in the placenta, and Hif1alpha in the
      umbilical cord, was significantly increased in the ED group. Microarray analysis
      of the umbilical cord revealed increased expression of several genes including
      Orm1, Mgl2, Rps6ka3 and Trim15 in the ED group. CONCLUSIONS: Pg infection during
      the third trimester caused low birth weight and inflammation in the placenta and
      umbilical cord.

PMID- 29334320
TI  - Human dopamine transporter: the first implementation of a combined in silico/in
      vitro approach revealing the substrate and inhibitor specificities.
AB  - Parkinson's disease (PD) is characterized by the loss of dopamine-generating
      neurons in the substantia nigra and corpus striatum. Current treatments alleviate
      PD symptoms rather than exerting neuroprotective effect on dopaminergic neurons.
      New drugs targeting the dopaminergic neurons by specific uptake through the human
      dopamine transporter (hDAT) could represent a viable strategy for establishing
      selective neuroprotection. Molecules able to increase the bioactive amount of
      extracellular dopamine, thereby enhancing and compensating a loss of dopaminergic
      neurotransmission, and to exert neuroprotective response because of their
      accumulation in the cytoplasm, are required. By means of homology modeling,
      molecular docking, and molecular dynamics simulations, we have generated 3D
      structure models of hDAT in complex with substrate and inhibitors. Our results
      clearly reveal differences in binding affinity of these compounds to the hDAT in
      the open and closed conformations, critical for future drug design. The
      established in silico approach allowed the identification of promising substrate
      compounds that were subsequently analyzed for their efficiency in inhibiting hDAT
      dependent fluorescent substrate uptake, through in vitro live cell imaging
      experiments. Taken together, our work presents the first implementation of a
      combined in silico/in vitro approach enabling the selection of promising
      dopaminergic neuron-specific substrates.

PMID- 29334321
TI  - Biosynthesis of galactomannans found in filamentous fungi belonging to
      Pezizomycotina.
AB  - The galactomannans (GMs) that are produced by filamentous fungi belonging to
      Pezizomycotina, many of which are pathogenic for animals and plants, are
      polysaccharides consisting of alpha-(1->2)-/alpha-(1->6)-mannosyl and beta-(1->5)
      /beta-(1->6)-galactofuranosyl residues. GMs are located at the outermost layer of
      the cell wall. When a pathogenic fungus infects a host, its cell surface must be
      in contact with the host. The GMs on the cell surface may be involved in the
      infection mechanism of a pathogenic fungus or the defense mechanism of a host.
      There are two types of GMs in filamentous fungi, fungal-type galactomannans and O
      mannose type galactomannans. Recent biochemical and genetic advances have
      facilitated a better understanding of the biosynthesis of both types. This review
      summarizes our current information on their biosynthesis.

PMID- 29334322
TI  - Plasma brain-derived neurotrophic factor (pBDNF) and executive dysfunctions in
      patients with major depressive disorder.
AB  - OBJECTIVES: Executive dysfunctions are frequently seen in patients with major
      depressive disorder (MDD) and normalise in many cases during effective
      antidepressant therapy. This study investigated whether a normalisation of
      executive dysfunctions during antidepressant treatment correlates with or can be
      predicted by clinical parameters or levels of brain-derived neurotrophic factor
      (BDNF). METHODS: In 110 MDD patients with executive dysfunctions (percentile
      <16), executive functions and plasma BDNF levels were analysed at baseline, and
      days 14 and 56 of an antidepressant treatment. BDNF exon IV and P11 methylation
      status was studied at baseline. RESULTS: Eighty patients (73%) experienced a
      normalisation of executive dysfunctions, while 30 (27%) suffered from persistent
      dysfunctions until day 56. Patients with persistent dysfunctions had
      significantly higher HAMD scores at days 14 and 56, and lower plasma BDNF levels
      at each time point than patients with a normalisation of dysfunctions (F1= 10.18;
      P = 0.002). This was seen for verbal fluency, but not processing speed. BDNF exon
      IV and p11 promoter methylation was not associated with test performance.
      CONCLUSIONS: Our results corroborate a concomitant amelioration of executive
      dysfunctions with successful antidepressant therapy and support a role of BDNF in
      the neural mechanisms underlying the normalisation of executive dysfunctions in
      MDD. ClinicalTrials.gov number: NCT00974155; EudraCT: 2008-008280-96.

PMID- 29334323
TI  - Development of functional agricultural products utilizing the new health claim
      labeling system in Japan.
AB  - In April 2015, Consumer Affairs Agency of Japan launched a new food labeling
      system known as "Foods with Function Claims (FFC)." Under this system, the food
      industry independently evaluates scientific evidence on foods and describes their
      functional properties. As of May 23, 2017, 1023 FFC containing 8 fresh foods have
      been launched. Meanwhile, to clarify the health-promoting effects of agricultural
      products, National Agriculture and Food Research Organization (NARO) implemented
      the "Research Project on Development of Agricultural Products" and demonstrated
      the risk reduction of osteoporosis of beta-cryptoxanthin rich Satsuma mandarins
      and the anti-allergic effect of the O-methylated catechin rich tea cultivar
      Benifuuki. These foods were subsequently released as FFC. Moreover, NARO
      elucidated the health-promoting effects of various functional agricultural
      products (beta-glucan rich barley, beta-conglycinin rich soybean, quercetin rich
      onion, etc.) and a healthy boxed lunch. This review focuses on new food labeling
      system or research examining functional aspects of agricultural products.

PMID- 29334324
TI  - The rite of passage of becoming a humanitarian health worker: experiences of
      retention in Sweden.
AB  - BACKGROUND: Low retention of humanitarian workers poses constraints on
      humanitarian organisations' capacity to respond effectively to disasters.
      Research has focused on reasons for humanitarian workers leaving the sector, but
      little is known about the factors that can elucidate long-term commitment.
      OBJECTIVE: To understand what motivates and supports experienced humanitarian
      health workers to remain in the sector. METHODS: Semi-structured interviews were
      conducted with 10 experienced nurses who had been on at least three field
      missions with Medecins Sans Frontieres Sweden. Interviews explored factors
      influencing the decision to go on missions, how nurses were supported and how
      they looked back on those experiences. Transcripts were analysed through content
      analysis informed by van Gennep's concept of 'Rite of Passage', combined with
      elements of the self-determination theory. RESULTS: The findings indicate that
      their motivations and how nurses thought of themselves, as individuals and
      professionals, changed over time. For initiation and continued engagement in
      humanitarian work, participants were motivated by several personal and
      professional ambitions, as well as altruistic principles of helping others. When
      starting their first humanitarian missions, nurses felt vulnerable and had low
      self-esteem. However, through experiencing feelings of autonomy, competence and
      relatedness during missions, they underwent a process of change and gradually
      adjusted to new roles as humanitarian health workers. Reintegration in their home
      community, while maintaining the new roles and skills from the missions, proved
      very challenging. They individually found their own ways of overcoming the lack
      of social support they experienced after missions in order to sustain their
      continuation in the sector. CONCLUSIONS: The findings highlight the importance of
      social environments that facilitate and support the adjustment of individuals
      during and after field missions. Learning from positive examples, such as nurses
      with several years of experience, can strengthen strategies of retention, which
      can ultimately improve the delivery of humanitarian assistance.

PMID- 29334325
TI  - Concurrent validity and reliability of torso-worn inertial measurement unit for
      jump power and height estimation.
AB  - The purpose of the present study was to evaluate the concurrent validity and test
      retest repeatability of torso-worn IMU-derived power and jump height in a counter
      movement jump test. Twenty-seven healthy recreationally active males (age, 21.9
      [SD 2.0] y, height, 1.76 [0.7] m, mass, 73.7 [10.3] kg) wore an IMU and completed
      three counter-movement jumps a week apart. A force platform and a 3D motion
      analysis system were used to concurrently measure the jumps and subsequently
      derive power and jump height (based on take-off velocity and flight time). The
      IMU significantly overestimated power (mean difference = 7.3 W/kg; P < 0.001)
      compared to force-platform-derived power but good correspondence between methods
      was observed (Intra-class correlation coefficient [ICC] = 0.69). IMU-derived
      power exhibited good reliability (ICC = 0.67). Velocity-derived jump heights
      exhibited poorer concurrent validity (ICC = 0.72 to 0.78) and repeatability (ICC
      = 0.68) than flight-time-derived jump heights, which exhibited excellent validity
      (ICC = 0.93 to 0.96) and reliability (ICC = 0.91). Since jump height and power
      are closely related, and flight-time-derived jump height exhibits excellent
      concurrent validity and reliability, flight-time-derived jump height could
      provide a more desirable measure compared to power when assessing athletic
      performance in a counter-movement jump with IMUs.

PMID- 29334326
TI  - Predicting the dopamine D2 receptor occupancy of ropinirole in rats using
      positron emission tomography and pharmacokinetic-pharmacodynamic modeling.
AB  - 1. The purpose of this study was to measure dopamine D2/3 receptor occupancy (RO)
      as a marker of the clinical efficacy of ropinirole in rats via positron emission
      tomography (PET) using 18F-fallypride as the radiotracer and to explore the
      relationship between dopamine RO and the plasma concentration of ropinirole via
      pharmacokinetic-pharmacodynamic modeling. 2. Plasma was collected from 16 rats
      treated with one of four doses of ropinirole. For the time-dependent study, the
      data of 16 rats in the 15 mg/kg dose group at four time points were averaged, and
      another 24 rats were divided into three dose groups (5 mg/kg, 30 mg/kg and 60
      mg/kg) for the dose-dependent study; the animals were assessed via 18F-fallypride
      PET scans. The correlation between dopamine RO and the ropinirole plasma
      concentration was investigated, and a pharmacokinetic-pharmacodynamic (PK-PD)
      model was established with WinNonlin 6.3 software. Both the plasma concentration
      and the binding potential changed in a time- and dose-dependent manner, and the
      plasma concentration that induces 50% RO (EC50) as calculated by the PK-PD model
      was 1391 ng/mL. 3. 18F-fallypride appeared to be a suitable radiotracer for
      ropinirole imaging, and its binding to the dopamine D2 receptor has time- and
      concentration-dependent characteristics. A theory-based PK-PD model was developed
      to describe the relationship between the plasma ropinirole concentration and RO,
      providing a methodological foundation for noninvasive and in vivo clinical
      evaluations of ropinirole treatment.

PMID- 29334327
TI  - Migration of a Kirschner wire into the spinal cord: A case report and literature
      review.
AB  - CONTEXT: A Kirschner wire (K-wire) is a stainless steel pin with at least one
      sharpened tip that is mainly used for the internal fixation of bone fractures.
      While some cases of K-wire dislocation and migration have been reported as
      complications after fracture surgery, the intraspinal migration of a K-wire is
      rare. Herein, we report a case in which a K-wire used for sternal fixation 7
      years earlier migrated into the spinal canal. FINDINGS: A 68-year-old male
      suddenly sustained severe radiating pain and numbness in his left upper
      extremity, and walked to our hospital. He had mild weakness in the left wrist
      extensor muscles and the left extensor digitorum. CT-myelography revealed a K
      wire penetrating into the spinal cord at C5-6. There was no injury of the
      trachea, esophagus, or blood vessels. The patient had a history of surgical
      infection after cardiovascular surgery seven years before, and had undergone
      surgical debridement and sternum fixation with two K-wires. One K-wire had
      broken, and part of it migrated upward. Using an anterior approach, we detected
      the tip of K-wire below the left sternocleidomastoid muscle. We cut the K-wire
      into 1 to 2-cm pieces and removed it piece by piece. His postoperative course was
      uneventful and the symptoms improved markedly after the surgery. CONCLUSION: This
      is the first report of a K-wire that had been used for sternal fixation migrating
      into the spinal cord. This case illustrates that although rare, it is possible
      for a K-wire to migrate upward after sternal fixation.

PMID- 29334328
TI  - Different durations within the method of best practice affect the parameters of
      the speed-duration relationship.
AB  - The aim of the study was to determine whether estimates of the speed-duration
      relationship are affected using different time-trial (TT) field-based testing
      protocols, where exhaustive times were located within the generally recommended
      durations of 2-15 min. Ten triathletes (mean +/- SD age: 31.0 +/- 5.7 years;
      height: 1.81 +/- 0.05 m; body mass: 76.5 +/- 6.8 kg) performed two randomly
      assigned field tests to determine critical speed (CS) and the total distance
      covered above CS (D). CS and D were obtained using two different protocols
      comprising three TT that were interspersed by 60 min passive rest. The TTs were
      12, 7, and 3 min in Protocol I and 10, 5, and 2 min in Protocol II. A linear
      relationship of speed vs. the inverse of time (s = D * 1/t + CS) was used to
      determine parameter estimates. Significant differences were found for CS (p =
      0.026), but not for D (p = 0.123). The effect size for CS (d = 0.305) was
      considered small, while that for D was considered moderate (d = 0.742). CS was
      significantly correlated between protocols (r = 0.934; p < 0.001), however, no
      correlation was found for D (r = 0.053; p = 0.884). The 95% limits of agreement
      were +/-0.28m s-1 and +/-73.9 m for CS and D, respectively. These findings
      demonstrate that the choice of exhaustive times within commonly accepted
      durations results in different estimates of CS and D, and thus protocols cannot
      be used interchangeably. The use of a consistent protocol is therefore
      recommended, when investigating or monitoring the speed-duration relationship
      estimates in well-trained athletes.

PMID- 29334329
TI  - Predictive value of metabolic syndrome definitions in patients with myocardial
      infarction with ST segment elevation - are they all the same?
AB  - OBJECTIVES: We sought to determine the predictive power of metabolic syndrome
      (MS) definitions on the prognosis in patients with myocardial infarction with ST
      segment elevation (STEMI). METHODS: We prospectively included 507 patients with
      STEMI who were admitted for primary percutaneous coronary intervention and could
      be identified for MS using the AHA-NHLBI, NCEP-ATP III and IDF definitions. After
      applying these criteria, we divided the group in patients with MS and without MS;
      we compared baseline characteristics, clinical findings and outcomes among these
      patients. RESULTS: The prevalence of MS was lowest with the NCEP-ATP III
      definition (37.87%), followed by the AHA-NHLBI definition (42.80%) and highest
      when using the IDF definition (44.38%). During follow-up, the occurrence of new
      myocardial infarction and new revascularization was significantly higher in
      patients with MS. Only in a group of patients with MS according to the NCEP-ATP
      III definition, a higher number of strokes were recorded. Multivariate analysis
      shows that MS according to the NCEP-ATP III definition was an independent
      predictor for MACE (OR 1.830, 95% CI 1.238-2.704, p = .002) but not for
      mortality. CONCLUSION: Metabolic syndrome according to the NCEP-ATP III
      definition was associated with increased risk of the development of new
      cardiovascular events among the patients with STEMI.

PMID- 29334330
TI  - The presence of free d-aspartate in marine macroalgae is restricted to the
      Sargassaceae family.
AB  - The presence of d-aspartate (d-Asp), a biologically rare amino acid, was
      evaluated in 38 species of marine macroalgae (seaweeds). Despite the ubiquitous
      presence of free l-Asp, free d-Asp was detected in only 5 species belonging to
      the Sargassaceae family of class Phaeophyceae (brown algae) but not in any
      species of the phyla Chlorophyta (green algae) and Rhodophyta (red algae). All
      other members of Phaeophyceae, including 3 species classified into the section
      Teretia of Sargassaceae did not contain d-Asp. These results indicate that the
      presence of free d-Asp in marine macroalgae is restricted only to the
      Sargassaceae family, excluding the species in the section Teretia.

PMID- 29334331
TI  - Transport mobility 5 years after stroke in an urban setting.
AB  - Background People after stroke may have residual problems with mobility that can
      affect their independence and mode of transport. However, there is limited
      knowledge about transport mobility several years after stroke. Objective The
      objective was to survey the outdoor mobility and transportation in an urban
      setting five years post-stroke. Method This cross-sectional study was based on a
      mail survey focusing on long-term consequences after stroke. The survey comprises
      a set of self-evaluated questionnaires and was sent to 457 persons, of whom 281
      responded (61.5%). From the survey, items regarding transportation and mobility
      were selected and analyzed. Results A high level of mobility function was
      reported with regard to outdoor mobility and different modes of transport.
      However, one-fifth still reported problems with outdoor mobility and mode of
      transport. Some perceived barriers were reported, predominantly mobility aspects
      such as transfer to/from, and getting on/off specific transportation mode/s. The
      respondents reported some communication problems and cognitive impairments, but
      these were not reported as prominent barriers when using public transport. A
      total of 67% were active drivers and were more often men (p = 0.002), younger (p
      <= 0.001), and were less dependent at discharge from the acute hospital (p <=
      0.001). Conclusions Five years post-stroke, mobility problems were the dominant
      barrier reported when using transport modes. Individualized transport training is
      needed during rehabilitation to increase possibility to participate.
      Infrastructure and transportation planning should focus on older, women, and
      people with impairments to be able to facilitate the use of public transport and
      mobility.

PMID- 29334332
TI  - Quantifying lower extremity and trunk function for dressing in stroke patients: a
      retrospective observational study.
AB  - Background Dressing performance relates strongly with balance function, and it is
      mainly influenced by the motor functions of the affected and unaffected lower
      extremity and trunk function in stroke patients. For the remedial approach to be
      effective, ascertaining the degree of function needed in the affected and
      unaffected lower extremities and trunk to achieve balance function requisite for
      dressing is necessary. Objectives This study aimed to elucidate standards of
      lower extremity and trunk function necessary for stroke patients to gain balance
      requisite for dressing. Methods The study included 105 first-time stroke
      patients, who were classified by Berg Balance Score >=44 or not and >=32 or not
      which are previously reported standard indicators for independent and supervision
      level in dressing. Receiver operating characteristic curves were determined for
      the stroke impairment assessment item of sensory and motor function of affected
      lower extremity, abdominal muscle strength, and knee extension muscle strength.
      Results Area under the curve was >=0.7 for all variables. In BBS 44-point
      analyses, the calculated cut-off values were 4 points for SIAS hip flexion, 4
      points for SIAS knee extension, 2 points for SIAS foot pat on the affected side,
      3 points for SIAS tactile and position sensation of the affected lower extremity,
      3 points for SIAS abdominal muscle strength, and 3 points for SIAS knee extension
      muscle strength on the unaffected side. Conclusions These cut-off values can be
      used as targets for motor functions, when using the remedial approach for
      achieving dressing independence.

PMID- 29334333
TI  - Are people at high risk for diabetes visiting health facility for confirmation of
      diagnosis? A population-based study from rural India.
AB  - BACKGROUND: India is witnessing a rising burden of type 2 diabetes mellitus.
      India's National Programme for Prevention and Control of Diabetes, Cancer,
      Cardiovascular diseases and Stroke recommends population-based screening and
      referral to primary health centre for diagnosis confirmation and treatment
      initiation. However, little is known about uptake of confirmatory tests among
      screen positives. OBJECTIVE: To estimate the uptake of confirmatory tests and
      identify the reasons for not undergoing confirmation by those at high risk for
      developing diabetes. METHODS: We analysed data collected under project UDAY, a
      comprehensive diabetes and hypertension prevention and management programme,
      being implemented in rural Andhra Pradesh, India. Under UDAY, population-based
      screening for diabetes was carried out by project health workers using a diabetes
      risk score and capillary blood glucose test. Participants at high risk for
      diabetes were asked to undergo confirmatory tests. On follow-up visit, health
      workers assessed if the participant had undergone confirmation and ask for
      reasons if not so. RESULTS: Of the 35,475 eligible adults screened between April
      2015 and August 2016, 10,960 (31%) were determined to be at high risk. Among
      those at high risk, 9670 (88%) were followed up, and of those, only 616 (6%)
      underwent confirmation. Of those who underwent confirmation, 'lack of symptoms of
      diabetes warranting visit to health facility' (52%) and 'being at high risk was
      not necessary enough to visit' (41%) were the most commonly reported reasons for
      non-confirmation. Inconvenient facility time (4.4%), no nearby facility (3.2%),
      un-affordability (2.2%) and long waiting time (1.6%) were the common health
      system-related factors that affected the uptake of the confirmatory test.
      CONCLUSION: Confirmation of diabetes was abysmally low in the study population.
      Low uptake of the confirmatory test might be due to low 'risk perception'. The
      uptake can be increased by improving the population risk perception through
      individual and/or community-focused risk communication interventions.

PMID- 29334334
TI  - Mortality after endovascular treatment of infrarenal abdominal aortic aneurysms -
      the newer the better?
AB  - Although endovascular repair of infrarenal abdominal aortic aneurysms (EVAR)
      presents a delicate alternative treatment for abdominal aortic aneurysms (AAA)
      with lower perioperative mortality, its long-term efficacy remains a matter of
      concern. The purpose of this study was to evaluate the currently reported
      mortality evidence after EVAR and to examine the possible effect of aneurysm
      status and the study period on mortality rates. The PubMed and Cochrane
      bibliographical databases were thoroughly searched for studies reporting on more
      than 1 000 patients with non-ruptured or ruptured infrarenal AAA, treated with
      EVAR from August 1991 to September 2016. A total of 10 910 titles/abstracts were
      retrieved and 121 studies were deemed relevant. Twenty-six studies met the
      inclusion criteria and reported on 354 500 patients with a mean age of 74.6
      years. Almost all of the studies referred to elective EVAR and the mean aneurysm
      size was 5.58 cm. The most common early complication for elective EVAR was
      perioperative bleeding (1.9 %), whereas hospital-acquired pneumonia was a major
      concern in urgent EVAR (28.5 %). Conversion rate to open surgery was 1.2 %. The
      30-day all-cause mortality rate was 4.84 % (1.7 % for non- ruptured aneurysms,
      33.8 % for ruptured aneurysms).The overall all-cause late mortality in a mean
      follow-up period of 23.8 months was 19.1 %. The aneurysm-related late mortality
      rate was 3.4 %. With respect to the time period of patient enrollment, studies
      reporting on patients recruited before 2006 were found to face more secondary
      complications and higher late mortality rates than patients enrolled after
      2005.The endovascular treatment of large and anatomically suitable infrarenal AAA
      in selected patients remains a safe alternative to open repair. Our findings
      demonstrate that newer studies show better long-term outcomes than the older
      ones, proposing a possible improvement of EVAR techniques and perioperative care
      and providing encouraging evidence for a wider application of EVAR.

PMID- 29334335
TI  - Simultaneous formation of polycyclic aromatic hydrocarbons (PAHs) and
      heterocyclic aromatic amines (HCAs) in gas-grilled beef satay at different
      temperatures.
AB  - This study investigated the simultaneous formation of polycyclic aromatic
      hydrocarbons (PAHs) and heterocyclic aromatic amines (HCAs) in gas-grilled beef
      satay at different temperatures (150, 200, 250, 300, and 350 degrees C). Solid
      phase extraction (SPE) was used for sample clean-up. Fifteen PAHs were determined
      using high performance liquid chromatography with fluorescence detection (HPLC
      FLD) and nine HCAs were quantified using liquid chromatography tandem-mass
      spectrometry (LC-MS/MS) with a gradient programme. The lowest significantly
      concentrations of PAHs and HCAs were generated at 150 degrees C; the formation of
      PAHs and HCAs simultaneously increased with temperatures. Benzo[a]pyrene was
      detected in all samples and increased markedly at 300 and 350 degrees C. The sums
      of 4 PAHs (PAH4) in marinated beef satay at 300 and 350 degrees C exceeded the
      maximum level in Commission Regulation (EU) 2015/1125. Significant reductions of
      polar and non-polar HCAs (except PhIP) were found in marinated beef satay across
      all temperatures. Overall, PAHs and HCAs showed opposite trends of formation in
      beef satay with marination.

PMID- 29334336
TI  - Engineering mechanical microenvironment of macrophage and its biomedical
      applications.
AB  - Macrophages are the most plastic cells in the hematopoietic system and can be
      widely found in almost all tissues. Recently studies have shown that mechanical
      cues (e.g., matrix stiffness and stress/strain) can significantly affect
      macrophage behaviors. Although existing reviews on the physical and mechanical
      cues that regulate the macrophage's phenotype are available, engineering
      mechanical microenvironment of macrophages in vitro as well as a comprehensive
      overview and prospects for their biomedical applications (e.g., tissue
      engineering and immunotherapy) has yet to be summarized. Thus, this review
      provides an overview on the existing methods for engineering mechanical
      microenvironment of macrophages in vitro and then a section on their biomedical
      applications and further perspectives are presented.

PMID- 29334337
TI  - Durable responses in refractory autoimmune hemolytic anemia with alemtuzumab.
AB  - Autoimmune hemolytic anemia occurs due to an interaction of IgG antibodies with
      protein antigens expressed on red blood corpuscles. Glucocorticoids are the
      mainstay of treatment for autoimmune hemolytic anemia. For patients not
      responding to initial therapy, other agents such as rituximab, immunosuppressive
      therapy, or splenectomy are considered. When refractory to these treatment
      options, alemtuzumab is an alternative agent. However, long-term outcomes of
      patients supporting its use are lacking. We present three patients with
      refractory autoimmune hemolytic anemia treated with alemtuzumab.

PMID- 29334338
TI  - At-home genital nerve stimulation for individuals with SCI and neurogenic
      detrusor overactivity: A pilot feasibility study.
AB  - OBJECTIVE: Neurogenic bladder dysfunction, including neurogenic detrusor
      overactivity (NDO) is one of the most clinically significant problems for persons
      with spinal cord injury (SCI), affecting health and quality of life. Genital
      nerve stimulation (GNS) can acutely inhibit NDO-related reflex bladder
      contractions and increase bladder capacity. However, it is unknown if GNS can
      improve urinary continence or help meet individuals' bladder management goals
      during sustained use, which is required for GNS to be clinically effective.
      DESIGN: Subjects maintained voiding diaries during a one-month control period
      without stimulation, one month with at-home GNS, and one month after GNS.
      Urodynamics and quality of life assessments were conducted after each treatment
      period, and a satisfaction survey was taken at study completion. SETTING: Subject
      screening and clinical procedures were conducted at the Louis Stokes Cleveland VA
      Medical Center. Stimulation use and voiding diary entries were conducted in
      subjects' homes. PARTICIPANTS: Subjects included five men with SCI and NDO.
      INTERVENTIONS: This study tested one month of at-home portable non-invasive GNS.
      OUTCOME MEASURES: The primary outcome measure was leakage events per day.
      Secondary outcome measures included self-reported subject satisfaction, bladder
      capacity, and stimulator use frequency. RESULTS: GNS reduced the number of
      leakage events from 1.0 +/- 0.5 to 0.1 +/- 0.4 leaks per day in the four subjects
      who reported incontinence data. All study participants were satisfied that GNS
      met their bladder goals; wanted to continue using GNS; and would recommend it to
      others. CONCLUSIONS: Short term at-home GNS reduced urinary incontinence and
      helped subjects meet their bladder management goals. These data inform the design
      of a long-term clinical trial testing of GNS as an approach to reduce NDO.

PMID- 29334339
TI  - Impact of spasticity on transfers and activities of daily living in individuals
      with spinal cord injury.
AB  - CONTEXT/OBJECTIVE: For persons with spinal cord injury, spasticity commonly
      interferes with activities of daily living such as transfers. Electromyography
      can be used to objectively measure muscle spasms during transfers, but how
      electromyographic measures relate to the impact spasticity has on life, or to
      clinically-rated spasticity, is unclear. We aimed to characterize relationships
      among spasm duration and magnitude, impact of spasticity on daily life, and a
      clinical measure of extensor spasticity, as well as to determine reliability of
      the electromyographic measures. DESIGN: Participants (N=19) underwent
      electromyographic measurements of involuntary muscle activity (spasm duration and
      magnitude) evoked in quadriceps muscles during transfers on two days. Impact of
      spasticity on daily life was measured with the Spinal Cord Injury Spasticity
      Evaluation Tool. Clinically-rated spasticity severity was measured with the
      Spinal Cord Assessment Tool for Spastic reflexes. RESULTS: No significant
      associations were found between impact of spasticity and spasm duration, spasm
      magnitude, or clinical extensor spasticity score. Absolute and normalized spasm
      duration were positively associated with clinical extensor spasticity score
      (rho=0.510-0.667, P < 0.05). Spasm measures during transfers had good to
      excellent day-to-day reliability (rho=0.656-0.846, P < 0.05). CONCLUSIONS:
      Electromyographic and clinical measures of involuntary activity in the lower
      extremity do not significantly relate to perceived impact of spasticity on daily
      life. However, quadriceps spasm duration during transfers is related to
      clinically-rated extensor spasticity. Electromyography is a reliable method of
      quantifying quadriceps spasms during transfers. Future investigations should
      identify factors that influence the impact of spasticity on life, which may help
      direct treatment strategies to reduce problematic impact.

PMID- 29334340
TI  - Identification of anti-filarial leads against aspartate semialdehyde
      dehydrogenase of Wolbachia endosymbiont of Brugia malayi: combined molecular
      docking and molecular dynamics approaches.
AB  - Lymphatic filariasis is a debilitating vector borne parasitic disease that
      infects human lymphatic system by nematode Brugia malayi. Currently available
      anti-filarial drugs are effective only on the larval stages of parasite. So far,
      no effective drugs are available for humans to treat filarial infections. In this
      regard, aspartate semialdehyde dehydrogenase (ASDase) in lysine biosynthetic
      pathway from Wolbachia endosymbiont Brugia malayi represents an attractive
      therapeutic target for the development of novel anti-filarial agents. In this
      present study, molecular modeling combined with molecular dynamics simulations
      and structure-based virtual screening were performed to identify potent lead
      molecules against ASDase. Based on Glide score, toxicity profile, binding
      affinity and mode of interactions with the ASDase, five potent lead molecules
      were selected. The molecular docking and dynamics results revealed that the amino
      acid residues Arg103, Asn133, Cys134, Gln161, Ser164, Lys218, Arg239, His246, and
      Asn321 plays a crucial role in effective binding of Top leads into the active
      site of ASDase. The stability of the ASDase-lead complexes was confirmed by
      running the 30 ns molecular dynamics simulations. The pharmacokinetic properties
      of the identified lead molecules are in the acceptable range. Furthermore,
      density functional theory and binding free energy calculations were performed to
      rank the lead molecules. Thus, the identified lead molecules can be used for the
      development of anti-filarial agents to combat the pathogenecity of Brugia malayi.

PMID- 29334341
TI  - Thyroid-Related Research in Japan A Spotlight on Recent Important Contributions.

PMID- 29334343
TI  - Breast-Milk Iodine Concentrations and Iodine Levels of Infants According to the
      Iodine Status of the Country of Residence: A Systematic Review and Meta-Analysis.
AB  - BACKGROUND: Iodine, an essential micronutrient, plays a critical role in normal
      growth and development, especially during the first two years of life. This
      systematic review and meta-analysis is among the first to evaluate breast-milk
      iodine concentrations and infant iodine status in countries characterized by
      iodine sufficiency or deficiency. METHODS: PubMed, Web of Science, Cochrane
      Library, Google Scholar, and other relevant databases, as well as reference lists
      of previous reviews, were searched for relevant studies published between 1986
      and 2016. Mean or median breast-milk and infant urinary iodine concentrations,
      along with other relevant data, were extracted from eligible studies. Each study
      was assessed for quality and risk of bias. RESULTS: Of the 496 identified
      studies, 57 met the criteria for inclusion in the meta-analysis. The mean
      (confidence interval [CI]) iodine concentrations in maternal colostrum were 152.0
      MUg/L [CI 106.2-198.7 MUg/L] and 57.8 MUg/L [CI 41.4-74.1 MUg/L] in iodine
      sufficient and -deficient countries, respectively, indicating a significant
      difference between the two iodine statuses. By contrast, the corresponding values
      in mature milk did not differ significantly between mothers in iodine-sufficient
      and -deficient countries (71.5 MUg/L [CI 51.0-92.0 MUg/L] and 28.0 MUg/L [CI 
      13.8 to 69.9 MUg/L], respectively]. The weighted urinary iodine levels [CIs] of
      breast-fed infants in iodine-sufficient countries were significantly higher than
      those in iodine-deficient countries (164.5 MUg/L [CI 116.4-212.7 MUg/L] vs. 70.4
      MUg/L [CI 46.2-94.6 MUg/L]). Similarly, a significant difference was observed in
      the pooled estimates of urinary iodine levels [CIs] among formula-fed infants in
      iodine-sufficient versus iodine-deficient countries (310.3 MUg/L [CI 287.4-342.1
      MUg/L] vs. 38.3 MUg/L [CI 23.4-53.2 MUg/L]). CONCLUSION: The meta-analysis
      reveals that in iodine-sufficient countries, the mean iodine concentrations in
      colostrum and mature breast milk corresponded to iodine sufficiency among
      infants. The results are thus compatible with the international recommendation
      that lactating women and infants younger than two years of age who reside in
      iodine-sufficient countries do not require iodine supplementation.

PMID- 29334345
TI  - Arm crank ergometry improves cardiovascular disease risk factors and community
      mobility independent of body composition in high motor complete spinal cord
      injury.
AB  - OBJECTIVE: Evaluate the effect of aerobic exercise using arm crank ergometry
      (ACE) in high motor complete (ISNCSCI A/B) spinal cord injury (SCI) as primarily
      related to cardiovascular disease (CVD) risk factors and functional mobility and
      secondarily to body composition and metabolic profiles. DESIGN: Longitudinal
      interventional study at an academic medical center. METHODS: Ten previously
      untrained participants (M8/F2, Age 36.7 y +/- 10.1, BMI 24.5 +/- 6.0) with high
      motor complete SCI (C7-T5) underwent ACE exercise training 30 minutes/day * 3
      days/week for 10 weeks at 70% VO2Peak. OUTCOME MEASURES: Primary outcome measures
      were pre- and post-intervention changes in markers of cardiovascular fitness
      (graded exercise testing (GXT): VO2, VO2Peak, respiratory quotient [RQ], GXT
      time, peak power, and energy expenditure [EE]) and community mobility (time to
      traverse a 100ft-5 degrees  ramp, and 12-minute WC propulsion test). Secondary
      outcome measures were changes in body composition and metabolic profiles (fasting
      and area under the curve for glucose and insulin, homeostasis model assessment
      [HOMA] for %beta-cell activity [%beta], %insulin sensitivity [%S], and insulin
      resistance [IR], and Matsuda Index [ISIMatsuda]). RESULTS: Resting VO2, relative
      VO2Peak, absolute VO2Peak, peak power, RQ, 12-minute WC propulsion, fasting
      insulin, fasting G:I ratio, HOMA-%S, and HOMA-IR all significantly improved
      following intervention (P < 0.05). There were no changes in body composition
      (P>0.05). CONCLUSIONS: Ten weeks of ACE at 70% VO2Peak in high motor complete SCI
      improves aerobic capacity, community mobility, and metabolic profiles independent
      of changes in body composition.

PMID- 29334346
TI  - In this issue: Prerequisites for precision medicine are genomics, computerised
      medical record systems, and big data analytics.

PMID- 29334344
TI  - Content validity and satisfaction with a caregiver-integrated web-based
      rehabilitation intervention for persons with stroke.
AB  - Background Family members provide valuable contributions during rehabilitation
      after stroke, but frequently report higher incidences of burden, depression, and
      social isolation during caregiving. Thus, effective interventions to reduce
      stroke impact on the family are needed. Objectives To evaluate the content
      validity and satisfaction of a caregiver-focused web-based intervention designed
      to improve stroke survivor physical function while reducing caregiver negative
      outcomes. Methods Caregivers of individuals with stroke (N = 6) and expert
      rehabilitation researchers (N = 4) were presented with a novel, web-based
      intervention (CARE-CITE) designed to foster problem-solving and skill-building
      while facilitating caregiver involvement during constraint-induced movement
      therapy. Caregivers rated CARE-CITE for usefulness, ease of use, acceptability,
      and time to complete. Rehabilitation experts evaluated content for accuracy,
      feasibility, acceptability, problem relevance and ease of use. Ratings were
      assessed using a five-point Likert-type response scales (1 = strongly disagree to
      5 = strongly agree). Results On average, all caregivers agreed or strongly agreed
      that the modules were useful (4.42), easy to use (4.60), and acceptable (4.41).
      Mean total satisfaction score was 4.45, and average review time was 15 min per
      module. Expert reviewers agreed or strongly agreed that each module was accurate
      (4.95), feasible (4.8), easy to use (4.86), acceptable (4.96), and had
      appropriate problem relevance (4.65). Conclusions The CARE-CITE intervention may
      be a viable program for caregivers of patients with stroke. Currently a pilot
      study is underway to evaluate the impact of the intervention on caregiver mental
      health, family conflict around stroke recovery and stroke survivor upper
      extremity function.

PMID- 29334347
TI  - Methods to Describe Referral Patterns in a Canadian Primary Care Electronic
      Medical Record Database: Modelling Multilevel Count Data.
AB  - BACKGROUND:   A referral from a family physician (FP) to a specialist is an
      inflection point in the patient journey, with potential implications for clinical
      outcomes and health policy. Primary care electronic medical record (EMR)
      databases offer opportunities to examine referral patterns. Until recently,
      software techniques were not available to model these kinds of multi-level count
      data. OBJECTIVE:  To establish methodology for determining referral rates from
      FPs to medical specialists using the Canadian Primary Care Sentinel Surveillance
      Network (CPCSSN) EMR database. METHOD: Retrospective cohort study, mixed effects
      and multi-level negative binomial regression modelling with 87,258 eligible
      patients between 2007 and 2012. Mean referrals compared by patient sex, age,
      chronic conditions, FP visits, and urban/rural practice location.  Proportion of
      variance in referral rates attributable to the patient and practice levels.
      RESULTS:  On average, males had 0.26, and females 0.31 referrals in a 12-month
      period.  Referrals were significantly higher for females, increased with age, FP
      visits, and number of chronic conditions (p<.0001). Overall, 14% of the variance
      in referrals could be attributed to the practice level, and 86% to patient level
      characteristics. CONCLUSIONS:  Both patient and practice characteristics
      influenced referral patterns. The methodologic insights gained from this study
      have relevance to future studies on many research questions that utilize count
      data, both within primary care and broader health services research. The utility
      of the CPCSSN database will continue to increase in tandem with data quality
      improvements, providing a valuable resource to study Canadian referral patterns
      over time.

PMID- 29334348
TI  - Assessing the readiness of precision medicine interoperabilty: An exploratory
      study of the National Institutes of Health genetic testing registry.
AB  - BACKGROUND:   Precision medicine involves three major innovations currently
      taking place in healthcare:  electronic health records, genomics, and big data. 
      A major challenge for healthcare providers, however, is understanding the
      readiness for practical application of initiatives like precision medicine.
      OBJECTIVE:   To better understand the current state and challenges of precision
      medicine interoperability using a national genetic testing registry as a starting
      point, placed in the context of established interoperability formats. METHODS:  
      We performed an exploratory analysis of the National Institutes of Health Genetic
      Testing Registry.  Relevant standards included Health Level Seven International
      Version 3 Implementation Guide for Family History, the Human Genome Organization
      Gene Nomenclature Committee (HGNC) database, and Systematized Nomenclature of
      Medicine - Clinical Terms (SNOMED CT).  We analyzed the distribution of genetic
      testing laboratories, genetic test characteristics, and standardized
      genome/clinical code mappings, stratified by laboratory setting. RESULTS: There
      were a total of 25472 genetic tests from 240 laboratories testing for
      approximately 3632 distinct genes.  Most tests focused on diagnosis, mutation
      confirmation, and/or risk assessment of germline mutations that could be passed
      to offspring.  Genes were successfully mapped to all HGNC identifiers, but less
      than half of tests mapped to SNOMED CT codes, highlighting significant gaps when
      linking genetic tests to standardized clinical codes that explain the medical
      motivations behind test ordering.  Conclusion:  While precision medicine could
      potentially transform healthcare, successful practical and clinical application
      will first require the comprehensive and responsible adoption of interoperable
      standards, terminologies, and formats across all aspects of the precision
      medicine pipeline.

PMID- 29334349
TI  - Research Outputs of England's Hospital Episode Statistics (HES) Database:
      Bibliometric Analysis.
AB  - BACKGROUND: Hospital administrative data, such as those provided by the Hospital
      Episode Statistics (HES) database in England, are increasingly being used for
      research and quality improvement. To date, no study has tried to quantify and
      examine trends in the use of HES for research purposes. OBJECTIVE: To examine
      trends in the use of HES data for research. METHODS: Publications generated from
      the use of HES data were extracted from PubMed and analysed. Publications from
      1996 to 2014 were then examined further in the Science Citation Index (SCI) of
      the Thompson Scientific Institute for Science Information (Web of Science) for
      details of research specialty area. RESULTS: 520 studies, categorised into 44
      specialty areas, were extracted from PubMed. The review showed an increase in
      publications over the 18-year period with an average of 27 publications per year,
      however with the majority of output observed in the latter part of the study
      period. The highest number of publications was in the Health Statistics specialty
      area. CONCLUSION: The use of HES data for research is becoming more common.
      Increase in publications over time shows that researchers are beginning to take
      advantage of the potential of HES data. Although HES is a valuable database,
      concerns exist over the accuracy and completeness of the data entered. Clinicians
      need to be more engaged with HES for the full potential of this database to be
      harnessed.

PMID- 29334350
TI  - Bespoke automation of medical workforce rostering using Google's free cloud
      applications.
AB  - BACKGROUND: Providing safe and consistent care requires optimal deployment of
      medical staff. Ensuring this happens is a significant administrative burden due
      to complex working patterns. OBJECTIVE: To describe a pilot feasibility study of
      the automation of medical duty rostering in a busy tertiary Ophthalmology
      department. METHODS: A cloud based web application was created using Google's
      free cloud services. Users access the system via a website which hosts live
      rosters, and use electronic forms to submit requests which are automatically
      handled by Google App Scripts. RESULTS: Over a 2-year period (8/2014-6/2016), the
      system processed 563 leave requests and 300 on call swaps automatically. 3,300
      emails and 1,000 forms were automatically generated. User satisfaction was 100%
      (n=24). DISCUSSION: Many time consuming aspects of roster management were
      automated with significant time savings to all parties, allowing increased
      clinical time for doctors involved in administration. Planning for safe staffing
      levels was supported.

PMID- 29334351
TI  - Integrating third-party telehealth records with the general practice electronic
      medical record system: a solution.
AB  - BACKGROUND: The implementation of telemonitoring at scale has been less
      successful than anticipated, often hindered by clinicians' perceived increase in
      workload. One important factor has been the lack of integration of patient
      generated data (PGD) with the electronic medical record (EMR). Clinicians have
      had problems accessing PGD on telehealth systems especially in patient
      consultations in primary care. OBJECTIVE: To design a method to produce a report
      of PGD that is available to clinicians through their routine EMR system. METHOD:
      We modelled a system with a use case approach using Unified Modelling Language to
      enable us to design a method of producing the required report. Anonymised PGD are
      downloaded from a third-party telehealth system to National Health Service (NHS)
      systems and linked to the patient record available in the hospital recording
      system using the patient NHS ID through an interface accessed by healthcare
      professionals. The telehealth data are then processed into a report using the
      patient record. This report summarises the readings in graphical and tabular form
      with an average calculated and with a recommended follow-up suggested if
      required. The report is then disseminated to general practitioner practices
      through routine document distribution pathways. RESULTS: This addition to the
      telehealth system is viewed positively by clinicians. It has helped to greatly
      increase the number of general practices using telemonitoring to manage blood
      pressure in NHS Lothian.

PMID- 29334352
TI  - The Multimorbidity Cluster Analysis Tool: Identifying Combinations and
      Permutations of Multiple Chronic Diseases Using a Record-Level Computational
      Analysis.
AB  - INTRODUCTION: Multimorbidity, or the co-occurrence of multiple chronic health
      conditions within an individual, is an increasingly dominant presence and burden
      in modern health care systems.  To fully capture its complexity, further research
      is needed to uncover the patterns and consequences of these co-occurring health
      states.  As such, the Multimorbidity Cluster Analysis Tool and the accompanying
      Multimorbidity Cluster Analysis Toolkit have been created to allow researchers to
      identify distinct clusters that exist within a sample of participants or patients
      living with multimorbidity. Development: The Tool and Toolkit were developed at
      Western University in London, Ontario, Canada.  This open-access computational
      program (JAVA code and executable file) was developed and tested to support an
      analysis of thousands of individual records and up to 100 disease diagnoses or
      categories. APPLICATION: The computational program can be adapted to the
      methodological elements of a research project, including type of data, type of
      chronic disease reporting, measurement of multimorbidity, sample size and
      research setting.  The computational program will identify all existing, and
      mutually exclusive, combinations and permutations within the dataset.  An
      application of this computational program is provided as an example, in which
      more than 75,000 individual records and 20 chronic disease categories resulted in
      the detection of 10,411 unique combinations and 24,647 unique permutations among
      female and male patients. DISCUSSION: The Tool and Toolkit are now available for
      use by researchers interested in exploring the complexities of multimorbidity. 
      Its careful use, and the comparison between results, will be valuable additions
      to the nuanced understanding of multimorbidity.

PMID- 29334353
TI  - Genesis of a UK Faculty of Clinical Informatics at a time of anticipation for
      some, and ruby, golden and diamond celebrations for others.
AB  - This Editorial marks the launch of the UK Faculty of Clinical Informatics (FCI)
      at the time when non-clinically qualified informaticians are anticipating the
      lauch of  the Federation of Informatics Professionals in Health and Care (Fed
      IP).

PMID- 29334354
TI  - Real World Evidence to an eHealth tool: The 2017 top ten papers from Journal of
      Innovation in Health Informatics.
AB  - We report the top ten papers published by the Journal ofInnovation in Health
      Informatics in 2017.

PMID- 29334355
TI  - Retraction: Genetic characterization and assessment of demographic bottleneck in
      Caspian horse population.
AB  - [This delete the article DOI: 10.14715/cmb/2017.63.11.16.].

PMID- 29334358
TI  - Fingerprints of a position-dependent Fermi velocity on scanning tunnelling
      spectra of strained graphene.
AB  - Nonuniform strain in graphene induces a position dependence of the Fermi
      velocity, as recently demonstrated by scanning tunnelling spectroscopy
      experiments. In this work, we study the effects of a position-dependent Fermi
      velocity on the local density of states (LDOS) of strained graphene, with and
      without the presence of a uniform magnetic field. The variation of LDOS obtained
      from tight-binding calculations is successfully explained by analytical
      expressions derived within the Dirac approach. These expressions also rectify a
      rough Fermi velocity substitution used in the literature that neglects the strain
      induced anisotropy. The reported analytical results could be useful for
      understanding the nonuniform strain effects on scanning tunnelling spectra of
      graphene, as well as when it is exposed to an external magnetic field.

PMID- 29334356
TI  - p53 orchestrates DNA replication restart homeostasis by suppressing mutagenic
      RAD52 and POLtheta pathways.
AB  - Classically, p53 tumor suppressor acts in transcription, apoptosis, and cell
      cycle arrest. Yet, replication-mediated genomic instability is integral to
      oncogenesis, and p53 mutations promote tumor progression and drug-resistance. By
      delineating human and murine separation-of-function p53 alleles, we find that p53
      null and gain-of-function (GOF) mutations exhibit defects in restart of stalled
      or damaged DNA replication forks that drive genomic instability, which
      isgenetically separable from transcription activation. By assaying protein-DNA
      fork interactions in single cells, we unveil a p53-MLL3-enabled recruitment of
      MRE11 DNA replication restart nuclease. Importantly, p53 defects or depletion
      unexpectedly allow mutagenic RAD52 and POLtheta pathways to hijack stalled forks,
      which we find reflected in p53 defective breast-cancer patient COSMIC mutational
      signatures. These data uncover p53 as a keystone regulator of replication
      homeostasis within a DNA restart network. Mechanistically, this has important
      implications for development of resistance in cancer therapy. Combined, these
      results define an unexpected role for p53-mediated suppression of replication
      genome instability.

PMID- 29334359
TI  - Electronic and optical properties of spinel zinc ferrite: ab initio hybrid
      functional calculations.
AB  - Spinel ferrites in general show a rich interplay of structural, electronic, and
      magnetic properties. Here, we particularly focus on zinc ferrite (ZFO), which has
      been observed experimentally to crystallise in the cubic normal spinel structure.
      However, its magnetic ground state is still under dispute. In addition, some
      unusual magnetic properties in ZFO thin films or nanostructures have been
      explained by a possible partial cation inversion and a different magnetic
      interaction between the two cation sublattices of the spinel structure compared
      to the crystalline bulk material. Here, density functional theory has been
      applied to investigate the influence of different inversion degrees and magnetic
      couplings among the cation sublattices on the structural, electronic, magnetic,
      and optical properties. Effects of exchange and correlation have been modelled
      using the generalised gradient approximation (GGA) together with the Hubbard '+U'
      parameter, and the more elaborate hybrid functional PBE0. While the GGA+U
      calculations yield an antiferromagnetically coupled normal spinel structure as
      the ground state, in the PBE0 calculations the ferromagnetically coupled normal
      spinel is energetically slightly favoured, and the hybrid functional calculations
      perform much better with respect to structural, electronic and optical
      properties.

PMID- 29334357
TI  - Differential requirements of androgen receptor in luminal progenitors during
      prostate regeneration and tumor initiation.
AB  - Master regulatory genes of tissue specification play key roles in stem/progenitor
      cells and are often important in cancer. In the prostate, androgen receptor (AR)
      is a master regulator essential for development and tumorigenesis, but its
      specific functions in prostate stem/progenitor cells have not been elucidated. We
      have investigated AR function in CARNs (CAstration-Resistant Nkx3.1-expressing
      cells), a luminal stem/progenitor cell that functions in prostate regeneration.
      Using genetically--engineered mouse models and novel prostate epithelial cell
      lines, we find that progenitor properties of CARNs are largely unaffected by AR
      deletion, apart from decreased proliferation in vivo. Furthermore, AR loss
      suppresses tumor formation after deletion of the Pten tumor suppressor in CARNs;
      however, combined Pten deletion and activation of oncogenic Kras in AR-deleted
      CARNs result in tumors with focal neuroendocrine differentiation. Our findings
      show that AR modulates specific progenitor properties of CARNs, including their
      ability to serve as a cell of origin for prostate cancer.

PMID- 29334360
TI  - Self-consistent description of local density dynamics in simple liquids. The case
      of molten lithium.
AB  - The dynamic structure factor is the quantity, which can be measured by means of
      Brillouin light-scattering as well as by means of inelastic scattering of
      neutrons and x-rays. The spectral (or frequency) moments of the dynamic structure
      factor define directly the sum rules of the scattering law. The theoretical
      scheme formulated in this study allows one to describe the dynamics of local
      density fluctuations in simple liquids and to obtain the expression of the
      dynamic structure factor in terms of the spectral moments. The theory satisfies
      all the sum rules, and the obtained expression for the dynamic structure factor
      yields correct extrapolations into the hydrodynamic limit as well as into the
      free-particle dynamics limit. We discuss correspondence of this theory with the
      generalized hydrodynamics and with the viscoelastic models, which are commonly
      used to analyze the data of inelastic neutron and x-ray scattering in liquids. In
      particular, we reveal that the postulated condition of the viscoelastic model for
      the memory function can be directly obtained within the presented theory. The
      dynamic structure factor of liquid lithium is computed on the basis of the
      presented theory, and various features of the scattering spectra are evaluated.
      It is found that the theoretical results are in agreement with inelastic x-ray
      scattering data.

PMID- 29334361
TI  - Engineering the spin polarization of one-dimensional electrons.
AB  - We present results of magneto-focusing on the controlled monitoring of spin
      polarization within a one-dimensional (1D) channel, and its subsequent effect on
      modulating the spin-orbit interaction (SOI) in a 2D GaAs electron gas. We
      demonstrate that electrons within a 1D channel can be partially spin polarized as
      the effective length of the 1D channel is varied in agreement with the
      theoretical prediction. Such polarized 1D electrons when injected into a 2D
      region result in a split in the odd-focusing peaks, whereas the even peaks remain
      unaffected (single peak). On the other hand, the unpolarized electrons do not
      affect the focusing spectrum and the odd and even peaks remain as single peaks,
      respectively. The split in odd-focusing peaks is evidence of direct measurement
      of spin polarization within a 1D channel, where each sub-peak represents the
      population of a particular spin state. Confirmation of the spin splitting is
      determined by a selective modulation of the focusing peaks due to the Zeeman
      energy in the presence of an in-plane magnetic field. We suggest that the SOI in
      the 2D regime is enhanced by a stream of polarized 1D electrons. The spatial
      control of spin states of injected 1D electrons and the possibility of tuning the
      SOI may open up a new regime of spin-engineering with application in future
      quantum information schemes.

PMID- 29334362
TI  - Investigation of resistance switching in SiO x RRAM cells using a 3D multi-scale
      kinetic Monte Carlo simulator.
AB  - We employ an advanced three-dimensional (3D) electro-thermal simulator to explore
      the physics and potential of oxide-based resistive random-access memory (RRAM)
      cells. The physical simulation model has been developed recently, and couples a
      kinetic Monte Carlo study of electron and ionic transport to the self-heating
      phenomenon while accounting carefully for the physics of vacancy generation and
      recombination, and trapping mechanisms. The simulation framework successfully
      captures resistance switching, including the electroforming, set and reset
      processes, by modeling the dynamics of conductive filaments in the 3D space. This
      work focuses on the promising yet less studied RRAM structures based on silicon
      rich silica (SiO x ) RRAMs. We explain the intrinsic nature of resistance
      switching of the SiO x layer, analyze the effect of self-heating on device
      performance, highlight the role of the initial vacancy distributions acting as
      precursors for switching, and also stress the importance of using 3D physics
      based models to capture accurately the switching processes. The simulation work
      is backed by experimental studies. The simulator is useful for improving our
      understanding of the little-known physics of SiO x resistive memory devices, as
      well as other oxide-based RRAM systems (e.g. transition metal oxide RRAMs),
      offering design and optimization capabilities with regard to the reliability and
      variability of memory cells.

PMID- 29334363
TI  - Macrophage membrane-coated iron oxide nanoparticles for enhanced photothermal
      tumor therapy.
AB  - Nanotechnology possesses the potential to revolutionize the diagnosis and
      treatment of tumors. The ideal nanoparticles used for in vivo cancer therapy
      should have long blood circulation times and active cancer targeting.
      Additionally, they should be harmless and invisible to the immune system. Here,
      we developed a biomimetic nanoplatform with the above properties for cancer
      therapy. Macrophage membranes were reconstructed into vesicles and then coated
      onto magnetic iron oxide nanoparticles (Fe3O4 NPs). Inherited from the Fe3O4 core
      and the macrophage membrane shell, the resulting Fe3O4@MM NPs exhibited good
      biocompatibility, immune evasion, cancer targeting and light-to-heat conversion
      capabilities. Due to the favorable in vitro and in vivo properties, biomimetic
      Fe3O4@MM NPs were further used for highly effective photothermal therapy of
      breast cancer in nude mice. Surface modification of synthetic nanomaterials with
      biomimetic cell membranes exemplifies a novel strategy for designing an ideal
      nanoplatform for translational medicine.

PMID- 29334364
TI  - Compactness of viral genomes: effect of disperse and localized random mutations.
AB  - Genomes of single-stranded RNA viruses have evolved to optimize several
      concurrent properties. One of them is the architecture of their genomic folds,
      which must not only feature precise structural elements at specific positions,
      but also allow for overall spatial compactness. The latter was shown to be
      disrupted by random synonymous mutations, a disruption which can consequently
      negatively affect genome encapsidation. In this study, we use three mutation
      schemes with different degrees of locality to mutate the genomes of phage MS2 and
      Brome Mosaic virus in order to understand the observed sensitivity of the global
      compactness of their folds. We find that mutating local stretches of their
      genomes' sequence or structure is less disruptive to their compactness compared
      to inducing randomly-distributed mutations. Our findings are indicative of a
      mechanism for the conservation of compactness acting on a global scale of the
      genomes, and have several implications for understanding the interplay between
      local and global architecture of viral RNA genomes.

PMID- 29334365
TI  - 12th FluoroFest International Workshop April 24-26, 2017.

PMID- 29334366
TI  - Modified Colistin Regimen for Critically Ill Patients with Acute Renal Impairment
      and Continuous Renal Replacement Therapy.
AB  - Colistin is a last resort antibiotic to treat multidrug-resistant Gram-negative
      bacteria infections. Colistin is administered intravenously in the form of its
      inactive prodrug colistin methanesulfonate (CMS). For patients with acute kidney
      impairment and continuous renal replacement therapy high extracorporeal clearance
      may cause a substantial removal of active colistin from the bloodstream,
      eventually decreasing its antibacterial efficacy. Currently recommended doses of
      CMS may therefore be inadequate for these patients. We report on the potential
      value of a modified regimen that adopts a loading dose of CMS (bolus of 9 MU vs.
      conventional 3 MU every 8 h), followed by maintenance (3 MU every 8 h).
      Preliminary pharmacokinetic evidence for the feasibility and efficacy of this
      regimen is described for 2 patients.

PMID- 29334367
TI  - Unmanipulated haploidentical transplantation conditioning with busulfan,
      cyclophosphamide and anti-thymoglobulin for adult severe aplastic anaemia.
AB  - We conducted a retrospective analysis to evaluate outcomes of haploidentical
      transplantation in adult severe aplastic anaemia (SAA) patients. Fifty-one adults
      received haploidentical transplantation between May 2011 and December 2016.
      Patients were administered busulfan (Bu), cyclophosphamide (Cy) and anti
      thymoglobulin (ATG) as conditioning regimens, followed by bone marrow and
      peripheral blood transplantation. The patients' median age was 25 years. Forty
      nine patients survived for more than 28 days and all achieved donor myeloid
      engraftment. The median time for myeloid engraftment and platelet recovery was 13
      days (range, 10-21) and 17.5 (range, 7-101) days. The cumulative incidence (CI)
      of grade II-IV and III-IV acute GvHD) was 20.00+/-0.33% and 6.00+/-0.12%,
      respectively. The incidence of chronic GvHD was 14.00+/-0.36% and 25.90+/-0.71%,
      and that of moderate-severe chronic GvHD was 2.51+/-0.06% and 6.92+/-0.25% at 1
      and 3 years, respectively. The 3-year estimated overall survival and failure-free
      survival were both 83.5+/-5.4% with a median follow-up of 21.1 months.
      Multivariate analysis showed hematopoietic cell transplantation-specific
      comorbidity index (HCT-CI) score of ?3 was significantly associated with worse
      outcome. Haploidentical transplantation conditioning including Bu/Cy/ATG was a
      safe and effective strategy for adult SAA patients, and HCT-CI might be an
      outcome predictor in these patients.

PMID- 29334368
TI  - Visualizing detailed postdoctoral employment trends using a new career outcome
      taxonomy.

PMID- 29334369
TI  - Dual gene activation and knockout screen reveals directional dependencies in
      genetic networks.
AB  - Understanding the direction of information flow is essential for characterizing
      how genetic networks affect phenotypes. However, methods to find genetic
      interactions largely fail to reveal directional dependencies. We combine two
      orthogonal Cas9 proteins from Streptococcus pyogenes and Staphylococcus aureus to
      carry out a dual screen in which one gene is activated while a second gene is
      deleted in the same cell. We analyze the quantitative effects of activation and
      knockout to calculate genetic interaction and directionality scores for each gene
      pair. Based on the results from over 100,000 perturbed gene pairs, we reconstruct
      a directional dependency network for human K562 leukemia cells and demonstrate
      how our approach allows the determination of directionality in activating genetic
      interactions. Our interaction network connects previously uncharacterized genes
      to well-studied pathways and identifies targets relevant for therapeutic
      intervention.

PMID- 29334370
TI  - Scaffolds that mimic antigen-presenting cells enable ex vivo expansion of primary
      T cells.
AB  - Therapeutic ex vivo T-cell expansion is limited by low rates and T-cell products
      of limited functionality. Here we describe a system that mimics natural antigen
      presenting cells (APCs) and consists of a fluid lipid bilayer supported by
      mesoporous silica micro-rods. The lipid bilayer presents membrane-bound cues for
      T-cell receptor stimulation and costimulation, while the micro-rods enable
      sustained release of soluble paracrine cues. Using anti-CD3, anti-CD28, and
      interleukin-2, we show that the APC-mimetic scaffolds (APC-ms) promote two- to
      tenfold greater polyclonal expansion of primary mouse and human T cells compared
      with commercial expansion beads (Dynabeads). The efficiency of expansion depends
      on the density of stimulatory cues and the amount of material in the starting
      culture. Following a single stimulation, APC-ms enables antigen-specific
      expansion of rare cytotoxic T-cell subpopulations at a greater magnitude than
      autologous monocyte-derived dendritic cells after 2 weeks. APC-ms support over
      fivefold greater expansion of restimulated CD19 CAR-T cells than Dynabeads, with
      similar efficacy in a xenograft lymphoma model.

PMID- 29334371
TI  - Cooperative targeting of melanoma heterogeneity with an AXL antibody-drug
      conjugate and BRAF/MEK inhibitors.
AB  - Intratumor heterogeneity is a key factor contributing to therapeutic failure and,
      hence, cancer lethality. Heterogeneous tumors show partial therapy responses,
      allowing for the emergence of drug-resistant clones that often express high
      levels of the receptor tyrosine kinase AXL. In melanoma, AXL-high cells are
      resistant to MAPK pathway inhibitors, whereas AXL-low cells are sensitive to
      these inhibitors, rationalizing a differential therapeutic approach. We developed
      an antibody-drug conjugate, AXL-107-MMAE, comprising a human AXL antibody linked
      to the microtubule-disrupting agent monomethyl auristatin E. We found that AXL
      107-MMAE, as a single agent, displayed potent in vivo anti-tumor activity in
      patient-derived xenografts, including melanoma, lung, pancreas and cervical
      cancer. By eliminating distinct populations in heterogeneous melanoma cell pools,
      AXL-107-MMAE and MAPK pathway inhibitors cooperatively inhibited tumor growth.
      Furthermore, by inducing AXL transcription, BRAF/MEK inhibitors potentiated the
      efficacy of AXL-107-MMAE. These findings provide proof of concept for the premise
      that rationalized combinatorial targeting of distinct populations in
      heterogeneous tumors may improve therapeutic effect, and merit clinical
      validation of AXL-107-MMAE in both treatment-naive and drug-resistant cancers in
      mono- or combination therapy.

PMID- 29334372
TI  - Pharmacological blockade of ASCT2-dependent glutamine transport leads to
      antitumor efficacy in preclinical models.
AB  - The unique metabolic demands of cancer cells underscore potentially fruitful
      opportunities for drug discovery in the era of precision medicine. However,
      therapeutic targeting of cancer metabolism has led to surprisingly few new drugs
      to date. The neutral amino acid glutamine serves as a key intermediate in
      numerous metabolic processes leveraged by cancer cells, including biosynthesis,
      cell signaling, and oxidative protection. Herein we report the preclinical
      development of V-9302, a competitive small molecule antagonist of transmembrane
      glutamine flux that selectively and potently targets the amino acid transporter
      ASCT2. Pharmacological blockade of ASCT2 with V-9302 resulted in attenuated
      cancer cell growth and proliferation, increased cell death, and increased
      oxidative stress, which collectively contributed to antitumor responses in vitro
      and in vivo. This is the first study, to our knowledge, to demonstrate the
      utility of a pharmacological inhibitor of glutamine transport in oncology,
      representing a new class of targeted therapy and laying a framework for paradigm
      shifting therapies targeting cancer cell metabolism.

PMID- 29334374
TI  - Transitory presence of myeloid-derived suppressor cells in neonates is critical
      for control of inflammation.
AB  - Myeloid-derived suppressor cells (MDSCs) are pathologically activated and
      relatively immature myeloid cells that have been implicated in the immunological
      regulation of many pathologic conditions. Phenotypically and morphologically,
      MDSCs are similar to neutrophils (PMN-MDSCs) and monocytes (M-MDSCs). However,
      they have potent suppressive activity and distinct gene expression profiles and
      biochemical characteristics. No or very few MDSCs are observed in steady-state
      physiological conditions. Therefore, until recently, accumulation of MDSCs was
      considered a consequence of pathological processes or pregnancy. Here, we report
      that MDSCs with a potent ability to suppress T cells are present during the first
      weeks of life in mice and humans. MDSC suppressive activity was triggered by
      lactoferrin and mediated by nitric oxide, PGE2, and S100A9 and S100A8 proteins.
      MDSCs from newborns had a transcriptome similar to that of tumor MDSCs, but with
      strong upregulation of an antimicrobial gene network, and had potent
      antibacterial activity. MDSCs played a critical role in control of experimental
      necrotizing enterocolitis (NEC) in newborn mice. MDSCs in infants with very low
      weight, who are prone to NEC, had lower MDSC levels and suppressive activity than
      did infants with normal weight. Thus, the transitory presence of MDSCs may be
      critical for regulation of inflammation in newborns.

PMID- 29334373
TI  - Prevention of tuberculosis in rhesus macaques by a cytomegalovirus-based vaccine.
AB  - Despite widespread use of the bacille Calmette-Guerin (BCG) vaccine, tuberculosis
      (TB) remains a leading cause of global mortality from a single infectious agent
      (Mycobacterium tuberculosis or Mtb). Here, over two independent Mtb challenge
      studies, we demonstrate that subcutaneous vaccination of rhesus macaques (RMs)
      with rhesus cytomegalovirus vectors encoding Mtb antigen inserts (hereafter
      referred to as RhCMV/TB)-which elicit and maintain highly effector
      differentiated, circulating and tissue-resident Mtb-specific CD4+ and CD8+ memory
      T cell responses-can reduce the overall (pulmonary and extrapulmonary) extent of
      Mtb infection and disease by 68%, as compared to that in unvaccinated controls,
      after intrabronchial challenge with the Erdman strain of Mtb at ~1 year after the
      first vaccination. Fourteen of 34 RhCMV/TB-vaccinated RMs (41%) across both
      studies showed no TB disease by computed tomography scans or at necropsy after
      challenge (as compared to 0 of 17 unvaccinated controls), and ten of these RMs
      were Mtb-culture-negative for all tissues, an exceptional long-term vaccine
      effect in the RM challenge model with the Erdman strain of Mtb. These results
      suggest that complete vaccine-mediated immune control of highly pathogenic Mtb is
      possible if immune effector responses can intercept Mtb infection at its earliest
      stages.

PMID- 29334375
TI  - A small-molecule inhibitor of the ubiquitin activating enzyme for cancer
      treatment.
AB  - The ubiquitin-proteasome system (UPS) comprises a network of enzymes that is
      responsible for maintaining cellular protein homeostasis. The therapeutic
      potential of this pathway has been validated by the clinical successes of a
      number of UPS modulators, including proteasome inhibitors and immunomodulatory
      imide drugs (IMiDs). Here we identified TAK-243 (formerly known as MLN7243) as a
      potent, mechanism-based small-molecule inhibitor of the ubiquitin activating
      enzyme (UAE), the primary mammalian E1 enzyme that regulates the ubiquitin
      conjugation cascade. TAK-243 treatment caused depletion of cellular ubiquitin
      conjugates, resulting in disruption of signaling events, induction of proteotoxic
      stress, and impairment of cell cycle progression and DNA damage repair pathways.
      TAK-243 treatment caused death of cancer cells and, in primary human xenograft
      studies, demonstrated antitumor activity at tolerated doses. Due to its
      specificity and potency, TAK-243 allows for interrogation of ubiquitin biology
      and for assessment of UAE inhibition as a new approach for cancer treatment.

PMID- 29334377
TI  - Detecting hierarchical genome folding with network modularity.
AB  - Mammalian genomes are folded in a hierarchy of compartments, topologically
      associating domains (TADs), subTADs and looping interactions. Here, we describe
      3DNetMod, a graph theory-based method for sensitive and accurate detection of
      chromatin domains across length scales in Hi-C data. We identify nested,
      partially overlapping TADs and subTADs genome wide by optimizing network
      modularity and varying a single resolution parameter. 3DNetMod can be applied
      broadly to understand genome reconfiguration in development and disease.

PMID- 29334378
TI  - Supermultiplexed optical imaging and barcoding with engineered polyynes.
AB  - Optical multiplexing has a large impact in photonics, the life sciences and
      biomedicine. However, current technology is limited by a 'multiplexing ceiling'
      from existing optical materials. Here we engineered a class of polyyne-based
      materials for optical supermultiplexing. We achieved 20 distinct Raman
      frequencies, as 'Carbon rainbow', through rational engineering of conjugation
      length, bond-selective isotope doping and end-capping substitution of polyynes.
      With further probe functionalization, we demonstrated ten-color organelle imaging
      in individual living cells with high specificity, sensitivity and photostability.
      Moreover, we realized optical data storage and identification by combinatorial
      barcoding, yielding to our knowledge the largest number of distinct spectral
      barcodes to date. Therefore, these polyynes hold great promise in live-cell
      imaging and sorting as well as in high-throughput diagnostics and screening.

PMID- 29334376
TI  - Positively selected enhancer elements endow osteosarcoma cells with metastatic
      competence.
AB  - Metastasis results from a complex set of traits acquired by tumor cells, distinct
      from those necessary for tumorigenesis. Here, we investigate the contribution of
      enhancer elements to the metastatic phenotype of osteosarcoma. Through epigenomic
      profiling, we identify substantial differences in enhancer activity between
      primary and metastatic human tumors and between near isogenic pairs of highly
      lung metastatic and nonmetastatic osteosarcoma cell lines. We term these regions
      metastatic variant enhancer loci (Met-VELs). Met-VELs drive coordinated waves of
      gene expression during metastatic colonization of the lung. Met-VELs cluster
      nonrandomly in the genome, indicating that activity of these enhancers and
      expression of their associated gene targets are positively selected. As evidence
      of this causal association, osteosarcoma lung metastasis is inhibited by global
      interruptions of Met-VEL-associated gene expression via pharmacologic BET
      inhibition, by knockdown of AP-1 transcription factors that occupy Met-VELs, and
      by knockdown or functional inhibition of individual genes activated by Met-VELs,
      such as that encoding coagulation factor III/tissue factor (F3). We further show
      that genetic deletion of a single Met-VEL at the F3 locus blocks metastatic cell
      outgrowth in the lung. These findings indicate that Met-VELs and the genes they
      regulate play a functional role in metastasis and may be suitable targets for
      antimetastatic therapies.

PMID- 29334379
TI  - Highly parallel direct RNA sequencing on an array of nanopores.
AB  - Sequencing the RNA in a biological sample can unlock a wealth of information,
      including the identity of bacteria and viruses, the nuances of alternative
      splicing or the transcriptional state of organisms. However, current methods have
      limitations due to short read lengths and reverse transcription or amplification
      biases. Here we demonstrate nanopore direct RNA-seq, a highly parallel, real
      time, single-molecule method that circumvents reverse transcription or
      amplification steps. This method yields full-length, strand-specific RNA
      sequences and enables the direct detection of nucleotide analogs in RNA.

PMID- 29334380
TI  - Light-activated chemical probing of nucleobase solvent accessibility inside
      cells.
AB  - The discovery of functional RNAs that are critical for normal and disease
      physiology continues to expand at a breakneck pace. Many RNA functions are
      controlled by the formation of specific structures, and an understanding of each
      structural component is necessary to elucidate its function. Measuring solvent
      accessibility intracellularly with experimental ease is an unmet need in the
      field. Here, we present a novel method for probing nucleobase solvent
      accessibility, Light Activated Structural Examination of RNA (LASER). LASER
      depends on light activation of a small molecule, nicotinoyl azide (NAz), to
      measure solvent accessibility of purine nucleobases. In vitro, this technique
      accurately monitors solvent accessibility and identifies rapid structural changes
      resulting from ligand binding in a metabolite-responsive RNA. LASER probing can
      further identify cellular RNA-protein interactions and unique intracellular RNA
      structures. Our photoactivation technique provides an adaptable framework to
      structurally characterize solvent accessibility of RNA in many environments.

PMID- 29334382
TI  - A de novo enzyme catalyzes a life-sustaining reaction in Escherichia coli.
AB  - Producing novel enzymes that are catalytically active in vitro and biologically
      functional in vivo is a key goal of synthetic biology. Here we describe Syn-F4,
      the first de novo protein that meets both criteria. Purified Syn-F4 hydrolyzes
      the siderophore ferric enterobactin, and expression of Syn-F4 allows an inviable
      strain of Escherichia coli to grow in iron-limited medium. These findings
      demonstrate that entirely new sequences can provide life-sustaining enzymatic
      functions in living organisms.

PMID- 29334383
TI  - A simple method for determining the ligand affinity toward a zinc-enzyme model by
      using a TAMRA/TAMRA interaction.
AB  - Thiolate coordination to zinc(ii) ions occurs widely in such functional
      biomolecules as zinc enzymes or zinc finger proteins. Here, we introduce a simple
      method for determining the affinity of ligands toward the zinc-enzyme active
      center model tetramethylrhodamine (TAMRA)-labeled 1,4,7,10-tetraazacyclododecane
      (cyclen)-zinc(ii) complex (TAMRA-ZnL). The 1 : 1 complexation of TAMRA-labeled
      cysteine (TAMRA-Cys) with TAMRA-ZnL (each at 2.5 MUM), in which the TAMRA
      moieties approach one another closely, induces remarkable changes in the visible
      absorption and fluorescence spectra at pH 7.4 and 25  degrees C. The 1 : 1
      complex formation constant (K = [thiolate-bound zinc(ii) complex]/[uncomplexed
      TAMRA-ZnL][uncomplexed TAMRA-Cys], M-1) was determined to be 106.7 M-1 from a
      Job's plot of the absorbances at 552 nm. By a ligand-competition method with the
      1 : 1 complexation equilibrium, analogous K values for thiol-containing ligands,
      such as N-acetyl-l-cysteine, l-glutathione, and N-acetyl-l-cysteinamide, were
      evaluated to have similar values of about 104 M-1. As a result of the ligand
      affinities to TAMRA-ZnL, nonlabeled zinc(ii)-cyclen induced remarkable
      stabilization of the reduced form of l-glutathione and a cysteine-containing
      enolase peptide to aerial oxidation in aqueous solution at pH 7.4 and 25  degrees
      C.

PMID- 29334381
TI  - The molecular basis of subtype selectivity of human kinin G-protein-coupled
      receptors.
AB  - G-protein-coupled receptors (GPCRs) are the most important signal transducers in
      higher eukaryotes. Despite considerable progress, the molecular basis of subtype
      specific ligand selectivity, especially for peptide receptors, remains unknown.
      Here, by integrating DNP-enhanced solid-state NMR spectroscopy with advanced
      molecular modeling and docking, the mechanism of the subtype selectivity of human
      bradykinin receptors for their peptide agonists has been resolved. The conserved
      middle segments of the bound peptides show distinct conformations that result in
      different presentations of their N and C termini toward their receptors. Analysis
      of the peptide-receptor interfaces reveals that the charged N-terminal residues
      of the peptides are mainly selected through electrostatic interactions, whereas
      the C-terminal segments are recognized via both conformations and interactions.
      The detailed molecular picture obtained by this approach opens a new gateway for
      exploring the complex conformational and chemical space of peptides and peptide
      analogs for designing GPCR subtype-selective biochemical tools and drugs.

PMID- 29334384
TI  - Micrometer-sized dihydrogenphosphate-intercalated layered double hydroxides:
      synthesis, selective infrared absorption properties, and applications as
      agricultural films.
AB  - High-performance heat-retention agents for multifunctional green agricultural
      films are today largely suitable to increase the production yield as well as to
      save energy. Here, an adapted ammonia releasing hydrothermal method was used to
      produce a series of micrometer-sized carbonate-layered double hydroxide (CO3-LDH)
      precursors of sizes ranging from 1.32 MUm to 8.64 MUm by simply adjusting the
      feeding Mg2+ concentration from 0.80 mol L-1 to 0.20 mol L-1. From these pristine
      LDH materials, MUm-sized dihydrogenphosphate-intercalated LDHs (H2PO4-LDHs) were
      prepared by an anion-exchange method. The structure, the platelet size, and the
      associated selective IR absorption properties of the H2PO4-LDH and the derivative
      H2PO4-LDH/EVA composite as well as the related visible transmittance and the
      photostability of the H2PO4-LDH/EVA film were investigated. The results show that
      the selective IR absorption in the wavelength range of 7-14 MUm enabling the heat
      retention of the H2PO4-LDHs and H2PO4-LDH/EVA composites depends on the
      corresponding number-averaged particle size of H2PO4-LDH in the range of 2.01 MUm
      to 8.80 MUm. Compared with EVA, the H2PO4-LDH/EVA composites demonstrate a
      significant improvement of selective IR absorption, while maintaining acceptable
      visible transmittance, and similar photostability. An optimized particle size of
      H2PO4-LDH of ca. 5.85 MUm leads to 60% selective IR absorption and 64% selective
      IR absorption when dispersed in EVA, while the polymer free of filler exhibits
      less than 50% absorption in the 7-14 MUm IR domain.

PMID- 29334385
TI  - Mechanical stability of a nanotube from monolayer black phosphorus with the [110]
      direction as the tube's circumference or generatrix.
AB  - The mechanical properties of black phosphorus (BP) are anisotropic.
      Correspondingly, the properties of the nanotubes formed by bending the same BP
      ribbon along different directions are different as well. When bending the ribbon
      along the [110] direction (i.e., stair direction), or along its perpendicular
      direction (i.e., ps-direction), s- or ps-BPNT can be obtained. The two types of
      BPNTs are investigated via molecular dynamics (MD) simulations on their thermal
      and mechanical properties. The results indicate that, for the thermal stability
      of the s-BPNTs with similar diameters, s-BPNT is weaker than a-BPNTs (armchair
      type) but stronger than ps-BPNT, and z-BPNT (zigzag type) is the weakest one. In
      general, a-BPNT has larger compressive or tensile strength, while s-BPNT and ps
      BPNT can bear larger deformation. Under uniaxial compression, s-BPNT has two
      different breaking patterns at different temperatures. The peculiar properties
      illustrate the wider application of BPNTs in nanodevices under large deformation.

PMID- 29334386
TI  - Organic-inorganic hybrids having a talc-like structure as suitable hosts to guest
      a wide range of species.
AB  - The sol-gel process involving hydrolysis and condensation reactions is an
      attractive way to form siloxane based hybrid materials since it is a one-step
      method performed under mild conditions. Organic-inorganic hybrids having a talc
      like structure (TLH) can be obtained using this procedure starting from
      organotrialkoxysilanes having the formula R-Si(OR')3 (where R stands for an
      organic moiety and R' for a methyl or ethyl group) with different
      functionalities, an aqueous or ethanolic solution of a magnesium salt, and in
      some cases, an aqueous solution of sodium hydroxide. In this way, the organic
      chains are covalently bonded to the silicon of the tetrahedral sheets, pointing
      toward the interlayer space. The interesting feature in this case is that as many
      organotrialkoxysilanes are on the market, a wide range of organic moieties can be
      introduced in the interlayer space leading to applications in various fields.
      This review highlights the latest trends and the multifaceted applications of
      these functional layered compounds.

PMID- 29334387
TI  - A utility for organoleads: selective alkyl and aryl group transfer to tin.
AB  - Me4Pb and Ph4Pb readily transfer methyl or phenyl groups to an equivalent molar
      ratio of tin(iv) chlorides in the order SnCl4 > MeSnCl3 > Me2SnCl2 > Me3SnCl,
      often in a selective manner. Me3PbCl and Ph3PbCl specifically transfer a single
      methyl/phenyl group under the same reaction conditions to produce recovered
      yields in >75%. Specific transfer of 2 methyl groups from PbMe4 can be achieved
      at elevated temperatures and/or a 2 : 1 molar ratio Pb : Sn.

PMID- 29334388
TI  - Catalytic (de)hydrogenation promoted by non-precious metals - Co, Fe and Mn:
      recent advances in an emerging field.
AB  - Catalytic hydrogenation and dehydrogenation reactions form the core of the modern
      chemical industry. This vast class of reactions is found in any part of chemical
      synthesis starting from the milligram-scale exploratory organic chemistry to the
      multi-ton base chemicals production. Noble metal catalysis has long been the key
      driving force in enabling these transformations with carbonyl substrates and
      their nitrogen-containing counterparts. This review is aimed at introducing the
      reader to the remarkable progress made in the last three years in the development
      of base metal catalysts for hydrogenations and dehydrogenative transformations.

PMID- 29334389
TI  - Effect of coordination geometry on the magnetic properties of a series of Ln2 and
      Ln4 hydroxo clusters.
AB  - A series of three isostructural tetranuclear complexes with the general molecular
      formula [Ln4(MU3-OH)4(L)4(MU2-piv)4(MeOH)4] (Ln = Gd 1, Dy 2 and Ho 3; LH = [1,3
      bis(o-methoxyphenyl)-propane-1,3-dione]) were isolated and unambiguously
      characterized by single crystal XRD. Under similar reaction conditions, simply
      changing the co-ligand from pivalate to 2,6-bis(hydroxymethyl)-p-cresol (LH'3)
      led to the isolation of dinuclear Ln(iii) complexes with the general molecular
      formula [Ln2(L)4(MU2-LH'2)2].4DMF (Ln = Gd 4, Dy 5 and Ho 6). Direct current
      magnetic susceptibility data studies on the polycrystalline sample of 1-6 and the
      results reveal the existence of weak antiferromagnetic exchange interactions
      between the lanthanide ions in 1 which is evident from the spin Hamiltonian (SH)
      parameters (J1 = -0.055 cm-1 and g = 2.01) extracted by fitting chiMT(T). On the
      other hand, though complex 4 exhibits weak antiferromagnetic coupling (J1 = 
      0.048 cm-1 and g = 1.99) between the Gd(iii) ions, the chiMT(T) data of complexes
      5 and 6 unambiguously disclose the presence of ferromagnetic interactions between
      Dy(iii) and Tb(iii) ions at lower temperature. Magnetization relaxation dynamics
      studies performed on 2 show frequency dependent out-of-phase susceptibility
      signals in the presence of an optimum external magnetic field of 0.5 kOe. In
      contrast, complex 5 shows slow magnetization relaxation with an effective energy
      barrier (Ueff) of 38.17 cm-1 with a pre-exponential factor (tau0) of 1.85 * 10-6
      s. The magnetocaloric effect (MCE) of complexes 1 and 4 was extracted from the
      detailed magnetization measurement and the change in the magnetic entropy (
      DeltaSm) of 1 and 4 was found to be 25.57 J kg-1 K-1 and 12.93 J kg-1 K-1,
      respectively, at 3.0 K for DeltaH = 70 kOe.

PMID- 29334390
TI  - Smartphone integrated optoelectrowetting (SiOEW) for on-chip sample processing
      and microscopic detection of water quality.
AB  - With the increasing capabilities and ubiquity of smartphones and their associated
      digital cameras, this study presents a smartphone integrated optoelectrowetting
      (SiOEW) device as a simple, portable tool capable of on-chip water sample
      preparation and microscopic detection of the target cells in water samples, which
      significantly reduce the detection time and the labor cost required for water
      quality monitoring. A commercially available smartphone is used as a low
      intensity portable light source to perform optoelectrowetting (OEW)-based
      microfluidic operations such as droplet transportation, merging, mixing, and
      immobilization on a hydrophobic detection zone. Furthermore, a built-in
      smartphone camera allows on-chip microscopic detection of water quality with a
      45* magnification. We have experimentally demonstrated that the SiOEW platform is
      able not only to automate the sample processing of marine water including the
      target algae cells (Amphiprora sp.) and staining reagents fluorescein diacetate
      (FDA) and 5-chloromethylfluorescein diacetate (CMFDA), but also detect the
      fluorescence signals emitted from the target cells in water samples and count
      their populations. Using the smartphone, the collected information (e.g. the
      location of the water sample collected and the time it was detected, the number
      of the target cells, etc.) can be rapidly and wirelessly shared with a central
      host such as an environmental regulation agency for real-time monitoring and
      further management of water quality.

PMID- 29334392
TI  - Control of collagen gel mechanical properties through manipulation of gelation
      conditions near the sol-gel transition.
AB  - The ability to control the mechanical properties of cell culture environments is
      known to influence cell morphology, motility, invasion and differentiation. The
      present work shows that it is possible to control the mechanical properties of
      collagen gels by manipulating gelation conditions near the sol gel transition.
      This manipulation is accomplished by performing gelation in two stages at
      different temperatures. The mechanical properties of the gel are found to be
      strongly dependent on the duration and temperature of the first stage. In the
      second stage the system is quickly depleted of free collagen which self assembles
      into a highly branched network characteristic of gelation at the higher
      temperature (37  degrees C). An important aspect of the present work is the use
      of advanced rheometric techniques to assess the transition point between
      viscoelastic liquid and viscoelastic solid behaviour which occurs upon
      establishment of a sample spanning network at the gel point. The gel time at the
      stage I temperature is found to indicate the minimum time that the gelling
      collagen sample must spend under stage I conditions before the two stage gelation
      procedure generates an enhancement of mechanical properties. Further, the
      Fractional Maxwell Model is found to provide an excellent description of the time
      dependent mechanical properties of the mature collagen gels.

PMID- 29334393
TI  - Facile fabrication and characterization of two-dimensional bismuth(iii) sulfide
      nanosheets for high-performance photodetector applications under ambient
      conditions.
AB  - Two-dimensional (2D) bismuth(iii) sulfide (Bi2S3) nanosheets as non-toxic
      graphene-like nanomaterials were successfully fabricated by a facile liquid phase
      exfoliation (LPE) method. A robust photodetector employing a Bi2S3 nanosheet film
      has been fabricated for the first time via a facile fabrication process on an ITO
      coated glass. UV-Vis and Raman spectroscopy techniques were carried out and they
      confirmed the inherent optical and physical properties of Bi2S3 nanosheets.
      Photoelectrochemical (PEC) measurements demonstrate that a significantly higher
      photocurrent density (42 MUA cm-2) and enhanced photoresponsivity (210 MUA W-1),
      at a lower bias potential in alkaline solution, of the Bi2S3 nanosheet-based
      photodetector are achieved, compared with those of other 2D nanomaterial-based
      photodetectors under light irradiation. Furthermore, the as-prepared Bi2S3
      nanosheet-based photodetector not only exhibits an appropriate capacity of self
      driven broadband and high-performance photoresponse but also displays strong long
      term stability of the ON/OFF switching behaviour without any external protection
      in alkaline solutions. Because of facile synthesis via a LPE method, a higher
      photocurrent density and photoresponsivity, self-driven performance and long-term
      stability of the Bi2S3 nanosheet-based photodetector at a lower bias potential in
      alkaline solutions, the present work can provide fundamental acknowledgement of
      the high performance of this new kind of PEC-type 2D nanosheet-based
      photodetector.

PMID- 29334394
TI  - Substitution of the laser borane anti-B18H22 with pyridine: a structural and
      photophysical study of some unusually structured macropolyhedral boron hydrides.
AB  - Reaction of anti-B18H221 with pyridine in neutral solvents gives sparingly
      soluble B16H18-3',8'-Py23a as the major product (ca. 53%) and B18H20-6',9'-Py22
      (ca. 15%) as the minor product, with small quantities of B18H20-8'-Py 4 (ca. 1%)
      also being formed. The three new compounds 2, 3a and 4 are characterized by
      single-crystal X-ray diffraction analyses and by multinuclear multiple-resonance
      NMR spectroscopy. Compound 2 is of ten-vertex nido:ten-vertex arachno two-atoms
      in-common architecture, long postulated for a species with borons-only cluster
      constitution, but previously elusive. Compound 3a is of unprecedented ten-vertex
      nido:eight-vertex arachno two-atoms-in-common architecture. The single-crystal X
      ray diffraction analysis for the picoline derivative B16H18(NC5H4Me)23b,
      similarly obtained, is also presented. B18H20Py 4 is also previously unreported
      but is of known ten-vertex nido:ten-vertex nido two-atoms-in-common architecture
      of anti configuration, but now with the pyridine ligand positioned differently to
      other reported examples of B18H20L compounds. Factors behind the remarkably low
      solubility of 3a and 3b are elucidated in terms of electrostatic potential (ESP)
      calculations, polarity, and van der Waals complementarities. In view of
      contemporary developing high interest in the fluorescent properties of
      macropolyhedral boron-containing species, a detailed assessment of the
      photophysical characteristics of 3a and 4 is also presented. In contrast to the
      thermochromic fluorescence of 2 (from 620 nm brick-red at room temperature to 585
      nm yellow at 8 K, quantum yield 0.15), compound 3a is only weakly phosphorescent
      in the yellow region (590 nm, quantum yield 0.01), whereas compound 4 exhibits no
      luminescence. The far more photoactive nature of compound 2 is associated with S1
      excited-state minima structures that differ from each other only by the relative
      rotational positions of the pyridine substituents on its disubstituted ten-vertex
      {arachno-B10Py2}-subcluster. The wavelength and relative intensity of
      fluorescence from these structures depends on the rotational positions of the
      pyridine ligands, which in turn are influenced by temperature and/or rotational
      inhibition in the solid-state.

PMID- 29334395
TI  - Probing the geometry of copper and silver adatoms on magnetite: quantitative
      experiment versus theory.
AB  - Accurately modelling the structure of a catalyst is a fundamental prerequisite
      for correctly predicting reaction pathways, but a lack of clear experimental
      benchmarks makes it difficult to determine the optimal theoretical approach.
      Here, we utilize the normal incidence X-ray standing wave (NIXSW) technique to
      precisely determine the three dimensional geometry of Ag1 and Cu1 adatoms on
      Fe3O4(001). Both adatoms occupy bulk-continuation cation sites, but with a
      markedly different height above the surface (0.43 +/- 0.03 A (Cu1) and 0.96 +/-
      0.03 A (Ag1)). HSE-based calculations accurately predict the experimental
      geometry, but the more common PBE + U and PBEsol + U approaches perform poorly.

PMID- 29334396
TI  - Towards the continuous production of Pt-based heterogeneous catalysts using
      microfluidic systems.
AB  - The continuous production of Pt-based heterogeneous catalysts based on ultra
      small (<2 nm) noble metal nanoparticles deposited on mesoporous ordered silica
      and their catalytic activity in VOC abatement are here reported. Microfluidic
      reactors can be used not only to enable the fast and controlled production of
      ultra-small Pt nanoparticles (NPs), but also alloyed NPs including PtPd, PtRu and
      PtRh can be formed in short residence times (between 60 s and 5 min). A novel
      continuous and homogeneous loading of these catalytic NPs on SBA-15 used as a
      mesoporous support is also here reported. This procedure eases the NP loading and
      minimizes washing post-treatments. A 12-fold decrease in the synthesis time was
      obtained when using this microfluidic reactor compared to the traditional batch
      production of Pt NPs. Microflow and batch type reactors yielded a Pt precursor
      conversion to generate Pt NPs with a 90% and 85% yield, respectively. Under the
      same conditions, the productivity of the microfluidic system (27 mg Pt NPs per h)
      was twice the one achieved in the conventional batch type reactor. The catalytic
      performance of the supported catalysts separately prepared by microfluidics and
      by conventional impregnation under the same conditions and with the same noble
      metal loading was also compared in the n-hexane abatement as a model of VOCs.
      Both catalysts were active in the VOC oxidation reaction but a 95% reduction in
      the catalyst synthesis time was obtained when using the catalysts produced in the
      microfluidic platform. For this reaction a long-term activity test was
      successfully carried out at 175  degrees C during 30 h on stream using the
      heterogeneous catalyst prepared by using the flow reactor.

PMID- 29334398
TI  - Formation of shelf stable Pickering high internal phase emulsions (HIPE) through
      the inclusion of whey protein microgels.
AB  - High internal phase emulsions (HIPE) prepared using whey protein microgels (WPMs)
      as a surfactant were demonstrated to have substantially higher stability than
      HIPEs prepared using similar loadings of non-gelled whey protein isolate (WPI) or
      Tween 20. Microgel colloids were prepared from WPI solutions by heat treatment at
      85  degrees C in a narrow pH range (5.8-6.0) to particle sizes of approximately
      90, 160 and 350 nm in diameter. zeta-potentials of the WPM increased in
      negativity with decreasing particle size from -7.4 +/- 2.5 down to -21.1 +/- 0.9
      at 90 nm. All WPMs conferred high stability to corn oil based HIPE when used as
      an emulsifier. Light microscopy and cryo-scanning electron microscopy showed that
      both increasing WPM concentration and decreasing WPM particle size produced
      increasingly smaller and more hexagonally shaped corn oil emulsion droplets; WPI
      and Tween 20 based HIPE droplets were generally smaller and spherical in shape.
      The HIPE (75% w/w corn oil) produced with 1% (w/w) WPM as an emulsifier showed
      stability through 6 months storage at 4  degrees C at all WPM sizes tested, while
      the HIPE prepared with 1% (w/w) WPI or Tween 20 exhibited significant creaming.
      WPM and WPI based HIPE both showed thermal stability at 70  degrees C and 95 
      degrees C while the heating of Tween 20 based HIPE resulted in droplet
      coalescence and oil-phase separation. HIPE production with WPMs significantly
      improved the viscoelastic properties of the HIPE, imparting drastic increases in
      yield stress, critical stress, complex modulus and elastic modulus over HIPE
      prepared with WPI or Tween 20. The more rigid rheology of the WPM HIPE indicated
      by these data is likely the primary mechanism driving the improved stability of
      these emulsions.

PMID- 29334397
TI  - Recombinant phosphatidylserine-binding nanobodies for targeting of extracellular
      vesicles to tumor cells: a plug-and-play approach.
AB  - Extracellular vesicles (EVs) are increasingly being recognized as candidate drug
      delivery systems due to their ability to functionally transfer biological cargo
      between cells. However, manipulation of targeting properties of EVs through
      engineering of the producer cells can be challenging and time-consuming. As a
      novel approach to confer tumor targeting properties to isolated EVs, we generated
      recombinant fusion proteins of nanobodies against the epidermal growth factor
      receptor (EGFR) fused to phosphatidylserine (PS)-binding domains of lactadherin
      (C1C2). C1C2-nanobody fusion proteins were expressed in HEK293 cells and isolated
      from culture medium with near-complete purity as determined by SDS-PAGE. Fusion
      proteins specifically bound PS and showed no affinity for other common EV
      membrane lipids. Furthermore, C1C2 fused to anti-EGFR nanobodies (EGa1-C1C2)
      bound EGFR with high affinity and competed with binding of its natural ligand
      EGF, as opposed to C1C2 fused to non-targeting control nanobodies (R2-C1C2). Both
      proteins readily self-associated onto membranes of EVs derived from erythrocytes
      and Neuro2A cells without affecting EV size and integrity. EV-bound R2-C1C2 did
      not influence EV-cell interactions, whereas EV-bound EGa1-C1C2 dose-dependently
      enhanced specific binding and uptake of EVs by EGFR-overexpressing tumor cells.
      In conclusion, we developed a novel strategy to efficiently and universally
      confer tumor targeting properties to PS-exposing EVs after their isolation,
      without affecting EV characteristics, circumventing the need to modify EV
      secreting cells. This strategy may also be employed to decorate EVs with other
      moieties, including imaging probes or therapeutic proteins.

PMID- 29334399
TI  - Chondrocyte burst promotes space for mineral expansion.
AB  - Analysis of tissue development from multidisciplinary approaches can result in
      more integrative biological findings, and can eventually allow the development of
      more effective bioengineering methods. In this study, we analyzed the initial
      steps of mineral formation during secondary ossification of mouse femur based on
      biological and bioengineering approaches. We first found that some chondrocytes
      burst near the mineralized area. External factors that could trigger chondrocyte
      burst were then investigated. Chondrocyte burst was shown to be modulated by
      mechanical and osmotic pressure. A hypotonic solution, as well as mechanical
      stress, significantly induced chondrocyte burst. We further hypothesized that
      chondrocyte burst could be associated with space-making for mineral expansion. In
      fact, ex vivo culture of femur epiphysis in hypotonic conditions, or under
      mechanical pressure, enhanced mineral formation, compared to normal culture
      conditions. Additionally, the effect of mechanical pressure on bone formation in
      vivo was investigated by immobilization of mouse lower limbs to decrease the body
      pressure onto the joints. The results showed that limb immobilization suppressed
      bone formation. Together, these results suggest chondrocyte burst as a novel fate
      of chondrocytes, and that manipulation of chondrocyte burst with external mechano
      chemical stimuli could be an additional approach for cartilage and bone tissue
      engineering.

PMID- 29334400
TI  - Oolong tea and LR-White resin: a new method of plant sample preparation for
      transmission electron microscopy.
AB  - Simplifying sample processing, shortening the sample preparation time, and
      adjusting procedures to suitable for new health and safety regulations, these
      issues are the current challenges which electron microscopic examinations need to
      face. In order to resolve these problems, new plant tissue sample processing
      protocols for transmission electron microscopy should be developed. In the
      present study, we chose the LR-White resin-assisted processing protocol for the
      ultrastructural observation of different types of plant tissues. Moreover, we
      explored Oolong tea extract (OTE) as a substitute for UA in staining ultrathin
      sections of plant samples. The results revealed that there was no significant
      difference between the OTE double staining method and the traditional double
      staining method. Furthermore, in some organelles, such as mitochondria in root
      cells of tomatoes and chloroplast in leaf cells of watermelons, the OTE double
      staining method achieved little better results than the traditional double
      staining method. Therefore, OTE demonstrated good potentials in replacing UA as a
      counterstain on ultrathin sections. In addition, sample preparation time was
      significantly shortened and simplified using LR-White resin. This novel protocol
      reduced the time for preparing plant samples, and hazardous reagents in
      traditional method (acetone and UA) were also replaced by less toxic ones
      (ethanol and OTE).

PMID- 29334401
TI  - Unearthing belowground bud banks in fire-prone ecosystems.
AB  - Despite long-time awareness of the importance of the location of buds in plant
      biology, research on belowground bud banks has been scant. Terms such as
      lignotuber, xylopodium and sobole, all referring to belowground bud-bearing
      structures, are used inconsistently in the literature. Because soil efficiently
      insulates meristems from the heat of fire, concealing buds below ground provides
      fitness benefits in fire-prone ecosystems. Thus, in these ecosystems, there is a
      remarkable diversity of bud-bearing structures. There are at least six locations
      where belowground buds are stored: roots, root crown, rhizomes, woody burls,
      fleshy swellings and belowground caudexes. These support many morphologically
      distinct organs. Given their history and function, these organs may be divided
      into three groups: those that originated in the early history of plants and that
      currently are widespread (bud-bearing roots and root crowns); those that also
      originated early and have spread mainly among ferns and monocots (nonwoody
      rhizomes and a wide range of fleshy underground swellings); and those that
      originated later in history and are strictly tied to fire-prone ecosystems (woody
      rhizomes, lignotubers and xylopodia). Recognizing the diversity of belowground
      bud banks is the starting point for understanding the many evolutionary pathways
      available for responding to severe recurrent disturbances.

PMID- 29334402
TI  - Noninvasive reconstruction of placental methylome from maternal plasma DNA:
      Potential for prenatal testing and monitoring.
AB  - OBJECTIVE: During human pregnancy, the DNA methylation of placental tissue is
      highly relevant to the normal growth and development of the fetus; therefore,
      methylomic analysis of the placental tissue possesses high research and clinical
      value in prenatal testing and monitoring. Thus, our aim is to develop an approach
      for reconstruction of the placental methylome, which should be completely
      noninvasive and achieve high accuracy and resolution. RESULTS: We propose a novel
      size-based algorithm, FEtal MEthylome Reconstructor (FEMER), to noninvasively
      reconstruct the placental methylome by genomewide bisulfite sequencing and size
      based analysis of maternal plasma DNA. By applying FEMER on a real clinical
      dataset, we demonstrate that FEMER achieves both high accuracy and resolution,
      thus provides a high-quality view of the placental methylome from maternal plasma
      DNA. FEtal MEthylome Reconstructor could also predict the DNA methylation profile
      of CpG islands with high accuracy, thus shows potential in monitoring of key
      genes involved in placental/fetal development. Source code and testing datasets
      for FEMER are available at http://sunlab.cpy.cuhk.edu.hk/FEMER/. CONCLUSION:
      FEtal MEthylome Reconstructor could enhance the noninvasive fetal/placental
      methylomic analysis and facilitate its application in prenatal testing and
      monitoring.

PMID- 29334403
TI  - Soft tissue volume gain around dental implants using autogenous subepithelial
      connective tissue grafts harvested from the lateral palate or tuberosity area. A
      randomized controlled clinical study.
AB  - AIM: To compare the soft tissue volume gain (VG) around single tooth implants
      with subepithelial connective tissue graft (SCTG) from either the lateral palate
      (LP) or from the tuberosity area (TA). METHODS: Thirty-two patients with 36
      implants with buccal volume deficiencies were randomly assigned to receive SCTG
      from LP (control group/CG) or TA (test group/TG). Clinical parameters were
      recorded. VG was evaluated by stereolithography (STL) image superimposition of
      two intraoral scans (baseline/BL and 3 months after surgery/FU-3). Descriptive
      analysis was performed for both groups, and for comparisons, Mann-Whitney U test
      was used. RESULTS: In terms of VG values, no statistically significant
      differences were observed except for values at 6 and 7 mm apically to the healing
      abutment which favoured the TG. Mean values were 0.69 +/- 0.23 mm for CG while TG
      obtained 0.79 +/- 0.10 mm (p = .64). Regarding Keratinized tissue (KT) width
      statistical significant differences were found favouring TG, which obtained a
      gain of 0.83 +/- 0.61 mm compared with 0.22 +/- 0.48 mm for CG (p = .009). Pink
      esthetic scores resulted in mean values of 10.07 +/- 2.19 for the CG, while TG
      obtained 9.15 +/- 2.34. CONCLUSIONS: Both procedures were effective in increasing
      soft tissue volume with no statistically significant differences. A longer follow
      up is needed to confirm or refute these results.

PMID- 29334404
TI  - Special Issue "Chiroptical Spectroscopy: Instrumentation, Experimental Aspects
      and Applications" in memory of Ettore Castiglioni.

PMID- 29334405
TI  - High-resolution dental magnetic resonance imaging for planning palatal graft
      surgery-a clinical pilot study.
AB  - AIM: To evaluate whether high-resolution, non-contrast-enhanced dental magnetic
      resonance imaging (MRI) can be used for accurate determination of palatal
      masticatory mucosa thickness (PMMT) and to locate the greater palatal artery
      (GPA). MATERIALS AND METHODS: In five volunteers (four males, one female; mean
      age 30.2 +/- 0.4 years), two independent raters measured PMMT by use of dental
      MRI in 180 positions. For comparison, clinical bone sounding was performed. The
      GPA was identified in time-of-flight (TOF) angiography and MSVAT-SPACE-prototype
      sequence. Intra- and inter-observer agreement for MRI measurements, agreement
      between MRI and bone sounding were analysed by intra-class correlation
      coefficient (ICC) and Cohen's kappa (kappa). RESULTS: Reliability of dental MRI
      measurements was high (intra-observer-ICC 0.962; inter-observer ICC 0.959).
      Agreement of MRI measurements with bone sounding was moderate (ICC 0.744), and
      the GPA could be identified in 60% of measurement points using the TOF
      angiography alone and in 85% with additional information of the MSVAT-SPACE. Good
      intra-observer agreement was observed for GPA identification (kappa: 0.778).
      CONCLUSION: Palatal masticatory mucosa thickness measured by high-resolution, non
      contrast enhanced dental MRI is comparable with that obtained by bone sounding.
      Dental MRI enables reliable, non-invasive and radiation-free planning of palatal
      tissue harvesting and can also be used for location of the GPA at 85% of
      measurement points, which might help reduce complications during surgery.

PMID- 29334407
TI  - Chiral separation of novel iminonaringenin derivatives.
AB  - A series of 4-iminonaringenin derivatives 2-6 have been prepared in good overall
      yields from a condensation reaction between naringenin and primary amines. The
      structures of all products were confirmed by ultraviolet, infrared, proton
      nuclear magnetic resonance, and carbon-13 nuclear magnetic resonance
      spectroscopic techniques. These derivatives were analyzed by high-performance
      liquid chromatography using polysaccharide-based chiral stationary phases,
      namely, Chiralpak IB and Chiralcel OD, using various mobile phases. 2-Propanol
      showed a high enantioselectivity for naringin and its derivatives using achiral
      column containing immobilized polysaccharides (Chiralpak IB).

PMID- 29334406
TI  - Dasatinib-induced pulmonary arterial hypertension.
AB  - Drug-induced (group 1) pulmonary hypertension (PH) is an important subgroup of PH
      involving dasatinib as a likely related agent, which is a second-generation
      tyrosine kinase inhibitor (TKI) used in the treatment of chronic myeloid
      leukaemia (CML). The mechanism of dasatinib-induced pulmonary arterial
      hypertension (PAH) is unclear. However, the occurrence of PAH with late onset in
      CML patients suggests a chronic pathological mechanism with an insidious onset
      rather than an acute inflammatory or cardiac aetiology. Dasatinib has a broader
      effect than other TKIs; the major known difference between dasatinib and other
      TKIs is the additional inhibition of Src family kinases. Therefore, Src
      inhibition was thought to play a role in the development of dasatinib-induced
      PAH. However, recently, it was also speculated that chronic dasatinib therapy may
      cause pulmonary endothelial damage, attenuate hypoxic pulmonary vasoconstriction
      responses and increase susceptibility to PAH independently of the Src family
      kinase-induced mechanism. Dasatinib-induced PAH usually seems to be reversible
      with the cessation of the drug, and sometimes with PAH-specific treatment
      strategies. Transthoracic echocardiography can be recommended as a routine
      screening prior to dasatinib initiation, and this non-invasive procedure can be
      utilized in patients having signs and symptoms attributable to PAH during
      dasatinib treatment.

PMID- 29334408
TI  - Effects of metalaxyl enantiomers stress on root activity and leaf antioxidant
      enzyme activities in tobacco seedlings.
AB  - The objective of this experiment was to study the effects of metalaxyl
      enantiomers on the activity of roots and antioxidative enzymes in tobacco
      seedlings. Water culture experiment was conducted to analyze the effects of
      different concentrations of metalaxyl enantiomers (30 and 10 mg L-1 ) on root
      activity and leaf superoxide dismutase (SOD), peroxidase (POD), and catalase
      (CAT) activities and malondialdehyde (MDA) content of tobacco seedlings. The
      results showed that metalaxyl significantly inhibited root activity and
      significantly improved leaf SOD, POD, and CAT activities and MDA content. A
      better physiological response in tobacco seedlings was observed at 30 mg L-1 than
      at 10 mg L-1 metalaxyl. The stereoselectivity for different enantiomers had no
      obvious effect on root activity and the leaf POD activity, but it affected
      significantly the SOD and CAT activities and MDA content. The SOD activity was
      promoted more by R-enantiomer than by S-enantiomer at 30 mg L-1 metalaxyl, and
      the same effect was observed on CAT activity from the beginning to the end of the
      stress period. The MDA content under the stress by R-enantiomer was higher than
      that under the stress by S-enantiomer at 10 mg L-1 metalaxyl.

PMID- 29334409
TI  - Climate-driven mitochondrial selection: A test in Australian songbirds.
AB  - Diversifying selection between populations that inhabit different environments
      can promote lineage divergence within species and ultimately drive speciation.
      The mitochondrial genome (mitogenome) encodes essential proteins of the oxidative
      phosphorylation (OXPHOS) system and can be a strong target for climate-driven
      selection (i.e., associated with inhabiting different climates). We investigated
      whether Pleistocene climate changes drove mitochondrial selection and evolution
      within Australian birds. First, using phylogeographic analyses of the
      mitochondrial ND2 gene for 17 songbird species, we identified mitochondrial
      clades (mitolineages). Second, using distance-based redundancy analyses, we
      tested whether climate predicts variation in intraspecific genetic divergence
      beyond that explained by geographic distances and geographic position. Third, we
      analysed 41 complete mitogenome sequences representing each mitolineage of 17
      species using codon models in a phylogenetic framework and a biochemical approach
      to identify signals of selection on OXPHOS protein-coding genes and test for
      parallel selection in mitolineages of different species existing in similar
      climates. Of 17 species examined, 13 had multiple mitolineages (range: 2-6).
      Climate was a significant predictor of mitochondrial variation in eight species.
      At least two amino acid replacements in OXPHOS complex I could have evolved under
      positive selection in specific mitolineages of two species. Protein homology
      modelling showed one of these to be in the loop region of the ND6 protein channel
      and the other in the functionally critical helix HL region of ND5. These findings
      call for direct tests of the functional and evolutionary significance of
      mitochondrial protein candidates for climate-associated selection.

PMID- 29334410
TI  - Selective Binding and Precipitation of Cesium Ions from Aqueous Solutions: A Size
      Driven Supramolecular Reaction.
AB  - The nuclear disasters of Chernobyl and Fukushima presented an urgent need for
      finding solutions to treatment of radioactive wastes. Among the by-products of
      nuclear fission is radioactive 137 Cs, which evokes an environmental hazard due
      to its long half-life (>30 years) and high solubility in water. In this work, a
      water-soluble organic ligand, readily obtained from alloxan and 1,3,5
      benzenetriol, has been found to selectively bind and precipitate Cs+ ions from
      aqueous solutions. The special rigid structure of the ligand, which consists of a
      "tripodal" carbonyl base above and below an aromatic plane, contributes to the
      size-driven selectivity towards the large Cs+ ions and the formation of a giant,
      insoluble supramolecular complex. In addition to the low costs of the ligand,
      high yields and effectiveness in precipitating Cs+ ions, the Cs-complex revealed
      a high endurance to continuous doses of gamma-radiation, increasing its potential
      to act as a precipitating agent for 137 Cs.

PMID- 29334411
TI  - Nickel-Catalyzed C-S Bond Formation via Decarbonylative Thioetherification of
      Esters, Amides and Intramolecular Recombination Fragment Coupling of Thioesters.
AB  - A nickel catalyzed cross-coupling protocol for the straightforward C-S bond
      formation has been developed. Various mercaptans and a wide range of ester and
      amide substrates bearing various substituents were tolerated in this process
      which afforded products in good to excellent yields. Furthermore, an
      intramolecular protocol for the synthesis of thioethers starting from thioesters
      has been developed. The utility of this protocol has been demonstrated in a new
      synthetic protocol of benzothiophene.

PMID- 29334412
TI  - Stallion semen quality depends on major histocompatibility complex matching to
      teaser mare.
AB  - The major histocompatibility complex (MHC) has repeatedly been found to influence
      mate choice of vertebrates, with MHC-dissimilar mates typically being preferred
      over MHC-similar mates. We used horses (Equus caballus) to test whether MHC
      matching also affects male investment into ejaculates after short exposure to a
      female. Semen characteristics varied much among stallions. Controlling for this
      variance with a full-factorial within-subject experimental design, we found that
      a short exposure to an MHC-dissimilar mare enhanced male plasma testosterone and
      led to ejaculates with elevated sperm numbers as compared to exposure to an MHC
      similar mare. Sperm velocity seemed not affected by the treatment. Overall
      genetic similarity between stallions and mares (determined from polymorphic
      microsatellites on 20 different chromosomes) played no significant role here. The
      MHC type of the teaser mare also affected characteristics of cold-stored sperm
      after 24 and 48 hr. As expected from ejaculate economics, sperm viability was
      elevated after exposure to an MHC-dissimilar mare. However, oxidative stress and
      the percentage of sperm with a high DNA fragmentation were mostly increased after
      exposure to an MHC-dissimilar mare, depending also on whether the teaser mare was
      in oestrous or not. We conclude that males can quickly adjust ejaculate quality
      relative to a female's MHC, and that this male reaction to the social environment
      can also affect important characteristics of cold-stored semen.

PMID- 29334413
TI  - Features of Auxiliaries That Enable Native Chemical Ligation beyond Glycine and
      Cleavage via Radical Fragmentation.
AB  - Native chemical ligation (NCL) is an invaluable tool in the total chemical
      synthesis of proteins. Ligation auxiliaries overcome the requirement for
      cysteine. However, the reported auxiliaries remained limited to glycine
      containing ligation sites and the acidic conditions applied for cleavage of the
      typically applied N-benzyl-type linkages promote side reactions. With the aim to
      improve upon both ligation and cleavage, we systematically investigated
      alternative ligation scaffolds that challenge the N-benzyl dogma. The study
      revealed that auxiliary-mediated peptide couplings are fastest when the ligation
      proceeds via 5-membered rather than 6-membered rings. Substituents in alpha
      position of the amine shall be avoided. We observed, perhaps surprisingly, that
      additional beta-substituents accelerated the ligation conferred by the beta
      mercaptoethyl scaffold. We also describe a potentially general means to remove
      ligation auxiliaries by treatment with an aqueous solution of
      triscarboxyethylphosphine (TCEP) and morpholine at pH 8.5. NMR analysis of a 13 C
      labeled auxiliary showed that cleavage most likely proceeds through a radical
      triggered oxidative fragmentation. High ligation rates provided by beta
      substituted 2-mercaptoethyl scaffolds, their facile introduction as well as the
      mildness of the cleavage reaction are attractive features for protein synthesis
      beyond cysteine and glycine ligation sites.

PMID- 29334414
TI  - Cryptic species as a window into the paradigm shift of the species concept.
AB  - The species concept is the cornerstone of biodiversity science, and any paradigm
      shift in the delimitation of species affects many research fields. Many
      biologists now are embracing a new "species" paradigm as separately evolving
      populations using different delimitation criteria. Individual criteria can emerge
      during different periods of speciation; some may never evolve. As such, a
      paradigm shift in the species concept relates to this inherent heterogeneity in
      the speciation process and species category-which is fundamentally overlooked in
      biodiversity research. Cryptic species fall within this paradigm shift: they are
      continuously being reported from diverse animal phyla but are poorly considered
      in current tests of ecological and evolutionary theory. The aim of this review is
      to integrate cryptic species in biodiversity science. In the first section, we
      address that the absence of morphological diversification is an evolutionary
      phenomenon, a "process" counterpart to the long-studied mechanisms of
      morphological diversification. In the next section regarding taxonomy, we show
      that molecular delimitation of cryptic species is heavily biased towards distance
      based methods. We also stress the importance of formally naming of cryptic
      species for better integration into research fields that use species as units of
      analysis. Finally, we show that incorporating cryptic species leads to novel
      insights regarding biodiversity patterns and processes, including large-scale
      biodiversity assessments, geographic variation in species distribution and
      species coexistence. It is time for incorporating multicriteria species
      approaches aiming to understand speciation across space and taxa, thus allowing
      integration into biodiversity conservation while accommodating for species
      uncertainty.

PMID- 29334415
TI  - Early burst in body size evolution is uncoupled from species diversification in
      diving beetles (Dytiscidae).
AB  - Changes in morphology are often thought to be linked to changes in species
      diversification, which is expected to leave a signal of early burst (EB) in
      phenotypic traits. However, such signal is rarely recovered in empirical
      phylogenies, even for groups with well-known adaptive radiation. Using a
      comprehensive phylogenetic approach in Dytiscidae, which harbours ~4,300 species
      with as much as 50-fold variation in body size among them, we ask whether pattern
      of species diversification correlates with morphological evolution. Additionally,
      we test whether the large variation in body size is linked to habitat preference
      and whether the latter influences species turnover. We found, in sharp contrast
      to most animal groups, that Dytiscidae body size evolution follows an early-burst
      model with subsequent high phylogenetic conservatism. However, we found no
      evidence for associated shifts in species diversification, which point to an
      uncoupled evolution of morphology and species diversification. We recovered the
      ancestral habitat of Dytiscidae as lentic (standing water), with many transitions
      to lotic habitat (running water) that are concomitant to a decrease in body size.
      Finally, we found no evidence for difference in net diversification rates between
      habitats nor difference in turnover in lentic and lotic species. This result,
      together with recent findings in dragonflies, contrasts with some theoretical
      expectations of the habitat stability hypothesis. Thus, a thorough reassessment
      of the impact of dispersal, gene flow and range size on the speciation process is
      needed to fully encompass the evolutionary consequences of the lentic-lotic
      divide for freshwater fauna.

PMID- 29334416
TI  - Investigating causal associations between use of nicotine, alcohol, caffeine and
      cannabis: a two-sample bidirectional Mendelian randomization study.
AB  - BACKGROUND AND AIMS: Epidemiological studies consistently show co-occurrence of
      use of different addictive substances. Whether these associations are causal or
      due to overlapping underlying influences remains an important question in
      addiction research. Methodological advances have made it possible to use
      published genetic associations to infer causal relationships between phenotypes.
      In this exploratory study, we used Mendelian randomization (MR) to examine the
      causality of well-established associations between nicotine, alcohol, caffeine
      and cannabis use. METHODS: Two-sample MR was employed to estimate bidirectional
      causal effects between four addictive substances: nicotine (smoking initiation
      and cigarettes smoked per day), caffeine (cups of coffee per day), alcohol (units
      per week) and cannabis (initiation). Based on existing genome-wide association
      results we selected genetic variants associated with the exposure measure as an
      instrument to estimate causal effects. Where possible we applied sensitivity
      analyses (MR-Egger and weighted median) more robust to horizontal pleiotropy.
      RESULTS: Most MR tests did not reveal causal associations. There was some weak
      evidence for a causal positive effect of genetically instrumented alcohol use on
      smoking initiation and of cigarettes per day on caffeine use, but these were not
      supported by the sensitivity analyses. There was also some suggestive evidence
      for a positive effect of alcohol use on caffeine use (only with MR-Egger) and
      smoking initiation on cannabis initiation (only with weighted median). None of
      the suggestive causal associations survived corrections for multiple testing.
      CONCLUSIONS: Two-sample Mendelian randomization analyses found little evidence
      for causal relationships between nicotine, alcohol, caffeine and cannabis use.

PMID- 29334417
TI  - Combining allele frequency and tree-based approaches improves phylogeographic
      inference from natural history collections.
AB  - Model selection approaches in phylogeography have allowed researchers to evaluate
      the support for competing demographic histories, which provides a mode of
      inference and a measure of uncertainty in understanding climatic and spatial
      influences on intraspecific diversity. Here, to rank all models in the comparison
      set and determine what proportion of the total support the top-ranked model
      garners, we conduct model selection using two analytical approaches-allele
      frequency-based, implemented in fastsimcoal2, and gene tree-based, implemented in
      phrapl. We then expand this model selection framework by including an assessment
      of absolute fit of the models to the data. For this, we utilize DNA isolated from
      existing natural history collections that span the distribution of red alder
      (Alnus rubra) in the Pacific Northwest of North America to generate genomic data
      for the evaluation of 13 demographic scenarios. The quality of DNA recovered from
      herbarium specimen leaf tissue was assessed for its utility and effectiveness in
      demographic model selection, specifically in the two approaches mentioned. We
      present strong support for the use of herbarium tissue in the generation of
      genomic DNA, albeit with the inclusion of additional quality control checks prior
      to library preparation and analyses with multiple approaches that incorporate
      various data. Analyses with allele frequency spectra and gene trees predominantly
      support A. rubra having experienced an ancient vicariance event with intermittent
      and frequent gene flow between the disjunct populations. Additionally, the data
      consistently fit the most frequently selected model, corroborating the model
      selection techniques. Finally, these results suggest that the A. rubra disjunct
      populations do not represent separate species.

PMID- 29334418
TI  - Antimicrobial and stress responses to increased temperature and bacterial
      pathogen challenge in the holobiont of a reef-building coral.
AB  - Global increases in coral disease prevalence have been linked to ocean warming
      through changes in coral-associated bacterial communities, pathogen virulence and
      immune system function. However, the interactive effects of temperature and
      pathogens on the coral holobiont are poorly understood. Here, we assessed three
      compartments of the holobiont (host, Symbiodinium and bacterial community) of the
      coral Montipora aequituberculata challenged with the pathogen Vibrio
      coralliilyticus and the commensal bacterium Oceanospirillales sp. under ambient
      (27 degrees C) and elevated (29.5 and 32 degrees C) seawater temperatures. Few
      visual signs of bleaching and disease development were apparent in any of the
      treatments, but responses were detected in the holobiont compartments. V.
      coralliilyticus acted synergistically and negatively impacted the photochemical
      efficiency of Symbiodinium at 32 degrees C, while Oceanospirillales had no
      significant effect on photosynthetic efficiency. The coral, however, exhibited a
      minor response to the bacterial challenges, with the response towards V.
      coralliilyticus being significantly more pronounced, and involving the
      prophenoloxidase-activating system and multiple immune system-related genes.
      Elevated seawater temperatures did not induce shifts in the coral-associated
      bacterial community, but caused significant gene expression modulation in both
      Symbiodinium and the coral host. While Symbiodinium exhibited an antiviral
      response and upregulated stress response genes, M. aequituberculata showed
      regulation of genes involved in stress and innate immune response processes,
      including immune and cytokine receptor signalling, the complement system, immune
      cell activation and phagocytosis, as well as molecular chaperones. These
      observations show that M. aequituberculata is capable of maintaining a stable
      bacterial community under elevated seawater temperatures and thereby contributes
      to preventing disease development.

PMID- 29334419
TI  - A Metallo Pro-Drug to Target CuII in the Context of Alzheimer's Disease.
AB  - Alzheimer's disease and oxidative stress are connected. In the present
      communication, we report the use of a MnII -based superoxide dismutase (SOD)
      mimic ([MnII (L)]+ , 1+ ) as a pro-drug candidate to target CuII -associated
      events, namely, CuII -induced formation of reactive oxygen species (ROS) and
      modulation of the amyloid-beta (Abeta) peptide aggregation. Complex 1+ is able to
      remove CuII from Abeta, stop ROS and prevent alteration of Abeta aggregation as
      would do the corresponding free ligand LH. Using 1+ instead of LH in further
      biological applications would have the double advantage to avoid the cell
      toxicity of LH and to benefit from its proved SOD-like activity.

PMID- 29334420
TI  - Copper-Catalyzed Regioselective Cleavage of C-X and C-H Bonds: A Strategy for
      Sulfur Dioxide Fixation.
AB  - The first example of direct fixation of sulfur dioxide between heteroaryls and
      aryl halides has been developed via copper-catalyzed regioselective cleavage of C
      X and C-H bonds under base-free and ligand-free conditions by using DABSO (1,4
      diazabicyclo[2.2.2]octane bis(sulfur dioxide)) as a solid and bench-stable sulfur
      dioxide surrogate. This mild protocol results in double C-S bond-forming
      reactions from simple precursors in the absence of prefunctionalized
      organometallic reagents, arenediazonium salts, and iodonium salts which extends
      the still limited number of sulfur dioxide fixation strategies.

PMID- 29334421
TI  - A Survey of tooth morphology teaching methods employed in the United Kingdom and
      Ireland.
AB  - BACKGROUND: Tooth morphology is a central component of the dental curriculum and
      is applicable to all dental specialities. Traditional teaching methods are being
      supplemented with innovative strategies to tailor teaching and accommodate the
      learning styles of the recent generation of students. METHODS: An online survey
      was compiled and distributed to the staff involved in teaching tooth morphology
      in the United Kingdom and Ireland to assess the importance of tooth morphology in
      the dentistry curriculum and the methodologies employed in teaching. RESULTS: The
      results of the survey show that tooth morphology constitutes a small module in
      the dental curriculum. It is taught in the first 2 years of the dental curriculum
      but is applicable in the clinical years and throughout the dental career.
      Traditional teaching methods, lecture and practical, are being augmented with
      innovative teaching including e-learning via virtual learning environment, tooth
      atlas and e-books leading to blended learning. The majority of the schools teach
      both normal dental anatomy and morphologic variations of dental anatomy and
      utilise plastic teeth for practical and examination purposes. Learning the 3D
      aspects of tooth morphology was deemed important by most of the respondents who
      also agreed that tooth morphology is a difficult topic for the students.
      CONCLUSION: Despite being core to the dental curriculum, overall minimal time is
      dedicated to the delivery of tooth morphology, creating a reliance on the student
      to learn the material. New forms of delivery including computer-assisted learning
      tools should help sustain learning and previously acquired knowledge.

PMID- 29334422
TI  - Psychosocial risks at the workplace and quality of life in cancer survivors in
      employment.

PMID- 29334423
TI  - Mechanochemical Activation of Iron Cyano Complexes: A Prebiotic Impact Scenario
      for the Synthesis of alpha-Amino Acid Derivatives.
AB  - Mechanochemical activation of iron cyano complexes by ball milling results in the
      formation of HCN, which can be trapped and incorporated into alpha-aminonitriles.
      This prebiotic impact scenario can be extended by mechanochemically transforming
      the resulting alpha-aminonitriles into alpha-amino amides using a chemical route
      related to early Earth conditions.

PMID- 29334424
TI  - In Vivo EPR Characterization of Semi-Synthetic [FeFe] Hydrogenases.
AB  - EPR spectroscopy reveals the formation of two different semi-synthetic
      hydrogenases in vivo. [FeFe] hydrogenases are metalloenzymes that catalyze the
      interconversion of molecular hydrogen and protons. The reaction is catalyzed by
      the H-cluster, consisting of a canonical iron-sulfur cluster and an
      organometallic [2Fe] subsite. It was recently shown that the enzyme can be
      reconstituted with synthetic cofactors mimicking the composition of the [2Fe]
      subsite, resulting in semi-synthetic hydrogenases. Herein, we employ EPR
      spectroscopy to monitor the formation of two such semi-synthetic enzymes in whole
      cells. The study provides the first spectroscopic characterization of semi
      synthetic hydrogenases in vivo, and the observation of two different oxidized
      states of the H-cluster under intracellular conditions. Moreover, these findings
      underscore how synthetic chemistry can be a powerful tool for manipulation and
      examination of the hydrogenase enzyme under in vivo conditions.

PMID- 29334426
TI  - Current Resources for Evidence-Based Practice, January/February 2018.

PMID- 29334425
TI  - Updates From the Literature, January/February 2018.

PMID- 29334427
TI  - Management of Labor: Are the New Guidelines Justified?

PMID- 29334428
TI  - Development of Potent Inhibitors of the Mycobacterium tuberculosis Virulence
      Factor Zmp1 and Evaluation of Their Effect on Mycobacterial Survival inside
      Macrophages.
AB  - The enzyme Zmp1 is a zinc-containing peptidase that plays a critical role in the
      pathogenicity of Mycobacterium tuberculosis. Herein we describe the
      identification of a small set of Zmp1 inhibitors based on a novel 8
      hydroxyquinoline-2-hydroxamate scaffold. Among the synthesized compounds, N
      (benzyloxy)-8-hydroxyquinoline-2-carboxamide (1 c) was found to be the most
      potent Zmp1 inhibitor known to date, and its binding mode was analyzed both by
      kinetics studies and molecular modeling, identifying critical interactions of 1 c
      with the zinc ion and residues in the active site. The effect of 1 c on
      intracellular Mycobacterium survival was assayed in J774 murine macrophages
      infected with M. tuberculosis H37Rv or M. bovis BCG and human monocyte-derived
      macrophages infected with M. tuberculosis H37Rv. Cytotoxicity and genotoxicity
      were also assessed. Overall, inhibitor 1 c displays interesting in vitro
      antitubercular properties worthy of further investigation.

PMID- 29334429
TI  - Superhydrophobic/Superhydrophilic Janus Fabrics Reducing Blood Loss.
AB  - Hemostatic fabrics are most commonly used in baseline emergency treatment;
      however, the unnecessary blood loss due to the excessive blood absorption by
      traditional superhydrophilic fabrics is overlooked. Herein, for the first time,
      superhydrophobic/superhydrophilic Janus fabrics (superhydrophobic on one side and
      superhydrophilic on the other) are proposed: the superhydrophilic part absorbs
      water in the blood to expedite the clotting while the superhydrophobic part
      prevents blood from further permeating. Compared with the common counterparts,
      effective bleeding control with reducing blood loss more than 50% can be achieved
      while the breathability largely remain by using Janus fabrics. The proposed
      prototypes can even prolong the survival time in the rat model with serious
      bleeding. This strategy for reducing blood loss via simply tuning wettability is
      promising for the practical applications.

PMID- 29334430
TI  - Preclinical therapeutic efficacy of the ciprofloxacin-eluting sinus stent for
      Pseudomonas aeruginosa sinusitis.
AB  - BACKGROUND: The ciprofloxacin-coated sinus stent (CSS) has unique therapeutic
      potential to deliver antibiotics to the sinuses. The objective of this study is
      to evaluate the efficacy of the CSS stent in eliminating Pseudomonas aeruginosa
      infection in a rabbit model of sinusitis. METHODS: A ciprofloxacin-eluting sinus
      stent was created by coating ciprofloxacin/Eudragit RS100 on biodegradable poly
      D/L-lactic acid (2 mg). After analyzing in-vitro inhibition of P aeruginosa (PAO
      1 strain) biofilm formation, a total of 8 stents (4 shams, 4 CSSs) were placed
      unilaterally in rabbit maxillary sinuses via dorsal sinusotomy after inducing
      infection for 1 week with PAO-1. Animals were assessed 2 weeks after stent
      insertion with nasal endoscopy, sinus culture, computed tomography (CT) scan,
      histopathology, and scanning electron microscopy (SEM). RESULTS: PAO-1 biofilm
      formation was significantly reduced in vitro with exposure to the CSS (p <
      0.0001). Insertion of the stent in PAO-1-infected rabbits for 2 weeks resulted in
      significant improvement in sinusitis according to endoscopy scoring (p < 0.0001)
      and CT scoring (p < 0.002). Histology and SEM revealed marked improvement in the
      structure of the mucosa and submucosa with no detection of biofilm structures in
      the CSS cohort. CONCLUSION: Although this study had a small sample size, we
      identified robust therapeutic efficacy of the CSS by reducing bacterial load and
      biofilm formation of P aeruginosa in a preclinical model of sinusitis after
      placement for 2 weeks.

PMID- 29334431
TI  - Activation state of circulating eosinophils in nasal polyposis.
AB  - BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common disease
      with an uncertain pathophysiology. It is characterized by polyps rich in
      eosinophils, with an activation status already investigated at the tissue level.
      In a group of CRSwNP patients, we assessed the activation status of circulating
      eosinophils in the blood before migration into tissues. METHODS: Thirteen
      patients with CRSwNP and 16 healthy volunteers were enrolled. Several biologic
      parameters were studied: blood count of eosinophils; plasma eosinophil cationic
      protein; oxidative metabolism by chemiluminescence at baseline or when activated
      by phorbol 12-myristate 13-acetate or platelet-activating factor, with or without
      interleukin-5 (IL-5); percent of granulosar cells; and mean fluorescence
      intensity (MFI) by flow cytometry. RESULTS: The mean number of eosinophils was
      significantly higher in patients with CRSwNP, whose eosinophils showed increased
      oxidative metabolism in the basal or activated state significantly decreasing in
      the presence of IL-5. There was also a higher percentage of CD49d+ , CD25+ , and
      CCR3+ cells in patients, and a nonsignificant decrease in descending order in MFI
      between the control group, patients with normal eosinophil levels, patients with
      hypereosinophilia, and patients with aspirin-exacerbated respiratory disease.
      CONCLUSION: This study demonstrates a priming state of circulating eosinophils in
      CRSwNP patients when compared with healthy controls, as evidenced by the extent
      of oxidative metabolism, with increased sensitivity to IL-5 and by the observed
      variations of percent and MFI of CD49d, CCR3, and CD25. This priming is thus
      found at the peripheral level and occurs before the migration of eosinophils to
      polyps, reflecting the systemic and not just local nature of abnormalities in
      CRSwNP.

PMID- 29334432
TI  - Antibiotic use patterns in endoscopic sinus surgery: a survey of the American
      Rhinologic Society membership.
AB  - BACKGROUND: There is a paucity of data supporting antibiotic use in endoscopic
      sinus surgery (ESS). The objective of this study is to determine perioperative
      antibiotic use patterns and factors which influence use in ESS. METHODS: An
      online-based survey was distributed to members of the American Rhinologic Society
      (ARS). Outcomes included timing of perioperative antibiotic use, practice
      environment, years of experience, and patient factors that influenced antibiotic
      use. RESULTS: There were 204 responses (response rate 18.3%); 36.8% of
      respondents were in academic positions, 32.8% were in private practice, and 30.4%
      were in academic-affiliated private practice; 20.6% routinely gave preoperative
      antibiotics, most commonly to reduce bacterial burden (59.5%) and mucosal
      inflammation (59.5%); 54.4% routinely gave intraoperative antibiotics, most
      commonly to reduce the risk of postoperative infection (63.1%); 62.3% routinely
      gave postoperative antibiotics, citing the need to reduce the risk of
      postoperative infection (75.6%). Diagnosis influenced postoperative antibiotic
      use in 63.0%. Preoperative antibiotics were more likely to be prescribed by
      respondents with more than 5 years of experience (odds ratio [OR] 2.97; 95%
      confidence interval [CI], 1.04 to 8.54; p = 0.043). Compared to private
      practitioners, academicians were more likely to give intraoperative antibiotics
      (OR 2.68; 95% CI, 1.39 to 5.17; p = 0.003), but not preoperative or postoperative
      antibiotics. Use of nonabsorbable packing was significantly associated with use
      of postoperative antibiotics (OR 2.01; 95% CI, 1.07 to 3.77; p = 0.031).
      CONCLUSION: This study demonstrates the significant variation in perioperative
      antibiotic use among otolaryngologists. These results provide support for the
      establishment of evidence-based practice guidelines for perioperative antibiotic
      use in ESS.

PMID- 29334433
TI  - Happy Birthday Karel!

PMID- 29334434
TI  - The Case for Stabilized Stannous Fluoride Dentifrice: An Advanced Formulation
      Designed for Patient Preference.
AB  - Oral diseases, particularly caries and gingivitis, continue to be widespread.
      Incorporating a stabilized stannous fluoride dentifrice into patients' daily oral
      hygiene routine is a convenient, cost effective approach to improve and protect
      their oral health and the appearance of their smile. Unlike other common
      fluorides that only provide anti-caries benefits (e.g., sodium fluoride and
      sodium monofluorophosphate), stabilized stannous fluoride formulations have
      demonstrated broader and significantly greater protection, also reducing plaque,
      gingivitis, erosion, sensitivity, and halitosis. To deliver the full range of
      benefits and simultaneously deliver whitening and tartar control benefits,
      stannous fluoride requires careful formulation. Procter & Gamble is the only
      dentifrice manufacturer with decades of patented innovations to overcome these
      formulation challenges, resulting in a large portfolio of stannous fluoride
      containing dentifrice products marketed under the Crest(r) Pro-HealthTM name that
      are available today. The most recent innovation is a "smooth texture" variant of
      Crest Pro-Health, containing stabilized stannous fluoride with zinc citrate as
      the anti-calculus agent. This product was developed to deliver a patient
      preferred brushing experience with the full range of benefits offered by Crest
      Pro-Health. This article discusses two common misconceptions about dentifrice,
      describes the history of key Crest stannous fluoride innovations, and outlines
      the research in this issue demonstrating health and cosmetic benefits of the new
      Crest Pro-Health smooth texture variant.

PMID- 29334435
TI  - Comparative Antiplaque Effect of Two Antimicrobial Dentifrices: Laboratory and
      Clinical Evaluations.
AB  - OBJECTIVES: To compare the effect of a stannous fluoride dentifrice versus a
      triclosan-containing dentifrice on the reduction of plaque using in vitro and
      clinical models. METHODS: Both investigations evaluated a novel 0.454% stabilized
      stannous fluoride dentifrice (Crest(r) Pro-HealthTM smooth formula) versus a
      sodium fluoride/triclosan positive control dentifrice (Colgate(r) Total(r)). The
      in vitro evaluation utilized the Plaque Glycolysis and Regrowth Model (PGRM),
      wherein the metabolic effects (acid production/glycolysis inhibition) of the
      dentifrices were assessed on plaque biofilms grown on glass rods after three days
      growth and a single dentifrice treatment. Treatments were evaluated via analysis
      of variance, Student's t-test. The clinical trial was a four-week, single-center,
      randomized and controlled, double-blind, parallel group study, where 120 adults
      were randomized to one of the two dentifrices for use at home according to
      manufacturer's instructions. Plaque was evaluated at baseline and Week 4 with the
      Rustogi Modified Navy Plaque Index (RMNPI). Statistical analyses were via
      analysis of covariance. RESULTS: In vitro PGRM: The stannous fluoride dentifrice
      provided 43.3% glycolysis inhibition compared to 27.5% for the triclosan control,
      and the pH decrease associated with acid production was significantly less for
      stannous fluoride (0.87) versus triclosan (1.11); p < 0.05. Clinical trial: One
      hundred eighteen (118) subjects completed the study with fully evaluable data.
      Both dentifrice groups demonstrated statistically significant (p < 0.0001)
      reductions in plaque at Week 4 compared with baseline, with the stannous fluoride
      dentifrice producing a significantly lower adjusted mean Week 4 plaque score (p <
      0.0001) versus the triclosan positive control for whole mouth plaque (23.1%
      lower) and interproximal plaque (43.5% lower). Both dentifrices were well
      tolerated. CONCLUSIONS: The stabilized stannous fluoride dentifrice provided
      statistically significant reductions in plaque glycolysis in vitro and plaque
      growth in vivo compared to the triclosan dentifrice. Results for both studies
      were consistent.

PMID- 29334436
TI  - Assessment of the Effects of a Novel Stabilized Stannous Fluoride Dentifrice on
      Gingivitis in a Two-Month Positive-Controlled Clinical Study.
AB  - OBJECTIVES: The aim of this study was to compare the antibleeding/antigingivitis
      effectiveness of a newly formulated 0.454% stabilized stannous fluoride
      dentifrice and a marketed positive control triclosan-containing dentifrice in
      adults with mild-to-moderate gingivitis. METHODS: This single-center, two-month,
      randomized and controlled, double-blind, parallel group clinical trial involved
      adults with preexisting mild-to-moderate gingivitis. Baseline bleeding and
      gingivitis levels were assessed with the Gingival Bleeding Index (GBI) and Lobene
      Modified Gingival Index (MGI). Subjects were randomly assigned to either a new
      smooth formula 0.454% stabilized stannous fluoride test dentifrice (Crest(r) Pro
      HealthTM) or a commercially available positive control 0.30% triclosan dentifrice
      (Colgate(r) Total(r)). Subjects brushed with their assigned dentifrice at home
      according to the manufacturer's instructions. At Month 2, subjects were re
      evaluated for bleeding and gingivitis as at Baseline, with MGI and GBI
      evaluations. RESULTS: Of the 200 subjects randomized to treatment, 197 completed
      the study and had fully evaluable data. At Month 2, both the stannous fluoride
      and triclosan control dentifrices produced statistically significant reductions
      (p < 0.0001) in the mean number of bleeding sites, MGI, and GBI compared to
      Baseline. Use of this 0.454% stannous fluoride dentifrice resulted in 22% fewer
      bleeding sites versus the positive control triclosan dentifrice (p < 0.0001).
      Similarly, after two months of brushing, the stannous fluoride dentifrice group
      showed statistically significant lower mean MGI and GBI scores than subjects
      using the triclosan positive control dentifrice (p < 0.0001). Both dentifrices
      were well-tolerated. CONCLUSIONS: Subjects brushing with a newly formulated
      stannous fluoride dentifrice had statistically significantly fewer bleeding sites
      and less gingivitis than those using a positive control triclosan dentifrice
      after two months.

PMID- 29334437
TI  - A Randomized Clinical Trial to Measure the Erosion Protection Benefits of a Novel
      Stabilized Stannous Fluoride Dentifrice versus a Control Dentifrice.
AB  - OBJECTIVES: The aim of this investigation was to assess the erosion protection
      ability of a novel stabilized stannous fluoride (SnF2) dentifrice and a control
      sodium fluoride dentifrice (NaF) using a well-credentialed human in situ model.
      METHODS: A novel smooth texture 0.454% stabilized SnF2 dentifrice (Crest(r) Pro
      HealthTM smooth formula) and a 0.23% NaF marketed control dentifrice with 5%
      potassium nitrate (Sensodyne(r) Pronamel(r)) were compared in a 10-day, single
      center, randomized, controlled, double-blind, two-treatment, three-period
      crossover in situ clinical trial. Subjects wore a mandibular buccal appliance
      fitted with eight enamel specimens for approximately six hours over the course of
      each study day. Twice daily, subjects brushed the lingual surfaces of their teeth
      for 30 seconds while wearing the appliance, then swished with their assigned
      treatment toothpaste slurry for 90 seconds under the supervision of clinic staff.
      Erosive acid challenges with a citric acid-containing beverage (commercial orange
      juice) were done four times each day. RESULTS: The SnF2 dentifrice provided 26.9%
      greater erosion protection relative to the NaF dentifrice at Day 10 (p < 0.03).
      Adjusted means of enamel surface loss at Day 10 were 9.117 um for the SnF2
      dentifrice and 12.471 um for the NaF marketed control. CONCLUSIONS: These results
      demonstrate the stabilized SnF2 dentifrice offered greater protection over the
      NaF dentifrice against the initiation and progression of dental erosion.

PMID- 29334438
TI  - In Vitro and In Vivo Evaluations of the Anticalculus Effect of a Novel Stabilized
      Stannous Fluoride Dentifrice.
AB  - OBJECTIVES: To evaluate the effect of a novel stannous fluoride dentifrice with
      zinc citrate on calculus inhibition using both in vitro and clinical models.
      METHODS: Each investigation tested a novel stabilized 0.454% stannous fluoride
      dentifrice with zinc citrate as an anticalculus agent (Crest(r) Pro-HealthTM
      smooth formula) compared to a negative control fluoride dentifrice. The in vitro
      study used the modified Plaque Growth and Mineralization Model (mPGM). Plaque
      biofilms were prepared and mineralized by alternate immersion of glass rods in
      human saliva and artificial mineralization solution. Treatments of 25% w/w
      dentifrice/water slurries were carried out for 60 seconds daily for 6 days,
      between saliva and mineralization solution immersions. Plaque calcium levels were
      determined by digestion and inductively coupled plasma optical emission
      spectroscopy. Student's t-test (p < 0.05) was used for statistical analysis. The
      clinical study was a parallel group, double-blind, randomized, and controlled
      trial. Following a dental prophylaxis, subjects entered a two-month run-in phase.
      At the end, they received a Volpe-Manhold Index (V-MI) calculus examination.
      Eighty (80) qualified subjects who had formed at least 9 mm of calculus on the
      linguals of the mandibular anterior teeth were re-prophied and randomly assigned
      to either the stannous fluoride dentifrice or the negative control. Subjects
      brushed twice daily, unsupervised, during the three-month test period, returning
      at Weeks 6 and 12 for safety and V-MI examinations. Statistical analyses were via
      ANCOVA. RESULTS: In vitro mPGM: The stabilized stannous fluoride dentifrice
      showed 20% less in vitro tartar formation, measured as calcium accumulation
      normalized by biofilm mass, versus the negative control (106.95 versus 133.04 ug
      Ca/mg biofilm, respectively, p < 0.05). Clinical Trial: Seventy-eight (78)
      subjects completed with fully evaluable data. The stannous fluoride dentifrice
      group had 15.1% less adjusted mean calculus at Week 6 compared to the negative
      control group (p = 0.05) and 21.7% less calculus at Week 12 (p < 0.01). Both
      dentifrices were well-tolerated. CONCLUSIONS: The stannous fluoride dentifrice
      produced significant anticalculus benefits in vitro and in a clinical trial
      compared to a negative control.

PMID- 29334439
TI  - Pharmacogenetics - The Year in Review.

PMID- 29334440
TI  - Multifactorial Splenomegaly.
AB  - Splenomegaly is an unusual finding among North Americans, but is commonly seen in
      many parts of the world. Increasingly, it can be encountered locally among recent
      immigrant and refugee populations. A broad differential diagnosis is required. We
      report the case of a 33-year-old refugee with multiple potential causes for
      splenomegaly. Empiric treatment of one of the infectious contributors to his
      splenomegaly resulted in a significant improvement of his quality of life,
      illustrating the importance of a thorough evaluation of potential causes of
      splenomegaly, especially in refugee and immigrant populations.

PMID- 29334441
TI  - Statin Pharmacogenetics: Moving from Toxicity to Efficacy.

PMID- 29334443
TI  - The Sanford School of Medicine's Healthcare Quality Improvement Program:
      Connecting Education with Quality Improvement.

PMID- 29334442
TI  - A Rare Initial Presentation of Primary Diffuse Leptomeningeal PNET in a 10-Year
      Old-Male.
AB  - Primary leptomeningeal primitive neuroectodermal tumors (PNETs) are extremely
      rare childhood central nervous system malignancies harboring a very poor
      prognosis. There is no consensus treatment for these tumors to date. We report a
      case of a 10-year-old male who presented with mental status change,
      hydrocephalus, intracranial and spinal diffuse leptomeningeal enhancement without
      a primary mass upon cranial imaging and a negative initial biopsy until five
      months into his presentation. He responded significantly well to initial
      chemotherapy and radiotherapy.

PMID- 29334444
TI  - Pregnancy and Parenthood During Medical School.
AB  - PURPOSE: The stress of pregnancy and parenthood during the intense educational
      experience of medical school could increase the risk of student burnout. Because
      9.2 percent of U.S. medical students are parents by graduation, it would seem
      prudent to include this topic in wellness programs and policies. The purpose of
      this study was to determine the effects of pregnancy and parenthood on medical
      students. METHOD: This was a cross-sectional, internet survey distributed to all
      four classes of medical students at the University of South Dakota Sanford School
      of Medicine during the 2016-2017 academic year. The survey determined self
      reported pregnancy and parenthood information, knowledge of a medical school
      pregnancy policy, and policy recommendations. RESULTS: More than 85 percent of
      the 194 respondents recommended that the following elements be included in an
      institutional policy: process for arranging parental leave, how leave time might
      affect graduation, how missed requirements could be made up, and how to request
      special accommodation or leave. Twenty-nine of the respondents (15 percent) were
      parents or currently pregnant. Eight pregnancies during medical school were
      associated with complications, including three miscarriages. Of the 18 students
      who reported maternity or paternity leave, 13 (72 percent) and 10 (56 percent)
      would have extended their leave time if it did not delay graduation or only
      reduced their number of elective rotations, respectively. No student would choose
      to extend leave if it would delay graduation. CONCLUSIONS: This survey is the
      first of its kind investigating pregnancy and parenthood in medical students
      attending a U.S. medical school. Students want schools to provide clear, well
      defined guidelines, scheduling flexibility and administrators who are
      approachable and understanding of their individual circumstances.

PMID- 29334445
TI  - The Father of the Problem Oriented Medical Record.

PMID- 29334446
TI  - Pediatric Community Acquired Pneumonia.
AB  - Pediatric community acquired pneumonia (CAP) is frequently encountered by medical
      providers and is one of the most common reasons for hospital admission. CAP is
      known to cause significant morbidity and mortality, causing greater than 2
      million deaths annually worldwide in children younger than five years old. The
      Infectious Disease Society of America (IDSA) released guidelines in 2011 with
      recommendations regarding appropriate diagnosis and management of community
      acquired pneumonia for children greater than 3 months age, with the goal of
      assisting providers in clinical decision making. The guidelines do not recommend
      routine diagnostic work up for previously healthy, appropriately immunized
      patients presenting with mild CAP and are otherwise candidates for outpatient
      treatment. Diagnostic work up indicated for patients presenting with moderate to
      severe disease include CBC with differential, blood culture, acute phase
      reactants and chest radiography. Providers may also consider testing for
      influenza, mycoplasma pneumoniae, and other viral respiratory pathogens depending
      on the patient's presentation. Antibiotics are not routinely recommended, as the
      majority of cases are caused by viral pathogens. Narrow spectrum antibiotics are
      indicated for empiric treatment of bacterial CAP in fully immunized pediatric
      patients who are not penicillin allergic. Despite these new recommendations,
      there continues to be delay in changing the methods of practice in some hospitals
      and clinics. It is important that providers are familiar with the most current
      guidelines to minimize unnecessary laboratory testing and imaging in the
      outpatient setting for mild cases, and to use evidence based recommendations for
      laboratory work up, imaging, and treatment in the inpatient setting.

PMID- 29334447
TI  - The Heart of the Matter: Antidiabetic Medication Effects on Cardiovascular
      Outcomes.

PMID- 29334448
TI  - Quality Focus: Expanding Quality Improvement to Achieve Positive Health Outcomes.

PMID- 29334454
TI  - Aurophilic Interactions in [(L)AuCl]...[(L')AuCl] Dimers: Calibration by
      Experiment and Theory.
AB  - Attractive metallophilic (aurophilic, argentophilic, cuprophilic, etc.)
      interactions play an important role in arrangement and stabilization of
      oligonuclear metal ion complexes. We report a combined experimental and
      theoretical assessment of aurophilic interactions in closed-shell gold(I) dimers.
      The experimental binding energies were obtained for charged
      [(LH)AuCl]+...[(L')AuCl] dimers (L is either a phosphine or an N-heterocyclic
      carbene ligand) in the gas phase. These energies served for benchmarking of
      correlated quantum chemical calculations (CCSD(T)-calibrated SCS-MP2/CBS method)
      that were then applied to neutral [(L)AuCl]...[(L')AuCl] dimers. The overall
      attractive interactions between monomeric units are in the order of 100-165 kJ
      mol-1 in the charged dimers and of 70-105 kJ mol-1 in the corresponding neutral
      dimers. In the neutral dimers, pure aurophilic interactions account for 25-30 kJ
      mol-1, the dipole-dipole interactions for 30-45 kJ mol-1, and the L...L' "inter
      ligand" dispersion interactions for 5-25 kJ mol-1. Energy of the aurophilic
      interactions is thus comparable or even larger than that of strong hydrogen
      bonds.

PMID- 29334455
TI  - Modulating the Molybdenum Coordination Sphere of Escherichia coli Trimethylamine
      N-Oxide Reductase.
AB  - The well-studied enterobacterium Escherichia coli present in the human gut can
      reduce trimethylamine N-oxide (TMAO) to trimethylamine during anaerobic
      respiration. The TMAO reductase TorA is a monomeric, bis-molybdopterin guanine
      dinucleotide (bis-MGD) cofactor-containing enzyme that belongs to the dimethyl
      sulfoxide reductase family of molybdoenzymes. We report on a system for the in
      vitro reconstitution of TorA with molybdenum cofactors (Moco) from different
      sources. Higher TMAO reductase activities for TorA were obtained when using Moco
      sources containing a sulfido ligand at the molybdenum atom. For the first time,
      we were able to isolate functional bis-MGD from Rhodobacter capsulatus formate
      dehydrogenase (FDH), which remained intact in its isolated state and after
      insertion into apo-TorA yielded a highly active enzyme. Combined
      characterizations of the reconstituted TorA enzymes by electron paramagnetic
      resonance spectroscopy and direct electrochemistry emphasize that TorA activity
      can be modified by changes in the Mo coordination sphere. The combination of
      these results together with studies of amino acid exchanges at the active site
      led us to propose a novel model for binding of the substrate to the molybdenum
      atom of TorA.

PMID- 29334456
TI  - Building Ion-Conduction Highways in Polymeric Electrolytes by Manipulating
      Protein Configuration.
AB  - Solid polymer electrolytes play a critical role in the development of safe,
      flexible, and all-solid-state energy storage devices. However, the low ion
      conductivity has been the primary challenge impeding them from practical
      applications. Here, we propose a new biotechnology to fabricate novel protein
      ceramic hybrid nanofillers for simultaneously boosting the ionic conductivity,
      mechanical properties, and even adhesion properties of solid polymer
      electrolytes. This hybrid nanofiller is fabricated by coating ion-conductive soy
      proteins onto TiO2 nanoparticles via a controlled denaturation process in
      appropriate solvents and conditions. It is found that the chain configuration and
      protein/TiO2 interactions in the hybrid nanofiller play critical roles in
      improving not only the mechanical properties but also the ion conductivity,
      electrochemical stability, and adhesion properties. Particularly, the ion
      conductivity is improved by one magnitude from 5 * 10-6 to 6 * 10-5 S/cm at room
      temperature. To understand the possible mechanisms, we perform molecular
      simulation to study the chain configuration and protein/TiO2 interactions.
      Simulation results indicate that the denaturation environment and procedures can
      significantly change the protein configuration and the protein/TiO2 interactions,
      both of which are found to be critical for the ion conductivity and mechanical
      properties of the resultant solid composite electrolytes. This study indicates
      that biotechnology of manipulating protein configuration can bring novel and
      promising strategies to build unique ion channels for fast ion conduction in
      solid polymer electrolytes.

PMID- 29334457
TI  - New Mechanism for Ferroelectricity in the Perovskite Ca2-xMnxTi2O6 Synthesized by
      Spark Plasma Sintering.
AB  - Perovskite oxides hosting ferroelectricity are particularly important materials
      for modern technologies. The ferroelectric transition in the well-known oxides
      BaTiO3 and PbTiO3 is realized by softening of a vibration mode in the cubic
      perovskite structure. For most perovskite oxides, octahedral-site tilting systems
      are developed to accommodate the bonding mismatch due to a geometric tolerance
      factor t = (A-O)/[?2(B-O)] < 1. In the absence of cations having lone-pair
      electrons, e.g., Bi3+ and Pb2+, all simple and complex A-site and B-site ordered
      perovskite oxides with a t < 1 show a variety of tilting systems, and none of
      them become ferroelectric. The ferroelectric CaMnTi2O6 oxide is, up to now, the
      only one that breaks this rule. It exhibits a columnar A-site ordering with a
      pronounced octahedral-site tilting and yet becomes ferroelectric at Tc ~ 650 K.
      Most importantly, the ferroelectricity at T < Tc is caused by an order-disorder
      transition instead of a displacive transition; this character may be useful to
      overcome the critical thickness problem experienced in all proper ferroelectrics.
      Application of this new ferroelectric material can greatly simplify the structure
      of microelectronic devices. However, CaMnTi2O6 is a high-pressure phase obtained
      at 7 GPa and 1200  degrees C, which limits its application. Here we report a new
      method to synthesize a gram-level sample of ferroelectric Ca2-xMnxTi2O6, having
      the same crystal structure as CaMnTi2O6 and a similarly high Curie temperature.
      The new finding paves the way for the mass production of this important
      ferroelectric oxide. We have used neutron powder diffraction to identify the
      origin of the peculiar ferroelectric transition in this double perovskite and to
      reveal the interplay between magnetic ordering and the ferroelectric displacement
      at low temperatures.

PMID- 29334458
TI  - Direct Electrochemical Vibrio DNA Sensing Adopting Highly Stable Graphene-Flavin
      Mononucleotide Aqueous Dispersion Modified Interface.
AB  - A biofunctionalized graphene nanohybrid was prepared by simultaneously sonicating
      graphene and riboflavin 5'-monophosphate sodium salt (FMNS). FMNS, as a
      biodispersant, showed an efficient stabilization for obtaining highly dispersed
      graphene nanosheets in an aqueous solution. Due to the superior dispersion of
      graphene and the excellent electrochemical redox activity of FMNS, a direct
      electrochemical DNA sensor was fabricated by adopting the inherent
      electrochemical redox activity of graphene-FMNS (Gr-FMNS). The comparison between
      using traditional electrochemical indicator ([Fe(CN)6]3-/4-) and using the self
      signal of Gr-FMNS was fully conducted to study the DNA-sensing performance. The
      results indicate that the proposed DNA-sensing platform displays fine
      selectivity, high sensitivity, good stability, and reproducibility using either
      [Fe(CN)6]3-/4- probe or the self-signal of Gr-FMNS. The two methods display the
      same level of detection limit: 7.4 * 10-17 M (using [Fe(CN)6]3-/4-) and 8.3 * 10
      17 M (using self-signal), respectively, and the latter exhibits higher
      sensitivity. Furthermore, the sensing platform also can be applied for the DNA
      determination in real samples.

PMID- 29334460
TI  - Multiple Stimuli Responses of Stereo-Isomers of AIE-Active Ethynylene-Bridged and
      Pyridyl-Modified Tetraphenylethene.
AB  - Luminescent molecules with aggregation-induced emission (AIE) property or AIE
      active luminogens (AIE-gens) are typical stimuli-responsive materials. Many AIE
      gens have shown luminescent responses to mechano-, thermo-, electro-, vapo-,
      and/or solvato-stimulus, but the detailed structure-property relationship has
      been addressed for only a few of them. Here, we report a tetraphenylethene (TPE)
      derivative with pyridyl modifiers and ethynylene bridges. The (Z)- and (E)
      isomers are clearly purified, and both of them are AIE-active and demonstrate
      multiple luminescent responses to external stimuli. Distinct from other reported
      TPE derivatives, the two isomers show negative solvatochromism due to the large
      dipole in the ground electronic state. By correlating with the single crystal
      structures, the subtle differences in quantum efficiency and emission peak
      wavelength of the solids of the (Z)- and (E)-isomers are rationally explained.
      Moreover, the ground powder of the (E)-isomer can recover its emission color from
      green to blue in the air at room temperature but the (Z)-isomer cannot. This
      difference is interpreted by a mechanism of water-triggered conformational
      variation, which depends on the hydrogen bond formation between pyridyl moieties
      and water molecules in the air. In addition to the reversible emission color
      changes by cyclic grinding-fuming treatments, both of the isomers exhibit a
      reversible luminescent response to acid-base treatments by switching the emission
      color between green (basic) and yellow (acid), owing to the incorporation of
      pyridyl units into the molecule. The unprecedented multiple stimuli-responsive
      behaviors and clear mechanism explanations allow this kind of AIE-gens to be
      promising smart materials.

PMID- 29334459
TI  - Development of CHARMM-Compatible Force-Field Parameters for Cobalamin and Related
      Cofactors from Quantum Mechanical Calculations.
AB  - Corrinoid cofactors such as cobalamin are used by many enzymes and are essential
      for most living organisms. Therefore, there is broad interest in investigating
      cobalamin-protein interactions with molecular dynamics simulations. Previously
      developed parameters for cobalamins are based mainly on crystal structure data.
      Here, we report CHARMM-compatible force field parameters for several corrinoids
      developed from quantum mechanical calculations. We provide parameters for
      corrinoids in three oxidation states, Co3+, Co2+, and Co1+, and with various
      axial ligands. Lennard-Jones parameters for the cobalt center in the Co(II) and
      Co(I) states were optimized using a helium atom probe, and partial atomic charges
      were obtained with a combination of natural population analysis (NPA) and
      restrained electrostatic potential (RESP) fitting approaches. The Force Field
      Toolkit was used to optimize all bonded terms. The resulting parameters,
      determined solely from calculations of cobalamin alone or in water, were then
      validated by assessing their agreement with density functional theory geometries
      and by analyzing molecular dynamics simulation trajectories of several corrinoid
      proteins for which X-ray crystal structures are available. In each case, we
      obtained excellent agreement with the reference data. In comparison to previous
      CHARMM-compatible parameters for cobalamin, we observe a better agreement for the
      fold angle and lower RMSD in the cobalamin binding site. The approach described
      here is readily adaptable for developing CHARMM-compatible force-field parameters
      for other corrinoids or large biomolecules.

PMID- 29334461
TI  - Enhanced Proton Loss from Neutral Free Radicals: Toward Carbon-Centered
      Superacids.
AB  - Radical centers close to protons are known to enhance their dissociation.
      Investigation of the generality of this radical enhanced deprotonation (RED
      shift) phenomenon, and the kinds of structures in which it operates, are
      reported. The pKas for sulfinic, sulfonic, pentan-2,4-dione, and Meldrum's acid
      species, with adjacent radicals centered on C-, N-, and O atoms, were computed by
      a DFT method from free energies of deprotonation. All series showed significant
      RED-shifts that increased with the electronegativity of the radical center. The
      hugely negative pKa obtained for a Meldrum's acid with an alkoxyl radical
      substituent showed it to belong to the superacid class. The ethyne unit was found
      to be uniquely effective at enhancing acidity and conducting RED-shifts through
      chains up to and beyond 20 atoms. These connector units enable a radical center
      to alter the pKa of a spatially remote acidic group. RED-shifted species were
      characterized by conjugate radical anions displaying site exchange of spin with
      electronic charge.

PMID- 29334463
TI  - Torquoselective Mechanochemical Activation of the Staudinger Reaction To Form
      beta-Lactams.
AB  - The Staudinger reaction yielding beta-lactam rings via [2 + 2] cycloaddition is a
      torquoselective reaction where the stereochemistry of the product can be steered
      by suitable substituents. Although the mechanochemical ring-opening of beta
      lactams has been investigated recently, the force-assisted synthesis of this
      important functional four-ring motif remains unexplored. As it will be
      computationally demonstrated, mechanochemical activation greatly reduces the
      barrier of the rate-limiting ring-closure step while, at the same time, preserves
      its torquoselectivity. This finding strongly suggests that strained four-membered
      rings can be readily incorporated in chain molecules using sonication techniques
      that greatly enhance reactivity while conserving selectivity.

PMID- 29334462
TI  - Pot-Economy Autooxidative Condensation of 2-Aryl-2-lithio-1,3-dithianes.
AB  - The autoxidative condensation of 2-aryl-2-lithio-1,3-dithianes is here reported.
      Treatment of 2-aryl-1,3-dithianes with n-BuLi in the absence of any electrophile
      leads to condensation of three molecules of 1,3-dithianes and formation of highly
      functionalized alpha-thioether ketones orthothioesters in 51-89% yields upon air
      exposure. The method was further expanded to benzaldehyde dithioacetals,
      affording corresponding orthothioesters and alpha-thioether ketones in 48-97%
      yields. The experimental results combined with density functional theory studies
      support a mechanism triggered by the autoxidation of 2-aryl-2-lithio-1,3
      dithianes to yield a highly reactive thioester that undergoes condensation with
      two other molecules of 2-aryl-2-lithio-1,3-dithiane.

PMID- 29334464
TI  - Asymmetric Synthesis of Secondary and Tertiary Propargylic Alcohols by Umpolung
      of Acetylenic Sulfones and ortho-Sulfinyl Carbanions.
AB  - The generation of diastereomerically enriched secondary benzyl propargyl alcohols
      by the asymmetric addition of ortho-sulfinylbenzyl carbanions to
      sulfonylacetylene derivatives via formation of a Csp-Csp3 bond is described. This
      reaction proceeds through an unusual alpha-attack (anti-Michael addition) of the
      ortho-sulfinylbenzyl carbanions, followed by elimination of the arylsulfonyl
      moiety. The scope of this alkynylation reaction is also discussed. Moreover, the
      development of a new approach for the synthesis of optically active tertiary
      benzylpropargyl alcohols is described, discussing the possible stereocourse of
      the reaction so as the influence of the ether 18-crown-6 and steric importance of
      acetylenic substituent.

PMID- 29334466
TI  - alpha-N-Heteroarylation and alpha-Azidation of Ketones via Enolonium Species.
AB  - Enolonium species, resulting from the umpolung of ketone enolates by Koser's
      hypervalent iodine reagents activated by boron trifluoride, react with a variety
      of nitrogen heterocycles to form alpha-aminated ketones. The reactions are mild
      and complete in 4-5 h. Additionally, alpha-azidation of the enolonium species
      takes place using trimethylsilyl azide as a convenient source of azide
      nucleophile.

PMID- 29334465
TI  - Design of a "Mini" Nucleic Acid Probe for Cooperative Binding of an RNA-Repeated
      Transcript Associated with Myotonic Dystrophy Type 1.
AB  - Toxic RNAs containing expanded trinucleotide repeats are the cause of many
      neuromuscular disorders, one being myotonic dystrophy type 1 (DM1). DM1 is
      triggered by CTG-repeat expansion in the 3'-untranslated region of the DMPK gene,
      resulting in a toxic gain of RNA function through sequestration of MBNL1 protein,
      among others. Herein, we report the development of a relatively short miniPEG
      gamma peptide nucleic acid probe, two triplet repeats in length, containing
      terminal pyrene moieties, that is capable of binding rCUG repeats in a sequence
      specific and selective manner. The newly designed probe can discriminate the
      pathogenic rCUGexp from the wild-type transcript and disrupt the rCUGexp-MBNL1
      complex. The work provides a proof of concept for the development of relatively
      short nucleic acid probes for targeting RNA-repeat expansions associated with DM1
      and other related neuromuscular disorders.

PMID- 29334469
TI  - Erratum.

PMID- 29334467
TI  - Robot-assisted upper extremity rehabilitation for cervical spinal cord injuries:
      a systematic scoping review.
AB  - : Abstact Purpose: To provide an overview of the feasibility and outcomes of
      robotic-assisted upper extremity training for individuals with cervical spinal
      cord injury (SCI), and to identify gaps in current research and articulate future
      research directions. MATERIALS AND METHODS: A systematic search was conducted
      using Medline, Embase, PsycINFO, CCTR, CDSR, CINAHL and PubMed on June 7, 2017.
      Search terms included 3 themes: (1) robotics; (2) SCI; (3) upper extremity.
      Studies using robots for upper extremity rehabilitation among individuals with
      cervical SCI were included. Identified articles were independently reviewed by
      two researchers and compared to pre-specified criteria. Disagreements regarding
      article inclusion were resolved through discussion. The modified Downs and Black
      checklist was used to assess article quality. Participant characteristics, study
      and intervention details, training outcomes, robot features, study limitations
      and recommendations for future studies were abstracted from included articles.
      RESULTS: Twelve articles (one randomized clinical trial, six case series, five
      case studies) met the inclusion criteria. Five robots were exoskeletons and three
      were end-effectors. Sample sizes ranged from 1 to 17 subjects. Articles had
      variable quality, with quality scores ranging from 8 to 20. Studies had a low
      internal validity primarily from lack of blinding or a control group. Individuals
      with mild-moderate impairments showed the greatest improvements on body
      structure/function and performance-level measures. This review is limited by the
      small number of articles, low-sample sizes and the diversity of devices and their
      associated training protocols, and outcome measures. CONCLUSIONS: Preliminary
      evidence suggests robot-assisted interventions are safe, feasible and can reduce
      active assistance provided by therapists. Implications for rehabilitation Robot
      assisted upper extremity training for individuals with cervical spinal cord
      injury is safe, feasible and can reduce hands-on assistance provided by
      therapists. Future research in robotics rehabilitation with individuals with
      spinal cord injury is needed to determine the optimal device and training
      protocol as well as effectiveness.

PMID- 29334470
TI  - Heterologous Expression of Rhizobial CelC2 Cellulase Impairs Symbiotic Signaling
      and Nodulation in Medicago truncatula.
AB  - The infection of legume plants by rhizobia is tightly regulated to ensure
      accurate bacterial penetration, infection, and development of functionally
      efficient nitrogen-fixing root nodules. Rhizobial Nod factors (NF) have key roles
      in the elicitation of nodulation signaling. Infection of white clover roots also
      involves the tightly regulated specific breakdown of the noncrystalline apex of
      cell walls in growing root hairs, which is mediated by Rhizobium leguminosarum
      bv. trifolii cellulase CelC2. Here, we have analyzed the impact of this
      endoglucanase on symbiotic signaling in the model legume Medicago truncatula.
      Ensifer meliloti constitutively expressing celC gene exhibited delayed nodulation
      and elicited aberrant ineffective nodules, hampering plant growth in the absence
      of nitrogen. Cotreatment of roots with NF and CelC2 altered Ca2+ spiking in root
      hairs and induction of the early nodulin gene ENOD11. Our data suggest that CelC2
      alters early signaling between partners in the rhizobia-legume interaction.

PMID- 29334471
TI  - Special Issue on "Constructing the Self Online".

PMID- 29334472
TI  - When Second Life Becomes Real Life: The Evolution of Self-Presentation.

PMID- 29334475
TI  - Abandonment of assistive products: assessing abandonment levels and factors that
      impact on it.
AB  - PURPOSE: To investigate the levels and factors that influence the abandonment of
      assistive products by users of a local reference rehabilitation center. METHODS:
      This observational study involved users who received services and assistive
      products provided by our center of rehabilitation. Users were identified using
      the records of the center and their responses about the abandonment were
      collected through face-to-face interviews. RESULTS: The abandonment level of
      assistive products was 19.38%. 83.5% of the users use at least one of the
      assistive products they have received. Rigid and folding frame wheelchairs, with
      and without postural support devices, as well as shower wheelchairs, presented
      the lowest abandonment levels, followed by canes and lower limb orthoses. Upper
      limb orthoses, Knee Ankle Foot Orthosis(KAFO), walkers, crutches and lower and
      upper limb prostheses all presented higher abandonment levels. CONCLUSION: The
      simultaneous use of mutiple assistive products, users perception on the
      importance of using them, and completing the rehabilitation treatment were found
      to impact on the short and long-term use of products. The study offers inputs to
      decision making and planning for assistive technology provision in developing
      countries with regard to expected demand and service delivery. Implications for
      Rehabilitation Data about the abandonment of assistive products in Sao Paulo,
      Brazil, could assist informing decision making on provision and servicing of
      these products in similar settings. The strong correlation found between
      abandonment levels and the simultaneous use of multiple devices should be taken
      into account by health professionals when prescribing assistive products and
      providing guidance to users. The need for follow up on the use of assistive
      products after discharge from rehabilitation treatment becomes strikingly clear,
      as data show that completing treatment is significantly relevant when evaluating
      abandonment levels. As assistive products users' perception about the importance
      of using these devices is shown to be significant in explaining abandonment, it
      is mandatory that health and rehabilitation professionals take it into account
      when providing guidance and training users.

PMID- 29334476
TI  - Biological Control of Botrytis cinerea: Interactions with Native Vineyard Yeasts
      from Washington State.
AB  - Native yeasts are of increasing interest to researchers, grape growers, and
      vintners because of their potential for biocontrol activity and their
      contributions to the aroma, flavor, and mouthfeel qualities of wines. To assess
      biocontrol activity, we tested 11 yeasts from Washington vineyards, representing
      isolates of Candida saitoana, Curvibasidium pallidicorallinum, Metschnikowia
      chrysoperlae, M. pulcherrima, Meyerozyma guilliermondii, Saccharomyces
      cerevisiae, and Wickerhamomyces anomalus, for ability to colonize Thompson
      Seedless grape berries, inhibit the growth of Botrytis cinerea in vitro, and
      suppress disease symptoms on isolated berries. The yeast-like fungus
      Aureobasidium pullulans was also included based on its known biocontrol activity
      against B. cinerea in studies on apple and grape. All yeast strains multiplied
      rapidly in grape berries and reached densities of over log 6 cells per wound as
      early as 2 days after inoculation with 200 cells. One of the Botrytis isolates
      used in this study was much less virulent than the others and was provisionally
      identified as B. prunorum based on multilocus sequence analysis. Suppression of
      the growth of B. cinerea isolates 111bb, 207a, 207cb, and 407cb occurred on
      berries treated with A. pullulans P01A006, Metschnikowia chrysoperlae P34A004 and
      P40A002, M. pulcherrima P01A016 and P01C004, Meyerozyma guilliermondii P34D003,
      and S. cerevisiae HNN11516. Inhibition of Botrytis isolates by the yeast strains
      was more common on berries than in vitro, suggesting the possibility that niche
      competition was a more likely biocontrol mechanism than antibiosis in planta.
      Metabolic profiling of yeast strains and B. cinerea isolates using Biolog YT
      plates revealed seven distinct metabolic groups. Furthermore, the yeast strains
      showed partial to complete tolerance to the commonly used fungicides fluopyram,
      triflumizole, metrafenone, pyraclostrobin, and boscalid. Implications of these
      findings for field deployment of native Washington yeasts as biocontrol agents
      against B. cinerea are discussed.

PMID- 29334477
TI  - Improvement of endothelial function by pitavastatin: a meta-analysis.
AB  - OBJECTIVE: Dyslipidemia is commonly associated with endothelial dysfunction and
      increased cardiovascular risk. Pitavastatin has been shown to reduce total and
      low-density lipoprotein cholesterol, to increase high-density lipoprotein (HDL)
      cholesterol and improve HDL function. Furthermore, several trials explored its
      effects on flow-mediated dilation (FMD), as an index of endothelial function. The
      authors evaluated the effect of pitavastatin therapy on FMD. METHODS: The authors
      performed a systematic review and meta-analysis of all clinical trials exploring
      the impact of pitavastatin on FMD. The search included PubMed-Medline, Scopus,
      ISI Web of Knowledge and Google Scholar databases. Quantitative data synthesis
      was performed using a random-effects model, with weighted mean difference (WMD)
      and 95% confidence interval (CI) as summary statistics. RESULTS: Six eligible
      studies comprising 7 treatment arms were selected for this meta-analysis.
      Overall, WMD was significant for the effect of pitavastatin on FMD (2.45%, 95%
      CI: 1.31, 3.60, p < 0.001) and the effect size was robust in the leave-one-out
      sensitivity analysis. CONCLUSION: This meta-analysis of all available clinical
      trials revealed a significant increase of FMD induced by pitavastatin.

PMID- 29334479
TI  - Correction: Mobile App-Based Interventions to Support Diabetes Self-Management: A
      Systematic Review of Randomized Controlled Trials to Identify Functions
      Associated with Glycemic Efficacy.

PMID- 29334478
TI  - Authorship Correction: Sampling Key Populations for HIV Surveillance: Results
      From Eight Cross-Sectional Studies Using Respondent-Driven Sampling and Venue
      Based Snowball Sampling.
AB  - [This corrects the article DOI: 10.2196/publichealth.8116.].

PMID- 29334481
TI  - Flexible and freestanding supercapacitor based on nanostructured poly(m
      aminophenol)/carbon nanofiber hybrid mats with high energy and power densities.
AB  - Nanostructured poly(m-aminophenol) (PmAP) coated freestanding carbon nanofiber
      (CNF) mats were fabricated through simple in situ rapid-mixing polymerization of
      m-aminophenol in the presence of a CNF mat for flexible solid-state
      supercapacitors. The surface compositions, morphology and pore structure of the
      hybrid mats were characterized by using various techniques, e.g., FTIR, Raman,
      XRD, FE-SEM, TEM, and N2 absorption. The results show that the PmAP nanoparticles
      were homogeneously deposited on CNF surfaces and formed a thin flexible hybrid
      mat, which were directly used to made electrodes for electrochemical analysis
      without using any binders or conductive additives. The electrochemical
      performances of the hybrid mats were easily tailored by varying the PmAP loading
      on a hybrid electrode. The PmAP/CNF-10 hybrid electrode with a relatively low
      PmAP loading (> 42 wt%) showed a high specific capacitance of 325.8 F g-1 and a
      volumetric capacitance of 273.6 F cm-3 at a current density of 0.5 A g-1,
      together with a specific capacitance retention of 196.2 F g-1 at 20 A g-1. The
      PmAP/CNF-10 hybrid electrode showed good cycling stability with 88.2% capacitance
      retention after 5000 cycles. A maximum energy density of 45.2 Wh kg-1 and power
      density of 20.4 kW kg-1 were achieved for the PmAP/CNF-10 hybrid electrode. This
      facile and cost-effective synthesis of a flexible binder-free PmAP/CNF hybrid mat
      with excellent capacitive performances encourages its possible commercial
      exploitation.

PMID- 29334480
TI  - Strategies for enhancing medical student resilience: student and faculty member
      perspectives.
AB  - Objectives: To improve programs aimed to enhance medical student resiliency, we
      examined both medical student and faculty advisor perspectives on resiliency
      building in an Asian medical school. Methods: In two separate focus groups, a
      convenience sample of 8 MD-PhD students and 8 faculty advisors were asked to
      identify strategies for enhancing resilience. Using thematic analysis, two
      researchers independently examined discussion transcripts and field notes and
      determined themes through a consensus process. They then compared the themes to
      discern similarities and differences between these groups. Results: Themes from
      the student suggestions for increasing resilience included "Perspective changes
      with time and experience", "Defining effective advisors," and "Individual paths
      to resiliency". Faculty-identified themes were "Structured activities to change
      student perspectives," "Structured teaching of coping strategies", and
      "Institution-wide social support". Students described themselves as individuals
      building their own resilience path and preferred advisors who were not also
      evaluators. Faculty, however, suggested systematic, structural ways to increase
      resilience. Conclusions: Students and advisors identified some common, and many
      distinct strategies for enhancing medical student resilience. Student/advisor
      discrepancies may exemplify a cultural shift in Singapore's medical education
      climate, where students value increased individualism and autonomy in their
      education. As medical schools create interventions to enhance resilience and
      combat potential student burnout, they should consider individually-tailored as
      well as system-wide programs to best meet the needs of their students and
      faculty.

PMID- 29334482
TI  - Carbon nanotubes within polymer matrix can synergistically enhance mechanical
      energy dissipation.
AB  - Safe operation and health of structures relies on their ability to effectively
      dissipate undesired vibrations, which could otherwise significantly reduce the
      life-time of a structure due to fatigue loads or large deformations. To address
      this issue, nanoscale fillers, such as carbon nanotubes (CNTs), have been
      utilized to dissipate mechanical energy in polymer-based nanocomposites through
      filler-matrix interfacial friction by benefitting from their large interface area
      with the matrix. In this manuscript, for the first time, we experimentally
      investigate the effect of CNT alignment with respect to reach other and their
      orientation with respect to the loading direction on vibrational damping in
      nanocomposites. The matrix was polystyrene (PS). A new technique was developed to
      fabricate PS-CNT nanocomposites which allows for controlling the angle of CNTs
      with respect to the far-field loading direction (misalignment angle). Samples
      were subjected to dynamic mechanical analysis, and the damping of the samples
      were measured as the ratio of the loss to storage moduli versus CNT misalignment
      angle. Our results defied a notion that randomly oriented CNT nanocomposites can
      be approximated as a combination of matrix-CNT representative volume elements
      with randomly aligned CNTs. Instead, our results points to major contributions of
      stress concentration induced by each CNT in the matrix in proximity of other CNTs
      on vibrational damping. The stress fields around CNTs in PS-CNT nanocomposites
      were studied via finite element analysis. Our findings provide significant new
      insights not only on vibrational damping nanocomposites, but also on their
      failure modes and toughness, in relation to interface phenomena.

PMID- 29334483
TI  - Latanoprost-induced Skin Hypopigmentation.

PMID- 29334484
TI  - In Reply: Is the Optic Nerve Head Structure Impacted by a Diagnostic Lumbar
      Puncture in Humans?

PMID- 29334485
TI  - In Reply: Latanoprost-induced Skin Hypopigmentation.

PMID- 29334486
TI  - Is the Optic Nerve Head Structure Impacted by a Diagnostic Lumbar Puncture in
      Humans?

PMID- 29334487
TI  - A Novel Hinged Scleral Patch Graft for the Repair of Overfiltration and Bleb
      Leaks.
AB  - INTRODUCTION: The repair of the scleral flap is often needed in cases of severe
      hypotony or bleb leaks with overfiltration. We present a simple novel technique
      to restore the hinged flap using a scleral patch graft. MATERIALS AND METHODS: We
      present 4 eyes of 4 patients who presented with hypotony [intraocular
      pressure(IOP) <6 mm Hg] from overfiltration secondary to loose scleral flap (2
      eyes) and bleb leak (2 eyes). A scleral patch from a human donor, preserved in
      95% ethanol, was cut in a trapezoidal shape and placed over the area of
      filtration after a conjunctival peritomy. The scleral graft was secured
      anteriorly with a single double-armed 9-0 nylon suture in a double-mattress
      manner so as to create a hinged flap. Permanent or releasable sutures were placed
      posteriorly to control aqueous outflow. RESULTS: All 4 patients had complete
      resolution of hypotony and bleb leaks with increase in their IOP to early teens.
      All maintained aqueous flow posteriorly with preservation of bleb function.
      CONCLUSION: Reestablishing the original anatomy of the hinged scleral flap can
      maintain bleb function without risk of overfiltration or loss of IOP control.
      This can be achieved through a simple repair using a scleral patch graft.

PMID- 29334488
TI  - Severe Intraocular Pressure Elevation After Intracameral Healon 5 Viscoelastic
      Support for Postoperative Hypotony After XEN Gel Stent Insertion.
AB  - PURPOSE: The purpose of this article was to describe (i) a novel case of severe
      intraocular pressure (IOP) elevation due to intracameral Healon 5 for management
      of early postoperative (post-op) hypotony following XEN Gel Stent insertion and
      (ii) the management of this complication. MATERIALS AND METHODS: A case report.
      RESULTS: A 52-year-old man, with primary open-angle glaucoma and suboptimal left
      IOP control on maximally tolerated medical therapy, was managed with XEN Gel
      Stent insertion at another tertiary eye unit. Post-op, the IOP was 2 mm Hg with a
      shallow anterior chamber (AC) and choroidal effusions. Intracameral injections of
      Provisc on post-op days 1 and 3 failed to reverse hypotony. At 1 week post-op,
      persistent clinically significant hypotony was managed with Healon 5 injection
      into the AC. Twelve hours later, the patient experienced significant pain and
      reduced vision and presented to a different tertiary eye unit, where left visual
      acuity was hand movements, IOP was 70 mm Hg with a deep AC (complete ophthalmic
      viscosurgical device fill with Healon 5) and a flat drainage bleb with no
      external drainage. Emergency AC washout of the Healon 5 was performed with
      resolution of symptoms, visual acuity, and IOP control. CONCLUSIONS: We caution
      against the use of intracameral Healon 5 in the management of post-op hypotony
      following XEN Gel Stent insertion, given the potential risk for extreme IOP
      elevation and sight loss.

PMID- 29334489
TI  - Association between arterial stiffness and wave reflection with subsequent
      development of placental-mediated diseases during pregnancy: findings of a
      systematic review and meta-analysis.
AB  - OBJECTIVE: We present a comprehensive systematic review of published literature
      to examine, whether arterial stiffness and wave reflection measurements during
      pregnancy differed between healthy patients and patients with placental-mediated
      diseases including preeclampsia (PET), small for gestational age (SGA), fetal
      death, and placental abruption, and a quantitative assessment of the findings
      using the meta-analysis approach. METHODS: We searched Medline, Embase, and The
      Cochrane Library for studies of arterial stiffness in pregnancy, analyzed
      pregnancy outcomes and conducted the meta-analysis of data evaluated by
      trimesters of pregnancy. Hemodynamic parameters evaluated included: pulse wave
      velocity (PWV), augmentation index (AIx), and augmentation index-75 (AIx-75).
      RESULTS: We screened 2806 citations, reviewed 36 studies and included nine (n =
      15 923) studies for further quantitative assessment. Compared with healthy
      pregnancy, measures of arterial stiffness and wave reflection were consistently
      increased among pregnant women who subsequently developed PET during all
      trimesters. In the first trimester, mean AIx-75 (%) in the PET group was
      significantly higher with estimated standardized mean difference (SMD) of 0.90
      [95% confidence intervals (95% CI) 0.07-1.73; P = 0.034]. In the second
      trimester, the PET group had significantly higher PWV (m/s) with estimated SMD of
      1.26 (95% CI 0.22-2.30; P = 0.018). Concerning the SGA group, mean AIx (%) was
      greater during the second trimester only: 65.5 (SD 15.6) vs. 57.0 (11.2), P <
      0.01. CONCLUSION: There is significant increase in arterial stiffness and wave
      reflection parameters among pregnant women who subsequently developed PET and SGA
      fetuses. Larger studies with consistent methodological designs are required to
      evaluate the role and usefulness of arterial stiffness and wave reflection
      measurements as a screening tool for placental-mediated diseases during
      pregnancy.

PMID- 29334490
TI  - Differential impact of local and regional aortic stiffness on left ventricular
      remodeling: a cardiovascular magnetic resonance study.
AB  - BACKGROUND: Left ventricular (LV) remodeling and aortic stiffness have
      independent predictive value for all causes and cardiovascular mortality. Because
      elastic properties of the arterial wall vary along the aortic pathway, we
      hypothesized that local and regional aortic stiffness could differently impact on
      LV remodeling. METHODS AND RESULTS: Regional aortic stiffness was determined from
      carotid-femoral pulse wave velocity (cfPWV) measured by aplanation tonometry.
      Aortic arch pulse wave velocity was measured by phase contrast cardiovascular
      magnetic resonance (CMR). Local stiffness was calculated in the ascending aorta
      pulse wave velocity (aaPWV) and descending aorta pulse wave velocity using
      central pulse pressure measurement, cine CMR acquisition, and surface change
      estimation. CMR LV remodeling was expressed as LV mass to end-diastolic volume
      ratio.We evaluated 146 study participants (41 +/- 15 years) free of overt
      cardiovascular disease. In stepwise multivariate regression analysis, cfPWV and
      aaPWV were significantly and independently correlated to mass to end-diastolic
      volume ratio (partial R = 0.07 and R = 0.10, respectively, all P < 0.005) after
      adjustment for age, sex, BMI, brachial mean blood pressure, and central pulse
      pressure. Descending aorta pulse wave velocity was correlated with mass to end
      diastolic volume ratio to a lower extent (R = 0.04, P = 0.0115) and aortic arch
      pulse wave velocity was not independently associated with mass to end-diastolic
      volume ratio. CfPWV and aaPWV were both independently associated with mass to end
      diastolic volume ratio, explaining 5 and 8% of mass to end-diastolic volume ratio
      variance, respectively. CONCLUSION: In study participants free of overt
      cardiovascular disease, stiffness of the ascending aorta representing the local
      proximal aortic function face to the LV and of the downstream aortic pathway
      assessed by cfPWV reflecting more advanced alterations of material properties
      involving the entire aorta, are independent determinants of LV remodeling after
      adjustment to age, BMI, mean blood pressure, and sex.

PMID- 29334491
TI  - A randomized titrate-to-target study comparing fixed-dose combinations of
      azilsartan medoxomil and chlorthalidone with olmesartan and hydrochlorothiazide
      in stage-2 systolic hypertension.
AB  - BACKGROUND: Azilsartan medoxomil (AZL-M), an angiotensin II receptor blocker, has
      been developed in fixed-dose combinations (FDCs) with chlorthalidone (CTD).
      OBJECTIVE/METHODS: We compared FDCs of AZL-M/CTD 20/12.5 mg once daily titrated
      to 40/25 mg if needed or AZL-M/CTD 40/12.5 mg once daily titrated to 80/25 mg if
      needed with an olmesartan medoxomil (OLM)-hydrochlorothiazide (HCTZ) 20/12.5 mg
      FDC once daily titrated to 40/25 mg if needed in a randomized, double-blind, 8
      week study of 1085 participants with clinic SBP 160-190 mmHg and DBP 119 mmHg or
      less. Titration to higher doses occurred at week 4 if BP was at least 140/90 mmHg
      (>=130/80 mmHg if diabetes or chronic kidney disease). The primary endpoint was
      change from baseline in clinic SBP; 24-h ambulatory BP monitoring was also
      measured. RESULTS: Greater reductions in clinic SBP from a baseline of 165 mmHg
      were observed (P < 0.001) in both AZL-M/CTD arms (-37.6 and -38.2 mmHg) versus
      OLM/HCTZ (-31.5 mmHg), despite greater dose titration in the OLM/HCTZ group. At 8
      weeks, both AZL-M/CTD FDCs reduced 24-h SBP more than OLM/HCTZ (-26.4 and -27.9
      versus -20.7 mmHg; both P < 0.001), and higher proportions in both AZL-M/CTD
      groups achieved target BP compared with the OLM/HCTZ group (69.4 and 68.9 versus
      54.7%, both P < 0.001). Adverse events leading to drug discontinuation occurred
      in 6.2, 9.5, and 3.1% with the AZL-M/CTD lower and higher doses, and OLM/HCTZ,
      respectively. CONCLUSION: This large, titration-to-target BP study demonstrated
      AZL-M/CTD FDCs to have superior antihypertensive efficacy compared with the
      maximum approved dose of OLM/HCTZ.

PMID- 29334493
TI  - Understanding Severe Maternal Morbidity: Hospital-based Review.
AB  - Cases of severe maternal morbidity (SMM) share similarities to maternal deaths,
      including increasing in frequency and having similar rates of preventability.
      This article will review steps to organizing and implementing standard reviews of
      all cases of SMM. These steps include create multidisciplinary SMM review
      committee; identify potential SMM cases and confirm true SMM; identify the
      morbidity; abstract and summarize data; present case to review committee for
      discussion; determine events leading to morbidity; determine opportunities to
      improve outcome; assess provider, system and patient factors in cases with
      opportunities to improve outcome; make recommendations; and effect change and
      evaluate improvement.

PMID- 29334492
TI  - Anti-IL-10-mediated Enhancement of Antitumor Efficacy of a Dendritic Cell
      targeting MIP3alpha-gp100 Vaccine in the B16F10 Mouse Melanoma Model Is Dependent
      on Type I Interferons.
AB  - The chemokine MIP3alpha (CCL20) binds to CCR6 on immature dendritic cells.
      Vaccines fusing MIP3alpha to gp100 have been shown to be effective in
      therapeutically reducing melanoma tumor burden and prolonging survival in a mouse
      model. Other studies have provided evidence that interleukin-10 (IL-10)
      neutralizing antibodies (alphaIL-10) enhance immunologic melanoma therapies by
      modulating the tolerogenic tumor microenvironment. In the current study, we have
      utilized the B16F10 syngeneic mouse melanoma model to demonstrate for the first
      time that a therapy neutralizing IL-10 enhances the antitumor efficacy of a
      MIP3alpha-gp100 DNA vaccine, leading to significantly smaller tumors, slower
      growing tumors, and overall increases in mouse survival. The additive effects of
      alphaIL-10 were not shown to be correlated to vaccine-specific tumor-infiltrating
      lymphocytes (TILs), total TILs, or regulatory T cells. However, we discovered an
      upregulation of IFNalpha-4 transcripts in tumors and a correlation of increased
      plasmacytoid dendritic cell numbers with reduced tumor burden in alphaIL-10
      treated mice. Interferon alpha receptor knockout (IFNalphaR1) mice received no
      benefit from alphaIL-10 treatment, demonstrating that the additional therapeutic
      value of alphaIL-10 is primarily mediated by type I IFNs. Efficient targeting of
      antigen to immature dendritic cells with a chemokine-fusion vaccine provides an
      effective anticancer therapeutic. Combining this approach with an IL-10
      neutralizing antibody therapy enhances the antitumor efficacy of the therapy in a
      manner dependent upon the activity of type I IFNs. This combination of a vaccine
      and immunomodulatory agent provides direction for future optimization of a novel
      cancer vaccine therapy.

PMID- 29334494
TI  - State-based Review of Maternal Deaths: The Ohio Experience.
AB  - Ohio established a Pregnancy-Associated Mortality Review system in 2010 to ensure
      that all maternal deaths are identified and preventive actions developed. The
      need for detailed and reliable information to supplement vital statistics data
      has led to the development of state-based and urban-based maternal death reviews.
      Although processes vary from state to state, in general, an expert panel is
      convened to review individual cases and make recommendations for systems change.
      This article describes the development and operation of Ohio's state-based
      maternal death review including interventions developed and actions taken based
      on review data.

PMID- 29334495
TI  - The ethics of interventional procedures for patients too ill for surgery.
AB  - PURPOSE OF REVIEW: Minimally invasive interventional procedures are increasingly
      popular options for patients who are high-risk candidates for open surgical
      procedures. It is unclear how to proceed in the rare circumstance of a
      complication during an interventional procedure, where addressing the
      complication would require exposing the patient to the full risk that was being
      avoided with the minimally invasive technique. This review provides
      recommendations on how to approach this paradoxical scenario. RECENT FINDINGS:
      Risk stratification, communication frameworks, and advanced care planning can
      facilitate shared decision-making between physicians and patients. Risk
      stratification may include mortality predictive models, disability and frailty
      scores, and patient-centered outcome studies. In the event of procedural
      complication or failure, aggressive surgical treatment or limited repair should
      be guided by patient preferences to best ensure value concordant care. SUMMARY:
      Interventional procedures, and emergent open surgery, should be offered as long
      as patients are fully informed about the benefits and risks, including the
      implications of potential life-sustaining treatments, and whether their
      respective goals of treatment are consistent with the intervention. Implementing
      this framework will require a cultural shift in physician attitudes to recognize
      that in some cases, nonintervention or less aggressive treatment may be a
      reasonable alternative to surgical intervention.

PMID- 29334496
TI  - Oxygen in the critically ill: friend or foe?
AB  - PURPOSE OF REVIEW: To examine the potential harmful effects of hyperoxia and
      summarize the results of most recent clinical studies evaluating oxygen therapy
      in critically ill patients. RECENT FINDINGS: Excessive oxygen supplementation may
      have detrimental pulmonary and systemic effects because of enhanced oxidative
      stress and inflammation. Hyperoxia-induced lung injury includes altered
      surfactant protein composition, reduced mucociliary clearance and histological
      damage, resulting in atelectasis, reduced lung compliance and increased risk of
      infections. Hyperoxemia causes vasoconstriction, reduction in coronary blood flow
      and cardiac output and may alter microvascular perfusion. Observational studies
      showed a close relationship between hyperoxemia and increased mortality in
      several subsets of critically ill patients. In absence of hypoxemia, the routine
      use of oxygen therapy in patients with myocardial infarction, stroke, traumatic
      brain injury, cardiac arrest and sepsis, showed no benefit but rather it seems to
      be harmful. In patients admitted to intensive care unit, a conservative oxygen
      therapy aimed to maintain arterial oxygenation within physiological range has
      been proved to be well tolerated and may improve outcome. SUMMARY: Liberal O2 use
      and unnecessary hyperoxia may be detrimental in critically ill patients. The
      current evidence supports the use of a conservative strategy in O2 therapy to
      avoid patient exposure to unnecessary hyperoxemia.

PMID- 29334497
TI  - Deep vein thrombosis and venous thromboembolism in trauma.
AB  - PURPOSE OF REVIEW: Deep vein thrombosis (DVT) and pulmonary embolus are major
      causes of hospital-related morbidity and mortality, and are recognized as
      complications in patients with traumatic injury. Despite the significant
      morbidity and mortality associated with DVTs, prophylaxis and treatment are still
      not well understood and remain the subject of research and debate. RECENT
      FINDINGS: Elements of the patient's history and physical examination, along with
      thromboelastography, can be used to predict patients who are at greatest risk of
      DVT and venous thromboembolism (VTE). Novel assays and biomarkers hold promise
      for more accurate evaluation of coagulation status. Patients with traumatic
      injury are routinely treated with either mechanical or pharmacological treatments
      to prevent DVT, and a growing body of evidence suggests that DVT prophylaxis
      should be initiated as early as possible in a patient's hospital course. SUMMARY:
      In trauma patients with traumatic injury, early identification and targeted VTE
      prophylaxis in trauma patients may prevent this life-threatening complication.

PMID- 29334498
TI  - Evidence-based Interpretation of Amyloid-beta PET Results: A Clinician's Tool.
AB  - BACKGROUND: Amyloid-beta positron emission tomography (PET) allows for in vivo
      detection of fibrillar amyloid plaques, a pathologic hallmark of Alzheimer's
      disease (AD). However, amyloid-beta PET interpretation is limited by the
      imperfect correlation between PET and autopsy, and the fact that it is positive
      in about 20% to 30% of cognitively normal individuals and non-AD dementias,
      especially when older or carrying the epsilon4 allele of apolipoprotein E
      (ApoE4). When facing a positive amyloid PET, clinicians have to evaluate the
      probability of a pathologic false positive as well as the probability of amyloid
      positivity being age-related, comorbid to a primary non-AD dementia
      (clinicopathologic false positive). These probabilities can be calculated to
      reach an evidence-based interpretation of amyloid-beta. As literature review and
      calculations cannot be easily performed in the day-to-day clinic, we propose a
      clinician friendly, evidence-based Bayesian approach to the interpretation of
      amyloid-beta PET results in the differential diagnosis of patients with cognitive
      impairment. METHODS: We defined AD as a clinicopathologic entity in which amyloid
      beta is the primary cause of cognitive impairment. We systematically reviewed the
      literature to estimate the sensitivity and specificity of amyloid-beta PET
      against neuropathologic examination. We inferred rates of clinicopathologic false
      positivity (non-AD dementia with comorbid amyloid) based on age-dependent and
      ApoE-dependent prevalence of amyloid positivity in normal individuals and AD
      patients provided in large meta-analyses published by the Amyloid Biomarker Study
      Group. We calculated positive predictive value (PPV) and negative predictive
      value (NPV) of amyloid-beta PET, which are presented in a clinician-friendly
      table. RESULTS: PPV of PET is highest in young ApoE4- patients with high pre-PET
      probability of AD. In older ApoE4+ patients with low pre-PET probability of AD,
      positive amyloid-beta PET scans must be interpreted with caution. A negative
      amyloid-beta PET makes a diagnosis of AD unlikely except in old patients with
      high pre-PET probability of AD. CONCLUSION: This evidence-based approach might
      provide guidance to clinicians and nuclear medicine physicians to interpret
      amyloid-beta PET results for early and differential diagnosis of patients with
      progressive cognitive impairment.

PMID- 29334499
TI  - Cognitive Function and its Risk Factors Among Older US Adults Living at Home.
AB  - BACKGROUND: The Montreal Cognitive Assessment (MoCA) has not been administered to
      a representative national sample, precluding comparison of patient scores to the
      general population and for risk factor identification. METHODS: A validated
      survey-based adaptation of the MoCA (MoCA-SA) was administered to a probability
      sample of home-dwelling US adults aged 62 to 90, using the National Social Life,
      Health, and Aging Project (n=3129), yielding estimates of prevalence in the
      United States. The association between MoCA-SA scores and sociodemographic and
      health-related risk factors were determined. RESULTS: MoCA-SA scores decreased
      with age, and there were substantial differences among sex, education, and
      race/ethnicity groups. Poor physical health, functional status, and depression
      were also associated with lower cognitive performance; current health behaviors
      were not. Using the recommended MoCA cut-point score for Mild Cognitive
      Impairment (MoCA score <26; MoCA-SA score <17), 72% (95% confidence interval, 69%
      to 74%) of older US adults would be classified as having some degree of cognitive
      impairment. CONCLUSIONS: Our results provide an important national estimate for
      interpreting MoCA scores from individual patients, and establish wide variability
      in cognition among older home-dwelling US adults. Care should be taken in
      applying previously-established MoCA cut-points to the general population,
      especially when evaluating individuals from educationally and ethnically diverse
      groups.

PMID- 29334500
TI  - Overexpression of u-Opioid Receptors in Peripheral Afferents, but Not in
      Combination with Enkephalin, Decreases Neuropathic Pain Behavior and Enhances
      Opioid Analgesia in Mouse.
AB  - BACKGROUND: The current study used recombinant herpes simplex virus type I to
      increase expression of u-opiate receptors and the opioid ligand preproenkephalin
      in peripheral nerve fibers in a mouse model of neuropathic pain. It was predicted
      that viral vector delivery of a combination of genes encoding the u-opioid
      receptor and preproenkephalin would attenuate neuropathic pain and enhance opioid
      analgesia. The behavioral effects would be paralleled by changes in response
      properties of primary afferent neurons. METHODS: Recombinant herpes simplex virus
      type 1 containing cDNA sequences of the u-opioid receptor, human
      preproenkephalin, a combination, or Escherichia coli lacZ gene marker (as a
      control) was used to investigate the role of peripheral opioids in neuropathic
      pain behaviors. RESULTS: Inoculation with the u-opioid receptor viral vector (n =
      13) reversed mechanical allodynia and thermal hyperalgesia and produced leftward
      shifts in loperamide (ED50 = 0.6 +/- 0.2 mg/kg vs. ED50 = 0.9 +/- 0.2 mg/kg for
      control group, n = 8, means +/- SD) and morphine dose-response curves (ED50 = 0.3
      +/- 0.5 mg/kg vs. ED50 = 1.1 +/- 0.1 mg/kg for control group). In u-opioid
      receptor viral vector inoculated C-fibers, heat-evoked responses (n = 12) and
      ongoing spontaneous activity (n = 18) were decreased after morphine application.
      Inoculation with both u-opioid receptor and preproenkephalin viral vectors did
      not alter mechanical and thermal responses. CONCLUSIONS: Increasing primary
      afferent expression of opioid receptors can decrease neuropathic pain-associated
      behaviors and increase systemic opioid analgesia through inhibition of peripheral
      afferent fiber activity.

PMID- 29334501
TI  - Practice Guidelines for Moderate Procedural Sedation and Analgesia 2018: A Report
      by the American Society of Anesthesiologists Task Force on Moderate Procedural
      Sedation and Analgesia, the American Association of Oral and Maxillofacial
      Surgeons, American College of Radiology, American Dental Association, American
      Society of Dentist Anesthesiologists, and Society of Interventional Radiology.

PMID- 29334502
TI  - Risk of Hepatitis B Virus Reactivation Among Patients Treated With Ledipasvir
      Sofosbuvir for Hepatitis C Virus Infection.
AB  - BACKGROUND: Direct acting antiviral (DAA) agents are the standard of care for
      treatment of hepatitis C virus (HCV)-infected individuals. Hepatitis B virus
      (HBV) reactivation during HCV treatment has been reported, the incidence and
      clinical outcome remains unclear. The aim of our study is to examine the risk of
      HBV reactivation in actively infected or previously exposed patients during or
      after HCV treatment with DAAs. METHODS: Adults with chronic HCV infection
      previously exposed or actively infected with HBV and treated with DAAs between
      December 2015 to 2016 were included. Electronic medical records were reviewed for
      HCV treatment dates, HCV treatment response, DAA used, HBV status, and concurrent
      HBV treatment. Primary end-point was to determine the risk of HBV reactivation
      during or up to 3 months after DAA treatment. RESULTS: We identified 283
      patients, and 100% of patients completed HCV treatment with ledipasvir
      sofosbuvir. 93% had HCV genotype-1 of whom 91% achieved sustained viral response
      at 12 weeks posttreatment (SVR-12). In total, 7% had HCV genotype-4 who achieved
      SVR-12 of 84%. Mean (+/-SD) age was 59.7 (+/-7) years, and 58% were male. A total
      of 45% of patients had hepatitis B core antibody (HBcAb) positive and hepatitis B
      surface antigen (HBsAg) negative. In total, 55% of patients had a positive HBsAg
      before HCV DAA treatment. No HBV reactivation was encountered in the (HBcAb)
      positive HBsAg-negative cohort nor in the (HBsAg) positive group with 95%
      confidence interval (0-0.023) and (0-0.019), respectively. CONCLUSION: In our
      study of patients with HCV and isolated hepatitis B core or HBsAg positivity, no
      HCV patients treated with DAA experienced HBV reactivation.

PMID- 29334503
TI  - Family history of autoimmune diseases and risk of gastric cancer: a national
      cohort study.
AB  - A personal history of autoimmune diseases is associated with an increased
      incidence of gastric cancer, but whether they share familial susceptibility is
      still unknown. The contribution of shared environmental or genetic factors toward
      the observed familial aggregation has not been determined. We used a few Swedish
      registers, including the Swedish Multigeneration Register and the Cancer
      Register, to examine the familial risk of gastric cancer among individuals with a
      family history of a set of autoimmune diseases. Standardized incidence ratios
      were used to calculate the relative risk. The overall risk of gastric cancer was
      1.22 (95% confidence interval: 1.14-1.30) among individuals with a sibling
      affected with any of the 33 autoimmune diseases. For specific disease, siblings
      of individuals with Crohn's diseases, diabetes type 1, Graves'/hyperthyroidism,
      myasthenia gravis, psoriasis, rheumatoid arthritis, sarcoidosis, and uncreative
      colitis showed an association with an increased incidence of gastric cancer, with
      a standardized incidence ratio ranging between 1.17 and 1.64. Familial
      aggregation was found only for corpus cancer. No association was observed between
      spouses. Gastric cancer, mainly corpus cancer, shares familial susceptibility
      with a few autoimmune diseases, suggesting that shared genetic polymorphisms may
      contribute toward both Helicobacter pylori infection and autoimmune diseases.

PMID- 29334504
TI  - Bradykinin receptors gene expression in white adipose tissue in nondiabetic
      patients with coronary artery disease.
AB  - OBJECTIVES: Adipose tissue plays a key role in cardiovascular physiology. Kinin
      receptors are important determinant of the effect of adiposity on endothelial
      function and cardiovascular function. We examined the gene expression levels of
      kinin receptors in the subcutaneous white adipose tissue (sWAT) of nondiabetic
      patients with and without coronary artery disease (CAD). PATIENTS AND METHODS: We
      evaluated 21 patients with CAD (13 men, age: 68+/-8 years) and 23 patients
      without CAD (15 men, age: 66+/-5 years) who underwent catheterization through the
      femoral route. sWAT biopsies were obtained from the site of vessel puncture
      before the procedure and analyzed for bradykinin receptor type 1 (BKR1) and 2
      (BKR2) gene expression by real-time quantitative PCR. RESULTS: Although BKR2
      expression levels did not differ significantly (413.12+/-532.41 in CAD patients
      vs. 378.33+/-534.45 in controls, P=NS), BKR1 expression in sWAT was significantly
      greater in patients with CAD (352.69+/-455.12 vs. 46.5+/-46.7, P<0.05). Notably,
      BKR1 gene expression levels showed a significant positive correlation with BMI
      (r=0.45, P<0.002) and total cholesterol levels (r=0.53, P<0.001), and a negative
      correlation with fasting blood glucose (r=-0.4, P=0.006). CONCLUSION: There is a
      divergence in BKR1 gene expression in sWAT between patients with and without CAD
      and is associated with metabolic parameters. More studies are needed to determine
      the pathophysiological role of BKRs in adipogenesis, fat expansion, and
      atheromatous disease.

PMID- 29334505
TI  - The association of chronic air pollutants with coronary artery spasm, vasospastic
      angina, and endothelial dysfunction.
AB  - BACKGROUND: We evaluated the effect of chronic exposure to air pollutants (APs)
      on coronary endothelial function and significant coronary artery spasm (CAS) as
      assessed by intracoronary acetylcholine (ACH) provocation test. PATIENTS AND
      METHODS: A total of 6430 patients with typical or atypical chest pain who
      underwent intracoronary ACH provocation test were enrolled. We obtained data on
      APs from the Korean National Institute of Environmental Research
      (http://www.nier.go.kr/). APs are largely divided into two types: particulate
      matter with aerodynamic diameter of less than or equal to 10 um in size (PM10)
      and gaseous pollutants such as nitrogen dioxide, sulfur dioxide, carbon monoxide,
      and ozone. The primary endpoint is the incidence of significant CAS and its
      associated parameters during ACH provocation test. RESULTS: The incidence of CAS
      was positively correlated with an exposure duration of PM10, whereas nitrogen
      dioxide, sulfur dioxide, carbon monoxide, and ozone were shown to be unrelated to
      CAS. During the ACH provocation test, as PM10 increased, the frequency of CAS was
      increased, and the incidence of transient ST-segment elevation was also
      increased. There was a trend toward higher incidence of spontaneous spasm as PM10
      increased. The mean exposure level of PM10 was 51.3+/-25.4 ug/m. The CAS risk
      increased by 4% when the level of PM10 increased by 20 ug/m by an adjusted Cox
      regression analysis. CONCLUSION: CAS incidence is closely related to exposure to
      PMs but not to gaseous pollutants. Particularly, higher exposure concentrations
      and longer exposure duration of PM10 increased the risk of CAS. These important
      findings provide a plausible mechanism that links air pollution to vasospastic
      angina and provide new insights into environmental factors.

PMID- 29334507
TI  - What's hot in heart valve disease 2018?

PMID- 29334506
TI  - Targeted biopsy: benefits and limitations.
AB  - PURPOSE OF REVIEW: To review the current literature regarding the role of
      multiparametric MRI and fusion-guided biopsies in urologic practice. RECENT
      FINDINGS: Fusion biopsies consistently show an increase in the detection of
      clinically significant cancers and decrease in low-risk disease that may be more
      suitable for active surveillance. Although, when to incorporate multiparametric
      MRI into workup is not clearly agreed upon, studies have shown a clear benefit in
      both biopsy naive and those with prior negative biopsies in determining the
      appropriate treatment strategy. More recently, cost-analysis models have been
      published that show that upfront MRIs are more cost-effective when considering
      missed cancers and treatment courses. SUMMARY: With improved accuracy over
      systematic biopsies, fusion biopsies are a superior method for detection of the
      true grade of cancer for both biopsy naive and patients with prior negative
      biopsies, choosing appropriate candidates for active surveillance, and monitoring
      progression on active surveillance.

PMID- 29334508
TI  - Practical valvular issues in patients requiring ventricular assist devices.
AB  - PURPOSE OF REVIEW: As ventricular assist device (VAD) therapy in patients with
      advanced heart failure continues to grow, experience with concomitant valvular
      diseases present either before or after VAD implantation continues to accrue. In
      this review, we discuss recent data and current practice as it pertains to the
      subject of concomitant valvular disease in patients requiring VADs. RECENT
      FINDINGS: Persistent aortic valve closure has been identified as a potential
      contributor to aortic valve 'disuse atrophy' resulting in valve degeneration.
      Dilation of the aortic root may be predictive of future development of aortic
      insufficiency. Novel echocardiographic parameters to identify the severity of
      aortic insufficiency following VAD implantation may be useful for risk
      stratification. Concomitant repair of significant mitral regurgitation may confer
      benefit to pulmonary vascular resistance and right ventricular function; however,
      this remains controversial. Concomitant repair of significant tricuspid
      regurgitation has not demonstrated early postoperative benefit nor survival
      benefit. Atrial fibrillation has emerged as a risk factor that may predict
      accelerated progression of postoperative tricuspid regurgitation. SUMMARY:
      Management of aortic insufficiency, mitral regurgitation or tricuspid
      regurgitation in patients requiring VADs continues to be the source of
      controversy. As experience accrues with varying strategies to prevent or manage
      these valvular lesions, our understanding of the impact of these strategies
      continues to evolve.

PMID- 29334509
TI  - Comparison of Stress and Strain Distribution Around Splinted and Nonsplinted 6-mm
      Short Implants in Posterior Mandible: A Finite Element Analysis Study.
AB  - PURPOSE: This study was designed to compare the biomechanical performance of
      splinted and nonsplinted short implants, in the posterior mandible, using finite
      element analysis. MATERIALS AND METHODS: Three-dimensional models of short
      implants with 2 different diameters (4 * 6 mm or 5 * 6 mm) were scanned, and
      CATIA (R21) was used to simulate the model of an edentulous lower jaw.
      Experimental groups were designed as follows: (1) D4L6-splinted (three 4 * 6-mm
      splinted implants), (2) D4L6-nonsplinted, (3) D5L6-splinted, and (4) D5L6
      nonsplinted. A 100 N load was applied, and stress and strain values in
      surrounding bone were analyzed in specific nodes using ANSYS software (16.1).
      RESULTS: The maximum stress values under axial load were found in D5L6-splinted
      model, and under oblique load, D5L6-nonsplinted model had the maximum stress
      values. Under axial load, D4L6-splinted model showed maximum strain values, but
      when oblique load was applied, D4L6-nonsplinted model had the maximum strain
      values. CONCLUSION: Splinting adjacent short implants may provide less bone
      strain and stress, especially at the presence of lateral forces. Increasing the
      implant diameter may be effective in strain reduction, but does not seem to
      reduce the bone stress, regardless of the direction of the load applied.

PMID- 29334510
TI  - Comparing peri-operative complications of paediatric and adult anaesthesia: A
      retrospective cohort study of 81 267 cases.
AB  - BACKGROUND: Comparisons of peri-operative complications associated with
      paediatric (<=16 years) and adult anaesthesia are poorly available, especially in
      which cardiac surgery, organ transplantation and neurosurgery are involved.
      OBJECTIVE: The aim of this study was to evaluate the nature and incidence of peri
      operative complications that might be due to anaesthesia and to identify
      independent risk factors for complications in children and adults, including
      those undergoing cardiac surgery, organ transplantation and neurosurgery. DESIGN:
      Retrospective cohort study. SETTING: The study was performed at the University
      Medical Centre Groningen in the 4 years between 1 January 2010 and the 31
      December 2013. MAIN OUTCOME MEASURES: Complications and their severity were
      graded according to the standard complication score (20 items) of the Dutch
      Society of Anaesthesia. Univariate and multivariate regression analysis was used
      to identify independent risk factors for the reported complications. RESULTS: A
      total of 81 267 anaesthetic cases were included. In the paediatric cohort, there
      were 410 (2.9%) complications and 1675 (2.5%) in the adults. In both cohorts age,
      American Society of Anaesthesiologists classification and emergency treatment
      were independent risk factors for complications. With respect to age, infants
      less than 1 year were at the highest risk, whereas in the adult cohort, increased
      age was related to a greater number of complications. The incidences of the
      specific complications were different between both cohorts. Upper airway
      obstruction was more frequently observed in paediatric patients (26%), whereas in
      the adults, complications with the highest incidence concerned conversion of
      regional-to-general anaesthesia (25%) and hypotension (17%). CONCLUSION: Risk
      factors for all peri-operative complications were similar for paediatric and
      adult anaesthesia. However, the incidence of specific complications differed
      between both age categories.

PMID- 29334511
TI  - Evaluation of recombinant factor VIIa, tranexamic acid and desmopressin to reduce
      prasugrel-related bleeding: A randomised, placebo-controlled study in a rabbit
      model.
AB  - BACKGROUND: Prasugrel is a thienopyridine that inhibits platelet aggregation more
      rapidly and effectively than clopidogrel, with an increased bleeding risk.
      OBJECTIVE: The current study aimed to evaluate the efficacy of three nonspecific
      haemostatic drugs - recombinant activated factor VII (rFVIIa), tranexamic acid
      and desmopressin (DDAVP) - to limit blood loss after administration of prasugrel
      in a rabbit model of bleeding while also evaluating any prothrombotic effects.
      DESIGN: Randomised, placebo-controlled study. SETTING: Faculty of Medicine,
      University of Geneva, Switzerland, in 2013. ANIMALS: Anaesthetised and
      artificially ventilated rabbits (n=56). INTERVENTIONS: Animals were randomly
      allocated to one of five groups: control (placebo-placebo), prasugrel-placebo,
      rFVIIa (prasugrel-rFVIIa 150 MUg kg), tranexamic acid (prasugrel-tranexamic acid
      20 mg kg) or DDAVP (prasugrel-DDAVP 1 MUg kg). Two hours after an oral prasugrel
      loading dose (4 mg kg), a stenosis and an injury were inflicted on the carotid
      artery to induce cyclic flow reductions (CFRs) due to thrombosis. Haemostatic
      drugs were administered during the ensuing observation period. MAIN OUTCOME
      MEASURES: Standardised hepatosplenic sections were performed to evaluate the
      primary endpoint of blood loss, monitored for 15 min. Ear-immersion bleeding time
      and incidence of CFRs were secondary endpoints. RESULTS: Prasugrel decreased ADP
      induced platelet aggregation (light transmission method) from 66 +/- 4% (mean +/-
      SD) to 41 +/- 7% (P < 0.001) and doubled blood loss: 10.7 g (10.1 to12.7) [median
      (interquartile range)] vs. 20.0 g (17.0 to 24.4), P = 0.003 in the control and
      prasugrel-placebo groups, respectively. rFVIIa, tranexamic acid and DDAVP reduced
      neither hepatosplenic blood loss [19.7 g (14.0 to 27.6), 25.2 g (22.6 to 28.7)
      and 22.9 g (16.8 to 28.8), respectively] nor bleeding time compared with placebo.
      Regarding safety, rVIIa induced three or more CFRs in 5/12 rabbits, vs. 0/12 in
      the prasugrel-placebo group (P = 0.037), whereas tranexamic acid and DDAVP did
      not increase them. CONCLUSION: The three studied haemostatic drugs rFVIIa,
      tranexamic acid and DDAVP failed to reduce prasugrel-related bleeding in this
      model. rFVIIa-treated rabbits were more prone to arterial thrombotic events.
      TRIAL REGISTRATION: NA.

PMID- 29334513
TI  - Opioid Use Disorders Attributed to Tramadol Among Egyptian University Students.
AB  - BACKGROUND: Tramadol use is an overwhelming problem in Egypt with tremendous
      medical and social consequences especially among youth. Use liability among
      Egyptian university students is underevaluated. This study aimed to estimate the
      prevalence and associated correlates of tramadol use among students from Zagazig
      University, Egypt. METHODS: A cross-sectional study included a total of 1135
      undergraduate students, from 10 colleges in Zagazig University. Participants were
      randomly selected and assessed for tramadol use using The Drug Use Disorders
      Identification Test (DUDIT) and The Drug Use Disorders Identification Test
      Extended (DUDIT-E). RESULTS: The prevalence of tramadol use was 12.3% among
      university students, with higher prevalence in male (20.2%) than female students
      (2.4%). The average age at onset of tramadol use was 17.6 +/- 2.1. Only 15% of
      the students with substance use were using tramadol alone whereas the rest (85%)
      were using at least 1 drug plus tramadol. One-fifth of these students started
      with tramadol as their first drug. Smoking, cannabis, and alcohol use predict
      tramadol use. About 60% of students who use tramadol had drug-related problems
      and 30% had dependence. Treatment readiness for tramadol use is negatively
      correlated with smoking and its duration. CONCLUSIONS: Tramadol use was common
      among university students, with higher prevalence among males. There is a
      considerable relationship between tramadol use, smoking, and use of other
      substances. Further population-based longitudinal studies need to investigate the
      causal relationship between tramadol use, smoking, and use of other substances.

PMID- 29334512
TI  - Association Between Alcohol Use and Angina Symptoms Among Outpatients From the
      Veterans Health Administration.
AB  - BACKGROUND: Alcohol use is associated with angina incidence, but associations
      between alcohol use and experience of angina among patients with coronary artery
      disease (CAD) have not been described. METHODS: Outpatients with CAD from 7
      clinics in the Veterans Health Administration were surveyed; alcohol use was
      measured using the validated Alcohol Use Disorders Identification Test
      Consumption scores categorized into 6 groups: nondrinking, low-risk drinking, and
      mild, moderate, severe, and very severe unhealthy alcohol use. Three domains of
      self-reported angina symptoms (frequency, stability, and physical function) were
      measured with the Seattle Angina Questionnaire. Linear regression models
      evaluated associations between alcohol use groups and angina symptoms. Models
      were adjusted first for age and then additionally for smoking, comorbidities, and
      depression. RESULTS: Patients (n = 8303) had a mean age of 66 years. In age
      adjusted analyses, a U-shaped association was observed between alcohol use groups
      and all angina outcomes, with patients in nondrinking and severe unhealthy
      alcohol groups reporting the greatest angina symptoms and lowest functioning.
      After full adjustment, no clinically important and few statistically important
      differences were observed across alcohol use in angina stability or frequency.
      Patients in the nondrinking group had statistically greater functional limitation
      from angina than those in all groups of unhealthy alcohol use, though differences
      were small. Patients in all groups of unhealthy alcohol use did not differ
      significantly from those with low-risk drinking. CONCLUSIONS: Alcohol use was
      associated with some small statistically but no clinically important differences
      in angina symptoms among patients with CAD. This cross-sectional study does not
      support a protective effect of low-level drinking on self-reported angina.

PMID- 29334514
TI  - Monitoring Depression Rates in an Urban Community: Use of Electronic Health
      Records.
AB  - OBJECTIVES: Depression is the most common mental health disorder and mediates
      outcomes for many chronic diseases. Ability to accurately identify and monitor
      this condition, at the local level, is often limited to estimates from national
      surveys. This study sought to compare and validate electronic health record (EHR)
      based depression surveillance with multiple data sources for more granular
      demographic subgroup and subcounty measurements. DESIGN/SETTING: A survey
      compared data sources for the ability to provide subcounty (eg, census tract
      [CT]) depression prevalence estimates. Using 2011-2012 EHR data from 2 large
      health care providers, and American Community Survey data, depression rates were
      estimated by CT for Denver County, Colorado. Sociodemographic and geographic
      (residence) attributes were analyzed and described. Spatial analysis assessed for
      clusters of higher or lower depression prevalence. MAIN OUTCOME MEASURE(S):
      Depression prevalence estimates by CT. RESULTS: National and local survey-based
      depression prevalence estimates ranged from 7% to 17% but were limited to county
      level. Electronic health record data provided subcounty depression prevalence
      estimates by sociodemographic and geographic groups (CT range: 5%-20%). Overall
      depression prevalence was 13%; rates were higher for women (16% vs men 9%),
      whites (16%), and increased with age and homeless patients (18%). Areas of higher
      and lower EHR-based, depression prevalence were identified. CONCLUSIONS:
      Electronic health record-based depression prevalence varied by CT, gender,
      race/ethnicity, age, and living status. Electronic health record-based
      surveillance complements traditional methods with greater timeliness and
      granularity. Validation through subcounty-level qualitative or survey approaches
      should assess accuracy and address concerns about EHR selection bias. Public
      health agencies should consider the opportunity and evaluate EHR system data as a
      surveillance tool to estimate subcounty chronic disease prevalence.

PMID- 29334515
TI  - Facilitating Adoption of an Electronic Documentation System.
AB  - Best practice recommends the integration of clinical documentation into the
      hospital electronic health record to support safe, efficient, and timely patient
      care. A major barrier to successful adoption and optimization of computerized
      documentation systems is user satisfaction. The purpose of this descriptive,
      performance improvement initiative was to implement and evaluate user
      satisfaction with an electronic documentation system to facilitate successful
      adoption. The Clinical Procedure Flowsheets application was implemented in a
      geriatric extended care unit of a large healthcare system. Rogers' Diffusion of
      Innovation and Davis' Technology Acceptance Model were used to guide system
      adoption and improve user experience of the innovation. The Perceived Usefulness
      and Perceived Ease of Use questionnaire was distributed to 24 nursing staff
      working in the unit 9 weeks after implementation. Results indicated that
      respondents perceived the Clinical Procedure Flowsheets as easy to use and useful
      in accomplishing their documentation tasks. The overall mean satisfaction score
      of 72.17 (SD, 12.13) implied a strong level of user acceptance. The positive
      perception of the nursing staff in the geriatric extended care unit suggests a
      high probability of system use that can enhance the documentation of patient
      care. Further research is recommended to evaluate factors related to system
      adoption and user satisfaction.

PMID- 29334516
TI  - Computer-Based Training in Eating and Nutrition Facilitates Person-Centered
      Hospital Care: A Group Concept Mapping Study.
AB  - Studies have shown that computer-based training in eating and nutrition for
      hospital nursing staff increased the likelihood that patients at risk of
      undernutrition would receive nutritional interventions. This article seeks to
      provide understanding from the perspective of nursing staff of conceptually
      important areas for computer-based nutritional training, and their relative
      importance to nutritional care, following completion of the training. Group
      concept mapping, an integrated qualitative and quantitative methodology, was used
      to conceptualize important factors relating to the training experiences through
      four focus groups (n = 43), statement sorting (n = 38), and importance rating (n
      = 32), followed by multidimensional scaling and cluster analysis. Sorting of 38
      statements yielded four clusters. These clusters (number of statements) were as
      follows: personal competence and development (10), practice close care
      development (10), patient safety (9), and awareness about the nutrition care
      process (9). First and second clusters represented "the learning organization,"
      and third and fourth represented "quality improvement." These findings provide a
      conceptual basis for understanding the importance of training in eating and
      nutrition, which contributes to a learning organization and quality improvement,
      and can be linked to and facilitates person-centered nutritional care and patient
      safety.

PMID- 29334517
TI  - The effect of arthropathies on illness perceptions, coping strategies, outcomes,
      and their changes over time in patients with inflammatory bowel disease: a 12
      month follow-up study.
AB  - OBJECTIVES: Arthropathies are a common extraintestinal manifestation (EIM) in
      inflammatory bowel disease (IBD). This study evaluated the differences in illness
      perceptions, coping strategies, and illness outcomes between patients with IBD
      with and without arthropathies at baseline and examined changes at 12 months in
      these variables in patients with arthropathies. METHODS: In total, 204 patients
      with (n=123) and without (n=81) arthropathies completed questionnaires at
      baseline and after 1 year, assessing illness perceptions, coping strategies,
      quality of life, and work and activity impairment. A linear regression analysis
      assessed the effect of arthropathies on these factors compared with patients
      without arthropathies. A mixed model analysis evaluated changes in illness
      perceptions, coping strategies, and outcomes in patients with arthropathies over
      time. RESULTS: Patients with arthropathies had more persistent thoughts on
      symptomatology and the variability of symptoms, held more negative views on the
      effects of illness, had heightened emotions that affected daily functioning, and
      had a poorer understanding of IBD than patients without arthropathies. Patients
      with arthropathies could more efficiently divert attention, felt more useful to
      others, and perceived a reduced physical and mental health and an increased
      activity impairment compared with patients without arthropathies. At follow-up,
      patients with arthropathies were more sceptical about the effectiveness of
      medical treatment but were better able to adapt their activities to their
      complaints compared with baseline. CONCLUSION: Patients with arthropathies in IBD
      adopt different illness perceptions and coping strategies and have different
      outcomes compared with patients without arthropathies, which is important to know
      when designing behavioral and physical interventions to improve functioning.

PMID- 29334518
TI  - Is ileocecal valve intubation essential for routine colonoscopic examination?
AB  - BACKGROUND: In this study, we aimed to assess the diagnostic yield of terminal
      ileum intubation during routine colonoscopy. MATERIALS AND METHODS: We routinely
      performed terminal ileum intubation in all patients who underwent colonoscopy at
      Dokuz Eylul University Hospital between February 2014 and June 2015. Two
      gastroenterology fellows performed colonoscopies in the Central Endoscopy Unit.
      Demographic data of patients, indications of colonoscopies, cecum and ileum
      intubation rate/time, and endoscopic and histopathologic findings of the terminal
      ileum were all assessed. RESULTS: A total of 1310 consecutive patients (726
      female and 584 male, median age: 55.79+/-14.29 years) underwent colonoscopy
      during this study period. The colonoscopy was successfully completed in 1144
      (87.3%) cases. The terminal ileum was successfully intubated in 1032 (90.2%)
      cases. The mean time taken to reach the ileum from the cecum was 63.08+/-64.16 s.
      Endoscopic abnormalities on the terminal ileum were present in 62 (6%) cases, and
      biopsies were taken from these patients. However, endoscopic abnormalities were
      found in 7 and 3.3% of patients who were symptomatic and asymptomatic,
      respectively. There were statistically significant differences between
      symptomatic and asymptomatic patients (P=0.02). Clinically significant
      histopathologic findings were observed in 22 cases, and 12 of the 22 cases were
      diagnosed as having Crohn's disease. CONCLUSION: Terminal ileum intubation is
      particularly indicated in symptomatic patients. In cases of chronic diarrhea,
      iron-deficiency anemia, abdominal pain, and suspected inflammatory bowel disease,
      terminal ileum intubation should be done.

PMID- 29334519
TI  - The Most Common Causes of Eye Pain at 2 Tertiary Ophthalmology and Neurology
      Clinics.
AB  - BACKGROUND: Eye pain is a common complaint, but no previous studies have
      determined the most common causes of this presenting symptom. Our objective was
      to determine the most common causes of eye pain in 2 ophthalmology and neurology
      departments at academic medical centers. METHODS: This was a retrospective cross
      sectional analysis and chart review at the departments of ophthalmology and
      neurology at the University Hospital Zurich (USZ), University of Zurich,
      Switzerland, and the University of Utah (UU), USA. Data were analyzed from
      January 2012 to December 2013. We included patients aged 18 years or older
      presenting with eye pain as a major complaint. RESULTS: Two thousand six hundred
      three patient charts met inclusion criteria; 742 were included from USZ and 1,861
      were included from UU. Of these, 2,407 had been seen in an ophthalmology clinic
      and 196 had been seen in a neurology clinic. Inflammatory eye disease
      (conjunctivitis, blepharitis, keratitis, uveitis, dry eye, chalazion, and
      scleritis) was the underlying cause of eye pain in 1,801 (69.1%) of all patients
      analyzed. Although only 71 (3%) of 2,407 patients had migraine diagnosed in an
      ophthalmology clinic as the cause of eye pain, migraine was the predominant cause
      of eye pain in the neurology clinics (100/196; 51%). Other causes of eye pain in
      the neurology clinics included optic neuritis (44 patients), trigeminal
      neuralgia, and other cranial nerve disorders (8 patients). CONCLUSIONS: Eye pain
      may be associated with a number of different causes, some benign and others sight
      or life-threatening. Because patients with eye pain may present to either a
      neurology or an ophthalmology clinic and because the causes of eye pain may be
      primarily ophthalmic or neurologic, the diagnosis and management of these
      patients often requires collaboration and consultation between the 2 specialties.

PMID- 29334520
TI  - Invited Commentary: Evaluation of Horner Syndrome in the MRI Era.
AB  - : This Invited Commentary discusses the following article: BACKGROUND:: To
      identify the etiologies of adult Horner syndrome (HS) in the MRI era using a
      targeted evaluation approach and to assess the value and yield of targeted
      imaging. METHODS: A retrospective chart review was performed of 200 adult
      outpatients with HS, confirmed with cocaine eyedrop testing. Patients were
      divided into subgroups based on the presence or absence of symptoms and those who
      did or did not receive additional testing with hydroxyamphetamine drops. Imaging
      was obtained based on pharmacologic localization and/or clinical evaluation. The
      etiology of HS and the yield of imaging were determined in all subgroups.
      RESULTS: Imaging showed causative lesions in 24 of 179 (12.84%) imaged patients
      with HS, and 13 (69.0%) were determined "idiopathic." Of the patients who
      underwent testing with hydroxyamphetamine drops (132 patients), 86 had a
      postganglionic localization with an imaging yield of 8.1%, and 46 had
      preganglionic cause with an imaging yield of 21.7%. Fifty-three patients (26.5%)
      never noticed ptosis/anisocoria before examination, and the imaging yield in this
      subgroup was 2.8%. Eighteen of the 200 patients (9.0%) had serious pathology,
      including carotid artery dissection, brain, or neck mass, and 6 of these (31.6%)
      had acute symptoms and/or pain. CONCLUSION: HS is most often idiopathic with
      serious pathology being relatively infrequent. When determining etiology, the
      absence of symptoms is not predictive of the pathology. However, acute onset of
      symptoms and/or pain are possible indicators for serious pathology. Localizing
      the lesion using hydroxyamphetamine drops whenever obtainable and available is
      still an efficient way to target imaging evaluation.

PMID- 29334521
TI  - New Educational Model to Promote Breast Cancer-Preventive Behaviors (ASSISTS):
      Development and First Evaluation.
AB  - BACKGROUND: The prevalence of breast cancer in Iran has increased. An effective
      approach to decrease the burden of breast cancer is prevention. OBJECTIVE: The
      aim of this study was to develop and evaluate an educational model, called the
      ASSISTS, for promoting breast cancer-preventive behaviors in women. METHODS: A
      multiphase method was used to develop the model designed to promote breast cancer
      prevention behaviors. A conceptual model was generated based on a secondary
      analysis of qualitative data. Then, a structural equation model technique was
      used to test the relationships among the model constructs. RESULTS: The analysis
      revealed that 7 constructs could be extracted, namely, perceived social support,
      attitude, motivation, self-efficacy, information seeking, stress management, and
      self-care. Based on these constructs, a conceptual model was built and tested
      using structural equation modeling. The model fit was good, and the model
      confirmed significant relationships among the 7 constructs of breast cancer
      prevention. CONCLUSION: Findings revealed that self-care behavior and stress
      management are influenced directly by attitude, motivation, self-efficacy,
      information seeking, and social support. In addition, women seek more information
      when they are motivated, have more self-efficacy, have a more positive attitude
      toward breast cancer prevention, and experience more social support. IMPLICATION
      FOR PRACTICE: Cancer nurses can be at the forefront of breast cancer prevention.
      Because they can play a pivotal role in providing information, they can reduce
      women's stress and increase their self-care behavior. In addition, their social
      support can positively influence Iranian women's attitude, motivation, and self
      care behavior. Furthermore, implementing educational programs based on this model
      might encourage women to practice preventive behaviors.

PMID- 29334522
TI  - Themes in Literature Related to Incidence, Risk, and Prevention of Cancer in
      Solid-Organ Transplantation Recipients on Immunosuppressive Therapy.
AB  - BACKGROUND: Solid-organ transplants provide a second chance to thousands of
      critically ill patients with end-organ failure each year. Immunosuppressants are
      administered to patients to prevent graft rejection of a transplanted organ, such
      as a heart, kidney, or liver, while placing the recipient at greater risk for
      infection and cancer. OBJECTIVE: The literature provides evidence of various
      cancers that have been found to develop in patients' posttransplantation. The
      purpose of this comprehensive review is to investigate the incidence, risk, and
      prevention of cancer in solid-organ transplantation recipients on
      immunosuppressive therapy. METHODS: Google Scholar, Cumulative Index to Nursing
      and Allied Health Literature and Ovid databases were searched to identify
      research articles in peer-reviewed journals from 2011 to 2016. Variables under
      examination included cancer risk, cancer type, incidence, demographic
      characteristics, prevention, screening modalities, and education tools. RESULTS:
      Six articles met the inclusion criteria. Results indicate that malignancy is a
      prominent postoperative finding in at least 4% to 5% of solid-organ transplant
      recipients, with evidence of various cancer types. Risk factors include male sex,
      increased age, number of years posttransplant, fair skin, white race, and UV
      exposure. Screening intervals and educational tools have been found to increase
      awareness and target those at greater risk. CONCLUSION: Skin cancer and non
      Hodgkin lymphoma were the most commonly diagnosed cancers in transplant
      recipients. IMPLICATIONS FOR PRACTICE: Practitioners may find utility in
      screening tools, self-examination education for patients, and follow-up protocols
      to prevent further complications in this patient population. Early detection of
      cancer and those at risk may help decrease morbidity and mortality rates in organ
      recipients.

PMID- 29334523
TI  - Not a Straight Line-Patients' Experiences of Prostate Cancer and Their Journey
      Through the Healthcare System.
AB  - BACKGROUND: Cancer and its treatment can severely impact quality of life, giving
      rise to complex needs with respect to follow-up care. To support patient needs
      and increase efficiency of care with limited resources, the Swedish government
      has launched national reforms to redesign cancer care pathways. OBJECTIVE: The
      aim of this study was to explore how prostate cancer patients experience their
      journey through the healthcare system when their care is provided according to
      the standardized care pathway, as described in healthcare policy documents.
      METHODS: A qualitative, descriptive approach with individual interviews was used.
      A template of a standardized prostate cancer pathway, created together with
      healthcare professionals, was used during interviews. Fourteen interviews were
      conducted with prostate cancer patients all operated on at a midsized hospital in
      southeast Sweden between October 2015 and April 2016. The interviews were
      analyzed with qualitative content analysis and illustrated in a patient journey
      map. RESULTS: We identified an overall theme, "walking a tightrope," consisting
      of 4 categories: "waiting," "becoming familiar with a troublesome body,"
      "adjusting to a different life," and "information challenges." CONCLUSIONS: The
      clinical implementation of the standardized care pathway is described as a
      straight path through care, but patients described their experiences as walking a
      tightrope. Lack of information, especially about cancer treatment and its adverse
      effects, was the most common experience. IMPLICATIONS FOR PRACTICE: Our findings
      indicate areas where further healthcare tools could improve patient experiences
      of cancer treatment. This could include offering individualized information and
      tools to increase patient empowerment, as well as patient/caregiver collaboration
      (co-care).

PMID- 29334524
TI  - Leveraging Linkage of Cohort Studies With Administrative Claims Data to Identify
      Individuals With Cancer.
AB  - BACKGROUND: In an effort to overcome quality and cost constraints inherent in
      population-based research, diverse data sources are increasingly being combined.
      In this paper, we describe the performance of a Medicare claims-based incident
      cancer identification algorithm in comparison with observational cohort data from
      the Nurses' Health Study (NHS). METHODS: NHS-Medicare linked participants' claims
      data were analyzed using 4 versions of a cancer identification algorithm across 3
      cancer sites (breast, colorectal, and lung). The algorithms evaluated included an
      update of the original Setoguchi algorithm, and 3 other versions that differed in
      the data used for prevalent cancer exclusions. RESULTS: The algorithm that
      yielded the highest positive predictive value (PPV) (0.52-0.82) and kappa
      statistic (0.62-0.87) in identifying incident cancer cases utilized both Medicare
      claims and observational cohort data (NHS) to remove prevalent cases. The
      algorithm that only used NHS data to inform the removal of prevalent cancer cases
      performed nearly equivalently in statistical performance (PPV, 0.50-0.79; kappa,
      0.61-0.85), whereas the version that used only claims to inform the removal of
      prevalent cancer cases performed substantially worse (PPV, 0.42-0.60; kappa, 0.54
      0.70), in comparison with the dual data source-informed algorithm. CONCLUSIONS:
      Our findings suggest claims-based algorithms identify incident cancer with
      variable reliability when measured against an observational cohort study
      reference standard. Self-reported baseline information available in cohort
      studies is more effective in removing prevalent cancer cases than are claims data
      algorithms. Use of claims-based algorithms should be tailored to the research
      question at hand and the nature of available observational cohort data.

PMID- 29334525
TI  - Temporal Patterns of Exposure to Asbestos and Risk of Asbestosis: An Analysis of
      a Cohort of Asbestos Textile Workers.
AB  - OBJECTIVE: The aim of the study was to assess the risk of asbestosis death based
      on the temporal pattern of exposure to asbestos. METHODS: We followed up a cohort
      of asbestos textile workers, employed in 1946 to 1984, until November 2013. We
      measured the duration of the employment, the time since last employment (TSLE),
      the age, and the year of first employment. Hazard ratios (HR) were estimated
      through multivariable Cox regression models. RESULTS: We observed 51 asbestosis
      deaths among 1823 workers. The HR of asbestosis death increased with exposure
      duration (HR 2.4 for >=15 years compared with <5 years, P trend = 0.014) and
      declined with TSLE (HR 0.3 for >=25 compared with <5 years, P = 0.004). The risk
      of asbestosis mortality strongly declined for exposure starting after 1968.
      CONCLUSIONS: The risk of asbestosis death strongly declines in the decades after
      cessation of the exposure.

PMID- 29334526
TI  - Airborne Particulate Matter: Human Exposure and Health Effects.
AB  - OBJECTIVE: Exposure to airborne particulate matter (PM) is estimated to cause
      millions of premature deaths annually. This work conveys known routes of exposure
      to PM and resultant health effects. METHODS: A review of available literature.
      RESULTS: Estimates for daily PM exposure are provided. Known mechanisms by which
      insoluble particles are transported and removed from the body are discussed.
      Biological effects of PM, including immune response, cytotoxicity, and
      mutagenicity, are reported. Epidemiological studies that outline the systemic
      health effects of PM are presented. CONCLUSION: While the integrated, per capita,
      exposure of PM for a large fraction of the first-world may be less than 1 mg per
      day, links between several syndromes, including attention deficit hyperactivity
      disorder (ADHD), autism, loss of cognitive function, anxiety, asthma, chronic
      obstructive pulmonary disease (COPD), hypertension, stroke, and PM exposure have
      been suggested. This article reviews and summarizes such links reported in the
      literature.

PMID- 29334527
TI  - Transanal Minimally Invasive Anal Canal Polyp Resection.
AB  - Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are
      operative endoscopies that have been performed since a long time. Recently, an
      evolution of laparoscopy called transanal minimally invasive surgery began to be
      popularized, and it can be adopted in the face of difficult cases for EMR/ESD. In
      this video, a 36-year-old woman was submitted to transanal minimally invasive
      surgery resection, after unsuccessful ESD, for a 2-cm polyp located anteriorly in
      the anal canal, just beyond the pectineal line. Preoperative workup showed a uT1m
      versus T1sm N0 M0 lesion. The procedure was performed with a new reusable
      transanal platform and a monocurved coagulating hook and grasping forceps. The
      operative time was 90 minutes. No perioperative complications were registered,
      and the patient was discharged on postoperative day 1. The pathologic report
      showed a villotubular adenoma with high-grade dysplasia and distant-free margins.
      After 1 year, the patient was going well, without any recurrent disease.
      Transanal minimally invasive surgery resection is a good alternative to
      conventional endoscopic therapies, allowing a meticulous dissection under the
      magnified operative field's exposure, and a mucosal-submucosal flap closure under
      satisfactory surgeon's ergonomics.

PMID- 29334529
TI  - Midterm Outcome of Kidney Transplantation From Donors With Thin Basement Membrane
      Nephropathy.
AB  - BACKGROUND: Thin basement membrane nephropathy (TBMN) is the most common cause of
      persistent glomerular hematuria. Most individuals with TBMN show a benign course,
      although it can be difficult to distinguish it from early stages of progressive
      renal diseases. However, only limited studies address the prognosis of donors
      with TBMN and their recipients. METHODS: From 2007 to 2016, 11 recipients
      received kidney grafts from donors with TBMN, and their clinical data were
      analyzed retrospectively. Follow-up protocol kidney biopsies were given to the
      recipients at 10 days and 1 year after transplantation. The donors were also
      received a follow-up evaluation of their renal function and were interviewed via
      telephone survey. RESULTS: All donors were living, and their kidney grafts showed
      TBMN on pretransplantation biopsy. The recipients were followed for 57.4 +/- 28.6
      months posttransplantation. Seven recipients showed acute rejection by a median
      of 9.7 months, and all recipients recovered their renal function after treatment.
      Although 1 kidney failed due to graft arterial occlusion, the functions of the
      others were preserved during the follow-up period. The donors were followed for
      41.0 +/- 39.1 months and additionally contacted via telephone survey (in total,
      56.8 +/- 32.0 months). All the donors maintained their renal function upon
      clinical follow-up without significant complications and denied any discomfort at
      the time of the telephone interview. CONCLUSIONS: Kidney transplant donors with
      TBMN and their recipients maintained their renal function through midterm follow
      up without significant complications. Therefore, kidney transplantation from
      donors with TBMN could be a safe option.

PMID- 29334528
TI  - Comparison of Laparoscopic and Open Pancreaticoduodenectomy for the Treatment of
      Nonpancreatic Periampullary Adenocarcinomas.
AB  - BACKGROUND: Laparoscopic pancreaticoduodenectomy (LPD), a surgical option for
      nonpancreatic periampullary adenocarcinoma (NPPA), is a complex procedure that
      has become increasing popular. However, there is no consensus as to whether this
      technique should be performed routinely. Our aim was to evaluate the outcomes of
      LPD compared with open pancreaticoduodenectomy (OPD). MATERIALS AND METHODS: From
      October 2010 to September 2015, 58 LPDs were performed to treat NPPA and were
      compared with 58 OPDs, which can theoretically be carried out by laparoscopic
      approach. Patients were also matched based on their demographic data and
      pathologic diagnosis. Demographic information, intraoperative and postoperative
      data, pathologic data, and follow-up evaluation data were collected at our
      center. RESULTS: All patients had a median follow-up of 34 months (range, 8 to 60
      mo). Overall median survival during the study between the groups was not
      different (P=0.760). No significant differences between the 2 groups were found
      in terms of patient demographics, short-term complications, pathologic outcomes,
      or tumor-node-metastasis stage. With regard to operative time, the LPD group was
      slightly longer than the OPD group (P<0.001). There were significant differences
      between groups in the time to the first passage of flatus and the time to oral
      intake (P<0.001). However, no differences were seen in blood loss, length of
      intensive care unit stay, node positive, or R0 resection between the laparoscopic
      and open groups. CONCLUSIONS: This study found that LPD is a feasible, safe, and
      effective method for the treatment of NPPA compared with OPD and may be a
      preferred method for surgeons to choose.

PMID- 29334530
TI  - Antegrade Arterial and Portal Flushing Versus Portal Flushing Only for Right Lobe
      Live Donor Liver Transplantation-A Randomized Control Trial.
AB  - BACKGROUND: In live donor liver transplantation portal flush only of the graft is
      done on the bench. There are no data on antegrade arterial flush along with
      portal flush of the graft. METHODS: Consecutive patients undergoing elective
      right lobe live donor liver transplantation were block-randomized to receive
      either portal flush only or both portal and antegrade arterial flush. The primary
      objectives were safety, rate of early allograft dysfunction (EAD), and impact on
      vascular and biliary complications. RESULTS: After randomization, there were 40
      patients in each group. Both groups had comparable preoperative, intraoperative,
      and donor variables. There were no adverse events related to arterial flushing.
      The portal and antegrade arterial flush group had significantly lower
      postoperative bilirubin on days 7, 14, and 21 (all P < 0.05), EAD (P = 0.005),
      intensive care unit/high dependency unit (P = 0.01), and hospital stay (P =
      0.05). This group also had lower peak aspartate aminotransferase (P = 0.07),
      alanine aminotransferase (P = 0.06) and lower rates of sepsis (P = 0.08) trending
      toward statistical significance. Portal and antegrade arterial flush groups had
      lower ascitic fluid drainage and in-hospital mortality. Arterial and biliary
      complications were not statistically different in the 2 groups. Multivariate
      analysis of EAD showed portal with antegrade arterial flush was associated with
      lower rate (P = 0.007), whereas model for end-stage liver disease Na (P = 0.01)
      and donor age (P = 0.03) were associated with a higher rate of EAD. CONCLUSIONS:
      Portal with antegrade arterial flushing of right lobe live liver grafts is safe,
      significantly decreases postoperative cholestasis, EAD, intensive care unit/high
      dependency unit, and hospital stay and is associated with lower rates of sepsis,
      ascitic drainage and inhospital mortality in comparison to portal flush only.

PMID- 29334531
TI  - Dangerously numb: opioids, benzodiazepines, chronic pain, and posttraumatic
      stress disorder.

PMID- 29334532
TI  - Cost-effectiveness and Improved Parent and Provider Satisfaction With Outpatient
      Management of Pediatric Oncology Patients, With Low-risk Fever and Neutropenia.
AB  - On the basis of significant evidence for safety, the international pediatric
      fever and neutropenia committee recommends the identification and management of
      patients with "low-risk fever and neutropenia" (LRFN), outpatient with oral
      antibiotics, instead of traditional inpatient management. The aim of our study
      was to compare the cost-per-patient with these 2 strategies, and to evaluate
      parent and provider satisfaction with the outpatient management of LRFN. Between
      March 2016 and February 2017, 17 LRFN patients (median absolute neutrophil count,
      90/MUL) were managed at a single institution, per new guidelines. Fifteen
      patients were discharged on presentation or at 24 to 48 hours postadmission on
      oral levofloxacin, and 2 were inadvertently admitted off protocol. The mean cost
      of management for the postimplementation cohort was compared with a historic
      preimplementation control group. Satisfaction surveys were completed by parents
      and health care providers of LRFN patients. The mean total cost of an LRFN
      episode was $12,500 per patient preimplementation and $6168 postimplementation, a
      decrease of $6332 (51%) per patient. All parents surveyed found outpatient follow
      up easy; most (12/14) parents and all (16/16) providers preferred outpatient
      management. Outpatient management of LRFN patients was less costly, and was
      preferred by a majority of parents and all health care providers, compared with
      traditional inpatient management.

PMID- 29334533
TI  - The Moonshot Initiative: Randomized, Controlled Trials, and Its Impact in
      Pediatric Oncology.

PMID- 29334534
TI  - Symptomatic Hyperammonemia With Erwinia chrysanthemi-derived Asparaginase in
      Pediatric Leukemia Patients.
AB  - Erwinia chrysanthemi-derived asparaginase is increasingly integral to acute
      lymphoblastic leukemia therapy. In our series, 16% of patients developed
      symptomatic hyperammonemia following Erwinia administration with symptoms
      including refractory nausea, vomiting, profound fatigue, malaise, and coma. This
      series of patients receiving Erwinia indicates higher than expected incidence of
      hyperammonemia, correlation between ammonia and asparaginase levels and
      therapeutic asparaginase activity levels despite dose reduction. The series
      provides evidence for investigation into which patients require intervention to
      prevent toxicity, which patients may have ammonia levels used as an asparaginase
      activity surrogate and which patients may achieve equivalent efficacy with
      abridged dosing.

PMID- 29334535
TI  - Simultaneous Presentation of Wilms' Tumor and Contralateral Ganglioneuroma in a
      Child: Case Report and Literature Review.
AB  - We demonstrate a 4-year-old girl who presented with progressive, asymmetrical,
      firm abdominal distention and was diagnosed with synchronous Wilms' tumor and
      left para-aortic ganglioneuroma (GN). Although synchronous tumors in the
      pediatric population are commonly associated with malignancy-predisposing
      syndromes, the patient in question was found to be otherwise healthy and had no
      clinical evidence nor family history of a syndrome. This case is the second one
      in the literature diagnosed with synchronous presentation of Wilms' tumor and GN
      in a previously healthy child. In addition, a GN foci presumed to be a previous
      metastasis of a neurogenic tumor that subsequently matured to GN was depicted
      within a left para-aortic lymph node. We aimed to emphasize an extremely rare
      synchronous occurrence of these embryonal tumors, increase the awareness of
      physicians, and discuss the radiologic differential diagnosis and management.

PMID- 29334536
TI  - Nationwide Trend Analysis of Pediatric Inpatients With Immune Thrombocytopenia in
      the United States.
AB  - BACKGROUND: Several studies have reported the epidemiology of immune
      thrombocytopenia (ITP) among children in the United States and other countries.
      However, recent trends in ITP among hospitalized children and hospital course
      remain unknown at a national level in the United States. METHOD: Hospital
      discharge records of patients with ITP aged 19 years and younger were obtained
      for the years 2003, 2006, 2009, and 2012 using the Kids' Inpatient Database. Data
      were weighted to estimate the annual hospitalization rates in the United States
      with trend analyses. Multivariable regression models were used to ascertain
      trends of health care utilizations, hospitalization costs, and length of stay.
      RESULTS: Total annual hospitalization rates due to ITP ranged from 6.13 per
      100,000 children in 2003 to 6.22 per 100,000 children in 2012 (Ptrend=0.86). The
      lowest proportions of hospitalizations were observed in August. The proportions
      of inpatients treated with intravenous immunoglobulin increased from 18.5% in
      2003 to 39.9% (Ptrend< 0.001), while those examined with bone marrow aspiration
      decreased from 7.8% in 2003 to 6.5% in 2012 (Ptrend=0.01). Total hospitalization
      costs and length of stay changed from $6147 and 3.78 days in 2003 to $9328 and
      2.55 days in 2012. CONCLUSIONS: We provided insights of epidemiology of ITP and
      health care utilizations in the United States. Further studies, including cost
      effective analyses, will be required to justify the increasing trends in health
      care costs and intravenous immunoglobulin.

PMID- 29334537
TI  - Isolated Central Nervous System Chloroma as a Presenting Sign of Relapsed
      Pediatric Acute Lymphoblastic Leukemia.
AB  - Central nervous system (CNS) chloromas are an exceedingly rare presentation of
      CNS relapse in acute lymphoblastic leukemia (ALL). We report a relapsed ALL
      patient who presented with 2 separate chloromas and cerebrospinal fluid
      lymphoblastocytosis, and outline a treatment plan of systemic chemotherapy and
      CNS-directed radiation therapy. A review of the literature indicates that
      multiagent chemotherapy combined with CNS radiotherapy is effective, with
      hematopoietic stem cell transplantation used in half of reported cases. We
      conclude that intensive systemic multiagent chemotherapy with CNS-directed
      radiation therapy can be successfully used to treat relapsed pediatric ALL with
      CNS lymphoblastic chloroma.

PMID- 29334538
TI  - Sickle Cell Trait Testing Should Not Be a Player in NCAA Athletics: Examining the
      Media's Role in Disseminating Awareness and Information.

PMID- 29334539
TI  - Gelatin-Based Hemostatic Agents: Histopathologic Differences.
AB  - PURPOSE: To delineate the histopathologic appearance of gelatin-based hemostatic
      agents, Surgiflo, Gelfoam, and Floseal, which are used by ophthalmic plastic
      surgeons, and which may incidentally be found as foreign materials in
      histopathologic tissue samples. METHODS: Histopathologic analysis was performed
      with hematoxylin-eosin, periodic acid-Schiff, Masson trichrome, and elastin
      staining on tissue samples in which gelatin-based agents were found. To better
      characterize these materials, similar analyses were performed on in vitro samples
      of commonly used gelatin-based hemostatic agents. RESULTS: Surgiflo and Gelfoam
      are composed of small stellate pieces of gelatin with a smooth, homogeneous
      quality. In tissues, they are faintly positive with periodic acid-Schiff
      staining, amphophilic with Masson trichrome staining, and ink-black with elastin
      staining. Floseal has a distinctly different morphology of large rectangular
      sheets, yet almost identical in vitro staining properties. DISCUSSION: While the
      morphology of the gelatin-based hemostatic agents is consistent under various
      conditions, the staining properties of these materials differ based on whether
      they have been in contact with human tissue. CONCLUSIONS: Gelatin-derived
      hemostatic agents are best identified based on their morphologic characteristics.
      Elastin staining highlights these materials prominently within tissue samples and
      may be helpful in distinguishing them from other foreign materials.

PMID- 29334540
TI  - Predictors of Success Following Muller's Muscle-Conjunctival Resection.
AB  - PURPOSE: This study aims to describe Muller's muscle-conjunctival resection
      surgery in terms of outcomes and potential factors that may predict final
      positions. METHODS: This cross-sectional cohort study included patients
      undergoing Muller's muscle-conjunctival resection surgery for involutional ptosis
      over a 15-year period. Success was defined in 2 ways: 1) final marginal reflex
      distance 1 (MRD1) >=2.5 mm (MRD1 success) and 2) final difference in MRD1 <=1 mm
      between eyelids (symmetry success). Percentages of patients achieving both
      outcomes were calculated. Predictors of outcome were assessed using bivariate
      analysis and multivariate models. RESULTS: The final sample included 315 eyes in
      192 patients. The mean age (standard deviation) was 67.9 (11.9) years, and 60.0%
      were female. MRD1 >=2.5 mm was achieved in 65.7% of the sample. Symmetry within 1
      mm was achieved in 82.9% of the sample. Significant (p < 0.05) predictors of MRD1
      success were female sex, concurrent lower eyelid blepharoplasty, and higher
      preoperative MRD1 in bivariate analysis; preoperative MRD1 and female sex in the
      multivariate model; and preoperative MRD1 in the a priori model. Significant (p <
      0.05) predictors of symmetry success were female sex, previous lower eyelid
      blepharoplasty, concurrent lateral canthoplasty, preoperative symmetry, and older
      age in bivariate analysis; only female sex in the multivariate model. DISCUSSION:
      Muller's muscle-conjunctival resection is effective for elevating the eyelid in
      ptosis and may be more effective for achieving symmetry than absolute elevation
      over 2.5 mm. The results remain difficult to predict based clinical, surgical, or
      demographic factors.

PMID- 29334541
TI  - A Novel Technique for Measuring Eyelid Force.
AB  - PURPOSE: We present a novel technique to directly measure the eyelid upward force
      generation. This technique can be used during routine clinical examination using
      an inexpensive, portable force gauge. METHODS: This prospective case series was
      conducted January to June 2015 in an ophthalmology clinic affiliated with a
      tertiary care medical center. A convenience sample of 42 patients (40-90 years of
      age) without known eyelid pathology participated. The eyelid upward net force
      generated was measured directly using a handheld dynamometer noninvasively
      attached to the upper eyelid. Comparison of the eyelid-brow upward force
      generated with eyelid upward net force generated allowed us to assess the
      contribution of levator and frontalis muscles to the force generated during
      upgaze. Data were evaluated with relation to gender and age. RESULTS: Upper
      eyelid force generated was 53.3 g OD and 53.9 g OS; the generated force during
      frontalis muscle fixation was 38.4 g OD and 41.1 g OS. The levator and frontalis
      muscles showed a 3:1 ratio respectively in their contribution to the force
      generated during upgaze. Although no statistically significant differences were
      seen between eyes, gender, or within age groups, younger patients showed
      increased generating force which is attributed to the levator muscle. Interclass
      correlation coefficient showed virtually no correlation between clinical eyelid
      assessments and direct muscle force measurement. Reliability for repeated direct
      force measurements by the same physician was strong, with interclass correlation
      coefficient 0.951 to 0.969. No adverse events occurred. CONCLUSIONS: We describe
      a simple, reliable, inexpensive, new method for assessing upper eyelid upward
      force generation. Because the levator muscle serves as the primary contributor to
      eyelid elevation, this directly measurable eyelid assessment may help to increase
      understanding of its functional contribution and assessment when assessing eyelid
      pathologies.

PMID- 29334542
TI  - Medial Buttressing in Orbital Blowout Fractures.
AB  - PURPOSE: To study whether ethmoidectomy predisposes the orbit to medial wall
      fracture with lesser trauma. METHODS: An interventional cadaver study of 5 heads
      (10 orbits); the left or right orbit was randomized to undergo endoscopic
      complete ethmoidectomy with the fellow orbit as control. Fractures were induced
      with direct globe trauma, and heads underwent CT scanning. Energy to induce
      fracture, peak orbital pressure at time of fracture, fracture pattern, and volume
      of herniated tissue were measured and analyzed. RESULTS: Fractures were induced
      in both orbits of all cadavers. Experimental orbits after ethmoidectomy sustained
      orbital fracture at less energy required (2.14 +/- 0.66 vs. 3.10 +/- 0.19 J, mean
      difference: -0.96 +/- 0.33 J, p < 0.05). Similarly, peak orbital pressure was
      lower for ethmoidectomized orbits than for controls (11.8 +/- 8.42 vs. 28.4 +/-
      13.2 mm Hg, mean difference: -16.5 +/- 6.9 mm Hg, p < 0.05). Orbits after
      ethmoidectomy were more likely to sustain medial wall involvement in fracture
      (100%) compared with controls (20%, p < 0.05) and pure medial wall fracture (80%)
      compared with controls (0%, p < 0.05). Overall volume of herniated orbital
      contents was not significantly different between groups (p = 0.25); volume of
      herniated tissue from the medial wall only was significantly greater in orbits
      after ethmoidectomy (mean difference: 1.01 +/- -0.39 cm, p < 0.05). CONCLUSION:
      Endoscopic ethmoidectomy in fresh cadavers reduces impact energy necessary to
      induce orbital fracture and increases the prevalence of medial wall involvement.
      Clinicians may wish to counsel patients undergoing endoscopic sinus surgery about
      these relative risks.

PMID- 29334543
TI  - Seminoma Metastatic to the Orbit.
AB  - PURPOSE: Seminomas are solid tumors in young men, but which rarely metastasize to
      the orbit. The authors review the known literature on seminoma metastatic to the
      orbit, and describe an additional case in a 33-year-old man. METHODS: A
      literature search was performed on the MEDLINE database using keywords
      "seminoma," "testicular germ-cell tumors," "testicular cancer," "testicular
      neoplasm," "orbital metastasis," and "germ-cell neoplasms." RESULTS: Malignant
      neoplasms of the testis account for only 1% of cancers in men. None-the-less,
      testicular germ cell seminoma is the most common solid tumor found in young men
      between the ages of 15 and 39. Only seven previous cases have been mentioned in
      the literature. The pathogenesis remains unclear although genetic, environmental,
      and maternal factors may play a role. The number of cases is too few to determine
      the best treatment options, but surgical excision and adjunctive orbital
      radiotherapy appear to be most appropriate. CONCLUSIONS: Although metastases to
      the orbit are rare, seminoma should be considered in the differential diagnosis
      of all young men with proptosis.

PMID- 29334544
TI  - Blood biomarkers of expressed and inducible HIV-1.
AB  - OBJECTIVE: To define the relationships between molecular measures of viral
      persistence in blood (i.e., plasma viremia, cellular HIV-1 DNA, and mRNA) and
      expressed or inducible virus from resting CD4 T cells of individuals on
      suppressive antiretroviral therapy. DESIGN: We compared molecular measurements of
      HIV-1 in plasma and in uncultured peripheral blood mononuclear cells (PBMCs) to
      the levels of virions produced by either unstimulated or phorbol myristate
      acetate and ionomycin (PMA/iono)-stimulated PBMC or resting CD4 T cells from 21
      donors on suppressive antiretroviral therapy. RESULTS: We found that unstimulated
      virion release from cultured resting CD4 T cells was positively correlated with
      the levels of plasma viremia in vivo (Spearman rho = 0.67, P = 0.0017). We also
      found that levels of both cellular HIV-1 DNA and unspliced HIV-1 mRNA per million
      uncultured PBMC were positively correlated with the levels of inducible virion
      release from both PMA/iono-stimulated PBMC (total HIV-1 DNA: rho = 0.64, P =
      0.0017; unspliced HIV-1 RNA: rho = 0.77, P < 0.001) and PMA/iono-stimulated
      resting CD4 T cells (total HIV-1 DNA: rho = 0.75, P < 0.001; unspliced HIV-1 RNA:
      rho = 0.75, P < 0.001). CONCLUSION: These results show for the first time that
      there are strong associations between in-vivo measures of HIV-1 persistence and
      ex-vivo measures of spontaneous and inducible virus production from cultured PBMC
      and resting CD4 T cells. Findings from this study provide insight into the
      biology of HIV-1 persistence and suggest methods to guide the evaluation of
      clinical strategies to reduce the size of the viral reservoir.

PMID- 29334545
TI  - Bacterial vaginosis modifies the association between hormonal contraception and
      HIV acquisition.
AB  - OBJECTIVE: To examine bacterial vaginosis as an effect modifier for the
      association between hormonal contraception and incident HIV infection. DESIGN:
      Serodiscordant couples enrolled in an open longitudinal cohort in Lusaka, Zambia
      from 1994 to 2012. This analysis was restricted to couples with an HIV-positive
      man enrolled between1994 and 2002 when a quarterly genital tract examination and
      HIV testing was performed. METHODS: Multivariate Cox models evaluated the
      association between contraceptive method and HIV-acquisition, stratified by time
      varying bacterial vaginosis status. RESULTS: Among 564 couples contributing
      1137.2 couple-years of observation, bacterial vaginosis was detected at 15.5% of
      study visits. Twenty-two of 106 seroconversions occurred during intervals after
      bacterial vaginosis was detected [12 on no method/nonhormonal method (nonhormonal
      contraception), two on injectables, eight on oral contraceptive pills (OCPs)].
      Unadjusted seroincidence rates per 100 couple-years for nonhormonal
      contraception, injectable, and OCP users, respectively, during intervals with
      bacterial vaginosis were 8.3, 20.8, and 31.0 and during intervals without
      bacterial vaginosis were 8.2, 9.7, and 12.3. In the bacterial vaginosis-positive
      model, there was a significant increase in incident HIV among those using
      injectables (adjusted hazard ratio, aHR 6.55, 95% CI 1.14-37.77) and OCPs (aHR
      5.20, 95% CI 1.68-16.06) compared with nonhormonal contraception. Hormonal
      contraception did not increase the hazard of HIV acquisition in bacterial
      vaginosis-negative models. These findings persisted in sensitivity analyses
      whenever all covariates from the nonstratified model previously published were
      included, whenever other genital tract findings were excluded from the model and
      with the addition of condom-less sex and sperm on wet-prep. CONCLUSION: Future
      research should consider a potential interaction with bacterial vaginosis
      whenever evaluating the impact of hormonal contraception on HIV acquisition.

PMID- 29334546
TI  - Impact of early antiretroviral therapy eligibility on HIV acquisition: household
      level evidence from rural South Africa.
AB  - OBJECTIVES: We investigate the effect of immediate antiretroviral therapy (ART)
      eligibility on HIV incidence among HIV-uninfected household members. DESIGN:
      Regression discontinuity study arising from a population-based cohort. METHODS:
      Household members of patients seeking care at the Hlabisa HIV Treatment and Care
      Programme in rural KwaZulu-Natal South Africa between January 2007 and August
      2011 with CD4 cell counts up to 350 cells/MUl were eligible for inclusion if they
      had at least two HIV tests and were HIV-uninfected at the time the index patient
      linked to care (N = 4115). Regression discontinuity was used to assess the
      intention-to-treat effect of immediate versus delayed ART eligibility on HIV
      incidence among household members. Exploiting the CD4 cell count-based threshold
      rule for ART initiation (CD4 < 200 cells/MUl until August 2011), we used Cox
      proportional hazards models to compare outcomes for household members of patients
      who presented for care with CD4 cell counts just above versus just below the ART
      initiation threshold. RESULTS: Characteristics of household members of index
      patients initiating HIV care were balanced between those with an index patient
      immediately eligible for ART (N = 2489) versus delayed for ART (N = 1626). There
      were 337 incident HIV infections among household members, corresponding to an HIV
      incidence of 2.4 infections per 100 person-years (95% confidence interval 2.5
      3.1). Immediate eligibility for treatment reduced HIV incidence in households by
      47% in our optimal estimate (hazard ratio = 0.53, 95% confidence interval 0.30
      0.96), and by 32-60% in alternate specifications of the model. CONCLUSION:
      Immediate eligibility of ART led to substantial reductions in household-level HIV
      incidence.

PMID- 29334547
TI  - Quality of life improvement in resource-limited settings after one year of second
      line antiretroviral therapy use among adult men and women.
AB  - OBJECTIVE: We evaluated improvement of quality of life (QoL) after 1 year of
      second-line antiretroviral therapy (ART) use in resource-limited settings (RLS)
      among adult men and women, comparing two randomized treatment arms. DESIGN: The
      AIDS Clinical Trial Group A5273 was a randomized clinical trial of second-line
      ART comparing lopinavir/ritonavir (LPV/r) + raltegravir with LPV/r +
      nucleos(t)ide reverse transcriptase inhibitors (NRTIs) in participants failing a
      non-NRTI-containing regimen at 15 sites in nine RLS. Participants completed the
      AIDS Clinical Trial Group short-form-21 which has eight QoL domains with a
      standard score ranging from 0 (worst) to 100 (best). METHODS: Differences in QoL
      by randomized arm, as well as by demographic and clinical variables, were
      evaluated by regression models for baseline and week 48 QoL scores fitted using
      the generalized estimating equations method. RESULTS: A total of 512 individuals
      (49% men, median age 39 years) were included. A total of 512 and 492 participants
      had QoL assessments at baseline and week 48, respectively. QoL improved
      significantly from baseline to week 48 (P < 0.001 for all domains). There was no
      significant difference between treatment arms for any domain. Individuals with
      higher viral load and lower CD4 cell count at baseline had lower mean QoL at
      baseline but larger improvements such that mean QoL was similar at week 48.
      CONCLUSION: Improvements in QoL were similar after starting second-line ART of
      LPV/r combined with either raltegravir or NRTIs in RLS. QoL scores at baseline
      were lower among participants with worse disease status prior to starting second
      line, but after 1 year similar QoL scores were achieved.

PMID- 29334548
TI  - Plasma and intracellular pharmacokinetics of tenofovir in patients switched from
      tenofovir disoproxil fumarate to tenofovir alafenamide.
AB  - OBJECTIVES: The aim of the study was to compare the intraindividual plasma and
      intracellular peripheral blood mononuclear cell (PBMC) pharmacokinetics of
      tenofovir (TFV) and its intracellular metabolite, TFV-diphosphate (TFV-DP) in
      patients switched from a fixed-dose combination (FDC) tablet of TFV disoproxil
      fumarate (TDF)/emtricitabine (FTC)/elvitegravir (EVG)/cobicistat (COBI) to a FDC
      containing TFV alafenamide (TAF)/FTC/EVG/COBI. DESIGN: A single-arm, prospective,
      nonrandomized, cross-over, pharmacokinetic study in patients receiving a TDF
      containing regimen (TDF 300 mg/FTC 200 mg/EVG 150 mg/COBI 150 mg) switched to a
      TAF-containing FDC regimen (TAF 10 mg/FTC 200 mg/EVG 150 mg/COBI 150 mg).
      METHODS: Single, sparse plasma and PBMC samples were collected during TDF therapy
      and 4-8 weeks post-switch to the TAF-containing regimen. Plasma TFV and cell
      associated TFV-DP concentrations were determined with validated liquid
      chromatography tandem mass spectrometry methods. PBMC cell enumeration was
      performed by quantification of RNaseP (RPP30) gene copy numbers using a highly
      sensitive droplet digital PCR assay. Plasma and PBMC pharmacokinetics were
      summarized as geometric mean and compared as a geometric mean ratio with a
      Wilcoxon signed-rank test. RESULTS: In 30 participants with evaluable data, TFV
      plasma concentrations decreased 90% [TDF: 99.98 (2.24) ng/ml vs. TAF: 10.2 (1.6)
      ng/ml, P < 0.001] after the switch while cell-associated TFV-DP increased 2.41
      fold [TAF: 834.7 (2.49) vs. TDF: 346.85 (3.75) fmol/10 cells, P = 0.004].
      CONCLUSION: Intraindividually, plasma TFV concentrations significantly decreased
      while cell associated TFV-DP concentrations significantly increased after
      switching from a TDF to a TAF-containing antiretroviral therapy regimen.

PMID- 29334549
TI  - Cost-effectiveness of alternative strategies for provision of HIV preexposure
      prophylaxis for people who inject drugs.
AB  - BACKGROUND: Oral HIV preexposure prophylaxis (PrEP) has been recommended as a
      means of HIV prevention among people who inject drugs (PWIDs) but, at current
      prices, is unlikely to be cost-effective for all PWID. OBJECTIVE: To determine
      the cost-effectiveness of alternative strategies for enrolling PWID in PrEP.
      DESIGN: Dynamic network model that captures HIV transmission and progression
      among PWID in a representative US urban center. OUTCOME MEASURES: HIV infections
      averted, discounted costs and quality-adjusted life-years (QALYs), and
      incremental cost-effectiveness ratios. INTERVENTION: We assume 25% PrEP coverage
      and investigate four strategies: first, random PWID are enrolled (Unselected
      Enrollment); second, individuals are randomly selected and enrolled together with
      their partners (Enroll Partners); third, individuals with the highest number of
      sexual and needle-sharing partnerships are enrolled (Most Partners); fourth,
      individuals with the greatest number of infected partners are enrolled (Most
      Positive Partners). RESULTS: PrEP can achieve significant health benefits:
      compared with the status quo of no PrEP, the strategies gain 1114 QALYs
      (Unselected Enrollment), 2194 QALYs (Enroll Partners), 2481 QALYs (Most
      Partners), and 3046 QALYs (Most Positive Partners) over 20 years in a population
      of approximately 8500 people. The incremental cost-effectiveness ratio of each
      strategy compared with the status quo (cost per QALY gained) is $272 000
      (Unselected Enrollment), $158 000 (Enroll Partners), $124 000 (Most Partners),
      and $101 000 (Most Positive Partners). All strategies except Unselected
      Enrollment are cost-effective according to WHO criteria. CONCLUSION: Selection of
      high-risk PWID for PrEP can improve the cost-effectiveness of PrEP for PWID.

PMID- 29334551
TI  - Rapid decline of HIV-1 DNA and RNA in infants starting very early antiretroviral
      therapy may pose a diagnostic challenge.
AB  - OBJECTIVE: Birth diagnosis of HIV-1 infection offers an ideal opportunity for
      early antiretroviral therapy (ART) to limit HIV-1 reservoir size and limit
      disease progression. Although data on cellular HIV-1 DNA decay exist for children
      commencing treatment from 2 to 3 months of age, data are lacking for starting
      shortly after birth. DESIGN: We studied infants who initiated ART within 8 days
      after birth to assess HIV-1 DNA levels longitudinally. METHODS: Children were
      recruited from public health clinics in Cape Town where birth diagnosis of HIV-1
      coupled with early ART initiation occurred. Total cellular HIV-1 DNA levels were
      determined using a sensitive quantitative PCR targeting a conserved region in
      integrase. RESULTS: Of 11 infants diagnosed and beginning ART within 8 days of
      birth with detectable pre-ART HIV-1 DNA, three subsequently had undetectable HIV
      1 DNA after 6 days, 3 months and 4 months on treatment, respectively. In seven
      who had virologic suppression (defined as a continuous downward trend in plasma
      HIV-1 RNA, and <100 copies/ml after 6 months) total HIV-1 DNA continued to decay
      over 12 months [mean half-life of 64.8 days (95% confidence interval: 47.9
      105.7)]. CONCLUSION: In infants initiated on ART within 8 days of life the
      combination of maternal ART, and early ART for prophylaxis and treatment
      contribute to rapid decline of HIV-1 infected cells to low or undetectable
      levels. However, rapid decline of HIV-1 RNA and DNA may complicate definitive
      diagnosis when confirmatory testing is delayed.

PMID- 29334553
TI  - Post-treatment controllers after treatment interruption in chronically HIV
      infected patients.
AB  - OBJECTIVE: Control HIV replication requires continuous combined antiretroviral
      therapy (cART) as discontinuation of cART results in a rapid viral rebound.
      However, a few individuals exist who took cART for several years and did not show
      the expected viral rebound after treatment cessation. Most post-treatment
      controllers (PTCs) are early treated individuals. We report three cases who
      started cART during chronic infection. DESIGN: Patients were treated and
      monitored according to Italian guidelines. For the description of cases, the
      percentage of CD8CD38HLA*DR cells, CD8CD38HLA*DR cells, major histocompatibility
      complex genotyping, total HIV-DNA and plasma levels of anti-retroviral (ARV)
      drugs were performed. RESULTS: Patients started therapy during chronic infection.
      Patient 26636 started her first ARV drug two years after diagnosis and patients
      93016 and 50293 started cART with high viral loads and low CD4 cell counts. Time
      without cART was 13, 11 and 1.5 years, respectively. None presented any of the
      protective class I HLA alleles and patient 93016 has the HLA-B*35 allele that
      appears to be enriched in PTCs. Patients 93016 and 50293 had very low levels of
      CD8CD38HLA*DR cells (<5%) much lower than those of patient 26636 (27%). T-cell
      associated HIV-DNA was 3.78, 3.48 and 3.13 log copies/10 CD4, respectively.
      CONCLUSION: Patients like ours may advance our understanding of the
      characteristics for which individuals may be more likely to achieve ART-free
      remissions. Furthermore, our patients are among the few so far described who
      started cART during chronic infection extending the hope that a functional cure
      is possible even in this setting.

PMID- 29334554
TI  - The Systemic-Immune-Inflammation Index Independently Predicts Survival and
      Recurrence in Resectable Pancreatic Cancer and its Prognostic Value Depends on
      Bilirubin Levels: A Retrospective Multicenter Cohort Study.
AB  - OBJECTIVE: Our aim was to determine the prognostic significance of the systemic
      immune-inflammation index (SIII) in patients with resectable pancreatic cancer,
      using cancer-specific survival as the primary outcome. BACKGROUND: Pancreatic
      cancer is associated with a dysfunctional immune system and poor prognosis. We
      examined the prognostic significance of the SIII in patients with resectable
      pancreatic ductal adenocarcinoma (PDAC) and the effects of bilirubin on this
      index. METHODS: We retrospectively assessed all pancreatic resections performed
      between 2004 and 2015 at 4 tertiary referral centers to identify pathologically
      confirmed PDAC patients. Baseline clinicopathologic characteristics, preoperative
      laboratory values such as absolute neutrophil, lymphocyte, and platelet counts, C
      reactive protein, albumin, bilirubin, and CA19-9 levels, and also follow-up
      information, were collected. The associations of the calculated inflammatory
      indices with outcome were both internally and externally validated. RESULTS: In
      all, 590 patients with resectable PDAC were included. The discovery and
      validation cohort included 170 and 420 patients, respectively. SIII >900 [hazard
      ratio (HR) 2.32, 95% confidence interval (CI) 1.55-3.48], lymph node ratio (HR
      3.75, 95% CI 2.08-6.76), and CA19.9 >200 kU/L (HR 1.62, 95% CI 1.07-2.46) were
      identified as independent predictors of cancer-specific survival. Separate model
      analysis confirmed that preoperative SIII contributed significantly to
      prognostication. However, SIII appeared to lose its prognostic significance in
      patients with bilirubin levels above 200 MUmol/L. CONCLUSIONS: SIII is an
      independent predictor of cancer-specific survival and recurrence in patients with
      resectable PDAC. SIII may lose its prognostic significance in patients with high
      bilirubin levels. Properly designed prospective studies are needed to further
      confirm this hypothesis.

PMID- 29334550
TI  - Chronic hepatitis C virus infection and subsequent HIV viral load among women
      with HIV initiating antiretroviral therapy.
AB  - OBJECTIVES: One in four persons living with HIV is coinfected with hepatitis C
      virus (HCV). Biological and behavioral mechanisms may increase HIV viral load
      among coinfected persons. Therefore, we estimated the longitudinal effect of
      chronic HCV on HIV suppression after ART initiation among women with HIV (WWH).
      DESIGN: HIV RNA was measured every 6 months among 441 WWH in the Women's
      Interagency HIV Study who initiated ART from 2000 to 2015. METHODS: Log-binomial
      regression models were used to compare the proportion of study visits with
      detectable HIV RNA between women with and without chronic HCV. Robust sandwich
      variance estimators accounted for within-person correlation induced by repeated
      HIV RNA measurements during follow-up. We controlled for confounding and
      selection bias (because of loss to follow-up and death) using inverse probability
      of-exposure-and-censoring weights. RESULTS: One hundred and fourteen women (25%)
      had chronic HCV before ART initiation. Overall, the proportion of visits with
      detectable HIV RNA was similar among women with and without chronic HCV [relative
      risk (RR) 1.19 (95% CI 0.72, 1.95)]. Six months after ART initiation, the
      proportion of visits with detectable HIV RNA among women with chronic HCV was
      1.88 (95% CI 1.41-2.51) times that among women without HCV, at 2 years, the ratio
      was 1.60 (95% CI 1.17-2.19), and by 6 years there was no difference (1.03; 95% CI
      0.60-1.79). CONCLUSION: Chronic HCV may negatively impact early HIV viral
      response to ART. These findings reaffirm the need to test persons with HIV for
      HCV infection, and increase engagement in HIV care and access to HCV treatment
      among persons with HIV/HCV coinfection.

PMID- 29334555
TI  - Multi-institutional Analysis of Recurrence and Survival After Neoadjuvant
      Chemoradiotherapy of Esophageal Cancer: Impact of Histology on Recurrence
      Patterns and Outcomes.
AB  - OBJECTIVE: To determine the impact of histology on pathologic response, survival
      outcomes, and recurrence patterns in patients with esophageal cancer (EC) who
      received neoadjuvant chemoradiotherapy (CRT). SUMMARY OF BACKGROUND DATA: There
      is a paucity of data regarding comparative outcomes after neoadjuvant CRT between
      esophageal squamous cell carcinoma (SCC) and adenocarcinoma. METHODS: Between
      2002 and 2015, 895 EC patients who underwent neoadjuvant CRT followed by
      esophagectomy at 3 academic institutions were retrospectively reviewed, including
      207 patients with SCC (23.1%) and 688 patients with adenocarcinoma (76.9%).
      Pathologic response, survival, recurrence pattern, and potential prognostic
      factors were compared. RESULTS: Pathologic complete response (pCR) rate was
      significantly higher for SCC compared with adenocarcinoma (44.9% vs 25.9%, P <
      0.001). After a median follow-up of 52.9 months, 71 patients (34.3%) with SCC
      versus 297 patients (43.2%) with adenocarcinoma had recurrent disease (P =
      0.023). For patients who achieved a pCR, no significant differences were found in
      recurrence pattern, sites, or survival end-points between the 2 histology groups.
      For non-pCR patients, the SCC group demonstrated significantly higher regional
      and supraclavicular recurrence rates but a lower hematogenous metastasis rate
      than adenocarcinoma patients, whereas the adenocarcinoma patients had a more
      favorable locoregional failure-free survival (P = 0.005) and worse distant
      metastasis-free survival (P = 0.024). No differences were found in overall
      survival (P = 0.772) or recurrence-free survival (P = 0.696) between groups.
      CONCLUSIONS: SCC was associated with a significantly higher pCR rate than
      adenocarcinoma. Recurrence pattern and survival outcomes were significantly
      different between the 2 histology subtypes in non-pCR patients.

PMID- 29334556
TI  - Decoding Grade B Pancreatic Fistula: A Clinical and Economical Analysis and
      Subclassification Proposal.
AB  - OBJECTIVE: The aim of this study was to describe characteristics and management
      approaches for grade B pancreatic fistula (B-POPF) and investigate whether it
      segregates into distinct subclasses. BACKGROUND: The 2016 ISGPS refined
      definition of B-POPF is predicated on various postoperative management
      approaches, ranging from prolonged drainage to interventional procedures, but the
      spectrum of clinical severity within this entity is yet undefined. METHODS:
      Pancreatectomies performed at 2 institutions from 2007 to 2016 were reviewed to
      identify B-POPFs and their treatment strategies. Subclassification of B-POPFs
      into 3 classes was modeled after the Fistula Accordion Severity Grading System
      (B1: prolonged drainage only; B2: pharmacologic management; B3: interventional
      procedures). Clinical and economic outcomes, unique from the ISGPS definition
      qualifiers, were analyzed across subclasses. RESULTS: B-POPF developed in 320 of
      1949 patients (16.4%), and commonly required antibiotics (70.3%), prolonged
      drainage (67.8%), and enteral/parenteral nutrition (54.7%). Percutaneous drainage
      occurred in 79 patients (24.7%), always in combination with other strategies.
      Management of B-POPFs was widely heterogeneous with a median of 2
      approaches/patient (range 1 to 6) and 38 various strategy combinations used.
      Subclasses B1-3 comprised 19.1%, 52.2%, and 28.8% of B-POPFs, respectively, and
      were associated with progressively worse clinical and economic outcomes. These
      results were confirmed by multivariable analysis adjusted for clinical and
      operative factors. Notably, distribution of the B-POPF subclasses was influenced
      by institution and type of resection (P < 0.001), while clinical/demographic
      predictors proved elusive. CONCLUSION: B-POPF is a heterogeneous entity, where 3
      distinct subclasses with increasing clinical and economic burden can be
      identified. This classification framework has potential implications for accurate
      reporting, comparative research, and performance evaluation.

PMID- 29334557
TI  - So What's the Chance of This Mesh Causing Me a Problem in the Long Run?

PMID- 29334558
TI  - Comment on: A Propensity Score Matched Analysis of Open Versus Minimally Invasive
      Transthoracic Esophagectomy in the Netherlands.

PMID- 29334559
TI  - Sex Differences in Faculty Rank Among Academic Surgeons in the United States in
      2014.
AB  - OBJECTIVE: The aim of this study was to evaluate sex differences in full
      professorship among a comprehensive, contemporary cohort of US academic surgeons.
      SUMMARY OF BACKGROUND DATA: Previous work demonstrates that women are less likely
      than men to be full professors in academic medicine, and in certain surgical
      subspecialties. Whether sex differences in academic rank exist across all
      surgical fields, and after adjustment for confounders, is not known. METHODS: A
      comprehensive list of surgeons with faculty appointments at US medical schools in
      2014 was obtained from Association of American Medical Colleges (AAMC) faculty
      roster and linked to a comprehensive physician database from Doximity, an online
      physician networking website, which contained the following data for all
      physicians: sex, age, years since residency, publication number (total and
      first/last author), clinical trials participation, National Institutes of Health
      grants, and surgical subspecialty. A 20% sample of 2013 Medicare payments for
      care was added to this dataset. Multivariable regression models were used to
      estimate sex differences in full professorship, adjusting for these variables and
      medical school-specific fixed effects. RESULTS: Among 11,549 surgeon faculty at
      US medical schools in 2014, 1692 (14.7%) were women. Women comprised 19.4% of
      assistant professors (1072/5538), 13.8% of associate professors (404/2931), and
      7.0% of full professors (216/3080). After multivariable analysis, women were less
      likely to be full professors than men (adjusted odds ratio: 0.76, 95% confidence
      interval: 0.6-0.9). CONCLUSION: Among surgical faculty at US medical schools in
      2014, women were less likely than men to be full professors after adjustment for
      multiple factors known to impact faculty rank.

PMID- 29334560
TI  - Proposed Modification of the 8th Edition of the AJCC Staging System for
      Pancreatic Ductal Adenocarcinoma.
AB  - OBJECTIVE: The aim of this study was to improve the 8th edition (8th) of the
      American Joint Committee on Cancer (AJCC) staging system for pancreatic ductal
      adenocarcinoma (PDAC). BACKGROUND: The new 8th AJCC staging system for PDAC was
      released in October, 2016, and will be applied in clinical practice in 2018.
      METHODS: Two large cohorts were included in this analysis. One consisted of
      45,856 PDAC patients in the Surveillance, Epidemiology, and End Results (SEER)
      database (2004-2014), and the other consisted of 3166 PDAC patients in the Fudan
      University Shanghai Cancer Center (FUSCC) database (2005-2015). RESULTS: Using
      the 8th AJCC staging system, the median overall survival of the patients in the
      same stage varied widely among the different substages. We proposed a modified
      staging system based on median OS in which we maintained the T, N, and M
      definitions, but regrouped the substages. In the SEER cohort, the concordance
      index was higher for local disease with the modified staging system [0.637; 95%
      confidence interval (CI) 0.631-0.642] than with the 8th AJCC staging system
      (0.620, 95% CI 0.615-0.626). Similar findings were also observed in the FUSCC
      cohort. In addition, we verified the reliability of the modified staging system
      in an analysis of patients with different examined lymph node counts (>=15 or 1
      14). CONCLUSIONS: The modified 8th AJCC staging system for PDAC proposed in this
      study provides improvements and may be evaluated for potential adoption in the
      next edition.

PMID- 29334561
TI  - Preoperative 18F-FDG PET/CT in Pheochromocytomas and Paragangliomas Allows for
      Precision Surgery.
AB  - BACKGROUND: Fluorodeoxyglucose (F-FDG) positron emission tomography/computed
      tomography (PET/CT) imaging is recommended in patients with metastatic
      pheochromocytoma (PC) and paraganglioma (PGL). There are no data on whether
      routine preoperative F-FDG PET/CT in all patients with PC/PGL impacts surgical
      management. OBJECTIVE: The aim of this study was to determine whether routine
      preoperative F-FDG PET/CT imaging affects the surgical management of patients
      with PC/PGLs. METHODS: We analyzed clinical, biochemical, genetic, and anatomic
      imaging data in 93 consecutive patients with PC/PGL who collectively underwent a
      total of 100 operations and who had preoperative F-FDG PET/CT imaging. RESULTS:
      Of 100 operations, preoperative F-FDG PET/CT showed additional lesions compared
      to anatomic imaging in 15 cases. These patients were more likely to undergo an
      open surgical approach (P < 0.05). Presence of genetic mutation, redo operations,
      sex, age, or tumor size had no significant association with finding additional
      lesions on F-FDG PET/CT. CONCLUSIONS: Additional lesions detected on preoperative
      F-FDG-PET/CT imaging have an impact on the surgical approach in patients with
      PC/PGLs. Therefore, surgeons should routinely obtain F-FDG-PET/CT imaging in
      patients with PC/PGL to allow for a more precise surgical intervention.

PMID- 29334563
TI  - Response to the Letter to the Editor by CM den Bakker and DL van Der Peet.

PMID- 29334562
TI  - Is a Pathological Complete Response Following Neoadjuvant Chemoradiation
      Associated With Prolonged Survival in Patients With Pancreatic Cancer?
AB  - OBJECTIVES: To describe the survival outcome of patients with borderline
      resectable or locally advanced pancreatic ductal adenocarcinoma (BR/LA-PDAC) who
      have a pathologic complete response (pCR) following neoadjuvant chemoradiation.
      BACKGROUND: Patients with BR/LA-PDAC are often treated with neoadjuvant
      chemoradiation in an attempt to downstage the tumor. Uncommonly, a pCR may
      result. METHODS: A retrospective review of a prospectively maintained database
      was performed at a single institution. pCR was defined as no viable tumor
      identified in the pancreas or lymph nodes by pathology. A near complete response
      (nCR) was defined as a primary tumor less than 1 cm, without nodal metastasis.
      Overall survival (OS) and disease-free survival (DFS) were reported. RESULTS: One
      hundred eighty-six patients with BR/LA-PDAC underwent neoadjuvant chemoradiation
      and subsequent pancreatectomy. Nineteen patients (10%) had a pCR, 29 (16%) had an
      nCR, and the remaining 138 (74%) had a limited response. Median DFS was 26 months
      in patients with pCR, which was superior to nCR (12 months, P = 0.019) and
      limited response (12 months, P < 0.001). The median OS of nCR (27 months, P =
      0.003) or limited response (26 months, P = 0.001) was less than that of pCR (more
      than 60 months). In multivariable analyses pCR was an independent prognostic
      factor for DFS (HR = 0.45; 0.22-0.93, P = 0.030) and OS (HR=0.41; 0.17-0.97, P =
      0.044). Neoadjuvant FOLFIRINOX (HR=0.47; 0.26-0.87, P = 0.015) and negative lymph
      node status (HR=0.57; 0.36-0.90, P = 0.018) were also associated with improved
      survival. CONCLUSIONS: Patients with BR/LA-PDAC who had a pCR after neoadjuvant
      chemoradiation had a significantly prolonged survival compared with those who had
      nCR or a limited response.

PMID- 29334564
TI  - Validating the Electronic Cardiac Arrest Risk Triage (eCART) Score for Risk
      Stratification of Surgical Inpatients in the Postoperative Setting: Retrospective
      Cohort Study.
AB  - OBJECTIVE: Assess the accuracy of 3 early warning scores for predicting severe
      adverse events in postoperative inpatients. SUMMARY OF BACKGROUND DATA:
      Postoperative clinical deterioration on inpatient hospital services is associated
      with increased morbidity, mortality, and cost. Early warning scores have been
      developed to detect inpatient clinical deterioration and trigger rapid response
      activation, but knowledge regarding the application of early warning scores to
      postoperative inpatients is limited. METHODS: This was a retrospective cohort
      study of adult patients hospitalized on the wards after surgical procedures at an
      urban academic medical center from November, 2008 to January, 2016. The
      accuracies of the Modified Early Warning Score (MEWS), National Early Warning
      Score (NEWS), and the electronic cardiac arrest risk triage (eCART) score were
      compared in predicting severe adverse events (ICU transfer, ward cardiac arrest,
      or ward death) in the postoperative period using the area under the receiver
      operating characteristic curve (AUC). RESULTS: Of the 32,537 patient admissions
      included in the study, 3.8% (n = 1243) experienced a severe adverse outcome after
      the procedure. The accuracy for predicting the composite outcome was highest for
      eCART [AUC 0.79 (95% CI: 0.78-0.81)], followed by NEWS [AUC 0.76 (95% CI: 0.75
      0.78)], and MEWS [AUC 0.75 (95% CI: 0.73-0.76)]. Of the individual vital signs
      and labs, maximum respiratory rate was the most predictive (AUC 0.67) and maximum
      temperature was an inverse predictor (AUC 0.46). CONCLUSION: Early warning scores
      are predictive of severe adverse events in postoperative patients. eCART is
      significantly more accurate in this patient population than both NEWS and MEWS.

PMID- 29334565
TI  - Reversal of Intestinal Failure in Children With Tufting Enteropathy Supported
      With Parenteral Nutrition at Home.
AB  - OBJECTIVES: The aim of the study was to review long-term outcome of intestinal
      epithelial dysplasia (IED)/tufting enteropathy (TE) patients treated with
      parenteral nutrition (PN) at home managed by an intestinal failure (IF)
      rehabilitation service. METHODS: Infants presenting from 1986 to 2010 with IF,
      and TE histology were retrospectively reviewed for up to 30 years. Data collected
      included outcome, presentation, nutrition (parenteral/enteral), country of
      residence, race, EpCAM gene, growth, bone age, and occupation. RESULTS: Thirteen
      patients (6 boys) in Malta and the UK with TE histology were established on home
      PN. Survival was 100% for UK children and 92% overall (1 death aged 13 months).
      Six patients (50% of the surviving 12) weaned off PN. Overall PN requirements
      reduced with increasing age and <7 infusions/week were needed by 10/12, 83% by 10
      years, 6/8, 75% who had reached 15 years, 5/7, 71% who had reached 20, and all 4,
      100% >25 years. Two of 12 cases weaned from PN by 10 years, 1 of 8 by 15 years, 3
      of 7 by 20 years, and 3 of 4 or 75% >25 years. Seven Maltese patients homozygous
      for the same EPCAM gene abnormality had a similar outcome to the other cases.
      Weight, height, bone mineralization, bone age, and insulin-like growth factor-1
      (IGF-1) levels were low, but improved with age. Patients achieved educational
      levels of parents and were employed. CONCLUSIONS: IED cases should have >92%
      chance of long-term survival and >50% chance of enteral autonomy by/in early
      adult life and 75% by 25 years. Even if PN dependent s/he can gain employment.
      Patients with IED managed on PN at home by an IF rehabilitation service should
      avoid intestinal transplant.

PMID- 29334566
TI  - Deficiency of transforming growth factor-beta signaling disrupts memory processes
      in rats.
AB  - Cytokines, in addition to their participation in immune and inflammatory
      processes, play an important role in synaptic plasticity, neoneurogenesis, and
      cognitive functions. In our work, we aimed to clarify the role of the
      transforming growth factor-beta (TGF-beta), which is recognized as a
      multifunctional cytokine, in memory processes. Behavioral experiments were
      carried out in rats using step-through passive avoidance test. The results
      obtained showed that the learning of animals after treatment with SB431542, a
      selective inhibitor of TGF-beta receptors, was impaired, which indicated a
      significant memory deterioration. Nevertheless, the memory of rats remained at
      the control level when TGF-beta and SB431542 were coadministered. Thus, the role
      of TGF-beta in memory retrieval after the passive avoidance test was revealed:
      memory in rats was weakened if the TGF-beta signaling pathway was inhibited
      during learning. Evidently, successful consolidation of at least some types of
      memory requires a normal level of TGF-beta, indicating the modulation of
      cognitive functions by cytokines under normal physiological conditions.

PMID- 29334567
TI  - Pediatric vascular trauma practice patterns and resource availability: A survey
      of American College of Surgeon-designated pediatric trauma centers.
AB  - BACKGROUND: Variation exists in pediatric vascular trauma management. We aim to
      determine practice patterns for vascular trauma management at American College of
      Surgeons verified pediatric trauma centers and evaluate the resources available
      for management of vascular trauma at both freestanding children's hospitals
      (FSCH) and pediatric hospitals within general adult hospitals. METHODS: Pediatric
      surgeons and trauma medical directors at American College of Surgeons designated
      pediatric surgery trauma centers completed a survey designed to evaluate
      anticipated management of traumatic arterial injuries and resource availability.
      Hospital setting comparisons were made using Fisher exact tests and t tests.
      Binomial tests were used to compare pediatric and vascular surgeons' responses to
      clinical vignettes. p Values of 0.05 or less were significant. RESULTS: One
      hundred seventy-six (42%) of 414 pediatric surgeons participated. Vascular
      surgeons are more likely to operatively manage vascular trauma at all anatomic
      sites except subclavian artery when compared to pediatric surgeons, regardless of
      hospital setting (p <0.001). Forty-eight percent of the pediatric trauma medical
      directors completed their portion of the survey. At FSCHs, 36% did not have a
      fellowship-trained vascular surgeon on-call schedule, 27% did not have
      endovascular capabilities, and 18% did not have a radiology technologist always
      available. CONCLUSION: Vascular surgeons are more likely to manage pediatric
      vascular trauma regardless of hospital setting. However, FSCH have fewer
      resources available to provide optimal care. LEVEL OF EVIDENCE: Care management,
      level IV.

PMID- 29334568
TI  - Goal-directed hemostatic resuscitation for trauma induced coagulopathy:
      Maintaining homeostasis.

PMID- 29334569
TI  - Assessment of prehospital hemorrhage and airway care using a simulation model.
AB  - BACKGROUND: The quality of prehospital care impacts patient outcomes. Military
      efforts have focused on training revision and the creation of high-fidelity
      simulation models to address potentially survivable injuries. We sought to
      investigate the applicability of models emphasizing hemorrhage control and airway
      management to a civilian population. METHODS: Prehospital health care providers
      (PHPs) undergoing their annual training were enrolled. A trauma scenario was
      simulated with two modules: hemorrhage control and airway management. Experienced
      raters used a validated tool to assess performance. Pearson correlation, logistic
      regression, and chi tests were used for analysis. RESULTS: Ninety-five PHPs
      participated with a mean experience of 15.9 +/- 8.3 years, and 7.4% reported past
      military training. The PHPs' overall execution rate of the six hemorrhage control
      measures varied from 38.9% to 88.4%. The median blood loss was 1,700 mL
      (interquartile range, 1,043-2,000), and the mean global rater score was 25.0 +/-
      7.4 (scale, 5-40). There was a significant relationship between PHP profession
      and past military experience to their consideration of blood transfusion and
      tranexamic acid. An inverse relationship between blood loss and global rater
      score was found (r = -0.59, n = 88, p = 1.93 * 10). After simulated direct
      laryngoscope failure in the airway module, 58% of PHPs selected video
      laryngoscopy over placement of a supraglottic airway. Eighty-six percent of
      participants achieved bilateral chest rise in the manikin regardless of
      management method. Participants reported improved comfort with skills after
      simulation. CONCLUSION: Our data reveal marginal performance in hemorrhage
      control regardless of the PHP's prior experience. The majority of PHPs were able
      to secure an advanced airway if direct laryngoscope was unavailable with a
      predisposition for video laryngoscopy over supraglottic airway. Our findings
      support the need for continued training for PHPs highlighting hemorrhage control
      maneuvers and increased familiarity with airway management options. Improved
      participant confidence posttraining gives credence to simulation training. LEVEL
      OF EVIDENCE: Prognostic/epidemiological study, level III.

PMID- 29334570
TI  - The effect of prehospital transport time, injury severity, and blood transfusion
      on survival of US military casualties in Iraq.
AB  - BACKGROUND: Reducing time from injury to care can optimize trauma patient
      outcomes. A previous study of prehospital transport of US military casualties
      during the Afghanistan conflict demonstrated the importance of time and treatment
      capability for combat casualty survival. METHODS: A retrospective descriptive
      analysis was conducted to analyze battlefield data collected on US military
      combat casualties during the Iraq conflict from March 19, 2003, to August 31,
      2010. All casualties were analyzed by mortality outcome (killed in action, died
      of wounds, case fatality rate) and compared with Afghanistan conflict. Detailed
      data for those who underwent prehospital transport were analyzed for effects of
      transport time, injury severity, and blood transfusion on survival. RESULTS: For
      the total population, percent killed in action (16.6% vs. 11.1%), percent died of
      wounds (5.9% vs. 4.3%), and case fatality rate (10.0 vs. 8.6) were higher for
      Iraq versus Afghanistan (p < 0.001). Among 1,692 casualties (mean New Injury
      Severity Score, 22.5; mortality, 17.6%) with detailed data, the injury mechanism
      included 77.7% from explosions and 22.1% from gunshot wounds. For prehospital
      transport, 67.6% of casualties were transported within 60 minutes, and 32.4% of
      casualties were transported in greater than 60 minutes. Although 97.0% of deaths
      occurred in critical casualties (New Injury Severity Score, 25-75), 52.7% of
      critical casualties survived. Critical casualties were transported more rapidly
      (p < 0.01) and more frequently within 60 minutes (p < 0.01) than other
      casualties. Critical casualties had lower mortality when blood was received (p <
      0.01). Among critical casualties, blood transfusion was associated with survival
      irrespective of transport time within or greater than 60 minutes (p < 0.01).
      CONCLUSION: Although data were limited, early blood transfusion was associated
      with battlefield survival in Iraq as it was in Afghanistan. LEVEL OF EVIDENCE:
      Performance improvement and epidemiological, level IV.

PMID- 29334571
TI  - Use of French lyophilized plasma transfusion in severe trauma patients is
      associated with an early plasma transfusion and early transfusion ratio
      improvement.
AB  - BACKGROUND: Early transfusion of high ratio of fresh frozen plasma (FFP) and red
      blood cells (RBC) is associated with mortality reduction. However, time to reach
      high ratio is limited by the need to thaw the FFP. French lyophilized plasma
      (FLYP) used by French army and available in military teaching hospital does not
      need to be thawed and is immediately available. We hypothesize that the use of
      FLYP may reduce time to reach a plasma/RBC ratio of 1:1. METHODS: A retrospective
      study performed in a Level 1 trauma center between January 2012 and December
      2015. Severe trauma patients who received 2 U of RBC in the emergency room were
      included and assigned to two groups according to first plasma transfused: FLYP
      group and FFP group. RESULTS: Forty-three severe trauma patients in the FLYP
      group and 29 in the FFP group were included. The time until first plasma
      transfusion was shorter in the FLYP group than in the FFP group, respectively 15
      min (10-25) versus 95 min (70-145) (p < 0.0001). Time until a 1:1 ratio was
      shorter in the FLYP group than in the FFP group. There were significantly fewer
      cases of massive transfusion in the FLYP group than in the FFP group with
      respectively 7% vs. 45% (p < 0.0001). CONCLUSION: The use of FLYP provided
      significantly faster plasma transfusions than the use of FFP as well as a plasma
      and RBC ratio superior to 1:2 that was reached more rapidly in severe trauma
      patients. These results may explain the less frequent need for massive
      transfusion in the patients who received FLYP. These positive results should be
      confirmed by a prospective and randomized evaluation. LEVEL OF EVIDENCE:
      Therapeutic, level IV.

PMID- 29334572
TI  - Assessment of Parasympathetic Activity in Athletes: Comparing Two Different
      Methods-RETRACTION.

PMID- 29334573
TI  - A Fresh Cadaver Study on Indocyanine Green Fluorescence Lymphography: A New Whole
      Body Imaging Technique for Investigating the Superficial Lymphatics.
AB  - BACKGROUND: Identification of the lymphatic system in cadavers is painstaking
      because lymphatic vessels have very thin walls and are transparent. Selection of
      appropriate contrast agents is a key factor for successfully visualizing the
      lymphatics. In this study, the authors introduce a new imaging technique of
      lymphatic mapping in the whole bodies of fresh cadavers. METHODS: Ten fresh human
      cadavers were used for this study. The authors injected 0.1 ml of indocyanine
      green fluorescence solution subcutaneously at multiple spots along the watershed
      lines between lymphatic territories and hand and foot regions. After the body was
      scanned by the near-infrared camera system, fluorescent tissues were harvested
      and histologic examination was performed under the microscope equipped with the
      infrared camera system to confirm that they were the lymphatics. RESULTS:
      Subcutaneously injected indocyanine green was immediately transported into the
      lymphatic vessels after gentle massage on the injection points. Sweeping massage
      along the lymphatic vessels facilitated indocyanine green transport inside the
      lymphatic vessel to move toward the lymph nodes. The lymphatic system was
      visualized well in the whole body. Histologic examinations confirmed that
      indocyanine green was detected in the lymphatic lumens specifically, even when
      located far from the injected points. CONCLUSIONS: The lymphatic system could be
      visualized in whole-body fresh cadavers, as in living bodies, using indocyanine
      green fluorescence lymphography. Compatibility of indocyanine green lymphography
      would facilitate the use of cadaveric specimens for macroscopic and microscopic
      analyses.

PMID- 29334574
TI  - Improved Long-Term Volume Retention of Stromal Vascular Fraction Gel Grafting
      with Enhanced Angiogenesis and Adipogenesis.
AB  - BACKGROUND: The apoptosis of mature adipocytes after fat grafting can result in
      chronic inflammation, absorption, and fibrosis, leading to unpredictable
      outcomes. Selective elimination of mature adipocytes may result in better
      outcomes and a different underlying retention mode. The authors previously
      developed a mature adipocyte-free product, stromal vascular fraction gel, derived
      from lipoaspirate, which eliminates adipocytes and preserves the stromal vascular
      fraction. This study investigated the retention and regeneration mode of stromal
      vascular fraction gel grafting. METHODS: Nude mice were grafted with human
      derived stromal vascular fraction gel or Coleman fat. Detailed cellular events
      over 3 months were investigated histologically and immunohistochemically.
      RESULTS: The retention rate 90 days after grafting was significantly higher for
      stromal vascular fraction gel grafts than for standard Coleman fat (82 +/- 15
      percent versus 42 +/- 9 percent; p < 0.05). Histologic analysis suggested that,
      unlike Coleman fat grafts, stromal vascular fraction gel grafts did not include
      significant necrotic areas. Moreover, although adipose tissue regeneration was
      found in grafts of both groups, rapid angiogenesis and macrophage infiltration
      were observed at a very early stage after stromal vascular fraction gel grafting.
      The presence of small preadipocytes with multiple intracellular lipid droplets in
      stromal vascular fraction gel grafts on day 3 also suggested very early
      adipogenesis. Although some of the cells in the stromal vascular fraction
      survived in stromal vascular fraction gel grafts, most of the newly formed
      adipose tissue was host-derived. CONCLUSION: Stromal vascular fraction gel has a
      high long-term retention rate and a unique adipose regeneration mode, involving
      prompt inflammation and infiltration of immune cells, stimulating rapid
      angiogenesis and inducing host cell-mediated adipogenesis.

PMID- 29334575
TI  - Measurement of Warping Angle in Human Rib Graft: An Experimental Study.
AB  - BACKGROUND: The purpose of this study was to determine the warping angle of the
      costal cartilage in vivo. METHODS: A nasal framework reconstruction with a rib
      graft was performed in a total of 130 patients. After the cartilage specimens
      were prepared, the remaining grafts were used for study. The angle of warping in
      all grafts was measured at 0, 30, and 60 minutes; after 24 hours; and after 1
      week. Eight subgroups of graft thicknesses from central and peripheral groups,
      determined according to the perichondral distance of the grafts, were evaluated,
      and the warping angles of 48 osteochondral and chondral grafts were measured
      individually. Three-way analysis of variance was used to compare the change in
      warping over time to detect differences in the grafts. RESULTS: Significant
      differences were not observed in the 1- to 3-mm-thick grafts of peripheral and
      central origin before 30 minutes (p > 0.05), although significant differences
      were observed in these groups for all time points after 30 minutes (p < 0.05). In
      central and peripheral grafts thicker than 4 mm, a significant warping angle was
      not observed (p > 0.05). In central origin grafts thinner than 1 mm, significant
      differences were not observed in the warping angle (p > 0.05), although they were
      observed in the same grafts of peripheral origin (p < 0.05). Peripheral origin
      grafts thicker than 1 mm showed warping in the direction of the perichondrium (p
      < 0.05), whereas central origin grafts thinner than 1 mm showed warping angle
      irregularities. CONCLUSION: Interlocking stresses are very important in rib
      grafts when balanced cross-sectional carving occurs from the peripheral to the
      central areas. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

PMID- 29334576
TI  - Cheek Volumization and the Nasolabial Fold.
AB  - BACKGROUND: The impression that cheek filling results in longitudinal shortening
      ("lift") of the skin and elevation of the nasolabial crease or nasolabial fold
      has become common within the facial injection community but remains
      unsubstantiated. METHODS: In this study, 77 patients were evaluated before and
      after injection of the cheeks with a hyaluronic acid filler using a three
      dimensional camera system. RESULTS: A constant pattern of skin expansion away
      from the center of the injection and perpendicular to the surface of the skin was
      observed. A subgroup of 37 patients without differences in their preinjection and
      postinjection facial expression were analyzed by direct comparison and failed to
      demonstrate lateral traction (or "pull") on the intervening skin from the cheek
      injection site to the nasolabial crease. Furthermore, there was no photographic
      difference in the nasolabial fold or nasolabial crease. The only patients who
      demonstrated photographic improvement of the medial face were those who had
      filler placed directly in the transition between the lateral nasolabial fold and
      cheek (nasojugal crease). CONCLUSIONS: Filling the cheek with 3 cc of volume does
      not create traction forces or move the skin between the site of injection and the
      nasolabial crease. It is likely that expanding the nasojugal crease is the direct
      visual cue that leads to perceived improvement in the nasolabial fold.

PMID- 29334577
TI  - Consequences of the F.D.A. Directed Moratorium on Silicone Gel Breast Implants -
      1992-2006.
AB  - The FDA silicone gel breast implant moratorium occurred 25 years ago. The
      immediate and long-term consequences of the moratorium are reviewed and assessed.

PMID- 29334578
TI  - Commentary on Norm Cole's "Moratorium Consequences."

PMID- 29334579
TI  - Implementation of [18F]-labeled amyloid brain PET imaging biomarker in the
      diagnosis of Alzheimer's disease: first-hand experience in Thailand.

PMID- 29334580
TI  - Load-Power Relationship During a Countermovement Jump: A Joint Level Analysis.
AB  - Williams, KJ, Chapman, DW, Phillips, EJ, and Ball, N. Load-power relationship
      during a countermovement jump: A joint level analysis. J Strength Cond Res 32(4):
      955-961, 2018-This study aimed to investigate whether hip, knee, and ankle peak
      power is influenced by the relative load lifted, altering the joint and system
      load-power relationship during a countermovement jump (CMJ). Twenty-three male
      national representative athletes (age: 20.3 +/- 3.1 years, squat 1 repetition
      maximum [1RM]: 133.8 +/- 24.8 kg) completed 3 CMJs at relative barbell loads of
      0, 10, 20, 30, and 40% of an athlete's estimated back squat 1RM. Ground reaction
      force and joint kinematics were captured using a 16 camera motion capture array
      integrated with 2 in-ground triaxial force plates. Hip ((Equation is included in
      full-text article.)= 20%, range 0 > 40%), knee ((Equation is included in full
      text article.)= 0%, 0 > 20%), and ankle ((Equation is included in full-text
      article.)= 40%, 0 > 40%) peak power was maximized at different percentages of
      absolute strength, with an athlete-dependent variation in load-power profiles
      observed across all lower-body joints. A decrease in system (body + barbell mass)
      peak power was significantly (p <= 0.05, r = 0.45) correlated with a reduction in
      knee peak power. Timing of instantaneous system and hip peak power occurred
      significantly closer to toe-off as load increased. The findings highlight that
      the generation and translation of lower-body joint power is influenced by
      external load and athlete-dependent traits. This subsequently alters the load
      power profile at a system level, explaining the broad spectrums of loads reported
      to optimize system power during a CMJ. When training, we recommend that a
      combination of barbell loads based on assorted percentages of the estimated 1RM
      be prescribed to optimize joint and system power during a CMJ.

PMID- 29334581
TI  - Gender- and Muscle-Specific Responses During Fatiguing Exercise.
AB  - Hill, EC, Housh, TJ, Smith, CM, Schmidt, RJ, and Johnson, GO. Gender- and muscle
      specific responses during fatiguing exercise. J Strength Cond Res 32(5): 1471
      1478, 2018-The purpose of the present investigation was to examine potential
      gender-related differences in electromyographic (EMG) and mechanomyographic (MMG)
      responses during submaximal, concentric, isokinetic, forearm flexion muscle
      contractions. Twelve men and 12 women performed concentric peak torque trials
      before (pretest) and after (posttest) a fatiguing exercise bout that consisted of
      50 submaximal (65% of concentric peak torque), concentric, isokinetic (60 degrees
      .s), forearm flexion muscle contractions. Surface EMG and MMG signals were
      simultaneously recorded from the biceps brachii and brachioradialis muscles.
      There was a gender-related difference in the decline in absolute concentric peak
      torque for the men (23.8%) vs. women (18.5%) that was eliminated when covaried
      for differences in pretest concentric peak torque values. During the fatiguing
      exercise bout, EMG amplitude(AMP) increased and EMG mean power frequency (MPF)
      decreased for both genders and muscles. There were, however, muscle- and gender
      specific increases, decreases, and no changes for MMG AMP and MMG MPF. The gender
      related difference for the posttest decline in concentric peak torque was
      associated with differences in muscle strength which may have resulted in greater
      blood flow occlusion in the men than the women. The muscles with the most
      pronounced fatigue-induced neuromuscular responses were the biceps brachii in men
      and the brachioradialis in women. These findings may be related to gender
      differences in the usage patterns of synergistic muscles during a fatiguing task.

PMID- 29334582
TI  - Carbohydrate Mouth Rinsing Does Not Prevent the Decline in Maximal Strength After
      Fatiguing Exercise.
AB  - Black, CD, Schubert, DJ, Szczyglowski, MK, and Wren, JD. Carbohydrate mouth
      rinsing does not prevent the decline in maximal strength after fatiguing
      exercise. J Strength Cond Res 32(9): 2466-2473, 2018-Carbohydrate (CHO) rinsing
      has been shown to attenuate the decline of maximal voluntary contractions (MVCs)
      after fatiguing exercise-perhaps through a central mechanism. This study sought
      to determine the effect of a CHO rinse on MVC, voluntary activation, and
      contractile properties after fatiguing exercise. Thirteen adults participated in
      a double-blind, cross-over study. Maximal voluntary contraction of the dominant
      knee extensors was assessed, and voluntary activation (%VA) was determined using
      twitch interpolation. Participants then held 50% of MVC until volitional fatigue
      followed by a 20-second rinse with a solution of 8% maltodextrin (CHO) or placebo
      (PLA). Maximal voluntary contraction and %VA were reassessed immediately and 5
      minutes after exercise. Maximal voluntary contraction did not differ between the
      CHO and PLA conditions initially (230 +/- 90 vs. 232 +/- 90 N.m; p = 0.69).
      Maximal voluntary contraction declined after exercise (p <= 0.01), but no
      differences were found between the CHO and PLA conditions (p >= 0.59). %VA did
      not differ between conditions (91.9 +/- 2.9% vs. 91.5 +/- 3.8%; p >= 0.11) nor
      did it change after exercise (p = 0.57). Twitch torque, rate of torque
      development, and rate of torque relaxation were reduced after exercise (p <=
      0.05) but were unaffected by CHO rinsing (p > 0.05). Unlike a previous study, a
      CHO rinse did not preserve MVC after fatiguing exercise. This was likely due to a
      lack of central fatigue induced by the exercise protocol (as %VA was unaffected)
      as the CHO rinse is thought to work through a central mechanism.

PMID- 29334583
TI  - Effects of Carnosine (Beta-Alanyl-L-Histidine) in an Experimental Rat Model of
      Acute Kidney Injury Due to Septic Shock.
AB  - BACKGROUND Acute kidney injury (AKI) secondary to sepsis is a major cause of
      morbidity and mortality in the human intensive care unit (ICU). Kidney function
      and the histological findings of AKI were investigated in an experimental rat
      model with sepsis induced by cecal ligation and puncture (CLP) and compared with
      and without treatment with carnosine (beta-alanyl-L-histidine). MATERIAL AND
      METHODS Twenty-four Sprague-Dawley rats were randomly divided into three groups
      consisting eight rats in each: Group 1 - control; Group 2 - septic shock; and
      Group 3 - septic shock treated with carnosine. Femoral vein and artery
      catheterization were applied in all rats. Rats in Group 1 underwent laparotomy
      and catheterization. The other two groups with septic shock underwent laparotomy,
      CLP, catheterization, and bladder cannulation. Rats in Group 3 received an
      intraperitoneal (IP) injection of 250 mg/kg carnosine, 60 min following CLP. Rats
      were monitored for blood pressure, pulse rate, and body temperature to assess
      responses to postoperative sepsis, and 10 mL/kg saline replacement was
      administered. Twenty-four hours following CLP, rats were sacrificed, and blood
      and renal tissue samples were collected. RESULTS Statistically significant
      improvements were observed in kidney function, tissue and serum malondialdehyde
      levels, routine blood values, biochemical indices, and in histopathological
      findings in rats in Group 3 who were treated with carnosine, compared with Group
      2 exposed to septic shock without carnosine treatment. CONCLUSIONS Carnosine
      (beta-alanyl-L-histidine) has been shown to have beneficial effects in reducing
      AKI due to septic shock in a rat model of septicemia.

PMID- 29334584
TI  - In vitro and in vivo metabolite identification of a novel benzimidazole compound
      ZLN005 by LC-MS/MS.
AB  - RATIONALE: A novel benzimidazole compound ZLN005 was previously identified as a
      transcriptional activator of peroxisome proliferator-activated receptor gamma
      coactivator 1alpha (PGC-1alpha) in certain metabolic tissues. Upregulation of PGC
      1alpha by ZLN005 has been shown to have beneficial effect in a diabetic mouse
      model and in a coronary artery disease model in vitro. ZLN005 could also have
      therapeutic potential in neurodegenerative diseases involving down-regulation of
      PGC-1alpha. Given the phenotypic efficacy of ZLN005 in several animal models of
      human disease, its metabolic profile was investigated to guide the development of
      novel therapeutics using ZLN005 as the lead compound. METHODS: ZLN005 was
      incubated with both rat and human liver microsomes and S9 fractions to identify
      in vitro metabolites. Urine from rats dosed with ZLN005 was used to identify in
      vivo metabolites. Extracted metabolites were analyzed by LC-MS/MS using a hybrid
      linear ion trap triple quadrupole mass spectrometer under full scan, enhanced
      product ion scan, neutral loss scan and precursor scan modes. Metabolites in
      plasma and brain of ZLN005-treated rats were also profiled using multiple
      reaction monitoring. RESULTS: Identified in vitro transformations of ZLN005
      include mono- and dihydroxylation, further oxidation to carboxylic acids, and
      mono-O-glucuronide and sulfate conjugation to hydroxy ZLN005 as well as
      glutathione conjugation. Identified in vivo metabolites are mainly glucuronide
      and sulfate conjugates of dihydroxyl, carboxyl, and hydroxy acid of the parent
      compound. The parent compound as well as several major phase I metabolites were
      found in rat plasma and brain. CONCLUSIONS: Using both in vitro and in vivo
      methods, we elucidated the metabolic pathway of ZLN005. Phase I metabolites with
      hydroxylation and carboxylation, as well as phase II metabolites with
      glucuronide, sulfate and glutathione conjugation, were identified.

PMID- 29334585
TI  - Naturally occurring chrysophanol as matrix-assisted laser desorption ionization
      matrix for the analysis of a broad spectrum of analytes.

PMID- 29334587
TI  - Systolic blood pressure as a potential target of sigma-1 receptor agonist
      therapy.

PMID- 29334586
TI  - A Non-Heme Iron Photocatalyst for Light-Driven Aerobic Oxidation of Methanol.
AB  - Non-heme (L)FeIII and (L)FeIII -O-FeIII (L) complexes (L=1,1-di(pyridin-2-yl)-N,N
      bis(pyridin-2-ylmethyl)ethan-1-amine) underwent reduction under irradiation to
      the FeII state with concomitant oxidation of methanol to methanal, without the
      need for a secondary photosensitizer. Spectroscopic and DFT studies support a
      mechanism in which irradiation results in charge-transfer excitation of a FeIII 
      MU-O-FeIII complex to generate [(L)FeIV =O]2+ (observed transiently during
      irradiation in acetonitrile), and an equivalent of (L)FeII . Under aerobic
      conditions, irradiation accelerates reoxidation from the FeII to the FeIII state
      with O2 , thus closing the cycle of methanol oxidation to methanal.

PMID- 29334588
TI  - Molecular Wire Effects in Phenyleneethynylene Oligomers: Surprising Insights.
AB  - The synthesis and quenching behavior of a series of water-soluble, carboxylate
      carrying phenyleneethynylene oligomers-monomer to tetramer-and their polymers are
      reported; their quenching behavior with different test analytes (paraquat, lead
      salts, mercury salts, picric acid, methylpyridinium iodide) in water were
      investigated, and the results were compared to that of the conjugated polymer.
      Significant but analyte-dependent enhancement effects were found. For monovalent
      quenchers, only the molecular wire effect applies, but for divalent quenchers
      multivalency effects are also important.

PMID- 29334589
TI  - Preparation and evaluation of a deoxycholic-calix[4]arene hybrid-type receptor as
      a chiral stationary phase for HPLC.
AB  - We report the synthesis and enantioseparation characteristics of two novel
      covalently immobilized deoxycholic acid derivatives as chiral stationary phases
      for high-performance liquid chromatography. In the structure of the first
      stationary phase, the 3-position of deoxycholic acid is substituted with a 3,5
      dinitrophenylcarbamoyl group and the second one has an additional calix[4]arene
      attached to the carboxylic group of the deoxycholic acid. The chromatographic
      performance of the stationary phases was evaluated with enantioseparation of N
      (3,5-dinitrobenzoyl)-dl-leucine, N-(3,5-dinitrobenzoyl)-dl-valine, omeprazole,
      diclofop-methyl, dl-mandelic acid and (RS)-pregabalin. Comparison of the
      performance characteristics of the prepared chiral stationary phases provided
      evidence for the active involvement of the calix[4]arene unit in the chiral
      recognition process. Both stationary phases are chemically bonded to the silica
      and can be used in both normal-phase and reversed-phase modes.

PMID- 29334590
TI  - Highly Dispersible and Bioavailable Curcumin but not Native Curcumin Induces
      Brown-Like Adipocyte Formation in Mice.
AB  - SCOPE: The induction of brown-like adipocytes in white adipose tissue (WAT) is a
      potential therapeutic target for the treatment of obesity and metabolic disorders
      via the ability of these cells to release excess energy as heat in association
      with uncoupling protein 1. Some experimental trials suggest that curcumin (a
      yellow pigment from turmeric) has a suppressive effect on the accumulation of
      body fat. However, there is little evidence to show that curcumin induces the
      formation of brown-like adipocytes and the molecular mechanisms involved remain
      elusive. In addition, in most experimental trials, high doses of curcumin are
      administered. METHODS AND RESULTS: Highly dispersible and bioavailable curcumin
      (HC, i.e., 4.5 mg native curcumin kg-1 ) but not the same dose of native curcumin
      induces the formation of brown-like adipocytes in mouse inguinal WAT. Moreover,
      the formation of brown-like adipocytes induced by HC in inguinal WAT may be
      mediated by the production of local norepinephrine from accumulated alternatively
      activated macrophages. CONCLUSION: These novel findings suggest that curcumin
      increases energy expenditure by inducing the formation of brown-like adipocytes
      via a unique molecular mechanism. Importantly, they show that HC has significant
      bioactive effects in vivo at lower doses of curcumin.

PMID- 29334591
TI  - GTEx project maps wide range of normal human genetic variation: A unique catalog
      and follow-up effort associate variation with gene expression across dozens of
      body tissues.

PMID- 29334593
TI  - Reanalysis of clinical whole-exome sequence data yields multiple new diagnoses: A
      time-intensive but successful strategy highlights the benefits of data sharing
      and international collaborations.

PMID- 29334594
TI  - Thoracic aortic aneurysm in patients with loss of function Filamin A mutations:
      Clinical characterization, genetics, and recommendations.
AB  - The frequency and gender distribution of thoracic aortic aneurysm as a
      cardiovascular manifestation of loss-of-function (LOF) X-linked FilaminA (FLNA)
      mutations are not known. Furthermore, there is very limited cardiovascular
      morbidity or mortality data in children and adults. We analyzed cardiac data on
      the largest series of 114 patients with LOF FLNA mutations, both children and
      adults, with periventricular nodular heterotopia (PVNH), including 48 study
      patients and 66 literature patients, median age of 22.0 years (88 F, 26 M, range:
      0-71 years), with 75 FLNA mutations observed in 80 families. Most (64.9%)
      subjects had a cardiac anomaly or vascular abnormality (80.8% of males and 60.2%
      of females). Thoracic aortic aneurysms or dilatation (TAA) were found in 18.4% (n
      = 21), and were associated with other structural cardiac malformations in 57.1%
      of patients, most commonly patent ductus arteriosus (PDA) and valvular
      abnormalities. TAA most frequently involved the aortic root and ascending aorta,
      and sinus of Valsalva aneurysms were present in one third of TAA patients. Six
      TAA patients (28.5%) required surgery (median age 37 yrs, range 13-41 yrs). TAA
      with its associated complications was also the only recorded cause of premature,
      non-accidental mortality in adults (2 M, 2 F). Two adult patients (1 F, 1 M,
      median 38.5 yrs), died of spontaneous aortic rupture at aortic dimensions smaller
      than current recommendations for surgery for other aortopathies. Data from this
      largest series of LOF FLNA mutation patients underscore the importance of serial
      follow-up to identify and manage these potentially devastating cardiovascular
      complications.

PMID- 29334596
TI  - The diversifying field of plant epigenetics.

PMID- 29334597
TI  - Monitoring global tree mortality patterns and trends. Report from the VW
      symposium 'Crossing scales and disciplines to identify global trends of tree
      mortality as indicators of forest health'.

PMID- 29334599
TI  - Sofia J. van Moorsel.

PMID- 29334598
TI  - Time to re-think fungal ecology? Fungal ecological niches are often prejudged.

PMID- 29334600
TI  - Probing promise versus performance in longer read fungal metabarcoding.

PMID- 29334601
TI  - Out of sight, but no longer out of mind - towards an increased recognition of the
      role of soil microbes in plant speciation.

PMID- 29334602
TI  - High-Dose Metformin Plus Temozolomide Shows Increased Anti-tumor Effects in
      Glioblastoma In Vitro and In Vivo Compared with Monotherapy.
AB  - PURPOSE: The purpose of the study is to investigate the efficacy of combined
      treatment with temozolomide (TMZ) and metformin for glioblastoma (GBM) in vitro
      and in vivo. Materials and Methods: We investigated the efficacy of combined
      treatment with TMZ and metformin using cell viability and apoptosis assays. A GBM
      orthotopic mice model was established by inoculation of 5*105 U87 cells and
      treatedwith metformin, TMZ, and the combination for 4weeks. Western blotting and
      immunofluorescence of tumor specimens were analyzed to investigate AMP-activated
      protein kinase (AMPK) and AKT pathway. RESULTS: The combination of TMZ and
      metformin showed higher cytotoxicity than single agents in U87, U251, and A172
      cell lines. A combination of high-dose metformin and TMZ showed the highest
      apoptotic activity. The combination of TMZ and metformin enhanced AMPK
      phosphorylation and inhibited mammalian target of rapamycin phosphorylation, AKT
      phosphorylation, and p53 expression. The median survival of each group was 43.6,
      55.2, 53.2, 65.2, and 71.3 days for control, metformin treatment (2 mg/25 g/day
      or 10 mg/25 g/day), TMZ treatment (15 mg/kg/day), combination treatment with low
      dose metformin and TMZ, and combination treatment with high-dose metformin and
      TMZ, respectively. Expression of fatty acid synthase (FASN) was significantly
      decreased in tumor specimens treated with metformin and TMZ. CONCLUSION: The
      combination of metformin and TMZ was superior to monotherapy using metformin or
      TMZ in terms of cell viability in vitro and survival in vivo. The combination of
      high-dose metformin and TMZ inhibited FASN expression in an orthotopic model.
      Inhibition of FASN might be a potential therapeutic target of GBM.

PMID- 29334603
TI  - Multicenter Phase II Study of Oxaliplatin, Irinotecan, and S-1 as First-line
      Treatment for Patients with Recurrent or Metastatic Biliary Tract Cancer.
AB  - PURPOSE: Although gemcitabine plus cisplatin has been established as the standard
      first-line chemotherapy for patients with advanced biliary tract cancer (BTC),
      overall prognosis remains poor. We investigated the efficacy of a novel triplet
      combination of oxaliplatin, irinotecan, and S-1 (OIS) for advanced BTC. Materials
      and Methods: Chemotherapy-naive patientswith histologically documented
      unresectable or metastatic BTC were eligible for this multicenter, single-arm
      phase II study. Patients received 65 mg/m2 oxaliplatin (day 1), 135 mg/m2
      irinotecan (day 1), and 40 mg/m2 S-1 (twice a day, days 1-7) every 2 weeks.
      Primary endpoint was objective response rate. Targeted exome sequencing for
      biomarker analysis was performed using archival tissue. RESULTS: In total, 32
      patients were enrolled between October 2015 and June 2016. Median age was 64
      years (range, 40 to 76 years), with 24 (75%) male patients; 97% patients had
      metastatic or recurrent disease. Response rate was 50%, and median progression
      free survival and overall survival (OS) were 6.8 months (95% confidence interval
      [CI], 4.8 to 8.8) and 12.5 months (95% CI, 7.0 to 18.0), respectively. The most
      common grade 3-4 adverse events were neutropenia (32%), diarrhea (6%), and
      peripheral neuropathy (6%). TP53 and KRAS mutations were the most frequent
      genomic alterations (42% and 32%, respectively), and KRAS mutations showed a
      marginal relationship with worse OS (p=0.07). CONCLUSION: OIS combination
      chemotherapy was feasible and associated with favorable efficacy outcomes as a
      first-line treatment in patients with advanced BTC. Randomized studies are needed
      to compare OIS with gemcitabine plus cisplatin.

PMID- 29334604
TI  - Breast Conservation Therapy Versus Mastectomy in Patients with T1-2N1 Triple
      Negative Breast Cancer: Pooled Analysis of KROG 14-18 and 14-23.
AB  - PURPOSE: The aim of this study is to compare the treatment outcomes of breast
      conserving surgery (BCS) plus radiotherapy (RT) versus mastectomy for patients
      with pT1-2N1 triple-negative breast cancer (TNBC). Materials and Methods: Using
      two multicenter retrospective studies on breast cancer, a pooled analysis was
      performed among 320 patients with pT1-2N1 TNBC. All patients who underwent BCS
      (n=212) receivedwhole breast RTwith orwithoutregional nodal RT,while nonewho
      underwent mastectomy (n=108)received it. All patients received taxane-based
      adjuvant chemotherapy. The median follow-up periods were 65 months in the BCS+RT
      group, and 74 months in the mastectomy group. RESULTS: The median age of all
      patients was 48 years (range, 24 to 70 years). Mastectomy group had more patients
      with multiple tumors (p < 0.001), no lymphovascular invasion (p=0.001), higher
      number of involved lymph node (p=0.028), and higher nodal ratio >= 0.2 (p=0.037).
      Other characteristics were not significantly different between the two groups.
      The 5-year locoregionalrecurrence-free, disease-free, and overall survivalrates
      of BCS+RT group versus mastectomy group were 94.6% versus 87.7%, 89.5% versus
      80.4%, and 95.0% versus 87.8%, respectively, and the differences were
      statistically significant after adjusting for covariates (p=0.010, p=0.006, and
      p=0.005, respectively). CONCLUSION: In pT1-2N1 TNBC, breast conservation therapy
      achieved better locoregional recurrencefree, disease-free, and overall survival
      rates compared with mastectomy.

PMID- 29334605
TI  - Induction Chemotherapy Plus Concurrent Chemoradiotherapy Versus Concurrent
      Chemoradiotherapy Alone in Locoregionally Advanced Nasopharyngeal Carcinoma in
      Children and Adolescents: A Matched Cohort Analysis.
AB  - PURPOSE: The purpose of this study was to evaluate the long-term clinical outcome
      and toxicity of induction chemotherapy (IC) followed by concomitant
      chemoradiotherapy (CCRT) compared with CCRT alone for the treatment of children
      and adolescent locoregionally advanced nasopharyngeal carcinoma (LACANPC).
      Materials and Methods: A total of 194 locoregionally advanced nasopharyngeal
      carcinoma patients youngerthan 21 years who received CCRT with or without IC
      before were included in the study population. Overall survival (OS) rate,
      progression-free survival (PFS) rate, locoregional recurrence-free survival
      (LRFS) rate, and distant metastasis-free survival (DMFS) rate were assessed by
      the Kaplan-Meier method and a log-rank test. Treatment toxicities were clarified
      and compared between two groups. RESULTS: One hundred and thiry of 194 patients
      received IC+CCRT. Patients who were younger and with more advanced TNM stage were
      more likely to receive IC+CCRT and intensive modulated radiotherapy. The addition
      of IC before CCRT failed to improve survival significantly. The matched analysis
      identified 43 well-balanced patients in both two groups. With a median follow-up
      of 51.5 months, no differences were found between the IC+CCRT group and the CCRT
      group in 5-year OS (83.7% vs. 74.6%, p=0.153), PFS (79.2% vs. 73.4%, p=0.355),
      LRFS (97.7% vs. 88.2%, p=0.083), and DMFS (81.6% vs. 81.6%, p=0.860). N3 was an
      independent prognostic factor predicting poorer OS, PFS, and DMFS. The addition
      of IC was associated with increased rates of grade 3 to 4 neutropenia.
      CONCLUSION: This study failed to demonstrate that adding IC before CCRT could
      provide a significant additional survival benefit for LACANPC patients. Further
      investigations are warranted.

PMID- 29334606
TI  - The Association of Acquired T790M Mutation with Clinical Characteristics after
      Resistance to First-Line Epidermal Growth Factor Receptor Tyrosine Kinase
      Inhibitor in Lung Adenocarcinoma.
AB  - PURPOSE: The main objective of this study was to investigate the relationship
      among the clinical characteristics and the frequency of T790M mutation in
      advanced epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma
      patients with acquired resistance after firstline EGFR-tyrosine kinase inhibitor
      (TKI) treatment. Materials and Methods: We enrolled EGFR-mutant stage IIIB-IV
      lung adenocarcinoma patients, who had progressed to prior EGFR-TKI therapy, and
      evaluated their rebiopsy EGFR mutation status. RESULTS: A total of 205 patients
      were enrolled for analysis. The overall T790M mutation rate of rebiopsy was
      46.3%. The T790M mutation rates among patients with exon 19 deletion mutation,
      exon 21 L858R point mutation, and other mutations were 55.0%, 37.3%, and 27.3%,
      respectively. Baseline exon 19 deletion was associated with a significantly
      higher frequency of T790M mutation (adjusted odds ratio, 2.14; 95% confidence
      interval [CI], 1.20 to 3.83; p=0.010). In the exon 19 deletion subgroup, there
      was a greater prevalence of T790M mutation than other exon 19 deletion subtypes
      in patients with the Del E746-A750 mutation (61.6% vs. 40.6%; odds ratio, 2.35;
      95% CI, 1.01 to 5.49; p=0.049). The progression-free survival (PFS) of first-line
      TKI treatment > 11 months was also associated with a higher T790M mutation rate
      (54.1% vs. 39.3%; adjusted odds ratio, 1.82; 95% CI, 1.02 to 3.25; p=0.044).
      Patients who underwent rebiopsy at metastatic sites had more chance to harbor
      T790M mutation (52.6% vs. 33.8%; adjusted odds ratio, 1.97; 95% CI, 1.06 to 3.67;
      p=0.032). CONCLUSION: PFS of first-line EGFR-TKI, rebiopsy site, EGFR exon 19
      deletion and its subtype Del E746- A750 mutation are associated with the
      frequency of T790M mutation.

PMID- 29334607
TI  - Geographical Variations and Trends in Major Cancer Incidences throughout Korea
      during 1999-2013.
AB  - PURPOSE: We aimed to describe the temporal trends and district-level geographical
      variations in cancer incidences throughout Korea during 1999-2013. Materials and
      Methods: Data were obtained from the Korean National Cancer Incidence Database.
      We calculated the age-standardized cumulative cancerincidences according to sex
      and geographicalregion (metropolitan cities, provinces, and districts) for three
      5-year periods (1999-2003, 2004- 2008, and 2009-2013). Each quintile interval
      contained the same number of regions. Disease maps were created to visualize
      regional differences in the cancer incidences. RESULTS: Substantial differences
      in cancer incidences were observed according to district and cancer type. The
      largest variations between geographical regions were found for thyroid cancer
      among both men and women. There was little variation in the incidences of
      stomach, colorectal, and lung cancer according to geographical region.
      Substantially elevated incidences of specific cancers were observed in Jeollanam
      do (thyroid); Daejeon (colorectum); Jeollanam-do, Gyeongsangbuk-do, and
      Chungcheongbuk-do (lung); Seocho-gu, Gangnam-gu and Seongnam, Bundang-gu (breast
      and prostate); Chungcheong and Gyeongsang provinces (stomach); Ulleung-gun and
      the southern districts of Gyeongsangnam-do and Jeollanam-do (liver); and along
      the Nakdonggang River (gallbladder and biliary tract). CONCLUSION: Mapping
      regional cancer incidences in Korea allowed us to compare the results according
      to geographical region. Our results may facilitate the development of
      infrastructure for systematic cancerincidence monitoring,which could promote the
      planning and implementation of region-specific cancer management programs.

PMID- 29334608
TI  - Factors Associated with Prolonged Patient-Attributable Delay in the Diagnosis of
      Colorectal Cancer.
AB  - PURPOSE: The delayed diagnosis of colorectal cancer (CRC) may be attributable to
      sociodemographic characteristics, to aspects of tumour histopathology or to the
      functioning of the health system. We seek to determine which of these factors
      most influences prolonged patient-attributable delay (PPAD) in the diagnosis and
      treatment of CRC. Materials and Methods: A prospective, multicentre observational
      study was conducted in 22 Spanish hospitals. In total, 1,785 patients were
      recruited to the study between 2010 and 2012 and underwent elective or urgent
      surgery. PPAD is considered to occur when the time elapsed between a patient
      presenting the symptom and him/her seeking attention from the primary care
      physician or hospital emergency department exceeds 180 days. A bivariate analysis
      was performed to assess differences in variables segmented by tumour location and
      patient delay. Multivariate logistic regression analysis was performed on the
      outcome variable, PPAD. RESULTS: The rate of PPAD among this population was
      12.1%. PPAD was significantly associated with altered bowel rhythm (odds ratio
      [OR], 1.36; 95% confidence interval [CI], 1.02 to 1.83) and with adenocarcinoma
      histology, in comparison with mucinous adenocarcinoma (OR, 2.03; 95% CI, 1.11 to
      3.71). Other sociocultural factors and clinicopathological features were not
      independent predictors of PPAD. CONCLUSION: Many patients do not consider altered
      bowel rhythm an alarming symptom, warranting a visit to the doctor. PPAD could be
      reduced by improving health education, raising awareness of CRC-related symptoms.

PMID- 29334609
TI  - Score for the Survival Probability in Metastasis Breast Cancer: A Nomogram-Based
      Risk Assessment Model.
AB  - PURPOSE: Survival of metastatic breast cancer (MBC) patient remains unknown and
      varies greatly from person to person. Thus, we aimed to construct a nomogram to
      quantify the survival probability of patients with MBC. Materials and Methods: We
      had included 793 MBC patients and calculated trends of case fatality rate by
      Kaplan-Meier method and joinpoint regression. Six hundred thirty-four patients
      with MBC between January 2004 and July 2011 and 159 patients with MBC between
      August 2011 and July 2013 were assigned to training cohort and internal
      validation cohort, respectively. We constructed the nomogram based on the results
      of univariable and multivariable Cox regression analyses in the training cohort
      and validated the nomogram in the validation cohort. Concordance index and
      calibration curves were used to assess the effectiveness of nomogram. RESULTS:
      Case fatality rate of MBC was increasing (annual percentage change [APC], 21.6;
      95% confidence interval [CI], 1.0 to 46.3; p < 0.05) in the first 18 months and
      then decreased (APC, -4.5; 95% CI, -8.2 to -0.7; p < 0.05). Metastasis-free
      interval, age, metastasis location, and hormone receptor status were independent
      prognostic factors and were included in the nomogram, which had a concordance
      index of 0.69 in the training cohort and 0.67 in the validation cohort.
      Calibration curves indicated good consistency between the two cohorts at 1 and 3
      years. CONCLUSION: In conclusion, the fatality risk of MBC was increasing and
      reached the summit between 13th and 18th month afterthe detection of MBC. We have
      developed and validated a nomogram to predict the 1- and 3-year survival
      probability in MBC.

PMID- 29334610
TI  - Phase II Study of Dovitinib in Patients with Castration-Resistant Prostate Cancer
      (KCSG-GU11-05).
AB  - PURPOSE: Fibroblast growth factor (FGF) signals are important in carcinogenesis
      and progression of prostate cancer. Dovitinib is an oral, pan-class inhibitor of
      vascular endothelial growth factor receptor (VEGFR), platelet-derived growth
      factor receptor, and fibroblast growth factor receptor (FGFR). We evaluated the
      efficacy and toxicity of dovitinib in men with metastatic castration resistant
      prostate cancer (mCRPC). Materials and Methods: This study was a single-arm,
      phase II, open-label, multicenter trial of dovitinib 500 mg/day (5-days-on/2-days
      off schedule). The primary endpointwas 16-week progression-free survival (PFS).
      Secondary endpoints were overall survival (OS), toxicity and prostate-specific
      antigen (PSA) response rate. Biomarker analyses for VEGFR2, FGF23, and FGFR2
      using multiplex enzyme-linked immunosorbent assay was performed. RESULTS: Forty
      four men were accrued from 11 hospitals. Eighty percent were post-docetaxel.
      Median PSA was 100 ng/dL, median age was 69, 82% had bone metastases, and 23% had
      liver metastases. Median cycles of dovitinibwas 2 (range, 0 to 33). Median PFSwas
      3.67 months (95% confidence interval [CI], 1.36 to 5.98) and median OS was 13.70
      months (95% CI, 0 to 27.41). Chemotherapy-naive patients had longer PFS (17.90
      months; 95% CI, 9.23 to 28.57) compared with docetaxel-treated patients (2.07
      months; 95% CI, 1.73 to 2.41; p=0.001) and the patients with high serum VEGFR2
      level over median level (7,800 pg/mL) showed longer PFS compared with others
      (6.03 months [95% CI, 4.26 to 7.80] vs. 1.97 months [95% CI, 1.79 to 2.15],
      p=0.023). Grade 3 related adverse events were seen in 40.9% of patients. Grade 1
      2 nausea, diarrhea, fatigue, anorexia, and all grade thrombocytopenia are common.
      CONCLUSION: Dovitinib showed modest antitumor activity with manageable toxicities
      in men with mCRPC. Especially, patients who were chemo-naive benefitted from
      dovitinib.

PMID- 29334611
TI  - Understanding Complex Tribofilms by Means of H3BO3-B2O3 Model Glasses.
AB  - The discovery of the spontaneous reaction of boric oxides with moisture in the
      air to form lubricious H3BO3 films has led to great interest in the tribology of
      boron compounds in general. Despite this, a study of the growth kinetics of H3BO3
      on a B2O3 substrate under controlled relative humidity (RH) has not yet been
      reported in the literature. Here, we describe the tribological properties of
      H3BO3-B2O3 glass systems after aging under controlled RH over different lengths
      of time. A series of tribological tests has been performed applying a normal load
      of 15 N, at both room temperature and 100  degrees C in YUBASE 4 oil. In
      addition, the cause of H3BO3 film failure under high-pressure and high
      temperature conditions has been studied to find out whether the temperature, the
      tribostress, or both influence the removal of the lubricious film from the
      contact points. The following techniques were exploited: confocal Raman
      spectroscopy to characterize the structure and chemical nature of the glass
      systems, environmental scanning electron microscopy to examine the morphology of
      the H3BO3 films developed, atomic force microscopy to monitor changes in
      roughness as a consequence of the air exposure, focused-ion-beam scanning
      electron microscopy to measure the average thickness of the H3BO3 films grown
      over various times on B2O3 glass substrates and to reveal the morphology of the
      sample in the vertical section, tribological tests to shed light on the system's
      lubricating properties, and finally small-area X-ray photoelectron spectroscopy
      to investigate the composition of the transfer film formed on the steel ball
      while tribotesting.

PMID- 29334612
TI  - TEMPO-Oxidized Bacterial Cellulose Pellicle with Silver Nanoparticles for Wound
      Dressing.
AB  - Biocompatible bacterial cellulose pellicle (BCP) is a candidate for biomedical
      material such as wound dressing. However, due to lack of antibacterial activity,
      to grant BCP with the property is crucial for its biomedical application. In the
      present study, BCP was modified by 2,2,6,6-tetramethylpiperidine-1-oxyl radical
      (TEMPO)-mediated oxidation using TEMPO/NaClO/NaBr system at pH 10 to form TEMPO
      oxidized BCP (TOBCP) with anionic C6 carboxylate groups. The TOBCP was
      subsequently ion-exchanged in AgNO3 solution and silver nanoparticles (AgNP) with
      diameter of ~16.5 nm were in situ synthesized on TOBC nanofiber surfaces by
      thermal reduction without using a reducing agent. Field emission scanning
      electron microscopy, X-ray diffraction, X-ray photoelectron spectra, Fourier
      transform infrared spectroscopy, and thermogravimetric analysis were carried out
      to confirm morphology and structure of the pellicles with AgNP. The AgNP
      continuously released Ag+ with a rate of 12.2%/day at 37  degrees C in 3 days.
      The TOBCP/AgNP exhibited high biocompatibility according to the result of in
      vitro cytotoxicity test (cell viability >95% after 48 h of incubation) and showed
      significant antibacterial activities of 100% and 99.2% against E. coli and S.
      aureus, respectively. Hence, the highly biocompatible and highly antibacterial
      TOBCP/AgNP prepared in the present study is a promising candidate for wound
      dressing.

PMID- 29334613
TI  - Reduced miR-144-3p expression in serum and bone mediates osteoporosis
      pathogenesis by targeting RANK.
AB  - Osteoblasts and osteoclasts are responsible for the formation and resorption of
      bone, respectively. An imbalance between these two processes results in a disease
      called osteoporosis, in which a decreased level of bone strength increases the
      risk of a bone fracture. MicroRNAs (miRNAs) are small non-coding RNA molecules of
      18-25 nucleotides that have been previously shown to control bone metabolism by
      regulating osteoblast and osteoclast differentiation. In this study, we detected
      the expression pattern of 10 miRNAs in serum samples from patients with
      osteoporosis, and identified the altered expression of 6 miRNAs by comparison
      with patients without osteoporosis. We selected miR-144-3p for further
      investigation, and showed that it regulates osteoclastogenesis by targeting RANK,
      and that it is conserved amongst vertebrates. Disrupted expression of miR-144-3p
      in CD14+ peripheral blood mononuclear cells changed TRAP activity and the
      osteoclast-specific genes TRAP, cathepsin K (CTSK), and NFATC. TRAP staining, CCK
      8, and flow cytometry analyses revealed that miR-144-3p also affects osteoclast
      formation, proliferation, and apoptosis. Together, these results indicate that
      miR-144-3p critically mediates bone homeostasis, and thus, represents a promising
      novel therapeutic candidate for the treatment of this disease.

PMID- 29334614
TI  - Perceptions of exercise screening among older adults.
AB  - Prephysical activity screening is important for older adults' participating in
      physical activity. Unfortunately, many older adults face barriers to exercise
      participation and thus, may not complete proper physical activity screening. The
      purpose of this project was to conduct a thematic analysis of perceptions and
      experiences of community-dwelling older adults regarding prephysical activity
      screening (i.e., Get Active Questionnaire (GAQ) and a standardized exercise
      stress test). A convenience sample of adults (male n = 58, female n = 54) aged 75
      +/- 7 years living in the City of London, Ontario, Canada, was used. Participants
      completed a treadmill stress test and the GAQ at a research laboratory for
      community-based referrals. One week later, participants completed the GAQ again
      and were asked questions by a research assistant about their perceptions of the
      screening process. Thematic analysis of the responses was conducted. The results
      indicated that older adults view physical activity screening as acceptable, but
      not always necessary. Also, the experiences expressed by this sample of older
      adults indicated that physical activity screening can contribute to continued
      confidence (through reassurance) and can contribute to increased motivation
      (through yearly fitness results) in exercise participation. In conclusion, older
      adults may perceive screening as supportive in exercise adoption, if screening is
      simple, convenient, and supports older adults' motivation and confidence to
      exercise.

PMID- 29334615
TI  - Hemodynamic and metabolic responses to self-paced and ramp-graded exercise
      testing protocols.
AB  - Recent examinations have shown lower maximal oxygen consumption during
      traditional ramp (RAMP) compared with self-paced (SPV) graded exercise testing
      (GXT) attributed to differences in cardiac output. The current study examined the
      differences in hemodynamic and metabolic responses between RAMP and SPV during
      treadmill exercise. Sixteen recreationally trained men (aged23.7 +/- 3.0 years)
      completed 2 separate treadmill GXT protocols. SPV consisted of five 2-min stages
      (10 min total) of increasing speed clamped by the Borg RPE6-20 scale. RAMP
      increased speed by 0.16 km/h every 15 s until volitional exhaustion. All testing
      was performed at 3% incline. Oxygen consumption was measured via indirect
      calorimetry; hemodynamic function was measured via thoracic impedance and blood
      lactate (BLa-) was measured via portable lactate analyzer. Differences between
      SPV and RAMP protocols were analyzed as group means by using paired-samples t
      tests (R Core Team 2017). Maximal values for SPV and RAMP were similar (p > 0.05)
      for oxygen uptake (47.1 +/- 3.4 vs. 47.4 +/- 3.4 mL.kg-1.min-1), heart rate (198
      +/- 5 vs. 200 +/- 6 beats.min-1), ventilation (158.8 +/- 20.7 vs. 159.3 +/- 19.0
      L.min-1), cardiac output (26.9 +/- 5.5 vs. 27.9 +/- 4.2 L.min-1), stroke volume
      (SV) (145.9 +/- 29.2 vs. 149.8 +/- 25.3 mL.beat-1), arteriovenous oxygen
      difference (18.5 +/- 3.1 vs. 19.7 +/- 3.1 mL.dL-1), ventilatory threshold (VT)
      (78.2 +/- 7.2 vs. 79.0% +/- 7.6%), and peak BLa- (11.7 +/- 2.3 vs. 11.5 +/- 2.4
      mmol.L-1), respectively. In conclusion, SPV elicits similar maximal hemodynamic
      responses in comparison to RAMP; however, SV kinetics exhibited unique
      characteristics based on protocol. These results support SPV as a feasible GXT
      protocol to identify useful fitness parameters (maximal oxygen uptake, oxygen
      uptake kinetics, and VT).

PMID- 29334616
TI  - Preoperative Breast Magnetic Resonance Imaging Use by Breast Density and Family
      History of Breast Cancer.
AB  - BACKGROUND: Use of preoperative breast magnetic resonance imaging (MRI) among
      women with a new breast cancer has increased over the past decade. MRI use is
      more frequent in younger women and those with lobular carcinoma, but associations
      with breast density and family history of breast cancer are unknown. MATERIALS
      AND METHODS: Data for 3075 women ages >65 years with stage 0-III breast cancer
      who underwent breast conserving surgery or mastectomy from 2005 to 2010 in the
      Breast Cancer Surveillance Consortium were linked to administrative claims data
      to assess associations of preoperative MRI use with mammographic breast density
      and first-degree family history of breast cancer. Multivariable logistic
      regression estimated adjusted odds ratios (OR) and 95% confidence intervals (95%
      CI) for the association of MRI use with breast density and family history,
      adjusting for woman and tumor characteristics. RESULTS: Overall, preoperative MRI
      use was 16.4%. The proportion of women receiving breast MRI was similar by breast
      density (17.6% dense, 16.9% nondense) and family history (17.1% with family
      history, 16.5% without family history). After adjusting for potential
      confounders, we found no difference in preoperative MRI use by breast density (OR
      = 0.95 for dense vs. nondense, 95% CI: 0.73-1.22) or family history (OR = 0.99
      for family history vs. none, 95% CI: 0.73-1.32). CONCLUSIONS: Among women aged
      >65 years with breast cancer, having dense breasts or a first-degree relative
      with breast cancer was not associated with greater preoperative MRI use. This
      utilization is in keeping with lack of evidence that MRI has higher yield of
      malignancy in these subgroups.

PMID- 29334617
TI  - Chains of risk for alcohol use disorder: Mediators of exposure to neighborhood
      deprivation in early and middle childhood.
AB  - Our goal was to test a cascade model to identify developmental pathways, or
      chains of risk, from neighborhood deprivation in childhood to alcohol use
      disorder (AUD) in young adulthood. Using Swedish general population data, we
      examined whether exposure to neighborhood deprivation during early and middle
      childhood was associated with indicators of social functioning in adolescence and
      emerging adulthood, and whether these were predictive of AUD. Structural equation
      models showed exposure to neighborhood deprivation was associated with lower
      school achievement during adolescence, poor social functioning during emerging
      adulthood, and the development of AUD for both males and females. Understanding
      longitudinal pathways from early exposure to adverse environments to later AUD
      can inform prevention and intervention efforts.

PMID- 29334619
TI  - Comparisons between a new point kernel-based scheme and the infinite plane source
      assumption method for radiation calculation of deposited airborne radionuclides
      from nuclear power plants.
AB  - Radiation from the deposited radionuclides is indispensable information for
      environmental impact assessment of nuclear power plants and emergency management
      during nuclear accidents. Ground shine estimation is related to multiple physical
      processes, including atmospheric dispersion, deposition, soil and air radiation
      shielding. It still remains unclear that whether the normally adopted "infinite
      plane" source assumption for the ground shine calculation is accurate enough,
      especially for the area with highly heterogeneous deposition distribution near
      the release point. In this study, a new ground shine calculation scheme, which
      accounts for both the spatial deposition distribution and the properties of air
      and soil layers, is developed based on point kernel method. Two sets of "detector
      centered" grids are proposed and optimized for both the deposition and radiation
      calculations to better simulate the results measured by the detectors, which will
      be beneficial for the applications such as source term estimation. The evaluation
      against the available data of Monte Carlo methods in the literature indicates
      that the errors of the new scheme are within 5% for the key radionuclides in
      nuclear accidents. The comparisons between the new scheme and "infinite plane"
      assumption indicate that the assumption is tenable (relative errors within 20%)
      for the area located 1 km away from the release source. Within 1 km range, the
      assumption mainly causes errors for wet deposition and the errors are independent
      of rain intensities. The results suggest that the new scheme should be adopted if
      the detectors are within 1 km from the source under the stable atmosphere
      (classes E and F), or the detectors are within 500 m under slightly unstable
      (class C) or neutral (class D) atmosphere. Otherwise, the infinite plane
      assumption is reasonable since the relative errors induced by this assumption are
      within 20%. The results here are only based on theoretical investigations. They
      should be further thoroughly evaluated with real measurements in the future.

PMID- 29334618
TI  - Exploring masculinities, sexual health and wellbeing across areas of high
      deprivation in Scotland: The depth of the challenge to improve understandings and
      practices.
AB  - Within and across areas of high deprivation, we explored constructions of
      masculinity in relation to sexual health and wellbeing, in what we believe to be
      the first UK study to take this approach. Our sample of 116 heterosexual men and
      women age 18-40 years took part in individual semi-structured interviews (n = 35)
      and focus group discussions (n = 18), across areas in Scotland. Drawing on a
      socio-ecological framework, findings revealed experience in places matter, with
      gender practices rooted in a domestically violent milieu, where localised, socio
      cultural influences offered limited opportunities for more egalitarian
      performances of masculinity. We discuss the depths of the challenge in
      transforming masculinities in relation to sexual health and wellbeing in such
      communities.

PMID- 29334620
TI  - Evaluation of abundance of artificial radionuclides in food products in South
      Korea and sources.
AB  - Food samples are collected nationwide from January 2016 to February 2017 and
      their contents of artificial radionuclides are measured to address the growing
      concerns regarding the radioactive contamination of food products in Korea.
      Specifically, 900 food samples are collected for this study and their contents of
      representative artificial radionuclides 134Cs, 137Cs, 239,240Pu, and 90Sr are
      analyzed. The analysis shows that the activity concentrations of 137Cs in fish
      range from minimum detectable activity (MDA) to 340 mBq/kg of fresh weight. The
      concentration factor (CF) determined for 137Cs as a measure of its
      bioavailability is calculated to be ca. 74 and found to be very similar to that
      (100) recommended by the International Atomic Energy Agency. With an MDA of
      <0.221 mBq/kg, the results reveal that 239,240Pu values in fish are below the
      MDA. The activity concentrations of 137Cs and 90Sr are lower than the MDA in both
      shellfish and seaweed, while the activity concentrations of 239,240Pu in
      shellfish range from 0.26 to 2.18 mBq/kg, and for seaweed samples range from 2.07
      to 3.38 mBq/kg. The atom ratios of 240Pu/239Pu in shellfish caught at the Korean
      coast vary from 0.209 to 0.237, with a mean of 0.227. The higher 240Pu/239Pu atom
      ratio determined in shellfish is thought to be caused by the plutonium
      transported from the Pacific Proving Grounds rather than other sources such as
      the Fukushima nuclear power plant accident. The activity concentrations of 137Cs
      in mushrooms are found to vary from 1.0 to 21.4 Bq/kg, with the highest
      concentrations observed in the Oak (shiitake) and Sarcodon asparatus. 134Cs is
      detected in three mushroom specimens collected from Jeju Island and about 3-3.6%
      of 137Cs present in the wild mushrooms native to the Jeju Island are introduced
      as a result of the Fukushima nuclear plant accident. The annual effective doses
      of 137Cs received through consumption of mushrooms and fish are 2.0 * 10-4 mSv yr
      1 and 3.9 * 10-5 mSv yr-1, and those values are negligible compared to the annual
      effective doses limit of 1 mSv yr-1.

PMID- 29334621
TI  - Taurine as a green bio-organic catalyst for the preparation of bio-active
      barbituric and thiobarbituric acid derivatives in water media.
AB  - Taurine, a beta-amino acid that is abundantly available in the tissues of human
      and animals, is efficiently used as a green bio-organic catalyst in the
      preparation of some of the biologically active barbituric and thiobarbituric acid
      derivatives. In the presence of taurine, 5-Arylidene (thio) barbituric acid
      derivatives were prepared via Knovenagel reaction between aldehydes and
      (thio)barbituric acid. Using this reagent also pyrano[2,3-d]pyrimidinone(thione)
      derivatives were synthesized through a three-component reaction between
      aldehydes, (thio)barbituric and malononitrile. Both reactions are performed in
      water with good to excellent yields during acceptable reaction times. No organic
      solvent was used during reaction or separation steps and no extra-purification
      was exerted. Meanwhile, reusability of taurine was easy and noticeably high.

PMID- 29334622
TI  - Pyridazinone hybrids: Design, synthesis and evaluation as potential
      anticonvulsant agents.
AB  - A series of new hybrid benzothiazole containing pyridazinones derivatives were
      designed and synthesized fulfilling all the pharmacophoric requirements essential
      for the anticonvulsant activity. In-silico and in vitro studies revealed that
      some of these hybrid derivatives demonstrated admirable GABA AT inhibitory
      activity. An attempt has also been made to validate the results of in vitro GABA
      AT inhibition of the most potent compound SPS-5F (IC50 9.10 MUM) through in vivo
      anticonvulsant screening. Compound SPS-5F administration significantly increases
      the whole brain GABA level, might be through the inhibition of GABA AT enzyme.

PMID- 29334623
TI  - An alternative carrier solvent for fingermark enhancement reagents.
AB  - Solstice(r) Performance Fluid (PF), trans-1-chloro-3,3,3-trifluoropropene, is
      presented as an alternative to HFE7100, methoxy-nonafluorobutane, as a carrier
      solvent in a number of chemical formulations used for the visualisation of latent
      fingermarks. The supply of HFE7100 may be at risk due to a recent European Union
      regulation to control global warming. Laboratory trials using split depletions
      and a pseudo-operational trial of 1000 porous samples have shown that Solstice(r)
      PF is a viable alternative to HFE7100 for the chemical formulations of ninhydrin
      and 1,2-indanedione. Other preliminary trials have also indicated that
      Solstice(r) PF can be used as a carrier solvent for the zinc toning of marks
      found using ninhydrin as well as the alpha-naphtholflavone fixative solution for
      iodine developed marks. Results from the pseudo-operational trial demonstrate
      that the number of marks detected by ninhydrin and 1,2-indanedione formulations
      for each carrier solvent is comparable. When compared to HFE7100, advantages of
      Solstice(r) PF include a very low global warming potential and atmospheric
      lifetime in addition to a higher wetting index and lower costs. This study also
      provides a validation study that supports the potential replacement of DFO with
      1,2-indanedione.

PMID- 29334624
TI  - Adequate vitamin D3 skin synthesis versus erythema risk in the Northern
      Hemisphere midlatitudes.
AB  - Health-optimum-exposure index (HOEI) is proposed to assess if the prescribed
      amount of vitamin D3 (target value) could be synthesized in the human skin
      without erythema appearance. It is defined as the ratio between the vitamin D3
      quantity received during the maximum allowed outdoor exposure without erythema
      risk and the target value. Sunbathing is safe for HOEI>1 and 1/HOEI represents a
      part of minimal erythema dose (MED) necessary to obtain the target value. We
      examine the following targets: a vitamin D3 quantity equivalent to 1000 IU
      vitamin D3 taken orally, and an optimal vitamin D3 quantity defined by Krzyscin
      et al. (2016). The biologically weighted (previtamin D3 and erythemal) doses from
      the Northern Hemisphere midlatitudinal stations are analyzed to find HOEI
      dependence on personal and meteorological factors. HOEI depends mostly on the
      exposed skin area, person's age, and sun elevation at noon but not on the
      Fitzpatrick skin phototype. We found that only young adults (<21 yr) could safely
      obtain vitamin D3 quantity, which is equivalent to 1000 IU taken orally, almost
      throughout the whole year. Duration of such exposures appears <1 h only in the
      warm subperiods of the year (April-September) for a person with minimal erythema
      dose of 330 J m-2. Exposing larger part of the body (~30%) enables the oldest
      persons (>59 yr) to reach 1000 IU target during warm days in spring and summer.
      The optimal daily vitamin D3 quantity could only be synthesized only by young
      adults for about 40-60% of days in the May-August period if they expose at least
      1/3 part of their body surface area. Vitamin D3 supplementation seems to be
      necessary over the whole year for the oldest persons with daily dosage of ~2000
      IU but reduced to ~1000 IU in summer for sunseekers exposing significant part of
      the body.

PMID- 29334625
TI  - Light quality affects flavonoid production and related gene expression in
      Cyclocarya paliurus.
AB  - Understanding the responses of plant growth and secondary metabolites to
      differential light conditions is very important to optimize cultivation
      conditions of medicinal woody plants. As a highly valued and multiple function
      tree species, Cyclocarya paliurus is planted and managed for timber production
      and medical use. In this study, LED-based light including white light (WL), blue
      light (BL), red light (RL), and green light (GL) were used to affect leaf biomass
      production, flavonoid accumulation and related gene expression of one-year C.
      paliurus seedlings in controlled environments. After the treatments of 60 days,
      the highest leaf biomass appeared in the treatment of WL, while the lowest leaf
      biomass was found under GL. Compared to WL, the total flavonoid contents of C.
      paliurus leaves were significantly higher in BL, RL, and GL, but the highest
      values of selected flavonoids (kaempferol, isoquercitrin and quercetin) were
      observed under BL. Furthermore, the greatest yields of total and selected
      flavonoids in C. paliurus leaves per seedling were also achieved under BL,
      indicating that blue light was effective for inducing the production of
      flavonoids in C. paliurus leaves. Pearson's correlation analysis showed that
      there were significantly positive correlations between leaf flavonoid content and
      relative gene expression of key enzymes (phenylalanine ammonia lyase, PAL; 4
      coumaroyl CoA-ligase, 4CL; and chalcone synthase, CHS) in the upstream, which
      converting phenylalanine into the flavonoid skeleton of tetrahydroxy chalcone. It
      is concluded that manipulating light quality may be potential mean to achieve the
      highest yields of flavonoids in C. paliurus cultivation, however this needs to be
      further verified by more field trials.

PMID- 29334626
TI  - Parenting predicts Strange Situation cortisol reactivity among children adopted
      internationally.
AB  - The functioning of the hypothalamic pituitary adrenal (HPA) axis can be altered
      by adverse early experiences. Recent studies indicate that children who were
      adopted internationally after experiencing early institutional rearing and
      unstable caregiving exhibit blunted HPA reactivity to stressful situations. The
      present study examined whether caregiving experiences post-adoption further
      modulate children's HPA responses to stress. Parental sensitivity during
      naturalistic parent-child play interactions was assessed for 66 children (M age =
      17.3 months, SD = 4.6) within a year of being adopted internationally.
      Approximately 8 months later, children's salivary cortisol levels were measured
      immediately before as well as 15 and 30 min after a series of brief separations
      from the mother in an unfamiliar laboratory setting. Latent growth curve modeling
      indicated that experiencing more parental sensitivity predicted increased
      cortisol reactivity to the stressor. Although half the families received an
      intervention designed to improve parental sensitivity, the intervention did not
      significantly alter children's cortisol outcomes. These findings suggest that
      post-adoption parental sensitivity may help normalize the HPA response to stress
      among children adopted internationally.

PMID- 29334627
TI  - Testosterone, DHEA and DHEA-S in patients with schizophrenia: A systematic review
      and meta-analysis.
AB  - Neuroactive steroids, including testosterone, dehydroepiandrosterone (DHEA) and
      its sulfate (DHEA-S) might play an important role in the pathophysiology of
      schizophrenia. Therefore, we performed a systematic review and meta-analysis of
      studies comparing the levels of testosterone, DHEA and DHEA-S in patients with
      schizophrenia and healthy controls. We searched electronic databases from their
      inception until Oct 29, 2017. Effect size (ES) estimates were calculated as
      Hedges' g. Data analysis was performed using random-effects models. Our analysis
      included 34 eligible studies, representing 1742 patients and 1604 controls. Main
      analysis revealed elevated DHEA-S levels in the whole group of patients (ES =
      0.75, 95%CI: 0.23-1.28, p = 0.005). In subgroup analyses, patients with first
      episode psychosis (FEP) had significantly higher levels of free testosterone (ES
      = 1.21, 95%CI: 0.30-2.12, p = 0.009) and DHEA-S (ES = 1.19, 95%CI: 0.66-1.71, p <
      0.001). Acutely relapsed schizophrenia patients presented significantly higher
      levels of total testosterone (ES = 0.50, 95%CI: 0.21-0.70, p < 0.001). Total
      testosterone levels were also elevated in stable multi-episode schizophrenia
      (sMES) females (ES = 0.56, 95%CI: 0.33-0.80, p < 0.001) and reduced in sMES males
      (ES = -0.62, 95%CI: -1.07 to 0.18, p = 0.006). Increased levels of biologically
      active, free testosterone and DHEA-S in FEP suggest that these alterations might
      appear as a response to stress that becomes blunted during subsequent
      exacerbations of schizophrenia. Differential changes in total testosterone levels
      in male and female sMES patients might represent medication effects related to
      prolactin-releasing effects of antipsychotics.

PMID- 29334628
TI  - Production and characterization of human induced pluripotent stem cells (iPSCs)
      from Joubert Syndrome: CSSi001-A (2850).
AB  - Joubert Syndrome (JS) is a rare autosomal recessive or X-linked condition
      characterized by a peculiar cerebellar malformation, known as the molar tooth
      sign (MTS), associated with other neurological phenotypes and multiorgan
      involvement. JS is a ciliopathy, a spectrum of disorders whose causative genes
      encode proteins involved in the primary cilium apparatus. In order to elucidate
      ciliopathy-associated molecular mechanisms, human induced pluripotent stem cells
      (hiPSCs) were derived from a patient affected by JS carrying a homozygous
      missense mutation in the AHI1 gene (p.H896R) that encodes a protein named
      Jouberin.

PMID- 29334629
TI  - Generation of a human induced pluripotent stem cell line (CSC-42) from a patient
      with sporadic form of Parkinson's disease.
AB  - Skin fibroblasts were collected from a 44-year-old patient with sporadic case of
      Parkinson's disease (PD). The non-integrating Sendai virus vector encoding
      OCT3/4, SOX2, c-MYC and KLF4 was used to reprogram fibroblasts into induced
      pluripotent stem cells (iPSCs). Generated iPSCs had normal karyotypes, expressed
      common stem cell markers, and were capable of differentiating into all three germ
      layers. Generated line could be used for PD modeling to understand the mechanisms
      that influence the disorder.

PMID- 29334630
TI  - Generation of an integration-free induced pluripotent stem cell line (CSC-43)
      from a patient with sporadic Parkinson's disease.
AB  - An induced pluripotent stem cell (iPSC) line was generated from a 36-year-old
      patient with sporadic Parkinson's disease (PD). Skin fibroblasts were
      reprogrammed using the non-integrating Sendai virus technology to deliver OCT3/4,
      SOX2, c-MYC and KLF4 factors. The generated cell line (CSC-43) exhibits
      expression of common pluripotency markers, in vitro differentiation into three
      germ layers and normal karyotype. This iPSC line can be used to study the
      mechanisms underlying the development of PD.

PMID- 29334631
TI  - Acceptability of intervention materials to decrease risk for alcohol and
      medication interactions among older adults.
AB  - BACKGROUND: The majority of older adults take prescription or over-the-counter
      medications and about half consume alcohol regularly. Despite high risk for
      alcohol medication interactions (AMI), few community-level interventions exist to
      prevent AMI. The current study assessed the acceptability of educational
      materials created for use in a brief intervention to prevent AMI among older
      adults. METHODS: Older adults from two senior centers reviewed intervention
      materials (poster, patient and pharmacist brochures, and public service
      announcement) and participated in a pre and post-test to provide feedback and to
      assess changes in AMI-related awareness and intentions. RESULTS: Post-test data
      showed positive feedback and an increase in participant understanding of AMI
      prevention, with statistically significant changes in perceived importance of
      messaging surrounding risky alcohol use and potential consequences of AMI.
      DISCUSSION: The intervention materials were positively received, and participant
      feedback indicated that the collective presentation of all the materials was the
      most preferred tool for educating the community. With positive trends in
      awareness and knowledge, intervention effectiveness needs to be further evaluated
      in future large-scale studies. LESSONS LEARNED: This study provides health
      education specialists with tools to prevent alcohol and medication interactions
      among older adults.

PMID- 29334632
TI  - Capillary electrophoresis-mass spectrometry for targeted and untargeted analysis
      of the sub-5 kDa urine metabolome of patients with prostate or bladder cancer: A
      feasibility study.
AB  - Targeted and untargeted analyses of the sub-5 kDa urine metabolome of
      genitourinary cancer patients (prostate and/or bladder) were performed without
      chemical derivatization using capillary electrophoresis-electrospray ionization
      mass spectrometry (CE-ESI-MS). For targeted analysis, endogenous levels of
      sarcosine and 5 other amino acid metabolites implicated in the progression of
      prostate cancer were quantified in four patients and in a pooled urine sample
      from healthy volunteers. An untargeted analysis (m/z 50 to 850) of patient urine
      was performed using the same CE-ESI-MS system identifying over 400 distinct
      molecular features per patient. All patient urine samples were collected at
      prostatectomy/cystectomy via catheter. Patient urine samples were filtered by
      centrifugation, with endogenous sarcosine enriched by solid-phase extraction, and
      the processed samples loaded onto CE-ESI-MS for analysis. Diagnostic information,
      digital pathological slides, and tissue samples were collected and stored in a
      comprehensive biobanking database. The introduction of urine sample collection
      into the surgery workflow was facile and is a promising strategy for addressing
      the translational research challenge of moving smoothly from "chromatogram to
      nomogram".

PMID- 29334633
TI  - Fluorous-assisted metal chelate affinity extraction for nucleotides followed by
      HILIC-MS/MS analysis.
AB  - We herein developed a selective method for the determination of nucleotides by
      fluorous-assisted metal chelate affinity extraction followed by hydrophilic
      interaction liquid chromatography (HILIC) combined with tandem mass spectrometric
      (MS/MS) analysis. In this study, the nucleotides were selectively chelated by
      Fe(III)-immobilized perfluoroalkyliminodiacetic acid, and the resulting chelates
      were subsequently extracted into a fluorous solvent. The nucleotides present in
      the fluorous solvent were then back-extracted into a non-fluorous solution, such
      as a solution of ammonia in aqueous acetonitrile. The resulting non-fluorous
      solution containing the nucleotides was then directly injected into an amide-type
      HILIC column using a mixture of acetonitrile and aqueous ammonium bicarbonate as
      the mobile phase for gradient elution, and the nucleotides were detected using
      the negative electrospray ionization MS/MS mode. In this method, the extraction
      recoveries of the nucleotides ranged from 43.2 to 94.7% within a relative
      standard deviation of 17%. This method enabled the determination of intracellular
      concentrations of nucleotides.

PMID- 29334634
TI  - Equine in vivo-derived metabolites of the SARM LGD-4033 and comparison with human
      and fungal metabolites.
AB  - LGD-4033 has been found in human doping control samples and has the potential for
      illicit use in racehorses as well. It belongs to the pharmacological class of
      selective androgen receptor modulators (SARMs) and can stimulate muscle growth,
      much like anabolic steroids. However, SARMs have shown superior side effect
      profiles compared to anabolic steroids, which arguably makes them attractive for
      use by individuals seeking an unfair advantage over their competitors. The
      purpose of this study was to investigate the metabolites formed from LGD-4033 in
      the horse in order to find suitable analytical targets for doping controls. LGD
      4033 was administered to three horses after which plasma and urine samples were
      collected and analyzed for metabolites using ultra high performance liquid
      chromatography coupled to a high resolution mass spectrometer. In horse urine,
      eight metabolites, both phase I and phase II, were observed most of which had not
      been described in other metabolic systems. Six of these were also detected in
      plasma. The parent compound was detected in plasma, but not in non-hydrolyzed
      urine. The longest detection times were observed for unchanged LGD-4033 in plasma
      and in urine hydrolyzed with beta-glucuronidase and is thus suggested as the
      analytical target for doping control in the horse. The metabolite profile
      determined in the horse samples was also compared to those of human urine and
      fungal incubate from Cunninghamella elegans. The main human metabolite,
      dihydroxylated LGD-4033, was detected in the horse samples and was also produced
      by the fungus. However, it was a not a major metabolite for horse and fungus,
      which highlights the importance of performing metabolism studies in the species
      of interest.

PMID- 29334635
TI  - The effect of altitude and climate on the suicide rates in Turkey.
AB  - Suicide is one of the most important public health problems. There was an
      association between suicide and several factors such as psychiatric diseases and
      psychological characteristics, somatic illness, cultural, socioeconomic,
      familial, occupational and individual risk factors. Also, high altitude and
      climatic factors including high temperature, cloudiness, more sunshine and low
      rainfalls were defined as some of these risk factors in the literature. In this
      study, we aimed to investigate correlation between suicide rates and altitudes of
      all cities in Turkey and between suicide rates and climatic factors including
      Rainfall Activity Index, Winter Mean Temperatures, Summer Mean Temperatures and
      Temperature Difference between January and July previously defined by several
      authors in the broad series in Turkey. In Turkey, 29865 suicidal deaths occurred
      in 10 years period between 2006 and 2015. Of them, 21020 (70.4%) were males and
      8845 (29.6%) were females. In this study, we found that high altitude above 1500
      m, winter median temperature lower than -10  degrees C and hard temperature
      changes above 25  degrees C between winter and summer of settlements were
      important factors that affected on female suicide rates appropriate to knowledge
      which defined in previous studies. In conclusion, we suggested that the
      associations among suicide rates with altitudes and climate should be studied in
      wider series obtained from different countries for reaching more reliable
      results.

PMID- 29334636
TI  - Impact of demographic factors on the antidepressant effect: A patient-level data
      analysis from depression trials submitted to the Pharmaceuticals and Medical
      Devices Agency in Japan.
AB  - A substantial and variable placebo response can cause unreliable findings in
      clinical trials designed to demonstrate the efficacy of antidepressants, and the
      high rate of failed trials represents a major obstacle in the development of new
      drugs for major depressive disorder (MDD). However, the influence of demographic
      and symptom factors on the antidepressant effect remains to be established. The
      purpose of this study was to estimate the magnitude of this influence. A patient
      level meta-analysis of data from double-blind, randomized, placebo-controlled
      trials involving the use of antidepressants for adults with MDD was performed.
      Data from five confirmatory trials evaluating the efficacy of four
      antidepressants that were submitted to the Pharmaceuticals and Medical Devices
      Agency (PMDA) to support new drug applications were pooled (n = 1898). The change
      in the total score of 17-item Hamilton Depression Rating Scale (HDRS17) was the
      primary outcome of interest in our analysis. The changes in the total HDRS17
      score in both the antidepressant medication group (ADM) and the placebo group
      (PBO) increased in relation to baseline symptom severity. Among older patients
      and those with a history of prior treatment with antidepressants, the changes in
      the total HDRS17 score decreased in ADM and remained static in PBO. There were no
      notable clinical symptoms that influenced the change in the total HDRS17 score.
      Baseline symptom severity, participant age and a history of previous treatment
      with antidepressants were suggested as moderators of the antidepressant effect.
      The drug-placebo difference in the estimated changes as a function of baseline
      symptom severity varied depending on the regression models used, and further
      studies are required to investigate appropriate models.

PMID- 29334637
TI  - Contamination characteristics and source apportionment of heavy metals in topsoil
      from an area in Xi'an city, China.
AB  - As soil-extractable elements potentially pose ecological and health risks,
      identifying their contamination characteristics and sources is crucial.
      Therefore, to understand topsoil trace elements in the urban ring zone from the
      Second Ring Road to the Third Ring of Xi'an city in China, we determined the
      concentrations of Zn, Co, V, As, Cu, Mn, Ba, Ni and Pb, and analyzed the sources
      of the contamination. The results showed that the individual pollution indices of
      Pb, Co, Cu, Zn, Ba, Ni, Mn, As, and V were 1.79, 1.48, 1.41, 1.33, 1.20, 1.07,
      1.04, 0.99, and 0.99, respectively. Evaluation with the aid of the pollution load
      index (PLI) indicated slight soil contamination by these elements in the study
      area. Using the positive matrix factorization (PMF) method, we identified four
      sources of contamination, namely (1) a natural source, (2) traffic emission
      source, (3) industrial emission source, and (4) mixed source. PMF is an effective
      tool for source apportionment of heavy metals in topsoil. The contribution rates
      of the natural source, traffic source, mixed source, and industrial source to the
      heavy metal contamination were specified as 25.04%, 24.71%, 24.99%, and 25.26%,
      respectively. Considering the above, any attempt to reduce the soil environmental
      cost of urban development, has to take into account the heavy metal contamination
      of the topsoil from industries, traffic, and other activities.

PMID- 29334638
TI  - The effectiveness of physical exercise on cognitive and psychological outcomes in
      individuals with mild cognitive impairment: A systematic review and meta
      analysis.
AB  - OBJECTIVE: Individuals with mild cognitive impairment (MCI) are at high risk for
      developing dementia. Physical exercise is a promising intervention for cognitive
      decline. Systematic reviews regarding the effects of physical exercise on
      cognitive and psychological outcomes among MCI patients are limited, and a
      systematic review exploring the effects of exercise modalities on the results has
      not been conducted. This study evaluated the effects of physical exercise on
      cognitive and psychological outcomes for MCI patients and attempted to identify
      which specific modality of exercise is more effective. DESIGN: Systematic review
      and meta-analysis. DATA SOURCES: A systematic search of Medline, CINAHL, EMBASE,
      PsycINFO, SPORTDiscus, and the China National Knowledge Infrastructure was
      performed. REVIEW METHODS: Two reviewers independently assessed the study quality
      using the Effective Public Health Practice Project Quality Assessment Tool. Meta
      analysis was conducted when data were available, with further subgroup analyses
      for exercise types. A series of sensitivity analyses were conducted to explore
      the influence of study quality and control types on the primary outcome. A
      narrative analysis was performed when statistical synthesis was inappropriate.
      RESULTS: Eleven studies met the inclusion criteria. The exercise interventions
      can be classified into three types: (a) aerobic exercise, (b) resistance
      exercise, and (c) multi-modal exercise. Results showed that physical exercise had
      beneficial effects for global cognition [standard mean difference (SMD) = 0.30,
      95% confidence interval (CI): 0.10-0.49, p = 0.002]. Further subgroup analysis
      demonstrated that aerobic exercise programmes are consistently associated with
      medium effect size (SMD: 0.54-0.58). However, the effects of physical exercise on
      domain-specific cognitive function and psychological outcomes in MCI patients
      remain inconclusive. Results of sensitivity analysis indicated that types of
      control exert influence on the outcomes. CONCLUSIONS: Physical exercise, aerobic
      exercise in particular, benefits global cognition in MCI patients. The evidence
      of physical exercise on domain-specific cognitive function and psychological
      outcomes remains unclear, more trials with rigorous study design are necessary to
      provide the evidence.

PMID- 29334639
TI  - Vestibular schwannoma and hearing preservation: Usefulness of level specific CE
      Chirp ABR monitoring. A retrospective study on 25 cases with preoperative
      socially useful hearing.
AB  - BACKGROUND AND OBJECTIVES: Decision-making regarding the therapy of vestibular
      schwannoma (VS) changed over the last decades, during which curative microsurgery
      has been promoted. Goals of VS microsurgery are: extensive resection, facial
      nerve (FN) preservation and, in selected cases, hearing preservation (HP). The
      aim of this study is to evaluate postoperative HP with reference to tumor size in
      patients operated on with Level Specific (LS)-CE-Chirp(r) ABR monitoring.
      PATIENTS AND METHODS: Twentyfive consecutive patients with socially useful
      hearing (SUH) underwent VS microneurosurgery by retrosigmoid (RS) approach.
      Selection criteria were: pure tone audiogram <50dB loss and speech discrimination
      score >50% (50/50 criterion; AAO-HNS class A-B). In relation to maximum diameter,
      we identified 2 size-groups: A) <=2cm (13 cases); B) >2cm (12 cases). HP attempt
      was assisted by intraoperative ABR evoked by LS CE-Chirp(r) acoustic stimuli.
      RESULTS: Mean age was 44,3 years (20-64); average maximum diameter 2,04cm (8
      40mm). Total and nearly-total (>95%) resection was possible in all. Mortality and
      major morbidity were zero. In all, FN was anatomically and functionally
      preserved; in 10 an incomplete FN deficit (House-Brackmann II and III) was
      followed by complete recovery (House-Brackmann I). SUH preservation rate was 52%,
      with significant differences in relation to size: 61,5% group A and 41,7% group B
      (p = 0,014). Postoperative AAO-HNS C (serviceable) hearing was observed in 36%,
      deafness in 12%. CONCLUSION: Microsurgery represents a valid therapeutic option
      for small growing VS with SUH. Our data confirm that RS removal of VS with
      intraoperative ABR monitoring allows good rate of SUH preservation, especially if
      maximum diameter does not exceed 2cm. LS-CE-Chirp ABR represent a safe and
      effective method for monitoring cochlear nerve, with fast and clear
      intraoperative neurophysiological feedback.

PMID- 29334640
TI  - Not single brain areas but a network is involved in language: Applications in
      presurgical planning.
AB  - OBJECTIVES: Language is an important human function, and is a determinant of the
      quality of life. In conditions such as brain lesions, disruption of the language
      function may occur, and lesion resection is a solution for that. Presurgical
      planning to determine the language-related brain areas would enhance the chances
      of language preservation after the operation; however, availability of a
      normative language template is essential. PATIENTS AND METHODS: In this study,
      using data from 60 young individuals who were meticulously checked for mental and
      physical health, and using fMRI and robust imaging and data analysis methods,
      functional brain maps for the language production, perception and semantic were
      produced. RESULTS: The obtained templates showed that the language function
      should be considered as the product of the collaboration of a network of brain
      regions, instead of considering only few brain areas to be involved in that.
      CONCLUSION: This study has important clinical applications, and extends our
      knowledge on the neuroanatomy of the language function.

PMID- 29334641
TI  - Do clinically anxious children cluster according to their expression of factors
      that maintain child anxiety?
AB  - BACKGROUND: Cognitive Behaviour Therapy (CBT) is an effective treatment for
      childhood anxiety disorders, yet a significant proportion of children do not
      benefit from it. CBT for child anxiety disorders typically includes a range of
      strategies that may not all be applicable for all affected children. This study
      explored whether there are distinct subgroups of children with anxiety disorders
      who are characterized by their responses to measures of the key mechanisms that
      are targeted in CBT (i.e. interpretation bias, perceived control, avoidance,
      physiological arousal, and social communication). METHODS: 379 clinically anxious
      children (7-12 years) provided indices of threat interpretation, perceived
      control, expected negative emotions and avoidance and measures of heart rate
      recovery following a speech task. Parents also reported on their children's
      social communication difficulties using the Social Communication Questionnaire
      (SCQ). RESULTS: Latent profile analysis identified three groups, reflecting (i)
      'Typically anxious' (the majority of the sample and more likely to have
      Generalized anxiety disorder); (ii) 'social difficulties' (characterized by high
      SCQ and more likely to have social anxiety disorder and be male); (iii)
      'Avoidant' (characterized by low threat interpretation but high avoidance and low
      perceived control). LIMITATIONS: Some measures may have been influenced by
      confounding variables (e.g. physical variability in heart rate recovery). Sample
      characteristics of the group may limit the generalizability of the results.
      CONCLUSIONS: Clinically anxious children appear to fall in to subgroups that
      might benefit from more targeted treatments that focus on specific maintenance
      factors. Treatment studies are now required to establish whether this approach
      would lead to more effective and efficient treatments.

PMID- 29334642
TI  - Examining the latent structure mechanisms for comorbid posttraumatic stress
      disorder and major depressive disorder.
AB  - BACKGROUND: Posttraumatic stress disorder (PTSD) is a complex psychiatric illness
      that can be difficult to diagnose, due in part to its comorbidity with major
      depressive disorder (MDD). Given that researchers have found no difference in
      prevalence rates of PTSD and MDD after accounting for overlapping symptoms, the
      latent structures of PTSD and MDD may account for the high comorbidity. In
      particular, the PTSD Negative Alterations in Cognition and Mood (NACM) and
      Hyperarousal factors have been characterized as non-specific to PTSD. Therefore,
      we compared the factor structures of the Diagnostic and Statistical Manual of
      Mental Disorders, 5thedition (DSM-5) PTSD and MDD and examined the mediating role
      of the PTSD NACM and Hyperarousal factors on the relationship between MDD and
      PTSD symptom severity. METHODS: Participants included 598 trauma-exposed veterans
      (Mage = 48.39, 89% male) who completed symptom self-report measures of DSM-5 PTSD
      and MDD. RESULTS: Confirmatory factor analyses indicated an adequate-fitting four
      factor DSM-5 PTSD model and two-factor MDD model. Compared to other PTSD factors,
      the PTSD NACM factor had the strongest relationship with the MDD Affective
      factor, and the PTSD NACM and Hyperarousal factors had the strongest association
      with the MDD Somatic factor. Further, the PTSD NACM factor explained the
      relationship between MDD factors and PTSD symptom severity. More Affective and
      Somatic depression was related to more NACM symptoms, which in turn were related
      to increased severity of PTSD. LIMITATIONS: Limitations include the reliance on
      self-report measures and the use of a treatment-seeking, trauma-exposed veteran
      sample which may not generalize to other populations. CONCLUSIONS: Implications
      concerning the shared somatic complaints and psychological distress in the
      comorbidity of PTSD and MDD are discussed.

PMID- 29334643
TI  - Longitudinal determinants of depression among World Trade Center Health Registry
      enrollees, 14-15 years after the 9/11 attacks.
AB  - BACKGROUND: Exposure to the September 11, 2001 (9/11) terrorist attacks has been
      found to be associated with posttraumatic stress disorder (PTSD) and comorbid
      PTSD and depression up to 10-11 years post-disaster. However, little is known
      about the longitudinal predictors of mental health conditions over time. METHODS:
      We examined longitudinal determinants of depression within strata of PTSD among
      21,258 enrollees of the World Trade Center Health Registry who completed four
      questionnaires over 14 years of follow-up (Wave 1 in 2003-04; Wave 2 in 2005-06;
      Wave 3 in 2011-12; and Wave 4 in 2015-16). PTSD status was measured using the
      PTSD checklist on all four waves and defined as a score of >= 44; depression was
      assessed using the 8-item Patient Health Questionnaire at Waves 3 and 4 and
      defined as a score of >= 10. RESULTS: Across Waves 3 and 4, 18.6% experienced
      depression, and it was more common among those who ever had PTSD (56.1%) compared
      with those who had not (5.6%). Across PTSD strata, predictors of depression
      included low income, unemployment, low social integration and support, post-9/11
      traumatic life events, and chronic physical illness. These factors also decreased
      the likelihood of recovering from depression. LIMITATIONS: Depression symptoms
      were not measured at Waves 1 and 2; data was self-reported. CONCLUSIONS: These
      findings highlight the substantial burden of depression in a trauma-exposed
      population 14-15 years post-disaster, especially among those with PTSD. Similar
      life stressors predicted the course of depression among those with and without
      PTSD which may inform public health and clinical interventions.

PMID- 29334644
TI  - Predictors of remission from probable depression among Hong Kong adolescents - A
      large-scale longitudinal study.
AB  - BACKGROUND: This study investigated the incidence of remission from probable
      depression among adolescents in Hong Kong. Remissions were defined as having
      Center for Epidemiological Studies Depression Scale (CESD) scores changed from
      >=16 at baseline to <16 over the 12-month follow-up period. The study tested the
      predictors of remissions, including perceived changes in family support, self
      efficacy, self-esteem, positive affect, negative events, social anxiety, and
      loneliness. METHODS: The study surveyed 9666 secondary school students and
      identified 5487 (57%) students with probable depression in Hong Kong. A
      questionnaire assessing the levels of the aforementioned variables was completed
      at baseline and at the 12-month follow-up. RESULTS: Among participants with
      probable depression at baseline, 23.2% remitted from depression at follow-up.
      Remissions were more common among males than females. Univariate logistic
      regression showed that perceived changes in all the aforementioned variables
      significantly predicted remission for both males and females. The same is true
      for most of these variables when they were entered together into multiple
      logistic regression models (with and without controlling for baseline CESD
      scores), except for family support in the female model and self-efficacy in both
      male and female models. LIMITATIONS: Limitations include potential self-report
      bias and only one follow-up observation over time. The design treats cases of
      probable mild to severe depression as a single group (CESD>=16). CONCLUSIONS: The
      findings are potentially useful for designing and guiding related intervention
      programs. Results highlight the importance of long-term follow-up of those
      screened as probable depression to understand the course of changes in levels of
      depression.

PMID- 29334645
TI  - Co-morbid depressive disorder is associated with better neurocognitive
      performance in first episode schizophrenia spectrum.
AB  - BACKGROUND: Both major depressive disorder (MDD) and first episode schizophrenia
      spectrum (FES) are associated with significant neurocognitive deficits. However,
      it remains unclear whether the neurocognitive deficits in individuals with FES
      are more severe if there is comorbid depressive disorder. The aim of this study
      was to compare the neurocognitive profiles between those with and without full
      threshold depressive disorder in FES. METHOD: This study involved secondary
      analysis of baseline data from a randomized controlled trial of vocational
      intervention for young people with first-episode psychosis (N = 82; age range: 15
      25 years). RESULTS: Those with full-threshold depressive disorder (n = 24) had
      significantly better information processing speed than those without full
      threshold depressive disorder. Severity of depressive symptoms was also
      associated with better information processing speed. LIMITATIONS: In additional
      to the cross-sectional design, limitations of this study include the absence of
      assessing insight as a potential mediator. CONCLUSIONS: After the first psychotic
      episode, it could be speculated that those with better information processing
      speed may be more likely to develop full-threshold depressive disorder, as their
      ability to efficiently process information may allow them to be more aware of
      their situations and environments, and consequently to have greater insight into
      the devastating consequences of FES. Such novel findings support the examination
      of full-threshold depressive disorder in relation to neurocognitive performance
      across illness phases in future work.

PMID- 29334646
TI  - 17beta-estradiol improves the efficacy of exploited autologous bone marrow
      derived mesenchymal stem cells in non-union radial defect healing: A rabbit
      model.
AB  - Exploiting mesenchymal stem cells (MSCs) appears to be an appealing alternative
      to the traditional clinical approach in the treatment of non-union bone defects.
      It has been shown that 17beta-estradiol improves the osteogenesis and
      proliferation potential of the MSCs via estrogen receptors. We investigated the
      effect of 17beta-estradiol on exploiting autologous BMSCs (bone marrow-derived
      MSCs) for the purpose of healing of radial non-union segmental defect in rabbit.
      Twenty rabbits were divided into 4 experimental groups: 1. Control group; 2. MSC
      treatment group; 3. 17beta-estradiol (E2) treatment group; and 4. E2+MSC
      treatment group. Isolated BMSCs were seeded in a critical-sized defect on radial
      mid-diaphysis that was filled with autologous fibrin clot differently in 4
      groups: 1. intact fibrin clot (control); 2. Fibrin clot containing MSCs; 3.
      Estradiol; and 4. E2 and MSCs. Defect healing was assessed by radiological (week
      0, 2, 4, 6, 8 and 10) and histopathological evaluation (week 10). Radiological
      evaluation data demonstrated that quantities for the E2+MSC group were
      significantly the greatest in comparison with the other groups at week 4 to 10
      inclusive. Moreover, Histopathological evaluation indicated that the E2+MSC group
      had the highest score which was significantly greater than the E2 group and the
      control group (P<0.05). In-vivo application of in situ 17beta-estradiol provides
      the seeded BMSCs with improved osteogenic capacity in tandem with an accelerated
      rate of bone healing. This obviously more qualified approach that yields in a
      shorter time appears to be promising for the future cell-based clinical
      treatments of the non-union bone fractures. Exploiting mesenchymal stem cells
      (MSCs) appears to be an appealing alternative to the traditional clinical
      approach in the treatment of non-union bone defects. It has been shown that
      17beta-estradiol improves the osteogenesis and proliferation potential of the
      MSCs via estrogen receptors. We investigated the effect of 17beta-estradiol on
      exploiting autologous BMSCs (bone marrow-derived MSCs) for the purpose of healing
      of radial non-union segmental defect in rabbit. Twenty rabbits were divided into
      4 experimental groups: 1. Control group; 2. MSC treatment group; 3. 17beta
      estradiol (E2) treatment group; and 4. E2+MSC treatment group. Isolated BMSCs
      were seeded in a critical-sized defect on the radial mid-diaphysis that was
      filled with autologous fibrin clot differently in 4 groups: 1. intact fibrin clot
      (control); 2. Fibrin clot containing MSCs; 3. Estradiol; and 4. E2 and MSCs.
      Defect healing was assessed by radiological (week 0, 2, 4, 6, 8 and 10) and
      histopathological evaluation (week 10). Radiological evaluation data demonstrated
      that quantities for the E2+MSC group were significantly the greatest in
      comparison with the other groups at week 4 to 10 inclusive. Moreover,
      Histopathological evaluation indicated that the E2+MSC group had the highest
      score which was significantly greater than the E2 group and the control group
      (P<0.05). In-vivo application of in situ 17beta-estradiol provides the seeded
      BMSCs with improved osteogenic capacity in tandem with an accelerated rate of
      bone healing. This obviously more efficient approach that yields in a shorter
      time appears to be promising for future cell-based clinical treatments of the non
      union bone fractures.

PMID- 29334647
TI  - Time-resolved decoding of planned delayed and immediate prehension movements.
AB  - Different contexts require us either to react immediately, or to delay (or
      suppress) a planned movement. Previous studies that aimed at decoding movement
      plans typically dissociated movement preparation and execution by means of
      delayed-movement paradigms. Here we asked whether these results can be
      generalized to the planning and execution of immediate movements. To directly
      compare delayed, non-delayed, and suppressed reaching and grasping movements, we
      used a slow event-related functional magnetic resonance imaging (fMRI) design. To
      examine how neural representations evolved throughout movement planning,
      execution, and suppression, we performed time-resolved multivariate pattern
      analysis (MVPA). During the planning phase, we were able to decode upcoming
      reaching and grasping movements in contralateral parietal and premotor areas.
      During the execution phase, we were able to decode movements in a widespread
      bilateral network of motor, premotor, and somatosensory areas. Moreover, we
      obtained significant decoding across delayed and non-delayed movement plans in
      contralateral primary motor cortex. Our results demonstrate the feasibility of
      time-resolved MVPA and provide new insights into the dynamics of the prehension
      network, suggesting early neural representations of movement plans in the primary
      motor cortex that are shared between delayed and non-delayed contexts.

PMID- 29334648
TI  - Using mass struvite precipitation to remove recalcitrant nutrients and
      micropollutants from anaerobic digestion dewatering centrate.
AB  - The primary objective of this research was to remove recalcitrant nutrients from
      anaerobically digested sludge dewatering centrate. A struvite precipitation
      methodology is proposed where salt crystals are encouraged to ballast colloidal
      particles through heterogeneous nucleation and subsequent crystal growth. The
      secondary objective was to assess presence of micropollutants in precipitates.
      Four biologically unique dewatering centrates were used to test the precipitation
      methodology on the variety of anaerobic digester configurations that can be
      expected from municipal wastewater treatment plant. The effect of digestion
      sludge retention time (2 day, 20 day) and digestion temperature (35  degrees C,
      55  degrees C) on the removal of dissolved unreactive phosphorus (P) and nitrogen
      (N) was monitored. Averaged across all four centrates, the precipitation
      methodology resulted in dissolved unreactive P and N removal of 82.4% and 66.6%,
      respectively. Antimicrobial contaminants (triclosan, triclocarban) were observed
      in the precipitates at minute concentrations (<18 ng/g-dry solids). Therefore,
      mass struvite precipitation can provide a means of recalcitrant nutrient
      treatment and reactive nutrient recovery without the micropollutant burden of
      biosolids land application.

PMID- 29334649
TI  - Determining variables that influence the phosphorus content of waste
      stabilization pond algae.
AB  - Waste stabilization ponds (WSP) are one of the most common forms of wastewater
      treatment for smaller communities globally, but have poor phosphorus removal. It
      is known that WSP algae can accumulate polyphosphate within their cells in excess
      of that needed for cell function. If polyphosphate accumulation could be
      triggered at the higher range of WSP cell concentrations, phosphorus removal from
      domestic wastewater could be significantly improved. However, this phenomenon is
      sporadic and still not fully understood. With a view of building a fundamental
      understanding to underpin the engineering of a new phosphorus removal process,
      this paper examines eight previously untested variables that may influence the
      cellular phosphorus content of WSP biomass. Although calcium, magnesium, and
      potassium are key constituents of polyphosphate granules, the concentrations
      tested were not limiting to polyphosphate accumulation. While literature also
      pointed to inoculum characteristics as potentially having an impact, no
      significance was found in this research. Conversely, three important new triggers
      where identified that significantly (90% confidence) affected the cellular
      phosphorus content of WSP biomass. An increase in cellular phosphorus content was
      triggered by decreasing the organic load, or allowing the pH to increase as
      compared to pH control. By contrast, the presence of mixing decreased the
      phosphorus content of the WSP biomass.

PMID- 29334650
TI  - Environmentally relevant concentrations of glibenclamide induce oxidative stress
      in common carp (Cyprinus carpio).
AB  - The hypoglycemic pharmaceutical glibenclamide (GLB) is widely used around the
      world. This medication is released into the environment by municipal, hospital
      and industrial wastewater discharges. Although there are reports of its
      environmental occurrence in the scientific literature, toxicity studies on
      aquatic species of commercial interest such as the common carp Cyprinus carpio
      are scarce. The present study aimed to evaluate the oxidative stress induced on
      C. carpio by environmentally relevant concentrations of GLB. Biomarkers of
      oxidative damage such as hydroperoxide content, lipid peroxidation and protein
      carbonyl content were evaluated as well as the activity of the antioxidant
      enzymes superoxide dismutase and catalase. The concentration of GLB was
      determined in water as well as in gill, liver, muscle, brain and blood of carp at
      12, 24, 48, 72 and 96 h. The findings obtained in the study prove that GLB
      induces increases in biomarkers of oxidative damage and antioxidant enzyme
      activity in the teleost C. carpio, that this response is not concentration
      dependent and that the organs evaluated bioconcentrate this hypoglycemic agent.
      These findings permit us to conclude that the presence of GLB in water bodies
      represents a risk for aquatic species.

PMID- 29334652
TI  - Insight into the expression variation of metal-responsive genes in the seedling
      of date palm (Phoenix dactylifera).
AB  - Phytochelatin synthase and metallothionein gene expressions were monitored via
      qPCR in order to investigate the molecular mechanisms involved in Cd and Cr
      detoxification in date palm (Phoenix dactylifera). A specific reference gene
      validation procedure using BestKeeper, NormFinder and geNorm programs allowed
      selection of the three most stable reference genes in a context of Cd or Cr
      contamination among six reference gene candidates, namely elongation factor
      alpha1, actin, aldehyde dehydrogenase, SAND family, tubulin 6 and TaTa box
      binding protein. Phytochelatin synthase (pcs) and metallothionein (mt) encoding
      gene expression were induced from the first days of exposure. At low Cd stress
      (0.02 mM), genes were still up-regulated until 60th day of exposure. At the
      highest metal concentrations, however, pcs and mt gene expressions decreased. pcs
      encoding gene was significantly up-regulated under Cr exposure, and was more
      responsive to increasing Cr concentration than mt encoding gene. Moreover,
      exposure to Cd or Cr influenced clearly seed germination and hypocotyls
      elongation. Thus, the results have proved that both analyzed genes participate in
      metal detoxification and their expression is regulated at transcriptional level
      in date palm subjected to Cr and Cd stress. Consequently, variations of
      expression of mt and pcs genes may serve as early-warning biomarkers of metal
      stress in this species.

PMID- 29334651
TI  - Effects of perinatal fluoride exposure on the expressions of miR-124 and miR-132
      in hippocampus of mouse pups.
AB  - To investigate the effects of perinatal fluoride exposure on learning and memory
      ability of mouse offspring, ICR female mice were received different doses of
      sodium fluoride (0, 25, 50, 100 mg/L NaF) from pregnant day 7 to lactational day
      21. Pups were exposed to fluoride through the cord blood and breast milk. Open
      field test showed that compared to the control group, perinatal fluoride exposure
      significantly decreased the number of entries into the center zone in 100 mg/L
      NaF group. In the eight-arm maze test, the number of working memory errors,
      reference memory errors, and the total arm entries were significantly increased
      in fluoride treatment groups, compared to the control group. Additionally, 100
      mg/L NaF significantly elevated the expression levels of miR-124, miR-132, and
      DiGeorge syndrome chromosomal region 8 (DGCR8) in hippocampus of mouse pups at
      postnatal day (PND) 21. Contrarily, methyl CpG binding protein 2 (MeCP2) were
      dramatically reduced in 50 and 100 mg/L NaF groups, while cAMP-response element
      binding protein (CREB) mRNA level was significantly decreased in all fluoride
      groups. These findings suggested that the impairment of learning and memory in
      mouse offspring induced by perinatal fluoride exposure may partly result from the
      enhanced miR-124 and miR-132 and the alterations of their target genes.

PMID- 29334653
TI  - Depletion study, withdrawal period calculation and bioaccumulation of
      sulfamethazine in tilapia (Oreochromis niloticus) treated with medicated feed.
AB  - The residue depletion of sulfamethazine (SMZ) was evaluated in tilapia
      (Oreochromis niloticus) after 11 days of administration of medicated feed
      containing SMZ, at the dose of 422 mg/kg body weight (bw). The determination of
      SMZ in feed and tilapia fillet was carried out using the QuEChERS approach for
      sample preparation, and high performance liquid chromatography with diode array
      detector (HPLC-DAD) and ultra-high performance liquid chromatography-quadrupole
      time-of-flight mass spectrometry (UPLC-QToF-MS) for quantitation, respectively.
      Both methods were validated based on international and Brazilian guidelines and
      shown to be suitable for the intended purposes. The withdrawal period to reach
      the maximum residue level (MRL) of 100 MUg/kg, according to the European Union
      (EU) legislative framework to all substances belonging to the sulfonamide (SA)
      group (EU, 2010), was 10 days (260  degrees C-day). After treatment, the maximum
      level of SMZ accumulation in the tilapia muscle was 1.6 mg/kg. SMZ was shown to
      be quickly excreted by tilapia. Thus, considering the acceptable daily intake of
      SMZ established by the Codex Commission (0-0.05 mg/kg bw), and a factor of 5
      times the upper amount of fish consumption in Brazil (38 kg/year), this study
      showed that there is a low risk of adverse effects to consumers. This study
      offers subsidies not only for the establishment of public policies with regard to
      the use of veterinary drugs currently not allowed in a country by their legal
      legislative framework for fish farming, but also to fish producers for the proper
      handling to ensure safe fish fillets.

PMID- 29334655
TI  - How yeast coordinates metabolism, growth and division.
AB  - All cells, especially single cell organisms, need to adapt their metabolism,
      growth and division coordinately to the available nutrients. This coordination is
      mediated by extensive cross-talk between nutrient signaling, metabolism, growth,
      and the cell division cycle, which is only gradually being uncovered: Nutrient
      signaling not only controls entry into the cell cycle at the G1/S transition, but
      all phases of the cell cycle. Metabolites are even sensed directly by cell cycle
      regulators to prevent cell cycle progression in absence of sufficient metabolic
      fluxes. In turn, cell cycle regulators such as the cyclin-dependent kinase
      directly control metabolic fluxes during cell cycle progression. In this review,
      I highlight some recent advances in our understanding of how metabolism and the
      cell division cycle are coordinated in the model organism Saccharomyces
      cerevisiae.

PMID- 29334654
TI  - PHBV polymer supported denitrification system efficiently treated high nitrate
      concentration wastewater: Denitrification performance, microbial community
      structure evolution and key denitrifying bacteria.
AB  - Biodegradable polymer supported denitrification (BPD) system shows good
      denitrification performance for the wastewater with low nitrate concentrations.
      In this study, a BPD system using Poly (3-hydroxybutyrate-co-3-hydroxyvalerate)
      (PHBV) polymer as carbon source was developed to treat the wastewater with high
      nitrate concentrations. The denitrification performance, utilization ratio of
      PHBV polymers, and microbial community structure evolution and key denitrifying
      bacteria were comprehensively studied. Results indicated that an average nitrate
      removal efficiency of 99% could be achieved with an influent NO3--N concentration
      of 100 mg L-1 and a hydraulic retention time (HRT) of 7.25 h. Mass balance model
      predicted that 80% of the PHBV polymers were consumed by denitrifying bacteria,
      close to 72% consumption in real condition, suggesting the model might be useful
      for PHBV polymers management in BPD system. Further, the bacterial community
      structures varied along the bioreactor profile, which closely linked to the
      concentration profiles of nitrate and ammonia. Metatranscriptomic analysis
      identified the key denitrifying bacteria as Comamonas, Acidovorax and
      Dechloromonas. The PHBV supported denitrification system developed in this study
      shows potential for removal of high concentration of nitrate from wastewater.

PMID- 29334656
TI  - Activated protein C suppresses osteoclast differentiation via endothelial protein
      C receptor, protease-activated receptor-1, sphingosine 1-phosphate receptor, and
      apolipoprotein E receptor 2.
AB  - INTRODUCTION: Bone remodeling relies on a delicate balance between formation and
      resorption of bone tissues, processes in which bone-forming osteoblasts and bone
      resorbing osteoclasts play central roles. Recently, we reported that
      anticoagulant activated protein C (APC) promotes osteoblast proliferation, but
      the role of the blood coagulation system in bone remodeling remains unclear. In
      this study, to further elucidate the relationship between bone remodeling and
      blood coagulation, we investigated the effect of APC on osteoclast
      differentiation. MATERIALS AND METHODS: Normal human osteoclast precursor cells
      were cultured in their growth medium including soluble RANKL, M-CSF, and FBS, and
      on days 4 and 7, the culture medium was replaced with the same medium containing
      various concentrations of APC, protein C (PC), sphingosine 1-phosphate (S1P)
      receptor agonist, FTY720, or APC+various substances without FBS. On day 8, TRAP
      positive multinucleated cells (>=3 nuclei) were counted manually using a light
      microscope. The effects of APC on NF-kappaB and NFATc1 activation were evaluated
      using specific ELISA. RESULTS: APC suppressed RANKL-induced osteoclast
      differentiation, and this APC-induced suppression of osteoclast differentiation
      was inhibited by zymogen protein C and aprotinin, a serine protease inhibitor.
      Immunohistochemistry and RT-PCR analyses suggested that endothelial protein C
      receptor (EPCR) and protease-activated receptor-1 (PAR-1) were expressed in
      osteoclast precursor cells and osteoclasts. Both anti-PAR-1 antibody and anti
      EPCR antibody (RCR-252), which blocks APC binding to EPCR, inhibited the APC
      induced suppression of osteoclast differentiation. FTY720 had no effect on
      osteoclast differentiation. However, FTY 720 and S1P receptor antagonist, VP
      23019, inhibited the APC-induced suppression of osteoclast differentiation. On
      the other hand, recombinant soluble human ApoER2 and anti-human ApoER2 inhibited
      the APC-induced suppression of osteoclast differentiation. Further, APC had no
      effect on NF-kappaB and NFATc1 activation. CONCLUSIONS: APC suppresses human
      osteoclast differentiation mainly by inhibiting the formation of multinucleated
      cells via EPCR, PAR-1, S1P receptor, and ApoER2 in a manner that depends on APC
      protease activity.

PMID- 29334657
TI  - Relationship of obsessive-compulsive symptoms to clinical variables and cognitive
      functions in individuals at ultra high risk for psychosis.
AB  - Few studies have investigated the relationship between obsessive-compulsive
      symptoms (OCS) and clinical variables, and cognition in individuals at ultra high
      risk (UHR) for psychosis. The aim of this study was to evaluate the frequency of
      OCS and their relationship with clinical variables and cognitive functions in
      individuals at UHR. Eighty-four individuals at UHR for psychosis were
      administered the Brief Psychiatric Rating Scale, the Yale-Brown Obsession
      Compulsion Symptom Check List and, the Calgary Depression Scale for
      Schizophrenia. A cognitive test battery was also applied. We compared the
      clinical, functional, and cognitive parameters of individuals at UHR with and
      without OCS and healthy controls. Thirty-five percent of the UHR sample had at
      least two obsessions/compulsions. The duration of subthreshold psychotic symptoms
      was longer in individuals with OCS. Those who can work/study before first
      presentation were more frequent in OCS-positive group. CDSS scores were higher in
      those with OCS. Compared to controls, OCS-negative group's performance was worse
      in 8 cognitive test items, while OCS-positive group performed worse in only one
      cognitive test item. Our findings suggest that OCS are common in the UHR group.
      OCS might be related to higher level of depression, but better work/study
      performance, and less cognitive deficits in UHR group.

PMID- 29334658
TI  - Contextual determinants of psychopathology. The singularity of attachment as a
      predictor of mental dysfunction.
AB  - The general aim of this research is to evaluate the singular weight of attachment
      relationships in psychopathology, to determine the point to which these
      relationships cannot be subsumed by other variables that are famously related to
      attachment, such as experience of stressful life events, social support, and
      coping styles. 172 people treated in mental health centers provided data related
      to these four aspects and about manifestations of psychopathology. Multiple
      linear regression analyses determined that 51% of the variance in the level of
      symptomatology is explained with six variables: two related to adult attachment
      (fear of rejection and abandonment in romantic relationships, and the degree of
      similarity to the fearful prototype), one related to social support (family
      appreciation), one to life events (overall perceived stress), and two to coping
      style (cognitive restructuring and social withdrawal). Fear of rejection was the
      variable accounting for the most variance. The findings suggest that adult
      attachment is a non-redundant individual factor associated with manifestations of
      psychological dysfunction and highlight the desirability of taking attachment
      history into account in clinical practice.

PMID- 29334659
TI  - Serum zinc levels in acute psychiatric patients: A case series.
AB  - Zinc dysregulation is linked to neuropsychiatric disorders and a beneficial
      response to zinc supplementation has been demonstrated for depression. In this
      case series, we examined serum zinc levels with respect to clinical factors among
      20 acutely ill psychiatric cases admitted to a large urban public hospital. The
      results showed frank clinical zinc insufficiency in a quarter of the subjects.
      Group-wise analyses showed a significant association between reduced serum zinc
      and diagnosis of depression, and reduced serum zinc in those with aggressive,
      assaultive, or violent behaviors. By contrast, relatively elevated zinc levels
      were observed in a subset of psychotic cases on antipsychotics and mood
      stabilizers who had no mood symptoms. In summary, clinical zinc insufficiency was
      common in these acutely admitted psychiatric cases. Zinc supplementation may
      ameliorate symptoms in certain cases and should be considered in treatment
      planning. A separate patient group had elevated zinc levels, which could
      conceivably be pathogenic. Larger studies are needed to confirm and extend this
      pilot data.

PMID- 29334660
TI  - Global proteomic analysis of water buffalo (Bubalus bubalis) saliva at different
      stages of estrous cycle using high throughput mass spectrometry.
AB  - Accurate and efficient detection of estrus is one of the major constraints for
      exploitation of the production potential of buffalo owing to its poor
      manifestation of estrus signs, seasonal differences in expression and higher
      incidences of silent estrus (29%). The current study focused on identification of
      estrus specific candidate proteins in saliva of buffaloes. Estrus was detected
      based on behavioral signs in response to the teaser and changes in reproductive
      organs and confirmed by per-rectal examination, trans-rectal USG of reproductive
      organs, cervico-vaginal mucus characteristics and blood serum progesterone
      estimation. Day of onset of estrus was considered as day 0 and day -3, +3, +10
      were considered as proestrus, metestrus and diestrus stage of the estrous cycle
      respectively. A total of 19 animals and their 38 estrous cycles (two from each)
      were included in this study. Saliva was collected from these animals during
      different stages of estrous cycle. Out of these, 08 animals were selected for
      global proteome analysis of saliva using in-solution digestion and nano-LC-MS/MS.
      A total of 275, 371, 304 and 565 proteins were identified with >=2 peptides
      during proestrus, estrus, metestrus and diestrus stages of estrous cycle. Among
      the identified proteins 31, 62, 32 and 104 proteins were found specific to
      proestrus, estrus, metestrus and diestrus stage of the estrous cycle. Few
      salivary proteins such as Cullin-associated NEDD8-dissociated protein 1, Heat
      shock 70 kDa protein 1A, 17-beta-hydroxysteroid dehydrogenase type 1, Inhibin
      beta A chain, testin were identified as estrus specific and are important for
      estrus physiology. Taken together, these estrus specific proteins could be
      considered as the candidate biomarker for detection and confirmation of estrus in
      buffalo after thorough validation.

PMID- 29334661
TI  - Altered expression of IL-1beta, IL-1RI, IL-1RII, IL-1RA and IL-4 could contribute
      to anovulation and follicular persistence in cattle.
AB  - Cystic ovarian disease (COD) is an important cause of infertility in dairy
      cattle. The main signs of this infertility are ovulation failure and follicular
      persistence. The aim of this study was to examine the expression of the cytokines
      IL-1beta, IL-1RI, IL-1RII, IL-1RA and IL-4 in ovarian follicular structures at
      different times of persistence in a model of follicular persistence induced by
      prolonged administration of progesterone in dairy cows. Protein expression of IL
      1beta, IL-1RI, IL-1RII, IL-1RA and IL-4 was evaluated by immunohistochemistry.
      Additionally, IL-1beta and IL-4 concentrations in follicular fluid and serum were
      determined by ELISA. In granulosa cells, IL1-RII and IL-4 expression was higher
      in follicles with different persistence times than in the control dominant
      follicles. IL-1RA expression was higher in persistent follicles of the P15 group
      (15 days of follicular persistence) than in those of the control group. In theca
      cells, IL-1RII expression was higher in persistent follicles of the P0 group
      (expected time of ovulation) than in dominant follicles from the control group (p
      < .05) and the other persistence groups, whereas IL-4 expression was higher in
      persistent follicles of groups P0 and P15 than in the dominant follicles of the
      control group (p < .05). Differences between serum and follicular fluid within
      each group were detected only in P0 for IL-1beta, and in the control, P10 and P15
      groups for IL-4 (p < .05). These results complement previous results, evidencing
      that early development of COD in cows is concurrent with an altered expression of
      cytokines in different ovarian follicular structures and may contribute to the
      follicular persistence and ovulation failure found in cattle with follicular
      cysts.

PMID- 29334662
TI  - Aqueous extracts of two tropical ethnobotanicals (Tetrapleura tetraptera and
      Quassia undulata) improved spatial and non-spatial working memories in
      scopolamine-induced amnesic rats: Influence of neuronal cholinergic and
      antioxidant systems.
AB  - BACKGROUND: Tetrapleura tetraptera (TT) and Quassia undulata (QU) are two
      predominant tropical ethnobotanicals with various medicinal values but are
      commonly used in folklore for the treatment of mental illness without justifiable
      mechanisms of action. AIM OF THE STUDY: To investigate the effects of aqueous
      extracts from TT fruits and QU leaves on the spatial and non-spatial working
      memory, antioxidant status and activities of neuronal marker enzymes of
      scopolamine-induced amnesic rats and thus, understand the possible mechanism of
      action of these plants. MATERIALS AND METHODS: Fifty-five albino rats were
      divided into eleven groups. Group I (normal rats) received normal saline (p.o),
      Group II-V (normal rats) administered with 50 and 300 mg/kg of each extract group
      VI (induced rats) received 2 mg/kg of scopolamine (i.p.), groups VII-X (induced
      rats) pretreated with 50 and 300 mg/kg of TT and QU extracts (p.o) before
      scopolamine administration, group XI (induced rats) treated with 2.5 mg/kg of
      donepezil. The treatment lasted for 14 days and amnesia was induced by a single
      dose of 2 mg/kg of scopolamine on the last day. Spatial (Y-maze) and non-spatial
      (novel objectect recoginiton test) working memories of the rats were tested.
      Thereafter, the animals were sacrificed and homogenates of isolated brain samples
      were assayed for cholinesterase activity and malondialdehyde (MDA) content. The
      phenolic characterisation of the samples was also carried out using HPLC-DAD
      chromatography. RESULTS: Administration of 2 mg/kg of scopolamine brought about a
      decrease in spatial and non-spatial memory indeces, increase in
      acetylcholinesterase and butyrylcholinesterase activities, as well as increased
      MDA content compared to the control. However, pretreatment with both extracts
      improved both spatial and non-spatial working memories and ameliorated the
      increased enzyme activities and MDA contents. Furthermore, the HPLC-DAD
      characterization of the extracts revealed the presence of p-coumaric acid, rutin,
      catechin, ellagic acid, quercetin, caffeic acid, chlorogenic acid and galic acid.
      CONCLUSION: The ability of the extracts to improved cognitive function and
      ameliorate impairment in cholinergic enzyme activities and antioxidant status in
      scopolamine-induced amnesic rats could help justify the possible neuroprotective
      properties of TT and QU and also explain possible mechanism of action of these
      ethnobotanicals as obtained in folklore medical practices.

PMID- 29334663
TI  - Acute toxicity screening of different extractions, components and constituents of
      Polygonum multiflorum Thunb. on zebrafish (Danio rerio) embryos in vivo.
AB  - Polygonum multiflorum Thunb. has been used widely in East Asia in treatment of
      diseases associated with aging. However, there are many reports referred to the
      toxicity of P. multiflorum, especially for liver adverse reactions. The toxicity
      of it is caused by over dosage or by the herb itself remains unclear. The aim of
      this study was to study the toxicity of different extractions, components and
      constituents of P. multiflorum, which were assessed in zebrafish embryos.
      Firstly, the difference of extracting solvent to the toxicity of P. multiflorum
      was researched to probe the influence of usages to the safety of P. multiflorum.
      The toxicity of 70% EtOH extract is considerably higher than that of other
      extracts. Secondly, 70% EtOH extract was subjected to macroporous resin (DM-8)
      eluting with a gradient of water and EtOH (H2O, 25% EtOH, 40% EtOH and 95% EtOH)
      to give four components (A-D). The toxicity of the component (D) showed higher
      than the other components (A-C). Thus, the component (D) was taken more
      attentions to research. Lastly, study on the chemical constituents of the
      component (D), 27 compounds, including 7 anthraquinones (1-7), 8 stilbenes (8
      15), 7 anthrones (16-22), 3 cinnamic acid amides (23-25), 2 naphthols (26-27)
      were isolated and assessed in zebrafish embryos. Compounds 1-3, 16-22 and 26-27
      showed severe toxicity against the zebrafish embryos while other compounds, such
      as stilbenes, showed no obvious toxicity.

PMID- 29334664
TI  - Methyl dehydroabietate counters high fat diet-induced insulin resistance and
      hepatic steatosis by modulating peroxisome proliferator-activated receptor
      signaling in mice.
AB  - The aim of this study was to investigate the therapeutic effects of methyl
      dehydroabietate (mDA) on adipocyte differentiation in 3T3-L1 preadipocytes and
      obesity characteristics induced by high-fat diet (HFD) in mice. Adipocyte
      differentiation in 3T3-L1 cells was evaluated after 14 days of incubation with
      mDA. mDA enhanced adipocyte differentiation in 3T3-L1 cells. For the in vivo
      evaluation, five-week-old male C57BL/6J mice were fed HFD or normal CE-2 diet
      (control) for eight weeks. During the experimental period, mice were administered
      mDA (50 mg/kg, p.o.) as an olive oil emulsion (containing 10% ethanol), and body
      weights were measured weekly. At the end of the experiment, the mice were
      euthanized after 16 h fasting period, and plasma samples were collected. The
      liver, kidney, and epididymal adipose tissues were collected and weighed. It
      significantly decreased body weight, adipose tissue weight, and plasma levels of
      glucose, insulin, leptin, and pro-inflammatory cytokines compared with that in
      the HFD group, and markedly reduced the impairment in glucose tolerance in obese
      mice. Furthermore, mDA reduced HFD-induced adipocyte hypertrophy and the
      formation of hepatic lipid droplets. Moreover, it induced the expression of
      proliferator-activated receptor alpha (PPARalpha) in the liver and PPARgamma in
      the adipose tissues. Our findings demonstrate that mDA reduces obesity-induced
      glucose and insulin tolerance by inducing PPAR expression.

PMID- 29334665
TI  - I-7ab inhibited the growth of TNBC cells via targeting HDAC3 and promoting the
      acetylation of p53.
AB  - Triple negative breast cancer (TNBC) is a heterogenous disease with high
      aggressive and poor outcome. The lack of biomarkers and targeted therapies makes
      it a challenge for the treatment of TNBC. Histone deacetylase inhibitors (HDACis)
      are emerging as novel anti-tumor agents in many types of human cancers. In this
      study, we found that I-7ab, a novel HDACi, inhibited the cell viability of TNBC
      cells and induced the cell apoptosis. Mechanistically, I-7ab specifically
      decreased the expression of HDAC3 and promoted the acetylation of p53 at both
      Lys373 and Lys382 amino acids. The up-regulated acetylation of p53 promoted the
      transcriptional activity of p53 and induced the expression of p21, which
      consequently caused cell cycle arrest at G1 phase. Administration of I-7ab
      inhibited the colony formation of TNBC cells. Collectively, these results
      indicated I-7ab as a promising anti-cancer agent in the treatment of TNBC.

PMID- 29334666
TI  - Effects of Berberine chloride on the liver of streptozotocin-induced diabetes in
      albino Wistar rats.
AB  - The goal of the present study is to evaluate the effect of Berberine chloride
      (BC) on the liver of streptozotocin (STZ) induced diabetic rat. Diabetic rats
      were treated with BC (50 mg/kg b.w) or glibenclamide (6 mg/kg b.w), daily for 45
      days. After BC treatment in diabetic rats, there was a significant (P < 0.05)
      decline in the levels of hepatic markers, lipid peroxidation markers such as
      lipid hydroperoxides (LOOH) and thiobarbituric acid reactive substances (TBARS),
      and pro-inflammatory mediators like tumor necrosis factor-alpha (TNF-alpha),
      phosphorylated nuclear factor kappa-B-p65 (phospho-NF-kappaB p65), cyclooxygenase
      (COX-2), nitric oxide synthase (iNOS) as well as pro-apoptotic mediators such as
      Bax and cytochrome c. A significant (P < 0.05) increase in hexokinase, glucose-6
      phosphate dehydrogenase, enzymatic antioxidants such as superoxide dismutase
      (SOD), catalase (CAT) and glutathione peroxidase (GPx), and non-enzymatic
      antioxidants such as glutathione (GSH), vitamin E and vitamin C, as well as anti
      apoptotic protein Bcl-2 were observed in the liver of BC treated diabetic rats.
      Thus, from these findings, it can be concluded that the administration of BC
      notably recovered the liver from hyperglycemia induced antioxidant imbalance,
      inflammation and apoptosis as well as rectified the imbalance in carbohydrate
      metabolizing enzymes.

PMID- 29334667
TI  - Lithium, a classic drug in psychiatry, improves nilotinib-mediated antileukemic
      effects.
AB  - Although Tyrosine kinase inhibitors (TKIs) that target Bcr-Abl play a key role in
      Chronic Myeloid Leukemia (CML) therapy, they do not eradicate CML-initiating
      cells, which lead to the emergence of drug resistance. Here we used the lithium,
      a GSK-3 inhibitor, to attempt to potentiate the effects of nilotinib against
      leukemia cells. For this purpose, a K562 leukemia cell line and bone marrow cells
      from untreated Chronic Myeloid Leukemia (CML) patients, prior to any exposure to
      TKIs, were used as a model. Our results demonstrated that the combination of
      lithium + nilotinib (L + N) induced K562-cell death and cleaved caspase-3 when
      compared to lithium or nilotinib alone, accompanied by GSK-3beta phosphorylation
      and Bcr-Abl oncoprotein levels reduction. Interestingly, these events were
      related to autophagy induction, expressed by increased LC3II protein levels in
      the group treated with L + N. Furthermore, the clonogenic capacity of progenitor
      cells from CML patients was drastically reduced by L + N, as well as lithium and
      nilotinib when used separately. The number of cell aggregates (clusters), were
      increased by all treatments (L + N, lithium, and nilotinib). This pioneering
      research has demonstrated that lithium might be of therapeutic value when
      targeting Bcr-Abl cells with nilotinib because it triggers cell death in addition
      to exerting classical antiproliferative effects, opening new perspectives for
      novel target and therapeutic approaches to eradicate CML.

PMID- 29334668
TI  - Lidanpaidu prescription alleviates lipopolysaccharide-induced acute kidney injury
      by suppressing the NF-kappaB signaling pathway.
AB  - The Lidanpaidu Prescription (LDP), a hospital preparation, composed of Chinese
      classical preparations, has been reported to have antiendotoxin, anticoagulant
      and other effects. However, its therapeutic effect on lipopolysaccharide (LPS)
      induced acute kidney injury (AKI) and the mechanisms remain unclear. Therefore,
      we administered LPD pretreatment at different doses to examine the protective
      effects and mechanisms in LPS-induced AKI in mice. The kidney injury induced by
      LPS was assessed by histological examination. ELISA was used to detect the levels
      of inflammatory cytokines. The mRNA expression of the inflammatory genes IKKbeta
      and TNF-alpha in kidney tissues was assessed by RT-PCR. Finally, Western blot was
      performed to assess the NF-kappaB signaling pathway related proteins, and the
      nuclear translocation of NF-kB P65 was detected by immunofluorescence laser
      confocal microscopy. The findings suggested that LDP significantly improved at 48
      h animal survival (66.7%), compared with the LPS group (26.7%), determined by a
      Kaplan-Meier analysis. LDP attenuated the kidney histopathological changes
      induced by LPS and decreased the inflammatory cytokine levels in serum and renal
      tissue. Moreover, LDP markedly inhibited the expression of inflammatory genes and
      suppressed the activation of relevant proteins in the nucleus. In summary, these
      findings suggest that LDP reduces LPS-induced AKI via a mechanism related to the
      suppression of the NF-kappaB signaling pathway.

PMID- 29334669
TI  - Anti-obesity effects of Clausena excavata in high-fat diet-induced obese mice.
AB  - Clausena excavata (C. excavata) has been used as a traditional medicine for the
      treatment of abdominal pain, enteritis, dysentery, and malaria. The present study
      was designed to evaluate the effect of a 50% ethanol extract of C. excavata (ECE)
      on weight loss, adipocyte size, and obesity-related biochemical parameters in
      high-fat diet (HFD)-induced obese mice. After 6 weeks of HFD + ECE
      administration, HFD-induced total fat, subcutaneous fat, and visceral fat were
      evaluated by micro-computed tomography. The serum levels of triglyceride (TG),
      total cholesterol (TCH), high-density lipoprotein (HDL) cholesterol, and low
      density lipoprotein (LDL) cholesterol were evaluated with a biochemical analyzer,
      and leptin and adiponectin levels in the serum were assessed via enzyme-linked
      immunoassay (ELISA). Moreover, adipocyte size and lipid formation in the liver
      were examined. We found that weight gain, epididymal fat pad weight, adipocyte
      size, and lipid formation were markedly attenuated in the livers of HFD-induced
      obese mice treated with ECE. Furthermore, TG, TCH, and leptin decreased in the
      serum, whereas adiponectin increased. In conclusion, our data show that ECE has
      potent anti-obesity activity in vivo and support the development of ECE as a
      potential therapeutic agent for the treatment of obesity.

PMID- 29334670
TI  - Genetic ablation of TRPV1 exacerbates pressure overload-induced cardiac
      hypertrophy.
AB  - Transient receptor potential vanilloid 1 (TRPV1) channels expressed in sensory
      nerves may regulate vascular tone and cardiovascular function via their anti
      inflammatory effects by releasing neuropeptide calcitonin gene-related peptide
      (CGRP). Inflammation plays a role in the progression of cardiac hypertrophy and
      TRPV1 activation may be key to cardiac inflammatory processes. The aim of this
      study was to test the hypothesis that TRPV1 modulates inflammatory processes to
      protect the heart from pressure overload-induced hypertrophy and inflammatory
      responses. Trpv1 knockout (Trpv1-/-) and wild-type (WT) mice were subjected to
      transverse aortic constriction (TAC) or sham operation. Four weeks after TAC, WT
      and Trpv1-/- mice had developed left ventricular (LV) hypertrophy with increased
      LV mass, fibrosis and infiltration of macrophages as well as increased secretion
      of tumor necrosis factor alpha, interleukin-6 from cardiac tissue (all P < 0.05),
      those were higher in Trpv1-/- than in WT mice with TAC (all P < 0.05). In
      addition, decreases of LV ejection fraction and fractional shortening were
      greater in Trpv1-/- than in WT mice (both P < 0.05). Moreover, atrial natriuretic
      peptide level was greater in Trpv1-/- than in WT mice with TAC (P < 0.05).
      Compared to sham control, TAC procedure significantly increased cardiac TRPV1
      expression and CGRP release in WT mice (both P < 0.05), but not in Trpv1-/- mice.
      These results demonstrate that Trpv1 gene deletion results in excessive
      inflammation, exaggerates cardiac hypertrophy, and deteriorates cardiac function
      after TAC, which may be due to abnormal cardiac remodeling and decreased CGRP in
      the absence of TRPV1.

PMID- 29334671
TI  - Glucosamine promotes osteoblast proliferation by modulating autophagy via the
      mammalian target of rapamycin pathway.
AB  - Glucosamine is effective in the treatment of osteoarthritis; however, its effect
      on osteoporosis remains unclear. Decreased activity of osteoblasts is the main
      cause of osteoporosis. Here, we examined the effects of glucosamine on
      osteoblasts. The potential underlying mechanisms were explored. The results
      showed that glucosamine had a biphasic effect on the viability of hFOB1.19
      osteoblasts. At low concentrations (<0.6 mM), glucosamine induced hFOB1.19 cell
      proliferation, whereas at high concentrations (>0.8 mM) it induced apoptosis. The
      autophagy inhibitor 3-methyladenine (3-MA) was used to verify that glucosamine
      modulated hFOB1.19 cell viability via autophagy. The induction of apoptosis by
      high concentrations of glucosamine was significantly exacerbated by 3-MA, whereas
      the promotion of cell proliferation by low concentrations of glucosamine was
      significantly suppressed by 3-MA. Autophagy was examined by western blot
      detection of autophagy-related proteins including LC3, Beclin-1, and SQSTM1/p62
      and by immunofluorescence analysis of autophagosomes. Glucosamine activated
      autophagy in a time- and concentration-dependent manner. Investigation of the
      underlying mechanism showed that glucosamine inhibited the phosphorylation of m
      TOR in a concentration-dependent manner within 48 h, and rapamycin significantly
      inhibited the phosphorylation of m-TOR. These results demonstrated that
      glucosamine promoted hFOB1.19 cell proliferation and increased autophagy by
      inhibiting the m-TOR pathway, suggesting its potential as a therapeutic agent for
      osteoporosis.

PMID- 29334672
TI  - Oxidative and interactive challenge of cadmium and ocean acidification on the
      smooth scallop Flexopecten glaber.
AB  - Ocean acidification (OA) may affect sensitivity of marine organisms to metal
      pollution modulating chemical bioavailability, bioaccumulation and biological
      responsiveness of several cellular pathways. In this study, the smooth scallop
      Flexopecten glaber was exposed to various combinations of reduced pH (pH/pCO2
      7.4/~3000 MUatm) and Cd (20 MUg/L). The analyses on cadmium uptake were
      integrated with those of a wide battery of biomarkers including metallothioneins,
      single antioxidant defenses and total oxyradical scavenging capacity in digestive
      gland and gills, lysosomal membrane stability and onset of genotoxic damage in
      haemocytes. Reduced pH slightly increased concentration of Cd in scallop tissues,
      but no effects were measured in terms of metallothioneins. Induction of some
      antioxidants by Cd and/or low pH in the digestive gland was not reflected in
      variations of the total oxyradical scavenging capacity, while the investigated
      stressors caused a certain inhibition of antioxidants and reduction of the
      scavenging capacity toward peroxyl radical in the gills. Lysosomal membrane
      stability and onset of genotoxic damages showed high sensitivity with possible
      synergistic effects of the investigated factors. The overall results suggest that
      indirect effects of ocean acidification on metal accumulation and toxicity are
      tissue-specific and modulate oxidative balance through different mechanisms.

PMID- 29334673
TI  - Copper bioaccumulation and biokinetic modeling in marine herbivorous fish Siganus
      oramin.
AB  - Marine herbivorous fish directly consume macroalgae, which commonly accumulate
      high levels of trace metals in polluted areas. We proposed that herbivorous fish
      could be better candidates for biomonitoring marine metal pollution than
      carnivorous fish. To date, the trophic transfer of Cu from macroalgae to marine
      herbivorous fish is unclear. In this study, the kinetics of Cu bioaccumulation in
      a widespread marine herbivorous fish, Siganus oramin, were investigated, and
      biokinetic modeling was applied to estimate the Cu levels in the fish sampled
      from different sites and seasons. The results showed that Cu accumulation in the
      fish was linearly correlated to the dietary Cu levels in the different prey
      species, which were proportional to the waterborne Cu concentrations. The Cu
      found in the subcellular trophically available metal fraction (TAM) in the prey
      contributed the largest proportion of accumulated Cu in S. oramin. The dietary
      assimilation efficiencies (AEs) of Cu were 15.56 +/- 1.76%, 13.42 +/- 2.86%, and
      21.36 +/- 1.47% for Ulva lactuca, Gracilaria lemaneiformis and Gracilaria gigas,
      respectively. The calculated waterborne uptake rate constant (ku) of Cu was 0.023
      +/- 0.011 L g-1 d-1, and the efflux rate constant (ke) was 0.055 +/- 0.021 d-1.
      Dietary Cu accounted for 60%-75% of the body Cu in S. oramin, suggesting that
      dietary uptake could be the primary route for Cu bioaccumulation in herbivorous
      fish. The biokinetic model demonstrated that the Cu concentrations in the water
      and fish presented a positive linear relationship, which was in line with our
      field investigation along the coastal areas of South China. Therefore, we
      suggested that S. oramin could be used as a biomonitoring organism for Cu
      pollution in the marine environment. However, the heterogeneities between the
      predicted levels and the measured levels of Cu implied that seasonal changes
      should be taken into account to improve the accuracy of the model.

PMID- 29334674
TI  - Relationship between jumping abilities and skeletal muscle architecture of lower
      limbs in humans: Systematic review and meta-analysis.
AB  - The aim of this study was to examine the influence of skeletal muscle
      architecture (SMA) features measured by 2-D ultrasonography on jumping
      performance in humans. A systematic review and meta-analysis was conducted,
      registry number: CRD42016043602. The scientific literature was systematically
      searched in eight databases, last run on March 14th, 2017. Cross-sectional
      studies focused on the association between SMA features and vertical jumping
      performance were selected. A random-effects model was used to analyze the
      influence of lower-limb SMA and maximal jump height. A total of 11 studies were
      included in the qualitative synthesis and 6 studies were selected for meta
      analysis. 250 correlations were reviewed across studies. The vast majority were
      either not statistically significant (185; 74%), weak or very weak (169; 68%) for
      different jump modalities; counter-movement jump (CMJ), squat jump (SJ), and drop
      jump. There was insufficient data to perform meta-analysis on muscles other than
      vastus lateralis for CMJ and SJ. The meta-analyses did not yield any significant
      association between vastus lateralis SMA and SJ height. Only a significant
      overall association was shown between vastus lateralis thickness and CMJ height
      (summary-r = 0.28; 95% confidence interval (CI) = -0.05 to 0.48; p = .059) for a
      90% CI level. No differences were found between summary-r coefficients for SMA
      parameters and jump height during both jumps (CMJ: chi2 = 2.43; df   = 2; p =
      .30; SJ: chi2 = 0.45; df = 2; p = .80) with a low heterogeneity ratio. Current
      evidence does not suggest a great influence of lower-limb SMA on vertical jumping
      performance in humans.

PMID- 29334675
TI  - Effects of running retraining on biomechanical factors associated with lower limb
      injury.
AB  - Injury risk is an important concern for runners; however, limited evidence exists
      regarding changes to injury risk following running style retraining.
      Biomechanical factors, such as absolute peak free moment, knee abduction impulse,
      peak foot eversion and foot eversion excursion, have been shown to predict lower
      limb injury. The aim of this study was to assess the effects of Pose running
      retraining on biomechanical factors associated with lower limb running injury.
      Twenty uninjured recreational runners were pair-matched based on their five km
      run time performance and randomly assigned to control (n = 10) and intervention
      (three 2-h Pose running retraining sessions) groups (n = 10). Three dimensional
      kinetic and kinematic data were collected from all participants running at
      relative (REL: 1.5 km.h-1 below respiratory compensation point) and absolute
      (ABS: 4.5 m.s-1) speeds. Biomechanical factors associated with lower limb injury,
      as well as selected kinematic variables (to aid interpretation), were assessed.
      Following a six-week, non-coached time-period, all assessments were repeated. No
      changes to the biomechanical factors associated with lower limb injury examined
      in this study were observed (P > .05). Intervention group participants (presented
      as pre- and post-intervention respectively) exhibited an increased foot strike
      index (REL speed: 21.79-42.66%; ESW = 4.73; P = .012 and ABS speed: 22.38-46.98%;
      ESW = 2.83; P = .008), reduced take-off distance (REL speed: -0.35 to -0.32 m;
      ESW = 0.75; P = .012), increased knee flexion at initial contact (REL speed: 
      14.11 to -18.50 degrees ; ESW = -0.88; P = .003), increased ankle dorsiflexion at
      terminal stance (REL speed: -33.61 to -28.35 degrees ; ESW = 1.57; P = .036) and
      reduced stance time (ABS speed: 0.21-0.19 s; ESW = -0.85; P = .018). Finally,
      five km run time did not change (22:04-22:19 min; ESW = 0.07; P = .229). It was
      concluded that following Pose running retraining, retrained participants adopted
      a running style that was different to their normal style without changing
      specific, biomechanical factors associated with lower limb injury or compromising
      performance.

PMID- 29334676
TI  - Statins in the treatment of COPD and asthma-where do we stand?
AB  - Asthma and chronic obstructive pulmonary disease (COPD) are the two most
      prevalent obstructive lung diseases that account for tremendous morbidity and
      mortality throughout the world. These diseases have strong inflammatory
      components, with multiple prior studies showing elevated levels of various
      inflammatory markers and cells in those with COPD and asthma. Therefore, efforts
      to target inflammation in management of these diseases are of great interest.
      Statins, which define a class of drugs that are HMG-CoA inhibitors, are used to
      decrease cholesterol levels and have also been described to have many pleotropic
      effects that include anti-inflammatory and anti-oxidative properties. These
      properties have led to multiple studies looking at the potential use of statins
      in decreasing inflammation in many diseases, including COPD and asthma. This
      review aims to address the current evidence behind the potential use of statins
      in the treatment of asthma and COPD.

PMID- 29334677
TI  - Utilizing journal club to facilitate critical thinking in pre-clinical medical
      students.

PMID- 29334679
TI  - The IL20 Genetic Polymorphism Is Associated with Altered Clinical Outcome in
      Septic Shock.
AB  - BACKGROUND: The IL10 family of genes includes crucial immune regulators. We
      tested the hypothesis that single nucleotide polymorphisms (SNPs) in IL10, IL19,
      IL20, and IL24 of the IL10 family gene cluster alter the clinical outcome of
      septic shock. METHODS: Patients with septic shock (n = 1,193) were genotyped for
      13 tag SNPs of IL10, IL19, IL20, and IL24. IL20 gene expression was measured in
      genotyped lymphoblastoid cells in vitro. Cardiac surgical ICU patients (n = 981)
      were genotyped for IL20 rs2981573 A/G. The primary outcome variable was 28-day
      mortality. RESULTS: Patients with the G allele of IL20 rs2981573 had a
      significantly increased hazard of death over the 28-day period compared to
      patients with the A allele in the septic shock cohort (adjusted hazard ratio
      1.27; 95% confidence interval 1.10-1.47; p = 8.0 * 10-4). Patients with the GG
      genotype had more organ dysfunction (p < 0.05). The GG genotype was associated
      with increased IL20 gene expression in stimulated lymphoblastoid cells in vitro
      (p < 0.05). The cardiac surgical ICU patients with the GG genotype had an
      increased length of ICU stay (p = 0.032). CONCLUSIONS: The GG genotype of IL20
      rs2981573 SNP was associated with increased IL20 gene expression and increased
      adverse outcomes in patients with septic shock and following cardiac surgery.

PMID- 29334678
TI  - Genome Evolution Analysis of Recurrent Testicular Malignant Mesothelioma by Whole
      Genome Sequencing.
AB  - BACKGROUND/AIMS: Malignant mesothelioma of the tunica vaginalis testis is a rare
      and lethal disease. The genomic characteristics and genetic changes of tumor
      cells during the progression of this disease are unknown. METHODS: we performed
      whole-genome sequencing of four successive tumor samples derived from surgery and
      a blood sample in a single patient. RESULTS: All tumors were found to have
      significant C-to-T and T-to-C mutations, and amplification of copy number in
      chromosomes 1 and 12 were notified in all tumor samples. Subclone analysis
      revealed a parallel evolution of the tumor in this patient. We also identified
      some mutations in mesothelioma-associated genes such as KIF25, AHNAK, and PRDM2.
      CONCLUSIONS: The results showed a comprehensive genomic change in malignant
      mesothelioma of the tunica vaginalis testis and provide a better understanding of
      the clonal evolution during tumor recurrence and metastasis.

PMID- 29334680
TI  - Blood Pressure Variability in Acute Ischemic Stroke: Influence of Infarct
      Location in the Insular Cortex.
AB  - BACKGROUND: The aim of this study was to elucidate the influence of insular
      infarction on blood pressure (BP) variability and outcomes according to the
      region of the insular cortex affected. METHODS: A total of 90 patients diagnosed
      with acute unilateral ischemic stroke were registered. The BP variability was
      calculated over 24 h after admission (hyperacute) and for 2-3 days after
      admission (acute). Patients were classified into groups of right and left, and
      then right anterior, right posterior, left anterior, and left posterior insular
      infarction. RESULTS: Patients with insular infarction showed a significantly
      larger infarct volume, higher modified Rankin scale scores, and lower SD and
      coefficient of variation (CV) of -systolic BP in the hyperacute phase than shown
      by patients without insular infarction (p < 0.01, p < 0.01, p = 0.02, and p =
      0.03, respectively). The SD and CV of systolic BP in the hyperacute phase showed
      significant differences among the 3 groups with right insular infarction, with
      left insular infarction, and without insular infarction (p < 0.05 and p < 0.05,
      respectively). There was a tendency for the systolic BP variability to be lower
      in patients with right anterior insular infarction than in patients with infarcts
      in other areas. CONCLUSION: The right insular cortex, especially the anterior
      part, might be a hub for autonomic nervous regulation.

PMID- 29334681
TI  - Is There Any Common Pathophysiology between Central Nervous System Lupus and
      Parkinson's Disease?

PMID- 29334682
TI  - Body Mass Index and Plasma P-Selectin before Coronary Stenting Predict High
      Residual Platelet Reactivity at 6 Months on Dual Antiplatelet Therapy.
AB  - BACKGROUND: High residual platelet reactivity (HRPR) during dual antiplatelet
      therapy (DAPT) may impact clinical outcomes following percutaneous coronary
      interventions (PCI). However, whether any biomarkers assessed before PCI at DAPT
      loading may predict delayed maintenance HRPR is not clear. OBJECTIVE: The aim of
      this study was to determine whether conventional clinical or laboratory indices
      at loading before stenting may predict HRPR at 6 months of maintenance DAPT.
      METHODS: The study was designed on a single-center prospective cohort, and
      included 94 pre-PCI patients. All patients underwent elective PCI with drug
      eluting stent implantation, and received DAPT with aspirin and clopidogrel.
      Platelet reactivity was assessed with 5 MUmol/L of adenosine diphosphate-induced
      light transmission aggregometry before PCI, but after 24 h of DAPT loading, and
      repeated at 6 months. Baseline clinical characteristics, CYP2C19 polymorphism, C
      reactive protein, soluble P-selectin, CD40L, interleukin-6, PAI-1 levels, and von
      Willebrand factor activity were analyzed. RESULTS: The incidence (light
      transmission aggregometry <50%) of prestent HRPR was 16%. By univariate
      regression, body mass index (BMI; p = 0.02), total cholesterol (p = 0.01), low
      density lipoproteins (p = 0.004), CYP2C19*2 allele carriage (p = 0.006), soluble
      P-selectin (p = 0.009), and von Willebrand factor (p = 0.04) were linked to
      future HRPR. However, multivariate regression analysis suggested that only BMI
      and P-selectin were independent predictors of HRPR. CONCLUSIONS: Platelet
      reactivity before elective stenting is associated with numerous biomarkers;
      however, only BMI and soluble P-selectin were independent predictors of future
      HRPR during maintenance-phase DAPT. This may be important for future tailored
      antiplatelet strategies in patients with metabolic syndrome and diabetics.

PMID- 29334683
TI  - Epigenetic Silencing of the MLH1 Promoter in Relation to the Development of
      Gastric Cancer and its use as a Biomarker for Patients with Microsatellite
      Instability: a Systematic Analysis.
AB  - BACKGROUND/AIMS: Human mutL homolog 1 (MLH1) promoter methylation was reported in
      gastric cancer (GC). This study determined the clinicopathological, prognostic,
      and diagnostic effects of MLH1 promoter methylation in GC. METHODS: The combined
      odds ratio (OR) or hazard ratio (HR) and their corresponding 95% confidence
      intervals (95% CI) were calculated. The pooled sensitivity, specificity, and area
      under the curve (AUC) were analyzed. RESULTS: A total of 4654 GC patients and
      3669 non-malignant controls were identified in this systematic analysis. MLH1
      promoter methylation was significantly higher in GC samples than in gastric
      adenomas, chronic gastritis, adjacent tissues, normal gastric mucosa, and normal
      healthy blood samples, but it exhibited a similar frequency in GC vs. intestinal
      metaplasia and dysplasia samples. MLH1 promoter methylation correlated with age
      and microsatellite instability (MSI), but it was not associated with gender, H.
      pylori infection, smoking, drinking behaviors, pathological histology, tumor
      differentiation, clinical stage, lymph node status, distant metastasis, or
      overall survival of GC. MLH1 promoter methylation exhibited a poor sensitivity
      value (< 0.5) in patients with GC compared with adjacent tissues, gastric
      adenomas, chronic gastritis, normal gastric mucosa, and normal healthy blood
      samples. The pooled sensitivity, specificity, and AUC of MLH1 promoter
      methylation in GC with MSI vs. GC with microsatellite stability (MSS) samples
      were 0.64, 0.96, and 0.90, respectively. CONCLUSIONS: Our results suggest that
      the detection of MLH1 promoter methylation may be a potential prognostic
      biomarker for GC patients with MSI.

PMID- 29334684
TI  - Aberrant Connectivity in Mild Cognitive Impairment and Alzheimer Disease Revealed
      by Multimodal Neuroimaging Data.
AB  - BACKGROUND: Making use of multimodal data simultaneously to understand the neural
      mechanism of mild cognitive impairment (MCI) has been in the focus nowadays. The
      simultaneous use of multimodal data can take advantage of each modality which may
      only provide the view of one specific aspect of the brain. OBJECTIVE: To this
      end, the present study used structural magnetic resonance imaging (sMRI),
      fluorodeoxyglucose positron emission tomography (FDG-PET) and florbetapir PET to
      reveal the integrated brain network between MCI and normal controls (NCs).
      METHODS: In this study, 116 MCI, 116 NC and 116 Alzheimer disease (AD) subjects
      from the Alzheimer's Disease Neuroimaging Initiative were included for the
      evaluation of the brain covariance graphic model. Sparse inverse covariance
      estimation was utilized to get the graphic model. RESULTS: The connections among
      different brain regions were quite different between NC and MCI or between MCI
      and AD subjects (p < 0.01). The number of connections, which were represented by
      the covariance among different brain regions in the graphic model, decreased from
      NC to MCI and then AD, especially in the temporal lobe, occipital-parietal lobe
      and parietal-temporal lobe. CONCLUSION: These findings are good evidence to
      reveal the difference between MCI or AD and NC, and enhance the understanding of
      MCI.

PMID- 29334685
TI  - Observation of a phononic quadrupole topological insulator.
AB  - The modern theory of charge polarization in solids is based on a generalization
      of Berry's phase. The possibility of the quantization of this phase arising from
      parallel transport in momentum space is essential to our understanding of systems
      with topological band structures. Although based on the concept of charge
      polarization, this same theory can also be used to characterize the Bloch bands
      of neutral bosonic systems such as photonic or phononic crystals. The theory of
      this quantized polarization has recently been extended from the dipole moment to
      higher multipole moments. In particular, a two-dimensional quantized quadrupole
      insulator is predicted to have gapped yet topological one-dimensional edge modes,
      which stabilize zero-dimensional in-gap corner states. However, such a state of
      matter has not previously been observed experimentally. Here we report
      measurements of a phononic quadrupole topological insulator. We experimentally
      characterize the bulk, edge and corner physics of a mechanical metamaterial (a
      material with tailored mechanical properties) and find the predicted gapped edge
      and in-gap corner states. We corroborate our findings by comparing the mechanical
      properties of a topologically non-trivial system to samples in other phases that
      are predicted by the quadrupole theory. These topological corner states are an
      important stepping stone to the experimental realization of topologically
      protected wave guides in higher dimensions, and thereby open up a new path for
      the design of metamaterials.

PMID- 29334686
TI  - Fat Mass and Obesity-Related Gene Variants rs9939609 and rs7185735 are Associated
      with Second-Generation Antipsychotic-Induced Weight Gain.
AB  - INTRODUCTION: Weight gain is a limiting and frequent adverse effect of second
      generation antipsychotic therapy. Identifying genetic risk factors would
      significantly improve pharmacotherapy. METHODS: We focused on rs7185735 and
      rs9939609, 2 common single nucleotide polymorphisms of the fat mass and obesity
      associated (FTO) gene reported to be associated with obesity. Three-hundred fifty
      Caucasian inpatients were included in a naturalistic study. RESULTS: After 4
      weeks of treatment, we did not observe any significant association of
      polymorphisms with weight change in the whole study population (p>0.05). In a
      subpopulation without additional weight-inducing comedication (n=178), G-allele
      carriers of rs7185735 gained 3.4 times more weight (1.69 kg+/-3.1 kg, p=0.019)
      than AA genotypes (0.49 kg+/-3.1 kg). A-allele carriers of rs9939609 gained 3.1
      times more weight (1.65 kg+/-3.1 kg, p=0.029) than TT genotypes (0.54 kg+/-3.2
      kg). DISCUSSION: Our findings confirm the role of the FTO gene as a high
      potential risk factor for obesity and indicate a value for predicting a weight
      gain induced by second-generation antipsychotics. Further, we detected an
      additive effect of FTO rs7185735 and MC4R rs17782313.

PMID- 29334687
TI  - Cognitive Deficits in Methamphetamine Users: How Strong is The Evidence?
AB  - Methamphetamine use has spread in many European countries and the United States.
      The current review provides a summary and critical analysis of research on
      cognitive deficits associated with methamphetamine, also known as "crystal meth."
      The literature search performed for this review led us to the hypothesis that
      methamphetamine use is associated with persistent changes in brain metabolism
      that result in various impairments, such as deficits in memory, attention, and
      concentration. The dopaminergic system in particular seems to be affected. Some
      studies indicate that cognitive impairments may improve when users become
      abstinent, but results of other studies are conflicting. This review discusses
      these findings and the consequences for the development of a specific addiction
      treatment for methamphetamine.

PMID- 29334688
TI  - [Guideline for the Diagnosis and Treatment of Asthma - Guideline of the German
      Respiratory Society and the German Atemwegsliga in Cooperation with the
      Paediatric Respiratory Society and the Austrian Society of Pneumology].

PMID- 29334689
TI  - 'Stick with your own kind, or hang with the locals?' Implications of shoaling
      strategy for tropical reef fish on a range-expansion frontline.
AB  - Range shifts of tropical marine species to temperate latitudes are predicted to
      increase as a consequence of climate change. To date, the research focus on
      climate-mediated range shifts has been predominately dealt with the physiological
      capacity of tropical species to cope with the thermal challenges imposed by
      temperate latitudes. Behavioural traits of individuals in the novel temperate
      environment have not previously been investigated, however, they are also likely
      to play a key role in determining the establishment success of individual species
      at the range-expansion forefront. The aim of this study was to investigate the
      effect of shoaling strategy on the performance of juvenile tropical reef fishes
      that recruit annually to temperate waters off the south east coast of Australia.
      Specifically, we compared body-size distributions and the seasonal decline in
      abundance through time of juvenile tropical fishes that shoaled with native
      temperate species ('mixed' shoals) to those that shoaled only with conspecifics
      (as would be the case in their tropical range). We found that shoaling with
      temperate native species benefitted juvenile tropical reef fishes, with
      individuals in 'mixed' shoals attaining larger body-sizes over the season than
      those in 'tropical-only' shoals. This benefit in terms of population body-size
      distributions was accompanied by greater social cohesion of 'mixed' shoals across
      the season. Our results highlight the impact that sociality and behavioural
      plasticity are likely to play in determining the impact on native fish
      communities of climate-induced range expansion of coral reef fishes.

PMID- 29334690
TI  - Intestinal metabolism of Polygonum cuspidatum in vitro and in vivo.
AB  - Rhizoma et Radix Polygoni Cuspidati (RRPC) is commonly prescribed for the
      treatment of amenorrhea, arthralgia, jaundice and abscess in traditional Chinese
      medicine. Previous pharmacological studies have indicated that polyphenols are
      the main pharmacological active ingredients in RRPC. Meanwhile, the poor
      bioavailability of polyphenols in RRPC implies that those components are probably
      metabolized by intestinal bacteria before absorption. However, there is rather
      limited information about RRPC''s metabolites produced by intestinal bacteria and
      the intestinal absorbed constituents. In the present study, the metabolites were
      characterized after the aqueous extract of RRPC was incubated with the crude
      enzyme of human intestinal bacteria in vitro. The metabolic characteristics of
      glycosides in RRPC were figured out by comparing the metabolic profiles of emodin
      8-O-beta-d-glucopyranoside and polydatin between aqueous extract of RRPC and
      equivalent amounts of these two glycosides. The transitional constituents
      absorbed into blood were investigated in rats via intraduodental administration
      and portal vein intubation. A total of 38 prototype components and 43 metabolites
      were detected and characterized in vivo. The overall results demonstrated that
      the intestinal bacteria played an important role in the metabolism of RRPC, and
      the main metabolic pathways were hydrolysis in vitro, glucuronidation and
      sulfation in vivo.

PMID- 29334691
TI  - A meta-analysis of the effects of bariatric surgery on fracture risk.
AB  - Bariatric surgery effectively treats morbid obesity. However, the negative effect
      of this surgery on the bone is concerning. The aim of this meta-analysis was to
      investigate the fracture risk associated with bariatric surgery in morbidly obese
      subjects. Relevant studies published from database inception to September 2017
      were identified in PubMed, Embase and the Cochrane Library. The Newcastle-Ottawa
      Scale was used to evaluate the quality of the observational studies, and the
      Jadad score evaluated randomized controlled trials. Among the 1003 studies
      initially identified, five observational trials and one randomized controlled
      trial were eligible for inclusion. All studies included in the meta-analysis were
      considered high quality. Risk for any type of fracture was higher in the surgical
      group than in the non-surgical group (risk ratio [RR] 1.29, 95% confidence
      interval [CI] 1.18-1.42). After surgery, the fracture risk in non-vertebral sites
      was significantly increased, especially in the upper limbs (RR 1.42, 95% CI 1.08
      1.87; and RR 1.68, 95% CI 1.15-2.45). Compared with those with restrictive
      procedures, subjects who underwent mixed restrictive and malabsorptive procedures
      tended to have an increased fracture risk (RR 1.54, 95% CI 0.96-2.46). To
      conclude, bariatric surgery is associated with an increased risk of total and non
      vertebral fractures, especially in the upper limbs.

PMID- 29334692
TI  - Body mass index, abdominal adiposity, weight gain and risk of developing
      hypertension: a systematic review and dose-response meta-analysis of more than
      2.3 million participants.
AB  - OBJECTIVE: This study aimed to test the association between anthropometric
      measures and risk of developing hypertension. METHODS: We did a systematic search
      using PubMed and Scopus, from inception up to January 2017. Prospective cohort
      studies reporting the risk estimates of hypertension for three or more
      quantitative categories of indices of general and abdominal adiposity were
      included. Summary relative risks were calculated using random-effects models.
      RESULTS: Fifty-seven prospective cohort studies were included. Summary relative
      risks were 1.49 (95% confidence interval [CI]: 1.41, 1.58; I2  = 97.4%, n = 50)
      for a five-unit increment in body mass index, 1.27 (95%CI: 1.15, 1.39; I2  =
      95.0%, n = 14) for a 10-cm increment in waist circumference, 1.16 (95%CI: 1.09,
      1.23; I2  = 77.8%, n = 5) for weight gain equal to a one-unit increment in BMI,
      and 1.37 (95%CI: 1.24, 1.51; I2  = 76.4%, n = 8) and 1.74 (95%CI: 1.35, 2.13; I2 
      = 58.9%, n = 4) for a 0.1-unit increment in waist-to-hip ratio and waist-to
      height ratio, respectively. The risk of hypertension increased continuously with
      increasing all anthropometric measures, and also along with weight gain.
      CONCLUSION: Being as lean as possible within the normal body mass index range may
      be the best suggestion in relation to primary prevention of hypertension.

PMID- 29334693
TI  - The frequency of family meals and nutritional health in children: a meta
      analysis.
AB  - Findings on the relationship between family meal frequency and children's
      nutritional health are inconsistent. The reasons for these mixed results have to
      date remained largely unexplored. This systematic review and meta-analysis of 57
      studies (203,706 participants) examines (i) the relationship between family meal
      frequency and various nutritional health outcomes and (ii) two potential
      explanations for the inconsistent findings: sociodemographic characteristics and
      mealtime characteristics. Separate meta-analyses revealed significant
      associations between higher family meal frequency and better overall diet quality
      (r = 0.13), more healthy diet (r = 0.10), less unhealthy diet (r = -0.04) and
      lower body mass index, BMI (r = -0.05). Child's age, country, number of family
      members present at meals and meal type (i.e. breakfast, lunch or dinner) did not
      moderate the relationship of meal frequency with healthy diet, unhealthy diet or
      BMI. Socioeconomic status only moderated the relationship with BMI. The findings
      show a significant relationship between frequent family meals and better
      nutritional health - in younger and older children, across countries and
      socioeconomic groups, and for meals taken with the whole family vs. one parent.
      Building on these findings, research can now target the causal direction of the
      relationship between family meal frequency and nutritional health.

PMID- 29334694
TI  - Home alone: a systematic review and meta-analysis on the effects of individual
      housing on body weight, food intake and visceral fat mass in rodents.
AB  - Rats and mice are widely used to study environmental effects on psychological and
      metabolic health. Study designs differ widely and are often characterized by
      varying (social) housing conditions. In itself, housing has a profound influence
      on physiology and behaviour of rodents, affecting energy balance and sustainable
      metabolic health. However, evidence for potential long-term consequences of
      individual versus social housing on body weight and metabolic phenotype is
      inconsistent. We conducted a systematic literature review and meta-analyses
      assessing effects of individual versus social housing of rats and mice, living
      under well-accepted laboratory conditions, on measures of metabolic health,
      including body weight, food intake and visceral adipose tissue mass. Seventy-one
      studies were included in this review; 59 were included in the meta-analysis.
      Whilst housing did not affect body weight, both food intake and visceral adipose
      tissue mass were significantly higher in individually compared with socially
      housed animals. A combination of emotional stress and lack of social
      thermoregulation likely contributed to these effects. Increased awareness of
      consequences and improved specifications of housing conditions are necessary to
      accurately evaluate efficacy of drugs, diets or other interventions on metabolic
      and other health outcomes because housing conditions are rarely considered as
      possible moderators of reported outcomes.

PMID- 29334695
TI  - Complex interplay among adiposity, insulin resistance and bone health.
AB  - Obesity and osteoporosis are common public health problems. Paradoxically, while
      obesity is associated with higher bone density, type 2 diabetic obese individuals
      have an increased fracture risk. Although obesity and insulin resistance co
      exist, some obese individuals remain insulin-sensitive. We suggest that the
      apparent paradox relating obesity, bone density and fracture risk in type 2
      diabetes may be at least partly influenced by differences in bone strength and
      quality between insulin-resistant and insulin-sensitive obese individuals. In
      this review, we focus on the complex interplay between, adiposity, insulin
      resistance and osteoporotic fracture risk and suggest that this is an important
      area of study that has implications for individually tailored and targeted
      treatment to prevent osteoporotic fracture in obese type 2 diabetic individuals.

PMID- 29334696
TI  - Mast cells participate in chronic low-grade inflammation within adipose tissue.
AB  - Obesity is reckoned as one of the civilization diseases, posing a considerable
      global health issue. Evidence points towards a contribution of multitude immune
      cell populations in obesity pathomechanism and the development of chronic low
      grade inflammation in the expanded adipose tissue. Notably, adipose tissue is a
      reservoir of mast cells which number in individuals with obesity particularly
      increased. Some of them tend to degranulation what generate secretion of strong
      pro-inflammatory and regulatory mediators, as well as cytokines/chemokines.
      Several lines of evidence suggest that mast cells are strictly associated with
      pro-inflammatory status in adipose tissue by their indirect impact on immune cell
      attraction and activation. Furthermore, mast cells affect adipose tissue
      remodelling and fibrosis by adipocyte differentiation, fibroblast proliferation
      and enhancing extracellular matrix proteins expression. This review will
      summarize current knowledge on mast cell features and their role in the
      development of chronic low-grade inflammation within adipose tissue.

PMID- 29334697
TI  - Sepsis-induced activation of endogenous GLP-1 system is enhanced in type 2
      diabetes.
AB  - BACKGROUND: High levels of circulating GLP-1 are associated with severity of
      sepsis in critically ill nondiabetic patients. Whether patients with type 2
      diabetes (T2D) display different activation of the endogenous GLP-1 system during
      sepsis and whether it is affected by diabetes-related metabolic parameters are
      not known. METHODS: Serum levels of GLP-1 (total and active forms) and its
      inhibitor enzyme sDPP-4 were determined by ELISA on admission and after 2 to 4
      days in 37 sepsis patients with (n = 13) and without T2D (n = 24) and compared to
      normal healthy controls (n = 25). Correlations between GLP-1 system activation
      and clinical, inflammatory, and diabetes-related metabolic parameters were
      performed. RESULTS: A 5-fold (P < .001) and 2-fold (P < .05) increase in active
      and total GLP-1 levels, respectively, were found on admission as compared to
      controls. At 2 to 4 days from admission, the level of active GLP-1 forms in
      surviving patients were decreased significantly (P < .005), and positively
      correlated with inflammatory marker CRP (r = 0.33, P = .05). T2D survivors
      displayed a similar but more enhanced pattern of GLP-1 response than nondiabetic
      survivors. Nonsurvivors demonstrate an early extreme increase of both total and
      active GLP-1 forms, 9.5-fold and 5-fold, respectively (P < .05). The initial and
      late levels of circulating GLP-1 inhibitory enzyme sDPP-4 were twice lower in all
      studied groups (P < .001), compared with healthy controls. CONCLUSIONS: Taken
      together, these data indicate that endogenous GLP-1 system is activated during
      sepsis. Patients with T2D display an enhanced and prolonged activation as
      compared to nondiabetic patients. Extreme early increased GLP-1 levels during
      sepsis indicate poor prognosis.

PMID- 29334698
TI  - Endoscopic ultrasound and the liver: current applications and beyond.
AB  - The diagnosis and management of many gastrointestinal conditions has been
      augmented by the development of endoscopic ultrasound. Its role in the diagnosis
      and management of liver disease has been somewhat limited, but with the rapid
      development of therapeutic advancements it has quickly emerged as a useful tool
      in the management of complex hepatic conditions. This includes its use in the
      management of complications of portal hypertension as well as its use in liver
      lesions and cancer. In this paper, we review case studies, case series and trials
      for hepatic applications of endoscopic ultrasound to provide an overview of its
      utilization in this field and demonstrating its more novel applications for
      future use.

PMID- 29334699
TI  - Tokyo Guidelines 2018: updated Tokyo Guidelines for the management of acute
      cholangitis/acute cholecystitis.

PMID- 29334700
TI  - [Hygiene and health: current situation and prospective].

PMID- 29334701
TI  - [Pay attention to the nutrition and health of pregnancy women with advanced age].

PMID- 29334702
TI  - [Prevalence of calf muscle cramps and influencing factors for pregnant women in
      China during 2010-2012].
AB  - Objective: To investigate the prevalence of calf muscle cramps and possible
      influencing factors for pregnant women in China. Methods: Using a multi-stage
      stratified probability proportional to size cluster randomization sampling method
      during 2010-2012. A total of 3 582 pregnant women were investigated at 150
      counties from 31 provinces in China mainland. Information on calf muscle cramps,
      demographic socio-economic status, pregnancy information, and the physical
      activities was collected through questionnaires. The semi-quantitative food
      frequency questionnaire (FFQ) was used to collect food intake of pregnant women.
      Dynamic cluster analysis was used to assess dietary pattern. Multiple logistic
      regression was used to investigate the possible influencing factors for calf
      muscle cramps. Results: The prevalence of calf muscle cramps was 32.9% (1 180/3
      582) in Chinese pregnant women, which was 11.6% (87/748), 28.2% (420/1 492), and
      50.2% (673/1 342), respectively, during the first, second and third trimester.
      There were significant differences between them (chi(2)=349.16, P<0.001). Dietary
      patterns of the pregnant women were classified into three groups, which called
      relatively balanced pattern, high vegetables and fruits pattern, and high dairy
      pattern. Among the three groups, the prevalence of calf muscle cramps was 32.0%
      (952/2 971), 37.2% (186/500), and 37.8% (42/111), with significant differences
      (chi(2)=6.39, P=0.041). The OR (95%CI) values of calf muscle cramps in the second
      and third trimester was 2.96 (2.28-3.83), and 8.02 (6.16-10.44), respectively,
      comparing with the first trimester. The OR (95%CI) values of calf muscle cramps
      in the women taking calcium before pregnant was 1.45 (1.19-1.76), comparing with
      the one who was not taken. The OR (95%CI) values of calf muscle cramps in the
      women who had been diagnosed by pregnancy-induced hypertension was 5.76 (2.06
      16.12), comparing with the one who had not been diagnosed. The OR (95%CI) values
      of calf muscle cramps in the high vegetables and fruits pattern and high dairy
      pattern was 1.13 (0.91-1.41), and 1.18 (0.76-1.81), respectively, comparing with
      the relatively balanced pattern. Conclusion: The prevalence of calf muscle cramps
      was relatively high in Chinese pregnant women, which was significantly different
      among three trimesters. The residential areas, occupation, and pregnancy-induced
      hypertension might be related to the prevalence of calf muscle cramps. However,
      there was no significant difference among different dietary patterns.

PMID- 29334703
TI  - [The influencing factors of anemia for pregnant women between 2010-2012 in
      China].
AB  - Objective: To investigate the prevalence of anemia and related risk factors for
      pregnant women in China. Method: Based on Chinese National Nutrition and Health
      Surveillance 2010-2012, a total of 3 501 pregnant women were investigated from
      150 counties of 31 provinces, municipalities and autonomous regions in China,
      using a multi-stage stratified cluster randomization sampling method. General
      information of pregnant women, health status, and food intake during the
      gestation, was collected through a questionnaire investigation. 6 ml fasting
      venous blood was collected for the determination of hemoglobin concentration.
      Data were analyzed using multiple logistic regression to investigate the
      prevalence of anemia and the related influencing factors. Results: The 605 of 3
      501 pregnant women had anemia. The prevalence of anemia was 17.2%; and mild
      anemia accounted for about 61.0% (369/605). Compared with the pregnant women
      living in the large cities, the OR (95%CI) of those living in the poor rural
      areas was 1.46 (1.08-1.98). Compared with the pregnant women living in the south
      area of China, the OR (95%CI) of those living in the north area of China was 1.39
      (1.15-1.68); Compared with the pregnant women in the first trimester, the OR
      (95%CI) of those in the second trimester and the third trimester were 1.79 (1.33
      2.43) and 2.11 (1.56-2.85), respectively. The OR (95%CI) of pregnant women who
      had used folic acid supplementation within the 6 months prior to gestation was
      0.76 (0.63-0.93) compared with those who had not used. Conclusion: From 2010 to
      2012, the epidemic characteristics of anemia was mild for the pregnant women in
      China, and pregnant women residential areas, periods of pregnancy and whether to
      take folic acid were related to anemia.

PMID- 29334704
TI  - [Status and related factors for gestational weight gain of Chinese pregnant women
      during 2010-2012].
AB  - Objective: To examine the status and related factors for gestational weight gain
      of Chinese pregnant women at different trimesters in 2010-2012. Methods:
      Participants were from Chinese National Nutrition and Health Surveillance in 2010
      2012. Using a multi-stage stratified cluster random sampling method, we recruited
      2 805 singleton pregnant women with gestational age 13 weeks or more from 31
      provinces of China. A standard questionnaire was used to collect general
      information and pre-pregnancy weight; body weight and height of pregnant women
      were measured using a unified weighing scale and stadiometer, dietary intake
      during the previous year was collected using a food frequency questionnaire. A
      multiple logistic regression was used to analyze potential factors associated
      with appropriate gestational weight gain. Results: Among 2 805 pregnant women, 1
      441 were in the second (13-27 weeks) and 1 364 in the third trimesters (>=28
      weeks) . In the 2(nd) trimester, 229 cases (15.9%), 440 cases (30.5%) and 772
      cases (53.6%) were insufficient gestational weight gain, appropriate gestational
      weight gain and excessive gestational weight gain respectively. So were 256 cases
      (18.8%), 474 cases (34.8%), 634 cases (46.5%) in the 3(rd) trimester
      respectively. In the multivariate unconditional logistic model, less fruit intake
      was associated with insufficient weight gain for women in the 2(nd) trimester (OR
      (95%CI): 1.58 (1.06-2.34)). Pregnant women with Han ethnicity who live in the
      small/medium city had lower risk of insufficient weight gain in the 3(rd)
      trimester (OR (95%CI): 0.58 (0.34-0.98)). Those pregnant women with physical
      activity <1 hour/day had a higher risk of excessive weight gain (OR (95%CI): 1.33
      (1.02-1.73)). Conclusion: The prevalence of appropriate gestational weight gain
      was low in China. Our study suggests that pregnant weight gain is associated with
      fruit intake, types of residential area and physical activity.

PMID- 29334705
TI  - [Gestational weight gain and optimal ranges in Chinese mothers giving singleton
      and full-term births in 2013].
AB  - Objective: To analyze the status of gestational weight gain (GWG) among Chinese
      mothers who gave singleton and full-term births, and to look at optimal GWG
      ranges. Methods: In 2013, using the multi-stage stratified and population
      proportional cluster sampling method, we investigated 8 323 mother-child pairs at
      their 0-24 months postpartum from 55 counties (cities/districts) of 30 provinces
      (except Tibet) in mainland China. Questionnaire was used to collect data on body
      weight before pregnancy and delivery, diseases during gestation, hemorrhage or
      not at postpartum, child birth weight and length, and other information about
      pregnant outcomes. We measured mother's body weight and height, and child's body
      weight and length. Based on 'Chinese Adult Body Weight Standard', we divided
      mothers into four groups according to their body weight before pregnancy: low
      weight (BMI<18.5 kg/m(2)), normal weight (BMI 18.5-23.9 kg/m(2)), overweight (BMI
      24.0-27.9 kg/m(2)) and obesity (BMI>=28.0 kg/m(2)). The status of GWG was
      assessed by IOM optimal GWG guidelines. Chinese optimal GWG ranges were
      calculated according to the association of GWG with pregnant outcomes and
      anthropometry of mothers and children, and according to P25-P75 of GWG among
      mothers who had good pregnant outcomes and good anthropometry, and whose children
      had good anthropometry. The status of GWG was assessed by the new optimal ranges.
      Results: P50 (P25-P75) of GWG among the 8 323 mothers was 15.0 (10.0-19.0) kg.
      According to the proposed optimal GWG ranges of IOM, the proportions of
      inadequate, optimal and excessive GWG accounted for 27.2% (2 263 mothers), 36.2%
      (3 016 mothers) and 36.6% (3 044 mothers). The optimal GWG ranges for low weight,
      normal weight, overweight and obesity were 11.5-18.0, 10.0-15.0, 8.0-14.0 and 5.0
      11.5 kg. Based on these optimal GWG ranges established in this study, the rates
      of inadequate, optimal and excessive GWG were 15.7% (1 303 mothers), 45.0% (3 744
      mothers) and 39.3% (3 276 mothers), and these rates were significantly different
      from that defined by the IOM standards (chi2=345.36, P<0.001). Conclusion: The
      median of GWG among Chinese mothers is 15.0 kg, which is at a relatively higher
      level. This study suggests the optimal GWG ranges for Chinese women who give
      singleton and full-term babies, which appears lower than IOM's.

PMID- 29334706
TI  - [Analysis of mothers' acceptance of HPV vaccination of adolescent girls in
      Xiamen].
AB  - Objective: To survey the mothers' acceptance of the HPV vaccination for their
      adolescent girls in Xiamen and to explore the influencing factors. Methods:
      Mothers of adolescent girls were selected by multistage cluster random sampling.
      Data of demography of the mothers and girls, the knowledge and attitude of
      cervical cancer and HPV vaccine of the mothers were collected. The influencing
      factors of mothers' attitudes were analyzed with univariate and multivariate
      logistic regression. Results: A total of 2 307 mothers were selected. The average
      age of mothers was (38.0+/-4.7) years. 13.1% (300) of the mothers had a family
      history of malignant tumor. The mothers' acceptance for vaccinating girls was
      61.9% (1 428). The awareness rates of HPV and HPV vaccine were 42.5% (980) and
      21.4% (493), respectively. Mothers who had family history of cancer (OR=1.36,
      95%CI:1.02-1.82) showed a greater willingness to vaccinate their girls than the
      mothers who had not. Mothers who had knowledge of HPV (OR=1.32, 95%CI:1.08-1.62)
      and HPV (OR=2.03, 95%CI:1.56-2.66) vaccines showed a greater willingness to
      vaccinate their girls than the mothers who had not. Conclusion: The mothers'
      acceptance to vaccinate adolescent girls against cervical cancer needs to be
      raised, especially for the mothers who had not family history of cancer, no
      knowledge of HPV and HPV vaccines.

PMID- 29334708
TI  - [Analysis of measles immunity level and serological susceptibility among Yunnan
      residents aged >=20 years].
AB  - Objective: To evaluate the population immunity to measles and explore the factors
      associated with measles susceptibility in Yunnan residents aged >=20 years.
      Methods: 2 689 residents aged >=20 years were selected by multistage stratified
      systematic randomized sampling in 252 villages of 42 counties in Yunnan Province
      between June and September in 2015. Each subject was surveyed by the same
      questionnaire, including general information, measles contained vaccine history,
      measles history, and 5 ml blood sample of each subject was collected. Serum IgG
      antibodies against measles virus were measured by ELISA. Positive was defined as
      the antibody concentration >=250 mU/ml, and negative as <250 mU/ml. Non
      conditional logistic regression model was used analyze the factors associated
      with measles susceptibility in adults. Results: Among 2 689 subjects, 1 214 were
      males (45.15%), and the overall positive rate of measles IgG antibody was 89.77%.
      Compared with subjects from the region where economic development was low,
      subjects from the region where economic development was moderate were likely to
      be susceptible to measles virus (OR=1.81, 95%CI: 1.33-2.47). Four age groups had
      higher risk of being susceptible to measles virus (compared with >=40 years: 20
      24 years old, OR=2.04, 95%CI: 1.26-3.31; 25-29 years old, OR=3.72, 95%CI: 2.37
      5.86; 30-34 years old, OR=1.94, 95%CI: 1.22-3.09; 35-39 years old, OR=1.81,
      95%CI: 1.07-3.05). Conclusion: Our results suggest that the serological
      susceptibility in adults (20-39 years), especially adults from the regions where
      the economic development was moderate, should be concerned. The additional
      vaccination strategy targeting young adults is important for reducing the risk of
      measles infection.

PMID- 29334707
TI  - [Comparing the immunogenicity and safety of sequential inoculation of sIPV
      followed by bOPV (I+III) in different dosage forms].
AB  - Objective: To compare the safety and immunogenicity of two different sequential
      schedules of inactivated poliomyelitis vaccine made from Sabin strain (sIPV)
      followed by typeI+III bivalent oral poliovirus vaccine (bOPV) in Drug Candy (DC)
      form or liquid dosage form). Methods: This randomized, blinded, single center,
      parallel-group controlled trial was done from September 2015 to June 2016 in
      Liuzhou, Guangxi province. Healthy infants aged >=2 months were eligible for
      enrollment and divided into 1sIPV+2bOPV or 2sIPV+1bOPV sequential schedules.
      According to the bOPV dosage form each sequential schedules, the subjects again
      were divided into drug candy(DC) form or liquid dosage form group, being
      1sIPV+bOPV (DC)/1sIPV+2bOPV(liquid)/2sIPV+1bOPV(DC)/2sIPV+1bOPV(liquid).
      According to 0, 28, 56 d immunization schedule, Each group were given 3 doses. We
      recorded adverse events during the clinical trial (399 participants who receive
      at least one dose). 28 days post-Dose 3, we receive a total of 350 blood samples
      (excluding the quitters or subjects against trial plan), using cell culture trace
      against polio virus neutralization test I, II, III neutralizing antibody (GMT),
      calculating the antibody positive rate.PolioI,IIand III antibody titers were
      assessed by virus-neutralizing antibody assay and the seroconversion (4-fold
      increase in titer) from pre-Dose 1 to 28 days post-Dose 3 was calculated (total
      350 samples) . Results: During the vaccination, the incidence of AEs in
      1sIPV+2bOPV(DC), 1sIPV+2bOPV (liquid), 2sIPV+1bOPV(DC), 2sIPV+1bOPV (liquid)
      group were 79%, 76%, 80% and 74% (chi(2)=1.23, P=0.747) , respectively. The
      severe AEs in groups were 6%, 5%, 6% and 4% (chi(2)=0.57, P=0.903) ,
      respectively, and none was considered to be vaccination related. 28 days after
      3(rd) vaccination, the seroconversion rates in 1sIPV+2bOPV (DC), 1sIPV+2bOPV
      (liquid), 2sIPV+1bOPV (DC), 2sIPV+1bOPV (liquid) group, were 99%, 100%, 99% and
      99% (chi(2)=0.94, P=0.815) , respectively, for type I poliovirus; and 47%, 57%,
      80%, 79% (chi(2)=31.56, P<0.001) , respectively, for type II; and were 100%, 99%,
      100%, 99% (chi(2)=2.02, P=0.568) , respectively, for type III. In each group, the
      GMT of antibody against poliovirus typeI were 4 539.68, 6 243.43, 6 819.53 and 7
      916.29 (F=25.87, P<0.001) , respectively; Type II were 12.98, 10.54, 63.75 and
      84.21 (F=8.68, P=0.034) , respectively; Type III were 1 172.55, 1 416.03, 2
      648.89 and 3 250.75 (F=14.50, P=0.002) , respectively. Conclusion: On the same
      sequential schedules, there was no significant difference between the dosage
      forms, all of them showed good safety and immunogenicity. In the same dosage
      forms with different sequential schedules, the seroconversion rate was higher in
      2 dose sIPV group than the 1 dose sIPV group, especially at the neutralizing
      antibody GMT level against polio type II and III after vaccination.

PMID- 29334709
TI  - [Molecular epidemiological study of human coronavirus OC43 in Shanghai from 2009
      2016].
AB  - Objective: To understand the epidemiological characteristics of Human coronavirus
      (HCoV), the patterns of emergence and circulation, and the genotype distribution
      of human coronavirus OC43 (HCoV-OC43) from November, 2009 to April, 2016 in
      Shanghai. Methods: A total of 6 059 respiratory specimens, including pharyngeal
      swab, sputum, nasopharyngeal aspirates and alveolar lavage fluid, as well as
      relative clinical data were collected from patients with acute respiratory
      infections from seven sentinel hospitals during November, 2009 to April, 2016 in
      Shanghai. Respiratory specimens were tested by RT-PCR with HCoV-conserved primers
      and subsequently genotyped by DNA sequencing. Using specific primers to amplify
      and sequence full-length Spike (S), RNA-dependent RNA polymerase (RDRP) and
      nucleocapsid (N) gene from HCoV-OC43 positive samples. Further genotype and
      phylogenetic analysis of HCoV-OC43 were performed by conducting phylogenetic
      trees. Results: Among 6 059 patients, the total frequency of HCoV was 63 (1.04%),
      in which HCoV-OC43 was the most frequently detected species with 34 positive
      samples, followed by human coronavirus 229E (HCoV-229E) and human coronavirus
      HKU1 (HCoV-HKU1) with 18 and 10 positive sample respectively. However, other HCoV
      like human coronavirus NL63 (HCoV-NL63), severe acute respiratory syndrome
      coronavirus (SARS-CoV) and Middle-East Respiratory Syndrome Coronavirus (MERS
      CoV), were not been detected, which illustrated that HCoV-OC43 was the dominant
      subtype. The full-length of S, RDRP and N gene were obtained from 29 HCoV-OC43
      positive samples. According to the sequence-analysis, 27 of which was genotype D,
      2 of which was genotype B and others genotype, including genotype E, F and G,
      were not detected. The result indicated that the genotype D may be the dominant
      genotype. Further analysis of S protein that help HCoV-OC43 to entry host cell
      and stimulate the host immune system to produce neutralizing antibody found that
      two important functional domains in S protein, N-terminal domain (NTD) and
      receptor-binding domain (RBD) contained more amino acid substitution and positive
      selection sites, accompanied with amino acid insertion/deletion. 13 positive
      selection sites were all located in the NTD or RBD, 10 of which were located in
      the NTD and 3 in the RBD. Conclusion: Human coronavirus OC43 was the major
      circulation human coronaviurs in Shanghai from 2009 to 2016, in which genotype D
      was the dominant genotype. NTD and RBD regions of the S protein were
      hypervariable region during HCoV-OC43 evolution, and had amino acid substitutions
      as well as amino acid insertion/deletion.

PMID- 29334710
TI  - [A study on genotype of 271 mycobacterium tuberculosis isolates in 6 prefectures
      in Yunnan Province].
AB  - Objective: To understand the characteristics of genotypes of Mycobacterium
      tuberculosis isolates in Yunnan province, and provide the molecular
      epidemiological evidence for prevention and control of tuberculosis in Yunnan
      Province. Methods: Mycobacterium Tuberculosis isolates were collected from 6
      prefectures of Yunnan province in 2014 and their Genetypes of Mycobacterium
      tuberculosis isolates were obtained using spoligotyping and multiple locus
      variable numbers of tandem repeats analysis (MLVA). The results of spoligotyping
      were entered into the SITVITWEB database to obtain the Spoligotyping
      International Type (SIT) patterns and the sublineages of MTB isolates. The
      genoyping patterns were clustered with BioNumerics (version 5.0). Results: A
      total of 271 MTB isolates represented patients were collected from six
      prefectures in Yunnan province. Out of these patients, 196 (72.3%) were male. The
      mean age of the patients was (41.9+/-15.1) years. The most MTB isolates were from
      Puer, totally 94 iusolates(34.69%). Spoligotyping analysis revealed that 151
      (55.72%) MTB isolates belonged to the Beijing genotype, while the other 120
      (44.28%) were from non-Beijing genotype; 40 genotypes were consisted of 24 unique
      genotypes and 16 clusters. The 271 isolates were differentiated into 30 clusters
      (2 to 17 isolates per cluster) and 177 unique genotypes, showing a clustering
      rate of 23.62%. Beijing genotype strains showed higher clustering rate than non
      Beijing genotype strains (29.14% vs 16.67%). The HGI of 12-locus VNTR in total
      MTB strains, Beijing genotype strains and non-Beijing genotype was 0.993, 0.982
      and 0.995 respectively. Conclusion: The Beijing genotype was the predominant
      genotype in Yunnan Province, the characteristics of Mycobacterium tuberculosis
      showed high genetic diversity. The genotyping data reflect the potential recent
      ongoing transmission in some area, which highlights the urgent need for early
      diagnosis and treatment of the infectious TB cases, to cut off the transmission
      and avoid a large TB outbreak.

PMID- 29334711
TI  - [Serologic surveillance indicators analysis among syphilis-infected pregnant
      women in East China].
AB  - Objective: To analyze serologic surveillance indicators during pregnancy among
      syphilis-infected women who delivered in 2013 in East China. Methods: Data were
      from national 'Information System of Prevention of Mother-to-child Transmission
      of HIV, syphilis and HBV Management' and in total 5 206 syphilis-infected
      pregnant women who delivered in 2013 and in East China were involved in the
      analysis. Information on demographic characters, laboratory tests, and treatment
      regimens were collected. The maternal non-treponemal testing surveillance and
      titer distribution were described and compare the proportions between pregnant
      women receiving standard testing and non-standard testing, taking baseline
      testing and testing before delivery or at the third trimester. Multivariate
      logistic regression model was analyzed using maternal titer control as dependent
      variable, using prior history of syphilis infection, syphilis stages, titer,
      gestational weeks of treatment initiation and treatment regimens as independent
      variables in 3 940 pregnant women with both baseline testing results and testing
      results before delivery or at the third trimester. Results: The ages of the 5 206
      syphilis infected pregnant women were (28.1+/-5.8) years old. The numbers of
      women received penicillin treatment, other treatment regimens and no treatment
      were 2 967 (57.0%), 281 (5.4%), and 1 958 (37.6%), respectively. The number of
      women with maternal seroconversion, 4-fold or greater titer decline, or titer
      increase were 349 (6.7%), 251 (4.8%) and 28 (0.5%). Multivariate analysis results
      showed that compared with pregnant women with prior history of syphilis, the
      OR(95%CI) for maternal titer control was 1.49 (1.18-1.88) among those with
      syphilis-infection history. Compared with pregnant women initiated treatment at
      28 gestational weeks or before, the OR (95%CI) for maternal titer control was
      4.09 (3.19-5.24) among those who initiated treatment after 28 gestational weeks.
      Compared with pregnant women initiated treatment at 28 gestational weeks or
      before, the OR (95%CI) for maternal titer control was 4.09 (3.19-5.24) among
      those who initiated treatment after 28 gestational weeks or received no
      treatment. Compared with pregnant women received penicillin treatment, the OR
      (95%CI) for maternal titer control among those received non-penicillin treatment
      and those received no treatment were 2.35 (1.46-3.76) and 1.55 (1.13-2.12),
      respectively. Conclusion: In East China, the proportion of women achieved
      seroconversion or 4-fold or greater titer decline during pregnancy was very low.
      Pregnant women with no prior history of syphilis infection, early maternal
      initiation of treatment, and penicillin treatment were more likely to reach
      maternal titer control.

PMID- 29334712
TI  - [The effect of ambient PM(10) on sperm quality in Wuhan].
AB  - Objective: To investigate the effect of exposure to particulate matter <=10 MUm
      in aerodynamic diameter (PM(10)) on sperm quality in different stages of sperm
      development. Methods: This cross-sectional study included 1 827 patients
      attending the reproductive medicine center in Renmin Hospital of Wuhan University
      during April 2013 to January 2015. Air pollution data from January 2013 to
      January 2015 was obtained from the database of Wuhan Municipal Environmental
      Protection Bureau. The generalized linear model was employed to assess the
      association between each exposure variables and sperm parameters for several
      exposure windows (0-9, 10-14, 15-69, 70-90, 0-90 days before sampling) . Results:
      The average levels of PM(10) was (116.2+/-71.6) MUg/m(3) during the research
      period. Sperm volume was (75.4+/-49.1) *10(6)/ml in sample population, (29.4+/
      16.2) % in progressive motility and (51.8+/-21.6) % in total motility. Exposure
      to PM(10) was inversely associated with sperm concentration (beta:-0.319; 95%CI:
      0.529,-0.046) during 70-90 lag days. PM(10) exposure during the 0-90 lag days was
      significantly associated with progressive motility (beta:-0.312; 95%CI:-0.527,
      0.097) and total motility (beta:-0.347; 95%CI:-0.636,-0.059) after adjusted for
      age, education level, BMI, smoking, abstinence time, temperature, humidity and
      season. Conclusion: Exposure to PM(10) was associated with statistically
      significant decrements in sperm concentration and motility, and the adverse
      impact on sperm concentration was significantly in early phases of
      spermatogenesis.

PMID- 29334713
TI  - [Prevalence and influential factors of stroke in Jiangxi Province in 2014].
AB  - Objective: To discuss the prevalence and influential factors of stroke among
      population in Jiangxi Province. Methods: Four cities in urban areas and four
      counties in rural areas were selected firstly, in which two districts or
      townships were selected; and then three communities or villages were chosen from
      each district and township, respectively, using the simple random sampling (SRS)
      method. Finally 15 269 subjects aging 15 years old or above, living in Jiangxi
      Province >=6 months were randomly selected to participate in this survey from
      November 2013 to August 2014. Information of population characteristics, life
      behavior way, individual disease history were collected through questionnaire
      survey, and height, weight, waist circumference, blood pressure, body fat rate,
      visceral fat index and so on were measured by instruments. Risk factors of stroke
      prevalence were analyzed by the unconditioned logistic regression analysis.
      Results: A total of 15 269 participants (6 267 males) from 15 364 eligible
      participants were included in the statistical analysis. Out of which, 7 793
      participants came from urban areas, and their average age was (53.04+/-17.91)
      years old. In this study, 226 stroke patients (117 males) were found among15 269
      participants, including 122 urban participants and 104 rural participants, whose
      average age was (67.76+/-9.74) years old. The prevalence of stroke was 1
      480.12/100 000 in 2014, which was separately 1 866.92/100 000 and 1 210.84/100
      000 among males and females. The prevalence of people aging (45-49) years old was
      413.79/100 000 (6/1 450) , while which among people aging 75 years old and above
      was 3 311.62/100 000 (61/1 842) . The prevalence of stroke among residents in
      Jiangxi presented an uprising tendency with age increasing (linear-by-linear
      association chi(2)=62.23, P<0.01). The research showed that when other
      influencing factors including gender, BMI, waist circumference, pulse-pressure
      difference, VAI, and sleeping time in non-working days were controlled,
      hypertensive patients had a higher risk of stroke than people without
      hypertension (OR=6.88, 95%CI: 4.90-9.67), drinkers had a higher risk of stroke
      than non-drinkers (OR=1.56, 95%CI: 1.17-2.08), compared with people <65 years
      old, people aged 65-74 years old and >=75 years old had a higher risk of stroke,
      the value of OR (95%CI) were 1.88 (1.36-2.59) and 1.97 (1.39-2.80), respectively,
      compared with people with normal body fat percentage, people whose body fat
      percentage on high side and people who with high body fat percentage had a higher
      risk of stroke, the value of OR (95%CI) were 1.71 (1.18-2.48) and 1.74 (1.18
      2.56), respectively, people with sleep time >8 h had a higher risk of stroke than
      those with sleep time of 6-8 h. Conclusion: There was a high stroke prevalence
      among residents in Jiangxi province. Hypertension, drinking, age, BFP and sleep
      duration were associated with stroke prevalence. Corresponding measures for high
      risk population and risk factors should be strengthened to prevent and control
      the stroke.

PMID- 29334714
TI  - [Urinary iodine concentration status and its influencing factors of pregnant
      women in Yuhuan county, Zhejiang Province].

PMID- 29334715
TI  - [Analysis of HCV infection rate and its influence factors among drug users in
      Dehong Prefecture, Yunnan Province].

PMID- 29334716
TI  - [Analysis on surveillance data of immunization safety for varicella vaccine after
      the immunization strategy implemented].

PMID- 29334717
TI  - [The ten-year retrospect of nutrition and health status of pregnant women in
      China].
AB  - Improvement of the nutrition and health status of pregnant women should be one of
      the top priority strategies of improving the physical fitness of next generation
      and reserve of talented person for national sustainable development. This paper
      reviews the nutrition and health status of pregnant women in China over the
      recent ten years and discusses the underlying factors and changing trends. The
      most popular nutrition-related problem is dietary imbalance, and many
      micronutrient intakes are lower than the recommended dietary intakes or adequate
      intakes, and some of nutrient intakes are still at a very low level for a long
      time such as vitamin D and calcium. The nutrition-related health problems are
      mainly anemia, vitamin D and vitamin A deficiencies; iodine intake is not in
      optimal state with a large proportion of inadequate and individual cases facing
      excessive intake risk. Overweight and obesity, pregnancy complications such as
      gastrocnemius muscle spasms, pregnancy hypertensive disorders and gestational
      diabetes were prevalent among pregnant women. We should address both malnutrition
      and nutrition imbalance in the same time in order to improve the nutrition and
      health status of pregnant women, by developing and implementing relevant laws and
      regulations, giving higher attention to pregnant women with advanced age, which
      in turns prevent a variety of micronutrient deficiencies, reduce adverse pregnant
      outcomes, and improve nutrition and health status of maternal and child.

PMID- 29334718
TI  - [Diet and nutrition interventions prevent gestational diabetes mellitus].
AB  - Gestational diabetes mellitus (GDM) is one of the most common complications
      during pregnancy, with rising trend over the years. Dietary nutrient intake
      (protein, fat and fatty acids, carbohydrate, vitamin D, vitamin E, iron, zinc,
      selenium and inositol et al.), dietary pattern and probiotics may be related to
      GDM occurrence. Dietary factors are modifiable factors for preventing GDM. The
      study reviewed the roles of these dietary factors in preventing GDM. Results
      showed that plant-based dietary pattern may lower the risk of GDM and dietary
      pattern characterized with high animal protein, high fat and low carbohydrate may
      increase the risk of GDM. It warrants further studies that nutrient
      supplementation may prevent pregnant women from GDM. Diverse diet based on plant
      and cereal food should be promote for healthy and appropriate weight gain during
      pregnancy.

PMID- 29334719
TI  - [Human papillomavirus infection and vaccination].
AB  - Human papillomavirus (HPV) is an infection that can be sexually transmitted and
      result in health consequences. Persistent high-risk HPV infection can lead to
      various cancers and is the essential cause of cervical cancer. HPV vaccine can
      prevent the HPV infection and thus the incidence of cervical cancer. In this
      review we introduced the prevalence of HPV infection and vaccination, and the
      prevention and early detection of cervical cancer. We also introduced the present
      knowledge and awareness of HPV infection and HPV vaccine in Chinese. Propaganda
      all over China should be performed on HPV vaccination to improve the vaccination
      rate, thus preventing the incidence of cervical cancer.

PMID- 29334720
TI  - [Responding to national strategy demand for a new era, and grasping key problems
      of basic frontiers in preventive medicine--Shuangqing Forum (No. 192) of National
      Natural Science Foundation of China].

PMID- 29334721
TI  - Efficacy and safety of tocilizumab in Korean patients with active rheumatoid
      arthritis.
AB  - Background/Aims: To investigate the efficacy and safety of tocilizumab (TCZ)
      humanized anti-interleukin-6 receptor monoclonal antibody, in Korean patients
      with active rheumatoid arthritis (RA) refractory to conventional disease
      modifying anti-rheumatic drugs (DMARDs) including methotrexate (MTX). Methods:
      The main study was a 24-week, randomized, double-blind, controlled trial that was
      followed by a 48-week, open-labeled, extension phase. TCZ (8 mg/kg) or placebo
      was intravenously administered every 4 weeks. Results: Those treated with TCZ
      showed more favorable outcomes in terms of 20% according to the American College
      of Rheumatology response criteria (ACR20) and ACR50 responses, individual
      parameters of ACR core set, disease activity score in 28 joints (DAS28)
      remission, and European League Against Rheumatism (EULAR) response at week 24.
      These improvements were maintained or increased during the extension period.
      DAS28 remission at week 72 was associated with EULAR good response at week 12.
      The patients who experienced any adverse event (AE) were more frequent in the TCZ
      group compared to the placebo group. Most AEs were mild or moderate in intensity,
      although TCZ therapy had possible AEs including serious infection, abnormal liver
      function, and atherogenic lipid profile. Conclusions: TCZ infusion add-on is
      highly efficacious and well-tolerated in Korean patients with active RA
      refractory to conventional DMARDs including MTX. EULAR good response at week 12
      could predict DAS28 remission at week 72.

PMID- 29334722
TI  - Comparison of the morphologic criteria (RECIST) and metabolic criteria (EORTC and
      PERCIST) in tumor response assessments: a pooled analysis.
AB  - Background/Aims: The Positron Emission Tomography Response Criteria in Solid
      Tumors (PERCIST) or European Organization for Research and Treatment of Cancer
      (EORTC) criteria are used to assess metabolic tumor responses. However, tumor
      responses have shown considerable discrepancies between the morphologic criteria
      (Response Evaluation Criteria in Solid Tumors [RECIST]) and metabolic criteria.
      We performed this pooled study to compare the RECIST and metabolic criteria in
      the assessment of tumor responses. Methods: Electronic databases were searched
      for eligible articles with the terms "RECIST," "PERCIST," or "EORTC criteria."
      The level of concordance in the tumor responses between the two criteria was
      estimated using kappa statistics. Results: A total of 216 patients were collected
      from eight studies comparing the RECIST and EORTC criteria. The agreement of
      tumor responses between the two criteria was moderate (kappa = 0.447). Eighty-six
      patients (39.8%) showed disagreement: tumor response was upgraded in 70 patients
      and downgraded in 16 when adopting the EORTC criteria. The EORTC criteria
      significantly increased the overall response rate (53% vs. 28%, p < 0.0001). The
      agreement of tumor responses between the RECIST and PERCIST was deemed fair
      (kappa = 0.389). Of 407 patients from nine studies, 181 (44.5%) showed a
      discrepancy: using the PERCIST, tumor response were upgraded in 151 patients and
      downgraded in 30. When adopting the PERCIST, the overall response rate was also
      significantly increased from 30% to 55% (p < 0.0001). Conclusions: This pooled
      analysis demonstrates that the concordance of tumor responses between the
      morphologic criteria and metabolic criteria is not excellent. When adopting the
      metabolic criteria instead of the RECIST, overall response rates were
      significantly increased.

PMID- 29334723
TI  - Methacholine bronchial provocation test in patients with asthma: serial
      measurements and clinical significance.
AB  - Background/Aims: The methacholine bronchial provocation test (MBPT) is used to
      detect and quantify airway hyper-responsiveness (AHR). Since improvements in the
      severity of asthma are associated with improvements in AHR, clinical studies of
      asthma therapies routinely use the change of airway responsiveness as an
      objective outcome. The aim of this study was to assess the relationship between
      serial MBPT and clinical profiles in patients with asthma. METHODS: A total of
      323 asthma patients were included in this study. The MBPT was performed on all
      patients beginning at their initial diagnosis until asthma was considered
      controlled based on the Global Initiative for Asthma guidelines. A responder was
      defined by a decrease in AHR while all other patients were considered non
      responders. RESULTS: A total of 213 patients (66%) were responders, while 110
      patients (34%) were non-responders. The responder group had a lower initial PC20
      (provocative concentration of methacholine required to decrease the forced
      expiratory volume in 1 second by 20%) and longer duration compared to the non
      responder group. Members of the responder group also had superior qualities of
      life, compared to members of the non-responder group. Whole blood cell counts
      were not related to differences in PC20; however, eosinophil concentration was.
      No differences in sex, age, body mass index, smoking history, serum
      immunoglobulin E, or frequency of acute exacerbation were observed between
      responders and non-responders. Conclusions: The initial PC20, the duration of
      asthma, eosinophil concentrations, and quality-of-life may be useful variables to
      identify improvements in AHR in asthma patients.

PMID- 29334724
TI  - Disparity in Crohn's disease activity between home and clinics is associated with
      unscheduled hospital visits due to disease flares.
AB  - BACKGROUND/AIMS: E-health technologies have been implemented for the management
      of Crohn's disease (CD). We aimed to identify differences between patient
      activities at home and at routine clinic visits using a web-based self-reporting
      CD symptom diary (CDSD) and to determine the impact of this disparity on clinical
      outcomes. METHODS: Patients with CD from three tertiary hospitals were invited to
      assess their symptoms at least once a week using CDSD. We identified patients who
      showed disparities in disease activity (high activity at home but normal at the
      next hospital visit) and evaluated clinical outcomes of these patients such as
      unscheduled visits due to flares using Kaplan-Meier analyses. RESULTS: One
      hundred and forty-three patients recorded their symptoms weekly for at least 3
      consecutive months and were included. Forty-eight patients (33.6%) showed
      disparate disease activities between at home and at the next outpatient clinic
      visit. The cumulative risk of unscheduled visits was significantly higher in this
      disparity group than in the concordant group (p = 0.001). Disparity in activity
      (p = 0.003), and anti-tumor necrosis factor use (p = 0.002) were independent risk
      factors of unscheduled visits due to disease flares. CONCLUSION: Disparity in
      disease activity is considerable in CD patients and is related to the risk of
      unscheduled hospital visit.

PMID- 29334725
TI  - Physical activity in chronic obstructive pulmonary disease: clinical impact and
      risk factors.

PMID- 29334726
TI  - Procalcitonin in bloodstream infections: beyond its role as a marker of clinical
      algorithm to reduce antimicrobial overuse.

PMID- 29334727
TI  - ApoB/ApoA-I ratio is independently associated with carotid atherosclerosis in
      type 2 diabetes mellitus with well-controlled LDL cholesterol levels.
AB  - BACKGROUND/AIMS: This study aimed to investigate whether the apolipoprotein (Apo)
      B/ApoA-I ratio is associated with carotid intima-media thickness (CIMT) in type 2
      diabetes mellitus (T2DM) subjects with low density lipoprotein cholesterol (LDL
      C) levels less than 100 mg/dL. METHODS: This cross-sectional study included 845
      subjects aged with T2DM 40 to 75 years who had visited Huh's Diabetes Center in
      Seoul, Republic of Korea for CIMT measurement. Traditional fasting lipid
      profiles, ApoB and ApoA-I levels were examined. CIMT was measured at three points
      on the far wall of 1 cm long section of the common carotid artery in the
      proximity of the carotid bulb. The mean value of six measurements from right and
      left carotid arteries were used as the mean CIMT. In this study, carotid
      atherosclerosis was defined as having a focal plaque or diffuse thickening of the
      carotid wall (mean CIMT >= 1.0 mm). RESULTS: The prevalence of carotid
      atherosclerosis increased with ApoB/ApoA-I ratio. The ApoB/ApoA-I ratio,
      expressed as both quartiles (odds ratio [OR], 2.14; 95% confidence interval [CI],
      1.21 to 3.79; p for trend = 0.014) and continuous values (OR, 10.05; 95% CI, 3.26
      to 30.97; p < 0.001), was significantly associated with a higher risk for carotid
      atherosclerosis, regardless of conventional cardiovascular disease risk factors.
      The optimal ApoB/ApoA-I ratio cutoff value for detecting carotid atherosclerosis
      was 0.57, based on receiver operating characteristic curve analysis with a
      sensitivity of 58.0% and a specificity of 55.1%. CONCLUSIONS: A high ApoB/ApoA-I
      ratio was significantly associated with carotid atherosclerosis in T2DM patients
      with LDL-C levels less than 100 mg/dL.

PMID- 29334728
TI  - Changing treatment paradigms for the management of inflammatory bowel disease.
AB  - Inflammatory bowel disease (IBD) is a chronic and progressive inf lammatory
      condition of the gastrointestinal tract causing bowel damage, hospitalizations,
      surgeries, and disability. Although there has been much progress in the
      management of IBD with established and evolving therapies, most current
      approaches have failed to change the natural course. Therefore, the treatment
      approach and follow-up of patients with IBD have undergone a significant change.
      Usage of immunosuppressants and/or biologics early during the course of the
      disease, known as top-down or accelerated step-up approach, was shown to be
      superior to conventional management in patients who had been recently diagnosed
      with IBD. This approach can be applied to selected groups based on prognostic
      factors to control disease activity and prevent progressive disease. Therapeutic
      targets have been shifted from clinical remission mainly based on symptoms to
      objective parameters such as endoscopic healing due to the discrepancies observed
      between symptoms, objectively evaluated inf lammatory activity, and intestinal
      damage. The concept of treat-to-target in IBD has been supported by population
      based cohort studies, post hoc analysis of clinical trials, and meta-analysis,
      but more evidence is needed to support this concept to be applied to the clinical
      practice. In addition, individualized approach with tight monitoring of non
      invasive biomarker such as C-reactive protein and fecal calprotectin and drug
      concentration has shown to improve clinical and endoscopic outcomes. An
      appropriate de-escalation strategy is considered based on patient demographics,
      disease features, current disease status, and patients' preferences.

PMID- 29334729
TI  - Polyoxygenated Cyclohexenoids with Promising alpha-Glycosidase Inhibitory
      Activity Produced by Phomopsis sp. YE3250, an Endophytic Fungus Derived from
      Paeonia delavayi.
AB  - Seven new polyoxygenated cyclohexenoids, namely, phomopoxides A-G (1-7), were
      isolated from the fermentation broth extract of an endophytic fungal strain
      Phomopsis sp. YE3250 from the medicinal plant Paeonia delavayi Franch. The
      structures of these compounds were established by spectroscopic interpretation.
      The absolute configurations of compounds 1 and 4 were confirmed by X-ray
      crystallographic analysis and chemical derivative approach. All isolated
      compounds showed weak cytotoxic activities toward three human tumor cell lines
      (Hela, MCF-7, and NCI-H460) and weak antifungal activities against five
      pathogenic fungi (Candida albicans, Aspergillus niger, Pyricularia oryzae,
      Fusarium avenaceum, and Hormodendrum compactum). In addition, compounds 1-7
      showed a promising alpha-glycosidase inhibitory activity with IC50 values of
      1.47, 1.55, 1.83, 2.76, 2.88, 3.16, and 2.94 mM, respectively, as compared with a
      positive control of acarbose (IC50 = 1.22 mM).

PMID- 29334730
TI  - Decomposition Pathways of Titanium Isopropoxide Ti(OiPr)4: New Insights from UV
      Photodissociation Experiments and Quantum Chemical Calculations.
AB  - The UV-photodissociation at 266 nm of a widely used TiO2 precursor, titanium
      tetraisopropoxide (Ti(OiPr)4, TTIP), was studied under molecular-beam conditions.
      Using the MS-TOF technique, atomic titanium and titanium(II) oxide (TiO) were
      detected among the most abundant photofragments. Experimental results were
      rationalized with the aid of quantum chemical calculations (DLPNO-CCSD(T) and
      DFT). Contrary to the existing data in the literature, the new four-centered
      acetone-elimination reaction was found to be the primary decomposition process of
      TTIP. According to computational results, the effective activation barrier of
      this channel was ~49 kcal/mol, which was ~13 kcal/mol lower than that of the
      competing propylene elimination. The former process, followed by the dissociative
      loss of an H atom, was a dominating channel of TTIP unimolecular decay. The
      sequential loss of isopropoxy moieties via these two-step processes was supposed
      to produce the experimentally observed titanium atoms. In turn, the combination
      of these reactions with propylene elimination can lead to another detected
      species, TiO. These results indicate that the existing mechanisms of TTIP thermal
      and photoinitiated decomposition in the chemical-vapor deposition (CVD) of
      titanium dioxide should be reconsidered.

PMID- 29334731
TI  - Validity of Measuring Metallic and Semiconducting Single-Walled Carbon Nanotube
      Fractions by Quantitative Raman Spectroscopy.
AB  - Although it is known that the Raman spectroscopic signature of single-walled
      carbon nanotubes (SWCNTs) is highly chirality dependent, using Raman spectroscopy
      with several laser excitations as a tool for quantifying fraction of either
      metallic or semiconducting nanotubes in a sample has become a widely used
      analytical method. In this work, using the electron diffraction technique as a
      basis, we have examined the validity of Raman spectroscopy for quantitative
      evaluation of metallic fractions (M%) in single-walled carbon nanotube samples.
      Our results show that quantitative Raman spectroscopic evaluations of M% by using
      several discrete laser lines, either by using integrated intensities of chirality
      associated radial breathing modes (RBMs) or, as has been more commonly utilized
      in recent studies, by statistically counting the numbers of RBMs can be
      misrepresentative. Specifically, we have found that the occurrence numbers of
      certain types of RBMs in Raman spectral mapping depend critically on the diameter
      distribution, resonant coupling between transition energies and excitation laser
      energy, and the chirality-dependent Raman scattering cross sections rather than
      simply on the metallic and semiconducting SWCNT fractions. These dependencies are
      similar to those observed in the integrated intensities of RBMs. Our findings
      substantially advance the understanding of the proper use of Raman spectroscopy
      for carbon nanotube quantification, which is important for carbon nanotube
      characterization and crucial to guide research in SWCNT growth and their
      applications.

PMID- 29334732
TI  - Fine Art of Thermoelectricity.
AB  - A detailed study of hitherto unknown electrical and thermoelectric properties of
      graphite pencil traces on paper was carried out by measuring the Hall and Seebeck
      effects. We show that the combination of pencil-drawn graphite and brush-painted
      poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) films on
      regular office paper results in extremely simple, low-cost, and environmentally
      friendly thermoelectric power generators with promising output characteristics at
      low-temperature gradients. The working characteristics can be improved even
      further by incorporating n-type InSe flakes. The combination of pencil-drawn n
      InSe:graphite nanocomposites and brush-painted PEDOT:PSS increases the power
      output by 1 order of magnitude.

PMID- 29334733
TI  - Surface Functionalization with Carboxylic Acids by Photochemical Microcontact
      Printing and Tetrazole Chemistry.
AB  - In this paper, we show that carboxylic acid-functionalized molecules can be
      patterned by photochemical microcontact printing on tetrazole-terminated self
      assembled monolayers. Upon irradiation, tetrazoles eliminate nitrogen to form
      highly reactive nitrile imines, which can be ligated with several different
      nucleophiles, carboxylic acids being the most reactive. As a proof of concept, we
      immobilized trifluoroacetic acid to monitor the reaction with X-ray photoelectron
      spectroscopy. Moreover, we also immobilized peptides and fabricated carbohydrate
      lectin as well as biotin-streptavidin microarrays using this method. Surface
      patterning was demonstrated by fluorescence microscopy and time-of-flight
      secondary ion mass spectrometry.

PMID- 29334735
TI  - Complex Dynamics of Photo-Switchable Guest Molecules in All-Optical Poling Close
      to the Glass Transition: Kinetic Monte Carlo Modeling.
AB  - We study theoretically the kinetics of noninteracting photoswitchable guest
      molecules (model azo-dye) dispersed at low concentration in host (model polymer
      matrix) in the all-optical poling process close to the glass transition
      temperature Tg. We modify kinetic Monte Carlo model used in our previous studies
      of nonlinear optical processes in host-guest systems. The polymer matrix is
      simulated using the bond-fluctuation model. The kinetics of multiple trans-cis
      trans cycles is formulated in terms of transition probabilities which depend on
      local free volume in the matrix and its dynamics. Close to Tg, the buildup of
      polar order, monitored in terms of angular probability density functions, follows
      a power-law in time while the evolution of the nonlinear susceptibilities related
      to second harmonic generation effect follows the stretched-exponential law. This
      complex dynamics of guest molecules implies the presence of dynamic
      heterogeneities of the matrix in space and time which spread the complexity from
      the matrix to the otherwise simple dynamics of noninteracting guest molecules. A
      qualitative physical picture of mosaic-like states-intertwined areas of free- and
      hindered angular motion of guest molecules-is proposed and the role of related
      short and longer scales in space for the promotion of complex dynamics of guest
      molecules is discussed. A brief comparison of the theory to available
      experimental data is given.

PMID- 29334734
TI  - A Method for Selective Depletion of Zn(II) Ions from Complex Biological Media and
      Evaluation of Cellular Consequences of Zn(II) Deficiency.
AB  - We describe the preparation, evaluation, and application of an S100A12 protein
      conjugated solid support, hereafter the "A12-resin", that can remove 99% of
      Zn(II) from complex biological solutions without significantly perturbing the
      concentrations of other metal ions. The A12-resin can be applied to selectively
      deplete Zn(II) from diverse tissue culture media and from other biological
      fluids, including human serum. To further demonstrate the utility of this
      approach, we investigated metabolic, transcriptomic, and metallomic responses of
      HEK293 cells cultured in medium depleted of Zn(II) using S100A12. The resulting
      data provide insight into how cells respond to acute Zn(II) deficiency. We expect
      that the A12-resin will facilitate interrogation of disrupted Zn(II) homeostasis
      in biological settings, uncovering novel roles for Zn(II) in biology.

PMID- 29334736
TI  - Hydration Behavior along the Folding Pathways of Trpzip4, Trpzip5 and Trpzip6.
AB  - The microscopic properties of water confined within different segments of Trpzip4
      (TZ4), Trpzip5 (TZ5), and Trzpip6 (TZ6) have been compared for all the states
      characterized along their folding pathways. In particular, structural ordering,
      energetics, and dynamics of water have been examined as the peptide unfolds along
      the free energy landscape. It is observed that the structuring of tetrahedral
      network as well as translational and rotational motions of hydration waters
      confined within the strands and the turn regions are very different, revealing
      motional heterogeneity in small 16-residue trpzips. The polar and charged groups
      present at the peptide surface anchor to water molecules through hydrogen bonds
      and are responsible for differential hydration among various segments of the
      peptide, which is found to be correlated to their hydropathy values. The coherent
      collective dynamics of water is strongly coupled with conformational changes in
      the peptide since the trends observed in most of the computed quantities are in
      accordance with the folded and unfolded states classified along the folding
      pathway for all trpzips. The hydration behavior conform to the heterogeneity
      observed in the free energy landscape of stable TZ4 with four unfolded states as
      compared to more flexible TZ5 and TZ6 with two unfolded states each, in addition
      to the folded state. The hydration waters are observed to regulate the protein
      dynamics by continuous fluctuations in hydrogen bond network involving lateral
      side chains that inject conformational motions in the peptide to facilitate its
      unfolding. The implications of mutations on various aspects of hydration water
      dynamics including their impact on structural and dynamic organization of
      hydrogen bonds are also highlighted. Our studies affirm that topology of the free
      energy landscape is shaped by both spatial organization and dynamic transitions
      in hydration waters in addition to the conformational fluctuations in the peptide
      along the folding pathway.

PMID- 29334737
TI  - Tubular Hybrids: A Nanoparticle-Molecular Network.
AB  - We report here a new methodology for the formation of freestanding nanotubes
      composed of individual gold nanoparticles (NPs) cross-linked by coordination
      complexes or porphyrin molecules using WS2 nanotubes (INT-WS2) as a template. Our
      method consists of three steps: (i) coverage of these robust inorganic materials
      with monodispersed and dense monolayers of gold NPs, (ii) formation of a
      molecular AuNP network by exposing these decorated tubes to solutions containing
      a ruthenium polypyridyl complex or meso-tetra(4-pyridyl)porphyrin, and (iii)
      removal of the INT-WS2 template with a hydrogen peroxide solution.
      Nanoindentation of the template-free AuNP tubes with atomic force microscopy
      indicates a radial elastic modulus of 4 GPa. The template-free molecular AuNP
      tubes are characterized using scanning and transmission electron microscopy,
      energy-dispersive X-ray spectroscopy, and micro-Raman spectroscopy. The
      methodology provides a convenient and scalable strategy for the realization of
      molecular AuNP tubes with a defined length and diameter, depending on the
      dimensions of the template.

PMID- 29334738
TI  - Quantitative Visualization of Salt Concentration Distributions in Lithium-Ion
      Battery Electrolytes during Battery Operation Using X-ray Phase Imaging.
AB  - A fundamental understanding of concentrations of salts in lithium-ion battery
      electrolytes during battery operation is important for optimal operation and
      design of lithium-ion batteries. However, there are few techniques that can be
      used to quantitatively characterize salt concentration distributions in the
      electrolytes during battery operation. In this paper, we demonstrate that in
      operando X-ray phase imaging can quantitatively visualize the salt concentration
      distributions that arise in electrolytes during battery operation. From
      quantitative evaluation of the concentration distributions at steady states, we
      obtained the salt diffusivities in electrolytes with different initial salt
      concentrations. Because of no restriction on samples and high temporal and
      spatial resolutions, X-ray phase imaging will be a versatile technique for
      evaluating electrolytes, both aqueous and nonaqueous, of many electrochemical
      systems.

PMID- 29334739
TI  - Microfluidic-Assisted Production of Size-Controlled Superparamagnetic Iron Oxide
      Nanoparticles-Loaded Poly(methyl methacrylate) Nanohybrids.
AB  - In this paper, superparamagnetic iron oxide nanoparticles (SPIONs, around 6 nm)
      encapsulated in poly(methyl methacrylate) nanoparticles (PMMA NPs) with
      controlled sizes ranging from 100 to 200 nm have been successfully produced. The
      hybrid polymeric NPs were prepared following two different methods: (1)
      nanoprecipitation and (2) nanoemulsification-evaporation. These two methods were
      implemented in two different microprocesses based on the use of an impact jet
      micromixer and an elongational-flow microemulsifier. SPIONs-loaded PMMA NPs
      synthesized by the two methods presented completely different physicochemical
      properties. The polymeric NPs prepared with the micromixer-assisted
      nanoprecipitation method showed a heterogeneous dispersion of SPIONs inside the
      polymer matrix, an encapsulation efficiency close to 100 wt %, and an irregular
      shape. In contrast, the polymeric NPs prepared with the microfluidic-assisted
      nanoemulsification-evaporation method showed a homogeneous dispersion, an almost
      complete encapsulation, and a spherical shape. The properties of the polymeric
      NPs have been characterized by dynamic light scattering, thermogravimetric
      analysis, and transmission electron microscope. In vitro cytotoxicity assays were
      also performed on the nanohybrids and pure PMMA NPs.

PMID- 29334740
TI  - Point of Departure.

PMID- 29334741
TI  - Accounts: 50 Years of a Great Idea.

PMID- 29334742
TI  - [Diagnostic and prognostic biomarkers in acute coronary syndrome].
AB  - Acute myocardial infarction (AMI) is an important cause of mortality and
      morbidity worldwide. Early diagnostics of this disease helps in the appropriate
      treatment of patients. Great attention is paid to the diagnostic and risk
      stratification of patients according to circulating biomarkers. There are a lot
      of scientific publications describing this topic. The aim of this article is to
      provide a comprehensive overview of the most important and most examined
      biomarkers in acute coronary syndrome. Meanwhile troponin takes a fundamental
      place for AMI diagnostic (mostly the high-sensitive methods) in preference to MB
      fraction of creatine kinase and myoglobin. The connection to a higher sudden
      death risk, reinfarcts and heart failure occurring was also proved by many other
      biomarkers. The most important of them are the natriuretic peptides, the C
      reactive protein, the heart fatty acid binding protein, the pregnancy-associated
      plasma protein-A, CD146, cystatin C, NGAL, copeptin, MR-proadrenomedullin, and
      the growth differentiation factor-15. More prospective randomized studies are
      needed for the further use of these other biomarkers in clinical practice.Key
      words: acute coronary syndrome - biomarkers.

PMID- 29334744
TI  - [Selenium treatment in thyreopathies].
AB  - Selenium (latin Selenium) is a micronutrient embedded in several proteins. In
      adults, the thyroid is the organ with the highest amount of selenium per gram of
      tissue. Selenium levels in the body depend on the characteristics of the
      population and its diet and geographic area. In the thyroid, selenium is required
      for the antioxidant function and for the metabolism of thyroid hormones. The
      literature suggests that selenium supplementation of patients with Hashimotos
      thyroiditis is associated with a reduction in antithyroperoxidase antibody
      levels. Selenium supplementation also in mild Graves orbitopathy is associated
      with delayed progression of ocular disorders. As a consequence of this
      observation The European Group on Graves Orbitopathy recommend six months
      selenium preparates supportive therapy for patients with mild form of Graves
      orbitopathy.Key words: Graves-Basedows disease - Hashimotos thyroiditis -
      selenium - supplementation.

PMID- 29334743
TI  - [Adiponectin in patients with metabolic syndrome and diseases of the liver, bile
      ducts and pancreas].
AB  - Epidemiological data show that the metabolic syndrome can be diagnosed in up to
      30 % of the population. Regarding 5 components of the metabolic syndrome, three
      of them, in case of positivity (visceral obesity, arterial hypertension,
      hypertriglyceridemia, changes of HDL-cholesterol levels and type 2 diabetes
      mellitus), are pathogenic factors which are the most frequently related to
      cardiovascular diseases, but currently they are also the focus of interest for
      gastroenterologists. The relationship between non-alcoholic hepatic steatosis,
      including non-alcoholic steatohepatitis, has been described. Less is known so far
      about the relation to the pancreas disease, particularly with respect to the
      status referred to as non-alcoholic fatty pancreas disease. The hormone
      selectively produced by adipose tissue is adiponectin. This protein is studied as
      a possible biomarker in people with metabolic syndrome, including obesity.
      Besides that, there is a question studied whether adiponectin can also play a
      significant role in the pathogenesis of diseases associated with fat building up
      in parenchymatous organs. Finding a reliable biomarker for patients with
      metabolic syndrome or diseases of the liver, biliary system and pancreas in
      relation to metabolic syndrome, presents a big challenge. And adiponectin is one
      of the promising biomarkers.Key words: adiponectin - biliary disease - metabolic
      syndrome - pancreatic steatosis - steatohepatitis.

PMID- 29334745
TI  - [Citalopram and QT prolongation].
AB  - In 2011/2012, the US Food and Drug Administration issued a warning about the
      effect of citalopram on the QT interval and decreased its dosing. Further studies
      addressing this issue have been published since then. The authors were interested
      to know whether or not the studies have furnished new information that could
      modify or further specify the FDA-issued recommendations. After analyzing the
      most relevant studies, the authors concluded that even papers published within
      the last 5 years confirmed that, of the SSRI class of drugs, citalopram prolongs
      the QT interval most significantly. While the QT interval prolongation in young
      and otherwise healthy individuals is small and treatment with citalopram
      relatively safe, in elderly comorbid patients with polypharmacy, use of even
      currently recommended doses may result in significant QT interval prolongation.
      Hence, the decision about future therapy will depend on the degree of risk of
      each individual patient. Judging by the most recent data, citalopram is not more
      effective compared with the other SSRIs. As a result, therapy with citalopram
      will presumably show a declining trend, particularly in elderly patients.Key
      words: citalopram - escitalopram - QT interval - SSRI.

PMID- 29334746
TI  - [The current role of warfarin].
AB  - Well-managed warfarin therapy remains an important method of anticoagulation in
      the 21st century, despite the introduction of new antithrombotics into the
      clinical practice. The main advantages of warfarin are decades of treatment
      experience, the possibility to monitor its anticoagulant effect using the INR and
      the last, but not least, the low cost. Currently, approximately 75 % of
      anticoagulated patients in the Czech Republic are treated with warfarin and
      warfarin remains the only option for oral anticoagulant therapy in certain
      clinical conditions (particularly in patients with valvular atrial fibrillation
      or mechanical heart valves). For physicians across specialties it is still
      indispensable to master the basics of safe and effective warfarin therapy,
      including the management of treatment complications.Key words: anticoagulant
      therapy - INR - thrombosis - warfarin.

PMID- 29334747
TI  - [Drug induced tendon injury].
AB  - Tendon injury belongs to the less known side effects of some drugs, reported
      until recently only for glucocorticoids and fluoroquinolones. To date, some other
      classes of drugs such as statins, aromatase inhibitors, anabolic steroids,
      potentially causing tendon injury, have been added to the list. The authors
      discuss the most common clinical presentations, diagnosis, and management as well
      as latest experimental data regarding this issue. The most often, the Achilles
      tendon is affected, however, nearly every tendon of the entire body may be
      affected. Tendon rupture or drug induced tendinopathy should be strongly
      considered in those who have a tendon injury and have recently taken these
      drugs.Key words: anabolic steroids - aromatase inhibitors - fluoroquinolones -
      glucocorticoids - statins - tendon injury.

PMID- 29334748
TI  - [How to apply the ambulatory cardiovascular rehabilitation: guidelines of the
      Working group for cardiovascular rehabilitation at Slovak Society of Cardiology].
AB  - Authors have proposed a concept of guidelines for applying the ambulatory complex
      cardiovascular rehabilitation (ACCVR) into the clinical practice in Slovakia. As
      a background they have used an actual cardiovascular mortality and morbidity data
      from home country and abroad as well. They emphasize the non-optimal situation in
      this aspect which may not be solved by the increasing supporting the invasive
      revascularization methods and by the intensifying pharmacotherapy only, because
      the favourable effects of these procedures is timely missing if it is not
      accompanied by the therapeutic lifestyle changes. In this proposal the ACCVR is
      considered not as a regular, controlled physical training only, but there is
      included patient's education, relaxation, stress management, behavioral changes
      and possible social support too. At the end of one 3 months lasting cycle of
      ACCVR there is subsumed a final test oriented on patient's education and physical
      fitness levels and the continuing long-term contacts with him during following
      home-based training. Main parts of the concept are the concrete conditions which
      should by fulfilled as for as a personal, space and device equipment needed for
      accreditation so called cardiology stationary for ACCVR activities (in connection
      with cardiology department for out patients). Moreover, there are also included
      practical guidelines how to do patient's stratification, how to send the patients
      to stationary, indications and contraindications, establishing of the training
      heart rate and training load, the composition of one cycle 3 months lasting,
      application of the progressive aerobic and resistance training and how to
      continue in home-based training. At the end the authors have proposed conditions
      which are needed to fulfil for a successful implementation of ACCVR into the
      health care system.Key words: cardiovascular rehabilitation for out patients -
      exercise training - home based training with telemonitoring control - progressive
      resistance training - relaxation and stress management.

PMID- 29334749
TI  - [Unusual history of Wilson disease: a case report and review of the literature].
AB  - Wilson disease (WD) belongs to autosomal recessive genetic metabolic disorders
      with gene mutation ATP7B located on 13th chromosome. The enzyme ATPase plays an
      important role in WD. It facilitates excretion of copper into bile. This gene is
      responsible for modification of apoceruloplasmin. In this disease, it leads to
      insufficient release of copper from organism and accumulation of copper in organs
      such as liver, brain which can cause dysfunction of a certain organ. According to
      specific symptoms, we can divide WD into psychiatric, neurologic or hepatic form.
      The WD usually manifests between 15 and 25 years of age. Hepatic form often
      occurs sooner, on the contrary, the neurological variant usually occur during the
      later stages. We present a case report of 45-years-old woman with atypical
      medical history of WD, in which the diagnostic process was very long and had
      interdisciplinary character.Key words: brain - copper - diagnostic - genetics -
      liver - panda - Wilson disease.

PMID- 29334750
TI  - [Remission of steroid-resistant Stills disease treated with anakinra, evidenced
      by FDG-PET/CT examination: case report].
AB  - After elimination of infectious causes, neoplastic causes and the systemic
      autoimmune disease of connective tissue, a patient with high fevers over 39 
      degrees C was diagnosed with Stills disease. High doses of prednisone led to
      resolution of symptoms, however after reducing the doses of prednisone to 15 mg,
      high fevers over 39  degrees C returned, as well as joint pains. The high doses
      of prednisone led to decompensation of diabetes mellitus even with 4 daily
      insulin dosages. Therefore it was proceeded to regular subcutaneous
      administration of anakinra once a day. Anakinra enabled the reduction of
      prednisone to as much as the currently administered 2.5 mg a day, but it has not
      so far allowed for removing glucocorticoids from the treatment completely.
      Activity of the disease is shown by the findings within the FDG-PET/CT
      examination. At the time of maximum activity of the disease there was distinct
      lymphadenopathy with pathological accumulation of FDG visible as well as
      increased accumulation of FDG in the hematopoietic bone marrow. As the disease
      activity decreased, the size of nodules regressed and FDG accumulation in both
      the lymphatic nodes and bone marrow declined. FDG-PET/CT is a suitable method for
      monitoring the activity of Stills disease.Key words: anakinra - Adult-onset
      Stills disease.

PMID- 29334751
TI  - Pursuing excellence in ERCP.
AB  - The term "ERCP cannulation" returns 1,563 items in Pubmed. In 1980 there were 7
      papers, and 92 were included in 2015. Any gastroenterologist knows ERCP is often
      a complex procedure, at times with uncertain results, that unfortunately leads
      every so often to lawsuits. Most issues derive from attempts at biliary
      cannulation, despite the improved instruments available since the days of the
      first sphincterotomy back in 1974. The initial priority goal of ERCP learning is
      a satisfactory rate of choledochal cannulation. Such rate has been somewhat
      arbitrarily set as at least 80% of successful biliary access.

PMID- 29334752
TI  - The road to registration: Aboriginal and Torres Strait Islander health
      practitioner training in north Queensland.
AB  - CONTEXT: In 2012, the new profession of Aboriginal and Torres Strait Islander
      health practitioner (ATSIHP) was registered under the Health Practitioner
      Regulation National Law Act 2009. The project in this present study evolved out
      of the Australian Government?'s recognition of the need for the existing
      Indigenous health worker (IHW) workforce to meet the minimum qualification
      requirements for registration as ATSIHPs through recognition of prior learning
      and/or further education. A total of 53 IHWs participated in the upskilling
      project between June 2014 and June 2015, with approximately 200 IHWs from
      Queensland expressing an interest in undertaking the training. This demonstrated
      a clear need for further training programs such as this one. The project was
      coordinated by the Indigenous Health Unit at James Cook University (JCU) with
      training being delivered by TAFE Cairns in collaboration with the College of
      Medicine and Dentistry, JCU. Students travelled from as far north as the Torres
      Strait and as far west as Mount Isa. ISSUES: The key issues for discussion were
      associated with the ATSIHP role being relatively new including the limited
      preparedness of training providers to deliver the upgraded qualification
      requirements and uncertainty about the registration process. Compounding this was
      a general undervaluing and underutilisation of the IHW role within the current
      primary healthcare system. Other challenges included the variations of IHW roles,
      scope of practice and educational standards held by individuals, as well as the
      associated complexities of providing training to IHWs from the large and diverse
      geographic area that is rural and remote Australia. Program and student
      evaluation was undertaken with each of the three cohorts via a course experience
      questionnaire, TAFE evaluation forms and opportunistic student feedback. LESSONS
      LEARNED: Lessons learned as a result of this project include the need to continue
      to recognise and promote understanding of the contribution that IHW/ATSIHPs make
      in improving health, the importance of conducting a comprehensive student
      selection process, the benefits of working collaboratively between the university
      and vocational education training sectors, the need to continue to strengthen
      partnerships between higher education and health industry, the need for flexible
      funding and training models that enable adequate learning support, and the
      identification of a significant unmet training need.

PMID- 29334753
TI  - Physicians' Perceptions of Hope and How Hope Informs Interactions With Patients:
      A Qualitative, Exploratory Study.
AB  - OBJECTIVES: Today some studies of physicians' perceptions of hope are available,
      but not studies of how hope informs patient care. The objectives of this
      qualitative study were to describe the ways physicians conceptualize hope and how
      these may inform interactions with their patients. METHODS: Ten physicians
      working in a large tertiary care teaching hospital were interviewed. They
      represented palliative care, oncology, and 7 other specialties. Minimal amount of
      background information was collected. In-depth interviews were conducted during
      spring of 2016. Open coding and the constant comparison method were used to
      identify emerging themes from the transcribed data. Validation method included
      member checking. RESULTS: Hope was defined as an abstract, evolving concept
      characterized by future-oriented wishes; offering possibilities for reframing and
      shaping new meaning; an attitude of positivity or optimism; an attribute of the
      human condition with emotional and relational roots; and as a response to the
      existential inevitability of suffering and death. Three themes describing hope
      emerged: "assessing hope," "fostering and sustaining hope," and "attributes and
      outcomes of hope." CONCLUSIONS: The findings show how physicians conceptualize
      hope and how these conceptions differ in the empirical light of the study.
      Physicians' perceptions of "hope" may evolve when entering into a therapeutic
      relationship exploring the needs and desires of patients. Physicians'
      perspectives about "hope" may at times not be solely their own but are those of
      their patients and thus resulting in an amalgamation, or a rebuilding/rekindling
      of hope amidst hopelessness, that suits a particular relationship.

PMID- 29334754
TI  - High Neutrophil to Lymphocyte Ratio Is Associated With Symptomatic and Ruptured
      Thoracic Aortic Aneurysm.
AB  - The predictive value of the neutrophil to lymphocyte ratio (NLR) has been
      demonstrated in several cardiovascular diseases. The aim of our study was to
      investigate the association between the preoperative NLR and aneurysm
      characteristics as well as 30-day postoperative morbidity and mortality in
      patients with thoracic aortic aneurysm (TAA) undergoing aortic surgical repair.
      Consecutive patients (n = 75) with TAA were retrospectively included over a 10
      year period. Clinical characteristics, aneurysm characteristics, and 30-day
      postoperative outcome were recorded. The median age of patients was 71 (67-80)
      years. The median preoperative NLR was 3.5 (2.3-5.8). The proportion of
      asymptomatic TAA was significantly lower in patients with an NLR > 3.5 compared
      with those with an NLR < 3.5 (52.6% vs 75.7%; P = .054). The proportion of
      patients with pain or with ruptured TAA was significantly higher in patients with
      an NLR > 3.5 compared with those with NLR < 3.5 (42.1% vs 16.2%; P = .022 and
      26.3% vs 2.7%; P = .007, respectively). No significant difference was observed
      regarding the 30-day overall postoperative mortality and morbidity. The
      preoperative NLR did not correlate with TAA diameter. A high preoperative NLR is
      significantly associated with symptomatic and ruptured TAA, suggesting a
      potential interest as a marker and/or player in the disease.

PMID- 29334755
TI  - Neuropathy in Diabetes: "One Cannot Begin It Too Soon".

PMID- 29334756
TI  - Thioredoxin-1 Negatively Modulates ADAM17 Activity Through Direct Binding and
      Indirect Reductive Activity.
AB  - AIMS: A disintegrin and metalloprotease 17 (ADAM17) modulates signaling events by
      releasing surface protein ectodomains such as TNFa and the EGFR-ligands. We have
      previously characterized cytoplasmic thioredoxin-1 (Trx-1) as a partner of ADAM17
      cytoplasmic domain. Still, the mechanism of ADAM17 regulation by Trx-1 is
      unknown, and it has become of paramount importance to assess the degree of
      influence that Trx-1 has on metalloproteinase ADAM17. RESULTS: Combining
      discovery and targeted proteomic approaches, we uncovered that Trx-1 negatively
      regulates ADAM17 by direct and indirect effect. We performed cell-based assays
      with synthetic peptides and site-directed mutagenesis, and we demonstrated that
      the interaction interface of Trx-1 and ADAM17 is important for the negative
      regulation of ADAM17 activity. However, both Trx-1K72A and catalytic site mutant
      Trx-1C32/35S rescued ADAM17 activity, although the interaction with Trx-1C32/35S
      was unaffected, suggesting an indirect effect of Trx-1. We confirmed that the Trx
      1C32/35S mutant showed diminished reductive capacity, explaining this indirect
      effect on increasing ADAM17 activity through oxidant levels. Interestingly, Trx
      1K72A mutant showed similar oxidant levels to Trx-1C32/35S, even though its
      catalytic site was preserved. We further demonstrated that the general reactive
      oxygen species inhibitor, Nacetylcysteine (NAC), maintained the regulation of
      ADAM17 dependent of Trx-1 reductase activity levels; whereas the electron
      transport chain modulator, rotenone, abolished Trx-1 effect on ADAM17 activity.
      INNOVATION: We show for the first time that the mechanism of ADAM17 regulation,
      Trx-1 dependent, can be by direct interaction and indirect effect, bringing new
      insights into the cross-talk between isomerases and mammalian metalloproteinases.
      CONCLUSION: This unexpected Trx-1K72A behavior was due to more dimer formation
      and, consequently, the reduction of its Trx-1 reductase activity, evaluated
      through dimer verification, by gel filtration and mass spectrometry analysis.
      Antioxid. Redox Signal. 29, 717-734.

PMID- 29334757
TI  - High Prevalence of Non-B HIV-1 Subtypes in Overseas Sailors and Prostitutes in
      Korea.
AB  - There have been no studies related to groups at the highest risk for HIV-1
      infection in Korea before 1993. In this study, for the first time, we report the
      distribution of HIV subtypes in overseas sailors (OSs) and prostitutes who worked
      in brothels near U.S. military bases in Korea. We retrospectively determined the
      sequences of nef in 131 patients using reverse transcription polymerase chain
      reaction (RT-PCR). These patients composed of 102 OSs, 14 OS spouses, and 15
      prostitutes. Phylogenetic analysis was performed using 128 Korean OSs, OS
      spouses, and prostitutes. The distribution of non-B subtypes (n = 105) was as
      follows: 39, CRF02_AG; 15, CRF01_AE; 7, A1; 7, A2; 6, D; 2, CRF06_cpx; 3, C; 6,
      G; 11, untypable; and 1 each for CRF09_cpx, CRF12_BF, CRF50_A1D, A3, AFG, H, F1,
      F2, and A. Of the 116 OSs and OS spouses, 101 (87%), 11 (9%), and 4 (3%) subjects
      had non-B, Western B, and Korean subclade B (KSB) HIV-1s, respectively. Among the
      15 prostitutes, 10 had Western B (67%), 4 non-B (27%), and 1 KSB (7%) HIV-1s. All
      14 couples, each comprising of an OS and his spouse, had the same subtype. KSB
      (5%) was detected in OSs and prostitutes in 1990 and 1994, respectively. Of the
      131 patients analyzed in this study, 105 (80%), 21 (16%), and 5 (4%) were
      infected with the non-B, Western B, and KSB subtypes of HIV, respectively. In
      future, these data may provide an important foundation for analysis of HIV-1
      subtypes in Korea.

PMID- 29334758
TI  - Anticancer Thiosemicarbazones: Chemical Properties, Interaction with Iron
      Metabolism, and Resistance Development.
AB  - SIGNIFICANCE: During the past decades, thiosemicarbazones were clinically
      developed for a variety of diseases, including tuberculosis, viral infections,
      malaria, and cancer. With regard to malignant diseases, the class of alpha-N
      heterocyclic thiosemicarbazones, and here especially 3-aminopyridine-2
      carboxaldehyde thiosemicarbazone (Triapine), was intensively developed in
      multiple clinical phase I/II trials. Recent Advances: Very recently, two new
      derivatives, namely COTI-2 and di-2-pyridylketone 4-cyclohexyl-4-methyl-3
      thiosemicarbazone (DpC) have entered phase I evaluation. Based on the strong
      metal-chelating/metal-interacting properties of thiosemicarbazones, interference
      with the cellular iron (and copper) homeostasis is assumed to play an important
      role in their biological activity. CRITICAL ISSUES: In this review, we summarize
      and analyze the data on the interaction of (alpha-N-heterocyclic)
      thiosemicarbazones with iron, with the special aim of bridging the current
      knowledge on their mode of action from chemistry to (cell) biology. In addition,
      we highlight the difference to classical iron(III) chelators such as
      desferrioxamine (DFO), which are used for the treatment of iron overload. FUTURE
      DIRECTIONS: We want to emphasize that thiosemicarbazones are not solely removing
      iron from the cells/organism. In contrast, they should be considered as iron
      interacting drugs influencing diverse biological pathways in a complex and multi
      faceted mode of action. Consequently, in addition to the discussion of
      physicochemical properties (e.g., complex stability, redox activity), this review
      contains an overview on the diversity of cellular thiosemicarbazone targets and
      drug resistance mechanisms. Antioxid. Redox Signal. 00, 000-000.

PMID- 29334759
TI  - Redox Nano-Architectures: Perspectives and Implications in Diagnosis and
      Treatment of Human Diseases.
AB  - SIGNIFICANCE: Efficient targeted therapy with minimal side-effects is the need of
      the hour. Locally altered redox state is observed in several human ailments, such
      as inflammation, sepsis, and cancer. This has been taken advantage of in
      designing redox-responsive nanodrug carriers. Redox-responsive nanosystems open a
      door to a multitude of possibilities for the control of diseases over other drug
      delivery systems. Recent Advances: The first-generation nanotherapy relies on
      novel properties of nanomaterials to shield the drug and deliver it to the
      diseased tissue or organ. The second generation is based on targeting the drug or
      diagnostic material to the diseased cell-specific receptors, or to a particular
      organ to improve the efficacy of the drug. The third and the latest generation of
      nanocarriers, the stimuli-responsive nanocarriers exploit the disease condition
      or environment to specifically deliver the drug or diagnostic probe for the best
      diagnosis and treatment. Several different kinds of stimuli such as temperature,
      magnetic field, pH, and altered redox state-responsive nanosystems have educed
      immense promise in the field of nanomedicine and therapy. CRITICAL ISSUES: We
      describe the evolution of nanomaterial since its inception with an emphasis on
      stimuli-responsive nanocarriers, especially redox-sensitive nanocarriers.
      Importantly, we discuss the future perspectives of redox-responsive nanocarriers
      and their implications. FUTURE DIRECTIONS: Redox-responsive nanocarriers achieve
      a near-to-zero premature release of the drug, thus avoiding off-site toxicity
      associated with the free drug. This bears great potential for the development of
      more effective drug delivery with better pharmacokinetics and pharmacodynamics.
      Antioxid. Redox Signal. 00, 000-000.

PMID- 29334760
TI  - Polymorphisms in Estrogen Synthesis Genes and Symptom Clusters During the
      Menopausal Transition and Early Postmenopause: Observations From the Seattle
      Midlife Women's Health Study.
AB  - During the menopausal transition and early postmenopause, participants in the
      Seattle Midlife Women's Health Study (SMWHS) experienced one of the three symptom
      severity clusters identified through latent class analysis: severe hot flashes
      with moderate sleep, mood, cognitive, and pain symptoms (high-severity hot
      flash); low-severity hot flashes with moderate levels of all other symptom groups
      (moderate severity); and low levels of all symptom groups (low severity). In an
      effort to determine whether gene polymorphisms were associated with these symptom
      severity classes, we tested associations between gene polymorphisms in the
      estrogen synthesis pathways (cytochrome P450 19 [CYP 19] and 17 beta
      hydroxysteroid dehydrogenase [ 17HSDB1]) and the three symptom severity clusters.
      SMWHS participants ( N = 137) recorded symptoms monthly in diaries and provided
      buccal smears for genotyping. Multilevel latent class analysis with multinomial
      regression was used to determine associations between gene polymorphisms and
      symptom severity clusters. Only the 17HSDB1 polymorphisms ( rs615942 and
      rs592389) were associated significantly with the high-severity hot flash cluster
      versus the low-severity symptom cluster. None of the polymorphisms was associated
      with the moderate-severity cluster versus the low-severity symptom cluster.
      Findings of associations of the 17HSDB1 polymorphisms with the high-severity hot
      flash symptom cluster are consistent with those of an association between 17HSDB1
      polymorphisms and hot flashes in the Study of Women and Health Across the Nation
      population and our previous findings of associations between these polymorphisms
      with greater estrone levels.

PMID- 29334761
TI  - Regulation of Cancer and Cancer-Related Genes via NAD.
AB  - SIGNIFICANCE: NAD+ is an essential redox cofactor in cellular metabolism and has
      emerged as an important regulator of a wide spectrum of disease conditions, most
      notably, cancers. As such, various strategies targeting NAD+ synthesis in cancers
      are in clinical trials. Recent Advances: Being a substrate required for the
      activity of various enzyme families, especially sirtuins and poly(adenosine
      diphosphate [ADP]-ribose) polymerases, NAD+-mediated signaling plays an important
      role in gene expression, calcium release, cell cycle progression, DNA repair, and
      cell proliferation. Many strategies exploring the potential of interfering with
      NAD+ metabolism to sensitize cancer cells to achieve anticancer benefits are
      highly promising, and are being pursued. CRITICAL ISSUES: With the multifaceted
      roles of NAD+ in cancer, it is important to understand how cellular processes are
      reliant on NAD+. This review summarizes how NAD+ metabolism regulates various
      pathophysiological processes in cancer, and how this knowledge can be exploited
      to devise effective anticancer therapies in clinical settings. FUTURE DIRECTIONS:
      In line with the redundant pathways that facilitate NAD+ metabolism, further
      studies should comprehensively understand the roles of the various NAD+
      synthesizing as well as NAD+-utilizing biomolecules to understand its true
      potential in cancer treatment. Antioxid. Redox Signal. 00, 000-000.

PMID- 29334762
TI  - Altered Redox State Modulates Endothelial KCa2.3 and KCa3.1 Levels in Normal
      Pregnancy and Preeclampsia.
AB  - AIMS: Altered redox state has been related to the development of normal pregnancy
      (NP) and preeclampsia (PE). Endothelial KCa2.3 and KCa3.1 (KCas) play an
      important role in vasodilation, and KCas levels are affected by oxidative stress.
      We investigated the mechanisms of oxidative stress-mediated KCas expression
      modulation during NP and PE. RESULTS: Human uterine microvascular endothelial
      cells were incubated in serum from normal nonpregnant women (n = 13) and women
      with NP (n = 24) or PE (n = 15), or in vascular endothelial growth factor (VEGF),
      oxidized low-density lipoprotein (ox-LDL), progesterone, or estradiol-17beta (E2)
      containing medium for 24 h. NP serum elevated H2O2 levels via reducing catalase
      and glutathione peroxidase 1 levels, thereby enhancing KCas levels via a
      H2O2/fyn/extracellular signal-regulated kinase (ERK)-mediated pathway. VEGF
      enhanced H2O2 and KCas levels and KCa3.1 currents. KCas were upregulated and KCas
      activation-induced endothelium-dependent relaxation (EDR) was augmented in
      vessels from pregnant mice and rats. Whereas PE serum, ox-LDL, progesterone, or
      soluble fms-like tyrosine kinase 1 (sFlt-1) elevated superoxide levels via
      elevating NADPH oxidase 2 (NOX2) and NOX4 levels and reducing superoxide
      dismutase (SOD) 1 levels, thereby downregulating KCas. sFlt-1 inhibited EDR. PE
      serum- or progesterone-induced alterations in levels of KCas were reversed by
      polyethylene glycol-SOD, NOX inhibition, or E2. Innovation and Conclusions: This
      is the first study of how endothelial KCas levels are modulated during NP and PE.
      KCas were upregulated by soluble serum factors such as VEGF via H2O2 generation
      in NP, and were downregulated by serum factors such as progesterone and ox-LDL
      via superoxide generation in PE, which may contribute to hemodynamic adaptations
      in NP or to the development of PE. Antioxid. Redox Signal. 00, 000-000.

PMID- 29334763
TI  - Long Noncoding RNA LINC01619 Regulates MicroRNA-27a/Forkhead Box Protein O1 and
      Endoplasmic Reticulum Stress-Mediated Podocyte Injury in Diabetic Nephropathy.
AB  - AIMS: Altered activities of long noncoding RNAs (lncRNAs) have been implicated in
      the regulation of microRNAs. microRNA-27a (miR-27a) upregulation has been shown
      to induce endoplasmic reticulum (ER) stress podocyte injury in diabetic
      nephropathy (DN). Herein, we aim to interrogate the mutually regulated network of
      miR-27a with long intergenic noncoding RNA 1619 (LINC01619) and the target gene.
      RESULTS: LINC01619 downregulation was found in human DN renal biopsy tissues and
      contributed to proteinuria and diminished renal function. LINC01619 was expressed
      in podocyte cytoplasm and involved in ER stress signaling pathway. LINC01619
      exerted biological function by serving as a "sponge" for miR-27a, which
      negatively targeted forkhead box protein O1 (FOXO1) and activated ER stress. In
      diabetic rats and high-glucose cultured podocytes, LINC01619 triggered oxidative
      stress and podocyte injuries as demonstrated by increased apoptosis, diffuse
      podocyte foot process effacement, and decreased renal function. Innovation and
      Conclusion: This study demonstrates that LINC01619 functions as a competing
      endogenous RNA and regulates miR-27a/FOXO1-mediated ER stress and podocyte injury
      in DN. Antioxid. Redox Signal. 29, 355-376.

PMID- 29334764
TI  - Development of Gene Therapeutics for Head and Neck Cancer in China: From Bench to
      Bedside.
AB  - Head and neck cancer represents the seventh most common cancer worldwide.
      Although multidisciplinary sequential treatments have been used, there is still
      an urgent need for new treatment approaches that can effectively improve the
      outcomes of patients with advanced stages of head and neck cancer. Gene therapy
      is a rapidly evolving field in cancer therapy that has been shown to improve the
      efficacy of antitumor treatment. China is at the forefront in clinical trials and
      practice of gene therapy. Chinese researchers have mainly focused on gene
      therapeutics based on oncolytic virus and recombinant adenovirus expressing p53,
      antiangiogenesis factor or herpes simplex virus-thymidine kinase. Currently, two
      gene therapy drugs, Gendicine and Oncorine, have been marketed in China, and a
      number of upcoming gene therapy agents are under development for the treatment of
      head and neck cancer. Most gene therapy agents have demonstrated excellent
      tolerance. However, the therapeutic effects need further improvement. With
      current innovations in tumor biology and knowledge, gene therapy has great
      potential as a safe and effective anticancer treatment. In recent years, new gene
      therapy agents with promising effects have been incorporated into clinical trials
      in China. Thus, gene therapy may become an important part of anticancer therapy
      and is expected to improve the therapeutic effect of head and neck cancers in the
      near future.

PMID- 29334765
TI  - Examining Use of Mobile Phones for Sleep Tracking Among a National Sample in the
      USA.
AB  - Mobile technology has been designed to serve a number of functions relating to
      health, but we know little about individuals who use these tools to track sleep.
      This study utilized data from a cross-sectional, geographically diverse survey of
      adults in the USA (N = 934). Among the sample, 28.2% (n = 263) report current use
      of a mobile phone for sleep tracking. Income and gender were significant
      correlates of sleep tracking (p < 0.05). Compared to a poor diet, a reported
      "excellent" diet was associated with sleep tracking (p < 0.05). Interestingly,
      compared to individuals who never smoke, report of smoking "everyday" was
      associated with sleep tracking (p < 0.05). Finally, individuals who reported
      current use of their mobile device for other health functions (e.g., chat with
      their doctor or log symptoms) were more likely to report sleep tracking on their
      mobile device (p < 0.05). Results appear to suggest sleep tracking is common
      among individuals with good general health.

PMID- 29334766
TI  - AJMQ Newsletter: Register Now! Medical Quality 2018: Improving Population Health
      Through Health Equity and Patient Advocacy.

PMID- 29334767
TI  - A novel adaptive algorithm for 3D finite element analysis to model extracortical
      bone growth.
AB  - Extracortical bone growth with osseointegration of bone onto the shaft of massive
      bone tumour implants is an important clinical outcome for long-term implant
      survival. A new computational algorithm combining geometrical shape changes and
      bone adaptation in 3D Finite Element simulations has been developed, using a soft
      tissue envelope mesh, a novel concept of osteoconnectivity, and bone remodelling
      theory. The effects of varying the initial tissue density, spatial influence
      function and time step were investigated. The methodology demonstrated good
      correspondence to radiological results for a segmental prosthesis.

PMID- 29334768
TI  - Angular and metric analysis of the neural structures in the cerebellopontine
      angle.
AB  - INTRODUCTION: The cerebellopontine angle (CPA) is a subarachnoid space in the
      lateral aspect of the posterior fossa. In this study, we propose a complementary
      analysis of the CPA from the cerebellopontine fissure. METHODS: We studied 50
      hemi-cerebelli in the laboratory of neuroanatomy and included a description of
      the CPA anatomy from the cerebellopontine fissure and its relationship with the
      flocculus and the 5th, 6th, 7th, and 8th cranial nerves (CN) origins. RESULTS:
      The average distance from the 5th CN to the mid-line (ML) was 19.2 mm, 6th CN to
      ML was 4.4 mm, 7-8 complex to ML was 15.8 mm, flocculus to ML was 20.5 mm, and
      flocculus to 5th CN was 11.5 mm, additionally, and the diameter of the flocculus
      was 9.0 mm. The angle between the vertex in the flocculus and the V CN and the
      medullary-pontine line was 64.8 degrees. DISCUSSION: The most common access to
      the CPA is through the retrosigmoid-suboccipital region and this approach can be
      done with the help of an endoscope. The anatomy of origins of neural structures
      tends to be preserved in cases of CPA lesions. CONCLUSION: Knowledge of the
      average distances between the neural structures in the cerebellar-pontine fissure
      and the angular relationships between these structures facilitates the use of
      surgical approaches such as microsurgery and endoscopy.

PMID- 29334769
TI  - Topographic Analysis of the Distal Femoral Condyle Articular Cartilage Surface:
      Adequacy of the Graft from Opposite Condyles of the Same or Different Size for
      the Osteochondral Allograft Transplantation.
AB  - Objective To analyze the topography of the opposite condyle to treat focal
      femoral condyle articular defects with an osteochondral allograft (OCA). Design
      Three groups were created: Group 1, same condyle with same width; Group 2,
      opposite condyle with same width; Group 3, opposite condyle with different width.
      Computed tomography (CT) of 22 cadaveric femoral hemi-condyles was used to create
      3-dimensional CT models that were exported into point-cloud models. Three zones
      of the donor condyle (anterior, middle, and posterior) were quantified. Four
      defect sizes were created (15, 18, 23, 25 mm) at the weight-bearing region. The
      defect was moved throughout each donor condyle zone and the least distance was
      calculated, defined as the shortest distance between the defect and the donor
      condyle. Results The mean least distance increased with larger defect size in all
      groups, yet there was a less than 0.2 mm difference in the least distance among
      defect sizes. The 15, 18, and 23 mm defect models in Group 1 exhibited greater
      least distances at the anterior than middle and posterior zones. The 15 mm defect
      model exhibited greater least distance at the anterior zone than posterior zone
      in Group 3. However, there was a less than 0.05 mm difference in the mean least
      distance between zones. There was no significant difference in the least distance
      between groups. Conclusion OCAs from opposite condyles yield similar topographic
      matching to OCAs from the same condyles, suggesting that opposite condyles can be
      utilized. Clinical correlation and outcomes are necessary.

PMID- 29334770
TI  - Student Perceptions of Collaboration Skills in an Interprofessional Context:
      Development and Initial Validation of the Self-Assessed Collaboration Skills
      Instrument.
AB  - An integral component of interprofessional education (IPE) is the development of
      a collaboration-ready health-care workforce. While collaboration is a fundamental
      element of IPE, there is no existing measure of collaboration skills that is not
      context specific. This article describes the development and initial validation
      of the Self-Assessed Collaboration Skills (SACS) measure. Items were initially
      drawn from the Collaboration Skills Assessment Tool rubric, an educational
      assessment tool. The SACS measure was piloted in a sample of students in an
      introductory IPE course. Following scale revision, the SACS was piloted a second
      time in a sample of students in an IPE health systems course and then validated
      in a sample of students in an introductory IPE course. Exploratory factor
      analysis was used to assess scale factor structure in Pilots 1 and 2 and
      confirmatory factor analysis to confirm factor structure in the validation
      sample. Convergent and discriminant validity were also assessed. The final SACS
      measure is an 11-item scale consisting of three dimensions of collaboration:
      information sharing, learning, and team support. The SACS measure demonstrates
      high internal consistency and both convergent and discriminant validity as a
      measure of collaboration. The SACS can be implemented in any setting for
      assessing collaboration in clinical and nonclinical contexts.

PMID- 29334772
TI  - Spontaneous regression of a large skull base meningioma: case report.
AB  - We present the case of a 58 year old lady with a large middle cranial fossa
      meningioma (5 cm * 4 cm in maximal dimensions) which has considerably regressed
      without any treatment during seven years of follow up. While the tumour had
      remained radiologically static for the first three years, scans from year five
      post-diagnosis onwards have shown shrinkage of the meningioma from a calculated
      volume of 36 cm3 to 11.2 cm3. There has been no intratumoral haemorrhage or
      infarction and no medication or exogenous hormonal effect that could account for
      this effect. We reviewed the literature and report that this is only the second
      ever case of spontaneous regression of meningioma.

PMID- 29334771
TI  - Development of Anti-Human Mesothelin-Targeted Chimeric Antigen Receptor Messenger
      RNA-Transfected Peripheral Blood Lymphocytes for Ovarian Cancer Therapy.
AB  - CD19-targeted chimeric antigen receptor (CAR) engineered T/natural killer (NK)
      cell therapies can result in durable clinical responses in B-cell malignancies.
      However, CAR-based immunotherapies have been much less successful in solid
      cancers, in part due to "on-target off-tumor" toxicity related to expression of
      target tumor antigens on normal tissue. Based on preliminary observations of
      safety and clinical activity in proof-of-concept clinical trials, tumor antigen
      specific messenger RNA (mRNA) CAR transfection into selected, activated, and
      expanded T/NK cells may permit prospective control of "on-target off-tumor"
      toxicity. To develop a commercial product for solid tumors, mesothelin was
      selected as an antigen target based on its association with poor prognosis and
      overexpression in multiple solid cancers. It was hypothesized that selecting,
      activating, and expanding cells ex vivo prior to mRNA CAR transfection would not
      be necessary, thus simplifying the complexity and cost of manufacturing. Now, the
      development of anti-human mesothelin mRNA CAR transfected peripheral blood
      lymphocytes (CARMA-hMeso) is reported, demonstrating the manufacture and
      cryopreservation of multiple cell aliquots for repeat administrations from a
      single human leukapheresis. A rapid, automated, closed system for cGMP-compliant
      transfection of mRNA CAR in up to 20 * 109 peripheral blood lymphocytes was
      developed. Here we show that CARMA-hMeso cells recognize and lyse tumor cells in
      a mesothelin-specific manner. Expression of CAR was detectable over approximately
      7 days in vitro, with a progressive decline of CAR expression that appears to
      correlate with in vitro cell expansion. In a murine ovarian cancer model, a
      single intraperitoneal injection of CARMA-hMeso resulted in the dose-dependent
      inhibition of tumor growth and improved survival of mice. Furthermore, repeat
      weekly intraperitoneal administrations of the optimal CARMA-hMeso dose further
      prolonged disease control and survival. No significant off-target toxicities were
      observed. These data support further investigation of CARMA-hMeso as a potential
      treatment for ovarian cancer and other mesothelin-expressing cancers.

PMID- 29334773
TI  - MACF1 Overexpression by Transfecting the 21 kbp Large Plasmid PEGFP-C1A-ACF7
      Promotes Osteoblast Differentiation and Bone Formation.
AB  - Microtubule actin crosslinking factor 1 (MACF1) is a large spectraplakin protein
      known to have crucial roles in regulating cytoskeletal dynamics, cell migration,
      growth, and differentiation. However, its role and action mechanism in bone
      remain unclear. The present study investigated optimal conditions for effective
      transfection of the large plasmid PEGFP-C1A-ACF7 (~21 kbp) containing full-length
      human MACF1 cDNA, as well as the potential role of MACF1 in bone formation. To
      enhance MACF1 expression, the plasmid was transfected into osteogenic cells by
      electroporation in vitro and into mouse calvaria with nanoparticles. Then,
      transfection efficiency, osteogenic marker expression, calvarial thickness, and
      bone formation were analyzed. Notably, MACF1 overexpression triggered a drastic
      increase in osteogenic gene expression, alkaline phosphatase activity, and matrix
      mineralization in vitro. Mouse calvarial thickness, mineral apposition rate, and
      osteogenic marker protein expression were significantly enhanced by local
      transfection. In addition, MACF1 overexpression promoted beta-catenin expression
      and signaling. In conclusion, MACF1 overexpression by transfecting the large
      plasmid containing full-length MACF1 cDNA promotes osteoblast differentiation and
      bone formation via beta-catenin signaling. Current data will provide useful
      experimental parameters for the transfection of large plasmids and a novel
      strategy based on promoting bone formation for prevention and therapy of bone
      disorders.

PMID- 29334774
TI  - Three column osteotomy for adult spine deformity: comparison of outcomes and
      complications between kyphosis and kyphoscoliosis.
AB  - BACKGROUND: To compare the surgical outcomes and complications between kyphosis
      and kyphoscoliosis when using three-column osteotomies. METHODS: Adult spine
      deformity (ASD) patients with three column osteotomies from March 2005 to
      December 2014 in our center were retrospectively reviewed. Pre- and postoperative
      standing postero-anterior and lateral radiographs of the entire spine were
      obtained. Scoliosis Research Society-22 questionnaire [SRS-22] and Oswestry
      Disability Index [ODI] were administered preoperatively, postoperatively (surveys
      within 2 months after surgery), and at final follow-up. Patients were assigned to
      one of two groups according to pre-operative coronal curve magnitude: (1) if
      coronal curve <10 degrees , patients were assigned to kyphosis group (K group);
      (2) if coronal curve >40 degrees , patients were assigned to kyphoscoliosis group
      (S group). RESULTS: 33 ASD patients were assigned to the kyphosis group (K
      group), of which 26 received PSO (pedicle subtraction osteotomy) and 7 VCR
      (vertebral column resection). 76 patients were assigned to kyphoscoliosis group
      (S group), of which 50 received PSO and 26 VCR. Patients in the K group were
      significantly older than in the S group (42.8 vs. 33.7 years, p < .05).
      Significantly longer OT (operation time) and more EBL (estimated blood loss) were
      observed in the S group as compared to K group (OT: 282 vs. 205 min, p < .05;
      EBL: 1827 vs. 1214ml, p < .05). No significant difference was noted for number of
      fusion levels between the groups (12.4 vs. 12.7, p > .05). Pre-operative
      radiographic parameters demonstrated no difference of GK (global kyphosis) and
      SVA (sagittal vertical axis) between the two groups (GK: 74.7 degrees  vs 76.2
      degrees , p > .05; SVA:53.2 vs. 55.7mm, p > .05). K group had larger KF than S
      group (26% vs. 15%, p < .05). Overall complication rate was higher in S group
      than in K group (30.3% vs. 18.2%, p < .05). No difference of neurological
      complication rates between the two groups (9.1% vs. 10.5%, p > .05). CONCLUSIONS:
      Kyphoscoliosis group had less KF, GK correction and more OT, EBL and surgical
      complications when receiving three column osteotomies.

PMID- 29334775
TI  - Resistance to Acetaminophen Interference in a Novel Continuous Glucose Monitoring
      System.
AB  - Acetaminophen (APAP) can cause erroneously high readings in real-time continuous
      glucose monitoring (rtCGM) systems. APAP-associated bias in an investigational
      rtCGM system (G6) was evaluated by taking the difference in glucose measurements
      between rtCGM and YSI from 1 hour before to 6 hours after a 1-g oral APAP dose in
      66 subjects with type 1 or type 2 diabetes. The interference effect was defined
      as the average post-dose (30-90 minutes) bias minus the average baseline bias for
      each subject. The clinically meaningful interference effect was defined as 10
      mg/dL. The G6 system's overall mean (+/-SD) interference effect was 3.1 +/- 4.8
      mg/dL (one-sided upper 95% CI = 4.1 mg/dL), significantly lower than 10 mg/dL.
      The G6 system's resistance to APAP interference should provide reassurance to
      those using the drug.

PMID- 29334776
TI  - Multiple intracranial aneurysms in a patient with type I Gaucher disease: a case
      report and literature review.
AB  - Multiple intracranial aneurysms (IAs) have never been reported in a patient with
      Gaucher disease (GD). A 69-year-old-female with type I GD presented with a left
      sixth nerve palsy due to a large posterior inferior cerebellar artery (PICA)
      aneurysm. Cerebral angiography demonstrated fifteen unruptured IAs (UIAs).

PMID- 29334777
TI  - Endovascular implantation of 125I seed combined with transcatheter arterial
      chemoembolization for unresectable hepatocellular carcinoma.
AB  - AIM: The purpose of this study was to evaluate the efficacy and safety of the
      endovascular implantation of 125I seed under ultrasound and x-ray guidance
      combined with transcatheter arterial chemoembolization (TACE) for hepatocellular
      carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT). PATIENTS &
      METHODS: The study included 134 pathologically proven or clinically confirmed
      primary HCC patients with PVTT in our hospital from January 2013 to June 2015.
      RESULTS & CONCLUSION: Compared with the TACE treatment alone, the combination
      therapy of 125I seed implantation with TACE significantly prolonged the median
      survival time and improved the 6-, 12- and 18-month survival rates for HCC
      patients with PVTT. In addition, the type III PVTT and tumor size were
      independent predictors for poor prognosis of HCC patients with PVTT.

PMID- 29334778
TI  - Fluid Dynamic Analysis of Hand-Pump Infuser and UROMAT Endoscopic Automatic
      System for Irrigation Through a Flexible Ureteroscope.
AB  - INTRODUCTION: To evaluate the flow characteristics produced by a manual and
      automated-pump irrigation system connected to a flexible ureteroscope. MATERIALS
      AND METHODS: An in vitro analysis of a manual hand-pump infuser (HP) and the
      UROMAT Endoscopic Automatic System for Irrigation(r) (E.A.S.I.) pump was
      performed. Standard irrigation tubing was used to connect a three-way valve to a
      flexible ureteroscope, the irrigation system, and a digital manometer. Flow rate
      and irrigation pressure measurements were recorded over a 15-minute period using
      pressure settings of 150 and 200 mm Hg for both irrigation pump systems. Once the
      HP was inflated to the initial pressure, it was not reinflated over the course of
      the trial. Data were collected with the working channel unoccupied and with
      placement of a 200 MUm (0.6F) holmium laser fiber, 1.7F nitinol stone retrieval
      basket, or 2.67F guidewire. RESULTS: The difference in pressure measured at the
      site of inflow of irrigation to the ureteroscope was significantly greater using
      the HP compared to the E.A.S.I. pump at pressure settings of 150 mm Hg with and
      without the use of ureteroscopic instrumentation (p < 0.001), and at 200 mm Hg
      with instrumentation in the working channel (p < 0.01). There was no significant
      difference in the flow rate of irrigation through the open-channel ureteroscope
      over the course of 5 minutes between the two pump systems. CONCLUSION: The flow
      rates of irrigation produced by the HP and the E.A.S.I. pump are similar at
      pressures of 150 and 200 mm Hg irrespective of the occupancy of a ureteroscope's
      working channel during the first 5-minutes of irrigation. Irrigation pressure at
      the entry site of the ureteroscope is subject to significant variability with use
      of the HP compared to the E.A.S.I. pump irrigation system.

PMID- 29334779
TI  - Extra-articular tenosynovial giant cell tumor of diffuse type in the temporal
      area with brain parenchymal invasion: a case report.
AB  - Tenosynovial giant cell tumor of diffuse type is a locally aggressive neoplasm
      that most commonly arises in the lower extremities. Herein, we report for the
      first time a case of an extra-articular tenosynovial giant cell tumor of diffuse
      type in the temporal region with brain parenchymal invasion. Imaging studies
      revealed an intracranial expansile mass in the temporal bone without involvement
      of the temporomandibular joint. The unusual location of the tumor without
      involvement of the joint and the presence of brain parenchymal invasion made this
      case challenging to diagnose.

PMID- 29334781
TI  - Correction to: Coulter et al., Real-time symptom reporting during elective
      intracranial pressure monitoring using an interactive handset.

PMID- 29334780
TI  - Rules governing the mechanism of epigenetic reprogramming memory.
AB  - AIM: Disclosing the mechanisms that regulate reprogramming memory. MATERIALS &
      METHODS: We established computational procedure to find DNA methylation somatic
      memory sites (SMSs) at single CpGs and integrated them with genomics,
      epigenomics, transcriptomics and imprinting information. RESULTS & CONCLUSION:
      Reprogramming memory persists at late passages in low methylated regions.
      Contrarily to hypomethylated, hypermethylated SMSs occur at evolutionary
      conserved sites overlapping active transcription loci in dynamic chromatin
      regions. The epigenetic-memory molecular origin is the expression of source-cell
      transcription factors protecting hypomethylated SMSs in euchromatin from de novo
      methylation, keeping source-cell lineage-specific loci in induced pluripotent
      stem (iPS) cells incompletely silenced. Sites in lineage-specific genes of
      different-from-those-of-the-source-cell lineages remain hypermethylated in
      heterochromatin regions becoming permanently silenced. SMSs cause differential
      expression between iPS cells and embryonic stem cells through two mechanisms:
      'epigenetic/expression memory rule', the DNA unreprogramming methylation status
      coupled with chromatin states induces differentially expressed genes. 'Imprinting
      control', the change of DNA methylation status in imprinting control regions
      induces differential expression of imprinted genes.

PMID- 29334782
TI  - Outcomes of Bilateral vs Unilateral Ankle Arthrodesis.
AB  - BACKGROUND: While ankle arthrodesis is a common treatment for severe ankle
      osteoarthritis, performing bilateral ankle arthrodesis is controversial because
      of associated problems, such as severe gait abnormality and bilateral loss of
      talocrural joint motion. Furthermore, few reports exist regarding the detailed
      outcomes of bilateral ankle arthrodesis. Therefore, we aimed to compare the
      outcomes of bilateral ankle arthrodesis with those of unilateral ankle
      arthrodesis, using both subjective and objective assessments. METHODS: The data
      from 20 patients (10 each in the bilateral and unilateral groups), who underwent
      arthrodesis between 2005 and 2015, were retrospectively reviewed. The minimum
      follow-up duration was 2 years. Radiographic outcomes were assessed using
      radiographs and computed tomography. Clinical outcomes were assessed using the
      Japanese Society for Surgery of the Foot (JSSF) scale and the Self-Administered
      Foot Evaluation Questionnaire (SAFE-Q). RESULTS: With the numbers available, no
      significant group differences were observed for any of the patient
      characteristics or postoperative range of motion. Mean JSSF scale scores
      significantly improved in both groups ( P < .001); however, scores on the SAFE-Q
      subscale for "social functioning" were significantly lower in the bilateral group
      compared to the unilateral group ( P = .049). CONCLUSIONS: Within the limitations
      of the current study design, bilateral ankle arthrodesis did not appear to be
      inferior to unilateral ankle arthrodesis, with the possible exception of social
      functioning ability. Thus, bilateral ankle arthrodesis can be considered a viable
      treatment option. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

PMID- 29334783
TI  - Frailty: A global measure of the multisystem impact of COPD.
AB  - Chronic obstructive pulmonary disease (COPD) is a multisystem disease that
      resembles the accumulation of multiple impairments seen in aging. A comprehensive
      geriatric assessment (CGA) captures multisystem deficits, from which a frailty
      index (FI) can be derived. We hypothesized that patients with COPD would be
      frailer than a comparator group free from respiratory disease. In this cross
      sectional analysis, the CGA questionnaire was completed and used to derive an FI
      in 520 patients diagnosed with COPD and 150 comparators. All subjects were
      assessed for lung function, body composition, 6-minute walking distance (6MWD),
      and handgrip strength. Patients completed validated questionnaires on health
      related quality of life and respiratory symptoms. Patients and comparators were
      similar in age, gender, and body mass index, but patients had a greater mean +/-
      SD FI 0.16 +/- 0.08 than comparators 0.05 +/- 0.03. In patients, a stepwise
      linear regression 6MWD ( beta = -0.43), number of comorbidities ( beta = -0.38),
      handgrip ( beta = -0.11), and number of exacerbations ( beta = 0.11) were
      predictors of frailty (all p < 0.01). This large study suggests patients with
      COPD are frailer than comparators. The FI derived from the CGA captures the
      deterioration of multiple systems in COPD and provides an overview of
      impairments, which may identify individuals at increased risk of morbidity and
      mortality in COPD.

PMID- 29334784
TI  - Unilateral lag screw fixation of isolated non-union atlas lateral mass fracture:
      a new technical note.
AB  - We describe a novel and new technique of posterior unilateral lag screw fixation
      of non-union atlas lateral mass fracture. A 46-year-old man presented with
      cervical pain and tenderness after a vehicle turn over accident and he was
      diagnosed to have left atlas lateral mass fracture. He was initially treated by
      immobilization using Minerva orthosis. About 2 months later, he developed severe
      neck pain and limitation of motion and thus he was scheduled for operation due to
      non-union atlas lateral mass fracture. A 28 mm lag screw was inserted under
      anterior-posterior and lateral fluoroscopic views. The entrance point was at the
      dorsal aspect of left atlas posterior arc at its junction to the lateral mass,
      and by using the trajectory of 10 degrees medial and 22 degrees cephalad fracture
      reduction was achieved. Unilateral lag screw fixation of atlas fractures is an
      appropriate, safe and effective surgical technique for the management of
      unilateral atlas fractures.

PMID- 29334785
TI  - The use of combination immunotherapies as front-line therapy for non-small-cell
      lung cancer.

PMID- 29334786
TI  - Acute-on-chronic liver failure in chronic hepatitis B: an update.
AB  - INTRODUCTION: Acute-on-chronic liver failure is a common pattern of end-stage
      liver disease in clinical practice and occurs frequently in patients with chronic
      hepatitis B or HBV-related cirrhosis. New progress in recent years leads to a
      better understanding of this disease. Areas covered: This review updates the
      current comprehensive knowledge about HBV-ACLF from epidemiological studies,
      experimental studies, and clinical studies and provide new insights into the
      definition, diagnostic criteria, epidemiology, nature history, pathogenesis,
      treatment and prognostication of HBV-ACLF. Expert commentary: Patients with
      chronic hepatitis B or HBV-related cirrhosis are at risk of developing acute-on
      chronic liver failure, with multi-organ failure and high short-term mortality.
      The precipitating events can be intra-hepatic or extra-hepatic and the underlying
      chronic liver injury can be cirrhotic or non-cirrhotic. Host and viral factors
      contribute to the susceptibility of developing HBV-ACLF. Systemic inflammation is
      the driver of HBV-ACLF, which can be attributed to non-sterile and sterile
      factors. Liver transplantation is the definitive treatment for HBV-ACLF. Cell
      therapy is a promising alternative to LT, but requires validation and still has
      concern of long-term safety. Other medical therapies, such as nucleoside
      analogue, artificial liver supporting and glucocorticoid may improve survival in
      a specific subgroup. New scoring systems improve the accuracy of prognostication
      in HBV-ACLF, which is critical for early identification of candidates for LT.

PMID- 29334787
TI  - Analysis of endocannabinoid receptors and enzymes in the post-mortem motor cortex
      and spinal cord of amyotrophic lateral sclerosis patients.
AB  - OBJECTIVE: We have investigated the endocannabinoid system in the motor cortex of
      motor neuron disease (MND) patients. METHODS: Post-mortem samples from MND
      patients and controls were used for immunostaining and/or Western blotting
      analysis of endocannabinoid elements. RESULTS: We did not find any evidence of
      neuronal losses in the motor cortex of MND patients, but elevations in glial
      markers Iba-1 and GFAP were evident. We found no changes in FAAH and MAGL enzymes
      and in the CB1 receptor, which correlated with the lack of cortical neuron death.
      By contrast, the Western blotting analysis of CB2 receptors proved an increase in
      the motor cortex corroborated by immunostaining, correlating with the elevated
      gliosis in these patients. Double-labeling analyses revealed that this elevated
      CB2 receptor immunostaining was located in GFAP-labelled astroglial cells.
      However, we also found CB2 receptor labeling in cortical neurons confirmed with
      double immunofluorescence with the neuronal marker MAP-2. This was also found in
      the spinal cord, using double-labeling with the spinal motor neuron marker
      choline-acetyl transferase. This happened in both patients and controls, despite
      these neurons experienced an important degeneration in patients reflected in
      reduced Nissl staining, TDP-43 immunostaining and CB1 receptor levels measured by
      Western blotting. CONCLUSION: We have confirmed that CB2 receptors are elevated
      in the motor cortex of MND patients associated with the reactive gliosis. This
      phenomenon is previous to neuronal losses. We also found CB2 receptors in
      cortical and spinal motor neurons. These observations support that targeting this
      receptor may serve for developing neuroprotective therapies in MNDs.

PMID- 29334788
TI  - Latissimus Dorsi Flap in Breast Reconstruction: Recent Innovations in the
      Workhorse Flap.
AB  - BACKGROUND: Surgeons employ the latissimus dorsi flap (LDF) for reconstruction of
      a large variety of breast cancer surgery defects, including quadrantectomy,
      lumpectomy, modified radical mastectomy, and others. The LDF may be used in
      delayed or immediate reconstruction, in combination with tissue expanders for a
      staged reconstruction, with implant-based immediate reconstruction, or alone as
      an autogenous flap. METHODS: The authors discuss the historical uses and more
      recent developments in the LDF. More recent advancements, including the
      "scarless" approach and augmentation with the thoracodorsal artery perforator
      flap, are discussed. RESULTS: The LDF is a reliable means for soft tissue
      coverage providing form and function during breast reconstruction with acceptable
      perioperative and long-term morbidities. CONCLUSIONS: When there is a paucity of
      tissue, the LDF can provide tissue volume in autologous reconstruction, as well
      as a reliable vascular pedicle for implant-based reconstruction as in the setting
      of irradiated tissue.

PMID- 29334789
TI  - Circular RNA expression in ovarian endometriosis.
AB  - AIM: Circular RNAs (circRNAs) with miRNA response elements (MREs) could function
      as competing endogenous RNA (ceRNA) in regulating gene expression. This study was
      carried out to identify the expression profile and role of circRNAs in
      endometriosis. MATERIALS & METHODS: Microarray assay was performed in four paired
      ovarian endometriomas and eutopic endometrium, followed by quantitative real-time
      RT-PCR in 24 paired samples. Bioinformatical algorithms were used to predict
      MREs, as well as ceRNA and KEGG pathway analysis. RESULTS: We identified 262
      upregulated and 291 downregulated circRNAs, binding with 1225 MREs. The ceRNA
      network included 122 miRNAs and 137 mRNAs, which are involed in nine pathways.
      CONCLUSION: CircRNAs are differentially expressed in endometriosis, which might
      be related with pathogenesis of endometriosis.

PMID- 29334790
TI  - Cognitive work hardening for return to work following depression: An intervention
      study: Le reentrainement cognitif au travail pour favoriser le retour au travail
      a la suite d'une depression : etude d'intervention.
AB  - BACKGROUND: Work absences due to depression are prevalent; however, few
      interventions exist to address the return-to-work challenges following a
      depressive episode. PURPOSE: This mixed-methods study aimed to (a) evaluate the
      effectiveness of cognitive work hardening in preparing people with depression to
      return to work and (b) identify key elements of the intervention. METHOD: A
      single group ( n = 21) pretest-posttest study design was used incorporating self
      report measures (Work Ability Index, Multidimensional Assessment of Fatigue, Beck
      Depression Inventory II) with interviews at intervention completion and at 3
      month follow-up. Descriptive statistics, paired-samples t test, and content
      analysis were used to analyze the data. FINDINGS: Work ability, fatigue, and
      depression severity significantly improved postintervention. Participants
      identified structure, work simulations, realism of simulated work environment,
      support, and education as key intervention elements. IMPLICATIONS: Findings
      underscore an occupationally focused return-to-work intervention for people
      recovering from depression with potential for wider adoption and future research.

PMID- 29334792
TI  - Mothers' opinions on being asked about exposure to intimate partner violence in
      child healthcare centres in Sweden.
AB  - Intimate partner violence (IPV) constitutes a hidden health risk for exposed
      mothers and children. In Sweden, screening for IPV in healthcare has only been
      routine during pregnancy, despite an increase in IPV following childbirth. The
      arguments against routine questions postpartum have concerned a lack of evidence
      of beneficial effects as well as fear of stigmatizing women or placing abused
      women at further risk. Increased understanding of women's attitudes to routine
      questions may allay these fears. In this study, 198 mothers in 12 child
      healthcare centres (CHCs) filled in a short questionnaire about their exposure
      and received information on IPV at a regular baby check-up visit. The mothers'
      lifetime prevalence of exposure to IPV was 16%. One hundred and twenty-eight
      mothers participated in a telephone interview, giving their opinion on the
      screening experience. The intervention was well-received by most of the mothers
      who reported that questions and information on IPV are essential for parents,
      considering the health risks for children, and that the CHC is a natural arena
      for this. Necessary prerequisites were that questioning be routine to avoid
      stigmatizing and be offered in privacy without the partner being present.

PMID- 29334791
TI  - Application of Fluorescence-Guided Surgery to Subsurface Cancers Requiring Wide
      Local Excision: Literature Review and Novel Developments Toward Indirect
      Visualization.
AB  - The excision of tumors by wide local excision is challenging because the mass
      must be removed entirely without ever viewing it directly. Positive margin rates
      in sarcoma resection remain in the range of 20% to 35% and are associated with
      increased recurrence and decreased survival. Fluorescence-guided surgery (FGS)
      may improve surgical accuracy and has been utilized in other surgical
      specialties. ABY-029, an anti-epidermal growth factor receptor Affibody molecule
      covalently bound to the near-infrared fluorophore IRDye 800CW, is an excellent
      candidate for future FGS applications in sarcoma resection; however, conventional
      methods with direct surface tumor visualization are not immediately applicable. A
      novel technique involving imaging through a margin of normal tissue is needed. We
      review the past and present applications of FGS and present a novel concept of
      indirect FGS for visualizing tumor through a margin of normal tissue and aiding
      in excising the entire lesion as a single, complete mass with tumor-free margins.

PMID- 29334794
TI  - A look at the progress of treating pancreatic cancer over the past 20 years.
AB  - INTRODUCTION: Pancreatic cancer is known to be the deadliest of all common
      cancers. Despite all efforts in pancreatic cancer treatment, the five-year
      survival rates at diagnosis over the past 20 years have only increased from 5% to
      8%. Assuming that pancreatic cancer is going to become the second most frequent
      cause of cancer related death in the next 20 years, we are all encouraged to
      treat patients in clinical trials to gain improvements in this devastating
      disease. Areas covered: This review will provide a summary of pancreatic cancer
      treatment over the last 20 years, starting with the pivotal study in 1997 which
      showed the superiority of gemcitabine over 5-FU in advanced pancreatic cancer and
      is marked as the beginning of a new era in pancreatic cancer treatment. This
      review will also focus on improvements in different areas of treatment, including
      pancreatic surgery, adjuvant treatment, neoadjuvant therapy and palliative
      therapy. Expert commentary: The treatment of pancreatic cancer has changed
      substantially in the last 20 years compared to almost no improvements in the
      decades before. This provides hope that more effective treatment options will
      become available in the near future. Particularly, new concepts such as
      neoadjuvant therapy in resectable and borderline-resectable tumors may
      potentially shift treatment strategies.

PMID- 29334793
TI  - Controlled synthesis and size effects of multifunctional mesoporous silica
      nanosystem for precise cancer therapy.
AB  - Nanomaterials-based drug delivery systems display potent applications in cancer
      therapy, owing to the enhanced permeability and retention effect and diversified
      chemical modification. In this study, we have tailored and synthesized different
      sized mesoporous silica nanoparticles (MSNs) through reactant control to
      investigate the relevancy of nanoparticle size toward anticancer efficacy and
      suppressing cancer multidrug resistance. The different sized MSNs loaded with
      anticancer ruthenium complex (RuPOP) and conjugated with folate acid (FA) to
      enhance the selectivity between cancer and normal cells. The nanosystem (Ru@MSNs)
      can specifically recognize HepG2 hepatocellular carcinoma cells, thus enhance
      accumulation and selective cellular uptake. The smaller sized (20 nm) Ru@MSNs
      exhibit higher anticancer activity against HepG2 cells, while the larger sized
      (80 nm) Ru@MSNs exhibit higher inhibitory effect against DOX-resistant
      hepatocellular carcinoma cells (R-HepG2). Moreover, Ru@MSNs induced ROS
      overproduction in cancer cells, leading to DNA damage and p53 phosphorylation,
      consequently promoting cancer cells apoptosis. Ru@MSNs (80 nm) also inhibited
      ABCB1 and ABCG2 expression in R-HepG2 cells to prevent drug efflux, thus overcome
      multidrug resistance. Ru@MSNs also inhibited tumor growth in vivo without obvious
      toxicity in major organs of tumor-bearing nude mice. Taken together, these
      results verify the size effects of MSNs nanosystem for precise cancer therapy.

PMID- 29334795
TI  - Progress in the development of histamine H3 receptor antagonists/inverse
      agonists: a patent review (2013-2017).
AB  - INTRODUCTION: Since years, ligands blocking histamine H3 receptor (H3R) activity
      (antagonists/inverse agonists) are interesting targets in the search for new
      cures for CNS disorders. Intensive works done by academic and pharmaceutical
      company researchers have led to many potent and selective H3R antagonists/inverse
      agonists. Some of them have reached to clinical trials. Areas covered: Patent
      applications from January 2013 to September 2017 and the most important topics
      connected with H3R field are analysed. Espacenet, Patentscope, Pubmed,
      GoogleScholar or Cochrane Library online databases were principially used to
      collect all the materials. Expert opinion: The research interest in histamine H3R
      field is still high although the number of patent applications has decreased
      during the past 4 years (around 20 publications). Complexity of histamine H3R
      biology e.g. many isoforms, constitutive activity, heteromerization with other
      receptors (dopamine D2, D1, adenosine A2A) and pharmacology make not easy
      realization and evaluation of therapeutic potential of anti-H3R ligands. First
      results from clinical trials have verified potential utility of histamine H3R
      antagonist/inverse agonists in some diseases. However, more studies are necessary
      for better understanding of an involvement of the histaminergic system in CNS
      related disorders and helping more ligands approach to clinical trials and the
      market. Lists of abbreviations: hAChEI - human acetylcholinesterase inhibitor;
      hBuChEI - human butyrylcholinesterase inhibitor; hMAO - human monoamine oxidase;
      MAO - monoamine oxidase.

PMID- 29334796
TI  - The systematic review of randomized controlled trials of PCSK9 antibodies
      challenges their "efficacy breakthrough" and the "lower, the better" theory.
AB  - BACKGROUND: A Cochrane review with meta-analysis showed controversial results
      about the efficacy of PCSK9 antibodies in the prevention of cardiovascular
      diseases. This review gives the opportunity to test the relationship between LDL
      C levels and cardiovascular events. METHODS: The authors analyzed the
      relationship between the calculated LDL-C lowering and the risk of all-cause
      mortality, fatal and non-fatal myocardial infarction, fatal and non-fatal stroke,
      any adverse event, cardiovascular events and cardiovascular disease mortality.
      RESULTS: No beneficial relationship was found between LDL-C lowering and
      cardiovascular events explored by meta-regression; instead, there was a trend
      toward harm. For any of the other outcomes there was no significant association
      between LDL-C lowering and risk. Furthermore, the authors calculated the efficacy
      that would be expected through the LDL-C lowering showed in the meta-analysis,
      considering widely accepted predictions. These were respected only for stroke,
      while the observed efficacy on other cardiovascular events was significantly
      lower than the expected, and no significant result was observed at all for fatal
      outcomes. A separate meta-analysis of trials recruiting familial
      hypercholesterolemia patients have showed a tendency to harm for almost all
      outcomes. CONCLUSIONS: The relationship between LDL-C lowering and cardiovascular
      events has not showed any significant association (and even a tendency toward
      harm), challenging the "lower the better" theory. A separate meta-analysis of
      trials recruiting familial hypercholesterolemia patients has showed a tendency to
      harm for all outcomes with PCSK9 antibodies. Therefore, at the moment, the data
      available from randomized trials does not clearly support the use of these
      antibodies.

PMID- 29334797
TI  - Association of functional MMP-2 gene variant with intracranial aneurysms: case
      control genetic association study and meta-analysis.
AB  - INTRODUCTION: Abnormalities in Matrix Metalloproteinase (MMP) genes, which are
      important in extracellular matrix (ECM) maintenance and therefore arterial wall
      integrity are a plausible underlying mechanism of intracranial aneurysm (IA)
      formation, growth and subsequent rupture. We investigated whether the rs243865 C
      > T SNP (single nucleotide polymorphism) within the MMP-2 gene (which influences
      gene transcription) is associated with IA compared to matched controls. MATERIALS
      AND METHODS: We conducted a case-control genetic association study, adjusted for
      known IA risk factors (smoking and hypertension), in a UK Caucasian population of
      1409 patients with intracranial aneurysms (IA), and 1290 matched controls, to
      determine the association of the rs243865 C > T functional MMP-2 gene SNP with IA
      (overall, and classified as ruptured and unruptured). We also undertook a meta
      analysis of two previous studies examining this SNP. RESULTS: The rs243865 T
      allele was associated with IA presence in univariate (OR 1.18 [95% CI 1.04-1.33],
      p = .01) and in multi-variable analyses adjusted for smoking and hypertension
      status (OR 1.16 [95% CI 1.01-1.35], p = .042). Subgroup analysis demonstrated an
      association of the rs243865 SNP with ruptured IA (OR 1.18 [95% CI 1.03-1.34] p =
      .017), but, not unruptured IA (OR 1.17 [95% CI 0.97-1.42], p = .11). CONCLUSIONS:
      Our study demonstrated an association between the functional MMP-2 rs243865
      variant and IAs. Our findings suggest a genetic role for altered extracellular
      matrix integrity in the pathogenesis of IA development and rupture.

PMID- 29334798
TI  - Vulvar vestibular effects of ospemifene: a pilot study.
AB  - The study aimed to assess the effects of ospemifene on vulvar vestibule in
      postmenopausal women with vulvar pain and dyspareunia. Fifty-five postmenopausal
      women used oral ospemifene 60 mg/d for 60 d. Symptoms of dryness, burning, and
      dyspareunia were evaluated on a 10 cm visual analog scale. Visual examination of
      the vulvar vestibule was also conducted. Patients also underwent current
      perception threshold (CPT) testing obtained from the vulvar vestibule. Fifty-five
      patients (94.6%) completed the treatment. Hot flashes were the most frequent
      adverse effects, but this led to a discontinuation of therapy in three patients
      (5.4%). After therapy, there was a statistically significant decrease from the
      baseline in the mean scores for dryness, burning, and dyspareunia and reduction
      of vestibular trophic score (baseline value of 11.2-4.2 after the therapy, p <=
      002) and cotton swab test scores (2.81 compared with 1.25, p = .001). There was a
      difference in CPT values for all nerve fibers and more consistent for C fibers (
      38% of sensitivity). These results confirm the efficacy of ospemifene on
      postmenopausal vestibular symptoms and signs; moreover, the drug was effective in
      normalizing vestibular innervation sensitivity.

PMID- 29334799
TI  - Potential of EPR spin-trapping to investigate in situ free radicals generation
      from skin allergens in reconstructed human epidermis: cumene hydroperoxide as
      proof of concept.
AB  - The first step in the development of skin sensitisation to a chemical, and in the
      elicitation of further allergic contact dermatitis (ACD), is the binding of the
      allergen to skin proteins after penetrating into the epidermis. The so-formed
      antigenic adduct is then recognised by the immune system as foreign to the body.
      Sensitising organic hydroperoxides derived from autoxidation of natural terpenes
      are believed to form antigens through radical-mediated mechanisms, although this
      has not yet been established. So far, in vitro investigations on reactive radical
      intermediates derived from these skin sensitisers have been conducted in
      solution, yet with experimental conditions being far away from real-life
      sensitisation. Herein, we report for the first time, the potential use of EPR
      spin-trapping to study the in situ generation of free radicals derived from
      cumene hydroperoxide CumOOH in a 3D reconstructed human epidermis (RHE) model,
      thus much closer to what may happen in vivo. Among the undesirable effects
      associated with dermal exposure to CumOOH, it is described to cause allergic and
      irritant dermatitis, being reported as a significant sensitiser. We considered
      exploiting the usage of spin-trap DEPMPO as an extensive view of all sort of
      radicals derived from CumOOH were observed all at once in solution. We showed
      that in the EpiskinTM RHE model, both by incubating in the assay medium and by
      topical application, carbon radicals are mainly formed by redox reactions
      suggesting the key role of CumOOH-derived carbon radicals in the antigen
      formation process.

PMID- 29334801
TI  - Bu-Shen-Yi-Qi formula impairs cytotoxicity of NK cells by up-regulating IDO
      expression in trophoblasts.
AB  - Recurrent spontaneous abortion (RSA) is a common health problem that affects
      about 5% of fertile women, when it occurs for unknown reasons, it is called
      unexplained recurrent spontaneous abortion (URSA). Traditional Chinese medicine,
      such as Bu-Shen-Yi-Qi formula which consists of Dangshen, Tusizi, Baizhu,
      Baishuo, Duzhong, Sangjisheng, Sugeng, and Tiaohuangqin, has played an invaluable
      role in the treatment of RSA since ancient times. However, the mechanism of how
      it takes effect is still not clear. To identify Bu-Shen-Yi-Qi formula could
      modulate immune condition at maternal-fetal interface via its effect on
      trophoblasts, HTR-8 of different treatment were co-cultured with peripheral or
      decidual natural killer (NK) cells, and the receptors such as NKP30 and NKP46
      expression on NK cells were measured by flow cytometry (FCM). In this study, we
      found that herb medium could increase the IDO expression at appropriate
      concentrations. As an inhibitor of IDO, 1-MT could impair the inhibitory function
      of trophoblasts on NK cells. Furthermore, Bu-Shen-Yi-Qi formula could enhance the
      inhibitory function of trophoblasts on NK cells. In conclusion, Bu-Shen-Yi-Qi
      formula can inhibit NK cytotoxicity by up-regulating IDO expression in
      trophoblasts and play a role in the treatment of URSA patients.

PMID- 29334802
TI  - Youth and young adults with acquired brain injury transition towards work-related
      roles: a qualitative study.
AB  - PURPOSE: The purpose of this research was to explore the experiences of youth and
      young adults with acquired brain injury as they transition towards work-related
      roles. Little is known about employment experiences among this age group.
      Understanding their perspectives can inform programs and clinical practice.
      MATERIALS AND METHODS: A descriptive qualitative design, including semi
      structured interviews with 14 participants (8 females; 6 males) was used.
      Interviews were transcribed verbatim and analyzed using an open-coding, thematic
      approach. RESULTS: Three major themes emerged related to the experience of work
      related roles: (1) getting to know the new me; (2) navigating support systems;
      and (3) taking control of my experience. Some participants used coping strategies
      to acquire and/or maintain work-related roles, while others felt limited by their
      condition. CONCLUSIONS: A variety of work-related roles, people, and environments
      directly and indirectly influenced the work-related transition of youth and young
      adults with acquired brain injury. Individuals expressed the importance of
      acquired brain injury awareness in informing others about their impairments. In
      fact, a lack of acquired brain injury awareness was often a main reason for
      receiving less than adequate support and accommodations. Without an understanding
      of acquired brain injury, people in the lives of these individuals were unable to
      perceive the legitimacy of acquired brain injury-related impairments.
      Implications for rehabilitation The purpose of this study is to understand the
      experiences of youth and young adults with acquired brain injury as they
      transition into work-related roles. Using these experiences as a guideline can
      promote acquired brain injury awareness, and contribute to how current
      interventions are designed and delivered. Clinicians should ensure that youth and
      young adults with acquired brain injury have access to the resources they need to
      maximize their independence. Healthcare professionals can play a pivotal role in
      relaying important acquired brain injury-related education, implementing suitable
      treatment plans, and providing them with effective tips to help them through
      their transition. A healthy transition to work-related roles should include ample
      social support and communication, acquired brain injury-related information that
      informs the community of acquired brain injury impairments, needs, and recovery
      trajectory, as well as adequate and consistent coordination within and between
      the person and the environment.

PMID- 29334800
TI  - Research progress of self-assembled nanogel and hybrid hydrogel systems based on
      pullulan derivatives.
AB  - Polymer nano-sized hydrogels (nanogels) as drug delivery carriers have been
      investigated over the last few decades. Pullulan, a nontoxic and nonimmunogenic
      hydrophilic polysaccharide derived from fermentation of black yeast like
      Aureobasidium pullulans with great biocompatibility and biodegradability, is one
      of the most attractive carriers for drug delivery systems. In this review, we
      describe the preparation, characterization, and 'switch-on/off' mechanism of
      typical pullulan self-assembled nanogels (self-nanogels), and then introduce the
      development of hybrid hydrogels that are numerous resources applied for
      regenerative medicine. A major section is used for biomedical applications of
      different nanogel systems based on modified pullulan, which exert smart stimuli
      responses at ambient conditions such as charge, pH, temperature, light, and
      redox. Pullulan self-nanogels have found increasingly extensive application in
      protein delivery, tissue engineering, vaccine development, cancer therapy, and
      biological imaging. Functional groups are incorporated into self-nanogels and
      contribute to expressing desirable results such as targeting and modified
      release. Various molecules, especially insoluble or unstable drugs and
      encapsulated proteins, present improved solubility and bioavailability as well as
      reduced side effects when incorporated into self-nanogels. Finally, the
      advantages and disadvantages of pullulan self-nanogels will be analyzed
      accordingly, and the development of pullulan nanogel systems will be reviewed.

PMID- 29334803
TI  - In vitro fermentation of gum acacia - impact on the faecal microbiota.
AB  - Interest in the consumption of gum acacia (GA) has been associated with
      beneficial health effects, which may be mediated in part by prebiotic activity.
      Two doses of GA and fructooligosaccharide (FOS) (1 and 2%) were tested for their
      efficacy over 48 h in pH- and temperature-controlled anaerobic batch cultures
      inoculated with human faeces. Samples were taken after 0, 5, 10, 24 and 48 h of
      fermentation. The selective effects of GA (increases in Bifidobacterium spp. and
      Lactobacillus spp.) were similar to those of the known prebiotic FOS. The 1% dose
      of substrates showed more enhanced selectivity compared to the 2% dose. The
      fermentation of GA also led to SCFA production, specifically increased acetate
      after 10, 24 and 48 h of fermentation, propionate after 48 h and butyrate after
      24 and 48 h. In addition, FOS led to significant increase in the main SCFAs.
      These results suggest that GA displays potential prebiotic properties.

PMID- 29334804
TI  - Characterizing on-road driving performance in individuals with traumatic brain
      injury who pass or fail an on-road driving assessment.
AB  - OBJECTIVE: To characterise on-road driving performance in individuals with
      traumatic brain injury who fail on-road driving assessment, compared with both
      those who pass assessment and healthy controls, and the injury and cognitive
      factors associated with driving performance. STUDY DESIGN: Cross-sectional.
      METHODS: Forty eight participants with traumatic brain injury (Age M = 40.50 SD =
      14.62, 77% male, post-traumatic amnesia days M = 28.74 SD =27.68) and 48 healthy
      matched controls completed a standardised on-road driving assessment in addition
      to cognitive measures. RESULTS: Individuals with traumatic brain injury who
      passed on-road driving assessment performed no differently from controls while
      individuals with traumatic brain injury who failed the assessment demonstrated
      significantly worse driving performance relative to controls across a range of
      driving manoeuvres and error types including observation of on-road environment,
      speed control, gap selection, lane position, following distance and basic car
      control. Longer time post-injury and reduced visual perception were both
      significantly correlated with reduced driving skills. CONCLUSIONS: This
      exploratory study indicated that drivers with traumatic brain injury who failed
      on-road assessment demonstrated a heterogeneous pattern of impaired driving
      manoeuvres, characterised by skill deficits across both operational (e.g., basic
      car control and lane position) and tactical domains (e.g., following distance,
      gap selection, and observation) of driving. These preliminary findings can be
      used for implementation of future driving assessments and rehabilitation
      programs. Implications for rehabilitation Clinicians should be aware that the
      majority of individuals with traumatic brain injury were deemed fit to resume
      driving following formal on-road assessment, despite having moderate to very
      severe traumatic brain injuries. Drivers with traumatic brain injury who failed
      an on-road assessment demonstrated a heterogeneous pattern of impaired skills
      including errors with observation, speed regulation, gap selection, and vehicle
      control and accordingly had difficulty executing a diverse range of common
      driving manoeuvres. Comprehensive, formal on-road assessments, incorporating a
      range of skills, and manoeuvres, are needed to evaluate readiness to return to
      driving following traumatic brain injury. Individually tailored driver
      rehabilitation programs need to address these heterogeneous skill deficits to
      best support individuals to make a successful return to driving post-traumatic
      brain injury.

PMID- 29334806
TI  - Effect of scuba diving on the oxidant/antioxidant status, SIRT1 and SIRT3
      expression in recreational divers after a winter nondive period.
AB  - The aim of this study was to examine the effects of scuba diving on oxidative
      damage markers in erythrocytes and plasma, antioxidant system in peripheral blood
      mononuclear cells (PBMCs), as well as sirtuin 1 (SIRT1) and sirtuin 3 (SIRT3)
      gene expressions in recreational divers after a winter nondive period (at least 5
      months). For that purpose, 17 male recreational divers performed an immersion at
      a depth of 30 m for 30 min. Blood samples were collected immediately before and
      after diving, 3 and 6 h after diving. Erythrocyte lipid peroxidation measured by
      thiobarbituric-reactive substances (TBARS) method was significantly increased
      immediately after diving, but returned to the baseline 6 h after diving, while no
      significant change was found for plasma TBARS and protein carbonyl derivates in
      both plasma and erythrocytes. Diving-induced catalase (CAT), superoxide dismutase
      2 (SOD2), and consequently total superoxide dismutase (SOD) activities in the
      PBMC samples (significantly increased immediately after diving, reached the
      maximum activities 3 h after diving, while 6 h after diving only CAT activity
      remained significantly increased). No significant change was observed for SOD1
      activity and gene expression, as well as SOD2 expression, while CAT and SIRT1
      expressions were slightly decreased immediately after diving and 3 h after
      diving. Interestingly, SIRT3 expression was significantly increased 6 h after
      diving. In conclusion, after the first dive to 30 m after a nondive season,
      activation of antioxidant defence was not sufficient to prevent oxidative damage,
      while SIRT3 upregulation could be a step towards an adaptive response to the
      diving.

PMID- 29334807
TI  - Methodologies for the airbrush application of MALDI matrices.
AB  - There is still a need to develop reliable and robust matrix deposition methods
      for matrix-assisted laser desorption/ionisation mass spectrometry that are
      applicable to a range of matrices, solvents and analyte types. This paper
      presents a robust methodology for the airbrush application of matrices along with
      the implications of varying the set-up and airbrush parameters. A small number of
      organic analytes and metal salts are analysed in both positive and negative ion
      modes to exemplify this methodology. In the analyses with the airbrush deposited
      matrices, performance was enhanced when compared to standard pipette deposition
      with the need for a search for sweat spots greatly diminished due to the increase
      homogeneity of the matrix surface and resultant analyte spots. As expected, the
      graphite matrices were shown to specifically outperform the organic matrices in
      negative ion mode.

PMID- 29334805
TI  - Delivery of radix ophiopogonis polysaccharide via sucrose acetateisobutyrate
      based in situ forming systems alone or combined with itsmono-PEGylation.
AB  - This work aimed to achieve long-lasting delivery of radix ophiopogonis
      polysaccharide (ROP) by sucrose acetate isobutyrate (SAIB)-based in situ forming
      systems (ISFSs) alone or combined with mono-PEGylation of ROP. When the
      '90%SAIB/10% solvent' system was used, the mean residence time (MRT) of ROP was
      prolonged by 4.3 5 ~ 7.00 times and the initial release rate was reduced
      significantly. However, this system was only suitable for days-long sustained
      release of ROP in short-term therapy. As to the 'SAIB/additives/solvent' system
      containing mono-PEGylated ROP, the results indicated that SAIB/poly(d,l-lactide
      co-glycolide) (PLGA)/N-methyl-2-pyrrolidone (NMP) was superior to SAIB/polylactic
      acid (PLA)/NMP and SAIB/PLA/ethanol in controlled release. Moreover, weeks- to
      months-long (16-60 d) smooth release of ROP could be achieved by varying the
      concentration (10-30%) and molecular weight (MW) of PLGA (10-50 kDa) or by
      employing a moderate MW of PEGylated ROP (~20 or ~30 kDa). With further
      increasing the conjugate MW to ~40 kDa, the contribution of drug elimination to
      its plasma retention seemed to surpass that of the SAIB-based system, resulting
      in that the system no longer had an obvious influence on the in vivo behavior of
      the conjugate. Besides, the results of host response confirmed that with less
      solvent being used, the SAIB-based systems showed a higher biocompatibility than
      the PLGA-based systems, suggesting that they could be freely chosen in the
      prevention and/or cure of chronic diseases.

PMID- 29334808
TI  - Identification of a novel site of interaction between ataxin-3 and the amyloid
      aggregation inhibitor polyglutamine binding peptide 1.
AB  - Amyloid diseases represent a growing social and economic burden in the developed
      world. Understanding the assembly pathway and the inhibition of amyloid formation
      is key to developing therapies to treat these diseases. The neurodegenerative
      condition Machado-Joseph disease is characterised by the self-aggregation of the
      protein ataxin-3. Ataxin-3 consists of a globular N-terminal Josephin domain,
      which can aggregate into curvilinear protofibrils, and an unstructured,
      dynamically disordered C-terminal domain containing three ubiquitin interacting
      motifs separated by a polyglutamine stretch. Upon expansion of the polyglutamine
      region above 50 residues, ataxin-3 undergoes a second stage of aggregation in
      which long, straight amyloid fibrils form. A peptide inhibitor of polyglutamine
      aggregation, known as polyQ binding peptide 1, has been shown previously to
      prevent the maturation of ataxin-3 fibrils. However, the mechanism of this
      inhibition remains unclear. Using nanoelectrospray ionisation-mass spectrometry,
      we demonstrate that polyQ binding peptide 1 binds to monomeric ataxin-3. By
      investigating the ability of polyQ binding peptide 1 to bind to truncated ataxin
      3 constructs lacking one or more domains, we localise the site of this
      interaction to a 39-residue sequence immediately C-terminal to the Josephin
      domain. The results suggest a new mechanism for the inhibition of polyglutamine
      aggregation by polyQ binding peptide 1 in which binding to a region outside of
      the polyglutamine tract can prevent fibril formation, highlighting the importance
      of polyglutamine flanking regions in controlling aggregation and disease.

PMID- 29334809
TI  - Accidental pharmacological poisonings in young children: population-based study
      in three settings.
AB  - INTRODUCTION: Pharmacological poisonings in young children are avoidable.
      Previous studies report calls to poisons centres, presentations to emergency
      departments (ED) or hospital admissions. There are limited data assessing
      concurrent management of poisonings across all three settings. We aimed to
      describe accidental pharmacological poisonings in young children across our
      Poisons Information Centre (PIC), EDs and hospitals. METHODS: A population-based
      study in New South Wales, Australia, of PIC calls, ED presentations and hospital
      admissions for accidental pharmacological poisoning in children aged <5 years,
      2007-2013. We examined trends, medicines responsible and subsequent management.
      Medicines were coded using ICD10-AM diagnosis codes (T36-50). RESULTS: Over 2007
      2013, pharmacological poisonings accounted for 67,816 PIC calls, 7739 ED
      presentations and 2082 admissions. Rates (per 10,000 children) of PIC calls
      declined from 220 to 178; ED presentations were stable (~22-24), with a decrease
      in emergency cases offset by an increase in semi- or non-urgent presentations;
      hospital admissions declined (8-5). Most PIC calls related to "non-opioid
      analgesics" (25%), and "topical agents" (18%). Nearly every day, one child aged
      <5 years was admitted to hospital for poisoning. "Benzodiazepines", "other and
      unspecified antidepressants", "uncategorised antihypertensives", and "4
      aminophenol derivatives" accounted for over one-third of all admissions. Most PIC
      calls (90%) were advised to stay home, 6% referred to hospital. One-quarter of ED
      presentations resulted in admission. CONCLUSIONS: Poisonings reported to PIC and
      hospitals declined, however, non-urgent ED presentations increased. Strategies to
      reduce therapeutic errors and access to medicines, and education campaigns to
      improve Poisons Centre call rates to prevent unnecessary ED presentations are
      needed.

PMID- 29334810
TI  - Monitoring of Metabolic Adverse Effects Associated With Atypical Antipsychotics
      Use in an Outpatient Psychiatric Clinic.
AB  - BACKGROUND: Atypical antipsychotics are associated with metabolic complications
      that contribute to a higher risk of cardiovascular disease. Current evidence
      reveal suboptimal adherence to the complex and variable official recommendations
      on metabolic monitoring in the corresponding patient population. A study
      evaluating metabolic monitoring at guideline-recommended intervals may help
      identify areas for intervention. OBJECTIVE: Describe the frequency of monitoring
      metabolic adverse effects in patients receiving atypical antipsychotics in an
      outpatient psychiatric clinic with respect to the specific guideline-recommended
      intervals. METHODS: A retrospective chart review was conducted in the outpatient
      psychiatric clinic. The primary outcome measure was the percentage of patients
      monitored for metabolic parameters at the current guideline-recommended
      intervals. The secondary end points were the percentage of patients with
      documented primary care physician, untreated metabolic comorbidities, and treated
      metabolic comorbidities by disease state. RESULTS: The most assessed parameters
      were family history (98%), blood pressure (81%), and body mass index/body weight
      (83%) at the baseline interval. The least assessed parameters were lipids (14%)
      at the 12-week interval and waist circumference (0%) at any interval. CONCLUSION:
      Interventions are needed to encourage higher compliance with current
      recommendations. The complexity of the recommendations is the most likely reason
      for the suboptimal compliance.

PMID- 29334811
TI  - The experiences of physical rehabilitation in individuals with spinal cord
      injuries: a qualitative thematic synthesis.
AB  - PURPOSE: The purpose of this thematic synthesis review was to identify and
      synthesise published qualitative research on the perspectives of individuals with
      spinal cord injuries with respect to physical rehabilitation interventions.
      MATERIALS AND METHODS: The peer-reviewed literature was searched across seven
      databases and identified abstracts were independently screened by two reviewers.
      A thematic synthesis methodology was used to code and synthesise the results from
      the included studies. RESULTS: In total, 7233 abstracts were identified; 31
      articles were selected for inclusion, representing 26 physical rehabilitation
      interventions. The methodological quality of studies was moderate (Standards for
      Reporting Qualitative Research mean +/- standard deviation = 14.39 +/- 3.61). The
      four main themes developed were: (1) Benefits of physical rehabilitation, (2)
      Challenges of physical rehabilitation, (3) Need for support, and (4) Issue of
      control. CONCLUSIONS: This qualitative thematic synthesis provides key insights
      into the experiences of individuals with spinal cord injuries who received
      physical rehabilitation. Recommendations for practice, based on the findings,
      include creating a diverse, encouraging, and educational physical rehabilitation
      experience with supportive staff who focus on communication and person-centred
      care. Implications for Rehabilitation Physical rehabilitation provides
      psychological as well as physical benefits to people with spinal cord injuries,
      including motivation, hope, improved self-confidence, and acceptance. Challenges
      identified during physical rehabilitation for people with spinal cord injuries,
      such as comparisons, negative emotions, recovery expectations, and slow progress,
      should be addressed by healthcare professionals to ensure person-centred care.
      People with spinal cord injuries identified a need for support from health care
      professionals, family, and friends, as well other people with spinal cord
      injuries. There is an issue of control in physical rehabilitation for people with
      spinal cord injuries, which can result in a fight with oneself or with healthcare
      professionals to regain the control that has been lost.

PMID- 29334812
TI  - Anti-biofilm effect of a butenolide/polymer coating and metatranscriptomic
      analyses.
AB  - Butenolide is an environmentally friendly antifouling natural product, but its
      efficiency and mechanism in preventing biofilm formation have not been examined.
      Furthermore, controlling the release of butenolide from paints into seawater is
      technically challenging. A coating was developed by mixing butenolide with a
      biodegradable polymer, poly (epsilon-caprolactone)-based polyurethane, and a one
      month in situ anti-biofilm test was conducted in a subtidal area. The constant
      release of butenolide from the surface suggested that its release was well
      controlled. Direct observation and confocal microscope investigation indicated
      that the coating was effective against both biofilm formation and attachment of
      large fouling organisms. Metatranscriptomic analysis of biofilm samples implied
      that the coating selectively inhibited the adhesion of microbes from a variety of
      phyla and targeted particular functional pathways including energy metabolism,
      drug transport and toxin release. These integrated analyses demonstrated the
      potential application of this butenolide/polymer coating as an anti-biofilm
      material.

PMID- 29334813
TI  - Reduction of bacterial adhesion on titanium-doped diamond-like carbon coatings.
AB  - A range of titanium doped diamond-like carbon (Ti-DLC) coatings with different Ti
      contents were prepared on stainless steel substrates using a plasma-enhanced
      chemical vapour deposition technique. It was found that both the electron donor
      surface energy and the surface roughness of the Ti-DLC coatings increased with
      increasing Ti contents in the coatings. Bacterial adhesion to the coatings was
      evaluated against Escherichia coli WT F1693 and Pseudomonas aeruginosa ATCC
      33347. The experimental data showed that bacterial adhesion decreased with the
      increases of the Ti content, the electron donor surface energy and surface
      roughness of the coatings, while the bacterial removal percentage increased with
      the increases of these parameters. The Ti-DLC coatings reduced bacterial
      attachment by up to 75% and increased bacterial detachment from 15 to 45%,
      compared with stainless steel control.

PMID- 29334815
TI  - Impact of medication adherence on risk of ischemic stroke, major bleeding and
      deep vein thrombosis in atrial fibrillation patients using novel oral
      anticoagulants.
AB  - OBJECTIVES: Our study examined the impact of adherence to novel oral
      anticoagulants [NOACs - dabigatran and rivaroxaban] on ischemic-stroke (IS),
      major-bleeding (MB), deep-vein-thrombosis and pulmonary-embolism (DVTPE) risk in
      a large, nationwide, propensity-matched sample. METHODS: A retrospective cohort
      study utilized data from a US commercial managed-care database (2010-2012). Adult
      patients with >=1 diagnosis of atrial fibrillation/flutter (ICD-9 427.31/32), >1
      prescription of NOACs and CHA2DS2-VASc score >=1 were included. Patients were
      categorized as adherent versus nonadherent (using proportion of days covered [PDC
      >=80%]) based on their NOAC use up to 6 months and those continued its use up to
      12 months. The patients were matched using propensity score (based on inverse
      probability treatment weighting) and the risk of IS, MB, DVTPE outcomes was
      evaluated for the matched cohorts' post-adherence (exposure) assessment using
      multivariable Cox regression. RESULTS: A total of 3,629 and 1,946 patients with
      at least 6 and 12 months of NOAC use were included. Based on a PDC threshold of
      >=80%, adherence rates at 6 and 12 month usage were 77% and 76%, respectively.
      Patients with lowest adherence were from the South, had low stroke risk and
      EPO/HMO insurance. Using Cox models with matched cohorts, nonadherence within the
      first 6 months' use was significantly associated with higher risk of IS and DVTPE
      (IS: hazard ratio [HR] = 1.82, p = .002; DVTPE: HR = 2.12, p = .010) and the risk
      increased with nonadherence for the prolonged period of 12 months' use (IS: HR =
      2.08, p = .022; DVTPE: HR = 5.39, p = .003). The risk of MB was not different (p
      > .05) between adherent and nonadherent groups for both 6 month and 12 month
      cohorts. CONCLUSION: Adherence to NOACs for both 6 months and prolonged use (up
      to 12 months) was associated with a reduction in IS and DVTPE risk, but did not
      substantially increase risk of MB. Further studies on newer, individual NOACs and
      older populations are warranted.

PMID- 29334814
TI  - Dual-ligand modified liposomes provide effective local targeted delivery of lung
      cancer drug by antibody and tumor lineage-homing cell-penetrating peptide.
AB  - The abilities of a drug delivery system to target and penetrate tumor masses are
      key factors in determining the system's chemotherapeutic efficacy. Here, we
      explored the utility of an anti-carbonic anhydrase IX (anti-CA IX) antibody and
      CPP33 dual-ligand modified triptolide-loaded liposomes (dl-TPL-lip) to
      simultaneously enhance the tumor-specific targeting and increase tumor cell
      penetration of TPL. In vitro, the dl-TPL-lip increased the cytotoxicity of TPL in
      CA IX-positive lung cancer cells, which showed tunable size (137.6 +/- 0.8 nm),
      high-encapsulation efficiency (86.3 +/- 2.6%) and sustained release. Dl-TPL-lip
      significantly improved the ability of liposomes to penetrate 3 D tumor spheroids
      and exhibited a superior inhibiting effect. Furthermore, pharmacokinetic studies
      in rats that received TPL liposomal formulations by endotracheal administration
      showed a reduced concentration of TPL (17.3%-30.6% compared to free TPL) in
      systemic circulation. After pulmonary administration in orthotopic lung tumor
      bearing mice, dl-TPL-lip significantly enhanced TPL anti-cancer efficacy without
      apparent systemic toxicity. This dual-ligand modified liposomal vehicle presents
      a potential system for localized and targeted delivery of anti-cancer drugs to
      improve their efficacy.

PMID- 29334816
TI  - Anti-colchicine Fab fragments prevent lethal colchicine toxicity in a porcine
      model: a pharmacokinetic and clinical study.
AB  - BACKGROUND: Colchicine poisoning is commonly lethal. Colchicine-specific Fab
      fragments increase rat urinary colchicine clearance and have been associated with
      a good outcome in one patient. We aimed to develop a porcine model of colchicine
      toxicity to study the pharmacokinetics and efficacy of ovine Fab. METHODS: A
      Gottingen minipig critical care model was established and serial blood samples
      taken for colchicine and Fab pharmacokinetics, clinical chemistry, and
      haematology. Animals were euthanised when the mean arterial pressure fell below
      45 mmHg without response to vasopressor, or at study completion. RESULTS: Initial
      studies indicated that oral dosing produced variable pharmacokinetics and time-to
      euthanasia. By contrast, intravenous infusion of 0.25 mg/kg colchicine over 1 h
      produced reproducible pharmacokinetics (AUC0-20 343 [SD = 21] ug/L/h), acute
      multi-organ injury, and cardiotoxicity requiring euthanasia a mean of 22.5 (SD =
      3.2) h after dosing. A full-neutralising equimolar Fab dose given 6 h after the
      infusion (50% first hour, 50% next 6 h [to reduce renal-loss of unbound Fab])
      produced a 7.35-fold increase in plasma colchicine (AUC0-20 2,522 [SD = 14]
      ug/L/h), and removed all free plasma colchicine, but did not prevent toxicity
      (euthanasia at 29.1 [SD = 3.4] h). Earlier administration over 1 h of the full
      neutralising dose, 1 or 3 h after the colchicine, produced a 12.9-fold (AUC0-20
      4,433 [SD = 607] ug/L/h) and 6.0-fold (AUC0-20 2,047 [SD = 51] ug/L/h) increase
      in plasma colchicine, respectively, absence of free plasma colchicine until 20 h,
      and survival to study end without marked cardiotoxicity. CONCLUSIONS: Colchicine
      specific Fab given early, in equimolar dose, bound colchicine, eliciting its
      movement into the blood, and preventing severe toxicity. Clinical studies are now
      needed to determine how soon this antidote must be given to work in human
      poisoning.

PMID- 29334817
TI  - QuantiFERON-plus does not discriminate between active and latent tuberculosis.

PMID- 29334818
TI  - Relationship between nurses' moral sensitivity and the quality of care.
AB  - BACKGROUND: To provide care with high quality, nurses face a number of moral
      issues requiring them to have moral abilities in professional performance. Moral
      sensitivity is the first step in moral performance. However, its relation to the
      quality of care patients receive is controversial. RESEARCH OBJECTIVE: This study
      aims to determine the relationship between the moral sensitivity of nurses and
      the quality of care received by patients in the medical wards. RESEARCH DESIGN: A
      descriptive correlational study using validated tools, including Moral
      Sensitivity Questionnaire and the Quality Patient Quality Scale. Participants and
      research context: In total, 198 nurses and 198 patients in 17 medical wards of
      hospitals affiliated with Tabriz University of Medical Sciences, Iran. Ethical
      considerations: The study was reviewed and approved by the Ethics Committee of
      Tabriz University of Medical Sciences. FINDINGS: The mean values of nurses' moral
      sensitivity and nurses' quality care were 136.47 +/- 13.30 and 196.36 +/- 44.10,
      respectively. There was no significant relationship between the patient care
      quality and nurses' moral sensitivity ( r = -.14, p = .5). However, there was a
      significant inverse relationship between the dimension of "Experiencing moral
      conflicts" and the overall score of quality care ( r = -.50, p = .04), the
      dimensions of "psychosocial ( r = -.50, p = .04)" and "physical ( r = -.50, p =
      .03)." CONCLUSION: Considering the significant inverse relationship between the
      score of patient quality care and the dimension of moral conflict experience, it
      seems when nurses make moral decisions, they experience a conflict between
      personal and professional values in their careers and thus experience moral
      tension. If this tension is not resolved properly, it can provide a way for them
      to distance themselves from patients, thereby making nurses indifferent to moral
      care.

PMID- 29334819
TI  - Management of Hodgkin lymphoma in the era of brentuximab vedotin: real-world data
      from five European countries.
AB  - We examined real-world data on management of relapsed/refractory Hodgkin lymphoma
      (R/R HL) in five European countries and the consistency of these data with
      guideline recommendations. Retrospective clinical and epidemiologic data for 509
      patients with R/R HL treated between January 2014 and March 2015 were collected
      at centers in France, Germany, Italy, Spain, and the United Kingdom. Mean age was
      46.3 years; 73.3% were receiving second-line therapy for a first relapse during
      the reporting period. Most patients received ABVD as front-line chemotherapy,
      except in Germany where escalated BEACOPP was used more often. The proportion of
      patients receiving stem cell transplantation (SCT) was 44%; 85% of transplants
      occurred at first relapse. Brentuximab vedotin (BV) was usually administered
      after autologous SCT, and was initiated for 65% of patients following SCT
      failure. Our findings suggest that R/R HL management across these countries is
      broadly consistent with guideline recommendations and that BV is well-integrated
      into treatment pathways.

PMID- 29334820
TI  - EMT does not work regular shifts.

PMID- 29334821
TI  - Development and validation of a facial expression database based on the
      dimensional and categorical model of emotions.
AB  - The present study describes the development and validation of a facial expression
      database comprising five different horizontal face angles in dynamic and static
      presentations. The database includes twelve expression types portrayed by eight
      Japanese models. This database was inspired by the dimensional and categorical
      model of emotions: surprise, fear, sadness, anger with open mouth, anger with
      closed mouth, disgust with open mouth, disgust with closed mouth, excitement,
      happiness, relaxation, sleepiness, and neutral (static only). The expressions
      were validated using emotion classification and Affect Grid rating tasks
      [Russell, Weiss, & Mendelsohn, 1989. Affect Grid: A single-item scale of pleasure
      and arousal. Journal of Personality and Social Psychology, 57(3), 493-502]. The
      results indicate that most of the expressions were recognised as the intended
      emotions and could systematically represent affective valence and arousal.
      Furthermore, face angle and facial motion information influenced emotion
      classification and valence and arousal ratings. Our database will be available
      online at the following URL. https://www.dh.aist.go.jp/database/face2017/ .

PMID- 29334822
TI  - Vibsanol A induces differentiation of acute myeloid leukemia cells via activation
      of the PKC signaling pathway and induction of ROS.
AB  - Identifying novel differentiating agents to promote leukemia-cell differentiation
      is a pressing need. Here, we demonstrated that vibsanol A, a vibsane-type
      diterpenoid, inhibited the growth of acute myeloid leukemia (AML) cells via
      induction of cell differentiation, which was characterized by G1 cell cycle
      arrest. The differentiation-inducing effects of vibsanol A were dependent upon
      protein kinase C (PKC) activation, and subsequent activation of the extracellular
      signal-regulated kinase (ERK) pathway. Furthermore, vibsanol A treatment
      increased reactive oxygen species (ROS) levels, and the ROS scavenger NAC
      reversed the vibsanol A-induced cell differentiation, indicating an important
      role for ROS in the action of vibsanol A. Finally, vibsanol A exhibited a
      differentiation-enhancing effect when used in combination with all-trans retinoic
      acid in AML cells. Overall results suggested that vibsanol A induces AML cell
      differentiation via activation of the PKC/ERK signaling and induction of ROS.
      Vibsanol A may prove to be an effective differentiating agent against AML.

PMID- 29334823
TI  - A New Genus of Tapeworm (Cestoda: Onchoproteocephalidea) from Sawfish
      (Elasmobranchii: Pristidae).
AB  - Collections from the dwarf sawfish, Pristis clavata, near Darwin, Australia, in
      1997 led to the discovery of the new onchoproteocephalidean genus Matticestus n.
      gen.-a taxon that has been referred to in molecular phylogenetic analyses in
      which it has been included as "New genus 8." Its type species, Matticestus anneae
      n. gen., n. sp., and a second species, Matticestus kathleenae n. sp., are
      described. Placement of this taxon in the Onchoproteocephalidea is supported
      morphologically in that both species bear a scolex with 4 bothridia each with a
      pair of bi-pronged hooks and spinitriches that extend throughout the length of
      the body. Sequence data for the D1-D3 region of the 28S rDNA gene also place the
      genus solidly among the other elasmobranch-hosted members of the order. The new
      genus differs from the other elasmobranch-hosted genera in the order in that its
      members possess a combination of biloculated bothridia with lateral lappets on
      the posterior margin of the anterior loculus and a pair of bi-pronged hooks with
      a distinctive configuration of tubercles and internal channels. Its members are
      also extremely small. In summary, Matticestus n. gen. is an unusually tiny,
      "spiny," genus of cestode that seems to exclusively parasitize sawfish of the
      genus Pristis.

PMID- 29334824
TI  - #MeToo - a concern for general practice?

PMID- 29334825
TI  - The Influence of Traumatic Axonal Injury in Thalamus and Brainstem on Level of
      Consciousness at Scene or Admission: A Clinical Magnetic Resonance Imaging Study.
AB  - The aim of this study was to investigate how traumatic axonal injury (TAI)
      lesions in the thalamus, basal ganglia, and brainstem on clinical brain magnetic
      resonance imaging (MRI) are associated with level of consciousness in the acute
      phase in patients with moderate to severe traumatic brain injury (TBI). There
      were 158 patients with moderate to severe TBI (7-70 years) with early 1.5T MRI
      (median 7 days, range 0-35) without mass lesion included prospectively. Glasgow
      Coma Scale (GCS) scores were registered before intubation or at admission. The
      TAI lesions were identified in T2*gradient echo, fluid attenuated inversion
      recovery, and diffusion weighted imaging scans. In addition to registering TAI
      lesions in hemispheric white matter and the corpus callosum, TAI lesions in the
      thalamus, basal ganglia, and brainstem were classified as uni- or bilateral.
      Twenty percent of patients had TAI lesions in the thalamus (7% bilateral), 18% in
      basal ganglia (2% bilateral), and 29% in the brainstem (9% bilateral). One of 26
      bilateral lesions in the thalamus or brainstem was found on computed tomography.
      The GCS scores were lower in patients with bilateral lesions in the thalamus
      (median four) and brainstem (median five) than in those with corresponding
      unilateral lesions (median six and eight, p = 0.002 and 0.022). The TAI locations
      most associated with low GCS scores in univariable ordinal regression analyses
      were bilateral TAI lesions in the thalamus (odds ratio [OR] 35.8; confidence
      interval [CI: 10.5-121.8], p < 0.001), followed by bilateral lesions in basal
      ganglia (OR 13.1 [CI: 2.0-88.2], p = 0.008) and bilateral lesions in the
      brainstem (OR 11.4 [CI: 4.0-32.2], p < 0.001). This Trondheim TBI study showed
      that patients with bilateral TAI lesions in the thalamus, basal ganglia, or
      brainstem had particularly low consciousness at admission. We suggest these
      bilateral lesions should be evaluated further as possible biomarkers in a new TAI
      MRI classification as a worst grade, because they could explain low consciousness
      in patients without mass lesions.

PMID- 29334827
TI  - Left Ventricular Pseudoaneurysms in Children-A Case Series.
AB  - Left ventricular pseudoaneurysms are very rare in children. In children, left
      ventricular pseudoaneurysms can occur following infection, trauma, ischemia, or
      cardiac surgery. The authors report a series of three cases treated at our
      hospital with two of the cases having a history of extrapulmonary tuberculosis
      and one patient with a history of varicella zoster infection.

PMID- 29334826
TI  - Patient safety culture in out-of-hours primary care services in the Netherlands:
      a cross-sectional survey.
AB  - OBJECTIVE: To examine patient safety culture in Dutch out-of-hours primary care
      using the safety attitudes questionnaire (SAQ) which includes five factors:
      teamwork climate, safety climate, job satisfaction, perceptions of management and
      communication openness. DESIGN: Cross-sectional observational study using an
      anonymous web-survey. Setting Sixteen out-of-hours general practitioner (GP)
      cooperatives and two call centers in the Netherlands. Subjects Primary healthcare
      providers in out-of-hours services. Main outcome measures Mean scores on patient
      safety culture factors; association between patient safety culture and
      profession, gender, age, and working experience. RESULTS: Overall response rate
      was 43%. A total of 784 respondents were included; mainly GPs (N = 470) and
      triage nurses (N = 189). The healthcare providers were most positive about
      teamwork climate and job satisfaction, and less about communication openness and
      safety climate. The largest variation between clinics was found on safety
      climate; the lowest on teamwork climate. Triage nurses scored significantly
      higher than GPs on each of the five patient safety factors. Older healthcare
      providers scored significantly higher than younger on safety climate and
      perceptions of management. More working experience was positively related to
      higher teamwork climate and communication openness. Gender was not associated
      with any of the patient safety factors. CONCLUSIONS: Our study showed that
      healthcare providers perceive patient safety culture in Dutch GP cooperatives
      positively, but there are differences related to the respondents' profession, age
      and working experience. Recommendations for future studies are to examine reasons
      for these differences, to examine the effects of interventions to improve safety
      culture and to make international comparisons of safety culture. Key Points
      Creating a positive patient safety culture is assumed to be a prerequisite for
      quality and safety. We found that: * healthcare providers in Dutch GP
      cooperatives perceive patient safety culture positively; * triage nurses scored
      higher than GPs, and older and more experienced healthcare professionals scored
      higher than younger and less experienced professionals - on several patient
      safety culture factors; and * within the GP cooperatives, safety climate and
      openness of communication had the largest potential for improvement.

PMID- 29334828
TI  - An Unusual Combination of Double Inlet Left Ventricle With Discordant
      Ventriculoarterial Connections and Bilateral Arterial Ducts.
AB  - The presence of bilaterally persistent arterial ducts is an uncommon abnormality.
      Here, we describe the anatomy and successful management of an unusual patient
      with bilateral ducts in the setting of double inlet left ventricle, discordant
      ventriculoarterial connections, aortic atresia, and a severely hypoplastic and
      serpentine aortic arch.

PMID- 29334829
TI  - Rare Combination of Pathologies Causing Mitral Stenosis and Mitral Regurgitation:
      A Case Report.
AB  - A supramitral ring is a rare cause of mitral stenosis, while an isolated mitral
      valve cleft is a rare cause of congenital mitral regurgitation. Fortunately, both
      the lesions are known to have good outcomes after surgical correction. Although
      each is known to be associated with a variety of other structural heart defects,
      their coexistence has not been reported previously. We report a case of a three-
      and half-year-old boy detected to have a rare combination of supramitral ring
      producing severe mitral stenosis with a coexisting cleft in the anterior leaflet
      of mitral valve causing severe mitral regurgitation. The patient underwent
      successful surgical repair with resolution of both mitral stenosis and
      regurgitation.

PMID- 29334830
TI  - Cardiopulmonary Bypass for a Patient With Congenital Hyperinsulinemia.
AB  - Congenital hyperinsulinism is a clinical syndrome of pancreatic beta-cell
      dysfunction characterized by failure to suppress insulin secretion in the
      presence of hypoglycemia. Here, we describe the concerns, the techniques used to
      ameliorate these potential problems, and the outcomes for a child with this
      condition undergoing cardiopulmonary bypass for correction of an atrial septal
      defect.

PMID- 29334831
TI  - Does Stroke Rehabilitation Really Matter? Part B: An Algorithm for Prescribing an
      Effective Intensity of Rehabilitation.
AB  - BACKGROUND: The proportional recovery rule suggests that current rehabilitation
      practices may have limited ability to influence stroke recovery. However, the
      appropriate intensity of rehabilitation needed to achieve recovery remains
      unknown. Similarities between rodent and human recovery biomarkers may allow
      determination of rehabilitation thresholds necessary to activate endogenous
      biological recovery processes. OBJECTIVE: We determined the relative influence
      that clinically relevant biomarkers of stroke recovery exert on functional
      outcome. These biomarkers were then used to generate an algorithm that prescribes
      individualized intensities of rehabilitation necessary for recovery of function.
      METHODS: A retrospective cohort of 593 male Sprague-Dawley rats was used to
      identify biomarkers that best predicted poststroke change in pellet retrieval in
      the Montoya staircase-reaching task using multiple linear regression. Prospective
      manipulation of these factors using endothelin-1-induced stroke (n = 49) was used
      to validate the model. RESULTS: Rehabilitation was necessary to reliably predict
      recovery across the continuum of stroke severity. As infarct volume and initial
      impairment increased, more intensive rehabilitation was required to engage
      recovery. In this model, we prescribed the specific dose of daily rehabilitation
      required for rats to achieve significant motor recovery using the biomarkers of
      initial poststroke impairment and infarct volume. CONCLUSIONS: Our algorithm
      demonstrates an individualized approach to stroke rehabilitation, wherein imaging
      and functional performance measures can be used to develop an optimized
      rehabilitation paradigm for rats, particularly those with severe impairments.
      Exploring this approach in human patients could lead to an increase in the
      proportion of individuals experiencing recovery of lost motor function
      poststroke.

PMID- 29334832
TI  - Novel Mortality Markers for Critically Ill Patients.
AB  - AIM: Inflammatory markers, such as the neutrophil to lymphocyte ratio (NLR) and
      platelet to lymphocyte ratio (PLR), derived from a complete blood count have
      recently attracted attention as potential markers of morbidity and mortality in
      various diseases. The aim of the present study was to assess the usefulness of
      the NLR and PLR as markers of hospital stay and mortality of patients in
      intensive care units (ICUs). METHODS: Patients treated in the ICU of our
      institution between October 2016 and August 2017 were enrolled in the study.
      After obtaining approval from the institutional committee, patient data were
      sourced from the institution's computerized database and retrospectively
      analyzed. The patients were assigned to 2 groups according to the outcomes:
      survivors and deceased. RESULTS: The NLR of survivors and deceased patients was
      2.06 (1.18-21.68) and 10.42 (2.85-48.2), respectively. The NLR was significantly
      elevated in deceased patients as compared with that of survivors ( P < .001).
      Similarly, the median PLR of patients in the deceased group (268.9 [150-3000])
      was significantly higher than that of patients in the survivor group (55.7 [11.8
      152.5]). The difference in the PLR between groups was significant ( P < .001).
      CONCLUSION: Both the NLR and PLR, as well as C-reactive protein, predicted
      mortality in this critically ill population. The PLR and NLR are easy-to-measure,
      inexpensive markers. Physicians should be aware of elevations in PLR and NLR in
      patient care in ICUs.

PMID- 29334833
TI  - Silver nanoparticles induce neurotoxicity in a human embryonic stem cell-derived
      neuron and astrocyte network.
AB  - Silver nanoparticles (AgNPs) are among the most extensively used nanoparticles
      and are found in a variety of products. This ubiquity leads to inevitable
      exposure to these particles in everyday life. However, the effects of AgNPs on
      neuron and astrocyte networks are still largely unknown. In this study, we used
      neurons and astrocytes derived from human embryonic stem cells as a cellular
      model to study the neurotoxicity that is induced by citrate-coated AgNPs (AgSCs).
      Immunostaining with the astrocyte and neuron markers, glial fibrillary acidic
      protein and microtubule-associated protein-2 (MAP2), respectively, showed that
      exposure to AgSCs at the concentration of 0.1 ug/mL increased the
      astrocyte/neuron ratio. In contrast, a higher concentration of AgSCs (5.0 ug/ml)
      significantly changed the morphology of astrocytes. These results suggest that
      astrocytes are sensitive to AgSC exposure and that low concentrations of AgSCs
      promote astrogenesis. Furthermore, our results showed that AgSCs reduced neurite
      outgrowth, decreased the expression of postsynaptic density protein 95 and
      synaptophysin, and induced neurodegeneration in a concentration-dependent manner.
      Our findings additionally suggest that the expression and phosphorylation status
      of MAP2 isoforms, as modulated by the activation of the Akt/glycogen synthase
      kinase-3/caspase-3 signaling pathway, may play an important role in AgSC-mediated
      neurotoxicity. We also found that AgNO3 exposure only slightly reduced neurite
      outgrowth and had little effect on MAP2 expression, suggesting that AgSCs and
      AgNO3 have different neuronal toxicity mechanisms. In addition, most of these
      effects were reduced when the cell culture was co-treated with AgSCs and the
      antioxidant ascorbic acid, which implies that oxidative stress is the major cause
      of AgSC-mediated astrocytic/neuronal toxicity and that antioxidants may have a
      neuroprotective effect.

PMID- 29334835
TI  - National approaches to promote sports and physical activity in adults with
      disabilities: examples from the Netherlands and Canada.
AB  - PURPOSE: This study described how the Dutch and Canadian governments promote high
      performance sports, recreational sports, and physical activity (PA) among adults
      with disabilities on a national level. METHODS: An internet-based study was
      conducted to identify and select relevant documents and websites containing
      information about the national approach to promote disability sports and physical
      activities in the Netherlands and Canada. RESULTS: Both governments promote high
      performance sports in similar ways, but use different strategies to promote
      recreational sports and physical activities. The Dutch approach is characterized
      by using time-limited programs focusing on enhancement of sports infrastructure
      and inter-sector collaboration in which municipalities have key roles. The
      Canadian government promotes recreational sports in disabled populations by
      supporting programs via bilateral agreements with provinces and territories.
      Furthermore, the level of integration of disability sports into mainstream sports
      differs between countries. CONCLUSIONS: The findings of this study may inspire
      policy makers from different countries to learn from one another's policies in
      order to optimize national approaches to promote disability sports and PA on all
      levels. Implications for rehabilitation It is recommended for policy makers of
      national governments to develop and implement policy programs that promote sports
      and physical activities among people with disabilities because of its potential
      impact on functioning, participation, quality of life, and health. Insight into
      national approaches to promote sport and physical activities is relevant for
      rehabilitation practice to understand ongoing opportunities for people with
      disabilities to stay physically active after rehabilitation through participation
      in home and/or community-based sport and physical activities. It seems worthwhile
      to integrate activities to promote sport and physical activities in
      rehabilitation in such a way that it fits with the current governmental approach.
      It is recommended to set up international collaborations to develop and share
      knowledge about effective and sustainable national approaches to promote sports
      and physical activities among people with disabilities.

PMID- 29334834
TI  - Mild Jugular Compression Collar Ameliorated Changes in Brain Activation of
      Working Memory after One Soccer Season in Female High School Athletes.
AB  - Recent neuroimaging studies have suggested that repetitive subconcussive head
      impacts, even after only one sport season, may lead to pre- to post-season
      structural and functional alterations in male high school football athletes.
      However, data on female athletes are limited. In the current investigation, we
      aimed to (1) assess the longitudinal pre- to post-season changes in functional
      MRI (fMRI) of working memory and working memory performance, (2) quantify the
      association between the pre- to post-season change in fMRI of working memory and
      the exposure to head impact and working memory performance, and (3) assess
      whether wearing a neck collar designed to reduce intracranial slosh via mild
      compression of the jugular veins can ameliorate the changes in fMRI brain
      activation observed in the female high school athletes who did not wear collars
      after a full soccer season. A total of 48 female high school soccer athletes (age
      range: 14.00-17.97 years) were included in the study. These athletes were
      assigned to the non-collar group (n = 21) or to the collar group (n = 27). All
      athletes undewent MRI at both pre-season and post-season. In each session, a fMRI
      verbal N-Back task was used to engage working memory. A significant pre- to post
      season increase in fMRI blood oxygen level dependent (BOLD) signal was
      demonstrated when performing the N-back working memory task in the non-collar
      group but not in the collar group, despite the comparable exposure to head
      impacts during the season between the two groups. The collar group demonstrated
      significantly smaller pre- to post-season change in fMRI BOLD signal than the non
      collar group, suggesting a potential protective effect from the collar device.
      Significant correlations were also found between the pre- to post-season increase
      in fMRI brain activation and the decrease in task accuracy in the non-collar
      group, indicating an association between the compensatory mechanism in underlying
      neurophysiology and the alteration in the behavioral outcomes.

PMID- 29334836
TI  - SNF5 deficiency induces apoptosis resistance by repressing SATB1 expression in
      Sezary syndrome.
AB  - SNF5, is a core member of the SWI/SNF chromatin remodeling complex. It's
      deficiency leads to multiple types of aggressive cancer. Sezary syndrome, a
      leukemic variant of cutaneous T-cell lymphoma, is characterized by its resistance
      to apoptosis. Although the cause of apoptosis resistance is still poorly
      understood, recent evidence has revealed the importance of SATB1 in the apoptosis
      resistance of Sezary syndrome. In this study, we show that SNF5 is an upstream
      regulator of SATB1 in several conditions and that both are deficient in Sezary
      cells. Additionally, SNF5 not only controls the expression of SATB1, but also
      utilizes SATB1 to recruit itself to specific sites. Overexpression of SNF5
      induces SATB1 expression and partially reverse apoptosis resistance phenotype in
      Sezary cells. These results suggest that both SNF5 and SATB1 may regulate
      apoptosis-related genes in Sezary syndrome. Thus, targeting SWI/SNF complex may
      represent a promising approach for Sezary syndrome therapy.

PMID- 29334837
TI  - More expertise for a better perspective: Task and strategy-driven adaptive
      neurofunctional reorganization for word production in high-performing older
      adults.
AB  - The suggestion that neurofunctional reorganization may contribute to preserved
      language abilities is still emerging in aging studies. Some of these abilities,
      such as verbal fluency (VF), are not unitary but instead rely on different
      strategic processes that are differentially changed with age. Younger (n = 13)
      and older adults (n = 13) carried out an overt self-paced semantic and
      orthographic VF tasks within mixed fMRI design. Our results suggest that patterns
      of brain activation sustaining equivalent performances could be underpinned by
      different strategies facing brain changes during healthy aging. These main
      findings suggest that temporally mediated semantic clustering and frontally
      mediated orthographic switching were driven by evolutive neurofunctional
      resources in high-performing older adults. These age-related activation changes
      can appear to be compatible with the idea that unique neural patterns expressing
      distinctive cognitive strategies are necessary to support older adults'
      performance on VF tasks.

PMID- 29334838
TI  - Monitoring of leukemia stem cells in chronic myeloid leukemia patients.

PMID- 29334839
TI  - Bax inhibitor-1 is required for resisting the Early Brain Injury induced by
      subarachnoid hemorrhage through regulating IRE1-JNK pathway.
AB  - Background and Purpose Bax inhibitor-1 (BI-1) has been identified as a suppressor
      of Bax-mediated cell apoptosis by regulation of endoplasmic reticulum stress
      induced cell death. However, the role of BI-1 in Early Brain Injury (EBI) after
      subarachnoid hemorrhage (SAH) remains unclear. In the present study, we aim to
      explore the neuroprotective functions of BI-1 in EBI after SAH by using models of
      SAH that induced endovascular perforation in rats. Method The neurological score,
      brain water content and blood-brain barrier (BBB) permeability were evaluated
      simultaneously as prognostic indicators. Western blot, RT-PCR and TUNEL staining
      were performed to study the role and mechanisms of BI-1 in EBI after SAH. Results
      We found that BI-1 knockdown increased histological injury and the percentages of
      TUNEL-positive neuron in hippocampal, promoted the expressions of endoplasmic
      reticulum (ER) stress proteins inositol-requiring enzyme 1alpha (IRE1alpha) and
      TNF receptor-associated factor 2 (TRAF2), and increased the activation levels of
      apoptosis signal-regulating kinase 1 (ASK1) and c-Jun N-terminal kinase (JNK) in
      the hippocampus of SAH rats compared with rats in SAH + vehicle group. Conclusion
      Our results indicate that BI-1 may participate in the regulation of EBI after SAH
      by regulating IRE1-JNK pathway. Thus, the results suggest that BI-1 may be a
      potential therapeutic target for SAH treatment.

PMID- 29334840
TI  - Transcallosal conduction in paroxysmal kinesigenic dyskinesia.
AB  - OBJECTIVES: Detecting whether a possible disequilibrium between the excitatory
      and inhibitory interhemispheric interactions in paroxysmal kinesigenic dyskinesia
      (PKD) exists. METHODS: This study assessed measures of motor threshold, motor
      evoked potential latency, the cortical silent period, the ipsilateral silent
      period and the transcallosal conduction time (TCT) in PKD patients. Data were
      compared between the clinically affected hemisphere (aH) and the fellow
      hemisphere (fH). RESULTS: The transcallosal conduction time from the aH to the fH
      was 11.8 ms (range = 2.3-20.7) and 13.6 ms (range = 2.8-67.7) from the fH to the
      aH. The difference in TCT in the affected side was significant (p = .019).
      CONCLUSION: The findings demonstrated that, although inhibitory interneurons act
      normally and symmetrically between the motor cortices and transcallosal
      inhibition was normal and symmetrical between both sides, the onset of
      transcallosal inhibition was asymmetrical. The affected hemisphere's inhibition
      toward the unaffected hemisphere is faster compared to the inhibition provided by
      the fellow hemisphere. These results are consistent with an inhibitory deficit in
      the level of interhemispheric interactions. SIGNIFICANCE: This study revealed a
      defect in inhibition of the motor axis could be responsible in the pathological
      mechanisms of kinesigenic dyskinesia.

PMID- 29334841
TI  - Tocilizumab in the treatment of myocardial infarction.
AB  - Tocilizumab (TCZ) is an important biologic response modifier that rheumatologists
      routinely employ in the treatment of several systemic autoimmune diseases. TCZ
      binds to interleukin (IL)-6 receptors, inhibits cellular activation, and
      mitigates inflammation by IL-6. In mid-2017, TCZ was approved by the US Food and
      Drug Administration for its first nonrheumatologic condition, the treatment of
      chimeric antigen receptor (CAR) T cell-induced severe or life-threatening
      cytokine release syndrome in patients 2 years of age or older. With this approval
      and with the increasing use of TCZ off-label for other non-rheumatologic
      conditions such as Castleman's Disease and its variant TAFRO syndrome, where else
      might TCZ be successfully utilized as treatment? Recently interesting data has
      been published regarding possible use of TCZ in the treatment of myocardial
      infarction. This review focuses on the role of IL-6 and its receptor in
      myocardial inflammation and association with adverse clinical outcomes. Discussed
      are one animal study and two human trials that have been published studying the
      effect of TCZ in patients with acute myocardial infarction. Finally, this review
      summarizes the current data and makes recommendations for future clinical trial
      development in what hopefully will be a promising application of TCZ for a
      serious nonrheumatologic condition.

PMID- 29334843
TI  - High genetic diversity and low-population differentiation in the Patagonian sprat
      (Sprattus fuegensis) based on mitochondrial DNA.
AB  - The Patagonian sprat, Sprattus fuegensis, is a small pelagic marine fish that
      inhabits the continental shelf along the coasts of Chilean Patagonian and
      Argentina, a distribution that was highly impacted during the Last Glacial
      Maximum (LGM). In order to identify how the LGM played a role on the current
      observed genetic diversity and population structure of S. fuegensis, we analyzed
      1438 nucleotide positions from the control region of 335 individuals collected at
      12 sites across its distribution. Genetic diversity and differentiation indices
      were calculated to identify population structure, and a Bayesian skyride plot
      (BSRP) reconstruction was carried out to infer the historic population dynamics.
      Extremely high genetic diversity was found at all locations analyzed, non
      population structure was found across its distribution, and the BSRP showed two
      increases in effective population size over time. Our outcomes suggest that the
      current genetic diversity, population structure and population expansion may have
      occurred during the medium and late Pleistocene.

PMID- 29334842
TI  - A comprehensive review of endoscopic ultrasound core biopsy needles.
AB  - INTRODUCTION: Endoscopic ultrasound (EUS)-guided tissue acquisition by-fine
      needle biopsy (EUS-FNB) developed over the last two decades as an attempt to
      overcome the limitations of fine needle aspiration (FNA). There are now three
      commercially available second-generation FNB needles with different tip designs.
      Areas covered: In this review the roles of EUS-FNA and FNB, the history and
      evolution of the EUS core biopsy needle are addressed followed by a presentation
      of currently available needles. Literature search was conducted using MEDLINE,
      Controlled Trials Register, US Patent Registry, Google Scholar, and Conference
      Abstracts. Expert commentary: While FNA remains the reference standard, it is
      limited by the inability to retain stroma and associated cellular architecture in
      biopsy samples. Histologic architecture is of paramount importance in providing a
      molecular diagnosis and for accurate tumor staging. FNB offers a superior
      diagnostic yield to FNA and initial experiences with the three commercially
      available second-generation FNB needles show highly promising results.

PMID- 29334844
TI  - The molecular signature of AML with increased ALDH activity suggests a stem cell
      origin.
AB  - Enrichment of leukemic blasts with a stem cell phenotype correlates with poor
      survival in acute myeloid leukemia (AML). In this context, measurement of the
      stem cell marker aldehyde-dehydrogenase (ALDH) activity can distinguish poor
      prognosis cases with increased fractions of ALDH-positive cells (ALDH-numerous
      AML) and favorable outcome cases with low percentages (ALDH-rare AML). It has
      been shown that ALDH-numerous AML favor leukemic engraftment in
      xenotransplantation assays which suggests increased leukemic stem cell (LSC)
      potential. To test if this reflects an immature cell of origin, comparative gene
      expression studies of CD34+ leukemic blasts were performed. This analysis
      revealed increased expression of LSC and HSC signatures in ALDH-numerous AML,
      whereas ALDH-rare AML were enriched for a progenitor signature. The enrichment of
      stemness-associated transcriptional programs suggests that ALDH-numerous AML
      derive from immature hematopoietic progenitors and offers an explanation for the
      poor prognosis and therapy resistance of this subgroup which is likely caused by
      inherited stem cell properties.

PMID- 29334845
TI  - Neutrophil-to-lymphocyte ratio and mural nodule height as predictive factors for
      malignant intraductal papillary mucinous neoplasms.
AB  - BACKGROUND: Accurate preoperative prediction for malignant IPMN is still
      challenging. The aim of this study was to investigate the validity of neutrophil
      to-lymphocyte ratio (NLR) and mural nodule height (MNH) for predicting malignant
      intraductal papillary mucinous neoplasm (IPMN). METHODS: The medical records of
      60 patients who underwent pancreatectomy for IPMN were retrospectively reviewed.
      RESULTS: NLR tended to be higher in malignant IPMN (median: 2.23) than in benign
      IPMN (median: 2.04; p = .14). MNH was significantly greater in malignant IPMN
      (median: 16 mm) than in benign IPMN (median: 8 mm; p < .01). The optimal cutoff
      values for the NLR and MNH were 3.60 and 11 mm, respectively. The sensitivity and
      specificity of NLR >=3.60 for predicting malignant IPMN were 40% and 93%, and
      those of MNH >=11 mm were 73% and 77%, respectively. Univariate analysis revealed
      that NLR >=3.60 (p < .01) and MNH >=11 mm (p < .01) were significant predictive
      factors. On multivariate analysis, enhanced solid component was identified as an
      independent factor, but NLR >=3.60 and MNH >=11 mm were not. CONCLUSIONS: NLR and
      MNH are suboptimal tests in predicting malignant IPMN; however, they can be
      useful to assist in clinical decision-making.

PMID- 29334846
TI  - Scapular motion adaptations in junior overhead athletes: a three-dimensional
      kinematic analysis in tennis players and non-overhead athletes.
AB  - Adult overhead athletes without a history of shoulder injury show scapular
      adaptations. There is a lack of detailed assessment of scapular kinematics in
      junior overhead athletes. This study aims to investigate three-dimensional
      scapular kinematics in junior overhead athletes. We recruited a total of 20
      junior tennis players and 20 healthy children without participation in any
      overhead sports in this study. Bilateral scapular kinematic data were recorded
      using an electromagnetic tracking device for scapular plane glenohumeral
      elevation. The data were further analysed at 30 degrees , 45 degrees , 60 degrees
      , 90 degrees  and 120 degrees  during glenohumeral elevation and lowering.
      Statistical comparisons of the data between groups (junior overhead athletes and
      non-overhead athletes) and sides (serve dominant and non-dominant shoulders of
      the overhead athletes) were analysed with the ANOVA. Comparisons showed that, in
      general, the scapula was more upwardly rotated and anteriorly tilted in overhead
      athletes when compared to non-overhead athletes, however there was no side-to
      side differences when serve dominant and non-dominant shoulders compared in
      junior overhead athletes. The serve dominant arm of junior overhead athletes had
      alternations in scapular kinematics when compared with the non-overhead athletes.
      These findings provide clinical evaluation implications and the need for
      clinicians to assess for potential adaptations in junior overhead athletes.

PMID- 29334847
TI  - Patient and family psychoeducation: Service development and implementation in a
      center in Iran.
AB  - BACKGROUND: Family and patient psychoeducation have demonstrated significant
      improvement in clinical and social outcomes for patients suffering from severe
      mental disorders and their families. However, these evidence-based practices are
      not widely implemented at service delivery level and into routine clinical
      practice, especially in less developed countries. AIM: The aim of this article is
      to report the processes of development and implementation of a psychoeducational
      service for patients with severe mental illnesses and their families in Iran.
      METHOD: The program was developed at Roozbeh Hospital in Tehran, Iran. A group of
      clinicians worked on the development phase of the program and drafting the
      manuals. Then, a series of workshops and supervision sessions were held to train
      group leaders for implementation of the group psychoeducation for patients and
      families. In the pilot phase, the services were delivered to two groups of
      patients and families, and then the manual was revised based on the feedback from
      group leaders and participants. RESULTS: The program consisted of eight 90-minute
      weekly patient group sessions and 6 weekly multiple family group sessions. Two
      manuals for patient education (schizophrenia and bipolar disorder) were
      developed. Several information sheets were developed and distributed during
      different sessions of family and patient psychoeducation related to the content
      of each session. Despite providing the hospital clinicians with the information
      regarding these new services, less than 10% of the admitted patients were
      referred by their clinicians. CONCLUSION: Feasibility and sustainability of the
      program are affected by a number of factors. Low referral rate of clinicians,
      limited resources of the hospital, issues related to stigma and logistic issues
      are barriers in implementation of these services. Administrators' and clinicians'
      understanding of the importance of patient and family psychoeducation seems to be
      crucial in sustainability of such programs in routine service delivery.

PMID- 29334848
TI  - The effect of social support, gratitude, resilience and satisfaction with life on
      depressive symptoms among police officers following Hurricane Katrina.
AB  - BACKGROUND: Police officers in the New Orleans geographic area faced a number of
      challenges following Hurricane Katrina. AIM: This cross-sectional study examined
      the effect of social support, gratitude, resilience and satisfaction with life on
      symptoms of depression. METHOD: A total of 86 male and 30 female police officers
      from Louisiana participated in this study. Ordinary least-square (OLS) regression
      mediation analysis was used to estimate direct and indirect effects between
      social support, gratitude, resilience, satisfaction with life and symptoms of
      depression. All models were adjusted for age, alcohol intake, military experience
      and an increase in the number of sick days since Hurricane Katrina. RESULTS: Mean
      depressive symptom scores were 9.6 +/- 9.1 for females and 10.9 +/- 9.6 for
      males. Mediation analyses indicates that social support and gratitude are
      directly associated with fewer symptoms of depression. Social support also
      mediated the relationships between gratitude and depression, gratitude and
      satisfaction with life, and satisfaction with life and depression. Similarly,
      resilience mediated the relationship between social support and fewer symptoms of
      depression. CONCLUSION: Social support, gratitude and resilience are associated
      with higher satisfaction with life and fewer symptoms of depression. Targeting
      and building these factors may improve an officer's ability to address symptoms
      of depression.

PMID- 29334849
TI  - How to implement an enhanced recovery programme after colorectal surgery?
AB  - INTRODUCTION: Although the concept of enhanced recovery after surgery was
      introduced more than 20 years ago, its implementation in daily practice still
      remains difficult. RESULTS: This article addresses bottlenecks and barriers to
      the development of enhanced recovery programme (ERP). Barriers to the
      implementation are multifactorial and are raised by the different actors of these
      programmes: surgeons, anaesthetists, nurses, patients. Solutions and steps that
      must be respected to succeed in introducing ERP in an hospital are proposed.
      CONCLUSIONS: Large-scale implementation of ERP continues to face mainly lack of
      trust and communication. Solutions exist and are based particularly on team work
      and interdisciplinary collaboration.

PMID- 29334850
TI  - An Immunopathological Evaluation of the Porcine Cholecyst Matrix as a Muscle
      Repair Graft in a Male Rat Abdominal Wall Defect Model.
AB  - With the increasing use of animal-based biomaterials for regenerative medical
      applications, the need for their safety assessment is paramount. A porcine
      cholecyst-derived scaffold (CDS), intended as a muscle repair graft, prepared by
      a nondetergent/enzymatic method was engrafted in a rat abdominal wall defect
      model. Host tissue-scaffold interface samples were collected 2, 8, and 16 weeks
      postimplantation and evaluated by histopathology, immunohistochemistry, and
      electron microscopy. The nature of the tissue reaction was compared with those
      induced by a jejunum-derived scaffold (JDS) prepared by the same method and a
      commercial-grade small intestinal submucosa (CSIS) scaffold. A study of the
      immunopathological response in major lymphoid tissues and immunophenotyping for
      M1 and M2 macrophages was performed at the host tissue-scaffold interface.
      Further, "irritancy scores" for CDS and JDS were determined using CSIS as the
      reference material. Both CDS and JDS appeared to be potential biomaterials for
      muscle grafts, but the former stimulated a skeletal muscle tissue remodeling
      response predominated by M2 macrophages. The data support the notion that
      biomaterials with similar biocompatibility, based on local tissue response on
      implantation, may cause differential immunogenicity. Additionally, CDS compared
      to JDS and CSIS was found to be less immunotoxic.

PMID- 29334851
TI  - What Are the Psychosocial Factors Associated With Migraine in the Child? Comorbid
      Psychiatric Disorders, Family Functioning, Parenting Style, or Mom's Psychiatric
      Symptoms?
AB  - OBJECTIVE: Psychiatric diagnoses, parenting style, family functioning among
      children and adolescents with migraine, and psychiatric symptoms of their mothers
      were examined. METHODS: The K-SADS and other measurements were used to assess
      psychiatric disorders in 50 children with migraine (aged 8-18) and matched 50
      controls. RESULTS: At least one psychiatric disorder was diagnosed in 56% of the
      migraine group. The presence of any psychiatric disorder in children (odds ratio
      [OR] = 2.765, P = .027) and somatization symptoms in their mothers (OR = 2.061, P
      = .025) were increasing the risk of migraine diagnosis. The parenting style scale
      assessments revealed that parents in the migraine group grant their children less
      autonomy. CONCLUSION: Psychiatric comorbidity, especially depression and anxiety
      disorders, is more common in children with migraine. The frequency of eating
      disorder is also higher. Evaluating comorbidity, family functioning, and
      particularly affective responsiveness in migraine families may guide the
      clinician to a targeted treatment plan.

PMID- 29334852
TI  - Child Neurology: A Fragile Future.

PMID- 29334853
TI  - Therapeutic Plasma Exchange Use in Pediatric Neurologic Disorders at a Tertiary
      Care Center: A 10-Year Review.
AB  - Pediatric neurologic conditions requiring therapeutic plasma exchange are rare in
      children and literature is sparse. The study aims to determine the outcomes,
      safety, and feasibility of therapeutic plasma exchange treatment in pediatric
      neurologic disorders. This retrospective analysis looked at the outcomes and
      safety of therapeutic plasma exchange in children (n = 50) with neurologic
      conditions. Patient age ranged <1 to 19 years old with a mean of 10.35 years. Of
      the 50 children treated with plasmapheresis, 26 patients received inpatient
      rehabilitation. At discharge, functional status can be summarized as follows: 24
      (48%) with mental status impairment, 10 (20%) with vision impairment, 19 (38%)
      with bladder incontinence, and 37 (74%) with motor impairment. Three-month follow
      up: 30% with mental status impairment, 10% with vision impairment, 18% with
      bladder incontinence, and 52% with motor impairment. Therapeutic plasma exchange
      is an effective and safe therapy for neurological conditions in the pediatric
      population.

PMID- 29334854
TI  - The Association Between Premorbid Conditions in School-Aged Children With
      Prolonged Concussion Recovery.
AB  - The association between preexisting anxiety, depression, and/or
      neurodevelopmental disorders and symptom duration among younger children who
      sustain concussions is not well known. The authors conducted a prospective cohort
      study of 569 patients presenting to a pediatric neurology clinic with the
      diagnosis of concussion. The authors measured associations between symptom
      duration and premorbid conditions, as well as gender, age, mechanism of injury,
      and other factors. Premorbid conditions were common in both age groups. On
      univariate modeling female gender, age >12 years, and premorbid conditions were
      associated with longer symptom duration. On multivariable modeling, females and
      patients <=12 years old with a history of headaches, migraines, or a history of
      psychiatric conditions took significantly longer to recover than those without
      such conditions. Premorbid conditions are associated with a prolonged recovery
      from concussion among those patients <=12 years old.

PMID- 29334856
TI  - Stroke After Minor Head Trauma in Infants and Young Children With Basal Ganglia
      Calcification: A Lenticulostriate Vasculopathy?
AB  - The authors retrospectively reviewed charts of the children with basal ganglia
      stroke who either had preceding minor head injury or showed basal ganglia
      calcification on computed tomography (CT) scan. Twenty children, 14 boys and 6
      girls were identified. Eighteen were aged between 7 months to 17 months.
      Presentation was with hemiparesis in 17 and seizures in 3. Preceding minor head
      trauma was noted in 18. Family history was positive in 1 case. Bilateral basal
      ganglia calcification on CT scan was noted in 18. Brain magnetic resonance
      imaging done in 18 infants showed acute or chronic infarcts in basal ganglia.
      Results of other laboratory and radiological investigations were normal. Four
      infants were lost to follow-up, 9 achieved complete or nearly completely
      recovery, and 7 had persistent neurological deficits. Basal ganglia calcification
      likely represents mineralized lenticulostriate arteries, a marker of
      lenticulostriate vasculopathy. Abnormal lenticulostriate vessels are vulnerable
      to injury and thrombosis after minor head trauma resulting in stroke.

PMID- 29334857
TI  - Association of Neutrophil/Lymphocyte Ratio With Intravenous Immunoglobulin
      Treatment in Children With Guillain-Barre Syndrome.
AB  - Guillain-Barre syndrome (GBS) is an acute immune-mediated inflammatory
      polyneuropathy of the peripheral nervous system. The authors aimed to investigate
      whether the neutrophil/lymphocyte (N/L) and platelet/lymphocyte (P/L) ratios are
      the parameters that associated with the drug treatment or severity of GBS. Twenty
      seven children with GBS were retrospectively analyzed from the medical records of
      patients who attended to the Pediatric Neurology Department of the Gaziantep
      University Hospital. Biochemical and hematologic parameters were measured.
      Leukocytes, neutrophils counts and N/L ratio were significantly higher before the
      intravenous immunoglobulin treatment ( P < .001). However, there were no marked
      differences in platelet count and P/L ratio. In addition, marked correlation was
      observed between the N/L ratio after treatment and duration of weakness. The
      results of the study showed that N/L ratio is significantly higher in GBS
      patients, and reduces following with intravenous immunoglobulin treatment.

PMID- 29334858
TI  - Case study of occupational mercury exposure during decontamination of turnaround
      in refinery plant.
AB  - Decontamination during turnaround (TA) can lead to high exposure to toxic
      chemicals among workers. The decontamination process in refinery plants usually
      comprises two types, i.e. steam and chemical decontamination. No matter the
      method used, concentrations of toxic chemicals must be measured using the direct
      reading instrument at the end of each decontamination cycle, which maybe repeated
      several times until the readings are in acceptable level. To evaluate mercury
      exposure of decontamination workers during decontamination procedure in
      comprehensive turnaround of a refinery plant. Thirty personal and 16 area air
      samples were collected using passive dosimeters and absorbent tubes,
      respectively, during 8 days of the decontamination in comprehensive turnaround.
      All samples were analyzed using inductively coupled plasma mass spectrometry (ICP
      MS). Good practices and standard procedures for air sampling and analysis were
      performed. The TWA concentrations were calculated and compared between steam and
      chemical decontamination workers. All area samples were well below TLV (ND -
      0.0016 mg/m3) while 5 of 14 samples collected at the steam team and 1 of 16
      samples taken from the chemical team exceeded the TLV. The geometric mean (GSD)
      of TWA concentration of the steam team was 0.0057(10.4906) mg/m3, which is about
      twice as high as that of the chemical team, 0.0031(6.9422) mg/m3. The highest
      mercury concentration, 0.1037 mg/m3, was collected from a steam decontamination
      worker. According to the activities and observation, the steam team may have high
      exposure while reading the chemical concentrations at the end of the
      decontamination cycle.

PMID- 29334859
TI  - Bayesian analysis of semi-parametric Cox models with latent variables.
AB  - Respiratory cancer is one of the most commonly diagnosed cancers as well as the
      leading cause of cancer death. Numerous efforts have been devoted to reducing the
      death rate of respiratory cancer. In this article, we propose a semi-parametric
      Cox model with latent variables to assess the effects of observed and latent risk
      factors on survival time of respiratory cancer. The characteristics of latent
      risk factors are characterized via multiple observed indicators by a confirmatory
      factor analysis model. We develop a Bayesian estimation procedure to obtain the
      estimates of parameters. Simulation shows that the performance of the proposed
      methodology is satisfactory. The proposed method is applied to analyze the
      Surveillance, Epidemiology, and End Results Program data set.

PMID- 29334860
TI  - A mixed-effects, spatially varying coefficients model with application to multi
      resolution functional magnetic resonance imaging data.
AB  - Spatial resolution plays an important role in functional magnetic resonance
      imaging studies as the signal-to-noise ratio increases linearly with voxel
      volume. In scientific studies, where functional magnetic resonance imaging is
      widely used, the standard spatial resolution typically used is relatively low
      which ensures a relatively high signal-to-noise ratio. However, for pre-surgical
      functional magnetic resonance imaging analysis, where spatial accuracy is
      paramount, high-resolution functional magnetic resonance imaging may play an
      important role with its greater spatial resolution. High spatial resolution comes
      at the cost of a smaller signal-to-noise ratio. This begs the question as to
      whether we can leverage the higher signal-to-noise ratio of a standard functional
      magnetic resonance imaging study with the greater spatial accuracy of a high
      resolution functional magnetic resonance imaging study in a pre-operative
      patient. To answer this question, we propose to regress the statistic image from
      a high resolution scan onto the statistic image obtained from a standard
      resolution scan using a mixed-effects model with spatially varying coefficients.
      We evaluate our model via simulation studies and we compare its performance with
      a recently proposed model that operates at a single spatial resolution. We apply
      and compare the two models on data from a patient awaiting tumor resection. Both
      simulation study results and the real data analysis demonstrate that our newly
      proposed model indeed leverages the larger signal-to-noise ratio of the standard
      spatial resolution scan while maintaining the advantages of the high spatial
      resolution scan.

PMID- 29334862
TI  - The effects of an unanticipated side-cut on lower extremity kinematics and ground
      reaction forces during a drop landing.
AB  - Unanticipated direction to cut after landing may alter the lower extremity
      landing biomechanics when performing landing motions. These alterations may
      potentially increase the risk of ACL injury. The purpose of this study was to
      determine if an unanticipated side-cut affects lower extremity landing
      biomechanics in females. Eighteen recreational female athletes participated in
      two blocks of testing: the first block of testing consisted of three acceptable
      trials of anticipated dominant limb and non-dominant limb 45-degree diagonal
      cutting after landing, which were performed in a counterbalanced order. The
      second block of testing consisted of three acceptable trials of unanticipated
      dominant limb and non-dominant limb diagonal cutting after landing. Data analysis
      mainly focused on the dominant limb landing biomechanics. Unanticipated side-cut
      landing, compared (paired t-test, p < 0.05) to the anticipated landings, resulted
      in less hip abduction and tibial internal rotation angle at initial contact (IC)
      and a lower maximum ankle inversion angle and a greater maximum knee abduction
      angle, and knee and hip displacement. Also, greater posterior GRF and a longer
      time to peak medial GRF were exhibited. These outcomes indicate that athletes may
      adapt their landing mechanics to land unsafely when encountering an unanticipated
      event.

PMID- 29334861
TI  - COPD management by Swedish general practitioners - baseline results of the
      PRIMAIR study.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a common cause of
      suffering and death. Evidence-based management of COPD by general practitioners
      (GPs) is crucial for decreasing the impact of the disease. Efficient strategies
      include early diagnosis, smoking cessation and multimodal treatment. AIM: To
      describe knowledge about and skills for managing COPD in GPs in Sweden. METHODS:
      Prior to COPD education (the PRIMAIR Study), GPs at primary health care centers
      (PHCCs) in Stockholm replied to 13 written, patient-case based, multiple choice
      and free-text questions about COPD. Their knowledge and practical management
      skills were assessed by assigned points that were analyzed with non-parametric
      tests. RESULTS: Overall, 250 GPs at 34 PHCCs replied (89% response rate). Total
      mean score was 9.9 (maximum 26). Scores were highest on 'management of smoking
      cessation', 'follow-up after exacerbation' and 'diagnostic procedures'.
      Spirometry was used frequently, although interpretation skills were suboptimal.
      'Management of maintenance therapy', 'management of multimorbidity' and
      'interprofessional cooperation' had mediocre scores. Scores were unrelated to
      whether there was a nurse-led asthma/COPD clinic at the PHCC. CONCLUSIONS:
      Swedish GPs' knowledge of COPD and adherence to current guidelines seem
      insufficient. A nurse-led asthma/COPD clinic at the PHCC does not correlate with
      sufficient COPD skills in the GPs. The relevance of this study to participants'
      actual clinical practice and usefulness of easy-to-access clinical guides are
      interesting topics for future investigation. To identify problem areas, we
      suggest using questionnaires prior to educational interventions. Key Points
      General practitioners (GPs) play a crucial role in providing evidence-based care
      for patients with chronic obstructive pulmonary disease (COPD) who are treated in
      primary care. Swedish GPs' knowledge about COPD and adherence to current
      guidelines seem insufficient. Areas in greatest need of improvement are
      spirometry interpretation, management of maintenance therapy, management of
      multimorbidity in patients with COPD and interprofessional cooperation.

PMID- 29334863
TI  - Totally Percutaneous Fenestration via the "Cheese-Wire" Technique to Facilitate
      Endovascular Aneurysm Repair in Chronic Aortic Dissection.
AB  - Here, we describe a totally percutaneous technique for longitudinal fenestration
      of a chronic dissection flap in the setting of endovascular aneurysm repair
      (EVAR), where the septum would otherwise preclude proper endograft sealing. This
      technique is demonstrated in a 65-year-old man with a history of open surgical
      repair of a Stanford type A aortic dissection, with a type B component that was
      managed nonoperatively. The patient developed aneurysmal degeneration of the
      infrarenal aorta during follow-up, and his anatomy was well suited for EVAR with
      the exception of a chronic dissection flap dividing the proximal seal zone. Using
      bilateral percutaneous access, a wire was passed through an existing fenestration
      in the septum from true to false lumen and snared from the contralateral side.
      Downward traction on this through-wire was then used as a "cheese-wire" to divide
      the septum longitudinally and clear it from the proximal fixation site. Removal
      of the septum provided an adequate proximal seal zone for the endograft, and
      standard infrarenal EVAR was then performed with a good technical result.
      Longitudinal fenestration using this technique is a useful adjunctive maneuver to
      facilitate EVAR in the setting of chronic aortic dissection and is safely
      achievable via a totally percutaneous approach.

PMID- 29334864
TI  - Pain Assessment Documentation After Opioid Administration at a Community Teaching
      Hospital.
AB  - PURPOSE: To compare pain assessment documentation postopioid administration in
      hospitalized patients before and after implementing nurse education. METHODS:
      Patients 18 years and older were randomly selected for inclusion if they received
      1 opioid dose while admitted to the hospital. Through retrospective chart review,
      opioid data, including date and time, were collected for each opioid
      administered. Pain score data, including time and date of documentation, were
      recorded for analysis. The primary objective of this study was to determine
      whether a nursing education intervention would improve documentation of pain
      scores within an appropriate time frame postadministration of an opioid
      medication. The intervention was a training presentation uploaded to the
      institution's intranet with an assessment. The primary outcome was measured by
      comparing the frequency by which nurses documented pain scores following opioid
      administration before and after education. RESULTS: Three hundred twenty patients
      (160 patients per time period) were evaluated. The percentage of pain scores
      recorded within the appropriate assessment time following opioid administration
      increased from 32.9% to 37.8% ( P = .003). The proportion of appropriate pain
      score documentation increased 4.9% (95% confidence interval [CI]: 1.6%-8.2%).
      CONCLUSION: An increase in the documentation of efficacy assessments after opioid
      administration was demonstrated after nursing education. Further studies should
      be done to identify additional strategies to increase monitoring as well as to
      identify a benchmark for institutions with regard to pain management monitoring.

PMID- 29334865
TI  - "I Never Would Have Caught That Before": Pharmacist Perceptions of Using Clinical
      Decision Support for Antimicrobial Stewardship in the United States.
AB  - To systematically improve the appropriateness of antibiotic prescribing,
      antimicrobial stewardship programs have been developed. There is a paucity of
      literature examining how pharmacists perform antimicrobial stewardship using a
      clinical decision support system in a hospital setting. The purpose of this
      qualitative study was to develop a model exploring how pharmacists perform
      antimicrobial stewardship to identify areas for programmatic improvement.
      Semistructured interviews were conducted across a health care system until
      saturation of themes was reached. Pharmacists identified that self-efficacy and
      time were vital for antimicrobial stewardship to be performed, while culture of
      the hospital and attitude facilitated the process of stewardship. Antimicrobial
      stewardship programs using clinical decision support tools should ensure
      pharmacists have adequate time to address rules, provide easy-to-use resources
      and training to support self-efficacy, and engage influential physicians to
      support a culture of collaboration.

PMID- 29334866
TI  - Follow-up of an age-period-cohort analysis on alcohol-related mortality trends in
      Sweden 1970-2015 with predictions to 2025.
AB  - BACKGROUND AND AIMS: Several studies have indicated that birth cohorts are
      important in explaining trends in alcohol-related mortality. An earlier study
      from Sweden with data up to 2002 showed that birth cohorts that grew up under
      periods of more liberal alcohol policies had higher alcohol-related mortality
      than those cohorts growing up under more restrictive time periods. In spite of
      increasing alcohol consumption, predictions in 2002 also indicated lower alcohol
      related mortality in the future. The aim of this study is to follow-up whether
      the effects of birth cohorts and the predictions made for Sweden still holds
      using data up to 2015. METHOD: The study comprised an age-period-cohort analysis
      and predictions based on population predictions from Statistics Sweden. The
      analysis was based on all alcohol-related deaths in the Swedish population
      between 1969 and 2015 for the cohorts born in the decades 1920 through 1990. Data
      were restricted to people 15-84 years of age. In total, the analysis covered
      68,341 deaths and more than 284 million person-years. RESULTS: Male and female
      cohorts born in the 1940s to 1950s exhibited the highest alcohol-related
      mortality, while those born in the 1970s continued to have the lowest alcohol
      related mortality rates. The predicted mortality rates for males are still
      anticipated to decrease somewhat through 2025. CONCLUSIONS: The updated age
      period-cohort analysis further supports the importance of focusing on restrictive
      alcohol policies targeting adolescents.

PMID- 29334867
TI  - Increasing prevalence of emotional symptoms in higher socioeconomic strata: Trend
      study among Danish schoolchildren 1991-2014.
AB  - AIMS: The aims of this study were: (a) to examine trends in daily emotional
      symptoms among 11- to 15-year-olds from 1991 to 2014 in Denmark, and (b) to
      examine trends in social inequality in daily emotional symptoms, that is, whether
      the differences in prevalence between adolescents with parents of varying
      occupational social class changed over time. METHODS: We combined seven
      comparable cross-sectional Health Behaviour in School-aged Children surveys (
      N=31,169). Daily emotional symptoms were measured by the HBSC Symptom Check List
      and occupational social class (OSC) by students' reports about parents'
      occupation. We calculated absolute (per cent) differences in emotional symptoms
      between high and low OSC and relative differences by odds ratio for emotional
      symptoms by parents' OSC. RESULTS: Eight per cent reported at least one daily
      emotional symptoms, with an increasing trend from 1991 to 2014 ( p<0.001). The
      prevalence in high, middle and low OSC was 6.2%, 7.4% and 10.6% ( p<0.0001). From
      1991 to 2014, there was an increase in the prevalence of daily emotional symptoms
      in high ( p<0.0001) and middle ( p<0.0001) but not low OSC ( p=0.4404). This
      resulted in a diminishing absolute social inequality in emotional symptoms. The
      statistical interaction between OSC and survey year was significant ( p=0.0023)
      and suggests a diminishing relative social inequality in emotional symptoms from
      1991 to 2014. CONCLUSIONS: There was an increasing prevalence of daily emotional
      symptoms from 1991 to 2014 and a diminishing social inequality in prevalence of
      daily emotional symptoms in terms of both absolute and relative social
      inequality.

PMID- 29334868
TI  - Biomechanical analyses of synchronised swimming standard and contra-standard
      sculling.
AB  - Synchronised swimming involves a variety of sculling movements essential for body
      support and propulsion but its study is scarce. We aimed to biomechanically
      compare standard and contra-standard sculling techniques, and to observe the
      relationship between measures. Six synchronised swimmers performed two, 30 s
      maximal intensity, fully tethered standard and contra-standard sculling motions.
      Kinetic and kinematic data were obtained using a load-cell and underwater
      cameras, respectively. Force decreased along both techniques' bouts, but no
      differences in-between techniques were noted for any kinetic variables. Standard
      sculling presented a higher cycle rate and a lower elbow mean angle than the
      contra-standard sculling (2.4 +/- 0.3 vs. 2.0 +/- 0.2 cycles/s and 134.1 +/- 5.8
      and 141.5 +/- 4.7 degrees , p < 0.05). In the standard sculling, by removing and
      maintaining the variation between participants (rw and r, respectively), the
      absolute mean force was directly related with cycle rate (rw = 0.60) and wrist
      angular velocity during flexion (r = 0.82), while in the contra-standard
      condition the force was inversely associated with wrist mean angle (r = -0.95)
      and directly with hand speed (rw = 0.76), and elbow angular velocity (rw ~ 0.60).
      Therefore, technique learning and training require different attention by coaches
      and swimmers.

PMID- 29334869
TI  - The influence of water depth on kinematic and spatiotemporal gait parameters
      during aquatic treadmill walking.
AB  - The purpose of this study was to investigate kinematic and spatiotemporal
      variables of aquatic treadmill walking at three different water depths. A total
      of 15 healthy individuals completed three two-minute walking trials at three
      different water depths. The aquatic treadmill walking was conducted at waist
      depth, chest-depth and neck-depth, while a customised 3-D underwater motion
      analysis system captured their walking. Each participant's self-selected walking
      speed at the waist level was used as a reference speed, which was applied to the
      remaining two test conditions. A repeated measures ANOVA showed statistically
      significant differences among the three walking conditions in stride length,
      cadence, peak hip extension, hip range of motion (ROM), peak ankle plantar
      flexion and ankle ROM (All p values < 0.05). The participants walked with
      increased stride length and decreased cadence during neck level as compared to
      waist and chest level. They also showed increased ankle ROM and decreased hip ROM
      as the water depth rose from waist and chest to the neck level. However, our
      study found no significant difference between waist and chest level water in all
      variables. Hydrodynamics, such as buoyancy and drag force, in response to changes
      in water depths, can affect gait patterns during aquatic treadmill walking.

PMID- 29334870
TI  - Images in Vascular Medicine. Linear morphea masquerading as superficial
      thrombophlebitis.

PMID- 29334871
TI  - Biomonitoring of arsenic in woodworkers exposed to CCA and evaluation of other
      non-occupational sources in Uruguay.
AB  - In Uruguay wood-impregnation plants use chromated copper arsenate (CCA) as
      preservative applying good manufacture practices (GMP). This study aims a
      retrospective evaluation of toxicologically relevant species levels in CCA
      exposed woodworker's urine (As-U) and an assessment of the effects of work risk
      factors and non-occupational sources in As-U of workers from a selected plant.
      From 2014 to 2016, As-U in 212 urine samples (As-U) of 73 woodworkers from six
      CCA impregnation plants were determined. In one of these plants, 35 workers were
      interviewed to obtain individual data of work tasks, lifestyles, diet, habits,
      etc. that may contribute to their overall exposure to Arsenic. Responses were
      statistically evaluated. Out of the 212 urine samples from 73 woodworkers, 96%
      showed lower levels of As-U than those established by health regulations (<35MUgL
      1). According to their work tasks 34% of 35 surveyed workers showed high exposure
      risk to As and 29% moderate exposure risk. Although they have lower levels of As
      U owing to their personal protective equipment, As-U significantly correlate to
      work risk factors. Consumption of bottled water could also contribute to As-U
      levels as a non-occupational source. These results confirm that efforts of
      Uruguayan authorities to promote GMP were successful and justify the importance
      and frequency of As-U systematic biomonitoring for occupational risk assessment.
      A significant accomplishment of this work is that non-occupational sources of As
      like bottled water consumption should also be considered in future studies.

PMID- 29334872
TI  - Labelling as reference Centre of GRACE (Groupe francophone de Rehabilitation
      Amelioree apres ChirurgiE) for colorectal surgery: its impact on the
      implementation of enhanced recovery programme at the University Hospital of
      Liege.
AB  - BACKGROUND: Enhanced recovery programme (ERP) has been used in our hospital since
      2005 for selected colorectal surgeries. Since October 2015, after labelling as
      GRACE reference centre, we included all patients scheduled for elective
      colorectal surgery in this programme. We assessed the impact of our labelling on
      the implementation of ERP. METHODS: Results of our first 100 patients entered in
      the GRACE database were analyzed: length of stay, complications, readmission,
      adherence to the protocol. These results are compared to those of the last 100
      patients undergoing colorectal surgery before our labelling. RESULTS: Patients'
      characteristics in both groups were similar. The complications rate was similar
      in both groups. The global length of hospital stay was 4 [5] days vs. 8.5 [8]
      (median [IQR]), respectively after and before labelling; p < .001. The duration
      of hospitalization for the different subgroups (age, surgical approach, types of
      surgery) were significantly shorter after our labelling (respectively: p < .001,
      p < .01, and p < .05). CONCLUSIONS: Our results demonstrate that labelling as
      reference centre increases the efficiency of the implementation of ERP. The fact
      that all subgroups of patients benefit from ERP must encourage inclusion of all
      patients undergoing elective colorectal surgery in ERP.

PMID- 29334873
TI  - Nobiletin prevents cadmium-induced neuronal apoptosis by inhibiting reactive
      oxygen species and modulating JNK/ERK1/2 and Akt/mTOR networks in rats.
AB  - Objectives Cadmium (Cd), an extremely noxious environmental pollutant is known to
      induce oxidative stress leading to neurodegenerative diseases. Nobiletin, a
      citrus flavonoid is reported to possess various pharmacological properties. This
      study investigates the effects of nobiletin over Cd-induced neuronal apoptosis in
      rodent experimental model. Methods To separate group of male Sprague Dawley rats,
      Cd (2 mL/kg/day) was subcutaneously injected for one month which results in a
      dose level of 1 mg/kg Cd. Couple of days prior to Cd injection, the treatment
      group rats regularly received nobiletin (50, 100, or 200 mg/kg b.wt) orally
      through the study period. Results Cd-induced ROS levels and malondialdehyde (MDA)
      content were inhibited by nobiletin and improved glutathione levels. Nobiletin
      reduced neuronal apoptosis induced by Cd and raised cleaved caspase-3 levels.
      Intriguingly, nobiletin blocked JNK and Erk1/2 phosphorylation and down-regulated
      the pathways. Raised expression of kinases - MKK and ASK1 were reduced by
      nobiletin. Discussion The suppressed expression of phosphatases - PP2A and PP5
      were up-regulated on nobiletin treatment. Nobiletin significantly blocked the
      activation of Akt/mTOR signaling. Enhanced phosphorylation of S6K1, Akt, and 4E
      BP1 induced by Cd was significantly inhibited by nobiletin. The raised levels of
      raptor and rictor proteins were remarkably down-regulated on nobiletin treatment.
      Collectively, the observations of this study indicate protective effects of
      nobiletin against Cd-induced neurotoxicity.

PMID- 29334874
TI  - A Comparison of Collaborative Care Outcomes in Two Health Care Systems: VA
      Clinics and Federally Qualified Health Centers.
AB  - OBJECTIVE: Collaborative care for depression results in symptom reduction when
      compared with usual care. No studies have systematically compared collaborative
      care outcomes between veterans treated at Veterans Affairs (VA) clinics and
      civilians treated at publicly funded federally qualified health centers (FQHCs)
      after controlling for demographic and clinical characteristics. METHODS: Data
      from two randomized controlled trials that used a similar collaborative care
      intervention for depression were combined to conduct post hoc analyses (N=759).
      The Telemedicine-Enhanced Antidepressant Management intervention was delivered in
      VA community-based outpatient clinics (CBOCs), and the Outreach Using
      Telemedicine for Rural Enhanced Access in Community Health intervention was
      delivered in FQHCs. Multivariate logistic regression was used to determine
      whether veteran status moderated the effect of the intervention on treatment
      response (>50% reduction in symptoms). RESULTS: There was a significant main
      effect for intervention (odds ratio [OR]=5.23, p<.001) and a moderating effect
      for veteran status, with lower response rates among veterans compared with
      civilians (OR=.21, p=.01). The addition of variables representing medication
      dosage and number of mental health and general health appointments did not
      influence the moderating effect. A sensitivity analysis stratified by gender
      found a significant moderating effect of veteran status for men but not women.
      CONCLUSIONS: Veteran status was a significant moderator of collaborative care
      effectiveness for depression, indicating that veterans receiving collaborative
      care at a CBOC are at risk of nonresponse. Unmeasured patient- or system-level
      characteristics may contribute to poorer response among veterans.

PMID- 29334875
TI  - Summary of Key Issues Raised in the Technology for Early Awareness of Addiction
      and Mental Illness (TEAAM-I) Meeting.
AB  - Technology provides an unparalleled opportunity to remove barriers to earlier
      identification and engagement in services for mental and addictive disorders by
      reaching people earlier in the course of illness and providing links to just-in
      time, cost-effective interventions. Achieving this opportunity, however, requires
      stakeholders to challenge underlying assumptions about traditional pathways to
      mental health care. In this Open Forum, the authors highlight key issues
      discussed in the Technology for Early Awareness of Addiction and Mental Illness
      (TEAAM-I) meeting-held October 13-14, 2016, in New York City-that are related to
      three identified areas in which technology provides important and unique
      opportunities to advance early identification, increase service engagement, and
      decrease the duration of untreated mental and addictive disorders.

PMID- 29334877
TI  - Utilization of Mental Health Services by Children Displaced by Hurricane Katrina.
AB  - OBJECTIVE: This study examined changes in utilization of mental health services
      after Hurricane Katrina among children with preexisting conditions who were
      displaced from their homes in Louisiana disaster counties and resettled in Texas.
      METHODS: A retrospective analysis was performed on Medicaid claims data for
      101,950 children from 2004 to 2006. Pre-post changes in utilization of mental
      health services by the displaced children and three control groups were compared.
      The control groups were children from Louisiana disaster counties who were not
      displaced, Louisiana children from nondisaster counties, and Texas children
      enrolled in Medicaid. RESULTS: The proportion of children who had a prescription
      fill for psychotropic medication and the average days' supply per child decreased
      in each group, but the decreases were significantly larger for the displaced
      group than for the control groups. The decreases in both measures were largest
      for stimulants and antidepressants, the two most common medication classes. By
      contrast, changes in the proportion of children with an encounter involving
      psychiatric services and the average number of psychiatric services encounters
      per child did not vary systematically across the displaced and control groups.
      CONCLUSIONS: The contrast between the results for medication utilization and
      encounters reveals a potential gap in post-Katrina provision of care. Although
      the findings for encounters indicate that, on average, displaced children did not
      experience a disruption in provider visits, the medication estimates suggest that
      they often did not obtain pharmaceutical treatment. Future disaster responses may
      be improved by addressing logistical impediments faced by disaster victims in
      filling their prescriptions for psychiatric medications.

PMID- 29334876
TI  - Three Nontraditional Approaches to Improving the Capacity, Accessibility, and
      Quality of Mental Health Services: An Overview.
AB  - To provide evidence for wider use of peer workers and other nonprofessionals, the
      authors examined three approaches to mental health service provision-peer support
      worker (PSW) programs, task shifting, and mental health first-aid and community
      advocacy organizations-summarizing their effectiveness, identifying similarities
      and differences, and highlighting opportunities for integration. Relevant
      articles obtained from PubMed, MEDLINE, and Google Scholar searches are
      discussed. Studies indicate that PSWs can achieve outcomes equal to or better
      than those achieved by nonpeer mental health professionals. PSWs can be
      particularly effective in reducing hospital admissions and inpatient days and
      engaging severely ill patients. When certain care tasks are given to individuals
      with less training than professionals (task shifting), these staff members can
      provide psychoeducation, engage service users in treatment, and help them achieve
      symptom reduction and manage risk of relapse. Mental health first-aid and
      community organizations can reduce stigma, increase awareness of mental health
      issues, and encourage help seeking. Most PSW programs have reported
      implementation challenges, whereas such challenges are fewer in task-shifting
      programs and minimal in mental health first-aid. Despite challenges in scaling
      and integrating these approaches into larger systems, they hold promise for
      improving access to and quality of care. Research is needed on how these
      approaches can be combined to expand a community's capacity to provide care.
      Because of the serious shortage of mental health providers globally and the
      rising prevalence of mental illness, utilizing nontraditional providers may be
      the only solution in both low- and high-resource settings, at least in the short
      term.

PMID- 29334878
TI  - The Use of Standardized Discharge in IPS Supported Employment Programs.
AB  - OBJECTIVE: Some researchers have argued for using standardized discharge rules in
      individual placement and support (IPS) based on time of unemployment. To evaluate
      potential adverse outcomes of these rules, the authors examined time to first job
      over 24 months in a large randomized controlled study. METHODS: This secondary
      analysis of 2,055 participants in the Mental Health Treatment Study, using
      bootstrapping and survival analysis, estimated and compared the likelihood of
      finding a first job in the IPS and control groups during each quarter over 24
      months. RESULTS: Although the likelihood of obtaining a first job declined over
      time, IPS recipients were more likely than participants in a control group to
      find first jobs for at least 18 months. CONCLUSIONS: Use of standardized
      discharge rules in IPS, based on initial periods of unemployment, may be cost
      effective but would penalize recipients who respond more slowly. Natural
      attrition may be a more sensitive and ethical way to create capacity.

PMID- 29334879
TI  - The Extent to Which Psychiatrists Diagnose and Treat Substance Use Disorders.

PMID- 29334880
TI  - Variability in Clinical Outcomes for Youths Treated for Subthreshold Severe
      Mental Disorders at an Early Intervention Service.
AB  - OBJECTIVE: The study assessed the longitudinal clinical and functional outcomes
      of young people receiving early intervention services for subthreshold
      manifestations of severe mental disorders at a youth mental health service in
      Sydney, Australia. METHODS: The six-month, prospective, longitudinal study
      collected data on clinical outcomes of 243 young people treated for subsyndromal
      presentations of putative major mental disorders. Reliable change index scores
      and effect sizes were calculated to compare results at baseline, three months,
      and six months for measures of symptoms (Brief Psychiatric Rating Scale [BPRS]),
      psychological distress (Kessler 10 [K10]), and social functioning (Social and
      Occupational Functioning Assessment Scale [SOFAS]). RESULTS: There was
      variability in outcomes across each of the outcome measures, with 25%, 33%, and
      23% of patients showing reliable improvement and 9%, 13%, and 5% showing reliable
      deterioration for the SOFAS, K10, and BPRS, respectively. Many individuals did
      not show linear improvement or deterioration, with reliable change within
      individuals varying significantly between the zero- to three-month and three- to
      six-month time points. After the analyses were controlled for covariates,
      baseline severity or impairment and number of sessions with a psychiatrist or
      psychologist contributed a small (4%-8%) but significant amount to the total
      variance in outcomes at six months. CONCLUSIONS: Most individuals did not show
      significant deterioration, and about one in four showed reliable improvement by
      six months. However, individual patterns of change were diverse, highlighting the
      importance of further research into factors that influence treatment outcomes
      among youths with subthreshold presentations of severe mental disorders.

PMID- 29334881
TI  - A Proactive Behavioral Health Service Model to Address Use of Constant
      Observation in a General Hospital.
AB  - In hospitals, use of constant observation (CO) causes significant economic burden
      without demonstrated reduction in adverse events. A novel quality improvement
      (QI) project was developed to reduce use of CO by integrating proactive
      behavioral health management of all patients requiring CO in a general hospital.
      Specific nonpharmacologic and pharmacologic interventions used in this project,
      which included 491 patients, are discussed. Data collected were compared with
      data from a baseline period before project implementation. The average monthly
      cost of observers was reduced by 33%, and length of stay was reduced 15% without
      increased complications. Using QI to develop proactive and consistent involvement
      of a designated behavioral health team and potentially reproducible care
      protocols for patients requiring CO resulted in improvement in quality, reduction
      in cost, and enhanced behavioral health integration in the general hospital.

PMID- 29334882
TI  - Federal Parity and Access to Behavioral Health Care in Private Health Plans.
AB  - OBJECTIVE: The 2008 Mental Health Parity and Addiction Equity Act (MHPAEA) sought
      to improve access to behavioral health care by regulating health plans' coverage
      and management of services. Health plans have some discretion in how to achieve
      compliance with MHPAEA, leaving questions about its likely effects on health plan
      policies. In this study, the authors' objective was to determine how private
      health plans' coverage and management of behavioral health treatment changed
      after the federal parity law's full implementation. METHODS: A nationally
      representative survey of commercial health plans was conducted in 60 market areas
      across the continental United States, achieving response rates of 89% in 2010
      (weighted N=8,431) and 80% in 2014 (weighted N=6,974). Senior executives at
      responding plans were interviewed regarding behavioral health services in each
      year and (in 2014) regarding changes. Student's t tests were used to examine
      changes in services covered, cost-sharing, and prior authorization requirements
      for both behavioral health and general medical care. RESULTS: In 2014, 68% of
      insurance products reported having expanded behavioral health coverage since
      2010. Exclusion of eating disorder coverage was eliminated between 2010 (23%) and
      2014 (0%). However, more products reported excluding autism treatment in 2014
      (24%) than 2010 (8%). Most plans reported no change to prior-authorization
      requirements between 2010 and 2014. CONCLUSIONS: Implementation of federal parity
      legislation appears to have been accompanied by continuing improvement in
      behavioral health coverage. The authors did not find evidence of widespread
      noncompliance or of unintended effects, such as dropping coverage of behavioral
      health care altogether.

PMID- 29334883
TI  - Renal outcomes in patients initiated on tenofovir disoproxil fumarate-based
      antiretroviral therapy at a community health centre in Malawi.
AB  - Tenofovir-based antiretroviral therapy (TDF ART) is the first-line regimen for
      human immunodeficiency virus (HIV) in Africa. However, contemporary data on
      nephrotoxicity are lacking. We determined the renal outcomes of patients
      commenced on TDF ART in Malawi. ART-naive patients initiated on TDF ART at a
      community health centre between 1 July 2013 and 31 December 2015 were included.
      The estimated glomerular filtration rate (eGFR, Cockcroft-Gault) was recorded at
      the initiation of therapy and over 18 months thereafter. The prevalence of renal
      impairment at ART initiation (eGFR < 60 ml/min) and the incidence of
      nephrotoxicity (eGFR < 50 ml/min) were determined. A total of 439 patients
      (median age: 32 years; 317 [72.2%] female) were included. Twenty-one (4.8%)
      patients had renal impairment at ART initiation; eGFR improved in all during
      follow-up. Nephrotoxicity occurred in 17 (4.0%) patients with eGFR > 50 ml/min at
      baseline, predominantly within the first six months of therapy. Increasing age
      and diastolic hypertension (>100 mmHg) were independent risk factors for
      nephrotoxicity development. The prevalence of kidney disease at ART initiation
      was 4.8% and nephrotoxicity occurred in 4.0%. Some eGFR decline may have been due
      to weight gain. Targeted monitoring of kidney function six months after TDF
      initiation should be considered in Malawi.

PMID- 29334884
TI  - Acroangiodermatitis mimicking Kaposi's sarcoma in an HIV-positive man.
AB  - Kaposi's sarcoma (KS) is the commonest human immunodeficiency virus (HIV)-related
      malignancy with its characteristic cutaneous morphological appearance and
      histopathological features. However, it can be simulated by other co-morbid
      opportunistic infections and unrelated dermatological conditions. We describe
      such a case of acroangiodermatitis in an HIV co-infected man, based on exclusion
      of KS histologically and the absence of human herpesvirus 8, the causative agent
      of KS.

PMID- 29334885
TI  - 2016 United Kingdom national guideline on the sexual health care of men who have
      sex with men.
AB  - This guideline is intended for use in UK Genitourinary medicine clinics and
      sexual health services but is likely to be of relevance in all sexual health
      settings, including general practice and Contraception and Sexual Health (CASH)
      services, where men who have sex with men (MSM) seek sexual health care or where
      addressing the sexual health needs of MSM may have public health benefits. For
      the purposes of this document, MSM includes all gay, bisexual and all other males
      who have sex with other males and both cis and trans men. This document does not
      provide guidance on the treatment of particular conditions where this is covered
      in other British Association for Sexual Health and HIV (BASHH) Guidelines but
      outlines best practice in multiple aspects of the sexual health care of MSM.
      Where prevention of sexually transmitted infections including HIV can be
      addressed as an integral part of clinical care, this is consistent with the
      concept of combination prevention and is included. The document is designed
      primarily to provide guidance on the direct clinical care of MSM but also makes
      reference to the design and delivery of services with the aim of supporting
      clinicians and commissioners in providing effective services. Methodology This
      document was produced in accordance with the guidance set out in the BASHH CEG's
      document 'Framework for guideline development and assessment' published in 2010
      at http://www.bashh.org/guidelines and with reference to the Agree II instrument.
      Following the production of the updated framework in April 2015, the GRADE system
      for assessing evidence was adopted and the draft recommendations were regraded.
      Search strategy (see also Appendix 1) Ovid Medline 1946 to December 2014, Medline
      daily update, Embase 1974 to December 2014, Pubmed NeLH Guidelines Database,
      Cochrane library from 2000 to December 2014. Search language English only. The
      search for Section 3 was conducted on PubMed to December 2014. Priority was given
      to peer-reviewed papers published in scientific journals, although for many
      issues evidence includes conference abstracts listed on the Embase database. In
      addition, for 'Identification of problematic recreational drug and alcohol use'
      section and 'Sexual problems and dysfunctions in MSM' section, searches included
      PsycINFO. Methods Article titles and abstracts were reviewed and if relevant the
      full text article was obtained. Priority was given to randomised controlled trial
      and systematic review evidence, and recommendations made and graded on the basis
      of best available evidence. Piloting and feedback The first draft of the
      guideline was circulated to the writing group and to a small group of relevant
      experts, third sector partners and patient representatives who were invited to
      comment on the whole document and specifically on particular sections. The
      revised draft was reviewed by the CEG and then reviewed by the BASHH
      patient/public panel and posted on the BASHH website for public consultation. The
      final draft was piloted before publication. Guideline update The guidelines will
      be reviewed and revised in five years' time, 2022.

PMID- 29334886
TI  - Factors associated with recent unsuppressed viral load in HIV-1-infected patients
      in care on first-line antiretroviral therapy in South Africa.
AB  - Unsuppressed viral load (VL) in patients on antiretroviral therapy (ART) occurs
      when treatment fails to suppress a person's VL and is associated with decreased
      survival and increased HIV transmission. The objective of this study was to
      evaluate factors associated with unsuppressed VL (VL > 400 copies/ml) in patients
      currently in care on first-line ART for >= 6 months attending South African
      public healthcare facilities. We analysed electronic medical records of ART
      patients with a VL result on record who started ART between January 2004 and
      April 2016 from 271 public health facilities. We present descriptive and
      multivariable logistic regression for unsuppressed VL at last visit using a
      priori variables. We included 244,370 patients (69% female) on first-line ART in
      April 2016 for >= 6 months. Median age at ART start was 33 years (7% were < 15
      years old). Median duration on ART was 3.7 years. Adjusting for other variables,
      factors associated with having an unsuppressed VL at the most recent visit among
      patients in care included: (1) < 15 years old at ART start (adjusted odds ratio
      [aOR]=2.58; 95% CI = 2.37, 2.81) versus 15-49 years at ART start, (2) male gender
      (aOR = 1.29; 95% CI = 1.25, 1.35), (3) 6-12 months on ART versus longer (aOR =
      1.34; 95% CI = 1.29, 1.40), (4) on tuberculosis (TB) treatment (aOR = 1.78; 95%
      CI = 1.48, 2.13), and (5) prior ART exposure versus none (aOR = 1.20; 95% CI =
      1.08, 1.32). Approximately 85% of the ART cohort who were in care had achieved
      viral suppression, though men, youth/adolescents, patients with prior ART
      exposure, those with short duration of ART, and patients on TB treatment had
      increased odds of not achieving viral suppression. There is a need to develop and
      evaluate targeted interventions for ART patients in care who are at high risk of
      unsuppressed VL.

PMID- 29334887
TI  - Bi-objective integer programming for RNA secondary structure prediction with
      pseudoknots.
AB  - BACKGROUND: RNA structure prediction is an important field in bioinformatics, and
      numerous methods and tools have been proposed. Pseudoknots are specific motifs of
      RNA secondary structures that are difficult to predict. Almost all existing
      methods are based on a single model and return one solution, often missing the
      real structure. An alternative approach would be to combine different models and
      return a (small) set of solutions, maximizing its quality and diversity in order
      to increase the probability that it contains the real structure. RESULTS: We
      propose here an original method for predicting RNA secondary structures with
      pseudoknots, based on integer programming. We developed a generic bi-objective
      integer programming algorithm allowing to return optimal and sub-optimal
      solutions optimizing simultaneously two models. This algorithm was then applied
      to the combination of two known models of RNA secondary structure prediction,
      namely MEA and MFE. The resulting tool, called BiokoP, is compared with the other
      methods in the literature. The results show that the best solution (structure
      with the highest F1-score) is, in most cases, given by BiokoP. Moreover, the
      results of BiokoP are homogeneous, regardless of the pseudoknot type or the
      presence or not of pseudoknots. Indeed, the F1-scores are always higher than 70%
      for any number of solutions returned. CONCLUSION: The results obtained by BiokoP
      show that combining the MEA and the MFE models, as well as returning several
      optimal and several sub-optimal solutions, allow to improve the prediction of
      secondary structures. One perspective of our work is to combine better mono
      criterion models, in particular to combine a model based on the comparative
      approach with the MEA and the MFE models. This leads to develop in the future a
      new multi-objective algorithm to combine more than two models. BiokoP is
      available on the EvryRNA platform: https://EvryRNA.ibisc.univ-evry.fr .

PMID- 29334888
TI  - diceR: an R package for class discovery using an ensemble driven approach.
AB  - BACKGROUND: Given a set of features, researchers are often interested in
      partitioning objects into homogeneous clusters. In health research, cancer
      research in particular, high-throughput data is collected with the aim of
      segmenting patients into sub-populations to aid in disease diagnosis, prognosis
      or response to therapy. Cluster analysis, a class of unsupervised learning
      techniques, is often used for class discovery. Cluster analysis suffers from some
      limitations, including the need to select up-front the algorithm to be used as
      well as the number of clusters to generate, in addition, there may exist several
      groupings consistent with the data, making it very difficult to validate a final
      solution. Ensemble clustering is a technique used to mitigate these limitations
      and facilitate the generalization and reproducibility of findings in new cohorts
      of patients. RESULTS: We introduce diceR (diverse cluster ensemble in R), a
      software package available on CRAN: https://CRAN.R-project.org/package=diceR
      CONCLUSIONS: diceR is designed to provide a set of tools to guide researchers
      through a general cluster analysis process that relies on minimizing subjective
      decision-making. Although developed in a biological context, the tools in diceR
      are data-agnostic and thus can be applied in different contexts.

PMID- 29334889
TI  - Protein-protein interface hot spots prediction based on a hybrid feature
      selection strategy.
AB  - BACKGROUND: Hot spots are interface residues that contribute most binding
      affinity to protein-protein interaction. A compact and relevant feature subset is
      important for building machine learning methods to predict hot spots on protein
      protein interfaces. Although different methods have been used to detect the
      relevant feature subset from a variety of features related to interface residues,
      it is still a challenge to detect the optimal feature subset for building the
      final model. RESULTS: In this study, three different feature selection methods
      were compared to propose a new hybrid feature selection strategy. This new
      strategy was proved to effectively reduce the feature space when we were building
      the prediction models for identifying hotspot residues. It was tested on eighty
      two features, both conventional and newly proposed. According to the strategy,
      combining the feature subsets selected by decision tree and mRMR (maximum
      Relevance Minimum Redundancy) individually, we were able to build a model with 6
      features by using a PSFS (Pseudo Sequential Forward Selection) process. Compared
      with other state-of-art methods for the independent test set, our model had shown
      better or comparable predictive performances (with F-measure 0.622 and recall
      0.821). Analysis of the 6 features confirmed that our newly proposed feature
      CNSV_REL1 was important for our model. The analysis also showed that the
      complementarity between features should be considered as an important aspect when
      conducting the feature selection. CONCLUSION: In this study, most important of
      all, a new strategy for feature selection was proposed and proved to be effective
      in selecting the optimal feature subset for building prediction models, which can
      be used to predict hot spot residues on protein-protein interfaces. Moreover, two
      aspects, the generalization of the single feature and the complementarity between
      features, were proved to be of great importance and should be considered in
      feature selection methods. Finally, our newly proposed feature CNSV_REL1 had been
      proved an alternative and effective feature in predicting hot spots by our study.
      Our model is available for users through a webserver:
      http://zhulab.ahu.edu.cn/iPPHOT/ .

PMID- 29334891
TI  - Tuning iteration space slicing based tiled multi-core code implementing
      Nussinov's RNA folding.
AB  - BACKGROUND: RNA folding is an ongoing compute-intensive task of bioinformatics.
      Parallelization and improving code locality for this kind of algorithms is one of
      the most relevant areas in computational biology. Fortunately, RNA secondary
      structure approaches, such as Nussinov's recurrence, involve mathematical
      operations over affine control loops whose iteration space can be represented by
      the polyhedral model. This allows us to apply powerful polyhedral compilation
      techniques based on the transitive closure of dependence graphs to generate
      parallel tiled code implementing Nussinov's RNA folding. Such techniques are
      within the iteration space slicing framework - the transitive dependences are
      applied to the statement instances of interest to produce valid tiles. The main
      problem at generating parallel tiled code is defining a proper tile size and tile
      dimension which impact parallelism degree and code locality. RESULTS: To choose
      the best tile size and tile dimension, we first construct parallel parametric
      tiled code (parameters are variables defining tile size). With this purpose, we
      first generate two nonparametric tiled codes with different fixed tile sizes but
      with the same code structure and then derive a general affine model, which
      describes all integer factors available in expressions of those codes. Using this
      model and known integer factors present in the mentioned expressions (they define
      the left-hand side of the model), we find unknown integers in this model for each
      integer factor available in the same fixed tiled code position and replace in
      this code expressions, including integer factors, with those including
      parameters. Then we use this parallel parametric tiled code to implement the well
      known tile size selection (TSS) technique, which allows us to discover in a given
      search space the best tile size and tile dimension maximizing target code
      performance. CONCLUSIONS: For a given search space, the presented approach allows
      us to choose the best tile size and tile dimension in parallel tiled code
      implementing Nussinov's RNA folding. Experimental results, received on modern
      Intel multi-core processors, demonstrate that this code outperforms known closely
      related implementations when the length of RNA strands is bigger than 2500.

PMID- 29334890
TI  - Characterization of the late embryogenesis abundant (LEA) proteins family and
      their role in drought stress tolerance in upland cotton.
AB  - BACKGROUND: Late embryogenesis abundant (LEA) proteins are large groups of
      hydrophilic proteins with major role in drought and other abiotic stresses
      tolerance in plants. In-depth study and characterization of LEA protein families
      have been carried out in other plants, but not in upland cotton. The main aim of
      this research work was to characterize the late embryogenesis abundant (LEA)
      protein families and to carry out gene expression analysis to determine their
      potential role in drought stress tolerance in upland cotton. Increased cotton
      production in the face of declining precipitation and availability of fresh water
      for agriculture use is the focus for breeders, cotton being the backbone of
      textile industries and a cash crop for many countries globally. RESULTS: In this
      work, a total of 242, 136 and 142 LEA genes were identified in G. hirsutum, G.
      arboreum and G. raimondii respectively. The identified genes were classified into
      eight groups based on their conserved domain and phylogenetic tree analysis. LEA
      2 were the most abundant, this could be attributed to their hydrophobic
      character. Upland cotton LEA genes have fewer introns and are distributed in all
      chromosomes. Majority of the duplicated LEA genes were segmental. Syntenic
      analysis showed that greater percentages of LEA genes are conserved. Segmental
      gene duplication played a key role in the expansion of LEA genes. Sixty three
      miRNAs were found to target 89 genes, such as miR164, ghr-miR394 among others.
      Gene ontology analysis revealed that LEA genes are involved in desiccation and
      defense responses. Almost all the LEA genes in their promoters contained ABRE,
      MBS, W-Box and TAC-elements, functionally known to be involved in drought stress
      and other stress responses. Majority of the LEA genes were involved in secretory
      pathways. Expression profile analysis indicated that most of the LEA genes were
      highly expressed in drought tolerant cultivars Gossypium tomentosum as opposed to
      drought susceptible, G. hirsutum. The tolerant genotypes have a greater ability
      to modulate genes under drought stress than the more susceptible upland cotton
      cultivars. CONCLUSION: The finding provides comprehensive information on LEA
      genes in upland cotton, G. hirsutum and possible function in plants under drought
      stress.

PMID- 29334892
TI  - The genome of a prasinoviruses-related freshwater virus reveals unusual diversity
      of phycodnaviruses.
AB  - BACKGROUND: Phycodnaviruses are widespread algae-infecting large dsDNA viruses
      and presently contain six genera: Chlorovirus, Prasinovirus, Prymnesiovirus,
      Phaeovirus, Coccolithovirus and Raphidovirus. The members in Prasinovirus are
      identified as marine viruses due to their marine algal hosts, while prasinovirus
      freshwater relatives remain rarely reported. RESULTS: Here we present the
      complete genomic sequence of a novel phycodnavirus, Dishui Lake Phycodnavirus 1
      (DSLPV1), which was assembled from Dishui Lake metagenomic datasets. DSLPV1
      harbors a linear genome of 181,035 bp in length (G + C content: 52.7%), with 227
      predicted genes and 2 tRNA encoding regions. Both comparative genomic and
      phylogenetic analyses indicate that the freshwater algal virus DSLPV1 is closely
      related to the members in Prasinovirus, a group of marine algae infecting
      viruses. In addition, a complete eukaryotic histone H3 variant was identified in
      the genome of DSLPV1, which is firstly detected in phycodnaviruses and
      contributes to understand the interaction between algal virus and its eukaryotic
      hosts. CONCLUSION: It is in a freshwater ecosystem that a novel Prasinovirus
      related viral complete genomic sequence is discovered, which sheds new light on
      the evolution and diversity of the algae infecting Phycodnaviridae.

PMID- 29334893
TI  - High-sensitivity HLA typing by Saturated Tiling Capture Sequencing (STC-Seq).
AB  - BACKGROUND: Highly polymorphic human leukocyte antigen (HLA) genes are
      responsible for fine-tuning the adaptive immune system. High-resolution HLA
      typing is important for the treatment of autoimmune and infectious diseases.
      Additionally, it is routinely performed for identifying matched donors in
      transplantation medicine. Although many HLA typing approaches have been
      developed, the complexity, low-efficiency and high-cost of current HLA-typing
      assays limit their application in population-based high-throughput HLA typing for
      donors, which is required for creating large-scale databases for transplantation
      and precision medicine. RESULTS: Here, we present a cost-efficient Saturated
      Tiling Capture Sequencing (STC-Seq) approach to capturing 14 HLA class I and II
      genes. The highly efficient capture (an approximately 23,000-fold enrichment) of
      these genes allows for simplified allele calling. Tests on five genes (HLA
      A/B/C/DRB1/DQB1) from 31 human samples and 351 datasets using STC-Seq showed
      results that were 98% consistent with the known two sets of digitals (field1 and
      field2) genotypes. Additionally, STC can capture genomic DNA fragments longer
      than 3 kb from HLA loci, making the library compatible with the third-generation
      sequencing. CONCLUSIONS: STC-Seq is a highly accurate and cost-efficient method
      for HLA typing which can be used to facilitate the establishment of population
      based HLA databases for the precision and transplantation medicine.

PMID- 29334894
TI  - Rare variant association analysis in case-parents studies by allowing for missing
      parental genotypes.
AB  - BACKGROUND: The development of next-generation sequencing technologies has
      facilitated the identification of rare variants. Family-based design is commonly
      used to effectively control for population admixture and substructure, which is
      more prominent for rare variants. Case-parents studies, as typical strategies in
      family-based design, are widely used in rare variant-disease association
      analysis. Current methods in case-parents studies are based on complete case
      parents data; however, parental genotypes may be missing in case-parents trios,
      and removing these data may lead to a loss in statistical power. The present
      study focuses on testing for rare variant-disease association in case-parents
      study by allowing for missing parental genotypes. RESULTS: In this report, we
      extended the collapsing method for rare variant association analysis in case
      parents studies to allow for missing parental genotypes, and investigated the
      performance of two methods by using the difference of genotypes between affected
      offspring and their corresponding "complements" in case-parent trios and TDT
      framework. Using simulations, we showed that, compared with the methods just only
      using complete case-parents data, the proposed strategy allowing for missing
      parental genotypes, or even adding unrelated affected individuals, can greatly
      improve the statistical power and meanwhile is not affected by population
      stratification. CONCLUSIONS: We conclude that adding case-parents data with
      missing parental genotypes to complete case-parents data set can greatly improve
      the power of our strategy for rare variant-disease association.

PMID- 29334895
TI  - Challenges imposed by minor reference alleles on the identification and reporting
      of clinical variants from exome data.
AB  - BACKGROUND: The conventional variant calling of pathogenic alleles in exome and
      genome sequencing requires the presence of the non-pathogenic alleles as genome
      references. This hinders the correct identification of variants with minor and/or
      pathogenic reference alleles warranting additional approaches for variant
      calling. RESULTS: More than 26,000 Exome Aggregation Consortium (ExAC) variants
      have a minor reference allele including variants with known ClinVar disease
      alleles. For instance, in a number of variants related to clotting disorders, the
      phenotype-associated allele is a human genome reference allele (rs6025, rs6003,
      rs1799983, and rs2227564 using the assembly hg19). We highlighted how the current
      variant calling standards miss homozygous reference disease variants in these
      sites and provided a bioinformatic panel that can be used to screen these
      variants using commonly available variant callers. We present exome sequencing
      results from an individual with venous thrombosis to emphasize how pathogenic
      alleles in clinically relevant variants escape variant calling while non
      pathogenic alleles are detected. CONCLUSIONS: This article highlights the
      importance of specialized variant calling strategies in clinical variants with
      minor reference alleles especially in the context of personal genomes and exomes.
      We provide here a simple strategy to screen potential disease-causing variants
      when present in homozygous reference state.

PMID- 29334896
TI  - Global analysis of prokaryotic tRNA-derived cyclodipeptide biosynthesis.
AB  - BACKGROUND: Among naturally occurring small molecules, tRNA-derived
      cyclodipeptides are a class that have attracted attention for their diverse and
      desirable biological activities. However, no tools are available to link
      cyclodipeptide synthases identified within prokaryotic genome sequences to their
      chemical products. Consequently, it is unclear how many genetically encoded
      cyclodipeptides represent novel products, and which producing organisms should be
      targeted for discovery. RESULTS: We developed a pipeline for identification and
      classification of cyclodipeptide biosynthetic gene clusters and prediction of
      aminoacyl-tRNA substrates and complete chemical structures. We leveraged this
      tool to conduct a global analysis of tRNA-derived cyclodipeptide biosynthesis in
      93,107 prokaryotic genomes, and compared predicted cyclodipeptides to known
      cyclodipeptide synthase products and all known chemically characterized
      cyclodipeptides. By integrating predicted chemical structures and gene cluster
      architectures, we created a unified map of known and unknown genetically encoded
      cyclodipeptides. CONCLUSIONS: Our analysis suggests that sizeable regions of the
      chemical space encoded within sequenced prokaryotic genomes remain unexplored.
      Our map of the landscape of genetically encoded cyclodipeptides provides
      candidates for targeted discovery of novel compounds. The integration of our
      pipeline into a user-friendly web application provides a resource for further
      discovery of cyclodipeptides in newly sequenced prokaryotic genomes.

PMID- 29334898
TI  - seq-seq-pan: building a computational pan-genome data structure on whole genome
      alignment.
AB  - BACKGROUND: The increasing application of next generation sequencing technologies
      has led to the availability of thousands of reference genomes, often providing
      multiple genomes for the same or closely related species. The current approach to
      represent a species or a population with a single reference sequence and a set of
      variations cannot represent their full diversity and introduces bias towards the
      chosen reference. There is a need for the representation of multiple sequences in
      a composite way that is compatible with existing data sources for annotation and
      suitable for established sequence analysis methods. At the same time, this
      representation needs to be easily accessible and extendable to account for the
      constant change of available genomes. RESULTS: We introduce seq-seq-pan, a
      framework that provides methods for adding or removing new genomes from a set of
      aligned genomes and uses these to construct a whole genome alignment. Throughout
      the sequential workflow the alignment is optimized for generating a
      representative linear presentation of the aligned set of genomes, that enables
      its usage for annotation and in downstream analyses. CONCLUSIONS: By providing
      dynamic updates and optimized processing, our approach enables the usage of whole
      genome alignment in the field of pan-genomics. In addition, the sequential
      workflow can be used as a fast alternative to existing whole genome aligners for
      aligning closely related genomes. seq-seq-pan is freely available at
      https://gitlab.com/rki_bioinformatics.

PMID- 29334897
TI  - The genome sequence of the commercially cultivated mushroom Agrocybe aegerita
      reveals a conserved repertoire of fruiting-related genes and a versatile suite of
      biopolymer-degrading enzymes.
AB  - BACKGROUND: Agrocybe aegerita is an agaricomycete fungus with typical mushroom
      features, which is commercially cultivated for its culinary use. In nature, it is
      a saprotrophic or facultative pathogenic fungus causing a white-rot of hardwood
      in forests of warm and mild climate. The ease of cultivation and fructification
      on solidified media as well as its archetypal mushroom fruit body morphology
      render A. aegerita a well-suited model for investigating mushroom developmental
      biology. RESULTS: Here, the genome of the species is reported and analysed with
      respect to carbohydrate active genes and genes known to play a role during fruit
      body formation. In terms of fruit body development, our analyses revealed a
      conserved repertoire of fruiting-related genes, which corresponds well to the
      archetypal fruit body morphology of this mushroom. For some genes involved in
      fruit body formation, paralogisation was observed, but not all fruit body
      maturation-associated genes known from other agaricomycetes seem to be conserved
      in the genome sequence of A. aegerita. In terms of lytic enzymes, our analyses
      suggest a versatile arsenal of biopolymer-degrading enzymes that likely account
      for the flexible life style of this species. Regarding the amount of genes
      encoding CAZymes relevant for lignin degradation, A. aegerita shows more
      similarity to white-rot fungi than to litter decomposers, including 18 genes
      coding for unspecific peroxygenases and three dye-decolourising peroxidase genes
      expanding its lignocellulolytic machinery. CONCLUSIONS: The genome resource will
      be useful for developing strategies towards genetic manipulation of A. aegerita,
      which will subsequently allow functional genetics approaches to elucidate
      fundamentals of fruiting and vegetative growth including lignocellulolysis.

PMID- 29334899
TI  - Association between sequence variants in panicle development genes and the number
      of spikelets per panicle in rice.
AB  - BACKGROUND: Balancing panicle-related traits such as panicle length and the
      numbers of primary and secondary branches per panicle, is key to improving the
      number of spikelets per panicle in rice. Identifying genetic information
      contributes to a broader understanding of the roles of gene and provides
      candidate alleles for use as DNA markers. Discovering relations between panicle
      related traits and sequence variants allows opportunity for molecular application
      in rice breeding to improve the number of spikelets per panicle. RESULTS: In
      total, 142 polymorphic sites, which constructed 58 haplotypes, were detected in
      coding regions of ten panicle development gene and 35 sequence variants in six
      genes were significantly associated with panicle-related traits. Rice cultivars
      were clustered according to their sequence variant profiles. One of the four
      resultant clusters, which contained only indica and tong-il varieties, exhibited
      the largest average number of favorable alleles and highest average number of
      spikelets per panicle, suggesting that the favorable allele combination found in
      this cluster was beneficial in increasing the number of spikelets per panicle.
      CONCLUSIONS: Favorable alleles identified in this study can be used to develop
      functional markers for rice breeding programs. Furthermore, stacking several
      favorable alleles has the potential to substantially improve the number of
      spikelets per panicle in rice.

PMID- 29334900
TI  - Process evaluation of the RaDIANT community study: a dialysis facility-level
      intervention to increase referral for kidney transplantation.
AB  - BACKGROUND: The Reducing Disparities in Access to kidNey Transplantation
      Community Study (RaDIANT) was an End-Stage Renal Disease (ESRD) Network 6
      developed, dialysis facility-level randomized trial testing the effectiveness of
      a 1-year multicomponent education and quality improvement intervention in
      increasing referral for kidney transplant evaluation among selected Georgia
      dialysis facilities. METHODS: To assess implementation of the RaDIANT
      intervention, we conducted a process evaluation at the conclusion of the
      intervention period (January-December 2014). We administered a 20-item survey to
      the staff involved with transplant education in 67 dialysis facilities randomized
      to participate in intervention activities. Survey items assessed facility
      participation in the intervention (fidelity and reach), helpfulness and
      willingness to continue intervention activities (sustainability), suggestions for
      improving intervention components (sustainability), and factors that may have
      influenced participation and study outcomes (context). We defined high fidelity
      to the intervention as completing 11 or more activities, and high participation
      in an activity as having at least 75% participation across intervention
      facilities. RESULTS: Staff from 65 of the 67 dialysis facilities completed the
      questionnaire, and more than half (50.8%) reported high adherence (fidelity) to
      RaDIANT intervention requirements. Nearly two-thirds (63.1%) of facilities
      reported that RaDIANT intervention activities were helpful or very helpful, with
      90.8% of facilities willing to continue at least one intervention component
      beyond the study period. Intervention components with high participation
      emphasized staff and patient-level education, including in-service staff
      orientations, patient and family education programs, and patient educational
      materials. Suggested improvements for intervention activities emphasized
      addressing financial barriers to transplantation, with financial education
      materials perceived as most helpful among RaDIANT educational materials.
      Variation in facility-level fidelity of the RADIANT intervention did not
      significantly influence the mean difference in proportion of patients referred
      pre- (2013) and post-intervention (2014). CONCLUSIONS: We found high fidelity to
      the RaDIANT multicomponent intervention at the majority of intervention
      facilities, with sustainability of select intervention components at intervention
      facilities and feasibility for dissemination across ESRD Networks. Future
      modification of the intervention should emphasize financial education regarding
      kidney transplantation and amend intervention components that facilities perceive
      as time-intensive or non-sustainable. TRIAL REGISTRATION: Clinicaltrials.gov
      number NCT02092727 . Registered 13 Mar 2014 (retrospectively registered).

PMID- 29334902
TI  - Expression characterization of the herbicide tolerance gene Aryloxyalkanoate
      Dioxygenase (aad-1) controlled by seven combinations of regulatory elements.
AB  - BACKGROUND: Availability of well characterized maize regulatory elements for gene
      expression in a variety of tissues and developmental stages provides effective
      alternatives for single and multigene transgenic concepts. We studied the
      expression of the herbicide tolerance gene aryloxyalkanoate dioxygenase (aad-1)
      driven by seven different regulatory element construct designs including the
      ubiquitin promoters of maize and rice, the actin promoters of melon and rice,
      three different versions of the Sugarcane Bacilliform Badnavirus promoters in
      association with other regulatory elements of gene expression. RESULTS: Gene
      expression of aad-1 was characterized at the transcript and protein levels in a
      collection of maize tissues and developmental stages. Protein activity against
      its target herbicide was characterized by herbicide dosage response. Although
      differences in transcript and protein accumulation were observed among the
      different constructs tested, all events were tolerant to commercially relevant
      rates of quizalafop-P-ethyl compared to non-traited maize under greenhouse
      conditions. DISCUSSION: The data reported demonstrate how different regulatory
      elements affect transcript and protein accumulation and how these molecular
      characteristics translate into the level of herbicide tolerance. The level of
      transcript detected did not reflect the amount of protein quantified in a
      particular tissue since protein accumulation may be influenced not only by levels
      of transcript produced but also by translation rate, post-translational
      regulation mechanisms and protein stability. The amount of AAD-1 enzyme produced
      with all constructs tested showed sufficient enzymatic activity to detoxify the
      herbicide and prevent most herbicidal damage at field-relevant levels without
      having a negative effect on plant health. CONCLUSIONS: Distinctive profiles of
      aad-1 transcript and protein accumulation were observed when different regulatory
      elements were utilized in the constructs under study. The ZmUbi and the SCBV
      constructs showed the most consistent robust tolerance, while the melon actin
      construct provided the lowest level of tolerance compared to the other regulatory
      elements used in this study. These data provide insights into the effects of
      differing levels of gene expression and how these molecular characteristics
      translate into the level of herbicide tolerance. Furthermore, these data provide
      valuable information to optimize future designs of single and multiple gene
      constructs for maize research and crop improvement.

PMID- 29334901
TI  - Monitoring vaccine and non-vaccine HPV type prevalence in the post-vaccination
      era in women living in the Basilicata region, Italy.
AB  - BACKGROUND: A large free-of-charge quadrivalent HPV (qHPV) vaccination program,
      covering four cohorts annually (women 11, 14, 17 and 24 years), has been
      implemented in Basilicata since 2007. This study evaluated vaccine and non
      vaccine HPV prevalence 5-7 years post-vaccination program implementation in
      vaccinated and unvaccinated women. METHODS: This population-based, cross
      sectional study was conducted in the public screening centers of the Local Health
      Unit in Matera between 2012 and 2014. Cervical samples were obtained for Pap and
      HPV testing (HC2, LiPA Extra(r) assay) and participants completed a
      sociodemographic and behavioral questionnaire. Detailed HPV vaccination status
      was retrieved from the official HPV vaccine registry. HPV prevalence was
      described overall, by type and vaccination status. The association between HPV
      type-detection and risk/protective factors was studied. Direct vaccine protection
      (qHPV vaccine effectiveness [VE]), cross-protection, and type-replacement were
      evaluated in cohorts eligible for vaccination, by analyzing HPV prevalence of
      vaccine and non-vaccine types according to vaccination status. RESULTS: Overall,
      2793 women (18-50 years) were included, 1314 of them having been in birth cohorts
      eligible for the HPV vaccination program (18- to 30-year-old women at enrolment).
      Among the latter, qHPV vaccine uptake was 59% (at least one dose), with 94%
      completing the schedule; standardized qHPV type prevalence was 0.6% in vaccinated
      versus 5.5% in unvaccinated women (P <0.001); adjusted VE against vaccine type
      infections was 90% (95% CI: 73%-96%) for all fully vaccinated women and 100% (95%
      CI not calculable) in women vaccinated before sexual debut. No statistically
      significant difference in overall high-risk HPV, high-risk non-vaccine HPV, or
      any single non-vaccine type prevalence was observed between vaccinated and
      unvaccinated women. CONCLUSIONS: These results, conducted in a post-vaccine era,
      suggest a high qHPV VE and that a well-implemented catch-up vaccination program
      may be efficient in reducing vaccine-type infections in a real-world setting. No
      cross-protective effect or evidence of type-replacement was observed a few years
      after HPV vaccine introduction.

PMID- 29334903
TI  - A rare case of pericarditis and pleural empyema secondary to transdiaphragmatic
      extension of pyogenic liver abscess.
AB  - BACKGROUND: Transdiaphragmatic extension of pyogenic liver abscess is the rarest
      cause of pericarditis and pleural empyema. It is a rapidly progressive and highly
      lethal infection with mortality rates reaching 100% if left untreated. However,
      the transmission route, treatment methods and prognosis have not been well
      studied. CASE PRESENTATION: A 65-year-old male patient presented with a fever,
      dyspnea, and right upper quadrant abdominal pain. Computed tomography of the
      chest and abdomen showed huge liver abscess without full liquefaction in the left
      lobe, large amount of left pleural effusion, and mild pericardial effusion, and
      the patient was treated with parenteral antibiotics and pigtail insertion at the
      left pleura. However, four days later, cardiac tamponade was developed and
      surgical drainage of the abscess and pericardium was performed. Klebsiella
      pneumonia was isolated from pleural empyema. Twenty-five days after surgery, the
      patient was discharged without any complications. CONCLUSIONS: Herein, we report
      a rare case of pleural empyema and pericarditis in that resulted from the
      extension of huge pyogenic liver abscess. Early surgical treatment may have
      prevented progression of the pericarditis to the more dismal purulent
      pericarditis. We also review pertinent English literature on pericarditis as a
      complication of PLA.

PMID- 29334904
TI  - Association of Kidney Disease Quality of Life (KDQOL-36) with mortality and
      hospitalization in older adults receiving hemodialysis.
AB  - BACKGROUND: For older adults receiving dialysis, health-related quality of life
      is not often considered in prognostication of death or future hospitalizations.
      To determine if routine health-related quality of life measures may be useful for
      prognostication, the objective of this study is to determine the extent of
      association of Kidney Disease Quality of Life (KDQOL-36) subscales with adverse
      outcomes in older adults receiving dialysis. METHODS: This is a longitudinal
      study of 3500 adults aged >=75 years receiving dialysis in the United States in
      2012 and 2013. We used Cox and Fine and Gray models to evaluate the association
      of KDQOL-36 subscales with risk of death and hospitalization. We adjusted for
      sociodemographic variables, hemodialysis access type, laboratory values, and
      Charlson index. RESULTS: Three thousand one hundred thirty-two hemodialysis
      patients completed the KDQOL-36. From KDQOL-36 completion date in 2012, 880
      (28.1%) died and 2023 (64.6%) had at least one hospitalization over a median
      follow-up of 512 and 203 days, respectively. Cohort members with a SF-12 physical
      component summary (PCS) in the lowest quintile had an increased adjusted risk of
      death [hazard ratio (HR), 1.55, 95% confidence interval (CI) 1.19-2.03] and
      hospitalization (HR, 1.29, 95% CI 1.09-1.54) compared with those with scores in
      the highest quintile. Cohort members with a SF-12 mental component summary in the
      lowest quintile had an increased risk of hospitalization (HR, 1.39, 95% CI 1.17
      1.65) compared with those in the highest quintile. In adjusted analyses, there
      was no association between the symptoms of kidney disease, effects of kidney
      disease, and burden of kidney disease subscales with time to death or first
      hospitalization. Competing risk models showed similar HRs. CONCLUSIONS: Among the
      KDQOL-36 subscales, the SF-12 PCS demonstrates the strongest association with
      both death and future hospitalizations in older adults receiving hemodialysis
      Further research is needed to assess the value this subscale may add to
      prognostication.

PMID- 29334905
TI  - Efficacy comparison of multi-phase CT and hepatotropic contrast-enhanced MRI in
      the differential diagnosis of focal nodular hyperplasia: a prospective cohort
      study.
AB  - BACKGROUND: Different clinical behaviour influences the importance of
      differentiating focal nodular hyperplasia (FNH) from other focal liver lesions
      (FLLs). The aim of this study was to compare the efficacy of contrast-enhanced CT
      and MRI in the diagnosis of FNH. METHODS: 157 patients with equivocal FLLs
      detected in ultrasonography subsequently underwent multi-phase CT and MRI with
      the use of hepatotropic contrast agent (Gd-BOPTA) in a 1.5 T scanner.
      Examinations were evaluated by three independent readers. Diagnostic efficacy of
      different radiological signs of FNH in both CT and MRI was compared and AFROC
      analysis was performed. RESULTS: 4 hepatocellular adenomas, 95 hepatocellular
      carcinomas, 98 hemangiomas, 138 metastases and 45 FNHs were diagnosed. In both CT
      and MRI the radiological sign of the highest accuracy was the presence of the
      central scar within FNH (0.93 and 0.96 relatively). The sum of two radiological
      signs in MRI: homogeneous enhancement in hepatic arterial phase (HAP) and
      enhancing lesion in hepatobiliary phase (HBP) was characterized with high values
      of sensitivity (0.89), specificity (0.97), PPV (0.82), NPV (0.98) and accuracy
      (0.96). After inclusion of clinical data into analysis the best discriminating
      feature in MRI was the presence of enhancing lesion in HBP in patients without
      cirrhosis. In this regard, efficacy parameters increased to 1.00, 0.99, 0.94,
      1.00 and 0.99 accordingly. The area under the curve in AFROC analysis of MRI
      performance was significantly larger than of CT (p = 0.0145). CONCLUSION: Gd
      BOPTA-enhanced MRI is a more effective method in the differential diagnosis of
      FNH than multi-phase CT.

PMID- 29334906
TI  - Rationale and design of the CAROLINA(r) - cognition substudy: a randomised
      controlled trial on cognitive outcomes of linagliptin versus glimepiride in
      patients with type 2 diabetes mellitus.
AB  - BACKGROUND: Type 2 diabetes mellitus is associated with cognitive dysfunction and
      an increased risk of dementia. Linagliptin is a glucose-lowering agent of the
      dipeptidyl peptidase-IV (DPP-IV) inhibitor class that is of particular interest
      for the prevention of accelerated cognitive decline, because it may potentially
      benefit the brain through pleiotropic effects, beyond glucose lowering. This
      paper presents the design of a study that aims to establish if linagliptin is
      superior to the sulfonylurea glimepiride in the prevention of accelerated
      cognitive decline in patients with type 2 diabetes mellitus. METHODS: The
      cognition substudy is an integral part of the ongoing event-driven, randomised,
      double blind CARdiOvascular safety of LINAgliptin (CAROLINA(r)) trial, which
      evaluates the effect of treatment with linagliptin versus glimepiride on
      cardiovascular outcomes. CAROLINA(r) includes patients with type 2 diabetes
      mellitus with sub-optimal glycaemic control at elevated cardiovascular risk. The
      substudy will evaluate patients randomised and treated who have a baseline Mini
      Mental State Examination (MMSE) score >= 24, documented years of formal education
      with at least one valid cognitive assessment at baseline and during follow-up.
      The primary cognitive outcome is the occurrence of accelerated cognitive decline
      at the end of follow-up. The two treatment groups will be compared by using a
      logistic regression. Accelerated cognitive decline is defined as a rate of
      cognitive decline that falls at or below the 16th percentile of decline for the
      whole cohort on either the MMSE or a combined score of the trail making and
      verbal fluency test. Potential confounders are taken into account at an
      individual patient level, using a regression based index. DISCUSSION: Between
      December 2010 and December 2012, 6042 patients were randomised and treated with
      either linagliptin (5 mg) or glimepiride (1-4 mg) once daily in CAROLINA(r).
      Cognitive tests were conducted in nearly 4500 participants at baseline and are
      scheduled for two subsequent assessments, after 160 weeks of follow-up and end of
      follow-up. This substudy of the ongoing CAROLINA(r) trial will establish if
      linagliptin is superior to glimepiride in the prevention of accelerated cognitive
      decline in patients with type 2 diabetes mellitus. Final results are expected in
      2019. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT 01243424 .

PMID- 29334907
TI  - Hemodynamic effects of lateral tilt before and after spinal anesthesia during
      cesarean delivery: an observational study.
AB  - BACKGROUND: Post-spinal hypotension is a common maternal complication during
      cesarean delivery. Aortocaval compression by the gravid uterus has been assumed
      as a precipitating factor for post-spinal hypotension. The role of left lateral
      tilting position in improving maternal cardiac output after subarachnoid block
      (SAB) is unclear. The aim of this work is to investigate the effect of left
      lateral tilting on maternal hemodynamics after SAB. METHODS: A prospective
      observational study was conducted including 105 full term pregnant women
      scheduled for cesarean delivery. Mean arterial pressure, heart rate, cardiac
      output (measured by electrical cardiometry), stroke volume, and systemic vascular
      resistance were recorded in three positions (supine, 150, and 300 left lateral
      positions) before SAB, after SAB, and after delivery of the fetus. RESULTS:
      Before SAB, no significant hemodynamic changes were reported with left lateral
      tilting. A significant decrease was reported in mean arterial pressure, cardiac
      output, stroke volume, and systemic vascular resistance after SAB (in supine
      position). When performing left lateral tilting, there was an increase in cardiac
      output, heart rate, and mean arterial pressure. No difference was reported
      between the two tilt angles (150 and 300). CONCLUSIONS: Changing position of full
      term pregnant woman after SAB from supine to left lateral tilted position results
      increased cardiac output and mean arterial pressure. There is no difference
      between the two tilt angles (150 and 300). TRIAL REGISTRATION: clinicaltrials.gov
      ( NCT02828176 ) retrospectively registered.

PMID- 29334908
TI  - Self-reported genital warts among sexually-active university students: a cross
      sectional study.
AB  - BACKGROUND: Genital warts are one of the most common forms of sexually
      transmitted disease, but their epidemiology has yet to be thoroughly elucidated.
      The present study was designed to shed light on the prevalence of clinically
      confirmed, self-reported genital warts (GWs) in a representative sample of the
      university population. METHODS: In 2015, a cross-sectional survey was conducted
      on 11,096 individuals approached at the Students Information Bureau where they
      came to enroll for a university degree course. Participants completed an
      anonymous, self-administered questionnaire providing information on their
      sociodemographic characteristics, sexual behavior, and any history of clinically
      diagnosed genital warts. Multivariate logistic regression was then used to
      identify any factors associated with the disease. RESULTS: Our analysis was
      conducted on 9259 questionnaires (83.4%). Participants were a mean 21.8 +/- 4.8
      years of age, and 59.6% were female. Overall, 124 individuals (1.3%, 95%CI: 1.0
      1.6) reported having been diagnosed with genital warts: 48 men (1.3%, 95%CI: 0.9
      1.6), and 76 women (1.4% 95%CI: 1.1-1.7). Overall, 22.5% of the sample were
      vaccinated (1.3% of the males and 36.8% of the females). The group of respondents
      aged 30 years or more had the highest incidence of genital warts (males: 5.6%,
      95%CI: 2.5-8.6; females: 6.9%, 95%CI: 3.4-10.4). The independent risk factors
      associated with a history of disease were (for both genders) a history of other
      sexually-transmitted diseases, and >=2 sex partners in the previous 24 months. A
      protective role emerged for routine condom use. Additional risk factors
      associated with genital warts in males concerned men who have sex with men,
      bisexuality vis-a-vis heterosexuality, and smoking. CONCLUSIONS: The findings
      emerging from our study help to further clarify the epidemiology of genital warts
      in young people, and may be useful to public health decision-makers. This study
      showed that genital warts occur in men as well as women, and suggests that both
      genders should be monitored for this disease to ascertain the effects of the free
      HPV vaccination offered to all girls in the Veneto in their 12th year of life
      since 2008, and to all boys of the same age since 2015.

PMID- 29334909
TI  - Long term unemployment, income, poverty, and social public expenditure, and their
      relationship with self-perceived health in Spain (2007-2011).
AB  - BACKGROUND: There is scant research that simultaneously analyzes the joint
      effects of long-term unemployment, poverty and public expenditure policies on
      poorer self-perceived health during the financial crisis. The aim of the study is
      to analyze the joint relationship between long-term unemployment, social
      deprivation, and regional social public expenditure on one side, and self
      perceived health in Spain (2007-2011) on the other. METHODS: Longitudinal data
      were extracted from the Survey on Living Conditions, 2007-2010 and 2008-2011
      (9105 individuals and 36,420 observations), which were then used to estimate
      several random group effects in the constant multilevel logistic longitudinal
      models (level 1: year; level 2: individual; level 3: region). The dependent
      variable was self-perceived health. Individual independent interest variables
      were long and very long term unemployment, available income, severe material
      deprivation and regional variables were per capita expenditure on essential
      public services and per capita health care expenditure. RESULTS: All of the
      estimated models show a robust association between bad perceived health and the
      variables of interest. When compared to employed individuals, long term
      unemployment increases the odds of reporting bad health by 22% to 67%; very long
      term unemployment (24 to 48 months) increases the odds by 54% to 132%. Family
      income reduces the odds of reporting bad health by 16% to 28% for each additional
      percentage point in income. Being a member of a household with severe material
      deprivation increases the odds of perceiving one's health as bad by between 70%
      and 140%. Regionally, per capita expenditure on essential public services
      increases the odds of reporting good health, although the effect of this
      association was limited. CONCLUSIONS: Long and very long term unemployment,
      available income and poverty were associated to self-perceived bad health in
      Spain during the financial crisis. Regional expenditure on fundamental public
      services is also associated to poor self-perceived health, although in a more
      limited fashion. Results suggest the positive role in health of active employment
      and redistributing income policies.

PMID- 29334910
TI  - Treatment selection of early stage non-small cell lung cancer: the role of the
      patient in clinical decision making.
AB  - BACKGROUND: The objective of this study is to investigate the role and experience
      of early stage non-small cell lung cancer (NSCLC) patient in decision making
      process concerning treatment selection in the current clinical practice. METHODS:
      Stage I-II NSCLC patients (surgery 55 patients, SBRT 29 patients, median age 68)
      were included in this prospective study and completed a questionnaire that
      explored: (1) perceived patient knowledge of the advantages and disadvantages of
      the treatment options, (2) experience with current clinical decision making, and
      (3) the information that the patient reported to have received from their
      treating physician. This was assessed by multiple-choice, 1-5 Likert Scale, and
      open questions. The Decisional Conflict Scale was used to assess the decisional
      conflict. Health related quality of life (HRQoL) was measured with SF-36
      questionnaire. RESULTS: In 19% of patients, there was self-reported perceived
      lack of knowledge about the advantages and disadvantages of the treatment
      options. Seventy-four percent of patients felt that they were sufficiently
      involved in decision-making by their physician, and 81% found it important to be
      involved in decision making. Forty percent experienced decisional conflict, and
      one-in-five patients to such an extent that it made them feel unsure about the
      decision. Subscores with regard to feeling uninformed and on uncertainty,
      contributed the most to decisional conflict, as 36% felt uninformed and 17% of
      patients were not satisfied with their decision. HRQoL was not influenced by
      patient experience with decision-making or patient preferences for shared
      decision making. CONCLUSIONS: Dutch early-stage NSCLC patients find it important
      to be involved in treatment decision making. Yet a substantial proportion
      experiences decisional conflict and feels uninformed. Better patient information
      and/or involvement in treatment-decision-making is needed in order to improve
      patient knowledge and hopefully reduce decisional conflict.

PMID- 29334912
TI  - Estimating the total prevalence and incidence of end-stage kidney disease among
      Aboriginal and non-Aboriginal populations in the Northern Territory of Australia,
      using multiple data sources.
AB  - BACKGROUND: Most estimates for End Stage Kidney Disease (ESKD) prevalence and
      incidence are based on renal replacement therapy (RRT) registers. However, not
      all people with ESKD will commence RRT and estimates based only on RRT registry
      data will underestimate the true burden of ESKD in the community. This study
      estimates the total number of Northern Territory (NT) residents with ESKD
      including: those receiving RRT, those diagnosed but not receiving RRT and an
      estimate of "undiagnosed" cases. METHODS: Four data sources were used to identify
      NT residents with a diagnosis of ESKD: public hospital admissions, Australia and
      New Zealand Dialysis and Transplant Registry registrations, death registrations
      and, for the Aboriginal population only, electronic primary care records. Three
      data sources contained information recorded between 1 July 2008 and 31 December
      2013, death registration data extended to 31 December 2014 to capture 2013
      prevalent cases. A capture-recapture method was used to estimate both diagnosed
      and undiagnosed cases by making use of probability patterns of overlapping
      multiple data sources. RESULTS: In 2013, the estimated ESKD prevalence in the NT
      Aboriginal population was 11.01 (95% confidence interval (CI) 10.24-11.78) per
      1000, and 0.90 (95% CI 0.76-1.05) per 1000 in the NT non-Aboriginal population.
      The age-adjusted rates were 17.97 (95% CI 17.82-18.11) and 1.07 (95% CI 1.05
      1.09) per 1000 in the NT Aboriginal and non-Aboriginal populations respectively.
      The proportion of individuals receiving RRT was 71.4% of Aboriginal and 75.5% of
      non-Aboriginal prevalent ESKD cases. The age-adjusted ESKD incidence was also
      greater for the Aboriginal (5.26 (95% CI 4.44-6.08) per 1000 population) than non
      Aboriginal population (0.36 (95% CI 0.25-0.47) per 1000). CONCLUSION: This study
      provides comprehensive estimates of the burden of ESKD including those cases that
      are not identified in relevant health data sources. The results are important for
      informing strategies to reduce the total burden of ESKD and to manage the
      potential unmet demand, particularly from comparatively young Aboriginal patients
      who may be suitable for RRT but do not currently access the services for social,
      geographic or cultural reasons.

PMID- 29334911
TI  - Hypocholesterolemia is an independent risk factor for depression disorder and
      suicide attempt in Northern Mexican population.
AB  - BACKGROUND: Cholesterol has been associated as a risk factor for cardiovascular
      disease. Recently, however, there is growing evidence about crucial requirement
      of neuron membrane cholesterol in the organization and function of the 5-HT1A
      serotonin receptor. For this, low cholesterol level has been reported to be
      associated with depression and suicidality. However there have been inconsistent
      reports about this finding and the exact relationship between these factors
      remains controversial. Therefore, we investigated the link between serum
      cholesterol and its fractions with depression disorder and suicide attempt in 467
      adult subjects in Mexican mestizo population. METHODS: Plasma levels of total
      cholesterol, triglycerides, and high-density lipoprotein cholesterol (HDL-c) and
      low density lipoprotein cholesterol (LDL-c) were determined in 261 MDD patients
      meeting the DSM-5 criteria for major depressive disorder (MDD), 59 of whom had
      undergone an episode of suicide attempt, and 206 healthy controls. RESULTS: A
      significant decrease in total cholesterol, LDL-cholesterol, VLDL-cholesterol and
      triglyceride serum levels was observed in the groups of MDD patients and suicide
      attempt compared to those without suicidal behavior (p < 0.05). After adjusting
      for covariates, lower cholesterol levels were significantly associated with MDD
      (OR 4.229 CI 95% 2.555 - 7.000, p<.001) and suicide attempt (OR 5.540 CI 95%
      2.825 - 10.866, p<.001) CONCLUSIONS: These results support the hypothesis that
      lower levels of cholesterol are associated with mood disorders like MDD and
      suicidal behavior. More mechanistic studies are needed to further explain this
      association.

PMID- 29334913
TI  - Identifying enablers and barriers to individually tailored prescribing: a survey
      of healthcare professionals in the UK.
AB  - BACKGROUND: Many people now take multiple medications on a long-term basis to
      manage health conditions. Optimising the benefit of such polypharmacy requires
      tailoring of medicines use to the needs and circumstances of individuals.
      However, professionals report barriers to achieving this in practice. In this
      study, we examined health professionals' perceptions of enablers and barriers to
      delivering individually tailored prescribing. METHODS: Normalisation Process
      Theory (NPT) informed an on-line survey of health professionals' views of
      enablers and barriers to implementation of Individually Tailored Prescribing
      (ITP) of medicines. Links to the survey were sent out through known professional
      networks using a convenience/snowball sampling approach. Survey questions sought
      to identify perceptions of supports/barriers for ITP within the four domains of
      work described by NPT: sense making, engagement, action and monitoring. Analysis
      followed the framework approach developed in our previous work. RESULTS: Four
      hundred and nineteen responses were included in the final analysis (67.3% female,
      32.7% male; 52.7% nurse prescribers, 19.8% pharmacists and 21.8% GPs). Almost
      half (44.9%) were experienced practitioners (16+ years in practice); around one
      third reported already routinely offering ITP to their patients. GPs were the
      group least likely to recognise this as consistent usual practice. Findings
      revealed general support for the principles of ITP but significant variation and
      inconsistency in understanding and implementation in practice. Our findings
      reveal four key implications for practice: the need to raise understanding of ITP
      as a legitimate part of professional practice; to prioritise the work of ITP
      within the range of individual professional activity; to improve the consistency
      of training and support for interpretive practice; and to review the impact of
      formal and informal monitoring processes on practice. CONCLUSION: The findings
      will inform the ongoing development of our new complex intervention (PRIME
      Prescribing) to support the individual tailoring of medicines needed to address
      problematic polypharmacy.

PMID- 29334914
TI  - "Crying without tears" as an early diagnostic sign-post of triple A (Allgrove)
      syndrome: two case reports.
AB  - BACKGROUND: Triple A syndrome (or Allgrove syndrome) is a rare autosomal
      recessive disorder characterized by alacrima, achalasia, adrenal insufficiency
      and autonomic/neurological abnormalities. The majority of cases are caused by
      mutations in the AAAS gene located on chromosome 12q13. However, the clinical
      picture as well as genetic testing may be complex since symptomatology is
      variable and mutations cannot be identified in all clinically diagnosed patients.
      We present two unrelated patients with triple-A syndrome illustrating the
      importance of alacrima as an early clinical sign. CASE PRESENTATION: A 3.5 year
      old girl presented with repeated hypoglycaemic myoclonic events. Adrenal
      insufficiency was diagnosed. In addition, alacrima, obvious since early infancy,
      was incidentally reported by the mother and finally lead to the clinical
      diagnosis of triple A syndrome. This was confirmed by positive mutation analysis
      of the AAAS gene. The second patient, an 8 months old boy was presented because
      of anisocoria and unilateral optic atrophy. MRI revealed cerebellar vermis
      hypotrophy. Psychomotor retardation, failure to thrive, and frequent vomiting
      lead to further diagnostic work-up. Achalasia was diagnosed radiologically. In
      addition, the mother mentioned absence of tears since birth leading to the
      clinical diagnosis of triple A syndrome. In contrast to the first cases genetic
      testing was negative. CONCLUSION: These two patients illustrate the heterogeneity
      of triple A syndrome in both terms, clinical expression and genetic testing. We
      particularly aim to stress the importance of alacrima, which should be considered
      as a red flag symptom. Further differential diagnosis is required in every child
      affected by alacrima.

PMID- 29334916
TI  - Influence of drought stress on afalfa yields and nutritional composition.
AB  - BACKGROUND: It is predicted that climate change may increase the risk of local
      droughts, with severe consequences for agricultural practices. METHODS: Here we
      report the influence of drought on alfalfa yields and nutritional composition,
      based on artificially induced drought conditions during two field experiments.
      Two types of alfalfa cultivars were compared, Gold Queen and Suntory. The
      severity and timing of drought periods were varied, and the crop was harvested
      either early during flowering, or late at full bloom. RESULTS: The obtained dry
      mass yields of Gold Queen were higher than Suntory, and the first was also more
      resistant to drought. Early harvest resulted in higher yields. Decreases in
      yields due to water shortage were observed with both cultivars, and the fraction
      of crude protein (CP) decreased as a result of drought stress; this fraction was
      higher in Gold Queen than in Suntory and higher in early harvest compared to late
      harvest. Severe drought late in spring had the highest effect on CP content. The
      fraction of fibre, split up into neutral detergent fibre (NDF) and acid detergent
      fibre (ADF) increased as a result of drought and was lower in early compared to
      late harvested plants. Suntory alfalfa produced higher fibre fractions than Gold
      Queen. The fraction of water-soluble carbohydrates (WSC) was least affected by
      drought. It was consistently higher in Gold Queen compared to Suntory alfalfa,
      and late harvest resulted in higher WSC content. CONCLUSIONS: In combination,
      these results suggest that the nutritive value of alfalfa will likely decrease
      after a period of drought. These effects can be partly overcome by choosing the
      Gold Queen cultivar over Suntory, by targeted irrigation, in particular in late
      spring, and by harvesting at an earlier time.

PMID- 29334915
TI  - Monitoring the responsiveness of T and antigen presenting cell compartments in
      breast cancer patients is useful to predict clinical tumor response to
      neoadjuvant chemotherapy.
AB  - BACKGROUND: Vaccination of mice with tumors treated with Doxorubicin promotes a T
      cell immunity that relies on dendritic cell (DC) activation and is responsible
      for tumor control in vaccinated animals. Despite Doxorubicin in combination with
      Cyclophosphamide (A/C) is widely used to treat breast cancer patients, the
      stimulating effect of A/C on T and APC compartments and its correlation with
      patient's clinical response remains to be proved. METHODS: In this prospective
      study, we designed an in vitro system to monitor various immunological readouts
      in PBMCs obtained from a total of 17 breast cancer patients before, and after
      neoadjuvant anti-tumor therapy with A/C. RESULTS: The results show that before
      treatment, T cells and DCs, exhibit a marked unresponsiveness to in vitro
      stimulus: whereas T cells exhibit poor TCR internalization and limited expression
      of CD154 in response to anti-CD3/CD28/CD2 stimulation, DCs secrete low levels of
      IL-12p70 and limited CD83 expression in response to pro-inflammatory cytokines.
      Notably, after treatment the responsiveness of T and APC compartments was
      recovered, and furthermore, this recovery correlated with patients' residual
      cancer burden stage. CONCLUSIONS: Our results let us to argue that the model used
      here to monitor the T and APC compartments is suitable to survey the recovery of
      immune surveillance and to predict tumor response during A/C chemotherapy.

PMID- 29334917
TI  - Obesity and breast cancer outcomes in chemotherapy patients in New Zealand - a
      population-based cohort study.
AB  - BACKGROUND: Obesity has been reported as an adverse prognostic factor in breast
      cancer, but inconsistently, and under-treatment with chemotherapy may occur. We
      provide the first assessment of obesity and breast cancer outcomes in a
      population-based, multi-ethnic cohort of New Zealand patients treated with
      chemotherapy. METHODS: All 3536 women diagnosed with invasive breast cancer in
      the Waikato region of New Zealand from 2000-2014 were registered and followed
      until last follow-up in specialist or primary care, death or Dec 2014; median
      follow-up 4.1 years. For the 1049 patients receiving chemotherapy, mortality from
      breast cancer, other causes, and all causes, and rates of loco-regional and of
      distant recurrence, were assessed by body mass index (BMI), recorded after
      diagnosis, adjusting for other clinico-pathological and demographic factors by
      Cox regression. RESULTS: BMI was known for 98% (n=1049); 33% were overweight (BMI
      25-29.9), 21% were obese (BMI 30-34.9), and 14% were very obese (BMI 35+). There
      were no significant associations between obesity and survival, after adjustment
      for demographic and clinical factors (hazard ratios, HR, for very obese compared
      to BMI 21-24, for breast cancer deaths 0.96 (0.56-1.67), and for all deaths 1.03
      (0.63-1.67), respectively, and only small non-significant associations for loco
      regional or metastatic recurrence rates (HR 1.17 and 1.33 respectively). Subgroup
      analyses by age, menopausal status, ethnicity, stage, post-surgical radiotherapy,
      mode of diagnosis, type of surgery, and receptor status, showed no associations.
      No associations were seen with BMI as a continuous variable. The results in all
      patients irrespective of treatment but with recorded BMI data (n=2296) showed
      similar results. CONCLUSIONS: In this population, obesity assessed post-diagnosis
      had no effect on survival or recurrence, based on 1049 patients with chemotherapy
      treatment with follow-up up to 14 years.

PMID- 29334919
TI  - Low birthweight in rural Cameroon: an analysis of a cut-off value.
AB  - BACKGROUND: Low birthweight (LBW) is a major predictor of early neonatal
      mortality which disproportionately affects low-income countries. WHO recommends
      regional definitions for LBW to prevent misclassifications and ensure appropriate
      care of babies with LBW. We conducted this study to define a clinical cut-off for
      LBW, and to determine the predictors and adverse foetal outcomes of LBW babies in
      a rural sub-division in Cameroon. METHODS: We conducted a retrospective register
      analysis of 1787 singleton deliveries in two health facilities in the Northwest
      Region of Cameroon. Records with no birthweight or birthweight less than 1000 g,
      babies born before arrival, multiple deliveries and deliveries before 28 weeks
      gestation were excluded from this study. The 10th percentile of birthweights was
      computed to obtain a statistical cut-off value for the LBW. To assess the
      clinical significance of the newly defined cut-off value, we compared the
      prevalence of adverse foetal outcomes between LBW (birthweight <10th percentile)
      and heavier babies (birthweight >=10th percentile) in our study population.
      RESULTS: The 10th percentile of the birthweights was 2700 g. Preterm delivery was
      the lone predictor of LBW (aOR = 2.0, 95% CI = 1.3-3.1; p = 0.001). LBW babies
      were more likely to be stillborn (OR = 9.6; 95% CI = 4.2-21.6; p < 0.001) or
      asphyxiated at the 5th minute (OR = 2.0; 95% CI = 1.2-3.3; p = 0.006), compared
      with heavier babies. Also, 6.1% of babies who had a birthweight between 2500 and
      2700 g were more likely to be stillborn compared to heavier babies. CONCLUSION:
      This study suggests that the clinical cut-off for LBW in this rural community is
      2700 g; with 6.1% of babies born with LBW probably receiving inadequate care as
      the traditional cut-off value of 2500 g proposed by WHO is still used to define
      LBW in our setting. Further studies are necessary to define a national cut-off
      value for harmonisation of LBW definitions in the country to prevent
      misclassifications and ensure appropriate neonatal care.

PMID- 29334918
TI  - Colorectal cancer liver metastases - a population-based study on incidence,
      management and survival.
AB  - BACKGROUND: Colorectal cancer (CRC) is a leading cause of cancer-associated
      deaths with liver metastases developing in 25-30% of those affected. Previous
      data suggest a survival difference between right- and left-sided liver metastatic
      CRC, even though left-sided cancer has a higher incidence of liver metastases.
      The aim of the study was to describe the liver metastatic patterns and survival
      as a function of the characteristics of the primary tumour and different
      combinations of metastatic disease. METHODS: A retrospective population-based
      study was performed on a cohort of patients diagnosed with CRC in the region of
      Stockholm, Sweden during 2008. Patients were identified through the Swedish
      National Quality Registry for Colorectal Cancer Treatment (SCRCR) and additional
      information on intra- and extra-hepatic metastatic pattern and treatment were
      retrieved from electronic patient records. Patients were followed for 5 years or
      until death. Factors influencing overall survival (OS) were investigated by means
      of Cox regression. OS was compared using Kaplan-Meier estimations and the log
      rank test. RESULTS: Liver metastases were diagnosed in 272/1026 (26.5%) patients
      within five years of diagnosis of the primary. Liver and lung metastases were
      more often diagnosed in left-sided colon cancer compared to right-sided cancer
      (28.4% versus 22.1%, p = 0.029 and 19.7% versus 13.2%, p = 0.010, respectively)
      but the extent of liver metastases were more extensive for right-sided cancer as
      compared to left-sided (p = 0.001). Liver metastatic left-sided cancer, including
      rectal cancer, was associated with a 44% decreased mortality risk compared to
      right-sided cancer (HR = 0.56, 95% CI: 0.39-0.79) with a 5-year OS of 16.6%
      versus 4.3% (p < 0.001). In liver metastatic CRC, the presence of lung metastases
      did not significantly influence OS as assessed by multivariate analysis (HR =
      1.11, 95% CI: 0.80-1.53). CONCLUSION: The worse survival in liver metastatic
      right-sided colon cancer could possibly be explained by the higher number of
      metastases, as well as more extensive segmental involvement compared with left
      sided colon and rectal cancer, even though the latter had a higher incidence of
      liver metastases. Detailed population-based data on the metastatic pattern of CRC
      and survival could assist in more structured and individualized guidelines for
      follow-up of patients with CRC.

PMID- 29334920
TI  - Factors influencing access of pregnant women and their infants to their local
      healthcare system: a prospective, multi-centre, observational study.
AB  - BACKGROUND: The successful implementation of maternal vaccination relies on
      results of clinical trials, considering the prenatal and postnatal attendance at
      selected healthcare institutions. This study evaluated factors influencing
      maternal/infant access to healthcare facilities to identify potential barriers to
      participation in future clinical trials on maternal vaccination. METHODS: In this
      prospective, multi-centre, observational study, pregnant women (N = 3243) were
      enrolled at ten sites across Panama, the Dominican Republic, South Africa, and
      Mozambique between 2012 and 2014. They completed questionnaires at enrolment,
      delivery, and infant follow-up (90 days post-partum) visits, including questions
      on transportation, phone accessibility, alternative childcare, gestational age at
      enrolment, delivery location, and health status of their infant. Logistic
      regression was used to identify factors significantly associated with return to
      study site for delivery or infant follow-up visits. RESULTS: Among 3229 enrolled
      women with delivery information, 63.6% (range across sites: 25.3-91.5%) returned
      to study site for delivery. Older women and those at later gestational age at
      enrolment were more likely to deliver at the study site. While heterogeneities
      were observed at site level, shorter travel time at delivery and increased
      transportation costs at enrolment were associated with increased likelihood of
      women returning to study site for delivery. Among 3145 women with live-born
      infants, 3077 (95.3%) provided 90-day follow-up information; of these, 68.9%
      (range across sites: 25.6-98.9%) returned to study site for follow-up visits.
      Women with other children and with lower transportation costs at delivery were
      more likely to return to study site for follow-up visits. Among 666 infants
      reported sick, 94.3% were taken to a healthcare facility, with only 41.9% (range
      across sites: 4.9-77.3%) to the study site. CONCLUSION: Although high retention
      was observed from enrolment through 90 days after delivery, post-partum
      surveillance should be broadened beyond the study sites and additional follow-up
      visits should be planned within the neonatal period. The factors influencing
      maternal/infant access to healthcare facilities and the issues identified in this
      study should be taken into consideration in planning future clinical studies on
      maternal immunisation in low- and middle-income countries. TRIAL REGISTRATION:
      The study was registered at ClinicalTrial.gov ( NCT01734434 ) on November 22,
      2012.

PMID- 29334921
TI  - A pilot feasibility randomised controlled trial of an adjunct brief social
      network intervention in opiate substitution treatment services.
AB  - BACKGROUND: Approximately 3% of people receiving opioid substitution therapy
      (OST) in the UK manage to achieve abstinence from prescribed and illicit drugs
      within three years of commencing treatment. Involvement of families and wider
      social networks in supporting psychological treatment may be an effective
      strategy in facilitating recovery, and this pilot study aimed to evaluate the
      impact of a social network-focused intervention for patients receiving OST.
      METHODS: A two-site, open feasibility trial randomised patients receiving OST for
      at least 12 months but still reporting illicit opiate use in the past 28 days to
      one of three treatments: 1) treatment as usual (TAU), 2) Brief Social Behaviour
      and Network Therapy (B-SBNT) + TAU, or 3) Personal Goal Setting (PGS) + TAU. The
      two active interventions consisted of 4 sessions. There were 3 aims: 1) test the
      feasibility of recruiting OST patients to a trial of B-SBNT, and following them
      up over 12 months; 2) test the feasibility of training clinicians to deliver B
      SBNT; 3) test whether B-SBNT reduces heroin use 3 and 12 months after treatment,
      and to explore potential mediating factors. The primary outcome for aim 3 was
      number of days of heroin use in the past month, and a range of secondary outcome
      measures were specified in advance (level of drug dependence, mental health,
      social satisfaction, therapist rapport, treatment satisfaction, social network
      size and support). RESULTS: A total of 83 participants were randomised, and 70
      (84%) were followed-up at 12 months. Fidelity analysis of showed that B-SBNT
      sessions were clearly distinguishable from PGS and TAU sessions, suggesting it
      was possible to train clinical staff to an adequate level of competence. No
      significant differences were found between the 3 intervention arms in the primary
      or secondary outcome measures. Attendance at psychosocial treatment intervention
      sessions was low across all three arms (44% overall). CONCLUSIONS: Patients
      receiving OST can be recruited into a trial of a social network-based
      intervention, but poor attendance at treatment sessions makes it uncertain
      whether an adequate dose of treatment was delivered. In order to achieve the
      benefits of psychosocial interventions, further work is needed to overcome poor
      engagement. TRIAL REGISTRATION: ISRCTN Trial Registration Number: ISRCTN22608399
      . Date of registration: 27/04/2012. Date of first randomisation: 14/08/2012.

PMID- 29334922
TI  - Relative contribution of various chronic diseases and multi-morbidity to
      potential disability among Dutch elderly.
AB  - BACKGROUND: The amount of time spent living with disease greatly influences
      elderly people's wellbeing, disability and healthcare costs, but differs by
      disease, age and sex. METHODS: We assessed how various single and combined
      diseases differentially affect life years spent living with disease in Dutch
      elderly men and women (65+) over their remaining life course. Multistate life
      table calculations were applied to age and sex-specific disease prevalence,
      incidence and death rates for the Netherlands in 2007. We distinguished
      congestive heart failure, coronary heart disease (CHD), breast and prostate
      cancer, colon cancer, lung cancer, diabetes, COPD, stroke, dementia and
      osteoarthritis. RESULTS: Across ages 65, 70, 75, 80 and 85, CHD caused the most
      time spent living with disease for Dutch men (from 7.6 years at age 65 to 3.7
      years at age 85) and osteoarthritis for Dutch women (from 11.7 years at age 65 to
      4.8 years at age 85). Of the various co-occurrences of disease, the combination
      of diabetes and osteoarthritis led to the most time spent living with disease,
      for both men (from 11.2 years at age 65 to 4.9 -years at age 85) and women (from
      14.2 years at age 65 to 6.0 years at age 85). CONCLUSIONS: Specific single and
      multi-morbid diseases affect men and women differently at different phases in the
      life course in terms of the time spent living with disease, and consequently,
      their potential disability. Timely sex and age-specific interventions targeting
      prevention of the single and combined diseases identified could reduce healthcare
      costs and increase wellbeing in elderly people.

PMID- 29334923
TI  - Relationship between corneal biomechanical properties and structural biomarkers
      in patients with normal-tension glaucoma: a retrospective study.
AB  - BACKGROUND: We evaluated the relationships between corneal biomechanical
      properties and structural parameters in patients with newly diagnosed, untreated
      normal-tension glaucoma (NTG). METHODS: All subjects were evaluated using an
      Ocular Response Analyzer (ORA) measuring corneal hysteresis (CH) and the corneal
      resistance factor (CRF). Central corneal thickness (CCT), Goldmann applanation
      tonometric (GAT) data, axial length, and the spherical equivalent (SE), were also
      measured. Confocal scanning laser ophthalmoscopy was performed with the aid of a
      Heidelberg retina tomograph (HRT III). We sought correlations between HRT
      parameters and different variables including CCT, CH, and the CRF. Multiple
      linear regression analysis was performed to identify significant associations
      between corneal biomechanical properties and optic nerve head parameters.
      RESULTS: We enrolled 95 eyes of 95 NTG patients and 93 eyes of 93 normal
      subjects. CH and the CRF were significantly lower in more advanced glaucomatous
      eyes (P = 0.001, P = 0.008, respectively). The rim area, rim volume, linear cup
      to-disc ratio (LCDR), and mean retinal nerve fiber layer (RNFL) thickness were
      significantly worse in more advanced glaucomatous eyes (P < 0.001, P < 0.001, P <
      0.001, and P = 0.001). CH was directly associated with rim area, rim volume, and
      mean RNFL thickness (P = 0.012, P = 0.028, and P = 0.043) and inversely
      associated with LCDR (P = 0.015), after adjusting for age, axial length, CCT,
      disc area, GAT data, and SE. However, in normal subjects, there were no
      significant associations between corneal biomechanical properties and HRT
      parameters. CONCLUSIONS: A lower CH is significantly associated with a smaller
      rim area and volume, a thinner RNFL, and a larger LCDR, independent of disc size,
      corneal thickness, intraocular pressure, and age.

PMID- 29334924
TI  - Longitudinal observation of subretinal fibrosis in Vogt-Koyanagi-Harada disease.
AB  - BACKGROUND: Subretinal fibrosis (SRF) is a vision-threatening complication of
      Vogt-Koyanagi-Harada disease (VKH). It has long been recognized as a sequela of
      chronic inflammation. The developmental process of SRF, however, has not been
      described. The purpose of this study is to provide longitudinal observations of
      SRF in VKH. METHODS: Retrospective chart review of 10 VKH patients referred to
      our group between January 2008 and September 2015 at acute uveitic stage with SRF
      at presentation or who developed SRF during follow up. RESULTS: Ten patients (6
      males and 4 females) with a median age of 39.0 (range, 23 to 58) years old were
      included. The median disease duration at presentation and median duration of
      follow up were 25.5 (range 5 to 60) days and 32.5 (range 13 to 61) months
      respectively. At presentation, all patients except one had been inappropriately
      treated with glucocorticosteroid (insufficiently dosed or tapered too fast) for
      longer than 2 weeks. Despite large dose oral glucocorticosteroid (1 mg/kg/d
      prednisone or equivalent) with slow tapering in combination with at least one
      immunomodulatory agent (cyclosporin A, cyclophosphamide or azathioprine) after
      presentation, all patients developed bilateral SRF within the first 4 months of
      disease course and 7 patients within the first 2 months. In 8 patients, shape
      change/migration and progressive proliferation/pigmentation of SRF was observed
      over a period of several months after its formation, and then became quiescent
      but may further underwent depigmentation or pigmentation. SRF involved macula in
      12 eyes (7 patients) and caused treatment resistant macular detachment and severe
      visual impairment in 6 eyes (4 patients). At the last visit, eyes with macular
      involvement were more common to had worse final best corrected visual acuity
      (<=20/50) than those without (9/12 vs. 0/8, p = 0.001). CONCLUSIONS: SRF usually
      develop early in the disease course in VKH patients who are not adequately
      controlled; it usually undergoes a highly dynamic process within the subretinal
      space and may involve the macula and resulted in poor final visual outcome.

PMID- 29334925
TI  - Implementing blended learning in emergency airway management training: a
      randomized controlled trial.
AB  - BACKGROUND: While emergency airway management training is conventionally
      conducted via face-to-face learning (F2FL) workshops, there are inherent cost,
      time, place and manpower limitations in running such workshops. Blended learning
      (BL) refers to the systematic integration of online and face-to-face learning
      aimed to facilitate complex thinking skills and flexible participation at a
      reduced financial, time and manpower cost. This study was conducted to evaluate
      its effectiveness in emergency airway management training. METHODS: A single
      center prospective randomised controlled trial involving 30 doctors from Sarawak
      General Hospital, Malaysia was conducted from September 2016 to February 2017 to
      compare the effectiveness of BL versus F2FL for emergency airway management
      training. Participants in the BL arm were given a period of 12 days to go through
      the online materials in a learning management system while those in the F2FL arm
      attended a-day of face-to-face lectures (8 h). Participants from both arms then
      attended a day of hands-on session consisting of simulation skills training with
      airway manikins. Pre- and post-tests in knowledge and practical skills were
      administered. E-learning experience and the perception towards BL among
      participants in the BL arm were also assessed. RESULTS: Significant improvements
      in post-test scores as compared to pre-test scores were noted for participants in
      both BL and F2FL arms for knowledge, practical, and total scores. The degree of
      increment between the BL group and the F2FL arms for all categories were not
      significantly different (total scores: 35 marks, inter-quartile range (IQR) 15.0 
      41.0 vs. 31 marks, IQR 24.0 - 41.0, p = 0.690; theory scores: 18 marks, IQR 9 -
      24 vs. 19 marks, IQR 15 - 20, p = 0.992; practical scores: 11 marks, IQR 5 -18
      vs. 10 marks, IQR 9 - 20, p = 0.461 respectively). The overall perception towards
      BL was positive. CONCLUSIONS: Blended learning is as effective as face-to-face
      learning for emergency airway management training of junior doctors, suggesting
      that blended learning may be a feasible alternative to face-to-face learning for
      such skill training in emergency departments. TRIAL REGISTRATION: Malaysian
      National Medical Research NMRR-16-696-30190 . Registered 28 April 2016.

PMID- 29334926
TI  - (R)-alpha-Lipoic acid inhibits fructose-induced myoglobin fructation and the
      formation of advanced glycation end products (AGEs) in vitro.
AB  - BACKGROUND: Fructose-mediated protein glycation (fructation) has been linked to
      an increase in diabetic and cardiovascular complications due to over consumption
      of high-fructose containing diets in recent times. The objective of the present
      study is to evaluate the protective effect of (R)-alpha-lipoic acid (ALA) against
      fructose-induced myoglobin fructation and the formation of advanced glycation end
      products (AGEs) in vitro. METHODS: The anti-glycation activity of ALA was
      determined using the formation of AGEs fluorescence intensity, iron released from
      the heme moiety of myoglobin and the level of fructosamine. The fructation
      induced myoglobin oxidation was examined using the level of protein carbonyl
      content and thiol group estimation. RESULTS: The results showed that co
      incubation of myoglobin (1 mg/mL), fructose (1 M) and ALA (1, 2 and 4 mM)
      significantly inhibited the formation of AGEs during the 30 day study period. ALA
      markedly decreased the levels of fructosamine, which is directly associated with
      the reduction of AGEs formation. Furthermore, ALA significantly reduced free iron
      release from myoglobin which is attributed to the protection of myoglobin from
      fructose-induced glycation. The results also demonstrated a significant
      protective effect of ALA on myoglobin oxidative damages, as seen from decreased
      protein carbonyl content and increased protein thiols. CONCLUSION: These findings
      provide new insights into the anti-glycation properties of ALA and emphasize that
      ALA supplementation is beneficial in the prevention of AGEs-mediated diabetic and
      cardiovascular complications.

PMID- 29334927
TI  - Dexmedetomidine prevents acute kidney injury after adult cardiac surgery: a meta
      analysis of randomized controlled trials.
AB  - BACKGROUND: Dexmedetomidine has been shown to confer direct renoprotection by
      stabilizing the sympathetic system, exerting anti-inflammatory effects and
      attenuating ischemia/reperfusion (I/R) injury in preclinical studies. Results
      from clinical trials of dexmedetomidine on acute kidney injury (AKI) following
      adult cardiac surgery are controversial. METHODS: We searched EMBASE, PubMed, and
      Cochrane CENTRAL databases for randomized controlled trials (RCTs) comparing the
      renal effect of dexmedetomidine versus placebo or other anesthetic drugs in adult
      patients undergoing cardiac surgery. The primary outcome was the incidence of
      AKI. The secondary outcomes were mechanical ventilation (MV) duration, intensive
      care unit (ICU) stay and hospital length of stay(LOS), and postoperative
      mortality (in-hospital or within 30 days). RESULTS: Ten trials with a total of
      1575 study patients were selected. Compared with controls, dexmedetomidine
      significantly reduced the incidence of postoperative AKI [68/788 vs 97/787; odds
      ratio(OR), 0.65; 95% confidence interval (CI), 0.45-0.92; P = 0.02; I2 = 0.0%],
      and there was no difference between groups in postoperative mortality (4/487 vs
      11/483; OR, 0.43; 95% CI, 0.14-1.28; P = 0.13; I2 = 0.0%), MV duration [in days;
      n = 1229; weighted mean difference(WMD), -0.22; 95% CI, -2.04 to 1.70; P = 0.81],
      ICU stay (in days; n = 1363; WMD, -0.85; 95% CI, -2.14 to 0.45; P = 0.20), and
      hospital LOS (in days; n = 878; WMD, -0.24; 95% CI, -0.71 to 0.23; P = 0.32).
      CONCLUSIONS: Perioperative administration of dexmedetomidine in adult patients
      undergoing cardiac surgery may reduce the incidence of postoperative AKI. Future
      trials are needed to determine the dose and timing of dexmedetomidine in
      improving outcomes, especially in patients with decreased baseline kidney
      function.

PMID- 29334928
TI  - Consumption of sweetened-beverages and poverty in Colombia: when access is not an
      advantage.
AB  - BACKGROUND: This study characterizes the intake of sweetened beverages and
      establishes whether economic inequalities in their consumption exists. METHODS:
      Ecological study. Mixed methods using food frequency questionnaire and inequality
      indices. Based on the National Nutrition Survey, Colombia, 2010. The sweetened
      beverage intake of 17,514 subjects in 33 geodemographic units was estimated with
      a food frequency questionnaire and summarized. The calculation of inequality was
      based on the monetary poverty. The prevalence (yes/no) and frequency (times/day)
      of sweetened beverage consumption were estimated. Indices of economic inequality
      were calculated for both prevalence and frequency. RESULTS: The prevalence of
      sweetened beverage consumption was between 79.2% (95% CI, 75.7 to 82.8) in adults
      and 88.5% (95% CI, 85.8 to 91.3) in minors. The frequency of consumption in terms
      of times/day, was between 0.20 (95% CI, 0.16 to 0.24) in adults and 0.40 (95% CI,
      0.33 to 0.46) in minors. The Gini coefficient for the prevalence was close to
      zero, between 0.04 and 0.08; for the frequency, it was slightly higher, between
      0.12 and 0.25. CONCLUSIONS: It was established that there is no economic
      inequality in the consumption of sweetened beverages. Consumption taxes could be
      regressive.

PMID- 29334929
TI  - Chronic kidney disease in sugarcane workers in Cameroon: a cross-sectional study.
AB  - BACKGROUND: Agricultural workers especially in sugarcane plantations have a high
      risk of chronic kidney disease (CKD). Little is known about CKD among sugarcane
      plantation workers in Cameroon. This study sought to evaluate the prevalence and
      identify factors associated with CKD in sugarcane plantation workers in Cameroon.
      METHODS: We conducted an analytic cross-sectional study including 204 adult
      workers at the sugarcane plantation complex in Mbandjock, Cameroon; over 500 m
      above sea level. Chronic kidney disease (proteinuria as estimated by urine
      dipstick analysis and/or estimated glomerular filtration rate < 60 ml/min/1.73 m2
      persistent after 3 months) was the outcome of interest. Those with abnormal
      results were seen again after 3 months to confirm the diagnosis. We evaluated the
      association between CKD and participant age, sex, contract-type, duration of
      employment, socio-economic status, workspace, exposure to agrochemicals, heavy
      metals and heat, selected risk factors and co-morbid conditions. RESULTS: The
      overall prevalence of CKD was 3.4%. The factory workers were the most affected
      (7%), compared to the field (2.4%) and office workers (0%). 2.9% of the
      participants had persistent proteinuria, mild in every case, and 0.5% of them had
      an estimated glomerular filtration rate < 60 ml/min/1.73 m2. Age >= 40 years was
      an independent predictor of CKD. CONCLUSION: The prevalence of CKD among
      employees of the Mbandjock sugarcane plantation is low, probably reflecting the
      preventive measures against heat stress and dehydration in place.

PMID- 29334930
TI  - Safety and adequacy of percutaneous kidney biopsy performed by nephrology
      trainees.
AB  - BACKGROUND: Recently there has been a progressive loss of specialty related
      skills for nephrologists. Among the skills we find the kidney biopsy that has a
      central role in diagnosis of renal parenchymal disease. One of the causes might
      be the belief that the kidney biopsy should be performed only in larger Centers
      which can rely on the presence of a renal pathologist and on nephrologists with a
      large experience. This trend may increase in the short term procedural safety but
      may limit the chance of in training nephrologists to become confident with the
      technique. METHODS: We evaluated renal biopsies performed from May 2002 to
      October 2016 in our Hospital, a mid-sized facility to determine whether the
      occurrence of complications would be comparable to those reported in literature
      and whether the increase in the number of biopsy performing physicians including
      nephrology fellows which took place since January 2012, after our Nephrology Unit
      became academic, would be associated to an increase of complications or a
      reduction of diagnostic power of renal biopsies. Three hundred thirty seven
      biopsies were evaluated. Patients underwent ultrasound guided percutaneous renal
      biopsy using a 14 G core needle loaded on a biopsy gun. Observation lasted for 24
      h, we evaluated hemoglobin levels 6 and 24 h and kidney ultrasound 24 h after the
      biopsy. RESULTS: Complications occurred in 18.7% of patients, of these only 1,2%
      were major complications. Complications were more common in female (28%) compared
      to male patients (14,8%) (p = 0.004). We found no correlation between diagnosis,
      kidney function and complication rates; hypertension was not associated to a
      higher risk in complications. The increase of biopsy performing personnel was not
      associated to an increase in complication rates (18,7% both pre and post 2012) or
      with an increase of major complications (1.2% vs 1,2%). CONCLUSIONS: Kidney
      biopsy can be safely performed in mid-sized hospitals. Safety and adequacy are
      guaranteed even if the procedure is performed by a larger number of less
      experienced nephrologists as long as under tutor supervision, thus kidney biopsy
      should become an integral part of a nephrology fellow training allowing more
      widespread diffusion of this technique.

PMID- 29334931
TI  - In vitro antibacterial and antibiotic modifying activity of crude extract,
      fractions and 3',4',7-trihydroxyflavone from Myristica fragrans Houtt against MDR
      Gram-negative enteric bacteria.
AB  - BACKGROUND: Nutmeg is the seed kernel inside the fruit of Myristica fragrans
      Houtt. (Myristicaceae). It possesses various pharmacological activities but is
      used in Cameroon only for its flavor in making cakes. The present study thus
      aimed to investigate the in vitro antibacterial activity and antibiotic modifying
      activities of crude seed kernel methanol extract (MFS), fractions (MFSa-e) as
      well as 3',4',7-trihydroxyflavone from Myristica fragrans against a panel of
      multi-drug resistant (MDR) Gram-negative bacteria. METHODS: The modified rapid p
      iodonitrotetrazolium chloride (INT) colorimetric assay was used to determine the
      Minimal Inhibitory Concentration (MIC) and Minimal Bactericidal Concentration
      (MBC) on the tested bacteria, as well as those of antibiotics in association with
      the extract and/or isolated compound. Column chromatography was used for the
      fractionation and purification of the seed kernel extract whilst the chemical
      structures of compounds were determined using spectroscopic techniques. RESULTS:
      Phytochemical investigations lead to the isolation of 3',4',7-trihydroxyflavone
      from the fraction MFSb. The crude extract showed antibacterial activity with MICs
      ranging from 32 to 1024 MUg/mL on the majority of the 29 tested Gram-negative
      bacterial strains. Fraction MFSb inhibited the growth of 100% (29/29) of the
      tested bacterial strains, as well as the compound 3',4',7-trihydroxyflavone
      (12/12) with a MIC values ranging from 32 to 1024 MUg/mL, and 4 to 128 MUg/mL
      respectively. The lowest MIC value (4 MUg/mL) was recorded with 3',4',7
      trihydroxyflavone against Providencia stuartii ATCC299645 as well as the best MBC
      value (16 MUg/mL) against the same strain. In the presence of Phenylalanine
      Arginine-beta-Naphthylamide (PAbetaN), an efflux pumps inhibitor, the activity of
      the extract increased on 73.33% (11/15) meanwhile that of 3',4',7
      trihydroxyflavone increased on 100% tested bacteria. The compound 3',4',7
      trihydroxyflavone potentiated the activity of antibiotics in the majority of the
      tested bacterial strains. CONCLUSION: The results of the present work provide
      additional information on the use of nutmeg and it major antibacterial component,
      3',4',7-trihydroxyflavone, as a potential drug in the treatment of bacterial
      infections including multidrug resistant phenotypes.

PMID- 29334932
TI  - Anemia in people on second line antiretroviral treatment in Lilongwe, Malawi: a
      cross-sectional study.
AB  - BACKGROUND: Anemia is common among people living with HIV infection and is
      frequently associated with poor quality of life and poor prognosis. It has been
      well described in antiretroviral naive individuals and those on non-nucleoside
      reverse transcriptase inhibitor-based first line antiretroviral therapy (ART)
      regimens. However there is limited information on anemia for ART experienced
      individuals on protease inhibitor-based second line ART regimens in resource
      limited settings. Our objective was to describe the prevalence and risk factors
      of anemia in this ART experienced population in Malawi. METHODS: We conducted a
      cross-sectional study using routine facility data at two HIV clinics in Lilongwe,
      Malawi. The analysis included individuals receiving protease inhibitor-based
      second line ART. Clinical and laboratory data were collected at routine clinic
      visits. We used descriptive statistics, two-sample t-tests and multivariate
      logistic regression for data analysis. RESULTS: Three hundred seventy-seven
      records were included in this analysis (37% male, median age 41 years, median CD4
      count 415 cells/MUL). The prevalence of anemia was 125/377 (33.2%) - mild,
      moderate and severe anemia was 17.5%, 13.8%, and 1.9% respectively. Female
      participants had a higher prevalence than male participants (43.6% vs. 15.7%, p <
      0.001). In multivariate logistic regression, female sex (adjusted odds ratio
      (aOR) 5.3; 95% CI 2.9-9.5) and a CD4 count <200 cell/ul (aOR 3.1; 95%CI 1.6-6.0)
      were associated with increased risk of having anemia while a BMI >=30 kg/m2 (aOR
      0.8; 95% CI 0.6-1.0) and being on ART for more than 10 years (aOR 0.4; 95% CI 0.2
      0.9) were associated with reduced risk of anemia. Being on a zidovudine-
      containing ART regimen was not associated with anemia. CONCLUSION: Anemia is
      common in people on second line ART in Lilongwe, Malawi. Screening for anemia in
      this population would be a useful strategy; especially for female patients, those
      who are underweight and have a low CD4 cell counts.

PMID- 29334933
TI  - Temporary exclusion of ill children from childcare centres in Switzerland:
      practice, problems and potential solutions.
AB  - BACKGROUND: In childcare centres, temporary exclusion of ill children, if their
      illness poses a risk of spread of harmful diseases to others, is a central
      approach to fight disease transmission. However, not all ill children need to be
      excluded. Previous studies suggested that childcare centre staff have
      difficulties in deciding whether or not to exclude an ill child, even when
      official ill-child guidelines are used. We aimed to describe, quantify and
      analyse these ambiguities and discuss potential solutions. METHODS: For this
      cross-sectional study, we sent postal surveys to 488 childcare centre directors
      in the Swiss Canton of Zurich, where no official ill-child guideline is in place.
      We asked for exclusion criteria for ill children and ambiguities faced when
      dealing with ill children. We checked whether existing guidelines provided
      solutions to the ambiguities identified. RESULTS: 249/488 (51%) directors
      responded to the survey. The most common exclusion criteria were fever (87.4%)
      and contagiousness (52.2%). Ambiguities were mostly caused by conjunctivitis
      (23.7%) and use of antipyretic drugs (22.9%). Roughly one third of the
      ambiguities identified could have been resolved with existing guidelines, another
      third if existing guidelines contained additional information. For the last
      third, clear written directives are difficult to formulate. CONCLUSIONS: Written
      recommendations may help to clarify when an ill child should temporarily be
      excluded. However, such a guideline should cover the topics antipyretic drugs and
      teething and have room for modification to local circumstances. Collaboration
      with a paediatrician may be of additional benefit.

PMID- 29334934
TI  - Factors influencing the length of hospital stay of patients with anorexia nervosa
      - results of a prospective multi-center study.
AB  - BACKGROUND: The length of stay (LOS) strongly influences anorexia nervosa (AN)
      inpatient weight outcomes. Hence, understanding the predictors of LOS is highly
      relevant. However, the existing evidence is inconsistent and to draw conclusions,
      additional evidence is required. METHODS: We conducted a prospective, multi
      center study including adult female inpatients with AN. Using stepwise linear
      regression, the following demographic and clinical variables were examined as
      potential predictors for LOS: admission BMI, AN-subtype, age, age of onset,
      living situation, partnership status, education, previous hospitalization, self
      rated depression, anxiety and somatic symptoms (PHQ-9, PHQ-15, GAD-7), self-rated
      therapy motivation (FEVER) and eating disorder psychopathology (EDI-2 subscale
      scores). RESULTS: The average LOS of the sample (n = 176) was 11.8 weeks (SD =
      5.2). Longer LOS was associated with lower admission BMI (beta = -1.66; p <
      .001), purging AN-subtype (beta = 1.91; p = .013) and higher EDI-2 asceticism
      (beta = 0.12; p = .030). Furthermore, differences between treatment sites were
      evident. CONCLUSIONS: BMI at admission and AN-subtype are routinely assessed
      variables, which are robust and clinically meaningful predictors of LOS. Health
      care policies might consider these variables. In light of the differences between
      treatment sites future research on geographical variations in mental health care
      seems recommended.

PMID- 29334935
TI  - Adoption and diffusion of zoning bylaws banning fast food drive-through services
      across Canadian municipalities.
AB  - BACKGROUND: Healthy public policy is an important tool for creating environments
      that support human health and wellbeing. At the local level, municipal policies,
      such as zoning bylaws, provide an opportunity for governments to regulate
      building location and the type of services offered. Across North America, there
      has been a recent proliferation of municipal bylaws banning fast food drive
      through services. Research on the utilization of this policy strategy, including
      bylaw adopters and adopter characteristics, is limited within the Canadian
      context. The aim of this study was to identify and characterize Canadian
      municipalities based on level of policy innovation and nature of their adopted
      bylaw banning fast food drive-through services. METHODS: A multiple case history
      methodology was utilized to identify and analyse eligible municipal bylaws, and
      included development of a chronological timeline and map of adopter
      municipalities within Canada. Grey literature and policy databases were searched
      for potential adopters of municipal fast food drive-through service bylaws.
      Adopters were confirmed through evidence of current municipal bylaws. Geographic
      diffusion and diffusion of innovations theories provided a contextual framework
      for analysis of bylaw documents. Analysis included assignment of adopter-types,
      extent and purpose of bans, and policy learning activities of each adopter
      municipality. RESULTS: From 2002 to 2016, 27 municipalities were identified as
      adopters: six innovators and twenty-one early adopters. Mapping revealed parallel
      geographic diffusion patterns in western and eastern Canada. Twenty-two
      municipalities adopted a partial ban and five adopted a full ban. Rationales for
      the drive-through bans included health promotion, environmental concerns from
      idling, community character and aesthetics, traffic concerns, and walkability.
      Policy learning, including research and consultation with other municipalities,
      was performed by nine early adopters. CONCLUSION: This study detailed the
      adoption of fast food drive-through bylaws across Canada. Understanding the
      adopter-type characteristics of municipalities and the nature of their bylaws can
      assist other jurisdictions in similar policy efforts. While the implications for
      research and practice are evolving and dynamic, fast food drive-through service
      bans may play a role in promoting healthier food environments. Further research
      is required to determine the viability of this strategy for health promotion and
      chronic disease prevention.

PMID- 29334936
TI  - Gender-based violence screening methods preferred by women visiting a public
      hospital in Pune, India.
AB  - BACKGROUND: Gender-based violence (GBV) is a major global public health concern
      and is a risk factor for adverse health outcomes. Early identification of GBV is
      crucial for improved health outcomes. Interactions with health care providers may
      provide a unique opportunity for routine GBV screening, if a safe, confidential
      environment can be established. METHODS: Between November 2014 and February 2015,
      a cross-sectional, observational study was conducted where women were interviewed
      about their opinions concerning GBV screening in a tertiary health care setting
      in Pune, India. Trained counsellors interviewed 300 women at different out
      patient and in-patient departments using a semi-structured questionnaire.
      RESULTS: Twenty-three percent of these women reported experiencing GBV in their
      life. However, 90% of women said they had never been asked about GBV in a health
      care setting. Seventy-two percent expressed willingness to be asked about GBV by
      their health care providers, with the preferred provider being nurses or
      counsellors. More than half (53%) women reported face-to-face interview as the
      most preferred method for screening. There were no major differences in these
      preferences by GBV history status. CONCLUSIONS: Our study provides evidence for
      preferred GBV screening methods and optimal provider engagement as perceived by
      women attending a public hospital.

PMID- 29334937
TI  - Perspectives on setting limits for RF contact currents: a commentary.
AB  - BACKGROUND: Limits for exposure to radiofrequency (RF) contact currents are
      specified in the two dominant RF safety standards and guidelines developed by the
      Institute of Electrical and Electronics Engineers (IEEE) and the International
      Commission on Non-Ionizing Radiation Protection (ICNIRP). These limits are
      intended to prevent RF burns when contacting RF energized objects caused by high
      local tissue current densities. We explain what contact currents are and review
      some history of the relevant limits with an emphasis on so-called "touch"
      contacts, i.e., contact between a person and a contact current source during
      touch via a very small contact area. RESULTS: Contact current limits were
      originally set on the basis of controlling the specific absorption rate resulting
      from the current flowing through regions of small conductive cross section within
      the body, such as the wrist or ankle. More recently, contact currents have been
      based on thresholds of perceived heating. In the latest standard from the IEEE
      developed for NATO, contact currents have been based on two research studies in
      which thresholds for perception of thermal warmth or thermal pain have been
      measured. Importantly, these studies maximized conductive contact between the
      subject and the contact current source. This factor was found to dominate the
      response to heating wherein high resistance contact, such as from dry skin, can
      result in local heating many times that from a highly conductive contact. Other
      factors such as electrode size and shape, frequency of the current and the
      physical force associated with contact are found to introduce uncertainty in
      threshold values when comparing data across multiple studies. CONCLUSIONS:
      Relying on studies in which the contact current is minimized for a given
      threshold does not result in conservative protection limits. Future efforts to
      develop limits on contact currents should include consideration of (1) the basis
      for the limits (perception, pain, tissue damage); (2) understanding of the
      practical conditions of real world exposure for contact currents such as contact
      resistance, size and shape of the contact electrode and applied force at the
      point of contact; (3) consistency of how contact currents are applied in research
      studies across different researchers; (4) effects of frequency.

PMID- 29334938
TI  - Therapeutic plasma exchange in a tertiary care center: 185 patients undergoing
      912 treatments - a one-year retrospective analysis.
AB  - BACKGROUND: Therapeutic plasma exchange (TPE) is increasingly used throughout the
      world. Although the procedure itself is fairly standardized, it is yet unknown
      how the underlying disease entities influence the key coordinates of the
      treatment. METHODS: Retrospective chart review. The treatment indications were
      clustered into four categories. Data are presented as median and interquartile
      (25-75%) range [IQR]. RESULTS: Within 1 year, 912 TPE treatments were performed
      in 185 patients (90 female, 48.6%). The distribution of the treatment numbers to
      the pre-specified disease categories were as follows: transplantation (35.7%),
      neurology (31.9%), vasculitis and immunological disease (17.3%), and others
      including thrombotic microangiopathy (8.1%), critical care related diseases
      (5.4%), hematology [multiple myeloma] (1.1%), and endocrine disorders (0.5%). The
      calculated plasma volume was significantly higher in patients with vasculitis and
      immunological diseases (3984 [3433-4439] ml) as compared to patients treated for
      transplant related indications (3194 [2545-3658] ml; p = 0.0003) and neurological
      diseases (3058 [2533-3359] ml; p < 0.0001). This was mainly due to the
      differences in the hematocrit which was 30.5 [27.0-33.6] % in the
      vasculitis/immunological disease patients and 40.2 [37.5-42.9] % in the
      neurological patients; p < 0.0001. Interestingly, treatment time using a membrane
      based technology was significantly longer than TPE using a centrifugal device
      135.0 [125.0-140.0] min vs. 120.0 [112.5-135.0] min. Furthermore, the relative
      exchanged plasma volume was significantly lower in the treatment of vasculitis
      and immunological diseases as compared to treatments of transplant related
      indications and neurological diseases. CONCLUSION: Patients with low hematocrit
      and high body weight do not receive the minimum recommended dose of exchange
      volume. Centrifugal TPE allowed faster plasma exchange than membrane TPE.

PMID- 29334939
TI  - Choosing a career in oncology: results of a nationwide cross-sectional study.
AB  - BACKGROUND: Little information is currently available concerning young medical
      students desire to pursue a career in oncology, or their career expectations.
      METHODS: This project is a cross-sectional epidemiological study. A voluntary and
      anonymous questionnaire was distributed to all young oncologists studying in
      France between the 2nd of October 2013 and the 23rd of February 2014. RESULTS:
      The overall response rate was 75.6%. A total of 505 young oncologists completed
      the questionnaire. The main determining factors in the decision to practice
      oncology were the cross-sectional nature of the field (70.8%), the depth and
      variety of human relations (56.3%) and the multi-disciplinary field of work
      (50.2%). Most residents would like to complete a rotation outside of their
      assigned region (59.2%) or abroad (70.2%) in order to acquire additional
      expertise (67.7%). In addition, most interns would like to undertake a fellowship
      involving care, teaching and research in order to hone their skills (85.7%) and
      forge a career in public hospitals (46.4%). Career prospects mainly involve
      salaried positions in public hospitals. Many young oncologists are concerned
      about their professional future, due to the shortage of openings (40.8%), the
      workload (52.8%) and the lack of work-life balance (33.4%). CONCLUSIONS: This
      investigation provides a comprehensive profile of the reasons young oncologists
      chose to pursue a career in oncology, and their career prospects.

PMID- 29334940
TI  - Correction to: The transcriptome landscape of early maize meiosis.
AB  - CORRECTION: Following publication of the original article [1], the authors
      reported that the number of genes overlaying the bar graph in Fig. 3A were
      incorrectly counted and inserted (i.e. including a title tile, and in inverse
      order). The corrected numbers are below and match with the listed genes supplied
      in Additional File: Table S2.

PMID- 29334941
TI  - The association of the N-terminal pro-brain-type natriuretic peptide response to
      exercise with disease severity in therapy-naive pulmonary arterial hypertension:
      a cohort study.
AB  - BACKGROUND: While the N-terminal pro-brain-type natriuretic peptide (NT-proBNP)
      at rest is known to be associated with prognosis in pulmonary arterial
      hypertension (PAH), it is unclear if the NT-proBNP response to exercise (DeltaNT
      proBNP) can contribute to a better assessment of disease severity. METHODS: We
      investigated the association of NT-proBNP values at rest and during peak exercise
      with hemodynamics and cardiopulmonary exercise testing parameters in 63 therapy
      naive PAH patients. RESULTS: The median NT-proBNP increases from 1414 at rest to
      1500 pg/ml at peak exercise. The DeltaNT-proBNP is baseline-dependent in PAH.
      Both, NT-proBNP at rest and NT-proBNP at peak exercise, are significantly
      correlated with hemodynamics and functional capacity. However, neither NT-proBNP
      at peak exercise nor DeltaNT-proBNP correlated better with surrogate markers of
      disease severity than NT-proBNP at rest. CONCLUSION: The DeltaNT-proBNP does not
      contribute to a better assessment of disease severity in PAH.

PMID- 29334942
TI  - Poor response to artesunate treatment in two patients with severe malaria on the
      Thai-Myanmar border.
AB  - BACKGROUND: Malaria has declined dramatically along the Thai-Myanmar border in
      recent years due to malaria control and elimination programmes. However, at the
      same time, artemisinin resistance has spread, raising concerns about the efficacy
      of parenteral artesunate for the treatment of severe malaria. CASE PRESENTATION:
      In November 2015 and April 2017, two patients were treated for severe malaria
      with parenteral artesunate. Quinine was added within 24 h due to an initial poor
      response to treatment. The first patient died within 24 h of starting treatment
      and the second did not clear his peripheral parasitaemia until 11 days later.
      Genotyping revealed artemisinin resistance Kelch-13 markers. CONCLUSIONS:
      Reliable efficacy of artesunate for the treatment of severe malaria may no longer
      be assured in areas where artemisinin resistance has emerged. Empirical addition
      of parenteral quinine to artesunate for treatment is recommended as a
      precautionary measure.

PMID- 29334943
TI  - Training programmes to improve evidence uptake and utilisation by
      physiotherapists: a systematic scoping review.
AB  - BACKGROUND: Research training programmes are a knowledge translation (KT)
      intervention which aim to improve research evidence uptake by clinicians. Whilst
      KT training programmes have been reported to significantly improve evidence
      uptake by physiotherapists, it is unclear which aspects of training optimally
      assist KT into physiotherapy practice. The purpose of the review was to establish
      the body of evidence regarding KT training programmes to improve
      physiotherapists' use of evidence-based practice (EBP) and clinical practice
      guidelines (CPG). METHODS: A systematic scoping review was undertaken in line
      with the adapted Arksey and O'Malley framework. Nine electronic databases
      (CINAHL, BIOMED CENTRAL, Cochrane, Web of Science, PROQUEST, PUBMED, OTseeker,
      Scopus, ERIC) were searched. Targeted keywords identified primary research
      articles of any hierarchy, that described the nature and impact of KT training
      programmes for physiotherapists. Where systematic reviews were identified, the
      component primary studies were considered individually for relevance. Critical
      appraisal was not undertaken due to the nature of a scoping review, and data was
      reported descriptively. RESULTS: Ten systematic reviews were identified (yielding
      four relevant primary studies). Five additional primary studies were identified
      (two randomised controlled trials, two non-randomised controlled trials and one
      pre-post study) which were not included in the original systematic reviews. This
      provided nine eligible primary research studies for review. The KT strategies
      were all multi-faceted. Interactive sessions, didactic sessions, printed material
      and discussion and feedback were consistently associated with effective outcomes.
      When KT strategies addressed local barriers to EBP utilisation, there were better
      success rates for EBP and CPG uptake, irrespective of the outcome measures used.
      There were no consistent ways of measuring outcome. CONCLUSION: Multi-faceted KT
      strategies designed to address local barriers to knowledge translation were most
      effective in improving EBP/ CPG uptake among physiotherapists.

PMID- 29334944
TI  - Changes in malaria epidemiology in Germany, 2001-2016: a time series analysis.
AB  - BACKGROUND: German surveillance data showed a sharp rise of malaria cases in 2014
      and 2015 due to the increased arrival of refugees from malaria endemic countries.
      A time series analysis of data from 2001 to 2016 was performed in order to
      describe the epidemiology of imported malaria in Germany in general and of the
      recent increase in particular. RESULTS: In total, 11,678 malaria cases were
      notified between 2001 and 2016 (range 526-1063 cases/year). Newly arriving
      refugees averaged 10 cases/year (1.5%) in 2001-13 and 292.5 cases/year (28.3%) in
      2014-15. Plasmodium (P.) falciparum was the most frequently reported species
      (range 57.2-85.8%), followed by P. vivax (range during 2001-2013: 7.6-18.1%;
      during 2014-2015, mean 31.3%). In 2014-15, 22.3% of all P. vivax cases were
      refugees from Eritrea and 3.3% from other countries of the Horn of Africa; in
      2015 and 2016, 19.5% were refugees from Afghanistan and Pakistan. Five P.
      knowlesi malaria infections were reportedly acquired in Thailand between 2012 and
      2016. Total numbers of malaria notifications among native Germans and residents
      with migration background showed an increasing trend since 2007. Chemoprophylaxis
      use was reported for 24.3% (1695/6984) of cases and showed a declining trend.
      Native German cases took significantly more frequently chemoprophylaxis than
      cases with migration background (32.6% vs. 17.9%; p < 0.001).
      DISCUSSION/CONCLUSIONS: The steep rise in vivax malaria notifications in 2014 and
      2015 was mainly due to newly arriving refugees from Eritrea but also from other
      countries of the Horn of Africa and South Asia. Clinicians should include malaria
      in their differential diagnosis in case of a febrile illness in the respective
      population and consider vivax malaria even if arrival to Germany dates back
      several months. Over the past 10 years, malaria notifications among native
      Germans and residents with migration background showed an increasing trend. Use
      of chemoprophylaxis was insufficient in both groups and deteriorating. New
      strategies need to be found to increase compliance to chemoprophylaxis
      recommendations. The surveillance provides valuable data for epidemiological
      assessment of imported malaria in Germany.

PMID- 29334946
TI  - Surmounting difficulties to provide home based neonatal care - reflections of
      community health workers.
AB  - BACKGROUND: In India, community health workers' (CHW) effectiveness in providing
      home-based neonatal care (HBNC) has been well documented. The nature of
      challenges faced and strategies adopted while providing HBNC services need to be
      studied in-depth. METHODS: A qualitative study to understand the challenges faced
      and strategies used by Sakhis (women CHW) while providing services as part of a
      HBNC program implemented by a non-profit organization. Data consisted of 20 in
      depth interviews and three focus group discussions (FGD) with Sakhis. RESULTS:
      Sakhis negotiated with the community to start working as a CHW. They faced
      challenges while changing behaviors at individual level and also while bringing
      about a change in harmful normative practices that increased chances of maternal
      and neonatal mortality. Managing crises at the time of deliveries and
      facilitating a safe delivery was the most critical challenge faced by many
      Sakhis. The key strategies used by Sakhis included: proactively and persistently
      providing services even when they faced resistance from the woman or her family;
      evolving contextually suitable counseling techniques and tactics to bring about
      behavioral change; balancing compliance to traditional practices and promoting
      HBNC; defying traditional practices and assisting the woman in times of an
      emergency to save lives. Having on-call support from supervisors and cultivating
      a good working relationship with health providers facilitated effective service
      provision by Sakhis. CONCLUSION: CHWs having a strong sense of commitment can
      develop strategies to address challenges and provide HBNC services effectively if
      they also have strong supervisory support.

PMID- 29334945
TI  - Blood pressure change does not associate with Center of Pressure movement after
      postural transition in geriatric outpatients.
AB  - BACKGROUND: Orthostatic hypotension (OH), a blood pressure drop after postural
      change, is associated with impaired standing balance and falls in older adults.
      This study aimed to assess the association between blood pressure (BP) and a
      measure of quality of standing balance, i.e. Center of Pressure (CoP) movement,
      after postural change from supine to standing position in geriatric outpatients,
      and to compare CoP movement between patients with and without OH. METHODS: In a
      random subgroup of 75 consecutive patients who were referred to a geriatric
      outpatient clinic, intermittent BP measurements were obtained simultaneously with
      CoP measurements in mediolateral and anterior-posterior direction directly after
      postural change during 3 min of quiet stance with eyes open on a force plate.
      Additional measurements of continuous BP were available in n = 38 patients.
      Associations between BP change during postural change and CoP movement were
      analyzed using Spearman correlation. Mann-Whitney-U tests were used to compare
      CoP movement between patients with OH and without OH, in which OH was defined as
      a BP drop exceeding 20 mmHg of systolic BP (SBP) and/or 10 mmHg of diastolic BP
      (DBP) within 3 min after postural change. RESULTS: OH measured intermittently was
      found in 8 out of 75 (11%) and OH measured continuously in 22 out of 38 patients
      (57.9%). BP change did not associate with CoP movement. CoP movement did not
      differ significantly between patients with and without OH. CONCLUSIONS: Results
      do not underpin the added value of CoP movement measurements in diagnosing OH in
      a clinical setting. Neither could we identify the role of CoP measurements in the
      understanding of the relation between OH and impaired standing balance.

PMID- 29334948
TI  - Molecular identification and investigations of contagious ecthyma (Orf virus) in
      small ruminants, North west Ethiopia.
AB  - BACKGROUND: Orf virus, the prototype of parapoxvirus, is the main causative agent
      of contagious ecthyma. Little is known about the status of the disease in
      Ethiopia and this study was aimed at determining its status using PCR as a
      confirmatory tool. METHODS: a total of 400 randomly selected sheep and goat was
      screened for the identification of the virus using amplification of B2L gene and
      transfection of mammalian cells (VERO cells). RESULTS: Out of 400 animals
      screened for infection of the virus, 48 animals were found positive to PCR and
      revealed an overall incidence of 12%. Different epidemiological parameters were
      considered to look at the association with incidence of the disease and of which,
      only species of the animal(sheep), non-vaccinated and non-treated animals,
      nursing animals, poor body condition animals, extensively managed animals,
      animals having mouth lesion, and study areas having outbreak history showed
      higher prevalence. A univariate logistic regression analysis showed statistically
      significant difference in all variables (P < 0.05). Whereas, age and sex of
      animals showed no significant difference (P < 0.05). CONCLUSION: The result of
      the present finding showed high incidence of Orf virus in the region as confirmed
      through PCR.

PMID- 29334947
TI  - Effects of hypoxia and hyperoxia on the differential expression of VEGF-A
      isoforms and receptors in Idiopathic Pulmonary Fibrosis (IPF).
AB  - Dysregulation of VEGF-A bioavailability has been implicated in the development of
      lung injury/fibrosis, exemplified by Idiopathic Pulmonary Fibrosis (IPF). VEGF-A
      is a target of the hypoxic response via its translational regulation by HIF
      1alpha. The role of hypoxia and hyperoxia in the development and progression of
      IPF has not been explored. In normal lung (NF) and IPF-derived fibroblasts (FF)
      VEGF-Axxxa protein expression was upregulated by hypoxia, mediated through
      activation of VEGF-Axxxa gene transcription. VEGF-A receptors and co-receptors
      were differentially expressed by hypoxia and hyperoxia. Our data supports a
      potential role for hypoxia, hyperoxia and VEGF-Axxxa isoforms as drivers of
      fibrogenesis.

PMID- 29334949
TI  - Flaxseed-enriched diets change milk concentration of the antimicrobial
      danofloxacin in sheep.
AB  - BACKGROUND: Flaxseed is the most common and rich dietary source of lignans and is
      an acceptable supply of energy for livestock. Flaxseed lignans are precursors of
      enterolignans, mainly enterolactone and enterodiol, produced by the rumen and
      intestinal microbiota of mammals and have many important biological properties as
      phytoestrogens. Potential food-drug interactions involving flaxseed may be
      relevant for veterinary therapy, and for the quality and safety of milk and dairy
      products. Our aim was to investigate a potential food-drug interaction involving
      flaxseed, to explore whether the inclusion of flaxseed in sheep diet affects
      concentration of the antimicrobial danofloxacin in milk. RESULTS: Increased
      concentrations of enterodiol and enterolactone were observed in sheep plasma and
      milk after 2 weeks of flaxseed supplementation (P < 0.05). However, enterolactone
      and enterodiol conjugates were not detected in milk. Milk danofloxacin
      pharmacokinetics showed that area under the curve (AUC)0-24, maximum
      concentration (Cmax) and AUC0-24 milk-to-plasma ratios were reduced by 25-30% in
      sheep fed flaxseed-enriched diets (P < 0.05). Our results demonstrate, therefore,
      that flaxseed-enriched diets reduce the amount of danofloxacin in sheep milk and
      enrich the milk content of lignan-derivatives. CONCLUSION: These findings
      highlight an effect of flaxseed-enriched diets on the concentration of
      antimicrobials in ruminant's milk, revealing the potential of these modified
      diets for the control of residues of antimicrobial drugs in milk.

PMID- 29334950
TI  - Will human influences on evolutionary dynamics in the wild pervade the
      Anthropocene?
AB  - The five most pervasive anthropogenic threats to biodiversity are over
      exploitation, habitat changes, climate change, invasive species, and pollution.
      Since all of these threats can affect intraspecific biodiversity-including
      genetic variation within populations-humans have the potential to induce
      contemporary microevolution in wild populations. We highlight recent empirical
      studies that have explored the effects of these anthropogenic threats to
      intraspecific biodiversity in the wild. We conclude that it is critical that we
      move towards a predictive framework that integrates a better understanding of
      contemporary microevolution to multiple threats to forecast the fate of natural
      populations in a changing world.

PMID- 29334951
TI  - The surprising implications of familial association in disease risk.
AB  - BACKGROUND: A wide range of diseases show some degree of clustering in families;
      family history is therefore an important aspect for clinicians when making risk
      predictions. Familial aggregation is often quantified in terms of a familial
      relative risk (FRR), and although at first glance this measure may seem simple
      and intuitive as an average risk prediction, its implications are not
      straightforward. METHODS: We use two statistical models for the distribution of
      disease risk in a population: a dichotomous risk model that gives an intuitive
      understanding of the implication of a given FRR, and a continuous risk model that
      facilitates a more detailed computation of the inequalities in disease risk.
      Published estimates of FRRs are used to produce Lorenz curves and Gini indices
      that quantifies the inequalities in risk for a range of diseases. RESULTS: We
      demonstrate that even a moderate familial association in disease risk implies a
      very large difference in risk between individuals in the population. We give
      examples of diseases for which this is likely to be true, and we further
      demonstrate the relationship between the point estimates of FRRs and the
      distribution of risk in the population. CONCLUSIONS: The variation in risk for
      several severe diseases may be larger than the variation in income in many
      countries. The implications of familial risk estimates should be recognized by
      epidemiologists and clinicians.

PMID- 29334952
TI  - Predictors of overweight/obesity in a Brazilian cohort after 13 years of follow
      up.
AB  - BACKGROUND: Obesity is a chronic complex disease with an increasing prevalence
      around the world. Prospective studies in adult cohorts are needed to provide
      information about predictors of new-onset overweight/obesity on population-based
      levels. The aim of this study was to identify factors associated with the risk of
      an adult individual become overweight/obese after 13 years of follow-up. METHODS:
      Second phase of an observational population-based prospective cohort study in a
      small town in the Midwest region of Brazil. A representative sample of the adult
      population (>=18 years) was assessed in 2002 (phase 1). Anthropometric,
      sociodemographic, dietary intake and lifestyle data were collected. After 13
      years of follow-up (2015), the same variables were re-evaluated (phase 2). New
      onset overweight/obesity was the outcome variable. RESULTS: A total of 685
      subjects were included with a mean age in phase 1 of 42.7 +/- 13.8 years and 56.1
      +/- 13.8 years in phase 2, the mean follow-up time was 13.2 years and female sex
      counted for 66.3% of the sample. Total weight gain was 5.9 +/- 10.2 Kg, body mass
      index increased 2.6 +/- 3.8 Kg/m2 and waist circumference (WC) values increased
      8.0 +/- 10.5 cm. The prevalence of overweight/obesity went from 49.1% in phase 1
      to 69.8% in phase 2 (p < 0.001). The factors associated with a decreased risk of
      new-onset overweight/obesity were ages between 50 and 64 (RR 0.40; CI 0.24-0.67 -
      p = 0.001) and >=65 years (RR 0.15; CI 0.06-0.35 - p < 0.001), being part of the
      second quartile of fat consumption (RR 0.59; CI 0.35-0.97 - p = 0.041), no
      alcohol consumption (RR 0.59; CI 0.37-0.93 - p = 0.024) and smoking (RR 0.58; CI
      0.39-0.86 - p = 0,007) in phase 1. CONCLUSIONS: We identified in thirteen years
      of follow-up that older ages, a moderate fat consumption compared to low
      consumption, no alcohol consumption and smoking habit were related to a decreased
      risk of new-onset overweight/obesity. Obesity prevention actions must focus on
      subjects at younger ages and include policies to reduce alcohol consumption.

PMID- 29334953
TI  - Care relationships at stake? Home healthcare professionals' experiences with
      digital medicine dispensers - a qualitative study.
AB  - BACKGROUND: Although digital technologies can mitigate the burdens of home
      healthcare services caused by an ageing population that lives at home longer with
      complex health problems, research on the impacts and consequences of digitalised
      remote communication between patients and caregivers is lacking. The present
      study explores how home healthcare professionals had experienced the introduction
      of digital medicine dispensers and their influence on patient-caregiver
      relationships. METHODS: The multi-case study comprised semi-structured interviews
      with 21 healthcare professionals whose home healthcare service involved using the
      digital medicine dispensers. The constant comparative method was used for data
      analyses. RESULTS: Altogether, interviewed healthcare professionals reported
      three main technology-related impacts upon their patient-caregiver relationships.
      First, national and local pressure to increase efficiency had troubled their
      relationships with patients who suspected that municipalities have sought to
      lower costs by reducing and digitalising services. Participants reported having
      to consider such worries when introducing technologies into their services.
      Second, participants reported a shift towards empowering patients. Digital
      technology can empower patients who value their independence, whereas safety is
      more important for other patients. Healthcare professionals needed to ensure that
      replacing care tasks with technology implies safe and improved care. Third, the
      safety and quality of digital healthcare services continues to depend upon
      surveillance and control mechanisms that compensate for less face-to-face
      monitoring. Participants did not consider the possibility that surveillance
      exposes information about patients' everyday lives to be problematic, but to
      constitute opportunities for adjusting services to meet patients' needs.
      CONCLUSIONS: Technologies such as digital medicine dispensers can improve the
      efficiency of healthcare services and enhance patients' independence when
      introduced in a way that empowers patients as well as safeguards trust and
      service quality. Conversely, the patient-caregiver relationship can suffer if the
      technology does not meet patients' needs and fails to offer safe and trustworthy
      services. Upon introducing technology, home healthcare professionals therefore
      need to carefully consider the benefits and possible disadvantages of the
      technology. Ethical implications for both individuals and societies need to be
      further discussed.

PMID- 29334954
TI  - Association between non-cholesterol sterol concentrations and Achilles tendon
      thickness in patients with genetic familial hypercholesterolemia.
AB  - BACKGROUND: Familial hypercholesterolemia (FH) is a genetic disorder that result
      in abnormally high low-density lipoprotein cholesterol levels, markedly increased
      risk of coronary heart disease (CHD) and tendon xanthomas (TX). However, the
      clinical expression is highly variable. TX are present in other metabolic
      diseases that associate increased sterol concentration. If non-cholesterol
      sterols are involved in the development of TX in FH has not been analyzed.
      METHODS: Clinical and biochemical characteristics, non-cholesterol sterols
      concentrations and Aquilles tendon thickness were determined in subjects with
      genetic FH with (n = 63) and without (n = 40) TX. Student-t test o Mann-Whitney
      test were used accordingly. Categorical variables were compared using a Chi
      square test. ANOVA and Kruskal-Wallis tests were performed to multiple
      independent variables comparison. Post hoc adjusted comparisons were performed
      with Bonferroni correction when applicable. Correlations of parameters in
      selected groups were calculated applying the non-parametric Spearman correlation
      procedure. To identify variables associated with Achilles tendon thickness
      changes, multiple linear regression were applied. RESULTS: Patients with TX
      presented higher concentrations of non-cholesterol sterols in plasma than
      patients without xanthomas (P = 0.006 and 0.034, respectively). Furthermore,
      there was a significant association between 5alpha-cholestanol, beta-sitosterol,
      desmosterol, 24S-hydroxycholesterol and 27-hydroxycholesterol concentrations and
      Achilles tendon thickness (p = 0.002, 0.012, 0.020, 0.045 and 0.040,
      respectively). CONCLUSIONS: Our results indicate that non-cholesterol sterol
      concentrations are associated with the presence of TX. Since cholesterol and non
      cholesterol sterols are present in the same lipoproteins, further studies would
      be needed to elucidate their potential role in the development of TX.

PMID- 29334955
TI  - The inverted cup device for blood transfer on malaria RDTs: ease of use,
      acceptability and safety in routine use by health workers in Nigeria.
AB  - BACKGROUND: Malaria rapid diagnostic tests (RDTs) are becoming widely adopted for
      case management at community level. However, reports and anecdotal observations
      indicate that the blood transfer step poses a significant challenge to many
      users. This study sought to evaluate the inverted cup device in the hands of
      health workers in everyday clinical practice, in comparison with the plastic
      pipette, and to determine the volume accuracy of the device made of a lower-cost
      plastic. METHODS: The volume accuracy of inverted cup devices made of two
      plastics, PMMA and SBC, was compared by transferring blood 150 times onto filter
      paper and comparing the blood spot areas with those produced by 20 reference
      transfers with a calibrated micropipette. The ease of use, safety and
      acceptability of the inverted cup device and the pipette were evaluated by 50
      health workers in Nigeria. Observations were recorded on pre-designed
      questionnaires, by the health workers themselves and by trained observers. Focus
      group discussions were also conducted. RESULTS: The volume accuracy assessment
      showed that the device made from the low-cost material (SBC) delivered a more
      accurate volume (mean 5.4 MUL, SD 0.48 MUL, range 4.5-7.0 MUL) than the PMMA
      device (mean 5.9 MUL, SD 0.48 MUL, range 4.9-7.2 MUL). The observational
      evaluation demonstrated that the inverted cup device performed better than the
      pipette in all aspects, e.g. higher proportions of health workers achieved
      successful blood collection (96%, vs. 66%), transfer of the required blood volume
      (90%, vs. 58%), and blood deposit without any loss (95%, vs. 50%). Majority of
      health workers also considered it' very easy' to use (81%),'very appropriate' for
      everyday use (78%), and 50% of them reported that it was their preferred BTD.
      CONCLUSIONS: The good volume accuracy and high acceptability of the inverted cup
      device shown in this study, along with observed ease of use and safety in hands
      of health workers, further strengthens prior findings which demonstrated its
      higher accuracy as compared with other BTDs in a laboratory setting. Altogether,
      these studies suggest that the inverted cup device should replace other types of
      devices for use in day-to-day malaria diagnosis with RDTs.

PMID- 29334956
TI  - Identification and characterization of areas of high and low risk for
      asymptomatic malaria infections at sub-village level in Ratanakiri, Cambodia.
AB  - BACKGROUND: Malaria elimination needs a concentration of activities towards
      identification of residual transmission foci and intensification of efforts to
      eliminate the last few infections, located in so-called 'malaria hotspots'.
      Previous work on characterizing malaria transmission hotspots has mainly focused
      on falciparum malaria and especially on symptomatic cases, while the malaria
      reservoir is expected to be mainly concentrated in the asymptomatic human
      population when transmission is low. For Plasmodium vivax, there has been less
      effort in identifying transmission hotspots. The main aim of this study was to
      uncover micro-epidemiological mechanisms of clustering of malaria infections at a
      sub-village level, based on geographical or behavioural features. METHODS: A
      cross-sectional survey was performed in three villages within the highest malaria
      endemic province of Cambodia. The survey took place in the dry season, when the
      malaria reservoir is expected to be low and residing in the asymptomatic part of
      the population. Village and field locations of households were georeferenced,
      blood samples were taken from as many residents as possible and a short
      questionnaire probing for individual risk factors was taken. Asymptomatic malaria
      carriers were detected by PCR, and geographical clustering analysis (SaTScan) as
      well as risk factor analysis were performed. RESULTS: A total of 1540 out of 1792
      (86%) individuals were sampled. Plasmodial DNA was detected in 129 individuals
      (8.4%). P. vivax was most prevalent (5.5%) followed by Plasmodium malariae (2.1%)
      and Plasmodium falciparum (1.6%). Mixed infection occurred in 12 individuals. In
      two out of three villages geographical clustering of high and low malaria
      infection risk was clearly present. Cluster location and risk factors associated
      with the infection differed between the parasite species. Age was an important
      risk factor for the combined Plasmodium infections, while watching television at
      evenings was associated with increased odds of P. vivax infections [OR (CI): 1.86
      (0.95-3.64)] and bed net use was associated with reduced odds of P. falciparum
      infections [OR (CI): 0.25 (0.077-0.80)]. CONCLUSIONS: Clusters of malaria
      carriers were malaria species specific and often located remotely, outside
      village centres. As such, at micro-epidemiological level, malaria is not a single
      disease. Further unravelling the micro-epidemiology of malaria can enable
      programme managers to define the interventions likely to contribute to halt
      transmission in a particular hotspot location.

PMID- 29334957
TI  - Vertebral column decancellation in Pott's deformity: use of Surgimap Spine for
      preoperative surgical planning, retrospective review of 18 patients.
AB  - BACKGROUND: In the late stage of Spinal tuberculosis, the bony destruction and
      vertebral collapse often leads to significant kyphosis, presenting clinically as
      a painful gibbus deformity, with increased instability, vertebral body
      translations and increased risk of neurologic involvement. Vertebral column
      decancellation is thought to be suitable for most patients with severe rigid
      kyphosis. Surgimap Spine, could offer a pragmatic graphical method for the
      surgical planning of osteotomies. The aim of this study was to evaluate the
      efficacy of Vertebral column decancellation planned preoperatively with the
      computer software-assistance in the patients with Pott's kyphosis. METHODS:
      Between May 2012 and May 2015, 18 patients with Pott's kyphosis underwent the
      Vertebral column decancellation using Surgimap Spine for preoperative surgical
      planning. Preoperative and postoperative Konstam's angle, sagittal vertical
      angle, lumbar lordosis, thoracic kyphosis, pelvic tilt and pelvic incidence were
      measured. Visual analog scale and American Spinal Injury Association were
      documented. RESULTS: The Konstam's angles decreased from 88.1 degrees  (range, 70
      105 degrees ) preoperatively to 18.5 degrees  (range, 7-31 degrees ) (P < 0.01).
      All patients reached the physiological limits at the final follow-up. The mean
      VAS score was reduced from preoperative 7.1 (range, 6-8) to 1.8 (range, 1-3, P <
      0.01) and the ODI improved from 65.8% (range, 58-74%) to 20.2% (range, 12-38%, P
      < 0.01). At final follow-up, there was radiographic evidence of solid fusion at
      the osteotomy site and fixed segments in all patients. Neurological function
      improved from ASIA scale D to E in 5 patients. The patients were followed up for
      30.4 months on average. CONCLUSION: Vertebral column decancellation is an
      effective treatment option for severe Pott's kyphosis. The surgical planning
      software Surgimap Spine can be a reliable and helpful tool that provides a
      simplified method to evaluate and analyze the spino-pelvic parameters and
      simulate the osteotomy procedure. According to individual character, the
      appropriate surgery strategy should be selected.

PMID- 29334958
TI  - Clinical rationale and safety of restaging transurethral resection in indication
      stratified patients with high-risk non-muscle-invasive bladder cancer.
AB  - BACKGROUND: Indications for restaging transurethral resection of the bladder
      tumor (reTURBT) in patients with non-muscle-invasive bladder cancer (NMIBC)
      remain controversial. This study was aimed at evaluation of clinical value and
      safety of reTURBT in different clinical indications. METHODS: This is a
      retrospective analysis of consecutive 141 patients who underwent TURBT followed
      by reTURBT in years 2011-2015 in a single department. Pathological results and
      surgical complications were analyzed in the whole study cohort and stratified by
      clinical stage (Ta, T1, Tx (no muscle in the specimen)) and grade (low-grade
      (LG), high-grade (HG)) of bladder cancer diagnosed at primary TURBT. RESULTS:
      Full data was available for 132 patients. Residual disease was found in 53
      patients (40.2%) with highest rate for Ta-HG cases (57.1%) followed by T1-HG
      (51.4%), Tx-HG (45.2%), T1-LG (32.1%), and Tx-LG (25.8%). In the multivariate
      analysis, high grade (p = 0.02) was the only independent predictor of residual
      disease. Upstaging to muscle-invasive bladder cancer was noticed in 9 patients
      (6.8%). The rate of grade >= 2 Clavien-Dindo complications (1.5 vs. 5.3%) did not
      differ significantly between TURBT and reTURBT cases. CONCLUSIONS: ReTURBT is a
      safe procedure that remains crucial for therapeutic and staging purposes in
      patients with T1, Tx, or high-grade bladder cancer found in the primary
      resection.

PMID- 29334959
TI  - A structural equation model of perceived and internalized stigma, depression, and
      suicidal status among people living with HIV/AIDS.
AB  - BACKGROUND: Previous studies have shown positive association between HIV-related
      stigma and depression, suicidal ideation, and suicidal attempt among people
      living with HIV/AIDS (PLWH). But few studies have examined the mechanisms among
      HIV-related stigma, depression, and suicidal status (suicidal ideation and/or
      suicidal attempt) in PLWH. The current study examined the relationships among
      perceived and internalized stigma (PIS), depression, and suicidal status among
      PLWH in Guangzhou, China using structural equation modeling. METHODS: Cross
      sectional study by convenience sampling was conducted and 411 PLWH were recruited
      from the Number Eight People's Hospital from March to June, 2013 in Guangzhou,
      China. Participants were interviewed on their PIS, depressive symptoms, suicidal
      status, and socio-demographic characteristics. PLWH who had had suicidal ideation
      and suicidal attempts since HIV diagnosis were considered to be suicidal.
      Structural equation model was performed to examine the direct and indirect
      associations of PIS and suicidal status. Indicators to evaluate goodness of fit
      of the structural equation model included Chi-square Statistic, Comparative Fit
      Index (CFI), Root Mean Square Error of Approximation (RMSEA), Standardized Root
      Mean Square Residual (SRMR), and Weighted Root Mean Square Residual (WRMR).
      RESULTS: More than one-third (38.4%) of the PLWH had depressive symptoms and
      32.4% reported suicidal ideation and/or attempt since HIV diagnosis. The global
      model showed good model fit (Chi-square value = 34.42, CFI = 0.98, RMSEA = 0.03,
      WRMR = 0.73). Structural equation model revealed that direct pathway of PIS on
      suicidal status was significant (standardized pathway coefficient = 0.21), and
      indirect pathway of PIS on suicidal status via depression was also significant
      (standardized pathway coefficient = 0.24). There was a partial mediating effect
      of depression in the association between PIS and suicidal status. CONCLUSIONS:
      Our findings suggest that PIS is associated with increased depression and the
      likelihood of suicidal status. Depression is in turn positively associated with
      suicidal status and plays a mediating role between PIS and suicidal status.
      Therefore, to reduce suicidal ideation and attempt in PLWH, targeted
      interventions to reduce PIS and improve mental health status of PLWH are
      warranted.

PMID- 29334960
TI  - Arsenic exposure and risk of nonalcoholic fatty liver disease (NAFLD) among U.S.
      adolescents and adults: an association modified by race/ethnicity, NHANES 2005
      2014.
AB  - BACKGROUND: While associated with obesity, the cause of the rapid rise in
      prevalence of nonalcoholic fatty liver disease (NAFLD) in children, which is
      highest among Hispanics, is not well understood. Animal experiments have
      demonstrated that arsenic exposure contributes to liver injury. Our objective was
      to examine the association between arsenic exposure and NAFLD in humans and to
      determine if race/ethnicity modifies the association. METHODS: Urinary inorganic
      arsenic concentrations among those >=12 years in the National Health and
      Nutrition Examination Survey, 2005-2014 were used to assess the cross-sectional
      association with serum alanine aminotransferase (ALT) levels, a marker of liver
      dysfunction. We excluded high alcohol consumers (>4-5 drinks/day; n = 939),
      positive hepatitis B or C (n = 2330), those missing body mass index (n = 100) and
      pregnant women (n = 629) for a final sample of 8518. Arsenic was measured using
      liquid chromatography coupled with mass spectrometry and ALT was measured using
      standard methods. Sampling weights were used to obtain national estimates. Due to
      lack of normality, estimates were log transformed and are presented as geometric
      means. Logistic regression models controlling for age, sex, income, and weight
      category estimate adjusted odd ratios (aOR) of elevated ALT by quartile of
      arsenic and tested for effect modification by race/ethnicity and weight. Elevated
      ALT was defined as >25 IU/L and >22 IU/L for boys and girls <=17 years,
      respectively and >30 IU/L and >19 IU/L for men and women, respectively. RESULTS:
      Among all, aOR of elevated ALT were higher among those in the highest vs. lowest
      arsenic quartile (referent), 1.4 (95% confidence interval [CI]: 1.1, 1.7) with a
      borderline significant interaction (p = 0.07) by race/ethnicity but not weight (p
      = 0.4). In analysis stratified by race/ethnicity, aOR of elevated ALT among those
      in the 4th quartile were higher among Mexican Americans, 2.0 (CI: 1.3, 3.1) and
      non-Hispanic whites only, aOR 1.4 (CI: 1.1, 1.8) despite the fact that obesity
      prevalence was highest among non-Hispanic blacks. CONCLUSIONS: Our findings
      demonstrate a positive association between urinary arsenic exposure and risk of
      NAFLD among U.S. adolescents and adults that is highest among Mexican Americans
      and among those obese, regardless of race/ethnicity.

PMID- 29334961
TI  - Smoke, alcohol and drug addiction and male fertility.
AB  - In recent decades, the decline in human fertility has become increasingly more
      worrying: while therapeutic interventions might help, they are vexing for the
      couple and often burdened with high failure rates and costs. Prevention is the
      most successful approach to fertility disorders in males and females alike. We
      performed a literature review on three of the most common unhealthy habits -
      tobacco, alcohol and drug addiction - and their reported effects on male
      fertility. Tobacco smoking is remarkably common in most first-world countries;
      despite a progressive decline in the US, recent reports suggest a prevalence of
      more than 30% in subjects of reproductive age - a disturbing perspective, given
      the well-known ill-effects on reproductive and sexual function as well as general
      health. Alcohol consumption is often considered socially acceptable, but its
      negative effects on gonadal function have been consistently reported in the last
      30 years. Several studies have reported a variety of negative effects on male
      fertility following drug abuse - a worrying phenomenon, as illicit drug
      consumption is on the rise, most notably in younger subjects. While evidence in
      these regards is still far from solid, mostly as a result of several confounding
      factors, it is safe to assume that cessation of tobacco smoking, alcohol
      consumption and recreational drug addiction might represent the best course of
      action for any couple trying to achieve pregnancy.

PMID- 29334962
TI  - Developing a tablet computer-based application ('App') to measure self-reported
      alcohol consumption in Indigenous Australians.
AB  - BACKGROUND: The challenges of assessing alcohol consumption can be greater in
      Indigenous communities where there may be culturally distinct approaches to
      communication, sharing of drinking containers and episodic patterns of drinking.
      This paper discusses the processes used to develop a tablet computer-based
      application ('App') to collect a detailed assessment of drinking patterns in
      Indigenous Australians. The key features of the resulting App are described.
      METHODS: An iterative consultation process was used (instead of one-off focus
      groups), with Indigenous cultural experts and clinical experts. Regular (weekly
      or more) advice was sought over a 12-month period from Indigenous community
      leaders and from a range of Indigenous and non-Indigenous health professionals
      and researchers. RESULTS: The underpinning principles, selected survey items, and
      key technical features of the App are described. Features include culturally
      appropriate questioning style and gender-specific voice and images; community
      recognised events used as reference points to 'anchor' time periods;
      'translation' to colloquial English and (for audio) to traditional language;
      interactive visual approaches to estimate quantity of drinking; images of
      specific brands of alcohol, rather than abstract description of alcohol type
      (e.g. 'spirits'); images of make-shift drinking containers; option to estimate
      consumption based on the individual's share of what the group drank. CONCLUSIONS:
      With any survey platform, helping participants to accurately reflect on and
      report their drinking presents a challenge. The availability of interactive,
      tablet-based technologies enables potential bridging of differences in culture
      and lifestyle and enhanced reporting.

PMID- 29334963
TI  - Evaluating the impact of a falls prevention community of practice in a
      residential aged care setting: a realist approach.
AB  - BACKGROUND: Falls are a major socio-economic problem among residential aged care
      (RAC) populations resulting in high rates of injury including hip fracture.
      Guidelines recommend that multifactorial prevention strategies are implemented
      but these require translation into clinical practice. A community of practice
      (CoP) was selected as a suitable model to support translation of the best
      available evidence into practice, as it could bring together like-minded people
      with falls expertise and local clinical knowledge providing a social learning
      opportunity in the pursuit of a common goal; falls prevention. The aims of this
      study were to evaluate the impact of a falls prevention CoP on its membership;
      actions at facility level; and actions at organisation level in translating falls
      prevention evidence into practice. METHODS: A convergent, parallel mixed methods
      evaluation design based on a realist approach using surveys, audits, observations
      and semi-structured interviews. Participants were 20 interdisciplinary staff
      nominating as CoP members between Nov 2013-Nov 2015 representing 13 facilities
      (approximately 780 beds) of a RAC organisation. The impact of the CoP was
      evaluated at three levels to identify how the CoP influenced the observed
      outcomes in the varying contexts of its membership (level i.), the RAC facility
      (level ii.) and RAC organisation (level iii.). RESULTS: Staff participating as
      CoP members gained knowledge and awareness in falls prevention (p < 0.001)
      through connecting and sharing. Strategies prioritised and addressed at RAC
      facility level culminated in an increase in the proportion of residents
      supplemented with vitamin D (p = 0.002) and development of falls prevention
      education. At organisation level a falls policy reflecting preventative evidence
      based guidelines and a new falls risk assessment procedure with aligned
      management plans were written, modified and implemented. A key disenabling
      mechanism identified by CoP members was limited time to engage in translation of
      evidence into practice whilst enabling mechanisms included proactive behaviours
      by staff and management. CONCLUSIONS: Interdisciplinary staff participating in a
      falls prevention CoP gained connectivity and knowledge and were able to
      facilitate the translation of falls prevention evidence into practice in the
      context of their RAC facility and RAC organisation. Support from RAC
      organisational and facility management to make the necessary investment in staff
      time to enable change in falls prevention practice is essential for success.

PMID- 29334964
TI  - Ginkgo biloba induced mood dysregulation: a case report.
AB  - BACKGROUND: Impairment of cognitive function as well as negative symptom is the
      major factor causing the decline of a patient's functioning in chronic stages of
      schizophrenia. However, until now, there were no definite treatment options that
      could effectively reduce the impairment. CASE PRESENTATION: We report a case of
      mood dysregulation associated with use of Ginkgo biloba in a patient with
      schizophrenia. After Ginkgo biloba was given, the patient experienced cluster
      symptoms of mood dysregulation including irritability, difficulty in controlling
      anger, agitation and restlessness. We estimated the possibility as "probable"
      according to Naranjo scale considering circumstantial evidence. CONCLUSIONS: This
      case suggests that Ginkgo biloba may have caused mood dysregulation in this
      patient. Although it is generally accepted as safe, more attention should be
      given to the adverse effect when treating with Ginkgo biloba.

PMID- 29334965
TI  - A novel IL-1RA-PEP fusion protein alleviates blood-brain barrier disruption after
      ischemia-reperfusion in male rats.
AB  - BACKGROUND: Current options to treat clinical relapse in inflammatory central
      nervous system (CNS) conditions such as cerebral ischemia-reperfusion injury are
      limited, and agents that are more effective are required. Disruption of the blood
      brain barrier is an early feature of lesion formation that correlates with
      clinical exacerbation and facilitates the entry of inflammatory medium and
      inflammatory cells. Interleukin-1 receptor antagonist (IL-1RA) is a naturally
      occurring anti-inflammatory antagonist of the interleukin-1 (IL-1) family. The
      broad-spectrum anti-inflammatory effects of IL-1RA have been investigated against
      various forms of neuroinflammation. However, the effect of IL-1RA on blood-brain
      barrier disruption following ischemia-reperfusion has not been reported. METHODS:
      In this study, we investigated the effects of IL-1RA and a novel protein (IL-1RA
      PEP) that was fused to IL-1RA with a cell penetrating peptide, on blood-brain
      barrier integrity, in male rats subjected to transient middle cerebral artery
      occlusion. RESULTS: After intravenous administration, IL-1RA-PEP (50 mg/kg)
      penetrated cerebral tissues more effectively than IL-1RA. Moreover, it preserved
      blood-brain barrier integrity, attenuated changes in expression and localization
      of tight junction proteins and matrix metalloproteinases, and enhanced
      angiogenesis in ischemic brain tissue. Further study suggested that the effects
      of IL-1RA-PEP on preserving blood-brain barrier integrity might be closely
      correlated with the p65/NF-kappaB pathway, as evidenced by the effects of the
      inhibitor JSH-23. CONCLUSIONS: Collectively, our results demonstrated that IL-1RA
      PEP could effectively penetrate the brain of rats with middle cerebral artery
      occlusion and ameliorate blood-brain barrier disruption. This finding might
      represent its novel therapeutic potential in the treatment of the cerebral
      ischemia-reperfusion injury.

PMID- 29334966
TI  - Atherogenic index of plasma is an effective index for estimating abdominal
      obesity.
AB  - BACKGROUND: The correlation between the atherogenic index of plasma (AIP) and
      waist circumference (WC) remains unknown. METHODS: A total of 5351 middle-aged
      men living in Southeastern China were surveyed using the random stratified
      cluster sampling method. A WC of 90 cm or greater was indicative of abdominal
      obesity, and AIP was calculated as follows: log [triglyceride (TG)/high-density
      lipoprotein-cholesterol (HDL-C)]. RESULTS: (1) A significantly higher AIP was
      observed in subjects with abdominal obesity than in those without abdominal
      obesity (P < 0.001). (2) Multivariate logistic regression analysis revealed an
      odds ratio of 1.93, 2.59 and 2.76 for abnormal AIP levels for the second, third
      and fourth WC quartiles, respectively (all P < 0.001) compared to the first WC
      quartile as a reference. (3) There was a linear correlation between WC and AIP,
      and a 1.0 cm increase in WC resulted in a 0.0175 rise in AIP. For AIP
      corresponding to moderate risk (0.12-0.21), WC was 85-90 cm; for AIP
      corresponding to high risk (> 0.21), WC was >90 cm. CONCLUSIONS: AIP of 0.12-0.21
      or >0.21 indicates a likelihood of borderline abdominal obesity or abdominal
      obesity, respectively, and the combination of WC and AIP may increase the
      specificity and sensitivity for detection of abdominal obesity in clinical
      practice. The results suggest that AIP may be used as a reference to estimate
      abdominal obesity.

PMID- 29334967
TI  - Risk factors and treatment of pneumothorax secondary to granulomatosis with
      polyangiitis: a clinical analysis of 25 cases.
AB  - OBJECTIVES: To investigate the risk factors and treatment strategies for
      pneumothorax secondary to granulomatosis with polyangiitis (GPA). METHOD:
      Retrospective analysis of cases with pneumothorax secondary to GPA from our own
      practice and published on literature. RESULTS: A total of 25 patients, 18 males
      and 7 females, mean age 44 +/- 15.7 years, were analyzed. Diagnosis included
      pneumothorax (11 cases), hydropneumothorax (n = 5), empyema (n = 8) and
      hemopneumothorax (n = 1). 88% (22/25) patients showed single/multiple pulmonary/
      subpleural nodules with/without cavitation on chest imaging. Erythrocyte
      sedimentation rate and C-reactive protein were both elevated. Corticosteroids and
      immunosuppressive agents were used in 16 cases. Five cases received steroid pulse
      therapy, of which 4 patients survived. Pleural drainage was effective in some
      patients. Seven patients underwent surgical operations. In the 10 fatal cases,
      infection and respiratory failure were the most common cause. Lung biopsy/
      autopsy showed lung/pleural necrotizing granulomatous vasculitis, breaking into
      the chest cavity, pleural fibrosis, bronchial pleural fistula, etc. The mean age
      in the death group was greater than the survival group (53 +/- 12.9 years vs 40.1
      +/- 14.7 years, p = 0.05), the ineffective pleural drainage was also higher in
      the death group (5/5 vs 0/7, p = 0.01). CONCLUSIONS: Pneumothorax was seen in the
      active GPA, due to a variety of reasons, and gave rise to high fatality rate.
      Aggressive treatment of GPA can improve the prognosis. Older and lack of response
      for pleural drainage indicates poor prognosis.

PMID- 29334969
TI  - The effects of workplace respect and violence on nurses' job satisfaction in
      Ghana: a cross-sectional survey.
AB  - BACKGROUND: Studies have established the negative effects of workplace disrespect
      and violence on the personal and professional well-being of nurses. In spite of
      this, only a few have directly investigated the effects of these issues on
      nurses' job satisfaction. In Africa, research on nurses' job satisfaction
      continues to focus largely on economic factors. The aim of this paper was,
      therefore, to investigate the impact of the non-economic factors of workplace
      violence and respect on the job satisfaction levels of nurses in Ghana. METHODS:
      The study employed a cross-sectional questionnaire survey. It involved 592
      qualified practising nurses working in public hospitals in Ghana. Data were
      collected between September 2013 and April 2014. RESULTS: The results showed
      that, overall, nurses were neither satisfied nor dissatisfied with their jobs (M
      = 3.19, SD = .54). More than half (52.7%) of the participants had been abused
      verbally, and 12% had been sexually harassed in the 12 months prior to the study.
      The majority of nurses, however, believed they were respected at the workplace (M
      = 3.77, SD = .70, Mode = 4). Multiple regression analyses showed that verbal
      abuse and perceived respect were statistically significant predictors of nurses'
      job satisfaction. Nurses who experienced verbal abuse and low level of respect
      were more likely to report low job satisfaction scores. CONCLUSION: It is
      concluded that non-financial strategies such as safe work environments which are
      devoid of workplace violence may enhance nurses' job satisfaction levels. A
      policy of "zero tolerance" for violence and low tolerance for disrespect could be
      put in place to protect nurses and healthcare professionals in general.

PMID- 29334968
TI  - Barriers and facilitators to cultural competence in rehabilitation services: a
      scoping review.
AB  - BACKGROUND: There is an important need to evaluate whether rehabilitation
      services effectively address the needs of minority culture populations with North
      America's increasingly diverse population. The objective of this paper was
      therefore to review and assess the state of knowledge of barriers and
      facilitators to cultural competence in rehabilitation services. METHOD: Our
      scoping review focused on cultural competence in rehabilitation services.
      Rehabilitation services included in this review were: audiology, speech-language
      pathology, physiotherapy, and occupational therapy. A search strategy was
      developed to identify relevant articles published from inception of databases
      until April 2015. Titles and abstracts were screened by two independent reviewers
      according to specific eligibility criteria with the use of a liberal-accelerated
      approach. Full-text articles meeting inclusion criteria were then screened. Key
      study characteristics were abstracted by the first reviewer, and findings were
      verified by the second reviewer. RESULTS: After duplicates were removed, 4303
      citations were screened. Included articles suggest that studies on cultural
      competence occur most frequently in occupational therapy (n = 17), followed by
      speech language pathology (n = 11), physiotherapy (n = 6), and finally audiology
      (n = 1). Primary barriers in rehabilitation services include language barriers,
      limited resources, and cultural barriers. Primary facilitators include cultural
      awareness amongst practitioners, cultural awareness in services, and explanations
      of health care systems. CONCLUSION: To our knowledge, this review is the first to
      summarize barriers and facilitators to cultural competence in rehabilitation
      fields. Insufficient studies were found to draw any conclusions with regards to
      audiological services. Minimal perspectives based on patient/caregiver
      experiences in all rehabilitation fields underscore a research gap. Future
      studies should aim to explore both patient/caregiver and practitioner
      perspectives as such data can help inform culturally competent practices.

PMID- 29334970
TI  - Digital Media-based Health Intervention on the promotion of Women's physical
      activity: a quasi-experimental study.
AB  - BACKGROUND: Technological advances have caused poor mobility and lower physical
      activity among humankind. This study was conducted to assess the impact of a
      digital media-based (multi-media, internet, and mobile phone) health intervention
      on promotion of women's physical activity. METHODS: In this quasi-experimental
      study, 360 women were divided into case and control groups. The digital media
      based educational intervention was conducted in two months in the case group
      electronically, using mail and Internet and telephone platforms. Physical
      activity was measured using International Physical Activity Questionnaire (IPAQ)
      that estimated women's physical activity rate in the previous week. Data was
      analyzed using descriptive and analytical statistics (ANOVA, chi-square, paired
      and independent t-tests) using SPSS 20. RESULTS: The mean score of knowledge,
      attitude and level of physical activity in the control group were not
      significantly different before and after the intervention. While in the case
      group, this difference before and after the intervention was significant (p <
      0.001), and mean scores of the above-mentioned factors increased after the
      intervention. CONCLUSIONS: Using innovative and digital media-based health
      education can be effective in improving health-based behavior such as physical
      activity. Therefore, it seems necessary to develop user-based strategies and
      strengthen the behavioral change theories and hypotheses based on digital media
      for effective influence on behavior. TRIAL REGISTRATION: Iranian Registry of
      Clinical Trials (IRCT), IRCT20160619028529N5 . Registered December 24, 2017
      [retrospectively registered].

PMID- 29334971
TI  - The titanium elastic nail serves as an alternative treatment for adult proximal
      radial shaft fractures: a cohort study.
AB  - BACKGROUND: To investigate whether closed reduction and internal fixation (CRIF)
      with titanium elastic nails (TENs) is a viable alternative treatment in proximal
      radial fractures. METHODS: In Kaohsiung Veterans General Hospital, from November
      2013 to April 2015, five adult male patients with forearm injuries (average age
      43 years; range 35-64 years) were treated for proximal radial shaft fractures.
      CRIF with TENs for radial shaft fractures was performed in these five patients.
      Radiographs; range of motions; visual analog scale (VAS); quick disabilities of
      the arm, shoulder, and hand (Quick DASH) questionnaire; and time to union were
      evaluated in our study. RESULTS: Mean follow-up period was 30 months (range 28-36
      months). Average time of radius union was 7.3 months (range 6-10 months).
      Functional outcomes 1 year after operation revealed an average Quick DASH score
      of 7.92 (range 4.5-25), an average VAS of 1.5 (range 1-3), and average forearm
      supination and pronation of 69.2 degrees  (range 45 degrees -75 degrees ) and
      82.5 degrees  (range 80 degrees -85 degrees ). No major complication was noted.
      CONCLUSIONS: CRIF with TEN for adult proximal radial fractures is a method to
      avoid extensive exposure or nerve injury during ORIF, especially in multiple
      trauma patients who require short operative time, uremia patients with
      ipsilateral forearm AV shunt, severe soft tissue swelling due to direct muscle
      contusion or strong muscularity before surgery, extensive radial fracture, and
      those in pursuit of cosmetic outcomes.

PMID- 29334972
TI  - Community readiness assessment for obesity research: pilot implementation of the
      Healthier Families programme.
AB  - BACKGROUND: This article reports on the development of a systematic approach to
      assess for community readiness prior to implementation of a behavioural
      intervention for childhood obesity. Using the Consolidated Framework for
      Implementation Research (CFIR), we developed research tools to evaluate local
      community centres' organisational readiness and their capacity to implement the
      intervention. METHODS: Four community Parks and Recreation centres from different
      states expressed interest in piloting an approach for dissemination and
      implementation of an evidence-based obesity prevention program for families with
      young children (Healthier Families). We conducted a mixed methods pre
      implementation evaluation using the CFIR to evaluate the alignment of
      organisational priorities with the Healthier Families programme. Written surveys
      assessed organisational readiness for change amongst organisational leaders,
      recreation programmers, and staff (N = 25). Key informant interviews were
      conducted among staff to assess organisational readiness and with community
      members to assess community readiness (N = 64). Surveys were analysed with
      univariate statistics. Interviews were transcribed, coded and analysed using
      inductive and deductive methods of analysis. RESULTS: Mixed-methods analysis led
      to the identification of three key domains on which to assess the organisational
      readiness to adopt a childhood obesity intervention, namely the physical
      infrastructure, the knowledge infrastructure, and the social infrastructure. The
      most critical measure of compatibility was the social infrastructure, since
      obstacles in the knowledge and physical infrastructures could be overcome by the
      strength of social resources, including the staff's ingenuity and commitment to a
      healthier community. This approach guided an assessment of organisational
      readiness prior to community organisations adopting and preparing to disseminate
      an obesity prevention community-based program in a wide-range of social and
      environmental contexts. CONCLUSIONS: Using a comprehensive pre-implementation
      assessment of the knowledge, physical and social infrastructures in a community
      is an essential step in effective dissemination for community-based behavioural
      interventions. Our research found that, when evaluating readiness and alignment,
      a responsive social infrastructure could provide the capacity to overcome
      potential barriers to implementation in either the knowledge or physical
      infrastructures.

PMID- 29334973
TI  - Options for reducing HIV transmission related to the dead space in needles and
      syringes.
AB  - BACKGROUND: When shared by people who inject drugs, needles and syringes with
      different dead space may affect the probability of HIV and hepatitis C virus
      (HCV) transmission differently. METHODS: We measured dead space in 56 needle and
      syringe combinations obtained from needle and syringe programs across 17
      countries in Europe and Asia. We also calculated the amounts of blood and HIV
      that would remain in different combinations following injection and rinsing.
      RESULTS: Syringe barrel capacities ranged from 0.5 to 20 mL. Needles ranged in
      length from 8 to 38 mm. The average dead space was 3 MUL in low dead space
      syringes with permanently attached needles, 13 MUL in high dead space syringes
      with low dead space needles, 45 MUL in low dead space syringes with high dead
      space needles, and 99 MUL in high dead space syringes with high dead space
      needles. Among low dead space designs, calculated volumes of blood and HIV viral
      burden were lowest for low dead space syringes with permanently attached needles
      and highest for low dead space syringes with high dead space needles. CONCLUSION:
      The dead space in different low dead space needle and syringe combinations varied
      substantially. To reduce HIV transmission related to syringe sharing, needle and
      syringe programs need to combine this knowledge with the needs of their clients.

PMID- 29334974
TI  - Prevalence of dysmenorrhea and predictors of its pain intensity among Palestinian
      female university students.
AB  - BACKGROUND: Few studies on gynaecological problems of young females in Arab
      countries were published. The aim of this study was to determine the prevalence
      of dysmenorrhea and predictors of its pain among university students in
      Palestine. METHODS: A cross - sectional study was carried out on a randomly
      selected sample of An-Najah National University female students. A pre-designed
      questionnaire, which included questions regarding menstrual cycle, pain during
      menstruation, life style, nutritional habits, and symptoms associated with
      menstrual pain, was used. Pain intensity was measured using visual analogue
      scale. RESULTS: A total of 956 female students were involved in the study. Of the
      total study sample, 846 (85.1%) reported having pain during menstruation; i.e.
      dysmenorrhea. Dysmenorrhea was significantly [(p = 0.027); OR = 1.5, 95% CI (1.05
      2.19)] associated with age at menarche. The mean score of pain among dysmenorrhic
      females was 6.79 +/- 2.64. The majority (654; 80.34%) of dysmenorrhic females
      reported having moderate/ severe pain. Univariate analysis using Chi-square test
      for factors associated with moderate/severe pain among dysmenorrhic females were
      irregular cycle [(p = 0.015); OR = 1.57, 95% CI = (1.09-2.30)], skipping
      breakfast [(p < 0.001); OR = 1.93, 95% CI = (1.33-2.79)], academic specialization
      [(p = 0.03; OR = 2.2, 95% CI = (1.21-3.98)] for medical specialization with
      reference to students in humanities), high stress level [(p = 0.036; OR = 1.53,
      95% CI = (1.03-2.28)], and living in dormitories [(p = 0.034); OR = 1.72, 95% CI
      = (1.04-2.86)]. Multivariate analysis using binary logistic regression enter
      method showed that medical specialization [(p = 0.045); OR = 1.92, 95% CI = (1.02
      3.64)] for medical students with reference to students in humanities), skipping
      breakfast [(p = 0.001); OR = 1.96, 95% CI = (1.35-2.86)], and irregular cycle [(p
      = 0.022); OR = 1.56, 95% CI = (1.07-2.29)] were the only significant predictors
      of moderate/severe dysmenorrhic pain. CONCLUSION: There is a high proportion of
      dysmenorrhea among Palestinian female university students. Skipping breakfast was
      the strongest predictor for moderate/severe dysmenorrhea. Increased awareness
      regarding factors that might influence the intensity of dysmenorrhic pain is
      needed.

PMID- 29334976
TI  - Plants traditionally used to make Cantonese slow-cooked soup in China.
AB  - BACKGROUND: Lao huo liang tang (Cantonese slow-cooked soup, CSCS) is popular in
      Guangdong, China, and is consumed by Cantonese people worldwide as a delicious
      appetizer. Because CSCS serves as an important part of family healthcare,
      medicinal plants and plant-derived products are major components of CSCS.
      However, a collated record of the diverse plant species and an ethnobotanical
      investigation of CSCS is lacking. Because of globalization along with a renewed
      interest in botanical and food therapy, CSCS has attracted a growing attention in
      soup by industries, scientists, and consumers. This study represents the first
      attempt to document the plant species used for CSCS in Guangdong, China, and the
      associated ethnomedical function of plants, including their local names, part(s)
      used, flavors, nature, preparation before cooking, habitats, and conservation
      status. METHODS: In 2014-2017, participatory approaches, open-ended
      conversations, and semi-structured interviews were conducted with 63 local people
      and 48 soup restaurant owners (111 interviews) to better understand the
      biocultural context of CSCS, emphasizing ethnobotanical uses of plants in
      Guangdong Province, China. Product samples and voucher specimens were collected
      for taxonomic identification. Mention Index (QI), frequency of use index (FUI),
      and economic index (EI) were adopted to evaluate the significance of each plant
      in the food supply. RESULTS: A total of 97 plant species belonging to 46 families
      and 90 genera were recorded as having been used in CSCS in the study area.
      Recorded menus consisted of one or several plant species, with each one used for
      different purposes. They were classified into 11 functions, with clearing heat
      being the most common medicinal function. Of the 97 species, 19 grew only in the
      wild, 8 species were both wild and cultivated, and 70 species were cultivated.
      Roots and fruits were the most commonly used plant parts in the preparation of
      CSCS. According to the national evaluation criteria, six of these species are
      listed on "China's red list" including two endangered, two critically endangered,
      one near-threatened, and one vulnerable species. The QI, FUI, and EI of the 97
      species in the study varied between 0.09 and 1, 0.23 and 9.95, and 0.45 and 6.58,
      respectively. CONCLUSIONS: As an important part of Cantonese culture, CSCS has
      been popularized as a local cuisine with a healthcare function. CSCS also
      reflects the plant species richness and cultural diversity of Guangdong Province.
      Future research on the safety and efficacy of CSCS as well as on ecological and
      cultural conservation efforts is needed for the sustainable growth of China's
      botanical and medicinal plant industry.

PMID- 29334975
TI  - Molecular characterization of duck enteritis virus UL41 protein.
AB  - BACKGROUND: Duck enteritis virus (DEV) belongs to the subfamily
      Alphaherpesvirinae, and information on the DEV UL41 gene is limited. METHODS: The
      DEV UL41 gene was cloned into the pET32a(+) vector and expressed in a prokaryotic
      expression system. Antiserum was raised against a bacterially expressed UL41-His
      fusion protein for further experiments. Transcription was quantified and UL41
      protein expression levels were determined in DEV-infected cells at different time
      points by RT-qPCR and western blotting, respectively. DEV virions were purified
      by sucrose gradient centrifugation and analyzed by mass spectrometry to identify
      protein content. We confirmed the DEV UL41 gene kinetic class using a
      pharmacological test. IFA was used to analyze the intracellular localization of
      pUL41. RESULTS: The recombinant expression plasmid, pET-32a(+)-UL41, which highly
      expresses a 76.0 kDa fusion protein, was constructed and expressed in E. coli
      BL21 (DE3) after induction with 0.2 mM IPTG at 30  degrees C for 10 h, generating
      a specific mouse anti-UL41 protein polyclonal antibody. RT-qPCR and western blot
      analyses revealed that the UL41 transcript number peaked at 36 hpi, and peak
      protein expression occurred at 48 hpi. The pharmacological test showed that UL41
      was a gamma2 gene. Mass spectrometry analysis showed that pUL41 was a virion
      component. IFA results revealed that pUL41 was localized throughout DEV-infected
      cells but only localized to the cytoplasm of transfected cells. DEV pUL47
      translocated pUL41 to the nuclei of DEF cells; this translocation was dependent
      on predicted pUL47 NLS signals (40-50 aa and 768-777 aa). CONCLUSIONS: DEV UL41
      is a gamma2 gene that encodes a virion structural protein, pUL41 localizes
      throughout DEV-infected cells but only localizes to the cytoplasm of transfected
      cells. pUL41 cannot autonomously localize to the nucleus, as this nuclear
      localization is dependent on predicted DEV pUL47 NLS signals (40-50 aa and 768
      777 aa).

PMID- 29334977
TI  - Ethnoecology of the interchange of wild and weedy plants and mushrooms in
      Phurepecha markets of Mexico: economic motives of biotic resources management.
AB  - BACKGROUND: Interactions between societies and nature are regulated by complex
      systems of beliefs, symbolism, customs, and worldviews (kosmos), ecological
      knowledge (corpus), and management strategies and practices (praxis), which are
      constructed as product of experiences and communication of people throughout
      time. These aspects influence social relations, life strategies, and cultural
      identity, and all of them in turn influence and are influenced by local and
      regional patterns of interchange. In this study, we analyze the interchange of
      wild and weedy plants and mushrooms in traditional markets of the Phurepecha
      region of Mexico. Particularly, the social relations constructed around the
      interchange of these products; how knowledge, cultural values, and ecological
      factors influence and are influenced by interchange; and how all these factors
      influence the type and intensity of biotic resources management. METHODS: We
      studied three main traditional markets of the Phurepecha region of Michoacan,
      Mexico, through 140 visits to markets and 60 semi-structured interviews to
      sellers of wild and weedy plants and mushrooms. In nearly 2 years, we carried out
      80 visits and 30 interviews in the "Barter Market", 20 visits and 15 interviews
      in the "Phurepecha Tianguis", and 40 visits and 15 interviews to the "Municipal
      Market". We documented information about the spaces of interchange that form the
      markets, the types of interchange occurring there, the cultural and economic
      values of the resources studied, the environmental units that are sources of such
      resources, the activities associated to resources harvesting and, particularly,
      the management techniques practiced to ensure or increase their availability. We
      analyzed the relations between the amounts of products interchanged, considered
      as pressures on the resources; the perception of their abundance or scarcity,
      considered as the magnitude of risk in relation to the pressures referred to; and
      the management types as response to pressures and risk. RESULTS: We recorded 38
      species of wild and weedy plants and 15 mushroom species interchanged in the
      markets. We characterized the spaces of interchange, the interchange types, and
      social relations among numerous Phurepecha communities which maintain the main
      features of pre-Columbian markets. The products analyzed are differentially
      valued according to their role in people's life, particularly food, medicine,
      rituals, and ornamental purposes. The highest cultural values were identified in
      multi-purpose plant and mushroom resources and, outstandingly, in ornamental and
      ritual plants. In markets, women are the main actors and connectors of the
      regional households' activities of use and management of local resources and
      ecosystems. The interrelationships between worldviews, knowledge, and practices
      are visible through the interchange of the products analyzed, including the types
      of environments comprised in communitarian territories, agricultural calendars,
      and feasts. Those plants and mushrooms are highly valued but relatively scarce
      according to the demand on them receiving special attention and management
      practices directed to ensure or increase their availability. With the exception
      of most mushrooms and ornamental and ritual plants, which have high economic and
      cultural values, there are those that are relatively scarce and under high risk,
      but are obtained through simple gathering from the wild. CONCLUSIONS: Traditional
      markets are crucial part of the subsistence strategy of Phurepecha people based
      on the multiple use of resources and ecosystems at the local and regional levels.
      The markets influence social relations, cultural identity, and preservation of
      traditional knowledge and biodiversity. In general, the demand of products in
      markets enhances innovation and practices for ensuring or increasing their
      availability, particularly those that are naturally scarce. However, it was
      notorious that, althoug mushrooms and ritual plants have high demand and value in
      markets, most of them are obtained by simple gathering.

PMID- 29334978
TI  - Plasma virome of cattle from forest region revealed diverse small circular ssDNA
      viral genomes.
AB  - BACKGROUND: Free-range cattle are common in the Northeast China area, which have
      close contact with farmers and may carry virus threatening to cattle and farmers.
      METHODS: Using viral metagenomics we analyzed the virome in plasma samples
      collected from 80 cattle from the forested region of Northeast China. RESULTS:
      The virome of cattle plasma is composed of the viruses belonging to the families
      including Parvoviridae, Papillomaviridae, Picobirnaviridae, and divergent viral
      genomes showing sequence similarity to circular Rep-encoding single stranded
      (CRESS) DNA viruses. Five such CRESS-DNA genomes were full characterized, with
      Rep sequences related to circovirus and gemycircularvirus. Three bovine
      parvoviruses belonging to two different genera were also characterized.
      CONCLUSION: The virome in plasma samples of cattle from the forested region of
      Northeast China was revealed, which further characterized the diversity of
      viruses in cattle plasma.

PMID- 29334979
TI  - Measuring spatial accessibility to healthcare services with constraint of
      administrative boundary: a case study of Yanqing District, Beijing, China.
AB  - BACKGROUND: The two-step floating catchment area (2SFCA) method, which is one of
      the most widely used methods for measuring healthcare spatial accessibility,
      defines the catchment area of each facility as the area within a certain distance
      from the facility. However, in some cases, the service utilization behavior is
      constrained by administrative boundaries, therefore the definition of catchment
      area within a certain distance may be inappropriate. METHODS: In this study, we
      aim to propose a modification of the 2SFCA method for measuring spatial
      accessibility to healthcare services in a system constrained by administrative
      boundaries. The proposed method defines the catchment areas of healthcare
      facilities within certain administrative units. The method is applied in a case
      study of the healthcare services in Yanqing District of Beijing, China. Three
      types of healthcare facilities, including general hospitals, community healthcare
      centers and stations, are included. RESULTS: Based on the sensitivity analysis of
      the distance-decay parameter beta, result of the beta = 1 scenario is relatively
      appropriate and is utilized for further analysis. The difference between spatial
      accessibility with or without constraint of administrative boundary is relatively
      significant. The results of the proposed model show that the village-level
      spatial accessibility to healthcare services shows a significant disparity, and
      the uneven distribution of general hospitals is the main cause. CONCLUSIONS: The
      constraint of administrative boundary has a significant impact on healthcare
      accessibility, which verifies the validity of the modification proposed by this
      study in empirical studies. The empirical results also lead to policy
      recommendations to improve healthcare equity in the study area. At the town
      level, the improvement of equity in healthcare accessibility could be achieved in
      two ways. First, the sizes of community healthcare centers in towns with small
      accessibility scores should be expanded. Second, new general hospitals can be
      built in the eastern part of Yanqing District. Within each town, to improve the
      equity in healthcare accessibility, community healthcare stations should be
      expanded or newly built in the periphery villages.

PMID- 29334980
TI  - Reoperation for a giant arch anastomotic pseudoaneurysm eleven years after total
      arch replacement with island reconstruction.
AB  - BACKGROUND: The long-term effects of some surgical treatment procedures of arch
      replacement for aortic dissection or aortic aneurysm are unknown. CASE
      PRESENTATION: The present study reports the case of a 68-year-old man admitted to
      our hospital for aortic arch anastomotic pseudoaneurysm with concomitant aortic
      root enlargement and coronary artery stenosis. Eleven years ago, at the age of 56
      years, he underwent total arch replacement with island reconstruction for chronic
      aortic dissection. We performed a second total arch replacement, aortic root
      replacement, and coronary artery bypass, using a cardiopulmonary bypass with
      cannulation through the right subclavian artery, femoral artery, and femoral vein
      prior to re-sternotomy. We also used selective cerebral perfusion.
      Postoperatively, the patient temporarily required reintubation; however, he was
      discharged in good condition on the fiftieth postoperative day. CONCLUSIONS: This
      case suggests that island reconstruction has the potential to cause arch
      anastomotic pseudoaneurysms, particularly after a long postoperative period.

PMID- 29334981
TI  - Production of highly and broad-range specific monoclonal antibodies against
      hemagglutinin of H5-subtype avian influenza viruses and their differentiation by
      mass spectrometry.
AB  - BACKGROUND: The highly pathogenic avian influenza viruses of the H5 subtype, such
      as the H5N1 viral strains or the novel H5N8 and H5N2 reassortants, are of both
      veterinary and public health concern worldwide. To combat these viruses,
      monoclonal antibodies (mAbs) against H5 hemagglutinin (HA) play a significant
      role. These mAbs are effective diagnostic and therapeutic agents and powerful
      tools in vaccine development and basic scientific research. The aim of this study
      was to obtain diagnostically valuable mAbs with broad strain specificity against
      H5-subtype AIVs. RESULTS: We applied the hybridoma method to produce anti-HA
      mAbs. The cloning and screening procedures resulted in the selection of 7 mouse
      hybridoma cell lines and their respective antibody clones. Preliminary
      immunoreactivity studies showed that these newly established mAbs, all of the
      IgG1 isotype, had high specificity and broad-range activities against the H5 HAs.
      However, these studies did not allow for a clear distinction among the selected
      antibodies and mAb-secreting hybridoma clones. To differentiate the analyzed mAbs
      and determine the exact number of hybridoma clones, peptide mapping of the Fc and
      Fab fragments was performed using a Matrix-Assisted Laser Desorption Ionization
      Time of Flight (MALDI-TOF/TOF) mass spectrometer. Detailed analyses of the
      acquired MS and MS/MS spectra confirmed that the Fc fragments constituted highly
      conserved species- and isotype-immunoglobulin components, whereas the Fab
      fragments exhibited considerable variation in the sequences that determine
      antibody specificity. This approach enabled unambiguous characterization of the
      selected mAbs according to their peptide composition. As a result, 6 different
      clones were distinguished. CONCLUSIONS: Our work provided a unique panel of anti
      H5 HA mAbs, which meets the demand for novel, high-specificity analytical tools
      for use in serologic surveillance. Applications of these mAbs in areas other than
      diagnostics are also possible. Moreover, we demonstrated for the first time that
      peptide mapping of antibody fragments with mass spectrometry is an efficient
      method for the differentiation of antibody clones and relevant antibody-producing
      cell lines. The method may be successfully used to characterize mAbs at the
      protein level.

PMID- 29334982
TI  - Genome-wide identification, characterization and classification of ionotropic
      glutamate receptor genes (iGluRs) in the malaria vector Anopheles sinensis
      (Diptera: Culicidae).
AB  - BACKGROUND: Ionotropic glutamate receptors (iGluRs) are conserved ligand-gated
      ion channel receptors, and ionotropic receptors (IRs) were revealed as a new
      family of iGluRs. Their subdivision was unsettled, and their characteristics are
      little known. Anopheles sinensis is a major malaria vector in eastern Asia, and
      its genome was recently well sequenced and annotated. METHODS: We identified
      iGluR genes in the An. sinensis genome, analyzed their characteristics including
      gene structure, genome distribution, domains and specific sites by bioinformatic
      methods, and deduced phylogenetic relationships of all iGluRs in An. sinensis,
      Anopheles gambiae and Drosophila melanogaster. Based on the characteristics and
      phylogenetics, we generated the classification of iGluRs, and comparatively
      analyzed the intron number and selective pressure of three iGluRs subdivisions,
      iGluR group, Antenna IR and Divergent IR subfamily. RESULTS: A total of 56 iGluR
      genes were identified and named in the whole-genome of An. sinensis. These genes
      were located on 18 scaffolds, and 31 of them (29 being IRs) are distributed into
      10 clusters that are suggested to form mainly from recent gene duplication. These
      iGluRs can be divided into four groups: NMDA, non-NMDA, Antenna IR and Divergent
      IR based on feature comparison and phylogenetic analysis. IR8a and IR25a were
      suggested to be monophyletic, named as Putative in the study, and moved from the
      Antenna subfamily in the IR family to the non-NMDA group as a sister of
      traditional non-NMDA. The generated iGluRs of genes (including NMDA and
      regenerated non-NMDA) are relatively conserved, and have a more complicated gene
      structure, smaller omega values and some specific functional sites. The iGluR
      genes in An. sinensis, An. gambiae and D. melanogaster have amino-terminal domain
      (ATD), ligand binding domain (LBD) and Lig_Chan domains, except for IR8a that
      only has the LBD and Lig_Chan domains. However, the new concept IR family of
      genes (including regenerated Antenna IR, and Divergent IR), especially for
      Divergent IR are more variable, have a simpler gene structure (intron loss
      phenomenon) and larger omega values, and lack specific functional sites. These IR
      genes have no other domains except for Antenna IRs that only have the Lig_Chan
      domain. CONCLUSIONS: This study provides a comprehensive information framework
      for iGluR genes in An. sinensis, and generated the classification of iGluRs by
      feature and bioinformatics analyses. The work lays the foundation for further
      functional study of these genes.

PMID- 29334983
TI  - An individually tailored family-centered intervention for pediatric obesity in
      primary care: study protocol of a randomized type II hybrid effectiveness
      implementation trial (Raising Healthy Children study).
AB  - BACKGROUND: Pediatric obesity is a multi-faceted public health concern that can
      lead to cardiovascular diseases, cancers, and early mortality. Small changes in
      diet, physical activity, or BMI can significantly reduce the possibility of
      developing cardiometabolic risk factors. Family-based behavioral interventions
      are an underutilized, evidence-based approach that have been found to
      significantly prevent excess weight gain and obesity in children and adolescents.
      Poor program availability, low participation rates, and non-adherence are noted
      barriers to positive outcomes. Effective interventions for pediatric obesity in
      primary care are hampered by low family functioning, motivation, and adherence to
      recommendations. METHODS: This (type II) hybrid effectiveness-implementation
      randomized trial tests the Family Check-Up 4 Health (FCU4Health) program, which
      was designed to target health behavior change in children by improving family
      management practices and parenting skills, with the goal of preventing obesity
      and excess weight gain. The FCU4Health is assessment driven to tailor services
      and increase parent motivation. A sample of 350 families with children aged 6 to
      12 years who are identified as overweight or obese (BMI >= 85th percentile for
      age and gender) will be enrolled at three primary care clinics [two Federally
      Qualified Healthcare Centers (FQHCs) and a children's hospital]. All clinics
      serve predominantly Medicaid patients and a large ethnic minority population,
      including Latinos, African Americans, and American Indians who face disparities
      in obesity, cardiometabolic risk, and access to care. The FCU4Health will be
      coordinated with usual care, using two different delivery strategies: an embedded
      approach for the two FQHCs and a referral model for the hospital-based clinic. To
      assess program effectiveness (BMI, body composition, child health behaviors,
      parenting, and utilization of support services) and implementation outcomes (such
      outcomes as acceptability, adoption, feasibility, appropriateness, fidelity, and
      cost), we use a multi-method and multi-informant assessment strategy including
      electronic health record data, behavioral observation, questionnaires,
      interviews, and cost capture methods. DISCUSSION: This study has the potential to
      prevent excess weight gain, obesity, and health disparities in children by
      establishing the effectiveness of the FCU4Health and collecting information
      critical for healthcare decision makers to support sustainable implementation of
      family-based programs in primary care. TRIAL REGISTRATION: NCT03013309
      ClinicalTrials.gov.

PMID- 29334984
TI  - New insights into ANGPLT3 in controlling lipoprotein metabolism and risk of
      cardiovascular diseases.
AB  - Dyslipidemia, characterized by elevation of plasma low density lipoprotein
      cholesterol (LDL-C), triglyceride (TG) and reduction of plasma high density
      lipoprotein cholesterol (HDL-C), has been verified as a causal risk factor for
      cardiovascular diseases (CVD), leading to a high mortality rate in general
      population. It is important to understand the molecular metabolism underlying
      dyslipidemia in order to reduce the risk and to develop effective therapeutic
      approaches against CVD. ANGPTL3 (human) or Angptl3 (mouse), one member of the
      angiopoietin-like protein (ANGPTL) family, has been identified as an important
      regulator of lipid metabolism by inhibiting LPL and EL activity. Results have
      demonstrated that inactivation of Angptl3 in mice could obviously reduce the
      level of TG, LDL-C and the atherosclerotic lesion size, leading to a lower risk
      for dyslipidemia and CVD. Additionally, in humans, carriers with homozygous LOF
      mutations in ANGPTL3 have lower plasma LDL-C, TG levels and lower risk of
      atherosclerosis compared to the non-carriers. Here, we collect the latest data
      and results, giving a new insight into the important role of ANGPTL3 in
      controlling lipoprotein metabolism. Finally, we introduce two update reports on
      the antisense oligonucleotide and monoclonal antibody-based inactivation of
      ANGPTL3 in human clinical trials, to identify that ANGPTL3 could be a novel and
      effective target for the treatment of dyslipidemia and CVD.

PMID- 29334985
TI  - Role of sleep duration and sleep-related problems in the metabolic syndrome among
      children and adolescents.
AB  - BACKGROUND: There is increasing recognition that sleep is a risk factor for
      metabolic syndrome (MetS). The aim of the present study was to analyze the
      relationship between self-reported sleep duration, sleep-related problems and the
      presence of MetS in children and adolescents from Bogota, D.C., Colombia.
      METHODS: This is a cross-sectional analysis from the FUPRECOL study (2014-15).
      Participants included 2779 (54.2% girls) youth from Bogota (Colombia). MetS was
      defined as the presence of >=3 of the metabolic abnormalities (hyperglycemia,
      hypertriglyceridemia, low high-density lipoprotein cholesterol [HDL-c],
      hypertension, and increased waist circumference) according to the criteria of de
      Ferranti/Magge and colleges. Self-reported sleep duration and sleep-related
      problems were assessed with the BEARS questionnaire. RESULTS: Logistic regression
      analysis showed that boys who meet recommended duration of sleep had a decreased
      risk of elevated blood glucose levels (Odds Ratio [OR] = 0.71, 95%CI [0.40-0.94];
      p = 0.031) compared to boys who have short-long sleep duration. Also, compared to
      young without sleep problems, excessive sleepiness during the day was related to
      low HDL-c levels in boys (OR = 1.36, 95%CI [1.02-1.83]; p = 0.036) and high
      triglyceride levels in girls (OR = 1.28, 95%CI [1.01-1.63]; p = 0.045). Girls
      with irregular sleep patterns had decreased HDL-c levels (OR = 0.71, 95%CI [0.55
      0.91]; p = 0.009). CONCLUSIONS: Recommended sleep duration was associated with a
      decreased risk of elevated fasting glucose levels in boys, and sleep problems was
      related to lower HDL-c in girls and higher triglyceride levels in boys. These
      findings suggested the clinical importance of improving sleep hygiene to reduce
      metabolic risk factors in children and adolescents.

PMID- 29334987
TI  - Representative survey on idiopathic environmental intolerance attributed to
      electromagnetic fields in Taiwan and comparison with the international
      literature.
AB  - BACKGROUND: Electromagnetic hypersensitivity refers to health effects attributed
      to electromagnetic fields (EMF) exposure and has been formally named "idiopathic
      environmental intolerance attributed to electromagnetic fields" (IEI-EMF) by the
      World Health Organization. Because of the growing use of cell phones, IEI-EMF has
      become a global public health concern. A survey in 2007 in Taiwan showed that the
      prevalence rate of IEI-EMF was 13.3%, which is higher than rates in studies
      conducted previously. The survey also found that the rate was higher in women.
      METHODS: To evaluate whether the prevalence rate of IEI-EMF is increasing and to
      verify the higher risk in women, we conducted a nationwide questionnaire survey
      using the same methods as the 2007 survey to assess the change in the prevalence
      rate of IEI-EMF in Taiwan. We also conducted a review of the literature and a
      meta-analysis to evaluate the changes in the prevalence rate around the world.
      RESULTS: On the basis of the representative sample of 3303 participants, we found
      that the prevalence rate of IEI-EMF in Taiwan declined from 13.3% to 4.6% over a
      period of 5 years. The literature review also found the prevalence rates in other
      countries to be decreasing, instead of increasing as predicted previously. The
      meta-analysis of the data from the literature showed that women are more likely
      to have IEI-EMF than men, with an odds ratio of 1.19 (95% confidence interval:
      1.01-1.40). CONCLUSIONS: We found the prevalence rate of IEI-EMF has been
      declining, instead of increasing as predicted previously. Women are more likely
      to report having IEI-EMF than men. Further studies to explore the causes leading
      to the declines may help the public, scientific community, and government deal
      with idiopathic intolerance to other environmental exposures.

PMID- 29334986
TI  - Bridging pro-inflammatory signals, synaptic transmission and protection in spinal
      explants in vitro.
AB  - Multiple sclerosis is characterized by tissue atrophy involving the brain and the
      spinal cord, where reactive inflammation contributes to the neurodegenerative
      processes. Recently, the presence of synapse alterations induced by the
      inflammatory responses was suggested by experimental and clinical observations,
      in experimental autoimmune encephalomyelitis mouse model and in patients,
      respectively. Further knowledge on the interplay between pro-inflammatory agents,
      neuroglia and synaptic dysfunction is crucial to the design of unconventional
      protective molecules. Here we report the effects, on spinal cord circuits, of a
      cytokine cocktail that partly mimics the signature of T lymphocytes sub
      population Th1. In embryonic mouse spinal organ-cultures, containing neuronal
      cells and neuroglia, cytokines induced inflammatory responses accompanied by a
      significant increase in spontaneous synaptic activity. We suggest that cytokines
      specifically altered signal integration in spinal networks by speeding the decay
      of GABAA responses. This hypothesis is supported by the finding that synapse
      protection by a non-peptidic NGF mimetic molecule prevented both the changes in
      the time course of GABA events and in network activity that were left unchanged
      by the cytokine production from astrocytes and microglia present in the cultured
      tissue. In conclusion, we developed an important tool for the study of synaptic
      alterations induced by inflammation, that takes into account the role of neuronal
      and not neuronal resident cells.

PMID- 29334988
TI  - Epidermal Wnt signalling regulates transcriptome heterogeneity and proliferative
      fate in neighbouring cells.
AB  - BACKGROUND: Canonical Wnt/beta-catenin signalling regulates self-renewal and
      lineage selection within the mammalian epidermis. Although the transcriptional
      response of keratinocytes that receive a Wnt signal is well characterized, little
      is known about the mechanism by which keratinocytes in proximity to the Wnt
      receiving cell are co-opted to undergo a change in cell fate. RESULTS: To address
      this, we perform single-cell RNA-sequencing on mouse keratinocytes co-cultured
      with and without beta-catenin-activated neighbouring cells. We identify five
      distinct cell states in cultures that had not been exposed to the beta-catenin
      stimulus and show that the stimulus redistributes wild-type subpopulation
      proportions. Using temporal single-cell analysis, we reconstruct the cell fate
      change induced by Wnt activation from neighbouring cells. Gene expression
      heterogeneity is reduced in neighbouring cells and this effect is most dramatic
      for protein synthesis-associated genes. Changes in gene expression are
      accompanied by a shift to a more proliferative stem cell state. By integrating
      imaging and reconstructed sequential gene expression changes during the state
      transition we identify transcription factors, including Smad4 and Bcl3, that are
      responsible for effecting the transition in a contact-dependent manner.
      CONCLUSIONS: Our data indicate that non-cell autonomous Wnt/beta-catenin
      signalling decreases transcriptional heterogeneity. This furthers our
      understanding of how epidermal Wnt signalling orchestrates regeneration and self
      renewal.

PMID- 29334989
TI  - Implantation of a 3D-printed titanium sternum in a patient with a sternal tumor.
AB  - BACKGROUND: Primary malignant or metastatic sternal tumors are uncommon. A
      subtotal or total sternectomy can offer a radical form of treatment. The issue is
      to restore the structural integrity of the chest wall. CASE PRESENTATION: We
      report the implantation of an individualized 3D-printed titanium sternum in a
      patient with a sternal tumor. CONCLUSIONS: We believe that tridimensional print
      technologies may also change the strategy of chest wall reconstruction.

PMID- 29334990
TI  - Performance evaluation of existing immunoassays for Clonorchis sinensis infection
      in China.
AB  - BACKGROUND: Clonorchiasis ranks among the most important food-borne parasitic
      diseases in China. However, due to low compliance to traditional fecal
      examination techniques in the general population and medical personnel,
      immunodiagnosis is expected. This study evaluated, in parallel, the performance
      of four immunodiagnostic kits detecting clonorchiasis in China. RESULTS: A bank
      with 475 sera was established in this study. Except for the low performance of
      the kit detecting IgM, the other three kits detecting IgG showed sensitivities
      ranging from 81.51% (194/238) to 99.16% (236/238). Higher sensitivity was
      presented in heavy infection intensity [89.47% (68/76) to 100% (76/76)]. Among
      the four kits, the overall specificity varied from 73.42% (174/237) to 87.34%
      (207/237). It was observed that the specificity was lower in the sera of the
      participants living in clonorchiasis-endemic areas but without any parasite
      infection [67.5% (81/120) to 90% (108/120)], as compared to those from the non
      endemic area [94% (47/50) to 98% (49/50)]. The cross-reaction rate varied from
      14.93% (10/67) to 31.34% (21/67). Youden's index was -0.022, 0.689, 0.726, and
      0.802 for kits T1, T2, T3 and T4, respectively. Repeatability was high in all
      four kits. CONCLUSIONS: Three immunodiagnosis kits targeting IgG antibody had
      high performance on detecting chronic Clonorchis sinensis infection, but that
      detecting IgM antibody had not. The kits detecting IgG antibody also showed high
      sensitivity in heavy infection intensity. Research on immunological diagnosis of
      clonorchiasis is expected to be strengthened to improve the sensitivity in light
      infection and specificity.

PMID- 29334992
TI  - The efficacy of a multimodal physical activity intervention with supervised
      exercises, health coaching and an activity monitor on physical activity levels of
      patients with chronic, nonspecific low back pain (Physical Activity for Back Pain
      (PAyBACK) trial): study protocol for a randomised controlled trial.
AB  - BACKGROUND: Physical activity plays an important role in the management of
      chronic low back pain (LBP). Engaging in an active lifestyle is associated with a
      better prognosis. Nevertheless, there is evidence to suggest that patients with
      chronic LBP are less likely to meet recommended physical activity levels.
      Furthermore, while exercise therapy has been endorsed by recent clinical practice
      guidelines, evidence from systematic reviews suggests that its effect on pain and
      disability are at best moderate and not sustained over time. A limitation of
      current exercises programmes for chronic LBP is that these programmes are not
      designed to change patients' behaviour toward an active lifestyle. Therefore, we
      will investigate the short- and long-term efficacy of a multimodal intervention,
      consisting of supervised exercises, health coaching and use of an activity
      monitor (i.e. Fitbit Flex) compared to supervised exercises plus sham coaching
      and a sham activity monitor on physical activity levels, pain intensity and
      disability, in patients with chronic, nonspecific LBP. METHODS: This study will
      be a two-group, single-blind, randomised controlled trial. One hundred and sixty
      adults with chronic, nonspecific LBP will be recruited. Participants allocated to
      both groups will receive a group exercise programme. In addition, the
      intervention group will receive health coaching sessions (i.e. assisting the
      participants to achieve their physical activity goals) and an activity monitor
      (i.e. Fitbit Flex). The participants allocated to the control group will receive
      sham health coaching (i.e. encouraged to talk about their LBP or other problems,
      but without any therapeutic advice from the physiotherapist) and a sham activity
      monitor. Outcome measures will be assessed at baseline and at 3, 6 and 12 months
      post randomisation. The primary outcomes will be physical activity, measured
      objectively with an accelerometer, as well as pain intensity and disability at 3
      months post randomisation. Secondary outcomes will be physical activity, pain
      intensity and disability at 6 and 12 months post randomisation as well as other
      self-report measures of physical activity and sedentary behaviour, depression,
      quality of life, pain self-efficacy and weight-related outcomes at 3, 6, and 12
      months post randomisation. DISCUSSION: This study is significant as it will be
      the first study to investigate whether a multimodal intervention designed to
      increase physical activity levels reduces pain and disability, and increases
      physical activity levels compared to a control intervention in patients with
      chronic LBP. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03200509 . Registered
      on 28 June 2017.

PMID- 29334991
TI  - Role of the nervous system in cancer metastasis.
AB  - Cancer remains as one of the leading cause of death worldwide. The development of
      cancer involves an intricate process, wherein many identified and unidentified
      factors play a role. Although most studies have focused on the genetic
      abnormalities which initiate and promote cancer, there is overwhelming evidence
      that tumors interact within their environment by direct cell-to-cell contact and
      with signaling molecules, suggesting that cancer cells can influence their
      microenvironment and bidirectionally communicate with other systems. However,
      only in recent years the role of the nervous system has been recognized as a
      major contributor to cancer development and metastasis. The nervous system
      governs functional activities of many organs, and, as tumors are not independent
      organs within an organism, this system is integrally involved in tumor growth and
      progression.

PMID- 29334993
TI  - Quality of life in mucopolysaccharidoses: construction of a specific measure
      using the focus group technique.
AB  - OBJECTIVE: To describe the perceptions of patients, their caregivers, and their
      healthcare providers to the development of a new specific instrument for
      assessment of the quality of life (QoL) in patients with mucopolysaccharidoses
      (MPS) using a qualitative focus group (FG) design. FGs were held in two Brazilian
      states (Rio Grande do Sul and Rio de Janeiro). RESULTS: Three versions of the new
      instrument were developed, each for a different age group: children (age 8-12
      years), adolescents (age 13-17), and adults (age >= 18). The FGs mostly confirmed
      the relevance of items. All FGs unanimously agreed on the facets: School,
      Happiness, Life Prospects, Religiosity, Pain, Continuity of Treatment, Trust in
      Treatment, Relationship with Family, Relationship with Healthcare Providers,
      Acceptance, and Meaning of Life. The overall concept of QoL (as proposed by the
      WHO-World Health Organization) and its facets apply to this patient population.
      However, other specific facets-particularly concerning clinical manifestations
      and the reality of the disease-were suggested, confirming the need for the
      development of a specific QoL instrument for MPS.

PMID- 29334994
TI  - The relationship between home- and individual-level diet quality among African
      American and Hispanic/Latino households with young children.
AB  - BACKGROUND: The quality of most Americans' diets is far from optimal. Given that
      many Americans consume a significant portion of calories in the home, intervening
      in this setting could be beneficial. However, the relationship between the home
      food environment and diet quality is not well understood. This study examined the
      relationship between diet quality at the individual level with home-level diet
      quality using an index that measures compliance with federal dietary guidance.
      METHODS: This was a cross sectional study that enrolled 97 African American and
      Hispanic/Latino low-income parent-child dyads. Diet quality at the individual
      level was assessed through two 24-h dietary recalls collected for parents and
      children, respectively. Diet quality at the home level was assessed with two home
      food inventories conducted in participants' homes. Diet quality scores at the
      home and individual levels were computed by applying the Healthy Eating Index
      2010 (HEI-2010) to these data. Linear models adjusted for potential confounding
      factors were used to examine the relationship between diet quality at the home
      and individual levels. RESULTS: Total HEI-2010 scores from parents and children's
      diets were positively associated with HEI-2010 scores based on home food
      inventories (parent diet: beta: 0.36, 95% CI: 012-0.60; child diet: 0.38 95% CI:
      013-0.62). Positive associations were also observed between individual level and
      home level subcomponent HEI-2010 scores for total fruit (parent: 0.55 95% CI:
      0.16-0.94; child: 0.49 95% CI: 0.03-0.94), whole fruit (parent only: 0.41 95% CI:
      0.07-0.74), greens and beans (parent only: 0.39 95% CI: 0.05-0.74), and whole
      grain (children only: 0.33 95% CI: 0.04-0.63). CONCLUSION: This study
      demonstrated that individual level diet quality was positively associated with
      home-level diet quality. Findings from this study can help us to address
      modifiable targets of intervention in the home to improve diet quality.

PMID- 29334995
TI  - Antisense suppression of the nonsense mediated decay factor Upf3b as a potential
      treatment for diseases caused by nonsense mutations.
AB  - BACKGROUND: About 11% of all human genetic diseases are caused by nonsense
      mutations that generate premature translation termination codons (PTCs) in
      messenger RNAs (mRNA). PTCs not only lead to the production of truncated
      proteins, but also often result in  decreased mRNA abundance due to  nonsense
      mediated mRNA decay (NMD). Although pharmacological inhibition of NMD could be an
      attractive therapeutic approach for the treatment of diseases caused by nonsense
      mutations, NMD also regulates the expression of 10-20% of the normal
      transcriptome. RESULTS: Here, we investigate whether NMD can be inhibited to
      stabilize mutant mRNAs, which may subsequently produce functional proteins,
      without having a major impact on the normal transcriptome. We develop antisense
      oligonucleotides (ASOs) to systematically deplete each component in the NMD
      pathway. We find that ASO-mediated depletion of each NMD factor elicits different
      magnitudes of NMD inhibition in vitro and are differentially tolerated in normal
      mice. Among all of the NMD factors, Upf3b depletion is well tolerated, consistent
      with previous reports that UPF3B is not essential for development and regulates
      only a subset of the endogenous NMD substrates. While minimally impacting the
      normal transcriptome, Upf3b-ASO treatment significantly stabilizes the PTC
      containing dystrophin mRNA in mdx mice and coagulation factor IX mRNA in a
      hemophilia mouse model. Furthermore, when combined with reagents promoting
      translational read-through, Upf3b-ASO treatment leads to the production of
      functional factor IX protein in hemophilia mice. CONCLUSIONS: These data
      demonstrate that ASO-mediated reduction of the NMD factor Upf3b could be an
      effective and safe approach for the treatment of diseases caused by nonsense
      mutations.

PMID- 29334997
TI  - Effects of three frequencies of self-monitored blood glucose on HbA1c and quality
      of life in patients with type 2 diabetes with once daily insulin and stable
      control: a randomized trial.
AB  - OBJECTIVE: The optimal frequency of self-monitoring of blood glucose (SMBG) in
      patients with type 2 diabetes (T2DM) with stable glycemic control is unknown.
      This study investigated effects of 3 frequencies of SMBG on glycemic control and
      quality of life after 9 months in patients using one long-acting insulin
      injection a day. In an open-label, multi-center, primary-care, parallel (1:1:1)
      randomized trial in the Netherlands including patients with T2DM, HbA1c <= 58
      mmol/mol (<= 7.5%), stable glycemic control, treated with one insulin injection
      daily, three frequencies of 4-point glucose measurements (before meals and
      bedtime) were weekly (n = 22), every 2 weeks (n = 16) and monthly (n = 20) were
      compared. RESULTS: A total of 58 patients with T2DM were included by 38 general
      practitioners, which was lower then anticipated. There were no significant
      between group differences in HbA1c (mmol/mol); group C compared to A and B; - 2.7
      (95% CI - 6.4, 1.0) and - 1.0 (95% CI - 4.9, 3.0) and quality of life. Baring in
      mind the lower than anticipated inclusion rate, there were no significant
      differences in HbA1c and quality of life between three different frequencies of
      SMBG in patients with stable glycemic control using one long-acting insulin
      injection. Trial registration NCT01460459, registered 10-2011, recruitment
      between 05-2011 and 12-2011.

PMID- 29334998
TI  - Examining human paragonimiasis as a differential diagnosis to tuberculosis in The
      Gambia.
AB  - OBJECTIVE: Paragonimiasis is a foodborne trematode infection of the lungs caused
      by Paragonimus spp., presenting clinically with similar symptoms to active
      tuberculosis (TB). Worldwide, an estimated 20.7 million people are infected with
      paragonimiasis, but relatively little epidemiological data exists for Africa.
      Given a recently reported case, we sought to establish whether paragonimiasis
      should be considered as an important differential diagnosis for human TB in The
      Gambia, West Africa. RESULTS: We developed a novel PCR-based diagnostic test for
      Paragonimus species known to be found in West Africa, which we used to examine
      archived TB negative sputum samples from a cross-sectional study of volunteers
      with tuberculosis-like symptoms from communities in the Western coastal region of
      The Gambia. Based on a "zero patient" design for detection of rare diseases, 300
      anonymised AFB smear negative sputum samples, randomly selected from 25 villages,
      were screened for active paragonimiasis by molecular detection of Paragonimus
      spp. DNA. No parasite DNA was found in any of the sputa of our patient group.
      Despite the recent case report, we found no evidence of active paragonimiasis
      infection masking as TB in the Western region of The Gambia.

PMID- 29334996
TI  - Italian guidelines on the assessment and management of pediatric head injury in
      the emergency department.
AB  - OBJECTIVE: We aim to formulate evidence-based recommendations to assist
      physicians decision-making in the assessment and management of children younger
      than 16 years presenting to the emergency department (ED) following a blunt head
      trauma with no suspicion of non-accidental injury. METHODS: These guidelines were
      commissioned by the Italian Society of Pediatric Emergency Medicine and include a
      systematic review and analysis of the literature published since 2005. Physicians
      with expertise and experience in the fields of pediatrics, pediatric emergency
      medicine, pediatric intensive care, neurosurgery and neuroradiology, as well as
      an experienced pediatric nurse and a parent representative were the components of
      the guidelines working group. Areas of direct interest included 1) initial
      assessment and stabilization in the ED, 2) diagnosis of clinically important
      traumatic brain injury in the ED, 3) management and disposition in the ED. The
      guidelines do not provide specific guidance on the identification and management
      of possible associated cervical spine injuries. Other exclusions are noted in the
      full text. CONCLUSIONS: Recommendations to guide physicians practice when
      assessing children presenting to the ED following blunt head trauma are reported
      in both summary and extensive format in the guideline document.

PMID- 29334999
TI  - The plant alkaloid tetrandrine inhibits metastasis via autophagy-dependent
      Wnt/beta-catenin and metastatic tumor antigen 1 signaling in human liver cancer
      cells.
AB  - BACKGROUND: Tetrandrine is a bisbenzylisoquinoline alkaloid isolated from the
      Chinese medicinal herb Stephania tetrandra S. Moore. We previously demonstrated
      that tetrandrine exhibits potent antitumor effects in many types of cancer cells.
      In this study, we investigated the effects of tetrandrine on human hepatocellular
      carcinoma (HCC) metastasis. METHODS: The invasion and migration effects were
      evaluated via wound healing and transwell assays. Immunofluorescence and western
      blotting analyses were used to investigate the levels of epithelial-mesenchymal
      transition (EMT)-related protein. A metastasis model was established to
      investigate the inhibitory effect of tetrandrine on hepatocellular carcinoma
      metastasis in vivo. RESULTS: Tetrandrine inhibits HCC invasion and migration by
      preventing cell EMT. The underlying mechanism was closely associated with
      tetrandrine-induced human liver cell autophagy, which inhibits Wnt/beta-catenin
      pathway activity and decreases metastatic tumor antigen 1 (MTA1) expression to
      modulate cancer cell metastasis. CONCLUSION: Our findings demonstrate, for the
      first time, that tetrandrine plays a significant role in the inhibition of human
      hepatocellular carcinoma metastasis and provide novel insights into the
      application of tetrandrine in clinical HCC treatment.

PMID- 29335001
TI  - Different clinical presentation and management of temporal bone fibrous dysplasia
      in children.
AB  - BACKGROUND: Fibrous dysplasia is a slowly progressive benign fibro-osseous
      disorder that involves one or multiple bones with a unilateral distribution in
      most cases. It is a lesion of unknown etiology, uncertain pathogenesis, and
      diverse histopathology. Temporal bone involvement is the least frequently
      reported type, especially in children. We reviewed available articles regarding
      fibrous dysplasia with temporal bone involvement in children and added four
      patients aged 7 to 17 years who were diagnosed and treated in our institution
      from 2006 to 2017. The patients' clinical picture comprised head deformity,
      external canal stenosis, headache, progressive conductive and/or sensorineural
      hearing loss, tinnitus, and sudden deafness. Two patients had experienced severe
      episodic vertigo with nausea and vomiting. Two were referred to us with external
      canal obstruction and secondary cholesteatoma formation with broad middle ear
      destruction. One was diagnosed with acute mastoiditis and intracranial
      complications. Optimal management of fibrous dysplasia is unclear and can be
      challenging, especially in children. In our two patients with disease expansion
      and involvement of important structures, surgical treatment was abandoned and a
      "wait-and-scan" policy was applied. The other two were qualified for surgical
      treatment. One patient underwent two surgeries: modified lateral petrosectomy
      (canal left open) with pathological tissue removal, cavity obliteration, and
      subsequent tympanoplasty. Another patient with extensive destruction of the left
      temporal bone underwent canal wall down mastoidectomy with perisinus abscess
      drainage and revision 12 months later. Tympanoplasty was unsatisfactory in both
      patients because of slow progression of the middle ear pathology. None of our
      patients underwent pharmacological treatment. CONCLUSIONS: In younger patients,
      observation and a "wait-and-scan" protocol is relevant until significant
      function, or cosmetic deficits are obvious. Surgery is not preferred and should
      be delayed until puberty because fibrous dysplasia has a tendency to stabilize
      after adolescence. In patients with severe symptoms medical treatment can be
      implemented, but safety of this treatment in children remain controversial.

PMID- 29335000
TI  - Molecular characterization of Babesia microti thioredoxin (BmTrx2) and its
      expression patterns induced by antiprotozoal drugs.
AB  - BACKGROUND: Human babesiosis is an infectious disease that is epidemic in various
      regions all over the world. The predominant causative pathogen of this disease is
      the intra-erythrocytic parasite Babesia microti. The thioredoxin system is one of
      the major weapons that is used in the resistance to the reactive oxygen species
      (ROS) and reactive nitrogen species (RNS) produced by host immune system. In
      other intra-erythrocytic apicomplexans like the malaria parasite Plasmodium
      falciparum, anti-oxidative proteins are promising targets for the development of
      anti-parasitic drugs. However, to date, the sequences and biological properties
      of thioredoxins and thioredoxin-like molecules of B. microti remain unknown.
      Understanding the molecular characterization and function of B. microti
      thioredoxins may help to develop anti-Babesia drugs and controlling babesiosis.
      METHODS: The full-length B. microti thioredoxin 2 (BmTrx2) gene was obtained
      using a rapid amplification of cDNA ends (RACE) method, and the deduced BmTrx2
      amino acid sequence was analyzed using regular bioinformatics tools. Recombinant
      BmTrx2 protein was expressed in vitro and purified using His-tag protein affinity
      chromatography resins. Reverse transcription PCR, quantitative real-time PCR and
      Western blot were employed to detect the expression and native proteins of
      BmTrx2. Indirect immunofluorescence assay was used to localize BmTrx2 in B.
      microti. Bovine insulin reduction assays were used to determine the enzyme
      activity of the purified recombinant BmTrx2 protein. RESULTS: The full-length
      BmTrx2 was 564 bp with a 408 bp open reading frame encoding a protein of 135
      amino acids. The predicted molecular weight of the protein was 15.5 kDa. A
      conserved thioredoxin-like family domain was found in BmTrx2. The expression of
      BmTrx2 was upregulated on both the third and eighth day post-infection in mice,
      whereas expression was downregulated during the beginning and later stages. The
      results of Western blot analysis showed the native BmTrx2 in parasite lysates
      could be detected by mouse anti-BmTrx2 serum and that the recombinant BmTrx2
      protein could be recognized by serum of B. microti-infected mice.
      Immunofluorescence microscopy showed that BmTrx2 localized in the cell cytoplasm
      of B. microti merozoites in B. microti-infected red blood cells. The results of
      bovine insulin reduction assay indicated the purified recombinant BmTrx2 protein
      possesses antioxidant enzyme activity. Dihydroartemisinin and quinine, known anti
      malaria drugs, and clindamycin, a known anti-babesiosis drug, induced
      significantly higher upregulation of BmTrx2 mRNA. CONCLUSIONS: Our results
      indicate that BmTrx2 is a functional enzyme with antioxidant activity and may be
      involved in the response of B. microti to anti-parasite drugs.

PMID- 29335002
TI  - Leishmania mortality in sand fly blood meal is not species-specific and does not
      result from direct effect of proteinases.
AB  - BACKGROUND: Leishmania development in sand flies is confined to the alimentary
      tract and is closely connected with blood meal digestion. Previously, it has been
      published that activities of sand fly midgut proteases are harmful to Leishmania,
      especially to amastigote-promastigote transition forms. However, our experiments
      with various Leishmania-sand fly pairs gave quite opposite results. METHODS: We
      evaluated the effect of semi-digested midgut content on different life stages of
      Leishmania donovani and Leishmania major in vitro. Various morphological forms of
      parasites, including macrophage-derived amastigotes and transition forms, were
      incubated 2 h with midguts dissected at various intervals (6-72 h) post-blood
      meal or with commercially available proteinase, and their viability was
      determined using flow cytometry. In parallel, using amastigote-initiated
      experimental infections, we compared development of L. donovani in sand flies
      that are either susceptible (Phlebotomus argentipes and P. orientalis) or
      refractory (P. papatasi and Sergentomyia schwetzi) to this parasite. RESULTS: In
      vitro, sand fly midgut homogenates affected L. major and L. donovani in a similar
      way; in all sand fly species, the most significant mortality effect was observed
      by the end of the blood meal digestion process. Surprisingly, the most
      susceptible Leishmania stages were promastigotes, while mortality of transforming
      parasites and amastigotes was significantly lower. Parasites were also
      susceptible to killing by rabbit blood in combination with proteinase, but
      resistant to proteinase itself. In vivo, L. donovani developed late-stage
      infections in both natural vectors; in P. argentipes the development was much
      faster than in P. orientalis. On the other hand, in refractory species P.
      papatasi and S. schwetzi, promastigotes survived activity of digestive enzymes
      but were lost during defecation. CONCLUSIONS: We demonstrated that Leishmania
      transition forms are more resistant to the killing effect of semi-digested blood
      meal than 24 h-old promastigotes. Data suggest that Leishmania mortality is not
      caused directly by sand fly proteases, we assume that this mortality results from
      toxic products of blood meal digestion. Survival of L. donovani promastigotes in
      refractory sand flies until blood meal defecation, together with similar
      mortality of Leishmania parasites incubated in vitro with midgut homogenates of
      susceptible as well as refractory species, contradict the previously raised
      hypotheses about the role of midgut proteases in sand fly vector competence to
      Leishmania.

PMID- 29335003
TI  - Antihypertensive medication adherence and associated factors among adult
      hypertensive patients at Jimma University Specialized Hospital, southwest
      Ethiopia.
AB  - BACKGROUND: Adherence to antihypertensive medications is a key component to
      control blood pressure levels. Poor adherence to these medications leads to the
      development of hypertensive complications and increase risk of cardiovascular
      events which in turn reduces the ultimate clinical outcome. The purpose of this
      study was to assess antihypertensive medication adherence and associated factors
      among adult hypertensive patients. A hospital-based cross-sectional study among
      adult hypertensive patients was conducted at hypertensive follow-up clinic of
      Jimma University Specialized Hospital from March 4, 2015 to April 3, 2015. A
      simple random sampling technique was used to select the study participants from
      the study population. The study patients were interviewed and their medical
      charts were reviewed using a pretested structured questionnaire. Adherence was
      assessed using Morisky Medication Adherence Scale-8 (MMAS-8) and MMAS-8 score
      less than 6 was considered as non-adherent and MMAS-8 score was >= 6 was declared
      as adherence. Factors associated with adherence were identified using binary and
      multivariate logistic regression analysis. Crude odds ratio, adjusted odds ratio
      (AOR) and 95% confidence interval of the odds ratio were calculated using SPSS
      version 21. Variables with p-value less than 0.05 were assumed as statistically
      significant factors. RESULTS: Among 280 hypertensive patients, 61.8% of the study
      participants were found to be adherent. More than half (53.2%) of the
      participants were males and the mean age of the participants was 55.0 +/- 12.7
      years. Co-morbidity (AOR = 0.083, 95% CI = 0.033-0.207, p < 0.001), alcohol
      intake (AOR = 0.011, 95% CI = 0.002-0.079, p < 0.001), getting medications freely
      (AOR = 0.020, 95% CI = 0.003-0.117, p < 0.001), and combination of
      antihypertensive medications (AOR = 0.32, 95% CI = 0.144-0.712, p < 0.005) were
      inversely associated with antihypertensive medication adherence. CONCLUSION: The
      adherence level to the prescribed antihypertensive medications was found to be
      sub-optimal according to the MMAS-8, and influenced by co morbidity, alcohol
      intake, self-purchasing of the medications and combination of antihypertensive
      medications.

PMID- 29335004
TI  - Factors associated with poor treatment outcome of tuberculosis in Debre Tabor,
      northwest Ethiopia.
AB  - OBJECTIVE: Directly observed treatment short course has been implemented as part
      of the national tuberculosis control program in Ethiopia. The strategy, as
      evidenced by different studies, has improved the survival and treatment success
      rate of tuberculosis patients. However, some patients failed to complete their
      treatments and the factors for this failure were not assessed in the study area.
      We, therefore sought to identify factors associated with poor treatment outcome
      of tuberculosis in Debre Tabor, northwest Ethiopia. RESULTS: We included 303
      patients (173 males, 130 females) with mean age of 34.9 years in the study and 39
      (12.9%) patients were with poor treatment outcome over the period of 5 years
      (2008-2013). Being male, urban residency, positive and unknown smear result at
      the 2nd month of treatment and patients in the age of 35-44 years were more
      likely to have poor treatment outcomes than their counterparts. Patients in the
      new treatment category were less likely to have poor treatment outcome compared
      to the retreated cases. Further studies are recommended to explore the
      association of poor treatment outcome with other important factors which are not
      investigated by this study.

PMID- 29335005
TI  - In-depth resistome analysis by targeted metagenomics.
AB  - BACKGROUND: Antimicrobial resistance is a major global health challenge.
      Metagenomics allows analyzing the presence and dynamics of "resistomes" (the
      ensemble of genes encoding antimicrobial resistance in a given microbiome) in
      disparate microbial ecosystems. However, the low sensitivity and specificity of
      available metagenomic methods preclude the detection of minority populations
      (often present below their detection threshold) and/or the identification of
      allelic variants that differ in the resulting phenotype. Here, we describe a
      novel strategy that combines targeted metagenomics using last generation in
      solution capture platforms, with novel bioinformatics tools to establish a
      standardized framework that allows both quantitative and qualitative analyses of
      resistomes. METHODS: We developed ResCap, a targeted sequence capture platform
      based on SeqCapEZ (NimbleGene) technology, which includes probes for 8667
      canonical resistance genes (7963 antibiotic resistance genes and 704 genes
      conferring resistance to metals or biocides), and 2517 relaxase genes (plasmid
      markers) and 78,600 genes homologous to the previous identified targets (47,806
      for antibiotics and 30,794 for biocides or metals). Its performance was compared
      with metagenomic shotgun sequencing (MSS) for 17 fecal samples (9 humans, 8
      swine). ResCap significantly improves MSS to detect "gene abundance" (from 2.0 to
      83.2%) and "gene diversity" (26 versus 14.9 genes unequivocally detected per
      sample per million of reads; the number of reads unequivocally mapped increasing
      up to 300-fold by using ResCap), which were calculated using novel bioinformatic
      tools. ResCap also facilitated the analysis of novel genes potentially involved
      in the resistance to antibiotics, metals, biocides, or any combination thereof.
      CONCLUSIONS: ResCap, the first targeted sequence capture, specifically developed
      to analyze resistomes, greatly enhances the sensitivity and specificity of
      available metagenomic methods and offers the possibility to analyze genes related
      to the selection and transfer of antimicrobial resistance (biocides, heavy
      metals, plasmids). The model opens the possibility to study other complex
      microbial systems in which minority populations play a relevant role.

PMID- 29335007
TI  - Stress-inducible Protein-1 promotes metastasis of gastric cancer via Wnt/beta
      catenin signaling pathway.
AB  - BACKGROUND: Stress-Inducible Protein-1 (STIP1) is a co-chaperone that associates
      directly with heat shock proteins, and regulates motility of various types of
      cancer. In the present study, we investigated the role of STIP1 on metastasis of
      gastric cancer (GC). METHODS: In vivo metastatic experimental model was employed
      to investigate the effect of STIP1 on metastasis of GC cells. Loss-of-function
      and gain-of-function experiments were performed to examine the role of STIP1 on
      metastasis of GC cells. Western blot, immunofluorescence staining, migration and
      invasion assays, microarray and KEGG pathway analysis were applied to explore the
      underlying mechanism. RESULTS: In current study, we demonstrated that STIP1
      promoted lung metastasis of GC cells in vivo. Furthermore, STIP1 significantly
      enhanced migration and invasion abilities of GC cells. In contrast, knock-down of
      STIP1 yielded the opposite effects on these phenotypes in vitro. STIP1 promoted
      tumor metastasis through inducing epithelial-to-mesenchymal transition in GC
      cells. Mechanistically, STIP1 promoted GC metastasis via up-regulation of
      targeted genes in Wnt/beta-catenin signaling pathway, including c-Myc and Cyclin
      D1, and accompanied with nuclear translocation of beta-catenin. CONCLUSIONS: Our
      findings indicate that elevated expression of STIP1 exhibited a metastasis
      promoting effect in GC cells through activation of Wnt/beta-catenin signaling
      pathway. STIP1 may be served as a potential therapeutic target for preventing GC
      metastasis.

PMID- 29335006
TI  - Genetic dissection of the neuro-glio-vascular machinery in the adult brain.
AB  - The adult brain actively controls its metabolic homeostasis via the circulatory
      system at the blood brain barrier interface. The mechanisms underlying the
      functional coupling from neuron to vessel remain poorly understood. Here, we
      established a novel method to genetically isolate the individual components of
      this coupling machinery using a combination of viral vectors. We first discovered
      a surprising non-uniformity of the glio-vascular structure in different brain
      regions. We carried out a viral injection screen and found that intravenous
      Canine Adenovirus 2 (CAV2) preferentially targeted perivascular astrocytes
      throughout the adult brain, with sparing of the hippocampal hilus from infection.
      Using this new intravenous method to target astrocytes, we selectively ablated
      these cells and observed severe defects in hippocampus-dependent contextual
      memory and the metabolically regulated process of hippocampal neurogenesis.
      Combined with AAV9 targeting of neurons and endothelial cells, all components of
      the neuro-glio-vascular machinery can be simultaneously labeled for genetic
      manipulation. Together, we demonstrate a novel method, which we term CATNAP
      (CAV/AAV Targeting of Neurons and Astrocytes Perivascularly), to target and
      manipulate the neuro-glio-vascular machinery in the adult brain.

PMID- 29335009
TI  - Isolated follicle stimulated hormone deficiency in male: case report.
AB  - BACKGROUND: Recent rapid advances in assisted reproductive health technologies
      enables couples with subfertility to conceive through various intervention.
      Majority of treatment modalities target the female partner. However it is
      important to identify and treat male factor subfertility right at the outset. We
      report a case of isolated follicle stimulating hormone deficiency resulting in
      azoospermia and primary subfertility. CASE PRESENTATION: A 28 year otherwise
      healthy male presented with primary subfertility with a healthy female
      counterpart. He was found to have non obstructive azoospermia with low seminal
      fluid volume. He had normal external genitalia and potency with increased libido.
      Further evaluation revealed an isolated deficiency of follicle stimulating
      hormone with elevated testosterone levels. His luteinizing hormone and prolactin
      levels were normal. Contrast enhanced CT scan of chest, abdomen and pelvis and
      MRI scan of the pituitary fossa were normal too. CONCLUSION: In the era of modern
      reproductive technology it is important to further evaluate males with non
      obstructive azoospermia to detect underlying gonadotropin deficiency.

PMID- 29335008
TI  - Multi-omics differentially classify disease state and treatment outcome in
      pediatric Crohn's disease.
AB  - BACKGROUND: Crohn's disease (CD) has an unclear etiology, but there is growing
      evidence of a direct link with a dysbiotic microbiome. Many gut microbes have
      previously been associated with CD, but these have mainly been confounded with
      patients' ongoing treatments. Additionally, most analyses of CD patients'
      microbiomes have focused on microbes in stool samples, which yield different
      insights than profiling biopsy samples. RESULTS: We sequenced the 16S rRNA gene
      (16S) and carried out shotgun metagenomics (MGS) from the intestinal biopsies of
      20 treatment-naive CD and 20 control pediatric patients. We identified the
      abundances of microbial taxa and inferred functional categories within each
      dataset. We also identified known human genetic variants from the MGS data. We
      then used a machine learning approach to determine the classification accuracy
      when these datasets, collapsed to different hierarchical groupings, were used
      independently to classify patients by disease state and by CD patients' response
      to treatment. We found that 16S-identified microbes could classify patients with
      higher accuracy in both cases. Based on follow-ups with these patients, we
      identified which microbes and functions were best for predicting disease state
      and response to treatment, including several previously identified markers. By
      combining the top features from all significant models into a single model, we
      could compare the relative importance of these predictive features. We found that
      16S-identified microbes are the best predictors of CD state whereas MGS
      identified markers perform best for classifying treatment response. CONCLUSIONS:
      We demonstrate for the first time that useful predictors of CD treatment response
      can be produced from shotgun MGS sequencing of biopsy samples despite the
      complications related to large proportions of host DNA. The top predictive
      features that we identified in this study could be useful for building an
      improved classifier for CD and treatment response based on sufferers' microbiome
      in the future. The BISCUIT project is funded by a Clinical Academic Fellowship
      from the Chief Scientist Office (Scotland)-CAF/08/01.

PMID- 29335010
TI  - Acute intestinal obstruction due to extrinsic compression by previa myoma and
      ectopic pregnancy: a case report.
AB  - BACKGROUND: Acute intestinal obstruction during pregnancy is a rare digestive
      surgical emergency with significant maternal and fetal mortality. Diagnosis is
      difficult, often delaying the management. Here, we report an exceptional
      association of mechanical acute intestinal obstruction due to compression by
      previa uterine leiomyoma, and a ruptured ectopic pregnancy. CASE PRESENTATION:
      This is the case report of a 43-year-old primiparous black woman from a rural
      area, who was admitted to the surgical emergency department for acute intestinal
      obstruction. At examination on admittance, our patient had a bad general
      condition with clinical anemia. She had an occlusive syndrome that had been
      evolving for 3 days. A physical examination of her abdomen showed a widespread
      distension with an irregular and polylobed solid mass occupying the whole of the
      lower-umbilical and hypogastric area. A rectal examination found an empty rectum,
      and the mass was perceptible in Douglas's pouch. At the vaginal examination, we
      found the same mass and a finger holster was clean. The diagnosis of intestinal
      occlusion by a tumor was retained. The laparotomy revealed a distended intestine,
      a ruptured right tubal ectopic pregnancy and a polymyomatous uterus. The most
      massive previa leiomyoma was adhering and compressing the rectal and sigmoidal
      hinge. A total hysterectomy was performed and histopathological examination of
      specimens confirmed myoma and ectopic pregnancy. The surgical follow-up was
      uneventful, and our patient was discharged on postoperative day 12. CONCLUSIONS:
      The etiological diagnosis of acute intestinal obstruction during pregnancy is not
      easy, especially in the context of a low-income country where the means of
      biological and radiological diagnosis are lacking. A laparotomy is required
      before diagnosis of acute surgical abdomen and its management will depend on the
      intraoperative findings and the condition of the patient.

PMID- 29335011
TI  - Generalized estimation of the ventilatory distribution from the multiple-breath
      washout: a bench evaluation study.
AB  - BACKGROUND: The multiple-breath washout (MBW) is able to provide information
      about the distribution of ventilation-to-volume (v/V) ratios in the lungs.
      However, the classical, all-parallel model may return skewed results due to the
      mixing effect of a common dead space. The aim of this work is to examine whether
      a novel mathematical model and algorithm is able to estimate v/V of a physical
      model, and to compare its results with those of the classical model. The novel
      model takes into account a dead space in series with the parallel ventilated
      compartments, allows for variable tidal volume (VT) and end-expiratory lung
      volume (EELV), and does not require a ideal step change of the inert gas
      concentration. METHODS: Two physical models with preset v/V units and a common
      series dead space (vd) were built and mechanically ventilated. The models
      underwent MBW with N2 as inert gas, throughout which flow and N2 concentration
      signals were acquired. Distribution of v/V was estimated-via nonnegative least
      squares, with Tikhonov regularization-with the classical, all-parallel model
      (with and without correction for non-ideal inspiratory N2 step) and with the new,
      generalized model including breath-by-breath vd estimates given by the Fowler
      method (with and without constrained VT and EELV). RESULTS: The v/V distributions
      estimated with constrained EELV and VT by the generalized model were practically
      coincident with the actual v/V distribution for both physical models. The v/V
      distributions calculated with the classical model were shifted leftwards and
      broader as compared to the reference. CONCLUSIONS: The proposed model and
      algorithm provided better estimates of v/V than the classical model, particularly
      with constrained VT and EELV.

PMID- 29335012
TI  - The polycomb group protein EZH2 induces epithelial-mesenchymal transition and
      pluripotent phenotype of gastric cancer cells by binding to PTEN promoter.
AB  - BACKGROUND: The influences of oncogenic Ezh2 on the progression and prognosis of
      gastric cancer (GC) and the underlying mechanisms are still poorly understood.
      Here, we aimed at investigating clinicopathological significance of Ezh2 in GC
      and the mechanisms underlying its function in GC development. METHODS: The
      expression level of Ezh2 was determined by qRT-PCR, immunoblot, and
      immunohistochemistry analysis in 156 pairs of GC tissues and adjacent normal
      gastric mucosa tissues. The biological functions of Ezh2 were assessed by in
      vitro and in vivo functional experiments. Chromatin immunoprecipitation (ChIP),
      luciferase, and Western blotting analyses were utilized to identify the
      relationship between Ezh2 and the PTEN/Akt signaling. RESULTS: The expression of
      Ezh2 was higher in gastric cancer tissues in comparison with para-nontumorous
      epithelium. High expression of Ezh2 was associated with more aggressive
      biological behavior and poor prognosis in GC. In vitro studies indicated that
      Ezh2 promoted GC cells' proliferation and clonogenicity. Besides, Ezh2 led to the
      acquisition of epithelial-mesenchymal transition (EMT) phenotype of GC cells and
      enhanced GC cell migration and invasion capacity. In particular, Ezh2
      strengthened sphere-forming capacity of GC cells, indicating its role in the
      enrichment of GC stem cells. Furthermore, we found that PTEN/Akt signaling
      contributed to the effects of Ezh2 on cancer stem cells (CSC) and EMT phenotype
      in GC cells, and blocking PTEN signaling significantly rescued the effects of
      Ezh2. CONCLUSIONS: Taken together, Ezh2 has a central role in regulating diverse
      aspects of the pathogenesis of GC in part by involving PTEN/Akt signaling,
      indicating that it could be an independent prognostic factor and potential
      therapeutic target.

PMID- 29335013
TI  - FIT for FUNCTION: study protocol for a randomized controlled trial.
AB  - BACKGROUND: The current state of evidence suggests that community-based exercise
      programs are beneficial in improving impairment, function, and health status, and
      are greatly needed for persons with stroke. However, limitations of these studies
      include risk of bias, feasibility, and cost issues. METHODS/DESIGN: This single
      blinded, randomized controlled trial (RCT) of 216 participants with stroke will
      compare the effectiveness of a 12-week YMCA community-based wellness program (FIT
      for FUNCTION) specifically designed for community-dwelling persons with stroke to
      persons who receive a standard YMCA membership. The primary outcome will be
      community reintegration using the Reintegration to Normal Living Index at 12 and
      24 weeks. Secondary outcomes include measurement of physical activity level using
      the Rapid Assessment of Physical Activity and accelerometry; balance using the
      Berg Balance Scale; lower extremity function using the Short Physical Performance
      Battery; exercise capacity using the 6-min walk test; grip strength and isometric
      knee extension strength using hand held dynamometry; and health-related quality
      of life using the European Quality of Life 5-Dimension Questionnaire. We are also
      assessing cardiovascular health and lipids; glucose and inflammatory markers will
      be collected following 12-h fast for total cholesterol, insulin, glucose, and
      glycated hemoglobin. Self-efficacy for physical activity will be assessed with a
      single question and self-efficacy for managing chronic disease will be assessed
      using the Stanford 6-item Scale. The Patient Activation Measure will be used to
      assess the patient's level of knowledge, skill, and confidence for self
      management. Healthcare utilization and costs will be evaluated. Group, time, and
      group * time interaction effects will be estimated using generalized linear
      models for continuous variables, including relevant baseline variables as
      covariates in the analysis that differ appreciably between groups at baseline.
      Cost data will be treated as non-parametric and analyzed using a Mann-Whitney U
      test. DISCUSSION: This is a RCT with broad study eligibility criteria intended to
      recruit a wide spectrum of individuals living in the community with stroke. If
      positive benefits are demonstrated, results will provide strong research evidence
      to support the implementation of structured, community-based exercise and
      education/self-management programs for a broad range of people living in the
      community with stroke. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02703805 .
      Registered on 14 October 2014.

PMID- 29335014
TI  - Cost-effectiveness study of early versus late parenteral nutrition in critically
      ill children (PEPaNIC): preplanned secondary analysis of a multicentre randomised
      controlled trial.
AB  - BACKGROUND: The multicentre randomised controlled PEPaNIC trial showed that
      withholding parenteral nutrition (PN) during the first week of critical illness
      in children was clinically superior to providing early PN. This study describes
      the cost-effectiveness of this new nutritional strategy. METHODS: Direct medical
      costs were calculated with use of a micro-costing approach. We compared the costs
      of late versus early initiation of PN (n = 673 versus n = 670 patients) in the
      Belgian and Dutch study populations from a hospital perspective, using Student's
      t test with bootstrapping. Main cost drivers were identified and the impact of
      new infections on the total costs was assessed. RESULTS: Mean direct medical
      costs for patients receiving late PN (?26.680, IQR ?10.090-28.830 per patient)
      were 21% lower (-?7.180, p = 0.007) than for patients receiving early PN
      (?33.860, IQR ?11.080-34.720). Since late PN was more effective and less costly,
      this strategy was superior to early PN. The lower costs for PN only contributed
      2.1% to the total cost reduction. The main cost driver was intensive care
      hospitalisation costs (-?4.120, p = 0.003). The patients who acquired a new
      infection (14%) were responsible for 41% of the total costs. Sensitivity analyses
      confirmed consistency across both healthcare systems. CONCLUSIONS: Late
      initiation of PN decreased the direct medical costs for hospitalisation in
      critically ill children, beyond the expected lower costs for withholding PN.
      Avoiding new infections by late initiation of PN yielded a large cost reduction.
      Hence, late initiation of PN was superior to early initiation of PN largely via
      its effect on new infections. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01536275
      . Registered on 16 February 2012.

PMID- 29335015
TI  - Cryptic diversity in an Atlantic Forest malaria vector from the mountains of
      South-East Brazil.
AB  - BACKGROUND: Anopheles (Kerteszia) cruzii is the primary vector of human and
      simian malarias in Brazilian regions covered by the Atlantic Rainforest. Previous
      studies found that An. cruzii presents high levels of behavioural, chromosomal
      and molecular polymorphisms, which led to the hypothesis that it may be a complex
      of cryptic species. Here, An. cruzii specimens were collected in five sites in
      South-East Brazil located at different altitudes on the inner and coastal slopes
      of two mountain ranges covered by Atlantic Rainforest, known as Serra do Mar and
      Serra da Mantiqueria. Partial sequences for two genes (Clock and cpr) were
      generated and compared with previously published sequences from Florianopolis
      (southern Brazil). Genetic diversity was analysed with estimates of population
      structure (F ST ) and haplotype phylogenetic trees in order to understand how
      many species of the complex may occur in this biome and how populations across
      the species distribution are related. RESULTS: The sequences from specimens
      collected at sites located on the lower coastal slopes of Serra do Mar
      (Guapimirim, Tingua and Sana) clustered together in the phylogenetic analysis,
      while the major haplotypes from sites located on higher altitude and at the
      continental side of the same mountains (Bocaina) clustered with those from Serra
      da Mantiqueira (Itatiaia), an inner mountain range. These two An. cruzii lineages
      showed statistically significant genetic differentiation and fixed characters,
      and have high F ST values typical of between species comparisons. Finally, in
      Bocaina, where the two lineages occur in sympatry, we found deviations from Hardy
      Weinberg equilibrium due to a deficit of heterozygotes, indicating partial
      reproductive isolation. These results strongly suggest that at least two distinct
      lineages of An. cruzii (provisorily named "Group 1" and "Group 2") occur in the
      mountains of South-East Brazil. CONCLUSIONS: At least two genetically distinct
      An. cruzii lineages occur in the Atlantic Forest covered mountains of South-East
      Brazil. The co-occurrence of distinct lineages of An. cruzii (possibly incipient
      species) in those mountains is an interesting biological phenomenon and may have
      important implications for malaria prevalence, Plasmodium transmission dynamics
      and control.

PMID- 29335016
TI  - Autophagy is required for human umbilical cord mesenchymal stem cells to improve
      spatial working memory in APP/PS1 transgenic mouse model.
AB  - BACKGROUND: Recent studies have shown that autophagy plays a central role in
      mesenchymal stem cells (MSCs), and many studies have shown that human umbilical
      cord MSCs (huMSCs) can treat Alzheimer's disease (AD) through a variety of
      mechanisms. However, no studies have looked at the effects of autophagy on
      neuroprotective function of huMSCs in the AD mouse model. Thus, in this study we
      investigated whether inhibition of autophagy could weaken or block the function
      of huMSCs through in vitro and in vivo experiments. METHODS: In vitro we examined
      huMSC migration and neuronal differentiation by inhibiting or activating
      autophagy; in vivo autophagy of huMSCs was inhibited by knocking down Beclin 1,
      and these huMSCs were transplanted into the APP/PS1 transgenic mouse. A series of
      related indicators were detected by T-maze task, electrophysiological
      experiments, immunofluorescence staining, enzyme-linked immunosorbent assay
      (ELISA), and Western blotting. RESULTS: We demonstrated that regulation of
      autophagy can affect huMSC migration and their neuronal differentiation.
      Moreover, inhibition of autophagy in huMSCs could not realize neuroprotective
      effects via anti-apoptosis or promoting neurogenesis and synapse formation
      compared with those of control huMSCs. CONCLUSIONS: These findings indicate that
      autophagy is required for huMSCs to maintain their function and improve cognition
      impairment in APP/PS1 transgenic mice.

PMID- 29335017
TI  - Effect of laparoscopy by single-port endoscopic access in benign adnexal surgery:
      study protocol for a randomized controlled trial.
AB  - BACKGROUND: Laparoscopic surgery has become the preferred surgical approach due
      to a reduction in postoperative pain, better recovery, shorter hospitalization,
      and improved esthetic outcomes. Laparoscopic surgery with single-port laparoscopy
      (SPL) is a laparoscopic surgery technique that is based on making a single
      parietal incision using a single trocar specifically designed to allow
      introduction of several instruments. The level of evidence regarding the
      advantages of SPL in terms of postoperative pain has remained low despite several
      randomized studies. Adult patients exhibiting a surgical indication for an a
      priori benign ovarian pathology or for prophylactic purposes that can be
      performed by laparoscopy will be randomized to receive conventional laparoscopy
      (CL) or SPL. The aim of our study is to evaluate whether SPL offers advantages
      over CL in benign adnexal surgery. METHODS: The patients will be evaluated
      preoperatively to confirm their eligibility. The perioperative data up to 24 h
      after the intervention, as well as the postoperative data at day 7 and at one
      month from the intervention will be collected. The primary outcome for the study
      will be the postoperative pain at 24 h +/- 2 h after the intervention. The pain
      will be assessed by a numeric rating scale of 0-10. Other outcomes will also be
      assessed, such as pain at other times, the consumption of analgesics, the
      operative time, perioperative bleeding, the number of additional trocars in the
      two groups, the incidence of laparoconversion, the esthetic criteria of the scar
      at one month, the incidence of complications, and the quality of life at one
      month. DISCUSSION: If our hypothesis is confirmed, this study will provide
      evidence that the use of SPL can decrease postoperative pain in adnexal surgery.
      The standard surgical treatment of this condition would thus be modified. TRIAL
      REGISTRATION: ClinicalTrials.gov, NCT02739724 . Registered on 12 April 2016.

PMID- 29335018
TI  - Danggwijagyaksan for climacteric syndrome in peri- and postmenopausal women with
      a blood-deficiency dominant pattern: study protocol for a randomized, double
      blind, placebo-controlled pilot trial.
AB  - BACKGROUND: This study aims to explore the safety, efficacy, and feasibility of
      Danggwijagyaksan (DJS) for alleviating climacteric syndrome in peri- and
      postmenopausal women with a blood-deficiency dominant pattern. METHODS/DESIGN:
      This is a randomized, double-blind, placebo-controlled pilot clinical trial. A
      total of 34 women with climacteric syndrome who have signed informed consent
      forms will be registered in this study. Placebo or DJS will be randomly assigned
      to the participants in an equal proportion. The participants will visit the
      clinical trial center every 2 weeks and receive placebo or DJS granules. The
      treatment period is 4 weeks and the administration frequency is three times
      daily. Data will be collected from the participants at baseline, at week 5, and
      at week 9 after random allocation. The primary outcome measure will be the mean
      change in the Menopause Rating Scale from baseline to week 5. Secondary outcome
      measures will include the World Health Organization Quality of Life-BREF (WHOQOL
      BREF) score, the Blood Deficiency Scoring System score, lean body mass, and blood
      tests, including serum follicle-stimulating hormone and estradiol concentration.
      To assess the safety of DJS, a laboratory test will be conducted before and after
      treatment and the participants will be asked about any occurrence of adverse
      events every visit. The recruitment rate, completion rate, and medication
      adherence will also be calculated, to assess feasibility. DISCUSSION: The
      findings of this study will provide the basis for a full-scale randomized
      controlled trial to confirm the safety and efficacy of DJS for the treatment of
      climacteric syndrome in peri- and postmenopausal women. TRIAL REGISTRATION:
      Clinical Research Information Service (CRIS), Republic of Korea, KCT0002387 .
      Registered on 25 July 2017.

PMID- 29335019
TI  - Patient blood management programs: how to spread the word?
AB  - Red blood cell (RBC) transfusions save lives and improve health; however,
      unnecessary transfusion practice exposes patients to immediate and long-term
      negative consequences. Indirect consequences of unnecessary transfusions are the
      reduced availability of RBC units for patients who are in need. Accumulating
      evidence shows that restricting RBC transfusions improves outcomes and current
      guidelines suggest limiting RBC transfusion to the minimum number of units
      required to relieve symptoms of anemia or to return the patient to a safe
      hemoglobin range (7-8 g/dl in stable, non-cardiac inpatients). Still, studies
      show that there is over-utilization of RBC transfusion, partly due to low level
      of knowledge of physicians regarding restrictive RBC transfusion policy across a
      broad range of professions and specialties. Patient blood management (PBM)
      programs have been developed to promote clear hospital transfusion guidelines,
      strive for optimization of patient hemoglobin and iron stores and, most
      importantly, improve education regarding restrictive RBC policy. Understanding
      what and where the gaps of knowledge are, as was done in the study by Dr. Koren
      and his colleagues, is an important step for developing effective PBM programs.

PMID- 29335020
TI  - Ensemble genomic analysis in human lung tissue identifies novel genes for chronic
      obstructive pulmonary disease.
AB  - BACKGROUND: Genome-wide association studies (GWAS) have identified single
      nucleotide polymorphisms (SNPs) significantly associated with chronic obstructive
      pulmonary disease (COPD). However, many genetic variants show suggestive evidence
      for association but do not meet the strict threshold for genome-wide
      significance. Integrative analysis of multiple omics datasets has the potential
      to identify novel genes involved in disease pathogenesis by leveraging these
      variants in a functional, regulatory context. RESULTS: We performed expression
      quantitative trait locus (eQTL) analysis using genome-wide SNP genotyping and
      gene expression profiling of lung tissue samples from 86 COPD cases and 31
      controls, testing for SNPs associated with gene expression levels. These results
      were integrated with a prior COPD GWAS using an ensemble statistical and network
      methods approach to identify relevant genes and observe them in the context of
      overall genetic control of gene expression to highlight co-regulated genes and
      disease pathways. We identified 250,312 unique SNPs and 4997 genes in the
      cis(local)-eQTL analysis (5% false discovery rate). The top gene from the
      integrative analysis was MAPT, a gene recently identified in an independent GWAS
      of lung function. The genes HNRNPAB and PCBP2 with RNA binding activity and the
      gene ACVR1B were identified in network communities with validated disease
      relevance. CONCLUSIONS: The integration of lung tissue gene expression with
      genome-wide SNP genotyping and subsequent intersection with prior GWAS and omics
      studies highlighted candidate genes within COPD loci and in communities harboring
      known COPD genes. This integration also identified novel disease genes in sub
      threshold regions that would otherwise have been missed through GWAS.

PMID- 29335022
TI  - Tackling the challenges of matching biomedical ontologies.
AB  - BACKGROUND: Biomedical ontologies pose several challenges to ontology matching
      due both to the complexity of the biomedical domain and to the characteristics of
      the ontologies themselves. The biomedical tracks in the Ontology Matching
      Evaluation Initiative (OAEI) have spurred the development of matching systems
      able to tackle these challenges, and benchmarked their general performance. In
      this study, we dissect the strategies employed by matching systems to tackle the
      challenges of matching biomedical ontologies and gauge the impact of the
      challenges themselves on matching performance, using the AgreementMakerLight
      (AML) system as the platform for this study. RESULTS: We demonstrate that the
      linear complexity of the hash-based searching strategy implemented by most state
      of-the-art ontology matching systems is essential for matching large biomedical
      ontologies efficiently. We show that accounting for all lexical annotations
      (e.g., labels and synonyms) in biomedical ontologies leads to a substantial
      improvement in F-measure over using only the primary name, and that accounting
      for the reliability of different types of annotations generally also leads to a
      marked improvement. Finally, we show that cross-references are a reliable source
      of information and that, when using biomedical ontologies as background
      knowledge, it is generally more reliable to use them as mediators than to perform
      lexical expansion. CONCLUSIONS: We anticipate that translating traditional
      matching algorithms to the hash-based searching paradigm will be a critical
      direction for the future development of the field. Improving the evaluation
      carried out in the biomedical tracks of the OAEI will also be important, as
      without proper reference alignments there is only so much that can be ascertained
      about matching systems or strategies. Nevertheless, it is clear that, to tackle
      the various challenges posed by biomedical ontologies, ontology matching systems
      must be able to efficiently combine multiple strategies into a mature matching
      approach.

PMID- 29335021
TI  - Seroprevalence of dengue among healthy adults in a rural community in Southern
      Malaysia: a pilot study.
AB  - BACKGROUND: The frequency and magnitude of dengue epidemics continue to increase
      exponentially in Malaysia, with a shift in the age range predominance toward
      adults and an expansion to rural areas. Despite this, information pertaining to
      the extent of transmission of dengue virus (DENV) in the rural community is
      lacking. This community-based pilot study was conducted to establish DENV
      seroprevalence amongst healthy adults in a rural district in Southern Malaysia,
      and to identify influencing factors. METHODS: In this study undertaken between
      April and May 2015, a total of 277 adult participants were recruited from
      households across three localities in the Sungai Segamat subdistrict in Segamat
      district. Sera were tested for immunoglobulin G (IgG) (Panbio(r) Dengue Indirect
      IgG ELISA/high-titer capture) and immunoglobulin M (IgM) (Panbio(r)) antibodies.
      The plaque reduction neutralization test (PRNT) was conducted on random samples
      of IgG-positive sera for further confirmation. Medical history and a recall of
      previous history of dengue were collected through interviews, whereas
      sociodemographic information was obtained from an existing database. RESULTS: The
      overall seroprevalence for DENV infection was 86.6% (240/277) (95% CI: 83-91%).
      Serological evidence of recent infection (IgM/high-titer capture IgG) was noted
      in 11.2% (31/277) of participants, whereas there was evidence of past infection
      in 75.5% (209/277) of participants (indirect IgG minus recent infections). The
      PRNT assay showed that the detected antibodies were indeed specific to DENV. The
      multivariate analysis showed that the older age group was significantly
      associated with past DENV infections. Seropositivity increased with age; 48.5% in
      the age group of <25 years to more than 85% in age group of >45 years (P <
      0.001). No associations with occupation, study site, housing type, comorbidity,
      educational level, and marital status were observed, although the latter two were
      statistically significant in the univariate analysis. None of the studied factors
      were significantly associated with recent DENV infections in the multivariate
      analysis, although there was a pattern suggestive of recent outbreak in two study
      sites populated predominately by Chinese people. The majority of infections did
      not give rise to recognizable disease (either asymptomatic or nonspecific
      symptoms) as only 12.9% of participants (31/240) recalled having dengue in the
      past. CONCLUSIONS: The predominantly rural community under study had a very high
      previous exposure to dengue. The finding of a high proportion of unreported cases
      possibly due to subclinical infections underscores the need for enhanced
      surveillance and control methods. This finding also has implications for
      measuring disease burden, understanding transmission dynamics, and hypothesizing
      effects on DENV vaccine efficacy and uptake.

PMID- 29335023
TI  - Early neonatal Glutaric aciduria type I hidden by perinatal asphyxia: a case
      report.
AB  - BACKGROUND: Perinatal asphyxia (PA) occurs in about 2 to 10 per 1000 live full
      term births. Although neonatal epileptic seizures are observed in up to 60% of
      cases, PA may mimic or subtend other conditions. Hypoxia related brain injury is
      particularly relevant, as it may have permanent effects on neuropsychomotor
      development. Antepartum obstetric conditions, may, in turn, lead to hypoxic
      ischemic damage to the fetus and the newborn, often underlying PA. Herein, a case
      of PA that hid and triggered signs and symptoms of Glutaric Aciduria type I (GA
      I), is reported. CASE PRESENTATION: R.F. was born at term after prolonged labour,
      by induced vaginal delivery with the Kristeller manoeuvre. He presented with
      severe asphyxia and asystoly. Immediate cardiopulmonary resuscitation promptly
      restored cardiorespiratory parameters, allowing for early extubation 30 min
      after. During the following hours, severe axial muscle hypotonia with an
      increased tone of the limb extensor muscles became evident. The absence of crying
      and archaic reflexes persisted and there was an onset of generalized tonic or
      clonic seizure. First level metabolic and inflammatory markers were within the
      normal range. An inherited metabolic disease was then suspected, due to the
      persistent clinical signs of severe neurological damage without any detectable
      septic parameter. GA-I was assessed and specific treatment started without any
      clinical improvement, although ensuring adequate growth and metabolic control.
      Thereafter, the baby developed a severe encephalopathy with drug resistant
      epileptic seizures. The progression of the neurological damage and a CVC-related
      sepsis led him to exitus at 2 years. CONCLUSIONS: To the best of our knowledge,
      this is the first case of early post-natal onset of GA-I reported in literature
      to date, in the absence of expanded newborn screening (NBS) programme. As
      expanded NBS programmes for inborn errors of metabolism have not yet been
      internationally adopted, we are of the opinion that such diseases may well be
      hidden by misleading signs and symptoms imputable to other more frequent harmful
      clinical conditions. Moreover, it would be advisable that neonatologists be
      trained to include GA-I in the differential diagnosis of neurological damage
      secondary to PA.

PMID- 29335025
TI  - Prevalence of a carbapenem-resistance gene (KPC), vancomycin-resistance genes
      (van A/B) and a methicillin-resistance gene (mecA) in hospital and municipal
      sewage in a southwestern province of Saudi Arabia.
AB  - OBJECTIVE: According to the World Health Organization, the increasing antibiotic
      resistance of pathogens is one of the most important threats to human health.
      Prevalence of a carbapenem-resistance gene (KPC), vancomycin-resistance genes
      (van A/B) and a methicillin-resistance gene (mecA) in hospital and municipal
      sewages will be potential threat to public health. RESULTS: Vancomycin-resistance
      genes were detected in the sewage of community tank-II, sewage tank of the
      tertiary and general hospital. Carbapenem-resistance gene was detected in sewage
      of community tank-II and sewage from tertiary hospital. Methicillin-resistance
      gene was detected in sewage of community tank-II, sewage from a fish market
      sewage tank and sewage from an animal slaughter house sewage tank. The detection
      of a KPC, van A/B and a mecA in sewages will help further the process to take the
      appropriate measures to prevent the spread of such bacteria in the environment.

PMID- 29335024
TI  - Sex differences in the late first trimester human placenta transcriptome.
AB  - BACKGROUND: Development of the placenta during the late first trimester is
      critical to ensure normal growth and development of the fetus. Developmental
      differences in this window such as sex-specific variation are implicated in later
      placental disease states, yet gene expression at this time is poorly understood.
      METHODS: RNA-sequencing was performed to characterize the transcriptome of 39
      first trimester human placentas using chorionic villi following genetic testing
      (17 females, 22 males). Gene enrichment analysis was performed to find enriched
      canonical pathways and gene ontologies in the first trimester. DESeq2 was used to
      find sexually dimorphic gene expression. Patient demographics were analyzed for
      sex differences in fetal weight at time of chorionic villus sampling and birth.
      RESULTS: RNA-sequencing analyses detected 14,250 expressed genes, with chromosome
      19 contributing the greatest proportion (973/2852, 34.1% of chromosome 19 genes)
      and Y chromosome contributing the least (16/568, 2.8%). Several placenta-enriched
      genes as well as histone-coding genes were identified to be unique to the first
      trimester and common to both sexes. Further, we identified 58 genes with
      significantly different expression between males and females: 25 X-linked, 15 Y
      linked, and 18 autosomal genes. Genes that escape X inactivation were highly
      represented (59.1%) among X-linked genes upregulated in females. Many genes
      differentially expressed by sex consisted of X/Y gene pairs, suggesting that
      dosage compensation plays a role in sex differences. These X/Y pairs had roles in
      parallel, ancient canonical pathways important for eukaryotic cell growth and
      survival: chromatin modification, transcription, splicing, and translation.
      CONCLUSIONS: This study is the first characterization of the late first trimester
      placenta transcriptome, highlighting similarities and differences among the sexes
      in ongoing human pregnancies resulting in live births. Sexual dimorphism may
      contribute to pregnancy outcomes, including fetal growth and birth weight, which
      was seen in our cohort, with males significantly heavier than females at birth.
      This transcriptome provides a basis for development of early diagnostic tests of
      placental function that can indicate overall pregnancy heath, fetal-maternal
      health, and long-term adult health.

PMID- 29335026
TI  - Congenital anomalies in neurofibromatosis 1: a retrospective register-based total
      population study.
AB  - BACKGROUND: Neurofibromatosis type 1 (NF1) is a dominantly inherited Rasopathy
      caused by mutations in the NF1 gene on chromosome 17. NF1 has been connected to
      congenital anomalies, e.g., in the skeletal and cardiovascular systems, but the
      overall incidence of anomalies is unknown. In this retrospective register-based
      total population study conducted in Finland, the congenital anomalies in NF1 were
      evaluated. METHODS: One thousand four hundred ten patients with NF1 were
      identified by searching the medical records related to inpatient and outpatient
      hospital visits of patients with an associated diagnosis for NF1 in 1987-2011.
      Each diagnosis was confirmed by a thorough review of the medical records. Ten non
      NF1 control persons per NF1 patient were collected from the Population Register
      Centre. NF1 patients and controls were linked to the Medical Birth Register and
      the Register of Congenital Malformations. Odds ratios (OR) and 95% confidence
      intervals (95% CI) for major congenital anomalies (MCA) were calculated. RESULTS:
      The OR for at least one MCA among NF1 children was almost threefold (adjusted OR
      2.78, 95% CI 1.71-4.54) compared to controls matched for age, sex and
      municipality. NF1 children had a significantly increased risk of congenital
      anomalies in the circulatory (adjusted OR 3.35, 95% CI 1.64-6.83), urinary
      (adjusted OR 4.26, 95% CI 1.36-13.35) and musculoskeletal (adjusted OR 2.77, 95%
      CI 1.09-7.02) systems. Also, anomalies of the eye, ear, head and neck were more
      common among NF1 children than controls (adjusted OR 4.66, 95% CI 1.42-15.31).
      Non-NF1 children of mothers with NF1 did not have more anomalies than controls
      (adjusted OR 0.53, 95% CI 0.13-2.21). CONCLUSIONS: Children with NF1 have more
      MCAs than controls and close follow-up during pregnancy and the neonatal period
      is required if the mother or father has NF1. Non-NF1 children of mothers with NF1
      do not have an increased risk for anomalies.

PMID- 29335028
TI  - Towards a 21st century health care system: advancing the case for telecare.
AB  - Telecare is increasingly recognized as an essential tool for a contemporary
      twenty-first century health care system even though the evidence is still
      emerging on its effectiveness. The need to find delivery models like telecare
      that improve both the convenience and value of care is universal, but
      particularly pressing for countries like the U.S. and Israel who are facing
      rising costs related to the needs of individuals with multiple complex
      conditions. This commentary provides highlights of the current state of practice
      and policy for telecare and the challenges that remain ahead as it is adopted
      into the mainstream.

PMID- 29335027
TI  - Fungi stabilize connectivity in the lung and skin microbial ecosystems.
AB  - BACKGROUND: No microbe exists in isolation, and few live in environments with
      only members of their own kingdom or domain. As microbiome studies become
      increasingly more interested in the interactions between microbes than in
      cataloging which microbes are present, the variety of microbes in the community
      should be considered. However, the majority of ecological interaction networks
      for microbiomes built to date have included only bacteria. Joint association
      inference across multiple domains of life, e.g., fungal communities (the
      mycobiome) and bacterial communities, has remained largely elusive. RESULTS:
      Here, we present a novel extension of the SParse InversE Covariance estimation
      for Ecological ASsociation Inference (SPIEC-EASI) framework that allows
      statistical inference of cross-domain associations from targeted amplicon
      sequencing data. For human lung and skin micro- and mycobiomes, we show that
      cross-domain networks exhibit higher connectivity, increased network stability,
      and similar topological re-organization patterns compared to single-domain
      networks. We also validate in vitro a small number of cross-domain interactions
      predicted by the skin association network. CONCLUSIONS: For the human lung and
      skin micro- and mycobiomes, our findings suggest that fungi play a stabilizing
      role in ecological network organization. Our study suggests that computational
      efforts to infer association networks that include all forms of microbial life,
      paired with large-scale culture-based association validation experiments, will
      help formulate concrete hypotheses about the underlying biological mechanisms of
      species interactions and, ultimately, help understand microbial communities as a
      whole.

PMID- 29335029
TI  - Estimating the proportion of clinically diagnosed infectious and non-infectious
      animal diseases in Ganta Afeshum woreda, Eastern Tigray zone, Ethiopia.
AB  - OBJECTIVE: This study was performed with the objective of identifying the
      proportion of emerging and endemic livestock diseases using cross sectional
      survey. RESULT: A total of 285 clinically diseased animals were presented to a
      veterinary clinic and diagnosed tentatively based on history, clinical sign, and
      simple laboratory diagnostics and from the study, actinomycosis (15.83%),
      mastitis (15%), tick infestation (10%), respiratory diseases (9.16%) and gastro
      intestinal parasitism (9.16%) were confirmed with higher proportion in large
      animals. Pasteurollosis (38, 31%), contagious ecthyma (12, 10%), tick infestation
      (9, 0%), mite infestation (9, 10%), sheep and goat pox (9, 10%), and
      gastrointestinal parasitism (9, 17%) were frequently encountered diseases in
      sheep and goat respectively. In equids, back sore, epizootic lymphangitis and
      lameness accounted a proportion of 22.95, 21.31, and 13.11% respectively. In
      conclusion, result of the present study showed that the proportion of livestock
      disease is high, and it affects the socioeconomic status of the local community
      in the study area as a result of mortality and production loss.

PMID- 29335031
TI  - Respiration pattern variability and related default mode network connectivity are
      altered in remitted depression.
AB  - BACKGROUND: Studies with healthy participants and patients with respiratory
      diseases suggest a relation between respiration and mood. The aim of the present
      analyses was to investigate whether emotionally challenged remitted depressed
      participants show higher respiration pattern variability (RPV) and whether this
      is related to mood, clinical outcome and increased default mode network
      connectivity. METHODS: To challenge participants, sad mood was induced with
      keywords of personal negative life events in individuals with remitted depression
      [recurrent major depressive disorder (rMDD), n = 30] and matched healthy controls
      (HCs, n = 30) during functional magnetic resonance imaging. Respiration was
      measured by means of a built-in respiration belt. Additionally, questionnaires, a
      daily life assessment of mood and a 3 years follow-up were applied. For
      replication, we analysed RPV in an independent sample of 53 rMDD who underwent
      the same fMRI paradigm. RESULTS: During sad mood, rMDD compared with HC showed
      greater RPV, with higher variability in pause duration and respiration frequency
      and lower expiration to inspiration ratio. Higher RPV was related to lower daily
      life mood and predicted higher depression scores as well as relapses during a 3
      year follow-up period. Furthermore, in rMDD compared with HC higher main
      respiration frequency exhibited a more positive association with connectivity of
      the posterior cingulate cortex and the right parahippocampal gyrus. CONCLUSIONS:
      The results suggest a relation between RPV, mood and depression on the
      behavioural and neural level. Based on our findings, we propose interventions
      focusing on respiration to be a promising additional tool in the treatment of
      depression.

PMID- 29335030
TI  - Preschool psychiatric disorders: homotypic and heterotypic continuity through
      middle childhood and early adolescence.
AB  - BACKGROUND: Many preschool-age children meet criteria for psychiatric disorders,
      and rates approach those observed in later childhood and adolescence. However,
      there is a paucity of longitudinal research examining the outcomes of preschool
      diagnoses. METHODS: Families with a 3-year-old child (N = 559) were recruited
      from the community. Primary caregivers were interviewed using the Preschool Age
      Psychiatric Assessment when children were 3 years old (n = 541), and, along with
      children, using the Schedule for Affective Disorders and Schizophrenia for School
      Age Children Present and Lifetime Version when children were 9 and 12 years old.
      RESULTS: Rates of disruptive behavior disorders (DBD) decreased from preschool to
      middle childhood and early adolescence, whereas rates of attention
      deficit/hyperactivity disorder (ADHD) increased. Rates of any psychiatric
      disorder and depression increased from preschool to early adolescence only.
      Preschoolers with a diagnosis were over twice as likely to have a diagnosis
      during later periods. Homotypic continuity was present for anxiety disorders from
      preschool to middle childhood, for ADHD from preschool to early adolescence, and
      for DBD through both later time points. There was heterotypic continuity between
      preschool anxiety and early adolescent depression, and between preschool ADHD and
      early adolescent DBD. Dimensional symptom scores showed homotypic continuity for
      all diagnostic categories and showed a number of heterotypic associations as
      well. CONCLUSIONS: Results provide moderate support for the predictive validity
      of psychiatric disorders in preschoolers. Psychopathology in preschool is a
      significant risk factor for future psychiatric disorders during middle childhood
      and early adolescence.

PMID- 29335033
TI  - Should capacity assessments be performed routinely prior to discussing advance
      care planning with older people?
AB  - : ABSTRACTBackground:People with dementia receive worse end of life care compared
      to those with cancer. Barriers to undertaking advanced care planning (ACP) in
      people with dementia include the uncertainty about their capacity to engage in
      such discussions. The primary aim of this study was to compare the Advance Care
      Planning-Capacity Assessment Vignette tool (ACP-CAV) with a semi-structured
      interview adapted from the MacArthur Competence Assessment Tool-Treatment (MacCAT
      T). The secondary aim was to identify demographic and cognitive functioning
      variables that may predict whether a person has capacity to discuss ACP. METHODS:
      32 older people (mean age = 84.1) with a Mini-Mental State Examination of 24 or
      above were recruited from two retirement villages in Auckland. Participants also
      completed Trail Making Test Part A & Part B and Geriatric Depression Scale (GDS
      15) before undertaking the two capacity assessments that were video recorded to
      enable further analysis by four independent old age psychiatrists. RESULTS: Using
      the MacCAT-T as the gold standard, over half (53.1%) of the participants were
      considered as lacking in capacity to engage in ACP. Participants struggled with
      the "Understanding ACP" domain the most. Capacity was not predictable by any of
      the demographic or cognitive functioning variables. When compared to the gold
      standard, ACP-CAV was accurate in assessing capacity in 68.8% of the cases.
      CONCLUSION: Clinicians should routinely explain ACP to older people and ensure
      they fully understand it prior to an ACP discussion. If there is any concern
      about their understanding, further exploration and documentation of their
      capacity using the capacity assessment framework would be necessary. However,
      capacity assessment is a complex iterative process that does not easily lend
      itself to screening methodology and requires a high level of clinical judgment.

PMID- 29335032
TI  - 'Sit and tilt' preparation for subscapular system free flaps.
AB  - BACKGROUND: The ablation of advanced head and neck cancer often results in large
      three-dimensional defects that require free tissue transfer to optimally address
      functional and cosmetic issues. The subscapular system is a highly versatile
      donor site for flaps used for head and neck reconstruction. Traditional methods
      of harvesting subscapular flaps require repositioning and re-preparing, which
      significantly increases the operative time and prevents simultaneous harvesting
      of the flap. METHOD: This paper presents our experience of a single-stage 'sit
      and tilt' technique, which provides a convenient method for harvesting
      subscapular system free flaps without significant repositioning. RESULTS AND
      CONCLUSION: This technique was used for a variety of head and neck defects, and
      body habitus did not seem to affect free tissue harvesting. It is hoped that
      utilisation of this preparation and harvesting technique will make head and neck
      surgeons more willing to take advantage of the subscapular system.

PMID- 29335034
TI  - Staying Out of the Closet: LGBT Older Adults' Hopes and Fears in Considering End
      of-Life.
AB  - Canada is experiencing population aging, and given the heterogeneity of older
      adults, there is increasing diversity in late life. The purpose of this study was
      to help fill the research gaps on LGBT aging and end-of-life. Through focus
      groups, we sought to better understand the lived experience of older LGBT
      individuals and to examine their concerns associated with end-of-life. Our
      analysis highlights the idea that identifying as LGBT matters when it comes to
      aging and end-of-life care. In particular, gender identity and sexual orientation
      matter when it comes to social connections, in the expectations individuals have
      for their own care, and in the unique fear related to staying out of the closet
      and maintaining identity throughout aging and end-of-life. This study underscores
      the need to consider gender identity and sexual orientation at end-of-life. In
      particular, recognition of intersectionality and social locations is crucial to
      facilitating positive aging experiences and end-of-life care.

PMID- 29335035
TI  - Innovating dementia care; implementing characteristics of green care farms in
      other long-term care settings.
AB  - : ABSTRACTBackground:People with dementia at green care farms (GCFs) are
      physically more active, have more social interactions, are involved in a larger
      variety of activities, and come outdoors more often than those in other long-term
      dementia care settings. These aspects may positively affect health and well
      being. This study explored which and how characteristics of GCFs could be
      implemented in other long-term dementia care settings, taking into account
      possible facilitators and barriers. METHODS: Semi-structured interviews were
      conducted with 23 professionals from GCFs, independent small-scale long-term care
      facilities, and larger scale long-term care facilities in the Netherlands. The
      framework method was used to analyze the data. RESULTS: Several characteristics
      of GCFs (e.g. homelike aspects, domestic activities, and access to outdoor
      environments) have already been applied in other types of long-term dementia care
      settings. However, how and the extent to which these characteristics are being
      applied differ between GCFs and other types of long-term dementia care settings.
      Facilitators and barriers for the implementation of characteristics of GCFs were
      related to the physical environment in which the care facility is situated (e.g.
      the degree of urbanization), characteristics and competences of staff members
      (e.g. flexibility, creativity), characteristics and competences of managers (e.g.
      leadership, vision), and the political context (e.g. application of risk and
      safety protocols). CONCLUSION: Several characteristics can be implemented in
      other dementia care settings. However, to realize innovation in dementia care it
      is important that not only the physical environment but also the social and
      organizational environments are supporting the process of change.

PMID- 29335036
TI  - Individuals with currently untreated mental illness: causal beliefs and readiness
      to seek help.
AB  - AIMS: Many people with mental illness do not seek professional help. Beliefs
      about the causes of their current health problem seem relevant for initiating
      treatment. Our aim was to find out to what extent the perceived causes of current
      untreated mental health problems determine whether a person considers
      herself/himself as having a mental illness, perceives need for professional help
      and plans to seek help in the near future. METHODS: In a cross-sectional study,
      we examined 207 untreated persons with a depressive syndrome, all fulfilling
      criteria for a current mental illness as confirmed with a structured diagnostic
      interview (Mini International Neuropsychiatric Interview). The sample was
      recruited in the community using adverts, flyers and social media. We elicited
      causal explanations for the present problem, depression literacy, self
      identification as having a mental illness, perceived need for professional help,
      help-seeking intentions, severity of depressive symptoms (Patient Health
      Questionnaire - Depression), and whether respondents had previously sought mental
      healthcare. RESULTS: Most participants fulfilled diagnostic criteria for a mood
      disorder (n = 181, 87.4%) and/or neurotic, stress-related and somatoform
      disorders (n = 120, 58.0%) according to the ICD-10. N = 94 (45.4%) participants
      had never received mental health treatment previously. Exploratory factor
      analysis of a list of 25 different causal explanations resulted in five factors:
      biomedical causes, person-related causes, childhood trauma, current stress and
      unhealthy behaviour. Attributing the present problem to biomedical causes, person
      related causes, childhood trauma and stress were all associated with stronger
      self-identification as having a mental illness. In persons who had never received
      mental health treatment previously, attribution to biomedical causes was related
      to greater perceived need and stronger help-seeking intentions. In those with
      treatment experience, lower attribution to person-related causes and stress were
      related to greater perceived need for professional help. CONCLUSIONS: While
      several causal explanations are associated with self-identification as having a
      mental illness, only biomedical attributions seem to be related to increase
      perceived need and help-seeking intentions, especially in individuals with no
      treatment experiences. Longitudinal studies investigating causal beliefs and help
      seeking are needed to find out how causal attributions guide help-seeking
      behaviour. From this study it seems possible that portraying professional mental
      health treatment as not being restricted to biomedical problems would contribute
      to closing the treatment gap for mental disorders.

PMID- 29335037
TI  - Is freedom (still) therapy? The 40th anniversary of the Italian mental health
      care reform.
AB  - On 13 May 1978, the Italian Parliament approved Law 180, universally known as
      'Basaglia Law' after the name of the leader of the anti-institutional movement
      which promoted this radical community mental health care reform. Forty years
      later, Italian psychiatry still runs a community care system, albeit with degrees
      of solidity and quality very varied along the peninsula. Mental health care is
      still an integral part of the National Health System, with liberal regulations on
      coercion and a lowest number of general hospital and residential facilities beds.
      Recently, Italy has also closed the special forensic psychiatric institutions and
      brought the care of the mentally ill offenders within the responsibilities of
      local Mental Health Departments. Over time, psychiatric deinstitutionalisation
      inspired policies in other sectors of Italian society, such as those regarding
      physical and intellectual disabilities, education of children with special needs,
      drug addictions and management of deviant minors. Furthermore, debate about Law
      180 has reached and maintained an international dimension, becoming a term of
      reference for international agencies such as the World Health Organization and
      the European Commission, for good and for evil. The overall balance sheet of the
      Reform process would seem mostly positive, though the last decade has seen many
      threats challenging the system. Mental health care services have been asked to do
      much more, in terms of care to a larger population with very diversified needs,
      but with much less resources, due to the financial consequences of the economic
      crisis. Although there is no evidence of a trend towards re-institutionalisation,
      intensity and quality of care may have fallen below acceptable standards in some
      parts of Italy.

PMID- 29335038
TI  - What is the prevalence of untreated depression and death ideation in older
      people? Data from the Irish Longitudinal Study on Aging.
AB  - : ABSTRACTObjective:Late life depression (LLD) confers significant morbidity and
      mortality but is well recognized that it often goes undetected or untreated. The
      objective of this study is to quantify the burden of untreated depression and
      death ideation (DI) at a population level. DESIGN: Cross-sectional study
      ascertaining the prevalence of, and factors associated with, untreated depression
      and DI. SETTING: This study, embedded within the Irish Longitudinal Study on
      Ageing, involves over 7,000 community-dwelling people aged >=50 years.
      MEASUREMENTS: Depression was defined as Centre for Epidemiological Studies
      Depression scale >=16 indicating current clinically relevant depressive symptoms
      or Composite International Diagnostic Interview indicative of major depressive
      episode within the last year. Participants not prescribed
      antidepressants/antipsychotics were defined as untreated. To define DI,
      participants were asked "In the last month, have you felt like you would rather
      be dead?" RESULTS: In total, 12% (839/7,055) met criteria for depression with 29%
      (241/839) on pharmacological therapy. Those with untreated depression were less
      likely to endorse symptoms of persistent low mood or worthlessness, but there was
      no difference in age or general practitioner (GP) visits compared to those on
      treatment. Over 3% (223/7,055) of participants had DI and less than one-third had
      visited their GP within the last year. CONCLUSIONS: This study demonstrates that
      two-thirds of depressed older people are not prescribed
      antidepressant/antipsychotic therapy. It is important to raise awareness of
      depression among older people and healthcare professionals, with particular focus
      on the fact that LLD is not an inevitable consequence of ageing and effective
      treatment is available.

PMID- 29335039
TI  - Replacing carbohydrate during a glucose challenge with the egg white portion or
      whole eggs protects against postprandial impairments in vascular endothelial
      function in prediabetic men by limiting increases in glycaemia and lipid
      peroxidation.
AB  - Eggs attenuate postprandial hyperglycaemia (PPH), which transiently impairs
      vascular endothelial function (VEF). We hypothesised that co-ingestion of a
      glucose challenge with egg-based meals would protect against glucose-induced
      impairments in VEF by attenuating PPH and oxidative stress. A randomised, cross
      over study was conducted in prediabetic men (n 20) who ingested isoenegertic
      meals (1674 kJ (400 kcal)) containing 100 g glucose (GLU), or 75 g glucose with
      1.5 whole eggs (EGG), seven egg whites (WHITE) or two egg yolks (YOLK). At 30 min
      intervals for 3 h, brachial artery flow-mediated dilation (FMD), plasma glucose,
      insulin, cholecystokinin (CCK), lipids (total, LDL- and HDL-cholesterol; TAG), F2
      isoprostanes normalised to arachidonic acid (F2-IsoPs/AA), and methylglyoxal were
      assessed. In GLU, FMD decreased at 30-60 min and returned to baseline levels by
      90 min. GLU-mediated decreases in FMD were attenuated at 30-60 min in EGG and
      WHITE. Compared with GLU, FMDAUC was higher in EGG and WHITE only. Relative to
      baseline, glucose increased at 30-120 min in GLU and YOLK but only at 30-90 min
      in EGG and WHITE. GlucoseAUC and insulinAUC were also lower in EGG and WHITE
      only. However, CCKAUC was higher in EGG and WHITE compared with GLU. Compared
      with GLU, F2-IsoPs/AAAUC was lower in EGG and WHITE but unaffected by YOLK.
      Postprandial lipids and methylglyoxal did not differ between treatments. Thus,
      replacing a portion of a glucose challenge with whole eggs or egg whites, but not
      yolks, limits postprandial impairments in VEF by attenuating increases in
      glycaemia and lipid peroxidation.

PMID- 29335040
TI  - Does a cognitive stress test predict progression from mild cognitive impairment
      to dementia equally well in clinical versus population-based settings?
AB  - : ABSTRACTBackground:Evidence suggests that semantic interference may be a
      sensitive indicator of early dementia. We examined the utility of the Semantic
      Interference Test (SIT), a cognitive stress memory paradigm which taps proactive
      and retroactive semantic interference, for predicting progression from mild
      cognitive impairment (MCI) to dementia in both a clinical and a population-based
      sample. METHODS: Participants with MCI in the clinical (n = 184) and population
      based (n = 435) samples were followed for up to four years. We employed receiver
      operating characteristic (ROC) methods to establish optimal thresholds for four
      different SIT indices. Threshold performance was compared in the two samples
      using logistic and Cox proportional hazard regression models. RESULTS: Within
      four years, 42 (22.8%) MCI individuals in the clinical sample and 45 (10.3%)
      individuals in the population-based sample progressed to dementia. Overall
      classification accuracy of SIT thresholds ranged from 61.4% to 84.8%. Different
      subtests of the SIT had slightly different performance characteristics in the two
      samples. However, regression models showed that thresholds established in the
      clinical sample performed similarly in the population sample before and after
      adjusting for demographics and other baseline neuropsychological test scores.
      CONCLUSIONS: Despite differences in demographic composition and progression
      rates, baseline SIT scores predicted progression from MCI to dementia similarly
      in both samples. Thresholds that best predicted progression were slightly below
      thresholds established for distinguishing between amnestic MCI and cognitively
      normal subjects in clinical practice. This confirms the utility of the SIT in
      both clinical and population-based samples and establishes thresholds most
      predictive of progression of individuals with MCI.

PMID- 29335042
TI  - Training and assessment in functional endoscopic sinus surgery.
AB  - BACKGROUND: Functional endoscopic sinus surgery is a common procedure performed
      within otolaryngology, but it carries potential for significant life-changing
      complications. It is therefore essential that trainees undergo adequate training.
      The European Working Time Directive has led to reduced operating time for the
      trainee surgeon. With variable access and the cost implications associated with
      cadaveric specimens, simulation can be an invaluable educational resource in
      surgical training. The current literature regarding the various simulation
      methodologies that have been used in functional endoscopic sinus surgery training
      is discussed. METHOD: A literature search was conducted using the key words
      'nasal', 'nasal polyps', 'endoscope', 'education and simulation', 'endoscopic
      sinus surgery' and 'training'. RESULTS: Twelve articles were identified; of
      these, eight trialled the use of simulators, two utilised ovine models and two
      used task trainers. CONCLUSION: Simulation has shown benefit in functional
      endoscopic sinus surgery training; however, a robust platform accessible to ENT
      trainees is lacking.

PMID- 29335041
TI  - Clinical correlates of resilience factors in geriatric depression.
AB  - BACKGROUND: Traditional perspectives conceptualize resilience as a trait and
      depression as resulting from resilience deficiency. However, research indicates
      that resilience varies substantially even among adults who are clinically
      depressed, as well as across the lifespan of an individual. Few studies have
      investigated resilience in depression, and even fewer have examined resilience in
      depressed older adults. METHODS: Three hundred thirty-seven adults >=60 years
      with major depressive disorder completed the Connor-Davidson Resilience Scale (CD
      RISC) and measures of mental health, quality of life (QOL), and medical
      comorbidity. Exploratory factor analysis was used to explore the factor structure
      of the CD-RISC. Correlations and general linear models were used to examine
      associations between resilience and other variables. RESULTS: The rotated
      component matrix indicated a four-factor model. Sorting of items by highest
      factor loading revealed constructs associated with (1) grit, (2) active coping
      self-efficacy, (3) accommodative coping self-efficacy, and (4) spirituality.
      Resilience was significantly correlated with increased age, lower cognitive
      functioning, greater cerebrovascular risk, and greater medical comorbidity.
      Resilience was negatively associated with mental health symptoms (depression,
      apathy, and anxiety) and positively associated with QOL. The final optimal model
      identified less depression, less apathy, greater medical comorbidity, higher QOL,
      and minority (non-White) race as factors that significantly explained variability
      in resilience. CONCLUSIONS: Resilience was significantly associated with a range
      of mental health constructs in a sample of older adults with depression. Future
      clinical trials and dismantling studies may help determine whether interventions
      targeting grit, active coping, accommodative coping, and spirituality can
      increase resilience and help prevent and treat depression in older adults.

PMID- 29335043
TI  - Stentless mirrored L-shaped septonasal flap versus stented flapless technique for
      endoscopic endonasal repair of bilateral congenital choanal atresia: a
      prospective randomised controlled study.
AB  - OBJECTIVES: To compare the outcomes of endoscopic repair of bilateral congenital
      choanal atresia using a flap technique without stenting versus endoscopic repair
      using stenting without a flap. METHODS: A prospective randomised controlled study
      was conducted, comprising 72 patients with bilateral congenital choanal atresia.
      The patients were randomised into two groups. Group A (42 patients) underwent
      endoscopic repair using a mirrored L-shaped flap without stenting, and group B
      (30 patients) underwent endoscopic repair using stenting without a flap. RESULTS:
      At a mean follow-up period of 18.2 months, endoscopic assessment revealed a
      patent posterior choana in 81 per cent and 83.33 per cent of patients in group A
      and group B respectively. Choanal stenosis occurred in 21.40 per cent and 33.33
      per cent of patients in group A and group B respectively. Granulation tissue was
      observed in 28.6 per cent and 53.3 per cent of patients in group A and group B
      respectively. CONCLUSION: The endoscopic approach utilising a flap without
      stenting is safe and effective, with a high success rate.

PMID- 29335044
TI  - Leges Sine Moribus Vanae.

PMID- 29335045
TI  - Letter to the Editor.

PMID- 29335047
TI  - Money in Tension with Ethics: A Commentary.
AB  - Monetary incentives are frequently in tension with evidence-based and cost
      effective clinical care, thus posing an ethical concern in the practice of
      dentistry. The purpose of this commentary was to examine the issue of treating
      children in the context of caries risk assessment and with specific reference to
      the periodic oral examination, radiographic surveillance, topical fluorides, and
      the pumice rubber prophylaxis.

PMID- 29335048
TI  - Antiplaque, Antifungal Effectiveness of Aloevera Among Intellectually Disabled
      Adolescents: Pilot Study.
AB  - PURPOSE: Various candida species have been associated with poor oral hygiene and
      active carious lesions. The purpose of this study was to evaluate the
      effectiveness of aloe vera compared to triclosan toothpaste against total
      candida, C. albicans, C. tropicalis, Candida krusei, and plaque/gingivitis among
      intellectually disabled adolescents over 30 days. METHODS: A double-blind
      prospective randomized trial was conducted among 40 intellectually disabled
      adolescents randomly allocated into aloe vera/triclosan groups. The gingival (Loe
      and Silness index), plaque (Silness and Loe index), and candidal carriage counts
      were assessed at baseline and follow-up. Caregivers brushed the participant's
      teeth twice a day using a modified bass method and refrained from any other oral
      hygiene practices for at least two hours prior to assessment. RESULTS: Aloe vera
      contaiing toothpaste caused significant reductions in gingival inflammation and
      plaque index scores compared to the triclosan group at the end of 30 days. Also,
      total candidal counts and C. albicans counts were significantly lower in the aloe
      vera group compared to triclosan at the end of the 30-day follow-up (P<0.05).
      CONCLUSION: Aloe vera-containing toothpaste was effective in reducing plaque,
      gingivitis, and overall candidal counts compared to triclosan. Moreover,
      individuals treated with aloe vera experienced improved oral health status
      without any negative side effects.

PMID- 29335049
TI  - Dental Treatment and Expenditures Under General Anesthesia Among Medicaid
      Enrolled Children in North Carolina.
AB  - PURPOSE: Many studies reporting dental utilization under general anesthesia (GA)
      are dated. The purpose of this study was to provide contemporaneous data about
      children receiving dental GA by: (1) determining trends in utilization and
      associated expenditures; and (2) examining the effects of provider distribution.
      METHODS: This time series cross-sectional study of Medicaid-eligible children
      ages zero to eight years old in North Carolina used aggregate Medicaid claims
      from State Fiscal Years (SFY) 2011 to 2015 to collect demographic and dental
      treatment information. Descriptive statistics were stratified by age and year to
      examine trends over time. Panel analysis techniques were used to explore regional
      effects of provider distribution on dental GA utilization. RESULTS: For SFY 2011
      to 2015, the overall dental utilization rate was 517.1 per 1,000 (total enrolled
      equals 632,941 children/year), and the dental GA utilization rate was 15.8 per
      1,000. Total dental expenditures averaged $113 million per year, and dental GA
      averaged $16.7 million per year. The dental GA proportion of expenditures
      increased over time (P<.001). Provider distribution did not affect dental GA
      utilization rate (P=.178) but did increase the number of children receiving
      dental GA (P<.001). CONCLUSIONS: Utilization and expenditures associated with
      dental treatment under general anesthesia continue to increase. While this
      reflects increased access to care, interventions should be examined to provide
      preventive care earlier in a child's life.

PMID- 29335050
TI  - Are Hypomineralized Primary Molars and Canines Associated with Molar-Incisor
      Hypomineralization?
AB  - PURPOSE: The purpose of this study was to evaluate the prevalence of and
      relationship between hypomineralized second primary molars (HSPM) and
      hypomineralized primary canines (HPC) with molar-incisor hypomineralization (MIH)
      in 1,963 schoolchildren. METHODS: The European Academy of Paediatric Dentistry
      (EAPD) criterion was used for scoring HSPM/HPC and MIH. Only children with four
      permanent first molars and eight incisors were considered in calculating MIH
      prevalence (n equals 858); for HSPM/HPC prevalence, only children with four
      primary second molars (n equals 1,590) and four primary canines (<small>n</small>
      equals 1,442) were considered. To evaluate the relationship between MIH/HSPM,
      only children meeting both criteria cited were considered (n equals 534), as was
      true of MIH/HPC (n equals 408) and HSPM/HPC (<small>n</small> equals 360; chi
      square test and logistic regression). RESULTS: The prevalence of MIH was 14.69
      percent (126 of 858 children). For HSPM and HPC, the prevalence was 6.48 percent
      (103 of 1,592) and 2.22 percent (32 of 1,442), respectively. A significant
      relationship was observed between MIH and both HSPM/HPC (P<0.001). The odds ratio
      for MIH based on HSPM was 6.31 (95 percent confidence interval [CI] equals 2.59
      to 15.13) and for HPC was 6.02 (95 percent CI equals 1.08 to 33.05). CONCLUSION:
      The results led to the conclusion that both hypomineralized second primary molars
      and hypomineralized primary canines are associated with molar-incisor
      hypomineralization, because children with HSPM/HPC are six times more likely to
      develop MIH.

PMID- 29335051
TI  - Effectiveness of a Preventive Recall Strategy for Children After Dental
      Rehabilitation with General Anesthesia.
AB  - PURPOSE: To test a more frequent preventive recall strategy following full-mouth
      dental rehabilitation (FMDR) in children with early childhood caries (ECC).
      METHODS: Patients were randomized into two groups: controls, who were scheduled
      to return at six-month intervals (6-MR); and the intervention group, who were
      scheduled to return at three-month intervals (3-MR and 6-MR). At baseline and at
      each recall, a caries risk assessment (CRA) and dental exam were completed.
      Analyses followed CONSORT recommendations, resulting in three analyses: intent-to
      treat; per-protocol; and an actual recall analysis. RESULTS: Intent-to-treat
      analysis showed no significant difference in CRA at six months (P>0.7); per
      protocol analysis showed borderline significance (P>.08); and actual recall
      analysis showed a statistically significant difference in CRA at six months
      (P=.021). For patients with both 3-MR and 6-MR, 44 percent were assessed at a
      high caries risk level; for patients with only a 6-MR, 72 percent were assessed
      as a high caries risk level (P=.021). No significant differences were found in
      caries incidence at six months. CONCLUSIONS: Following full-mouth dental
      rehabilitation, patients who returned for follow-ups at both three- and six-month
      intervals had a greater decrease in caries risk level compared to patients seen
      at six-month follow-up intervals.

PMID- 29335052
TI  - An Evaluation of Bite Pattern in Children with Severe-Early Childhood Caries
      Before and After Complete Dental Rehabilitation.
AB  - PURPOSE: The purpose of this study was to examine the changes in bite
      characteristics of children before and after the placement of multiple stainless
      steel crowns (SSCs) under general anesthesia (GA). METHODS: Twenty children
      scheduled for treatment under general anesthesia who needed SSCs in three or more
      posterior quadrants were included in this study. The bite was digitally analyzed
      and recorded preoperatively and at one and four weeks postoperatively. The
      occlusion time, number of force outliers, and distribution of force at each visit
      was recorded and compared. RESULTS: The placement of the SSCs in children
      significantly improved the bite characteristics of the participants. The
      placement of the SSC did not alter occlusion time, and there were no significant
      differences in occlusion time. While there was an increase in the number of
      outliers in the first week after the placement of the crown, there was a
      reduction in the total number of outliers at the end of one month. All the
      patients treated with bilateral placement of an SSC showed a posterior balanced
      occlusion post-operatively, a finding that was retained over the one-month follow
      up period. CONCLUSION: Bilateral placement of SSCs under general anesthesia does
      not significantly alter the occlusion of the child.

PMID- 29335053
TI  - Facial Nerve Paresis: Case Report of Blunt Facial Nerve Injury.
AB  - Facial nerve paresis is an uncommon but concerning condition in the pediatric
      population. The function and anatomy of the facial nerve is complex, and injuries
      to this structure may be associated with devastating physiological and
      psychological implications for the affected child and family. The purpose of this
      paper was to report a case involving a six-year-old Caucasian female who suffered
      a blunt traumatic injury to the orofacial region resulting in partial paralysis
      of the seventh cranial nerve. Following the injury, the child was unable to fully
      elevate the corner of her mouth. The deficit occurred immediately, and she
      experienced a prolonged course of recovery.

PMID- 29335054
TI  - Orbital, Mediastinal and Cervicofacial Subcutaneous Emphysema after Dental
      Rehabilitation in a Pediatric Patient.
AB  - Subcutaneous emphysema is a rare possible complication of dental procedures. The
      majority of the dental literature describes cases of localized areas of
      subcutaneous emphysema following various dental procedures, with a large number
      of these cases seen following intraoral surgical procedures. Classically,
      subcutaneous emphysema occurs within minutes to hours after conclusion of dental
      procedures and is commonly misdiagnosed as either an allergic reaction or acute
      post-operative swelling. This case report describes a four-year-old male who
      underwent dental rehabilitation for routine restorative dentistry without
      extractions under general anesthesia. He subsequently developed extensive
      subcutaneous emphysema involving the right periorbital region, cervicofacial
      spaces, and caudal extension to include the superior aspect of the mediastinum.
      The purpose of this report was to provide a brief review of the prior literature
      on the subject, report on the case, and review the management for patients with
      subcutaneous emphysema.

PMID- 29335056
TI  - Vegetable and Fruit Consumption among Chinese Adults and Associated Factors: A
      Nationally Representative Study of 170,847 Adults.
AB  - OBJECTIVE: This study examined vegetable and fruit (VF) consumption rate and its
      associated factors among Chinese adults. METHODS: Nationally representative data
      from the 2013 China Chronic Disease Surveillance survey were used. Dietary intake
      data, including VF consumption during the last 12 months, were collected. All
      analyses were weighted to obtain nationally representative estimates.
      Associations between VF consumption and other factors (e.g., meal frequency and
      physical activity) were examined through logistic regression analysis. RESULTS:
      The average fruit consumption was 102.3 g/day (95% CI: 97.0-107.6) and the
      average vegetable consumption was 350.6 g/day (95% CI: 339.3-361.8). Over half
      (53.2%, 95% CI: 50.9-55.4) of Chinese adults met the VF consumption of 400 g/day
      recommended by the World Health Organization (WHO). Rural residents had a higher
      prevalence of low VF consumption rate than urban residents [49.20% (95% CI: 46.2%
      52.2%) vs. 44.0% (95% CI: 41.7%-46.3%) P < 0.01]. Old age (OR = 1.01, 95% CI:
      1.00-1.01), low educational level, low income, minority ethnicity (OR = 1.41, 95%
      CI: 1.15-1.74), underweight (OR = 1.17, 95% CI: 1.03-1.33), single marital status
      (OR = 1.20, 95% CI: 1.08-1.33), low health literacy, irregular breakfast (OR =
      1.20, 95% CI: 1.04-1.38) or lunch (OR = 1.58, 95% CI: 1.26-1.99) habits, and no
      leisure-time physical activity were associated with low VF consumption.
      CONCLUSION: Only half of Chinese adults met the VF consumption recommended by the
      WHO. Low socio-economic status, irregular diet, and poor health literacy were
      likely associated with low VF consumption. National efforts and programs are
      needed to promote VF consumption.

PMID- 29335057
TI  - Study on the Simultaneously Quantitative Detection for beta-Lactoglobulin and
      Lactoferrin of Cow Milk by Using Protein Chip Technique.
AB  - OBJECTIVE: To research a protein chip method which can simultaneously
      quantitative detect beta-Lactoglobulin (beta-L) and Lactoferrin (Lf) at one time.
      METHODS: Protein chip printer was used to print both anti-beta-L antibodies and
      anti-Lf antibodies on each block of protein chip. And then an improved sandwich
      detection method was applied while the other two detecting antibodies for the two
      antigens were added in the block after they were mixed. The detection conditions
      of the quantitative detection for simultaneous measurement of beta-L and Lf with
      protein chip were optimized and evaluated. Based on these detected conditions,
      two standard curves of the two proteins were simultaneously established on one
      protein chip. Finally, the new detection method was evaluated by using the
      analysis of precision and accuracy. RESULTS: By comparison experiment, mouse
      monoclonal antibodies of the two antigens were chosen as the printing probe. The
      concentrations of beta-L and Lf probes were 0.5 mg/mL and 0.5 mg/mL,
      respectively, while the titers of detection antibodies both of beta-L and Lf were
      1:2,000. Intra- and inter-assay variability was between 4.88% and 38.33% for all
      tests. The regression coefficients of protein chip comparing with ELISA for beta
      L and Lf were better than 0.734, and both of the two regression coefficients were
      statistically significant (r = 0.734, t = 2.644, P = 0.038; and r = 0.774, t =
      2.998, P = 0.024). CONCLUSION: A protein chip method of simultaneously
      quantitative detection for beta-L and Lf has been established and this method is
      worthy in further application.

PMID- 29335058
TI  - Association of Dietary Pattern during Pregnancy and Gestational Diabetes
      Mellitus: A Prospective Cohort Study in Northern China.
AB  - OBJECTIVE: To examine the association of maternal dietary patterns during
      pregnancy with gestational diabetes mellitus (GDM) in northern China. METHODS:
      The dietary intakes of pregnant women were recorded twice by 24-hour dietary
      recalls for three days prior to having been diagnosed with GDM, at 5-15 and 24-28
      gestational weeks, respectively. GDM was diagnosed, and serum glycosylated
      hemoglobin (HbA1c) was measured at 24-28 weeks. Dietary patterns were assessed by
      factor analysis. The association of the dietary pattern with GDM and HbA1c was
      examined by multiple logistic models. RESULTS: Of 753 participants, 64 (8.5%)
      were diagnosed with GDM. Four dietary patterns were identified: Western pattern
      (dairy, baked/fried food and white meat), traditional pattern (light-colored
      vegetables, fine grain, red meat and tubers), mixed pattern (edible fungi,
      shrimp/shellfish and red meat) and prudent pattern (dark-colored vegetables and
      deep-sea fish). Compared with the prudent pattern, both the Western pattern and
      the traditional pattern were associated with an increased risk of GDM (aOR =
      4.40, 95% CI: 1.58-12.22; aOR = 4.88, 95% CI: 1.79-13.32) and a high level of
      HbA1c (aOR = 12.37, 95% CI: 1.47-103.91; aOR = 26.23, 95% CI: 2.54-270.74).
      Compared to the lowest quartile (Q), Q3 of the Western pattern scores and Q3-Q4
      of the traditional pattern scores were associated with a higher risk of GDM.
      CONCLUSION: The consumption of the Western pattern or the traditional pattern
      during pregnancy may increase the risk of GDM.

PMID- 29335059
TI  - Association of alpha2A-Adrenergic Receptor Genetic Variants with Platelet
      Reactivity in Chinese Patients on Dual Antiplatelet Therapy Undergoing
      Percutaneous Coronary Intervention.
AB  - OBJECTIVE: The alpha 2A-adrenergic receptor gene (ADRA2A) polymorphism in
      individuals modifies the antiplatelet response to sympathetic stimulation. The
      aim of this study was to investigate the effect of ADRA2A variants on platelet
      reactivity in Chinese patients on dual antiplatelet therapy (DAPT) after
      undergoing percutaneous coronary intervention (PCI). METHODS: From March 2011 to
      March 2013, 1,024 patients were enrolled in this prospective, single-center,
      observational study in China. Four single nucleotide polymorphisms (SNPs) of
      ADRA2A gene (rs11195419, rs3750625, rs13306146, and rs553668) and CYP2C19*2 were
      detected by ligase detection reaction (LDR), and adenosine diphosphate (ADP)
      inhibition was detected by thromboelastography (TEG(r)). RESULTS: The minor
      allele frequencies of ADRA2A SNPs were common. Platelet ADP inhibition was
      significantly different among patients carrying rs11195419 (adjusted P = 0.022)
      and rs3750625 (adjusted P = 0.016). The homozygous allele carriers had the lowest
      ADP inhibition. However, ADP inhibition was not significantly different in
      rs553668 and rs13306146. At the multivariate analysis, rs11195419 (P = 0.033),
      rs3750625 (P = 0.020) and CYP2C19*2 (P = 0.002) were independent predictors of
      ADP inhibition. Subgroups analysis based on sex showed rs11195419 (P = 0.003) and
      rs3750625 (P = 0.002) were significantly associated with ADP inhibition in males,
      but not in females. CONCLUSION: ADRA2A genetic variations were associated with
      ADP-induced platelet aggregation during DAPT in Chinese patients undergoing PCI,
      and the effect was particularly more pronounced in males.

PMID- 29335060
TI  - Characteristics of Long-term Nonprogressors and Viremia Controllers Infected with
      HIV-1 via Contaminated Blood Donations or Transfusions Conducted 20 Years
      Earlier.
AB  - To characterize long-term nonprogressors (LTNPs) and viremia controllers (VCs),
      infected with HIV-1 through contaminated blood donation or transfusion between
      1992 and 1996 in Henan, China. LTNPs and VCs were defined by CD4+T lymphocyte
      (CD4) count and viral load (VL). Of 29,294 patients infected with HIV-1 via
      contaminated blood donation or transfusion that had conducted for more than 20
      years, 92 were LTNPs/VCs. There were 70 LTNPs (0.24%), 43 VCs (0.15%), and 48
      LTNPs+VCs- (0.16%). VCs had a significantly lower CD4 nadir, compared to LTNPs
      and LTNPs+VCs-, and no significant differences for the highest VL and HIV-1 DNA.
      Cases P4 and P5 were LTNPs, while their VL reached approximately 4.3 log
      copies/mL. P6 was a VC, but with CD4 < 500 cells/MUL constantly. Data from the
      LTNPs/VCs cohort provided valuable information, future research is needed.

PMID- 29335061
TI  - Estimating HIV Incidence Rates among MSM in an Urban Area of Chongqing Using
      Three Approaches.
AB  - To evaluate the HIV pandemic in Chongqing, the pooled PCR, IgG-capture BED enzyme
      immunoassay (BED-CEIA), and cohort observations were used to estimate the HIV
      incidences among men who have sex with men (MSM). 617 MSM subjects completed the
      survey at a voluntary counseling and testing (VCT) site. The observed HIV
      incidence was 12.5 per 100 P-Ys (95% CI = 9.1-15.7). The annual acute HIV
      infection (AHI) incidence estimated by pooled PCR was 14.0% (95% CI = 10.9-17.1).
      The HIV-1 annual incidence estimated based on the BED-CEIA was 12.0% (95% CI =
      7.5-16.5). The HIV incidences estimated by these three approaches were consistent
      and complementary. The HIV incidence rates were alarmingly high with an uptrend
      among the urban MSM of Chongqing.

PMID- 29335062
TI  - Epidemiology of Measles Cases in South Darfur State, Sudan, 2011-2015.
AB  - Case-based surveillance measles data was defined according to World Health
      Organization (WHO) guidelines. A total of 511 measles cases were studied from
      2011 to 2015 in Southern Darfur State, Sudan and 58.1% of cases were confirmed
      from Nyala city. About 43.4% of cases were males, 56.6% of cases were female, and
      47.7% were children under five years old. Similarity, within February to June,
      the cases increased by 8.0% in children vaccinated through measles campaign, and
      5.3% in children that used child vaccination card and 78.7% in unvaccinated one.
      The epidemiologically linked (EPI-Linked) measles cases declined from 2011 to
      2015; consequently, Measles still remain to be a significant challenge in south
      Darfur state, Sudan.

PMID- 29335063
TI  - Tea Consumption is Associated with Increased Risk of Kidney Stones in Northern
      Chinese: A Cross-sectional Study.
AB  - Kidney stones are a common urinary system condition that can progress to kidney
      disease. Previous studies on the association between tea consumption and kidney
      stones are inconsistent. A cross-sectional study to investigate the association
      between tea consumption and kidney stones was conducted from 2013 to 2014 and
      recruited 9,078 northern Chinese adults. A total of 8,807 participants were
      included in the final analysis. Participants' prevalence of kidney stones was
      1.07%, 1.73%, and 2.25% based on their tea consumption frequency of never,
      occasionally, and often groups, respectively. Compared with the 'never' group,
      the odds ratios (95% confidence intervals) for the occurrence of kidney stones
      were 1.57 (1.00-2.46) and 1.65 (1.06-2.57) in the 'occasionally' and 'often'
      groups, respectively. After adjusting for sex, age, and other potential
      confounding factors, tea consumption still significantly increased the risk of
      kidney stones. Tea consumption is independently associated with an increased risk
      of kidney stones in the investigated population, suggesting that a decrease in
      the consumption of tea may be a preventive strategy for kidney stones.

PMID- 29335064
TI  - Real-time Assessment of Cytosolic, Mitochondrial, and Nuclear Calcium Levels
      Change in Rat Pheochromocytoma Cells during Pulsed Microwave Exposure Using a
      Genetically Encoded Calcium Indicator.
AB  - Little information is available about the effects of exposure to pulsed
      microwaves on neuronal Ca2+ signaling under non-thermal conditions. In this
      study, rat pheochromocytoma (PC12) cells were exposed to pulsed microwaves for 6
      min at a specific absorption rate (SAR) of 4 W/kg to assess possible real-time
      effects. During microwave exposure, free calcium dynamics in the cytosol,
      mitochondria, and nucleus of cells were monitored by time-lapse microfluorimetry
      using a genetically encoded calcium indicator (ratiometric-pericam, ratiometric
      pericam-mt, and ratiometric-pericam-nu). We established a waveguide-based real
      time microwave exposure system under accurately controlled environmental and
      dosimetric conditions and found no significant changes in the cytosolic,
      mitochondrial, or nuclear calcium levels in PC12 cells. These findings suggest
      that no dynamic changes occurred in [Ca2+]c, [Ca2+]m, or [Ca2+]n of PC12 cells at
      the non-thermal level.

PMID- 29335065
TI  - Effects of Maternal Marginal Iodine Deficiency on Interactions between Cerebellar
      Bergmann Glia Cells and Purkinje Cells in Rat Offspring.
AB  - Iodine deficiency (ID) during early pregnancy has an adverse effect on children's
      psychomotor and motor function but the mechanism has not been clarified.
      Therefore, our aim was to study the effect of maternal marginal ID on cerebellar
      neurodevelopment and the underlying mechanism. After obtaining marginal ID rats,
      we examined interactions between Bergmann glia cells (BGs) and Purkinje cells
      (PCs) using immunofluorescence and expression of the glutamate transporter and
      receptor by western blot. Our results showed that marginal ID reduced the number
      of contacted points between BGs and PCs, and disturbed expression of the
      glutamate transporter and receptor. Our results support the hypothesis that
      marginal ID inhibits interactions of BGs-PCs, which may be involved in abnormal
      regulation of the glutamate transporter and receptor.

PMID- 29335066
TI  - Up- and Down-regulated Leukemia-related Protein 16 Affects ERalpha Expression and
      Prolactin Secretion by GH3 Cells.
AB  - Prolactinoma is an estrogen-related tumor and leukemia-related protein 16 (LRP16)
      is correlated with the progression of estrogen-related tumors, but the regulatory
      mechanism between LRP16 and prolactinoma remain unclear. This study demonstrates
      a variation in LRP16 with estrogen receptor alpha (ERalpha) in prolactinoma
      models and the up and downregulation effects of LRP16 on prolactin secretion of
      pituitary adenomas cells (GH3 cells). In our study, 50 male SD rats (30-day-old)
      were randomly divided into five groups of 10 rats each. After 120 days of
      treatment, the rats were sacrificed, and the expression of LRP16 and ERalpha were
      examined by Western blot and immunohistochemistry to explore the changes in
      ERalpha, LRP16, and prolactin. After siRNA transfection of the respective genes,
      the GH3 cells were cultured, and their secretory function as well as the
      expression of ERalpha mRNA and prolactin were analyzed by enzyme-linked
      immunosorbent assay and real-time-polymerase chain reaction analysis. The results
      show that secretion of prolactin by GH3 cells can be affected by up and
      downregulating LRP16 expression, which may provide a novel medical therapy in
      clinical trials.

PMID- 29335067
TI  - Gata6 in pluripotent stem cells enhance the potential to differentiate into
      cardiomyocytes.
AB  - Pluripotent stem cell (PSC) variations can cause significant differences in the
      efficiency of cardiac differentiation. This process is unpredictable, as there is
      not an adequate indicator at the undifferentiated stage of the PSCs. We compared
      global gene expression profiles of two PSCs showing significant differences in
      cardiac differentiation potential. We identified 12 up-regulated genes related to
      heart development, and we found that 4 genes interacted with multiple genes.
      Among these genes, Gata6 is the only gene that was significantly induced at the
      early stage of differentiation of PSCs to cardiomyocytes. Gata6 knock-down in
      PSCs decreased the efficiency of cardiomyocyte production. In addition, we
      analyzed 6 mESC lines and 3 iPSC lines and confirmed that a positive correlation
      exists between Gata6 levels and efficiency of differentiation into
      cardiomyocytes. In conclusion, Gata6 could be utilized as a biomarker to select
      the best PSC lines to produce PSC-derived cardiomyocytes for therapeutic
      purposes. [BMB Reports 2018; 51(2): 85-91].

PMID- 29335068
TI  - Imprinted gene Zinc finger protein 127 is a novel regulator of master
      pluripotency transcription factor, Oct4.
AB  - Induced pluripotent stem cells (iPSCs) show great promise for replacing current
      stem cell therapies in the field of regenerative medicine. However, the original
      method for cellular reprogramming, involving four exogenous transcription
      factors, is characterized by low efficiency. Here, we focused on using epigenetic
      modifications to enhance the reprogramming efficiency. We hypothesized that there
      would be a new reprogramming factor involved in DNA demethylation, acting on the
      promoters of pluripotency-related genes. We screened proteins that bind to the
      methylated promoter of Oct4 and identified Zinc finger protein 127 (Zfp127), the
      functions of which have not yet been identified. We found that Zfp127 binds to
      the Oct4 promoter. Overexpression of Zfp127 in fibroblasts induced demethylation
      of the Oct4 promoter, thus enhancing Oct4 promoter activity and gene expression.
      These results demonstrate that Zfp127 is a novel regulator of Oct4, and may
      become a potent target to improve cellular reprogramming. [BMB Reports 2018;
      51(5): 242-248].

PMID- 29335069
TI  - Functional roles of glutamic acid E143 and E705 residues in the N-terminus and
      transmembrane domain 7 of Anoctamin 1 in calcium and noxious heat sensing.
AB  - Anoctamin 1 (ANO1) is an anion channel that is activated by changes in cytosolic
      Ca2+ concentration and noxious heat. Although the critical roles of ANO1 have
      been elucidated in various cell types, the control of its gating mechanisms by
      Ca2+ and heat remain more elusive. To investigate critical amino acid residues
      for modulation of Ca2+ and heat sensing, we constructed a randomized mutant
      library for ANO1. Among 695 random mutants, reduced Ca2+ sensitivity was observed
      in two mutants (mutant 84 and 87). Consequently, the E143A mutant showed reduced
      sensitivity to Ca2+ but not to high temperatures, whereas the E705V mutant
      exhibited reduced sensitivity to both Ca2+ and noxious heat. These results
      suggest that the glutamic acids (E) at 143 and 705 residues in ANO1 are critical
      for modulation of Ca2+ and/or heat responses. Furthermore, these findings help to
      provide a better understanding of the Ca2+-mediated activation and heat-sensing
      mechanism of ANO1. [BMB Reports 2018; 51(5): 236-241].

PMID- 29335070
TI  - Cell proliferation and migration mechanism of caffeoylserotonin and serotonin via
      serotonin 2B receptor in human keratinocyte HaCaT cells.
AB  - Caffeoylserotonin (CaS), one derivative of serotonin (5-HT), is a secondary
      metabolite produced in pepper fruits with strong antioxidant activities. In this
      study, we investigated the effect of CaS on proliferation and migration of human
      keratinocyte HaCaT cells compared to that of 5-HT. CaS enhanced keratinocyte
      proliferation even under serum deficient condition. This effect of CaS was
      mediated by serotonin 2B receptor (5-HT2BR) related to the cell proliferation
      effect of 5-HT. We also confirmed that both CaS and 5-HT induced G1 progression
      via 5-HT2BR/ERK pathway in HaCaT cells. However, Akt pathway was additionally
      involved in upregulated expression levels of cyclin D1 and cyclin E induced by
      CaS by activating 5-HT2BR. Moreover, CaS and 5-HT induced cell migration in HaCaT
      cells via 5-HT2BR. However, 5-HT regulated cell migration only through ERK/AP
      1/MMP9 pathway while additional Akt/NF-kappaB/MMP9 pathway was involved in the
      cell migration effect of CaS. These results suggest that CaS can enhance
      keratinocyte proliferation and migration. It might have potential as a reagent
      beneficial for wound closing and cell regeneration. [BMB Reports 2018; 51(4): 188
      193].

PMID- 29335072
TI  - Rebound excitability mediates motor abnormalities in Parkinson's disease.
AB  - Parkinson's disease (PD) is a debilitating disorder resulting from loss of
      dopamine neurons. In dopamine deficient state, the basal ganglia increases
      inhibitory synaptic outputs to the thalamus. This increased inhibition by the
      basal ganglia output is known to reduce firing rate of thalamic neurons that
      relay motor signals to the motor cortex. This 'rate model' suggests that the
      reduced excitability of thalamic neurons is the key for inducing motor
      abnormalities in PD patients. We reveal that in response to inhibition, thalamic
      neurons generate rebound firing at the end of inhibition. This rebound firing
      increases motor cortical activity and induces muscular responses that triggers
      Parkinsonian motor dysfunction. Genetic and optogenetic intervention of the
      rebound firing prevent motor dysfunction in a mouse model of PD. Our results
      suggest that inhibitory synaptic mechanism mediates motor dysfunction by
      generating rebound excitability in the thalamocortical pathway. [BMB Reports
      2018; 51(1): 3-4].

PMID- 29335071
TI  - Adequate concentration of B cell leukemia/lymphoma 3 (Bcl3) is required for
      pluripotency and self-renewal of mouse embryonic stem cells via downregulation of
      Nanog transcription.
AB  - B cell leukemia/lymphoma 3 (Bcl3) plays a pivotal role in immune homeostasis,
      cellular proliferation, and cell survival, as a co-activator or co-repressor of
      transcription of the NF-kappaB family. Recently, it was reported that Bcl3
      positively regulates pluripotency genes, including Oct4, in mouse embryonic stem
      cells (mESCs). However, the role of Bcl3 in the maintenance of pluripotency and
      self-renewal activity is not fully established. Here, we report the dynamic
      regulation of the proliferation, pluripotency, and self-renewal of mESCs by Bcl3
      via an influence on Nanog transcriptional activity. Bcl3 expression is
      predominantly observed in immature mESCs, but significantly decreased during cell
      differentiation by LIF depletion and in mESC-derived EBs. Importantly, the
      knockdown of Bcl3 resulted in the loss of self-renewal ability and decreased cell
      proliferation. Similarly, the ectopic expression of Bcl3 also resulted in a
      significant reduction of proliferation, and the self-renewal of mESCs was
      demonstrated by alkaline phosphatase staining and clonogenic single cell-derived
      colony assay. We further examined that Bcl3-mediated regulation of Nanog
      transcriptional activity in mESCs, which indicated that Bcl3 acts as a
      transcriptional repressor of Nanog expression in mESCs. In conclusion, we
      demonstrated that a sufficient concentration of Bcl3 in mESCs plays a critical
      role in the maintenance of pluripotency and the self-renewal of mESCs via the
      regulation of Nanog transcriptional activity. [BMB Reports 2018; 51(2): 92-97].

PMID- 29335073
TI  - [Enhance research, prevention and control of pertussis for protecting public
      confidence in vaccination: focus on the adverse events of vaccine with
      insufficient potency and its long-term impacts].
AB  - On November 3, 2017, the China Food and Drug Administration reported that the
      potency indexes of two batches of diphtheria-pertussis-tetanus vaccines produced
      by two companies did not reach the requirements. Insufficient potency could
      affect the protection effect of these vaccines immunization. Currently, pertussis
      cases have already showed an increasing trend in China and could last for several
      years. Such an increase could be linked to these adverse events of vaccine with
      insufficient potency, which could become an evidence to challenge or deny the
      effectiveness of vaccination, and brings a persistent inhibition of the public's
      acceptance for vaccination. The wider global context of pertussis resurgence,
      previous underestimate on the domestic pertussis, the promotion of detection
      methods, the change of knowledge about pertussis, the confirmation of pertussis
      in elder children and adults, the antigenicity variation of pertussis strains
      could lead to a significant increase of pertussis cases. Health researchers and
      clinical workers should raise awareness about these factors, and assess
      rationally the impact of vaccine titer deficiency on pertussis epidemiology for
      maintaining and promoting public confidence in vaccination.

PMID- 29335074
TI  - Trends in narcotics and sedative use during mechanical ventilation of preterm
      infants in Canadian neonatal intensive care units.
AB  - OBJECTIVE: Mechanical ventilation (MV) in preterm infants (PTI) causes
      discomfort. Whether it causes pain is controversial. Meta analysis reviews of
      published work on PTI during MV have shown no clinically significant impact of
      opioids on pain scales, and hence not recommended for routine use in neonatal
      intensive care units (NICUs). Similarly regular use of sedative midazolam is also
      not recommended. Therefore we hypothesized a downward trend in narcotics and
      sedatives used in MV of PTI in NICUs. This study aimed to assess trends of
      sedatives and narcotics use during MV of PTI in Canadian NICUs during 2004-2009.
      METHODS: PTI born at gestational age (GA) of <35 weeks requiring invasive MV for
      >24 hours were identified retrospectively from the Canadian Neonatal Network
      database for 2004-2009. PTI were excluded if moribund on admission, had major
      congenital anomalies, surgery (except laser eye surgery), necrotizing
      enterocolitis, chest tube or history of maternal narcotic abuse. PTI were
      classified according to whether they received any narcotics (morphine, fentanyl,
      methadone, sufentanyl, meperidine, alfentynl and codiene) or sedatives (chloral
      hydrate, midazolam, lorazepam, phenobarbital, pentobarbital, ketamine and
      propofol) for >24 consecutive hours during MV. Trends of narcotics and sedatives
      were assessed using the Cochrane-Armitage Trend test separately for PTI born at
      <29 and 29-34 weeks of GA. RESULTS: Among 5 638 study subjects, 2 169 (38.5%)
      received narcotics and 897 (15.9%) received sedatives. The most common narcotics
      were morphine (62.2%) and fentanyl (63.8%) and sedatives were phenobarbital
      (44.9%) and chloral hydrate (44.2%). A significant decreasing trend (P<0.01) in
      the use of any sedatives during MV was observed in PTI <29 and 29-34 weeks of GA.
      However, the use of any narcotics during MV increased significantly (P=0.03)
      among PTI <29 weeks of GA, and no change in trend was detected for PTI born at 29
      34 weeks of GA. CONCLUSIONS: The use of sedatives during MV in PTI born at <35
      weeks of GA was positively affected, however the narcotics use during MV remained
      constant for PTI born at 29-34 weeks, and increased in extremely low GA group
      (less than 29 weeks) suggesting evidence based practice change was not observed
      during the study period.

PMID- 29335075
TI  - [A study of Ververck index in 16 865 singleton neonates with a gestational age of
      27-42 weeks in Shenzhen, China].
AB  - OBJECTIVE: Ververck index (VI) reflects thoracic development, body type, and
      nutritional status. This study aimed to investigate the VI of singleton neonates
      with a gestational age (GA) of 27-42 weeks at birth, and to establish percentile
      curves of VI of the neonates. METHODS: Cross-sectional cluster sampling was
      performed between April 2013 and September 2015. Body weight, body length, and
      chest circumference were measured for 16 865 singleton neonates with a GA of 27
      42 weeks in two hospitals in Shenzhen, China. VI was calculated and the
      percentile curves of VI were plotted for the neonates. RESULTS: Mean VIs were
      obtained for singleton neonates with a gestational age of 27-42 weeks (in three
      groups of male, female, and both sexes), and related 3rd-97th percentile curves
      were plotted. As for the 50th percentile curve, the singleton neonates with a GA
      of 27 weeks had the lowest 50th percentile value of VI, which gradually increased
      with the increase in GA. The singleton neonates with a GA of 42 weeks had the
      highest 50th percentile value of VI. Girls had a slightly higher 50th percentile
      value of VI than boys in all GA groups. CONCLUSIONS: VI of neonates increases
      with the increase in GA. Female neonates may have a slightly better thoracic
      development, body type, and nutritional status than male neonates at birth. The
      percentile curves of VI plotted for singleton neonates with a GA of 27-42 weeks
      (in three groups of male, female, and both sexes) can provide a basis for
      evaluating thoracic development, body type, and nutritional status of neonates at
      birth in Shenzhen, China.

PMID- 29335076
TI  - [Value of arterial blood lactic acid in the evaluation of disease severity and
      prognosis in neonatal shock].
AB  - OBJECTIVE: To evaluate the value of blood lactic acid (BLA) as a predictor for
      the severity and prognosis of neonatal shock. METHODS: A total of 326 neonates
      with shock were enrolled and divided into three groups based on the severity,
      namely mild group (n=147), moderate group (n=105), and severe group (n=74). BLA
      level was measured during and early after (about 6 hours later) fluid
      resuscitation, and lactate clearance rate (LCR) was calculated. The receiver
      operating characteristic (ROC) curve was applied to evaluate the predictive value
      of BLA in neonatal shock. RESULTS: BLA level was high in all subjects prior to
      treatment, and was highest in the severe group and lowest in the mild group
      (P<0.01). BLA level was significantly higher among patients with septic shock
      than among those with hypovolemic, cardiogenic, and asphyxiating shock (P<0.05).
      BLA level was significantly reduced in patients in recovery after treatment
      (P<0.05). Mortality was significantly lower in patients with BLA level <=4 mmol/L
      or LCR >=10% than in those with BLA level >4 mmol/L or LCR <10% (P<0.01). BLA at
      11.15 mmol/L had 100% sensitivity and 96.8% specificity in predicting severe
      shock. BLA at 10.65 mmol/L had 88.9% sensitivity and 74.1% specificity in
      predicting the prognosis (survival or dead) of newborns with shock. CONCLUSIONS:
      In neonates with shock, arterial BLA level increases as the disease severity
      increases and is associated with prognosis, so it is a useful predictor of the
      severity and prognosis of neonatal shock.

PMID- 29335077
TI  - [Burden of pediatric cancer in Jiangxi, China, in 2010 and 2015].
AB  - OBJECTIVE: To study the burden of pediatric cancer in Jiangxi, China, in 2010 and
      2015 and its changes from 2010 to 2015. METHODS: The data of pediatric cancer in
      Jiangxi in 2010 and 2015 were collected from the Global Burden of Disease Study
      2015 in China, including number of cases, number of deaths, years of life lost
      (YLL), years lived with disability (YLD), and disability-adjusted life years
      (DALY). The standardized incidence rate, mortality rate, and DALY rate were
      calculated with the national census data in 2010 as the standard population, in
      order to evaluate the changes in incidence, mortality, and disease burden of
      pediatric cancer in Jiangxi. RESULTS: In both 2010 and 2015, boys had higher
      numbers of cases, deaths, and DALY than girls, and the 5-14 years group had
      higher numbers than the 0-4 years group; boys had higher incidence rate,
      mortality rate, and DALY rate than girls, and the 0-4 years group had higher
      rates than the 5-14 years group. In 2015, the standardized incidence rate of
      pediatric cancer was reduced by 6.66% in the 0-4 years group and 17.56% in the 5
      14 years group; the standardized mortality rate was reduced by 11.34% in the 0-4
      years group and 21.78% in the 5-14 years group; the standardized DALY rate was
      reduced by 11.27% in the 0-4 years group and 21.67% in the 5-14 years group.
      Among the different types of pediatric cancer, leukemia had the highest
      standardized DALY rate in 2010 and 2015, followed by brain cancer and non
      Hodgkin's lymphoma. CONCLUSIONS: There was a certain reduction in the burden of
      pediatric cancer in Jiangxi from 2010 to 2015. Leukemia, brain cancer, and non
      Hodgkin's lymphoma are the focus of prevention and treatment, and children aged
      less than 5 years and boys should be closely monitored.

PMID- 29335078
TI  - [Value of indoleamine 2,3-dioxygenase in diagnosis of systemic inflammatory
      response syndrome after cardiopulmonary bypass in children with congenital heart
      disease].
AB  - OBJECTIVE: To study the value of indoleamine 2,3-dioxygenase (IDO) in the early
      diagnosis of systemic inflammatory response syndrome (SIRS) after cardiopulmonary
      bypass in children with congenital heart disease. METHODS: A total of 90 children
      with congenital heart disease who underwent cardiopumonary bypass surgery between
      May 2012 and January 2016 were enrolled. According to the prsence or absence of
      SIRS after surgery, they were divided into SIRS group (n=43) and control group
      (n=47). Peripheral blood samples were collected before surgery, during surgery,
      and after surgery. Serum levels of IDO, C-reactive protein (CRP), and interleukin
      6 (IL-6) were measured and compared between the two groups. The receiver
      operating characteristic (ROC) curve was used to evaluate their diagnostic
      efficiency. RESULTS: Compared with the control group, the SIRS group had higher
      serum CRP levels at 72 hours after surgery, higher IL-6 levels during surgery and
      at 72 hours after surgery, and higher IDO levels at 24 and 72 hours after
      surgery. IDO had a certain value in the diagnosis of SIRS at 24 hours after
      surgery with an area under the ROC curve (AUC) of 0.793, a specificity of 100%,
      and a sensitivity of 58.14%. CRP, IL-6, and IDO had a certain value in the
      diagnosis of SIRS at 72 hours after surgery. IDO had the highest diagnostic
      efficiency with an AUC of 0.927, a specificity of 95.74%, and a sensitivity of
      76.74% at 72 hours after surgery. CONCLUSIONS: IL-6, CRP, and IDO have a certain
      value in the diagnosis of SIRS after surgery for congenital heart disease, and
      IDO has a higher diagnostic efficiency. IDO can predict the development of SIRS
      in children after surgery for congenital heart disease earlier.

PMID- 29335079
TI  - [Expression of plasma miRNA-497 in children with sepsis-induced myocardial injury
      and its clinical significance].
AB  - OBJECTIVE: To study the expression of plasma miRNA-497 in children with sepsis
      induced myocardial injury and its clinical significance. METHODS: A total of 148
      children with sepsis were enrolled. According to the presence or absence of
      myocardial injury, these children were divided into myocardial injury group
      (n=58) and non-myocardial injury group (n=90). The two groups were compared in
      terms of the changes in plasma levels of miRNA-497, cardiac troponin I (cTnI),
      creatine kinase-MB (CK-MB), N-terminal pro-brain natriuretic peptide (NT-proBNP),
      procalcitonin (PCT), and C-reactive protein (CRP) and left ventricular ejection
      fraction (LVEF). The receiver operating characteristic (ROC) curve was plotted to
      evaluate the value of plasma miRNA-497, cTnI, and CK-MB in the diagnosis of
      myocardial injury. A Pearson correlation analysis was used to determine the
      correlation of miRNA-497 with cTnI, CK-MB, NT-proBNP, PCT, CRP, and LVEF.
      RESULTS: Compared with the non-myocardial injury group, the myocardial injury
      group had significantly higher plasma levels of miRNA-497, cTnI, CK-MB, NT
      proBNP, PCT, and CRP (P<0.05). Plasma miRNA-497, cTnI, and CK-MB when measured
      alone or in combination had an area under the ROC curve of 0.918, 0.931, 0.775,
      and 0.940 respectively. At the optimal cut-off value of 2.05, miRNA-497 had a
      sensitivity of 90.4% and a specificity of 91.2%. The correlation analysis showed
      that there was a good correlation between plasma miRNA-497 and cTnI in children
      with myocardial injury (r=0.728, P<0.01). CONCLUSIONS: Plasma miRNA-497 has a
      similar value as cTnI in the diagnosis of sepsis-induced myocardial injury in
      children and may be used as a potential marker for early diagnosis of myocardial
      injury.

PMID- 29335080
TI  - [Clinical characteristics of refractory Mycoplasma pneumoniae pneumonia in
      children].
AB  - OBJECTIVE: To provide a basis for early diagnosis and treatment of refractory
      Mycoplasma pneumoniae pneumonia (RMPP) in children by comparing the clinical
      characteristics of RMPP and general Mycoplasma pneumoniae pneumonia (MPP).
      METHODS: Children with MPP hospitalized between October 2015 and December 2016
      were selected as study subjects. According to the diagnostic criteria, children
      were divided into RMPP group (n=152) and MPP group (n=551). The differences
      between the two groups in the basic situation, clinical manifestations, infection
      parameters and myocardial enzymes were compared. RESULTS: There were no
      significant differences in gender and age between the RMPP and MPP groups
      (P>0.05). The peak temperature in the RMPP group was significantly higher than
      that in the MPP group on the first day of admission (P<0.01). The percentage of
      children with augmentation in the RMPP group was lower than that in the MPP group
      (P=0.009). The percentage of neutrophils [Ne(%)] and serum procalcitonin (PCT)
      levels in the RMPP group were both higher than those in the MPP group (P<0.05),
      while the percentage of lymphocytes was significantly lower in the RMPP group
      (P<0.05). The serum levels of aspartate aminotransferase (AST) and lactate
      dehydrogenase (LDH) in the RMPP group were also higher than those in the MPP
      group (P<0.05). Binary logistic regression analysis showed that the peak
      temperature and LDH were closely related to RMPP in children (P<0.05). Receiver
      operating characteristic (ROC) curve analysis showed that the area under the
      curve (AUC) of the peak temperature and LDH for the diagnosis of RMPP was 0.647
      and 0.637 respectively. In children <=2 years old, when the threshold value of
      LDH was 400 U/L, the diagnostic sensitivity was 52.63% and the specificity was
      54.84%. In children above 2 years old, when the threshold value of LDH was 335
      U/L, the diagnostic sensitivity was 69.92% and the specificity was 51.55%.
      CONCLUSIONS: The children with RMPP have a high fever in the early stage.
      Meanwhile there are abnormal laboratory test results in these children. Elevated
      serum LDH levels have a high clinical value of early diagnosis of RMPP,
      especially in children above 2 years.

PMID- 29335081
TI  - [Expression of vascular intercellular adhesion molecule-1 and its significance in
      children with bronchiolitis].
AB  - OBJECTIVE: To investigate the expression of intercellular adhesion molecule-1
      (ICAM-1) in serum and induced sputum supernatant in children with bronchiolitis,
      as well as its role in the pathogenesis of bronchiolitis in children. METHODS: A
      total of 67 children with bronchiolitis who were diagnosed and hospitalized
      between July 2015 and January 2017 were enrolled. According to the diagnostic
      criteria, these children were divided into mild group with 22 children, moderate
      group with 24 children, and severe group with 21 children. A total of 20 children
      who underwent physical examination were enrolled as healthy control group. ELISA
      was used to measure the level of ICAM-1 in serum and induced sputum supernatant
      in the children with bronchiolitis in the acute stage and recovery stage and the
      children in the healthy control group. RESULTS: Compared with the healthy control
      group, the mild, moderate, and severe bronchiolitis groups had a significant
      increase in the level of ICAM-1 in serum and sputum (P<0.01). Compared with the
      mild group, the moderate and severe groups had a significant increase in the
      level of ICAM-1 in serum and sputum (P<0.01). Compared with the moderate group,
      the severe group had a significant increase in the level of ICAM-1 in serum and
      sputum (P<0.01). Compared with the children with bronchiolitis in the acute
      stage, the children in the recovery stage had a significant reduction in the
      level of ICAM-1 in serum and sputum (P<0.01). The correlation analysis showed
      that in the acute stage, the level of ICAM-1 in serum was positively correlated
      with that in sputum in children with bronchiolitis (r=0.875, P<0.001).
      CONCLUSIONS: ICAM-1 is involved in the pathogenesis of bronchiolitis and is
      associated with disease severity.

PMID- 29335082
TI  - [A comparative analysis of anti-N-methyl-D-aspartate receptor encephalitis with
      or without abnormal findings on cranial magnetic resonance imaging].
AB  - OBJECTIVE: To investigate the clinical features of children with anti-N-methyl-D
      aspartate receptor (anti-NMDAR) encephalitis with normal or abnormal cranial
      magnetic resonance imaging (MRI) findings via a comparative analysis. METHODS: A
      retrospective analysis was performed for the clinical data of 33 children with
      anti-NMDAR encephalitis. The clinical features and prognosis were compared
      between the children with normal and abnormal cranial MRI findings. RESULTS: In
      the 33 children with anti-NMDAR encephalitis, the most common initial symptoms
      were seizures (61%) and involuntary movement (61%), followed by language disorder
      (54%), mental and behavioral abnormalities (52%), and disturbance of
      consciousness (30%). All children had positive anti-NMDAR antibody in the
      cerebrospinal fluid, and 29 children (88%) had positive serum antibody. Of all
      the children, 15 (46%) had increased leukocytes in the cerebrospinal fluid, 3
      (9%) had an increase in protein, and 29 (88%) had positive oligoclonal band; 26
      children (79%) had electroencephalographic abnormalities (epileptic wave, slow
      wave, or a combination of these two types of waves). One child experienced
      respiratory failure. One child was found to have germinoma in the sellar region
      during follow-up. Of all the 33 children, 13 (39%) had abnormal cranial MRI
      findings, with hypointensity or isointensity on T1W1 and hyperintensity on T2WI
      and T2-FLAIR; 2 children had dural enhancement. As for the location of lesion, 5
      children (38%) had lesions in the temporal lobe, 3 (23%) in the frontal lobe, 3
      (23%) in the basal ganglia, 2 (15%) in the parietal lobe, 2 (15%) in the
      occipital lobe, 2 (15%) in the brainstem, 1 (8%) in the thalamus, and 1 (8%) in
      the cerebellum. Among the 13 children with abnormal cranial MRI findings, 5 (38%)
      had lesions mainly in the grey matter and 8 (62%) had lesions mainly in the white
      matter. Compared with the children with normal cranial MRI findings, the children
      with abnormal cranial MRI findings had significantly higher proportion of
      children with prodromal infection, incidence rate of disturbance of
      consciousness, probability of recurrence, Glasgow score, incidence rate of
      increased leukocytes in the cerebrospinal fluid, and application rate of second
      line treatment (P<0.05). CONCLUSIONS: Children with anti-NMDAR encephalitis and
      abnormal cranial MRI findings have certain clinical features, which may provide
      guidance for the evaluation of disease conditions and the selection of diagnostic
      and treatment measures.

PMID- 29335083
TI  - [Clinical and cytogenetic study in a child with de novo chromosome 9
      abnormality].
AB  - This study aimed to analyze the clinical phenotype of chromosome 9p deletion or
      duplication and its relationship with karyotype. A patient, female, aged 6
      months, visited the hospital due to motor developmental delay. Karyotype analysis
      identified abnormalities of chromosome 9 short arm, and high-throughput
      sequencing found 9p24.3-9p23 deletion and 9p23-9p13.1 duplication. Her parents
      had a normal karyotype. Karyotype analysis combined with high-throughput
      sequencing is of great significance for improving the efficiency of etiological
      diagnosis in children with motor developmental delay or multiple congenital
      deformities and mental retardation.

PMID- 29335084
TI  - [Influence of cow's milk protein allergy on the diagnosis of functional
      gastrointestinal diseases based on the Rome IV standard in infants and young
      children].
AB  - OBJECTIVE: To study the influence of cow's milk protein allergy (CMPA) on the
      diagnosis of functional gastrointestinal diseases (FGID) based on the Rome IV
      standard in infants and young children. METHODS: A total of 84 children aged 1
      month to 3 years who were diagnosed with CMPA were enrolled as the case group,
      and 84 infants and young children who underwent physical examination and had no
      CMPA were enrolled as the control group. The pediatricians specializing in
      gastroenterology asked parents using a questionnaire for the diagnosis of FGID
      based on the Rome IV standard to assess clinical symptoms and to diagnose FGID.
      RESULTS: The case group had a significantly higher incidence rate of a family
      history of allergies than the control group (P<0.05). In the case group, 38 (45%)
      met the Rome IV standard for the diagnosis of FGID, while in the control group,
      13 (15%) met this standard (P<0.05). According to the Rome IV standard for FGID,
      the case group had significantly higher diagnostic rates of reflex, functional
      diarrhea, difficult defecation, and functional constipation than the control
      group (P<0.05). The children who were diagnosed with FIGD in the control group
      were given conventional treatment, and those in the case group were asked to
      avoid the intake of cow's milk protein in addition to the conventional treatment.
      After 3 months of treatment, the case group had a significantly higher response
      rate to the treatment than the control group (P<0.05). CONCLUSIONS: In infants
      and young children, CMPA has great influence on the diagnosis of FGID based on
      the Rome IV standard. The possibility of CMPA should be considered during the
      diagnosis of FGID.

PMID- 29335085
TI  - [Impact of transition readiness on quality of life in children with chronic
      diseases].
AB  - OBJECTIVE: To investigate the current quality of life in children with chronic
      diseases, and to explore the impact of transition readiness on quality of life.
      METHODS: A total of 332 children with chronic diseases from two children's
      hospitals in Shanghai, China were enrolled. A self-designed demographic
      questionnaire, Pediatric Quality of Life Inventory 4.0 Generic Core Scales
      (PedsQLTM 4.0), and Self-Management and Transition to Adulthood with Rx=Treatment
      (STARx) Questionnaire were used to evaluate transition readiness and quality of
      life. RESULTS: The children with chronic diseases had a significantly lower total
      quality of life score than the national norm (74.66+/-15.85 vs 81.81+/-12.03;
      P<0.001). Doctor-patient communication and health care responsibilities (the
      child's abilities to take care of himself/herself and adaptation to the process
      of diagnosis and treatment from childhood to adulthood) were positively
      correlated with the scores on each dimension of quality of life (P<0.05).
      Duration of disease, time of absence from school within six months, and the
      number of types of drugs taken orally were negatively correlated with the total
      quality of life score (rs=-0.172, -0.236, and -0.280; P<0.05). The residence
      (urban or rural area), monthly family income, parents' educational level, and
      father's occupation had significant influence on children's quality of life
      (P<0.05). The hierarchical multiple regression analysis revealed that doctor
      patient communication and health care responsibilities led to a 14.3% increase in
      the explanation of the total variation in quality of life (P<0.001). CONCLUSIONS:
      Quality of life is not satisfactory in children with chronic diseases. Two
      domains of transition readiness, namely the abilities to communicate with health
      providers and health care responsibilities, are major factors influencing quality
      of life in these children.

PMID- 29335086
TI  - [Research progress in drug therapy for bronchopulmonary dysplasia in preterm
      infants].
AB  - Bronchopulmonary dysplasia (BPD) is the most common long-term complication in
      surviving extremely preterm infants. This may lead to pulmonary hypertension,
      increase late neonatal mortality, and cause abnormal neural development. There is
      still controversy over the efficacy, as well as advantages and disadvantages, of
      drug therapy for BPD in preterm infants. This article reviews the research
      progress in the drug therapy for BPD.

PMID- 29335087
TI  - [Research advances in the association between transient receptor potential cation
      channel 6 and kidney disease].
AB  - Transient receptor potential cation channel 6 (TRPC6) is a member of the
      transient receptor superfamily encoded by the TRPC6 gene and is widely expressed
      in tissues and organs of the human body, especially in the glomerular podocytes.
      TRPC6 interacts with various slit diaphragm (SD) proteins including podocin,
      nephrin, ACTN4, and CD2AP to maintain the normal structure and function of
      glomerular podocytes. Foot process fusion caused by podocyte damage due to
      various factors is the most important morphological change in kidney disease.
      This article reviews the biological function of TRPC6 and its effect on kidney
      disease.

PMID- 29335088
TI  - [Role of programmed death-1 in viral infectious diseases].
AB  - The research on the immunoregulatory effect of programmed death-1 (PD-1) in
      infectious diseases mainly focuses on chronic viral infection, but there are few
      studies on acute viral infection. In chronic viral infection, PD-1 is highly
      expressed on the surface of CD8+ T cells, which is a sign of CD8+ T cell
      depletion. Recent studies have shown that in chronic viral infection, PD-1 is
      also highly expressed on the surface of regulatory T cells and binds to
      programmed death-ligand 1 (PD-L1) on the surface of exhausted CD8+ T cells,
      resulting in a stronger inhibitory effect on CD8+ T cell immunity. Blocking the
      PD-1/PD-L1 signaling pathway between exhausted CD8+ T cells and regulatory T
      cells can significantly reverse the depletion of CD8+ T cells and greatly improve
      the antiviral effect of CD8+ T cells. However, the role of the PD-1/PD-L1
      signaling pathway in acute viral infection remains unknown. This article
      summarizes the latest research on PD-1 in infectious diseases and discusses its
      role in acute and chronic viral infection.

PMID- 29335089
TI  - Associations between clinical indicators of quality and aged-care residents.
AB  - Objectives To ascertain Australian multistate prevalence and incidence of five
      commonly collected clinical indicators of aged-care home quality and to measure
      associations between these clinical indicators and levels of care needs and
      consumer and staff satisfaction.Methods A retrospective analysis of national
      audit data collected from 426 facilities between 2015 and 2016 was performed.
      Regression models were used to examine associations between five clinical
      indicators (falls, pressure injury, physical restraint, unplanned weight loss and
      polypharmacy) and level of care needs measured by the Aged Care Funding
      Instrument (ACFI) and consumer and care staff survey responses.Results With the
      exception of polypharmacy, commonly collected negative clinical outcomes were
      rare events. Compared with care homes with <25% of residents having high-level
      care needs (high ACFI), homes with 25<75% high-ACFI residents had more
      occurrences of all negative clinical outcomes except pressure injury. Homes with
      >=75% high-ACFI residents reported the highest rates of polypharmacy (odds ratio
      1.48, 95% confidence interval 1.39 - 1.57). Falls, unplanned weight loss and
      pressure injury were inversely associated with satisfaction scores adjusted for
      residents' level of care needs.Conclusions This first Australian study of
      multistate clinical indicator data suggests interpretation of clinical indicators
      of aged-care home quality requires consideration of the level of residents' care
      needs.What is known about the topic? Many Australian aged-care providers use
      quality indicators (QI) through benchmarking companies or in-house programs. The
      five most widely used aged-care clinical QIs in Australia are falls, pressure
      injury, physical restraint, unplanned weight loss and polypharmacy. Prevalence
      and incidence of these QIs are highly variable among Australian studies. A
      consistent message in the international literature is that residents' clinical
      characteristics influence QI outcomes at baseline and may continue to influence
      outcomes over time. Study of associations between Australian aged-care home
      characteristics and QI outcomes has been limited.What does this paper add? This
      is the first Australian study of multistate clinical QI data. It is also the
      first to consider the level of resident care needs in the interpretation of
      clinical QI outcomes and exploration of the association between level of consumer
      and staff satisfaction and QI outcomes.What are the implications for
      practitioners? Understanding the connections between aged-care home
      characteristics, consumer and staff perceptions and clinical QIs is crucial in
      the meaningful interpretation of QI outcomes in context. With the recent
      introduction of the National Aged Care Quality Indicator Program, it is timely to
      review national policy, to gauge current quality of care and the measure of care
      quality in the sector, and to develop directions for possible research to inform
      and resolve debates regarding the potential influence and unplanned effects that
      such a program may have.

PMID- 29335090
TI  - Improving the efficacy of healthcare services for Aboriginal Australians.
AB  - Objective The aim of the present systematic review was to examine the enablers
      for effective health service delivery for Aboriginal Australians.Methods This
      systematic review was undertaken in accordance with the Preferred Reporting Items
      for Systematic Reviews and Meta-Analyses (PRISMA) statement. Papers were included
      if they had data related to health services for Australian Aboriginal people and
      were published between 2000 and 2015. The 21 papers that met the inclusion
      criteria were assessed using the Effective Public Health Practice Project Quality
      Assessment Tool for Quantitative Studies. Seven papers were subsequently excluded
      due to weak methodological approaches.Results There were two findings in the
      present study: (1) that Aboriginal people fare worse than non-Aboriginal people
      when accessing usual healthcare services; and (2) there are five enablers for
      effective health care services for Australian Aboriginal people: cultural
      competence, participation rates, organisational, clinical governance and
      compliance, and availability of services.Conclusions Health services for
      Australian Aboriginal people must be tailored and implementation of the five
      enablers is likely to affect the effectiveness of health services for Aboriginal
      people. The findings of the present study have significant implications in
      directing the future design, funding, delivery and evaluation of health care
      services for Aboriginal Australians.What is known about the topic? There is
      significant evidence about poor health outcomes and the 10-year gap in life
      expectancy between Aboriginal and non-Aboriginal people, and limited evidence
      about improving health service efficacy.What does this paper add? This systematic
      review found that with usual health care delivery, Aboriginal people experience
      worse health outcomes. This paper identifies five strategies in the literature
      that improve the effectiveness of health care services intended for Aboriginal
      people.What are the implications for practitioners? Aboriginal people fare worse
      in both experience and outcomes when they access usual care services. Health
      services intended for Aboriginal people should be tailored using the five
      enablers to provide timely, culturally safe and high-quality care.

PMID- 29335091
TI  - Repositioning interprofessional education from the margins to the centre of
      Australian health professional education ? what is required?
AB  - Objective This paper examines the implementation and implications of four
      development and research initiatives, collectively titled the Curriculum Renewal
      Studies program (CRS), occurring over a 6-year period ending in 2015 and focusing
      on interprofessional education (IPE) within Australian pre-registration health
      professional education.Methods The CRS was developed as an action-focused and
      participatory program of studies. This research and development program used a
      mixed-methods approach. Structured survey, interviews and extensive documentary
      analyses were supplemented by semi-structured interviews, focus groups, large
      group consultations and consensus building methods. Narrative accounts of
      participants' experiences and an approach to the future development of Australian
      IPE were developed.Results Detailed accounts of existing Australian IPE curricula
      and educational activity were developed. These accounts were published and used
      in several settings to support curriculum and national workforce development.
      Reflective activities engaging with the findings facilitated the development of a
      national approach to the future development of Australian IPE - a national
      approach focused on coordinated and collective governance and
      development.Conclusion This paper outlines the design of an innovative approach
      to national IPE governance and development. It explores how ideas drawn from
      sociocultural theories were used to guide the choice of methods and to enrich
      data analysis. Finally, the paper reflects on the implications of CRS findings
      for health professional education, workforce development and the future of
      Australian IPE.What is known about the topic? IPE to enable the achievement of
      interprofessional and collaborative practice capabilities is widely accepted and
      promoted. However, many problems exist in embedding and sustaining IPE as a
      system-wide element of health professional education. How these implementation
      problems can be successfully addressed is a health service and education
      development priority.What does this paper add? The paper presents a summary of
      how Australian IPE was conceptualised, developed and delivered across 26
      universities during the period of the four CRS studies. It points to strengths
      and limitations of existing IPE. An innovative approach to the future development
      of Australian IPE is presented. The importance of sociocultural factors in the
      development of practitioner identity and practice development is identified.What
      are the implications for practitioners? The findings of the CRS program present a
      challenging view of current Australian IPE activity and what will be required to
      meet industry and health workforce expectations related to the development of an
      Australian interprofessional- and collaborative-practice-capable workforce.
      Although the directions identified pose considerable challenges for the higher
      education and health sectors, they also provide a consensus-based approach to the
      future development of Australian IPE. As such they can be used as a blueprint for
      national development.

PMID- 29335092
TI  - The Journal of Cataract & Refractive Surgery: New look, new year.

PMID- 29335093
TI  - Changes in biomechanically corrected intraocular pressure and dynamic corneal
      response parameters before and after transepithelial photorefractive keratectomy
      and femtosecond laser-assisted laser in situ keratomileusis.
AB  - PURPOSE: To evaluate the changes in biomechanically corrected intraocular
      pressure (IOP) and new dynamic corneal response parameters measured by a dynamic
      Scheimpflug analyzer before and after transepithelial photorefractive keratectomy
      (PRK) and femtosecond laser-assisted laser in situ keratomileusis (LASIK).
      SETTING: Yonsei University College of Medicine and Eyereum Eye Clinic, Seoul,
      South Korea. DESIGN: Retrospective case series. METHODS: Medical records of
      patients having transepithelial PRK or femtosecond-assisted LASIK were examined.
      The primary outcome variables were biomechanically corrected IOP and dynamic
      corneal response parameters, including deformation amplitude ratio 2.0 mm,
      stiffness parameter at first applanation, Ambrosio relational thickness through
      the horizontal meridian, and integrated inverse radius before the procedure and 6
      months postoperatively. RESULTS: Of the 129 patients (129 eyes) in the study, 65
      had transepithelial PRK and 64 had femtosecond-assisted LASIK. No significant
      differences in biomechanically corrected IOP were noted before and after surgery.
      The deformation amplitude ratio 2.0 mm and integrated inverse radius increased,
      whereas the stiffness parameter at first applanation and the Ambrosio relational
      thickness through the horizontal meridian decreased after surgery (P < .001). The
      changes in deformation amplitude ratio 2.0 mm and integrated inverse radius were
      smaller in transepithelial PRK than femtosecond-assisted LASIK (P < .001). Using
      analysis of covariance, with refractive error change or corneal thickness change
      as a covariate, the changes in deformation amplitude ratio 2.0 mm and integrated
      inverse radius were smaller in transepithelial PRK than femtosecond-assisted
      LASIK (P < .001). CONCLUSIONS: The dynamic Scheimpflug analyzer showed stable
      biomechanically corrected IOP measurement before and after surgery. The changes
      in dynamic corneal response parameters were smaller with transepithelial PRK than
      with femtosecond-assisted LASIK, indicating less of a biomechanical effect with
      transepithelial PRK.

PMID- 29335094
TI  - Clinical outcomes of laser in situ keratomileusis with an aberration-neutral
      profile centered on the corneal vertex comparing vector planning with manifest
      refraction planning for the treatment of myopic astigmatism.
AB  - PURPOSE: To evaluate clinical outcomes of laser in situ keratomileusis (LASIK)
      with an aberration-neutral profile centered on the estimated visual axis
      (considering 70% of the pupil offset toward the corneal vertex) comparing vector
      planning with manifest refraction planning for the treatment of myopic
      astigmatism. SETTING: Muscat Eye Laser Center, Muscat, Sultanate of Oman, Muscat,
      Oman. DESIGN: Retrospective case series. METHODS: The outcomes were evaluated at
      a 6-month follow-up in eyes showing ocular residual astigmatism (ORA) over 0.75
      diopters (D) preoperatively. RESULTS: Eighty-five treatments were based on
      manifest astigmatism (preoperative sphere -2.11 D +/- 1.3 [SD], cylinder -0.90 +/
      1.0 D), and 79 treatments were based on vector planning (preoperative sphere 
      2.46 +/- 1.5 D, cylinder -0.78 +/- 0.79 D). At a 6-month follow-up, 128 patients
      (164 eyes) were evaluated and no significant differences were observed between
      the 2 groups in terms of difference between corrected distance visual acuity and
      uncorrected distance visual acuity (UDVA) (P = .1, t test and Fisher exact test
      Snellen lines 1 or better, P = .4) and postoperative UDVA (P = .05, t test and
      Fisher exact test for UDVA 20/16 or better, P = .3). Significant differences were
      observed between the 2 groups in terms of achieved spherical equivalent (P =
      .04), corneal toricity, and ORA (P < .001, t test and Fisher exact test for ORA
      <=0.75 D, P < .001). CONCLUSION: Performing LASIK for myopic astigmatism with the
      vector planning approach resulted in comparable visual outcomes to manifest
      refraction planning.

PMID- 29335095
TI  - Vector analysis of astigmatic changes and optical quality outcomes after
      wavefront-guided laser in situ keratomileusis using a high-resolution
      aberrometer.
AB  - PURPOSE: To assess the ocular optical quality results as well as the astigmatic
      changes after wavefront-guided laser in situ keratomileusis (LASIK) in eyes with
      myopic astigmatism. SETTING: Instituto Clinico-Quirurgico Oftalmologico, Bilbao,
      Vizcaya, Spain. DESIGN: Prospective case series. METHODS: Thirty-three eyes
      having wavefront-guided LASIK with the Star S4IR excimer laser combined with the
      iDesign system were enrolled in the study. Changes in visual acuity, refraction,
      higher-order aberrations, and ocular scattering index (OSI) were evaluated during
      a 3-month follow-up. The Alpins method was used to analyze the astigmatic
      changes. RESULTS: A significant reduction was observed in refraction (P < .001),
      with significant improvement in uncorrected (UDVA) and corrected (CDVA) distance
      visual acuities (P < .001). All eyes had a spherical equivalent within +/-0.50
      diopter (D) and UDVA of 20/25 or better at 90 days after surgery. A total of
      27.3% of eyes gained lines of CDVA. No significant changes were observed in
      primary coma and spherical aberration (P >= .551). Likewise, no significant
      changes were observed in OSI (P = .361), with a mean 90-day postoperative value
      of 0.66 +/- 0.58 (SD). A significant change to negative values of the magnitude
      of error (P = .007) and a significant decrease in the correction index (P = .004)
      were observed during the follow-up, with mean 90-day postoperative values of 
      0.24 +/- 0.28 D and 0.86 +/- 0.17 D, respectively. CONCLUSION: Wavefront-guided
      LASIK using a high-resolution aberrometer provided safe and efficacious
      correction of myopic astigmatism, with preservation of the ocular optical
      quality.

PMID- 29335096
TI  - Clinically significant laser in situ keratomileusis flap striae.
AB  - PURPOSE: To describe the incidence, risk factors, and outcomes before and after
      irrigation of clinically significant laser in situ keratomileusis (LASIK) flap
      striae. SETTING: Multisurgeon multicenter standardized protocol practice. DESIGN:
      Retrospective case-control series. METHODS: Eyes with striae necessitating flap
      relift and irrigation were identified. Preoperative, intraoperative, and
      postoperative variables were collected. Incidence, risk factors, and outcomes
      were assessed. RESULTS: Of the 109 403 eyes that had LASIK, the incidence of
      striae-treated eyes was 0.79% (n = 875), with 8.7% irrigated the first hour after
      surgery. The preoperative spherical equivalent (SE) and ablation depth
      exponentially increased the striae risk (R2 = 0.9674; P < .001). Striae induced a
      small hyperopic shift that reversed after the relift (mean 0.22 diopter [D] +/-
      0.52 [SD] versus -0.02 +/- 0.45 D) (P < .001). After relifting, 68.0%, 87.0%, and
      96.0% of eyes had an uncorrected distance visual acuity (UDVA) of 20/20, 20/25,
      20/40 or better versus 25.0%, 55.0%, and 84.0%, respectively, before the relift
      (P < .001). Thirteen percent fewer striae-treated eyes achieved a UDVA of 20/20.
      Before relifting, 51.0% of striae eyes lost 1 or more lines of corrected distance
      visual acuity, with a safety index reverting to control values (0.99 versus 1.00)
      (P > .05) after the relift. A laser refractive enhancement was performed in 6.28%
      of relifted striae eyes versus 3.04% in nonstriae control eyes. CONCLUSIONS: Flap
      striae requiring surgeon intervention occurred in 0.79% of eyes. Higher
      preoperative SE values were associated with an exponential increase risk for
      striae. Treatment by lifting and irrigation significantly improved the accuracy,
      efficacy, and safety to a level close to that of contralateral control eyes,
      although striae-treated eyes were more likely to need excimer laser retreatment.

PMID- 29335097
TI  - Aspheric versus wavefront-guided aspheric photorefractive keratectomy in eyes
      with significant astigmatism.
AB  - PURPOSE: To compare the refractive and higher-order aberrations (HOAs) outcomes
      after photorefractive keratectomy (PRK) in patients with significant astigmatism
      using aspheric versus wavefront-guided aspheric profiles. SETTING: Ophthalmic
      Research Center and Department of Ophthalmology, Shahid Beheshti University of
      Medical Sciences, Negah Eye Hospital, Tehran, Iran. DESIGN: Prospective
      randomized case series. METHODS: One eye of each patient with a refractive
      astigmatism more than 2.00 diopters (D) randomly received aspheric PRK. In the
      other eye, wavefront-guided and aspheric treatment was performed using a
      personalized treatment advanced algorithm. Visual acuity, refractive errors, and
      HOAs were compared between the 2 groups preoperatively and 12 months
      postoperatively. RESULTS: The study comprised 32 patients (64 eyes). The mean
      preoperative refractive astigmatism was -4.07 D +/- 1.64 (SD) and -4.02 +/- 1.55
      D in the aspheric group and wavefront-guided aspheric group, respectively (P =
      .2). The mean postoperative astigmatism was -0.46 +/- 0.37 D and -0.82 +/- 0.53 D
      in the aspheric group and wavefront-guided aspheric group, respectively (P =
      .02). Postoperatively, the root mean square of total HOAs was significantly
      increased in both groups. However, compared with wavefront-guided aspheric PRK,
      aspheric PRK induced fewer HOAs (P = .003). CONCLUSIONS: In eyes with high
      astigmatism, post-PRK residual astigmatism was lower in the aspheric group than
      in the wavefront-guided aspheric group. The increase in HOAs was significantly
      higher in the wavefront-guided aspheric group than in the aspheric group.

PMID- 29335098
TI  - Factors affecting corneal incision position during femtosecond laser-assisted
      cataract surgery.
AB  - PURPOSE: To compare the expected versus actual position and dimension of corneal
      incisions during femtosecond laser-assisted cataract surgery. SETTING: Private
      Ophthalmic Clinic, Sydney, NSW, Australia. DESIGN: Retrospective case series.
      METHODS: Video recordings of femtosecond laser-assisted cataract surgery with a
      Lensx laser were reviewed. The deviation of the main and 2 secondary incisions
      from the expected position were correlated with globe tilt, globe displacement,
      and biometric data. The globe tilt was inferred from anterior capsule tilt. Globe
      displacement was measured. The Softfit contact lens thickness used in the patient
      interface was measured separately. RESULTS: The primary incision internal and
      external exits were within 142 MUm +/- 70 (SD) and 151 +/- 75 MUm of the planned
      position. The dimensions and position did not correlate with biometric variables.
      The superior secondary incision external exit was displaced centrally (321 +/- 84
      MUm) and the internal exit was displaced peripherally (84 +/- 102 MUm). The
      inferior secondary incision external exit was displaced centrally (278 +/- 142
      MUm) and the internal exit was displaced peripherally (190 +/- 133 MUm).
      Multivariate analysis showed that the external and internal exits of the superior
      (adjusted r2 = 0.36, P < .001; r2 = 0.15, P < .001) and inferior secondary
      incisions (r2 = 0.67, P < .001; r2 = 0.46, P < .001) correlated with globe tilt
      and displacement. CONCLUSIONS: The primary incisions were close to the expected
      dimensions. The secondary incision position was affected by eye tilt and
      eccentric docking. These could potentially be improved with optical coherence
      tomography guidance.

PMID- 29335099
TI  - Femtosecond laser-assisted cataract surgeries reported to the European Registry
      of Quality Outcomes for Cataract and Refractive Surgery: Baseline
      characteristics, surgical procedure, and outcomes.
AB  - PURPOSE: To describe a large cohort of femtosecond laser-assisted cataract
      surgeries in terms of baseline characteristics and the related outcomes. SETTING:
      Eighteen cataract surgery clinics in 9 European countries and Australia. DESIGN:
      Prospective multicenter case series. METHODS: Data on consecutive eyes having
      femtosecond laser-assisted cataract surgery in the participating clinics were
      entered in the European Registry of Quality Outcomes for Cataract and Refractive
      Surgery (EUREQUO). A trained registry manager in each clinic was responsible for
      valid reporting to the EUREQUO. Demographics, preoperative corrected distance
      visual acuity (CDVA), risk factors, type of surgery, type of intraocular lens,
      visual outcomes, refractive outcomes, and complications were reported. RESULTS:
      Complete data were available for 3379 cases. The mean age was 64.4 years +/- 10.9
      (SD) and 57.8% (95% confidence interval [CI], 56.1-59.5) of the patients were
      women. A surgical complication was reported in 2.9% of all cases (95% CI, 2.4
      3.5). The mean postoperative CDVA was 0.04 +/- 0.15. logarithm of the minimum
      angle of resolution. A biometry prediction error (spherical equivalent) was
      within +/-0.5 diopter in 71.8% (95% CI, 70.3-73.3) of all surgeries.
      Postoperative complications were reported in 3.3% (95% CI, 2.7-4.0). Patients
      with good preoperative CDVA had the best visual and refractive outcomes; patients
      with poor preoperative visual acuity had poorer outcomes. CONCLUSIONS: The visual
      and refractive outcomes of femtosecond laser-assisted cataract surgery were
      favorable compared with manual phacoemulsification. The outcomes were highly
      influenced by the preoperative visual acuity, but all preoperative CDVA groups
      had acceptable outcomes.

PMID- 29335100
TI  - Risk factors for and management of pupillary intraocular lens capture after
      intraocular lens transscleral fixation.
AB  - PURPOSE: To analyze risk factors and management of pupillary intraocular lens
      (IOL) capture after IOL transscleral fixation. SETTING: Department of
      Ophthalmology, Seoul National University Hospital, Seoul, South Korea. DESIGN:
      Retrospective case series. METHODS: A chart review was performed of patients who
      had transscleral fixation of IOLs between January 1, 2012, and December 31, 2013.
      Eyes were divided into 2 groups depending on whether the IOL was pupillary
      captured. Perioperative corrected distance visual acuity (CDVA), intraocular
      pressure (IOP), spherical equivalent (SE) with refraction, axial length (AL), and
      total follow-up time were compared between the 2 groups. Ultrasound biomicroscopy
      images were used to analyze iris morphology and IOL position. RESULTS: The chart
      review identified 138 patients, 112 patients of whom were included in this
      analysis. The preoperative and final mean CDVA, IOP, SE, AL, and most iris
      morphologic parameters were not significantly different between the 2 groups. In
      the pupillary capture IOL group, the mean age of patients with was younger, the
      anterior chamber depth (ACD) was narrower, and the rate of reverse pupillary
      block was higher (P = .003, P = .03, and P = .016, respectively). Intraocular
      lens decentration in the captured group was significantly larger (P = .002).
      Multiple logistic regression analysis showed that ACD, reverse pupillary block,
      and main decentration were associated with pupillary capture of the IOL.
      CONCLUSIONS: Pupillary capture of an IOL occurred more in eyes with reverse
      pupillary block and poor IOL positioning. Accordingly, laser iridotomy must be
      considered for treatment.

PMID- 29335101
TI  - Outcomes and complication rates of primary resident-performed cataract surgeries
      at a large tertiary-care county hospital.
AB  - PURPOSE: To identify the preoperative risk factors, intraoperative events, and
      postoperative complications increasing the risk for poor visual outcomes in
      resident-performed cataract surgeries at a tertiary-care county hospital.
      SETTING: Ben Taub General Hospital, Houston, Texas, USA. DESIGN: Retrospective
      case series. METHODS: Resident-performed cataract surgeries were analyzed for
      risk factors, comorbidities, and intraoperative and postoperative complications.
      The main outcome measures were preoperative and postoperative uncorrected
      distance visual acuity and corrected distance visual acuity (CDVA), which were
      correlated with preoperative demographics, intraoperative and postoperative
      events, and resident training level. The data were subdivided into cases without
      events and cases with events to determine which complications led to poor visual
      outcomes. RESULTS: The study analyzed 1290 resident-performed cataract surgeries.
      The mean visual acuity improved significantly after surgery in all patients (P <
      .001), with 80.5% of patients without complications and 70.7% with complications
      attaining a CDVA of 20/40 or better (P < .002). Poor visual outcomes were
      associated with alpha-antagonist use (P = .043) and pseudoexfoliation syndrome (P
      = .001). The most common intraoperative complications were vitreous loss (6.7%)
      and posterior capsule tear (7.0%). The mean postoperative visual acuity did not
      vary by trainee year, and the rate of dropped nucleus during surgery declined as
      residents progressed in training (P < .05). All other complication rates were
      similar between levels of training. CONCLUSION: Despite more complicated
      cataracts and advanced comorbidities, primary resident-performed cataract surgery
      in a tertiary-care county hospital system achieved visual outcomes and
      complication rates similar to those found in other training hospitals.

PMID- 29335102
TI  - Comparison of 2 laser fragmentation patterns used in femtosecond laser-assisted
      cataract surgery.
AB  - PURPOSE: To evaluate the effect of fragmentation patterns (pie pattern versus
      grid pattern) on effective phacoemulsification time (EPT). SETTING: Department of
      Ophthalmology, Goethe University, Frankfurt am Main, Germany. DESIGN:
      Retrospective case series. METHODS: Eyes that had femtosecond laser-assisted
      cataract surgery were included. One half of the group was treated with the pie
      pattern. The preoperative lens density was evaluated by Scheimpflug imaging
      (Pentacam). Then, the eyes treated with the grid pattern were matched to the pie
      pattern group based on lens density (Scheimpflug imaging). RESULTS: The study
      comprised 150 eyes (75 in the pie-pattern group and 75 in the grid pattern
      group). The mean patient age was 66 years +/- 10.67 (SD). The Scheimpflug density
      zone was 10.05% +/- 1.52%. The mean EPT was 6.63 +/- 5.41 seconds for the pie
      pattern, significantly higher than the 4.26 +/- 6.99 seconds for the grid pattern
      (P < .01, Wilcoxon rank-sum test). The number of eyes with EPT = 0 was
      significantly higher with grid pattern (37 for grid versus 1 for pie, P < .01,
      chi2 test). Regression analysis showed that the EPT was significantly dependent
      on lens density for both methods (P = .045 for pie versus P < .01 for grid). In
      eyes with a lens density higher than 12% (9 eyes in each group), the pie pattern
      showed significantly lower EPT (P = .02, Wilcoxon rank-sum test). CONCLUSIONS: In
      cases of low to moderate lens density, grid fragmentation pattern should be used
      because the EPT was significantly lower and a significantly higher number of eyes
      did not require further emulsification. However, in eyes with high density
      (>12%), pie-pattern fragmentation is recommended.

PMID- 29335103
TI  - New objective lens density quantification method using swept-source optical
      coherence tomography technology: Comparison with existing methods.
AB  - PURPOSE: To assess a new objective cataract grading method based on lens
      densitometry on swept-source optical coherence tomography (SS-OCT) scans provided
      by the IOLMaster 700. SETTINGS: Rothschild Foundation, Paris, France. DESIGN:
      Prospective case series. METHODS: All patients consulting for cataract evaluation
      who provided their consent to participate in the study were included. A history
      of eye surgery, corneal or retinal disorders, and ocular dryness were exclusion
      criteria. The average lens densitometry was measured with SS-OCT scans using
      ImageJ software. The ocular scatter index (OSI) measured with a double-pass
      aberrometer (Optical Quality Analysis System), the Pentacam nucleus staging
      (hereafter referred to as nuclear staging) score, and mean nuclear staging were
      also measured and compared with the mean lens densitometry. RESULTS: One hundred
      ten eyes (51 with cataract and 59 controls) were included. The average lens
      densitometry measurements were repeatable (P = .99, analysis of variance). The
      repeatability limit was 2.50 pixel units. The average lens density was correlated
      with the OSI (r2 = 0.52, P < .01), nuclear staging score (r2 = 0.75, P < .01),
      and mean nuclear staging (r2 = 0.41, P < .01). An average lens density greater
      than 82.9 pixel units was the cutoff threshold for cataract, with a sensitivity
      of 73.9% and a specificity of 91.2%. CONCLUSIONS: The average lens density
      measured by SS-OCT was a repeatable and reliable objective cataract grading
      method. It was correlated with OSI measurement. If the average lens density was
      greater than 82.9 pixel units and the patient reported visual impairment,
      cataract surgery might be discussed.

PMID- 29335104
TI  - Vision-related quality of life and dependency in French keratoconus patients:
      Impact study.
AB  - PURPOSE: To assess the quality of life in French keratoconus patients. SETTING:
      Fifty-seven Keratoconus National Reference Centers across France. DESIGN:
      Prospective case series. METHODS: Patients completed the National Eye Institute
      Visual Functioning Questionnaire-25 (NEI VFQ-25) and a French validated
      questionnaire on disability and dependency from February to June 2012 when they
      came for an ophthalmic examination at 57 participating centers across France. An
      ocular examination including refraction, corneal topography, pachymetry, and
      slitlamp biomicroscopy was performed. The composite or global NEI VFQ-25 score
      and the proportion of patients who were dependent (defined by the difficulties
      with activities of daily living) because of keratoconus were the main evaluation
      criteria in this study. RESULTS: The study comprised 550 keratoconus patients.
      Women, corrected distance visual acuity worse than 20/40, steep keratometry
      higher than 52.0 diopters, history of surgery (corneal transplant, intrastromal
      corneal ring segments, or corneal crosslinking), and more severe keratoconus
      according to the Amsler-Krumeich classification were associated with an
      increasingly negative impact on quality of life (overall scores are significantly
      lower). Moreover, 4.9% of participants reported having changed their jobs because
      of keratoconus and 7.8% received keratoconus-related disability. Sixty-nine
      (12.5%) patients reported having difficulties with activities of daily living and
      are considered dependent. CONCLUSION: Keratoconus was associated with a
      significant reduction in quality of life but it did not result in social
      exclusion.

PMID- 29335105
TI  - Optimization and comparison of a 0.7 mm tip with the 0.9 mm tip on an active
      fluidics phacoemulsification platform.
AB  - PURPOSE: To assess the effect of varying levels of torsional power on
      phacoemulsification efficiency using an active-fluidics phacoemulsification
      platform with a 0.7 mm Sonata tip. SETTING: John A. Moran Eye Center
      Laboratories, University of Utah, Salt Lake City, Utah, USA. DESIGN: Experimental
      study. METHODS: A 0.7 mm tip was used to emulsify 2.0 mm porcine lenses that had
      been hardened in formalin. The torsional power was varied from 10% to 100% at
      intervals of 10%, and efficiency and chatter were recorded. A comparison of the
      0.7 mm tip with the 0.9 mm Balanced tip was also performed. Using a torsional
      power setting of 90% and 100%, the 0.7 mm tip and the 0.9 mm tip efficiency times
      were recorded. RESULTS: The study showed an increase in efficiency as torsional
      power increased. The relationship was linear and more efficient up to 90% (R2 =
      .8025, P = .0005). Chatter was only observed at a torsional power setting of 60%.
      In addition, a head-to-head comparison of the 0.7 mm tip with the 0.9 mm tip
      showed that both tips were statistically similar in efficiency times, despite the
      smaller diameter of the 0.7 mm tip. CONCLUSIONS: The optimum torsional power
      setting with the Centurion platform in conjunction with the 0.7 mm tip was 90%.
      The efficiency of the 0.7 mm tip and the 0.9 mm tip was statistically similar.

PMID- 29335106
TI  - Preoperative optimization of ocular surface disease before cataract surgery.
AB  - An impaired ocular surface adversely affects preoperative planning for cataract
      surgery, including intraocular lens (IOL) calculations, toric IOL axis and
      magnitude estimates, keratometry, and topography measurements. It also increases
      surgical difficulty. We performed a review to evaluate the connection between
      cataract surgery and dry eye and to determine the best management for these
      patients. Of the 16 papers included in this review, 6 were randomized controlled
      trials. Cataract surgery was shown to worsen ocular parameters and aggravate dry
      eye disease. Physicians should recognize and aggressively treat cataract patients
      with poor prognostic factors and/or with existing dry-eye disease. Increased
      incision extent, operation time, irrigation, and microscopic-light exposure time
      decreased the tear breakup time and mean goblet cell density. Postoperatively,
      the use of eyedrops was associated with worsening of goblet cell density; hence,
      these medications should be tapered off when no longer needed.

PMID- 29335107
TI  - Surgical removal of dystrophic calcification on a silicone intraocular lens in
      association with asteroid hyalosis.
AB  - We present a case of successful removal of late calcium deposition on the
      posterior surface of a silicone intraocular lens (IOL) optic in association with
      asteroid hyalosis using a surgical technique that included pars plana vitrectomy,
      a lighted pick, and a modified silicone-tipped cannula. The lighted pick provided
      the most efficient and complete removal of calcium deposits. Postoperatively, the
      dystrophic calcification was removed and the IOL optic was clear at 6 months
      follow-up. The patient's symptoms resolved and uncorrected distance visual acuity
      returned to 20/20. This method can be considered in patients with dystrophic
      calcification of a silicone IOL in association with asteroid hyalosis and might
      avoid the need for IOL exchange and its associated complications and uncertain
      refractive outcomes.

PMID- 29335108
TI  - Cataract morphology and risk for glaucoma after cataract surgery in infants with
      unilateral congenital cataract.

PMID- 29335109
TI  - Trypan blue-assisted microinvasive glaucoma surgery.

PMID- 29335110
TI  - December consultation #2.

PMID- 29335111
TI  - Corneal asymmetry associated with stromal opacity after previous laser in situ
      keratomileusis: December consultation #1.

PMID- 29335112
TI  - December consultation #3.

PMID- 29335114
TI  - December consultation #5.

PMID- 29335113
TI  - December consultation #6.

PMID- 29335115
TI  - December consultation #4.

PMID- 29335116
TI  - Editor's Comment.

PMID- 29335117
TI  - December consultation #7.

PMID- 29335118
TI  - Management of subluxated intraocular lens-capsular bag complex.

PMID- 29335119
TI  - Reply.

PMID- 29335120
TI  - Differentiating retinal tear and detachment rate by axial length to identify at
      risk patients having neodymium:YAG capsulotomy.

PMID- 29335121
TI  - Letter to the Editor: Proceedings from the USDA and National Dairy Council
      Collaborative Research Planning Meeting Held August 24, 2016.

PMID- 29335122
TI  - ?

PMID- 29335123
TI  - ?

PMID- 29335124
TI  - [The reception, a prerequisite of the encounter: a political question].
AB  - The reception of a patient in psychiatry is a stage which consists of more than a
      single initial contact between a person suffering psychologically and a
      caregiver. This time can open the way to an encounter, without which a care
      relationship cannot be established. The reception as a paradigm of psychiatric
      care questions the concept of this care, at a time when caregivers cannot avoid
      the question of their political engagement.

PMID- 29335125
TI  - [The end of the asylum, a change in representations].
AB  - Through the major changes which the psychiatric hospital has undergone throughout
      history, the question is raised of the identity of caregivers, what the
      psychiatric asylum provides as a response to mental illness, and the function of
      the asylum as a place for receiving and then caring for patients, within society.
      These radical changes, which undermine the narcissism of caregivers, have
      consequences both within the psychiatric hospital and society as a whole.
      Consequences which question the very notion of care in a post-modern society.

PMID- 29335126
TI  - [Reception of the patient in psychiatry: overcoming the narcissistic test of the
      caregiver].
AB  - The theme of the encounter is addressed through the question of the reception of
      the patient. This encounter forces the caregiver to consider his or her own
      identity faced with the patient, to adjustments which can elude narcissistic
      doubts by resorting to the standardisation of care. Possible ways for the
      construction of a joint project are then considered. A 'common illusion' of care,
      which ensures that the encounter, a prelude to the possibility of care, is
      achieved.

PMID- 29335127
TI  - [Accessing the sensitive part of the Being before us].
AB  - The acceleration of the standardisation of care and the dominance of the quality
      approach, since the 1990s, have brought significant changes to nursing practices,
      the different therapeutic approaches and the 'place' of caregivers with regard to
      the patient. In this context of modern psychiatry which must comply with all
      kinds of recommendations, what is the situation of the patient suffering from
      psychosis, who would previously have been supported over the long term in a
      psychopathological process? The encounter, envisaged as an opening, is placed at
      the heart of the therapeutic relationship.

PMID- 29335129
TI  - [A tale of two encounters].
AB  - The moving testimony of a patient shows the impact which a successful encounter
      can have. Beyond the positive clinical consequences, her rediscovered motivation
      and pleasure are the essential drivers which have guided her along the pathway of
      reconstruction. A tale of two encounters which have marked her life course.

PMID- 29335128
TI  - [Risking the encounter].
AB  - In their daily practice, psychiatric caregivers seek an encounter with the
      patient. This involves trying to understand the patient's suffering, to give
      meaning and to make the clinical connection. This equates to constructing
      together. Some care organisations are working to create spaces within units which
      are suited to receiving patients with an atmosphere favouring the encounter. The
      story of Baptiste illustrates this approach. Testimony.

PMID- 29335130
TI  - [Body marking in psychosis].
AB  - Patients with psychosis speak of an uneasy relationship with their body. Between
      feelings of too little and too much, for them it is a matter of trying to suture
      an image which is not always unified, a body which they are not always sure they
      have. The attentive clinician will attempt to support the solutions of each
      psychotic patient to maintain their body, beyond the death drive which pushes
      them to tear it apart.

PMID- 29335132
TI  - ?

PMID- 29335131
TI  - [Call for reinforcements, care to support clinical pertinence].
AB  - In their day-to-day practice, psychiatric caregivers are frequently confronted
      with difficult clinical situations, or crises, which require a rapid and
      appropriate nursing response. While most of these situations are managed and
      contained by the professionals present, others will require, depending on their
      criticality, outside help in order to guarantee greater clinical pertinence and a
      safe environment.

PMID- 29335133
TI  - ?

PMID- 29335134
TI  - ?

PMID- 29335135
TI  - [Nursing home, caregiving practice and new work organisation].
AB  - The recent ageing of the population is resulting in a corresponding increase in
      the functional dependence of elderly people. Nursing homes hosting this specific
      population must adapt to this new profile of resident and their arrival at an
      increasingly older age. Caregiving tasks are becoming more cumbersome affecting
      the working conditions of caregivers who also face the new management approaches
      which are imposed.

PMID- 29335136
TI  - [Life project of residents and institutional approach in nursing homes].
AB  - The life project in a nursing home involves all the players concerned: first of
      all, the resident, then the caregivers, the families and the institution. This
      unifying tool, organised around the elderly, helps to develop collective
      competencies, favours the integration of new residents and reassures families.
      This article presents a nursing home's experience of setting up a life project.

PMID- 29335137
TI  - [Nutritional status of residents of a nursing home and optimisation of the
      working time of caregivers].
AB  - The lack of time to devote to care is a frequent complaint of nurses and nursing
      assistants. The results of a study show that an improvement in the nutritional
      status of nursing home residents could help to improve their quality of life and
      to optimise the working time of the nursing teams, thanks to the reduction of
      pressure ulcers, diarrhoea, falls, fractures and infections.

PMID- 29335138
TI  - [Intrafamily conflicts and family-caregiver tensions in a nursing home].
AB  - Conflicts between families and caregivers in a nursing home have multiple causes
      centred (but not exclusively) on the interest of the resident. Intrafamily
      conflicts can lead to tensions between families and caregivers. Alzheimer's
      disease changes the relations with the patient's family members when they are
      involved in the care, which can lead to a division within the family. This
      article discusses the sources of difficulties between families and caregivers and
      ways of managing and above all preventing them.

PMID- 29335139
TI  - [The analogon, a caregiving resource in geriatric psychiatry].
AB  - Few caregivers know what analogons are, yet they use them on occasion,
      intuitively, for the benefit of their patients. An analogon, an identifying
      object, enables patients with cognitive disorders to 'decipher' their environment
      and find meaning in it. Caregivers sometimes use analogons without being aware of
      the theory behind them.

PMID- 29335140
TI  - [The sexualisation of the care relationship by the patient in gerontology].
AB  - The expression of the sexuality of the ageing patient in the care setting,
      particularly when it concerns the genital area and involves the caregiver without
      he or she being aware, constitutes a critical situation for the geriatric teams.
      A psychodynamic reading of these situations is important for the caregiving teams
      in order to optimise the somatic treatment and to prevent the risk of an
      unsuitable reactive treatment. This article presents a clinical case as an
      example.

PMID- 29335141
TI  - ?

PMID- 29335142
TI  - ?

PMID- 29335143
TI  - ?

PMID- 29335144
TI  - ?

PMID- 29335145
TI  - [The place of separations in a child's development].
AB  - The issue of separation follows a specific process in the course of a child's
      development. Putting in place the intersubjective distance and primitive links
      marks the process of differentiation, falling short of actual separation.
      Therapeutic separations can be restorative and structuring, under certain
      conditions. The role of professionals is to ensure that the separations do not
      simply constitute 'bad encounters'.

PMID- 29335146
TI  - [Supporting the encounter of mothers suffering from borderline conditions with
      their baby].
AB  - Mothers suffering from borderline conditions are overwhelmed by emotions. Their
      interactions are tainted with qualitative discontinuities, unpredictable for
      infants. These high-risk situations must not be trivialised. They are
      characterised by the importance of providing rapid support to the baby and by the
      existence of maternal suffering. The infant's basic needs guide the professionals
      working with these families.

PMID- 29335147
TI  - [Pre- and postnatal support through haptonomy].
AB  - Pre- and postnatal haptonomy constitutes a quality form of support for babies and
      their parents, from the final months of pregnancy through to the acquisition of
      walking. It contributes to the development of infants' emotional, sensory and
      tonic-postural security, enabling them to start to move and engage with
      confidence in life and in relationships.

PMID- 29335148
TI  - [Access to language, encounters and separations].
AB  - Access to language is part of the extension of a preverbal relationship with one
      or several partners. This relationship, present from birth, is founded on
      extremely sophisticated innate competencies. Oral language is both an instrument
      of encounter with those around us and a means of separating ourselves from others
      harmlessly, thanks to the symbolic value of words and the process of
      internalisation which they allow.

PMID- 29335149
TI  - [Learning to separate together, the separation-individuation group].
AB  - The 'separation-individuation' group is offered to children aged between three
      and five, in outpatient consultations with a paediatric psychiatrist. It was
      created following the testimonies of early childhood professionals describing the
      feeling on the part of parents of being torn from their child, during the first
      year of school. Open and held on a weekly basis, it is combined with a parents'
      meeting organised simultaneously. The individualised group tool supports the
      separation-individuation process when this is particularly painful, for the child
      and the parents.

PMID- 29335150
TI  - [Birth and separation, questioning caesarean deliveries on maternal request].
AB  - Clinical practice and literature highlight the emergence and the growth in the
      number of caesareans carried out on the request of the mother without medical
      indication. For some women, a vaginal delivery is an anachronism, while for
      others it is a necessary passage towards motherhood. A reflection was carried out
      to illustrate the singularity behind these requests and attempt to overcome the
      'for' and 'against' divide.

PMID- 29335151
TI  - [Tools to overcome anxiety in paediatric surgery].
AB  - An association of caregivers carried out several actions to combat children's
      anxiety in paediatric surgery, including anaesthetic masks to cover in stickers,
      a tactile application on the operating pathway and a cuddly toy in the recovery
      room. These tools help children at the moment of being separated from their
      parents and all along their care pathway. They also encourage caregivers to
      adjust their practices to improve the care provided to the families.

PMID- 29335152
TI  - ["I foster babies awaiting adoption."]
AB  - A mother's decision to give up a child is followed by a two-month period during
      which she may go back on her decision. During this time, the baby may be cared
      for in a care home or placed with a specialist foster family. An interview with
      Christiane Hamel, a retired children's nurse who has chosen to foster children in
      her home.

PMID- 29335153
TI  - [The sitting position during peripheral venipunctures in young children, a
      practice to develop].
AB  - The children's nurse has several missions including that of caring for the child
      in a holistic approach, ensuring their physical safety and psychological
      security. When performing peripheral venipunctures in young children, caregivers
      must implement strategies to relieve pain and prevent psychological traumas which
      may generate stress for subsequent care procedures. In a paediatric unit, their
      observations and analysis have improved children's experience of this invasive
      procedure, with a need for less restraint. In this context, the sitting position
      seems beneficial for the young patient.

PMID- 29335154
TI  - Local administration of Tiludronic Acid downregulates important mediators
      involved in periodontal tissue destruction in experimental periodontitis in rats.
AB  - OBJECTIVE: The purpose of this study was to evaluate whether local administration
      of TIL could influence the expression of the inflammatory mediators IL-1beta, TNF
      alpha, MMP-8 and COX-2 in rats with experimental periodontitis (EP). METHODS:
      Twenty-four adult male rats (Rattus norvegicus, albinus, Wistar) were assigned to
      groups C, EP, EP-TIL (CControl group, EP-Periodontitis groups). On EP groups, a
      ligature was placed around maxillary 2nd molars on day 1. On group EP-TIL, 20 MUL
      of TIL solution (1 mg/kg body weight) was injected into the subperiosteal palatal
      area adjacent to the maxillary 2nd molar every other day until euthanasia (day
      11). Alveolar bone loss was morphometrically analyzed. mRNA expressions of IL
      1beta, TNF-alpha, MMP-8 and COX-2 were assessed by qPCR. IL-1beta, TNF-alpha, MMP
      8 and COX-2 were immunohistochemically analyzed. Data were analyzed
      statistically. RESULTS: Group EP-TIL presented reduced alveolar bone loss when
      compared with group EP (p < 0.05). Group EP-TIL presented decreased mRNA
      expressions of IL-1beta, TNF-alpha, MMP-8 and COX-2 and reduced immunolabeling of
      IL-1beta, TNF-alpha and MMP-8 when compared with group EP (p < 0.05). No
      differences regarding the immunolabeling of COX-2 were found when group EP-TIL
      was compared with the other groups (p > 0.05). CONCLUSION: Within the limits of
      this study, it can be concluded that local administration of TIL downregulates
      important mediators involved in periodontal tissue destruction in ligature
      induced periodontitis in rats.

PMID- 29335155
TI  - Investigating the potential impact of dose banding for systemic anti-cancer
      therapy in the paediatric setting based on pharmacokinetic evidence.
AB  - BACKGROUND: To make systemic anti-cancer therapy (SACT) preparation more
      practicable, dose-banding approaches are currently being introduced in many
      clinical centres. The present study aimed to determine the potential impact of
      using recently developed National Health Service in England (NHSE) dose-banding
      tables in a paediatric setting. METHODS: Using pharmacokinetic parameters
      obtained from 385 drug administrations in 352 children aged from 1 month to 18
      years, treated with five drugs (dactinomycin, busulfan, carboplatin,
      cyclophosphamide and etoposide), individual exposures (area under the plasma drug
      concentration versus time curve; AUC) obtained using doses rounded according to
      the published NHSE tables were calculated and compared with those obtained by
      standard dose calculation methods. RESULTS: For all five drugs, the relative
      variation between the NHSE dose and the recommended dose (RecDose) (standard
      individually calculated dose) was between -6% and +5% as expected. In terms of
      AUC, there was no statistically significant difference in precision between
      exposures obtained by the RecDose and those obtained with dose banding (absolute
      value of relative difference 15-34%). CONCLUSION: Based on pharmacokinetic data
      for these five drugs, the results generated support the implementation of NHSE
      dose-banding tables. Indeed, inter-patient variability in drug clearance and
      exposure far outweighs the impact of relatively small drug dose changes
      associated with dose banding.

PMID- 29335157
TI  - Thermal and epithermal neutron flux distributions measurement in thermal column
      of TRR using an experimental-simulation method.
AB  - For designing an appropriate neutron beam, the determination of neutron flux at
      any irradiation facility is an important key factor. Due to the importance of
      determining the thermal and epithermal neutron fluxes in a typical thermal column
      of a reactor, a simple and accurate technique is introduced in this study.
      Absolute thermal and epithermal fluxes were measured experimentally at a certain
      point using the foil activation method by neutron bombardment of bare and cadmium
      covered Au foils. The relative neutron fluxes were also derived simply by means
      of Monte Carlo simulation by accurate modelling of the reactor components.
      Finally, by normalization of the relative distribution flux with regard to
      information about the absolute neutron flux, the accurate thermal and epithermal
      neutron distributions were derived, separately.

PMID- 29335156
TI  - Adapting cervical cancer screening for women vaccinated against human
      papillomavirus infections: The value of stratifying guidelines.
AB  - BACKGROUND: Several countries have implemented vaccination against human
      papillomavirus (HPV) for adolescent girls and must decide whether and how to
      adapt cervical cancer (CC) screening for these low-risk women. We aimed to
      identify the optimal screening strategies for women vaccinated against HPV
      infections and quantify the amount that could be spent to identify vaccination
      status among women and stratify CC screening guidelines accordingly. METHODS: We
      used a mathematical model reflecting HPV-induced CC in Norway to project the long
      term health benefits, resources and costs associated with 74 candidate-screening
      strategies that varied by screening test, start age and frequency. Strategies
      were considered separately for women vaccinated with the bivalent/quadrivalent
      (2/4vHPV) and nonavalent (9vHPV) vaccines. We used a cost-effectiveness framework
      (i.e. incremental cost-effectiveness ratios and net monetary benefit) and a
      commonly-cited Norwegian willingness-to-pay threshold of ?75,000 per quality
      adjusted life-year gained. RESULTS: The most cost-effective screening strategy
      for 9vHPV- and 2/4vHPV-vaccinated women involved HPV testing once and twice per
      lifetime, respectively. The value of stratifying guidelines by vaccination status
      was ?599 (2/4vHPV) and ?725 (9vHPV) per vaccinated woman. Consequently, for the
      first birth cohort of ~22,000 women who were vaccinated in adolescence in Norway,
      between ?10.5-13.2 million over their lifetime could be spent on identifying
      individual vaccination status and stratify screening while remaining cost
      effective. CONCLUSION: Less intensive strategies are required for CC screening to
      remain cost-effective in HPV-vaccinated women. Moreover, screening can remain
      cost-effective even if large investments are made to identify individual
      vaccination status and stratify screening guidelines accordingly.

PMID- 29335158
TI  - Arvanil, olvanil, AM 1172 and LY 2183240 (various cannabinoid CB1 receptor
      agonists) increase the threshold for maximal electroshock-induced seizures in
      mice.
AB  - BACKGROUND: Recent evidence reveals therapeutic potential for cannabinoids to
      reduce seizure frequency, severity and duration. Animal models are useful tools
      to determine the potential antiseizure or antiepileptic effects of cannabinoids.
      The objective of this study was evaluation of the effect of arvanil, olvanil, AM
      1172 and LY 2183240, the compounds interacted with endocannabinoid and/or
      endovanilloid systems, on convulsions in the commonly used model of convulsions
      in mice. METHODS: Arvanil and olvanil were injected intraperitoneally (ip) 30min
      and AM 1172 and LY 2183240 were administered ip 60min before the maximal
      electroshock seizure threshold (MEST) test. The criterion for convulsant activity
      was tonic hindlimb extension. RESULTS: Arvanil, olvanil, AM 1172 and LY 2183240
      dose-dependently increased the electroconvulsive threshold in mice. The TID20
      (threshold increasing dose 20) values for arvanil, olvanil, AM 1172 and LY
      2183240 were 0.9, 2.18, 2.48 and 3.56mgkg-1, respectively, and the TID50
      (threshold increasing dose 50) values were 1.88, 6.45, 6.29 and 10.04mgkg-1,
      respectively. CONCLUSION: This study identified anticonvulsant effects of
      arvanil, olvanil, AM 1172 and LY 2183240. The order of the magnitude of the
      anticonvulsant effects of the examined compounds was following:
      arvanil>olvanil>AM 1172>LY 2183240.

PMID- 29335159
TI  - Repeated Domperidone treatment modulates pulmonary cytokines in LPS-induced acute
      lung injury in mice.
AB  - The dopaminergic antagonist drug Domperidone has immunomodulatory effects. We
      investigated the effects of repeated Domperidone treatment in a model of
      Lypopolyssacharide (LPS)-induced acute lung inflammation. Adult C57BL/6J mice
      were treated with either Vehicle or Domperidone for 5days, and challenged
      intranasally with LPS in the following day. The behavior of mice was analyzed in
      the open field and elevated plus-maze test before and 24h after LPS challenge.
      The bronchoalveolar lavage fluid, blood and lung tissue were collected 24h and
      48h after LPS challenge. Domperidone treatment increased LPS-induced tumor
      necrosis factor (TNF) and interleukin (IL)-6 production in the bronchoalveolar
      lavage fluid, without altering tissue damage and the number of immune cells in
      the lungs and circulation. Locomotor and anxiety-like behavior were unchanged
      after Domperidone and/or LPS treatment. Cytokine data indicate that Domperidone
      promotes a change in activity of other cell types, likely alveolar epithelial
      cells, without affecting immune cell migration in the present model. Due to the
      role of these cytokines in progression of inflammation, Domperidone treatment may
      exacerbate a subsequent inflammatory injury.

PMID- 29335160
TI  - Mobile phone use among patients and health workers to enhance primary healthcare:
      A qualitative study in rural South Africa.
AB  - Mobile phones have the potential to improve access to healthcare information and
      services in low-resourced settings. This study investigated the use of mobile
      phones among patients with chronic diseases, pregnant women, and health workers
      to enhance primary healthcare in rural South Africa. Qualitative research was
      undertaken in Mpumalanga in 2014. Semi structured in-depth interviews were
      conducted with 113 patients and 43 health workers from seven primary healthcare
      clinics and one district hospital. Data were thematically analysed. We found that
      some health workers and patients used their own mobile phones for healthcare,
      bearing the cost themselves. Patients used their mobile phones to remind
      themselves to take medication or attend their clinic visits, and they appreciated
      receiving voice call reminders. Some patients and health workers accessed
      websites and used social media to gather health information, but lacked web
      search strategies. The use of the websites and social media was intermittent due
      to lack of financial ability to afford airtime among these patients and health
      workers. Many did not know what to search for and where to search. Doctors have
      developed their own informal mobile health solutions in response to their work
      needs and lack of resources due to their rurality. Physical and social factors
      influence the usability of mobile phones for healthcare, and this can shape
      communication patterns such as poor eyesight. The bottom-up use of mobile phones
      has been evolving to fill the gaps to augment primary care services in South
      Africa; however, barriers to access remain, such as poor digital infrastructure
      and low digital literacy.

PMID- 29335161
TI  - Health equity monitoring for healthcare quality assurance.
AB  - Population-wide health equity monitoring remains isolated from mainstream
      healthcare quality assurance. As a result, healthcare organizations remain ill
      informed about the health equity impacts of their decisions - despite becoming
      increasingly well-informed about quality of care for the average patient. We
      present a new and improved analytical approach to integrating health equity into
      mainstream healthcare quality assurance, illustrate how this approach has been
      applied in the English National Health Service, and discuss how it could be
      applied in other countries. We illustrate the approach using a key quality
      indicator that is widely used to assess how well healthcare is co-ordinated
      between primary, community and acute settings: emergency inpatient hospital
      admissions for ambulatory care sensitive chronic conditions ("potentially
      avoidable emergency admissions", for short). Whole-population data for 2015 on
      potentially avoidable emergency admissions in England were linked with
      neighborhood deprivation indices. Inequality within the populations served by 209
      clinical commissioning groups (CCGs: care purchasing organizations with mean
      population 272,000) was compared against two benchmarks - national inequality and
      inequality within ten similar populations - using neighborhood-level models to
      simulate the gap in indirectly standardized admissions between most and least
      deprived neighborhoods. The modelled inequality gap for England was 927
      potentially avoidable emergency admissions per 100,000 people, implying 263,894
      excess hospitalizations associated with inequality. Against this national
      benchmark, 17% of CCGs had significantly worse-than-benchmark equity, and 23%
      significantly better. The corresponding figures were 11% and 12% respectively
      against the similar populations benchmark. Deprivation-related inequality in
      potentially avoidable emergency admissions varies substantially between English
      CCGs serving similar populations, beyond expected statistical variation.
      Administrative data on inequality in healthcare quality within similar
      populations served by different healthcare organizations can provide useful
      information for healthcare quality assurance.

PMID- 29335162
TI  - The effectiveness of virtual simulation in improving student nurses' knowledge
      and performance during patient deterioration: A pre and post test design.
AB  - BACKGROUND: Preparing nursing students to perform competently in complex
      emergency situations, such as during rapid patient deterioration, is challenging.
      Students' active engagement in such scenarios cannot be ensured, due to the
      unexpected nature of such infrequent events. Many students may consequently not
      experience and integrate the management of patient deterioration into their
      knowledge and practical competency by the end of their studies, making them
      unprepared to manage such situations as practicing nurses. This study
      investigated the effectiveness of virtual simulation in improving performance
      during rapid patient deterioration. OBJECTIVE: To investigate the effectiveness
      of virtual simulation in improving student nurses' knowledge and performance
      during rapid patient deterioration. DESIGN: A pre- and post-test design was used.
      SETTING: Nursing students at a university in Malta were invited to participate in
      a virtual simulation program named FIRST2ACTWebTM, using their own computer
      devices. PARTICIPANTS: A total of 166 (response rate=50%) second and third year
      diploma and degree nursing students participated in the study. METHODS: The
      simulation included three scenarios (Cardiac-Shock-Respiratory) portraying
      deteriorating patients. Performance feedback was provided at the end of each
      scenario. Students completed pre- and post-scenario knowledge tests and
      performance during each scenario was recorded automatically on a database.
      RESULTS: Findings showed a significant improvement in the students' post-scenario
      knowledge (z=-6.506, p<0.001). Highest mean performance scores were obtained in
      the last scenario (M=19.7, median: 20.0, s.d. 3.41) indicating a learning effect.
      Knowledge was not a predictor of students' performance in the scenarios.
      CONCLUSIONS: This study supports virtual simulation as an effective learning tool
      for pre-registration nursing students in different programs. Simulation improves
      both knowledge about and performance during patient deterioration. Virtual
      simulation of rare events should be a key component of undergraduate nurse
      education, to prepare students to manage complex situations as practicing nurses.

PMID- 29335163
TI  - N,N-Diethylmethylamine as lineshape standard for NMR above 130 K.
AB  - We demonstrate that N,N-Diethylmethylamine (DEMA) is a useful compound for
      shimming the magnetic field when doing NMR experiments at room temperature and
      130 K, near the temperature used in many dynamic nuclear polarization (DNP)
      experiments. The resonance assigned to the N-methyl carbon in DEMA at 14.7 T and
      140 K has a full-width-half-max linewidth of <4 Hz and has a spin-lattice
      relaxation time of 0.17 +/- 0.03 s.

PMID- 29335164
TI  - Local T1-T2 distribution measurements in porous media.
AB  - A novel slice-selective T1-T2 measurement is proposed to measure spatially
      resolved T1-T2 distributions. An adiabatic inversion pulse is employed for slice
      selection. The slice-selective pulse is able to select a quasi-rectangular slice,
      on the order of 1 mm, at an arbitrary position within the sample.The method does
      not employ conventional selective excitation in which selective excitation is
      often accomplished by rotation of the longitudinal magnetization in the slice of
      interest into the transverse plane, but rather a subtraction based on CPMG data
      acquired with and without adiabatic inversion slice selection. T1 weighting is
      introduced during recovery from the inversion associated with slice selection.
      The local T1-T2 distributions measured are of similar quality to bulk T1-T2
      measurements. The new method can be employed to characterize oil-water mixtures
      and other fluids in porous media. The method is beneficial when a coarse spatial
      distribution of the components is of interest.

PMID- 29335165
TI  - Dioxins, furans and dioxin-like PCBs in sediment samples and suspended
      particulate matter from the Scheldt estuary and the North Sea Coast: Comparison
      of CALUX concentration levels in historical and recent samples.
AB  - BACKGROUND: The Scheldt estuary is historically a highly polluted river system.
      While several studies have focused on contamination with metals, pesticides,
      Polycyclic Aromatic Hydrocarbons (PAHs) and marker PolyChlorinated Biphenyls
      (PCBs), no data are available concerning past contamination by dioxin-like
      compounds. OBJECTIVES: The objective of this study is to determine spatial and
      time trends of PolyChlorinated Dibenzo-p-Dioxins and DibenzoFurans (PCDD/Fs) and
      dioxin-like PCBs (dl-PCBs) in sediment samples and Suspended Particulate Matter
      (SPM) from the Scheldt River basin and the North Sea Coast. METHODS: Dioxin-like
      compounds (PCDD/F and dl-PCB fractions) were measured with the CALUX-bioassay.
      Bioanalytical EQuivalent concentrations (BEQs) and Total Organic Carbon (TOC)
      content of historical (1982-1984) and recent (2011-2015) sediment and SPM samples
      from different locations in the coastal area and the estuary, were evaluated.
      RESULTS: A decrease in dioxin-like compound concentrations was found at all
      stations over time, especially for the PCDD/Fs. Dl-PCBs were relatively low in
      all samples. The Scheldt mouth and the Antwerp harbor yielded the highest BEQs
      and levels were higher in SPM than in sediment due to the higher organic carbon
      content in this fraction. CONCLUSIONS: Current PCDD/F and dl-PCB levels in the
      Belgian Coastal Zone and Scheldt estuary are much lower than their levels 30
      years ago and pose a relatively low risk to the aquatic system. This is the
      result of a strong decrease in emissions, however, large local variabilities in
      sediment concentration levels can still exist because of local variability in
      sedimentation, erosion rates and in organic carbon content.

PMID- 29335166
TI  - Ambient soil cation exchange capacity inversely associates with infectious and
      parasitic disease risk in regional Australia.
AB  - Human contact with soil may be important for building and maintaining normal
      healthy immune defence mechanisms, however this idea remains untested at the
      population-level. In this continent-wide, cross-sectional study we examine the
      possible public health benefit of ambient exposures to soil of high cation
      exchange capacity (CEC), a surrogate for potential immunomodulatory soil
      microbial diversity. We compare distributions of normalized mean 2011/12-2012/13
      age-standardized public hospital admission rates (cumulative incidence) for
      infectious and parasitic diseases across regional Australia (representing an
      average of 29,516 patients/year in 228 local government areas), within tertiles
      of socioeconomic status and soil exposure. To test the significance of soil CEC,
      we use probabilistic individual-level environmental exposure data (with or
      without soil), and group-level variables, in robust non-parametric multilevel
      modelling to predict disease rates in unseen groups. Our results show that in
      socioeconomically-deprived areas with high CEC soils, rates of infectious and
      parasitic disease are significantly lower than areas with low CEC soils. Also,
      health inequality (relative risk) due to socioeconomic status is significantly
      lower in areas with high CEC soils compared to low CEC soils (Delta relative risk
      = 0.47; 95% CI: 0.13, 0.82). Including soil exposure when modelling rates of
      infectious and parasitic disease significantly improves prediction performance,
      explaining an additional 7.5% (Delta r2 = 0.075; 95% CI: 0.05, 0.10) of variation
      in disease risk, in local government areas that were not used for model building.
      Our findings suggest that exposure to high CEC soils (typically high soil
      biodiversity) associates with reduced risk of infectious and parasitic diseases,
      particularly in lower socioeconomic areas.

PMID- 29335167
TI  - Fate and hazard of the electrochemical oxidation of triclosan. Evaluation of
      polychlorodibenzo-p-dioxins and polychlorodibenzofurans (PCDD/Fs) formation.
AB  - Triclosan (TCS) is widely used as antiseptic or preservative in many personal
      care products (PCPs), such as cosmetics, hand wash, toothpaste and deodorant
      soaps, among others. It is characterized by acute toxicity, resistance to
      biodegradation, environmental persistence and relatively high lipophilicity. In
      order to protect the environment and natural resources from the negative effects
      of the discharge of polluted wastewater with TCS, the application of efficient
      remediation technologies able to degrade the pollutant to harmless levels becomes
      crucial. Electrochemical oxidation, among all advanced oxidation processes
      (AOPs), has been reported as very effective in the complete degradation of a
      number of persistent pollutants; therefore, its performance using boron-doped
      diamond (BDD) anodes, and response to operation variables, has been studied in
      this work. As expected, complete degradation of TCS was achieved in all the
      studied conditions; however, going a step further and knowing that TCS is a
      precursor of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), their
      quantitative presence in the oxidation media has been assessed. Results showed
      the dominance of dichlorinated (DCDD) and trichlorinated (TrCDD/Fs) in the
      homologue profile of total PCDD/Fs, reaching values up to 1.48 * 105 pg L-1 in
      samples with initial concentration of TCS of 100 mg L-1 and NaCl as electrolyte.
      Under these conditions, the International Toxicity Equivalency Factor (I-TEF)
      achieved values up to 2.76 * 102 pg L-1. Nevertheless, the presence of copper in
      the oxidation medium tends to reduce I-TEF values. Finally, considering the
      information reported in literature, a mechanism describing the formation of low
      chlorinated PCDD/Fs from TCS oxidation reactions is proposed.

PMID- 29335168
TI  - WRF modeling of PM2.5 remediation by SALSCS and its clean air flow over Beijing
      terrain.
AB  - Atmospheric simulations were carried out over the terrain of entire Beijing,
      China, to investigate the effectiveness of an air-pollution cleaning system named
      Solar-Assisted Large-Scale Cleaning System (SALSCS) for PM2.5 mitigation by using
      the Weather Research and Forecasting (WRF) model. SALSCS was proposed to utilize
      solar energy to generate airflow therefrom the airborne particulate pollution of
      atmosphere was separated by filtration elements. Our model used a derived
      tendency term in the potential temperature equation to simulate the buoyancy
      effect of SALSCS created with solar radiation on its nearby atmosphere. PM2.5
      pollutant and SALSCS clean air were simulated in the model domain by passive
      tracer scalars. Simulation conditions with two system flow rates of 2.64 * 105
      m3/s and 3.80 * 105 m3/s were tested for seven air pollution episodes of Beijing
      during the winters of 2015-2017. The numerical results showed that with eight
      SALSCSs installed along the 6th Ring Road of the city, 11.2% and 14.6% of PM2.5
      concentrations were reduced under the two flow-rate simulation conditions,
      respectively.

PMID- 29335169
TI  - Seasonal variations in fine particle composition from Beijing prompt oxidative
      stress response in mouse lung and liver.
AB  - Exposure to air pollution can induce oxidative stress, inflammation and adverse
      health effects. To understand how seasonal and chemical variations drive health
      impacts, we investigated indications for oxidative stress and inflammation in
      mice exposed to water and organic extracts from urban fine particles/PM2.5
      (particles with aerodynamic diameter <= 2.5 MUm) collected in Beijing, China.
      Higher levels of pollution components were detected in heating season (HS, winter
      and part of spring) PM2.5 than in the non-heating season (NHS, summer and part of
      spring and autumn) PM2.5. HS samples were high in metals for the water extraction
      and high in polycyclic aromatic hydrocarbons (PAHs) for the organic extraction
      compared to their controls. An increased inflammatory response was detected in
      the lung and liver following exposure to the organic extracts compared to the
      water extracts, and mostly in the HS PM2.5. While reduced antioxidant response
      was observed in the lung, it was activated in the liver, again, more in the HS
      extracts. Nrf2 transcription factor, a master regulator of stress response that
      controls the basal oxidative capacity and induces the expression of antioxidant
      response, and its related genes were induced. In the liver, elevated levels of
      lipid peroxidation adducts were measured, correlated with histologic analysis
      that revealed morphologic features of cell damage and proliferation, indicating
      oxidative and toxic damage. In addition, expression of genes related to
      detoxification of PAHs was observed. Altogether, the study suggests that the
      acute effects of PM2.5 can vary seasonally with stronger health effects in the HS
      than in the NHS in Beijing, China and that some secondary organs may be
      susceptible for the exposure damage. Specifically, the liver is a potential organ
      influenced by exposure to organic components such as PAHs from coal or biomass
      burning and heating.

PMID- 29335170
TI  - Risk factors associated with rural water supply failure: A 30-year retrospective
      study of handpumps on the south coast of Kenya.
AB  - An improved understanding of failure risks for water supplies in rural sub
      Saharan Africa will be critical to achieving the global goal of safe water for
      all by 2030. In the absence of longitudinal biophysical and operational data,
      investigations into water point failure risk factors have to date been limited to
      cross-sectional research designs. This retrospective cohort study applies
      survival analysis to identify factors that predict failure risks for handpumps
      installed on boreholes along the south coast of Kenya from the 1980s. The
      analysis is based on a unique dataset linking attributes of >300 water points at
      the time of installation with their operational lifespan over the following
      decades. Cox proportional hazards and accelerated failure time models suggest
      water point failure risks are higher and lifespans are shorter when water
      supplied is more saline, static water level is deeper, and groundwater is pumped
      from an unconsolidated sand aquifer. The risk of failure also appears to grow as
      distance to spare part suppliers increases. To bolster the sustainability of
      rural water services and ensure no community is left behind, post-construction
      support mechanisms will need to mitigate heterogeneous environmental and
      geographical challenges. Further studies are needed to better understand the
      causal pathways that underlie these risk factors in order to inform policies and
      practices that ensure water services are sustained even where unfavourable
      conditions prevail.

PMID- 29335172
TI  - Preparation of amidoxime-functionalized mesoporous silica nanospheres (ami-MSN)
      from coal fly ash for the removal of U(VI).
AB  - It is usually difficult to control the microstructure of mesoporous silica
      materials using coal fly ash as raw materials. In this study, amidoxime
      functionalized mesoporous silica nanospheres (ami-MSN) were prepared from coal
      fly ash using a novel interfacial cohydrolysis-condensation method in an alkane
      aqueous system. Characterizations suggested a regular microstructure, high
      specific surface area (676 m2/g) as well as stable and uniformly distributed
      amidoxime groups in the ami-MSN framework. Furthermore, ami-MSN displays a high
      U(VI) removal capacity in sorption experiments (98.9% removal efficiency of 50
      ppm U(VI) at a dosage of 600 mg/L). The sorption showed significant pH
      dependence. Introducing various cations and anions showed differing effects on
      sorption, which can be attributed to differing complexation abilities of ions/ami
      MSN/U(VI). The sorption mechanism was also studied. In pursuit of the strategy of
      "treating wastewater with materials derived from waste," this work suggests that
      ami-MSN can be an effective and low-cost sorbent for U(VI) removal.

PMID- 29335171
TI  - Effect of hydrogen peroxide on Microcystic aeruginosa: Role of cytochromes P450.
AB  - Cyanobacterial bloom has been rising as a worldwide issue owing to its adverse
      effects to water quality and ecological health. To solve this problem, hydrogen
      peroxide (H2O2) has been considered as a potential algaecide because no by
      products are generated after treatment and because it kills cyanobacteria
      selectively. In addition, cytochromes P450 (CYPs) was reported to be related with
      H2O2, but the roles of CYPs in the regulation of H2O2 in cyanobacteria have yet
      to be investigated. In this study, the CYPs suicide inhibitor 1
      aminobenzotriazole (ABT) was added to the representative cyanobacteria
      Microcystis aeruginosa (M. aeruginosa) exposed to H2O2. The results showed that
      CYPs mediates the effects of H2O2 on M. aeruginosa. To be exact, the addition of
      ABT induced greater inhibitory effects on the growth and higher reactive oxygen
      species levels in M. aeruginosa comparing to those treated with H2O2 alone. At
      the same time, photosynthetic parameters significantly decreased, and the content
      of extracellular microcystins (MCs) increased but the total MCs decreased due to
      the combined effect of H2O2 and ABT. ABT also intensified the aggregation of Fe,
      which might explain the effects on photosynthesis and synthesis of MCs.
      Furthermore, the transcriptional levels of MCs-synthesis genes (mcyA and mcyD)
      decreased but MCs-release gene (mcyH) increased, and photosynthetic genes (psaB,
      psbD1 and rbcL) decreased, which confirmed the effects on the MC
      production/release and electron transport of photosynthesis, respectively. In
      summary, this study illuminated the mediation role of CYPs in the adverse effects
      on M. aeruginosa induced by H2O2, thus providing new theoretical basis for the
      explanation of H2O2 as potential algaecide.

PMID- 29335173
TI  - Application of Fe3O4@MIL-100 (Fe) core-shell magnetic microspheres for evaluating
      the sorption of organophosphate esters to dissolved organic matter (DOM).
AB  - Organophosphate esters (OPEs) are widely used as flame retardants and
      plasticizers in many products and materials. Because of the potential biologic
      toxicity on human beings, OPEs are regarded as a class of emerging pollutants.
      Dissolved organic matters (DOM) have significant effects on the bioavailability
      and toxicity of the pollutants in the environment. Negligible-depletion solid
      phase microextraction (nd-SPME) is an efficient way for measuring the freely
      dissolved pollutants but suffers from long equilibrium time. Metal-organic
      frameworks (MOFs) are a class of porous crystalline materials with unique
      properties such as high pore volume, regular porosity, and tunable pore size,
      being widely used for the extraction of various organic compounds. Here we
      developed a novel method for quick determination the sorption coefficients of
      OPEs to DOM in aquatic phase using Fe3O4@MIL-100 (Fe) core-shell magnetic
      microspheres. The mesoporous structures of the as-synthesized microspheres
      hindered the extraction of OPEs which associated with humic acid due to the
      volume exclusion effect. However, the freely dissolved OPEs can access into the
      mesoporous and then were extracted by MIL-100 (Fe). Due to the small pore size
      (4.81 nm), large surface area (141 m2 g-1), high pore volume (0.17 g3 g-1), and
      ultra-thin MOFs layers, Fe3O4@MIL-100 (Fe) core-shell magnetic microspheres have
      large contact area for the analytes in aqueous phase and therefore the diffusion
      distance was largely shortened. Besides, the microspheres can be collected
      conveniently after the extraction process by applying a magnetic field. Compared
      to the nd-SPME method with 35 h equilibration time (t90%), the proposed method
      for these studied OPEs only need 24 min to achieve equilibration. The sorption
      coefficients (logKDOC) of the OPEs to humic acid were ranged from 3.84-5.28,
      which were highly consistent with the results by using polyacrylate-coated fiber
      and polydimethylsiloxane-coated fiber with nd-SPME.

PMID- 29335174
TI  - Testing association between soil bacterial diversity and soil carbon storage on
      the Loess Plateau.
AB  - Bacteria are widely distributed and play an important role in soil carbon (C)
      cycling. The impact of soil bacterial diversity on soil C storage has been well
      established, yet little is known about the underlying mechanisms and the
      interactions among them. Here, we examined the association between soil bacterial
      diversity and soil C storage in relation to vegetation restoration on the Loess
      Plateau. The dominant phyla among land use types (artificial forest, Af; natural
      shrubland, Ns; artificial grassland, Ag; natural grassland, Ng; slope cropland,
      Sc) were Acidobacteria, Actinobacteria, Alphaproteobacteria, and
      Betaproteobacteria, which transited from Acidobacteria-dominant to Actinobacteria
      dominant community due to vegetation restoration. Soil C storage and the Shannon
      diversity index of soil bacterial community (HBacteria) showed the order Ns > Ng
      > Af > Ag > Sc, whereas no significant difference was found in Good's coverage (p
      > .05). Further, a strong relationship was observed between the relative
      abundance of dominant bacterial groups and soil C storage (p < .05).
      Additionally, soil bacterial diversity was closely related to soil C storage
      based on the structural equation model (SEM) and generalized additive models
      (GAMs). Specifically, soil C storage had the largest deterministic effects,
      explaining >70% of the variation and suggesting a strong association between soil
      C storage and soil bacterial diversity. Overall, we propose that further studies
      are necessary with a focus on the soil bacterial groups with specific functions
      in relation to soil C storage on the Loess Plateau.

PMID- 29335175
TI  - An assessment of the Ca weathering sources to surface waters on the Precambrian
      Shield in central Ontario.
AB  - There is increasing concern over the negative ecological impacts caused by
      falling calcium (Ca) concentrations in lakes, particularly in central Ontario,
      Canada. Forecasting regional changes in lake Ca concentrations relies on accurate
      estimates of mineral weathering rates that are not widely available. In this
      study, bulk atmospheric deposition, surface water and soil chemistry along with
      87Sr/86Sr isotope measurements were used to provide regional insight into
      weathering controls on Ca concentrations in lakes. Regionally, Ca concentrations
      in 90% of 129 lakes sampled in central Ontario were <0.1 mmol L-1 and the Ca/Sr
      ratio in lakes increased and the K/Sr ratio decreased with increasing Sr
      concentration, which is indicative of greater Ca sources from calcite or apatite
      in the higher Ca lakes. Significant relationships between 87Sr/86Sr ratios and
      Ca/Sr rations in dilute acid (0.1 M HCl) soil extracts are also indicative of the
      presence of trace amounts of calcite or apatite in surficial soils. Within the
      low (<0.7 mmol L-1) Ca lakes, defined in this study that are considered most at
      risk from falling Ca concentrations, 87Sr/86Sr ratios fell within the range
      observed in weak acid soil extracts and were also significantly related to Ca/Na
      and K/Sr ratios in surface waters. There were large inconsistencies however,
      between Ca/Na ratios and Ca/Sr in surface waters and soil acid extracts that
      suggest differences in 87Sr/86Sr ratios in surface waters of the low Ca lakes do
      not simply reflect differences in Ca derived from non-silicate minerals in
      surficial soils and that that Ca sources from deeper soil or bedrock are also
      important contributors to surface water Ca in these low Ca lakes.

PMID- 29335176
TI  - Arsenic characteristics in the terrestrial environment in the vicinity of the
      Shimen realgar mine, China.
AB  - In this study, multiple types of samples, including soils, plants, litter and
      soil invertebrates, were collected from a former arsenic (As) mine in China. The
      total As concentrations in the soils, earthworms, litter and the aboveground
      portions of grass from the contaminated area followed the decreasing order of 83
      2224 mg/kg, 31-430 mg/kg, 1-62 mg/kg and 2-23 mg/kg, respectively. X-ray
      absorption near-edge structure (XANES) analysis revealed that the predominant
      form of As in the soils was arsenate (As(V)), while no arsenite (As(III)) was
      detected. In the grass and litter of the native plant community, inorganic As
      species (As(V) and As(III)) were the main species, while minor amounts of DMA,
      MMA, AsC, and an unknown As species were also detected in the extracts analyzed
      with high-performance liquid chromatography inductively coupled plasma mass
      spectrometry (HPLC-ICP-MS). The As speciation and As concentrations varied with
      the plant species, and very high As levels (197-584 mg/kg) and proportions of
      inorganic As (>99%) were found in two As-hyperaccumulating ferns, Pteris vittata
      and Pteris cretica. The major As species extracted from earthworms were
      inorganic, with proportions of 51-53% As(III) and 38-48% As(V). AsB was the only
      organic species present in the earthworm samples, although at low proportions
      (<8.99%). The internal bioconversion of other As species is hypothesized to
      contribute greatly to the formation and accumulation of AsB in earthworms,
      although the direct external absorption of organic As from soils might be another
      source. This study sheds light on the potential sources of complex
      organoarsenicals, such as AsB, in terrestrial organisms.

PMID- 29335177
TI  - Study of the evolution of gravel beaches nourished with sand.
AB  - Coastal erosion is a worldwide problem, so accurate knowledge of the factors
      involved in the shoreline evolution is of great importance. This study analysed
      three gravel beaches that were nourished with sand from the same source. However,
      the evolution of their shoreline was different in each case. For its analysis,
      different factors were studied such as the shoreline and cross-shore profile
      evolution, the maritime climate, sedimentology and mineralogy. From the results,
      it should be noted that Centro beach is the most stable with a loss of surface
      after the first regeneration of 12.8%, while Carrer de mar is the most instable
      with a loss of 20.9%. The Posidonia oceanica meadow is one of the factors that
      make Centro beach the most stable despite being the one that receives the most
      wave energy. Another factor is its mineralogy and more specifically the
      composition of the particles that form the sample. Thus, it is observed how the
      cracking or the formation of particles by different minerals with a fragile
      union, are factors that make the beaches behave differently against erosion. For
      this reason, it is concluded that in order for the shoreline to be as stable as
      possible over time, a previous study of the sediment to be used for nourishment
      is necessary, as well as its possible effect on the ecosystem, since the future
      shoreline evolution will depend on it.

PMID- 29335178
TI  - Bone lead levels in an environmentally exposed elderly population in shanghai,
      China.
AB  - This study looked at measurements of lead (Pb) in a pilot population of
      environmentally exposed elderly residents of Shanghai, China and presented the
      first set of bone Pb data on an elderly Chinese population. We found that with
      environmental exposures in this population using K-shell x-ray fluorescence
      (KXRF) bone Pb measurements 40% of the individuals had bone Pb levels above the
      nominal detection limit with an average bone lead level of 4.9 +/- 3.6 MUg/g.
      This bone lead level is lower than comparable values from previous studies of
      community dwelling adults in US cities. This population had a slightly higher
      geometric mean blood Pb of 2.6 MUg/dL than the adult US population. The main
      conclusion of this data is that in Shanghai there is environmental exposure to
      Pb, measured through blood and bone, which should be further investigated to
      assess the health impact of this exposure.

PMID- 29335179
TI  - Chronic nitrogen addition induces a cascade of plant community responses with
      both seasonal and progressive dynamics.
AB  - Short-lived herbaceous plants provide a useful model to rapidly reveal how
      multiple generations of plants in natural plant communities of sensitive desert
      ecosystems will be affected by N deposition. We monitored dynamic responses of
      community structure, richness, evenness, density and biomass of herbaceous plants
      to experimental N addition (2:1 NH4+:NO3- added at 0, 0.5, 1, 3, 6 and 24gNm-2a
      1) in three seasons in each of three years in the Gurbantunggut desert, a typical
      temperate desert of central Asia. We found clear rate-dependent and season
      dependent effects of N deposition on each of these variables, in most cases
      becoming more obvious through time. N addition reduced plant richness, leading to
      a loss of about half of the species after three generations in the highest N
      application level. Evenness and density were relatively insensitive to all but
      the greatest levels of N addition for two generations, but negative effects
      emerged in the third generation. Biomass, both above and below ground, was non
      linearly affected by N deposition. Low and intermediate levels of N deposition
      often increased biomass, whereas the highest level suppressed biomass.
      Stimulatory effects of intermediate N addition disappeared in the third
      generation. All of these responses are strongly interrelated in a cascade of
      changes. Notably, changes in biomass due to N deposition were mediated by
      declines in richness and evenness, and other changes in community structure,
      rather than solely being the direct outcome of release from limitation. The
      interrelationships between N deposition and the different plant community
      attributes change not only seasonally, but also progressively change through
      time. These temporal changes appear to be largely independent of interannual or
      seasonal climatic conditions.

PMID- 29335180
TI  - Synthesis of nanometer-sized fayalite and magnesium-iron(II) mixture olivines.
AB  - Olivines are divalent orthosilicates with important geologic, biological, and
      industrial significance and are typically comprised of mixtures of Mg2+ and Fe2+
      ranging from forsterite (Mg2SiO4) to fayalite (Fe2SiO4). Investigating the role
      of Fe(II) in olivine reactivity requires the ability to synthesize olivines that
      are nanometer-sized, have different percentages of Mg2+ and Fe2+, and have good
      bulk and surface purity. This article demonstrates a new method for synthesizing
      nanosized fayalite and Mg-Fe mixture olivines.First, carbonaceous precursors are
      generated from sucrose, PVA, colloidal silica, Mg2+, and Fe3+. Second, these
      precursors are calcined in air to burn carbon and create mixtures of Fe(III)
      oxides, forsterite, and SiO2. Finally, calcination in reducing CO-CO2 gas buffer
      leads to Fe(II)-rich olivines. XRD, Mossbauer, and IR analyses verify good bulk
      purity and composition. XPS indicates that surface iron is in its reduced Fe(II)
      form, and surface Si is consistent with olivine. SEM shows particle sizes
      predominately between 50 and 450 nm, and BET surface areas are 2.8-4.2 m2/g. STEM
      HAADF analysis demonstrates even distributions of Mg and Fe among the available
      M1 and M2 sites of the olivine crystals. These nanosized Fe(II)-rich olivines are
      suitable for laboratory studies with in situ probes that require mineral samples
      with high reactivity at short timescales.

PMID- 29335181
TI  - Enhancing the photovoltaic performance of bulk heterojunction polymer solar cells
      by adding Rhodamine B laser dye as co-sensitizer.
AB  - Ternary blend (TB) strategy has been considered as an effective method to enhance
      the photovoltaic performance of bulk heterojunction (BHJ) polymer solar cells
      (PSCs). Here, we report on TB-based PSCs containing two donor materials; poly-3
      hexylthiophene (P3HT) and Rhodamine B (RhB) laser organic dye, and [6,6]-phenyl
      C61 butyric acid methyl ester (PC61BM) as an acceptor. The influence of RhB
      weight percentage and injection volume was extensively studied. To gain insight
      into the influences of RhB on the photovoltaic performance of PSCs,
      physicochemical and optical properties of TBs were compared with those of BHJ
      binary blend as a standard. RhB broadened the light absorption properties of the
      active layer and played a bridging role between P3HT and PC61BM. The PCE and
      short-circuit current density (Jsc) of the optimized TB-based PSCs comprising of
      0.5 wt% RhB reached 5% and 12.12 mA/cm2, respectively. Compared to BHJ standard
      cell, the PCE and the generated current was improved by two orders of magnitude
      due to higher photon harvest of the active layer, cascade energy level structure
      of TB components and a considerable decrease in the charge carrier recombination.
      The results suggest that RhB can be considered as an effective material for
      application in PSCs to attain high photovoltaic performance.

PMID- 29335182
TI  - Microstructures and performances of pegylated polysulfone membranes from an in
      situ synthesized solution via vapor induced phase separation approach.
AB  - In situ pegylated (PEGylated) microporous membranes have been extensively
      reported using poly(ethylene glycol) (PEG)-based polymers as blending additives.
      Alternatively, free standing PEGylated polysulfone (PSf) membranes with excellent
      hydrophilicity and antifouling ability were directly fabricated from
      polysulfone/poly(ethylene glycol) methyl ether methacrylate (PSf/PEGMA) solutions
      after in situ cross-linking polymerization without any treatment via vapor
      induced phase separation (VIPS) process for the first time. The microstructures
      and performances of the resulting membranes shifted regularly by adjusting
      exposure time of the liquid film in humid air. With increasing exposure time,
      plenty of worm-like networks formed and distributed on membrane surfaces,
      meanwhile cross-sectional morphology changed from asymmetric finger-like
      microporous structure to symmetric cellular-like structure, resulting in better
      mechanical stability. As the exposure time raised from 0 to 5 min, the surface
      coverage of carboxyl groups increased from ~1.1 to 4.0 mol%, leading to the
      decrease in water contact angle from ~63 to 27 degrees  and the increase in water
      flux from ~110 to 512 L m-2 h-1. In addition, at prolonged exposure time,
      increasing hydrophilic PEG chains migrated to membrane surfaced and repelled the
      adsorption and deposition of protein, resulting in better antifouling ability.
      The findings of this study offer a facile and high efficient strategy for
      flexible design and fabrication of the in situ PEGylated membranes with desirable
      structures and performances in large scale.

PMID- 29335183
TI  - Microwave-assisted synthesis of palladium nanoparticles intercalated nitrogen
      doped reduced graphene oxide and their electrocatalytic activity for direct
      ethanol fuel cells.
AB  - Palladium nanoparticles decorated reduced graphene oxide (Pd-rGO) and palladium
      nanoparticles intercalated inside nitrogen doped reduced graphene oxide (Pd-NrGO)
      hybrids have been synthesized by applying a very simple, fast and economic route
      using microwave-assisted in-situ reduction and exfoliation method. The Pd-NrGO
      hybrids materials show good activity as catalyst for ethanol electro oxidation
      for direct ethanol fuel cells (DEFCs) as compared to Pd-rGO hybrids. The enhanced
      direct ethanol fuel cell can serve as alternative to fossil fuels because it is
      renewable and environmentally-friendly with a high energy conversion efficiency
      and low pollutant emission. As proof of concept, the electrocatalytic activity of
      Pd-NrGO hybrid material was accessed by cyclic voltammetry in presence of ethanol
      to evaluate its applicability in direct-ethanol fuel cells (DEFCs). The Pd-NrGO
      catalyst presented higher electro active surface area (~6.3 m2 g-1) for ethanol
      electro-oxidation when compared to Pd-rGO hybrids (~3.7 m2 g-1). Despite the
      smaller catalytic activity of Pd-NrGO, which was attributed to the lower
      exfoliation rate of this material in relation to the Pd-rGO, Pd-NrGO showed to be
      very promising and its catalytic activity can be further improved by tuning the
      synthesis parameters to increase the exfoliation rate.

PMID- 29335184
TI  - Trimellitated sugarcane bagasse: A versatile adsorbent for removal of cationic
      dyes from aqueous solution. Part I: Batch adsorption in a monocomponent system.
AB  - Trimellitated-sugarcane bagasse (STA) was used as an environmentally friendly
      adsorbent for removal of the basic dyes auramine-O (AO) and safranin-T (ST) from
      aqueous solutions at pH 4.5 and 7.0. Dye adsorption was evaluated as a function
      of STA dosage, agitation speed, solution pH, contact time, and initial dye
      concentration. Pseudo-first- and pseudo-second-order, Elovich, intraparticle
      diffusion, and Boyd models were used to model adsorption kinetics. Langmuir,
      Dubinin-Radushkevich, Redlich-Peterson, Sips, Hill-de Boer, and Fowler-Guggenheim
      models were used to model adsorption isotherms, while a Scatchard plot was used
      to evaluate the existence of different adsorption sites. Maximum adsorption
      capacities for removal of AO and ST were 1.005 and 0.638 mmol g-1 at pH 4.5, and
      1.734 and 1.230 mmol g-1 at pH 7.0, respectively. Adsorption enthalpy changes
      obtained by isothermal titration calorimetry (ITC) ranged from -21.07 +/- 0.25 to
      -7.19 +/- 0.05 kJ mol-1, indicating that both dyes interacted with STA by
      physisorption. Dye desorption efficiencies ranged from 41 to 51%, and re
      adsorption efficiencies ranged from 66 to 87%, showing that STA can be reused in
      new adsorption cycles. ITC data combined with isotherm studies allowed
      clarification of adsorption interactions.

PMID- 29335185
TI  - One step electrochemical route to the fabrication of highly ordered array of
      cylindrical nano porous structure and its electrocatalytic performance toward
      efficient hydrogen evolution.
AB  - An efficient and non-precious metal catalyst is a key factor for hydrogen
      evolution reaction (HER). Here we report that the fabrication of highly ordered
      porous arrays of Cu-Zn-Ni alloy has been carried out in a one-step
      electrochemical route at a constant apparent current density of -3 A.cm-2. The
      optimum film composition and reactivity of the electrodes for catalytic hydrogen
      evolution reaction were analyzed by using different current densities, deposition
      time and bath concentration. For this purpose, onset potentials in linear sweep
      voltammograms (LSV) were compared. The structure and morphology of nanoporous Cu
      Zn-Ni and Cu-Zn alloy were characterized by SEM and energy dispersive X-ray (EDS)
      analysis. The experimental results on the behavior of electrocatalytic activity
      of prepared alloys showed that the addition of nickel to the alloys improves of
      the electrocatalytic performance of the electrodes toward HER. In addition,
      enhancement of electrochemical activity toward hydrogen evolution can be
      attributed to the large electrochemical active surface area and porous structure
      of Cu-Zn-Ni alloy. In order to improvement of reaction kinetics, Tafel plots were
      derived from LSV voltammograms, and the exchange current densities for HER on
      synthesized electrodes (Cu-Zn and Cu-Zn-Ni alloys) were calculated about 3.2 * 10
      5 and 2.1 * 10-3 mA.cm-2, respectively.

PMID- 29335186
TI  - Rheological and calorimetric study of alkyltrimethylammonium bromide-sodium
      salicylate wormlike micelles in aqueous binary systems.
AB  - HYPOTHESIS: It is known that additives like glycerol and sucrose lead to the
      swelling of aqueous bilayer Lalpha phases. The swelling of the Lalpha phases can
      be explained by the increase of the refractive index of the mixed solvent, which
      lowers the van der Waals attraction between the bilayers. Afterwards, the
      undulation forces between the bilayers can push them apart. This hypothesis was
      previously extended to wormlike micelles (WLM) of cetyltrimethylammonium bromide
      (CTAB) and sodium salicylate (NaSal). These types of self-assembly structures
      have viscoelastic properties, and the zero shear viscosity of these solutions is
      dependent on the molar ratio NaSal/CTAB, R. At R = 0.6, R = 1.0 and R ~ 2.6 the
      viscosity goes, respectively, through a maximum, a minimum and another maximum.
      These viscosities can be explained by differences in relaxation mechanisms
      predominant in each region. Similarly to what is observed to bilayer Lalpha
      phases, the additives would change the interaction between the WLM, affecting the
      relaxation processes of each region, altering the profile from two maxima and one
      minimum to a single maximum in viscosity. In the present manuscript, it is
      investigated whether it is only the refractive index, other solvent properties,
      or a combination of several factors that induce these changes in WLM. For this,
      several additives, forming binary mixtures with water, were studied, through
      rheology of CTAB/NaSal and calorimetry of tetradecyltrimethylammonium bromide
      (TTAB)/NaSal. EXPERIMENTS: Herein, we present the zero-shear viscosity diagrams
      of NaSal and CTAB with glycerol, sucrose, dimethyl sulfoxide, 1,3-butanediol and
      urea combined with water. Additionally, isothermal titration calorimetry was used
      to obtain the variations of enthalpy for formation of WLM of TTAB and NaSal in
      mixtures of water and such additives. FINDINGS: Based on our data, only the
      refractive index match is not enough to explain the rheological and calorimetric
      behaviors of the WLM. For instance, sucrose has little effect on the micelles,
      even at the same refractive index match conditions. Additional characteristics,
      such as dielectric constant, the cohesivity of the solvent (here symbolized by
      the Gordon parameter), and the interactions of the additive with the micelles,
      have to be considered to better describe the results.

PMID- 29335187
TI  - Novel low-fouling membranes from lab to pilot application in textile wastewater
      treatment.
AB  - A novel antifouling coating based on the polymerization of a polymerisable
      bicontinuous microemulsion (PBM) was developed and applied for commercially
      available membranes for textile wastewater treatment. PBM coating was produced by
      polymerizing, on a polyethersulfone (PES) membrane, a bicontinuous microemulsion,
      realized by finely tuning its properties in terms of chemical composition and
      polymerization temperature. In particular, the PBM was prepared by using, as the
      surfactant component, inexpensive and commercially available
      dodecyltrimethylammonium bromide (DTAB). The coating exhibited a more hydrophilic
      and a smoother surface in comparison to uncoated PES surface, making the produced
      PBM membranes more resistant and less prone to be affected by fouling. The anti
      fouling potential of PBM membranes was assessed by using humic acid (HA) as a
      model foulant, evaluating the water permeability decrease as an indicator of the
      fouling propensity of the membranes. PBM membrane performances in terms of dye
      rejection, when applied for model textile wastewater treatment, were also
      evaluated and compared to PES commercial ones. The PBM membranes were finally
      successfully scaled-up (total membrane area 0.33 m2) and applied in a pilot
      membrane bioreactor (MBR) unit for the treatment of real textile wastewater.

PMID- 29335189
TI  - Biofuel production and phycoremediation by Chlorella sp. ISTLA1 isolated from
      landfill site.
AB  - The present study aims to investigate the biofuel production ability and
      potential of heavy metal remediation of Chlorella sp. ISTLA1 isolated from a
      landfill site. The strain was cultured in Bold's Basal medium at different
      concentration of NaHCO3 and pH. Response surface methodology was employed for the
      optimization of nutrient sources for higher lipid production. Under the optimized
      conditions, the yield of lipid and biomass was 365.42 and 833.14 mg L-1
      respectively. GC-MS analysis of lipid indicated the presence of C8 to C31 organic
      compounds consisting mainly of palmitic acid (C16:0), stearic acid (C18:0) and
      oleic acid (C18:1). Additionally, remediation of heavy metals like Zn, Cu, Mn and
      Fe from waste water was observed by AAS and EDX. The removal efficiency was 82.6%
      for Zn, 56.5% for Cu, 79.8% for Mn and 40% for Fe. The study revealed
      simultaneous biodiesel production and waste water treatment by Chlorella sp.
      ISTLA1.

PMID- 29335188
TI  - Electrophoretic deposition of single-source precursors as a general approach for
      the formation of hybrid nanorod array heterostructures.
AB  - HYPOTHESIS: Subjecting colloids to electric fields often results in
      (electrophoretic) deposition on conductive substrates. Dispersing a single-source
      precursor (SSP) of choice in an appropriate solvent, should allow its deposition
      on different substrates. The SSP-solvent interaction might play a role in the
      deposition (e.g., direction, rate, coverage). After thermal decomposition, the
      SSPs convert to the designed material, thus allowing formation of thin films or
      hybrid nanostructures. EXPERIMENTS: Electrophoretic deposition (EPD) was applied
      on two representative SSPs in different solvents. These SSPs were deposited onto
      substrates covered with vertically-aligned ZnO nanorod (NR) arrays. After thermal
      decomposition, hybrid nanostructures were obtained and their morphology and
      interfaces were characterized by electron microscopy, X-ray diffraction, UV-vis,
      and electrochemistry. FINDINGS: Tuning the organic dispersant-SSP interaction
      allows control over the final film morphology, which can result in coating and
      filling of NRs with metal-sulfides or metal-oxides after thermal decomposition of
      the SSP. These findings introduce a new facile method for a fast and large-scale
      uniform deposition of different (nanostructured) thin film semiconductors on a
      variety of substrates. We discuss the influence of the dispersant medium on the
      deposition of metallo-organic SSPs. As an example, the formed ZnO-CdS interface
      supports charge transfer upon illumination.

PMID- 29335190
TI  - Phytochemistry and pharmacology of the genus Leonurus: The herb to benefit the
      mothers and more.
AB  - Plants belonging to the genus Leonurus, also named motherwort, are traditionally
      used for anti-gynecological disorder in East Asia, and for sedative in Europe.
      Chemical investigation of the genus Leonurus not only enriched the natural
      products library, but also enlarged the pharmacological application of this
      traditional herb. In this review, we systematically summarized the structures of
      259 compounds isolated from the genus Leonurus, featured with 147 labdane
      diterpenoids. The reported bioactivity studies up to 2017 are presented in the
      second part, with the main focus on the isolated compounds and also concerning
      the extracts. In addition to the traditional uterine contraction and sedative
      activity, recently the cardiovascular protection effect of leonurine has drawn
      most attention. Other than that, neuroprotection, anti-inflammation, anti-cancer,
      anti-platelet aggregation and many other activities have been assigned to various
      compounds from the genus Leonurus. Among 70 bioactivity references cited in this
      review, 57% of them were concentrated on two alkaloids (leonurine and
      stachydrine), whereas only 20% are about the 147 diterpenoids. Anti-inflammation
      is the major bioactivity discovered so far for the labdane diterpenoids from the
      genus Leonurus, whose further therapeutic potential still remains for
      exploration.

PMID- 29335191
TI  - Effects of alumina nanoparticles on the microstructure, strength and wear
      resistance of poly(methyl methacrylate)-based nanocomposites prepared by friction
      stir processing.
AB  - In this study, alumina-reinforced poly(methyl methacrylate) nanocomposites
      (PMMA/Al2O3) containing up to 20vol% nanoparticles with an average diameter of
      50nm were prepared by friction stir processing. The effects of nanoparticle
      volume fraction on the microstructural features and mechanical properties of PMMA
      were studied. It is shown that by using a frustum pin tool and employing an
      appropriate processing condition, i.e. a rotational speed of 1600rpm/min and
      transverse velocity of 120mm/min, defect free nanocomposites at microscale with
      fine distribution of the nanoparticles can successfully been prepared. Mechanical
      evaluations including tensile, flexural, hardness and impact tests indicate that
      the strength and toughness of the material gradually increases with the
      nanoparticle concentration and reach to a flexural strength of 129MPa, hardness
      of 101 Shore D, and impact energy 2kJ/m2 for the nanocomposite containing 20vol%
      alumina. These values are about 10% and 20% better than untreated and FSP-treated
      PMMA (without alumina addition). Fractographic studies indicate typical brittle
      features with crack deflection around the nanoparticles. More interestingly, the
      sliding wear rate in a pin-on-disk configuration and the friction coefficient are
      reduced up to 50% by addition of alumina nanoparticles. The worn surfaces exhibit
      typical sliding and ploughing features.

PMID- 29335192
TI  - Isolated and modulated effects of topology and material type on the mechanical
      properties of additively manufactured porous biomaterials.
AB  - In this study, we tried to quantify the isolated and modulated effects of
      topological design and material type on the mechanical properties of AM porous
      biomaterials. Towards this aim, we assembled a large dataset comprising the
      mechanical properties of AM porous biomaterials with different topological
      designs (i.e. different unit cell types and relative densities) and material
      types. Porous structures were additively manufactured from Co-Cr using a
      selective laser melting (SLM) machine and tested under quasi-static compression.
      The normalized mechanical properties obtained from those structures were compared
      with mechanical properties available from our previous studies for porous
      structures made from Ti-6Al-4V and pure titanium as well as with analytical
      solutions. The normalized values of elastic modulus and yield stress were found
      to be relatively close to each other as well as in agreement with analytical
      solutions regardless of material type. However, the material type was found to
      systematically affect the mechanical properties of AM porous biomaterials in
      general and the post-elastic/post-yield range (plateau stress and energy
      absorption capacity) in particular. To put this in perspective, topological
      design could cause up to 10-fold difference in the mechanical properties of AM
      porous biomaterials while up to 2-fold difference was observed as a consequence
      of changing the material type.

PMID- 29335193
TI  - Damage mechanisms in bioactive glass matrix composites under uniaxial
      compression.
AB  - The damage and crack resistance improvement of bioactive glass is of prime
      importance, particularly when applied to the repair of load-bearing bones. The
      present contribution is focused on the prediction of damage mechanisms and crack
      resistance under uniaxial compression of bioactive glass matrix composites
      reinforced with a particulate phase. In order to characterize the effects of
      voids and particles on the damage mechanisms and the macro-response, a two-step
      homogenization is performed by considering the two phases existing at two
      different scales: micro/meso through the homogenization of the porous matrix and
      then meso/macro through the periodic micro-field approach. The damage in the
      bioactive glass matrix is computed via an anisotropic stress-based damage model,
      implemented into a finite element program. Failure resulting of excessive damage
      accumulation in the bioactive glass matrix is predicted by a critical damage
      criterion combined with a vanishing element technique. The implication of
      particles in the toughening mechanism as well as the damage and crack resistance
      improvement in this class of porous biomaterials is highlighted via a parametric
      study using the proposed numerical model.

PMID- 29335194
TI  - Characterization and mechanical behaviour of reinforced hydroxyapatite coatings
      deposited by vacuum plasma spray on SS-316L alloy.
AB  - Hydroxyapatite powder reinforced individually with 10wt percentage (wt%) of Al2O3
      and ZrO2 (HA + 10wt% Al2O3 and HA + 10wt% ZrO2) was thermally sprayed onto SS
      316L substrate with a bond coat of Zirconia by vacuum plasma spray (VPS)
      technique. The resulted coatings were heat treated at 700 degrees C for 1h to
      study its effects on microstructural and mechanical properties of the deposited
      coatings. The characterization of the coatings was carried out using scanning
      electron microscope, x-ray diffraction, porosity, surface roughness and
      crystallinity using Rietveld analysis. The results indicated that after post
      coating heat treatment substantial decrease in porosity was witnessed along with
      significant improvement in crystallinity. Besides, the hardness across the cross
      section of the coatings and bond strength was considerably improved; however the
      hardness of top coat was reduced owing to the loosening of un-melted and
      partially melted particles by diffusion process which takes place during heat
      treatment.

PMID- 29335195
TI  - Periprocedural Anticoagulation for Catheter Ablation of Atrial Fibrillation:
      Practical Implications for Perioperative Management.

PMID- 29335196
TI  - Percutaneous Transcatheter Valve-in-Valve Implantation for Prosthetic Valve
      Disease-An Analysis of Evolving Data and Technology.

PMID- 29335197
TI  - Antifungal efficacy of Au@ carbon dots nanoconjugates against opportunistic
      fungal pathogen, Candida albicans.
AB  - In the current study, we have investigated the toxicological effect of a novel
      hydrophilic nanoconjugate gold@carbon dot (Au@CD) and carbon dots (CDs) on the
      opportunistic fungal pathogen, Candida albicans. A homogenous experimental
      analysis was conducted for determining the toxicity of Au@CDs nanoconjugates of
      five different sizes ranging from 22 +/- 2 to 35 +/- 3 nm prepared using the
      carbon dots of mean hydrodynamic radius 12 +/- 1 nm. The smallest size of
      nanoconjugate was synthesized using 0.3 mg ml-1 HAuCl4 precursor. Our study for
      the first time, conclusively establishes the size-dependent toxicity effect of
      these characterized nanoconjugates against the abovementioned fungal pathogen.
      The MIC80 value of smaller sized Au@CDs nanoconjugates, S1-S3 samples were 250,
      500 and 500 MUg ml-1, respectively, while nanoconjugates of Rh diameter greater
      than 30 nm (S4 and S5 samples) did not show any toxicity. The results thus
      demonstrate that alteration in composition (carbon vs Au@CDs) exhibits a profound
      effect on the susceptibility of Candida albicans cells. While a size-dependent
      toxicity was observed for the nanoconjugates, CDs were found to be quite toxic
      owing to their small size which facilitated their entry into the cells and
      challenged the biocompatibility of carbon allotropes.

PMID- 29335198
TI  - Triple cell-responsive nanogels for delivery of drug into cancer cells.
AB  - In this report, biocompatible nanogels with multi cell-responsiveness (thermo-,
      pH- and reduction) were fabricated by in situ cross-linking of alginate (AG)
      using cystamine (Cys) as a cross-linker through an emulsion approach, in the
      presence of a thermosensitive polymer, poly(N-isopropylacrylamide) (PNIPAM). The
      AG/PNIPAM nanogels exhibited an abrupt swelling upon temperature increase from 37
      to 25  degrees C under physiological conditions (497 +/- 258 nm at 29  degrees C
      and 147 +/- 48 nm at 37  degrees C). The nanogels were easily taken up by cancer
      cells at high temperature, where temperature variation could induce toxicity
      against cancer cells. Furthermore, the accelerated release under reducible and
      acidic microenvironments inside cells, together their thermosensitivity, made the
      nanogels selectively deliver drug intracellulary to exert a synergistical
      anticancer efficacy, potentiating therir high promise for drug delivery
      application.

PMID- 29335199
TI  - 3-D mineralized silk fibroin/polycaprolactone composite scaffold modified with
      polyglutamate conjugated with BMP-2 peptide for bone tissue engineering.
AB  - In the field of bone tissue engineering, an ideal three-dimensional (3-D)
      scaffold should not only structurally mimic the extracellular matrix (ECM) in
      large tissues but also mechanically support the bone healing process and provide
      biochemical cues to induce osteogenesis. In this study, we investigated the
      feasibility of functionalisation of scaffolds by coupling polyglutamate acid
      conjugated with BMP-2 peptide onto silk fibroin (SF)/polycaprolactone (PCL)
      (SF/PCL) blend nanofibers. The morphology, composition, and mineralisation, were
      confirmed by FE-SEM, XRD, and FT-IR spectroscopy. The FE-SEM images revealed that
      wet-electrospun nanofibrous scaffolds exhibited inter-connected nano/micro-pores
      at different levels, and a different morphology was observed on the 3-D SF/PCL
      scaffold after mineralisation. Furthermore, the binding property and release
      behaviour of the peptide were investigated on this mineralized structure, and
      adipose-derived stem cells were seeded on the composite scaffolds to assay their
      cytocompatibility and osteogenic differentiation capacities. Results suggest that
      the polyglutamate motif (repetitive glutamate amino acids) exhibited markedly
      improved binding properties to mineralized nanofibers, and the mineralized 3-D
      scaffolds with the conjugated with peptide enhances the mRNA expression of
      osteogenic genes. The sponge-like 3-D nanofibrous scaffold mechanically and
      biochemically mimics the regenerative process for applications in bone tissue
      engineering, including the regeneration of calvarial defects.

PMID- 29335200
TI  - Discovery and optimization of phthalazinone derivatives as a new class of potent
      dengue virus inhibitors.
AB  - Using a dengue replicon cell line-based screening, we identified 3
      (dimethylamino)propyl(3-((4-(4-fluorophenyl)-1-oxophthalazin-2(1H)
      yl)methyl)phenyl)carbamate (10a) as a potent DENV-2 inhibitor, with an IC50 value
      of 0.64 MUM. A series of novel phthalazinone derivatives based on hit 10a were
      synthesized and evaluated for their in vitro anti-DENV activity and cytotoxicity.
      The subsequent SAR study and optimization led to the discovery of the most
      promising compound 14l, which displayed potent anti-DENV-2 activity, with low
      IC50 value against DENV-2 RNA replication of 0.13 MUM and high selectivity (SI =
      89.2) with acceptable pharmacokinetics profiles.

PMID- 29335201
TI  - Antitumor activity of pyrrolizines and their Cu(II) complexes: Design, synthesis
      and cytotoxic screening with potential apoptosis-inducing activity.
AB  - Two novel series including Schiff bases of the pyrrolizine-5-carboxamides and
      their Cu(II) complexes were designed, synthesized and analysed using spectral and
      analytical techniques. The analytical results indicated the formation of the
      complexes in 1:1 or 1:2 (Metal:Ligand) ratio. The geometry around the Cu centers
      was confirmed to be tetrahedral or octahedral. The cytotoxic activity of the new
      compounds was evaluated using MCF-7 (human breast adenocarcinoma), A2780 (human
      ovary adenocarcinoma) and HT29 (human colon adenocarcinoma), in addition to MRC5
      (normal human fetal lung fibroblast) cells using the MTT cytotoxicity assay. The
      Schiff base 12c and the Cu complex 13b were the most active in the two series
      with IC50 values in the range of 0.14-2.54 MUM against the three cell lines.
      Also, the Cu complex 13e showed excellent activity against HT29 with IC50 =
      0.05MUM. 7-Cyano-N-(4-methoxyphenyl)-6-((3-phenylallylidene) amino)-2,3-dihydro
      1H-pyrrolizine-5-carboxamide (12c) showed high selectivity (6-13 folds) for
      cancerous cells over normal cells; and it induced marginal increases in the G1
      and S phases of MCF-7 cells during cell cycle analysis, while compound 13b
      increased the MCF-7 Sub-G1 proapoptotic population, and blocked cells in the G2-M
      phase in a dose dependent manner. The annexin V apoptosis assay revealed the
      ability of compounds 12c and 13b to increase the early apoptotic MCF-7 cell
      populations two and three fold, respectively. Furthermore, these findings were
      supported by data showing that the two compounds (12c and 13b) elicit cytotoxic
      activity. Taken together, the data presented in this study warrants further in
      vitro and in vivo investigations.

PMID- 29335202
TI  - 5-Bromo-oxoisoaporphine platinum(II) complexes exhibit tumor cell cytotoxcicity
      via inhibition of telomerase activity and disruption of c-myc G-quadruplex DNA
      and mitochondrial functions.
AB  - Two platinum(II) complexes [Pt(L)(DMSO)Cl] (1) and [Pt(L)(pn)]Cl (2) with 5-bromo
      oxoisoaporphine (H-L) were synthesized. We found that the two new platinum(II)
      complexes were more selective for Hep-G2 tumor cells than for normal cells (HL
      7702, WI-38 and L-o2 cell lines). 5-Bromine-oxoisoaporphine platinum(II) complex
      2 was a telomerase inhibitor targeting c-myc G4, and it triggered Hep-G2 cell
      apoptosis more potently than complex 1. Moreover, they induced cell apoptosis via
      disruption of mitochondrial functions. Significantly increased ROS level, loss of
      Deltapsi, decrease of bcl-2 level, and increase of some of the mitochondria
      initiated apoptosis protein levels (including bax, Cyt C, caspase-3, caspase-9,
      and apaf-1) were observed in Hep-G2 cells. In brief, complexes 1 and 2 triggered
      Hep-G2 cell apoptosis mainly through inhibiting telomerase activity by
      interacting with c-myc promoter elements and disruption of mitochondrial pathway.
      Our results also showed the effects of second ligands on the in vitro antitumor
      activity in the order of pn > Cl and DMSO.

PMID- 29335203
TI  - Inhibitor of the human telomerase reverse trancriptase (hTERT) gene promoter
      induces cell apoptosis via a mitochondrial-dependent pathway.
AB  - Telomerase is aberrantly expressed in many cancers and plays an important role in
      the development of cellular immortality and oncogenesis, which makes it a
      potential cancer therapeutic target for drug discovery. Here, we constructed a
      firefly luciferase reporter driven by the human telomerase reverse trancriptase
      (hTERT) gene promoter to screen for inhibitory compounds. Compound 5c was
      discovered and shown to significantly inhibit the promoter activity of hTERT
      gene. Furthermore, five analogs of compound 5c were synthesized, and compound 8b
      was shown to be a more potent inhibitor of hTERT gene promoter activity and
      subsequent expression of hTERT mRNA and protein. The viability of HeLa cells was
      inhibited by a knockdown of hTERT gene expression, and the same effect was also
      observed by treating with compound 8b. Moreover, our results indicated that
      compound 8b induced apoptosis of HeLa cells, and activated caspase-9 and caspase
      3 enzymes. Taken together, these results suggested that compound 8b down
      regulates the expression of hTERT and induces mitochondrial-dependent apoptosis.

PMID- 29335205
TI  - Design and synthesis of 2-(4,5,6,7-tetrahydrothienopyridin-2-yl)-benzoimidazole
      carboxamides as novel orally efficacious Poly(ADP-ribose)polymerase (PARP)
      inhibitors.
AB  - The nuclear protein poly(ADP-ribose) polymerases-1/2 (PARP-1/2) are involved in
      DNA repair damaged by endogenous or exogenous process. And PARP-1/2 inhibitors
      have been proved to be clinically efficacious for DNA repair deficient tumors in
      the past decade. We have developed a series of 4,5,6,7-tetrahydrothienopyridin-2
      yl benzimidazole carboxamides as novel and potent PARP-1/2 inhibitors. The best
      compound resulted from this series is compound 27 which displays excellent PARP-1
      and PARP-2 inhibitory activity with IC50 of 18 nM and 42 nM, respectively.
      Furthermore, it can selectively kill BRCA2 deficient V-C8 cells with a CC50 of
      920 nM. In the MDA-MB-436 (BRCA-1 mutant) xenograft model, this compound was well
      tolerated and showed single-agent activity. Based on the results above, compound
      27 has been selected as a lead candidate targeting PARP-1/2 and its preclinical
      characterization is also underway.

PMID- 29335204
TI  - Synthesis and biological evaluation of bifendate derivatives bearing 6,7-dihydro
      dibenzo[c,e]azepine scaffold as potential P-glycoprotein and tumor metastasis
      inhibitors.
AB  - As a continuation of previous research, fifteen bifendate derivatives bearing 6,7
      dihydro-dibenzo [c,e]azepine scaffold were synthesized and evaluated as P-gp
      medicated multidrug resistance (MDR) reversal agents. Biological evaluation
      indicated that compounds 6k and 9c more potently reversed P-gp-mediated MDR than
      bifendate and verapamil (VRP) by blocking P-gp mediated drug efflux function and
      not by decreasing P-gp expression in K562/A02 MDR cells. Interestingly, wound
      healing and chamber migration assay showed that 6k and 9c could significantly
      attenuate the migration of MDA-MB-231 cells. Notably, 6k and 9c could markedly
      suppress the invasive activity of MDA-MB-231 cells, thus displayed potential anti
      metastasis activity. Preliminary mechanism studies indicated that the anti
      metastasis activity of 6k and 9c was associated with their inhibitory effect on
      the activity and expression of MMP-2 and MMP-9. These results, together with the
      MDR reversal results indicated that compounds 6k and 9c might be promising leads
      for developing novel anti-cancer agents with P-gp and tumor metastasis inhibitory
      activities.

PMID- 29335206
TI  - Synthesis and biological evaluation of 4-amino-5-cinnamoylthiazoles as chalcone
      like anticancer agents.
AB  - A series of 4-amino-5-cinnamoylthiazoles 3a-p were designed and synthesized as
      chalcone-like anticancer agents. The synthesized derivatives 3a-p were evaluated
      for their in vitro antiproliferative activities against three different human
      cancer cell lines including MCF-7, HepG2 and SW480. Most of compounds could
      significantly prevent proliferation of tested cell lines. In particular, the
      pyrrolidine derivative 3e namely (E)-1-(4-amino-2-(pyrrolidin-1-yl)thiazol-5-yl)
      3-(2,4-dichlorophenyl)prop-2-en-1-one showed promising activity, especially
      against HepG2 cells (IC50 = 10.6 MUg/ml). Flow cytometric analyses revealed that
      the prototype compound 3e can prevent the proliferation of HepG2 cells by
      blockade of the cell cycle at the G2 phase and induction of apoptosis.

PMID- 29335207
TI  - Synthesis and biological evaluation of 3-(2-aminoethyl) uracil derivatives as
      gonadotropin-releasing hormone (GnRH) receptor antagonists.
AB  - We investigated a series of uracil analogues by introducing various substituents
      on the phenyl ring of the N-3 aminoethyl side chain and evaluated their
      antagonistic activity against human gonadotropin-releasing hormone (GnRH)
      receptors. Analogues with substituents at the ortho or meta position demonstrated
      potent in vitro antagonistic activity. Specifically, the introduction of a 2-OMe
      group enhanced nuclear factor of activated T-cells (NFAT) inhibition up to 6-fold
      compared to the unsubstituted analogue. We identified compound 12c as a highly
      potent GnRH antagonist with moderate CYP inhibition. Compound 12c showed potent
      and prolonged LH suppression after a single dose was orally administered in
      castrated monkeys compared to a known antagonist, Elagolix. We believe that our
      SAR study offers useful insights to design GnRH antagonists as a potential
      treatment option for endometriosis.

PMID- 29335208
TI  - New findings on the d(TGGGAG) sequence: Surprising anti-HIV-1 activity.
AB  - The biological relevance of tetramolecular G-quadruplexes especially as anti-HIV
      agents has been extensively reported in the literature over the last years. In
      the light of our recent results regarding the slow G-quadruplex folding kinetics
      of ODNs based on d(TGGGAG) sequence, here we report a systematic anti-HIV
      screening to investigate the impact of the G-quadruplex folding on their anti-HIV
      activity. In particular, varying the single stranded concentrations of ODNs, it
      has been tested a pool of ODN sample solutions with different G-quadruplex
      concentrations. The anti-HIV assays have been designed favouring the limited
      kinetics involved in the tetramolecular G4-association based on the d(TGGGAG)
      sequence. Aiming to determine the stoichiometry of G-quadruplex structures in the
      same experimental conditions of the anti-HIV assays, a native gel electrophoresis
      was performed. The gel confirmed the G-quadruplex formation for almost all sample
      solutions while showing the formation of high order G4 structures for the more
      concentrated ODNs solutions. The most significant result is the discovery of a
      potent anti-HIV activity of the G-quadruplex formed by the natural d(TGGGAG)
      sequence (IC50 = 14 nM) that, until now, has been reported to be completely
      inactive against HIV infection.

PMID- 29335209
TI  - Chameleon-like behavior of indolylpiperidines in complex with cholinesterases
      targets: Potent butyrylcholinesterase inhibitors.
AB  - Alzheimer's disease (AD) is the most common form of dementia worldwide with an
      increasing prevalence for the next years. The multifactorial nature of AD
      precludes the design of new drugs directed to a single target being probably one
      of the reasons for recent failures. Therefore, dual binding site
      acetylcholinesterase (AChE) inhibitors have been revealed as cognitive enhancers
      and beta-amyloid modulators offering an alternative in AD therapy field. Based on
      the dual ligands NP61 and donepezil, the present study reports the synthesis of a
      series of indolylpiperidines hybrids to optimize the NP61 structure preserving
      the indole nucleus, but replacing the tacrine moiety of NP61 by benzyl piperidine
      core found in donepezil. Surprisingly, this new family of indolylpiperidines
      derivatives showed very potent and selective hBuChE inhibition. Further studies
      of NMR and molecular dynamics have showed the capacity of these hybrid molecules
      to change their bioactive conformation depending on the binding site, being
      capable to inhibit with different shapes BuChE and residually AChE.

PMID- 29335210
TI  - Privileged scaffolds as MAO inhibitors: Retrospect and prospects.
AB  - This review aims to be a comprehensive, authoritative, critical, and readable
      review of general interest to the medicinal chemistry community because it
      focuses on the pharmacological, chemical, structural and computational aspects of
      diverse chemical categories as monoamine oxidase inhibitors (MAOIs). Monoamine
      oxidases (MAOs), namely MAO-A and MAO-B represent an enormously valuable class of
      neuronal enzymes embodying neurobiological origin and functions, serving as
      potential therapeutic target in neuronal pharmacotherapy, and hence we have
      coined the term "Neurozymes" which is being introduced for the first time ever.
      Nowadays, therapeutic attention on MAOIs engrosses two imperative categories; MAO
      A inhibitors, in certain mental disorders such as depression and anxiety, and MAO
      B inhibitors, in neurodegenerative disorders like Alzheimer's disease (AD) and
      Parkinson's disease (PD). The use of MAOIs declined due to some potential side
      effects, food and drug interactions, and introduction of other classes of drugs.
      However, curiosity in MAOIs is reviving and the recent developments of new
      generation of highly selective and reversible MAOIs, have renewed the therapeutic
      prospective of these compounds. The initial section of the review emphasizes on
      the detailed classification, structural and binding characteristics, therapeutic
      potential, current status and future challenges of the privileged pharmacophores.
      However, the chemical prospective of privileged scaffolds such as; aliphatic and
      aromatic amines, amides, hydrazines, azoles, diazoles, tetrazoles, indoles,
      azines, diazines, xanthenes, tricyclics, benzopyrones, and more interestingly
      natural products, along with their conclusive SARs have been discussed in the
      later segment of review. The last segment of the article encompasses some patents
      granted in the field of MAOIs, in a simplistic way.

PMID- 29335211
TI  - Synthesis of carbazole derivatives containing chalcone analogs as non
      intercalative topoisomerase II catalytic inhibitors and apoptosis inducers.
AB  - Novel topoisomerase II (Topo II) inhibitors have gained considerable interest for
      the development of anticancer agents. In this study, a series of carbazole
      derivatives containing chalcone analogs (CDCAs) were synthesized and investigated
      for their Topo II inhibition and cytotoxic activities. The results from Topo II
      mediated DNA relaxation assay showed that CDCAs could significantly inhibit the
      activity of Topo II, and the structure-activity relationship indicated the
      halogen substituent in phenyl ring play an important role in the activity.
      Further mechanism studies revealed that CDCAs function as non-intercalative Topo
      II catalytic inhibitors. Moreover, some CDCAs showed micromolar cytotoxic
      activities. The most potent compound 3h exhibited notable growth inhibition
      against four human cancer cell lines. Flow cytometric analysis revealed that
      compounds 3d and 3h arrested the HL-60 cells in sub G1 phase by induction of
      apoptosis. It was further confirmed by Annexin-V-FITC binding assay. Western blot
      analysis revealed that compound 3h induces apoptosis likely through the
      activation of caspase proteins.

PMID- 29335212
TI  - Synthesis and biological evaluation of novel bavachinin analogs as anticancer
      agents.
AB  - A library of 28 analogs of bavachinin including aliphatic and aromatic ethers,
      epoxide, chalcone, oxime, semicarbazide, oxime ether and triazole derivatives
      have been synthesized and evaluated for cytotoxicity against four different human
      cancer cell lines. Bio-evaluation studies exhibited better cytotoxic profile for
      many analogs compare to bavachinin. Best results were observed for a 1,2,3
      triazole analog (17i) with IC50 values 7.72, 16.08, 7.13 and 11.67 MUM against
      lung (A549), prostate (PC-3), colon (HCT-116) and breast (MCF-7) cancer cell
      lines respectively. This analog showed three and four fold improvement in
      cytotoxicity against HCT-116 and A549 cell lines than parent molecule (1).
      Structure activity relationship (SAR) study for all synthesized analogs was
      carried out. Further, mechanistic study of the lead molecule (17i) revealed that
      it inhibits colony formation and in vitro migration of human colon cancer cells
      (HCT-116). Also, it induced the morphological changes and mediated the apoptotic
      cell death of HCT-116 cells with perturbance in mitochondrial membrane potential
      (MMP) and PARP cleavage.

PMID- 29335213
TI  - Jietacins, azoxy antibiotics with potent nematocidal activity: Design, synthesis,
      and biological evaluation against parasitic nematodes.
AB  - Jietacins, an azoxy antibiotic class of chemicals, were isolated from the culture
      broth of Streptomyces sp. KP-197. They have a unique structural motif, including
      a vinyl azoxy group and a long acyclic aliphatic chain, which is usually branched
      but non-branched in the case of jietacin C. During a drug discovery program, we
      found that jietacins display potent anthelmintic activity against parasitic
      nematodes and that jietacin A has a moderate or low acute toxicity (LD50 > 300
      mg/kg) and no mutagenic potential in a mini Ames screen. This suggests that
      jietacins have potential for drug discovery research. In order to create a novel
      anthelmintic agent, we performed design, synthesis, and biological evaluation of
      jietacin derivatives against parasitic nematodes. Of these derivatives, we found
      that a fully synthesized simplified derivative exhibited better anthelmintic
      activity against three parasitic nematodes than natural jietacins. In addition,
      it had a better efficacy in vivo through oral administration against a mouse
      nematode. This indicated that the azoxy motif could prove useful as a template
      for anthelmintic discovery, possibly creating a class of anthelmintic with novel
      skeletons, a potential new mode of action, and providing further insight for
      rational drug design.

PMID- 29335215
TI  - Removing antimony from waste lead storage batteries alloy by vacuum displacement
      reaction technology.
AB  - With the wide application of lead acid battery, spent lead acid battery has
      become a serious problem to environmental protection and human health. Though
      spent battery can be a contaminant if not handled properly, it is also an
      important resource to obtain refined lead. Nowadays, the Sb-content in lead
      storage batteries is about 0.5-3 wt%, which is higher than the Sb-content in the
      crude lead. However, there are few reports about the process of removing antimony
      from high-antimony lead bullion. In this study, vacuum displacement reaction
      technology, a new process for removing antimony from high-antimony lead melts,
      was investigated. During this process, lead oxide was added to the system and
      antimony from lead melts was converted into antimony trioxide, which easily was
      evaporated under vacuum so that antimony was removed from lead melts. The
      experimental results demonstrated that Sb-content in lead melts decreased from
      2.5% to 23 ppm under following conditions: mass ratio of PbO/lead bullion of
      0.33, residual gas pressure of 30 Pa, melt temperature of 840  degrees C,
      reaction time of 60 min. The distillate gotten can be used as by-product to
      produce antimony white. Moreover, this study is of importance to recycling of
      waste lead storage batteries alloy.

PMID- 29335214
TI  - In vivo potent BM635 analogue with improved drug-like properties.
AB  - BM635 is the hit compound of a promising anti-TB compound class. Herein we report
      systematic variations around the central pyrrole core of BM635 and we describe
      the design, synthesis, biological evaluation, pharmacokinetic analysis, as well
      as in vivo TB mouse efficacy studies of novel BM635 analogues that show improved
      physicochemical properties. This hit-to-lead campaign led to the identification
      of a new analogue, 4-((1-isopropyl-5-(4-isopropylphenyl)-2-methyl-1H-pyrrol-3
      yl)methyl)morpholine (17), that shows excellent activity (MIC = 0.15 MUM; SI =
      133) against drug-sensitive Mycobacterium tuberculosis strains, as well as
      efficacy in a murine model of TB infection.

PMID- 29335216
TI  - A new screened microbial consortium OEM2 for lignocellulosic biomass
      deconstruction and chlorophenols detoxification.
AB  - Recalcitrance limits biomass application in biorefinery. It is even more so when
      toxic chlorophenols are present. In this study, we screened a microbial
      consortium, OEM2, for lignocellulose deconstruction and chlorophenols
      detoxification through a short-term and efficient screening process. Microbial
      consortium OEM2 had a good buffer capability in the cultivation process and
      exhibited a high xylanase activity, with over 85% hemicellulose degradation
      within 12 days. Throughout the treatment process, 41.5% rice straw decomposition
      on day 12 and around 75% chlorophenols (MCP, 2,4-DCP, 2,4,6-TCP) removal on day
      9, were recorded. Moreover, Fourier translation infrared spectroscopy (FTIR)
      analysis indicated that chemical bonds and groups (eg. hydrogen-bond, beta-1,4
      glycosidic bond, lignin-carbohydrate cross-linking) in the rice straw were
      broken. Cuticle and silica layer destruction and subsequent exposed cellulose
      fibers were observed by scanning electron microscopy (SEM). Microbial consortium
      OEM2 diversity analysis by 16S rRNA gene sequencing indicated that Proteobacteria
      (41.3%) was the most abundant phylum and the genera Paenibacillus and Pseudomonas
      played an important role in the lignocellulose decomposition and chlorophenols
      detoxification. This study developed a faster and more efficient strategy to
      screen a specific microbial consortium. And the new microbial consortium, OEM2,
      makes lignocellulose more accessible and complex pollutants unproblematic in the
      further biorefinery process.

PMID- 29335217
TI  - Synthesis and characterisation of calix[4]arene based bis(triazole)
      bis(hexahydroquinoline): Probing highly selective fluorescence quenching towards
      mercury (Hg2+) analyte.
AB  - In the present study, we are reporting the synthesis of a triazoles incorporated
      fluorescent hexahydroquinoline appended calix[4]arene 7 and its highly selective
      optical recognition ability towards Hg2+. The optical sensor 7 was synthesized
      via two different synthetic pathways and unambiguously characterized by mass
      spectrometry and NMR spectroscopy. The stoichiometric ratio between 7 and Hg2+
      was determined as 1:1 based on Job's plot and ESI-MS analysis. The chemosensor 7
      selectively recognized Hg2+ in the presence of competitive cations such as Cu2+,
      Cu1+, Co3+, Ni2+, Ag1+, Fe2+, Fe3+, Cr3+, Pb2+, Cd2+, Zn2+, Sn2+, Ti4+, Sb3+,
      In3+, Ba2+, Ca2+, and K1+. The limit of detection (LOD) was established as 0.5
      MUM on spectrofluorimetric analysis. According to world health organization (WHO)
      in guidelines for drinking-water quality, the mercury level in natural occurring
      ground and surface water is about ~0.5 MUM (MUg/L). The supra molecule 7 with LOD
      (0.5 MUM) could potentially serve effective receptors for Hg2+ cation. The probe
      7 was applied effectively for detection of Hg2+ in real water samples (i.e. tap
      and deionized water), spiked with Hg2+ (10 MUM) solution. Moreover, the compound
      7 showed non-toxicity during cytotoxic assay against human B cells as they retain
      their morphology. The supramolecule 7 in living cells showed selectivity towards
      Hg2+ in cytotoxic assay with T lymphocytes, evident by morphological changes
      observed via AFM analysis.

PMID- 29335218
TI  - Environmental benefits and drawbacks of composite fuels based on industrial
      wastes and different ranks of coal.
AB  - A promising solution to many problems that thermal power industry is facing today
      would be switching from conventional coal dust combustion to coal-water slurries
      containing petrochemicals (CWSP). Here, we perform an experimental study of the
      most hazardous anthropogenic emissions (sulfur and nitrogen oxides) from the
      combustion of high-potential CWSP. We identify the main benefits and potential
      drawbacks of using CWSP in thermal power industry. A set of components and
      additives to CWSP are explored that significantly affect the environmental and
      energy performance of fuels. The anthropogenic emissions from the combustion of
      CWSP made of widespread coal and oil processing wastes are no higher than those
      from coal dust combustion. Using specialized additives to CWSP, we can change the
      concentrations of NOx and SOx several times. The most appealing additives to CWSP
      are sawdust, straw, charcoal, limestone, and glycerol. They provide better
      environmental, economic, and energy performance and improve the rheological
      properties of CWSP. Waste oils and oil sludge added to CWSP may impair the
      environmental performance but boost the cost and energy efficiency. Using coal
      water slurries containing petrochemicals as a fuel at thermal power plants is an
      environmentally friendly as well as cost- and energy-efficient way to recover
      industrial wastes.

PMID- 29335219
TI  - Thermal removal of arsenic from copper concentrates: Three-dimensional isothermal
      predominance diagrams for the Cu-As-S-O system.
AB  - The three-dimensional predominance volume diagrams (PVDs) for the system Cu-As-S
      O were constructed at 900 K using [Formula: see text] as independent coordinates.
      The constant total pressure surface was used to identify the equilibrium phases
      that are stable at 0.25 atm total pressure. The isobaric surface superimposed on
      the predominance diagram provides useful insights into the roasting of complex
      copper sulfosalts such as enargite (Cu3AsS4) and tennantite (Cu12As4S13). There
      are nine interior invariant points each with four associated condensed phases at
      900 K. The expanded diagrams showing the stability volumes of each individual
      phase are presented. According to the PVD for the Cu-As-S-O system, the
      transformation of enargite to copper sulfate follows the Cu3AsS4->CuS->CuSO4 or
      Cu3AsS4->Cu2S->CuS->CuSO4 sequence when the pressure of As4O6g is extremely low.
      At high As4O6g pressures however, enargite can directly transform to copper
      sulfate.

PMID- 29335220
TI  - Adeno-associated virus vector-mediated expression of DJ-1 attenuates learning and
      memory deficits in 2, 2', 4, 4'-tetrabromodiphenyl ether (BDE-47)-treated mice.
AB  - Evidence indicates that oxidative stress is the central pathological feature of
      2, 2', 4, 4'-tetrabromodiphenyl ether (BDE-47)-induced neurotoxicity. Protein
      kinase C delta (PKCdelta), an oxidative stress-sensitive kinase, can be
      proteolytically cleaved to yield a catalytically active fragment (PKCdelta-CF)
      that is involved in various neurodegenerative disorders. Here, we showed that BDE
      47 treatment increased ROS, malondialdehyde, and protein carbonyl levels in the
      mouse hippocampus. In turn, excessive ROS induced caspase-3-dependent PKCdelta
      activation and stimulated NF-kappaB p65 nuclear translocation, resulting in
      inflammation in the mouse hippocampus. These changes caused learning and memory
      deficits in BDE-47-treated mice. Treatment with Z-DEVD-fmk, a caspase-3
      inhibitor, or N-acetyl-L-cysteine, an antioxidant, blocked PKCdelta activation
      and subsequently inhibited inflammation, thereby improving learning and memory
      deficits in BDE-47-treated mice. Our data further showed that activation of ROS
      PKCdelta signaling was associated with DJ-1 downregulation, which exerted
      neuroprotective effects against oxidative stress induced by different neurotoxic
      agents. Adeno-associated viral vector-mediated DJ-1 overexpression in the
      hippocampus effectively inhibited excessive ROS production, suppressed caspase-3
      dependent PKCdelta cleavage, blunted inflammation and ultimately reversed
      learning and memory deficits in BDE-47-treated mice. Taken together, our results
      demonstrate that DJ-1 plays a pivotal role in BDE-47-induced neurotoxic effects
      and learning and memory deficits.

PMID- 29335221
TI  - Highly efficient solar-driven photocatalytic degradation on environmental
      pollutants over a novel C fibers@MoSe2 nanoplates core-shell composite.
AB  - As an important member of two-dimensional transition metal dichalcogenides, MoSe2
      has a wide range of photoelectrochemical properties. However, MoSe2 alone can not
      directly be used as photocatalyst for its poor performance owing to the strong
      recombination of photogenerated electron-hole pairs. Here, we propose a novel C
      fibers@MoSe2 nanoplates core-shell composite, which was prepared by a facile, one
      step thermal evaporation method. The composite has a remarkable feature of
      numerous MoSe2 thin nanoplates grown in-situ, densely and even vertically on the
      surface of the C fibers. Due to the effective separation of photogenerated
      electron-hole pairs promoted by the prompt transfer of photogenerated electrons
      through C fibers, compared with commercially available pure MoSe2 powder, such
      composite exhibits greatly improved solar-driven photocatalytic activity and high
      stability for the degradation of various organic/inorganic environmental
      pollutants including methylene blue, rhodamine B, p-chlorophenol and K2Cr2O7
      aqueous solutions, showing the great potential for environmental remediation by
      degrading toxic industrial chemicals in waste water using sunlight. Moreover,
      this one-step thermal evaporation is an easy-handling, eco-friendly and low-cost
      synthesis method, which is suitable for large-scale production.

PMID- 29335222
TI  - Quasi-polymeric construction of stable perovskite-type LaFeO3/g-C3N4
      heterostructured photocatalyst for improved Z-scheme photocatalytic activity via
      solid p-n heterojunction interfacial effect.
AB  - Materials of perovskite-type structure have attracted considerable attention for
      their applications in photocatalysis. In this study, a novel composite of p-type
      LaFeO3 microsphere coated with n-type nanosized graphitic carbon nitride
      nanosheets was constructed by the quasi-polymeric calcination method with the aid
      of electrostatic self-assembly interaction. Results indicate that the LaFeO3/g
      C3N4p-n heterostructured photocatalyst obtained, in contrast to the pure
      constituents, enabled improved visible-light absorption, and more efficient
      separation and migration of charge carriers via solid p-n heterojunction
      interfacial effect. Correspondingly, the LaFeO3/g-C3N4 composite allowed for
      higher visible-light-responsive photocatalytic activity for the degradation of
      Brilliant Blue, which was 16.9 and 7.8 times that of pristine g-C3N4 and LaFeO3,
      respectively. The photocatalytic degradation of Brilliant Blue was ascribed to
      the combined contributions of the photogenerated holes (h+), superoxide radicals
      (O2-) and hydroxyl radicals (OH). Based on solid p-n heterojunction interfacial
      interaction, a Z-scheme charge carrier transfer pathway integrated with the dye
      sensitization effect is proposed as the underlying mechanism of the
      photocatalytic reaction process. Therefore, we believe that the perovskite-type
      LaFeO3/g-C3N4 Z-scheme photcatalyst promotes the development of photocatalysis
      and holds much promise for environmental remediation.

PMID- 29335223
TI  - Electron CHanneling ORientation Determination (eCHORD): An original approach to
      crystalline orientation mapping.
AB  - We present a proof-of-concept attesting the feasability to obtain orientation
      maps of polycrystalline materials within a conventional Scanning Electron
      Microscope (SEM) using a standard goniometer and Back Scattered Electron (BSE)
      detector. The described method is based on the analysis of the contrast variation
      of grains due to the channeling of incident electrons on a rotating sample. On
      each pixel of the map, experimental intensity profiles as a function of the
      rotation angle are obtained and compared with simulated ones to retrieve the
      orientation. From first results on aluminum polycrystals, the angular resolution
      is estimated to be better than one degree.

PMID- 29335224
TI  - Adaptive-scanning, near-minimum-deformation atomic force microscope imaging of
      soft sample in liquid: Live mammalian cell example.
AB  - In this paper, an adaptive-scanning mode (ASM) of atomic force microscope (AFM)
      with near-minimum sample deformation is proposed for imaging live biological
      samples in liquid. Conventional contact mode (CM) imaging of live cells is rather
      slow (scan rate  <  0.2 Hz), and as the imaging speed increases, significant
      deformation of the soft and highly corrugated cell membrane is induced. Such a
      low speed CM imaging of live biological samples is not only time consuming, but
      also incapable of capturing dynamic biological evolutions occurring in seconds to
      minutes. The proposed ASM approach aims to address these issues through two
      synergetic efforts integrated together. First, an adaptive-scanning technique is
      proposed to optimally adjust the lateral scanning speed to accommodate the sample
      topography variation and the probe-sample interaction force, so that the scanning
      caused sample deformation is maintained below the threshold value while the
      overall imaging time is minimized. Secondly, a data-driven iterative feedforward
      control is integrated to the vertical feedback loop along with a gradient-based
      optimization of the deflection set-point to substantially improve the tracking of
      the sample topography while maintaining the vertical sample deformation around
      the minimal. The ASM technique is experimentally validated through imaging live
      human prostate cancer cells on AFM. The experimental results demonstrate that
      compared to the conventional CM imaging, the imaging speed is increased over
      eight times without loss of tracking the topography details of the live cell
      membrane, and the probe-sample interaction force is substantially reduced.

PMID- 29335225
TI  - A systematic comparison of on-axis and off-axis transmission Kikuchi diffraction.
AB  - The capabilities of the novel on-axis transmission Kikuchi diffraction (TKD)
      technique were explored in a systematic comparison with conventional off-axis
      TKD. The effect of experimental parameters on the appearance of on-axis and off
      axis Kikuchi patterns was measured and discussed. In contrast to off-axis TKD, on
      axis TKD is more sensitive to changes in beam current and beam energy and less
      sensitive to changes in working distance and detector distance. Moreover, on-axis
      TKD has a distinct advantage over off-axis TKD due to enhanced pattern intensity,
      which allows reduction of the beam current or an increase in the acquisition
      rate. The physical and effective spatial resolution were measured with detector
      typical parameters. Even though the spatial resolution of both configurations did
      not differ significantly under test conditions, on-axis TKD enables measurement
      over large areas with the determined resolution, whereas off-axis TKD is more
      sensitive to beam drift. Band detection by the Hough-transform led to indexing
      of, on average, one additional Kikuchi band when measuring with on-axis TKD
      compared to off-axis TKD and operated more stable on on-axis patterns.

PMID- 29335226
TI  - Genomic and metabolic characterization of spoilage-associated Pseudomonas
      species.
AB  - Pseudomonas are common spoilage agents of aerobically stored fresh foods. Their
      ability to cause spoilage is species- and may be strain-specific. To improve our
      understanding of the meat and milk spoilage agents Pseudomonas fragi and
      Pseudomonas lundensis, we sequenced the genomes of 12 P. fragi and seven P.
      lundensis isolates. These genomes provided a dataset for genomic analyses. Key
      volatile organic compounds (VOCs) produced or metabolised by the isolates were
      determined during their growth on a beef paste and where possible, metabolic
      activity was associated with gene repertoire. Genome analyses showed that the
      isolates included in this work may belong to more than two Pseudomonas species
      with possible spoilage potential. Pan-genome analyses demonstrated a high degree
      of diversity among the P. fragi and genetic flexibility and diversity may be
      traits of both species. Growth of the P. lundensis isolates was characterised by
      the production of large amounts of 1-undecene, 5-methyl-2-hexanone and methyl-2
      butenoic acid. P. fragi isolates produced extensive amounts of methyl and ethyl
      acetate and the production of methyl esters predominated over ethyl esters. Some
      of the P. fragi produced extremely low levels of VOCs, highlighting the
      importance of strain-specific studies in food matrices. Furthermore, although
      usually not considered to be denitrifiers, all isolates generated molecular
      nitrogen, indicating that at least some steps of this pathway are intact.

PMID- 29335227
TI  - Potential of yeasts isolated from dry-cured ham to control ochratoxin A
      production in meat models.
AB  - The environmental conditions reached during the ripening of dry-cured meat
      products favour the proliferation of moulds on their surface. Some of these
      moulds are hazardous to consumers because of their ability to produce ochratoxin
      A (OTA). Biocontrol using Debaryomyces hansenii could be a suitable strategy to
      prevent the growth of ochratoxigenic moulds and OTA accumulation in dry-cured
      meat products. The aim of this work was to evaluate the ability of two strains of
      D. hansenii to control the growth and OTA production of Penicillium verrucosum in
      a meat model under water activities (aw) values commonly reached during the dry
      cured meat product ripening. The presence of D. hansenii strains triggered a
      lengthening of the lag phase and a decrease of the growth rate of P. verrucosum
      in meat-based media at 0.97 and 0.92 aw. Both D. hansenii strains significantly
      reduced OTA production (between 85.16 and 92.63%) by P. verrucosum in the meat
      based medium at 0.92 aw. Neither absorption nor detoxification of OTA by D.
      hansenii strains seems to be involved. However, a repression of the expression of
      the non-ribosomal peptide synthetase (otanpsPN) gene linked to the OTA
      biosynthetic pathway was observed in the presence of D. hansenii. To confirm the
      protective role of D. hansenii strains, they were inoculated together with P.
      verrucosum Pv45 in dry-fermented sausage and dry-cured ham slices. Although P.
      verrucosum Pv45 counts were not affected by the presence of D. hansenii in both
      meat matrices, a reduction of OTA amount was observed. Therefore, the effect of
      D. hansenii strains on OTA accumulation should be attributed to a reduction at
      transcriptional level. Consequently, native D. hansenii can be useful as
      biocontrol agent in dry-cured meat products for preventing the hazard associated
      with the presence of OTA.

PMID- 29335228
TI  - Irreversible electroporation for locally advanced pancreatic cancer through a
      minimally invasive surgery supported by laparoscopic ultrasound.
AB  - INTRODUCTION: Pancreatic cancer is one of the most lethal cancers worldwide, with
      5-years survival rate as low as 6%. The majority of pancreatic cancer patients
      present locally advanced or metastatic disease at diagnosis. Typically, patients
      affected by locally advanced pancreatic cancer (LAPC) do not undergo radical
      surgery but are treated with focal ablative therapies. However, a high rate of
      morbidity due to the heat sink effect has limited the application of ablative
      techniques on a routine basis in LAPC patients. Irreversible electroporation
      (IRE) has proved to be a new method of LAPC ablation. PRESENTATION OF THE CASE: A
      69-year-old woman affected by LAPC with good response to systemic chemotherapy
      with FOLFIRINOX and residual 35 mm mass in the neck of the pancreas underwent to
      IRE through a minimally invasive surgical approach under laparoscopic ultrasound
      guide. The post-operative course was uneventful and the patient was discharged
      after 5 days. Six months after surgery she had no evidence of distant or
      recurrent disease. DISCUSSION: IRE has previously shown promising results in the
      treatment of LAPC, with relatively acceptable morbidity rates and improvement of
      survival. We report on the application of IRE through a minimally invasive
      surgical approach supported by laparoscopic ultrasound. CONCLUSION: In
      conclusion, we propose a novel technical approach that combines the benefits of
      IRE on the treatment of patients affected by LAPC with the advantages of
      laparoscopic surgery.

PMID- 29335229
TI  - Ciliated cyst of the gallbladder: A new case and literature review.
AB  - INTRODUCTION: The ciliated cyst is a rare anomaly that develops from the anterior
      primitive intestine. Its localization is essentially supra diaphragmatic. It's
      localization in the gallbladder is very uncommon. CASE REPORT: We report the
      first case in Tunisia of a ciliated cyst of the gallbladder in a 34 years old
      woman who was operated for a gallbladder stone and in whom the discovery of a
      cystic mass attached to the neck of the gallbladder was preoperatively. The
      pathologic study did conclude to a ciliated cyst. DISCUSSION: The ciliated cyst
      of the gallbladder is a benign congenital lesion that develops from the anterior
      primitive intestine. The most frequent clinical symptom is abdominal pain and the
      median age is 45 years old. The most frequent location is the neck. This
      pathology affects women more than men. Abdominal ultrasound is not very specific
      exam and describes the ciliated cyst as a cystic lesion often anechogenic and
      sometimes hyperechogenic. The CT-scan as well as the abdominal MRI are very
      helpful of the diagnosis. The positif diagnosis of ciliated cyst is histological.
      CONCLUSION: The recommended current treatment for this rare pathology is surgery
      and it consists of a celioscopic cholecystectomie. The place of conservatory
      treatment hasn't been established due to the rarity of described case and the
      possibility of degeneration.

PMID- 29335230
TI  - Application of a health risk assessment model for cattle exposed to pesticides in
      contaminated drinking waters: A study case from the Pampas region, Argentina.
AB  - Using the USEPA methodology we estimated the probabilistic chronic risks for
      calves and adult cows due to pesticide exposure through oral intake of
      contaminated surface and ground waters in Tres Arroyos County (Argentina).
      Because published data on pesticide toxicity endpoints for cows are scarce, we
      used threshold levels based on interspecies extrapolation methods. The studied
      waters showed acceptable quality for cattle production since none of the
      pesticides were present at high-enough concentrations to potentially affect cow
      health. Moreover, ground waters had better quality than surface waters, with
      dieldrin and deltamethrin being the pesticides associated with the highest risk
      values in the former and the latter water compartments, respectively. Our study
      presents a novel use of the USEPA risk methodology proving it is useful for water
      quality evaluation in terms of pesticide toxicity for cattle production. This
      approach represents an alternative tool for water quality management in the
      absence of specific cattle pesticide regulatory limits.

PMID- 29335231
TI  - Reinvestigating the role of reactive species in the oxidation of organic co
      contaminants during Cr(VI) reactions with sulfite.
AB  - Experimental work was undertaken in this study to re-investigate the mechanisms
      and active species responsible for oxidation of co-contaminants in the
      Cr(VI)/HSO3- reaction system. Batch experiments showed that the degradation rates
      of 4-chlorophenol (4-CP) correlated well with the rates of Cr(VI) reduction by
      sulfite in the same solutions, and that O2(aq) was necessary for the oxidation of
      4-CP. Multiple lines of evidences indicate that Cr(VI)/HSO3- reaction is a SO4-
      based oxidation process. SO3- was generated in Cr(VI)/HSO3- system based on the
      electron spin resonance spectra, which could be transformed to secondary radicals
      (SO4-, SO5-, and HO). The contribution of SO5- was ruled out through almost
      complete inhibition of methanol (MeOH) on 4-CP degradation. Considering the
      negligible inhibition of tert-butanol (TBA) on 4-CP degradation, SO4- was
      identified to be reactive species in Cr(VI)/HSO3- process. This result was
      further verified by almost no degradation of nitrobenzene and the inhibiting
      effect of Cl- in Cr(VI)/HSO3- process. This mechanism is beneficial to
      application of Cr(VI)/HSO3- system in wastewater treatment.

PMID- 29335232
TI  - Smartphone App Using Mindfulness Meditation for Women With Chronic Pelvic Pain
      (MEMPHIS): Protocol for a Randomized Feasibility Trial.
AB  - BACKGROUND: Female chronic pelvic pain (CPP) is defined as intermittent or
      constant pelvic or lower abdominal pain occurring in a woman for at least 6
      months. Up to a quarter of women are estimated to be affected by CPP worldwide
      and it is responsible for one fifth of specialist gynecological referrals in the
      United Kingdom. Psychological interventions are commonly utilized. As waiting
      times and funding capacity impede access to face-to-face consultations, supported
      self-management (SSM) has emerged as a viable alternative. Mindfulness meditation
      is a potentially valuable SSM tool, and in the era of mobile technology, this can
      be delivered to the individual user via a smartphone app. OBJECTIVE: To assess
      the feasibility of conducting a trial of a mindfulness meditation intervention
      delivered by a mobile phone app for patients with CPP. The main feasibility
      objectives were to assess patient recruitment and app adherence, to obtain
      information to be used in the sample size estimate of a future trial, and to
      receive feedback on usability of the app. METHODS: Mindfulness Meditation for
      Women With Chronic Pelvic Pain (MEMPHIS) is a three-arm feasibility trial, that
      took place in two hospitals in the United Kingdom. Eligible participants were
      randomized in a 1:1:1 ratio to one of three treatment arms: (1) the intervention
      arm, consisting of a guided, spoken mindfulness meditation app; (2) an active
      control arm, consisting of a progressive muscle relaxation app; and (3) usual
      care (no app). Participants were followed-up for 6 months. Key feasibility
      outcomes included the time taken to recruit all patients for the study,
      adherence, and estimates to be used in the sample size calculation for a
      subsequent full-scale trial. Upon completion of the feasibility trial we will
      conduct focus groups to explore app usability and reasons for noncompliance.
      RESULTS: Recruitment for MEMPHIS took place between May 2016 and September 2016.
      The study was closed March 2017 and the report was submitted to the NIHR on
      October 26, 2017. CONCLUSIONS: This feasibility trial will inform the design of a
      large multicentered trial to assess the clinical effectiveness of mindfulness
      meditation delivered via a smartphone app for the treatment of CPP. TRIAL
      REGISTRATION: ClinicalTrials.gov: NCT02721108;
      https://clinicaltrials.gov/ct2/show/NCT02721108 (Archived by WebCite at
      http://www.webcitation.org/6wLMAkuaU); BioMed Central: ISRCTN10925965;
      https://www.isrctn.com/ISRCTN10925965 (Archived by WebCite at
      http://www.webcitation.org/6wLMVLuys).

PMID- 29335233
TI  - Internet-Based Group Intervention for Ovarian Cancer Survivors: Feasibility and
      Preliminary Results.
AB  - BACKGROUND: Development of psychosocial group interventions for ovarian cancer
      survivors has been limited. Drawing from elements of cognitive-behavioral stress
      management (CBSM), mindfulness-based stress reduction (MBSR), and acceptance and
      commitment therapy (ACT), we developed and conducted preliminary testing of an
      Internet-based group intervention tailored specifically to meet the needs of
      ovarian cancer survivors. The Internet-based platform facilitated home delivery
      of the psychosocial intervention to a group of cancer survivors for whom
      attending face-to-face programs could be difficult given their physical
      limitations and the small number of ovarian cancer survivors at any one treatment
      site. OBJECTIVE: The aim of this study was to develop, optimize, and assess the
      usability, acceptability, feasibility, and preliminary intended effects of an
      Internet-based group stress management intervention for ovarian cancer survivors
      delivered via a tablet or laptop. METHODS: In total, 9 ovarian cancer survivors
      provided feedback during usability testing. Subsequently, 19 survivors
      participated in 5 waves of field testing of the 10-week group intervention led by
      2 psychologists. The group met weekly for 2 hours via an Internet-based
      videoconference platform. Structured interviews and weekly evaluations were used
      to elicit feedback on the website and intervention content. Before and after the
      intervention, measures of mood, quality of life (QOL), perceived stress, sleep,
      and social support were administered. Paired t tests were used to examine changes
      in psychosocial measures over time. RESULTS: Usability results indicated that
      participants (n=9) performed basic tablet functions quickly with no errors and
      performed website functions easily with a low frequency of errors. In the field
      trial (n=19), across 5 groups, the 10-week intervention was well attended.
      Perceived stress (P=.03) and ovarian cancer-specific QOL (P=.01) both improved
      significantly during the course of the intervention. Trends toward decreased
      distress (P=.18) and greater physical (P=.05) and functional well-being (P=.06)
      were also observed. Qualitative interviews revealed that the most common
      obstacles participants experienced were technical issues and the time commitment
      for practicing the techniques taught in the program. Participants reported that
      the intervention helped them to overcome a sense of isolation and that they
      appreciated the ability to participate at home. CONCLUSIONS: An Internet-based
      group intervention tailored specifically for ovarian cancer survivors is highly
      usable and acceptable with moderate levels of feasibility. Preliminary
      psychosocial outcomes indicate decreases in perceived stress and improvements in
      ovarian cancer-specific QOL following the intervention. A randomized clinical
      trial is needed to demonstrate the efficacy of this promising intervention for
      ovarian cancer survivors.

PMID- 29335234
TI  - A Patient-Held Smartcard With a Unique Identifier and an mHealth Platform to
      Improve the Availability of Prenatal Test Results in Rural Nigeria: Demonstration
      Study.
AB  - BACKGROUND: Community-based strategies to test for HIV, hepatitis B virus (HBV),
      and sickle cell disease (SCD) have expanded opportunities to increase the
      proportion of pregnant women who are aware of their diagnosis. In order to use
      this information to implement evidence-based interventions, these results have to
      be available to skilled health providers at the point of delivery. Most
      electronic health platforms are dependent on the availability of reliable
      Internet connectivity and, thus, have limited use in many rural and resource
      limited settings. OBJECTIVE: Here we describe our work on the development and
      deployment of an integrated mHealth platform that is able to capture medical
      information, including test results, and encrypt it into a patient-held smartcard
      that can be read at the point of delivery without the need for an Internet
      connection. METHODS: We engaged a team of implementation scientists, public
      health experts, and information technology specialists in a requirement-gathering
      process to inform the design of a prototype for a platform that uses smartcard
      technology, database deployment, and mobile phone app development. Key design
      decisions focused on usability, scalability, and security. RESULTS: We
      successfully designed an integrated mHealth platform and deployed it in 4 health
      facilities across Benue State, Nigeria. We developed the Vitira Health platform
      to store test results of HIV, HBV, and SCD in a database, and securely encrypt
      the results on a Quick Response code embedded on a smartcard. We used a mobile
      app to read the contents on the smartcard without the need for Internet
      connectivity. CONCLUSIONS: Our findings indicate that it is possible to develop a
      patient-held smartcard and an mHealth platform that contains vital health
      information that can be read at the point of delivery using a mobile phone-based
      app without an Internet connection. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT03027258; https://clinicaltrials.gov/ct2/show/NCT03027258 (Archived by WebCite
      at http://www.webcitation.org/6owR2D0kE).

PMID- 29335235
TI  - VA FitHeart, a Mobile App for Cardiac Rehabilitation: Usability Study.
AB  - BACKGROUND: Cardiac rehabilitation (CR) improves outcomes for patients with
      ischemic heart disease or heart failure but is underused. New strategies to
      improve access to and engagement in CR are needed. There is considerable interest
      in technology-facilitated home CR. However, little is known about patient
      acceptance and use of mobile technology for CR. OBJECTIVE: The aim of this study
      was to develop a mobile app for technology-facilitated home CR and seek to
      determine its usability. METHODS: We recruited patients eligible for CR who had
      access to a mobile phone, tablet, or computer with Internet access. The mobile
      app includes physical activity goal setting, logs for tracking physical activity
      and health metrics (eg, weight, blood pressure, and mood), health education,
      reminders, and feedback. Study staff demonstrated the mobile app to participants
      in person and then observed participants completing prespecified tasks with the
      mobile app. Participants completed the System Usability Scale (SUS, 0-100), rated
      likelihood to use the mobile app (0-100), questionnaires on mobile app use, and
      participated in a semistructured interview. The Unified Theory of Acceptance and
      Use of Technology and the Theory of Planned Behavior informed the analysis. On
      the basis of participant feedback, we made iterative revisions to the mobile app
      between users. RESULTS: We conducted usability testing in 13 participants. The
      first version of the mobile app was used by the first 5 participants, and revised
      versions were used by the final 8 participants. From the first version to revised
      versions, task completion success rate improved from 44% (11/25 tasks) to 78%
      (31/40 tasks; P=.05), SUS improved from 54 to 76 (P=.04; scale 0-100, with 100
      being the best usability), and self-reported likelihood of use remained high at
      76 and 87 (P=.30; scale 0-100, with 100 being the highest likelihood). In
      interviews, patients expressed interest in tracking health measures ("I think
      it'll be good to track my exercise and to see what I'm doing"), a desire for
      introductory training ("Initially, training with a technical person, instead of
      me relying on myself"), and an expectation for sharing data with providers ("It
      would also be helpful to share with my doctor, it just being a matter of clicking
      a button and sharing it with my doctor"). CONCLUSIONS: With participant feedback
      and iterative revisions, we significantly improved the usability of a mobile app
      for CR. Patient expectations for using a mobile app for CR include tracking
      health metrics, introductory training, and sharing data with providers. Iterative
      mixed-method evaluation may be useful for improving the usability of health
      technology.

PMID- 29335236
TI  - Tanzania Health Information Technology (T-HIT) System: Pilot Test of a Tablet
      Based System to Improve Prevention of Mother-to-Child Transmission of HIV.
AB  - BACKGROUND: The prevention of mother-to-child transmission (PMTCT) of HIV
      requires innovative solutions. Although routine monitoring is effective in some
      areas, standardized and easy-to-scale solutions to identify and monitor pregnant
      women, test them for HIV, and treat them and their children is still lacking.
      Mobile health (mHealth) offers opportunities for surveillance and reporting in
      rural areas of low- and middle-income countries. OBJECTIVE: The aim of this study
      was to document the preliminary impacts of the Tanzania Health Information
      Technology (T-HIT) system mHealth intervention aimed at health workers for PMTCT
      care delivery and capacity building in a rural area of Tanzania. METHODS: We
      developed T-HIT as a tablet-based system for an electronic data collection system
      designed to capture and report PMTCT data during antenatal, delivery, and
      postnatal visits in Misungwi, Tanzania. T-HIT was tested by health workers in a
      pilot randomized trial comparing seven sites using T-HIT assigned at random to
      seven control sites; all sites maintained standard paper record-keeping during
      the pilot intervention period. We compared numbers of antenatal visits, number of
      HIV tests administered, and women testing positive across all sites. RESULTS:
      Health workers recorded data from antenatal visits for 1530 women; of these, 695
      (45.42%) were tested for HIV and 3.59% (55/1530) tested positive. Health workers
      were unable to conduct an HIV test for 103 women (6.73%, 103/1530) because of
      lack of reagent, which is not captured on paper logs. There was no difference in
      the activity level for testing when comparing sites T-HIT to non-T-HIT sites. We
      observed a significant postintervention increase in the numbers of women testing
      positive for HIV compared with the preintervention period (P=.04), but this was
      likely not attributable to the T-HIT system. CONCLUSIONS: T-HIT had a high degree
      of acceptability and feasibility and is perceived as useful by health workers,
      who documented more antenatal visits during the pilot intervention compared with
      a traditional system of paper logs, suggesting potential for improvements in
      antenatal care for women at risk for HIV.

PMID- 29335237
TI  - "Why Do They Need to Check Me?" Patient Participation Through eHealth and the
      Doctor-Patient Relationship: Qualitative Study.
AB  - BACKGROUND: Roles in the doctor-patient relationship are changing and patient
      participation in health care is increasingly emphasized. Electronic health
      (eHealth) services such as patient accessible electronic health records (PAEHRs)
      have been implemented to support patient participation. Little is known about
      practical use of PAEHR and its effect on roles of doctors and patients.
      OBJECTIVE: This qualitative study aimed to investigate how physicians view the
      idea of patient participation, in particular in relation to the PAEHR system.
      Hereby, the paper aims to contribute to a deeper understanding of physicians'
      constructions of PAEHR, roles in the doctor-patient relationship, and levels and
      limits of involvement. METHODS: A total of 12 semistructured interviews were
      conducted with physicians in different fields. Interviews were transcribed,
      translated, and a theoretically informed thematic analysis was performed.
      RESULTS: Two important aspects were identified that are related to the doctor
      patient relationship: roles and involvement. The physicians viewed their role as
      being the ones to take on the responsibility, determining treatment options, and
      to be someone who should be trusted. In relation to the patient's role, lack of
      skills (technical or regarding medical jargon), motives to read, and patients'
      characteristics were aspects identified in the interviews. Patients were often
      referred to as static entities disregarding their potential to develop skills and
      knowledge over time. Involvement captures aspects that support or hinder patients
      to take an active role in their care. CONCLUSIONS: Literature of at least two
      decades suggests an overall agreement that the paternalistic approach in health
      care is inappropriate, and a collaborative process with patients should be
      adopted. Although the physicians in this study stated that they, in principle,
      were in favor of patient participation, the analysis found little support in
      their descriptions of their daily practice that participation is actualized. As
      seen from the results, paternalistic practices are still present, even if
      professionals might not be aware of this. This can create a conflict between
      patients who strive to become more informed and their questions being interpreted
      as signs of critique and mistrust toward the physician. We thus believe that the
      full potential of PAEHRs is not reached yet and argue that the concept of patient
      empowerment is problematic as it triggers an interpretation of "power" in health
      care as a zero-sum, which is not helpful for the maintenance of the relationship
      between the actors. Patient involvement is often discussed merely in relation to
      decision making; however, this study emphasizes the need to include also
      sensemaking and learning activities. This would provide an alternative
      understanding of patients asking questions, not in terms of "monitoring the
      doctor" but to make sense of the situation.

PMID- 29335240
TI  - "Arrogant" surgeon fined for writing his initials on patients' livers.

PMID- 29335238
TI  - Automating Quality Measures for Heart Failure Using Natural Language Processing:
      A Descriptive Study in the Department of Veterans Affairs.
AB  - BACKGROUND: We developed an accurate, stakeholder-informed, automated, natural
      language processing (NLP) system to measure the quality of heart failure (HF)
      inpatient care, and explored the potential for adoption of this system within an
      integrated health care system. OBJECTIVE: To accurately automate a United States
      Department of Veterans Affairs (VA) quality measure for inpatients with HF.
      METHODS: We automated the HF quality measure Congestive Heart Failure Inpatient
      Measure 19 (CHI19) that identifies whether a given patient has left ventricular
      ejection fraction (LVEF) <40%, and if so, whether an angiotensin-converting
      enzyme inhibitor or angiotensin-receptor blocker was prescribed at discharge if
      there were no contraindications. We used documents from 1083 unique inpatients
      from eight VA medical centers to develop a reference standard (RS) to train
      (n=314) and test (n=769) the Congestive Heart Failure Information Extraction
      Framework (CHIEF). We also conducted semi-structured interviews (n=15) for
      stakeholder feedback on implementation of the CHIEF. RESULTS: The CHIEF
      classified each hospitalization in the test set with a sensitivity (SN) of 98.9%
      and positive predictive value of 98.7%, compared with an RS and SN of 98.5% for
      available External Peer Review Program assessments. Of the 1083 patients
      available for the NLP system, the CHIEF evaluated and classified 100% of cases.
      Stakeholders identified potential implementation facilitators and clinical uses
      of the CHIEF. CONCLUSIONS: The CHIEF provided complete data for all patients in
      the cohort and could potentially improve the efficiency, timeliness, and utility
      of HF quality measurements.

PMID- 29335239
TI  - Comparing Diet and Exercise Monitoring Using Smartphone App and Paper Diary: A
      Two-Phase Intervention Study.
AB  - BACKGROUND: There is increasing recognition that personalized approaches may be
      more effective in helping people establish healthier eating patterns and exercise
      more, and that this approach may be particularly effective in adolescents.
      OBJECTIVE: The objective of this study was to investigate the use of a smartphone
      app (FoodWiz2) in supporting healthy lifestyle choices in adolescence. METHODS:
      Participants (N=34: 11 male, 23 female) aged 16-19 years in full- or part-time
      education were recruited from sixth form colleges, schools, and other further
      education establishments in Norfolk and Suffolk, United Kingdom, between February
      and May 2015. Participants recorded food intake and exercise using a paper diary
      for 4-5 weeks and then used the app for the same duration. Initial nutrition
      education and general support were provided during the paper diary use, but the
      app included personalized messages sent in response to app activity. At the end
      of each study phase, participants completed an online questionnaire to describe
      their experience of using the paper diary and app. RESULTS: Record completion
      declined throughout the study, possibly affected by examination pressure. Food
      intake data showed increased fruit consumption and significantly reduced
      consumption of chocolate snacks (P=.01) and fizzy drinks (P=.002) among
      participants using the app. Questionnaire responses indicated that the app was
      generally preferred to the paper diary, in particular, the app was seen as less
      boring to use (P=.03) and more acceptable in social settings (P<.001).
      CONCLUSIONS: This app-based approach has shown the potential for a more effective
      approach to improving adolescent diet and exercise levels.

PMID- 29335241
TI  - The MFHR1 Fusion Protein Is a Novel Synthetic Multitarget Complement Inhibitor
      with Therapeutic Potential.
AB  - The complement system is essential for host defense, but uncontrolled complement
      system activation leads to severe, mostly renal pathologies, such as atypical
      hemolytic uremic syndrome or C3 glomerulopathy. Here, we investigated a novel
      combinational approach to modulate complement activation by targeting C3 and the
      terminal pathway simultaneously. The synthetic fusion protein MFHR1 links the
      regulatory domains of complement factor H (FH) with the C5 convertase/C5b-9
      inhibitory fragment of the FH-related protein 1. In vitro, MFHR1 showed cofactor
      and decay acceleration activity and inhibited C5 convertase activation and C5b-9
      assembly, which prevented C3b deposition and reduced C3a/C5a and C5b-9
      generation. Furthermore, this fusion protein showed the ability to escape
      deregulation by FH-related proteins and form multimeric complexes with increased
      inhibitory activity. In addition to substantially inhibiting alternative and
      classic pathway activation, MFHR1 blocked hemolysis mediated by serum from a
      patient with aHUS expressing truncated FH. In FH-/- mice, MFHR1 administration
      augmented serum C3 levels, reduced abnormal glomerular C3 deposition, and
      ameliorated C3 glomerulopathy. Taking the unique design of MFHR1 into account, we
      suggest that the combination of proximal and terminal cascade inhibition together
      with the ability to form multimeric complexes explain the strong inhibitory
      capacity of MFHR1, which offers a novel basis for complement therapeutics.

PMID- 29335242
TI  - Effect of Bariatric Surgery on CKD Risk.
AB  - Obesity is linked to the development and progression of CKD, but whether
      bariatric surgery protects against CKD is poorly understood. We, therefore,
      examined whether bariatric surgery influences CKD risk. The study included 2144
      adults who underwent bariatric surgery from March of 2006 to April of 2009 and
      participated in the Longitudinal Assessment of Bariatric Surgery-2 Study cohort.
      The primary outcome was CKD risk categories as assessed by the Kidney Disease
      Improving Global Outcomes (KDIGO) consortium criteria using a combination of eGFR
      and albuminuria. Patients were 79% women and 87% white, with a median age of 46
      years old. Improvements were observed in CKD risk at 1 and 7 years after surgery
      in patients with moderate baseline CKD risk (63% and 53%, respectively), high
      baseline risk (78% and 56%, respectively), and very high baseline risk (59% and
      23%, respectively). The proportion of patients whose CKD risk worsened was <=10%;
      five patients developed ESRD. Sensitivity analyses using year 1 as baseline to
      minimize the effect of weight loss on serum creatinine and differing eGFR
      equations offered qualitatively similar results. Treatment with bariatric surgery
      associated with an improvement in CKD risk categories in a large proportion of
      patients for up to 7 years, especially in those with moderate and high baseline
      risk. These findings support consideration of CKD risk in evaluation for
      bariatric surgery and further study of bariatric surgery as a treatment for high
      risk obese patients with CKD.

PMID- 29335244
TI  - Making the Right Decision: Do Clinical Decision Support Systems for AKI Improve
      Patient Outcomes?

PMID- 29335243
TI  - Nephronectin Regulates Mesangial Cell Adhesion and Behavior in Glomeruli.
AB  - A critical aspect of kidney function occurs at the glomerulus, the capillary
      network that filters the blood. The glomerular basement membrane (GBM) is a key
      component of filtration, yet our understanding of GBM interactions with mesangial
      cells, specialized pericytes that provide structural stability to glomeruli, is
      limited. We investigated the role of nephronectin (Npnt), a GBM component and
      known ligand of alpha8beta1 integrin. Immunolocalization and in situ
      hybridization studies in kidneys of adult mice revealed that nephronectin is
      produced by podocytes and deposited into the GBM. Conditional deletion of Npnt
      from nephron progenitors caused a pronounced increase in mesangial cell number
      and mesangial sclerosis. Nephronectin colocalized with alpha8beta1 integrin to
      novel, specialized adhesion structures that occurred at sites of mesangial cell
      protrusion at the base of the capillary loops. Absence of nephronectin disrupted
      these adhesion structures, leading to mislocalization of alpha8beta1. Podocyte
      specific deletion of Npnt also led to mesangial sclerosis in mice. These results
      demonstrate a novel role for nephronectin and alpha8beta1 integrin in a newly
      described adhesion complex and begin to uncover the molecular interactions
      between the GBM and mesangial cells, which govern mesangial cell behavior and may
      have a role in pathologic states.

PMID- 29335245
TI  - CDK9-mediated phosphorylation controls the interaction of TIP60 with the
      transcriptional machinery.
AB  - The acetyltransferase TIP60 is regulated by phosphorylation, and we have
      previously shown that phosphorylation of TIP60 on S86 by GSK-3 promotes p53
      mediated induction of the BCL-2 protein PUMA. TIP60 phosphorylation by GSK-3
      requires a priming phosphorylation on S90, and here, we identify CDK9 as a
      TIP60S90 kinase. We demonstrate that a phosphorylation-deficient mutant,
      TIP60S90A, exhibits reduced interaction with chromatin, histone 3 and RNA Pol II,
      while its association with the TIP60 complex subunit EPC1 is not affected.
      Consistently, we find a diminished association of TIP60S90A with the MYC gene. We
      show that cells expressing TIP60S90A, but also TIP60S86A, which retains S90
      phosphorylation, exhibit reduced histone 4 acetylation and proliferation. Thus,
      our data indicate that, during transcription, phosphorylation of TIP60 at two
      sites has different regulatory effects on TIP60, whereby S90 phosphorylation
      controls association with the transcription machinery, and S86 phosphorylation is
      regulating TIP60 HAT activity.

PMID- 29335247
TI  - The genetics of domestication: Research into the domestication of livestock and
      companion animals sheds light both on their "evolution" and human history.

PMID- 29335246
TI  - Differential roles of ERRFI1 in EGFR and AKT pathway regulation affect cancer
      proliferation.
AB  - AKT signaling is modulated by a complex network of regulatory proteins and is
      commonly deregulated in cancer. Here, we present a dual mechanism of AKT
      regulation by the ERBB receptor feedback inhibitor 1 (ERRFI1). We show that in
      cells expressing high levels of EGFR, ERRF1 inhibits growth and enhances
      responses to chemotherapy. This is mediated in part through the negative
      regulation of AKT signaling by direct ERRFI1-dependent inhibition of EGFR In
      cells expressing low levels of EGFR, ERRFI1 positively modulates AKT signaling by
      interfering with the interaction of the inactivating phosphatase PHLPP with AKT,
      thereby promoting cell growth and chemotherapy desensitization. These
      observations broaden our understanding of chemotherapy response and have
      important implications for the selection of targeted therapies in a cell context
      dependent manner. EGFR inhibition can only sensitize EGFR-high cells for
      chemotherapy, while AKT inhibition increases chemosensitivity in EGFR-low cells.
      By understanding these mechanisms, we can take advantage of the cellular context
      to individualize antineoplastic therapy. Finally, our data also suggest targeting
      of EFFRI1 in EGFR-low cancer as a promising therapeutic approach.

PMID- 29335248
TI  - Fast neurogenesis from carotid body quiescent neuroblasts accelerates adaptation
      to hypoxia.
AB  - Unlike other neural peripheral organs, the adult carotid body (CB) has a
      remarkable structural plasticity, as it grows during acclimatization to hypoxia.
      The CB contains neural stem cells that can differentiate into oxygen-sensitive
      glomus cells. However, an extended view is that, unlike other catecholaminergic
      cells of the same lineage (sympathetic neurons or chromaffin cells), glomus cells
      can divide and thus contribute to CB hypertrophy. Here, we show that O2-sensitive
      mature glomus cells are post-mitotic. However, we describe an unexpected
      population of pre-differentiated, immature neuroblasts that express
      catecholaminergic markers and contain voltage-dependent ion channels, but are
      unresponsive to hypoxia. Neuroblasts are quiescent in normoxic conditions, but
      rapidly proliferate and differentiate into mature glomus cells during hypoxia.
      This unprecedented "fast neurogenesis" is stimulated by ATP and acetylcholine
      released from mature glomus cells. CB neuroblasts, which may have evolved to
      facilitate acclimatization to hypoxia, could contribute to the CB oversensitivity
      observed in highly prevalent human diseases.

PMID- 29335249
TI  - Hypertension and Diabetes Mellitus: Coprediction and Time Trajectories.
AB  - Type 2 diabetes mellitus and hypertension overlap in the population. In many
      subjects, development of diabetes mellitus is characterized by a relatively rapid
      increase in plasma glucose values. Whether a similar phenomenon occurs during the
      development of hypertension is not known. We analyzed the pattern of blood
      pressure (BP) changes during the development of hypertension in patients with or
      without diabetes mellitus using data from the MCDS (Mexico City Diabetes Study; a
      population-based study of diabetes mellitus in Hispanic whites) and in the FOS
      (Framingham Offspring Study, a community-based study in non-Hispanic whites)
      during a 7-year follow-up. Diabetes mellitus at baseline was a significant
      predictor of incident hypertension (in FOS, odds ratio, 3.14; 95% confidence
      interval, 2.17-4.54) independently of sex, age, body mass index, and familial
      diabetes mellitus. Conversely, hypertension at baseline was an independent
      predictor of incident diabetes mellitus (in FOS, odds ratio, 3.33; 95% CI, 2.50
      4.44). In >60% of the converters, progression from normotension to hypertension
      was characterized by a steep increase in BP values, averaging 20 mm Hg for
      systolic BP within 3.5 years (in MCDS). In comparison with the nonconverters
      group, hypertension and diabetes mellitus converters shared a metabolic syndrome
      phenotype (hyperinsulinemia, higher body mass index, waist girth, BP, heart rate
      and pulse pressure, and dyslipidemia). Overall, results were similar in the 2
      ethnic groups. We conclude that (1) development of hypertension and diabetes
      mellitus track each other over time, (2) transition from normotension to
      hypertension is characterized by a sharp increase in BP values, and (3) insulin
      resistance is one common feature of both prediabetes and prehypertension and an
      antecedent of progression to 2 respective disease states.

PMID- 29335250
TI  - Akap1 Regulates Vascular Function and Endothelial Cells Behavior.
AB  - MitoAKAPs (mitochondrial A kinase anchoring proteins), encoded by the Akap1 gene,
      regulate multiple cellular processes governing mitochondrial homeostasis and cell
      viability. Although mitochondrial alterations have been associated to endothelial
      dysfunction, the role of mitoAKAPs in the vasculature is currently unknown. To
      test this, postischemic neovascularization, vascular function, and arterial blood
      pressure were analyzed in Akap1 knockout mice (Akap1-/- ) and their wild-type
      (wt) littermates. Primary cultures of aortic endothelial cells (ECs) were also
      obtained from Akap1-/- and wt mice, and ECs migration, proliferation, survival,
      and capillary-like network formation were analyzed under different experimental
      conditions. After femoral artery ligation, Akap1-/- mice displayed impaired blood
      flow and functional recovery, reduced skeletal muscle capillary density, and Akt
      phosphorylation compared with wt mice. In Akap1-/- ECs, a significant enhancement
      of hypoxia-induced mitophagy, mitochondrial dysfunction, reactive oxygen species
      production, and apoptosis were observed. Consistently, capillary-like network
      formation, migration, proliferation, and AKT phosphorylation were reduced in
      Akap1-/- ECs. Alterations in Akap1-/- ECs behavior were also confirmed in Akap1-/
      mice, which exhibited a selective reduction in acetylcholine-induced
      vasorelaxation in mesenteric arteries and a mild but significant increase in
      arterial blood pressure levels compared with wt. Finally, overexpression of a
      constitutively active Akt mutant restored vascular reactivity and ECs function in
      Akap1-/- conditions. These results demonstrate the important role of mitoAKAPs in
      the modulation of multiple ECs functions in vivo and in vitro, suggesting that
      mitochondria-dependent regulation of ECs might represent a novel therapeutic
      approach in cardiovascular diseases characterized by endothelial dysfunction.

PMID- 29335251
TI  - Goblet cell carcinomas of the appendix: rare but aggressive neoplasms with
      challenging management.
AB  - Goblet cell carcinomas (GCC) are a rare, aggressive sub-type of appendiceal
      tumours with neuroendocrine features, and controversy exists with regards to
      therapeutic strategy. We undertook a retrospective review of GCC patients
      surgically treated at two tertiary referral centres. Clinical and
      histopathological data were extracted from a prospectively maintained database.
      Survival analyses utilised Kaplan-Meier methodology. Twenty-one patients were
      identified (9 females). Median age at diagnosis was 55 years (range 32-77). There
      were 3, 6 and 9 grade 1, 2 and 3 tumours, respectively. One, 10, 5 and 5 patients
      had stage I, II, III and IV disease at diagnosis, respectively. There were 8, 10
      and 3 Tang class A, B and C tumours, respectively. Index operation was
      appendectomy (n = 12), right hemicolectomy (n = 6) or resections including
      appendix/right colon, omentum and the gynaecological system (n = 3). Eight
      patients underwent completion right hemicolectomy. Surgery for recurrence
      included small bowel resection (n = 2), debulking with peritonectomy and heated
      intraperitoneal chemotherapy, and hysterectomy and bilateral salpingo
      oophorectomy (all n = 1). Median follow-up was 30 months (range 2.5-123). One-, 3
      and 5-year OS was 79.4, 60 and 60%, respectively. Mean OS (1-, 3-, and 5-year
      OS) for Tang class A, B and C tumours were 73.1 months (85.7, 85.7, 51.4%), 83.7
      months (all 66.7%) and 28.5 months (66.7, 66.7%, not reached), respectively.
      Chromogranin A/B and 68Ga-DOTATATE PET/CT were not useful in follow-up, but CEA,
      CA 19-9, CA 125 and 18F-FDG PET/CT identified tumour recurrence. GCC must be
      clearly discriminated from relatively indolent appendiceal neuroendocrine
      neoplasms. 18F-FDG PET/CT and CEA/CA19-9/CA 125 are useful in detecting
      recurrence of GCC.

PMID- 29335253
TI  - Women's reproductive factors and incident cardiovascular disease in the UK
      Biobank.
AB  - BACKGROUND: Studies have suggested that women's reproductive factors are
      associated with the risk of cardiovascular disease (CVD); however, findings are
      mixed. We assessed the relationship between reproductive factors and incident CVD
      in the UK Biobank. METHODS: Between 2006 and 2010, the UK Biobank recruited over
      500 000 participants aged 40-69 years across the UK. During 7 years of follow-up,
      9054 incident cases of CVD (34% women), 5782 cases of coronary heart disease
      (CHD) (28% women), and 3489 cases of stroke (43% women) were recorded among 267
      440 women and 215 088 men without a history of CVD at baseline. Cox regression
      models yielded adjusted hazard ratios (HRs) for CVD, CHD and stroke associated
      with reproductive factors. RESULTS: Adjusted HRs (95% CI) for CVD were 1.10 (1.01
      to 1.30) for early menarche (<12 years), 0.97 (0.96 to 0.98) for each year
      increase in age at first birth, 1.04 (1.00 to 1.09) for each miscarriage, 1.14
      (1.02 to 1.28) for each stillbirth, and 1.33 (1.19 to 1.49) for early menopause
      (<47 years). Hysterectomy without oophorectomy or with previous oophorectomy had
      adjusted HRs of 1.16 (1.06 to 1.28) and 2.30 (1.20 to 4.43) for CVD. Each
      additional child was associated with a HR for CVD of 1.03 (1.00 to 1.06) in women
      and 1.03 (1.02 to 1.05) in men. CONCLUSIONS: Early menarche, early menopause,
      earlier age at first birth, and a history of miscarriage, stillbirth or
      hysterectomy were each independently associated with a higher risk of CVD in
      later life. The relationship between the number of children and incident CVD was
      similar for men and women.

PMID- 29335252
TI  - Diagnostic re-evaluation of congenital hypothyroidism in Macedonia: predictors
      for transient or permanent hypothyroidism.
AB  - BACKGROUND: Diagnostic re-evaluation is important for all patients with
      congenital hypothyroidism (CH) for determining the etiology and identifying
      transient CH cases. Our study is a first thyroxine therapy withdrawal study
      conducted in Macedonian CH patients for a diagnostic re-evaluation. We aimed to
      evaluate the etiology of CH, the prevalence of transient CH and identify
      predictive factors for distinguishing between permanent (PCH) and transient CH
      (TCH). MATERIALS AND METHODS: Patients with CH aged >3 years underwent a trial of
      treatment withdrawal for 4 weeks period. Thyroid function testing (TFT),
      ultrasound and Technetium-99m pertechnetate thyroid scan were performed
      thereafter. TCH was defined when TFT remained within normal limits for at least 6
      month follow-up. PCH was diagnosed when TFT was abnormal and classified according
      the imaging findings. RESULTS: 42 (55%) patients had PCH and 34 (45.0%) patients
      had TCH. Thyroid agenesia was the most prevalent form in the PCH group. Patients
      with TCH had lower initial thyroid-stimulating hormone (TSH) values (P < 0.0001);
      higher serum thyroxine levels (P = 0.0023) and lower mean doses of levothyroxine
      during treatment period (P < 0.0001) than patients with PCH. Initial TSH level
      <30.5 IU/mL and levothyroxine dose at 3 years of age <2.6 mg/kg/day were a
      significant predictive factors for TCH; sensitivity 92% and 100%, specificity
      75.6% and 76%, respectively. CONCLUSION: TCH presents a significant portion of
      patients with CH. Initial TSH value and levothyroxine dose during treatment
      period has a predictive role in differentiating TCH from PCH. Earlier re
      evaluation, between 2 and 3 years age might be considered in some patients
      requiring low doses of levothyroxine.

PMID- 29335254
TI  - Depressed left and right ventricular cardiac output in fetuses of diabetic
      mothers.
AB  - INTRODUCTION: We compared right and left ventricular cardiac output (RVCO and
      LVCO) in fetuses of diabetic mothers (FDM) to a large normal cohort. METHODS: We
      prospectively enrolled 264 normal fetuses and 30 FDM. Fetal CO parameters:
      semilunar valve velocity time integrals (AVVTI, PVVTI), ventricular outflow
      diameters (LVOTD, RVOTD), stroke volumes (AVSV, PVSV) were measured, and LVCO and
      RVCO calculated.  These were normalized using nonlinear regression to estimated
      fetal weight (EFW) to provide means and standard deviations. Among FDMs, mean Z
      scores and 95% confidence limits (CL) were calculated, and compared to zero.
      RESULTS: LVCO, RVCO, and parameters they were calculated from, increased
      predictably and non-linearly with increasing EFW.  In FDM, LVCO was depressed
      (mean Z -1.679, 95% CL -2.404, -0.955, p<0.001), and AVVTI, LVOTD, AVSV
      significantly lower than normal.  Similarly, RVCO (mean Z = -1.119, CL -1.839, 
      0.400, p=0.003), RVOTD (mean -2.085, CL -3.077, -1.093, p<0.001), and PVSV (mean 
      1.184, CL -1.921, -0.446, p=0.003) were lower than normal, however, PVVTI was not
      different (mean Z 0.078, CL -0.552, +0.707, p=0.803). CONCLUSION: Normal
      biventricular stroke volumes and outputs follow a nonlinear regression with EFW.
      FDM have significantly lower right and left heart stroke volumes and outputs for
      weight than do normal fetuses.

PMID- 29335255
TI  - Neighbourhood looking glass: 360o automated characterisation of the built
      environment for neighbourhood effects research.
AB  - BACKGROUND: Neighbourhood quality has been connected with an array of health
      issues, but neighbourhood research has been limited by the lack of methods to
      characterise large geographical areas. This study uses innovative computer vision
      methods and a new big data source of street view images to automatically
      characterise neighbourhood built environments. METHODS: A total of 430 000 images
      were obtained using Google's Street View Image API for Salt Lake City, Chicago
      and Charleston. Convolutional neural networks were used to create indicators of
      street greenness, crosswalks and building type. We implemented log Poisson
      regression models to estimate associations between built environment features and
      individual prevalence of obesity and diabetes in Salt Lake City, controlling for
      individual-level and zip code-level predisposing characteristics. RESULTS:
      Computer vision models had an accuracy of 86%-93% compared with manual
      annotations. Charleston had the highest percentage of green streets (79%), while
      Chicago had the highest percentage of crosswalks (23%) and commercial
      buildings/apartments (59%). Built environment characteristics were categorised
      into tertiles, with the highest tertile serving as the referent group.
      Individuals living in zip codes with the most green streets, crosswalks and
      commercial buildings/apartments had relative obesity prevalences that were 25%
      28% lower and relative diabetes prevalences that were 12%-18% lower than
      individuals living in zip codes with the least abundance of these neighbourhood
      features. CONCLUSION: Neighbourhood conditions may influence chronic disease
      outcomes. Google Street View images represent an underused data resource for the
      construction of built environment features.

PMID- 29335257
TI  - Staphylococcal Superantigens Use LAMA2 as a Coreceptor To Activate T Cells.
AB  - Canonical Ag-dependent TCR signaling relies on activation of the src-family
      tyrosine kinase LCK. However, staphylococcal superantigens can trigger TCR
      signaling by activating an alternative pathway that is independent of LCK and
      utilizes a Galpha11-containing G protein-coupled receptor (GPCR) leading to
      PLCbeta activation. The molecules linking the superantigen to GPCR signaling are
      unknown. Using the ligand-receptor capture technology LRC-TriCEPS, we identified
      LAMA2, the alpha2 subunit of the extracellular matrix protein laminin, as the
      coreceptor for staphylococcal superantigens. Complementary binding assays (ELISA,
      pull-downs, and surface plasmon resonance) provided direct evidence of the
      interaction between staphylococcal enterotoxin E and LAMA2. Through its G4
      domain, LAMA2 mediated the LCK-independent T cell activation by these toxins.
      Such a coreceptor role of LAMA2 involved a GPCR of the calcium-sensing receptor
      type because the selective antagonist NPS 2143 inhibited superantigen-induced T
      cell activation in vitro and delayed the effects of toxic shock syndrome in vivo.
      Collectively, our data identify LAMA2 as a target of antagonists of
      staphylococcal superantigens to treat toxic shock syndrome.

PMID- 29335256
TI  - Recombinant Human Vimentin Binds to P-Selectin and Blocks Neutrophil Capture and
      Rolling on Platelets and Endothelium.
AB  - Leukocyte adhesion to vascular endothelium and platelets is an early step in the
      acute inflammatory response. The initial process is mediated through P-selectin
      glycoprotein ligand-1 (PSGL-1) on leukocytes binding to platelets adhered to
      endothelium and the endothelium itself via P-selectin. Although these
      interactions are generally beneficial, pathologic inflammation may occur in
      undesirable circumstances, such as in acute lung injury (ALI) and ischemia and
      reperfusion injury. Therefore, the development of novel therapies to attenuate
      inflammation may be beneficial. In this article, we describe the potential
      benefit of using a recombinant human vimentin (rhVim) on reducing human leukocyte
      adhesion to vascular endothelium and platelets under shear stress. The addition
      of rhVim to whole blood and isolated neutrophils decreased leukocyte adhesion to
      endothelial and platelet monolayers. Furthermore, rhVim blocked neutrophil
      adhesion to P-selectin-coated surfaces. Binding assays showed that rhVim binds
      specifically to P-selectin and not to its counterreceptor, PSGL-1. Finally, in an
      endotoxin model of ALI in C57BL/6J mice, treatment with rhVim significantly
      decreased histologic findings of ALI. These data suggest a potential role for
      rhVim in attenuating inflammation through blocking P-selectin-PSGL-1
      interactions.

PMID- 29335258
TI  - Cleavage of TL1A Differentially Regulates Its Effects on Innate and Adaptive
      Immune Cells.
AB  - TNF superfamily cytokines play major roles in the regulation of adaptive and
      innate immunity. The TNF superfamily cytokine TL1A (TNFSF15), through its cognate
      receptor DR3 (TNFRSF25), promotes T cell immunity to pathogens and directly
      costimulates group 2 and 3 innate lymphoid cells. Polymorphisms in the TNFSF15
      gene are associated with the risk for various human diseases, including
      inflammatory bowel disease. Like other cytokines in the TNF superfamily, TL1A is
      synthesized as a type II transmembrane protein and cleaved from the plasma
      membrane by metalloproteinases. Membrane cleavage has been shown to alter or
      abrogate certain activities of other TNF family cytokines; however, the
      functional capabilities of membrane-bound and soluble forms TL1A are not known.
      Constitutive expression of TL1A in transgenic mice results in expansion of
      activated T cells and promotes intestinal hyperplasia and inflammation through
      stimulation of group 2 innate lymphoid cells. Through the generation of membrane
      restricted TL1A-transgenic mice, we demonstrate that membrane TL1A promotes
      expression of inflammatory cytokines in the lung, dependent upon DR3 expression
      on T cells. Soluble TL1A alone was unable to produce this phenotype but was still
      able to induce intestinal type 2 inflammation independently of T cells. These
      data suggest differential roles for membrane and soluble TL1A on adaptive and
      innate immune cells and have implications for the consequences of blocking these
      two forms of TL1A.

PMID- 29335259
TI  - Mental health needs our attention.

PMID- 29335260
TI  - An emergency response to the opioid overdose crisis in Canada: a regulated opioid
      distribution program.

PMID- 29335262
TI  - Addressing overestimation of the prevalence of depression based on self-report
      screening questionnaires.

PMID- 29335261
TI  - Childhood trajectories of peer victimization and prediction of mental health
      outcomes in midadolescence: a longitudinal population-based study.
AB  - BACKGROUND: Exposure to peer victimization is relatively common. However, little
      is known about its developmental course and its effect on impairment associated
      with mental illnesses. We aimed to identify groups of children following
      differential trajectories of peer victimization from ages 6 to 13 years and to
      examine predictive associations of these trajectories with mental health in
      adolescence. METHODS: Participants were members of the Quebec Longitudinal Study
      of Child Development, a prospective cohort of 2120 children born in 1997/98 who
      were followed until age 15 years. We included 1363 participants with self
      reported victimization from ages 6 to 13 years and data available on their mental
      health status at 15 years. RESULTS: We identified 3 trajectories of peer
      victimization. The 2 prevailing groups were participants with little or moderate
      exposure to victimization (441/1685 [26.2%] and 1000/1685 [59.3%], respectively);
      the third group (244 [14.5%]) had been chronically exposed to the most severe and
      long-lasting levels of victimization. The most severely victimized individuals
      had greater odds of reporting debilitating depressive or dysthymic symptoms (odds
      ratio [OR] 2.56, 95% confidence interval [CI] 1.27-5.17), debilitating
      generalized anxiety problems (OR 3.27, CI 1.64-6.51) and suicidality (OR 3.46, CI
      1.53-7.81) at 15 years than those exposed to the lowest levels of victimization,
      after adjustment for sex, childhood mental health, family hardship and
      victimization perpetration. The association with suicidality remained significant
      after controlling for concurrent symptoms of depression or dysthymia and
      generalized anxiety problems. INTERPRETATION: Adolescents who were most severely
      victimized by peers had an increased risk of experiencing severe symptoms
      consistent with mental health problems. Given that peer victimization
      trajectories are established early on, interventions to reduce the risk of being
      victimized should start before enrolment in the formal school system.

PMID- 29335263
TI  - Exacerbation of psychosis triggered by a synthetic cannabinoid in a 70-year-old
      woman with Parkinson disease.

PMID- 29335264
TI  - Physician burnout.

PMID- 29335265
TI  - Contact lens-related Pseudomonas aeruginosa keratitis in a 49-year-old woman.

PMID- 29335266
TI  - Urgent care access: finding solutions that match causation.

PMID- 29335268
TI  - Fertility advocates protest criminal sanctions in assisted reproduction act.

PMID- 29335267
TI  - Peripartum suicide: additional considerations.

PMID- 29335269
TI  - Family doctors call for guaranteed access to EMR data for research and quality
      improvement.

PMID- 29335270
TI  - Doctors disappointed by income sprinkling changes.

PMID- 29335271
TI  - Health and social care: What's in a name?

PMID- 29335272
TI  - Complementary Value of Cardiac Magnetic Resonance Imaging and Positron Emission
      Tomography/Computed Tomography in the Assessment of Cardiac Sarcoidosis.
AB  - BACKGROUND: Although cardiac magnetic resonance (CMR) and positron emission
      tomography (PET) detect different pathological attributes of cardiac sarcoidosis
      (CS), the complementary value of these tests has not been evaluated. Our
      objective was to determine the value of combining CMR and PET in assessing the
      likelihood of CS and guiding patient management. METHODS AND RESULTS: In this
      retrospective study, we included 107 consecutive patients referred for evaluation
      of CS by both CMR and PET. Two experienced readers blinded to all clinical data
      reviewed CMR and PET images and categorized the likelihood of CS as no (<10%),
      possible (10%-50%), probable (50%-90%), or highly probable(>90%) based on
      predefined criteria. Patient management after imaging was assessed for all
      patients and across categories of increasing CS likelihood. A final clinical
      diagnosis for each patient was assigned based on a subsequent review of all
      available imaging, clinical, and pathological data. Among 107 patients (age, 55+/
      11 years; left ventricular ejection fraction, 43+/-16%), 91 (85%) had late
      gadolinium enhancement, whereas 82 (76%) had abnormal F18-fluorodeoxyglucose
      uptake on PET, suggesting active inflammation. Among the 91 patients with
      positive late gadolinium enhancement, 60 (66%) had abnormal F18
      fluorodeoxyglucose uptake. When PET data were added to CMR, 48 (45%) patients
      were reclassified as having a higher or lower likelihood of CS, most of them
      (80%) being correctly reclassified when compared with the final diagnosis.
      Changes in immunosuppressive therapies were significantly more likely among
      patients with highly probable CS. CONCLUSIONS: Among patients with suspected CS,
      combining CMR and PET provides complementary value for estimating the likelihood
      of CS and guiding patient management.

PMID- 29335273
TI  - Establishing an Evidence-Based Method to Diagnose Cardiac Sarcoidosis: The
      Complementary Use of Cardiac Magnetic Resonance Imaging and FDG-PET.

PMID- 29335274
TI  - Doctors from overseas are missing out on dyslexia screening, researchers find.

PMID- 29335275
TI  - Interplay between ChREBP and SREBP-1c coordinates postprandial glycolysis and
      lipogenesis in livers of mice.
AB  - Lipogenesis in liver is highest in the postprandial state; insulin activates
      SREBP-1c, which transcriptionally activates genes involved in FA synthesis,
      whereas glucose activates carbohydrate-responsive element-binding protein
      (ChREBP), which activates both glycolysis and FA synthesis. Whether SREBP-1c and
      ChREBP act independently of one another is unknown. Here, we characterized mice
      with liver-specific deletion of ChREBP (L-Chrebp-/- mice). Hepatic ChREBP
      deficiency resulted in reduced mRNA levels of glycolytic and lipogenic enzymes,
      particularly in response to sucrose refeeding following fasting, a dietary
      regimen that elicits maximal lipogenesis. mRNA and protein levels of SREBP-1c, a
      master transcriptional regulator of lipogenesis, were also reduced in L-Chrebp-/-
      livers. Adeno-associated virus-mediated restoration of nuclear SREBP-1c in L
      Chrebp-/- mice normalized expression of a subset of lipogenic genes, while not
      affecting glycolytic genes. Conversely, ChREBP overexpression alone failed to
      support expression of lipogenic genes in the livers of mice lacking active SREBPs
      as a result of Scap deficiency. Together, these data show that SREBP-1c and
      ChREBP are both required for coordinated induction of glycolytic and lipogenic
      mRNAs. Whereas SREBP-1c mediates insulin's induction of lipogenic genes, ChREBP
      mediates glucose's induction of both glycolytic and lipogenic genes. These
      overlapping, but distinct, actions ensure that the liver synthesizes FAs only
      when insulin and carbohydrates are both present.

PMID- 29335277
TI  - Adverse effects of caffeinated energy drinks among youth and young adults in
      Canada: a Web-based survey.
AB  - BACKGROUND: Energy drink consumption has increased dramatically among young
      Canadians, with anecdotal evidence of adverse health effects. There is a lack of
      population-based studies to examine the prevalence of adverse events from energy
      drinks, particularly among young people. The current study sought to assess
      adverse events from energy drinks among a population-based sample of youth and
      young adults in Canada. METHODS: An online survey was conducted in 2015 with a
      national sample of youth (aged 12-17 yr) and young adults (aged 18-24 yr)
      recruited from a consumer panel. Respondents reported prior consumption of energy
      drinks as well as adverse outcomes, concurrent activities associated with the
      outcomes and whether medical attention was sought or considered. Adverse events
      from coffee were also assessed for comparison. Weighted analyses are reported.
      RESULTS: Of the 2055 respondents, 1516 (73.8%) reported having ever consumed an
      energy drink, and 1741 (84.7%) reported having ever consumed coffee (unweighted).
      Overall, 55.4% of respondents who had ever consumed an energy drink reported that
      they had experienced at least 1 adverse event, including fast heartbeat (24.7%),
      difficulty sleeping (24.1%), headache (18.3%), nausea/vomiting/diarrhea (5.1%),
      chest pain (3.6%) and seizures (0.2%); 3.1% had sought or had considered seeking
      medical help for an adverse event. The prevalence of reported adverse events was
      significantly greater among energy drink consumers than among coffee consumers
      (36.0%) (odds ratio [OR] 2.67 [95% confidence interval (CI) 2.01-2.56]), as was
      the proportion who reported seeking or considering seeking medical help for
      adverse events (3.1% v. 1.4%) (OR 2.18 [95% CI 1.39-3.41]). INTERPRETATION: More
      than half of youth and young adults who had consumed energy drinks reported
      adverse outcomes, some serious enough to warrant seeking medical help. The
      adverse outcomes were consistent with the physiologic effects of caffeine but
      were significantly more prevalent than with other sources of caffeine such as
      coffee, consistent with data from national adverse event databases.

PMID- 29335278
TI  - Coffee consumption and health: we need randomised controlled trials.

PMID- 29335276
TI  - Assigning function to natural allelic variation via dynamic modeling of gene
      network induction.
AB  - More and more natural DNA variants are being linked to physiological traits. Yet,
      understanding what differences they make on molecular regulations remains
      challenging. Important properties of gene regulatory networks can be captured by
      computational models. If model parameters can be "personalized" according to the
      genotype, their variation may then reveal how DNA variants operate in the
      network. Here, we combined experiments and computations to visualize natural
      alleles of the yeast GAL3 gene in a space of model parameters describing the
      galactose response network. Alleles altering the activation of Gal3p by galactose
      were discriminated from those affecting its activity (production/degradation or
      efficiency of the activated protein). The approach allowed us to correctly
      predict that a non-synonymous SNP would change the binding affinity of Gal3p with
      the Gal80p transcriptional repressor. Our results illustrate how personalizing
      gene regulatory models can be used for the mechanistic interpretation of genetic
      variants.

PMID- 29335279
TI  - Margaret McCartney: We need another vote.

PMID- 29335282
TI  - Treatment of Subclinical Atrial Fibrillation: Does One Plus One Always Equal Two?

PMID- 29335283
TI  - Confusion Around Therapeutic Temperature Management Hypothermia After In-Hospital
      Cardiac Arrest?

PMID- 29335284
TI  - Nitric Oxide Signaling and Atherothrombosis Redux: Evidence From Experiments of
      Nature and Implications for Therapy.

PMID- 29335280
TI  - Mapping protein interactions of sodium channel NaV1.7 using epitope-tagged gene
      targeted mice.
AB  - The voltage-gated sodium channel NaV1.7 plays a critical role in pain pathways.
      We generated an epitope-tagged NaV1.7 mouse that showed normal pain behaviours to
      identify channel-interacting proteins. Analysis of NaV1.7 complexes affinity
      purified under native conditions by mass spectrometry revealed 267 proteins
      associated with Nav1.7 in vivo The sodium channel beta3 (Scn3b), rather than the
      beta1 subunit, complexes with Nav1.7, and we demonstrate an interaction between
      collapsing-response mediator protein (Crmp2) and Nav1.7, through which the
      analgesic drug lacosamide regulates Nav1.7 current density. Novel NaV1.7 protein
      interactors including membrane-trafficking protein synaptotagmin-2 (Syt2), L-type
      amino acid transporter 1 (Lat1) and transmembrane P24-trafficking protein 10
      (Tmed10) together with Scn3b and Crmp2 were validated by co-immunoprecipitation
      (Co-IP) from sensory neuron extract. Nav1.7, known to regulate opioid receptor
      efficacy, interacts with the G protein-regulated inducer of neurite outgrowth
      (Gprin1), an opioid receptor-binding protein, demonstrating a physical and
      functional link between Nav1.7 and opioid signalling. Further information on
      physiological interactions provided with this normal epitope-tagged mouse should
      provide useful insights into the many functions now associated with the NaV1.7
      channel.

PMID- 29335281
TI  - High-throughput identification of RNA nuclear enrichment sequences.
AB  - In the post-genomic era, thousands of putative noncoding regulatory regions have
      been identified, such as enhancers, promoters, long noncoding RNAs (lncRNAs), and
      a cadre of small peptides. These ever-growing catalogs require high-throughput
      assays to test their functionality at scale. Massively parallel reporter assays
      have greatly enhanced the understanding of noncoding DNA elements en masse Here,
      we present a massively parallel RNA assay (MPRNA) that can assay 10,000 or more
      RNA segments for RNA-based functionality. We applied MPRNA to identify RNA-based
      nuclear localization domains harbored in lncRNAs. We examined a pool of 11,969
      oligos densely tiling 38 human lncRNAs that were fused to a cytosolic transcript.
      After cell fractionation and barcode sequencing, we identified 109 unique RNA
      regions that significantly enriched this cytosolic transcript in the nucleus
      including a cytosine-rich motif. These nuclear enrichment sequences are highly
      conserved and over-represented in global nuclear fractionation sequencing.
      Importantly, many of these regions were independently validated by single
      molecule RNA fluorescence in situ hybridization. Overall, we demonstrate the
      utility of MPRNA for future investigation of RNA-based functionalities.

PMID- 29335285
TI  - Sodium and Potassium Intake in US Adults.

PMID- 29335286
TI  - Biomarker-Assisted Diagnosis of Acute Aortic Dissection.

PMID- 29335287
TI  - Identifying Candidates for Advanced Hemodynamic Support After Cardiac Arrest.

PMID- 29335289
TI  - Costly Medications Add Urgency to Physician-Patient Affordability Discussions.

PMID- 29335290
TI  - Young Male With Incessantly Wide Complex Tachycardia: What Is the Substrate of
      the Arrhythmia?

PMID- 29335288
TI  - Prognostic Value of High-Sensitivity Troponin T in Chronic Heart Failure: An
      Individual Patient Data Meta-Analysis.
AB  - BACKGROUND: Most patients with chronic heart failure have detectable troponin
      concentrations when evaluated by high-sensitivity assays. The prognostic
      relevance of this finding has not been clearly established so far. We aimed to
      assess high-sensitivity troponin assay for risk stratification in chronic heart
      failure through a meta-analysis approach. METHODS: Medline, EMBASE, Cochrane
      Library, and Scopus were searched in April 2017 by 2 independent authors. The
      terms were "troponin" AND "heart failure" OR "cardiac failure" OR "cardiac
      dysfunction" OR "cardiac insufficiency" OR "left ventricular dysfunction."
      Inclusion criteria were English language, clinical stability, use of a high
      sensitivity troponin assay, follow-up studies, and availability of individual
      patient data after request to authors. Data retrieved from articles and provided
      by authors were used in agreement with the PRISMA statement. The end points were
      all-cause death, cardiovascular death, and hospitalization for cardiovascular
      cause. RESULTS: Ten studies were included, reporting data on 11 cohorts and 9289
      patients (age 66+/-12 years, 77% men, 60% ischemic heart failure, 85% with left
      ventricular ejection fraction <40%). High-sensitivity troponin T data were
      available for all patients, whereas only 209 patients also had high-sensitivity
      troponin I assayed. When added to a prognostic model including established risk
      markers (sex, age, ischemic versus nonischemic etiology, left ventricular
      ejection fraction, estimated glomerular filtration rate, and N-terminal fraction
      of pro-B-type natriuretic peptide), high-sensitivity troponin T remained
      independently associated with all-cause mortality (hazard ratio, 1.48; 95%
      confidence interval, 1.41-1.55), cardiovascular mortality (hazard ratio, 1.40;
      95% confidence interval, 1.33-1.48), and cardiovascular hospitalization (hazard
      ratio, 1.42; 95% confidence interval, 1.36-1.49), over a median 2.4-year follow
      up (all P<0.001). High-sensitivity troponin T significantly improved risk
      prediction when added to a prognostic model including the variables above. It
      also displayed an independent prognostic value for all outcomes in almost all
      population subgroups. The area under the curve-derived 18 ng/L cutoff yielded
      independent prognostic value for the 3 end points in both men and women, patients
      with either ischemic or nonischemic etiology, and across categories of renal
      dysfunction. CONCLUSIONS: In chronic heart failure, high-sensitivity troponin T
      is a strong and independent predictor of all-cause and cardiovascular mortality,
      and of hospitalization for cardiovascular causes, as well. This biomarker then
      represents an additional tool for prognostic stratification.

PMID- 29335292
TI  - Letter by Madias Regarding Article, "Prosthetic Valve Endocarditis After Surgical
      Aortic Valve Replacement".

PMID- 29335291
TI  - Electronic Cigarette Smoking Increases Arterial Stiffness and Oxidative Stress to
      a Lesser Extent Than a Single Conventional Cigarette: An Acute and Chronic Study.

PMID- 29335293
TI  - Response by Glaser et al to Letter Regarding Article, "Prosthetic Valve
      Endocarditis After Surgical Aortic Valve Replacement".

PMID- 29335294
TI  - Letter by Jin-shan and Xue-bin Regarding Article, "Prospective Study of Adenosine
      on Atrioventricular Nodal Conduction in Pediatric and Young Adult Patients After
      Heart Transplantation".

PMID- 29335295
TI  - Letter by Ye et al Regarding Article, "Prospective Study of Adenosine on
      Atrioventricular Nodal Conduction in Pediatric and Young Adult Patients After
      Heart Transplantation".

PMID- 29335296
TI  - Digital healthcare: regulating the revolution.

PMID- 29335297
TI  - The apps attempting to transfer NHS 111 online.

PMID- 29335298
TI  - Crystal structure of IspF from Bacillus subtilis and absence of protein complex
      assembly amongst IspD/IspE/IspF enzymes in the MEP pathway.
AB  - 2-C-Methyl-d-erythritol 2,4-cyclodiphosphate synthase (IspF) is a key enzyme in
      the 2-C-Methyl-d-erythritol-4-phosphate (MEP) pathway of isoprenoid biosynthesis.
      This enzyme catalyzes the 4-diphosphocytidyl-2-C-methyl-d-erythritol 2-phosphate
      (CDPME2P) to 2-C-methyl-d-erythritol 2,4-cyclodiphosphate (MEcDP) with
      concomitant release of cytidine 5'-diphospate (CMP). Bacillus subtilis is a
      potential host cell for the production of isoprenoids, but few studies are
      performed on the key enzymes of MEP pathway in B. subtilis In this work, the high
      resolution crystal structures of IspF in native and complex with CMP from B.
      subtilis have been determined. Structural comparisons indicate that there is a
      looser packing of the subunits of IspF in B. subtilis, whereas the solvent
      accessible surface of its active pockets is smaller than that in Escherichia
      coli. Meanwhile, the protein-protein associations of 2-C-Methyl-d-erythritol-4
      phosphatecytidyltransferase (IspD), CDPME kinase (IspE) and IspF from B. subtilis
      and E. coli, which catalyze three consecutive steps in the MEP pathway, are
      analyzed by native gel shift and size exclusion chromatography methods. The data
      here show that protein complex assembly is not detectable. These results will be
      useful for isoprenoid biosynthesis by metabolic engineering.

PMID- 29335299
TI  - HOTAIR contributes to cell proliferation and metastasis of cervical cancer via
      targetting miR-23b/MAPK1 axis.
AB  - The long non-coding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR) has been
      found to be overexpressed in many human malignancies and involved in tumor
      progression and metastasis. Although the downstream target through which HOTAIR
      modulates tumor metastasis is not well-known, evidence suggests that miR-23b
      might be involved in this event. In the present study, the expressions of HOTAIR
      and miR-23b were detected by real-time PCR in 33 paired cervical cancer tissue
      samples and cervical cell lines. The effects of HOTAIR on the expressions of miR
      23b and mitogen-activated protein kinase 1 (MAPK1) were studied by overexpression
      and RNAi approaches. We found that HOTAIR expression was significantly increased
      in cervical cancer cells and tissues. In contrast, the expression of miR-23b was
      obviously decreased. We further demonstrated that HOTAIR knockdown promoted
      apoptosis and inhibited cell proliferation and invasion in vitro and in vivo
      Moreover, our data indicated that HOTAIR may competitively bind miR-23b and
      modulate the expression of MAPK1 indirectly in cervical cancer cells. Taken
      together, our study has identified a novel pathway through which HOTAIR exerts
      its oncogenic role, and provided a molecular basis for potential applications of
      HOTAIR in the prognosis and treatment of cervical cancer.

PMID- 29335303
TI  - Trump administration allows states to deny Medicaid to unemployed people.

PMID- 29335301
TI  - Mobilization of a splicing factor through a nuclear kinase-kinase complex.
AB  - The splicing of mRNA is dependent on serine-arginine (SR) proteins that are
      mobilized from membrane-free, nuclear speckles to the nucleoplasm by the Cdc2
      like kinases (CLKs). This movement is critical for SR protein-dependent assembly
      of the macromolecular spliceosome. Although CLK1 facilitates such trafficking
      through the phosphorylation of serine-proline dipeptides in the prototype SR
      protein SRSF1, an unrelated enzyme known as SR protein kinase 1 (SRPK1) performs
      the same function but does not efficiently modify these dipeptides in SRSF1. We
      now show that the ability of SRPK1 to mobilize SRSF1 from speckles to the
      nucleoplasm is dependent on active CLK1. Diffusion from speckles is promoted by
      the formation of an SRPK1-CLK1 complex that facilitates dissociation of SRSF1
      from CLK1 and enhances the phosphorylation of several serine-proline dipeptides
      in this SR protein. Down-regulation of either kinase blocks EGF-stimulated
      mobilization of nuclear SRSF1. These findings establish a signaling pathway that
      connects SRPKs to SR protein activation through the associated CLK family of
      kinases.

PMID- 29335300
TI  - Extracellular ATP activates store-operated Ca2+ entry in white adipocytes:
      functional evidence for STIM1 and ORAI1.
AB  - In the present study, we have applied ratiometric measurements of intracellular
      Ca2+ concentrations ([Ca2+]i) to show that extracellularly applied ATP (adenosine
      triphosphate) (100 uM) stimulates store-operated Ca2+ entry (SOCE) in 3T3-L1
      adipocytes. ATP produced a rapid increase in [Ca2+]i consisting of an initial
      transient elevation followed by a sustained elevated phase that could be observed
      only in the presence of extracellular Ca2+ Gene expression data and [Ca2+]i
      recordings with uridine-5'-triphosphate or with the phospholipase C (PLC)
      inhibitor U73122 demonstrated the involvement of purinergic P2Y2 receptors and
      the PLC/inositol trisphosphate pathway. The [Ca2+]i elevation produced by
      reintroduction of a Ca2+-containing intracellular solution to adipocytes exposed
      to ATP in the absence of Ca2+ was diminished by known SOCE antagonists. The chief
      molecular components of SOCE, the stromal interaction molecule 1 (STIM1) and the
      calcium release-activated calcium channel protein 1 (ORAI1), were detected at the
      mRNA and protein level. Moreover, SOCE was largely diminished in cells where
      STIM1 and/or ORAI1 had been silenced by small interfering (si)RNA. We conclude
      that extracellular ATP activates SOCE in white adipocytes, an effect
      predominantly mediated by STIM1 and ORAI1.

PMID- 29335304
TI  - Differentiating between acute heart failure and acute respiratory distress
      syndrome.

PMID- 29335305
TI  - Orolingual and abdominal angioedema post thrombolysis and thrombectomy.

PMID- 29335307
TI  - Editors' note: A phase 3 trial of IV immunoglobulin for Alzheimer disease.

PMID- 29335306
TI  - Pearls & Oy-sters: Family history of Huntington disease disguised a case of
      dentatorubral-pallidoluysian atrophy.

PMID- 29335308
TI  - Reader response: A phase 3 trial of IV immunoglobulin for Alzheimer disease.

PMID- 29335309
TI  - Author response: A phase 3 trial of IV immunoglobulin for Alzheimer disease.

PMID- 29335310
TI  - Editors' note: Clinical Reasoning: Labyrinthine hemorrhage: An unusual etiology
      for peripheral vertigo.

PMID- 29335311
TI  - Reader response: Clinical Reasoning: Labyrinthine hemorrhage: An unusual etiology
      for peripheral vertigo.

PMID- 29335312
TI  - Author response: Clinical Reasoning: Labyrinthine hemorrhage: An unusual etiology
      for peripheral vertigo.

PMID- 29335313
TI  - Teaching NeuroImages: Gasperini syndrome.

PMID- 29335314
TI  - Teaching Video NeuroImages: Electromyographic variation in stiff-person syndrome.

PMID- 29335315
TI  - Teaching Video NeuroImages: Oculogyric crisis in treated Parkinson disease.

PMID- 29335316
TI  - Integrated lipid clinics for adults and children with familial
      hypercholesterolaemia.

PMID- 29335317
TI  - Reduced N-Type Ca2+ Channels in Atrioventricular Ganglion Neurons Are Involved in
      Ventricular Arrhythmogenesis.
AB  - BACKGROUND: Attenuated cardiac vagal activity is associated with ventricular
      arrhythmogenesis and related mortality in patients with chronic heart failure.
      Our recent study has shown that expression of N-type Ca2+ channel alpha-subunits
      (Cav2.2-alpha) and N-type Ca2+ currents are reduced in intracardiac ganglion
      neurons from rats with chronic heart failure. Rat intracardiac ganglia are
      divided into the atrioventricular ganglion (AVG) and sinoatrial ganglion.
      Ventricular myocardium receives projection of neuronal terminals only from the
      AVG. In this study we tested whether a decrease in N-type Ca2+ channels in AVG
      neurons contributes to ventricular arrhythmogenesis. METHODS AND RESULTS:
      Lentiviral Cav2.2-alpha shRNA (2 MUL, 2*107 pfu/mL) or scrambled shRNA was in
      vivo transfected into rat AVG neurons. Nontransfected sham rats served as
      controls. Using real-time single-cell polymerase chain reaction and reverse-phase
      protein array, we found that in vivo transfection of Cav2.2-alpha shRNA decreased
      expression of Cav2.2-alpha mRNA and protein in rat AVG neurons. Whole-cell patch
      clamp data showed that Cav2.2-alpha shRNA reduced N-type Ca2+ currents and cell
      excitability in AVG neurons. The data from telemetry electrocardiographic
      recording demonstrated that 83% (5 out of 6) of conscious rats with Cav2.2-alpha
      shRNA transfection had premature ventricular contractions (P<0.05 versus 0% of
      nontransfected sham rats or scrambled shRNA-transfected rats). Additionally, an
      index of susceptibility to ventricular arrhythmias, inducibility of ventricular
      arrhythmias evoked by programmed electrical stimulation, was higher in rats with
      Cav2.2-alpha shRNA transfection compared with nontransfected sham rats and
      scrambled shRNA-transfected rats. CONCLUSIONS: A decrease in N-type Ca2+ channels
      in AVG neurons attenuates vagal control of ventricular myocardium, thereby
      initiating ventricular arrhythmias.

PMID- 29335318
TI  - Longitudinal Effect of Stroke on Cognition: A Systematic Review.
AB  - BACKGROUND: Stroke is associated with an increased risk of dementia; however, the
      impact of stroke on cognition has been found to be variable, such that stroke
      survivors can show decline, remain stable, or revert to baseline cognitive
      functioning. Knowing the natural history of cognitive impairment after stroke is
      important for intervention. The aim of this systematic review is to investigate
      the longitudinal course of cognitive function in stroke survivors. METHODS AND
      RESULTS: Three electronic databases (Medline, Embase, PsycINFO) were searched
      using OvidSP from inception to July 15, 2016. Longitudinal studies with >=2 time
      points of cognitive assessment after stroke were included. In total, 5952
      articles were retrieved and 14 were included. There was a trend toward
      significant deterioration in cognitive test scores in stroke survivors (8
      studies). Cognitive stability (3 studies) and improvement (3 studies) were also
      demonstrated, although follow-up time tended to be shorter in these studies.
      Variables associated with impairment included age, ethnicity, premorbid cognitive
      performance, depression, stroke location, and history of previous stroke.
      Associations with APOE*E4 (apolipoprotein E with the E4 allele) allele status and
      sex were mixed. CONCLUSIONS: Stroke is associated with an increased risk of
      cognitive decline, but cognitive decline is not a consequence. Factors associated
      with decline, such as sociodemographic status, health-related comorbidity, stroke
      history, and clinical features could be used in models to predict future risk of
      dementia after stroke. A risk model approach could identify patients at greatest
      risk for timely intervention to reduce the frequency or delay the onset of
      poststroke cognitive impairment and dementia.

PMID- 29335320
TI  - January 15th Question.

PMID- 29335319
TI  - Preterm Delivery and Future Risk of Maternal Cardiovascular Disease: A Systematic
      Review and Meta-Analysis.
AB  - BACKGROUND: Preterm delivery (<37 weeks gestational age) affects 11% of all
      pregnancies, but data are conflicting whether preterm birth is associated with
      long-term adverse maternal cardiovascular outcomes. We aimed to systematically
      evaluate and summarize the evidence on the relationship between preterm birth and
      future maternal risk of cardiovascular diseases. METHODS AND RESULTS: A
      systematic search of MEDLINE and EMBASE was performed to identify relevant
      studies that evaluated the association between preterm birth and future maternal
      risk of composite cardiovascular disease, coronary heart disease, stroke, and
      death caused by cardiovascular or coronary heart disease and stroke. We
      quantified the associations using random effects meta-analysis. Twenty-one
      studies with over 5.8 million women, including over 338 000 women with previous
      preterm deliveries, were identified. Meta-analysis of studies that adjusted for
      potential confounders showed that preterm birth was associated with an increased
      risk of maternal future cardiovascular disease (risk ratio [RR] 1.43, 95%
      confidence interval [CI], 1.18, 1.72), cardiovascular disease death (RR 1.78, 95%
      CI, 1.42, 2.21), coronary heart disease (RR 1.49, 95% CI, 1.38, 1.60), coronary
      heart disease death (RR 2.10, 95% CI, 1.87, 2.36), and stroke (RR 1.65, 95% CI,
      1.51, 1.79). Sensitivity analysis showed that the highest risks occurred when the
      preterm deliveries occurred before 32 weeks gestation or were medically
      indicated. CONCLUSIONS: Preterm delivery is associated with an increase in future
      maternal adverse cardiovascular outcomes, including a 2-fold increase in deaths
      caused by coronary heart disease. These findings support the assessment of
      preterm delivery in cardiovascular risk assessment in women.

PMID- 29335321
TI  - Effectiveness and Cost of Weekly Recombinant Tissue Plasminogen Activator
      Hemodialysis Catheter Locking Solution.
AB  - BACKGROUND AND OBJECTIVES: Evidence to guide hemodialysis catheter locking
      solutions is limited. We aimed to assess effectiveness and cost of recombinant
      tissue plasminogen activator (rt-PA) once per week as a locking solution,
      compared with thrice weekly citrate or heparin, in patients at high risk of
      complications. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We used a
      prospective design and pre-post comparison in three sites across Canada. Pre-post
      comparisons were conducted using multilevel mixed effects regression models
      accounting for cluster with site and potential enrollment of patients more than
      once. In the pre period, catheter malfunction was managed as per site-specific
      standard of care. The intervention in the post period was once weekly rt-PA as a
      locking solution (with citrate or heparin used for other sessions). The primary
      outcome was rate of rt-PA use for treatment of catheter malfunction. Secondary
      outcomes included rates of bacteremia, management of catheter malfunction, and
      cost. RESULTS: There were 374 patients (mean age 68 years; 52% men) corresponding
      to 506 enrollments. Mean length of enrollment was 200 days (SD 119) in the pre
      period and 187 days (SD 101) in the post period. There was a significant decline
      in rate of rt-PA use for treatment of catheter malfunction in the post compared
      with pre period (adjusted incidence rate ratio, 0.39; 95% confidence interval,
      0.30 to 0.52); however, there was no difference in the rate of bacteremia, or
      catheter stripping or removal/replacement. The increase in mean total health care
      cost in the post period was CAD$962 per enrollment, largely related to costs of
      rt-PA as a locking solution. CONCLUSIONS: Once weekly rt-PA as a catheter locking
      solution was associated with a reduction in rt-PA use for treatment of catheter
      malfunction. Our results showing a reduction in rescue rt-PA use are consistent
      with a prior randomized trial, although we did not observe a reduction in
      bacteremia or catheter stripping/removal and did observe an increased incremental
      cost of this strategy primarily accounted for by the cost of the rt-PA.

PMID- 29335322
TI  - Identifying patterns of communication in patients attending memory clinics: a
      systematic review of observations and signs with potential diagnostic utility.
AB  - BACKGROUND: Subjective cognitive complaints are commonly encountered in primary
      care and often result in memory clinic referral. However, meta-analyses have
      shown that such concerns do not consistently correspond to objective memory
      impairment or predict future dementia. Memory clinic referrals are increasing,
      with greater proportions of patients attending who do not have dementia. Studies
      of interaction during memory clinic assessments have identified conversational
      profiles that can differentiate between dementia and functional disorders of
      memory. To date, studies exploring communication patterns for the purpose of
      diagnosis have not been reviewed. Such profiles could reduce unnecessary
      investigations in patients without dementia. AIM: To identify and collate signs
      and observable features of communication, which could clinically differentiate
      between dementia and functional disorders of memory. DESIGN AND SETTING: This was
      a systematic review and synthesis of evidence from studies with heterogeneous
      methodologies. METHOD: A qualitative, narrative description and typical memory
      clinic assessment were employed as a framework. RESULTS: Sixteen studies met the
      criteria for selection. Two overarching themes emerged: 1) observable clues to
      incapacity and cognitive impairment during routine assessment and interaction,
      and 2) strategies and accounts for loss of abilities in people with dementia.
      CONCLUSION: Whether the patient attends with a companion, how they participate,
      give autobiographical history, demonstrate working memory, and make qualitative
      observations during routine cognitive testing are all useful in building a
      diagnostic picture. Future studies should explore these phenomena in larger
      populations, over longer periods, include dementia subtypes, and develop robust
      definitions of functional memory disorders to facilitate comparison.

PMID- 29335323
TI  - Antibiotic prescribing quality for children in primary care: an observational
      study.
AB  - BACKGROUND: Overuse and inappropriate prescribing of antibiotics is driving
      antibiotic resistance. GPs often prescribe antibiotics for upper respiratory
      tract infections (URTIs) in young children despite their marginal beneficial
      effects. AIM: To assess the quality of antibiotic prescribing for common
      infections in young children attending primary care and to investigate
      influencing factors. DESIGN AND SETTING: An observational, descriptive analysis,
      including children attending primary care sites in England and Wales. METHOD: The
      Diagnosis of Urinary Tract infection in Young children study collected data on
      7163 children aged <5 years, presenting to UK primary care with an acute illness
      (<28 days). Data were compared with the European Surveillance of Antimicrobial
      Consumption Network (ESAC-Net) disease-specific quality indicators to assess
      prescribing for URTIs, tonsillitis, and otitis media, against ESAC-Net proposed
      standards. Non-parametric trend tests and chi2 tests assessed trends and
      differences in prescribing by level of deprivation, site type, and demographics.
      RESULTS: Prescribing rates fell within the recommendations for URTIs but exceeded
      the recommended limits for tonsillitis and otitis media. The proportion of
      children receiving the recommended antibiotic was below standards for URTIs and
      tonsillitis, but within the recommended limits for otitis media. Prescribing
      rates increased as the level of deprivation decreased for all infections
      (P<0.05), and increased as the age of the child increased for URTIs and
      tonsillitis (P<0.05). There were no other significant trends or differences.
      CONCLUSION: The quality of antibiotic prescribing in this study was mixed and
      highlights the scope for future improvements. There is a need to assess further
      the quality of disease-specific antibiotic prescribing in UK primary care
      settings using data representative of routine clinical practice.

PMID- 29335324
TI  - Prevalence of primary aldosteronism in primary care: a cross-sectional study.
AB  - BACKGROUND: Primary aldosteronism (PA) is the most frequent cause of secondary
      hypertension. Reported prevalences of PA vary considerably because of a large
      heterogeneity in study methodology. AIM: To examine the proportion of patients
      with PA among patients with newly diagnosed, never treated hypertension. DESIGN
      AND SETTING: A cross-sectional study set in primary care. METHOD: GPs measured
      aldosterone and renin in adult patients with newly diagnosed, never treated
      hypertension. Patients with elevated aldosterone-to-renin ratio and increased
      plasma aldosterone concentration underwent a saline infusion test to confirm or
      exclude PA. The source population was meticulously assessed to detect possible
      selection bias. RESULTS: Of 3748 patients with newly diagnosed hypertension, 343
      patients were screened for PA. In nine out of 74 patients with an elevated
      aldosterone-to-renin ratio and increased plasma aldosterone concentration the
      diagnosis of PA was confirmed by a saline infusion test, resulting in a
      prevalence of 2.6% (95% confidence interval = 1.4 to 4.9). All patients with PA
      were normokalaemic and 8 out of 9 patients had sustained blood pressure >150/100
      mmHg. Screened patients were younger (P<0.001) or showed higher blood pressure
      (P<0.001) than non-screened patients. CONCLUSION: In this study a prevalence of
      PA of 2.6% in a primary care setting was established, which is lower than
      estimates reported from other primary care studies so far. This study supports
      the screening strategy as recommended by the Endocrine Society Clinical Practice
      Guideline. The low proportion of screened patients (9.2%), of the large cohort of
      eligible patients, reflects the difficulty of conducting prevalence studies in
      primary care clinical practice.

PMID- 29335325
TI  - Population and patient factors affecting emergency department attendance in
      London: retrospective cohort analysis of linked primary and secondary care
      records.
AB  - BACKGROUND: Population factors, including social deprivation and morbidity,
      predict the use of emergency departments (EDs). AIM: To link patient-level
      primary and secondary care data to determine whether the association between
      deprivation and ED attendance is explained by multimorbidity and other clinical
      factors in the GP record. DESIGN AND SETTING: Retrospective cohort study based in
      East London. METHOD: Primary care demographic, consultation, diagnostic, and
      clinical data were linked with ED attendance data. GP Patient Survey (GPPS)
      access questions were linked to practices. RESULTS: Adjusted multilevel analysis
      for adults showed a progressive rise in ED attendance with increasing numbers of
      long-term conditions (LTCs). Comparing two LTCs with no conditions, the odds
      ratio (OR) is 1.28 (95% confidence interval [CI] = 1.25 to 1.31); comparing four
      or more conditions with no conditions, the OR is 2.55 (95% CI = 2.44 to 2.66).
      Increasing annual GP consultations predicted ED attendance: comparing zero with
      more than two consultations, the OR is 2.44 (95% CI = 2.40 to 2.48). Smoking (OR
      1.30, 95% CI = 1.28 to 1.32), being housebound (OR 2.01, 95% CI = 1.86 to 2.18),
      and age also predicted attendance. Patient-reported access scores from the GPPS
      were not a significant predictor. For children, younger age, male sex, white
      ethnicity, and higher GP consultation rates predicted attendance. CONCLUSION:
      Using patient-level data rather than practice-level data, the authors demonstrate
      that the burden of multimorbidity is the strongest clinical predictor of ED
      attendance, which is independently associated with social deprivation. Low use of
      the GP surgery is associated with low attendance at ED. Unlike other studies, the
      authors found that adult patient experience of GP access, reported at practice
      level, did not predict use.

PMID- 29335326
TI  - Attendance of routine childcare visits in primary care for children of mothers
      with depression: a nationwide population-based cohort study.
AB  - BACKGROUND: Depression is a common and potentially debilitating illness
      worldwide. Attendance to routine childcare appointments is a key point of
      interest in the effort to improve the health and care for families facing
      depression. AIM: To evaluate the association between maternal depression and
      offspring non-attendance to the Danish childcare and vaccination programme (CCP)
      for children from 0-5 years of age. The CCP consists of seven separate visits and
      several vaccinations. To investigate if exposure to recent and previous
      depression may affect attendance differently. DESIGN AND SETTING: Population
      based cohort study using Danish nationwide registers. METHOD: Participants were
      all live-born children (n = 853 315) in Denmark in the period from 1 January 2000
      until 31 August 2013, and their mothers. The outcome of interest was non
      attendance of each one of the seven scheduled childcare visits and two
      vaccination entities in the CCP. Exposure was maternal (both previous and recent)
      depression. All information was obtained from Danish national registries.
      RESULTS: The risk of not attending CCP was higher for children of mothers with
      depression. For children of mothers with previous depression, the relative risk
      (RR) was 1.01 (95% confidence interval [CI] = 0.98 to 1.03) at the 5-week
      childcare visit, and 1.12 (95% CI = 1.09 to 1.14) at the 5-year childcare visit.
      For children of mothers with recent depression, the RR was 1.07 (95% CI = 1.03 to
      1.13) at the 5-week visit, and 1.15 (95% CI = 1.13 to 1.17) at the 5-year visit.
      Furthermore, the risk of missing at least four of the seven childcare visits was
      higher for children of females with maternal depression (RR = 1.16, 95% CI = 1.13
      to 1.19). CONCLUSION: Maternal depression seems to compromise CCP attendance.
      These findings suggest a need for careful clinical attention to these vulnerable
      families, even years after a diagnosis of depression.

PMID- 29335327
TI  - GPs' experiences of diagnosing and managing childhood eczema: a qualitative study
      in primary care.
AB  - BACKGROUND: Eczema is common among children, and in the UK the majority are
      managed by GPs. The most common cause of poor disease control is incorrect use of
      topical treatments. There is a lack of research into the challenges faced by GPs
      in diagnosing and managing this condition. AIM: To explore the experiences of GPs
      in assessing and managing children with eczema. DESIGN AND SETTING: Qualitative
      study in primary care in England. METHOD: Semi-structured interviews with 15 GPs
      were audiorecorded, transcribed verbatim, and analysed thematically using the
      framework method. RESULTS: GPs described a paucity of dermatology training.
      Although most GPs were confident diagnosing uncomplicated eczema, they reported
      using a trial-and-error approach to prescribing emollients, and were uncertain
      about quantities of topical treatments to issue. Mild and moderate potency
      topical corticosteroids (TCS) were commonly used, but most GPs lacked confidence
      in recommending potent TCS, and viewed parents or carers to be fearful of using
      all strengths of TCS. GPs perceived adherence to treatments to be low, but
      provision of information to support self-care was variable. Routine review of
      medication use or disease control was uncommon, which GPs attributed to service
      constraints. Participants' views on the causes and management of eczema were
      perceived to be at odds with parents and carers, who were said to be overly
      focused on an underlying cause, such as allergy. CONCLUSION: GP uncertainty in
      managing eczema, lack of routine information and review, and perceived dissonance
      with parents around causation and management may be contributing to low
      concordance with treatments.

PMID- 29335328
TI  - Walking prescription of 10 000 steps per day in patients with type 2 diabetes
      mellitus: a randomised trial in Nigerian general practice.
AB  - BACKGROUND: In clinical practice, translating the benefits of a sustained
      physically active lifestyle on glycaemic control in patients with type 2 diabetes
      mellitus (T2DM) is difficult. A walking prescription may be an effective
      alternative. AIM: To examine the effect of a 10 000 steps per day prescription on
      glycaemic control of patients with T2DM. DESIGN AND SETTING: Forty-six adults
      with T2DM attending a general outpatient clinic were randomised into two equal
      groups. The intervention group was given goals to accumulate 10 000 steps per day
      for 10 weeks, whereas the control group maintained their normal activity habits.
      METHOD: Daily step count was measured with waist-mounted pedometer and baseline
      and endline average steps per day. Glycosylated haemoglobin (HbA1c),
      anthropometric, and cardiovascular measurements were also obtained. An intention
      to-treat analysis was done. RESULTS: The average baseline step count was 4505
      steps per day for all participants, and the average step count in the
      intervention group for the last 4 weeks of the study period was higher by 2913
      steps per day (95% confidence interval [CI] = 1274 to 4551, F (2, 37.7) = 18.90,
      P<0.001). Only 6.1% of the intervention group participants achieved the 10 000
      steps per day goal. The mean baseline HbA1c was 6.6% (range = 5.3 to 9.0).
      Endline HbA1c was lower in the intervention group than in the control group (mean
      difference -0.74%, 95% CI = -1.32 to -0.02, F = 12.92, P = 0.015) after adjusting
      for baseline HbA1c. There was no change in anthropometric and cardiovascular
      indices. CONCLUSION: Adherence to 10 000 steps per day prescription is low but
      may still be associated with improved glycaemic control in T2DM. Motivational
      strategies for better adherence would improve glycaemic control.

PMID- 29335329
TI  - Relocating patients from a specialist homeless healthcare centre to general
      practices: a multi-perspective study.
AB  - BACKGROUND: The relocation of formerly homeless patients eligible to transfer
      from a specialist homeless healthcare centre (SHHC) to mainstream general
      practices is key to patient integration in the local community. Failure to
      transition patients conferring eligibility for relocation may also negatively
      impact on SHHC service delivery. AIM: To explore barriers and facilitators of
      relocation from the perspectives of formerly homeless patients and healthcare
      staff involved in their care. DESIGN AND SETTING: Qualitative semi-structured
      face-to-face and telephone interviews conducted in the north east of Scotland.
      METHOD: Participants were patients and healthcare staff including GPs, nurses,
      substance misuse workers, administrative, and local community pharmacy staff
      recruited from one SHHC, two mainstream general practices, and four community
      pharmacies. Interview schedules based on the 14 domains of the Theoretical
      Domains Framework (TDF) were drafted. Transcripts of the interviews were analysed
      by two independent researchers using a framework approach. RESULTS: Seventeen
      patients and 19 staff participated. Key barriers and facilitators aligned to TDF
      domains included: beliefs about consequences regarding relocation; patient
      intention to relocate; environmental context and resources in relation to the
      care of the patients and assessing patient eligibility; patient skills in
      relation to integration; social and professional role and identity of staff and
      patients; and emotional attachment to the SHHC. CONCLUSION: Implementation of
      services, which promote relocation and integration, may optimise patient
      relocation from SHHCs to mainstream general practices. These include peer support
      networks for patients, better information provision on the relocation process,
      and supporting patients in the journey of identifying and adjusting to mainstream
      practices.

PMID- 29335330
TI  - Stroke Incidence and Outcomes in Northeastern Greece: The Evros Stroke Registry.
AB  - BACKGROUND AND PURPOSE: Data are scarce on both stroke incidence rates and
      outcomes in Greece and in rural areas in particular. We performed a prospective
      population-based study evaluating the incidence of first-ever stroke in the Evros
      prefecture, a region of a total 147 947 residents located in North Eastern
      Greece. METHODS: Adult patients with first-ever stroke were registered during a
      24-month period (2010-2012) and followed up for 12 months. To compare our stroke
      incidence with that observed in other studies, we standardized our incidence rate
      data according to the European Standard Population, World Health Organization,
      and Segi population. We also applied criteria of data quality proposed by the
      Monitoring Trends and Determinants in Cardiovascular Disease project. Stroke
      diagnosis and classification were performed using World Health Organization
      criteria on the basis of neuroimaging and autopsy data. RESULTS: We prospectively
      documented 703 stroke cases (mean age: 75+/-12 years; 52.8% men; ischemic stroke:
      80.8%; intracerebral hemorrhage: 11.8%; subarachnoid hemorrhage: 4.4%; undefined:
      3.0%) with a total follow-up time of 119 805 person-years. The unadjusted and
      European Standard Population-adjusted incidences of all strokes were 586.8 (95%
      confidence interval [CI], 543.4-630.2) and 534.1 (95% CI, 494.6-573.6) per 100
      000 person-years, respectively. The unadjusted incidence rates for ischemic
      stroke, intracerebral hemorrhage, and subarachnoid hemorrhage were 474.1 (95% CI,
      435-513), 69.3 (95% CI, 54-84), and 25.9 (95% CI, 17-35) per 100 000 person
      years, respectively. The corresponding European Standard Population-adjusted
      incidence rates per 100 000 person-years were 425.9 (95% CI, 390.9-460.9), 63.3
      (95% CI, 49.7-76.9), and 25.8 (95% CI, 16.7-34.9) for ischemic stroke,
      intracerebral hemorrhage, and subarachnoid hemorrhage, respectively. The overall
      28-day case fatality rate was 21.3% (95% CI, 18.3%-24.4%) for all strokes and was
      higher in hemorrhagic strokes than ischemic stroke (40.4%, 95% CI, 31.3%-49.4%
      versus 16.2%, 95% CI, 13.2%-19.2%). CONCLUSIONS: This is the largest to date
      population-based study in Greece documenting one of the highest stroke incidences
      ever reported in South Europe, highlighting the need for efficient stroke
      prevention and treatment strategies in Northeastern Greece.

PMID- 29335332
TI  - Historical Slavery and Modern-Day Stroke Mortality in the United States Stroke
      Belt.

PMID- 29335331
TI  - Cerebrovascular Disease Knowledge Portal: An Open-Access Data Resource to
      Accelerate Genomic Discoveries in Stroke.

PMID- 29335333
TI  - Predictors of In-Hospital Death After Aneurysmal Subarachnoid Hemorrhage:
      Analysis of a Nationwide Database (Swiss SOS [Swiss Study on Aneurysmal
      Subarachnoid Hemorrhage]).
AB  - BACKGROUND AND PURPOSE: To identify predictors of in-hospital mortality in
      patients with aneurysmal subarachnoid hemorrhage and to estimate their impact.
      METHODS: Retrospective analysis of prospective data from a nationwide multicenter
      registry on all aneurysmal subarachnoid hemorrhage cases admitted to a tertiary
      neurosurgical department in Switzerland (Swiss SOS [Swiss Study on Aneurysmal
      Subarachnoid Hemorrhage]; 2009-2015). Both clinical and radiological independent
      predictors of in-hospital mortality were identified, and their effect size was
      determined by calculating adjusted odds ratios (aORs) using multivariate logistic
      regression. Survival was displayed using Kaplan-Meier curves. RESULTS: Data of
      n=1866 aneurysmal subarachnoid hemorrhage patients in the Swiss SOS database were
      available. In-hospital mortality was 20% (n=373). In n=197 patients (10.6%),
      active treatment was discontinued after hospital admission (no aneurysm occlusion
      attempted), and this cohort was excluded from analysis of the main statistical
      model. In the remaining n=1669 patients, the rate of in-hospital mortality was
      13.9% (n=232). Strong independent predictors of in-hospital mortality were
      rebleeding (aOR, 7.69; 95% confidence interval, 3.00-19.71; P<0.001), cerebral
      infarction attributable to delayed cerebral ischemia (aOR, 3.66; 95% confidence
      interval, 1.94-6.89; P<0.001), intraventricular hemorrhage (aOR, 2.65; 95%
      confidence interval, 1.38-5.09; P=0.003), and new infarction post-treatment (aOR,
      2.57; 95% confidence interval, 1.43-4.62; P=0.002). CONCLUSIONS: Several-and
      among them modifiable-factors seem to be associated with in-hospital mortality
      after aneurysmal subarachnoid hemorrhage. Our data suggest that strategies aiming
      to reduce the risk of rebleeding are most promising in patients where active
      treatment is initially pursued. CLINICAL TRIAL REGISTRATION: URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT03245866.

PMID- 29335334
TI  - Diagnosis of Cerebral Amyloid Angiopathy: Evolution of the Boston Criteria.

PMID- 29335335
TI  - Closure of Patent Foramen Ovale Versus Medical Therapy in Patients With
      Cryptogenic Stroke or Transient Ischemic Attack: Updated Systematic Review and
      Meta-Analysis.
AB  - BACKGROUND AND PURPOSE: Previous systematic reviews and meta-analyses compared
      the efficacy and safety of patent foramen ovale (PFO) closure versus medical
      treatment in patients with cryptogenic stroke or transient ischemic attack (TIA).
      Recently, new evidence from randomized trials became available. METHODS: We
      searched PubMed until September 24, 2017, for trials comparing PFO closure with
      medical treatment in patients with cryptogenic stroke/TIA using the items: stroke
      or cerebrovascular accident or TIA and patent foramen ovale or paradoxical
      embolism and trial or study. RESULTS: Among 851 identified articles, 5 were
      eligible. In 3627 patients with 3.7-year mean follow-up, there was significant
      difference in ischemic stroke recurrence (0.53 versus 1.1 per 100 patient-years,
      respectively; odds ratio [OR], 0.43; 95% confidence intervals (CI), 0.21-0.90;
      relative risk reduction, 50.5%; absolute risk reduction, 2.11%; and number needed
      to treat to prevent 1 event, 46.5 for 3.7 years). There was no significant
      difference in TIAs (0.78 versus 0.98 per 100 patient-years, respectively; OR,
      0.80; 95% CI, 0.53-1.19) and all-cause mortality (0.18 versus 0.23 per 100
      patient-years, respectively; OR, 0.73; 95% CI, 0.34-1.56). New-onset atrial
      fibrillation occurred more frequently in the PFO closure arm (1.3 versus 0.25 per
      100 patient-years, respectively; OR, 5.15; 95% CI, 2.18-12.15) and resolved in
      72% of cases within 45 days, whereas rates of myocardial infarction (0.12 versus
      0.09 per 100 patient-years, respectively; OR, 1.22; 95% CI, 0.25-5.91) and any
      serious adverse events (7.3 versus 7.3 per 100 patient-years, respectively; OR,
      1.07; 95% CI, 0.92-1.25) were similar. CONCLUSIONS: In patients with cryptogenic
      stroke/TIA and PFO who have their PFO closed, ischemic stroke recurrence is less
      frequent compared with patients receiving medical treatment. Atrial fibrillation
      is more frequent but mostly transient. There is no difference in TIA, all-cause
      mortality, or myocardial infarction.

PMID- 29335336
TI  - Periodontal Disease, Regular Dental Care Use, and Incident Ischemic Stroke.
AB  - BACKGROUND AND PURPOSE: Periodontal disease is independently associated with
      cardiovascular disease. Identification of periodontal disease as a risk factor
      for incident ischemic stroke raises the possibility that regular dental care
      utilization may reduce the stroke risk. METHODS: In the ARIC (Atherosclerosis
      Risk in Communities) study, pattern of dental visits were classified as regular
      or episodic dental care users. In the ancillary dental ARIC study, selected
      subjects from ARIC underwent fullmouth periodontal measurements collected at 6
      sites per tooth and classified into 7 periodontal profile classes (PPCs).
      RESULTS: In the ARIC study 10 362 stroke-free participants, 584 participants had
      incident ischemic strokes over a 15-year period. In the dental ARIC study, 6736
      dentate subjects were assessed for periodontal disease status using PPC with a
      total of 299 incident ischemic strokes over the 15-year period. The 7 levels of
      PPC showed a trend toward an increased stroke risk (chi2 trend P<0.0001); the
      incidence rate for ischemic stroke/1000-person years was 1.29 for PPC-A (health),
      2.82 for PPC-B, 4.80 for PPC-C, 3.81 for PPC-D, 3.50 for PPC-E, 4.78 for PPC-F,
      and 5.03 for PPC-G (severe periodontal disease). Periodontal disease was
      significantly associated with cardioembolic (hazard ratio, 2.6; 95% confidence
      interval, 1.2-5.6) and thrombotic (hazard ratio, 2.2; 95% confidence interval,
      1.3-3.8) stroke subtypes. Regular dental care utilization was associated with
      lower adjusted stroke risk (hazard ratio, 0.77; 95% confidence interval, 0.63
      0.94). CONCLUSIONS: We confirm an independent association between periodontal
      disease and incident stroke risk, particularly cardioembolic and thrombotic
      stroke subtype. Further, we report that regular dental care utilization may lower
      this risk for stroke.

PMID- 29335337
TI  - Salivary glands regenerate after radiation injury through SOX2-mediated secretory
      cell replacement.
AB  - Salivary gland acinar cells are routinely destroyed during radiation treatment
      for head and neck cancer that results in a lifetime of hyposalivation and co
      morbidities. A potential regenerative strategy for replacing injured tissue is
      the reactivation of endogenous stem cells by targeted therapeutics. However, the
      identity of these cells, whether they are capable of regenerating the tissue, and
      the mechanisms by which they are regulated are unknown. Using in vivo and ex vivo
      models, in combination with genetic lineage tracing and human tissue, we discover
      a SOX2+ stem cell population essential to acinar cell maintenance that is capable
      of replenishing acini after radiation. Furthermore, we show that acinar cell
      replacement is nerve dependent and that addition of a muscarinic mimetic is
      sufficient to drive regeneration. Moreover, we show that SOX2 is diminished in
      irradiated human salivary gland, along with parasympathetic nerves, suggesting
      that tissue degeneration is due to loss of progenitors and their regulators.
      Thus, we establish a new paradigm that salivary glands can regenerate after
      genotoxic shock and do so through a SOX2 nerve-dependent mechanism.

PMID- 29335340
TI  - Anticitrullinated Protein Antibodies Induce Inflammatory Gene Expression Profile
      in Peripheral Blood Cells from CCP-positive Patients with RA.
AB  - OBJECTIVE: Anticitrullinated protein antibodies (ACPA) have major diagnostic
      significance in rheumatoid arthritis (RA). ACPA are directed against different
      citrullinated antigens, including filaggrin, fibrinogen, vimentin, and collagen.
      The presence of ACPA is associated with joint damage and extraarticular
      manifestations, suggesting that ACPA may have a significant role in the
      pathogenesis of RA. METHODS: To verify the effect of ACPA on RA-immune cells,
      peripheral blood mononuclear cells (PBMC) from cyclic citrullinated peptide (CCP)
      positive patients with RA and healthy controls were cocultured in vitro with
      ACPA. ACPA-positive stained cells were analyzed by flow cytometry and the effect
      of ACPA on mRNA expression levels was evaluated by real-time PCR. We tested
      whether the stimulatory effects induced by ACPA could be inhibited by the
      addition of a new multiepitope citrullinated peptide (Cit-ME). RESULTS: We found
      that ACPA bind specifically to PBMC from CCP-positive patients with RA through
      the Fab portion. ACPA induce upregulation of pathogenic cytokine expression (4-
      to 13-fold increase) in PBMC derived from CCP-positive patients with RA.
      Moreover, ACPA upregulated IL-1beta and IL-6 mRNA expression levels by 10- and 6
      fold, respectively, compared to control IgG. Cit-ME, a genuine ligand of ACPA,
      inhibited the ACPA-induced upregulation of IL-1beta and IL-6 by 30%. CONCLUSION:
      ACPA bind to a limited percentage of PBMC and upregulate inflammatory cytokine
      expression, suggesting that ACPA is involved in RA pathogenesis. Targeting ACPA
      to decrease their pathogenic effects might provide a novel direction in
      developing therapeutic strategies for RA.

PMID- 29335341
TI  - Trends in Healthcare Expenditures among Individuals with Arthritis in the United
      States from 2008 to 2014.
AB  - OBJECTIVE: With the expected rise in the arthritis population, information is
      required regarding trends of healthcare expenditures among individuals with
      arthritis in the United States. We examined temporal trends in direct and out-of
      pocket (OOP) healthcare expenditures among individuals with arthritis using a
      nationally representative database, the Medical Expenditures Panel Survey.
      METHODS: The study population was composed of cross-sectional cohorts of
      individuals aged >= 18 years from 2008 to 2014. Two-part models were used to
      estimate the incremental total and types of annual direct and OOP healthcare
      expenditures (adjusted to 2014 US dollars) for arthritis, after controlling for
      predisposing, enabling, need, personal health practice, and external
      environmental factors, as per the Anderson Healthcare Behavioral Model. RESULTS:
      An annual weighted arthritis population rose from 56.1 million in 2008 to 65.1
      million in 2014. Among individuals with arthritis, the annual average direct and
      OOP expenditure was $10,424 [standard error (SE) = $345, aggregate = $584.8
      billion] and $1493 (SE = $50, aggregate = $83.8 billion) in 2008, respectively,
      and $910 (SE = $279, total = $645.1 billion) and $1099 (SE = $36, aggregate =
      $71.5 billion) in 2014, respectively. In the fully adjusted model, individuals
      with arthritis had significantly greater total and OOP expenditures from 2008 to
      2014; however, the magnitude of incremental OOP expenditure declined from 2008 to
      2014. CONCLUSION: Although the annual direct healthcare expenditures per person
      remained stable over the years, the rise in proportion of the arthritis
      population led to a huge increase in aggregate economic burden to the US
      healthcare system.

PMID- 29335338
TI  - CRTH2 promotes endoplasmic reticulum stress-induced cardiomyocyte apoptosis
      through m-calpain.
AB  - Apoptotic death of cardiac myocytes is associated with ischemic heart disease and
      chemotherapy-induced cardiomyopathy. Chemoattractant receptor-homologous molecule
      expressed on T helper type 2 cells (CRTH2) is highly expressed in the heart.
      However, its specific role in ischemic cardiomyopathy is not fully understood.
      Here, we demonstrated that CRTH2 disruption markedly improved cardiac recovery in
      mice postmyocardial infarction and doxorubicin challenge by suppressing
      cardiomyocyte apoptosis. Mechanistically, CRTH2 activation specifically
      facilitated endoplasmic reticulum (ER) stress-induced cardiomyocyte apoptosis via
      caspase-12-dependent pathway. Blockage of m-calpain prevented CRTH2-mediated
      cardiomyocyte apoptosis under ER stress by suppressing caspase-12 activity. CRTH2
      was coupled with Galphaq to elicit intracellular Ca2+ flux and activated m
      calpain/caspase-12 cascade in cardiomyocytes. Knockdown of caspase-4, an
      alternative to caspase-12 in humans, markedly alleviated CRHT2 activation-induced
      apoptosis in human cardiomyocyte response to anoxia. Our findings revealed an
      unexpected role of CRTH2 in promoting ER stress-induced cardiomyocyte apoptosis,
      suggesting that CRTH2 inhibition has therapeutic potential for ischemic
      cardiomyopathy.

PMID- 29335339
TI  - Inhibition of Drp1/Fis1 interaction slows progression of amyotrophic lateral
      sclerosis.
AB  - Bioenergetic failure and oxidative stress are common pathological hallmarks of
      amyotrophic lateral sclerosis (ALS), but whether these could be targeted
      effectively for novel therapeutic intervention needs to be determined. One of the
      reported contributors to ALS pathology is mitochondrial dysfunction associated
      with excessive mitochondrial fission and fragmentation, which is predominantly
      mediated by Drp1 hyperactivation. Here, we determined whether inhibition of
      excessive fission by inhibiting Drp1/Fis1 interaction affects disease
      progression. We observed mitochondrial excessive fragmentation and dysfunction in
      several familial forms of ALS patient-derived fibroblasts as well as in cultured
      motor neurons expressing SOD1 mutant. In both cell models, inhibition of
      Drp1/Fis1 interaction by a selective peptide inhibitor, P110, led to a
      significant reduction in reactive oxygen species levels, and to improvement in
      mitochondrial structure and functions. Sustained treatment of mice expressing
      G93A SOD1 mutation with P110, beginning at the onset of disease symptoms at day
      90, produced an improvement in motor performance and survival, suggesting that
      Drp1 hyperactivation may be an attractive target in the treatment of ALS
      patients.

PMID- 29335342
TI  - Comparative Efficacy of Tumor Necrosis Factor-alpha Inhibitors in Ankylosing
      Spondylitis: A Systematic Review and Bayesian Network Metaanalysis.
AB  - OBJECTIVE: To compare the efficacy of 6 tumor necrosis factor-alpha inhibitors
      (TNFi) in treatment of ankylosing spondylitis (AS) at 12 weeks and 24 weeks.
      METHODS: We performed a systematic literature review of randomized controlled
      trials of TNFi in patients with active AS. We included trials that reported
      efficacy at 10 to 14 weeks (12-week analysis) and at 24 to 30 weeks (24-week
      analysis). We used Bayesian network metaanalysis (NMA) to compare their relative
      efficacy to improve the Bath Ankylosing Spondylitis Disease Activity Index
      (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), and C-reactive
      protein (CRP) level. RESULTS: We included 20 trials of 6 TNFi, with 43 treatment
      arms and 3220 participants. All TNFi were significantly better than placebo in
      reducing BASDAI and BASFI at 12 weeks and 24 weeks; all but certolizumab pegol
      (CZP) were statistically better than placebo in reducing CRP at 12 weeks; all but
      CZP and infliximab-dyyb (IFX biosimilar) were significantly better than placebo
      in reducing CRP at 24 weeks. IFX was superior to the other TNFi in decreasing
      BASDAI at 12 weeks, but not at 24 weeks. Excluding 1 open-label trial, there were
      no differences among TNFi. CONCLUSION: Based on this NMA of clinical trials, IFX
      was superior to other TNFi in reducing BASDAI at 12 weeks, but sensitive to
      inclusion of an open-label trial, and its efficacy was diminished at 24 weeks.
      The analysis was limited by few direct comparison trials. Further study of
      relative safety and longterm effectiveness will help inform the choice of TNFi in
      treating active AS.

PMID- 29335343
TI  - Association Between Glucocorticoid Exposure and Healthcare Expenditures for
      Potential Glucocorticoid-related Adverse Events in Patients with Rheumatoid
      Arthritis.
AB  - OBJECTIVE: Oral glucocorticoid (OGC) use for rheumatoid arthritis (RA) is debated
      because of the adverse event (AE) profile of OGC. We evaluated the associations
      between cumulative doses of OGC and potential OGC-related AE, and quantified the
      associated healthcare expenditures. METHODS: Using the MarketScan databases,
      patients >= 18 years old who have RA with continuous enrollment from January 1 to
      December 31, 2012 (baseline), and from January 1 to December 31, 2013 (evaluation
      period), were identified. Cumulative OGC dose was measured using prescription
      claims during the baseline period. Potential OGC-related AE (osteoporosis,
      fracture, aseptic necrosis of the bone, type 2 diabetes, ulcer/gastrointestinal
      bleeding, cataract, hospitalization for opportunistic infection, myocardial
      infarction, or stroke) and AE-related expenditures (2013 US$) were gathered
      during the evaluation period. Multivariable regression models were fitted to
      estimate OR of AE and incremental costs for patients with AE. RESULTS: There were
      84,357 patients analyzed, of whom 48% used OGC during the baseline period and 26%
      had an AE during the evaluation period. A cumulative OGC dose > 1800 mg was
      associated with an increased risk of any AE compared with no OGC exposure (OR
      1.19, 99.65% CI 1.09-1.30). Incremental costs per patient with any AE were
      significantly greater for cumulative OGC dose > 1800 mg compared with no OGC
      exposure (incremental cost = $3528, 99.65% CI $2402-$4793). CONCLUSION: Chronic
      exposure to low to medium doses of OGC was associated with significantly
      increased risk of potential OGC-related AE in patients with RA, and greater
      cumulative OGC dose was associated with substantially higher AE-related
      healthcare expenditures among patients with AE.

PMID- 29335344
TI  - Can Ultrasound Be Used to Predict Loss of Remission in Patients with RA in a Real
      life Setting? A Multicenter Cohort Study.
AB  - OBJECTIVE: Several studies have suggested that patients with rheumatoid arthritis
      (RA) presenting with ultrasound (US) synovitis despite clinical remission have
      more subsequent flares than those who show both clinical and sonographic
      remission. The objective of our study was to investigate whether these results
      could be translated to a real-life setting. METHODS: We compared the time from
      the first US performed in clinical remission to loss of remission (defined by a
      DAS28 > 2.6 or the need for stepping up treatment with disease-modifying
      antirheumatic drugs) within the Swiss Clinical Quality Management cohort of
      patients with RA, and we adjusted for relevant confounders. Analyses were
      repeated for different definitions of US-detected synovitis (US+) using
      greyscale, Doppler, and combined modes based on previously validated scores, and
      they were adjusted for relevant confounders. RESULTS: There were 318 RA patients
      with 378 remission phases included. Loss of clinical remission was observed in
      60% of remission phases. Residual US synovitis was associated with a shorter
      duration of clinical remission (median 2-5 mos) and a moderately increased hazard
      ratio (HR) for loss of remission (HR 1.2-1.5), with the highest HR for the
      combined US score. The association between US+ and loss of remission was
      strongest when the US measurement had taken place early in remission (shorter
      median duration of 6-20 mos) and when followup time was limited to the first 3 or
      6 months (most HR between 2-4). CONCLUSION: US-detected synovitis, particularly
      when US is performed early in clinical remission, has a moderate predictive power
      for loss of remission in a real-life setting.

PMID- 29335346
TI  - Severity of Sacroiliitis and Erythrocyte Sedimentation Rate are Associated with a
      Low Trabecular Bone Score in Young Male Patients with Ankylosing Spondylitis.
AB  - OBJECTIVE: To examine factors related to a low trabecular bone score (TBS) and
      the association between TBS and vertebral fractures in patients with ankylosing
      spondylitis (AS). METHODS: One hundred patients (all male, aged < 50 yrs) who
      fulfilled the modified New York criteria for the classification of AS were
      enrolled. The TBS and bone mineral density (BMD) were assessed using dual-energy
      X-ray absorptiometry. Clinical variables, inflammatory markers, and the presence
      of vertebral fractures were also assessed. Sacroiliitis grade and spinal
      structural damage were measured using the modified New York criteria and the
      Stoke Ankylosing Spondylitis Spine Score (SASSS). RESULTS: The mean TBS was 1.38
      +/- 0.13. The TBS showed a positive correlation with BMD at the lumbar spine,
      femoral neck, and total hip. TBS negatively correlated with SASSS, whereas BMD at
      the lumbar spine showed a positive correlation. A significant decrease in TBS
      values was observed in patients with spinal structural damage (p = 0.001).
      Univariate analysis identified disease duration, erythrocyte sedimentation rate
      (ESR), sacroiliitis grade, and SASSS as being associated with TBS. Multivariate
      analysis identified ESR and sacroiliitis grade as being independently associated
      with TBS (p = 0.006 and p < 0.001, respectively). Ten patients had morphometric
      vertebral fractures. The mean TBS was lower in patients with vertebral fractures
      than in age-matched patients without fractures (p = 0.028). Lower TBS predicted
      vertebral fractures (area under curve = 0.733, cutoff = 1.311). CONCLUSION: The
      TBS in young male patients with AS is associated with the ESR and severity of
      sacroiliitis. The TBS may be useful as a tool for assessing osteoporosis in AS.

PMID- 29335345
TI  - S100A12 Is Associated with Response to Therapy in Juvenile Idiopathic Arthritis.
AB  - OBJECTIVE: Around one-third of patients with juvenile idiopathic arthritis (JIA)
      fail to respond to first-line methotrexate (MTX) or anti-tumor necrosis factor
      (TNF) therapy, with even fewer achieving >= American College of Rheumatology
      Pediatric 70% criteria for response (ACRpedi70), though individual responses
      cannot yet be accurately predicted. Because change in serum S100-protein myeloid
      related protein complex 8/14 (MRP8/14) is associated with therapeutic response,
      we tested granulocyte-specific S100-protein S100A12 as a potential biomarker for
      treatment response. METHODS: S100A12 serum concentration was determined by ELISA
      in patients treated with MTX (n = 75) and anti-TNF (n = 88) at baseline and
      followup. Treatment response (>= ACRpedi50 score), achievement of inactive
      disease, and improvement in Juvenile Arthritis Disease Activity Score (JADAS)-10
      score were recorded. RESULTS: Baseline S100A12 concentration was measured in
      patients treated with anti-TNF [etanercept n = 81, adalimumab n = 7; median 200,
      interquartile range (IQR) 133-440 ng/ml] and MTX (median 220, IQR 100-440 ng/ml).
      Of the patients in the anti-TNF therapy group, 74 (84%) were also receiving MTX.
      Responders to MTX (n = 57/75) and anti-TNF (n = 66/88) therapy had higher
      baseline S100A12 concentration compared to nonresponders: median 240 (IQR 125
      615) ng/ml versus 150 (IQR 87-233) ng/ml, p = 0.021 for MTX, and median 308 (IQR
      150-624) ng/ml versus 151 (IQR 83-201) ng/ml, p = 0.002, for anti-TNF therapy.
      Followup S100A12 could be measured in 44/75 MTX-treated patients (34/44
      responders) and 39/88 anti-TNF-treated patients (26/39 responders). Responders
      had significantly reduced S100A12 concentration (MTX: p = 0.031, anti-TNF: p <
      0.001) at followup versus baseline. Baseline serum S100A12 in both univariate and
      multivariate regression models for anti-TNF therapy and univariate analysis alone
      for MTX therapy was significantly associated with change in JADAS-10. CONCLUSION:
      Responders to MTX or anti-TNF treatment can be identified by higher pretreatment
      S100A12 serum concentration levels.

PMID- 29335348
TI  - The Dorsal 4-finger Technique: A Novel Method to Examine Metacarpophalangeal
      Joints in Patients with Rheumatoid Arthritis.
AB  - OBJECTIVE: To describe the dorsal 4-finger technique (DFFT) in examining
      metacarpophalangeal (MCP) joints of patients with rheumatoid arthritis (RA) and
      compare it to the traditional 2-finger technique (TFT) using ultrasound (US) as a
      gold standard. METHODS: Four rheumatologists evaluated 180 MCP joints of 18
      patients with RA. All patients underwent US for greyscale (GSUS) and power
      Doppler US (PDUS). Agreements between rheumatologists, the 2 techniques, and US
      were evaluated using Cohen kappa and the first-order agreement coefficient (AC1)
      kappa methods. RESULTS: The population comprised 17 females (94.4%) with a mean
      (SD) age and disease duration of 56.8 (14.4) and 21.8 (12.9) years, respectively.
      Eight patients (44.4%) were taking methotrexate monotherapy, while 10 patients
      (55.6%) were receiving biologics. US evaluation revealed 69 (38.3%) and 30
      (16.7%) joints exhibited synovitis grade 2-3 by GSUS and PDUS, respectively.
      Effusion was documented in 30 joints (16.7%). The mean intraobserver agreement
      using the DFFT and TFT were 80.5% and 86%, respectively. The mean interobserver
      agreements using the DFFT and TFT were 84% and 74%, respectively. kappa agreement
      with US findings was similar for both techniques in tender joints but was higher
      for the DFFT in nontender joints (0.33 vs 0.07, p = 0.015 for GSUS) and (0.48 vs
      0.11, p = 0.002 for PDUS). The DFFT had a higher sensitivity in detecting
      ballottement by GSUS (0.47 vs 0.2, p < 0.001) and PDUS (0.60 vs 0.27, p < 0.001).
      CONCLUSION: The DFFT is a novel, reproducible, and reliable method to examine MCP
      joints, and it has a better correlation with US than the traditional TFT.

PMID- 29335347
TI  - Smoking Is the Most Significant Modifiable Lung Cancer Risk Factor in Systemic
      Lupus Erythematosus.
AB  - OBJECTIVE: To assess lung cancer risk in systemic lupus erythematosus (SLE),
      relative to demographics, drug exposures, smoking, and disease activity. METHODS:
      We analyzed data from 14 SLE cohorts. We calculated adjusted HR estimates for
      lung cancer in SLE, relative to demographics, smoking, time-dependent medication
      exposures, and cumulative disease activity [mean adjusted SLE Disease Activity
      Index (SLEDAI) scores]. This project was approved by the ethics boards of all
      participating institutions, including the Institutional Review Board of the
      McGill University Health Centre. The ethics approval number for the Cancer Risk
      study is GEN-06-031. RESULTS: Within these 14 SLE cohorts, 49 incident lung
      cancers occurred. Among lung cancer cases, 59.0% were in the highest SLEDAI
      quartile at baseline versus 40.8% of lung cancer-free SLE controls. The vast
      majority (84.2%) of SLE lung cancer cases were ever-smokers at baseline, versus
      40.1% of those without lung cancer. In adjusted models, the principal factors
      associated with lung cancer were ever smoking (at cohort entry) and current age.
      Estimated adjusted effects of all drugs were relatively imprecise, but did not
      point toward any drug exposures as strong lung cancer risk factors. CONCLUSION:
      We saw no clear evidence for drugs as a trigger for lung cancer risk in SLE,
      although drug risk estimates were relatively imprecise. Smoking may be the most
      significant modifiable lung cancer risk factor in SLE.

PMID- 29335349
TI  - Efficacy of Continuous Interleukin 1 Blockade in Mevalonate Kinase Deficiency: A
      Multicenter Retrospective Study in 13 Adult Patients and Literature Review.
AB  - OBJECTIVE: To report efficacy and tolerance of interleukin 1 blockade in adult
      patients with mevalonate kinase deficiency (MKD). METHODS: We retrospectively
      collected data on 13 patients with MKD who had received anakinra (n = 10) and
      canakinumab (n = 7). RESULTS: Anakinra resulted in complete or partial remission
      in 3/10 and 5/10 patients, respectively, and no efficacy in 2/10, but a switch to
      canakinumab led to partial remission. Canakinumab resulted in complete or partial
      remission in 3/7 and 4/7 patients, respectively. CONCLUSION: These data support
      frequent partial responses, showing a better response with canakinumab. The
      genotype and therapeutic outcomes correlation should help in the personalization
      of treatment.

PMID- 29335351
TI  - Endocrinologist charged with murder of wife who threatened to reveal his opioid
      dealing.

PMID- 29335350
TI  - Epidemiology and Medication Pattern Change of Psoriatic Diseases in Taiwan from
      2000 to 2013: A Nationwide, Population-based Cohort Study.
AB  - OBJECTIVE: To analyze the trend of prevalence and incidence rates for psoriatic
      arthritis (PsA) and psoriasis in Taiwan, and to determine the changes in
      medication patterns. METHODS: Data were collected from the Taiwan National Health
      Insurance Research Database, which covered at least 95% of the population from
      2000 to 2013. International Classification of Diseases, 9th edition (ICD-9) was
      used to identify PsA (ICD-9 696.0) and other psoriasis (ICD-9 696.1). Medications
      were identified by Anatomical Therapeutic Chemical Classification code. We
      calculated the annual age standardized prevalence and incidence rate of PsA and
      psoriasis in individuals aged >= 16 years from 2000 to 2013, and used the Poisson
      regression to test the trends by Wald chi-square statistic. RESULTS: The
      prevalence (per 100,000 population) of psoriatic diseases between 2000 and 2013
      increased from 11.12 to 37.75 for PsA, and from 179.2 to 281.5 for psoriasis. The
      incidence (per 100,000 person-yrs) increased from 3.64 to 6.91 in PsA, while
      there was no significant change in psoriasis. Prevalence and incidence in PsA
      were more rapidly increased than in psoriasis. Sex ratio (men to women) of PsA
      decreased from 2.0 to 1.5 in 2000 and 2013, respectively. There was an increase
      in the use of disease-modifying antirheumatic drugs (DMARD), especially
      biologics, which is significantly different from topical therapies. CONCLUSION:
      The prevalence and incidence rates of psoriatic disease, especially PsA, were
      increasing in Taiwan. The medication pattern showed an increase in DMARD and
      biologics, while use of topical therapies decreased.

PMID- 29335352
TI  - Discrete Modules and Mesoscale Functional Circuits for Thermal Nociception within
      Primate S1 Cortex.
AB  - This study addresses one long-standing question of whether functional separations
      are preserved for somatosensory modalities of touch, heat, and cold nociception
      within primate primary somatosensory (S1) cortex. This information is critical
      for understanding how the nature of pain is represented in the primate brain.
      Using a combination of submillimeter-resolution fMRI and microelectrode local
      field potential (LFP) and spike recordings, we identified spatially segregated
      cortical zones for processing touch and nociceptive heat and cold stimuli in
      somatotopically appropriate areas 3a, 3b, 1, and 2 of S1 in male monkeys. The
      distances between zones were comparable (~3.4 mm) across stimulus modalities
      (heat, cold, and tactile), indicating the existence of uniform, modality-specific
      modules. Stimulus-evoked LFP maps validated the fMRI maps in areas 3b and 1.
      Isolation of heat and cold nociceptive neurons from the fMRI zones confirmed the
      validity of using fMRI to probe nociceptive regions and circuits. Resting-state
      fMRI analysis revealed distinct intrinsic functional circuits among functionally
      related zones. We discovered distinct modular structures and networks for thermal
      nociception within S1 cortex, a finding that has significant implications for
      studying chronic pain syndromes and guiding the selection of neuromodulation
      targets for chronic pain management.SIGNIFICANCE STATEMENT Primate S1 subregions
      contain discrete heat and cold nociceptive modules. Modules with the same
      properties exhibit strong functional connection. Nociceptive fMRI response
      coincides with LFP and spike activities of nociceptive neurons. Functional
      separation of heat and cold pain is retained within primate S1 cortex.

PMID- 29335353
TI  - KChIP3 N-Terminal 31-50 Fragment Mediates Its Association with TRPV1 and
      Alleviates Inflammatory Hyperalgesia in Rats.
AB  - Potassium voltage-gated channel interacting protein 3 (KChIP3), also termed
      downstream regulatory element antagonist modulator (DREAM) and calsenilin, is a
      multifunctional protein belonging to the neuronal calcium sensor (NCS) family.
      Recent studies revealed the expression of KChIP3 in dorsal root ganglion (DRG)
      neurons, suggesting the potential role of KChIP3 in peripheral sensory
      processing. Herein, we show that KChIP3 colocalizes with transient receptor
      potential ion channel V1 (TRPV1), a critical molecule involved in peripheral
      sensitization during inflammatory pain. Furthermore, the N-terminal 31-50
      fragment of KChIP3 is capable of binding both the intracellular N and C termini
      of TRPV1, which substantially decreases the surface localization of TRPV1 and the
      subsequent Ca2+ influx through the channel. Importantly, intrathecal
      administration of the transmembrane peptide transactivator of transcription (TAT)
      31-50 remarkably reduces Ca2+ influx via TRPV1 in DRG neurons and alleviates
      thermal hyperalgesia and gait alterations in a complete Freund's adjuvant-induced
      inflammatory pain model in male rats. Moreover, intraplantar injection of TAT-31
      50 attenuated the capsaicin-evoked spontaneous pain behavior and thermal
      hyperalgesia, which further strengthened the regulatory role of TAT-31-50 on
      TRPV1 channel. In addition, TAT-31-50 could also alleviate inflammatory thermal
      hyperalgesia in kcnip3-/- rats generated in our study, suggesting that the
      analgesic effect mediated by TAT-31-50 is independent of endogenous KChIP3. Our
      study reveals a novel peripheral mechanism for the analgesic function of KChIP3
      and provides a potential analgesic agent, TAT-31-50, for the treatment of
      inflammatory pain.SIGNIFICANCE STATEMENT Inflammatory pain arising from inflamed
      or injured tissues significantly compromises the quality of life in patients.
      This study aims to elucidate the role of peripheral potassium channel interacting
      protein 3 (KChIP3) in inflammatory pain. Direct interaction of the KChIP3 N
      terminal 31-50 fragment with transient receptor potential ion channel V1 (TRPV1)
      was demonstrated. The KChIP3-TRPV1 interaction reduces the surface localization
      of TRPV1 and thus alleviates heat hyperalgesia and gait alterations induced by
      peripheral inflammation. Furthermore, the transmembrane transactivator of
      transcription (TAT)-31-50 peptide showed analgesic effects on inflammatory
      hyperalgesia independently of endogenous KChIP3. This work reveals a novel
      mechanism of peripheral KChIP3 in inflammatory hyperalgesia that is distinct from
      its classical role as a transcriptional repressor in pain modulation.

PMID- 29335354
TI  - Correction: Heat strain, volume depletion and kidney function in California
      agricultural workers.

PMID- 29335355
TI  - Snap, crackle and pop: when sneezing leads to crackling in the neck.
AB  - Spontaneous perforation of the pharynx is an unusual condition. Due to its non
      specific presentation and general lack of awareness, diagnosis and intervention
      may be delayed resulting in potential complications. This case reports a rare
      spontaneous perforation of the pyriform sinus after a forceful sneeze, leading to
      cervical subcutaneous emphysema and pneumomediastinum.

PMID- 29335356
TI  - Single Bursts of Individual Granule Cells Functionally Rearrange Feedforward
      Inhibition.
AB  - The sparse single-spike activity of dentate gyrus granule cells (DG GCs) is
      punctuated by occasional brief bursts of 3-7 action potentials. It is well-known
      that such presynaptic bursts in individual mossy fibers (MFs; axons of granule
      cells) are often able to discharge postsynaptic CA3 pyramidal cells due to
      powerful short-term facilitation. However, what happens in the CA3 network after
      the passage of a brief MF burst, before the arrival of the next burst or solitary
      spike, is not understood. Because MFs innervate significantly more CA3
      interneurons than pyramidal cells, we focused on unitary MF responses in
      identified interneurons in the seconds-long postburst period, using paired
      recordings in rat hippocampal slices. Single bursts as short as 5 spikes in <30
      ms in individual presynaptic MFs caused a sustained, large increase (tripling) in
      the amplitude of the unitary MF-EPSCs for several seconds in ivy, axo
      axonic/chandelier and basket interneurons. The postburst unitary MF-EPSCs in
      these feedforward interneurons reached amplitudes that were even larger than the
      MF-EPSCs during the bursts in the same cells. In contrast, no comparable
      postburst enhancement of MF-EPSCs could be observed in pyramidal cells or
      nonfeedforward interneurons. The robust postburst increase in MF-EPSCs in
      feedforward interneurons was associated with significant shortening of the
      unitary synaptic delay and large downstream increases in disynaptic IPSCs in
      pyramidal cells. These results reveal a new cell type-specific plasticity that
      enables even solitary brief bursts in single GCs to powerfully enhance inhibition
      at the DG-CA3 interface in the seconds-long time-scales of interburst
      intervals.SIGNIFICANCE STATEMENT The hippocampal formation is a brain region that
      plays key roles in spatial navigation and learning and memory. The first stage of
      information processing occurs in the dentate gyrus, where principal cells are
      remarkably quiet, discharging low-frequency single action potentials interspersed
      with occasional brief bursts of spikes. Such bursts, in particular, have
      attracted a lot of attention because they appear to be critical for efficient
      coding, storage, and recall of information. We show that single bursts of a few
      spikes in individual granule cells result in seconds-long potentiation of
      excitatory inputs to downstream interneurons. Thus, while it has been known that
      bursts powerfully discharge ("detonate") hippocampal excitatory cells, this study
      clarifies that they also regulate inhibition during the interburst intervals.

PMID- 29335357
TI  - Nonlinear Relationship Between Spike-Dependent Calcium Influx and TRPC Channel
      Activation Enables Robust Persistent Spiking in Neurons of the Anterior Cingulate
      Cortex.
AB  - Continuation of spiking after a stimulus ends (i.e. persistent spiking) is
      thought to support working memory. Muscarinic receptor activation enables
      persistent spiking among synaptically isolated pyramidal neurons in anterior
      cingulate cortex (ACC), but a detailed characterization of that spiking is
      lacking and the underlying mechanisms remain unclear. Here, we show that the rate
      of persistent spiking in ACC neurons is insensitive to the intensity and number
      of triggers, but can be modulated by injected current, and that persistent
      spiking can resume after several seconds of hyperpolarization-imposed quiescence.
      Using electrophysiology and calcium imaging in brain slices from male rats, we
      determined that canonical transient receptor potential (TRPC) channels are
      necessary for persistent spiking and that TRPC-activating calcium enters in a
      spike-dependent manner via voltage-gated calcium channels. Constrained by these
      biophysical details, we built a computational model that reproduced the observed
      pattern of persistent spiking. Nonlinear dynamical analysis of that model
      revealed that TRPC channels become fully activated by the small rise in
      intracellular calcium caused by evoked spikes. Calcium continues to rise during
      persistent spiking, but because TRPC channel activation saturates, firing rate
      stabilizes. By calcium rising higher than required for maximal TRPC channel
      activation, TRPC channels are able to remain active during periods of
      hyperpolarization-imposed quiescence (until calcium drops below saturating
      levels) such that persistent spiking can resume when hyperpolarization is
      discontinued. Our results thus reveal that the robust intrinsic bistability
      exhibited by ACC neurons emerges from the nonlinear positive feedback
      relationship between spike-dependent calcium influx and TRPC channel
      activation.SIGNIFICANCE STATEMENT Neurons use action potentials, or spikes, to
      encode information. Some neurons can store information for short periods (seconds
      to minutes) by continuing to spike after a stimulus ends, thus enabling working
      memory. This so-called "persistent" spiking occurs in many brain areas and has
      been linked to activation of canonical transient receptor potential (TRPC)
      channels. However, TRPC activation alone is insufficient to explain many aspects
      of persistent spiking such as resumption of spiking after periods of imposed
      quiescence. Using experiments and simulations, we show that calcium influx caused
      by spiking is necessary and sufficient to activate TRPC channels and that the
      ensuing positive feedback interaction between intracellular calcium and TRPC
      channel activation can account for many hitherto unexplained aspects of
      persistent spiking.

PMID- 29335358
TI  - Sox2 Is Essential for Oligodendroglial Proliferation and Differentiation during
      Postnatal Brain Myelination and CNS Remyelination.
AB  - In the CNS, myelination and remyelination depend on the successful progression
      and maturation of oligodendroglial lineage cells, including proliferation and
      differentiation of oligodendroglial progenitor cells (OPCs). Previous studies
      have reported that Sox2 transiently regulates oligodendrocyte (OL)
      differentiation in the embryonic and perinatal spinal cord and appears
      dispensable for myelination in the postnatal spinal cord. However, the role of
      Sox2 in OL development in the brain has yet to be defined. We now report that
      Sox2 is an essential positive regulator of developmental myelination in the
      postnatal murine brain of both sexes. Stage-specific paradigms of genetic
      disruption demonstrated that Sox2 regulated brain myelination by coordinating
      upstream OPC population supply and downstream OL differentiation. Transcriptomic
      analyses further supported a crucial role of Sox2 in brain developmental
      myelination. Consistently, oligodendroglial Sox2-deficient mice developed severe
      tremors and ataxia, typical phenotypes indicative of hypomyelination, and
      displayed severe impairment of motor function and prominent deficits of brain OL
      differentiation and myelination persisting into the later CNS developmental
      stages. We also found that Sox2 was required for efficient OPC proliferation and
      expansion and OL regeneration during remyelination in the adult brain and spinal
      cord. Together, our genetic evidence reveals an essential role of Sox2 in brain
      myelination and CNS remyelination, and suggests that manipulation of Sox2 and/or
      Sox2-mediated downstream pathways may be therapeutic in promoting CNS myelin
      repair.SIGNIFICANCE STATEMENT Promoting myelin formation and repair has
      translational significance in treating myelin-related neurological disorders,
      such as periventricular leukomalacia and multiple sclerosis in which brain
      developmental myelin formation and myelin repair are severely affected,
      respectively. In this report, analyses of a series of genetic conditional knock
      out systems targeting different oligodendrocyte stages reveal a previously
      unappreciated role of Sox2 in coordinating upstream proliferation and downstream
      differentiation of oligodendroglial lineage cells in the mouse brain during
      developmental myelination and CNS remyelination. Our study points to the
      potential of manipulating Sox2 and its downstream pathways to promote
      oligodendrocyte regeneration and CNS myelin repair.

PMID- 29335359
TI  - Recruitment of Additional Corticospinal Pathways in the Human Brain with State
      Dependent Paired Associative Stimulation.
AB  - Standard brain stimulation protocols modify human motor cortex excitability by
      modulating the gain of the activated corticospinal pathways. However, the
      restoration of motor function following lesions of the corticospinal tract
      requires also the recruitment of additional neurons to increase the net
      corticospinal output. For this purpose, we investigated a novel protocol based on
      brain state-dependent paired associative stimulation.Motor imagery (MI)-related
      electroencephalography was recorded in healthy males and females for brain state
      dependent control of both cortical and peripheral stimulation in a brain-machine
      interface environment. State-dependency was investigated with concurrent,
      delayed, and independent stimulation relative to the MI task. Specifically,
      sensorimotor event-related desynchronization (ERD) in the beta-band (16-22 Hz)
      triggered peripheral stimulation through passive hand opening by a robotic
      orthosis and transcranial magnetic stimulation to the respective cortical motor
      representation, either synchronously or subsequently. These MI-related paradigms
      were compared with paired cortical and peripheral input applied independent of
      the brain state. Cortical stimulation resulted in a significant increase in
      corticospinal excitability only when applied brain state-dependently and
      synchronously to peripheral input. These gains were resistant to a depotentiation
      task, revealed a nonlinear evolution of plasticity, and were mediated via the
      recruitment of additional corticospinal neurons rather than via synchronization
      of neuronal firing. Recruitment of additional corticospinal pathways may be
      achieved when cortical and peripheral inputs are applied concurrently, and during
      beta-ERD. These findings resemble a gating mechanism and are potentially
      important for developing closed-loop brain stimulation for the treatment of hand
      paralysis following lesions of the corticospinal tract.SIGNIFICANCE STATEMENT The
      activity state of the motor system influences the excitability of corticospinal
      pathways to external input. State-dependent interventions harness this property
      to increase the connectivity between motor cortex and muscles. These stimulation
      protocols modulate the gain of the activated pathways, but not the overall
      corticospinal recruitment. In this study, a brain-machine interface paired
      peripheral stimulation through passive hand opening with transcranial magnetic
      stimulation to the respective cortical motor representation during volitional
      beta-band desynchronization. Cortical stimulation resulted in the recruitment of
      additional corticospinal pathways, but only when applied brain state-dependently
      and synchronously to peripheral input. These effects resemble a gating mechanism
      and may be important for the restoration of motor function following lesions of
      the corticospinal tract.

PMID- 29335361
TI  - Correction to "Discovery of Novel Small-Molecule Inducers of Heme Oxygenase-1
      That Protect Human iPSC-Derived Cardiomyocytes from Oxidative Stress".

PMID- 29335360
TI  - Activity in the Ventral Medial Prefrontal Cortex Is Necessary for the Therapeutic
      Effects of Extinction in Rats.
AB  - Poor response and high relapse rates remain problematic in the treatment of
      stress-related psychiatric disorders such as depression and post-traumatic stress
      disorder. Although mechanisms of pharmacotherapies are intensely studied, little
      is known about mechanisms of behavioral therapy that could inform improved
      treatments. We have previously demonstrated the therapeutic effects of extinction
      learning as a behavioral intervention modeling exposure therapy in rats. In the
      present study, we tested the hypothesis that activity in the ventral medial
      prefrontal cortex (vmPFC) during extinction is necessary for its therapeutic
      effects. The inhibitory Gi-coupled designer receptor exclusively activated by
      designer drug CaMKIIalpha-hM4Di was expressed in vmPFC before administering
      chronic unpredictable stress (CUS). vmPFC projection neurons were then inhibited
      during extinction treatment by administering clozapine-N-oxide. Coping behavior
      and cognitive flexibility were assessed 24 h later on the shock-probe defensive
      burying test and attentional set-shifting test, respectively. Replicating
      previous results, extinction reversed the CUS-induced deficits in coping behavior
      and cognitive flexibility. Inhibiting vmPFC during extinction blocked these
      therapeutic effects. Further, increasing vmPFC activity with the excitatory Gq
      coupled designer receptor exclusively activated by designer drug hM3Dq 24 h
      before testing was sufficient to reverse the CUS-induced deficits. CUS reduced
      mPFC responsivity, assessed by measuring afferent-evoked field potentials in the
      mPFC, and this reduction was reversed by extinction treatment 24 h before
      testing. These results demonstrate the necessity of vmPFC activity in the
      therapeutic effects of extinction as a model of exposure therapy, and suggest
      that increased vmPFC activity induced by extinction is sufficient to produce
      lasting plastic changes that underlie its beneficial effects.SIGNIFICANCE
      STATEMENT Stress-related psychiatric disorders remain poorly treated.
      Psychotherapies can be effective, but their mechanisms remain unknown, hindering
      progress toward improved treatment. We used a rat model of behavioral therapy to
      identify potential targets for enhancing treatment. Fear extinction as a
      therapeutic behavioral intervention reversed stress-induced cognitive dysfunction
      and passive coping in rats, modeling components of stress-related psychiatric
      disease. Extinction also reversed stress-induced attenuation of mPFC
      responsivity. The therapeutic effects were prevented by blocking activity of
      glutamatergic neurons in the mPFC during extinction, and were mimicked by
      inducing activity in lieu of extinction. Thus, activity and plasticity in the
      mPFC underlie the beneficial effects of extinction on cognitive flexibility and
      coping behavior compromised by stress, and could be targets to enhance behavioral
      therapy.

PMID- 29335362
TI  - China: a return to the "kingdom of bicycles"?

PMID- 29335363
TI  - Why are there associations between telomere length and behaviour?
AB  - Individual differences in telomere length are associated with individual
      differences in behaviour in humans and birds. Within the human epidemiological
      literature this association is assumed to result from specific behaviour patterns
      causing changes in telomere dynamics. We argue that selective adoption-the
      hypothesis that individuals with short telomeres are more likely to adopt
      specific behaviours-is an alternative worthy of consideration. Selective adoption
      could occur either because telomere length directly affects behaviour or because
      behaviour and telomere length are both affected by a third variable, such as
      exposure to early-life adversity. We present differential predictions of the
      causation and selective adoption hypotheses and describe how these could be
      tested with longitudinal data on telomere length. Crucially, if behaviour is
      causal then it should be associated with differential rates of telomere
      attrition. Using smoking behaviour as an example, we show that the evidence that
      smoking accelerates the rate of telomere attrition within individuals is
      currently weak. We conclude that the selective adoption hypothesis for the
      association between behaviour and telomere length is both mechanistically
      plausible and, if anything, more compatible with existing empirical evidence than
      the hypothesis that behaviour is causal.This article is part of the theme issue
      'Understanding diversity in telomere dynamics'.

PMID- 29335364
TI  - Experimental manipulation of telomere length: does it reveal a corner-stone role
      for telomerase in the natural variability of individual fitness?
AB  - Telomeres, the non-coding ends of linear chromosomes, are thought to be an
      important mechanism of individual variability in performance. Research suggests
      that longer telomeres are indicative of better health and increased fitness;
      however, many of these data are correlational and whether these effects are
      causal are poorly understood. Experimental tests are emerging in medical and
      laboratory-based studies, but these types of experiments are rare in natural
      populations, which precludes conclusions at an evolutionary level. At the
      crossroads between telomere length and fitness is telomerase, an enzyme that can
      lengthen telomeres. Experimental modulation of telomerase activity is a powerful
      tool to manipulate telomere length, and to look at the covariation of telomerase,
      telomeres and individual life-history traits. Here, we review studies that
      manipulate telomerase activity in laboratory conditions and emphasize the
      associated physiological and fitness consequences. We then discuss how
      telomerase's impact on ageing may go beyond telomere maintenance. Based on this
      overview, we then propose several research avenues for future studies to explore
      how individual variability in health, reproduction and survival may have
      coevolved with different patterns of telomerase activity and expression. Such
      knowledge is of prime importance to fully understand the role that telomere
      dynamics play in the evolution of animal ageing.This article is part of the theme
      issue 'Understanding diversity in telomere dynamics'.

PMID- 29335365
TI  - Characterization in humans of in vitro leucocyte maximal telomerase activity
      capacity and association with stress.
AB  - The goal of this study was to develop and validate a measure of maximal
      telomerase activity capacity (mTAC) for use in human studies of telomere biology,
      and to determine its association with measures of stress and stress responsivity.
      The study was conducted in a population of 28 healthy young women and men who
      were assessed serially across two separate days, at multiple time points, and in
      response to a standardized laboratory stressor. Venous blood was collected at
      each of these multiple assessments, and an in vitro mitogen challenge
      (phytohaemagglutinin supplemented with interleukin-2) was used to stimulate
      telomerase activity in leucocytes. After first establishing the optimal post
      stimulation time course to characterize mTAC, we determined the within-subject
      stability and the between-subject variability of mTAC. The major findings of our
      study are as follows: (i) the optimal time point to quantify human leucocyte mTAC
      appears to be at 72 h after mitogen stimulation; (ii) mTAC exhibits substantial
      within-subject stability (correlations were in the range of r 0.68-0.82) and
      between-subject variability, with a high intra-class coefficient (0.70),
      indicating greater between-subject relative to within-subject variability; (iii)
      mTAC is not influenced by situational factors including time of day, cortisol,
      acute stress exposure and immune cell distribution in the pre-stimulation blood
      sample; and (iv) a significant proportion of the between-subject variability in
      mTAC is associated with measures of stress and stress responsivity (mTAC is lower
      in subjects reporting higher levels of perceived (chronic) stress and exhibiting
      higher psychophysiological stress reactivity). Based collectively on these
      findings, it appears that mTAC, as proposed and operationalized, empirically
      meets the key criteria to represent a potentially useful individual difference
      measure of telomerase activity capacity of human leucocytes.This article is part
      of the theme issue 'Understanding diversity in telomere dynamics'.

PMID- 29335367
TI  - Evolution of telomere maintenance and tumour suppressor mechanisms across
      mammals.
AB  - Mammalian species differ dramatically in telomere biology. Species larger than 5
      10 kg repress somatic telomerase activity and have shorter telomeres, leading to
      replicative senescence. It has been proposed that evolution of replicative
      senescence in large-bodied species is an anti-tumour mechanism counteracting
      increased risk of cancer due to increased cell numbers. By contrast, small-bodied
      species express high telomerase activity and have longer telomeres. To counteract
      cancer risk due to longer lifespan, long-lived small-bodied species evolved
      additional telomere-independent tumour suppressor mechanisms. Here, we tested the
      connection between telomere biology and tumorigenesis by analysing the propensity
      of fibroblasts from 18 rodent species to form tumours. We found a negative
      correlation between species lifespan and anchorage-independent growth. Small
      bodied species required inactivation of Rb and/or p53 and expression of oncogenic
      H-Ras to form tumours. Large-bodied species displayed a continuum of phenotypes
      requiring additional genetic 'hits' for malignant transformation. Based on these
      data we refine the model of the evolution of tumour suppressor mechanisms and
      telomeres. We propose that two different strategies evolved in small and large
      species because small-bodied species cannot tolerate small tumours that form
      prior to activation of the telomere barrier, and must instead use telomere
      independent strategies that act earlier, at the hyperplasia stage.This article is
      part of the theme issue 'Understanding diversity in telomere dynamics'.

PMID- 29335366
TI  - The paternal age at conception effect on offspring telomere length: mechanistic,
      comparative and adaptive perspectives.
AB  - Telomeres are repeating DNA found at the ends of chromosomes that, in the absence
      of restorative processes, shorten with cell replications and are implicated as a
      cause of senescence. It appears that sperm telomere length (TL) increases with
      age in humans, and as a result offspring of older fathers inherit longer
      telomeres. We review possible mechanisms underlying this paternal age at
      conception (PAC) effect on TL, including sperm telomere extension due to
      telomerase activity, age-dependent changes in the spermatogonial stem cell
      population (possibly driven by 'selfish' spermatogonia) and non-causal
      confounding. In contrast to the lengthening of TL with PAC, higher maternal age
      at conception appears to predict shorter offspring TL in humans. We review
      evidence for heterogeneity across species in the PAC effect on TL, which could
      relate to differences in statistical power, sperm production rates or testicular
      telomerase activity. Finally, we review the hypothesis that the PAC effect on TL
      may allow a gradual multi-generational adaptive calibration of maintenance
      effort, and reproductive lifespan, to local demographic conditions: descendants
      of males who reproduced at a later age are likely to find themselves in an
      environment where increased maintenance effort, allowing later reproduction,
      represents a fitness improving resource allocation.This article is part of the
      theme issue 'Understanding diversity in telomere dynamics'.

PMID- 29335368
TI  - In medio stat virtus: unanticipated consequences of telomere dysequilibrium.
AB  - The integrity of chromosome ends, or telomeres, depends on myriad processes that
      must balance the need to compact and protect the telomeric, G-rich DNA from
      detection as a double-stranded DNA break, and yet still permit access to enzymes
      that process, replicate and maintain a sufficient reserve of telomeric DNA. When
      unable to maintain this equilibrium, erosion of telomeres leads to perturbations
      at or near the telomeres themselves, including loss of binding by the telomere
      protective complex, shelterin, and alterations in transcription and post
      translational modifications of histones. Although the catastrophic consequences
      of full telomere de-protection are well described, recent evidence points to
      other, less obvious perturbations that arise when telomere length equilibrium is
      altered. For example, critically short telomeres also perturb DNA methylation and
      histone post-translational modifications at distal sites throughout the genome.
      In murine stem cells for example, this dysregulated chromatin leads to
      inappropriate suppression of pluripotency regulator factors such as Nanog This
      review summarizes these recent findings, with an emphasis on how these genome
      wide, telomere-induced perturbations can have profound consequences on cell
      function and fate.This article is part of the theme issue 'Understanding
      diversity in telomere dynamics'.

PMID- 29335369
TI  - The rate of telomere loss is related to maximum lifespan in birds.
AB  - Telomeres are highly conserved regions of DNA that protect the ends of linear
      chromosomes. The loss of telomeres can signal an irreversible change to a cell's
      state, including cellular senescence. Senescent cells no longer divide and can
      damage nearby healthy cells, thus potentially placing them at the crossroads of
      cancer and ageing. While the epidemiology, cellular and molecular biology of
      telomeres are well studied, a newer field exploring telomere biology in the
      context of ecology and evolution is just emerging. With work to date focusing on
      how telomere shortening relates to individual mortality, less is known about how
      telomeres relate to ageing rates across species. Here, we investigated telomere
      length in cross-sectional samples from 19 bird species to determine how rates of
      telomere loss relate to interspecific variation in maximum lifespan. We found
      that bird species with longer lifespans lose fewer telomeric repeats each year
      compared with species with shorter lifespans. In addition, phylogenetic analysis
      revealed that the rate of telomere loss is evolutionarily conserved within bird
      families. This suggests that the physiological causes of telomere shortening, or
      the ability to maintain telomeres, are features that may be responsible for, or
      co-evolved with, different lifespans observed across species.This article is part
      of the theme issue 'Understanding diversity in telomere dynamics'.

PMID- 29335370
TI  - Somatic growth and telomere dynamics in vertebrates: relationships, mechanisms
      and consequences.
AB  - Much telomere loss takes place during the period of most rapid growth when cell
      proliferation and potentially energy expenditure are high. Fast growth is linked
      to reduced longevity. Therefore, the effects of somatic cell proliferation on
      telomere loss and cell senescence might play a significant role in driving the
      growth-lifespan trade-off. While different species will have evolved a growth
      strategy that maximizes lifetime fitness, environmental conditions encountered
      during periods of growth will influence individual optima. In this review, we
      first discuss the routes by which altered cellular conditions could influence
      telomere loss in vertebrates, with a focus on oxidative stress in both in vitro
      and in vivo studies. We discuss the relationship between body growth and telomere
      length, and evaluate the empirical evidence that this relationship is generally
      negative. We further discuss the potentially conflicting hypotheses that arise
      when other factors are taken into account, and the further work that needs to be
      undertaken to disentangle confounding variables.This article is part of the theme
      issue 'Understanding diversity in telomere dynamics'.

PMID- 29335371
TI  - The relationship between telomere length and mortality risk in non-model
      vertebrate systems: a meta-analysis.
AB  - Telomere length (TL) has become a biomarker of increasing interest within ecology
      and evolutionary biology, and has been found to predict subsequent survival in
      some recent avian studies but not others. Here, we undertake the first formal
      meta-analysis to test whether there is an overall association between TL and
      subsequent mortality risk in vertebrates other than humans and model laboratory
      rodents. We identified 27 suitable studies and obtained standardized estimates of
      the hazard ratio associated with TL from each. We performed a meta-analysis on
      these estimates and found an overall significant negative association implying
      that short telomeres are associated with increased mortality risk, which was
      robust to evident publication bias. While we found that heterogeneity in the
      hazard ratios was not explained by sex, follow-up period, maximum lifespan or the
      age group of the study animals, the TL-mortality risk association was stronger in
      studies using qPCR compared to terminal restriction fragment methodologies. Our
      results provide support for a consistent association between short telomeres and
      increased mortality risk in birds, but also highlight the need for more research
      into non-avian vertebrates and the reasons why different telomere measurement
      methods may yield different results.This article is part of the theme issue
      'Understanding diversity in telomere dynamics'.

PMID- 29335373
TI  - Ectothermic telomeres: it's time they came in from the cold.
AB  - We review the evolutionary ecology and genetics of telomeres in taxa that cannot
      elevate their body temperature to a preferred level through metabolism but do so
      by basking or seeking out a warm environment. This group of organisms contains
      all living things on earth, apart from birds and mammals. One reason for our
      interest in this synthetic group is the argument that high, stable body
      temperature increases the risk of malignant tumours if long, telomerase-restored
      telomeres make cells 'live forever'. If this holds true, ectotherms should have
      significantly lower cancer frequencies. We discuss to what degree there is
      support for this 'anti-cancer' hypothesis in the current literature. Importantly,
      we suggest that ectothermic taxa, with variation in somatic telomerase expression
      across tissue and taxa, may hold the key to understanding ongoing selection and
      evolution of telomerase dynamics in the wild. We further review endotherm
      specific effects of growth on telomeres, effects of autotomy ('tail dropping') on
      telomere attrition, and costs of maintaining sexual displays measured in telomere
      attrition. Finally, we cover plant ectotherm telomeres and life histories in a
      separate 'mini review'.This article is part of the theme issue 'Understanding
      diversity in telomere dynamics'.

PMID- 29335372
TI  - All's well that ends well: why large species have short telomeres.
AB  - Among mammal species, almost all life-history traits are strongly size dependent.
      This size dependence even occurs at a molecular level. For example, both telomere
      length and telomerase expression show a size-dependent threshold. With some
      exceptions, species smaller than approximately 2 kg express telomerase, while
      species larger than that do not. Among species greater than approximately 5 kg,
      telomeres tend to be short-less than 25 kb-while among smaller species, some
      species have short and some have long telomeres. Here, we present a model to
      explore the role of body size-dependent trade-offs in shaping this threshold. We
      assume that selection favours short telomeres as a mechanism to protect against
      cancer. At the same time, selection favours long telomeres as a protective
      mechanism against DNA damage and replicative senescence. The relative importance
      of these two selective forces will depend on underlying intrinsic mortality and
      risk of cancer, both of which are size-dependent. Results from this model suggest
      that a cost-benefit model for the evolution of telomere length could explain
      phylogenetic patterns observed within the Class Mammalia. In addition, the model
      suggests a general conceptual framework to think about the role that body size
      plays in the evolution of tumour suppressor mechanisms.This article is part of
      the theme issue 'Understanding diversity in telomere dynamics'.

PMID- 29335374
TI  - Understanding diversity in telomere dynamics.

PMID- 29335375
TI  - Reflections on telomere dynamics and ageing-related diseases in humans.
AB  - Epidemiological studies have principally relied on measurements of telomere
      length (TL) in leucocytes, which reflects TL in other somatic cells. Leucocyte TL
      (LTL) displays vast variation across individuals-a phenomenon already observed in
      newborns. It is highly heritable, longer in females than males and in individuals
      of African ancestry than European ancestry. LTL is also longer in offspring
      conceived by older men. The traditional view regards LTL as a passive biomarker
      of human ageing. However, new evidence suggests that a dynamic interplay between
      selective evolutionary forces and TL might result in trade-offs for specific
      health outcomes. From a biological perspective, an active role of TL in ageing
      related human diseases could occur because short telomeres increase the risk of a
      category of diseases related to restricted cell proliferation and tissue
      degeneration, including cardiovascular disease, whereas long telomeres increase
      the risk of another category of diseases related to increased proliferative
      growth, including major cancers. To understand the role of telomere biology in
      ageing-related diseases, it is essential to expand telomere research to newborns
      and children and seek further insight into the underlying causes of the variation
      in TL due to ancestry and geographical location.This article is part of the theme
      issue 'Understanding diversity in telomere dynamics'.

PMID- 29335376
TI  - Telomeres and genomic evolution.
AB  - The terminal regions of eukaryotic chromosomes, composed of telomere repeat
      sequences and sub-telomeric sequences, represent some of the most variable and
      rapidly evolving regions of the genome. The sub-telomeric regions are
      characterized by segmentally duplicated repetitive DNA elements, interstitial
      telomere repeat sequences and families of variable genes. Sub-telomeric repeat
      sequence families are shared among multiple chromosome ends, often rendering
      detailed sequence characterization difficult. These regions are composed of
      constitutive heterochromatin and are subjected to high levels of meiotic
      recombination. Dysfunction within telomere repeat arrays, either due to
      disruption in the chromatin structure or because of telomere shortening, can lead
      to chromosomal fusion and the generation of large-scale genomic rearrangements
      across the genome. The dynamic nature of telomeric regions, therefore, provides
      functionally useful variation to create genetic diversity, but also provides a
      mechanism for rapid genomic evolution that can lead to reproductive isolation and
      speciation. This article is part of the theme issue 'Understanding diversity in
      telomere dynamics'.This article is part of the theme issue 'Understanding
      diversity in telomere dynamics'.

PMID- 29335377
TI  - Heritability of telomere variation: it is all about the environment!
AB  - Individual differences in telomere length have been linked to survival and
      senescence. Understanding the heritability of telomere length can provide
      important insight into individual differences and facilitate our understanding of
      the evolution of telomeres. However, to gain accurate and meaningful estimates of
      telomere heritability it is vital that the impact of the environment, and how
      this may vary, is understood and accounted for. The aim of this review is to
      raise awareness of this important, but much under-appreciated point. We outline
      the factors known to impact telomere length and discuss the fact that telomere
      length is a trait that changes with age. We highlight statistical methods that
      can separate genetic from environmental effects and control for confounding
      variables. We then review how well previous studies in vertebrate populations
      including humans have taken these factors into account. We argue that studies to
      date either use methodological techniques that confound environmental and genetic
      effects, or use appropriate methods but lack sufficient power to fully separate
      these components. We discuss potential solutions. We conclude that we need larger
      studies, which also span longer time periods, to account for changing
      environmental effects, if we are to determine meaningful estimates of the genetic
      component of telomere length.This article is part of the theme issue
      'Understanding diversity in telomere dynamics'.

PMID- 29335378
TI  - Comparison of telomere length measurement methods.
AB  - The strengths and limitations of the major methods developed to measure telomere
      lengths (TLs) in cells and tissues are presented in this review. These include Q
      PCR (Quantitative Polymerase Chain Reaction), TRF (Terminal Restriction Fragment)
      analysis, a variety of Q-FISH (Quantitative Fluorescence In Situ Hybridization)
      methods, STELA (Single TElomere Length Analysis) and TeSLA (Telomere Shortest
      Length Assay). For each method, we will cover information about validation
      studies, including reproducibility in independent laboratories, accuracy,
      reliability and sensitivity for measuring not only the average but also the
      shortest telomeres. There is substantial evidence that it is the shortest
      telomeres that trigger DNA damage responses leading to replicative senescence in
      mammals. However, the most commonly used TL measurement methods generally provide
      information on average or relative TL, but it is the shortest telomeres that
      leads to telomere dysfunction (identified by TIF, Telomere dysfunction Induced
      Foci) and limit cell proliferation in the absence of a telomere maintenance
      mechanism, such as telomerase. As the length of the shortest telomeres is a key
      biomarker determining cell fate and the onset of senescence, a new technique
      (TeSLA) that provides quantitative information about all the shortest telomeres
      will be highlighted.This article is part of the theme issue 'Understanding
      diversity in telomere dynamics'.

PMID- 29335379
TI  - The role of telomeres in the mechanisms and evolution of life-history trade-offs
      and ageing.
AB  - Evolutionary biology and biomedicine have seen a surge of recent interest in the
      possibility that telomeres play a role in life-history trade-offs and ageing.
      Here, I evaluate alternative hypotheses for the role of telomeres in the
      mechanisms and evolution of life-history trade-offs and ageing, and highlight
      outstanding challenges. First, while recent findings underscore the possibility
      of a proximate causal role for telomeres in current-future trade-offs and ageing,
      it is currently unclear (i) whether telomeres ever play a causal role in either
      and (ii) whether any causal role for telomeres arises via shortening or length
      independent mechanisms. Second, I consider why, if telomeres do play a proximate
      causal role, selection has not decoupled such a telomere-mediated trade-off
      between current and future performance. Evidence suggests that evolutionary
      constraints have not rendered such decoupling impossible. Instead, a causal role
      for telomeres would more plausibly reflect an adaptive strategy, born of telomere
      maintenance costs and/or a function for telomere attrition (e.g. in countering
      cancer), the relative importance of which is currently unclear. Finally, I
      consider the potential for telomere biology to clarify the constraints at play in
      life-history evolution, and to explain the form of the current-future trade-offs
      and ageing trajectories that we observe today.This article is part of the theme
      issue 'Understanding diversity in telomere dynamics'.

PMID- 29335380
TI  - Mitochondrial activity in gametes and uniparental inheritance: a comment on 'What
      can we infer about the origin of sex in early eukaryotes?'

PMID- 29335382
TI  - The mitochondrial genome, paternal age and telomere length in humans.
AB  - Telomere length (TL) in humans is highly heritable and undergoes progressive age
      dependent shortening in somatic cells. By contrast, sperm donated by older men
      display comparatively long telomeres, presumably because in the male germline,
      telomeres become longer with age. This puzzling phenomenon might explain why TL
      in the offspring correlates positively with paternal age. The present
      communication proposes that mitochondrial DNA polymorphisms and heteroplasmy
      cause variation in the production of reactive oxygen species, which, in turn,
      mediate age-dependent selection of germ stem cells with long telomeres and hence
      sperm with long telomeres. These long telomeres are then inherited by the
      offspring. The effect of paternal age on the offspring TL might be an
      evolutionarily driven mechanism that helps regulate TL across the human
      population.This article is part of the theme issue 'Understanding diversity in
      telomere dynamics'.

PMID- 29335383
TI  - Response to Ghiselli F et al. (2018).

PMID- 29335384
TI  - Predictors of Hemodynamic Improvement and Stabilization Following Intraaortic
      Balloon Pump Implantation in Patients With Advanced Heart Failure.
AB  - OBJECTIVES: The intraaortic balloon pump (IABP) is currently an essential tool to
      improve hemodynamics in patients with advanced heart failure (HF). This study
      investigated predictors for hemodynamic improvement or stabilization with IABP
      therapy in patients with advanced HF. METHODS: Patients with advanced HF and
      hemodynamic deterioration treated with IABP were enrolled in this retrospective
      study. Invasive hemodynamics were measured before IABP implantation and 2 weeks
      after IABP initiation. Significant degree of hemodynamic improvement was defined
      as 30% improvement in all three of the following variables: central venous
      pressure (CVP); pulmonary capillary wedge pressure (PCWP); and cardiac index
      (CI). Hemodynamic stabilization was counted in patients reaching CVP <12 mm Hg,
      PCWP <18 mm Hg, and CI >2.0 L/min/m2 or CI >2.2 L/min/m2 on inotropes. RESULTS:
      Ninety-one patients (55 +/- 12 years; 78% males) were evaluated. Seventeen
      patients (18.7%) achieved significant hemodynamic improvement, and baseline CVP
      >16 mm Hg was associated with this endpoint (P<.05). Thirty-two patients (35.2%)
      achieved hemodynamic stabilization; lower baseline heart rate (HR) and PCWP were
      associated with this stabilization (P<.05). Patients with HR <92 beats/min and
      PCWP <25 mm Hg achieved hemodynamic stabilization more frequently than those
      without HR <92 beats/min and PCWP <25 mm Hg (66.7% vs 19.7%; P<.05). CONCLUSION:
      Elevated CVP and lower HR and PCWP before IABP initiation help predict high
      response to IABP.

PMID- 29335386
TI  - Safety and Feasibility of a Novel, Second-Generation Robotic-Assisted System for
      Percutaneous Coronary Intervention: First-in-Human Report.
AB  - OBJECTIVES: The goal of this study is to evaluate the safety and efficacy of the
      second-generation robotic-assisted system CorPath GRX (Corindus) for percutaneous
      coronary intervention (PCI). BACKGROUND: The first-generation CorPath 200 robotic
      assisted system for PCI is effective, but is limited by the lack of an active
      robotic guide-catheter control. The CorPath GRX device enables robotic guide
      catheter manipulation, in addition to guidewire and balloon/stent delivery.
      However, there have been no clinical data reported with this device. METHODS:
      Consecutive patients with demonstrated obstructive coronary artery disease (>70%
      stenosis) and clinical indications for PCI were treated with the CorPath GRX
      system and enrolled in the study. The two co-primary endpoints were clinical
      procedural success (final TIMI 3 flow, and <30% residual stenosis without in
      hospital major adverse cardiac event) and device technical success (robotic
      clinical procedural success without the need for unplanned manual
      assistance/conversion). RESULTS: The study enrolled 40 subjects (65.7 +/- 11.9
      years; 72.5% males; 54 lesions) with a high proportion of American College of
      Cardiology/American Heart Association type B2/C lesions (77.8%). Clinical
      procedural success and device technical success rates were 97.5% (n = 39 of 40)
      and 90.0% (n = 36 of 40), respectively. CONCLUSION: The second-generation CorPath
      GRX system for robotic-assisted PCI is safe and effective, and achieves high
      rates of clinical and technical success in a cohort of patients with complex
      coronary disease.

PMID- 29335385
TI  - A Transradial Approach of Cardiac Catheterization for Patients on Dialysis.
AB  - BACKGROUND: Periprocedural bleeding is associated with increased risk of early
      mortality during percutaneous coronary intervention (PCI), especially in patients
      on dialysis. A transradial approach (TRA) should be considered for these
      patients; however, PCI operators avoid this approach because of the risk of
      radial artery occlusion (RAO). The aim of this study is to construct a TRA system
      and clarify its safety in patients on dialysis. METHODS: Eighty-eight consecutive
      patients on dialysis who underwent cardiac catheterization were prospectively
      included in this study and divided according to the access site into either the
      TRA group or the transfemoral approach (TFA) group. Radial access was limited in
      the opposite side of arteriovenous fistula. The study endpoints were in-hospital
      and 30-day mortality rates, puncture-site related bleeding complications, and
      other complications. The study safety endpoints were procedure success rate and
      RAO rate in the TRA group. RESULTS: Mean patient age was 70.4 +/- 8.5 years. PCI
      was performed in 43 patients (48.9%). The TRA and TFA groups included 62 patients
      (70.5%) and 26 patients (29.5%), respectively. In-hospital and 30-day mortality
      rates were 0.0% in both groups. Puncture-site bleeding rates were 3.8% in the TFA
      group and 0.0% in the TRA group (P=.12). Procedural success rate in the TRA group
      was 98.4%. Crossover to TFA was necessary in 1 patient due to radial artery
      spasm. RAO occurred in 4 patients (6.5%). CONCLUSIONS: Constructed TRA can be
      safely used in patients on dialysis. Our study could lead to an increase in TRA
      in these patients, which would lead to better prognosis and patient comfort.

PMID- 29335387
TI  - Clear Cell Carcinoma of the abdominal wall.
AB  - BACKGROUND: Clear cell carcinoma in scars after cesarean section is extremely
      rare, with only 22 cases reported in the literature. Management of this condition
      needs to be further explored. Here, we report of a patient with clear cell
      carcinoma of the abdominal wall that developed 35 years after cesarean section.
      CASE REPORT: The material of the study was a group of 61 patients divided into
      two groups. Group I - 35 deaf or with profound sensorineural hearing loss
      children (the pupils of the deaf and hard of hearing school), aged 5-17 years
      (average 9,2 years), 14 males, 21 females, II - control group comprised 26 normal
      hearing patients, aged 5-16 years (average 10,4 years), 14 males, 12 females
      (patients of Department of Pediatric Otolaryngology, Audiology and Phoniatrics,
      Medical University of Lodz). In both groups, exon 2 sequencing of GJB2 gene was
      performed. RESULTS: A 58-year-old woman was admitted to our department due to
      abdominal pain and a progressively growing mass in the abdominal wall. Based on
      biopsy, a preliminary diagnosis of clear cell carcinoma was made. A wide surgical
      excision of the tumor with clear margins, hysterectomy with bilateral salpingo
      oophorectomy, and abdominal wall reconstruction using synthetic mesh were
      performed. The patient was discharged in good condition after fifteen days of
      hospitalization. The patient remained recurrence-free 6 months after the
      treatment. CONCLUSIONS: T Lack of standardized management of rare malignant
      transformations hinders patient care. Due to a growing number of cesarean
      deliveries, we can expect clear cell carcinoma prevalence of the abdominal wall
      to increase. Therefore, patients and clinicians should attend to any pain,
      itching, or change in the size of abdominal wall scars.

PMID- 29335381
TI  - The fetal programming of telomere biology hypothesis: an update.
AB  - Research on mechanisms underlying fetal programming of health and disease risk
      has focused primarily on processes that are specific to cell types, organs or
      phenotypes of interest. However, the observation that developmental conditions
      concomitantly influence a diverse set of phenotypes, the majority of which are
      implicated in age-related disorders, raises the possibility that such
      developmental conditions may additionally exert effects via a common underlying
      mechanism that involves cellular/molecular ageing-related processes. In this
      context, we submit that telomere biology represents a process of particular
      interest in humans because, firstly, this system represents among the most
      salient antecedent cellular phenotypes for common age-related disorders;
      secondly, its initial (newborn) setting appears to be particularly important for
      its long-term effects; and thirdly, its initial setting appears to be plastic and
      under developmental regulation. We propose that the effects of suboptimal
      intrauterine conditions on the initial setting of telomere length and telomerase
      expression/activity capacity may be mediated by the programming actions of stress
      related maternal-placental-fetal oxidative, immune, endocrine and metabolic
      pathways in a manner that may ultimately accelerate cellular dysfunction, ageing
      and disease susceptibility over the lifespan. This perspectives paper provides an
      overview of each of the elements underlying this hypothesis, with an emphasis on
      recent developments, findings and future directions.This article is part of the
      theme issue 'Understanding diversity in telomere dynamics'.

PMID- 29335388
TI  - Association between clinical stage of oral cancer and expression of
      immunohistochemical markers.
AB  - AIM: The aim of this study is to demonstrate the possible correlation between the
      expression of examined protein markers - p53, EGFR, PCNA, p44/42 in the mass of
      the tumor and the clinical stage of disease. MATERIAL: 48 patients of the
      Department and Clinic of Oral and Maxillofacial Surgery, Lublin diagnosed with
      oral cancer. The control group consisted of 10 patients diagnosed with
      leukoplakia lesions in the oral cavity. The methods: Immunohistochemical analysis
      using the detection system DAKO K5007 Cat - Dako REAL TM Detection System,
      Peroxidase DAB +, Rabbit / Mouse. RESULTS: Based upon the statistical results,
      significant correlation between p53 protein and tumor staging; however, a
      correlation between the level of expression of EGFR, p44/42, PCNA and staging was
      not likewise revealed. CONCLUSIONS: Looking for oral squamous cell carcinoma
      markers remains an actual issue. Identification of specific markers of oral
      cancer could be used in screening the population, determining prognosis and
      response to treatment.

PMID- 29335389
TI  - Checklist in colorectal surgery - proposal of experts of the Polish Club of
      Coloproctology and National Consultant in general surgery.
AB  - A checklist is a collection of information that helps reduce the risk of failure
      due to limitations in human memory and attention. In surgery, the first Surgical
      Safety Checklist (SSC), created under the supervision of WHO (World Health
      Organization), was established in 2007 and covers three stages related to the
      patient's stay in the operating theater and operation: 1. Prior to initiation
      (induction) of anesthesia; 2. before cutting the skin; 3. before the patient
      leaves the operating room Colorectal surgery is particularly at high risk for
      complications and relatively high mortality. Elimination or, more likely,
      reducing the risk of complications by standardizing perioperative procedures may
      be particularly important in this group. The introduction of "dedicated"
      colorectal checklist surgery seems to be justified. The checklist proposed by the
      authors in colorectal surgery is divided into four stages, in which conscientious
      completion of checklists is intended to reduce the potential risk of
      complications due to hospitalization and surgical treatment. The presented
      checklist is obviously not closed, as a new publications or recommendations
      appear, some points may be modified, new issues may be added to the checklist. At
      present, however, it is a tool considering the well-known and confirmed elements
      of intraoperative procedures, the compliance of which may significantly reduce
      the rate of adverse events or surgical complications.

PMID- 29335390
TI  - Direct Trocar Insertion with Elevation of the Rectus Sheath in Bariatric Surgery:
      A Novel Technique.
AB  - INTRODUCTION: Initial trocar entry, the first step in laparoscopic surgery, is
      associated with several complications. In morbidly obese patients, initial trocar
      placement is associated with a greater number of complications compared to non
      obese patients. Materials and Surgical Technique. In this study, we describe our
      use of an initial trocar entry technique which is direct trocar insertion with
      elevation of the rectus sheath by a single Backhaus towel clamp and we would like
      to evaluate the sa fety and efficacy of its administration in bariatric surgery.
      DISCUSSION: Our results indicate that gaining initial trocar entry using our
      technique leads to successful laparoscopic bariatric surgery. Our technique is a
      safe, effective, and reliable first step in successful laparoscopic surgery for
      almost all patients, and is only contraindicated in patients with severe
      hepatomegaly.

PMID- 29335391
TI  - Renal vascularization anomalies in the Polish population.
AB  - : The aim of the study was to determine the incidence of renal venous system
      congenital anomalies in the Polish population. MATERIAL AND METHOD: Vascular
      kidney samples were investigated by means of preparations and X-ray contrasting.
      The study the group comprised 281 male and 269 female specimens. RESULTS:
      Congenital anomalies were diagnosed in 186 patients (33 8% of all cases), and
      they were more frequent in men than in women, albeit that difference was non
      significant. The following anomalies were most commonly observed: multiple venous
      variations on the right side (20.4%), retroaortic course of the left renal vein
      (4.2%), and circumaortic venous ring of the left renal vein (3.8%). Other
      anomalies were diagnosed in 1%-2% of cases. CONCLUSIONS: Awareness and
      preoperative assessment of the venous system before abdominal aortic surgery,
      isolated collection of renal venous blood samples, and urological or kidney
      transplantation procedures is essential.

PMID- 29335392
TI  - Cytoreductive surgery and HIPEC in the treatment of peritoneal metastases of
      sarcomas and other rare malignancies.
AB  - .................................... Cytoreductive surgery and HIPEC in the
      treatment of peritoneal metastases of sarcomas and other rare malignancies.

PMID- 29335393
TI  - Peritoneal metastases of colorectal origin - cytoreductive surgery and
      hyperthermic intraperitoneal chemotherapy (HIPEC). The financial aspect.
AB  - The incidence of peritoneal carcinomatosis of colorectal cancer amounts to 5%-15%
      for synchronous metastases and as much as 40% in cases of local recurrence. Best
      results are obtained for cytoreductive surgery combined with hyperthermic
      intraperitoneal chemotherapy (HIPEC). This treatment offers much better outcomes,
      leading to 5-year survival rates of as much as 30%-50%. The procedures require
      significant experience in abdominal surgery, are time-consuming (mean duration of
      the procedure ranging from 6 to 8 hours) and are burdened by complications that
      are due not only to the procedure itself but also to the intraperitoneal
      administration of the cytostatic drug at elevated temperature (41.5  degrees C).
      After the procedure, patients are required to be admitted to intensive care units
      due to potential complications associated with the extent and duration of the
      procedure as well as chemotherapy administered in hyperthermia. Postoperative
      management of these patients requires appropriate experience of the entire
      medical and nursing team. Cytoreductive surgeries combined with HIPEC as highly
      specialized medical procedures should be assessed for their potential long-term
      benefits and their costs should be appropriately calculated with consideration to
      realistic reimbursement rates. Realistic valuation and reimbursement covering the
      overall average cost of the procedure is recommended by the National Consultant
      in Surgical Oncology as well as the ESMO consensus guidelines.

PMID- 29335394
TI  - Landscape of oncoplastic breast surgery across Poland.
AB  - Oncoplastic and reconstructive techniques are essential tools in the
      armamentarium of contemporary breast surgeons. The aim of the study was to
      identify oncoplastic reconstructive patterns in breast cancer centers across
      Poland. A questionnaire of 18 questions was sent by email to the members of the
      Polish Society of Surgical Oncology and the Polish Society of Plastic,
      Reconstructive and Esthetic Surgery via their dedicated websites. The numbers of
      breast cancer patients operated on in each center ranged from 120 to 904 per
      year. Breast-conserving surgery (BCS) predominated in all but one center (range
      50-70%). Immediate breast reconstructions (IBR) accounted for 6-42% of
      procedures, The most frequent type of IBR was either a two-stage expander
      followed by a permanent implant or one-stage implant- based with or without
      synthetic mesh. The most frequent type of delayed breast reconstruction (DBR) was
      a two-stage expander followed by implant-based reconstruction. None of the
      surveyed cancer centers performed free flap reconstruction. Deep inferior
      epigastric perforator (DIEP) flaps were performed in the plastic surgery
      department. Reconstructions based on pedicled flaps were performed in cancer
      centers. Acellular dermal matrices (ADM) and fat transfer were used in selected
      centers. In the clinical scenario of adjuvant radiotherapy, delayed breast
      reconstruction was favored. The full range of oncoplastic BCS was performed.
      Patient-reported outcome measures (PROM) and complications were assessed. Our
      findings can act as a platform for further improvement in skills, certification,
      data collection and audit, including patient reported expectation measures. There
      is also an urgent need to address pan-European inconsistencies in procedural
      reimbursement.

PMID- 29335395
TI  - Predictors of recanalization after endovascular treatment of posterior
      circulation aneurysms.
AB  - INTRODUCTION: Posterior circulation aneurysms account for approximately 30% of
      all intracranial aneurysms, and their rupture often causes aneurysmal
      subarachnoid hemorrhage (aSAH). Because surgical treatment of posterior
      circulation aneurysms is difficult, endovascular treatment is commonly indicated.
      However, simple coil embolization is associated with a high rate of
      recanalization. Our goal was to investigate morphometric aneurysmal features
      assessed on pre-embolization computed tomography angiography (CTA) as predictors
      of recanalization in patients with posterior circulation aneurysms. MATERIAL AND
      METHODS: We retrospectively analyzed data of 24 patients who underwent coil
      embolization due to rupture of saccular posterior circulation aneurysms. The
      morphometric features of aneurysms were measured based on pre-embolization 3D-CTA
      aneurysm models, and aneurysmal size and volume were measured on digital
      subtraction angiography (DSA) images. The effectiveness of initial endovascular
      treatment was determined visually with the modified Raymond Roy classification
      directly after embolization and on follow-up DSAs. Recanalization was diagnosed
      when, compared to the primary embolization aneurysm appearance, compaction and
      filling of the aneurysm occurred. Statistical analysis was performed with
      Statistica 13.1 software. RESULTS: Higher maximal aneurysm height perpendicular
      to the aneurysmal neck was associated with a greater aneurysm recanalization risk
      (12.12+/-5.13mm vs. 7.41+/-3.97mm, p=0.039), and this relationship remained
      significant after adjustment for patient's age, sex and aneurysm localization
      (OR=1.26, 95%CI: 1.01-1.60, p=0.047). Maximal aneurysm height perpendicular to
      the aneurysmal neck distinguished well between recanalized and non-recanalized
      aneurysms (AUC=0.755, 95%CI: 0.521- 0.989, p=0.033). CONCLUSIONS: Predictors of
      aneurysm recanalization can help choose best endovascular treatment strategies,
      which could reduce complication rates.

PMID- 29335396
TI  - Barogenic rupture of esophagus (Boerhaave syndrome) as diagnostic and therapeutic
      challenge requiring rapid and effective interdisciplinary cooperation - case
      report.
AB  - We describe a 47-year-old male who was admitted to our centre from a local
      emergency unit with septic shock due to suspected Boerhaave syndrome. After the
      diagnosis was confirmed, the patient underwent emergency surgery.
      Postoperatively, the patient had symptoms of acute alcoholic delirium, and
      developed an oesophagomediastinal fistula as the most serious local complication.
      Successful conservative treatment enabled complete healing of the fistula,
      leading to patient recovery. No late complications like oesophageal stenosis were
      found at 6 months from discharge.

PMID- 29335397
TI  - Pediatric Renal Transplantation: Focus on Current Transition Care and Proposal of
      the "RISE to Transition" Protocol.
AB  - The transition from pediatric to adult medical services is an important time in
      the life of an adolescent or young adult with a renal transplant. Failure of
      proper transition can lead to medical non-adherence and subsequent loss of graft
      and/or return to dialysis. The aim of this study was to conduct a systematic
      review and survey to assess the challenges and existing practices in transition
      of renal transplant recipient children to adult services, and to develop a
      transition protocol. We conducted a literature review and performed a survey of
      pediatric nephrologists across the United States to examine the current state of
      transition care. A structured transition protocol was developed based on these
      results. Our literature review revealed that a transition program has a positive
      impact on decline in renal function and acute rejection episodes, and may improve
      long-term graft outcomes in pediatric kidney transplant patients. With a response
      rate of 40% (60/150) from nephrologists in 56% (49/87) of centers, our survey
      shows inconsistent use of validated tools despite their availability, inefficient
      communication between teams, and lack of use of dedicated clinics. To address
      these issues, we developed the "RISE to Transition" protocol, which relies on 4
      competency areas: Recognition, Insight, Self-reliance, and Establishment of
      healthy habits. The transition program decreases acute graft rejection episodes,
      and the main challenges in transition care are the communication gap between
      health care providers and inconsistent use of transition tools. Our RISE to
      transition protocol incorporates transition tools, defines personnel, and aims to
      improve communication between teams.

PMID- 29335398
TI  - Massive Post-Obstructive Diuresis.
AB  - BACKGROUND The purpose of presenting this case is to demonstrate the degree to
      which the kidney is capable of selectively excreting a massive load of sodium and
      water when challenged with both of these, without altering the plasma levels of
      other ions. CASE REPORT An 8-year-old boy was admitted in severe renal failure.
      Workup demonstrated a high grade obstruction of a single kidney. Following
      dialysis, the patient underwent surgery to correct the obstruction and he
      developed post-obstructive diuresis. Within one week he was receiving 34 liters
      of essentially 1/2 Na by IV and by mouth and was excreting 70% of his filtered
      load of water and 50% of his filtered load of sodium. As soon as the administered
      fluids and Na were cut back, the kidney responded appropriately. CONCLUSIONS
      While post-obstructive diuresis is a real phenomenon, very frequently it is
      magnified by forcing diuresis with the administration of too much water. These
      patients are best treated by administering fluids to equal output for two to
      three days and then gradually cutting back on fluid intake. If the kidney
      responds appropriately, then fluids can be given as the patient requests.

PMID- 29335399
TI  - Prevalence and Causes of Visual Impairment in Adults in Binhu District, Wuxi,
      China.
AB  - BACKGROUND Previously reported data has guided the treatment and prevention of
      blindness. This study aimed to evaluate the current prevalence and causes of
      visual impairment among adults who were 50 years old and older in the Binhu
      District of Wuxi City, China. MATERIAL AND METHODS A randomized sample of
      stratified clusters was used to analyze individuals from 30 basic sampling units
      in Wuxi Binhu District. Visual impairment was defined according to World Health
      Organization (WHO) standards. RESULTS A total of 6725 people who were at least 50
      years old participated in this study. According to WHO standards, bilateral low
      vision and blindness prevalence were both higher in women than in men (low
      vision: 6.5% vs. 5.2%; and blindness: 1.4% vs. 0.8%; P=0.022 and P=0.039,
      respectively). The incidence of bilateral visual impairment increased
      significantly with age (P<0.001 and P<0.001, respectively). Further studies
      showed that the main causes of bilateral low vision were cataract, high myopic
      macular degeneration (MMD), and age-related macular degeneration (AMD). The main
      causes of bilateral blindness were cataract, MMD, and eye loss/atrophy, while the
      main causes of monocular low vision were cataract, MD, and AMD. The main causes
      of monocular blindness were cataract, eye loss/atrophy, and AMD. CONCLUSIONS The
      prevalence of low vision and blindness remains high in the Binhu District of Wuxi
      City in China, especially among older women. In our study, cataracts were the
      leading cause of visual impairment. Our study highlights that some efforts should
      be initiated to prevent and treat blindness and low vision. Additional causes of
      visual impairment were MMD, AMD, and eye loss/atrophy.

PMID- 29335401
TI  - Author Correction: Spiraling pathways of global deep waters to the surface of the
      Southern Ocean.
AB  - The original version of this Article contained errors in Fig. 6. In panel a, the
      grey highlights obscured the curves for CESM, CM2.6 and SOSE, and the labels
      indicating SWIR, KP, MR, PAR, and DP were inadvertently omitted. These have now
      been corrected in both the PDF and HTML versions of the Article.

PMID- 29335400
TI  - Causal associations between risk factors and common diseases inferred from GWAS
      summary data.
AB  - Health risk factors such as body mass index (BMI) and serum cholesterol are
      associated with many common diseases. It often remains unclear whether the risk
      factors are cause or consequence of disease, or whether the associations are the
      result of confounding. We develop and apply a method (called GSMR) that performs
      a multi-SNP Mendelian randomization analysis using summary-level data from genome
      wide association studies to test the causal associations of BMI, waist-to-hip
      ratio, serum cholesterols, blood pressures, height, and years of schooling
      (EduYears) with common diseases (sample sizes of up to 405,072). We identify a
      number of causal associations including a protective effect of LDL-cholesterol
      against type-2 diabetes (T2D) that might explain the side effects of statins on
      T2D, a protective effect of EduYears against Alzheimer's disease, and
      bidirectional associations with opposite effects (e.g., higher BMI increases the
      risk of T2D but the effect of T2D on BMI is negative).

PMID- 29335402
TI  - A partially-open inward-facing intermediate conformation of LeuT is associated
      with Na+ release and substrate transport.
AB  - Neurotransmitter:sodium symporters (NSS), targets of antidepressants and
      psychostimulants, clear neurotransmitters from the synaptic cleft through sodium
      (Na+)-coupled transport. Substrate and Na+ are thought to be transported from the
      extracellular to intracellular space through an alternating access mechanism by
      coordinated conformational rearrangements in the symporter that alternately
      expose the binding sites to each side of the membrane. However, the mechanism by
      which the binding of ligands coordinates conformational changes occurring on
      opposite sides of the membrane is not well understood. Here, we report the use of
      single-molecule fluorescence resonance energy transfer (smFRET) techniques to
      image transitions between distinct conformational states on both the
      extracellular and intracellular sides of the prokaryotic NSS LeuT, including
      partially open intermediates associated with transport activity. The nature and
      functional context of these hitherto unidentified intermediate states shed new
      light on the allosteric mechanism that couples substrate and Na+ symport by the
      NSS family through conformational dynamics.

PMID- 29335403
TI  - Floats with bio-optical sensors reveal what processes trigger the North Atlantic
      bloom.
AB  - The North Atlantic bloom corresponds to a strong seasonal increase in
      phytoplankton that produces organic carbon through photosynthesis. It is still
      debated what physical and biological conditions trigger the bloom, because
      comprehensive time series of the vertical distribution of phytoplankton biomass
      are lacking. Vertical profiles from nine floats that sampled the waters of the
      North Atlantic every few days for a couple of years reveal that phytoplankton
      populations start growing in early winter at very weak rates. A proper bloom with
      rapidly accelerating population growth rates instead starts only in spring when
      atmospheric cooling subsides and the mixed layer rapidly shoals. While the weak
      accumulation of phytoplankton in winter is crucial to maintaining a viable
      population, the spring bloom dominates the overall seasonal production of organic
      carbon.

PMID- 29335404
TI  - Publisher Correction: Second-order spectral lineshapes from charged interfaces.
AB  - The original version of this Article contained an error in Equation 3b. A ' + '
      sign incorrectly appeared instead of a '-' sign in the denominator of the right
      hand side of the equation and incorrectly read:[Formula: see text]The correct
      form of the equation is as follows:[Formula: see text]This has now been corrected
      in both the PDF and HTML versions of the Article.

PMID- 29335405
TI  - Author Correction: Myoblasts and macrophages are required for therapeutic
      morpholino antisense oligonucleotide delivery to dystrophic muscle.
AB  - In the original version of this Article, financial support was not fully
      acknowledged. The PDF and HTML versions of the Article have now been corrected to
      include support from the CRI Light Microscopy and Image Analysis Core.

PMID- 29335406
TI  - Thalidomide plus prednisone with or without danazol therapy in myelofibrosis: a
      retrospective analysis of incidence and durability of anemia response.
AB  - Low-dose thalidomide and prednisone alone or combined are effective therapies in
      some persons with primary myelofibrosis (PMF) and anemia with or with RBC
      transfusion dependence. Danazol is also effective in some persons with PMF and
      anemia. Responses to these drugs are typically incomplete and not sustained. It
      is unclear whether adding danazol to thalidomide and prednisone would improve
      efficacy. We retrospectively compared the outcomes of 88 subjects with PMF and
      anemia receiving thalidomide and prednisone without (n = 46) or with danazol (n =
      42). The primary end point was anemia response, which was 71% (95% confidence
      interval (CI), 57, 85%) in subjects receiving thalidomide/prednisone/danazol
      compared with 46% (32, 60%; P = 0.014) in those receiving thalidomide/prednisone.
      Response rates in subjects who were RBC transfusion dependent was also higher in
      the danazol cohort (61% (38, 84%)) vs. 25% (6, 44%); P = 0.024). Time to response
      was rapid (median, 2 months (range, 1-11 months)) and similar between the
      cohorts. Response duration was longer in the thalidomide/prednisone/danazol
      cohort (HR 2.18 (1.18-5.42); P = 0.019). Adverse effects were mild and similar
      between the cohorts. In conclusion, thalidomide/prednisone/danazol seems superior
      to thalidomide/prednisone in persons with PMF and anemia. Our conclusion requires
      confirmation in a randomized trial.

PMID- 29335407
TI  - Radical asymmetric intramolecular alpha-cyclopropanation of aldehydes towards
      bicyclo[3.1.0]hexanes containing vicinal all-carbon quaternary stereocenters.
AB  - The development of a general catalytic method for the direct and stereoselective
      construction of cyclopropanes bearing highly congested vicinal all-carbon
      quaternary stereocenters remains a formidable challenge in chemical synthesis.
      Here, we report an intramolecular radical cyclopropanation of unactivated alkenes
      with simple alpha-methylene group of aldehydes as C1 source via a Cu(I)/secondary
      amine cooperative catalyst, which enables the single-step construction of
      bicyclo[3.1.0]hexane skeletons with excellent efficiency, broad substrate scope
      covering various terminal, internal alkenes as well as diverse (hetero)aromatic,
      alkenyl, alkyl-substituted geminal alkenes. Moreover, this reaction has been
      successfully realized to an asymmetric transformation, providing an attractive
      approach for the construction of enantioenriched bicyclo[3.1.0]hexanes bearing
      two crucial vicinal all-carbon quaternary stereocenters with good to excellent
      enantioselectivity. The utility of this method is illustrated by facile
      transformations of the products into various useful chiral synthetic
      intermediates. Preliminary mechanistic studies support a stepwise radical process
      for this formal [2 + 1] cycloaddition.

PMID- 29335408
TI  - Escape from thymic deletion and anti-leukemic effects of T cells specific for
      hematopoietic cell-restricted antigen.
AB  - Whether hematopoietic cell-restricted distribution of antigens affects the degree
      of thymic negative selection has not been investigated in detail. Here, we show
      that T cells specific for hematopoietic cell-restricted antigens (HRA) are not
      completely deleted in the thymus, using the mouse minor histocompatibility
      antigen H60, the expression of which is restricted to hematopoietic cells. As a
      result, low avidity T cells escape from thymic deletion. This incomplete thymic
      deletion occurs to the T cells developing de novo in the thymus of H60-positive
      recipients in H60-mismatched bone marrow transplantation (BMT). H60-specific
      thymic deletion escapee CD8+ T cells exhibit effector differentiation potentials
      in the periphery and contribute to graft-versus-leukemia effects in the
      recipients of H60-mismatched BMT, regressing H60+ hematological tumors. These
      results provide information essential for understanding thymic negative selection
      and developing a strategy to treat hematological tumors.

PMID- 29335409
TI  - Electric-field control of anomalous and topological Hall effects in oxide bilayer
      thin films.
AB  - One of the key goals in spintronics is to tame the spin-orbit coupling (SOC) that
      links spin and motion of electrons, giving rise to intriguing magneto-transport
      properties in itinerant magnets. Prominent examples of such SOC-based phenomena
      are the anomalous and topological Hall effects. However, controlling them with
      electric fields has remained unachieved since an electric field tends to be
      screened in itinerant magnets. Here we demonstrate that both anomalous and
      topological Hall effects can be modulated by electric fields in oxide
      heterostructures consisting of ferromagnetic SrRuO3 and nonmagnetic SrIrO3. We
      observe a clear electric field effect only when SrIrO3 is inserted between SrRuO3
      and a gate dielectric. Our results establish that strong SOC of nonmagnetic
      materials such as SrIrO3 is essential in electrical tuning of these Hall effects
      and possibly other SOC-related phenomena.

PMID- 29335410
TI  - Abnormal phase transition between two-dimensional high-density liquid crystal and
      low-density crystalline solid phases.
AB  - Some two-dimensional liquid systems are theoretically predicted to have an
      anomalous phase transition due to unique intermolecular interactions, for example
      the first-order transition between two-dimensional high-density water and low
      density amorphous ice. However, it has never been experimentally observed, to the
      best of our knowledge. Here we report an entropy-driven phase transition between
      a high-density liquid crystal and low-density crystalline solid, directly
      observed by scanning tunneling microscope in carbon monoxide adsorbed on Cu(111).
      Combined with first principle calculations, we find that repulsive dipole-dipole
      interactions between carbon monoxide molecules lead to unconventional
      thermodynamics. This finding of unconventional thermodynamics in two-dimensional
      carbon monoxide not only provides a platform to study the fundamental principles
      of anomalous phase transitions in two-dimensional liquids at the atomic scale,
      but may also help to design and develop more efficient copper-based catalysis.

PMID- 29335411
TI  - Reconfiguring crystal and electronic structures of MoS2 by substitutional doping.
AB  - Doping of traditional semiconductors has enabled technological applications in
      modern electronics by tailoring their chemical, optical and electronic
      properties. However, substitutional doping in two-dimensional semiconductors is
      at a comparatively early stage, and the resultant effects are less explored. In
      this work, we report unusual effects of degenerate doping with Nb on structural,
      electronic and optical characteristics of MoS2 crystals. The doping readily
      induces a structural transformation from naturally occurring 2H stacking to 3R
      stacking. Electronically, a strong interaction of the Nb impurity states with the
      host valence bands drastically and nonlinearly modifies the electronic band
      structure with the valence band maximum of multilayer MoS2 at the Gamma point
      pushed upward by hybridization with the Nb states. When thinned down to
      monolayers, in stark contrast, such significant nonlinear effect vanishes,
      instead resulting in strong and broadband photoluminescence via the formation of
      exciton complexes tightly bound to neutral acceptors.

PMID- 29335412
TI  - Phosphorylation-induced conformation of beta2-adrenoceptor related to arrestin
      recruitment revealed by NMR.
AB  - The C-terminal region of G-protein-coupled receptors (GPCRs), stimulated by
      agonist binding, is phosphorylated by GPCR kinases, and the phosphorylated GPCRs
      bind to arrestin, leading to the cellular responses. To understand the mechanism
      underlying the formation of the phosphorylated GPCR-arrestin complex, we
      performed NMR analyses of the phosphorylated beta2-adrenoceptor (beta2AR) and the
      phosphorylated beta2AR-beta-arrestin 1 complex, in the lipid bilayers of
      nanodisc. Here we show that the phosphorylated C-terminal region adheres to
      either the intracellular side of the transmembrane region or lipids, and that the
      phosphorylation of the C-terminal region allosterically alters the conformation
      around M2155.54 and M2796.41, located on transemembrane helices 5 and 6,
      respectively. In addition, we found that the conformation induced by the
      phosphorylation is similar to that corresponding to the beta-arrestin-bound
      state. The phosphorylation-induced structures revealed in this study propose a
      conserved structural motif of GPCRs that enables beta-arrestin to recognize
      dozens of GPCRs.

PMID- 29335413
TI  - Heliconical smectic phases formed by achiral molecules.
AB  - Chiral symmetry breaking in soft matter is a hot topic of current research.
      Recently, such a phenomenon was found in a fluidic phase showing orientational
      order of molecules-the nematic phase; although built of achiral molecules, the
      phase can exhibit structural chirality-average molecular direction follows a
      short-pitch helix. Here, we report a series of achiral asymmetric dimers with an
      odd number of atoms in the spacer, which form twisted structures in nematic as
      well as in lamellar phases. The tight pitch heliconical nematic (NTB) phase and
      heliconical tilted smectic C (SmCTB) phase are formed. The formation of a variety
      of helical structures is accompanied by a gradual freezing of molecular rotation.
      In the lowest temperature smectic phase, HexI, the twist is expressed through the
      formation of hierarchical structure: nanoscale helices and mesoscopic helical
      filaments. The short-pitch helical structure in the smectic phases is confirmed
      by resonant X-ray measurements.

PMID- 29335414
TI  - Evolutionary history of Coleoptera revealed by extensive sampling of genes and
      species.
AB  - Beetles (Coleoptera) are the most diverse and species-rich group of insects, and
      a robust, time-calibrated phylogeny is fundamental to understanding
      macroevolutionary processes that underlie their diversity. Here we infer the
      phylogeny and divergence times of all major lineages of Coleoptera by analyzing
      95 protein-coding genes in 373 beetle species, including ~67% of the currently
      recognized families. The subordinal relationships are strongly supported as
      Polyphaga (Adephaga (Archostemata, Myxophaga)). The series and superfamilies of
      Polyphaga are mostly monophyletic. The species-poor Nosodendridae is robustly
      recovered in a novel position sister to Staphyliniformia, Bostrichiformia, and
      Cucujiformia. Our divergence time analyses suggest that the crown group of extant
      beetles occurred ~297 million years ago (Mya) and that ~64% of families
      originated in the Cretaceous. Most of the herbivorous families experienced a
      significant increase in diversification rate during the Cretaceous, thus
      suggesting that the rise of angiosperms in the Cretaceous may have been an
      'evolutionary impetus' driving the hyperdiversity of herbivorous beetles.

PMID- 29335415
TI  - USP48 restrains resection by site-specific cleavage of the BRCA1 ubiquitin mark
      from H2A.
AB  - BRCA1-BARD1-catalyzed ubiquitination of histone H2A is an important regulator of
      the DNA damage response, priming chromatin for repair by homologous
      recombination. However, no specific deubiquitinating enzymes (DUBs) are known to
      antagonize this function. Here we identify ubiquitin specific protease-48 (USP48)
      as a H2A DUB, specific for the C-terminal BRCA1 ubiquitination site. Detailed
      biochemical analysis shows that an auxiliary ubiquitin, an additional ubiquitin
      that itself does not get cleaved, modulates USP48 activity, which has possible
      implications for its regulation in vivo. In cells we reveal that USP48
      antagonizes BRCA1 E3 ligase function and in BRCA1-proficient cells loss of USP48
      results in positioning 53BP1 further from the break site and in extended
      resection lengths. USP48 repression confers a survival benefit to cells treated
      with camptothecin and its activity acts to restrain gene conversion and mutagenic
      single-strand annealing. We propose that USP48 promotes genome stability by
      antagonizing BRCA1 E3 ligase function.

PMID- 29335416
TI  - Lack of pronounced changes in the expression of fatty acid handling proteins in
      adipose tissue and plasma of morbidly obese humans.
AB  - BACKGROUND/OBJECTIVES: Fatty acid handling proteins are involved in the process
      of accumulation of lipids in different fat tissue depots. Thus, the aim of the
      study was to estimate the expression of both fatty acid transport and binding
      proteins in the subcutaneous (SAT) and visceral adipose tissue (VAT) of patients
      with morbid obesity without metabolic syndrome, as well as the plasma
      concentrations of these transporters. SUBJECTS/METHODS: Protein (Western
      blotting) and mRNA (Real-time PCR) expression of selected fatty acid handling
      proteins was assessed in the visceral and subcutaneous adipose tissue of 30
      patients with morbid obesity. The control group consisted of 10 lean age-matched
      patients. Plasma levels of fatty acid protein transporters were also evaluated
      using ELISA method. Moreover, total plasma fatty acid composition and
      concentration was determined by gas-liquid chromatography (GLC). RESULTS:
      Significant increase in fatty acid translocase (FAT/CD36) mRNA (P = 0.03) and
      plasmalemmal (P = 0.01) expression was observed in VAT of patients with morbid
      obesity vs. lean subjects together with elevation of lipoprotein lipase (LPL), as
      well as peroxisome proliferator-activated receptor gamma (PPARgamma) in both
      examined compartments of adipose tissue. Moreover, in obese subjects plasma
      concentration of RBP4 was markedly elevated (P = 0.04) and sCD36 level presented
      a tendency for an increase (P = 0.08) with concomitant lack of changes in FABP4
      concentration (P > 0.05). CONCLUSIONS: Fatty acid transport into adipocytes may
      be, at least in part, related to the increased expression of FAT/CD36 in the VAT
      of morbidly obese patients, which is accompanied by augmented expression of LPL,
      as well as PPARgamma. Probably, alternations in plasma concentrations of RBP4 and
      sCD36 in obese patients are associated with "unhealthy" fat distribution.

PMID- 29335417
TI  - Europe's lost forests: a pollen-based synthesis for the last 11,000 years.
AB  - 8000 years ago, prior to Neolithic agriculture, Europe was mostly a wooded
      continent. Since then, its forest cover has been progressively fragmented, so
      that today it covers less than half of Europe's land area, in many cases having
      been cleared to make way for fields and pasture-land. Establishing the origin of
      Europe's current, more open land-cover mosaic requires a long-term perspective,
      for which pollen analysis offers a key tool. In this study we utilise and compare
      three numerical approaches to transforming pollen data into past forest cover,
      drawing on >1000 14C-dated site records. All reconstructions highlight the
      different histories of the mixed temperate and the northern boreal forests, with
      the former declining progressively since ~6000 years ago, linked to forest
      clearance for agriculture in later prehistory (especially in northwest Europe)
      and early historic times (e.g. in north central Europe). In contrast, extensive
      human impact on the needle-leaf forests of northern Europe only becomes
      detectable in the last two millennia and has left a larger area of forest in
      place. Forest loss has been a dominant feature of Europe's landscape ecology in
      the second half of the current interglacial, with consequences for carbon
      cycling, ecosystem functioning and biodiversity.

PMID- 29335418
TI  - Gender-specific association of early age-related macular degeneration with
      systemic and genetic factors in a Japanese population.
AB  - The Tsuruoka Metabolomics Cohort Study included subjects aged 35-74 years from
      participants in annual health check-up programs in Tsuruoka, Japan. The gender
      specific associations of early age-related macular degeneration (AMD) with
      systemic and genetic factors was assessed cross-sectionally. Of these, 3,988
      subjects had fundus photographs of sufficient quality, and early AMD was present
      in 12.3% and 10.3% of men and women, respectively. In men, higher levels of high
      density lipoprotein cholesterol and lower levels of triglycerides were associated
      with increased odds of having early AMD after adjusting for potential risk
      factors (for each 1 mmol/L increase, odds ratio [OR]: 1.61 and 0.78, 95%
      confidence interval [CI]: 1.17-2.23 and 0.64-0.96, respectively). In women,
      higher levels of total cholesterol and low-density lipoprotein cholesterol were
      associated with increased risk of having early AMD (OR: 1.21 and 1.26, 95% CI:
      1.01-1.44 and 1.03-1.53, respectively). Sub-analysis demonstrated that women with
      ARMS2 A69S polymorphisms had a stronger risk for early AMD (OR: 3.25, 95% CI:
      2.10-5.04) than men (OR: 1.65, 95% CI: 1.02-2.69). Differential associations of
      early AMD with both systemic and genetic factors by sex were demonstrated in a
      Japanese cohort, which suggests that disease process of early AMD could be
      different by sex.

PMID- 29335419
TI  - A Global View of Transcriptome Dynamics During Male Floral Bud Development in
      Populus tomentosa.
AB  - To obtain a comprehensive overview of the dynamic transcriptome during male
      floral bud development in Populus tomentosa, high-throughput RNA-seq was
      conducted during eight flowering-related stages. Among the 109,212 de novo
      assembled unigenes, 6,959 were differentially expressed during the eight stages.
      The overrepresented classed of genes identified by Gene Ontology (GO) enrichment
      included 'response to environmental stimuli' and 'plant-type spore development'.
      One-third of the differentially expressed genes were transcription factors (TFs).
      Several genes and gene families were analyzed in depth, including MADS-box TFs,
      Squamosa promoter binding protein-like family, receptor-like kinases, FLOWERING
      LOCUS T/TERMINAL-FLOWER-LIKE 1 family, key genes involved in anther and tapetum
      development, as well as LEAFY, WUSCHEL and CONSTANS. The results provided new
      insights into the roles of these and other well known gene families during the
      annual flowering cycle. To explore the mechanisms regulating poplar flowering, a
      weighted gene co-expression network was constructed using 98 floral-related genes
      involved in flower meristem identity and flower development. Many modules of co
      expressed genes and hub genes were identified, such as APETALA1 and HUA1. This
      work provides many new insights on the annual flowering cycle in a perennial
      plant, and a major new resource for plant biology and biotechnology.

PMID- 29335420
TI  - Lamina Cribrosa Morphology Predicts Progressive Retinal Nerve Fiber Layer Loss In
      Eyes with Suspected Glaucoma.
AB  - Although early diagnosis and treatment reduce the risk of blindness from
      glaucoma, the decision on whether or not to begin treatment in patients with
      suspected glaucoma is often a dilemma because the majority of patients never
      develop definite glaucoma. A growing body of evidences suggests that posterior
      bowing of the lamina cribrosa (LC) is the earliest structural change preceding
      the retinal nerve fiber layer (RNFL) loss in glaucomatous optic neuropathy. Based
      on this notion, we conducted a prospective study enrolling 87 eyes suspected of
      having glaucoma to investigate whether the future rate of RNFL loss is associated
      with the baseline LC curve evaluated by measuring the LC curve index (LCCI) using
      enhanced depth imaging optical coherence tomography. A faster rate of RNFL loss
      was significantly associated with greater LCCI (P < 0.001;standardized
      coefficient beta = -0.392), older age (P = 0.008;beta = -0.314), and greater
      vertical cup-to-disc ratio (P = 0.040;beta = -0.233). Assessment of LC morphology
      may help predict the disease outcome in eyes with suspected glaucoma.

PMID- 29335421
TI  - Hydroacoustics as a tool to examine the effects of Marine Protected Areas and
      habitat type on marine fish communities.
AB  - Hydroacoustic technologies are widely used in fisheries research but few studies
      have used them to examine the effects of Marine Protected Areas (MPAs). We
      evaluate the efficacy of hydroacoustics to examine the effects of closure to
      fishing and habitat type on fish populations in the Cabo Pulmo National Park
      (CPNP), Mexico, and compare these methods to Underwater Visual Censuses (UVC).
      Fish density, biomass and size were all significantly higher inside the CPNP
      (299%, 144% and 52% respectively) than outside in non-MPA control areas. These
      values were much higher when only accounting for the reefs within the CPNP
      (4715%, 6970% and 97% respectively) highlighting the importance of both habitat
      complexity and protection from fishing for fish populations. Acoustic estimates
      of fish biomass over reef-specific sites did not differ significantly from those
      estimated using UVC data, although acoustic densities were less due to higher
      numbers of small fish recorded by UVC. There is thus considerable merit in
      nesting UVC surveys, also providing species information, within hydroacoustic
      surveys. This study is a valuable starting point in demonstrating the utility of
      hydroacoustics to assess the effects of coastal MPAs on fish populations,
      something that has been underutilised in MPA design, formation and management.

PMID- 29335422
TI  - Lifetime-preserving reference models for characterizing spreading dynamics on
      temporal networks.
AB  - To study how a certain network feature affects processes occurring on a temporal
      network, one often compares properties of the original network against those of a
      randomized reference model that lacks the feature in question. The randomly
      permuted times (PT) reference model is widely used to probe how temporal features
      affect spreading dynamics on temporal networks. However, PT implicitly assumes
      that edges and nodes are continuously active during the network sampling period -
      an assumption that does not always hold in real networks. We systematically
      analyze a recently-proposed restriction of PT that preserves node lifetimes
      (PTN), and a similar restriction (PTE) that also preserves edge lifetimes. We use
      PT, PTN, and PTE to characterize spreading dynamics on (i) synthetic networks
      with heterogeneous edge lifespans and tunable burstiness, and (ii) four real
      world networks, including two in which nodes enter and leave the network
      dynamically. We find that predictions of spreading speed can change considerably
      with the choice of reference model. Moreover, the degree of disparity in the
      predictions reflects the extent of node/edge turnover, highlighting the
      importance of using lifetime-preserving reference models when nodes or edges are
      not continuously present in the network.

PMID- 29335423
TI  - Evaluation of the effects of space allowance on measures of animal welfare in
      laboratory mice.
AB  - We studied how space allowance affects measures of animal welfare in mice by
      systematically varying group size and cage type across three levels each in both
      males and females of two strains of mice (C57BL/6ByJ and BALB/cByJ; n = 216
      cages, a total of 1152 mice). This allowed us to disentangle the effects of total
      floor area, group size, stocking density, and individual space allocation on a
      broad range of measures of welfare, including growth (food and water intake, body
      mass); stress physiology (glucocorticoid metabolites in faecal boli);
      emotionality (open field behaviour); brain function (recurrent perseveration in a
      two-choice guessing task); and home-cage behaviour (activity, stereotypic
      behaviour). While increasing group size was associated with a decrease in food
      and water intake in general, and more specifically with increased attrition due
      to escalated aggression in male BALB mice, no other consistent effects of any
      aspect of space allowance were found with respect to the measures studied here.
      Our results indicate that within the range of conditions commonly found in
      laboratory mouse housing, space allowance as such has little impact on measures
      of welfare, except for group size which may be a risk factor for escalating
      aggression in males of some strains.

PMID- 29335424
TI  - Functionalisation of Detonation Nanodiamond for Monodispersed, Soluble DNA
      Nanodiamond Conjugates Using Mixed Silane Bead-Assisted Sonication
      Disintegration.
AB  - Nanodiamonds have many attractive properties that make them suitable for a range
      of biological applications, but their practical use has been limited because
      nanodiamond conjugates tend to aggregate in solution during or after
      functionalisation. Here we demonstrate the production of DNA-detonation
      nanodiamond (DNA-DND) conjugates with high dispersion and solubility using an
      ultrasonic, mixed-silanization chemistry protocol based on the in situ Bead
      Assisted Sonication Disintegration (BASD) silanization method. We use two silanes
      to achieve these properties: (1) 3-(trihydroxysilyl)propyl methylphosphonate
      (THPMP); a negatively charged silane that imparts high zeta potential and
      solubility in solution; and (2) (3-aminopropyl)triethoxysilane (APTES); a
      commonly used functional silane that contributes an amino group for subsequent
      bioconjugation. We target these amino groups for covalent conjugation to
      thiolated, single-stranded DNA oligomers using the heterobifunctional crosslinker
      sulfosuccinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate (Sulfo-SMCC).
      The resulting DNA-DND conjugates are the smallest reported to date, as determined
      by Dynamic Light Scattering (DLS) and Atomic Force Microscopy (AFM). The
      functionalisation method we describe is versatile and can be used to produce a
      wide variety of soluble DND-biomolecule conjugates.

PMID- 29335426
TI  - Author Correction: Intensification of terrestrial carbon cycle related to El Nino
      Southern Oscillation under greenhouse warming.
AB  - In the original version of this Article, the affiliation for Su-Jon Jeong was
      incorrectly given as 'Southern University of Science and Technology of China
      (SUSTECH)', instead of 'Southern University of Science and Technology (SUSTECH)'.
      This has now been corrected in both the PDF and HTML versions of the Article.

PMID- 29335425
TI  - SPARC expression is associated with hepatic injury in rodents and humans with non
      alcoholic fatty liver disease.
AB  - Mechanisms that control progression from simple steatosis to steato-hepatitis and
      fibrosis in patients with non-alcoholic fatty liver disease (NAFLD) are unknown.
      SPARC, a secreted matricellular protein, is over-expressed in the liver under
      chronic injury. Contribution of SPARC accumulation to disease severity is largely
      unknown in NAFLD. We assessed the hypothesis that SPARC is increased in livers
      with more necrosis and inflammation and could be associated with more fibrosis.
      qrt-PCR, immunohistochemistry, and ELISA were employed to localize and quantify
      changes in SPARC in 62 morbidly obese patients with NAFLD/NASH and in a mouse
      model of diet-induced-NASH. Results were correlated with the severity of
      NAFLD/NASH. In obese patients 2 subgroups were identified with either high SPARC
      expression (n = 16) or low SPARC expression (n = 46) in the liver, with a cutoff
      of 1.2 fold expression. High expression of SPARC paralleled hepatocellular damage
      and increased mRNA expression of pro-fibrogenic factors in the liver. In line
      with these findings, in the NASH animal model SPARC knockout mice were protected
      from inflammatory injury, and showed less inflammation and fibrosis. Hepatic
      SPARC expression is associated with liver injury and fibrogenic processes in
      NAFLD. SPARC has potential as preventive or therapeutic target in NAFLD patients.

PMID- 29335427
TI  - Chronic alcohol exposure disrupts top-down control over basal ganglia action
      selection to produce habits.
AB  - Addiction involves a predominance of habitual control mediated through action
      selection processes in dorsal striatum. Research has largely focused on neural
      mechanisms mediating a proposed progression from ventral to dorsal lateral
      striatal control in addiction. However, over reliance on habit striatal processes
      may also arise from reduced cortical input to striatum, thereby disrupting
      executive control over action selection. Here, we identify novel mechanisms
      through which chronic intermittent ethanol exposure and withdrawal (CIE) disrupts
      top-down control over goal-directed action selection processes to produce habits.
      We find CIE results in decreased excitability of orbital frontal cortex (OFC)
      excitatory circuits supporting goal-directed control, and, strikingly,
      selectively reduces OFC output to the direct output pathway in dorsal medial
      striatum. Increasing the activity of OFC circuits restores goal-directed control
      in CIE-exposed mice. Our findings show habitual control in alcohol dependence can
      arise through disrupted communication between top-down, goal-directed processes
      onto basal ganglia pathways controlling action selection.

PMID- 29335428
TI  - Analysis of the HIV-2 protease's adaptation to various ligands: characterization
      of backbone asymmetry using a structural alphabet.
AB  - The HIV-2 protease (PR2) is a homodimer of 99 residues with asymmetric assembly
      and binding various ligands. We propose an exhaustive study of the local
      structural asymmetry between the two monomers of all available PR2 structures
      complexed with various inhibitors using a structural alphabet approach. On
      average, PR2 exhibits asymmetry in 31% of its positions-i.e., exhibiting
      different backbone local conformations in the two monomers. This asymmetry was
      observed all along its structure, particularly in the elbow and flap regions. We
      first differentiated structural asymmetry conserved in most PR2 structures from
      the one specific to some PR2. Then, we explored the origin of the detected
      asymmetry in PR2. We localized asymmetry that could be induced by PR2's
      flexibility, allowing transition from the semi-open to closed conformations and
      the asymmetry potentially induced by ligand binding. This latter could be
      important for the PR2's adaptation to diverse ligands. Our results highlighted
      some differences between asymmetry of PR2 bound to darunavir and amprenavir that
      could explain their differences of affinity. This knowledge is critical for a
      better description of PR2's recognition and adaptation to various ligands and for
      a better understanding of the resistance of PR2 to most PR2 inhibitors, a major
      antiretroviral class.

PMID- 29335429
TI  - RFA Guardian: Comprehensive Simulation of Radiofrequency Ablation Treatment of
      Liver Tumors.
AB  - The RFA Guardian is a comprehensive application for high-performance patient
      specific simulation of radiofrequency ablation of liver tumors. We address a wide
      range of usage scenarios. These include pre-interventional planning, sampling of
      the parameter space for uncertainty estimation, treatment evaluation and, in the
      worst case, failure analysis. The RFA Guardian is the first of its kind that
      exhibits sufficient performance for simulating treatment outcomes during the
      intervention. We achieve this by combining a large number of high-performance
      image processing, biomechanical simulation and visualization techniques into a
      generalized technical workflow. Further, we wrap the feature set into a single,
      integrated application, which exploits all available resources of standard
      consumer hardware, including massively parallel computing on graphics processing
      units. This allows us to predict or reproduce treatment outcomes on a single
      personal computer with high computational performance and high accuracy. The
      resulting low demand for infrastructure enables easy and cost-efficient
      integration into the clinical routine. We present a number of evaluation cases
      from the clinical practice where users performed the whole technical workflow
      from patient-specific modeling to final validation and highlight the
      opportunities arising from our fast, accurate prediction techniques.

PMID- 29335430
TI  - Transspinal Direct Current Stimulation Produces Persistent Plasticity in Human
      Motor Pathways.
AB  - The spinal cord is an integration center for descending, ascending, and segmental
      neural signals. Noninvasive transspinal stimulation may thus constitute an
      effective method for concomitant modulation of local and distal neural circuits.
      In this study, we established changes in cortical excitability and input/output
      function of corticospinal and spinal neural circuits before, at 0-15 and at 30-45
      minutes after cathodal, anodal, and sham transspinal direct current stimulation
      (tsDCS) to the thoracic region in healthy individuals. We found that
      intracortical inhibition was different among stimulation polarities, however
      remained unchanged over time. Intracortical facilitation increased after cathodal
      and anodal tsDCS delivered with subjects seated, and decreased after cathodal
      tsDCS delivered with subjects lying supine. Both cathodal and anodal tsDCS
      increased corticospinal excitability, yet facilitation was larger and persisted
      for 30 minutes post stimulation only when cathodal tsDCS was delivered with
      subjects lying supine. Spinal input/output reflex function was decreased by
      cathodal and not anodal tsDCS. These changes may be attributed to altered
      spontaneous neural activity and membrane potentials of corticomotoneuronal cells
      by tsDCS involving similar mechanisms to those mediating motor learning. Our
      findings indicate that thoracic tsDCS has the ability to concomitantly alter
      cortical, corticospinal, and spinal motor output in humans.

PMID- 29335431
TI  - Synaptic localisation of SRF coactivators, MKL1 and MKL2, and their role in
      dendritic spine morphology.
AB  - The megakaryoblastic leukaemia (MKL) family are serum response factor (SRF)
      coactivators, which are highly expressed in the brain. Accordingly, MKL plays
      important roles in dendritic morphology, neuronal migration, and brain
      development. Further, nucleotide substitutions in the MKL1 and MKL2 genes are
      found in patients with schizophrenia and autism spectrum disorder, respectively.
      Thus, studies on the precise synaptic localisation and function of MKL in neurons
      are warranted. In this study, we generated and tested new antibodies that
      specifically recognise endogenously expressed MKL1 and MKL2 proteins in neurons.
      Using these reagents, we biochemically and immunocytochemically show that MKL1
      and MKL2 are localised at synapses. Furthermore, shRNA experiments revealed that
      postsynaptic deletion of MKL1 or MKL2 reduced the percentage of mushroom- or
      stubby-type spines in cultured neurons. Taken together, our findings suggest that
      MKL1 and MKL2 are present at synapses and involved in dendritic spine maturation.
      This study may, at least in part, contribute to better understanding of the
      molecular mechanisms underlying MKL-mediated synaptic plasticity and neurological
      disorders.

PMID- 29335432
TI  - The relationship of dietary fish intake to diabetic retinopathy and retinal
      vascular caliber in patients with type 2 diabetes.
AB  - In this cross-sectional study, we evaluated the association of dietary fish
      intake with varying severity of diabetic retinopathy (DR) and retinal vascular
      caliber in Asians with type 2 diabetes mellitus. 357 Asians (median age: 58
      years; 31% women; 78% Chinese) were recruited from a tertiary eye care
      institution in Singapore. Fish consumption was evaluated using a validated food
      frequency questionnaire. Digital retinal photographs assessed for DR severity and
      retinal vascular caliber. Ordered logistic and linear regression models were used
      to investigate the association of fish intake with DR severity and vascular
      caliber. Increasing frequency of fish consumption was significantly associated
      with lower odds of having severe DR (odds ratio [OR] = 0.91, 95% CI: 0.84-0.99
      per 1-unit increase of fish intake; P = 0.038). Among those with no retinopathy,
      persons in quartile 4 fish intake had a wider retinal vascular caliber for
      arteriolar (beta = 22.27 um, 95% CI: 12.64-31.90; P-trend < 0.001) and venular
      (beta = 32.00 um, 95% CI: 17.56-46.43; P-trend < 0.001), than those in quartile 1
      fish intake. Persons with higher fish intake had a decreased likelihood of having
      severe DR. In diabetics without retinopathy, higher fish intake was associated
      with wider retinal vascular caliber. Future research is needed to reinforce the
      direction of the casualty.

PMID- 29335433
TI  - Conformational Landscape of the PRKACA-DNAJB1 Chimeric Kinase, the Driver for
      Fibrolamellar Hepatocellular Carcinoma.
AB  - In fibrolamellar hepatocellular carcinoma a single genetic deletion results in
      the fusion of the first exon of the heat shock protein 40, DNAJB1, which encodes
      the J domain, with exons 2-10 of the catalytic subunit of protein kinase A,
      PRKACA. This produces an enzymatically active chimeric protein J-PKAcalpha. We
      used molecular dynamics simulations and NMR to analyze the conformational
      landscape of native and chimeric kinase, and found an ensemble of conformations.
      These ranged from having the J-domain tucked under the large lobe of the kinase,
      similar to what was reported in the crystal structure, to others where the J
      domain was dislodged from the core of the kinase and swinging free in solution.
      These simulated dislodged states were experimentally captured by NMR. Modeling of
      the different conformations revealed no obvious steric interactions of the J
      domain with the rest of the RIIbeta holoenzyme.

PMID- 29335434
TI  - Competitive influence maximization and enhancement of synchronization in
      populations of non-identical Kuramoto oscillators.
AB  - Many networked systems have evolved to optimize performance of function. Much
      literature has considered optimization of networks by central planning, but
      investigations of network formation amongst agents connecting to achieve non
      aligned goals are comparatively rare. Here we consider the dynamics of
      synchronization in populations of coupled non-identical oscillators and analyze
      adaptations in which individual nodes attempt to rewire network topology to
      optimize node-specific aims. We demonstrate that, even though individual nodes'
      goals differ very widely, rewiring rules in which each node attempts to connect
      to the rest of the network in such a way as to maximize its influence on the
      system can enhance synchronization of the collective. The observed speed-up of
      consensus finding in this competitive dynamics might explain enhanced
      synchronization in real world systems and shed light on mechanisms for improved
      consensus finding in society.

PMID- 29335435
TI  - Placental Morphology Is Associated with Maternal Depressive Symptoms during
      Pregnancy and Toddler Psychiatric Problems.
AB  - Maternal depressive symptoms during pregnancy predict increased psychiatric
      problems in children. The underlying biological mechanisms remain unclear. Hence,
      we examined whether alterations in the morphology of 88 term placentas were
      associated with maternal depressive symptoms during pregnancy and psychiatric
      problems in 1.9-3.1-years old (Mean = 2.1 years) toddlers. Maternal depressive
      symptoms were rated biweekly during pregnancy with the Center of Epidemiological
      Studies Depression Scale (n = 86). Toddler psychiatric problems were mother-rated
      with the Child Behavior Checklist (n = 60). We found that higher maternal
      depressive symptoms throughout pregnancy [B = -0.24 Standard Deviation (SD)
      units: 95% Confidence Interval (CI) = -0.46; -0.03: P = 0.03; Mean difference = 
      0.66 SDs; 95% CI = -0.08; -1.23: P = 0.03; between those with and without
      clinically relevant depressive symptoms] were associated with lower variability
      in the placental villous barrier thickness of gamma-smooth muscle actin-negative
      villi. This placental morphological change predicted higher total (B = -0.34 SDs:
      95% CI = -0.60; -0.07: P = 0.01) and internalizing (B = -0.32 SDs: 95% CI = 
      0.56; -0.08: P = 0.01) psychiatric problems in toddlers. To conclude, our
      findings suggest that both maternal depressive symptoms during pregnancy and
      toddler psychiatric problems may be associated with lower variability in the
      villous membrane thickness of peripheral villi in term placentas. This lower
      heterogeneity may compromise materno-fetal exchange, suggesting a possible role
      for altered placental morphology in the fetal programming of mental disorders.

PMID- 29335436
TI  - Deregulated PP1alpha phosphatase activity towards MAPK activation is antagonized
      by a tumor suppressive failsafe mechanism.
AB  - The mitogen-activated protein kinase (MAPK) pathway is frequently aberrantly
      activated in advanced cancers, including metastatic prostate cancer (CaP).
      However, activating mutations or gene rearrangements among MAPK signaling
      components, such as Ras and Raf, are not always observed in cancers with
      hyperactivated MAPK. The mechanisms underlying MAPK activation in these cancers
      remain largely elusive. Here we discover that genomic amplification of the PPP1CA
      gene is highly enriched in metastatic human CaP. We further identify an
      S6K/PP1alpha/B-Raf signaling pathway leading to activation of MAPK signaling that
      is antagonized by the PML tumor suppressor. Mechanistically, we find that
      PP1alpha acts as a B-Raf activating phosphatase and that PML suppresses MAPK
      activation by sequestering PP1alpha into PML nuclear bodies, hence repressing S6K
      dependent PP1alpha phosphorylation, 14-3-3 binding and cytoplasmic accumulation.
      Our findings therefore reveal a PP1alpha/PML molecular network that is
      genetically altered in human cancer towards aberrant MAPK activation, with
      important therapeutic implications.

PMID- 29335437
TI  - Deubiquitinase USP13 dictates MCL1 stability and sensitivity to BH3 mimetic
      inhibitors.
AB  - MCL1 is a pivot member of the anti-apoptotic BCL-2 family proteins. While a
      distinctive feature of MCL1 resides in its efficient ubiquitination and
      destruction, the deubiquitinase USP9X has been implicated in the preservation of
      MCL1 expression by removing the polyubiquitin chains. Here we perform an unbiased
      siRNA screen and identify that the second deubiquitinase, USP13, regulates MCL1
      stability in lung and ovarian cancer cells. Mechanistically, USP13 interacts with
      and stabilizes MCL1 via deubiquitination. As a result, USP13 depletion using
      CRISPR/Cas9 nuclease system inhibits tumor growth in xenografted nude mice. We
      further report that genetic or pharmacological inhibition of USP13 considerably
      reduces MCL1 protein abundance and significantly increases tumor cell sensitivity
      to BH3 mimetic inhibitors targeting BCL-2 and BCL-XL. Collectively, we nominate
      USP13 as a novel deubiquitinase which regulates MCL1 turnover in diverse solid
      tumors and propose that USP13 may be a potential therapeutic target for the
      treatment of various malignancies.

PMID- 29335439
TI  - Net global warming potential and greenhouse gas intensity as affected by
      different water management strategies in Chinese double rice-cropping systems.
AB  - This study provides a complete account of global warming potential (GWP) and
      greenhouse gas intensity (GHGI) in relation to a long-term water management
      experiment in Chinese double-rice cropping systems. The three strategies of water
      management comprised continuous (year-round) flooding (CF), flooding during the
      rice season but with drainage during the midseason and harvest time (F-D-F), and
      irrigation only for flooding during transplanting and the tillering stage (F-RF).
      The CH4 and N2O fluxes were measured with the static chamber method. Soil organic
      carbon (SOC) sequestration rates were estimated based on the changes in the
      carbon stocks during 1998-2014. Longer periods of soil flooding led to increased
      CH4 emissions, reduced N2O emissions, and enhanced SOC sequestration. The net
      GWPs were 22,497, 8,895, and 1,646 kg CO2-equivalent ha-1 yr-1 for the CF, F-D-F,
      and F-RF, respectively. The annual rice grain yields were comparable between the
      F-D-F and CF, but were reduced significantly (by 13%) in the F-RF. The GHGIs were
      2.07, 0.87, and 0.18 kg CO2-equivalent kg-1 grain yr-1 for the CF, F-D-F, and F
      RF, respectively. These results suggest that F-D-F could be used to maintain the
      grain yields and simultaneously mitigate the climatic impact of double rice
      cropping systems.

PMID- 29335440
TI  - Co-action equilibrium fails to predict choices in mixed-strategy settings.
AB  - Social projection is the tendency to project one's own characteristics onto
      others. This phenomenon can potentially explain cooperation in prisoner's dilemma
      experiments and other social dilemmas. The social projection hypothesis has
      recently been formalized for symmetric games as co-action equilibrium and for
      general games as consistent evidential equilibrium. These concepts have been
      proposed to predict choice behavior in experimental one-shot games. We test the
      predictions of the co-action equilibrium concept in a simple binary minimizer
      game experiment. We find no evidence of social projection.

PMID- 29335438
TI  - Grey and white matter volumes either in treatment-naive or hormone-treated
      transgender women: a voxel-based morphometry study.
AB  - Many previous magnetic resonance imaging (MRI) studies have documented sex
      differences in brain morphology, but the patterns of sexual brain differences in
      transgender women - male sex assigned at birth - with a diagnosis of gender
      dysphoria (TW) have been rarely investigated to date. We acquired T1-weighted MRI
      data for the following four (n = 80) groups: treatment-naive TW (TNTW), TW
      treated with cross-sex hormones for at least one year (TTW), cisgender men, and
      cisgender women (cisgender individuals as controls). Differences in whole-brain
      and regional white matter volume and grey matter volume (GMV) were assessed using
      voxel-based morphometry. We found lower global brain volumes and regional GMVs in
      a large portion of the posterior-superior frontal cortex in the cisgender women
      group than in the TTW and cisgender men groups. Additionally, both transgender
      groups exhibited lower bilateral insular GMVs than the cisgender women group. Our
      results highlight differences in the insula in both transgender groups; such
      differences may be characteristic of TW. Furthermore, these alterations in the
      insula could be related to the neural network of body perception and reflect the
      distress that accompanies gender dysphoria.

PMID- 29335441
TI  - A Collective Route to Head and Neck Cancer Metastasis.
AB  - Distant metastasis (DM) from head and neck cancers (HNC) portends a poor patient
      prognosis. Despite its important biological role, little is known about the cells
      which seed these DM. Circulating tumour cells (CTCs) represent a transient cancer
      cell population, which circulate in HNC patients' peripheral blood and seed at
      distant sites. Capture and analysis of CTCs offers insights into tumour
      metastasis and can facilitate treatment strategies. Whilst the data on singular
      CTCs have shown clinical significance, the role of CTC clusters in metastasis
      remains limited. In this pilot study, we assessed 60 treatment naive HNC patients
      for CTCs with disease ranging from early to advanced stages, for CTC clusters
      utilizing spiral CTC enrichment technology. Single CTCs were isolated in 18/60
      30% (Ranging from Stage I-IV), CTC clusters in 15/60-25% (exclusively Stage IV)
      with 3/15-20% of CTC clusters also containing leukocytes. The presence of CTC
      clusters associated with the development of distant metastatic disease(P =
      0.0313). This study demonstrates that CTC clusters are found in locally advanced
      patients, and this may be an important prognostic marker. In vivo and in vitro
      studies are warranted to determine the role of these CTC clusters, in particular,
      whether leukocyte involvement in CTC clusters has clinical relevance.

PMID- 29335442
TI  - Nanostructural Differentiation and Toxicity of Amyloid-beta25-35 Aggregates Ensue
      from Distinct Secondary Conformation.
AB  - Amyloid nanostructures are originated from protein misfolding and aberrant
      aggregation, which is associated with the pathogenesis of many types of
      degenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD)
      and Huntington's disease. The secondary conformation of peptides is of a
      fundamental importance for aggregation and toxicity of amyloid peptides. In this
      work, Abeta25-35, a fragment of amyloid beta(1-42) (Abeta42), was selected to
      investigate the correlation between secondary structures and toxicity of amyloid
      fibrils. Furthermore, each aggregation assemblies show different cell membrane
      disruption and cytotoxicity. The structural analysis of amyloid aggregates
      originated from different secondary structure motifs is helpful to understand the
      mechanism of peptides/cell interactions in the pathogenesis of amyloid diseases.

PMID- 29335444
TI  - A Geodetic Strain Rate Model for the East African Rift System.
AB  - Here we describe the new Sub-Saharan Africa Geodetic Strain Rate Model v.1.0 (SSA
      GSRM v.1.0), which provides fundamental constraints on long-term tectonic
      deformation in the region and an improved seismic hazards assessment in Sub
      Saharan Africa. Sub-Saharan Africa encompasses the East African Rift System, the
      active divergent plate boundary between the Nubian and Somalian plates, where
      strain is largely accommodated along the boundaries of three subplates. We
      develop an improved geodetic strain rate field for sub-Saharan Africa that
      incorporates 1) an expanded geodetic velocity field, 2) redefined regions of
      deforming zones guided by seismicity distribution, and 3) updated constraints on
      block rotations. SSA-GSRM v.1.0 spans longitudes 22 degrees  to 55.5 degrees  and
      latitudes -52 degrees  to 20 degrees  with 0.25 degrees  (longitude) by 0.2
      degrees  (latitude) spacing. For plates/sub-plates, we assign rigid block
      rotations as constraints on the strain rate calculation that is determined by
      fitting bicubic Bessel splines to a new geodetic velocity solution for an
      interpolated velocity gradient tensor field. We derive strain rates, velocities,
      and vorticity rates from the velocity gradient tensor field. A comparison with
      the Global Geodetic Strain Rate model v2.1 reveals regions of previously
      unresolved spatial heterogeneities in geodetic strain rate distribution, which
      indicates zones of elevated seismic risk.

PMID- 29335443
TI  - Elucidating the genomic architecture of Asian EGFR-mutant lung adenocarcinoma
      through multi-region exome sequencing.
AB  - EGFR-mutant lung adenocarcinomas (LUAD) display diverse clinical trajectories and
      are characterized by rapid but short-lived responses to EGFR tyrosine kinase
      inhibitors (TKIs). Through sequencing of 79 spatially distinct regions from 16
      early stage tumors, we show that despite low mutation burdens, EGFR-mutant Asian
      LUADs unexpectedly exhibit a complex genomic landscape with frequent and early
      whole-genome doubling, aneuploidy, and high clonal diversity. Multiple truncal
      alterations, including TP53 mutations and loss of CDKN2A and RB1, converge on
      cell cycle dysregulation, with late sector-specific high-amplitude amplifications
      and deletions that potentially beget drug resistant clones. We highlight the
      association between genomic architecture and clinical phenotypes, such as co
      occurring truncal drivers and primary TKI resistance. Through comparative
      analysis with published smoking-related LUAD, we postulate that the high intra
      tumor heterogeneity observed in Asian EGFR-mutant LUAD may be contributed by an
      early dominant driver, genomic instability, and low background mutation rates.

PMID- 29335445
TI  - Trophic ecology of glass sponge reefs in the Strait of Georgia, British Columbia.
AB  - Sponges link the microbial loop with benthic communities by feeding on bacteria.
      Glass sponge reefs on the continental shelf of western Canada have extremely high
      grazing rates, consuming seven times more particulate carbon than can be supplied
      by vertical flux alone. Unlike many sponges, the reef building species
      Aphrocallistes vastus has no microbial symbionts and removes little dissolved
      organic carbon. To determine how reef sponges therefore get enough food to
      sustain such substantial grazing we measured stable carbon and nitrogen isotope
      signatures of water, sediment and sponge tissues. To ensure samples were
      temporally associated, we also studied the duration particles were retained in
      tissues in controlled feeding studies using microscopic beads and 13C-labeled
      bacteria. Although fecal pellets were expelled from sponges within 24 hours of
      feeding, intact bacteria were still found in tissues and sponge tissues retained
      elevated 13C levels for at least 14 days. These independent lines of evidence
      suggest that carbon in reef sponge tissues may reflect food consumed from days to
      weeks earlier. Stable isotope analysis suggests that heterotrophic bacteria
      ingested by the sponges comes from a confluence of trophic subsidies: from
      terrestrial and oceanic sources, and also potentially on sediment-borne bacteria
      resuspended by tidal currents.

PMID- 29335446
TI  - Experimental quantum simulation of fermion-antifermion scattering via boson
      exchange in a trapped ion.
AB  - Quantum field theories describe a variety of fundamental phenomena in physics.
      However, their study often involves cumbersome numerical simulations. Quantum
      simulators, on the other hand, may outperform classical computational capacities
      due to their potential scalability. Here we report an experimental realization of
      a quantum simulation of fermion-antifermion scattering mediated by bosonic modes,
      using a multilevel trapped ion, which is a simplified model of fermion scattering
      in both perturbative and non-perturbative quantum electrodynamics. The simulated
      model exhibits prototypical features in quantum field theory including particle
      pair creation and annihilation, as well as self-energy interactions. These are
      experimentally observed by manipulating four internal levels of a 171Yb+ trapped
      ion, where we encode the fermionic modes, and two motional degrees of freedom
      that simulate the bosonic modes. Our experiment establishes an avenue towards the
      efficient implementation of field modes, which may prove useful in studies of
      quantum field theories including non-perturbative regimes.

PMID- 29335447
TI  - Exposure to famine in early life and chronic kidney diseases in adulthood.
AB  - OBJECTIVE: Chronic kidney disease (CKD) is an increasing contributor to the
      global disease burden. Previous findings indicated that exposure to famine in
      early life was associated with various metabolic diseases and urinary protein
      levels. We aimed to assess whether the exposure to China's Great Famine 1959-1962
      during fetal or childhood period was associated with glomerular filtration rate
      (GFR) and risk of CKD (eGFR<60 mL/min per 1.73 m2) in adulthood. MATERIALS AND
      METHODS: SPECT-China was a population-based observational study in 2014-2015.
      Totally, 5124 women were included from SPECT-China study. Based on the birth
      year, they were divided into fetal-exposed (1959-1962), childhood-exposed (1949
      1958), adolescence/young adult-exposed (1921-1948), and non-exposed (1963-1974,
      reference). The estimated glomerular filtration rate (eGFR) was calculated
      according to the Chronic Kidney Disease Epidemiology Collaboration equation. CKD
      was defined as eGFR less than 60 mL/min per 1.73 m2. RESULTS: Compared with the
      non-exposed, fetal exposure to famine was significantly associated with lower
      eGFR (B -1.47, 95%CI -2.81, -1.13) and greater risk of having CKD (OR 2.85, 95%CI
      1.25, 6.50) in the crude model adjusting age. Further adjustments for demographic
      variables, body mass index, diabetes, and blood pressure did not qualitatively
      change the association (eGFR B -1.35, 95%CI -2.67, -0.04; CKD OR 2.42, 95%CI
      1.05, 5.58). This association was not found in childhood-exposed and
      adolescence/young adult-exposed individuals. CONCLUSIONS: Prenatal exposure to
      famine may have long-term effects on declined GFR and the development of CKD in
      humans. thus, fetal stage may be an important time window to prevent CKD in later
      life.

PMID- 29335448
TI  - Regional evaluation of childhood acute lymphoblastic leukemia genetic
      susceptibility loci among Japanese.
AB  - Genome-wide association studies (GWAS) performed mostly in populations of
      European and Hispanic ancestry have confirmed an inherited genetic basis for
      childhood acute lymphoblastic leukemia (ALL), but these associations are less
      clear in other races/ethnicities. DNA samples from ALL patients (aged 0-19 years)
      previously enrolled onto a Tokyo Children's Cancer Study Group trial were
      collected during 2013-2015, and underwent single nucleotide polymorphism (SNP)
      microarray genotyping resulting in 527 B-cell ALL for analysis. Cases and control
      data for 3,882 samples from the Nagahama Study Group and Aichi Cancer Center
      Study were combined, and association analyses across 10 previous GWAS-identified
      regions were performed after targeted SNP imputation. Linkage disequilibrium (LD)
      patterns in Japanese and other populations were evaluated using the varLD score
      based on 1000 Genomes data. Risk associations for ARID5B (rs10821936, OR = 1.84,
      P = 6 * 10-17) and PIP4K2A (rs7088318, OR = 0.76, P = 2 * 10-4) directly
      transferred to Japanese, and the IKZF1 association was detected by an alternate
      SNP (rs1451367, OR = 1.52, P = 2 * 10-6). Marked regional LD differences between
      Japanese and Europeans was observed for most of the remaining loci for which
      associations did not transfer, including CEBPE, CDKN2A, CDKN2B, and ELK3. This
      study represents a first step towards characterizing the role of genetic
      susceptibility in childhood ALL risk in Japanese.

PMID- 29335449
TI  - Transcriptome profile of NO-induced Arabidopsis transcription factor genes
      suggests their putative regulatory role in multiple biological processes.
AB  - TFs are important proteins regulating plant responses during environmental
      stresses. These insults typically induce changes in cellular redox tone driven in
      part by promoting the production of reactive nitrogen species (RNS). The main
      source of these RNS is nitric oxide (NO), which serves as a signalling molecule,
      eliciting defence and resistance responses. To understand how these signalling
      molecules regulate key biological processes, we performed a large scale S
      nitrosocysteine (CySNO)-mediated RNA-seq analysis. The DEGs were analysed to
      identify potential regulatory TFs. We found a total of 673 (up- and down
      regulated) TFs representing a broad range of TF families. GO-enrichment and
      MapMan analysis suggests that more than 98% of TFs were mapped to the Arabidopsis
      thaliana genome and classified into pathways like hormone signalling, protein
      degradation, development, biotic and abiotic stress, etc. A functional analysis
      of three randomly selected TFs, DDF1, RAP2.6, and AtMYB48 identified a regulatory
      role in plant growth and immunity. Loss-of-function mutations within DDF1 and
      RAP2.6 showed compromised basal defence and effector triggered immunity,
      suggesting their positive role in two major plant defence systems. Together,
      these results imply an important data representing NO-responsive TFs that will
      help in exploring the core mechanisms involved in biological processes in plants.

PMID- 29335452
TI  - Chaotic universe model.
AB  - In this study, we consider nonlinear interactions between components such as dark
      energy, dark matter, matter and radiation in the framework of the Friedman
      Robertson-Walker space-time and propose a simple interaction model based on the
      time evolution of the densities of these components. By using this model we show
      that these interactions can be given by Lotka-Volterra type equations. We
      numerically solve these coupling equations and show that interaction dynamics
      between dark energy-dark matter-matter or dark energy-dark matter-matter
      radiation has a strange attractor for 0 > w de  >-1, w dm  >= 0, w m  >= 0 and w
      r  >= 0 values. These strange attractors with the positive Lyapunov exponent
      clearly show that chaotic dynamics appears in the time evolution of the
      densities. These results provide that the time evolution of the universe is
      chaotic. The present model may have potential to solve some of the cosmological
      problems such as the singularity, cosmic coincidence, big crunch, big rip,
      horizon, oscillation, the emergence of the galaxies, matter distribution and
      large-scale organization of the universe. The model also connects between
      dynamics of the competing species in biological systems and dynamics of the time
      evolution of the universe and offers a new perspective and a new different
      scenario for the universe evolution.

PMID- 29335450
TI  - Copper sulfide nanoparticles as a photothermal switch for TRPV1 signaling to
      attenuate atherosclerosis.
AB  - Atherosclerosis is characterized by the accumulation of lipids within the
      arterial wall. Although activation of TRPV1 cation channels by capsaicin may
      reduce lipid storage and the formation of atherosclerotic lesions, a clinical use
      for capsaicin has been limited by its chronic toxicity. Here we show that
      coupling of copper sulfide (CuS) nanoparticles to antibodies targeting TRPV1 act
      as a photothermal switch for TRPV1 signaling in vascular smooth muscle cells
      (VSMCs) using near-infrared light. Upon irradiation, local increases of
      temperature open thermo-sensitive TRPV1 channels and cause Ca2+ influx. The
      increase in intracellular Ca2+ activates autophagy and impedes foam cell
      formation in VSMCs treated with oxidized low-density lipoprotein. In vivo, CuS
      TRPV1 allows photoacoustic imaging of the cardiac vasculature and reduces lipid
      storage and plaque formation in ApoE-/- mice fed a high-fat diet, with no obvious
      long-term toxicity. Together, this suggests CuS-TRPV1 may represent a therapeutic
      tool to locally and temporally attenuate atherosclerosis.

PMID- 29335451
TI  - A hot-spot mutation in CDC42 (p.Tyr64Cys) and novel phenotypes in the third
      patient with Takenouchi-Kosaki syndrome.
AB  - Takenouchi-Kosaki syndrome (TKS) is a congenital malformation syndrome
      characterized by severe developmental delay, macrothrombocytopenia,
      camptodactyly, sensorineural hearing loss, and dysmorphic facial features.
      Recently, a heterozygous de novo mutation (p.Tyr64Cys) in the CDC42 gene, which
      encodes a key small GTP-binding protein of the Rho-subfamily, was identified in
      two unrelated patients with TKS. We herein report a third patient with TKS who
      had the same heterozygous CDC42 mutation. The phenotype of the patient was very
      similar to those of the two previously reported patients with TKS; however, she
      also demonstrated novel clinical manifestations, such as congenital
      hypothyroidism and immunological disturbance. Thus, despite the heterozygous
      mutation of CDC42 (p.Tyr64Cys) likely being a hot-spot mutation for TKS, its
      phenotype may be variable. Further studies and the accumulation of patients with
      CDC42 mutations are needed to clarify the phenotype in patients with TKS and the
      pathophysiological roles of the CDC42 mutation.

PMID- 29335453
TI  - Engineering Yarrowia lipolytica to Simultaneously Produce Lipase and Single Cell
      Protein from Agro-industrial Wastes for Feed.
AB  - Lipases are scarcely exploited as feed enzymes in hydrolysis of lipids for
      increasing energy supply and improving nutrient use efficiency. In this work, we
      performed homologous overexpression, in vitro characterization and in vivo
      assessment of a lipase from the yeast Yarrowia lipolytica for feed purpose.
      Simultaneously, a large amount of yeast cell biomass was produced, for use as
      single cell protein, a potential protein-rich feed resource. Three kinds of low
      cost agro-industrial wastes were tested as substrates for simultaneous production
      of lipase and single cell protein (SCP) as feed additives: sugarcane molasses,
      waste cooking oil and crude glycerol from biodiesel production. Sugarcane
      molasses appeared as the most effective cheap medium, allowing production of
      16420 U/ml of lipase and 151.2 g/L of single cell protein at 10 liter
      fermentation scale. In vitro characterization by mimicking a gastro-intestinal
      environment and determination of essential amino acids of the SCP, and in vivo
      oral feeding test on fish all revealed that lipase, SCP and their combination
      were excellent feed additives. Such simultaneous production of this lipase and
      SCP could address two main concerns of feed industry, poor utilization of lipid
      and shortage of protein resource at the same time.

PMID- 29335455
TI  - Publisher Correction: Trapping and manipulation of nanoparticles using multifocal
      optical vortex metalens.
AB  - A correction to this article has been published and is linked from the HTML
      version of this paper. The error has been fixed in the paper.

PMID- 29335454
TI  - Relationship between spectrotemporal modulation detection and music perception in
      normal-hearing, hearing-impaired, and cochlear implant listeners.
AB  - The objective of this study was to examine the relationship between
      spectrotemporal modulation (STM) sensitivity and the ability to perceive music.
      Ten normal-nearing (NH) listeners, ten hearing aid (HA) users with moderate
      hearing loss, and ten cochlear Implant (CI) users participated in this study.
      Three different types of psychoacoustic tests including spectral modulation
      detection (SMD), temporal modulation detection (TMD), and STM were administered.
      Performances on these psychoacoustic tests were compared to music perception
      abilities. In addition, psychoacoustic mechanisms involved in the improvement of
      music perception through HA were evaluated. Music perception abilities in unaided
      and aided conditions were measured for HA users. After that, HA benefit for music
      perception was correlated with aided psychoacoustic performance. STM detection
      study showed that a combination of spectral and temporal modulation cues were
      more strongly correlated with music perception abilities than spectral or
      temporal modulation cues measured separately. No correlation was found between
      music perception performance and SMD threshold or TMD threshold in each group.
      Also, HA benefits for melody and timbre identification were significantly
      correlated with a combination of spectral and temporal envelope cues though HA.

PMID- 29335456
TI  - Incidence of solid tumors in polycythemia vera treated with phlebotomy with or
      without hydroxyurea: ECLAP follow-up data.

PMID- 29335457
TI  - An equation-of-state-meter of quantum chromodynamics transition from deep
      learning.
AB  - A primordial state of matter consisting of free quarks and gluons that existed in
      the early universe a few microseconds after the Big Bang is also expected to form
      in high-energy heavy-ion collisions. Determining the equation of state (EoS) of
      such a primordial matter is the ultimate goal of high-energy heavy-ion
      experiments. Here we use supervised learning with a deep convolutional neural
      network to identify the EoS employed in the relativistic hydrodynamic simulations
      of heavy ion collisions. High-level correlations of particle spectra in
      transverse momentum and azimuthal angle learned by the network act as an
      effective EoS-meter in deciphering the nature of the phase transition in quantum
      chromodynamics. Such EoS-meter is model-independent and insensitive to other
      simulation inputs including the initial conditions for hydrodynamic simulations.

PMID- 29335458
TI  - Publisher Correction: Microbial network of the carbonate precipitation process
      induced by microbial consortia and the potential application to crack healing in
      concrete.
AB  - A correction to this article has been published and is linked from the HTML
      version of this paper. The error has been fixed in the paper.

PMID- 29335459
TI  - Publisher Correction: Discovery of targetable genetic alterations in advanced non
      small cell lung cancer using a next-generation sequencing-based circulating tumor
      DNA assay.
AB  - A correction to this article has been published and is linked from the HTML
      version of this paper. The error has been fixed in the paper.

PMID- 29335460
TI  - God is watching: history in the age of near-infinite digital archives.

PMID- 29335461
TI  - Pixelated spatial gene expression analysis from tissue.
AB  - Here, we present a technique that performs on-chip picoliter real-time reverse
      transcriptase loop mediated isothermal amplification (RT-LAMP) reactions on a
      histological tissue section without any analyte purification while preserving the
      native spatial location of the nucleic acid molecules. We demonstrate this method
      by amplifying TOP2A messenger RNA (mRNA) in a prostate cancer xenograft with 100
      um spatial resolution and by visualizing the variation in threshold time of
      amplification across the tissue. The on-chip reaction was validated by mRNA
      fluorescence in situ hybridization (mFISH) from cells in the tissue section. The
      entire process, from tissue loading on microchip to results from RT-LAMP can be
      carried out in less than 2 h. We anticipate that this technique, with its ease of
      use, fast turnaround, and quantitative molecular outputs, would become an
      invaluable tissue analysis tool for researchers and clinicians in the biomedical
      arena.

PMID- 29335462
TI  - Iron-related toxicity of single-walled carbon nanotubes and crocidolite fibres in
      human mesothelial cells investigated by Synchrotron XRF microscopy.
AB  - Carbon nanotubes (CNTs) are promising products in industry and medicine, but
      there are several human health concerns since their fibrous structure resembles
      asbestos. The presence of transition metals, mainly iron, in the fibres seems
      also implicated in the pathogenetic mechanisms. To unravel the role of iron at
      mesothelial level, we compared the chemical changes induced in MeT-5A cells by
      the exposure to asbestos (crocidolite) or CNTs at different content of iron
      impurities (raw-SWCNTs, purified- and highly purified-SWCNTs). We applied
      synchrotron-based X-Ray Fluorescence (XRF) microscopy and soft X-ray imaging
      (absorption and phase contrast images) to monitor chemical and morphological
      changes of the exposed cells. In parallel, we performed a ferritin assay. X-ray
      microscopy imaging and XRF well localize the crocidolite fibres interacting with
      cells, as well as the damage-related morphological changes. Differently, CNTs
      presence could be only partially evinced by low energy XRF through carbon
      distribution and sometimes iron co-localisation. Compared to controls, the cells
      treated with raw-SWCNTs and crocidolite fibres showed a severe alteration of iron
      distribution and content, with concomitant stimulation of ferritin production.
      Interestingly, highly purified nanotubes did not altered iron metabolism. The
      data provide new insights for possible CNTs effects at mesothelial/pleural level
      in humans.

PMID- 29335463
TI  - Sub-kb Hi-C in D. melanogaster reveals conserved characteristics of TADs between
      insect and mammalian cells.
AB  - Topologically associating domains (TADs) are fundamental elements of the
      eukaryotic genomic structure. However, recent studies suggest that the insulating
      complexes, CTCF/cohesin, present at TAD borders in mammals are absent from those
      in Drosophila melanogaster, raising the possibility that border elements are not
      conserved among metazoans. Using in situ Hi-C with sub-kb resolution, here we
      show that the D. melanogaster genome is almost completely partitioned into >4000
      TADs, nearly sevenfold more than previously identified. The overwhelming majority
      of these TADs are demarcated by the insulator complexes, BEAF-32/CP190, or BEAF
      32/Chromator, indicating that these proteins may play an analogous role in flies
      as that of CTCF/cohesin in mammals. Moreover, extended regions previously thought
      to be unstructured are shown to consist of small contiguous TADs, a property also
      observed in mammals upon re-examination. Altogether, our work demonstrates that
      fundamental features associated with the higher-order folding of the genome are
      conserved from insects to mammals.

PMID- 29335464
TI  - Evaluation of endothelial function by VOP and inflammatory biomarkers in patients
      with arterial hypertension.
AB  - Hypertension is associated with microcirculatory impairment. Our objectives were
      to evaluate endothelial function and inflammatory biomarkers in patients with
      resistant (RH) and mild to moderate (MMH) arterial hypertension in comparison to
      normotensives (control group-CG). Three groups, 25 patients each, have been
      investigated, by anamnesis, venous occlusion plethysmography (VOP) and serum
      determination of adhesion molecules (VCAM, ICAM), adiponectin, endothelin and C
      reactive protein (CRP). Patients not using statins and with or without blood
      pressure control were also analyzed. RH group showed smaller percentage increase
      of maximum forearm blood flow (FBF) (endothelial-dependent vasodilatation) than
      controls (p < 0.05), but no significant difference could be detected between MMH
      and CG groups on maximum FBF and minimum vascular resistance post-ischemia. RH
      and MMH groups showed higher resistance averages compared to controls (p < 0.05).
      Uncontrolled BP in hypertensive patients showed worse results for blood flow and
      resistance. Endothelial-independent vasodilatation was not affected. Endothelin
      levels were higher in RH and MMH groups (p < 0.05) not using statins. CRP was
      significantly higher only in RH compared to CG (p < 0.05). In conclusion patients
      with severe hypertension and lack of blood pressure control showed greater
      impairment of endothelial function with higher CRP and endothelin levels.

PMID- 29335465
TI  - The high concentration of progesterone is harmful for endometrial receptivity and
      decidualization.
AB  - Progesterone is required for the establishment and maintenance of mammalian
      pregnancy and widely used for conservative treatment of luteal phase deficiency
      in clinics. However, there are limited solid evidences available for the optimal
      timing and dose of progesterone therapy, especially for the possible adverse
      effects on implantation and decidualization when progesterone is administrated
      empirically. In our study, mouse models were used to examine effects of excess
      progesterone on embryo implantation and decidualization. Our data indicate that
      excess progesterone is not only harmful for mouse implantation, but also impairs
      mouse decidualization. In excess progesterone-treated mice, the impaired
      LIF/STAT3 pathway and dysregulated endoplasmic reticulum stress may lead to the
      inhibition of embryo implantation and decidualization. It is possible that the
      decrease in birth weight of excess progesterone-treated mice is due to a
      compromised embryo implantation and decidualization. Furthermore, excess
      progesterone compromises in vitro decidualization of human endometrial stromal
      cells.

PMID- 29335466
TI  - Deeply-sourced formate fuels sulfate reducers but not methanogens at Lost City
      hydrothermal field.
AB  - Hydrogen produced during water-rock serpentinization reactions can drive the
      synthesis of organic compounds both biotically and abiotically. We investigated
      abiotic carbon production and microbial metabolic pathways at the high energy but
      low diversity serpentinite-hosted Lost City hydrothermal field. Compound-specific
      14C data demonstrates that formate is mantle-derived and abiotic in some
      locations and has an additional, seawater-derived component in others. Lipids
      produced by the dominant member of the archaeal community, the Lost City
      Methanosarcinales, largely lack 14C, but metagenomic evidence suggests they
      cannot use formate for methanogenesis. Instead, sulfate-reducing bacteria may be
      the primary consumers of formate in Lost City chimneys. Paradoxically, the
      archaeal phylotype that numerically dominates the chimney microbial communities
      appears ill suited to live in pure hydrothermal fluids without the co-occurrence
      of organisms that can liberate CO2. Considering the lack of dissolved inorganic
      carbon in such systems, the ability to utilize formate may be a key trait for
      survival in pristine serpentinite-hosted environments.

PMID- 29335467
TI  - An engineered CARS substrate with giant field enhancement in crisscross dimer
      nanostructure.
AB  - We theoretically investigate the optical properties of a nanostructure consisting
      of the two identical and symmetrically arranged crisscrosses. A plasmonic Fano
      resonance is induced by a strong interplay between bright mode and dark modes,
      where the bright mode is due to electric dipole resonance while dark modes
      originate from the magnetic dipole induced by LC resonances. In this article, we
      find that the electric field "hotspots" corresponding to three different
      wavelengths can be positioned at the same spatial position, and its spectral
      tunability is achieved by changing geometric parameters. The crisscrosses system
      can be designed as a plasmonic substrate for enhancing Coherent Anti-Stokes Raman
      Scattering (CARS) signal. This discovery provides a new method to achieve single
      molecule detection. At the same time, it also has many important applications for
      multi-photon imaging and other nonlinear optical processes, such as four-wave
      mixing and stimulated Raman scattering.

PMID- 29335468
TI  - AICDA drives epigenetic heterogeneity and accelerates germinal center-derived
      lymphomagenesis.
AB  - Epigenetic heterogeneity is emerging as a feature of tumors. In diffuse large B
      cell lymphoma (DLBCL), increased cytosine methylation heterogeneity is associated
      with poor clinical outcome, yet the underlying mechanisms remain unclear.
      Activation-induced cytidine deaminase (AICDA), an enzyme that mediates affinity
      maturation and facilitates DNA demethylation in germinal center (GC) B cells, is
      required for DLBCL pathogenesis and linked to inferior outcome. Here we show that
      AICDA overexpression causes more aggressive disease in BCL2-driven murine
      lymphomas. This phenotype is associated with increased cytosine methylation
      heterogeneity, but not with increased AICDA-mediated somatic mutation burden.
      Reciprocally, the cytosine methylation heterogeneity characteristic of normal GC
      B cells is lost upon AICDA depletion. These observations are relevant to human
      patients, since DLBCLs with high AICDA expression manifest increased methylation
      heterogeneity vs. AICDA-low DLBCLs. Our results identify AICDA as a driver of
      epigenetic heterogeneity in B-cell lymphomas with potential significance for
      other tumors with aberrant expression of cytidine deaminases.

PMID- 29335469
TI  - Structural basis for chitin acquisition by marine Vibrio species.
AB  - Chitin, an insoluble polymer of N-acetylglucosamine, is one of the most abundant
      biopolymers on Earth. By degrading chitin, chitinolytic bacteria such as Vibrio
      harveyi are critical for chitin recycling and maintenance of carbon and nitrogen
      cycles in the world's oceans. A decisive step in chitin degradation is the uptake
      of chito-oligosaccharides by an outer membrane protein channel named chitoporin
      (ChiP). Here, we report X-ray crystal structures of ChiP from V. harveyi in the
      presence and absence of chito-oligosaccharides. Structures without bound sugar
      reveal a trimeric assembly with an unprecedented closing of the transport pore by
      the N-terminus of a neighboring subunit. Substrate binding ejects the pore plug
      to open the transport channel. Together with molecular dynamics simulations,
      electrophysiology and in vitro transport assays our data provide an explanation
      for the exceptional affinity of ChiP for chito-oligosaccharides and point to an
      important role of the N-terminal gate in substrate transport.

PMID- 29335470
TI  - Stratospheric ozone loss over the Eurasian continent induced by the polar vortex
      shift.
AB  - The Montreal Protocol has succeeded in limiting major ozone-depleting substance
      emissions, and consequently stratospheric ozone concentrations are expected to
      recover this century. However, there is a large uncertainty in the rate of
      regional ozone recovery in the Northern Hemisphere. Here we identify a Eurasia
      North America dipole mode in the total column ozone over the Northern Hemisphere,
      showing negative and positive total column ozone anomaly centres over Eurasia and
      North America, respectively. The positive trend of this mode explains an enhanced
      total column ozone decline over the Eurasian continent in the past three decades,
      which is closely related to the polar vortex shift towards Eurasia. Multiple
      chemistry-climate-model simulations indicate that the positive Eurasia-North
      America dipole trend in late winter is likely to continue in the near future. Our
      findings suggest that the anticipated ozone recovery in late winter will be
      sensitive not only to the ozone-depleting substance decline but also to the polar
      vortex changes, and could be substantially delayed in some regions of the
      Northern Hemisphere extratropics.

PMID- 29335471
TI  - Raman enhancement on ultra-clean graphene quantum dots produced by quasi
      equilibrium plasma-enhanced chemical vapor deposition.
AB  - Graphene is regarded as a potential surface-enhanced Raman spectroscopy (SERS)
      substrate. However, the application of graphene quantum dots (GQDs) has had
      limited success due to material quality. Here, we develop a quasi-equilibrium
      plasma-enhanced chemical vapor deposition method to produce high-quality ultra
      clean GQDs with sizes down to 2 nm directly on SiO2/Si, which are used as SERS
      substrates. The enhancement factor, which depends on the GQD size, is higher than
      conventional graphene sheets with sensitivity down to 1 * 10-9 mol L-1 rhodamine.
      This is attributed to the high-quality GQDs with atomically clean surfaces and
      large number of edges, as well as the enhanced charge transfer between molecules
      and GQDs with appropriate diameters due to the existence of Van Hove
      singularities in the electronic density of states. This work demonstrates a
      sensitive SERS substrate, and is valuable for applications of GQDs in graphene
      based photonics and optoelectronics.

PMID- 29335472
TI  - Provided support, caregiver burden and well-being in partners of persons with
      spinal cord injury 5 years after discharge from first inpatient rehabilitation.
AB  - STUDY DESIGN: Cross-sectional study. OBJECTIVES: To describe type and regularity
      of support given by partners for individuals with paraplegia versus tetraplegia 5
      years after discharge from first inpatient rehabilitation; to describe perceived
      caregiver burden, mental health and life satisfaction among partners; and to
      analyse determinants of perceived burden and the partner's mental health and life
      satisfaction. SETTING: The Netherlands. METHODS: Participants were partners of
      persons with spinal cord injury (SCI) 5 years after discharge from first
      inpatient rehabilitation (N = 67). Participants completed a self-report
      questionnaire. Provided support was assessed with an existing scale consisting of
      25 activities for which partners could indicate how often they provide support to
      the patient. Caregiver burden was assessed with the Caregiver Strain Index.
      Mental health was measured with the Short-Form Health Survey 36 (mental health
      subscale), and life satisfaction was measured with the Life Satisfaction
      Questionnaire. RESULTS: Five years after inpatient rehabilitation, partners
      provided support with a large variety of activities. How often and in which
      activities partners provided support was associated with lesion level. About 43%
      of the partners experienced high levels of caregiver burden. Provided support was
      related to perceived burden (rS = 0.58) and life satisfaction (rS = -0.24), and
      burden was negatively related to mental health (rS = -0.47) and life satisfaction
      (rS = -0.67). CONCLUSIONS: High levels of perceived burden among partners and the
      associations between higher burden with lower well-being show the importance to
      prevent caregiver overload in partners of individuals with SCI. Monitoring burden
      during regular rehabilitation visits may help to early detect burden.

PMID- 29335473
TI  - Mental health and life satisfaction of individuals with spinal cord injury and
      their partners 5 years after discharge from first inpatient rehabilitation.
AB  - STUDY DESIGN: Cross-sectional study. OBJECTIVES: To describe and compare mental
      health and life satisfaction between individuals with spinal cord injury (SCI)
      and their partners 5 years after discharge from first inpatient rehabilitation;
      and to examine if injury severity moderates the association between individuals'
      with SCI and their partners' mental health and life satisfaction. SETTING: Dutch
      community. METHODS: Sixty-five individuals with SCI and their partners completed
      a self-report questionnaire. Main outcome measures were the mental health
      subscale of the Short-Form Health Survey and the Life Satisfaction Questionnaire.
      RESULTS: Levels of mental health and life satisfaction of individuals with SCI
      and partners were similar, with median scores of 76 and 4.8 versus 76 and 4.6,
      respectively. Moderate to strong correlations between individuals with SCI and
      their partners were found for the mental health (rS = 0.35) and life satisfaction
      scores (rS = 0.51). These associations were generally stronger in the subgroup of
      individuals with less severe SCI. Associations between scores on separate life
      domains ranged from negligible (0.05) to moderate (0.53). Individuals with SCI
      and their partners were least satisfied with their 'sexual life'. Compared with
      their partners, individuals with SCI were significantly more satisfied in the
      domains 'leisure situation', 'partnership relation' and 'family life', and less
      satisfied in 'self-care ability'. CONCLUSIONS: This study showed similarities but
      also differences in mental health and life satisfaction between individuals with
      SCI and their partners. In clinical practice, attention on mental health and life
      satisfaction should, therefore, focus on different domains for individuals with
      SCI and partners.

PMID- 29335474
TI  - Low vitamin D levels are independent predictors of 1-year worsening in physical
      function in people with chronic spinal cord injury: a longitudinal study.
AB  - STUDY DESIGN: Longitudinal cohort study. OBJECTIVE: To explore the longitudinal
      association of baseline vitamin D levels with 1-year change in physical function
      outcomes in people with chronic spinal cord injury (SCI). SETTING: Rehabilitation
      institute. METHODS: Sixty-seven patients (44 men and 23 women) with chronic SCI
      admitted to a rehabilitation program were included. Functional independence in
      daily living activities (as evaluated by the Spinal Cord Independence Measure
      version III, SCIM III) and leisure time physical activity (LTPA) were assessed as
      measures of physical function at the admission and re-assessed 1-year later.
      Comorbidity was scored by Charlson comorbidity index (CCI). RESULTS: A 1-year
      worsening in SCIM and LTPA were registered in 44 and 40 patients (66% and 60% of
      the study population), respectively. They exhibited significantly lower baseline
      25(OH)D levels, higher CCI, and shorter distance from the injury. At the multiple
      linear regression analyses, lower baseline 25(OH)D levels exhibited a significant
      independent association with higher percentages of 1-year worsening in both SCIM
      and LTPA. At ROC analysis, baseline 25(OH)D levels <18.6 and <18.2 ng/mL
      discriminated individuals with 1-year worsening in SCIM and LTPA, respectively.
      According to these cut-off points, at the multiple logistic regression analysis,
      patients with low baseline 25(OH)D levels exhibited an OR of worsening in SCIM
      and LTPA engagement 2.8- and 2.6-fold higher, after adjustment for CCI, distance
      from injury, and post-follow-up 25(OH)D levels. CONCLUSIONS: In people with
      chronic SCI, a low 25(OH)D level may represent an independent predictor of
      worsening in physical function outcomes over time.

PMID- 29335475
TI  - Discontinuous ventilator weaning of patients with acute SCI.
AB  - STUDY DESIGN: Retrospective, single centre cohort study. OBJECTIVES: To determine
      factors associated with ventilator weaning success and failure in patients with
      acute spinal cord injury (SCI); determine length of time and attempts required to
      wean from the ventilator successfully and determine the incidence of pneumonia.
      SETTING: BG Klinikum Hamburg, Level 1 trauma centre, SCI Department, Germany.
      METHODS: From 2010 until 2017, 165 consecutive patients with cervical SCI,
      initially dependent on a ventilator, were included and weaned discontinuously via
      tracheal cannula. Data related to anthropometric details, neurological injury,
      respiratory outcomes, and weaning parameters were prospectively recorded in a
      database and retrospectively analysed. RESULTS: Seventy-nine percent of all
      patients were successfully weaned from ventilation. Average duration of the
      complete weaning process was 37 days. Ninety-one percent of the successfully
      weaned patients completed this on first attempt. Age (>56 years), level of injury
      (C4 and/or above), vital capacity (<1500 ml), obesity (>25 kg/m2), and chronic
      obstructive pulmonary disease (COPD) significantly decreased the chance of
      successful weaning. These factors also correlated with a higher number of weaning
      attempts. High level of injury, older age, and reduced vital capacity also
      increased the duration of the weaning process. Patients with low vital capacity
      and concurrent therapy with Baclofen and Dantrolene showed higher rates of
      pneumonia. CONCLUSIONS: We conclude that mentioned factors are associated with
      weaning outcome and useful for clinical recommendations and patient counselling.
      These data further support the complexity of ventilator weaning in the SCI
      population due to associated complications, therefore we recommend conducting
      weaning of patients with SCI on intensive or intermediate care units (ICU/IMCU)
      in specialised centres.

PMID- 29335476
TI  - Reliability and validity of the Persian version of the spinal cord injury
      lifestyle scale and the health behavior questionnaire in persons with spinal cord
      injury.
AB  - STUDY DESIGN: Cross-sectional psychometric study. OBJECTIVE: To evaluate the
      reliability and validity of a spinal cord injury lifestyle scale (SCILS) and
      Health Behavior Questionnaire (HBQ) in the Persian language for persons with
      spinal cord injury (SCI). SETTING: Participants were selected among those
      referred to health centers and the Brain and Spinal Cord Injury Research Center.
      METHOD: In accordance with standard procedure for translation, two
      questionnaires, the SCILS and HBQ, were translated using a forward and backward
      translation approach by professional translators. Face validity of the
      questionnaires was assessed by ten persons with SCI and content validity was
      agreed upon by 12 professors from health care teaching universities. To test the
      final versions of both questionnaires, 97 persons with SCI were included using a
      consecutive sampling method. Other questionnaires were used to assess concurrent
      validity (secondary impairment checklist, as well as SCILS and HBQ) and
      convergent validity (impact of event scale revised, brief symptom inventory, beck
      depression inventory, and functional independence measure). RESULTS: Internal
      consistency of SCILS and HBQ, assessed by Cronbach's alpha, was 0.75 for SCILS
      and 0.85 for HBQ. Test-retest reliability intraclass correlations were 0.86 and
      0.92 for SCILS and HBQ, respectively. The number of current secondary impairments
      had a significant and negative correlation with SCILS (r = -0.22, P < 0.001), but
      it was not correlated with HBQ. SCILS had a significant and strong correlation
      with HBQ (r = 0.65, P < 0.001). CONCLUSION: SCILS and HBQ can be used for
      measuring the health behavior of persons with SCI in Iran.

PMID- 29335478
TI  - Publisher Correction: Marked bias towards spontaneous synaptic inhibition
      distinguishes non-adapting from adapting layer 5 pyramidal neurons in the barrel
      cortex.
AB  - A correction to this article has been published and is linked from the HTML
      version of this paper. The error has been fixed in the paper.

PMID- 29335477
TI  - Transcriptomic signatures of cellular and humoral immune responses in older
      adults after seasonal influenza vaccination identified by data-driven clustering.
AB  - PBMC transcriptomes after influenza vaccination contain valuable information
      about factors affecting vaccine responses. However, distilling meaningful
      knowledge out of these complex datasets is often difficult and requires advanced
      data mining algorithms. We investigated the use of the data-driven Weighted Gene
      Correlation Network Analysis (WGCNA) gene clustering method to identify vaccine
      response-related genes in PBMC transcriptomic datasets collected from 138 healthy
      older adults (ages 50-74) before and after 2010-2011 seasonal trivalent influenza
      vaccination. WGCNA separated the 14,197 gene dataset into 15 gene clusters based
      on observed gene expression patterns across subjects. Eight clusters were
      strongly enriched for genes involved in specific immune cell types and processes,
      including B cells, T cells, monocytes, platelets, NK cells, cytotoxic T cells,
      and antiviral signaling. Examination of gene cluster membership identified
      signatures of cellular and humoral responses to seasonal influenza vaccination,
      as well as pre-existing cellular immunity. The results of this study illustrate
      the utility of this publically available analysis methodology and highlight genes
      previously associated with influenza vaccine responses (e.g., CAMK4, CD19), genes
      with functions not previously identified in vaccine responses (e.g., SPON2, MATK,
      CST7), and previously uncharacterized genes (e.g. CORO1C, C8orf83) likely related
      to influenza vaccine-induced immunity due to their expression patterns.

PMID- 29335479
TI  - LPS-induced Vitamin D Receptor Decrease in Oral Keratinocytes Is Associated With
      Oral Lichen Planus.
AB  - The suppressive function of vitamin D on oral lichen planus (OLP) have been
      documented previously. Vitamin D receptor (VDR) expression is down-regulated in
      OLP, but the molecular mechanism of its decrease and the related anti
      inflammatory contributor of epithelial VDR signaling is unclear. Herein, we
      demonstrated that lipopolysaccharide (LPS) remarkedly down-regulated VDR
      expression of keratinocytes, and the reduced regulation was dependent on tumor
      necrosis factor alpha (TNFalpha)-miR-346 pathway. In human specimen studies, VDR
      levels of oral mucosal epithelia from OLP patients decreased substantially
      accompanied with robust TNFalpha and miR-346 induction, compared to the normal
      tissues. In addition, vitamin D/VDR signaling inhibited LPS-induced p53
      upregulated modulator of apoptosis (PUMA) induction in keratinocytes via impeding
      nuclear factor-kappaB (NF-kappaB) activation, resulting in keratinocytes
      apoptosis reduction. Importantly, PUMA activity was up-regulated strongly in
      diseased epithelium, reversely correlated with VDR expression. Totally, our data
      indicate that LPS is responsible for VDR downregulation in oral keratinocytes,
      which is associated with OLP development.

PMID- 29335482
TI  - Engineered nonlinear materials using gold nanoantenna array.
AB  - Gold dipole nanoantennas embedded in an organic molecular film provide strong
      local electromagnetic fields to enhance both the nonlinear refractive index (n2)
      and two-photon absorption (2PA) of the molecules. An enhancement of 53* for 2PA
      and 140* for nonlinear refraction is observed for BDPAS (4,4'
      bis(diphenylamino)stilbene) at 600 nm with only 3.7% of gold volume fraction. The
      complex value of the third-order susceptibility enhancement results in a sign
      change of n2 for the effective composite material relative to the pure BDPAS
      film. This complex nature of the enhancement and the tunability of the
      nanoantenna resonance allow for engineering the effective nonlinear response of
      the composite film.

PMID- 29335481
TI  - Bioimpedimetric analysis in conjunction with growth dynamics to differentiate
      aggressiveness of cancer cells.
AB  - Determination of cancer aggressiveness is mainly assessed in tissues by looking
      at the grade of cancer. There is a lack of specific method to determine
      aggressiveness of cancer cells in vitro. In our present work, we have proposed a
      bio-impedance based non-invasive method to differentiate aggressive property of
      two breast cancer cell lines. Real-time impedance analysis of MCF-7 (less
      aggressive) and MDA-MB-231 cells (more aggressive) demonstrated unique growth
      pattern. Detailed slope-analysis of impedance curves at different growth phases
      showed that MDA-MB-231 had higher proliferation rate and intrinsic resistance to
      cell death, when allowed to grow in nutrient and space limiting conditions. This
      intrinsic nature of death resistance of MDA-MB-231 was due to modulation and
      elongation of filopodia, which was also observed during scanning electron
      microscopy. Results were also similar when validated by cell cycle analysis.
      Additionally, wavelet based analysis was used to demonstrate that MCF-7 had
      lesser micromotion based cellular activity, when compared with MDA-MB-231.
      Combined together, we hypothesize that analysis of growth rate, death resistance
      and cellular energy, through bioimpedance based analysis can be used to determine
      and compare aggressiveness of multiple cancer cell lines. This further opens
      avenues for extrapolation of present work to human tumor tissue samples.

PMID- 29335480
TI  - Novel analgesic effects of melanin-concentrating hormone on persistent
      neuropathic and inflammatory pain in mice.
AB  - The melanin-concentrating hormone (MCH) is a peptidergic neuromodulator
      synthesized by neurons in the lateral hypothalamus and zona incerta. MCHergic
      neurons project throughout the central nervous system, indicating the
      involvements of many physiological functions, but the role in pain has yet to be
      determined. In this study, we found that pMCH-/- mice showed lower baseline pain
      thresholds to mechanical and thermal stimuli than did pMCH+/+ mice, and the time
      to reach the maximum hyperalgesic response was also significantly earlier in both
      inflammatory and neuropathic pain. To examine its pharmacological properties, MCH
      was administered intranasally into mice, and results indicated that MCH treatment
      significantly increased mechanical and thermal pain thresholds in both pain
      models. Antagonist challenges with naltrexone (opioid receptor antagonist) and
      AM251 (cannabinoid 1 receptor antagonist) reversed the analgesic effects of MCH
      in both pain models, suggesting the involvement of opioid and cannabinoid
      systems. MCH treatment also increased the expression and activation of CB1R in
      the medial prefrontal cortex and dorsolateral- and ventrolateral periaqueductal
      grey. The MCH1R antagonist abolished the effects induced by MCH. This is the
      first study to suggest novel analgesic actions of MCH, which holds great promise
      for the application of MCH in the therapy of pain-related diseases.

PMID- 29335483
TI  - Pilot study to assess visualization and therapy of inflammatory mechanisms after
      vessel reopening in a mouse stroke model.
AB  - After reperfusion therapy in stroke patients secondary inflammatory processes may
      increase cerebral damage. In this pilot study, effects of anti-inflammatory
      therapy were assessed in a middle cerebral artery occlusion (MCAO) mouse model
      after reperfusion. 1 hour after MCAO, the artery was reopened and tacrolimus or
      NaCl were administered intra-arterially. Perfusion-weighted (PWI) and diffusion
      weighted images (DWI) were obtained by MRI during MCAO. DWI, T2- and T1-weighted
      images with and without Bis-5HT-DTPA administration were obtained 24 hours after
      MCAO. Neutrophils, Myeloperoxidase-positive-(MPO+)-cells and microglia, including
      M1 and M2 phenotypes, were assessed immunohistochemically. Treatment with
      tacrolimus led to significantly smaller apparent diffusion coefficient (ADC)
      lesion volume within 24 hours (median -55.6mm3, range -81.3 to -3.6, vs. median
      8.0 mm3, range 1.2 to 41.0; P = 0.008) and significantly lower enhancement of Bis
      5-HT-DTPA (median signal intensity (SI) ratiocortex, median 92.0%, range 82.8% to
      97.1%, vs. median 103.1%, range 98.7% to 104.6%; P = 0.008) compared to the NaCl
      group. Immunohistochemical analysis showed no significant differences between
      both groups. Intra-arterially administered anti-inflammatory agents after
      mechanical thrombectomy may improve treatment efficiency in stroke by reducing
      infarct volume size and MPO activity.

PMID- 29335484
TI  - Microbial Competition of Rhodotorula mucilaginosa UANL-001L and E. coli increase
      biosynthesis of Non-Toxic Exopolysaccharide with Applications as a Wide-Spectrum
      Antimicrobial.
AB  - Bacterial species are able to colonize and establish communities in biotic and
      abiotic surfaces. Moreover, within the past five decades, incidence of bacterial
      strains resistant to currently used antibiotics has increased dramatically. This
      has led to diverse health issues and economical losses for different industries.
      Therefore, there is a latent need to develop new and more efficient
      antimicrobials. This work reports an increased production of an exopolysaccharide
      in a native yeast strain isolated from the Mexican Northeast, Rhodotorula
      mucilaginosa UANL-001L, when co-cultured with E. coli. The exopolysaccharide
      produced is chemically and physically characterized and its applications as an
      antimicrobial and antibiofilm are explored. The exopolysaccharide is capable of
      inhibiting planktonic growth and biofilm formation in Escherichia coli,
      Pseudomonas aeruginosa and Staphylococcus aureus. Additionally, the
      exopolysaccharide studied here does not exhibit cytotoxic effects when assessed
      both, in vitro against an H9c2 mammalian cell line, and in vivo in a murine
      toxicity model. Taken together, the properties of this exopolysaccharide indicate
      that it has potential applications to inhibit bacterial colonization in medical
      and industrial settlings.

PMID- 29335485
TI  - Electron beam melting in the fabrication of three-dimensional mesh titanium
      mandibular prosthesis scaffold.
AB  - The study was designed to fulfill effective work-flow to fabricate three
      dimensional mesh titanium scaffold for mandibular reconstruction. The 3D titanium
      mesh scaffold was designed based on a volunteer with whole mandible defect. (1)
      acquisition of the CT data; (2) design with computer aided design (CAD) and
      finite element analysis (FEA). The pore size and intervals with the best mechanic
      strength was also calculated using FEA. (3) fabrication of the scaffold using
      electron beam melting (EBM); (4) implantation surgery. The case recovered well,
      without loosening and rejection. Additionally, 12 mandibular defect model beagles
      were used to verify the results. The model was established via tooth extraction
      and mandibular resection surgeries, and the scaffold was designed individually
      based on CT data obtained at 2 weeks after extraction operation. Then scaffolds
      were fabricated using 3D EBM, and the implantation surgery was performed at 2
      months after extraction operation. All the animals healed well after
      implantation, and the grafted mandibular recovered well with time. The relevant
      parameters of the grafted mandibular were nearly to the native mandibular at
      postoperative 12 months. It is feasible to fabricate mesh titanium scaffold for
      repairing mandibular defects individually using reverse engineering, CAD and EBM
      techniques.

PMID- 29335486
TI  - High-resolution TADs reveal DNA sequences underlying genome organization in
      flies.
AB  - Despite an abundance of new studies about topologically associating domains
      (TADs), the role of genetic information in TAD formation is still not fully
      understood. Here we use our software, HiCExplorer (hicexplorer.readthedocs.io) to
      annotate >2800 high-resolution (570 bp) TAD boundaries in Drosophila
      melanogaster. We identify eight DNA motifs enriched at boundaries, including a
      motif bound by the M1BP protein, and two new boundary motifs. In contrast to
      mammals, the CTCF motif is only enriched on a small fraction of boundaries
      flanking inactive chromatin while most active boundaries contain the motifs bound
      by the M1BP or Beaf-32 proteins. We demonstrate that boundaries can be accurately
      predicted using only the motif sequences at open chromatin sites. We propose that
      DNA sequence guides the genome architecture by allocation of boundary proteins in
      the genome. Finally, we present an interactive online database to access and
      explore the spatial organization of fly, mouse and human genomes, available at
      http://chorogenome.ie-freiburg.mpg.de .

PMID- 29335487
TI  - Increased Expression of GLP-1R in Proliferating Islets of Men1 Mice is Detectable
      by [68Ga]Ga-DO3A-VS-Cys40-Exendin-4 /PET.
AB  - Multiple endocrine neoplasia type 1 (MEN1) is an endocrine tumor syndrome caused
      by heterozygous mutations in the MEN1 tumor suppressor gene. The MEN1 pancreas of
      the adolescent gene carrier frequently contain diffusely spread pre-neoplasias
      and microadenomas, progressing to macroscopic and potentially malignant
      pancreatic neuroendocrine tumors (P-NET), which represents the major death cause
      in MEN1. The unveiling of the molecular mechanism of P-NET which is not currently
      understood fully to allow the optimization of diagnostics and treatment. Glucagon
      like peptide 1 (GLP-1) pathway is essential in islet regeneration, i.e.
      inhibition of beta-cell apoptosis and enhancement of beta-cell proliferation, yet
      involvement of GLP-1 in MEN1 related P-NET has not yet been demonstrated. The
      objective of this work was to investigate if normal sized islets of Men1
      heterozygous mice have increased Glucagon-like peptide-1 receptor (GLP-1R)
      expression compared to wild type islets, and if this increase is detectable in
      vivo with positron emission tomography (PET) using [68Ga]Ga-DO3A-VS-Cys40-Exendin
      4 (68Ga-Exendin-4). 68Ga-Exendin-4 showed potential for early lesion detection in
      MEN1 pancreas due to increased GLP1R expression.

PMID- 29335488
TI  - Distinct ERP profiles for auditory processing in infants at-risk for autism and
      language impairment.
AB  - Early identification of autism spectrum disorder (ASD) is crucial for the
      formulation of effective intervention programs. Language deficits may be a
      hallmark feature of ASD and language delay observed in ASD shows striking
      similarities to that observed in children with language impairment (LI). Auditory
      processing deficits are seen in both LI and ASD, however, they have not
      previously been compared directly using Event-Related Potentials (ERPs) in the
      two at-risk populations. This study aims to characterize infants at-risk for ASD
      (HR-ASD) at the electrophysiological level and to compare them with infants at
      risk for LI (HR-LI) and controls, to find specific markers with predictive value.
      At 12-month-old, auditory processing in HR-ASD, HR-LI and controls was
      characterized via ERP oddball paradigm. All infants were then evaluated at 20
      months, to investigate the associations between auditory processing and
      language/ASD-related outcomes. In both HR-ASD and HR-LI, mismatch response
      latency was delayed compared to controls, whereas only HR-ASD showed overall
      larger P3 amplitude compared to controls. Interestingly, these ERP measures
      correlated with later expressive vocabulary and M-CHAT critical items in the
      whole sample. These results may support the use of objective measurement of
      auditory processing to delineate pathophysiological mechanisms in ASD, as
      compared to LI.

PMID- 29335490
TI  - Study on regeneration of waste powder activated carbon through pyrolysis and its
      adsorption capacity of phosphorus.
AB  - The regeneration of WPAC through pyrolysis and its adsorption capacity of
      phosphorus were studied. The optimum conditions for WPAC regeneration were 650 
      degrees C and 2 h which resulted in a recovery of BET surface and total pore
      volume with a value of 1161.4 m2/g and 1.2176 m3/g. WPAC had a maximum PO43--P
      adsorption capacity of 9.65 mg/g which was 48.93% of PAC, while RWPAC had a
      maximum PO43--P adsorption capacity of 15.31 mg/g which was 77.64% of PAC. The
      kinetic analysis revealed that Langmuir model could well describe the adsorption
      process of PAC, WPAC and RWPAC on PO43--P and the PO43--P adsorption followed the
      pseudo-second-order model.

PMID- 29335489
TI  - Direct quantum process tomography via measuring sequential weak values of
      incompatible observables.
AB  - The weak value concept has enabled fundamental studies of quantum measurement
      and, recently, found potential applications in quantum and classical metrology.
      However, most weak value experiments reported to date do not require quantum
      mechanical descriptions, as they only exploit the classical wave nature of the
      physical systems. In this work, we demonstrate measurement of the sequential weak
      value of two incompatible observables by making use of two-photon quantum
      interference so that the results can only be explained quantum physically. We
      then demonstrate that the sequential weak value measurement can be used to
      perform direct quantum process tomography of a qubit channel. Our work not only
      demonstrates the quantum nature of weak values but also presents potential new
      applications of weak values in analyzing quantum channels and operations.

PMID- 29335491
TI  - Validation and optimization of the Systemic Inflammation-Based modified Glasgow
      Prognostic Score in predicting postoperative outcome of inflammatory bowel
      disease: preliminary data.
AB  - Systemic Inflammation-Based modified Glasgow Prognostic Score (mGPS) was
      developed as an objective tool to grade state of inflammation. However, the
      association between mGPS and postoperative complications for inflammatory bowel
      disease (IBD) patients was still unknown. In our study, 270 IBD patients [Crohn's
      disease (CD), n = 186; Ulcerative colitis (UC), n = 84] from January 2013 and
      January 2016 who underwent elective bowel resection were retrospectively
      analyzed, and, the levels of preoperative C-reactive protein (CRP) and albumin
      were included as parameters of mGPS. The incidence of overall postoperative
      complications was 44.81% (121/270), including 46.77% (87/186) of CD and 40.48%
      (34/84) of UC. According to multivariate analysis, mGPS (CD: OR = 3.47, p =
      0.003; UC: OR = 3.28, p = 0.019) was independently associated with an increased
      risk of postoperative complications. Patients with a higher mGPS also suffered
      longer postoperative stay and increased SSIs (both p < 0.05). Combining mGPS with
      neutrophil ratio improved its prognostic value with a better area under the curve
      (AUC), using receiver operating characteristic (ROC) method. Then we confirmed
      that mGPS was associated with postoperative complications in IBD patients
      undergoing elective bowel resection and the addition of neutrophil ratio enhanced
      its prognostic value.

PMID- 29335492
TI  - Assessing the effectiveness of NICE criteria for stratifying breast cancer risk
      in a UK cohort.
AB  - Breast cancer risk is a common indication for referral to clinical genetics
      services. UK National Institute of Health and Care Excellence (NICE) guidelines
      use family history (FH) to stratify by 10-year risk of breast cancer from age 40.
      Patients are stratified into population risk (PR, 10-year risk <3%), moderate
      (MR, 3-8%) and high risk (HR, >8%). Women at increased risk are offered screening
      at or prior to age 40. To assess the clinical effectiveness of current risk
      stratification, FH data were obtained for all unaffected women with a FH of
      breast cancer aged <50, referred to cancer genetics from 2000-2010. Patients were
      risk stratified by NICE criteria, identifying patients who subsequently developed
      breast cancer. A total of 1409 women had 15,414 patient years of follow-up.
      Thirty invasive breast cancers developed, 13 in MR and 13 in HR women. Kaplan
      Meier analysis demonstrated no significant difference in the rate of breast
      cancer development between PR and MR women from ages 40 to 49 (Log rank p =
      0.431). There was a significant difference between ages 40 and 49 years between
      PR and HR women (p = 0.036), but not on exclusion of BRCA mutation carriers (p =
      0.136). NICE absolute 10-year risk thresholds between ages 40 and 49 were not met
      in any risk group, when risk was estimated using the guidelines (PR = 0.82%, MR =
      1.68%, HR = 3.56%). Our data suggest that improved criteria are required for risk
      assessment prior to age 50 and screening resources may be best focussed on those
      with highly penetrant mutations in cancer risk genes.

PMID- 29335493
TI  - Biophysical feedbacks mediate carbonate chemistry in coastal ecosystems across
      spatiotemporal gradients.
AB  - Ocean acidification (OA) projections are primarily based on open ocean
      environments, despite the ecological importance of coastal systems in which
      carbonate dynamics are fundamentally different. Using temperate tide pools as a
      natural laboratory, we quantified the relative contribution of community
      composition, ecosystem metabolism, and physical attributes to spatiotemporal
      variability in carbonate chemistry. We found that biological processes were the
      primary drivers of local pH conditions. Specifically, non-encrusting producer
      dominated systems had the highest and most variable pH environments and the
      highest production rates, patterns that were consistent across sites spanning 11
      degrees  of latitude and encompassing multiple gradients of natural variability.
      Furthermore, we demonstrated a biophysical feedback loop in which net community
      production increased pH, leading to higher net ecosystem calcification. Extreme
      spatiotemporal variability in pH is, thus, both impacting and driven by
      biological processes, indicating that shifts in community composition and
      ecosystem metabolism are poised to locally buffer or intensify the effects of OA.

PMID- 29335494
TI  - Magnetic Chern Insulators in a monolayer of Transition Metal Trichalcogenides.
AB  - A monolayer of transition metal trichalcogenides has received a lot of attention
      as potential two dimensional magnetic materials. The system has a honeycomb
      structure of transition metal ions, where both spin-orbit coupling and electron
      correlation effect play an important role. Here, motivated by these transition
      metal series with effective doping or mixed valence case, we propose the possible
      realization of magnetic Chern insulators at quarter filled honeycomb lattice. We
      show that the interplay of intrinsic spin-orbit coupling and electron correlation
      opens a wide region of ferromagnetic Chern insulating phases in between metals
      and normal insulators. Within the mean field approximation, we present the phase
      diagram of a quarter filled Kane-Mele Hubbard model and also discuss the effects
      of Rashba spin-orbit coupling and nearest neighbor interactions on it.

PMID- 29335497
TI  - Interference induced enhancement of magneto-optical Kerr effect in ultrathin
      magnetic films.
AB  - We have studied the magneto-optical spectra of ultrathin magnetic films deposited
      on Si substrates coated with an oxide layer (SiOx). We find that the Kerr
      rotation angle and the ellipticity of ~1 nm thick CoFeB thin films, almost
      transparent to visible light, show a strong dependence on the thickness of the
      SiOx layer. The Kerr signal from the 1 nm CoFeB thin film can be larger than that
      of ~100 nm thick CoFeB films for a given SiOx thickness and light wavelength. The
      enhancement of the Kerr signal occurs when optical interference takes place
      within the SiOx layer. Interestingly, under such resonance condition, the
      measured Kerr signal is in some cases larger than the estimation despite the good
      agreement of the measured and calculated reflection amplitude. We infer the
      discrepancy originates from interface states that are distinct from the bulk
      characteristics. These results show that optical interference effect can be
      utilized to study the magneto-optical properties of ultrathin films.

PMID- 29335496
TI  - Localization and function of neurosecretory protein GM, a novel small secretory
      protein, in the chicken hypothalamus.
AB  - Recently, we discovered a novel cDNA encoding the precursor of a small secretory
      protein, neurosecretory protein GL (NPGL), in the hypothalamic infundibulum of
      chickens. NPGL plays an important role in the regulation of growth and feeding. A
      database search indicated that the NPGL gene has a paralogous gene:
      neurosecretory protein GM (NPGM), also in chickens. We identified cDNA encoding
      the NPGM precursor in chickens. Morphological analysis showed that NPGM
      containing cells are specifically localized in the medial mammillary nucleus (MM)
      and infundibular nucleus (IN) in the hypothalamus. In addition, we found that
      NPGM and NPGL are co-localized, especially in the MM. The expression levels of
      NPGM mRNA gradually decreased during post-hatch development, in contrast to those
      of NPGL mRNA. Moreover, we investigated the relationship between NPGM and other
      known factors. NPGM was found to be produced in histaminergic neurons in the MM.
      NPGM and histidine decarboxylase, a histamine-producing enzyme, displayed similar
      expression patterns during post-hatch development. Acute intracerebroventricular
      injection of NPGM decreased food intake, similar to the effect of histamine. To
      our knowledge, this is the first report of the localization and function of NPGM
      in the brain of vertebrates. These results will further advance the understanding
      mechanisms underlying energy homeostasis.

PMID- 29335495
TI  - Dysfunction of CD19+CD24hiCD27+ B regulatory cells in patients with bullous
      pemphigoid.
AB  - Bullous pemphigoid (BP) is an autoimmune blistering skin disease characterized by
      the production of autoantibodies against the hemidesmosomal protein BP180. B
      regulatory cells (Bregs) are crucial in maintaining self-tolerance and
      suppressing autoantibody production. However, it is still unclear whether the
      dysfunctions of Bregs contributes to the autoantibody production in BP patients.
      In this study, we found that CD19+CD24hiCD27+ Bregs and IL-10+CD19+ Bregs were
      significantly increased in the peripheral blood samples of BP patients compared
      with that in healthy controls. Moreover, compared to Bregs from healthy
      individuals, we found that Bregs from BP patients fails to suppress the
      production of specific anti-BP180 autoantibody when co-cultured with patient
      derived PBMCs. Additionally, Bregs from BP patients were defective in suppressing
      the CD4+ T cell proliferation and the cytokines expression (including IFN-gamma,
      TNF-alpha and IL-4). Notably, we found that patient-derived Bregs produced high
      level of TNF-alpha and the TNF inhibitor etanercept could inhibit the
      autoantibody production in the culture system in vitro. Our results indicate that
      Bregs from BP patient appear phenotypically pro-inflammatory by their cytokine
      profile and are defective in immunosuppressive function, which suggest that Bregs
      play a pro-inflammatory role rather than a regulatory role in the pathogenesis of
      BP.

PMID- 29335498
TI  - Stretchable Electrospun PVDF-HFP/Co-ZnO Nanofibers as Piezoelectric
      Nanogenerators.
AB  - Herein, we investigate the morphology, structure and piezoelectric performances
      of neat polyvinylidene fluoride hexafluoropropylene (PVDF-HFP) and PVDF-HFP/Co
      ZnO nanofibers, fabricated by electrospinning. An increase in the amount of
      crystalline beta-phase of PVDF-HFP has been observed with the increase in Co
      doped ZnO nanofiller concentration in the PVDF-HFP matrix. The dielectric
      constants of the neat PVDF-HFP and PVDF-HFP/2 wt.% Co-ZnO nanofibers are derived
      as 8 and 38 respectively. The flexible nanogenerator manipulated from the polymer
      nanocomposite (PVDF-HFP/Co-ZnO) exhibits an output voltage as high as 2.8 V
      compared with the neat PVDF-HFP sample (~120 mV). These results indicate that the
      investigated nanocomposite is appropriate for fabricating various flexible and
      wearable self-powered electrical devices and systems.

PMID- 29335500
TI  - Evidence of a cubic iron sub-lattice in t-CuFe2O4 demonstrated by X-ray
      Absorption Fine Structure.
AB  - Copper ferrite, belonging to the wide and technologically relevant class of
      spinel ferrites, was grown in the form of t-CuFe2O4 nanocrystals within a porous
      matrix of silica in the form of either an aerogel or a xerogel, and compared to a
      bulk sample. Extended X-ray absorption fine structure (EXAFS) spectroscopy
      revealed the presence of two different sub-lattices within the crystal structure
      of t-CuFe2O4, one tetragonal and one cubic, defined by the Cu2+ and Fe3+ ions
      respectively. Our investigation provides evidence that the Jahn-Teller
      distortion, which occurs on the Cu2+ ions located in octahedral sites, does not
      affect the coordination geometry of the Fe3+ ions, regardless of their location
      in octahedral or tetrahedral sites.

PMID- 29335499
TI  - Structure of a MacAB-like efflux pump from Streptococcus pneumoniae.
AB  - The spr0693-spr0694-spr0695 operon of Streptococcus pneumoniae encodes a putative
      ATP-binding cassette (ABC)-type efflux pump involved in the resistance of
      antibiotics and antimicrobial peptides. Here we report the crystal structures of
      Spr0694-0695 at 3.3 A and Spr0693 at 3.0 A resolution, revealing a MacAB-like
      efflux pump. The dimeric Spr0694-0695 adopts a non-canonical fold of ABC
      transporter, the transmembrane domain of which consists of eight tightly packed
      transmembrane helices with an insertion of extracellular domain between the first
      and second helices, whereas Spr0693 forms a nanotube channel docked onto the ABC
      transporter. Structural analyses combined with ATPase activity and antimicrobial
      susceptibility assays, enable us to propose a putative substrate-entrance tunnel
      with a lateral access controlled by a guard helix. Altogether, our findings
      provide structural insights and putative transport mechanism of a MacAB-like
      efflux pump in Gram-positive bacteria.

PMID- 29335501
TI  - Dual functional dinuclear platinum complex with selective reactivity towards c
      myc G-quadruplex.
AB  - G-quadruplexes (GQ) folded by the oncogenic G-rich sequences are the promising
      targets for developing anticancer therapeutic molecules. However, the current
      drug development mainly focused on non-covalent dynamic binders to stabilize GQ
      structures, while the covalent targeting from inorganic complexes via chelating
      principles, as a potent therapeutic strategy was surprisingly lack of
      exploration. Herein, a series of dinuclear platinum complexes, [(Pt(Dip)Cl)2(MU
      diamine)](NO3)2 (Dip: 4,7-diphenyl-1,10-phenanthroline), were designed to contain
      two dual-functional Pt cores connected by an alkyl linkage. Pt3 with
      nonanediamine linkage optimized the specific binding towards c-myc G-quadruplex
      via dual functional clamp on GQ as 1) non-covalently pi-stacking of aromatic
      ligands, and 2) two Pt(II) cores covalently chelated to guanines at both 3'- and
      5'-ends.

PMID- 29335502
TI  - The space charge limited current and huge linear magnetoresistance in silicon.
AB  - Huge magnetoresistance in space charge regime attracts broad interest on non
      equilibrium carrier transport under high electric field. However, the accurate
      fitting for the current-voltage curves from Ohmic to space charge regime under
      magnetic fields has not been achieved quantitatively. We conjecture that the
      localized intensive charge dynamic should be taken into consideration. Here, by
      introducing a field-dependent dielectric constant, for the first time, we
      successfully simulate the current-voltage curves of covalent crystal silicon
      wafers under different magnetic fields (0-1 Tesla). The simulation reveals that
      the optical phonon, instead of the acoustic phonon, plays a major role for the
      carriers transport under magnetic fields in space charge regime.

PMID- 29335503
TI  - Tuning charge carrier transport and optical birefringence in liquid-crystalline
      thin films: A new design space for organic light-emitting diodes.
AB  - Liquid-crystalline organic semiconductors exhibit unique properties that make
      them highly interesting for organic optoelectronic applications. Their optical
      and electrical anisotropies and the possibility to control the alignment of the
      liquid-crystalline semiconductor allow not only to optimize charge carrier
      transport, but to tune the optical property of organic thin-film devices as well.
      In this study, the molecular orientation in a liquid-crystalline semiconductor
      film is tuned by a novel blading process as well as by different annealing
      protocols. The altered alignment is verified by cross-polarized optical
      microscopy and spectroscopic ellipsometry. It is shown that a change in alignment
      of the liquid-crystalline semiconductor improves charge transport in single
      charge carrier devices profoundly. Comparing the current-voltage characteristics
      of single charge carrier devices with simulations shows an excellent agreement
      and from this an in-depth understanding of single charge carrier transport in two
      terminal devices is obtained. Finally, p-i-n type organic light-emitting diodes
      (OLEDs) compatible with vacuum processing techniques used in state-of-the-art
      OLEDs are demonstrated employing liquid-crystalline host matrix in the emission
      layer.

PMID- 29335504
TI  - Testing for the Presence of Correlation Changes in a Multivariate Time Series: A
      Permutation Based Approach.
AB  - Detecting abrupt correlation changes in multivariate time series is crucial in
      many application fields such as signal processing, functional neuroimaging,
      climate studies, and financial analysis. To detect such changes, several
      promising correlation change tests exist, but they may suffer from severe loss of
      power when there is actually more than one change point underlying the data. To
      deal with this drawback, we propose a permutation based significance test for
      Kernel Change Point (KCP) detection on the running correlations. Given a
      requested number of change points K, KCP divides the time series into K + 1
      phases by minimizing the within-phase variance. The new permutation test looks at
      how the average within-phase variance decreases when K increases and compares
      this to the results for permuted data. The results of an extensive simulation
      study and applications to several real data sets show that, depending on the
      setting, the new test performs either at par or better than the state-of-the art
      significance tests for detecting the presence of correlation changes, implying
      that its use can be generally recommended.

PMID- 29335505
TI  - PERK-mediated translational control is required for collagen secretion in
      chondrocytes.
AB  - As chondrocytes are highly secretory and they experience a variety of stresses,
      physiological unfolded protein response (UPR) signalling is essential for
      extracellular matrix (ECM) secretion and chondrogenesis. In the three branches of
      the UPR pathway, PERK governs the translational attenuation and transcriptional
      upregulation of amino acid and redox metabolism and induction of apoptosis. It
      was previously demonstrated that a defect of the PERK branch of the UPR
      signalling pathway causes the accumulation of unfolded proteins, leading to cell
      death without perturbing endoplasmic reticulum (ER)-to-Golgi transport in
      pancreatic beta cells. However, little is known about the role of PERK in
      chondrocytes. In this study, we found that PERK signalling is activated in
      chondrocytes, and inhibition of PERK reduces collagen secretion despite causing
      excessive collagen synthesis in the ER. Perk -/- mice displayed reduced collagen
      in articular cartilage but no differences in chondrocyte proliferation or
      apoptosis compared to the findings in wild-type mice. PERK inhibition increases
      misfolded protein levels in the ER, which largely hinder ER-to-Golgi transport.
      These results suggest that the translational control mediated by PERK is a
      critical determinant of ECM secretion in chondrocytes.

PMID- 29335506
TI  - Transcriptome profiling during mangrove viviparity in response to abscisic acid.
AB  - Mangrove plants adapt to coastal tidal mudflats with specially evolved viviparity
      seed development. However, very little is known about the genetic and molecular
      mechanisms of mangrove viviparity. Here, we tested a hypothesis that plant
      hormone abscisic acid (ABA) plays a significant role in precocious germination of
      viviparous Kandelia obovata seeds by exogenous applications. Through
      transcriptome analysis of ABA treated seeds, it was found that ABA repressed
      mangrove fruit growth and development, and there were thousands of genes
      differentially expressed. As a result, dynamics of the pathways were dramatically
      altered. In particular, "Plant hormone signal transduction" and "MAPK signaling
      pathway" were represented significantly. Among differentially expressed genes,
      some key genes of ABA signal transduction were induced, while ABA biosynthesis
      genes were repressed. Take ABI1 and ABI2, key negative regulators in ABA signal
      pathway, as examples, homologous alignment and a phylogenetic tree in various
      species showed that ABI1 and ABI2 are highly conserved among various species. The
      functional similarity of these genes was confirmed by transgenic work in
      Arabidopsis. Taken together, ABA inhibited mangrove viviparity, but mangroves
      developed a mechanism to prevent accidently increase of ABA in the harsh
      environment for maintaining viviparous reproductive strategy.

PMID- 29335508
TI  - Label-Free, High Resolution, Multi-Modal Light Microscopy for Discrimination of
      Live Stem Cell Differentiation Status.
AB  - A label-free microscopy method for assessing the differentiation status of stem
      cells is presented with potential application for characterization of therapeutic
      stem cell populations. The microscopy system is capable of characterizing live
      cells based on the use of evanescent wave microscopy and quantitative phase
      contrast (QPC) microscopy. The capability of the microscopy system is
      demonstrated by studying the differentiation of live immortalised neonatal mouse
      neural stem cells over a 15 day time course. Metrics extracted from microscope
      images are assessed and images compared with results from endpoint immuno
      staining studies to illustrate the system's performance. Results demonstrate the
      potential of the microscopy system as a valuable tool for cell biologists to
      readily identify the differentiation status of unlabelled live cells.

PMID- 29335507
TI  - Highly conserved molecular pathways, including Wnt signaling, promote functional
      recovery from spinal cord injury in lampreys.
AB  - In mammals, spinal cord injury (SCI) leads to dramatic losses in neurons and
      synaptic connections, and consequently function. Unlike mammals, lampreys are
      vertebrates that undergo spontaneous regeneration and achieve functional recovery
      after SCI. Therefore our goal was to determine the complete transcriptional
      responses that occur after SCI in lampreys and to identify deeply conserved
      pathways that promote regeneration. We performed RNA-Seq on lamprey spinal cord
      and brain throughout the course of functional recovery. We describe complex
      transcriptional responses in the injured spinal cord, and somewhat surprisingly,
      also in the brain. Transcriptional responses to SCI in lampreys included
      transcription factor networks that promote peripheral nerve regeneration in
      mammals such as Atf3 and Jun. Furthermore, a number of highly conserved axon
      guidance, extracellular matrix, and proliferation genes were also differentially
      expressed after SCI in lampreys. Strikingly, ~3% of differentially expressed
      transcripts belonged to the Wnt pathways. These included members of the Wnt and
      Frizzled gene families, and genes involved in downstream signaling.
      Pharmacological inhibition of Wnt signaling inhibited functional recovery,
      confirming a critical role for this pathway. These data indicate that molecular
      signals present in mammals are also involved in regeneration in lampreys,
      supporting translational relevance of the model.

PMID- 29335510
TI  - TiO2 Nanoribbons/Carbon Nanotubes Composite with Enhanced Photocatalytic
      Activity; Fabrication, Characterization, and Application.
AB  - TiO2 nanoribbons (TiO2 NRs) loaded with FeCo-Al2O3 catalyst were synthesized and
      used as a precursor in the synthesis of TiO2 nanoribbons/carbon nanotubes (TiO2
      NRs/CNTs) composite by a chemical vapor deposition (CVD) method. TiO2 NRs and
      TiO2 NRs/CNTs composite were characterized by XRD, FT-IR, TEM, SEM, EDX and UV
      Vis spectrophotometer. The results revealed the formation of TiO2-B and hydrogen
      titanate nanoribbon like structures by the hydrothermal treatment. After loading
      TiO2 NRs by FeCo-Al2O3 catalyst and the CVD growth of carbon nanotubes, the
      synthetic TiO2 nanoribbons converted entirely to TiO2-B nanoribbons with nanopits
      structure. The composite composed of tube-like nanostructures forming an
      interlocked network from CNTs and TiO2-B NRs. The composite shows a relatively
      red-shifted band gap (3.09 eV), broader and stronger UV absorption band relative
      to TiO2 NRs. The photocatalytic properties of TiO2 NRs and TiO2 NRs/CNTs
      composite were studied under sunlight irradiation. The photocatalytic degradation
      of methylene blue (MB) dye was investigated as a function of contact time, dye
      concentration, and catalyst dose. The kinetics and mechanisms of degradation were
      discussed. TiO2 NRs/CNTs composite showed higher stability after six runs and 50%
      shorter irradiation time than TiO2 NRs photocatalyst.

PMID- 29335511
TI  - Publisher Correction: Broad modulus range nanomechanical mapping by magnetic
      drive soft probes.
AB  - In the original version of this Article, the text labels on the bottom-right
      graph in Fig. 1c were inadvertently displaced during the production process. This
      has now been corrected in both the PDF and HTML versions of the Article.

PMID- 29335509
TI  - Salient type 1 interleukin 1 receptor expression in peripheral non-immune cells.
AB  - Interleukin 1 is a pleiotropic cytokine that mediates diverse functions through
      its receptor, type I interleukin 1 receptor (IL-1R1). Most previous studies have
      focused on the expression and function of IL-1R1 in immune cells. Here we
      performed a comprehensive mapping of IL-1R1 distribution in multiple peripheral
      tissues using our IL-1R1 reporter (IL-1R1GR/GR) mice. This method yielded the
      highest sensitivity of in situ detection of IL-1R1 mRNA and protein. Besides
      validating previously reported IL-1R1 expression in the endocrine tissues
      including pituitary and pancreas, our results refuted previously reported
      exclusive IL-1R1 expression in neurons of the spinal cord dorsal horn and dorsal
      root ganglia (DRG). Instead, IL-1R1 expression was detected in endothelial cells
      within DRG, spinal cord, pancreas, colon, muscles and many immune organs. In
      addition, gp38+ fibroblastic reticular cells (FRCs), rather than tissue
      macrophages or other immune cells, were found to express high levels of IL-1R1 in
      colon and many immune organs. A functional test of spleen FRCs showed that they
      responded rapidly to systemic IL-1beta stimulation in vivo. Taken together, this
      study provides a rigorous re-examination of IL-1R1 expression in peripheral
      tissues and reveals tissue FRCs as a previously unappreciated novel high IL-1R1
      expressing cell type in peripheral IL-1 signaling.

PMID- 29335512
TI  - Label-free photoacoustic imaging of human palmar vessels: a structural
      morphological analysis.
AB  - We analysed the vascular morphology of the palm using a photoacoustic tomography
      (PAT) instrument with a hemispherical detector array. The three-dimensional (3D)
      morphology of blood vessels was determined noninvasively. Overall, 12 females and
      11 males were recruited as healthy volunteers. Their ages were distributed almost
      evenly from 22 to 59 years. In all cases, many vascular networks were observed
      just beneath the skin and were determined to be veins anatomically. To analyse
      the major arteries, the layer containing the subcutaneous venous network was
      removed from the image. The analysis focused on the common and proper palmar
      digital arteries. We used the curvature of these arteries as a parameter to
      analyse their morphologies. There was no significant difference in the curvature
      between genders when comparing the subjects as a whole. The blood vessel
      curvature increased with age. Good agreement was found between the 3D numerical
      analysis results and the subjective evaluation of the two-dimensional (2D)
      projection image. The PAT system enabled visualization of the 3D features of
      blood vessels in the palm and noninvasive analysis of arterial tortuousness.

PMID- 29335513
TI  - Optimal ranges of variables for an effective adsorption of lead(II) by the
      agricultural waste pomelo (Citrus grandis) peels using Doehlert designs.
AB  - The capacity of pomelo peels' adsorption on lead(II) from aqueous solutions
      without modifications was investigated and confirmed. Four variables in this
      study, pH, temperature, time and initial concentration of lead(II), significantly
      affected the adsorption rate of pomelo peels. The prediction model and optimal
      ranges of optimized variables were given by Doehlert designs, which made the
      selection of variables rapid, flexible and effortless to obtain an adsorption
      rate reaching 99.9% and 20 mg/L for initial lead(II) concentration, 3 for pH, 50 
      degrees C for temperature and 210 min for time was a choice. The higher
      correlation coefficient as well as the more consistent value of experimental
      equilibrium adsorption capacity of the pseudo-first-order model suggested it bore
      a better prediction of the adsorption kinetics than the pseudo-second-order
      model. Langmuir model indicated the adsorption mechanism of pomelo peels was
      monolayer sorption with the help of both physical adsorption and chemical
      bonding, which were demonstrated by scanning electron microscopy and Fourier
      transform-infrared, respectively. The ability of pomelo peels to adsorb lead(II)
      from aqueous solutions was not interfered with the presence of calcium(II),
      magnesium(II), copper(II) and zinc(II). Pomelo peels had the potential to be
      utilized in the simultaneous adsorption of toxic heavy metal ions.

PMID- 29335514
TI  - Monitoring single-cell gene regulation under dynamically controllable conditions
      with integrated microfluidics and software.
AB  - Much is still not understood about how gene regulatory interactions control cell
      fate decisions in single cells, in part due to the difficulty of directly
      observing gene regulatory processes in vivo. We introduce here a novel integrated
      setup consisting of a microfluidic chip and accompanying analysis software that
      enable long-term quantitative tracking of growth and gene expression in single
      cells. The dual-input Mother Machine (DIMM) chip enables controlled and
      continuous variation of external conditions, allowing direct observation of gene
      regulatory responses to changing conditions in single cells. The Mother Machine
      Analyzer (MoMA) software achieves unprecedented accuracy in segmenting and
      tracking cells, and streamlines high-throughput curation with a novel leveraged
      editing procedure. We demonstrate the power of the method by uncovering several
      novel features of an iconic gene regulatory program: the induction of Escherichia
      coli's lac operon in response to a switch from glucose to lactose.

PMID- 29335515
TI  - Ultrafast consolidation of bulk nanocrystalline titanium alloy through ultrasonic
      vibration.
AB  - Nanocrystalline (NC) materials have fascinating physical and chemical properties,
      thereby they exhibit great prospects in academic and industrial fields. Highly
      efficient approaches for fabricating bulk NC materials have been pursued
      extensively over past decades. However, the instability of nanograin, which is
      sensitive to processing parameters (such as temperature and time), is always a
      challenging issue to be solved and remains to date. Herein, we report an
      ultrafast nanostructuring strategy, namely ultrasonic vibration consolidation
      (UVC). The strategy utilizes internal friction heat, generated from mutually
      rubbing between Ti-based metallic glass powders, to heat the glassy alloy rapidly
      through its supercooled liquid regime, and accelerated viscous flow bonds the
      powders together. Consequently, bulk NC-Ti alloy with grain size ranging from 10
      to 70 nm and nearly full density is consolidated in 2 seconds. The novel
      consolidation approach proposed here offers a general and highly efficient
      pathway for manufacturing bulk nanomaterials.

PMID- 29335516
TI  - An evaluation of the effect of pulse-shape on grey and white matter stimulation
      in the rat brain.
AB  - Despite the current success of neuromodulation, standard biphasic, rectangular
      pulse shapes may not be optimal to achieve symptom alleviation. Here, we compared
      stimulation efficiency (in terms of charge) between complex and standard pulses
      in two areas of the rat brain. In motor cortex, Gaussian and interphase gap
      stimulation (IPG) increased stimulation efficiency in terms of charge per phase
      compared with a standard pulse. Moreover, IPG stimulation of the deep
      mesencephalic reticular formation in freely moving rats was more efficient
      compared to a standard pulse. We therefore conclude that complex pulses are
      superior to standard stimulation, as less charge is required to achieve the same
      behavioral effects in a motor paradigm. These results have important implications
      for the understanding of electrical stimulation of the nervous system and open
      new perspectives for the design of the next generation of safe and efficient
      neural implants.

PMID- 29335517
TI  - A versatile MOF-based trap for heavy metal ion capture and dispersion.
AB  - Current technologies for removing heavy metal ions are typically metal ion
      specific. Herein we report the development of a broad-spectrum heavy metal ion
      trap by incorporation of ethylenediaminetetraacetic acid into a robust metal
      organic framework. The capture experiments for a total of 22 heavy metal ions,
      covering hard, soft, and borderline Lewis metal ions, show that the trap is very
      effective, with removal efficiencies of >99% for single-component adsorption,
      multi-component adsorption, or in breakthrough processes. The material can also
      serve as a host for metal ion loading with arbitrary selections of metal ion
      amounts/types with a controllable uptake ratio to prepare well-dispersed single
      or multiple metal catalysts. This is supported by the excellent performance of
      the prepared Pd2+-loaded composite toward the Suzuki coupling reaction. This work
      proposes a versatile heavy metal ion trap that may find applications in the
      fields of separation and catalysis.

PMID- 29335518
TI  - Recurrence patterns after maximal surgical resection and postoperative
      radiotherapy in anaplastic gliomas according to the new 2016 WHO classification.
AB  - We assessed the appropriateness of current radiotherapy volume for WHO grade III
      gliomas. The records of 73 patients with WHO grade III gliomas who received
      postoperative radiotherapy between 2001 and 2013 were retrospectively reviewed.
      Based on the 2016 WHO classification, 25/73 (34.2%) patients had anaplastic
      oligodendroglioma (AO), IDH-mutant and 1p/19q-codeleted; 11/73 (15.1%) patients
      had anaplastic astrocytoma, IDH-mutant; and 37/73 (50.7%) patients had anaplastic
      astrocytoma, IDH-wildtype. The extent of resection (EOR) was total in 43 patients
      (58.9%). The median follow-up time was 84 months. The 5-year overall survival was
      65.4%. Of 31 patients with documented recurrences, 20 (64.5%) had infield gross
      tumor volume (GTV) failure, six (19.4%) had clinical target volume (CTV)/marginal
      failure, and five (16.1%) had outfield failure/seeding. In 13 recurrences among
      43 patients who underwent gross total resection (GTR), six (46.2%) had infield
      CTV/marginal failure. However, among 30 patients for whom GTR was not conducted,
      infield GTV failure was dominant (77.8%). Seventeen patients with AO, IDH-mutant
      and 1p/19q-codeleted who underwent GTR experienced no recurrence. In conclusion,
      maximal surgical resection and postoperative radiotherapy resulted in a favorable
      prognosis, especially in patients with GTR, IDH mutation, and 1p/19q codeletion.
      Patterns of failure differed by EOR.

PMID- 29335519
TI  - Metabolic reprogramming by PCK1 promotes TCA cataplerosis, oxidative stress and
      apoptosis in liver cancer cells and suppresses hepatocellular carcinoma.
AB  - Phosphoenolpyruvate carboxykinase (PEPCK or PCK) catalyzes the first rate
      limiting step in hepatic gluconeogenesis pathway to maintain blood glucose
      levels. Mammalian cells express two PCK genes, encoding for a cytoplasmic (PCPEK
      C or PCK1) and a mitochondrial (PEPCK-M or PCK2) isoforms, respectively.
      Increased expressions of both PCK genes are found in cancer of several organs,
      including colon, lung, and skin, and linked to increased anabolic metabolism and
      cell proliferation. Here, we report that the expressions of both PCK1 and PCK2
      genes are downregulated in primary hepatocellular carcinoma (HCC) and low PCK
      expression was associated with poor prognosis in patients with HCC. Forced
      expression of either PCK1 or PCK2 in liver cancer cell lines results in severe
      apoptosis under the condition of glucose deprivation and suppressed liver
      tumorigenesis in mice. Mechanistically, we show that the pro-apoptotic effect of
      PCK1 requires its catalytic activity. We demonstrate that forced PCK1 expression
      in glucose-starved liver cancer cells induced TCA cataplerosis, leading to energy
      crisis and oxidative stress. Replenishing TCA intermediate alpha-ketoglutarate or
      inhibition of reactive oxygen species production blocked the cell death caused by
      PCK expression. Taken together, our data reveal that PCK1 is detrimental to
      malignant hepatocytes and suggest activating PCK1 expression as a potential
      treatment strategy for patients with HCC.

PMID- 29335520
TI  - HPV16 E6 and E7 upregulate the histone lysine demethylase KDM2B through the c
      MYC/miR-146a-5p axys.
AB  - Persistent infection by high-risk human papillomaviruses (HPVs) is associated
      with the development of cervical cancer and a subset of anogenital and head and
      neck squamous cell carcinomas. Abnormal expression of cellular microRNAs (miRNAs)
      plays an important role in the development of cancer, including HPV-related
      tumors. In this study, we demonstrated that miR-146a-5p was down-regulated by E6
      and, less efficiently, by E7 of high-risk HPV16 in keratinocytes and the presence
      of low levels of this miRNA in cervical carcinoma cell lines and in high-risk HPV
      positive cervical specimens. Down-regulation of miR-146a-5p was mediated at least
      in part by the transcription repressor c-MYC, through binding sites in the miR
      146a promoter. Overexpression of miR-146a-5p significantly inhibited
      proliferation and migration of keratinocytes and cervical cancer cells. The
      histone demethylase KDM2B was validated as a new direct target of miR-146a-5p and
      two putative binding sites for miR-146a-5p were identified in its 3'UTR sequence.
      Western blot analysis and immunohistochemistry showed that KDM2B was
      overexpressed in HPV16 E6/E7-positive keratinocytes, in cervical cancer cell
      lines, and in a subset of invasive cervical carcinomas and HPV-positive laryngeal
      squamous cell carcinomas. In these tumors, KDM2B overexpression was associated
      with c-MYC copy number gain. In vitro, silencing of KDM2B inhibited proliferation
      of cervical cancer cells. In conclusion, this study identified a novel player,
      the hystone demethylase KDM2B, in HPV-mediated tumorigenesis. E6 and, less
      efficiently, E7 of high-risk HPV16 up-regulated KDM2B expression in human
      keratinocytes through a pathway involving overexpression of c-MYC, which in turn
      downregulated miR-146a-5p.

PMID- 29335521
TI  - Non-canonical roles of PFKFB3 in regulation of cell cycle through binding to
      CDK4.
AB  - There is growing interest in studying the molecular mechanisms of crosstalk
      between cancer metabolism and the cell cycle. 6-phosphate fructose-2
      kinase/fructose-2,6-bisphosphatase-3 (PFKFB3) is a well-known glycolytic
      activator that plays an important role in tumorigenesis. We investigated whether
      PFKFB3 was directly involved in oncogenic signaling networks. Mass Spectrometry
      showed that PFKFB3 interacts with cyclin-dependent kinase (CDK) 4, which controls
      the transition from G1 phase to S phase of the cell cycle. Further analysis
      indicated that lysine 147 was a key site for the binding of PFKBFB3 to CDK4.
      PFKFB3 binding resulted in the accumulation of CDK4 protein by inhibiting
      ubiquitin proteasome degradation mediated by the heat shock protein 90-Cdc37-CDK4
      complex. The proteasome-dependent degradation of CDK4 was accelerated by
      disrupting the interaction of PFKFB3 with CDK4 by mutating lysine (147) to
      alanine. Blocking PFKFB3-CDK4 interaction improved the therapeutic effect of FDA
      approved CDK4 inhibitor palbociclib on breast cancer. These findings suggest that
      PFKFB3 is a hub for coordinating cell cycle and glucose metabolism. Combined
      targeting of PFKFB3 and CDK4 may be new strategy for breast cancer treatment.

PMID- 29335522
TI  - Pyruvate kinase M2 promotes pancreatic ductal adenocarcinoma invasion and
      metastasis through phosphorylation and stabilization of PAK2 protein.
AB  - Pyruvate kinase muscle isozymes (PKMs) have crucial roles in regulating metabolic
      changes during carcinogenesis. A switch from PKM1 to PKM2 isoform was thought to
      lead to aerobic glycolysis promoting carcinogenesis, and was considered as one of
      the cancer signatures. However, recent evidence has argued against the existence
      of PKM isoform switch and related metabolic effects during cancer progression. We
      compared the effects of PKM1 and PKM2 in cell invasiveness and metastasis of
      pancreatic ductal adenocarcinoma (PDAC). Both PKM1 and PKM2 expression affected
      cell migration and invasion abilities of PDAC cells, but only knockdown of PKM2
      suppressed metastasis in a xenograft model. By comparing the established PKM2
      mutants in the regulation of cell invasion, we found that PKM2 may control cell
      mobility through its protein kinase and phopho-peptide binding abilities. Further
      survey for PKM2-associated proteins identified PAK2 as a possible phosphorylation
      target in PDAC. In vitro binding and kinase assays revealed that PKM2 directly
      phosphorylated PAK2 at Ser20, Ser141, and Ser192/197. Knockdown of PKM2 decreased
      PAK2 protein half-life by increasing ubiquitin-dependent proteasomal degradation.
      Moreover, we identified PAK2 as an HSP90 client protein and the mutation at
      Ser192/197 of PAK2 reduced PAK2-HSP90 association. Knockdown of PAK2 diminished
      in vitro cell mobility and in vivo metastatic ability of PKM2 overexpressed PDAC
      cells. PKM2 and PAK2 protein expression also positively correlated with each
      other in PDAC tissues. Our findings indicate that PKM2-PAK2 regulation is
      critical for developing metastasis in PDAC, and suggest that targeting the
      PKM2/HSP90/PAK2 complex has a potential therapeutic value in this deadly disease.

PMID- 29335524
TI  - Kidney cancer in 2017: Challenging and refining treatment paradigms.

PMID- 29335523
TI  - miR-139-5p inhibits aerobic glycolysis, cell proliferation, migration, and
      invasion in hepatocellular carcinoma via a reciprocal regulatory interaction with
      ETS1.
AB  - Cancer cells have metabolic features that allow them to preferentially metabolize
      glucose through aerobic glycolysis, providing them with a progression advantage.
      However, microRNA (miRNA) regulation of aerobic glycolysis in cancer cells has
      not been extensively investigated. We addressed this in the present study by
      examining the regulation of miR-139-5p on aerobic glycolysis of hepatocellular
      carcinoma (HCC) using clinical specimens, HCC cells, and a mouse xenograft model.
      We found that overexpressing miR-139-5p restrained aerobic glycolysis,
      suppressing proliferation, migration, and invasion in HCC cells. miR-139-5p
      regulated hexokinase 1 (HK1) and 6-phosphofructo-2-kinase/fructose-2,6
      biphosphatase 3 (PFKFB3) expression by directly targeting the transcription
      factor ETS1, which bound to the promoters of the HK1 and PFKFB3 genes. miR-139-5p
      induced aerobic glycolysis, proliferation, migration, and invasion were reversed
      by ETS1 overexpression, while ETS1 silencing induced the expression of miR-139-5p
      via a post-transcriptional regulation mode involving Drosha. miR-139-5p
      expression was reduced in HCC compared to para-carcinoma tissue, which was
      confirmed in The Cancer Genome Atlas and GSE54751 HCC cohorts. Notably, the lower
      expression of mir-139 was correlated with worse prognosis. These outcomes
      indicate that reciprocal regulatory interactions between miR-139-5p and ETS1
      modulate aerobic glycolysis, proliferation, and metastasis in HCC cells,
      suggesting new targets for HCC treatment.

PMID- 29335525
TI  - Urothelial cancer: Optimizing and integrating cisplatin-based chemotherapy across
      the disease spectrum.

PMID- 29335526
TI  - Prostate cancer: Race and prostate cancer personalized medicine: the future.

PMID- 29335527
TI  - Myosin-Va is required for preciliary vesicle transportation to the mother
      centriole during ciliogenesis.
AB  - Primary cilia play essential roles in signal transduction and development. The
      docking of preciliary vesicles at the distal appendages of a mother centriole is
      an initial/critical step of ciliogenesis, but the mechanisms are unclear. Here,
      we demonstrate that myosin-Va mediates the transportation of preciliary vesicles
      to the mother centriole and reveal the underlying mechanism. We also show that
      the myosin-Va-mediated transportation of preciliary vesicles is the earliest
      event that defines the onset of ciliogenesis. Depletion of myosin-Va
      significantly inhibits the attachment of preciliary vesicles to the distal
      appendages of the mother centriole and decreases cilia assembly. Myosin-Va
      functions upstream of EHD1- and Rab11-mediated ciliary vesicle formation.
      Importantly, dynein mediates myosin-Va-associated preciliary vesicle
      transportation to the pericentrosomal region along microtubules, while myosin-Va
      mediates preciliary vesicle transportation from the pericentrosomal region to the
      distal appendages of the mother centriole via the Arp2/3-associated branched
      actin network.

PMID- 29335528
TI  - EXD2 governs germ stem cell homeostasis and lifespan by promoting mitoribosome
      integrity and translation.
AB  - Mitochondria are subcellular organelles that are critical for meeting the
      bioenergetic and biosynthetic needs of the cell. Mitochondrial function relies on
      genes and RNA species encoded both in the nucleus and mitochondria, and on their
      coordinated translation, import and respiratory complex assembly. Here, we
      characterize EXD2 (exonuclease 3'-5' domain-containing 2), a nuclear-encoded
      gene, and show that it is targeted to the mitochondria and prevents the aberrant
      association of messenger RNAs with the mitochondrial ribosome. Loss of EXD2
      results in defective mitochondrial translation, impaired respiration, reduced ATP
      production, increased reactive oxygen species and widespread metabolic
      abnormalities. Depletion of the Drosophila melanogaster EXD2 orthologue (CG6744)
      causes developmental delays and premature female germline stem cell attrition,
      reduced fecundity and a dramatic extension of lifespan that is reversed with an
      antioxidant diet. Our results define a conserved role for EXD2 in mitochondrial
      translation that influences development and ageing.

PMID- 29335529
TI  - Transient Scute activation via a self-stimulatory loop directs enteroendocrine
      cell pair specification from self-renewing intestinal stem cells.
AB  - The process through which multiple types of cell-lineage-restricted progenitor
      cells are specified from multipotent stem cells is unclear. Here we show that, in
      intestinal stem cell lineages in adult Drosophila, in which the Delta-Notch
      signalling-guided progenitor cell differentiation into enterocytes is the default
      mode, the specification of enteroendocrine cells (EEs) is initiated by transient
      Scute activation in a process driven by transcriptional self-stimulation combined
      with a negative feedback regulation between Scute and Notch targets. Scute
      activation induces asymmetric intestinal stem cell divisions that generate EE
      progenitor cells. The mitosis-inducing and fate-inducing activities of Scute
      guide each EE progenitor cell to divide exactly once prior to its terminal
      differentiation, yielding a pair of EEs. The transient expression of a fate
      inducer therefore specifies both type and numbers of committed progenitor cells
      originating from stem cells, which could represent a general mechanism used for
      diversifying committed progenitor cells from multipotent stem cells.

PMID- 29335530
TI  - Segregation of mitochondrial DNA heteroplasmy through a developmental genetic
      bottleneck in human embryos.
AB  - Mitochondrial DNA (mtDNA) mutations cause inherited diseases and are implicated
      in the pathogenesis of common late-onset disorders, but how they arise is not
      clear1,2. Here we show that mtDNA mutations are present in primordial germ cells
      (PGCs) within healthy female human embryos. Isolated PGCs have a profound
      reduction in mtDNA content, with discrete mitochondria containing ~5 mtDNA
      molecules. Single-cell deep mtDNA sequencing of in vivo human female PGCs showed
      rare variants reaching higher heteroplasmy levels in late PGCs, consistent with
      the observed genetic bottleneck. We also saw the signature of selection against
      non-synonymous protein-coding, tRNA gene and D-loop variants, concomitant with a
      progressive upregulation of genes involving mtDNA replication and transcription,
      and linked to a transition from glycolytic to oxidative metabolism. The
      associated metabolic shift would expose deleterious mutations to selection during
      early germ cell development, preventing the relentless accumulation of mtDNA
      mutations in the human population predicted by Muller's ratchet. Mutations
      escaping this mechanism will show shifts in heteroplasmy levels within one human
      generation, explaining the extreme phenotypic variation seen in human pedigrees
      with inherited mtDNA disorders.

PMID- 29335531
TI  - Publisher Correction: Coherent diffractive imaging of single helium nanodroplets
      with a high harmonic generation source.
AB  - In the original version of this Article, the affiliation for Luca Poletto was
      incorrectly given as 'European XFEL GmbH, Holzkoppel 4, 22869 Schenefeld,
      Hamburg, Germany', instead of the correct 'CNR, Istituto di Fotonica e
      Nanotecnologie Padova, Via Trasea 7, 35131 Padova, Italy'. This has now been
      corrected in both the PDF and HTML versions of the Article.

PMID- 29335532
TI  - Intelligent image-based in situ single-cell isolation.
AB  - Quantifying heterogeneities within cell populations is important for many fields
      including cancer research and neurobiology; however, techniques to isolate
      individual cells are limited. Here, we describe a high-throughput, non
      disruptive, and cost-effective isolation method that is capable of capturing
      individually targeted cells using widely available techniques. Using high
      resolution microscopy, laser microcapture microscopy, image analysis, and machine
      learning, our technology enables scalable molecular genetic analysis of single
      cells, targetable by morphology or location within the sample.

PMID- 29335533
TI  - Fc-modified exenatide-loaded nanoparticles for oral delivery to improve
      hypoglycemic effects in mice.
AB  - To improve the oral efficiency of exenatide, we prepared polyethylene glycol
      poly(lactic-co-glycolic acid) (PEG-PLGA) NPs modified with Fc (NPs-Fc) for
      exenatide oral delivery. Exenatide was encapsulated into the NPs by the w/o/w
      emulsion-solvent evaporation method. The particle size of the NPs-Fc was
      approximately 30 nm larger than that of the unmodified NPs with polydispersity
      indices in a narrow range (PDIs; PDI < 0.3) as detected by DLS, and the highest
      encapsulation efficiency of exenatide in the NPs was greater than 80%. Fc
      conjugated NPs permeated Caco-2 cells faster and to a greater extent compared to
      unmodified NPs, as verified by CLSM and flow cytometry. Hypoglycemic effect
      studies demonstrated that oral administration of exenatide-loaded PEG-PLGA NPs
      modified by an Fc group extended the hypoglycemic effects compared with s.c.
      injection of the exenatide solution. Fluorescence-labeled NPs were used to
      investigate the effects of Fc targeting, and the results demonstrated that the
      NPs-Fc stayed in the gastrointestinal tract for a longer time in comparison with
      the unmodified NPs, as shown by the whole-body fluorescence images and
      fluorescence images of the dissected organs detected by in vivo imaging in live
      mice. Therefore, Fc-targeted nano-delivery systems show great promise for oral
      peptide/protein drug delivery.

PMID- 29335534
TI  - Cell-type specific potent Wnt signaling blockade by bispecific antibody.
AB  - Cell signaling pathways are often shared between normal and diseased cells. How
      to achieve cell type-specific, potent inhibition of signaling pathways is a major
      challenge with implications for therapeutic development. Using the Wnt/beta
      catenin signaling pathway as a model system, we report here a novel and generally
      applicable method to achieve cell type-selective signaling blockade. We
      constructed a bispecific antibody targeting the Wnt co-receptor LRP6 (the
      effector antigen) and a cell type-associated antigen (the guide antigen) that
      provides the targeting specificity. We found that the bispecific antibody
      inhibits Wnt-induced reporter activities with over one hundred-fold enhancement
      in potency, and in a cell type-selective manner. Potency enhancement is dependent
      on the expression level of the guide antigen on the target cell surface and the
      apparent affinity of the anti-guide antibody. Both internalizing and non
      internalizing guide antigens can be used, with internalizing bispecific antibody
      being able to block signaling by all ligands binding to the target receptor due
      to its removal from the cell surface. It is thus feasible to develop bispecific
      based therapeutic strategies that potently and selectively inhibit signaling
      pathways in a cell type-selective manner, creating opportunity for therapeutic
      targeting.

PMID- 29335535
TI  - A multi-omics study of the grapevine-downy mildew (Plasmopara viticola)
      pathosystem unveils a complex protein coding- and noncoding-based arms race
      during infection.
AB  - Fungicides are applied intensively to prevent downy mildew infections of
      grapevines (Vitis vinifera) with high impact on the environment. In order to
      develop alternative strategies we sequenced the genome of the oomycete pathogen
      Plasmopara viticola causing this disease. We show that it derives from a
      Phytophthora-like ancestor that switched to obligate biotrophy by losing genes
      involved in nitrogen metabolism and gamma-Aminobutyric acid catabolism. By
      combining multiple omics approaches we characterized the pathosystem and
      identified a RxLR effector that trigger an immune response in the wild species V.
      riparia. This effector is an ideal marker to screen novel grape resistant
      varieties. Our study reveals an unprecedented bidirectional noncoding RNA-based
      mechanism that, in one direction might be fundamental for P. viticola to
      proficiently infect its host, and in the other might reduce the effects of the
      infection on the plant.

PMID- 29335536
TI  - Characterizing the dynamics underlying global spread of epidemics.
AB  - Over the past few decades, global metapopulation epidemic simulations built with
      worldwide air-transportation data have been the main tool for studying how
      epidemics spread from the origin to other parts of the world (e.g., for pandemic
      influenza, SARS, and Ebola). However, it remains unclear how disease epidemiology
      and the air-transportation network structure determine epidemic arrivals for
      different populations around the globe. Here, we fill this knowledge gap by
      developing and validating an analytical framework that requires only basic
      analytics from stochastic processes. We apply this framework retrospectively to
      the 2009 influenza pandemic and 2014 Ebola epidemic to show that key epidemic
      parameters could be robustly estimated in real-time from public data on local and
      global spread at very low computational cost. Our framework not only elucidates
      the dynamics underlying global spread of epidemics but also advances our
      capability in nowcasting and forecasting epidemics.

PMID- 29335537
TI  - A bony-crested Jurassic dinosaur with evidence of iridescent plumage highlights
      complexity in early paravian evolution.
AB  - The Jurassic Yanliao theropods have offered rare glimpses of the early paravian
      evolution and particularly of bird origins, but, with the exception of the
      bizarre scansoriopterygids, they have shown similar skeletal and integumentary
      morphologies. Here we report a distinctive new Yanliao theropod species bearing
      prominent lacrimal crests, bony ornaments previously known from more basal
      theropods. It shows longer arm and leg feathers than Anchiornis and tail feathers
      with asymmetrical vanes forming a tail surface area even larger than that in
      Archaeopteryx. Nanostructures, interpreted as melanosomes, are morphologically
      similar to organized, platelet-shaped organelles that produce bright iridescent
      colours in extant birds. The new species indicates the presence of bony
      ornaments, feather colour and flight-related features consistent with proposed
      rapid character evolution and significant diversity in signalling and locomotor
      strategies near bird origins.

PMID- 29335538
TI  - Speed-related activation in the mesolimbic dopamine system during the observation
      of driver-view videos.
AB  - Despite the ubiquity and importance of speeding offenses, there has been little
      neuroscience research regarding the propensity for speeding among vehicle
      drivers. In the current study, as a first attempt, we examined the hypothesis
      that visual inputs during high-speed driving would activate the mesolimbic
      dopaminergic system that plays an important role in mediating motivational
      craving. To this end, we used functional magnetic resonance imaging to identify
      speed-related activation changes in mesolimbic dopaminergic regions during the
      observation of driver-view videos in two groups that differed in self-reported
      speeding propensity. Results revealed, as we expected, greater activation in the
      ventral tegmental area (VTA) in response to driver-view videos with higher speed.
      Contrary to our expectation, however, we found no significant between-group
      difference in speed-related activation changes in mesolimbic dopaminergic
      regions. Instead, an exploratory psychophysiological interaction analysis found
      that self-reported speeding propensity was associated with speed-related
      functional coupling between the VTA and the right intraparietal sulcus. Further
      validation of our hypothesis will require future studies examining associations
      between speed-related activation in the mesolimbic dopaminergic system and
      individual differences in speeding propensity, using a more reliable measure of
      actual speeding propensity in real traffic.

PMID- 29335540
TI  - Publisher Correction: Acoustic allometry revisited: morphological determinants of
      fundamental frequency in primate vocal production.
AB  - A correction to this article has been published and is linked from the HTML
      version of this paper. The error has not been fixed in the paper.

PMID- 29335539
TI  - Brain activity patterns in high-throughput electrophysiology screen predict both
      drug efficacies and side effects.
AB  - Neurological drugs are often associated with serious side effects, yet drug
      screens typically focus only on efficacy. We demonstrate a novel paradigm
      utilizing high-throughput in vivo electrophysiology and brain activity patterns
      (BAPs). A platform with high sensitivity records local field potentials (LFPs)
      simultaneously from many zebrafish larvae over extended periods. We show that
      BAPs from larvae experiencing epileptic seizures or drug-induced side effects
      have substantially reduced complexity (entropy), similar to reduced LFP
      complexity observed in Parkinson's disease. To determine whether drugs that
      enhance BAP complexity produces positive outcomes, we used light pulses to
      trigger seizures in a model of Dravet syndrome, an intractable genetic epilepsy.
      The highest-ranked compounds identified by BAP analysis exhibit far greater anti
      seizure efficacy and fewer side effects during subsequent in-depth behavioral
      assessment. This high correlation with behavioral outcomes illustrates the power
      of brain activity pattern-based screens and identifies novel therapeutic
      candidates with minimal side effects.

PMID- 29335541
TI  - Modulation of UVB-induced Carcinogenesis by Activation of Alternative DNA Repair
      Pathways.
AB  - The molecular basis for ultraviolet (UV) light-induced nonmelanoma and melanoma
      skin cancers centers on cumulative genomic instability caused by inefficient DNA
      repair of dipyrimidine photoproducts. Inefficient DNA repair and subsequent
      translesion replication past these DNA lesions generate distinct molecular
      signatures of tandem CC to TT and C to T transitions at dipyrimidine sites. Since
      previous efforts to develop experimental strategies to enhance the repair
      capacity of basal keratinocytes have been limited, we have engineered the N
      terminally truncated form (Delta228) UV endonuclease (UVDE) from
      Schizosaccharomyces pombe to include a TAT cell-penetrating peptide sequence with
      or without a nuclear localization signal (NLS): UVDE-TAT and UVDE-NLS-TAT.
      Further, a NLS was engineered onto a pyrimidine dimer glycosylase from Paramecium
      bursaria chlorella virus-1 (cv-pdg-NLS). Purified enzymes were encapsulated into
      liposomes and topically delivered to the dorsal surface of SKH1 hairless mice in
      a UVB-induced carcinogenesis study. Total tumor burden was significantly reduced
      in mice receiving either UVDE-TAT or UVDE-NLS-TAT versus control empty liposomes
      and time to death was significantly reduced with the UVDE-NLS-TAT. These data
      suggest that efficient delivery of exogenous enzymes for the initiation of repair
      of UVB-induced DNA damage may protect from UVB induction of squamous and basal
      cell carcinomas.

PMID- 29335543
TI  - Genetics of lipid metabolism in prostate cancer.

PMID- 29335542
TI  - Compartmentalized activities of the pyruvate dehydrogenase complex sustain
      lipogenesis in prostate cancer.
AB  - The mechanisms by which mitochondrial metabolism supports cancer anabolism remain
      unclear. Here, we found that genetic and pharmacological inactivation of pyruvate
      dehydrogenase A1 (PDHA1), a subunit of the pyruvate dehydrogenase complex (PDC),
      inhibits prostate cancer development in mouse and human xenograft tumor models by
      affecting lipid biosynthesis. Mechanistically, we show that in prostate cancer,
      PDC localizes in both the mitochondria and the nucleus. Whereas nuclear PDC
      controls the expression of sterol regulatory element-binding transcription factor
      (SREBF)-target genes by mediating histone acetylation, mitochondrial PDC provides
      cytosolic citrate for lipid synthesis in a coordinated manner, thereby sustaining
      anabolism. Additionally, we found that PDHA1 and the PDC activator pyruvate
      dehydrogenase phosphatase 1 (PDP1) are frequently amplified and overexpressed at
      both the gene and protein levels in prostate tumors. Together, these findings
      demonstrate that both mitochondrial and nuclear PDC sustain prostate
      tumorigenesis by controlling lipid biosynthesis, thus suggesting this complex as
      a potential target for cancer therapy.

PMID- 29335544
TI  - Transposon-derived small RNAs triggered by miR845 mediate genome dosage response
      in Arabidopsis.
AB  - Chromosome dosage has substantial effects on reproductive isolation and
      speciation in both plants and animals, but the underlying mechanisms are largely
      obscure 1 . Transposable elements in animals can regulate hybridity through
      maternal small RNA 2 , whereas small RNAs in plants have been postulated to
      regulate dosage response via neighboring imprinted genes3,4. Here we show that a
      highly conserved microRNA in plants, miR845, targets the tRNAMet primer-binding
      site (PBS) of long terminal repeat (LTR) retrotransposons in Arabidopsis pollen,
      and triggers the accumulation of 21-22-nucleotide (nt) small RNAs in a dose
      dependent fashion via RNA polymerase IV. We show that these epigenetically
      activated small interfering RNAs (easiRNAs) mediate hybridization barriers
      between diploid seed parents and tetraploid pollen parents (the 'triploid
      block'), and that natural variation for miR845 may account for 'endosperm
      balance' allowing the formation of triploid seeds. Targeting of the PBS with
      small RNA is a common mechanism for transposon control in mammals and plants, and
      provides a uniquely sensitive means to monitor chromosome dosage and imprinting
      in the developing seed.

PMID- 29335545
TI  - An aberrant SREBP-dependent lipogenic program promotes metastatic prostate
      cancer.
AB  - Lipids, either endogenously synthesized or exogenous, have been linked to human
      cancer. Here we found that PML is frequently co-deleted with PTEN in metastatic
      human prostate cancer (CaP). We demonstrated that conditional inactivation of Pml
      in the mouse prostate morphs indolent Pten-null tumors into lethal metastatic
      disease. We identified MAPK reactivation, subsequent hyperactivation of an
      aberrant SREBP prometastatic lipogenic program, and a distinctive lipidomic
      profile as key characteristic features of metastatic Pml and Pten double-null
      CaP. Furthermore, targeting SREBP in vivo by fatostatin blocked both tumor growth
      and distant metastasis. Importantly, a high-fat diet (HFD) induced lipid
      accumulation in prostate tumors and was sufficient to drive metastasis in a
      nonmetastatic Pten-null mouse model of CaP, and an SREBP signature was highly
      enriched in metastatic human CaP. Thus, our findings uncover a prometastatic
      lipogenic program and lend direct genetic and experimental support to the notion
      that a Western HFD can promote metastasis.

PMID- 29335547
TI  - Pan-genome analysis highlights the extent of genomic variation in cultivated and
      wild rice.
AB  - The rich genetic diversity in Oryza sativa and Oryza rufipogon serves as the main
      sources in rice breeding. Large-scale resequencing has been undertaken to
      discover allelic variants in rice, but much of the information for genetic
      variation is often lost by direct mapping of short sequence reads onto the O.
      sativa japonica Nipponbare reference genome. Here we constructed a pan-genome
      dataset of the O. sativa-O. rufipogon species complex through deep sequencing and
      de novo assembly of 66 divergent accessions. Intergenomic comparisons identified
      23 million sequence variants in the rice genome. This catalog of sequence
      variations includes many known quantitative trait nucleotides and will be helpful
      in pinpointing new causal variants that underlie complex traits. In particular,
      we systemically investigated the whole set of coding genes using this pan-genome
      data, which revealed extensive presence and absence of variation among rice
      accessions. This pan-genome resource will further promote evolutionary and
      functional studies in rice.

PMID- 29335546
TI  - Transcription factors orchestrate dynamic interplay between genome topology and
      gene regulation during cell reprogramming.
AB  - Chromosomal architecture is known to influence gene expression, yet its role in
      controlling cell fate remains poorly understood. Reprogramming of somatic cells
      into pluripotent stem cells (PSCs) by the transcription factors (TFs) OCT4, SOX2,
      KLF4 and MYC offers an opportunity to address this question but is severely
      limited by the low proportion of responding cells. We have recently developed a
      highly efficient reprogramming protocol that synchronously converts somatic into
      pluripotent stem cells. Here, we used this system to integrate time-resolved
      changes in genome topology with gene expression, TF binding and chromatin-state
      dynamics. The results showed that TFs drive topological genome reorganization at
      multiple architectural levels, often before changes in gene expression. Removal
      of locus-specific topological barriers can explain why pluripotency genes are
      activated sequentially, instead of simultaneously, during reprogramming.
      Together, our results implicate genome topology as an instructive force for
      implementing transcriptional programs and cell fate in mammals.

PMID- 29335548
TI  - Paternal easiRNAs regulate parental genome dosage in Arabidopsis.
AB  - The regulation of parental genome dosage is of fundamental importance in animals
      and plants, as exemplified by X-chromosome inactivation and dosage compensation.
      The 'triploid block' is a classic example of dosage regulation in plants that
      establishes a reproductive barrier between species differing in chromosome
      number1,2. This barrier acts in the embryo-nourishing endosperm tissue and
      induces the abortion of hybrid seeds through a yet unknown mechanism 3 . Here we
      show that depletion of paternal epigenetically activated small interfering RNAs
      (easiRNAs) bypasses the triploid block in response to increased paternal ploidy
      in Arabidopsis thaliana. Paternal loss of the plant-specific RNA polymerase IV
      suppressed easiRNA formation and rescued triploid seeds by restoring small-RNA
      directed DNA methylation at transposable elements (TEs), correlating with reduced
      expression of paternally expressed imprinted genes (PEGs). Our data suggest that
      easiRNAs form a quantitative signal for paternal chromosome number and that their
      balanced dosage is required for post-fertilization genome stability and seed
      viability.

PMID- 29335549
TI  - Reconstructing an African haploid genome from the 18th century.
AB  - A genome is a mosaic of chromosome fragments from ancestors who existed some
      arbitrary number of generations earlier. Here, we reconstruct the genome of Hans
      Jonatan (HJ), born in the Caribbean in 1784 to an enslaved African mother and
      European father. HJ migrated to Iceland in 1802, married and had two children. We
      genotyped 182 of his 788 descendants using single-nucleotide polymorphism (SNP)
      chips and whole-genome sequenced (WGS) 20 of them. Using these data, we
      reconstructed 38% of HJ's maternal genome and inferred that his mother was from
      the region spanned by Benin, Nigeria and Cameroon.

PMID- 29335550
TI  - The PEG-responding desiccome of the alder microsymbiont Frankia alni.
AB  - Actinorhizal plants are ecologically and economically important. Symbiosis with
      nitrogen-fixing bacteria allows these woody dicotyledonous plants to colonise
      soils under nitrogen deficiency, water-stress or other extreme conditions.
      However, proteins involved in xerotolerance of symbiotic microorganisms have yet
      to be identified. Here we characterise the polyethylene glycol (PEG)-responding
      desiccome from the most geographically widespread Gram-positive nitrogen-fixing
      plant symbiont, Frankia alni, by next-generation proteomics, taking advantage of
      a Q-Exactive HF tandem mass spectrometer equipped with an ultra-high-field
      Orbitrap analyser. A total of 2,052 proteins were detected and quantified. Under
      osmotic stress, PEG-grown F. alni cells increased the abundance of envelope
      associated proteins like ABC transporters, mechano-sensitive ion channels and
      Clustered Regularly Interspaced Short Palindromic Repeats CRISPR-associated (cas)
      components. Conjointly, dispensable pathways, like nitrogen fixation, aerobic
      respiration and homologous recombination, were markedly down-regulated. Molecular
      modelling and docking simulations suggested that the PEG is acting on Frankia
      partly by filling the inner part of an up-regulated osmotic-stress large
      conductance mechanosensitive channel.

PMID- 29335552
TI  - A pathway for biological methane production using bacterial iron-only
      nitrogenase.
AB  - Methane (CH4) is a potent greenhouse gas that is released from fossil fuels and
      is also produced by microbial activity, with at least one billion tonnes of CH4
      being formed and consumed by microorganisms in a single year 1 . Complex
      methanogenesis pathways used by archaea are the main route for bioconversion of
      carbon dioxide (CO2) to CH4 in nature2-4. Here, we report that wild-type iron
      iron (Fe-only) nitrogenase from the bacterium Rhodopseudomonas palustris reduces
      CO2 simultaneously with nitrogen gas (N2) and protons to yield CH4, ammonia (NH3)
      and hydrogen gas (H2) in a single enzymatic step. The amount of CH4 produced by
      purified Fe-only nitrogenase was low compared to its other products, but CH4
      production by this enzyme in R. palustris was sufficient to support the growth of
      an obligate CH4-utilizing Methylomonas strain when the two microorganisms were
      grown in co-culture, with oxygen (O2) added at intervals. Other nitrogen-fixing
      bacteria that we tested also formed CH4 when expressing Fe-only nitrogenase,
      suggesting that this is a general property of this enzyme. The genomes of 9% of
      diverse nitrogen-fixing microorganisms from a range of environments encode Fe
      only nitrogenase. Our data suggest that active Fe-only nitrogenase, present in
      diverse microorganisms, contributes CH4 that could shape microbial community
      interactions.

PMID- 29335553
TI  - Mutations in ppe38 block PE_PGRS secretion and increase virulence of
      Mycobacterium tuberculosis.
AB  - Mycobacterium tuberculosis requires a large number of secreted and exported
      proteins for its virulence, immune modulation and nutrient uptake. Most of these
      proteins are transported by the different type VII secretion systems1,2. The most
      recently evolved type VII secretion system, ESX-5, secretes dozens of substrates
      belonging to the PE and PPE families, which are named for conserved proline and
      glutamic acid residues close to the amino terminus3,4. However, the role of these
      proteins remains largely elusive 1 . Here, we show that mutations of ppe38
      completely block the secretion of two large subsets of ESX-5 substrates, that is,
      PPE-MPTR and PE_PGRS, together comprising >80 proteins. Importantly,
      hypervirulent clinical M. tuberculosis strains of the Beijing lineage have such a
      mutation and a concomitant loss of secretion 5 . Restoration of PPE38-dependent
      secretion partially reverted the hypervirulence phenotype of a Beijing strain,
      and deletion of ppe38 in moderately virulent M. tuberculosis increased virulence.
      This indicates that these ESX-5 substrates have an important role in virulence
      attenuation. Phylogenetic analysis revealed that deletion of ppe38 occurred at
      the branching point of the 'modern' Beijing sublineage and is shared by Beijing
      outbreak strains worldwide, suggesting that this deletion may have contributed to
      their success and global distribution6,7.

PMID- 29335551
TI  - Tumor-derived exosomal miR-1247-3p induces cancer-associated fibroblast
      activation to foster lung metastasis of liver cancer.
AB  - The communication between tumor-derived elements and stroma in the metastatic
      niche has a critical role in facilitating cancer metastasis. Yet, the mechanisms
      tumor cells use to control metastatic niche formation are not fully understood.
      Here we report that in the lung metastatic niche, high-metastatic hepatocellular
      carcinoma (HCC) cells exhibit a greater capacity to convert normal fibroblasts to
      cancer-associated fibroblasts (CAFs) than low-metastatic HCC cells. We show high
      metastatic HCC cells secrete exosomal miR-1247-3p that directly targets B4GALT3,
      leading to activation of beta1-integrin-NF-kappaB signaling in fibroblasts.
      Activated CAFs further promote cancer progression by secreting pro-inflammatory
      cytokines, including IL-6 and IL-8. Clinical data show high serum exosomal miR
      1247-3p levels correlate with lung metastasis in HCC patients. These results
      demonstrate intercellular crosstalk between tumor cells and fibroblasts is
      mediated by tumor-derived exosomes that control lung metastasis of HCC, providing
      potential targets for prevention and treatment of cancer metastasis.

PMID- 29335555
TI  - Metatranscriptome of human faecal microbial communities in a cohort of adult men.
AB  - The gut microbiome is intimately related to human health, but it is not yet known
      which functional activities are driven by specific microorganisms' ecological
      configurations or transcription. We report a large-scale investigation of 372
      human faecal metatranscriptomes and 929 metagenomes from a subset of 308 men in
      the Health Professionals Follow-Up Study. We identified a metatranscriptomic
      'core' universally transcribed over time and across participants, often by
      different microorganisms. In contrast to the housekeeping functions enriched in
      this core, a 'variable' metatranscriptome included specialized pathways that were
      differentially expressed both across participants and among microorganisms.
      Finally, longitudinal metagenomic profiles allowed ecological interaction network
      reconstruction, which remained stable over the six-month timespan, as did strain
      tracking within and between participants. These results provide an initial
      characterization of human faecal microbial ecology into core, subject-specific,
      microorganism-specific and temporally variable transcription, and they
      differentiate metagenomically versus metatranscriptomically informative aspects
      of the human faecal microbiome.

PMID- 29335554
TI  - Stability of the human faecal microbiome in a cohort of adult men.
AB  - Characterizing the stability of the gut microbiome is important to exploit it as
      a therapeutic target and diagnostic biomarker. We metagenomically and
      metatranscriptomically sequenced the faecal microbiomes of 308 participants in
      the Health Professionals Follow-Up Study. Participants provided four stool
      samples-one pair collected 24-72 h apart and a second pair ~6 months later.
      Within-person taxonomic and functional variation was consistently lower than
      between-person variation over time. In contrast, metatranscriptomic profiles were
      comparably variable within and between subjects due to higher within-subject
      longitudinal variation. Metagenomic instability accounted for ~74% of
      corresponding metatranscriptomic instability. The rest was probably attributable
      to sources such as regulation. Among the pathways that were differentially
      regulated, most were consistently over- or under-transcribed at each time point.
      Together, these results suggest that a single measurement of the faecal
      microbiome can provide long-term information regarding organismal composition and
      functional potential, but repeated or short-term measures may be necessary for
      dynamic features identified by metatranscriptomics.

PMID- 29335556
TI  - Thermodynamic insight into stimuli-responsive behaviour of soft porous crystals.
AB  - Knowledge of the thermodynamic potential in terms of the independent variables
      allows to characterize the macroscopic state of the system. However, in practice,
      it is difficult to access this potential experimentally due to irreversible
      transitions that occur between equilibrium states. A showcase example of sudden
      transitions between (meta)stable equilibrium states is observed for soft porous
      crystals possessing a network with long-range structural order, which can
      transform between various states upon external stimuli such as pressure,
      temperature and guest adsorption. Such phase transformations are typically
      characterized by large volume changes and may be followed experimentally by
      monitoring the volume change in terms of certain external triggers. Herein, we
      present a generalized thermodynamic approach to construct the underlying
      Helmholtz free energy as a function of the state variables that governs the
      observed behaviour based on microscopic simulations. This concept allows a unique
      identification of the conditions under which a material becomes flexible.

PMID- 29335557
TI  - A framework for quantifying the relationship between intensity and severity of
      impact of disturbance across types of events and species.
AB  - Understanding the impacts of natural disturbances on wildlife populations is a
      central task for ecologists; in general, the severity of impact of a disturbance
      (e.g., the resulting degree of population decline) is likely to depend primarily
      on the disturbance intensity (i.e., strength of forcing), type of disturbance,
      and species vulnerability. However, differences among disturbance events in the
      physical units of forcing and interspecific differences in the temporal
      variability of population size under normal (non-disturbance) conditions hinder
      comprehensive analysis of disturbance severity. Here, we propose new measures of
      disturbance intensity and severity, both represented by the return periods. We
      use a meta-analysis to describe the severity-intensity relationship across
      various disturbance types and species. The severity and the range of its 95%
      confidential interval increased exponentially with increasing intensity. This
      nonlinear relationship suggests that physically intense events may have a
      catastrophic impact, but their severity cannot be extrapolated from the severity
      intensity relationship for weak, frequent disturbance events. The framework we
      propose may help to clarify the influence of event types and species traits on
      the severity-intensity relationship, as well as to improve our ability to predict
      the ecological consequences of various disturbance events of unexperienced
      intensity.

PMID- 29335558
TI  - Strongly exchange-coupled and surface-state-modulated magnetization dynamics in
      Bi2Se3/yttrium iron garnet heterostructures.
AB  - Harnessing the spin-momentum locking of topological surface states in conjunction
      with magnetic materials is the first step to realize novel topological insulator
      based devices. Here, we report strong interfacial coupling in Bi2Se3/yttrium iron
      garnet (YIG) bilayers manifested as large interfacial in-plane magnetic
      anisotropy (IMA) and enhancement of damping probed by ferromagnetic resonance.
      The interfacial IMA and damping enhancement reaches a maximum when the Bi2Se3
      film approaches its two-dimensional limit, indicating that topological surface
      states play an important role in the magnetization dynamics of YIG. Temperature
      dependent ferromagnetic resonance of Bi2Se3/YIG reveals signatures of the
      magnetic proximity effect of TC as high as 180 K, an emerging low-temperature
      perpendicular magnetic anisotropy competing the high-temperature IMA, and an
      increasing exchange effective field of YIG steadily increasing toward low
      temperature. Our study sheds light on the effects of topological insulators on
      magnetization dynamics, essential for the development of topological insulator
      based spintronic devices.

PMID- 29335559
TI  - Publisher Correction: Fusion guide RNAs for orthogonal gene manipulation with
      Cas9 and Cpf1.
AB  - The originally published version of this Article contained an error in the
      spelling of the author Da-eun Kim, which was incorrectly given as Da-Eun Kim.
      Furthermore, in Figure 1a, the Cas9 protein was positioned incorrectly during
      typesetting. These errors have now been corrected in both the PDF and HTML
      versions of the Article.

PMID- 29335560
TI  - Ligands with 1,10-phenanthroline scaffold for highly regioselective iron
      catalyzed alkene hydrosilylation.
AB  - Transition-metal-catalyzed alkene hydrosilylation is one of the most important
      homogeneous catalytic reactions, and the development of methods that use base
      metals, especially iron, as catalysts for this transformation is a growing area
      of research. However, the limited number of ligand scaffolds applicable for base
      metal-catalyzed alkene hydrosilylation has seriously hindered advances in this
      area. Herein, we report the use of 1,10-phenanthroline ligands in base-metal
      catalysts for alkene hydrosilylation. In particular, iron catalysts with 2,9
      diaryl-1,10-phenanthroline ligands exhibit unexpected reactivity and selectivity
      for hydrosilylation of alkenes, including unique benzylic selectivity with
      internal alkenes, Markovnikov selectivity with terminal styrenes and 1,3-dienes,
      and excellent activity toward aliphatic terminal alkenes. According to the
      mechanistic studies, the unusual benzylic selectivity of this hydrosilylation
      initiates from pi-pi interaction between the phenyl of the alkene and the
      phenanthroline of the ligand. This ligand scaffold and its unique catalytic model
      will open possibilities for base-metal-catalyzed hydrosilylation reactions.

PMID- 29335561
TI  - Sub-angstrom cryo-EM structure of a prion protofibril reveals a polar clasp.
AB  - The atomic structure of the infectious, protease-resistant, beta-sheet-rich and
      fibrillar mammalian prion remains unknown. Through the cryo-EM method MicroED, we
      reveal the sub-angstrom-resolution structure of a protofibril formed by a wild
      type segment from the beta2-alpha2 loop of the bank vole prion protein. The
      structure of this protofibril reveals a stabilizing network of hydrogen bonds
      that link polar zippers within a sheet, producing motifs we have named 'polar
      clasps'.

PMID- 29335562
TI  - Cryo-EM structure of the exocyst complex.
AB  - The exocyst is an evolutionarily conserved octameric protein complex that
      mediates the tethering of post-Golgi secretory vesicles to the plasma membrane
      during exocytosis and is implicated in many cellular processes such as cell
      polarization, cytokinesis, ciliogenesis and tumor invasion. Using cryo-EM and
      chemical cross-linking MS (CXMS), we solved the structure of the Saccharomyces
      cerevisiae exocyst complex at an average resolution of 4.4 A. Our model revealed
      the architecture of the exocyst and led to the identification of the helical
      bundles that mediate the assembly of the complex at its core. Sequence analysis
      suggests that these regions are evolutionarily conserved across eukaryotic
      systems. Additional cell biological data suggest a mechanism for exocyst assembly
      that leads to vesicle tethering at the plasma membrane.

PMID- 29335564
TI  - Electrical control of charged carriers and excitons in atomically thin materials.
AB  - Electrical confinement and manipulation of charge carriers in semiconducting
      nanostructures are essential for realizing functional quantum electronic devices1
      3. The unique band structure4-7 of atomically thin transition metal
      dichalcogenides (TMDs) offers a new route towards realizing novel 2D quantum
      electronic devices, such as valleytronic devices and valley-spin qubits 8 . 2D
      TMDs also provide a platform for novel quantum optoelectronic devices9-11 due to
      their large exciton binding energy12,13. However, controlled confinement and
      manipulation of electronic and excitonic excitations in TMD nanostructures have
      been technically challenging due to the prevailing disorder in the material,
      preventing accurate experimental control of local confinement and tunnel
      couplings14-16. Here we demonstrate a novel method for creating high-quality
      heterostructures composed of atomically thin materials that allows for efficient
      electrical control of excitations. Specifically, we demonstrate quantum transport
      in the gate-defined, quantum-confined region, observing spin-valley locked
      quantized conductance in quantum point contacts. We also realize gate-controlled
      Coulomb blockade associated with confinement of electrons and demonstrate
      electrical control over charged excitons with tunable local confinement
      potentials and tunnel couplings. Our work provides a basis for novel quantum opto
      electronic devices based on manipulation of charged carriers and excitons.

PMID- 29335563
TI  - Visualization and analysis of non-covalent contacts using the Protein Contacts
      Atlas.
AB  - Visualizations of biomolecular structures empower us to gain insights into
      biological functions, generate testable hypotheses, and communicate biological
      concepts. Typical visualizations (such as ball and stick) primarily depict
      covalent bonds. In contrast, non-covalent contacts between atoms, which govern
      normal physiology, pathogenesis, and drug action, are seldom visualized. We
      present the Protein Contacts Atlas, an interactive resource of non-covalent
      contacts from over 100,000 PDB crystal structures. We developed multiple
      representations for visualization and analysis of non-covalent contacts at
      different scales of organization: atoms, residues, secondary structure, subunits,
      and entire complexes. The Protein Contacts Atlas enables researchers from
      different disciplines to investigate diverse questions in the framework of non
      covalent contacts, including the interpretation of allostery, disease mutations
      and polymorphisms, by exploring individual subunits, interfaces, and protein
      ligand contacts and by mapping external information. The Protein Contacts Atlas
      is available at http://www.mrc-lmb.cam.ac.uk/pca/ and also through PDBe.

PMID- 29335565
TI  - Ballistic Majorana nanowire devices.
AB  - Majorana modes are zero-energy excitations of a topological superconductor that
      exhibit non-Abelian statistics1-3. Following proposals for their detection in a
      semiconductor nanowire coupled to an s-wave superconductor4,5, several tunnelling
      experiments reported characteristic Majorana signatures6-11. Reducing disorder
      has been a prime challenge for these experiments because disorder can mimic the
      zero-energy signatures of Majoranas12-16, and renders the topological properties
      inaccessible17-20. Here, we show characteristic Majorana signatures in InSb
      nanowire devices exhibiting clear ballistic transport properties. Application of
      a magnetic field and spatial control of carrier density using local gates
      generates a zero bias peak that is rigid over a large region in the parameter
      space of chemical potential, Zeeman energy and tunnel barrier potential. The
      reduction of disorder allows us to resolve separate regions in the parameter
      space with and without a zero bias peak, indicating topologically distinct
      phases. These observations are consistent with the Majorana theory in a ballistic
      system 21 , and exclude the known alternative explanations that invoke disorder12
      16 or a nonuniform chemical potential22,23.

PMID- 29335566
TI  - Tunable confinement of charges and excitations.

PMID- 29335567
TI  - Metagenomic analysis of microbial communities yields insight into impacts of
      nanoparticle design.
AB  - Next-generation DNA sequencing and metagenomic analysis provide powerful tools
      for the environmentally friendly design of nanoparticles. Herein we demonstrate
      this approach using a model community of environmental microbes (that is,
      wastewater-activated sludge) dosed with gold nanoparticles of varying surface
      coatings and morphologies. Metagenomic analysis was highly sensitive in detecting
      the microbial community response to gold nanospheres and nanorods with either
      cetyltrimethylammonium bromide or polyacrylic acid surface coatings. We observed
      that the gold-nanoparticle morphology imposes a stronger force in shaping the
      microbial community structure than does the surface coating. Trends were
      consistent in terms of the compositions of both taxonomic and functional genes,
      which include antibiotic resistance genes, metal resistance genes and gene
      transfer elements associated with cell stress that are relevant to public health.
      Given that nanoparticle morphology remained constant, the potential influence of
      gold dissolution was minimal. Surface coating governed the nanoparticle
      partitioning between the bioparticulate and aqueous phases.

PMID- 29335568
TI  - Strain distributions and their influence on electronic structures of WSe2-MoS2
      laterally strained heterojunctions.
AB  - Monolayer transition metal dichalcogenide heterojunctions, including vertical and
      lateral p-n junctions, have attracted considerable attention due to their
      potential applications in electronics and optoelectronics. Lattice-misfit strain
      in atomically abrupt lateral heterojunctions, such as WSe2-MoS2, offers a new
      band-engineering strategy for tailoring their electronic properties. However,
      this approach requires an understanding of the strain distribution and its effect
      on band alignment. Here, we study a WSe2-MoS2 lateral heterojunction using
      scanning tunnelling microscopy and image its moire pattern to map the full two
      dimensional strain tensor with high spatial resolution. Using scanning tunnelling
      spectroscopy, we measure both the strain and the band alignment of the WSe2-MoS2
      lateral heterojunction. We find that the misfit strain induces type II to type I
      band alignment transformation. Scanning transmission electron microscopy reveals
      the dislocations at the interface that partially relieve the strain. Finally, we
      observe a distinctive electronic structure at the interface due to hetero
      bonding.

PMID- 29335570
TI  - Machine learning for tracking illegal wildlife trade on social media.

PMID- 29335569
TI  - Apparent shift in long-range motion trajectory by local pattern orientation.
AB  - The present study shows that the apparent direction of a moving pattern is
      systematically affected by its orientation. We found that the perceived direction
      of motion of a single Gabor grating changing position in discrete steps
      interleaved by blank inter-stimulus interval (ISI) is biased toward the
      orientation of the grating. This orientation-induced motion shift peaks for
      grating orientations ~+/-15 deg away from the physical motion trajectory and was
      profound for relatively short distances. Orientation adaptation revealed that the
      directional shift is determined by the apparent -not the physical -orientation of
      the grating, and a subsequent experiment demonstrated that directional shift is
      also influenced by the orientation of the contrast-defined stimulus envelope.
      Results provide further evidence that the apparent trajectory of a motion
      stimulus is determined by interactions between motion and pattern information at
      relatively high levels of visual processing.

PMID- 29335571
TI  - Biodiversity conservation should be a core value of China's Belt and Road
      Initiative.

PMID- 29335572
TI  - Variation and constraints in hybrid genome formation.
AB  - Hybridization is an important source of variation; it transfers adaptive genetic
      variation across species boundaries and generates new species. Yet, the limits to
      viable hybrid genome formation are poorly understood. Here we investigated to
      what extent hybrid genomes are free to evolve by sequencing the genomes of four
      island populations of the homoploid hybrid Italian sparrow Passer italiae. We
      report that a variety of novel and fully functional hybrid genomic combinations
      are likely to have arisen independently on Crete, Corsica, Sicily and Malta, with
      differentiation in candidate genes for beak shape and plumage colour. However,
      certain genomic regions are invariably inherited from the same parent species,
      limiting variation. These regions are over-represented on the Z chromosome and
      harbour candidate incompatibility loci, including DNA-repair and mitonuclear
      genes. These gene classes may contribute to the general reduction of
      introgression on sex chromosomes. This study demonstrates that hybrid genomes may
      vary, and identifies new candidate reproductive isolation genes.

PMID- 29335573
TI  - Australia's mammal fauna requires a strategic and enhanced network of predator
      free havens.

PMID- 29335574
TI  - Sexual antagonism and the instability of environmental sex determination.
AB  - The sex of an organism can be determined by its genetics or its early
      environment. Across the animal kingdom, genetic sex determination (GSD) is far
      more common than environmental sex determination (ESD). Here, we propose an
      explanation for this pattern: the coupling of genes that bias offspring sex
      ratios towards one sex with genes that are beneficial in that sex but costly in
      the other. Gradual strengthening of the sex-specific tendency of this association
      eventuates in a neo-sex chromosome; that is, GSD. Our model predicts to which
      system of heterogamety ESD will evolve when nesting behaviour is an important
      determinant of brood sex ratios. It explains the puzzling observation in some GSD
      species of sex reversal induced by extreme environments. The model also suggests
      an approach to discovering sex-determining genes in ESD species.

PMID- 29335576
TI  - Ancient balancing selection on heterocyst function in a cosmopolitan
      cyanobacterium.
AB  - The conventional view of bacterial adaptation emphasizes the importance of
      rapidly evolved changes that are highly repeatable in response to similar
      environments and subject to loss in the absence of selection. Consequently,
      genetic variation is not expected to persist over long time scales for these
      organisms. Here, we show that a geographically widespread gene content
      polymorphism has surprisingly been maintained for tens of millions of years of
      diversification of the multicellular cyanobacterium Fischerella thermalis. The
      polymorphism affects gas permeability of the heterocyst-the oxygen-sensitive,
      nitrogen-fixing cell produced by these bacteria-and spatial variation in
      temperature favours alternative alleles due to thermodynamic effects on both
      heterocyst function and organism fitness at physiological temperature extremes.
      Whether or not ancient balancing selection plays a generally important role in
      the maintenance of microbial diversity remains to be investigated.

PMID- 29335575
TI  - Genotypic variability enhances the reproducibility of an ecological study.
AB  - Many scientific disciplines are currently experiencing a 'reproducibility crisis'
      because numerous scientific findings cannot be repeated consistently. A novel but
      controversial hypothesis postulates that stringent levels of environmental and
      biotic standardization in experimental studies reduce reproducibility by
      amplifying the impacts of laboratory-specific environmental factors not accounted
      for in study designs. A corollary to this hypothesis is that a deliberate
      introduction of controlled systematic variability (CSV) in experimental designs
      may lead to increased reproducibility. To test this hypothesis, we had 14
      European laboratories run a simple microcosm experiment using grass (Brachypodium
      distachyon L.) monocultures and grass and legume (Medicago truncatula Gaertn.)
      mixtures. Each laboratory introduced environmental and genotypic CSV within and
      among replicated microcosms established in either growth chambers (with stringent
      control of environmental conditions) or glasshouses (with more variable
      environmental conditions). The introduction of genotypic CSV led to 18% lower
      among-laboratory variability in growth chambers, indicating increased
      reproducibility, but had no significant effect in glasshouses where
      reproducibility was generally lower. Environmental CSV had little effect on
      reproducibility. Although there are multiple causes for the 'reproducibility
      crisis', deliberately including genetic variability may be a simple solution for
      increasing the reproducibility of ecological studies performed under stringently
      controlled environmental conditions.

PMID- 29335577
TI  - Salmonella enterica genomes from victims of a major sixteenth-century epidemic in
      Mexico.
AB  - Indigenous populations of the Americas experienced high mortality rates during
      the early contact period as a result of infectious diseases, many of which were
      introduced by Europeans. Most of the pathogenic agents that caused these
      outbreaks remain unknown. Through the introduction of a new metagenomic analysis
      tool called MALT, applied here to search for traces of ancient pathogen DNA, we
      were able to identify Salmonella enterica in individuals buried in an early
      contact era epidemic cemetery at Teposcolula-Yucundaa, Oaxaca in southern Mexico.
      This cemetery is linked, based on historical and archaeological evidence, to the
      1545-1550 CE epidemic that affected large parts of Mexico. Locally, this epidemic
      was known as 'cocoliztli', the pathogenic cause of which has been debated for
      more than a century. Here, we present genome-wide data from ten individuals for
      Salmonella enterica subsp. enterica serovar Paratyphi C, a bacterial cause of
      enteric fever. We propose that S. Paratyphi C be considered a strong candidate
      for the epidemic population decline during the 1545 cocoliztli outbreak at
      Teposcolula-Yucundaa.

PMID- 29335578
TI  - Author Correction: The rise and fall of the Old World savannah fauna and the
      origins of the African savannah biome.
AB  - In the version of this Article originally published, each of the five panels in
      Fig. 5 incorrectly contained a black diagonal line across the plot. This has now
      been corrected.

PMID- 29335579
TI  - The effects of Antibody Engineering CH and CL in Trastuzumab and Pertuzumab
      recombinant models: Impact on antibody production and antigen-binding.
AB  - Current therapeutic antibodies such as Trastuzumab, are typically of the blood
      circulatory IgG1 class (Ckappa/ CHgamma1). Due to the binding to Her2 also
      present on normal cell surfaces, side effects such as cardiac failure can
      sometimes be associated with such targeted therapy. Using antibody isotype
      swapping, it may be possible to reduce systemic circulation through increased
      tissue localization, thereby minimising unwanted side effects. However, the
      effects of such modifications have yet to be fully characterized, particularly
      with regards to their biophysical properties in antigen binding. To do this, we
      produced all light and heavy chain human isotypes/subtypes recombinant versions
      of Trastuzumab and Pertuzumab, and studied them with respect to recombinant
      production and Her2 binding. Our findings show that while the light chain
      constant region changes have no major effects on production or Her2 binding, some
      heavy chain isotypes, in particularly, IgM and IgD isotypes, can modulate antigen
      binding. This study thus provides the groundwork for such isotype modifications
      to be performed in the future to yield therapeutics of higher efficacy and
      efficiency.

PMID- 29335580
TI  - Widespread bone-based fluorescence in chameleons.
AB  - Fluorescence is widespread in marine organisms but uncommon in terrestrial
      tetrapods. We here show that many chameleon species have bony tubercles
      protruding from the skull that are visible through their scales, and fluoresce
      under UV light. Tubercles arising from bones of the skull displace all dermal
      layers other than a thin, transparent layer of epidermis, creating a 'window'
      onto the bone. In the genus Calumma, the number of these tubercles is sexually
      dimorphic in most species, suggesting a signalling role, and also strongly
      reflects species groups, indicating systematic value of these features. Co-option
      of the known fluorescent properties of bone has never before been shown, yet it
      is widespread in the chameleons of Madagascar and some African chameleon genera,
      particularly in those genera living in forested, humid habitats known to have a
      higher relative component of ambient UV light. The fluorescence emits with a
      maximum at around 430 nm in blue colour which contrasts well to the green and
      brown background reflectance of forest habitats. This discovery opens new avenues
      in the study of signalling among chameleons and sexual selection factors driving
      ornamentation.

PMID- 29335581
TI  - Role of hypoxia in Diffuse Large B-cell Lymphoma: Metabolic repression and
      selective translation of HK2 facilitates development of DLBCL.
AB  - Published molecular profiling studies in patients with lymphoma suggested the
      influence of hypoxia inducible factor-1 alpha (HIF1alpha) targets in prognosis of
      DLBCL. Yet, the role of hypoxia in hematological malignancies remains unclear. We
      observed that activation of HIF1alpha resulted in global translation repression
      during hypoxic stress in DLBCL. Protein translation efficiency as measured using
      35S-labeled methionine incorporation revealed a >=50% reduction in translation
      upon activation of HIF1alpha. Importantly, translation was not completely
      inhibited and expression of clinically correlated hypoxia targets such as GLUT1,
      HK2, and CYT-C was found to be refractory to translational repression under
      hypoxia in DLBCL cells. Notably, hypoxic induction of these genes was not
      observed in normal primary B-cells. Translational repression was coupled with a
      decrease in mitochondrial function. Screening of primary DLBCL patient samples
      revealed that expression of HK2, which encodes for the enzyme hexokinase 2, was
      significantly correlated with DLBCL phenotype. Genetic knockdown studies
      demonstrated that HK2 is required for promoting growth of DLBCL under hypoxic
      stress. Altogether, our findings provide strong support for the direct
      contribution of HK2 in B-cell lymphoma development and suggest that HK2 is a key
      metabolic driver of the DLBCL phenotype.

PMID- 29335582
TI  - Differential roles of NaV1.2 and NaV1.6 in regulating neuronal excitability at
      febrile temperature and distinct contributions to febrile seizures.
AB  - Dysregulation of voltage-gated sodium channels (VGSCs) is associated with
      multiple clinical disorders, including febrile seizures (FS). The contribution of
      different sodium channel subtypes to environmentally triggered seizures is not
      well understood. Here we demonstrate that somatic and axonal sodium channels
      primarily mediated through NaV1.2 and NaV1.6 subtypes, respectively, behave
      differentially at FT, and might play distinct roles in FS generation. In contrast
      to sodium channels on the main axonal trunk, somatic ones are more resistant to
      inactivation and display significantly augmented currents, faster gating rates
      and kinetics of recovery from inactivation at FT, features that promote neuronal
      excitabilities. Pharmacological inhibition of NaV1.2 by Phrixotoxin-3 (PTx3)
      suppressed FT-induced neuronal hyperexcitability in brain slice, while up
      regulation of NaV1.2 as in NaV1.6 knockout mice showed an opposite effect.
      Consistently, NaV1.6 knockout mice were more susceptible to FS, exhibiting much
      lower temperature threshold and shorter onset latency than wildtype mice. Neuron
      modeling further suggests that NaV1.2 is the major subtype mediating FT-induced
      neuronal hyperexcitability, and predicts potential outcomes of alterations in
      sodium channel subtype composition. Together, these data reveal a role of native
      NaV1.2 on neuronal excitability at FT and its important contribution to FS
      pathogenesis.

PMID- 29335583
TI  - The effect of differentiation and TGFbeta on mitochondrial respiration and
      mitochondrial enzyme abundance in cultured primary human skeletal muscle cells.
AB  - Measuring mitochondrial respiration in cultured cells is a valuable tool to
      investigate the influence of physiological and disease-related factors on
      cellular metabolism; however, the details of the experimental workflow greatly
      influence the informative value of the results. Working with primary cells and
      cell types capable of differentiation can be particularly challenging. We present
      a streamlined workflow optimised for investigation of primary human skeletal
      muscle cells. We applied the workflow to differentiated and undifferentiated
      cells and we investigated the effect of TGFbeta1 treatment. Differentiation of
      myoblasts to myotubes increased mitochondrial respiration and abundance of
      mitochondrial enzymes and mitochondrial marker proteins. Differentiation also
      induced qualitative changes in mitochondrial protein composition and respiration.
      TGFbeta1 reduced complex IV protein MTCO1 abundance in both myoblasts and
      myotubes. In myoblasts, spare electron transport system (ETS) capacity was
      reduced due to a reduction in maximal oxygen consumption. In TGFbeta1-treated
      myotubes, the reduction in spare ETS capacity is mainly a consequence of
      increased oxidative phosphorylation capacity and complex III protein UQCRC2.
      Taken together, our data shows that it is important to monitor muscle cell
      differentiation when mitochondrial function is studied. Our workflow is not only
      sensitive enough to detect physiological-sized differences, but also adequate to
      form mechanistic hypotheses.

PMID- 29335584
TI  - Genome-wide identification and characterization of SPL transcription factor
      family and their evolution and expression profiling analysis in cotton.
AB  - Plant specific transcription factors, SQUAMOSA promoter-binding protein-like
      (SPL), are involved in many biological processes. However, no systematical study
      has been reported in cotton. In this study, a total of 177 SPL genes were
      identified, including 29, 30, 59 and 59 SPLs in Gossypium arboreum, G. raimondii,
      G. barbadense, and G. hirsutum, respectively. These SPL genes were classified
      into eight phylogenetical groups. The gene structure, conserved motif, and
      clustering were highly conserved within each orthologs. Two zinc finger-like
      structures (Cys3His and Cys2HisCys) and NLS segments were existed in all GrSPLs.
      Segmental duplications play important roles in SPL family expansion, with 20
      genes involved in segmental duplications and 2 in tandem duplications, and ten
      ortholog pairs in syntenic regions between G. raimondii and A. thaliana. Several
      putative cis-elements, involved in light, stresses and phytohormones response,
      were found in the promoter regions of GhSPLs, suggesting that plant responses to
      those environmental changes may be induced through targeting SPL transcription
      factors. RNA-seq analysis shows that SPL genes were differentially expressed in
      cotton; some were highly expressed during fiber initiation and early development.
      Comparing with other plants, SPL genes show subfunctionalization, lost and/or
      gain functions in cotton during long-term domestication and evolution.

PMID- 29335586
TI  - Publisher Correction: Pelagic barite precipitation at micromolar ambient sulfate.
AB  - The original version of this Article contained an error in the barite saturation
      state equation in the fourth paragraph of the Introduction and incorrectly read
      'Omegabarite=({134Ba2+}?{SO42-})/Ksp)'. The correct version removes the
      superscript 134 next to 'Ba2+'. This error has now been corrected in both the PDF
      and HTML versions of the Article.

PMID- 29335585
TI  - Robust fabrication of thin film polyamide-TiO2 nanocomposite membranes with
      enhanced thermal stability and anti-biofouling propensity.
AB  - The development of nano-enabled composite materials has led to a paradigm shift
      in the manufacture of high-performance nanocomposite membranes with enhanced
      permeation, thermo-mechanical, and antibacterial properties. The major challenges
      to the successful incorporation of nanoparticles (NPs) to polymer films are the
      severe aggregation of the NPs and the weak compatibility of NPs with polymers.
      These two phenomena lead to the formation of non-selective voids at the interface
      of the polymer and NPs, which adversely affect the separation performance of the
      membrane. To overcome these challenges, we have developed a new method for the
      fabrication of robust TFN reverse osmosis membranes. This approach relies on the
      simultaneous synthesis and surface functionalization of TiO2 NPs in an organic
      solvent (heptane) via biphasic solvothermal reaction. The resulting stable
      suspension of the TiO2 NPs in heptane was then utilized in the interfacial (in
      situ) polymerization reaction where the NPs were entrapped within the matrix of
      the polyamide (PA) membrane. TiO2 NPs of 10 nm were effectively incorporated into
      the thin PA layer and improved the thermal stability and anti-biofouling
      properties of the resulting TFN membranes. These features make our synthesized
      membranes potential candidates for applications where the treatment of high
      temperature streams containing biomaterials is desirable.

PMID- 29335587
TI  - Bacterial and Fungal Community Composition and Functional Activity Associated
      with Lake Wetland Water Level Gradients.
AB  - The water regime is often the primary force driving the evolution of freshwater
      lakes, but how soil microbes responded to this process is far from understood.
      This study sampled wetland soils from a shallow lake that experienced water
      regime changes, Poyang Lake of China, to explore the features of bacterial and
      fungal community in response to water level changes. The soil physicochemical
      properties, T-RFLP based community structures and soil activities (including
      basal respiration, microbial biomass and enzymes) were all determined. Soil
      microbial eco-function was captured by testing the carbon metabolism with Biolog
      Ecoplate. The results showed remarkable influence of the water level gradients on
      the soil physicochemical properties, microbial community structures and soil
      activities. However, the carbon utilization profile exhibited weak connections
      with the environmental variables and microbial community structures (p > 0.05).
      The microbial activities were significantly correlated with both bacterial and
      fungal community structures. Our results also emphasized the ascendant role of
      the deterministic process in the assemblages of microbial community structures
      and functions in wetland. In conclusion, this study revealed the discrepancy
      between community structures and eco-functions in response to water level
      gradients, and a relatively stable eco-function helped to maintain the ecosystem
      function of wetland from a long-term perspective.

PMID- 29335589
TI  - Strong modulation of second-harmonic generation with very large contrast in
      semiconducting CdS via high-field domain.
AB  - Dynamic control of nonlinear signals is critical for a wide variety of
      optoelectronic applications, such as signal processing for optical computing.
      However, controlling nonlinear optical signals with large modulation strengths
      and near-perfect contrast remains a challenging problem due to intrinsic second
      order nonlinear coefficients via bulk or surface contributions. Here, via
      electrical control, we turn on and tune second-order nonlinear coefficients in
      semiconducting CdS nanobelts from zero to up to 151 pm V-1, a value higher than
      other intrinsic nonlinear coefficients in CdS. We also observe ultrahigh ON/OFF
      ratio of >104 and modulation strengths ~200% V-1 of the nonlinear signal. The
      unusual nonlinear behavior, including super-quadratic voltage and power
      dependence, is ascribed to the high-field domain, which can be further controlled
      by near-infrared optical excitation and electrical gating. The ability to
      electrically control nonlinear optical signals in nanostructures can enable
      optoelectronic devices such as optical transistors and modulators for on-chip
      integrated photonics.

PMID- 29335588
TI  - Peripheral iron levels in children with attention-deficit hyperactivity disorder:
      a systematic review and meta-analysis.
AB  - There is growing recognition that the risk of attention-deficit hyperactivity
      disorder (ADHD) in children may be influenced by micronutrient deficiencies,
      including iron. We conducted this meta-analysis to examine the association
      between ADHD and iron levels/iron deficiency (ID). We searched for the databases
      of the PubMed, ScienceDirect, Cochrane CENTRAL, and ClinicalTrials.gov up to
      August 9th, 2017. Primary outcomes were differences in peripheral iron levels in
      children with ADHD versus healthy controls (HCs) and the severity of ADHD
      symptoms in children with/without ID (Hedges' g) and the pooled adjusted odds
      ratio (OR) of the association between ADHD and ID. Overall, seventeen articles
      met the inclusion criteria. Peripheral serum ferritin levels were significantly
      lower in ADHD children (children with ADHD = 1560, HCs = 4691, Hedges' g = 
      0.246, p = 0.013), but no significant difference in serum iron or transferrin
      levels. In addition, the severity of ADHD was significantly higher in the
      children with ID than those without ID (with ID = 79, without ID = 76, Hedges' g
      = 0.888, p = 0.002), and there was a significant association between ADHD and ID
      (OR = 1.636, p = 0.031). Our results suggest that ADHD is associated with lower
      serum ferritin levels and ID. Future longitudinal studies are required to confirm
      these associations and to elucidate potential mechanisms.

PMID- 29335590
TI  - Direct observation of the effects of cellulose synthesis inhibitors using live
      cell imaging of Cellulose Synthase (CESA) in Physcomitrella patens.
AB  - Results from live cell imaging of fluorescently tagged Cellulose Synthase (CESA)
      proteins in Cellulose Synthesis Complexes (CSCs) have enhanced our understanding
      of cellulose biosynthesis, including the mechanisms of action of cellulose
      synthesis inhibitors. However, this method has been applied only in Arabidopsis
      thaliana and Brachypodium distachyon thus far. Results from freeze fracture
      electron microscopy of protonemal filaments of the moss Funaria hygrometrica
      indicate that a cellulose synthesis inhibitor, 2,6-dichlorobenzonitrile (DCB),
      fragments CSCs and clears them from the plasma membrane. This differs from
      Arabidopsis, in which DCB causes CSC accumulation in the plasma membrane and a
      different cellulose synthesis inhibitor, isoxaben, clears CSCs from the plasma
      membrane. In this study, live cell imaging of the moss Physcomitrella patens
      indicated that DCB and isoxaben have little effect on protonemal growth rates,
      and that only DCB causes tip rupture. Live cell imaging of mEGFP-PpCESA5 and
      mEGFP-PpCESA8 showed that DCB and isoxaben substantially reduced CSC movement,
      but had no measureable effect on CSC density in the plasma membrane. These
      results suggest that DCB and isoxaben have similar effects on CSC movement in P.
      patens and Arabidopsis, but have different effects on CSC intracellular
      trafficking, cell growth and cell integrity in these divergent plant lineages.

PMID- 29335591
TI  - Functionalized Sugarcane Bagasse for U(VI) Adsorption from Acid and Alkaline
      Conditions.
AB  - The highly efficient removal of uranium from mine tailings effluent, radioactive
      wastewater and enrichment from seawater is of great significance for the
      development of nuclear industry. In this work, we prepared an efficient U(VI)
      adsorbent by EDTA modified sugarcane bagasse (MESB) with a simple process. The
      prepared adsorbent preserves high adsorptive capacity for UO22+ (pH 3.0) and
      uranyl complexes, such as UO2(OH)+, (UO2)2(OH)22+ and (UO2)3(OH)5+ (pH 4.0 and pH
      5.0) and good repeatability in acidic environment. The maximum adsorption
      capacity for U(VI) at pH 3.0, 4.0 and 5.0 is 578.0, 925.9 and 1394.1 mg/g and the
      adsorption capacity loss is only 7% after five cycles. With the pH from 3.0 to
      5.0, the inhibitive effects of Na+ and K+ decreased but increased of Mg2+ and
      Ca2+. MESB also exhibits good adsorption for [UO2(CO3)3]4- at pH 8.3 from 10 mg/L
      to 3.3 MUg/L. Moreover, MESB could effectively extract U(VI) from simulated
      seawater in the presence of other metals ions. This work provided a general and
      efficient uranyl enriched material for nuclear industry.

PMID- 29335592
TI  - Differential tolerance to nickel between Dreissena polymorpha and Dreissena
      rostriformis bugensis populations.
AB  - Differential tolerance to stress is partly responsible for the heterogeneity of
      biomarker responses between populations of a sentinel species. Although currently
      used for freshwater biomonitoring, studies concerning inter-populational
      variability in tolerance to contaminants for the zebra mussel (Dreissena
      polymorpha) are scarce. Moreover, this well-known invader is currently replaced
      by another, the quagga mussel (Dreissena rostriformis bugensis). To evaluate the
      differential tolerance between dreissenids, several populations of both species
      were exposed to a high concentration of nickel. A LT50 (time when 50% of
      individuals were dead) was established for each population. Biomarker responses
      and internal nickel concentration were also measured, to link tolerance with
      physiological status. Results evidenced that D. polymorpha populations are more
      heterogeneous and more tolerant than D. r. bugensis ones. For D. polymorpha
      populations only, LT50 values were positively correlated with the nickel
      contamination in situ, with higher anti-oxidative defences and a higher
      Integrated Biomarker Response value in the field. Such findings may be explained
      by local adaptation and invasion dynamic within each species. The significance of
      this differential tolerance when using biomarker responses for biomonitoring
      purposes is thus discussed.

PMID- 29335593
TI  - Bacterial iron reduction and biogenic mineral formation for the stabilisation of
      corroded iron objects.
AB  - Exploiting bacterial metabolism for the stabilisation of corroded iron artefacts
      is a promising alternative to conventional conservation-restoration methods.
      Bacterial iron reduction coupled to biogenic mineral formation has been shown to
      promote the conversion of reactive into stable corrosion products that are
      integrated into the natural corrosion layer of the object. However, in order to
      stabilise iron corrosion, the formation of specific biogenic minerals is
      essential. In this study, we used the facultative anaerobe Shewanella loihica for
      the production of stable biogenic iron minerals under controlled chemical
      conditions. The biogenic formation of crystalline iron phosphates was observed
      after iron reduction in a solution containing Fe(III) citrate. When the same
      biological treatment was applied on corroded iron plates, a layer composed of
      iron phosphates and iron carbonates was formed. Surface and cross-section
      analyses demonstrated that these two stable corrosion products replaced 81% of
      the reactive corrosion layer after two weeks of treatment. Such results
      demonstrate the potential of a biological treatment in the development of a
      stabilisation method to preserve corroded iron objects.

PMID- 29335594
TI  - Interfacial Coupling Effect on Electron Transport in MoS2/SrTiO3 Heterostructure:
      An Ab-initio Study.
AB  - A variety of theoretical and experimental works have reported several potential
      applications of MoS2 monolayer based heterostructures (HSs) such as light
      emitting diodes, photodetectors and field effect transistors etc. In the present
      work, we have theoretically performed as a model case study, MoS2 monolayer
      deposited over insulating SrTiO3 (001) to study the band alignment at TiO2
      termination. The interfacial characteristics are found to be highly dependent on
      the interface termination. With an insulating oxide material, a significant band
      gap (0.85eV) is found in MoS2/TiO2 interface heterostructure (HS). A unique
      electronic band profile with an indirect band gap (0.67eV) is observed in MoS2
      monolayer when confined in a cubic environment of SrTiO3 (STO). Adsorption
      analysis showed the chemisorption of MoS2 on the surface of STO substrate with
      TiO2 termination which is justified by the charge density calculations that shows
      the existence of covalent bonding at the interface. The fabrication of HS of such
      materials paves the path for developing the unprecedented 2D materials with
      exciting properties such as semiconducting devices, thermoelectric and
      optoelectronic applications.

PMID- 29335595
TI  - Mapping the epidemic changes and risks of hemorrhagic fever with renal syndrome
      in Shaanxi Province, China, 2005-2016.
AB  - Hemorrhagic fever with renal syndrome (HFRS) is a major rodent-borne zoonosis.
      Each year worldwide, 60,000-100,000 HFRS human cases are reported in more than
      seventy countries with almost 90% these cases occurring in China. Shaanxi
      Province in China has been among the most seriously affected areas since 1955.
      During 2009-2013, Shaanxi reported 11,400 human cases, the most of all provinces
      in China. Furthermore, the epidemiological features of HFRS have changed over
      time. Using long-term data of HFRS from 2005 to 2016, we carried out this
      retrospective epidemiological study combining ecological assessment models in
      Shaanxi. We found the majority of HFRS cases were male farmers who acquired
      infection in Guanzhong Plain, but the geographic extent of the epidemic has
      slowly spread northward. The highest age-specific attack rate since 2011 was
      among people aged 60-74 years, and the percentage of HFRS cases among the elderly
      increased from 12% in 2005 to 25% in 2016. We highly recommend expanding HFRS
      vaccination to people older than 60 years to better protect against the disease.
      Multivariate analysis revealed artificial area, cropland, pig and population
      density, GDP, and climate conditions (relative humidity, precipitation, and wind
      speed) as significant risk factors in the distribution of HFRS.

PMID- 29335596
TI  - Circulating microRNA signature for the diagnosis of childhood dilated
      cardiomyopathy.
AB  - Circulating miRNAs are proposed as a biomarker of heart disease. This study
      evaluated whether circulating miRNAs could be used as a biomarker for childhood
      dilated cardiomyopathy (CDCM). A total of 28 participants were enrolled in a
      discovery set, including patients with CDCM (n = 16) and healthy children (n =
      12). The cardiac function of patients with CDCM was characterized by
      echocardiography and serum miRNA profiles of all participants were assessed by
      miRNA sequencing. After miRNA profiling, we quantitatively confirmed 148
      regulated miRNAs in patients with CDCM compared with healthy subjects, and none
      were downregulated. Validation of candidate miRNAs was assessed by quantitative
      real-time polymerase chain reaction in other patients with CDCM (n = 30) and
      healthy controls (n = 16). A unique signature comprising mir-142-5p, mir-143-3p,
      mir-27b-3p, and mir-126-3p differentiated patients with CDCM from healthy
      subjects. Importantly, we observed an increase in mir-126-3p or let-7g in
      parallel with a robust decrease in the ejection fraction in patients with CDCM,
      which could differentiate heart failure patients from non-heart failure patients
      with CDCM. Moreover, mir-126-3p and let-7g were significantly negatively
      associated with the left ventricular ejection fraction. This study shows that a
      signature of four serum miRNAs may be a potential biomarker for diagnosing CDCM
      and assessing heart failure.

PMID- 29335597
TI  - Exercise Protects Against Olanzapine-Induced Hyperglycemia in Male C57BL/6J Mice.
AB  - Olanzapine is a widely prescribed antipsychotic drug. While effective in reducing
      psychoses, treatment with olanzapine causes rapid increases in blood glucose. We
      wanted to determine if a single bout of exercise, immediately prior to treatment,
      would attenuate the olanzapine-induced rise in blood glucose and if this occurred
      in an IL-6 dependent manner. We found that exhaustive, but not moderate exercise,
      immediately prior to treatment, prevented olanzapine-induced hyperglycemia and
      this occurred in parallel with increases in serum IL-6. To determine if IL-6 was
      involved in the mechanisms through which exhaustive exercise protected against
      olanzapine-induced hyperglycemia several additional experiments were completed.
      Treatment with IL-6 (3 ng/g bw, IP) alone did not protect against olanzapine
      induced increases in blood glucose. The protective effects of exhaustive exercise
      against olanzapine-induced increases in blood glucose were intact in whole body
      IL-6 knockout mice. Similarly, treating mice with an IL-6 neutralizing antibody
      prior to exhaustive exercise did not negate the protective effect of exercise
      against olanzapine-induced hyperglycemia. Our findings provide evidence that a
      single bout of exhaustive exercise protects against acute olanzapine-induced
      hyperglycemia and that IL-6 is neither sufficient, nor required for exercise to
      protect against increases in blood glucose with olanzapine treatment.

PMID- 29335598
TI  - Gene and MicroRNA Perturbations of Cellular Response to Pemetrexed Implicate
      Biological Networks and Enable Imputation of Response in Lung Adenocarcinoma.
AB  - Pemetrexed is indicated for non-small cell lung carcinoma and mesothelioma, but
      often has limited efficacy due to drug resistance. To probe the molecular
      mechanisms underlying chemotherapeutic response, we performed mRNA and microRNA
      (miRNA) expression profiling of pemetrexed treated and untreated lymphoblastoid
      cell lines (LCLs) and applied a hierarchical Bayesian method. We identified
      genetic variation associated with gene expression in human lung tissue for the
      most significant differentially expressed genes (Benjamini-Hochberg [BH] adjusted
      p < 0.05) using the Genotype-Tissue Expression data and found evidence for their
      clinical relevance using integrated molecular profiling and lung adenocarcinoma
      survival data from The Cancer Genome Atlas project. We identified 39 miRNAs with
      significant differential expression (BH adjusted p < 0.05) in LCLs. We developed
      a gene expression based imputation model of drug sensitivity, quantified its
      prediction performance, and found a significant correlation of the imputed
      phenotype generated from expression data with survival time in lung
      adenocarcinoma patients. Differentially expressed genes (MTHFD2 and SUFU) that
      are putative targets of differentially expressed miRNAs also showed differential
      perturbation in A549 fusion lung tumor cells with further replication in A549
      cells. Our study suggests pemetrexed may be used in combination with agents that
      target miRNAs to increase its cytotoxicity.

PMID- 29335599
TI  - Hindlimb Ischemia Impairs Endothelial Recovery and Increases Neointimal
      Proliferation in the Carotid Artery.
AB  - Peripheral ischemia is associated with higher degree of endothelial dysfunction
      and a worse prognosis after percutaneous coronary interventions (PCI). However,
      the role of peripheral ischemia on vascular remodeling in remote districts
      remains poorly understood. Here we show that the presence of hindlimb ischemia
      significantly enhances neointima formation and impairs endothelial recovery in
      balloon-injured carotid arteries. Endothelial-derived microRNAs are involved in
      the modulation of these processes. Indeed, endothelial miR-16 is remarkably
      upregulated after vascular injury in the presences of hindlimb ischemia and
      exerts a negative effect on endothelial repair through the inhibition of
      RhoGDIalpha and nitric oxide (NO) production. We showed that the repression of
      RhoGDIalpha by means of miR-16 induces RhoA, with consequent reduction of NO
      bioavailability. Thus, hindlimb ischemia affects negative carotid remodeling
      increasing neointima formation after injury, while systemic antagonizzation of
      miR-16 is able to prevent these negative effects.

PMID- 29335600
TI  - Alteration in Fluidity of Cell Plasma Membrane in Huntington Disease Revealed by
      Spectral Phasor Analysis.
AB  - Huntington disease (HD) is a late-onset genetic neurodegenerative disorder caused
      by expansion of cytosine-adenine-guanine (CAG) trinucleotide in the exon 1 of the
      gene encoding the polyglutamine (polyQ). It has been shown that protein
      degradation and lipid metabolism is altered in HD. In many neurodegenerative
      disorders, impaired lipid homeostasis is one of the early events in the disease
      onset. Yet, little is known about how mutant huntingtin may affect phospholipids
      membrane fluidity. Here, we investigated how membrane fluidity in the living
      cells (differentiated PC12 and HEK293 cell lines) are affected using a
      hyperspectral imaging of widely used probes, LAURDAN. Using phasor approach, we
      characterized the fluorescence of LAURDAN that is sensitive to the polarity of
      the immediate environment. LAURDAN is affected by the physical order of
      phospholipids (lipid order) and reports the membrane fluidity. We also validated
      our results using a different fluorescent membrane probe, Nile Red (NR). The
      plasma membrane in the cells expressing expanded polyQ shows a shift toward
      increased membrane fluidity revealed by both LAURDAN and NR spectral phasors.
      This finding brings a new perspective in the understanding of the early stages of
      HD that can be used as a target for drug screening.

PMID- 29335602
TI  - In situ single-shot diffractive fluence mapping for X-ray free-electron laser
      pulses.
AB  - Free-electron lasers (FELs) in the extreme ultraviolet (XUV) and X-ray regime
      opened up the possibility for experiments at high power densities, in particular
      allowing for fluence-dependent absorption and scattering experiments to reveal
      non-linear light-matter interactions at ever shorter wavelengths. Findings of
      such non-linear effects are met with tremendous interest, but prove difficult to
      understand and model due to the inherent shot-to-shot fluctuations in photon
      intensity and the often structured, non-Gaussian spatial intensity profile of a
      focused FEL beam. Presently, the focused beam is characterized and optimized
      separately from the actual experiment. Here, we present the simultaneous
      measurement of XUV diffraction signals from solid samples in tandem with the
      corresponding single-shot spatial fluence distribution on the actual sample. Our
      in situ characterization scheme enables direct monitoring of the sample
      illumination, providing a basis to optimize and quantitatively understand FEL
      experiments.

PMID- 29335601
TI  - Loss of CD14 leads to disturbed epithelial-B cell crosstalk and impairment of the
      intestinal barrier after E. coli Nissle monoassociation.
AB  - The TLR4 co-receptor CD14 was identified as an IBD candidate gene. Here, its
      influence on the intestinal barrier was addressed utilizing E. coli Nissle (EcN),
      which induces severe inflammation in germfree TLR4-/- mice. After
      monoassociation, EcN was detected in spleens and livers of TLR4-/- and CD14-/-
      but not wildtype mice. Barrier impairment was characterized by increased
      apoptosis and decreased epithelial junction (EJ) expression and was reversed by
      TLR2 stimulation in CD14-/- mice. Bone marrow (BM) transplantation revealed
      contribution of hematopoietic and non-hematopoietic cells towards intestinal
      homeostasis. EcN inoculated WT mice showed B cell activation, CD14-/- and TLR4-/-
      mice cytotoxic T cell and impaired B cell responses. The latter was characterized
      by absence of B cells in TLR4-/- mice, decreased levels of EcN induced
      immunoglobulins and downregulation of their transporter pIgR. EcN colonization of
      mice with genetically or antibody induced impaired B cell response resulted in
      dissemination of EcN and downregulation of EJ. BM chimeras indicated that CD14
      originating from radiation resistant cells is sufficient to restore EJ-function.
      Overall, CD14/TLR4 signalling seems to be critical for intestinal barrier
      function and for the crosstalk between B cells and the epithelium, underlining
      that CD14 serves as a protective modulator of intestinal homeostasis.

PMID- 29335603
TI  - In vivo simultaneous transcriptional activation of multiple genes in the brain
      using CRISPR-dCas9-activator transgenic mice.
AB  - Despite rapid progresses in the genome-editing field, in vivo simultaneous
      overexpression of multiple genes remains challenging. We generated a transgenic
      mouse using an improved dCas9 system that enables simultaneous and precise in
      vivo transcriptional activation of multiple genes and long noncoding RNAs in the
      nervous system. As proof of concept, we were able to use targeted activation of
      endogenous neurogenic genes in these transgenic mice to directly and efficiently
      convert astrocytes into functional neurons in vivo. This system provides a
      flexible and rapid screening platform for studying complex gene networks and gain
      of-function phenotypes in the mammalian brain.

PMID- 29335604
TI  - Dentate network activity is necessary for spatial working memory by supporting
      CA3 sharp-wave ripple generation and prospective firing of CA3 neurons.
AB  - Complex spatial working memory tasks have been shown to require both hippocampal
      sharp-wave ripple (SWR) activity and dentate gyrus (DG) neuronal activity. We
      therefore asked whether DG inputs to CA3 contribute to spatial working memory by
      promoting SWR generation. Recordings from DG and CA3 while rats performed a
      dentate-dependent working memory task on an eight-arm radial maze revealed that
      the activity of dentate neurons and the incidence rate of SWRs both increased
      during reward consumption. We then found reduced reward-related CA3 SWR
      generation without direct input from dentate granule neurons. Furthermore, CA3
      cells with place fields in not-yet-visited arms preferentially fired during SWRs
      at reward locations, and these prospective CA3 firing patterns were more
      pronounced for correct trials and were dentate-dependent. These results indicate
      that coordination of CA3 neuronal activity patterns by DG is necessary for the
      generation of neuronal firing patterns that support goal-directed behavior and
      memory.

PMID- 29335606
TI  - Conserved properties of dentate gyrus neurogenesis across postnatal development
      revealed by single-cell RNA sequencing.
AB  - The dentate gyrus of the hippocampus is a brain region in which neurogenesis
      persists into adulthood; however, the relationship between developmental and
      adult dentate gyrus neurogenesis has not been examined in detail. Here we used
      single-cell RNA sequencing to reveal the molecular dynamics and diversity of
      dentate gyrus cell types in perinatal, juvenile, and adult mice. We found
      distinct quiescent and proliferating progenitor cell types, linked by transient
      intermediate states to neuroblast stages and fully mature granule cells. We
      observed shifts in the molecular identity of quiescent and proliferating radial
      glia and granule cells during the postnatal period that were then maintained
      through adult stages. In contrast, intermediate progenitor cells, neuroblasts,
      and immature granule cells were nearly indistinguishable at all ages. These
      findings demonstrate the fundamental similarity of postnatal and adult
      neurogenesis in the hippocampus and pinpoint the early postnatal transformation
      of radial glia from embryonic progenitors to adult quiescent stem cells.

PMID- 29335605
TI  - Dietary salt promotes neurovascular and cognitive dysfunction through a gut
      initiated TH17 response.
AB  - A diet rich in salt is linked to an increased risk of cerebrovascular diseases
      and dementia, but it remains unclear how dietary salt harms the brain. We report
      that, in mice, excess dietary salt suppresses resting cerebral blood flow and
      endothelial function, leading to cognitive impairment. The effect depends on
      expansion of TH17 cells in the small intestine, resulting in a marked increase in
      plasma interleukin-17 (IL-17). Circulating IL-17, in turn, promotes endothelial
      dysfunction and cognitive impairment by the Rho kinase-dependent inhibitory
      phosphorylation of endothelial nitric oxide synthase and reduced nitric oxide
      production in cerebral endothelial cells. The findings reveal a new gut-brain
      axis linking dietary habits to cognitive impairment through a gut-initiated
      adaptive immune response compromising brain function via circulating IL-17. Thus,
      the TH17 cell-IL-17 pathway is a putative target to counter the deleterious brain
      effects induced by dietary salt and other diseases associated with TH17
      polarization.

PMID- 29335607
TI  - Grid scale drives the scale and long-term stability of place maps.
AB  - Medial entorhinal cortex (MEC) grid cells fire at regular spatial intervals and
      project to the hippocampus, where place cells are active in spatially restricted
      locations. One feature of the grid population is the increase in grid spatial
      scale along the dorsal-ventral MEC axis. However, the difficulty in perturbing
      grid scale without impacting the properties of other functionally defined MEC
      cell types has obscured how grid scale influences hippocampal coding and spatial
      memory. Here we use a targeted viral approach to knock out HCN1 channels
      selectively in MEC, causing the grid scale to expand while leaving other MEC
      spatial and velocity signals intact. Grid scale expansion resulted in place scale
      expansion in fields located far from environmental boundaries, reduced long-term
      place field stability and impaired spatial learning. These observations, combined
      with simulations of a grid-to-place cell model and position decoding of place
      cells, illuminate how grid scale impacts place coding and spatial memory.

PMID- 29335608
TI  - N6-methyladenosine RNA modification regulates embryonic neural stem cell self
      renewal through histone modifications.
AB  - Internal N6-methyladenosine (m6A) modification is widespread in messenger RNAs
      (mRNAs) and is catalyzed by heterodimers of methyltransferase-like protein 3
      (Mettl3) and Mettl14. To understand the role of m6A in development, we deleted
      Mettl14 in embryonic neural stem cells (NSCs) in a mouse model. Phenotypically,
      NSCs lacking Mettl14 displayed markedly decreased proliferation and premature
      differentiation, suggesting that m6A modification enhances NSC self-renewal.
      Decreases in the NSC pool led to a decreased number of late-born neurons during
      cortical neurogenesis. Mechanistically, we discovered a genome-wide increase in
      specific histone modifications in Mettl14 knockout versus control NSCs. These
      changes correlated with altered gene expression and observed cellular phenotypes,
      suggesting functional significance of altered histone modifications in knockout
      cells. Finally, we found that m6A regulates histone modification in part by
      destabilizing transcripts that encode histone-modifying enzymes. Our results
      suggest an essential role for m6A in development and reveal m6A-regulated histone
      modifications as a previously unknown mechanism of gene regulation in mammalian
      cells.

PMID- 29335610
TI  - Liquid-like thermal conduction in intercalated layered crystalline solids.
AB  - As a generic property, all substances transfer heat through microscopic
      collisions of constituent particles 1 . A solid conducts heat through both
      transverse and longitudinal acoustic phonons, but a liquid employs only
      longitudinal vibrations2,3. As a result, a solid is usually thermally more
      conductive than a liquid. In canonical viewpoints, such a difference also serves
      as the dynamic signature distinguishing a solid from a liquid. Here, we report
      liquid-like thermal conduction observed in the crystalline AgCrSe2. The
      transverse acoustic phonons are completely suppressed by the ultrafast dynamic
      disorder while the longitudinal acoustic phonons are strongly scattered but
      survive, and are thus responsible for the intrinsically ultralow thermal
      conductivity. This scenario is applicable to a wide variety of layered compounds
      with heavy intercalants in the van der Waals gaps, manifesting a broad
      implication on suppressing thermal conduction. These microscopic insights might
      reshape the fundamental understanding on thermal transport properties of matter
      and open up a general opportunity to optimize performances of thermoelectrics.

PMID- 29335611
TI  - Designing perturbative metamaterials from discrete models.
AB  - Identifying material geometries that lead to metamaterials with desired
      functionalities presents a challenge for the field. Discrete, or reduced-order,
      models provide a concise description of complex phenomena, such as negative
      refraction, or topological surface states; therefore, the combination of
      geometric building blocks to replicate discrete models presenting the desired
      features represents a promising approach. However, there is no reliable way to
      solve such an inverse problem. Here, we introduce 'perturbative metamaterials', a
      class of metamaterials consisting of weakly interacting unit cells. The weak
      interaction allows us to associate each element of the discrete model with
      individual geometric features of the metamaterial, thereby enabling a systematic
      design process. We demonstrate our approach by designing two-dimensional elastic
      metamaterials that realize Veselago lenses, zero-dispersion bands and topological
      surface phonons. While our selected examples are within the mechanical domain,
      the same design principle can be applied to acoustic, thermal and photonic
      metamaterials composed of weakly interacting unit cells.

PMID- 29335609
TI  - Prognostic significance of HALP (hemoglobin, albumin, lymphocyte and platelet) in
      patients with bladder cancer after radical cystectomy.
AB  - The outcome of bladder cancer after radical cystectomy is heterogeneous. We aim
      to evaluate the prognostic value of HALP (hemoglobin, albumin, lymphocyte and
      platelet) and explore novel prognostic indexes for patients with bladder cancer
      after radical cystectomy. In this retrospective study, 516 patients with bladder
      cancer after radical cystectomy were included. The median follow-up was 37 months
      (2 to 99 mo). Risk factors of decreased overall survival were older age, high TNM
      stage, high American Society of Anesthesiologists (ASA) grade and low HALP score.
      The predictive accuracy was better with HALP-based nomogram than TNM stage (C-
      index 0.76 +/- 0.039 vs. 0.708 +/- 0.041). By combining ASA grade and HALP, we
      created a novel index-HALPA score and found it an independent risk factor for
      decreased survival (HALPA score = 1, HR 1.624, 95% CI 1.139-2.314, P = 0.007;
      HALPA score = 2, HR 3.471, 95% CI: 1.861-6.472, P < 0.001).The present study
      identified the prognostic value of HALP and provided a novel index HALPA score
      for bladder cancer after radical cystectomy.

PMID- 29335612
TI  - Wrist circumference is associated with increased systolic blood pressure in
      children with overweight/obesity.
AB  - Wrist circumference is a clinical marker for insulin-resistance in
      overweight/obese children and adolescents. Insulin resistance is considered a
      major determinant of increased vascular resistance and hypertension. The aim of
      the study was to investigate the association between wrist circumference and
      systolic (S) and diastolic (D) blood pressure (BP) in a population of
      overweight/obese children and adolescents. A population of 1133 overweight/obese
      children and adolescents (n = 1133) were consecutively enrolled. Multivariate
      regression analyses were used to investigate the influence of independent
      variables on the variance of BP. The prevalence of hypertension was 21.74% in
      males and 28.95% in females (p = 0.048). The results showed that SBP was
      significantly associated with wrist circumference in both genders (p < 0.0001 for
      both comparisons). We found no association between DBP and wrist circumference in
      either gender. Wrist circumference accounted for 17% of the total variance of SBP
      in males and 14% in females. Wrist circumference, a marker of insulin resistance,
      is associated with increased SBP in overweight/obese children and adolescents,
      suggesting a role of insulin resistance in the pathogenesis and development of
      hypertension.

PMID- 29335613
TI  - Food items contributing to high dietary salt intake among Japanese adults in the
      2012 National Health and Nutrition Survey.

PMID- 29335614
TI  - Reliability of pulse waveform separation analysis responses to an orthostatic
      challenge.
AB  - Cardiovascular autonomic nervous system function can be assessed using an
      orthostatic challenge to induce arterial wave reflection. While arterial
      reflection is typically estimated using a central augmentation index, a superior
      estimation can be obtained using pulse wave separation analysis to estimate the
      aortic backward pressure wave (Pb). However, to be of value in a clinical or
      research setting, an assessment tool must be precise (reliable). Therefore, this
      study sought to determine the measurement precision of Pb responses to a modified
      tilt-table test. Twenty healthy adults (26.4 year (SD 5.2), 24.7 kg/m2 (SD 3.8),
      55% female) were tested in a fasted state on three different mornings separated
      by a maximum of seven days. Pressure waveforms were recorded on the left arm, and
      aortic waveforms were generated using a generalized transfer function.
      Subsequently, a physiologic flow waveform was assumed to separate the aortic
      pressure wave into its forward and timing-independent backward (Pb) components.
      The criterion intra-class correlation coefficient of >=0.75 was exceeded at
      baseline (0.79), following a 5-min tilt (0.75), and following a 5-min recovery
      from tilt (0.75). The standard error of measurement was 7%. These findings
      indicate that in a healthy cohort, the Pb response to an orthostatic challenge
      can be assessed with acceptable precision. The next step is to determine the
      sensitivity (validity) of this technique in identifying cardiovascular autonomic
      dysfunction in patient groups.

PMID- 29335615
TI  - Marinobufagenin is related to elevated central and 24-h systolic blood pressures
      in young black women: the African-PREDICT Study.
AB  - Marinobufagenin (MBG) is an endogenous steroidal alpha1-Na+K+-ATPase inhibitor.
      Because of its role in sodium handling, MBG has been associated with both
      antihypertensive and prohypertensive effects in normal physiology and pathology.
      MBG is positively associated with blood pressure in Dahl salt-sensitive rats
      exhibiting a similar hypertensive phenotype to black populations, characterized
      by impaired urinary Na+ excretion. However, clinical studies exploring blood
      pressure (BP)-related effects of MBG in black populations are scant. We
      determined whether the MBG/Na+ ratio (assessing the effectiveness of Na+
      excretion resistance to MBG) is related to systolic BP (SBP) in young black men
      and women, compared to whites. We included 331 apparently healthy participants
      (20-30 years) (42.9% black, 43.8% men) on a habitual diet. We obtained 24-h and
      central SBP, and 24-h urinary Na+ and MBG levels. We found no ethnic differences
      in MBG, Na+ or MBG/Na+. MBG excretion correlated positively with Na+ excretion in
      all groups and to SBP in white men and black women (p <= 0.011). In black women
      only SBP related positively to MBG/Na+ in single and multi-variable adjusted
      regression models: central SBP (R2 = 0.26; beta = 0.28; p = 0.039), 24-h SBP (R2
      = 0.46; beta = 0.30; p = 0.011), daytime (R2 = 0.38; beta = 0.28; p = 0.023) and
      nighttime SBP (R2 = 0.38; beta = 0.33; p = 0.009). In contrast, inverse
      associations of MBG/Na+ with nighttime SBP were evident in white women (r = 
      0.20; p = 0.038) but lost significance after multiple adjustments (R2 = 0.36;
      beta = -0.13; p = 0.12). We found independent positive associations of SBP with
      MBG/Na+ in black women. This data supports the concept that reduced MBG-mediated
      Na+ excretion can contribute to adverse hemodynamics.

PMID- 29335616
TI  - Roles of angiotensin II type 2 receptor in mice with fetal growth restriction.
AB  - Our previous report indicated that vascular injury enhances vascular remodeling
      in fetal growth restriction (FGR) mice. The angiotensin II type 2 receptor (AT2R)
      is relatively highly expressed in fetal mice. Therefore, we investigated the
      roles of AT2R in FGR-induced cardiovascular disease using AT2R knockout (AT2KO)
      mice. Dams (wild-type and AT2KO mice) were fed an isocaloric diet containing 20%
      protein (NP) or 8% protein (LP) until delivery. Arterial blood pressure, body
      weight, and histological changes in organs were investigated in offspring. The
      birth weight of offspring from dams fed an LP diet (LPO) was significantly lower
      than that of offspring from dams fed an NP diet. The heart/body and kidney/body
      weight ratios in AT2KO-LPO at 12 weeks of age were significantly higher than
      those in the other groups. Greater thickness of the left ventricular wall, larger
      cardiomyocyte size and enhancement of perivascular fibrosis were observed in
      AT2KO-LPO. Interestingly, mRNA expression of collagen I and inflammatory
      cytokines was markedly higher in the AT2KO-LPO heart at 6 weeks of age but not at
      12 weeks of age. AT2R signaling may be involved in cardiovascular disorders of
      adult offspring with FGR. Regulation of AT2R could contribute to preventing
      future cardiovascular disease in FGR offspring.

PMID- 29335617
TI  - Cardiovascular Function of Modern Pigs Does not Comply with Allometric Scaling
      Laws.
AB  - Growing concerns have been expressed regarding cardiovascular performance in
      modern farm pigs, which has been proposed as a critical factor contributing to
      the reduced adaptability of modern pigs to stress. Here we tested the hypothesis
      that cardiac dimensions and pump function in modern heavy farm pigs are
      disproportionally low for their body weight, and investigated potential
      underlying mechanisms. The results from the present study indeed demonstrate
      disproportionally low values for stroke volume and cardiac output in pigs with
      bodyweights over 150 kg. Importantly, these low values were not the result of
      impaired left ventricular (LV) systolic contractile function, but were due to a
      disproportionally small LV end-diastolic volume. The latter was associated with
      changes in determinants of LV passive stiffness, including (i) an increase in LV
      myocardial collagen, (ii) a shift from the compliant N2BA titin isoform towards
      the stiff N2B, and (iii) a marked elevation of aortic blood pressure. Taken
      together, these results demonstrate reduced pumping capacity of the hearts of
      heavy modern pigs, due to structural abnormalities in the LV myocardium.

PMID- 29335620
TI  - Maternal, dominance and additive genetic effects in Nile tilapia; influence on
      growth, fillet yield and body size traits.
AB  - There are only few studies of dominance effects in non-inbred aquaculture
      species, since commonly used mating designs often have low power to separate
      dominance, maternal and common environmental effects. Here, a factorial design
      with reciprocal cross, common rearing of eggs and subsequent lifecycle stages and
      pedigree assignment using DNA microsatellites was used to separate these effects
      and estimate dominance (d2) and maternal (m2) ratios in Nile tilapia for six
      commercial traits. The study included observations on 2524 offspring from 155
      full-sib families. Substantial contributions of dominance were observed (P <
      0.05) for body depth (BD) and body weight at harvest (BWH) with estimates of d2 =
      0.27 (s.e. 0.09) and 0.23 (s.e. 0.09), respectively in the current breeding
      population. In addition the study found maternal variance (P < 0.05) for BD, BWH,
      body thickness and fillet weight explaining ~10% of the observed phenotypic
      variance. For fillet yield (FY) and body length (BL), no evidence was found for
      either maternal or dominance variance. For traits exhibiting maternal variance,
      including this effect in evaluations caused substantial re-ranking of selection
      candidates, but the impact of including dominance effects was notably less.
      Breeding schemes may benefit from utilising maternal variance in increasing
      accuracy of evaluations, reducing bias, and developing new lines, but the
      utilisation of the dominance variance may require further refinement of parameter
      estimates.

PMID- 29335618
TI  - Long-Term Maintenance of Human Pluripotent Stem Cells on cRGDfK-Presenting
      Synthetic Surfaces.
AB  - Synthetic human pluripotent stem cell (hPSC) culture surfaces with defined
      physical and chemical properties will facilitate improved research and
      therapeutic applications of hPSCs. In this study, synthetic surfaces for hPSC
      culture in E8 medium were produced for screening by modifying two polymer brush
      coatings [poly(acrylamide-co-acrylic acid) (PAAA) and poly(acrylamide-co
      propargyl acrylamide) (PAPA)] to present single peptides. Adhesion of hPSC
      colonies was more consistently observed on surfaces modified with cRGDfK compared
      to surfaces modified with other peptide sequences tested. PAPA-coated polystyrene
      flasks with coupled cRGDfK (cRGDfK-PAPA) were then used for long-term studies of
      three hPSC lines (H9, hiPS-NHF1.3, Genea-02). Cell lines maintained for ten
      passages on cRGDfK-PAPA were assessed for colony morphology, proliferation rate,
      maintenance of OCT4 expression, cell viability at harvest, teratoma formation
      potential, and global gene expression as assessed by the PluriTestTM assay.
      cRGDfK-PAPA and control cultures maintained on GeltrexTM produced comparable
      results in most assays. No karyotypic abnormalities were detected in cultures
      maintained on cRGDfK-PAPA, while abnormalities were detected in cultures
      maintained on GeltrexTM, StemAdhereTM or SynthemaxTM. This is the first report of
      long term maintenance of hPSC cultures on the scalable, stable, and cost
      effective cRGDfK-PAPA coating.

PMID- 29335619
TI  - Cytokine MIF Enhances Blood-Brain Barrier Permeability: Impact for Therapy in
      Ischemic Stroke.
AB  - Ischemic stroke is a devastating disease with limited therapeutic options. It is
      very urgent to find a new target for drug development. Here we found that the
      blood level of MIF in ischemic stroke patients is upregulated. To figure out the
      pathological role of MIF in ischemic stroke, both in vitro and in vivo studies
      were conducted. For in vitro studies, primary cortical neuron cultures and adult
      rat brain endothelial cells (ARBECs) were subjected to oxygen-glucose deprivation
      (OGD)/reoxygenation. Middle cerebral artery occlusion (MCAo) rodent models were
      used for in vivo studies. The results show that MIF exerts no direct neuronal
      toxicity in primary culture but disrupts tight junction in ARBECs. Furthermore,
      administration of MIF following MCAo shows the deleterious influence on stroke
      induced injury by destroying the tight junction of blood-brain barrier and
      increasing the infarct size. In contrast, administration of MIF antagonist ISO-1
      has the profound neuroprotective effect. Our results demonstrate that MIF might
      be a good drug target for the therapy of stroke.

PMID- 29335621
TI  - Prognostic relevance of DNMT3A R882 mutations in AML patients undergoing non
      myeloablative conditioning hematopoietic stem cell transplantation.

PMID- 29335622
TI  - Topical vitamin D analog for chronic graft versus host disease of the skin.

PMID- 29335623
TI  - Sinusoidal obstruction syndrome/veno-occlusive disease after high-dose
      intravenous busulfan/melphalan conditioning therapy in high-risk Ewing Sarcoma.
AB  - This mono-institutional observational study was conducted to determine incidence,
      severity, risk factors, and outcome of sinusoidal obstruction syndrome/veno
      occlusive disease (SOS/VOD) in high-risk Ewing sarcoma (ES) patients treated with
      intravenous busulfan and melphalan (BU-MEL) followed by autologous stem cell
      transplantation (ASCT). During the past 10 years, 75 consecutive ES patients
      resulted evaluable for the analysis. After diagnosis of SOS/VOD, defibrotide
      therapy was started as soon as the medication was available. The variables
      analyzed as potential risk factors were: gender, patient's age at diagnosis,
      primary tumor site, disease stage, and prior radiation therapy (RT) given,
      focusing on RT liver exposure. The median age at diagnosis was 18.8 years. Five
      patients developed moderate to severe SOS/VOD (cumulative incidence, 6.67%). None
      of 32 pediatric patients (<=17 years) developed SOS/VOD (p = 0.0674). In
      univariate analysis, prior RT liver exposure resulted statistically significant
      (p = 0.0496). There was one death due to severe SOS/VOD. This study reports the
      largest series of high-risk ES patients treated with intravenous BU-MEL before
      ASCT. The incidence of SOS/VOD was lower when compared with other studies that
      used oral busulfan. Any prior RT liver exposure should be avoided. Earlier
      defibrotide treatment confirms to be effective.

PMID- 29335624
TI  - Beneficial impact of low-dose rabbit anti-thymocyte globulin in unrelated
      hematopoietic stem cell transplantation: focusing on difference between stem cell
      sources.

PMID- 29335626
TI  - Using liver elastography to diagnose sinusoidal obstruction syndrome in pediatric
      patients undergoing hematopoetic stem cell transplant.
AB  - Sinusoidal obstruction syndrome (SOS) is a potentially fatal complication of
      hematopoietic stem cell transplantation (HSCT). Traditional ultrasound (US) has
      poor sensitivity and specificity. US shear wave elastography (SWE) is a newer
      technology that measures liver stiffness. This is a single-institution,
      prospective cohort study evaluating SWE in patients younger than 21 years who
      received HSCT from December 2015 through June 2017. SOS was defined using the
      modified Seattle criteria. Subjects had US with SWE at three scheduled time
      points. t-tests were used to assess for difference between the groups and ROC
      curves were generated. Twenty-five patients were included. Five subjects
      developed SOS. At day +5 HSCT, SOS patients had SWE velocities that increased by
      0.25 +/- 0.21 m/s compared to 0.02 +/- 0.18 in patients without SOS (p = 0.020).
      At day +14, SOS patients had SWE velocities that significantly increased by 0.91
      m/s +/- 1.14 m/s compared to 0.03 m/s +/- 0.23 m/s in patients without SOS (p =
      0.010). SWE SOS diagnosis occurred on average 9 and 11 days before clinical and
      conventional US diagnosis, respectively. Patients who develop SOS have increased
      liver stiffness compared to patients who do not develop SOS. SWE changes occur
      before other imaging and clinical findings of SOS.

PMID- 29335625
TI  - The European Society for Blood and Marrow Transplantation (EBMT) Consensus
      Guidelines for the Detection and Treatment of Donor-specific Anti-HLA Antibodies
      (DSA) in Haploidentical Hematopoietic Cell Transplantation.
AB  - Haploidentical donors are now increasingly considered for transplantation in the
      absence of HLA-matched donors or when an urgent transplant is needed. Donor
      specific anti-HLA antibodies (DSA) have been recently recognized as an important
      barrier against successful engraftment of donor cells, which can affect
      transplant survival. DSA appear more prevalent in this type of transplant due to
      higher likelihood of alloimmunization of multiparous females against offspring's
      HLA antigens, and the degree of mismatch. Here we summarize the evidence for the
      role of DSA in the development of primary graft failure in haploidentical
      transplantation and provide consensus recommendations from the European Society
      for Blood and Marrow Transplant Group on testing, monitoring, and treatment of
      patients with DSA receiving haploidentical hematopoietic progenitor cell
      transplantation.

PMID- 29335627
TI  - A comparison of attitudes toward HSCT and survival estimations post HSCT across
      two pediatric Hematology-Oncology and Intensive Care departments in Canada.

PMID- 29335628
TI  - Endothelial cell damage in idiopathic pneumonia syndrome.

PMID- 29335629
TI  - A prospective, randomized evaluation of the feasibility of exergaming on patients
      undergoing hematopoietic stem cell transplantation.
AB  - The positive effects of physical and sports therapy for strain dependent physical
      practice and improved quality of life (QoL) are well known. Nevertheless, the
      available capacities and problem-oriented therapies in the setting of
      hematopoietic stem cell transplantation (HSCT) are limited. We conducted a
      prospective, randomized study among 42 HSCT recipients in order to investigate
      the influence of exergaming on Nintendo Wii(r) or classical physiotherapy (PT) on
      physical fitness and psychological well-being. The trial included evaluation of
      muscle strength, endurance, physical activity, distress, QoL, anxiety, and
      depression. Within the first 2 weeks after HSCT endurance, muscle strength and
      physical well-being decreased, while the value of distress increased
      significantly in both groups. However, exergaming on Nintendo Wii(r) resulted in
      a decrease of anxiety and depression and improved emotional well-being, while the
      PT group showed a contrariwise pattern of these features. Analysis of the FACT
      BMT revealed a decline of QoL domains 2 and 4 weeks after HSCT and an improvement
      afterwards. The decrease of functional status after HSCT was accompanied by a
      drop of QoL and an increase of distress in both groups. However, our prospective
      study demonstrates that exergaming using the Nintendo Wii(r) is feasible and well
      tolerated in HSCT recipients.

PMID- 29335630
TI  - Haploidentical stem cell transplantation cures autoimmune hepatitis and
      cerebrovascular disease in a patient with sickle cell disease.

PMID- 29335631
TI  - Impact of HLA allele mismatch at HLA-A, -B, -C, -DRB1, and -DQB1 on outcomes in
      haploidentical stem cell transplantation.
AB  - The impact of human leukocyte antigen (HLA) allele mismatch on transplant
      outcomes in haploidentical stem cell transplantation (haplo-SCT) has not been
      established. We retrospectively studied 595 patients with hematologic malignancy
      who received haplo-SCT. The impact of multiple HLA allele mismatches (HLA-A, -B, 
      C, -DRB1, and -DQB1) and each HLA allele mismatch on transplant outcomes was
      analyzed. Greater number of HLA allele disparity does not appear worsen outcome.
      As for each HLA locus, HLA-A mismatch correlated with decreased rate of platelet
      engraftment (HR 0.740, P = .003); HLA-B mismatch independently correlated with
      decreased relapse rate (HR 0.494, P = .032) and improved disease-free survival
      and overall survival (HR 0.514, P = .003; HR 0.494, P = .002, respectively); HLA
      C mismatch appeared to be protective for transplant-related mortality (TRM) (HR
      0.567, P = .039); HLA-DRB1 mismatch was associated with increased cumulative
      incidence of grade II-IV acute graft-vs.-host disease (GVHD) (HR 1.942, P =
      .002). No associations of any HLA mismatch with delayed neutrophil engraftment or
      increased cumulative incidence of chronic GVHD were observed. Our data indicated
      that high degree of HLA allele mismatches did not adversely affect transplant
      outcomes in haplo-SCT and each HLA allele mismatch had different effect.

PMID- 29335632
TI  - Long-term outcome analysis of reduced-intensity allogeneic stem cell
      transplantation in patients with mantle cell lymphoma: a retrospective study from
      the EBMT Lymphoma Working Party.
AB  - Reduced-intensity allogeneic stem cell transplantation (RIST) is usually reserved
      for patients with mantle cell lymphoma who relapse after an autoSCT. However, the
      long-term efficacy of RIST and its curative potential have not been clearly
      demonstrated. We studied the long-term outcome of patients receiving a RIST for
      MCL as reported to the EBMT. A total of 324 patients, median age 57 years (range
      31-70), underwent a RIST between 2000 and 2008; 43% of the patients had received
      >3 lines of prior therapy, including an autoSCT in 46%. Non-relapse mortality
      (NRM) was 10% at 100 days and 24% at 1 year and was lower for patients receiving
      anti-thymocyte globulin (ATG)/ALG (RR 0.59, p = 0.046). After a median follow-up
      of 72 months (range 3-159), 118 patients relapsed at a median of 8 months post
      RIST (range 1-117). The cumulative incidence of relapse was 25% and 40% at 1 and
      5 years, respectively, and was associated with chemorefractory disease (HR 0.49,
      p = 0.01) and the use of CAMPATH (HR 2.59, p = 0.0002). The 4-year progression
      free survival rate and overall survival rate was 31 and 40%, respectively. RIST
      results in long-term disease-free survival in about 30% of the patients,
      including those patients relapsing after a prior autoSCT.

PMID- 29335633
TI  - Long term survival among patients who are disease free at 1-year post allogeneic
      hematopoietic cell transplantation: a single center analysis of 389 consecutive
      patients.
AB  - Allogeneic hematopoietic cell transplantation (HCT) is associated with
      significant morbidity and mortality especially in the first year after HCT. In
      this study, we examine the long-term outcomes of patients who survived at least
      one year post HCT without evidence of relapse. We analyzed the records for 389
      consecutive patients receiving an allogeneic transplant from 2005 to 2016 from a
      MRD, MUD, or haploidentical donor, who were alive and disease free at one year
      post-transplant. Patient characteristics and outcome parameters were extracted
      from our institutional database where they had been prospectively entered. A
      total of 389 patients met the selection criteria with donor graft including MRD
      37%, MUD 39%, and Haploidenitcal relative 24%. The median follow-up of survivors
      from time of HCT was 48.2 months. The median overall survival and disease-free
      survival at 5 years after the first anniversary post HCT was 78 and 74%,
      respectively. The most common causes of late mortality were disease relapse,
      chronic GVHD and infections. The major risk factors for late mortality included
      chronic GVHD requiring immunosuppression, being transplanted between 2005 and
      2009 compared to later years and male sex. Patients with high risk disease risk
      index (DRI) had worse OS compared to low risk DRI. The risk factors for late
      relapse included male sex and high/very high disease risk index. The projected
      long-term survival of 1-year survivors following allogeneic HCT is excellent.
      However, some patients remain at high risk of late relapse and late mortality.
      Early referral to transplant, adopting post-transplant consolidation strategies
      for high risk patients, and implementing newer GVHD prevention methods are
      potential interventions to help minimize the risk of late relapse and death.

PMID- 29335634
TI  - The PII signaling protein from red algae represents an evolutionary link between
      cyanobacterial and Chloroplastida PII proteins.
AB  - PII superfamily consists of widespread signal transduction proteins found in all
      domains of life. Whereas they are well-studied in Archaea, Bacteria and
      Chloroplastida, no PII homolog has been analyzed in Rhodophyta (red algae), where
      PII is encoded by a chloroplast localized glnB gene. Here, we characterized
      relevant sensory properties of PII from the red alga Porphyra purpurea (PpPII) in
      comparison to PII proteins from different phyla of oxygenic phototrophs
      (cyanobacteria, Chlamydomonas and Physcomitrella) to assess evolutionary
      conservation versus adaptive properties. Like its cyanobacterial counterparts,
      PpPII binds ATP/ADP and 2-oxoglutarate in synergy with ATP. However, green algae
      and land plant PII proteins lost the ability to bind ADP. In contrast to PII
      proteins from green algae and land plants, PpPII enhances the activity of N
      acetyl-L-glutamate kinase (NAGK) and relieves it from feedback inhibition by
      arginine in a glutamine-independent manner. Like PII from Chloroplastida, PpPII
      is not able to interact with the cyanobacterial transcriptional co-activator
      PipX. These data emphasize the conserved role of NAGK as a major PII-interactor
      throughout the evolution of oxygenic phototrophs, and confirms the specific role
      of PipX for cyanobacteria. Our results highlight the PII signaling system in red
      algae as an evolutionary intermediate between Cyanobacteria and Chlorophyta.

PMID- 29335636
TI  - Saving seed microbiomes.
AB  - Plant seeds are home to diverse microbial communities whose composition is
      determined by plant genotype, environment, and management practices. Plant
      domestication is now recognized as an important driver of plant-associated
      microbial diversity. To what extent and how domestication affects seed
      microbiomes is less well studied. Here we propose a 'back-to-the-future' approach
      to harness seed microbiomes of wild relatives of crop cultivars to save and re
      instate missing beneficial seed microbes for improved plant tolerance to biotic
      and abiotic stress.

PMID- 29335635
TI  - The emergence of metabolic heterogeneity and diverse growth responses in isogenic
      bacterial cells.
AB  - Microorganisms adapt to frequent environmental changes through population
      diversification. Previous studies demonstrated phenotypic diversity in a clonal
      population and its important effects on microbial ecology. However, the dynamic
      changes of phenotypic composition have rarely been characterized. Also, cellular
      variations and environmental factors responsible for phenotypic diversity remain
      poorly understood. Here, we studied phenotypic diversity driven by metabolic
      heterogeneity. We characterized metabolic activities and growth kinetics of
      starved Escherichia coli cells subject to nutrient upshift at single-cell
      resolution. We observed three subpopulations with distinct metabolic activities
      and growth phenotypes. One subpopulation was metabolically active and immediately
      grew upon nutrient upshift. One subpopulation was metabolically inactive and non
      viable. The other subpopulation was metabolically partially active, and did not
      grow upon nutrient upshift. The ratio of these subpopulations changed dynamically
      during starvation. A long-term observation of cells with partial metabolic
      activities indicated that their metabolism was later spontaneously restored,
      leading to growth recovery. Further investigations showed that oxidative stress
      can induce the emergence of a subpopulation with partial metabolic activities.
      Our findings reveal the emergence of metabolic heterogeneity and associated
      dynamic changes in phenotypic composition. In addition, the results shed new
      light on microbial dormancy, which has important implications in microbial
      ecology and biomedicine.

PMID- 29335637
TI  - Expression profiling of host and virus during a coccolithophore bloom provides
      insights into the role of viral infection in promoting carbon export.
AB  - The cosmopolitan coccolithophore Emiliania huxleyi is a unicellular eukaryotic
      alga that forms vast blooms in the oceans impacting large biogeochemical cycles.
      These blooms are often terminated due to infection by the large dsDNA virus, E.
      huxleyi virus (EhV). It was recently established that EhV-induced modulation of
      E. huxleyi metabolism is a key factor for optimal viral infection cycle. Despite
      the huge ecological importance of this host-virus interaction, the ability to
      assess its spatial and temporal dynamics and its possible impact on nutrient
      fluxes is limited by current approaches that focus on quantification of viral
      abundance and biodiversity. Here, we applied a host and virus gene expression
      analysis as a sensitive tool to quantify the dynamics of this interaction during
      a natural E. huxleyi bloom in the North Atlantic. We used viral gene expression
      profiling as an index for the level of active infection and showed that the
      latter correlated with water column depth. Intriguingly, this suggests a possible
      sinking mechanism for removing infected cells as aggregates from the E. huxleyi
      population in the surface layer into deeper waters. Viral infection was also
      highly correlated with induction of host metabolic genes involved in host life
      cycle, sphingolipid, and antioxidant metabolism, providing evidence for
      modulation of host metabolism under natural conditions. The ability to track and
      quantify defined phases of infection by monitoring co-expression of viral and
      host genes, coupled with advance omics approaches, will enable a deeper
      understanding of the impact that viruses have on the environment.

PMID- 29335638
TI  - Clearcutting alters decomposition processes and initiates complex restructuring
      of fungal communities in soil and tree roots.
AB  - Forest management practices often severely affect forest ecosystem functioning.
      Tree removal by clearcutting is one such practice, producing severe impacts due
      to the total reduction of primary productivity. Here, we assessed changes to
      fungal community structure and decomposition activity in the soil, roots and
      rhizosphere of a Picea abies stand for a 2-year period following clearcutting
      compared to data from before tree harvest. We found that the termination of
      photosynthate flow through tree roots into soil is associated with profound
      changes in soil, both in decomposition processes and fungal community
      composition. The rhizosphere, representing an active compartment of high enzyme
      activity and high fungal biomass in the living stand, ceases to exist and starts
      to resemble bulk soil. Decomposing roots appear to separate from bulk soil and
      develop into hotspots of decomposition and important fungal biomass pools. We
      found no support for the involvement of ectomycorrhizal fungi in the
      decomposition of roots, but we found some evidence that root endophytic fungi may
      have an important role in the early stages of this process. In soil, activity of
      extracellular enzymes also decreased in the long term following the end of
      rhizodeposition by tree roots.

PMID- 29335639
TI  - Reply to the commentary "Uncultivated microbes-in need of their own
      nomenclature?"

PMID- 29335640
TI  - The stage of soil development modulates rhizosphere effect along a High Arctic
      desert chronosequence.
AB  - In mature soils, plant species and soil type determine the selection of root
      microbiota. Which of these two factors drives rhizosphere selection in barren
      substrates of developing desert soils has, however, not yet been established.
      Chronosequences of glacier forelands provide ideal natural environments to
      identify primary rhizosphere selection factors along the changing edaphic
      conditions of a developing soil. Here, we analyze changes in bacterial diversity
      in bulk soils and rhizospheres of a pioneer plant across a High Arctic glacier
      chronosequence. We show that the developmental stage of soil strongly modulates
      rhizosphere community assembly, even though plant-induced selection buffers the
      effect of changing edaphic factors. Bulk and rhizosphere soils host distinct
      bacterial communities that differentially vary along the chronosequence. Cation
      exchange capacity, exchangeable potassium, and metabolite concentration in the
      soil account for the rhizosphere bacterial diversity. Although the soil fraction
      (bulk soil and rhizosphere) explains up to 17.2% of the variation in bacterial
      microbiota, the soil developmental stage explains up to 47.7% of this variation.
      In addition, the operational taxonomic unit (OTU) co-occurrence network of the
      rhizosphere, whose complexity increases along the chronosequence, is loosely
      structured in barren compared with mature soils, corroborating our hypothesis
      that soil development tunes the rhizosphere effect.

PMID- 29335641
TI  - Benefit from decline: the primary transcriptome of Alteromonas macleodii str.
      Te101 during Trichodesmium demise.
AB  - Interactions between co-existing microorganisms deeply affect the physiology of
      the involved organisms and, ultimately, the function of the ecosystem as a whole.
      Copiotrophic Alteromonas are marine gammaproteobacteria that thrive during the
      late stages of phytoplankton blooms in the marine environment and in laboratory
      co-cultures with cyanobacteria such as Trichodesmium. The response of this
      heterotroph to the sometimes rapid and transient changes in nutrient supply when
      the phototroph crashes is not well understood. Here, we isolated and sequenced
      the strain Alteromonas macleodii str. Te101 from a laboratory culture of
      Trichodesmium erythraeum IMS101, yielding a chromosome of 4.63 Mb and a single
      plasmid of 237 kb. Increasing salinities to >=43 ppt inhibited the growth of
      Trichodesmium but stimulated growth of the associated Alteromonas. We
      characterized the transcriptomic responses of both microorganisms and identified
      the complement of active transcriptional start sites in Alteromonas at single
      nucleotide resolution. In replicate cultures, a similar set of genes became
      activated in Alteromonas when growth rates of Trichodesmium declined and
      mortality was high. The parallel activation of fliA, rpoS and of flagellar
      assembly and growth-related genes indicated that Alteromonas might have increased
      cell motility, growth, and multiple biosynthetic activities. Genes with the
      highest expression in the data set were three small RNAs (Aln1a-c) that were
      identified as analogs of the small RNAs CsrB-C in E. coli or RsmX-Z in pathogenic
      bacteria. Together with the carbon storage protein A (CsrA) homolog Te101_05290,
      these RNAs likely control the expression of numerous genes in responding to
      changes in the environment.

PMID- 29335642
TI  - Controlled dynamic screening of excitonic complexes in 2D semiconductors.
AB  - We report a combined theoretical/experimental study of dynamic screening of
      excitons in media with frequency-dependent dielectric functions. We develop an
      analytical model showing that interparticle interactions in an exciton are
      screened in the range of frequencies from zero to the characteristic binding
      energy depending on the symmetries and transition energies of that exciton. The
      problem of the dynamic screening is then reduced to simply solving the
      Schrodinger equation with an effectively frequency-independent potential.
      Quantitative predictions of the model are experimentally verified using a test
      system: neutral, charged and defect-bound excitons in two-dimensional monolayer
      WS2, screened by metallic, liquid, and semiconducting environments. The screening
      induced shifts of the excitonic peaks in photoluminescence spectra are in good
      agreement with our model.

PMID- 29335643
TI  - Decoding Musical Training from Dynamic Processing of Musical Features in the
      Brain.
AB  - Pattern recognition on neural activations from naturalistic music listening has
      been successful at predicting neural responses of listeners from musical
      features, and vice versa. Inter-subject differences in the decoding accuracies
      have arisen partly from musical training that has widely recognized structural
      and functional effects on the brain. We propose and evaluate a decoding approach
      aimed at predicting the musicianship class of an individual listener from dynamic
      neural processing of musical features. Whole brain functional magnetic resonance
      imaging (fMRI) data was acquired from musicians and nonmusicians during listening
      of three musical pieces from different genres. Six musical features, representing
      low-level (timbre) and high-level (rhythm and tonality) aspects of music
      perception, were computed from the acoustic signals, and classification into
      musicians and nonmusicians was performed on the musical feature and parcellated
      fMRI time series. Cross-validated classification accuracy reached 77% with nine
      regions, comprising frontal and temporal cortical regions, caudate nucleus, and
      cingulate gyrus. The processing of high-level musical features at right superior
      temporal gyrus was most influenced by listeners' musical training. The study
      demonstrates the feasibility to decode musicianship from how individual brains
      listen to music, attaining accuracy comparable to current results from automated
      clinical diagnosis of neurological and psychological disorders.

PMID- 29335645
TI  - The new genetics of intelligence.
AB  - Intelligence - the ability to learn, reason and solve problems - is at the
      forefront of behavioural genetic research. Intelligence is highly heritable and
      predicts important educational, occupational and health outcomes better than any
      other trait. Recent genome-wide association studies have successfully identified
      inherited genome sequence differences that account for 20% of the 50%
      heritability of intelligence. These findings open new avenues for research into
      the causes and consequences of intelligence using genome-wide polygenic scores
      that aggregate the effects of thousands of genetic variants.

PMID- 29335646
TI  - Dipeptidyl peptidase-4 inhibitors, pancreatic cancer and acute pancreatitis: A
      meta-analysis with trial sequential analysis.
AB  - The use of dipeptidyl peptidase-4 (DPP-4) inhibitors may be associated with
      pancreatic cancer and acute pancreatitis. Recent meta-analyses have reported
      conflicting findings. Therefore, we performed a meta-analysis to assess the risk
      of both pancreatic cancer and acute pancreatitis associated with the use of DPP-4
      inhibitors. We also used trial sequential analysis to evaluate whether the number
      of patients included was enough to reach conclusions. We included randomised
      controlled trials lasting 24 weeks or more that compared DPP-4 inhibitors with
      placebo or other antihyperglycaemic agents. A total of 59,404 patients were
      included. There was no relationship between the use of DPP-4 inhibitors and
      pancreatic cancer (Peto odds ratio 0.65; 95% CI 0.35-1.21), and the optimal
      sample size was reached to determine a number needed to harm (NNH) of 1000
      patients. DPP-4 inhibitors were associated with increased risk for acute
      pancreatitis (Peto odds ratio 1.72; 95% CI 1.18-2.53), with an NNH of 1066
      patients, but the optimal sample size for this outcome was not reached. In
      conclusion, there is no association between DPP-4 inhibitors and pancreatic
      cancer, and a small risk for acute pancreatitis was observed with DPP-4 inhibitor
      use, although the latter finding is not definitive.

PMID- 29335644
TI  - Runs of homozygosity: windows into population history and trait architecture.
AB  - Long runs of homozygosity (ROH) arise when identical haplotypes are inherited
      from each parent and thus a long tract of genotypes is homozygous. Cousin
      marriage or inbreeding gives rise to such autozygosity; however, genome-wide data
      reveal that ROH are universally common in human genomes even among outbred
      individuals. The number and length of ROH reflect individual demographic history,
      while the homozygosity burden can be used to investigate the genetic architecture
      of complex disease. We discuss how to identify ROH in genome-wide microarray and
      sequence data, their distribution in human populations and their application to
      the understanding of inbreeding depression and disease risk.

PMID- 29335647
TI  - Aged polymorphonuclear leukocytes cause fibrotic interstitial lung disease in the
      absence of regulation by B cells.
AB  - Pulmonary immunity requires tight regulation, as interstitial inflammation can
      compromise gas exchange and lead to respiratory failure. Here we found a greater
      number of aged CD11bhiL-selectinloCXCR4+ polymorphonuclear leukocytes (PMNs) in
      lung vasculature than in the peripheral circulation. Using pulmonary intravital
      microscopy, we observed lung PMNs physically interacting with B cells via beta2
      integrins; this initiated neutrophil apoptosis, which led to macrophage-mediated
      clearance. Genetic deletion of B cells led to the accumulation of aged PMNs in
      the lungs without systemic inflammation, which caused pathological fibrotic
      interstitial lung disease that was attenuated by the adoptive transfer of B cells
      or depletion of PMNs. Thus, the lungs are an intermediary niche in the PMN
      lifecycle wherein aged PMNs are regulated by B cells, which restrains their
      potential to cause pulmonary pathology.

PMID- 29335650
TI  - CNS cancer: TTFields improve survival.

PMID- 29335648
TI  - Rapid chromatin repression by Aire provides precise control of immune tolerance.
AB  - Aire mediates the expression of tissue-specific antigens in thymic epithelial
      cells to promote tolerance against self-reactive T lymphocytes. However, the
      mechanism that allows expression of tissue-specific genes at levels that prevent
      harm is unknown. Here we show that Brg1 generates accessibility at tissue
      specific loci to impose central tolerance. We found that Aire has an intrinsic
      repressive function that restricts chromatin accessibility and opposes Brg1
      across the genome. Aire exerted this repressive influence within minutes after
      recruitment to chromatin and restrained the amplitude of active transcription.
      Disease-causing mutations that impair Aire-induced activation also impair the
      protein's repressive function, which indicates dual roles for Aire. Together,
      Brg1 and Aire fine-tune the expression of tissue-specific genes at levels that
      prevent toxicity yet promote immune tolerance.

PMID- 29335649
TI  - Hyaluronic acid-based nano-sized drug carrier-containing Gellan gum microspheres
      as potential multifunctional embolic agent.
AB  - The purpose of this study was to develop a gellan gum-based multifunctional
      embolic agent. Calibrated spherical gellan gum and nanoparticle-containing gellan
      gum microspheres were prepared via water-in oil emulsification method. Self
      assembled nanoparticles composed of short-chain hyaluronic acid and
      polyethylenimine as the doxorubicin carrier were prepared. The short-chain
      hyaluronic acid/polyethylenimine/ doxorubicin (sHH/PH/Dox) with the mean size was
      140 +/- 8 nm. To examine sHH/PH/Dox nanoparticle uptake into cells, the results
      confirmed that sHH/PH nanoparticles as drug carrier can facilitate the transport
      of doxorubicin into HepG2 liver cancer cells. Subsequently, sHH/PH/Dox merged
      into the gellan gum (GG) microspheres forming GG/sHH/PH/Dox microsphere. After a
      drug release experiment lasting 45 days, the amount of released doxorubicin from
      285, 388, and 481 MUm GG/sHH/PH/Dox microspheres were approximately 4.8, 1.8 and
      1.1-fold above the IC50 value of the HepG2 cell. GG/sHH/PH/Dox microspheres were
      performed in rabbit ear embolization model and ischemic necrosis on ear was
      visible due to the vascular after 8 days. Regarding the application of this
      device in the future, we aim to provide better embolization agents for
      transcatheter arterial chemoembolization (TACE).

PMID- 29335651
TI  - Haematological cancer: Daratumumab proves effective in patients with newly
      diagnosed multiple myeloma.

PMID- 29335652
TI  - Kidney cancer: First-in-class HIF2alpha antagonist safe and effective.

PMID- 29335653
TI  - Will a global fund for cancer be the answer?

PMID- 29335654
TI  - Microwave SQUID Multiplexer Demonstration for Cosmic Microwave Background
      Imagers.
AB  - Key performance characteristics are demonstrated for the microwave SQUID
      multiplexer (umux) coupled to transition edge sensor (TES) bolometers that have
      been optimized for cosmic microwave background (CMB) observations. In a 64
      channel demonstration, we show that the umux produces a white, input referred
      current noise level of [Formula: see text] at -77 dB microwave probe tone power,
      which is well below expected fundamental detector and photon noise sources for a
      ground-based CMB-optimized bolometer. Operated with negligible photon loading, we
      measure [Formula: see text] in the TES-coupled channels biased at 65% of the
      sensor normal resistance. This noise level is consistent with that predicted from
      bolometer thermal fluctuation (i.e. phonon) noise. Furthermore, the power
      spectral density is white over a range of frequencies down to ~ 100 mHz, which
      enables CMB mapping on large angular scales that constrain the physics of
      inflation. Additionally, we report cross-talk measurements that indicate a level
      below 0.3%, which is less than the level of cross-talk from multiplexed readout
      systems in deployed CMB imagers. These measurements demonstrate the umux as a
      viable readout technique for future CMB imaging instruments.

PMID- 29335655
TI  - A Bifactor Approach to Model Multifaceted Constructs in Statistical Mediation
      Analysis.
AB  - Statistical mediation analysis allows researchers to identify the most important
      mediating constructs in the causal process studied. Identifying specific
      mediators is especially relevant when the hypothesized mediating construct
      consists of multiple related facets. The general definition of the construct and
      its facets might relate differently to an outcome. However, current methods do
      not allow researchers to study the relationships between general and specific
      aspects of a construct to an outcome simultaneously. This study proposes a
      bifactor measurement model for the mediating construct as a way to parse variance
      and represent the general aspect and specific facets of a construct
      simultaneously. Monte Carlo simulation results are presented to help determine
      the properties of mediated effect estimation when the mediator has a bifactor
      structure and a specific facet of a construct is the true mediator. This study
      also investigates the conditions when researchers can detect the mediated effect
      when the multidimensionality of the mediator is ignored and treated as
      unidimensional. Simulation results indicated that the mediation model with a
      bifactor mediator measurement model had unbiased and adequate power to detect the
      mediated effect with a sample size greater than 500 and medium a- and b-paths.
      Also, results indicate that parameter bias and detection of the mediated effect
      in both the data-generating model and the misspecified model varies as a function
      of the amount of facet variance represented in the mediation model. This study
      contributes to the largely unexplored area of measurement issues in statistical
      mediation analysis.

PMID- 29335657
TI  - Changing Gender Norms and Marriage Dynamics in the United States.
AB  - Using a regional measure of gender norms from the General Social Surveys together
      with marital histories from the Panel Study of Income Dynamics, this study
      explored how gender norms were associated with women's marriage dynamics between
      1968 and 2012. Results suggested that a higher prevalence of egalitarian gender
      norms predicted a decline in marriage formation. This decline was, however, only
      true for women without a college degree. For college-educated women, the
      association between gender norms and marriage formation became positive when
      gender egalitarianism prevailed. The findings also revealed an inverted U-shaped
      relationship between gender norms and divorce: an initial increase in divorce was
      observed when gender norms were predominantly traditional. The association,
      however, reversed as gender norms became egalitarian. No differences by education
      were found for divorce. The findings partially support the gender revolution
      framework but also highlight greater barriers to marriage for low-educated women
      as societies embrace gender equality.

PMID- 29335656
TI  - Hydrogen-Atom Transfer Oxidation with H2O2 Catalyzed by [FeII(1,2-bis(2,2'
      bipyridyl-6-yl)ethane(H2O)2]2+: Likely Involvement of a (MU-Hydroxo)(MU-1,2
      peroxo)diiron(III) Intermediate.
AB  - The iron(II) triflate complex (1) of 1,2-bis(2,2'-bipyridyl-6-yl)ethane, with two
      bipyridine moieties connected by an ethane bridge, was prepared. Addition of
      aqueous 30% H2O2 to an acetonitrile solution of 1 yielded 2, a green compound
      with lambdamax=710 nm. Moessbauer measurements on 2 showed a doublet with an
      isomer shift (delta) of 0.35 mm/s and a quadrupole splitting (DeltaEQ) of 0.86
      mm/s, indicative of an antiferromagnetically coupled diferric complex. Resonance
      Raman spectra showed peaks at 883, 556 and 451 cm-1 that downshifted to 832, 540
      and 441 cm-1 when 1 was treated with H218O2. All the spectroscopic data support
      the initial formation of a (MU-hydroxo)(MU-1,2-peroxo)diiron(III) complex that
      oxidizes carbon-hydrogen bonds. At 0 degrees C 2 reacted with cyclohexene to
      yield allylic oxidation products but not epoxide. Weak benzylic C-H bonds of
      alkylarenes were also oxidized. A plot of the logarithms of the second order rate
      constants versus the bond dissociation energies of the cleaved C-H bond showed an
      excellent linear correlation. Along with the observation that oxidation of the
      probe substrate 2,2-dimethyl-1-phenylpropan-1-ol yielded the corresponding ketone
      but no benzaldehyde, and the kinetic isotope effect, kH/kD , of 2.8 found for the
      oxidation of xanthene, the results support the hypothesis for a metal-based H
      atom abstraction mechanism. Complex 2 is a rare example of a (MU-hydroxo)(MU-1,2
      peroxo)diiron(III) complex that can elicit the oxidation of carbon-hydrogen
      bonds.

PMID- 29335659
TI  - Recommendation System for Adaptive Learning.
AB  - An adaptive learning system aims at providing instruction tailored to the current
      status of a learner, differing from the traditional classroom experience. The
      latest advances in technology make adaptive learning possible, which has the
      potential to provide students with high-quality learning benefit at a low cost. A
      key component of an adaptive learning system is a recommendation system, which
      recommends the next material (video lectures, practices, and so on, on different
      skills) to the learner, based on the psychometric assessment results and possibly
      other individual characteristics. An important question then follows: How should
      recommendations be made? To answer this question, a mathematical framework is
      proposed that characterizes the recommendation process as a Markov decision
      problem, for which decisions are made based on the current knowledge of the
      learner and that of the learning materials. In particular, two plain vanilla
      systems are introduced, for which the optimal recommendation at each stage can be
      obtained analytically.

PMID- 29335658
TI  - Highly Stereoselective Asymmetric Aldol Routes to tert-Butyl-2-(3,5
      difluorophenyl)-1-oxiran-2-yl)ethyl)carbamates: Building Blocks for Novel
      Protease Inhibitors.
AB  - Enantioselective syntheses of tert-butyl ((S)-2-(3,5-difluorophenyl)-1-((S)
      oxiran-2-yl)ethyl)carbamate and ((S)-2-(3,5-difluorophenyl)-1-((R)-oxiran-2
      yl)ethyl)carbamate are described. We utilized asymmetric syn- and anti-aldol
      reactions to set both stereogenic centers. We investigated ester-derived Ti
      enolate aldol reactions as well as Evans' diastereoselective syn-aldol reaction
      for these syntheses. We have converted optically active ((S)-2-(3,5
      difluorophenyl)-1-((S)-oxiran-2-yl)ethyl)carbamate to a potent beta-secretase
      inhibitor.

PMID- 29335660
TI  - Can Linear Superiorization Be Useful for Linear Optimization Problems?
AB  - Linear superiorization considers linear programming problems but instead of
      attempting to solve them with linear optimization methods it employs perturbation
      resilient feasibility-seeking algorithms and steers them toward reduced (not
      necessarily minimal) target function values. The two questions that we set out to
      explore experimentally are (i) Does linear superiorization provide a feasible
      point whose linear target function value is lower than that obtained by running
      the same feasibility-seeking algorithm without superiorization under identical
      conditions? and (ii) How does linear superiorization fare in comparison with the
      Simplex method for solving linear programming problems? Based on our
      computational experiments presented here, the answers to these two questions are:
      "yes" and "very well", respectively.

PMID- 29335661
TI  - Weather Correlations to Calculate Infiltration Rates for U. S. Commercial
      Building Energy Models.
AB  - As building envelope performance improves, a greater percentage of building
      energy loss will occur through envelope leakage. Although the energy impacts of
      infiltration on building energy use can be significant, current energy simulation
      software have limited ability to accurately account for envelope infiltration and
      the impacts of improved airtightness. This paper extends previous work by the
      National Institute of Standards and Technology that developed a set of EnergyPlus
      inputs for modeling infiltration in several commercial reference buildings using
      Chicago weather. The current work includes cities in seven additional climate
      zones and uses the updated versions of the prototype commercial building types
      developed by the Pacific Northwest National Laboratory for the U. S. Department
      of Energy. Comparisons were made between the predicted infiltration rates using
      three representations of the commercial building types: PNNL EnergyPlus models,
      CONTAM models, and EnergyPlus models using the infiltration inputs developed in
      this paper. The newly developed infiltration inputs in EnergyPlus yielded average
      annual increases of 3 % and 8 % in the HVAC electrical and gas use, respectively,
      over the original infiltration inputs in the PNNL EnergyPlus models. When
      analyzing the benefits of building envelope airtightening, greater HVAC energy
      savings were predicted using the newly developed infiltration inputs in
      EnergyPlus compared with using the original infiltration inputs. These results
      indicate that the effects of infiltration on HVAC energy use can be significant
      and that infiltration can and should be better accounted for in whole-building
      energy models.

PMID- 29335662
TI  - Is Nebulin the Product of Duchenne Muscular Dystrophy Gene?

PMID- 29335663
TI  - Improving Mental Health Treatment Utilization in Military Veterans: Examining the
      Effects of Perceived Need for Care and Social Support.
AB  - Objective: Many veterans with mental health problems do not adequately utilize
      needed care. Research has focused on identifying barriers to mental health care
      in veterans. Method: The current study adds to existing literature by examining
      whether perceived need for treatment and social support affect treatment
      utilization in a national longitudinal survey of Iraq and Afghanistan veterans (n
      = 1090). Results: The Health Beliefs Model (HBM) postulates that a key reason why
      patients fail to obtain needed care is their belief "it's up to me to handle my
      own problems." This view was endorsed by 42% in the current national sample of
      veterans and was found in multivariate analysis to predict less treatment seeking
      in the next year. Mediation analysis revealed that veterans with higher ratings
      of social support were less likely to believe they needed to solve mental health
      problems on their own, indirectly equating to higher odds of treatment use.
      Simultaneously, findings indicated that posttraumatic stress disorder (PTSD) had
      a direct effect on more mental health visits but was also associated with higher
      endorsement that one needed to handle one's own problems and thus had an indirect
      effect of reducing mental health visits. Conclusion: Both social support and PTSD
      affected veterans' perceptions of needing to solve one's own problems,
      significantly predicted follow-up with mental health care. As a result, the
      findings indicate that clinicians' should explore veterans' belief systems about
      perceived treatment need as well as investigate the role of social support to
      improve mental health treatment utilization.

PMID- 29335664
TI  - Applying a biodeposition layer to increase the bond of a repair mortar on a
      mortar substrate.
AB  - One of the major concerns in infrastructure repair is a sufficient bond between
      the substrate and the repair material, especially for the long-term performance
      and durability of the repaired structure. In this study, the bond of the repair
      material on the mortar substrate is promoted via the biodeposition of a calcium
      carbonate layer by a ureolytic bacterium. X-ray diffraction and scanning electron
      microscopy were used to examine the interfaces between the repair material and
      the substrate, as well as the polymorph of the deposited calcium carbonate. The
      approximately 50 MUm thick biodeposition film on the mortar surface mostly
      consisted of calcite and vaterite. Both the repair material and the substrate
      tended to show a good adherence to that layer. The bond, as assessed by slant
      shear specimen testing, was improved by the presence of the biodeposition layer.
      A further increase was found when engineering the substrate surface using a
      structured pattern layer of biodeposition.

PMID- 29335665
TI  - Self-Control as Value-Based Choice.
AB  - Self-control is often conceived as a battle between "hot" impulsive processes and
      "cold" deliberative ones. Heeding the angel on one shoulder leads to success;
      following the demon on the other leads to failure. Self-control feels like a
      duality. What if that sensation is misleading, and, despite how they feel, self
      control decisions are just like any other choice? We argue that self-control is a
      form of value-based choice wherein options are assigned a subjective value and a
      decision is made through a dynamic integration process. We articulate how a value
      based choice model of self-control can capture its phenomenology and account for
      relevant behavioral and neuroscientific data. This conceptualization of self
      control links divergent scientific approaches, allows for more robust and precise
      hypothesis testing, and suggests novel pathways to improve self-control.

PMID- 29335666
TI  - A Modified Dynamic Surface Controller for Delayed Neuromuscular Electrical
      Stimulation.
AB  - A widely accepted model of muscle force generation during neuromuscular
      electrical stimulation (NMES) is a second-order nonlinear musculoskeletal
      dynamics cascaded to a delayed first-order muscle activation dynamics. However,
      most nonlinear NMES control methods have either neglected the muscle activation
      dynamics or used an ad hoc strategies to tackle the muscle activation dynamics,
      which may not guarantee control stability. We hypothesized that a nonlinear
      control design that includes muscle activation dynamics can improve the control
      performance. In this paper, a dynamic surface control (DSC) approach was used to
      design a PID-based NMES controller that compensates for EMD in the activation
      dynamics. Because the muscle activation is unmeasurable, a model based estimator
      was used to estimate the muscle activation in realtime. The Lyapunov stability
      analysis confirmed that the newly developed controller achieves semi-global
      uniformly ultimately bounded (SGUUB) tracking for the musculoskeletal system.
      Experiments were performed on two able-bodied subjects and one spinal cord injury
      subject using a modified leg extension machine. These experiments illustrate the
      performance of the new controller and compare it to a previous PID-DC controller
      that did not consider muscle activation dynamics in the control design. These
      experiments support our hypothesis that a control design that includes muscle
      activation improves the NMES control performance.

PMID- 29335667
TI  - Zero-inflated multiscale models for aggregated small area health data.
AB  - It is our primary focus to study the spatial distribution of disease incidence at
      different geographical levels. Often, spatial data are available in the form of
      aggregation at multiple scale levels such as census tract, county, state, and so
      on. When data are aggregated from a fine (e.g. county) to a coarse (e.g. state)
      geographical level, there will be loss of information. The problem is more
      challenging when excessive zeros are available at the fine level. After data
      aggregation, the excessive zeros at the fine level will be reduced at the coarse
      level. If we ignore the zero inflation and the aggregation effect, we could get
      inconsistent risk estimates at the fine and coarse levels. Hence, in this paper,
      we address those problems using zero inflated multiscale models that jointly
      describe the risk variations at different geographical levels. For the excessive
      zeros at the fine level, we use a zero inflated convolution model, whereas we
      consider a regular convolution model for the smoothed data at the coarse level.
      These methods provide a consistent risk estimate at the fine and coarse levels
      when high percentages of structural zeros are present in the data.

PMID- 29335668
TI  - Bayesian Empirical Likelihood Methods for Quantile Comparisons.
AB  - Bayes factors, practical tools of applied statistics, have been dealt with
      extensively in the literature in the context of hypothesis testing. The Bayes
      factor based on parametric likelihoods can be considered both as a pure Bayesian
      approach as well as a standard technique to compute p-values for hypothesis
      testing. We employ empirical likelihood methodology to modify Bayes factor type
      procedures for the nonparametric setting. The paper establishes asymptotic
      approximations to the proposed procedures. These approximations are shown to be
      similar to those of the classical parametric Bayes factor approach. The proposed
      approach is applied towards developing testing methods involving quantiles, which
      are commonly used to characterize distributions. We present and evaluate one and
      two sample distribution free Bayes factor type methods for testing quantiles
      based on indicators and smooth kernel functions. An extensive Monte Carlo study
      and real data examples show that the developed procedures have excellent
      operating characteristics for one-sample and two-sample data analysis.

PMID- 29335669
TI  - Portable FAIMS: Applications and Future Perspectives.
AB  - Miniaturized mass spectrometry (MMS) is optimal for a wide variety of
      applications that benefit from field-portable instrumentation. Like MMS, field
      asymmetric ion mobility spectrometry (FAIMS) has proven capable of providing in
      situ analysis, allowing researchers to bring the lab to the sample. FAIMS
      compliments MMS very well, but has the added benefit of operating at atmospheric
      pressure, unlike MS. This distinct advantage makes FAIMS uniquely suited for
      portability. Since its inception, FAIMS has been envisioned as a field-portable
      device, as it affords less expense and greater simplicity than many similar
      methods. Ideally, these are simple, robust devices that may be operated by non
      professional personnel, yet still provide adequate data when in the field. While
      reducing the size and complexity tends to bring with it a loss of performance and
      accuracy, this is made up for by the incredibly high throughput and overall
      convenience of the instrument. Moreover, the FAIMS device used in the field can
      be brought back to the lab, and coupled to a conventional mass spectrometer to
      provide any necessary method development and compound validation. This work
      discusses the various considerations, uses, and applications for portable FAIMS
      instrumentation, and how the future of each applicable field may benefit from the
      development and acceptance of such a device.

PMID- 29335670
TI  - Big Data and Neuroimaging.
AB  - Big Data are of increasing importance in a variety of areas, especially in the
      biosciences. There is an emerging critical need for Big Data tools and methods,
      because of the potential impact of advancements in these areas. Importantly,
      statisticians and statistical thinking have a major role to play in creating
      meaningful progress in this arena. We would like to emphasize this point in this
      special issue, as it highlights both the dramatic need for statistical input for
      Big Data analysis and for a greater number of statisticians working on Big Data
      problems. We use the field of statistical neuroimaging to demonstrate these
      points. As such, this paper covers several applications and novel methodological
      developments of Big Data tools applied to neuroimaging data.

PMID- 29335671
TI  - Feasibility, Acceptability, and Preliminary Effectiveness of a 4-week Mindfulness
      Based Cognitive Therapy Protocol for Hospital Employees.
AB  - Hospital employees may experience occupational stress and burnout, which
      negatively impact quality of life and job performance. Evidence-based
      interventions implemented within the hospital setting are needed to promote
      employees' well-being. We offered a 4-week Mindfulness-Based Cognitive Therapy
      group program for hospital employees, and used a mixed-methods practice-based
      research approach to explore feasibility, acceptability, and effects on stress
      and burnout. Participants were 65 hospital employees (Mage = 44.06; 85% white)
      who participated between September 2015 and January 2016. Participants completed
      validated measures of stress and burnout before and after the program, and
      answered open-ended satisfaction questions after the program. Groups consistently
      enrolled at least 10 participants, but attendance rates declined across sessions
      (76% at session 2 vs. 54% at session 4) due primarily to work-related scheduling
      conflicts. The program content was acceptable as evidenced by high perceived
      value (M = 9.18 out of 10), homework compliance (51% practicing at least 3
      times/week), and qualitative requests for program expansion. There were large,
      statistically significant decreases in stress (DeltaM = 2.1, p < .001, d = .85)
      and medium decreases in burnout (DeltaM = .46, p = .01, d = .57), which were
      supported by qualitative themes of improved self-regulation and mindfulness
      skills, stress reduction, emotional well-being, and improved work productivity
      and patient care skills. Findings suggest that 4-week MBCT is acceptable and
      useful for hospital employees, though research is needed to identify alternate
      delivery methods or strategies to enhance session attendance.

PMID- 29335672
TI  - Seeing Roses in the Thorn Bush: Sexual Assault Survivors' Perceptions of Social
      Reactions.
AB  - Objective: After sexual assault, survivors often reach to others for support and
      receive a range of reactions. Although these reactions have been characterized by
      researchers as positive (e.g., emotional support) or negative (e.g., victim
      blaming), survivors vary in their perceptions in ways that do not always match
      this framework. The goal of this research was to examine the degree to which
      designations of reactions as "positive" or "negative" fits across types of
      reactions and explain instances of mismatch between these designations and
      survivors' perceptions. Method: We conducted a qualitative analysis of interviews
      with 26 survivors of sexual assault to identify themes in their perceptions of
      social reactions. Results: Although social reactions were generally perceived in
      a manner that matched researcher categorizations, there was significant
      variation. Perceptions could be characterized in terms of whether the reaction
      felt comfortable/soothing, consistent with survivors' needs/hopes/expectations,
      and helpful in the long term. The closeness of survivors' relationships with
      responders, the degree to which they were impacted by the assault, and the
      presence of other social reactions explained variation from researcher
      designations of reaction types. Conclusion: This study clarifies the
      considerations that survivors make when evaluating social reactions and what
      accounts for discrepant perceptions of these reactions; in particular, they
      highlight that there is no "one size fits all" reaction to survivors of sexual
      assault and the context in which reactions occur may affect how they are seen.

PMID- 29335673
TI  - Desistance and Severity of Alcohol Use Disorder: A Lifespan-Developmental
      Investigation.
AB  - Key to an understanding of alcohol use disorder (AUD) are the drinking-related
      reductions that begin in young adulthood and continue throughout the adult
      lifespan. Research is needed to precisely characterize the form of these
      reductions, including possible developmental differences across the lifespan.
      Using U.S.-representative data, we estimated multiple-group Markov models
      characterizing longitudinal transitions among five drinking statuses and
      differences in transition patterns across six adult age periods. While past
      research indicates relative developmental stability in overall AUD-desistance
      rates, we found far higher rates of Severe-AUD desistance in young adulthood
      relative to later ages. Especially considering the dramatic change reflected by
      Severe-AUD desistance (from 6+ symptoms to 0-1 symptoms), this result indicates a
      substantial developmental shift, with Severe-AUD-desistance rates peaking at 43
      50% across ages 25-34 and then dropping to 22-24% across ages 35-55. We discuss
      implications regarding practical significance of young-adult "maturing out" and
      predictions regarding lifespan variability in desistance mechanisms.

PMID- 29335675
TI  - Exit, cohesion, and consensus: social psychological moderators of consensus among
      adolescent peer groups.
AB  - Virtually all social diffusion work relies on a common formal basis, which
      predicts that consensus will develop among a connected population as the result
      of diffusion. In spite of the popularity of social diffusion models that predict
      consensus, few empirical studies examine consensus, or a clustering of attitudes,
      directly. Those that do either focus on the coordinating role of strict
      hierarchies, or on the results of online experiments, and do not consider how
      consensus occurs among groups in situ. This study uses longitudinal data on
      adolescent social networks to show how meso-level social structures, such as
      informal peer groups, moderate the process of consensus formation. Using a novel
      method for controlling for selection into a group, I find that centralized peer
      groups, meaning groups with clear leaders, have very low levels of consensus,
      while cohesive peer groups, meaning groups where more ties hold the members of
      the group together, have very high levels of consensus. This finding is robust to
      two different measures of cohesion and consensus. This suggests that consensus
      occurs either through central leaders' enforcement or through diffusion of
      attitudes, but that central leaders have limited ability to enforce when people
      can leave the group easily.

PMID- 29335676
TI  - Behavioral Assays to Study Oxygen and Carbon Dioxide Sensing in Caenorhabditis
      elegans.
AB  - Animals use behavioral strategies to seek optimal environments. Population
      behavioral assays provide a robust means to determine the effect of genetic
      perturbations on the ability of animals to sense and respond to changes in the
      environment. Here, we describe a C. elegans population behavioral assay used to
      measure locomotory responses to changes in environmental oxygen (O2) and carbon
      dioxide (CO2) concentrations. These behavioral assays are high-throughput and
      enable examination of genetic, neuronal and circuit function.

PMID- 29335677
TI  - Two-dimensional imaging and modification of nanophotonic resonator modes using a
      focused ion beam.
AB  - High-resolution imaging of optical resonator modes is a key step in the
      development and characterization of nanophotonic devices. Many sub-wavelength
      mode-imaging techniques have been developed using optical and electron beam
      excitation-each with its own limitations in spectral and spatial resolution.
      Here, we report a 2D imaging technique using a pulsed, low-energy focused ion
      beam of Li+ to probe the near-surface fields inside photonic resonators. The ion
      beam locally modifies the resonator structure, causing temporally varying
      spectroscopic shifts of the resonator. We demonstrate this imaging technique on
      several optical modes of silicon microdisk resonators by rastering the ion beam
      across the disk surface and extracting the maximum mode shift at the location of
      each ion pulse. A small shift caused by ion beam heating is also observed and is
      independently extracted to directly measure the thermal response of the device.
      This technique enables visualization of the splitting of degenerate modes into
      spatially-resolved standing waves and permits persistent optical mode editing.
      Ion beam probing enables minimally perturbative, in operando imaging of
      nanophotonic devices with high resolution and speed.

PMID- 29335674
TI  - Noble metal nanoparticles in biosensors: recent studies and applications.
AB  - The aim of this review is to cover advances in noble metal nanoparticle (MNP)
      based biosensors and to outline the principles and main functions of MNPs in
      different classes of biosensors according to the transduction methods employed.
      The important biorecognition elements are enzymes, antibodies, aptamers, DNA
      sequences, and whole cells. The main readouts are electrochemical (amperometric
      and voltametric), optical (surface plasmon resonance, colorimetric,
      chemiluminescence, photoelectrochemical, etc.) and piezoelectric. MNPs have
      received attention for applications in biosensing due to their fascinating
      properties. These properties include a large surface area that enhances
      biorecognizers and receptor immobilization, good ability for reaction catalysis
      and electron transfer, and good biocompatibility. MNPs can be used alone and in
      combination with other classes of nanostructures. MNP-based sensors can lead to
      significant signal amplification, higher sensitivity, and great improvements in
      the detection and quantification of biomolecules and different ions. Some recent
      examples of biomolecular sensors using MNPs are given, and the effects of
      structure, shape, and other physical properties of noble MNPs and nanohybrids in
      biosensor performance are discussed.

PMID- 29335678
TI  - Does mental context drift or shift?
AB  - Theories of episodic memory have generally proposed that individual memory traces
      are linked together by a representation of context that drifts slowly over time.
      Recent data challenge the notion that contextual drift is always slow and
      passive. In particular, changes in one's external environment or internal model
      induce discontinuities in memory that are reflected in sudden changes in neural
      activity, suggesting that context can shift abruptly. Furthermore, context change
      effects are sensitive to top-down goals, suggesting that contextual drift may be
      an active process. These findings call for revising models of the role of context
      in memory, in order to account for abrupt contextual shifts and the controllable
      nature of context change.

PMID- 29335679
TI  - Deep Tissue Imaging with Multiphoton Fluorescence Microscopy.
AB  - We present a review of imaging deep-tissue structures with multiphoton
      microscopy. We examine the effects of light scattering and absorption due to the
      optical properties of biological sample and identify 1,300 nm and 1,700 nm as
      ideal excitation wavelengths. We summarize the availability of fluorophores for
      multiphoton microscopy as well as ultrafast laser sources to excite available
      fluorophores. Lastly, we discuss the applications of multiphoton microscopy for
      neuroscience.

PMID- 29335680
TI  - Flows, scaling, and the control of moment hierarchies for stochastic chemical
      reaction networks.
AB  - Stochastic chemical reaction networks (CRNs) are complex systems that combine the
      features of concurrent transformation of multiple variables in each elementary
      reaction event and nonlinear relations between states and their rates of change.
      Most general results concerning CRNs are limited to restricted cases where a
      topological characteristic known as deficiency takes a value 0 or 1, implying
      uniqueness and positivity of steady states and surprising, low-information forms
      for their associated probability distributions. Here we derive equations of
      motion for fluctuation moments at all orders for stochastic CRNs at general
      deficiency. We show, for the standard base case of proportional sampling without
      replacement (which underlies the mass-action rate law), that the generator of the
      stochastic process acts on the hierarchy of factorial moments with a finite
      representation. Whereas simulation of high-order moments for many-particle
      systems is costly, this representation reduces the solution of moment hierarchies
      to a complexity comparable to solving a heat equation. At steady states, moment
      hierarchies for finite CRNs interpolate between low-order and high-order scaling
      regimes, which may be approximated separately by distributions similar to those
      for deficiency-zero networks and connected through matched asymptotic expansions.
      In CRNs with multiple stable or metastable steady states, boundedness of high
      order moments provides the starting condition for recursive solution downward to
      low-order moments, reversing the order usually used to solve moment hierarchies.
      A basis for a subset of network flows defined by having the same mean-regressing
      property as the flows in deficiency-zero networks gives the leading contribution
      to low-order moments in CRNs at general deficiency, in a 1/n expansion in large
      particle numbers. Our results give a physical picture of the different
      informational roles of mean-regressing and non-mean-regressing flows and clarify
      the dynamical meaning of deficiency not only for first-moment conditions but for
      all orders in fluctuations.

PMID- 29335681
TI  - NASH-RELATED CIRRHOSIS: AN OCCULT LIVER DISEASE BURDEN.

PMID- 29335682
TI  - Robust Dynamic Risk Prediction with Longitudinal Studies.
AB  - Providing accurate and dynamic age-specific risk prediction is a crucial step in
      precision medicine. In this manuscript, we introduce an approach for estimating
      the tau-year age-specific absolute risk directly via a flexible varying
      coefficient model. The approach facilitates the utilization of predictors varying
      over an individual's lifetime. By using a nonparametric inverse probability
      weighted kernel estimating equation, the age-specific effects of risk factors are
      estimated without requiring the specification of the functional form. The
      approach allows borrowing information across individuals of similar ages, and
      therefore provides a practical solution for situations where the longitudinal
      information is only measured sparsely. We evaluate the performance of the
      proposed estimation and inference procedures with numerical studies, and make
      comparisons with existing methods in the literature. We illustrate the
      performance of our proposed approach by developing a dynamic prediction model
      using data from the Framingham Study.

PMID- 29335683
TI  - Sex Differences in Salivary Parameters of Caries Susceptibility in Healthy
      Individuals.
AB  - PURPOSE: To investigate salivary parameters of caries susceptibility in men and
      women in order to identify potential variations due to sexual dimorphism.
      MATERIALS AND METHODS: A total of 46 female and 24 male patients, aged 18-40
      years, participated in this study. Unstimulated saliva was collected for the
      evaluation of flow rate, pH, secretory IgA, Snyder test scores, and Streptococcus
      mutans counts (confirmed by PCR assay). Statistical analysis included the Mann
      Whitney, Kruskal-Wallis and Bonferroni tests, one-way ANOVA, and the Spearman
      correlation at a 5% significance level, followed by a general linear model and
      multiple linear regressions. RESULTS: Female participants presented lower
      salivary pH values compared to males (p < 0.05), and different patterns of
      correlation among salivary parameters were found in men (p < 0.05) and women (p <
      0.001). When comparing the variables according to Snyder test scores in men and
      women, there was a significant difference for S. mutans levels in the male group,
      and for pH and IgA in the female group (p < 0.05). Gender was found to be a
      predictor of salivary flow (R2 = 0.05; p < 0.05) and pH (R2 = 0.16; p < 0.001).
      In the female group, multiple regression showed several predictors for salivary
      flow rate, pH, IgA and Snyder test scores (p < 0.05), whereas no predictor was
      found in the male group (p > 0.05). CONCLUSION: Different salivary patterns were
      observed in men and women, thus the implications of such findings for caries
      susceptibility require further investigation.

PMID- 29335684
TI  - Association Between Self-Perceived Oral Health and Clinical Indicators.
AB  - PURPOSE: To determine whether self-perceived oral health impact and satisfaction
      measure oral health in the same way as do clinical indicators in adults and older
      adults. MATERIALS AND METHODS: The population consisted of adult patients aged 20
      to 59 years receiving care at "Juan Pablo II" Health Care Centre and older adult
      patients aged 60 or more years from the home for the elderly "Virgen del Amor
      Hermoso", Lima, Peru. The indices Oral Impacts on Daily Performance (OIDP) and
      Oral Satisfaction Scale of 0-10 (OSS 0-10) were used to evaluate perceived impact
      of and satisfaction with oral health. In addition, the following internationally
      validated criteria established by the World Health Organization (WHO) were used
      as clinical indicators: Decayed-Missing-Filled Teeth (DMFT) Index, O'Leary's
      Hygiene Index, Community Periodontal Index, Motivation to Hygiene Index, Denture
      Situation Index, Need for Denture Index, Denture Hygiene Index and Oral Mucosal
      Lesion Index. RESULTS: Forty-four adults and 53 older adults participated. OIDP
      showed that the greatest perceived difficulty in daily performance was "eating
      and enjoying food" (adults: 77.3% and older adults: 79.2%). The OSS 0-10 showed
      that among adults, 43.1% were dissatisfied, 20.5% were neutral and 36.4% were
      satisfied, while among older adults, 45.3% were dissatisfied, 22.6% were neutral
      and 32.1% were satisfied. A statistically significant association was found
      between OSS 0-10 and 1. DMFT index in adults; 2. upper denture situation in older
      adults; and 3. denture hygiene in older adults. A highly significant inverse
      linear correlation was found between OIDP and OSS 0-10 in adults and older
      adults. CONCLUSION: The perceived impact of oral health does not have a
      demonstrable association with oral health problems when used as an instrument for
      measuring oral health status, whereas perceived satisfaction with oral health has
      a better association with the clinical indicators.

PMID- 29335685
TI  - Can Coloured Fluoride Gel Stain Demineralised Enamel?
AB  - PURPOSE: This study evaluated the colour changes of demineralized enamel after
      treatment with coloured fluoride gel. MATERIALS AND METHODS: Enamel blocks
      obtained from bovine incisors were submitted to artificial caries induction by pH
      cycling followed by fluoride gel applications (2% sodium fluoride, pH 6.8) using
      a colourless gel (control group), pink or blue gels. The enamel optical
      properties were evaluated by spectrophotometry, using the CIE L*a*b* system at
      baseline (sound enamel), after artificial caries induction (demineralised enamel)
      and after each of the five fluoride gel applications (weekly intervals). Changes
      in enamel optical properties (DeltaE) were analysed by two-way ANOVA and Tukey's
      test (alpha = 0.05). RESULTS: No significant differences were found among
      fluoride gels (p = 0.476) regardless of the presence of pigments in the gel.
      DeltaE values were significantly different (p < 0.001) between baseline
      evaluation and treated enamel (after fluoride gel application). CONCLUSION: This
      in vitro study demonstrated that colour changes in enamel do not occur during
      fluoride gel treatment, regardless of the presence or absence of coloured
      pigments in the gel.

PMID- 29335686
TI  - Synthetic Hydroxyapatite as a Biomimetic Oral Care Agent.
AB  - PURPOSE: Human tooth enamel consists mostly of minerals, primarily
      hydroxyapatite, Ca10(PO4)6(OH)2, and thus synthetic hydroxyapatite can be used as
      a biomimetic oral care agent. This review describes the synthesis and
      characterization of hydroxyapatite from a chemist's perspective and provides an
      overview of its current use in oral care, with a focus on dentin
      hypersensitivity, caries, biofilm management, erosion, and enamel lesions.
      SOURCES: Reviews and original research papers published in English and German
      were included. RESULTS: The efficiency of synthetic hydroxyapatite in occluding
      open dentin tubules, resulting in a protection for sensitive teeth, has been well
      documented in a number of clinical studies. The first corresponding studies on
      caries, biofilm management and erosion have provided evidence for a positive
      effect of hydroxyapatite either as a main or synergistic agent in oral care
      products. However, more in situ and in vivo studies are needed due to the
      complexity of the oral milieu and to further clarify existing results.
      CONCLUSIONS: Due to its biocompatibility and similarity to biologically formed
      hydroxyapatite in natural tooth enamel, synthetic hydroxyapatite is a promising
      biomimetic oral care ingredient that may extend the scope of preventive
      dentistry.

PMID- 29335687
TI  - Structure of the Bacterial Community in Different Stages of Early Childhood
      Caries.
AB  - PURPOSE: To characterise in vivo the structure of bacterial communities in
      decayed and sound primary teeth. MATERIALS AND METHODS: Samples of biofilms were
      collected from three groups of patients with complete and exclusively primary
      dentition (n = 45): G1: sound teeth (n = 15); G2: enamel lesion (n = 15); G3:
      dentin lesion (n = 15). DNA was extracted (CTAB 2%) from the biofilm, the partial
      16S rRNA gene was amplified with Bacteria Universal Primers (BA338fGC - UN518r)
      and subjected to DGGE (denaturing gradient gel electrophoresis). Multidimensional
      scaling and ANOSIM (analysis of similarity) were employed to determine the
      structure of the bacterial communities. The amplicon richness was determined by
      averaging amplicons, with the differences between treatments determined with
      ANOVA, while means were compared using Tukey's test (p < 0.05). RESULTS: Compared
      to sound teeth, a greater variety of bacterial communities was found in decayed
      teeth. Despite the differences between the bacterial communities of sound teeth
      and decayed teeth, the Venn diagram showed that the samples had 38 amplicons in
      common. Greater amplicon richness was observed in samples of decayed teeth
      (enamel: 20.5 +/- 2.7; dentin: 20.1 +/- 2.8) compared with the sound samples
      (12.0 +/- 4.3) (p <0.05), indicating enhanced growth for specific groups of
      bacteria on decayed teeth. CONCLUSION: Although there is less bacterial diversity
      on sound than ECC-decayed teeth, the bacterial communities are very similar.

PMID- 29335688
TI  - Multiple invasive cervical resorption and celiac disease: A case report.
AB  - Multiple invasive cervical resorption (MICR) is a rare disease of unknown
      etiology. A case of a patient with MICR of six teeth, with low vitamin D3 level
      detected, is presented. Applied surgical and general treatments were only
      partially effective, as they failed to stop the resorption, although the
      parameters of calcium-phosphate management appreciably improved, and secondary
      hyperparathyroidism was successfully resolved.

PMID- 29335689
TI  - Psoriasis: A review of systemic comorbidities and dental management
      considerations.
AB  - OBJECTIVE: There is a growing body of evidence to substantiate that cutaneous
      psoriasis is associated with an increased risk for a multitude of systemic
      disorders. Although there is an extensive array of medical publications regarding
      psoriasis, the dental literature has almost exclusively been focused on erythema
      migrans and occasionally, with oral psoriatic mucositis, chronic periodontitis,
      and psoriatic arthritis of the temporomandibular joint. This report will review
      the diversity of systemic comorbidities, namely cardiovascular, neurologic,
      renal, liver, gastrointestinal, pulmonary, endocrine, ocular, arthritic
      (including temporomandibular joint), nail, cutaneous, and psychologic (including
      suicide) disorders; neoplasia; infection; dyslipidemia; vitamin D deficiency;
      substance abuse; higher mortality; and oral mucosal involvement. A discussion of
      the oral and maxillofacial relevance of these comorbidities is also provided.
      METHOD AND MATERIALS: The author conducted a PubMed search from 1975 through
      August 2017 for articles on comorbidities associated with psoriasis. For select
      topics, some relevant case reports were examined. RESULTS: A search on PubMed
      yielded almost 44,000 articles on psoriasis and nearly 1,300 with the keywords
      psoriasis and comorbidities. Articles selected for discussion consisted mostly of
      recent systematic reviews and meta-analyses. Case reports were included when
      there was a restricted number of psoriatic patients with a particular
      comorbidity. CONCLUSION: When a patient presents with a history of psoriasis, the
      dental practitioner should expand the medical history process to ascertain
      possible correlated diseases. Information gleaned from this interview process may
      prompt the attending dental clinician to seek consultation with the patient's
      physician to gain greater insight to the severity of any prevailing comorbidities
      and engage in discussions for possible modifications in dental management.
      Knowledge of psoriatic comorbidities and their possible impact on dental care may
      improve clinical outcomes.

PMID- 29335690
TI  - Ni(OH)2-Fe2P hybrid nanoarray for alkaline hydrogen evolution reaction with
      superior activity.
AB  - It is highly attractive to develop efficient hydrogen evolution reaction (HER)
      electrocatalysts under alkaline conditions. In this communication, we report the
      preparation of amorphous Ni(OH)2 decorated Fe2P nanoarray on Ti mesh (Ni(OH)2
      Fe2P/TM) via electrodeposition. As a 3D electrode for the hydrogen evolution
      reaction, such Ni(OH)2-Fe2P/TM demonstrates superior catalytic activity.
      Moreover, the as-prepares electrocatalyst requires an overpotential of only 76 mV
      to drive a current density of 10 mA cm-2, which is 94 mV less than that for
      Fe2P/TM. It also shows strong long-term electrochemical durability with its
      catalytic activity being maintained for at least 20 h.

PMID- 29335691
TI  - Size-dependent formation of membrane nanotubes: continuum modeling and molecular
      dynamics simulations.
AB  - Membrane nanotubes play important functional roles in numerous cell activities
      such as cellular transport and communication. By exerting an external pulling
      force over a finite region in a membrane patch, here we investigate the size
      dependence of the membrane nanotube formation under the continuum and atomistic
      modeling frameworks. It is shown that the membrane undergoes a discontinuous
      shape transition as the size of the pulling region and the membrane tension
      increase. A formula characterizing the nonlinear relationship between the maximum
      static pulling force and pulling size is identified. During the membrane
      extraction, lipids in the upper and lower leaflets exhibit different behaviors of
      structural rearrangements. Moreover, our computational simulations indicate that
      the steady state pulling force increases linearly with the pulling velocity as
      well as the size of the pulling region.

PMID- 29335692
TI  - Marine natural products.
AB  - Covering: 2016. Previous review: Nat. Prod. Rep., 2017, 34, 235-294This review
      covers the literature published in 2016 for marine natural products (MNPs), with
      757 citations (643 for the period January to December 2016) referring to
      compounds isolated from marine microorganisms and phytoplankton, green, brown and
      red algae, sponges, cnidarians, bryozoans, molluscs, tunicates, echinoderms,
      mangroves and other intertidal plants and microorganisms. The emphasis is on new
      compounds (1277 in 432 papers for 2016), together with the relevant biological
      activities, source organisms and country of origin. Reviews, biosynthetic
      studies, first syntheses, and syntheses that led to the revision of structures or
      stereochemistries, have been included.

PMID- 29335693
TI  - Crystal structures of uranyl complexes with isobutyrate and isovalerate anions.
AB  - Single crystals of Na[(UO2)(i-C3H7COO)3].0.7H2O (I), Cs[(UO2)(i-C3H7COO)3] (II)
      and (NH4)[(UO2)(i-C4H9COO)3] (III) were obtained via isothermal evaporation and
      their structures were solved using X-ray diffraction techniques. Even though the
      ligands are branched, bulky and spatial, many carbon and hydrogen atoms are still
      disordered in these crystal structures at low temperature. A new type of Na
      coordination is observed for the first time for this family of compounds,
      proposing high sensitivity of compound I to humidity. Depolymerization of the
      metal-oxygen frameworks for the new compounds is compared with the known ones.
      Coordination sequences of sodium/cesium and uranyl complexes with aliphatic
      monocarboxylate ions are calculated to show different crystal-chemical function
      of crystallographically independent atoms. As there are analogous compounds to
      the title ones with straight-chain ligands, such groups of similar compounds with
      single varying parameters are very advantageous for establishing correlations
      between composition and crystal structure.

PMID- 29335694
TI  - The Seventh Biennial Berry Health Benefits Symposium.
AB  - Research advancing current scientific understanding of the health benefits of
      berries continues to increase. The Berry Health Benefits Symposium (BHBS) is a
      biennial meeting highlighting the most recent berry health benefits research from
      all over the world. Pismo Beach, California was the venue for the seventh
      biennial BHBS in 2017, and featured oral invited papers on heart health and
      healthy aging, gut/microbiome health, brain aging, inflammation, cancer
      prevention, berry special topics, technology and chemistry. These thematic health
      areas, while not exhaustive, characterize the state of berry health benefits
      science. The advancing field now encompasses human efficacy trials along with the
      most recent animal model and cell culture work elucidating mechanisms of action.
      Similar to past meetings, the research findings at the 2017 BHBS primarily
      focused on blackberries, blueberries, red raspberries, black raspberries,
      cranberries, and strawberries. However, research on other berry fruits, such as
      chokeberry (aronia berry), cloudberry, and bilberry were also covered. The BHBS
      continues to be a leading forum for interactions between scientists and berry
      industry stakeholders. The cluster of papers in this issue represents a snapshot
      of presentations at the 2017 BHBS, which support the positive biological effects
      of berries on human health and disease risk reduction.

PMID- 29335695
TI  - Synthesis of garlic skin-derived 3D hierarchical porous carbon for high
      performance supercapacitors.
AB  - A three-dimensional hierarchical porous carbon is synthesized via a facile
      chemical activation route with garlic skin as the precursor and KOH as the
      activating agent. The as-obtained carbon presents a high specific surface area of
      2818 m2 g-1 and a hierarchical porous architecture containing macroporous
      frameworks, mesopores (2-4 nm), and micropores (0.6-1.0 nm). As the electrode
      material for a supercapacitor, due to its unique interconnected porous structure,
      this garlic skin-derived carbon exhibits excellent electrochemical performance
      and cycling stability. At a current density of 0.5 A g-1, the capacitance is up
      to 427 F g-1 (162 F cm-3). Even at a high current density of 50 A g-1, the
      capacitance can be maintained to a high value of 315 F g-1 (120 F cm-3). After
      charging-discharging at a current density of 4.5 A g-1 for 5000 cycles, the
      capacitance retention is as high as 94%. The results suggest that this garlic
      skin-derived 3D hierarchical porous carbon is a promising electrode material for
      high-performance supercapacitors.

PMID- 29335696
TI  - Structurally and electronically modulated spin interaction of transient
      biradicals in two photon-gated stepwise photochromism.
AB  - The development of two-photon induced photochromic compounds is important for
      advanced photoresponsive materials. The utilization of the long-lived transient
      states or species for two-photon absorption is one of the efficient strategies to
      realize the advanced photochemical behavior beyond a one-photon photochemical
      reaction. We have synthesized bi-photochromic compounds composed of two
      photochromic phenoxyl-imidazolyl radical complex units. The biphotochromic
      compounds generate two biradical units when the two photochromic units absorb
      photons with a stepwise manner. The interaction between the two biradicals
      through the central bridging phenyl ring is the key feature to control the
      stepwise photochromic reaction. Here, we introduced aromatic spacers in order to
      modulate the distance and the dihedral angle between the biradical units. The
      color and the rate of the thermal back reaction of the stepwise photochromism can
      be regulated by the control of the central bridging part. These results give
      important insights to develop desirable advanced photoresponsive compounds.

PMID- 29335697
TI  - Photodissociation dynamics of bromoiodomethane from the first and second
      absorption bands. A combined velocity map and slice imaging study.
AB  - The photodissociation dynamics of bromoiodomethane (CH2BrI) have been
      investigated at the maximum of the first A and second A' absorption bands, at 266
      and 210 nm excitation wavelengths, respectively, using velocity map and slice
      imaging techniques in combination with a probe detection of both iodine and
      bromine fragments, I(2P3/2), I*(2P1/2), Br(2P3/2) and Br*(2P1/2) via (2 + 1)
      resonance enhanced multiphoton ionization. Experimental results, i.e.
      translational energy and angular distributions, are reported and discussed in
      conjunction with high level ab initio calculations of potential energy curves and
      absorption spectra. The results indicate that in the A-band, direct dissociation
      through the 5A' excited state leads to the I(2P3/2) channel while I*(2P1/2) atoms
      are produced via the 5A' -> 4A'/4A'' nonadiabatic crossing. The presence of Br
      and Br* fragments upon excitation to the A-band is attributed to indirect
      dissociation via a curve crossing between the 5A' with upper excited states such
      as the 9A'. The A'-band is characterized by a strong photoselectivity leading
      exclusively to the Br(2P3/2) and Br*(2P1/2) channels, which are likely produced
      by dissociation through the 9A' excited state. Avoided crossings between several
      excited states from both the A and A' bands entangle however the possible
      reaction pathways.

PMID- 29335699
TI  - Michael addition of carbonyl compounds to nitroolefins under the catalysis of new
      pyrrolidine-based bifunctional organocatalysts.
AB  - Novel bifunctional pyrrolidine-based organocatalysts for the asymmetric Michael
      addition of carbonyl compounds to nitroolefins have been synthesised from
      homoallylamines, which are easily obtained from (R)-glyceraldehyde as a chiral
      precursor. Under optimal reaction conditions, these bifunctional organocatalysts
      showed a high catalytic efficiency (almost quantitative yield in most cases) and
      stereoselectivity in the Michael addition reactions of a variety of aldehydes (up
      to 98 : 2 dr and 97% ee) and ketones (up to 98 : 2 dr and 99% ee) to
      nitroolefins.

PMID- 29335698
TI  - Absorbance enhancement of aptamers/GNP enables sensitive protein detection in rat
      brains.
AB  - An absorbance enhanced probe based on gold nanoparticles (GNPs) was proposed for
      a protein assay in the cerebrospinal fluid of a rat brain. The GNPs, assembled
      with two aptamers by proximity ligation, have high anti-salt properties, and good
      selectivity and response toward proteins, such as interferon-gamma, in the brain.

PMID- 29335701
TI  - A mononuclear manganese(iii)-hydroperoxo complex: synthesis by activating
      dioxygen and reactivity in electrophilic and nucleophilic reactions.
AB  - We report the synthesis of manganese(iii)-peroxo (MnIII(O2)) and manganese(iii)
      hydroperoxo (MnIII(O2H)) complexes by activating dioxygen (O2) and the amphoteric
      reactivity of the Mn(iii)-hydroperoxo complex in electrophilic and nucleophilic
      reactions.

PMID- 29335702
TI  - Ultrasmall Sn nanoparticles embedded in spherical hollow carbon for enhanced
      lithium storage properties.
AB  - We here report on the preparation and Li-ion battery anode application of
      ultrasmall Sn nanoparticles (~5 nm) uniformly embedded in spherical hollow
      carbon. The novel Sn-C composite shows a high Li-storage capacity (743 mA h g-1
      at 0.5 A g-1) with unprecedentedly high cyclic stability (92.1% capacity
      retention after 6000 cycles at 4 A g-1).

PMID- 29335704
TI  - Photoexcited charge carrier dynamics of interconnected TiO2 nanoparticles:
      evidence of enhancement of charge separation at anatase-rutile particle
      interfaces.
AB  - The charge carrier kinetics of hydrothermally treated TiO2 nanoparticles,
      consisting of interconnected anatase and rutile crystallographic forms, was
      investigated using a heterodyne transient grating technique to obtain direct
      evidence of the enhancement of charge separation efficiency. We found that
      surface recombination arising from trapped electrons was retarded, compared with
      that of P25 TiO2 nanoparticles, with the aid of an increase of particle
      interfaces. This means that the charge separation efficiency of hydrothermally
      treated TiO2 nanoparticles is higher than that of P25 TiO2 nanoparticles, to
      which the enhanced photocatalytic performance of the hydrothermally treated TiO2
      nanoparticles could be attributed.

PMID- 29335705
TI  - Synthesis of 2,5-disubstituted oxazoles via cobalt(iii)-catalyzed cross-coupling
      of N-pivaloyloxyamides and alkynes.
AB  - An efficient synthesis of 2,5-disubstituted oxazoles via Co(iii) catalysis is
      described herein. The synthesis is achieved under mild conditions through [3+2]
      cycloaddition of N-pivaloyloxyamides and alkynes. The reaction operates through
      an internal oxidation pathway and features a very broad substrate scope. The one
      step synthesis of natural products such as texamine and balsoxin has been
      demonstrated via this protocol.

PMID- 29335709
TI  - Elongated phase separation domains in spin-cast polymer blend thin films
      characterized using a panoramic image.
AB  - Polymer thin films with micro/nano-structures can be prepared by a solvent
      evaporation induced phase separation process via spin-casting a polymer blend,
      where the elongated phase separation domains are always inevitable. The striation
      defect, as a thickness nonunifomity in spin-cast films, is generally coexistent
      with the elongated domains. Herein, the morphologies of polymer blend thin films
      are recorded from the spin-cast center to the edge in a panoramic view. The
      elongated domains are inclined to appear at the ridge regions of striations with
      increasing radial distance and align radially, exhibiting a coupling between the
      phase separation morphology and the striation defect that may exist. We
      demonstrate that the formation of elongated domains is not attributed to shape
      deformation, but is accomplished in situ. A possible model to describe the
      initiation and evolution of the polymer blend phase separation morphology during
      spin-casting is proposed.

PMID- 29335711
TI  - White Blood Cell BRCA1 Promoter Methylation Status and Ovarian Cancer Risk: A
      Perspective.

PMID- 29335710
TI  - Continuous-flow trapping and localized enrichment of micro- and nano-particles
      using induced-charge electrokinetics.
AB  - In this work, we report an effective microfluidic technique for continuous-flow
      trapping and localized enrichment of micro- and nano-particles by using induced
      charge electrokinetic (ICEK) phenomena. The proposed technique utilizes a simple
      microfluidic device that consists of a straight microchannel and a conducting
      strip attached to the bottom wall of the microchannel. Upon application of the
      electric field along the microchannel, the conducting strip becomes polarized to
      introduce two types of ICEK phenomena, the ICEK flow vortex and particle
      dielectrophoresis, and they are identified by a theoretical model formulated in
      this study to be jointly responsible for the trapping of particles over the edge
      of the conducting strip. Our experiments showed that successful trapping requires
      an AC/DC combined electric field: the DC component is mainly to induce
      electroosmotic flow for transporting particles to the trapping location; the AC
      component induces ICEK phenomena over the edge of the conducting strip for
      particle trapping. The performance of the technique is examined with respect to
      the applied electric voltage, AC frequency and the particle size. We observed
      that the trapped particles form a narrow band (nearly a straight line) defined by
      the edge of the conducting strip, thereby allowing localized particle enrichment.
      For instance, we found that under certain conditions a high particle enrichment
      ratio of 200 was achieved within 30 seconds. We also demonstrated that the
      proposed technique was able to trap particles from several microns down to
      several tens of nanometer. We believe that the proposed ICEK trapping would have
      great flexibility that the trapping location can be readily varied by controlling
      the location of the patterned conducting strip and multiple-location trapping can
      be expected with the use of multiple conducting strips.

PMID- 29335712
TI  - White Blood Cell BRCA1 Promoter Methylation Status and Ovarian Cancer Risk.
AB  - Background: The role of normal tissue gene promoter methylation in cancer risk is
      poorly understood. Objective: To assess associations between normal tissue BRCA1
      methylation and ovarian cancer risk. Design: 2 case-control (initial and
      validation) studies. Setting: 2 hospitals in Norway (patients) and a population
      based study (control participants). Participants: 934 patients and 1698 control
      participants in the initial study; 607 patients and 1984 control participants in
      the validation study. Measurements: All patients had their blood sampled before
      chemotherapy. White blood cell (WBC) BRCA1 promoter methylation was determined by
      using methylation-specific quantitative polymerase chain reaction, and the
      percentage of methylation-positive samples was compared between population
      control participants and patients with ovarian cancer, including the subgroup
      with high-grade serous ovarian cancer (HGSOC). Results: In the initial study,
      BRCA1 methylation was more frequent in patients with ovarian cancer than control
      participants (6.4% vs. 4.2%; age-adjusted odds ratio [OR], 1.83 [95% CI, 1.27 to
      2.63]). Elevated methylation, however, was restricted to patients with HGSOC
      (9.6%; OR, 2.91 [CI, 1.85 to 4.56]), in contrast to 5.1% and 4.0% of patients
      with nonserous and low-grade serous ovarian cancer (LGSOC), respectively. These
      findings were replicated in the validation study (methylation-positive status in
      9.1% of patients with HGSOC vs. 4.3% of control participants-OR, 2.22 [CI 1.40 to
      3.52]-4.1% of patients with nonserous ovarian cancer, and 2.7% of those with
      LGSOC). The results were not influenced by tumor burden, storage time, or WBC
      subfractions. In separate analyses of young women and newborns, BRCA1 methylation
      was detected in 4.1% (CI, 1.8% to 6.4%) and 7.0% (CI, 5.0% to 9.1%),
      respectively. Limitations: Patients with ovarian cancer were recruited at the
      time of diagnosis in a hospital setting. Conclusion: Constitutively normal tissue
      BRCA1 promoter methylation is positively associated with risk for HGSOC. Primary
      Funding Source: Norwegian Cancer Society.

PMID- 29335713
TI  - Risk for Arterial and Venous Thrombosis in Patients With Myeloproliferative
      Neoplasms: A Population-Based Cohort Study.
AB  - Background: Patients with myeloproliferative neoplasms (MPNs) are reported to be
      at increased risk for thrombotic events. However, no population-based study has
      estimated this excess risk compared with matched control participants. Objective:
      To assess risk for arterial and venous thrombosis in patients with MPNs compared
      with matched control participants. Design: Matched cohort study. Setting:
      Population-based setting in Sweden from 1987 to 2009, with follow-up to 2010.
      Patients: 9429 patients with MPNs and 35 820 matched control participants.
      Measurements: The primary outcomes were rates of arterial and venous thrombosis.
      Flexible parametric models were used to calculate hazard ratios (HRs) and
      cumulative incidence with 95% CIs. Results: The HRs for arterial thrombosis among
      patients with MPNs compared with control participants at 3 months, 1 year, and 5
      years were 3.0 (95% CI, 2.7 to 3.4), 2.0 (CI, 1.8 to 2.2), and 1.5 (CI, 1.4 to
      1.6), respectively. The corresponding HRs for venous thrombosis were 9.7 (CI, 7.8
      to 12.0), 4.7 (CI, 4.0 to 5.4), and 3.2 (CI, 2.9 to 3.6). The rate was
      significantly elevated across all age groups and was similar among MPN subtypes.
      The 5-year cumulative incidence of thrombosis in patients with MPNs showed an
      initial rapid increase followed by gentler increases during follow-up. The HR for
      venous thrombosis decreased during more recent calendar periods. Limitation: No
      information on individual laboratory results or treatment. Conclusion: Patients
      with MPNs across all age groups have a significantly increased rate of arterial
      and venous thrombosis compared with matched control participants, with the
      highest rates at and shortly after diagnosis. Decreases in the rate of venous
      thrombosis over time likely reflect advances in clinical management. Primary
      Funding Source: The Cancer Research Foundations of Radiumhemmet,
      Blodcancerfonden, the Swedish Research Council, the regional agreement on medical
      training and clinical research between Stockholm County Council and Karolinska
      Institutet, the Adolf H. Lundin Charitable Foundation, and Memorial Sloan
      Kettering Cancer Center.

PMID- 29335714
TI  - Guideline: Experts recommend a single dose of oral steroids for pain relief in
      acute sore throat.

PMID- 29335715
TI  - In postmenopausal women with osteoporosis, romosozumab followed by alendronate
      reduced fractures vs alendronate alone.

PMID- 29335716
TI  - Pooled RCTs: In postmenopausal women, hormone therapy for 6 to 7 years did not
      affect mortality at 18 years.

PMID- 29335717
TI  - Pooled RCTs: Reanalysis accounting for screening intensity suggests that
      screening reduces prostate cancer mortality.

PMID- 29335718
TI  - Adding patent foramen ovale closure to antiplatelet drugs reduced ischemic stroke
      after cryptogenic stroke.

PMID- 29335719
TI  - Adding patent foramen ovale closure to antiplatelet therapy reduced stroke after
      cryptogenic stroke.

PMID- 29335720
TI  - Review: Newer second-line drugs for diabetes are not more cost-effective than
      sulfonylureas.

PMID- 29335721
TI  - Review: In suspected influenza, some rapid tests have high sensitivity and high
      specificity for detecting infection.

PMID- 29335722
TI  - Review: In adults, contrast-enhanced CT is not linked to acute kidney injury or
      mortality vs noncontrast CT.

PMID- 29335724
TI  - Correction: Benefits and Harms of Intensive Blood Pressure Treatment in Adults
      Aged 60 Years or Older.

PMID- 29335723
TI  - Review: In primary care, CRP testing, shared decision making, and procalcitonin
      reduce antibiotic prescribing for ARI.

PMID- 29335725
TI  - Growth and Rupture Risk of Small Unruptured Intracranial Aneurysms.

PMID- 29335726
TI  - Growth and Rupture Risk of Small Unruptured Intracranial Aneurysms.

PMID- 29335727
TI  - Presence of Human Hepegivirus-1 in a Cohort of People Who Inject Drugs.

PMID- 29335728
TI  - Presence of Human Hepegivirus-1 in a Cohort of People Who Inject Drugs.

PMID- 29335729
TI  - Presence of Human Hepegivirus-1 in a Cohort of People Who Inject Drugs.

PMID- 29335731
TI  - Changes in Hospital-Physician Affiliations in U.S. Hospitals.

PMID- 29335730
TI  - Changes in Hospital-Physician Affiliations in U.S. Hospitals.

PMID- 29335732
TI  - Changes in Hospital-Physician Affiliations in U.S. Hospitals.

PMID- 29335733
TI  - Changes in Hospital-Physician Affiliations in U.S. Hospitals.

PMID- 29335734
TI  - Two Doctors Meet.

PMID- 29335735
TI  - Let the Sun Shine In! An Adventure in Open Payments.

PMID- 29335736
TI  - Web Exclusives. Annals for Hospitalists Inpatient Notes - Modernizing Rounds-Why
      It's Time to Redesign Our Hospital Practice.

PMID- 29335737
TI  - Shedding New Light on the Magnitude of Thrombosis Risk in Patients With
      Myeloproliferative Neoplasms.

PMID- 29335738
TI  - Remission of Psoriasis After Treatment of Chronic Hepatitis C Virus Infection
      With Direct-Acting Antivirals.

PMID- 29335739
TI  - A Postzygotic SMO Mutation Caused the Original Case of Happle-Tinschert Syndrome.

PMID- 29335740
TI  - Painful Papules on the Hand: A Quiz.

PMID- 29335741
TI  - Methotrexate Treatment for Pityriasis Rubra Pilaris: A Case Series and Literature
      Review.
AB  - Treatment recommendations for pityriasis rubra pilaris (PRP) are based solely on
      case reports and small case series, as to-date no randomized controlled trials
      are available. We present here a case series of 3 patients and a literature
      review of 28 studies treating a total of 116 patients, with the aim of providing
      data regarding efficacy and safety of methotrexate in the treatment of PRP.
      Methotrexate was effective in our patients; the review showed an overall response
      rate of 65.5% with complete clearing in 23.3% and excellent improvement in 17.2%,
      respectively. After excluding studies with other concurrent systemic therapies or
      low reliability, the overall response rate increased to 90.9%, with complete
      clearing in 40.9% and excellent improvement in 31.8%, respectively. Sixteen
      adverse reactions, of which 11 were mild, were observed in 15 patients (12.9%).
      In conclusion, the available literature supports good response rates and safety
      of methotrexate in PRP.

PMID- 29335742
TI  - Stand-alone Emollient Treatment Reduces Flares After Discontinuation of Topical
      Steroid Treatment in Atopic Dermatitis: A Double-blind, Randomized, Vehicle
      controlled, Left-right Comparison Study.
AB  - Prevention of the flares is a main goal in the long-term treatment of atopic
      dermatitis (AD). Therefore we investigated the efficacy of a water-in-oil
      emollient, containing licochalcone A, omega-6-fatty acids, ceramide 3 and
      glycerol, for prevention of the flares in adults with mild to moderately severe
      AD, treated with topical steroids, that led to clearing of the inflammatory
      lesions and had been discontinued prior to inclusion. The study was a 12-week,
      double-blind, randomized, vehicle-controlled, left-right comparison test with the
      number of relapses, defined as re-occurrence of erythema for at least 3
      consecutive days, considered the primary outcome. Compared with the vehicle, the
      active formulation significantly reduced the number of relapses and maintained
      the barrier homeostasis of the respective arm. To the best of knowledge, this is
      the first study to show prevention of the AD flares by the use of stand-alone
      emollient treatment, based on comparison with the corresponding vehicle while
      excluding concomitant/rescue medications.

PMID- 29335744
TI  - [National Competency-Based Learning Objective Catalogue for Dental and Human
      Medicine].

PMID- 29335745
TI  - [Health privacy in the age of digital networks].
AB  - Digitization in the health sector embodies opportunities and risks. These consist
      of patient and data confidentiality. Vulnerability of data concerning integrity
      and availability can lead to financial losses and to damage of the health of data
      subjects. Those risks must be tackled by privacy or data protection law. For this
      purpose we have the European Data Protection Regulation as a comprehensive legal
      framework and a harmonizing bracket.This framework contains regulations on
      consent, purpose binding and data transfer, on rights of the data subject,
      technical and organizational measures and procedural arrangements. Recently,
      codes of conduct and certification schemes have been added as instruments. The
      frame of privacy law is completed by the law on medical products and information
      security regulations.Unfortunately, German legislation did not grip the
      opportunity of the European regulation to modernize, tighten and harmonize
      national privacy law in the health sector. This led to a lack of clarity,
      particularly because of the parallel applicability of privacy law and
      professional law. Central issues - for instance concerning transparency for data
      subjects, official supervision, analytics and processing for research purposes -
      remain dysfunctional. The German legislation should adjust those deficits.
      Corporations and the chambers for health professionals could and should also be
      active for this concern.

PMID- 29335746
TI  - [Cockade of the cecum in a child with acute abdominal pain].

PMID- 29335743
TI  - [Prevention of cardiovascular diseases].
AB  - The incidence of cardiovascular diseases can be reduced by the early detection
      and targeted treatment of risk factors and subclinical forms of the disease.
      Primary prevention provides several opportunities for successful interventions.
      In addition to a drug-based therapy, especially life style-modifying measures,
      such as physical activity, normalization of body weight, consistent nicotine
      abstinence and the consideration of psychosocial aspects represent core
      components of prevention programs. Healthcare data indicate that risk factors
      still often remain undetected and that the full potential of risk factor
      management has not yet been fully exploited at a population level. Especially
      motivation of patients and adherence to therapy represent key elements of
      successful prevention efforts.

PMID- 29335747
TI  - Patellar resurfacing versus patellar retention in primary total knee
      arthroplasty: a systematic review of overlapping meta-analyses.
AB  - PURPOSE: The need of patellar resurfacing in total knee arthroplasty (TKA) is a
      subject of debate. This systematic review of overlapping meta-analyses aimed to
      assess and analyze current evidence regarding patellar resurfacing and non
      resurfacing in TKA. METHODS: A systematic literature search was performed in
      March 2017 in PubMed, CINAHL and Cochrane Library. Inclusion criteria were meta
      analysis of randomized controlled trials that compared TKA with and without
      patellar resurfacing considering as outcomes re-operations rate, complications,
      anterior knee pain, functional scores. The quality of meta-analyses was evaluated
      with AMSTAR score and the most relevant meta-analysis was determined by applying
      the Jadad algorithm. RESULTS: Ten meta-analyses, published between 2005 and 2015,
      were included in the systematic review. Two studies found a significantly
      increased Knee Society Score in the resurfacing group. According to four meta
      analyses, anterior knee pain incidence was lower in resurfacing group. Six of the
      included studies described a greater risk of re-intervention in the non
      resurfacing groups. The overall quality of included studies was moderate. The
      most relevant meta-analysis reported no differences in functional scores and
      incidence of anterior knee pain between the groups. CONCLUSIONS: Comparable
      outcomes were found when comparing patellar resurfacing and non-resurfacing in
      TKA. The higher risk of re-operations after non-resurfacing should be interpreted
      with caution due to the methodological limitations of the meta-analyses regarding
      search criteria, heterogeneity and the inherent bias of easier indication to
      reoperation when the patella is not resurfaced. There is no clear superiority of
      patellar resurfacing compared to patellar retention. LEVEL OF EVIDENCE: Level II,
      systematic review of meta-analyses.

PMID- 29335748
TI  - Hydrogel implant is as effective as osteochondral autologous transplantation for
      treating focal cartilage knee injury in 24 months.
AB  - PURPOSE: The treatment approach for a patient with knee joint focal cartilage
      lesion is a difficult decision. To date, there has been no randomized clinical
      trial involving Hydrogel (CartivaTM). This study evaluated and compared the
      results of a hydrogel implant (CartivaTM) with autologous osteochondral
      transplantation (AOT) for treating knee joint focal cartilage lesions. METHODS:
      Thirty-eight symptomatic patients, with a focal cartilage lesion of Outerbridge
      grades III or IV, were randomized into one of two groups according to the
      inclusion and exclusion criteria. Group I underwent AOT, and Group II was treated
      with a Hydrogel implant. Patients were evaluated preoperatively and again
      postoperatively at 6, 12, and 24 months using the subjective International Knee
      Documentation Committee (IKDC) scores, Visual Analog Scale for Pain (VAS Pain),
      Activities of Daily Living Scale (ADLS) and Lysholm score. RESULTS: Both groups
      showed significant improvements from baseline (pre-surgery) to post-surgery (6,
      12, and 24 months; p < 0.05), but there was no difference between the groups.
      Regarding complications, prolonged pain was observed in four patients (10.5%),
      two from each group, with a regression of symptoms within 1 year. CONCLUSION: The
      Hydrogel implant showed similar efficiency as the autologous osteochondral graft
      for treating knee joint focal cartilage lesions. Both techniques showed
      satisfactory results compared to preoperative status. The Hydrogel implant was
      safe and effective, and it provided good stability and joint function at 2-year
      follow-up. LEVEL OF EVIDENCE: I.

PMID- 29335750
TI  - Performance drifts in two-finger cyclical force production tasks performed by one
      and two actors.
AB  - We explored changes in the cyclical two-finger force performance task caused by
      turning visual feedback off performed either by the index and middle fingers of
      the dominant hand or by two index fingers of two persons. Based on an earlier
      study, we expected drifts in finger force amplitude and midpoint without a drift
      in relative phase. The subjects performed two rhythmical tasks at 1 Hz while
      paced by an auditory metronome. One of the tasks required cyclical changes in
      total force magnitude without changes in the sharing of the force between the two
      fingers. The other task required cyclical changes in the force sharing without
      changing total force magnitude. Subjects were provided with visual feedback,
      which showed total force magnitude and force sharing via cursor motion along the
      vertical and horizontal axes, respectively. Further, visual feedback was turned
      off, first on the variable that was not required to change and then on both
      variables. Turning visual feedback off led to a mean force drift toward lower
      magnitudes while force amplitude increased. There was a consistent drift in the
      relative phase in the one-hand task with the index finger leading the middle
      finger. No consistent relative phase drift was seen in the two-person tasks. The
      shape of the force cycle changed without visual feedback reflected in the lower
      similarity to a perfect cosine shape and in the higher time spent at lower force
      magnitudes. The data confirm findings of earlier studies regarding force
      amplitude and midpoint changes, but falsify predictions of an earlier proposed
      model with respect to the relative phase changes. We discuss factors that could
      contribute to the observed relative phase drift in the one-hand tasks including
      the leader-follower pattern generalized for two-effector tasks performed by one
      person.

PMID- 29335752
TI  - Diagnosis and management of long-bone nonunions: a nationwide survey.
AB  - PURPOSE: There is variability among surgeons on definitions regarding the degree
      of bone healing of long-bone fractures. A lack of consensus may negatively affect
      communication between surgeons, and lead to unintended and unwanted variability
      in treatment of patients suffering from abnormal healing of long-bone fractures.
      We aimed to identify differences between surgeons regarding their views on the
      degree of union of long-bone fractures. METHODS: We performed a survey among 114
      surgeons who worked at 11 level I trauma centers and 68 level II/III hospitals in
      the Netherlands. We asked them to represent their institutional colleagues and
      answer questions regarding their views on the definition, factors influencing
      bone healing, clinical practice, views on scientific evidence, and the use or
      need of guidelines for non-union of long-bone fractures. A total of 26 trauma
      surgeons and 37 orthopedic surgeons responded (59%). RESULTS: Compared to trauma
      surgeons, more orthopedic surgeons maintain 6 months as the timeframe for
      classifying a fracture without healing tendencies as a non-union fracture (50 vs
      70%; P = 0.019). Compared to orthopedic surgeons, trauma surgeons use the bone
      scan (46 vs 19%; P = 0.027) and the PET scan (50 vs 5.4%; P < 0.001) more often,
      and consider medication use to be a factor influencing bone healing more often
      (92 vs 69%; P = 0.040). Furthermore, they utilize bone marrow aspiration (35 vs
      11%; P = 0.029), reaming of long bones (96 vs 70%; P = 0.010), synthetic bone
      substitutes (31 vs 5.4%; P = 0.012), bone morphogenetic proteins (58 vs 16%; P =
      0.001), and the Diamond concept (92 vs 8.1%) more often as treatment modalities
      for non-union of long-bone fractures. Surgeons agreed on that intramedullary nail
      osteosynthesis was the treatment option supported by the highest level of
      evidence. 80% of the respondents feel a need for a clinical guideline on the
      management of long-bone non-union. CONCLUSION: There is no consensus among
      surgeons on the definition, factors influencing healing, clinical practice, and
      scientific evidence regarding non-union of long-bone fractures. The vast majority
      of surgeons believe that their practice would benefit from (inter)national
      guidelines on this topic, and efforts should be made to reduce surgeon-to-surgeon
      variability in treatment recommendations and facilitate more homogenous
      scientific research on non-union of long-bone fractures. LEVEL OF EVIDENCE: Level
      V.

PMID- 29335751
TI  - Transcranial direct current stimulation enhances foot sole somatosensation when
      standing in older adults.
AB  - Foot-sole somatosensation is critical for safe mobility in older adults.
      Somatosensation arises when afferent input activates a neural network that
      includes the primary somatosensory cortex. Transcranial direct current
      stimulation (tDCS), as a strategy to increase somatosensory cortical
      excitability, may, therefore, enhance foot-sole somatosensation. We hypothesized
      that a single session of tDCS would improve foot-sole somatosensation, and thus
      mobility, in older adults. Twenty healthy older adults completed this randomized,
      double-blinded, cross-over study consisting of two visits separated by one week.
      On each visit, standing vibratory threshold (SVT) of each foot and the timed-up
      and-go test (TUG) of mobility were assessed immediately before and after a 20-min
      session of tDCS (2.0 mA) or sham stimulation with the anode placed over C3
      (according to the 10/20 EEG placement system) and the cathode over the
      contralateral supraorbital margin. tDCS condition order was randomized. SVT was
      measured with a shoe insole system. This system automatically ramped up, or down,
      the amplitude of applied vibrations and the participant stated when they could or
      could no longer feel the vibration, such that lower SVT reflected better
      somatosensation. The SVTs of both foot soles were lower following tDCS as
      compared to sham and both pre-test conditions [F(1,76) > 3.4, p < 0.03]. A trend
      towards better TUG performance following tDCS was also observed [F(1,76) = 2.4, p
      = 0.07]. Greater improvement in SVT (averaged across feet) moderately correlated
      with greater improvement in TUG performance (r = 0.48, p = 0.03). These results
      suggest that tDCS may enhance lower-extremity somatosensory function, and
      potentially mobility, in healthy older adults.

PMID- 29335756
TI  - Lead-Induced Physiological, Biochemical and Enzymatic Changes in Asplenium
      scolopendrium L.
AB  - The paper aims to determine the lead-induced physiological, biochemical and
      enzymatic changes in Asplenium scolopendrium, which could represent biomarkers
      used in environmental assessment. Of all the physiological processes,
      photosynthesis and respiration were analyzed and the enzymatic and biochemical
      determinations focused on catalase activity, assimilatory pigment concentration,
      polyphenol content and lead presence in tissues.The stress induced by the
      exposure to Pb of the species Asplenium scolopendrium determined an increase in
      the carotenoid content, the catalase activity, the total polyphenol content and
      also enhanced the respiration potential. No significant changes were recorded
      regarding the chlorophyll content and the photosynthetic activity. The recorded
      changes may be used as non-specific markers in the assessment of the impact of Pb
      on plants (Asplenium scolopendrium).

PMID- 29335757
TI  - Total Mercury in Squalid Callista Megapitaria squalida from the SW Gulf of
      California, Mexico: Tissue Distribution and Human Health Risk.
AB  - We evaluated the total Hg concentration in different tissues of squalid callista
      Megapitaria squalida in order to measure Hg distribution in tissue and to
      estimate human health risk. Samples were obtained by free diving in the SW Gulf
      of California, Mexico. Concentrations are given on a wet weight basis. A total of
      89 squalid callista specimens were obtained, presenting an average Hg
      concentration of 0.07 +/- 0.04 ug g-1. There were no significant differences (p >
      0.05) in Hg concentration between tissues (visceral mass = 0.09 +/- 0.08 ug g-1;
      mantle = 0.06 +/- 0.07 ug g-1; muscle = 0.06 +/- 0.04 ug g-1). The low Hg values
      found in squalid callista and its low risk quotient (HQ = 0.03) suggest that the
      consumption of squalid callista does not represent a human health risk. However,
      HQ calculated using MeHg was > 1, it which could indicate a potential risk
      related to consumption of clams.

PMID- 29335749
TI  - Diversity among POU transcription factors in chromatin recognition and cell fate
      reprogramming.
AB  - The POU (Pit-Oct-Unc) protein family is an evolutionary ancient group of
      transcription factors (TFs) that bind specific DNA sequences to direct gene
      expression programs. The fundamental importance of POU TFs to orchestrate
      embryonic development and to direct cellular fate decisions is well established,
      but the molecular basis for this activity is insufficiently understood. POU TFs
      possess a bipartite 'two-in-one' DNA binding domain consisting of two
      independently folding structural units connected by a poorly conserved and
      flexible linker. Therefore, they represent a paradigmatic example to study the
      molecular basis for the functional versatility of TFs. Their modular architecture
      endows POU TFs with the capacity to accommodate alternative composite DNA
      sequences by adopting different quaternary structures. Moreover, associations
      with partner proteins crucially influence the selection of their DNA binding
      sites. The plentitude of DNA binding modes confers the ability to POU TFs to
      regulate distinct genes in the context of different cellular environments.
      Likewise, different binding modes of POU proteins to DNA could trigger
      alternative regulatory responses in the context of different genomic locations of
      the same cell. Prominent POU TFs such as Oct4, Brn2, Oct6 and Brn4 are not only
      essential regulators of development but have also been successfully employed to
      reprogram somatic cells to pluripotency and neural lineages. Here we review
      biochemical, structural, genomic and cellular reprogramming studies to examine
      how the ability of POU TFs to select regulatory DNA, alone or with partner
      factors, is tied to their capacity to epigenetically remodel chromatin and drive
      specific regulatory programs that give cells their identities.

PMID- 29335758
TI  - Toxicity of Diclofenac in the Fern Azolla filiculoides and the Lichen Xanthoria
      parietina.
AB  - This study investigated the occurrence of toxicity, expressed as damage to the
      photosynthetic apparatus, in the aquatic fern Azolla filiculoides and the lichen
      Xanthoria parietina following treatments with diclofenac at different
      concentrations (0.1, 1, 10 and 100 mg/L) and different exposure times (24, 48, 72
      and 240 h). Measurements of photosynthetic efficiency, chlorophyll content and
      chlorophyll degradation indicated dose- and time-dependent toxicity, since
      significant differences with control samples as well as among treatments, emerged
      mainly for the highest concentration (100 mg/L) and the longest time (240 h). In
      addition, also the mycobiont of the lichen X. parietina showed similar toxic
      effects, expressed as ergosterol content. The absence of relevant alterations at
      the lowest concentration (0.1 mg/L) suggested a very limited susceptibility of
      these species to environmentally relevant levels of this pharmaceutical.

PMID- 29335759
TI  - Bone-mediated anteroinferior glenohumeral instability : Current concepts.
AB  - Recurrent anterior shoulder instability is commonly associated with defects of
      the anterior glenoid rim. Substantial osseous defects significantly diminish the
      glenohumeral stability and require a bony augmentation, either by a coracoid
      transfer or free bone grafting procedure. Both reconstructive techniques have
      been applied for a long time and evaluated biomechanically and clinically.
      Although neither treatment option has been recognized as clearly superior, both
      comprise certain advantages and disadvantages. The Latarjet technique enables a
      biomechanically superior stabilization through the additional sling effect at
      time zero, but constitutes an extra-anatomical procedure with a broad spectrum
      and relatively high incidence of complications. Free bone grafting techniques
      enable an anatomical reconstruction of the glenoid concavity, offer the advantage
      of an unlimited graft size and show generally less severe and more easily
      manageable complications. The indications need to be carefully considered
      depending on the specific defect type, the glenoid track concept in cases of
      bipolar lesions as well as the individual patient characteristics. For both
      reconstructive procedures, open and arthroscopic approaches have been described
      with very good results, allowing a selection based on individual surgical skills
      and experience levels.

PMID- 29335760
TI  - [Current aspects and new techniques in dislocation of the shoulder joint].
AB  - With 12% of all injuries concerning the shoulder, acromioclavicular (AC) joint
      dislocations are a common injury especially in young and active patients. The
      Rockwood classification is widely accepted, which differentiates between six
      types depending on the degree of injury and the vertical dislocation. Because the
      classification does not adequately address the horizontal instability, its
      benefits are questionable and there is currently no consensus. For this reason,
      the classification and the therapy of these injuries are increasingly becoming
      the subject of scientific investigations. Whereas conservative treatment for type
      I and II injuries and operative treatment for type IV-VI injuries are widely
      accepted, there is still no agreement in treating type III lesions. The goal of
      this review article is to present the current evidence for the diagnostics,
      different classifications and therapeutic possibilities.

PMID- 29335761
TI  - Adjacent intervertebral space infection after lumbar fusion.
AB  - BACKGROUND: Surgical site infection is a catastrophic complication after spinal
      surgery, which seriously affects the progress of rehabilitation and clinical
      outcome. Currently the clinical reports on spinal surgical site infections are
      mostly confined to the surgical segment itself and there are few reports on
      adjacent segment infections after spinal surgery. STUDY DESIGN: Case report.
      OBJECTIVE: To report a clinical case with adjacent level infection after spinal
      fusion. METHODS: We report the case of a 68-year-old woman who underwent
      posterior lumbar 4-5 laminectomy, posterolateral fusion and internal fixation.
      The patient showed signs of surgical site infection, such as surgical site pain,
      high fever and increase of the inflammatory index 1 week after the operation.
      Magnetic resonance imaging (MRI) confirmed the diagnosis of adjacent
      intervertebral disc infection. The patient received early combined, high-dose
      anti-infection treatment instead of debridement. RESULTS: After the conservative
      treatment, the infection was controlled and the patient subsequently enjoyed a
      normal daily life. CONCLUSION: Adjacent level infections can occur after spinal
      surgery. Early diagnosis and anti-infection treatment played an important role in
      the treatment of this kind of complication.

PMID- 29335763
TI  - 18F-Fluorocholine PET/CT as a second line nuclear imaging technique before
      surgery for primary hyperparathyroidism.

PMID- 29335764
TI  - Pulmonary 18F-FDG uptake helps refine current risk stratification in idiopathic
      pulmonary fibrosis (IPF).
AB  - PURPOSE: There is a lack of prognostic biomarkers in idiopathic pulmonary
      fibrosis (IPF) patients. The objective of this study is to investigate the
      potential of 18F-FDG-PET/ CT to predict mortality in IPF. METHODS: A total of 113
      IPF patients (93 males, 20 females, mean age +/- SD: 70 +/- 9 years) were
      prospectively recruited for 18F-FDG-PET/CT. The overall maximum pulmonary uptake
      of 18F-FDG (SUVmax), the minimum pulmonary uptake or background lung activity
      (SUVmin), and target-to-background (SUVmax/ SUVmin) ratio (TBR) were quantified
      using routine region-of-interest analysis. Kaplan-Meier analysis was used to
      identify associations of PET measurements with mortality. We also compared PET
      associations with IPF mortality with the established GAP (gender age and
      physiology) scoring system. Cox analysis assessed the independence of the
      significant PET measurement(s) from GAP score. We investigated synergisms between
      pulmonary 18F-FDG-PET measurements and GAP score for risk stratification in IPF
      patients. RESULTS: During a mean follow-up of 29 months, there were 54 deaths.
      The mean TBR +/- SD was 5.6 +/- 2.7. Mortality was associated with high pulmonary
      TBR (p = 0.009), low forced vital capacity (FVC; p = 0.001), low transfer factor
      (TLCO; p < 0.001), high GAP index (p = 0.003), and high GAP stage (p = 0.003).
      Stepwise forward-Wald-Cox analysis revealed that the pulmonary TBR was
      independent of GAP classification (p = 0.010). The median survival in IPF
      patients with a TBR < 4.9 was 71 months, whilst in those with TBR > 4.9 was 24
      months. Combining PET data with GAP data ("PET modified GAP score") refined the
      ability to predict mortality. CONCLUSIONS: A high pulmonary TBR is independently
      associated with increased risk of mortality in IPF patients.

PMID- 29335765
TI  - Wastewater-based tracing of doping use by the general population and amateur
      athletes.
AB  - The present study investigates the applicability of the chemical analysis of
      wastewater to assess the use of doping substances by the general population and
      amateur athletes. To this end, an analytical methodology that can identify and
      quantify a list of 15 substances from the groups of anabolic steroids, weight
      loss products, and masking agents in wastewater has been developed. The method
      uses solid phase extraction to increase the detection sensitivity of the target
      analytes, expected to be present at very low concentrations (ng L-1 range), and
      decrease possible matrix interferences. Instrumental analysis is performed by
      liquid chromatography coupled to high-resolution mass spectrometry, allowing data
      acquisition in both full scan and tandem MS mode. The method has been
      successfully validated at two concentration levels (50 and 200 ng L-1) with
      limits of quantification ranging between 0.7 and 60 ng L-1, intra- and inter-day
      precision expressed as relative standard deviation below 15%, procedural
      recoveries between 60 and 160% and matrix effects ranging from 45 to 121%. The
      stability of the analytes in wastewater was evaluated at different storage
      temperatures illustrating the importance of freezing the samples immediately
      after collection. The application of the method to 24-h composite wastewater
      samples collected at the entrance of three wastewater treatment plants and one
      pumping station while different sport events were taking place revealed the
      presence in wastewater, and hence the use, of the weight loss substances
      ephedrine, norephedrine, methylhexanamine, and 2,4-dinitrophenol. The use of
      these stimulants was visible just prior and during the event days and in greater
      amounts than anabolic steroids or masking agents. Graphical abstract Chemical
      analysis of untreated wastewater reveals the use of prohibited doping substances
      during amateur sport event.

PMID- 29335766
TI  - Magnetofluorescent nanocomposites and quantum dots used for optimal application
      in magnetic fluorescence-linked immunoassay.
AB  - Magnetofluorescent nanocomposites with optimal magnetic and fluorescent
      properties were prepared and characterized by combining magnetic nanoparticles
      (iron oxide@polymethyl methacrylate) with fluorescent nanoparticles (rhodamine
      6G@mSiO2). Experimental parameters were optimized to produce nanocomposites with
      high magnetic susceptibility and fluorescence intensity. The detection of a model
      biomarker (alpha-fetoprotein) was used to demonstrate the feasibility of applying
      the magnetofluorescent nanocomposites combined with quantum dots and using
      magnetic fluorescence-linked immunoassay. The magnetofluorescent nanocomposites
      enable efficient mixing, fast re-concentration, and nanoparticle quantization for
      optimal reactions. Biofunctional quantum dots were used to confirm the alpha
      fetoprotein (AFP) content in sandwich immunoassay after mixing and washing. The
      analysis time was only one third that required in ELISA. The detection limit was
      0.2 pg mL-1, and the linear range was 0.68 pg mL-1-6.8 ng mL-1. This detection
      limit is lower, and the linear range is wider than those of ELISA and other
      methods. The measurements made using the proposed method differed by less than
      13% from those obtained using ELISA for four AFP concentrations (0.03, 0.15,
      0.75, and 3.75 ng mL-1). The proposed method has a considerable potential for
      biomarker detection in various analytical and biomedical applications. Graphical
      abstract Magnetofluorescent nanocomposites combined with fluorescent quantum dots
      were used in magnetic fluorescence-linked immunoassay.

PMID- 29335762
TI  - Targeting PSMA by radioligands in non-prostate disease-current status and future
      perspectives.
AB  - BACKGROUND: Prostate-specific membrane antigen (PSMA) is the up-and-coming target
      for molecular imaging of prostate cancer. Despite its name, non-prostate-related
      PSMA expression in physiologic tissue as well as in benign and malignant disease
      has been reported in various publications. Unlike in prostate cancer, PSMA
      expression is only rarely observed in non-prostate tumor cells. Instead,
      expression occurs in endothelial cells of tumor-associated neovasculature,
      although no endothelial expression is observed under physiologic conditions. The
      resulting potential for tumor staging in non-prostate malignant tumors has been
      demonstrated in first patient studies. This review summarizes the first clinical
      studies and deduces future perspectives in staging, molecular characterization,
      and PSMA-targeted radionuclide therapy based on histopathologic examinations of
      PSMA expression. CONCLUSIONS: The non-exclusivity of PSMA in prostate cancer
      opens a window to utilize the spectrum of available radioactive PSMA ligands for
      imaging and molecular characterization and maybe even therapy of non-prostate
      disease.

PMID- 29335767
TI  - Atrial fibrillation and MPNs.

PMID- 29335769
TI  - An adolescent presenting with acquired acute renal damage: Questions.

PMID- 29335770
TI  - An adolescent presenting with acquired acute renal damage: Answers.

PMID- 29335768
TI  - CTLA-4 polymorphisms: influence on transplant-related mortality and survival in
      children undergoing allogeneic hematopoietic stem cell transplantation.
AB  - PURPOSE: Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative
      approach for a variety of hematological diseases; however, it is still associated
      with substantial morbidity and mortality. Transplant-related mortality (TRM)
      after HSCT depends mainly on the toxicity of the conditioning regimen,
      infections, and graft-versus-host disease. The purpose of this study was to
      identify the association between CTLA-4 single nucleotide polymorphisms and TRM
      in children undergoing allogeneic HSCT. METHODS: 153 donors and 153 children with
      acute lymphoblastic leukemia, acute myeloid leukemia or juvenile myelomonocytic
      leukemia who had undergone allogeneic HSCT were genotyped of CTLA-4 gene for
      rs3087243 (CT60G>A), rs231775 (+ 49 A>G) and rs4553808 using TaqMan real-time
      polymerase chain reaction. RESULTS: We observed a significant association between
      the donor's CLTA-4 genotype of rs3087243 and TRM in children undergoing
      allogeneic HSCT. Genotype AG was found in 78 donors (51%), GG in 44 donors (29%)
      and 31 donors (20%) were homozygous for AA. 30 patients died as a result of
      transplant-related causes. Interestingly, we observed a significantly reduced TRM
      in children who were transplanted from a donor with the CTLA-4 genotype GG in
      comparison to genotype AG or AA (9 versus 19 versus 36%, P = 0.013). In addition,
      we found significant differences of event-free survival (EFS) depending on the
      donor's genotype. The EFS was 64, 46 or 32% if the patient was transplanted from
      a donor with CTLA-4 genotype GG, AG or AA, respectively (P = 0.043). In
      multivariate analysis, CTLA-4 genotype of rs3087243 was an independent risk
      factor for TRM (P = 0.011) and EFS (P = 0.035). CONCLUSION: This study provides
      first evidence that the CTLA-4 polymorphisms are significant risk factors for TRM
      and survival in children undergoing allogeneic HSCT and should be evaluated in
      further trials.

PMID- 29335772
TI  - Investigation on the correlation between energy deposition and clustered DNA
      damage induced by low-energy electrons.
AB  - This study presents the correlation between energy deposition and clustered DNA
      damage, based on a Monte Carlo simulation of the spectrum of direct DNA damage
      induced by low-energy electrons including the dissociative electron attachment.
      Clustered DNA damage is classified as simple and complex in terms of the
      combination of single-strand breaks (SSBs) or double-strand breaks (DSBs) and
      adjacent base damage (BD). The results show that the energy depositions
      associated with about 90% of total clustered DNA damage are below 150 eV. The
      simple clustered DNA damage, which is constituted of the combination of SSBs and
      adjacent BD, is dominant, accounting for 90% of all clustered DNA damage, and the
      spectra of the energy depositions correlating with them are similar for different
      primary energies. One type of simple clustered DNA damage is the combination of a
      SSB and 1-5 BD, which is denoted as SSB + BD. The average contribution of SSB +
      BD to total simple clustered DNA damage reaches up to about 84% for the
      considered primary energies. In all forms of SSB + BD, the SSB + BD including
      only one base damage is dominant (above 80%). In addition, for the considered
      primary energies, there is no obvious difference between the average energy
      depositions for a fixed complexity of SSB + BD determined by the number of base
      damage, but average energy depositions increase with the complexity of SSB + BD.
      In the complex clustered DNA damage constituted by the combination of DSBs and BD
      around them, a relatively simple type is a DSB combining adjacent BD, marked as
      DSB + BD, and it is of substantial contribution (on average up to about 82%). The
      spectrum of DSB + BD is given mainly by the DSB in combination with different
      numbers of base damage, from 1 to 5. For the considered primary energies, the DSB
      combined with only one base damage contributes about 83% of total DSB + BD, and
      the average energy deposition is about 106 eV. However, the energy deposition
      increases with the complexity of clustered DNA damage, and therefore, the
      clustered DNA damage with high complexity still needs to be considered in the
      study of radiation biological effects, in spite of their small contributions to
      all clustered DNA damage.

PMID- 29335771
TI  - Risk perception of heat waves and its spatial variation in Nanjing, China.
AB  - The intensity, frequency, and duration of heat waves are expected to increase
      with climate change. In this study, we found a significant difference of public
      perceived effects of heat waves and trust in government among urban, suburban,
      and rural districts. Rural residents had a significant higher effect perception
      than urbanites and also showed stronger willingness to have medical insurance or
      regular physical examinations. Meanwhile, suburban residents had the lowest trust
      perception in government among these three districts, which may be due to
      suburban districts' unique social structure and complex social issues. Besides,
      we assessed the relationship between the factor effect and demographic variables.
      The results showed that urban respondents' effect perception was significantly
      related to heat wave experiences. Suburban respondents' effect perception was
      significantly related to age, income, and heat wave experiences. And rural
      respondents' effect perception was significantly related to income and chronic
      diseases. Based on our results, much more attention needs to be paid to rural
      districts. The government should strengthen infrastructure construction such as
      cooling centers, improve emergency response plans and mechanisms, and increase
      reserves of emergency supplies in rural districts. Also, targeted risk
      communication is of the equal importance to aid the policy-makers improving the
      relationship with the public and regaining the public's trust and support.

PMID- 29335773
TI  - Effects of combining ergonomic interventions and motor control exercises on
      muscle activity and kinematics in people with work-related neck-shoulder pain.
AB  - PURPOSE: This study compared the effects of "Ergomotor" intervention and
      conventional physiotherapy, on influencing the motor control in the neck-shoulder
      region in people with work-related neck-shoulder pain (WRNSP). METHODS: 101
      patients (age range 20-54 years) diagnosed with chronic WRNSP were randomized
      into control (CO) group (n = 50) and Ergomotor (EM) group (n = 51). Each group
      received a 12-week intervention. Participants in CO group received treatment for
      pain relief and general exercises. EM group received individualized motor control
      training and advice of ergonomic modifications at their workplaces. RESULTS: At
      post-intervention, EM group showed significant reduction of bilateral upper
      trapezius muscle activity during active neck movements (left: 40-35%, right: 35
      27%) and functional tasks such as lifting a weight forward-backward (left: 31
      21%, right: 22-14%) and upward-downward (left: 26-23%, right: 20-13%). Cervical
      erector spinae also showed significant decrease in muscle activity during some
      phases of the functional tasks (left: 13-6%, right: 10-2%). In contrast, CO group
      did not show such changes in muscle activity at post-intervention. EM group also
      showed significant increase in movement velocity and acceleration during active
      neck movements in all directions (from 18 to 31%), while CO group only showed
      significant increase in movement velocity in some directions. Both groups
      reported significant but similar reduction in pain scores, at post-intervention
      and 1-year follow-up. CONCLUSIONS: The present results provided some evidence to
      support the positive and sustainable benefits of integrating motor control
      training into the workplace postures and motions.

PMID- 29335774
TI  - Genomic trade-offs: are autism and schizophrenia the steep price of the human
      brain?
AB  - Evolution often deals in genomic trade-offs: changes in the genome that are
      beneficial overall persist even though they also produce disease in a subset of
      individuals. Here, we explore the possibility that such trade-offs have occurred
      as part of the evolution of the human brain. Specifically, we provide support for
      the possibility that the same key genes that have been major contributors to the
      rapid evolutionary expansion of the human brain and its exceptional cognitive
      capacity also, in different combinations, are significant contributors to autism
      and schizophrenia. Furthermore, the model proposes that one of the primary genes
      behind this trade-off may not technically be "a gene" or "genes" but rather are
      the highly duplicated sequences that encode the Olduvai protein domain family
      (formerly called DUF1220). This is not an entirely new idea. Others have proposed
      that the same genes involved in schizophrenia were also critical to the rapid
      expansion of the human brain, a view that has been expressed as "the same 'genes'
      that drive us mad have made us human". What is new is that a "gene", or more
      precisely a protein domain family, has been found that may satisfy these
      requirements.

PMID- 29335775
TI  - A new genus, Planticonsortium (Mucoromycotina), and new combination (P. tenue),
      for the fine root endophyte, Glomus tenue (basionym Rhizophagus tenuis).
AB  - In 1977, the fine root endophyte, originally named Rhizophagus tenuis, was
      transferred into the genus Glomus as G. tenue, thus positioning the species with
      all other known arbuscular mycorrhizal fungi (Glomeromycota, Glomeromycotina).
      Recent molecular evidence, however, places it in a different subphylum,
      Mucoromycotina in the Mucoromycota. No suitable genus exists in the
      Mucoromycotina to accommodate G. tenue, so it is moved to Planticonsortium gen.
      nov. as P. tenue comb. nov.

PMID- 29335776
TI  - MIGS: therapeutic success of combined Xen Gel Stent implantation with cataract
      surgery.
AB  - PURPOSE: Glaucoma, a common disease in the elderly population, is frequently
      coexistent with cataract. While the combination of filtration surgery and
      cataract surgery is a challenging topic with limited success, minimal invasive
      glaucoma surgery (MIGS), such as Xen Gel Stents, seems to provide promising
      results. The aim of this study was to investigate the complete and qualified
      therapeutic success of Xen Gel Stent implantation with (XenPhaco) and without
      cataract surgery. METHODS: One hundred and eleven open-angle glaucoma eyes
      underwent implantation of Xen45 Gel Stent (AqueSys, Inc.) with or without
      cataract operation. Complete therapeutic success was defined as target
      intraocular pressure (IOP) < 18 mmHg at any time point within 6 months of follow
      up without local antiglaucomatous therapy or further surgical interventions.
      Qualified success was defined as target IOP <18 mmHg with additional 1-2 local
      antiglaucomatous eye drops. Failure included all cases with the necessity of at
      least three local antiglaucomatous eye drops or additional glaucoma surgery.
      RESULTS: Combined implantation of Xen Gel Stent with cataract surgery was
      performed in 30 eyes and stand-alone Xen Gel Stent implantation was performed in
      81 eyes. A complete therapeutic success was achieved in 46.9% of single Xen Gel
      Stent implantation, whereas 53.3% was reached with combined XenPhaco. Qualified
      success was seen in 2.5% in the eyes of the single Xen Gel Stent implantation
      group and in 3.3% of the combined surgery group. Therapeutic failure rate was
      49.4% in the stand-alone group vs 46.7% in the combined group. Data were not
      significantly different for group and subgroup analyses. CONCLUSIONS: Complete
      and qualified therapeutic success is similar for the combination of Xen Gel Stent
      implantation with and without cataract surgery in open-angle glaucoma patients.
      MIGS using Xen Gel Stent can be recommended in situations if glaucoma surgery is
      indicated besides coexisting cataract.

PMID- 29335778
TI  - Hippocampal area CA2: properties and contribution to hippocampal function.
AB  - This review focuses on area CA2 of the hippocampus, as recent results have
      revealed the unique properties and surprising role of this region in encoding
      social, temporal and contextual aspects of memory. Originally identified and
      described by Lorente de No, in 1934, this region of the hippocampus has unique
      intra-and extra-hippocampal connectivity, sending and receiving input to septal
      and hypothalamic regions. Recent in vivo studies have indicated that CA2
      pyramidal neurons encode spatial information during immobility and play an
      important role in the generation of sharp-wave ripples. Furthermore, CA2 neurons
      act to control overall excitability in the hippocampal network and have been
      found to be consistently altered in psychiatric diseases, indicating that normal
      function of this region is necessary for normal cognition. With its unique role,
      area CA2 has a unique molecular profile, interneuron density and composition.
      Furthermore, this region has an unusual manifestation of synaptic plasticity that
      does not occur post-synaptically at pyramidal neuron dendrities but through the
      local network of inhibitory neurons. While much progress has recently been made
      in understanding the large contribution of area CA2 to social memory formation,
      much still needs to be learned.

PMID- 29335777
TI  - Fully automatic CT-histogram-based fat estimation in dead bodies.
AB  - Post-mortem body cooling is the foundation of temperature-based death time
      estimations (TDE) in homicide cases. Forensic science generally provides two
      types of p.m. body cooling models, the phenomenological and the physical models.
      Since both of them have to implement important individual parameters like the
      quantity of abdominal fat explicitly or implicitly, a more exact quantification
      and localization of abdominal fat is a desideratum in TDE. Particularly for the
      physical models, a better knowledge of the abdominal fat distribution could lead
      to relevant improvements in TDEs. Modern imaging methods in medicine like
      computed tomography (CT) are opening up the possibility to register the quantity
      and spatial distribution of body fat in individual cases with unprecedented
      precision. Since a CT-scan of an individual's abdominal region can comprise 1000
      slices as an order of magnitude, it is evident that their evaluation for body fat
      quantification and localization needs fully automated algorithms. The paper at
      hand describes the development and validation of such an algorithm called "CT
      histogram-based fat estimation and quasi-segmentation" (CFES). The approach can
      be characterized as a weighted least squares method dealing with the gray value
      histogram of single CT-slices only. It does not require any anatomical a priori
      information nor does it perform time-consuming feature detection on the CT
      images. The processing result consists in numbers quantifying the amount of
      abdominal body fat and of muscle-, organ-, and connective tissue. As a by
      product, CFES generates a quasi-segmentation of the slices processed
      differentiating fat from muscle-, organ-, and connective tissue. The tool is
      validated on synthetic data and on CT-data of a special phantom. It was also
      applied on a CT-scan of a dead body, where it produced anatomically plausible
      results.

PMID- 29335779
TI  - Equine neutrophils and their role in ischemia reperfusion injury and lung
      inflammation.
AB  - Horses are susceptible to a multitude of inflammatory conditions that are
      characterized by a strong neutrophilic response. Here, we review basic equine
      neutrophil biology and explore the role of neutrophils in inflammatory conditions
      with emphasis on intestinal ischemia and reperfusion injury and lung
      inflammation. In addition, unique aspects of equine neutrophil biology have been
      highlighted. Neutrophils comprise the highest proportion of circulating white
      blood cells in equine blood. The concentration of circulating equine neutrophils
      is a primary indicator of systemic inflammation. Additionally, equine neutrophils
      exposed to various stimulants develop "toxic" changes characterized as
      cytoplasmic basophilia, presence of Dohle bodies, cytoplasmic vacuolation and
      toxic granulation. In contrast to human neutrophils, equine neutrophils fail to
      undergo chemotaxis in response to the peptide N-formyl-methionyl-leucyl
      phenylalanine and are dependent on the addition of arachidonic acid due to
      reduced activity of phospholipase A2 to synthesize leukotrienes as part of the
      arachidonic acid pathway. Understanding the biologic function of neutrophils in
      horses is integral to developing methods to modulate inflammation associated with
      ischemia reperfusion injury and lung disease.

PMID- 29335781
TI  - Peripartum events associated with severe neurologic morbidity and mortality among
      acidemic neonates.
AB  - PURPOSE: To identify peripartum events that may predict the development of short
      term neurologic morbidity and mortality among acidemic neonates. METHODS:
      Retrospective case-control study conducted at a single-teaching hospital on data
      from January 2010 to December 2015. The study cohort group included all acidemic
      neonates (cord artery pH <= 7.1) born at >= 34 weeks. Primary outcome was a
      composite including any of the following: neonatal encephalopathy, convulsions,
      intra-ventricular hemorrhage, or neonatal death. The study cohort was divided to
      the cases group, i.e., acidemic neonates who had any component of the primary
      outcome, and a control group, i.e., acidemic neonates who did not experience any
      component of the primary outcome. RESULTS: Of all 24,311 neonates born >= 34
      weeks during the study period, 568 (2.3%) had a cord artery pH <= 7.1 and
      composed the cohort study group. Twenty-one (3.7%) neonates composed the cases
      group. Multivariate logistic regression analysis revealed that cases were
      significantly more likely to have experienced placental abruption (OR 18.78; 95%
      CI 5.57-63.26), born <= 2500 g (OR 13.58; 95% CI 3.70-49.90), have meconium (OR
      3.80; 95% CI 1.20-11.98) and cord entanglement (OR 5.99; 95% CI 1.79-20.06). The
      probability for developing the composite outcome rose from 3.7% with isolated
      acidemia to 97% among neonates who had all these peripartum events combined with
      intrapartum fetal heart rate tracing category 2 or 3. CONCLUSION: Neonatal
      acidemia carries a favorable outcome in the vast majority of cases. In
      association with particular antenatal and intrapartum events, the short-term
      outcome may be unfavorable.

PMID- 29335780
TI  - A comparison of semi-automated volumetric vs linear measurement of small
      vestibular schwannomas.
AB  - OBJECTIVE: Accurate and precise measurement of vestibular schwannoma (VS) size is
      key to clinical management decisions. Linear measurements are used in routine
      clinical practice but are prone to measurement error. This study aims to compare
      a semi-automated volume segmentation tool against standard linear method for
      measuring small VS. This study also examines whether oblique tumour orientation
      can contribute to linear measurement error. STUDY DESIGN: Experimental comparison
      of observer agreement using two measurement techniques. SETTING: Tertiary skull
      base unit. PARTICIPANTS: Twenty-four patients with unilateral sporadic small (<
      15 mm maximum intracranial dimension) VS imaged with 1 mm-thickness T1-weighted
      Gadolinium enhanced MRI. MAIN OUTCOME MEASURES: (1) Intra and inter-observer
      intraclass correlation coefficients (ICC), repeatability coefficients (RC), and
      relative smallest detectable difference (%SDD). (2) Mean change in maximum linear
      dimension following reformatting to correct for oblique orientation of VS.
      RESULTS: Intra-observer ICC was higher for semi-automated volumetric when
      compared with linear measurements, 0.998 (95% CI 0.994-0.999) vs 0.936 (95% CI
      0.856-0.972), p < 0.0001. Inter-observer ICC was also higher for volumetric vs
      linear measurements, 0.989 (95% CI 0.975-0.995) vs 0.946 (95% CI 0.880-0.976), p
      = 0.0045. The intra-observer %SDD was similar for volumetric and linear
      measurements, 9.9% vs 11.8%. However, the inter-observer %SDD was greater for
      volumetric than linear measurements, 20.1% vs 10.6%. Following oblique
      reformatting to correct tumour angulation, the mean increase in size was 1.14 mm
      (p = 0.04). CONCLUSION: Semi-automated volumetric measurements are more
      repeatable than linear measurements when measuring small VS and should be
      considered for use in clinical practice. Oblique orientation of VS may contribute
      to linear measurement error.

PMID- 29335782
TI  - Association of endogenous circulating sex steroids and condition-specific quality
      of life domains in postmenopausal women with pelvic floor disorders.
AB  - OBJECTIVE: To examine the relationship between endogenous sex steroids and
      various condition-specific quality of life domains in postmenopausal women with
      pelvic floor disorders. We hypothesized that woman with lowest androgen and
      estradiol concentrations would report worse scores of quality of life domains.
      METHODS: Forty-six women with pelvic organ prolapse (POP) and 47 cases with
      stress urinary incontinence (SUI) answered the validated pelvic floor
      questionnaire and underwent serum sex steroid measurement. A multivariate
      logistic regression model was used to determine the association between
      subjective outcome parameters and serum hormonal levels after adjusting for
      confounders. RESULTS: Univariate analysis revealed a strong inverse correlation
      between serum estradiol level (E2) and prolapse domain score (correlation
      coefficient = 0.005) as well as a significant positive correlation between SHBG
      level and prolapse domain score (correlation coefficient = 0.019) in cases with
      POP. Furthermore, the sex domain score showed a significant negative correlation
      with the androstendion (correlation coefficient = 0.020), DHEAS (correlation
      coefficient = 0.046) and testosterone level (correlation coefficient = 0.032) in
      the POP group. In the multivariate model, high serum SHBG (CI: 0.007-0.046)
      remained independently associated with worse scores in the prolapse domain and
      low serum DHEAS (CI: - 0.989 to 1.320) persisted as a significant predictor for a
      worse score in the sex domain. Regarding SUI cases, no association was noted
      between serum hormonal levels and quality of life related pelvic floor domains
      (correlation coefficient > 0.05). CONCLUSION: Our results suggest that pelvic
      floor related quality of life might also be affected by endogenous sex steroids
      in POP, but not in SUI cases.

PMID- 29335783
TI  - Maternal and neonatal omentin-1 levels in gestational diabetes.
AB  - PURPOSE: To evaluate the effect of gestational diabetes on omentin-1 in maternal
      and cord plasma. As a potent mediator of insulin resistance, Omentin-1, an
      adipokine derived from human adipose and placental tissue, may be an important
      player in the pathophysiology of gestational diabetes. METHODS: This was a
      prospective case-control study. The study included 96 women with gestational
      diabetes and 96 pregnant women without. Omentin-1 was measured at the time of the
      oral glucose tolerance test, at 32 weeks in maternal plasma and right after
      delivery in umbilical cord blood by ELISA assay. RESULTS: Over a period of 2
      years, 200 patients were enrolled. Omentin-1 levels did not significantly differ
      between both groups throughout the pregnancy: omentin-1 levels were 157 +/- 83
      ng/ml in women with gestational diabetes and 158 +/- 93 ng/ml in women without
      gestational diabetes (p = 0.94) at time of the oral glucose tolerance test and
      118 +/- 77 ng/ml in women with diabetes and 150 +/- 89 ng/ml in women without (p
      = 0.12) at 32 weeks, respectively. Both groups showed a decrease in omentin-1
      levels throughout pregnancy, with a more pronounced decrease in diabetic women
      (13 +/- 53 versus 4 +/- 48 ng/ml; p = 0.5). Neonatal omentin-1 levels were
      significantly lower in offspring of diabetic mothers: 106 +/- 61 versus 134 +/-
      45 ng/ml (p = 0.03). CONCLUSIONS: There was no significant difference in omentin
      1 levels between healthy and diabetic mothers throughout the pregnancy. However,
      we found significantly lower omentin-1 levels in offspring of diabetic mothers.
      This may indicate a risk for the development of insulin resistance in later life.

PMID- 29335784
TI  - Clinical significance of miRNA-21, -103, -129, -150 in serous ovarian cancer.
AB  - PURPOSE: We aimed to compare expression levels of miRNA-21, -103, -129, -150 in
      primary tumour tissues and its omental metastases from patients operated for
      advanced ovarian serous cancer. Expression levels of selected miRNAs were
      correlated with clinicopathological features, including chemosensitivity and
      survival. METHODS: We performed total RNA extraction from archival formalin-fixed
      paraffin-embedded tissue samples of primary serous ovarian cancer and omental
      metastases. The study included 48 patients with advanced ovarian cancer. The
      reference group consisted of 48 normal ovarian tissue samples. We performed cDNA
      synthesis, real time polymerase chain reaction and assessed relative expression
      of selected miRNAs. RESULTS: Samples derived from serous ovarian cancer were
      characterized by higher expression levels of miRNA-150 in comparison to omental
      metastases (p = 0.045). Furthermore, we observed that shorter progression free
      survival was associated with lower levels of miRNA-150 in metastatic tissues. We
      did not find similar relationships for other miRNAs. CONCLUSIONS: MiRNA-150 may
      potentially serve as a prognostic factor in advanced ovarian cancer. However,
      further studies are required to clearly confirm such hypothesis.

PMID- 29335785
TI  - Heterologous expression of rice 9-cis-epoxycarotenoid dioxygenase 4 (OsNCED4) in
      Arabidopsis confers sugar oversensitivity and drought tolerance.
AB  - BACKGROUND: The 9-cis-epoxycarotenoid dioxygenases OsNCED4 was cloned from rice
      in conjunction with OsNCED 1-3 and 5, of which 3 has been shown to function in
      ABA biosynthesis and alteration of leaf morphology. In higher plants, NCEDs have
      been shown to be key enzymes controlling ABA biosynthesis and belong to a
      differentially expressed gene family. Aside from OsNCED3, it remains largely
      unknown if other OsNCED genes are involved in ABA biosynthesis in rice. Thus,
      transgenic Arabidopsis plants overexpressing OsNCED4 were generated in the
      129B08/nced3 mutant background to explore OsNCED4 function in ABA biosynthesis.
      RESULTS: Heterologous expression of OsNCED4 in Arabidopsis increased ABA levels
      and altered plant size and leaf shape, delayed seed germination, caused sugar
      oversensitivity in post-germination growth, and enhanced tolerance to drought.
      The native OsNCED3 and OsNCED4 promoters were expressed in an overlapping pattern
      in rice seeds and young seedlings, suggesting possible functional redundancy
      between OsNCED3 and OsNCED4. At the one-leaf stage, similar regulation of OsNCED3
      and OsNCED4 gene expression in roots or leaves in response to moderate salt
      stress (150 mM NaCl) was observed. CONCLUSION: Like OsNCED3, OsNCED4 is
      functionally active in ABA biosynthesis in rice. OsNCED3 and OsNCED4 might play
      redundant roles in controlling ABA biosynthesis in rice, as suggested by GUS
      staining assay, but this should be further analyzed through complementation of
      rice NCED knockout mutants.

PMID- 29335786
TI  - Anti-inflammatory and antiplatelet effects of non-vitamin K antagonist oral
      anticoagulants in acute phase of ischemic stroke patients.
AB  - BACKGROUND: Recently, non-vitamin K antagonist oral anticoagulants such as direct
      thrombin and direct factor Xa inhibitors have been prescribed for prevention of
      embolic stroke. While in Japan, argatroban, also a direct thrombin inhibitor, is
      available for the treatment of atherothrombotic stroke patients. This study aimed
      to explore whether there is any differences between direct thrombin and direct
      factor Xa inhibitors regarding the inhibiting effect against thrombogenesis in
      the clinical setting of acute ischemic stroke. METHODS: Acute ischemic stroke
      patients newly prescribed anti-thrombotic agents were consecutively screened, and
      44 patients with single medicine were enrolled (median 72.0 years-old). Blood
      samples were obtained at 1 and 2 weeks after the medication started. The extent
      of anticoagulation activity, inflammatory markers and platelet aggregation were
      assessed. Patients with antiplatelets were used as control. RESULTS: Prescribed
      antithrombotics were dabigatran (group D: n = 12), apixaban (group A: n = 14) and
      antiplatelet agents (group P: n = 18). Prevalence of stroke risks and
      anticoagulation activity were not different between groups D and A. The
      alteration of inflammatory markers in a week in the group A showed similar trend
      to those in the group P. The group D presented relatively lower amount of high
      sensitive C-reactive protein and higher amount of pentraxin-3 compared with
      groups A and P. While 88.9% of group P patients showed decreased platelet
      aggregation activity with adenosine diphosphate, 55.6% of group D and 40.0% of
      group A presented the inhibition of platelet aggregation activity. CONCLUSIONS:
      Even in acute ischemic stroke patients, both apixaban and dabigatran equally
      showed the anticoagulation activity. The reduction of inflammatory response might
      be prominent in apixaban, whereas the inhibition of platelet aggregation activity
      might be evident in dabigatran.

PMID- 29335787
TI  - Synthesis of Water-Soluble Antimony Sulfide Quantum Dots and Their Photoelectric
      Properties.
AB  - Antimony sulfide (Sb2S3) has been applied in photoelectric devices for a long
      time. However, there was lack of information about Sb2S3 quantum dots (QDs)
      because of the synthesis difficulties. To fill this vacancy, water-soluble Sb2S3
      QDs were prepared by hot injection using hexadecyltrimethylammonium bromide
      (CTAB) and sodium dodecyl sulfate (SDS) mixture as anionic-cationic surfactant,
      alkanol amide (DEA) as stabilizer, and ethylenediaminetetraacetic acid (EDTA) as
      dispersant. Photoelectric properties including absorbing and emission were
      characterized by UV-Vis-IR spectrophotometer and photoluminescence (PL)
      spectroscopic technique. An intensive PL emission at 880 nm was found, indicating
      Sb2S3 QDs have good prospects in near-infrared LED and near-infrared laser
      application. Sb2S3 QD thin films were prepared by self-assembly growth and then
      annealed in argon or selenium vapor. Their band gaps (E g s) were calculated
      according to transmittance spectra. The E g of Sb2S3 QD thin film has been found
      to be tunable from 1.82 to 1.09 eV via annealing or selenylation, demonstrating
      the good prospects in photovoltaic application.

PMID- 29335788
TI  - Over-expression of a grafting-responsive gene from hickory increases abiotic
      stress tolerance in Arabidopsis.
AB  - KEY MESSAGE: A grafting response gene CcPIP1;2 was cloned from hickory plant,
      further functional characterization of the gene for water transport activity and
      abiotic stress tolerances were carried out through heterologous expression in
      Xenopus and Arabidopsis. Plasma membrane intrinsic proteins (PIPs) are
      multifunctional channel proteins belonging to the membrane intrinsic protein
      (MIP) family. In this study, a grafting-responsive gene from hickory (CcPIP1;2)
      was cloned and functionally characterized. Application of non-selective water
      inhibitors (HgCl2 and phloretin) led to the death of grafted hickory plants at 30
      days after grafting (DAG). Furthermore, the transcript accumulation of the
      selected CcPIP1;2 gene was gradually decreased from 0 to 14 DAG in the grafted
      samples under inhibitor treatment conditions. Transient expression analysis of
      the GFP-CcPIP1;2 fusion protein showed that CcPIP1;2 was located at plasma
      membrane. Heterologous expression of CcPIP1;2 protein in the Xenopus oocyte
      system helped the access of water into the cells. Over-expression of CcPIP1;2 in
      Arabidopsis improved the percentage of seed germination when the seeds were grown
      in H2O2-, ABA-, and mannitol-containing media, but had no effect when grown in
      the salt containing media. CcPIP1;2 transgenic plants grew better under drought
      conditions. The expression of various ABA-related stress marker genes as well as
      cell wall expansin marker genes was significantly higher in CcPIP1;2 over
      expression Arabidopsis lines than in the wild type (WT).

PMID- 29335789
TI  - First record of Trypanosoma dionisii of the T. cruzi clade from the Eastern bent
      winged bat (Miniopterus fuliginosus) in the Far East.
AB  - Chiropteran mammals worldwide harbour trypanosomes (Euglenozoa: Kinetoplastea:
      Trypanosomatida) of the subgenus 'Schizotrypanum' in the classical sense.
      Latterly, these trypanosomes have been referred to as members of the 'Trypanosoma
      cruzi clade' as their phylogenetic relationships, structure and life cycle
      conform to T. cruzi, parasitising various terrestrial mammals as well as humans
      in Latin America. Little is known, however, about the trypanosome species in
      Asian bats. During a survey on Borrelia spp. in the Eastern bent-winged bat
      (Miniopterus fuliginosus) living in a cave in Wakayama Prefecture, Japan,
      incidental proliferation of trypanosomes was detected in two of 94 haemocultures.
      Squat or slender trypanosomes that proliferated in the cultures were 7.5-20.5 MUm
      in length between both body ends and 1.0-3.8 MUm in width with/without free
      flagella up to 14.5 MUm (n = 29). The nucleotide sequences of the small subunit
      ribosomal RNA gene (SSU rDNA; 2176 bp), large subunit ribosomal RNA gene (1365
      bp) and glycosomal glyceraldehyde-3-phosphate dehydrogenase gene (gGAPDH; 843 bp)
      of the present isolates were characterized to clarify their molecular
      phylogenetic position in T. cruzi-like trypanosomes. The newly obtained SSU rDNA
      and gGAPDH nucleotide sequences showed the highest identities with Brazilian and
      European isolates of Trypanosoma dionisii of the T. cruzi clade, ranging between
      99.4 and 99.7% or between 95.6 and 99.3% identities, respectively. Although
      multiple T. dionisii isolates from the North and South American continents showed
      the closest molecular genetic relatedness to the present Far East isolates, only
      short SSU rDNA segments of the former isolates were deposited. Therefore, a
      definitive conclusion cannot be made until full nucleotide sequencing of at least
      the American isolates' SSU rDNA is available. This is the first confirmation of a
      Far East distribution of T. dionisii, demonstrating a wide geographical
      distribution of the species in the Eurasian and American continents with a
      limited nucleotide variation.

PMID- 29335790
TI  - Echinococcus multilocularis (Cestoda, Cyclophyllidea, Taeniidae): origin,
      differentiation and functional ultrastructure of the oncospheral tegument and
      hook region membrane.
AB  - Both the oncospheral tegument and the hook region membrane (HRM) of Echinococcus
      multilocularis hexacanths originate from a syncytial binucleate complex that
      appears in the early stage of morphogenesis and organogenesis of the hexacanth
      larva. The primordium of this binucleate complex forms a binucleate syncytial cap
      or "calotte" situated beneath the inner envelope at one pole of the developing
      embryo. During oncospheral differentiation, the binucleate perikaryon of the
      syncytial cap is sunk progressively deeper into the central part of the embryo,
      but remains always connected with the distal cytoplasm by a tendrillar
      cytoplasmic connection or bridge. Following migration or sinking of the
      binucleate perikaryon, numerous cytoplasmic vesicles appear in the distal
      cytoplasm. These vesicles fuse progressively together and form a single large
      cavity or lacuna. The walls of this cavity are becoming at this point the walls
      of two delaminated layers: (1) the distal anucleated cytoplasmic layer is
      transformed into the oncospheral tegument and (2) the proximal thin cytoplasmic
      layer is transformed into the "hook region membrane". This delamination of the
      initially compact layer of distal cytoplasm into two layers seems to be closely
      associated with differentiation of oncospheral hooks, the elongating blades of
      which protrude progressively into a newly formed cavity. The pressure of hook
      blades on the hook region membrane appears to facilitate its further separation
      from the basal layer of distal cytoplasm which is transformed into the peripheral
      layer of oncospheral tegument. In the mature oncosphere, the surface of this
      peripheral layer forms a regular brush border of cytoplasmic processes or
      microvilli and represents the true body covering of the hexacanth. The very thin
      cytoplasmic connection between the peripheral layer of tegument and binucleate
      perikaryon appears only very seldom in the ultrathin sections as a narrow
      cytoplasmic strand and has a plasma membrane that is reinforced by a single row
      of cortical microtubules. The HRM covers only one pole of the oncosphere and is
      attached to the oncosphere surface. The HRM is clearly visible in the mature
      oncosphere and is draped over the hook blades, the sharp points of which are
      protected by moderately electron-dense caps. Comparison of the above morphology
      with that of TEM study of the tegument of adult cestodes shows a great similarity
      as well as homology in the body covering of both larval and adult cestodes.

PMID- 29335791
TI  - Behavior of C-reactive protein in association with surgery of facial fracture and
      the influence of dexamethasone.
AB  - PURPOSE: To clarify pre- and postoperative C-reactive protein (CRP) levels in
      patients with facial fractures and to investigate the influence of
      perioperatively administered dexamethasone on postoperative CRP levels. PATIENTS
      AND METHODS: Facial fracture patients were randomized to receive perioperatively
      a total dose of 30 mg of dexamethasone (Oradexon(r)), whereas patients in the
      control group received no glucocorticoid. The analysis included patients who had
      CRP measured pre- and postoperatively. RESULTS: A total of 73 adult patients with
      facial fractures were included in the final analysis. Mean CRP level was elevated
      preoperatively and the level increased further after surgery. However,
      postoperative CRP rise was significantly impeded by dexamethasone (p < 0.001),
      regardless of gender, age, treatment delay, site of fracture, surgical approach,
      and duration of surgery. CRP rise halved on the 1st postoperative day when
      dexamethasone was used. In addition, dexamethasone resulted in a CRP decrease on
      the 2nd postoperative day, whereas the CRP rise continued in the control group.
      CONCLUSIONS: CRP rise is a normal body response after facial fracture and surgery
      that can be markedly reduced with dexamethasone. CRP changes should be considered
      with caution if perioperative dexamethasone is used.

PMID- 29335792
TI  - Toward Exploring the Structure of Monolayer to Few-layer TaS2 by Efficient
      Ultrasound-free Exfoliation.
AB  - Tantalum disulfide nanosheets have attracted great interest due to its electronic
      properties and device applications. Traditional solution-ased ultrasonic process
      is limited by ultrasound which may cause the disintegration into submicron-sized
      flake. Here, an efficient multi-step intercalation and ultrasound-free process
      has been successfully used to exfoliate 1T-TaS2. The obtained TaS2 nanosheets
      reveal an average thickness of 3 nm and several micrometers in size. The
      formation of few-layer TaS2 nanosheets as well as monolayer TaS2 sheets is
      further confirmed by atomic force microscopy images. The few-layer TaS2
      nanosheets remain the 1T structure, whereas monolayer TaS2 sheets show lattice
      distortion and may adopt the 1H-like structure with trigonal prism coordination.

PMID- 29335793
TI  - Accuracy of emergency department triage using the Emergency Severity Index and
      independent predictors of under-triage and over-triage in Brazil: a retrospective
      cohort analysis.
AB  - BACKGROUND: Emergency department (ED) triage is performed to prioritize care for
      patients with critical and time-sensitive illness. Triage errors create
      opportunity for increased morbidity and mortality. Here, we sought to measure the
      frequency of under- and over-triage of patients by nurses using the Emergency
      Severity Index (ESI) in Brazil and to identify factors independently associated
      with each. METHODS: This was a single-center retrospective cohort study. The
      accuracy of initial ESI score assignment was determined by comparison with a
      score entered at the close of each ED encounter by treating physicians with full
      knowledge of actual resource utilization, disposition, and acute outcomes. Chi
      square analysis was used to validate this surrogate gold standard, via comparison
      of associations with disposition and clinical outcomes. Independent predictors of
      under- and over-triage were identified by multivariate logistic regression.
      RESULTS: Initial ESI-determined triage score was classified as inaccurate for
      16,426 of 96,071 patient encounters. Under-triage was associated with a
      significantly higher rate of admission and critical outcome, while over-triage
      was associated with a lower rate of both. A number of factors identifiable at
      time of presentation including advanced age, bradycardia, tachycardia, hypoxia,
      hyperthermia, and several specific chief complaints (i.e., neurologic complaints,
      chest pain, shortness of breath) were identified as independent predictors of
      under-triage, while other chief complaints (i.e., hypertension and allergic
      complaints) were independent predictors of over-triage. CONCLUSIONS: Despite
      rigorous and ongoing training of ESI users, a large number of patients in this
      cohort were under- or over-triaged. Advanced age, vital sign derangements, and
      specific chief complaints-all subject to limited guidance by the ESI algorithm
      were particularly under-appreciated.

PMID- 29335795
TI  - Combined effects of predator cues and competition define habitat choice and food
      consumption of amphipod mesograzers.
AB  - Predation has direct impact on prey populations by reducing prey abundance. In
      addition, predator presence alone can also have non-consumptive effects on prey
      species, potentially influencing their interspecific interactions and thus the
      structure of entire assemblages. The performance of potential prey species may,
      therefore, depend on both the presence of predators and competitors. We studied
      habitat use and food consumption of a marine mesograzer, the amphipod
      Echinogammarus marinus, in the presence/absence of a fish mesopredator and/or an
      amphipod competitor. The presence of the predator affected both habitat choice
      and food consumption of the grazer, indicating a trade-off between the use of
      predator-free space and food acquisition. Without the predator, E. marinus were
      distributed equally over different microhabitats, whereas in the presence of the
      predator, most individuals chose a sheltered microhabitat and reduced their food
      consumption. Furthermore, habitat choice of the amphipods changed in the presence
      of interspecific competitors, also resulting in reduced feeding rates. The
      performance of E. marinus is apparently driven by trait-mediated direct and
      indirect effects caused by the interplay of predator avoidance and competition.
      This highlights the importance of potential non-consumptive impacts of predators
      on their prey organisms. The flexible responses of small invertebrate consumers
      to the combined effects of predation and competition potentially lead to changes
      in the structure of coastal ecosystems and the multiple species interactions
      therein.

PMID- 29335794
TI  - Effect of a calcitonin gene-related peptide-binding L-RNA aptamer on neuronal
      activity in the rat spinal trigeminal nucleus.
AB  - BACKGROUND: Calcitonin gene-related peptide (CGRP) plays a major role in the
      pathogenesis of migraine and other primary headaches. Spinal trigeminal neurons
      integrate nociceptive afferent input from trigeminal tissues including
      intracranial afferents, and their activity is thought to reflect facial pain and
      headache in man. CGRP receptor inhibitors and anti-CGRP antibodies have been
      demonstrated to be therapeutically effective in migraine. In parallel, CGRP
      receptor inhibition has been shown to lower spinal trigeminal neuron activity in
      animal models of meningeal nociception. METHODS: In a rat model of meningeal
      nociception, single cell activity of neurons in the spinal trigeminal nucleus
      with meningeal afferent input was recorded to test a further pharmacological
      approach, scavenging CGRP with a CGRP-binding L-RNA oligonucleotide, the L
      aptamer NOX-C89. Cumulative ascending doses of NOX-C89 were intravenously
      infused. RESULTS: Spontaneous activity of spinal trigeminal neurons did not
      change after 0.05 mg/kg NOX-C89, however, after additional infusion of 0.5 mg/kg
      and 5 mg/kg NOX-C89, spontaneous activity was dose-dependently reduced. Identical
      doses of a control L-aptamer had no effect. This pharmacological effect of NOX
      C89 was observed 10-25 min after infusion, but no difference was detected in the
      period 0-5 min. For comparison, the previously investigated CGRP receptor
      antagonist olcegepant had reduced activity within 5 min after infusion. Alongside
      the reduced spontaneous activity, after infusion of NOX-C89 the heat-induced
      neuronal activity was abolished. CONCLUSIONS: Scavenging CGRP by mirror-image RNA
      aptamers provides further evidence that this approach can be used to control
      spinal trigeminal activity.

PMID- 29335796
TI  - Association between frailty and bone loss in patients undergoing maintenance
      hemodialysis.
AB  - Frailty is significantly associated with bone loss in the general population.
      However, it is unclear whether this association also exists in patients
      undergoing hemodialysis who have chronic kidney disease-mineral and bone disorder
      (CKD-MBD). This study aimed to assess the association between frailty and bone
      loss in patients undergoing hemodialysis. This cross-sectional study included 214
      (90 women, 124 men) Japanese outpatients undergoing maintenance hemodialysis
      three times per week, with a mean age of 67.1 years (women) and 66.8 years (men).
      Frailty was defined based on criteria set forth by the Cardiovascular Health
      Study (CHS)-19 (21.1%) women and 47 (37.9%) men were robust, 41 (45.6%) women and
      43 (34.7%) men were pre-frail, and 30 (33.3%) women and 34 (27.4%) men were
      frail. For bone mass, quantitative ultrasound (QUS) parameters (speed of sound,
      broadband ultrasound attenuation, stiffness index) of the calcaneus were
      measured. The association between frailty and QUS parameters was determined
      separately for women and men using multivariate analysis of covariance (ANCOVA),
      with adjustments for clinical characteristics including age, body mass index,
      hemodialysis vintage, diabetes, current smoking, serum albumin, phosphate,
      corrected calcium, intact parathyroid hormone, and medication for CKD-MBD
      (vitamin D receptor activator, calcimimetics). ANCOVA revealed that all QUS
      parameters declined significantly with increasing levels of frailty in both sexes
      (P < 0.05). In conclusion, frailty (as defined by CHS criteria) should be
      considered a risk factor for bone loss in patients undergoing hemodialysis.

PMID- 29335798
TI  - 3D morphological change of skull base and fronto-temporal soft-tissue in the
      patients with unicoronal craniosynostosis after fronto-orbital advancement.
AB  - PURPOSE: This study aims to comprehensively evaluate the deformation of the skull
      base and fronto-temporal soft tissue in the patients with anterior plagiocephaly
      over 1 year of age by three-dimensional (3D) imaging after fronto-orbital
      advancement (FOA). METHODS: We quantitatively analyzed the surgical results and
      outcome of FOA performed in 10 patients with anterior plagiocephaly. The
      measurements of the skull base and fronto-temporal soft tissue were performed
      based on 3D computed tomography (CT) scan. We assessed symmetry of the skull base
      and fronto-temporal soft tissue change. RESULTS: The mean age of patients at FOA
      was 38.9 months. A significant asymmetry of the skull base was found in all the
      patients. The growth of the anterior and middle fossae was restricted and the
      deformation of the fronto-temporal region was marked by soft tissue measurements
      in different grades. On the follow-up CT images 23.6 months after surgery, there
      was prominent change (p < 0.05) between the two hemibases (CSO^ ratio) and
      between the lengths and angles of the anterior and middle cranial hemi-fossae
      (CX, CSX^, XSM^, XM ratio), especially in grade IIA. Anterior cranial vault
      asymmetry index obviously decreased to - 1.2 from 12% after surgery (p < 0.05).
      What's more, ACA^ was also proved to be less after surgical correction (19.91
      degrees  versus 8.29 degrees , p < 0.01) in grade IIA. The change of fronto
      temporal soft tissue was significant such as the frontal angle, the angle of the
      frontal plane, the fontal-temporal angle, and the angle of the temporal plane in
      different grades. CONCLUSIONS: The asymmetry of the skull base and the
      deformation of the fronto-temporal region can be presented by intracranial view
      at over 1 year of age in different grades. FOA can correct the skeletal
      malformation of the fronto-temporal region as well as soft tissue and the
      asymmetry of the skull base was improved after surgical treatment.

PMID- 29335799
TI  - Precisely Defined Polymers for Efficient Gene Delivery.
AB  - Gene therapy requires successful delivery of therapeutic nucleic acids into
      target cells; thus, efficient and safe gene delivery carriers are crucial to its
      success. Although many polymeric materials have shown their potential as
      effective nucleic acid carriers, the inherent heterogeneity and polydispersity of
      these polymers hinder their application in clinical studies because of
      difficulties in their further precise modification, structure-activity
      relationship study, as well as consistent manufacturing. Therefore, precisely
      defined polymers, with potential for site-specific optimization according to
      structure-activity relationship information and highly controllable production,
      have been extensively investigated. In this review, we focus on the design and
      development of precisely defined polymers for efficient gene delivery,
      illustrated with examples including dendrimers, peptide-based polymers, and
      sequence-defined oligoaminoamide oligomers.

PMID- 29335797
TI  - High-intensity aerobic interval training can lead to improvement in skeletal
      muscle power among in-hospital patients with advanced heart failure.
AB  - This study investigated the effectiveness and safety of interval training during
      in-hospital treatment of patients with advanced heart failure. Twenty-four
      consecutive patients with advanced symptomatic heart failure who were referred
      for cardiac transplant evaluation were recruited. After performing aerobic
      exercise for approximate intensity, high-intensity interval training (HIIT) was
      performed. The protocol consisted of 3 or 4 sessions of 1-min high-intensity
      exercise aimed at 80% of peak VO2 or 80% heart rate reserve, followed by 4-min
      recovery periods of low intensity. In addition to the necessary laboratory data,
      hand grip strength and knee extensor strength were evaluated at the start of
      exercise training and both at the start and the end of HIIT. Knee extensor
      strength was standardized by body weight. The BNP level at the start of exercise
      training was 432 (812) pg/mL and it significantly decreased to 254 (400) pg/mL (p
      < 0.001) at the end of HIIT. Hand grip strength did not change during course. By
      contrast, knee extensor strength significantly increased during HIIT [4.42 +/-
      1.43 -> 5.28 +/- 1.45 N/kg, p < 0.001], whereas the improvement of knee extensor
      strength was not significant from the start of exercise training to the start of
      HIIT. In addition, the change in knee extensor strength during HIIT was
      significantly associated with the hemoglobin A1c level at the start of exercise
      (R = - 0.55; p = 0.015). HIIT has a positive impact on skeletal muscle strength
      among in-hospital patients with advanced heart failure.

PMID- 29335800
TI  - Enrichment and characterization of a bacterial mixture capable of utilizing C
      mannosyl tryptophan as a carbon source.
AB  - C-Mannosylation, a protein-modification found in various eukaryotes, involves the
      attachment of a single mannose molecule to selected tryptophan residues of
      proteins. Since C-mannosyl tryptophan (CMW) was detected in human urine, it is
      generally thought that CMW is not catabolized inside our body and instead is
      excreted via the urine. This paper reports enrichment of a bacterial consortium
      from soil that degrades CMW. The bacteria grew in minimal medium supplemented
      with CMW as the carbon source. Interestingly, even after successive clonal picks
      of individual colonies, several species were still present in each colony as
      revealed by 16S rRNA gene sequence analysis, indicating that a single species may
      not be responsible for this activity. A next generation sequencing (NGS) analysis
      was therefore carried out in order to determine which bacteria were responsible
      for the catabolism of CMW. It was found that a species of Sphingomonadaceae
      family, but not others, increased with simultaneous decrease of CMW in the media,
      suggesting that this species is most likely the one that is actively involved in
      the degradation of CMW.

PMID- 29335801
TI  - IgM Augments Complement Bactericidal Activity with Serum from a Patient with a
      Novel CD79a Mutation.
AB  - Antibody replacement therapy for patients with antibody deficiencies contains
      only IgG. As a result, concurrent IgM and IgA deficiency present in a large
      proportion of antibody deficient patients persists. Especially patients with IgM
      deficiency remain at risk for recurrent infections of the gastrointestinal and
      respiratory tract. The lack of IgM in the current IgG replacement therapy is
      likely to contribute to the persistence of these mucosal infections because this
      antibody class is especially important for complement activation on the mucosal
      surface. We evaluated whether supplementation with IgM increased serum
      bactericidal capacity in vitro. Serum was collected from a patient with
      agammaglobulinemia and supplemented with purified serum IgM to normal levels.
      Antibody and complement deposition on the bacterial surface was determined by
      multi-color flow cytometry. Bacterial survival in serum was determined by colony
      forming unit counts. We present a patient previously diagnosed with
      agammaglobulinemia due to CD79A (Igalpha) deficiency revealing a novel pathogenic
      insertion variant in the CD79a gene (NM_001783.3:c.353_354insT). Despite IgG
      replacement therapy and antibiotic prophylaxis, this patient developed a
      Campylobacter jejuni spondylodiscitis of lumbar vertebrae L4-L5. We found that
      serum IgM significantly contributes to complement activation on the bacterial
      surface of C. jejuni. Furthermore, supplementation of serum IgM augmented serum
      bactericidal activity significantly. In conclusion, supplementation of
      intravenous IgG replacement therapy with IgM may potentially offer greater
      protection against bacterial infections, also in the context of increasing
      antibiotic resistance.

PMID- 29335802
TI  - The clinical relevance of drug-drug interaction between co-trimoxazole and
      sacubitril/valsartan treatment in a heart failure patient: a case report and
      overview of mechanisms and management in clinical practice.

PMID- 29335803
TI  - Contribution of transposable elements and distal enhancers to evolution of human
      specific features of interphase chromatin architecture in embryonic stem cells.
AB  - Transposable elements have made major evolutionary impacts on creation of primate
      specific and human-specific genomic regulatory loci and species-specific genomic
      regulatory networks (GRNs). Molecular and genetic definitions of human-specific
      changes to GRNs contributing to development of unique to human phenotypes remain
      a highly significant challenge. Genome-wide proximity placement analysis of
      diverse families of human-specific genomic regulatory loci (HSGRL) identified
      topologically associating domains (TADs) that are significantly enriched for
      HSGRL and designated rapidly evolving in human TADs. Here, the analysis of HSGRL,
      hESC-enriched enhancers, super-enhancers (SEs), and specific sub-TAD structures
      termed super-enhancer domains (SEDs) has been performed. In the hESC genome, 331
      of 504 (66%) of SED-harboring TADs contain HSGRL and 68% of SEDs co-localize with
      HSGRL, suggesting that emergence of HSGRL may have rewired SED-associated GRNs
      within specific TADs by inserting novel and/or erasing existing non-coding
      regulatory sequences. Consequently, markedly distinct features of the principal
      regulatory structures of interphase chromatin evolved in the hESC genome compared
      to mouse: the SED quantity is 3-fold higher and the median SED size is
      significantly larger. Concomitantly, the overall TAD quantity is increased by 42%
      while the median TAD size is significantly decreased (p = 9.11E-37) in the hESC
      genome. Present analyses illustrate a putative global role for transposable
      elements and HSGRL in shaping the human-specific features of the interphase
      chromatin organization and functions, which are facilitated by accelerated
      creation of novel transcription factor binding sites and new enhancers driven by
      targeted placement of HSGRL at defined genomic coordinates. A trend toward the
      convergence of TAD and SED architectures of interphase chromatin in the hESC
      genome may reflect changes of 3D-folding patterns of linear chromatin fibers
      designed to enhance both regulatory complexity and functional precision of GRNs
      by creating predominantly a single gene (or a set of functionally linked genes)
      per regulatory domain structures. Collectively, present analyses reveal critical
      evolutionary contributions of transposable elements and distal enhancers to
      creation of thousands primate- and human-specific elements of a chromatin folding
      code, which defines the 3D context of interphase chromatin both restricting and
      facilitating biological functions of GRNs.

PMID- 29335804
TI  - Identification of a functional toxin-antitoxin system located in the genomic
      island PYG1 of piezophilic hyperthermophilic archaeon Pyrococcus yayanosii.
AB  - Toxin-antitoxin (TA) system is bacterial or archaeal genetic module consisting of
      toxin and antitoxin gene that be organized as a bicistronic operon. TA system
      could elicit programmed cell death, which is supposed to play important roles for
      the survival of prokaryotic population under various physiological stress
      conditions. The phage abortive infection system (AbiE family) belongs to
      bacterial type IV TA system. However, no archaeal AbiE family TA system has been
      reported so far. In this study, a putative AbiE TA system (PygAT), which is
      located in a genomic island PYG1 in the chromosome of Pyrococcus yayanosii CH1,
      was identified and characterized. In Escherichia coli, overexpression of the
      toxin gene pygT inhibited its growth while the toxic effect can be suppressed by
      introducing the antitoxin gene pygA in the same cell. PygAT also enhances the
      stability of shuttle plasmids with archaeal plasmid replication protein Rep75 in
      E. coli. In P. yayanosii, disruption of antitoxin gene pygA cause a significantly
      growth delayed under high hydrostatic pressure (HHP). The antitoxin protein PygA
      can specifically bind to the PygAT promoter region and regulate the transcription
      of pygT gene in vivo. These results show that PygAT is a functional TA system in
      P. yayanosii, and also may play a role in the adaptation to HHP environment.

PMID- 29335805
TI  - Effects of nicotine on the biosynthesis of carotenoids in halophilic Archaea
      (class Halobacteria): an HPLC and Raman spectroscopy study.
AB  - Nicotine has a profound influence on the carotenoid metabolism in halophilic
      Archaea of the class Halobacteria. In a study of Halobacterium salinarum,
      Haloarcula marismortui and Halorubrum sodomense, using different analytical
      techniques to monitor the production of different carotenoids as a function of
      the presence of nicotine, we showed that the formation of alpha-bacterioruberin
      was inhibited in all. In Hbt. salinarum, addition of nicotine led to a
      significant change in the color of the culture due to the accumulation of
      lycopene, in addition to the formation of bisanhydrobacterioruberin which does
      not differ in color from alpha-bacterioruberin. Very little or no lycopene was
      formed in Har. marismortui and in Hrr. sodomense; instead
      bisanhydrobacterioruberin was the only major carotenoid found in nicotine-amended
      cultures. The findings are discussed in the framework of the recently elucidated
      biochemical pathway for the formation of the different carotenoid pigments
      encountered in the Halobacteria.

PMID- 29335806
TI  - Assessment of ocular toxoplasmosis patients reported at a tertiary center in the
      northeast of Iran.
AB  - PURPOSE: Ocular toxoplasmosis, which is caused by the single-cell parasite
      Toxoplasma gondii, is currently the most significant cause of posterior uveitis
      in the world. No previous studies have described the prevalence and clinical
      features of ocular toxoplasmosis in the northeast of Iran. The purpose of the
      current study was to address this gap. METHODS: In this retrospective study, the
      medical records of 488 uveitis patients who presented to the Khatam-al-Anbia Eye
      Hospital of Mashhad University of Medical Sciences, a tertiary ophthalmology
      center in the northeast of Iran, between January 2013 and December 2015 were
      evaluated. The clinical features and risk factors of 99 (20%) consecutive
      patients with ocular toxoplasmosis were extracted. RESULTS: Ninety-nine including
      53 (53.5%) female and 46 (46.5%) male patients with ocular toxoplasmosis were
      included in the analysis. Reduced vision (77%) and floaters (15.2%) were the most
      common presenting symptoms. The age category that was most affected by ocular
      toxoplasmosis was 20-40 years (range: 11-65 years) with a mean age of 27.2. All
      patients had retinochoroiditis, but just two had anterior uveitis. All of the
      extracted patients, with the exception of three patients, had unilateral
      involvement. None of the patients had any other medical disorders with the
      exception of one woman, who had diabetes. Only four recurring ocular
      toxoplasmosis patients were referred to the education hospital during the study.
      Serology data were available for just 32 patients, of which 31 (96.8%) were IgG
      positive, and 1 (3.2%) was IgM positive. CONCLUSION: Toxoplasma gondii was
      responsible for 20% of the patients of uveitis that presented to the largest
      ophthalmology center in the northeast of Iran. There is a high incidence of
      patients of ocular toxoplasmosis in the northeast of Iran, and it is a
      significant cause of uveitis and visual impairment in this area.

PMID- 29335807
TI  - Assessment of in vitro cytotoxic and genotoxic activities of some trimethoprim
      conjugates.
AB  - Trimethoprim, a commonly used antibacterial agent, is widely applied in the
      treatment of variety of infections in human. A few studies have demonstrated an
      extensive exposure of man to antibiotics, but there is still a lack of data for
      cytotoxic effects including nephrotoxicity, gastrointestinal toxicity,
      hematotoxicity, neurotoxicity and ototoxicity. The main purpose behind this study
      was to determine cytotoxic and genotoxic activities of trimethoprim (1),
      trimethoprim with maleic acid (2) and trimethoprim in conjugation with oxalic
      acid dihydrate (3). The cytotoxic effects of these three conjugates were
      elucidated by employing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoium
      bromide (MTT) assay using embryonic rat fibroblast-like cell line (F2408) and H
      ras oncogene activated embryonic rat fibroblast-like cancer cell line (5RP7).
      Additionally, determination of genotoxic activity of these three compounds were
      studied by using cytokinesis blocked micronucleus assay (CBMN) in human
      lymphocytes. The results demonstrated that trimethoprim alone and its combination
      with other compounds are able to induce both cytotoxic and genotoxic damage on
      cultured cells (F2408, 5RP7, human lymphocytes).

PMID- 29335808
TI  - Perfluorooctanoic acid impaired glucose homeostasis through affecting adipose AKT
      pathway.
AB  - Perfluorooctanoic acid (PFOA) is commonly applied in manufactured products, and
      its potential health risk is concerned greatly. Increasing evidences have
      indicated PFOA-induced liver dysfunction. However, detailed molecular mechanism
      has not been completely identified. In this study, we aimed to investigate the
      mechanical association between PFOA exposure and AKT pathway in white adipose
      tissue. As results, PFOA-treated mice showed increased blood glucose and insulin
      levels, and induced insulin resistance. In addition, serum levels of leptin and
      adiponectin in PFOA-treated mice were elevated. As shown in histological
      examination, increased cell death counts in PFOA-treated adipose were observed,
      as well as ultrastructural impairment in adipose cells was found. Further,
      immunohistochemical stains exhibited GLUT4, p-AKT positive cells were down
      regulated in PFOA-treated adipose, while PTEN immune-labeled cells were reduced.
      In validated data, RT-PCR assay suggested adipose AKT mRNA was down-regulated in
      PFOA-treated mice, and PTEN mRNA was increased. Western blot data showed that
      intracellular PTEN protein level in PFOA-treated adipose was up-regulated, while
      phosphorylation of AKT, GSK3beta levels were lowered dose-dependently. Taken
      together, the present findings indicate that PFOA impaired glucose homeostasis
      via negatively regulating AKT pathway in white adipose tissue.

PMID- 29335809
TI  - Healthcare and Social Services Providers Who Serve Sexual and Gender Minorities
      in a U.S.-Mexico Border City.
AB  - Sexual and gender minorities, including lesbian, gay, bisexual, transgender, and
      queer (LGBTQ) individuals, experience barriers to healthcare as a result of
      stigma, discrimination, and poor cultural competence by healthcare and social
      services providers (HCSSP). The purpose of the study is to increase access to
      care and services for the LGBTQ community in a U.S.-Mexico border city by
      identifying LGBTQ-friendly HCSSP. A survey, developed based on concerns voiced in
      a predominantly Hispanic LGBTQ community, was administered to HCSSP and used to
      create a referral list, "The Purple Pages of El Paso" (PPoEP). Overall, 77 HCSSP
      have responded and 43 are included in the most recent version of the PPoEP. This
      model for developing a referral list of providers can be adapted in areas where
      LGBTQ communities face similar barriers to care and services. To be effective in
      reducing barriers to care, PPoEP must be updatable and sustainable.

PMID- 29335810
TI  - Sexual and Reproductive Health Education Needs, Gender Roles Attitudes and
      Acceptance of Couple Violence According to Engaged Men and Women.
AB  - This descriptive study was aimed to evaluate the attitudes of the engaged men and
      women who are of legal age to marry towards gender roles and acceptance of couple
      violence, and determine their sexual/reproductive health education needs. It was
      conducted in two marriage registry offices in Ankara, Turkey. The study sample
      consisted of 740 participants. Data were collected by using semi-structured form,
      Gender Roles Attitude Scale and Acceptance of Couple Violence Scale. It was found
      that the engaged couples had educational needs concerning sexual/reproductive
      health; socio-demographic characteristics such as gender, age, education,
      residence, and income level created significant differences in the attitudes
      related to accepting gender roles and violence; and having an egalitarian
      attitude towards gender roles decreased the rate of accepting violence between
      the couples. Results indicate that premarital counseling is a promising strategy
      to support engaged couples' sexual/reproductive health needs, and increase their
      awareness about gender based couple violence in communities.

PMID- 29335811
TI  - Surgical stress response and promotion of metastasis in colorectal cancer: a
      complex and heterogeneous process.
AB  - Surgery remains the curative treatment modality for colorectal cancer in all
      stages, including stage IV with resectable liver metastasis. There is emerging
      evidence that the stress response caused by surgery as well as other
      perioperative therapies such as anesthesia and analgesia may promote growth of
      pre-existing micro-metastasis or potentially initiate tumor dissemination.
      Therapeutically targeting the perioperative period may therefore reduce the
      effect that surgical treatments have in promoting metastases, for example by
      combining beta-adrenergic receptor antagonists and cyclooxygenase-2 (COX-2)
      inhibitors in the perioperative setting. In this paper, we highlight some of the
      mechanisms that may underlie surgery-related metastatic development in colorectal
      cancer. These include direct tumor spillage at the time of surgery, suppression
      of the anti-tumor immune response, direct stimulatory effects on tumor cells, and
      activation of the coagulation system. We summarize in more detail results that
      support a role for catecholamines as major drivers of the pro-metastatic effect
      induced by the surgical stress response, predominantly through activation of beta
      adrenergic signaling. Additionally, we argue that an improved understanding of
      surgical stress-induced dissemination, and more specifically whether it impacts
      on the level and nature of heterogeneity within residual tumor cells, would
      contribute to the successful clinical targeting of this process. Finally, we
      provide a proof-of-concept demonstration that ex-vivo analyses of colorectal
      cancer patient-derived samples using RGB-labeling technology can provide
      important insights into the heterogeneous sensitivity of tumor cells to stress
      signals. This suggests that intra-tumor heterogeneity is likely to influence the
      efficacy of perioperative beta-adrenergic receptor and COX-2 inhibition, and that
      ex-vivo characterization of heterogeneous stress response in tumor samples can
      synergize with other models to optimize perioperative treatments and further
      improve outcome in colorectal and other solid cancers.

PMID- 29335812
TI  - Sperm telomere length in donor samples is not related to ICSI outcome.
AB  - PURPOSE: Variations in sperm telomere length (STL) have been associated with
      altered sperm parameters, poor embryo quality, and lower pregnancy rates, but for
      normozoospermic men, STL relevance in IVF/ICSI is still uncertain. Moreover, in
      all studies reported so far, each man's STL was linked to the corresponding
      female partner characteristics. Here, we study STL in sperm donor samples, each
      used for up to 12 women, in order to isolate and determine the relationship
      between STL and reproductive outcomes. METHODS: Relative STL was determined by
      qPCR in 60 samples used in a total of 676 ICSI cycles. Univariable and
      multivariable statistical analyses were used to study the STL effect on
      fertilization rate; embryo morphology; biochemical, clinical, and ongoing
      pregnancy rates; and live birth (LB) rates. RESULTS: The average STL value was
      4.5 (relative units; SD 1.9; range 2.4-14.2). Locally weighted scatterplot
      smoothing regression and the rho-Spearman test did not reveal significant
      correlations between STL and the outcomes analyzed. STL was not different between
      cycles resulting or not in pregnancy and LB (Mann-Whitney U test, p > 0.05). No
      significant effect of STL on reproductive outcomes was found, with the OR for
      each unit increase in STL (95% CI) of 0.94 (0.86-1-04), 0.99 (0.9-1.09), 0.98
      (0.89-1.09), and 0.93 (0.8-1.06) for biochemical, clinical, and ongoing pregnancy
      and LB, respectively. The multilevel analysis confirmed that the effect of STL on
      fertilization; biochemical, clinical, and ongoing pregnancy; and LB was not
      significant (p > 0.05). CONCLUSION: After addressing STL independently from
      female variables, results show that STL measurement is not useful to predict
      reproductive outcomes in ICSI cycles using donor semen.

PMID- 29335814
TI  - ?

PMID- 29335817
TI  - Repurposing existing drugs for new AMPK activators as a strategy to extend
      lifespan: a computer-aided drug discovery study.
AB  - Dietary restriction is one of the several ways which could putatively extend
      organisms' lifespan, ranging from Saccharomyces cerevisiae to rodents, by
      activating the AMP-activated protein kinase (AMPK), an ATP/AMP sensor. Extensive
      researches have shown that aging reduces sensibility of AMPK and eventually
      causes energy imbalance in cells. Research in mammals' AMPK depicts that this
      signaling molecule could control autophagy, improve cellular stress resistance
      and suppress inflammatory responses. Hence, in this study we performed a drug
      repurposing of 1908 FDA-approved drugs in order to discover putative safe
      activators of AMPK and to find new applications for existing drugs. For this
      purpose, FDA-approved drugs were screened by virtual screening and the ligand
      protein interactions were carefully inspected. Moreover, through MM/PBSA
      analysis, the binding affinity of hit compounds in gamma and alphabeta binding
      sites were investigated. As Cangrelor, Nacitentan, Levoleucovorin and Glisoxepide
      had lower binding affinities; we predicted that they would probably prove to be
      more potential activators than C2. However, hit-compounds in alphabeta binding
      site, exhibited higher unfavorable binding affinity. Hence, present findings can
      prove to be valuable for discovering new activators for AMPK.

PMID- 29335813
TI  - Organic acidurias in adults: late complications and management.
AB  - Organic acidurias (synonym, organic acid disorders, OADs) are a heterogenous
      group of inherited metabolic diseases delineated with the implementation of gas
      chromatography/mass spectrometry in metabolic laboratories starting in the 1960s
      and 1970s. Biochemically, OADs are characterized by accumulation of mono-, di-
      and/or tricarboxylic acids ("organic acids") and corresponding coenzyme A,
      carnitine and/or glycine esters, some of which are considered toxic at high
      concentrations. Clinically, disease onset is variable, however, affected
      individuals may already present during the newborn period with life-threatening
      acute metabolic crises and acute multi-organ failure. Tandem mass spectrometry
      based newborn screening programmes, in particular for isovaleric aciduria and
      glutaric aciduria type 1, have significantly reduced diagnostic delay. Dietary
      treatment with low protein intake or reduced intake of the precursor amino
      acid(s), carnitine supplementation, cofactor treatment (in responsive patients)
      and nonadsorbable antibiotics is commonly used for maintenance treatment.
      Emergency treatment options with high carbohydrate/glucose intake,
      pharmacological and extracorporeal detoxification of accumulating toxic
      metabolites for intensified therapy during threatening episodes exist. Diagnostic
      and therapeutic measures have improved survival and overall outcome in
      individuals with OADs. However, it has become increasingly evident that the
      manifestation of late disease complications cannot be reliably predicted and
      prevented. Conventional metabolic treatment often fails to prevent irreversible
      organ dysfunction with increasing age, even if patients are considered to be
      "metabolically stable". This has challenged our understanding of OADs and has
      elicited the discussion on optimized therapy, including (early) organ
      transplantation, and long-term care.

PMID- 29335816
TI  - Organ reserve, excess metabolic capacity, and aging.
AB  - "Organ reserve" refers to the ability of an organ to successfully return to its
      original physiological state following repeated episodes of stress. Clinical
      evidence shows that organ reserve correlates with the ability of older adults to
      cope with an added workload or stress, suggesting a role in the process of aging.
      Although organ reserve is well documented clinically, it is not clearly defined
      at the molecular level. Interestingly, several metabolic pathways exhibit excess
      metabolic capacities (e.g., bioenergetics pathway, antioxidants system,
      plasticity). These pathways comprise molecular components that have an excess of
      quantity and/or activity than that required for basic physiological demand in
      vivo (e.g., mitochondrial complex IV or glycolytic enzymes). We propose that the
      excess in mtDNA copy number and tandem DNA repeats of telomeres are additional
      examples of intrinsically embedded structural components that could comprise
      excess capacity. These excess capacities may grant intermediary metabolism the
      ability to instantly cope with, or manage, added workload or stress. Therefore,
      excess metabolic capacities could be viewed as an innate mechanism of
      adaptability that substantiates organ reserve and contributes to the cellular
      defense systems. If metabolic excess capacities or organ reserves are impaired or
      exhausted, the ability of the cell to cope with stress is reduced. Under these
      circumstances cell senescence, transformation, or death occurs. In this review,
      we discuss excess metabolic and structural capacities as integrated metabolic
      pathways in relation to organ reserve and cellular aging.

PMID- 29335818
TI  - Dorsal shaving affects concentrations of faecal cortisol metabolites in lactating
      golden hamsters.
AB  - Breeding of golden hamsters is classically performed at thermal conditions
      ranging from 20 to 24  degrees C. However, growing evidence suggests that
      lactating females suffer from heat stress. We hypothesised that shaving females
      dorsally to maximise heat dissipation may reduce stress during reproduction. We
      thus compared faecal cortisol metabolites (FCM) from shaved golden hamster
      mothers with those from unshaved controls. We observed significantly lower FCM
      levels in the shaved mothers (F1,22 = 8.69, p = 0.0075) pointing to lower stress
      due to ameliorated heat dissipation over the body surface. In addition, we
      observed 0.4  degrees C lower mean subcutaneous body temperatures in the shaved
      females, although this effect did not reach significance (F1,22 = 1.86, p =
      0.18). Our results suggest that golden hamsters having body masses being more
      than four times that of laboratory mice provide a very interesting model to study
      aspects of lactation and heat production at the same time.

PMID- 29335819
TI  - NMDA Receptor GluN2 Subtypes Control Epileptiform Events in the Hippocampus.
AB  - NMDA receptors (NMDARs) play a key role in synaptic plasticity and
      excitotoxicity. Subtype-specific role of NMDAR in neural disorders is an emerging
      area. Recent studies have revealed that mutations in NMDARs are a cause for
      epilepsy. Hippocampus is a known focal point for epilepsy. In hippocampus,
      expression of the NMDAR subtypes GluN1/GluN2A and GluN1/GluN2B is temporally
      regulated. However, the pharmacological significance of these subtypes is not
      well understood in epileptic context/models. To investigate this, epilepsy was
      induced in hippocampal slices by the application of artificial cerebrospinal
      fluid that contained high potassium but no magnesium. Epileptiform events (EFEs)
      were recorded from the CA1 and DG areas of hippocampus with or without subtype
      specific antagonists. Irrespective of the age group, CA1 and DG showed
      epileptiform activity. The NMDAR antagonist AP5 was found to reduce the number of
      EFEs significantly. However, the application of subtype-specific antagonists (TCN
      201 for GluN1/GluN2A and Ro 25-69811 for GluN1/GluN2B) revealed that EFEs had
      area-specific and temporal components. In slices from neonates, EFEs in CA1 were
      effectively reduced by Ro 25-69811, but were largely insensitive to TCN 201. In
      contrast, EFEs in DG were equally sensitive to both of the subtype-specific
      antagonists. However, the differential sensitivity for the antagonists observed
      in neonates was absent in later developmental stages. The study provides a
      functional insight into the NMDAR subtype-dependent contribution of EFEs in
      hippocampus of young rats, which may have implications in treating childhood
      epilepsy and avoiding unnecessary side effects of broad spectrum antagonists.

PMID- 29335820
TI  - How much do we know about hemolytic capability of pathogenic Candida species?
AB  - Hemolytic factor production by pathogenic Candida species is considered an
      important attribute in promoting survival within the mammal host through the
      ability to assimilate iron from the hemoglobin-heme group. Hemolytic capability
      has been evaluated for Candida species based on hemolysis zones on plate assay,
      analysis of hemolytic activity in liquid culture medium, and hemolysis from cell
      free culture broth. The production of hemolytic factor is variable among Candida
      species, where C. parapsilosis is the less hemolytic species. In general, no
      intraspecies differences in beta-hemolytic activities are found among isolates
      belonging to C. albicans, C. glabrata, C. krusei, C. tropicalis, and C.
      parapsilosis. The production of hemolytic factor by Candida species is affected
      by several factors such as glucose supplementation in the culture medium, blood
      source, presence of erythrocytes and hemoglobin, and presence of electrolytes. On
      the basis of existing achievements, more researches are still needed in order to
      extend our knowledge about the biochemical nature of hemolytic molecules produced
      by distinct Candida species, the mechanism of hemolysis, and the molecular basis
      of the hemolytic factor expression.

PMID- 29335821
TI  - Maternal incarceration, child protection, and infant mortality: a descriptive
      study of infant children of women prisoners in Western Australia.
AB  - BACKGROUND: There are no population statistics collected on a routine basis on
      the children of prisoners in Australia. Accordingly, their potential
      vulnerability to adverse outcomes remains unclear. This study draws on linked
      administrative data to describe the exposure of children aged less than 2 years
      to maternal imprisonment in Western Australia, their contact with child
      protection services, and infant mortality rates. RESULTS: In Western Australia,
      36.5 per 1000 Indigenous (n = 804) and 1.3 per 1000 non-Indigenous (n = 395)
      children born between 2001 and 2011 had mothers imprisoned after birth to age 2
      years. One-third of infants' mothers had multiple imprisonments (maximum of 11).
      Nearly half (46%) of prison stays were for <=2 weeks, 12% were between 2 and 4
      weeks, 14% were for 1-3 months, and 28% were longer than three months.
      Additionally, 17.4 per 1000 Indigenous (n = 383) and 0.5 per 1000 non-Indigenous
      (n = 150) children had mothers imprisoned during pregnancy. Half of the children
      with a history of maternal incarceration in pregnancy to age 2 years came into
      contact with child protection services by their second birthday, with 31% of
      Indigenous and 35% of non-Indigenous children entering out-of-home care. Rates of
      placement in care were significantly higher for Indigenous children (Relative
      Risk (RR) 27.30; 95%CI 19.19 to 38.84; p < .001) and for non-Indigenous children
      (RR 110.10; 95%CI 61.70 to 196.49; p < .001) with a history of maternal
      imprisonment compared to children of mothers with no corrections record. Infant
      mortality for children whose mothers were imprisoned up to 5 years before birth
      or within their first year after birth was higher than for children of mothers
      with no corrections record for both Indigenous (RR 2.36; 95%CI 1.41 to 3.95; p =
      .001) and non-Indigenous children (RR 2.28; 95%CI 0.75 to 6.97; p = .147).
      CONCLUSIONS: This study highlights the particular vulnerability of children whose
      mothers have been incarcerated and the importance of considering their needs
      within corrective services policies and procedures. Prison may present an
      opportunity to identify and work with vulnerable families to help improve
      outcomes for children as well as mothers.

PMID- 29335822
TI  - Emergency department throughput: an intervention.
AB  - Shortening emergency department (ED) boarding time and managing hospital bed
      capacity by expediting the inpatient discharge process have been challenging for
      hospitals nationwide. The objective of this study is was to explore the effect of
      an innovative prospective intervention on hospital workflow, specifically on
      early inpatient discharges and the ED boarding time. The intervention consisted
      of a structured nursing "admission discharge transfer" (ADT) protocol receiving
      new admissions from the ED and helping out floor nursing with early discharges.
      ADT intervention was implemented in a 38-bed hospitalist run inpatient unit at an
      academic hospital. The study population consisted of 4486 patients (including
      inpatient and observation admissions) who were hospitalized to the medicine unit
      from March 2013-March 2014. Of these hospitalizations, 2259 patients received the
      ADT intervention. Patients' demographics, discharge and ED boarding data were
      collected for from March 4, 2013 to March 31, 2014 for both intervention and
      control groups (28 weeks each). Chi-square and unpaired t tests were utilized to
      compare population characteristics. Poisson regression analysis was conducted to
      estimate the association between intervention and hospital length of stay
      adjusted for differences in patient demographics. Mean age of the study
      population was 58.6 years, 23% were African Americans and 55% were women. A
      significant reduction in ED boarding time (p < 0.001) and improvement in early
      (before 2 PM) hospital discharges (p = 0.01) were noticed among patients in the
      intervention groups. There was a slight but significant reduction in hospital
      length of stay for observation patients in the intervention group; however, no
      such difference was noted for inpatient admissions. Our study showed that
      dedicating nursing resources towards ED-boarded patients and early inpatient
      discharges can significantly improve hospital workflow and reduce hospital length
      of stay.

PMID- 29335823
TI  - [Drugs for intravenous induction of anesthesia: propofol].
AB  - In a series of articles dealing with hypnotics for induction of anesthesia, this
      article describes the development and current value of propofol. Its significance
      far exceeds that of a pure induction hypnotic (sedation in diagnostic and
      therapeutic procedures and on the intensive care unit). Propofol is also used for
      sedation in diagnostic and therapeutic procedures and on the intensive care unit.
      In the field of induction of anesthesia, the alternatives are barely used. Some
      contraindications are still controversial whereas others are no longer
      sufficiently anchored in the users' awareness (widespread off-label use). Adverse
      effects, such as injection pain, infection risk and propofol-related infusion
      syndrome (PRIS) could be significantly reduced by pharmacovigilance. With
      appropriate caution nearly the whole spectrum of anesthesiology patients can be
      treated using propofol. The hemodynamic side effects and the rare but potentially
      fatal PRIS are limitations. Further developments address the water solubility and
      the solubilizing agents of propofol.

PMID- 29335824
TI  - Broad-spectrum resistance of Pseudomonas aeruginosa from shellfish: infrequent
      acquisition of novel resistance mechanisms.
AB  - Pseudomonas aeruginosa is one the most common multidrug-resistant pathogens
      worldwide. It has been previously detected in marine shellfish, but its
      antibiotic resistance in such environment has not been explored. By combining PCR
      detection of acquired genes, and resistance-nodulation-cell division (RND) efflux
      studying, we investigated the multifactorial resistance traits of 108 P.
      aeruginosa isolates recovered from wild-growing Mediterranean mussels (Mytilus
      galloprovincialis) in Croatia. Eleven different resistance profiles were found,
      with the main mechanism being the overexpression of intrinsic efflux pump(s),
      particularly MexAB-OprM. Several acquired resistance determinants were detected,
      including the beta-lactamase gene blaTEM-116, sulfamethoxazole resistance gene
      sul1, and the class 1 integron gene cassette carrying the streptomycin resistance
      gene aadA7. This study evidenced the multiple resistance in P. aeruginosa in
      shellfish from human-impacted marine environment, pointing to the underestimated
      role of the marine habitat for maintenance of multiresistant P. aeruginosa and,
      consequently, the potential risk for human and environmental health.

PMID- 29335825
TI  - Application of artificial intelligence using a convolutional neural network for
      detecting gastric cancer in endoscopic images.
AB  - BACKGROUND: Image recognition using artificial intelligence with deep learning
      through convolutional neural networks (CNNs) has dramatically improved and been
      increasingly applied to medical fields for diagnostic imaging. We developed a CNN
      that can automatically detect gastric cancer in endoscopic images. METHODS: A CNN
      based diagnostic system was constructed based on Single Shot MultiBox Detector
      architecture and trained using 13,584 endoscopic images of gastric cancer. To
      evaluate the diagnostic accuracy, an independent test set of 2296 stomach images
      collected from 69 consecutive patients with 77 gastric cancer lesions was applied
      to the constructed CNN. RESULTS: The CNN required 47 s to analyze 2296 test
      images. The CNN correctly diagnosed 71 of 77 gastric cancer lesions with an
      overall sensitivity of 92.2%, and 161 non-cancerous lesions were detected as
      gastric cancer, resulting in a positive predictive value of 30.6%. Seventy of the
      71 lesions (98.6%) with a diameter of 6 mm or more as well as all invasive
      cancers were correctly detected. All missed lesions were superficially depressed
      and differentiated-type intramucosal cancers that were difficult to distinguish
      from gastritis even for experienced endoscopists. Nearly half of the false
      positive lesions were gastritis with changes in color tone or an irregular
      mucosal surface. CONCLUSION: The constructed CNN system for detecting gastric
      cancer could process numerous stored endoscopic images in a very short time with
      a clinically relevant diagnostic ability. It may be well applicable to daily
      clinical practice to reduce the burden of endoscopists.

PMID- 29335827
TI  - Satisfactory arterial repair 1 year after ultrathin strut biodegradable polymer
      sirolimus-eluting stent implantation: an angioscopic observation.
AB  - The ultrathin strut biodegradable polymer sirolimus-eluting stent (Orsiro, O-SES)
      exhibits satisfactory clinical outcomes. However, no report to date has
      documented the intravascular status of artery repair after O-SES implantation. We
      examined 5 O-SES placed in 4 patients (age 65 +/- 12 years, male 75%) presenting
      with stable angina pectoris due to de novo lesions in native coronary arteries.
      Coronary angioscopy was performed immediately after percutaneous coronary
      intervention and 1 year later. Angioscopic images were analyzed to determine the
      following: (1) dominant grade of neointimal coverage (NIC) over the stent; (2)
      maximum yellow plaque grade; and (3) existence of thrombus. Yellow plaque grade
      was evaluated both immediately after stent implantation and at the time of follow
      up observation. The other parameters were evaluated at the time of follow-up
      examination. NIC was graded as: grade 0, stent struts exposed; grade 1, struts
      bulging into the lumen, although covered; grade 2, struts embedded in the
      neointima, but translucent; grade 3, struts fully embedded and invisible. Yellow
      plaque severity was graded as: grade 0, white; grade 1, light yellow; grade 2,
      yellow; and grade 3, intensive yellow. Angioscopic findings at 1 year
      demonstrated the following: dominant NIC grade 1, grade 2, and grade 3 in 1, 2,
      and 2 stents, respectively; all stents were covered to some extent; focal
      thrombus adhesion was observed in only 1 stent. Yellow plaque grade did not
      change from immediately after stent implantation to follow-up. O-SES demonstrated
      satisfactory arterial repair 1 year after implantation.

PMID- 29335826
TI  - High-salt- and cholesterol diet-associated cognitive impairment attenuated by
      tannins-enriched fraction of Emblica officinalis via inhibiting NF-kB pathway.
AB  - Metabolic disorders are closely associated with dietary habits and seem to be
      related to neuroinflammation and neurodegenerative disease in humans. Emblica
      officinalis (EOT) fruits not only have good nutritional value but also have
      excellent therapeutic potential. We used a tannins-enriched fraction of EOT fruit
      with the expectation of controlling diet-induced neuroinflammation and cognitive
      impairment in rats. A high-salt and cholesterol diet (HSCD) was used to induce
      neuroinflammation and cognitive impairment in rats. The diet of the rats was then
      supplemented with EOT (100 and 200 mg/kg b.w.) for 7 weeks. In order to evaluate
      the neuroprotective effects of EOT; in silico study, neurobehavioral tests,
      biochemical analyses, and immunohistochemical studies were performed. In silico
      study of p50 (NF-kappaB1) receptors with emblicanin (the main constituent of EOT)
      suggests that EOT has binds to NF-kappaB. EOT treatment reversed the HSCD-induced
      behavioral and memory disturbances in a step-down-type passive avoidance test.
      EOT treatment also inhibited HSCD-induced NF-kappaB upstream signaling, including
      the release of Th1, such as TNF-alpha, and downstream signaling Th2, such as IL
      10, by flow cytometer. In addition, EOT treatment attentuated the HSCD-induced
      increase in the level of cognitive impairment markers, such as amyloid beta.
      Furthermore, immunohistochemical results demonstrated that EOT modulated neuronal
      cell death by inhibiting the overexpression of NF-kB in brain. This study
      confirms that EOT may be a promising therapy in ameliorating the neurotoxicity of
      HSCD; however further studies are warranted to elucidate the exact mechanism of
      action of EOT.

PMID- 29335828
TI  - Low, but Not High, Doses of Copper Sulfate Impair Synaptic Plasticity in the
      Hippocampal CA1 Region In Vivo.
AB  - Previous studies have shown the inhibitory effect of the in vitro application of
      copper sulfate on hippocampal long-term potentiation. While in vivo
      administration of copper did not affect spatial learning and memory. To find
      possible answers to this controversial issue, we evaluate the effect of different
      doses of copper sulfate on in vivo long-term potentiation, synaptic transmission,
      and paired-pulse behavior of CA1 pyramidal cells. Thirty-two male Wistar rats
      were divided into four groups: control, 5, 10, and 15 mg of copper sulfate. Field
      excitatory postsynaptic potential from the stratum radiatum of CA1 neurons was
      recorded following Schaffer collateral stimulation in rats. Spike amplitude, long
      term potentiation and paired-pulse index were measured in all groups. The results
      of this study showed that 5 mg/kg copper sulfate increased synaptic transmission
      and inhibited long-term potentiation and decreased the hippocampal paired-pulse
      ratio, while 10 and 15 mg/kg copper sulfate did not affect CA1 synaptic
      transmission properties. Low, but not high, doses of copper sulfate affect
      synaptic plasticity. This finding may explain the difference between the effect
      of copper on synaptic plasticity and spatial learning and memory.

PMID- 29335829
TI  - Pancreaticoduodenectomy for periampullary tumours: a review article based on
      Surveillance, End Results and Epidemiology (SEER) database.
AB  - INTRODUCTION: This study set to examine relative survival of patients with
      periampullary cancers undergoing pancreaticoduodenectomy (PD). METHODS: Using the
      Surveillance, End Results and Epidemiology (SEER) database, this study identified
      9877 patients with non-metastatic pancreatic adenocarcinoma who underwent PD
      between 2004 and 2013. RESULTS: Ampullary carcinomas have the best survival among
      periampullary malignancies. Lymph node ratio is a significant prognostic factor,
      even when stratified by tumour types. Patients receiving adjuvant radiotherapy
      following PD have superior survival than patients without radiotherapy (median 25
      vs 20 months, p < 0.001), particularly ductal adenocarcinoma (HR: 0.74, CI95%
      0.69-0.78; p < 0.001), cholangiocarcinoma (HR: 0.75, CI95% 0.59-0.97; p = 0.027),
      and ampullary carcinoma (HR: 0.79, CI95% 0.64-0.98; p = 0.029) with greatest
      survival benefit at 1-year postresection. CONCLUSION: Future studies aiming to
      further define genetic signatures of individual periampullary cancers would allow
      a personalised therapeutic approach in improving survival.

PMID- 29335830
TI  - From imaging to biology of glioblastoma: new clinical oncology perspectives to
      the problem of local recurrence.
AB  - GBM is one of the most common and aggressive brain tumors. Surgery and adjuvant
      chemoradiation have succeeded in providing a survival benefit. Although most
      patients will eventually experience local recurrence, the means to fight
      recurrence are limited and prognosis remains poor. In a disease where local
      control remains the major challenge, few trials have addressed the efficacy of
      local treatments, either surgery or radiation therapy. The present article
      reviews recent advances in the biology, imaging and biomarker science of GBM as
      well as the current treatment status of GBM, providing new perspectives to the
      problem of local recurrence.

PMID- 29335832
TI  - Lateral trochanteric pain following total hip arthroplasty: radiographic
      assessment of altered biomechanics as a potential aetiology.
AB  - INTRODUCTION: Lateral trochanteric pain (LTP) complicates up to 17% of cases of
      total hip arthroplasty (THA). Studies have refuted underlying trochanteric
      bursitis. Restoration of the femoral offset and reproduction of the natural
      femoral centre of rotation are important in successful arthroplasty. LTP is
      believed to be associated with their alteration. AIM: The aim of our study was to
      evaluate the effect of femoral offset and centre of rotation on the incidence of
      LTP post-THA. METHODS: A retrospective case control study was developed from 158
      patients who underwent a THA over a two-year period to form two patient cohorts.
      Twenty-nine patients diagnosed with LTP were matched with 110 control subjects.
      The direct lateral approach was used in all cases. Anterior-posterior pelvic
      radiographs before and after surgery were compared to assess the femoral, cup and
      global offsets and limb length discrepancies between the two groups. Statistical
      analyses were performed using the Mann-Whitney U test and independent samples t
      test. RESULTS: Twenty-nine diagnosed with post-operative LTP. Sixty-two percent
      of symptomatic patients were female (p = 0.13). The median ages were 74.33
      (symptomatic) and 70.71 (control) (p = 0.11). The differences (pre-post) of the
      femoral (p = 0.17), cup (p = 0.5) and global offsets (p = 0.99) and mean of limb
      length discrepancy (LLD) (p = 0.83) were not significant between the two groups.
      CONCLUSION: No relationship was found between LTP and femoral offset or femoral
      centre of rotation. Disruption of the soft tissues during a lateral approach with
      resultant abductor tear, tendon defects and tendinitis might play a role in LTP
      and explain the apparent efficacy of corticosteroid injections.

PMID- 29335833
TI  - Regulation of Bone Metabolism by microRNAs.
AB  - PURPOSE OF REVIEW: The small non-coding microRNAs (miRNAs) have emerged as
      important post-transcriptional regulators of various physiological and
      pathological processes. The purpose of this article is to review the important
      recent advances on the role of miRNAs in bone remodeling and metabolic bone
      disorders. RECENT FINDINGS: In a physiological context, miRNAs regulate bone
      formation and bone resorption, thereby contributing to the maintenance of bone
      homeostasis. Under pathological conditions, an aberrant miRNA signaling
      contributes to the onset and progression of skeletal disorders, such as
      osteoporosis. Furthermore, miRNAs can be secreted to circulation and have
      clinical potential as non-invasive biomarkers. In a therapeutic setting, miRNA
      delivery or antagonism has been reported to affect several diseases under pre
      clinical conditions thereby emerging as novel pharmacological tools. miRNAs are
      key regulators of bone remodeling in health and disease. The future perspectives
      in the field include the role of secreted miRNAs in cell-cell communication in
      the bone environment. Furthermore, the clinical potential of using miRNAs as
      diagnostic tools and therapeutic targets to treat metabolic bone diseases
      provides an attractive future direction.

PMID- 29335831
TI  - Quality of inter-hospital transportation in 431 transport survivor patients
      suffering from acute respiratory distress syndrome referred to specialist
      centers.
AB  - BACKGROUND: The acute respiratory distress syndrome (ARDS) is a life-threatening
      condition. In special situations, these critically ill patients must be
      transferred to specialized centers for escalating treatment. The aim of this
      study was to evaluate the quality of inter-hospital transport (IHT) of ARDS
      patients. METHODS: We evaluated medical and organizational aspects of structural
      and procedural quality relating to IHT of patients with ARDS in a prospective
      nationwide ARDS study. The qualification of emergency staff, the organizational
      aspects and the occurrence of critical events during transport were analyzed.
      RESULTS: Out of 1234 ARDS patients, 431 (34.9%) were transported, and 52 of these
      (12.1%) treated with extracorporeal membrane oxygenation. 63.1% of transferred
      patients were male, median age was 54 years, and 26.8% of patients were obese.
      All patients were mechanically ventilated during IHT. Pressure-controlled
      ventilation was the preferred mode (92.1%). Median duration to organize the IHT
      was 165 min. Median distance for IHT was 58 km, and median duration of IHT 60
      min. Forty-two patient-related and 8 technology-related critical events (11.6%,
      50 of 431 patients) were observed. When a critical event occurred, the PaO2/FiO2
      ratio before transport was significant lower (68 vs. 80 mmHg, p = 0.017). 69.8%
      of physicians and 86.7% of paramedics confirmed all transfer qualifications
      according to requirements of the German faculty guidelines (DIVI). CONCLUSIONS:
      The transport of critically ill patients is associated with potential risks. In
      our study the rate of patient- and technology-related critical events was
      relatively low. A severe ARDS with a PaO2/FiO2 ratio < 70 mmHg seems to be a risk
      factor for the appearance of critical events during IHT. The majority of
      transport staff was well qualified. Time span for organization of IHT was
      relatively short. ECMO is an option to transport patients with a severe ARDS
      safely to specialized centers. Trial registration NCT02637011
      (ClinicalTrials.gov, Registered 15 December 2015, retrospectively registered).

PMID- 29335835
TI  - Etiology of invasive candidosis agents in Russia: a multicenter epidemiological
      survey.
AB  - A multicenter prospective epidemiological survey on the etiologic agents of
      invasive candidosis was conducted in Russia in the period of 2012-2014. Samples
      were collected from 284 patients with invasive candidosis and Candida species
      isolated by culture. The species were identified by DNA sequencing and MALDI-TOF
      massspectrometry. A total of 322 isolates were recovered, in which 96% of Sandida
      species belonged to six major species, namely, C. albicans (43.2%), C.
      parapsilosis (20.2%), C. glabrata (11.5%), C. tropicalis (9.6%), C. krusei
      (6.2%), and C. guilliermondii (5.3%). Most Candida species were isolated from
      blood samples (83.23%). Notably, the prevalence rate of C. albicans reduced from
      52.38% to 32.79% (2012 vs. 2014) (P = 0.01) whereas that of non-C. albicans
      increased from 47.62% (2012) to 67.21% (2014) (P < 0.01). Species distribution
      differed among geographical regions; specifically, the prevalence rate of C.
      albicans as an etiologic agent of invasive candidosis in Siberian Federal region
      was significantly higher than that in other Federal regions. Results indicated a
      shift from C. albicans to non-C. albicans. Therefore, a detailed investigation on
      the contributing factors and appropriate treatment of invasive candidosis is
      needed.

PMID- 29335834
TI  - Genetics of Osteopetrosis.
AB  - PURPOSE OF REVIEW: The term osteopetrosis refers to a group of rare skeletal
      diseases sharing the hallmark of a generalized increase in bone density owing to
      a defect in bone resorption. Osteopetrosis is clinically and genetically
      heterogeneous, and a precise molecular classification is relevant for prognosis
      and treatment. Here, we review recent data on the pathogenesis of this disorder.
      RECENT FINDINGS: Novel mutations in known genes as well as defects in new genes
      have been recently reported, further expanding the spectrum of molecular defects
      leading to osteopetrosis. Exploitation of next-generation sequencing tools is
      ever spreading, facilitating differential diagnosis. Some complex phenotypes in
      which osteopetrosis is accompanied by additional clinical features have received
      a molecular classification, also involving new genes. Moreover, novel types of
      mutations have been recognized, which for their nature or genomic location are at
      high risk being neglected. Yet, the causative mutation is unknown in some
      patients, indicating that the genetics of osteopetrosis still deserves intense
      research efforts.

PMID- 29335836
TI  - Adipogenesis and lipid production in adipocytes subjected to sustained tensile
      deformations and elevated glucose concentration: a living cell-scale model system
      of diabesity.
AB  - Adipocyte fate commitment is characterized by morphological changes of
      fibroblastic pre-adipocyte cells, and specifically by accumulation of lipid
      droplets (LDs) as part of the adipogenesis metabolism. Formation of LDs indicates
      the production of triglycerides from glucose through an insulin-regulated glucose
      internalization process. In obesity, adipocytes typically become insulin
      resistant, and glucose transport into the cells is impaired, resulting in type 2
      diabetes. In the present study, we monitored the adipogenesis in 3T3-L1 cultured
      cells exposed to high (450 mg/dL hyperglycemia) and low (100 mg/dL physiological)
      glucose concentrations, in a novel cell culture model system of diabesity. In
      addition to glucose conditions, cells were concurrently exposed to different
      substrate tensile strains (12% and control) based on our prior work which
      revealed that adipogenesis is accelerated in cultures subjected to static,
      chronic substrate tensile deformations. Phase-contrast images were taken
      throughout the adipogenesis process (3 weeks) and were analyzed by an image
      processing algorithm which quantitatively monitors cell differentiation and lipid
      accumulation (number of LDs per cell and their radius as well as cell size and
      shape). The results indicated that high glucose concentrations and substrate
      tensile strains delivered to adipocytes accelerated lipid production by 1.7- and
      1.4-fold, respectively. In addition, significant changes in average cell
      projected area and in other morphological attributes were observed during the
      differentiation process. The importance of this study is in characterizing the
      adipogenesis parameters as potential read-outs that can predict the occurrence of
      insulin resistance in the development of diabesity.

PMID- 29335837
TI  - Backbone chemical shift assignments of the glycine cleavage complex H protein of
      Escherichia coli.
AB  - Glycine cleavage complex H protein (GcvH) is one of the four components that form
      the glycine cleavage complex (GCS), essential for the synthesis of C1 (one-carbon
      units) for cell metabolism, by the oxidative cleavage of glycine. The activity of
      this complex is induced in the presence of exogenous glycine, and is repressed by
      purines. GCS, in cooperation with GCA (serine hydroxymethyltransferase) regulates
      the endogenous levels of glycine and C1 units in the cell. GcvH, the lipoamide
      containing component of the complex, plays an indispensable role in this
      reaction, as its prosthetic group shuttles between the active site of the three
      other components of the GCS complex sequentially. In environments rich in
      exogenous lipoic acid, GcvH is converted to lipoyl-GcvH by Lipoate protein ligase
      (LplA), by the salvage pathway. When exogenous lipoic acid is deficient, it is
      post-translationally modified to lipoyl-GcvH by the consecutive action of two
      enzymes, (a) Lipoate protein ligase B (LipB) and (b) Lipoyl synthase (LipA).
      Although, the crystal structure has been determined for Escherichia coli GcvH, no
      information exists for its interaction with LipB or LipA. Therefore, we plan to
      study its interactions with the aforementioned enzymes. As a first step, we have
      carried out the complete backbone chemical shift assignments of the E. coli
      glycine cleavage complex H protein in its apo-form, as well as its C8-
      intermediate.

PMID- 29335839
TI  - Successful replacement of the longest worldwide in situ Nanostim leadless cardiac
      pacemaker for a Micra Transcatheter Pacing System.

PMID- 29335838
TI  - Effect of immunonutrition on colorectal cancer patients undergoing surgery: a
      meta-analysis.
AB  - PURPOSE: Immunonutrition has been used to prevent the complications after
      colorectal elective surgery. This systematic review aimed to analyze and assess
      the effect of immunonutrition on colorectal cancer patients who received elective
      surgery. METHODS: Three electronic databases (Medline, Embase, Cochrane) were
      used to search the latent studies which investigated the effects of enteral
      immunonutrition (EIN) compared with standard enteral nutrition (EN) or parenteral
      immunonutrition (PIN) compared with standard parenteral nutrition (PN) on
      colorectal cancer patients who are undergoing surgery until 21st of April, 2017.
      Meta-analysis was conducted to calculate odd risk (OR), mean difference (MD), or
      standard mean difference (SMD) with 95% confidence interval (CI), and
      heterogeneity was tested by Q test. RESULTS: Nine publications were included. The
      meta-analysis results presented that EIN improved the length of hospital stay
      (pooled MD, 2.53; 95% CI, 1.29-3.41), infectious complications (pooled OR, 0.33;
      95% CI, 0.21-0.53) which contains the Surgical Site Infections (pooled OR, 0.25;
      95% CI, 0.22-0.58) and Superficial/Deep incisional infections (pooled OR, 0.27;
      95% CI, 0.12-0.64); meanwhile, PIN improved the length of hospital stay (pooled
      MD, 2.66; 95% CI, 0.62-4.76), IL-6 (pooled MD, - 6.09; 95% CI, - 10.11 to -
      2.07), CD3 (pooled MD, 7.50; 95% CI, 3.57-11.43), CD4 (pooled MD, 5.47; 95% CI,
      2.54-8.40), and CD4/CD8 (pooled MD, 0.50; 95% CI, 0.22-0.78); the level of CD8
      was lower (pooled MD, - 4.32; 95% CI, - 7.09 to - 1.55) in PIN. CONCLUSION:
      Immunonutrition could be an effective approach to enhance the immune function of
      colorectal cancer patients undergoing elective surgery and to improve the
      clinical and laboratory outcomes.

PMID- 29335840
TI  - Efficacy of ultrasound-guided axillary/subclavian venous approaches for pacemaker
      and defibrillator lead implantation: a randomized study.
AB  - PURPOSE: Subclavian access is a reliable technique for lead insertion in
      pacemaker and defibrillator (ICD) implantation, but it is often accompanied by
      complications. The aim of this study was to compare the efficacy of the
      ultrasound-guided axillary approach to the subclavian method. METHODS: This
      randomized comparative study was performed on 174 patients: as a first attempt,
      116 patients underwent the ultrasound-guided axillary access and 58 patients
      underwent the subclavian approach. A total of 364 leads were placed. Operators
      were trained in ultrasound-guided vein access technique. RESULTS: Axillary access
      was successful in 69% of patients (32/46), in the training phase and, as a first
      attempt, in 91.4% of patients (106/116), in the randomized phase. When axillary
      approach failed, we performed the following: subclavian access in 5.2% of
      patients (6/116), cephalic approach in 2.6% of patients (3/116), surgical method
      in 0.9% of patients (1/116). The subclavian technique was effective, as a first
      attempt, in 55 patients (94.8%). When the subclavian access failed, the
      ultrasound axillary approach successfully performed in all three cases. During a
      mean follow-up of 18 +/- 6 months, the number of lead complications was similar
      in the subclavian group compared to the axillary group (p = 0.664). CONCLUSIONS:
      As first attempt, ultrasound-guided axillary method showed similarly high-success
      rate than subclavian approach and well performed when the first attempt in
      subclavian group failed. Axillary access can be considered a safe and effective
      alternative technique to the conventional subclavian method for device
      implantation.

PMID- 29335842
TI  - Direct repression of IGF2 is implicated in the anti-angiogenic function of
      microRNA-210 in human retinal endothelial cells.
AB  - Pathological angiogenesis leads to the development of retinal vasculopathies and
      causes severe vision impairment. Increased understanding of the mechanisms
      underlying the angiogenic behavior of retinal endothelial cells helps provide new
      insights for developing treatment of retinal vasculopathies. Pro-angiogenic
      function of miR-210 has previously been identified. However, the functional
      implication of miR-210 in retinal endothelial cells remains unknown. Human
      retinal microvascular endothelial cells (HRECs) were employed to investigate the
      impact of miR-210 on the angiogenic capacity of retinal endothelial cells. It was
      observed that without affecting the viability of HRECs, miR-210 significantly
      suppressed the migration and capillary-like tube formation in HRECs. Moreover,
      pro-angiogenic insulin growth factor 2 (IGF2) was newly identified as a direct
      target of miR-210 in HRECs. MiR-210 decreased the expression of IGF2 at both mRNA
      and protein levels in HRECs. IGF2-simulated activation of p38 MAPK was attenuated
      by miR-210 in HRECs. Recombinant IGF2 protein rescued miR-210-induced impairment
      of tube formation in HRECs. Therefore, in contrast to the previously reported pro
      angiogenic function of miR-210, the current work reveals novel anti-angiogenic
      activity of miR-210 in HRECs. Furthermore, IGF2 is identified for the first time
      as a direct target of miR-210 in HRECs, adding new mechanistic insights into the
      expression regulation of pro-angiogenic IGF2 in human retinal endothelial cells.
      The current work helps increase the understanding of regulatory mechanisms
      underlying retinal endothelial cell physiology, justifying further evaluation for
      the therapeutic implications of miR-210/IGF2 interaction in the treatment of
      related retinal vasculopathies.

PMID- 29335841
TI  - Reconstructing normality following the diagnosis of a childhood chronic disease:
      does "rare" make a difference?
AB  - : Living with a childhood chronic disease can be challenging, especially if the
      diagnosis involves a rare condition. This study sought to elucidate how the
      diagnosis of a rare disease, as compared to a common, chronic condition, may
      influence maternal experiences of childhood illness. We conducted face-to-face,
      semi-structured interviews with 26 mothers of children treated in a pediatric
      hospital in the province of Lecco, Italy. Half of the participants had a child
      diagnosed with Bartter syndrome (BS), and the rest had a child suffering from
      celiac disease (CD). Interviews were recorded, transcribed, and analyzed using an
      inductive thematic approach. We identified three main themes from the analysis of
      our data: (1) disrupted normality and the need to know, (2) reconstructing
      normality, and (3) acting "normal." Although most participants experienced the
      disclosure of diagnosis as a relief, processes that facilitated normality
      reconstruction in celiac families, notably access to appropriate information,
      social support, and personal contact with comparison others, were found to be
      important stressors for mothers living with BS. CONCLUSION: This comparative
      qualitative study provides evidence on how well-known problems associated with
      the rarity of childhood diseases impact on families' efforts to cope with the
      illness and regain a sense of normality. What is Known: * Families living with a
      rare disease have been found to experience a range of common problems, directly
      linked to the rarity of these pathologies. What is New: * Maximization of both
      emotional and instrumental social support, through provision of appropriate
      information or establishment of disease-specific support groups, could greatly
      contribute to rare disease families' efforts to cope with childhood illness and
      regain a sense of normality.

PMID- 29335843
TI  - Study on the Clinical Features and Prognosis of Penicilliosis marneffei Without
      Human Immunodeficiency Virus Infection.
AB  - OBJECTIVE: To improve the diagnosis and treatment of Penicilliosis marneffei
      without human immunodeficiency virus infection. METHODS: Analyze and review the
      clinical features, diagnosis and treatment of six cases of P. marneffei without
      human immunodeficiency virus infection at The First Affiliated Hospital of Fujian
      Medical University. RESULTS: Two cases were diagnosed in the ENT Department,
      three cases in the respiratory department and one case in the dermatological
      department. Penicillium marneffei infection was confirmed by sputum culture,
      blood culture and tissue biopsy. After definite diagnosis, one refused further
      treatment, and others showed significant improvement. CONCLUSION: Penicilliosis
      marneffei is insidious onset and easy to be escaped and misdiagnosed. To achieve
      early diagnosis and appropriate treatment, doubtful cases should be alerted for
      the diagnoses as P. marneffei.

PMID- 29335844
TI  - The Adiponectin Homolog Osmotin Enhances Neurite Outgrowth and Synaptic
      Complexity via AdipoR1/NgR1 Signaling in Alzheimer's Disease.
AB  - Alzheimer's disease is a major neurodegenerative disease characterized by memory
      loss and cognitive deficits. Recently, we reported that osmotin, which is a
      homolog of adiponectin, improved long-term potentiation and cognitive functions
      in Alzheimer's disease mice. Several lines of evidence have suggested that Nogo-A
      and the Nogo-66 receptor 1 (NgR1), which form a complex that inhibits long-term
      potentiation and cognitive function, might be associated with the adiponectin
      receptor 1 (AdipoR1), which is a receptor for osmotin. Here, we explore whether
      osmotin's effects on long-term potentiation and memory function are associated
      with NgR1 signaling via AdipoR1 in Alzheimer's disease. Osmotin reduced the
      expression of NgR1 without affecting Nogo-A expression. Furthermore, osmotin
      inhibited NgR1 signaling by prohibiting the formation of the Nogo-A and NgR1
      ligand-receptor complex, resulting in enhanced neurite outgrowth; these effects
      disappeared in the presence of AdipoR1 interference. In addition, osmotin
      increased the expression of the pre- and postsynaptic markers synaptophysin and
      PSD-95, as well as the activation of the memory-associated markers AMPA receptor
      and CREB; these effects occurred in an AdipoR1- and NgR1-dependent manner.
      Osmotin was also found to enhance dendritic complexity and spine density in the
      hippocampal region of Alzheimer's disease mouse brains. These results suggest
      that osmotin can enhance neurite outgrowth and synaptic complexity through
      AdipoR1 and NgR1 signaling, implying that osmotin might be an effective
      therapeutic agent for Alzheimer's disease and that AdipoR1 might be a crucial
      therapeutic target for neurodegenerative diseases such as Alzheimer's.

PMID- 29335847
TI  - Diabetes, Obesity, and the Metabolic Syndrome as Prognostic Factors in Stages I
      to III Colorectal Cancer Patients.
AB  - BACKGROUND: Attempts to introduce prognostic factors for survival outcomes in
      localized colorectal cancer patients receiving surgical treatment with or without
      adjuvant therapies, beyond the classic staging parameters, have been met with
      limited success. Obesity and diabetes mellitus are among the conditions that
      predispose to colorectal cancer but their value as prognostic markers once the
      disease is diagnosed is controversial. PATIENTS AND METHODS: This study examines
      the prognostic value of the components of metabolic syndrome in a retrospective
      series of colorectal cancer patients with stages I to III disease followed in a
      single center. RESULTS: Among the four components of the metabolic syndrome, only
      diabetes was independently associated with progression-free survival (PFS) while
      obesity, hypertension, and dyslipidemia were not. No associations of the
      metabolic syndrome (MS) or its components with overall survival (OS) were
      observed in multivariate analysis. CONCLUSION: These data pinpoint to diabetes
      mellitus (DM) as a possible prognostic factor for PFS in localized colorectal
      cancer and further cast doubt for the value of obesity as measured by body mass
      index (BMI) on local stage colorectal cancer prognosis.

PMID- 29335849
TI  - Differential expression of adipokines in knee osteoarthritis patients with and
      without metabolic syndrome.
AB  - PURPOSE: The purpose of this study was to compare adipokines levels in plasma and
      synovial fluid (SF) between knee osteoarthritis (OA) patients with and without
      metabolic syndrome (MetS), and to evaluate the associations between adipokines
      levels and clinical severity of knee osteoarthritis. METHODS: Eighty female
      patients with knee osteoarthritis were enrolled in the study. These patients were
      divided into two groups: patients with and without MetS. Clinical severity was
      evaluated according to visual analogue scale (VAS) pain scores and Western
      Ontario McMaster University Osteoarthritis Index (WOMAC) scores. Adipokines and
      soluble leptin receptor levels in plasma and SF were determined by a sandwich
      enzyme-linked immunosorbent assay. RESULTS: Forty-three (54%) osteoarthritis
      patients with MetS and 37 (46%) osteoarthritis patients without MetS were
      enrolled as MetS-OA group and nMetS-OA group, respectively. VAS pain and WOMAC
      scores were higher in MetS-OA group compared with those in nMets-OA group (p <
      0.01). The leptin and free leptin levels in plasma and SF were significantly
      higher in MetS-OA group than those in nMetS-OA group, while the adiponectin
      levels were lower (All p < 0.01). Significant differences existed even after
      adjustment for body mass index (BMI) (p < 0.05). There were no significant
      associations between adipokines levels and the clinical severity of OA in MetS-OA
      group and nMetS-OA group respectively (p > 0.05). CONCLUSIONS: Leptin was higher
      and adiponectin was lower in knee osteoarthritis patients with MetS compared to
      those without MetS, independent of BMI. The higher SF and plasma levels of leptin
      in MetS-OA patients may need further studies to delineate their
      pathophysiological relationships.

PMID- 29335845
TI  - Carnosic Acid as a Promising Agent in Protecting Mitochondria of Brain Cells.
AB  - Carnosic acid (CA; C20H28O4), a phenolic diterpene characterized as an ortho
      dihydroquinone-type molecule, is a pro-electrophile agent that becomes an
      electrophile after reacting with free radicals. The electrophile generated from
      CA interacts with and activates the nuclear factor erythroid 2-related factor 2
      (Nrf2) transcription factor, which is a major modulator of redox biology in
      mammalian cells. CA induces antioxidant and anti-inflammatory effects in several
      cell types, as observed in both in vitro and in vivo experimental models. In this
      context, CA has been viewed as a neuroprotective agent by activating signaling
      pathways associated with cell survival during stressful conditions. Indeed, CA
      exhibits the ability to promote mitochondrial protection in neural cells.
      Mitochondria are the main source of both ATP and reactive species in animal
      cells. Mitochondrial dysfunction plays a central role in the start and
      development of neurodegenerative disorders, such as Alzheimer's disease,
      Parkinson's disease, and Huntington's disease, among others. Therefore, the study
      of strategies aiming to reduce mitochondrial impairment in the case of
      neurodegeneration is of pharmacological interest. In the present review, it is
      described and discussed the effects of CA on brain mitochondria in experimental
      models of neural lesion. Based on the data discussed here, CA is a potential
      candidate to be listed as a neuroprotective agent by acting on the mitochondria
      of neural cells.

PMID- 29335850
TI  - Functional outcome after endoscopic assisted release of the ulnar nerve for
      cubital tunnel syndrome: mid-to-long term results.
AB  - AIM OF THE STUDY: The aim of the study was to investigate functional and patient
      rated outcome parameters after endoscopic assisted release of the ulnar nerve for
      cubital tunnel syndrome. METHODS: One hundred of 204 consecutive patients between
      2006 and 2011 met the inclusion/exclusion criteria. Fifty-one of these patients
      were recruited and evaluated clinically and by questionnaire testing
      retrospectively after a mean follow-up of 82 months (range: 60-116). RESULTS:
      Neurological parameters (two-point-discrimination, application of Semmes
      Weinstein monofilaments, Tinel's test), grip, and three-point pinch strength were
      not significantly different from the contralateral extremity at the time of
      examination, whereas key pinch strength was significantly weaker. Mean
      Disabilities of the Arm, Shoulder, and Hand score was 20.82. Patients' overall
      opinion was good/excellent for 78% of the study population. DISCUSSION: The
      examined surgical procedure proved to be as efficacious as open in-situ
      decompression regarding functional outcome with fewer post-operative
      complications. Regarding the results it might be postulated that grip strength
      and three-point pinch strength determination is not necessarily relevant for
      ulnar nerve evaluation. CONCLUSION: Endoscopic assisted release of the ulnar
      nerve is a reliable and safe treatment option for cubital tunnel syndrome with
      satisfactory mid-to-long term functional and patient-rated outcomes.

PMID- 29335846
TI  - Cotinine: A Therapy for Memory Extinction in Post-traumatic Stress Disorder.
AB  - Post-traumatic stress disorder (PTSD) is a mental disorder that may develop after
      exposure to exceptionally threatening or unescapable horrifying events. Actual
      therapies fail to alleviate the emotional suffering and cognitive impairment
      associated with this disorder, mostly because they are ineffective in treating
      the failure to extinguish trauma memories in a great percentage of those
      affected. In this review, current behavioral, cellular, and molecular evidence
      supporting the use of cotinine for treating PTSD are reviewed. The role of the
      positive modulation by cotinine of the nicotinic acetylcholine receptors (nAChRs)
      and their downstream effectors, the protection of astroglia, and the inhibition
      of microglia in the PTSD brain are also discussed.

PMID- 29335851
TI  - The relation between personality, informal caregiving, life satisfaction and
      health-related quality of life: evidence of a longitudinal study.
AB  - PURPOSE: Personality characteristics of the caregiver might play a role in the
      relation between informal caregiving and health-related quality of life as well
      as life satisfaction. However, a limited body of research has examined this
      relation. This study aimed to examine the role personality characteristics of the
      caregiver might play in the relation between informal caregiving and well-being
      outcomes using a longitudinal approach. METHODS: Data were derived from the large
      Panel 'Labour Market and Social Security.' This is an annual household survey,
      which is conducted by order of the Institute for Employment Research covering
      persons and households registered as residents of Germany. The SF-12 was used to
      capture health-related quality of life (covering physical and mental health). A
      short version of the Big Five Inventory (BFI-K) was used to quantify personality
      factors. Life satisfaction was measured by a single-item measure. Concentrating
      on these factors, we used data from the third (2008/2009), sixth (2012), and
      ninth wave (2015). 34,548 observations were used in fixed effects regressions.
      RESULTS: Adjusting for various potential confounders, linear fixed effects
      regressions showed that the onset of informal caregiving reduced life
      satisfaction (beta = - .14, p < .01), but not physical and mental health. The
      relation between informal caregiving and life satisfaction was significantly
      moderated by agreeableness (p < .01). CONCLUSIONS: Findings of the present study
      emphasized that agreeableness moderates the relationship between informal
      caregiving and life satisfaction. Measuring personality characteristics of the
      informal caregiver is important for tailoring interventional strategies in order
      to increase the benefit of these programs.

PMID- 29335852
TI  - Authors' reply to "Rectal sparing approach after preoperative radio- and/or
      chemotherapy (RESARCH) in patients with rectal cancer: potential pitfalls of a
      multicentre observational study".

PMID- 29335853
TI  - Effect of nonwoven jute agrotextile mulch on soil health and productivity of
      broccoli (Brassica oleracea L.) in lateritic soil.
AB  - A field experiment was conducted in winter season of 2015-2016 in the dry
      lateritic soil of Eastern India to study the effect of different thicknesses of
      nonwoven jute agrotextile mulches (NJATM) along with other mulches on soil
      health, growth and productivity of broccoli (Brassica oleracea L.). The
      experiment was conducted in randomized block design with six treatments viz., T1
      (control, i.e. no mulching), T2 (300 gsm NJATM), T3 (350 gsm NJATM), T4 (400 gsm
      NJATM), T5 (rice straw) and T6 (black polythene mulch), each of which was
      replicated four times. The highest average curd weight (355.25 g) and yield (8.53
      t ha-1) of broccoli were recorded in T3 treatment. The lowest density of broad
      leaved weed, sedges and grasses were recorded in T6 treatment which was
      statistically at par with T4. All the treatments composing of NJATM increased the
      population of all the soil microbes except bacteria in the root rhizosphere of
      broccoli from their initial population. On average, the highest population of
      fungi (54.0 * 103 cfu per g) and actinomycetes (134.75 * 103 cfu per g) was
      recorded with T3 and T4 treatments respectively in the post-harvest soil. The
      soil moisture was conserved in all treatments compared to control showing highest
      moisture content in T4 treatment. Organic carbon and available N, P and K
      contents of soil were increased in all mulch treated plots compared to control,
      and their initial value and their highest value were recorded in T3. The NJATM of
      350 gsm thickness was very effective compared to other mulches in increasing the
      growth and productivity of broccoli by suppressing weeds, increasing moisture,
      microbial population and nutrient content of the lateritic soil.

PMID- 29335854
TI  - Nonreconstruction Options for Treating Medial Ulnar Collateral Ligament Injuries
      of the Elbow in Overhead Athletes.
AB  - PURPOSE OF REVIEW: This review aims to describe the nonreconstructive options for
      treating ulnar collateral ligament (UCL) injuries ranging from nonoperative
      measures, including physical therapy and biologic injections, to ligament repair
      with and without augmentation. RECENT FINDINGS: Nonoperative options for UCL
      injuries include guided physical therapy and biologic augmentation with platelet
      rich plasma (PRP). In some patients, repair of the UCL has shown promising return
      to sport rates by using modern suture and suture anchor techniques. Proximal
      avulsion injuries have shown the best results after repair. Currently, there is
      growing interest in augmentation of UCL repair with an internal brace. The
      treatment of UCL injuries involves complex decision making. UCL reconstruction
      remains the gold standard for attritional injuries and complete tears, which
      occur commonly in professional athletes. However, nonreconstructive options have
      shown promising results for simple avulsion or partial thickness UCL injuries.
      Future research comparing reconstructive versus nonreconstructive options is
      necessary.

PMID- 29335855
TI  - T cell responses to tumor: how dominant assumptions on immune activity led to a
      neglect of pathological functions, and how evolutionary considerations can help
      identify testable hypotheses for improving immunotherapy.
AB  - Cancer immunotherapy is based on the premise that activated, pro-inflammatory T
      cell responses to tumor will mostly combat tumor growth. Nowadays accepted as
      largely valid, this hypothesis has been formed as a result of extensive
      theoretical and experimental argumentation on the inherent function of the immune
      system and the nature of the immunological self, dating back to the foundations
      of immunology. These arguments have also been affected by how current working
      hypotheses were set by researchers, an issue that has been the focus of study by
      medical anthropologists. As a result of these processes, cancer immunotherapy has
      developed into a truly promising anti-cancer strategy, with very substantial
      benefits in clinical outcomes. However, as immunotherapy still has large margins
      for improvement, a more thorough examination of both the historical background
      and evolutionary context of current assumptions for how the immune system
      responds to cancer can help reveal novel, testable questions. We describe how
      attempting to answer some of these questions experimentally, such as identifying
      the contributors of tumor-associated fibrosis, has led to potentially useful
      insights on how to improve immunotherapy.

PMID- 29335856
TI  - Abscopal effects of radiotherapy and combined mRNA-based immunotherapy in a
      syngeneic, OVA-expressing thymoma mouse model.
AB  - BACKGROUND: Tumor metastasis and immune evasion present major challenges of
      cancer treatment. Radiotherapy can overcome immunosuppressive tumor
      microenvironments. Anecdotal reports suggest abscopal anti-tumor immune
      responses. This study assesses abscopal effects of radiotherapy in combination
      with mRNA-based cancer vaccination (RNActive(r)). METHODS: C57BL/6 mice were
      injected with ovalbumin-expressing thymoma cells into the right hind leg (primary
      tumor) and left flank (secondary tumor) with a delay of 4 days. Primary tumors
      were irradiated with 3 * 2 Gy, while secondary tumors were shielded. RNA and
      combined treatment groups received mRNA-based RNActive(r) vaccination. RESULTS:
      Radiotherapy and combined radioimmunotherapy significantly delayed primary tumor
      growth with a tumor control in 15 and 53% of mice, respectively. In small
      secondary tumors, radioimmunotherapy significantly slowed growth rate compared to
      vaccination (p = 0.002) and control groups (p = 0.01). Cytokine microarray
      analysis of secondary tumors showed changes in the cytokine microenvironment,
      even in the non-irradiated contralateral tumors after combination treatment.
      CONCLUSION: Combined irradiation and immunotherapy is able to induce abscopal
      responses, even with low, normofractionated radiation doses. Thus, the
      combination of mRNA-based vaccination with irradiation might be an effective
      regimen to induce systemic anti-tumor immunity.

PMID- 29335857
TI  - Effect of soothing Gan (Liver) and invigorating Pi (Spleen) recipes on TLR4-p38
      MAPK pathway in kupffer cells of non-alcoholic steatohepatitis rats.
AB  - OBJECTIVE: To investigate the mechanism of inflammatory-mediated toll-like
      receptor 4 (TLR4)-p38 mitogen-activated protein kinase (p38 MAPK) pathway in
      Kupffer cells (KCs) of non-alcoholic steatohepatitis (NASH) rats and the
      intervention effect of soothing Gan (Liver) and invigorating Pi (Spleen) recipes
      on this pathway. METHODS: After 1 week of acclimatization, 120 Sprague-Dawley
      male rats were randomly divided into 8 groups using a random number table (n=15
      per group): normal group, model group, low-dose Chaihu Shugan Powder (, CHSG)
      group (3.2 g/kg), high-dose CHSG group (9.6 g/kg), low-dose Shenling Baizhu
      Powder (, SLBZ) group (10 g/kg), high-dose SLBZ (30 g/kg) group, and low-and
      highdose integrated recipe (L-IR, H-IR) groups. All rats in the model and
      treatment groups were fed with a high-fat diet (HFD). The treatments were
      administrated by gastrogavage once daily and lasted for 26 weeks. The liver
      tissues were detected with hematoxylin-eosin (HE) and oil red O staining. Levels
      of liver lipids, serum lipids and transaminases were measured. KCs were isolated
      from the livers of rats to evaluate the mRNA expressions of TLR4 and p38 MAPK by
      real-time flfl uorescence quantitative polymerase chain reaction, and proteins
      expressions of TLR4, p-p38 MAPK and p38 MAPK by Western blot. Levels of
      inflammatory cytokines including tumor necrosis factor alpha (TNF-alpha),
      interleukin (IL)-1 and IL-6 in KCs were measured by enzyme-linked immunosorbent
      assay. RESULTS: After 26 weeks of HFD feeding, HE and oil red O staining showed
      that the NASH model rats successfully reproduced typical pathogenesis and
      histopathological features. Compared with the normal group, the model group
      exhibited signifificant increases in body weight, liver weight, liver index,
      serum levels of total cholesterol (TC), triglyceride (TG), low-density
      lipoprotein cholesterol, and aspartate aminotransferase as well as TC and TG
      levels in liver tissues, and significant decrease in serum level of high-density
      lipoprotein cholesterol (P<0.05 or P<0.01), while those indices were
      significantly ameliorated in the H-IR group (P<0.05 or P<0.01). Higher levels of
      TNF-alpha, IL-1 and IL-6 in KCs were observed in the model group compared with
      the normal group (P<0.01). Signifificant decreases in TNF-alpha, IL-1 and IL-6
      were observed in the H-SLBZ, H-IR and L-IR groups compared with the model group
      (P<0.05 or P<0.01). The mRNA expressions of TLR4 and p38 MAPK and protein
      expressions of TLR4, p38 MAPK and p-p38 MAPK in KCs in the model group were
      signifificantly higher than the normal group (P<0.01), while those expression
      levels in the L-IR and H-IR groups were signifificantly lower than the model
      group (P<0.05 or P<0.01). CONCLUSIONS: Inflfl ammation in KCs might play an
      important role in the pathogenesis of NASH in rats. The data demonstrated the
      importance of TLR4-p38MAPK signaling pathway in KCs for the anti-inflfl ammatory
      effect of soothing Gan and invigorating Pi recipes.

PMID- 29335858
TI  - Effects of Aidi injection () with Western medical therapies on quality of life
      for patients with primary liver cancer: a systematic review and meta-analysis.
AB  - OBJECTIVE: To evaluate the effects of Aidi Injection (, AD) in combination with
      Western medical therapies (WMT) in patients with primary liver cancer (PLC).
      METHODS: Randomized controlled trials (RCTs) comparing AD plus WMT with WMT alone
      were retrieved from inception to March 2013 by retrieving the literature database
      thoroughly and systematically. The extracted data from included studies were
      analyzed and synthesized by Review Manager 5.2 software. The Cochrane risk of
      bias tool was used to assess the quality of included studies, and Begg's and
      Egger's tests were used to evaluate the potential presence of publication bias.
      The studies were divided into 7 separate subgroups in terms of quality of life
      (QOL), recent chemotherapy and the incidence of leukocyte reduction. The subgroup
      analysis was applied to assess the heterogeneity between included researches, and
      the sensitivity analysis was used to weigh the stability of studies. RESULTS:
      Twenty-four RCTs were included in this study. Compared with WMT used alone, AD as
      additional intervention was more effective on improving QOL (P<0.01), increasing
      short-term effificacy (P<0.01), prolonging life (P<0.05 or P<0.01), relieving
      clinical symptoms (P<0.01), and reducing adverse events (e.g. reduce white blood
      cell counts, P=0.002; reduce in platelet counts, P<0.01). Subgroup analysis
      showed that the hepatic artery interventions with AD was superior in improving
      QOL (P<0.01) and enhancing short-term response rates (P=0.007) and reducing white
      blood cell counts (P=0.0004) than hepatic artery interventions alone (P<0.01).
      The chemoembolization plus AD or the chemotherapy plus AD were both better than
      chemoembolization or the chemotherapy alone in improving the QOL and short-term
      response rate (P<0.05 or P<0.01). CONCLUSIONS: AD in combination with WMT
      improves QOL in patients with PLC. Considering the inherent limitations of the
      included studies, further well-designed, rigorously performed, high-quality, and
      double-blinded RCTs with large sample sizes are needed.

PMID- 29335859
TI  - Arginine vasopressin-aquaporin-2 pathway-mediated dehydration effects of
      electroacupuncture in guinea pig model of AVP-induced endolymphatic hydrops.
AB  - OBJECTIVE: To investigate the effects of electroacupuncture (EA) on endolymphatic
      hydrops (EH) and the regulation of arginine vasopressin (AVP)-aquaporin-2 (AQP2)
      pathway in guinea pigs. METHODS: EH was induced in male guinea pigs by an
      intraperitoneal injection of AVP. For the treatment, EA was delivered to Baihui
      (GV 20) and Tinggong (SI 19) acupoints, once per day for 10 consecutive days. In
      histomorphological studies, cochlear hydrops degree was evaluated by hematoxylin
      eosin (HE) staining, and then the ratio of scala media (SM) area to SM + scala
      vestibuli (SV) area (R value) was calculated. In mechanical studies, a comparison
      of plasma AVP (p-AVP) concentrations, cyclic adenosine monophosphate (cAMP)
      levels, vasopressin type 2 receptor (V2R) and AQP2 mRNA expressions in the
      cochlea were compared among groups. RESULTS: EA significantly reduced cochlear
      hydrops in guinea pigs (P=0.001). EA significantly attenuated the AVPinduced up
      regulation of p-AVP concentrations (P=0.006), cochlear cAMP levels (P=0.003) and
      AQP2 mRNA expression (P=0.016), and up-regulated the expression of V2R mRNA
      (P=0.004) in the cochlea. CONCLUSIONS: The dehydrating effect of EA might be
      associated with its inhibition of AVP-AQP2 pathway activation.

PMID- 29335860
TI  - Effectiveness and safety of Chinese medicine for Idiopathic pulmonary fibrosis: A
      systematic review and meta-analysis.
AB  - OBJECTIVE: To evaluate the effectiveness and safety of Chinese medicine (CM) for
      Idiopathic pulmonary fifibrosis (IPF) patients. METHODS: To screened relevant
      articles, PubMed, Cochrane Library, Excerpta Medica Datase (EMBASE), China
      National Knowledge Infrastructure (CNKI), Chinese VIP Information (VIP), Wanfang
      Database and Chinese Biomedical Database (CBM) were searched in English or
      Chinese until December 2015 for randomized controlled trials, which compared CM
      treatment (CM group) with Western medicine or placebo (control group) on IPF. The
      outcome measures included acute exacerbation, pulmonary function, the St George's
      respiratory questionnaire (SGRQ) scores, 6-minute walk test (6MWT) distance,
      adverse events and mortality. RESULTS: This meta-analysis included 25 randomized
      controlled trials involving 1,471 patients. Compared with the control group, CM
      group was superiori in reducing the risk of exacerbation [relative risk
      (RR)=0.40, 95% CI 0.22 to 0.72, P<0.05], improving in forced expiratory volume in
      one second (FEV1) [standard mean difference (SMD)=0.62, 95% CI 0.40 to 0.84,
      P<0.01] and diffusion capacity for carbon monoxide (DLCO, SMD=0.40, 95% CI 0.22
      to 0.58, P<0.01), but there was no significant difference in vital capacity (VC,
      SMD=0.10, 95% CI-0.12 to 0.31, P>0.05). This meta-analysis also revealed that CM
      therapy signifificantly decreased the SGRQ score (SMD=-0.60, 95% CI-1.14 to-0.05,
      P<0.05) and improved 6MWT distance (SMD=0.59, 95% CI 0.34 to 0.84, P<0.01),
      compared with the control group. Meanwhile, CM therapy was associated with a low
      incidence of adverse effects (RR=0.19, 95% CI 0.08 to 0.43, P<0.01). However,
      there was no signifificant difference in mortality (RR=0.24, 95% CI 0.05 to 1.10,
      P>0.05) between CM and control groups. CONCLUSIONS: The pooled outcomes suggest
      that CM treatment appears benefifit in reducing the risk of exacerbation,
      improving lung function and decreasing the incidence of adverse effects and
      enhancing the quality of life. However, the outcomes were limited because of the
      low quality of the included studies. More rigorous clinic trials need to be
      carried out to provide suffificient and accurate evidence in the future.

PMID- 29335862
TI  - Rules of meridians and acupoints selection in treatment of Parkinson's disease
      based on data mining techniques.
AB  - OBJECTIVE: To help selecting appropriate meridians and acupoints in clinical
      practice and experimental study for Parkinson's disease (PD), the rules of
      meridians and acupoints selection of acupuncture and moxibustion were analyzed in
      domestic and foreign clinical treatment for PD based on data mining techniques.
      METHODS: Literature about PD treated by acupuncture and moxibustion in China and
      abroad was searched and selected from China National Knowledge Infrastructure and
      MEDLINE. Then the data from all eligible articles were extracted to establish the
      database of acupuncture-moxibustion for PD. The association rules of data mining
      techniques were used to analyze the rules of meridians and acupoints selection.
      RESULTS: Totally, 168 eligible articles were included and 184 acupoints were
      applied. The total frequency of acupoints application was 1,090 times. Those
      acupoints were mainly distributed in head and neck and extremities. Among all,
      Taichong (LR 3), Baihui (DU 20), Fengchi (GB 20), Hegu (LI 4) and Chorea-tremor
      Controlled Zone were the top five acupoints that had been used. Superior-inferior
      acupoints matching was utilized the most. As to involved meridians, Du Meridian,
      Dan (Gallbladder) Meridian, Dachang (Large Intestine) Meridian, and Gan (Liver)
      Meridian were the most popular meridians. CONCLUSIONS: The application of
      meridians and acupoints for PD treatment lay emphasis on the acupoints on the
      head, attach importance to extinguishing Gan wind, tonifying qi and blood, and
      nourishing sinews, and make good use of superior-inferior acupoints matching.

PMID- 29335863
TI  - Integrative medicine on optimizing clopidogrel and aspirin therapy.
AB  - This article reviews the available published data on optimizing clopidogrel and
      aspirin therapy using translational and integrative medicine. Translational and
      evidence-based medical studies show that the CYP2C19 gene mutation (CYP2C19*2 and
      CYP2C19*3) could affect > 50% of the Chinese population, and that this mutation
      is closely associated with clopidogrel resistance and an increased risk of major
      adverse cardiovascular events, particularly stent thrombosis in patients
      following percutaneous coronary intervention (PCI). Adjusted-dose warfarin and
      aspirin reduce stroke in patients with atrial fibrillation (AF), and warfarin is
      substantially more efficacious than aspirin. However, a poor compliance is a big
      problem in warfarin use especially in China. The genetic variants of vitamin K
      expoxide reductase might account for the universally lower warfarin dosage used
      in Chinese population. The available evidence indicates that the integrating
      mainstream treatments (e.g., clopidogrel, CYP2C19 genotyping) and non-mainstream
      medicines [e.g., Chinese medicines, Naoxintong Capsule (, NXT)] to treat CYP2C19
      gene mutation patients following PCI can be effective. Aspirin combined NXT and
      the adjusted-dose warfarin was equally effective in elderly patients with non
      valvular AF in prevention of ischemic stroke.

PMID- 29335861
TI  - Alterations of Gefitinib Pharmacokinetics by Co-administration of Herbal
      Medications in Rats.
AB  - OBJECTIVE: To evaluate the potential pharmacokinetic interactions of the
      anticancer agent gefitinib (Iressa(r)) and the oriental medications Guipi
      Decoction (, GPD, Guibi-tang in Korean) and Bawu Decoction (, BWD, Palmul-tang in
      Korean). METHODS: Methylcellulose (MC, control), GPD (1,200 mg/kg), or BWD (6,000
      mg/kg) was orally administered to rats either as a single dose or multiple doses
      prior to gefitinib administration. To examine the effects of a single dose of the
      herbal medicines, gefitinib (10 mg/kg) was orally administered after 5 min or 1 h
      of MC or the herbal medicine pretreatments. To examine the effects of the
      multiple doses of the herbal medicines, gefitinib (10 mg/kg) was orally
      administered following 7 consecutive days of the administration of MC or each
      herbal medicine. The plasma concentrations of gefitinib were determined with
      liquid chromatography-tandem mass spectrometry assay. The plasma concentration
      time profiles of gefitinib were analyzed with a noncompartmental analysis.
      RESULTS: Gefitinib was rapidly absorbed and showed a monoexponential decline with
      an elimination half-life of 3.7-4.1 h. The pharmacokinetics of gefitinib was not
      affected by GPD pretreatment. However, a significantly lower maximum plasma
      concentration (Cmax, P<0.05) and area under the curve (P<0.05), and a delayed
      time to reach Cmax (Tmax, P<0.01) were observed in both single- and multipledose
      BWD-pretreated rats compared with the control rats. CONCLUSIONS: BWD and not GPD
      might delay and interfere with gefitinib absorption. Further evaluations of the
      clinical significance of these findings are needed.

PMID- 29335864
TI  - Ethanol Extract of Lycopodium serratum Thunb. Attenuates Lipopolysaccharide
      Induced C6 Glioma Cells Migration via Matrix Metalloproteinase-9 Expression.
AB  - OBJECTIVE: To elucidate how ethanol extract of L. serratum (ELS) could exert anti
      migratory effects on glioma with the suppression of nuclear factor kappa B (NF
      kappaB) downstream pathway. METHODS: Cell viability of ELS on C6 glioma was
      detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)
      assay. Nitric oxide (NO) assay and 2',7'-dichlorofluorescin diacetate (DCFH-DA)
      assay were applied to measure NO production and reactive oxygen species (ROS)
      generation on lipopolysaccharide (LPS)-induced C6 glioma cells. NF-kappaB,
      mitogen-activated protein kinase (MAPK), inducible nictric oxide synthase (iNOS)
      and cyclooxygenase-2 (COX-2) protein were determined by Western blot. Wound
      healing assay was used to investigate the inhibitory effect of ELS on fetal
      bovine serum (FBS)-induced migration and matrix metalloproteinase (MMP)-9 and -2
      activity was examined by zymography. RESULTS: ELS suppressed LPS-induced
      phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal
      kinase (JNK), and p38 through inhibiting the expression of chemokine CCL2 (or
      monocyte chemoattractant protein-1, MCP-1). In addition, ELS inhibited the
      expression of iNOS, COX-2, and the production of NO by LPS in C6 glioma cells.
      ELS also significantly decreased serum-induced migration of C6 glioma cells in
      scratch wound healing in a dose-dependent manner (P<0.01). The activity of MMP-9
      and -2 were also significantly attenuated by ELS with LPS treatment (P<0.01).
      CONCLUSIONS: Our results suggest that downregulation of MMP-9 gene expression
      might be involved in the anti-migration effect of ELS against LPS-induced C6
      glioma cells.

PMID- 29335865
TI  - Beneficial Effect of Berberis amurensis Rupr. on Penile Erection.
AB  - OBJECTIVE: To investigate whether the methanol extract of Berberis amurensis
      Rupr. (BAR) augments penile erection using in vitro and in vivo experiments.
      METHODS: The ex vivo study used corpus cavernosum strips prepared from adult male
      New Zealand White rabbits. In in vivo studies for intracavernous pressure (ICP),
      blood pressure, mean arterial pressure (MAP), and increase of peak ICP were
      continuously monitored during electrical stimulation of Sprague-Dawley rats.
      RESULTS: Preconstricted with phenylephrine (PE) in isolated endotheliumintact
      rabbit corus cavernosum, BAR relaxed penile smooth muscle in a dose-dependent
      manner, which was inhibited by pretreatment with NG-nitro-L-arginine methyl ester
      (L-NAME), a nitric oxide synthase inhibitor, and 1H-[1,2,4]-oxadiazole-[4,3
      alpha]-quinoxalin-1-one, a soluble guanylyl cclase inhibitor. BAR significantly
      relaxed penile smooth muscles dose-dependently in ex vivo, and this was inhibited
      by pretreatment with L-NAME 1H-[1,2,4]-oxadiazole-[4,3-alpha]-quinoxalin-1-one.
      BAR-induced relaxation was significantly attenuated by pretreatment with
      tetraethylammonium (TEA, P<0.01), a nonselective K+ channel blocker, 4
      aminopyridine (4-AP, P<0.01), a voltage-dependent K+ channel blocker, and
      charybdotoxin (P<0.01), a large and intermediate conductance Ca2+ sensitive-K+
      channel blocker, respectively. BAR induced an increase in peak ICP, ICP/MAP ratio
      and area under the curve dose dependently. CONCLUSION: BAR augments penile
      erection via the nitric oxide/cyclic guanosine monophosphate system and Ca2+
      sensitive-K+ (BKCa and IKCa) channels in the corpus cavernosum.

PMID- 29335866
TI  - Balancing Effect of Biejiajian Oral Liquid () on ACE-Ang II-AT1R Axis and ACE2
      Ang-(1-7)-Mas Axis in Rats with CCl4-Induced Hepatic Fibrosis.
AB  - OBJECTIVE: To explore the effect of Biejiajian Oral Liquid (, BOL) on CCl4
      induced hepatic fibrosis in rats by detecting the changes in the levels of
      angiotensin II (Ang II), angiotensin-(1-7) [Ang-(1-7)], angiotensin-converting
      enzyme (ACE), ACE2, angiotensin II type 1 receptor (AT1R), Mas, etc. METHODS: A
      total of 180 Wistar rats were randomly divided into two groups by random digital
      table method: prevention experiment and treatment experiment. Each group was
      further subdivided into the following 6 subgroups: normal control group, model
      group, vitamin E [100 mg/(kg.d), VE] group, enalapril [10 mg/(kg.g), Ena] group,
      high-dosage [20 g/(kg.d)] BOL group, and low-dosage [10 g/(kg.d)] BOL group. The
      hepatic fibrosis rat model was established by subcutaneous injection of CCl4 for
      6 weeks. Prevention experiment and treatment experiment were administered with
      specific drugs at different times. At the end of treatment experiment, the
      pathological changes of liver were observed after hematoxylin-eosin staining. The
      expressions of ingredients in renin-angiotensin-aldosterone system (RAAS) such as
      AngII, Ang-(1-7), ACE, ACE2, AT1R, Mas, renin, CYP11B2 and angen in liver were
      detected by enzyme linked immunosorbent assay, immunohistochemistry method or
      reverse transcription-polymerase chain reaction, respectively. RESULTS: The
      levels of AngII and Ang-(1-7) at the 6th week increased by 496.10% and 73.64%,
      respectively, compared with those at the 2nd week in the model group (P<0.01).
      With prevention or treatment with high-dosage BOL, there was an evident reduction
      of AngII level but an improvement of Ang-(1-7) level. Specifically, AngII level
      of high-dosage group decreased by 77.50% in prevention experiment (P=0.000) and
      by 76.93% in treatment experiment (P=0.002) compared with that in the model
      group. Ang-(1-7) level increased by 91.69% in prevention experiment (P=0.006) and
      by 70.77% in the treatment experiment (P=0.010) compared with that in the model
      group. The expression levels of mRNA of renin, ACE, CYP11B2, angen and AT1R
      decreased by 58.15%, 99.90%, 99.84%, 99.99% and 99.99% (all P<0.01),
      respectively. CONCLUSIONS: BOL could help resist liver fibrosis in rats by
      enhancing the level of each ingredient in ACE2-Ang-(1-7)-Mas axis, while
      decreasing the level of each ingredient in ACE-AngII-AT1R axis. To some extent,
      BOL could enhance the regulation of RAAS in rats with CCl4-induced hepatic
      fibrosis.

PMID- 29335867
TI  - Can CT-based radiomics signature predict KRAS/NRAS/BRAF mutations in colorectal
      cancer?
AB  - OBJECTIVES: To investigate whether CT-based radiomics signature can predict
      KRAS/NRAS/BRAF mutations in colorectal cancer (CRC). METHODS: This retrospective
      study consisted of a primary cohort (n = 61) and a validation cohort (n = 56)
      with pathologically confirmed CRC. Patients underwent KRAS/NRAS/BRAF mutation
      tests and contrast-enhanced CT before treatment. A total of 346 radiomics
      features were extracted from portal venous-phase CT images of the entire primary
      tumour. Associations between the genetic mutations and clinical background,
      tumour staging, and histological differentiation were assessed using univariate
      analysis. RELIEFF and support vector machine methods were performed to select key
      features and build a radiomics signature. RESULTS: The radiomics signature was
      significantly associated with KRAS/NRAS/BRAF mutations (P < 0.001). The area
      under the curve, sensitivity, and specificity for predicting KRAS/NRAS/BRAF
      mutations were 0.869, 0.757, and 0.833 in the primary cohort, respectively, while
      they were 0.829, 0.686, and 0.857 in the validation cohort, respectively.
      Clinical background, tumour staging, and histological differentiation were not
      associated with KRAS/NRAS/BRAF mutations in both cohorts (P>0.05). CONCLUSIONS:
      The proposed CT-based radiomics signature is associated with KRAS/NRAS/BRAF
      mutations. CT may be useful for analysis of tumour genotype in CRC and thus
      helpful to determine therapeutic strategies. KEY POINTS: * Key features were
      extracted from CT images of the primary colorectal tumour. * The proposed
      radiomics signature was significantly associated with KRAS/NRAS/BRAF mutations. *
      In the primary cohort, the proposed radiomics signature predicted mutations. *
      Clinical background, tumour staging, and histological differentiation were unable
      to predict mutations.

PMID- 29335869
TI  - Magnetic resonance cholangiopancreatography with GRASE sequence at 3.0T: does it
      improve image quality and acquisition time as compared with 3D TSE?
AB  - OBJECTIVES: The current study evaluated the clinical usefulness of the gradient
      and spin-echo (GRASE) sequence with single breath-hold in 3.0 T magnetic
      resonance cholangiopancreatography (MRCP). We compared the acquisition time and
      image quality between GRASE and breath navigator-triggered 3D turbo spin echo (3D
      TSE). METHODS: We examined 54 consecutive patients who underwent MRCP with GRASE
      and 3D TSE. We compared the image acquisition time and contrast-to-noise ratio
      (CNR) between the common bile duct (CBD) and liver. Overall image quality,
      blurring, motion artifacts and CBD visibility were scored on a 4-point scale by
      two radiologists. Paired t-tests were used to compare the variables. RESULTS: The
      mean image acquisition time was 95 % shorter with the GRASE than with 3D TSE
      (GRASE: 20 s; 3D TSE: 6 min 27 s). The CNR of GRASE was significantly higher than
      that of 3D TSE (GRASE: 25.4 +/- 13.9 vs. 3D TSE: 18.2 +/- 9.6, p < 0.01). All
      qualitative scores for GRASE were significantly better than those for 3D TSE.
      CONCLUSIONS: 3.0 T MRCP with GRASE sequence with single breath-hold significantly
      improved the CNR of CBD with a 95 % shorter acquisition time compared with
      conventional 3D MRCP with 3D TSE. KEY POINTS: * MRCP acquisition time was 95%
      shorter with GRASE than with 3D TSE. * Overall image quality of GRASE was
      significantly better than 3D TSE. * Pancreaticobiliary tree visibility with GRASE
      was better than that with 3D TSE.

PMID- 29335868
TI  - Added value of ancillary imaging features for differentiating scirrhous
      hepatocellular carcinoma from intrahepatic cholangiocarcinoma on gadoxetic acid
      enhanced MR imaging.
AB  - OBJECTIVES: To determine ancillary features that help distinguish between
      scirrhous hepatocellular carcinoma (S-HCC) and intrahepatic cholangiocarcinoma
      (ICC) and investigate added value of ancillary features to enhancement pattern
      based diagnosis on gadoxetic acid-enhanced MRI. METHODS: This retrospective study
      included 96 patients with S-HCCs and 120 patients with ICCs who underwent
      gadoxetic acid MRI before surgical resection. Two observers reviewed MRIs of the
      tumours. After determining ancillary features for differentiating tumour types,
      we measured the diagnostic performance of adding ancillary features to
      enhancement pattern-based diagnosis. RESULTS: T2 central darkness, capsule and
      septum were significant and independent features differentiating S-HCC from ICC
      (p <= .06). Adding ancillary features to enhancement pattern led to increased
      accuracy (observer 1, 78.9 vs. 93.8 %; observer 2, 80.3 vs. 92.8 %; p < .001),
      sensitivity (observer 1, 74.5 vs. 96.4 %; observer 2, 77.1 vs. 93.2 %; p < .001
      and .001), and specificity (observer 1, 82.5 vs. 91.7 %; observer 2, 82.9 vs.
      92.5 %; p = .006 and .005) for diagnosis of S-HCC by differentiation from ICC.
      CONCLUSIONS: Adding ancillary features capsule, septum and T2 central darkness to
      conventional enhancement patterns on gadoxetic acid-enhanced MRI improved
      accuracy, sensitivity and specificity for S-HCC diagnosis with differentiation
      from ICC. KEY POINTS: * Capsule, septum, and T2 central darkness were ancillary
      features for S-HCC. * A typical HCC enhancement was seen in 31.3% of S-HCCs. *
      Ancillary MRI features were useful in differentiation between S-HCC and ICC.

PMID- 29335870
TI  - A New Species of Pararrhopalites Bonet & Tellez (Collembola, Symphypleona,
      Sminthuridae) from Iron Caves in Brazil.
AB  - A second species of the genus Pararrhopalites is described from caves inserted in
      iron ore lithology. Both species present a particular sensory organ in the
      interantennal region. The new species, Pararrhopalites ubiquum n.sp., has a wider
      distribution and it is not restricted to a single cave, as it is the case of
      Pararrhopalites sideroicus Zeppelini & Brito, in Fla Entomol 97(4):1733-1744,
      2014, being found even in the Mesovoid Shallow Substratum. An update to the
      previously published identification key is presented.

PMID- 29335871
TI  - Validation of tautomeric and protomeric binding modes by free energy
      calculations. A case study for the structure based optimization of D-amino acid
      oxidase inhibitors.
AB  - Optimization of fragment size D-amino acid oxidase (DAAO) inhibitors was
      investigated using a combination of computational and experimental methods.
      Retrospective free energy perturbation (FEP) calculations were performed for
      benzo[d]isoxazole derivatives, a series of known inhibitors with two potential
      binding modes derived from X-ray structures of other DAAO inhibitors. The good
      agreement between experimental and computed binding free energies in only one of
      the hypothesized binding modes strongly support this bioactive conformation.
      Then, a series of 1-H-indazol-3-ol derivatives formerly not described as DAAO
      inhibitors was investigated. Binding geometries could be reliably identified by
      structural similarity to benzo[d]isoxazole and other well characterized series
      and FEP calculations were performed for several tautomers of the deprotonated and
      protonated compounds since all these forms are potentially present owing to the
      experimental pKa values of representative compounds in the series. Deprotonated
      compounds are proposed to be the most important bound species owing to the
      significantly better agreement between their calculated and measured affinities
      compared to the protonated forms. FEP calculations were also used for the
      prediction of the affinities of compounds not previously tested as DAAO
      inhibitors and for a comparative structure-activity relationship study of the
      benzo[d]isoxazole and indazole series. Selected indazole derivatives were
      synthesized and their measured binding affinity towards DAAO was in good
      agreement with FEP predictions.

PMID- 29335872
TI  - Disruptor of telomeric silencing 1-like (DOT1L): disclosing a new class of non
      nucleoside inhibitors by means of ligand-based and structure-based approaches.
AB  - Chemical inhibition of chromatin-mediated signaling involved proteins is an
      established strategy to drive expression networks and alter disease progression.
      Protein methyltransferases are among the most studied proteins in epigenetics
      and, in particular, disruptor of telomeric silencing 1-like (DOT1L) lysine
      methyltransferase plays a key role in MLL-rearranged acute leukemia Selective
      inhibition of DOT1L is an established attractive strategy to breakdown aberrant
      H3K79 methylation and thus overexpression of leukemia genes, and leukemogenesis.
      Although numerous DOT1L inhibitors have been several structural data published no
      pronounced computational efforts have been yet reported. In these studies a first
      tentative of multi-stage and LB/SB combined approach is reported in order to
      maximize the use of available data. Using co-crystallized ligand/DOT1L complexes,
      predictive 3-D QSAR and COMBINE models were built through a python implementation
      of previously reported methodologies. The models, validated by either modeled or
      experimental external test sets, proved to have good predictive abilities. The
      application of these models to an internal library led to the selection of two
      unreported compounds that were found able to inhibit DOT1L at micromolar level.
      To the best of our knowledge this is the first report of quantitative LB and SB
      DOT1L inhibitors models and their application to disclose new potential
      epigenetic modulators.

PMID- 29335873
TI  - Agricultural non-point source pollution management in a reservoir watershed based
      on ecological network analysis of soil nitrogen cycling.
AB  - The Miyun Reservoir plays a pivotal role in providing drinking water for the city
      of Beijing. In this research, ecological network analysis and scenario analysis
      were integrated to explore soil nitrogen cycling of chestnut and Chinese pine
      forests in the upper basin of the Miyun Reservoir, as well as to seek favorable
      fertilization modes to reduce agricultural non-point source pollution. Ecological
      network analysis results showed that (1) the turnover time was 0.04 to 0.37 year
      in the NH4+ compartment and were 15.78 to 138.36 years in the organic N
      compartment; (2) the Finn cycling index and the ratio of indirect to direct flow
      were 0.73 and 11.92 for the chestnut forest model, respectively. Those of the
      Chinese pine forest model were 0.88 and 29.23, respectively; and (3) in the
      chestnut forest model, NO3- accounted for 96% of the total soil nitrogen loss,
      followed by plant N (2%), NH4+ (1%), and organic N (1%). In the Chinese pine
      forest, NH4+ accounted for 56% of the total soil nitrogen loss, followed by
      organic N (34%) and NO3- (10%). Fertilization mode was identified as the main
      factor affecting soil N export. To minimize NH4+ and NO3- outputs while
      maintaining the current plant yield (i.e., 7.85e0 kg N/year), a fertilization
      mode of 162.50 kg N/year offered by manure should be adopted. Whereas, to achieve
      a maximum plant yield (i.e., 3.35e1 kg N/year) while reducing NH4+ and NO3-
      outputs, a fertilization mode of 325.00 kg N/year offered by manure should be
      utilized. This research is of wide suitability to support agricultural non-point
      source pollution management at the watershed scale.

PMID- 29335874
TI  - Mass balance of arsenic fluxes in rivers impacted by gold mining activities in
      Paracatu (Minas Gerais State, Brazil).
AB  - Arsenic (As) is a dangerous and carcinogenic element and drinking water is its
      main pathway of human exposure. Gold mines are widely recognized as important
      sources of As pollution. This work proposes the assessment of As distribution
      along watersheds surrounding "Morro do Ouro" gold mine (Paracatu, southeastern
      Brazil). A balance approach between filtered As fluxes (As < 0.45 MUm) and
      suspended particulate material (AsSPM) in different river segments was applied.
      Ultrafiltration procedure was used to categorize As into the following classes:
      particulate > 0.1 MUm, colloidal < 0.1 MUm to > 10 kDa, dissolved < 10 kDa to > 1
      kDa, and truly dissolved < 1 kDa. By applying this approach, arsenic
      contributions from mining facilities were quantified in order to identify
      critical fluvial segments and support decision makers in actions of remediation.
      The mass balance indicated the occurrence of a decreasing gradient from upstream
      to downstream: (i) of the As concentrations higher than the limit established by
      Brazilian law (10 MUg L-1); (ii) of the ratio between specific fluxes (g As km-2
      day-1) and those determined using an uncontaminated watershed (a proxy for
      estimating the anthropic contribution), from 103 to 101; (iii) of the specific
      fluxes As < 0.45 MUm and AsSPM from 102 to 100; and (iv) of the negative balance
      output minus input for each river segment that suggests As accumulation in
      sediments along the rivers in both urban and rural areas, mainly due to SPM
      sedimentation and sorption by Fe oxyhydroxides. Ultrafiltration shattering showed
      concentrations of decreasing As with particle size; the SPM load (> 0.1 MUm) was
      almost one order higher to dissolved load (< 1 kDa).

PMID- 29335875
TI  - Seasonal variation and source apportionment of PM2.5-bound trace elements at a
      coastal area in southwestern Taiwan.
AB  - The aim of this study is to investigate the seasonal variations and source
      apportionment on atmospheric fine particulate matter (PM2.5) mass and associated
      trace element concentrations at a coastal area, in Chiayi County of southwestern
      Taiwan. Particle measurements were conducted in 2015. Twenty-three trace elements
      in PM2.5 were analyzed using inductively coupled plasma mass spectrometry (ICP
      MS). Multiple approaches of the enrichment factor (EF) analysis and positive
      matrix fraction (PMF) model were used to identify potential sources of PM2.5
      bound trace elements. Daily mean concentration of PM2.5 in cold season (25.41 MUg
      m-3) was higher than that in hot season (13.10 MUg m-3). The trace elements
      contributed 11.02 and 10.74% in total PM2.5 mass concentrations in cold season
      and hot season, respectively. The results of EF analysis confirmed that Sb, Mo,
      and Cd were the top three anthropogenic trace elements in the PM2.5; furthermore,
      carcinogenic elements (Cr, Ni, and As) and other trace elements (Na, K, V, Cu,
      Zn, Sr, Sn, Ba, and Pb) were attributable to anthropogenic emissions in both cold
      and hot seasons; however, highly enriched Li and Mn were observed only in cold
      season. The PMF model identified four main sources: iron and steel industry, soil
      and road dust, coal combustion, and traffic-related emission. Each of these
      sources has an annual mean contribution of 8.2, 27.5, 11.2, and 53.1%,
      respectively, to PM2.5. The relative dominance of each identified source varies
      with changing seasons. The highest contributions occurred in cold season for iron
      and steel industry (66.2%), in hot season for traffic-related emission (58.4%),
      soil and road dust (22.0%), and coal combustion (2.8%). These findings revealed
      that the PM2.5 mass concentration, PM2.5-bound trace element concentrations, and
      their contributions were various by seasons.

PMID- 29335876
TI  - Hydrogen metabolic patterns driven by Clostridium-Streptococcus community shifts
      in a continuous stirred tank reactor.
AB  - The hydrogen (H2) production efficiency in dark fermentation systems is strongly
      dependent on the occurrence of metabolic pathways derived from the selection of
      microbial species that either consume molecular H2 or outcompete hydrogenogenic
      bacteria for the organic substrate. In this study, the effect of organic loading
      rate (OLR) on the H2 production performance, the metabolic pathways, and the
      microbial community composition in a continuous system was evaluated. Two
      bacterial genera, Clostridium and Streptococcus, were dominant in the microbial
      community depending on the OLR applied. At low OLR (14.7-44.1 gLactose/L-d),
      Clostridium sp. was dominant and directed the system towards the acetate-butyrate
      fermentation pathway, with a maximum H2 yield of 2.14 molH2/molHexose obtained at
      29.4 gLactose/L-d. Under such conditions, the volumetric hydrogen production rate
      (VHPR) was between 3.2 and 11.6 LH2/L-d. In contrast, relatively high OLR (58.8
      and 88.2 gLactose/L-d) favored the dominance of Streptococcus sp. as co-dominant
      microorganism leading to lactate production. Under these conditions, the formate
      production was also stimulated serving as a strategy to dispose the surplus of
      reduced molecules (e.g., NADH2+), which theoretically consumed up to 5.72 LH2/L
      d. In such scenario, the VHPR was enhanced (13.7-14.5 LH2/L-d) but the H2 yield
      dropped to a minimum of 0.74 molH2/molHexose at OLR = 58.8 gLactose/L-d. Overall,
      this research brings clear evidence of the intrinsic occurrence of metabolic
      pathways detrimental for biohydrogen production, i.e., lactic acid fermentation
      and formate production, suggesting the use of low OLR as a strategy to control
      them.

PMID- 29335877
TI  - Development of cyclic AMP receptor protein-based artificial transcription factor
      for intensifying gene expression.
AB  - Vector-dependent gene overexpression typically relies on an efficient operon and
      sufficient RNA polymerases (RNAPs). The lac (lactose) operon is a paradigm of
      transcription control, and cyclic AMP receptor protein (CRP) is a global
      regulator capable of recruiting RNAPs. However, the gap between lac operon and
      CRP has not been well bridged. In this work, CRP was fused to lac repressor
      protein (lacI) to form an artificial transcription factor (ATF) with the
      expectation that when LacI acted on the lacO-positioned upstream of gene of
      interest, the LacI-tethered CRP would trap RNAPs and thus improve the expression
      of PuuC, an aldehyde dehydrogenase catalyzing 3-hydroxypropionaldehyde (3-HPA) to
      3-hydroxypropionic acid (3-HP) in Klebsiella pneumoniae. As expected, SDS-PAGE
      and HPLC showed enhanced PuuC expression and 3-HP production, respectively,
      compared to the control strain without expressing chimeric protein LacI-CRP.
      Moreover, quantitative real-time PCR demonstrated increased transcription levels
      of both PuuC and RNAP coding genes. In shake-flask cultivation, the recombinant
      K. pneumoniae strain coexpressing LacI-CRP and PuuC produced 1.67-fold of 3-HP
      relative to the stain only overexpressing PuuC. In bioreactor cultivation, the
      strain coexpressing LacI-CRP and PuuC produced 35.1 g/L 3-HP, whereas the strain
      without expressing LacI-CRP generated only 9.8 g/L 3-HP. Overall, these results
      indicated that as an ATF, LacI-CRP significantly boosted PuuC expression and 3-HP
      production. We envision that LacI-CRP as a plug-and-play part can be used for
      regulating gene expression.

PMID- 29335878
TI  - Antioxidant Compounds Recovery from Jucara Residue by Thermal Assisted
      Extraction.
AB  - This study aimed to recover bioactive compounds by solid-liquid extraction from
      the agro-industrial residue obtained during jucara fruits processing into pulp. A
      preliminary study using different solvents (methanol, ethanol and water)
      indicated ethanol in aqueous solution as the best solvent for antioxidants
      recovery. Then, a Box-Behnken design was applied considering as independent
      variables the solvent composition (30-70% ethanol in water), temperature (30-70 
      degrees C) and time (30-60 min), in order to evaluate the effects of these
      factors on antioxidant activity in jucara extract. Results showed that the
      extracts with higher antioxidant activity were obtained using 30% ethanol at 70 
      degrees C for 60 min; measurements included ABTS and DPPH assays, determination
      of total phenolic content and total monomeric anthocyanins. Furthermore, the
      effect of pH in antioxidants recovery was evaluated. For this purpose, the 30%
      ethanol solution was acidified to pH 1 and 2 with HCl. Principal component
      analysis showed the formation of three distinct groups: one characterized by high
      bioactive compounds content (pH 1.0), another with superior antioxidant activity
      (pH 5.75, non-acidified), and finally the group at pH 2 presenting the worst
      concentrations in the evaluated responses. HPLC analysis showed the presence of
      cyanidin-3-O-rutinoside and cyanidin-3-O-glucoside in the extracts. Therefore,
      the conventional solid-liquid extraction using renewable solvent can be
      successfully applied to recover bioactive compounds from jucara residue, which
      can be used by different food industries.

PMID- 29335879
TI  - Current Approaches and New Developments in the Pharmacological Management of
      Tourette Syndrome.
AB  - Tourette syndrome (TS) is a neurodevelopmental disorder of unknown etiology
      characterized by spontaneous, involuntary movements and vocalizations called
      tics. Once thought to be rare, TS affects 0.3-1% of the population. Tics can
      cause physical discomfort, emotional distress, social difficulties, and can
      interfere with education and desired activities. The pharmacologic treatment of
      TS is particularly challenging, as currently the genetics, neurophysiology, and
      neuropathology of this disorder are still largely unknown. However, clinical
      experience gained from treating TS has helped us better understand its
      pathogenesis and, as a result, derive treatment options. The strongest data exist
      for the antipsychotic agents, both typical and atypical, although their use is
      often limited in children and adolescents due to their side-effect profiles.
      There are agents in a variety of other pharmacologic categories that have
      evidence for the treatment of TS and whose side-effect profiles are more
      tolerable than the antipsychotics; these include clonidine, guanfacine, baclofen,
      topiramate, botulinum toxin A, tetrabenazine, and deutetrabenazine. A number of
      new agents are being developed and tested as potential treatments for TS. These
      include valbenazine, delta-9-tetrahydrocannabidiol, and ecopipam. Additionally,
      there are agents with insufficient data for efficacy, as well as agents that have
      been shown to be ineffective. Those without sufficient data for efficacy include
      clonazepam, ningdong granule, 5-ling granule, omega-3 fatty acids, and n
      acetylcysteine. The agents that have been shown to be ineffective include
      pramipexole and metoclopramide. We will review all of the established
      pharmacologic treatments, and discuss those presently in development.

PMID- 29335881
TI  - Reply to Reck-Burneo et al.: imaging anorectal and cloacal malformations.

PMID- 29335883
TI  - ?

PMID- 29335882
TI  - Clinical response to Vim's thalamic stereotactic radiosurgery for essential
      tremor is associated with distinctive functional connectivity patterns.
AB  - INTRODUCTION: Essential tremor (ET) is the most common movement disorder. Drug
      resistant ET can benefit from standard surgical stereotactic procedures (deep
      brain stimulation, thalamotomy) or minimally invasive high-intensity focused
      ultrasound (HIFU) or stereotactic radiosurgical thalamotomy (SRS-T). Resting
      state fMRI (rs-fMRI) is a non-invasive imaging method acquired in absence of a
      task. We examined whether rs-fMRI correlates with tremor score on the treated
      hand (TSTH) improvement 1 year after SRS-T. METHODS: We included 17 consecutive
      patients treated with left unilateral SRS-T in Marseille, France. Tremor score
      evaluation and rs-fMRI were acquired at baseline and 1 year after SRS-T. Resting
      state data (34 scans) were analyzed without a priori hypothesis, in Lausanne,
      Switzerland. Based on degree of improvement in TSTH, to consider SRS-T at least
      as effective as medication, we separated two groups: 1, <= 50% (n = 6, 35.3%); 2,
      > 50% (n = 11, 64.7%). They did not differ statistically by age (p = 0.86),
      duration of symptoms (p = 0.41), or lesion volume at 1 year (p = 0.06). RESULTS:
      We report TSTH improvement correlated with interconnectivity strength between
      salience network with the left claustrum and putamen, as well as between
      bilateral motor cortices, frontal eye fields and left cerebellum lobule VI with
      right visual association area (the former also with lesion volume). Longitudinal
      changes showed additional associations in interconnectivity strength between
      right dorsal attention network with ventro-lateral prefrontal cortex and a
      reminiscent salience network with fusiform gyrus. CONCLUSIONS: Brain connectivity
      measured by resting-state fMRI relates to clinical response after SRS-T. Relevant
      networks are visual, motor, and attention. Interconnectivity between visual and
      motor areas is a novel finding, revealing implication in movement sensory
      guidance.

PMID- 29335880
TI  - The long-term effect of erythropoiesis stimulating agents given to preterm
      infants: a proton magnetic resonance spectroscopy study on neurometabolites in
      early childhood.
AB  - BACKGROUND: Erythropoiesis stimulating agents (ESAs) are neuroprotective in cell
      and animal models of preterm birth. Prematurity has been shown to alter
      neurometabolite levels in children in studies using proton magnetic resonance
      spectroscopy (1H-MRS). OBJECTIVE: We hypothesized that ESA treatment in premature
      infants would tend to normalize neurometabolites by 4-6 years of age. MATERIALS
      AND METHODS: Children in a longitudinal study of neurodevelopment underwent MRI
      and 1H-MRS at approximately 4 years and 6 years of age. Prematurely born children
      (500-1,250 g birth weight) received ESAs (erythropoietin or darbepoetin) or
      placebo during their neonatal hospitalization, and these groups were compared to
      healthy term controls. 1H-MRS spectra were obtained from the anterior cingulate
      (gray matter) and frontal lobe white matter, assessing combined N-acetylaspartate
      and N-acetylaspartylglutamate (tNAA), myo-inositol, choline compounds (Cho),
      combined creatine and phosphocreatine, and combined glutamate and glutamine.
      RESULTS: No significant (P<=0.5) group differences were observed for any
      metabolite level. Significant age-related increases in white-matter tNAA and Cho
      were observed, as well as a trend for increased gray-matter tNAA. CONCLUSION:
      Neither prematurity nor neonatal ESA treatment was associated with differences in
      brain metabolite levels in the children of this study at a significance level of
      0.05. These findings suggest that earlier differences that might have existed had
      normalized by 4-6 years of age or were too small to be statistically significant
      in the current sample.

PMID- 29335884
TI  - Effects of moderate exercise on biochemical, morphological, and physiological
      parameters of the pancreas of female mice with estrogen deprivation and
      dyslipidemia.
AB  - Menopausal women are at high risk of developing heart disease. However, physical
      exercise practice can reverse this scenario. We evaluated the biochemical,
      morphological, and physiological effects of moderate aerobic physical exercise on
      the pancreas of knockout mice for LDL receptor with estrogen deprivation by
      ovariectomy. Animals were divided into six groups (n = 5): sedentary non
      ovariectomized control; sedentary ovariectomized control; trained ovariectomized
      control; sedentary non-ovariectomized LDL-R knockout; sedentary ovariectomized
      LDL-R knockout; and trained ovariectomized LDL-R knockout. Physical exercise
      practice promoted improvement in biometric and biochemical parameters analyzed,
      with reduction of visceral adipose tissue and VLDL, triglycerides, total
      cholesterol, and blood glucose levels. In addition, physical exercise practice
      altered the morphology of pancreatic islets and improved their response to the
      effects of menopause. Thus, physical exercise practice was fundamental to
      minimize the effects of dyslipidemia associated with ovariectomy in the
      pancreatic tissue of LDL-R knockout animals, contributing to reduce the risk of
      developing cardiac diseases in the menopause period.

PMID- 29335885
TI  - Glottic Foreign Body Removal: A Novel Approach.

PMID- 29335886
TI  - Effect of actual age on outcome at discharge in patients by surgical clipping and
      endovascular coiling for ruptured cerebral aneurysm in Japan.
AB  - The Japanese population features the highest rate of elderly individuals
      worldwide. However, the difference of actual age indication for surgical clipping
      (SC) and endovascular coiling (EC) has never reported. We clarified the effect of
      actual age on poor outcome at discharge in patients by each treatment for
      ruptured cerebral aneurysm according to the Japanese Stroke Data Bank. A total of
      3593 patients with ruptured saccular cerebral aneurysm were treated by SC and/or
      EC between 2000 and 2013. The effect of actual age on poor outcome (modified
      Rankin scale [mRS] score > 2) at discharge was evaluated by the cutoff age using
      receiver operating characteristic analysis for each treatment. There were 2666
      cases in the SC group and 881 cases in the EC group. The cutoff age for poor
      outcome was 3 to 9 years older for EC than for SC. The gap of cutoff age between
      two treatments was 3 years shorter in mild subarachnoid hemorrhage than severe
      cases. The gap of cutoff age between two treatments was 7 years in elderly
      patients over 65 years old. The cutoff age was 78 years old for both SC and EC in
      elderly female patients. In conclusion, the cutoff age for poor mRS score > 2 was
      3 to 9 years older for EC than for SC. Actual age was one of the indications for
      elderly patients to achieve the optimum outcome; however, the treatment
      indication should be carefully considered based on the condition in each country.

PMID- 29335887
TI  - Sphingadienes show therapeutic efficacy in neuroblastoma in vitro and in vivo by
      targeting the AKT signaling pathway.
AB  - Neuroblastoma is a childhood malignancy that accounts for approximately 15% of
      childhood cancer deaths. Only 20-35% of children with metastatic neuroblastoma
      survive with standard therapy. Identification of more effective therapies is
      essential to improving the outcome of children with high-stage disease.
      Sphingadienes (SD) are growth-inhibitory sphingolipids found in natural sources
      including soy. They exhibit chemopreventive activity in mouse models of colon
      cancer, where they mediate cytotoxicity by inhibiting key pro-carcinogenic
      signaling pathways. In this study, the effect of SD on neuroblastoma was
      analyzed. Low micromolar concentrations of SD were cytotoxic to transformed and
      primary neuroblastoma cells independently of N-Myc amplification status. SD
      induced both caspase-dependent apoptosis and autophagy in neuroblastoma cells.
      However, only inhibition of caspase-dependent apoptosis protected neuroblastoma
      cells from SD-mediated cytotoxicity. SD also inhibited AKT activation in
      neuroblastoma cells as shown by reduced phosphorylated AKT levels. Pre-treatment
      with insulin attenuated SD-mediated cytotoxicity in vitro. SD-loaded
      nanoparticles (NP) administered parenterally to immunodeficient mice carrying
      neuroblastoma xenografts resulted in cytotoxic levels of SD in the circulation
      and significantly reduced tumor growth compared to vehicle-treated controls.
      Analysis of tumor extracts demonstrated reduced AKT activation in tumors of mice
      treated with SD-NP compared to controls treated with empty NP. Our findings
      indicate SD are novel potential chemotherapeutic agents that promote
      neuroblastoma cell death and reduce tumorigenicity in vivo.

PMID- 29335888
TI  - Root lengthening with apical closure in two maxillary immature permanent central
      incisors after placement of mineral trioxide aggregate (MTA) as an apical plug.
AB  - BACKGROUND: Necrosis of permanent immature teeth is a common reason for
      consultation in paediatric dentistry. Apexification is a therapeutic procedure
      aiming to create an apical calcified barrier in open apex teeth. CASE REPORT: Two
      cases are presented in which apexification were completed on immature permanent
      traumatised incisors using a mineral trioxide aggregate (MTA) plug. FOLLOW-UP: At
      2 and 5 years showed apical closure and radicular elongation beyond the MTA plug.
      CONCLUSION: Unexpectedly, a regeneration of mineral tissues beyond the MTA plug
      occurred which is an uncommon outcome.

PMID- 29335890
TI  - Effectiveness of Sodium-Glucose Cotransporter-2 Inhibitor as an Add-on Drug to
      GLP-1 Receptor Agonists for Glycemic Control of a Patient with Prader-Willi
      Syndrome: A Case Report.
AB  - INTRODUCTION: Diabetes patients with Prader-Willi syndrome (PWS) are obese
      because of hyperphagia; weight control by dietary modification and medicine is
      required for glycemic control. There are several recent reports showing the
      effectiveness of GLP-1 receptor agonists (GLP-1RAs) for diabetes treatment in
      PWS. CASE REPORT: A 36-year-old Japanese male patient was diagnosed with PWS at
      10 years of age. At age 16 years, he was diagnosed with diabetes and began to
      take several kinds of oral hypoglycemic agents. At age 29 years, his BMI was 39.1
      kg/m2 and he was referred to our department for diabetes and obesity treatment.
      In the present case, the HbA1c was not improved by GLP-1RAs despite a 28-kg BW
      reduction, which included a 9-kg loss of muscle. Apprehensive of further loss of
      muscle mass, basal insulin of insulin glargine was administered in addition to
      GLP-1RAs. Immediately after the addition of tofogliflozin, a sodium-glucose
      cotransporter-2 (SGLT2) inhibitor, the patient's HbA1c decreased dramatically
      with only about an additional 3% BW reduction. We note an improvement in our case
      of lipid deposition in the pancreas confirmed by abdominal CT after the
      improvement of HbA1c. It is unknown whether this improvement of fatty pancreas
      was a cause or an effect of the improved glycemic control in the present case.
      CONCLUSION: This finding clearly supports the effectiveness of combining SGLT2
      inhibitors with GLP-1RAs for treatment of patients with PWS and non-alcoholic
      fatty pancreas disease.

PMID- 29335889
TI  - Comparison of gray matter volume between migraine and "strict-criteria" tension
      type headache.
AB  - BACKGROUND: Despite evidently distinct symptoms, tension-type headache (TTH) and
      migraine are highly comorbid and exhibit many similarities in clinical practice.
      The purpose of this study was to investigate whether both types of headaches are
      similar in brain morphology. METHODS: Consecutive patients with TTH and age- and
      sex-matched patients with migraine and healthy controls were enrolled for brain
      magnetic resonance imaging examination. Patients with TTH were excluded if they
      reported any headache features or associated symptoms of migraine. Changes in
      gray matter (GM) volume associated with headache diagnosis (TTH vs. migraine) and
      frequency (episodic vs. chronic) were examined using voxel-based morphometry. The
      correlation with headache profile and the discriminative ability between TTH and
      migraine were also investigated for these GM changes. RESULTS: In comparison with
      controls (n = 43), the patients with TTH (25 episodic and 24 chronic) exhibited a
      GM volume increase in the anterior cingulate cortex, supramarginal gyrus,
      temporal pole, lateral occipital cortex, and caudate. The patients with migraine
      (31 episodic and 25 chronic) conversely exhibited a GM volume decrease in the
      orbitofrontal cortex. These GM changes did not correlate with any headache
      profile. A voxel-wise 2 * 2 factorial analysis further revealed the substantial
      effects of headache types and frequency in the comparison of GM volume between
      TTH and migraine. Specifically, the migraine group (vs. TTH) had a GM decrease in
      the superior and middle frontal gyri, cerebellum, dorsal striatum, and precuneus.
      The chronic group (vs. episodic group) otherwise demonstrated a GM decrease in
      the bilateral insula and anterior cingulate cortex. In receiver operating
      characteristic analysis, the GM volumes of the left superior frontal gyrus and
      right cerebellum V combined had good discriminative ability for distinguishing
      TTH and migraine (area under the curve = 0.806). CONCLUSIONS: TTH and migraine
      are separate headache disorders with different characteristics in relation to GM
      changes. The major morphological difference between the two types of headaches is
      the relative GM decrease of the prefrontal and cerebellar regions in migraine,
      which may reflect a higher allostatic load associated with this disabling
      headache.

PMID- 29335891
TI  - Serum Bilirubin Concentration is Associated with Left Ventricular Remodeling in
      Patients with Type 2 Diabetes Mellitus: A Cohort Study.
AB  - INTRODUCTION: Previous studies have shown that serum bilirubin concentration is
      inversely associated with the risk of cardiovascular disease. The relationship
      between serum bilirubin concentration and left ventricular geometry, however, has
      not been investigated in patients with diabetes mellitus. METHODS: In this cohort
      study, 158 asymptomatic patients with type 2 diabetes mellitus without overt
      heart disease were enrolled. Left ventricular structure and function were
      assessed using echocardiography. Serum bilirubin concentration, glycemic control,
      lipid profile, and other clinical characteristics were evaluated, and their
      association with left ventricular geometry was determined. Patients with New York
      Heart Association Functional Classification greater than I, left ventricular
      ejection fraction less than 50%, history of coronary artery disease, severe
      valvulopathy, chronic atrial fibrillation, or creatinine clearance less than 30
      ml/min, and those receiving insulin treatment, were excluded. RESULTS: Univariate
      analyses showed that relative wall thickness (RWT) was significantly correlated
      with diastolic blood pressure (P = 0.003), HbA1c (P = 0.024), total cholesterol
      (P = 0.043), urinary albumin (P = 0.023), and serum bilirubin concentration (P =
      0.009). There was no association between left ventricular mass index and serum
      bilirubin concentration. Multivariate linear regression analysis showed that log
      RWT was positively correlated with diastolic blood pressure (P = 0.010) and that
      log RWT was inversely correlated with log bilirubin (P = 0.003). In addition, the
      patients with bilirubin less than 0.8 mg/dl had a higher prevalence of concentric
      left ventricular remodeling compared with those with bilirubin 0.8 mg/dl or more.
      CONCLUSION: Our study shows that the serum bilirubin concentration may be
      associated with the progression of concentric left ventricular remodeling in
      patients with type 2 diabetes mellitus.

PMID- 29335892
TI  - Is sugammadex alone sufficient to cause anaphylaxis?

PMID- 29335893
TI  - Neurological prognosis of 6 cases after chest compression during general
      anesthesia.
AB  - INTRODUCTION: Data on the outcomes after chest compression (CC) of patients who
      are under general anesthesia (GA) are limited. The present study aimed to
      evaluate the neurological outcomes in patients who received CC while under GA.
      METHODS: The patients who received CC while under GA, between 2010 and 2015, in
      Kyoto Medical Center were surveyed retrospectively. The primary outcome was poor
      neurologic function or death, as defined by a cerebral performance category score
      (CPC) score of 3-5 on day 28. RESULTS: Six patients received CC while under GA,
      and four patients had poor neurological outcomes with a CPC score of 4 or 5 on
      day 28. All these patients required emergency operation because of their primary
      disease. CONCLUSION: Even if the patients were monitored and immediately managed
      under GA, ineffective management of preoperative conditions tended to result in
      the poor neurological prognosis.

PMID- 29335894
TI  - Management of periprosthetic shoulder infections with the use of a permanent
      articulating antibiotic spacer.
AB  - INTRODUCTION: Management of periprosthetic shoulder infections (PSIs) still
      remains challenging. We conducted a retrospective case study to assess the
      outcomes of definitive articulating antibiotic spacer implantation in a cohort of
      elderly, low-demanding patients. We hypothesized that in patients with low
      functional demands seeking pain relief with chronic PSIs, treatment with a
      definitive articulating antibiotic spacer would lead to satisfying results
      concerning eradication of the infection, improvement of pain, and improving
      shoulder function. MATERIALS AND METHODS: 19 patients underwent definitive
      articulating antibiotic spacer implantation for the treatment of an infected
      shoulder arthroplasty. Mean age at surgery was 70.2 years. Patients were assessed
      pre-operatively with functional assessment including Constant-Murley score, and
      objective examination comprehending ROM, visual analog scale pain score, and
      patient subjective satisfaction (excellent, good, satisfied, or unsatisfied)
      score. Radiographs were taken to examine signs of loosening, and change in
      implant positioning. RESULTS: At the most recent follow-up, none of the patients
      had clinical or radiographic signs suggesting recurrent infection. Most patients
      reported satisfying subjective and objective outcomes. Follow-up examination
      showed significant improvement of all variables compared to pre-operative values
      (p < 0.001). Radiographs did not show progressive radiolucent lines or change in
      the position of the functional spacer. In one case, glenoid osteolysis was
      reported, which did not affect the clinical outcome. CONCLUSIONS: In selected
      elderly patients with low functional demands seeking pain relief with infected
      shoulder arthroplasty, definitive management with a cement spacer is a viable
      treatment option that helps in eradicating shoulder infection and brings
      satisfying subjective and objective outcomes. LEVEL OF EVIDENCE: Case series,
      Level IV.

PMID- 29335895
TI  - Pharmacokinetics, Antiviral Activity, and Safety of Rilpivirine in Pregnant Women
      with HIV-1 Infection: Results of a Phase 3b, Multicenter, Open-Label Study.
AB  - INTRODUCTION: Physiologic changes during pregnancy may impact the
      pharmacokinetics of drugs. In addition, efficacy and safety/tolerability concerns
      have been identified for some antiretroviral agents. METHODS: Human
      immunodeficiency virus (HIV)-1-infected pregnant women (18-26 weeks gestation)
      receiving the non-nucleoside reverse transcriptase inhibitor rilpivirine 25 mg
      once daily were enrolled in this phase 3b, open-label study examining the impact
      of pregnancy on the pharmacokinetics of rilpivirine when it is given in
      combination with other antiretroviral agents. Blood samples (collected over the
      24-h dosing interval) to assess total and unbound rilpivirine plasma
      concentrations were obtained during the second and third trimesters (24-28 and 34
      38 weeks gestation, respectively) and 6-12 weeks postpartum. Pharmacokinetic
      parameters were derived using noncompartmental analysis and compared (pregnancy
      versus postpartum) using linear mixed effects modeling. Antiviral and immunologic
      response and safety were assessed. RESULTS: Nineteen women were enrolled; 15 had
      evaluable pharmacokinetic results. Total rilpivirine exposure was 29-31% lower
      during pregnancy versus postpartum; differences were less pronounced for unbound
      (pharmacodynamically active) rilpivirine. At study entry, 12/19 (63.2%) women
      were virologically suppressed; 10/12 (83.3%) women were suppressed at the
      postpartum visit. Twelve infants were born to the 12 women who completed the
      study (7 discontinued); no perinatal viral transmission was observed among 10
      infants with available data. Rilpivirine was generally safe and well tolerated in
      women and infants exposed in utero. CONCLUSION: Despite decreased rilpivirine
      exposure during pregnancy, treatment was effective in preventing mother-to-child
      transmission and suppressing HIV-1 RNA in pregnant women. Results suggest that
      rilpivirine 25 mg once daily, as part of individualized combination
      antiretroviral therapy, may be an appropriate option for HIV-1-infected pregnant
      women. TRIAL REGISTRATION: ClinicalTrials.gov Identifier, NCT00855335.

PMID- 29335896
TI  - Familial occurrence of gastroschisis: a population-based overview on recurrence
      risk, sex-dependent influence, and geographical distribution.
AB  - PURPOSE: There is uncertainty over whether familial recurrences in gastroschisis
      might be higher. Moreover, scant information is available regarding its
      sociodemographic features. We aim to explore the recurrence risk, sex-dependent
      influence, and geographical distribution of familial gastroschisis. METHODS: A
      systematic review of the literature and data extraction from population-based
      studies published 1970-2017 (PubMed/MEDLINE) was independently performed by two
      reviewers. Familial ocurrence of gastroschisis, whereas sociodemographic features
      from 11 studies were pooled including 862 probands as a base. A descriptive
      analysis and Chi-square test were performed. RESULTS: Twenty-four probands had a
      positive family history of gastroschisis including 49 affected family members,
      for a recurrence risk of 5.7 and 3% adjusted for proband. Siblings' recurrence
      was 4.3%. Sex-dependent influence analysis (n = 879, from three studies)
      evidenced an increased susceptibility to gastroschisis in males (2.5%) compared
      to females (1.3%) adjusted for proband. Heterogeneity was identified by Fisher's
      exact test (P = 0.023). CONCLUSION: Our findings support a greater liability
      attributable to familial factors on gastroschisis along with significant
      information for family and prenatal counseling. We suggest that future studies
      should include for a more accurate account for both familial and environmental
      confounding factors to uncover relatives and environmental exposures that more
      limited family histories may have missed.

PMID- 29335897
TI  - Splenectomy in systemic lupus erythematosus and autoimmune hematologic disease: a
      comparative analysis.
AB  - : The objective of the study is to analyze the efficacy and safety of splenectomy
      in the management of refractory autoimmune thrombocytopenia (AT)/autoimmune
      hemolytic anemia (AIHA) associated or not with systemic lupus erythematosus.
      Thirty-four patients after splenectomy due to severe AT and/or AIHA were divided
      into group 1 (G1) 18 SLE/APS patients: 9 AT/SLE patients, 6 SLE/antiphospholipid
      syndrome (APS), and 3 primary APS. Group 2 (G2): 16 patients without SLE/APS: 2
      Fisher-Evans syndrome and 14 AIHA. Surgery approach when (1) platelets <=
      50,000/ml despite 2 weeks on medical therapy, (2) medically dependent, and (3)
      medically intolerant or after two hemolytic crises in AIHA patients. Splenectomy
      response: (1) complete (CR): >= 150,000 platelets/ml, (2) partial: 50,000
      149,000/ml, or (3) none: <= 50,000/ml. CR for AIHA: hemoglobin >=9 g/dl.
      STATISTICAL ANALYSIS: descriptive statistics and chi-square test. The mean age
      was 34.6 years; mean follow-up: 28.5 months. Open splenectomy in 15/34 vs
      laparoscopy in 19/34 (p = NS). CR in 15/34, G1: 4/18, G2: 11/16, (p = 0.006).
      Complications in 6/34, 5 from G2 vs 1 from G1 (p = 0.05). Relapse in 7/18
      patients in G1 and 3/16 in G2 (p = 0.05). Open and laparoscopic splenectomies in
      SLE and AT patients are as effective as in those without SLE; however, patients
      with SLE and APS had more relapses.

PMID- 29335898
TI  - The novel transcription factor TRP interacts with ZFP5, a trichome initiation
      related transcription factor, and negatively regulates trichome initiation
      through gibberellic acid signaling.
AB  - KEY MESSAGE: The trichome-related protein (TRP) is a novel transcription factor
      (TF) that negatively regulates trichome initiation-related TFs through
      gibberellin (GA) signaling. Trichomes, which are outgrowths of leaf epidermal
      cells, provide the plant with a first line of defense against damage from
      herbivores and reduce transpiration. The initiation and development of trichomes
      are regulated by a network of positively or negatively regulating transcription
      factors (TFs). However, little information is currently available on
      transcriptional regulation related to trichome formation. Here, we report a novel
      TF Trichome-Related Protein (TRP) that was observed to negatively regulate the
      trichome initiation-related TFs through gibberellic acid (GA) signaling.
      ProTRP:GUS revealed that TRP was only expressed in the trichome. The TRP loss-of
      function mutant (trp) had an increased number of trichomes on the flower, cauline
      leaves, and main inflorescence stems compared to the wild-type. In contrast, TRP
      overexpression lines (TRP-Ox) exhibited a decreased number of trichomes on
      cauline leaves and main inflorescence stem following treatment with exogenous GA.
      Moreover, the expressions of trichome initiation regulators (GIS, GIS2, ZFP8,
      GL1, and GL3) increased in trp plants but decreased in TRP-Ox lines after GA
      treatment. TRP was observed to physically interact with ZFP5, a C2H2 TF that
      controls trichome cell development through GA signaling, both in vivo and in
      vitro. Based on these results, we suggest that TRP functions upstream of the
      trichome initiation regulators and represses the binding of ZFP5 to the ZFP8
      promoter.

PMID- 29335899
TI  - The ultrasonographic "whirlpool sign" in testicular torsion: valuable tool or
      waste of valuable time? A systematic review and meta-analysis.
AB  - PURPOSE: A positive whirlpool sign (WS) is defined as the presence of a spiral
      like pattern when the spermatic cord is assessed during ultrasonography (US),
      using standard, high-resolution ultrasonography (HRUS) and/or color Doppler
      sonography (CDS), in the presence of testicular torsion. The objective of this
      review was to assess the validity and accuracy of this sign by performing a
      comprehensive systematic literature review and meta-analysis. METHODS: In
      accordance with the Preferred Reporting Items for Systematic Reviews and Meta
      analyses (PRISMA) guidelines, a comprehensive literature search was performed
      (August, 2017), using the following databases: BMJ Best Practice, Cochrane
      Library, Embase, PubMed, Scopus, and Web of Science. Selected studies were
      further assessed for relevance and quality using the Oxford 2010 Critical
      Appraisal Skills Program (CASP). RESULTS: Of the studies assessed, a total of 723
      participants were included, with a mean of 72.3 (SD 71.9) participants. Of the
      participants, 226 (31.3%) were diagnosed with testicular torsion (TT). Meta
      analysis of the studies that provided sufficient data resulted in a pooled
      sensitivity and specificity of the WS of 0.73 (95% CI, 0.65-0.79) and 0.99 (95%
      CI, 0.92-0.99), respectively. Removal of all neonates increased the pooled
      sensitivity to 0.92 (95% CI, 0.70-0.98) while the pooled specificity remained
      almost unchanged at 0.99 (95% CI, 0.95-1.00). The estimated summary effect of all
      studies with sufficient data was 4.34 (95% CI, 1.01-7.67; n = 394; p = 0.001). A
      large degree of heterogeneity was suggested by an I2 statistic of 88.27% (95% CI,
      68.60-98.68%). Removal of neonatal subjects increased the estimated summary
      effect to 5.32 (95% CI, 1.59-9.05; n = 375; p = 0.001). CONCLUSION: The WS, when
      correctly diagnosed, may be viewed as a very definitive sign for TT in the
      pediatric and adult populations. However, its role in neonates is limited.

PMID- 29335900
TI  - Hypercomplex pedicle subtraction osteotomies: definition, early clinical and
      radiological results and complications.
AB  - PURPOSE: To describe hypercomplex pedicle subtraction osteotomies (HyC-PSO) for
      adult spine deformity with sagittal imbalance in terms of preoperative,
      intraoperative and postoperative outcomes and complications. METHODS: From a
      prospective single centre database, patients undergoing PSO between January 2016
      and May 2017 were reviewed. HyC-PSO were defined as those in patients with one of
      the following conditions: sagittal correction > 45 degrees  needed at a single
      level or at 1-3 consecutive vertebrae, more than 60 degrees  of total sagittal
      correction needed and PSO on segments of the spine with congenital deformities.
      RESULTS: 22 patients were included, 14 had standard PSO (group A) and 8 had HyC
      PSO (group B). Significant correction of lumbar lordosis (LL) and pelvic (PT) was
      noted in both groups (p < 0.01). Operative time was longer in HyC-PSO, 604 min
      compared to standard PSO, 478 min. A trend versus greater intraoperative blood
      loss (3837 vs 2285 ml) and greater intraoperative blood infusion (from cell saver
      plus homologous, 2306 vs 1280 ml) was recorded in HyC-PSO (ns). Patients in group
      B received significantly more blood units intra and postoperatively (8.25 vs 4.71
      units, p = 0.006). Sagittal correction at the PSO level (54.7 degrees -30 degrees
      to 85 degrees -vs 26.8 degrees -8 degrees  to 39 degrees -, p = 0.000) and total
      sagittal correction (64.5 degrees -50 to 95 degrees -vs 39.8 degrees -20 degrees 
      to 51 degrees -, p = 0.000) were greater in HyC-PSO. PROMs at the last available
      follow-up did not show significant differences between groups for any of the
      outcomes analyzed. Complications were similar in both groups. CONCLUSION: This is
      the first report on hypercomplex pedicle subtraction osteotomies. Hypercomplex
      PSO describes a subset of clinical scenarios with increased surgical effort that
      can be measured as longer surgical time and greater blood transfusion
      requirements. Successful correction of misalignment can be achieved in this
      specific group of patients, and clinical results and complications profile could
      be similar to standard PSO procedures.

PMID- 29335901
TI  - Letter to the Editor concerning "Spinal movement and dural sac compression during
      airway management in a cadaveric model with atlanto-occipital instability" by
      Liao S, Schneider NRE, Weilbacher F, et al. (2017) Eur Spine J;
      doi:10.1007/s00586-017-5416-9.

PMID- 29335902
TI  - Letter to the Editor concerning "Clinical and radiological factors related to the
      presence of motor deficit in lumbar disc prolapse: a prospective analysis of 70
      consecutive cases with neurological deficit" by V. Krishnan et al. [Eur Spine J
      (2017) 26:2642-2649).

PMID- 29335903
TI  - Anterior cervical corpectomy and fusion versus posterior laminoplasty for the
      treatment of oppressive myelopathy owing to cervical ossification of posterior
      longitudinal ligament: a meta-analysis.
AB  - PURPOSE: The purpose of this research is to compare the clinical efficacy,
      postoperative complication and surgical trauma between anterior cervical
      corpectomy and fusion versus posterior laminoplasty for the treatment of
      oppressive myelopathy owing to cervical ossification of the posterior
      longitudinal ligament (OPLL). STUDY DESIGN: Systematic review and meta-analysis.
      METHODS: An comprehensive search of literature was implemented in three
      electronic databases (Embase, Pubmed, and the Cochrane library). Randomized or
      non-randomized controlled studies published since January 1990 to July 2017 that
      compared anterior cervical corpectomy and fusion (ACCF) versus posterior
      laminoplasty (LAMP) for the treatment of cervical oppressive myelopathy owing to
      OPLL were acquired. Exclusion criteria were non-human studies, non-controlled
      studies, combined anterior and posterior operative approach, the other anterior
      or posterior approaches involving cervical discectomy and fusion and laminectomy
      with (or without) instrumented fusion, revision surgeries, and cervical
      myelopathy caused by cervical spondylotic myelopathy. The quality of the included
      articles was evaluated according to GRADE. The main outcome measures included:
      preoperative and postoperative Japanese Orthopedic Association (JOA) score; neuro
      functional recovery rate; complication rate; reoperation rate; preoperative and
      postoperative C2-C7 Cobb angle; operation time and intraoperative blood loss; and
      subgroup analysis was performed according to the mean preoperative canal
      occupying ratio (Subgroup A:the mean preoperative canal occupying ratio < 60%,
      and Subgroup B:the mean preoperative canal occupying ratio >= 60%). RESULTS: A
      total of 10 studies containing 735 patients were included in this meta-analysis.
      And all of the selected studies were non-randomized controlled trials with
      relatively low quality as assessed by GRADE. The results revealed that there was
      no obvious statistical difference in preoperative JOA score between the ACCF and
      LAMP groups in both subgroups. Also, in subgroup A (the mean preoperative canal
      occupying ratio < 60%), no obvious statistical difference was observed in the
      postoperative JOA score and neurofunctional recovery rate between the ACCF and
      LAMP groups. But, in subgroup B (the mean preoperative canal occupying ratio >=
      60%), the ACCF group illustrated obviously higher postoperative JOA score and
      neurofunctional recovery rate than the LAMP group (P < 0.01, WMD 1.89 [1.50,
      2.28] and P < 0.01, WMD 24.40 [20.10, 28.70], respectively). Moreover, the
      incidence of both complication and reoperation was markedly higher in the ACCF
      group compared with LAMP group (P < 0.05, OR 1.76 [1.05, 2.97] and P < 0.05, OR
      4.63 [1.86, 11.52], respectively). In addition, the preoperative cervical C2-C7
      Cobb angle was obviously larger in the LAMP group compared with ACCF group (P <
      0.05, WMD - 5.77 [- 9.70, - 1.84]). But no statistically obvious difference was
      detected in the postoperative cervical C2-C7 Cobb angle between the two groups.
      Furthermore, the ACCF group showed significantly more operation time as well as
      blood loss compared with LAMP group (P < 0.01, WMD 111.43 [40.32,182.54], and P <
      0.01, WMD 111.32 [61.22, 161.42], respectively). CONCLUSION: In summary, when the
      preoperative canal occupying ratio < 60%, no palpable difference was tested in
      postoperative JOA score and neurofunctional recovery rate. But, when the
      preoperative canal occupying ratio >= 60% ACCF was associated with better
      postoperative JOA score and the recovery rate of neurological function compared
      with LAMP. Synchronously, ACCF in the cure for cervical myelopathy owing to OPLL
      led to more surgical trauma and more incidence of complication and reoperation.
      On the other hand, LAMP had gone a diminished postoperative C2-C7 Cobb angle,
      that might be a cause of relatively higher incidence of postoperative late
      neurofunctional deterioration. In brief, when the preoperative canal occupying
      ratio < 60%, LAMP seems to be effective and safe. However, when the preoperative
      canal occupying ratio >= 60%, we prefer to choose ACCF while complications could
      be controlled by careful manipulation and advanced surgical techniques. No matter
      which option you choose, benefits and risks ought to be balanced.

PMID- 29335904
TI  - The SAFE pathway for cardioprotection: is this a promising target?
AB  - The survivor activating factor enhancement (SAFE) pathway was discovered as an
      alternative intrinsic pro-survival signaling pathway to the reperfusion injury
      salvage kinase pathway for cardioprotection against ischemia-reperfusion injury.
      The delineation of this pathway, made of key components such as cytokines of the
      immune system and transcription factors, has brought major advancements in our
      understanding on how the heart is able to protect itself against ischemia
      reperfusion injury. In this viewpoint, we describe the major steps leading to the
      discovery of the SAFE pathway in small animal models to date and we discuss its
      translation to large animals and humans.

PMID- 29335905
TI  - Influence of antiviral therapy on the liver stiffness in chronic HBV hepatitis.
AB  - PURPOSE: The aim of this study was to evaluate the effects of antiviral therapy
      on liver stiffness measurement (LSM). METHODS: Two hundred HBV patients were
      enrolled from four hospital centers in southern Italy; median age was 50.7 (25
      75) males were 68%; 171 patients underwent to liver biopsy and 200 patients had
      LSM at baseline and 189 at the end of follow-up. One hundred and forty-nine
      patients were treated with nucleos(t)ide analogs, while 51 patients were
      untreated. The cutoffs of the LSM, related to the fibrosis stages, were as
      follows: non-advanced fibrosis <= 8.1 kPa and advanced fibrosis >= 8.2 Kpa.
      RESULTS: At baseline, the median value of LSM was 14.1 kPa for advanced
      fibrosis/cirrhosis and 6.9 kPa for non-advanced fibrosis. LSM was performed at 24
      months from the start of therapy. The treated patients (68% received Entecavir
      and 32% Tenofovir) showed a decrease in liver stiffness measurement of 1.5 kPa (p
      < 0.001) in non-advanced fibrosis and of 6 kPa (p < 0.001) in advanced
      fibrosis/cirrhosis. In the patients not undergoing antiviral treatment, no
      statistically significant change of the LSM was observed (p = 0.26). A logistic
      binary regression model showed that the only independent factor associated with a
      significant change in the LSM was the liver stiffness value at baseline (odd
      ratio 2.855; 95% CI 1.456-5.788; (p = 0.007). CONCLUSION: Long-term antiviral
      therapy induced a significant reduction of liver stiffness measurement and this
      result may be related to the reduction of liver fibrosis.

PMID- 29335906
TI  - The Health Behaviors of Ethnically Diverse Women at Increased Risk of Gestational
      Diabetes: The Behaviors Affecting Baby and You (B.A.B.Y.) Study.
AB  - Objectives Cigarette smoking, low physical activity, and sedentary behavior are
      modifiable risk factors for adverse pregnancy outcomes. However, only one study
      has evaluated predictors of these health risk behaviors among women at high risk
      for gestational diabetes mellitus (GDM). Therefore, our goal was to examine
      predictors of smoking, low physical activity, and sedentary behavior during
      pregnancy in an ethnically diverse high risk cohort. Methods This cross-sectional
      analysis utilized baseline data from the Behaviors Affecting Baby and You
      (B.A.B.Y.) study conducted among prenatal care patients at high risk for GDM
      (personal history of GDM or family history of diabetes and body mass index [BMI]
      >= 25 kg/m2). Smoking was assessed using questions from the Pregnancy Risk
      Assessment Monitoring System questionnaire and sedentary behavior (top vs. lower
      quartiles) and moderate/vigorous physical activity (bottom vs. upper quartile)
      via the Pregnancy Physical Activity Questionnaire. Results Participants (n = 400)
      enrolled at a mean of 12.4 (SD 3.6) weeks gestation. A total of 150 (44.1%)
      engaged in one, 37 (10.9%) in two, and 4 (1.2%) in three risk behaviors. Lower
      household income and not having children at home were each associated with a 2-6
      fold increased odds of smoking, high sedentary behavior, and engaging in at least
      one risk behavior. Being married, Hispanic or of younger age was associated with
      a 2-6 fold reduced odds of smoking. BMI and personal history of GDM were not
      associated with risk behaviors. Conclusions for Practice Findings help
      characterize high risk groups and inform prenatal interventions targeting these
      health risk behaviors.

PMID- 29335907
TI  - Content of First Prenatal Visits.
AB  - Objective The purpose of this study was to examine the content of the first
      prenatal visit within an academic medical center clinic and to compare the topics
      discussed to 2014 American College of Obstetrics and Gynecologists guidelines for
      the initial prenatal visit. Methods Clinical interactions were audio recorded and
      transcribed (n = 30). A content analysis was used to identify topics discussed
      during the initial prenatal visit. Topics discussed were then compared to the
      2014 ACOG guidelines for adherence. Coded data was queried though the qualitative
      software and reviewed for accuracy and content. Results First prenatal visits
      included a physician, nurse practitioner, nurse midwife, medical assistant,
      medical students, or a combination of these providers. In general, topics that
      were covered in most visits and closely adhered to ACOG guidelines included
      vitamin supplementation, laboratory testing, flu vaccinations, and cervical
      cancer screening. Topics discussed less often included many components of the
      physical examination, education about pregnancy, and screening for an
      identification of psychosocial risk. Least number of topics covered included
      prenatal screening. Conclusions for Practice While the ACOG guidelines may
      include many components that are traditional in addition to those based on
      evidence, the guidelines were not closely followed in this study. Identifying new
      ways to disseminate information during the time constrained initial prenatal
      visit are needed to ensure improved patient outcomes.

PMID- 29335908
TI  - Surgery for Abdominal Well-Differentiated Liposarcoma.
AB  - OPINION STATEMENT: Retroperitoneal sarcomas are rare tumors of which liposarcoma
      is the most common histology. Surgical resection remains the mainstay of therapy,
      particularly for the well-differentiated subtype. They can grow to massive size
      before causing symptoms or detection. Well-differentiated liposarcoma, while
      having a negligible metastatic rate, is fraught with a high local recurrence
      rate, despite a complete surgical resection. Reasons for this are not completely
      known but may be related to a field defect of the retroperitoneal fat creating a
      niche for recurrence. These tumors are classically chemo- and radio-resistant.
      Surgical therapy of recurrences can be challenging, but remains the treatment of
      choice for well-differentiated liposarcoma. In an attempt to improve on survival
      and recurrence rates for retroperitoneal liposarcoma, an extended resection
      approach has been promoted by a few groups. This involves the en bloc resection
      of contiguous organs that are not macroscopically involved. While this has
      improved local recurrence rates, benefit for overall survival has not been
      demonstrated. Interestingly, the improvement in local recurrence rate appeared to
      be driven by histology and was most improved in the well-differentiated subtype
      compared to historical data. However, for well-differentiated liposarcomas that
      are multifocal, this approach may be less useful. The application of this
      approach still requires further study in terms of balancing increased morbidity
      of extended resection against the potential for multiple surgeries for
      recurrence.

PMID- 29335909
TI  - Persistent posterior seroma after laparoscopic repair of ventral abdominal wall
      hernias with expanded polytetrafluoroethylene mesh: prevalence, independent
      predictors and detached tacks : Retrospective review.
AB  - PURPOSE: A persistent seroma located posterior to a mesh (PPS) remains a little
      known complication after laparoscopic ventral hernia repair (LVHR). The aim of
      this large case series was to analyse the prevalence and clinical course as well
      as identify related factors and independent predictors of PPS. METHODS: All 1288
      adult patients who underwent a LVHR with an expanded polytetrafluoroethylene mesh
      (ePTFE) between January 2003 and July 2014 were reviewed. Those who underwent an
      abdominal computed tomography (CT) scan more than 3 months afterwards (n = 166)
      were included and their scans were analysed. The primary outcome measure was the
      prevalence of a PPS and its characteristics. The secondary outcome measures were
      identification of significantly related factors and independent predictors of
      PPS. RESULTS: A PPS was observed in 14 of 166 analysed CT scans (8.4%). Eleven
      patients were symptomatic; conservative treatment (wait-and-see policy) was
      successful in eight. Three underwent relaparoscopy with removal of a thick
      neoperitoneum. Several instances of tack and/or mesh detachment were identified
      on CT scans and during relaparoscopy. Independent predictors were: > 3 trocars
      (RR 5.0, 95% CI 1.6-15.8) and use of a mesh larger than > 300 cm2 (RR 9.9, 95% CI
      1.9-51.2). CONCLUSIONS: A PPS is a relatively common complication after LVHR with
      an ePTFE mesh of usually larger hernias. A "wait-and-see" approach seems
      justified in most cases. Some require laparoscopic excision of the thick
      neoperitoneum. A PPS can cause tack and mesh detachment but the clinical
      consequences are unclear. Recurrences have not been observed in this series.

PMID- 29335910
TI  - Duration and magnitude of postoperative risk of venous thromboembolism after
      planned inguinal hernia repair in men: a population-based cohort study.
AB  - PURPOSE: Little is known regarding the magnitude and timing of the risk of VTE
      following inguinal hernia surgery. We aimed to determine the absolute and
      relative rates of venous thromboembolism (VTE) following planned inguinal hernia
      repair. METHODS: We analysed male adults with a first inguinal hernia repair with
      no prior record of VTE from the Clinical Practice Research Datalink, linked to
      the Hospital Episode Statistics (2001-2011). Crude rates and adjusted hazard
      ratios (HR) of the first VTE were calculated using Cox regression analysis to
      compare specific time periods following the surgery compared to the general
      population. RESULTS: We identified 28,782 men who underwent an inguinal hernia
      repair with 53 (0.18%) having a first VTE in the 90 days following surgery. The
      overall rate of VTE in the first 90 days following surgery was 7.61 per 1000
      person years (pyrs) (95% CI 5.82-9.96). Increasing age, a body mass index > 30
      kg/m2 and an in-patient procedure were associated with an increased risk of VTE,
      when compared to the general population. The risk of VTE was highest in the 1st
      month following the surgery with a 2.3- (aHR 2.33; 95% CI 1.09-4.99) and 3.5-
      (aHR 3.47; 95% CI 2.07-5.83) fold increased risk compared to the general
      population for both day case and planned in-patient procedures, respectively.
      CONCLUSIONS: Reassuringly, the absolute rates of VTE following inguinal hernia
      repair are low. Patients should be informed that their peak risk of VTE is during
      the 1st month following the surgery. Further studies on the optimum duration of
      thromboprophylaxis following surgery are required in high-risk patients
      undergoing hernia repair.

PMID- 29335911
TI  - Biotechnology software in the digital age: are you winning?
AB  - There is a digital revolution taking place and biotechnology companies are slow
      to adapt. Many pharmaceutical, biotechnology, and industrial bio-production
      companies believe that software must be developed and maintained in-house and
      that data are more secure on internal servers than on the cloud. In fact, most
      companies in this space continue to employ large IT and software teams and
      acquire computational infrastructure in the form of in-house servers. This is due
      to a fear of the cloud not sufficiently protecting in-house resources and the
      belief that their software is valuable IP. Over the next decade, the ability to
      quickly adapt to changing market conditions, with agile software teams, will
      quickly become a compelling competitive advantage. Biotechnology companies that
      do not adopt the new regime may lose on key business metrics such as return on
      invested capital, revenue, profitability, and eventually market share.

PMID- 29335912
TI  - Unprecedented response to combination BRAF and MEK inhibitors in adult anaplastic
      ganglioglioma.

PMID- 29335913
TI  - Analyzing the interactions of mRNAs, miRNAs, lncRNAs and circRNAs to predict
      competing endogenous RNA networks in glioblastoma.
AB  - Cross-talk between competitive endogenous RNAs (ceRNAs) may play a critical role
      in revealing potential mechanisms of tumor development and physiology.
      Glioblastoma is the most common type of malignant primary brain tumor, and the
      mechanisms of tumor genesis and development in glioblastoma are unclear. Here, to
      investigate the role of non-coding RNAs and the ceRNA network in glioblastoma, we
      performed paired-end RNA sequencing and microarray analyses to obtain the
      expression profiles of mRNAs, lncRNAs, circRNAs and miRNAs. We identified that
      the expression of 501 lncRNAs, 1999 mRNAs, 2038 circRNAs and 143 miRNAs were
      often altered between glioblastoma and matched normal brain tissue. Gene ontology
      and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed on
      these differentially expressed mRNAs and miRNA-mediated target genes of lncRNAs
      and circRNAs. Furthermore, we used a multi-step computational framework and
      several bioinformatics methods to construct a ceRNA network combining mRNAs,
      miRNAs, lncRNAs and circRNA, based on co-expression analysis between the
      differentially expressed RNAs. We identified that plenty of lncRNAs, CircRNAs and
      their downstream target genes in the ceRNA network are related to glutamatergic
      synapse, suggesting that glutamate metabolism is involved in glioma biological
      functions. Our results will accelerate the understanding of tumorigenesis, cancer
      progression and even therapeutic targeting in glioblastoma.

PMID- 29335914
TI  - Accuracy and trending of non-invasive hemoglobin measurement during different
      volume and perfusion statuses.
AB  - The evolution of non-invasive hemoglobin measuring technology would save time and
      improve transfusion practice. The validity of pulse co-oximetry hemoglobin (SpHb)
      measurement in the perioperative setting was previously evaluated; however, the
      accuracy of SpHb in different volume statuses as well as in different perfusion
      states was not well investigated. The aim of this work is to evaluate the
      accuracy and trending of SpHb in comparison to laboratory hemoglobin (Lab-Hb)
      during acute bleeding and after resuscitation. Seventy patients scheduled for
      major orthopedic procedures with anticipated major blood loss were included.
      Radical-7 device was used for continuous assessment of SpHb, volume status [via
      pleth variability index (PVI)] and perfusion status [via perfusion index (PI)].
      Lab-Hb and SpHb were measured at three time-points, a baseline reading, after
      major bleeding, and after resuscitation. Samples were divided into fluid
      responsive and fluid non-responsive samples, and were also divided into high-PI
      and low-PI samples. Accuracy of SpHb was determined using Bland-Altman analysis.
      Trending of SpHb was evaluated using polar plot analysis. We obtained 210 time
      matched readings. Fluid non-responsive samples were 106 (50.5%) whereas fluid
      responsive samples were 104 (49.5%). Excellent correlation was reported between
      Lab-Hb and SpHb (r = 0.938). Excellent accuracy with moderate levels of agreement
      was also reported between both measures among all samples, fluid non-responsive
      samples, fluid-responsive samples, high-PI samples, and low-PI samples [Mean bias
      (limits of agreement): 0.01 (- 1.33 and 1.34) g/dL, - 0.08 (- 1.27 and 1.11)
      g/dL, 0.09 (- 1.36 and 1.54) g/dL, 0.01 (- 1.34 to 1.31) g/dL, and 0.04 (- 1.31
      to 1.39) g/dL respectively]. Polar plot analysis showed good trending ability for
      SpHb as a follow up monitor. In conclusion, SpHb showed excellent correlation
      with Lab-Hb in fluid responders, fluid non-responders, low-PI, and high PI
      states. Despite a favorable mean bias of 0.01 g/dL for SpHb, the relatively wide
      levels of agreement (- 1.3 to 1.3 g/dL) might limit its accuracy. SpHb showed
      good performance as a trend monitor.

PMID- 29335915
TI  - Phenylephrine and paradoxically increased muscle tissue oxygenation: is the
      mechanism related to local venoconstriction or augmented venous return?

PMID- 29335916
TI  - Association between obstructive sleep apnea and non-alcoholic fatty liver
      disease: a systematic review and meta-analysis.
AB  - The relationship between obstructive sleep apnea (OSA) and non-alcoholic fatty
      liver disease (NAFLD) has been an issue of great concern. The primary purpose of
      this study was to determine the influence of OSA on the levels of liver enzymes
      including alanine transaminase (ALT) and aspartate transaminase (AST). The
      secondary purpose was to estimate the effect of OSA on the histological lesions
      of NAFLD, such as steatosis, lobular inflammation, ballooning degeneration,
      fibrosis, as well as NAFLD activity score (NAS). A systematic literature review
      using PubMed, Cochrane Library, Embase, and Ovid technologies from January 2007
      to April 2017 was performed, and 9 studies (2272 participants) that met the
      selection criteria were evaluated. The present study demonstrated that OSA was
      related to ALT levels, but no significant correlation was found with AST levels.
      The subgroup analysis showed that the severity of OSA was associated with ALT
      levels, not with AST levels. The meta-regression analysis showed that age, sex,
      homeostasis model assessment, diabetes mellitus, body mass index, and waist
      circumference did not have a significant effect on the levels of ALT and AST. OSA
      was also found to be significantly correlated with steatosis, lobular
      inflammation, ballooning degeneration, and fibrosis, but was not correlated with
      NAS. OSA was independently related to the development and progression of NAFLD in
      terms of liver enzyme level and histological alterations. Future studies should
      investigate the possible relevant mechanisms, thereby guiding the exploration of
      potential therapeutic implications to prevent the progression of disease.

PMID- 29335917
TI  - Basal sympathetic predominance in periodic limb movements in sleep after
      continuous positive airway pressure.
AB  - PURPOSE: This study investigated the basal autonomic regulation in patients with
      obstructive sleep apnea (OSA) showing periodic limb movements in sleep (PLMS)
      emerging after therapy with continuous positive airway pressure (CPAP). METHODS:
      Data of patients with OSA undergoing a first polysomnography for diagnosis and a
      second polysomnography for therapy with CPAP were reviewed. Patients with OSA
      showing PLMS on the first polysomnography were excluded. By using heart rate
      variability analysis, epochs without any sleep events and continuous effects from
      the second polysomnography were retrospectively analyzed. RESULTS: Of 125
      eligible patients, 30 with PLMS after therapy with CPAP (PLMS group) and 30 not
      showing PLMS on both polysomnography (non-PLMS group) were randomly selected for
      the analysis. No significant differences in the demographic characteristics and
      variables of polysomnographies were identified between the groups. Although one
      trend of low root mean square of successive differences (RMSSD) between intervals
      of adjacent normal heart beats (NN intervals) in the PLMS group was observed,
      patients in the PLMS group had significantly low normalized high-frequency (n-HF)
      and high-frequency (HF) values, but high normalized low frequency (n-LF) and high
      ratio of LF to HF (LF/HF ratio). After adjustment for confounding variables, PLMS
      on the second polysomnography was significantly associated with RMSSD (beta = -
      6.7587, p = 0.0338), n-LF (beta = 0.0907, p = 0.0148), n-HF (beta = - 0.0895, p =
      0.0163), log LF/HF ratio (beta = 0.4923, p = 0.0090), and log HF (beta = -
      0.6134, p = 0.0199). CONCLUSIONS: Patients with OSA showing PLMS emerging after
      therapy with CPAP may have a basal sympathetic predominance with potential
      negative cardiovascular effects.

PMID- 29335919
TI  - Inter- and intracellular colonization of Arabidopsis roots by endophytic
      actinobacteria and the impact of plant hormones on their antimicrobial activity.
AB  - Many actinobacteria live in close association with eukaryotes such as fungi,
      insects, animals and plants. Plant-associated actinobacteria display
      (endo)symbiotic, saprophytic or pathogenic life styles, and can make up a
      substantial part of the endophytic community. Here, we characterised endophytic
      actinobacteria isolated from root tissue of Arabidopsis thaliana (Arabidopsis)
      plants grown in soil from a natural ecosystem. Many of these actinobacteria
      belong to the family of Streptomycetaceae with Streptomyces olivochromogenes and
      Streptomyces clavifer as well represented species. When seeds of Arabidopsis were
      inoculated with spores of Streptomyces strain coa1, which shows high similarity
      to S. olivochromogenes, roots were colonised intercellularly and, unexpectedly,
      also intracellularly. Subsequent exposure of endophytic isolates to plant
      hormones typically found in root and shoot tissues of Arabidopsis led to altered
      antibiotic production against Escherichia coli and Bacillus subtilis. Taken
      together, our work reveals remarkable colonization patterns of endophytic
      streptomycetes with specific traits that may allow a competitive advantage inside
      root tissue.

PMID- 29335920
TI  - Clergy's Beliefs About Mental Illness and Their Perception of Its Treatability:
      Experience from a Church-Based Prevention of Mother-to-Child HIV Transmission
      (PMTCT) Trial in Nigeria.
AB  - Clergy participating in the Healthy Beginning Initiative (N = 45), a program
      utilizing church workers to integrate packages of care into church activities,
      completed a 43-item self-administered questionnaire assessing their attitudes and
      beliefs about mental disorders and perception of their treatability. A majority
      believed that drug/alcohol use, stress and genetic inheritance could cause mental
      illness and that society needed to adopt more tolerant attitude toward people
      with mental disorders. Clergy with contact with people with mental disorders were
      more likely to perceive depression as treatable. In conclusion, participants had
      positive attitudes toward mental disorders with some believing that they are
      treatable.

PMID- 29335921
TI  - Development of real-time PCR assay for the detection of Mycoplasma bovis.
AB  - Mycoplasma bovis is one of the important bovine mycoplasma involved in
      economically important clinical conditions like respiratory diseases, otitis
      media, and mastitis. The present study was undertaken with the objective of
      developing a SYBR Green dye-based real-time PCR assay targeting uvrC gene for the
      diagnosis of M. bovis. The analytical sensitivity and specificity of the assay
      were evaluated. The test showed 103-fold more sensitivity than conventional PCR
      and detected down to 100 fg level of DNA. It was found to be specific, as no
      cross reactivity was shown with other related bacteria and Mycoplasma species.
      The developed assay was able to detect down to 40 copies of uvrC gene from spiked
      bovine milk samples. At present, this developed assay may be used as a valuable
      diagnostic tool for the detection of Mycoplasma bovis.

PMID- 29335922
TI  - Breast conserving surgery in combination with intraoperative radiotherapy after
      previous external beam therapy: an option to avoid mastectomy.
AB  - PURPOSE: Mastectomy is the standard procedure in patients with in-breast tumor
      recurrence (IBTR) or breast cancer after irradiation of the chest due to
      Hodgkin's disease. In certain cases a second breast conserving surgery (BCS) in
      combination with intraoperative radiotherapy (IORT) is possible. To date, data
      concerning BCS in combination with IORT in pre-irradiated patients are limited.
      This is the first pooled analysis of this special indication with a mature follow
      up of 5 years. METHODS: Patients with IBTR after external beam radiotherapy
      (EBRT; treated in two centers) for breast cancer were included. Patients with
      previous EBRT including the breast tissue due to other diseases were also
      included. IORT was performed with the IntrabeamTM-device using low kV X-rays.
      Clinical data including outcome for all patients and toxicity for a
      representative cohort (LENT-SOMA scales) were obtained. Statistical analyses were
      done including Kaplan-Meier estimates for local recurrence, distant metastasis
      and overall survival. RESULTS: A total of 41 patients were identified (39
      patients with IBTR, 2 with Hodgkin's disease in previous medical history). Median
      follow-up was 58 months (range 4-170). No grade 3/4 acute toxicity occurred
      within 9 weeks. Local recurrence-free survival rate was 89.9% and overall
      survival was 82.7% at 5 years. Seven patients developed metastasis within the
      whole follow-up. CONCLUSIONS: BCS in combination with IORT in IBTR in pre
      irradiated patients is a feasible method to avoid mastectomy with a low risk of
      side effects and an excellent local control and good overall survival.

PMID- 29335923
TI  - How reliable are the available safety data on hormonal stimulation for fertility
      preservation in young women with newly diagnosed early breast cancer?

PMID- 29335924
TI  - BRCA1 and BRCA2 germline variants in breast cancer patients from the Republic of
      Macedonia.
AB  - PURPOSE: We aimed to establish the spectrum of BRCA1/2 mutations among the breast
      cancer (BC) patients from the Republic of Macedonia. METHODS: We used targeted
      next-generation sequencing (NGS), Sanger DNA sequencing, and multiplex ligation
      probe amplification analysis (MLPA) to search for point mutations and
      deletions/duplications involving BRCA1 and BRCA2-coding regions. RESULTS: We have
      analyzed a total of 313 BC patients, enriched for family history of cancer, early
      age of onset and bilateral and/or triple negative (TN) BC. A total of 26
      pathogenic mutations were observed in 49 unrelated BC patients (49/313, 15.7%).
      BRCA2 mutations (27/49, 55.1%) were more common than BRCA1 mutations (22/49,
      44.9%). We identified five novel point mutations, one in BRCA1 (c.4352_4356delA)
      and four in BRCA2 (c.151G>T, c.4707_4708delCA, c.7811_7814delTGTG, and
      c.9304_9305delG), as well as two novel deletions involving parts of the BRCA1
      gene (c.81-?_593+?del and c.5470-?_5530+?del). The most common mutations were
      c.181T>G, c.5266dupC, and c.3700_3704del5 in BRCA1 and c.7879A>T,
      c.8317_8330del14 and c.5722_5723delCT in BRCA2 gene. Thus far, BRCA2 c.7879A>T
      and c.8317_8330del14 mutations have been described in several isolated cases;
      however, our study is the first one showing that they have a founder effect among
      Macedonian population. Nine recurrent mutations account for 65.3% of all of the
      detected mutations allowing for implementation of a fast first-step BRCA1/2
      mutational screening strategy in our country. CONCLUSION: This study provides a
      comprehensive view of known and novel BRCA1/2 mutations in BC patients from the
      Republic of Macedonia and contributes to the global spectrum of BRCA1/2 mutations
      in breast cancer.

PMID- 29335925
TI  - Germline deleterious mutations in genes other than BRCA2 are infrequent in male
      breast cancer.
AB  - PURPOSE: Male breast cancer (MBC) is a rare cancer entity, with mutations in
      BRCA1 and BRCA2 genes accounting for ~ 10% of patients. Multiple-gene sequencing
      has already entered clinical practice for female breast cancer, whereas the
      performance of panel testing in MBC has not been studied extensively. Therefore,
      the aim of this study was to evaluate the clinical utility of panel testing for
      MBC, by the largest gene panel used so far, through investigation of patients
      deriving from a population with known founder effects. METHODS: Genomic DNA from
      one hundred and two Greek MBC patients, unselected for age and family history,
      was used to prepare libraries which capture the entire coding regions of 94
      cancer genes. RESULTS: Loss-of-function (LoF) mutations were found in 12.7% of
      the cases, distributed in six genes: BRCA2, ATM, BRCA1, CHEK2, PMS2, and FANCL.
      BRCA2 mutations were the most frequent, followed by ATM mutations, accounting for
      6.9 and 2%, respectively, while mutations in other genes were detected in single
      cases. Age at diagnosis or family history was not predictive of mutation status.
      Beyond mutations in established breast cancer predisposing genes, LoF mutations
      in PMS2 and FANCL among MBC patients are reported here for the first time.
      CONCLUSIONS: Our findings, using the largest gene panel for MBC patients so far,
      indicate that BRCA testing should be the primary concern for MBC patients. Until
      sufficient evidence arises from larger studies, multiple-gene panels may be of
      limited benefit for MBC and their families, at least for MBC patients of specific
      descent.

PMID- 29335926
TI  - ?

PMID- 29335927
TI  - miRNAs as Potential Treatment Targets and Treatment Options in Cancer.
AB  - Standard cancer therapies for solid malignancies, such as chemotherapy and
      radiotherapy, are not target specific against cancer cells and are often not
      fully efficacious. Chemotherapy and radiotherapy may cause side effects, and the
      need to develop additional strategies for cancer treatment is urgent. MicroRNAs
      (miRNAs) are small non-coding RNAs with heterogeneous functions and have been
      described in almost every known cancer model. Besides their basic tumor
      suppressive and oncogenic functions, they also have the potential to modulate
      chemotherapy and radiotherapy and to be manipulated with chemical compounds to
      make them chemically suitable for efficient delivery to cancer cells. It has been
      suggested that the level of expression of specific miRNAs could increase
      treatment efficacy by determining the stage of chemotherapy/radiotherapy
      sensitivity. Application of miRNAs alone or in combination with standard
      therapeutic strategies may significantly improve the success of cancer treatments
      in the future.

PMID- 29335928
TI  - CT imaging of primary pancreatic lymphoma: experience from three referral centres
      for pancreatic diseases.
AB  - PURPOSE: To describe CT characteristics of primary pancreatic lymphoma (PPL), a
      rare disease with features in common with adenocarcinoma. MATERIALS AND METHODS:
      Fourteen patients were enrolled. CT: unenhanced scan, contrast-enhanced
      pancreatic and venous phases. Image analysis: tumour location; peri-pancreatic
      vessel encasement; necrosis; enlarged lymph nodes; fat stranding; enlarged bile
      duct and pancreatic duct; neoplasm longest dimension, volume and density.
      RESULTS: Histopathological diagnoses: follicular non-Hodgkin lymphoma (5/14),
      diffuse large B-cell lymphoma (6/14) and high-grade B-cell lymphoma not otherwise
      specified (3/14). Six of 14 PPLs were located in the pancreatic head and 7/14 in
      the body-tail; 1/14 involved the whole gland. In 5/14 cases the superior
      mesenteric artery and vein were encased; splenic vein and artery encasement was
      depicted in 2 PPLs. Necrosis was present in 2/14. Enlarged retroperitoneal lymph
      nodes were found in 11 cases and fat stranding in all patients. The bile duct was
      dilated in six cases and the pancreatic duct in five. Mean neoplasm longest
      diameter and volume were 8.05 cm and 210.8 cm3. Mean tumour attenuation values
      were 39.1 HU at baseline, 60.6 HU in the pancreatic phase and 71.4 HU in the
      venous phase. CONCLUSIONS: PPL presents as a large mass lesion with delayed
      homogeneous enhancement; peri-pancreatic fat stranding and vessel encasement are
      present, without vascular infiltration. Pancreatic duct dilatation is rare. KEY
      POINTS: * Primary pancreatic lymphoma (PPL) is a rare haematological disease *
      PPL presents imaging features in common with pancreatic carcinoma but also some
      distinctive findings * The majority of PPLs are large lesions with delayed
      homogeneous enhancement * Peri-pancreatic fat stranding and vessel encasement are
      common in PPL * Vascular infiltration and pancreatic duct dilatation are rare in
      PPL.

PMID- 29335930
TI  - [Comments and supplement : Leukopenia and agranulocytosis under antirheumatic
      drug treatment in HLA B27 positive patients].

PMID- 29335929
TI  - Computational model to investigate the relative contributions of different
      neuromuscular properties of tibialis anterior on force generated during ankle
      dorsiflexion.
AB  - This study describes a new model of the force generated by tibialis anterior
      muscle with three new features: single-fiber action potential, twitch force, and
      pennation angle. This model was used to investigate the relative effects and
      interaction of ten age-associated neuromuscular parameters. Regression analysis
      (significance level of 0.05) between the neuromuscular properties and
      corresponding simulated force produced at the footplate was performed.
      Standardized slope coefficients were computed to rank the effect of the
      parameters. The results show that reduction in the average firing rate is the
      reason for the sharp decline in the force and other factors, such as number of
      muscle fibers, specific force, pennation angle, and innervation ratio. The fast
      fiber ratio affects the simulated force through two significant interactions.
      This study has ranked the individual contributions of the neuromuscular factors
      to muscle strength decline of the TA and identified firing rate decline as the
      biggest cause followed by decrease in muscle fiber number and specific force. The
      strategy for strength preservation for the elderly should focus on improving
      firing rate. Graphical abstract Neuromuscular properties of Tibialis Anterior on
      force generated during ankle dorsiflexion.

PMID- 29335931
TI  - [Indications for joint replacement : Knee arthroplasty].
AB  - Current demographic trends with an increasing number of older patients, have led
      to a rising number of patients with higher demands on performance. Osteoarthritis
      in younger patients caused by abnormal forms or accidents also pose new
      challenges for medical professionals in the orthopedic field. As a rule of thumb,
      all conservative therapeutic possibilities should be exhausted before starting a
      surgical intervention. The main aims of surgery are to reduce pain, increase
      mobility and quality of life. In order to qualify for total knee arthroplasty
      (TKA) patients must fulfil major and minor criteria; however, after TKA
      approximately one fifth of patients are not satisfied with the result. In order
      to reduce this rate, indications should be narrowly set and expectations should
      be thoroughly discussed with the patient prior to an intervention. The high
      degree of dissatisfaction must be improved by intensifying efforts in further
      research.

PMID- 29335932
TI  - The EURO-FORTA (Fit fOR The Aged) List: International Consensus Validation of a
      Clinical Tool for Improved Drug Treatment in Older People.
AB  - BACKGROUND: Drug treatment of older people is still potentially inappropriate in
      many cases as multimorbidity and related polypharmacy are highly prevalent. To
      increase the quality of drug treatment in older people, the FORTA (Fit fOR The
      Aged) List (first version 2012) was developed in a Delphi consensus procedure and
      updated (FORTA2015) by 21 experts from Germany and Austria. It has been validated
      in a randomized, controlled, prospective trial demonstrating significant
      improvement in the quality of drug treatment and clinical endpoints (VALFORTA).
      METHODS: Based on these results, Delphi consensus validations (two rounds) of
      country/region-specific FORTA Lists were conducted in the UK/Ireland, France,
      Poland, Italy, Spain, the Nordic countries and The Netherlands. An algorithm
      based on geriatric/pharmacologic expertise, publications and professional
      position was used to find experts in the field. RESULTS: Forty-seven experts
      agreed to participate in the Delphi process (return rate of 97.9%). For each
      country/region, the overall mean consensus coefficient (deviation from the
      initiator proposal) was > 0.9. FORTA Lists from six countries/regions with a
      minimum of four participating experts (excluding The Netherlands) plus the
      original FORTA List were collated into the EURO-FORTA List containing 264 items
      in 26 main indication groups. Two drugs had to be added to the proposed items, as
      proposed by at least four countries/regions; none had to be removed. CONCLUSION:
      This project produced seven new country/region-specific FORTA Lists, as well as
      the overarching EURO-FORTA List showing a high consensual level based on a
      broader expert base. EURO-FORTA should help to spread the FORTA approach and
      improve geriatric pharmacotherapy internationally.

PMID- 29335933
TI  - Cost-Effectiveness Analysis of Bariatric Surgery for Morbid Obesity.
AB  - BACKGROUND: In the USA, three types of bariatric surgeries are widely performed,
      including laparoscopic sleeve gastrectomy (LSG), laparoscopic Roux-en-Y gastric
      bypass (LRYGB), and laparoscopic adjustable gastric banding (LAGB). However, few
      economic evaluations of bariatric surgery are published. There is also scarcity
      of studies focusing on the LSG alone. Therefore, this study is evaluating the
      cost-effectiveness of bariatric surgery using LRYGB, LAGB, and LSG as treatment
      for morbid obesity. METHODS: A microsimulation model was developed over a
      lifetime horizon to simulate weight change, health consequences, and costs of
      bariatric surgery for morbid obesity. US health care prospective was used. A
      model was propagated based on a report from the first report of the American
      College of Surgeons. Incremental cost-effectiveness ratios (ICERs) in terms of
      cost per quality-adjusted life-year (QALY) gained were used in the model. Model
      parameters were estimated from publicly available databases and published
      literature. RESULTS: LRYGB was cost-effective with higher QALYs (17.07) and cost
      ($138,632) than LSG (16.56 QALYs; $138,925), LAGB (16.10 QALYs; $135,923), and no
      surgery (15.17 QALYs; $128,284). Sensitivity analysis showed initial cost of
      surgery and weight regain assumption were very sensitive to the variation in
      overall model parameters. Across patient groups, LRYGB remained the optimal
      bariatric technique, except that with morbid obesity 1 (BMI 35-39.9 kg/m2)
      patients, LSG was the optimal choice. CONCLUSION: LRYGB is the optimal bariatric
      technique, being the most cost-effective compared to LSG, LAGB, and no surgery
      options for most subgroups. However, LSG was the most cost-effective choice when
      initial BMI ranged between 35 and 39.9 kg/m2.

PMID- 29335934
TI  - The Predictive Factors for Diabetic Remission in Chinese Patients with BMI > 30
      kg/m2 and BMI < 30 kg/m2 Are Different.
AB  - INTRODUCTION: Roux-en-Y gastric bypass has been proven to be beneficial for
      patients with obesity and type 2 diabetes mellitus (T2DM). In less-obese patient
      (BMI 30-35 kg/m2), surgical treatment is indicated when medication fails to
      control the T2DM. Asian develops diabetes at a lower BMI. For lower-BMI patients,
      the rate of diabetes amelioration varies significantly with patients of higher
      BMI after surgical treatment. The factors that contribute to the post-operative
      diabetes response rate in lower-BMI patients have not been elucidated. METHODS:
      Between 2010 and 2014, a total of 144 patients who underwent gastric bypass for
      the treatment of T2DM were included for study. Patients were divided into two
      groups for subgroup analysis, namely BMI > 30 kg/m2 and BMI < 30 kg/m2. Factors
      affecting the remission rate were examined. RESULTS: Of the studied patients, the
      DM remission rate for the high-BMI group (BMI > 30 kg/m2) was 80% (n = 90)
      whereas for the lower BMI (BMI < 30 kg/m2) was 50% (n = 54), p < 0.001. For high
      BMI group, low HbA1c and high fasting C-peptide are predictive factors whereas
      for lower-BMI group, along with elevated C-peptide level, disease duration is the
      positive predictive factor for DM remission. CONCLUSION: Patients with BMI > 30
      kg/m2 and those with BMI < 30 kg/m2 have distinct remission predicting factors.
      Low HbA1c is a predictor of remission in low-high-BMI patients while duration of
      diabetes is for high-low-BMI patients. C-peptide is a predictor of remission in
      both groups. Further large-scale studies are required to define the predictors of
      diabetes remission after gastric bypass in low- and high-BMI patients.

PMID- 29335935
TI  - ?

PMID- 29335936
TI  - ?

PMID- 29335937
TI  - ?

PMID- 29335938
TI  - [Diabetes and infection - a missing link really?]

PMID- 29335939
TI  - [E-cigarettes: in urgent cases an acceptable alternative].

PMID- 29335940
TI  - [The human intestinal microbiome and why you have to think twice before
      prescribing antibiotics!]

PMID- 29335941
TI  - ?

PMID- 29335942
TI  - [Lipoprotein (a) - what to do?]

PMID- 29335943
TI  - [PCSK9 inhibitors: For which patients? For which indication? What to consider?]

PMID- 29335944
TI  - [Statin-associated muscle symptoms].

PMID- 29335945
TI  - ?

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PMID- 29335999
TI  - [Rheumatoid arthritis].

PMID- 29336000
TI  - The Origin and Ecological Function of an Ion Inducing Anti-Predator Behavior in
      Lithobates Tadpoles.
AB  - In aquatic environments, chemical cues are believed to be associated with prey
      response to predation risk, yet few basic cue compositions are known despite the
      pronounced ecological and evolutionary significance of such cues. Previous work
      indicated that negatively-charged ions of m/z 501 are possibly a kairomone that
      induces anti-predator responses in amphibian tadpoles. However, work described
      here confirms that this specific ion species m/z 501.2886 is produced by injured
      tadpoles, exhibits increased spectral intensity with higher tadpole biomass, and
      is not produced by starved predators. These results indicate the anion is an
      alarm cue released from tadpoles. High resolution mass spectrometry (HR-MS)
      revealed a unique elemental composition for [M-H]-, m/z 501.2886, of C26H45O7S-
      which could not be determined in previous studies using low resolution
      instruments. Collision induced dissociation of m/z 501 ions formed product ions
      of m/z 97 and m/z 80, HSO4- and SO3-, respectively, showing the presence of
      sulfate. Green frog tadpoles, Lithobates clamitans, exposed to the m/z 501 anion
      or sodium dodecyl sulfate exhibited similar anti-predator responses, suggesting
      organic sulfate is a tadpole behavior modifier.

PMID- 29336001
TI  - Advances in the Study of the Middle Cranial Fossa through Cutting Edge
      Neuroimaging Techniques.
AB  - The objective of this paper is to present a morphometric study of the middle
      cranial fossa from the study of 87 patients using cutting edge multislice
      computed tomography scans (32 detectors) and Magnetic Resonance Imaging. The
      study presents a detailed anatomical-radiological and morphometric analysis of
      the middle cranial fossa as well as its neurovascular elements in normal
      conditions. The implications of this investigation in training and clinical
      contexts are discussed.

PMID- 29336003
TI  - Prevalence of pre-school children for overweight/obesity in Turkey.
AB  - BACKGROUND: Most of the studies and interventions are targeted to address
      undernutrition, but childhood obesity has become a silent killer among children.
      Developing countries, including Turkey, could recognize the importance of the
      issue now and have begun to discuss the necessity of studies on this subject.
      Therefore, this study aims to examine the prevalence of obesity among pre-school
      children in Turkey. METHODS: The data source of this study is the Turkey
      Demographic and Health Survey (TDHS)-2013. The TDHS-2013 was a sample study to
      gather information about the fertility levels and changes in them, infant and
      child mortality, family planning, and maternal and infant health at the national
      level. RESULTS: Overweight/obesity for height was 8.6% and 6.6% for age.
      Overweight/obesity problems are mostly observed in the West and are higher in
      urban areas. Overweight/obesity decreases with increasing age. There is a
      positive correlation between overweight/obesity and maternal educational level.
      As the household welfare level increases, overweight/obesity increases in pre
      school children. Female children are at higher risk of overweight/obesity than
      males. As birth order increases, overweight/obesity decreases. Children living in
      other regions have overweight/obesity problems more than the pre-school children
      living in the East. CONCLUSIONS: This study speculates that obesity appears to be
      a major problem among pre-school children in Turkey. Based on the findings, the
      current situation of overweight/obesity among pre-school children is so close to
      many developing and developed countries, whose obesity levels are a greater
      concern. This finding demonstrates that effective interventions of obesity should
      begin as early as infancy in Turkey, as it is a developing country.

PMID- 29336002
TI  - Body composition and circulating estradiol are the main bone density predictors
      in healthy young and middle-aged men.
AB  - PURPOSE: Current fracture risk assessment options in men call for improved
      evaluation strategies. Recent research directed towards non-classic bone mass
      determinants have often yielded scarce and conflicting results. We aimed at
      investigating the impact of novel potential bone mass regulators together with
      classic determinants of bone status in healthy young and middle-aged men.
      METHODS: Anthropometric measurements, all-site bone mineral density (BMD) and
      body composition parameters assessed by dual-energy X-ray absorptiometry and also
      serum concentrations of (1) the adipokines leptin and resistin, (2) vitamin D and
      parathormone (PTH), (3) sex hormone binding globulin (SHBG), total testosterone
      and estradiol (free testosterone was also calculated) and (4) C-terminal
      telopeptide of type I collagen (CTx) were obtained from 30 apparently healthy
      male volunteers aged 20-65 years enrolled in this cross-sectional study. RESULTS:
      Only lean mass (LM) and total estradiol independently predicted BMD in men in
      multiple regression analysis, together explaining 49% (p <= 0.001) of whole-body
      BMD variance. Hierarchical regression analysis with whole-body BMD as outcome
      variable demonstrated that the body mass index (BMI) beta coefficient became
      nonsignificant when LM was added to the model. Adipokines, fat parameters,
      testosterone (total and free), SHBG, PTH and vitamin D were not independently
      associated with BMD or CTx. CONCLUSIONS: The present study shows that LM and sex
      hormones-namely estradiol-are the main determinants of bone mass in young and
      middle-aged men. The effects of BMI upon BMD seem to be largely mediated by LM.
      Lifestyle interventions should focus on preserving LM in men for improved bone
      outcomes.

PMID- 29336004
TI  - Point-of-Care Urine Ethyl Glucuronide Testing to Detect Alcohol Use Among HIV
      Hepatitis B Virus Coinfected Adults in Zambia.
AB  - In an HIV-hepatitis B virus (HIV-HBV) coinfection cohort in Zambia, we piloted a
      qualitative point-of-care (POC) test for urine Ethyl glucuronide (uEtG), assessed
      concordance between uEtG and alcohol use disorders identification test
      consumption (AUDIT-C), and identified epidemiological factors associated with
      underreporting (defined as uEtG-positivity with last reported drink > 7 days
      prior). Among 211 participants (40.8% women), there were 44 (20.8%) lifetime
      abstainers, 32 (15.2%) former drinkers, and 135 (64.0%) current drinkers,
      including 106 (50.2%) with unhealthy drinking per AUDIT-C. Eighty-seven (41.2%)
      were uEtG-positive including 64 of 65 (98.5%) who drank <= 3 days prior and 17 of
      134 (12.7%) underreported, all of whom admitted to recent drinking when results
      were discussed. uEtG was moderately concordant with AUDIT-C. Past drinking
      (versus lifetime abstinence) and longer time on antiretrovirals (>= 12 months)
      were associated with underreporting. These data support further use of POC
      alcohol biomarkers in HIV and hepatitis research and clinical settings.

PMID- 29336006
TI  - The place of frailty and vulnerability in the surgical risk assessment: should we
      move from complexity to simplicity?
AB  - Due to aging of the world population, older patients accessing health services
      are becoming continuously more frequent. This has increased the interest in
      assessing frailty and vulnerability in all specialties and general medicine.
      Although the term frailty has been recognized for over 30 years, there is not yet
      a universally recognized definition, and different care providers assess frailty
      and vulnerability with dissimilar tools, from very complex to very simple
      validated scales. Being treated with respect and dignity at the right time and
      place is the key message, as well as after undergoing a global evaluation both in
      urgency/emergency and in programmed surgery for all older surgical patients.
      Filling the gap will improve the results of any clinical intervention, both
      medical and surgical. Anesthesiologists, surgeons, hospitalists, and any member
      of the team of care providers must be trained into geriatric syndromes.

PMID- 29336005
TI  - Degranulation inhibitors from the arils of Myristica fragrans in antigen
      stimulated rat basophilic leukemia cells.
AB  - A methanol extract of mace, the aril of Myristica fragrans (Myristicaceae), was
      found to inhibit the release of beta-hexosaminidase, a marker of antigen-IgE
      stimulated degranulation in rat basophilic leukemia cells (RBL-2H3, IC50 = 45.7
      MUg/ml). From the extract, three new 8-O-4' type neolignans, maceneolignans I-K
      (1-3), were isolated, and the stereostructures of 1-3 were elucidated based on
      spectroscopic and chemical evidence. Among the isolates, maceneolignans A (5), D
      (6), and H (8), (-)-(8R)-?8'-4-hydroxy-3,3',5'-trimethoxy-8-O-4'-neolignan (13),
      (-)-(8R)-?8'-3,4,5,3',5'-pentamethoxy-8-O-4'-neolignan (14), (-)-erythro-(7R,8S)
      ?8'-7-acetoxy-3,4-methylenedioxy-3',5'-dimethoxy-8-O-4'-neolignan (17), (+)
      licarin A (20), nectandrin B (24), verrucosin (25), and malabaricone C (29) were
      investigated as possible degranulation inhibitors (IC50 = 20.7-63.7 MUM). These
      inhibitory activities were more potent than those of the antiallergic agents
      tranilast (282 MUM) and ketotifen fumalate (158 MUM). Compounds 5, 25, and 29
      also inhibited antigen-stimulated tumor necrosis factor-alpha production (IC50 =
      39.5-51.2 MUM), an important process in the late phase of type I allergic
      reactions.

PMID- 29336007
TI  - Vulvo-vaginal rejuvenation: Fact or fiction? Fractional carbon dioxide laser for
      genitourinary syndrome of menopause.

PMID- 29336008
TI  - Dermatology training across the globe.

PMID- 29336009
TI  - Gefitinib for advanced non-small cell lung cancer.
AB  - BACKGROUND: The role of gefitinib for the treatment of advanced non-small cell
      lung cancer (NSCLC) is evolving. We undertook a systematic review to evaluate the
      available evidence from all randomised trials. OBJECTIVES: To determine the
      effectiveness and safety of gefitinib as first-line, second-line or maintenance
      treatment for advanced NSCLC. SEARCH METHODS: We performed searches in CENTRAL,
      MEDLINE and Embase from inception to 17 February 2017. We handsearched relevant
      conference proceedings, clinical trial registries and references lists of
      retrieved articles. SELECTION CRITERIA: We included trials assessing gefitinib,
      alone or in combination with other treatment, compared to placebo or other
      treatments in the first- or successive-line treatment of patients with NSCLC,
      excluding compassionate use. DATA COLLECTION AND ANALYSIS: We used the standard
      Cochrane methodology. Two authors independently assessed the search results to
      select those with sound methodological quality. We carried out all analyses on an
      intention-to-treat basis. We recorded the following outcome data: overall
      survival, progression-free survival, toxicity, tumour response and quality of
      life. We also collected data for the following subgroups: Asian ethnicity and
      positive epidermal growth factor receptor (EGFR) mutation. MAIN RESULTS: We
      included 35 eligible randomised controlled trials (RCTs), which examined 12,089
      patients.General populationGefitinib did not statistically improve overall
      survival when compared with placebo or chemotherapy in either first- or second
      line settings. Second-line gefitinib prolonged time to treatment failure (TTF)
      (hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.75 to 0.90, P < 0.0001)
      when compared with placebo. Maintenance gefitinib improved progression-free
      survival (HR 0.70, 95% CI 0.53 to 0.91, P = 0.007) after first-line
      therapy.Studies in patients of Asian ethnicity or that conducted subgroup
      analysesSecond-line gefitinib prolonged overall survival over placebo (HR 0.66,
      95% CI 0.48 to 0.91, P = 0.01). In the first-line setting, progression-free
      survival was improved with gefitinib over chemotherapy alone (HR 0.65, 95% CI
      0.43 to 0.98, P = 0.04, moderate quality of evidence). Gefitinib given in
      combination with a chemotherapy regimen improved progression-free survival versus
      either gefitinib alone or chemotherapy alone (HR 0.69, 95% CI 0.49 to 0.96, P =
      0.03; HR 0.69, 95% CI 0.62 to 0.77, P < 0.00001, respectively). In the second
      line setting, progression-free survival was superior in patients given gefitinib
      over placebo or chemotherapy (HR 0.69, 95% CI 0.52 to 0.91, P = 0.009; HR 0.71,
      95% CI 0.57 to 0.88, P = 0.002; moderate quality of evidence, respectively).
      Combining gefitinib with chemotherapy in the second-line setting was superior to
      gefitinib alone (HR 0.65, 95% CI 0.43 to 0.97, P = 0.04). As maintenance therapy,
      gefitinib improved progression-free survival when compared with placebo (HR 0.42,
      95% CI 0.33 to 0.54, P < 0.00001).Patients with EGFR mutation-positive
      tumoursStudies in patients with EGFR mutation-positive tumours showed an
      improvement in progression-free survival in favour of gefitinib over first-line
      and second-line chemotherapy (HR 0.47, 95% CI 0.36 to 0.61, P < 0.00001; HR 0.24,
      95% CI 0.12 to 0.47, P < 0.0001, respectively). Gefitinib as maintenance therapy
      following chemotherapy improved overall and progression-free survival (HR 0.39,
      95% CI 0.15 to 0.98, P = 0.05; HR 0.17, 95% CI 0.07 to 0.41, P < 0.0001,
      respectively) in one phase III study when compared to placebo.Toxicities from
      gefitinib included skin rash, diarrhoea and liver transaminase derangements.
      Toxicities from chemotherapy included anaemia, neutropenia and neurotoxicity.In
      terms of quality of life, gefitinib improved Functional Assessment of Cancer
      Therapy-Lung (FACT-L) (standardised mean difference (SMD) 10.50, 95% CI 9.55 to
      11.45, P < 0.000001), lung cancer subscale (SMD 3.63, 95% CI 3.08 to 4.19, P <
      0.00001) and Trial Outcome Index (SMD 9.87, 95% CI 1.26 to 18.48, P < 0.00001)
      scores when compared with chemotherapy. AUTHORS' CONCLUSIONS: This systematic
      review shows that gefitinib, when compared with standard first- or second-line
      chemotherapy or maintenance therapy, probably has a beneficial effect on
      progression-free survival and quality of life in selected patient populations,
      particularly those with tumours bearing sensitising EGFR mutations.Patients with
      EGFR mutations lived longer when given maintenance gefitinib than those given
      placebo.One study conducted subgroup analysis and showed that gefitinib improved
      overall survival over placebo in the second-line setting in patients of Asian
      ethnicity. All other studies did not detect any benefit on overall survival. The
      data analysed in this review were very heterogenous. We were limited in the
      amount of data that could be pooled, largely due to variations in study design.
      The risk of bias in most studies was moderate, with some studies not adequately
      addressing potential selection, attrition and reporting bias. This heterogeneity
      may have an impact on the applicability of the resultsCombining gefitinib with
      chemotherapy appears to be superior in improving progression-free survival to
      either gefitinib or chemotherapy alone, however further data and phase III
      studies in these settings are required.Gefitinib has a favourable toxicity
      profile when compared with current chemotherapy regimens. Although there is no
      improvement in overall survival, gefitinib compares favourably with cytotoxic
      chemotherapy in patients with EGFR mutations with a prolongation of progression
      free survival and a lesser side effect profile.

PMID- 29336010
TI  - The unique role of executive function skills in predicting Hong Kong
      kindergarteners' reading comprehension.
AB  - BACKGROUND: Word reading and linguistic comprehension skills are two crucial
      components in reading comprehension, according to the Simple View of Reading
      (SVR). Some researchers have posited that a third component should be involved in
      reading and understanding texts, namely executive function (EF) skills. AIM: This
      study was novel in two ways. Not only did we tested EF skills as a predictor of
      reading comprehension in a non-alphabetic language (i.e., Chinese) to extend the
      theoretical model of SVR, we also examined reading comprehension further in
      kindergarten children (age 5) in Hong Kong, in the attempt to reveal possible
      early precursors of reading comprehension. SAMPLE(S): A group of 170 K3
      kindergarteners was recruited in Hong Kong. METHODS: Children's word reading was
      assessed. Their linguistic comprehension was assessed with phonological
      awareness, verbal short-term memory, and vocabulary knowledge. Using a structured
      observation task, Head-Toes-Knees-Shoulders (HTKS), we measured their composite
      scores for EF skills. RESULTS: Head-Toes-Knees-Shoulders performance predicted
      unique variance in children's Chinese reading comprehension concurrently beyond
      word reading and a set of linguistic comprehension skills. CONCLUSIONS: The
      results highlight the important role of EF skills in beginning readers' reading
      comprehension.

PMID- 29336011
TI  - Decreased retinal sensitivity in depressive disorder: a controlled study.
AB  - OBJECTIVE: To compare pupil responses in depressed patients with a seasonal
      pattern, depressed patients without a seasonal pattern and healthy controls as a
      function of daylight hours on the testing day. METHOD: Patients suffering from a
      major depressive episode were included in wintertime. The pupil light reflex was
      measured at inclusion and in the following summer using a binocular pupillometer.
      A protocol of low (1 lux) and high (400 lux) intensity red and blue lights was
      used to assess rod, cone and melanopsin-containing intrinsic photosensitive
      retinal ganglion cell input to the pupil reflex. RESULTS: The mean group pupil
      responses associated with a melanopsin-mediated sustained pupil response at 400
      lux blue light were significantly reduced in the depressed subjects (N = 39) as
      compared to the healthy controls (N = 24) (P = 0.023). Across all groups, a
      reduction in number of daylight hours was significantly associated with a
      reduction in sustained pupil response (P = 0.007). All groups showed an equal
      effect of daylight hours on the melanopsin-mediated sustained pupil response.
      CONCLUSION: The melanopsin-mediated sustained pupil contraction to offset of high
      intensity blue light is reduced in depressed patients. These results further
      emphasize the interaction of light exposure with depression.

PMID- 29336012
TI  - Predictors and consequences of health anxiety symptoms: a novel twin modeling
      study.
AB  - OBJECTIVE: The question of how to best conceptualize health anxiety (HA) from a
      diagnostic and etiological perspective remains debated. The aim was to examine
      the relationship between HA and the symptoms of anxiety and obsessive-compulsive
      related disorders in a normative twin population. METHOD: Four hundred and ninety
      six monozygotic adult twin pairs from the Australian Twin Registry participated
      in the study (age, 34.4 +/- 7.72 years; 59% females). Validated scales were used
      to assess each domain. We applied a twin regression methodology-ICE FALCON-to
      determine whether there was evidence consistent with 'causal' relationships
      between HA and other symptoms by fitting and comparing model estimates. RESULTS:
      Estimates were consistent with higher levels of obsessing ('unwanted thoughts')
      (P = 0.008), social anxiety (P = 0.03), and body dysmorphic symptoms (P = 0.008)
      causing higher levels of HA symptoms, and with higher levels of HA symptoms
      causing higher levels of physical/somatic anxiety symptoms (P = 0.001).
      CONCLUSION: Obsessional thoughts, body dysmorphic concerns, and social anxiety
      symptoms may have a causal influence on HA. To report physical/somatic anxiety
      appears to be a consequence of the underlying presence of HA-related fears.
      Should our results be confirmed by longitudinal studies, the evaluation and
      treatment of HA may benefit from the consideration of these identified risk
      factors.

PMID- 29336013
TI  - Systematic review of atopic dermatitis disease definition in studies using
      routinely collected health data.
AB  - BACKGROUND: Routinely collected electronic health data obtained for
      administrative and clinical purposes are increasingly used to study atopic
      dermatitis (AD). Methods for identifying AD patients in routinely collected
      electronic health data differ, and it is unknown how this might affect study
      results. OBJECTIVES: To evaluate how patients with AD have been identified in
      studies using routinely collected electronic health data, to determine whether
      these methods were validated and to estimate how the method for identifying
      patients with AD affected variability in prevalence estimates. METHODS: We
      systematically searched PubMed, Embase and Web of Science for studies using
      routinely collected electronic health data that reported on AD as a primary
      outcome. Studies of localized AD and other types of dermatitis were excluded. The
      protocol for this review was registered in PROSPERO (CRD42016037968). RESULTS: In
      total, 59 studies met eligibility criteria. Medical diagnosis codes for inclusion
      and exclusion, number of occasions of a code, type of provider associated with a
      code and prescription data were used to identify patients with AD. Only two
      studies described validation of their methods and no study reported on disease
      severity. Prevalence estimates ranged from 0.18% to 38.33% (median 4.91%) and up
      to threefold variation in prevalence was introduced by differences in the method
      for identifying patients with AD. CONCLUSIONS: This systematic review highlights
      the need for clear reporting of methods for identifying patients with AD in
      routinely collected electronic health data to allow for meaningful interpretation
      and comparison of results.

PMID- 29336014
TI  - Response to: Yazdani A. Surgery or in vitro fertilisation: The simplicity of this
      question belies its complexity. When all you have is a hammer, everything looks
      like a nail.
AB  - This is perhaps the most apt mantra of IVF (in vitro fertilisation) as a
      treatment in Australasia in this day and age. It is also important to note the
      truth in the identification of IVF being low skill-based, largely independent of
      the practitioner, but more importantly costly, and with few exceptions, only
      available in the private sector. Such revelations really require a rethink of the
      entire reproductive endocrinology and infertility (CREI) subspecialty. In fact,
      if there is only one solution to all fertility problems - that of the 'effective
      IVF procedure' - why not do away completely with the clinician and simply have
      nurse practitioners who oversee the identified issue of an individual or couple
      wanting a pregnancy? This in conjunction with the outstanding scientific advances
      that led to the initiation and promulgation of IVF really would reduce costs by
      cutting out the unnecessary clinician middle-person who is unimportant in the
      equation. It may be that such cost reduction, the disbandment of the irrelevant
      subspecialty and protocol-driven, high-quality fertility checklists would allow
      this to be a publically accessible service for all, not just those who can afford
      it.

PMID- 29336015
TI  - A Metatheory for Cognitive Development (or "Piaget is Dead" Revisited).
AB  - In 1997, I argued that with the loss of Piaget's theory as an overarching guide,
      cognitive development had become disjointed and a new metatheory was needed to
      unify the field. I suggested developmental biology, particularly evolutionary
      theory, as a candidate. Here, I examine the increasing emphasis of biology in
      cognitive development research over the past 2 decades. I describe briefly the
      emergence of evolutionary developmental psychology and examine areas in which
      proximal and distal biological causation have been particularly influential. I
      argue that developmental biology will continue to increasingly influence research
      and theory in cognitive development and that evolutionary theory is well on its
      way to becoming a metatheory, not just for cognitive development, but for
      developmental psychology generally.

PMID- 29336016
TI  - Could conjunctivitis in patients with atopic dermatitis treated with dupilumab be
      caused by colonization with Demodex and increased interleukin-17 levels?: reply
      from the authors.

PMID- 29336018
TI  - The Legacy of Early Abuse and Neglect for Social and Academic Competence From
      Childhood to Adulthood.
AB  - This study used data from the Minnesota Longitudinal Study of Risk and Adaptation
      (N = 267) to investigate whether abuse and neglect experiences during the first 5
      years of life have fading or enduring consequences for social and academic
      competence over the next 3 decades of life. Experiencing early abuse and neglect
      was consistently associated with more interpersonal problems and lower academic
      achievement from childhood through adulthood (32-34 years). The predictive
      significance of early abuse and neglect was not attributable to the stability of
      developmental competence over time, nor to abuse and neglect occurring later in
      childhood. Early abuse and neglect had enduring associations with social (but not
      academic) competence after controlling for potential demographic confounds and
      early sensitive caregiving.

PMID- 29336017
TI  - Long-term surveillance of SUDEP in drug-resistant epilepsy patients treated with
      VNS therapy.
AB  - OBJECTIVE: Limited data are available regarding the evolution over time of the
      rate of sudden unexpected death in epilepsy patients (SUDEP) in drug-resistant
      epilepsy. The objective is to analyze a database of 40 443 patients with epilepsy
      implanted with vagus nerve stimulation (VNS) therapy in the United States (from
      1988 to 2012) and assess whether SUDEP rates decrease during the postimplantation
      follow-up period. METHODS: Patient vital status was ascertained using the Centers
      for Disease Control and Prevention's National Death Index (NDI). An expert panel
      adjudicated classification of cause of deaths as SUDEP based on NDI data and
      available narrative descriptions of deaths. We tested the hypothesis that SUDEP
      rates decrease with time using the Mann-Kendall nonparametric trend test and by
      comparing SUDEP rates of the first 2 years of follow-up (years 1-2) to longer
      follow-up (years 3-10). RESULTS: Our cohort included 277 661 person-years of
      follow-up and 3689 deaths, including 632 SUDEP. Primary analysis demonstrated a
      significant decrease in age-adjusted SUDEP rate during follow-up (S = -27 P =
      .008), with rates of 2.47/1000 for years 1-2 and 1.68/1000 for years 3-10 (rate
      ratio 0.68; 95% confidence interval [CI] 0.53-0.87; P = .002). Sensitivity
      analyses confirm these findings. SIGNIFICANCE: Our data suggest that SUDEP risk
      significantly decreases during long-term follow-up of patients with refractory
      epilepsy receiving VNS Therapy. This finding might reflect several factors,
      including the natural long-term dynamic of SUDEP rate, attrition, and the impact
      of VNS Therapy. The role of each of these factors cannot be confirmed due to the
      limitations of the study.

PMID- 29336019
TI  - Computerized planimetry to assess clinical responsiveness in a phase II
      randomized trial of topical R333 for discoid lupus erythematosus.
AB  - BACKGROUND: R333 is a topical janus kinase and spleen tyrosine kinase inhibitor
      being evaluated for discoid lupus erythematosus (DLE) treatment. There is no
      validated measure to assess the area of active DLE lesions. OBJECTIVES: To
      evaluate R333 efficacy and assess a technique to measure responsiveness. METHODS:
      Fifty-four patients with DLE were randomized in a double-blind design to R333 or
      placebo. Primary end point was the proportion of patients achieving >= 50%
      decrease in erythema and scale based on lesional Cutaneous Lupus Erythematosus
      Disease Area and Severity IndexTM for all treated lesions at week 4. Two
      dimensional (2D) area measurements for each lesion were recorded at baseline and
      weeks 1-6. Eighty-eight photographs (44 pre- and 44 post-treatment) were obtained
      from the trial and change in size of active areas was analysed by computerized
      planimetry and physician-assessed area change (PAAC). RESULTS: Thirty-six
      patients were randomized to R333 and 18 patients were randomized to placebo.
      Primary end point was not achieved. There was a strong association between lesion
      activity and physician global assessment (P < 0.001). Photos of 42 patients
      assessed by computerized planimetry demonstrated excellent inter- and intra-rater
      reliability. Area change by computerized planimetry showed a strong correlation
      with PAAC (Spearman r = 0.72). Area change by 2D measurements showed a weak
      correlation with PAAC (Spearman r = 0.29). CONCLUSIONS: Four weeks of R333
      treatment did not result in significant improvement in lesion activity. Lesion
      activity and area change using computerized planimetry are better determinants of
      responsiveness than area change using 2D measurements.

PMID- 29336021
TI  - Evolutionary Developmental Psychology: 2017 Redux.

PMID- 29336020
TI  - Return to driving after a diagnosis of epilepsy: A prospective registry study.
AB  - OBJECTIVE: To determine the frequency and predictors of return to driving within
      1 year after a diagnosis of epilepsy. METHODS: SEISMIC (the Sydney Epilepsy
      Incidence Study to Measure Illness Consequences) was a prospective, multicenter,
      community-wide study of people of all ages with newly diagnosed epilepsy in
      Sydney, Australia. Demographic, socioeconomic, and clinical characteristics and
      driving status were obtained as soon as possible after baseline registration with
      a diagnosis of epilepsy. Multivariate logistic regression was used to determine
      predictors of return to driving at 12-month follow-up. RESULTS: Among 181 (76%)
      adult participants (>=18 years old) who reported driving before an epilepsy
      diagnosis, 152 provided information on driving at 12 months, of whom 118 (78%)
      had returned to driving. Driving for reasons of getting to work or place of
      education (odds ratio [OR] = 4.70, 95% confidence intervals [CI] = 1.87-11.86),
      no seizure recurrence (OR = 5.15, 95% CI = 2.07-12.82), and being on no or a
      single antiepileptic drug (OR = 4.54, 95% CI = 1.45-14.22) were associated with
      return to driving (C statistic = 0.79). More than half of participants with
      recurrent seizures were driving at follow-up. SIGNIFICANCE: Early return to
      driving after a diagnosis of epilepsy is related to work/social imperatives and
      control of seizures, but many people with recurrent seizures continue to drive.
      Further efforts are required to implement driving restriction policies and to
      provide transport options for people with epilepsy.

PMID- 29336022
TI  - Nonspecific diffuse alopecia as a single manifestation of syphilis infection:
      clinical and trichoscopic features.

PMID- 29336023
TI  - Bridging Evolutionary Biology and Developmental Psychology: Toward An Enduring
      Theoretical Infrastructure.
AB  - Bjorklund synthesizes promising research directions in developmental psychology
      using an evolutionary framework. In general terms, we agree with Bjorklund:
      Evolutionary theory has the potential to serve as a metatheory for developmental
      psychology. However, as currently used in psychology, evolutionary theory is far
      from reaching this potential. In evolutionary biology, formal mathematical models
      are the norm. In developmental psychology, verbal models are the norm. In order
      to reach its potential, evolutionary developmental psychology needs to embrace
      formal modeling.

PMID- 29336025
TI  - How Children Invented Humanity.
AB  - I use the commentaries of Legare, Clegg, and Wen and of Frankenhuis and Tiokhin
      as jumping-off points to discuss an issue hinted at both in my essay and their
      commentaries: How a developmental perspective can help us achieve a better
      understanding of evolution. I examine briefly how neoteny may have contributed to
      human morphology; how developmental plasticity in great apes, and presumably our
      common ancestor with them, may have led the way to advances in social cognition;
      and how the "invention" of childhood contributed to unique human cognitive
      abilities. I conclude by acknowledging that not all developmentalists have
      adopted an evolutionary perspective, but that we are approaching a time when an
      evolutionary perspective will be implicit in the thinking of all psychologists.

PMID- 29336024
TI  - Facility and State Variation in Hip Fracture in U.S. Nursing Home Residents.
AB  - OBJECTIVES: To quantify the variation in hip fracture incidence across U.S.
      nursing home (NH) facilities and states and examine how hip fracture incidence
      varies according to facility- and state-level characteristics. DESIGN:
      Retrospective cohort using linked national Minimum Data Set assessments; Online
      Survey, Certification and Reporting records; and Medicare claims. SETTING: U.S.
      NHs with 100 or more beds. PARTICIPANTS: Long-stay NH residents between May 1,
      2007, and April 30, 2008, from 1,481 facilities and 46 U.S. states (N = 201,892).
      MEASUREMENTS: Incident hip fractures were ascertained using Medicare Part A
      diagnostic codes. Each resident was followed for up to 2 years. RESULTS: The mean
      adjusted incidence rate of hip fractures for all facilities was 3.13 (95%
      confidence interval (CI) = 3.01-3.26) per 100 person-years (range 1.20, 95% CI =
      1.15-1.26 to 6.40, 95% CI = 6.07-6.77). Facilities with the highest rates of hip
      fracture had greater percentages of residents taking psychoactive medications
      (top tertile 27.2%, bottom tertile 24.8%), and fewer nursing (top tertile 3.43,
      bottom tertile 3.53) and direct care (top tertile 3.22, bottom tertile 3.29)
      hours per day per resident. The combination of state and facility characteristics
      explained 6.7% of the variation in hip fracture, and resident characteristics
      explained 7.6%. CONCLUSION: Much of the variation in hip fracture incidence
      remained unexplained, although these findings indicate that potentially
      modifiable state and facility characteristics such as psychoactive drug
      prescribing and minimum staffing requirements could be addressed to help reduce
      the rate of hip fracture in U.S. NHs.

PMID- 29336026
TI  - Youth's Conceptions of Adolescence Predict Longitudinal Changes in Prefrontal
      Cortex Activation and Risk Taking During Adolescence.
AB  - The development of cognitive control during adolescence is paralleled by changes
      in the function of the lateral prefrontal cortex (PFC). Using a three-wave
      longitudinal neuroimaging design (N = 22, Mage  = 13.08 years at Wave 1), this
      study examined if youth's stereotypes about teens modulate changes in their
      neural activation during cognitive control. Participants holding stereotypes of
      teens as irresponsible in the family context (i.e., ignoring family obligations)
      in middle school showed increases in bilateral ventrolateral PFC activation
      during cognitive control over the transition to high school, which was associated
      with increases in risk taking. These findings provide preliminary evidence that
      youth's conceptions of adolescence play a role in neural plasticity over this
      phase of development.

PMID- 29336027
TI  - Evaluating the validity of subclassifying warfarin-associated nonuremic
      calciphylaxis: a retrospective cohort study.
AB  - BACKGROUND: Calciphylaxis is a devastating multifactorial disorder of the
      subcutaneous fat that is known to be associated with hypercoagulability. Recent
      literature has proposed subclassifying patients with calciphylaxis as having
      warfarin-associated or warfarin-unassociated disease. AIM: We aimed to determine
      whether patients with warfarin-associated calciphylaxis differ clinically from
      patients with warfarin-unassociated calciphylaxis. MATERIALS AND METHODS: We
      performed a subgroup analysis of patients with nonuremic calciphylaxis from a
      previously studied cohort and compared clinical and outcomes features of patients
      who were taking warfarin at the time of disease onset to those of patients who
      were not. RESULTS: Nineteen patients with nonuremic calciphylaxis were
      identified, including 10 (53%) who had been on warfarin at the time of disease
      onset and 9 (47%) who had not. Of all clinical and outcomes parameters tested, no
      significant differences were detected between the two groups. DISCUSSION AND
      CONCLUSIONS: Though this study is limited by its retrospective nature and the
      relatively small number of patients studied, available data do not support
      subclassifying patients with nonuremic calciphylaxis as having warfarin
      associated or warfarin-unassociated disease. Rather, the body of literature would
      suggest that identification and correction of underlying disorders of
      hypercoagulability should be prioritized.

PMID- 29336028
TI  - The role of the head in configural body processing: Behavioural and
      electrophysiological evidence from the inversion and scrambling effect.
AB  - The present study aimed to further explore the role of the head for configural
      body processing by comparing complete bodies with headless bodies and faceless
      heads (Experiment 1). A second aim was to further explore the role of the eye
      region in configural face processing (Experiment 2). Due to that, we conducted a
      second experiment with complete faces, eyeless faces, and eyes. In addition, we
      used two effects to manipulate configural processing: the effect of stimulus
      inversion and scrambling. The current data clearly show an inversion effect for
      intact bodies presented with head and faces including the eye region. Thus, the
      head and the eye region seem to be central for configural processes that are
      manipulated by the effect of stimulus inversion. Furthermore, the behavioural and
      electrophysiological body inversion effect depends on the intact configuration of
      bodies and is associated with the N170 as the face inversion effect depends on
      the intact face configuration. Hence, configural body processing depends not only
      on the presence of the head but rather on a complete representation of human
      bodies that includes the body and the head. Furthermore, configural face
      processing relies on intact and complete face representations that include faces
      and eyes.

PMID- 29336029
TI  - Sudden unexpected death in epilepsy in patients treated with brain-responsive
      neurostimulation.
AB  - OBJECTIVE: To study the incidence and clinical features of sudden unexpected
      death in epilepsy (SUDEP) in patients treated with direct brain-responsive
      stimulation with the RNS System. METHODS: All deaths in patients treated in
      clinical trials (N = 256) or following U.S. Food and Drug Administration (FDA)
      approval (N = 451) through May 5, 2016, were adjudicated for SUDEP. RESULTS:
      There were 14 deaths among 707 patients (2208 postimplantation years), including
      2 possible, 1 probable, and 4 definite SUDEP events. The rate of probable or
      definite SUDEP was 2.0/1000 (95% confidence interval [CI] 0.7-5.2) over 2036
      patient stimulation years and 2.3/1000 (95% CI 0.9-5.4) over 2208 patient implant
      years. Stored electrocorticograms around the time of death were available for 4
      patients with probable/definite SUDEP and revealed the following: frequent
      epileptiform activity ending abruptly (n = 2), no epileptiform activity or
      seizures (n = 1), and an electrographic and witnessed seizure with cessation of
      postictal electrocorticography (ECoG) activity associated with apnea and
      pulselessness (n = 1). SIGNIFICANCE: The SUDEP rate of 2.0/1000 patient
      stimulation years among patients treated with the RNS System is favorable
      relative to treatment-resistant epilepsy patients randomized to the placebo arm
      of add-on drug studies or with seizures after resective surgery. Our findings
      support that treatments that reduce seizures reduce SUDEP risk and that not all
      SUDEPs follow seizures.

PMID- 29336030
TI  - The aryl hydrocarbon receptor modulates the function of human CD56bright NK
      cells.
AB  - Human natural killer (NK) cells are divided into two subsets: CD56bright and
      CD56dim NK cells, which differ in maturation, function and distribution.
      Mechanisms regulating NK cell functions are not completely understood. Aryl
      hydrocarbon receptor (AhR) is a ligand-activated transcription factor, that binds
      to a variety of endogenous and exogenous molecules, and that has recently been
      shown to modulate the function and differentiation of immune cells. Here, we
      studied the expression of AhR and its involvement in the regulation of NK cell
      functions. We found that AhR mRNA is highly expressed in peripheral CD56bright NK
      cells and that AhR mRNA expression gradually decreases as NK cells display a more
      mature phenotype. CD56bright NK cells were highly sensitive to AhR ligands.
      Specifically, AhR ligands modulated their activation and their expression of NK
      cell receptors, as well as cytokine secretion which is the major function of
      these cells. As CD56bright NK cells are highly enriched in tissues and in tumors,
      our observations point to a possible effect of local AhR ligands in the
      regulation of the function of CD56bright tissue-resident or intratumoral NK
      cells.

PMID- 29336032
TI  - My mind, your mind, and God's mind: How children and adults conceive of different
      agents' moral beliefs.
AB  - Extending prior research on belief attributions, we investigated the extent to
      which 5- to 8-year-olds and adults distinguish their beliefs and other humans'
      beliefs from God's beliefs. In Study 1, children reported that all agents held
      the same beliefs, whereas adults drew greater distinctions among agents. For
      example, adults reported that God was less likely than humans to view behaviors
      as morally acceptable. Study 2 additionally investigated attributions of beliefs
      about controversial behaviours (e.g., telling prosocial lies) and belief
      stability. These data replicated the main results from Study 1 and additionally
      revealed that adults (but not children) reported that God was less likely than
      any other agent to think that controversial behaviours were morally acceptable.
      Furthermore, across ages, participants reported that another person's beliefs
      were more likely to change than either God's beliefs or their own beliefs. We
      discuss implications for theories regarding belief attributions and for religious
      and moral cognition. Statement of contribution What is already known on this
      subject Preschoolers can attribute different beliefs to different humans Children
      and adults attribute greater cognitive capacities to God than to humans What the
      present study adds Children attribute the same moral beliefs to God and humans
      Adults distinguish among different agents' minds when attributing moral beliefs
      Developmental differences are less pronounced in judgements of belief stability.

PMID- 29336031
TI  - Experiences of case management with chronic illnesses: a qualitative systematic
      review.
AB  - AIM: This qualitative systematic review aimed to identify and synthesize recent
      qualitative studies to improve understanding of the experiences and perceptions
      of case management interventions that individuals with chronic illnesses and
      their caregivers have. BACKGROUND/INTRODUCTION: Case management has been shown to
      be effective at improving quality of care and lowering costs for individuals with
      chronic illnesses. However, no qualitative review has been synthesized with
      recent qualitative studies about case management experiences by individual with
      chronic illnesses. METHODS: This qualitative systematic review uses a thematic
      synthesis method to review 10 qualitative studies published within the last 10
      years, from 2007 to 2016, thereby identifying and discussing the understandings
      that individuals with chronic illnesses and their caregivers have about case
      management. RESULTS: From this synthesis, three themes were identified as
      facilitators of case management (access to healthcare resources, health status
      supports and emotional aid) and two themes were identified as barriers to it (low
      information about case management and time constraints). CONCLUSIONS: This is the
      first qualitative systematic review of the perceptions and experiences that
      individuals with chronic illnesses and their caregivers have about case
      management. The facilitators of case management can be employed to inform
      patients about the benefits of case management and to improve population health.
      IMPLICATIONS FOR NURSING AND HEALTH POLICY: The findings about barriers to case
      management can be used to reform case management for populations with chronic
      illnesses. These factors should be considered by nursing researchers and
      healthcare policymakers when implementing case management.

PMID- 29336033
TI  - H2 O2 mediates nitrate-induced iron chlorosis by regulating iron homeostasis in
      rice.
AB  - The uptake of nitrate by plant roots causes a pH increment in rhizosphere and
      leads to iron (Fe) deficiency in rice. However, little is known about the
      mechanism how the nitrate uptake-induced high rhizosphere pH causes Fe
      deficiency. Here, we found that rice showed severe leaf chlorosis and large
      amounts of Fe plaque were aggregated on the root surface and intercellular space
      outside the exodermis in a form of ferrihydrite under alkaline conditions. In
      this case, there was significantly decreased Fe concentration in shoots, and the
      Fe deficiency responsive genes were strongly induced in the roots. The high
      rhizosphere pH induced excess hydrogen peroxide (H2 O2 ) production in the
      epidermis due to the increasing expression of NADPH-oxidase respiratory burst
      oxidase homolog 1, which enhanced root oxidation ability and improved the Fe
      plaque formation in rhizosphere. Further, the concentrated H2 O2 regulated the
      phenylpropanoid metabolism with increased lignin biosynthesis and decreased
      phenolics secretion, which blocked apoplast Fe mobilization efficiency. These
      factors coordinately repressed the Fe utilization in rhizosphere and led to Fe
      deficiency in rice under high pH. In conclusion, our results demonstrate that
      nitrate uptake-induced rhizosphere alkalization led to Fe deficiency in rice,
      through H2 O2 -dependent manners of root oxidation ability and phenylpropanoid
      metabolism.

PMID- 29336035
TI  - Jim's View: "Some Thoughts for Young Scientists".

PMID- 29336034
TI  - Quantitative evaluation of collagen and elastic fibers after intense pulsed light
      treatment of mouse skin.
AB  - BACKGROUND AND OBJECTIVE: The aging of human skin includes intrinsic aging and
      photo-aging, which are characterized by a decrease in collagen and the deposition
      of abnormal elastic fibers. Intense pulsed light (IPL) sources are widely used in
      medicine to treat various cosmetic problems, including photo-damaged skin. Few
      studies have examined the microscopic changes produced by IPL. The objective of
      this study was to quantitatively evaluate the effects of IPL on collagen and
      elastic fibers in mice. MATERIALS AND METHODS: Forty female BALB/c mice were
      divided into four subgroups. Group 1 was the control group (n = 10), and groups
      2, 3, and 4 were treatment groups (n = 10 in each group). Group 2 received one
      treatment, group 3 received two treatments, and group 4 received three treatments
      every 2 weeks. Skin tissue was obtained from irradiated areas 24 hours after the
      last treatment in each mouse. Collagen fibers were identified using the
      picrosirius red method. Elastic fibers were marked by Weigert-oxone stain. All
      samples were analyzed and quantified by a light microscope using analyzer system
      images. RESULTS: Group 4, which received three IPL treatments, showed significant
      quantitative increases in both collagen fibers (P < 0.05) and elastic fibers (P <
      0.01). Collagen fibers demonstrated a better parallel distribution in relation to
      the epidermis. CONCLUSION: IPL treatment significantly increased the number of
      collagen and elastic fibers within the dermis and improved the parallel
      distribution of collagen fibers in relation to the epidermis. These results were
      evident after three IPL treatments. Lasers Surg. Med. (c) 2018 Wiley Periodicals,
      Inc.

PMID- 29336037
TI  - Developmental control of hypoxia during bud burst in grapevine.
AB  - Dormant or quiescent buds of woody perennials are often dense and in the case of
      grapevine (Vitis vinifera L.) have a low tissue oxygen status. The precise timing
      of the decision to resume growth is difficult to predict, but once committed, the
      increase in tissue oxygen status is rapid and developmentally regulated. Here, we
      show that more than a third of the grapevine homologues of widely conserved
      hypoxia-responsive genes and nearly a fifth of all grapevine genes possessing a
      plant hypoxia-responsive promoter element were differentially regulated during
      bud burst, in apparent harmony with resumption of meristem identity and cell
      cycle gene regulation. We then investigated the molecular and biochemical
      properties of the grapevine ERF-VII homologues, which in other species are oxygen
      labile and function in transcriptional regulation of hypoxia-responsive genes.
      Each of the 3 VvERF-VIIs were substrates for oxygen-dependent proteolysis in
      vitro, as a function of the N-terminal cysteine. Collectively, these data support
      an important developmental function of oxygen-dependent signalling in determining
      the timing and effective coordination bud burst in grapevine. In addition, novel
      regulators, including GASA-, TCP-, MYB3R-, PLT-, and WUS-like transcription
      factors, were identified as hallmarks of the orderly and functional resumption of
      growth following quiescence in buds.

PMID- 29336036
TI  - The incidence and significance of periictal apnea in epileptic seizures.
AB  - OBJECTIVE: The aim of this study was to investigate periictal central apnea as a
      seizure semiological feature, its localizing value, and possible relationship
      with sudden unexpected death in epilepsy (SUDEP) pathomechanisms. METHODS: We
      prospectively studied polygraphic physiological responses, including inductance
      plethysmography, peripheral capillary oxygen saturation (SpO2 ),
      electrocardiography, and video electroencephalography (VEEG) in 473 patients in a
      multicenter study of SUDEP. Seizures were classified according to the
      International League Against Epilepsy (ILAE) 2017 seizure classification based on
      the most prominent clinical signs during VEEG. The putative epileptogenic zone
      was defined based on clinical history, seizure semiology, neuroimaging, and EEG.
      RESULTS: Complete datasets were available in 126 patients in 312 seizures. Ictal
      central apnea (ICA) occurred exclusively in focal epilepsy (51/109 patients [47%]
      and 103/312 seizures [36.5%]) (P < .001). ICA was the only clinical manifestation
      in 16/103 (16.5%) seizures, and preceded EEG seizure onset by 8 +/- 4.9 s, in
      56/103 (54.3%) seizures. ICA >=60 s was associated with severe hypoxemia (SpO2
      <75%). Focal onset impaired awareness (FOIA) motor onset with automatisms and FOA
      nonmotor onset semiologies were associated with ICA presence (P < .001), ICA
      duration (P = .002), and moderate/severe hypoxemia (P = .04). Temporal lobe
      epilepsy was highly associated with ICA in comparison to extratemporal epilepsy
      (P = .001) and frontal lobe epilepsy (P = .001). Isolated postictal central apnea
      was not seen; in 3/103 seizures (3%), ICA persisted into the postictal period.
      SIGNIFICANCE: ICA is a frequent, self-limiting semiological feature of focal
      epilepsy, often starting before surface EEG onset, and may be the only clinical
      manifestation of focal seizures. However, prolonged ICA (>=60 s) is associated
      with severe hypoxemia and may be a potential SUDEP biomarker. ICA is more
      frequently seen in temporal than extratemporal seizures, and in typical temporal
      seizure semiologies. ICA rarely persists after seizure end. ICA agnosia is
      typical, and thus it may remain unrecognized without polygraphic measurements
      that include breathing parameters.

PMID- 29336038
TI  - A single-nucleotide polymorphism in the canine cytochrome b5 reductase (CYB5R3)
      gene is associated with sulfonamide hypersensitivity and is overrepresented in
      Doberman Pinschers.
AB  - Canine sulfonamide hypersensitivity (HS) has been associated with a variant in
      the cytochrome b5 reductase gene (CYB5R3 729A>G), which encodes a drug
      detoxifying enzyme. Study objectives were to determine variant allele frequency
      in Doberman Pinschers (DOBE), a breed which may be predisposed to sulfonamide HS,
      and to characterize the effects of CYB5R3 729G on gene expression and function.
      CYB5R3 729A>G allele frequencies were compared between DOBE (n = 24) vs. non
      Doberman (non-DOBE; n = 60) dogs. CYB5R3mRNA expression, protein expression, and
      reduction of sulfamethoxazole hydroxylamine were compared between banked canine
      liver samples of 729AA vs. GG genotype. The 729G allele was overrepresented in
      DOBE (1.00) vs. non-DOBE dogs (0.567, p < .0001). mRNA and protein expressions as
      well as cyt b5 reductase activity were similar between livers of AA and GG
      genotype. All Doberman Pinschers in this study were homozygous for CYB5R3 729G,
      which could contribute to this breed's apparent predisposition to sulfonamide HS.
      However, CYB5R3 729G does not alter sulfamethoxazole detoxification capacity, so
      a direct role could not be demonstrated. It is possible that this marker is
      linked to another contributing variant.

PMID- 29336039
TI  - Pollen germination and in vivo fertilization in response to high-temperature
      during flowering in hybrid and inbred rice.
AB  - High-temperature during flowering in rice causes spikelet sterility and is a
      major threat to rice productivity in tropical and subtropical regions, where
      hybrid rice development is increasingly contributing to sustain food security.
      However, the sensitivity of hybrids to increasing temperature and physiological
      responses in terms of dynamic fertilization processes is unknown. To address
      these questions, several promising hybrids and inbreds were exposed to control
      temperature and high day-time temperature (HDT) in Experiment 1, and hybrids
      having contrasting heat tolerance were selected for Experiment 2 for further
      physiological investigation under HDT and high-night-time-temperature treatments.
      The day-time temperature played a dominant role in determining spikelet fertility
      compared with the night-time temperature. HDT significantly induced spikelet
      sterility in tested hybrids, and hybrids had higher heat susceptibility than the
      high-yielding inbred varieties. Poor pollen germination was strongly associated
      with sterility under high-temperature. Our novel observations capturing the
      series of dynamic fertilization processes demonstrated that pollen tubes not
      reaching the viable embryo sac was the major cause for spikelet sterility under
      heat exposure. Our findings highlight the urgent need to improve heat tolerance
      in hybrids and incorporating early-morning flowering as a promising trait for
      mitigating HDT stress impact at flowering.

PMID- 29336040
TI  - Evaluation of reference values of standard semen parameters in fertile Egyptian
      men.
AB  - The reference values of human semen, published in the WHO's latest edition in
      2010, were lower than those previously reported. The objective of this study was
      to evaluate reference values of standard semen parameters in fertile Egyptian
      men. This cross-sectional study included 240 fertile men. Men were considered
      fertile when their wives had recent spontaneous pregnancies with time to
      pregnancy (TTP) <=12 months. The mean age of fertile men was 33.8 +/- 0.5 years
      (range 20-55 years). The 5th percentiles (95% confidence interval) of macroscopic
      semen parameters were 1.5 ml for volume and 7.2 for pH. The 5th percentiles of
      microscopic parameters were 15 million/ml for sperm concentration, 30 million per
      ejaculate for total sperm count, 50% for total motility, 40% for progressive
      motility, 62% for vitality, 4% for normal sperm forms and 0.1 million/ml for
      seminal leucocyte counts. In conclusion, fertile Egyptian men had higher
      reference values of sperm total motility, progressive motility and vitality, and
      lower reference values for total sperm counts as compared to those determined by
      the latest edition of the WHO laboratory manual in 2010. Other semen parameters
      were identical to those defined by the WHO 2010 manual.

PMID- 29336041
TI  - Symptoms of social anxiety, depression, and stress in parents of children with
      social anxiety disorder.
AB  - OBJECTIVES: It has been suggested that elevated maternal social anxiety may play
      a disorder-specific role in maintaining childhood social anxiety disorder (SAD),
      but few studies have examined whether mothers of children with SAD are more
      socially anxious than mothers of children with other anxiety disorders (ANX).
      This study set out to examine whether symptoms of social anxiety were more severe
      amongst mothers of 7-12 year old children presenting for treatment with SAD (n =
      260) compared to those presenting with ANX (n = 138). In addition, we examined
      whether there were differences between these two groups in terms of maternal and
      paternal general anxiety, depression, and stress. METHOD: Parents of 7-12 year
      old children referred for treatment of SAD or ANX completed self-report
      questionnaire measures of emotional symptoms. RESULTS: Compared to mothers of
      children with ANX, mothers of children with SAD reported significantly higher
      levels of social anxiety, general anxiety, and depression. In addition, fathers
      of children with SAD reported significantly higher levels of anxiety, stress, and
      depression than fathers of children with ANX. CONCLUSIONS: This study is one of
      the few existing studies that have examined mothers' and fathers' psychopathology
      across different childhood anxiety disorders. Compared to parents of children
      with ANX, parents of children with SAD may have poorer mental health which may
      inhibit optimum child treatment outcomes for children with SAD. Thus, targeting
      parental psychopathology may be particularly important in the treatment of
      childhood SAD. PRACTITIONER POINTS: Consideration of parental psychopathology may
      be particularly important in the treatment of childhood social anxiety disorder.
      Mothers of children with social anxiety disorder are more socially anxious than
      mothers of children with other anxiety disorders Fathers of children with social
      anxiety disorder are more anxious and depressed than fathers of children with
      other anxiety disorders Participants were predominantly of high socioeconomic
      status. Parental diagnostic information was not obtained.

PMID- 29336042
TI  - Forum for the History of the Human Sciences.

PMID- 29336043
TI  - 2017 Cheiron Young Scholar Award Winner: Shayna Fox Lee.

PMID- 29336044
TI  - ESHHS 2018, GRONINGEN (NL) - First call for abstracts.

PMID- 29336045
TI  - The creation of a postcolonial subject: The Chicago and Ateneo de Manila schools
      and the Peace Corps in the Philippines, 1960-1970.
AB  - In the 1950s and 1960s scholars from the University of Chicago and the Ateneo de
      Manila created social scientific knowledge that helped establish the Peace Corps
      as a Cold War institution in the Philippines. Central were the social scientists
      at the University of Chicago and the Ateneo de Manila University who established
      a knowable postcolonial subject: "the Filipino," which resulted from their
      research on Philippine values. In this context, the Ateneo/Chicago social
      scientists developed the "SIR," the "smooth interpersonal relation" model that
      entails the notion that Filipinos and Filipinas particularly valued this
      nonconfrontational skill set among people. The SIR model was taught by social
      science experts to early Peace Corps volunteers as they prepared for their
      assignments in the Philippines. The article shows how the SIR model could cause
      distress and confusion as it was applied by Peace Corps volunteers in the
      Philippines.

PMID- 29336046
TI  - News and Notes: Conferences.

PMID- 29336047
TI  - Acrodermatitis acidaemica.
AB  - Methylmalonic acidaemia (MMA) is an inborn error of amino acid metabolism that
      may be associated with cutaneous manifestations mimicking other diagnoses,
      including staphylococcal scalded skin syndrome (SSSS), psoriasis and
      acrodermatitis enteropathica. Whether this is due to the underlying metabolic
      disorder itself or occurs as a consequence of dietary restriction has yet to be
      elucidated. Skin biopsies typically show histological features shared by a number
      of other metabolic disorders and nutritional deficiency-associated diseases. Some
      presentations, especially SSSS-like eruptions, may be associated with acute
      metabolic decompensation. An underlying metabolic disorder, such as MMA, should
      be considered in a diagnosed adult or undiagnosed child presenting with skin
      eruptions that resemble those listed above, so that specialist management may be
      initiated early.

PMID- 29336048
TI  - Fetal growth: too little or just right?

PMID- 29336049
TI  - A distinct group of north European Aedes vexans as determined by mitochondrial
      and nuclear markers.
AB  - The floodwater mosquito Aedes (Aedimorphus) vexans (Meigen, 1830) (Diptera:
      Culicidae) is common in several areas of Sweden and is predicted to become more
      abundant in the wake of expected changes in precipitation and temperature caused
      by climate change. As well as being a nuisance, Ae. vexans can act as a vector of
      over 30 viruses. In the event of an outbreak of disease caused by a vector-borne
      virus, knowledge of the distribution, population structure and intermixing of
      populations from different locations will help direct resources to target
      locations to prevent spread of the pathogen. The present study analysed
      individual Ae. vexans from eight locations throughout Sweden. Based on the
      mitochondrial cytochrome oxidase I (COI) marker, a subset of the analysed
      mosquitoes cluster apart from the other samples. Similarly, two nuclear loci were
      sequenced and the same phylogenetic structure observed. These results indicate
      that this group represents a reproductively isolated population among Ae. vexans.
      Comparisons with COI sequences held in the Barcode of Life Database (BoLD) for
      Ae. vexans from around the world show that specimens collected in Belgium and
      Estonia group together with the Swedish group, suggesting that this genotype is
      present throughout northern Europe. These results suggest there is a cryptic
      taxonomic unit related to Ae. vexans in northern Europe.

PMID- 29336050
TI  - Sperm fluorescent in situ hybridisation study of interchromosomal effect in six
      Tunisian carriers of reciprocal and Robertsonian translocations.
AB  - Carriers of structural chromosomal anomalies, translocations and inversions are
      at increased risk of aneuploid gametes production. Besides the direct effect on
      the involved chromosomes, these rearrangements might disturb the segregation of
      other structurally normal chromosomes during meiosis. Such event is known as
      interchromosomal effect. In this study, six male carriers of translocations, four
      reciprocals and two Robertsonians, were investigated. In addition, seven fertile
      men with normal 46,XY karyotypes and normal sperm characteristics were enrolled
      as a control group. Spermatic fluorescent in situ hybridisation specific for
      chromosomes X, Y, 18, 21 and 22 was carried out. The Mann-Whitney U-test was used
      to compare the aneuploidy rates between patients and controls. All translocation
      carriers showed significantly increased frequencies of disomy of all investigated
      chromosomes, and diploid gametes compared with the control group (p < .05).
      However, disomy XY was not significantly different between controls and patients
      (p > .05). We have also observed a considerable interindividual variability in
      disomy and diploidy rates. These results confirm that the interchromosomal effect
      seems to exist and could contribute to higher rates of abnormal prenatal
      aneuploidy, resulting in a small increase in the risk of miscarriage and birth of
      children with congenital abnormalities and a potential reduction in fertility.

PMID- 29336051
TI  - Right testicular volume is a dominant predictor of testicular function determined
      by sperm parameters and total testosterone.
AB  - This study aims to evaluate the predictive value of left testicular volume (LTV)
      and right testicular volume (RTV) for testicular function respectively. Men who
      requested fertility testing for any reason were enrolled from December 2012 to
      November 2015. Subjects with primary scrotal diseases or a condition interfering
      reproductive system were excluded. Testicular volume (TV) was evaluated by
      scrotal ultrasound. Sex hormone and semen analysis including sperm concentration
      (SC) and sperm motility rate (SMR) were performed. Statistical analysis including
      comparison, stepwise linear regression and logistic regression was used. Two
      hundred and seventy-four patients with oligoasthenozoospermia/low testosterone
      and 27 control subjects were enrolled. Both LTV and RTV positively correlated
      with testicular function, and no differences were found between bilateral TV. RTV
      is the best independent factor associated with testicular function determined by
      SC (beta=.292, p < .001), SMR (beta=.227, p < .001) and total testosterone (TT)
      (beta=.245, p < .001). Using a RTV value of 15.47 ml, the highest discriminating
      sensitivity and specificity were 66.7% and 62.4% respectively. RTV (<15 ml) was
      the only positive predictor for low testicular function (odds ratio=2.79, 95%
      confidence interval: 1.18-6.66; p =.020). RTV rather than LTV is the independent
      factor of overall testicular function determined by semen quality and TT levels.
      Further studies are needed to support and elucidate the difference in volume
      function between bilateral testes.

PMID- 29336052
TI  - Rapidly developing heart failure from capecitabine cardiotoxicity: a case study.

PMID- 29336053
TI  - Specific Modulation of Vertebral Marrow Adipose Tissue by Physical Activity.
AB  - Marrow adipose tissue (MAT) accumulation with normal aging impacts the bone,
      hemopoiesis, and metabolic pathways. We investigated whether exercise was
      associated with lower MAT, as measured by vertebral marrow fat fraction (VFF) on
      magnetic resonance imaging. A total of 101 healthy individuals (54 females) aged
      25 to 35 years without spine or bone disease but with distinct exercise histories
      were studied. Long-distance runners (67 km/wk, n = 25) exhibited lower mean
      lumbar VFF (27.9% [8.6%] versus 33.5% [6.0%]; p = 0.0048) than non-sporting
      referents (n = 24). In habitual joggers (28 km/wk, n = 30), mean lumbar VFF was
      31.3% (9.0%) (p = 0.22 versus referents) and 6.0 percentage points lower than
      referents at vertebrae T10 , T11 , and T12 (p <= 0.023). High-volume road cycling
      (275 km/wk, n = 22) did not impact VFF. 3D accelerations corresponding to faster
      walking, slow jogging, and high-impact activities correlated with lower VFF,
      whereas low-impact activities and sedentary time correlated with higher mean
      lumbar VFF (all p <= 0.05). Given an estimated adipose bone marrow conversion of
      7% per decade of life, long distance runners, with 5.6 percentage points lower
      VFF, showed an estimated 8-year younger vertebral marrow adipose tissue
      phenotype. Regression analysis showed a 0.7 percentage point reduction in mean
      lumbar VFF with every 9.4 km/wk run (p = 0.002). This study presents the first
      evidence in humans or animals that specific volumes and types of exercise may
      influence the age-determined adipose marrow conversion and result in low MAT.
      These results identify a potentially modifiable risk factor for prevalent chronic
      conditions related to bone metabolism, hemopoietic production, and other
      metabolic functions with potential global health applications. (c) 2017 American
      Society for Bone and Mineral Research.

PMID- 29336055
TI  - Intrauterine ritodrine exposure and childhood asthma: Is ritodrine a real
      culprit?

PMID- 29336054
TI  - The EAACI/GA2LEN/EDF/WAO guideline for the definition, classification, diagnosis
      and management of urticaria.
AB  - This evidence- and consensus-based guideline was developed following the methods
      recommended by Cochrane and the Grading of Recommendations Assessment,
      Development and Evaluation (GRADE) working group. The conference was held on 1
      December 2016. It is a joint initiative of the Dermatology Section of the
      European Academy of Allergology and Clinical Immunology (EAACI), the EU-founded
      network of excellence, the Global Allergy and Asthma European Network (GA2LEN),
      the European Dermatology Forum (EDF) and the World Allergy Organization (WAO)
      with the participation of 48 delegates of 42 national and international
      societies. This guideline was acknowledged and accepted by the European Union of
      Medical Specialists (UEMS). Urticaria is a frequent, mast cell-driven disease,
      presenting with wheals, angioedema, or both. The lifetime prevalence for acute
      urticaria is approximately 20%. Chronic spontaneous urticaria and other chronic
      forms of urticaria are disabling, impair quality of life and affect performance
      at work and school. This guideline covers the definition and classification of
      urticaria, taking into account the recent progress in identifying its causes,
      eliciting factors and pathomechanisms. In addition, it outlines evidence-based
      diagnostic and therapeutic approaches for the different subtypes of urticaria.

PMID- 29336056
TI  - ILEI is an important intermediate participating in the formation of TGF-beta1
      induced renal tubular EMT.
AB  - : Renal interstitial fibrosis is the most common process by which chronic kidney
      diseases progress to end-stage renal failure. Epithelial-to-mesenchymal
      transitions (EMTs) play a crucial role in the progression of renal interstitial
      fibrosis. A newly identified cytokine, interleukin-like EMT inducer (ILEI), has
      been linked to EMT in some diseases. However, the effects of ILEI on renal
      tubular EMT have not yet been well established. Here, we characterize the
      expression of ILEI in tubular EMT and describe the role and mechanism of ILEI in
      transforming growth factor beta 1 (TGF-beta1)-induced renal tubular EMT. The
      results indicate that ILEI is involved in renal tubular EMT induced by TGF-beta1,
      as overexpression of ILEI not only induces EMT of HK-2 cells independently but
      also profoundly enhances EMT in response to TGF-beta1. Supporting this finding,
      ILEI small interfering RNA was found to block the EMT of HK-2 cells induced by
      TGF-beta1. This work additionally suggests ILEI mediates TGF-beta1-dependent EMT
      via the extracellular regulated protein kinases (ERKs) and protein kinase B (Akt)
      signalling pathways. In conclusion, ILEI appears to play a crucial role in
      mediating TGF-beta1-induced EMT through the Akt and ERK pathways, which may
      provide a therapeutic target for the treatment of fibrotic kidney diseases.
      SIGNIFICANCE OF THE STUDY: There is no study reporting the effect of ILEI in
      renal EMTs. In this research, we examined the role and mechanism of ILEI in EMT
      using tubular epithelial cell; we found that ILEI participated in renal tubular
      EMT, and overexpression of ILEI can not only induce EMT of HK-2 cells
      independently but also enhance EMT in response to TGF-beta1. Meanwhile, we found
      ILEI small interfering RNA blocked the EMT induced by TGF-beta1, and ILEI
      participates in the EMT caused by TGF-beta1 via ERK and Akt signalling pathways.
      We hoped to provide new ideas in further study on the prevention and treatment of
      fibrotic kidney diseases.

PMID- 29336057
TI  - Amelioration of colitis through blocking lymphocytes entry to Peyer's patches by
      sphingosine-1-phosphate lyase inhibitor.
AB  - BACKGROUND AND AIM: Sphingosine-1-phosphate (S1P) receptor 1, a therapeutic
      target of the S1P1 agonist FTY720, plays a crucial role in lymphocyte migration
      and is expressed in several cells including naive T lymphocytes and endothelial
      cells. 2-Acetyl-4-tetrahydroxybutyl imidazole (THI), an inhibitor of S1P lyase,
      exhibits immunomodulatory activity through increasing the S1P concentration in
      the secondary lymphoid organs, but its effects on colitis remain unclear. This
      study aimed to clarify how THI affects colitis and migration of naive T
      lymphocytes in Peyer's patches (PPs). METHODS: The effect of THI on gut immunity
      was investigated by analyzing the dextran sulfate sodium (DSS)-induced murine
      colitis model, lymphocyte components in thoracic duct lymphocytes (TDLs), and
      microscopic movement of TDLs in PPs. RESULTS: 2-Acetyl-4-tetrahydroxybutyl
      imidazole ameliorated DSS-induced colitis histologically by causing a significant
      decrease in colonic lymphocyte infiltration and expression of mucosal pro
      inflammatory cytokines. THI suppressed the inflow of naive T lymphocytes into the
      thoracic duct. Microscopic observation of PPs in control animals revealed that
      many TDLs egressed to the stroma and migrated to lymph capillaries after
      attaching to the high endothelial venules (HEVs). THI or FTY720 treatment in
      recipient animals blocked lymphocyte egression from the HEVs to the stroma.
      CONCLUSIONS: This is the first study to clarify the ameliorating effects of THI
      on DSS-induced colitis. Microscopic observations demonstrated the involvement of
      HEVs in the egression of S1P-dependent gut-tropic T lymphocytes to lymph
      capillaries. This S1P lyase inhibitor might become a novel immunosuppressant for
      inflammatory bowel disease therapy by blocking infiltration of lymphocytes
      through HEVs into the stroma in PPs.

PMID- 29336058
TI  - Programming settings and recharge interval in a prospective study of a
      rechargeable sacral neuromodulation system for the treatment of overactive
      bladder.
AB  - AIMS: The RELAX-OAB study is designed to confirm the safety, efficacy, and
      technical performance of the Axonics r-SNM System, a miniaturized, rechargeable
      SNM system approved in Europe and Canada for the treatment of bladder and bowel
      dysfunction. The purpose of this article is to describe study subjects' ability
      to charge the rechargeable neurostimulator and to document their neurostimulator
      program settings and recharge interval over time. METHODS: Fifty-one OAB patients
      were implanted in a single-stage procedure. These results represent the 3-month
      charging experience for 48 subjects who completed the 3-month follow-up. Recharge
      intervals were estimated using therapy stimulation settings and subject
      experience was evaluated using questionnaires. RESULTS: Forty-seven of forty
      eight (98%) subjects were able to successfully charge their device prior to
      follow-up within 1-month post-implant. At 3-month post-implant, 98% of subjects
      were able to charge prior to their follow-up visit. Average stimulation amplitude
      across all subjects was 1.8 mA (+/-1.1 mA). A total of 69% of subjects had >=14
      day recharge intervals (time between charging) and 98% of subjects had >=7-day
      recharge interval. No charging related adverse events occurred. CONCLUSIONS:
      Study subjects were able to charge the Axonics r-SNM System and stimulation
      settings provided 2 weeks of therapy between recharging for most subjects.
      Subject satisfaction indicates that subjects are satisfied with rechargeable SNM
      therapy.

PMID- 29336059
TI  - Erratum for Ann. N.Y. Acad. Sci. Volume 1299: v-x.

PMID- 29336060
TI  - What the non-nephrologist needs to know about dialysis.
AB  - The End-Stage Renal Disease (ESRD) program now serves approximately 675,000
      individuals in the United States at a cost of $26.1 billion to the Medicare
      system. Given the size of this population, healthcare providers from all
      disciplines will deliver care to patients on dialysis. Mortality remains high
      among patients on chronic dialysis, with 42.3% surviving 5 years. As this is a
      vulnerable population, it is important in the care of ESRD patients that non
      nephrologists have a working knowledge of issues germane to dialysis. This review
      examines the physiology, mechanics, complications, and care delivery concerns of
      kidney dialysis modalities relevant to the non-nephrologist. The majority of
      patients receive in-center hemodialysis thrice weekly, with a small proportion on
      home-based therapies such as peritoneal dialysis or home hemodialysis. Inpatients
      may undergo hemodialysis or peritoneal dialysis, and in critically ill patients,
      continuous renal replacement therapies are utilized. Practical aspects of each of
      these modalities are discussed.

PMID- 29336061
TI  - Classifying High-risk Children Born Preterm.

PMID- 29336062
TI  - Time-Varying Effects of Signs and Symptoms on Pregnancy Loss <20 Weeks: Findings
      from a Preconception Prospective Cohort Study.
AB  - BACKGROUND: Although pregnancy loss affects one-third of pregnancies, the
      associated signs/symptoms have not been fully described. Given the dynamic nature
      of maternal physiologic adaptation to early pregnancy, we posited the
      relationships between signs/symptoms and subsequent loss would vary weekly.
      METHODS: In a preconception cohort with daily follow-up, pregnancies were
      ascertained by self-administered sensitive home pregnancy tests on day of
      expected menses. We evaluated the effects of weekly time-varying signs/symptoms
      (including vaginal bleeding, lower abdominal cramping, and nausea and/or
      vomiting) on pregnancy loss <20 weeks in Cox proportional hazards models and
      calculated the week-specific probability of loss by the presence/absence of each
      sign/symptom. RESULTS: Of 341 pregnancies ascertained by home pregnancy test, 95
      (28%) ended in loss. Relationships between signs/symptoms and loss varied across
      time since first positive pregnancy test. In the first week following pregnancy
      confirmation, when many losses occurred, bleeding [hazard ratio (HR) 8.7, 95%
      confidence interval (CI) 4.7, 16.0] and cramping (HR 1.8, 95% CI 1.2, 2.7) were
      associated with loss even when accompanied by nausea and/or vomiting (HR 5.2, 95%
      CI 2.6, 10.5). After the second week, new relationships emerged with nausea
      and/or vomiting inversely associated (HR range 0.6-0.3, all 95% CI upper bounds
      <1.00) and bleeding no longer associated with loss. Probabilities of loss of
      ranged from 78% (95% CI 59%, 96%) with bleeding present in week 1 to 8% (95% CI
      5%, 12%) with nausea/vomiting present in week 5. CONCLUSIONS: Relationships
      between signs/symptoms and pregnancy loss vary in early pregnancy possibly
      reflecting maternal physiologic response.

PMID- 29336063
TI  - Use of complementary and alternative medicine in children with asthma.

PMID- 29336064
TI  - Home hemodialysis education during postdoctoral training: Challenges and
      innovations.
AB  - Inadequate education in home hemodialysis (HHD) fellowship training might
      contribute to underutilization of this modality in the United States. Most
      graduates of nephrology fellowships do not grade themselves as competent in HHD
      suggesting that fellowship training in HHD is inadequate. An essential component
      for fellow education is at least one faculty member with expertise in HHD who is
      passionate about promoting the use of this modality. At a minimum, fellow
      training should utilize a curriculum that includes both lectures about HHD and
      outpatient clinical exposure to this modality over a period of at least 6-12
      months. Fellows benefit from the opportunity to transition at least three
      patients to a home modality to gain experience with modality education, access
      placement, initial prescriptions, and home dialysis training. They should spend
      time with HHD training nurses to learn more about modality education, observe
      nurse intake interviews with patients in order to learn the criteria for entrance
      into the home dialysis program as well as recognize how to identify potential
      barriers to successful home dialysis therapy. To expose fellows to problems that
      do not occur during clinic visits fellows are encouraged to take first call
      during the day for HHD patients. There are many opportunities to do research and
      quality improvement projects which might also propel some fellows into an
      academic career as a home dialysis nephrologist.

PMID- 29336065
TI  - Optimization of 18 F-syntheses using 19 F-reagents at tracer-level concentrations
      and liquid chromatography/tandem mass spectrometry analysis: Improved synthesis
      of [18 F]MDL100907.
AB  - Traditional radiosynthetic optimization faces the challenges of high radiation
      exposure, cost, and inability to perform serial reactions due to tracer decay. To
      accelerate tracer development, we have developed a strategy to simulate
      radioactive 18 F-syntheses by using tracer-level (nanomolar) non-radioactive 19 F
      reagents and LC-MS/MS analysis. The methodology was validated with fallypride
      synthesis under tracer-level 19 F-conditions, which showed reproducible and
      comparable results with radiosynthesis, and proved the feasibility of this
      process. Using this approach, the synthesis of [18 F]MDL100907 was optimized
      under 19 F-conditions with greatly improved yield. The best conditions were
      successfully transferred to radiosynthesis. A radiochemical yield of 19% to 22%
      was achieved with the radiochemical purity >99% and the molar activity 38.8 to
      53.6 GBq/ MUmol (n = 3). The tracer-level 19 F-approach provides a high
      throughput and cost-effective process to optimize radiosynthesis with reduced
      radiation exposure. This new method allows medicinal and synthetic chemists to
      optimize radiolabeling conditions without the need to use radioactivity.

PMID- 29336066
TI  - Medication use and association with urinary incontinence in women: Data from the
      Norwegian Prescription Database and the HUNT study.
AB  - AIMS: To investigate the association between medication use and urinary
      incontinence (UI) in women. METHODS: In a cross-sectional population-based study
      we analyzed questionnaire data on UI, including type and severity, from 21 735
      women included in the Nord-Trondelag Health Study (HUNT) in Norway. These data
      were linked to data on filled prescriptions retrieved from the Norwegian
      Prescription Database. A multivariate logistic regression model was used to
      calculate the odds for having UI related to the number of filled prescriptions
      for selected drug groups during the 6 months prior to participation in HUNT,
      after adjustment for numerous confounding factors. RESULTS: Significant
      associations with UI were found for selective serotonin reuptake inhibitors
      (SSRIs) and lamotrigine with OR 1.52 (1.30-1.78) and 2.73 (1.59-4.68) for two or
      more filled prescriptions. Both for SSRIs and lamotrigine, the associations were
      pronounced for mixed UI, whereas there were no clear-cut increased risk of stress
      UI and urgency UI. The relations were strongest in women with the most severe
      symptoms. One filled prescription of antipsychotics, but not two or more, was
      also found to be related to UI with OR 1.91 (1.35-2.71). No associations were
      found for benzodiazepines, zopiclone/zolpidem, beta blockers, and diuretics.
      CONCLUSIONS: The odds for having UI were found to be about 1.5-fold in women
      using SSRIs and almost threefold in women using lamotrigine. The association with
      lamotrigine has not been reported previously, and should be further evaluated in
      future studies.

PMID- 29336068
TI  - Isatin, an endogenous nonpeptide biofactor: A review of its molecular targets,
      mechanisms of actions, and their biomedical implications.
AB  - Isatin (indole-2,3-dione) is an oxidized indole. It is widely distributed in
      mammalian tissues and body fluids, where isatin concentrations vary significantly
      from <0.1 to > 10 uM. Isatin output is increased under conditions of stress.
      Exogenously administered isatin is characterized by low toxicity, mutagenicity,
      and genotoxicity in vivo. Cytotoxic effects of isatin on various cell cultures
      are usually observed at concentrations exceeding 100 uM. Binding of [3 H]isatin
      to rat brain sections is consistent with its physiological concentrations.
      Proteomic analysis of mouse and rat brain isatin-binding proteins revealed about
      90 individual proteins, which demonstrated significant interspecies differences
      (rat versus mouse). Certain evidence exist that redox state(s) and possibly other
      types of posttranslational modifications regulate affinity of target proteins to
      isatin. Recent data suggest that interacting with numerous intracellular isatin
      binding proteins, isatin can act as a regulator of complex protein networks in
      norm and pathology. Physiological concentrations of isatin in vitro inhibit
      monoamine oxidase B and natriuretic peptide receptor guanylate cyclase, higher
      (neuroprotective) concentrations (50-400 MUM) cause apoptosis of various
      (including malignant tumor) cell lines and influence expression of certain
      apoptosis-related genes. Being administered in vivo, isatin exhibits various
      behavioral effects; it attenuates manifestations of MPTP-induced parkinsonism and
      tumor growth in experimental animal models. (c) 2017 BioFactors, 44(2):95-108,
      2018.

PMID- 29336069
TI  - An examination of the interaction between morality and self-control in offending:
      A study of differences between girls and boys.
AB  - BACKGROUND: There is a well-documented gender difference in offending, with
      evidence that boys, on average, are more involved in crime than girls. Opinions
      differ, however, on whether the causes of crime apply to girls and boys
      similarly. AIMS: Our aim is to explore crime propensity in boys and girls. Our
      research questions were (1) are there differences between boys and girls in moral
      values and self-control; (2) are these attributes similarly correlated with
      offending among girls and boys; and (3) is any interaction effect between
      morality and self-control identical for girls and boys. METHODS: Data were drawn
      from the Malmo Individual and Neighbourhood Development Study, which includes 481
      girls and boys aged 16-17. An 8-item self-control scale was derived from
      Grasmick's self-control instrument; we created a 16-item morality scale. Analysis
      of variance was used to test for differences in scale scores. RESULTS: There were
      significant gender differences in moral values but not self-control. Moral values
      and self-control were significantly correlated with offending among both girls
      and boys. In the multiple regression analysis, the three-way interaction term
      used to test the interaction between gender, self-control and moral values was
      non-significant, indicating that the magnitude of the self-control-moral value
      interaction is not affected by gender. CONCLUSIONS: Our findings indicate that
      effects of morality and self-control are general and apply to girls and boys
      similarly, so more research is needed to explain gender differences in crime
      prevalence. (c) 2018 The Authors Criminal Behaviour and Mental Health Published
      by John Wiley & Sons Ltd.

PMID- 29336070
TI  - Changes in surface characteristics of titanium and zirconia after surface
      treatment with ultraviolet light or non-thermal plasma.
AB  - Positive effects of irradiation with ultraviolet (UV) light or treatment with non
      thermal plasma on titanium and zirconia surfaces have been described in various
      studies. The aim of this study was to assess and compare the changes in the
      physicochemical surface conditions of titanium and zirconia surfaces after a
      short treatment with UV light or with non-thermal plasmas of argon or oxygen.
      Titanium and zirconia samples with moderately rough surfaces were treated for 12
      min either in a UV-light oven or in a non-thermal plasma reactor that generates
      non-thermal plasmas of oxygen or argon. Changes in surface conditions were
      assessed by confocal microscopy, dynamic contact angle measurement, and X-ray
      photoelectron spectroscopy (XPS). No changes in roughness occurred. Ultraviolet
      irradiation and non-thermal plasma significantly increased the wettability of the
      titanium and zirconia surfaces. X-ray photoelectron spectroscopy showed an
      increase of oxygen and a significant decrease of carbon after treatment with
      either method. Thus, ultraviolet light and non-thermal plasma were found to be
      able to improve the chemical surface conditions of titanium and zirconia
      following a short exposure time. However, further in vitro and in vivo studies
      are needed to determine the relevance of the results.

PMID- 29336071
TI  - Hierarchical N-Rich Carbon Sponge with Excellent Cycling Performance for Lithium
      Sulfur Battery at High Rates.
AB  - Lithium-sulfur batteries (LSBs) are receiving extensive attention because of
      their high theoretical energy density. However, practical applications of LSBs
      are still hindered by their rapid capacity decay and short cycle life, especially
      at high rates. Herein, a highly N-doped (~13.42 at %) hierarchical carbon sponge
      (HNCS) with strong chemical adsorption for lithium polysulfide is fabricated
      through a simple sol-gel route followed by carbonization. Upon using the HNCS as
      the sulfur host material in the cathode and an HNCS-coated separator, the battery
      delivers an excellent cycling stability with high specific capacities of 424 and
      326 mA h g-1 and low capacity fading rates of 0.033 % and 0.030 % per cycle after
      1000 cycles under high rates of 5 and 10 C, respectively, which are superior to
      those of other reported carbonaceous materials. These impressive cycling
      performances indicate that such a battery could promote the practical application
      prospects of LSBs.

PMID- 29336067
TI  - Treatment of allergic rhinitis using mobile technology with real-world data: The
      MASK observational pilot study.
AB  - BACKGROUND: Large observational implementation studies are needed to triangulate
      the findings from randomized control trials as they reflect "real-world" everyday
      practice. In a pilot study, we attempted to provide additional and complementary
      insights on the real-life treatment of allergic rhinitis (AR) using mobile
      technology. METHODS: A mobile phone app (Allergy Diary, freely available in
      Google Play and Apple App stores) collects the data of daily visual analog scales
      (VAS) for (i) overall allergic symptoms, (ii) nasal, ocular, and asthma symptoms,
      (iii) work, as well as (iv) medication use using a treatment scroll list
      including all medications (prescribed and over the counter (OTC)) for rhinitis
      customized for 15 countries. RESULTS: A total of 2871 users filled in 17 091 days
      of VAS in 2015 and 2016. Medications were reported for 9634 days. The assessment
      of days appeared to be more informative than the course of the treatment as, in
      real life, patients do not necessarily use treatment on a daily basis; rather,
      they appear to increase treatment use with the loss of symptom control. The
      Allergy Diary allowed differentiation between treatments within or between
      classes (intranasal corticosteroid use containing medications and oral H1
      antihistamines). The control of days differed between no [best control], single,
      or multiple treatments (worst control). CONCLUSIONS: This study confirms the
      usefulness of the Allergy Diary in accessing and assessing everyday use and
      practice in AR. This pilot observational study uses a very simple assessment
      (VAS) on a mobile phone, shows novel findings, and generates new hypotheses.

PMID- 29336072
TI  - Re: Re: Karabakan M, Bozkurt A, Hirik E, Celebi B, Akdemir S, Guzel O, Nuhoglu B.
      The prevalence of premature ejaculation in young Turkish men. Andrologia 2016;
      24: 1-5.

PMID- 29336073
TI  - Hypoxia-ischemia and brain injury in infants born preterm.

PMID- 29336074
TI  - Closing the knowledge gap in Mexico: towards evidence-based medicine in childhood
      disability.

PMID- 29336075
TI  - What causes the encephalopathy of prematurity?

PMID- 29336076
TI  - Cerebral palsy and genomics: an international consortium.

PMID- 29336077
TI  - Perspectives on caring for the child and the caregiver.

PMID- 29336078
TI  - The novel Axonics(r) rechargeable sacral neuromodulation system: Procedural and
      technical impressions from an initial North American experience.
AB  - AIMS: The rechargeable Axonics(r) r-SNMTM System is currently approved and
      available in Europe and Canada, with US FDA approval pending. This article
      provides a review of the system along with technique and technical considerations
      for its implantation based on my clinical experience with the new Axonics r-SNM
      System. METHODS: The description of the surgical technique and technological
      considerations for the Axonics r-SNM System is based my clinical experience of 11
      cases performed at UHN Toronto Western Hospital. RESULTS: While the Axonics
      system is intended to provide similar therapy to the existing SNM system, the
      Axonics system has several new technological advances. Understanding these
      differences and optimizing surgical technique is anticipated to improve outcomes
      and patient experience. CONCLUSIONS: Overall the Axonics r-SNM System and implant
      procedure requires minimal learning curve for experienced SNM implanters and
      provides several enhanced features for physicians and patients. Further
      experience by others may elucidate other nuances important to the implantation of
      this novel SNM system.

PMID- 29336079
TI  - The low FODMAP diet in the management of irritable bowel syndrome: an evidence
      based review of FODMAP restriction, reintroduction and personalisation in
      clinical practice.
AB  - Dietary restriction of fermentable oligosaccharides, disaccharides,
      monosaccharides and polyols (FODMAPs) is effective in the management of
      functional gastrointestinal symptoms that occur in irritable bowel syndrome
      (IBS). Numerous reviews have been published regarding the evidence for their
      restriction in the low FODMAP diet; however, few reviews discuss the
      implementation of the low FODMAP diet in practice. The aim of this review is to
      provide practical guidance on patient assessment and the implementation and
      monitoring of the low FODMAP diet. Broadly speaking, the low FODMAP diet consists
      of three stages: FODMAP restriction; FODMAP reintroduction; and FODMAP
      personalisation. These stages can be covered in at least two dietetic
      appointments. The first appointment focuses on confirmation of diagnosis,
      comprehensive symptom and dietary assessment, detailed description of FODMAPs and
      their association with symptom induction, followed by counselling regarding
      FODMAP restriction. Dietary counselling should be tailored to individual needs
      and appropriate resources provided. At the second appointment, symptoms and diet
      are re-assessed and, if restriction has successfully reduced IBS symptoms,
      education is provided on FODMAP reintroduction to identify foods triggering
      symptoms. Following this, the patient can follow FODMAP personalisation for which
      a less restrictive diet is consumed that excludes their personal FODMAP triggers
      and enables a more diverse dietary intake. This review provides evidence and
      practice guidance to assist in delivering high-quality clinical service in
      relation to the low FODMAP diet.

PMID- 29336080
TI  - Special issues for a special community.

PMID- 29336081
TI  - Measurement of long-range heteronuclear coupling constants using the peak
      intensity in classical 1D HMBC spectra.
AB  - In this contribution, we show that the magnitude of heteronuclear long-range
      coupling constants can be directly extracted from the classical 1D HMBC spectra,
      as all multiplet lines of a cross-peak always and exclusively vanish for the
      condition Delta = k/n JCH . To the best of our knowledge, this feature of the
      classical HMBC has not yet been noticed and exploited. This condition holds true,
      irrespective of the magnitude and numbers of additional active and passive
      homonuclear n JHH' couplings. Alternatively, the n JCH value may also be
      evaluated by fitting the peak's intensity in the individual spectra to its simple
      sin(pin JCH Delta)exp(-Delta/T2eff ) dependence. Compared to the previously
      proposed J-HMBC sequences that also use the variation of the cross-peak's
      intensity for extracting the coupling constants, the classical HMBC pulse
      sequence is significantly more sensitive.

PMID- 29336082
TI  - Metabolomics Study of Cultivated Bulbus Fritillariae Cirrhosae at Different
      Growth Stages using UHPLC-QTOF-MS Coupled with Multivariate Data Analysis.
AB  - INTRODUCTION: Bulbus fritillariae cirrhosae (known as Chuan bei mu in China, BFC)
      contain fritillaria steroidal alkaloids as the bioactive ingredients and are
      widely used as traditional Chinese medicine for the treatment of cough and
      phlegm. Due to limited wild resources, the cultivated species are becoming
      predominantly used in Chinese traditional medicine markets. OBJECTIVE: To assess
      the impact of different growth stages on the alkaloids of cultivated BFC and
      establish a reference for quality control and guidance for appropriate harvesting
      practices. METHODS: The ultra-high performance liquid chromatography quadrupole
      time-of-flight mass spectrometry (UHPLC-QTOF-MS) metabolomic strategy was applied
      to determine potential chemical markers for the discrimination and quality
      control of cultivated BFC in different growth stages. The molecular feature
      extraction and multivariate statistical analysis were applied to alkaloid
      extraction and full metabolomic profiling of cultivated BFC for classification
      and marker compound characterisation. RESULT: This approach allowed the
      establishment of a fast and efficient comparative multivariate analysis of the
      metabolite composition of 42 samples covering growth of cultivated BFC ranging in
      age from one to seven years old. Four alkaloid compounds were identified in
      cultivated BFC based on accurate mass, retention time, and MS/MS fragments. These
      compounds may be used as potential chemical markers for the classification and
      discrimination of cultivated BFC samples indifferent growth stages. CONCLUSIONS:
      The proposed analytical method in combination with multivariate statistical
      analysis comprised a useful and powerful strategy to explore the chemical
      ingredients and transforming mechanisms of cultivated BFC and for quality
      evaluation and control. Copyright (c) 2018 John Wiley & Sons, Ltd.

PMID- 29336083
TI  - How sea level change mediates genetic divergence in coastal species across
      regions with varying tectonic and sediment processes.
AB  - Plate tectonics and sediment processes control regional continental shelf
      topography. We examine the genetic consequences of how glacial-associated sea
      level change interacted with variable nearshore topography since the last
      glaciation. We reconstructed the size and distribution of areas suitable for
      tidal estuary formation from the last glacial maximum, ~20 thousand years ago, to
      present from San Francisco, California, USA (~38 degrees N) to Reforma, Sinaloa,
      Mexico (~25 degrees N). We assessed range-wide genetic structure and diversity of
      three codistributed tidal estuarine fishes (California Killifish, Shadow Goby,
      Longjaw Mudsucker) along ~4,600 km using mitochondrial control region and cytB
      sequence, and 16-20 microsatellite loci from a total of 524 individuals. Results
      show that glacial-associated sea level change limited estuarine habitat to few,
      widely separated refugia at glacial lowstand, and present-day genetic clades were
      sourced from specific refugia. Habitat increased during postglacial sea level
      rise and refugial populations admixed in newly formed habitats. Continental
      shelves with active tectonics and/or low sediment supply were steep and hosted
      fewer, smaller refugia with more genetically differentiated populations than on
      broader shelves. Approximate Bayesian computation favoured the refuge
      recolonization scenarios from habitat models over isolation by distance and
      seaway alternatives, indicating isolation at lowstand is a major diversification
      mechanism among these estuarine (and perhaps other) coastal species. Because sea
      level change is a global phenomenon, we suggest this top-down physical control of
      extirpation-isolation-recolonization may be an important driver of genetic
      diversification in coastal taxa inhabiting other topographically complex coasts
      globally during the Mid- to Late Pleistocene and deeper timescales.

PMID- 29336084
TI  - Age onset of offending and serious mental illness among forensic psychiatric
      patients: A latent profile analysis.
AB  - BACKGROUND: Developmental typologies regarding age of onset of violence and
      offending have not routinely taken account of the role of serious mental illness
      (SMI), and whether age of onset of offending in relation to onset of illness
      impacts on the manifestation of offending over the life course. AIMS: To test
      whether forensic psychiatric patients can be classified according to age of onset
      of SMI and offending, and, if so, whether subtypes differ by sex. METHODS:
      Details of all 511 patients enrolled into a large forensic mental health service
      in Ontario, Canada, in 2011 or 2012 were collected from records. RESULTS: A
      latent profile analysis supported a 2-class solution in both men and women.
      External validation of the classes demonstrated that those with a younger age
      onset of serious mental illness and offending were characterised by higher levels
      of static risk factors and criminogenic need than those whose involvement in both
      mental health and criminal justice systems was delayed to later life.
      CONCLUSIONS: Our findings present a new perspective on life course trajectories
      of offenders with SMI. While analyses identified just two distinct age-of-onset
      groups, in both the illness preceded the offending. The fact that our sample was
      entirely drawn from those hospitalised may have introduced a selection bias for
      those whose illness precedes offending, but findings underscore the complexity
      and level of need among those with a younger age of onset. Copyright (c) 2018
      John Wiley & Sons, Ltd.

PMID- 29336085
TI  - Endotracheal tube placement during computed tomography of brachycephalic dogs
      alters upper airway dimensional measurements.
AB  - Computed tomography (CT) is used to document upper airway lesions in dogs with
      brachycephalic obstructive airway syndrome. The presence of an endotracheal tube
      during CT scanning is often required for general anesthesia. We hypothesized that
      the endotracheal tube placement would change the soft tissue dimensions of the
      upper airway. The aims of this prospective, method comparison study were to
      evaluate the reliability of the previously reported upper airway CT measurements
      with endotracheal tube placement, and to propose measurements that are minimally
      affected by the endotracheal tube. Twenty brachycephalic dogs were included in
      this study. Each dog underwent head/neck CT with an endotracheal tube, followed
      by a second scan without the endotracheal tube. Ten measurements of the soft
      palate, nasopharynx, and trachea were performed. Tracheal dimension was
      significantly larger with the endotracheal tube compared to without, whereas the
      soft palate cross-sectional area was significantly smaller with the endotracheal
      tube than without the endotracheal tube. The influence of the endotracheal tube
      on the caudal nasopharynx cross-sectional (transverse-sectional) area varied with
      a mean proportional absolute difference of 35%. Rostral soft palate thickness,
      tracheal perimeter, and cross-sectional area of the rostral nasopharynx were the
      measurements least affected by the endotracheal tube (intraclass correlation
      coefficient = 0.964, 0.967, and 0.951, respectively). Therefore, we proposed that
      these three measurements may be most useful for future brachycephalic obstructive
      airway syndrome studies that require CT scanning of intubated animals. However,
      with endotracheal tube placement, measurements of soft palate length, caudal
      nasopharyngeal cross-sectional area, and trachea height and width may not be
      reliable.

PMID- 29336086
TI  - Learning to blast a way into crime, or just good clean fun? Examining aggressive
      play with toy weapons and its relation with crime.
AB  - BACKGROUND: Researchers, such as Bandura, have proposed that children's mere
      exposure to the use of play weapons encourages deviant displays of aggression,
      but there is very little research to support this hypothesis of 20 years. AIM: To
      examine the relationship between amount of weapon play and concurrent aggression
      as well as later violent juvenile crime, while controlling for other variables
      possibly influencing criminal pathways. METHOD: Using longitudinal survey data
      collected from mothers and children (n = 2019) from age 5, with follow-up at age
      15, correlations between children's play with toy weapons and juvenile
      criminality were examined. Multivariate regression analyses were employed to
      determine to what extent early childhood aggression, symptoms of attention
      deficit hyperactivity disorder, and symptoms of depression were antecedents of
      juvenile crime. RESULTS: For bivariate analysis between toy weapon play and
      juvenile criminality, the effect size was small and not significant. The
      relationship remained not significant once control variables were introduced into
      the model. CONCLUSIONS AND IMPLICATIONS: The act of pretending to be aggressive
      in childhood thus plays little role in predicting later criminality after other
      factors, such as gender, attention deficit hyperactivity disorder or depression,
      have been taken into account. Involvement in imaginative play with toy gun use in
      early childhood is unlikely to be useful as a risk marker for later criminal
      behaviour. Play fighting and war toy games may even be considered necessary
      components within the frame of normal development. Copyright (c) 2018 John Wiley
      & Sons, Ltd.

PMID- 29336087
TI  - New Stretching Method for Aligning Gels: Its Application to the Measurement
      Residual Chemical Shift Anisotropies (RCSAs) without the Need for Isotropic Shift
      Correction.
AB  - An existing gel stretching device is modified, permitting the use of organic
      solvents for the study of small molecules. Different from the original device,
      gels are stretched into 4 mm open-ended NMR tubes and then inserted into regular
      5 mm NMR tubes. No open-ended tubes are inserted in the NMR probe avoiding the
      risk of sample leaking. It is also shown that residual chemical shift
      anisotropies (RCSAs) measured with the device are free of isotropic shift
      interferences and corrections for them are not needed during the post-acquisition
      data analysis. Three internal references for chemical shift were evaluated (CCl4
      , CBr4 and TMS), being CCl4 the most convenient one to measure RCSAs in CDCl3 .
      RCSAs measured with the modified stretching device using CCl4 as the internal
      chemical shift reference were enough to determine the relative configuration of
      three small molecules with an excellent degree of configuration discrimination.

PMID- 29336088
TI  - Casual movement speed but not maximal locomotor capacity predicts mate searching
      success.
AB  - Maximal locomotor performance is often used as a proxy for fitness. Maximal speed
      may be important under high-threat conditions, such as during predator escape.
      However, animals do not always move at a speed that reflects their maximal
      physiological capacities when undisturbed. The physiological factors that
      determine the movement speed chosen by animals, such as minimization of energy
      use, may be independent from maximal performance. As a result, the casual speed
      at which individuals move when undisturbed in a given context may better
      represent an individual's motivation to move. The casual speed may therefore be a
      better predictor of fitness in natural contexts than maximal performance
      capacity. We tested the hypothesis that casual movement speed rather than maximal
      speed predicts fitness in the golden orb-web spider, Nephila plumipes. We
      measured fitness in two separate contexts, mate-searching success and the
      positional rank near a female. We show that casual but not maximal locomotor
      speed predicted both aspects of fitness. Casual speed was linearly related to
      maximal speed, indicating that casual speed is determined by physiological
      optimization. Size and metabolic scope were not related to either maximal or
      chosen speeds, indicating that the supply of ATP does not limit locomotor
      performance in this species. Overall, our results demonstrate that locomotor
      performance is related to fitness, but suggest that different types of
      performance and not necessarily maximal physiological capacities are most
      relevant for particular ecologically relevant tasks.

PMID- 29336089
TI  - Corrigendum.

PMID- 29336090
TI  - Microsphere Assemblies via Phosphonate Monoester Coordination Chemistry.
AB  - By complexing a bent phosphonate monoester ligand with cobalt(II), coupled with
      in situ ester hydrolysis, coordination microspheres (CALS=CALgary Sphere) are
      formed whereas the use of the phosphonic acid directly resulted in a sheet-like
      structure. Manipulation of the synthetic conditions gave spheres with different
      sizes, mechanical stabilities, and porosities. Time-dependent studies determined
      that the sphere formation likely occurred through the formation of a Co2+ and
      ligand chain that propagates in three dimensions through different sets of
      interactions. The relative rates of these assembly processes versus annealing by
      ester hydrolysis and metal dehydration determine the growth of the microspheres.
      Hardness testing by nanoindentation is carried out on the spheres and sheets.
      Notably, no templates or capping agents are employed, the growth of the spheres
      is intrinsic to the ligand geometry and the coordination chemistry of cobalt(II)
      and the phosphonate monoester.

PMID- 29336092
TI  - Development and validation of a scoring system to predict progression to acute-on
      chronic liver failure in patients with acute exacerbation of chronic hepatitis B.
AB  - AIM: The aim of this study was to develop and validate a scoring system to
      predict the progression to acute-on-chronic liver failure (ACLF) in patients with
      acute exacerbation (AE) of chronic hepatitis B (CHB). METHODS: The baseline
      characteristics of 474 patients with AE of CHB were retrospectively reviewed; 280
      and 194 patients were randomly assigned to the derivation and validation cohorts,
      respectively. Univariate risk factors associated with ACLF development were
      entered into a multivariate logistic regression. The score model was established,
      and its predictive value was evaluated by the receiver operating characteristic
      (ROC) curve and the area under the ROC curve (AUROC). RESULTS: Hepatitis B virus
      (HBV) DNA, international normalized ratio (INR) of prothrombin time, and patient
      age were identified as independent risk factors associated with progressing to
      ACLF. The prediction model was established as R = -13.323 + 0.553 * log HBV-DNA
      (copies/mL) + 3.631* INR + 0.053 * age. The AUROCs of our prediction model were
      higher than those of the Model for End-stage Liver Disease (MELD) and MELD-sodium
      (Na) for both cohorts. At the cut-off value of -2.43, our prediction model had
      higher sensitivity (87.5%), specificity (73.6%), positive predictive value
      (23.0%), positive likelihood ratio (3.30), and lower negative likelihood ratio
      (0.17) in the validation cohort than those of MELD and MELD-Na. CONCLUSION: The
      independent risk factors associated with progressing to ACLF in patients with AE
      of CHB are HBV-DNA, INR, and age. Our risk prediction model is useful for
      predicting the development of ACLF.

PMID- 29336093
TI  - Heart failure with mid-range ejection fraction: causes and consequences.

PMID- 29336091
TI  - Drug resistance in anaplastic lymphoma kinase-rearranged lung cancer.
AB  - The anaplastic lymphoma kinase (ALK) gene encodes a receptor tyrosine kinase, and
      many kinds of ALK fusion genes have been found in a variety of carcinomas. There
      is almost no detectable expression of ALK in adults. However, through ALK gene
      rearrangement, the resultant ALK fusion protein is aberrantly overexpressed and
      dimerized through the oligomerization domains, such as the coiled-coil domain, in
      the fusion partner that induces abnormal constitutive activation of ALK tyrosine
      kinase. This results in dysregulated cell proliferation. ALK gene rearrangement
      has been observed in 3%-5% of non-small-cell lung cancers, and multiple ALK
      inhibitors have been developed for the treatment of ALK-positive lung cancer.
      Among those inhibitors, in Japan, 3 (4 in the USA) ALK tyrosine kinase inhibitors
      (TKIs) have been approved and are currently used in clinics. All of the currently
      approved ALK-TKIs have been shown to induce marked tumor regression in ALK
      rearranged non-small-cell lung cancer; however, tumors inevitably relapse because
      of acquired resistance within a few years. This review focuses on ALK-TKIs, their
      resistance mechanisms, and the potential therapeutic strategies to overcome
      resistance.

PMID- 29336095
TI  - Sleep hygiene, insomnia and mental health.

PMID- 29336094
TI  - Sympathetic neurovascular regulation during pregnancy: A longitudinal case series
      study.
AB  - NEW FINDINGS: What is the main observation in this case? The main observation of
      this case report is that during pregnancy there is a progressive sympatho
      excitation in basal conditions and under stress, which is offset by a concurrent
      reduction in neurovascular transduction. Strong correlations between autonomic
      nervous system activity and sex hormones (oestrogen and progesterone),
      vasopressin and aldosterone were found. What insights does it reveal? Our
      findings suggest that hormonal surges might be associated with central
      sympathetic activation. ABSTRACT: The adaptations of sympathetic nerve activity
      (SNA) during pregnancy remain poorly understood. An increase in blood volume,
      cardiac output and SNA, with a concomitant drop in total peripheral resistance
      (TPR), suggest that during pregnancy there is a reduced transduction of SNA into
      TPR. Most of these findings have originated from cross-sectional studies; thus,
      we conducted a longitudinal assessment of SNA and TPR in two participants.
      Measurements were made before pregnancy (early follicular phase), on four
      occasions during pregnancy and at 2 months postpartum. Mean arterial pressure and
      cardiac output were used to calculate TPR. The SNA was measured using
      microneurography (peroneal nerve). There was a gestation-dependent increase in
      SNA burst frequency (r2  = 0.96, P = 0.009). Neurovascular transduction, however,
      decreased by 53% in both women. Sympathetic hyperactivity was reversed
      postpartum, whereas neurovascular transduction remained lower. These longitudinal
      data highlight the progressive sympatho-excitation of pregnancy, which is offset
      by a concurrent reduction in neurovascular transduction.

PMID- 29336096
TI  - Fe2 Si5 N8 : Access to Open-Shell Transition-Metal Nitridosilicates.
AB  - Highly condensed nitridosilicates doped with Eu2+ or Ce3+ play an important role
      in saving energy by converting the blue light of (In,Ga)N-LEDs. Although
      nitridosilicates are known for great structural variety based on covalent anionic
      Si-N networks, elemental variety is restricted. Presenting a significant
      extension of the latter, this work describes a general access to open-shell
      transition-metal nitridosilicates. As a proof-of-principle, the first iron
      nitridosilicate, namely Fe2 Si5 N8 , was prepared by exchanging Ca2+ in alpha-Ca2
      Si5 N8 applying a FeCl2 melt (salt metathesis). The title compound was analyzed
      by powder X-ray diffraction, EDX, ICP-OES, combustion analysis, TG/DSC, Mossbauer
      spectroscopy and magnetic susceptibility measurements. Furthermore, the structure
      of alpha-Ca2 Si5 N8 was determined at 1073 and 1173 K confirming the anionic
      network of alpha-Ca2 Si5 N8 providing possible migration pathways for the ion
      exchange reaction.

PMID- 29336097
TI  - Identification of dementia using standard clinical assessments by primary care
      physicians in Japan.
AB  - AIM: The aim of the present study was to develop a way of identifying dementia
      using clinical assessments made by primary care physicians under the existing
      medical care system in Japan. METHODS: A total of 623 people aged >=65 years
      underwent standard clinical assessments by primary care physicians under the long
      term-care insurance program to determine their grade of activities of daily
      living related to dementia. To examine the validity of the diagnosis,
      neuropsychiatrists carried out further diagnosis of dementia for all the
      participants. We regarded the dementia patients who received care for disability
      under the long-term care insurance program as having disabling dementia. RESULTS:
      Multivariable odds ratio (95% confidence interval) in single-grade increments of
      the activity was 2.1 (1.7-2.5) for dementia and 2.8 (2.2-3.4) for disabling
      dementia. The grades >=I and >=IIa were near the upper-left corner in the
      receiver operating characteristic curves. Setting the cut-off point at grades >=I
      or >=IIa yielded a higher integrated discrimination improvement, suggesting a
      major improvement in reducing misclassification by using these cut-off points.
      When we used grades >=I as the cut-off point, the sensitivity (95% confidence
      limits) was 65% (58-72%) and the specificity was 93% (91-96%) for dementia, and
      the corresponding values in grades >=IIa were 54% (47-62%) and 96% (94-97%). The
      corresponding values for disabling dementia were 83% (76-90%), 92% (90-95%), 73%
      (65-80%) and 96% (94-97%). CONCLUSIONS: Our findings suggest that selection of
      grades >=I or >=IIa as the cut-off point would reduce instances of
      misclassification in the identification of dementia and disabling dementia.
      Geriatr Gerontol Int 2018; 18: 738-744.

PMID- 29336098
TI  - Increasing the knowledge, identification and treatment of osteoporosis through
      education and shared decision-making with residents living in a retirement
      village community.
AB  - OBJECTIVE: This pilot study explored whether individual goal setting in a
      retirement village setting could improve strategies to strengthen bones in an
      ageing population and help prevent osteoporosis. METHODS: A two-phased
      osteoporosis prevention program was developed, piloted and evaluated involving a
      group education session followed by the development of individualised Bone Plans
      based upon personal understanding of individual fracture risk and lifestyle
      factors. RESULTS: A significant improvement in knowledge and understanding of
      factors to prevent and manage osteoporosis was achieved, and changes in lifestyle
      behaviours were sustained at six months. CONCLUSION: Success was due to education
      by specialist medical and health personnel, flexibility of goal setting, use of
      group sessions and location of the program within the retirement community
      setting. The 'Mind Your Bones' program is a feasible and acceptable way to
      translate preventative bone health messages to a large number of people via the
      retirement village network.

PMID- 29336099
TI  - Evolving rationale for post-mastectomy radiation.

PMID- 29336100
TI  - Silver(I)-Catalyzed Widely Applicable Aerobic 1,2-Diol Oxidative Cleavage.
AB  - The oxidative cleavage of 1,2-diols is a fundamental organic transformation. The
      stoichiometric oxidants that are still predominantly used for such oxidative
      cleavage, such as H5 IO6  , Pb(OAc)4  , and KMnO4  , generate stoichiometric
      hazardous waste. Herein, we describe a widely applicable and highly selective
      silver(I)-catalyzed oxidative cleavage of 1,2-diols that consumes atmospheric
      oxygen as the sole oxidant, thus serving as a potentially greener alternative to
      the classical transformations.

PMID- 29336101
TI  - Recurrence of vulval intraepithelial neoplasia following treatment with cidofovir
      or imiquimod: results from a multicentre, randomised, phase II trial (RT3VIN).
AB  - OBJECTIVE: To compare the recurrence rates after complete response to topical
      treatment with either cidofovir or imiquimod for vulval intraepithelial neoplasia
      (VIN) 3. DESIGN: A prospective, open, randomised multicentre trial. SETTING: 32
      general hospitals located in Wales and England. POPULATION OR SAMPLE: 180
      patients were randomised consecutively between 21 October 2009 and 11 January
      2013, 89 to cidofoovir (of whom 41 completely responded to treatment) and 91 to
      imiquimod (of whom 42 completely responded to treatment). METHODS: After 24 weeks
      of treatment, complete responders were followed up at 6-monthly intervals for 24
      months. At each visit, the Common Terminology Criteria for Adverse Events (CTCAE)
      v3.0 was assessed and any new lesions were biopsied for histology. MAIN OUTCOME
      MEASURES: Time to histologically confirmed disease recurrence (any grade of VIN).
      RESULTS: The median length of follow up was 18.4 months. At 18 months, more
      participants were VIN-free in the cidofovir arm: 94% (95% CI 78.2-98.5) versus
      71.6% (95% CI 52.0-84.3) [univariable hazard ratio (HR) 3.46, 95% CI 0.95-12.60,
      P = 0.059; multivariable HR 3.53, 95% CI 0.96-12.98, P = 0.057). The number of
      grade 2+ events was similar between treatment arms (imiquimod: 24/42 (57%) versus
      cidofovir: 27/41 (66%), chi2 = 0.665, P = 0.415), with no grade 4+. CONCLUSIONS:
      Long-term data indicates a trend towards response being maintained for longer
      following treatment with cidofovir than with imiquimod, with similar low rates of
      adverse events for each drug. Adverse event rates indicated acceptable safety of
      both drugs TWEETABLE ABSTRACT: Long-term follow up in the RT3VIN trial suggests
      cidofovir may maintain response for longer than imiquimod.

PMID- 29336102
TI  - Behavioural responses of the yellow emitting annelid Tomopteris helgolandica to
      photic stimuli.
AB  - In contrast to most mesopelagic bioluminescent organisms specialised in the
      emission and reception of blue light, the planktonic annelid Tomopteris
      helgolandica produces yellow light. This unusual feature has long been suggested
      to serve for intraspecific communication. Yet, this virtually admitted hypothesis
      has never been tested. In this behavioural study of spectral colour sensitivity,
      we first present an illustrated repertoire of the postures and action patterns
      described by captive specimens. Then video tracking and motion analysis are used
      to quantify the behavioural responses of singled out worms to photic stimuli
      imitating intraspecific (yellow) or interspecific (blue) bioluminescent signals.
      We show the ability of T. helgolandica to react and to contrast its responses to
      bioluminescent-like blue and yellow light signals. In particular, the attractive
      effect of yellow light and the variation of angular velocity observed according
      to the pattern of yellow stimuli (flashes versus glows) support the intraspecific
      communication hypothesis. However, given the behavioural patterns of T.
      helgolandica, including mechanically induced light emission, the possibility that
      bioluminescence may be part of escape/defence responses to predation, should
      remain an open question.

PMID- 29336103
TI  - Staff preparedness for providing palliative and end-of-life care in long-term
      care homes: Instrument development and validation.
AB  - AIM: Although much attention has been on integrating the palliative care approach
      into services of long-term care homes for older people living with frailty and
      progressive diseases, little is known about the staff preparedness for these new
      initiatives. The present study aimed to develop and test the psychometric
      properties of an instrument for measuring care home staff preparedness in
      providing palliative and end-of-life care. METHODS: A 16-item instrument,
      covering perceived knowledge, skill and psychological readiness, was developed. A
      total of 247 staff members of different ranks from four care homes participated
      in the study. Exploratory factor analysis using the principal component analysis
      extraction method with varimax rotation was carried out for initial validation.
      Known group comparison was carried out to examine its discriminant validity.
      Reliability of the instrument was assessed based on test-retest reliability of a
      subsample of 20 participants and the Cronbach's alpha of the items. RESULTS:
      Exploratory factor analysis showed that the instrument yielded a three-factor
      solution, which cumulatively accounted for 68.5% of the total variance. Three
      subscales, namely, willingness, capability and resilience, showed high internal
      consistency and test-retest reliability. It also showed good discriminant
      validity between staff members of professional and non-professional groups.
      CONCLUSIONS: This is a brief, valid and reliable scale for measuring care home
      staff preparedness for providing palliative and end-of-life care. It can be used
      to identify their concerns and training needs in providing palliative and end-of
      life care, and as an outcome measure to evaluate the effects of interventional
      studies for capacity building in this regard. Geriatr Gerontol Int 2018; 18: 745
      749.

PMID- 29336104
TI  - Early intervention in bipolar disorders: Where we are now and need to go next.

PMID- 29336105
TI  - Senescence chips for ultrahigh-throughput isolation and removal of senescent
      cells.
AB  - Cellular senescence plays an important role in organismal aging and age-related
      diseases. However, it is challenging to isolate low numbers of senescent cells
      from small volumes of biofluids for downstream analysis. Furthermore, there is no
      technology that could selectively remove senescent cells in a high-throughput
      manner. In this work, we developed a novel microfluidic chip platform, termed
      senescence chip, for ultrahigh-throughput isolation and removal of senescent
      cells. The core component of our senescence chip is a slanted and tunable 3D
      micropillar array with a variety of shutters in the vertical direction for rapid
      cell sieving, taking advantage of the characteristic cell size increase during
      cellular senescence. The 3D configuration achieves high throughput, high recovery
      rate, and device robustness with minimum clogging. We demonstrated proof-of
      principle applications in isolation and enumeration of senescent mesenchymal stem
      cells (MSCs) from undiluted human whole blood, and senescent cells from mouse
      bone marrow after total body irradiation, with the single-cell resolution. After
      scale-up to a multilayer and multichannel structure, our senescence chip achieved
      ultrahigh-throughput removal of senescent cells from human whole blood with an
      efficiency of over 70% at a flow rate of 300 ml/hr. Sensitivity and specificity
      of our senescence chips could be augmented with implementation of multiscale size
      separation, and identification of background white blood cells using their cell
      surface markers such as CD45. With the advantages of high throughput, robustness,
      and simplicity, our senescence chips may find wide applications and contribute to
      diagnosis and therapeutic targeting of cellular senescence.

PMID- 29336106
TI  - Best practice perioperative strategies and surgical techniques for preventing
      caesarean section surgical site infections: a systematic review of reviews and
      meta-analyses.
AB  - BACKGROUND: Surgical site infection (SSI) following caesarean section is a
      problem for women and health services. Caesarean section is a high volume
      procedure and the estimated incidence of SSI may be as high as 9%. OBJECTIVES:
      The objective of this study was to identify a suite of perioperative strategies
      and surgical techniques that reduce the risk of SSI following caesarean section.
      SEARCH STRATEGY: Six electronic databases were searched to systematically review
      literature reviews, systematic reviews and meta-analyses published from 2006 to
      2016. Search terms included: endometritis, SSI, caesarean section, meta-analysis,
      review, systematic. SELECTION CRITERIA: Studies were sought in which competing
      perioperative strategies and surgical techniques relevant for caesarean section
      were identified and quantifiable infection outcomes were reported. General
      infection control strategies were excluded. DATA COLLECTION AND ANALYSIS: Data on
      study characteristics and clinical effectiveness were extracted. Quality,
      including bias within individual studies, was examined using a modified A
      Measurement Tool to Assess Systematic Reviews (AMSTAR) checklist. Recommendations
      for SSI risk-reducing strategies were developed using the Grading of
      Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN
      RESULTS: Of 466 records retrieved, 44 studies were selected for the evidence
      synthesis. Recommended strategies were: administer pre-incision antibiotic
      prophylaxis, prepare the vagina with iodine-povidone solution and spontaneous
      placenta removal. CONCLUSIONS: We recommend clinicians implement pre-incision
      antibiotic prophylaxis, vaginal preparation and spontaneous placenta removal as
      an infection control bundle for caesarean section. FUNDING: Queensland University
      of Technology. TWEETABLE ABSTRACT: Infection control for caesarean: pre-incision
      AB prophylaxis, vaginal prep, spontaneous placenta removal.

PMID- 29336107
TI  - Centrality of spirituality/religion in the culture of palliative care service in
      Indonesia: An ethnographic study.
AB  - Experiencing life-threatening illness could impact on an individual's
      spirituality or religious beliefs. In this paper, we report on a study which
      explored cultural elements that influence the provision of palliative care for
      people with cancer. A contemporary ethnographic approach was adopted.
      Observations and interviews were undertaken over 3 months with 48 participants,
      including palliative care staff, patients, and their families. An ethnographic
      data analysis framework was adopted to assist in the analysis of data at item,
      pattern, and structural levels. Religion was identified as central to everyday
      life, with all participants reporting being affiliated to particular religions
      and performing their religious practices in their daily lives. Patients'
      relatives acknowledged and addressed patients' needs for these practices. Staff
      provided spiritual care for the patients and their relatives in the form of
      religious discussion and conducting prayers together. An understanding that
      religious and spiritual practices are integral cultural elements and of
      fundamental importance to the holistic health of their patients is necessary if
      health-care professionals are to support patients and their families in end-of
      life care.

PMID- 29336108
TI  - Reversible CO2 Addition to a Si=O Bond and Synthesis of a Persistent SiO2 -CO2
      Cycloadduct Stabilized by a Lewis Donor-Acceptor Ligand.
AB  - The donor-stabilized sila-beta-lactone 1 reacts with CO2 via a remarkable
      reversible [2+2]-cycloaddition reaction to form the spiro-cyclic silicon
      carbonate derivative 2. Furthermore, photolysis of 2 under pressure of CO2
      affords the first persistent SiO2 -CO2 cycloadduct 3, presenting a Si2 O4 -like
      structure, which is stabilized by a Lewis donor-acceptor type ligand. As
      predicted by theoretical calculations, in marked contrast to the
      thermodynamically stable SiO2 dimer, the SiO2 -CO2 mixed cycloadduct 3 is labile
      and readily releases CO2 .

PMID- 29336109
TI  - Moderate hypofractionation for prostate cancer: A user's guide.
AB  - Three large randomised controlled trials have been published in the last year
      demonstrating the non-inferiority of moderate hypofractionation compared to
      conventional fractionation for localised prostate cancer with respect to both
      disease control and late toxicity at 5 years. Furthermore, no clinically
      significant differences in patient-reported outcomes have emerged. More mature
      follow-up data are now also available from phase 2 studies confirming that
      moderate hypofractionation is associated with low rates of significant toxicity
      at 10 years. Moving forward it is likely that appropriate patient selection,
      integration of androgen deprivation and attention to optimising technique will
      play a more important role than modest differences in dose-fractionation
      schedules. Here we briefly review the evidence, discuss issues of patient
      selection and provide an approach to implementing moderately hypofractionated
      radiation therapy for prostate cancer in clinical practice.

PMID- 29336110
TI  - Stabilization of the Pentazolate Anion in a Zeolitic Architecture with Na20 N60
      and Na24 N60 Nanocages.
AB  - The experimental detection and synthesis of pentazole (HN5 ) and its anion (cyclo
      N5- ) have been actively pursued for the past hundred years. The synthesis of an
      aesthetic three-dimensional metal-pentazolate framework (denoted as MPF-1) is
      presented. It consists of sodium ions and cyclo-N5- anions in which the isolated
      cyclo-N5- anions are preternaturally stabilized in this inorganic open framework
      featuring two types of nanocages (Na20 N60 and Na24 N60 ) through strong metal
      coordination bonds. The compound MPF-1 is indefinitely stable at room temperature
      and exhibits high thermal stability relative to the reported cyclo-N5- salts.
      This finding offers a new approach to create metal-pentazolate frameworks (MPFs)
      and enables the future exploration of interesting pentazole chemistry and also
      related functional materials.

PMID- 29336111
TI  - Beyond mere pill taking: SMS reminders for HIV treatment adherence delivered to
      mobile phones of clients in a community support network in Australia.
AB  - SMS reminders sent to personal mobiles are increasingly used by clinical services
      to promote patient engagement, including adherence to antiretroviral treatment
      (ART) for HIV. From August to September 2015, a 6-week, randomised SMS reminder
      for ART adherence intervention was implemented among 98 HIV-positive clients of
      Australian's largest HIV charitable organisation located in Sydney. This was
      followed by a mixed-method evaluation, comprising a self-completed online survey
      and a one-to-one interview. Of the 62 survey participants, all being men, the
      majority were gay (85.5%) and living long-term with HIV (median year of HIV
      diagnosis = 1998). While everyone was on ART, a substantial proportion (n = 27,
      43.5%) had interrupted treatment in the past. At the end of the intervention,
      based on the standard SMAQ measure, 82% had consistently adhered to ART in the
      previous week. While there was no statistically significant intervention effect,
      perceiving less stigma were independently associated with better ART adherence
      (adjusted odds ratio = 0.37; 95% CI 0.16-0.89; P = .026). Of the 11 interviewees,
      despite limited add-on effects on individual ART adherence, the campaign was well
      received as a unique community support service. This study underscores the
      essential role of empowerment through enhancing disease self-management,
      increasing social support and reducing stigma, particularly for long-term HIV
      survivors. SMS messaging, part of mHealth, delivered by community services could
      have broader impacts on reducing health and social inequity.

PMID- 29336112
TI  - Is there an association of ABO blood groups and Rhesus factor with alopecia
      areata?
AB  - BACKGROUND/OBJECTIVES: Alopecia areata (AA) is an autoimmune disease
      characterized by noncicatricial hair loss localized on hair, beard, mustache,
      eyebrow, eyelash, and sometimes on the body. Although etiopathogenesis is not
      fully understood, many studies show remarkable associations between various
      diseases and ABO blood groups. However, there is no study with AA and blood
      groups. METHODS: Healthy people and patients with AA were included in this study.
      A total of 155 patients with AA and 299 healthy controls were included in the
      study. RESULTS: ABO blood group distribution in patients with AA and distribution
      of healthy donors were similar. However, Rhesus factor positivity in the AA group
      was significantly higher than in healthy donors. The relationship between stress
      and AA was high as known. But, ABO blood group and Rhesus factor were not in a
      significant connection with stress. CONCLUSION: We conclude that there was no
      association between ABO blood group and AA, but the observed distribution of
      Rhesus blood group differed slightly but significantly from that of the healthy
      population. The result of the study shows a small but statistically significant
      difference in the Rh blood group between patients with AA and the healthy
      population blood groups. This result is important because it suggests that
      genetic factors may influence the development of AA. The role of blood groups in
      the development of AA remains to be determined. We believe that the studies which
      will be carried out in other centers with wider series will be more valuable to
      support this hypothesis.

PMID- 29336113
TI  - Comments on Famulski and Halloran AJT i-IFTA letter.

PMID- 29336114
TI  - Nucleolar and spindle-associated protein 1 is a tumor grade correlated prognosis
      marker for glioma patients.
AB  - AIMS: Despite therapeutic advances in glioma management including surgery,
      radiation, and chemotherapy, the improvement of patient outcome is far from
      satisfactory. Nucleolar and spindle-associated protein 1 (NUSAP1) is an important
      functional protein during mitosis, and its abnormal expression is implicated in
      progression of different types of tumors. However, the role of NUSAP1 in gliomas
      remains unclear. METHODS: NUSAP1 expression in gliomas with different grades was
      investigated based on GEO glioma datasets. Kaplan-Meier survival analysis was
      used to evaluate its prognostic significance. In vitro assays were also performed
      to evaluate effects of NUSAP1 on malignant phenotypes of glioma cells by
      silencing NUSAP1. RESULTS: NUSAP1 expression was correlated not only with glioma
      grade but also with prognosis of glioma patients. NUSAP1 depletion suppressed
      proliferation of U251 cells by inducing cell cycle arrest at G2/M phase and
      apoptosis. NUSAP1 depletion rendered U251 cells impaired migratory ability as
      well. CONCLUSION: NUSAP1 is a potential prognosis marker for glioma patients and
      therapeutic strategies targeting NUSAP1 might hold promise in improving glioma
      treatment.

PMID- 29336115
TI  - Insight into the inhibitor discrimination by FLT3 F691L.
AB  - Fms-like tyrosine kinase 3 (FLT3) belongs to the receptor tyrosine kinase family
      and expressed in hematopoietic progenitor cells. FLT3 gene mutations are reported
      in ~30% of acute myeloid leukemia cases. FLT3 kinase domain mutation F691L is one
      of the common causes of acquired resistance to the FLT3 inhibitors including
      quizartinib. MZH29 and crenolanib were previously reported to inhibit FLT3 F691L.
      However, crenolanib was reported for the moderate inhibition. We found that
      Glu661and Asp829 were the most significant residues to target the FLT3 F691L
      which contribute most significantly to the binding energy with MZH29 and
      crenolanib. These interactions were found absent with quizartinib. Further free
      energy landscape analysis revealed that FLT3 F691L bound to MZH29 and crenolanib
      was more stable as compared to quizartinib.

PMID- 29336116
TI  - The retina of the collared peccary (Pecari tajacu): structure and function.
AB  - OBJECTIVE: To study retinal morphology and function in the collared peccary, an
      ungulate species distantly related to the domestic pig. ANIMAL STUDIES: Twenty
      captive peccaries anesthetized for routine health examinations. Procedures No
      abnormalities were noted on a complete ophthalmic examination. Fundi were
      examined ophthalmoscopically and photographed. The eyes of an individual that
      died of unrelated, nonocular reasons were studied histologically and by
      immunohistochemistry. Scotopic, mixed rod-cone, and photopic electroretinography
      (ERG) responses were recorded using the 'QuickRetCheck' (n = 6) and 'Dog
      diagnostic' (n = 5) protocols of the Handheld Multispecies ERG (HMsERG). RESULTS:
      The fundus of the peccary is atapetal, with varying amounts of pigmentation seen
      ophthalmoscopically, and histologically in the retinal pigment epithelium (RPE)
      and choroid. The retina is holangiotic with dichotomously branching vessels.
      These cross, and apparently loop on, the optic disk surface, but no venous circle
      was seen. Immunohistochemistry suggests a high concentration of cone
      photoreceptors with red/green cones being more abundant than blue cones. Rod ERG
      responses were very low with no evident dark adaptation. Mixed rod-cone and cone
      ERG response amplitudes were low compared to those of domestic pigs, but quite
      similar to those of minipigs. CONCLUSIONS: To the best of our knowledge, this
      study describes the collared peccary's retinal features for the first time. A
      comparison of our findings with data from other ungulate species shows some
      similarities between the peccary and pig retinas. Further studies are warranted
      to determine whether the peccary can be used alongside the pig as an animal model
      in retinal studies.

PMID- 29336117
TI  - Prussian Blue-Derived Iron Phosphide Nanoparticles in a Porous Graphene Aerogel
      as Efficient Electrocatalyst for Hydrogen Evolution Reaction.
AB  - Tailoring of new hydrogen evolution reaction (HER) electrocatalyst with earth
      abundant elements is important for large scale water splitting and hydrogen
      production. In this work, we present a simple synthetic method for incorporating
      iron phosphide (FeP) particles into three-dimensional (3D) porous graphene
      aerogel (GA) structure. The FeP formed in porous 3D GA (FeP/GA) is derived from
      electroactive Fe hexacyanoferrate (FeHCF). The advantage of incorporating FeP, in
      the porous 3D graphene network enables high accessibility for HER. As synthesized
      FeP/GA catalyst shows good electrocatalytic activity for HER in both acidic and
      alkaline solutions. The developed method can be useful for synthesizing metal
      hexacyanoferrate derived mono/bimetal phosphide catalyst in porous 3D graphene
      aerogels.

PMID- 29336118
TI  - Resveratrol Potently Counteracts Quercetin Starvation-Induced Autophagy and
      Sensitizes HepG2 Cancer Cells to Apoptosis.
AB  - SCOPE: Resveratrol (RSV) has been described as a potent antioxidant,
      antisteatotic, and antitumor compound, and it has also been identified as a
      potent autophagy inducer. On the other hand, quercetin (QCT) is a dietary
      flavonoid with known antitumor, anti-inflammatory, and antidiabetic effects.
      Additionally, QCT increases autophagy. To study the hypothetical synergistic
      effect of both compounds, we test the combined effect of QCT and RSV on the
      autophagy process in HepG2 cells. METHODS AND RESULTS: Autophagy is studied by
      western blotting, real-time RT-PCR, and cellular staining. Our results clearly
      indicate a bifunctional molecular effect of RSV. Both polyphenols are
      individually able to promote autophagy. Strikingly, when RSV is combined with
      QCT, it promotes a potent reduction of QCT-induced autophagy and influences
      proapoptotic signaling. CONCLUSION: RSV acts differentially on the autophagic
      process depending on the cellular energetic state. We further characterize the
      molecular mechanisms related to this effect, and we observe that AMP-activated
      protein kinase (AMPK) phosphorylation, heme oxygenase 1 (HO-1) downregulation,
      lysosomal membrane permeabilization (LMP), and Zinc (Zn2+ ) dynamics could be
      important modulators of such RSV-related effects and could globally represent a
      promising strategy to sensitize cancer cells to QCT treatment.

PMID- 29336119
TI  - Evaluations of UltraiQ software for objective ultrasound image quality assessment
      using images from a commercial scanner.
AB  - We evaluated a commercially available software package that uses B-mode images to
      semi-automatically measure quantitative metrics of ultrasound image quality, such
      as contrast response, depth of penetration (DOP), and spatial resolution
      (lateral, axial, and elevational). Since measurement of elevational resolution is
      not a part of the software package, we achieved it by acquiring phantom images
      with transducers tilted at 45 degrees relative to the phantom. Each measurement
      was assessed in terms of measurement stability, sensitivity, repeatability, and
      semi-automated measurement success rate. All assessments were performed on a GE
      Logiq E9 ultrasound system with linear (9L or 11L), curved (C1-5), and sector (S1
      5) transducers, using a CIRS model 040GSE phantom. In stability tests, the
      measurements of contrast, DOP, and spatial resolution remained within a +/-10%
      variation threshold in 90%, 100%, and 69% of cases, respectively. In sensitivity
      tests, contrast, DOP, and spatial resolution measurements followed the expected
      behavior in 100%, 100%, and 72% of cases, respectively. In repeatability testing,
      intra- and inter-individual coefficients of variations were equal to or less than
      3.2%, 1.3%, and 4.4% for contrast, DOP, and spatial resolution (lateral and
      axial), respectively. The coefficients of variation corresponding to the
      elevational resolution test were all within 9.5%. Overall, in our assessment, the
      evaluated package performed well for objective and quantitative assessment of the
      above-mentioned image qualities under well-controlled acquisition conditions. We
      are finding it to be useful for various clinical ultrasound applications
      including performance comparison between scanners from different vendors.

PMID- 29336120
TI  - The cognitive profile of Sotos syndrome.
AB  - Sotos syndrome is a congenital overgrowth disorder, associated with intellectual
      disability. Previous research suggests that Sotos syndrome may be associated with
      relative strength in verbal ability and relative weakness in non-verbal reasoning
      ability but this has not been explicitly assessed. To date, the cognitive profile
      of Sotos syndrome is unknown. Cognitive abilities of a large and representative
      sample of individuals with Sotos syndrome (N = 52) were assessed using the
      British Ability Scales (BAS3). The majority of participants had intellectual
      disability or borderline intellectual functioning. The cluster score profile
      analysis revealed a consistent verbal ability > non-verbal reasoning ability
      profile. Four specific criteria were proposed as the Sotos syndrome cognitive
      profile (SSCP): verbal ability > non-verbal reasoning ability; quantitative
      reasoning T-score or matrices T-score <20th percentile; quantitative reasoning T
      score < mean T-score; recognition of designs T-score or recognition of pictures T
      score > mean T-score. Of the 35 participants included in the profile analysis, 28
      met all four SSCP criteria, yielding a sensitivity of 0.8. The sensitivity of
      each of the SSCP criteria was >0.9. Individuals with Sotos syndrome display a
      clear and consistent cognitive profile, characterized by relative strength in
      verbal ability and visuospatial memory but relative weakness in non-verbal
      reasoning ability and quantitative reasoning. This has important implications for
      the education of individuals with Sotos syndrome.

PMID- 29336121
TI  - Inter- and intra-operator reliability in patient-specific template positioning
      for total hip arthroplasty. A cadaver study.
AB  - BACKGROUND: The implantation of the acetabular cup essentially determines the
      clinical outcome of total hip arthroplasty. To address this issue, the aim of
      this study was to build patient-specific instruments (PSIs) with various
      reference surfaces, followed by in vitro investigations to examine the inter- and
      intra-operator reliability as well as the overall precision of these patient
      specific templates. METHODS: Seven human hemi-pelvis specimens were used for this
      study. After a CT scan, PSIs with different imprint heights were created. The
      overall precision of the templates and the inter- and intra-operator
      reliabilities were calculated. RESULTS: Strong differences in precision between
      the PSI designs could be observed. The desired orientation of the acetabular cup
      could be adjusted with a precision of up to 1.55 degrees . CONCLUSION: Based on
      our results, we believe that the application of the PSI-based acetabular cup
      positioning in total hip arthroplasty procedures can potentially increase the
      precision of cup placement.

PMID- 29336122
TI  - LETTER TO EDITOR.

PMID- 29336123
TI  - Balance Assessment in Deaf Children and Teenagers Prior to and Post Capoeira
      Practice through the Berg Balance Scale.
AB  - INTRODUCTION: Hearing loss changes the functionality and body structure a
      disability that limits activity and restricts the participation of the individual
      in situations of daily life. It is believed that capoeira can help people with
      visual disabilities to minimize these deficits. BSE is a low specificity scale
      that evaluates objectively and functionally aspects of balance and risk of falls
      in the elderly and children, including the effect of environment on balance
      function. OBJECTIVE: The objective of the research is to analyze deaf children
      and adolescents prior to and post-practice of capoeira using the Berg Balance
      Scale (BBS). METHODS: Quantitative, clinical and observational studies. Twenty
      five deaf children between 10 and 16 years old of both genders were assessed. BBS
      was applied in two stages: before starting capoeira and after 6 months of
      training. The one-hour classes were held once a week for quantitative evaluation
      purposes. The subjects were divided and evaluated in two groups (10-13 years old
      and 14-16 years old). RESULTS: There was a significant statistical difference in
      BBS scores. The general group and the group of 10-13 years old (p = 0.0251)
      showed an increase in scores after practicing capoeira (p = 0.0039). There were
      no statistically significant differences in the group from 14 to 16 years of age
      (p = 0.0504). CONCLUSION: Using the Berg Balance Scale, it was possible to
      observe an improvement in the balance of the group of children and adolescents
      who practiced capoeira, and consequently, a decrease in the risk of falling.

PMID- 29336124
TI  - Masking Treatment and its Effect on Tinnitus Parameters.
AB  - OBJECTIVE: Tinnitus is described as the perception of sound without any external
      acoustic stimulation. Any pathology of auditory pathways or any system of the
      human body may result with tinnitus. The pathophysiology of tinnitus accompanying
      the disorders of auditory system is not fully understood and there is not any
      particular effective treatment method has been specified. Tinnitus masking
      therapy has been reported as an effective treatment modality in the treatment of
      tinnitus. In this study, the results of tinnitus masking treatment on the
      parameters were evaluated prospectively. PATIENTS AND METHODS: Patients with
      normal physical examination was enrolled in the study. Blood tests (complete
      blood count, biochemical analysis of lipid profile, and thyroid hormones), pure
      tone audiometry, tympanometric measurement of the middle ear pressure and
      stapedial reflexes were performed, Sixty six patients with normal results of
      blood tests and normal hearing thresholds with type A tympanogram were included.
      Tinnitus sufferers questionnaires (socio-demographics, clinical information,
      Tinnitus Handicap Inventory (THI), Beck Depression Inventory (BDI) was filled,
      audiological tests were performed, tinnitus parameters (frequency, intensity,
      minimal masking levels, residual inhibition) were measured. After four weeks of
      the treatment the questionnaires were repeated. RESULTS: Masking treatment for
      tinnitus patients resulted with significant decrease in Tinnitus Handicap
      Inventory and VAS scores. After four weeks of the masking treatment the
      questionnaire was repeated. Twenty patients did not respond to treatment.
      CONCLUSION: Masking therapy is one of the most effective methods of treatment for
      tinnitus patients. Masking therapy, that is not invasive and cost-effective has
      an important place in the treatment of tinnitus. Especially in a short time
      provides a significant reduction in tinnitus parameters.

PMID- 29336125
TI  - Association of Chronic Subjective Tinnitus with Neuro- Cognitive Performance.
AB  - INTRODUCTION: Chronic subjective tinnitus is associated with cognitive
      disruptions affecting perception, thinking, language, reasoning, problem solving,
      memory, visual tasks (reading) and attention. OBJECTIVE: To evaluate existence of
      any association between tinnitus parameters and neuropsychological performance to
      explain cognitive processing. MATERIALS AND METHODS: Study design was
      prospective, consisting 25 patients with idiopathic chronic subjective tinnitus
      and gave informed consent before planning their treatment. Neuropsychological
      profile included (i) performance on verbal information, comprehension, arithmetic
      and digit span; (ii) non-verbal performance for visual pattern completion
      analogies; (iii) memory performance for long-term, recent, delayed-recall,
      immediate-recall, verbal-retention, visualretention, visual recognition; (iv)
      reception, interpretation and execution for visual motor gestalt. Correlation
      between tinnitus onset duration/ loudness perception with neuropsychological
      profile was assessed by calculating Spearman's coefficient. RESULTS: Findings
      suggest that tinnitus may interfere with cognitive processing especially
      performance on digit span, verbal comprehension, mental balance, attention &
      concentration, immediate recall, visual recognition and visual-motor gestalt
      subtests. Negative correlation between neurocognitive tasks with tinnitus
      loudness and onset duration indicated their association. Positive correlation
      between tinnitus and visual-motor gestalt performance indicated the brain
      dysfunction. CONCLUSION: Tinnitus association with non-auditory processing of
      verbal, visual and visuo-spatial information suggested neuroplastic changes that
      need to be targeted in cognitive rehabilitation.

PMID- 29336126
TI  - Effects of Smoking on Eustachian Tube and Hearing.
AB  - OBJECTIVE: The purpose of this study was to evaluate the effect of tobacco use on
      the Eustachian tube and inner ear function. STUDY DESIGN: Case-control study.
      SUBJECTS AND SETTINGS: Thirty-one nonsmoking volunteers and 34 smoking subjects
      recruited in an University Hospital, submitted to an audiological evaluation
      including pure tone audiometry, basal tympanogram, stapedial reflexes analysis,
      and nine-step eustachian tube (ET) function test. RESULTS: Pure Tone Average
      (PTA) threshold at all frequencies tested was 12.5 dB in smokers and 3.7 in
      nonsmoking subjects. Nine smokers (27%) presented some degree of hearing loss
      versus none in the nonsmoker group. Linear regression analysis showed a higher
      degree of sensorineural hearing loss with age in smokers. Among the smokers, 20
      subjects (59%) presented an impaired tubal function for the nine-step
      inflation/deflation tympanometric test, while only 6 (19%) subjects in the group
      of nonsmokers showed a tubal dysfunction. CONCLUSION: Tobacco use may reduce the
      ability to hear, mainly causing a sensorineural hearing loss for higher
      frequencies. We also found the presence of a high number of smokers suffering
      from tubal dysfunction. This has an important clinical relevance, not only
      because smoking increases the incidence of middle ear diseases, but also because
      tubal dysfunction may cause nonspecific symptoms characterised by ear fullness
      and difficulties in middle ear equalisation.

PMID- 29336127
TI  - Popularity and Harms of Aural Foreign Bodies: A Descriptive Study of Patients in
      Baqiyatallah University Hospital, Tehran, Iran.
AB  - OBJECTIVE: To evaluate the prevalence of external ear complications among Iranian
      aural foreign body users attending to otolaryngology clinic of our hospital.
      METHODS: In this cross-sectional study patients attending to Otolaryngology
      clinics of Baqiyatallah hospital were enrolled regardless of their age, gender
      and reason of attending. Patients between 15 and 60 years of age were included in
      the present study. Those with positive history of chronic ear diseases, ear
      surgery, congenital ear disorders, trauma to ear or head and neck region or shock
      wave trauma were excluded from the study. Demographic information as well as data
      on chief complaint, educational level, frequency and type of used foreign body
      and findings of physical examination and Otoscopy by a single otolaryngologist
      were recorded in a predesigned checklist. RESULTS: Eventually 362 patients (232
      male and 130 female) with a mean age of 40.32 +/- 16.90 years underwent analysis.
      Of all patients 244 (67.2%) were using a kind of aural foreign body frequently
      and Cotton bud was the most popular (63.5%) used foreign body among patients.
      Drying ear canal was the most common (54.9%) reason of using AFBs among study
      individuals followed by itching (29.5%) and pyorrhea (11.06%). Also 11 (4.5%)
      patients were using AFBs as a habit with no specific reason. Itching was the most
      prevalent symptom reported by both aural foreign body users (78%) and non-users
      (45.5%); however it was significantly higher among AFB users (p = 0.026). Also
      hearing loss was significantly more reported by AFB users (p = 0.033). A majority
      of patients had normal physical examination in both AFB users and non-users
      group. Inflammation of ear canal was significantly more detected in AFB users (p
      = 0.004). In addition, rate of right ear wax impaction was higher among AFB users
      (p = 0.016). CONCLUSION: In conclusion we realized that 67.2% of patients
      attending to Otolaryngology clinic of our hospital were using a kind of aural
      foreign bodies and itching was the most common chief complaint of these patients.

PMID- 29336128
TI  - The Effect of PRP-enriched Gelfoam on Chronic Tympanic Membrane Perforation: A
      Double-blind Randomized Clinical Trial.
AB  - OBJECTIVE: To evaluate the effect of PRP-enriched gelfoam on the healing of
      chronic TM perforation in comparison with gelfoam alone. METHODS: In this double
      blind randomized clinical trial Patients with chronic tympanic membrane were
      randomly allocated to two groups; intervention group underwent tympanoplasty with
      platelet rich plasma (PRP)- enriched gel foams and control group underwent
      operation with conventional gel foams alone. Patients information was recorded 4
      and 12 months after surgery. RESULTS: Eventually 24 patients (12 males and 12
      females) with a mean age of 43.33 +/- 12.34 years in intervention and 41.33 +/-
      10.02 years in control group underwent analysis (p = 0.667). Complete TM healing
      was seen in 8 (66.67%) patients in intervention group and 3 (25%) patients in
      control group three months after intervention (p = 0.031, OR = 5.98). CONCLUSION:
      Addition of PRP to conventional gelfoams used in TM perforation repair increases
      the complete healing rate of TM perforation with less morbidity and
      complications.

PMID- 29336129
TI  - Somatic Tinnitus.
AB  - Modulation of tinnitus characteristics such as pitch and loudness has been
      extensively described following movements of the head, neck and limbs, vertical
      or horizontal eye gaze, pressure on myofascial trigger points, cutaneous
      stimulation of the hands, electrical stimulation of the median nerve, and
      transcranial direct current stimulation. Modulation of tinnitus follows complex
      interactions between auditory and somatosensory afferents and can be favored by
      underlying somatic disorders. When tinnitus appears to be preceded or strictly
      linked to a somatic disorder, and therefore related to problems of the
      musculoskeletal system rather than of the ear, it is defined somatic tinnitus. A
      correct diagnosis and treatment of somatic disorders underlying tinnitus play a
      central role for a correct management of somatic tinnitus. However, the
      identification of somatic tinnitus may be complex in some cases. In this paper,
      after a general review of the current evidences for somatic tinnitus available in
      the literature, we present and discuss some cases of patients in which somatic
      modulation of tinnitus played a role-although different from case to case-in
      their tinnitus, describing the diagnostic and therapeutic approaches followed in
      each individual case and the results obtained, also highlighting unexpected
      findings and pitfalls that may be encountered when approaching somatic tinnitus
      patients.

PMID- 29336130
TI  - Comparison of Three Types of Mesenchymal Stem Cells (Bone Marrow, Adipose Tissue,
      and Umbilical Cord-Derived) as Potential Sources for Inner Ear Regeneration.
AB  - In this review, we compared the potential of mesenchymal stem cells derived from
      bone marrow, adipose tissue and umbilical cord as suitable sources for
      regeneration of inner ear hair cells and auditory neurons. Our intensive
      literature search indicates that stem cells in some of adult mammalian tissues,
      such as bone marrow, can generate new cells under physiological and pathological
      conditions. Among various types of stem cells, bone marrow-derived mesenchymal
      stem cells are one of the most promising candidates for cell replacement therapy.
      Mesenchymal stem cells have been reported to invade the damaged area, contribute
      to the structural reorganization of the damaged cochlea and improve incomplete
      hearing recovery. We suggest that bone marrow-derived mesenchymal stem cells
      would be more beneficial than other mesenchymal stem cells.

PMID- 29336131
TI  - Vestibular Schwannoma and Ipsilateral Endolymphatic Hydrops: An Unusual
      Association.
AB  - Vestibular schwannoma and endolymphatic hydrops are two conditions that may
      present with similar audio-vestibular symptoms. The association of the two in the
      same patient represents an unusual finding that may lead clinicians to errors and
      delays in diagnosis and clinical management of affected subjects. We discuss the
      case of a patient with an intrameatal vestibular schwannoma reporting symptoms
      suggestive for ipsilateral endolymphatic hydrops. The patient presented with
      fluctuating hearing loss, tinnitus, and acute rotatory vertigo episodes, and
      underwent a full audiological evaluation and imaging of the brain with contrast
      enhanced Magnetic Resonance Imaging. Clinical audio-vestibular and radiological
      examination confirmed the presence of coexisting vestibular schwannoma and
      endolymphatic hydrops. Hydrops was treated pharmacologically; vestibular
      schwannoma was monitored over time with a wait and scan protocol through
      conventional MRI. The association of vestibular schwannoma and endolymphatic
      hydrops is rare, but represents a possible finding in clinical practice. It is
      therefore recommended investigating the presence of inner ear disorders in
      patients with vestibular schwannoma and, similarly, to exclude the presence of
      this condition in patients with symptoms typical of inner ear disorders.

PMID- 29336132
TI  - Auditory System Synchronization and Cochlear Function in Patients with Normal
      Hearing With Tinnitus: Comparison of Multiple Feature with Longer Duration and
      Single Feature with Shorter Duration Tinnitus.
AB  - OBJECTIVE: To observe cochlear and brainstem function in normal hearing ears with
      tinnitus using DPOAE and ABR audiometry. DESIGN: Case-control study. SAMPLE SIZE:
      Included 60 normal hearing male patients with age less than 45 years; control
      group consisted of 30 patients without tinnitus and the study group consisted of
      those with unilateral tinnitus of at least 6 month duration. Pure tone
      audiometry, tinnitus matching (pitch & loudness), DPOAE (SNR & Amplitude) and ABR
      results of absolute latency of wave I, III and V, with IPL difference of I-III,
      III-V & I-V, and ILD-V were investigated. RESULTS: SNR and amplitude value of
      DPOAE were significantly different between tinnitus ears and without tinnitus
      ears. Abnormal prolonged absolute latencies of peak I, III, V suggesting presence
      of hearing loss above 8 kHz and significant difference of only IPL III-V in the
      tinnitus ear suggesting of upper brain steam lesion in tinnitus patients were
      found. The IPL of III-V and ILD-V findings were significantly different in longer
      duration with multiple features (more than one type of pitch) than shorter
      duration with single feature tinnitus. Thus whole brainstem function has
      significant relationship with the presence of tinnitus, longer duration with
      multiple nature of tinnitus perception. CONCLUSION: Abnormal OAE and ABR results
      were present in patients with tinnitus. It was more prominent in patients with
      longer duration with multiple features of tinnitus perception.

PMID- 29336133
TI  - Effects of Tinnitus Retraining Therapy with Different Colours of Sound.
AB  - BACKGROUND: In Tinnitus Retraining Therapy (TRT) sound stimulation is
      conventionally performed with low-level broadband sound generators; since the
      patient has to receive it for many hours in a day, it is important that the sound
      is tolerable and agreeable to the patient. A clinical trial was undertaken to
      evaluate the effect of different colour sound generators on tinnitus. The colour
      of a sound refers to the power spectrum of the signal. The sound generators used
      in this study provide the option to choose the preferred or most acceptable sound
      among white, red and pink noise. METHODS AND FINDINGS: Changes in Tinnitus
      Handicap Inventory and Numeric Rating Scales were measured in 20 patients after 3
      and 6 months following the fitting of ear-level multi-colour sound generators.
      The outcomes were compared to a similar group of 20 participants receiving the
      same management except through conventional white noise sound generators.
      Significant improvements were obtained in both groups following 3 and 6 months
      after fitting. No significant difference was found between the two groups using
      one or the other type of sound. Two thirds of the patient preferred white noise,
      making it the most appealing amongst the options. The rest of the patients
      indicated red noise as the preferred sound given that it reminded them of
      soothing noises like shower or rainfall. No one chose pink noise. CONCLUSIONS:
      TRT with different colour sound generators is effective in reducing the
      discomfort caused by tinnitus in normal hearing patients. Enabling the patients
      to choose their preferred sound after short trial periods achieved higher patient
      satisfaction. This practice could help tailor individualized treatment for each
      patient.

PMID- 29336134
TI  - Treatment of Tinnitus: A Scoping Review.
AB  - BACKGROUND: Tinnitus is a perception of an auditory sensation without the
      presence of an external sound. It has devastating impact on the quality of life
      and psychosocial aspect of the sufferer. Mechanisms of tinnitus not clear;
      however, its management include counselling, hearing aids, tinnitus masking,
      relaxation therapy, cognitive behaviour therapy and tinnitus retraining therapy.
      OBJECTIVE: To conduct a scoping review to explore the role of counselling,
      hearing aids, tinnitus masking, relaxation therapy, cognitive-behavioural therapy
      and tinnitus retraining therapy in India. To also provide an overview of efficacy
      of these approaches in tinnitus management. RESEARCH DESIGN: Scoping review.
      STUDY SAMPLE: Experimental studies, follow-up assessments, and reviews assessing
      tinnitus treatment approaches were identified as a result of an electronic
      database met search. RESULTS: The evidence suggests that all tinnitus management
      programs have their unique benefits in the treatment of tinnitus. Given the
      confounding variables that include length of therapy, tinnitus severity and
      subject population, the overall level of evidence is equivocal. Nonetheless, the
      efficacy of CBT appears reasonably established and combined approach (masking +
      counselling + attention diversion) appears to be most promising for audiologists
      for future tinnitus management. A common ground of therapeutic elements was
      established and evidence was found to be robust enough to guide clinical
      practice. CONCLUSION: The use of more robust methodology with well-defined
      control groups, as well as randomization of clinical trials in future studies
      would increase the quality of evidence in the study of tinnitus management.
      CLINICAL RECOMMENDATION: Combined therapies (masking + counselling + attention
      diversion) appear more appropriate in the treatment of tinnitus as the evidence
      is not sufficient to support a specific treatment method.

PMID- 29336135
TI  - A Randomized, Placebo-Controlled, Double-Blind, Parallel Groups Study Evaluating
      the Performance and Safety of a Steady State Coherent Biomodulator Patch in the
      Treatment of Subjective Tinnitus.
AB  - OBJECTIVE: The objectives of this study were to evaluate the performance and
      safety of an innovative passive light photon driven microscopic biomodulator
      patch as an alternative medical device for tinnitus relief. MATERIALS AND
      METHODS: Eighty-two (82) patients were randomized to receive either an active
      (biomodulator) patch or a placebo patch, for a 3-week treatment period. Patch
      performance (evaluated with questionnaires related to tinnitus and quality-of
      life) and safety were assessed after 3 weeks of treatment (Week 3) and at a
      follow-up visit 4-weeks after end of treatment (Week 7). RESULTS: The
      biomodulator patch was safe and well-tolerated and was efficacious, with
      significant difference (p < 0.05) between the groups at Week 7; active patch had
      30% responders compared to 10% for placebo, measured as a decrease from baseline
      in at least 2 points in tinnitus annoyance visual analogue scale (VAS, 0-10).
      Tinnitus handicap inventory (THI, 0-100) improved by mean -16 points
      significantly (p = 0.0005) for the active responder group, but with no
      statistically significant changes for the placebo group or between the groups.
      Well-being questionnaire also improved for the active responder group, but not
      statistically significant. The placebo responder group did not improve in well
      being. Other tinnitus related symptoms did not show significant changes. There
      was no statistically significant difference in performance between the active
      (biomodulator) and placebo groups directly at the end of treatment (Week 3).
      CONCLUSION: In a cost-risk-benefit rationale according to this study it can be
      reasonable to recommend the biomodulator patch for treatment of tinnitus.
      Improvements were shown at Week 7 (4 weeks after the end of treatment period).

PMID- 29336136
TI  - International Clinical Protocol on Vestibular Disorders (Dizziness).
AB  - 26-28 May at 43 Congress of Neurootological and Equilibriometric Society
      (Budapest, Hungary) International Clinical Protocol on Vestibular Disorders
      (Dizziness) being discussed and accepted as Consensus Document. Cochrane reports
      estimates that dizziness has prevalence of 22.9% in the last 12 months and an
      incidence of 3.1%. Only 1.8% of adults consulted a physician in the last 12
      months. Cochrane reviews suggest that the evidence base for dizziness evaluation
      is weak, thus necessitates the creation of evidence-based document. Protocol is
      based at the new concept of vestibular system, which involves the vestibular
      peripheral sensors, space orientation tetrad, vestibular presentations in the
      brain cortex and vestibular effectory projections in the brain. Labyrinth
      consists of sensors, for which six modalities are adequate: 1. acceleration, 2.
      gravitation, 3. low frequency whole-body vibration, 4. Infrasound, 5. magnetic
      impulse, 6. metabolic changes. Vestibular system from rhomboid fosse gets the
      inputs from visual, acoustic, somatosensory organs, integrating them and forming
      space perception and orientation. Interaction with space is realized through
      sensory, motor, vegetative and limbic projections. So, vestibular disturbances
      may manifest as paropsia, tinnitus, numbness. Vestibular evoked potentials (not
      VEMP) and craniocorpography have highest sensitivity (90% and more). As
      vestibular dysfunction has recurrent character patients need monitoring.

PMID- 29336137
TI  - In Vitro Differentiation of Human Bone Marrow Mesenchymal Stem Cells to Hair
      Cells Using Growth Factors.
AB  - OBJECTIVE: In this study, we attempted to differentiated human bone marrow
      derived mesenchymal stem cells (hBMSCs) to auditory hair cells using growth
      factors. METHODS: Retinoic acid (RA), basic fibroblast growth factor (bFGF), and
      epidermal growth factor (EGF) were added to hBMSCs cell culture medium. The cells
      were evaluated morphologically and the expression of SOX2, POU4F3, MYO7A, and
      Calretinin at mRNA level and ATOH1 mRNA and protein expression. RESULTS: After
      treatment with the growth factors, the morphology of the cells did not change,
      but evaluation of gene expression at the mRNA level increased the expression of
      the ATOH1, SOX2, and POU4F3 markers. Growth factors increased the expression of
      ATOH1 at the protein level. The expression of calretinin showed decreased and
      MYO7A no significant change in expression. CONCLUSION: hBMSCs have the potential
      to differentiate to hair cell-like using the RA, bFGF, and EGF.

PMID- 29336138
TI  - Psycho acoustical Measures in Individuals with Congenital Visual Impairment.
AB  - INTRODUCTION: In congenital visual impaired individuals one modality is impaired
      (visual modality) this impairment is compensated by other sensory modalities.
      There is evidence that visual impaired performed better in different auditory
      task like localization, auditory memory, verbal memory, auditory attention, and
      other behavioural tasks when compare to normal sighted individuals. OBJECTIVE:
      The current study was aimed to compare the temporal resolution, frequency
      resolution and speech perception in noise ability in individuals with congenital
      visual impaired and normal sighted. METHODS: Temporal resolution, frequency
      resolution, and speech perception in noise were measured using MDT, GDT, DDT,
      SRDT, and SNR50 respectively. Twelve congenital visual impaired participants with
      age range of 18 to 40 years were taken and equal in number with normal sighted
      participants. All the participants had normal hearing sensitivity with normal
      middle ear functioning. RESULTS: Individual with visual impairment showed
      superior threshold in MDT, SRDT and SNR50 as compared to normal sighted
      individuals. This may be due to complexity of the tasks; MDT, SRDT and SNR50 are
      complex tasks than GDT and DDT. CONCLUSION: Visual impairment showed superior
      performance in auditory processing and speech perception with complex auditory
      perceptual tasks.

PMID- 29336139
TI  - Smart Self-Assembled Nanosystem Based on Water-Soluble Pillararene and Rare-Earth
      Doped Upconversion Nanoparticles for pH-Responsive Drug Delivery.
AB  - Exploring novel drug delivery systems with good stability and new structure to
      integrate pillararene and upconversion nanoparticles (UCNPs) into one system
      continues to be an important challenge. Herein, we report a novel preparation of
      a supramolecular upconversion nanosystem via the host-guest complexation based on
      carboxylate-based pillar[5]arene (WP5) and 15-carboxy-N,N,N-trialkylpentadecan-1
      ammonium bromide (1)-functionalized UCNPs to produce WP5?1-UCNPs that can be
      loaded with the chemotherapeutic drug doxorubicin (DOX). Importantly, the WP5 on
      the surface of the drug-loaded nanosystem can be efficiently protonated under
      acidic conditions, resulting in the collapse of the nanosystem and drug release.
      Moreover, cellular uptake confirms that the nanosystem can enter human cervical
      cancer (HeLa) cells, resulting in drug accumulation in the cells. More
      importantly, cytotoxicity experiments demonstrated the excellent biocompatibility
      of WP5?1-UCNPs without loading DOX and that the nanosystem DOX-WP5?1-UCNPs
      exhibited an ability of killing HeLa cells effectively. We also investigated
      magnetic resonance imaging and upconversion luminescence imaging, which may be
      employed as visual imaging agents in cancer diagnosis and treatment. Thus, in the
      present work, we show a simple yet powerful strategy to combine UCNPs and
      pillar[5]arene to produce a unified nanosystem for dual-mode bioimaging-guided
      therapeutic applications.

PMID- 29336140
TI  - Synthesis of Cisplatin(IV) Prodrug-Tethered CuFeS2 Nanoparticles in Tumor
      Targeted Chemotherapy and Photothermal Therapy.
AB  - In this study, for the first time, CuFeS2 nanocrystals were successfully prepared
      through a facile noninjection-based synthetic strategy, by reacting Cu and Fe
      precursors with dodecanethiol in a 1-octadecene solvent. This one-pot
      noninjection strategy features easy handling, large-scale production, and high
      synthetic reproducibility. Following hyaluronic acid (HA) encapsulation, CuFeS2
      nanocrystals coated with HA (CuFeS2@HA) not only readily dispersed in water and
      showed improved biocompatibility but also possessed a tumor-specific targeting
      ability of cancer cells bearing the cluster determinant 44 (CD44) receptors. The
      encapsulated CuFeS2@HA showed broad optical absorbance from the visible to the
      near-infrared (NIR) region and high photothermal conversion efficiencies of about
      74.2%. They can, therefore, be utilized for the photothermal ablation of cancer
      cells with NIR light irradiation. In addition, toxicity studies in vitro (B16F1
      and HeLa) and in vivo (zebrafish embryos), as well as in vitro blood
      compatibility studies, indicated that CuFeS2@HA show low cytotoxicity at the
      doses required for photothermal therapy. More importantly, CuFeS2@HA can be used
      as delivery vehicles for chemotherapy cisplatin(IV) prodrug forming CuFeS2@HA
      Pt(IV). Their release profile revealed pH- and glutathione-mediated drug release
      from CuFeS2@HA-Pt(IV), which may minimize the side effects of the drug to normal
      tissues during therapy. Subsequent in vitro experiments confirmed that the use of
      CuFeS2@HA-Pt(IV) provides an enhanced and synergistic therapeutic effect compared
      to that from the use of either chemotherapy or photothermal therapy alone.

PMID- 29336141
TI  - Label-Free Optical Biodetection of Pathogen Virulence Factors in Complex Media
      Using Microtoroids with Multifunctional Surface Functionality.
AB  - Early detection of pathogens or their virulence factors in complex media has a
      key role in early diagnosis and treatment of many diseases. Nanomolar and
      selective detection of Exotoxin A, which is a virulence factor secreted from
      Pseudomonas aeruginosa in the sputum of Cystic Fibrosis (CF) patients, can pave
      the way for early diagnosis of P. aeruginosa infections. In this study, we
      conducted a preliminary study to demonstrate the feasibility of optical
      biodetection of P. aeruginosa Exotoxin A in a diluted artificial sputum mimicking
      the CF respiratory environment. Our surface engineering approach provides an
      effective biointerface enabling highly selective detection of the Exotoxin A
      molecules in the complex media using monoclonal anti-Exotoxin A functionalized
      microtoroids. The highly resilient microtoroid surface toward other constituents
      of the sputum provides Exotoxin A detection ability in the complex media by
      reproducible measurements. In this study, the limit-of-detection of Exotoxin A in
      the complex media is calculated as 2.45 nM.

PMID- 29336142
TI  - Smart Dual Quenching Strategy Enhances the Detection Sensitivity of Intracellular
      Furin.
AB  - Development of sensitive fluorescence "Turn-On" strategies for imaging enzyme
      activity in living cells is of disease-diagnostic importance but remains
      challenging. Herein, by employing a click condensation reaction and rational
      design of a single quenched probe Cys(StBu)-Lys(Gly-Lys(DABCYL)-Gly-Gly-Arg-Arg
      Val-Arg-Gly-FITC)-CBT (1), we developed a "smart" dual quenching strategy and
      applied it to detect intracellular furin activity with enhanced sensitivity. At
      physiological conditions, 1 was subjected to reduction-controlled condensation
      reaction to form 1-NPs and its fluorescence intensity further dropped to 1/2.8 of
      its original. Upon furin cleavage in vitro, the dual quenched 1-NPs had
      fluorescence "Turn-On" contrast 11-fold more than that of single quenched control
      probe FITC-Gly-Arg-Val-Arg-Arg-Gly-Gly-Lys(DABCYL)-Gly-OH (1-P). Live cell
      imaging results indicated that 1 showed fluorescence "Turn-On" contrast 6.3-fold
      of that of 1-P for sensing intracellular furin activity. We envision that, by
      replacing the RVRR substrate with other enzyme-cleavable ones, our versatile
      "smart" dual quenching strategy could be easily adjusted for the detection (or
      imaging) of other intracellular enzymes' activity with enhanced sensitivity.

PMID- 29336143
TI  - Water-Soluble Fluorescent Probe with Dual Mitochondria/Lysosome Targetability for
      Selective Superoxide Detection in Live Cells and in Zebrafish Embryos.
AB  - A novel water-soluble fluorescein-based fluorescent probe for superoxide
      detection was developed. The probe is fairly stable under neutral and acidic
      conditions. It can be used to detect superoxide both in solution with the
      detection limit of 2.2 MUM and in living cells. Cell imaging experiments
      indicated that such a probe displayed good cell penetration and O2*- could be
      detected with PMA-stimulated HepG2 cells in both mitochondria and lysosome. Such
      a probe is the first dual mitochondria- and lysosome- targetable fluorescent
      chemodosimeter. Additionally, O2*- in intact live zebrafish embryos was
      successfully visualized under PMA-stimulated conditions, and the possible
      detection mechanism was studied as well.

PMID- 29336144
TI  - Nanostructured Peptidotoxins as Natural Pro-Oxidants Induced Cancer Cell Death
      via Amplification of Oxidative Stress.
AB  - Melittin (Mel), one of the host defense peptides derived from the venom of
      honeybees, demonstrates substantial anticancer properties, which is attributed to
      augmenting reactive oxygen species (ROS) generation. However, little has been
      reported on its pro-oxidation capacity in cancer oxidation therapy. In this
      study, an ROS amplifying nanodevice was fabricated through direct complexation of
      two natural pro-oxidants, Mel and condensed epigallocatechin gallate (pEGCG). The
      obtained nanocomplex (NC) was further covered with phenylboronic acid derivatized
      hyaluronic acid (pHA) through the ROS-responsive boronate ester coordination bond
      to produce pHA-NC. Upon undergoing receptor-mediated endocytosis into cancer
      cells, the inner cores of pHA-NC will be partially uncovered once pHA corona is
      degraded by hyaluronidase and will then escape from the lysosome by virtue of
      cytolytic Mel. The elevated ROS level in the tumor cytoplasm can disrupt the
      boronate ester bond to facilitate drug release. Both Mel and pEGCG could
      synergistically amplify oxidative stress and prolong ROS retention in cancer
      cells, leading to enhanced anticancer efficacy. This ROS cascade amplifier based
      on selective coordination bond and inherent pro-oxidation properties of natural
      ingredients could detect and elevate intracellular ROS signals, potentiating to
      move the tumor away from its homeostasis and make the tumor vulnerable. Compared
      to previously reported chemosynthetic pro-oxidants, the ROS self-sufficient
      system, fully composed of natural medicine, from this study provides a new
      insight in developing cancer oxidation therapy.

PMID- 29336145
TI  - T1-Mediated Nanosensor for Immunoassay Based on an Activatable MnO2 Nanoassembly.
AB  - Current magnetic relaxation switching (MRS) sensors for detection of trace
      targets in complex samples still suffer from limitations in terms of relatively
      low sensitivity and poor stability. To meet this challenge, we develop a
      longitudinal relaxation time (T1)-based nanosensor by using Mn2+ released from
      the reduction of a MnO2 nanoassembly that can induce the change of T1, and thus
      can greatly improve the sensitivity and overcome the "hook effect" of
      conventional MRS. Through the specific interaction between antigen and the
      antibody-functionalized MnO2 nanoassembly, the T1 signal of Mn2+ released from
      the nanoassembly is quantitatively determined by the antigen, which allows for
      highly sensitive and straightforward detection of targets. This approach broadens
      the applicability of magnetic biosensors and has great potential for applications
      in early diagnosis of disease biomarkers.

PMID- 29336146
TI  - Coordination-Triggered Hierarchical Folate/Zinc Supramolecular Hydrogels Leading
      to Printable Biomaterials.
AB  - Printable hydrogels desired in bioengineering have extremely high demands on
      biocompatibility and mechanic strength, which can hardly be achieved in
      conventional hydrogels made with biopolymers. Here, we show that on employment of
      the strategy of coordination-triggered hierarchical self-assembly of naturally
      occurring small-molecule folic acid, supramolecular hydrogels with robust
      mechanical elastic modulus comparable to synthetic double-network polymer gels
      can be made at concentrations below 1%. A sequence of hierarchical steps are
      involved in the formation of this extraordinary hydrogel: petrin rings on folate
      form tetramers through hydrogen bonding, tetramers stack into nanofibers by pi-pi
      stacking, and zinc ions cross-link the nanofibers into larger-scale fibrils and
      further cross-link the fibril network to gel water. These supramolecular
      qualities endow the hydrogel with shear-thinning and instant healing ability,
      which makes the robust gel injectable and printable into various three
      dimensional structures. Owing to the excellent biocompatibility, the gel can
      support cells three-dimensionally and can be used as an ideal carrier for imaging
      agent (Gd3+), as well as chemodrugs. In combination with its easy formation and
      abundant sources, this newly discovered metallo-folate supramolecular hydrogel is
      promising in various bioengineering technological applications.

PMID- 29336147
TI  - Urolithins Attenuate LPS-Induced Neuroinflammation in BV2Microglia via MAPK, Akt,
      and NF-kappaB Signaling Pathways.
AB  - Emerging data suggest that urolithins, gut microbiota metabolites of
      ellagitannins, contribute toward multiple health benefits attributed to
      ellagitannin-rich foods, including walnuts, red raspberry, strawberry, and
      pomegranate. However, there is limited data on whether the potential
      neuroprotective effects of these ellagitannin-rich foods are mediated by
      urolithins. Herein, we evaluated the potential mechanisms of
      antineuroinflammatory effects of urolithins (urolithins A, B, and C; 8-methyl-O
      urolithin A; and 8,9-dimethyl-O-urolithin C) in BV2 murine microglia in vitro.
      Nitrite analysis and qRT-PCR suggested that urolithins A and B reduced NO levels
      and suppressed mRNA levels of pro-inflammatory genes of TNF-alpha, IL-6, IL
      1beta, iNOS, and COX-2 in LPS-treated microglia. Western blot revealed that
      urolithins A and B decreased phosphorylation levels of Erk1/2, p38 MAPK, and Akt,
      prevented IkappaB-alpha phosphorylation and degradation, and inhibited NF-kappaB
      p65 subunit phosphorylation and nuclear translocation in LPS-stimulated
      microglia. Our results indicated that urolithins A and B attenuated LPS-induced
      inflammation in BV2 microglia, which may be mediated by inhibiting NF-kappaB,
      MAPKs (p38 and Erk1/2), and Akt signaling pathway activation. The
      antineuroinflammatory activities of urolithins support their role in the
      potential neuroprotective effects reported for ellagitannin-rich foods warranting
      further in vivo studies on these ellagitannin gut microbial derived metabolites.

PMID- 29336148
TI  - Logic Catalytic Interconversion of G-Molecular Hydrogel.
AB  - By incorporating hemin into G-quadruplex (G4) during cation-templated self
      assembly between guanosine and KB(OH)4, we have constructed an artificial enzyme
      hydrogel (AEH)-based system for the highly sensitive and selective detection of
      Pb2+. The sensing strategy is based on a Pb2+-induced decrease in AEH activity.
      Because of the higher efficiency of Pb2+ for stabilizing G4 compared with K+, the
      Pb2+ ions substitute K+ and trigger hemin release from G4, thus giving rise to a
      conformational interconversion accompanied by the loss of enzyme activity. The
      Pb2+-induced catalytic interconversion endows the AEH-based system with high
      sensitivity and selectivity for detecting Pb2+. As a result, the AEH-based system
      shows an excellent response for Pb2+ in the range from 1 pM to 50 nM with a limit
      of detection of ~0.32 pM, which is much lower than that of the previously
      reported G4-DNAzyme. We also demonstrate that this AEH-based system exhibits high
      selectivity toward Pb2+ over other metal ions. Furthermore, two two-input INHIBIT
      logic gates have been constructed via switching of the catalytic interconversion
      induced by K+ and Pb2+ or K+ and pH. Given its versatility, this AEH-based system
      provides a novel platform for sensing and biomolecular computation.

PMID- 29336149
TI  - Molecular Imprinting Based Hybrid Ratiometric Fluorescence Sensor for the Visual
      Determination of Bovine Hemoglobin.
AB  - We describe a simple and effective strategy to construct a molecular imprinting
      ratiometric fluorescence sensor (MIR sensor) for the visual detection of bovine
      hemoglobin (BHb) used as a model protein. The sensor was prepared by simply
      mixing the solution of green and red CdTe quantum dots (QDs), which were embedded
      in core-shell structured molecularly imprinted polymers and silica nanoparticles,
      respectively. The resultant hybrid MIR sensor can selectively bind with BHb and
      thus quench the fluorescence of the green QDs, while the red QDs wrapped with
      silica are insensitive to BHb with the fluorescence intensity unchanged. As a
      result, a continuous obvious fluorescence color change from green to red can be
      observed by naked eyes, with the detection limit of 9.6 nM. Moreover, the MIR
      sensor was successfully applied to determine BHb in bovine urine samples with
      satisfactory recoveries at three spiking levels ranging from 95.7 to 101.5%,
      indicating great potential application for detecting BHb in real samples. This
      strategy of using different fluorescence emission materials incorporated to
      construct a ratiometric fluorescence sensor is reasonable and convenient, which
      can be extended to the preparation of other ratiometric fluorescence systems for
      targeted analytes.

PMID- 29336150
TI  - Chemical Exchange Saturation Transfer in Chemical Reactions: A Mechanistic Tool
      for NMR Detection and Characterization of Transient Intermediates.
AB  - The low sensitivity of NMR and transient key intermediates below detection limit
      are the central problems studying reaction mechanisms by NMR. Sensitivity can be
      enhanced by hyperpolarization techniques such as dynamic nuclear polarization or
      the incorporation/interaction of special hyperpolarized molecules. However, all
      of these techniques require special equipment, are restricted to selective
      reactions, or undesirably influence the reaction pathways. Here, we apply the
      chemical exchange saturation transfer (CEST) technique for the first time to NMR
      detect and characterize previously unobserved transient reaction intermediates in
      organocatalysis. The higher sensitivity of CEST and chemical equilibria present
      in the reaction pathway are exploited to access population and kinetics
      information on low populated intermediates. The potential of the method is
      demonstrated on the proline-catalyzed enamine formation for unprecedented in situ
      detection of a DPU stabilized zwitterionic iminium species, the elusive key
      intermediate between enamine and oxazolidinones. The quantitative analysis of
      CEST data at 250 K revealed the population ratio of [Z-iminium]/[exo
      oxazolidinone] 0.02, relative free energy +8.1 kJ/mol (calculated +7.3 kJ/mol),
      and free energy barrier of +45.9 kJ/mol (DeltaG?calc.(268 K) = +42.2 kJ/mol) for
      Z-iminium -> exo-oxazolidinone. The findings underpin the iminium ion
      participation in enamine formation pathway corroborating our earlier theoretical
      prediction and help in better understanding. The reliability of CEST is validated
      using 1D EXSY-build-up techniques at low temperature (213 K). The CEST method
      thus serves as a new tool for mechanistic investigations in organocatalysis to
      access key information, such as chemical shifts, populations, and reaction
      kinetics of intermediates below the standard NMR detection limit.

PMID- 29336152
TI  - Mutation of Phenylalanine-223 to Leucine Enhances Transformation of
      Benzo[a]pyrene by Ring-Hydroxylating Dioxygenase of Sphingobium sp. FB3 by
      increasing Accessibility of the Catalytic Site.
AB  - Burning of agricultural biomass generates polycyclic aromatic hydrocarbons (PAHs)
      including the carcinogen benzo[a]pyrene, of which the catabolism is primarily
      initiated by a ring-hydroxylating dioxygenase (RHD). This study explores
      catalytic site accessibility and its role in preferential catabolism of some PAHs
      over others. The genes flnA1f, flnA2f, flnA3, and flnA4, encoding the oxygenase
      alpha and beta subunits, ferredoxin, and ferredoxin reductase, respectively, of
      the RHD enzyme complex (FlnA) were cloned from Sphingobium sp. FB3 and
      coexpressed in E. coli BL21. The FlnA effectively transformed fluoranthene but
      not benzo[a]pyrene. Substitution of the bulky phenylalanine-223 by leucine
      reduces the steric constraint in the substrate entrance to make the catalytic
      site of FlnA more accessible to large substrates, as visualized by 3D modeling,
      and allows the FlnA mutant to efficiently transform benzo[a]pyrene. Accessibility
      of the catalytic site to PAHs is a mechanism of RHD substrate specificity. The
      results shed light on why some PAHs are more recalcitrant than others.

PMID- 29336151
TI  - Ultrarobust Biochips with Metal-Organic Framework Coating for Point-of-Care
      Diagnosis.
AB  - Most biosensors relying on antibodies as recognition elements fail in harsh
      environment conditions such as elevated temperatures, organic solvents, or
      proteases because of antibody denaturation, and require strict storage conditions
      with defined shelf life, thus limiting their applications in point-of-care and
      resource-limited settings. Here, a metal-organic framework (MOF) encapsulation is
      utilized to preserve the biofunctionality of antibodies conjugated to
      nanotransducers. This study investigates several parameters of MOF coating
      (including growth time, surface morphology, thickness, and precursor
      concentrations) that determine the preservation efficacy against different
      protein denaturing conditions in both dry and wet environments. A plasmonic
      biosensor based on gold nanorods as the nanotransducers is employed as a model
      biodiagnostic platform. The preservation efficacy attained through MOF
      encapsulation is compared to two other commonly employed materials (sucrose and
      silk fibroin). The results show that MOF coating outperforms sucrose and silk
      fibroin coatings under several harsh conditions including high temperature (80 
      degrees C), dimethylformamide, and protease solution, owing to complete
      encapsulation, stability in wet environment and ease of removal at point-of-use
      by the MOF. We believe this study will broaden the applicability of this
      universal approach for preserving different types of on-chip biodiagnostic
      reagents and biosensors/bioassays, thus extending the benefits of advanced
      diagnostic technologies in resource-limited settings.

PMID- 29336153
TI  - Genetic Algorithm Based Design and Experimental Characterization of a Highly
      Thermostable Metalloprotein.
AB  - The development of thermostable and solvent-tolerant metalloproteins is a long
      sought goal for many applications in synthetic biology and biotechnology. In this
      work, we were able to engineer a highly thermostable and organic solvent-stable
      metallo variant of the B1 domain of protein G (GB1) with a tetrahedral zinc
      binding site reminiscent of the one of thermolysin. Promising candidates were
      designed computationally by applying a protocol based on classical and first
      principles molecular dynamics simulations in combination with genetic algorithm
      optimization. The most promising of the computationally predicted mutants was
      expressed and structurally characterized and yielded a highly thermostable
      protein. The experimental results thus confirm the predictive power of the
      applied computational protein engineering approach for the de novo design of
      highly stable metalloproteins.

PMID- 29336154
TI  - Methods for Determining Cell Wall-Bound Phenolics in Maize Stem Tissues.
AB  - We compared two methods with different sample pretreatment, hydrolysis, and
      separation procedures to extract cell wall-bound phenolics. The samples were pith
      and rind tissues from six maize inbred lines reportedly containing different
      levels of cell wall-bound phenolics. In method 1, pretreated samples were
      extracted with a C18 solid-phase extraction cartridge, and it took 6 days to
      complete. In method 2, phenolics were extracted from crude samples with ethyl
      acetate, it took 2 days to complete, and the cost per sample was reduced more
      than 60%. Both methods extracted more 4-coumarate than ferulate. Overall, method
      1 yielded more 4-coumarate, while method 2 yielded more ferulate. The lack of a
      genotype * method interaction and significant correlations between the results
      obtained using the two methods indicate that both methods are reliable for use in
      large-scale plant breeding programs. Method 2, scaled, is proposed for general
      plant biology research.

PMID- 29336155
TI  - Highly Bendable Flexible Perovskite Solar Cells on a Nanoscale Surface Oxide
      Layer of Titanium Metal Plates.
AB  - We report highly bendable and efficient perovskite solar cells (PSCs) that use
      thermally oxidized layer of Ti metal plate as an electron transport layer (ETL).
      The power conversion efficiency (PCE) of flexible PSCs reaches 14.9% with a short
      circuit current density (Jsc) of 17.9 mA/cm2, open-circuit voltage (Voc) of 1.09,
      and fill factor (ff) of 0.74. Moreover, the Ti metal-based PSCs exhibit a
      superior fatigue resistance over indium tin oxide/poly(ethylene terephthalate)
      substrate. Flexible PSCs maintain 100% of their initial PCE even after PSCs are
      bent 1000 times at a bending radius of 4 mm. This excellent performance of
      flexible PSCs is due to high crystalline quality and low oxygen vacancy
      concentration of TiO2 layer. The concentration of oxygen vacancies in the
      oxidized Ti metal surface controls the electric function of TiO2 as ETL of PSCs.
      A decrease in the oxygen vacancy concentration of the TiO2 layer is critical to
      improving the electron collection efficiency of the ETL. Our results suggest that
      Ti metal-based PSCs possess excellent mechanical properties, which can be applied
      to the renewable energy source for flexible electronics.

PMID- 29336156
TI  - Infrared Dielectric Screening Determines the Low Exciton Binding Energy of Metal
      Halide Perovskites.
AB  - The performance of lead-halide perovskites in optoelectronic devices is due to a
      unique combination of factors, including highly efficient generation, transport,
      and collection of photogenerated charge carriers. The mechanism behind efficient
      charge generation in lead-halide perovskites is still largely unknown. Here, we
      investigate the factors that influence the exciton binding energy (Eb) in a
      series of metal-halide perovskites using accurate first-principles calculations
      based on solution of the Bethe-Salpeter equation, coupled to ab initio molecular
      dynamics simulations. We find that Eb is strongly modulated by screening from low
      energy phonons, which account for a factor ~2 Eb reduction, while dynamic
      disorder and rotational motion of the organic cations play a minor role. We
      calculate Eb = 15 meV for MAPbI3, in excellent agreement with recent experimental
      estimates. We then explore how different material combinations (e.g., replacing
      Pb -> Pb:Sn-> Sn; and MA -> FA -> Cs) may lead to different Eb values and
      highlight the mechanisms underlying Eb tuning.

PMID- 29336157
TI  - Glycerol Hydrogen-Bonding Network Dominates Structure and Collective Dynamics in
      a Deep Eutectic Solvent.
AB  - The deep eutectic solvent glyceline formed by choline chloride and glycerol in
      1:2 molar ratio is much less viscous compared to glycerol, which facilitates its
      use in many applications where high viscosity is undesirable. Despite the large
      difference in viscosity, we have found that the structural network of glyceline
      is completely defined by its glycerol constituent, which exhibits complex
      microscopic dynamic behavior, as expected from a highly correlated hydrogen
      bonding network. Choline ions occupy interstitial voids in the glycerol network
      and show little structural or dynamic correlations with glycerol molecules.
      Despite the known higher long-range diffusivity of the smaller glycerol species
      in glyceline, in applications where localized dynamics is essential (e.g., in
      microporous media), the local transport and dynamic properties must be dominated
      by the relatively loosely bound choline ions.

PMID- 29336159
TI  - Ligand-Controlled Copper(I)-Catalyzed Cross-Coupling of Secondary and Primary
      Alcohols to alpha-Alkylated Ketones, Pyridines, and Quinolines.
AB  - One hexanuclear Cu(I) cluster of 4,6-dimethylpyrimidine-2-thiolate efficiently
      catalyzes the dehydrogenative cross-coupling of secondary and primary alcohols to
      alpha-alkylated ketones with high selectivity. This transformation proceeds
      through a one-pot sequence of dehydrogenation of alcohols, condensation of
      aldehydes and ketones, hydrogenation of the resulting alpha,beta-unsaturated
      ketones, and dehydrogenation of the alpha-alkylated alcohols to generate alpha
      alkylated ketones. This catalytic system also displays high activity for the
      annulation reaction of secondary alcohols with gamma-amino- and 2-aminobenzyl
      alcohols to yield pyridines and quinolines, respectively.

PMID- 29336158
TI  - Chromosome Gene Orientation Inversion Networks (GOINs) of Plasmodium Proteome.
AB  - The spatial distribution of genes in chromosomes seems not to be random. For
      instance, only 10% of genes are transcribed from bidirectional promoters in
      humans, and many more are organized into larger clusters. This raises intriguing
      questions previously asked by different authors. We would like to add a few more
      questions in this context, related to gene orientation inversions. Does gene
      orientation (inversion) follow a random pattern? Is it relevant to biological
      activity somehow? We define a new kind of network coined as the gene orientation
      inversion network (GOIN). GOIN's complex network encodes short- and long-range
      patterns of inversion of the orientation of pairs of gene in the chromosome. We
      selected Plasmodium falciparum as a case of study due to the high relevance of
      this parasite to public health (causal agent of malaria). We constructed here for
      the first time all of the GOINs for the genome of this parasite. These networks
      have an average of 383 nodes (genes in one chromosome) and 1314 links (pairs of
      gene with inverse orientation). We calculated node centralities and other
      parameters of these networks. These numerical parameters were used to study
      different properties of gene inversion patterns, for example, distribution, local
      communities, similarity to Erdos-Renyi random networks, randomness, and so on. We
      find clues that seem to indicate that gene orientation inversion does not follow
      a random pattern. We noted that some gene communities in the GOINs tend to group
      genes encoding for RIFIN-related proteins in the proteome of the parasite. RIFIN
      like proteins are a second family of clonally variant proteins expressed on the
      surface of red cells infected with Plasmodium falciparum. Consequently, we used
      these centralities as input of machine learning (ML) models to predict the RIFIN
      like activity of 5365 proteins in the proteome of Plasmodium sp. The best linear
      ML model found discriminates RIFIN-like from other proteins with sensitivity and
      specificity 70-80% in training and external validation series. All of these
      results may point to a possible biological relevance of gene orientation
      inversion not directly dependent on genetic sequence information. This work opens
      the gate to the use of GOINs as a tool for the study of the structure of
      chromosomes and the study of protein function in proteome research.

PMID- 29336160
TI  - Visible-Light Photoredox/Nickel Dual Catalysis for the Cross-Coupling of Sulfinic
      Acid Salts with Aryl Iodides.
AB  - An efficient cross-coupling of sodium or lithium sulfinates with aryl iodides,
      using a combination of nickel and photoredox catalysis, is described. The dual
      catalyst system enables a versatile synthesis of aryl sulfones at room
      temperature in good yields and displays a broad functional group compatibility.
      The potential utility of this method in the late-stage diversification of complex
      molecules and in the conversion of organolithium reagents and sulfur dioxide into
      sulfones is demonstrated.

PMID- 29336161
TI  - Stereoselective Synthesis of 1,4,5-Tri-cis-guaiane Sesquiterpene: First Total
      Synthesis of (-)-Dendroside C Aglycon.
AB  - The first total synthesis of (-)-dendroside C aglycon, consisting of a 1,4,5-tri
      cis-guaiane skeleton, from a versatile hydroazulene intermediate has been
      accomplished. The key features of the syntheses include the stereoselective
      preparation of the unusual cis-hydroazulene core via a sequence of a unique
      Dieckmann condensation of the bicyclic lactone system, which was concisely
      prepared by the tandem conjugate addition and intramolecular allylic alkylation
      of a butenolide precursor, and construction of the characteristic tricyclic
      skeleton by a carbene-mediated cyclopropanation.

PMID- 29336162
TI  - Regioselective Synthesis of alpha- and gamma-Amino Quinolinyl Phosphonamides
      Using N-Heterocyclic Phosphines (NHPs).
AB  - A regioselective phosphonylation of quinolines for the synthesis of alpha-amino
      quinolinyl phosphonamides and gamma-amino quinolinyl phosphonamides has been
      developed under mild reaction conditions. An NHP-thiourea enables selective
      synthesis of alpha-amino quinolinyl phosphonamides by a Reissert-type reaction,
      and an NHP-tosylamide affords gamma-amino quinolinyl phosphonamides via a 1,4
      conjugate addition reaction. The corresponding amino quinolinyl phosphonate
      adducts were obtained in moderate to excellent yields (up to 99% yield) and
      regioselectivities (up to 99:1) with good functional group tolerance.

PMID- 29336163
TI  - Construction of Polycyclic Indole Derivatives via Multiple Aryne Reactions with
      Azaheptafulvenes.
AB  - An efficient [8 + 2]/aryl-ene tandem reaction between azaheptafulvenes and arynes
      has been developed, leading to the formation of cyclohepta[b]indoles in a single
      step with good yield. In addition, employment of excess arynes provides a [8 +
      2]/aryl-ene /[6 + 2] tandem reaction to synthesize polycyclic
      oxacyclohepta[b]indoles. This is the first time that azaheptafulvenes have been
      employed in tandem reactions with arynes.

PMID- 29336164
TI  - Management of Takayasu arteritis.

PMID- 29336165
TI  - Development of novel delivery system for nanoencapsulation of catalase:
      formulation, characterization, and in vivo evaluation using oxidative skin injury
      model.
AB  - One of the main challenges for successful pharmaceutical application of Catalase
      (CAT) is maintaining its stability. Physical immobilization of CAT through nano
      encapsulation was proposed to resolve this challenge. CAT encapsulating niosomes
      (e-CAT) were prepared using Brij(r) 30, 52, 76, 92, and 97 in the presence of
      cholesterol (Ch) by thin film hydration method. Niosomes were characterized for
      encapsulation efficiency % (EE), size, poly-dispersity index (PI), and
      morphology. Kinetic parameters, pH optimum, thermal stability, and reusability of
      CAT were determined. The influence of optimized e-CAT dispersion onto thermally
      injured rat skin was evaluated. Results revealed that encapsulation enhanced CAT
      catalytic efficiency (Vmax/Km). Free CAT and e-CAT had pH optimum at 7.0. e-CAT
      exhibited improved thermal stability where it retained 50% residual activity at
      60  degrees C. Free CAT lost its activity after three consecutive operational
      cycles; however, e-CAT retained 60% of its initial activity following 12 cycles.
      After 24 h of topical application on thermal injury, a significant difference in
      lesion size was observed with e-CAT compared with the control group. Based on
      these encouraging results, CAT immobilization demonstrated a promising novel
      delivery system that enhances its operational stability. In addition, nano
      encapsulated CAT can be anticipated to be beneficial in skin oxidative injury.

PMID- 29336166
TI  - Optimizing outcomes in EGFR mutation-positive NSCLC: which tyrosine kinase
      inhibitor and when?
AB  - Despite the efficacy of standard-of-care EGFR tyrosine kinase inhibitors (TKIs),
      erlotinib, gefitinib and afatinib, in EGFR mutation-positive non-small-cell lung
      cancer, resistance develops, most commonly due to the T790M mutation. Osimertinib
      showed clinical activity in the treatment of T790M-positive disease following
      progression on a first-line TKI, and is approved in this setting. Recently,
      osimertinib improved efficacy versus first-generation TKIs (erlotinib and
      gefitinib) in the first-line setting. Multiple factors can influence first-line
      treatment decisions, including subsequent therapy options, presence of brain
      metastases and tolerability, all of which should be considered in the long-term
      treatment plan. Further research into treatment sequencing is also needed, to
      optimize outcomes in EGFR mutation-positive non-small-cell lung cancer.

PMID- 29336167
TI  - Does personal experience of dementia change attitudes? The Bristol and South
      Gloucestershire survey of dementia attitudes.
AB  - Background It is unclear how attitudes towards people with dementia are formed
      and whether, for instance, increased contact with people with dementia, either
      through work or personal experience alters attitudes. This study used a validated
      questionnaire (the Approaches to Dementia Questionnaire) to examine whether
      having experience of dementia (either as a result of work, or by being affected
      by dementia) is associated with differences in attitudes towards dementia.
      Methods A modified version of the Approaches to Dementia Questionnaire was
      completed by 2201 participants, either online or in written form. Participants
      also recorded their age, gender and ethnicity as well as whether they worked with
      people with dementia or had been personally affected by dementia. Results
      Increased contact with people with dementia was associated with increases in both
      total Approaches to Dementia Questionnaire scores and across both sub-scales
      reflecting more positive person-centred attitudes toward dementia. The highest
      levels of increase were found amongst non-white participants. Conclusions This
      study is, we believe, the first attempt to look systematically at whether greater
      contact with people with dementia is associated with changes in attitudes. The
      results strongly support the contention that increased contact with people with
      dementia leads to more person-centred attitudes, and by inference, less
      stigmatising views.

PMID- 29336168
TI  - Dementia in Eastern Mediterranean countries: A systematic review.
AB  - Globally, there is an increase in the older population, whose lives are affected
      by local cultural norms. In Eastern Mediterranean countries, dementia is
      conventionally hidden from view with few dedicated services or recognition for
      diagnosis. The aim of this systematic review is to explore the limited literature
      on dementia and cognitive impairment among older people in Eastern Mediterranean
      countries to present an evaluation of current practices and to consolidate
      knowledge for future planning. Thirty-three studies were identified for inclusion
      in the review, and four themes were apparent. Firstly, prevalence, comorbidity
      and gender: In Eastern Mediterranean countries, many studies identify that the
      prevalence of dementia is high. As is the case elsewhere, many older adults in
      Eastern Mediterranean countries have at least one coexisting long-term condition,
      and some experience low life-satisfaction. Secondly, culture: In Eastern
      Mediterranean countries, the older adult is highly respected, and placement
      outside of the family home is considered an abandonment of family duty. The term
      dementia carries stigma, and it is widely believed that dementia is caused by
      'fate'. Thirdly, recognition and tools: There is a lack of verified assessment
      instruments to assess for dementia. Despite concerns about the cultural
      appropriateness of the Mini-Mental State Exam, particularly for people who have
      low literacy levels, and low literacy being the norm in Eastern Mediterranean
      countries, the Mini-Mental State Examination is the main assessment instrument.
      Translation and transition of non-Arabic assessment instruments and tools with
      psychometric properties presents a challenge for clinicians. Finally, workforce
      issues: health care workers lack knowledge about dementia, as dementia care is a
      relatively recent addition to the nursing and medical syllabi. While there were
      some inconsistencies in the papers published, many of the articles call for
      increasing educational programmes and health and social care policies to promote
      improved and practical gerontological nursing and medicine. Health care
      professionals need education about sociocultural, religious, and language needs
      to deliver improved culturally sensitive care.

PMID- 29336169
TI  - Bone metastasis target redox-responsive micell for the treatment of lung cancer
      bone metastasis and anti-bone resorption.
AB  - In order to inhibit the growth of lung cancer bone metastasis and reduce the bone
      resorption at bone metastasis sites, a bone metastasis target micelle DOX@DBMs
      ALN was prepared. The size and the zeta potential of DOX@DBNs-ALN were about 60
      nm and -15 mV, respectively. DOX@DBMs-ALN exhibited high binding affinity with
      hydroxyapatite and released DOX in redox-responsive manner. DOX@DBMs-ALN was
      effectively up taken by A549 cells and delivered DOX to the nucleus of A549
      cells, which resulted in strong cytotoxicity on A549 cells. The in vivo
      experimental results indicated that DOX@DBMs-ALN specifically delivered DOX to
      bone metastasis site and obviously prolonged the retention time of DOX in bone
      metastasis site. Moreover, DOX@DBMs-ALN not only significantly inhibited the
      growth of bone metastasis tumour but also obviously reduced the bone resorption
      at bone metastasis sites without causing marked systemic toxicity. Thus, DOX@DBMs
      ALN has great potential in the treatment of lung cancer bone metastasis.

PMID- 29336170
TI  - Nanoparticles for treatment of atherosclerosis: challenges of plasmonic
      photothermal therapy in translational studies.

PMID- 29336171
TI  - Phenolic composition, antioxidant and antinociceptive activities of Syringa
      vulgaris L. bark and leaf extracts.
AB  - Metabolite profile, antioxidant and antinociceptive activities of Syringa
      vulgaris bark and leaf methanolic extracts were investigated. By means of HPLC
      DAD-ESI-TOF and HPLC-DAD-ESI-MS/MS, a total of 33 phenolics were identified,
      including 15 secoiridoids, 6 phenylpropanoids, 3 flavonoids, 3 lignans and 6 low
      molecular weight phenols. Validated quantitative analysis show that syringin
      (2.52%) and rutin (1.13%) are the main phenolic compounds in bark and leaf,
      respectively. Notable radical scavenging and antinociceptive activities of the
      bark and leaf extracts were confirmed by in vitro DPPH? and ABTS?+ assays and by
      in vivo hot-plate method in mice, respectively. Our results could lay the
      scientific basic of future clinical perspectives of lilac bark and leaf.

PMID- 29336172
TI  - Correction to: Erci et al., Green synthesis of silver nanoparticles using Thymbra
      spicata L. var. spicata (zahter) aqueous leaf extract and evaluation of their
      morphology-dependent antibacterial and cytotoxic activity.

PMID- 29336173
TI  - Genome analysis and clinical implications of the bacterial communities in early
      biofilm formation on dental implants restored with titanium or zirconia
      abutments.
AB  - This cross-sectional study aimed to identify and quantify up to 42 target species
      colonizing the early biofilm of dental implants restored with titanium or
      zirconia abutments. A total of 720 samples from 20 healthy individuals were
      investigated. Biofilm samples were collected from the peri-implant sulci, inner
      parts of implants, abutment surfaces and prosthetic crowns over a functioning
      period of 30 days. Checkerboard DNA-DNA hybridization was used for microbial
      detection and quantitation. Clinical characteristics (probing depth, bleeding on
      probing, clinical attachment level and marginal bone loss) were also investigated
      during the monitoring period. Genome counts were low at the implant loading time
      point for both the abutment materials, and increased over time. Both the titanium
      and the zirconia groups presented similar microbial counts and diversity over
      time, and the microbiota was very similar to that colonizing the remaining teeth.
      Clinical findings were consistent with a healthy condition with no significant
      difference regarding marginal bone loss between the two materials.

PMID- 29336174
TI  - Modularising outpatient care delivery: A mixed methods case study at a Finnish
      University Hospital.
AB  - BACKGROUND: Modularisation is a potential means to develop health care delivery
      by combining standardisation and customisation. However, little is known about
      the effects of modularisation on hospital care. The objective was to analyse how
      modularisation may change and support health care delivery in specialised
      hospital care. METHODS: A mixed methods case study methodology was applied using
      both qualitative and quantitative data, including interviews, field notes,
      documents, service usage data, bed count and personnel resource data. Data from a
      reference hospital's unit were used to understand the context and development of
      care delivery in general. RESULTS: The following outcome themes were identified
      from the interviews: balance between demand and supply; support in shift from
      inpatient to outpatient care; shorter treatment times and improved management of
      service production. Modularisation supported the shift from inpatient towards
      outpatient care. Changes in resource efficiency measures were both positive and
      negative; the number of patients per personnel decreased, while the number of
      visits per personnel and the bed utilisation rate increased. CONCLUSIONS:
      Modularisation may support health care providers in classifying patients and
      delivering services according to patients' needs. However, as the findings are
      based on a single university hospital case study, more research is needed.

PMID- 29336175
TI  - A new monoterpene from the poisonous mushroom Trogia venenata, which has caused
      Sudden Unexpected Death in Yunnan province, China.
AB  - A new monoterpene, 6,7,8-trihydroxy-2,6-dimethyloctanoic acid (1), and a known
      sesquiterpene, beta-caryophyllene 4R,5R-oxide (2), as well as four known ergosta
      steroids, 5alpha,8alpha-epidioxyergosta-6,22-dien-3beta-y1 linoleate (3), 3-O
      beta-D-glucopyranosyl-22E,24R-5alpha,8alpha-epidioxyergosta-6,22-dien (4),
      5alpha,8alpha-epidioxy-(22E,24R)-ergosta-6,22-dien-3beta-ol (5) and (22E,24R)
      ergosta-7,22-dien-3beta-ol (6), were isolated from the fruiting bodies of the
      mushroom Trogia venenata. The structures of these compounds were identified by
      the analysis of spectral data. All of the compounds were isolated from this
      mushroom for the first time.

PMID- 29336176
TI  - Replenishing the damaged heart with oxygen by nature-inspired photosynthesis.

PMID- 29336177
TI  - In vivo assessment of a nanofibrous silk tube as nerve guide for sciatic nerve
      regeneration.
AB  - A nanofibrous silk nerve conduit has been evaluated for its efficiency based on
      the promotion of peripheral nerve regeneration in rats. The designed tubes with
      or without Schwann cells were implanted into a 10 mm gap in the sciatic nerves of
      the rats. Four months after the surgery, the regenerated nerves were monitored
      and evaluated by macroscopic assessments and histology. The results demonstrated
      that the nanofibrous grafts, especially in the presence of Schwann cells, enabled
      reconstruction of the rat sciatic nerve trunk with a restoration of nerve
      continuity and formation of nerve fibres with myelination. Histological data
      demonstrated the presence of Schwann and glial cells in regenerated nerves. This
      study strongly supports the feasibility of using artificial nerve grafts for
      peripheral nerve regeneration by bridging large defects in a rat model.

PMID- 29336178
TI  - Evaluation of take-home exposure to asbestos from handling asbestos-contaminated
      worker clothing following the abrasive sawing of cement pipe.
AB  - Although industrial uses of asbestos have declined since the 1970s, in recent
      years there has been a renewed interest in para-occupational ("take-home")
      exposure to these fibers. The aim of this study was to quantify the release of
      asbestos fibers, if any, during the shaking out of crocidolite- and chrysotile
      contaminated clothing in a simulated at-home setting. An exposure study was
      conducted in which personal and area air samples were collected during the
      handling (i.e. shake-out) of work clothing (shirt and pants) previously worn by
      an operator who had cut asbestos-containing cement pipe. During eight "loading"
      events, the operator cut a historically representative asbestos-containing cement
      pipe (10% crocidolite and 25% chrysotile) using a powered abrasive saw.
      Subsequently, 30-minute air samples were collected during four "shake-out"
      events, each of which consisted of the handling of two complete sets of
      contaminated work clothes. Samples were analyzed in accordance with NIOSH methods
      7400 and 7402. The mean phase contrast microscopy equivalent (PCME) airborne
      concentrations were 0.52 f/cc (SD = 0.34 f/cc) for total asbestos fibers, 0.36
      f/cc (SD = 0.26 f/cc) for chrysotile and 0.17 f/cc (SD = 0.096 f/cc) for
      crocidolite. Based on likely estimates of the frequency of laundering activities,
      and assuming that the dusty clothing (1) is not blown off in the occupational
      setting using compressed air and (2) is not shaken out before entering the home,
      a family member handling the clothing could potentially have a lifetime
      cumulative exposure to chrysotile and crocidolite of approximately 0.20 f/cc-year
      and 0.096 f/cc-year, respectively.

PMID- 29336180
TI  - Erratum.

PMID- 29336179
TI  - Belimumab and antipneumococcal vaccination in patients with systemic lupus
      erythematosus.
AB  - In systemic lupus erythematosus (SLE), flares can be caused by infections. In
      particular, Streptococcus pneumoniae infection can be severe or even potentially
      lethal in absence of previous immunization or in case of 'aggressive' systemic
      antibiotic therapy. Immunization efficacy, however, can be reduced in such
      patients with the use of the various immunosuppressive therapeutic regimens. In
      particular, the use of novel monoclonal antibodies against B lymphocytes raises
      concerns over the potential interference with antipneumococcal vaccination.
      Previous studies demonstrated that belimumab therapy did not significantly reduce
      the efficacy of antipneumococcal vaccination, when received after the initiation
      of belimumab therapy. The study being evaluated in this article investigated the
      efficacy of vaccination in relationship to initiation of belimumab therapy in SLE
      patients.

PMID- 29336181
TI  - Analytical and between-subject variation of thrombin generation measured by
      calibrated automated thrombography on plasma samples.
AB  - BACKGROUND: The Calibrated Automated Thrombography (CAT) is an in vitro thrombin
      generation (TG) assay that holds promise as a valuable tool within clinical
      diagnostics. However, the technique has a considerable analytical variation, and
      we therefore, investigated the analytical and between-subject variation of CAT
      systematically. Moreover, we assess the application of an internal standard for
      normalization to diminish variation. METHODS: 20 healthy volunteers donated one
      blood sample which was subsequently centrifuged, aliquoted and stored at -80 
      degrees C prior to analysis. The analytical variation was determined on eight
      runs, where plasma from the same seven volunteers was processed in triplicates,
      and for the between-subject variation, TG analysis was performed on plasma from
      all 20 volunteers. The trigger reagents used for the TG assays included both PPP
      reagent containing 5 pM tissue factor (TF) and PPPlow with 1 pM TF. Plasma, drawn
      from a single donor, was applied to all plates as an internal standard for each
      TG analysis, which subsequently was used for normalization. RESULTS: The total
      analytical variation for TG analysis performed with PPPlow reagent is 3-14% and 9
      13% for PPP reagent. This variation can be minimally reduced by using an internal
      standard but mainly for ETP (endogenous thrombin potential). The between-subject
      variation is higher when using PPPlow than PPP and this variation is considerable
      higher than the analytical variation. CONCLUSION: TG has a rather high inherent
      analytical variation but considerable lower than the between-subject variation
      when using PPPlow as reagent.

PMID- 29336182
TI  - The effects of fermented milk containing Lactococcus lactis subsp. cremoris FC on
      defaecation in healthy young Japanese women: a double-blind, placebo-controlled
      study.
AB  - The objective of this double-blind, placebo-controlled study was to elucidate the
      effects of fermented milk containing Lactococcus lactis subsp. cremoris FC (FC)
      on defaecation in healthy young women. We included 31 women (18-31 years old) who
      were randomly selected into two groups. Subjects in the test group consumed
      fermented milk containing FC, while subjects in the placebo group consumed non
      fermented gelled milk. In the test group, defaecation frequency (both in days and
      times per week) and stool volume significantly increased during the consumption
      of fermented milk containing FC compared with before consumption. These effects
      were also observed in subjects with mild constipation. Furthermore, in subjects
      with mild constipation, stool ammonia concentration was significantly lower in
      the test group than that in the placebo group after 4 weeks. These results
      suggest that fermented milk containing FC is beneficial for improving defaecation
      and faecal properties.

PMID- 29336183
TI  - Postradiation Synovial Sarcoma of the Common Bile Duct: A Previously Unreported
      Anatomic Site.
AB  - Synovial sarcoma is a ubiquitous neoplasm predominantly affecting soft tissues of
      young adults of any gender; few cases have been described in the digestive
      system, mostly in the stomach. The (X;18)(p11.2; q11.2) translocation yields
      unique SS18-SSX fusion genes. Synovial sarcoma has been related to radiotherapy,
      but no synovial sarcoma has been associated with the digestive system. This
      article describes the case of a synovial sarcoma arising along the extrahepatic
      biliary tree, 10 years after the application of an abdominal radiotherapy
      schedule due to a retroperitoneal metastatic seminoma in a male who developed
      progressive obstructive jaundice. Ninety percent of the analyzed cells carried
      the SS18 gene with separation of sequences, thus denoting a translocation. There
      are only 8 post-radiotherapy synovial sarcomas that have been reported
      previously, and this is the first report of a radiotherapy-related synovial
      sarcoma arising from the extrahepatic biliary tree, and the second case described
      in this anatomic region.

PMID- 29336184
TI  - Alpha-amylase, alpha-glucosidase and lipase inhibiting activities of polyphenol
      rich extracts from six common bean cultivars of Southern Italy, before and after
      cooking.
AB  - Common beans (Phaseolus vulgaris) are a good source of nutrients and phenolic
      compounds with versatile health benefits. Polyphenol-rich extracts of six
      ecotypes of P. vulgaris were analysed to determine their phenolic profiles and
      assayed in vitro for inhibitory effects on digestive enzymes relevant to
      carbohydrates and lipids metabolism. The extracts inhibited enzyme activities in
      a dose-dependent manner. IC 50 values ranged from 69 +/- 1.9 to 126 +/- 3.2
      MUg/mL and from 107.01 +/- 4.5 to 184.20 +/- 5.7 MUg/mL, before and after
      cooking, for alpha-amylase, from 39.3 +/- 4.4 to 74.13 +/- 6.9 MUg/mL and from 51
      +/- 7.7 to 122.1 +/- 5.2 MUg/mL for alpha-glucosidase and from 63.11 +/- 7.5 to
      103.2 +/- 5.9 MUg/mL and from 92.0 +/- 6.3 to 128.5 +/- 7.4 MUg/mL for lipase.
      Results suggest encouraging their consumption, being natural sources of enzyme
      inhibitors important for type-2 diabetes and obesity prevention/control. Well
      monitored in vivo studies would help to establish their beneficial effects,
      making them worthwhile of further consideration as functional foods.

PMID- 29336185
TI  - An update on first line therapies for metastatic breast cancer.
AB  - INTRODUCTION: In recent years, outcomes of patients with metastatic breast cancer
      (MBC) have improved due to a greater understanding of the mechanisms of
      carcinogenesis in the development of newer molecularly targeted drugs, especially
      those as a front-line therapy. Remarkable improvements have been made in the
      treatment of hormone receptor positive (HR+) and Her2 positive MBC and currently
      targeted treatment strategies represent a valid first line treatment. Areas
      covered: Herein, the authors provide an overview of the first-line
      pharmacotherapies currently available for the treatment of MBC and provide their
      expert perspectives on the area. Expert opinion: Decisions on the first-line
      treatment of MBC should consider the clinical features of the disease, but also
      the biological mechanisms that regulate tumor cell growth. New and effective
      therapeutic agents have recently been introduced in the first-line therapy of
      MBC. However, to optimize the treatment of patients with metastatic disease,
      clinicians need biomarkers of resistance or sensitivity to targeted therapies.
      Efforts must also be made in developing strategies to personalize treatments of
      MBC patients and to identify those patients who might gain the most benefit from
      new treatment interventions, to save costs and limit toxicity.

PMID- 29336186
TI  - Subcutaneous Fat Necrosis of Newborn: Unfamiliar Histomorphology of a Familiar
      Lesion.

PMID- 29336187
TI  - Efficacy and safety of sirukumab in Japanese patients with moderate to severe
      rheumatoid arthritis inadequately controlled by disease modifying anti-rheumatic
      drugs: Subgroup analysis of a phase 3 study.
AB  - OBJECTIVE: To evaluate the efficacy and safety of sirukumab in Japanese patients
      with active rheumatoid arthritis (RA) uncontrolled by disease-modifying
      antirheumatic drugs. METHODS: This subgroup analysis based on a double-blind,
      placebo-controlled, 52-week phase 3 study (SIRROUND-D) assessed American College
      of Rheumatology (ACR) 20 response at week 16 and van der Heijde-modified Sharp
      score (vdH-S) at week 52 (coprimary endpoints). RESULTS: A total of 168
      (Japanese)/1670 patients received sirukumab 50 mg/4 weeks (q4w, n = 58), 100
      mg/every 2 weeks (q2w, n = 54), or placebo (n = 56) subcutaneously. Significantly
      more patients achieved ACR20 response at week 16 with sirukumab (50 mg q4w:
      69.0%; 100mg q2w: 66.7%) vs. placebo (21.4%; p < .001). Median change from
      baseline in total vdH-S score at week 52 was significantly lower with sirukumab
      (50 mg q4w: 0.3, p = .024; 100 mg q2w: 0.0, p = .002) vs. placebo (1.3).
      Sirukumab consistently showed greater improvements in secondary endpoints at
      weeks 24 and 52. Nasopharyngitis, elevated liver enzymes, injection site erythema
      and upper respiratory tract infections were the common treatment-emergent adverse
      events (TEAEs). Incidences of TEAEs and serious AEs were consistent between
      sirukumab groups through week 52. CONCLUSION: Sirukumab showed clinically
      meaningful improvements consistent with significant improvements in the global
      study. No new safety signals were observed.

PMID- 29336188
TI  - Establishment of reference interval for the tumour marker serum CYFRA 21-1 in
      healthy Chinese Han ethnic adults.
AB  - BACKGROUND: Our aim was to establish the reference interval (RI) for serum CYFRA
      21-1 in healthy Chinese Han ethnic adults, since there has been no report about
      it. METHODS: After screening, 9954 healthy Chinese Han adults (age range 18-95
      years) were recruited, including 6639 (66.7%) males and 3315 (33.3%) females.
      Electrochemiluminescence immunoassay was used to measure serum CYFRA21-1. The RI
      was defined by nonparametric 95% percentile interval. RESULTS: The distribution
      for serum CYFRA21-1 level was non-Gaussian. The RI for healthy Chinese Han adults
      calculated by nonparametric method was 0-4.47 ng/ml in this study, higher than
      that recommended by Roche Diagnostics GmbH (<=3.3 ng/ml). The reference values
      were higher in males than females before 50 years of age, although the difference
      was hardly seen after 50 years of age. The reference value increased with age in
      both males and females. Of slight difference, the increase of male reference
      value was obvious at 60-69 and more than 80 years of age, while that of female
      obvious at 50-69 and more than 80 years of age. CONCLUSIONS: We establish the RI
      for serum CYFRA21-1 in healthy Chinese Han population, which is higher than that
      recommended by Roche Diagnostics GmbH. Furthermore, our study suggests that it is
      necessary to establish the age- and sex-specific RIs for serum CYFRA21-1.

PMID- 29336189
TI  - Depression, sexual satisfaction, and other psychological issues in women with
      polycystic ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS) increases the risk of depression, poor quality
      of life, and low sexual satisfaction of women. The aim of the study was to
      evaluate the prevalence of these disorders and to assess the need for
      psychological consultation at the time of PCOS diagnosis. A case-control single
      center study of 250 women who were diagnosed with PCOS voluntarily filled in an
      anonymous, interactive questionnaire. The inquiry form included 27 questions
      covering the woman's characteristics, satisfaction with their outer appearance
      and sexual life, as well as the Beck Depression Inventory (BDI). Based on the
      BDI, 52% (130/250) of studied women presented depressive symptoms. This group had
      significantly higher body mass index (29.5 +/- 8.1 vs. 24.6 +/- 5.8; p<.001) and
      a lower level of self-attractiveness than other studied women (3.3 +/- 2.2 vs.
      5.4 +/- 2.3; p<.001). Forty two percent (106/250) of women viewed themselves as
      unattractive. A correlation between reduced sexual satisfaction and a sense of
      low attractiveness was noted (r = 0.465, p<.001). Sixty four percent (160/250) of
      women believed that psychological consultation should be offered to all PCOS
      women. Treatment of PCOS women should be multidisciplinary and include
      psychological counseling, especially in obese PCOS women with inadequate family
      support and dissatisfied with their sexual life.

PMID- 29336190
TI  - A cost-effectiveness analysis of calcipotriol plus betamethasone dipropionate
      aerosol foam versus gel for the topical treatment of plaque psoriasis.
AB  - BACKGROUND: Calcipotriol 50 ug/g and betamethasone 0.5 mg/g dipropionate (Cal/BD)
      aerosol foam formulation provides greater effectiveness and improved patient
      preference compared with traditional Cal/BD formulations for the topical
      treatment of plaque psoriasis. OBJECTIVE: To determine the cost-effectiveness of
      Cal/BD foam compared with Cal/BD gel from the Australian perspective. METHODS: A
      Markov model was developed to evaluate the cost-effectiveness of topical Cal/BD
      foam and gel for the treatment of people with plaque psoriasis. Treatment
      effectiveness, safety, and utilities were based on a randomized control trial,
      resource use was informed by expert opinion, and unit costs were obtained from
      public sources. Outcomes were reported in terms of 1-year costs, quality-adjusted
      life years, and incremental cost-effectiveness ratios. All costs were reported in
      2017 Australian Dollars. RESULTS: The model showed that patients using Cal/BD
      foam had more QALYs and higher costs over 1 year compared with patients using
      Cal/BD gel, resulting in a cost of $13,609 per QALY gained at 4-weeks. When 4
      weeks of Cal/BD foam was compared with 8 weeks of Cal/BD gel treatment, Cal/BD
      foam was $8 less expensive and resulted in 0.006 more QALYs gained. Sensitivity
      analyses showed that, compared with Cal/BD ointment, Cal/BD foam was associated
      with an incremental cost of $15,091 per QALY gained. CONCLUSION: Cal/BD foam is
      the most cost-effective Cal/BD formulation for the topical treatment of patients
      with plaque psoriasis.

PMID- 29336191
TI  - Teratogenic potential of nanoencapsulated vitamin A evaluated on an alternative
      model organism, the tunicate Ciona intestinalis.
AB  - Nano-encapsulation is a technology used to pack substances in order to enhance
      their stability and bioavailability, but this packing may interact with living
      systems, causing unexpected toxicity. Vitamin A (vit A) is a substance that has
      received attention, because in developed countries, the increasing availability
      of supplements is leading to its excessive intake. This study aims to compare
      teratogenic effects caused by exposure to the traditional formulation of vit A
      versus nano-encapsulated vit A. We used ascidian embryos as an alternative model.
      Ascidians are marine organisms closely related to vertebrates that share with
      them a body plan and developmental programme, including the morphogenetic role of
      retinoic acid (RA). Our data showed that the adverse effects of exposure to the
      same concentration of the two formulations were different, suggesting that the
      nano-encapsulation increased the bioavailability of the molecule, which could be
      better absorbed and metabolised to RA, the effective teratogenic substance.

PMID- 29336192
TI  - How mass spectrometric approaches applied to bacterial identification have
      revolutionized the study of human gut microbiota.
AB  - INTRODUCTION: Describing the human hut gut microbiota is one the most exciting
      challenges of the 21st century. Currently, high-throughput sequencing methods are
      considered as the gold standard for this purpose, however, they suffer from
      several drawbacks, including their inability to detect minority populations. The
      advent of mass-spectrometric (MS) approaches to identify cultured bacteria in
      clinical microbiology enabled the creation of the culturomics approach, which
      aims to establish a comprehensive repertoire of cultured prokaryotes from human
      specimens using extensive culture conditions. Areas covered: This review first
      underlines how mass spectrometric approaches have revolutionized clinical
      microbiology. It then highlights the contribution of MS-based methods to
      culturomics studies, paying particular attention to the extension of the human
      gut microbiota repertoire through the discovery of new bacterial species. Expert
      commentary: MS-based approaches have enabled cultivation methods to be
      resuscitated to study the human gut microbiota and thus to fill in the blanks
      left by high-throughput sequencing methods in terms of culturing minority
      populations. Continued efforts to recover new taxa using culture methods,
      combined with their rapid implementation in genomic databases, would allow for an
      exhaustive analysis of the gut microbiota through the use of a comprehensive
      approach.

PMID- 29336193
TI  - Enhancement of iodinin solubility by encapsulation into cyclodextrin
      nanoparticles.
AB  - Phenazine is known to regroup planar nitrogen-containing heterocyclic compounds.
      It was used here to enhance the bioavailability of the biologically important
      compound iodinin, which is near insoluble in aqueous solutions. Its water
      solubility has led to the development of new formulations using diverse
      amphiphilic alpha-cyclodextrins (CDs). With the per-[6-desoxy-6-(3
      perfluorohexylpropanethio)-2,3-di-O-methyl]-alpha-CD, we succeeded to get iodinin
      loaded nanoformulations with good parameters such as a size of 97.9 nm, 62%
      encapsulation efficiency and efficient control release. The study presents an
      interesting alternative to optimizing the water solubility of iodinin by chemical
      modifications of iodinin.

PMID- 29336194
TI  - A Robust Multiplex Mass Spectrometric Assay for Screening Small-Molecule
      Inhibitors of CD73 with Diverse Inhibition Modalities.
AB  - CD73/Ecto-5'-nucleotidase is a membrane-tethered ecto-enzyme that works in tandem
      with CD39 to convert extracellular adenosine triphosphate (ATP) into adenosine.
      CD73 is highly expressed on various types of cancer cells and on infiltrating
      suppressive immune cells, leading to an elevated concentration of adenosine in
      the tumor microenvironment, which elicits a strong immunosuppressive effect. In
      preclinical studies, targeting CD73 with anti-CD73 antibody results in favorable
      antitumor effects. Despite initial studies using antibodies, inhibition of CD73
      catalytic activity using small-molecule inhibitors may be more effective in
      lowering extracellular adenosine due to better tumor penetration and
      distribution. To screen small-molecule libraries, we explored multiple
      approaches, including colorimetric and fluorescent biochemical assays, and due to
      some limitations with these assays, we developed a mass spectrometry (MS)-based
      assay. Only the MS-based assay offers the sensitivity and dynamic range required
      for screening small-molecule libraries at a substrate concentration close to the
      Km value of substrate and for evaluating the mode of binding of screening hits.
      To achieve a throughput suitable for high-throughput screening (HTS), we
      developed a RapidFire-tandem mass spectrometry (RF-MS/MS)-based multiplex assay.
      This assay allowed a large diverse compound library to be screened at a speed of
      1536 reactions per 40-50 min.

PMID- 29336195
TI  - Is aspiration and sclerotherapy treatment for hydroceles in the aging male an
      evidence-based treatment?
AB  - Symptomatic hydroceles are commonly treated with surgical repair. They are
      associated with sexual dysfunction in the aging male. Patients who are not fit
      for surgery often undergo aspiration and sclerotherapy of the hydrocele. There is
      a range of sclerosing agents used in the literature. I performed a literature
      search to assess whether one sclerosant was better than the others. STDS is the
      sclerosing agent with the best cure rate after a single injection and low side
      effect rates. The cure rates of sodium tetradecyl sulphate (STDS) after a single
      aspiration and injection were 76%. After multiple treatments 94% achieved a cure.
      Patient satisfaction rates at mean 40 months were 95%. Complication rates were
      generally low and much lower than surgical repair. Aspiration and sclerotherapy
      have a role in treating symptomatic hydroceles. This literature review shows that
      this is over and above its current use in the UK, where it is used for patients
      unfit for general anaesthetic. If the patients are carefully selected for this
      procedure, they can have a good outcome and avoid the higher complication rate
      and longer recovery rates of surgical repair. Patients should be counselled about
      aspiration and sclerotherapy as part of the informed consent process.

PMID- 29336196
TI  - Effect of Chromoendoscopy Filters on Visualization of KTP Laser-Associated Tissue
      Changes: A Cadaveric Animal Model.
AB  - Standard KTP laser (potassium titanyl phosphate) wavelength-specific protective
      eyewear often impairs visualization of tissue changes during laser treatment.
      This sometimes necessitates eyewear removal to evaluate tissue effects, which
      wastes time and poses safety concerns. The objective was to determine if
      "virtual" or "electronic" chromoendoscopy filters, as found on some endoscopy
      platforms, could alleviate the restricted visualization inherent to protective
      eyewear. A KTP laser was applied to porcine laryngeal tissue and recorded via
      video laryngoscopy with 1 optical (Olympus Narrow Band Imaging) and 8 digital
      (Pentax Medical I-scan) chromoendoscopy filters. Videos were viewed by 11
      otolaryngologists wearing protective eyewear. Using a discrete visual analog
      scale, they rated each filter on its ability to improve visualization,. No filter
      impaired visualization; 5 of 9 improved visualization. Based on statistical
      significance, the number of positive responses, and the lack of negative
      responses, narrow band imaging and the I-scan tone enhancement filter for
      leukoplakia performed best. These filters could shorten procedure time and
      improve safety; therefore, further clinical evaluation is warranted.

PMID- 29336198
TI  - Long non-coding RNA GPR65-1 is up-regulated in gastric cancer and promotes tumor
      growth through the PTEN-AKT-slug signaling pathway.
AB  - Increasing evidence has shown that abnormal expression of lncRNAs is involved in
      various biological behaviors and major cellular pathways of human cancers.
      However, the role of lncRNAs in the progression of gastric cancer has not been
      adequately investigated. Therefore, in this study, we investigated the expression
      levels of linc-GPR65-1 using Quantitative real-time PCR (qRT-PCR) and found that
      linc-GPR65-1 was significantly up-regulated in 50 gastric cancer tissues compared
      to the corresponding normal tissues. In addition, increased linc-GPR65-1
      expression was associated with TNM stage (P = 0.037), tumor size (P = 0.024),
      distal metastasis (P = 0.023), and poor prognosis of gastric cancer patients.
      Moreover, functional assays indicated that decreased linc-GPR65-1 expression
      inhibited the aggressive phenotypes of gastric cancer cells, and enhanced linc
      GPR65-1 expression resulted in the opposite phenomenon. Then, a cancer signaling
      phosphoantibody microarray was conducted to explore the potential mechanisms of
      linc-GPR65-1 in regulating gastric cancer progression and observed that linc
      GPR65-1 could regulate the PTEN-AKT-slug signaling pathway. These data showed
      that linc-GPR65-1, regulating the PTEN-AKT-slug signaling pathway, might act as a
      tumor promoter and serve as a novel target for gastric cancer prevention and
      therapy.

PMID- 29336197
TI  - Neurosensory Deficits Vary as a Function of Point of Care in Pediatric Mild
      Traumatic Brain Injury.
AB  - Neurosensory abnormalities are frequently observed following pediatric mild
      traumatic brain injury (pmTBI) and may underlie the expression of several common
      concussion symptoms and delay recovery. Importantly, active evaluation of
      neurosensory functioning more closely approximates real-world (e.g., physical and
      academic) environments that provoke symptom worsening. The current study
      determined whether symptom provocation (i.e., during neurosensory examination)
      improved classification accuracy relative to pre-examination symptom levels and
      whether symptoms varied as a function of point of care. Eighty-one pmTBI were
      recruited from the pediatric emergency department (PED; n = 40) or outpatient
      concussion clinic (n = 41), along with matched (age, sex, and education) healthy
      controls (HC; n = 40). All participants completed a brief (~ 12 min) standardized
      neurosensory examination and clinical questionnaires. The magnitude of symptom
      provocation upon neurosensory examination was significantly higher for concussion
      clinic than for PED patients. Symptom provocation significantly improved
      diagnostic classification accuracy relative to pre-examination symptom levels,
      although the magnitude of improvement was modest, and was greater in the
      concussion clinic. In contrast, PED patients exhibited worse performance on
      measures of balance, vision, and oculomotor functioning than the concussion
      clinic patients, with no differences observed between both samples and HC.
      Despite modest sample sizes, current findings suggest that point of care
      represents a critical but highly under-studied variable that may influence
      outcomes following pmTBI. Studies that rely on recruitment from a single point of
      care may not generalize to the entire pmTBI population in terms of how
      neurosensory deficits affect recovery.

PMID- 29336199
TI  - The Rust Fungus Melampsora larici-populina Expresses a Conserved Genetic Program
      and Distinct Sets of Secreted Protein Genes During Infection of Its Two Host
      Plants, Larch and Poplar.
AB  - Mechanisms required for broad-spectrum or specific host colonization of plant
      parasites are poorly understood. As a perfect illustration, heteroecious rust
      fungi require two alternate host plants to complete their life cycles. Melampsora
      larici-populina infects two taxonomically unrelated plants, larch, on which
      sexual reproduction is achieved, and poplar, on which clonal multiplication
      occurs, leading to severe epidemics in plantations. We applied deep RNA
      sequencing to three key developmental stages of M. larici-populina infection on
      larch: basidia, pycnia, and aecia, and we performed comparative transcriptomics
      of infection on poplar and larch hosts, using available expression data. Secreted
      protein was the only significantly overrepresented category among differentially
      expressed M. larici-populina genes between the basidial, the pycnial, and the
      aecial stages, highlighting their probable involvement in the infection process.
      Comparison of fungal transcriptomes in larch and poplar revealed a majority of
      rust genes were commonly expressed on the two hosts and a fraction exhibited host
      specific expression. More particularly, gene families encoding small secreted
      proteins presented striking expression profiles that highlight probable candidate
      effectors specialized on each host. Our results bring valuable new information
      about the biological cycle of rust fungi and identify genes that may contribute
      to host specificity.

PMID- 29336200
TI  - Does CPAP Affect Patient-Reported Voice Outcomes?
AB  - Upper aerodigestive tract symptoms are common in patients with obstructive sleep
      apnea (OSA). It remains unclear whether continuous positive airway pressure
      (CPAP) improves or worsens these otolaryngology symptoms. As therapy-related side
      effects limit CPAP adherence, this study aimed to determine if CPAP negatively
      affects voice, sinonasal, and reflux symptoms of the upper airway. Case series
      with planned data collection was performed at an academic otolaryngology sleep
      center. Newly diagnosed patients with OSA were evaluated before and 6 months
      after initiating CPAP therapy. Data collected included CPAP data download, Reflux
      Symptom Index (RSI), Epworth Sleepiness Scale (ESS), Voice Handicap Index 10 (VHI
      10), Sino-Nasal Questionnaire (SNQ), and oral dryness visual analog scale (VAS).
      For the 11 CPAP-adherent participants, the RSI significantly improved with CPAP
      (mean RSI, 22.0-9.5; P = .002); however, the VAS, VHI-10, and SNQ did not change
      after 6 months of CPAP therapy. In a small sample size, patient-reported voice
      outcomes (VHI-10) and other upper aerodigestive tract symptoms did not worsen
      with CPAP; rather, CPAP therapy was associated with a reduction in reflux
      symptoms.

PMID- 29336201
TI  - Poor Motor-Function Recovery after Spinal Cord Injury in Anxiety-Model Mice with
      Phospholipase C-Related Catalytically Inactive Protein Type 1 Knockout.
AB  - Mice with a knockout of phospholipase C (PLC)-related inactive protein type 1
      (PRIP1-/- mice) display anxiety-like behavior and altered gamma-aminobutyric acid
      (GABA)A-receptor pharmacology. Here, we examined associations between anxiety and
      motor-function recovery in PRIP1-/- mice after a spinal cord injury (SCI) induced
      by a moderate contusion injury at the 10th thoracic level. Uninjured PRIP1-/-
      mice showed less distance than wild-type (WT) mice in the center 25% in an open
      field test (OFT), indicating anxiety-like behavior. Anxiety behavior increased in
      both WT and PRIP1-/- mice after SCI. WT and PRIP1-/- mice were completely
      paralyzed on day 1 after SCI, but gradually recovered until reaching a plateau at
      ~4 weeks. After SCI, the PRIP1-/- mice had significantly greater motor
      dysfunction than the WT mice. In WT mice after SCI, the percentage of distance
      spent in the center 25% of the OFT was correlated with the OFT distance traveled
      and velocity, and with the reaction time in a plantar pressure-sensitivity
      mechanical test. In PRIP1-/- mice after SCI, the percentage of distance spent in
      the center 25% of the OFT was correlated with the OFT distance traveled and with
      the latency to fall in the rotarod test. Six weeks after SCI, ionized calcium
      binding adaptor molecule 1 (Iba1) and glial fibrillary acidic protein (GFAP)
      expressions were elevated at the lesion epicenter in PRIP1-/- mice, and spinal
      cord atrophy and demyelination were more severe than in WT mice. The axonal fiber
      development was also decreased in PRIP1-/- mice, consistent with the poor motor
      function recovery after SCI in these mice.

PMID- 29336202
TI  - The Prediction Value of the Systemic Inflammation Score for Oral Cavity Squamous
      Cell Carcinoma.
AB  - Objectives This study aimed to investigate the potential prognostic role of the
      oral cancer systemic inflammation score (SIS) based on serum albumin levels and
      the lymphocyte-to-monocyte ratio in patients with oral squamous cell carcinoma
      (OSCC) after treatment. Study Design A retrospective cohort study. Setting
      Tertiary care center. Subjects and Methods The study involved 613 patients who
      were treated for OSCC between September 2005 and December 2014. The association
      of the oral cancer SIS with various clinicopathological features was
      investigated. A nomogram based on different clinicopathological features and SIS
      was established to predict prognosis. Results Higher SIS was significantly
      associated with older age ( P = .0013), advanced tumor status ( P < .0001), tumor
      depth ( P < .0001), advanced overall pathologic stage ( P < .0001), and
      extranodal extension ( P = .0045), as well as the presence of perineural invasion
      ( P = .0341). Higher SIS, older age, overall stage, and extranodal extension were
      demonstrated to be independent prognostic indicators for shorter overall survival
      ( P < .0001). A nomogram comprising SIS, TNM stage, and the degree of cell
      differentiation, as well as perineural invasion and extranodal extension, was
      developed to predict the prognosis of these patients. The c-index of the nomogram
      model based on TNM staging only was 0.688 and could be increased to 0.752 if SIS
      and several other clinicopathological parameters were incorporated. Conclusions
      Higher SIS is associated with many poor prognosticators, and the nomogram that
      was established and based on the incorporation of SIS might strengthen the
      prediction of prognosis in patients with OSCC.

PMID- 29336203
TI  - Aberrant interactions of peripheral measures and neurometabolites with lipids in
      complex regional pain syndrome using magnetic resonance spectroscopy: A pilot
      study.
AB  - Background The aim of this study was to assess peripheral measures and central
      metabolites associated with lipids using magnetic resonance spectroscopy. Results
      Twelve patients with complex regional pain syndrome (CRPS) and 11 healthy
      controls participated. Using magnetic resonance spectroscopy, we measured the
      levels of lipid 13a (Lip13a) and lipid 09 (Lip09) relative to total creatine
      (tCr) levels in the right and left thalamus. We found negative correlations of
      Lip13a/tCr in the right thalamus with red blood cells or neutrophils, but a
      positive correlation between Lip13a/tCr and lymphocytes in the controls. We found
      negative correlations between Lip09/tCr and peripheral pH or platelets in the
      controls. There were positive correlations between Lip09a/tCr and myo
      inositol/tCr, between Lip13a/tCr and N-acetylaspartate (NAA)/tCr, and between
      Lip09/tCr and NAA/tCr in healthy controls. On the other hand, there were positive
      correlations between Lip13a/tCr and Lip09/tCr and urine pH in CRPS patients.
      There were significant correlations between Lip13a/tCr or Lip09/tCr and different
      peripheral measures depending on the side of the thalamus (right or left) in CRPS
      patients. Conclusion This is the first report indicating that abnormal
      interactions of Lip13a and Lip09 in the thalamus with peripheral measures and
      central metabolites may mediate the complex pathophysiological mechanisms
      underlying CRPS.

PMID- 29336205
TI  - Prediction of natalizumab anti-drug antibodies persistency.
AB  - BACKGROUND: Anti-drug antibodies (ADA) against natalizumab develop early during
      treatment. ADA persistency is defined by two consecutive positive results as
      performed by the current qualitative ELISA assay (positive/negative). Very little
      is known about the magnitude of the natalizumab ADA response and persistency.
      DESIGN/METHODS: We developed a highly sensitive natalizumab ADA titration assay
      on the Meso Scale Discovery (MSD) platform and a pharmacokinetic (PK) assay. We
      included 43 patients with a positive ELISA-ADA result within 6 months of
      treatment initiation (baseline) of whom a follow-up serum sample was available 12
      30 months after treatment start. MSD-ADA titres and drug levels were measured.
      RESULTS: Median MSD-ADA titre at baseline was 4881 and 303 at follow-up. A titre
      of >400 at baseline had a 94% sensitivity and 89% specificity to predict ADA
      persistency. Reversion to ADA negativity occurred in 10 patients with mean drug
      levels of 10.8 MUg/mL. The median trough drug level in ADA-positive samples was 0
      ug/mL. PK levels and ADA titres correlated strongly negatively ( r = -0.67).
      CONCLUSION: High baseline natalizumab ADA titres accurately predict persistency.
      Despite continuous treatment, the majority of patients with persistent ADA had no
      detectable drug levels indicating loss of efficacy in line with phase 3 study
      results.

PMID- 29336206
TI  - Working in global health: A planning and implementation framework for
      international electives.
AB  - PURPOSE: Propose a framework for planning and undertaking an international
      elective. METHODS: On returning from conducting maternal health and well-being
      research in several remote communities in India, two undergraduate medical
      students have reflected on and documented their experiences with the view to
      assisting other students (and their supervisors) considering undertaking an
      international elective. RESULTS: A framework for undertaking clinical or research
      electives in remote or rural communities is presented. The framework comprises
      three distinct phases: Pre-departure planning and briefing, in-country
      experiences and returning from the elective and considers a range of factors to
      ensure that, as a minimum, visiting students "do no harm" and are themselves not
      harmed. CONCLUSIONS: Students' home institutions have a duty of care for
      preparing them for their international electives by providing pre-departure
      training, support during the elective and comprehensive de-briefing on their
      return. These electives should be evaluated (including by host communities) to
      ensure that exchanges are socially accountable, with no harm to the often
      vulnerable communities in which students gain considerable experience. Also
      important is that future students build on the positive experiences of their
      predecessors to ensure sustainability of any interventions in host communities.

PMID- 29336204
TI  - Continuous Infusion of Phenelzine, Cyclosporine A, or Their Combination:
      Evaluation of Mitochondrial Bioenergetics, Oxidative Damage, and Cytoskeletal
      Degradation following Severe Controlled Cortical Impact Traumatic Brain Injury in
      Rats.
AB  - To date, all monotherapy clinical traumatic brain injury (TBI) trials have
      failed, and there are currently no Food and Drug Administration (FDA)-approved
      pharmacotherapies for the acute treatment of severe TBI. Due to the complex
      secondary injury cascade following injury, there is a need to develop multi
      mechanistic combinational neuroprotective approaches for the treatment of acute
      TBI. As central mediators of the TBI secondary injury cascade, both mitochondria
      and lipid peroxidation-derived aldehydes make promising therapeutic targets.
      Cyclosporine A (CsA), an FDA-approved immunosuppressant capable of inhibiting the
      mitochondrial permeability transition pore, and phenelzine (PZ), an FDA-approved
      monoamine oxidase inhibitor capable of scavenging neurotoxic lipid peroxidation
      derived aldehydes, have both been shown to be partially neuroprotective following
      experimental TBI. Therefore, it follows that the combination of PZ and CsA may
      enhance neuroprotection over either agent alone through the combining of distinct
      but complementary mechanisms of action. Additionally, as the first 72 h
      represents a critical time period following injury, it follows that continuous
      drug infusion over the first 72 h following injury may also lead to optimal
      neuroprotective effects. This is the first study to examine the effects of a 72 h
      subcutaneous continuous infusion of PZ, CsA, and the combination of these two
      agents on mitochondrial respiration, mitochondrial bound 4-hydroxynonenal (4
      HNE), and acrolein, and alpha-spectrin degradation 72 h following a severe
      controlled cortical impact injury in rats. Our results indicate that
      individually, both CsA and PZ are able to attenuate mitochondrial 4-HNE and
      acrolein, PZ is able to maintain mitochondrial respiratory control ratio and
      cytoskeletal integrity but together, PZ and CsA are unable to maintain
      neuroprotective effects.

PMID- 29336207
TI  - Cytotoxicity of Ciprofloxacin and Steroids in Mouse Tympanic Membrane
      Fibroblasts.
AB  - Objective Ciprofloxacin, commonly given as eardrops, has been shown to adversely
      affect tympanic membrane fibroblasts. Dexamethasone potentiates this effect. A
      newly available eardrop contains ciprofloxacin and fluocinolone, a more potent
      steroid. We evaluated the cytotoxic effects of this preparation on mouse tympanic
      membrane fibroblasts. Study Design Prospective, in vitro. Setting Academic
      laboratory. Subjects and Methods In experiment 1, fibroblasts were exposed to
      1:10 dilutions of commercially available 0.3% ofloxacin, 0.3% ciprofloxacin, 0.3%
      ciprofloxacin + 0.1% dexamethasone, 0.3% ciprofloxacin + 0.025% fluocinolone, or
      dilute hydrochloric acid (control), twice within 24 hours. In experiment 2, cells
      were also treated with the dilutions of the pure form of dexamethasone 0.1% or
      fluocinolone 0.025%, alone and in combination with ofloxacin or ciprofloxacin.
      Cells were exposed to the solutions for 2 hours each time and were placed back in
      growth media after the treatments. Cells were observed with phase-contrast
      microscope until the cytotoxicity assay was performed. Results Survival of
      fibroblasts treated with ofloxacin was not different from the control.
      Fibroblasts treated with ciprofloxacin, ciprofloxacin + dexamethasone, or
      ciprofloxacin + fluocinolone had much lower survival (all P < .0001). Cells
      treated with ciprofloxacin + fluocinolone had lower survival than ciprofloxacin (
      P < .0001) and ciprofloxacin + dexamethasone ( P = .0001). Steroids alone also
      decreased fibroblast survival compared to control ( P < .0001). The combination
      of dexamethasone or fluocinolone with ciprofloxacin, but not ofloxacin, further
      decreased fibroblast survival ( P < .0001). Phase-contrast images mirrored the
      cytotoxicity findings. Conclusion Tympanic membrane fibroblast cytotoxicity of
      ciprofloxacin is potentiated by corticosteroids. This effect may be deleterious
      when treating a healing perforation but beneficial when treating granulation
      tissue on the tympanic membrane.

PMID- 29336208
TI  - The Effects of Sex Differences and Hormonal Contraception on Outcomes after
      Collegiate Sports-Related Concussion.
AB  - There is conflicting evidence regarding whether females are more adversely
      affected after concussion than males. Further, recent research suggests that
      hormonal contraceptive (HC) use may affect symptom severity and duration post
      concussion. The objective of this study was to examine the effects of sex and HC
      use on outcomes following concussion among collegiate varsity athletes. We
      hypothesized that females would have longer length of recovery (LOR), and that
      peak symptom severity would be associated with longer LOR in both males and
      females. Among females, we hypothesized that non-HC users would have longer LOR
      and higher peak symptom severity than HC users. Ninety collegiate student
      athletes were included in this study (40 males, 50 females; 24 HC users, 25 non
      HC users). Demographic, injury, and recovery information was abstracted via
      retrospective record review. LOR was defined as days between injury and clearance
      for full return to play by team physician. Peak symptom severity score (Sport
      Concussion Assessment Tool [SCAT] 2 or 3) was used in analyses. Study results
      revealed that males had shorter LOR than females (F[1, 86] = 5.021, p < 0.05, d =
      0.49), but had comparable symptom severity scores. Symptom severity was strongly
      related to LOR for males (r = 0.513, p < 0.01) but not females (r = -0.003, p >
      0.05). Among females, non-HC users demonstrated higher symptom severity than HC
      users (F[1,47] = 5.142, p < 0.05, d = 0.70). No significant differences between
      female HC users and non-HC users on LOR were observed. This study provides
      evidence for differential concussion outcomes between male and female collegiate
      athletes and between HC users and nonusers among females.

PMID- 29336209
TI  - Effects of Treadmill Training Combined with Serotonergic Interventions on
      Spasticity after Contusive Spinal Cord Injury.
AB  - Spasticity usually emerges during the course of recovery from spinal cord injury
      (SCI). While medications and physical rehabilitation are prescribed to alleviate
      spastic symptoms, the insufficiency of their effects remains an important problem
      to be addressed. Given the challenges associated with increasing the dose of
      medication, we hypothesized that a combination therapy with medication and
      physical rehabilitation can be effective. Therefore, we examined the effects of
      treadmill training (TMT) along with serotonergic medication using a spastic rat
      model after contusive injury. Spasticity-strong SCI rats were selected 4 weeks
      after SCI and received one of the following interventions for 2 weeks: only TMT,
      TMT with fluoxetine (a selective serotonin re-uptake inhibitor), TMT with
      cyproheptadine (a 5-HT2 receptor antagonist), only fluoxetine, or only
      cyproheptadine. We performed the swimming test to quantify the frequency of
      spastic behaviors. We also evaluated hindlimb locomotor functions every week. At
      the end of the intervention, we examined the Hoffman reflex from the plantar
      muscle and the immunoreactivity of the 5-HT2A receptor in spinal cord tissues.
      While the TMT group and cyproheptadine-treated groups showed decreased spastic
      behaviors and reduction in spinal hyperreflexia, the fluoxetine-treated group
      showed the opposite effect, even with TMT. Moreover, TMT suppressed the
      expression of the 5-HT2A receptor in the lumbar spinal motor neurons, while
      cyproheptadine treatment did not change it. We did not observe any differences in
      locomotor functions between the groups. Taken together, our findings indicate
      that TMT and cyproheptadine significantly alleviated spastic symptoms, but did
      not show synergistic or additive effects.

PMID- 29336210
TI  - Semi-supervised identification of cancer subgroups using survival outcomes and
      overlapping grouping information.
AB  - Identification of cancer patient subgroups using high throughput genomic data is
      of critical importance to clinicians and scientists because it can offer
      opportunities for more personalized treatment and overlapping treatments of
      cancers. In spite of tremendous efforts, this problem still remains challenging
      because of low reproducibility and instability of identified cancer subgroups and
      molecular features. In order to address this challenge, we developed Integrative
      Genomics Robust iDentification of cancer subgroups (InGRiD), a statistical
      approach that integrates information from biological pathway databases with high
      throughput genomic data to improve the robustness for identification and
      interpretation of molecularly-defined subgroups of cancer patients. We applied
      InGRiD to the gene expression data of high-grade serous ovarian cancer from The
      Cancer Genome Atlas and the Australian Ovarian Cancer Study. The results indicate
      clear benefits of the pathway-level approaches over the gene-level approaches. In
      addition, using the proposed InGRiD framework, we also investigate and address
      the issue of gene sharing among pathways, which often occurs in practice, to
      further facilitate biological interpretation of key molecular features associated
      with cancer progression. The R package "InGRiD" implementing the proposed
      approach is currently available in our research group GitHub webpage (
      https://dongjunchung.github.io/INGRID/ ).

PMID- 29336211
TI  - The effect of altering loading distance on skeleton start performance: Is higher
      pre-load velocity always beneficial?
AB  - Athletes initiating skeleton runs differ in the number of steps taken before
      loading the sled. We aimed to understand how experimentally modifying loading
      distance influenced sled velocity and overall start performance. Ten athletes
      (five elite, five talent; 67% of all national athletes) underwent two to four
      sessions, consisting of two dry-land push-starts in each of three conditions
      (preferred, long and short loading distances). A magnet encoder on the sled wheel
      provided velocity profiles and the overall performance measure (sled acceleration
      index). Longer pre-load distances (12% average increase from preferred to long
      distances) were related to higher pre-load velocity (r = 0.94), but lower load
      effectiveness (r = -0.75; average reduction 29%). Performance evaluations across
      conditions revealed that elite athletes' preferred distance push-starts were
      typically superior to the other conditions. Short loading distances were
      generally detrimental, whereas pushing the sled further improved some talent
      squad athletes' performance. Thus, an important trade-off between generating high
      pre-load velocity and loading effectively was revealed, which coaches should
      consider when encouraging athletes to load later. This novel intervention study
      conducted within a real-world training setting has demonstrated the scope to
      enhance push-start performance by altering loading distance, particularly in
      developing athletes with less extensive training experience.

PMID- 29336212
TI  - Simulated Microgravity Impairs Cardiac Autonomic Neurogenesis from Neural Crest
      Cells.
AB  - Microgravity-induced alterations in the autonomic nervous system (ANS) contribute
      to derangements in both the mechanical and electrophysiological function of the
      cardiovascular system, leading to severe symptoms in humans following space
      travel. Because the ANS forms embryonically from neural crest (NC) progenitors,
      we hypothesized that microgravity can impair NC-derived cardiac structures.
      Accordingly, we conducted in vitro simulated microgravity experiments employing
      NC genetic lineage tracing in mice with cKitCreERT2/+, Isl1nLacZ, and Wnt1-Cre
      reporter alleles. Inducible fate mapping in adult mouse hearts and pluripotent
      stem cells (iPSCs) demonstrated reduced cKitCreERT2/+-mediated labeling of both
      NC-derived cardiomyocytes and autonomic neurons (P < 0.0005 vs. controls). Whole
      transcriptome analysis, suggested that this effect was associated with repressed
      cardiac NC- and upregulated mesoderm-related gene expression profiles, coupled
      with abnormal bone morphogenetic protein (BMP)/transforming growth factor beta
      (TGF-beta) and Wnt/beta-catenin signaling. To separate the manifestations of
      simulated microgravity on NC versus mesodermal-cardiac derivatives, we conducted
      Isl1nLacZ lineage analyses, which indicated an approximately 3-fold expansion (P
      < 0.05) in mesoderm-derived Isl-1+ pacemaker sinoatrial nodal cells; and an
      approximately 3-fold reduction (P < 0.05) in cardiac NC-derived ANS cells,
      including sympathetic nerves and Isl-1+ cardiac ganglia. Finally, NC-specific
      fate mapping with a Wnt1-Cre reporter iPSC model of murine NC development
      confirmed that simulated microgravity directly impacted the in vitro development
      of cardiac NC progenitors and their contribution to the sympathetic and
      parasympathetic innervation of the iPSC-derived myocardium. Altogether, these
      findings reveal an important role for gravity in the development of NCs and their
      postnatal derivatives, and have important therapeutic implications for human
      space exploration, providing insights into cellular and molecular mechanisms of
      microgravity-induced cardiomyopathies/channelopathies.

PMID- 29336213
TI  - Heart versus head: Differential bodily feedback causally alters economic decision
      making.
AB  - Metaphorically, altruistic acts, such as monetary donations, are said to be
      driven by the heart, whereas sound financial investments are guided by reason,
      embodied by the head. In a unique experiment, we tested the effects of these
      bodily metaphors using biofeedback and an incentivized economic decision-making
      paradigm. Participants played a repeated investment game with a simulated
      partner, alternating between tactical investor and altruistic investee. When
      making decisions, participants received counterbalanced visual feedback from
      their own or a simulated partner's heart or head, as well as no feedback. As
      investor, participants transferred a greater proportion of their endowments when
      exposed to visual feedback from their own head than to feedback from their own
      heart or no feedback at all. These effects were not observed when the source of
      the feedback was the simulated partner. As investee, heart feedback predicted
      greater altruistic returns than head or no feedback, but this effect did not
      differ based on source (own vs partner). Consistent with a dual-process
      framework, we suggest that people may be encouraged to invest more or be more
      altruistic when receiving bodily feedback from conceptually diametric sources.

PMID- 29336214
TI  - Direct red 81 adsorption on iron filings from aqueous solutions; kinetic and
      isotherm studies.
AB  - Direct Red 81 (DR-81) dye with a very high water solubility is widely used in
      many industries particularly textile industries. This study aimed to evaluate the
      practicability of using iron filings for the adsorption of DR-81 dye from the
      aqueous solutions. The effects of pH, adsorbent dose, initial DR-81 dye
      concentration, and adsorption time on adsorption process were also evaluated. The
      maximum of adsorption efficiency of DR-81 dye achieved in the optimum pH: 3,
      adsorbent dose: 2.5 g/L, contact time: 30 min, and initial dye concentration: 50
      mg/L. The dye adsorption efficiency is increased by increasing the adsorbent dose
      and adsorption time. The kinetic and isotherm studies indicated that the
      adsorption process obeys a pseudo-first-order and Langmuir isotherm models. The
      experimental studies indicated that iron filings had the potential to act as an
      alternative adsorbent to remove the DR-81 dye from an aqueous solution.

PMID- 29336215
TI  - Noninvasive Real-Time Assessment of Cell Viability in a Three-Dimensional Tissue.
AB  - Maintaining cell viability within 3D tissue engineering scaffolds is an essential
      step toward a functional tissue or organ. Assessment of cell viability in 3D
      scaffolds is necessary to control and optimize tissue culture process. Monitoring
      systems based on respiration activity of cells (e.g., oxygen consumption) have
      been used in various cell cultures. In this research, an online monitoring system
      based on respiration activity was developed to monitor cell viability within
      acellular lung scaffolds. First, acellular lung scaffolds were recellularized
      with human umbilical cord vein endothelial cells, and then, cell viability was
      monitored during a 5-day period. The real-time monitoring system generated a cell
      growth profile representing invaluable information on cell viability and
      proliferative states during the culture period. The cell growth profile obtained
      by the monitoring system was consistent with 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide analysis and glucose consumption measurement. This
      system provided a means for noninvasive, real-time, and repetitive investigation
      of cell viability. Also, we showed the applicability of this monitoring system by
      introducing shaking as an operating parameter in a long-term culture.

PMID- 29336216
TI  - Sulfamethoxazole removal in membrane-photocatalytic reactor system -
      experimentation and modelling.
AB  - In this study, the efficacy of membrane-photocatalytic reactor (MPR) in
      sulfamethoxazole (SMX) removal was explored at a fixed initial SMX concentration,
      i.e. 100 mg/L. A supported catalyst, i.e. TiO2 on granular activated carbon (GAC
      TiO2), was used for MPR experiments. The SMX removal efficiency of the MPR was
      investigated under a range of hydraulic retention time (i.e. HRT from 51 to 152.5
      min) and TiO2 catalyst dosage (55-50 mg/L). A maximum SMX removal efficiency of
      83.6% was observed under 220 mg/L catalyst dosage and 80 min HRT. The increase in
      catalyst dosage from 55 to 550 mg/L has increased the transmembrane pressure of
      the reactor from 9.8 to 22.2 kPa. A multiple non-linear regression model was
      developed based on the experimental data and its significance was analyzed using
      two-way ANOVA. Based on the model, the optimal HRT and catalyst dosage for
      complete SMX removal (100%) were found out. The comparison of photocatalytic
      degradation experiments with sorption experiments conducted earlier revealed that
      SMX removal in the MPR was mainly by photocatalytic degradation and not by
      adsorption onto GAC-TiO2 catalyst. However, the performance of MPR in removing
      other emerging pollutants from real-time wastewaters could be explored before its
      field-scale application.

PMID- 29336217
TI  - Coronary anomaly: when you think you've seen it all.

PMID- 29336218
TI  - The different audiences of science communication: A segmentation analysis of the
      Swiss population's perceptions of science and their information and media use
      patterns.
AB  - Few studies have assessed whether populations can be divided into segments with
      different perceptions of science. We provide such an analysis and assess whether
      these segments exhibit specific patterns of media and information use. Based on
      representative survey data from Switzerland, we use latent class analysis to
      reconstruct four segments: the "Sciencephiles," with strong interest for science,
      extensive knowledge, and a pronounced belief in its potential, who use a variety
      of sources intensively; the "Critically Interested," also with strong interest
      and support for science but with less trust in it, who use similar sources but
      are more cautious toward them; the "Passive Supporters" with moderate levels of
      interest, trust, and knowledge and tempered perceptions of science, who use fewer
      sources; and the "Disengaged," who are not interested in science, do not know
      much about it, harbor critical views toward it, and encounter it-if at all-mostly
      through television.

PMID- 29336219
TI  - Asymmetricity Between Sister Cells of Pluripotent Stem Cells at the Onset of
      Differentiation.
AB  - Various somatic stem cells divide asymmetrically; however, it is not known
      whether embryonic stem cells (ESCs) divide symmetrically or asymmetrically, not
      only while maintaining an undifferentiated state but also at the onset of
      differentiation. In this study, we observed single ESCs using time-lapse imaging
      and compared sister cell pairs derived from the same mother cell in either the
      maintenance or differentiation medium. Mouse ESCs were cultured on E-cadherin
      coated glass-based dishes, which allowed us to trace single cells. The
      undifferentiated cell state was detected by green fluorescent protein (GFP)
      expression driven by the Nanog promoter, which is active only in undifferentiated
      cells. Cell population analysis using flow cytometry showed that the peak width
      indicating distribution of GFP expression broadened when cells were transferred
      to the differentiation medium compared to when they were in the maintenance
      medium. This finding suggested that the population of ESCs became more
      heterogeneous at the onset of differentiation. Using single-cell analysis by time
      lapse imaging, we found that although the total survival ratio decreased by
      changing to differentiation medium, the one-live-one-dead ratio of sister cell
      pairs was smaller compared with randomly chosen non-sister cell pairs, defined as
      an unsynchronized cell pair control, in both media. This result suggested that
      sister cell pairs were more positively synchronized with each other compared to
      non-sister cell pairs. The differences in interdivision time (the time interval
      between mother cell division and the subsequent cell division) between sister
      cells was smaller than that between non-sister cell pairs in both media,
      suggesting that sister cells divided synchronously. Although the difference in
      Nanog-GFP intensity between sister cells was smaller than that between non-sister
      cells in the maintenance medium, it was the same in differentiation medium,
      suggesting asymmetrical Nanog-GFP intensity. These data suggested that ESCs may
      divide asymmetrically at the onset of differentiation resulting in heterogeneity.

PMID- 29336220
TI  - High Serum Cholesterol Is a Novel Risk Factor for Graves' Orbitopathy: Results of
      a Cross-Sectional Study.
AB  - BACKGROUND: Limited data suggest that treatment with statins is associated with a
      reduced risk of Graves' orbitopathy (GO) in patients with Graves' disease (GD),
      attributed to the anti-inflammatory rather than to the hypolipemic effects of
      these medications. The aim of the present study was to investigate whether there
      is an association between high cholesterol and GO. The primary outcome was the
      relation between GO and low-density lipoprotein (LDL)-cholesterol. The secondary
      outcomes were the relation between severity or activity (the clinical activity
      score [CAS]) of GO and LDL-cholesterol. METHODS: A cross-sectional investigation
      was conducted in consecutive patients with GD who came under the authors'
      observation to undergo radioiodine treatment, a stratification aimed at forming
      two distinct groups of patients under the same conditions. A total of 250
      patients were enrolled, 133 with and 117 without GO. Ophthalmological assessments
      and serum lipids measurements were performed. RESULTS: In multivariate analyses
      with correction for the duration of hyperthyroidism, a variable that differed
      between patients with respect to the presence or absence of GO, a correlation
      between the presence of GO and both total (p = 0.01) and LDL-cholesterol (p =
      0.02) was observed. In patients with hyperthyroidism lasting <44 months, total
      and LDL-cholesterol were higher (p = 0.01 and p = 0.008, respectively) among GO
      patients. In this subgroup, based on the presence/absence of GO, cutoff values
      were established for total (191 mg/dL) and LDL-cholesterol (118.4 mg/dL), above
      which an increased risk of GO was observed (total cholesterol relative risk:
      1.47; p = 0.03; LDL-cholesterol relative risk: 1.28; p = 0.03). GO severity and
      CAS did not correlate with serum lipids. However, CAS was found to be higher (p =
      0.02) in patients with high total cholesterol. When the analysis was restricted
      to untreated GO patients, a correlation was found between CAS and both total (p =
      0.04) and LDL-cholesterol (p = 0.03), after adjustment for GO duration.
      CONCLUSIONS: In patients with a short duration of hyperthyroidism, total and LDL
      cholesterol correlate with the presence of GO, suggesting a role of cholesterol
      in the development of GO. Depending on GO duration, total and LDL-cholesterol
      correlate with GO activity, suggesting a role of cholesterol in the clinical
      expression of GO.

PMID- 29336221
TI  - Sequelae of Tympanostomy Tubes in a Multihospital Health System.
AB  - Objectives Review the incidence of long-term sequelae after placement of
      tympanostomy tubes. Study Design Case series with chart review. Setting
      Multihospital network. Subjects Patients 0 to 3 years old undergoing tympanostomy
      tube (TT) placement. Methods A case series of 14,058 children between 2004 and
      2010 was reviewed. The patients were followed for 5 years to determine number of
      repeated tube placements, need for surgical removal of tubes, and presence of
      perforation requiring repair. Results The study cohort included 14,058 children
      who underwent TT placement. The mean age at time of procedure was 1.4 years. A
      total of 14.4% of patients required a second set of tubes within the 5 years of
      follow-up studied, and 4.6% required 3 or more sets. Three percent required
      removal of a tube, and this occurred at an average time of 34.2 +/- 17.6 months
      postplacement. In total, 5.1% had a resulting perforation after either tube
      extrusion or tube removal requiring myringoplasty. Conclusions The rate of
      multiple tube placements and myringoplasty and tympanoplasty to correct resulting
      perforations has yet to be studied in a single large population. This information
      allows for more detailed preoperative counseling to patients and families. Better
      characterization of these populations with accurate rates of sequelae can help to
      tailor treatment and preoperative counseling in the future.

PMID- 29336222
TI  - Implementing a Health Home: Michigan's Experience.
AB  - As the number of individuals in the United States with chronic conditions and the
      associated costs in caring for these individuals continues to rise, there is a
      need to transform how health care services are delivered. Under Section 2703 of
      the Affordable Care Act of 2010, the federal government provides state Medicaid
      programs the opportunity to improve care coordination for people with chronic
      conditions in a person-centered approach through the establishment of health
      homes. Given the complexity of care for Medicaid beneficiaries with chronic
      conditions, addressing the social determinants of health and providing integrated
      care are central to effectively improving health outcomes and generating cost
      savings. Although launching a health home model is a step toward improving care
      coordination and care management for high-risk individuals, there are myriad
      components to implementing such a program. The purpose of this article is to
      explain the process that Michigan policymakers undertook to implement its Section
      2703 Medicaid health home initiative, named the MI Care Team. The authors present
      lessons learned for policymakers and stakeholders in other states seeking to
      implement a Medicaid health home and explain how the nursing profession is
      integral for health homes.

PMID- 29336223
TI  - Assessment of safety culture among job positions in high-rise construction: a
      hybrid fuzzy multi criteria decision-making (FMCDM) approach.
AB  - The construction industry is known as one of the most dangerous industries, which
      not only requires sound operation of executive laws and regulations, but also
      necessitates the safety culture of all workers at workshops. Therefore, the aim
      of this research is to identify the factors of safety culture and ranking
      occupations in jobsites based on those factors in order to proactively improve
      the safety culture of construction projects and subsequently promote safety
      conditions and worksites. In this study, safety culture criteria are weighted by
      a combination of Fuzzy Decision Trail and Evaluation Laboratory and Fuzzy ANP
      methods. Next, different job positions in high-rise projects are ranked using the
      Fuzzy Technique for Order of Preference by Similarity to Ideal Solution method.
      Findings demonstrated that the project manager, site superintendent and
      supervisor occupations had the highest and labourers had the lowest level of
      safety culture in the high-rise construction industry. Furthermore, factors such
      as safety supervision and training must be considered more seriously in order to
      create a positive safety culture among workers.

PMID- 29336224
TI  - Treatment of a Klebsiella pneumoniae KPC cellulitis and gut decolonization with
      ceftazidime/avibactam in a migrant from Libya.
AB  - KPC-producing Klebsiella pneumoniae (KPC-Kp) is nowadays a global concern.
      Ceftazidime/avibactam is the most promising novel antibiotic combination
      available at the moment. We describe the case of a migrant with no risk factors
      for an infection due to multidrug resistant bacteria. He suffered from a KPC-Kp
      cellulitis and was treated with a ceftazidime/avibactam-meropenem-fosfomycin
      combination that not only eradicated the infection but also decontaminated his
      gut. Ceftazidime/avibactam-based treatment can be useful also in decontamination
      procedures.

PMID- 29336225
TI  - A robust likelihood approach to inference about the kappa coefficient for
      correlated binary data.
AB  - We construct a legitimate likelihood function for the agreement kappa coefficient
      for correlated data without specifically modelling all levels of correlation.
      This makes available the likelihood ratio test, the score test and other tools
      without the knowledge of the underlying distributions. This parametric robust
      likelihood approach applies to general clustered data scenarios. We provide
      simulations and real data analysis to demonstrate the advantage of the robust
      procedure.

PMID- 29336226
TI  - Identifying Metrics before and after Readmission following Head and Neck Surgery
      and Factors Affecting Readmission Rate.
AB  - Objectives Determine nationally representative readmission rates after head and
      neck cancer (HNCA) surgery and factors associated with readmission. Study Design
      Cross-sectional analysis of admissions database. Methods The 2013 Nationwide
      Readmissions Database was analyzed for HNCA surgery admissions and subsequent
      readmission within 30 days. The readmission rate, length of stay (LOS),
      disposition, mortality rate, and total charges were determined. Diagnoses and
      procedures upon readmission were quantified. Factors that were associated with
      readmission were determined. Results In total, 132,755 HNCA surgery inpatient
      admissions (mean age, 57.3 years; 52.2% male) were analyzed. Nationally
      representative metrics for HNCA surgery were mean LOS (4.4 +/- 0.1 days),
      disposition (home without services, 80.5%; home health care, 10.9%; and skilled
      facility, 6.6%), mortality rate (1.0% +/- 0.1%), and total charges ($53,106 +/-
      $1167). The readmission rate was 7.7% +/- 0.2% (mean readmission postoperative
      days, 17.1 +/- 0.1), with readmission LOS (5.6 +/- 0.1 days), mortality rate
      (3.7% +/- 0.3%), and total charges ($49,425 +/- $1548). The most common diagnoses
      at readmission included surgical complications (15.5%), mental health and
      substance abuse (13.1%), hypertension (12.8%), septicemia/infection (12.1%),
      gastrointestinal disease (11.3%), nutritional/metabolic disorders (10.1%),
      electrolyte abnormalities (8.5%), and esophageal disorders (8.1%). In
      multivariate analyses, male sex, increasing All Patients Refined Diagnosis
      Related Group (APR-DRG) severity score, and initial LOS were associated with
      readmission (odds ratio [95% confidence interval], 1.11 [1.04-1.20], 1.94 [1.77
      2.12], and 1.34 [1.22-1.48], respectively), whereas age and discharge location
      were not ( P = .361 and .482). Conclusion HNCA surgery readmission is associated
      with significant increases in services/skilled care on discharge, mortality, and
      additional total health care cost. This national analysis identifies common
      readmission diagnoses to target to prevent readmissions.

PMID- 29336227
TI  - Extracts from Lupinus albescens: antioxidant power and antifungal activity in
      vitro against phytopathogenic fungi.
AB  - Fungi are considered the most damaging microorganisms in agriculture. The
      indiscriminate use of chemical treatments in agricultural products causes the
      development of pest resistance and affects human health. An alternative to
      synthetic fungicides is the use of natural products such as plant extracts for
      the management of fungal diseases in plants. Extracts from different parts of
      Lupinus albescens (roots, stalks, leaves, and flowers) were obtained by
      extraction using supercritical carbon dioxide (CO2) or compressed liquefied
      petroleum gas (LPG). Thereafter, the antioxidant activity of each extract was
      measured, and the antifungal activity in vitro of extracts was evaluated against
      Fusarium oxysporum and Fusarium verticillioides. For a concentration of 5000
      mg/L, the half maximal inhibitory concentration (IC50) ranged from 29.25 MUg/mL
      to 192.96 MUg/mL. Antifungal tests showed that all matrices presented inhibitory
      effect against both fungi tested. The extracts obtained from roots by CO2 and LPG
      presented 70.1% and 65.1% inhibition against F. oxysporum, and 67.8% and 61.2%
      inhibition against F. verticillioides, respectively. These results suggest that
      the extracts obtained from L. albescens by extractions using supercritical CO2
      and compressed LPG might be a potential source of antioxidants and natural
      fungicides.

PMID- 29336228
TI  - The Multitheoretical List of Therapeutic Interventions - 30 items (MULTI-30).
AB  - OBJECTIVE: To develop a brief version of the Multitheoretical List of Therapeutic
      Interventions (MULTI-60) in order to decrease completion time burden by
      approximately half, while maintaining content coverage. Study 1 aimed to select
      30 items. Study 2 aimed to examine the reliability and internal consistency of
      the MULTI-30. Study 3 aimed to validate the MULTI-30 and ensure content coverage.
      METHOD: In Study 1, the sample included 186 therapist and 255 patient MULTI
      ratings, and 164 ratings of sessions coded by trained observers. Internal
      consistency (Chronbach's alpha and McDonald's omega) was calculated and
      confirmatory factor analysis was conducted. Psychotherapy experts rated content
      relevance. Study 2 included a sample of 644 patient and 522 therapist ratings,
      and 793 codings of psychotherapy sessions. In Study 3, the sample included 33
      codings of sessions. A series of regression analyses was conducted to examine
      replication of previously published findings using the MULTI-30. RESULTS: The
      MULTI-30 was found valid, reliable, and internally consistent across 2564 ratings
      examined across the three studies presented. CONCLUSION: The MULTI-30 a brief and
      reliable process measure. Future studies are required for further validation.

PMID- 29336229
TI  - Parasites of importance for human health on edible fruits and vegetables in
      Nigeria: a systematic review and meta-analysis of published data.
AB  - Contamination of edible fruits and vegetables is now a global public health issue
      despite their health benefits as non-pharmacological prophylaxis against chronic
      diseases. Studies that will harness the extent of parasitic contaminations will
      ensure public health protection. Here, the prevalence and distribution of
      parasites of importance for human health on fruits and vegetables in Nigeria were
      determined through a systematic review and meta-analysis of published data. The
      random-effects model was used to determine pooled prevalence estimate (PPE).
      Heterogeneity was evaluated by the Cochran's Q-test. Parasites overall PPE of
      32.4% (95% CI: 0.73, 0.91) was observed from 19 eligible studies reported across
      13 Nigerian states. Sub-groups PPEs ranged between 3.5% (95% CI: 0.45, 1.86) and
      58.5% (95% CI: 1.40, 4.09). A high degree of heterogeneity 97.53% (95% CI: 0.30,
      0.46, P: 0.000) was observed within studies and sub-groups. Cryptosporidium
      species were the most prevalent, while Ancylostoma duodenale and Ascaris
      lumbricoides had the widest geographical distribution. Pineapple (Prev: 41.3%,
      95% CI: 0.40, 0.75) and lettuce (Prev: 51.5%, 95% CI: 0.37, 0.68) recorded the
      highest level of parasitic contamination. Parasites of importance for human
      health are prevalent on edible fruits and vegetables in Nigeria. Prevalence
      estimates were highest in the South-eastern region and during the most recent
      decade. Adequate washing of fruits and vegetables, on-farm irrigation of
      vegetables using good sources of water and adequate hygiene by food handlers will
      help the general public to maximize the health benefits associated with the
      intake of fruits and vegetables while minimizing the risk of acquiring parasitic
      infections.

PMID- 29336230
TI  - Alterations of Global DNA Methylation and DNA Methyltransferase Expression in T
      and B Lymphocytes from Patients with Newly Diagnosed Autoimmune Thyroid Diseases
      After Treatment: A Follow-Up Study.
AB  - BACKGROUND: Dysregulated DNA methylation in lymphocytes has been linked to
      autoimmune disorders. The aims of this study were to identify global DNA
      methylation patterns in patients with autoimmune thyroid diseases and to observe
      methylation changes after treatment for these conditions. METHODS: A cross
      sectional study was conducted, including the following patients: 51 with newly
      diagnosed Graves' disease (GD), 28 with autoimmune hypothyroidism (AIT), 29 with
      positive thyroid autoantibodies, and 39 matched healthy volunteers. Forty GD
      patients treated with radioiodine or antithyroid drugs and 28 AIT patients
      treated with L-thyroxine were followed for three months. Serum free
      triiodothyronine, free thyroxine, thyrotropin, thyroid peroxidase antibodies,
      thyroglobulin antibodies, and thyrotropin receptor antibodies were assayed using
      electrochemiluminescent immunoassays. CD3+ T and CD19+ B cells were separated by
      flow cytometry for total DNA and RNA extraction. Global DNA methylation levels
      were determined by absorptiometry using a methylation quantification kit. DNA
      methyltransferase (DNMT) expression levels were detected by real-time polymerase
      chain reaction. RESULTS: Hypomethylation and down-regulated DNMT1 expression in T
      and B lymphocytes were observed in the newly diagnosed GD patients. Neither the
      AIT patients nor the positive thyroid autoantibodies patients exhibited
      differences in their global DNA methylation status or DNMT mRNA levels compared
      with healthy controls. Antithyroid drugs restored global methylation and DNMT1
      expression in both T and B lymphocytes, whereas radioiodine therapy affected only
      T cells. L-thyroxine replacement did not alter the methylation or DNMT expression
      levels in lymphocytes. The global methylation levels of B cells were negatively
      correlated with the serum thyroid peroxidase antibodies in patients with
      autoimmune thyroid diseases. CONCLUSIONS: Hyperthyroid patients with newly
      diagnosed GD had global hypomethylation and lower DNMT1 expression in T and B
      lymphocytes. The results provide the first demonstration that antithyroid drugs
      or radioiodine treatment restore global DNA methylation and DNMT1 expression with
      concurrent relief of hyperthyroidism.

PMID- 29336232
TI  - Wealth, Social Protection Programs, and Child Labor in Colombia: A Cross
      sectional Study.
AB  - This article has 3 main objectives: (1) to assess the prevalence of child labor
      in Colombia, (2) to identify factors associated with child labor, and (3) to
      determine whether social protection programs have an association with the
      prevalence of child labor in the country. Using a cross-sectional study with data
      from the Colombian Demographic and Health Survey 2010, a working child was
      defined as a child who worked during the week prior to the survey in an activity
      other than household chores. Through descriptive statistics, bivariate analysis,
      and multivariate regressions, it was found that child labor was associated with
      gender (boys were more likely to work), older age, ethnicity (children from
      indigenous communities were more likely to be workers), school dropout,
      disability (children with disabilities were less likely to be working),
      subsidized health social security system membership, and lower number of years of
      mother's schooling. Furthermore, the results of this study suggest that children
      beneficiaries of the subsidy Familias en Accion were less likely to be working
      and that social protection programs were more effective to reduce child labor
      when targeting the lowest wealth quintiles of the Colombian population.

PMID- 29336231
TI  - A Universal Classification System of Skin Substitutes Inspired by Factorial
      Design.
AB  - The complexity of the dermal layer of skin means that damage to this section can
      result in permanent impairment of function. Partial or total dermal loss is a
      feature of deep burns and chronic wounds such as pressure sores or diabetic
      ulcers. The issues posed by traditional skin grafts have led to substantial
      research being carried out in the fields of tissue engineering and biomaterials
      science to develop a vast array of alternative skin substitutes. Given the large
      number of different materials, manufacturing methods, and techniques for
      implementation described for artificial skin substitutes, many classification
      systems have been created to simplify their categorization. Some of these systems
      are oriented toward clinicians while others toward researchers. However, none
      address the needs of both groups and none are intuitive. The creation of an
      effective classification system would be particularly helpful in the regulation,
      distribution, organization, and selection of skin substitutes. The aim of this
      review is to examine existing methods of classification of skin substitutes, and
      to propose a new system that uses an algorithm that is inspired by factorial
      design. Our system allows multiple factors to be simultaneously investigated or
      in this case, described, since all skin substitutes possess multiple
      characteristics: (1) cellularity (acellular or cellular), (2) layering (single
      layer or bilayer), (3) replaced region (epidermis, dermis, or both), (4)
      materials used (natural, synthetic, or both), and (5) permanence (temporary or
      permanent). The factors and levels are combined into an algorithm where all the
      possible combinations are shown. The multifactorial and palindromic structure of
      our system should enable all users to quickly understand the makeup of a selected
      skin substitute, or search for a skin substitute depending on their specific
      requirements. We feel that our proposed classification can be used by clinicians
      and biomedical researchers alike, which should be an advantage given the
      multidisciplinary nature of the tissue engineering field and the science that
      underpins the development of skin substitutes. We also touch upon some of the
      state-of-the-art skin substitutes that are commercially available or under
      development to demonstrate how our new method of classification might work.

PMID- 29336234
TI  - Haemostaseological complication management in caval and iliac venous stenting.
AB  - Antiplatelet and anticoagulation therapy after venous stenting is still not
      standardized, data from randomized-controlled trials are missing. Rare
      prothrombotic disorders and nonresponsiveness to drugs must be taken into
      account. This case report demonstrates successful haemostaselogical complication
      management in recurrent rethromboses due to underlying clopidogrel resistance and
      low responsiveness to anticoagulation with dabigatran after endovascular stent
      reconstruction of chronic pelvic and caval vein occlusion in a patient with
      severe postthrombotic syndrome.

PMID- 29336235
TI  - Rapid Remission of Graves' Hyperthyroidism Without Thionamides Under
      Immunosuppressive Treatment for Concomitant Autoimmune Hepatitis.

PMID- 29336237
TI  - Masticatory function and oral stereognosis in bruxers.
AB  - OBJECTIVE: To compare the mastication and oral sensory function of individuals
      with and without sleep bruxism. METHODS: The sample comprised 60 volunteers, of
      which 30 were bruxers (mean age = 30.5 +/- 6.0) and 30 non-bruxers (mean age =
      28.6 +/- 3.3). Sleep bruxism was clinically diagnosed and confirmed using the
      Bruxoff(r) device. Mastication was evaluated according to swallowing threshold
      and masticatory efficiency. Swallowing threshold was determined from the median
      particle size of Optosil(r), obtained after an individualized number of
      masticatory cycles, which was first determined by chewing peanuts; masticatory
      efficiency was estimated by the sieving method. Oral stereognosis test was used
      to determine the oral sensory function. Variables were compared using one-way
      ANOVA (p < .05). RESULTS: The median particle size, masticatory efficiency, and
      oral sensory function did not differ significantly between bruxers and non
      bruxers (p > .05). CONCLUSION: Dentate adults present similar mastication and
      oral sensory function, despite the presence of sleep bruxism.

PMID- 29336236
TI  - Implementation of genomics research in Africa: challenges and recommendations.
AB  - BACKGROUND: There is exponential growth in the interest and implementation of
      genomics research in Africa. This growth has been facilitated by the Human
      Hereditary and Health in Africa (H3Africa) initiative, which aims to promote a
      contemporary research approach to the study of genomics and environmental
      determinants of common diseases in African populations. OBJECTIVE: The purpose of
      this article is to describe important challenges affecting genomics research
      implementation in Africa. METHODS: The observations, challenges and
      recommendations presented in this article were obtained through discussions by
      African scientists at teleconferences and face-to-face meetings, seminars at
      consortium conferences and in-depth individual discussions. RESULTS: Challenges
      affecting genomics research implementation in Africa, which are related to
      limited resources include ill-equipped facilities, poor accessibility to research
      centers, lack of expertise and an enabling environment for research activities in
      local hospitals. Challenges related to the research study include delayed
      funding, extensive procedures and interventions requiring multiple visits, delays
      setting up research teams and insufficient staff training, language barriers and
      an underappreciation of cultural norms. While many African countries are
      struggling to initiate genomics projects, others have set up genomics research
      facilities that meet international standards. CONCLUSIONS: The lessons learned in
      implementing successful genomics projects in Africa are recommended as strategies
      to overcome these challenges. These recommendations may guide the development and
      application of new research programs in low-resource settings.

PMID- 29336238
TI  - SIRT1-Regulated Abnormal Acetylation of FOXP3 Induces Regulatory T-Cell Function
      Defect in Hashimoto's Thyroiditis.
AB  - BACKGROUND: Hashimoto's thyroiditis (HT) is an autoimmune thyroid disease
      characterized by low expression of transcription factor Forkhead Box P3 (FOXP3)
      and functional deficiency of a cluster of differentiation regulatory T cells
      (Tregs). This study aimed to investigate the mechanism of Treg dysfunction in HT.
      METHODS: The number of CD4+CD25+FOXP3+ T cells was determined by flow cytometry.
      Expression of FOXP3 and Sirtuin type 1 (SIRT1) was evaluated by Western blot
      analysis. Acetylation of FOXP3 was analyzed by immunoprecipitation and Western
      blot analysis. The suppressive function of Treg was analyzed by the 5,6
      carboxyfluorescein diacetate succinimidyl ester (CFSE) assay. RESULTS: The
      percentage of CD4+CD25+FOXP3+ T cells, expression of FOXP3, and FOXP3 acetylation
      level in the HT group were significantly lower than in the control groups.
      Conversely, SIRT1 expression was significantly higher in the HT group than in the
      other two groups. After Ex-527 treatment, the CD4+CD25+FOXP3+ T cells percentage,
      FOXP3 expression, and FOXP3 acetylation level in the HT group were significantly
      increased. HT Tregs exhibited less suppressive activity, but Ex-527 treatment
      significantly increased their suppressive activity. CONCLUSIONS: The findings
      demonstrate that the reduced FOXP3 expression level and Treg function defect in
      HT patients are regulated by SIRT1-mediated abnormal FOXP3 acetylation. Ex-527
      may upregulate the FOXP3 acetylation level and subsequently increase the number
      and suppressive function of Treg cells.

PMID- 29336239
TI  - Early prognosis and predictor analysis for positive coronary angiography after
      out-of-hospital cardiac arrest (OHCA).
AB  - BACKGROUND: Key predictors of survival after OHCA have been described in the
      literature. Current guidelines recommend emergency angiography in patients
      without an obvious extra-cardiac cause of arrest. However, the value of this
      strategy is debated. Moreover, diagnosis of acute coronary ischaemia after OHCA
      remains challenging, especially in patients without ST-segment elevation.
      OBJECTIVES: The primary objective was to identify qualitative variables
      associated with an increased chance of 30-d survival after OHCA. The secondary
      objective was to identify predictors of 30-d survival among patients with
      ischaemic cardiomyopathy and patients without ST-segment elevation. Afterwards,
      we sought to identify parameters associated with acute coronary ischaemia and
      positive coronary angiography in patients without ST-segment elevation. METHODS:
      Retrospective single-centre study including 123 patients resuscitated from OHCA.
      Baseline characteristics, resuscitation settings and angiographic findings were
      analysed. RESULTS: The predictors of 30-d survival after OHCA included witnessed
      cardiac arrest, haemodynamic instability and coronary angiography. Convertible
      cardiac rhythm, history of coronary disease and presence of at least two
      cardiovascular risk factors were associated with acute coronary ischaemia.
      Predictors for a positive angiography in patients without ST-segment elevation
      included history of coronary disease, gender, diabetes, dyslipidaemia and
      presence of at least two cardiovascular risk factors (all p < .05). CONCLUSIONS:
      We identified qualitative predictors of 30-day survival after OHCA. Our findings
      suggest that the recognition of acute coronary ischaemia after OHCA might be
      improved. The identification of risk criteria may help to select the best
      candidates for emergency angiography.

PMID- 29336240
TI  - Treatment of anemia in patients with solid tumors receiving chemotherapy in
      palliative setting: usual practice versus guidelines.
AB  - Background Anemia is frequent in patients with cancer and is often
      multifactorial. Treatment depends on etiology and can consist of transfusions,
      intravenous iron (IV Fe), and/or erythropoiesis-stimulating agents (ESA). Several
      studies have shown that cancer-related anemia is undertreated. The aim of this
      study is to compare usual practice in a university hospital with the
      international guidelines. Methods Using the hospital and pharmacy informatics all
      adults (>=18 years), who received a treatment for anemia (transfusion, IV Fe,
      ESA) from February to August 2016 during palliative chemotherapy, were
      identified. Episodes of care were defined as the start of palliative chemotherapy
      up until 4 weeks after end of chemotherapy. After informed consent, relevant data
      in the episode of care were collected. Usual practice was compared to
      international guidelines adapted to Belgium reimbursement criteria. Results A
      total of 72 episodes of care were included. At initiation of chemotherapy, anemia
      was present in 59.7% of cases. Iron status was measured in 54.2% of all cases.
      Iron deficiency was found in 34.7% of patients. Only 52% of the iron deficient
      patents received IV Fe. Fifteen cases were considered eligible for ESA, six (40%)
      of these patients received an ESA. The most frequent treatments for anemia were
      transfusions (91.7%), followed by IV Fe (18.1%). Only 8.3% received an ESA.
      Conclusion Assessment for iron, Vitamin B12, and FA deficits are underused. We
      detected a high rate of transfusions. In contrast there is still a low use of IV
      Fe and ESA's. There has been no major improvement in the implementation of the
      international guidelines in the last decade. We estimate that in at least 16.7
      26.4% of our patients less to no transfusions would have been required, if
      guidelines were strictly followed.

PMID- 29336241
TI  - Generation of the Fluorescent HPV16 E7 Protein for Detection of Delivery In
      vitro.
AB  - BACKGROUND: Immunotherapies targeting the human papillomavirus (HPV) oncogenic
      proteins, E6 and E7, are effective to treat HPV-associated cervical malignancies.
      OBJECTIVE: The main objective of this study was to generate the fluorescent HPV16
      E7 protein for detection of delivery in vitro. METHODS: Two types of the fusion
      E7-GFP proteins (i.e., with or without linker) were expressed in different E.
      coli strains. Then, the efficiency of GFP and E7-GFP transfection was compared
      with FITC-antibody protein control using TurboFect reagent in the HEK-293T cell
      line. RESULTS: Our data indicated that both E7-GFP fusion proteins were
      efficiently produced in M15 E. coli strain, but not in BL21 or Rosetta strains.
      The E7-GFP fusion showed a clear band of ~ 50 kDa in SDS-PAGE. Moreover, the E7
      GFP protein maintained the fluorescent properties only when there was a distance
      between E7 and GFP genes, suggesting a promising potential to use GFP fusion
      protein in generating soluble form of protein. This fluorescent property was
      stable and could be detected in vitro. Moreover, the HEK-293T cells transfected
      by GFP/TurboFect and E7- GFP/TurboFect complexes demonstrated spreading green
      regions using fluorescent microscopy. Flow cytometry results showed that the GFP
      fluorescence was stable even at 24 h post-transfection. CONCLUSION: Briefly, the
      E7-GFP fusion protein with linker can be useful for the development of protein
      vaccines against HPV16 infections and detection in vivo.

PMID- 29336242
TI  - The Influence of Fatty Acids on Metoprolol - Human Serum Albumin Interaction in
      Low Affinity Binding Sites: A Multifactorial NMR Approach.
AB  - BACKGROUND: Metoprolol (MTP) is a cardio-selective beta1-blocker used in
      hypertension, angina pectoris and chronic heart failure therapies. Serum albumin
      is the most frequently occurring protein in blood plasma. The binding of ligands
      to human serum albumin (HSA) has an important effect on pharmacokinetics and
      final clinical effects. OBJECTIVE: The objectives of this study included a
      detailed analysis of metoprolol - serum albumin interactions in low affinity
      binding sites, on the surface or within the hydrophobic subdomain of a
      macromolecule, as well as an analysis of the competition between MTP and fatty
      acids in binding with protein. METHODS: The analysis of the drug-albumin
      interaction was based on the observed chemical shifts in combination with
      correlation Times (T1 -1 = tau) [1/s], 2D NOESY 1H NMR spectra and association
      constants Ka [M-1]. For the determination of chemical shifts sigma [ppm],
      relaxation times T1 [s] and for the NOESY experiment, the final concentrations of
      MTP and albumins (in the presence (HSA) and absence of fatty acids (dHSA)) were 5
      x 10-3 M and 2 x 10-5 M - 4.55 x 10-4 M, respectively. In order to calculate the
      association constants, the final concentrations of MTP and both HSA and dHSA were
      2.75 x 10-3 M - 6.25 x 10-2 M and 2.5 x 10-4 M, respectively. For the analysis,
      the MTP proton resonances of aliphatic H17, aromatic (H2/H6 and H3/H5) and the
      methoxy group H14 were chosen. RESULTS: Changes in the values of the 1H NMR
      chemical shift [ppm] are evidence of interaction between MTP, fatted (HSA) and
      defatted (dHSA) human serum albumin. With an increase of albumin concentration,
      changes in the chemical shift values were observed for the aromatic protons H2/H6
      (Deltasigma = 0.013 ppm and 0.018 ppm) and H3/H5 (Deltasigma = 0.015 ppm and
      0.019 ppm), the aliphatic proton H17 (Deltasigma = 0.018 ppm and 0.022 ppm) and
      the aliphatic protons of the methoxy group H14 (Deltasigma = 0.019 ppm and 0.022
      ppm) for dHSA and HSA, respectively. Greater changes in chemical shifts in the
      presence of fatty acids (FA) were observed. Changes in the correlation times of
      MTP aromatic H2/H6 (Deltatauc = 0.224 1/s and 0.189 1/s) and H3/H5 (Deltatauc =
      0.269 1/s and 0.210 1/s), aliphatic from the methoxy group H14 (Deltatauc = 0.472
      1/s and 0.271 1/s) and aliphatic H17 protons (Deltatauc = 0.178 1/s and 0.137
      1/s) for dHSA and HSA systems, respectively. It confirms the interaction between
      the drug and albumin are evidence for the dynamics of the process. In the
      presence of FA the relaxation time of all analyzed MTP proton resonance signals
      significantly increases (due to the decrease of correlation time). This
      phenomenon is due to the increase of electron density in the MTP protons'
      surroundings. Association constants for the MTP-dHSA complex in the low affinity
      site range between 0.29 x 102 M-1 and 0.47 x 102 M-1. The presence of FA results
      in a two to three-fold increase of the Ka values of protons from aromatic (H2/H6
      and H3/H5), aliphatic H17 and methoxy (H14) groups. In 2D NOESY spectra proton
      magnetization transfer was observed between cysteine (Cys-34) and aromatic H3/H5
      and H2/H6 protons. Cross-peaks were also observed between cysteine and aliphatic
      protons from the methoxy group. CONCLUSION: The selective changes in sigma [ppm]
      and tauc [1/s] values indicated the unequal participation of chemical groups of
      MTP in the interaction with HSA and dHSA. The data obtained suggest that the
      presence of fatty acids increases the accessibility of low affinity sites of
      serum albumin to MTP, which results in the higher affinity of albumin towards the
      drug. The results showed that the main binding site of MTP and fatty acid is
      probably a low affinity site in subdomain IB, where Cys-34 can be located.

PMID- 29336243
TI  - Identification of In-Vitro Red Fluorescent Protein with Antipathogenic Activity
      from the Midgut of the Silkworm (Bombyx Mori L.).
AB  - BACKGROUND: The midgut of silkworm (Bombyx mori L.) plays an important role as a
      natural barrier and source of innate immunity. We had purified the novel red
      fluorescent protein (RFP) from the midgut of the silkworm Bombyx mori L. and
      bioassay studies confirmed RFPs possess antiviral, antifungal and antibacterial
      properties. N-terminal sequence of RFP analysis predicted chbp gene and it
      belongs to lipocalin gene family and is known to involve in anti-pathogenic
      activities. OBJECTIVE: The main objective of this study was to purify RFP from
      the midgut of Kolar Gold silkworm and confirm its antimicrobial activity.
      METHODS: For isolation of RFP, midgut juice was collected by brief exposure to
      chloroform vapours to fifth instar Kolar Gold silkworm larvae. Juice was purified
      by 40 % ammonium sulfate precipitation and purified by gel filtration
      chromatography (GFC) and fractions with fluorescence red under Ultra violet (UV)
      were collected. Molecular weight and purity of RFP was identified using PAGE,
      MALDI-TOF and HPLC. Antimicrobial property of purified RFP against BmNPV,
      Escherichia coli, Klebsiella pneumonia, Bacillus subtilis and Phytophthora meadii
      was performed. N-terminal sequencing of RFP was performed using Edman degradation
      method. Using ten amino acid sequence, using default parameter BLAST search was
      performerd. From the fifth day old fifth instar silkworm midgut mRNA was isolated
      and cDNA was synthesized using oligo-dt primer and amplification of ChBP gene was
      carried out by using cDNA as the template and ChBP gene specific primers. chbp
      protein sequence as a input built the homology model by using SWISS-MODEL.
      RESULTS: RFP was purified by 40 % ammonium sulfate precipitation and gel
      filtration chromatography (GFC) and fractions with fluorescence red under Ultra
      violet (UV) were collected and SDS - PAGE revealed a size of 40 kDa. RFP purified
      by GFC was further reconfirmed by HPLC with a single peak with a retention time
      of 8.755 min. MALDI-TOF produced a peak at a molecular mass of 40 kDa. RFP from
      the midgut juice showed antiviral activity against the silkworm virus BmNPV,
      antibacterial activity against Escherichia coli, Klebsiella pneumonia, Bacillus
      subtilis and Phytophthora meadii. N-terminal sequencing of RFP by Edman
      degradation method sequenced TQTIETDYWV amino acids and BLAST analysis predicted
      the Chlorophyllide-a Binding Protein (chbp) with B. mori. PCR product was
      sequenced and obtained 911bp nucleotides encoding 302 amino acid residues and
      deposited with the accession number KX186723 in NCBI. Sequence analysis revealed
      Chbp belongs to lipocalin gene family and known to involve in antiviral,
      antifungal and anti-bacterial properties. Chbp gene homology model was predicted
      using crystal structure of insecticyanin A from the tobacco hornworm as a
      template. CONCLUSION: Our results indicated RFP present in midgut juice of 5th
      instar larvae of kolar gold silkworm. We have purified novel RFP with molecular
      mass of 40 kDa and showed its antipathogenic activities. Chbp gene synthesises
      RFP and further it could be utilized for agriculture and pharmaceutical industry.

PMID- 29336244
TI  - Editorial: Signal Proteins Involved in Glucose and Lipid Metabolism Regulation.

PMID- 29336245
TI  - The Role of Colchicine in Pericardial Syndromes.
AB  - BACKGROUND: Colchicine is an old drug originally employed for the treatment of
      inflammatory disorders such as acute gout and familiar Mediterranean fever.
      METHODS: In the past few decades, colchicine has been at the forefront of the
      pharmacotherapy of several cardiac diseases, including acute and recurrent
      pericarditis, coronary artery disease, prevention of atrial fibrillation and
      heart failure. In this review, we have summarized the current evidence based
      medicine and guidelines recommendations in the specific context of pericardial
      syndromes. RESULTS: Colchicine has been firstly engaged in the treatment of
      recurrent pericarditis of viral, idiopathic and autoimmune origin. Shortly
      thereafter colchicine use has been expanded to the primary prevention of
      recurrences in patients with a first episode of pericarditis depicting similarly
      good results. The acquisition of high quality scientific data in the course of
      time from prospective randomized placebo-controlled trials and metanalyses have
      established colchicine as first line treatment option in acute and recurrent
      pericarditis, on top of the conventional treatment. The only concerns related to
      the use of colchicine are the side effects (mainly gastrointestinal intolerance)
      which although generally not serious, may account for treatment withdrawal in
      some cases. CONCLUSION: Colchicine has been established as a first line
      medication in the treatment of acute (first episode) and recurrent pericarditis
      on top of the conventional treatment as well as for the prevention of
      postpericardiotomy syndrome. It depicts a good safety profile with
      gastrointestinal intolerance being the most common side effect.

PMID- 29336246
TI  - The Role of Colchicine in the Prevention of Cerebrovascular Ischemia.
AB  - INTRODUCTION: Despite the proven efficacy of anti-thrombotic, lipid-lowering,
      anti-hypertensive therapies and lifestyle modification changes for secondary
      ischemic stroke prevention, the risk of recurrent stroke, coronary events and
      vascular death remains substantial even for patients treated with high rates of
      established secondary preventive medications. METHODS: In the present review, we
      summarize available literature data on the association between systemic
      inflammation and symptomatic atherosclerosis including recurrent cerebral
      ischemia. We also highlight the potential role of colchicine in the suppression
      of atherosclerosis-induced inflammation, plaque stabilization and thromboembolism
      prevention. RESULTS: Accumulating evidence suggests that inflammation is of key
      importance in the pathophysiology of atherosclerotic plaque de-stabilization and
      thromboembolism, with inflammatory cells being involved in all stages of
      atherosclerosis development. Therefore, anti-inflammatory therapies targeting the
      atherosclerotic plaque inflammation may be important contributors in plaque
      stabilization and in the prevention of thromboembolic events. Colchicine is known
      to have multiple anti-inflammatory properties including inhibition of microtubule
      polymerization, leading to reduced secretion in monocyte-macrophages. Currently
      the randomized controlled CONVINCE trial is enrolling stroke patients to evaluate
      the effect of a daily low-dose of colchicine in reducing the rate of recurrent
      stroke and major vascular events. CONCLUSION: Inflammatory pathways seem to be
      key mediators in the development of atherosclerotic process, atheromatous plaque
      destabilization and thromboembolism. Colchicine as a novel therapeutic agent
      could be a safe and effective inhibitor of the inflammation cascade in patients
      with extra- or intracranial atherosclerosis or arteriolosclerosis, resulting in
      reduced vascular events.

PMID- 29336247
TI  - The Role of Colchicine in the Treatment of Autoinflammatory Diseases.
AB  - Colchicine has been longstanding and widely used for the treatment of acute gout
      flares and prevention of gout relapses. Its use has been extended to a series of
      autoinflammatory diseases, such as familial Mediterranean fever and more recently
      to periodic fever with aphthous stomatitis, pharyngitis and adenitis, Behcet's
      disease and idiopathic recurrent acute pericarditis. In this review, we summarize
      current indications of colchicine use, discuss its pharmacokinetics and mechanism
      of action and examine its use in the treatment of autoinflammatory diseases.
      Further understanding of the underlying mechanisms of the latter conditions as
      well as identification of the therapeutic efficacy and treatment target of
      colchicine may lead to more effective management of these diseases.

PMID- 29336248
TI  - Immunotheraphy in Allergic Diseases.
AB  - The prevalence of allergic diseases is increasing worldwide. It is estimated that
      more than 30% of the world population is now affected by one or more allergic
      conditions and a high proportion of this increase is in young people. The
      diagnosis of allergy is dependent on a history of symptoms on exposure to an
      allergen together with the detection of allergen-specific IgE. Accurate diagnosis
      of allergies opens up therapeutic options. Allergen specific immunotherapy is the
      only successful disease-modifying therapy for IgE-mediated allergic diseases. New
      therapeutic strategies have been developed or are currently under clinical
      trials. Besides new routes of administration, new types of allergens are being
      developed. The use of adjuvants may amplify the immune response towards tolerance
      to the antigens. In this review, we analyze different antigen-specific
      immunotherapies according to administration route, type of antigens and
      adjuvants, and we address the special case of food allergy.

PMID- 29336249
TI  - Mutations of Nuclear and Mitochondrial Genomes as Potential Targets for the
      Treatment of Metabolic Syndrome.
AB  - In addition to external factors, such as exercise, food and the environment,
      genetic predisposition makes great contribution to the development of metabolic
      disorders and cardiovascular disease. This review is aimed to examine the genetic
      basis of complex metabolic disorders conventionally described as "metabolic
      syndrome" (MetS), with the special focus on currently known mutations in the
      nuclear and mitochondrial genomes, which are associated with both the individual
      components of MetS and combinations thereof, and also on the studies of the
      relationship of MetS phenotype as a binary trait. The defects in the
      mitochondrial genome should be considered as one of the possible genetic reasons
      leading to MetS. It is known that mitochondrial dysfunction is closely associated
      with metabolic disorders, as mitochondria are the center of energy metabolism.
      Consequently, the changes in mitochondrial genes and their functions affect
      regulation of metabolism. Until now, the role of mitochondrial DNA damage in the
      development of cardiovascular diseases, age-related and metabolic disorders is
      still poorly understood. The results of performed studies would help assessing
      the role of mitochondrial DNA mutations in susceptibility to metabolic syndrome
      and related metabolic diseases.

PMID- 29336250
TI  - Colchicum Genus in the Writings of Ancient Greek and Byzantine Physicians.
AB  - The plants of the Colchicum family were known during the archaic period in Greece
      for their deleterious properties. Later on, they were used for the treatment of
      podagra. The treatment was introduced by the ancient Greek physicians and passed
      on to the Byzantine and Arabian physicians to endure until nowadays. The first
      plant was most probably named "Medea" from the notorious Colchican witch. As the
      most common member of the family blossoms in autumn, the plant was named
      Colchicum autumnale. Various nominations were also used, such as Ephemeron,
      Hermodactyl, Anima articulorum and Surugen. Our article discusses them, while at
      the same time presents the most notable authorities who have used Colchicum
      plants in herbal medicine and toxicology.

PMID- 29336251
TI  - Isolating Colchicine in 19th Century: An Old Drug Revisited.
AB  - Colchicine is a tricyclic alkaloid extracted from the herbaceous plant Colchicum
      autumnale. Known since antiquity for its therapeutic efficacy in the treatment of
      gout, colchicine was reintroduced in 19th century pharmacopeia, thanks to the
      work of the French chemists and pharmacists Pierre-Joseph Pelletier (1788-1842)
      and Joseph Bienaime Caventou (1795-1877) who in 1819, isolated a peculiar
      substance in the roots of Colchicum autumnale. In 1833, the substance was further
      analyzed by the German pharmacist and chemist Philipp Lorenz Geiger (1785-1836),
      who coined the name colchicine. In 1884, the French pharmacist Alfred Houde (1854
      1919) produced for the first time pure crystallized colchicine in granules of
      1milligram which is still sold under this trade name in several countries. In the
      last two centuries, colchicine's indications were furthermore expanded. From anti
      gout drug during antiquity and a diuretic in 19th century, colchicine is
      currently administered in several affections such as Adamantiades-Behcet's
      disease, familial Mediterranean fever, pericarditis and atrial fibrillation.

PMID- 29336252
TI  - Colchicine in Gout: An Update.
AB  - Despite the fact that colchicine is by far the most ancient treatment for gout,
      new data are still being gathered. In gout, colchicine's ability to block
      polymerization of tubulin prevents the activation of the inflammasome. Efficacy
      of colchicine for the treatment of gout flares has been demonstrated only
      recently by a randomized- controlled trial, but it still has not been compared to
      other drugs. Use of colchicine is impaired by the impact of underlying comorbid
      conditions and drug interactions that can considerably modify its
      pharmacokinetics and pharmacodynamics. This manuscript reviews the state-of-the
      art of colchicine in gout, from its known mechanisms of action to its effects,
      wanted and unwanted, expected and unexpected.

PMID- 29336253
TI  - Colchicine in Post-operative Atrial Fibrillation: A Review.
AB  - Post-operative atrial fibrillation (POAF) is a frequent entity increasing
      hospitalization duration, stroke and mortality. In the recent years, a few
      studies have sought to investigate the potential effect of colchicine in POAF
      prevention after cardiac surgery or catheter pulmonary vein isolation for AF. In
      the present review article, we intend to provide a synopsis of clinical practice
      guidelines, summarize and critically approach current evidence for or against
      colchicine as a means of POAF prevention.

PMID- 29336254
TI  - Colchicine in Neurosurgery.
AB  - BACKGROUND: Colchicine is an ancient drug. Many uses have been reported in
      medical books and reports through the centuries. Currently the understanding of
      its mechanism of action has opened new horizons to its use. OBJECTIVE: This
      article aims to discuss the use of colchicine in various neurosurgical
      conditions. METHODS: A pubmed database and clinical trials search was performed,
      using the key words "colchicine", "Neurosurgery", "low back pain", "stroke" and
      glioma". RESULTS: Various reports were found contemplating the use of colchicine
      in chronic low-back pain. The effect of the drug on neutrophil chemotaxis and its
      role as an anti-inflammatory agent has been the main argument upon which such use
      of colchicine has been structured. These characteristics have been the key to
      initiate colchicine as a preventive agent in vascular conditions. Furthermore, as
      colchicine is an antimitotic drug, it is currently being studied as a potential
      anti-glioma agent. However, the narrow therapeutic index of the drug is a
      discouraging factor in clinical application of colchicine in these entities.
      Therefore, colchicine derivatives that can exert the same effectiveness in lower
      doses are being studied, forming a new direction in colchicine use. CONCLUSION:
      Colchicine is a drug that over the years has shown promising results in certain
      neurosurgical entities. Its derivatives or potential colchicine-like agents might
      have a more significant place in neurosurgical practice.

PMID- 29336255
TI  - Fast Screening Technology for Drug Emergency Management: Predicting Suspicious
      SNPs for ADR with Information Theory-based Models.
AB  - OBJECTIVE: The genetic polymorphism of Cytochrome P450 (CYP 450) is considered as
      one of the main causes for adverse drug reactions (ADRs). In order to explore the
      latent correlations between ADRs and potentially corresponding single-nucleotide
      polymorphism (SNPs) in CYP450, three algorithms based on information theory are
      used as the main method to predict the possible relation. METHODS: The study uses
      a retrospective case-control study to explore the potential relation of ADRs to
      specific genomic locations and single-nucleotide polymorphism (SNP). The genomic
      data collected from 53 healthy volunteers are applied for the analysis, another
      group of genomic data collected from 30 healthy volunteers excluded from the
      study are used as the control group. The SNPs respective on five loci of
      CYP2D6*2,*10,*14 and CYP1A2*1C, *1F are detected by the Applied Biosystem 3130xl.
      The raw data is processed by ChromasPro to detect the specific alleles on the
      above loci from each sample. The secondary data are reorganized and processed by
      R combined with the reports of ADRs from clinical reports. Three information
      theory based algorithms are implemented for the screening task: JMI, CMIM, and
      mRMR. If a SNP is selected by more than two algorithms, we are confident to
      conclude that it is related to the corresponding ADR. The selection results are
      compared with the control decision tree + LASSO regression model. RESULTS: In the
      study group where ADRs occur, 10 SNPs are considered relevant to the occurrence
      of a specific ADR by the combined information theory model. In comparison, only 5
      SNPs are considered relevant to a specific ADR by the decision tree + LASSO
      regression model. In addition, the new method detects more relevant pairs of SNP
      and ADR which are affected by both SNP and dosage. This implies that the new
      information theory based model is effective to discover correlations of ADRs and
      CYP 450 SNPs and is helpful in predicting the potential vulnerable genotype for
      some ADRs. CONCLUSION: The newly proposed information theory based model has
      superiority performance in detecting the relation between SNP and ADR compared to
      the decision tree + LASSO regression model. The new model is more sensitive to
      detect ADRs compared to the old method, while the old method is more reliable.
      Therefore, the selection criteria for selecting algorithms should depend on the
      pragmatic needs.

PMID- 29336256
TI  - Mushrooms as Potent Sources of New Biofungicides.
AB  - BACKGROUND: Microfungi are causal agents of numerous diseases and disorders of
      agricultural plants, farm mushrooms and animals as well as human, which results
      are serious global reduction of the food amount, decrease of life quality, the
      severe life-threatening diseases and enormous economic losses. METHODS: In spite
      of organism innate ability to combat against pathogens, in invasions of some
      pathogens, support of additional antimycotic agents to defence system is
      required. Nowadays, common "fighters" against the microfungi are numerous
      synthetic fungicides that, besides benefits, have also side effects on host and
      environment and can cause the development of fungicide resistance in the
      pathogens. Therefore, the creation of new natural fungicides with different modes
      of action, strengthening the defense system and increase of organism resistance
      to pathogens are the main requirements of modern society. RESULTS: Numerous
      mushrooms produce chemically various intra- and extracellular metabolites with
      antifungal potential, among which the most potent ones are polysaccharides,
      proteins, and phenolic compounds. They act as immunostimulators, inhibitors of
      pathogen development and virulence and/or activators of pathogens' autolytic
      system. CONCLUSION: Therefore, mushroom-based antimycotic agents could be
      successfully applied in the diseases treatments as accessories or alternatives to
      commercial therapies and in such a way contribute to environmentally friendly
      combat against pathogens, i.e. decrease or complete substitution of commercial
      synthetic fungicides with natural ones.

PMID- 29336257
TI  - Medium Optimization for Recombinant Soluble Arginine Deiminase Expression in
      Escherichia coli Using Response Surface Methodology.
AB  - OBJECTIVE: Optimization of the medium for recombinant arginine deiminase
      production in E. coli was performed using response surface methodology. This is
      the first study of optimization of recombinant arginine deiminase production in
      E. coli by the use of response surface methodology. METHODS: A Mycoplasm arginine
      deiminase gene was computationally optimized and inserted into pET-3a (+)
      expression vector. The synthetic pET3a-arginine deiminase construct was cloned
      and overexpressed in E. coli. The effect of glucose, NH4Cl and MgSO4.7H2O
      concentrations on the expression of intracellular soluble arginine deiminase was
      investigated using central composite design (CCD). RESULTS: The maximum arginine
      deiminase activity (U/mL) was obtained in optimal concentrations g/L of glucose,
      6.6; NH4Cl, 1.81; MgSO4.7H2O, 0.94; KH2PO4, 3.0; Na2HPO4, 6.78; NaCl, 0.5; CaCl2,
      0.1 mL/L (1M), which was about 6.6 fold higher than that in M9 standard medium.
      CONCLUSION: The obtained result can be utilized for large-scale production of
      this enzyme and related recombinant protein.

PMID- 29336258
TI  - Association of Thrombospondin-1 (N700S) and Thrombospondin-4 (A387P) Gene
      Polymorphisms with the Incidence of Acute Myocardial Infarction in Egyptians
AB  - BACKGROUND: Thrombospondin (TSP) 1 and 4 are extracellular matrix glycoproteins
      that me-diate cell proliferation, platelet aggregation and inflammatory response.
      Conflicting data addressed thepossible contribution of TSP-1 and TSP-4 gene
      polymorphisms to acute myocardial infarction (AMI). OBJECTIVE: Our study aimed to
      examine the association of TSP-1 (N700S) and TSP-4 (A387P) geneticvariants with
      the incidence of AMI in Egyptians. It also correlated TSP-1 variants to TSP-1 and
      TNF-alphaserum concentrations while TSP-4 variants to IL-8 concentration
      identifying TSPs' contribution to vascular inflammation. METHODS: Genotyping was
      done in 214 subjects; 114 AMI patients and 100 controls using PCR-RFLPanalysis.
      Serum Tsp-1, TNF-alpha and IL-8 levels were measured by ELISA assay. RESULTS: For
      TSP-4, (GC and CC) genotype distribution and the (C) allele frequency were
      significantlyhigher in AMI patients than controls (p = 0.0186), (p = 0.0117)
      respectively. In contrast, TSP-1 genotypesand allele frequencies showed no
      significant difference between AMI and controls (p = 0.7124 and p =0.7201,
      respectively). Serum TSP-1, TNF-alpha and IL-8 concentrations were significantly
      elevated in AMIcompared to controls (p = 0.0146, p < 0.0001 and p = 0.0057)
      respectively. Serum IL-8 levels had a significant difference among TSP-4
      genotypes (p= 0.0368), being highest in the mutant C allele. SerumTSP-1 and TNF
      alpha concentrations showed no significant difference among TSP-1 genotypes, but
      therewas a positive correlation between both concentrations in AMI patients (p =
      0.0014), (r = 0.4125). CONCLUSION: TSP-4 A387P polymorphism, but not TSP-1
      polymorphism, is an independent risk factorfor AMI in the Egyptians.

PMID- 29336259
TI  - p53 as the Focus of Gene Therapy: Past, Present and Future.
AB  - BACKGROUND: Several gene deviations can be responsible for triggering oncogenic
      processes. However, mutations in tumour suppressor genes are usually more
      associated to malignant diseases, with p53 being one of the most affected and
      studied element. p53 is implicated in a number of known cellular functions,
      including DNA damage repair, cell cycle arrest in G1/S and G2/M and apoptosis,
      being an interesting target for cancer treatment. OBJECTIVE: Considering these
      facts, the development of gene therapy approaches focused on p53 expression and
      regulation seems to be a promising strategy for cancer therapy. RESULTS: Several
      studies have shown that transfection of cancer cells with wild-type p53
      expressing plasmids could directly drive cells into apoptosis and/or growth
      arrest, suggesting that a gene therapy approach for cancer treatment can be based
      on the re-establishment of the normal p53 expression levels and function. Up
      until now, several clinical research studies using viral and non-viral vectors
      delivering p53 genes, isolated or combined with other therapeutic agents, have
      been accomplished and there are already in the market, therapies based on the use
      of this gene. CONCLUSION: This review summarizes the different methods used to
      deliver and/or target the p53 as well as the main results of therapeutic effect
      obtained with the different strategies applied. Finally, the ongoing approaches
      are described, also focusing on the combinatorial therapeutics to show increased
      therapeutic potential of combining gene therapy vectors with chemo or
      radiotherapy.

PMID- 29336260
TI  - Adipocytes and Abdominal Aortic Aneurysm: Putative Potential Role of Adipocytes
      in the Process of AAA Development.
AB  - BACKGROUND: Adipose tissue plays a role in the storage of excess energy as
      triglycerides (TGs). Excess fat accumulation causes various metabolic and
      cardiovascular diseases. It has been reported that ectopic fat deposition and
      excess TG accumulation in non-adipose tissue might be important predictors of
      cardiometabolic and vascular risk. For example, ectopic fat in perivascular
      tissue promotes atherosclerotic plaque formation in the arterial wall. OBJECTIVE:
      Recently, it has been reported that ectopic fat (adipocyte) in the vascular wall
      of an abdominal aortic aneurysm (AAA) is present in both human and experimental
      animal models. The pathological significance of adipocytes in the AAA wall has
      not been fully understood. In this review, we summarized the functions of
      adipocytes and discussed potential new drugs that target vascular adipocytes for
      AAA treatment. RESULT: Previous studies suggest that adipocytes in vascular wall
      play an important role in the development of AAA. CONCLUSION: Adipocytes in the
      vascular wall could be novel targets for the development of AAA therapeutic
      drugs.

PMID- 29336261
TI  - Formulation and Investigation of a Lipid Based Delivery System Containing
      Antimicrobials for the Treatment of Periodontal Disease.
AB  - BACKGROUND: Periodontitis is a chronic inflammatory disease, which affects the
      supporting tissues of the teeth, and without proper treatment it may lead to
      tooth loss. Antibiotics - administered orally - have been widely used in the
      treatment of periodontitis. With the conventional administration routes, adequate
      drug levels cannot be reached in the periodontal pockets and oral application of
      antimicrobials could lead to side effects. Drug delivery systems containing
      antibiotics, administered at the site of infection, could possibly help eliminate
      pathogen bacteria and treat periodontitis. OBJECTIVE: The aim of the recent study
      was to create a locally swellable, biodegradable, biocompatible, mucoadhesive,
      lipophilic drug delivery system containing antimicrobial drugs which softens at
      body temperature, accommodate to the shape of the periodontal pocket and can
      provide extended drug release for at least one week. METHODS: During the
      formulation, thermoanalytical, consistency, wettability, swelling, degradation
      and drug release studies were applied to determine the ideal ratios of lipid
      bases, structure-building components and surface active agent concentrations.
      RESULTS AND DISCUSSION: The structure-building component cetostearyl alcohol
      appeared to be the most convenient, thanks to its wettability and mechanical
      properties, which led to controlled drug release. With the use of ideal
      concentrations of components (10% surfactant, 40% structure-building component,
      32 % lipid base, 15% antimicrobial agent and 3% polymer), sustained drug release
      can be provided up to nearly 3 weeks.

PMID- 29336262
TI  - Ethosomes as Novel Vesicular Carrier: An Overview of the Principle, Preparation
      and its Applications.
AB  - BACKGROUND: In the study of lipid vesicular carriers in permeation enhancement of
      drug molecules across skin after the success story of liposomes, ethosomes are a
      recent addition. There are a number of published reviews but still, there is a
      lack of reviews representing various aspects in a systematic way with a detailed
      description of current research works. This review serves to fill this deficiency
      along with special emphasize on its preparation methods and applications.
      METHODS: Information was collected from previously published literatures which
      were represented after analysis in terms of various aspects such as principles,
      composition, preparation, mechanism of penetration, modified forms,
      characterization, marketed preparations and its applications. RESULT: This review
      is represented in an informative and easily understandable way. Basic principles
      and background were covered in the introduction section. Composition section
      contains the basic components of formulations along with the impact of various
      parameters on the characterization of the ethosome. A detailed discussion of all
      the methods along with their own utility is elaborately provided. Various aspects
      of characterization studies of ethosomes are also discussed. Therapeutic and
      cosmetic applications of ethosomes are also outlined here. CONCLUSION: In spite
      of having a excellent permeation-enhancing and targeted drug release profile,
      ethosome suffers from limited commercialization. Various challenges regarding
      their commercialization and product development are also discussed in this review
      with an objective of acting as a directional route for the researchers.

PMID- 29336263
TI  - In vitro Methods for In vitro-In vivo Correlation (IVIVC) for Poorly Water
      Soluble Drugs: Lipid Based Formulation Perspective.
AB  - A great number of new drug candidates identified from the discovery pipeline are
      poorly water soluble, which is a drawback to bring such candidates into the
      pharmaceutical market. Formulating these compounds as self
      emulsifying/microemulsifying/ nanoemulsifying drug delivery systems
      (SEDDS/SMEDDS/SNEDDS) within lipid based formulations is of growing interest.
      Some of the recent studies have resulted in commercial products that provided
      improved bioavailability and dissolution due to the better dispersion properties
      of SEDDS/SMEDDS/SNEDDS. An ongoing challenge that the pharmaceutical industry is
      facing is identifying in vitro tests that are needed in order to predict the
      behavior of dosage forms in the GI tract. The goal of the current review is to
      present the various levels of in vitro-in vivo correlations (IVIVCs) and to
      provide tools on the utilization of the IVIVCs in product development and
      optimization of SEDDS/SMEDDS/SNEDDS.

PMID- 29336264
TI  - Taxifolin: Evaluation Through Ex vivo Permeations on Human Skin and Porcine
      Vaginal Mucosa.
AB  - BACKGROUND: Taxifolin (TAX) is a flavonoid that has numerous pharmacological
      properties, including an antioxidant ability superior to that of other flavonoids
      due to its particular structure. Nevertheless, it has low oral bioavailability,
      which limits its therapeutic application. In this context, potentially important
      approaches for systemic drug delivery could be by alternative routes such as skin
      and vaginal mucosa, once both routes have a variety of advantages compared with
      the oral route, including the ability to bypass both first-pass hepatic
      metabolism and the consequent degradation in the gastrointestinal tract. Vaginal
      delivery could also account for a local effect, or an effect on circumvent
      microregion. OBJECTIVE: The major objective of this study was to develop and
      validate a high-performance liquid chromatography (HPLC) method for the
      determination of TAX in a semisolid dosage forms and then to evaluate ex vivo
      permeations across porcine vaginal mucosa and human skin. METHODS: TAX was
      incorporated into an oil-in-water emulsion developed previously by our group.
      Method for quantification was developed and validated using HPLC. Permeation
      through human skin and vaginal porcine mucosa were conducted in Franz-type cells.
      RESULTS: The method was precise (CV < 5%), accurate (recovery between 98% and
      102%), linear (R2> 0.99), specific, and robust. Permeation experiments through
      porcine vaginal mucosa and human skin presented permeated percentages equal to
      87.43% and 48.09% (per dose), respectively. CONCLUSION: The results suggest that,
      in the matrixes studied, TAX may be able to exert its biological activities
      systemically when applied by these routes. Furthermore, it exhibits greater
      permeability potential when administered by intravaginal route.

PMID- 29336265
TI  - Efficacy of Aloe vera/ Plantago major gel in Diabetic Foot Ulcer: a randomized
      double-blind clinical trial.
AB  - BACKGROUND: Diabetic foot ulcer (DFU) is one of the most common complications of
      diabetic patients. Mostly, non-healing DFU leads to infection, gangrene,
      amputation and even death. High costs and poor healing of the wounds need a new
      treatment such as alternative medicine. So, the aim of this study was to evaluate
      the efficacy of Aloe vera/ Plantago major gel (Plantavera gel) in healing of DFU.
      METHODS: Forty patients with DFU enrolled in a double-blind randomized clinical
      trial. The patients who were randomly assigned into the intervention group (n =
      20), received topical Plantavera gel in addition to the routine cares, whereas
      the patients in the control group (n = 20), received topical Placebo gel in
      addition to the routine cares. Intervention was done twice a day for 4 weeks in
      the both groups. Photography and an evaluation of DFU healing were conducted by a
      checklist and then were scored at baseline and at the end of each week. The
      collected data was analyzed by SPSS software. RESULTS: At the end of the study,
      there was a significant difference between the two groups in terms of total ulcer
      score (P<0.001) and Plantavera gel significantly reduced the ulcer surface
      comparing with the control group (P=0.039). However, there was not a significant
      difference between the two groups (P=0.263) in terms of the ulcer depth. During
      this study, no side effect was observed for Plantavera gel in the intervention
      group. CONCLUSION: Topical Plantavera gel seems to be an effective, cheap and
      safe treatment. Of course, further studies are required to confirm the properties
      of the wound healing of this gel.

PMID- 29336266
TI  - Design, Synthesis, Evaluation and Computational Studies of Nipecotic Acid
      Acetonaphthone Hybrids as Potential Antiepileptic Agents.
AB  - BACKGROUND: Nipecotic acid is considered to be one of the most potent inhibitors
      of neuronal and glial gamma-aminobutyric acid (GABA) uptake in vitro. However,
      nipecotic acid does not readily cross the blood-brain barrier (BBB) following
      peripheral administration, owing to its hydrophilic nature. OBJECTIVE: A series
      of substituted acetonaphthones tethered nipecotic acid derivatives were designed
      and synthesized with an aim to improve the lipophilicity and the blood-brain
      barrier (BBB) permeation. METHODS: Synthesized compounds were tested in mice
      models of PTZ, pilocarpine, and DMCM induced epilepsy, in vivo. The rota-rod test
      was performed to determine the acute neurotoxicity of the potential leads (4a,
      4b, and 4i). These potential hybrids were also evaluated for their ability to
      cross the BBB by an in vitro parallel artificial membrane permeability BBB assay
      (PAMPA-BBB). The leads were subjected to in silico molecular docking and dynamics
      studies on homology modelled protein of human GABA (gamma-amino butyric acid)
      transporter 1 (GAT1) and prediction of their pharmacokinetic properties. RESULT:
      Amongst the synthesized derivatives, compounds 3a, 3b, 3i, 4a, 4b, and 4i
      exhibited increased latency of seizures against subcutaneous pentylenetetrazole
      (scPTZ) induced seizures in mice. Derivatives 4a, 4b, 4i were more effective
      compared to nipecotic acid ester counterparts 3a, 3b and 3i placing the
      importance of the presence of free carboxyl group in the centre. The findings
      revealed that 4i was comparatively more permeable (Pe= 8.89) across BBB than the
      standard tiagabine (Pe= 7.86). In silico studies proved the consensual
      interactions of compound 4i with the active binding pocket. CONCLUSION: Some
      nipecotic acid-acetonaphthone hybrids with considerable anti-epileptic activity,
      drug like properties and the ability to permeate the BBB have been successfully
      synthesized.

PMID- 29336267
TI  - Stem Cells Derived from Amniotic Fluid: A Potential Pluripotent-Like Cell Source
      for Cellular Therapy?
AB  - BACKGROUND: Regenerative medicine aims to provide therapeutic treatment for
      disease or injury, and cell-based therapy is a newer therapeutic approach
      different from conventional medicine. Ethical issues that rose by the utilisation
      of human embryonic stem cells (hESC) and the limited capacity of adult stem
      cells, however, hinder the application of these stem cells in regenerative
      medicine. Recently, isolation and characterisation of c-kit positive cells from
      human amniotic fluid, which possess intermediate characteristics between hESCs
      and adult stem cells, provided a new approach towards realising their promise for
      fetal and adult regenerative medicine. Despite the number of studies that have
      been initiated to characterize their molecular signature, research on developing
      approaches to maintain and enhance their regenerative potential is urgently
      needed and must be developed. AIM: Thus, this review is focused on understanding
      their potential uses and factors influencing their pluripotent status in vitro.
      CONCLUSION: In short, this cell source could be an ideal cellular resource for
      pluripotent cells for potential applications in allogeneic cellular replacement
      therapies, fetal tissue engineering, pharmaceutical screening, and in disease
      modelling.

PMID- 29336268
TI  - Anaplastic Lymphoma Kinase in Glioblastoma: Detection/Diagnostic Methods and
      Therapeutic Options.
AB  - BACKGROUND: Glioblastoma (GBM) is the most aggressive and common brain tumor in
      adults, currently lacking effective life-prolonging and recurrence-preventing
      therapy; median survival of GBM patients stands at only 14-16 months. Increasing
      lines of evidence indicate that Anaplastic lymphoma kinase (ALK), a druggable
      tyrosine kinase receptor over-expressed in GBM, represents a potential
      therapeutic target in this tumor. OBJECTIVE: An overview of the state of the art
      and the existing recent patents regarding potential exploitation of ALK as a
      therapeutic target and/or diagnostic/prognostic factor in GBM. METHOD: Recent
      literature and patents focusing on or including ALK pre-clinical and clinical
      research in GBM have been identified and reviewed, and are discussed according to
      their potential use. RESULTS: Numerous recent ALK-related patents were
      identified. They were reviewed/analyzed in relation to previously published
      research and categorized based on their potential in GBM: i) diagnosis/
      prognosis, ii) drug-based therapeutic targeting of ALK using a single compound or
      combination schemes and iii) therapeutic ALK targeting by other means, e.g. ALK
      vaccination. CONCLUSION: ALK targeting holds promise as a novel therapeutic
      approach in GBM, especially in combination schemes allowing multi-target therapy.
      Such schemes may incorporate detection-guided therapy and utilize next generation
      inhibitory compounds with improved central nervous system penetration. Moreover,
      identification of ALK-mediated molecular pathway(s) related to GBM
      carcinogenesis/ pathology and putative therapy resistance is of high priority and
      warrants further exploitation.

PMID- 29336269
TI  - Design, Synthesis, and Biological Evaluation of New Azole Derivatives as Potent
      Aromatase Inhibitors with Potential Effects against Breast Cancer.
AB  - PURPOSE: Some aromatase inhibitors are FDA-approved agents as first-line therapy
      in the treatment of endocrine-responsive breast cancer. In this study, we aimed
      to develop new azole derivatives with higher specificity and potency. METHODS:
      New aromatase inhibitors were designed by Molecular Operating Environment (MOE)
      software and synthesized in a one-step SN2 reaction. These compounds were
      characterized by melting point, 1H- and 13C-NMR, elemental analysis and mass
      spectra. The in-vitro and in-vivo aromatase inhibition of these compounds was
      evaluated using the Estrone ELISA assay, and by measuring the inhibition of
      androstenedione-induced uterine hypertrophy. The selectivity of aromatase
      inhibition was investigated by the inhibition of ACTH stimulation on the plasma
      concentrations of aldosterone and cortisol. RESULTS: Docking simulations showed
      that four new azole derivatives could efficiently interact with enzyme active
      sites. The in-vitro aromatase-inhibition assay showed that the compounds 1,3,5
      tris(imidazol-1-ylmethyl)benzene (3b) and 1,3-Bis(imidazole-1- ylmethyl) benzene
      (3d) effectively inhibited aromatase, with IC50 values of 0.2 nM and 6.8 nM,
      respectively; these values were similar to known aromatase inhibitor letrozole
      (IC50 0.3 nM). The in-vivo aromatase-inhibitory potency of compound 3b was
      similar to letrozole, although compound 3b acted more selectively. CONCLUSION:
      This report introduced a new compound that can be considered as a new lead for
      further investigation to explore more-potent and more-selective aromatase
      inhibitors.

PMID- 29336270
TI  - In silico Structure-based Identification of Novel Acetylcholinesterase Inhibitors
      Against Alzheimer's Disease.
AB  - OBJECTIVE AND BACKGROUND: Inhibition of acetylcholinesterase (AChE) has gained
      much importance since the discovery of the involvement of peripheral anionic site
      as an allosteric regulator of AChE. Characterized by the formation of beta
      amyloid plaques, Alzheimer's disease (AD) is currently one of the leading causes
      of death across the world. Progression in this neurodegenerative disorder causes
      deficit in the cholinergic activity that leads towards cognitive decline.
      Therapeutic interventions in AD are largely focused upon AChE inhibitors designed
      essentially to prevent the loss of cholinergic function. The multifactorial AD
      pathology calls for Multitarget-directed ligands (MTDLs) to follow up on various
      components of the disease. Considering this approach, other related AD targets
      were also selected. Structure-based virtual screening was relied upon for the
      identification of lead compounds with anti-AD effect. METHOD: Several
      chemoinformatics approaches were used in this study, reporting four multi-target
      inhibitors: MCULE-7149246649-0-1, MCULE-6730554226-0-4, MCULE-1176268617-0-6 and
      MCULE-8592892575-0-1 with high binding energies that indicate better AChE
      inhibitory activity. Additional in-silico analysis hypothesized the abundant
      presence of aromatic interactions to be pivotal for interaction of selected
      compounds to the acetyl-cholinesterase. Additionally, we presented an alternative
      approach to determine protein-ligand stability by calculating the Gibbs-free
      energy change over time. Furthermore, this allows to rank potential hits for
      further in-vitro testing. RESULTS AND CONCLUSION: With no predicted indication of
      adverse effects on humans, this study unravels four active multi-target
      inhibitors against AChE with promising affinities and good ADMET profile for the
      potential use in AD treatment.

PMID- 29336271
TI  - Anti-Inflammatory Drugs and Herbs with Special Emphasis on Herbal Medicines for
      Countering Inflammatory Diseases and Disorders - A Review.
AB  - BACKGROUND: Diseases with inflammatory etiopathology have increased in incidence
      in recent times. Drugs used for therapeutic management of such inflammatory
      diseases are relieving the ailment but at the same time also countering serious
      life threatening consequences. Moreover, they are costly and rarely available at
      all places. In this context, research and development on medicinal herbs have
      opened a new era in the prophylactic and therapeutic management of inflammatory
      diseases. OBJECTIVE: To highlight the importance of anti-inflammatory medicine
      synthetic drugs and natural herbs, their constituents, mechanism of action,
      benefits, side effects and future prospects. The overall aim is to provide better
      health services to patients regardless of their background on equality basis.
      RESULTS: Anti-inflammatory herbs have proven beneficial by combating inflammatory
      responses that lead to severe abnormality in body systems. Inflammation though a
      protective response to infection or injury and may result in pathological outcome
      when aggravated or of severe degree thus needs an early intervention for proper
      resolution. Medicinal plants or their constituents are considered beneficial due
      to the properties i.e., satisfactory potency, ease of availability, cheapness,
      less or no side effects, safer and efficient as compared to the synthetic
      counterparts. These medicinal herbs contain phytoconstituents that can prevent
      undesirable inflammatory processes and also posses anti-inflammatory activity.
      Steroids, glycosides, phenolics, flavonoids, alkaloids, polysaccharides,
      terpenoids, cannabinoids, fatty acids are common phytoconstituents present in
      these plants. Different mechanisms have been explored for the anti-inflammatory
      action of these active ingredients. They may synergize the anti-inflammatory
      pathway enzymes, factors, proteins or interfere with these in the inflammatory
      pathway like lipooxygenases, cyclooxygenases, tumor necrosis factors,
      interleukins, prostaglandin, nitric oxide, mitogenactivated protein, nuclear
      factor, etc. Considering all the above-mentioned factors, further research from
      molecular to cellular level will enable a better understanding of the mechanisms.
      Common antiinflammatory herbal plants are Curcuma longa, Zingiber officinale,
      Rosmarinus officinalis, Borago officinalis, Urtica dioica, Uncaria tomentosa,
      Vaccinium myrtillus, Olea europaea and much more. They are believed to be without
      side effects unlike the chemical counterparts or synthetic anti-inflammatory
      agents e.g. steroids, nonsteroid anti-inflammatory drugs, and immunosuppresants
      used for controlling and suppressing inflammatory crisis. A proper phytochemical,
      pharmacological and physiological evaluation will enable their safe and effective
      use in inflammatory conditions. Many of these anti-inflammatory drugs and herbal
      preparations have been patented with some under consideration. CONCLUSION:
      Natural herbs are safe, effective and better options as anti-inflammatory agents
      than synthetic ones. The phytoconstituents are as effective with the comparable
      mechanism of action as synthetic molecules. Future research should focus on
      molecular mechanisms of different beneficial applications of these herbal plants
      in various diseases. Recent patents on anti-inflammatory drugs and herbal plants
      have been covered which provide insight into the current status and future
      prospects in this field.

PMID- 29336273
TI  - Medications Are Risky Business.

PMID- 29336272
TI  - Let-7 miRNA Precursors Co-express with LIN28B in Cervical Cells.
AB  - BACKGROUND: The let-7 microRNAs (miRNAs) are frequently dysregulated in
      carcinogenic processes, including cervical cancer. LIN28 proteins regulate let-7
      biogenesis by binding to conserved sequences within the pre-miRNA structure.
      Nevertheless, recent research has shown that some let-7 miRNAs may escape LIN28
      regulation. OBJECTIVE: Correlate pre-let-7 miRNAs and LIN28B levels in cervical
      cell lines with different malignancy and HPV content. METHODS: Pre-let-7 levels
      were determined by RTqPCR. LIN28B and other let-7 targets were analyzed by
      immunoblot. In silico tools were used to correlate let-7 and LIN28B expression
      and to analyze prelet- 7 sequences and structures. RESULTS: Lin28B protein was
      detected in all tested cell lines although it was more expressed in tumor cell
      lines. High levels of pre-let-7c/f-1 and pre-miR-98 were present in almost all
      cell lines regardless malignancy and LIN28B expression. Pre-let-7g/i were mainly
      expressed in tumor cell lines, pre-let-7e and pre-let-7-a3 were absent in all
      cell lines and pre-let-7a-2 showed indistinct expression. LIN28B showed positive
      correlation with pre-let-7i/g/f-1 and pre-miR-98 in tumor cell lines, suggesting
      escape from regulation. Sequence alignment and analysis of pre-let-7 miRNAs
      showed distinctive structural features within the preE region that may influence
      the ideal pre-let-7 structuring for LIN28B interaction. Short preE-stems were
      present in pre-let-7 that may escape LIN28B regulation, but long preEstems were
      mostly associated with high-level pre-let-7 miRNAs. CONCLUSION: The observed
      differences of pre-let-7 levels in cervical cell lines may be the result of
      alternative preE structuring affecting interaction with LIN28B thus resulting in
      differential let-7 regulation.

PMID- 29336274
TI  - Controlling Diabetes: Continuous Glucose Monitoring for the Older Adult.
AB  - Obtaining and maintaining adequate blood glucose control in the older adult with
      diabetes offers unique challenges. Intensive blood glucose control can increase
      the risk of hypoglycemia, which can be particularly risky in the older adult.
      Adding and adjusting diabetes medications in elderly patients with multiple
      comorbidities and numerous other medications can also be challenging. The use of
      professional continuous glucose monitors-which are worn by the patient for up to
      two weeks and record blood sugars every 5 to 15 minutes-provides pharmacists and
      other health care professionals with valuable data for managing the care of the
      older adult with diabetes.

PMID- 29336275
TI  - Clinical Research That Matters: Designing Outcome-Based Research for Older Adults
      to Qualify for Systematic Reviews and Meta-Analyses.
AB  - Though older adults are more sensitive to the effects of medications than their
      younger counterparts, they are often excluded from manufacturer-based clinical
      studies. Practice-based research is a practical method to identify medication
      related effects in older patients. This research also highlights the role of a
      pharmacist in improving care in this population. A single study rarely has strong
      enough evidence to change geriatric practice, unless it is a large-scale,
      multisite, randomized controlled trial that specifically targets older adults. It
      is important to design studies that may be used in systematic reviews or meta
      analyses that build a stronger evidence base. Recent literature has documented a
      gap in advanced pharmacist training pertaining to research skills. In this paper,
      we hope to fill some of the educational gaps related to research in older adults.
      We define best practices when deciding on the type of study, inclusion and
      exclusion criteria, design of the intervention, how outcomes are measured, and
      how results are reported. Well-designed studies increase the pool of available
      data to further document the important role that pharmacists have in optimizing
      care of older patients.

PMID- 29336276
TI  - Streamlining the Medication Review Process by Use of a New Review Tool: CHART.
AB  - OBJECTIVE: The Carlson-Hamilton Adult Medication Review Tool (CHART) represents
      an effort to improve the approach to geriatric care by streamlining the
      medication review process and identifying potential medication issues that may be
      relevant to patient's cognitive presentation and impact clinical decision making.
      SETTING: CHART was created at a behavioral health facility. The most common
      primary diagnoses on this unit include new onset psychosis and recent mental
      status changes. PRACTICE DESCRIPTION: This facility contains 155 beds divided
      into six units. The geriatric unit has an average census of 10 patients, with an
      average length of stay of 10 to 12 days. PRACTICE INNOVATION: This site is
      working to improve geriatric patient care by simplifying and streamlining the
      medication review process. MAIN OUTCOME MEASUREMENTS: The pharmacy team evaluated
      change in medication burden and change in medication review requests. RESULTS:
      Following implementation, this facility saw both a decreased medication burden
      and an increase in medication review requests. CONCLUSION: CHART is a tool that
      allows pharmacists and student pharmacists to streamline the review of
      medications and make recommendations.

PMID- 29336277
TI  - Evaluation of Hypoglycemia and Potential Risk Factors in a Veterans Affairs
      Community Living Center.
AB  - OBJECTIVES: To describe hypoglycemic events in a Veterans Affairs (VA) community
      living center (CLC) population and to determine predictive risk factors
      associated with hypoglycemia. DESIGN: Retrospective, exploratory, observational
      chart review. SETTING: Tertiary-care VA Healthcare System CLC. PATIENTS:
      Residents residing in a VA CLC with at least one active order for insulin between
      June 1, 2009, and June 30, 2013, were evaluated over a 90-day study period. MAIN
      OUTCOME MEASURES: The primary outcome was the number of days to the first
      hypoglycemic event as described by the survival curve analysis. The secondary
      outcomes included the overall incidence of hypoglycemia, the association of
      potential risk factors on the proportion of hypoglycemic events, and the
      association of potential risk factors on the development of an additional
      hypoglycemic event. RESULTS: There was a 49% incidence of a hypoglycemic event in
      the 90-day study period with a 24% incidence within the first 7 days of resident
      admission, representing approximately half of all events that occurred. The only
      statistically significant risk factor for having a hypoglycemic event was the
      number of units of insulin/kg/day (hazard ratio = 1.008, 95% confidence interval
      1.001, 1.015; P = 0.0317) that a resident was prescribed. CONCLUSIONS: Residents
      are at increased risk for hypoglycemia within the first seven days of admission
      to a CLC. It is imperative that providers closely monitor and reevaluate
      antidiabetic regimens at this time of transition.

PMID- 29336278
TI  - Use of 2015 Beers Criteria Medications by Older Medicare Beneficiaries.
AB  - OBJECTIVE: To examine the prevalence of potentially inappropriate medications
      (PIMs) in community-dwelling Medicare beneficiaries based on the updated 2015
      American Geriatrics Society Beers criteria. DESIGN: Cross-sectional study.
      SETTING: Thirteen mobile Medicare clinics were held throughout Northern and
      Central California during the fall of 2015. PATIENTS, PARTICIPANTS:
      Noninstitutionalized Medicare beneficiaries 65 years of age and older taking one
      or more medications. INTERVENTIONS: Pharmacy students under direct supervision of
      licensed pharmacists performed medication therapy management (MTM). Drug and
      disease state data were collected and used to identify PIMs based on the 2015
      Beers criteria. MAIN OUTCOME MEASURES: Number of beneficiaries who are taking a
      PIM, have a potential drug-drug or drug-disease interaction, and common factors
      associated with receiving a PIM. RESULTS: MTM services were provided to 703
      beneficiaries 65 years of age or older taking 1 or more medications. In total,
      204 (29%) beneficiaries were taking 1 or more PIM. Drug-drug interactions were
      found in 54 beneficiaries, and 12 beneficiaries were found to have a significant
      drug-disease interaction. PIM prescribing was associated with certain chronic
      conditions (e.g., pain and insomnia). The prevalence of PIM use was significantly
      higher in women compared with men, whites compared with non-whites, and low
      income beneficiaries compared with high income. CONCLUSION: Prescribers and
      pharmacists should work in concert to minimize PIM use in older adults.
      Practitioners knowledgeable about the updated 2015 Beers criteria may monitor
      drug use more closely, hopefully minimizing potentially harmful drug and/or
      disease-state problems, and preventing avoidable health-related sequelae.

PMID- 29336279
TI  - CMS Proposes Sweeping Medicare Rule.

PMID- 29336280
TI  - Open access: Is there a predator at the door?

PMID- 29336281
TI  - Naive and effector B-cell subtypes are increased in chronic rhinosinusitis with
      polyps.
AB  - BACKGROUND: Recent studies demonstrated that B cells and their chemoattractants
      are elevated in the nasal mucosa of patients with chronic rhinosinusitis (CRS)
      with nasal polyposis (CRSwNP). However, the presence of naive B cells and of
      plasmablasts and memory B-cell subsets in the mucosa and periphery of the same
      patient with CRS is yet to be characterized. OBJECTIVE: Here we sought to
      quantify naive, plasmablasts, and memory B cells in mucosal tissue and peripheral
      blood of patients with CRSwNP, patients with CRS without nasal polyps (CRSsNP),
      and control patients. METHODS: Polyps, mucosa, and peripheral blood samples were
      prospectively collected from the patients with CRS and from the non-CRS controls.
      We used flow cytometry to distinguish among naive, plasmablast, and memory B
      cells in sinus tissue and peripheral blood. RESULTS: A total of 45 patients were
      recruited for the study. The patients with CRSwNP had significantly increased
      mucosal B-cell numbers versus the controls (3.39 +/- 4.05% versus 0.39 +/- 1.05%
      of live cells; p < 0.01, Kruskal-Wallis test), which included naive B cells (0.61
      +/- 0.94 versus 0.11 +/- 0.24% of live cells; p < 0.03, Kruskal-Wallis test),
      plasmablasts (0.06 +/- 0.26 versus 0.00 +/- 0.00% of live cells; p < 0.055,
      Kruskal-Wallis test), and memory B cells (0.62 +/- 1.26 versus 0.05 +/- 0.15% of
      live cells; p < 0.02, Kruskal-Wallis test). CONCLUSION: Our study identified
      increased frequencies of different B-cell subtypes in the mucosa of patients with
      CRSwNP but not in the peripheral blood. We also found that patients with CRSwNP
      had significantly increased B-cell subtypes compared with the patients with
      CRSsNP and the controls. These results implied a potential role for mucosal B
      cells in the ongoing inflammation in patients with CRSwNP.

PMID- 29336283
TI  - Headaches and facial pain in rhinology.
AB  - "Sinus headache" is a common chief complaint that often leads patients to an
      otolaryngologist's office. Because facial pain may or may not be sinogenic in
      origin, the otolaryngologist should be equipped to evaluate and treat or to
      appropriately refer these patients. Analysis of current data indicates that the
      majority of patients who present with sinus headaches actually have migraines.
      Furthermore, the downstream effect of the cytokine cascade initiated in migraine
      physiology can cause rhinologic symptoms, including rhinorrhea, congestion, and
      lacrimation, which may also confound diagnosis. Other causes of sinus headache
      include the following: cluster headaches, Sluder neuralgia, trigeminal neuralgia,
      myofascial trigger point pain (tension headaches, temporomandibular joint
      dysfunction), and contact point headaches. The diagnostic dilemma for an
      otolaryngologist occurs when a patient has facial pain and symptoms that may
      indicate chronic rhinosinusitis but with nondiagnostic endoscopy. Traditionally,
      these patients have been primarily managed with empiric antibiotics. An
      alternative strategy is to first screen these patients with an upfront computed
      tomography. This algorithm may ultimately decrease cost; avert unnecessary
      antibiotics prescriptions; and prompt more timely referrals to other, more
      appropriate, disciplines, such as neurology, dentistry, and/or pain management
      specialists.

PMID- 29336282
TI  - Role of group 2 innate lymphocytes in aspirin-exacerbated respiratory disease
      pathogenesis.
AB  - Aspirin-exacerbated respiratory disease (AERD) is characterized by chronic
      eosinophilic nasal polyps, asthma, and airway reactions upon cyclooxygenase (COX)
      1 inhibition. AERD is present in up to 7% of adult patients with asthma and the
      underlying pathogenesis remains largely elusive but prostaglandin D2, cysteinyl
      leukotrienes, mast cells, and type 2 cytokines are thought to contribute. A
      wealth of studies have recently implicated group 2 innate lymphoid cells (ILC2),
      a novel lineage-negative lymphocyte population that produces type 2 cytokines, in
      human allergic disease pathogenesis. Importantly, our recent work identified that
      ILC2s are recruited to the nasal mucosa of patients on AERD after COX-1 inhibitor
      administration. Here, we review the potential impact of ILC2s in the development
      and propagation of type 2 inflammation in AERD.

PMID- 29336284
TI  - Assessing the onset of allergic rhinitis by nasal cytology and immunoglobulin E
      antibody levels in children.
AB  - BACKGROUND: It is difficult to identify the onset of allergic rhinitis in infants
      because making a conclusive diagnosis can be challenging. OBJECTIVE: We used a
      combination of cell differentials in nasal swabs and immunoglobulin E (sIgE)
      antibody values to food and inhalant allergens to make the diagnosis and identify
      relevant allergens for investigation of the onset of allergic rhinitis. METHODS:
      We studied 302 children, 2 to 120 months old, who visited our clinic for
      rhinorrhea. Nasal swabs were taken from all children, and neutrophils (N),
      eosinophils (Eo), and mast cells (Mc) were identified by nasal cytology and their
      numbers were estimated. Levels of sIgE antibodies to various food and inhalant
      allergens were determined in patients with nasal Eo and Mc. RESULTS: Percentages
      of participants with Eo-Mc and Eo-Mc-N at 2-14 (n = 84), 15-24 (n = 57), 25-60 (n
      = 73), and 61-120 months of age (n = 88) were 20, 23, 58, and 65%, respectively.
      There were no significant differences between the 2-14 and 15-24, and 25-60 and
      61-120 months age groups, but there was a significant difference between the 15
      24 and 25-60 months age groups (p = 0.00013). The percentages of participants
      with sIgE antibodies to food and inhalant allergens as solitary or main allergen
      were 12%/0% at 2-14 months old, 10.5%/7% at 15-24 months old, 1.3%/42.4% at 25-60
      months old, and 0%/56.8% at 61-120 months old, respectively with a significant
      difference between 15-24 and 25-60 months old groups (p = 0.00025) for inhalant
      allergens. CONCLUSION: Allergic rhinitis associated with inhalant allergens in
      infants <15 months of age is rare, but it is tempting to postulate that symptoms
      of rhinitis in these infants may be associated with sIgE antibodies to food
      allergens. Transition of sIgE responses from food to inhalant allergens occurred
      after 15 months of age, and sIgE antibodies to inhalant allergens were
      predominant after 25 months.

PMID- 29336285
TI  - Optimal cutoff values of allergen-specific immunoglobulin E to house dust mites
      and animal dander based on skin-prick test results: Analysis in 16,209 patients
      with allergic rhinitis.
AB  - BACKGROUND: The most common tests for allergen sensitization in patients with
      allergic rhinitis are the skin-prick test (SPT) and an in vitro test to detect
      serum specific immunoglobulin E (sIgE). However, in vitro allergen test results
      were interpreted dichotomically as positive or negative at a threshold of 0.35
      kU/L of sIgE, regardless of the patient characteristics or antigen types.
      OBJECTIVE: The purpose of this study was to determine the cutoff value for sIgE
      in house-dust mites and animal dander, and to analyze differences in cutoff value
      according to age and gender. METHODS: A total of 16,209 patients with more than
      one allergic rhinitis symptom who underwent both SPT and serum sIgE testing were
      retrospectively evaluated between March 2008 and May 2012. There were 9374 male
      (57.8%) and 6835 female (42.2%) patients. The mean age was 31.8 years (range, 2
      89 years). The criterion standard for allergen sensitization was defined as a
      wheal of >3 mm or an allergen-to-histamine ratio of >=1 in SPT results. The
      Youden index was used to calculate the cutoff value of sIgE. RESULTS: Cutoff
      values of sIgE for Dermatophagoides pteronyssinus, Dermatophagoides farinae, cat,
      and dog were 0.69, 1.16, 0.13, and 0.45 kU/L, respectively. The cutoff value of
      sIgE changed according to age for D. pteronyssinus and D. farinae but not for cat
      and dog allergens. When categorizing according to age group, the cutoff values of
      sIgE for D. pteronyssinus and D. farinae had a tendency to decrease with age.
      There was no significant difference in cutoff value according to gender.
      CONCLUSION: The cutoff value for sIgE differed for each antigen and changed with
      age. Physicians should select the proper cutoff value for sIgE for appropriate
      criteria according to antigen and patient age rather than using a uniform cutoff
      value.

PMID- 29336286
TI  - Oral allergy syndrome.
AB  - OBJECTIVES: To review oral allergy syndrome (OAS). METHODS: We searched several
      medical literature data bases with the following key words: "oral allergy
      syndrome," "OAS," "pollen-food allergy syndrome," "PFAS," "allergy," "diagnosis,"
      "treatment." RESULTS: Oral allergy syndrome (OAS), also called "pollen-food
      allergy syndrome," is a type of food allergy brought about by flavors, nuts, raw
      fruit, and vegetables. The most well-known symptoms are mouth and throat itching,
      which starts rapidly after a food is placed in the mouth, and that, as a rule,
      continues for just a couple of minutes after the food has been swallowed. The
      frequency of OAS with pollen allergy has been reported as 5-8%; 1-2% of patients
      with OAS with pollen allergy show extreme responses, e.g., anaphylaxis. Birch
      tree pollen, ragweed pollen, and grass pollen hypersensitivity cause the
      symptoms. The diagnosis of OAS is confirmed by a positive history and positive
      skin-prick test result triggered by the food's fresh extract. Oral challenge
      result is normally positive with the raw food and negative with the similar
      cooked food. CONCLUSION: Patients with grass allergy may have a response to
      peaches, oranges, celery, tomatoes, and melons. Patients with ragweed allergy may
      show OAS symptoms with melon, cucumber, banana, and zucchini. Physicians should
      be aware of OAS and know the appropriate treatment.

PMID- 29336287
TI  - Endoscopically assisted Crawford tube placement results in shorter general
      anesthesia times in pediatric patients.
AB  - BACKGROUND: Crawford tube placement is commonly used to achieve patency of
      nasolacrimal ducts for epiphora secondary to nasolacrimal duct obstruction. The
      nasal passages of pediatric patients are narrower than adults, and the result is
      a relatively higher risk of intranasal complications (e.g., synechiae, bleeding)
      with Crawford tube placement. There is evidence that general anesthesia may
      negatively affect the neurocognitive function and behavioral development of
      children, which prompts efforts to decrease operation times for potential health
      benefits and also potentially to reduce health care costs. Analysis of research
      reports supports the use of nasal endoscopy to reduce intranasal complications
      with Crawford tube placement; however, no publications currently address the
      effect of nasal endoscopy concurrent with Crawford tube placement on operative
      times on pediatric patients or the resulting effects on health care costs.
      OBJECTIVE: To determine the difference in procedure time and cost between
      Crawford tubes placed traditionally and those placed with endoscopic assistance
      in pediatric patients. METHODS: A chart review was performed from January 1, 2011
      to December 31, 2016 for cases using CPT codes 68815 or 31231. Within this group
      of patients, the patient in whom nasal endoscopy was performed were placed in the
      "endoscopic" group and the patients without endoscopy were placed in the
      "traditional" group. Procedure times were noted, and the t-test was performed to
      examine for any statistically significant difference in operative times.
      Estimates of anesthesia cost savings were made. We identified 24 patients in the
      traditional group and 7 patients in the endoscopic group. RESULTS: The average
      operative time for the traditional group was 27.3 minutes compared with 14.0
      minutes for the endoscopic group (p = 0.02). The cost comparison data revealed no
      significant difference with the traditional group averaging $9369 per procedure
      and the endoscopic group averaging $8891 (p = 0.51). CONCLUSION: An
      endoscopically assisted Crawford tube placement resulted in patients who had less
      time under general anesthesia compared with the traditional technique at no
      difference in cost.

PMID- 29336288
TI  - How often is sinus surgery performed for chronic rhinosinusitis with versus
      without nasal polyps?
AB  - BACKGROUND: There currently are no data on the relative frequency of endoscopic
      sinus surgeries (ESS) performed for chronic rhinosinusitis with nasal polyposis
      (CRSwNP) versus chronic rhinosinusitis without nasal polyposis (CRSsNP) in the
      United States. OBJECTIVES: To compare the rate of surgical interventions for
      CRSwNP and CRSsNP. METHODS: Cases identified by CPT codes were extracted from the
      2009-2011 State Ambulatory Surgery Databases for California, Florida, Maryland,
      and New York. Patient demographics, extent of surgery, mean charges, and
      operating room (OR) time were compared. RESULTS: A total of 97,228 ESS cases were
      performed in the four states; 29.3% of surgeries were for patients with CRSwNP,
      66.0% of patients with CRSsNP, and 4.8% for other indications. The proportion of
      ESS for CRSwNP varied across states, with California having the highest
      percentage (34.6%) and Maryland having the lowest (26.4%) (p < 0.0001). Patients
      with Medicaid (33.8%) and Medicare (32.2%) had higher rates of surgery for CRSwNP
      compared with patients with private insurance (29.9%) (p < 0.001). Surgeons who
      performed a higher volume of sinus surgery compared to lower volume surgeons
      performed a lower percentage of surgery for CRSwNP (24.4 versus 33.5%; p <
      0.001). ESS cases for CRSwNP were more extensive (relative risk of four sinus
      surgeries of 1.88; p < 0.0001), used image guidance more frequently (relative
      risk, 1.39; p < 0.0001), and were less likely to include a balloon procedure
      (relative risk, 0.69; p < 0.0001). Patients with CRSwNP had longer OR times (ESS
      that involved all four sinuses took 14 minutes longer) (p < 0.0001), but no
      difference in charges compared with patients with CRSsNP who underwent a similar
      extent of surgery. CONCLUSION: Almost 30% of ESS were performed for CRSwNP, and
      these cases were, on average, more extensive, used more OR time, and more often
      used image guidance than surgeries for CRSsNP. The rate of surgery performed for
      CRSwNP varied based on geography, payer, and surgical volume, which indicted that
      patient selection impacted surgical management.

PMID- 29336289
TI  - Management of odontogenic cysts by endonasal endoscopic techniques: A systematic
      review and case series.
AB  - BACKGROUND: Odontogenic cysts and tumors of the maxilla may be amendable to
      management by endonasal endoscopic techniques, which may reduce the morbidity
      associated with open procedures and avoid difficult reconstruction. OBJECTIVE: To
      perform a systematic review that evaluates the feasibility and outcomes of
      endoscopic techniques in the management of different odontogenic cysts. A case
      series of our experience with these minimally invasive techniques was assembled
      for insight into the technical aspects of these procedures. METHODS: The
      Preferred Reporting Items for Systematic Reviews and Meta-Analyses was used to
      identify English-language studies that reported the use of endoscopic techniques
      in the management of odontogenic cysts. Several medical literature data bases
      were searched for all occurrences in the title or abstract of the terms
      "odontogenic" and "endoscopic" between January 1, 1950, and October 1, 2016.
      Publications were evaluated for the technique used, histopathology,
      complications, recurrences, and the follow-up period. A case series of patients
      who presented to a tertiary rhinology clinic and who underwent treatment of
      odontogenic cysts by an endoscopic technique was included. RESULTS: A systematic
      review identified 16 case reports or series that described the use of endoscopic
      techniques for the treatment of odontogenic cysts, including 45 total patients.
      Histopathologies encountered were radicular (n = 16) and dentigerous cysts (n =
      10), and keratocystic odontogenic tumor (n = 12). There were no reported
      recurrences or major complications for a mean follow-up of 29 months. A case
      series of patients in our institution identified seven patients without
      recurrence for a mean follow-up of 10 months. CONCLUSION: Endonasal endoscopic
      treatment of various odontogenic cysts are described in the literature and are
      associated with effective treatment of these lesions for an average follow-up
      period of >2 years. These techniques have the potential to reduce morbidity
      associated with the resection of these lesions, although comparative studies
      would better define specific indications.

PMID- 29336290
TI  - Comparison between endoscopic and external dacryocystorhinostomy by using the
      Lacrimal Symptom Questionnaire: A pilot study.
AB  - BACKGROUND: Epiphora has a significant impact on the patient's quality of life
      and is commonly caused by nasolacrimal duct obstruction. Dacryocystorhinostomy
      (DCR) has traditionally been performed via an external approach, which involves a
      skin incision. With the advent of endoscopes, the endonasal approach to DCR has
      gained significant popularity. METHOD: To prospectively compare the quality of
      life of adult patients who underwent either an endonasal or an external DCR for
      acquired nasolacrimal duct obstruction, the Lacrimal Symptom Questionnaire (Lac
      Q) was administered before and after surgery. The treatment group assignment was
      nonrandom and performed based on patient preference. The Lac-Q is a validated
      questionnaire that assesses the subjective perception of one's well-being from an
      eye-specific symptom and social impact standpoint. Total scores range from 0 (no
      concerns) to 33 (maximal degree of ocular symptoms and social impact). RESULTS:
      Sixty patients (22 in the endonasal group, 38 in the external group) were
      recruited between January 1, 2014, and January 1, 2016. Postoperative assessment
      was performed at 3 and 6 months. Patients who underwent external DCR reported a
      median 7.0-point improvement (interquartile range [IQR], 3.0-11.0) in total Lac-Q
      scores. A 12.0-point improvement (IQR, 10.0-18.5) was seen in the endonasal group
      (p = 0.005). The median change in the social impact score was 3.0 and 4.0 in the
      external group and the endoscopic group, respectively (p = 0.029). Changes in the
      median lacrimal symptom score were 4.0 in the external group and 8.0 in the
      endoscopic group (p = 0.014). The anatomic patency rate was lower in the external
      group (60.0%) when compared with the endonasal group (90.4%). Patients in the
      external DCR group were significantly older (median age, 51 versus 41 years).
      CONCLUSION: Our study indicated that both endonasal and external DCR can lead to
      improvement in quality of life by using a validated questionnaire. Although there
      are differences in age and anatomic success rates between the two groups,
      subgroup analyses indicated that the differences in the Lac-Q scores persisted
      when age and anatomic patency were removed as potential confounding factors.
      Further larger, randomized studies would be helpful.

PMID- 29336291
TI  - Extent of surgery in endoscopic transsphenoidal skull base approaches and the
      effects on sinonasal morbidity.
AB  - BACKGROUND: Endoscopic transsphenoidal skull base surgery (ETSS) is now
      considered the criterion standard approach for resection of pituitary adenomas
      and other midline anterior skull base lesions. Normal sinonasal structures are
      resected during ETSS, which raises concerns for nasal morbidity and patient-based
      outcome. OBJECTIVE: To perform a surgical outcome assessment by examining whether
      the extent of ETSS approaches affected patient-specific sinonasal quality of life
      as measured by the 22-item Sino-Nasal Outcome Test (SNOT-22). METHODS: A single
      center prospective cohort study of patients operated on by the same skull base
      team between 2012 and 2016. Patients with completed pre- and postoperative SNOT
      22 were included. The primary outcome was SNOT-22 scores at preoperative, 0-1
      month, 2-4 months, >5 months follow-up. Age, sex, tumor pathology, surgical
      procedure, and intraoperative cerebral spinal fluid leak repair were also
      obtained. RESULTS: Of the 249 ETSS performed, 148 patients (59%) had at least one
      completed SNOT-22; 45 (18%) met the inclusion criteria. Sinonasal quality of life
      based on SNOT-22 at the 0-1-month follow-up was significantly worse than the
      presurgical levels (p < 0.05). However, there was a return of SNOT-22 scores to
      preoperative levels at 2-4 months (p > 0.05), which was sustained at >5 months (p
      > 0.05). Factors such as the extent of ETSS, a previous nasal surgery, repair of
      an intraoperative cerebral spinal fluid leak, and the tumor pathology did not
      affect SNOT-22 scores at any follow-up intervals (p > 0.05). CONCLUSION:
      Sinonasal quality of life worsened after ETSS at 0-1 month follow-up but returned
      to preoperative levels at 2-4 months and remained at postoperative levels >5
      months. Analysis of these data will allow us to educate our patients that the
      anticipated nasal morbidity after ETSS is usually only transient and should be
      expected to recover to preoperative levels.

PMID- 29336292
TI  - Use of intraoperative negative margins reduces inverted papilloma recurrence.
AB  - BACKGROUND: Recurrence of inverted papilloma (IP) is a problem in 12-17% of
      tumors. Controversy exists regarding benefits of intraoperative frozen section
      histopathology (IFSH) for IP resection; however, to our knowledge, no study has
      specifically investigated this. IFSH for IP resection is the standard of care in
      our practice. We, therefore, reviewed our outcomes of using IFSH for IP
      resection. A secondary goal was to assess the reliability of IFSH. METHODS:
      Patients with IP who underwent surgical resection (2010-2016) with minimum 9
      month follow-up were included. RESULTS: Twenty-two adults with IP met inclusion
      criteria. All underwent surgery via endoscopic techniques, supplemented by
      external ports in five patients. At the time of presentation, 36% IPs were
      recurrent tumors; 68% were graded as Krouse stage 3. Resection was conducted
      until "clear" (negative) mucosal margins were achieved on IFSH. In 6 (27%), a
      "positive" IFSH result dictated additional resection to clear margins. Final
      negative margins were achieved in all the patients. Both positive and negative
      predictive values for IFSH were 100% (concordance with final pathology results).
      Surveillance was performed every 1-6 months with nasal endoscopy by using imaging
      when necessary. No recurrences were noted (0%) at mean follow-up of 40 months
      (range, 10-73 months). CONCLUSIONS: Positive IFSH results led to increased
      resection in 27% of the patients, with a 0% recurrence rate in this cohort. The
      reliability of IFSH for IP is very high. No recurrence of IP was noted in any
      patient at a mean follow-up of 3.3 years. IFSH may help reduce recurrence rates
      of IP, but additional studies with longer follow-up are warranted.

PMID- 29336293
TI  - Using the nasoseptal flap for reconstruction after endoscopic debridement of
      radionecrosis in nasopharyngeal carcinoma.
AB  - BACKGROUND: Radionecrosis is a complication of nasopharyngeal carcinoma (NPC)
      that is difficult to treat. Endoscopic debridement is the first-line treatment
      for radionecrosis. After debridement, however, either bone or the internal
      carotid artery is exposed and requires mucosal coverage. OBJECTIVES: This study
      sought to demonstrate the effectiveness of a nasoseptal flap (NSF) after
      endoscopic debridement of radionecrosis in the reconstruction of nasopharyngeal
      or skull base defects. METHODS: Nine patients with NPC who underwent navigation
      guided endoscopic debridement, followed by NSF reconstruction between April 2013
      and July 2016, were included. The patients' clinical features and outcomes were
      evaluated. RESULTS: All nine patients had headaches, and eight had a foul odor
      associated with their radionecrosis. One patient underwent three radiotherapy
      treatments, four had two treatments, and the remaining four had just one
      treatment. The foul odor disappeared after treatment in all the patients who had
      been affected. The headache was significantly reduced after treatment in all
      patients. The NSF detached in two patients. In one patient, NSF failed, and the
      patient experienced postoperative rupture of the internal carotid artery. In the
      seven other patients, the NSF successfully covered the resultant defects, despite
      one intraoperative internal carotid artery rupture. Only two patients required
      further debridement, whereas the others experienced complete healing after just
      one surgical procedure. The nasopharyngeal surface was healthy-appearing in eight
      patients (median follow-up, median 11 months). CONCLUSION: Reconstruction by
      using NSF after endoscopic debridement for radionecrosis of NPC allowed for
      faster healing and reduced the need for further debridement.

PMID- 29336294
TI  - Esthetic nasolabial angle according to the degree of upper lip protrusion in an
      Asian population.
AB  - BACKGROUND: The positioning of the nasal tip is as esthetically important as the
      tip projection when rhinoplasty is being considered. It is not uncommon for
      Asians to have a protruding upper lip and teeth that affect the nasolabial angle
      (NLA). This study aimed to find the preferred NLA according to the degree of
      upper lip protrusion in an Asian population. METHODS: A left-side lateral
      photograph of each participant was used for simulation of six different tip
      angles by using a photoshop program. First, the angles of the upper lip
      protrusion were changed into 10, 20, and 30 degrees  by a perpendicular line to
      the Frankfort line in each image; then, the NLAs were changed into six different
      angles (from 75 to 110 degrees ) for each of the three angles of upper lip
      protrusion for each model. Newly transformed images of nasal tips, six for the
      male model and six for the female model, were made by using presentation software
      slides and were placed in a random order. Then, 120 Korean raters were asked to
      choose the most preferred image from among the slides. RESULTS: In 10 degrees  of
      upper lip protrusion, the preferred mean +/- standard deviation (SD) NLAs for the
      male and female models were 88.7 +/- 6.4 degrees  and 92.9 +/- 6.9 degrees ,
      respectively. In 20 degrees  of upper lip protrusion, the preferred mean +/- SD
      NLAs for the male and female models were 80.9 +/- 6.9 degrees  and 83.9 +/- 5.7
      degrees , respectively. In 30 degrees  of upper lip protrusion, the preferred
      mean +/- SD NLAs for the male and female models were 78.4 +/- 5.5 degrees  and
      79.0 +/- 5.4 degrees , respectively. CONCLUSION: In an Asian population, the
      preferred NLA was changed to a more acute angle according to the degree of upper
      lip protrusion.

PMID- 29336295
TI  - Transnasal endoscopic resection of pediatric orbital cyst: "How I do it".
AB  - BACKGROUND: An orbital cystic lesion is a common orbital disease and has
      classically been approached via external incision. The introduction of endoscopic
      surgery has revolutionized the management of sinus and skull base disorders.
      Similarly, endoscopic techniques have been increasingly used to access
      intraorbital lesions with excellent outcomes, especially in pediatric patients.
      OBJECTIVE: We described, in detail, the surgical technique of the endoscopic
      approach to treat a pediatric orbital cyst. RESULTS: The cyst was completely
      resected, and the patient quickly recovered without any complication. CONCLUSION:
      The transnasal endoscopic surgical approach can be safe and effective for
      pediatric patients with orbital lesions. Use of this approach is based on the
      surgeon's experience and progressive instrumentation.

PMID- 29336296
TI  - Superior turbinate eosinophilia correlates with olfactory deficit in chronic
      rhinosinusitis patients.

PMID- 29336298
TI  - [Diagnosis of vaginal discharge].
AB  - Changes in vaginal discharge are often caused by imbalance in the vaginal
      microflora, and laboratory testing is usually of little use, as most microbes
      detected are commensals. In-office diagnosis in general practice using wet mount
      microscopy and Amsel criteria is helpful and often sufficient to ensure correct
      diagnosis and treatment. Laboratory testing of vaginal discharge should only be
      performed, if sexually transmitted disease is suspected, if there is treatment
      failure or inconclusive wet mount prior to gynaecological surgery, and in
      pregnant women with recurrent miscarriage or preterm birth.

PMID- 29336297
TI  - Add-on perampanel and aggressive behaviour in severe drug-resistant focal
      epilepsies.
AB  - This study aimed to investigate the incidence of aggressiveness in patients with
      severe drug-refractory focal epilepsy (DRE) who started perampanel (PER) as add
      on treatment, and to identify possible predisposing factors. Data on 49
      consecutive patients with severe DRE who initiated PER were retrospectively
      collected. Twelve of the 49 patients experienced aggressiveness as adverse event
      related to PER treatment, one third of them on low (2-4 mg/day) PER dosages. PER
      was discontinued in 10/12 patients because of aggressive behaviors.
      Aggressiveness could appear after several months or even more than one year of
      PER treatment. One third of patients with PER-related aggressiveness had
      intellectual disabilities and 5/12 patients took levetiracetam as a concomitant
      antiepileptic drug. Our study suggests that the occurrence of aggressive
      behaviors in patients with severe DRE is not uncommon during PER treatment and
      that it may occur after months or even years of treatment with a stable dosage,
      requiring PER discontinuation in the great majority of patients.

PMID- 29336299
TI  - [Duplication cyst as cause of ileus in a 16-year-old girl].
AB  - A 16-year-old girl was admitted to hospital with lower abdominal pain. An
      ultrasound examination suggested an ovarian cyst. A laparoscopic procedure found
      that a duplication cyst in the patient's ileum had caused mechanical ileus. The
      cyst was surgically resected through the creation of an end-to-end anastomosis,
      and pathological examination confirmed it to be a duplication cyst. Duplication
      cysts are a rare congenital disorder, especially past infancy. They are
      characterized by an epithelium of gastrointestinal origin and a lining of smooth
      muscle in their walls. The treatment is surgical resection when possible.

PMID- 29336300
TI  - [Successful treatment of acute promyelocytic leukaemia without chemotherapy and
      blood transfusion].
AB  - Untreated acute promyelocytic leukaemia (APL) is a rapidly lethal blood cancer.
      Conventional treatment consists of all-trans retinoic acid and chemotherapy.
      Standard chemo-therapy-containing treatments necessitate the use of blood
      products. This is a case report of typical APL in a 32-year-old female patient,
      who due to religious conviction refused supportive therapy with blood products. A
      treatment regimen consisting of all-trans retinoic acid and arsenic trioxide was
      successful without the use of blood transfusions.

PMID- 29336301
TI  - [Acute promyelocytic leukaemia].
AB  - Acute promyelocytic leukaemia has changed from being a highly fatal to a highly
      curable disease. Over time, key discoveries have identified the genetic and
      molecular abnormalities, which cause the disease. First choice of treatment has
      now changed from all-trans retinoic acid (ATRA) and chemotherapy to a chemo-free
      combination of arsenic trixoide and ATRA. This new regimen has shown equal
      responses and overall cure rates compared with the previous standard of care
      containing conventional chemotherapy, but with much lower toxicity. This will
      pave the way for better and easier treatment for elderly and frail patients.

PMID- 29336302
TI  - [Cyclizine is sold in Denmark as an over-the-counter drug and has serious side
      effects when overdosed].
AB  - Cyclizine is sold in Denmark as an over-the-counter drug and affects not only
      histaminergic but also muscarinergic, serotonergic and alpha-adrenergic
      receptors, with side effects such as respiratory depression and cardiac
      arrhythmias, leading to fatalities. Due to the numerous side effects, it raises
      questions concerning the status of cyclizine as an over-the-counter drug. Data of
      healthcare contacts because of cyclizine intoxication in the 2014-2016 period
      should be analyzed to further illuminate the health risk of cyclizine poisoning.

PMID- 29336304
TI  - Why do women with melanoma do better than men?
AB  - Harnessing female sex hormones may improve how all patients with melanoma respond
      to treatment.

PMID- 29336303
TI  - Keratinocytes mediate innocuous and noxious touch via ATP-P2X4 signaling.
AB  - The first point of our body's contact with tactile stimuli (innocuous and
      noxious) is the epidermis, the outermost layer of skin that is largely composed
      of keratinocytes. Here, we sought to define the role that keratinocytes play in
      touch sensation in vivo and ex vivo. We show that optogenetic inhibition of
      keratinocytes decreases behavioral and cellular mechanosensitivity. These
      processes are inherently mediated by ATP signaling, as demonstrated by
      complementary cutaneous ATP release and degradation experiments. Specific
      deletion of P2X4 receptors in sensory neurons markedly decreases behavioral and
      primary afferent mechanical sensitivity, thus positioning keratinocyte-released
      ATP to sensory neuron P2X4 signaling as a critical component of baseline
      mammalian tactile sensation. These experiments lay a vital foundation for
      subsequent studies into the dysfunctional signaling that occurs in cutaneous pain
      and itch disorders, and ultimately, the development of novel topical therapeutics
      for these conditions.

PMID- 29336305
TI  - Inferring joint sequence-structural determinants of protein functional
      specificity.
AB  - Residues responsible for allostery, cooperativity, and other subtle but
      functionally important interactions remain difficult to detect. To aid such
      detection, we employ statistical inference based on the assumption that residues
      distinguishing a protein subgroup from evolutionarily divergent subgroups often
      constitute an interacting functional network. We identify such networks with the
      aid of two measures of statistical significance. One measure aids identification
      of divergent subgroups based on distinguishing residue patterns. For each
      subgroup, a second measure identifies structural interactions involving pattern
      residues. Such interactions are derived either from atomic coordinates or from
      Direct Coupling Analysis scores, used as surrogates for structural distances.
      Applying this approach to N-acetyltransferases, P-loop GTPases, RNA helicases,
      synaptojanin-superfamily phosphatases and nucleases, and thymine/uracil DNA
      glycosylases yielded results congruent with biochemical understanding of these
      proteins, and also revealed striking sequence-structural features overlooked by
      other methods. These and similar analyses can aid the design of drugs targeting
      allosteric sites.

PMID- 29336308
TI  - Clinical significance of concordance or discordance between fractional flow
      reserve and coronary flow reserve for coronary physiological indices,
      microvascular resistance, and prognosis after elective percutaneous coronary
      intervention.
AB  - AIMS: We aimed to investigate the impact of concordance or discordance of
      fractional flow reserve (FFR) and coronary flow reserve (CFR) on coronary flow
      profiles and microvascular resistance after percutaneous coronary intervention
      (PCI), and the prognostic impact of the periprocedural physiological indices.
      METHODS AND RESULTS: A total of 249 de novo physiologically significant coronary
      lesions from 231 patients who underwent FFR, CFR, and index of microcirculatory
      resistance (IMR) examinations before and after PCI were included. Baseline
      characteristics and physiological indices were compared between the concordant
      (FFR <=0.80 and CFR <2.0, n=114) and discordant (FFR <=0.80 and CFR >=2.0, n=135)
      groups. Follow-up data were collected to determine predictors of cardiac events.
      Shortening of the mean transit time, CFR improvement, and decrease in the
      hyperaemic IMR were all significantly greater in the concordant territories. Cox
      proportional hazards analysis showed that a lower pre-PCI CFR was an independent
      predictor of adverse events at a median follow-up of 26.5 months, whereas neither
      the pre- nor post-PCI FFR was predictive of events. Event-free survival was
      significantly worse in patients with a lower pre-PCI CFR. CONCLUSIONS: FFR/CFR
      concordantly abnormal territories provide a favourable benefit as assessed by
      coronary physiological indices after elective PCI. The pre-PCI CFR may predict
      adverse cardiac events.

PMID- 29336309
TI  - Dedicated bifurcated balloon for coronary bifurcation lesions: a preclinical
      proof of concept.

PMID- 29336307
TI  - Activation of G protein-coupled estrogen receptor signaling inhibits melanoma and
      improves response to immune checkpoint blockade.
AB  - Female sex and history of prior pregnancies are associated with favorable
      melanoma outcomes. Here, we show that much of the melanoma protective effect
      likely results from estrogen signaling through the G protein-coupled estrogen
      receptor (GPER) on melanocytes. Selective GPER activation in primary melanocytes
      and melanoma cells induced long-term changes that maintained a more
      differentiated cell state as defined by increased expression of well-established
      melanocyte differentiation antigens, increased pigment production, decreased
      proliferative capacity, and decreased expression of the oncodriver and stem cell
      marker c-Myc. GPER signaling also rendered melanoma cells more vulnerable to
      immunotherapy. Systemically delivered GPER agonist was well tolerated, and
      cooperated with immune checkpoint blockade in melanoma-bearing mice to
      dramatically extend survival, with up to half of mice clearing their tumor.
      Complete responses were associated with immune memory that protected against
      tumor rechallenge. GPER may be a useful, pharmacologically accessible target for
      melanoma.

PMID- 29336306
TI  - MERS-CoV spillover at the camel-human interface.
AB  - Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic virus from
      camels causing significant mortality and morbidity in humans in the Arabian
      Peninsula. The epidemiology of the virus remains poorly understood, and while
      case-based and seroepidemiological studies have been employed extensively
      throughout the epidemic, viral sequence data have not been utilised to their full
      potential. Here, we use existing MERS-CoV sequence data to explore its
      phylodynamics in two of its known major hosts, humans and camels. We employ
      structured coalescent models to show that long-term MERS-CoV evolution occurs
      exclusively in camels, whereas humans act as a transient, and ultimately terminal
      host. By analysing the distribution of human outbreak cluster sizes and zoonotic
      introduction times, we show that human outbreaks in the Arabian peninsula are
      driven by seasonally varying zoonotic transfer of viruses from camels. Without
      heretofore unseen evolution of host tropism, MERS-CoV is unlikely to become
      endemic in humans.

PMID- 29336310
TI  - Two-year outcomes of high bleeding risk patients with acute coronary syndrome
      after Biolimus A9 polymer-free drug-coated stents: a LEADERS FREE substudy.

PMID- 29336311
TI  - Comparison of the effects of P2Y12 receptor antagonists on platelet function and
      clinical outcomes in patients undergoing Primary PCI: A substudy of the HEAT-PPCI
      trial.
AB  - AIMS: The HEAT-PPCI trial compared bivalirudin and unfractionated heparin in
      patients undergoing primary percutaneous coronary intervention (PPCI). The aim of
      this study was to report pre-specified, secondary analyses comparing the effects
      of P2Y12 inhibiting agents on platelet reactivity and clinical events. METHODS
      AND RESULTS: All patients received preprocedural oral antiplatelet therapy.
      During the early stages of the trial, the P2Y12 inhibitor of choice was prasugrel
      with some use of clopidogrel. Later, routine therapy switched to ticagrelor. For
      cases performed during working hours, multiple electrode aggregometry (MEA) was
      used to assess ADP-induced platelet aggregation at the end of the index
      procedure. The effect of P2Y12 inhibitors on the primary efficacy (major adverse
      cardiac events [MACE]) and safety (major bleeding) outcomes was assessed in all
      patients. Multiple logistic regression was used to adjust for differences in
      baseline characteristics. With MEA data from 469 patients, prasugrel therapy
      resulted in significantly greater suppression of ADP-induced platelet aggregation
      at 40 U (23, 78) (median; interquartile range [IQR]) when compared against
      ticagrelor 75 U (41, 100.75); p<0.001 or clopidogrel 79 U (56, 96); p<0.001. In
      the entire study population (N=1,803), prasugrel therapy was associated with
      significantly fewer MACE (26/497; 5.2%) in comparison to ticagrelor (83/1,123;
      7.4%) or clopidogrel (18/183; 9.8%); odds ratio (OR) 0.64, confidence interval
      (CI): 0.41-0.99, p=0.045. For major bleeding, there were no significant
      differences among the three groups - clopidogrel (3/183; 1.6%), prasugrel
      (13/497; 2.6%) and ticagrelor (43/1,123; 3.8%); OR 0.73, CI: 0.39-1.35, p=0.31.
      Patients treated with clopidogrel had more high-risk features and clopidogrel use
      was more common as an alternative to prasugrel. After adjustment, there were no
      significant differences in the rates of MACE (OR 0.70, CI: 0.41-1.21, p=0.20) or
      major bleeding (OR 0.80, CI: 0.41-1.60, p=0.53). CONCLUSIONS: In HEAT-PPCI,
      patients who received prasugrel (rather than clopidogrel or ticagrelor) had
      significantly greater suppression of ADP-induced platelet aggregation at the end
      of the procedure. After adjustment for differences in baseline characteristics,
      there were no significant differences in ischaemic or bleeding outcomes among the
      antiplatelet therapies.

PMID- 29336312
TI  - Apocrine mixed tumour on the abdomen: an atypical location.

PMID- 29336313
TI  - Reduced IgG anti-desmocollin autoantibody titre and concomitant improvement in a
      patient with pemphigus vegetans.

PMID- 29336314
TI  - Two cases of annular acute generalized exanthematous pustulosis induced by
      terbinafine.

PMID- 29336316
TI  - Mycosis fungoides in patients with psoriasis: an ongoing issue.

PMID- 29336315
TI  - A high neutrophil to lymphocyte ratio prior to BRAF inhibitor treatment is a
      predictor of poor progression-free survival in patients with metastatic melanoma.
AB  - Some studies have shown that a high neutrophil/lymphocyte ratio (NLR) >=4 before
      initiating ipilimumab treatment is an independent prognostic indicator of poor
      survival in patients with metastatic melanoma (MM). To determine whether the NLR
      before starting BRAF inhibitor (BRAFi) treatment in patients with (MM) is
      associated with progression-free survival (PFS). This retrospective study
      included 49 patients consecutively receiving BRAFi for MM between July 2012 and
      December 2014. Cox proportional hazards regression was used to analyse the
      relationship between NLR and other factors, such as lactate dehydrogenase (LDH),
      performance status, BRAFi as first- or second-line therapy, and corticosteroid
      intake with PFS. The NLR before starting BRAFi was significantly associated with
      PFS based on univariate analysis and multivariate analysis adjusted for potential
      confounding factors, such as LDH activity, ulceration, performance status, first
      line therapy, and corticosteroid intake. A high NLR (continuous variable) was
      associated with short PFS (HR: 1.35; 95% CI: 1.07-1.70; p = 0.01), and NLR >=4
      was associated with shorter PFS (HR: 3.24; 95% CI: 1.30-8.12; p = 0.01).
      Corticosteroid intake was not associated with short PFS based on multivariate
      analysis. An NLR >4, before starting BRAFi treatment, is an independent
      prognostic indicator of poor progression-free survival.

PMID- 29336317
TI  - Association between Helicobacter pylori infection and vulvar lichen sclerosus: a
      clinical comparative study.

PMID- 29336318
TI  - Nevus anelasticus in a school-aged girl: ultrastructural observation and Er:YAG
      laser treatment.

PMID- 29336319
TI  - Acute renal injury induced by oral valacyclovir.

PMID- 29336320
TI  - Two childhood cases of pigmented dermatofibrosarcoma protuberans with atrophic
      change.

PMID- 29336321
TI  - Epstein Barr virus and invasive mammary carcinomas: EBNA, EBERs and molecular
      profile in a population of West Algeria.
AB  - Breast cancer is the common malignancy that affects women worldwide, but
      conventional risk factors account for only a small proportion of these cases. A
      possible viral etiology for breast cancer has been proposed and Epstein-Barr
      virus (EBV) is a widely studied candidate virus. The objective of this study is
      to determine the association of EBV infection with infiltrating ductal carcinomas
      (IDC). This descriptive study was carried out in the laboratory of developmental
      biology and differentiation, from 2012 to 2014. Of 39 cases, we determined the
      clinicopathological characteristics of the population. Of the 23 cases of IDC, we
      implemented the techniques Elisa, immunohistochemistry and in situ hybridization.
      To determine the serological profile, overexpression of onco-proteins EBNA-1,
      HER2, the mitotic index Ki67 and detection of the presence of the viral genome.
      The mean age is 57.40+/-4, SBR II predominates with 70%, pN+ (27%), RE+ (58%),
      RP+ (52%), HER2 (81%), Luminal A (34%), Luminal B (14%), HER2 (24%), and triple
      negative (28%). The serological profile of IgG VCA + in IgG EBNA-1 (87%), EBNA-1
      P79 (82%) with a positive relationship between the IgG EBNA-1 and EBNA-1 P79
      serology profile (p=0.001), HER2 (p=0.003) and with the molecular profile
      (p=0.051), EBNA-1 overexpression in (13%). The viral genome (EBER) is found in
      the tumors 43% representing an inverse relationship with the overexpression of
      Ki67 and a positive relationship with the overexpression of HER2. In our study we
      found an association with the presence of the EBV virus and the IDC studied.

PMID- 29336322
TI  - Treatment of nail psoriasis with topical application of clobetasol propionate
      0.05% solution: a pilot study.

PMID- 29336323
TI  - Nivolumab for recurrent cutaneous squamous cell carcinoma: three cases.
AB  - Programmed cell death ligand 1 (PD-L1) is frequently expressed in cutaneous
      squamous cell cancer (CSCC) and preliminary data from an ongoing clinical trial
      suggest that programmed death receptor 1 (PD-1) checkpoint inhibitors may be
      useful to treat patients with metastatic non-melanoma skin cancer. To report a
      series of three patients with advanced CSCC treated with nivolumab, showing that
      commercially available PD-1 checkpoint inhibitors may be useful in non-melanoma
      skin cancer patients without access to a clinical trial. All patients had
      previous chemotherapy. All cancers were PD-1 ligand (PD-L1)-positive based on
      immunohistochemistry. Patients consented to off-label therapy with nivolumab,
      which is commercially available in Switzerland. Two patients had a partial tumour
      response, and have been receiving therapy for more than 12 months. One patient
      had stable disease after three months, and therapy is also ongoing. So far, no
      severe adverse effects have occurred. Our cases confirm previous reports
      demonstrating a clinical effect and tolerability of PD-1 checkpoint inhibitors
      for heavily pre-treated patients with metastatic CSCC. Commercially available PD
      1 checkpoint inhibitors may be useful in these patients who should be considered
      for PD-1 checkpoint inhibitor therapy, preferentially within clinical trials.

PMID- 29336324
TI  - Diagnostic value of autoantibody titres in patients with bullous pemphigoid.
AB  - BACKGROUND: Bullous pemphigoid (BP) is the most common autoimmune blistering
      disease of the skin requiring skin and serum tests for a precise diagnosis.
      OBJECTIVES: We analysed the sensitivity and specificity of BP-relevant parameters
      and the value of autoantibody titres during follow-up of BP patients. MATERIALS &
      METHODS: In a retrospective single-centre study, we included 200 consecutive
      patients with BP and 400 non-BP patients, and evaluated the test results of
      patients' serum and skin. In addition, we followed patients' autoantibody titres
      and clinical characteristics. RESULTS: BP180-ELISA revealed the highest
      sensitivity (85.0%; specificity: 93.9%), while BP230-ELISA demonstrated the
      lowest sensitivity (55.5%; specificity: 92.9%). Direct and indirect
      immunofluorescence showed comparable results for sensitivity (77.2%/72.7%) and
      specificity (94.9%/93.7%). The sensitivity for skin histology was 76.3%
      (specificity: 81.3%). Longitudinal analysis showed significant changes in
      autoantibody titres. CONCLUSIONS: BP diagnostics should include serum tests for
      BP autoantibodies and skin immunofluorescence. Skin histology is supportive for
      diagnosis. Autoantibody titres are markers for disease activity.

PMID- 29336325
TI  - [Surgical and academic education in Urology.]

PMID- 29336326
TI  - [Current status of Urological Education in Spain.]
AB  - INTRODUCTION: Urology is a medicalsurgical specialty that deals with the study,
      diagnosis and treatment of medical and surgical conditions of the urinary tract
      and retroperitoneum in both sexes and of the male genital tract without age
      limit. The traditional method of training is based on the imitation of the skills
      and behaviors of the tutors, creating variability in the training between
      different centers and giving a passive role to resident internal physicians
      (MIR). LEGISLATIVE FRAMEWORK: The 2006 BOE establishes the specific formative
      content in its theoretical, practical and scientific facets. At the beginning of
      the MIR training period, the first year focuses on general surgical training and
      the remaining four on specific urological training. The current legislative
      framework that regulates our specialty is one of the oldest, with no prospect of
      renewal, since this would be carried out with the development of the trunk
      project, currently paralyzed after the judgment of the Supreme Court. Therefore,
      we are in a situation of uncertainty with a legal framework in renewal plans.
      CURRENT STATE OF TRAINING: a National survey shows the degree of surgical
      participation of the MIR is low, as well as training on models and course
      attendance. In addition, the self-confidence they feel for interventions that
      could be considered of low complexity is high, for activities such as
      consultation is moderate and for interventions of moderate-high complexity is
      low. CONCLUSION: The current training program is upgradeable. New studies and
      efforts should aim to standardize the acquisition of surgical and non-surgical
      skills, guarantee access to surgical training courses, establish a minimum of
      required interventions per year and at the end of residency, foster academic
      training, participation in research of residents and achieve an objective
      assessment of the specialty.

PMID- 29336327
TI  - Current status of urological training in Europe.
AB  - Modern urological training has changed drastically in the past years, due to the
      global surgical training trends, advances in technology, subspecialization of the
      field and, working hour regulations for doctors. The lack of a standardized
      curriculum across Europe, puts in evidence the great difference in the
      requirements in every country, from the start of the residency, to obtaining the
      accreditation. We sought to identify problems related to medical, scientific and
      surgical activity during urological training, and summarize data obtained from
      surveys realized during the European Urology Residents Education Programme
      (EUREP) in 2013, and from countries such as Germany, Italy and Spain. Data from
      surveys reveals an evident lack of surgical confidence across all participants
      for major procedures, a general non-compliance with the working hour regulations,
      and a worrisome risk for burnout and negative consequences in resident's personal
      lives. Possible solutions are discussed, involving an early preference for a
      particular practice, and a standardized simulation-based training. The European
      Association of Urology (EAU) and the European School of Urology (ESU) offer a
      wide range of working groups, educational and scientific activities for improving
      the acquisition of competencies (surgical and scientific) of residents and
      urologists at any point of their career. We describe a brief description of the
      most important EAU and ESU opportunities.

PMID- 29336328
TI  - Needs, realities and expectations for urology training: Questionaire-based study.
AB  - OBJECTIVE: Urology residency training is a difficult and complex education period
      for urology residents. This education period differs in countries and mainly for
      5 years. In this study, we aimed to assess the expectations and the realities for
      Turkish urology residents and to evaluate the adequacy of their education in the
      field of urology. METHODS: In this study, 113 Turkish urology residents have been
      included and residents were asked 24 questions related with their surgical
      skills, thoughts towards their educations, their future plans and including
      demographic information. RESULTS: The years of residency were divided as; 1st
      year-12 (10.6%), 2nd year-17 (15%), 3rd year-22 (19.4%), 4th year-24 (21.3%) and
      5th year-38 (33.7%). Mainly they suffered from the lack of practical education
      and the lack of encouragement to scientific and academic works, studies.
      CONCLUSION: Urological education must be standardized and must cover the
      educational needs of urology residents.

PMID- 29336329
TI  - [Current status of urological training in Latin America.]
AB  - OBJECTIVE: Achieving residents' medical training of quality is a constant concern
      in the Confederacion Americana de Urologia (CAU), the third Urological Society
      worldwide. We aim to analyze the diversity of state training programs, with the
      intention to identify opportunities for global improvement within them and also
      to analyse the professional reality in different countries. METHODS: Data from
      2nd and 3rd Foro Educativo CAU regarding postgraduate training and labour
      implications are reviewed. This information is complemented by the opinion of
      representatives involved with the academic training in Confederacion Americana de
      Urologia, who have analyzed the reality and current status of the urological
      training through a 10-question survey that describes different aspects of
      residency program in the countries confederated in CAU. RESULTS: A total of 3,000
      graduate doctors train as residents in Urology at the CAU environment. Each year
      670 residents begin their training program in Latin America, Spain and Portugal,
      a territory that serves nearly 650 million people, with an active professional
      force of around 16.800 professionals. Detailed data on training, employment and
      supporting reality in the countries that comprise the CAU are presented. We also
      discuss the proportion of residents who carry out research and doctorate during
      the residency program. Finally, we examine the proportion of professionals who
      receive specific training at the end of their residence, the relative importance
      of this training and what are the most popular environments to carry it out.
      CONCLUSIONS: Current postgraduate training in CAU environment is heterogeneous in
      their programs, as well as in the modes of accreditation and recertification.
      Academic activities do not seem to be properly valued. However, specific training
      offers better expectations of professional development.

PMID- 29336330
TI  - [The current urological training program in Spain. Urology National Specialty
      Commission.]
AB  - OBJECTIVES: 44/2003 Law involved the creation of the National Council of
      Specialties in Health Sciences and the National Commissions of the Specialties in
      Health Sciences. METHODS: Analysis of the main laws implicated in Specialized
      Training and the role of the National Specialty Commission. DISCUSSION: 44/2003
      Law regulates the training of health professionals and establishes the procedure
      for the training programs creation by the National Specialty Commission and its
      later approval and publication in the BOE. Access to specialized training will be
      carried out with the annual and national MIR exam. The Health Ministry
      establishes the criteria for educational centers accreditation, and the National
      Specialty Commission issues a favorable or unfavorable report as advisor about
      new accreditation requests. 183/2008 RD develops the tutor figure, the formative
      evaluation through the Resident's Book and how will be like the external
      rotations. CONCLUSIONS: to understand the Urology's specialty training system we
      must know the laws that regulate it, being the most important the 44/2003 Law.
      The National Specialty Commission is an advisory party of the Ministry, whose
      main function is to elaborate the Urology training program and to establish the
      evaluation criteria of the specialists in formation.

PMID- 29336331
TI  - [Job status after the resident training period in Spain. Analysis of a national
      survey.]
AB  - OBJECTIVES: Since the establishment of specialization of medicine through the
      residency system, Spanish health care has sought to maintain a balance between
      established needs and trained professionals, with the aim of avoiding the deficit
      or excess of health specialists with its consequences. The objective of the
      present review is to know the working conditions of urologist specialists at the
      end of the residency training period. METHODS: The results of a survey for
      urologist who completed their residency contract from 2012 to 2016 are presented,
      assessing working status, academic and working data during the first months after
      the completion of specialized training. RESULTS: A total of 42 surveys were
      collected. All respondents had a working contract within 6 months of completing
      their training. 71% had a temporary contract, most with duration of less than one
      year. There are more contract numbers in the public health system, although they
      increase progressively in the private sector. More than half of the respondents
      were satisfied with their work situation. CONCLUSIONS: The work insertion of the
      recently specialized urologists is high, reaching 100% within 6 months of
      finishing their specialization. Labor quality issues are not so positive,
      observing great working instability associated to a high proportion of temporary
      contracts lower than 6 months.

PMID- 29336332
TI  - [Fatigue syndrome: Stress, Burnout and depression in Urology.]
AB  - OBJECTIVE: To determine the factors related to stress, Burnout and depression in
      urology, as well as consequences in residents and urologists, in addition to the
      possible applicable strategies to diminish and treat them. ACQUISITION OF THE
      EVIDENCE: Depression, stress and Burnout syndrome has become a problem in urology
      specialty. These topics have gained interest in international congresses and
      urological associations. Efforts are being made to find related factors as well
      as possible strategies and applicable support programs. SYNTHESIS OF EVIDENCE:
      Burnout frequency is higher among health professionals than general population,
      40-76% in students and residents, its incidence has skyrocketed in recent years,
      in addition Urology is one of the specialties with highest incidence and
      severity. Its increase has been related to work overload, documentation,
      administrative/bureaucratic workload, hostile work environment; its consequences
      include poor work performance, medical errors, depression, substance abuse,
      disruption in family and couple relationships and suicidal ideation. Strategies
      for prevention including resilience training, lifestyle balance, teamwork, and
      support programs. CONCLUSION: Stress, burnout and depression are problems in
      urology, early detection, promoting individual techniques in resilience,
      lifestyle and teamwork are fundamental now and for the future of the specialty.
      Developing and implementing support programs should be seriously considered by
      health systems and urological associations.

PMID- 29336333
TI  - Simulation and training in Urology - in collaboration with ESU/ESUT.
AB  - Being a Surgeon today means taking on your shoulders countless responsibilities.
      It is definitely a high-stakes job but, even though the professionals do not go
      through the intense, focused and demanding training schedule as followed by the
      other equally risky fields, it doesn't yet require any practical training
      certification. Simulation was introduced in the aviation field in the early '30s
      with the "Link Trainer", designed to reproduce the most difficult flying case
      scenario: landing on an air-carrier. After almost a century, flight simulation is
      still becoming more sophisticated, while surgical training is slowly starting to
      fill the gap. The aim of a simulator is to produce an "imitation of the operation
      of a real-world process or system over time". This short but effective definition
      explains why simulators are utilised across different fields. There is no doubt
      that surgeons are continuously undergoing a condition of stress, even in
      nonthreatening situations, while performing a procedure. This condition adds a
      relevant variable to surgery, meaning that mastering technical skills is not
      always equal to "safe surgery". This is why "non-technical skills" (NTS) training
      should be a part of any simulation based training opportunity and will probably
      start to be always more part of the Handson Training programs.

PMID- 29336334
TI  - [Training in basic and advanced laparoscopy: Evaluation of a 30-year experience
      in a training program in Spain.]
AB  - The lack of globally established standards for learning urological laparoscopy
      has not prevented laparoscopic techniques from evolution and continuous
      development. Laparoscopy coexists with robotic surgery today, and in the last
      decade there have been many techniques that have undergone a boom with the use of
      a laparoscopic approach (total and partial nephrectomy, pyeloplasty,
      colposacropexy, etc.).We intend to evaluate the progressive incorporation of
      different surgical techniques in the laparoscopic learning program and, on the
      other hand, to analyze the evolution of training programs in urological
      laparoscopy to bring this type of techniques within the hospital surgical
      activity. We describe our 30-years experience in different training programs in
      urological laparoscopy that have been sponsored by the Spanish Association of
      Urology (AEU), and have undergone several validity studies to assess their
      capacity in order to evaluate effectively basic and advanced laparoscopic skills.
      We will also highlight the current and future trend towards training models based
      on surgical competences where individualized training, accreditation and
      specialization of tutors is crucial, and where the increase in the use of
      training and evaluation methods based on the simulation are increasingly common.

PMID- 29336335
TI  - [Evaluation of competencies in urology. Esscolap(r) basic, as aproximation to
      urologists skills improvement.]
AB  - : Urology needs models of competencies assessment, although there is a wide range
      of tools not yet integrated into the official training programs. CONTEXT: At
      present, there is no universal framework for measuring surgeons' level of
      competence. Urology training programs should provide and consider knowledge,
      pyschomotor/cognitive skills, and simulator, cadaver or animal models-based
      training. Validity is a complex concept that refers to the capacity of the
      evaluation tool, so it is necessary to demonstrate several types of validation to
      assure the capacity of a method, reinforced with different reliability tests and
      calculation of internal consistency between evaluators. OBJECTIVE: Based on a
      structured dossier of surgical skills, classified by groups, the ESSCOLAP(r)
      Basic system was proposed with 5 simulator tasks to evaluate basic laparoscopic
      skills. Once validated in the JUMISC (Spain), the tool was proposed to extend its
      scope and implementation in other locations. RESULTS: Our system has not yet
      demonstrated a full validity in the real clinical setting because a predictive
      validity needs to be demonstrated on the basis of clinical data. It also suffers
      from a certain range of subjectivity, thus implying clear and defined criteria
      for any situation. Factors like the number of evaluators and tasks to assess will
      influence the reliability tests that measure the degree of agreement between
      evaluators, so that a higher number of evaluated cases would imply a greater
      reliability of our system. Finally, we assume that the incorporation of this type
      of tools implies an added cost, charged to the public and private responsible
      institutions, which will only be considered cost-effective when it is
      demonstrated its real and positive traceability in health outcomes. CONCLUSIONS:
      ESSCOLAP(r) Basic, of quick and simple implementation capacity, has been
      validated and calibrated for the evaluation of basic technical skills in
      laparoscopy.

PMID- 29336336
TI  - [Training program in urological laparoscopic surgery. Future perspective.]
AB  - Nowadays in urology, laparoscopic surgery is a reality that implies a very high
      percentage of the daily surgical activity. The interest in laparoscopy in
      urological pathology is undeniable, and the advantages for our patients with this
      approach are clear in most cases. But how do we deal with learning curve of this
      technique? What is the difficulty in laparoscopy training? What future
      perspectives might offer this approach? Difficulties in learning laparoscopy are
      easily identified and clear. The loss of the image in 3 dimensions, loss of
      touch, great dependence on surgical instruments, among others. For all these
      reasons, it seems common sense that the learning of laparoscopic surgery is
      structured and organized in a progressive increase in the difficulty of the
      exercises, which will seek to acquire the necessary skills before facing the
      patient inside the operating room.

PMID- 29336337
TI  - [Training program in endourological surgery. Future perspectives.]
AB  - Current training in urological endoscopy lacks a specific training program.
      However, there is a clear need for a specific and uniform program, which will
      ensure the training, regardless of the unit where it is carried out. So, the goal
      is to first evaluate the current model and then bring improvements for update.
      The hospital training accreditation programme are only the adjustment of the
      official program of the urology specialty to the specific circumstances of each
      center, which causes variability in training of residents. After reviewing 19
      training programs belonging to 12 Spanish regions. The current outlook shows that
      scarcely 10% of hospitals quantify the number of procedures/ year, although the
      Spanish program emphasizes that the achievement of the residents should be
      quantified. Urology residents, sense their training as inadequate and therefore
      their level of satisfaction is moderate. The three main problems detected by
      residents as an obstacle on their training are: the lack of supervision, tutors
      completing their own learning. Finally, the lack of quantification in surgical
      activities is described as a threat. This has no easy solution, since the
      learning curve of the most common techniques in endourology is not correctly
      established. Regarding aspects that can improve the current model, they highlight
      the need to design a specific program. The need to customize the training, the
      ineludible accreditation of tutors and obviously dignify the tutor's teaching
      activity. Another basic aspect is the inclusion of new technologies as training
      tools, e-learning. As well as the implementation of an adequate competency
      assessment plan and the possibility of relying on simulation systems. Finally,
      they highlight the need to attend monographic meetings and external clinic
      rotations to promote critical training.

PMID- 29336338
TI  - Training in urological robotic surgery. Future perspectives.
AB  - As robotics are becoming more integrated into the medical field, robotic training
      is becoming more crucial in order to overcome the lack of experienced robotic
      surgeons. However, there are several obstacles facing the development of robotic
      training programs like the high cost of training and the increased operative time
      during the initial period of the learning curve, which, in turn increase the
      operative cost. Robotic-assisted laparoscopic prostatectomy is the most commonly
      performed robotic surgery. Moreover, robotic surgery is becoming more popular
      among urologic oncologists and pediatric urologists. The need for a standardized
      and validated robotic training curriculum was growing along with the increased
      number of urologic centers and institutes adopting the robotic technology.
      Robotic training includes proctorship, mentorship or fellowship, telementoring,
      simulators and video training. In this chapter, we are going to discuss the
      different training methods, how to evaluate robotic skills, the available robotic
      training curriculum, and the future perspectives.

PMID- 29336339
TI  - [Training program in oncologic urology. Future prospectives.]
AB  - Urology is a medical-surgical specialty that deals with the study, diagnosis and
      treatment of the medical and surgical diseases of the urinary apparatus and
      retroperitoneum in both sexes and the male genital apparatus without age limit,
      due to congenital, traumatic, septic, metabolic, obstructive and oncological
      conditions. Urologic oncology is the broadest urological part, where research and
      new advances make continuous learning essential. In this chapter we treat all
      academic features related with training in the field of Urooncology.

PMID- 29336340
TI  - [Training program on medical urology: Future perspectives.]
AB  - Urology is defined as the medical-surgical specialty that includes the study,
      diagnosis and treatment of medical conditions of the urinary system. It is well
      specified by the National Commission of Specialties that we must know the medical
      pathology that concerns us. However, on occasions, resident training focuses on
      the surgical field and oncological pathology, which, although one of the main
      pillars of the specialty, is usually to the detriment of training in medical and
      functional pathology. We conducted a survey of residents in the fourth year of
      Urology in Spain, where we asked about the quality of training in Andrology and
      Functional Urology. The average rotation time is 3.5 months in each unit. Only
      20% consider that their training is satisfactory and sufficient in Andrology.
      Seventy-five percent of residents surveyed believe that their training in
      Functional Urology is acceptable or sufficient, both medical and surgical. There
      are numerous fields of action to improve the training of residents and young
      urologists in this country in the management of urological medical pathology. The
      future is open, and it is in our hand to set up a training for urology residents
      within excellence and to be recognized both nationally and internationally as one
      of the great pillars of Spanish Urology. In this chapter we will analyze the
      current situation in the training of Spanish Urology Residents in urological
      medical pathology, and we will focus on training in functional urology and
      andrology.

PMID- 29336341
TI  - [Academic opportunities for Urology residents in Spain.]
AB  - The development of an academic career gives a new dimension to the chosen
      specialty. It consists in combining clinical activity with teaching and research
      activity. In the area of surgical specialties there is currently a lack of
      academic positions which is necessary to overcome to maintain the quality
      standards. Residency and the immediate posterior period it is a good time to star
      our academic career. This side of our specialty demands an additional effort,
      great motivation, clear and determined objectives and especially dedication.
      Considering Urology is a medical-surgical specialty it offers a perfect scenario
      for the development of research activity. In this article we review some of the
      available options to develop an academic career starting during residency. Among
      them we find some indispensable if one wants to develop an universitary career
      and others that facilitate the learning of scientific methodology, indispensable
      to elaborate a research project.

PMID- 29336342
TI  - [Homogeneity of the European training program. The role of the European Board of
      Urology.]
AB  - From its origins and acting through its specific committees, the E.B.U. has been
      dedicated to the improvement and standardization of urological training across
      Europe. Identifying minimal requirements for urology training, publishing a
      European Curriculum and defining basic rules for accreditation of educational
      activities, hence, offering a systematic assessment for the recognition of
      quality. Working through different dedicated committees, the E.B.U. oversees
      every aspect on the urological training in Europe. The Accreditation Committee
      sets standards for the accreditation of educational/scientific activities and
      ensures the proper evaluation of submissions for CME/ CPD accreditation. The
      Certification Committee oversees the appropriate implementation of the EBU
      Certification programme and ensures a thorough quality assessment process that
      aims to standardise urological training across Europe. Finally, the Examination
      Committee, that is structured into two sub-committees one for the In Service
      Assessment (I.S.A.) and the written F.E.B.U. examination (Part 1) and a second
      for the oral F.E.B.U. examination (Part 2). The committee works to ensure that
      all EBU examinations and associated assessment activities are thoroughly prepared
      and conducted in accordance with EBU's criteria.

PMID- 29336343
TI  - [On line learning in urologic surgery. The value of the 2.0 Web tools.]
AB  - The field of Surgery is under the pressure of accelerated change where
      technological cycles get shorter and shorter, sometimes transformational.
      Learning and training have gotten a key role because learning curves for new
      techniques directly affect patient's safety and learning cycles are slower. The
      traditional learning model within the urology department is overwhelmed. We need
      new training and learning methods. The aim of this article is to perform a
      critical analysis of the current status of learning in urological surgery and the
      challenges we face, evaluating how new information and communication technologies
      can help us to facilitate the learning process. We also present our initial
      experience with on line education on upper urinary tract laparoscopic and robotic
      surgery using the 2.0 Web tools.

PMID- 29336344
TI  - [The urologist of the future and new technologies.]
AB  - The last 25 years have brought about revolutionary changes for medicine and in
      particular for urology: internet was only in its infancy, medical records were
      written on paper, searches for medical information were done in the hospital
      library, medical articles were photocopied and our relationship with patients
      only existed face to face. Social networks had not yet appeared and even Google
      did not exist. Just imagine what might happen during the next 25 years, we're
      going to see even more radical changes. The urologist of the future is going to
      see the arrival of artificial intelligence, collaborative medicine, telemedicine,
      machine learning, the Internet of Things and personalized robotics; in the
      meantime, social media will continue to transform the interaction between
      physician and patient. The training of urologists will also be different thanks
      to new learning technologies such as virtual reality or augmented reality. IBM
      Watson Health through its system of artificial intelligence and its learning
      algorithms will become our essential travel companion. The urologist of the
      future, as well as physician, will have to acquire the necessary technological
      skills in order to use all these new tools which are already on the horizon.

PMID- 29336345
TI  - [The role of social media in academic training in Urology. Adequate use.]
AB  - Social media is characterized because all its services are participative. Users
      of 2.0 technologies can interact easily and openly with other people, share
      resources and communicate immediately and simultaneously. Research improves from
      participatory technologies by allowing groups to share reflections,
      methodologies, resources and results.The social media platform with greater
      diffusion and use in urology is possibly Twitter because it allows to realize
      what is known like "microblogging", the users generate comments and brief
      messages through the creation of "tweets". It is possible to determine that there
      are three broad areas from a scientific point of view in which social media are
      manifested: sharing research, resources and results. The use and applications of
      social media become a major responsibility in the area of health and urology,
      obviously for reasons of privacy, scientific rigor, ethics and the nature of the
      medical - legal content.

PMID- 29336346
TI  - Future of Urology training.
AB  - Urology has become more complex through the years, as it comprises increasingly
      sophisticated medical and surgical technologies such as advanced medical tumour
      therapies, and endourological, laparoscopicand robotic surgical techniques.
      Training in urology starts during medical school and once a medical student
      chooses to specialize on it, becomes life-long. Becoming a good urologist
      requires a highly qualified education and sufficient experience. To devise a
      training programme of high proficiency, several important factors must be
      considered. There are many studies in the literature revealing the thoughts of
      urology residents towards their training, needs and the realities. The aim of
      this chapter is to review the new technologies in urology training and show the
      new pathway of the future of training in urology.

PMID- 29336347
TI  - Electromigration and morphological changes in Ag nanostructures.
AB  - Electromigration (EM) as a structuring tool was investigated in Ag nanowires
      (width 300 nm, thickness 25 nm) and partly in notched and bow-tie Ag structures
      on a Si(1 0 0) substrate in ultra-high vacuum using a four-tip scanning tunneling
      microscope in combination with a scanning electron microscope. From simulations
      of Ag nanowires we got estimates of temperature profiles, current density
      profiles, EM and thermal migration (TM) mass flux distributions within the
      nanowire induced by critical current densities of 108 A cm-2. At room
      temperature, the electron wind force at these current densities by far dominates
      over thermal diffusion, and is responsible for formation of voids at the cathode
      and hillocks at the anode side. For current densities that exceed the critical
      current densities necessary for EM, a new type of wire-like structure formation
      was found both at room temperature and at 100 K for notched and bow-tie
      structures. This suggests that the simultaneous action of EM and TM is structure
      forming, but with a very small influence of TM at low temperature.

PMID- 29336348
TI  - Optimizing highly noncoplanar VMAT trajectories: the NoVo method.
AB  - We introduce a new method called NoVo (Noncoplanar VMAT Optimization) to produce
      volumetric modulated arc therapy (VMAT) treatment plans with noncoplanar
      trajectories. While the use of noncoplanar beam arrangements for intensity
      modulated radiation therapy (IMRT), and in particular high fraction stereotactic
      radiosurgery (SRS), is common, noncoplanar beam trajectories for VMAT are less
      common as the availability of treatment machines handling these is limited. For
      both IMRT and VMAT, the beam angle selection problem is highly nonconvex in
      nature, which is why automated beam angle selection procedures have not entered
      mainstream clinical usage. NoVo determines a noncoplanar VMAT solution (i.e. the
      simultaneous trajectories of the gantry and the couch) by first computing a
      [Formula: see text] solution (beams from every possible direction, suitably
      discretized) and then eliminating beams by examing fluence contributions. Also
      all beam angles are scored via geometrical considerations only to find out the
      usefulness of the whole beam space in a very short time. A custom path finding
      algorithm is applied to find an optimized, continuous trajectory through the most
      promising beam angles using the calculated score of the beam space. Finally,
      using this trajectory a VMAT plan is optimized. For three clinical cases, a lung,
      brain, and liver case, we compare NoVo to the ideal [Formula: see text] solution,
      nine beam noncoplanar IMRT, coplanar VMAT, and a recently published noncoplanar
      VMAT algorithm. NoVo comes closest to the [Formula: see text] solution
      considering the lung case (brain and liver case: second), as well as improving
      the solution time by using geometrical considerations, followed by a time
      effective iterative process reducing the [Formula: see text] solution. Compared
      to a recently published noncoplanar VMAT algorithm, using NoVo the computation
      time is reduced by a factor of 2-3 (depending on the case). Compared to coplanar
      VMAT, NoVo reduces the objective function value by 24%, 49% and 6% for the lung,
      brain and liver cases, respectively.

PMID- 29336349
TI  - Nanodoping: a route for enhancing electro-optic performance of bent core nematic
      system.
AB  - We report the effect of dispersion of barium titanate (BaTiO3) nanoparticles
      (BNPs) in a four ring bent core nematic (BCN) liquid crystal. Polarizing optical
      microscopy reveals the presence of a single nematic phase in pure and doped
      states. Polar switching has been observed in the bent core system and the value
      of spontaneous polarization (P s) increases with increase in doping concentration
      of BNPs in BCN. Dielectric study shows a lower frequency mode, which can be
      ascribed to the formation of cybotactic clusters. These clusters are also
      responsible for the observed polar switching in pure, as well as, in doped BCNs.
      Another higher frequency mode, observed only in pure BCN, indicates the rotation
      of molecules about their long molecular axis. The conductivity of doped samples
      is also found to decrease as compared to the pure BCN. This reduction helps in
      the minimization of negative effects caused by free ions in liquid crystal based
      devices. This study demonstrates that the interaction between BNPs and BCN
      molecules improves the P s, dielectric behaviour, viscosity and reduces the
      conductivity of pure BCN. Hence, nanodoping in a BCN is an effective method for
      the enhancement of electro-optic performances and will lead to the development of
      faster electro-optic devices.

PMID- 29336350
TI  - Mixed matrix membranes with fast and selective transport pathways for efficient
      CO2 separation.
AB  - To improve CO2 separation performance, porous carbon nanosheets (PCNs) were used
      as a filler into a Pebax MH 1657 (Pebax) matrix, fabricating mixed matrix
      membranes (MMMs). The PCNs exhibited a preferential horizontal orientation within
      the Pebax matrix because of the extremely large 2D plane and nanoscale thickness
      of the matrix. Therefore, the micropores of the PCNs provided fast CO2 transport
      pathways, which led to increased CO2 permeability. The reduced pore size of the
      PCNs was a consequence of the overlapping of PCNs and the polymer chains
      penetrating into the pores of the PCNs. The reduction in the pore size of the
      PCNs improved the CO2/gas selectivity. As a result, the CO2 permeability and
      CO2/CH4 selectivity of the Pebax membrane with 10 wt% PCNs-loading (Pebax-PCNs
      10) were 520 barrer and 51, respectively, for CO2/CH4 mixed-gas. The CO2
      permeability and CO2/N2 selectivity of the Pebax-PCNs-10 membrane were 614 barrer
      and 61, respectively, for CO2/N2 mixed-gas.

PMID- 29336351
TI  - Microwave absorption properties of reduced graphene oxide strontium
      hexaferrite/poly(methyl methacrylate) composites.
AB  - The key factors to consider when designing microwave absorber materials for
      eradication of electromagnetic (EM) pollution are absorption of incident EM waves
      and good impedance matching. By keeping these things in mind, flexible microwave
      absorber composite films can be fabricated by simple gel casting techniques using
      reduced graphene oxide (RGO) and strontium ferrite (SF) in a poly(methyl
      methacrylate) (PMMA) matrix. SF nanoparticles are synthesized by the well known
      sol-gel method. Subsequently, reduced graphene oxide (RGO) and SF nanocomposite
      (RGOSF) are prepared through a chemical reduction method using hydrazine. The
      structure, morphology, chemical composition, thermal stability and magnetic
      properties of the nanocomposite are characterized in detail by various
      techniques. The SF particles are found to be nearly 500 nm and decorated on RGO
      sheets as revealed by field emission scanning electron microscopy and
      transmission electron microscopy analysis. Fourier transform infrared and and
      Raman spectroscopy clearly show the presence of SF in the graphene sheet by the
      lower peak positions. Finally, ternary polymer composites of RGO/SF/PMMA are
      prepared by an in situ polymerization method. Magnetic and dielectric studies of
      the composite reveal that the presence of RGO/SF/PMMA lead to polarization
      effects contributing to dielectric loss. Also, RGO surrounding SF provides a
      conductive network in the polymer matrix which is in turn responsible for the
      magnetic loss in the composite. Thus, the permittivity as well as the
      permeability of the composite can be controlled by an appropriate combination of
      RGO and SF in PMMA. More than 99% absorption efficiency is achieved by a suitable
      combination of magneto-dielectric coupling in the X-band frequency range by
      incorporating 9 wt% of RGO and 1 wt% of SF in the polymer matrix.

PMID- 29336352
TI  - One-pot synthesis of a PtPd dendritic nanocube cage superstructure on graphenes
      as advanced catalysts for oxygen reduction.
AB  - How to use Pt economically and efficiently in the oxygen reduction reaction (ORR)
      is of theoretical and practical significance for the industrialization of the
      proton-exchange membrane fuel cells. In order to minimize Pt consumption and
      optimize the ORR performance, the ORR catalysts are recommended to be designed as
      a porous nanostructure. Herein, we report a one-pot solvothermal strategy to
      prepare PtPd dendritic nanocube cages via a galvanic replacement mechanism
      triggered by an I- ion. These PtPd alloy crystals are nanoporous, and uniformly
      dispersed on reduced graphene oxides (RGOs). The size of the PtPd dendritic
      nanocube cages can be easily tuned from 20-80 nm by controlling their
      composition. Their composition is optimized to be 1:5 Pt/Pd atomic ratio for
      these RGO-supported PtPd dendritic nanocages. This catalyst shows superior ORR
      performance with a specific activity of 2.01 mA  cm-2 and a mass activity of 4.45
      A  mg-1 Pt, far above those for Pt/C catalysts (0.288 mA  cm-2 for specific
      activity, and 0.21 A  mg-1 Pt for mass activity). In addition to ORR activity, it
      also exhibits robust durability with almost negligible decay in ORR mass activity
      after 10 000 voltammetric cycling.

PMID- 29336353
TI  - Perovskite nanocrystals: across-dimensional attachment, film-scale assembly on a
      flexible substrate and their fluorescence properties.
AB  - Perovskite nanocrystals (NCs), which are a good fluorescence candidate with
      excellent photoelectric properties, have opened new avenues in the fabrication of
      highly efficient solar cells, light-emitting diodes (LEDs), and other
      optoelectronic devices. Further advances will rely on the multitude of
      compositional, structural variants that enable the formation of lower
      dimensionality layered and three-dimensional (3D) perovskites with architectural
      innovations. In this work, the perovskite film was fabricated on a flexible
      substrate using simple dip-coating technology and 3D assemblies of perovskite NCs
      were obtained through an attachment process. Original perovskite NCs had a
      rectangular or square morphology with high particle uniformity and the narrow and
      symmetric fluorescence emission peak was adjustable at 515-527 nm. The
      controllable self-assembly of the micron size cuboid-like 3D assembly had an
      apparent enhancement on peak (111) in the x-ray diffraction (XRD) pattern.
      Surface ligands not only play a role in the attachment process but also keep the
      independence of each NC in 3D assemblies. Such assembly of the perovskite film
      maintained the original perovskite NCs fluorescence emission peak and narrow full
      width at the half-maximum (FWHM), which is of great importance for the
      investigation of future devices.

PMID- 29336354
TI  - An analytical poroelastic model for ultrasound elastography imaging of tumors.
AB  - The mechanical behavior of biological tissues has been studied using a number of
      mechanical models. Due to the relatively high fluid content and mobility, many
      biological tissues have been modeled as poroelastic materials. Diseases such as
      cancers are known to alter the poroelastic response of a tissue. Tissue
      poroelastic properties such as compressibility, interstitial permeability and
      fluid pressure also play a key role for the assessment of cancer treatments and
      for improved therapies. At the present time, however, a limited number of
      poroelastic models for soft tissues are retrievable in the literature, and the
      ones available are not directly applicable to tumors as they typically refer to
      uniform tissues. In this paper, we report the analytical poroelastic model for a
      non-uniform tissue under stress relaxation. Displacement, strain and fluid
      pressure fields in a cylindrical poroelastic sample containing a cylindrical
      inclusion during stress relaxation are computed. Finite element simulations are
      then used to validate the proposed theoretical model. Statistical analysis
      demonstrates that the proposed analytical model matches the finite element
      results with less than 0.5% error. The availability of the analytical model and
      solutions presented in this paper may be useful to estimate diagnostically
      relevant poroelastic parameters such as interstitial permeability and fluid
      pressure, and, in general, for a better interpretation of clinically-relevant
      ultrasound elastography results.

PMID- 29336355
TI  - Evaluation of cardiolipin nanodisks as lipid replacement therapy for Barth
      syndrome
AB  - Barth syndrome (BTHS) is a mitochondrial disorder characterized by cardiomyopathy
      and skeletal muscle weakness. Disease results from mutations in the tafazzin
      (TAZ) gene, encoding a phospholipid transacylase. Defective tafazzin activity
      results in an aberrant cardiolipin (CL) profile. The feasibility of restoring the
      intracellular CL profile was tested by in vivo administration of exogenous CL in
      nanodisk (ND) delivery particles. Ninety mg/kg CL (as ND) was administered to
      doxycycline-inducible taz shRNA knockdown (KD) mice once a week. After 10 weeks
      of CL-ND treatment, the mice were sacrificed and tissues harvested. Liquid
      chromatography-mass spectrometry of extracted lipids revealed that CL-ND
      administration failed to alter the CL profile of taz KD or WT mice. Thus,
      although CL-ND were previously shown to be an effective means of delivering CL to
      cultured cells, this effect does not extend to an in vivo setting. We conclude
      that CL-ND administration is not a suitable therapy option for BTHS.

PMID- 29336356
TI  - Tcf7l1 promotes transcription of Kruppel-likefactor 4 during Xenopus
      embryogenesis.
AB  - Kruppel-like factor 4 (Klf4) is a zinc finger transcriptionfactor and plays
      crucial roles in Xenopus embryogenesis. However, its regulation during
      embryogenesis is stillunclear. Here, we report that Tcf7l1, a key downstream
      transducerof the Wnt signaling pathway, could promote Klf4 transcription and
      stimulate Klf4 promoter activity in early Xenopus embryos. Furthermore,
      cycloheximide treatmentshowed a direct effect on Klf4 transcriptionfacilitated by
      Tcf7l1. Moreover, the dominant negative form of Tcf7l1(dnTcf7l1), which lacks N
      terminusof the beta-catenin binding motif, could still activate Klf4
      transcription, suggesting that thisregulation is Wnt/beta-catenin independent.
      Taken together, ourresults demonstrate that Tcf7l1 lies upstream of Klf4 to
      maintainits expression level during Xenopus embryogenesis.

PMID- 29336357
TI  - Distinctive roles of Rac1 and Rab29 in LRRK2 mediated membrane trafficking and
      neurite outgrowth.
AB  - Parkinson's disease (PD) associated leucine-rich repeat kinase 2 (LRRK2) mutants
      have shown pathogenic effects on variety of subcellular processes.Two small
      GTPases Rac1 and Rab29 have been indicated as possible downstream effectors
      participating in LRRK2 signaling but their detail mechanisms remain unclear. In
      this study, we have used biochemical and cell biology approaches to address
      whether two GTPases interact with LRRK2 and hence function differently in LRRK2
      mediated pathogenesis.Here we show thatRac1 and Rab29 specifically interact with
      LRRK2with higher affinity for Rab29and with different preference in functional
      domain binding. Mutant Rab29 but not Rac1 alters theendosome-to-TGN retrograde
      trafficking of a cargo protein cation-independent mannose-6-phosphate receptor
      (CI-M6PR) and its stability. On the other hand, overexpressedwild type Rab29 but
      not Rac1 rescue the altered retrograde membrane trafficking induced by the
      pathogenic mutant LRRK2G2019S. Furthermore, both Rac1 and Rab29 can rescue the
      neurite shortening in differentiated SH-SY5Y cells induced by LRRK2G2019S. Our
      study strongly suggests that Rac1 and Rab29 are involved in the distinct
      functions as downstream effectors in LRRK2 signaling pathways.

PMID- 29336358
TI  - Risk Factors, Regional Disparity and Trends of Ischemic Stroke Etiologic
      Subtypes.

PMID- 29336359
TI  - White Matter Lesions Predict Recurrent Vascular Events in Patients with Transient
      Ischemic Attacks.
AB  - BACKGROUND: White matter lesions (WMLs) are common findings in brain magnetic
      resonance imaging (MRI) and are strongly associated with stroke incidence,
      recurrence, and prognosis. However, the relationship between WMLs and transient
      ischemic attacks (TIAs) is not well established. This study aimed to determine
      the clinical significance of WMLs in patients with TIA. METHODS: A total of 181
      consecutive inpatients with first-ever TIA were enrolled. Brain MRIs within 2
      days of symptom onset were used to measure WML volumes. Recurrent vascular events
      within 1 year of TIA onset were assessed. The relationship between WMLs and
      recurrent risk of vascular events was determined by a multivariate logistic
      regression. RESULTS: WMLs were identified in 104 patients (57.5%). Age and ratio
      of hypertension were significantly different between patients with and without
      WMLs. The incidence of vascular events in patients with WMLs significantly
      increased in comparison to those without WMLs (21.15% vs. 5.19%, 95% confidence
      interval [CI]: 1.18-15.20, P = 0.027) after controlling for confounders.
      Furthermore, distributions of WML loads were found to be different between
      patients who developed vascular events and those who did not. WML volumes were
      demonstrated to be correlated with recurrent risks, and the fourth quartile of
      WML volumes led to an 8.5-fold elevation of recurrent risk of vascular events
      compared with the first quartile (95% CI: 1.52-47.65, P = 0.015) after adjusting
      for hyperlipidemia. CONCLUSION: WMLs occur frequently in patients with TIA and
      are associated with the high risk of recurrent vascular events, suggesting a
      predictive neuroimaging marker for TIA outcomes.

PMID- 29336360
TI  - Early Neurological Deterioration after Recanalization Treatment in Patients with
      Acute Ischemic Stroke: A Retrospective Study.
AB  - BACKGROUND: Early neurological deterioration (END) is a prominent issue after
      recanalization treatment. However, few studies have reported the characteristics
      of END after endovascular treatment (EVT) as so far. This study investigated the
      incidence, composition, and outcomes of END after intravenous recombinant tissue
      plasminogen activator (IV rt-PA) and EVT of acute ischemic stroke, and identified
      risk factors for END. METHODS: Medical records of patients who received
      recanalization treatment between January 1, 2014, and December 31, 2015 were
      reviewed. Patients were classified into IV rt-PA or EVT group according to the
      methods of recanalization treatment. The END was defined as an increase in the
      National Institutes of Health Stroke Scale (NIHSS) >=4 or an increase in Ia of
      NIHSS >=1 within 72 h after recanalization treatment. Clinical data were compared
      between the END and non-END subgroups within each recanalization group. RESULTS:
      Of the 278 patients included in the study, the incidence of END was 34.2%. The
      incidence rates of END were 29.8% in the IV rt-PA group and 40.2% in the EVT
      group. Ischemia progression (68.4%) was the main contributor to END followed by
      vasogenic cerebral edema (21.1%) and symptomatic intracranial hemorrhage (10.5%).
      Multivariate logistic regression showed that admission systolic blood pressure
      (SBP) >=160 mmHg (odds ratio [OR]: 2.312, 95% confidence interval [CI]: 1.105
      4.837) and large artery occlusion after IV rt-PA (OR: 3.628, 95% CI: 1.482-8.881)
      independently predicted END after IV rt-PA; and admission SBP >=140 mmHg (OR:
      5.183, 95% CI: 1.967-13.661), partial recanalization (OR: 4.791, 95% CI: 1.749
      13.121), and nonrecanalization (OR: 5.952, 95% CI: 1.841-19.243) independently
      predicted END after EVT. The mortality rate and grave outcome rate at discharge
      of all the END patients (26.3% and 55.8%) were higher than those of all the non
      END patients (1.1% and 18.6%; P < 0.01). CONCLUSIONS: END was not an uncommon
      event and associated with death and grave outcome at discharge. High admission
      SBP and unsatisfactory recanalization of occluded arteries might predict END.

PMID- 29336361
TI  - Muscle Magnetic Resonance Imaging for the Differentiation of Multiple Acyl-CoA
      Dehydrogenase Deficiency and Immune-mediated Necrotizing Myopathy.
AB  - BACKGROUND: Clinically, it is difficult to differentiate multiple acyl-CoA
      dehydrogenase deficiency (MADD) from immune-mediated necrotizing myopathy (IMNM)
      because they display similar symptoms. This study aimed to determine whether
      muscle magnetic resonance imaging (MRI) could be used for differential diagnosis
      between MADD and IMNM. METHODS: The study evaluated 25 MADD patients, confirmed
      by muscle biopsy and ETFDH gene testing, and 30 IMNM patients, confirmed by
      muscle biopsy. Muscles were assessed for edema and fatty replacement using thigh
      MRI (tMRI). Degrees and distribution patterns of fatty infiltration and edema in
      gluteus maximus and thigh muscles were compared. RESULTS: Total fatty
      infiltration and edema scores (median, [Q1, Q3]) were 4.00 (1.00, 15.00) and 0
      (0, 4.00) in MADD and 14.50 (8.00, 20.75) and 22.00 (16.75, 32.00) in IMNM,
      respectively, which were significantly more severe in IMNM than that in MADD (P =
      0.000 and P = 0.004, respectively). Edema scores for gluteus maximus, long head
      of biceps femoris, and semimembranosus were significantly higher in IMNM than in
      MADD (all P = 0.000). Fatty infiltration scores for anterior and medial
      compartments were significantly more severe in IMNM than that in MADD (all P =
      0.000). CONCLUSION: Different patterns of muscle involvement on tMRI can
      contribute to differential diagnosis between MADD and IMNM when clinical
      suspicions alone are insufficient, thereby reducing the need for muscle biopsy.

PMID- 29336362
TI  - Screening for SH3TC2, PMP2, and BSCL2 Variants in a Cohort of Chinese Patients
      with Charcot-Marie-Tooth.
AB  - BACKGROUND: SH3TC2, PMP2, and BSCL2 genes are related to autosomal recessive (AR)
      Charcot-Marie-Tooth (CMT) disease type 1, autosomal dominant (AD)-CMT1, and AD
      CMT2, respectively. Pathogenic variants in these three genes were not well
      documented in Chinese CMT patients. Therefore, this study aims to detect SH3TC2,
      PMP2, and BSCL2 pathogenic variants in a cohort of 315 unrelated Chinese CMT
      families. METHODS: A total of 315 probands from 315 unrelated Chinese CMT
      families were recruited from the Department of Neurology of Third Xiangya
      Hospital and Xiangya Hospital. We screened for SH3TC2 pathogenic variants in 84
      AR or sporadic CMT probands, PMP2 pathogenic variants in 39 AD or sporadic CMT1
      probands, and BSCL2 pathogenic variants in 50 AD or sporadic CMT2 probands, using
      polymerase chain reaction and Sanger sequencing. All these patients were out of
      315 unrelated Chinese CMT families and genetically undiagnosed after exclusion of
      pathogenic variants of PMP22, MFN2, MPZ, GJB1, GDAP1, HSPB1, HSPB8, EGR2, NEFL,
      and RAB7. Candidate variants were analyzed based on the standards and guidelines
      of American College of Medical Genetics and Genomics (ACMG). Clinical features
      were reevaluated. RESULTS: We identified three novel heterozygous variants such
      as p.L95V (c.283C>G), p.L1048P (c.3143T>C), and p.V1105M (c.3313G>A) of SH3TC2
      gene and no pathogenic variants of PMP2 and BSCL2 genes. Although evaluation in
      silico and screening in the healthy control revealed that the three SH3TC2
      variants were likely pathogenic, no second allele variants were discovered.
      According to the standards and guidelines of ACMG, the heterozygous SH3TC2
      variants such as p.L95V, p.L1048P, and p.V1105M were considered to be of
      uncertain significance. CONCLUSIONS: SH3TC2, PMP2, and BSCL2 pathogenic variants
      might be rare in Chinese CMT patients. Further studies to confirm our findings
      are needed.

PMID- 29336363
TI  - Utility and Safety of Intrathecal Methotrexate Treatment in Severe Anti-N-methyl
      D-aspartate Receptor Encephalitis: A Pilot Study.
AB  - BACKGROUND: Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a
      treatable autoimmune neurologic syndrome that occurs with or without tumor
      association. However, some severe cases are refractory to systemic immunotherapy.
      This pilot study aimed to evaluate the utility and safety of intrathecal
      methotrexate injection for severe patients with anti-NMDAR encephalitis who did
      not respond to first-line immunotherapy. METHODS: Intrathecal injections with
      methotrexate and dexamethasone were performed weekly in four legible patients
      within consecutive 4 weeks. Cerebrospinal fluid (CSF) was collected at baseline
      and each time of intrathecal injection for identification of anti-NMDAR antibody
      titers. RESULTS: Significant clinical improvement was observed in three patients
      associated with a stepwise decrease of CSF anti-NMDAR antibody titers (maximum:
      1/320 to minimum: 1/10). After 2 months of follow-up, they were able to follow
      simple commands and had appropriate interactions with people (modified Rankin
      scale [mRS] of 0-2). At 12 months of follow-up, they all had returned to most
      activities of daily life (mRS of 0), and no relapses were reported. One patient
      showed no clinical improvement and died of neurologic complications. CONCLUSIONS:
      Intrathecal treatment may be a potentially useful supplementary therapy in
      severely affected patients with anti-NMDAR encephalitis. Further large cohort
      study and animal experiment may help us elaborate the utility of intrathecal
      injection of methotrexate and its mechanism of action.

PMID- 29336364
TI  - Mechanism of Chronic Stress-induced Reduced Atherosclerotic Medial Area and
      Increased Plaque Instability in Rabbit Models of Chronic Stress.
AB  - BACKGROUND: Chronic stress contributes to increased risks of atherosclerotic
      diseases including heart disease, stroke, and transient ischemic attack. However,
      its underline mechanisms are poorly understood. This study aimed to elucidate the
      mechanism via which chronic stress exerts its effect on atherosclerosis (AS).
      METHODS: Fifty male New Zealand white rabbits were used. Aortic balloon-injury
      model was applied. Both social stress and physical stress methods were adopted to
      establish chronic stress models. The lumen stenotic degree, intimal and medial
      areas, maximum fibrous cap thickness, and plaque contents were measured with
      histological sections. Proteomic methods were applied to detect protein changes
      in abdominal aortas to identify the specialized mediators. Real-time reverse
      transcription-polymerase chain reaction was used for further verification and
      investigation. RESULTS: The stress rabbits exhibited lower body weight, worse fur
      state, more inactivity behavior, and higher serum cortisol level. Chronic stress
      was significantly associated with the decreased medial area and increased plaque
      instability, which was manifested by thinner fibrous caps, larger lipid cores,
      more macrophages, and new vessels but fewer smooth muscle cells and elastic
      fibers. After chronic stress, the apoptosis-related genes UBE2K, BAX, FAS,
      Caspase 3, Caspase 9, and P53 were upregulated, and BCL-2/BAX was down-regulated;
      the angiogenesis-related genes ANG and VEGF-A were also highly expressed in
      atherosclerotic arteries. CONCLUSIONS: Rabbit models of chronic stress were
      successfully established by applying both social stress and physical stress for 8
      weeks. Chronic stress can reduce AS tunica media and accelerate plaque
      instability by promoting apoptosis and neovascularization.

PMID- 29336365
TI  - IL1F7 Gene Polymorphism Is not Associated with Rheumatoid Arthritis
      Susceptibility in the Northern Chinese Han Population: A Case-Control Study.
AB  - BACKGROUND: Interleukin (IL)-37, also called IL1F7, is a natural inhibitor of
      inflammatory and immune responses. It is involved in the pathogenesis of
      rheumatoid arthritis (RA). This study aimed to investigate the role of IL1F7 gene
      polymorphism in RA susceptibility in a large cohort of patients. METHODS: Five
      selected single-nucleotide polymorphisms in IL1F7 genes (rs2723186, rs3811046,
      rs4241122, rs4364030, and rs4392270) were genotyped by TaqMan Allelic
      Discrimination in Northern Chinese Han population. The allele and the genotype
      were compared between patients with RA and healthy controls. Association analyses
      were performed on the entire data set and on different RA subsets based on the
      status of the anti-cyclic citrullinated peptide antibody and the rheumatoid
      factor by logistic regression, adjusting for age and gender. RESULTS: Trend
      associations were detected between rs2723186, rs4241122, rs4392270, and RA in
      Stage I (160 patients with RA; 252 healthy controls). Further validation in Stage
      II comprised 730 unrelated patients with RA (mean age: 54.9 +/- 12.6 years; 81.6%
      females) and 778 unrelated healthy individuals (mean age: 53.5 +/- 15.7 years;
      79.5% females). No significant differences in the distributions of alleles and
      genotypes were observed between the case and control groups in both the entire
      set and the different RA subsets. Disease activity and age of RA onset were also
      not associated with genotype distributions. CONCLUSION: IL1F7 gene polymorphism
      does not significantly influence RA susceptibility in the Northern Chinese Han
      population.

PMID- 29336366
TI  - Potential Value of Datura stramonium Agglutinin-recognized Glycopatterns in
      Urinary Protein on Differential Diagnosis of Diabetic Nephropathy and Nondiabetic
      Renal Disease.
AB  - BACKGROUND: Diabetic nephropathy (DN) is the most common and serious
      microvascular complication of diabetes. To date, the gold standard for
      identifying DN and nondiabetic renal disease (NDRD) is a renal biopsy; however,
      there is currently no reliable diagnostic marker to identify DN and NDRD in a
      noninvasive manner. This study aimed to investigate the different glycopatterns
      in urine specimens of DN patients and NDRD patients for a differential diagnosis.
      METHODS: In total, 19 DN patients and 18 NDRD patients who underwent renal
      biopsies between March 2015 and March 2016 at the Chinese People's Liberation
      Army General Hospital were enrolled in this study. A lectin microarray was used
      to investigate the glycopatterns in the urinary protein of the 37 patients. Ratio
      analysis and one-way analysis of variance were used to screen altered
      glycopatterns. Then, the altered glycopatterns between the DN and NDRD groups
      were verified by a urinary protein microarray among another 32 patients (15 with
      DN and 17 with NDRD), and receiver operating characteristic (ROC) curve analysis
      was used to determine the diagnostic value of the altered glycopatterns in
      differentiating DN and NDRD. Finally, lectin blotting was used to evaluate the
      altered glycosylation in protein level. RESULTS: The result of lectin microarrays
      revealed that the relative abundance of the (beta-1,4)-linked N-acetyl-D
      glucosamine (GlcNAc) recognized by lectin Datura stramonium agglutinin (DSA) was
      significantly higher in urinary protein in DN patients than that in NDRD patients
      (fold change >1.50, P < 0.001). Subsequently, the results of urinary protein
      microarrays were consistent with lectin microarrays (P < 0.05). Furthermore, the
      ROC curve showed that glycopatterns could effectively distinguish DN from NDRD
      patients (area under the ROC curve = 0.94, P < 0.001). DSA lectin blotting showed
      that glycoproteins, with a molecular weight of approximately 50,000, demonstrated
      a difference in urine samples between DN patients and NDRD patients. CONCLUSIONS:
      The relative abundance of (beta-1,4)-linked GlcNAc recognized by lectin DSA and
      urinary glycoprotein with a molecular weight of approximately 50,000 are
      significantly different between DN and NDRD patients, indicating that the
      glycopatterns could be used as potential biomarkers for a differential diagnosis.

PMID- 29336367
TI  - Reduction of Tat-interacting Protein 30 Expression Could be a Prognostic Marker
      in Bladder Urothelial Cancer.
AB  - BACKGROUND: Tat-interacting protein 30 (TIP30) has been reported to be a tumor
      suppressor, with reduced or absent expression in various tumors. However, its
      role in bladder urothelial cancer (BUC) has not been investigated. Therefore,
      herein, we investigated the expression of TIP30 protein in BUC and normal bladder
      mucosa and the clinical significance of TIP30 expression in the prognosis of BUC.
      METHODS: We reviewed data from 79 cases of BUC and 15 adjacent tissue samples
      from 79 patients treated at our institution between 2004 and 2007. TIP30
      expression was examined by immunohistochemistry. The relationship between TIP30
      expression and tumor stage, histological grade, and survival was analyzed.
      Differences between groups were evaluated using the t-test or matched-pairs test,
      and differences in the survival rates were analyzed with the log-rank test.
      RESULTS: TIP30 protein expression was significantly reduced in BUC tissue (t = 
      6.91, P < 0.05) compared with normal tissue samples, and in invasive bladder
      cancer (t = 10.89, P < 0.05) compared with superficial bladder cancer. TIP30
      protein expression differed significantly among different differentiated groups
      classified either according to the World Health Organization (2004, F = 17.48, P
      < 0.01) or World Health Organization (1973, F = 10.68, P < 0.01). TIP30 protein
      expression was significantly reduced in high-grade papillary urothelial carcinoma
      compared with papillary urothelial neoplasm of low malignant potential (P < 0.05)
      and low-grade papillary urothelial carcinoma (P < 0.05). Meanwhile, TIP30 protein
      expression was significantly reduced in Grade III BUC, compared with Grade I (P <
      0.05) and Grade II (P < 0.05). Patients with low TIP30 expression showed a higher
      incidence of disease progression than those with high TIP30 expression (t = 2.63,
      P < 0.05). Kaplan-Meier survival analysis showed a strong positive relationship
      between TIP30 expression and overall survival (OS) (chi2 = 17.29, P < 0.05).
      CONCLUSIONS: TIP30 expression was associated with clinical tumor stage in BUC,
      suggesting that it might play an important role in disease progression.
      Furthermore, TIP30 might predict postoperative OS. Thus, its evaluation might be
      useful for predicting prognosis.

PMID- 29336368
TI  - Glycosaminoglycan Content of the Lateral Compartment Cartilage in Knees
      Conforming to the Indications for Oxford Medial Unicompartmental Knee
      Arthroplasty.
AB  - BACKGROUND: The quality of the lateral compartment cartilage is important to
      preoperative evaluation and prognostic prediction of unicompartmental knee
      arthroplasty (UKA). Delayed gadolinium-enhanced magnetic resonance imaging of
      cartilage (dGEMRIC) enables noninvasive assessment of glycosaminoglycan (GAG)
      content in cartilage. This study aimed to determine the GAG content of the
      lateral compartment cartilage in knees scheduled to undergo Oxford medial UKA.
      METHODS: From December 2016 to May 2017, twenty patients (20 osteoarthritic
      knees) conforming to the indications for Oxford medial UKA were included as the
      osteoarthritis (OA) group, and 20 healthy volunteers (20 knees) paired by sex,
      knee side, age (+/-3 years), and body mass index (BMI) (+/-3 kg/m2) were included
      as the control group. The GAG contents of the weight-bearing femoral cartilage
      (wbFC), the posterior non-weight-bearing femoral cartilage (pFC), the lateral
      femoral cartilage (FC), and tibial cartilage (TC) were detected using dGEMRIC.
      The dGEMRIC indices (T1Gd) were calculated in the middle three consecutive slices
      of the lateral compartment. Paired t-tests were used to compare the T1Gd in each
      region of interest between the OA group and control group. RESULTS: The average
      age and BMI in the two groups were similar. In the OA group, T1Gd of FC and TC
      was 386.7 +/- 50.7 ms and 429.6 +/- 59.9 ms, respectively. In the control group,
      T1Gd of FC and TC was 397.5 +/- 52.3 ms and 448.6 +/- 62.5 ms, respectively. The
      respective T1Gd of wbFC and pFC was 380.0 +/- 47.8 ms and 391.0 +/- 66.3 ms in
      the OA group and 400.3 +/- 51.5 ms and 393.6 +/- 57.9 ms in the control group.
      Although the T1Gd of wbFC and TC tended to be lower in the OA group than the
      control group, there was no significant difference between groups in the T1Gd in
      any of the analyzed cartilage regions (P value of wbFC, pFC, FC, and TC was
      0.236, 0.857, 0.465, and 0.324, respectively). CONCLUSIONS: The GAG content of
      the lateral compartment cartilage in knees conforming to indications for Oxford
      medial UKA is similar with those of age- and BMI-matched participants without OA.

PMID- 29336369
TI  - Pedicle Subtraction Osteotomy with a Cage Prevents Sagittal Translation in the
      Correction of Kyphosis in Ankylosing Spondylitis.
AB  - BACKGROUND: Sagittal translation (ST) is an accidental event that surgeons
      commonly encounter during a spinal osteotomy in the correction of kyphosis in
      ankylosing spondylitis (AS). However, there is a paucity of effective techniques
      to prevent ST. The purpose of this study was to propose a pedicle subtraction
      osteotomy (PSO) with a cage as a method to prevent ST and to explore the efficacy
      and feasibility of this method in the treatment of kyphosis in AS. METHODS: We
      retrospectively reviewed 89 consecutive patients with AS kyphosis who underwent a
      PSO (Group B, 46 patients) or a PSO with a cage (Group A, 43 patients) from
      February 2009 to December 2013. Pre- and post-operative radiographic results were
      reviewed. ST and complications were analyzed in both groups. Clinical assessment
      was performed using the Scoliosis Research Society-22 (SRS-22) outcomes metric.
      The patients were followed up for at least 2 years. RESULTS: Group A achieved the
      same re-alignment of the kyphotic spine as Group B. Two (4.7%) of the 43 patients
      in Group A and 14 (30.4%) of the 46 patients in Group B had intraoperative ST
      (chi2 = 10.020, P = 0.002). Significant differences were identified between the
      two groups in the height change of the osteotomized column. SRS-22 scores
      improved significantly in both groups. Seven patients experienced neurologic
      complications (1 in Group A and 6 in Group B). Eight patients had cerebrospinal
      fluid leakage (2 in Group A and 6 in Group B). CONCLUSION: PSO with a cage
      significantly avoided ST during the osteotomy procedure and might represent a
      new, safe, and feasible choice for treating patients with AS kyphosis.

PMID- 29336370
TI  - Differences of Matrix Metalloproteinase 2 Expression between Left and Right
      Ventricles in Response to Nandrolone Decanoate and/or Swimming Training in Mice.
AB  - BACKGROUND: Matrix metalloproteinase (MMP)-2 plays an important role in the
      remodeling of left ventricles (LVs) and right ventricles (RVs). We investigated
      the differences of MMP-2 expression between LV and RV in response to nandrolone
      decanoate (ND), swimming training (ST), and combined ND and ST (NS) in mice,
      based on their structural, functional, and biochemical characteristics. METHODS:
      Totally 28 male C57B1 mice (6 weeks old; 20-23 g) were divided into four groups,
      including the control (n = 7), ND (n = 6), ST (n = 8), and NS (n = 7) groups.
      After respective treatments for 8 weeks, echocardiographic examination was used
      to assess the cardiac structure and function. Van Gieson stain was used to
      examine the fibrosis of LV and RV in response to different treatments, and
      Western blotting analysis was performed to explore different MMP-2 expressions
      between LV and RV in response to ND and/or ST. Analysis of variance was used for
      comparing the four groups. RESULTS: At 8 weeks, right ventricular dimension/body
      weight in the ND group was larger than the other three groups (F = 7.12, P <
      0.05) according to the echocardiographic examination. Fibrosis induced by ND
      administration was increased more in RV (2.59%) than that in LV (2.21%). MMP-2
      expression of the ND group in RV was significantly greater than the control and
      NS groups in RV and the corresponding ND group in LV. CONCLUSION: The
      experimental data support the hypothesis that ND administration induces greater
      MMP-2 expression increase in RV compared to LV, leading to consequent RV
      dilation.

PMID- 29336371
TI  - In vitro Flow Perfusion Maintaining Long-term Viability of the Rat Groin Fat
      Flap: A Novel Model for Research on Large-scale Engineered Tissues.
AB  - BACKGROUND: Large-scale muscle tissue engineering remains a major challenge. An
      axial vascular pedicle and perfusion bioreactor are necessary for the development
      and maintenance of large-scale engineered muscle to ensure circulation within the
      construct. We aimed to develop a novel experimental model of a large-scale
      engineered muscle flap from an existing rat groin fat flap. METHODS: A fat flap
      based on the superficial inferior epigastric vascular pedicle was excised from
      rats and placed into a perfusion bioreactor. The flaps were kept in the
      bioreactor for up to 7 weeks, and transdifferentiation of adipose to muscle
      tissue could have taken place. This system enabled myogenic-differentiation
      medium flow through the bioreactor at constant pH and oxygen concentration.
      Assessment of viability was performed by an immunofluorescence assay,
      histological staining, a calcein-based live/dead test, and through determination
      of RNA quantity and quality after 1, 3, 5, and 7 weeks. RESULTS:
      Immunofluorescence staining showed that smooth muscle around vessels was still
      intact without signs of necrosis or atrophy. The visual assessment of viability
      by the calcein-based live/dead test revealed viability of the rat adipose tissue
      preserved in the bioreactor system with permanent perfusion. RNA samples from
      different experimental conditions were quantified by spectrophotometry, and
      intact bands of 18S and 28S rRNA were detected by gel electrophoresis, indicating
      that degradation of RNA was minimal. CONCLUSIONS: Flow perfusion maintains the
      long-term viability of a rat groin engineered muscle flap in vitro, and a large
      scale vascularized muscle could be engineered in a perfusion bioreactor.

PMID- 29336372
TI  - Effects of Matricaria chamomilla Extract on Growth and Maturation of Isolated
      Mouse Ovarian Follicles in a Three-dimensional Culture System.
AB  - BACKGROUND: The aim of this study was to design and assess the effects of
      hydroalcoholic extract of Matricaria chamomilla (MC) on preantral follicle
      culture of mouse ovaries in a three-dimensional culture system. METHODS: Isolated
      preantral follicles were randomly divided into three main groups: the control
      group containing 10% fetal bovine serum without MC extract (G1), the first
      experimental group supplemented with 25 MUg/ml hydroalcoholic extract of
      chamomile (G2), and the second experimental group supplemented with 50 MUg/ml
      hydroalcoholic extract of chamomile (G3). RESULTS: After 12 days of culture, the
      survival rate (P < 0.05), antrum formation (P < 0.01), metaphase two oocytes (P <
      0.01), and the expression of PCNA (P < 0.05) and FSHR (P < 0.05) genes
      significantly decreased in G3 as compared with G1. On the other hand, at the last
      day of culture (day 12), the mean diameter of follicles cultured in the medium
      which was supplemented with 50 MUg/ml hydroalcoholic extract of chamomile
      significantly decreased as compared with the G1 (P < 0.05). In addition, the
      levels of progesterone and dehydroepiandrosterone hormones significantly
      increased in the medium of G3 relative to G1 (P < 0.01), while in the medium of
      G1, the level of 17beta-estradiol was significantly higher than that of other
      groups (P < 0.01). Reactive oxygen species levels of metaphase II oocytes were
      significantly decreased in G2 as compared with G1 (P < 0.01). CONCLUSION: Adding
      chamomile extract to culture media appeared to decrease follicular function and
      development.

PMID- 29336373
TI  - Advances of Long Noncoding RNAs-mediated Regulation in Reproduction.
AB  - OBJECTIVE: Advances in genomics and molecular biology have led to the discovery
      of a large group of uncharacterized long noncoding RNAs (lncRNAs). Emerging
      evidence indicated that many lncRNAs function in multiple biological processes
      and its dysregulation often causes diseases. Recent studies suggested that almost
      all regulatory lncRNAs interact with biological macromolecules such as DNA, RNA,
      and protein. LncRNAs regulate gene expression mainly on three levels, including
      epigenetic modification, transcription, and posttranscription, through DNA
      methylation, histone modification, and chromatin remodeling. LncRNAs can also
      affect the development of diseases and therefore be used to diagnose and treat
      diseases. With new sequencing and microarray techniques, hundreds of lncRNAs
      involved in reproductive disorders have been identified, but their functions in
      these disorders are undefined. DATA SOURCES: This review was based on articles
      published in PubMed databases up to July 10, 2017, with the following keywords:
      "long noncoding RNAs", "LncRNA", "placentation", and "reproductive diseases".
      STUDY SELECTION: Original articles and reviews on the topics were selected.
      RESULTS: LncRNAs widely participate in various physiological and pathological
      processes as a new class of important regulatory factors. In spermatogenesis,
      spermatocytes divide and differentiate into mature spermatozoa. The whole process
      is elaborately regulated by the expression of phase-specific genes that involve
      many strains of lncRNAs. Literature showed that lncRNA in reproductive cumulus
      cells may contribute to the regulation of oocyte maturation, fertilization, and
      embryo development. CONCLUSIONS: LncRNA has been found to play a role in the
      development of reproduction. Meanwhile, we reviewed the studies on how lncRNAs
      participate in reproductive disorders, which provides a basis for the study of
      lncRNA in reproduction regulation.

PMID- 29336375
TI  - Spontaneous Rupture and Thrombosis of Right Atrium.

PMID- 29336374
TI  - Radiotherapy for Gastrointestinal Stromal Tumors.
AB  - OBJECTIVE: Gastrointestinal stromal tumors (GISTs) are rare mesenchymal tumors of
      the gastrointestinal tract, which frequently cause intraabdominal metastases. The
      current standard of care is surgery for localized cases, and adjuvant imatinib is
      recommended for tumors with a high risk of recurrence. To date, radiotherapy has
      not been commonly accepted as a part of multimodality treatment approach other
      than palliation. However, recently published case reports and some small series
      suggest that radiotherapy is a valuable option for controlling locally
      progressive, drug-resistant disease. The aim of this review is to provide a
      viewpoint from a radiation oncologist concerning the management of GISTs,
      especially rectal GIST, and clarify the role and technical aspects of
      radiotherapy in the treatment approach. DATA SOURCES: A comprehensive search in
      PubMed using the keywords "radiotherapy for rectal GIST" and "rectal GIST" was
      undertaken. The literature search included the related articles after 1995. STUDY
      SELECTION: The main articles including rectal GIST case reports and GIST series
      containing rectal cases were the primary references. RESULTS: Surgery is the
      mainstay of treatment. However, to date, radiotherapy is included in the
      multidisciplinary treatment strategy of rectal GISTs in some circumstances with
      palliative, adjuvant, or definitive intent using different treatment doses and
      fields. CONCLUSIONS: Recently reported long-term local control rates indicate
      that GIST is a radiosensitive disease. This makes radiotherapy a valuable
      alternative in GIST management with curative intent, especially in patients who
      (1) cannot tolerate or are resistant to chemotherapy agents, (2) have an
      unresectable disease, (3) have a gross or microscopic residual disease after
      surgery, and (4) have a recurrent disease.

PMID- 29336376
TI  - Papillary Glioneuronal Tumor with an Excessive Angiomatous Component in an
      Elderly Man.

PMID- 29336377
TI  - Pulmonary Capillary Hemangiomatosis without Pulmonary Hypertension: An Early
      Stage of Disease?

PMID- 29336378
TI  - Reliability and Accuracy of Sepsis-related Organ Failure Assessment Scoring among
      Emergency Physicians.

PMID- 29336379
TI  - Recurrent Viral Infections Complicated with Cold Agglutinin Disease after
      Splenectomy for Thrombocytopenia.

PMID- 29336380
TI  - Iron Overload and Hepatitis C Virus Infection.

PMID- 29336381
TI  - Reply to "Iron Overload and Hepatitis C Virus Infection".

PMID- 29336382
TI  - Atrioventricular septal defects.

PMID- 29336383
TI  - Perioperative renal protection during cardiac surgery: A choice between dopamine
      and dexmedetomidine.

PMID- 29336384
TI  - Noninvasive ventilation using bipap: Expanding indications to post cardiac
      surgery care.

PMID- 29336385
TI  - Prophylaxis of postoperative nausea and vomiting after cardiac surgery in high
      risk patients: A randomized controlled study.
AB  - CONTEXT: The role of prophylaxis for postoperative nausea and vomiting (PONV) in
      cardiac surgery is under debate. AIMS: To study the risk factors for PONV after
      cardiac surgery and the role of betamethasone with or without droperidol for its
      prevention. SETTING AND DESIGN: Randomized open-label controlled study comparing
      standard care with PONV prophylaxis from February to November 2016. METHODS: Five
      hundred and two patients with planned nonemergent cardiac surgery were included.
      INTERVENTIONS: In the intervention arm, PONV prophylaxis (4 mg betamethasone
      with/without 0.625 mg droperidol) was administered in high-risk patients (two or
      more risk factors). Patients in the control arm were treated as per routine
      hospital practices. RESULTS: Female sex, past history of PONV, and migraines were
      associated with a significantly increased risk of PONV, while motion sickness,
      smoking status, and volatile anesthetics were not. Pain and treatment with
      nefopam or ketoprofen were associated with an increased risk of PONV. PONV was
      less frequent in the active arm compared to controls (45.5% vs. 54.0%, P = 0.063;
      visual analogic scale 10.9 vs. 15.3 mm, P = 0.043). Among the 180 patients
      (35.6%) with >=2 risk factors, prophylaxis was associated with reduced PONV
      (intention-to-treat: 46.8% vs. 67.8%, P = 0.0061; per-protocol: 39.2% vs. 69%, P
      = 0.0002). In multivariate analysis, prophylaxis was independently associated
      with PONV (odds ratio [OR]: 0.324, 95% confidence interval: 0.167-0.629, P =
      0.0009), as were female sex, past history of PONV, and migraines (OR: 3.027,
      3.031, and 2.160 respectively). No drug-related side effects were reported.
      CONCLUSION: Betamethasone with/without droperidol was effective in decreasing
      PONV in high risk cardiac surgical patients without any side effect.

PMID- 29336386
TI  - Retrospective study of complete atrioventricular canal defects: Anesthetic and
      perioperative challenges.
AB  - OBJECTIVE: The objective of this study was to highlight anesthetic and
      perioperative management and the outcomes of infants with complete
      atrioventricular (AV) canal defects. DESIGN: This retrospective descriptive study
      included children who underwent staged and primary biventricular repair for
      complete AV canal defects from 1999 to 2013. SETTING: A single-center study at a
      university affiliated heart center. PARTICIPANTS: One hundred and fifty-seven
      patients with a mean age at surgery of 125 +/- 56.9 days were included in the
      study. About 63.6% of them were diagnosed as Down syndrome. Mean body weight at
      surgery was 5.6 +/- 6.3 kg. METHODS: Primary and staged biventricular repair of
      complete AV canal defects. MEASUREMENTS AND MAIN RESULTS: A predefined protocol
      including timing of surgery, management of induction and maintenance of
      anesthesia, cardiopulmonary bypass, and perioperative intensive care treatment
      was used throughout the study. Demographic data as well as intraoperative and
      perioperative Intensive Care Unit (ICU) data, such as length of stay in ICU,
      total duration of ventilation including reintubations, and total length of stay
      in hospital and in hospital mortality, were collected from the clinical
      information system. Pulmonary hypertension was noted in 60% of patients from
      which 30% needed nitric oxide therapy. Nearly 2.5% of patients needed permanent
      pacemaker implantation. Thorax was closed secondarily in 7% of patients. In 3.8%
      of patients, reoperations due to residual defects were undertaken. Duration of
      hospital stay was 14.5 +/- 4.7 days. The in-hospital mortality was 0%.
      CONCLUSION: Protocolized perioperative management leads to excellent outcome in
      AV canal defect repair surgery.

PMID- 29336387
TI  - Dexmedetomidine for prevention of skeletal muscle ischaemia-reperfusion injury in
      patients with chronic limb ischaemia undergoing aortobifemoral bypass surgery: A
      prospective double-blind randomized controlled study.
AB  - BACKGROUND: Dexmedetomidine is a selective alpha-2 agonist used for sedation. It
      has also been shown to have myocardial protective effect and prevent ischemia
      reperfusion injury in off-pump coronary artery bypass patients. The aim of our
      study was to assess the effect of dexmedetomidine for prevention of skeletal
      muscle ischemia-reperfusion injury in patients undergoing aortobifemoral bypass
      surgery. METHODOLOGY: Sixty adult patients (Group dexmedetomidine n = 30, Group
      normal saline n = 30) undergoing aortobifemoral bypass surgery were recruited
      over 3 months. Randomization was done using a computer-generated random table.
      The attending anesthesiologist would be blinded to whether the drug/normal saline
      was being administered. He would consider each unlabeled syringe as containing
      dexmedetomidine and calculate the volume to be infused via a syringe pump
      accordingly. Dexmedetomidine infusion (1 mcg/kg) over 15 minutes was given as a
      loading dose, followed by maintenance infusion of 0.5 mcg/kg/h till 2 h
      postprocedure in Group dexmedetomidine (D) while the same volume of normal saline
      was given in the control Group C till 2 h postprocedure. Creatine phosphokinase
      (CPK) values were noted at baseline (T0), 6 h (T1), 12 h (T2), and 24 h (T3)
      after the procedure. Hemodynamic variables (heart rate [HR] and mean blood
      pressure [MAP]) were recorded at T0, T1, T2, and T3. Results were analyzed using
      unpaired Student's t-test, P < 0.05 was considered statistically significant.
      RESULTS: MAP and HR significantly decreased in Group D as compared to control
      group (P < 0.05). However, the decrease was never <20% of the baseline. The CPK
      values at 6, 12, and 24 h were statistically significant between the two groups.
      CONCLUSION: Dexmedetomidine prevents skeletal muscle ischemia-reperfusion injury
      in patients undergoing aortobifemoral bypass surgery.

PMID- 29336388
TI  - Assessment the effect of dexmedetomidine on incidence of paradoxical hypertension
      after surgical repair of aortic coarctation in pediatric patients.
AB  - OBJECTIVE: The aim of the study was to assess the effect of dexmedetomidine on
      the incidence of paradoxical hypertension in patients undergoing aortic
      coarctation repair. DESIGN: Randomized observational study. SETTING: University
      hospital and cardiac center. PATIENTS: The study included 108 pediatric patients
      with isolated aortic coarctation. METHODS: The patients were classified into two
      groups (each = 54): Group D: the patients received dexmedetomidine as a loading
      dose of 0.5 MUg/kg over 10 min followed by infusion 0.3 MUg/kg/h during surgery
      and continued for the first 48 postoperative hours. Group C: The patients
      received an equal amount of normal saline. The medication was prepared by the
      nursing staff and given to anesthetist blindly. The collected data included the
      heart rate, systolic and diastolic arterial blood pressure, incidence, onset,
      severity and treatment of paradoxical hypertension, fentanyl dose and end-tidal
      sevoflurane concentration, amount of blood loss and urine output. MAIN RESULTS:
      The heart rate, systolic and diastolic blood pressure decreased significantly
      with dexmedetomidine than Group C (P < 0.05). The incidence and severity of the
      paradoxical hypertension was lower with dexmedetomidine than Group C (P = 0.011,
      P = 0.017, respectively). The onset the paradoxical hypertension was earlier in
      Group C than dexmedetomidine (P = 0.026). The dose of fentanyl and sevoflurane
      concentration decreased significantly with dexmedetomidine (P = 0.034, P = 0.026,
      respectively). The blood loss decreased with dexmedetomidine (P = 0.020) and the
      urine output increased with dexmedetomidine (P = 0.024). The incidence of
      hypotension and bradycardia was more with dexmedetomidine (P < 0.05). CONCLUSION:
      Dexmedetomidine is safe in pediatric patients undergoing aortic coarctation
      repair. It minimized the incidence and severity of paradoxical hypertension. It
      decreased the required antihypertensive medications.

PMID- 29336390
TI  - Long-term quality of life postacute kidney injury in cardiac surgery patients.
AB  - BACKGROUND: Acute renal failure after cardiac surgery is known to be associated
      with significant short-term morbidity and mortality. There have as yet been no
      major reports on long-term quality of life (QOL). This study assessed the impact
      of acute kidney injury (AKI) and renal replacement therapy (RRT) on long-term
      survival and QOL after cardiac surgery. The need for long-term RRT is also
      assessed. MATERIALS AND METHODS: Patients who underwent cardiac surgery between
      2005 and 2011 (n = 6087) and developed AKI (RIFLE criteria, n = 570) were
      included. They were propensity-matched 1:1 to patients without renal impairment
      (control). Data were prospectively collected, and health-related QOL
      questionnaire was sent to patients who were alive at least 1-year postoperatively
      at the time of the study. RESULTS: There was no significant difference in the
      preoperative characteristics between the two groups (age, gender, left
      ventricular ejection fraction, procedure, urgency, logistic Euroscore),
      respectively. Median follow-up was 52 months. Survival data were available in all
      patients. Questionnaires were returned in 64% of eligible patients. Long-term
      survival was significantly lower, and QOL, in particular the physical aspect, was
      significantly worse for the AKI group as compared to non-AKI group (38.8 vs.
      44.2, P = 0.002), especially so in patients who required RRT. In alive
      respondents, despite an 18% (66/359) incidence of ongoing renal follow-up, the
      need for late RRT was only in 1.1% (4/359). CONCLUSION: AKI and especially the
      need for RRT following cardiac surgery are associated with increased long-term
      mortality as well as worse quality of life in a propensity-matched control group.

PMID- 29336389
TI  - A randomized controlled trial comparing the myocardial protective effects of
      isoflurane with propofol in patients undergoing elective coronary artery bypass
      surgery on cardiopulmonary bypass, assessed by changes in N-terminal brain
      natriuretic peptide.
AB  - OBJECTIVE: The objective of the study is to compare the myocardial protective
      effects of isoflurane with propofol in patients undergoing elective coronary
      artery bypass surgery on cardiopulmonary bypass (CPB), the cardio protection been
      assessed by changes in N-terminal brain natriuretic peptide (NT proBNP).
      Methodology and Design: This study is designed as a participant blinded,
      prospective randomized clinical trial. SETTING: Christian Medical College
      Hospital, Vellore, India. PARTICIPANTS: Patients undergoing elective coronary
      artery bypass surgery on CPB. INTERVENTION: Anesthesia was maintained with 0.8
      1.2 end tidal concentrations of isoflurane in the isoflurane group and in the
      propofol group, anesthesia was maintained with propofol infusion as described by
      Roberts et al. MEASUREMENTS: Hemodynamic data were recorded at frequent intervals
      during the surgery and up to 24 h in the Intensive Care Unit (ICU). The other
      variables that were measured include duration of mechanical ventilation, dose and
      duration of inotropes in ICU, (inotrope score), duration of ICU stay, NT proBNP
      levels before induction and 24 h postoperatively, creatine kinase-MB levels in
      the immediate postoperative, first and second day. RESULTS: Mean heart rate was
      significantly higher in propofol group during sternotomy, (P = 0.021). Propofol
      group had a significantly more number of patients requiring nitroglycerine in the
      prebypass period (P = 0.01). The increase in NT proBNP from preoperative to
      postoperative value was lesser in the isoflurane group compared to propofol even
      though the difference was not statistically significant. The requirement of
      phenylephrine to maintain mean arterial pressure within 20% of baseline,
      mechanical ventilation duration, inotrope use, duration of ICU stay and hospital
      stay were found to be similar in both groups. CONCLUSION: Propofol exhibit
      comparable myocardial protective effect like that of isoflurane in patients
      undergoing coronary artery bypass graft surgery. Considering the unproven
      mortality benefit of isoflurane and the improved awareness of green OT concept,
      propofol may be the ideal alternative to volatile anesthetics, at least in
      patients with good left ventricular function.

PMID- 29336391
TI  - Design and standardization of tools for assessing the perceived heart risk and
      heart health literacy in Iran.
AB  - OBJECTIVES: The aim is to achieve the standard tools for heart health, the
      present study aimed to design, develop, and standardize the two questionnaires of
      perceived heart risk scale (PHRS) and heart health literacy scale (HHLS).
      METHODS: The present study was a methodological research conducted on the
      residents of Kermanshah Province, Iran, using the multi-stage cluster sampling.
      Further, considering the scientific methods in the psychometric field, the design
      of the research questionnaires was conducted. In addition, the viewpoints of
      experts in different domains were qualitatively and quantitatively included to
      assess the validity of the questionnaires. To assess the reliability of the
      questionnaires, a sample including 31 subjects was first selected and studied
      within a fortnight's interval. Then, the reliability and validity of the scales
      were assessed using factor analysis and Cronbach's alpha in a sample of 771
      subjects. RESULTS: After reviewing the viewpoints of experts, the items were
      adjusted and implemented in the first sample at two stages. The results were
      indicative of the stability and acceptability of the Cronbach's alpha. In
      addition, the validity and reliability of the questionnaires were confirmed in
      the second sample too. CONCLUSION: According to the results of the present study,
      it can be concluded that the two questionnaires of PHRS and HHLS had acceptable
      reliability and validity.

PMID- 29336392
TI  - Transesophageal echocardiography evaluation of the aortic arch branches.
AB  - Visualization of aortic arch branches by transesophageal echocardiography has
      been technically challenging. Visualizing these vessels helps in identifying the
      extent of dissection of the aorta, assessing the severity of carotid artery
      stenosis, presence of atheromatous plaques, patency of the left internal mammary
      artery graft, confirmation of subclavian artery cannulation, confirming
      holodiastolic flow reversal in the left subclavian artery by spectral Doppler
      imaging in case of severe aortic regurgitation, and confirming the optimal
      position of the intraaortic balloon perioperatively. The information obtained is
      helpful for diagnosis, monitoring, and decision-making during aortic surgery.

PMID- 29336394
TI  - Commentary: Similar philosophy does not always synchronize.

PMID- 29336393
TI  - Cardiac surgery in a patient with implanted vagal nerve stimulator.
AB  - The prevalence of epilepsy worldwide is around 0.5%-2% of the population.
      Antiepileptic medications are the first line of treatment in most of the cases
      but approximately 25%-30% epilepsy patients are refractory to the single or
      combination therapy. The surgical option for temporal lobe epilepsy is temporal
      lobectomy, which has its inherent risk of neurological deficits after the
      surgery. Patients who are either refractory to combination therapy or do not want
      surgical temporal lobectomy are the candidates for electrical stimulation
      therapy. Refractory cases require implantable device such as vagal nerve
      stimulator (VNS). We are reporting perioperative management of a patient, with an
      implanted VNS, posted for pericardiectomy. It is important for the
      anesthesiologist to be familiar with the mechanism of VNS for proper
      perioperative care.

PMID- 29336395
TI  - Tricuspid valve straddling: An uncommon cause of left ventricular outflow tract
      obstruction in transposition of great artery with ventricular septal defect.
AB  - Transposition of great arteries (TGA) can be associated with left ventricle
      outflow tract (LVOT) obstruction. In the presence of ventricular septal defect
      (VSD), septal leaflet of tricuspid valve may prolapse through perimembranous VSD
      or rarely tricuspid valve tissue may override to produce LVOT obstruction.
      Occasionally, this may be mistaken for vegetation due to associated pulmonary
      valve endocarditis. We report a case of d-TGA with presumptive pulmonary valve
      endocarditis and LVOT obstruction that was found to be due to tricuspid valve
      straddling on transesophageal echocardiography, resulting in change in the
      surgical plan and thus avoiding catastrophe.

PMID- 29336396
TI  - Right atrial fibroma in an adult patient.
AB  - Left atrial fibroma as a benign tumor is an exceedingly rare left atrial mass. It
      has various clinical signs and symptoms and sometimes leads to serious
      complications such as lethal arrhythmia and death. We report a case of right
      atrial fibroma in a 40-year-old male who presented with dyspnea and atrial
      fibrillation. Transthoracic echocardiography revealed a large sessile mass
      attached to interatrial septum near the coronary sinus valve in the right atrium.
      The patient underwent surgical resection of tumor through the right atrium. The
      postoperative course was unremarkable. Histopathological examination showed that
      it was a fibroma. The 6-month follow-up revealed that the patient was in well
      condition with no evidence of tumor recurrence.

PMID- 29336397
TI  - Large inferolateral left ventricular aneurysm.
AB  - The majority of cardiac left ventricular aneurysms involve the anterior and/or
      apical wall. We present a case of a 50-year-old man with heart failure caused by
      a large inferolateral left ventricular aneurysm and associated mitral
      regurgitation, managed by aneurysmectomy, mitral valvuloplasty, and surgical
      revascularization.

PMID- 29336398
TI  - Concomitant neurogenic and vascular thoracic outlet syndrome due to multiple
      exostoses.
AB  - We report a rare case of multiple hereditary exostosis where patient presented
      with bilateral base of neck exostoses with concurrent compression of brachial
      plexus and subclavian artery and vein. The patient was a young 26-year-old woman
      with chief complaints of pain in the left upper extremity, paresthesia in the
      left ring and little finger, and weakness in hand movement and grip. On referral,
      history, physical examination, radiological imaging, and electrodiagnostic tests
      evaluated the patient. Due to severe pain and disability in performing routine
      activities, surgical intervention was necessary. In the current case, the patient
      had thoracic outlet syndrome with concomitant venous, arterial, and neurogenic
      sub types. Radial pulse returned and pain associated with brachial plexus
      compression was resolved after the surgery.

PMID- 29336399
TI  - Commentary: Comments on thoracic outlet syndrome.

PMID- 29336400
TI  - Successful resolution with apixaban of a massive left atrial appendage thrombus
      due to nonrheumatic atrial fibrillation: A case report and review.
AB  - A 32-year-old woman with a past medical history of paroxysmal atrial
      fibrillation, long QT syndrome, and implantation of an automatic iimplantable
      cardioverter-defibrillator (AICD) following cardiac arrest presented with
      disabling symptoms of paroxysmal atrial fibrillation due to recurrent AICD
      shocks. Before curative ablation, transesophageal echocardiography was performed
      to assess for existing thrombi. This is a rare case of successful resolution with
      apixaban of a massive left atrial appendage thrombus due to non-rheumatic atrial
      fibrillation that was successfully treated with apixaban.

PMID- 29336401
TI  - Bleeding in the lung complicates a routine intracardiac repair: What went
      wrong!!!
AB  - Cyanotic congenital heart disease presents an increased tendency to bleed in view
      of subtle coagulation defects. Airway bleeding can be particularly difficult to
      manage while maintaining an adequate ventilation. An isolated lung bleed with the
      exclusion of possible traumatic, medical and surgical causes of bleeding, should
      alert the attending anesthesiologist to the possibility of the collateral-related
      bleeding. Preoperative coil embolization remains an important initial management
      step in a case of tetralogy of Fallot (TOF) with major aortopulmonary
      collaterals. Nevertheless, the coiling of the collaterals in certain specific
      case scenarios is not feasible, rendering the management of a lung bleed, all the
      more challenging. We, hereby discuss a case of a 7-year-old girl with a massive
      endotracheal bleed at the time of weaning from cardiopulmonary bypass after
      corrective surgery for TOF. The subsequent approach and management are discussed.
      The optimal management of tetralogy with collaterals mandates an effective
      communication among the cardiologist, radiologist, anesthesiologist, and the
      surgeon.

PMID- 29336402
TI  - Mechanical discordance between left atrium and left atrial appendage.
AB  - During standard transesophageal echocardiographic examinations in sinus rhythm
      (SR) patients, the left atrial appendage (LAA) is not routinely assessed with
      Doppler. Despite having a SR, it is still possible to have irregular activity in
      the LAA. This situation is even more important for SR patients where assessment
      of the left atrium is often foregone. We describe a case where we encountered
      this situation and briefly review how to assess the left atrium and its appendage
      in such a case scenario.

PMID- 29336403
TI  - Superior vena cava clamping during thoracic surgery: Implications for the
      anesthesiologist.
AB  - Resection and reconstruction of the SVC is a challenging Intraoperative situation
      owing to the potential complications after clamping a patent vessel. Hemodynamic
      imbalance and neurological effects of SVC clamping can be life threatening. These
      complications can be prevented by careful intraoperative monitoring and
      management. Anaesthesiologist must be aware of different options to manage such
      challenging situations.

PMID- 29336404
TI  - Role of transesophageal echocardiography during left atrial appendage occlusion
      device closure in a patient with non-valvular atrial fibrillation and
      angiodysplasia of the colon.
AB  - Atrial fibrillation is the most common arrhythmia associated with significant
      mortality and morbidity secondary to thrombo-embolism. To prevent this thrombo
      embolism oral anticoagulation therapy is the recommended treatment. In patients
      with contraindications to oral anticoagulation therapy, percutaneous left atrial
      appendage occlusion device is indicated. TEE is essential to guide in all the
      stages of LAA device deployment. Right from pre-procedure screening, to guiding
      during deployment, to rule out any complications and post-procedure surveillance
      and monitoring long term outcomes.

PMID- 29336405
TI  - Looking inside the third generation left ventricular assist device using color
      doppler transesophageal echocardiography.
AB  - HeartWare is a third-generation continuous flow left ventricular assist device
      (LVAD) and generates centrifugal pattern of blood flow. In the perioperative
      setting, interrogating the HeartWare devices is very difficult due to the
      interference of the Doppler by the impeller frequency and generation of the
      waterfall artifact. We present a case where using color Doppler a view "inside"
      the impeller can be seen which corresponds to the centrifugal flow of blood. With
      time, these images can be looked into in pathological states such as pump
      thrombosis, to come to a more meaningful conclusion regarding the flow of blood
      within the centrifugal chamber. Newer technologies are constantly evolving to
      give us more meaningful insights into the flow of blood within the heart
      chambers. We believe similar technologies can be applied to see the flow of blood
      inside the LVAD devices.

PMID- 29336406
TI  - Quadricuspid aortic valve: A rare intraoperative diagnosis by transesophageal
      echocardiography.
AB  - Quadricuspid aortic valve (QAV) is a rare congenital anomaly frequently
      associated with other anomalies particularly coronary anomalies. It may be
      detected on transthoracic or transesophageal echocardiography. We present here a
      case report of a 27-year-old male patient with a QAV, the valve being regurgitant
      and requiring aortic valve replacement. It has been reported as isolated case
      reports in the literature and various theories exist to the development of QAV.
      The diagnosis requires a high degree of suspicion and a detailed assessment, and
      if asymptomatic, then patients need to be carefully followed up for the
      development of aortic regurgitation.

PMID- 29336407
TI  - Unknown left atrial appendage mass! real-time three-dimensional transesophageal
      echocardiography helps in identification.
AB  - Left Atrial Appendage (LAA) is the most contractile part of Left atrium. It is
      also the most frequent place for thrombus formation that may lead to disastrous
      consequences. Complete trasoesophageal echocardiography examination always
      includes assessing LAA but sometimes unusually placed pectinate muscle, which is
      a normal structure may give baffling shadow that can only be interpreted
      correctly by Real time 3D echocardiography.

PMID- 29336408
TI  - Pneumopericardium after minimally invasive atrial septal defect closure.
AB  - Minimally invasive atrial septal defect (ASD) closure is a commonly performed
      cardiac surgical procedure and has good outcome. We report an interesting chest X
      ray showing pneumopericardium in a patient who underwent ASD closure using a
      minimally invasive approach.

PMID- 29336409
TI  - Large thymus tumor with invasion into superior vena cava: Transesophageal
      echocardiography proved to be helpful during surgery.

PMID- 29336410
TI  - Spontaneous coronary artery dissection in anabolic steroid misuse.

PMID- 29336411
TI  - Unsolved enigma of atrial myxoma with biventricular dysfunction.

PMID- 29336412
TI  - In response to: Unsolved enigma of atrial myxoma with biventricular dysfunction.
AB  - Thanks to Raut et al.[1] for appreciating our efforts in managing the case of
      biatrial myxomas. A brief discussion is warranted here on the types, size of
      cardiac myxomas, interleukin 6 (IL-6) levels, left ventricle (LV) dysfunction,
      and their relation. IL-6 is a pleiotropic cytokine with a variety of biologic
      activities, including differentiation of B cell, thymocytes, and T cells;
      activation of macrophages; and stimulation of hepatocyte to produce acute-phase
      proteins such as C-reactive protein.[2],[3] It is also said to have paracrine,
      endocrine, and autocrine growth functions.[3].

PMID- 29336413
TI  - Erratum: Comparison of the renoprotective effect of dexmedetomidine and dopamine
      in high-risk renal patients undergoing cardiac surgery: A double-blind randomized
      study.
AB  - [This corrects the article DOI: 10.4103/aca.ACA_57_17.].

PMID- 29336414
TI  - Reflections about the Impact of Infertility on Female Sexual Function.

PMID- 29336415
TI  - Retrospective Study to Determine Stability of Mandibular Setback Surgery using
      Bilateral Sagittal Split Osteotomy Technique.
AB  - Background Bilateral sagittal split osteototomy of mandible is one of the most
      commonly performed orthognathic surgical procedure performed in the mandible.
      According to hierarchy of stability, mandibular setback procedure is considered
      to be relatively unstable procedure and chances of relapse are higher. Objective
      We conducted this study to determine the skeletal stability of mandibular setback
      procedure using bilateral sagittal split osteotomy technique in Nepalese
      population. Method Lateral cephalograms of 14 patients who underwent mandibular
      setback using bilateral saggital split osteotomy were taken pre-operatively (P1),
      immediate postoperatively (P2) and eight months to one year post-operatively
      (P3). Cephalometric tracing was done for all the cephalograms. Various parameters
      of Burstone's hard and soft tissue, Steiner's and McNamara analysis were used in
      the study to determine angular and linear changes following surgery. After
      tracing the cephalograms, changes between P1- P2, P1-P3 and P2-P3 were
      calculated. Mean difference in changes between P1-P2, P1-P3 and P2-P3 were
      compared using paired t test. P value less than 0.05 was considered to be
      significant. Data analysis was done using SPSS software version 20. Result Mean
      setback at Pogonion was 3.03 mm whereas at point B were 4.64 mm. Relapse at
      Pogonion was 0.03 mm and relapse at point B were 0.02 mm. Mean change in point A
      Nasion-point B angle was 5.1 degrees whereas mean changes in NA-Pogonion angle
      were 4.69 degrees. Conclusion There were significant changes in angular as well
      as horizontal parameters at P2 but there were no significant changes in those
      parameters at P3. This is a preliminary study that we have carried out at our
      institution with smaller sample size thus we recommend a study with larger sample
      size and long term follow up.

PMID- 29336416
TI  - Work Related Musculoskeletal Morbidity among Tailors: A Cross Sectional Study in
      a Slum of Kolkata.
AB  - Background Musculoskeletal disorders comprise the single largest group of work
      related illnesses in developing countries. Sedentary working style with wrong
      posture for long time is considered to be an important risk factor, which is
      largely modifiable. Objective This study was performed to determine the
      prevalence and find out the factors associated with Musculoskeletal disorders
      among the workers involved in tailoring occupation. Method A descriptive
      community based cross-sectional study was conducted in the urban slums of Chetla,
      Kolkata on March and April, 2015. One hundred and ten (110) out of 383 resident
      tailors in the area were chosen by simple random sampling and interviewed by
      approaching them in their work place. Descriptive statistics and multivariable
      logistic regression were used Result Using Nordic Musculoskeletal questionnaire,
      Musculoskeletal disorders was found among 65.45% of tailors. The most commonly
      affected site was neck (41.8%) followed by lower and upper back. In bivariate
      analysis, musculo-skeletal disorders was found to be significantly associated
      with age more than 45 years [OR (95% CI)= 3.35 (1.30- 8.60)], working for > 10
      years [OR (95% CI)= 7.01 (2.93-16.79)*], working > 8 hours per day [OR (95% CI)=
      2.75 (1.20-6.20)], full time job [OR (95% CI)= 2.41 (1.08-5.39)] and unfavourable
      workstation ergonomic [OR (95% CI)= 2.40 (1.10-5.40)], whereas in multivariate
      analysis age, sex, duration in the profession [AOR (95%CI= 4.40 (1.40- 14.30)],
      working hours per day [AOR (95%CI= 7.20 (1.80-27.80)], and unfavourable
      workstation ergonomic [AOR (95%CI)= 3.50 (1.26-9.80)] remained significant.
      Conclusion A multidimensional approach including appropriate technique in terms
      of operators' posture and ergonomically sound workstation are required to avoid
      the debilitating effect of Musculoskeletal disorders among the workers.

PMID- 29336417
TI  - Compliance and its Determinants Regarding Iron and Folic Acid Supplementation
      during Pregnancy in Kathmandu, Nepal.
AB  - Background Iron deficiency anemia is one of the major public health problems
      mostly affecting pregnant women of developing countries like Nepal. Kathmandu,
      the capital city of Nepal, has considerably high prevalence of anemia, which is
      attributed to inadequate dietary iron and problems of compliance to iron and
      folic acid supplementation. Objective This descriptive study aimed to identify
      the levels of and determinants associated with compliance regarding Iron and
      folic acid supplementation among pregnant women in Kathmandu, Nepal. Method The
      study was conducted in Paropakar Maternity and Women's Hospital in Kathmandu.
      Systematic random sampling was done to select a total of 406 samples that were
      either handed questionnaire for self-administration or interviewed. The chi2 test
      and multiple linear regressions were used for statistical analysis. Result The
      findings showed 73.2% of the respondents had high compliance, 12.8% moderate
      compliance, and 14% low compliance to iron and folic acid supplementation. More
      than half of the respondents had insufficient knowledge regarding anemia, iron
      deficiency and iron and folic acid supplementation. Multiple linear regression
      revealed that perceived severity, perceived barriers and social support were
      determinants of compliance to iron and folic acid supplementation (p<0.05).
      Conclusion This study infers that there is a lack of knowledge and awareness
      regarding anemia, iron deficiency, and iron and folic acid supplementation among
      pregnant women, and improvement in social support and perception of severity of
      the disease, and minimization of associated barriers may lead to better outcome
      in terms of compliance to iron and folic acid supplementation among pregnant
      women.

PMID- 29336418
TI  - Dysmenorrhea and Stress among the Nepalese Medical Students.
AB  - Background Dysmenorrhea is the most common gynecological disorder in women of
      reproductive age with implications as reduced quality of life and school
      absenteeism. Mental stress is possibly the most important known predisposing
      factor for primary dysmenorrhea. Objective This study aims to assess the
      relationship between stress and dysmenorrhea amongst the Nepalese medical
      students. Method This is cross-sectional descriptive study, conducted from 1st
      Dec. 2012 to 31st Jan. 2013. The study was conducted in Kathmandu University
      School of Medical Sciences. A total of 184 participants consented for this study
      and each one was given a questionnaire to complete. This study included only
      unmarried nulliparous, healthy (all through first to final years) female medical
      students, in age group of 16 to 24 years. Result The mean age of the participants
      was 19.43(+/-3.9) years. Among them, 67% of the participants experienced
      dysmenorrhea. Of them, 85% experienced increase in frequency and severity of
      dysmenorrhea after joining medical college. Similarly, 65% of participants
      considered medical education to be stressful. Of participants experiencing
      dysmenorrhea, 29.45% missed classes and 17.39% participants had positive family
      history of dysmenorrhea in first and second degree relatives. Conclusion The
      present study indicated a positive relationship between psychological stress and
      dysmenorrhea. Dysmenorrhea is the leading cause of recurrent short-term school
      absence in young ladies; this issue certainly needs to be addressed.

PMID- 29336419
TI  - Variable Presentations of Sinonasal Polypoid Masses: A Tertiary Institution
      Experience.
AB  - Background Lesions of the sinonasal area are varied, but they mostly present as
      polypoid masses which require meticulous work-up to reach at the most probable
      diagnosis. Objective Analysis of polypoid sinonasal masses in terms of etiology,
      clinical presentations, brief demographic profile, clinico-histologic correlate
      where possible, and follow-up results. Method In this descriptive, longitudinal
      study, 198 patients with polypoid sinonasal masses attending the otolaryngology
      clinic of a tertiary teaching institute were selected using proper selection
      criteria and analyzed through a pre-set proforma and algorithm for a diagnostic
      work-up (that included histopathology where necessary). Result Common
      presentations were nasal obstruction (~89%), discharge (~70%) and hyposmia
      (~22%). Though nearly 87% was clinically benign and 8% indeterminate, therapeutic
      and diagnostic interventions (including histopathology) showed 91% truly benign,
      of which polyposis formed the bulk. Sensitivity of clinical detection was 75% for
      benign lesions and 62% for malignancies. Diagnosis depended on histopathology in
      52.52% cases, including the clinically malignant, the "grey zone", and more than
      40% of the clinically benign lesions. There was male predilection (2.16 for
      benign lesions and 1.57 for malignant), rural preponderance, and above 60% of the
      patients were within 50-70 years. There was ~26% recurrence in the follow-up
      period of a minimum of one year, predominantly in polyposis (29.55%) and
      malignancies (~39%). Conclusion Presentations of polypoid sinonasal masses are
      variable, etiology of which is mostly benign. Proper clinico-histologic correlate
      is necessary for correct diagnosis. A low threshold of suspicion is required
      because of this variability, necessitating follow-up for further evaluation.

PMID- 29336420
TI  - Perception on Informed Consent Regarding Nursing Care Practices in a Tertiary
      Care Center.
AB  - Background Consent for care procedures is mandatory after receipt of adequate
      information. It maintains patient's rights and autonomy to make thoughtful
      decisions. Poor communication often leads to poor health quality. Objective To
      assess hospitalized patients' perception on informed consent regarding nursing
      care practices in a tertiary care center. Method This is a descriptive cross
      sectional study among 113 admitted patients conducted in February 2012 at
      Dhulikhel Hospital, Nepal. Patients of various wards were selected using
      purposive non-probability sampling with at least 3 days of hospitalization. Close
      ended structured questionnaire was used to assess patients' perception on three
      different areas of informed consent (information giving, opportunity to make
      decision and taking prior consent). Result Among the participants 71.6% perceived
      positively regarding informed consent towards nursing care practices with a mean
      score of 3.32 +/- 1.28. Patients' perception on various areas of informed consent
      viz. information giving, opportunities to make specific decision and taking prior
      consent were all positive with mean values of 3.43+/-1.12, 2.88+/-1.23, 3.65+/
      1.49 respectively. Comparison of mean perception of informed consent with various
      variables revealed insignificant correlation (p-value >0.05) for age, educational
      level and previous hospitalization while it was significant (p-value < 0.05) for
      communication skills of nurses. Conclusion Majority of patients have positive
      perception on informed consent towards nursing care practices. Communication
      skills of nurses affect the perception of patients' regardless of age, education
      level and past experiences.

PMID- 29336421
TI  - Reflux Symptom Index and Reflux Finding Score in Diagnosis of Laryngopharyngeal
      Reflux.
AB  - Background Although laryngopharyngeal reflux is a common condition encountered in
      otolaryngological practice, its diagnosis is not very easy because of its
      indistinct symptoms Objective To assess the efficacy of proton pump inhibitors
      versus proton pump inhibitors with lifestyle modification in patients with
      laryngopharyngeal reflux. Method Prospective, analytical study conducted in
      Department of Otorhinolaryngology and Head and Neck Surgery at Dhulikhel
      Hospital, Kathmandu University Hospital between January 2015 to January 2016.
      Eighty two patients with laryngopharyngeal reflux having Reflux symptom index >
      13 and Reflux finding score > 7 were included. Patients were divided into 2
      groups. Group A comprised of patients treated with proton pump inhibitors alone
      and Group B with Proton pump inhibitors with lifestyle modification. Pre and post
      therapeutic reflux finding score and reflux symptom index were compared. Result
      The mean reflux symptom index score difference before and after treatment in
      group A was 16.70 and group B was 14.58. Similarly, mean reflux finding score
      difference before and after treatment in group A was 8.68 and group B was 9.92.
      Comparison of reflux finding score and reflux symptom index scores before and
      after treatment revealed improvement in both groups and the difference was
      statistically significant (p<0.001). However, comparison of pre and post
      therapeutic and scores between group A and B, showed no statistical significance.
      Conclusion The extent of symptomatic improvement correlated positively with both
      proton pump inhibitor therapy alone as well as with proton pump inhibitor therapy
      along with lifestyle modification. Although addition of lifestyle modification
      offered incremental benefit for treating laryngopharyngeal reflux, it was not
      found to be statistically significant.

PMID- 29336422
TI  - Cold Pressor Test in Borderline Hypertensive University Students.
AB  - Background Hyperactive sympathetic reaction is an important factor for
      development of hypertension in young individuals. The stress induced increase in
      blood pressure recovers within very short period of time and those with
      exaggerated stress induced cardiovascular response at young age have a high risk
      of blood pressure elevation in future. Objective To determine the cardiovascular
      reactivity in response to cold and to correlate its relation with factors such as
      smoking, family history and physical activity. Method Study was conducted in the
      Department of Pharmacy, Kathmandu University from July to November, 2015. Resting
      blood pressure was recorded using sphygmomanometer in sitting position after 5
      minutes of rest. Out of 130 volunteers, 34 were found to be prehypertensive and
      equal number of normotensive were recruited randomly to perform the test. The
      subjects were directed to immerse his/her right hand up to the wrist in cold
      water of 10C for 1 minute. The blood pressure was recorded just before the hand
      was taken out of the water and then 1.5 minutes and 4 minutes after the
      withdrawal. Data was analyzed by Student's t test using Microsoft Excel 2007.
      Result Systolic and diastolic blood pressure increased significantly after cold
      pressor test in both normal (systolic blood pressure from 110+/-6.46 to 119+/
      9.45 mmHg and diastolic blood pressure from 71+/-4.63 to 78+/-6.15 mmHg) and
      prehypertensive group (systolic blood pressure from 122+/-6.75 to 126+/-8.05 mmHg
      and diastolic blood pressure from 79+/-6.78 to 85+/-7.76 mmHg). Maximum recovery
      in both systolic and diastolic blood pressure was observed in 2.5 minutes of
      removal of hand from cold water. Though sharp drop was observed in blood pressure
      at the end of 2.5 minute in both groups of individuals, the recovery in case of
      prehypertensive individual was not sharper. In the present study, significant
      rise in diastolic blood pressure was observed in prehypertensive smoking males.
      Also the difference was significant (p<0.02) in recovery of diastolic blood
      pressure between smoker and non smoker prehypertensive group. Conclusion This
      study suggests that prolonged elevation in blood pressure in response to stress
      in young individual can be used as marker of development of hypertension in
      future. Adopting a healthier lifestyle can help to delay the development of
      hypertension in later life.

PMID- 29336423
TI  - Prevalence of Anatomical Variations of the Sinonasal Region and their
      Relationship with Chronic Rhinosinusitis.
AB  - Background Precise knowledge of anatomic variations of nose and paranasal sinus
      complex is essential for achieving best surgical results during endoscopic sinus
      surgery. Computed tomography is the gold standard investigation for evaluation of
      paranasal sinuses and adjacent structures. Objective To study prevalence of
      anatomical variations of nose, paranasal sinuses and osteomeatal complex and to
      identify a probable association between anatomical variations and chronic
      rhinosinusitis. Method Prospective, analytical study conducted in 218 patients
      with Chronic rhinosinusitis in Department of Radiology, Dhulikhel Hospital,
      Kathmandu University Hospital between January 2015 to January 2016. Volumetric
      axial CT scan was done in 128 slice CT scanner in 3mm thickness from frontal
      sinus to floor of maxillary sinus with thin multiplanar reconstruction.
      Radiological findings were reviewed and obtained data analyzed with SPSS version
      16. Pearson chi square test and Pearson correlation coefficient were used for
      statistical analysis. Result The most common anatomical variation was pneumatized
      agger nasi cells followed by concha bullosa and deviated nasal septum
      respectively. Statistical significance were seen between ipsilateral agger nasi
      cell and frontal sinusitis (p< 0.001), ipsilateral haller cell and concha bullosa
      with maxillary sinusitis (p<0.001) and onodi cell with sphenoid sinusitis
      (p<0.001), However, no obvious statistical correlation was noted between deviated
      nasal septum with ipsilateral maxillary sinusitis. Conclusion Precise knowledge
      of anatomic variations of the paranasal sinuses is important in chronic
      rhinosinusitis to prevent possible complications during surgery. Computed
      tomography is the modality of choice in evaluation of paranasal sinuses and
      adjacent structures.

PMID- 29336425
TI  - Multi-Detector Computed Tomography Evaluation of Normal Appendix.
AB  - Background Appendix is a blind-ended tubular structure arising from caecum, with
      variable intraluminal contents and position. Acute appendicitis is one of the
      common indications for emergency radiological investigation. Objective To assess
      visualization rate, size and position of normal appendix by Computed Tomography
      (CT). Method This cross-sectional observational study was done in 198 individuals
      undergoing abdominal CT without suspicion of acute appendicitis and without any
      pathology localized within right iliac fossa. Axial and coronal reformatted
      images of nonenhanced and contrast enhanced CT of abdomen were evaluated for
      visualization of appendix. Visualized appendices arising from caecum were traced
      and tip localized. Contents within the appendicular lumen were also evaluated and
      maximum transverse diameter of appendix measured. The relationship between
      appendicular diameter, intraluminal content and position with different age
      groups & gender were also derived. Result Visualization rates of appendix were
      90% (93% male and 87% female) in nonenhanced CT and 97% (99.8% male and 95.4%
      female) in enhanced CT. The mean diameter of the appendix was 6.2 +/- 1.16 mm.
      Most common location of the tip of appendix was pelvic position, followed by
      retrocaecal position. Most of the appendices showed intraluminal air. Conclusion
      Multi-Detector Computed Tomography is superior over ultrasonography (USG) in
      detection of appendix. Modifications of CT protocol reduce limitations of CT over
      ultrasound in evaluation of appendix. Ultrasound size criteria for appendicitis
      (>6 mm) is not applicable in CT as normal appendix can measure >6 mm in CT.

PMID- 29336424
TI  - Clinical Profile and Electroencephalogram Findings in Children with Seizure
      Presenting to Dhulikhel Hospital.
AB  - Background Seizure disorder is the most common childhood neurologic condition and
      a major public health concern. Identification of the underlying seizure etiology
      helps to identify appropriate treatment options and the prognosis for the child.
      Objective This study was conducted to investigate the clinical profile, causes
      and electroencephalogram findings in children with seizure presenting to a
      tertiary center in Kavre district. Method This was a hospital based prospective
      study carried out in the Department of Pediatrics, Dhulikhel Hospital, Kavre from
      1st April 2015 to 31st March 2016. Variables collected were demographics,
      clinical presentations, laboratory tests, brain imaging studies,
      electroencephalography, diagnosis and outcome. Result Study included 120 (age 1
      month to 16 years) children attending Dhulikhel Hospital. Majority of the
      patients were male (60.84%). Age at first seizure was less than 5 years in 75.83%
      of children. Seizure was generalized in 62.50%, focal in 31.67% and unclassified
      in 5.83%. Common causes of seizure were - Primary generalized epilepsy (26.66%),
      neurocysticercosis (10%) and hypoxic injury (6.6%) which was diagnosed in the
      perinatal period. Febrile seizure (26.66%) was the most common cause of seizure
      in children between 6 months to 5 years of age. Neurological examination,
      electroencephalography and Computed Tomography were abnormal in 71.66%, 68.92%
      and 58.14% cases respectively. Seizure was controlled by monotherapy in 69.16%
      cases and was resistant in 7.50% of the cases. Conclusion Primary generalized
      epilepsy and febrile seizure were the most common causes of seizures in children
      attending Dhulikhel Hospital. Electroencephalogram findings help to know the
      pattern of neuronal activity. Response to monotherapy was good and valproic acid
      was the most commonly used drug.

PMID- 29336426
TI  - Combination Topical PUVAsol with Methotrexate Versus Methotrexate in the
      Treatment of Palmoplantar Psoriasis.
AB  - Background Non-pustular palmoplantar psoriasis (PPP) is chronic and disabling
      dermatosis. Topical psoralen and solar ultraviolet - A therapy (PUVAsol) is
      efficacious and safe therapy in psoriasis management. Objective To study the
      efficacy and adverse clinical effect profile of topical PUVAsol along with
      methotrexate in PPP. Method This is a prospective, randomized, clinical trial
      conducted among 54 patients with moderate to severe PPP. Patients were grouped
      into two categories. Group I was treated with weekly oral methotrexate only while
      group II had additional soak PUVAsol therapy twice weekly for a total of three
      months. Modified palmoplantar psoriasis area severity index (mPPPASI) score was
      used for quantification of severity. Patients were followed up monthly for the
      efficacy and adverse clinical event profile for 3 months; additionally patients
      were followed up monthly for next three months for assessment of relapse. Result
      The mean age of patients with PPP was found to be 38.7 +/- 13 years and male:
      female ratio was 1.1:1. In comparison to group I patients, statistically
      significant improvement was observed among group II patients in the third month
      follow up (p= 0.039). Fifteen patients (35%) achieved mPPPASI 75 during the
      treatment period. No significant difference was noted among the mPPPASI score
      during relapse assessment. Eleven (29%) patients had evidence of relapse (mPPPASI
      more than 25% of baseline) during follow up period. No statistically significant
      adverse clinical events were noted. Conclusion Topical PUVAsol is an efficacious,
      safe and cost effective modality in moderate to severe PPP. It could be employed
      in rotational or maintenance therapy of psoriasis.

PMID- 29336427
TI  - Congenital Bilateral Coloboma of Upper Eyelid.
AB  - Congenital coloboma of eyelid is a rare anomaly. There is partial or total
      absence of eyelid structures. A seven year male child had coloboma of both the
      upper lids lateral to lacrimal puctum affecting the medial half of lid
      symmetrically with symblepharon in region of defect bilaterally. The study was
      carried out at Maharaja Krushna Chandra Gajpati Medical College Berhampur, Odisha
      in year 2010. Both eyebrows were abnormal. He presented on and off diminution of
      vision, burning sensation, redness and watering from both the eyes on and off. On
      examination high refractive error was detected (visual aquity was 6/18 in
      righteye and 6/24 in left eye). Cornea was dry and opacities were present in both
      the eyes. There was limitation of ocular movement in both sides due to
      symblepharon. Nystagmus was present. The subject did not have any other
      associated anomaly. The birth and family history was normal. This case can be
      surgically treated and earliest management can give good fuctional as well as
      cosmetic results.

PMID- 29336428
TI  - Keratocystic Odontogenic Tumour Mimicking Lateral Periodontal Cyst: A Diagnostic
      Dilemma.
AB  - The Keratocystic Odontogenic Tumor is a developmental cyst derived from the
      enamel organ or from the dental lamina. It is a benign, multicystic, intraosseous
      tumor of odontogenic origin, with a characteristic lining of parakeratinized
      stratified squamous epithelium and has a potential for aggressive, infiltrative
      behavior and recurrence. Keratocystic Odontogenic Tumors have a predilection for
      males and occurs mainly in the second and third decade of life, most commonly in
      the mandible, mostly in the posterior body, the angle and the ascending ramus. It
      extends in the intramedullary space making it difficult to diagnose at an early
      stage. It is regarded as a distinctive entity because of its characteristic
      histology, proliferation kinetics and behavior. Main in 1970 described,
      collateral variant of Keratocystic Odontogenic Tumor, which presents adjacent to
      the roots of the teeth usually in the mandibular premolar region and
      radiologically is indistinguishable from the lateral periodontal cyst and
      gingival cyst.

PMID- 29336429
TI  - Thyroid Isthmus Agenesis in a Patient with Papillary Carcinoma of Thyroid.
AB  - Thyroid gland is the largest of all endocrine glands. It is composed of two
      lobes. These two lobes are joined by an isthmus and this resemble the letter "H".
      A wide range of morphological variations and developmental anomalies of the
      thyroid gland like hypoplasia, ectopy, hemiagenesis, and agenesis have been
      reported in literature. Out of these, the incidence of agenesis of the thyroid
      isthmus is rare, and very few cases have been reported. In our report, 28 year
      old male patient was found with agenesis of thyroid isthmus with papillary
      carcinoma in the right lobe of thyroid. During the operation it was seen that the
      right and left thyroid lobes were independent from each other and isthmus was
      absent. We will present a case of thyroid isthmus agenesis and discuss the
      clinical importance and the incidence of this case.

PMID- 29336430
TI  - Persistent Trophoblastic Disease at Cesarean Scar.
AB  - Pregnancy over the cesarean scar is the rarest cause of ectopic pregnancy and
      development of persistent trophoblastic disease at the scar site is extremely
      rare. A high index of suspicion is needed for early diagnosis and management of
      cesarean scar molar pregnancy. This condition is difficult to diagnose and must
      be considered in the patient with a history of cesarean section who has
      persistent vaginal bleeding or symptoms of pregnancy after suction evacuation.
      Diagnosis can be confirmedby measuring beta Human Chorionic Gonadotropin levels,
      transvaginal ultrasound with doppler flow evaluation. As this is an uncommon
      condition, this case report with conservative non surgical approach will add up
      to its clinical spectrum.

PMID- 29336431
TI  - Anti-PD1 in the wonder-gut-land.
AB  - After the initial success of cancer immunotherapy using immune checkpoint
      blockers, the challenge is to understand why only a minority of patients respond
      to the therapy and to increase the rate of response. Three recent papers now
      report that the gut microbiota modulates the response to anti-PD1 therapy in
      patients with epithelial cancers or melanoma.

PMID- 29336432
TI  - Increased Mortality Rates With Prolonged Corticosteroid Therapy When Compared
      With Antitumor Necrosis Factor-alpha-Directed Therapy for Inflammatory Bowel
      Disease.
AB  - OBJECTIVES: Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory
      bowel diseases (IBD) that compromise quality of life and may increase mortality.
      This study compared the mortality risk with prolonged corticosteroid use vs.
      antitumor necrosis factor-alpha (anti-TNF) drugs in IBD. METHODS: A retrospective
      cohort study was conducted among Medicaid and Medicare beneficiaries from 2001 to
      2013 with IBD prescribed either >3,000 mg of prednisone or equivalent within a 12
      month period or new initiation of anti-TNF therapy, each treated as time-updating
      exposures. The primary outcome was all-cause mortality. Secondary outcomes
      included common causes of death. Marginal structural models were used to
      determine odds ratios (ORs) and 95% confidence intervals (CIs) for anti-TNF use
      relative to corticosteroids. RESULTS: Among patients with CD, 7,694 entered the
      cohort as prolonged corticosteroid users and 1,879 as new anti-TNF users. Among
      patients with UC, 3,224 and 459 entered the cohort as prolonged CS users and new
      anti-TNF users, respectively. The risk of death was statistically significantly
      lower in patients treated with anti-TNF therapy for CD (21.4 vs. 30.1 per 1,000
      person-years, OR 0.78, 0.65-0.93) but not for UC (23.0 vs. 30.9 per 1,000 person
      years, OR 0.87, 0.63-1.22). Among the CD cohort, anti-TNF therapy was also
      associated with lower rates of major adverse cardiovascular events (OR 0.68, 0.55
      0.85) and hip fracture (OR 0.54, 0.34-0.83). CONCLUSIONS: Compared with prolonged
      corticosteroid exposure, anti-TNF drug use was associated with reduced mortality
      in patients with CD that may be explained by lower rates of major adverse
      cardiovascular events and hip fracture.

PMID- 29336433
TI  - Eosinophilic Esophagitis: Relationship of Subepithelial Eosinophilic Inflammation
      With Epithelial Histology, Endoscopy, Blood Eosinophils, and Symptoms.
AB  - OBJECTIVES: For technical reasons, the histologic characterization of
      eosinophilic esophagitis (EoE)-specific alterations is almost exclusively based
      on those found in the esophageal epithelium, whereas little is known about
      subepithelial abnormalities. In this study, we aimed to systematically assess the
      nature of subepithelial histologic alterations, and analyze their relationship
      with epithelial histologic findings, endoscopic features, and symptoms. METHODS:
      Adult patients with established EoE diagnosis were prospectively included during
      a yearly follow-up visit. Patients underwent assessment of clinical, endoscopic,
      and histologic disease activity using EoE-specific scores. RESULTS: We included
      200 EoE patients (mean age 43.5+/-15.7 years, 74% males) with a median peak count
      of 36 intraepithelial eosinophils/hpf (IQR 14-84). The following histologic
      features were identified in the subepithelial layer: eosinophilic infiltration
      (median peak count of 20 eosinophils/hpf (IQR 10-51)), eosinophil degranulation
      (43%), fibrosis (82%), and lymphoid follicles (56%). Peak intraepithelial
      eosinophil counts were higher, identical, and lower when compared to the
      subepithelial layer in 62.5%, 7%, and 30.5% of patients, respectively. Anti
      eosinophilic treatment at inclusion did not influence the relation between
      subepithelial and epithelial peak eosinophil counts. Subepithelial histologic
      activity correlated with epithelial histologic activity (rho 0.331, P<0.001),
      endoscopic severity (rho 0.208, P=0.003), and symptom severity (rho 0.179,
      P=0.011). Forty percent (21/52) of patients with <15 intraepithelial
      eosinophils/hpf had subepithelial peak counts of >=15/hpf. CONCLUSIONS: There is
      a significant but modest correlation between subepithelial histologic activity
      and epithelial histologic activity, endoscopic severity, and symptom severity.
      The long-term clinical impact of assessing subepithelial alterations in EoE needs
      to be further elucidated.

PMID- 29336435
TI  - Cardiac regeneration in 2017: Novel paradigms in the fight against heart failure.

PMID- 29336436
TI  - Dyslipidaemias in 2017: Atherogenic lipoproteins as treatment targets.

PMID- 29336437
TI  - Ge12{Fe(CO)3}8(MU-I)4: a germanium-iron cluster with Ge4, Ge2 and Ge units.
AB  - The germanium-iron cluster Ge12{Fe(CO)3}8(MU-I)4 was prepared by reacting GeI4
      and Fe2(CO)9 in [BMIm]Cl/AlCl3 as ionic liquid (BMIm: 1-butyl-3
      methylimidazolium). The cluster contains a Ge12Fe8 metal core consisting of a
      central Ge4 rectangle, two Ge2 pairs, and four single Ge atoms. These Ge units
      are interconnected by Fe atoms to a real Ge-Fe cluster. According to DFT
      calculations, Hund's localization criterion is fulfilled for the whole cluster if
      we assume three different atomic charges on the Ge4, Ge2, and Ge units.

PMID- 29336434
TI  - ACG Clinical Guideline: Alcoholic Liver Disease.
AB  - Alcoholic liver disease (ALD) comprises a clinical-histologic spectrum including
      fatty liver, alcoholic hepatitis (AH), and cirrhosis with its complications. Most
      patients are diagnosed at advanced stages and data on the prevalence and profile
      of patients with early disease are limited. Diagnosis of ALD requires
      documentation of chronic heavy alcohol use and exclusion of other causes of liver
      disease. Prolonged abstinence is the most effective strategy to prevent disease
      progression. AH presents with rapid onset or worsening of jaundice, and in severe
      cases may transition to acute on chronic liver failure when the risk for
      mortality, depending on the number of extra-hepatic organ failures, may be as
      high as 20-50% at 1 month. Corticosteroids provide short-term survival benefit in
      about half of treated patients with severe AH and long-term mortality is related
      to severity of underlying liver disease and is dependent on abstinence from
      alcohol. General measures in patients hospitalized with ALD include inpatient
      management of liver disease complications, management of alcohol withdrawal
      syndrome, surveillance for infections and early effective antibiotic therapy,
      nutritional supplementation, and treatment of the underlying alcohol-use
      disorder. Liver transplantation, a definitive treatment option in patients with
      advanced alcoholic cirrhosis, may also be considered in selected patients with AH
      cases, who do not respond to medical therapy. There is a clinical unmet need to
      develop more effective and safer therapies for patients with ALD.

PMID- 29336438
TI  - Zein-derived peptides as nanocarriers to increase the water solubility and
      stability of lutein.
AB  - Zein and its derived peptides have been used as nanocarriers for bioactive
      components. Lutein, as well as other xanthophylls, are characterized by blue
      light filtering and anti-oxidant properties. However, lutein is unstable and has
      low water solubility, poor absorption, and low bioavailability. In order to
      protect lutein from oxidative degradation, and to enhance its solubility and
      dispersibility, stability and bioactivity, lutein-loaded zein nanoparticles (LLZ
      NP) and zein-derived peptide nanoparticles (LLZ-PEP-NP) were prepared by the
      solvent diffusion method. Compared to LLZ-NP, LLZ-PEP-NP possessed good
      physicochemical properties, including particle size, polydispersity index, zeta
      potential, entrapment efficiency and in vitro stability. Specifically,
      transmission electron microscopy (TEM) images showed that LLZ-PEP-NP had a
      spherical form with a nanometric size and lutein was efficiently loaded into zein
      derived peptides through self-assembly. Dynamic light scattering (DLS) results
      demonstrated that LLZ-PEP-NP had a narrow size distribution in the range of 200
      300 nm and a decreased zeta potential compared to that of LLZ-NP. The lutein
      entrapment efficiency (EE%) of LLZ-NP and LLZ-PEP-NP was more than 85%, while LUT
      PEP-NP showed higher lutein entrapment efficiency because of the better capacity
      of peptides bound with lutein. Nanoencapsulation of lutein into LLZ-PEP-NP
      resulted in a significantly higher solubility compared to nanoencapsulation of
      lutein into LLZ-NP and free lutein. The stabilities of lutein in zein-derived
      peptide nanoparticles in simulated gastric fluid (SGF) and simulated intestinal
      fluid (SIF) were improved. These results suggest that zein-derived peptides have
      the potential to be used as nanocarriers to enhance the solubility and stability
      of lutein, which can further improve its bioavailability.

PMID- 29336439
TI  - Tailoring a nanostructured plasmonic absorber for high efficiency surface
      assisted laser desorption/ionization.
AB  - The surface-assisted laser desorption/ionization (SALDI) effect is investigated
      on Au plated anodized aluminum oxide (Au/AAO) thin films, a new type of low-cost
      broadband plasmonic absorber, which has attracted a lot of attention recently.
      Mass spectrometry (MS) measurements show that the ionization efficiency of Au/AAO
      substrates can be significantly improved (*30 fold) by simply tuning the size of
      nanopores in Au/AAOs. This leads to a signal-to-noise ratio of 394, which is 4
      times better than the result obtained using the conventional matrix-assisted
      laser desorption/ionization (MALDI)-MS technique. Experimental and theoretical
      studies show that the dramatic improvement is caused by the pore-size-dependent
      optical and thermal properties of Au/AAOs. It provides a simple yet effective
      strategy for designing and building high performance plasmonic SALDI substrates.

PMID- 29336440
TI  - Manganese/cobalt-catalyzed oxidative C(sp3)-H/C(sp3)-H coupling: a route to alpha
      tertiary beta-arylethylamines.
AB  - Reported herein is an oxidative coupling reaction of an alpha-C(sp3)-H bond of
      amine with a benzylic C(sp3)-H bond through Mn or Co catalysis to provide diverse
      collections of alpha-tertiary beta-arylethylamines. This protocol features an
      easily installed and removable coordinating activation group, a wide scope of
      substrates, low-cost metal catalysts, easily available starting materials and
      synthetic simplicity.

PMID- 29336441
TI  - A high pressure study of calmodulin-ligand interactions using small-angle X-ray
      and elastic incoherent neutron scattering.
AB  - Calmodulin (CaM) is a Ca2+ sensor and mediates Ca2+ signaling through binding of
      numerous target ligands. The binding of ligands by Ca2+-saturated CaM (holo-CaM)
      is governed by attractive hydrophobic and electrostatic interactions that are
      weakened under high pressure in aqueous solutions. Moreover, the potential
      formation of void volumes upon ligand binding creates a further source of
      pressure sensitivity. Hence, high pressure is a suitable thermodynamic variable
      to probe protein-ligand interactions. In this study, we compare the binding of
      two different ligands to holo-CaM as a function of pressure by using X-ray and
      neutron scattering techniques. The two ligands are the farnesylated hypervariable
      region (HVR) of the K-Ras4B protein, which is a natural binding partner of holo
      CaM, and the antagonist trifluoperazine (TFP), which is known to inhibit holo-CaM
      activity. From small-angle X-ray scattering experiments performed up to 3000 bar,
      we observe a pressure-induced partial unfolding of the free holo-CaM in the
      absence of ligands, where the two lobes of the dumbbell-shaped protein are
      slightly swelled. In contrast, upon binding TFP, holo-CaM forms a closed globular
      conformation, which is pressure stable at least up to 3000 bar. The HVR of K
      Ras4B shows a different binding behavior, and the data suggest the dissociation
      of the holo-CaM/HVR complex under high pressure, probably due to a less dense
      protein contact of the HVR as compared to TFP. The elastic incoherent neutron
      scattering experiments corroborate these findings. Below 2000 bar, pressure
      induces enhanced atomic fluctuations in both holo-CaM/ligand complexes, but those
      of the holo-CaM/HVR complex seem to be larger. Thus, the inhibition of holo-CaM
      by TFP is supported by a low-volume ligand binding, albeit this is not associated
      with a rigidification of the complex structure on the sub-ns A-scale.

PMID- 29336442
TI  - Ambient chemical fixation of CO2 using a highly efficient heterometallic helicate
      catalyst system.
AB  - Two novel heptanuclear 3d-4f helicates have been synthesized and characterized.
      The helicates act as catalysts and show high catalytic activity for the coupling
      of CO2 and epoxides to obtain cyclic carbonates with a wide substrate scope at
      ambient temperature and pressure.

PMID- 29336443
TI  - Actuating and memorizing bilayer hydrogels for a self-deformed shape memory
      function.
AB  - A general strategy for fabricating a double layer self-deformed shape memory
      hydrogel which includes a thermo-responsive actuating layer and a pH-responsive
      memorizing layer is presented. Compared with traditional shape memory polymer
      systems, the temporary shape of the hydrogel could be generated by a thermo
      responsive actuating layer upon the trigger of heat without the need for an
      external force, which could be further memorized by the pH-responsive memorizing
      layer.

PMID- 29336444
TI  - The structural diversity of C-rich DNA aggregates: unusual self-assembly of
      beetle-like nanostructures.
AB  - We studied the ability of oligonucleotides CnT25 (n = 2, 5, 7, 9, 12, 25) to form
      an intermolecular i-motif using circular dichroism, ultra-violet spectroscopy,
      nuclear magnetic resonance, high-resolution atomic force microscopy, high
      performance liquid chromatography, and molecular dynamics simulations. The
      arrangement of single-stranded oligonucleotides in multimer i-motifs was very
      unusual: C-tracts of different oligonucleotides followed each other consecutively
      in order to fold into a closed intermolecular i-motif core with minimal loops
      (one cytidine in a loop spanning over a minor groove, three cytidines in a loop
      over a major groove); intact T-tracts protruded from predefined loci allowing
      visualization of beetle-like nanostructures by atomic force microscopy. The same
      structures were formed from analogous biotinylated oligonucleotides demonstrating
      one of the potential applications of such structures as carriers of multiple
      functional groups. Our findings open up possibilities for the rational design of
      pH-sensitive DNA aggregates and evaluation of the efficiency of their assembly.

PMID- 29336445
TI  - Single Pd atomic catalyst on Mo2CO2 monolayer (MXene): unusual activity for CO
      oxidation by trimolecular Eley-Rideal mechanism.
AB  - The geometric stability, electronic structure and catalytic properties of a
      single Pd atom deposited on a pristine Mo2CO2 monolayer and a defective Mo2CO2
      monolayer with an oxygen vacancy (denoted as Pd/OV-Mo2CO2) are systematically
      investigated through density functional theory. We find that the oxygen vacancy
      (OV) can stabilize the single Pd atom and make the Pd/OV-Mo2CO2 system an
      excellent mono-dispersed atomic catalyst. The Pd dopant serves as an active
      center which makes the intermediates react productively around it. Three reaction
      mechanisms are considered for CO oxidation to test the catalytic activity of
      Pd/OV-Mo2CO2, which exhibits high activity for CO oxidation via a tri-molecular
      Eley-Rideal (TER) mechanism with a rate-limiting energy barrier of 0.49 eV. The
      pre-adsorbed CO molecules on the Pd dopant could transfer electrons to the O2
      2pi* orbitals, which would promote O2 molecule activation and induce O-O bond
      scission. This work demonstrates that the defective monolayer MXene may serve as
      a promising sort of support to fabricate single atomic catalysts (SACs) for CO
      oxidation or other reactions, agreeing well with the experimental reports, which
      opens up a new avenue for the design and fabrication of SACs of MXene-based
      materials.

PMID- 29336446
TI  - An elimination/Heck coupling/allylation cascade reaction: synthesis of 2,3
      dihydrobenzofurans from allenoate adducts.
AB  - A highly regio- and stereoselective Pd-catalyzed cascade reaction of allenoate
      adducts has been developed. Various allenoate adducts of phosphine-catalyzed
      addition of allenoates are found to be efficient substrates for the preparation
      of 2,3-dihydrobenzofuran. It is the first example of allenoate adducts used as
      ideal and practical precursors of hard-to-get functionalized 1,3-butadienes for
      heterocycle synthesis.

PMID- 29336447
TI  - Synthesis of indolizine derivatives containing eight-membered rings via a gold
      catalyzed two-fold hydroarylation of diynes.
AB  - A gold-catalyzed method for the construction of indolizines with eight-membered
      rings has been developed. The reaction proceeded through a two-fold
      hydroarylation with indole or pyrrole derivatives containing a 1,6-diyne using a
      tri(1-adamantyl)phosphine gold complex as the catalyst, affording 1,8
      disubstituted indolizines in moderate to good yields in DCE at 80  degrees C. The
      potential usefulness of these indolizines as blue or green OLEDs has been also
      disclosed.

PMID- 29336448
TI  - Determination of derived volumetric properties and heat capacities at high
      pressures using two density scaling based equations of state. Application to
      dipentaerythritol hexa(3,5,5-trimethylhexanoate).
AB  - Reliable equations of state (EoS) together with heat capacities at atmospheric
      pressure make it possible to determine properties such as the isobaric thermal
      expansivity, compressibility, both isothermal and isentropic, high pressure
      isobaric heat capacities or speed of sound. In this work, we analysed the
      reliability of two density scaling based EoS, Power-Law Density Scaling (PLDS)
      and General Density Scaling (GDS), and the Tammann-Tait EoS to determine these
      quantities. For this aim, dipentaerythritol hexa(3,5,5-trimethylhexanoate),
      diPEiC9, was chosen because it has been recently proposed as a candidate to fill
      the gap of reference fluids suitable for high pressure viscometer calibration or
      their verification. New experimental densities measured between (283.15 and
      398.15) K at pressures up to 70 MPa together with isobaric heat capacities
      between (282.93 and 399.92) K and thermal conductivities between (283 and 333) K
      at 0.1 MPa of diPEiC9 are reported. Literature relative volumes up to 400 MPa for
      this compound were also used. The three EoSs give rise to coherent values of the
      above properties. The most difficult property to describe is isobaric thermal
      expansivity for which the isobaric curves can present minima and/or maxima and
      the isotherm curves can cross at different pressures. The loci of the maxima of
      the isobaric thermal expansivity in p-T diagrams of the GDS and PLDS EoSs are
      very close.

PMID- 29336450
TI  - Lithium diamidodihydridoaluminates: bimetallic cooperativity in catalytic
      hydroboration and metallation applications.
AB  - Cooperativity between the Li and Al centres is implicated in catalytic
      hydroboration reactions of aldehydes and ketones with pinacolborane via
      heteroleptic lithium diamidodihydridoaluminates. In addition to implementing
      hydroalumination, these versatile heteroleptic ates can also perform as amido
      bases as illustrated with an acidic triazole.

PMID- 29336449
TI  - pH-Dependent cooperativity and existence of a dry molten globule in the folding
      of a miniprotein BBL.
AB  - Solution pH plays an important role in protein dynamics, stability, and folding;
      however, detailed mechanisms remain poorly understood. Here we use continuous
      constant pH molecular dynamics in explicit solvent with pH replica exchange to
      describe the pH profile of the folding cooperativity of a miniprotein BBL, which
      has drawn intense debate in the past. Our data reconciled the two opposing
      hypotheses (downhill vs. two-state) and uncovered a sparsely populated unfolding
      intermediate. As pH is lowered from 7 to 5, the folding barrier vanishes. As pH
      continues to decrease, the unfolding barrier lowers and denaturation is triggered
      by the protonation of Asp162, consistent with experimental evidence.
      Interestingly, unfolding proceeded via an intermediate, with intact secondary
      structure and a compact, unlocked hydrophobic core shielded from solvent, lending
      support to the recent hypothesis of a universal dry molten globule in protein
      folding. Our work demonstrates that constant pH molecular dynamics is a unique
      tool for testing this and other hypotheses to advance the knowledge in protein
      dynamics, stability, and folding.

PMID- 29336451
TI  - The uptake, retention and clearance of drug-loaded dendrimer nanoparticles in
      astrocytes - electrophysiological quantification.
AB  - Nanoparticle-based drug delivery systems may impose risks to patients due to
      potential toxicity associated with a lack of clearance from cells or prolonged
      carrier-cell retention. This work evaluates vesicular cell uptake, retention and
      the possible transfer of endocytosed methylprednisolone-loaded
      carboxymethylchitosan/poly(amidoamine) dendrimer nanoparticles (NPs) into
      secretory vesicles of rat cultured astrocytes. The cells were incubated with NPs
      and unitary vesicle fusions/fissions with the plasma membrane were monitored
      employing high-resolution membrane capacitance measurements. In the NP-treated
      cells the frequency of unitary exocytotic events was significantly increased. The
      presence of NPs also induces an increase in the size of exocytotic vesicles
      interacting with the plasma membrane, which exhibit transient fusion with
      prolonged fusion pore dwell-time. Live-cell confocal imaging revealed that once
      NPs internalize into endocytotic compartments they remain in the cell for 7 days,
      although a significant proportion of these merge with secretory vesicles destined
      for exocytosis. Co-localization studies show the route of clearance of NPs from
      cells via the exocytotic pathway. These findings bring new insight into the
      understanding of the intracellular trafficking and biological interactions of
      drug-loaded dendrimer NPs targeting astrocytes.

PMID- 29336452
TI  - Resonant scattering of green light enabled by Ag@TiO2 and its application in a
      green light projection screen.
AB  - The ability to selectively scatter green light is essential for an RGB
      transparent projection display, and this can be achieved by a silver-core,
      titania-shell nanostructure (Ag@TiO2), based on the metallic nanoparticle's
      localized surface plasmon resonance. The ability to selectively scatter green
      light is shown in a theoretical design, in which structural optimization is
      included, and is then experimentally verified by characterization of a
      transparent film produced by dispersing such nanoparticles in a polymer matrix. A
      visual assessesment indicates that a high-quality green image can be clearly
      displayed on the transparent film. For completeness, a theoretical design for
      selective scattering of red light based on Ag@TiO2 is also shown.

PMID- 29336453
TI  - Semimetallic carbon honeycombs: new three-dimensional graphene allotropes with
      Dirac cones.
AB  - Classic two-dimensional (2D) graphene possesses outstanding properties due to
      Dirac cone structures. When scaling up to three-dimensional (3D) structures,
      their high porosity and large surface-area-to-volume ratio made them have more
      promising engineering perspectives. However, the currently synthesized and
      density-functional-theory-predicted 3D graphene structures, termed as carbon
      honeycombs (CHCs), are metallic. Herein, we propose new families of stable
      semimetallic CHC structures, which have lower energies than the previous
      experimentally reported structure and they would be realized experimentally.
      Results from density functional theory (DFT) and tight binding (TB) model showed
      that multiple Dirac cones with massless Dirac Fermions are present in both
      pristine and strained CHCs. Dirac cones in pristine CHCs originated from
      interactions between sp2-hybridized carbon atoms along the zigzag direction
      (denoted as C, i = alpha, beta,...), while strain-induced direction-dependent
      Dirac cones primarily stemmed from interactions (i) between the two C atoms
      bonded to a selected sp3-hybridized carbon atom or (ii) between C and C (alpha
      carbon atoms at the armchair direction) atoms. The largest Fermi velocity
      achieved is 1.204 * 106 m s-1, which is approximately 44.7% larger than that of
      graphene. These results open up a new direction in carbon-based 3D porous
      materials and these findings provide significant insights on numerous
      applications, ranging from nanoelectronics and nanomechanics to gas and liquid
      separations.

PMID- 29336455
TI  - 5'-Vitamin B12 derivatives suitable for bioconjugation via the amide bond.
AB  - Vitamin B12 is an attractive candidate for a drug or an imaging-agent carrier
      into cells, due to its dietary uptake and well established transport through
      glycoproteins. Utilization of this system requires an appropriate
      functionalization of vitamin B12 that both allows for the conjugation of
      therapeutics and does not interrupt its recognition by transport proteins.
      Modifications at the 5'-position on the ribose moiety are among a few approaches
      which meet the criteria. In this article we present vitamin B12 derivatives
      bearing either the amino or the carboxylic group at the 5'-position. The presence
      of these functional groups enables conjugation of biologically important
      molecules to vitamin B12via the amide bond. The established method is not only
      limited to organic media but also works in an aqueous environment, giving the
      desired products in very good yields.

PMID- 29336454
TI  - High temporal resolution delayed analysis of clinical microdialysate streams.
AB  - This paper presents the use of tubing to store clinical microdialysis samples for
      delayed analysis with high temporal resolution, offering an alternative to
      traditional discrete offline microdialysis sampling. Samples stored in this way
      were found to be stable for up to 72 days at -80  degrees C. Examples of how this
      methodology can be applied to glucose and lactate measurement in a wide range of
      in vivo monitoring experiments are presented. This paper presents a general
      model, which allows for an informed choice of tubing parameters for a given
      storage time and flow rate avoiding high back pressure, which would otherwise
      cause the microdialysis probe to leak, while maximising temporal resolution.

PMID- 29336461
TI  - New di-anchoring A-pi-D-pi-A configured organic chromophores for DSSC
      application: sensitization and co-sensitization studies.
AB  - Herein, we report the design and synthesis of three new un-symmetrical metal-free
      carbazole based organic dyes, E1-3 with A-pi-D-pi-A architecture, as effective di
      anchoring sensitizers in DSSCs. The new entities comprise carbazole as a donor
      scaffold connected to three different units, viz. cyano acetic acid, 2,4
      thiazolidinedione and barbituric acid as acceptor/anchoring units via vinylene
      and phenylene as pi-spacers at 3- and 6-positions of the carbazole ring,
      respectively. Photophysical, electrochemical and theoretical studies were carried
      out in order to assess their feasibility as active sensitizers. Furthermore,
      their photoelectrochemical performances and charge transport properties in
      fabricated DSSCs were evaluated. The results revealed that the device fabricated
      with the E1 sensitizer displayed the highest PCE of 2.38% among the three dyes.
      Its JSC, VOC, and IPCE values were found to be 6.36 mA cm-2, 0.599 V, and 57%,
      respectively. Its enhanced performance is attributed to the presence of a highly
      electron withdrawing cyano acetic acid unit on either side of the carbazole core
      through appropriate pi-spacers. Interestingly, the DFT study indicated that the
      electron cloud of the LUMO level has been shifted significantly towards the 2
      cyano phenyl acrylic acid connected at the 6th position of the carbazole ring,
      when compared to the cyano acrylic acid linked at position 3, confirming
      efficient charge separation in E1. The assigned lifetimes of E1-3 obtained from
      EIS studies were found to be in accordance with experimentally obtained
      photovoltaic parameters. Furthermore, E1-3, when co-sensitized with NCSU-10
      sensitizer in DSSCs, displayed higher VOC values, but lower PCE values than that
      of NCSU-10.

PMID- 29336462
TI  - Cascaded photo-potential in a carbon dot-hematite system driving overall water
      splitting under visible light.
AB  - Hematite is an earth-abundant and ubiquitous semiconductor with a suitable
      bandgap of 2.1 eV for solar water splitting. Unfortunately, it suffers from a low
      conduction band position compared to the H+/H2 potential and typically an
      external bias has to be applied. Here, we demonstrate carbon dot-hematite (CD
      Fe2O3) nanocomposites as photocatalysts for visible-light-driven overall water
      splitting without any external bias or scavenger. Notably, the CD-Fe2O3
      nanocomposites (carbon dots, 5 wt%) show a hydrogen evolution rate of 0.390 MUmol
      h-1 and an oxygen evolution rate of 0.225 MUmol h-1 under visible light
      illumination. In our system, carbon dots have been well coupled with hematite and
      are detected to generate a photo-induced potential. This photo-potential can be
      combined with hematite to meet the requirement for overall water splitting. In
      addition, carbon dots can significantly improve the charge separation efficiency.
      Our finding may greatly enhance the practical application of hematite for solar
      water splitting.

PMID- 29336463
TI  - Protein corona in drug delivery for multimodal cancer therapy in vivo.
AB  - The protein corona is inevitably formed on nanoparticles (NPs) when they are
      introduced in vivo and has been associated with a reduction in targeting yield,
      immune recognition and rapid blood clearance, leading to poor tumor accumulation.
      We have recently shown that it is possible to exploit the protein corona for drug
      delivery by exploiting it for loading and triggering the release of a
      photosensitizer Chlorin e6 (Ce6) for simultaneous photodynamic (PDT) and
      photothermal therapy (PTT) in vitro. Here, we extended our previous in vitro
      studies to evaluate its effectiveness in vivo. Specifically, we pre-formed the
      protein corona from mouse serum (MS) around gold nanorods (NRs) and loaded it
      with Ce6 to form NR-MS-Ce6. The intravenous delivery of NR-MS-Ce6 at a dose of 10
      mg kg-1 Au loaded with 9.63 MUg kg-1 Ce6 into tumor-bearing NCr nude mice
      resulted in their tumor accumulation reaching a peak concentration of 560.3 MUg
      Au per kg tissue (0.0752% dose) within 6 h post-injection. Subsequent localized
      laser irradiation of the xenograft tumor resulted in a significant tumor
      temperature increase of 16.85  degrees C within 20 min. Combined with the
      simultaneous reactive oxygen species (ROS) production by Ce6 for PDT, complete
      tumor regression was achieved within 19 days with no tumor regrowth up to 31
      days. Similar to other NPs, significant gold accumulation was observed in the
      major reticuloendothelial system (RES) organs, particularly the liver and spleen,
      although no acute toxicity was observed histologically 31 days post-treatment.
      Our results demonstrated for the first time an in vivo application of the protein
      corona around NPs in the loading and delivery of drugs in small animals. The ease
      of drug loading and the biocompatibility of the endogenous serum-based protein
      corona could make it useful for drug delivery and therapeutic applications
      instead of merely being considered as a biological artefact to be eliminated.

PMID- 29336464
TI  - Edge orientation dependent nanoscale friction.
AB  - Nanoscale friction is generally found to be a function of the contact area.
      However, little is known whether and how it is dependent on the contact area
      shape. In this study, based on molecular dynamics (MD) simulations about a
      rectangular graphene flake sliding on a diamond-supported graphene substrate, we
      show that the friction between the flake and the substrate is significantly
      dependent on the flake edge oriented perpendicular to the sliding direction, but
      less dependent on the edge along the sliding direction. As a result, the friction
      between the flake and the substrate is closely related to the aspect ratio of the
      flake. We propose a novel nanoscale friction formula for the translational motion
      of a rectangular slider. The simulation data fit the formula well and the effect
      of the aspect ratio on nanoscale friction can thus be efficiently captured. We
      discuss also the origin of the edge orientation dependent nanoscale friction. The
      present findings provide not only a preliminary evaluation of the contact area
      shape dependent nanoscale friction, but also a quite important guide for modeling
      the friction properties of nanodevices based on two-dimensional (2D) materials.

PMID- 29336465
TI  - Breast cancer stem-like cells are sensitized to tamoxifen induction of self
      renewal inhibition with enforced Let-7c dependent on Wnt blocking.
AB  - Let-7 microRNAs have been reported to have tumor suppressive functions; however,
      the effect of Let-7 when used in combination with chemotherapies is uncertain,
      but may have potential for use in clinical practice. In this study, we used RT
      qPCR, western blot analysis, cell proliferation assay, flow cytometry analysis,
      immunohistochemistry (IHC) staining, luciferase assays, cell sorting analysis and
      xenografted tumor model to explore the role of Let-7 in the chemotherapy
      sensitivity of breast cancer stem cells. The findings of the current study
      indicated that Let-7 enhances the effects of endocrine therapy potentially by
      regulating the self-renewal of cancer stem cells. Let-7c increased the anticancer
      functions of tamoxifen and reduced the ratio of cancer stem-like cells (CSCs),
      sensitizing cells to therapy-induced repression in an estrogen receptor (ER)
      dependent manner. Notably, Let-7 decreased the tumor formation ability of
      estrogen-treated breast CSCs in vivo and suppressed Wnt signaling, which further
      consolidated the previously hypothesis that Let-7 decreases the self-renewal
      ability, contributing to reduced tumor formation ability of stem cells. The
      suppressive effects exerted by Let-7 on stem-like cells involved Let-7c/ER/Wnt
      signaling, and the functions of Let-7c exerted with tamoxifen were dependent on
      ER. Taken together, the findings identified a biochemical and functional link
      between Let-7 and endocrine therapy in breast CSCs, which may facilitate clinical
      treatment in the future using delivery of suppressive Let-7.

PMID- 29336466
TI  - Magnolol protects against ischemic-reperfusion brain damage following oxygen
      glucose deprivation and transient focal cerebral ischemia.
AB  - In the present study, the neuroprotective potential of magnolol against ischemia
      reperfusion brain injury was examined via in vivo and in vitro experiments.
      Magnolol exhibited strong radical scavenging and antioxidant activity, and
      significantly inhibited the production of interleukin-6, tumor necrosis factor-a
      and nitrite/nitrate (NOX) in lipopolysaccharide-stimulated BV2 and RAW 264.7
      cells when applied at concentrations of 10 and 50 uM, respectively. Magnolol (100
      uM) also significantly attenuated oxygen-glucose deprivation-induced damage in
      neonatal rat hippocampal slice cultures, when administered up to 4 h following
      the insult. In a rat model of stable ischemia, compared with a vehicle-treated
      ischemic control, pretreatment with magnolol (0.01-1 mg/kg, intravenously)
      significantly reduced brain infarction following ischemic stroke, and post
      treatment with magnolol (1 mg/kg) remained effective and significantly reduced
      infarction when administered 2 h following the onset of ischemia. Additionally,
      magnolol (0.3 and 1 mg/kg) significantly reduced the accumulation of superoxide
      anions at the border zones of infarction and reduced oxidative damage in the
      ischemic brain. This was assessed by measuring the levels of NOX, malondialdehyde
      and myeloperoxidase, the ratio of glutathione/oxidized glutathione and the
      immunoreactions of 8-hydroxy-2'-deoxyguanosine and 4-hydroxynonenal. Thus,
      magnolol was revealed to protect against ischemia-reperfusion brain damage. This
      may be partly attributed to its antioxidant, radical scavenging and anti
      inflammatory effects.

PMID- 29336467
TI  - NOX4/ROS mediate ethanol-induced apoptosis via MAPK signal pathway in L-02 cells.
AB  - The aim of the present study was to assess the molecular mechanism of ethanol
      induced oxidative stress-mediated apoptosis in L-02 liver cells in order to
      elucidate novel pathways associated with alcoholic liver disease. L-02 cells were
      treated with 400 mM ethanol with or without inhibitors. The cell viability was
      measured by an MTT assay. Cell apoptosis was assessed by flow cytometry and a
      single-stranded DNA (ssDNA) assay. Intracellular reactive oxygen species (ROS)
      production of L-02 cells was determined using the 2',7'-dichlorofluorescein
      diacetate dye. The protein expression of c-Jun N-terminal kinase (JNK),
      phosphorylated (p)-JNK, P38, p-P38, NADPH oxidase (NOX)1, NOX4, p22phox, B-cell
      lymphoma 2 (Bcl-2) and Bcl-2-associated X protein were measured by western blot
      analysis. The mRNA expression of NOX1, NOX4 and p22phox was measured by reverse
      transcription polymerase chain reaction analysis. The results indicated that
      after treatment with various concentrations of ethanol for the indicated
      durations, L-02 cells were displayed a significant decrease in cell viability in
      a dose-and time-dependent manner. Ethanol-induced apoptosis and cell death of L
      02 cells was accompanied by the generation of ROS, elevated expression of NOX, as
      well as phosphorylation of JNK and P-38. In addition, increased expression of Bcl
      2 was induced by 400 mM ethanol. Furthermore, treatment with NOX inhibitor
      attenuated the ethanol-induced a decrease in cell viability, and an increase in
      apoptosis and Bcl-2 expression. In conclusion, ethanol induced apoptosis in the L
      02 hepatocyte cell line via generation of ROS and elevated expression of NOX4.
      This indicated that activation of JNK and p38 in the mitogen-activated protein
      kinase pathway promotes apoptosis in L-02 cells.

PMID- 29336468
TI  - Increased expression of sterol regulatory element binding protein-2 alleviates
      autophagic dysfunction in NAFLD.
AB  - Sterol regulatory element binding protein-2 (SREBP-2) is an important
      transcription factor in lipid homeostasis. A previous study showed that SREBP-2
      also activated autophagic genes during cell-sterol depletion. Alterations in
      autophagy are reported to be involved in the pathogenesis of nonalcoholic fatty
      liver disease (NAFLD). However, whether the regulation of SREBP-2 restores
      dysfunctional autophagy in hepatocytes during NAFLD remains to be elucidated. In
      the present study, a steatosis model was established with palmitic acid (PA)
      treatment at the indicated times and concentrations. Autophagosomes in
      hepatocytes were visualized by confocal microscopy after transfection with a
      tandem GFP-mCherry-LC3 construct. Autophagy-associated protein levels were
      analyzed by western blot analysis. Loss- and gain-of-function studies were
      performed to examine the role of SREBP-2 in the regulation of hepatocyte
      autophagy. It was demonstrated that PA induced autophagy and enhanced autophagic
      flux at the early stage, whereas prolonged treatment with PA resulted in
      dysfunction of autophagy in the PA-induced steatotic hepatocytes. In addition,
      different cellular models presented with differing dysfunctional autophagy in
      response to fatty acid overload. It was also confirmed that SREBP-2 regulated
      autophagy-related gene expression in hepatocytes, and it was shown that the
      overexpression of SREBP-2 increased the expression of autophagy-related genes,
      but did not affect the inhibition of the autophagic flux in lipid-overloaded HL
      7702 cells. By contrast, increased SREBP-2 partly restored the inhibited
      autophagic activity in lipid-overloaded hepatoma HepG2 cells. Taken together, the
      present study demonstrated that autophagic function was impaired in lipid
      overloaded human hepatocytes, and the differential effect of PA on autophagy was
      associated with the duration of PA and the cell type. Under these conditions, the
      overexpression of SREBP-2 alleviated the inhibited autophagic activity rather
      than the inhibition of autophagic flux. Consequently, the results indicated that
      restoration of autophagy dysfunction via the regulation of SREBP-2 may be a
      potential therapeutic target for the treatment of NAFLD.

PMID- 29336469
TI  - Transcriptional regulation of HIV-1 host factor COMMD1 by the Sp family.
AB  - Copper metabolism Murr1 domain containing 1 (COMMD1) has multiple functions in
      the regulation of protein stability at the plasma membrane and in the cytoplasm.
      However, the regulation of COMMD1 transcriptional has remained to be elucidated.
      In the present study, the 5'-flanking region (-1,192/+83 bp) of the human COMMD1
      gene was cloned. It was observed that the COMMD1 promoter region contains GC-rich
      region that has 7 putative Sp1-binding sites via in silico analysis. The proximal
      promoter region at -289/+83 bp was required for COMMD1 basal promoter activity by
      deletion constructs of COMMD1 promoter. Moreover, Sp1 inhibitor, mithramycin A,
      suppressed basal COMMD1 promoter activity. The Sp1-binding site (-11/-1 bp) in
      the proximal promoter region was a critical site for COMMD1 gene regulation by
      Sp1 and Sp3. Sp1 upregulated COMMD1 promoter activity, whereas Sp3 suppressed it.
      Endogenous Sp1 and Sp3 bound to the proximal promoter region of COMMD1. Taken
      together, Sp1 constitutively regulates the basal expression of the COMMD1 gene in
      human epithelial cell lines.

PMID- 29336470
TI  - TNF-alpha induces Drp1-mediated mitochondrial fragmentation during inflammatory
      cardiomyocyte injury.
AB  - Dynamin-related peptide 1 (Drpl)-mediated mitochondrial fission is an important
      process associated with cardiac dysfunction under different pathological
      conditions. The aim of the present study was to investigate the expression of
      Drpl during inflammatory myocardial injury. Sprague-Dawley rats were treated
      intraperitoneally with lipopolysaccharides (LPS). Furthermore, cultured H9C2
      cardiomyocytes were treated with LPS, interleukin-6 (IL-6) and tumor necrosis
      factor-alpha (TNF-alpha). Total and mitochondrial proteins were isolated from the
      heart tissue of rats and from the H9C2 cardiomyocytes. Expression levels of Drp1
      and RhoA were analyzed by western blotting. Mitochondrial morphology was
      determined using confocal laser microscopy. The levels of mitochondrial Drp1 and
      phosphorylated-Drp1 (p-Drp1) Ser616 were revealed to be increased in rats 6 h
      after injection with LPS (5, 10 or 20 mg/kg). Furthermore, treatment with LPS and
      IL-6 did not demonstrate a significant effect on the expression of total and
      mitochondrial Drp1 in H9C2 cardiomyocytes in vitro; however, treatment with TNF
      alpha (20 ng/ml) significantly enhanced the levels of mitochondrial Drp1 and p
      Drp1 Ser616. Following TNF-alpha treatment, the expression of Ras homolog gene
      family member A (RhoA) was also revealed to increase. Treatment with both Y-27632
      and fasudil, [Rho kinase (ROCK) inhibitors], was demonstrated to attenuate the
      otherwise TNF-alpha-induced increase in p-Drp1 Ser616 and mitochondrial Drp1. In
      addition, it was revealed that Y-27632 and fasudil may also attenuate the TNF
      alpha-induced increase in mitochondrial fragmentation and cell viability.
      Therefore, the findings of the present study suggest that TNF-alpha is the
      predominant inducer of Drp1 S616 phosphorylation during sepsis. The results of
      the present study also suggest that the RhoA/ROCK pathway may be involved in the
      phosphorylation and mitochondrial translocation of Drp1, which leads to
      mitochondrial fragmentation.

PMID- 29336471
TI  - Neuroprotective effects of p53/microRNA-22 regulate inflammation and apoptosis in
      subarachnoid hemorrhage.
AB  - The present study aimed to investigate whether the neuroprotective effects of
      p53/microRNA-22 regulate inflammation and apoptosis in subarachnoid hemorrhage
      (SAH). In a mouse model of SAH, microRNA-22 expression was upregulated. In
      addition, downregulation of microRNA-22 in HEB cells increased the mRNA
      expression levels of interleukin (IL)-6, induced cysteine rich angiogenic inducer
      61 (Cyr61) expression, and suppressed the protein expression levels of B-cell
      lymphoma 2-associated X protein (Bax) and caspase-3 activity. Treatment with the
      p53 inhibitor, pifithrin-alpha, suppressed p53 protein expression, increased IL-6
      mRNA expression, decreased microRNA-22 expression, Bax protein expression and
      caspase-3 activity, and induced Cyr61 expression in mice with SAH. Furthermore,
      p53 expression was knocked down using p53 small interfering RNA, which suppressed
      microRNA-22 expression and increased IL-6 mRNA expression, inhibited Bax protein
      expression and caspase-3 activity, and induced Cyr61 expression in HEB cells. The
      present study demonstrated that the neuroprotective effects of p53/microRNA-22
      may regulate inflammation and apoptosis in SAH. Reverse transcription
      quantitative polymerase chain reaction (qPCR) was used to analyze the expression
      of microRNA-22, western blot analysis was used to analyze the protein expression
      of Bax and Cyr61.

PMID- 29336473
TI  - Usefulness of identifying G-protein-coupled receptor dimers for diagnosis and
      therapy of neurodegenerative diseases and of gliomas.
AB  - Immunochemical detection of G-protein-coupled receptors (GPCRs) in cells and
      tissues was a technical challenge for years. After the discovery of formation of
      GPCR dimers/trimers/tetramers in transfected cells, a most recent challenge has
      been to confirm receptor-receptor interactions in natural sources. The occurrence
      of dimers or higher order oligomers is important from a therapeutic point of
      view, mainly because their physiology/pharmacology is different from those of
      individual receptors. On the one hand, pathophysiological factors need to count
      more on GPCR dimers than on individual receptors. On the other hand, the
      expression of dimers, trimers, etc. may change in pathological conditions and/or
      along the course of a disease. This review will focus on G-protein-coupled
      receptor dimers, on how to detect them by novel histological techniques and on
      how the detection may be used in diagnosis and therapy of ailments of the central
      nervous system, for instance in neurodegenerative diseases and gliomas.

PMID- 29336472
TI  - Baicalin increases hair follicle development by increasing canonical Wnt/beta
      catenin signaling and activating dermal papillar cells in mice.
AB  - Baicalin is a traditional Chinese herbal medicine commonly used for hair loss,
      the precise molecular mechanism of which is unknown. In the present study, the
      mechanism of baicalin was investigated via the topical application of baicalin to
      reconstituted hair follicles on mice dorsa and evaluating the effect on canonical
      Wnt/beta-catenin signaling in the hair follicles and the activity of dermal
      papillar cells. The results indicate that baicalin stimulates the expression of
      Wnt3a, Wnt5a, frizzled 7 and disheveled 2 whilst inhibiting the Axin/casein
      kinase 1alpha/adenomatous polyposis coli/glycogen synthase kinase 3beta
      degradation complex, leading to accumulation of beta-catenin and activation of
      Wnt/beta-catenin signaling. In addition, baicalin was observed to increase the
      alkaline phosphatase levels in dermal papillar cells, a process which was
      dependent on Wnt pathway activation. Given its non-toxicity and ease of topical
      application, baicalin represents a promising treatment for alopecia and other
      forms of hair loss. Further studies of baicalin using human hair follicle
      transplants are warranted in preparation for future clinical use.

PMID- 29336474
TI  - Exposure to violence, teacher support, and school delay amongst adolescents in
      South Africa.
AB  - BACKGROUND: Many adolescents in South Africa are exposed to multiple types of
      violence, socio-economic disadvantage, and low-quality education: all risk
      factors for educational outcomes including school delay (grade enrolment below
      that which is age-appropriate). Supportive teacher-student relationships are
      known to be associated with improved academic outcomes in high-income contexts.
      AIMS: To investigate whether the academic and emotional support provided by
      teachers can protect against school delay for adolescents exposed to multiple
      types of violence and socio-economic disadvantage in South Africa. SAMPLE: High
      risk sample of 503 adolescents aged 10-18 exposed to multiple types of violence
      and socio-economic disadvantage at home, in school, and in their communities.
      METHODS: Multilevel aggregated structural equation modelling was applied to
      pre/post-RCT data. This investigated whether associations between adolescent
      exposure to violence and school delay could be lessened by having teachers who
      were academically and/or emotionally supportive. RESULTS: More frequent exposure
      to 'poly-violence' and receiving more emotional support from teachers were
      independently associated with greater school delay. On the contrary, higher
      academic support from teachers was associated with lower school delay. Neither
      academic nor emotional teacher support was found to moderate the relationship
      between more frequent exposure to 'poly-violence' and an increased risk of
      adolescent school delay. CONCLUSION: Adolescents' academic support from teachers
      is low in poorly resourced school contexts in South Africa. School-based
      secondary prevention programmes assisting teachers with more training and
      academic support in deprived contexts have potential to reduce the impact of
      violence and socio-economic disadvantage on adolescents' school delay.

PMID- 29336475
TI  - Exosomes originating from MSCs stimulated with TGF-beta and IFN-gamma promote
      Treg differentiation.
AB  - Mesenchymal stem cells (MSCs) have been approved as a cellular drug for the
      treatment of a variety of immune-related diseases by the government of many
      countries'. Previous investigations, including ours, have shown that exosomes
      secreted by MSCs (MSC-ex) are one of the main factors responsible for the
      therapeutic effect of MSCs. However, the immune modulation activities and the
      contents of MSC-ex derived from cells under different incubation conditions
      differ dramatically. Therefore, the optimal way to ensure effectiveness is by
      identifying and preparing MSC-ex with confirmed potent immunosuppressive
      activity. The aim of this study was to investigate and analyze the composition
      and function of MSC-ex secreted by MSCs stimulated by different cytokines to
      obtain exosomes with more potent immunosuppressive activity. To achieve this aim,
      umbilical cord-derived MSCs were treated with PBS, TGF-beta, IFN-gamma, or TGF
      beta plus IFN-gamma for 72 hr. Then, exosomes were isolated from the culture
      supernatants. Common exosome markers, such as CD9, CD63, and CD81, were detected
      and analyzed by FCM. At the same time, the TGF-beta, IFN-gamma, IDO, and IL-10
      content in exosomes was detected, and the influence of exosmes from defferent
      groups on the induction of mononuclear cell transformation into Tregs was
      analyzed via FCM. Our results show that the TGF-beta combined with IFN-gamma
      exosome group more effectively promoted the transformation of mononuclear cells
      to Tregs, and the analysis showed that IDO may play an important role. This study
      might provide a novel strategy to treat GVHD as well as other immune-associated
      disorders.

PMID- 29336476
TI  - Drivers and demographic consequences of seasonal mass changes in an alpine
      ungulate.
AB  - We know little about the determinants and demographic consequences of the marked
      seasonal mass changes exhibited by many northern and alpine mammals. We analysed
      43 years of data on individual winter mass loss (the difference between mass in
      early June and mass in mid-September the previous year) and summer mass gain (the
      difference between mass in mid-September and in early June of the same year) in
      adult bighorn sheep (Ovis canadensis). We calculated relative seasonal mass
      change as a proportion of individual body mass at the start of each season. We
      first examined the effects of weather and population density on relative changes
      in body mass. We then assessed the consequences of relative seasonal mass changes
      on reproduction. Mean April-May temperature was the main driver of relative
      seasonal mass changes: warm springs reduced both relative winter mass loss and
      summer mass gain of both sexes, likely partially due to a trade-off between
      growth rate of plants and duration of access to high-quality forage. Because
      these effects cancelled each other, spring temperature did not influence mass in
      mid-September. Mothers that lost relatively more mass during the winter had lambs
      that gained less mass during summer, likely because these females allocated fewer
      resources to lactation. Winter survival of lambs increased with their summer mass
      gain. In males, relative mass loss during winter, which includes the rut, did not
      influence the probability of siring at least one lamb, possibly indicating that
      greater mating effort did not necessarily translate into greater reproductive
      success. Our findings improve our understanding of how weather influences
      recruitment and underline the importance of cryptic mechanisms behind the effects
      of climate change on demographic traits.

PMID- 29336477
TI  - Intraoperative adverse events associated with extremely preterm cesarean
      deliveries.
AB  - INTRODUCTION: At the same time as survival is increasing among premature babies
      born before 26 weeks of gestation, the rates of cesarean deliveries before 26
      weeks is also rising. Our purpose was to compare the frequency of intraoperative
      adverse events during cesarean deliveries in two gestational age groups: 24-25
      weeks and 26-27 weeks. MATERIAL AND METHODS: This single-center retrospective
      cohort study included all women with cesarean deliveries performed before 28+0
      weeks from 2007 through 2015. It compared the frequency of intraoperative adverse
      events between two groups: those at 24-25 weeks of gestation and at 26-27 weeks.
      Intraoperative adverse events were a classical incision, transplacental incision,
      difficulty in fetal extraction (explicitly mentioned in the surgical report),
      postpartum hemorrhage (>=500 mL of blood loss), and injury to internal organs. A
      composite outcome including at least one of these events enabled us to analyze
      the risk factors for intraoperative adverse events with univariate and
      multivariable analysis. Stratified analyses by the indication for the cesarean
      were performed. RESULTS: We compared 74 cesarean deliveries at 24-25 weeks of
      gestation and 214 at 26-27 weeks. Intraoperative adverse events occurred at
      higher rates in the 24-25-week group (63.5 vs. 30.8%, p < 0.001). After
      adjustment for confounding factors, this group remained at significantly higher
      risk of intraoperative adverse events [adjusted odds ratio 5.04 (2.67-9.50)],
      even after stratification by indication for the cesarean. CONCLUSION: These
      results should help obstetricians and women making decisions about cesarean
      deliveries at these extremely low gestational ages.

PMID- 29336478
TI  - Apelin-13 treatment enhances the stability of atherosclerotic plaques.
AB  - BACKGROUND: Apelin is an endogenous peptidergic system which modulates
      cardiovascular function. Recent studies pointed out a fundamental contribution of
      apelin on atherosclerosis development; however, such reports revealed
      contradictory data, and to date, it is difficult to accurately define a
      beneficial or deleterious role. To better understand apelin function on
      atherosclerosis, we aimed to investigate apelin-13 treatment effects on
      atherosclerotic plaques composition. DESIGN: Apolipoprotein E gene-deleted mice
      were fed on Western-type diet for 11 weeks. Atherosclerotic plaque formation was
      induced in the carotid artery by a shear stress modifier device, which exposes
      the same vessel to distinct patterns of shear stress enabling the formation of
      plaques with different composition. Mice were treated with apelin-13 (2 mg kg-1
      day-1 ) or vehicle for the last 3 weeks. RESULTS: Apelin-13 treatment did not
      alter the lipid content of low shear stress- and oscillatory shear stress-induced
      plaques in the carotid. However, apelin-13 greatly ameliorated plaque stability
      by increasing intraplaque collagen content and reducing MMP-9 expression.
      Furthermore, apelin-13 decreased the infiltration of inflammatory cells
      (neutrophil and macrophage) and intraplaque reactive oxygen species content.
      Interestingly, apelin-13 treatment reduced total cholesterol, LDL levels and free
      fatty acid serum levels, while HDL, triglycerides serum levels were not
      significantly changed. CONCLUSIONS: Apelin-13 treatment for 3 weeks did not alter
      the lesion size, but it significantly enhanced the stable phenotype of
      atherosclerotic plaques and improved serum lipid profile. These results indicate
      that activation of apelin system decreases plaque vulnerability.

PMID- 29336479
TI  - Inhibition of glycolytic metabolism in glioblastoma cells by Pt3glc combinated
      with PI3K inhibitor via SIRT3-mediated mitochondrial and PI3K/Akt-MAPK pathway.
AB  - Glioblastoma multiforme (GBM) is the most malignant and aggressive glioma with
      abnormal expression of genes that mediate glycolytic metabolism and tumor cell
      growth. Petunidin-3-O- glucoside (Pt3glc) is a kind of anthocyanin in the red
      grape and derived beverages, representing the most common naturally occurring
      anthocyanins with a reduced incidence of cancer and heart diseases. In this
      study, whether Pt3glc could effectively regulate glycolysis to inhibit GBM cell
      was investigated by using the DBTRG-05MG cell lines. Notably, Pt3glc displayed
      potent anti-proliferative activity and significantly changed the protein levels
      related to both glycolytic metabolism and GBM cell survival. The expression of
      the pro-apoptotic protein Bax was increased with concomitant reduction on the
      levels of the anti-apoptotic protein Bcl-2 and caspase-3 activity. Furthermore,
      the levels of survival signaling proteins, such as Akt and p-Akt (Scr473), ERK
      and phospho-ERK, were significantly decreased by Pt3glc in combination with the
      PI3K inhibitor of LY294002. Most importantly, the levels of SIRT3 and
      phosphorylated p53 were also down-regulation, indicating that Pt3glc combinated
      with PI3K inhibitor could induced GBM cell death may act via the SIRT3/p53
      mediated mitochondrial and PI3K/Akt-ERK pathways. Our findings thus provide
      rational evidence that the combination of Pt3glc with PI3K inhibitor, which
      target alternative pathways in GBM cells, may be a useful adjuvant therapy in
      glioblastoma treatment. This article is protected by copyright. All rights
      reserved.

PMID- 29336480
TI  - Species co-occurrence networks: Can they reveal trophic and non-trophic
      interactions in ecological communities?
AB  - Co-occurrence methods are increasingly utilized in ecology to infer networks of
      species interactions where detailed knowledge based on empirical studies is
      difficult to obtain. Their use is particularly common, but not restricted to,
      microbial networks constructed from metagenomic analyses. In this study, we test
      the efficacy of this procedure by comparing an inferred network constructed using
      spatially intensive co-occurrence data from the rocky intertidal zone in central
      Chile to a well-resolved, empirically based, species interaction network from the
      same region. We evaluated the overlap in the information provided by each network
      and the extent to which there is a bias for co-occurrence data to better detect
      known trophic or non-trophic, positive or negative interactions. We found a poor
      correspondence between the co-occurrence network and the known species
      interactions with overall sensitivity (probability of true link detection) equal
      to 0.469, and specificity (true non-interaction) equal to 0.527. The ability to
      detect interactions varied with interaction type. Positive non-trophic
      interactions such as commensalism and facilitation were detected at the highest
      rates. These results demonstrate that co-occurrence networks do not represent
      classical ecological networks in which interactions are defined by direct
      observations or experimental manipulations. Co-occurrence networks provide
      information about the joint spatial effects of environmental conditions,
      recruitment, and, to some extent, biotic interactions, and among the latter, they
      tend to better detect niche-expanding positive non-trophic interactions.
      Detection of links (sensitivity or specificity) was not higher for well-known
      intertidal keystone species than for the rest of consumers in the community.
      Thus, as observed in previous empirical and theoretical studies, patterns of
      interactions in co-occurrence networks must be interpreted with caution,
      especially when extending interaction-based ecological theory to interpret
      network variability and stability. Co-occurrence networks may be particularly
      valuable for analysis of community dynamics that blends interactions and
      environment, rather than pairwise interactions alone.

PMID- 29336481
TI  - The "unguarded-X" and the genetic architecture of lifespan: Inbreeding results in
      a potentially maladaptive sex-specific reduction of female lifespan in Drosophila
      melanogaster.
AB  - Sex differences in ageing and lifespan are ubiquitous in nature. The "unguarded
      X" hypothesis (UXh) suggests they may be partly due to the expression of
      recessive mutations in the hemizygous sex chromosomes of the heterogametic sex,
      which could help explain sex-specific ageing in a broad array of taxa. A
      prediction central to the UX hypothesis is that inbreeding will decrease the
      lifespan of the homogametic sex more than the heterogametic sex, because only in
      the former does inbreeding increase the expression of recessive deleterious
      mutations. In this study, we test this prediction by examining the effects of
      inbreeding on the lifespan and fitness of male and female Drosophila melanogaster
      across different social environments. We found that, across social environments,
      inbreeding resulted in a greater reduction of female than male lifespan, and that
      inbreeding effects on fitness did not seem to counterbalance sex-specific effects
      on lifespan, suggesting the former are maladaptative. Inter- and intra-sexual
      correlation analyses also allowed us to identify evidence of an underlying joint
      genetic architecture for inbreeding effects on lifespan. We discuss these results
      in light of the UXh and other alternative explanations, and suggest that more
      attention should be paid to the possibility that the "unguarded-X" may play an
      important role in the evolution of sex-specific lifespan.

PMID- 29336482
TI  - Litter removal in a tropical rain forest reduces fine root biomass and production
      but litter addition has few effects.
AB  - Many old-growth lowland tropical rain forests are potentially nutrient limited,
      and it has long been thought that many such forests maintain growth by recycling
      nutrients from decomposing litter. We investigated this by continuously removing
      (for 10 yr) freshly fallen litter from five (45 m * 45 m) plots, adding it to
      five other plots, there were five controls. From monthly measures over 1 yr we
      show that litter removal caused lower: fine root (<=2 mm diameter) standing mass,
      fine root standing length, fine root length production and fine root length
      survivorship. Litter addition did not significantly change fine root mass or
      length or production. Nutrient concentrations in fine roots in litter removal
      plots were lower than those in controls for nitrogen (N), calcium (Ca) and
      magnesium (Mg), concentrations in fine roots in litter addition plots were higher
      for N and Ca. Chronic litter removal has resulted in reduced forest growth due to
      lack of nutrients, probably nitrogen. Conversely, long-term litter addition has
      had fewer effects.

PMID- 29336483
TI  - Glucose metabolism during in vitro maturation of mouse oocytes: An study using
      RNA interference.
AB  - In previous studies on glucose metabolism during in vitro maturation, intact
      cumulus-oocyte complexes (COCs) were treated with enzyme inhibitors/activators.
      Because inhibitors/activators may have non-specificity and/or toxicity, and
      culture of COCs cannot differentiate whether glucose metabolism of cumulus cells
      (CCs) or that of the oocyte supports oocyte maturation, results from the previous
      studies must be verified by silencing genes in either CCs or cumulus-denuded
      oocytes (DOs). In this study, RNAi was adopted to specify the effects of glucose
      metabolism in CCs or DOs on oocyte maturation. Although silencing either
      glyceraldehyde 3-phosphate dehydrogenase (GAPDH) or glucose-6-phosphate
      dehydrogenase (G6PD) genes in CCs significantly decreased competence of the
      cocultured DOs, silencing G6PD impaired competence to a greater extent. While
      silencing G6PD or GAPDH of CCs decreased glutathione and ATP contents of
      cocultured DOs to similar extents, silencing G6PD increased oxidative stress as
      well. Analysis on metabolite contents and oxidative stress index and culture of
      DOs in medium conditioned with gene-silenced CCs indicated that CCs supported
      oocyte maturation by releasing glucose metabolites. Silencing mitochondrial
      pyruvate carrier 1 or NADH dehydrogenase (ubiquintone) flavoprotein 1 of DOs
      significantly impaired their maturation. The results have unequivocally confirmed
      that CCs promote oocyte maturation by releasing glucose metabolites from both
      pentose phosphate pathway (PPP) and glycolysis. Pyruvate is transferred into DOs
      by mitochondrial pyruvate carrier (MPC) and utilized through mitochondrial
      electron transport to support maturation.

PMID- 29336484
TI  - Epigenetic regulation of megakaryocytic and erythroid differentiation by PHF2
      histone demethylase.
AB  - Plant homeodomain finger 2 (PHF2) is a JmjC family histone demethylase that
      demethylates H3K9me2, a repressive gene marker. PHF2 was found to play a role in
      the differentiation of several tissue types such as osteoblast and adipocyte
      differentiation. We report here that PHF2 plays a role in the epigenetic
      regulation of megakaryocytic (MK) and erythroid differentiation. We investigated
      PHF2 expression during MK and erythroid differentiation in K562 and human CD34+
      progenitor (hCD34+ ) cells. Our data demonstrate that PHF2 expression is down
      regulated during megakaryopoiesis and erythropoiesis. PHF2 has a negative role in
      MK and erythroid differentiation of K562 cells; knockdown of PHF2 promotes MK and
      erythroid differentiation of hCD34+ cells. Similarly, we found that p53
      expression is also down-regulated during MK and erythroid differentiation, which
      parallels PHF2 expression. PHF2 binds to the p53 promoter and regulates the
      expression of p53 by demethylating H3K9me2 in the promoter region of p53. Taken
      together, our data show that PHF2 is a negative epigenetic regulator of MK and
      erythroid differentiation, and that one of the pathways through which PHF2
      affects MK and erythroid differentiation is via regulation of p53 expression.

PMID- 29336485
TI  - A multimodal microcharacterisation of trace-element zonation and crystallographic
      orientation in natural cassiterite by combining cathodoluminescence, EBSD, EPMA
      and contribution of confocal Raman-in-SEM imaging.
AB  - In cassiterite, tin is associated with metals (titanium, niobium, tantalum,
      indium, tungsten, iron, manganese, mercury). Knowledge of mineral chemistry and
      trace-element distribution is essential for: the understanding of ore formation,
      the exploration phase, the feasibility of ore treatment, and disposal/treatment
      of tailings after the exploitation phase. However, the availability of analytical
      methods make these characterisations difficult. We present a multitechnical
      approach to chemical and structural data that includes scanning electron
      microscopy (SEM)-based imaging and microanalysis techniques such as: secondary
      and backscattered electrons, cathodoluminescence (CL), electron probe
      microanalyser (EPMA), electron backscattered diffraction (EBSD) and confocal
      Raman-imaging integrated in a SEM (RISE). The presented results show the
      complementarity of the used analytical techniques. SEM, CL, EBSD, EPMA provide
      information from the interaction of an electron beam with minerals, leading to
      atomistic information about their composition, whereas RISE, Raman spectroscopy
      and imaging completes the studies with information about molecular vibrations,
      which are sensitive to structural modifications of the minerals. The correlation
      of Raman bands with the presence/absence of Nb, Ta, Fe (heterovalent
      substitution) and Ti (homovalent substitution) is established at a submicrometric
      scale. Combination of the different techniques makes it possible to establish a
      direct link between chemical and crystallographic data of cassiterite.

PMID- 29336486
TI  - Preventing post-traumatic stress disorder following childbirth and traumatic
      birth experiences: a systematic review.
AB  - INTRODUCTION: Between 9 and 44% of women experience giving birth as traumatic,
      and 3% of women develop a post-traumatic stress disorder following childbirth.
      Knowledge on risk factors is abundant, but studies on treatment are limited. This
      study aimed to present an overview of means to prevent traumatic birth
      experiences and childbirth-related post-traumatic stress disorder. MATERIAL AND
      METHODS: Major databases [Cochrane; Embase; PsycINFO; PubMed (Medline)] were
      searched using combinations of the key words and their synonyms. RESULTS: After
      screening titles and abstracts and reading 135 full-text articles, 13 studies
      were included. All evaluated secondary prevention, and none primary prevention.
      Interventions included debriefing, structured psychological interventions,
      expressive writing interventions, encouraging skin-to-skin contact with healthy
      newborns immediately postpartum and holding or seeing the newborn after
      stillbirth. The large heterogeneity of study characteristics precluded pooling of
      data. The writing interventions to express feelings appeared to be effective in
      prevention. A psychological intervention including elements of exposure and
      psycho-education seemed to lead to fewer post-traumatic stress disorder symptoms
      in women who delivered via emergency cesarean section. CONCLUSIONS: No research
      has been done on primary prevention of traumatic childbirth. Research on
      secondary prevention of traumatic childbirth and post-traumatic stress disorder
      following delivery provides insufficient evidence that the described
      interventions are effective in unselected groups of women. In certain subgroups,
      results are inhomogeneous.

PMID- 29336487
TI  - Mig6 reduces inflammatory mediators production by regulating the activation of
      EGFR in LPS-induced endotoxemia.
AB  - Epithelial growth factor receptor (EGFR), a tyrosine kinase receptor, plays a
      critical role in lipopolysaccharide (LPS)-induced endotoxemia. Meanwhile, EGFR
      signaling is regulated by multiple feedback regulators, including mitogen
      inducible gene 6 protein (Mig6). However, as an EGFR regulator, the role of Mig6
      in endotoxemia is still remained unknown. Here, we reported for the first time
      that LPS treatment increased the expression of Mig6 and this effect could be
      inhibited by EGFR inhibitor, PD168393 or erlotinib. Furthermore, knocking down of
      Mig6 expression led to increased EGFR activation and inflammatory mediators (TNF
      alpha, il-1beta) production in response to LPS treatment. On the other hand, the
      increased EGFR activation and TNF-alpha or il-1beta production in LPS treatment
      could be inhibited by Mig6 overexpression. Besides, in LPS-induced endotoxemia,
      ERK1/2 and p-38 activation required Mig6. All these results indicated that Mig6
      regulates the production of inflammatory mediators (TNF-alpha, il-1beta) through
      inhibiting the over activation of EGFR, which in turn inhibit MAPKs signaling
      (ERK1/2, p-38). These finding suggested that Mig6 may be a novel potential target
      for controlling the over inflammatory response in endotoxemia.

PMID- 29336489
TI  - Executive summary of the methods report for 'The EAACI/GA2 LEN/EDF/WAO Guideline
      for the Definition, Classification, Diagnosis and Management of Urticaria. The
      2017 Revision and Update'.

PMID- 29336488
TI  - Neonatal Ethanol Exposure Causes Behavioral Deficits in Young Mice.
AB  - BACKGROUND: Fetal ethanol (EtOH) exposure can damage the developing central
      nervous system and lead to cognitive and behavioral deficits, known as fetal
      alcohol spectrum disorders (FASD). EtOH exposure to mouse pups during early
      neonatal development was used as a model of EtOH exposure that overlaps the human
      third-trimester "brain growth spurt"-a model that has been widely used to study
      FASD in rats. METHODS: C57BL/6 male and female mice were exposed to EtOH (4
      g/kg/d) on postnatal days (PD) 4 to 10 by oral intubation. Intubated and
      nontreated controls were also included. Behavioral testing of the offspring,
      including open field, elevated plus maze, and Morris water maze, was performed on
      PD 20 to 45. RESULTS: EtOH exposure during PD 4 to 10 resulted in hyperactivity
      and deficits in learning and memory in young mice with no apparent sex
      differences. CONCLUSIONS: Based on these data, this neonatal intubation mouse
      model may be useful for future mechanistic and genetic studies of FASD and for
      screening of novel therapeutic agents.

PMID- 29336490
TI  - Progress towards a methodology for high throughput 3D reconstruction of soot
      nanoparticles via electron tomography.
AB  - The aim of this work is to make progress towards the development of 3D
      reconstruction as a legitimate alternative to traditional 2D characterization of
      soot. Time constraints are the greatest opposition to its implementation, as
      currently reconstruction of a single soot particle takes around 5-6 h to
      complete. As such, the accuracy and detail gains are currently insufficient to
      challenge 2D characterization of a representative sample (e.g. 200 particles).
      This work is a consideration of the optimization of the steps included within the
      computational reconstruction and manual segmentation of soot particles. Our
      optimal process reduced the time required by over 70% in comparison to a typical
      procedure, whilst producing models with no appreciable decrease in quality.

PMID- 29336491
TI  - Effect of sex steroid hormone fluctuations in the pathophysiology of male-retinal
      pigment epithelial cells.
AB  - Gender-based differences may influence the occurrence of several ocular
      conditions suggesting the possibility that fluctuations in sex steroid
      homeostasis may have direct effects on the eye physiology. Here, we evaluated the
      effect of sex steroid hormone fluctuations in male retinal pigment epithelial
      cells, RPEs (ARPE-19). To mimic hormonal fluctuations occurring during aging, we
      exposed ARPE-19 to acute, prolonged or chronic estradiol, and progesterone
      challenges. We found that chronic estradiol treatment promotes a remarkable
      necrosis of RPE cells, and does not affect pRb2/p130 or PAI-2 sub-cellular
      localization. In contrast, chronic progesterone exposure induces nuclear
      subcellular rearrangement of pRb2/p130, co-immunolocalization of pRb2/p130 with
      PAI-2, and accumulation of cells in G2/M phase, which is accompanied by a
      remarkable reduction of necrosis in favour of apoptosis activation. This study
      has a high clinical significance since it considers sex steroid fluctuations as
      inducers of milieu change in the retina able to influence pathological situations
      occurring with aging in non-reproductive systems such as the eye. Exogenous
      administration of physiologically significant amounts of sex hormones for long
      periods of time is a common clinical practice for transgender patients seeking
      sex reassignment. In particular, our study offers the unique opportunity to
      unravel the effects of sex hormones, not only in determining gender differences
      but also in affecting the physiology of non-reproductive systems, such as the
      eye, in the underserved transgender community.

PMID- 29336492
TI  - Joint effects of chlorpyrifos and mancozeb on the terrestrial isopod
      Porcellionides pruinosus: A multiple biomarker approach.
AB  - The exposure to pesticides by nontarget soil biota has long been regarded as a
      serious downside of modern agricultural regimes and the subject of heated debate.
      Of utmost relevance is the exposure to pesticide mixtures because their effects
      have been shown to not necessarily reflect the individual toxicity of their
      components, and even the simple addition of effects may lead to consequences not
      clearly anticipated. In the present study, a multiple biomarker approach was
      employed to identify the mechanistic and time effects underlying several single
      and mixture treatments of chlorpyrifos (CPF) and mancozeb (MCZ) in juveniles and
      adults of the terrestrial isopod Porcellionides pruinosus. The effects of the
      individual pesticides and the mixtures at recommended doses were mostly
      transitory under these controlled conditions and one-pulse exposure. Whereas
      imbalances were identified on detoxification and oxidative stress-related
      enzymes, the isopods generally showed the ability to recover through the end of
      the experiment. However, juveniles displayed greater vulnerability than adults.
      Most of the differences between life stages occurred in energy-related parameters
      where distinct performances and stress-handling behaviors were observed,
      suggesting higher metabolic costs to juveniles. Our results stress that
      understanding the time dependence of the underlying mechanisms governing the
      joint effects of the pesticides can help in assessing and anticipating the
      effects of the pesticide mixtures. Moreover, we emphasize the importance of
      taking life stage-related differences into consideration when evaluating the
      environmental risks of pesticides and pesticide mixtures. Environ Toxicol Chem
      2018;37:1446-1457. (c) 2018 SETAC.

PMID- 29336494
TI  - Conditional neuromodulation of neurogenic detrusor overactivity using transrectal
      stimulation in patients with spinal cord injury: A proof of principle study.
      Knight SL, Edirisinghe N, Leaker B, Susser J, Craggs MD, Neurourol Urodyn. 2017
      Jun 30.

PMID- 29336493
TI  - N-Terminal Cu-Binding Motifs (Xxx-Zzz-His, Xxx-His) and Their Derivatives:
      Chemistry, Biology and Medicinal Applications.
AB  - Peptides and proteins with N-terminal amino acid sequences NH2 -Xxx-His (XH) and
      NH2 -Xxx-Zzz-His (XZH) form well-established high-affinity CuII -complexes. Key
      examples are Asp-Ala-His (in serum albumin) and Gly-His-Lys, the wound healing
      factor. This opens a straightforward way to add a high-affinity CuII -binding
      site to almost any peptide or protein, by chemical or recombinant approaches.
      Thus, these motifs, NH2 -Xxx-Zzz-His in particular, have been used to equip
      peptides and proteins with a multitude of functions based on the redox activity
      of Cu, including nuclease, protease, glycosidase, or oxygen activation
      properties, useful in anticancer or antimicrobial drugs. More recent research
      suggests novel biological functions, mainly based on the redox inertness of CuII
      in XZH, like PET imaging (with 64 Cu), chelation therapies (for instance in
      Alzheimer's disease and other types of neurodegeneration), antioxidant units, Cu
      transporters and activation of biological functions by strong CuII binding. This
      Review gives an overview of the chemical properties of Cu-XH and -XZH motifs and
      discusses the pros and cons of the vastly different biological applications, and
      how they could be improved depending on the application.

PMID- 29336495
TI  - Acute toxicity of 6 neonicotinoid insecticides to freshwater invertebrates.
AB  - Neonicotinoids are a group of insecticides commonly used in agriculture. Due to
      their high water solubility, neonicotinoids can be transported to surface waters
      and have the potential to be toxic to aquatic life. The present study assessed
      and compared the acute (48- or 96-h) toxicity of 6 neonicotinoids (acetamiprid,
      clothianidin, dinotefuran, imidacloprid, thiacloprid, and thiamethoxam) to 21
      laboratory-cultured and field-collected aquatic invertebrates spanning 10 aquatic
      arthropod orders. Test conditions mimicked species' habitat, with lentic taxa
      exposed under static conditions, and lotic taxa exposed under recirculating
      systems. Median lethal concentrations (LC50s) and median effect concentrations
      (EC50s; immobility) were calculated and used to construct separate lethal- and
      immobilization-derived species sensitivity distributions for each neonicotinoid,
      from which 5th percentile hazard concentrations (HC5s) were calculated. The
      results showed that the most sensitive invertebrates were insects from the orders
      Ephemeroptera (Neocloeon triangulifer) and Diptera (Chironomus dilutus), whereas
      cladocerans (Daphnia magna, Ceriodaphnia dubia) were the least sensitive. The
      HC5s were compared with neonicotinoid environmental concentrations from Ontario
      (Canada) monitoring studies. For all neonicotinoids except imidacloprid, the
      resulting hazard quotients indicated little to no hazard in terms of acute
      toxicity to aquatic communities in Ontario freshwater streams. For the
      neonicotinoid imidacloprid, a moderate hazard was found when only invertebrate
      immobilization, and not lethality, data were considered. Environ Toxicol Chem
      2018;37:1430-1445. (c) 2018 SETAC.

PMID- 29336496
TI  - Donepezil Reverses Dendritic Spine Morphology Adaptations and Fmr1 Epigenetic
      Modifications in Hippocampus of Adult Rats After Adolescent Alcohol Exposure.
AB  - BACKGROUND: Adolescent intermittent ethanol (AIE) exposure produces persistent
      impairments in cholinergic and epigenetic signaling and alters markers of
      synapses in the hippocampal formation, effects that are thought to drive
      hippocampal dysfunction in adult rodents. Donepezil (Aricept), a cholinesterase
      inhibitor, is used clinically to ameliorate memory-related cognitive deficits.
      Given that donepezil also prevents morphological impairment in preclinical models
      of neuropsychiatric disorders, we investigated the ability of donepezil to
      reverse morphological and epigenetic adaptations in the hippocampus of adult rats
      exposed to AIE. Because of the known relationship between dendritic spine density
      and morphology with the fragile X mental retardation 1 (Fmr1) gene, we also
      assessed Fmr1 expression and its epigenetic regulation in hippocampus after AIE
      and donepezil pretreatment. METHODS: Adolescent rats were administered
      intermittent ethanol for 16 days starting on postnatal day 30. Rats were treated
      with donepezil (2.5 mg/kg) once a day for 4 days starting 20 days after the
      completion of AIE exposure. Brains were dissected out after the fourth donepezil
      dose, and spine analysis was completed in dentate gyrus granule neurons. A
      separate cohort of rats, treated identically, was used for molecular studies.
      RESULTS: AIE exposure significantly reduced dendritic spine density and altered
      morphological characteristics of subclasses of dendritic spines. AIE exposure
      also increased mRNA levels and H3-K27 acetylation occupancy of the Fmr1 gene in
      hippocampus. Treatment of AIE-exposed adult rats with donepezil reversed both the
      dendritic spine adaptations and epigenetic modifications and expression of Fmr1.
      CONCLUSIONS: These findings indicate that AIE produces long-lasting decreases in
      dendritic spine density and changes in Fmr1 gene expression in the hippocampal
      formation, suggesting morphological and epigenetic mechanisms underlying
      previously reported behavioral deficits after AIE. The reversal of these effects
      by subchronic, post-AIE donepezil treatment indicates that these AIE effects can
      be reversed by up-regulating cholinergic function.

PMID- 29336497
TI  - Effects of treatment with Maraviroc a CCR5 inhibitor on a human hepatic stellate
      cell line.
AB  - After an acute liver damage, tissue regeneration repairs lesions with degradation
      of deposed fibrotic material, while mechanisms of tissue restoration are
      persistently activated following several repeated injuries, inducing deposition
      of extracellular matrix. (ECM). Factors responsible for ECM remodeling have been
      identified in a pathway involving a family of zinc-dependent enzyme matrix
      metalloproteinases (MMPs), together with tissue inhibitor of metalloproteinases
      (TIMPs). Recent experimental models suggested a role of CCR5 receptor in the
      genesis of liver fibrosis. Drawing from these background we decided to evaluate
      the effects of the treatment with the CCR5 inhibitor Maraviroc on LX-2, a human
      hepatic stellate cell line (HSC). Treatment with Maraviroc resulted in a block in
      S phase of LX-2 cells with increased expression levels of cyclin D1 and p21 while
      the expression of p53 was reduced. Treatment with Maraviroc was also able to
      block the accumulation of fibrillar collagens and extracellular matrix proteins
      (ECM), as demonstrated by the decrease of specific markers as Collagen type I,
      alpha-SMA, and TGF-beta1. In addition we observed a down regulation of both
      metalloproteins (MMP-2, MMP-9), used for the degradation of the extracellular
      matrix and their inhibitors (TIMP-1, TIMP-2). The identification of a compound
      that may modulate the dynamic of liver fibrosis could be crucial in all chronic
      liver diseases. Maraviroc could play an important role because, in addition to
      its own anti-HIV activity, it could reduce the release of pro-inflammatory
      citokynes implicated in liver fibrogenesis.

PMID- 29336498
TI  - Erratum for Ann. N.Y. Acad. Sci. 2009. 1173: 670-674.

PMID- 29336499
TI  - Ecologically Driven Ultrastructural and Hydrodynamic Designs in Stomatopod
      Cuticles.
AB  - Ecological pressures and varied feeding behaviors in a multitude of organisms
      have necessitated the drive for adaptation. One such change is seen in the
      feeding appendages of stomatopods, a group of highly predatory marine
      crustaceans. Stomatopods include "spearers," who ambush and snare soft bodied
      prey, and "smashers," who bludgeon hard-shelled prey with a heavily mineralized
      club. The regional substructural complexity of the stomatopod dactyl club from
      the smashing predator Odontodactylus scyllarus represents a model system in the
      study of impact tolerant biominerals. The club consists of a highly mineralized
      impact region, a characteristic Bouligand architecture (common to arthropods),
      and a unique section of the club, the striated region, composed of highly aligned
      sheets of mineralized fibers. Detailed ultrastructural investigations of the
      striated region within O. scyllarus and a related species of spearing stomatopod,
      Lysiosquillina maculate show consistent organization of mineral and organic, but
      distinct differences in macro-scale architecture. Evidence is provided for the
      function and substructural exaptation of the striated region, which facilitated
      redeployment of a raptorial feeding appendage as a biological hammer. Moreover,
      given the need to accelerate underwater and "grab" or "smash" their prey, the
      spearer and smasher appendages are specifically designed with a significantly
      reduced drag force.

PMID- 29336500
TI  - 9,9'-Bifluorenylidene-Core Perylene Diimide Acceptors for As-Cast Non-Fullerene
      Organic Solar Cells: The Isomeric Effect on Optoelectronic Properties.
AB  - Two different non-fullerene small-molecule acceptors, m-PIB and p-PIB, based on
      9,9'-bifluorenylidene (BF) and perylene diimide (PDI) were designed and
      synthesized. Four beta-substituted PDIs were linked to BF in different positions.
      Based on DFT analysis, derivative p-PIB exhibited reduced intramolecular twisting
      between the PDI moieties, more delocalized wave function, and sufficiently wider
      pi-electron delocalization than that of m-PIB. The absorption ability of p-PIB
      was enhanced due to increased intermolecular interactions. By blending p-PIB with
      poly{4,8-bis[5-(2ethylhexyl)thiophen-2-yl]benzo[1,2-b:4,5-b']dithiophene-co-3
      fluorothieno[3,4-b]-thiophene-2-carboxylate} (PTB7-Th), organic solar cells
      (OSCs) based on p-PIB obtained a maximum power conversion efficiency of 5.95 %
      without any treatments. Due to the improved and balanced hole and electron
      mobilities, the short-circuit current and fill factor of OSCs based on PTB7-Th
      and p-PIB were significantly increased. The AFM and TEM results revealed that the
      PTB7-Th:p-PIB film had favorable nanoscale phase separation and formed a
      bicontinuous interpenetrating network.

PMID- 29336501
TI  - Uncontrolled asthmatics have increased FceRI+ and TGF-beta-positive MCTC mast
      cells and collagen VI in the alveolar parenchyma.
AB  - BACKGROUND: Asthma has been associated with increased collagen deposition in both
      conducting airways and alveolar parenchyma. Mast cells (MCs) are key effector
      cells in asthma and have the ability to affect collagen synthesis. However, the
      link between clinical control and changes in bronchial and alveolar MC phenotypes
      and specific collagens in controlled and uncontrolled asthma remains unknown.
      OBJECTIVE: To investigate MC phenotypes in correlation with deposition of
      specific collagen subtypes in patients with controlled and uncontrolled asthma as
      well as to healthy controls. METHODS: The tissue expression of IgE+ ,
      FcepsilonRI+ and TGF-beta+ MCs, as well as immunoreactivity of collagen I, III
      and VI, was assessed using immunohistochemistry on bronchial and transbronchial
      biopsies from controlled asthmatics (n = 9), uncontrolled asthmatics (n = 16) and
      healthy controls (n = 8). RESULTS: In the alveolar parenchyma, the total number
      of MCs, as well as the number of FcepsilonRI+ MCs and pro-fibrotic TGF-beta+
      MCTC, was significantly increased in uncontrolled asthma compared to both
      controlled asthma and healthy controls. The proportion of TGF-beta+ MCTC
      correlated positively to an increased immunoreactivity of alveolar collagen VI
      but not collagen I and III. Collagen VI was increased in the alveolar parenchyma
      of uncontrolled asthmatics compared to controlled asthmatics. Controlled
      asthmatics had an increased deposition of alveolar collagen I. In bronchi, the
      immunoreactivity of collagen I was increased in both controlled and uncontrolled
      asthmatics while collagen III was increased only in controlled asthmatics.
      CONCLUSIONS: Patients with uncontrolled atopic asthma have an altered pro
      fibrotic MCTC phenotype in the alveolar parenchyma that is associated with
      alveolar collagen VI. The present data thus support distal lung mast cell and
      matrix changes as histopathological features of asthma that may be of particular
      clinical relevance in patients who have remaining symptoms despite conventional
      inhaler therapy.

PMID- 29336502
TI  - Nursing teamwork in a health system: A multisite study.
AB  - AIM: The aim of this study was to examine how the facets of teamwork exist among
      nurse-only teams in acute and continuing care settings. BACKGROUND: The health
      care 'team' conventionally describes the interdisciplinary team in both
      literature and practice. Nursing-specific teams are rarely considered in the
      literature. An examination of this specific professional cohort is important to
      understand how teamwork exists among those who provide the majority of patient
      care. METHOD: This was a descriptive, comparative, cross-sectional study using
      the Nursing Teamwork Survey to measure teamwork of nursing-based teams among 1414
      participants in multiple acute care environments across a large Midwestern health
      system. RESULTS: The characteristics of nursing teams were analysed. The results
      from the subscales within the teamwork model showed that nursing teams had a good
      understanding of the various roles and responsibilities. However, nurse team
      members held a more individualistic rather than collective team-oriented mindset.
      CONCLUSIONS AND IMPLICATIONS FOR NURSING MANAGEMENT: Increased teamwork has a
      positive effect on job satisfaction, staffing efficiencies, retention and care
      delivery. Nurse leaders can use the information provided in this study to target
      the aspects of highly functioning teams by improving team orientation, trust and
      backup behaviours.

PMID- 29336503
TI  - Sappinia sp. (Amoebozoa: Thecamoebida) and Rosculus sp. (SAR: Cercozoa) Isolated
      From King Penguin Guano Collected in the Subantarctic (South Georgia, Salisbury
      Plain) and their Coexistence in Culture.
AB  - Two amoeboid organisms of the genera Sappinia Dangeard, 1896 and Rosculus Hawes,
      1963 were identified in a sample containing king penguin guano. This sample,
      collected in the Subantarctic, enlarges the list of fecal habitats known for the
      presence of coprophilic amoebae. The two organisms were co-isolated and
      subcultured for over 6 mo, with continuous efforts being invested to separate
      each one from the mixed culture. In the mixed culture, Rosculus cells were fast
      growing, tolerated changes in culturing conditions, formed cysts, and evidently
      were attracted by Sappinia trophozoites. The separation of the Rosculus strain
      was accomplished, whereas the Sappinia strain remained intermixed with
      inseparable Rosculus cells. Sappinia cell populations were sensitive to changes
      in culturing conditions; they improved with reduction of Rosculus cells in the
      mixed culture. Thick-walled cysts, reportedly formed by Sappinia species, were
      not seen. The ultrastructure of both organisms was congruent with the currently
      accepted generic characteristics; however, some details were remarkable at the
      species level. Combined with the results of phylogenetic analyses, our findings
      indicate that the ultrastructure of the glycocalyx and the presence/absence of
      the Golgi apparatus in differential diagnoses of Sappinia species require a
      critical re-evaluation.

PMID- 29336504
TI  - Wolbachia-induced transcription factor GATA4 suppresses ovary-specific genes
      blastoderm-specific protein 25D and imaginal disc growth factor.
AB  - The endosymbiotic bacterium Wolbachia infects a wide array of insect hosts and
      has been implicated in a range of biological modifications as a consequence of
      its infection. Previously, it was shown that the transcription factor GATA4 was
      significantly induced in Wolbachia wMelPop-CLA strain infected Aedes aegypti
      whole mosquitoes and cells. Here, we provide evidence that this induction also
      occurs in mosquito ovaries where the ovary-specific genes blastoderm-specific
      protein 25D (Bsg25D) and imaginal disc growth factor (Disc) are suppressed by
      Wolbachia. We further demonstrate that transcriptional depletion of GATA4 results
      in upregulation of both genes and conversely its overexpression leads to
      downregulation of the genes, suggesting that Wolbachia-induced GATA4 plays a
      suppressive regulatory role with regards to Bsg25D and Disc expression in
      mosquito ovaries. When the Disc gene was silenced in mosquitoes, we did not
      observe any difference in the number of mature ovarian follicles developed
      between treatment groups. However, we did find a significant delay in the
      hatching of eggs that had been laid by Disc knockdown mosquitoes.

PMID- 29336505
TI  - Signalling transduction events involved in agonist-induced PGE2/EP4 receptor
      externalization in cultured rat dorsal root ganglion neurons.
AB  - BACKGROUND: Prostaglandin E2 (PGE2) enriched in inflamed tissues contributes to
      chronic pain by sensitizing nociceptive dorsal root ganglion (DRG) neurons
      (nociceptors). Of four PGE2 receptors (EP1-4), EP4 plays a major role in PGE2
      induced nociceptor sensitization. We have previously reported that PGE2 or EP4
      agonists stimulated EP4 externalization in cultured DRG neurons and this event
      contributes to nociceptor sensitization. However, the signalling transduction
      events governing this event remain unknown. METHODS: In this study, using
      antibody-based externalization assay, we examined EP subtypes and multiple
      signalling transduction events involved in PGE2-induced EP4 externalization in
      cultured DRG neurons. RESULTS: In addition to EP4 agonist, EP2 agonist, to a
      lesser extent, also induced EP4 externalization while EP1 and EP3 agonists had no
      effect. The extracellular and intracellular calcium chelators, the inhibitors of
      CaMKII, cAMP, PKA, PKC, PKCepsilon, PLC, MAPKs, PI3K and Akt suppressed agonist
      induced EP4 externalization. The activator of AC, two PKA-specific cAMP analogues
      and one Epac-specific cAMP analogue also induced EP4 externalization. ELISA
      showed that double sequential exposures to EP4 agonists induced a greater release
      of pain peptide CGRP from cultured DRG neurons than a single exposure, an event
      blocked by the inhibitor of anterograde transport from ER/Golgi complex to cell
      surface. CONCLUSIONS: Taken together, these data suggest that mobilization of
      extracellular and intracellular calcium as well as the activation of CaMKII,
      cAMP/PKA, cAMP/Epac, PKC/PKCepsilon, MAPKs, PI3K-Akt and PLC signalling
      transduction pathways are involved in agonist-induced EP4 externalization.
      Agonist-enhanced EP4 externalization increases EP4 cell surface abundance and
      activity, thus enhancing nociceptor sensitization. SIGNIFICANCE: This study adds
      mechanistic information regarding signalling transduction events involved in
      agonist-induced EP4 cell surface trafficking. EP4 and EP2 (to lesser extent)
      receptors, extra- and intracellular Ca++ , CaKMII, cAMP, PKA, PKC, PKCepsilon,
      PLC, MAPK, PI3K and Akt are involved in this event. Agonist-induced EP4
      externalization contributes to enhanced nociceptor sensitization.

PMID- 29336506
TI  - Influence of culture change on the perception of fear and anxiety pathways in
      Endodontics: A pilot proof of concept study.
AB  - This study assessed the influence of cultural changes (known as acculturation) on
      pathways of fear and anxiety in Endodontics. A purposive sampling technique
      identified patients of Saudi Arabian descent living in Australia and Saudi
      Arabia. Only patients with root canal fillings (or treatment planned for
      endodontic treatment) were included. Patients with intellectual disabilities,
      surgical root therapy, and aged under 20 were excluded. Consenting patients
      attending the dental clinics of University of Griffith University, Australia and
      University of Dammam, Saudi Arabia completed the "My Endodontic Fear
      Questionnaire." Three hundred and twenty-four patients (21-75 years) were
      included, 90% of participants reported more than one pathway. Australian Saudi
      Arabians mainly utilised vicarious pathway (94.9%), whilst Saudi Arabians
      utilised the verbal threat (93.5%) and parental pathway (78.3%). This study
      highlights the possible role of acculturation on the perception of fear and
      anxiety in Endodontics; however, further research with other ethnic groups is
      essential to enhance our understanding.

PMID- 29336507
TI  - "LEARN"ing what is important to children and young people with intellectual
      disabilities when they are in hospital.
AB  - BACKGROUND: The need to review health service provision for children and young
      people (CYP) with disabilities and their families in the United Kingdom has been
      expressed in multiple reports: the most consistent message being that services
      need to be tailored to meet their individual needs. Our aim was to understand the
      hospital-related needs and experiences of CYP with intellectual disabilities.
      METHOD: An ethnographic study of a neurosciences ward and outpatient department
      was conducted within a paediatric tertiary hospital setting. RESULTS: Five
      themes, developed using the acronym LEARN, explained what is important to CYP
      with intellectual disabilities in hospital: (i) little things make the biggest
      difference, (ii) eliminate unnecessary waiting, (iii) avoid boredom, (iv) routine
      and home comforts are key and (v) never assume. CONCLUSIONS: It is imperative
      that the present authors continue to challenge the idea that it is acceptable to
      exclude CYP with intellectual disabilities from research because of their
      inability to participate.

PMID- 29336508
TI  - National audit of perinatal HIV infections in the UK, 2006-2013: what lessons can
      be learnt?
AB  - OBJECTIVES: The aim of the study was to investigate circumstances surrounding
      perinatal transmissions of HIV (PHIVs) in the UK. METHODS: The National Study of
      HIV in Pregnancy and Childhood conducts comprehensive surveillance of all
      pregnancies in women diagnosed with HIV infection and their infants in the UK;
      reports of all HIV-diagnosed children are also sought, regardless of country of
      birth. Children with PHIV born in 2006-2013 and reported by 2014 were included in
      an audit, with additional data collection via telephone interviews with
      clinicians involved in each case. Contributing factors for each transmission were
      identified, and cases described according to main likely contributing factor, by
      maternal diagnosis timing. RESULTS: A total of 108 PHIVs were identified. Of the
      41 (38%) infants whose mothers were diagnosed before delivery, it is probable
      that most were infected in utero, around 20% intrapartum and 20% through
      breastfeeding. Timing of transmission was unknown for most children of
      undiagnosed mothers. For infants born to diagnosed women, the most common
      contributing factors for transmission were difficulties with engagement and/or
      antiretroviral therapy (ART) adherence in pregnancy (14 of 41) and late antenatal
      booking (nine of 41); for the 67 children with undiagnosed mothers, these were
      decline of HIV testing (28 of 67) and seroconversion (23 of 67). Adverse social
      circumstances around the time of pregnancy were reported for 53% of women,
      including uncertain immigration status, housing problems and intimate partner
      violence. Eight children died, all born to undiagnosed mothers. CONCLUSIONS:
      Priority areas requiring improvement include reducing incident infections,
      improving ART adherence and facilitating better engagement in care, with
      attention to addressing the health inequalities and adverse social situations
      faced by these women.

PMID- 29336509
TI  - The investigation of substituent effects on the fragmentation pathways of
      pentacoordinated phenoxyspirophosphoranes by ESI-MSn.
AB  - The fragmentation pathways of pentacoordinated phenoxyspirophosphoranes were
      investigated in the positive mode by electrospray ionization multistage mass
      spectrometry. The results demonstrate that the sodium adducts of the title
      compounds undergo two competitive fragmentation pathways, and the fragmentation
      patterns are heavily dependent on the various substituent patterns at the
      phenolic group. An electron-withdrawing substituent at the ortho-position always
      results in the removal of a corresponding phenol analogue, while cleavage by
      spiroring opening becomes the predominant fragmentation pathway if an electron
      donating substituent is at the phenolic group. The substituent effects on the
      competitive fragmentation pathways were further elucidated by theoretical
      calculations, single crystal structure analysis, and high-resolution mass
      spectrometry. The results contribute to the understanding of the gas-phase
      fragmentation reactions and the structure identification of spirophosphorane
      analogues by electrospray ionization multistage mass spectrometry.

PMID- 29336510
TI  - Hierarchy of Asymmetry at Work: Chain-Dependent Helix-to-Helix Interactions in
      Supramolecular Polymers.
AB  - A detailed investigation of the hierarchy of asymmetry operating in the self
      assembly of achiral (1) and chiral ((S)-2 and (R)-3) 1,3,5
      triphenylbenzenetricarboxamides (TPBAs) is reported. The aggregation of these
      TPBAs is conditioned by the point chirality at the peripheral side chains for (S)
      2 and (R)-3. An efficient helix-to-helix interaction that goes further in the
      organization of fibrillar bundles is experimentally detected and theoretically
      supported only for the achiral TPBA 1. The effective interdigitation of the
      achiral aliphatic side chains produces a social self-sorting to form
      preferentially heterochiral macromolecular aggregates.

PMID- 29336511
TI  - Differential visual ornamentation between brood parasitic and parental cuckoos.
AB  - The evolution of brood parasitism should affect adult phenotypic traits due to
      sexual selection as well as the parasite-host interactions, although it is rarely
      focused on. Sexual selection theory predicts extravagant secondary sexual
      characteristics in brood parasites whereas immature-like modest sexual
      characteristics in parental species. This is because juvenile-like immature
      traits can attract mates by exploiting parental care for young (i.e. attraction
      to young), and because the good parent process, which favours traits that signal
      parental care ability, would constrain the evolution of costly secondary sexual
      characteristics due to evolutionary trade-offs between parental investment and
      sexually selected traits. Using a phylogenetic comparative approach, we studied
      plumage and bare-part characteristics of adults in relation to brood parasitism
      in cuckoos (family Cuculidae), in which brood parasitism together with loss of
      parental care has evolved three times. As predicted, we found that nonparasitic
      cuckoos had plumage more similar to the juveniles than did brood parasitic
      cuckoos. Furthermore, nonparasitic cuckoos had a higher probability of having
      additional bare skin, that is a seemingly less costly, hatchling-like trait, than
      did brood parasitic cuckoos. This finding further supports the link between
      parental care and sexual selection, although the influence of a parasite-host
      interaction cannot be excluded. The analysis of evolutionary pathways suggested
      interdependent evolution of additional bare skin and brood parasitism. Brood
      parasitism together with the loss of parental care may prevent the maintenance of
      a modest phenotype similar to the young, and vice versa in some cases.

PMID- 29336512
TI  - Using field data to quantify chemical impacts on wildlife population viability.
AB  - Environmental pollution is an important driver of biodiversity loss. Yet, to
      date, the effects of chemical exposure on wildlife populations have been
      quantified for only a few species, mainly due to a lack of appropriate laboratory
      data to quantify chemical impacts on vital rates. In this study, we developed a
      method to quantify the effects of toxicant exposure on wildlife population
      persistence based on field monitoring data. We established field-based vital-rate
      response functions for toxicants, using quantile regression to correct for the
      influences of confounding factors on the vital rates observed, and combined the
      response curves with population viability modelling. We then applied the method
      to quantify the impact of DDE on three bird species: the White-tailed Eagle, Bald
      Eagle, and Osprey. Population viability was expressed via five population
      extinction vulnerability metrics: population growth rate (r1 ), critical patch
      size (CPS), minimum viable population size (MVP), probability of population
      extirpation (PE), and median time to population extirpation (MTE). We found that
      past DDE exposure concentrations increased population extirpation vulnerabilities
      of all three bird species. For example, at DDE concentrations of 25 mg/kg wet
      mass of egg (the maximum historic exposure concentration reported in literature
      for the Osprey), r1 became small (White-tailed Eagle and Osprey) or close to zero
      (Bald Eagle), the CPS increased up to almost the size of Connecticut (White
      tailed Eagle and Osprey) or West Virginia (Bald Eagle), the MVP increased up to
      approximately 90 (White-tailed Eagle and Osprey) or 180 breeding pairs (Bald
      Eagle), the PE increased up to almost certain extirpation (Bald Eagle) or only
      slightly elevated levels (White-tailed Eagle and Osprey) and the MTE became
      within decades (Bald Eagle) or remained longer than a millennium (White-tailed
      Eagle and Osprey). Our study provides a method to derive species-specific field
      based response curves of toxicant exposure, which can be used to assess
      population extinction vulnerabilities and obtain critical levels of toxicant
      exposure based on maximum permissible effect levels. This may help conservation
      managers to better design appropriate habitat restoration and population recovery
      measures, such as reducing toxicant levels, increasing the area of suitable
      habitat or reintroducing individuals.

PMID- 29336513
TI  - Palladium-Catalyzed Asymmetric Aminohydroxylation of 1,3-Dienes.
AB  - A PdII -catalyzed asymmetric aminohydroxylation of 1,3-dienes with N-tosyl-2
      aminophenols was developed by making use of a chiral pyridinebis(oxazoline)
      ligand. The highly regioselective reaction provides direct and efficient access
      to chiral 3,4-dihydro-2H-1,4-benzoxazines in high yield and enantioselectivity
      (up to 96:4 e.r.). The reaction employs readily available N-tosyl-2-aminophenols
      as a unique aminohydroxylation reagent and is complementary to known asymmetric
      aminohydroxylation methods.

PMID- 29336514
TI  - Machine-learned analysis of quantitative sensory testing responses to noxious
      cold stimulation in healthy subjects.
AB  - BACKGROUND: Pain in response to noxious cold has a complex molecular background
      probably involving several types of sensors. A recent observation has been the
      multimodal distribution of human cold pain thresholds. This study aimed at
      analysing reproducibility and stability of this observation and further
      exploration of data patterns supporting a complex background. METHOD: Pain
      thresholds to noxious cold stimuli (range 32-0  degrees C, tonic: temperature
      decrease -1  degrees C/s, phasic: temperature decrease -8  degrees C/s) were
      acquired in 148 healthy volunteers. The probability density distribution was
      analysed using machine-learning derived methods implemented as Gaussian mixture
      modeling (GMM), emergent self-organizing maps and self-organizing swarms of data
      agents. RESULTS: The probability density function of pain responses was trimodal
      (mean thresholds at 25.9, 18.4 and 8.0  degrees C for tonic and 24.5, 18.1 and
      7.5  degrees C for phasic stimuli). Subjects' association with Gaussian modes was
      consistent between both types of stimuli (weighted Cohen's kappa = 0.91).
      Patterns emerging in self-organizing neuronal maps and swarms could be associated
      with different trends towards decreasing cold pain sensitivity in different
      Gaussian modes. On self-organizing maps, the third Gaussian mode emerged as
      particularly distinct. CONCLUSION: Thresholds at, roughly, 25 and 18  degrees C
      agree with known working temperatures of TRPM8 and TRPA1 ion channels,
      respectively, and hint at relative local dominance of either channel in
      respective subjects. Data patterns suggest involvement of further distinct
      mechanisms in cold pain perception at lower temperatures. Findings support data
      science approaches to identify biologically plausible hints at complex molecular
      mechanisms underlying human pain phenotypes. SIGNIFICANCE: Sensitivity to pain is
      heterogeneous. Data-driven computational research approaches allow the
      identification of subgroups of subjects with a distinct pattern of sensitivity to
      cold stimuli. The subgroups are reproducible with different types of noxious cold
      stimuli. Subgroups show pattern that hints at distinct and inter-individually
      different types of the underlying molecular background.

PMID- 29336515
TI  - Expectations and experiences of patients with osteoarthritis undergoing total
      joint arthroplasty: An integrative review.
AB  - BACKGROUND: The effectiveness of educational interventions for osteoarthritic
      patients undergoing total joint arthroplasty remains inconclusive. It is
      essential to understand the educational needs of these patients from their
      perspectives. AIM: The aim of this study was to systematically summarize and
      synthesize osteoarthritic patients' expectations and experiences in undergoing
      total joint arthroplasty to identify their educational needs. DESIGN: An
      integrative review was conducted. METHODS: Twenty studies (13 qualitative and 7
      quantitative), published between 2006 and 2016, were independently appraised by 2
      reviewers using the Critical Appraisal Skills Programme checklist for qualitative
      studies and the Joanna Briggs Institute Critical Appraisal Tools for quantitative
      studies. Data were analysed using thematic analysis, and the findings were
      synthesized in a narrative summary. RESULTS: Six themes describing patients'
      preoperative and post-operative educational needs were identified: (1)
      preoperative anxiety, (2) unrealistic expectations of recovery, (3) post
      operative pain, (4) regaining functional abilities, (5) physical and
      psychological sense of loss, and (6) lack of continuity of care. CONCLUSION: This
      review is the first to capture the osteoarthritic patients' educational needs
      from their perspectives. The biopsychosocial model can address the
      multidimensionality (biological, psychological, and social) of patients'
      educational needs. A robust infrastructure supporting interprofessional
      collaborative practice and continuity of care should be adopted to enhance
      current educational efforts.

PMID- 29336516
TI  - Neglect of attention to reproductive health in women with HIV infection:
      contraceptive use and unintended pregnancies in the Swiss HIV Cohort Study.
AB  - OBJECTIVES: Women with HIV infection are mainly of reproductive age and need
      safe, effective and affordable contraception to avoid unintended pregnancies. The
      aim of this study was to evaluate contraceptive use and unintended pregnancies in
      this population in Switzerland. METHODS: A self-report anonymous questionnaire on
      contraceptive methods, adherence to them, and unintended pregnancies was
      completed by women included in the Swiss HIV Cohort Study (SHCS) between November
      2013 and June 2014. Sociodemographic characteristics and information related to
      combined antiretroviral therapy and HIV disease status were obtained from the
      SHCS database. RESULTS: Of 462 women included, 164 (35.5%) reported not using any
      contraception. Among these, 65 (39.6%) reported being sexually active, although
      29 (44.6%) were not planning a pregnancy. Of 298 women using contraception, the
      following methods were reported: condoms, 219 (73.5%); oral hormonal
      contraception, 32 (10.7%); and intrauterine devices, 28 (9.4%). Among all women
      on contraception, 32 (10.7%) reported using more than one contraceptive method
      and 48 (16%) had an unintended pregnancy while on contraception (18, condoms; 16,
      oral contraception; four, other methods). Of these, 68.1% terminated the
      pregnancy and almost half (43.7%) continued using the same contraceptive method
      after the event. CONCLUSIONS: Family planning needs in HIV-positive women are not
      fully addressed because male condoms remained the predominant reported
      contraceptive method, with a high rate of unintended pregnancies. It is of utmost
      importance to provide effective contraception such as long-acting reversible
      contraceptives for women living with HIV.

PMID- 29336518
TI  - Seeded Polymerization through the Interplay of Folding and Aggregation of an
      Amino-Acid-based Diamide.
AB  - Amino acid based diamides are widely used as a substructure in supramolecular
      polymers and are also key components of polypeptides that help to understand
      protein folding. The interplay of folding and aggregation of a diamide was used
      to achieve seed-initiated supramolecular polymerization. For that purpose, a
      pyrene-substituted diamide was synthesized in which pyrene is used as a tracer to
      monitor the supramolecular polymerization. Thermodynamics and time-dependent
      studies revealed that the folding of the diamide moiety, via the formation of
      intramolecular hydrogen bonds, effectively prevents a spontaneous nucleation that
      leads to supramolecular polymerization. Under such out-of-equilibrium conditions,
      the addition of seeds successfully initiates the supramolecular polymerization.
      These results demonstrate the utility of such amino acid based diamides in
      programmable supramolecular polymerizations.

PMID- 29336517
TI  - Environmental Sequencing Fills the Gap Between Parasitic Haplosporidians and Free
      living Giant Amoebae.
AB  - Class Ascetosporea (Rhizaria; Endomyxa) comprises many parasites of
      invertebrates. Within this group, recent group-specific environmental DNA (eDNA)
      studies have contributed to the establishment of the new order Mikrocytida, a new
      phylogeny and characterization of Paramyxida, and illuminated the diversity and
      distribution of haplosporidians. Here, we use general and lineage-specific PCR
      primers to investigate the phylogenetic "gap" between haplosporidians and their
      closest known free-living relatives, the testate amoeba Gromia and reticulate
      amoeba Filoreta. Within this gap are Paradinium spp. parasites of copepods, which
      we show to be highly diverse and widely distributed in planktonic and benthic
      samples. We reveal a robustly supported radiation of parasites, ENDO-3, comprised
      of Paradinium and three further clades (ENDO-3a, ENDO-3b and SPP). A further
      environmental group, ENDO-2, perhaps comprising several clades, branches between
      this radiation and the free-living amoebae. Early diverging haplosporidians were
      also amplified, often associated with bivalves or deep-sea samples. The general
      primer approach amplified an overlapping set of novel lineages within ENDO-3 and
      Haplosporida, whereas the group-specific primer strategy, targeted to amplify
      from the earliest known divergent haplosporidians to Gromia, generated greater
      sequence diversity across part of this phylogenetic range.

PMID- 29336519
TI  - Management of venous thromboembolism: Time to measure our performance.

PMID- 29336520
TI  - Near-Infrared Triggered Decomposition of Nanocapsules with High Tumor
      Accumulation and Stimuli Responsive Fast Elimination.
AB  - A near-infrared (NIR) induced decomposable polymer nanocapsule is demonstrated.
      The nanocapsules are fabricated based on layer-by-layer co-assembly of azobenzene
      functionalized polymers and up/downconversion nanoparticles (U/DCNPs). When the
      nanocapsules are exposed to 980 nm light, ultraviolet/visible photons emitted by
      the U/DCNPs can trigger the photoisomerization of azobenzene groups in the
      framework. The nanocapsules could decompose from large-sized nanocapsule to small
      U/DCNPs. Owing to their optimized original size (ca. 180 nm), the nanocapsules
      can effectively avoid biological barriers, provide a long blood circulation (ca.
      5 h, half-life time) and achieve four-fold tumor accumulation. It can fast
      eliminate from tumor within one hour and release the loaded drugs for
      chemotherapy after NIR-induced dissociation from initial 180 nm capsules to small
      20 nm U/DCNPs.

PMID- 29336521
TI  - Identification and quantification of VOCs by proton transfer reaction time of
      flight mass spectrometry: An experimental workflow for the optimization of
      specificity, sensitivity, and accuracy.
AB  - Proton transfer reaction time of flight mass spectrometry (PTR-ToF-MS) is a
      direct injection MS technique, allowing for the sensitive and real-time
      detection, identification, and quantification of volatile organic compounds. When
      aiming to employ PTR-ToF-MS for targeted volatile organic compound analysis, some
      methodological questions must be addressed, such as the need to correctly
      identify product ions, or evaluating the quantitation accuracy. This work
      proposes a workflow for PTR-ToF-MS method development, addressing the main issues
      affecting the reliable identification and quantification of target compounds. We
      determined the fragmentation patterns of 13 selected compounds (aldehydes, fatty
      acids, phenols). Experiments were conducted under breath-relevant conditions
      (100% humid air), and within an extended range of reduced electric field values
      (E/N = 48-144 Td), obtained by changing drift tube voltage. Reactivity was
      inspected using H3 O+ , NO+ , and O2+ as primary ions. The results show that a
      relatively low (<90 Td) E/N often permits to reduce fragmentation enhancing
      sensitivity and identification capabilities, particularly in the case of
      aldehydes using NO+ , where a 4-fold increase in sensitivity is obtained by means
      of drift voltage reduction. We developed a novel calibration methodology, relying
      on diffusion tubes used as gravimetric standards. For each of the tested
      compounds, it was possible to define suitable conditions whereby experimental
      error, defined as difference between gravimetric measurements and calculated
      concentrations, was 8% or lower.

PMID- 29336522
TI  - Continued root maturation despite persistent apical periodontitis of immature
      permanent teeth after failed regenerative endodontic therapy.
AB  - Three immature permanent teeth with pulp necrosis and apical periodontitis were
      treated with regenerative endodontic therapy (RET), which included root canal
      disinfection with sodium hypochlorite irrigation, intra-canal medication with
      calcium hydroxide paste, 17% EDTA rinse, induction of periapical bleeding into
      the canal, collagen matrix and MTA coronal seal, and composite resin restoration
      of access cavities. After different periods of follow-up, it was observed that
      continued root maturation, especially apical closure occurred despite persistent
      apical periodontitis of immature permanent teeth after failed RET. This finding
      is of interest as the secondary goal of further root maturation occurred despite
      failure of the primary goal of elimination of clinical symptom/sign and
      periapical inflammation. The possible biological mechanisms that could allow for
      further root maturation to occur in spite of persistent root canal infection of
      immature permanent teeth are discussed. Based on these observations, the biology
      of wound healing of immature permanent teeth after injury is not fully understood
      and should be further investigated. This case report demonstrates that whilst
      further root maturation is considered a successful outcome for teeth treated with
      RET, the primary objective must be the resolution of the signs and symptoms of
      apical periodontitis.

PMID- 29336523
TI  - Quadratus lumborum block in management of severe pain after uterine artery
      embolization.
AB  - BACKGROUND AND OBJECTIVES: The quadratus lumborum (QL) block has been widely used
      for acute postoperative pain management after numerous surgical procedures
      including urological, abdominal, gynaecological and orthopaedic surgical
      procedures. The local anaesthetic spread in this area can provide unilateral
      sensory block in T6-L2 dermatomes. We performed bilateral quadratus lumborum
      block for the management of acute pain after the uterine artery embolization
      (UAE). METHODS: A 43-year-old woman was admitted to the gynaecology department of
      Mother and Child Hospital, University Medical Center, for uterine artery
      embolization. Shortly, after successful completion of the UAE procedure, the
      patient began to complain of severe pain in the lower abdomen rated as a 9 on a
      verbal analogue scale (VAS) of 0-10. Intravenous tramadol 100 mg was infused over
      30 min with minimal reduction in pain. Trimeperidine 20 mg was then infused over
      30 min. Pain scores, however, remained 7-8/10 on the VAS. It was therefore
      decided to place a bilateral single-shot ultrasound-guided quadratus lumborum
      block. RESULTS: The procedure was well tolerated and brought notable pain relief.
      VAS declined from 8/10 to 5/10 after 30 min and to 3/10 at 60 min. Over the
      ensuing 24 h, VAS pain intensity remained 2-3/10. No further analgesics were
      necessary. CONCLUSION: A randomized control clinical trial is warranted to assess
      the efficacy of QL blockade and to compare it with other analgesic options in
      uterine artery embolization. Bilateral quadratus lumborum blockade may be an
      excellent pain control option after uterine artery embolization. SIGNIFICANCE:
      Uterine artery embolization is associated with significant postprocedural pain
      which can prove difficult to manage with opioids. Bilateral quadratus lumborum
      block may be an excellent pain control option - one that might significantly
      reduce not only pain, but also the need for opioids and perhaps even the need for
      hospitalization.

PMID- 29336524
TI  - Human Intestinal Dendritic Cells in Inflammatory Bowel Diseases.
AB  - Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative
      colitis, is a serious, costly, and persistent health problem with an estimated
      prevalence in Western countries around 0.5% of the general population; its
      socioeconomic impact is comparable with that for chronic diseases such as
      diabetes. Conventional treatment involves escalating drug regimens with
      concomitant side effects followed, in some cases, by surgical interventions,
      which are often multiple, mainly in Crohn's disease. The goal of finding a
      targeted gut-specific immunotherapy for IBD patients is therefore an important
      unmet need. However, to achieve this goal we first must understand how dendritic
      cells (DC), the most potent antigen present cells of the immune system, control
      the immune tolerance in the gastrointestinal tract and how their properties are
      altered in those patients suffering from IBD. In this review, we summarize the
      current available information regarding human intestinal DC subsets composition,
      phenotype, and function in the human gastrointestinal tract describing how, in
      the IBD mucosa, DC display pro-inflammatory properties, which drive disease
      progression. A better understanding of the mechanisms inducing DC abnormal
      profile in IBD may provide us with novel tools to perform tissue specific
      immunomodulation.

PMID- 29336525
TI  - Complications of curative radiation treatment for early prostate cancer.
AB  - AIM: To report the incidence of urological complications following curative
      radiation treatment for early prostate cancer, including minimally invasive
      urological procedures (MUIP), hospital admissions and open surgical procedures.
      Second malignancies following radiation are also reported and compared with
      patients undergoing a prostatectomy. METHODS: Included were patients receiving
      curative intent external beam radiation treatment for early prostate cancer
      between January 1, 2002, and December 31, 2009. Medical records were reviewed for
      baseline characteristics, treatment details and outcomes. Kaplan-Meier methods
      were used to derive the 5-year cumulative incidence of the urological outcomes
      and second malignancy. RESULTS: There were 439 patients identified. The median
      follow-up was 6.96 years. The median age was 69. A total of 56 patients developed
      a radiation related urological complication, 25 requiring hospital admission. The
      5-year cumulative incidence for an MIUP and admission was 3.95% (95% confidence
      interval (CI), 2.47-6.28) and 2.24% (95% CI, 1.17-4.27), respectively. There were
      no open surgical procedures. Further malignancy developed in 27 patients during
      the 5- to 9-year posttreatment period with a cumulative incidence of 10.7% (95%
      CI, 7.31-15.51). Of the comparator prostatectomy group, of the 265 eligible
      patients analyzed, 19 patients developed a second malignancy with a cumulative
      incidence of 9.92% (95% CI, 6.28-15.48). On log-rank testing, there was no
      difference in the cumulative incidence rates of second malignancy between 5 and 9
      years, following respective treatments (P  =  0.8554). CONCLUSIONS: The incidence
      of MUIP, hospital admissions and open surgical procedures following radiation is
      reassuringly low. The second malignancy rates are also low and similar to the
      rates in patients treated with a prostatectomy.

PMID- 29336526
TI  - Human Milk Oligosaccharides as Promising Antivirals.
AB  - Human milk oligosaccharides (HMOs) are diverse unconjugated carbohydrates that
      are highly abundant in human breast milk. These glycans are investigated in the
      context of exhibiting multiple functions in infant growth and development. They
      seem to provide protection against infectious diseases, including a number of
      poorly manageable viral infections. Although the potential mechanism of the HMO
      antiviral protection is rather broad, much of the current experimental work has
      focused on studying of HMO antiadhesive properties. HMOs may mimic structures of
      viral receptors and block adherence to target cells, thus preventing infection.
      Still, the potential of HMOs as a source for new antiviral drugs is relatively
      unexploited. This can be partly attributed to the extreme complexity of the virus
      carbohydrate interactions and technical difficulties in HMO isolation,
      characterization, and manufacturing procedures. Fortunately, we are currently
      entering a period of major technological advances that have enabled deeper
      insights into carbohydrate mediated viral entry, rational selection of HMOs as
      anti-entry inhibitors, and even evaluation of individual synthetic HMO
      structures. Here, we provide an up-to-date review on glycan binding studies for
      rotaviruses, noroviruses, influenza viruses, and human immunodeficiency viruses.
      We also discuss the preventive and therapeutic potential of HMOs as anti-entry
      inhibitors and address challenges on the route from fundamental studies to
      clinical trials.

PMID- 29336527
TI  - Sustainable Synthesis of Oxalic and Succinic Acid through Aerobic Oxidation of C6
      Polyols Under Mild Conditions.
AB  - The sustainable chemical industry encompasses a shift from the use of fossil
      carbon to renewable carbon. The synthesis of chemicals from nonedible biomass
      (cellulosic or oil) represents one of the key steps for "greening" the chemical
      industry. In this paper, we report the aerobic oxidative cleavage of C6 polyols
      (5-HMF, glucose, fructose and sucrose) to oxalic acid (OA) and succinic acid (SA)
      in water under mild conditions using M@CNT and M@NCNT (M=Fe, V; CNT=carbon
      nanotubes; NCNT=N-doped CNT), which, under suitable conditions, were recoverable
      and reusable without any loss of efficiency. The influence of the temperature, O2
      pressure (PO2 ), reaction time and stirring rate are discussed and the best
      reaction conditions are determined for an almost complete conversion of the
      starting material and a good OA yield of 48 %. SA and formic acid were the only
      co-products. The former could be further converted into OA by oxidation in the
      presence of formic acid, resulting in an overall OA yield of >62 %. This process
      was clean and did not produce organic waste nor gas emissions.

PMID- 29336528
TI  - Synthesis of Functionalized (eta5 -Indenyl)rhodium(III) Complexes and Their
      Application to C-H Bond Functionalization.
AB  - It has been established that reductive complexation of functionalized
      benzofulvenes, which are readily prepared from commercially available indene and
      2-methylindene, with RhCl3 in ethanol affords the corresponding indenyl
      rhodium(III) dichlorides bearing substituents at the 1- (H or CO2 Et), 2- (H or
      Me), and 3- [CH2 Ph or CH2 (2-MeOC6 H4 )] positions. The indenyl-rhodium(III)
      complexes bearing one ethoxycarbonyl group showed higher thermal stability and
      regioselectivity than our previously reported CpE RhIII complex toward the
      oxidative [3+2] annulation of acetanilides with internal alkynes.

PMID- 29336529
TI  - High prevalence of reduced thrombin generation and/or decreased platelet response
      in women with unexplained heavy menstrual bleeding.
AB  - INTRODUCTION: Heavy menstrual bleeding (HMB) is a condition that affects 20%-30%
      of women of reproductive age. HMB has a multifactorial pathophysiology, which is
      incompletely understood. HMB symptoms are very common in patients with
      established haemostasis defects, likewise, women with heavy menstrual bleeding
      have a higher prevalence of impaired Von Willebrand factor (VWF) levels and
      function, thrombocytopenia, impaired platelet function and impaired coagulation.
      The aim of this study was to quantify the prevalence of impaired platelet
      function, impaired coagulation and reduced VWF activity in patients with HMB.
      METHODS: We have used thrombin generation (TG), a flow cytometry-based platelet
      function test and a flow cytometry-based VWF function test to study haemostasis
      in 58 women (median age: 48.4 years, range 40-60 years) with HMB. In addition, we
      determined VWF antigen levels and VWF ristocetin co-factor activity in platelet
      poor plasma. Reference ranges of platelet function were measured in whole blood
      of 123 healthy volunteers, while reference ranges of TG were determined in
      platelet-poor plasma (PPP) of 126 healthy volunteers. RESULTS: Fourteen (24%)
      patients with HMB had impaired platelet function and 17 (29.3%) patients had
      impaired coagulation. Five patients (8.6%) had both impaired platelet function
      and impaired coagulation. Only 2 (3.4%) patients had an impaired VWF function or
      levels; one of them was in combination with impaired coagulation. CONCLUSION: Our
      approach in women with HMB using a high precision platelet function test in
      combination with thrombin generation showed impaired coagulation or impaired
      platelet function in more than 40% of the patients.

PMID- 29336530
TI  - Cut-point for Ki-67 proliferation index as a prognostic marker for glioblastoma.
AB  - INTRODUCTION: Ki-67 proliferation index (Ki-67 index) is used to quantify cell
      proliferation during histopathological assessment of various tumors including
      glioblastoma (GB). AIM: We aimed to assess correlation between Ki-67 index and
      overall survival in patients with GB and determine a cut-point for Ki-67 index
      that predicts for poorer survival. METHOD: Records of adult patients diagnosed
      with GB on histopathological specimens at a tertiary cancer center in Sydney
      between 1 January 2002 and 30 July 2012 were retrieved. Specimens of these
      patients were examined for quantification of Ki-67 staining by two independent
      pathologists. Patient, disease, treatment, and survival data were collected from
      hospital and cancer care service records. Statistical analysis was performed
      using proportional hazards models, Kaplan-Meier curves, and the minimum P-value
      approach. RESULT: Of the eligible 71 patients, 58% were males with median age of
      58 (range 18-87). Seventy-three percent of patients were of ECOG performance
      status 0-1. There was a statistically significant correlation between Ki-67 index
      and overall survival. In patients with Ki-67 > 22% (n = 36), 5-year survival was
      approximately 30% compared to 5% in those with Ki-67 <= 22% (n = 35; log-rank P
      value = 0.04; hazard ratio (HR) = 0.53; 95% confidence intervals (CI), 0.29
      0.97). CONCLUSION: This study demonstrates a positive correlation between Ki-67
      index and overall survival in patients with GB. Percentage staining of Ki-67 <
      22% appears to predict for poorer survival in GB.

PMID- 29336531
TI  - Nanobiotechnology of Carbon Dots: A Review.
AB  - In recent years, carbon dots (CDs) have gained increasing attention owing to
      their unique properties and enormous potential for several biomedical and
      technological applications. CDs are biocompatible, have a small size with a
      relatively large surface area, are photostable, and have customizable
      photoluminescence properties. This review is divided into the following
      discussions of CDs: general definitions; an overview of recent reviews; methods
      of green and classical synthesis; applications in bioimaging, involving
      supercapacitors, nanocarriers and nanomedicine; toxicological evaluations
      (including cytotoxic, genotoxic and anti-cancer properties of CDs); their
      conjugation with enzymes, biosensors, and cell labeling. Finally the remaining
      drawbacks and challenges of CD applications are highlighted. In this context,
      this article aims to provide critical insight and inspire further developments in
      the synthesis and application of CDs.

PMID- 29336532
TI  - Nanoscale Photodynamic Agents for Colorectal Cancer Treatment: A Review.
AB  - Colorectal cancer is the most common form of gastroenteric cancer worldwide.
      Photodynamic therapy is emerging as an attractive method to treat cancers.
      Candidate targets of photodynamic therapy include epidermal growth factor
      receptors, cholesterol and low-density lipoprotein, estrogen receptors, the
      nucleus and DNA, folic acid receptors, cholecystokinin A receptors, lectin
      saccharide receptors, and tumor-specific antibodies. Specifically, in colorectal
      tumors, anti-DR5 antibody and cancer-specific antibody moieties are involved.
      Cancer cells incorporate greater quantities of sugars, and glycoconjugated
      photosensitizer has remarkable internalization and cytotoxicity in
      colon/colorectal cancer cells. Simultaneously, to circumvent the bio-distribution
      limitation, other molecules, including lectins, Hyaluronic acid, and peptides,
      have also been considered for colorectal cancer. Other novel strategies
      indirectly targeting colorectal cancer include pH-responsive PS, enzymatically
      activated photosensitization, and cancer-suppressing immune cells, mainly
      macrophages. Recently, nanoparticles have gained attention as a versatile
      platform for multi-functional photodynamic therapy. In this review, we summarize
      the targeting strategies investigated and highlight the potential of
      nanoparticles for target photodynamic therapy in colorectal cancer.

PMID- 29336533
TI  - Targeted Nanocurcumin Therapy Using Annexin A2 Anitbody Improves Tumor
      Accumulation and Therapeutic Efficacy Against Highly Metastatic Breast Cancer.
AB  - A major challenge in pharmaceutical research is effective targeting strategies to
      their sites of action. Emerging knowledge and the current progress in
      nanotechnology based delivery systems has opened up exciting ways towards
      successful targeted nanodelivery systems. For cancer therapy, nanoparticle-based
      drug formulations hold several advantages over free drugs, including improved
      pharmacokinetics, enhanced tumor accumulation, reduced systemic exposure and side
      effects and better patient compliance. The goal of this study was to validate the
      in vivo targeting potential and evaluate the combinatorial therapeutic potential
      of novel Annexin A2 (AnxA2) antibody-conjugated curcumin loaded poly(lactic-co
      glycolic acid) (PLGA) nanoparticles (AnxA2-CPNP) against metastatic breast
      cancer. As a first step, we demonstrated that the cell-surface expression of
      AnxA2 is increases during breast cancer progression with very high expression in
      highly malignant cancer cells and basal expression in non-malignant cells. This
      confirmed AnxA2 as an excellent target for targeting our curcumin nanoparticles.
      Our results indicate that AnxA2-CPNP showed increased uptake in highly metastatic
      breast cancer cells than untargeted nanoparticles due to the differential AnxA2
      expression. Cell viability, plasmin generation and wound healing assays reveal
      that AnxA2-CPNPs effectively inhibited cell proliferation, invasion and
      migration, key elements for cancer growth and metastasis. Further, angiogenesis
      assay illustrated that AnxA2-CPNPs decreased the formation of tube capillaries,
      thus inhibiting neoangiogenesis, a critical element in tumor growth. Live animal
      imaging demonstrated that AnxA2-PNPs and AnxA2-CPNPs effectively targeted and
      accumulated in the tumor as seen by the increased fluorescence intensity on the
      live scans. Xenograft studies in mice showed significant regression of breast
      tumor as a result of both effective targeting, accumulation and sustained release
      of curcumin in the tumor. In conclusion, AnxA2-CPNPs were successfully validated
      for their breast tumor targeting potential and its improved therapeutic efficacy
      against metastatic breast cancer.

PMID- 29336534
TI  - Folic Acid Functionalized gamma-Cyclodextrin C60, A Novel Vehicle for Tumor
      Targeted Drug Delivery.
AB  - Folic acid (FA)-gamma cyclodextrin (gamma CD)-C60 was synthesized in this study
      as a carrier for tumor-targeted drug delivery to enhance the anticancer effect of
      carboplatin (CBP). FA-gamma CD and C60-CBP were prepared and C60-CBP was then
      entrapped into FA-gamma CD through host-guest effect. FA-gamma CD-C60
      significantly increased the intracellular uptake and release of CBP, thereby
      providing higher cytotoxicity against the HeLa cells with high expression of
      folate receptor (FR). In vivo experiments revealed that FA-gamma CD-C60-CBP had
      more significant anticancer effects than CBP alone, showing no obvious toxic
      effects on zebrafish at concentration as high as 500 MUg/mL. These results
      suggest that FA-gamma CD-C60 may provide an effective strategy for administration
      of antineoplastics, with great promise in future targeted therapy for cancers.

PMID- 29336536
TI  - Imprecise Percentages.

PMID- 29336535
TI  - Construction of Functional Targeting Daunorubicin Liposomes Used for Eliminating
      Brain Glioma and Glioma Stem Cells.
AB  - The highly infiltrative nature of brain glioma makes total surgical removal of
      cancerous cells virtually impossible. Regular chemotherapy plays an important
      role in eradicating the residual cancer cells but is ineffective in treating
      brain glioma due to the hindrance of drug penetration into the tumor site by the
      blood brain barrier (BBB) and the regeneration of cancer cells by glioma stem
      cells (GSCs). In this study, functional targeting daunorubicin liposomes were
      developed by modifying the liposomes with distearoylphosphatidylethanolamine
      polyethylene glycol-polyethylenimine (DSPE-PEG2000PEI600 and a lipid-glucose
      derivative (DSPE-PEG2000-GLU). The studies were performed in brain glioma and
      glioma stem cells in vitro and in brain glioma-bearing mice inoculated with the
      glioma stem cells. The results showed that the functional targeting daunorubicin
      liposomes were able to significantly transfer across the BBB and exhibited an
      obvious efficacy in killing glioma and glioma stem cells in mice. The action
      mechanisms of the functional targeting daunorubicin liposomes were related to
      their properties: long-duration circulation in the blood system, transport
      capability across the BBB, concentrated accumulation in the brain glioma site,
      and increased internalization by malignant cells and their mitochondria. This
      functional drug formulation showed anticancer efficacy through a direct cytotoxic
      effect and an apoptosis-inducing effect through the apoptotic signaling pathways
      in the cytoplasm and mitochondria of the cells. As a chemotherapy strategy for
      treating brain glioma, functional targeting daunorubicin liposomes have the
      potential to eliminate brain glioma along with glioma stem cells.

PMID- 29336538
TI  - Error in Abstract.

PMID- 29336537
TI  - Polymer-Encapsulated Abeta Peptide Fragments as an Oligomeric-Specific Vaccine
      for Alzheimer's Disease.
AB  - Vaccination is regarded as one of the most cost-effective and reliable methods
      for combating disease. We have developed a new method for an oligomeric Abeta
      specific AD vaccination using polymer micelle-encapsulated peptide fragments,
      which overcome many problems of vaccination associated with the direct use of the
      Abeta1-42 peptide. We studied different encapsulated forms of shortened Abeta
      peptides with and without the entire T cell epitope in an APP/PS1 mouse model.
      After two inoculations with encapsulated Abeta fragments, antibodies were
      produced in all mice with antibody titer greater than 1:12,800. No anti-polymer
      antibodies were detected after five inoculations, and none of the injected mice
      showed any adverse effects throughout experimentation. Anti-Abeta antibodies from
      our polymer-encapsulated vaccine were able to bind to A plaques in the brain of
      our mice, and were able to specifically recognize oligomeric Abeta. Our results
      suggest that the safety and efficacy issues previously encountered in other Abeta
      vaccination trials may be successfully addressed by using micelle-encapsulated
      peptides. These shorter Abeta fragments are also easier to synthesize and more
      cost-effective than the highly hydrophobic full-length Abeta1-42 peptide.

PMID- 29336539
TI  - Chitosan-Coated Poly(lactic-co-glycolic acid)-Diiodinated boron-Dipyrromethene
      Nanoparticles Improve Tumor Selectivity and Stealth Properties in Photodynamic
      Cancer Therapy.
AB  - Their limited solubility and lack of tumor selectivity limit the clinical
      usefulness of photosensitizers. Various nanostructures have been evaluated as
      delivery agents for photosensitizers in an attempt to overcome these obstacles,
      but these have typically been limited by premature clearance by the
      reticuloendothelial system (RES) and non-specific interactions with normal cells
      that result from their hydrophobic surfaces. In this study, we report our attempt
      to circumvent these problems by applying a low molecular weight chitosan (25 kDa)
      coating to a poly(lactic-co-glycolic acid)-diiodinated boron dipyrromethene (PLGA
      I2BODIPY) nanoparticle-photosensitizer construct. This chitosan coating increased
      the hydrophilicity and decreased the charge of PLGA-I2 BODIPY nanoparticle
      surfaces without changing their size (average diameter 147 nm) or morphology. In
      comparison to the uncoated controls, the coated nanoparticles reduced the burst
      release of I2BODIPY, increased its predominantly lysosomal cellular uptake, and
      enhanced its photocytotoxicity in 4T1 murine and MDA-MB-231 human breast cancer
      cells. PLGA-Chitosan-I2BODIPY nanoparticles also showed reduced serum protein
      adsorption and macrophage uptake compared to the uncoated controls. In 4T1 tumor
      bearing mice, the PLGA-Chitosan-I2BODIPY nanoparticles exhibited better tumor
      targeting selectivity and significantly reduced accumulation in RES tissues,
      including the lymph nodes, spleen and liver (by 10.2-, 2.1- and 1.3-fold,
      respectively), and in non-tumorous organs, such as the skin and eyes (by 22.7-
      and 4-fold, respectively). The PLGA-Chitosan-I2BODIPY and PLGA-I2BODIPY
      nanoparticles also showed increased anticancer efficacy compared to free
      I2BODIPY. These results suggest that the low molecular weight chitosan (25 kDa)
      is a promising nanoparticle "stealth coating" that improves tumor selectivity.

PMID- 29336540
TI  - Silicene on Monolayer PtSe2: From Strong to Weak Binding via NH3 Intercalation.
AB  - We study the properties of silicene on monolayer PtSe2 by first-principles
      calculations and demonstrate a much stronger interlayer interaction than
      previously reported for silicene on other semiconducting substrates. This fact
      opens the possibility of a direct growth. A band gap of 165 meV results from
      inversion symmetry breaking and large spin-splittings in the valence and
      conduction bands from proximity to monolayer PtSe2 and its strong spin-orbit
      coupling. It is also shown that the interlayer interaction can be effectively
      reduced by intercalating NH3 molecules between silicene and monolayer PtSe2
      without inducing charge transfer or defect states near the Fermi energy. A small
      NH3 diffusion barrier makes intercalation a viable experimental approach to
      control the interlayer interaction.

PMID- 29336541
TI  - Rapid Patterning of PDMS Microfluidic Device Wettability Using Syringe-Vacuum
      Induced Segmented Flow in Nonplanar Geometry.
AB  - We present a simple and rapid method to spatially pattern the surface wetting
      properties of PDMS microfluidic devices by layer-by-layer (LbL) deposition of
      polyelectrolytes using syringe-vacuum-induced segmented flow in nonplanar
      geometry. Our technique offers selective surface modification in microfluidic
      chips with multiple flow-focusing junctions, enabling production of monodisperse
      double- and triple-emulsion drops.

PMID- 29336542
TI  - Humidity-Sensing Performance of 3DOM WO3 with Controllable Structural
      Modification.
AB  - The development of humidity sensors with excellent sensing performance is a great
      challenge in the field of material chemistry. Here, we synthesized 3DOM WO3
      nanomaterials through a poly(methyl methacrylate) template method, and first, we
      applied it to humidity measurement. For the goal of better sensing performance,
      the structural modification of Li/K-codoping was adopted, and the test results
      showed that Li/K-codoped 3DOM WO3 possessed highly improved humidity sensing
      performances, such as high response, low-humidity hysteresis, good long-term
      stability, great repeatability, decent response, and recovery properties. To
      deeply understand the great effect of Li/K-codoping on sensing performance, the
      pure, Li-monodoped, and Li/K-codoped 3DOM WO3-based humidity sensors were
      compared, and we found that the structure defects and adsorbed oxygen as well as
      the co-effect of Li/K dopants were key factors for the improved sensing
      performance. Additionally, a possible humidity sensitive mechanism was proposed
      to further study the promotion effect of Li/K-codoping on humidity sensing
      process.

PMID- 29336543
TI  - Histone Deacetylase 11 Is a Fatty-Acid Deacylase.
AB  - Histone deacetylase 11 (HDAC11) is a sole member of the class IV HDAC subfamily
      with negligible intrinsic deacetylation activity. Here, we report in vitro
      profiling of HDAC11 deacylase activities, and our data unequivocally show that
      the enzyme efficiently removes acyl moieties spanning 8-18 carbons from the side
      chain nitrogen of the lysine residue of a peptidic substrate. Additionally, N
      linked lipoic acid and biotin are removed by the enzyme, although with lower
      efficacy. Catalytic efficiencies toward dodecanoylated and myristoylated peptides
      were 77 700 and 149 000 M-1 s-1, respectively, making HDAC11 the most proficient
      fatty-acid deacylase of the HDAC family. Interestingly, HDAC11 is strongly
      inhibited by free myristic, palmitic, and stearic acids with inhibition constants
      of 6.5, 0.9, and 1.6 MUM, respectively. At the same time, its deacylase activity
      is stimulated more than 2.5-fold by both palmitoyl-coenzyme A and myristoyl
      coenzyme A, pointing toward metabolic control of the enzymatic activity by fatty
      acid metabolites. Our data reveal novel enzymatic activity of HDAC11 that can, in
      turn, facilitate the uncovering of additional biological functions of the enzyme
      as well as the design of isoform-specific HDAC inhibitors.

PMID- 29336544
TI  - Identification of Collateral Sensitivity to Dihydroorotate Dehydrogenase
      Inhibitors in Plasmodium falciparum.
AB  - Drug resistance has been reported for every antimalarial in use highlighting the
      need for new strategies to protect the efficacy of therapeutics in development.
      We have previously shown that resistance can be suppressed with a population
      biology trap: by identifying situations where resistance to one compound confers
      hypersensitivity to another (collateral sensitivity), we can design combination
      therapies that not only kill the parasite but also guide its evolution away from
      resistance. We applied this concept to the Plasmodium falciparum dihydroorotate
      dehydrogenase ( PfDHODH) enzyme, a well validated antimalarial target with
      inhibitors in the development pipeline. Here, we report a high-throughput screen
      to identify compounds specifically active against PfDHODH resistant mutants. We
      additionally perform extensive cross-resistance profiling allowing us to identify
      compound pairs demonstrating the potential for mutually incompatible resistance.
      These combinations represent promising starting points for exploiting collateral
      sensitivity to extend the useful lifespan of new antimalarial therapeutics.

PMID- 29336545
TI  - Self-Assembly of Silicon@Oxidized Mesocarbon Microbeads Encapsulated in Carbon as
      Anode Material for Lithium-Ion Batteries.
AB  - The utilization of silicon/carbon composites as anode materials to replace the
      commercial graphite is hampered by their tendency to huge volumetric expansion,
      costly raw materials, and complex synthesis processes in lithium-ion batteries.
      Herein, self-assembly method is successfully applied to prepare hierarchical
      silicon nanoparticles@oxidized mesocarbon microbeads/carbon (Si@O-MCMB/C)
      composites for the first time, in which O-MCMB core and low-cost sucrose-derived
      carbon shell not only effectively enhance the electrical conductivity of the
      anode, but also mediate the dramatic volume change of silicon during cycles. At
      the same time, the carbon can act as "adhesive", which is crucial in enhancing
      the adhesive force between Si and O-MCMB in the composites. The as-obtained Si@O
      MCMB/C delivers an initial reversible capacity of 560 mAh g-1 at 0.1 A g-1, an
      outstanding cyclic retention of 92.8% after 200 cycles, and respectable rate
      capability. Furthermore, the synthetic route presented here is efficient, less
      expensive, simple, and easy to scale up for high-performance composites.

PMID- 29336546
TI  - CuAg@Ag Core-Shell Nanostructure Encapsulated by N-Doped Graphene as a High
      Performance Catalyst for Oxygen Reduction Reaction.
AB  - Development of a robust, cost-effective, and efficient catalyst is extremely
      necessary for oxygen reduction reaction (ORR) in fuel cell applications. Herein,
      we reported a well-defined nanostructured catalyst of highly dispersed CuAg@Ag
      core-shell nanoparticle (NP)-encapsulated nitrogen-doped graphene nanosheets
      (CuAg@Ag/N-GNS) exhibiting a superior catalytic activity toward ORR in alkaline
      medium. The synergistic effects produced from the unique properties of CuAg@Ag
      core-shell NPs and N-GNS made such a novel nanohybrid display a catalytic
      behavior comparable to that of the commercial Pt/C product. In particular, it
      demonstrated a much better stability and methanol tolerance than Pt/C under the
      same conditions. Because of its outstanding electrochemical performance and ease
      of synthesis, CuAg@Ag/N-GNS material was expected to be a promising low-cost
      catalyst for ORR in alkaline fuel cell applications.

PMID- 29336547
TI  - Efficient Blue and Yellow Organic Light-Emitting Diodes Enabled by Aggregation
      Induced Emission.
AB  - A new class of donor-bridge-acceptor (D-pi-A) pi-conjugated light-emitting
      molecules comprising carbazole as donor and maleimide (Cbz-MI, Cbz-MI(d)),
      phthalimide (Cbz-Pth) as acceptor units with phenyl ring as spacer have been
      synthesized in good yields. These compounds exhibit high quantum yield with three
      distinct emission colors yellowish-green (Cbz-MI), bright yellow Cbz-MI(d), and
      sky blue (Cbz-Pth) in the solid state. Single-crystal X-ray and quantum chemical
      calculations reveals that twisting of the phenyl rings with high torsional angle
      on maleimide and phthalimide units reduce the effective inter-chromophore
      electronic coupling, furnish dramatic changes in their photophysical properties
      in solution and solid states. Intriguingly, Cbz-MI(d) and Cbz-Pth exhibits a
      unique aggregation-induced blue-shifted emission (AIBSE) due to restricted
      intramolecular rotation (RIR) process, while Cbz-MI shows red-shifted emission in
      the solid state. The solvatochromic study reveal that combined RIR and excited
      state migration augment AIE (aggregation-induced emission) properties. The
      electrochemical properties reveal that Cbz-MI exhibits high oxidation propensity
      while Cbz-Pth shows low reduction values. Subsequently, organic light-emitting
      diodes (OLEDs) were fabricated with a simple three-layer device containing Cbz
      Pth and Cbz-MI(d) as emitting layers. Cbz-MI(d) exhibits high performance yellow
      OLED with an external quantum efficiency exceeding ~4.1% and a brightness
      exceeding ~73915 cd/m2, which is among the best performance reported for bright
      yellow fluorescence organic light-emitting diodes.

PMID- 29336548
TI  - Judicious Design of Cationic, Cyclometalated Ir(III) Complexes for Photochemical
      Energy Conversion and Optoelectronics.
AB  - The exponential growth in published studies on phosphorescent metal complexes has
      been triggered by their utilization in optoelectronics, solar energy conversion,
      and biological labeling applications. Very recent breakthroughs in organic
      photoredox transformations have further increased the research efforts dedicated
      to discerning the inner workings and structure-property relationships of these
      chromophores. Initially, the principal focus was on the Ru(II)-tris-diimine
      complex family. However, the limited photostability and lack of luminescence
      tunability discovered in these complexes prompted a broadening of the research to
      include 5d transition metal ions. The resulting increase in ligand field
      splitting prevents the population of antibonding eg* orbitals and widens the
      energy range available for color tuning. Particular attention was given to
      Ir(III), and its cyclometalated, cationic complexes have now replaced Ru(II) in
      the vast majority of applications. At the start, this Account documents the
      initial efforts dedicated to the color tuning of these complexes for their
      application in light emitting electrochemical cells, an easy to fabricate single
      layer organic light emitting device (OLED). Systematic modifications of the
      ligand sphere of [Ir(ppy)2bpy]+ (ppy: 2-phenylpyridine, bpy: 2,2'-bipyridine)
      with electron withdrawing and donating substituents allowed access to complexes
      with luminescence emission maxima throughout the visible spectrum exhibiting room
      temperature excited state lifetimes ranging from nanoseconds to dozens of
      microseconds and quantum yields up to 15 times that of [Ru(bpy)3]2+. The diverse
      photophysical properties were also beneficial when using these Ir(III) complexes
      for driving solar fuel-producing reactions. For instance, photocatalytic water
      reduction systems were explored to gain access to efficient water splitting
      systems. For this purpose, a variety of water reduction catalysts were paired
      with libraries of Ir(III) photosensitizers in high-throughput photoreactors. This
      parallelized approach allowed exploration of the interplay between the diverse
      photophysical properties of the Ir compounds and the electron-accepting
      catalysts. Further work enhanced and simplified the critical electron transfer
      processes between these two species through the use of bridging functional groups
      installed on the photosensitizer. Later, a novel approach summarized in this
      Account explores the possibility of using Zn metal as a solar fuel. Structure
      activity relationships of the light-driven reduction of Zn2+ to Zn metal are
      described. DFT calculations along with cyclic voltammetry were utilized to gain
      clear insights into the complexes' electronic structures responsible for the
      effective photochemical properties observed in these dyes. While [Ir(ppy)2bpy]+
      and its derivatives were found to be much more photostable than the Ru(II)-tris
      diimine complex family, mass spectrometry indicated that the bpy ligand still
      photodissociated under extensive illumination. An interesting new approach
      involved the substitution of the bidentate 2,2'-bipyridine with a stronger
      chelating terpyridine ligand. This approach leaves room for one 2-phenylpyridine
      ligand and a third, anionic ligand, either Cl- or CN-. This Account reviews the
      effect of structural modifications on the photophysical properties of these
      [Ir(tpy)(ppy)X]+ complexes and corroborates the findings with the results
      obtained through DFT modeling. These complexes found application in
      photocatalytic CO2 reductions as well as a solvent tolerant light-absorber for
      the photogeneration of hydrogen. It was also documented that the robustness of
      these dyes in photoredox processes supersedes those of the commercially available
      [Ir(ppy)2(dtbbpy)]PF6 and [Ir(dF(CF3)ppy)2(dtbbpy)]PF6 complexes pioneered in the
      Bernhard laboratory.

PMID- 29336549
TI  - Top-Down Hydrogen-Deuterium Exchange Analysis of Protein Structures Using
      Ultraviolet Photodissociation.
AB  - Top-down hydrogen-deuterium exchange (HDX) analysis using electron capture or
      transfer dissociation Fourier transform mass spectrometry (FTMS) is a powerful
      method for the analysis of secondary structure of proteins in solution. The
      resolution of the method is a function of the degree of fragmentation of backbone
      bonds in the proteins. While fragmentation is usually extensive near the N- and C
      termini, electron capture (ECD) or electron transfer dissociation (ETD)
      fragmentation methods sometimes lack good coverage of certain regions of the
      protein, most often in the middle of the sequence. Ultraviolet photodissociation
      (UVPD) is a recently developed fast-fragmentation technique, which provides
      extensive backbone fragmentation that can be complementary in sequence coverage
      to the aforementioned electron-based fragmentation techniques. Here, we explore
      the application of electrospray ionization (ESI)-UVPD FTMS on an Orbitrap Fusion
      Lumos Tribrid mass spectrometer to top-down HDX analysis of proteins. We have
      incorporated UVPD-specific fragment-ion types and fragment-ion mixtures into our
      isotopic envelope fitting software (HDX Match) for the top-down HDX analysis. We
      have shown that UVPD data is complementary to ETD, thus improving the overall
      resolution when used as a combined approach.

PMID- 29336550
TI  - Phasor-Fluorescence Lifetime Imaging Microscopy Analysis to Monitor Intercellular
      Drug Release from a pH-Sensitive Polymeric Nanocarrier.
AB  - The design of highly efficient drug carriers, and the development of appropriate
      techniques to monitor their mechanism of action and therapeutic effect, are both
      critical for improving chemotherapy. Herein, a polymeric nanoparticle, PAH
      Cit/DOX (poly(allylamine)-citraconic anhydride/doxorubicin), was synthesized and
      used as a nanodrug system for the efficient delivery and pH-responsive release of
      doxorubicin (DOX) into cancer cells. The PAH-Cit/DOX nanoparticles were stable at
      physiological pH but effectively released DOX under weakly acidic conditions. The
      release efficiency was 90.6% after 60 h of dialysis in phosphate-buffered saline
      at pH 5.5. Confocal images showed the rapid movement of the drug from the
      cytoplasm to the nucleus, indicating the effective drug release MCF-7 cells.
      Notably, the combination of fluorescence lifetime imaging microscopy (FLIM) and
      phasor analysis (phasor-FLIM) provides an approach to monitor the dynamic change
      of DOX fluorescence lifetime in intercellular environments. Phasor-differentiated
      lifetime pixel intensity in FLIM images was quantified and used to evaluate the
      DOX release from nanocarriers, making it possible to detect the dynamics of
      intracellular release and transport of DOX.

PMID- 29336551
TI  - First Gut Instincts Are Always Right: The Resolution Required for a Mass Defect
      Analysis of Polymer Ions Can Be as Low as Oligomeric.
AB  - Its recent adaptation to low-resolution mass spectra of polymers using fractional
      base units raises the question of the minimal resolution needed for a Kendrick
      mass defect (KMD) analysis. Intuiting an oligomeric resolution since the mass of
      a repeat unit is the sole value to be known, it is challenged by the relative
      failure of the KMD plots computed from an isotopically resolved matrix-assisted
      laser desorption ionization-time-of-flight (MALDI-TOF) mass spectrum to display
      clear alignments in the high mass range. Another procedure based on the
      remainders of Kendrick mass (RKMs) overcomes this pitfall with oligomers
      perfectly aligned in a new RKM plot. Despite a concomitant degradation of the
      resolving power and accuracy, with the example of MALDI-TOF/TOF mass spectra of a
      variety of homo- and copolymer ions, the RKM procedure still allows a rapid
      enumeration, assignment, and any further manipulation of all the product ion
      series in visual RKM plots. Successfully extended to the critical case of a MALDI
      mass spectrum recorded with a linear TOF analyzer allowing a bare oligomeric
      resolution, the RKM plot turns the distributions differing by their end-groups or
      adducted ion into clear horizontal lines. It eventually gives intuition its due
      by answering the original question: the minimal resolution required for a mass
      defect analysis can be as low as oligomeric with the appropriate formulas.

PMID- 29336552
TI  - Engineering the Surface of Therapeutic "Living" Cells.
AB  - Biological cells are complex living machines that have garnered significant
      attention for their potential to serve as a new generation of therapeutic and
      delivery agents. Because of their secretion, differentiation, and homing
      activities, therapeutic cells have tremendous potential to treat or even cure
      various diseases and injuries that have defied conventional therapeutic
      strategies. Therapeutic cells can be systemically or locally transplanted. In
      addition, with their ability to express receptors that bind specific tissue
      markers, cells are being studied as nano- or microsized drug carriers capable of
      targeted transport. Depending on the therapeutic targets, these cells may be
      clustered to promote intercellular adhesion. Despite some impressive results with
      preclinical studies, there remain several obstacles to their broader development,
      such as a limited ability to control their transport, engraftment, secretion and
      to track them in vivo. Additionally, creating a particular spatial organization
      of therapeutic cells remains difficult. Efforts have recently emerged to resolve
      these challenges by engineering cell surfaces with a myriad of bioactive
      molecules, nanoparticles, and microparticles that, in turn, improve the
      therapeutic efficacy of cells. This review article assesses the various
      technologies developed to engineer the cell surfaces. The review ends with future
      considerations that should be taken into account to further advance the quality
      of cell surface engineering.

PMID- 29336553
TI  - Catalytic Mechanism of Cruzain from Trypanosoma cruzi As Determined from Solvent
      Kinetic Isotope Effects of Steady-State and Pre-Steady-State Kinetics.
AB  - Cruzain, an important drug target for Chagas disease, is a member of clan CA of
      the cysteine proteases. Understanding the catalytic mechanism of cruzain is vital
      to the design of new inhibitors. To this end, we have determined pH-rate profiles
      for substrates and affinity agents and solvent kinetic isotope effects in pre
      steady-state and steady-state modes using three substrates: Cbz-Phe-Arg-AMC, Cbz
      Arg-Arg-AMC, and Cbz-Arg-Ala-AMC. The pH-rate profile of kcat/ Km for Cbz-Arg-Arg
      AMC indicated p K1 = 6.6 (unprotonated) and p K2 ~ 9.6 (protonated) groups were
      required for catalysis. The temperature dependence of the p K = 6.2-6.6 group
      exhibited a Delta Hion value of 8.4 kcal/mol, typical of histidine. The pH-rate
      profile of inactivation by iodoacetamide confirmed that the catalytic cysteine
      possesses a p Ka of 9.8. Normal solvent kinetic isotope effects were observed for
      both D2O kcat (1.6-2.1) and D2O kcat/ Km (1.1-1.4) for all three substrates. Pre
      steady-state kinetics revealed exponential bursts of AMC production for Cbz-Phe
      Arg-AMC and Cbz-Arg-Arg-AMC, but not for Cbz-Arg-Ala-AMC. The overall solvent
      isotope effect on kcat can be attributed to the solvent isotope effect on the
      deacylation step. Our results suggest that cruzain is unique among papain-like
      cysteine proteases in that the catalytic cysteine and histidine have neutral
      charges in the free enzyme. The generation of the active thiolate of the
      catalytic cysteine is likely preceded (and possibly triggered) by a ligand
      induced conformational change, which could bring the catalytic dyad into the
      proximity to effect proton transfer.

PMID- 29336554
TI  - Competition between Dehydrogenative Organometallic Bonding and Covalent Coupling
      of an Unfunctionalized Porphyrin on Cu(111).
AB  - We studied the formation of linked porphyrin oligomers from 5,15
      diphenylporphyrin (2H-DPP) by thermal, substrate-assisted organometallic and
      dehydrogenation coupling on Cu(111) by scanning tunneling microscopy. In the
      range of 300-620 K, we find three distinct stages, at 300 K, the intact 2H-DPP
      molecules self-assemble into linear structures held together by van der Waals
      forces. Increasing the substrate temperature, self-metalation and intramolecular
      ring-closing reactions result in planar and isolated DPP species on the surface.
      By C-H cleavage, porphyrin oligomers bonded by organometallic and covalent bonds
      between the modified DPP are formed. The amount of covalently bonded DPP
      oligomers increases strongly with annealing time and temperature, and they become
      the dominant species at 570 K. In contrast, the number of organometallically
      bonded DPP oligomers increases moderately even up to 620 K, indicating that in
      this case the organometallic bond is no precursor of the covalent bond.

PMID- 29336555
TI  - Correction to Ozone Formation Induced by the Impact of Reactive Bromine and
      Iodine Species on Photochemistry in a Polluted Marine Environment.

PMID- 29336556
TI  - Linking Spectral Induced Polarization (SIP) and Subsurface Microbial Processes:
      Results from Sand Column Incubation Experiments.
AB  - Geophysical techniques, such as spectral induced polarization (SIP), offer
      potentially powerful approaches for in situ monitoring of subsurface
      biogeochemistry. The successful implementation of these techniques as monitoring
      tools for reactive transport phenomena, however, requires the deconvolution of
      multiple contributions to measured signals. Here, we present SIP spectra and
      complementary biogeochemical data obtained in saturated columns packed with
      alternating layers of ferrihydrite-coated and pure quartz sand, and inoculated
      with Shewanella oneidensis supplemented with lactate and nitrate. A biomass
      explicit diffusion-reaction model is fitted to the experimental biogeochemical
      data. Overall, the results highlight that (1) the temporal response of the
      measured imaginary conductivity peaks parallels the microbial growth and decay
      dynamics in the columns, and (2) SIP is sensitive to changes in microbial
      abundance and cell surface charging properties, even at relatively low cell
      densities (<108 cells mL-1). Relaxation times (tau) derived using the Cole-Cole
      model vary with the dominant electron accepting process, nitrate or ferric iron
      reduction. The observed range of tau values, 0.012-0.107 s, yields effective
      polarization diameters in the range 1-3 MUm, that is, 2 orders of magnitude
      smaller than the smallest quartz grains in the columns, suggesting that
      polarization of the bacterial cells controls the observed chargeability and
      relaxation dynamics in the experiments.

PMID- 29336557
TI  - Nitrosoallene-Mediated endo-Cyclizations for the Synthesis of (Hetero)cyclic
      alpha-Substituted exo-Unsaturated Oximes.
AB  - Nitrosoallene-mediated endo-dig cyclization reactions producing (hetero)cyclic
      exo-unsaturated oximes (enoximes) are described. The intramolecular 1,4-type
      addition to in situ generated nitrosoallenes afforded alpha-substituted cyclic
      enoximes with exo-methylene units, which are the favored conformation for further
      cyclizations. The strong electron-withdrawing ability of the nitroso group
      facilitated the construction of five-to-seven-membered ring systems via C-O, C-N,
      C-S, and C-C bond formations, including a quaternary carbon center, at low
      temperatures.

PMID- 29336558
TI  - Excited-State Processes of Cyclometalated Platinum(II) Charge-Transfer Dimers
      Bridged by Hydroxypyridines.
AB  - A series of four anti-disposed dinuclear platinum(II) complexes featuring metal
      metal-to-ligand charge-transfer (MMLCT) excited states, bridged by either 2
      hydroxy-6-methylpyridine or 2-hydroxy-6-phenylpyridine and cyclometalated with
      7,8-benzoquinoline or 2-phenylpyridine, are presented. The 2-hydroxypyridine
      bridging ligands control intramolecular d8-d8 metal-metal sigma interactions,
      affecting the frontier orbitals' electronic structure, resulting in marked
      changes to the ground- and excited-state properties of these complexes. Three of
      these molecules possess reversible one-electron oxidations in cyclic voltammetry
      experiments as a result of strong intramolecular metallophilic interactions. In
      this series of molecules, X-ray crystallography revealed Pt-Pt distances ranging
      between 2.815 and 2.878 A; the former represents the shortest reported metal
      metal distance for platinum(II) dimers possessing low-energy MMLCT transitions.
      All four molecules reported here display visible absorption bands beyond 500 nm
      and feature MMLCT-based red photoluminescence (PL) above 700 nm at room
      temperature with high PL quantum yields (up to 4%) and long excited-state
      lifetimes (up to 341 ns). The latter were recorded using both transient PL and
      transient absorption experiments that self-consistently yielded quantitatively
      identical excited-state lifetimes. The energy-gap law was successfully applied to
      this series of chromophores, documenting this behavior for the first time in
      molecules possessing MMLCT excited states. The combined data illustrate that
      entirely new classes of MMLCT chromophores can be envisioned using bridging
      pyridyl hydroxides in cooperation with various C^N cyclometalates to achieve
      photophysical properties suitable for excited-state electron- and energy-transfer
      chemistry.

PMID- 29336559
TI  - Investigation on Two Forms of Temperature-Sensing Parameters for Fluorescence
      Intensity Ratio Thermometry Based on Thermal Coupled Theory.
AB  - Absolute temperature sensitivity (Sa) reflects the precision of sensors that
      belong to the same mechanism, whereas relative temperature sensitivity (Sr) is
      used to compare sensors from different mechanisms. For the fluorescence intensity
      ratio (FIR) thermometry based on two thermally coupled energy levels of one rare
      earth (RE) ion, we define a new ratio as the temperature-sensing parameter that
      can vary greatly with temperature in some circumstances, which can obtain higher
      Sa without changing Sr. Further discussion is made on the conditions under which
      these two forms of temperature-sensing parameters can be used to achieve higher
      Sa for biomedical temperature sensing. Based on the new ratio as the temperature
      sensing parameter, the Sa and Sr of the BaTiO3: 0.01%Pr3+, 8%Yb3+ nanoparticles
      at 313 K reach as high as 0.1380 K-1 and 1.23% K-1, respectively. Similarly, the
      Sa and Sr of the BaTiO3: 1%Er3+, 3%Yb3+ nanoparticles at 313 K are as high as
      0.0413 K-1 and 1.05% K-1, respectively. By flexibly choosing the two ratios as
      the temperature-sensing parameter, higher Sa can be obtained at the target
      temperature, which means higher precision for the FIR thermometers.

PMID- 29336560
TI  - Trifluoromethyl-Substituted Iridium(III) Complexes: From Photophysics to
      Photooxidation of a Biological Target.
AB  - Photodynamic therapeutic agents are of key interest in developing new strategies
      to develop more specific and efficient anticancer treatments. In comparison to
      classical chemotherapeutic agents, the activity of photodynamic therapeutic
      compounds can be finely controlled thanks to the light triggering of their
      photoreactivity. The development of type I photosensitizing agents, which do not
      rely on the production of ROS, is highly desirable. In this context, we developed
      new iridium(III) complexes which are able to photoreact with biomolecules;
      namely, our Ir(III) complexes can oxidize guanine residues under visible light
      irradiation. We report the synthesis and extensive photophysical characterization
      of four new Ir(III) complexes, [Ir(ppyCF3)2(N^N)]+ [ppyCF3 = 2-(3,5
      bis(trifluoromethyl)phenyl)pyridine) and N^N = 2,2'-dipyridyl (bpy); 2-(pyridin-2
      yl)pyrazine (pzpy); 2,2'-bipyrazine (bpz); 1,4,5,8-tetraazaphenanthrene (TAP)].
      In addition to an extensive experimental and theoretical study of the
      photophysics of these complexes, we characterize their photoreactivity toward
      model redox-active targets and the relevant biological target, the guanine base.
      We demonstrate that photoinduced electron transfer takes place between the
      excited Ir(III) complex and guanine which leads to the formation of stable
      photoproducts, indicating that the targeted guanine is irreversibly damaged.
      These results pave the way to the elaboration of new type I photosensitizers for
      targeting cancerous cells.

PMID- 29336561
TI  - A Borane Platinum Complex Undergoing Reversible Hydride Migration in Solution.
AB  - Reaction of [Pt(kappa2-C,N-ppy)(dmso)Cl], 1 (Hppy = 2-phenylpyridine), with
      Na[H2B(mb)2] (Hmb = 2-mercapto-benzimidazole) smoothly afforded the complex
      {[(kappa3-S,B,S-HB(mb)2]Pt(kappa2-C,N-ppy)H}, 2, featuring a strong reverse
      dative Pt -> B sigma interaction in the solid state. When dissolved in thf (or
      acetone) solution, 2 undergoes a reversible Pt-H bond activation, establishing an
      equilibrium between the hexacoordinated 2 and the tetracoordinate complex
      {[(kappa2-S,S-H2B(mb)2]Pt(kappa2-C,N-ppy)}, 3, as ascertained by multinuclear
      NMR. Hydrolysis of the B-N bond in 2/3 resulted ultimately in the formation of a
      dimeric half-lantern platinum(II,II) complex [{Pt(kappa2-C,N-ppy)(MU2-kappa2-N,S
      mb)}2], 4. The SC-XRD structures of 2 and 4 are reported.

PMID- 29336562
TI  - Neutron Diffraction Study on the Structure of Hydrated Li+ in Dilute Aqueous
      Solutions.
AB  - Neutron diffraction measurements have been carried out for 6Li/7Li isotopically
      substituted aqueous 1.0 mol % (0.5 mol/kg) LiCl and 1.1 mol % (0.56 mol/kg)
      LiClO4 solutions in D2O to obtain structural insight concerning hydration
      structure of Li+ in more dilute electrolyte solutions. The first-order difference
      function, DeltaLi(Q), was analyzed by means of the least squares fitting
      procedure to obtain short-range structural parameters around the Li+. It was
      revealed that the nearest neighbor Li+...O(D2O) distance, rLiO, and the
      coordination number, nLiO, for the aqueous 1.0 mol % LiCl solution are 2.01 +/-
      0.02 A and 5.9 +/- 0.1, respectively. The values, rLiO = 1.97 +/- 0.02 A and nLiO
      = 6.1 +/- 0.1, are obtained for aqueous 1.1 mol % LiClO4 solution. These results
      indicate that the hydration number of Li+ in a dilute solution is close to 6,
      which is much larger than 4, which has long been believed. A possible explanation
      is that the hydration number of Li+ varies with the solute concentration.

PMID- 29336563
TI  - Electron Precise Group 5 Dimetallaheteroboranes [{CpV(MU-EPh)}2{MU-eta2:eta2
      BH3E}] and [{CpNb(MU-EPh)}2{MU-eta2:eta2-B2H4E}] (E = S or Se).
AB  - Synthesis and structural elucidation of various electron precise group 5
      dimetallaheteroboranes have been described. Room temperature reaction of
      [Cp2VCl2] with Li[BH3(EPh)], generated from the treatment of LiBH4.THF and Ph2E2
      (E = S or Se), for 1 h in toluene, followed by thermolysis, led to the formation
      of bimetallic complexes [{CpV(MU-EPh)}2{MU-eta2:eta2-BH3E}], 1 and 2 (1: E = S
      and 2: E = Se), and [{CpV(MU-SePh)}2{MU-eta2:eta2-BH(OC4H8)Se}], 3. One of the
      striking features of these compounds is that they represent a rare class of
      distorted tetrahedral clusters having bridging hydrogens. Evaluating the skeletal
      electron pairs and bonding types, compounds 1, 2, and 3 may be considered as
      isoelectronic with our earlier reported [(CpV)2(B2H6)2]. In an attempt to
      synthesize the Nb analogues of 1-3, room temperature reactions of [CpNbCl4] and
      Li[BH3(EPh)] (E = S or Se) were carried out that afforded compounds [{CpNb(MU
      EPh)}2{MU-eta2:eta2-B2H4E}], 4 and 5 (4: E = S and 5: E = Se). The solid-state X
      ray structures of both 4 and 5 exemplify electronically saturated [M2B3] systems,
      and their geometries are analogous to that of [(Cp*MoCl)2B3H7]. For the extension
      of this work, reaction of [Cp*TaCl4] (Cp* = eta5-C5Me5) with Li[BH3(SePh)] was
      carried out that yielded a tantalaselenaborane cluster [(Cp*Ta)2(MU
      Se)B3H6Se(C6H5)] (6). All the new compounds have been characterized using 1H,
      11B{1H}, 13C{1H} NMR, UV-vis absorption, and IR spectroscopy, mass spectrometry,
      and X-ray diffraction studies.

PMID- 29336564
TI  - Benzophenone-4 Promotes the Growth of a Pseudomonas sp. and Biogenic Oxidation of
      Mn(II).
AB  - Interactions between microbes and micropollutants (MPs) play a crucial role in
      water purification or treatment. Current studies have generally focused on the
      direct degradation or cometabolism of MPs. Considering the increasing interest in
      and importance of the roles of MPs in microbial metabolism, we adopted an Mn(II)
      oxidizing Pseudomonas sp. QJX-1 using tyrosine (Tyr) as the sole carbon and
      nitrogen source to investigate the effects of seven MPs on its growth and
      function. Six MPs exhibited an inhibition effect on bacterial growth and Mn(II)
      oxidation. Only benzophenone-4 (BP-4) promoted the growth of QJX-1 and biogenic
      oxidation Mn(II), but its concentration was not directly coupled to growth, which
      was unexpected. RNA-seq data suggested that the addition of BP-4 did not
      significantly change the basic metabolic function of QJX-1, but stimulated the
      upregulation of the pyruvate and gluconeogenesis metabolic pathways of Tyr for
      QJX-1 growth. Furthermore, protein identification and extracellular superoxide
      detection indicated that Mn(II) oxidation was largely driven by the formation of
      superoxide in response to Tyr starvation; the acceleration of superoxide
      production, due to BP-4 accelerating Tyr consumption, was responsible for the
      promotion effect of BP-4 on QJX-1 Mn(II) oxidation. Our findings highlight the
      dual effects that MPs can have on the growth and function of a single strain in
      aquatic ecosystem, i.e., the coexistence of inhibition and promotion.

PMID- 29336565
TI  - Appearances of Fukushima Daiichi Nuclear Power Plant-Derived 137Cs in Coastal
      Waters around Japan: Results from Marine Monitoring off Nuclear Power Plants and
      Facilities, 1983-2016.
AB  - Monitoring of 137Cs in seawater in coastal areas around Japan between 1983 and
      2016 yielded new insights into the sources and transport of Fukushima Daiichi
      Nuclear Power Plant (FDNPP)-derived 137Cs, particularly along the west coast of
      Japan. Before the FDNPP accident (1983-2010), the activity concentrations of
      137Cs, mainly from fallout, were decreasing exponentially. Effective 137Cs half
      lives in surface seawater ranged from 15.6 to 18.4 yr. After the FDNPP accident
      (March 2011) 137Cs activity concentrations in seawater off Fukushima and
      neighboring prefectures immediately increased. Since May/June 2011, 137Cs
      activity concentrations there have been declining, and they are now approaching
      preaccident levels. Along the west coast of Japan remote from FDNPP (i.e., the
      Japan Sea), however, radiocesium activity concentrations started increasing by
      2013, with earlier (May/June 2011) increases at some sites due to airborne
      transport and fallout. The inventory of 137Cs in the Japan Sea (in the main body
      of the Tsushima Warm Current) in 2016 was calculated to be 0.97 * 1014 Bq,
      meaning that 0.44 * 1014 Bq of FDNPP-derived 137Cs was added to the estimated
      global fallout 137Cs inventory in 2016 (0.53 * 1014 Bq). The net increase of
      137Cs inventory in the Japan Sea through the addition of FDNPP-derived 137Cs
      accounts for approximately 0.2% of the total 137Cs flux from the plant to the
      ocean from the accident.

PMID- 29336566
TI  - Electrochemistry of Bis(pyridine)cobalt (Nitrophenyl)corroles in Nonaqueous
      Media.
AB  - A series of bis(pyridine)cobalt corroles with one or three nitrophenyl groups on
      the meso positions of the corrole macrocycle were synthesized and characterized
      as to their electrochemical and spectroscopic properties in dichloromethane,
      benzonitrile, and pyridine. The potentials for each electrode reaction were
      measured by cyclic voltammetry and the electron-transfer mechanisms evaluated by
      analysis of the electrochemical data combined with UV-visible spectra of the
      neutral, electroreduced, and electroxidized forms of the corroles. The proposed
      electronic configurations of the initial compounds and the prevailing redox
      reactions involving the electroactive central cobalt ion, the electroactive
      conjugated macrocycle, and the electroactive meso-nitrophenyl groups are all
      discussed in terms of solvent binding and the number of the nitrophenyl groups
      and other substituents on the meso-nitrophenyl rings of the compounds.

PMID- 29336567
TI  - Nonisothermal Spreading Dynamics of Self-Rewetting Droplets.
AB  - We experimentally studied the spreading dynamics of binary alcohol mixtures (and
      pure liquids for reference) deposited on a heated substrate in a partially
      wetting situation under nonisothermal conditions. We show that the spreading
      mechanism of an evaporating droplet exhibits a power-law growth with early-stage
      exponents that depend strongly and nonmonotonically on the substrate temperature.
      Moreover, we investigated the temporal and spatial thermal dynamics in the
      droplet using infrared thermography, revealing the existence of unique thermal
      patterns due to thermal and/or solutal instabilities, which lead to surface
      tension gradients, namely the Marangoni effect. Our key findings are that the
      temperature of the substrate drastically affects the early-stage inertial
      capillary spreading regime owing to the nonmonotonic surface tension-temperature
      dependence of the self-rewetting liquids. At later stages of wetting, the
      spreading dynamics enters the viscous-capillary dominated regime, with the
      characteristic low kinetics mirroring the behavior of pure liquids.

PMID- 29336569
TI  - Paper-Based DNA Reader for Visualized Quantification of Soil-Transmitted Helminth
      Infections.
AB  - Soil-transmitted helminth (STH) infections are a global health issue affecting
      nearly one-third of the world's population. As most endemic areas of STH are
      impoverished countries or regions with limited healthcare resources, the accurate
      diagnosis of STH requires analytical tools that are not only quantitative, but
      also portable, inexpensive, and with no or minimal demand for external
      instrument. Herein, we introduce a novel paper-based diagnostic device, termed
      quantitative paper-based DNA reader (qPDR), capable of quantifying STH at the
      molecular level by measuring distance as readout, thus eliminating the need for
      external readers. On the basis of the unique interfacial interaction of a DNA
      intercalating dye, SYBR Green I, with native cellulose on a chromatographic
      paper, qPDR allows the distance-based quantification of minute amounts of double
      stranded DNA as short as 6 min. By integrating qPDR with polymerase chain
      reactions that were performed using a smartphone-controlled portable thermal
      cycler, we were able to quantify minute amount of genetic markers from adult
      worms of an STH (Trichuris trichiura) that were expelled post-treatment by
      infected children living in the rural areas of Honduras.

PMID- 29336568
TI  - Strain Distribution Across an Individual Shear Band in Real and Simulated
      Metallic Glasses.
AB  - Because of the fast dynamics of shear band formation and propagation along with
      the small size and transient character of the shear transformation zones (STZs),
      the elementary units of plasticity in metallic glasses, the description of the
      nanoscale mechanism of shear banding often relies on molecular dynamics (MD)
      simulations. However, the unrealistic parameters used in the simulations related
      to time constraints may raise questions about whether quantitative comparison
      between results from experimental and computational analyses is possible. Here,
      we have experimentally analyzed the strain field arising across an individual
      shear band by nanobeam X-ray diffraction and compared the results with the strain
      characterizing a shear band generated by MD simulations. Despite their largely
      different spatiotemporal scales, the characteristic features of real and
      simulated shear bands are strikingly similar: the magnitude of the strain across
      the shear band is discontinuous in both cases and the direction of the principal
      strain axes exhibits the same antisymmetric profile. This behavior can be
      explained by considering the mechanism of STZ activation and percolation at the
      nanoscale, indicating that the nanoscale effects of shear banding are not limited
      to the area within the band but they extend well into the surrounding elastic
      matrix. These findings not only demonstrate the reliability of MD simulations for
      explaining (also quantitatively) experimental observations of shear banding but
      also suggest that designed experiments can be used the other way around to verify
      numerical predictions of the atomic rearrangements occurring within a band.

PMID- 29336570
TI  - Design of Near-Infrared Luminescent Lanthanide Complexes Sensitive to
      Environmental Stimulus through Rationally Tuning the Secondary Coordination
      Sphere.
AB  - The design of near-infrared (NIR) emissive lanthanide (Ln) complexes sensitive to
      external stimulus is fundamentally important for the practical application of Ln
      materials. Because NIR emission from Ln is extremely sensitive to X-H (X = C, N
      and O) bond vibration, we herein report to harness the secondary coordination
      sphere to design NIR luminescent lanthanide sensors. Toward this goal, we
      designed and synthesized two isomeric [(eta5-C5H5)Co{(D3CO)2P = O}3]-Yb(III)
      7,8,12,13,17,18-hexafluoro-5,10,15,20-tetrakis(pentafluorophenyl)porpholactol NIR
      emitters, Yb-up and Yb-down, based on the stereoisomerism of porphyrin peripheral
      beta-hydroxyl group. Yb-up, in which beta-OH is at the same side of Yb(III)
      center, can form an intramolecular hydrogen bond with the axial Klaui ligand,
      whereas Yb-down cannot because its beta-OH is opposite to Yb(III) center. X-ray
      crystal structures and photophysical studies suggested that the intramolecular
      hydrogen bond plays important roles on the NIR luminescence of ytterbium(III),
      which shortens the distance between beta-OH and Yb(III) and facilitates the
      nonradiative deactivation of Ln excited state. Importantly, Yb-up/down were
      demonstrated to be highly sensitive toward temperature and viscosity. The PMMA
      polymer using Yb-up as the dopant NIR emitter showed thermosensitivity up to 6.0%
      degrees C-1 in the wide temperature range of 77-400 K, higher than that of Yb
      down (3.8%  degrees C-1). These complexes were also explored as the first NIR
      viscosity sensor, revealing their potential applications as optical sensors
      without visible light interference. This work demonstrates the importance of
      secondary coordination sphere on designing NIR Ln luminescent functional
      materials.

PMID- 29336571
TI  - Atmospheric Processing and Iron Mobilization of Ilmenite: Iron-Containing Ternary
      Oxide in Mineral Dust Aerosol.
AB  - Over the last several decades, iron has been identified as a limiting nutrient in
      about half of the world's oceans. Its most significant source is identified as
      deposited iron-containing mineral dust that has been processed during atmospheric
      transportation. The current work focuses on chemical and photochemical processing
      of iron-containing mineral dust particles in the presence of nitric acid, and an
      organic pollutant dimethyl sulfide under atmospherically relevant conditions.
      More importantly, ilmenite (FeTiO3) is evaluated as a proxy for the iron
      containing mineral dust. The presence of titanium in its lattice structure
      provides higher complexity to mimic mineral dust, yet it is simple enough to
      study reaction pathways and mechanisms. Here, spectroscopic methods are combined
      with dissolution measurements to investigate atmospheric processing of iron in
      mineral dust, with specific focus on particle mineralogy, particle size, and
      their environmental conditions (i.e., pH and solar flux). Our results indicate
      that the presence of titanium elemental composition enhances iron dissolution
      from mineral dust, at least by 2-fold comparison with its nontitanium-containing
      counterparts. The extent of iron dissolution and speciation is further influenced
      by the above factors. Thus, our work highlights these important, yet
      unconsidered, factors in the atmospheric processing of iron-containing mineral
      dust aerosol.

PMID- 29336572
TI  - {[Hg(SCN)3]2(MU-L)}2-: An Efficient Secondary Building Unit for the Synthesis of
      2D Iron(II) Spin-Crossover Coordination Polymers.
AB  - We report an unprecedented series of two-dimensional (2D) spin-crossover (SCO)
      heterobimetallic coordination polymers generically formulated as
      {FeII[(HgII(SCN)3)2](L)x}.Solv, where x = 2 for L = tvp (trans-(4,4'
      vinylenedipyridine)) (1tvp), bpmh ((1E,2E)-1,2-bis(pyridin-4
      ylmethylene)hydrazine) (1bpmh.nCH3OH; n = 0, 1), bpeh ((1E,2E)-1,2-bis(1-(pyridin
      4-yl)ethylidene)hydrazine) (1bpeh.nH2O; n = 0, 1) and x = 2.33 for L = bpbz (1,4
      bis(pyridin-4-yl)benzene) (1bpbz.nH2O; n = 0, 2/3). The results confirm that self
      assembly of FeII, [HgII(SCN)4]2-, and ditopic rodlike bridging ligands L
      containing 4-pyridyl moieties favors the formation of linear [Fe(MU-L)]n2n+
      chains and in situ generated binuclear units {[HgII(SCN)3]2(MU-L)}2-. The latter
      act as bridges between adjacent chains generating robust 2D layers. The [FeIIN6]
      centers are equatorially surrounded by four NCS- groups and two axial N atoms of
      the organic ligand L. The compound 1tvp and the unsolvated form of 1bpmh undergo
      complete SCO centered at T1/2 = 177 and 226 K, characterized by the enthalpy and
      entropy variations DeltaH = 12.3 and 10.5 kJ mol-1 and DeltaS = 69.4 and 48 J K-1
      mol-1, respectively. The almost complete SCO of the unsolvated form of 1bpeh
      occurs at ca. T1/2 = 119 K and exhibits a complete LIESST effect. Regardless of
      the degree of solvation, a half-spin conversion at T1/2 < 100 K occurs for
      1bpbz.nH2O, which becomes almost complete at p = 0.65 GPa. The labile solvent
      molecules present in 1bpmh.CH3OH and 1bpeh.H2O have a dramatic influence on the
      corresponding SCO behavior.

PMID- 29336573
TI  - Biomimetic Enantioselective Total Synthesis of (-)-Petromindole.
AB  - The first enantioselective total synthesis of (-)-petromindole, an
      architecturally distinct congener of indole diterpene family, has been achieved.
      Key features of this synthetic route include the scalable and concise synthesis
      of tricyclic allylic alcohol from enantiopure Wieland-Mischer ketone derivative,
      and TMSOTf-mediated, highly efficient biomimetic C-4 cyclization of indole
      derivative for the rapid construction of a hexacyclic skeleton of petromindole.

PMID- 29336574
TI  - Janus-Type Gold/Polythiophene Composites Formed via Redox Reaction at the Ionic
      Liquid|Water Interface.
AB  - Janus-type Au/polythiophene (PT) composites have been prepared by utilizing the
      liquid/liquid interface between water (W) and a hydrophobic ionic liquid (IL) as
      the redox reaction site. AuCl4- is reductively deposited, and terthiophene is
      oxidatively polymerized spacio-selectively at the IL|W interface, leading to the
      formation of the Au/PT composites. The composites are Janus-type Au-attached PT
      plates with two surface morphologies, flat surface and flowerlike surface at the
      W and IL sides of the plates at the IL|W interface, respectively. Not only
      surface morphologies but also attached Au structures are different at the two
      surfaces; Au microurchins on the flat surface and dendritic Au nanofibers on the
      flowerlike surface. Optical and scanning electron microscopic observations have
      revealed that nanofibers and microurchins are formed at the early and later stage
      of the reaction, respectively. Electrochemistry at the IL|W interface has
      illustrated that electron transfer across the IL|W interface during the formation
      of the Janus-type Au/PT composites is coupled with ion transfer of AuCl4- to
      compensate for the charge unbalance in the two liquid phases. AuCl4- transferred
      into IL is found to be the source of the dendritic Au nanofibers formed at the IL
      side of the PT plates.

PMID- 29336576
TI  - Dicyclopentyl Dithiosquarate as an Intermediate for the Synthesis of
      Thiosquaramides.
AB  - A general and greatly improved route is reported for the synthesis of a variety
      of thiosquaramides from a common dithionated intermediate. Both diaryl
      thiosquaramides and bifunctional thiosquaramides are readily accessed from
      dicyclopentyl dithiosquarate via two addition-elimination reactions. The
      convenient handling characteristics and relative stability of associated
      intermediates enable an operationally simple thiosquaramide preparation.
      Bifunctional aryl thiosquaramides, which were inaccessible by the previous
      method, are also prepared, and their catalytic performance is demonstrated,
      including their capability to function as Bronsted acid catalysts.

PMID- 29336577
TI  - [Indications to liver transplantation].
AB  - Liver transplantation should be considered in patients with end-stage liver
      disease in whom this operation would extend life expectancy beyond what the
      natural history of underlying disease would predict or in whom transplantation is
      likely to substantially improve the quality of life. Liver transplantation is
      indicated in end-stage liver disease, in selected liver tumors and in fulminant
      liver failure. The most common indication in adult to transplantation is
      decompensated liver cirrhosis with life expectancy one year or less. Evaluation
      and referral to transplantation center should be considered when a major
      complication of liver cirrhosis occurs - ascites, bleeding due to portal
      hypertension, hepatorenal syndrome or hepatic encephalopathy. MELD score 15 is
      recommended to list patients with end-stage liver disease. In recent years the
      indication of decompensated cirrhosis B and C is declining, on contrary, there is
      an increase in indication for hepatocellular carcinoma and NASH. An extension of
      indications has been observed recently - patients above 70 years of age, patients
      with neuroendocrine tumors among others. In 2016 in Czech Republic total 179
      livers were transplanted, but only a small fraction of potential candidates was
      referred to transplant centers.

PMID- 29336575
TI  - Challenges in the Conversion of Manual Processes to Machine-Assisted Syntheses:
      Activation of Thioglycoside Donors with Aryl(trifluoroethyl)iodonium Triflimide.
AB  - The steps needed to adapt a stable iodonium promoter for use in automated
      fluorous-assisted solution-phase oligosaccharide synthesis are described. Direct
      adaptation of the originally reported batch procedure resulted in the formation
      of an orthoester or protecting group transfer to the glycosyl acceptor.
      Fortunately, the addition of inexpensive beta-pinene as an acid scavenger avoided
      both of these side reactions. The utility of this newly developed protocol was
      applied to the automated solution-phase synthesis of a beta-glucan fragment.

PMID- 29336578
TI  - [Intestinal transplantation in Czech Republic].
AB  - : Intestinal transplantation represents a suitable treatment for patients with
      intestinal failure who then develop life-threatening complications of total
      parenteral nutrition and for some patients with complex abdominal disorders not
      suitable for conventional treatment. METHODS: prior to launch of the clinical
      program, preparation started in 2006 initially with extensive experimentation
      carried out on pigs. The clinical phase involved a specialized, multidisciplinary
      team who examined 23 patients being considered for transplantation. Seven
      patients were put on a waiting list and one female, due to the improvement of her
      medical status, was unlisted. The first ever intestinal transplantation was done
      in 2014. RESULTS: three out of six transplanted patients are alive with 380 days
      of actual survival; median 131 days (63-763). Two patients are on a full oral
      diet and nutritionally independent with an excellent quality of life. One female
      is nutritionally independent but with the need for partial supplemental
      parenteral rehydration due to the stomal output. CONCLUSION: intestinal
      transplantation is a suitable treatment for highly selected patients with
      intestinal failure who meet specific listing criteria.

PMID- 29336579
TI  - [Pros and cons of dual kidney transplantation].
AB  - Dual kidney transplantation is one of the options to utilize so called marginal
      grafts, kidneys that would be insufficient for normal single transplantation.
      This time consuming and burdensome surgical procedure can be beneficial in
      precisely selected patients. This method requires correct algorithm of donors and
      recipients selections, than we can expect the best results.Key words: dual kidney
      transplantation, marginal donor, chronic renal failure, expanded criteria donor.

PMID- 29336580
TI  - Organ transplantation from donors after circulatory death.
AB  - The scarcity of organs for transplantation resulted in the increase of organ
      donation after circulatory death. This review describes the current practice with
      donors after circulatory death (DCD), recent classification of DCD and organ
      procurement from DCD. Then the outcome of organ transplantation from is discussed
      and the new strategies in DCD are presented. Despite of the fact that DCD are
      extended criteria donors, strict organ selection and novel technologies as
      machine perfusion or normothermic perfusion allows better utilization of DCD with
      a similar outcome as from donors after brain death.

PMID- 29336581
TI  - [Organ transplantation from donors after circulatory death].
AB  - The scarcity of organs for transplantation resulted in the increase of organ
      donation after circulatory death. This review describes the current practice with
      donors after circulatory death (DCD), recent classification of DCD and organ
      procurement from DCD. Then the outcome of organ transplantation from is discussed
      and the new strategies in DCD are presented. Despite of the fact that DCD are
      extended criteria donors, strict organ selection and novel technologies as
      machine perfusion or normothermic perfusion allows better utilization of DCD with
      a similar outcome as from donors after brain death.

PMID- 29336582
TI  - [Psychological evaluation of uterus transplantation trial participants].
AB  - Uterus transplantation is a life-giving and quality-of-life enhancing
      transplantation. Life with transplanted uterus is a transitional phase of life
      for both recipients and their partners. Six deliveries of healthy children from
      five transplanted mothers out of 9 uterus transplantations in Sweden may
      encourage untimely hopes of thousands of women with absolute uterine factor
      infertility worldwide. Psychological evaluation might be included into all trials
      regarding new treatment methods and treatment procedures. Main psychological
      issues connected with the infertility treatment in women with absent uterus are
      clearly defined (especially in vitro fertilization, uterus transplantation,
      compliance with immunosuppressive treatment, ultrasound examinations of uterine
      vascular perfusion, rejection signs surveillance, embryo transfer, pregnancy,
      cesarean section, preterm delivery risk, puerperium, hysterectomy and
      immunosuppressive treatment termination). The role of psychological evaluation of
      participants before the admission to complicated treatment process is to choose
      those who will be able to cope all mentioned difficulties and unexpected
      complications including potential failure of the whole treatment without serious
      negative impact on their psychological situation. Up to now experience with
      psychological stability of our 7 uterus recipients and 3 uterus living donors are
      good although post-transplant period is especially in recipients connected with
      everyday psychological adaptation on the significant life changes. We are aware
      that psychological evaluation of our study participants will require further 3
      years of follow up with publication of our results.

PMID- 29336583
TI  - [Psychological problems of patients who survived cardiac arrest out of hospital].
AB  - Out-of-hospital circulatory arrest is a major challenge of current medicine.
      Circulatory arrest survivors bear increased risk of developing anxiety disorders
      and depressions both during hospitalization and after discharging to the home
      care. Circulatory arrest survivors are not provided routinely with psychological
      care. Patients included in our pilot research were identified in the register of
      surviving circulatory arrest. The survey was carried out using a non-standardized
      questionnaire. A total of 28 patients surviving the circulatory arrest were
      included in the pilot research. The average age of respondents was 54 years.
      There were 20 men and 8 women. The project showed that 18 (64.3 %) people, since
      they went through the critical status, have suffered from negative and bothering
      symptoms, such as: fear of a repeated cardiac arrest, sleeping disorders,
      persistent tiredness etc. Despite the fact that our group of patients was
      relatively small and larger studies addressing the issue are needed, our finding
      is alarming - the patients after the cardiac arrest suffer from many anxious and
      depressive symptoms as well as from cognitive deficit. In the situation when the
      common psychological intervention by a specialist is not provided, it seems that
      an early psychological invention is highly desirable and may have a beneficial
      effect on return of the patients to their everyday life.

PMID- 29336584
TI  - [Current macro-diagnostic trends of forensic medicine in the Czech Republic].
AB  - Over the last few years, advanced diagnostic methods have penetrated in the realm
      of forensic medicine in addition to standard autopsy techniques supported by
      traditional X-ray examination and macro-diagnostic laboratory tests. Despite the
      progress of imaging methods, the conventional autopsy has remained basic and
      essential diagnostic tool in forensic medicine. Postmortem computed tomography
      and magnetic resonance imaging are far the most progressive modern radio
      diagnostic methods setting the current trend of virtual autopsies all over the
      world. Up to now, only two institutes of forensic medicine have available
      postmortem computed tomography for routine diagnostic purposes in the Czech
      Republic. Postmortem magnetic resonance is currently unattainable for routine
      diagnostic use and was employed only for experimental purposes. Photogrammetry is
      digital method focused primarily on body surface imaging. Recently, the most
      fruitful results have been yielded from the interdisciplinary cooperation between
      forensic medicine and forensic anthropology with the implementation of body
      scanning techniques and 3D printing. Non-invasive and mini-invasive investigative
      methods such as postmortem sonography and postmortem endoscopy was
      unsystematically tested for diagnostic performance with good outcomes despite of
      limitations of these methods in postmortem application. Other futuristic methods,
      such as the use of a drone to inspect the crime scene are still experimental
      tools. The authors of the article present a basic overview of the both routinely
      and experimentally used investigative methods and current macro-diagnostic trends
      of the forensic medicine in the Czech Republic.

PMID- 29336585
TI  - [The Guideline on Spiritual Care of the Ministry of Health of the Czech
      Republic].
AB  - In April 2017, the Ministry of Health of the Czech Republic issued a Guideline on
      Spiritual Care in Bedside Medical Facilities of Medical Service Providers.
      Through this document, the ministry established the much-needed framework for the
      operation of hospital chaplains in medical facilities, including the conditions
      for their activities, and defined some terms such as spiritual care, chaplains,
      etc. Although this is an important initiative on the part of the ministry, the
      guideline does not cover a number of aspects of spiritual care in bedside medical
      facilities and will need some specification and completion.

PMID- 29336586
TI  - Image Information Obtained Using a Charge-Coupled Device (CCD) Camera During an
      Immersion Liquid Evaporation Process for Measuring the Refractive Index of Solid
      Particles.
AB  - The refractive index is a fundamental physical property of a medium, which can be
      used for the identification and purity issues of all media. Here we describe a
      refractive index measurement technique to determine simultaneously the refractive
      index of different solid particles by monitoring the transmittance of light from
      a suspension using a charge-coupled device (CCD) camera. An important feature of
      the measurement is the liquid evaporation process for the refractive index
      matching of the solid particle and the immersion liquid; this was realized by
      using a pair of volatile and non-volatile immersion liquids. In this study,
      refractive indices of calcium fluoride (CaF2) and barium fluoride (BaF2) were
      determined using the proposed method.

PMID- 29336587
TI  - Spatially Resolved Spectral Powder Analysis: Experiments and Modeling.
AB  - Understanding the behavior of light in granular media is necessary for
      determining the sample size, shape, and weight when probing using fiber optic
      setups. This is required for a correct estimate of the active pharmaceutical
      ingredient content in a pharmaceutical blend via near-infrared spectroscopy.
      Several strategies to describe the behavior of light in granular and turbid media
      exist. A common approach is the Monte-Carlo simulation of individual photons and
      their description using mean free path lengths for scattering and absorption. In
      this work, we chose a complementary method by approximating these parameters via
      real physical counterparts, i.e., the particle size, shape, and density and the
      resulting chord lengths. Additionally, the wavelength dependence of refractive
      indices is incorporated. The obtained results were compared with those obtained
      in an experimental setup that included the SAM-Spec Felin probe head by Indatech
      for detecting spatially resolved spectra of samples. Our method facilitates the
      interpretation of the acquired experimental results by contrasting the optical
      response, the physical particle attributes, and the simulation results.

PMID- 29336588
TI  - Uncertainty of Integrated Intensity Following Line Profile Fitting of Multiline
      Spectra.
AB  - A novel method of determining the total uncertainty in the integrated intensity
      of fitted emission lines in multipeaked emission spectra is presented. The
      proposed method does not require an assumption of the type of line profile to be
      specified. The absolute difference between a fit and measured spectrum defines
      the uncertainty of the integrated signal intensity and is subsequently decomposed
      to determine the uncertainty of each peak in multiline fits. Decomposition relies
      on tabulating a weighting factor, which describes how each peak contributes to
      the total integral uncertainty. Applications of this method to quantitative
      approaches in laser-induced breakdown spectroscopy analysis are described.

PMID- 29336589
TI  - Near-Infrared Spectroscopy Screening to Allow Detection of Pathogenic
      Mitochondrial DNA Variants in Individuals with Unexplained Abnormal Fatigue: A
      Preliminary Study.
AB  - Unexplained abnormal fatigue is characterized by chronic fatigue persisting for
      at least six months and not sufficiently explained by any recognized medical
      condition. In this pilot study, twelve individuals with abnormal fatigue
      remaining unexplained after thorough screening were investigated using a near
      infrared (NIR) spectroscopy handgrip test. Four of them were found to have an
      abnormal oxygen extraction pattern similar to participants with documented
      mitochondrial myopathy. In three of the four individuals, diverse mitochondrial
      abnormalities were documented by spectrophotometric, immunocytological,
      fluorescent, and morphological analyses performed in skeletal muscle and in
      cultured skin fibroblasts. Three of the four participants with decreased muscular
      oxygen extraction were each shown to harbor a different homoplasmic pathogenic
      mitochondrial DNA point mutation (m.961T > C, m.1555A > G, m.14484T > C). In the
      fourth participant, the presence of multiple large mitochondrial DNA deletions
      was suspected in muscle tissue. In contrast, none of the eight abnormally
      fatigued participants with normal NIR spectroscopy results harbored either a
      pathogenic mitochondrial DNA point mutation or large deletions ( P < 0.001). This
      pilot study shows that NIR spectroscopy may serve as a noninvasive screening tool
      to delineate a subgroup (of participants) with mitochondrial dysfunction among
      the large group of individuals with unexplained abnormal fatigue.

PMID- 29336590
TI  - Modern perspectives on the health benefits of kefir in next generation sequencing
      era: Improvement of the host gut microbiota.
AB  - Kefir is a natural complex fermented milk product containing more than 50 species
      of probiotic bacteria and yeast, and has been demonstrated to have multiple
      properties conferring health benefits, including antiobesity, anti-hepatic
      steatosis, antioxidative, antiallergenic, antitumor, anti-inflammatory,
      cholesterol-lowering, constipation-alleviating, and antimicrobial properties. To
      better understand the underlying mechanisms of these benefits, we here review
      research on the effect of kefir (and kefir microorganisms) consumption to
      modulate the host gut microbiota. Owing to its excellent gastrointestinal
      resistance and colonization ability and wide ranges of microbial interaction,
      kefir has shown significant and wide-spectrum modulatory effects on the host gut
      microbiota. In particular, as a bacteria- and yeast-containing food, kefir can
      modulate both the gut microbiota and mycobiota. Since the association of this
      modulation with health benefit has only been addressed in a small number of
      recent studies thus far, further studies are needed to determine the precise
      mechanisms of the beneficial effects of kefir in relation to the modulation of
      the gut microbiota and mycobiota. Gaining this insight will surely help to take
      full advantage of this unique probiotic food.

PMID- 29336591
TI  - Adherence to antiretroviral therapy, stigma and behavioral risk factors in HIV
      infected adolescents in Asia.
AB  - We studied behavioral risks among HIV-infected and uninfected adolescents using
      an audio computer-assisted self-interview. A prospective cohort study was
      initiated between 2013 and 2014 in Malaysia, Thailand, and Vietnam. HIV-infected
      adolescents were matched to uninfected adolescents (4:1) by sex and age group (12
      14 and 15-18 years). We enrolled 250 HIV-infected (48% male; median age 14.5
      years; 93% perinatally infected) and 59 uninfected (51% male; median age 14.1
      years) adolescents. At enrollment, HIV-infected adolescents were on
      antiretroviral therapy (ART) for a median (IQR) of 7.5 (4.7-10.2) years, and 14%
      had HIV-RNA >1000 copies/mL; 19% reported adherence <80%. Eighty-four (34%) HIV
      infected and 26 (44%) uninfected adolescents reported having ever smoked
      cigarettes or drunk alcohol (p = 0.13); 10% of HIV-infected and 17% of uninfected
      adolescents reported having initiated sexual activity; 6 of the HIV-infected
      adolescents had HIV-RNA >1000 copies/mL. Risk behaviors were common among
      adolescents, with few differences between those with and without HIV.

PMID- 29336592
TI  - Changes in Body Mass Index, Leptin, and Leptin Receptor Polymorphisms and Breast
      Cancer Risk.
AB  - Obesity is a strong risk factor for breast cancer. The polymorphisms of leptin
      (LEP) and leptin receptor (LEPR) may be associated with breast cancer by
      regulator of adipose tissue mass and tumor cell growth. A total of 794 cases and
      805 matched controls were sequentially enrolled. Time-of-flight mass spectrometry
      was used to determine the LEPrs7799039, LEPRrs1137100, and LEPRrs1137101
      genotypes for each participant. Associations between polymorphisms of these
      genes, change in body mass index (BMI), and breast cancer risk were assessed by
      unconditional multivariable logistic regression models. The unconditional
      logistic regression model showed that persistent overweight (BMI >=24 kg/m2) over
      the preceding 10 years was associated with increased breast cancer risk in
      premenopausal women (odds ratio [OR] = 1.67, 95% confidence interval [CI]: 1.19
      2.35). No associations between LEPrs7799039, LEPRrs1137100, or LEPRrs1137101
      polymorphisms alone and breast cancer risk were found. Persistent overweight over
      the preceding 10 years and carrying the LEPrs7799039 AA genotype together
      increased breast cancer risk in premenopausal women (ORadj = 2.00, 95% CI: 1.26
      3.16). Persistent overweight over the preceding 10 years and carrying the
      LEPRrs1137100 GG genotype increased breast cancer risk in premenopausal women
      (ORadj = 1.68, 95% CI: 1.06-2.68). In premenopausal women, persistent overweight
      (BMI >=24 kg/m2) over the preceding 10 years increases breast cancer risk.
      Persistent overweight along with LEPrs7799039 AA or LEPRrs1137100 GG genotypes
      synergistically increase risk of breast cancer among premenopausal women.

PMID- 29336593
TI  - Effect of vitamin A supplementation on iron status in humans: A systematic review
      and meta-analysis.
AB  - Anemia is a worldwide public health problem that can be related to many causes,
      including vitamin A deficiency. The aim of this study was to assess and estimate
      the effect of vitamin A supplementation (VAS) on iron status biomarkers and
      anemia in humans. Six databases, including Cochrane, EMBASE, LILACS, Pubmed,
      Scopus and Web of Science, were searched for clinical trials and cohort studies
      that investigated the effect of vitamin A supplementation alone on iron status
      and anemia, without time-restriction. The search yielded 23 eligible studies, 21
      clinical trials and 2 cohort studies, with children, teenagers, pregnant or
      lactating women. The meta-analysis of the clinical trials showed that VAS reduces
      the risk of anemia by 26% and raises hemoglobin levels, compared to non-treated
      group, independent of the life stage. VAS did not alter the prevalence of iron
      deficiency among the clinical trials conducted with children and teenagers (RR
      0.82, 95% CI 0.60 to 1.12, p = 0.204), whereas a significant increase in serum
      ferritin levels was observed in trials conducted with pregnant and lactating
      women (WMD 6.61 MUg/L; 95% CI 6.00 to 7.21 MUg/L; p < 0.001). Therefore, vitamin
      A supplementation alone may reduce the risk of anemia, by improving hemoglobin
      and ferritin levels in individuals with low serum retinol levels.

PMID- 29336595
TI  - Exploitation of microbial antagonists for the control of postharvest diseases of
      fruits: a review.
AB  - Fungal diseases result in significant losses of fruits and vegetables during
      handling, transportation and storage. At present, post-production fungal spoilage
      is predominantly controlled by using synthetic fungicides. Under the global
      climate change scenario and with the need for sustainable agriculture, biological
      control methods of fungal diseases, using antagonistic microorganisms, are
      emerging as ecofriendly alternatives to the use of fungicides. The potential of
      microbial antagonists, isolated from a diversity of natural habitats, for
      postharvest disease suppression has been investigated. Postharvest biocontrol
      systems involve tripartite interaction between microbial antagonists, the
      pathogen and the host, affected by environmental conditions. Several modes for
      fungistatic activities of microbial antagonists have been suggested, including
      competition for nutrients and space, mycoparasitism, secretion of antifungal
      antibiotics and volatile metabolites and induction of host resistance.
      Postharvest application of microbial antagonists is more successful for efficient
      disease control in comparison to pre-harvest application. Attempts have also been
      made to improve the overall efficacy of antagonists by combining them with
      different physical and chemical substances and methods. Globally, many microbe
      based biocontrol products have been developed and registered for commercial use.
      The present review provides a brief overview on the use of microbial antagonists
      as postharvest biocontrol agents and summarises information on their isolation,
      mechanisms of action, application methods, efficacy enhancement, product
      formulation and commercialisation.

PMID- 29336594
TI  - Incorporating Whole-Genome Sequencing into Public Health Surveillance: Lessons
      from Prospective Sequencing of Salmonella Typhimurium in Australia.
AB  - In Australia, the incidence of Salmonella Typhimurium has increased dramatically
      over the past decade. Whole-genome sequencing (WGS) is transforming public health
      microbiology, but poses challenges for surveillance. To compare WGS-based
      approaches with conventional typing for Salmonella surveillance, we performed
      concurrent WGS and multilocus variable-number tandem-repeat analysis (MLVA) of
      Salmonella Typhimurium isolates from the Australian Capital Territory (ACT) for a
      period of 5 months. We exchanged data via a central shared virtual machine and
      performed comparative genomic analyses. Epidemiological evidence was integrated
      with WGS-derived data to identify related isolates and sources of infection, and
      we compared WGS data for surveillance with findings from MLVA typing. We found
      that WGS data combined with epidemiological data linked an additional 9% of
      isolates to at least one other isolate in the study in contrast to MLVA and
      epidemiological data, and 19% more isolates than epidemiological data alone.
      Analysis of risk factors showed that in one WGS-defined cluster, human cases had
      higher odds of purchasing a single egg brand. While WGS was more sensitive and
      specific than conventional typing methods, we identified barriers to uptake of
      genomic surveillance around complexity of reporting of WGS results, timeliness,
      acceptability, and stability. In conclusion, WGS offers higher resolution of
      Salmonella Typhimurium laboratory surveillance than existing methods and can
      provide further evidence on sources of infection in case and outbreak
      investigations for public health action. However, there are several challenges
      that need to be addressed for effective implementation of genomic surveillance in
      Australia.

PMID- 29336596
TI  - HIV-related thought avoidance, sexual risk, and alcohol use among men who have
      sex with men.
AB  - HIV-related "cognitive escape" refers to a tendency to avoid thoughts associated
      with HIV, which may be particularly common among men who have sex with men (MSM)
      who are often inundated with HIV information, potentially to the point of
      fatigue. HIV-related cognitive escape is associated with increased sexual risk
      behaviors, such as condomless sex, and heavier alcohol use patterns. Other
      studies show that some MSM may use alcohol specifically to facilitate sex. These
      sexual motives for drinking (SMDs) could be one mechanism whereby cognitive
      escape leads to health risk behaviors. In this study, we tested models exploring
      whether cognitive escape was associated with markers of sex risk (condom use,
      number of sex partners) and alcohol use/problems, and examined whether SMDs
      mediated these associations. Heavy drinking, HIV-negative men (N = 196) aged >=
      21 years who self-reported past year condomless anal sex with men completed
      assessments as part of a larger study. Results suggest that cognitive escape was
      associated with higher number of anal sex partners (incidence rate ratio [IRR] =
      1.50, SE = 0.04, p < .001), decreased condom use (B = -0.30, SE = 0.14, p =
      .028), and increased alcohol-related problems (IRR = 1.28, SE = 0.07, p = .001)
      but not with drinking quantity. Sexual motives for drinking appeared to partially
      mediate the observed relationship between cognitive escape and alcohol-related
      problems, but other relationships did not show evidence of mediation. Findings
      suggest that those who tend to avoid HIV-related thoughts may be at increased
      risk for HIV and alcohol-related problems. Drinking to facilitate sex may
      partially account for the higher risk for alcohol-related problems conferred by
      cognitive escape. Alcohol interventions for MSM may be more effective if they
      address alcohol's role in coping with HIV threat and in facilitating sex under
      these circumstances.

PMID- 29336597
TI  - Navigating emotions and relationship dynamics: family life review as a clinical
      tool for older adults during a relocation transition into an assisted living
      facility.
AB  - OBJECTIVE: Relocation for the purpose of receiving care may be one of the more
      challenging transitions for older adults. The purpose of this study was to
      facilitate a family life review (FLR) session aimed at enhancing family
      relationships and assisting older adults in coping with the challenges associated
      with a relocation. METHODS: Fourteen dyads comprised of older adults who
      relocated to an assisted living facility (ALF) and a chosen family member or
      friend participated in a FLR session and semi-structured follow up interview.
      Data were analyzed using the constant comparative method and triangulated with
      descriptive statistics. RESULTS: Emergent themes suggested participating in FLR
      influenced families by raising emotions, systemically thinking, and navigating
      the relocation. FLR facilitated positive connections, enhanced existing
      relationships, and promoted self-acceptance. Families indicated mutual
      storytelling was enjoyable and reminded them of the urgency to share their story.
      FLR allowed dyads to reflect and thus prompted a renewed perspective on some of
      the more challenging components of the relocation transition. CONCLUSION: Study
      findings provide insight into how families organize individual and interpersonal
      narratives and use these narratives during transitional times. FLR can aid
      families in making a smoother and fulfilling move to an ALF and other late life
      transitions.

PMID- 29336598
TI  - Quantitative MR Evaluation of Chronic Pancreatitis: Extracellular Volume Fraction
      and MR Relaxometry.
AB  - OBJECTIVE: The purpose of this study was to determine if extracellular volume
      fraction and T1 mapping can be used to diagnose chronic pancreatitis (CP).
      MATERIALS AND METHODS: This HIPAA-compliant study analyzed 143 consecutive
      patients with and without CP who underwent MR imaging between May 2016 and
      February 2017. Patients were selected for the study according to inclusion and
      exclusion criteria that considered history and clinical and laboratory findings.
      Eligible patients (n = 119) were grouped as normal (n = 60) or with mild (n =
      22), moderate (n = 27), or severe (n = 10) CP on the basis of MRCP findings using
      the Cambridge classification as the reference standard. T1 maps were acquired in
      unenhanced and late contrast-enhanced phases using a 3D dual flip-angle gradient
      echo sequence. All patients were imaged on the same 3-T scanner using the same
      imaging parameters, contrast agent, and dosage. RESULTS: Mean extracellular
      volume fractions and T1 relaxation times were significantly different within the
      study groups (one-way ANOVA, p < 0.001). Using the AUC curve analysis,
      extracellular volume fraction of > 0.27 showed 92% sensitivity (54/59) and 77%
      specificity (46/60) for the diagnosis of CP (AUC = 0.90). A T1 relaxation time of
      > 950 ms revealed 64% sensitivity (38/59) and 88% specificity (53/60) (AUC =
      0.80). Combining extracellular volume fraction and T1 mapping yielded sensitivity
      of 85% (50/59) and specificity of 92% (55/60) (AUC = 0.94). CONCLUSION:
      Extracellular volume fraction and T1 mapping may provide quantitative metrics for
      determining the presence and severity of acinar cell loss and aid in the
      diagnosis of CP.

PMID- 29336599
TI  - Femoral Neck Stress Injuries: Analysis of 156 Cases in a U.S. Military Population
      and Proposal of a New MRI Classification System.
AB  - OBJECTIVE: The objective of this study is to formulate a new MRI classification
      system for fatigue-type femoral neck stress injuries (FNSIs) that is based on
      patient management and return-to-duty (RTD) time. MATERIALS AND METHODS: A
      retrospective review of 156 consecutive FNSIs in 127 U.S. Army soldiers over a 24
      month period was performed. The width of marrow edema for low-grade FNSIs and the
      measurement of macroscopic fracture as a percentage of femoral neck width for
      high-grade FNSIs were recorded. RTD time was available for 90 soldiers.
      Nonparametric testing, univariate linear regression, and survival analysis on RTD
      time were used in conjunction with patient management criteria to develop a new
      FNSI MRI classification system. RESULTS: The FNSI incidence was 0.09%, and all
      FNSIs were compressive-sided injuries. RTD time was significantly longer for high
      grade FNSIs versus low-grade FNSIs (p < 0.001). Our FNSI MRI classification
      system showed a significant difference in RTD time between grades 1 and 2 (p =
      0.001-0.029), 1 and 3 (p < 0.001), and 1 and 4 (p = 0.001-0.01). There was no
      significant RTD time difference between the remaining grades. The rates of
      completing basic training (BT) and requiring medical discharge were significantly
      associated with the FNSI MRI grades (p = 0.038 and p = 0.001, respectively).
      CONCLUSION: The proposed FNSI MRI classification system provides a robust
      framework for patient management optimization by permitting differentiation
      between operative and nonoperative candidates, by allowing accurate prediction of
      RTD time, and by estimating the risk of not completing BT and requiring medical
      discharge from the military.

PMID- 29336600
TI  - Current Clinical Practice Patterns of Self-Identified Interventional
      Radiologists.
AB  - OBJECTIVE: The purpose of this study was to assess patterns of procedural,
      clinical evaluation and management (E/M), and diagnostic imaging services
      rendered by self-identified interventional radiologists (IRs) across the United
      States. MATERIALS AND METHODS: Recent Medicare Physician and Other Supplier
      Public Use and Physician Compare national downloadable files were linked. IRs
      were defined as physicians self-identifying interventional radiology as their
      primary specialty on Medicare claims or as a specialty during Medicare
      enrollment. The primary outcome measure was percentage of work (in work relative
      value units [WRVU]) attributed to interventional services (both procedural and
      E/M) per IR. Secondary outcome measures included sociodemographic factors per
      interventional WRVU quartile and percentage of E/M service units per IR.
      Statistical analysis included chi-square and t tests and logistic regression.
      RESULTS: Overall, 3132 physicians nationally self-identified to Medicare as IRs.
      The distribution of WRVU attributed to interventional services was strongly
      bimodal. Procedures and E/M together accounted for >= 91% and <= 5% of total work
      for the most and least intervention-oriented quartiles, respectively, but were
      widely distributed in the middle two quartiles. The most intervention-oriented
      self-identified IRs were more likely out of medical school <= 30 years (odds
      ratio [OR], 2.5; p < 0.0001), men (OR, 2.2; p < 0.0001), and in academic practice
      (OR, 4.3; p < 0.0001). E/M accounted for only 1.4% of all billed services.
      CONCLUSION: Although most self-identified IRs perform both interventional and
      diagnostic imaging services, the subspecialty distribution is strongly bimodal,
      one-quarter each focusing <= 5% and >= 91% of work on interventional services.
      Despite ongoing emphasis on clinically focused interventional radiology, E/M
      services remain rarely reported.

PMID- 29336601
TI  - JOURNAL CLUB: Computer-Aided Detection of Lung Nodules on CT With a Computerized
      Pulmonary Vessel Suppressed Function.
AB  - OBJECTIVE: The purpose of this study is to evaluate radiologists' performance in
      detecting actionable nodules on chest CT when aided by a pulmonary vessel image
      suppressed function and a computer-aided detection (CADe) system. MATERIALS AND
      METHODS: A novel computerized pulmonary vessel image-suppressed function with a
      built-in CADe (VIS/CADe) system was developed to assist radiologists in
      interpreting thoracic CT images. Twelve radiologists participated in a
      comparative study without and with the VIS/CADe using 324 cases (involving 95
      cancers and 83 benign nodules). The ratio of nodule-free cases to cases with
      nodules was 2:1 in the study. Localization ROC (LROC) methods were used for
      analysis. RESULTS: In a stand-alone test, the VIS/CADe system detected 89.5% and
      82.0% of malignant nodules and all nodules no smaller than 5 mm, respectively.
      The false-positive rate per CT study was 0.58. For the reader study, the mean
      area under the LROC curve (LROCAUC) for the detection of lung cancer
      significantly increased from 0.633 when unaided by VIS/CADe to 0.773 when aided
      by VIS/CADe (p < 0.01). For the detection of all clinically actionable nodules,
      the mean LROC-AUC significantly increased from 0.584 when unaided by VIS/CADe to
      0.692 when detection was aided by VIS/CADe (p < 0.01). Radiologists detected
      80.0% of cancers with VIS/CADe versus 64.45% of cancers unaided (p < 0.01);
      specificity decreased from 89.9% to 84.4% (p < 0.01). Radiologist interpretation
      time significantly decreased by 26%. CONCLUSION: The VIS/CADe system
      significantly increased radiologists' detection of cancers and actionable nodules
      with somewhat lower specificity. With use of the VIS/CADe system, radiologists
      increased their interpretation speed by a factor of approximately one-fourth. Our
      study suggests that the technique has the potential to assist radiologists in the
      detection of additional actionable nodules on thoracic CT.

PMID- 29336602
TI  - Surface Spectroscopic Signatures of Mechanical Deformation in High-Density
      Polyethylene (HDPE).
AB  - High-density polyethylene (HDPE) has been extensively studied, both as a model
      for semi-crystalline polymers and because of its own industrial utility. During
      cold drawing, crystalline regions of HDPE are known to break up and align with
      the direction of tensile load. Structural changes due to deformation should also
      manifest at the surface of the polymer, but until now, a detailed molecular
      understanding of how the surface responds to mechanical deformation has been
      lacking. This work establishes a precedent for using vibrational sum-frequency
      generation (VSFG) spectroscopy to investigate changes in the molecular-level
      structure of the surface of HDPE after cold drawing. X-ray diffraction (XRD) was
      used to confirm that the observed surface behavior corresponds to the expected
      bulk response. Before tensile loading, the VSFG spectra indicate that there is
      significant variability in the surface structure and tilt of the methylene groups
      away from the surface normal. After deformation, the VSFG spectroscopic
      signatures are notably different. These changes suggest that hydrocarbon chains
      at the surface of visibly necked HDPE are aligned with the direction of loading,
      while the associated methylene groups are oriented with the local C2v symmetry
      axis roughly parallel to the surface normal. Small amounts of unaltered material
      are also found at the surface of necked HDPE, with the relative amount of
      unaltered material decreasing as the amount of deformation increases. Aspects of
      the nonresonant SFG response in the transition zone between necked and undeformed
      polymer provide additional insight into the deformation process and may provide
      the first indication of mechanical deformation. Nonlinear surface spectroscopy
      can thus be used as a noninvasive and nondestructive tool to probe the stress
      history of a HPDE sample in situations where X-ray techniques are not available
      or not applicable. Vibrational sum-frequency generation thus has great potential
      as a platform for material state awareness (MSA) and should be considered as part
      of a broader suite of tools for such applications.

PMID- 29336603
TI  - Comparison of Unlicensed and Off-Label Use of Antipsychotics Prescribed to Child
      and Adolescent Psychiatric Outpatients for Treatment of Mental and Behavioral
      Disorders with Different Guidelines: The China Food and Drug Administration
      Versus the FDA.
AB  - OBJECTIVES: This study aims to compare the prevalence of unlicensed and off-label
      use of antipsychotics among child and adolescent psychiatric outpatients with
      guidelines proposed by the China Food and Drug Administration (CFDA) and the U.S.
      Food and Drug Administration (FDA), and to identify factors associated with
      inconsistencies between the two regulations. METHODS: A retrospective analysis of
      29,326 drug prescriptions for child and adolescent outpatients from the
      Affiliated Brain Hospital of Guangzhou Medical University was conducted.
      Antipsychotics were classified as "unlicensed" or "off-label use" according to
      the latest pediatric license information registered by the CFDA and the FDA or
      the package inserts of antipsychotics authorized by the CFDA or the FDA for the
      treatment of pediatric mental and behavioral disorders, respectively. Binary
      logistic regression analysis was performed to assess factors associated with
      inconsistencies between the two regulations. RESULTS: The total unlicensed use,
      according to the CFDA analysis, was higher than that found in the FDA analysis
      (74.14% vs. 22.04%, p < 0.001). However, the total off-label use, according to
      the FDA analysis, was higher than that found in the CFDA analysis (46.53% vs.
      15.77%, p < 0.001). Antipsychotic drug classes, age group, number of diagnoses,
      and diagnosis of schizophrenia and schizotypal and delusional disorders were
      associated with inconsistent unlicensed use. Antipsychotic drug classes, age
      group, number of prescribed psychotropic drugs, gender, diagnosis of
      schizophrenia and schizotypal and delusional disorders, diagnosis of mood
      [affective] disorders, diagnosis of mental retardation, and diagnosis of
      psychological development disorders were associated with inconsistent off-label
      use. CONCLUSIONS: The difference in prevalence of total unlicensed and off-label
      use of antipsychotics between the two regulations was statistically significant.
      This inconsistency could be partly attributed to differences in pediatric license
      information and package inserts of antipsychotics. The results indicate a need
      for further clinical pediatric studies and better harmonization between agencies
      regarding antipsychotic used in pediatrics.

PMID- 29336604
TI  - Family Functioning and Mental Health of Transgender and Gender-Nonconforming
      Youth in the Trans Teen and Family Narratives Project.
AB  - Transgender and gender-nonconforming (TGN) youth are at increased risk for
      adverse mental health outcomes, but better family functioning may be protective.
      This study describes TGN youth's mental health and associations with family
      functioning in a community-based sample. Participants were from 33 families (96
      family members) and included 33 TGN youth, ages 13 to 17 years; 48 cisgender (non
      transgender) caregivers; and 15 cisgender siblings. Participants completed a
      survey with measures of family functioning (family communication, family
      satisfaction) and mental health of TGN youth (suicidality, self-harm, depression,
      anxiety, self-esteem, resilience). TGN youth reported a high risk of mental
      health concerns: suicidality (15% to 30%), self-harm (49%), clinically
      significant depressive symptoms (61%); and moderate self-esteem (M = 27.55, SD =
      7.15) and resiliency (M = 3.67, SD = 0.53). In adjusted models, better family
      functioning from the TGN youth's perspective was associated with better mental
      health outcomes among TGN youth (beta ranged from -0.40 to -0.65 for self-harm,
      depressive symptoms, and anxious symptoms, and 0.58 to 0.70 for self-esteem and
      resiliency). Findings from this study highlight the importance of considering TGN
      youth's perspectives on the family to inform interventions to improve family
      functioning in families with TGN youth.

PMID- 29336606
TI  - Update on Molecular Testing for Cytologically Indeterminate Thyroid Nodules.
AB  - CONTEXT: - Approximately 15% to 30% of thyroid nodules that undergo fine-needle
      aspiration are classified as cytologically indeterminate, presenting management
      challenges for patients and clinicians alike. During the past several years,
      several molecular tests have been developed to reduce the diagnostic uncertainty
      of indeterminate thyroid fine-needle aspirations. OBJECTIVE: - To review the
      methodology, clinical validation, and recent peer-reviewed literature for 4
      molecular tests that are currently marketed for cytologically indeterminate
      thyroid fine-needle aspiration specimens: Afirma, ThyroSeq, ThyGenX/ThyraMIR, and
      RosettaGX Reveal. DATA SOURCES: - Peer-reviewed literature retrieved from PubMed
      search, data provided by company websites and representatives, and authors'
      personal experiences. CONCLUSIONS: - The 4 commercially available molecular tests
      for thyroid cytology offer unique approaches to improve the risk stratification
      of thyroid nodules. Familiarity with data from the validation studies as well as
      the emerging literature about test performance in the postvalidation setting can
      help users to select and interpret these tests in a clinically meaningful way.

PMID- 29336605
TI  - Colorectal Carcinomas With Isolated Loss of PMS2 Staining by
      Immunohistochemistry.
AB  - CONTEXT: - Isolated loss of PMS2 staining is an uncommon immunophenotype in
      colorectal carcinomas, accounting for approximately 4% of tumors with
      microsatellite instability. Limited information regarding these tumors is
      available in the literature. OBJECTIVE: - To compare the clinicopathologic
      features of colorectal carcinomas with isolated PMS2 loss by immunohistochemistry
      to those with other forms of mismatch repair deficiency. DESIGN: - Ninety-three
      colorectal carcinomas with isolated PMS2 loss by immunohistochemistry and 193
      with other forms of mismatch repair deficiency were identified. Forty (43%) of
      the isolated PMS2 loss cases and 35 control cases (18%) had a known germline
      mutation or a clinical diagnosis of Lynch syndrome. RESULTS: - Overall, isolated
      PMS2-loss tumors occurred in significantly younger patients ( P < .001) and in
      fewer female patients ( P = .006). These tumors were significantly less likely to
      be right-sided ( P = .001), high-grade ( P = .01), or display histologic features
      of microsatellite instability ( P < .001). The isolated PMS2-loss group also
      exhibited increased odds of disease-specific death (odds ratio [OR], 3.09; 95%
      CI, 1.41-6.85; P = .007). When the analysis was restricted to germline
      mutation/Lynch syndrome cases and controls, no significant differences were
      detected for age, sex, tumor location, tumor grade, histologic features, or
      distant metastases, although a trend toward increased odds of disease-specific
      death in the isolated PMS2-loss group was evident (OR, 3.87; 95% CI, 0.89-27.04;
      P = .10). CONCLUSIONS: - Unusual clinicopathologic features observed in
      colorectal carcinomas with isolated PMS2 loss are likely related to the high
      proportion of cases caused by germline mutations. Isolated PMS2-loss tumors may
      demonstrate more aggressive behavior than other tumors with microsatellite
      instability, but larger studies are needed to investigate that possibility
      further.

PMID- 29336607
TI  - Alu siRNA to increase Alu element methylation and prevent DNA damage.
AB  - : Global DNA hypomethylation promoting genomic instability leads to cancer and
      deterioration of human health with age. AIM: To invent a biotechnology that can
      reprogram this process. METHODS: We used Alu siRNA to direct Alu interspersed
      repetitive sequences methylation in human cells. We evaluated the correlation
      between DNA damage and Alu methylation levels. RESULTS: We observed an inverse
      correlation between Alu element methylation and endogenous DNA damage in white
      blood cells. Cells transfected with Alu siRNA exhibited high Alu methylation
      levels, increased proliferation, reduced endogenous DNA damage and improved
      resistance to DNA damaging agents. CONCLUSION: Alu methylation stabilizes the
      genome by preventing accumulation of DNA damage. Alu siRNA could be useful for
      evaluating reprograming of the global hypomethylation phenotype in cancer and
      aging cells.

PMID- 29336608
TI  - Prevalence of frailty and its association with depressive symptoms among older
      adults in Singapore.
AB  - OBJECTIVES: The aims of the study were to (1) estimate the prevalence of frailty
      among community-dwelling older adults , and (2) investigate the independent
      association between level of frailty and depressive symptoms. METHODS: A total of
      721 older adults (aged 60 and above ) were included in this study. Severity of
      frailty was determined using the Clinical Frailty Scale and further classified
      into four levels (CFS1-3: F1, CFS4: F2, CFS5: F3, and CFS6-7: F4). The depressive
      symptoms were assessed using the Patient Health Questionnaire-9. The prevalence
      of frailty by four levels was described and the association between level of
      frailty and depressive symptoms was assessed using multiple linear regression.
      RESULTS: The prevalence of frailty among the study population was 24.5% (F2:
      14.4%, F3:3.7%, F4: 6.4%). There was no significant difference in level of
      frailty between male and female. With the increase in severity level of frailty,
      older adults reported substantially higher depressive symptom scores (p < .001),
      even after controlling for socio-demographics, number of non-mental chronic
      conditions, and number of medications taken regularly. CONCLUSIONS: Level of
      frailty is independently associated with depressive symptoms among community
      dwelling older population, which is not fully explained by symptom overlap, socio
      demographic, and comorbidity covariates.

PMID- 29336609
TI  - Fibroblast growth factor 23 (FGF23) gene polymorphisms are associated with
      essential hypertension risk and blood pressure levels in Chinese Han population.
AB  - In this case-control study, 246 EH patients and 157 healthy controls were
      selected from Chinese Han population to explore the associations between the
      fibroblast growth factor 23 (FGF23) gene polymorphisms and essential hypertension
      (EH).The SequenomMassarray system was used for the genotyping of three FGF23 gene
      Tag single-nucleotide polymorphisms, namely rs7955866, rs13312756, and rs3812822.
      The primers were designed by Assay Designer 3.1 software, and then the samples
      were added to a 384-well plate for the polymerase chain reaction amplification,
      shrimp alkaline phosphatase reaction, and desalting after extension. The
      distributions of the alleles, genotypes, and haplotypes were compared between the
      two groups. Confounding factors (sex, age, BMI, smoking, and drinking) were
      adjusted in the non-logistic regression, and the results showed that rs7955866
      and rs3812822 polymorphisms were independently associated with the risk of
      developing EH (P < 0.05). The statistical analysis of the haplotype of rs7955866
      rs13312756-rs3812822 showed that haplotype ACC could increase the risk of
      developing EH (P = 0.046; OR = 1.513, 95%CI: 1.005-2.278). The analysis of the
      control group showed that carrying rs7955866 A allele (P = 0.031) and rs3812822 C
      allele (P = 0.025) was associated with the increase of systolic blood pressure
      (SBP). The insulin (INS) level in the peripheral blood was significantly
      different between the case and control groups (P = 0.014). After confounding
      factors were excluded, the results showed that the serum INS level was also an
      independent risk factor of developing EH (P = 0.044; OR = 1.604, 95%CI: 1.014
      2.539). In summary, our results suggest that FGF23 gene polymorphisms are
      associated with the risk of developing EH in Chinese Han population.

PMID- 29336610
TI  - NrF2/ARE and NF-kappaB pathway regulation may be the mechanism for lutein
      inhibition of human breast cancer cell.
AB  - AIM: Though lutein can inhibit cancer cell proliferation via alleviating
      oxidative injury, the molecular mechanisms of lutein involvement in the
      NrF2/antioxidant response element (ARE) and NF-kappaB pathways remain poorly
      understood. MATERIALS & METHODS: MTT, flow cytometry, quantitative real-time PCR
      (qRT-PCR) and western blot assays were performed. RESULTS: After treatment with
      lutein, breast cancer cell proliferation was significantly decreased in a dose
      dependent manner. Lutein induced nuclear translocation and protein expression of
      NrF2, improved the expression of cellular antioxidant enzymes and attenuated
      reactive oxygen species levels. Moreover, lutein treatment decreased NF-kappaB
      signaling pathway related NF-kappaB p65 protein expression. CONCLUSION: The
      effect of lutein antiproliferation was mediated by activation of the NrF2/ARE
      pathway, and blocking of the NF-kappaB signaling pathway.

PMID- 29336611
TI  - Interventions to improve benzodiazepine tapering success in the elderly: a
      systematic review.
AB  - BACKGROUND: Long-term benzodiazepine use in the elderly population is a
      significant public health problem that leads to impaired cognitive functioning,
      medication dependence and increased risks for adverse drug reactions. The aim of
      this review was to examine randomized controlled trials (RCTs) on the efficacy of
      different methods for tapering and discontinuing benzodiazepines. METHOD: We used
      four databases (Ovid, PubMed, Academic Search Complete, Web of Science) to
      retrieve randomized controlled trials published in peer-reviewed journals that
      explored different methods for tapering benzodiazepine use in a primarily
      geriatric population. RESULTS: Eleven papers met the inclusion criteria. Methods
      to assist in benzodiazepine tapering included patient education, cognitive
      behavioural therapy (CBT), and pharmaceutical adjuvants (SSRIs, melatonin,
      progesterone). Patient education was consistently effective in increasing
      benzodiazepine discontinuation success while CBT had mixed but promising results.
      The use of medications to help improve tapering success was inconclusive.
      CONCLUSIONS: Patient education is a successful, time- and cost-effective
      intervention that can significantly help with benzodiazepine discontinuation
      success. CBT may also be an effective approach. However, cost can be an issue
      since public healthcare coverage in Canada does not cover psychotherapy. More
      research is needed in looking at pharmaceutical adjuvants and their role in
      assisting with benzodiazepine discontinuation.

PMID- 29336613
TI  - Breastfeeding: The Road Less Traveled.

PMID- 29336612
TI  - Relationship among adiponectin, insulin resistance and atherosclerosis in non
      diabetic hypertensive patients and healthy adults.
AB  - Adiponectin, which is secreted specifically by adipose tissue, has been shown to
      have anti-atherogenic and anti-inflammatory effects and to improve insulin
      resistance (IR). The aim of this study was to determine the correlations among
      adiponectin, IR and atherosclerosis in non-diabetic hypertensive patients and
      healthy volunteers. In this case control study, we collected complete demographic
      data from and measured several laboratory parameters in all enrolled subjects.
      The homeostasis model of assessment for insulin resistance (HOMA-IR) was
      calculated as an insulin sensitivity index. The atherogenic index of plasma
      (AIP), which is calculated as log (triglyceride (TG)/high-density lipoprotein
      cholesterol (HDL-C)), was a significant predictor of atherosclerosis and was a
      better predictor of atherosclerosis than low-density lipoprotein cholesterol (LDL
      C). Plasma adiponectin, interleukin (IL)-6, monocyte chemoattractant protein-1
      (MCP-1) and matrix metalloprotein-9 (MMP-9) concentrations were determined using
      enzyme-linked immunosorbent assay (ELISA). All data were analyzed using
      Statistical Product and Service Solutions for Windows (SPSS) 13.0 software. A
      total of 309 participants were enrolled in the study. Hypertensive patients with
      IR (n = 93) displayed significantly higher HOMA-IR values and AIPs and lower
      adiponectin levels than hypertensive patients without IR (n = 121) and healthy
      adults (n = 95) (P < 0.05). Furthermore, circulating IL-6, MCP-1 and MMP-9
      concentrations differed significantly between hypertensive patients and healthy
      adults (P < 0.05). Additionally, adiponectin levels were found to be inversely
      correlated with IL-6, MCP-1, and MMP-9 levels; HOMA-IR values; and AIPs in the
      clinical study. HOMA-IR values and adiponectin and creatinine (Cr) concentrations
      remained independently associated with AIPs in all participants after adjustment
      for confounders via multivariate linear regression. Low adiponectin levels are
      positively correlated with decreased insulin sensitivity, increased pro
      inflammatory cytokine production and worsening atherosclerosis in hypertensive
      patients and healthy adults.

PMID- 29336614
TI  - Evaluation of Corneal Parameters with Dual Scheimpflug Imaging in Patients with
      Systemic Sclerosis.
AB  - PURPOSE: To evaluate the cornea of systemic sclerosis (SSc) patients with Dual
      Scheimpflug Imaging. METHODS: Twenty consecutive SSc patients and 20 age and sex
      matched controls were enrolled in this cross-sectional study. Corneal
      measurements were acquired by dual Scheimpflug analyzer. RESULTS: SSc patients
      had statistically significant steeper corneas than the control group. The mean
      anterior curvature-average (SimK) was 44.93 +/- 1.64 D (mean +/- standard
      deviation) in SSc and 43.61 +/- 0.99D in control group, p = 0.01. Posterior
      curvature was also steeper in SSc patients compared to controls (p = 0.02). There
      was no statistically significant difference regarding central average pachymetry
      (p = 0.07), thinnest pachymetry (p = 0.09). CONCLUSIONS: Patients with SSc
      present with steeper corneas than controls.

PMID- 29336615
TI  - Pharmacokinetic bioequivalence, safety and acceptability of Ornibel(r), a new
      polymer composition contraceptive vaginal ring (etonogestrel/ethinylestradiol
      11.00/3.474 mg) compared with Nuvaring(r) (etonogestrel/ethinylestradiol 11.7/2.7
      mg).
AB  - OBJECTIVE: To show the clinical development of Ornibel(r) (ExeltisHealthcare,
      Spain) a contraceptive vaginal ring manufactured with a new polymer composition
      and containing etonogestrel/ethinylestradiol, compared to Nuvaring(r) (MSD,
      Spain). SUBJECTS AND METHODS: Randomised, single dose, 2-period, 2-sequence, 2
      stage crossover, comparative bioavailability study conducted in 40 healthy female
      subjects. All subjects received both treatments for 28 days in each of two
      periods, separated by a 28 days washout. Ornibel(r) contains
      etonogestrel/ethinylestradiol 11.00/3.47 mg and Nuvaring(r) contains
      etonogestrel/ethinylestradiol 11.7/2.7 mg, both rings delivering 120/15 ug/day.
      For the calculation of pharmacokinetic parameters, 37 blood samples were
      collected up to 840 h after each ring insertion to quantify plasma concentrations
      of etonogestrel and ethinylestradiol using a validated MS/MS-HPLC. Safety was
      assessed by adverse events recording, clinical laboratory and vital signs and
      tolerability by vaginal examination. Acceptability was investigated by a 5-point
      scale questionnaire. RESULTS: Bioequivalence was demonstrated in the first stage
      as the 94.12% Confidence Intervals of the primary parameters laid within the 80
      125% acceptance range for both etonogestrel (Cmax: 96.81-112.20%; AUC0-504h:
      98.71-108.61%; AUC0-t: 100.14-109.10%) and ethinylestradiol. (Cmax: 105.91
      120.62%; AUC0-504h: 105.47-114.59%; AUC0-t: 108.31-117.61%). During the first day
      of use a burst effect was observed with Nuvaring(r), with significantly higher
      level of ethinylestradiol (Cmax0-24h ratio: 78.34%, 94.12CI: 73.55-83.45%). Both
      products were well tolerated and accepted, without significant differences
      between them. CONCLUSION: Ornibel(r) is bioequivalent to Nuvaring(r) in terms of
      efficacy, safety, tolerability and acceptability. The new polymer composition
      provides Ornibel(r) with more stability and gradual hormonal release during the
      first day of use, particularly for ethinylestradiol.

PMID- 29336616
TI  - Study of the osteoprotegerin/receptor activator of nuclear factor-kB ligand
      system association with inflammation and atherosclerosis in systemic sclerosis.
AB  - OBJECTIVE: we aimed to study systemic sclerosis patients in order to assess
      osteoprotegerin/Receptor activator of nuclear factor-kB ligand (OPG/RANKL) system
      and find the relation of these biomarkers with the clinical features of the
      disease, the carotid intima thickness, markers of inflammation, lipid profile,
      and other laboratory characteristics. METHODS: both the level of (RANKL), (OPG)
      in sera of participants, in 30 (SSc) patients and the atherosclerotic changes
      affecting the common carotid artery were measured and, were compared to 30
      healthy controls matched for age and sex. All participants were assessed
      clinically and subjected to the Revised Medsger SSc severity scale and underwent
      carotid Doppler ultrasound examination. RESULTS: OPG, RANKL, and RANKL/OPG were
      1.9 +/- 0.4 ng/ml, 24.3 +/- 17.25 ng/ml, and 13.5 +/-9.8 versus 0.77 +/- 0.25
      ng/ml, 7.13 +/- 3.02 ng/ml, and 9.6 +/- 3.1 in the SSc patients and the controls
      with significance (P = 0.001, P = 0.001, P = 0.045) respectively. The OPG- RANKL
      axis in the SSc patients correlated significantly with carotid intima thickness,
      arthritis, arthralgia, inflammatory markers, Medsger joint, Medsger vascular,
      Medsger skin, and dyslipidemia. CONCLUSION: In cardiovascular risks, OPG serum
      level might increase as a preventive compensatory mechanism to neutralize the
      RANKL level increment. The determination of the OPG-RANKL system is a diagnostic
      indicator for the intensity of vascular calcification and atherosclerosis in SSc
      patients.

PMID- 29336617
TI  - Incidental neuroblastoma with bilateral retinoblastoma: what are the chances?
AB  - A child with bilateral familial retinoblastoma underwent staging MRI brain and
      orbit which identified subtle leptomeningeal enhancement, thus prompting an MRI
      whole body, which revealed a retroperitoneal mass, confirmed on laparoscopic
      biopsy to be neuroblastoma. This is the first reported case of these two rare
      embryonal non-central nervous system tumors occurring concurrently. The cause of
      this concurrence is unknown despite their pathogenic similarities with a chance
      of 4 cases per 10 billion children aged 1-4 years. Incidental neuroblastomas in
      infants can regress spontaneously but this child underwent systemic chemotherapy
      for his retinoblastoma that may have caused regression of the neuroblastoma.

PMID- 29336619
TI  - Minimally Invasive Nerve-Sparing Radical Hysterectomy: A Win-Win Scenario.

PMID- 29336618
TI  - Rheumatoid arthritis: A single-center Egyptian experience.
AB  - OBJECTIVE: Demonstration of rheumatoid arthritis (RA) characteristics in a large
      cohort of Egyptian patients. METHODS: Retrospective analysis of data of 3219 RA
      patients attending the Rheumatology outpatient clinic, Kasr Alainy Hospital,
      Cairo University; from January 1995 till December 2015. RESULTS: Mean age at
      disease onset was 36.1 +/-13.4 years; 2774 (84%) were females and mean disease
      duration was 12.9 +/-7.9 years. Regarding number of joint affected at disease
      onset; polyarticular pattern was found in 77.1%, pattern of joint involvement;
      combined small and large joints involvement was in 83.2%, subcutaneous nodules in
      14.2%, interstitial lung disease in 0.3%, secondary Sjogren's syndrome in 10.5%,
      hand bony erosions at diagnosis in 20.6%. Rheumatoid factor was positive in 52%.
      There was annual increase in the newly diagnosed cases (P = 0.017) reflecting
      increase in patients' awareness and improvement of medical service, also annual
      increase in: mean age of onset (P < 0.001) reflecting changes in health measures,
      also in cases with monoarticular or oligoarticular patterns at disease onset (P =
      0.02, 0.01 respectively) reflecting earlier diagnosis of patients and in patients
      with small joint involvement (P = 0.001) with a significant decline in:
      polyarticular pattern (P = 0.001), combined small and large joint affection (P <
      0.001), and number of cases with hand bony erosions (P = 0.01) denoting earlier
      diagnosis, tight disease control. CONCLUSION: We found a female predominance,
      younger age at disease onset, lower frequency of extra articular manifestations,
      more frequent polyarticular pattern at disease onset and less erosive disease,
      denoting changing referral patterns, earlier diagnosis, improved disease control
      in Egyptian RA patients over 2 decades. ABBREVIATIONS: SNs: Subcutaneous nodules;
      2ry SS: 2ry Sjogren's syndrome; ILD: Interstitial lung disease; ACPA: Anti-cyclic
      citrullinated peptide antibodies; DMARDs: Disease modifying anti-rheumatic drugs.

PMID- 29336620
TI  - The role of the PI3K/mTOR signaling pathway in Staphylococcus epidermidis small
      colony variants intracellular survival.
AB  - The objective of this study was to analyze how Staphylococcus epidermidis SCV and
      WT strains manipulate the PI3K/Akt/mTOR signaling pathway. Six S. epidermidis
      strains with normal phenotype (WT) and six S. epidermidis strains with SCV
      phenotype were isolated in parallel from six patients with the prosthetic hip
      joint infections. THP-1 activated cells were incubated with or without PI3K
      inhibitor-wortmannin or with mTOR inhibitor-rapamycin. Next, macrophages were
      exposed to S. epidermidis WT and SCV strains. After 4 h incubation, bacterial
      survival inside macrophages as well as PI3K-mTOR activation was analyzed. SCV
      strains of S. epidermidis increased the level of Akt phosphorylation, compared to
      uninfected macrophages and to their parental WT forms. Wild type variants of S.
      epidermidis phosphorylated Akt at similar or lower levels as control uninfected
      cells. Next, the induction of mTOR target, phosphorylated ribosomal protein S6,
      was measured in bacteria-infected macrophages. The level of phosphorylation was
      significantly reduced when the cells were exposed to WT strains of S.
      epidermidis. In contrast, the SCV strains activated S6 protein mostly at a level
      comparable to the control cells. Rapamycin inhibited mTOR activation as the
      number of p-S6 positive cells decreased in the tested cases. To conclude, the SCV
      strains activate the PI3K-Akt signaling pathway in opposite to WT strains. This
      fact however did not influence the increase in the number of live SCV bacteria as
      compared to the WT strains. Knowing that the PI3K-Akt pathway is involved in
      proinflammatory cytokines suppression, SCVs seem to use this pathway to reduce
      the inflammatory response during the infection.

PMID- 29336621
TI  - Beta-Alanine Does Not Enhance the Effects of Resistance Training in Older Adults.
AB  - To investigate the potential of beta-alanine to increase muscular endurance of
      elder individuals in specific resistance-training protocols, we randomly assigned
      27 participants (60-82 years of age) to a 12-week double-blind intervention using
      3.2 g/day beta-alanine or placebo with or without resistance training to
      determine the effects on anthropometrics, muscular performance, and activities of
      daily living (ADL). The endurance-based resistance-training program (ERT) was
      given three times per week and included two sets of 15-25 repetitions on 11
      computerized pneumatic machines (alternating upper and lower body) at an
      intensity of 50% of maximum lifting weight (1RM). Mixed design analysis of
      variance (ANOVA) revealed no significant group * time interactions (p > .05) for
      any anthropometric or strength measures except 1RM leg press (p = .010). A post
      hoc analysis revealed significant improvements in 1RM leg press for both the
      resistance-training groups (p < .001) but no significant between-group difference
      attributable to beta-alanine. For the 20-repetition chest and leg press tests, no
      main effects of beta-alanine or group * time interactions for the exercise versus
      control groups were observed. Pairwise comparisons, however, did reveal
      significant improvements in peak and average power for both tests and fatigue
      index for the chest press in resistance-training groups. Although beta-alanine
      had no effect on any measures, the ERT program did positively affect three
      performance variables: 1RM, mechanical power, and fatigue patterns during
      muscular endurance testing. Future research should examine beta-alanine with
      different dosages and training programs to expand upon our findings using
      endurance-based resistance training.

PMID- 29336622
TI  - Nutritional Supplement and Functional Food Use Among Medical Students in India.
AB  - This study was conducted to assess the pattern of use of nutritional supplements
      (NSs) and functional foods (FFs), reasons for their use, factors influencing
      their use, and perception toward their use among medical students. Data were
      collected from 400 randomly chosen participants using a self-administered
      semistructured questionnaire. The most common source of information on these
      substances was from medical professionals (n = 140 [35%]). Multivitamins were
      consumed by 48 (45.3%) participants. Most common reasons stated for the use of
      supplements were for good health (n = 39 [36.8%]), doctor's prescription (n = 36
      [34%]), and to balance a poor diet (n = 34 [32.1%]). Sixty-six (62.3%) users used
      NSs on a daily or more than once daily basis. In 17.9% of the users, supplements
      were not recommended by a doctor or a dietician. The use of NSs was significantly
      more among females (p < .001), participants who exercised regularly (p < .001),
      participants who habitually skipped breakfast (p = 0.04), those with a family
      history of use of these products (p < .001), and those with "poor to fair" self
      rated health (p = .017). Use of FFs was associated with family history of use (p
      < .001) and intensity of exercise (p = .039). Participants who significantly used
      multiple NSs in this study were those who were vegetarians (p = .044) and those
      with "poor to fair" self-rated health (p = .047). Participants who used multiple
      FFs were female (p < .001). Only 18 (16.9%) users felt that regular use of NSs
      results in side effects. In multivariate analysis, family history of NS use was
      found to influence its usage among participants (p < 0.001). It is a matter of
      concern that there is lack of knowledge on NSs and FFs among medical students.
      Therefore, they need to learn more about the indications and the safety of
      prescription of these products.

PMID- 29336623
TI  - The Effect of Phytosterol-Rich Fraction from Palm Fatty Acid Distillate on Blood
      Serum Lipid Profile of Dyslipidemia Rats.
AB  - Phytosterol-rich fraction (PRF) obtained from palm fatty acid distillate (PFAD)
      was investigated for its effect on blood serum lipid profile of dyslipidemia
      rats. Dyslipidemia was induced by force feeding cholesterol to five groups of
      rats; one group was a control or normal group. Cholesterol force-fed groups were
      treated with 0, 10, 20, 30, and 40 mg PRF/kg/day for 4 weeks. All groups of rats
      were fed standard diet. A normal group was fed standard diet without PRF
      treatment and cholesterol force feeding. Lipid profile was measured every week
      (0, 1, 2, 3, and 4). Four-week treatment resulted in significant blood serum
      lipid profile improvement. PRF improved blood serum lipid profile by decreasing
      total cholesterol, triglyceride, and low density lipoprotein (LDL) cholesterol
      level and increasing high density lipoprotein (HDL) cholesterol level. The doses
      of PRF significantly affected blood serum lipid profile as well as duration of
      PRF treatment. PRF inhibited cholesterol absorption, which delayed blood serum
      total cholesterol rise. Cholesterol absorption inhibition was also indicated by
      higher fecal cholesterol concentration after PRF feeding. These results indicate
      the beneficial effect of PRF in the treatment of dyslipidemia.

PMID- 29336624
TI  - Potential Molecular Targets in the Treatment of Lung Cancer Using siRNA
      Technology.
AB  - Lung cancer is the leading cause of cancer-related mortality with about 1.6
      million deaths every year worldwide. Gene mutations and overexpression of
      oncogenes play a central role in malignant transformation in NSCLC. Conventional
      approaches for treatments of NSCLC have shown low levels of success while showing
      severe side effects. Target therapy using siRNA has recently emerged as a new
      strategy for cancer treatment by specific targeting of genes involved in the
      development and metastasis of cancer. This article dedicated to an update review
      of molecular targets could potentially be used for target therapy of lung cancer
      using SiRNA technology.

PMID- 29336625
TI  - The Clavien-Dindo Classification in Pancreatic Surgery: A Clinical and Economic
      Validation.
AB  - BACKGROUND/AIMS: In 2004 P. A. Clavien and D. Dindo published the well-known
      grading system of postoperative complications. It is established in several
      surgical disciplines. The aim of this study was to assess its validity in
      pancreatic surgery. The impact of complication grade on economic resources was
      investigated as well. METHODS: From a prospective database, we retrospectively
      evaluated all patients who underwent pancreatic resection between January 2009
      and December 2014 at our department. 309 patients received pancreatic head
      resection (pylorus-preserving pancreatoduodenectomy (PPPD) or Kausch-Whipple),
      total pancreatectomy or left resection. We performed a univariate analysis of the
      correlation between the Clavien-Dindo classification-grade (CDC-grade) with
      length of postoperative stay (LOS) and DRG-related (diagnosis related groups)
      remuneration using Kruskal-Wallis test. Furthermore, we performed a subgroup
      analysis (chi-square test and Fishers-test) of demographic, clinical, and
      perioperative data. RESULTS: American Society of Anesthesiologists (ASA) score (p
      = 0.0014), operation time (p = 0.0229) and intraoperative blood loss (p = 0.0016)
      showed significant correlation with CDC-grade. Increasing LOS and DRG-related
      remuneration correlated significantly with increasing CDC-grade (p < 0.0001).
      CONCLUSION: The CDC-grading system shows high correlation to clinical outcome and
      case-related remuneration in pancreatic surgery. Therefore, it is a valid tool
      for evaluation and comparison of surgical techniques and surgical centers.

PMID- 29336626
TI  - Antihypertensive monotherapy or combined therapy: which is more effective on
      functional status?
AB  - BACKGROUND: This study aims to analyze the effects of anti-hypertensive
      monotherapy and combined therapy on functional status, and cardiovascular risk
      outcomes in older adults. METHODS: This longitudinal non-randomized cohort study,
      involved hypertensive older adults (n = 440) aged 60 or more years with
      comorbidities. Participants underwent a community exercise training program and
      one of the following 2 conditions: i) use of daily mono-dose angiotensin
      converting enzyme inhibitors (ACEi; n= 232); ii) combined therapy including ACEi
      plus other class agent (Combined; n= 208). Baseline and 2-year follow-up
      evaluations included the functional fitness, health-related quality of life
      (HRQoL), health history questionnaires, anthropometric and hemodynamic profile.
      RESULTS: Both experimental groups have significantly improved physical functional
      status, and have significantly decreased blood pressure and waist circumference.
      ACEi group has significantly reduced body mass and body mass index, the Combined
      group significantly reduced the waist-to-hip ratio. Additionally, both groups
      perceived better physical HRQoL. CONCLUSIONS: Functional status has improved with
      ACEi medication and exercise training, regardless the ACEi medication therapy.
      Exercise training plus ACEi antihypertensive therapy should be recommended into
      the standard prescription practice to reduce the rate of physical disability
      among hypertensive older adults.

PMID- 29336627
TI  - Clinical Severity Classification using Automated Conjunctival Hyperemia Analysis
      Software in Patients with Superior Limbic Keratoconjunctivitis.
AB  - PURPOSE: Digitization of clinical observation is necessary for assessing the
      severity of superior limbic keratoconjunctivitis (SLK). This study aimed to use a
      novel quantitative marker to examine hyperemia in patients with SLK. MATERIALS
      AND METHODS: We included six eyes of six patients with both dry eye disease and
      SLK (SLK group) and eight eyes of eight patients with Sjogren syndrome (SS
      group). We simultaneously obtained the objective finding scores by using slit
      lamp examination and calculated the superior hyperemia index (SHI) with an
      automated conjunctival hyperemia analysis software by using photographs of the
      anterior segment. Three objective finding scores, including papillary formation
      of the superior palpebral conjunctiva, superior limbal hyperemia and swelling,
      and superior corneal epitheliopathy, were determined. The SHI was calculated as
      the superior/temporal ratio of bulbar conjunctival hyperemia by using the
      software. Fisher's exact test was used to compare a high SHI (>=1.07) ratio
      between the SLK and SS groups. P-Values < 0.05 were considered statistically
      significant. RESULTS: The SHI (mean +/- standard deviation) in the SLK and SS
      groups was 1.19 +/- 0.50 and 0.69 +/- 0.24, respectively. The number of patients
      with a high SHI (>=1.07) was significantly higher in the SLK group than in the SS
      group (p < 0.05). The sensitivity and specificity of the SHI in the differential
      diagnosis between SS and SLK were 66.7% and 87.5%, respectively. An analysis of
      the association between the objective finding scores and SHI showed that the SHI
      had a tendency to indicate the severity of superior limbal hyperemia and swelling
      score in the SLK group. CONCLUSION: The SHI calculated using the automated
      conjunctival hyperemia analysis software could successfully quantify superior
      bulbar conjunctival hyperemia and may be a useful tool for the differential
      diagnosis between SS and SLK and for the quantitative follow-up of patients with
      SLK.

PMID- 29336628
TI  - Effect of Multi-Ingredient Supplement Containing Satiereal, Naringin, and Vitamin
      D on Body Composition, Mood, and Satiety in Overweight Adults.
AB  - The purpose of this investigation was to examine the effects of 28 days of a
      dietary supplement on body composition, mood, and satiety in overweight adults.
      Twenty healthy adults (25.5 +/- 3.8 years; 87.3 +/- 20.7 kg; 169.9 +/- 10.6 cm;
      29.9 +/- 5.1 body mass index) participated in this randomized, double-blind,
      placebo-controlled investigation. Ten participants were provided with a dietary
      supplement containing 178 mg satiereal, 100 mg naringin, and 2,000 IU vitamin D3
      daily (SUPP), and ten participants were provided a placebo (PL) for 28 days.
      Baseline (PRE) and post (POST) assessments included body mass, BMI, and waist
      circumference measures. In addition, participants provided self-reported food
      records and completed study questionnaires twice weekly. Questionnaires consisted
      of profile of mood states, visual analog scales, modified trait food-cravings
      questionnaire, and a modified state food-cravings questionnaire. No significant
      differences were noted between groups for total calorie or macronutrient intake
      (p = 0.65-0.92), body mass (p = 0.34), BMI (p = 0.24), or waist circumference
      measures (p = 0.56-0.94). In addition, no significant differences between groups
      were observed for mood states, subjective measures of food cravings, or feelings
      of anxiety, fullness, bloating, hunger, craving, and stress (p >.05). In
      conclusion, 28 days of a dietary supplement containing satiereal, naringin, and
      vitamin D3 did not have any detectable beneficial effects on body-weight
      management.

PMID- 29336629
TI  - Pupillary manifestations of Marfan syndrome: from the Marfan eye consortium of
      Chicago.
AB  - BACKGROUND: Marfan syndrome (MFS) is a genetic disorder that affects multiple
      organ systems, including the eye. The most common ocular manifestations include
      ectopia lentis and retinal detachment. The current literature qualitatively cites
      that MFS patients have miotic or "poorly dilating" pupils. This study was the
      first to quantitatively assess pupillary function in MFS patients. MATERIALS AND
      METHODS: 57 eyes from 29 MFS patients, 36 eyes from 18 pediatric age- and gender
      matched controls, and 44 eyes from 22 adult age-matched controls were measured in
      a clinic-based cross sectional study. Pupillometry data were measured in scotopic
      conditions using the handheld NeurOptics PLR-200TM Pupillometer (NeurOptics,
      Irvine, CA, USA). Data obtained with the pupillometer were maximum and minimum
      diameter, constriction percentage, latency, average and maximum constriction
      velocities, average dilation velocity, and 75% recovery time (T75). RESULTS:
      Pediatric patients with MFS had significantly slower average constriction
      velocity measurements (beta = 0.65, p = 0.0003), maximum constriction velocity
      measurements (beta = 0.51, p = 0.0150) and average dilation velocity measurements
      (beta = -0.19, p = 0.0029) compared to control patients. In the adult cohort,
      results indicated significantly slower average dilation velocity measurements
      (beta = -0.13, p = 0.0077) compared to controls. CONCLUSIONS: Our data highlight
      pupillary parameters within a population of MFS patients under scotopic
      conditions. Constriction and dilation velocities were slower in the pediatric MFS
      patients compared to age- and gender-matched controls, and dilation velocities
      were slower in the adult MFS patients compared to age-matched controls. These
      findings, for the first time, quantitatively demonstrated differences in
      pupillary function in patients with MFS.

PMID- 29336630
TI  - Ameliorating Role of Lycopene, Tomato Puree, and Spirulina + Tomato Puree on the
      Hematology of Fluoride-Exposed Swiss Albino Mice.
AB  - Plant species rich in antioxidants (vitamins, flavonoids, lignans, and
      carotenoids) have been explored for complementary therapy of chronic diseases
      (cancers, coronary heart disease) and mitigation of pollutant toxicity. This
      article investigates their ameliorative role on selective hematological and serum
      biochemical parameters in fluoride-exposed (190 mg/kg body weight) Swiss albino
      mice pretreated with the antioxidant-rich diet supplements tomato puree (with and
      without peels), spirulina (cyanobacteria), and lycopene (present in tomato) for
      45 days prior to entry into experimental protocol. Compared with standard feed
      control, diet-modulated controls had more hairy and lustrous white fur,
      hemodilution, increase in platelet counts (2- to 5-fold), red blood cell (RBC)
      size (11%-14%), mean corpuscular hemoglobin (Hb) concentration (MCHC; 5%-14%),
      and serum albumin (23%-27%). Fluoride-exposed mice reared on standard feed had
      less hairy, pale white, lusterless fur and black nails, reduction in RBC and
      white blood cell (WBC) counts and Hb content, and morphological abnormalities in
      RBCs (poikilocytosis). By contrast, fur quality of fluoride-treated diet
      modulated groups was similar to standard feed control; counts and morphology of
      their RBCs and Hb content similar to the respective controls, and increase in WBC
      counts greater than controls. In comparison to the fluoride-treated standard feed
      group, platelet counts were higher in the treated mice of the diet-modulated
      groups. This study thus revealed the hemoprotective role of diet supplements in
      fluoride-treated mice. Considering the prevalence of fluoride-induced chronic
      toxicity in developing countries, our findings have relevance in minimizing
      hematological disorders among people residing in the fluoride-affected areas,
      because indigenously cultivated low-price tomato fruits are easily available for
      consumption.

PMID- 29336631
TI  - The Beneficial Radioprotective Effect of Tomato Seed Oil Against Gamma Radiation
      Induced Damage in Male Rats.
AB  - Radiation protection research receives intense focus due to its significant
      impact on human health. The present study was undertaken to investigate the
      protective effect of pretreatment with tomato seed oil (TSO) against gamma
      radiation-induced damage in rats. Male Wistar rats were divided into four groups:
      (1) untreated control; (2) TSO-supplemented; (3) gamma-irradiated; (4) TSO
      pretreated and gamma-irradiated. Acute exposure of animals to a single gamma
      radiation dose (6 Gy) induced oxidative stress in major body organs, altered
      serum lipid homeostasis, significantly increased serum testosterone and sorbitol
      dehydrogenase levels, and elicited a systemic inflammation as manifested by the
      induction of serum vascular cell adhesion molecule-1. Oral pretreatment with TSO
      (1 ml/kg; 3 times/week for 8 weeks) before exposure to gamma radiation protected
      rats against ionizing radiation-induced oxidative stress, restored lipid
      homeostasis, and suppressed systemic inflammation. Histological findings of
      target tissues verified biochemical data. The radioprotective ability of TSO was
      attributed to its content of phytosterols, policosanol, and antioxidants,
      including lycopene, beta-carotene, lutein, and tocopherols. TSO is considered a
      promising radioprotective agent that can be effectively used to protect the body
      from the damaging effects of harmful radiation.

PMID- 29336632
TI  - Mobius syndrome with cardiac rhabdomyomas.
AB  - BACKGROUND: Mobius syndrome is a rare congenital condition which presents not
      merely with 6th and 7th nerve palsies, but involves gaze paresis associated with
      craniofacial, limb, and other abnormalities. Heterogeneity is well known in
      patients with Mobius syndrome and rather than being of familial inheritance based
      on rare cases, it is much more recognized as a sporadic syndrome. We report an
      infant with features of congenital Mobius syndrome associated with cardiac
      rhabdomyomas in the absence of tuberous sclerosis. MATERIALS AND METHODS:
      Observational case report of an infant seen at a tertiary academic center with
      genetic testing, ophthalmic, neurological, and cardiac clinical examination and
      imaging. RESULTS: A newborn baby boy at birth was seen with multiple congenital
      craniofacial malformations, and respiratory distress. He was noted to have
      micrognathia, retrognathia, wide nasal bridge, low set ears, high arched palate,
      nonreducing bilateral talipes equinovarus and bilateral large angle esotropia
      with -4 abduction deficit and facial palsy, findings suggestive of Mobius
      Syndrome. MRI of the brain was unremarkable except for syringomyelia in the
      cervical spine. Echocardiography showed two cardiac rhabdomyomas in the right
      ventricle and ulltrasound of the abdomen showed mild right hydroneprosis.
      Cytogenetics revealed segmental loss at 21q21.2. Testing for tuberous sclerosis
      was negative for deletion or duplications of genes TSC1 and TSC2. CONCLUSION:
      This case highlights the rare co-occurrence of cardiac rhabdomyomas with Mobius
      syndrome and new segmental loss at 21q21.2 on genetic testing. Findings could
      indicate not a "suggestion of Mobius", but rather the syndrome itself in
      association with cardiac defects.

PMID- 29336633
TI  - The relationship between asthma and depression in a community-based sample.
AB  - OBJECTIVE: Asthma is an increasingly prevalent disease that is associated with
      substantial physical and financial burdens. Additionally, asthma is linked to
      psychiatric disorders. This study examines the relationship between asthma
      diagnosis, current depressive symptoms, and lifetime psychiatric disorder history
      in a large, community-based sample. METHODS: We analyzed data from 2168
      participants in the Dallas Heart Study, a large, diverse, community-based sample
      of people designed to be representative of the Dallas County population. Logistic
      regressions analyzing the relationship between asthma diagnosis and history of a
      psychiatric disorder, as well as between asthma diagnosis and the Quick Inventory
      of Depressive Symptomatology (QIDS) scores were performed, controlling for
      demographic data. RESULTS: 13.4% of the sample had an asthma diagnosis. Asthma
      diagnosis was significantly associated with a history of nervous, emotional, or
      mental health disorder diagnosis [OR 1.810 (95% CI 1.280-2.559) p = 0.001], and
      with QIDS scores consistent with moderate or greater current depressive symptom
      severity [OR 1.586 (95%CI 1.106-2.274) p = 0.012]. The relationships were not
      moderated by age, gender, race, smoking status, or Body Mass Index. CONCLUSIONS:
      A diagnosis of asthma may be associated with current clinically significant
      levels of depressive symptoms and a lifetime psychiatric disorder. The current
      report adds to the existing literature in this area by assessing both current and
      lifetime symptoms and by using a large and diverse population. The findings
      highlight the clinical importance of considering the possibility of psychiatric
      illness in asthma patients and suggest further research in this area is needed.

PMID- 29336634
TI  - sICAM-1, sVCAM-1 and sE-Selectin Levels in Type 1 Diabetes.
AB  - BACKGROUND/OBJECTIVE: This study was performed to compare soluble levels of
      adhesion molecules between diabetic patients and controls and to assess their
      possible association with long-term complications of type 1 diabetes (T1D).
      METHODS: Forty-eight patients with T1D and 39 healthy controls were enrolled in
      this study. The plasma level of adhesion molecules was measured by sandwich
      enzyme-linked immunosorbent assay technique. RESULTS: Higher sVCAM 1 (soluble
      vascular cell adhesion molecule 1) levels correlated with older age of onset of
      T1D. The plasma level of sICAM 1 (soluble intercellular adhesion molecule 1) was
      significantly increased, while sE selectin was significantly decreased in
      patients with T1D, compared to controls. There was no significant relationship
      between these plasma-level variations and the long-term complications of T1D.
      CONCLUSION: Although plasma levels of cell adhesion molecules are different in
      T1D patients and healthy controls, they might not be good candidate markers for
      prognosis of disease.

PMID- 29336635
TI  - Lymphomatoid Granulomatosis in a 14-Year-Old Boy with Trisomy 21 and History of B
      Lymphoblastic Leukemia/Lymphoma.
AB  - BACKGROUND: Lymphomatoid granulomatosis is a EBV-driven lymphoproliferative
      disorder that has been reported in association with immunodeficiency, but only
      exceptionally in patients with hematopoietic malignancy. CASE REPORT: A 14-year
      old boy with trisomy-21 and a history of B-lymphoblastic leukemia/lymphoma (B
      ALL) diagnosed 1.5 years prior, on maintenance chemotherapy, presented with fever
      and respiratory symptoms. Chest X-ray revealed right-lower-lobe consolidation. He
      was treated for pneumonia but continued to be febrile with worsening respiratory
      status, with development of additional pulmonary and liver nodules. No infectious
      etiology was identified. Following nondiagnostic lung and liver biopsies, the
      largest pulmonary mass was resected. The histopathologic findings were diagnostic
      of lymphomatoid granulomatosis. There was no residual B-ALL. The patient's status
      continued to deteriorate and he died shortly thereafter. CONCLUSION: Relative
      immunosuppression due to maintenance therapy for B-ALL can lead to lymphomatoid
      granulomatosis.

PMID- 29336636
TI  - A Dysmorphology Based Systematic Approach Toward Perinatal Genetic Diagnosis in a
      Fetal Autopsy Series.
AB  - BACKGROUND: This retrospective study assesses the contribution of genetic
      disorders in fetuses undergoing postmortem evaluation and the performance of a
      clinical dysmorphology based systematic approach toward genetic diagnosis.
      MATERIALS AND METHODS: Ninety fetuses, including spontaneous losses and
      terminated pregnancies, underwent a postmortem evaluation including
      dysmorphological examination, radiological studies, and histopathological
      examination. Genetic testing including karyotyping, biochemical testing, Sanger
      sequencing, and exome sequencing were performed selectively. RESULTS: A genetic
      etiology was concluded in 48 fetuses (55%). As a standalone test,
      dysmorphological examination was able to ascertain a definite genetic diagnosis
      in sixteen cases, histopathology in six; and karyotyping, biochemical testing and
      exome sequencing in two cases each (Total 28). Additionally, dysmorphology
      findings indicated possible genetic disorder in 20 cases. CONCLUSION: Genetic
      etiologies contribute significantly to fetuses undergoing autopsy in this series.
      A systematic approach to postmortem fetal evaluation guided by dysmorphological
      examination provides high diagnostic yield toward perinatal genetic diagnosis.

PMID- 29336637
TI  - Post Mortem Diagnosis of Blake's Pouch Cyst: A Presentation of Distended Cyst at
      Necropsy.
AB  - BACKGROUND: Blake's pouch cyst forms from non-permeabilization of Blake's pouch.
      It is difficult to visualize at necropsy as the cyst ruptures easily into the 4th
      ventricle during dissection. CASE REPORT: Based upon prenatal imaging, delicate
      dissection allowed post-mortem confirmation of the Blake's pouch cyst.
      CONCLUSIONS: This highlights the importance of utilizing premortem imaging to
      help guide the postmortem dissection and documentation of a posterior fossa cyst.

PMID- 29336638
TI  - Prehospital Administration of Epinephrine in Pediatric Anaphylaxis - A Statewide
      Perspective.
AB  - OBJECTIVE: Timely administration of epinephrine is critical in the treatment of
      anaphylaxis. This study sought to determine the frequency of administration of
      epinephrine by EMS providers caring for pediatric patients in the prehospital
      setting. METHODS: We examined data from the NC EMS database (PreMIS) from 2010-3
      to determine frequency of epinephrine administration in pediatric patients with
      anaphylaxis. We studied patients <18 years of age with an EMS provider impression
      of "allergic reaction." Anaphylaxis was present if there was hypotension (defined
      as SBP < 90 or DBP < 45 for patients age 11 and older, and SBP < 70 + (2 * age)
      for patients ages 0-10), or impaired respirations (defined as description of
      labored or absent respirations, or RR < 12 or > 30). We determined the overall
      frequency of epinephrine administration. A multivariate logistic regression was
      then constructed to examine the impact of the following variables on appropriate
      epinephrine administration: age < 10, non-white race, rural county of case
      origin, duration of transportation from scene, and presence of a paramedic.
      RESULTS: A total of 504 patients met inclusion criteria, of which 471
      demonstrated anaphylaxis as previously defined. A total of 153 patients with
      anaphylaxis received epinephrine (32.4%, 95% CI 28.3-36.9%). Age < 10 was
      associated with increased odds of not receiving epinephrine appropriately (OR
      2.90, 95% CI 1.85-4.54, p < 0.001). Other variables did not have statistically
      significant impact on epinephrine administration. CONCLUSION: There are missed
      opportunities for prehospital administration of epinephrine in pediatric patients
      with anaphylaxis. Very young children (age < 10) had increased odds for not
      receiving epinephrine.

PMID- 29336639
TI  - Intellectual, educational, and situation-based social outcome in adult survivors
      of childhood medulloblastoma.
AB  - PURPOSE: To investigate intellectual and situation-based social outcome and
      educational achievement in adult survivors of childhood medulloblastoma and
      analyse factors influencing outcome Methods: We collected demographic, medical
      and cognitive data, and social and educational outcome at a mean time since the
      end of treatments of 14.9 years in 58 adults, aged 19-35 years, consecutively
      treated in a single cancer center between 1989 and 2005. RESULTS: Ten survivors
      had severe intellectual disability, 12 were still studying, 23 had a regular
      employment and 13 were unemployed. Full Scale Intellectual Quotient, assessed 6.6
      years after the end of treatments, ranged from 46 to 131. It was strongly
      associated with educational achievement and significantly lower in patients who
      experienced postoperative cerebellar mutism, and when parental education level
      was low. CONCLUSION: These factors should be systematically considered at
      diagnosis in order to offer adequate and timely assessments and interventions.

PMID- 29336640
TI  - Novel RNASET2 Pathogenic Variants in an East Asian Child with Delayed Psychomotor
      Development.
AB  - INTRODUCTION: RNASET2 mutation has been reported in patients with cystic
      leukoencephalopathy without megalencephaly and the Aicardi-Goutieres syndrome.
      Both disorders are Mendelian mimics of congenital cytomegalovirus infection with
      overlapping features, including leukoencephalopathy, white matter alterations,
      intracranial calcification, delayed psychomotor development, intelligence
      disability and seizures. Only eight families with RNASET2 mutation have been
      previously reported. METHODS: Whole exome sequencing was performed and copy
      number variants were described by read-depth strategy. RESULTS: We identified a
      novel nonsense variant c.128G>A (p. W43*) and a 430 Kb 6q27 microdeletion
      encompassing RNASET2. Our patient did not show anterior temporal lobe subcortical
      cysts, hearing loss, dystonia or extra-neurological features. CONCLUSION: Our
      results provided further genetic and phenotypic information of RNASET2 mutation
      in Chinese patients and highlighted the importance for physicians to consider
      RNASET2-related disorders when diagnosing patients with congenital brain
      infection-like phenotypes.

PMID- 29336641
TI  - Impact of Forward and Backward Scattering and Corneal Higher-Order Aberrations on
      Visual Acuity after Penetrating Keratoplasty.
AB  - PURPOSE: To assess the relationship of forward and backward scattering and
      corneal higher-order aberrations (HOAs) with corrected distance visual acuity
      (CDVA) after penetrating keratoplasty (PK). METHODS: This retrospective study
      comprised 25 eyes of 25 consecutive patients who underwent PK using the VisuMax
      femtosecond laser system and age-matched 25 eyes of 25 healthy subjects. We
      quantitatively assessed objective scattering index (OSI) using the double-pass
      instrument (OQAS II, Visiometrics), corneal densitometry (CD) and corneal HOAs
      with the Scheimpflug rotating camera (Pentacam HR, Oculus) 1 year
      postoperatively. RESULTS: The OSI, CD, and corneal HOAs were significantly larger
      in the PK group than those in the control group (p <= 0.011). We found
      significant correlations of logMAR CDVA with the OSI (r = 0.477, p = 0.016), and
      with the anterior, posterior, and total corneal HOAs of the central 4-mm zone
      (anterior: r = 0.573, p = 0.003, posterior: r = 0.596, p = 0.002, total: r =
      0.472, p = 0.017), but no significant association with the CD of the 0-2 mm zone
      at any layers (anterior: r = 0.236, p = 0.257, center: r = 0.139, p = 0.506,
      posterior: r = 0.073, p = 0.728, total: r = 0.212, p = 0.308). Similar results
      were obtained when the analysis was repeated with corneal HOAs of the central 6
      mm zone and CDs in 2-6 mm zone. CONCLUSIONS: Our pilot study demonstrated that
      the postoperative CDVA was significantly correlated with OSI and corneal HOAs,
      but not with backward scattering in post-PK eyes, suggesting that OSI as well as
      corneal HOAs plays an essential role in postoperative visual performance after
      PK.

PMID- 29336642
TI  - Concurrent Validity of Two Gait Performance Measures in Children with Neuromotor
      Disorders.
AB  - AIMS: To investigate the concurrent validity of two mobility performance
      measures, the Functional Mobility Scale (FMS) and the Gillette Functional
      Assessment Questionnaire - walking scale (FAQ) in an inpatient pediatric
      neurorehabilitation setting. METHODS: Cross-sectional data were collected on 71
      children (mean age 12.7 years) with neuromotor gait impairments who participated
      in an inpatient rehabilitation program to evaluate aspects of concurrent validity
      of the FMS and FAQ. Physiotherapists independently performed ratings. Comparator
      instruments included the walking item of the Functional Independence Measure for
      children, 10-m and 6-minute walking tests, and Gross Motor Function Measure-88
      dimension E. All tests were completed within 7 days. Spearman correlation
      coefficients were calculated to test a priori formulated hypotheses regarding the
      strength and direction of the measures relationships. RESULTS: The children had a
      broad spectrum of mobility levels, including all levels of FMS and levels 2-10 of
      FAQ. Spearman correlation coefficients with comparator measures varied between
      0.58-0.79 for the FMS and 0.69-0.73 for the FAQ. Hypotheses concerning
      correlation strengths and directions were met for FMS and FAQ. CONCLUSIONS: The
      findings demonstrate that the FMS and FAQ are valid to evaluate functional
      mobility in pediatric inpatient neurorehabilitation.

PMID- 29336643
TI  - Measurement of Fetal Mesencephalon and Pons Via Ultrasonographic Cross Sectional
      Imagining.
AB  - OBJECTIVES: This study evaluated the feasibility of measuring the fetal
      mesencephalon and pons by ultrasonographic cross sectional imaging to detect
      fetal central nervous system developmental abnormalities. MATERIALS AND METHODS:
      Fetal ultrasonographic measurements included: Fetal mesencephalon anteroposterior
      diameters (MAD), mesencephalon transverse diameters (MTD), pons anteroposterior
      diameter (PAD) and proximal transverse diameters (PTD). RESULTS: Nine-hundred
      ninety fetuses were imaged. Thirty-eight fetuses (observation group) presented
      central nervous system abnormalities; 952 fetuses without imaged abnormalities
      were utilized as the reference (control) group. Fetal MAD, MTD, PAD, and PTD in
      control fetuses showed a linear correlation with gestational age. Thirty-eight
      fetuses had 40 abnormal measurements (8 MAD, 8 MTD, 14 PAD, and 10 PTD), 16 in
      mesencephalon, and 24 in pons. All data fell below the 95% confidence intervals'
      lower limits for the corresponding gestational age. CONCLUSION: Using normative
      data based on 957 fetuses allows detection of size abnormalities of the pons and
      midbrain during fetal life.

PMID- 29336644
TI  - Evidence, education and multi-disciplinary integration are needed to embed
      exercise into lung cancer clinical care: A qualitative study involving
      physiotherapists.
AB  - AIMS: To explore physiotherapists perceptions regarding barriers and enablers to
      embedding exercise into routine lung cancer clinical care. DESIGN: Qualitative
      study (content analysis). Eight physiotherapists working in the area of lung
      cancer at five hospitals participated. The focus group was conducted, transcribed
      verbatim and independently crosschecked. Thematic analysis was utilized. RESULTS:
      The data generated four major themes: evidence justifying exercise; staffing and
      services; maximising the efficacy of interventions; and hospital culture.
      Physiotherapists perceived that barriers included lack of evidence, lack of
      physiotherapy time and funding, inconsistencies in patient access to outpatient
      exercise programs, lack of clear referral pathways, limited knowledge about
      exercise by the wider multi-disciplinary team, and poor culture of physical
      activity in the inpatient setting. Recommendations included developing a stronger
      evidence-base, establishing set patient pathways into exercise programs, re
      allocating physiotherapy services to high-risk patients, and
      integrating/involving the multi-disciplinary team particularly through education
      and communication. CONCLUSION: This study has identified barriers to, and
      potential strategies for, the embedding of exercise into lung cancer clinical
      practice. Evidence, education and multi-disciplinary integration are viewed by
      physiotherapists as critical for success. A targeted gradual approach, by
      applying these strategies at defined stages across the lung cancer pathway, is
      recommended to facilitate future practice change.

PMID- 29336645
TI  - Physical exercise prior to hematopoietic stem cell transplantation: A feasibility
      study.
AB  - PURPOSE: This study explores the feasibility and preliminary effectiveness of an
      exercise program in people scheduled for hematopoietic stem cell transplantation
      (HSCT). METHODS: In this controlled clinical trial, we compare pre
      transplantation exercise to no exercise in the waiting period for an allogeneic
      of autologous HSCT. The supervised individually tailored exercise program (4-6
      weeks) consisted of aerobic endurance, muscle strength, and relaxation exercises,
      administered twice a week in the period prior to HSCT. Feasibility was determined
      based on inclusion rate, attrition rate, adherence to intervention, safety, and
      satisfaction (0-10). Preliminary effectiveness was determined primarily by self
      perceived physical functioning, quality of life (QOL), and fatigue. Secondary
      outcomes were global perceived effect (GPE), blood counts, hospital stay, and
      physical fitness. RESULTS: Forty-six patients were eligible, of whom 29 (69%)
      participated: 14 in the intervention group and 15 in the control group. The
      adherence rate to training was 69%. No adverse events or injuries occurred.
      Satisfaction of training conditions was high (mean 9.2 +/- 1.3). Positive (follow
      up) trends in favor of the intervention group were found for self-perceived
      physical functioning, QOL, fatigue, GPE, blood counts, and hospital stay.
      CONCLUSION: Exercise prior to HSCT is safe and feasible, and positive trends
      suggest favorable preliminary effectiveness. Adherence to the exercise program
      needs to be optimized in a future trial.

PMID- 29336646
TI  - Anti-cyclic citrullinated peptide antibodies, other common autoantibodies, and
      smoking as risk factors for lymphoma in patients with rheumatoid arthritis.
AB  - OBJECTIVES: Patients with rheumatoid arthritis (RA) are at increased risk of
      lymphoma. There is no biomarker to indicate future lymphoma risk in RA and it is
      not known whether factors associated with an increased risk of RA also confer an
      increased risk of lymphoma. We investigated whether anti-cyclic citrullinated
      peptide (CCP) antibodies, other autoantibodies, and smoking, are associated with
      lymphoma development in RA. METHOD: From two population-based case-control
      studies, the Scandinavian Lymphoma Etiology (SCALE) study and the Epidemiological
      Investigation of Rheumatoid Arthritis (EIRA) I study, we identified lymphoma
      cases with a validated RA diagnosis (n = 50), to whom we matched study
      participants with RA but no lymphoma (n = 261), lymphoma but no RA (n = 257), and
      neither RA nor lymphoma (n = 233). Lymphomas were classified according to the WHO
      classification. Blood samples were analysed for immunoglobulin G (IgG), IgM, and
      IgA isotypes and IgG1-4 subclasses of anti-CCP antibodies and for 15 antinuclear
      antibody (ANA)-associated specific autoantibodies. Relative risks were estimated
      as crude and adjusted odds ratios (adjOR) with 95% confidence intervals (CIs)
      using logistic regression. RESULTS: We found no association between anti-CCP IgG
      >= 25 units/mL (adjOR 1.4, 95% CI 0.7-2.7), anti-CCP IgG >= 500 units/mL (adjOR
      1.4, 95% CI 0.7-3.0), anti-CCP Ig of other isotypes, other autoantibodies (adjOR
      any vs none 0.6, 95% CI 0.3-1.2), or cigarette smoking (adjOR ever vs never 1.1,
      95% CI 0.5-2.2) and lymphoma risk among patients with RA. CONCLUSION: In this
      study, neither anti-CCP antibodies (IgG, IgG1-4, IgM, or IgA), nor other common
      autoantibodies, nor smoking predicted lymphoma risk in RA.

PMID- 29336647
TI  - Inflammatory Myofibroblastic Tumor of the Tongue. Report of a Pediatric Case and
      Review of the Literature.
AB  - BACKGROUND: Inflammatory myofibroblastic tumor (IMT) is an uncommon mesenchymal
      lesion composed of myofibroblastic and fibroblastic spindle cells, accompanied by
      inflammatory infiltration. IMT may occur in the tongue. Five cases have been
      previously reported at this site. CASE REPORT: An inflammatory myofibroblastic
      tumor arose in the tongue of a 10 month old infant, confirmed by anaplastic
      lymphoma kinase (ALK) immunohistochemical staining and the clinical response to
      the tyrosine kinase inhibitor. CONCLUSIONS: IMT can occur in the tongue. This
      report highlights the differential diagnosis of IMT. ALK staining is both a
      helpful diagnostic marker and a predictive marker for targeted therapy in this
      tumor type.

PMID- 29336648
TI  - Rhythmic arm swing integrated into treadmill training in patients with chronic
      stroke: A single-subject experimental study.
AB  - Normal walking includes coordinated and controlled movement of the legs and arms.
      However, patients following stroke often present with inappropriate motor control
      which limits coordinated movement patterns of the affected limbs. This study
      aimed to compare the effects of rhythmic arm swing and arm fixation during
      treadmill walking in patients with poststroke hemiparesis. We used an alternating
      study design with multiple baselines across subjects. Three patients with chronic
      stroke participated in this study. During treadmill walking, rhythmic arm swing
      and arm fixation conditions were alternately applied. Outcome measures included
      the 10-meter walk test (10MWT) and energy expenditure index (EEI). In the
      intervention phase, all subjects showed significantly greater improvements in the
      10MWT and EEI scores for rhythmic arm swing condition compared to those for arm
      fixation condition (p < 0.05). 10MWT improvement rates: Subject 1-34.81% vs.
      15.75%; Subject 2-40.00% vs. 17.95%; and Subject 3-38.08% vs. 21.85%; and EEI
      improvements: Subject 1-23.19% vs. 14.08%; Subject 2-26.15% vs. 20.43%; and
      Subject 3-22.99% vs. 14.49%. These findings suggest that rhythmic arm swing is
      clinically feasible as a more favorable option to enhance the effects of
      treadmill walking training. However, larger studies with a different study design
      are needed to be able to make any judgment about the usefulness of the treatment.

PMID- 29336649
TI  - Severe Craniofacial Involvement due to Amniotic Band Sequence.
AB  - BACKGROUND: Disruptive amniotic band sequence (DABS) is a sporadic, non-familial
      disorder with unclear etiology. Diagnosis is based on clinical features because
      there is currently no reliable laboratory diagnostic tests. OBJECTIVE: We
      describe six cases of DABS with severe craniofacial deformations, three with and
      three without classical constrictive limb deformation. RESULTS: The craniofacial
      deformities were delimited by peripheral sharply demarcated scarring. CONCLUSION:
      When a sharply demarcated linear disruptive craniofacial lesion is observed, DABS
      should be considered despite the absence of constrictive limb scarring.

PMID- 29336650
TI  - Association of REL Polymorphism with Cow's Milk Proteins Allergy in Pediatric
      Algerian Population.
AB  - INTRODUCTION: Cow's milk proteins allergy (CMPA) pathogenesis involves complex
      immunological mechanisms with the participation of several cells and molecules
      involved in food allergy. The association of polymorphisms in the interleukin 4,
      Forkhead box P3 and the avian reticuloendotheliosis genes was investigated in an
      infant population with CMPA of Western Algeria. MATERIALS AND METHODS: We
      obtained DNA and clinical data from milk allergic subjects during active phase
      and from a group of non-atopic control subjects. RESULTS: Our findings showed
      that the allele G of the cRel gene intronic polymorphism at +7883 positions was
      significantly higher among cow's milk proteins allergic patients compared to
      control subjects. CONCLUSION: The results of this study suggest a possible
      association of CMPA with cRel G+7883T polymorphism.

PMID- 29336651
TI  - Formal and Informal Control of Cannabis: Regular Users' Experience.
AB  - BACKGROUND: The debate on recreational use of cannabis, recently relaunched by
      the election of the Liberal Party of Canada that intends to legalize and regulate
      its use and access, implies a better understanding of social control mechanisms
      that are in place, and their influence on users' behaviors. OBJECTIVE: This study
      addresses the issue of formal and informal controls by providing, first, a
      theoretical perspective of this concept, and, second, by illustrating its
      operation from the users' perspective. METHODS: Semi-structured interviews were
      conducted with 164 regular, adult cannabis users recruited in four large Canadian
      cities (Vancouver, Toronto, Montreal, and Halifax). An initial qualitative
      analysis based on the principles of grounded theory was conducted. The main
      categories identified were then used to find and re-code relevant material on the
      respondents' experience with formal and informal control (secondary analysis).
      RESULTS: The users' perspective shows that mechanisms of informal control play an
      important role in defining the social context of their use (when, where, and with
      whom cannabis is consumed). In contrast, formal control had no deterrent impact
      on the cessation or reduction of use, but affected their behavior by influencing
      them to change the context of their practices to avoid criminal legal
      consequences and stigmatization. Conclusions/Importance: The regulatory controls
      based in public health that the Canadian government plans to implement (replacing
      criminal ones), should be based on a better understanding of current practices
      and patterns of cannabis users, and in accordance with informal controls already
      in place. Legislative formal controls, in a regulatory model, that are better
      defined and consistent with social practices, will be more accepted and respected
      by the user population and thus likely to be more effective in reducing harm.

PMID- 29336652
TI  - Detection of STEMI Using Prehospital Serial 12-Lead Electrocardiograms.
AB  - OBJECTIVE: Repeated or serial 12-lead electrocardiograms (ECGs) in the
      prehospital setting may improve management of patients with subtle ST-segment
      elevation (STE) or with a ST-segment elevation myocardial infarction (STEMI) that
      evolves over time. However, there is a minimal amount of scientific evidence
      available to support the clinical utility of this method. Our objective was to
      evaluate the use of serial 12-lead ECGs to detect STEMI in patients during
      transport in a Canadian emergency medical services (EMS) jurisdiction. METHODS:
      We performed a retrospective study of suspected STEMI patients transported by EMS
      in the Chaudiere-Appalaches region (Quebec, Canada) between August 2006 and
      December 2013. Patients were monitored by a serial 12-lead ECG system where an
      averaged ECG was transmitted every 2 minutes. Following review by an emergency
      physician, ECGs were grouped as having either a persistent STE or a dynamic STE
      that evolved over time. RESULTS: A total of 754 suspected STEMI patients were
      transported by EMS during the study period. Of these, 728 patients met
      eligibility criteria and were included in the analysis. A persistent STE was
      observed in 84.3% (614/728) of patients, while the remaining 15.7% (114/728) had
      a dynamic STE. Among those with dynamic STE, 11.1% (81/728) had 1 ST-segment
      change (41 no-STEMI to STEMI; 40 STEMI to no-STEMI) and 4.5% (33/728) had >= 2 ST
      segment changes (17 no-STEMI to STEMI; 16 STEMI to no-STEMI). Overall, in 8.0%
      (58/728) of the cohort, STEMI was identified on a subsequent ECG following an
      initial no-STEMI ECG. CONCLUSIONS: Through recognition of transient ST-segment
      changes during transport via the prehospital serial 12-lead ECG system, STEMI was
      identified in 8% of suspected STEMI patients who had an initial no-STEMI ECG. Key
      words: electrocardiography; emergency medical services; ST-elevation myocardial
      infarction; prehospital dynamic ECG.

PMID- 29336653
TI  - Assessment of spatial heterogeneity in continuous twin screw wet granulation
      process using three-compartmental population balance model.
AB  - In this study, a novel three-compartmental population balance model (PBM) for a
      continuous twin screw wet granulation process is developed, combining the
      techniques of PBM and regression process modeling. The developed model links
      screw configuration, screw speed, and blend throughput with granule properties to
      predict the granule size distribution (GSD) and volume-average granule diameter.
      The granulator screw barrel was divided into three compartments along barrel
      length: wetting compartment, mixing compartment, and steady growth compartment.
      Different granulation mechanisms are assumed in each compartment. The proposed
      model therefore considers spatial heterogeneity, improving model prediction
      accuracy. An industrial data set containing 14 experiments is applied for model
      development. Three validation experiments show that the three-compartmental PBM
      can accurately predict granule diameter and size distribution at randomly
      selected operating conditions. Sixteen combinations of aggregation and breakage
      kernels are investigated in predicting the experimental GSD to best judge the
      granulation mechanism. The three-compartmental model is compared with a one
      compartmental model in predicting granule diameter at different experimental
      conditions to demonstrate its advantage. The influence of the screw
      configuration, screw speed and blend throughput on the volume-average granule
      diameter is analyzed based on the developed model.

PMID- 29336654
TI  - Serotonin Syndrome in Tapentadol Literature: Systematic Review of Original
      Research.
AB  - The potential association between serotonin syndrome and tapentadol is not well
      described in the literature. This study aimed to review the literature and
      identify methodological issues that could lead to inaccurately reported rates of
      serotonin syndrome associated with tapentadol use. A systematic review of English
      articles using MEDLINE, Cochrane Controlled Trials Register, and Scopus was
      performed. Additional studies were identified by cross-referencing article
      bibliographies. Original research that examined the safety of tapentadol in
      patients with nonconfounding indications were examined. In total, 22 studies met
      inclusion criteria. There were 13 randomized clinical trials, 7 open-label
      trials, and 2 observational studies. All studies either did not mention whether
      serotonergic medication use was prohibited or disallowed use. Frequently reported
      adverse events were nausea, diarrhea, constipation, fatigue, vomiting, and
      somnolence. No studies reported serotonin syndrome development. No included
      trials differentiated between the development of adverse events in patients
      taking serotonergic drugs and those who were not. This differentiation is
      necessary to evaluate the increased risk of adverse events in patients prescribed
      tapentadol concomitantly with other serotonergic medications. Therefore, the
      current tapentadol literature has important limitations that prevent the adequate
      characterization of the potential association between tapentadol and serotonin
      syndrome.

PMID- 29336655
TI  - Reversible cicatricial ectropion associated with EGFR inhibitors.
AB  - The management of cicatricial ectropion resulting from epidermal growth factor
      receptor (EGFR) inhibitors is unclear. We describe two cases of bilateral
      cicatricial ectropion following the use of an EGFR inhibitor who were treated
      with oral doxycycline, topical ophthalmic steroid and antibiotic ointment to the
      eyelids, and topical facial steroid cream with lubrication. The first case
      resolved with discontinuation of panitumumab infusions along with institution of
      the aforementioned regimen. However, it is unclear whether the resolution was
      from discontinuation of the infusions or from the instituted regimen. The second
      case resolved without a dose adjustment of cituximab. This case may provide
      support for the use of this regimen prior to discontinuation of the offending
      agent, as there was a successful outcome without alteration of the infusions.
      Additional cases are necessary to determine if this is a successful means of
      treating bilateral lower-lid cicatricial ectropion from EGFR inhibitors.

PMID- 29336656
TI  - The use of mastoid vibration with canalith repositioning procedure to treat
      persistent benign paroxysmal positional vertigo: A case report.
AB  - The Canalith Repositioning Procedure (CRP) was originally described as a non
      invasive treatment for Benign Paroxysmal Positional Vertigo (BPPV) by Epley.
      Since its inception, the maneuver has undergone several modifications; and
      currently is performed in the absence of induced mastoid vibration (oscillation).
      Clinically, mastoid vibration may be used to assist in treatment of persistent
      cases of BPPV, where a simple CRP may fail to improve symptoms. This case
      describes a patient with a three-month history of BPPV (right posterior
      canalithiasis), who was previously treated unsuccessfully with standard CRP.
      Mastoid vibration was introduced as part of the treatment due to persistent BPPV.
      After one treatment utilizing CRP with mastoid vibration, the patient had
      complete resolution of symptoms, and remained symptom free at a six-month follow
      up. It can be concluded that introducing mastoid oscillation via vibration to the
      CRP in persistent cases of semicircular canalithiasis BPPV may produce positive
      patient outcomes.

PMID- 29336657
TI  - What Factors are Associated with Electronic Cigarette, Shisha-Tobacco and
      Conventional Cigarette Use? Findings from a Cross-Sectional Survey of Australian
      Adolescents?
AB  - BACKGROUND: Adolescents' use of electronic cigarettes and shisha-tobacco
      increased in several countries during the 2000s, including in the United States,
      United Kingdom and Canada. Few studies have examined the factors associated with
      exclusive e-cigarette or shisha-tobacco use and whether adolescents using these
      substances exclusively differ from those using traditional cigarettes.
      OBJECTIVES: To examine the socio-demographic and behavioural correlates of
      exclusive e-cigarette and exclusive shisha-tobacco use to those found for users
      of tobacco cigarettes and multiple nicotine products in Australian adolescents.
      METHODS: Cross-sectional survey of smoking behaviours of a random sample of 4,576
      students in the Australian state of Victoria aged 12-17 conducted between June
      2014 and December 2014. RESULTS: Overall, 14% of students had used an e-cigarette
      with 3% using e-cigarettes exclusively. 13% had used shisha-tobacco, with 2%
      using shisha-tobacco exclusively. Most students (65%) using e-cigarette and
      shisha-tobacco (67%) had also used tobacco cigarettes. After adjusting for
      demographic factors, students using e-cigarettes only were more likely to have
      never used cannabis or drink alcohol in the past year compared to tobacco
      cigarette users. Compared to tobacco cigarette users, students using only shisha
      tobacco were younger, less likely to use cannabis or alcohol or have friends or
      parents who smoke. CONCLUSIONS: Most Australian adolescents who use alternative
      nicotine and tobacco-related products do so in conjunction with tobacco
      cigarettes. Students using e-cigarettes or shisha-tobacco exclusively were less
      likely to use other substances. Australian longitudinal studies are needed to
      determine whether this group of students are on a pathway to traditional tobacco
      use.

PMID- 29336658
TI  - Just a First-Year Thing? The Relations between Drinking During Orientation Week
      and Subsequent Academic Year Drinking Across Class Years.
AB  - BACKGROUND: The goal of Orientation Week is to help new students adjust to
      university life. However, it is a period when many new students engage in
      excessive alcohol consumption and where problematic drinking patterns may be
      established. OBJECTIVE: The objective is to determine whether returning students
      drink in a similar manner to students in their first-year of classes and whether
      Orientation Week drinking predicts semester drinking more strongly for first-year
      than returning students. METHODS: We tested 552 students (18 to 25 years old) in
      their first, second, or third class year of university. Students reported their
      Orientation Week drinking and then completed daily drinking diaries for 13
      consecutive days during the academic year. RESULTS: Orientation Week drinking was
      similar across class years and also predicted academic year drinking for students
      in all class years. Conclusion/Importance: Drinking during Orientation Week is
      not just a first-year problem and prevention efforts should focus on all
      students.

PMID- 29336659
TI  - Long non-coding RNA HOTAIR promotes cervical cancer progression through
      regulating BCL2 via targeting miR-143-3p.
AB  - BACKGROUND: HOX transcript antisense RNA (HOTAIR) is a long non-coding RNA
      (lncRNA) widely involved in the progression of numerous malignancies. Whereas,
      the potential molecular mechanism of HOTAIR involved in cervical cancer
      progression is still needed to be elaborated. METHODS: The expression of HOTAIR
      and miR-143-3p were detected in cervical cancer tissues and cells by qRT-PCR. MTT
      and flow cytometry analysis were performed to measure cell proliferation and
      apoptosis. Bioinformatics, Dual-Luciferase reporter and RIP were used to analyze
      the possible correlation between HOTAIR, miR-143-3p and BCL2. The expression of
      Bax and BCL2 was detected by western blot. Mice xenograft model was established
      to confirm the role of HOTAIR on tumor growth in vivo. RESULTS: HOTAIR expression
      was elevated while miR-143-3p expression was reduced in cervical cancer tissues
      and cell lines. HOTAIR knockdown suppressed proliferation and enhanced apoptosis
      in cervical cancer cells. Moreover, HOTAIR could function as a sponge for miR-143
      3p. The inhibitory effect of HOTAIR knockdown on cervical cancer cells growth was
      abolished following decrease of miR-143-3p expression. Furthermore, HOTAIR
      promoted BCL2 expression by modulating miR-143-3p. BCL2 overexpression attenuated
      the tumor-suppressive effect of miR-143-3p in cervical cancer. Finally, the
      carcinogenicity of HOTAIR was validated in mice. CONCLUSIONS: HOTAIR promoted
      cervical cancer cell growth by modulating BCL2 via miR-143-3p, hinting a novel
      regulatory mechanism and potential therapeutic target in cervical cancer.

PMID- 29336660
TI  - Current Practice Patterns Surrounding Fertility Concerns in Stage I Seminoma
      Patients: Survey of United States Radiation Oncologists.
AB  - PURPOSE: Patients with testicular seminoma may face fertility issues because of
      their underlying disease as well as treatments they undergo. The current patterns
      of practice among U.S. radiation oncologists aimed at assessing and preserving
      fertility in patients with Stage I seminoma are unknown. METHODS: We surveyed
      practicing U.S. radiation oncologists via an Institutional Review Board-approved
      online questionnaire. Respondents' characteristics and perceived patient
      infertility rates were analyzed for association with treatment recommendations.
      RESULTS: We received 353 responses, of whom one quarter (23%) consider themselves
      experts. A vast majority (84%) recommend observation as a default strategy. Fifty
      two percent routinely advise fertility assessment for patients before observation
      or chemotherapy, and 74% routinely do so before adjuvant radiation therapy (RT).
      Forty-one percent and 43% believe that 10% and 30% of patients are infertile
      following orchiectomy, respectively. Thirty-seven percent and 22% believe
      infertility rates following para-aortic RT to be 30% and 50%, respectively.
      Eighty percent routinely use clamshell scrotal shielding. Responders with higher
      perceived infertility rates are more likely to recommend fertility
      assessment/sperm banking (Fisher's exact p < 0.0001). Responders who routinely
      advised fertility assessment were more likely to use clamshell shielding (Cochran
      Armitage trend test p = 0.0007). Clamshell use was positively correlated with
      higher perceived infertility rates following para-aortic RT (Spearman's
      correlation coefficient = 0.006). CONCLUSIONS: Despite a clear knowledge of
      fertility issues in men diagnosed with seminoma, there is no universal adoption
      of fertility assessment among U.S. radiation oncologists.

PMID- 29336661
TI  - Cancer-Related Genetic Testing and Personalized Medicine for Adolescents: A
      Narrative Review of Impact and Understanding.
AB  - Genetic testing is becoming increasingly available for adolescents who are
      undergoing cancer treatment or at risk of cancer predisposition syndromes. With
      this narrative review, we aimed to synthesize the evidence on psychosocial
      outcomes and adolescents' understanding of genetic testing-thus far, an
      underresearched topic. Both psychological benefits and harms of predictive
      testing were reported in adolescents from high-risk families. Harms were mainly
      related to cancer-specific distress and increased worries. Findings on genetic
      understanding were sparse. Future studies should focus on psychosocial outcomes
      and adolescents' understanding undergoing genetic testing and enabling access to
      genetic counseling pre-testing and post-testing.

PMID- 29336663
TI  - Lactobacillus acidophilus Improves Intestinal Inflammation in an Acute Colitis
      Mouse Model by Regulation of Th17 and Treg Cell Balance and Fibrosis Development.
AB  - Disruption of the balance among the microbiota, epithelial cells, and resident
      immune cells in the intestine is involved in the pathogenesis of inflammatory
      bowel disease (IBD). Probiotics exert protective effects against IBD, and
      probiotic commensal Lactobacillus species are common inhabitants of the natural
      microbiota, especially in the gut. To investigate the effects of Lactobacillus
      acidophilus on the development of IBD, L. acidophilus was administered orally in
      mice with dextran sodium sulfate (DSS)-induced colitis. DSS-induced damage and
      the therapeutic effect of L. acidophilus were investigated. Treatment with L.
      acidophilus attenuated the severity of DSS-induced colitis. Specifically, it
      suppressed proinflammatory cytokines such as interleukin (IL)-6, tumor necrosis
      factor-alpha, IL-1beta, and IL-17 in the colon tissues, which are produced by T
      helper (Th) 17 cells. Moreover, in vitro L. acidophilus treatment directly
      induced T regulatory (Treg) cells and the production of IL-10, whereas the
      production of IL-17 was suppressed in splenocytes. In addition, we found that L.
      acidophilus treatment decreased the levels of alpha-smooth muscle actin, a marker
      of activated myofibroblasts, and type I collagen compared with control mice.
      These results suggest that L. acidophilus may be a novel treatment for IBD by
      modulating the balance between Th17 and Treg cells, as well as fibrosis
      development.

PMID- 29336662
TI  - Body mass index in HER2-negative metastatic breast cancer treated with first-line
      paclitaxel and bevacizumab.
AB  - The evidence emerged from the TOURANDOT trial encourages evaluating the role of
      anthropometric determinants on treatment outcomes in HER2-negative metastatic
      breast cancer patients treated with bevacizumab-including regimens. We thus
      analyzed data from a subgroup of these patients from a larger cohort previously
      assessed for treatment outcomes. Patients were included in the present analysis
      if body mass index values had been recorded at baseline. Clinical benefit rates,
      progression free survival and overall survival were assessed for the overall
      study population and subgroups defined upon molecular subtype. One hundred ninety
      six patients were included (N:196). Body mass index showed no impact on clinical
      benefit rates in the overall study sample and in the luminal cancer subset (p =
      0.12 and p = 0.79, respectively), but did so in the triple negative subgroup,
      with higher rates in patients with body mass index >=25 (p = 0.03). In the
      overall study sample, body mass index did no impact progression free or overall
      survival (p = 0.33 and p = 0.67, respectively). Conversely, in triple negative
      patients, progression free survival was significantly longer with body mass index
      >=25 (6 vs 14 months, p = 0.04). In this subset, overall survival was more
      favorable (25 vs 19 months, p = 0.02). The impact of the molecular subtype was
      confirmed in multivariate models including the length of progression free
      survival, and number of metastatic sites (p < 0.0001). Further studies are
      warranted to confirm our findings in more adequately sized, ad hoc, prospective
      studies.

PMID- 29336664
TI  - Grab and passive sampling applied to pesticide analysis in the Sao Lourenco river
      headwater in Campo Verde - MT, Brazil.
AB  - In this study, the quality of surface water in the headwaters of Sao Lourenco
      River in Mato Grosso, Brazil, was evaluated in relation to contamination by
      pesticides. For this purpose, samples were collected between December 2015 and
      June 2016 by grab sampling and by passive sampling using an integrative polar
      organic compound sampler installed in the field during four 14-day cycles between
      March and June 2016. The analyses were performed by gas chromatography (CG/MS)
      and by liquid chromatography (UPLC-MS/MS). The results showed the detection of
      two pesticides (atrazine and pyraclostrobin) of the five analyzed by passive
      sampling and eight active principles among the 20 analyzed (malathion, diuron,
      carbofuran, carbendazim, trifluralin, imidacloprid, metolachlor, and acetamiprid)
      by grab sampling. The detection of 10 pesticides, even almost a decade after the
      beginning of a recovery process of the ciliary forest, confirms the headwaters'
      vulnerability to these contaminants and passive sampling proved to be an
      important tool in capturing small concentrations of pesticides constituting an
      interesting complement to grab sampling.

PMID- 29336665
TI  - Pesticide exposure and health conditions among orange growers in Southern Brazil.
AB  - This study aimed to evaluate the exposure to pesticides through the biomarkers
      analysis, as well as life habits and use of Personal Protective Equipment (PPE)
      in a group of farmers who grow citrus in the Vale do Cai region, in Rio Grande do
      Sul, southern Brazil. The study population consisted of 73 volunteer farmers, 45
      males and 28 females, aged between 13 and 69 years old. The control group
      consisted of 30 individuals who were not exposed to pesticides. Measures of urea,
      creatinine, aspartate aminotransferase (AST), alanine aminotransferase (ALT),
      gamma-glutamyltransferase (GGT), plasma cholinesterase (BChE) activity, and
      hematological parameters were analyzed. The study population also answered a
      structured questionnaire on life habits and health. The results showed that BChE
      activity was significantly lower in the exposed group than in the control group.
      AST, ALT, and creatinine were increased in the group of women exposed to
      pesticides when compared to the control group. GGT, urea, and hematological
      parameters did not show statistical differences for both male and female group.
      The most prevalent symptom reported by farmers after exposure to pesticides was
      headache. Furthermore, it was verified that the use of complete PPE is only made
      by 38% of the studied population.

PMID- 29336666
TI  - Educational Needs of Health Professionals Caring for Adolescents and Young Adults
      with Cancer.
AB  - BACKGROUND: Young people with cancer have distinct clinical and psychosocial
      needs during and after cancer treatment. However, as adolescent and young adult
      (AYA) cancer is rare, and only recently recognized as specialty, health
      professionals may not have the skills, competence, and confidence to meet the
      needs of the young patient with cancer. The aim of this study was to identify the
      learning needs of health professionals providing cancer care to adolescents and
      young adults before and following the introduction of a state-wide AYA cancer
      education program. METHODS: A survey of educational needs of health professionals
      was undertaken in 2013 at the commencement of the Queensland Youth Cancer
      Service. The survey was used to develop the education program of the service. The
      education program was delivered across the state in a variety of formats,
      covering a range of topics throughout 2013-2016. The second survey was completed
      in 2017. Results were compared to identify if educational needs or the self-rated
      confidence of health professionals in regard to AYA cancer care had changed over
      time. RESULTS: One hundred twenty-two participants completed the first survey and
      73 completed the second. The most prominent educational needs in 2013 were
      palliative care and biomedical topics such as understanding AYA growth and
      development as well as specific AYA cancers and treatment. The second survey
      identified that palliative care education remained important; however, there was
      a shift toward health professionals request for more psychosocial and practical
      education on topics including fertility, sexuality, and managing late effects.
      CONCLUSION: To provide high-quality healthcare to AYAs with cancer, health
      professionals require ongoing opportunities for education and training.

PMID- 29336667
TI  - Influence of long-term consumption of bitter apricot seeds on risk factors for
      cardiovascular diseases.
AB  - The present study was designed to reveal whether long-term consumption of bitter
      apricot seeds causes changes in lipid profile and other risk factors for
      cardiovascular diseases. The study group consisted of 12 healthy adult volunteers
      (5 females and 7 males). The average age of women was 41.60 +/- 11.28 years and
      the average age of men was 36.71 +/- 13.70 years. Volunteers consumed 60 mg kg-1
      of body weight of bitter apricot seeds divided into 8-12 doses daily for 12
      weeks. Volunteers were recruited from the general population of Slovak Republic.
      After 12 weeks, mean body weight of the participants increased from 77.34 to
      78.22 kg (P > 0.05). The average total cholesterol levels decreased from 4.86
      mmol L-1 at the beginning of the study to 4.44 mmol L-1 at the end of the study
      (P < 0.05). We did not observe any significant increase in high-density
      cholesterol (from 1.55 to 1.60 mmol L-1). The average low-density cholesterol
      levels decreased from 2.93 mmol L-1 at the beginning of the study to 2.31 mmol L
      1 at the end of the study (P < 0.001). Concentration of triglycerides increased
      significantly over the 12-week intervention period from 0.84 to 1.17 mmol L-1.
      After the intervention, the high-sensitivity C-reactive protein level decreased
      from 1.92 to 1.23 mg L-1, but results were non-significant (P > 0.05). Creatine
      kinase serum levels increased from 2.31 to 2.77 mg L-1 (P > 0.05) over the 12
      week intervention period. The results suggest that regular intake of bitter
      apricot seeds may be considered potentially useful for prevention of
      cardiovascular diseases.

PMID- 29336668
TI  - Safety and biodistribution of sulfated archaeal glycolipid archaeosomes as
      vaccine adjuvants.
AB  - Archaeosomes are liposomes comprised of ether lipids derived from various
      archaea. Unlike conventional ester-linked liposomes, archaeosomes exhibit high pH
      and thermal stability. As adjuvants, archaeosomes can induce robust, long-lasting
      humoral and cell-mediated immune responses and enhance protection in murine
      models of infectious disease and cancer. Archaeosomes constituted with total
      polar lipids (TPL) of various archaea are relatively complex, comprising >10
      different lipid compounds. Archaeosomes can be constituted with semi-synthetic
      glycerolipids built on ether-linked isoprenoid phytanyl cores with varied
      synthetic glycol- and amino-head groups. However, such semi-synthetic
      archaeosomes involve many synthetic steps to arrive at the final desired
      glycolipid composition. We have developed a novel archaeosome formulation
      comprising a sulfated saccharide group covalently linked to the free sn-1
      hydroxyl backbone of an archaeal core lipid (sulfated S-lactosylarchaeol, SLA)
      mixed with uncharged glycolipid (lactosylarchaeol, LA). This new class of
      adjuvants can be easily synthesized and retains strong immunostimulatory activity
      for induction of cell-mediated immunity following systemic immunization. Herein,
      we demonstrate the safety of SLA/LA archaeosomes following intramuscular
      injection to mice and evaluate the immunogenicity, in vivo distribution and
      cellular uptake of antigen (ovalbumin) encapsulated into SLA/LA archaeosomes.
      Overall, we have found that semi-synthetic sulfated glycolipid archaeosomes are a
      safe and effective novel class of adjuvants capable of inducing strong antigen
      specific immune responses in mice and protection against subsequent B16 melanoma
      tumor challenge. A key step in their mechanism of action appears to be the
      recruitment of immune cells to the injection site and the subsequent trafficking
      of antigen to local draining lymph nodes.

PMID- 29336669
TI  - First-line treatment of apatinib in elderly patient of advanced gastric
      carcinoma: A case report of NGS-driven targeted therapy.
AB  - Gastric carcinoma (GC) is a common gastrointestinal malignancy with high
      incidence and mortality worldwide, and most patients are diagnosed in the late
      stages of disease. Palliative chemotherapy provides a survival benefit for
      patients with inoperable advanced GC. However, elderly patients who are unable to
      tolerate chemotherapy had worse prognosis due to lack of effective treatment.
      Herein we reported a Chinese elderly GC patient using next generation sequencing
      (NGS)-based tumor DNA analysis. Valuable gene variants of vascular endothelial
      growth factor (VEGF) A gene amplification were detected. Additionally, a novel
      NOTCH1-BPHL fusion has been identified. He received antiangiogenic drug apatinib
      and showed both good clinical and radiographic response, but eventually died of
      non-cancer related cause, with progression free survival time (PFS) and overall
      survival time (OS) up to 9.53 months. This was the first GC case with apatinib
      usage as first-line treatment under the guidance of NGS gene profiling.

PMID- 29336670
TI  - Does Drug Use Inhibit Crime Deceleration or Does Crime Inhibit Drug Use
      Deceleration? A Test of the Reciprocal Risk Postulate of the Worst of Both Worlds
      Hypothesis.
AB  - BACKGROUND: Prior research has shown that ongoing drug use inhibits the commonly
      reported maturing out of crime process and that ongoing crime inhibits the
      commonly reported maturing out of drug use process. OBJECTIVES: To test the
      predictive efficacy of drug use for crime deceleration and of crime for drug
      deceleration using a prospective analysis of data on a group of 524 male
      California Youth Authority parolees to see if both effects exist simultaneously.
      METHOD: A two-equation regression analysis of Year 3 arrests and illicit drug use
      was performed, controlling for age, race, marital status, employment status, and
      number of months free in the community. RESULTS: It was determined that illicit
      drug use at Year 2 predicted an increase in arrests between the first and third
      years of the analysis and arrests at Year 2 predicted an increase in illicit drug
      use over this same time period. Alcohol use, on the other hand, failed to predict
      a change in arrests and arrests failed to predict a change in alcohol use.
      CONCLUSIONS: The results of this study suggest that illicit drug use may inhibit
      the natural maturing out of crime process observed in emerging adults whereas
      involvement in crime may inhibit the natural maturing out of illicit drug use
      process. These findings not only support the reciprocal risk postulate from the
      Worst of Both Worlds hypothesis but also have implications for risk prediction,
      risk management, and treatment.

PMID- 29336671
TI  - The Indirect Effect of Ethnic Identity on Marijuana Use Through School
      Engagement: An African American High School Sample.
AB  - BACKGROUND: African American marijuana use is associated with many negative
      social, emotional, and health-related consequences. Of significance, over recent
      years this population has shown an increase in use. In the literature, ethnic
      identity and school engagement are prominent protective factors against substance
      use. OBJECTIVE: This study will examine how these protective factors are related,
      specifically whether ethnic identity mitigates risk through school engagement to
      reduce marijuana use. METHOD: A path analysis was conducted with 437 African
      American high school students (41% male) from Midwestern schools to examine the
      role of school engagement in the relationship between ethnic identity and
      marijuana use. RESULTS: The results revealed that students high in ethnic
      identity have higher school engagement, which lessens their frequency of
      marijuana use. Therefore, ethnic identity reduces marijuana use by increasing
      student's school engagement. Conclusions/Importance: The results offer a clearer
      picture of how ethnic identity and school engagement protect against marijuana
      use. The results also present insight into how to protect students who are low in
      ethnic identity.

PMID- 29336672
TI  - Internal Cs+ inhibits root elongation in rice.
AB  - The root system anchors the plant to the soil and contributes to plant autotrophy
      by taking up nutrients and water. In relation with this nutritional function,
      root development is largely impacted by availability of nutrients and water. Due
      to human activity, plants, in particular crops, can also be exposed to pollutants
      which can be absorbed and incorporated into the food chain. Cesium in soils is
      present at non-toxic concentrations for the plant (micromolar or less), even in
      soils highly polluted with radioactive cesium due to nuclear accidents. Here, we
      report on the morphological response of rice roots to Cs+ at micromolar
      concentrations. It is shown that Cs+ reduces root elongation without affecting
      root dry weight. Noteworthy, inactivation of the Cs+-permeable K+ transporter
      OsHAK1 prevents such effect of Cs+, suggesting that internal Cs+ triggers the
      modification of the root system.

PMID- 29336673
TI  - A practical synthesis of xylo- and arabinofuranoside precursors by
      diastereoselective reduction using Corey-Bakshi-Shibata catalyst.
AB  - The Corey-Bakshi-Shibata (CBS) catalyst provides an efficient mechanism to reduce
      ketones and achieve desired enantiopure alcohols. Herein, the diastereoselective
      reduction of C-2' and C-3'-keto ribofuranoside derivatives to the corresponding
      arabino- and xylofuranosides in greater than 95% diastereomeric excess is
      reported. The stereo-directed substitution with an azido group as well as the
      synthesis of prodrugs cytarabine and vidarabine are also described. The reported
      strategy offers superior diastereoselectivity, shorter reaction times, and
      obviates cooling required with comparable protocols involving achiral reductants.

PMID- 29336674
TI  - A facile synthesis of novel pyrazolopyrimidine thioglycosides as purine
      thioglycoside analogues.
AB  - The easy, convenient and high yielding preparation of new thioglycosides
      incorporating mercaptopyrazolo[1,5-a]pyrimidine moieties from readily accessible
      starting materials has been reported. The main step of this protocol is the
      formation of 7-mercaptopyrazolo[1,5-a]pyrimidine-6-carbonitrile derivatives 4a-d
      by condensation of sodium 2-cyano-3-ethoxy-3-oxoprop-1-ene-1,1-bis(thiolate) 1
      with 4-(aryldiazenyl)-1H-pyrazole-3,5-diamines 3a-d to form target compounds 4a
      d, which coupled with tetra-O-acetyl-alpha-D-glycopyranosyl bromides 5a,b in the
      presence of basic medium to provide the corresponding product purine
      thioglycoside analogs 6a-h. Ammonolysis of the latter compounds 6a-d at ambient
      temperature for 10 minutes, led to the free glycoside derivatives 7a-h, which
      were obtained in approximately quantitative yields. Their structures were created
      based on the spectroscopic and elemental data.

PMID- 29336675
TI  - Synthesis and cytotoxic activity of novel acyclic nucleoside analogues with
      functionality in click chemistry.
AB  - We describe synthesis of novel acyclic nucleoside analogues which are building
      blocks for CuAAC reaction and their activity against two types of human cancer
      cell lines (HeLa, KB). Three of chosen compounds show promising cytotoxic
      activity. Synthesis pathway starting from simple and easily accessible substrates
      employing DMT or TBDPS protective groups is described. Adenosine and thymidine
      analogues containing alkyne moiety and adenosine analogue containing azido group
      were synthesized. The obtained units showed ability of forming triazole motif
      under the CuAAC reaction conditions.

PMID- 29336676
TI  - Vasopressors in Sepsis.
AB  - BACKGROUND: Sepsis accounts for 10% of intensive care unit admissions and
      significant healthcare costs. Although the mortality rate from sepsis has been
      decreasing with better critical care, early identification of septic patients,
      and prompt interventions, the mortality rate remains 20%-30%. METHOD: Review of
      the English-language literature. RESULTS: Norepinephrine is the first-line
      vasopressor in shock and is associated with a lower mortality rate as well as
      fewer adverse effects. Dopamine has similar actions but is associated with
      significantly more tachydysrhythmias and should be reserved for patients with
      bradycardia. Epinephrine and vasopressin are appropriate second-line vasopressors
      and may enable use of lower doses of norepinephrine while improving hemodynamics.
      Inotropes may be added in patients with cardiac dysfunction. CONCLUSION:
      Appropriate treatment of sepsis includes prompt identification, early
      antimicrobial drug therapy, appropriate fluid resuscitation, and initiation of
      vasopressors in the presence of continued septic shock. Further research needs to
      be done to better understand the ideal timing of the addition of a second agent
      and the optimal combinations of vasopressors for individual patients.

PMID- 29336677
TI  - Molecular Screening Versus Phenotypic Susceptibility Testing of Multidrug
      Resistant Mycobacterium tuberculosis Isolates for Streptomycin and Ethambutol.
AB  - Proper management of multidrug-resistant tuberculosis (MDR-TB) requires accurate
      drug susceptibility testing (DST) of Mycobacterium tuberculosis isolates to other
      (ethambutol [EMB], pyrazinamide, and streptomycin [SM]) first-line drugs. This
      study compared the performance of Mycobacterium Growth Indicator Tube (MGIT) 960
      system for DST of MDR-TB isolates with polymerase chain reaction (PCR) sequencing
      of embB, rpsL, and rrs genes for detecting resistance to EMB and SM. MDR-TB
      strains (n = 60) and 25 pansusceptible M. tuberculosis isolates collected during
      2011-2016 were tested. Phenotypic DST was performed by MGIT 960 system by using
      SIRE drug kit. EMB and SM resistance-conferring mutations in embB and rpsL+rrs
      genes, respectively, were detected by PCR sequencing. No mutations were detected
      in pansusceptible isolates. Among 60 MDR-TB strains, 35 of 40 SM-resistant and
      none of 20 SM-susceptible isolates contained rpsL and/or rrs mutations (kappa =
      0.82, very good agreement). However, all 18 EMB-resistant MDR-TB strains and 33
      of 42 EMB-susceptible MDR-TB strains contained an embB mutation (kappa = 0.14,
      poor agreement). Thus, 40 of 60 (67%) and 35 of 60 (58%) isolates were resistant
      to SM (p = 0.451), while 18 of 60 (30%) and 51 of 60 (85%) isolates were
      resistant to EMB (p = 0.000) by MGIT 960 system and PCR sequencing, respectively.
      MGIT 960 system showed acceptable performance for DST for SM; however, it
      performed poorly for EMB as many MDR-TB strains with embB mutations, which confer
      low-level resistance to EMB, were detected as EMB susceptible. Molecular
      screening for resistance-conferring mutations in embB gene is thus superior to
      MGIT 960 system when accurate EMB susceptibility results are needed for proper
      management of MDR-TB patients.

PMID- 29336678
TI  - Phylogeny and diversity of the morphologically similar polypore genera
      Rigidoporus, Physisporinus, Oxyporus, and Leucophellinus.
AB  - Rigidoporus and its morphologically similar genera Physisporinus, Oxyporus, and
      Leucophellinus, which include some forest pathogens and medicinal species, are
      very important groups of wood-decaying fungi. Species of these genera have not
      only ecological functions, but also economic importance. Phylogenetic and
      taxonomic studies on taxa in these genera were carried out. Inferred from
      phylogenies based on DNA sequences of the nuc rDNA ITS1-5.8S-ITS2 (internal
      transcribed spacer [ITS]) and D1-D2 domains of nuc 28S rDNA, 36 species sampled
      that traditionally belong to Physisporinus, Rigidoporus, Leucophellinus, and
      Oxyporus are nested mostly in eight lineages. Of these lineages, five (including
      four genera of Physisporinus, Emmia, Flaviporus, and Flavodon and one taxon "R.
      hypobrunneus") belong to Polyporales and three (including the genera Rigidoporus,
      Bridgeoporus, and Leucophellinus) belong to Hymenochaetales. Rigidoporus and
      Oxyporus are merged because the type species of both genera are nested in a
      single lineage within Hymenochaetales. Some taxon previously placed in Ceriporia
      and Oxyporus are transferred to Emmia and Flavodon, respectively, on the basis of
      current phylogeny. Utilizing a combination of the morphological and phylogenetic
      evidence, 16 new combinations in Bridgeoporus, Emmia, Flaviporus, Flavodon,
      Rigidoporus, and Physisporinus are proposed. Five new species, Physisporinus
      crataegi, P. lavendulus, P. subcrocatus, P. tibeticus, and Rigidoporus
      submicroporus, are recognized from China. Illustrated descriptions of these novel
      species are provided. Three taxa are treated at the generic level of
      Physisporinus because of limited samples.

PMID- 29336679
TI  - Arcobacter butzleri Ciprofloxacin Resistance: Point Mutations in DNA Gyrase A and
      Role on Fitness Cost.
AB  - Arcobacter butzleri is a widely distributed emerging pathogen resistant to
      various classes of antimicrobial agents, namely fluoroquinolones. A. butzleri
      resistance to fluoroquinolones is conferred by point mutations at the antibiotic
      target. The aim of this study was to evaluate mutations at gyrA associated with
      ciprofloxacin resistance and evaluate whether acquisition of resistance impacts
      on fitness and stress tolerance of A. butzleri. A. butzleri ciprofloxacin mutants
      were generated by laboratory induction. Identification of mutations associated
      with ciprofloxacin resistance was performed by gyrA sequencing. Growth kinetics,
      cost of fitness, biofilm formation ability, and stress tolerance were assessed.
      Two amino acid substitutions in the quinolone resistance-determining region of
      GyrA were identified in the mutant strains, one previously described (Thr-85-Ile)
      and a new substitution (Asp-89-Tyr). No differences in growth kinetics were
      recorded between parental and mutant strains; however, fitness cost was variable,
      according to the genetic background of the strains, and independently of
      ciprofloxacin resistance. Overall, the ciprofloxacin resistance development did
      not significantly affect stress tolerance, motility, or biofilm-forming ability.
      In conclusion, acquisition of ciprofloxacin resistance in A. butzleri is
      associated with mutations in gyrA and is likely well compensated, with cost of
      fitness reflecting the diversity in genetic background of this bacterium.

PMID- 29336680
TI  - Relating soil geochemical properties to arsenic bioaccessibility through
      hierarchical modeling.
AB  - Interest in improved understanding of relationships among soil properties and
      arsenic (As) bioaccessibility has motivated the use of regression models for As
      bioaccessibility prediction. However, limits in the numbers and types of soils
      included in previous studies restrict the usefulness of these models beyond the
      range of soil conditions evaluated, as evidenced by reduced predictive
      performance when applied to new data. In response, hierarchical models that
      consider variability in relationships among soil properties and As
      bioaccessibility across geographic locations and contaminant sources were
      developed to predict As bioaccessibility in 139 soils on both a mass fraction
      (mg/kg) and % basis. The hierarchical approach improved the estimation of As
      bioaccessibility in studied soils. In addition, the number of soil elements
      identified as statistically significant explanatory variables increased when
      compared to previous investigations. Specifically, total soil Fe, P, Ca, Co, and
      V were significant explanatory variables in both models, while total As, Cd, Cu,
      Ni, and Zn were also significant in the mass fraction model and Mg was
      significant in the % model. This developed hierarchical approach provides a novel
      tool to (1) explore relationships between soil properties and As bioaccessibility
      across a broad range of soil types and As contaminant sources encountered in the
      environment and (2) identify areas of future mechanistic research to better
      understand the complexity of interactions between soil properties and As
      bioaccessibility.

PMID- 29336681
TI  - Exposure to firework chemicals from production factories in pregnant women and
      risk of preterm birth occurrence in Liuyang, China.
AB  - In the production of fireworks, various pollutants including particles of metals
      and organic compounds are released into the environment. Although the adverse
      effects of these air pollutants are known, the impact on pregnant women residing
      in this area remains to be determined. The aim of this study was to examine the
      association between maternal exposure to fireworks production chemicals and
      frequency of preterm birth in Liuyang, China. Maternal exposure to fireworks
      production was estimated at the residential district level and assessed using
      factory density, which was defined as the number of fireworks factories per 1000
      residents in each district. The association of maternal exposure to particulates
      released from fireworks production plants with frequency of preterm birth was
      determined using data obtained from a cohort study conducted in Liuyang, China.
      Data were analyzed utilizing linear regression and logistic regression. There was
      no significant association between factory density and spontaneous preterm or
      medically induced preterm birth. Unexpectedly, pregnant women residing in areas
      with higher density of fireworks factories were at a reduced risk of preterm
      premature rupture of membranes (PPROM). Data demonstrated that residential
      density of fireworks factories appeared to be negatively correlated with preterm
      birth rate as evidenced by PPROM. At present, it is difficult to reconcile the
      inverse relationship between firework chemical exposure and frequency of preterm
      births as ambient particulate inhalation is known to adversely affect preterm
      birth occurrence.

PMID- 29336682
TI  - Preliminary phylogeny of Coemansia (Kickxellales), with descriptions of four new
      species from Taiwan.
AB  - Four new species of Coemansia from Taiwan are described. Three produce spirally
      twisted sporangiophores, and these new taxa increase the number of species in the
      Coemansia spiralis complex from three to six. Each new taxon is morphologically
      unique. Coemansia biformis, sp. nov., has two different asexual reproductive
      types on the same thallus; one is straight and the other has a spiral fertile
      region. Coemansia helicoidea, sp. nov., has stoloniferous sporangiophores with a
      helicoid fertile region. Coemansia pennisetoides, sp. nov., has a sporangiophore
      with a fertile region that resembles the inflorescence of the plant genus
      Pennisetum. Coemansia umbellata, sp. nov., has an umbellate sporangiophore
      branching pattern and a spirally twisted fertile region on the lowest branches. A
      dichotomous key was provided to identify the 23 accepted Coemansia species.
      Phylogenetic analysis based on a combined data set of D1-D2 domains of nuc 28S
      ribosomal RNA (rDNA) and partial nuc 18S rDNA identifies several independent
      evolutionary lineages within Coemansia and suggests that Spirodactylon aureum and
      Kickxella alabastrina may be nested within the genus Coemansia. Sequences of nuc
      rDNA ITS1-5.8S-ITS2 (internal transcribed spacer [ITS] barcode) are also used to
      support the description of these new species of Coemansia.

PMID- 29336683
TI  - Adsorption of 2,4-dichlorophenoxyacetic acid and 4-chloro-2-metylphenoxyacetic
      acid onto activated carbons derived from various lignocellulosic materials.
AB  - Adsorption of 2,4-dichlorophenoxyacetic acid (2,4-D) and 4-chloro-2
      metylphenoxyacetic acid (MCPA) from aqueous solution onto activated carbons
      derived from various lignocellulosic materials including willow, miscanthus,
      flax, and hemp shives was investigated. The adsorption kinetic data were analyzed
      using two kinetic models: the pseudo-first order and pseudo-second order
      equations. The adsorption kinetics of both herbicides was better represented by
      the pseudo-second order model. The adsorption isotherms of 2,4-D and MCPA on the
      activated carbons were analyzed using the Freundlich and Langmuir isotherm
      models. The equilibrium data followed the Langmuir isotherm. The effect of pH on
      the adsorption was also studied. The results showed that the activated carbons
      prepared from the lignocellulosic materials are efficient adsorbents for the
      removal of 2,4-D and MCPA from aqueous solutions.

PMID- 29336684
TI  - A Systematic Search and Review of Adult-Targeted Overweight and Obesity
      Prevention Mass Media Campaigns and Their Evaluation: 2000-2017.
AB  - Mass media campaigns are a commonly used strategy in public health. However, no
      review has assessed whether the design and evaluation of overweight and obesity
      campaigns meets best practice recommendations. This study aimed to fill this gap.
      We systematically searched five databases for peer-reviewed articles describing
      adult-targeted obesity mass media campaigns published between 2000 and 2017,
      complemented by reference list searches and contact with authors and agencies
      responsible for the campaigns. We extracted data on campaign design,
      implementation, and evaluation from eligible publications and conducted a
      qualitative review of 29 publications reporting on 14 campaigns. We found a need
      for formative research with target audiences to ensure campaigns focus on the
      most salient issues. Further, we noted that most campaigns targeted individual
      behaviors, despite calls for campaigns to also focus upstream and to address
      social determinants of obesity. Television was the dominant communication channel
      but, with the rapid advance of digital media, evaluation of other channels, such
      as social media, is increasingly important. Finally, although evaluation methods
      varied in quality, the evidence suggests that campaigns can have an impact on
      intermediate outcomes, such as knowledge and attitudes. However, evidence is
      still limited as to whether campaigns can influence behavior change.

PMID- 29336685
TI  - Seroprevalence of Q Fever Among the Indigenous People (Orang Asli) of Peninsular
      Malaysia.
AB  - Q fever is a disease caused by Coxiella burnetii. It is a disease of public
      health concern in many parts of the world. In this study, we described the
      seroprevalence of Q fever among selected populations of Orang Asli (OA),
      indigenous people, many of whom live within the forest fringe areas of Peninsular
      Malaysia. Serum samples were obtained from 887 OA participants from selected
      villages. Samples were analyzed for the presence of IgG antibodies reactive
      against C. burnetii by enzyme-linked immunosorbent assay. Statistical methods
      were used to identify possible associations between seropositivity for C.
      burnetii and a number of demographic variables obtained from the questionnaires.
      In total, 9.6% (n = 85/887) of the serum samples were reactive to C. burnetii.
      Statistical results suggest that elderly male OA residing in OA village, Bukit
      Payung, were most likely to be tested seropositive for C. burnetii. This study
      suggests that OA are at a significant risk of contracting C. burnetii infection,
      and both demographic and geographic factors are important contributors to this
      risk. Further prospective studies are needed to establish the true burden of C.
      burnetii infection within the indigenous population as well as within Peninsular
      Malaysia as a whole.

PMID- 29336686
TI  - Phylogeny and taxonomy of Favolus (Basidiomycota).
AB  - Favolus is a natural genus that is closely related to Polyporus. A taxonomic
      study of Favolus was carried out based on morphological characteristics and
      phylogenetic analysis of the internal transcribed spacer (ITS) region (ITS1-5.8S
      ITS2 = ITS) and 18S and 28S genes of the nuc rDNA, translation elongation factor
      1-alpha gene (TEF1-alpha), the mt 16S rDNA gene (mt rrnS), beta-tubulin gene
      (TBB1), and the RNA polymerase II largest subunit (RPB1) and second largest
      subunit (RPB2) genes. Fourteen specimens collected from subtropical to tropical
      regions in China were shown to be different from existing Favolus species. They
      are described and illustrated here as four new species, namely, Favolus niveus,
      F. septatus, F. pseudoemerici, and F. subtropicus.

PMID- 29336687
TI  - Reasons why undergraduate women comply with unwanted, non-coercive sexual
      advances: A serial indirect effect model integrating sexual script theory and
      sexual self-control perspectives.
AB  - This study explored the predictors of young women's compliance with unwanted
      sexual activities, integrating the social with the cognitive and behavioral
      correlates of sexual compliance. In total, 222 young heterosexual women completed
      measures examining the Sexual Self-Control model, including reasons for
      consenting, sexual resourcefulness, and compliance with unwanted sex, as well as
      gender role measures pertaining to sexual script theory, including the sexual
      double standard, gender role stress, and virginity scripts. An exploratory
      analysis of serial indirect effects demonstrated that women scoring lower in
      sexual resourcefulness endorsed higher female gender role stress, which in turn
      was associated with higher endorsement of reasons for consent, translating into
      more frequent compliance with unwanted sexual activities. The relationship
      between one's ability to refuse and their decision to refuse appears quite
      complex. Understanding one's decision requires consideration of the social
      aspects of gender role endorsement.

PMID- 29336688
TI  - Beliefs about Memory as a Mediator of Relations between Metacognitive Beliefs and
      Actual Memory Performance.
AB  - The goal of the present study was to investigate relationships between personal
      beliefs about memory, metacognitive beliefs, and actual memory performance. One
      hundred thirty-seven participants' (aged 20 to 60 years) metacognitive beliefs
      were measured using the Metacognition Questionnaire (MCQ-30), memory beliefs were
      measured using the Personal Beliefs about Memory Instrument (PBMI), and an
      episodic memory task was used to measure actual memory performance, memory
      predictions, and postdictions. Younger adults had lower scores on the positive
      beliefs subfactor of the MCQ-30, higher scores on retrospective change and
      control subfactors of the PBMI, and outperformed middle-aged adults on recall and
      recall postdiction. Path analysis showed that individuals' beliefs about memory
      mediate the relationship between metacognitive beliefs and actual memory
      performance. Specifically, low lack of confidence (or less worry) in one's own
      memory and attentional capabilities was related to higher memory performance and
      positive personal beliefs regarding specific memory ability mediated
      relationship.

PMID- 29336689
TI  - A Molecular Survey of Tick-Borne Pathogens from Ticks Collected in Central
      Queensland, Australia.
AB  - Central Queensland (CQ) is a large and isolated, low population density, remote
      tropical region of Australia with a varied environment. The region has a diverse
      fauna and several species of ticks that feed upon that fauna. This study examined
      518 individual ticks: 177 Rhipicephalus sanguineus (brown dog tick), 123
      Haemaphysalis bancrofti (wallaby tick), 102 Rhipicephalus australis (Australian
      cattle tick), 47 Amblyomma triguttatum (ornate kangaroo tick), 57 Ixodes
      holocyclus (paralysis tick), 9 Bothriocroton tachyglossi (CQ short-beaked echidna
      tick), and 3 Ornithodoros capensis (seabird soft tick). Tick midguts were pooled
      by common host or environment and screened for four genera of tick-borne zoonoses
      by PCR and sequencing. The study examined a total of 157 midgut pools of which 3
      contained DNA of Coxiella burnetii, 13 Rickettsia gravesii, 1 Rickettsia felis,
      and 4 other Rickettsia spp. No Borrelia spp. or Babesia spp. DNA were recovered.

PMID- 29336690
TI  - Advanced glaucoma at presentation is associated with poor follow-up among
      glaucoma patients attending a tertiary eye facility in Southern Nigeria.
AB  - PURPOSE: Globally, particularly in Africa, poor compliance with medication is a
      major problem in glaucoma management but little is known about follow-up rates
      among African glaucoma patients. The aim of this study was to determine rates of
      follow-up among glaucoma patients attending a tertiary hospital in southern
      Nigeria and investigate predictors of poor follow-up. METHODS: Data were
      extracted from medical records of new glaucoma patients who attended the hospital
      between June 2011 and May 2013. Socio-demographic and clinical parameters (visual
      acuity; stage of glaucoma) recorded at diagnosis were extracted using a pre
      tested form. Follow-up was defined as good if they had attended within 9 months
      of the study date, inadequate when the last follow-up was more than 9 months and
      failed if they did not attend any follow-up or the most recent visit was more
      than 14 months from the study date. Univariate and multivariable analyses were
      undertaken to explore predictors of poor follow-up (inadequate plus failed).
      RESULTS: Three hundred forty-eight patients were recruited, 54% were male and the
      mean age was 52.7 (range 16-88) years. Follow-up was as follows: good 28.4%,
      inadequate 46.6%, failed 25%. Overall, 71.6% had poor follow-up. Independent
      predictors of poor follow-up were poorer visual acuity (OR 3.85, 95% confidence
      interval (CI) 1.25-11.80 for visual impairment; OR 4.11, 95% CI 1.32-12.81 for
      blind) and end-stage glaucoma (OR 3.55 (1.31-9.62), p = 0.01). CONCLUSION:
      Enhanced counselling of patients with moderate to advanced glaucoma and visual
      impairment is required to improve follow-up and hence glaucoma management.

PMID- 29336691
TI  - The evaluation of Cr-curcumin-DNA complexation by experimental and theoretical
      approaches.
AB  - Chromium(III) chloride mediates DNA-DNA cross-linking. Some chromium complexes
      promote programmed cell death in specific ligand environment through binding to
      DNA. One strategy that can be supposed for reduction of Cr3+ binding affinity to
      DNA is using curcumin as a chelator. In the current study, the
      [Cr(Curcumin)(EtOH)2](NO3)2 (CCC) was synthesized and characterized by UV/Vis, FT
      IR, CHN and spectrophotometric titration techniques. The mole ratio plot revealed
      a 1:1 complex between Cr3+ and curcumin in solution. Binding interaction of this
      complex with calf thymus-DNA (CT-DNA) was investigated using UV/Vis, circular
      dichroism (CD), FT-IR and cyclic voltammetry. The intrinsic binding constants of
      CCC with DNA, measured by UV/Vis and cyclic voltammetry, were 1.60 * 105 and 1.13
      * 105, respectively. The thermodynamic studies showed that the reaction is
      enthalpy and entropy favoured. CD analysis revealed that only Lambda-CCC
      interacts with DNA and Delta-CCC form has no tendency towards DNA. Based on FT-IR
      studies, it was understood that CCC interacts with DNA via minor groove binding.
      The docking simulation was carried out for finding the binding mode of CCC to
      DNA, too. All of data demonstrated that the curcumin significantly reduced the
      affinity of Cr3+ to the DNA and the form of Delta-CCC has no interaction with
      DNA.

PMID- 29336692
TI  - The First Serological Study of Q Fever in Humans in Lebanon.
AB  - OBJECTIVE: The aim of this study was to estimate, for the first time, the human
      seroprevalence of Q fever in Lebanon, by assessing the presence of antibodies
      against the causative agent, Coxiella burnetii. A total number of 421 serum
      samples (226 females and 196 males) were collected in February 2015 from
      hospitals and laboratories dispersed in five Lebanese provinces: Akkar, Bekaa,
      Mount Lebanon, Nabatieh, and South Lebanon. METHODS: Serial testing approach was
      used. Samples were first screened for IgG phase II antibodies against C. burnetii
      by Enzyme Linked Immunosorbent Assay (ELISA) Kit. Then, both positive and
      inconclusive sera were reexamined by immunofluorescence assay (IFA) test with the
      aims to confirm and specify the infection status (past or probably acute
      infection) by detecting IgG (I/II) and IgM (I/II) in human sera. RESULTS:
      Screening of 421 samples was estimated to be 38.70% (95% CI 34-43.3) positive
      samples, 5.90% (95% CI 3.7-8.2) suspect samples (as doubtful results), and 55.40%
      (95% CI 50.7-60.1) negative samples. Furthermore, all positive and suspect
      samples by ELISA test were retested by immunofluorescence assay test (IFAT), and
      the prevalence of positive sample was 37% and the infection case was recorded:
      23.75% (95% CI 19.7-27.8) samples resulted from past infection, 1.9% (95% CI 0.6
      3.2) probably acute infection characterized by several dominance clinical
      symptoms as: fever, cough, headache, difficulty breathing, and atypical
      pneumonia, and 0.23% (95% CI 0-0.7) inconclusive sample accompanied by different
      symptoms as bone metastasis and lung cancer. CONCLUSION: The study records the
      exposition of 37% of 421 patients to C. burnetii distributed in five Lebanese
      provinces with the highest seroprevalence in Bekaa and Akkar provinces and the
      lowest reported in Mount Lebanon. This difference may be due to the presence of
      high density of livestock production and of major agricultural areas in these two
      provinces.

PMID- 29336693
TI  - Self-Other Differentiation Scale: Dimensionality, IRT Parameterization, and
      Measurement Invariance.
AB  - The Self-Other Differentiation Scale (Olver, Aries, & Batgos, 1989 ) is a self
      report instrument assessing the experience of a separate sense of self from
      others. The authors aimed to examine its dimensionality, reliability, and
      measurement invariance across gender. It was completed by 348 participants (48%
      men) from 17 to 30 years old in Study 1, 348 participants (40% men) from 18 to 28
      years old in Study 2, and 1,068 participants (49% men) from 17 to 28 years old in
      Study 3. The results supported the hypothesis of just one factor underlying the
      scale; they also showed an appropriate internal consistency and a partial
      measurement invariance across gender. Results also showed evidence for a 10-item
      version of the scale. Globally, the Self-Other Differentiation Scale can be
      considered a good scale to assess individual's sense of differentiation of one's
      own sense of self from others.

PMID- 29336694
TI  - "It has changed my whole life": The systemic implications of chronic low back
      pain among older adults.
AB  - Chronic low back pain (CLBP) is the most common pain complaint among older
      adults. Despite its prevalence, very little research has qualitatively examined
      the diverse consequences of living with CLBP in later life. As part of a larger
      study aiming to understand the experience of CLBP among older adults, the
      objective of this manuscript is to understand how older adults experience CLBP
      and its impacts on the functioning of older adults. Guided by van Manen's
      phenomenological method, 23 semi-structured interviews with 21 pain clinic
      patients aged 66-83 were conducted. Through an iterative process assisted by
      NVivo 11 software, researchers used line-by-line thematic coding to identify main
      impacts of CLBP. Under the main theme "It has changed my whole life," results are
      reflected in six subthemes: (a) Pain damages sense of self; (b) trapped in a body
      that doesn't work anymore; (c) me, my partner, and my pain; (d) pain complicates
      family relationships; (e) painfully employed; and (f) feeling socially and
      recreationally repressed. This study improves our understanding of older pain
      clinic patients' experience of living with debilitating CLBP and offers direction
      for social work intervention in the context of multidisciplinary pain management.

PMID- 29336695
TI  - "Ghosts from the past": The re-emergence of internalized religious stigma
      following diagnosis of HIV among Northern Irish gay men.
AB  - This article explores how previous exposure to religious homonegativity features
      in the sense-making process following HIV diagnosis in a homogenous sample of six
      gay men living in Northern Ireland. Interpretive phenomenological analysis was
      used to identify two key overarching themes: Negotiating authenticity in unsafe
      space, which relates to the experience of negotiating same-sex attraction within
      religious environments, and Re-emergence of religious shame in diagnosis, which
      relates to the way in which the men made sense of diagnosis from the position of
      having been exposed to religious homonegativity earlier in their lives. Findings
      demonstrate how the men negotiated their sexual orientation within religious
      contexts and how a reconstruction of God was necessary to preserve an authentic
      sense of self. Despite reaching reconciliation, HIV was initially appraised
      within a retributive religious framework that served to temporarily reinforce
      previously learned shame-based models of understanding this aspect of the self.

PMID- 29336696
TI  - Controlled Adverse Environment Chambers in Dry Eye Research.
AB  - Dry eye disease (DED) is a common condition with signs and symptoms that vary
      depending on a wide range of environmental factors to which people are exposed in
      their daily lives. Factors such as variable temperature, airflow velocity,
      relative humidity, seasonality, and pollutants can alter the rate of tear film
      evaporation, improving or exacerbating symptoms of DED. Results from currently
      available clinical tests do not always correlate well with patient-reported
      symptoms, and the continually changing environment and variability in DED
      symptoms present challenges for the design and conduct of clinical trials.
      Controlled adverse environment chambers allow standardization of temperature,
      humidity, and airflow and may minimize potential confounding factors in clinical
      investigations. Their use can promote accurate study of the pathophysiology of
      DED, discovery of disease biomarkers, and assessment of the effect of various
      therapeutic approaches on patients' symptoms. Controlled adverse environment
      chambers have been used to simulate indoor surroundings such as airplane cabins
      and to test their effects on contact lens wearers. This review summarizes how
      these chambers may be useful for the development, approval, and differentiation
      of potential new treatments for DED.

PMID- 29336697
TI  - Understanding Knowledge, Attitudes, and Behaviors Toward West Nile Virus
      Prevention: A Survey of High-Risk Adults in Maryland.
AB  - OBJECTIVE: To assess knowledge, attitudes, and behaviors toward West Nile virus
      (WNV) prevention among Maryland adults >=60 years old who are at increased risk
      of severe WNV disease utilizing the health belief model. METHODS: Using a
      stratified random sample of households from zip codes with >=2 human WNV cases,
      we conducted a telephone survey of 211 Maryland adults >=60 years old between
      October and December 2012. RESULTS: Participants expressing worry about WNV were
      over thrice more likely to use insect repellent in the prior 90 days (adjusted
      odds ratio [aOR] = 3.46, 95% confidence interval [CI] = 1.33-8.95) and nearly
      thrice more likely to drain standing water around their homes than those not
      worried (aOR = 2.86, 95% CI = 1.25-6.52). Respondents perceiving a benefit in
      paying less for WNV vaccine were more likely to support mosquito control programs
      (aOR = 16.00, 95% CI = 1.50-170.68). CONCLUSIONS: Future interventions to promote
      WNV prevention among older adults should seek to enhance perceptions of
      vulnerability to WNV through risk communication, including media outreach and
      written messaging, emphasizing the benefits of personal protective behaviors.
      Community partnerships may aid in outreach to this population.

PMID- 29336698
TI  - It makes you keep trying: Life review writing for older adults.
AB  - Life review writing produces numerous psychosocial benefits for older adults, who
      are at risk for isolation and depression. This article shares findings from a
      study that examined the experiences of older adults participating in a life
      review writing group. The impact of gender composition on the group dynamic was
      also explored. Using interpretative phenomenological analysis, this study
      explored the experiences of six women and one man who participated in a life
      review writing group. Six unifying themes emerged from the research findings: (1)
      legacy, (2) connecting with others, (3) reflection, (4) vitality, (5) structure
      of the group, and (6) gender dynamics. Implications for theory, practice, and
      research are discussed.

PMID- 29336699
TI  - Persistent Ambivalence: Theorizing Queer East German Studies.
AB  - The German Democratic Republic (GDR; East Germany) had an ambivalent relationship
      with homosexuality. Under the principles of socialism, everyone was welcome to
      contribute to the greater good. The situation for queer people, here lesbians and
      gay men, was different: one of illegality and invisibility. A difficulty in
      analyzing these experiences is the theory and methodology necessary to find them
      and draw them together in a historical narrative. This essay offers a mode of
      analysis in which theories of affect illustrate long-term trends in East German
      conceptualizations of same-sex sexuality. By discussing a 1950 court ruling and a
      1989 film, the essay demonstrates the persistence of homophobic prejudice and
      fear of homosexual seduction of young people and the links to historical and
      legal developments.

PMID- 29336700
TI  - Effect of Daily Exposure to an Isolated Soy Protein Supplement on Body
      Composition, Energy and Macronutrient Intake, Bone Formation Markers, and Lipid
      Profile in Children in Colombia.
AB  - A soy protein-based supplement may optimize bone health, support physical growth,
      and stimulate bone formation. This study aimed to assess the effect of a daily
      soy protein supplement (SPS) on nutritional status, bone formation markers, lipid
      profile, and daily energy and macronutrient intake in children. One hundred seven
      participants (62 girls), ages 2 to 9, started the study and were randomly
      assigned to lunch fruit juice with (n = 57, intervention group) or without (n =
      50, control group) addition of 45 g (230 Kcal) of a commercial SPS during 12
      months; 84 children (51 girls, 33 boys) completed the study (45 and 39
      intervention and control, respectively). Nutritional assessment included
      anthropometry and nutrient intakes; initial and final blood samples were taken;
      insulin-like growth factor-I (IGF-I), osteocalcin, bone specific alkaline
      phosphatase (BAP), insulin-like growth factor binding protein-3 (IGFBP-3),
      cholesterol, triglycerides, low-density lipoprotein (LDL), and high-density
      lipoprotein (HDL) were analyzed. Statistically significant changes (p < .05) in
      body mass index and weight for age Z scores were observed between groups while
      changes in body composition were not. Changes in energy, total protein, and
      carbohydrate intakes were significantly higher in the intervention group (p <
      .01). Calorie intake changes were statistically significant between groups (p <
      .001), and BAP decreased in both groups, with values within normal ranges.
      Osteocalcin, IGFBP-3, and lipid profile were not different between groups. IGF-I
      levels and IGF/IGFBP-3 ratio increased significantly in both groups. In
      conclusion, changes in macronutrient and energy intake and nutritional status in
      the intervention group compared to control group may ensure harmonious and
      adequate bone health and development.

PMID- 29336701
TI  - Coming Out of the Shadows and the Closet: Visibility Schemas Among Undocuqueer
      Immigrants.
AB  - Centering the experiences of 31 undocuqueer immigrants, this study seeks to
      understand the ways that undocuqueer immigrants negotiate the boundaries of
      social performance by revealing or concealing their gender, sexuality, and
      immigration status. Findings of this study reveal how, in order to avoid the
      constant threat of rejection (both legal and social), undocuqueer immigrants
      engage visibility schemas and make strategic decisions about coming out of the
      shadows and the closet across different contexts. Undocuqueer immigrants'
      narratives reveal the ways the closet resembles the shadows in that both provide
      protection from the outside world, yet neither are considered suitable places for
      sustaining life. This study raises implications for both research and policy by
      considering how the intersection of gender, sexuality, and immigration status
      nullifies neoliberal narratives of coming out as an empowering process and
      illustrating the uneven landscapes of social acceptance and political control
      that undocuqueer immigrants must negotiate.

PMID- 29336702
TI  - A health agenda for Green Chemistry.

PMID- 29336704
TI  - Intent to use a web-based psychological intervention for partners of cancer
      patients: Associated factors and preferences.
AB  - This study examined partners of cancer patients intention to use a web-based
      psychological intervention, their preferences regarding its preconditions,
      functionalities and topics, and factors related to their intention. One hundred
      and sixty-eight partners completed a questionnaire about these aspects. Forty
      eight percent of the partners would (maybe) make use of a web-based intervention.
      Partners who intended to participate were significantly younger, used the
      Internet more often, and perceived more caregiver strain. Most partners preferred
      an intervention that takes less than 1 hour/week, lasts five weeks or more, and
      contains information and peer support. Half of the partners would like to receive
      online guidance.

PMID- 29336705
TI  - "Thinking about the future, what's gonna happen?"-How young people in Sweden who
      neither work nor study perceive life experiences in relation to health and well
      being.
AB  - PURPOSE: The aim of this study was to explore how young people in Sweden who
      neither work nor study perceive life experiences in relation to health and well
      being. METHODS: A task-based interview technique was used and data was analysed
      with qualitative content analysis. Interviews were conducted with 16 participants
      aged 16-20 who were unemployed and not eligible for upper secondary school, or
      who had dropped out of school. RESULTS: Three themes emerged from the analysis
      illustrating how the young people perceive their life experiences in relation to
      health and well-being: Struggling with hardships in the absence of caring
      connections, Feeling good when closely connected to others, and Being forced to
      question what has been taken for granted. Each theme consists of 2-3 subthemes.
      CONCLUSION: Based on the young people's narrated experiences health can be
      understood as: something that is created in relation to others and in relation to
      the social and cultural context; as something dynamic and changeable; as the
      ability to adapt and respond to challenges; and finally as something existing on
      a collective as well as an individual level. Implications for school, social
      services and health promotion initiatives are discussed, with an emphasis on
      working with young people.

PMID- 29336706
TI  - Family caregivers' reported nonadherence to the controller medication of asthma
      in children in Casablanca (Morocco): Extent and associated factors.
AB  - OBJECTIVE: Recent statistics show a relatively high prevalence of asthma among
      Moroccan children and a weak control over their symptoms. To our knowledge, no
      research has been carried out to document adherence to the controller treatment
      in this population. This study aims 1) to assess the extent of children's
      nonadherence to the controller treatment of asthma in an urban region of Morocco
      as reported by a family caregiver, and 2) to identify the associated factors.
      METHODS: We conducted a cross-sectional study among caregivers of asthmatic
      children (2-12 years old) in different health and education facilities of
      Casablanca-Settat. We administered face-to-face questionnaires incorporating
      validated instruments (Medication Adherence Rating Scale-Asthma (MARS-A), Beliefs
      about Medicines Questionnaire (BMQ), Asthma Knowledge Questionnaire). Univariate
      and multivariate log-binomial regressions evaluating the association between
      several factors and reported nonadherence were performed (prevalence ratios (PR)
      and 95% confidence intervals (CI)). RESULTS: Through two public hospitals, three
      private medical clinics, and one private school, 103 caregivers were recruited.
      Low adherence to the controller treatment of asthma was reported by 48% of the
      caregivers (MARS-A <45). In the multivariate model, caregivers with the lowest
      level of knowledge about asthma were almost three times more likely to report low
      adherence compared to caregivers with the highest level (PR = 2.93; 95% CI: 1.14
      7.52). CONCLUSIONS: This study highlights the finding that low adherence is
      widespread in this context and also the importance of targeting caregivers'
      knowledge of asthma for interventions.

PMID- 29336703
TI  - Establishing Correlates of Protection for Vaccine Development: Considerations for
      the Respiratory Syncytial Virus Vaccine Field.
AB  - Correlates of protection (CoPs) can play a significant role in vaccine
      development by assisting the selection of vaccine candidates for clinical trials,
      supporting clinical trial design and implementation, and simplifying tests of
      vaccine modifications. Because of this important role in vaccine development, it
      is essential that CoPs be defined by well-designed immunogenicity and efficacy
      studies, with attention paid to benefits and limitations. The respiratory
      syncytial virus (RSV) field is unique in that a great deal of information about
      the humoral response is available from basic research and clinical studies.
      Polyclonal and monoclonal antibodies have been used routinely in the clinic to
      protect vulnerable infants from infection, providing a wealth of information
      about correlations between neutralizing antibodies and disease prevention.
      Considerations for the establishment of future CoPs to support RSV vaccine
      development in different populations are therefore discussed.

PMID- 29336708
TI  - Emergency Dispatcher Stroke Recognition: Associations with Downstream Care.
AB  - OBJECTIVE: As the first point of contact for patients activating emergency
      medical services (EMS), emergency dispatchers have the earliest opportunity to
      recognize stroke. We sought to quantify dispatcher stroke recognition and its
      relationships with EMS stroke recognition and response speed. METHODS: We
      assembled a cohort of consecutive EMS-transported patients with a dispatcher
      suspected stroke or a hospital discharge diagnosis of stroke or transient
      ischemic attack (TIA). Dispatcher sensitivity and positive predictive value (PPV)
      for stroke recognition were calculated. Multivariable logistic regression
      analysis was used to determine predictors of dispatcher recognition and
      relationships between dispatcher recognition and downstream care. RESULTS: During
      a 12-month period, 601 patients met inclusion criteria. Dispatchers suspected
      stroke in 229/324 (sensitivity = 70.7% [65.5 to 75.4%]) confirmed stroke/TIA
      cases and correctly assigned a suspected stroke label in 229/506 cases (PPV =
      45.3% [41.0 to 49.6%]). Dispatchers had higher odds of recognizing ischemic
      strokes (aOR 3.4 [1.4 to 8.5]) and lower odds of recognizing patients with visual
      deficits (aOR = 0.4 [0.2 to 0.9]) or vomiting (aOR = 0.3 [0.1 to 0.9]).
      Dispatcher suspected stroke cases received more on-scene stroke screens (79.0%
      vs. 54.7%, p < 0.0001) and were more often recognized by EMS as strokes (77.7%
      vs. 57.9%, p = 0.0005). Dispatcher recognition was independently associated with
      EMS stroke recognition (aOR = 3.8 [1.9 to 7.7]), but not with transportation
      times, door-to-CT times, or t-PA delivery. CONCLUSIONS: Emergency dispatcher
      stroke recognition is associated with higher rates of on-scene stroke scale
      performance and EMS ischemic stroke recognition but not with reduced transport
      times, door-to-CT times, or t-PA treatment.

PMID- 29336707
TI  - Kyasanur Forest Disease Prevalence in Western Ghats Proven and Confirmed by
      Recent Outbreak in Maharashtra, India, 2016.
AB  - INTRODUCTION: Kyasanur forest disease (KFD) outbreak was confirmed in Dodamarg
      Taluka, Sindhudurga district (Maharashtra) in India during the year 2016. The
      rise in suspected KFD cases was reported in January 2016, peaked during March,
      and then declined gradually from April 2016. The outbreak was thoroughly
      investigated considering different socio-clinical parameters. METHODS: Total, 488
      suspected KFD cases were investigated using KFD specific real-time RT-PCR and
      anti-KFDV IgM enzyme-linked immunosorbent assay (ELISA). Sero-epidemiological
      survey was carried out in the affected area using anti-KFDV IgG ELISA. RESULTS:
      Among suspected KFD cases, high age-specific attack rate (105.1 per 1000 persons)
      was observed in adults (aged 40-59 years). Out of 488 suspected KFD cases, 130
      were laboratory confirmed. Of these, 54 cases were KFDV real-time RT-PCR
      positive, 66 cases were anti-KFDV IgM ELISA positive and 10 cases were positive
      by both the assays. Case fatality ratio among laboratory-confirmed KFD cases were
      2.3% (3/130). Majority of laboratory-confirmed KFD cases (93.1%) had visited
      Western Ghats forest in Dodamarg for activities like working in cashew nut farms
      (79.8%), cashew nut fruit collection (76.6%), collection of firewood (68.5%) and
      dry leaves/grass (40.3%), etc., before the start of symptoms. Common clinical
      features included fever (100%), headache (93.1%), weakness (84.6%), and myalgia
      (83.1%). Hemorrhagic manifestations were observed in nearly one-third of the
      laboratory-confirmed KFD cases (28.5%). A seroprevalence of (9.7%, 72/745) was
      recorded in KFD-affected area and two neighboring villages (9.1%, 15/165).
      Serosurvey conducted in Ker village showed clinical to subclinical ratio of 6:1
      in KFD-affected areas. CONCLUSION: This study confirms the outbreak of KFD
      Sindhudurg district with 130 cases. Detection of anti-KFDV IgG antibodies among
      the healthy population in KFD-affected area during the KFD outbreak suggested the
      past exposure of KFD infection. This outbreak investigation has helped health
      authorities in adopting KFD vaccination strategy for the population at risk.

PMID- 29336709
TI  - Novel Mutation of the Dystrophin Gene in a Child with Duchenne Muscular
      Dystrophy.
AB  - INTRODUCTION: Duchenne muscular dystrophy (DMD) is an X-linked autosomal
      recessive genetic disorder caused by mutations in DMD gene. Approximately 70% of
      the mutations are caused by deletions or duplications of DMD exons, while the
      remaining were minor mutations. CASE REPORT: We present a 5-year-old boy with
      typical clinical features of DMD. A novel mutation was identified as a
      c.9358_9359insA of DMD gene by next-generation sequencing. This mutation which
      was origined from mother, generated a frameshift mutation and resulted in
      abnormal synthesis of protein polypeptide chains. CONCLUSION: We demonstrated a
      novel mutation of DMD gene and expanded the spectrum of mutations causing DMD.

PMID- 29336710
TI  - Consensus Statement- Prehospital Care of Exertional Heat Stroke.
AB  - Exertional heat stroke (EHS) is one of the most common causes of sudden death in
      athletes. It also represents a unique medical challenge to the prehospital
      healthcare provider due to the time sensitive nature of treatment. In cases of
      EHS, when cooling is delayed, there is a significant increase in organ damage,
      morbidity, and mortality after 30 minutes, faster than the average EMS transport
      and ED evaluation window. The purpose of this document is to present a paradigm
      for prehospital healthcare systems to minimize the risk of morbidity and
      mortality for EHS patients. With proper planning, EHS can be managed successfully
      by the prehospital healthcare provider.

PMID- 29336712
TI  - Reliability and minimal detectable change of thoracoabdominal mobility
      measurements using photogrammetry.
AB  - The knowledge about measurement errors of the measuring tool is important before
      its use, as clinical decisions are going to be made based on its results. Here we
      investigate intrarater and interrater reliability and the minimal detectable
      change (MDC) of thoracoabdominal mobility measurements using photogrammetry,
      considering novice and experienced raters. Thoracoabdominal mobility of 17
      healthy participants was assessed; photographs during apnea in maximal
      inspiration and expiration were used to calculate latero-lateral and
      anteroposterior diameters of the thorax (at axillary and xiphoid level) and
      abdomen. One novice and one experienced rater measured the same photographs three
      times. We found good reliability for the experienced rater (average Intraclass
      Correlation Coefficient (ICC): 0.98; average MDC: 0.3) and for interrater
      comparison (average ICC: 0.97; average MDC: 0.35) for all measures, with poorer
      results for latero-lateral mobility of abdomen. The novice rater presented
      moderate reliability for latero-lateral mobility of the thorax at axillary level
      and abdomen (ICC: 0.52 and 0.61; MDC: 1.42 and 2.05, respectively) and good
      reliability for the other measures (average ICC: 0.81; average MDC: 1.52). The
      photogrammetric analysis of thoracoabdominal mobility presented itself as a
      reliable method when used by an experienced professional. However, considering
      that the measurement of latero-lateral mobility is more subjected to errors, it
      should be used with caution. The MDC presented should be taken into account as a
      threshold to be certain that the measure is not under the measurement error due
      to rater variability.

PMID- 29336711
TI  - Circulating serum interleukin-6, serum chitinase-3-like protein-1, and plasma
      vascular endothelial growth factor are not predictive for remission and
      radiographic progression in patients with early rheumatoid arthritis: post-hoc
      explorative and validation studies based on the CIMESTRA and OPERA trials.
AB  - OBJECTIVE: To investigate serum interleukin-6 (IL-6), serum chitinase-3-like
      protein-1 (YKL-40), and plasma vascular endothelial growth factor (VEGF) as
      measures of disease activity and predictors of clinical remission and
      radiographic progression in two early rheumatoid arthritis (RA) randomized
      controlled trials (RCTs). METHOD: Treatment-naive patients with early RA (< 6
      months' duration) and active disease, participating in two investigator-initiated
      RCTs, were treated according to a predefined treat-to-target algorithm aiming at
      inflammatory control, using methotrexate (MTX) + cyclosporine versus MTX +
      placebo (CIMESTRA study, n = 150, 5 year follow-up) or MTX + adalimumab versus
      MTX + placebo (OPERA study, n = 180, 2 year follow-up). The 28-joint Disease
      Activity Score (DAS28) and conventional radiography [bilateral hands and feet at
      baseline, 2 years and 5 years (only CIMESTRA)] were obtained at baseline and
      during follow-up. Serum IL-6, serum YKL-40, and plasma VEGF were measured in
      baseline blood samples and during follow-up. Hypotheses regarding the biomarkers'
      relation with DAS28 and ability to predict clinical remission (DAS28 < 2.6) and
      radiographic progression (change in total Sharp van der Heijde score >= 2) were
      generated in CIMESTRA and validated in OPERA, by Spearman's correlation and
      logistic regression analyses. RESULTS: Baseline IL-6, YKL-40, and VEGF correlated
      significantly with DAS28 in CIMESTRA (r = 0.50, r = 0.36, r = 0.36, respectively,
      all p < 0.01) and these results were confirmed in OPERA patients (r = 0.52, p <
      0.01; r = 0.18, p = 0.01; r = 0.23, p = 0.002, respectively). None of the
      biomarkers (absolute values or change) was predictive of clinical remission or
      radiographic progression at 2 or 5 years in either study. CONCLUSION: Serum IL-6,
      serum YKL-40, and plasma VEGF were significantly correlated with DAS28 at
      baseline, but did not have consistent predictive value for clinical remission or
      radiographic progression in two early RA RCTs.

PMID- 29336713
TI  - Persistent Pulmonary Hypertension Without Underlying Cardiac Disease as a
      Presentation of Pulmonary Interstitial Glycogenosis.
AB  - INTRODUCTION: Pulmonary interstitial glycogenosis (PIG) is an idiopathic lung
      condition that remains clinically underrecognized despite a growing body of
      literature. CASE REPORT: We present a case of PIG with pulmonary hypertension
      without underlying cardiac disease. This patient presented with respiratory
      distress and spontaneous pneumothorax at 6 months of age. Laboratory and imaging
      investigations demonstrated nonspecific features, but refractory pulmonary
      hypertension was confirmed on cardiac catheterization. Lung tissue histopathology
      showed glycogen positive staining of the interstitial cells, consistent with PIG.
      CONCLUSION: This unique case demonstrates that pulmonary hypertension can be seen
      in the setting of PIG without associated cardiac anomalies, and persists despite
      treatment in an otherwise self-limited condition.

PMID- 29336714
TI  - Urinary Retention and Medication Utilization on a Palliative Care Unit: A
      Retrospective Observational Study.
AB  - Urinary retention is a common problem at end-of-life that may be a result of
      medications used to control other symptoms. To determine whether use of retention
      causing drugs was associated with catheterization for urinary retention among
      palliative care unit (PCU) patients, the authors reviewed charts of 91
      consecutively admitted patients to a hospital-based PCU. Utilization of eight
      classes of retention-causing medications (opioids, antidopaminergics,
      benzodiazepines, anticholinergics, antidepressants, calcium channel antagonists,
      nonsteroidal anti-inflammatory drugs [NSAIDs], and H1 histamine antagonists) was
      compared between those catheterized for urinary retention (n = 34) and those
      never catheterized (n = 31). All patients used medication from more than one
      class of retention-causing medication. A statistically significant association
      with urinary retention occurred for antidopaminergic medications, but not other
      drug classes. The total number of classes of retention-causing medications was
      not associated with catheterization. These findings question whether urinary
      retention need hinder medication use for symptom management at end-of-life.
      Tapering of antidopaminergic medications, compared with other drug classes
      studied, may be more likely to resolve retention.

PMID- 29336715
TI  - Chronic innate immune signaling results in ubiquitination of splicing machinery.

PMID- 29336716
TI  - Reactive oxygen species, nitric oxide production and antioxidant gene expression
      during development of aerenchyma formation in wheat.
AB  - In response to hypoxia, plant roots produce very high levels of nitric oxide.
      Recently, it was demonstrated that NO and ethylene both are essential for
      development of aerenchyma in wheat roots under hypoxia. Increased NO under
      hypoxia correlated with induction of NADPH oxidase gene expression, ROS
      production and lipid peroxidation in cortical cells. Tyrosine nitration was
      prominent in cells developing aerenchyma suggesting that NO and ROS play a key
      role in development of aerenchyma. However, the role of antioxidant genes during
      development of aerenchyma is not known, therefore, we checked gene expression of
      various antioxidants such as SOD1, AOX1A, APX and MnSOD at different time points
      after hypoxia treatment and found that expression of these genes elevated in 2 h
      but downregulated in 24 h where development of aerenchyma is prominent. Further,
      we found that plants growing under ammonium nutrition displayed delayed
      aerenchyma development. Taken together, new insights presented in this short
      communication highlighted additional regulatory role of antioxidants gene
      expression during aerenchyma development.

PMID- 29336717
TI  - PD1 protein expression in tumor infiltrated lymphocytes rather than PDL1 in tumor
      cells predicts survival in triple-negative breast cancer.
AB  - To determine PD1/PDL1 expression status in triple-negative breast cancer (TNBC)
      at both protein and mRNA levels, and to analyze the relationship between their
      expression and clinical parameters of the TNBC patients. Immunohistochemistry and
      RNAscope were used to semi quantitively evaluate PD1/PDL1 protein and mRNA
      expression in 195 TNBC cases on tissue microarrays. Tumor infiltrating lymphocyte
      (TILs) abundance was assessed using hematoxylin-eosin staining. Both tumor cells
      and TILs expressed PDL1. PDL1 protein and mRNA positivity was 6.7% and 74.4%
      respectively in tumor cells, and 31.3% and 50.9% respectively in TILs. PDL1
      protein and mRNA expressions had no significant association with patient
      prognosis. PD1 protein was only detected in TILs (70.3% positivity). PD1 protein
      expression was significantly related to PDL1 expression, higher TIL abundance, Ki
      67 index, basal-like subtypes, and distant metastasis. Furthermore, it was
      significantly associated with longer disease free survival (P<0.001) and overall
      survival (P = 0.004). There was no significant association between PD1 mRNA
      expression and clinicopathological characteristics. PD1/PDL1 protein and mRNA
      expressions were inconsistent (kappa = 0.705 and 0.061, respectively). PD1
      protein expression in TILs, but not PDL1 in tumor cells, was a favorable
      prognostic factor in TNBC. PD1/PDL1 mRNA and protein expressions were
      inconsistent.

PMID- 29336718
TI  - Effect of Irvingia gabonensis on Metabolic Syndrome, Insulin Sensitivity, and
      Insulin Secretion.
AB  - The aim of this study was to evaluate the effect of Irvingia gabonensis on
      metabolic syndrome (MetS), insulin sensitivity, and insulin secretion. A
      randomized, double-blind, placebo-controlled clinical trial was performed in 24
      patients with MetS in accordance with the International Diabetes Federation
      criteria. Twelve patients received I. gabonensis (150 mg) twice a day during 90
      days, and 12 patients received placebo. Glucose and insulin concentrations were
      measured during a 2-h oral glucose tolerance test. Also, lipid profile,
      creatinine, uric acid, and hepatic enzymes were determined. The area under the
      curve (AUC) of glucose and insulin, total insulin secretion, first phase of
      insulin secretion, and insulin sensitivity were calculated. Data were tested
      using non-parametric tests. The Ethics Committee approved the protocol. After I.
      gabonensis administration, significant decreases in waist circumference (WC)
      (94.0 +/- 8.0 vs. 91.0 +/- 8.2 cm, P < .01), glucose 90' (10.0 +/- 2.5 vs. 8.6 +/
      2.7 mmol/L, P < .05), glucose 120' (8.8 +/- 2.4 vs. 7.6 +/- 2.7 mmol/L, P <
      .05), triglycerides (2.5 +/- 1.2 vs. 2.0 +/- 1.1 mmol/L, P < .05), very low
      density lipoproteins (VLDL) (0.5 +/- 0.2 vs. 0.4 +/- 0.2 mmol/L, P < .05), and
      AUC of glucose (694 +/- 142 vs. 629 +/- 172 mmol/L/min, P < .05) were found.
      Seven patients (58.3%) of the I. gabonensis group showed remission of MetS and
      two patients (16.7%) of the placebo group (P = .045). I. gabonensis lead to
      remission of MetS in 58.3% of the patients and significantly decreased WC,
      glucose 90', glucose 120', triglycerides, VLDL, and AUC of glucose.

PMID- 29336719
TI  - Bidirectional Relationships between Alcohol-Specific Parental Socialization
      Behaviors and Adolescent Alcohol Misuse.
AB  - BACKGROUND: Although numerous studies have examined parental influence on
      adolescent alcohol misuse, few have examined how adolescents impact parental
      behavior or the reciprocal nature of parent-adolescent behavior relative to
      alcohol misuse. OBJECTIVES: This study assessed bidirectional relationships
      between adolescent alcohol misuse and three alcohol-specific parenting behaviors
      (substance-specific monitoring, permissive communication messages about alcohol,
      and cautionary communication messages about alcohol). METHODS: Data were from
      1,645 parent-adolescent dyads drawn from a longitudinal study spanning grades 6
      10. A multivariate latent curve model with structured residuals was used to test
      study hypotheses. RESULTS: One marginally significant result emerged (increased
      alcohol misuse leads to greater substance-specific monitoring) after accounting
      for underlying developmental processes. CONCLUSIONS: Though practical
      implications are limited based on the results of the study, further directions
      for research regarding study design and measurement are provided to more fully
      examine dynamic processes between parents and adolescents relative to alcohol
      use.

PMID- 29336720
TI  - A novel 4-phenyl amino thiourea derivative designed for real-time ratiometric
      colorimetric detection of toxic Pb2.
AB  - The objective of this study was to develop a ratiometric and colorimetric organic
      sensor for Pb2+ detection in environmental samples. A new probe 4-phenyl amino
      thiourea (PAT) was designed and synthesized using hydrazine hydrate and phenyl
      isothiocyanate as raw materials. After its structure was characterized and
      confirmed, its UV-vis spectral property was investigated in detail. PAT possesses
      a specifically real-time, ratiometric and colorimetric response to Pb2+ in
      dimethyl formamide (DMF)/H2O (v/v = 9:1, pH = 7.0) within 18.0 s. There was
      little interference in the presence of some other common metal ions, such as
      Fe3+, Cd2+, Zn2+, Mg2+, Cr3+, Ca2+, Ba2+, Sn2+, Na+, Mn2+, Hg2+, and Pb2+. Under
      the optimized conditions (DMF/H2O with v/v of 9:1, cPAT = 1.0 * 10-3 mol.L-1, pH
      = 7.0), the present sensor PAT was successfully applied for Pb2+ determination in
      environmental water samples with satisfied recoveries (83.0%-106.0%) and
      analytical precision (<=7.2%). The recognition mechanism was confirmed to form a
      stable 1:1 six-member ring complex between the target dye and Pb2+ with a
      coordination constant of 4.96 * 104.

PMID- 29336721
TI  - Using hydrogen peroxide to prevent antibody disulfide bond reduction during
      manufacturing process.
AB  - During large-scale monoclonal antibody manufacturing, disulfide bond reduction of
      antibodies, which results in generation of low molecule weight species, is
      occasionally observed. When this happens, the drug substance does not meet
      specifications. Many investigations have been conducted across the
      biopharmaceutical industry to identify the root causes, and multiple strategies
      have been proposed to mitigate the problem. The reduction is correlated with the
      release of cellular reducing components and depletion of dissolved oxygen before,
      during, and after harvest. Consequently, these factors can lead to disulfide
      reduction over long-duration storage at room temperature prior to Protein A
      chromatography. Several strategies have been developed to minimize antibody
      reduction, including chemical inhibition of reducing components, maintaining
      aeration before and after harvest, and chilling clarified harvest during holding.
      Here, we explore the use of hydrogen peroxide in clarified harvest bulk or cell
      culture fluid as a strategy to prevent disulfide reduction. A lab-scale study was
      performed to demonstrate the effectiveness of hydrogen peroxide in preventing
      antibody reduction using multiple IgG molecules. Studies were done to define the
      optimal concentration of hydrogen peroxide needed to avoid unnecessary
      oxidization of the antibody products. We show that adding a controlled amount of
      hydrogen peroxide does not change product quality attributes of the protein.
      Since hydrogen peroxide is soluble in aqueous solutions and decomposes into water
      and oxygen, there is no additional burden involved in removing it during the
      downstream purification steps. Due to its ease of use and minimal product impact,
      we demonstrate that hydrogen peroxide treatment is a powerful, simple tool to
      quench reducing potential by simply mixing it with harvested cell culture fluid.

PMID- 29336722
TI  - Perceptions on technology for volunteer respite care for bedridden elders in
      Chile.
AB  - PURPOSE:  Informal caregivers of bedridden elders need a respite. One form of
      obtaining a respite is through volunteers who are contacted by means of
      information and communication technology (ICT). METHOD:  A qualitative study was
      carried out in a low-income district in Santiago, Chile, to learn about how
      caregivers of bedridden elders perceive the possibility of using ICT to access
      this respite. In-depth interviews were carried out and transcribed verbatim, then
      analysed using open coding. Results: The results reveal that caregivers are
      willing to receive a volunteer in their home and use ICT to communicate with
      them, although a discrepancy exists between the use of devices connected to the
      Internet and feature phones. Conclusion: This study concludes that informal
      caregivers of bedridden elders have a favourable disposition towards accessing a
      respite system by means of ICT based on a peer-to-peer economy.

PMID- 29336723
TI  - Chemical characterization and evaluation of the antioxidants in Chaenomeles
      fruits by an improved HPLC-TOF/MS coupled to an on-line DPPH-HPLC method.
AB  - An improved method based on HPLC-TOF/MS was developed to catalog the antioxidants
      in five species of Chaenomeles (Mugua). Forty-four fractions from the Mugua
      extracts show appreciable levels of antioxidative activity in scavenging the
      stable free-radical 2,2-diphenyl-1-picrylhydrazyl and the hydroxyl radicals.
      Twelve major antioxidant's chemical structures are identified. Antioxidant
      activities differ between species, but intra-species level of antioxidants,
      regardless of their ripeness, are similar. C. sinensis has the highest
      antioxidant level. A rigorous quality control procedure was implemented to ensure
      accuracy of antioxidant quantification. This improved procedure can be used for
      rapid discovery of antioxidants in other plant extracts.

PMID- 29336724
TI  - Explicit Awareness does not Modulate Retrograde Interference Effects in Sequence
      Learning.
AB  - Motor sequences are learned explicitly or implicitly based on conscious awareness
      of the sequence. Interference happens when two sequences are learned
      successively. Here, we aimed to determine whether implicit and explicit sequence
      learning are affected differently by retrograde interference. Young healthy
      volunteers participated in either a control or interference group and either an
      explicit or implicit learning condition. We used a modified serial reaction time
      task to induce sequence learning and control awareness. Results showed that the
      overall amount of sequence learning was greater in the explicit condition
      compared to implicit. However, sequence learning was equally susceptible to
      retrograde interference under either condition. We conclude that although
      susceptible to interference, explicit awareness improves overall sequence
      learning compared to implicit conditions.

PMID- 29336725
TI  - Adaptability of mitosporic stage in Sphaerodes mycoparasitica towards its
      mycoparasitic-polyphagous lifestyle.
AB  - Sphaerodes mycoparasitica Vuj. is a Fusarium-specific mycoparasite. Some recent
      discoveries recognize its biotrophic polyphagous lifestyle as an interesting
      biocontrol property against a broad spectrum of mycotoxigenic Fusarium hosts.
      Secondary metabolites such as mycotoxins produced by Fusarium spp. may play an
      important role in the signaling process, allowing an early mycoparasite-host
      recognition. A multiple-paper-disc assay has been conducted to test S.
      mycoparasitica hyphal adaptability to filtrates of 12 Fusarium spp. This study
      shows that shifts of adapted and nonadapted hyphal migration towards different
      Fusarium-host filtrates may partly explain S. mycoparasitica polyphagous
      lifestyle, and its adaptability depending on host preference or compatibility. In
      terms of host compatibility, the current findings suggest that S. mycoparasitica
      tends to prefer native Fusarium hosts more related to its origin and propose that
      the mycoparasite could possess diphasic interactions such as biotrophic
      attraction and antagonistic-inhibition relationships based on relative radial
      growth. This implies that the mycoparasite may use a group of mycotoxins produced
      by specific Fusarium spp. as an adaptive selective mechanism that facilitates a
      parasite-host recognition and further successful mycoparasitism. In particular,
      relative polarity or hydrophilicity/hydrophobicity of mycotoxins may be related
      to solubility and absorption properties in hyphae of the mycoparasite. Taken
      together, the studies of host compatibility and adaptability depending on host
      filtrates will aid in understanding complex mechanisms of S. mycoparasitica, as a
      promising model organism for a specific biotrophic mycoparasite to enhance and
      improve biocontrol efficacy against Fusaria.

PMID- 29336726
TI  - Parallel dual-task processing and task-shielding in older and younger adults:
      Behavioral and diffusion model results.
AB  - : Background/Study Context: The study investigated the Backward Crosstalk Effect
      (BCE) in dual-task situations, that is, the observation that Task 2
      characteristics can even influence Task 1 processing. This observation suggests
      that the tasks are processed in parallel. Besides determining the existence of a
      BCE in a group of older adults, the size of the BCE was compared to that in a
      group of younger adults. Importantly, recent studies yielded unclear results.
      METHODS: Twenty-four younger and older adults (19-27 and 58-71 years of age,
      respectively) performed a dual-task experiment, where Task 1 required a
      left/right manual response and Task 2 required a left/right foot response. The
      BCE manifests in shorter Task 1 RTs if both responses are given on the same side
      (compatible) compared to when they are given on different sides (incompatible).
      Data were analyzed by Analyses of Variance and diffusion modeling. RESULTS: Both
      age groups clearly exhibited a BCE, and the BCEs were of the same size. Further,
      for both age groups, the size of the BCE was similarly modulated by the previous
      trial's compatibility status. Diffusion model analyses attribute the BCE to an
      increased drift rate in compatible compared to incompatible trials, and also
      revealed no age group differences in any of the analyzed parameters. CONCLUSION:
      The results point to an aspect of cognition that seems not to show age-related
      deteriorations, similar to, for example, n-2 repetition costs in task-switching
      situations. Certain response selection-related aspects of task processing are
      processed in parallel to the same degree in younger and older adults, and both
      age groups are similarly able to shield Task 1 processing from interfering Task 2
      processing in a dual-task situation.

PMID- 29336728
TI  - The efficacy of cognitive interventions for improving cognitive performance and
      academic achievement in children after cancer treatment: A systematic review.
AB  - Academic decline has been reported in children after cancer treatment, believed
      to be as a result of cognitive impairment. Cognitive interventions may improve
      both the present and future outcomes for children after cancer treatment by
      improving cognitive and/or academic performance. This review aimed to examine the
      efficacy of cognitive interventions in children who had received cancer
      treatment. A systematic search of the PsycInfo and PubMed databases was conducted
      in May 2015 to identify studies in which cognitive interventions were conducted
      with children who had undergone cancer treatment and were under the age of 21.
      Cognitive or academic outcomes needed to be reported pre- and post-intervention
      to meet the inclusion criteria. Eleven studies were included in this review.
      Computerized and home-based cognitive interventions were found to be most
      successful at improving cognitive skills. However, few cognitive interventions
      assessed academic achievement specifically. Future cognitive intervention
      research studies should include measures of academic achievement outcomes,
      because academic achievement and cognitive outcomes may differ. Future research
      regarding the effectiveness of early, home-based and computerized intervention is
      warranted.

PMID- 29336727
TI  - Providing services to trafficking survivors: Understanding practices across the
      globe.
AB  - PURPOSE: Human trafficking is a global issue, with survivors representing all
      genders, ages, races, ethnicities, religions, and countries. However, little
      research exists that identifies effective practices in supporting survivors of
      human trafficking. The research that does exist is Western-centric. To fill this
      gap in the literature, the goal of this research was to understand practices used
      throughout the globe with adult human trafficking survivors. METHODS: A
      qualitative approach was utilized. Providers from 26 countries, across six
      different continents, were interviewed to allow for a comprehensive and multi
      faceted understanding of practices in working with survivors. RESULTS:
      Participants identified utilizing an empowerment-based, survivor, and human life
      centered approach to working with survivors, emphasized the importance of
      engaging in community level interventions, and highlighted the importance of
      government recognition of human trafficking. DISCUSSION: Findings provide
      information from the perspective of advocates on best practices in the field that
      can be used by agencies to enhance human trafficking programming.

PMID- 29336729
TI  - The victim-offender overlap in late adulthood.
AB  - This study contributes to the general knowledge of the victim-offender overlap by
      determining whether the phenomenon exists among older adults and whether known
      correlates of crime and victimization explain the relationship. Cross-sectional
      survey data from telephone interviews conducted with individuals 60 years and
      older (N = 2,000) residing in Arizona and Florida are used to estimate
      confirmatory factor models for both victimization and criminal offending. The
      results from a series of multivariate regression models show that victimization
      is associated with criminal offending. While factors such as low self-control,
      depression, and spending time in commercial drinking establishments partially
      attenuate the victimization-crime link, the statistically significant
      relationship persists in a multivariate context. Further testing indicates that
      the observed findings are robust across measurement and modeling strategies.
      Coupled with prior research, the results support the argument that the victim
      offender overlap exists (and is difficult to explain) over the life course.

PMID- 29336730
TI  - Motor and Visual-spatial Cognition Development in Primary School-Aged Children in
      Cameroon and Germany.
AB  - It was the main goal of this study to investigate the motor and visual-spatial
      development in primary school-aged children in Cameroon and Germany. Thirty-four
      children from each country completed a motor test and a mental rotation test. It
      was found that children in Cameroon showed a better motor ability (better overall
      gross motor score and also on most single items) than children in Germany did.
      This can be explained by the early motor stimulation in infancy in Cameroon.
      Concerning mental rotation performance, Cameroonian children perform below chance
      level. A positive correlation between the overall motor ability and mental
      rotation performance could only be analyzed and conducted in the German sample.
      Therefore, this study emphasizes the need for the development of culture-fair
      cognitive tests.

PMID- 29336731
TI  - Lead induces DNA damage and alteration of ALAD and antioxidant genes mRNA
      expression in construction site workers.
AB  - Oxidative stress and DNA damage are considered as possible mechanisms involved in
      lead toxicity. To test this hypothesis, DNA damage and expression variations of
      aminolevulinic acid dehydratase (ALAD), superoxide dismutase 2 (SOD2), and 8
      oxoguanine DNA glycosylase 2a (OGG1-2a) genes was studied in a cohort of 100
      exposed workers and 100 controls with comet assay and real-time polymerse chain
      reaction (PCR). Results indicated that increased number of comets was observed in
      exposed workers versus controls (p < 0.001). After qPCR analysis, significant
      down-regulation in ALAD (p < 0.0001), SOD2 (p < 0.0001), and OGG1-2a (p < 0.0001)
      level was observed in exposed workers versus controls. Additionally, a positive
      spearmen correlation was observed between ALAD versus SOD2 (r = 0.402**, p <
      0.001), ALAD versus OGG1-2a (r = 0.235*, p < 0.05), and SOD2 versus OGG1-2a (r =
      0.292*, p < 0.05). This study showed that lead exposure induces DNA damage, which
      is accompanied by an elevated intensity of oxidative stress and expression
      variation of lead-related gene.

PMID- 29336732
TI  - "Some University Lecturers Wear Gay Pride T-shirts. Get Over It!": Denials of
      Homophobia and the Reproduction of Heteronormativity in Responses to a Gay-Themed
      T-shirt.
AB  - This article explores an incident involving a gay pride T-shirt, printed with the
      slogan "Some people are gay. Get over it!," that I wore during a university
      lecture, and students' predominantly negative responses to it. I use the lens of
      modern prejudice research, particularly discursive psychological approaches to
      modern prejudice, to interpret the students' responses to a qualitative survey
      about their views on the T-shirt. They related strong feelings of upset and
      anger, particularly because I had-in their view-implicitly accused them of being
      homophobic. They passionately refused this supposed accusation on the grounds
      that "everything's equal now" and "gay people are no different from us." I argue
      that the ideological themes of cultural heterosexism and compulsory
      heterosexuality provide a productive framework for making sense of the students'
      responses, as they sanction a rational neoliberal subject who is both non
      homophobic and inculcated into heteronormativity.

PMID- 29336733
TI  - Impaired Visuospatial Short-Term Memory in Children with ADHD.
AB  - Previous studies provide clear evidence that visuospatial memory performance in
      children with attention-deficit/hyperactivity disorder (ADHD) is significantly
      lower than in typically developing children. In the present study, we
      investigated a major cause of their low performance using a spatial span test.
      Possibly, inattention resulting from lack of motivation or interest causes their
      low performance so that they do not correctly encode targets to be remembered. On
      the other hand, a deficit in temporary maintenance per se may cause their low
      performance; that is, their inefficient use of rehearsal during a retention
      interval may lead to memory traces' fast decay. Results in this study indicated
      that children with ADHD could sustain attention during the encoding phase.
      Furthermore, their performance at delayed recall was significantly lower than
      immediate recall, but delayed recall did not affect typically developing
      children's performance. These results provide evidence for the likelihood that a
      factor causing children with ADHD difficulty in temporarily maintaining
      visuospatial information is fast decay of memory traces as a result of
      inefficient use of rehearsal, not inattention in the encoding phase.

PMID- 29336734
TI  - The relationship between women's characteristics and herbal medicines use during
      pregnancy.
AB  - The use of herbal medicines (HM) has been increasing worldwide. This cross
      sectional study investigated the prevalence of and characteristics related to use
      of HM among 320 pregnant women. Participants were admitted to Mazandaran-based
      hospitals' postnatal wards from March to June 2015. Data were collected via a
      self-report questionnaire, including herbs used during pregnancy and demographic,
      socioeconomic and pregnancy-related factors. Nearly half (48.4%) of the women
      reported taking one or more HM during pregnancy. The most frequently used herbs
      were Sour orange (30.97%), Peppermint (19.81%) and Borage (19.46%). Most women
      (29.20%) were advised by their relatives to take these and did not disclose this
      use to their health care providers (50%) because they perceived their use as safe
      (39.7%). The use of herbs was greater among pregnant women with upper secondary
      level education, living in their own house and from higher socioeconomic classes.
      Most of the information sources for women were informal, indicating they were not
      knowledgeable about the herbs' safety and efficacy during pregnancy. Health care
      providers should be informed about HM and question pregnant women about their use
      of HM during pregnancy so that they can advise them about potential side effects
      and drug interactions.

PMID- 29336735
TI  - Effect of low-cost resistance training on lower-limb strength and balance in
      institutionalized seniors.
AB  - : Background/Study Context: Given the rapid increase in the aging population
      worldwide, fall prevention is of utmost importance. It is essential to establish
      an efficient, simple, safe, and low-cost intervention method for reducing the
      risk of falls. This study examined the effect of 12 weeks of progressive elastic
      resistance training on lower-limb muscle strength and balance in seniors living
      in the Rumah Seri Kenangan, social welfare home in Cheras, Malaysia. METHODS: A
      total of 51 subjects qualified to take part in this quasi-experimental study.
      They were assigned to either the resistance exercise group (n = 26) or control
      group (n = 25). The mean age of the 45 participants who completed the program was
      70.7 (SD = 6.6). The exercise group met twice per week and performing one to
      three sets of 8 to 10 repetitions for each of nine lower-limb elastic resistance
      exercises. All exercises were conducted at low to moderate intensities in sitting
      or standing positions. The subjects were tested at baseline and 6 and 12 weeks
      into the program. RESULTS: The results showed statistically significant
      improvements in lower-limb muscle strength as measured by five times sit-to-stand
      test (%Delta = 22.6) and dynamic balance quantified by the timed up-and-go test
      (%Delta = 18.7), four-square step test (%Delta = 14.67), and step test for the
      right (%Delta = 18.36) and left (%Delta = 18.80) legs. No significant changes
      were observed in static balance as measured using the tandem stand test (%Delta =
      3.25), and one-leg stand test with eyes opened (%Delta = 9.58) and eyes closed
      (%Delta = -0.61) after completion of the program. CONCLUSION: The findings
      support the feasibility and efficacy of a simple and inexpensive resistance
      training program to improve lower-limb muscle strength and dynamic balance among
      the institutionalized older adults.

PMID- 29336736
TI  - The Emergence and Persistence of Queerness: Conversing Through Visual Culture
      Within a Generation.
AB  - In this article, the authors explore the work of becoming queer within the
      Millennial generation. Collaborative in nature, their investigation turns to
      three key popular-culture texts of the 1990s-Will & Grace, Rent, and MTV's Spring
      Break-that were central to their then-emerging sense of self. Staged as an
      intragenerational conversation, the authors look to create space to unpack the
      connections, anecdotal by design, between popular texts and changing ideas of
      queer identity and community. Since neither author grew up within the confines of
      a gay ghetto-Boystown of Chicago, the Castro of San Francisco, the East Village
      of New York City-where they may have encountered and been enamored by the avant
      garde queer subcultures so often praised in queer scholarship (for important
      reasons), they turn instead to experiences with popular culture that opened up
      lessons in becoming gay, in rural and Midwestern locales where queerness operated
      and emerged differently.

PMID- 29336737
TI  - Handwashing Improvement Project-A Resident Run Success.

PMID- 29336738
TI  - Concomitant Fecal Impaction and Perforated Appendicitis in an Autistic Patient.

PMID- 29336739
TI  - Nonuterine Lipoleiomyoma.

PMID- 29336740
TI  - Primary Synchronous Bilateral Angiosarcoma of the Breast.

PMID- 29336741
TI  - Malignant Phyllodes: A Presentation of Two Patients with a Rare Disease.

PMID- 29336742
TI  - Small Bowel Obstruction from a 3-cm Gallstone in the Setting of Child-Pugh C
      Liver Cirrhosis.

PMID- 29336743
TI  - Multiple Mycotic Visceral Artery Aneurysms.

PMID- 29336744
TI  - Personal Watercraft Related Injuries-16-Year Experience from a Level I Trauma
      Center.

PMID- 29336745
TI  - Redo Gracilis Muscle Transposition for Recurrent Complex Pouch-Vaginal Fistula: A
      Feasible and Effective Pouch Salvage Surgical Procedure.

PMID- 29336746
TI  - Abdominal Splenosis Mimicking Carcinomatosis in a Patient with Acute
      Appendicitis.

PMID- 29336747
TI  - Traumatic Arteriovesical Fistula from the External Iliac Artery after Gunshot
      Wound to the Pelvis.

PMID- 29336748
TI  - An Update on the Current Management of Perforated Diverticulitis.
AB  - The management of perforated diverticulitis is a challenging aspect of general
      surgery. The prevalence of colonic diverticular disease has increased over the
      last decade and will continue to increase as the baby boomers add to the elderly
      population. Improvements in diagnostic imaging modalities, efforts to maintain
      intestinal continuity, and percutaneous drainage procedures now result in several
      alternatives when selecting a management strategy for complicated presentations.
      Specifically, laparoscopic lavage and resection with primary anastomosis have
      emerged as options for treatment of Hinchey III and IV diverticulitis in place of
      diversion in the appropriately selected patient. Percutaneous drainage of Hinchey
      II diverticulitis in centers equipped with interventional radiology provides
      another minimally invasive adjunct. The objective of this paper is to provide an
      update on the current management of perforated diverticulitis, with a focus on
      the advantages and disadvantages of the surgical options for the treatment of
      Hinchey III and IV diverticulitis.

PMID- 29336749
TI  - Heroic Measures for an American Hero: Attempting to Save the Life of General
      Douglas MacArthur.
AB  - General Douglas MacArthur was a towering public figure on an international stage
      for the first half of the 20th century. He was healthy throughout his life but
      developed a series of medical problems when he entered his 80s. This article
      reviews the General's medical care during two separate life-threatening medical
      crises that required surgical intervention. The first episode occurred in 1960
      when MacArthur presented with renal failure due to an obstructed prostate. Four
      years later after his 84th birthday, MacArthur developed bile duct obstruction
      from common duct stones. He underwent an uncomplicated cholecystectomy and common
      duct exploration but developed variceal bleeding requiring an emergent
      splenorenal shunt. His terminal event was precipitated by strangulated bowel in
      long-ignored very large inguinal hernias. MacArthur died, despite state-of-the
      art surgical intervention, due to renal failure and hepatic coma.

PMID- 29336750
TI  - Percutaneous versus Cut-Down Technique for Indwelling Port Placement.
AB  - The superiority of surgical cut-down of the cephalic vein versus percutaneous
      catheterization of the subclavian vein for the insertion of totally implantable
      venous access devices (TIVADs) is debated. To compare the safety and efficacy of
      surgical cut-down versus percutaneous placement of TIVADs. This is a single
      institution retrospective cohort study of oncologic patients who had TIVADs
      implanted by 14 surgeons. Primary outcomes were inability to place TIVAD by the
      primary approach and postoperative complications within 30 days. Multivariate
      analysis was performed by logistic regression. Secondary outcomes included
      operative time. Two hundred and forty-seven (55.9%) percutaneous and 195 (44.1%)
      cephalic cut-down patients were identified. The 30-day complication rate was 5.2
      per cent: 14 patients (5.7%) in the percutaneous and nine (4.6%) in the cut-down
      group. The technique was not a significant predictor of having a 30-day
      complication (odds ratio = 0.820; 95% confidence interval 0.342-1.879).
      Implantation failure was observed in 16 percutaneous patients (6.5%) and 28 cut
      down patients (14.4%) (adjusted odds ratio for cephalic vs cut-down = 2.387; 95%
      confidence interval 1.275-4.606). The median operative time for percutaneous
      patients was 46 minutes (interquartile range = 35, 59) versus 37.5 minutes
      (interquartile range = 30, 49) for cut-down patients(P < 0.0001). Both the
      percutaneous and cut-down technique are safe and effective for TIVAD
      implantation. Operative times were shorter and the odds of implantation failure
      higher for cephalic cut-down. As implantation failure is common, surgeons should
      familiarize themselves with both techniques.

PMID- 29336751
TI  - Laparoscopic Exploration Can Salvage Recurrent Common Bile Duct Stone after
      Cholecystectomy.
AB  - Conventionally, patients suffered from recurrent common bile duct (CBD) stone
      after cholecystectomy are suggested to be treated with endoscopic retrograde
      cholangiopancreaticography. This study was designed to explore the feasibility of
      laparoscopic common bile duct exploration (LCBDE) as a salvage procedure for
      recurrent CBD calculi after cholecystectomy. A retrospective review was conducted
      of data from 65 patients who underwent LCBDE for recurrent CBD calculi after
      cholecystectomy from January 2011 to July 2015. LCBDE was successfully carried
      out in 61 cases, with a successful rate of 93.8 per cent. Three cases required
      open conversion because of serious abdominal adhesion, and one case for
      intraoperative bleeding. Postoperative bile leakage occurred in two cases, and
      bile peritonitis developed in one case; all these three patients with
      complications were fully cured by conservative treatment. A postoperative
      retained CBD stone was found in one patient, which was extracted with endoscopic
      sphincterotomy. Furthermore, it was found that the mean operative time and length
      of postoperative hospital stay were much shorter in primary closure group (n =
      49) than in T-tube drainage group (n = 12), and the hospital expense was also
      lower in primary closure group. We suggest that LCBDE could be a novel approach
      as a salvage procedure for the recurrent CBD stone after cholecystectomy, and we
      prefer to intraoperative primary closure of CBD if possible.

PMID- 29336752
TI  - External Validation of Velazquez-Gomez Severity Score Index and ATLAS Scores and
      the Identification of Risk Factors Associated with Mortality in Clostridium
      difficile Infections.
AB  - Treatment guidelines for Clostridium difficile infection (CDI) are limited by a
      lack of widely accepted clinical prediction tools (CPTs). Two published CPTs, the
      Velazquez-Gomez Severity Score Index (VGSSI) and ATLAS scores, were evaluated,
      and variables showing the greatest correlation with mortality in patients with
      CDI were identified to further develop an objective, mortality-based CPT. A
      retrospective review of the charts of 271 hospitalized patients with CDI was
      performed. VGSSI and ATLAS scores were assigned. Means and correlations of these
      scores with mortality were evaluated. Multivariate logistic regression analysis
      was performed on 32 known potential mortality predictor variables. Mortality was
      overall strongly associated with VGSSI and ATLAS scores with poor correlation
      within the intermediate ranges. Mean scores for nonsurvivors indicated poor
      calibration. The variables most associated with mortality were Age, vasopressors,
      steroids, creatinine level, and albumin. Although both CPTs revealed the ability
      to discriminate patients at greater risk for mortality, precision and overall
      calibration were lacking. Five variables were identified which had the greatest
      correlation with mortality. Utilization of these variables to enhance or modify
      the existing CPTs is suggested as the next step in the development of a useful
      and accurate mortality-based CPT for the treatment of CDI.

PMID- 29336753
TI  - Randomized Clinical Trial Comparing Low Density versus High Density Meshes in
      Patients with Bilateral Inguinal Hernia.
AB  - We present a randomized clinical trial to compare postoperative pain,
      complications, feeling of a foreign body, and recurrence between heavyweight and
      lightweight meshes in patients with bilateral groin hernia. Sixty-seven patients
      with bilateral hernia were included in our study. In each patient, the side of
      the lightweight mesh was decided by random numbers table. Pain score was measured
      by visual analogue scale, on 1st, 3rd, 5th, and 7th postoperative day, and one
      year after the surgery. There were no statistically significative differences
      between both meshes in postoperative complications. About differences of pain
      average, there were statistically significant differences only on the 1st
      postoperative day (P <0.01) and the 7th postoperative day (P <0.05). In the
      review after a year, there were no statistically significative differences in any
      parameter. In our study, we did not find statistically significative differences
      between lightweight and heavyweight meshes in postoperative pain, complications,
      feeling of a foreign body, and recurrence, except pain on 1st and 7th
      postoperative day.

PMID- 29336754
TI  - Predictors and Outcomes of Nondiagnostic Ultrasound for Acute Appendicitis in
      Children.
AB  - Ultrasound assessments of children with possible acute appendicitis (AA) are
      often nondiagnostic. We aimed to identify the predictors of nondiagnostic
      ultrasound and to investigate the outcomes. A retrospective review was conducted
      on children aged 4 to 17 years evaluated in 2013 for AA with ultrasound at a
      tertiary hospital pediatric emergency department. Demographics, clinical data,
      and outcomes were analyzed. Of 528 children, 194 (36.7%) had diagnostic
      ultrasounds and 334 (63.3%) had nondiagnostic ultrasounds. Nondiagnostic
      ultrasounds were more common after-hours (7 pm-7 am weekdays and on weekends,
      70.7%) than during business hours (7 am-7 pm weekdays; 29.3%). After-hours timing
      and female sex were identified as independent predictors of nondiagnostic
      ultrasounds (P < 0.05 for both). AA was diagnosed in 35 children with a
      nondiagnostic ultrasound (10.5%; P < 0.05). No child who underwent a
      nondiagnostic ultrasound was found to have AA with laboratory values of white
      blood cell < 11 * 103/uL and c-reactive protein (CRP) < 5 mg/dL. Children with
      nondiagnostic ultrasounds have a low likelihood of AA if white blood cell < 11
      and CRP < 5. We propose a management algorithm that we hope will help reduce
      admissions and decrease the use of computed tomography scans.

PMID- 29336755
TI  - Incorporation of Anterior Lumbosacral Spine Exposure into a General Surgical
      Practice.
AB  - Many spine surgeons enlist the aid of an "access surgeon" to provide anterior
      exposure of the lumbosacral spine. We proposed that a single, community hospital
      general surgery practice can successfully develop an anterior spine exposure
      program with acceptable clinical outcomes. One hundred and forty-three
      consecutive anterior exposures were performed between 2008 and 2014. Morbidity
      and 30-day mortality were recorded. The effects of American Society of
      Anesthesiologists Physical Status classification (ASA class) and number of levels
      exposed on length of stay (LOS) and estimated blood loss (EBL) was reported. The
      growth of the program during this period was also evaluated. During the six-year
      period, there were nine (6.3%) major complications and 17 (11.9%) minor
      complications with no 30-day mortality. The mean LOS was similar for one-level
      and two-level exposures (3.8 days). Mean LOS was higher in ASA III patients (4.4
      days) than ASA I (2.9 days) or ASA II (3.2 days). Mean EBL for one-level
      exposures (336.3 mL) was not significantly different than EBL for two-level
      exposures (425.9 mL). EBLs in ASA class III patients were greater than in class I
      and class II patients. The program began in July of 2008 with a single spine
      surgeon and one operation that year. A high of 54 procedures, with seven
      different spine surgeons, was recorded in 2013. A single, community hospital
      general surgery practice can successfully develop an anterior approach to spine
      exposure program with acceptable clinical outcomes and with sustained growth of
      the program.

PMID- 29336756
TI  - Risk Factors for Elevated Preoperative Alkaline Phosphatase in Patients with
      Refractory Secondary Hyperparathyroidism.
AB  - Elevated preoperative levels of alkaline phosphatase (ALP) in patients with
      refractory secondary hyperparathyroidism are correlated with postoperative
      hypocalcemia and mortality. The aim of this study was to identify the predictors
      of preoperative ALP in patients with secondary hyperparathyroidism. From April
      2012 to December 2015, 220 patients with refractory secondary hyperparathyroidism
      undergoing total parathyroidectomy without autotransplantation were reviewed. A
      total of 164 patients presented with elevated preoperative ALP. Univariate
      analysis showed that patients with elevated ALP were significantly younger. The
      elevated ALP group had significantly higher levels of preoperative parathyroid
      hormone (PTH), lower preoperative serum calcium, higher preoperative phosphorus,
      lower postoperative hypocalcemia, and a longer hospital stay. Logistic regression
      analysis showed that elevated preoperative PTH was a significant independent risk
      factor for elevated preoperative ALP (P = 0.000), and its value of 1624 pg/mL was
      the optimal cutoff point. Factors predictive of elevated preoperative ALP in
      patients with secondary hyperparathyroidism include preoperative PTH. Earlier
      surgery, aggressive calcium supplementation, and more careful or aggressive
      postoperative care for high-risk patients are needed.

PMID- 29336757
TI  - Radiofrequency Thermal Ablation Heat Energy Transfer in an Ex-Vivo Model.
AB  - Little work has been done to consider the temperature changes and energy transfer
      that occur in the tissue outside the vein with ultrasound-guided vein ablation
      therapy. In this experiment, a Ex-Vivo model of the human calf was used to
      analyze heat transfer and energy degradation in tissue surrounding the vein
      during endovascular radiofrequency ablation (RFA). A clinical vein ablation
      protocol was used to determine the tissue temperature distribution in 10 per cent
      agar gel. Heat energy from the radiofrequency catheter was measured for 140
      seconds at fixed points by four thermometer probes placed equidistant radially at
      0.0025, 0.005, and 0.01 m away from the RFA catheter. The temperature rose 1.5
      degrees C at 0.0025 m, 0.6 degrees C at 0.005 m, and 0.0 degrees C at 0.01 m from
      the RFA catheter. There was a clinically insignificant heat transfer at the
      distances evaluated, 1.4 +/- 0.2 J/s at 0.0025 m, 0.7 +/- 0.3 J/s at 0.0050 m,
      and 0.3 +/- 0.0 J/s at 0.01 m. Heat degradation occurred rapidly: 4.5 +/- 0.5 J
      (at 0.0025 m), 4.0 +/- 1.6 J (at 0.0050 m), and 3.9 +/- 3.6 J (at 0.01 m).
      Tumescent anesthesia injected one centimeter around the vein would act as a heat
      sink to absorb the energy transferred outside the vein to minimize tissue and
      nerve damage and will help phlebologists strategize options for minimizing
      damage.

PMID- 29336758
TI  - Occult Appendiceal Neoplasms in Acute and Chronic Appendicitis: A Single
      Institution Experience of 1793 Appendectomies.
AB  - The incidence of appendiceal neoplasms may have been underreported in the past.
      Patients undergoing incidental appendectomies or appendectomies for chronic
      appendicitis may be at higher risk for an incidental appendiceal neoplasm. To
      determine the incidence of occult appendiceal neoplasms and identify risk factors
      associated with this pathology, a retrospective review of a pathology specimen
      database was conducted from November 2007 to December 2011, in a single tertiary
      care hospital center. All patients with appendectomies were included for analysis
      (n = 1793). Pathology specimens were grouped based on the indication for
      appendectomy, and the incidence of appendiceal neoplasms, and patient variables
      among the groups were compared using chi2 test and Student's t test. A total of
      1793 appendectomy specimens met criteria for evaluation. The total number of
      appendiceal neoplasms was 31 (1.7%). There were 14 neoplasms in 1337 (1.0%) cases
      of acute appendicitis with 2 in 41 (4.9%) cases of chronic and 15 in 415 (3.6%)
      cases, where an incidental appendectomy was performed (P < 0.001). Patients with
      carcinoid tumors were significantly younger than patients with noncarcinoid
      tumors (P = 0.0001). Indication for operation was the only significant factor for
      predicting an appendiceal tumor on final pathology. Patients who undergo interval
      or incidental appendectomies may be at higher risk of appendiceal neoplasm
      compared with those performed for other indications. Younger patients may be at a
      higher risk of occult appendiceal carcinoid neoplasms than other age groups.
      Pathologic diagnosis in specific high-risk patient groups may be the only way to
      effectively capture these tumors for optimal treatment.

PMID- 29336759
TI  - Robotic Rectopexy for Rectal Prolapse in Pediatric Patients.
AB  - Rectal prolapse is the protrusion of the rectum out of the anus. Surgical
      correction can be accomplished via open and minimally invasive abdominal
      approaches, as well as from the perineum. Robotic rectopexy is an option for
      minimally invasive treatment of rectal prolapse. There are no studies that have
      established the efficacy of robotic rectopexy for rectal prolapse in the
      pediatric population. The aim of this study was to review the experience of
      robotic rectopexy at a single institution. This is a retrospective review of our
      pediatric robotic rectopexy experience from 2012 to 2015. Information was
      obtained from chart review of both operative notes and clinic visits. Four
      pediatric patients underwent a robotic rectopexy for rectal prolapse from 2012 to
      2015. Three patients were male and one was female. The mean age was 15.5 years
      (range 13-17). Two patients had rectal prolapse with chronic constipation. One
      patient had rectal prolapse from Ehlers Danlos syndrome, and the last had rectal
      prolapse after imperforate anus repair as an infant. Three patients received a
      bowel preparation. Three patients were completed robotically, and one patient
      required conversion to an open procedure. The average postoperative length of
      stay was 3.25 days (range 2-4). There were no episodes of recurrent prolapse. Two
      patients had improvement in constipation, one had no improvement, and one had no
      documented change. Average postoperative follow-up was 11.5 months (range 3-29).
      This study was a review of one institution's experience with pediatric robotic
      rectopexy. With short-term follow-up, there was no recurrence of prolapse.
      Robotic rectopexy provided a safe, reliable, and short-term resolution of rectal
      prolapse in pediatric patients.

PMID- 29336760
TI  - Cancer Frequency in Retrosternal Goiter.
AB  - Retrosternal goiter prevalence is 5 to 40 per cent according to classifications
      in goiter series. Goiters with mediastinal extension were reported to be related
      with higher cancer rates. In our study, we aimed to investigate whether cancer
      incidence increased in retrosternal goiters compared with the cervical ones.
      Three hundred and ninety consecutive patients, who had surgery because of
      retrosternal goiter in Istanbul University Medical Faculty Department of General
      Surgery between 2005 and 2015 were included in the study (Group 1). Control group
      included 880 patients who had surgery because of nontoxic multinodular goiter in
      the same period (Group 2). Preoperative ultrasonography (USG) was performed to
      each patient. Fine-needle aspiration biopsy was performed in suspicious nodules
      and results were recorded. Carcinomas in histopathological examination were
      classified as intrathorasic and extrathorasic. Diagnostic rates of USG results
      were compared with histopathologic cancer results. Papillary carcinoma was
      diagnosed in 76 patients with retrosternal goiter (19%) and in 200 patients in
      the control group (22%). No statistically significant difference was detected
      between groups regarding the tumor rates (P > 0.05). One hundred and forty-four
      tumoral foci were detected in 76 patients with papillary carcinoma in
      retrosternal goiter patients. Three hundred and seventy tumoral foci were
      detected in 200 patients with papillary carcinoma in the control group. In the
      retrosternal goiter group, 104 carcinoma lesions of 144 papillary carcinomas were
      intrathorasic (72%). No statistically significant difference was detected between
      intrathorasic (2.1 +/- 1 cm) and extrathorasic regiones (1.9 +/- 0.8 cm)
      regarding the tumor size P > 0.05. When patients with and without cancer in the
      retrosternal goiter group were compared regarding familial thyroid cancer
      history, radiation to the neck, and cervical adenopathy, no statistically
      significant difference was detected. Cancer incidence of retrosternal goiters was
      not higher than that of the cervical ones. Yet, cancer foci of retrosternal
      goiters were commonly located in the intrathorasic area and were not detected
      with USG. Depending on these findings, we suggest that all retrosternal goiters
      should be surgically treated.

PMID- 29336761
TI  - Lymphatic Permeation Predicts Systemic Recurrence in Combination with Vascular
      Involvement in Laparoscopically Resected N0 Colon Cancer.
AB  - High-risk patient selection is required in N0 colon cancer. Although a number of
      studies have suggested high-risk clinicopathological predictors, most of these
      are based on analyses in heterogeous patients in terms of surgical procedures.
      Laparoscopic surgery for colon cancer is becoming a standard procedure worldwide
      because of its less invasiveness. Accordingly, we aimed to identify bona fide
      high-risk factors of recurrence in homogeneous N0 patients who underwent
      laparoscopic surgery. Two hundred and twenty-five patients who underwent
      laparoscopic curative resection for N0 colon cancer were analyzed.
      Clinicopathological parameters were tested for their relation to survival. The 5
      year recurrence-free survival rate (RFS) was 96.1 per cent. Lymphatic involvement
      (P < 0.001), vascular involvement (P = 0.007), and size of tumor (P = 0.023) were
      significantly associated with worse prognosis in the univariate analyses.
      Lymphatic involvement was the independent prognostic factor associated with RFS
      in the multivariate analysis (P = 0.013). Importantly, lymphatic involvement
      predicts detrimental prognosis only when vascular involvement is present. The RFS
      of the patients with both lymphatic and vascular involvement was 88.9 per cent,
      whereas it was 100 per cent in the counterpart. Differentiation, vascular
      involvement preoperative carcinoembryonic antigen, and CA 19-9 levels were
      significantly associated with lymphatic involvement in a multivariate logistic
      regression analyses. The present study concludes that lymphatic involvement in
      the presence of vascular involvement may be a high risk for systemic recurrence
      in the laparoscopically resected N0 colon cancer.

PMID- 29336762
TI  - R A Cowley, the "Golden Hour," the "Momentary Pause," and the "Third Space".
AB  - R Adams Cowley (1917-1991), the Baltimore thoracic and trauma surgeon, was an
      outstanding politician and promoter of emergency medical services. His skills
      included the effective use of language, for example, identifying the critical
      time immediately after injury as a "golden hour," and describing shock as a
      "momentary pause in the act of death." Conversely, Cowley avoided the tendency of
      some contemporaries to justify massive crystalloid infusion by invoking a "third
      space." Cowley is often assumed to have originated the first two phrases, but, in
      fact, their histories go back at least to the 19th century and illustrate the
      development of surgical science. The "third space" is often assumed to have
      originated with Cowley's contemporary, Tom Shires (1925-2007), but, in fact,
      neither of them used the phrase to describe Shires' controversial theories about
      an extracellular fluid deficit after trauma. Reviewing the actual etymology of
      these terms may help clarify the history of the underlying scientific ideas and
      enable more effective communication in the future.

PMID- 29336763
TI  - Methicillin-Resistant Staphylococcus aureus in a Trauma Population: Does
      Decolonization Prevent Infection?
AB  - The purpose of this study was to determine if a decolonization regimen reduces
      the frequency of methicillin-resistant Staphylococcus aureus (MRSA) infections
      and if colonization isolates are genetically related to subsequent infectious
      strains. Trauma patients admitted to the intensive care unit with positive MRSA
      nasal swabs were randomized to either daily chlorhexidine gluconate (CHG) baths
      and mupirocin (MUP) ointment to the nares or soap and water baths and placebo
      ointment for five days. Nasal swabs performed at the end of treatment and
      invasive MRSA infections during the remaining hospitalization were compared with
      the original nasal isolate via polymerase chain reaction for genetic relatedness
      as well as CHG and MUP resistance genes. Six hundred and seventy-eight intensive
      care unit admissions were screened, and 92 (13.6%) had positive (+) MRSA nasal
      swabs over a 22-month period ending in 3/2014. After the five day treatment
      period, there were 13 (59.1%) +MRSA second nasal swabs for CHG + MUP and 9 (90%)
      for soap and water baths and placebo, P = 0.114. No isolates tested positive for
      the MUP or CHG resistance genes mupA and qacA/B but 7 of 20 (35%) contained smr.
      There were seven (31.8%) MRSA infections in the CHG group and six (60%) for soap,
      P = 0.244. All 13 patients with MRSA infections had the same MRSA isolate present
      in the original nasal swab. There was no difference in all-cause Gram-negative or
      positive infections for CHG versus soap, 12 (54.5%) versus 7 (70%), P = 0.467.
      CHG + MUP are ineffective in eradicating MRSA from the anterior nares but may
      reduce the incidence of infection. Subsequent invasive MRSA infections are
      typically caused by the endogenous colonization strain.

PMID- 29336764
TI  - Mode of Transport and Clinical Outcome in Rural Trauma: A Helicopter versus
      Ambulance Comparison.
AB  - Helicopter Emergency Medical Services (HEMS) is presumably an effective way of
      patient transport in rural trauma, yet the literature addressing its
      effectiveness is scarce. In this study, we compared the clinical outcome of rural
      trauma patients between Ground Emergency Medical Services (GEMS) and HEMS
      transportation from the beginning of 2006 to the end of 2012. Focus was placed on
      identifying factors associated with survival to discharge in these patients. Over
      the seven-year study period, 4492 patients met the inclusion criteria with 2414
      patients (54%) being transferred by GEMS and 2078 patients (46%) being
      transferred by HEMS. In comparison with GEMS, patients transferred by HEMS were
      younger men who were admitted with a higher mean Injury Severity Score and a
      lower mean Glasgow Coma Score (all Ps < 0.0001). HEMS patients were more
      frequently intubated before arrival at the trauma center (32% vs 9%, P < 0.0001)
      and were more frequently transferred to the operating room from the emergency
      department (11% vs 5%, P < 0.0001). In multivariate analysis, transfer by HEMS
      was associated with a significant increase in survival to discharge (odds ratio:
      1.57, 95% confidence interval: 1.03-2.40, P = 0.036). Blunt injury, no
      intubation, and Glasgow Coma Score >8 were also associated with significantly
      improved odds of survival to discharge (all P < 0.0001). These findings show that
      although patients transferred by HEMS arrived in less favorable clinical
      conditions, HEMS transfer was associated with significantly higher odds of
      survival in rural trauma.

PMID- 29336765
TI  - Robotic Inguinal Hernia Repair.
AB  - Laparoscopic inguinal hernia repair has certain advantages over open repair
      including less pain and earlier return to normal activity. Concurrent robotic
      inguinal hernia repair at the time of prostatectomy has been shown to have a
      lower recurrence rate than open repair. Robotic surgery adds high definition
      visualization and articulating instruments which enhances dexterity that makes
      laparoscopic hernia repair more refined. A series of robotic, laparoscopic,
      inguinal hernia repairs by a single surgeon with an extensive laparoscopic hernia
      experience at a single institution was undertaken to determine the role of
      robotic laparoscopic inguinal hernia repair in minimally invasive surgery. Five
      hundred forty-two laparoscopic inguinal hernia operations were performed from
      April 2012 through December 2015. There were 154 cases of robotic transabdominal
      preperitoneal procedures done during that time. Hospital records and follow-up
      care were prospectively reviewed and data collected for age, sex, American
      Society of Anesthesia class, and operative time. Follow-up was done at 2, 8, and
      16 weeks after surgery. All patients consented for the study. Ninety percent of
      the patients were male. Age averaged 57.04 years with a range of 21 to 85 years.
      American Society of Anesthesia averaged 2.01 with comorbidities of hypertension,
      hypercholesterolemia, and gastroesophageal reflux disease being the most common.
      Body mass index was between 19 and 31.6, averaging 24.34. Twenty-five patients
      (16%) had an umbilical hernia repair done concomitantly. Operating room time
      ranged from 25 to 140 minutes with an average of 63.6 minutes decreased as
      experience increased. One patient with a large, left scrotal hernia was converted
      to open; one patient developed perforated sigmoid diverticulitis seven days
      postop and case #5 recurred indirectly after a direct hernia repair. Four
      patients required prolonged postoperative Foley catheterization. Robotic inguinal
      hernia repair is safe and effective. Operating room time was longer than standard
      laparoscopic herniorrhaphy but decreased with experience. A single-port platform
      may have use in patients with umbilical hernias, 16 per cent, and will need to be
      studied.

PMID- 29336766
TI  - The Implications of Transfer to an Acute Care Surgical Tertiary Service.
AB  - Tertiary hospitals are increasingly called on by smaller hospitals and free
      standing emergency rooms (ERs) to provide surgical care for complex patients.
      This study assesses patients transferred to an acute care surgery service. The ER
      and transfer center logs, as well as billing data, were reviewed for 12 months
      for all cases evaluated by acute care surgery. The charts were reviewed for
      demographics, comorbidities, and outcomes. A total of 111 transferred patients
      with complete data were identified, with 59 transferred from another hospital and
      52 from a free-standing ER. The hospital transfer patients were older with more
      comorbidities, had a longer length of stay, and were more likely discharged to
      skilled care. There was no difference in the percent of patients requiring a
      procedure; however, significantly more procedures in the hospital transfer group
      were done by nonsurgical specialties Better infrastructure to monitor the impact
      of hospital transfers is warranted in the setting of the complex patient
      population transferred to tertiary hospitals.

PMID- 29336767
TI  - Surgery for Acromioclavicular Dislocation: Factors Affecting Functional Recovery.
AB  - The objective of the study is to compare the clinical outcomes of two different
      interventions for Rockwood type III (or above) acromioclavicular dislocation and
      study the factors influencing postoperative functional recovery. A total of 60
      patients with Rockwood type III (or above) acromioclavicular dislocation were
      included in the study. Patients were divided into two groups based on the
      surgical intervention: Clavicular Hook Plate Fixation (Group A) and EndoButton
      technique of Coracoclavicular Ligament Reconstruction (Group B). Constant
      shoulder score was employed for the assessment of functional recovery before and
      after the surgery. Statistical analysis was performed in terms of age, gender,
      obesity (body mass index), Constant shoulder score, compliance of rehabilitation
      guidance, and the amount of reduction loss. The Constant score was significantly
      improved after surgery (P < 0.05). The score was better in Group B compared with
      Group A in the sixth month after surgery (P < 0.05), but showed no significant
      difference in the fifteenth month. Compliance with rehabilitation guidance
      significantly affected the values of the Constant score after the surgery (P <
      0.05). Clavicular Hook Plate and EndoButton technique both are effective ways to
      treat Rockwood type III (or above) acromioclavicular dislocation. However,
      EndoButton technique is more effective for early functional recovery. Patients'
      compliance with rehabilitation guidance is critical for the functional recovery
      after surgery.

PMID- 29336768
TI  - Is Routine Continuous EEG for Traumatic Brain Injury Beneficial?
AB  - Severe traumatic brain injury (TBI) is associated with increased risk for early
      clinical and subclinical seizures. The use of continuous electroencephalography
      (cEEG) monitoring after TBI allows for identification and treatment of seizures
      that may otherwise occur undetected. Benefits of "routine" cEEG after TBI remain
      controversial. We examined the rate of subclinical seizures identified by cEEG in
      TBI patients admitted to a Level I trauma center. We analyzed a cohort of trauma
      patients with moderate to severe TBI (head Abbreviated Injury Score >=3) who
      received cEEG within seven days of admission between October 2011 and May 2015.
      Demographics, clinical data, injury severity, and costs were recorded. Clinical
      characteristics were compared between those with and without seizures as
      identified by cEEG. A total of 106 TBI patients with moderate to severe TBI
      received a cEEG during the study period. Most were male (74%) with a mean age of
      55 years. Subclinical seizures were identified by cEEG in only 3.8 per cent of
      patients. Ninety-three per cent were on antiseizure prophylaxis at the time of
      cEEG. Patients who had subclinical seizures were significantly older than their
      counterparts (80 vs 54 years, P = 0.03) with a higher mean head Abbreviated
      Injury Score (5.0 vs 4.0, P = 0.01). Mortality and intensive care unit stay were
      similar in both groups. Of all TBI patients who were monitored with cEEG,
      seizures were identified in only 3.8 per cent. Seizures were more likely to occur
      in older patients with severe head injury. Given the high cost of routine cEEG
      and the low incidence of subclinical seizures, we recommend cEEG monitoring only
      when clinically indicated.

PMID- 29336769
TI  - Processes of Health Care Delivery, Education, and Provider Satisfaction in Acute
      Care Surgery: A Systematic Review.
AB  - In recent years, significant workload, high acuity, and complexity of emergency
      general surgery conditions have led hospitals to replace the traditional on-call
      model with dedicated acute care surgery (ACS) service models. A systematic search
      of Ovid, EMBASE, and MEDLINE was undertaken to examine the impact of ACS services
      on health-care delivery processes and cost, education, and provider satisfaction.
      From 1827 papers, reviewers identified 22 studies that met inclusion criteria and
      subsequently used The Evidence-Based Practice for Improving Quality method and
      Newcastle-Ottawa Scale to score quality and level of evidence. Most studies found
      an increase in daytime operating, improved patient transit from emergency
      department to operating room to home, and decreased length of stay. Higher and
      more diverse case volumes improved resident education and operative experience.
      ACS services enhanced the educational experience of residents on subspecialty
      services by offloading emergency work from those services. Finally, surgeons
      generally felt that ACS services improved job satisfaction, productivity, and
      billing. The ACS model has demonstrated improvement in timeliness of care,
      diversified case mix, decreased costs, improved trainee learning, and increased
      surgeon job satisfaction.

PMID- 29336770
TI  - Limit Crystalloid Resuscitation after Traumatic Brain Injury.
AB  - Patients with traumatic brain injury (TBI) are often resuscitated with
      crystalloids in the emergency department (ED) to maintain cerebral perfusion. The
      purpose of this study was to evaluate whether crystalloid resuscitation volume
      impacts mortality in TBI patients. This was a retrospective study of trauma
      patients with head abbreviated injury scale score >=2, who received crystalloids
      during ED resuscitation between 2004 and 2013. Clinical characteristics and
      volume of crystalloids received in the ED were collected. Patients who received
      <2 L of crystalloids were categorized as low volume (LOW), whereas those who
      received >=2 L were considered high volume (HIGH). Mortality and outcomes were
      compared. Multivariable regression analysis was used to determine the odds of
      mortality while controlling for confounders. Over 10 years, 875 patients met
      inclusion criteria. Overall mortality was 12.5 per cent. Seven hundred and forty
      two (85%) were in the LOW cohort and 133 (15%) in the HIGH cohort. Gender and age
      were similar between the groups. The HIGH cohort had lower admission systolic
      blood pressure (128 vs 138 mm Hg, P = 0.001), lower Glasgow coma scale score (10
      vs 12, P < 0.001), higher head abbreviated injury scale (3.8 vs 3.3, P < 0.001),
      and higher injury severity score (25 vs 18, P < 0.001). The LOW group had a lower
      unadjusted mortality (10 vs 26%, P < 0.001). Multivariable analysis adjusting for
      confounders demonstrated that those resuscitated with >=2 L of crystalloids had
      increased odds of mortality (adjusted odds ratio 2.25, P = 0.005). Higher volume
      crystalloid resuscitation after TBI is associated with increased mortality, thus
      limited resuscitation for TBI patients may be indicated.

PMID- 29336771
TI  - Surgical and Endovascular Management of Patients with Chronic Mesenteric
      Ischemia: A Single Center Experience.
AB  - Chronic mesenteric ischemia is a rare intestinal disorder, with a potential
      evolution toward intestinal infraction. The choice of the appropriate treatment
      is currently the most crucial issue in the management of patients with chronic
      mesenteric ischemia. We describe our experience with 16 cases, and we discuss the
      current diagnostic and therapeutic approaches. A retrospective review of the
      clinical records was performed, and demographic, clinical, therapeutic, and
      prognostic data were collected. Six patients were females (37%), and the mean age
      was 62 years. Postprandial pain was present in all the cases, whereas sitophobia
      and weight loss were detected in 87 per cent of them. Eight patients were treated
      with open surgery; no perioperative deaths or relevant complications occurred.
      One patient had a restenosis of the celiac trunk and superior mesenteric artery
      10 months after surgery. No deaths or relevant complications occurred in the
      remaining patients, who underwent an endovascular procedure. One patient
      presented a restenosis distal to the vascular stent, whereas two patients died
      due to comorbidities. The low rates of postoperative morbidity, mortality, and
      restenosis obtained suggest that surgical or endovascular correction of chronic
      mesenteric ischemia is satisfactory when performed by experienced surgeons, with
      an adequate selection of the patients.

PMID- 29336772
TI  - tPA/DNase for Complicated Parapneumonic Effusions and Empyemas.

PMID- 29336773
TI  - Outcomes of Elderly Patients Undergoing Elective Abdominal Surgery.

PMID- 29336774
TI  - Altered cortical thickness and attentional deficits in adolescent girls and women
      with bulimia nervosa.
AB  - BACKGROUND: Frontostriatal and frontoparietal abnormalities likely contribute to
      deficits in control and attentional processes in individuals with bulimia nervosa
      and to the persistence of dysregulated eating across development. This study
      assessed these processes and cortical thickness in a large sample of adolescent
      girls and women with bulimia nervosa compared with healthy controls. METHODS: We
      collected anatomical MRI data from adolescent girls and women (ages 12-38 yr)
      with full or subthreshold bulimia nervosa and age-matched healthy controls who
      also completed the Conners Continuous Performance Test-II (CPT-II). Groups were
      compared on task performance and cortical thickness. Mediation analyses explored
      associations among cortical thickness, CPT-II variables, bulimia nervosa symptoms
      and age. RESULTS: We included 60 girls and women with bulimia nervosa and 54
      controls in the analyses. Compared with healthy participants, those with bulimia
      nervosa showed increased impulsivity and inattention on the CPT-II, along with
      reduced thickness of the right pars triangularis, right superior parietal and
      left dorsal posterior cingulate cortices. In the bulimia nervosa group,
      exploratory analyses revealed that binge eating frequency correlated inversely
      with cortical thickness of frontoparietal and insular regions and that reduced
      frontoparietal thickness mediated the association between age and increased
      symptom severity and inattention. Binge eating frequency also mediated the
      association between age and lower prefrontal cortical thickness. LIMITATIONS:
      These findings are applicable to only girls and women with bulimia nervosa, and
      our cross-sectional design precludes understanding of whether cortical thickness
      alterations precede or result from bulimia nervosa symptoms. CONCLUSION:
      Structural abnormalities in the frontoparietal and posterior cingulate regions
      comprising circuits that support control and attentional processes should be
      investigated as potential contributors to the maintenance of bulimia nervosa and
      useful targets for novel interventions.

PMID- 29336775
TI  - Neural correlates of emotional action control in anger-prone women with
      borderline personality disorder.
AB  - BACKGROUND: Difficulty in controlling emotional impulses is a crucial component
      of borderline personality disorder (BPD) that often leads to destructive,
      impulsive behaviours against others. In line with recent findings in aggressive
      individuals, deficits in prefrontal amygdala coupling during emotional action
      control may account for these symptoms. METHODS: To study the neurobiological
      correlates of altered emotional action control in individuals with BPD, we asked
      medication-free, anger-prone, female patients with BPD and age- and intelligence
      matched healthy women to take part in an approach-avoidance task while lying in
      an MRI scanner. The task required controlling fast behavioural tendencies to
      approach happy and avoid angry faces. Additionally, before the task we collected
      saliva testosterone and self-reported information on tendencies to act out anger
      and correlated this with behavioural and functional MRI (fMRI) data. RESULTS: We
      included 30 patients and 28 controls in our analysis. Patients with BPD reported
      increased tendencies to act out anger and were faster in approaching than
      avoiding angry faces than with healthy women, suggesting deficits in emotional
      action control in women with BPD. On a neural level, controlling fast emotional
      action tendencies was associated with enhanced activation in the antero- and
      dorsolateral prefrontal cortex across groups. Healthy women showed a negative
      coupling between the left dorsolateral prefrontal cortex and right amygdala,
      whereas this was absent in patients with BPD. LIMITATIONS: Specificity of results
      to BPD and sex differences remain unknown owing to the lack of clinical control
      groups and male participants. CONCLUSION: The results indicate reduced lateral
      prefrontal-amygdala communication during emotional action control in anger-prone
      women with BPD. The findings provide a possible neural mechanism underlying
      difficulties with controlling emotional impulses in patients with BPD.

PMID- 29336776
TI  - Pharmacokinetics and dose individualization of ceftriaxone in a hepatically
      impaired, critically-ill patient receiving continuous venovenous hemofiltration.

PMID- 29336777
TI  - Presence of apoptosis distinguishes primary central nervous system lymphoma from
      glioblastoma during intraoperative consultation.
AB  - AIM: To evaluate the overlapping and distinguishing cytologic features of primary
      central nervous system lymphoma (PCNSL), diffuse large B-cell lymphoma, and
      glioblastoma (GM) in frozen sections and squash smear slides. MATERIALS AND
      METHODS: Intraoperative frozen sections and squash smear slides from PCNSL (N =
      63) and GM (N = 122) patients diagnosed from 2005 to 2015 were retrieved from
      pathology records. Overlapping and distinguishing histologic features were
      examined and statistically analyzed. RESULTS: Necrosis and moderate nuclear size
      variation were common features of PCNSL and GM. PCNSL characteristically showed
      apoptosis, lack of a fibrillary background, monotonous nuclei, scant cytoplasm,
      lack of microvascular proliferation, and presence of perivascular cuffing.
      Multivariate analysis revealed that presence of apoptosis was the most powerful
      predictive parameter for the diagnosis of PCNSL. CONCLUSION: The presence of
      apoptosis was effective for the intraoperative diagnosis of PCNSL compared to
      GM.?.

PMID- 29336779
TI  - Prophylactic thyroidectomies in MEN2 syndrome: Management and outcomes.
AB  - AIM OF THE STUDY: The aim of the study was to evaluate the outcomes of
      prophylactic thyroidectomies performed in an academic setting in the context of
      multiple endocrine neoplasia type 2 (MEN2) syndrome. METHODS: A chart review of
      patients <18years old who underwent prophylactic thyroidectomy for a MEN2
      syndrome at a children's hospital between 2006 and 2015 was performed. MAIN
      RESULTS: The study included 21 patients (57% female) with a mean age of 6.2+/
      2.5years. All patients were asymptomatic at first evaluation. Nineteen had MEN2A
      syndrome with RET proto-oncogene mutations identified. The remaining two were RET
      negative with familial medullary thyroid cancer (FMTC). One patient had a
      concomitant Hirschsprung disease. Of the 11 patients who had RET proto-oncogene
      mutations ranked as Moderate Risk for medullary thyroid cancer (MTC) (American
      Thyroid Association), one had a microcarcinoma on the resected specimen, and the
      others had C-Cell Hyperplasia. Among the 8 patients who had RET proto-oncogene
      mutations ranked as High Risk level for MTC, all had microcarcinoma. Of the nine
      patients with microcarcinoma, three underwent surgery after 5years of age. No
      microcarcinoma exceeded 6mm. There were no permanent complications. Six patients
      experienced transient hypocalcemia, of which only one was symptomatic. No
      patients had lymph node involvement, and no recurrence was noted during the
      follow-up period. CONCLUSIONS: Of 21 children with familial thyroid cancer
      syndrome who underwent a prophylactic thyroidectomy, nine had microcarcinoma.
      This study highlights the need for a complete familial history, including FMTC
      history and mandatory preventive surgical approach. LEVEL OF EVIDENCE: III.

PMID- 29336778
TI  - Damage-induced reactive oxygen species regulate vimentin and dynamic collagen
      based projections to mediate wound repair.
AB  - Tissue injury leads to early wound-associated reactive oxygen species (ROS)
      production that mediate tissue regeneration. To identify mechanisms that function
      downstream of redox signals that modulate regeneration, a vimentin reporter of
      mesenchymal cells was generated by driving GFP from the vimentin promoter in
      zebrafish. Early redox signaling mediated vimentin reporter activity at the wound
      margin. Moreover, both ROS and vimentin were necessary for collagen production
      and reorganization into projections at the leading edge of the wound. Second
      harmonic generation time-lapse imaging revealed that the collagen projections
      were associated with dynamic epithelial extensions at the wound edge during wound
      repair. Perturbing collagen organization by burn wound disrupted epithelial
      projections and subsequent wound healing. Taken together our findings suggest
      that ROS and vimentin integrate early wound signals to orchestrate the formation
      of collagen-based projections that guide regenerative growth during efficient
      wound repair.

PMID- 29336780
TI  - Advances in non-contrast quiescent-interval slice-selective (QISS) magnetic
      resonance angiography.
AB  - There is a pressing clinical need to develop accurate, efficient non-contrast
      magnetic resonance angiography (NC-MRA) techniques. Our efforts in the field have
      focused on a novel non-subtractive technique called quiescent-interval slice
      selective (QISS) MRA. Compared with other NC-MRA techniques, QISS has the
      advantage of being more accurate while enabling a simpler and more efficient
      workflow. The original implementation, which uses electrocardiogram (ECG) gating
      and a Cartesian k-space trajectory, is a reliable technique for the evaluation of
      peripheral arterial disease (PAD). Recent advances in QISS technology include the
      use of a radial k-space trajectory, which facilitates rapid imaging of the
      coronary, renal, and pulmonary arteries as well as other vascular beds, and
      ungated ("UnQISS") acquisitions for PAD.

PMID- 29336781
TI  - Corrigendum to "Osteopontin promotes collagen I synthesis in hepatic stellate
      cells by miRNA-129-5p inhibition" [Exp. Cell Res. 362(2) (2018) 343-348].

PMID- 29336782
TI  - Loss of GPNMB Causes Autosomal-Recessive Amyloidosis Cutis Dyschromica in Humans.
AB  - Amyloidosis cutis dyschromica (ACD) is a distinct form of primary cutaneous
      amyloidosis characterized by generalized hyperpigmentation mottled with small
      hypopigmented macules on the trunks and limbs. Affected families and sporadic
      case subjects have been reported predominantly in East and Southeast Asian
      ethnicities; however, the genetic cause has not been elucidated. We report here
      that the compound heterozygosity or homozygosity of GPNMB truncating alleles is
      the cause of autosomal-recessive ACD. Six nonsense or frameshift mutations were
      identified in nine individuals diagnosed with ACD. Immunofluorescence analysis of
      skin biopsies showed that GPNMB is expressed in all epidermal cells, with the
      highest staining observed in melanocytes. GPNMB staining is significantly reduced
      in the lesional skin of affected individuals. Hyperpigmented lesions exhibited
      significantly increased amounts of DNA/keratin-positive amyloid deposits in the
      papillary dermis and infiltrating macrophages compared with hypo- or depigmented
      macules. Depigmentation of the lesions was attributable to loss of melanocytes.
      Intracytoplasmic fibrillary aggregates were observed in keratinocytes scattered
      in the lesional epidermis. Thus, our analysis indicates that loss of GPNMB, which
      has been implicated in melanosome formation, autophagy, phagocytosis, tissue
      repair, and negative regulation of inflammation, underlies autosomal-recessive
      ACD and provides insights into the etiology of amyloidosis and pigment
      dyschromia.

PMID- 29336783
TI  - Bronchiectasis is highly prevalent in anti-MPO ANCA-associated vasculitis and is
      associated with a distinct disease presentation.
AB  - OBJECTIVES: To assess the prevalence of bronchiectasis in a Western cohort with
      ANCA-positive granulomatosis with polyangiitis (GPA) or microscopic polyangiitis
      (MPA) and its correlations with disease presentation and outcome. METHODS:
      Retrospective study of ANCA-associated vasculitis (AAV) patients followed at
      Nantes University Hospital (2005-2015). Clinical, biological, and follow-up data
      were collected through chart review. Two experienced radiologists blinded to the
      clinical data interpreted chest high-resolution CTs according to the Feischner
      Society criteria. RESULTS: Fifty-eight patients were included: 30 had MPA (51.7%)
      and 28 had GPA (48.3%). The median age at AAV diagnosis was 65.5 years. Anti-MPO
      ANCA and anti-PR3-ANCA were present in 39 (67.2%) and 19 (32.8%) patients,
      respectively. Overall, bronchiectasis was found in 22 patients (37.9%), all of
      whom had anti-MPO ANCA. In multivariate analysis, bronchiectasis was
      independently associated with anti-MPO-ANCA, female gender and age at AAV
      diagnosis. Furthermore, anti-MPO ANCA patients with bronchiectasis had more
      frequent peripheral nerve involvement (54.5 vs. 17.6%, p = 0.019) and less
      frequent renal involvement than those without bronchiectasis (40.9% vs. 82.3%, p
      = 0.009). Disease course, survival and risk of severe pulmonary infection were
      similar in patients with and without bronchiectasis on chest CT. CONCLUSIONS:
      This study shows that bronchiectasis is a highly prevalent pre-existing
      respiratory condition in Caucasian patients with anti-MPO AAV. This subset of
      patients exhibits a distinct presentation. Further studies are needed to confirm
      these findings and clarify the clinical implications of this association. Whether
      the respiratory tract could be the site of initiation of anti-MPO auto-immunity
      remains to be investigated.

PMID- 29336784
TI  - Reflections on the utility of excess bases as a marker in the prognosis of chest
      trauma in the geriatric population.

PMID- 29336785
TI  - The erector spinae plane block in 4 cases of video-assisted thoracic surgery.
AB  - Multimodal anaesthesia, combining epidural catheter and general anaesthesia, is a
      common technique in thoracic surgery, however, epidural catheter placement is not
      always possible. Recently, erector spinae plane block has been described, which
      provides analgesia like that of the epidural block, although unilateral, and
      which has been used in various procedures at thoracic level. At present, there
      are no studies comparing the efficacy or safety of this block with those commonly
      used in thoracic surgery. However, its safety profile and contraindications seem
      different from those of the epidural catheter, since its placement is done under
      ultrasound view, the needle introduction is done in plane and the ultrasound
      target, the transverse process, is easily identifiable and is relatively remote
      from major neural or vascular structures and the pleura. Unlike other blockages
      made by anatomical references, erector spinae plane block can be done with the
      patient in different positions. We describe our experience with erector spinae
      plane block as part of a multimodal anaesthetic approach in thoracic surgery.

PMID- 29336786
TI  - A Possible Role of Takotsubo Cardiomyopathy in Ventricular Fibrillation During
      Delirium Tremens: A Case Report and Literature Review.

PMID- 29336787
TI  - Clinical Severity Alone Does Not Determine Disposition Decisions for Patients in
      the Emergency Department with Suicide Risk.
AB  - BACKGROUND: Boarding of patients with suicide risk in emergency departments (EDs)
      negatively affects both patients and society. Factors other than clinical
      severity may frequently preclude safe outpatient dispositions among suicidal
      patients boarding for psychiatric admission in the ED. OBJECTIVE: To determine
      the extent to which nonclinical factors preclude safe outpatient discharge from
      the ED among patients boarding for psychiatric admission based on suicide risk.
      METHODS: A survey regarding the importance of 13 clinical and 19 nonclinical
      barriers to safe outpatient disposition was administered in the ED to 40 adults
      who were determined by psychiatrists to require inpatient level of psychiatric
      care due to suicide risk. A second survey regarding whether addressing the
      nonclinical factors would have enabled a safe outpatient disposition in each case
      was administered to the psychiatrists who evaluated each patient participant.
      RESULTS: Out of 40 patient participants, 39 cited at least one nonclinical factor
      that could have enabled a safe outpatient disposition had it been correctable in
      the ED. According to the psychiatrists who made the decision to hospitalize, 10
      (25%) of the patient participants could have been discharged had social support
      become available. CONCLUSION: Both clinical and nonclinical factors affect
      disposition from the ED after an evaluation for suicide risk. Attention to
      nonclinical factors should be considered in programmatic efforts to reduce ED
      boarding of patients with suicide risk.

PMID- 29336788
TI  - Grey Wolf based control for speed ripple reduction at low speed operation of PMSM
      drives.
AB  - Speed ripple at low speed-high torque operation of Permanent Magnet Synchronous
      Machine (PMSM) drives is considered as one of the major issues to be treated. The
      presented work proposes an efficient PMSM speed controller based on Grey Wolf
      (GW) algorithm to ensure a high-performance control for speed ripple reduction at
      low speed operation. The main idea of the proposed control algorithm is to
      propose a specific objective function in order to incorporate the advantage of
      fast optimization process of the GW optimizer. The role of GW optimizer is to
      find the optimal input controls that satisfy the speed tracking requirements. The
      synthesis methodology of the proposed control algorithm is detailed and the
      feasibility and performances of the proposed speed controller is confirmed by
      simulation and experimental results. The GW algorithm is a model-free controller
      and the parameters of its objective function are easy to be tuned. The GW
      controller is compared to PI one on real test bench. Then, the superiority of the
      first algorithm is highlighted.

PMID- 29336789
TI  - Actuator stiction compensation via variable amplitude pulses.
AB  - A novel model free stiction compensation scheme is developed which eliminates the
      oscillations and also reduces valve movement, allowing good setpoint tracking and
      disturbance rejection. Pulses with varying amplitude are added to the controller
      output to overcome stiction and when the error becomes smaller than a specified
      limit, the compensation ceases and remains in a standby mode. The compensation re
      starts as soon as the error exceeds the user specified threshold. The ability to
      cope with uncertainty in friction is a feature achieved by the use of pulses of
      varying amplitude. The algorithm has been evaluated via simulation and by
      application on an industrial DCS system interfaced to a pilot scale process with
      features identical to those found in industry including a valve positioner.

PMID- 29336790
TI  - A multiple kernel classification approach based on a Quadratic Successive
      Geometric Segmentation methodology with a fault diagnosis case.
AB  - This work presents a new approach for solving classification and learning
      problems. The Successive Geometric Segmentation technique is applied to
      encapsulate large datasets by using a series of Oriented Bounding Hyper Box
      (OBHBs). Each OBHB is obtained through linear separation analysis and each one
      represents a specific region in a pattern's solution space. Also, each OBHB can
      be seen as a data abstraction layer and be considered as an individual Kernel.
      Thus, it is possible by applying a quadratic discriminant function, to assemble a
      set of nonlinear surfaces separating each desirable pattern. This approach allows
      working with large datasets using high speed linear analysis tools and yet
      providing a very accurate non-linear classifier as final result. The methodology
      was tested using the UCI Machine Learning repository and a Power Transformer
      Fault Diagnosis real scenario problem. The results were compared with different
      approaches provided by literature and, finally, the potential and further
      applications of the methodology were also discussed.

PMID- 29336791
TI  - Robust inertia-free attitude takeover control of postcapture combined spacecraft
      with guaranteed prescribed performance.
AB  - In this paper, a robust inertia-free attitude takeover control scheme with
      guaranteed prescribed performance is investigated for postcapture combined
      spacecraft with consideration of unmeasurable states, unknown inertial property
      and external disturbance torque. Firstly, to estimate the unavailable angular
      velocity of combination accurately, a novel finite-time-convergent tracking
      differentiator is developed with a quite computationally achievable structure
      free from the unknown nonlinear dynamics of combined spacecraft. Then, a robust
      inertia-free prescribed performance control scheme is proposed, wherein, the
      transient and steady-state performance of combined spacecraft is first
      quantitatively studied by stabilizing the filtered attitude tracking errors.
      Compared with the existing works, the prominent advantage is that no parameter
      identifications and no neural or fuzzy nonlinear approximations are needed, which
      decreases the complexity of robust controller design dramatically. Moreover, the
      prescribed performance of combined spacecraft is guaranteed a priori without
      resorting to repeated regulations of the controller parameters. Finally, four
      illustrative examples are employed to validate the effectiveness of the proposed
      control scheme and tracking differentiator.

PMID- 29336792
TI  - An Ounce of Prevention May Be Worth Many Pounds of Cure.

PMID- 29336794
TI  - Tubercular Dactylitis in a Young Boy.

PMID- 29336795
TI  - The Breathing Effort of Very Preterm Infants at Birth.
AB  - OBJECTIVE: To compare the respiratory effort of very preterm infants receiving
      positive pressure ventilation (PPV) with infants breathing on continuous positive
      airway pressure (CPAP), directly after birth. STUDY DESIGN: Recorded
      resuscitations of very preterm infants receiving PPV or CPAP after birth were
      analyzed retrospectively. The respiratory effort (minute volume and recruitment
      breaths [>8 mL/kg], heart rate, oxygen saturation, and oxygen requirement were
      analyzed for the first 2 minutes and in the fifth minute after birth. RESULTS:
      Respiratory effort was analyzed in 118 infants, 87 infants receiving PPV and 31
      infants receiving CPAP (median gestational age, 28 weeks [IQR, 26-29] vs 29 weeks
      [IQR, 29-30; P < .001); birth weight, 1059 g [IQR, 795-1300] vs 1205 g [IQR, 956
      1418; P = .06]). The minute volume of spontaneous breaths of infants receiving
      PPV was lower at 2 minutes (37 mL/kg/minute [IQR, 15-69] vs 188 mL/kg/minute
      [IQR, 128-297; P < .001]) and at 5 minutes (112 mL/kg/minute [IQR, 46-229] vs 205
      mL/kg/minute [IQR, 174-327; P < .001]). Recruitment breaths occurred less in the
      PPV group at 2 minutes (0 breaths/minute [IQR, 0-1] vs 4 breaths/minute [IQR, 1
      8; P < .001]) and 5 minutes (0 breaths/minute [IQR, 0-3] vs 2 breaths/minute
      [IQR, 0-11; P = .01). The heart rate was lower in the PPV group (94 beats/minute
      [IQR, 68-128] vs 124 beats/minute [IQR, 100-144; P = .02]) as was oxygen
      saturation (50% [IQR, 35%-66%] vs 67% [IQR, 34%-80%; P = .04]), but not different
      at 5 minutes (heart rate, 149 beats/minute [IQR, 131-162] vs 150 beats/minute
      [IQR, 132-160; P = NS]; oxygen saturation , 91% [IQR, 80%-95%] vs 92% [IQR, 89%
      97%; P = NS]). The oxygen requirement was higher (at 2 minutes, 30% [IQR, 21%
      53%] vs 21% [IQR, 21%-29%; P = .05]; at 5 minutes, 39% [IQR, 22%-91%] vs 22%
      [IQR, 21%-31%; P = .003]). CONCLUSION: Very preterm infants breathe at birth when
      receiving PPV, but the respiratory effort was significantly lower when compared
      with infants receiving CPAP only. The reduced breathing effort observed likely
      justified applying PPV in most infants.

PMID- 29336796
TI  - An Unusual Cause of Abdominal Pain.

PMID- 29336797
TI  - Deficit of Fat Free Mass in Very Preterm Infants at Discharge is Associated with
      Neurological Impairment at Age 2 Years.
AB  - Preterm infants have a deficit of fat-free mass accretion during hospitalization.
      This study suggests that z score of fat-free mass at discharge is associated with
      neurologic outcome (P = .003) at 2 years of age, independent of sex, gestational
      age, and birth weight z score. Interventions to promote quality of growth should
      be considered.

PMID- 29336793
TI  - Hand Preference and Cognitive, Motor, and Behavioral Functioning in 10-Year-Old
      Extremely Preterm Children.
AB  - The association of hand preference (left, mixed, and right) with cognitive,
      academic, motor, and behavioral function was evaluated in 864 extremely preterm
      children at 10 years of age. Left-handed and right-handed children performed
      similarly but mixed-handed children had greater odds of functional deficits
      across domains than right-handed children.

PMID- 29336798
TI  - Hospital Readmissions in Children with Pulmonary Hypertension: A Multi
      Institutional Analysis.
AB  - OBJECTIVE: To assess the rate of and risk factors for 30-day hospital readmission
      in children with pulmonary hypertension. STUDY DESIGN: The Pediatric Health
      Information System database was analyzed for patients <=18 years old with
      pulmonary hypertension (International Classification of Diseases, Ninth Revision,
      diagnosis codes of 416.0, 416.1, 416.8, or 416.9) admitted from 2005 through
      2014. A generalized hierarchical regression model was used to determine
      significant ORs and 95% CIs associated with 30-day readmission. RESULTS: A total
      of 13580 patients met inclusion criteria (median age 1.7 years [IQR 0.3-8.7],
      45.3% with congenital heart disease). Admissions increased 4-fold throughout the
      study period. Associated hospital charges increased from $119 million in 2004 to
      $929 million in 2014. During initial admission, 57.4% of patients required
      admission to the intensive care unit, and 48.2% required mechanical ventilation.
      The 30-day readmission rate was 26.3%. Mortality during readmission was 4.2%.
      Factors increasing odds of readmission included a lower hospital volume of
      pulmonary hypertension admissions (1.41 [1.23-1.57], P < .001) and having public
      insurance (1.26 [1.16-1.38], P < .001). Decreased odds of readmission were
      associated with older age and the presence of congenital heart disease (0.86
      [0.79-0.93], P < .001). CONCLUSIONS: The pediatric pulmonary hypertension
      population carries significant morbidity, as reflected by a high use of intensive
      care unit resources and a high 30-day readmission rate. Younger patients and
      those with public insurance represent particularly at-risk groups.

PMID- 29336800
TI  - Oral Granular Cell Tumor Mimicking a Giant Sialolith in a Child.

PMID- 29336799
TI  - Access to High Pediatric-Readiness Emergency Care in the United States.
AB  - OBJECTIVE: To determine the geographic accessibility of emergency departments
      (EDs) with high pediatric readiness by assessing the percentage of US children
      living within a 30-minute drive time of an ED with high pediatric readiness, as
      defined by collaboratively developed published guidelines. STUDY DESIGN: In this
      cross-sectional analysis, we examined geographic access to an ED with high
      pediatric readiness among US children. Pediatric readiness was assessed using the
      weighted pediatric readiness score (WPRS) of US hospitals based on the 2013
      National Pediatric Readiness Project (NPRP) survey. A WPRS of 100 indicates that
      the ED meets the essential guidelines for pediatric readiness. Using estimated
      drive time from ZIP code centroids, we determined the proportions of US children
      living within a 30-minute drive time of an ED with a WPRS of 100 (maximum), 94.3
      (90th percentile), and 83.6 (75th percentile). RESULTS: Although 93.7% of
      children could travel to any ED within 30 minutes, only 33.7% of children could
      travel to an ED with a WPRS of 100, 55.3% could travel to an ED with a WPRS at or
      above the 90th percentile, and 70.2% could travel to an ED with a WPRS at or
      above the 75th percentile. Among children within a 30-minute drive of an ED with
      the maximum WPRS, 90.9% lived closer to at least 1 alternative ED with a WPRS
      below the maximum. Access varied across census divisions, ranging from 14.9% of
      children in the East South Center to 56.2% in the Mid-Atlantic for EDs scoring a
      maximum WPRS. CONCLUSION: A significant proportion of US children do not have
      timely access to EDs with high pediatric readiness.

PMID- 29336801
TI  - Fixing nature's mistakes on the aortic valve: Will the normal form ensure normal
      function in the long term?

PMID- 29336802
TI  - Resection of pleural implants in patients with lung cancer should remain the
      exception rather than the rule.

PMID- 29336803
TI  - Postoperative cognitive dysfunction related to Alzheimer disease?

PMID- 29336804
TI  - Primum non nocere-it takes a village.

PMID- 29336805
TI  - Height supersedes weight: Height-diameter indexing keeps you ahead of the game.

PMID- 29336806
TI  - Variety is the spice of life: One-stage or two-stage repair of extensive chronic
      thoracic aortic dissection.

PMID- 29336807
TI  - Functionalized metal-organic framework nanocomposites for dispersive solid phase
      extraction and enantioselective capture of chiral drug intermediates.
AB  - The facile preparation, characterization and application of a novel magnetic
      graphene oxide- metal organic framework [Zn2(d-Cam)2(4, 4'-bpy)]n (MGO-ZnCB) as a
      sorbent for fast, simple and enantioselective capture of chiral drug
      intermediates are presented in this paper. The MGO-ZnCB nanocomposite, developed
      by encapsulating MGO nanoparticles into the homochiral metal organic framework of
      ZnCB, can integrate the advantages from each component endowing the hybrids with
      improved synergystic effects. The enantioselective performance of MGO-ZnCB was
      evaluated by dispersive magnetic nanoparticle solid phase extraction (d-MNSPE) of
      1, 1'-bi-2-naphthol (BN) and 2, 2'-furoin (Furoin) racemic solutions. Due to the
      excellent dispersive capability, high stability, relatively larger saturation
      magnetization and distinct enrichment capacity of MGO-ZnCB, the d-MNSPE method
      provids good enantioselective separation of these compounds with enantiomeric
      excess (ee) values as high as 74.8% and 57.4%, respectively. The entire process
      with BN or Furoin can be completed within 3 min or less. After washing with
      methanol, the host MGO-ZnCB can be easily recycled and reused six times without
      any apparent loss of performance. Furthermore, the adsorbed BN and Furoin in
      nanodomains of the MGO-ZnCB composite were directly investigated for the first
      time by atomic force microscopy-infrared (AFM-IR) technique.

PMID- 29336808
TI  - Miniaturized solid-phase extraction of macrolide antibiotics in honey and bovine
      milk using mesoporous MCM-41 silica as sorbent.
AB  - A simple and effective method of miniaturized solid-phase extraction (mini-SPE)
      was developed for the simultaneous purification and enrichment of macrolide
      antibiotics (MACs) (i.e. azithromycin, clarithromycin, erythromycin, lincomycin
      and roxithromycin) from honey and skim milk. Mesoporous MCM-41 silica was
      synthesized and used as sorbent in mini-SPE. Several key parameters affecting the
      performance of mini-SPE procedure were thoroughly investigated, including sorbent
      materials, amount of sorbent and elution solvents. Under the optimized condition,
      satisfactory linearity (r2 > 0.99), acceptable precision (RSDs, 0.3-7.1%), high
      sensitivity (limit of detection in the range of 0.01-0.76 MUg/kg), and good
      recoveries (83.21-105.34%) were obtained. With distinct advantages of simplicity,
      reliability and minimal sample requirement, the proposed mini-SPE procedure
      coupled with ultrahigh performance liquid chromatography and quadrupole time-of
      flight tandem mass spectrometry could become an alternative tool to analyze the
      residues of MACs in complex food matrixes.

PMID- 29336809
TI  - Screening of break point cluster region Abelson tyrosine kinase inhibitors by
      capillary electrophoresis.
AB  - In the present study, a capillary electrophoresis (CE) method was developed for
      screening of inhibitors against the break point cluster region Abelson tyrosine
      kinase (BCR-ABL). The screening method was established by using 5
      carboxyfluorescein labeled peptide substrate of BCR-ABL (F-ABLS), a known BCR-ABL
      tyrosine kinase inhibitor dasatinib, as well as a small chemical library
      consisting of 37 natural products. Thus, the inhibition of BCL-ABL kinase by
      small inhibitors was assayed by a CE system equipped with the laser induced
      fluorescence detector. The yield of phosphorylated product could be precisely
      measured through the separation by CE. The method is competent for enzymatic
      inhibition assay as well as the measurement of the inhibition kinetics. For
      screening BCR-ABL tyrosine kinase inhibitors, the hits were readily identified
      once the peak area of the phosphorylated products was reduced in comparison with
      the negative control. By taking the advantage of the screening method, luteolin
      and epicatechin gallate were discovered as the new BCR-ABL inhibitors.

PMID- 29336811
TI  - Discussion.

PMID- 29336810
TI  - Does adjuvant radiation provide any survival benefit after an R1 resections for
      pancreatic cancer?
AB  - BACKGROUND: The benefit of adding external beam radiation to adjuvant
      chemotherapy in patients that have undergone a margin positive resection for
      early stage, pancreatic ductal adenocarcinoma has not been determined
      definitively. METHODS: The National Cancer Data Base was queried to evaluate the
      utility of adjuvant radiation in patients with pathologic stage I-II pancreatic
      ductal adenocarcinoma who underwent upfront pancreatoduodenectomy with a positive
      margin (margin positive resection) between 2004 and 2013. RESULTS: In the study,
      1,392 patients met inclusion criteria, of whom 263 (18.9%) were lymph node
      negative (pathologic stages IA, IB, IIA) and 1,129 (81.1%) were node-positive
      (pathologic stage IIB); 938 (67.4%) patients received adjuvant radiation and
      chemotherapy, while 454 (32.6%) received adjuvant chemotherapy alone. Cox
      modeling stratified by nodal status demonstrated the benefit of radiation to be
      statistically significant only in node positive patients (hazard ratio 0.81, 95%
      confidence interval, 0.71-0.93). Node-positive patients receiving adjuvant
      radiation and chemotherapy had an adjusted median survival of 17.5 months vs 15.2
      months for those receiving adjuvant chemotherapy alone (P=.003). In patients who
      had negative nodes, there was no difference in overall survival with radiation
      (22.5 vs 23.6 months, P=.511). CONCLUSION: Addition of radiation to adjuvant
      chemotherapy after a margin positive resection confers a survival benefit albeit
      limited (about 2 months) in patients with node-positive pancreatic head cancer.
      (Surgery 2017;160:XXX-XXX.).

PMID- 29336812
TI  - Enhancing surgical performance by adopting expert musicians' practice and
      performance strategies.
AB  - BACKGROUND: Surgery is a performing art-each surgical procedure is a live
      performance that has immediate and irreversible consequences for both the
      performer and the audience. Surgeons operate with surgical instruments, whereas
      musicians perform with musical instruments. Both perform in high-stress, high
      risk work environments, where small errors in motor performance or judgment can
      have immediate negative consequences. While there is abundant literature on
      musical performance and their impact on outcome, little similar research has been
      published in the field of surgery. We aimed at identifying expert musicians'
      practice and performance strategies that may aid surgeons to enhance their
      surgical performance. METHODS: In the study, 82 relevant English-language
      articles from 1974 to 2017 matched applicable search terms. Nominal Group
      Technique was applied to identify 5 key domains that comprise important parallels
      between surgical and expert musical performance. RESULTS: The 5 key domains
      identified were: (1) extensive training and deliberate practice, (2) dexterity
      and ambidexterity, (3) performance evaluation and competition, (4) performance
      related injuries, and (5) performance anxiety. We found focused and mindful
      training in motor performance, not performing immediately after a hiatus from
      practice, training to improve the precision and responsiveness of the nondominant
      hand, continuous and critical self-evaluation, training in injury recognition and
      prevention, and pharmacologic factors to be of utmost importance. CONCLUSION:
      Critical parallels exist between surgical and expert musical performance that may
      improve surgical outcomes by adopting musicians' strategies for combating
      physiological and psychologic performance-related issues. Raising surgeons'
      awareness for this subject content may improve surgical performance and patient
      outcomes, as well as help prevent occupational injuries.

PMID- 29336813
TI  - Recurrence after curative-intent resection of perihilar cholangiocarcinoma:
      analysis of a large cohort with a close postoperative follow-up approach.
AB  - BACKGROUND: Although several studies have been conducted on the patterns of
      recurrence in resected perihilar cholangiocarcinoma, they have many limitations.
      The aim of this study was to investigate recurrence after resection and to
      evaluate prognostic factors on the time to recurrence and recurrence-free
      survival. METHODS: Consecutive patients who underwent curative-intent resection
      of perihilar cholangiocarcinoma between 2001 and 2012 were reviewed
      retrospectively. The Cox proportional hazards model was used for multivariable
      analysis. RESULTS: In the study period, 402 patients underwent resection of
      perihilar cholangiocarcinoma (R0, n = 340; R1, n = 62). Radial margin positivity
      (n = 43, 69%) was the most common reason for R1 resection. The median follow-up
      of survivors was 7.4 years. The cumulative recurrence probability was higher in
      R1 than in R0 resection (86% vs 57% at 5 years, P < .001). Seventeen R0 patients
      had a recurrence over 5 years after resection. There was no difference in median
      survival time after recurrence between R0 and R1 resection (10 vs 7 months). The
      proportion of isolated locoregional recurrence was higher in R1 than in R0
      resection (37% vs 16%, P < .001), whereas the proportion of distant recurrence
      was similar. In R0 resection, the independent prognostic factors for time to
      recurrence and recurrence-free survival were microscopic venous invasion and
      lymph node metastasis. CONCLUSION: More than half of patients with perihilar
      cholangiocarcinoma experience recurrence after R0 resection. These recurrences
      occur frequently within 5 years but occasionally after 5 years, which emphasizes
      the need for close and long-term surveillance. Adjuvant strategies should be
      considered, especially for patients with nodal metastasis or venous invasion even
      after R0 resection.

PMID- 29336814
TI  - Inhibition of Interleukin-10 in the tumor microenvironment can restore mesothelin
      chimeric antigen receptor T cell activity in pancreatic cancer in vitro.
AB  - BACKGROUND: Pancreatic cancer cells are known to shield themselves from
      immunosurveillance by secreting immune inhibitory cytokines such as Interleukin
      10. Using mesothelin, a differentiating antigen that is overexpressed in
      pancreatic cancer, we assessed the negative effect of the tumor microenvironment
      on chimeric antigen receptor T cell-based immunotherapy and its reversal via
      depletion of Interleukin-10. METHODS: T cells cultured in pancreatic cancer-cell
      conditioned medium were transduced with lentiviruses encoding mesothelin-chimeric
      antigen receptor in the presence or absence of anti-Interleukin-10-blocking
      antibody. RESULTS: Coculture supernatants of conditioned medium displayed
      significant inhibition of interferon gamma and granzyme B secretion, both of
      which are crucial for induction of target cell cytotoxicity. In contrast, this
      inhibition was restored toward baseline when conditioned medium was Interleukin
      10- depleted (p < .05 for both interferon gamma and granzyme B). In addition, we
      observed a significant decrease in mesothelin-chimeric antigen receptor T cell
      induced cytotoxicity of BxPC-3 target cells in the presence of conditioned
      medium. Furthermore, we observed a partial blunting of this inhibition when
      Interleukin-10 was depleted from the conditioned medium. CONCLUSION: Substantial
      reversal of tumor-derived immunosuppression may be achieved by blocking
      Interleukin-10 in the local microenvironment, allowing for more effective
      cytotoxicity of mesothelin-engrafted chimeric antigen receptor T cells and
      enhancing the potential for clinical application.

PMID- 29336815
TI  - Impact of restricted intraoperative fluid infusion on liver dysfunction after
      portal venous embolization protocols for major hepatectomy.

PMID- 29336816
TI  - Traumatic thoracic rib cage hernias: Operative management and proposal for a new
      anatomic-based grading system.
AB  - BACKGROUND: Traumatic Rib Cage Hernias (TRCH) requiring operative repair are rare
      and there is currently no literature to guiding surgical management. METHODS:
      Perioperative review of TRCH over 32 years. Five operative grades were developed
      based on extent of tissue/bone damage, size, and location. RESULTS: Twenty-four
      patients (20 blunt, 4 penetrating) underwent operative repair. Lung was the
      herniated organ in 88% with a median of 4 rib fractures and average size of 60.25
      cm. Types of operation were well clustered by assigned TRCH grade. The majority
      required mesh (75%) and/or rib plating (79%). Complex tissue flap reconstruction
      was required in 10%. Full range-of-motion was maintained in 88% with79% returning
      to pre-injury activity levels. Five patients had continued pain at final follow
      up (mean = 7months). CONCLUSION: The size and degree of injury has important
      implications in the optimal surgical management of TRCHs. These operative grades
      effectively direct surgical care for these rare and complex injuries.

PMID- 29336817
TI  - Neurocognitive assessment in patients with a minor traumatic brain injury and an
      abnormal initial CT scan: Can cognitive evaluation assist in identifying patients
      who require surveillance CT brain imaging?
AB  - BACKGROUND: Evidence for repeat computed tomography (CT) in minor traumatic brain
      injury (mTBI) patients with intracranial pathology is scarce. The aim of this
      study was to investigate the utility of clinical cognitive assessment (COG) in
      defining the need for repeat imaging. METHODS: COG performance was compared with
      findings on subsequent CT, and need for neurosurgery in mTBI patients (GCS 13-15
      and positive CT findings). RESULTS: Of 152 patients, 65.8% received a COG (53.0%
      passed). Patients with passed COG underwent fewer repeat CT (43.4% vs. 78.7%; p =
      .001) and had shorter LOS (8.7 vs. 19.5; p < .05). Only 1 patient required
      neurosurgery after a passed COG. The negative predictive value of a normal COG
      was 90.6% (95%CI = 81.8%-95.4%). CONCLUSION: mTBI patients with an abnormal index
      CT who pass COG are less likely to undergo repeat CT head, and rarely require
      neurosurgery. The COG warrants further investigation to determine its role in
      omitting repeat head CT.

PMID- 29336818
TI  - Discussion of "Breast cancer in women under 50: Most are not high risk".

PMID- 29336819
TI  - Identification of a Corticohabenular Circuit Regulating Socially Directed
      Behavior.
AB  - BACKGROUND: The prefrontal cortex (PFC) has been implicated in the
      pathophysiology of social dysfunction, but the specific circuit partners
      mediating PFC function in health and disease are unclear. METHODS: The excitatory
      designer receptor exclusively activated by designer drugs (DREADD) hM3Dq was used
      to induce PFC activation during social behavior measured in the three-chamber
      sociability assay (rats/mice). Functional magnetic resonance imaging was combined
      with hM3Dq-mediated PFC activation to identify novel nodes in the "social brain"
      in a hypothesis-free manner. In multiplexed DREADD experiments, hM3Dq and the
      inhibitory KORDi were used to bidirectionally modulate PFC activity and measure
      social behavior and global functional magnetic resonance imaging signature. To
      characterize the functional role of specific nodes identified in this functional
      magnetic resonance imaging screen, we used anterograde and retrograde tracers,
      optogenetic and DREADD-assisted circuit mapping, and circuit behavioral
      experiments. RESULTS: PFC activation suppressed social behavior and modulated
      activity in a number of regions involved in emotional behavior. Bidirectional
      modulation of PFC activity further refined this subset of brain regions and
      identified the habenula as a node robustly correlated with PFC activity.
      Furthermore, we showed that the lateral habenula (LHb) receives direct synaptic
      input from the PFC and that activation of LHb neurons or the PFC inputs to the
      LHb suppresses social preference. Finally, we demonstrated that LHb inhibition
      can prevent the social deficits induced by PFC activation. CONCLUSIONS: The LHb
      is thought to provide reward-related contextual information to the mesolimbic
      reward system known to be involved in social behavior. Thus, PFC projections to
      the LHb may represent an important part of descending PFC pathways that control
      social behavior.

PMID- 29336820
TI  - Micro-CT and micro-FE analysis of pedicle screw fixation under different loading
      conditions.
AB  - Anchorage of pedicle screw instrumentation in the elderly spine with poor bone
      quality remains challenging. In this study, micro finite element (uFE) models
      were used to assess the specific influence of screw design and the relative
      contribution of local bone density to fixation mechanics. These were created from
      micro computer tomography (uCT) scans of vertebras implanted with two types of
      pedicle screws, including a full region-or-interest of 10 mm radius around each
      screw, as well as submodels for the pedicle and inner trabecular bone of the
      vertebral body. The local bone volume fraction (BV/TV) calculated from the uCT
      scans around different regions of the screw (pedicle, inner trabecular region of
      the vertebral body) were then related to the predicted stiffness in simulated
      pull-out tests as well as to the experimental pull-out and torsional fixation
      properties mechanically measured on the corresponding specimens. Results show
      that predicted stiffness correlated excellently with experimental pull-out
      strength (R2 > 0.92, p < .043), better than regional BV/TV alone (R2 = 0.79, p =
      .003). They also show that correlations between fixation properties and BV/TV
      were increased when accounting only for the pedicle zone (R2 = 0.66-0.94, p <= 
      .032), but with weaker correlations for torsional loads (R2 < 0.10). Our analyses
      highlight the role of local density in the pedicle zone on the fixation stiffness
      and strength of pedicle screws when pull-out loads are involved, but that local
      apparent bone density alone may not be sufficient to explain resistance in
      torsion.

PMID- 29336821
TI  - Validation of radiostereometric analysis in six degrees of freedom for use with
      reverse total shoulder arthroplasty.
AB  - A phantom study was conducted to determine bias in motion and bias at zero motion
      of radiostereometric analysis (RSA) for evaluating implant relative displacement
      in reverse total shoulder arthroplasty (RTSA). A Sawbones shoulder phantom was
      fitted with a RTSA implant set and 13 tantalum markers. The model was fixed to a
      manual micrometer, providing controlled movements though fifteen known increments
      in translation and twelve increments in rotation (0.02-5.00 mm and 0.1-6.0
      degrees ), along each translation and rotation axis. Movement between the glenoid
      and humerus was assessed using beads vs. beads (B/B), model vs. beads (M/B), and
      model vs. model (M/M) measurement methods in a model-based RSA environment. Bias
      in motion and bias at zero motion were defined as the difference between measured
      and accepted reference values, and the difference between double examinations
      with a theoretical displacement of zero, respectively. Bias in motion ranged from
      0.054 +/- 0.010 to 0.129 +/- 0.014 mm and 0.076 +/- 0.025 to 0.126 +/- 0.025
      degrees  (B/B), 0.023 +/- 0.009 to 0.126 +/- 0.016 mm and 0.111 +/- 0.033 to
      0.794 +/- 0.251 degrees  (M/B), and 0.029 +/- 0.010 to 0.135 +/- 0.030 mm and
      0.243 +/- 0.088 to 0.384 +/- 0.153 degrees  (M/M). Bias at zero motion ranged
      from 0.120 to 0.156 mm and 0.075 to 0.206 degrees  (B/B), 0.074 to 0.149 mm and
      0.067 to 1.953 degrees  (M/B), and 0.069 to 0.259 mm and 0.284 to 1.273 degrees 
      (M/M). This is the first RSA for RTSA study, with results comparable to those
      validating the use of RSA for hip and knee arthroplasties (accepted as 0.05-0.50
      mm and 0.15-1.15 degrees ), justifying the potential use of RSA as a tool for
      measuring implant displacement in the shoulder.

PMID- 29336822
TI  - Role of Color Doppler Ultrasound in the Diagnosis of Idiopathic Facial Aseptic
      Granuloma.

PMID- 29336823
TI  - A reliable and easy to transport quality control method for chlamydia and
      gonorrhoea molecular point of care testing.
AB  - Quality control (QC) is an essential component of point-of-care testing programs.
      In the context of a randomised-controlled trial (TTANGO) using GeneXpert (Xpert)
      Chlamydia trachomatis and Neisseria gonorrhoeae (CT/NG) point-of-care testing in
      remote areas of Australia, we aimed to develop and utilise a stable positive
      control material. Bacterial cultures of CT and NG were resuspended together to
      provide cycle threshold (Ct) values of approximately 25 cycles for both CT and NG
      when tested on the Xpert CT/NG assay. These positive control suspensions were
      dried in aliquots, heat inactivated, and then provided to 12 participating health
      services as research-only QC samples in kit form. At each service, a QC sample
      was resuspended and tested each month on the Xpert. QC results, including Xpert
      Ct values, were analysed from each site over 30 months and we calculated costs
      per QC sample. Overall, at 12 health services there were 89 QC samples tested
      (average of 8 tests per site per year). Mean Ct values for the 89 controls
      samples were 25.25 cycles (SD = 1.15) for CT, 24.04 cycles (SD = 1.400) for one
      NG target and 23.35 cycles (SD = 1.55) for the other NG target. No significant
      differences in Ct value for CT or NG controls were observed over a trial period
      of 30 months. Positive QC samples for research use in a trial of a molecular
      point-of-care assay were inexpensive to produce and stable when stored at 2-8
      degrees C. For routine use, additional requirements such as meeting National
      Association of Testing Authority (NATA) regulations and Therapeutic Goods
      Administration (TGA) approval will need to be achieved.

PMID- 29336824
TI  - Trait-based characterization of species transported on Japanese tsunami marine
      debris: Effect of prior invasion history on trait distribution.
AB  - Nearly 300 coastal marine species collected from >630 debris items from the 2011
      Great East Japan earthquake and tsunami have landed alive along the North
      American Pacific coast and the Hawaiian Archipelago. We synthesized life history,
      environmental, and distributional traits for 103 of these species and compared
      species with (n=30) and without (n=62) known invasion histories. The species
      represent 12 phyla, and Mollusca, Crustacea, and Bryozoa accounted for 71 of the
      103 species. The majority are native to the Northwest Pacific and the Central
      Indo-Pacific. Species with known invasion history were more common on artificial
      and hardpan substrates, in temperate reef, fouling, and flotsam habitats, at
      subtropical and tropical temperatures, and exhibited greater salinity tolerance
      than species with no prior invasion history. Thirty-five Japanese tsunami marine
      species without prior invasion history overlapped in ordination trait space with
      known invaders, indicating a subset of species in this novel assemblage that
      possess traits similar to species with known invasion history.

PMID- 29336825
TI  - Detecting the occurrence of indigenous and non-indigenous megafauna through
      fishermen knowledge: A complementary tool to coastal and port surveys.
AB  - Marine bioinvasions and other rapid biodiversity changes require today
      integrating existing monitoring tools with other complementary detection
      strategies to provide a more efficient management. Here we explored the efficacy
      of fishermen observations and traditional port surveys to effectively track the
      occurrence of both indigenous and non-indigenous megafauna in the Adriatic Sea.
      This consisted mainly of mobile taxa such as fishes, crustaceans and molluscs.
      Port surveys using traps and nets within 10 major Adriatic harbours, were
      compared with the information obtained from 153 interviews with local fishermen.
      Information gathered by traps and nets varied significantly and generally
      resulted of limited efficacy in exotic species detection. Interviews allowed
      tracking the occurrence of new species through time and space, providing
      complementary knowledge at the low cost. This combined approach improves our
      capability of being informed on the arrival of species of different origin,
      providing a more rational, improved basis for environmental management and
      decision making.

PMID- 29336827
TI  - Significant changes in CMS pharmacy services F-Tags for long-term care
      facilities.

PMID- 29336828
TI  - What is new in the world of immunizations for 2018.

PMID- 29336829
TI  - What don't we know about bladder control and why does it matter? An AGS-NIA
      collaborative conference sought answers - and progress.

PMID- 29336830
TI  - Interdisciplinary development and implementation of a dementia skills training
      program in a VA community living center: a pilot study.
AB  - This pilot study investigates the usefulness of a dementia care training program
      developed by an interdisciplinary team to address problem behaviors associated
      with dementia. Staff members of a VA Community Living Center completed an 8-hour
      workshop covering fundamental knowledge about dementia and instruction in skills
      to use with patients through video, lecture, and role-plays. Measures on dementia
      knowledge and perceived self-efficacy were completed by staff members before and
      after the workshop. Results revealed increases in self-efficacy and knowledge,
      with particular gains in general knowledge of dementia and communicating with
      patients. Younger staff members scored higher on tests of knowledge at pre- and
      post-test, whereas staff members with more years of work experience rated their
      self-efficacy higher at post-test only. There was an associated decrease in
      assaultive behaviors by patients with dementia in the year this workshop was
      implemented. Results highlight the benefit of interdisciplinary collaboration in
      developing educational content and the value of providing staff training on
      managing dementia-related behaviors. Adjustments to this training program are
      discussed.

PMID- 29336831
TI  - Ultraviolet radiation significantly enhances the molecular response to dispersant
      and sweet crude oil exposure in Nematostella vectensis.
AB  - Estuarine organisms are subjected to combinations of anthropogenic and natural
      stressors, which together can reduce an organisms' ability to respond to either
      stress or can potentiate or synergize the cellular impacts for individual
      stressors. Nematostella vectensis (starlet sea anemone) is a useful model for
      investigating novel and evolutionarily conserved cellular and molecular responses
      to environmental stress. Using RNA-seq, we assessed global changes in gene
      expression in Nematostella in response to dispersant and/or sweet crude oil
      exposure alone or combined with ultraviolet radiation (UV). A total of 110
      transcripts were differentially expressed by dispersant and/or crude oil
      exposure, primarily dominated by the down-regulation of 74 unique transcripts in
      the dispersant treatment. In contrast, UV exposure alone or combined with
      dispersant and/or oil resulted in the differential expression of 1133
      transcripts, of which 436 were shared between all four treatment combinations.
      Most significant was the differential expression of 531 transcripts unique to one
      or more of the combined UV/chemical exposures. Main categories of genes affected
      by one or more of the treatments included enzymes involved in xenobiotic
      metabolism and transport, DNA repair enzymes, and general stress response genes
      conserved among vertebrates and invertebrates. However, the most interesting
      observation was the induction of several transcripts indicating de novo synthesis
      of mycosporine-like amino acids and other novel cellular antioxidants. Together,
      our data suggest that the toxicity of oil and/or dispersant and the complexity of
      the molecular response are significantly enhanced by UV exposure, which may co
      occur for shallow water species like Nematostella.

PMID- 29336832
TI  - Anticoagulation in neonatal ECMO.
AB  - Despite advances made in technology and neonatal intensive care, the rate of
      hemorrhagic and thrombotic complications remains unacceptably high in patients
      undergoing extracorporeal membrane oxygenation (ECMO) and these complications
      negatively impact morbidity and mortality. Management of anticoagulation in
      neonates who have a developing hemostatic system is vastly different from adults
      and poses unique challenges. Variation in practice among ECMO centers regarding
      anticoagulation monitoring and titration reflects the lack of high-quality
      evidence. Novel anticoagulants may offer alternative options, though their impact
      on outcomes is yet to be demonstrated. In this chapter, we review the hemostatic
      alterations that occur during ECMO with a focus on current approaches and
      limitations to anticoagulation titration in neonates on ECMO.

PMID- 29336833
TI  - Education for ECMO providers: Using education science to bridge the gap between
      clinical and educational expertise.
AB  - A well-organized educational curriculum for the training of both novice and
      experienced ECMO providers is critical for the continued function of an
      institutional ECMO program. ELSO provides guidance for the education for ECMO
      specialists, physicians and staff, which incorporates "traditional" instructor
      centered educational methods, such as didactic lectures and technical skill
      training. Novel research suggests utilization of strategies that align with
      principles of adult learning to promote active learner involvement and reflection
      on how the material can be applied to understand existing and new constructs may
      be more effective. Some examples include the "flipped classroom," e-learning,
      simulation, and interprofessional education. These methodologies have been shown
      to improve active participation, which can be related to improvements in
      understanding and long-term retention. A novel framework for ECMO training is
      considered. Challenges in assessment and credentialing are also discussed.

PMID- 29336834
TI  - An overview of medical ECMO for neonates.
AB  - Extracorporeal membrane oxygenation (ECMO), a life-saving therapy for respiratory
      and cardiac failure, was first used in neonates in the 1970s. The indications and
      criteria for ECMO have changed over the years, but it continues to be an
      important option for those who have failed other medical therapies. Since the
      Extracorporeal Life Support Organization (ELSO) Registry was established in 1989,
      more than 29,900 neonates have been placed on ECMO for respiratory failure, with
      84% surviving their ECMO course, and 73% surviving to discharge or transfer. In
      this chapter, we will review the basics of ECMO, patient characteristics and
      criteria, patient management, ECMO complications, special uses of neonatal ECMO,
      and patient outcomes.

PMID- 29336836
TI  - Current status of tissue engineering applied to bladder reconstruction in humans.
AB  - CONTEXT AND OBJECTIVE: Bladder reconstruction is performed to replace or expand
      the bladder. The intestine is used in standard clinical practice for tissue in
      this procedure. The complications of bladder reconstruction range from those of
      intestinal resection to those resulting from the continuous contact of urine with
      tissue not prepared for this contact. In this article, we describe and classify
      the various biomaterials and cell cultures used in bladder tissue engineering and
      reviews the studies performed with humans. ACQUISITION OF EVIDENCE: We conducted
      a review of literature published in the PubMed database between 1950 and 2017,
      following the principles of the PRISM declaration. SYNTHESIS OF THE EVIDENCE:
      Numerous in vitro and animal model studies have been conducted, but only 18
      experiments have been performed with humans, with a total of 169 patients. The
      current evidence suggests that an acellular matrix, a synthetic polymer with
      urothelial and autologous smooth muscle cells attached in vitro or stem cells
      would be the most practical approach for experimental bladder reconstruction.
      CONCLUSIONS: Bladder replacement or expansion without using intestinal tissue is
      still a challenge, despite progress in the manufacture of biomaterials and the
      development of cell therapy. Well-designed studies with large numbers of patients
      and long follow-up times are needed to establish an effective clinical
      translation and standardisation of the check-up functional tests.

PMID- 29336835
TI  - Standard whole prostate gland radiotherapy with and without lesion boost in
      prostate cancer: Toxicity in the FLAME randomized controlled trial.
AB  - PURPOSE: To compare toxicity rates in patients with localized prostate cancer
      treated with standard fractionated external beam radiotherapy (EBRT) with or
      without an additional integrated boost to the macroscopically visible tumour.
      MATERIAL AND METHODS: FLAME is a phase 3 multicentre RCT (NCT01168479) of
      patients with pathologically confirmed localized intermediate or high-risk
      prostate cancer. The standard treatment arm (n = 287) received a dose to the
      entire prostate of 77 Gy in 35 fractions. The dose-escalated treatment arm (n =
      284) received 77 Gy in 35 fractions to the entire prostate, with an integrated
      boost up to 95 Gy to the multi-parametric MRI-defined (macroscopic) tumour within
      the prostate. Treatment related toxicity was measured using the CTCAE version
      3.0. Grade 2 or worse GU or GI events up to two years were compared between
      groups by presenting proportions and by Generalized Estimating Equations (GEE)
      analyses for repeated measures. RESULTS: Ninety percent of the 571 men randomly
      assigned between September 2009 and January 2015 had high-risk disease (Ash
      2000), of whom nearly 66% were prescribed hormonal therapy up to three years.
      Median follow-up was 55 months at the time of this analysis. Toxicity prevalence
      rates for both GI and GU increased until the end of treatment and regressed
      thereafter, with no obvious differences across treatment groups. Late cumulative
      GI toxicity rates were 11.1% and 10.2% for the standard and dose-escalated group,
      respectively. These rates were 22.6% and 27.1% for GU toxicity. GEE analyses
      showed that both GU toxicity and GI toxicity (>=grade 2) up to two years after
      treatment were similar between arms (OR 1.02 95%CI 0.78-1.33p = 0.81 and (OR 1.19
      95%CI 0.82-1.73p = 0.38), respectively. CONCLUSIONS: In intermediate- and high
      risk prostate cancer patients, focal dose escalation integrated with standard
      EBRT did not result in an increase in GU and GI toxicity when compared to the
      standard treatment up to two years after treatment. This suggests that the
      described focal dose escalation technique is safe and feasible.

PMID- 29336837
TI  - Effectiveness of definitive radiotherapy for squamous cell carcinoma of the vulva
      with gross inguinal lymphadenopathy.
AB  - OBJECTIVE: To evaluate the effectiveness and long-term side effects of definitive
      groin radiotherapy for vulvar cancer with grossly involved inguinal lymph nodes.
      METHODS: The records of 407 women with vulvar squamous cell carcinoma treated
      with radiotherapy at one institution during 1992-2014 were reviewed to identify
      patients who had radiographic or histologic evidence of grossly involved inguinal
      lymph nodes. Patients with lymphadenectomy before radiotherapy and patients
      treated for recurrent disease were excluded. Actuarial incidences of vulvar,
      inguinal, and distant recurrences, the relationship between vulvar recurrence and
      inguinal recurrence, and overall survival were analyzed using the Kaplan-Meier
      method. RESULTS: Thirty-three patients were identified. The median age at
      diagnosis was 64 years. The median long-axis radiographic diameter of the largest
      inguinal lymph node or lymph node mass was 2.5 cm (range, 1.4-8.7). Sixteen
      patients (48%) also had evidence of pelvic lymph node metastasis. The median
      radiation dose delivered to grossly involved nodes was 66.0 Gy (range, 60.0
      70.0). The 3-year actuarial incidences of vulvar, groin, and distant recurrences
      were 24.2%, 17.7%, and 30.3%, respectively. With a median follow-up time of 28
      months (range, 2-196), four patients (12%) had groin recurrence, of whom three
      also had vulvar recurrence. There were few major late adverse effects of regional
      radiotherapy. The 3-year overall survival rate was 51%. CONCLUSIONS: High-dose
      volume-directed radiotherapy achieves a high rate of local control with low risk
      of serious long-term toxic effects in patients with vulvar squamous cell
      carcinoma and grossly involved inguinal lymph nodes.

PMID- 29336838
TI  - Pediatric Concussion Update: What ED Nurses Should Know After "Humpty Dumpty"
      Falls.

PMID- 29336839
TI  - Effect of thymectomy on refractory autoimmune status epilepticus.
AB  - Refractory status epilepticus (RSE) is an increasingly recognized manifestation
      of autoimmune encephalitis, which can occur either as a paraneoplastic or non
      paraneoplastic disorder. The effect of tumor removal in paraneoplastic status
      epilepticus has never been explored systematically, although early tumor
      treatment is usually recommended. In this study, we report clinical, pathological
      and EEG findings of a patient who developed RSE as one of multiple paraneoplastic
      manifestations of thymoma and the effect of thymectomy on seizure outcome. To our
      knowledge, this is the first report of successful treatment of RSE with tumor
      removal in paraneoplastic encephalitis.

PMID- 29336841
TI  - Economic impact of the new oral treatments for multiple sclerosis.
AB  - INTRODUCTION: Multiple sclerosis (MS) is a chronic disease affecting the central
      nervous system and is characterised by inflammation, demyelination, gliosis, and
      axonal damage. The introduction of dimethyl fumarate and teriflunomide has led to
      an increase in the number of alternative first-line therapies for MS. The
      objective of this study was to evaluate the economic impact of the incorporation
      of new oral therapies at the reference unit (CSUR) at Hospital Universitario
      Puerta de Hierro Majadahonda. MATERIALS AND METHODS: We performed a retrospective
      observational study including patients diagnosed with MS, who underwent treatment
      with disease-modifying drugs in 2015 and were followed up for a minimum mean time
      of one year. Data were collected from patients' electronic clinical histories and
      the pharmacy service's programme for dispensing drugs to outpatients. RESULTS:
      Evaluating the cost of changing 125 patients' treatment from other drugs to
      dimethyl fumarate and teriflunomide, and comparing this with the cost that would
      have resulted from maintaining their previous treatment, demonstrated a total
      saving of ?169,107.31 over the study period. CONCLUSIONS: In addition to
      contributing new therapeutic alternatives, dimethyl fumarate and teriflunomide
      produced an economic saving in MS treatment at our hospital.

PMID- 29336840
TI  - Heterozygous TYROBP deletion (PLOSLFIN) is not a strong risk factor for cognitive
      impairment.
AB  - Biallelic loss-of-function mutations in TYROBP and TREM2 cause a rare disease
      that resembles early-onset frontotemporal dementia with bone lesions called
      polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy
      (PLOSL). Some PLOSL-causing variants in TREM2 have also been associated with
      Alzheimer's disease when heterozygous. Here, we studied the PLOSLFINTYROBP
      deletion that covers 4 of the gene's 5 exons. We genotyped 3220 older Finns (mean
      age 79, range 58-104) and found 11 deletion carriers (mean age 78, range 60-94).
      The carrier prevalence was 0.0034 (1 in 293) that matches previous findings in
      younger cohorts suggesting no significant early mortality. By comparing Mini
      Mental State Examination (MMSE) scores and diagnoses of dementia, we did not find
      any significant differences between TYROBP deletion carriers and noncarriers (all
      p-values >0.5). Neuropathological analysis of 2 deletion carriers (aged 89 and 94
      years) demonstrated only minimal beta amyloid pathology (Consortium to Establish
      a Registry for Alzheimer's Disease (CERAD) score 0). Collectively these results
      suggest that heterozygous carriership of the TYROBP deletion is not a major risk
      factor of cognitive impairment.

PMID- 29336842
TI  - Immunohistochemical localization of angiotensin AT1 receptors in the rat carotid
      body.
AB  - The carotid body (CB) is a major peripheral arterial chemoreceptor that initiates
      respiratory and cardiovascular adjustments to maintain homeostasis. Recent
      evidence suggests that circulating or locally produced hormones like angiotensin
      II acting via AT1 receptors modulate its activity in a paracrine-autocrine
      manner. The aim of this study was to examine the immunohistochemical localization
      of AT1 receptor in the CB of adult rats and to compare its expression in vehicle
      treated animals, and after the long-term application of its selective blocker
      losartan. Immunohistochemistry revealed that a subset of CB glomeruli and the
      vast majority of neurons in the adjacent superior cervical ganglion (SCG) were
      strongly AT1 receptor-immunoreactive. In the CB immunostaining was observed in
      the chemosensory glomus cells typically aggregated in cell clusters while the
      nerve fibers in-between and large capillaries around them were immunonegative.
      Exogenous administration of losartan for a prolonged time significantly reduces
      the intensity of AT1 receptor immunostaining in the CB glomus cells and SCG
      neurons. Our results show that AT1 receptors are largely expressed in the rat CB
      under physiological conditions, and their expression is down-regulated by
      losartan treatment.

PMID- 29336843
TI  - Neuroprotective effects of quercetin 4'-O-beta-d-diglucoside on human striatal
      precursor cells in nutrient deprivation condition.
AB  - Several investigations have demonstrated neuroprotective effects of quercetin, a
      polyphenol widely present in nature, against neurotoxic chemicals, as well as in
      neuronal injury/neurodegenerative disease models. Most of these studies have been
      performed with quercetin aglycone and its metabolites, while scanty data are
      available on its glycosides. This study is aimed at investigating the
      neuroprotective effects of quercetin 3,4'-O-beta-d-diglucoside (Q3,4'dG),
      isolated from the bulbs of the white cultivar (Allium cepa L.), using an in vitro
      model of human striatal precursor cells (HSPs), a primary culture isolated from
      the striatal primordium and previously characterized. To study the effect of
      Q3,4'dG on cell survival, HSPs were exposed to nutrient deprivation created by
      replacing culture medium with phosphate buffer saline (PBS). Our findings showed
      that Q3,4'dG treatment significantly promoted cell survival and strongly
      decreased apoptosis induced by nutrient deprivation, as evaluated by cell
      proliferation/death analyses. In addition, since the adhesive capacities of cells
      are essential for cell survival, the expression of some adhesion molecules, such
      as pancadherin and focal adhesion kinase, was evaluated. Interestingly, PBS
      exposure significantly decreased the expression of both molecules, while in the
      presence of Q3,4'dG this effect was prevented. This study provides evidence of a
      neuroprotective role exerted by Q3,4'dG and suggests its possible implication in
      sustaining neuronal survival for prevention and treatment of neurodegenerative
      disorders.

PMID- 29336844
TI  - Detecting and Avoiding Problems When Using the Cre-lox System.
AB  - The Cre-lox recombination approach is commonly used to generate cell-specific
      gene inactivation (or activation). We have noticed that the breeding and
      genotyping sections of papers utilizing Cre-lox techniques are frequently
      incomplete. While seemingly straightforward, there are important considerations
      that need to be implemented in the breeding and genotyping methods to prevent the
      introduction of experimental confounds. Germline recombination and transient
      expression of Cre recombinase during development are some examples of the
      complications that can occur, and conventional genotyping methods may fail to
      identify these events. In this opinion article, we highlight the importance of
      testing for unexpected recombination events, suggest strategies to isolate and
      minimize adverse recombination events, and encourage editors and reviewers to
      expect more definitive statements regarding the validation of genotyping.

PMID- 29336845
TI  - Defining B Cell Chromatin: Lessons from EBF1.
AB  - Hematopoiesis is regulated by signals from the microenvironment, transcription
      factor networks, and changes of the epigenetic landscape. Transcription factors
      interact with and shape chromatin to allow for lineage- and cell type-specific
      changes in gene expression. During B lymphopoiesis, epigenetic regulation is
      observed in multilineage progenitors in which a specific chromatin context is
      established, at the onset of the B cell differentiation when early B cell factor
      1 (EBF1) induces lineage-specific changes in chromatin, during V(D)J
      recombination and after antigen-driven activation of B cells and terminal
      differentiation. In this review, we discuss the epigenetic changes underlying B
      cell differentiation, focusing on the role of transcription factor EBF1 in B cell
      lineage priming.

PMID- 29336846
TI  - Sex Differences in Prevalence of Emergency Department Patient Substance Use.
AB  - PURPOSE: Substance use and misuse is prevalent in emergency department (ED)
      populations. While the prevalence of substance use and misuse is reported, sex
      specific trends in ED populations have not been documented. We set out to
      determine the sex-specific prevalence of ED patient substance use during this
      current epidemic. METHODS: A retrospective electronic data abstraction tool,
      developed for quality-improvement purposes, was used to assess ED visits in 3
      hospitals in northeastern Pennsylvania. All patients with ED diagnosis codes for
      substance use F10.000 through F 19.999 (excluding F17 codes for nicotine) were
      abstracted for network ED visits at all 3 hospitals. Data points included ED
      clinical enrollment site, primary substance used, sex, date of ED visit,
      disposition (including left without being seen, left against medical advice,
      discharged, admitted, and treatment in rehabilitation) for 18 months (January 1,
      2016 through July 31, 2017). The categorical parameters of sex, clinical
      enrollment site, diagnosis, date of ED visit, and disposition status were
      summarized as a proportion of the subject group. Time series analysis was used to
      assess trends in substance use and misuse visits by patient sex. FINDINGS: A
      total of 10,511 patients presented to the EDs during the study time period with a
      final diagnosis of a substance use-related reason and were included in the
      analysis. The mean age for these patients was 43.6 (SD 16.4) years, and the
      majority was male (65.6%, n = 6900). The most common substance in the final
      diagnosis for the ED visit was alcohol (54.3%; 95% CI, 53.3-55.2), followed by
      opioids (19.2%; 95% CI, 18.4-19.9) and cannabis (14.4%; 95% CI, 13.7-15.0).
      Females tended to be younger than males (42.4 years vs 44.3 years; P < 0.001),
      and were more likely to be discharged after the ED visit than males (36.1% vs
      32.3%; P < 0.001). When exploring differences in age by sex and substance, males
      with a final diagnosis including alcohol- and cannabis-related issues were older
      than females, whereas females diagnosed with opioid-related reasons were older
      than males (41.3 vs 38.9 years; P < 0.001). IMPLICATIONS: There are sex-specific
      differences in prevalence of patients presenting with substance use in the ED
      setting.

PMID- 29336847
TI  - Frequent contamination of nursing scrubs is associated with specific care
      activities.
AB  - BACKGROUND: The objective of this article is to assess health care worker (HCW)
      and patient care factors associated with bacterial contamination of scrubs.
      METHODS: We performed a cohort study of critical care HCWs. Participants were
      given 4 sets of new scrubs; each set was sampled 8 times during the 8-month study
      period on random days in the last 4 hours of the shift. Total colony counts and
      presence of prespecified pathogenic bacteria were assessed. Generalized
      estimating equation was used to identify factors associated with contamination.
      RESULTS: There were 720 samples obtained from 90 HCWs; 30% of samples were
      contaminated with pathogenic bacteria. Multivariate analysis showed that
      providing care for patients with wounds (odds ratio [OR], 1.75; 95% confidence
      interval [CI], 1.17-2.62; P < .01) or giving a bath (OR, 1.46; 95% CI, 0.96-2.22;
      P = .07) was associated with higher odds of scrub contamination. A second model
      showed the average log colony count of bacterial contamination of scrubs was
      higher when a bath was given (log colony count difference, 0.21; P = .05) but
      lower among HCWs assigned to care for at least 1 patient on contact precautions
      (log colony count difference, 0.28; P < .01). CONCLUSIONS: HCW attire was
      frequently contaminated with bacteria. Providing care for patients with wounds or
      giving a bath were associated with scrub contamination by pathogenic bacteria.
      However, the amount of contamination was lower among HCWs who were assigned to
      care for patients on contact precautions.

PMID- 29336848
TI  - Response to a letter to the Editor regarding the prospective evaluation of risk
      factors and clinical influence of carbapenem resistance in children with gram
      negative bacteria infection.

PMID- 29336849
TI  - "Let's not hurry, but let's not waste time": The importance of appropriate
      management of non-ST-elevation myocardial infarction.

PMID- 29336850
TI  - Microvenous Reflux in the Skin of Limbs with Superficial Venous Incompetence.
AB  - This study investigated whether microvenous reflux can be detected in limbs with
      chronic venous disease using superb microvascular imaging (SMI) and colour
      Doppler imaging. Participants with venous disease (limbs, n = 26) and without
      venous disease (limbs, n = 10) were studied. The skin in the medial gaiter region
      was imaged using both SMI and colour Doppler to identify reflux in the small
      vessels in response to distal augmentation. The diameters and depths of
      responsive vessels were measured. In limbs with venous disease, reflux in
      response to provocation was visualised with SMI in a greater number of vessels
      (12/26 versus 4/26) and smaller vessels than with colour Doppler. Reflux in the
      superficial skin veins was demonstrated in one control participant (1/10) using
      SMI and in none using colour Doppler (0/10). Our study indicates that microvenous
      reflux is demonstrable in limbs with venous disease and that SMI is more
      sensitive than colour Doppler.

PMID- 29336851
TI  - Clinical Utility of Fetal Short-Lag Spatial Coherence Imaging.
AB  - In this study, we evaluate the clinical utility of fetal short-lag spatial
      coherence (SLSC) imaging. Previous work has documented significant improvements
      in image quality with fetal SLSC imaging as quantified by measurements of
      contrast and contrast-to-noise ratio (CNR). The objective of this study was to
      examine whether this improved technical efficacy is indicative of the clinical
      utility of SLSC imaging. Eighteen healthy volunteers in their first and second
      trimesters of pregnancy were scanned using a modified Siemens SC2000 clinical
      scanner. Raw channel data were acquired for routinely examined fetal organs and
      used to generate fully matched raw and post-processed harmonic B-mode and SLSC
      image sequences, which were subsequently optimized for dynamic range and other
      imaging parameters by a blinded sonographer. Optimized videos were reviewed in
      matched B-mode and SLSC pairs by three blinded clinicians who scored each video
      based on overall quality, target conspicuity and border definition. SLSC imaging
      was highly favored over conventional imaging with SLSC scoring equal to (28.2 +/-
      10.5%) or higher than (63.9 +/- 12.9%) B-mode for video pairs across all examined
      structures and processing conditions. Multivariate modeling revealed that SLSC
      imaging is a significant predictor of improved image quality with p <= 0.002.
      Expert-user scores for image quality support the application of SLSC in fetal
      ultrasound imaging.

PMID- 29336852
TI  - Brazilian species of Calliandra Benth. (tribe Ingeae) are nodulated by diverse
      strains of Paraburkholderia.
AB  - The Chapada Diamantina in NE of Brazil is a biodiversity hotspot and a center of
      radiation for many Neotropical legume genera, such as Calliandra and Mimosa. The
      present study aimed to evaluate nodulation in Calliandra species endemic to
      various environments, and to characterize the diversity of their symbiotic
      rhizobia using housekeeping (16S rRNA, recA) and plasmid-borne, symbiosis-related
      (nifH and nodC) genes. The nodulation ability of selected isolates was assessed.
      All of the 126 bacterial isolates from 18 Calliandra species collected in six
      different vegetation types were identified as Paraburkholderia according to their
      housekeeping and symbiosis gene phylogenies. They were grouped in seven clades in
      relation to the dominant vegetation type in their native environments. The
      majority, particularly those from highland "campo rupestre" vegetation, were
      similar to Paraburkholderia nodosa, but had nodC genes identical to the Mimosa
      symbiont Paraburkholderia tuberum sv. mimosae. The other smaller groups were
      related to Paraburkholderia diazotrophica and Paraburkholderia sabiae, and some
      single strains were not close to any known species. The symbionts of Calliandra
      spp. in NE Brazil are Paraburkholderia strains closely-related to Mimosa
      symbionts from the same region. NE Brazil is a reservoir of symbiotic
      Paraburkholderia that have an affinity for genera in the Mimosoid clade.

PMID- 29336853
TI  - Updated Guidelines on Infection Prevention in Pediatric Ambulatory Settings.
AB  - The American Academy of Pediatrics (AAP) recently released updated guidelines on
      infection control and prevention in pediatric outpatient settings. Key
      recommendations include mandatory influenza vaccination for all healthcare
      workers offered free to all staff, expanded guidance on infection control
      practices for children with cystic fibrosis, guidance on additional prevention
      procedures during community outbreaks of infectious diseases and recommendations
      on improving communication between healthcare facilities when referring
      potentially contagious patients. The new guidelines modify standard precautions
      by indicating that gloves are not required for diaper changes or some body fluid
      contact (nasal secretions and tears) in a well child, or when administering
      vaccines. In addition, efforts should be made to minimize exposure to infections
      from contaminated toys that cannot be cleaned including plush toys, cleaning toys
      in waiting rooms each day and encouraging families to bring their own toys or
      books to visits.

PMID- 29336854
TI  - Morphologically-directed Raman spectroscopy for forensic soil analysis.
AB  - Morphologically-directed Raman spectroscopy (MDRS) is a novel yet reliable
      analytical technique that can be used for a variety of forensic applications,
      enabling scientists to gain more information from samples than they obtain using
      more traditional methods. In soil forensics, MDRS delivers particle size
      distribution and microscopic morphological characteristics for the particles
      present, and at the same time allows secure mineral identification. In this
      article, we explore the benefits of utilizing soil in forensic investigations,
      and demonstrate the value of applying MDRS. Two case studies illustrate the real
      life potential and applications of this technology.

PMID- 29336855
TI  - Update on Anemia in ESRD and Earlier Stages of CKD: Core Curriculum 2018.
AB  - Anemia is a frequent complication during the later stages of chronic kidney
      disease. When present, it may cause symptoms such as fatigue and shortness of
      breath. The pathogenesis of anemia in chronic kidney disease is complex, but a
      central feature is a relative deficit of erythropoietin. New information has
      elucidated the critical role of the hypoxia-sensing system in mediating
      erythropoietin synthesis and release. Iron deficiency is a second important
      factor in the anemia of chronic kidney disease. New insights into the dynamics of
      iron metabolism have clarified the role of chronic inflammation and hepcidin as
      key mediators of impaired iron utilization. In this article, we review the
      epidemiology, pathobiology, clinical evaluation, and treatment of anemia in
      chronic kidney disease.

PMID- 29336856
TI  - Evaluation of Kidney Donors: Core Curriculum 2018.
AB  - Nearly 100,000 patients are waiting for a kidney transplant, yet each year only
      11,000 undergo transplantation with a deceased donor kidney. Annual death rates
      among waitlist registrants range from 5% to 15%; many die before receiving a
      transplant. Not surprisingly, registrants turn to family and friends to become
      living kidney donors on their behalf. Living kidney donor selection practices aim
      to quantify lifetime risk for kidney failure based on a candidate's predonation
      demographic and health characteristics. It has been established that estimated
      lifetime risk for kidney failure varies considerably based on predonation
      comorbid conditions, and as such, it is of paramount importance that potential
      living donor candidates undergo proper medical, surgical, and psychosocial
      screening before donation. This installment of AJKD's Core Curriculum in
      Nephrology provides readers with the tools necessary for proper evaluation of
      living kidney donor candidates.

PMID- 29336857
TI  - Identifying Risk Factors for the Development of Stiffness After Revision Total
      Knee Arthroplasty.
AB  - BACKGROUND: Although there are several studies concerning manipulation under
      anesthesia (MUA) after primary total knee arthroplasty, there is a paucity of
      literature evaluating MUA after revision total knee arthroplasty (rTKA). The
      purpose of this study was to determine the incidence, timing, and risk factors
      associated with MUA after rTKA. METHODS: The Humana database was reviewed from
      2007 to 2015 for all patients who underwent rTKA. Patients who underwent rTKA
      followed by ipsilateral MUA were identified. Time to MUA was calculated monthly.
      Possible risk factors analyzed included preoperative narcotic use, smoking,
      anxiety and/or depression, diabetes, obesity, age, and sex. Multivariate logistic
      regression was used to determine odds ratio. RESULTS: In total, 5414 rTKAs were
      included in the study and 1.7% (n = 96) underwent MUA after surgery. Sixty-nine
      percent of MUAs occurred within the first 3 months after rTKA. Young patients
      (<50 years) had significantly higher odds of MUA after rTKA (6.5, P < .0001). No
      difference in odds of MUA (1.0, P = .85) occurred between males and females. A
      diagnosis of obesity, diabetes, anxiety and/or depression, previous history of
      narcotic use, or a history of smoking demonstrated no increased risk of MUA after
      rTKA. Multivariate logistic regression analysis demonstrated that younger age
      remained predictive of higher odds of MUA after rTKA. CONCLUSION: In this large
      multicenter cohort study, 1.7% of patients underwent MUA after rTKA and younger
      patients were 6 times more likely to have a MUA than patients over 50 years old.
      These data should serve to help counsel patients regarding their risk of MUA
      after rTKA.

PMID- 29336858
TI  - Are Ceramic Bearings Becoming Cost-Effective for All Patients?
AB  - BACKGROUND: The purpose of this study is to analyze whether the cost for ceramic
      on-polyethylene (C-PE) and ceramic-on-ceramic (COC) bearings used in primary
      total hip arthroplasty (THA) was changing over time, and if the cost differential
      between ceramic bearings and metal-on-polyethylene (M-PE) bearings was
      approaching the previously published tipping point for cost-effectiveness of
      $325. METHODS: A total of 245,077 elderly Medicare patients (65+) who underwent
      primary THA between 2010 and 2015 were identified from the United States Medicare
      100% national administrative hospital claims database. The inpatient hospital
      cost, calculated using cost-to-charge ratios, and hospital payment were analyzed.
      The differential cost of C-PE and COC bearings, compared to M-PE, were evaluated
      using parametric and nonparametric models. RESULTS: After adjustment for patient
      and clinical factors, and the year of surgery, the mean hospital cost and
      payments for primary THA with a C-PE or COC was within +/-1% of the cost for
      primary THA with M-PE bearings (P < .001). From the nonparametric analysis, the
      median hospital cost was $318-$360 more for C-PE and COC than M-PE. The
      differential in median Medicare payment for THA with ceramic bearings compared to
      M-PE was <$100. Cost differentials were found to decrease significantly over time
      (P < .001). CONCLUSION: Patient and clinical factors had a far greater impact on
      the cost of inpatient THA surgery than bearing selection. Because we found that
      costs and cost differentials for ceramic bearings were decreasing over time, and
      approaching the tipping point, it is likely that the cost-effectiveness
      thresholds relative to M-PE are likewise changing over time and should be
      revisited in light of this study.

PMID- 29336859
TI  - Effectiveness of chemotherapy counselling on self-esteem and psychological
      affects among cancer patients in Malaysia: Randomized controlled trial.
AB  - OBJECTIVES: The aim of this study was to implement and evaluate the outcomes of
      chemotherapy counselling based on the "Managing Patients on Chemotherapy" module
      on self-esteem and psychological affect (anxiety, depression) of cancer patients
      by pharmacists in ten selected government hospitals in Peninsular Malaysia.
      METHODS: A randomized control trial was conducted among 2120 cancer patients from
      April 2016 to January 2017 in ten selected government hospitals in Peninsular
      Malaysia. Cancer patients were randomly assigned to intervention and control
      groups. The intervention group received chemotherapy counselling by pharmacists
      based on the "Managing Patients on Chemotherapy" module. The outcomes were
      assessed at baseline, 1st, 2nd and 3rd follow-ups after counselling. In the
      course of data analysis; independent sample t-test, chi-square and two-way
      repeated measures ANOVA were conducted. RESULTS: Mean scores of self-esteem in
      the intervention group had significant difference in comparison with those of the
      control group in the 1st, 2nd and 3rd follow-ups after counselling (P < 0.0001).
      Also, among those with depression and anxiety at baseline, there was reduction in
      depression and anxiety scores after the 1st, 2nd and 3rd follow-ups after
      counselling (p < 0.05). CONCLUSION: Repetitive counselling by pharmacists based
      on the "Managing Patients on Chemotherapy" module had positive effect on
      improving self-esteem and psychological affect of cancer patients undergoing
      chemotherapy in Peninsular Malaysia. PRACTICE IMPLICATIONS: This module can be
      used for all Malaysian cancer patients undergoing chemotherapy to improving self
      esteem and psychological affect.

PMID- 29336860
TI  - Coaching to support men in making informed choices about prostate cancer
      screening: A qualitative study.
AB  - OBJECTIVE: The objective of this study was to examine the perceptions of men,
      practice nurses (PNs) and general practitioners (GPs) on patient decision
      coaching for prostate cancer screening. METHODS: Seven focus groups were
      conducted with 47 participants, representing three stakeholder groups - men, GPs
      and PNs. All focus group discussions were conducted by the same facilitator and
      guided by a semi-structured interview schedule. Transcriptions were analysed by
      thematic analysis. RESULTS: Knowledge about the merits of prostate cancer
      screening was high amongst GPs, but limited with PNs and men. All groups saw the
      value in PN-led decision coaching for men considering screening for prostate
      cancer, but had reservations about its implementation in practice. Barriers to
      implementing a decision coaching system with PNs included staffing and cost of
      implementation. CONCLUSION: GPs, PNs and men identified benefits for the use of a
      PN-led decision coaching support intervention to assist men with making an
      informed choice about screening for prostate cancer. Stakeholders had
      reservations about how a PN-led intervention would effectively work in clinical
      practice. PRACTICE IMPLICATIONS: A feasibility study is required to examine
      barriers and enablers to implementing a PN-led decision coaching process for
      prostate cancer screening in the Australian primary healthcare setting.

PMID- 29336861
TI  - Care guide use for repeated non-emergent complaints and its effect on emergency
      department visit frequency.

PMID- 29336862
TI  - Reconciling Supply and Demand for State and Local Public Health Staff in an Era
      of Retiring Baby Boomers.
AB  - INTRODUCTION: The purpose of this study is to reconcile public health workforce
      supply and demand data to understand whether the expected influx of public health
      graduates can meet turnover events. METHODS: Four large public health workforce
      data sources were analyzed to establish measures of workforce demand, voluntary
      separations, and workforce employees likely to retire at state and local health
      departments. Data were collected in 2014-2016 and analyzed in 2016 and 2017.
      Potential workforce supply (i.e., candidates with formal public health training)
      was assessed by analyzing data on public health graduates. Supply and demand data
      were reconciled to identify potential gaps in the public health workforce.
      RESULTS: At the state and local level, ?197,000 staff are employed in health
      departments. This is down more than 50,000 from 2008. In total, >=65,000 staff
      will leave their organizations during fiscal years 2016-2020, with <=100,000
      staff leaving if all planned retirements occur by 2020. During 2000-2015, more
      than 223,000 people received a formal public health degree at some level. More
      than 25,000 students will receive a public health degree at some level in each
      year through 2020. CONCLUSIONS: Demands for public health staff could possibly be
      met by the influx of graduates from schools and programs of public health.
      However, substantial implications exist for transferal of institutional knowledge
      and ability to recruit and retain the best staff to sufficiently meet demand.

PMID- 29336863
TI  - Age-associated expression of vitamin D receptor and vitamin D-metabolizing
      enzymes in the male reproductive tract and sperm of Hu sheep.
AB  - The cellular response to 1,25-dihydroxyvitamin D3 (Vit D3; biologically active
      form of Vitamin D) is complex and depends not only on Vitamin D receptor (VDR)
      expression but also on cellular uptake of circulating Vit D3 and the presence and
      activity of Vitamin D-metabolizing enzyme. This study evaluated the expression of
      VDR and Vitamin D-metabolizing enzymes in the ram reproductive tract at different
      developmental stages and in spermatozoa. Nearly all cell types in the testes and
      epithelial cells of the caput, corpus, and cauda expressed VDR, CYP27B1, and
      CYP24A1 proteins. The mRNA and protein expression of CYP2R1, CYP27A1, and CYP27B1
      in the testes and cauda increased significantly with increasing age (P < 0.05).
      However, epididymal VDR mRNA and protein expression showed no significant
      difference (P < 0.05) between adult (9- and 24-month-old) and prepubertal (3
      month-old) rams. Furthermore, VDR and CYP24A1 were mainly concentrated in the mid
      piece of ejaculated or cauda epididymis spermatozoa or both. Additionally, VDR
      and CYP27B1 mRNA and protein expression levels were significantly higher in
      ejaculated spermatozoa than in cauda epididymal spermatozoa (P < 0.05). Moreover,
      VDR and CYP24A1 expression was significantly higher in high-motility than in low
      motility spermatozoa (P < 0.05). The diverse expression patterns of VDR and
      Vitamin D-metabolizing enzymes in the ram reproductive tract at different
      developmental stages and spermatozoa suggest it plays a potential role in
      spermatogenesis.

PMID- 29336864
TI  - Biochemical characterization, stability, and pathogen safety of a new fibrinogen
      concentrate (fibryga(r)).
AB  - Fibryga(r) is a new lyophilized fibrinogen concentrate for intravenous use for
      the treatment of congenital fibrinogen deficiency. fibryga(r) is produced from
      pooled human plasma and the final product is characterized by high purity,
      integrity, and pathogen safety. Functional activity of fibrinogen was
      demonstrated by cross-linking studies and thromboelastometry; integrity of the
      fibrinogen molecule was demonstrated by size exclusion chromatography and the
      detection of only trace amounts of activation markers in the final product.
      Pathogen safety of fibryga(r) was proved by downscaling studies for the two
      dedicated pathogen inactivation/removal steps, i.e. solvent detergent treatment
      and nanofiltration. Fibryga(r) is stable for at least three years when stored at
      room temperature. In conclusion, the performed studies demonstrated that
      fibryga(r) meets the requirements for a state-of-the-art fibrinogen concentrate,
      such as a satisfactory activity profile combined with a favorable pathogen safety
      profile and stability.

PMID- 29336865
TI  - Continuous Hyperfractionated Accelerated Radiotherapy (CHART) for Non-small Cell
      Lung Cancer (NSCLC): 7 Years' Experience From Nine UK Centres.
AB  - AIM: Continuous hyperfractionated accelerated radiotherapy (CHART) remains an
      option to treat non-small cell lung cancer (NSCLC; NICE, 2011). We have
      previously published treatment outcomes from 1998-2003 across five UK centres.
      Here we update the UK CHART experience, reporting outcomes and toxicities for
      patients treated between 2003 and 2009. MATERIALS AND METHODS: UK CHART centres
      were invited to participate in a retrospective data analysis of NSCLC patients
      treated with CHART from 2003 to 2009. Nine (of 14) centres were able to submit
      their data into a standard database. The Kaplan-Meier method estimated survival
      and the Log-rank test analysed the significance. RESULTS: In total, 849 patients
      had CHART treatment, with a median age of 71 years (range 31-91), 534 (63%) were
      men, 55% had undergone positron emission tomography-computed tomography (PET-CT)
      and 26% had prior chemotherapy; 839 (99%) patients received all the prescribed
      treatment. The median overall survival was 22 months with 2 and 3 year survival
      of 47% and 32%, respectively. Statistically significant differences in survival
      were noted for stage IA versus IB (33.2 months versus 25 months; P = 0.032) and
      IIIA versus IIIB (20 months versus 16 months; P = 0.018). Response at 3 months
      and outcomes were significantly linked; complete response showing survival of 34
      months against 19 months, 15 months and 8 months for partial response, stable and
      progressive disease, respectively (P < 0.001). Age, gender, performance status,
      prior chemotherapy and PET-CT did not affect the survival outcomes. Treatment was
      well tolerated with <5% reporting >=grade 3 toxicity. CONCLUSION: In routine
      practice, CHART results for NSCLC remain encouraging and we have been able to
      show an improvement in survival compared with the original trial cohort. We have
      confirmed that CHART remains deliverable with low toxicity rates and we are
      taking a dose-escalated CHART regimen forward in a randomised phase II study of
      sequential chemoradiotherapy against other accelerated dose-escalated schedules.

PMID- 29336866
TI  - Regulatory mechanisms of collagen expression by interleukin-22 signaling in
      scleroderma fibroblasts.
AB  - BACKGROUND: Various cytokines have been indicated to be involved in the
      pathogenesis of systemic sclerosis (SSc). IL-22 is one of the member of IL-10
      cytokine family, and several studies have implicated IL-22 signaling in the
      pathogenesis of autoimmune diseases. OBJECTIVES: To clarify the role of IL-22 in
      the regulatory mechanism of ECM expression and to determine the contribution of
      IL-22 to the phenotype of SSc. METHODS: The effect of IL-22 on ECM expression in
      normal fibroblasts was determined by using PCR array, real-time PCR and
      immunoblotting. microRNA expression was evaluated by real-time PCR. The
      expression levels of IL-22 in the skin and sera were determined by using
      immunohistochemical staining and ELISA. RESULTS: IL-22 significantly increased
      the expression of type I collagen protein without changing its mRNA levels in
      cultured normal human dermal fibroblast. The expression of let-7a, one of the
      microRNAs which have negative effect on type I collagen expression, was
      significantly decreased by the treatment with IL-22 in dermal fibroblasts. There
      was no significant difference in the serum levels of IL-22 between SSc patients
      and control subjects. However, the expression of IL-22 was detected in the
      infiltrated lymphocytes in the SSc dermis, but not in normal dermis. IL-22
      receptors were expressed in both normal and SSc dermal fibroblasts to the similar
      extent. CONCLUSION: IL-22 expressed in infiltrated lymphocytes may stimulate the
      up-regulation of type I collagen protein in dermal fibroblasts via let-7a down
      regulation in SSc skin.

PMID- 29336867
TI  - Nevus-like lesions on the lip and the foot.

PMID- 29336868
TI  - The therapeutic potential of targeting the peripheral endocannabinoid/CB1
      receptor system.
AB  - Endocannabinoids (eCBs) are internal lipid mediators recognized by the
      cannabinoid-1 and -2 receptors (CB1R and CB2R, respectively), which also mediate
      the different physiological effects of marijuana. The endocannabinoid system,
      consisting of eCBs, their receptors, and the enzymes involved in their
      biosynthesis and degradation, is present in a vast number of peripheral organs.
      In this review we describe the role of the eCB/CB1R system in modulating the
      metabolism in several peripheral organs. We assess how eCBs, via activating the
      CB1R, contribute to obesity and regulate food intake. In addition, we describe
      their roles in modulating liver and kidney functions, as well as bone remodeling
      and mass. Special importance is given to emphasizing the efficacy of the recently
      developed peripherally restricted CB1R antagonists, which were pre-clinically
      tested in the management of energy homeostasis, and in ameliorating both obesity-
      and diabetes-induced metabolic complications.

PMID- 29336870
TI  - Trends in Singing Voice Research: An Innovative Approach.
AB  - OBJECTIVES: The objectives of this study were to trace and describe research
      patterns in singing voice, to compare the amount of published research over time,
      to identify journals that published most papers on "singing voice," and to
      establish the most frequent research topics. MATERIALS AND METHODS: The study
      uses qualitative and quantitative approaches through descriptive statistics, text
      mining, and clustering. The authors conducted a search to identify scientific
      papers. The titles and abstracts were analyzed regarding word frequency and
      relations between them, through hierarchical cluster analysis and co-occurrence
      networks. The frequency of journals was calculated, as well as the amount of
      papers across time. RESULTS: Since 1949, 754 papers were published and an
      increase was noticed. Even though 162 journals were identified by the authors,
      the Journal of Voice holds the majority of papers, in every analyzed period. An
      evolution of studied topics is described. Up to 2010, the main theme was
      professional singers, especially classical and opera interpreters. Since then,
      voice quality and the effects of training gathered more attention. CONCLUSIONS:
      The growing interest in singing has been conspicuous since the first indexed
      paper. However, it has been slightly slowing down. Until 2010, great importance
      was given to the voice quality of singers and their occupational demands.
      Acoustic analysis was widely used to study the effects of training. Since 2010,
      the concern with functionality is increasing, rather than the organic voice
      structures. Musical perception studies have been a trend, as well as the use of
      electroglottography.

PMID- 29336869
TI  - Long-term Average Spectra Analysis of Voice in Children With Cleft Palate.
AB  - OBJECTIVES: The purpose of this study was to survey the spectral characteristics
      and to compare, using an acoustic analyzer, the objective data obtained from
      patients with cleft palates with the objective data of normal children using long
      term average spectra (LTAS) analysis. METHODS: Participants were divided into a
      clinical group and a control group. All participants were asked to practice
      reading a sentence to become fluent. The duration of each recording was about 60
      seconds. All samples were subjected to acoustic analysis using Praat software.
      All recordings were analyzed acoustically using LTAS. RESULTS: In this study,
      there was no significant difference between the control group and the clinical
      group in the low-frequency region (boys: 0-2720 Hz; girls: 0-2240 Hz). LTAS
      measurements showed a great difference between the control group and the clinical
      group in the middle-frequency region (boys: 2720-4000 Hz; girls: 2240-4000 Hz).
      We also found that the energy distributed in the clinical group was lower than
      that of the control group in the high-frequency region (4000 Hz-8000 Hz) in both
      boys and girls. CONCLUSIONS: The results reveal a lack of flat region in the
      middle-frequency range in the clinical group (both boys and girls) in comparison
      with the control group. The results also reveal that there is no significant
      difference across the control group and the clinical group in the low-frequency
      region.

PMID- 29336871
TI  - Epigenetic regulation of the kappa opioid receptor gene by an insertion-deletion
      in the promoter region.
AB  - Preclinical and clinical studies have demonstrated that the kappa opioid receptor
      (KOR) regulates reward, hedonic tone and emotions. At therapeutic level, on-going
      clinical trials are assessing the potential of targeting the KOR for the
      management of depression, anxiety disorders and substance use disorders. However,
      genetic polymorphisms in the KOR gene that potentially contribute to its
      implication in these phenotypes have been poorly studied. Here we investigated an
      insertion-deletion in the promoter region of KOR (rs35566036), recently
      associated with alcohol addiction, in a cohort of depressed subjects who died by
      suicide, as well as psychiatrically healthy individuals. Focusing on 3 brain
      regions (anterior insula, anterior cingulate cortex, and mediodorsal thalamus),
      we characterized the functional impact of this structural variant on the
      expression and patterns of DNA methylation of the KOR gene, using qPCR and
      targeted Bisulfite-Sequencing, respectively. While there was no significant
      change in the expression of KOR as a function of the insertion-deletion, or as a
      function of disease status in any brain region, we found that this variant
      strongly determines DNA methylation in KOR promoter, leading to a significant
      decrease in methylation levels of 8 nearby CpG dinucleotides located
      approximately 500 base pairs upstream the transcription start site. In addition,
      our results suggest a possible association between the insertion-deletion and
      depression; however, this result should be tested in larger populations. In sum,
      in this study we uncovered an epigenetic mechanism potentially contributing to
      KOR dysfunction in carriers of the insertion-deletion.

PMID- 29336872
TI  - Abundance of ribosomal RNA gene copies in the genomes of schizophrenia patients.
AB  - OBJECTIVE: The ribosome is a critical component of the translation machinery. The
      key component of ribosomes is ribosomal RNA (rRNA). Dysregulation of rRNA
      biogenesis has been implicated in some human diseases. One of the factors
      affecting rRNA biogenesis is the ribosomal RNA genes (rDNA) copy number in the
      genome. The aim of this study was to examine the rDNA copy number (CN) variation
      in the genomes of patients with schizophrenia (SZ) compared to healthy controls
      (HC). METHODS: We evaluated rDNA CN in leukocytes of 179 subjects with SZ (108
      male/71 female) in comparison with 122 HC (60 male/62 female) using two
      techniques: qPCR and nonradioactive quantitative hybridization (NQH), which is
      based on the use of biotinylated rDNA probes. RESULTS: rDNA CN (NQH) and rDNA CN
      (qPCR) was higher in SZ patients than in controls (median 542 vs 384, p=10-25 and
      median 498 vs 370, p=10-12). NQH was experimentally proved to be less sensitive
      to severe DNA damage than qPCR. The more DNA damage, the higher the ratio R=CN
      (NQH)/CN (qPCR). 15% of the SZ patients had significantly higher rDNA damage
      degree than the HC. CONCLUSION: Genomes of some SZ patients contain more
      ribosomal genes than those of HC. The elevated ribosomal genes copy number in
      human genome can be one of the genetic factors of schizophrenia development. This
      hypothesis requires further experimental studies to be corroborated or disproved.

PMID- 29336874
TI  - Regioselectivity of thiouracil alkylation: Application to optimization of
      Darapladib synthesis.
AB  - Darapladib is one of the most potent Lp-PLA2 (Lipoprotein-associated
      phospholipase A2) inhibitor with an IC50 of 0.25 nM. We demonstrate that a
      crucial step of Darapladib synthesis was not correctly described in the
      literature, leading to the production of wrong regioisomers. Moreover we show
      that the inhibitory activity is directly linked to the position on N1 since
      compounds bearing alkylation on different sites have potentially less interaction
      within the active site of Lp-PLA2.

PMID- 29336873
TI  - Optimization of novel monobactams with activity against carbapenem-resistant
      Enterobacteriaceae - Identification of LYS228.
AB  - Metallo-beta-lactamases (MBLs), such as New Delhi metallo-beta-lactamase (NDM-1)
      have spread world-wide and present a serious threat. Expression of MBLs confers
      resistance in Gram-negative bacteria to all classes of beta-lactam antibiotics,
      with the exception of monobactams, which are intrinsically stable to MBLs.
      However, existing first generation monobactam drugs like aztreonam have limited
      clinical utility against MBL-expressing strains because they are impacted by
      serine beta-lactamases (SBLs), which are often co-expressed in clinical isolates.
      Here, we optimized novel monobactams for stability against SBLs, which led to the
      identification of LYS228 (compound 31). LYS228 is potent in the presence of all
      classes of beta-lactamases and shows potent activity against carbapenem-resistant
      isolates of Enterobacteriaceae (CRE).

PMID- 29336875
TI  - Systems pharmacology dissection of the anti-stroke mechanism for the Chinese
      traditional medicine Xing-Nao-Jing.
AB  - Xing-Nao-Jing (XNJ) is a well-known injection that has been extensively applied
      in clinical treatment of stroke in China. However, the underlying mechanism of
      clinical administration of XNJ in stroke remains unclear. In this study, a
      systems pharmacology strategy based on pharmacokinetic and pharmacodynamics data
      was applied to analyze the pharmacological effect of XNJ on stroke. Sixteen
      active compounds were filtered from XNJ through Drug-likeness (DL) and Brain
      blood-barrier (BBB) evaluations. Ninety-four potential targets of these active
      components were identified by SysDT and SEA. Biological process and pathway
      enrichment analyses of these targets demonstrated that XNJ exerted anti-stroke
      effects by biological processes and pathways, such as the response to oxidative
      stress, regulation of blood pressure, calcium signaling pathway, and apoptosis.
      Integrating the compound-target network and stroke-related PPI network, we found
      that Akt1, HIF-1alpha and ITGB2 may play key roles in the treatment of stroke.
      The experiments demonstrated that oxycurcumenol may prevent PC12 cells from
      oxidative stress-induced cell damage. Our study indicates that XNJ has an effect
      on stroke by protecting neuro cells from oxidative stress-induced cell damage via
      HIF1alpha, and the research strategy at the systems pharmacology level is
      feasible to reveal the mechanisms of novel lead compounds from natural products.

PMID- 29336876
TI  - Structural Basis of Heterochromatin Formation by Human HP1.
AB  - Heterochromatin plays important roles in transcriptional silencing and genome
      maintenance by the formation of condensed chromatin structures, which determine
      the epigenetic status of eukaryotic cells. The trimethylation of histone H3
      lysine 9 (H3K9me3), a target of heterochromatin protein 1 (HP1), is a hallmark of
      heterochromatin formation. However, the mechanism by which HP1 folds chromatin
      containing H3K9me3 into a higher-order structure has not been elucidated. Here we
      report the three-dimensional structure of the H3K9me3-containing dinucleosomes
      complexed with human HP1alpha, HP1beta, and HP1gamma, determined by cryogenic
      electron microscopy with a Volta phase plate. In the structures, two H3K9me3
      nucleosomes are bridged by a symmetric HP1 dimer. Surprisingly, the linker DNA
      between the nucleosomes does not directly interact with HP1, thus allowing
      nucleosome remodeling by the ATP-utilizing chromatin assembly and remodeling
      factor (ACF). The structure depicts the fundamental architecture of
      heterochromatin.

PMID- 29336877
TI  - Sin-quadratic model for chest tomosynthesis respiratory signal analysis and its
      application in four dimensional chest tomosynthesis reconstruction.
AB  - Chest tomosynthesis (CTS) is a newly developed imaging technique which provides
      pseudo-3D volume anatomical information of thorax from limited-angle projections
      and contains much less of superimposed anatomy than the chest X-ray radiography.
      One of the relatively common problems in CTS is the patient respiratory motion
      during image acquisition, which negatively impacts the detectability. In this
      work, we propose a sin-quadratic model to analyze the respiratory motion during
      CTS scan, which is a real time method where the respiratory signal is generated
      by extracting the motion of diaphragm from projection radiographs. According to
      the estimated respiratory signal, the CTS projections were then amplitude-based
      sorted into four to eight phases, and an iterative reconstruction strategy with
      total variation regularization was adopted to reconstruct the CTS images at each
      phase. Simulated digital XCAT phantom data and three sets of patient data were
      adopted for the experiments to validate the performance of the sin-quadratic
      model and its application in four dimensional (4D) CTS reconstruction. Results of
      the XCAT phantom simulation study show that the correlation coefficient between
      the extracted respiratory signal and the originally designed respiratory signal
      is 0.9964, which suggests that the proposed model could exactly extract the
      respiratory signal from CTS projections. The 4D CTS reconstructions of both the
      phantom data and the patient data show clear reduction of motion-induced blur.

PMID- 29336878
TI  - Healing of Periapical Lesions after Endodontic Treatment with the GentleWave
      Procedure: A Prospective Multicenter Clinical Study.
AB  - INTRODUCTION: This report includes outcomes for a group of patients with
      significant periapical lesions who were treated and evaluated in two single-arm,
      multicenter, prospective, nonsignificant risk clinical studies. METHODS: Forty
      five teeth were from 45 patients who met the inclusion criteria and consented for
      the clinical studies and were diagnosed with periapical lesions with periapical
      index score >=3. Patients were treated with a standardized treatment protocol
      including instrumentation to an apical diameter of #20 without orifice
      enlargement, the GentleWave Procedure, and warm vertical obturation. Clinical
      signs and radiographic assessments were evaluated at 12 months to assess healing.
      Success was classified as healing or healed and accounted for the cumulative
      success rate of healing. Statistical analyses were performed by using Fisher
      exact test, Pearson correlation, and multivariate logistic regression analyses.
      RESULTS: At 12 months, 44 of 45 teeth (97.8%) were evaluated. The cumulative
      success rate for the GentleWave Procedure was 97.7%. Forty-three of 44 teeth were
      completely functional; all teeth had complete resolution for measured indices of
      mobility, soft tissue lesions, sinus tract, and furcation involvement. No
      patients experienced moderate or severe pain at 2, 7, and 14 days after
      procedure. Although only 1 patient was unsuccessful and the presence of clinical
      symptoms and type of periradicular diagnosis at 12 months were correlated with an
      unsuccessful outcome, the analyses were limited by the sample size. CONCLUSIONS:
      In this case series analysis, treatment of sizable periapical lesions with the
      GentleWave Procedure resulted in a success rate of 97.7% at 12-month re
      evaluation.

PMID- 29336879
TI  - Effect of Dynamic Immersion in Sodium Hypochlorite and EDTA Solutions on Cyclic
      Fatigue Resistance of WaveOne and WaveOne Gold Reciprocating Nickel-titanium
      Files.
AB  - INTRODUCTION: The purpose of this study was to evaluate the effect of sodium
      hypochlorite (NaOCl) and EDTA solutions on the cyclic fatigue resistance of
      WaveOne (WO) and WaveOne Gold (WOG) nickel-titanium reciprocating files. METHODS:
      A hundred WO (25/.08), and 100 WOG (25/.07) were randomly divided into 5 groups:
      group 1, no immersion; group 2, immersion in 5.25% NaOCl at 37 degrees C +/- 1
      degrees C for 5 minutes; group 3, immersion in 5.25% NaOCl at 37 degrees C +/- 1
      degrees C for 10 minutes; group 4, immersion in 17% EDTA at 37 degrees C +/- 1
      degrees C for 5 minutes; and group 5, immersion in 17 % EDTA at 37 degrees C +/-
      1 degrees C for 10 minutes. Then, the instruments were reciprocated in an
      artificial canal until fracture occurred, and the time to fracture was recorded.
      The data were statistically analyzed using 1-way analysis of variance and the
      Student t test via SPSS 21.0 software (IBM Corp, Armonk, NY) with the
      significance level set at P < .05. RESULTS: The cyclic fatigue resistance of the
      WOG was statistically higher than the WO in all the conditions tested (P < .05).
      There was no statistically significant difference among the different conditions
      tested in terms of cyclic fatigue resistance for both WO and WOG files (P > .05).
      Among the groups, there was no significant difference in the fracture lengths (P
      > .05). CONCLUSIONS: Within the limitations of the present study, it was
      determined that NaOCl and EDTA solutions did not have any effect on the cyclic
      fatigue resistance of WO and WOG files.

PMID- 29336880
TI  - Marginal Gaps between 2 Calcium Silicate and Glass Ionomer Cements and Apical
      Root Dentin.
AB  - INTRODUCTION: The outcome of periapical surgery has been directly improved with
      the introduction of novel material formulations. The aim of the study was to
      compare the retrograde obturation quality of the following materials: calcium
      silicate (Biodentine; Septodont, Saint-Maur-des-Fosses, France), mineral trioxide
      aggregate (MTA+; Cerkamed Company, Stalowa Wola, Poland), and glass ionomer
      cement (Fuji IX; GC Corporation, Tokyo, Japan). METHODS: Materials' wettability
      was calculated concerning the contact angles of the cements measured using a
      glycerol drop. Cements' porosity was determined using mercury intrusion
      porosimetry and micro-computed tomographic (MUCT) imaging. Extracted upper human
      incisors were retrofilled, and MUCT analysis was applied to calculate the volume
      of the gap between the retrograde filling material and root canal dentin.
      Experiments were performed before and after soaking the materials in simulated
      body fluid (SBF). RESULTS: No statistically significant differences were found
      among the contact angles of the studied materials after being soaked in SBF. The
      material with the lowest nanoporosity (Fuji IX: 2.99% and 4.17% before and after
      SBF, respectively) showed the highest values of microporosity (4.2% and 3.1%
      before and after SBF, respectively). Biodentine had the lowest value of
      microporosity (1.2% and 0.8% before and after SBF, respectively) and the lowest
      value of microgap to the root canal wall ([10 +/- 30] * 10-3 mm3). CONCLUSIONS:
      Biodentine and MTA possess certain advantages over Fuji IX for hermetic
      obturation of retrograde root canals. Biodentine shows a tendency toward the
      lowest marginal gap at the cement-to-dentin interface.

PMID- 29336881
TI  - Influence of Contracted Endodontic Access on Root Canal Geometry: An In Vitro
      Study.
AB  - INTRODUCTION: Contracted endodontic cavities (CECs) have developed from the
      concept of minimally invasive dentistry and provide an alternative to traditional
      endodontic cavities (TECs). They have been designed in an effort to preserve the
      mechanical stability of teeth. The contracted cavity design preserves more of the
      dentin but may influence the geometric shaping parameters. The aim of this micro
      computed tomographic study was to evaluate the influence of contracted endodontic
      cavities on the preservation of the original root canal anatomy after shaping
      with nickel-titanium rotary instruments. METHODS: Thirty extracted human
      mandibular molars with fully formed apices and independent mesial canals were
      randomly assigned to group 1 (TEC) and group 2 (CEC). Each group was shaped using
      ProGlider (Dentsply Maillefer, Ballaigues, Switzerland) and WaveOne Gold
      (Dentsply Maillefer). Irrigation was performed with 10% EDTA and 5% sodium
      hypochlorite. Samples were scanned before and after canal shaping to match canal
      volumes (SkyScan; Bruker microCT, Kontich, Belgium [100 kV, 100 MUA, and 15-MUm
      resolution]), and images were analyzed to evaluate canal volumes, surface areas,
      and centroid shift on cross sections at -1 mm and -3 mm from the apex. RESULTS:
      TECs showed a greater preservation of the original root canal anatomy with less
      apical transportation than CECs, possibly because of the absence of coronal
      interferences and, therefore, fewer pecking motions required to complete
      instrumentation. CONCLUSIONS: Within the limitations of this study, TECs may lead
      to a better preservation of the original canal anatomy during shaping compared
      with CECs, particularly at the apical level.

PMID- 29336882
TI  - Histobacteriologic Conditions of the Apical Root Canal System and Periapical
      Tissues in Teeth Associated with Sinus Tracts.
AB  - INTRODUCTION: This histobacteriologic study described the pattern of
      intraradicular and extraradicular infections in teeth with sinus tracts and
      chronic apical abscesses. METHODS: The material comprised biopsy specimens from
      24 (8 untreated and 16 treated) roots of teeth associated with apical
      periodontitis and a sinus tract. Specimens were obtained by periradicular surgery
      or extraction and were processed for histobacteriologic and histopathologic
      methods. RESULTS: Bacteria were found in the apical root canal system of all
      specimens, in the main root canal (22 teeth) and within ramifications (17 teeth).
      Four cases showed no extraradicular infection. Extraradicular bacteria occurred
      as a biofilm attached to the outer root surface in 17 teeth (5 untreated and 12
      treated teeth), as actinomycotic colonies in 2 lesions, and as planktonic cells
      in 2 lesions. Extraradicular calculus formation (mineralized biofilm) was evident
      in 10 teeth. CONCLUSIONS: Teeth with chronic apical abscesses and sinus tracts
      showed a very complex infectious pattern in the apical root canal system and
      periapical lesion, with a predominance of biofilms.

PMID- 29336883
TI  - Long-term Prognosis of Pulpal Status of Traumatized Teeth Exhibiting
      Contradictory Results between Pulp Sensibility Test and Ultrasound Doppler
      Flowmetry: A Retrospective Study.
AB  - INTRODUCTION: In this retrospective study, we investigated long-term (over 3
      years) follow-up results of teeth that exhibited contradictory results between
      the pulp sensibility test (thermal or electric pulp test) and ultrasound Doppler
      flowmetry (UDF) until 1 year after trauma to inspect the prognosis of the pulp.
      METHODS: Data were collected from the records of trauma patients in our hospital
      between February 2012 and May 2015. The teeth that had continuously shown
      contrasting results on the pulp sensibility test and UDF until 1 year after
      trauma were chosen for the study. Cases with follow-up records of more than 3
      years after trauma were finally included, and a retrospective chart review was
      performed. RESULTS: Data from 343 teeth in 147 patients who visited the hospital
      with traumatic dental injuries were examined. Among these, 13 teeth from 7
      patients were included, and the record of each case was reviewed. All the
      subjects showed negative responses on the pulp sensibility test and positive
      responses on UDF until 1 year after trauma. Ultimately, 8 of the 13 teeth
      recovered pulp sensibility. Two teeth failed to recover pulp sensibility and
      became symptomatic; root canal treatment was performed on the teeth. The
      remaining 3 teeth belonged to patients suffering from nerve damage; therefore,
      the pulp sensibility test was not feasible. CONCLUSIONS: Based on this study, UDF
      can be effectively used for the evaluation of pulpal status in traumatized teeth.

PMID- 29336884
TI  - Effect of Torsional and Fatigue Preloading on HyFlex EDM Files.
AB  - INTRODUCTION: The purpose of this study was to evaluate the effect of a low
      amount of torsional preloading on the fatigue life and different degrees of
      cyclic fatigue on torsional failure of HyFlex EDM (EDM; Coltene-Whaledent,
      Allstetten, Switzerland) and HyFlex CM (CM; Coltene-Whaledent) instruments.
      METHODS: EDM and CM files were used. The fatigue resistance was examined in a 5
      mm radius and 60 degrees  single curve, and the mean number of cycles to failure
      (Nf) was recorded. The torque and rotation angles at failure of the instruments
      were measured according to ISO 3630-1. New files were precycled to 0%, 50%, and
      75% of the Nf, and torsional tests were then performed. Other new files were
      preloaded at 5%, 15%, 25%, and 50% of the mean rotation angles before the fatigue
      test. The fracture surfaces of the fragments were examined under a scanning
      electron microscope. RESULTS: The fatigue resistance of EDM instruments was
      higher than that of CM instruments (P < .05). The torque and angle of rotation at
      fracture of the files were similar. Torsional preloading lowered the Nf of EDM at
      15% preloading (P < .05) and the Nf of CM at 50% preloading (P < .05). However,
      the Nf of EDM files even with 50% torsional preloading was significantly higher
      than unused CM files (P < .05). Fatigue prestressing even at 75% had no negative
      effect on the torque and rotation angle of the EDM files. Moderate precycling
      (50%) of EDM files increased their torsional resistance. The fractographic
      patterns corresponded to the pattern defined by the last stage test. CONCLUSIONS:
      A low amount (15%) of torsional preloading reduced the fatigue resistance of EDM
      files, whereas even extensive (75%) precyclic fatigue was not detrimental to
      their torsional resistance.

PMID- 29336885
TI  - Structural Basis for Activity and Specificity of an Anticoagulant Anti-FXIa
      Monoclonal Antibody and a Reversal Agent.
AB  - Coagulation factor XIa is a candidate target for anticoagulants that better
      separate antithrombotic efficacy from bleeding risk. We report a co-crystal
      structure of the FXIa protease domain with DEF, a human monoclonal antibody that
      blocks FXIa function and prevents thrombosis in animal models without detectable
      increased bleeding. The light chain of DEF occludes the FXIa S1 subsite and
      active site, while the heavy chain provides electrostatic interactions with the
      surface of FXIa. The structure accounts for the specificity of DEF for FXIa over
      its zymogen and related proteases, its active-site-dependent binding, and its
      ability to inhibit substrate cleavage. The inactive FXIa protease domain used to
      obtain the DEF-FXIa crystal structure reversed anticoagulant activity of DEF in
      plasma and in vivo and the activity of a small-molecule FXIa active-site
      inhibitor in vitro. DEF and this reversal agent for FXIa active-site inhibitors
      may help support clinical development of FXIa-targeting anticoagulants.

PMID- 29336886
TI  - Can the Syndesmosis Procedure Prevent Metatarsus Primus Varus and Hallux Valgus
      Deformity Recurrence? A 5-Year Prospective Study.
AB  - One of the main objectives of hallux valgus surgery is correction of the
      metatarsus primus varus deformity by osteotomy, arthrodesis, or soft tissue
      correction. The syndesmosis procedure uses intermetatarsal cerclage sutures to
      realign the first metatarsal and also induces a syndesmotic bonding between the
      first and second metatarsals to prevent metatarsus primus varus deformity
      recurrence. The purpose of the present study was to demonstrate radiologic
      evidence of the effectiveness of the syndesmosis concept and to identify the
      incidence and nature of deformity recurrence. A total of 55 feet from 60
      consecutive procedures were followed regularly at 6 fixed points for 5 years. The
      radiologic inclusion criterion was a first intermetatarsal angle >9 degrees  or
      metatarsophalangeal angle >20 degrees . The initial postoperative radiographs
      showed significant correction of the intermetatarsal angle from a preoperative
      average of 14.5 degrees  to 4.3 degrees  (p < .0001). It had increased to 7.0
      degrees  during the first 6 postoperative months but remained within the normal
      upper limit of 9 degrees  and exhibited no further significant changes for the
      subsequent 4.5 years (p = .0792). Hallux valgus deformity correction also
      correlated with metatarsus primus varus deformity correction. Three (5%) second
      metatarsal stress fractures occurred, and all recovered uneventfully. In
      conclusion, we have report the findings from a detailed medium long-term follow
      up study showing, to the best of our knowledge, for the first time that
      metatarsus primus varus and hallux valgus deformities can be effectively
      corrected and maintained using a specific surgical technique. Also included are 6
      relevant radiographs and photographs of the included and excluded feet in the
      online Supplementary Material for reference.

PMID- 29336887
TI  - GroEL Ring Separation and Exchange in the Chaperonin Reaction.
AB  - The bacterial chaperonin GroEL and its cofactor, GroES, form a nano-cage for a
      single molecule of substrate protein (SP) to fold in isolation. GroEL and GroES
      undergo an ATP-regulated interaction cycle to close and open the folding cage.
      GroEL consists of two heptameric rings stacked back to back. Here, we show that
      GroEL undergoes transient ring separation, resulting in ring exchange between
      complexes. Ring separation occurs upon ATP-binding to the trans ring of the
      asymmetric GroEL:7ADP:GroES complex in the presence or absence of SP and is a
      consequence of inter-ring negative allostery. We find that a GroEL mutant unable
      to perform ring separation is folding active but populates symmetric GroEL:GroES2
      complexes, where both GroEL rings function simultaneously rather than
      sequentially. As a consequence, SP binding and release from the folding chamber
      is inefficient, and E. coli growth is impaired. We suggest that transient ring
      separation is an integral part of the chaperonin mechanism.

PMID- 29336890
TI  - Some notes on citrulline in the CNS.

PMID- 29336889
TI  - KRAS Dimerization Impacts MEK Inhibitor Sensitivity and Oncogenic Activity of
      Mutant KRAS.
AB  - The mechanism by which the wild-type KRAS allele imparts a growth inhibitory
      effect to oncogenic KRAS in various cancers, including lung adenocarcinoma
      (LUAD), is poorly understood. Here, using a genetically inducible model of KRAS
      loss of heterozygosity (LOH), we show that KRAS dimerization mediates wild-type
      KRAS-dependent fitness of human and murine KRAS mutant LUAD tumor cells and
      underlies resistance to MEK inhibition. These effects are abrogated when wild
      type KRAS is replaced by KRASD154Q, a mutant that disrupts dimerization at the
      alpha4-alpha5 KRAS dimer interface without changing other fundamental biochemical
      properties of KRAS, both in vitro and in vivo. Moreover, dimerization has a
      critical role in the oncogenic activity of mutant KRAS. Our studies provide
      mechanistic and biological insights into the role of KRAS dimerization and
      highlight a role for disruption of dimerization as a therapeutic strategy for
      KRAS mutant cancers.

PMID- 29336888
TI  - LXR/ApoE Activation Restricts Innate Immune Suppression in Cancer.
AB  - Therapeutic harnessing of adaptive immunity via checkpoint inhibition has
      transformed the treatment of many cancers. Despite unprecedented long-term
      responses, most patients do not respond to these therapies. Immunotherapy non
      responders often harbor high levels of circulating myeloid-derived suppressor
      cells (MDSCs)-an immunosuppressive innate cell population. Through genetic and
      pharmacological approaches, we uncovered a pathway governing MDSC abundance in
      multiple cancer types. Therapeutic liver-X nuclear receptor (LXR) agonism reduced
      MDSC abundance in murine models and in patients treated in a first-in-human dose
      escalation phase 1 trial. MDSC depletion was associated with activation of
      cytotoxic T lymphocyte (CTL) responses in mice and patients. The LXR
      transcriptional target ApoE mediated these effects in mice, where LXR/ApoE
      activation therapy elicited robust anti-tumor responses and also enhanced T cell
      activation during various immune-based therapies. We implicate the LXR/ApoE axis
      in the regulation of innate immune suppression and as a target for enhancing the
      efficacy of cancer immunotherapy in patients.

PMID- 29336891
TI  - Cupuacu extract reduces nitrosative stress and modulates inflammatory mediators
      in the kidneys of experimental diabetes.
AB  - BACKGROUND & AIMS: We have previously reported an increased nitrosative stress in
      the kidneys of diabetic animals, which was reduced by an antioxidant probiotic.
      The present study evaluated whether the extract of cupuacu (EC), an antioxidant
      compound rich in polyphenols and theograndins, when administered at a dose that
      can be reasonably obtained through daily consumption, could delay the onset of
      diabetic complications in the kidney. METHODS: Mouse immortalized mesangial cells
      (MiMC) were placed in medium normal glucose (NG) or high glucose (HG), with or
      without EC (500, 100, 50 or 10 MUg/mL) during 24, 48 or 72 h for analysis of
      viability, proliferation, nitric oxide (NO) levels and reactive oxygen species or
      nitrogen (ROS/RNS). Male, adult Wistar rats were distributed in 4 groups: control
      (CTL) and diabetic (DM) who received water; CTLEC and DMEC who received 1 mL/day
      of EC (1 g/mL), via gavage for 8 consecutive weeks. After, metabolic profile and
      renal function were evaluated and, kidneys were collected for analysis of NO,
      ROS, 3-nitrotyrosine (3-NT), endothelial nitric oxide synthase (eNOS), IL-6, IL
      10, TNF-alpha and NF-kappaB p65. RESULTS: The MiMC showed normal viability in all
      groups, demonstrating that EC had no cytotoxic effect at doses on 24, 48 or 72 h.
      MiMC under HG presented significant increase in proliferation, NO and ROS vs. NG;
      these parameters were significantly reduced after 72 h of EC treatment (P <
      0.05). DMEC showed a significant reduction of feed intake, ROS and NO, 3-NT, IL-6
      and eNOS vs. DM (P < 0.05). Supplementation with EC at a dose consumed daily
      could improve control of nitrosative stress, combined with reduction of
      inflammatory factors, suggesting the importance of bioactive compounds as non
      pharmacological adjuvant therapy to delay kidney complications in diabetic
      patients.

PMID- 29336892
TI  - Gene therapy and gene editing strategies for hemoglobinopathies.
AB  - Gene therapy for hemoglobinopathies is currently based on transplantation of
      autologous hematopoietic stem cells genetically modified with an integrating
      lentiviral vector expressing a globin gene under the control of globin
      transcriptional regulatory elements. Studies and safety works demonstrated the
      potential therapeutic efficacy and safety of this approach, providing the
      rationale for clinical translation. The outcomes of early clinical trials,
      although showing promising results, have highlighted the current limitations to a
      more general application. These include the nature, source and age of
      repopulating hematopoietic stem cells, the suboptimal transduction efficiency and
      gene expression levels, the toxicity and efficacy of bone marrow conditioning,
      the stress status of bone marrow microenvironment in chronic diseases such as
      beta-thalassemia and sickle cell disease. Recently, gene editing strategies based
      on the use of nucleases offered a novel approach to increase globin expression in
      a quasi-physiological way, independently from the addition of transgenes and
      viral sequences to the human genome. This review will discuss the current status
      of gene therapy for beta-thalassemia and sickle cell disease with a perspective
      towards the improvements necessary in the context of clinical translation.

PMID- 29336893
TI  - A meta-analysis of the utility of the neutrophil-to-lymphocyte ratio in
      predicting survival after pancreatic cancer resection.
AB  - BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) is thought to reflect cancer
      disease burden. To assess the prognostic ability of the NLR on overall survival
      in patients with resectable, pancreatic cancer a meta-analysis of published
      literature was undertaken. METHOD: A systematic review was performed
      independently by two authors using PubMed, Ovid MEDLINE and Embase databases.
      Included studies detailed the pre-operative NLR and overall survival of
      pancreatic cancer patients. RESULTS: Of the 214 studies retrieved using the
      search strategy, 8 studies involving 1519 patients were included in the meta
      analysis. Only one study did not find a statistically significant association
      between a high NLR and OS. The pooled Hazard Ratio was 1.77 (95% CI [1.45-2.15];
      p < 0.01). The NLR cut-off values ranged from 2 to 5. There was low to moderate
      inter-study heterogeneity (I2 = 31%; p = 0.17), a low risk of intra-study bias,
      and potentially 3 unpublished (negative) studies. CONCLUSIONS: A high pre
      operative NLR indicates a worse prognosis than in patients with a low NLR. There
      is potential to use the NLR to direct therapies. A specific cut-off value has not
      been established from this study and so further research is required.

PMID- 29336894
TI  - Preoperative surveillance rectal swab is associated with an increased risk of
      infectious complications in pancreaticoduodenectomy and directs antimicrobial
      prophylaxis: an antibiotic stewardship strategy?
AB  - BACKGROUND: Despite improvements in the perioperative care, the morbidity rate
      after pancreaticoduodenectomy (PD) is still higher than 50%. The aim of this
      study was twofold: first, to assess the correlation between preoperative rectal
      swab (RS) and intraoperative bile cultures; to examine the impact of RS isolates
      on postoperative course after PD. METHODS: An observational study was conducted
      analyzing all consecutive PD performed from January 2015 to July 2016. Based on
      the positivity/negativity of preoperative RS for multi-drug resistant bacteria,
      two groups of patients were identified (RS+ vs. RS-) and then compared. RESULTS:
      Three hundred thirty-eight patients were considered for the analysis. RS culture
      showed a perfect correlation (species and phenotypic antibiotic susceptibility
      pattern) with bile culture in 157 patients (86.7%). Fifty patients (14.8%) had a
      RS+. Preoperative biliary drain (PBD) was the single independent preoperative
      risk factor associated to RS+ (p = 0.021, OR = 2.6, 95% CI = 1.5-11.7). Infective
      complications (IC) and mortality were independently correlated to RS+ (p = 0.013,
      OR = 2.9, 95% CI = 1.3-6.7; p = 0.009 OR = 3.4, 95% CI = 1.8-14.9, respectively).
      CONCLUSIONS: Preoperative surveillance RS-culture's positivity correlates to
      biliary colonization that occurs after PBD. IC and mortality after PD are
      associated with RS+. Preoperative RS can direct antibiotic prophylaxis to reduce
      morbidity and mortality after PD.

PMID- 29336895
TI  - Alterations in peripheral fatty acid composition in bipolar and unipolar
      depression.
AB  - BACKGROUND: Lipid metabolism has been shown to play an important role in unipolar
      and bipolar depression. In this study, we aimed to evaluate levels of fatty acids
      in patients with unipolar (MDD) and bipolar depression (BDD) in comparison to
      patients with bipolar disorder in euthymia (BDE) and non-psychiatric controls.
      METHODS: Levels of saturated fatty acids (SFAs), monounsaturated fatty acids
      (MUFAs) and polyunsaturated fatty acids (PUFAs) were assessed in serum of (87)
      patients with BD (31 euthymic, 22 depressive) or MDD (34) and (31) non
      psychiatric controls through GC-FID. RESULTS: No significant difference in total
      levels of PUFAs (polyunsaturated fatty acids), SFAs (saturated fatty acids),
      MUFAs (monounsaturated fatty acids) and total fatty acids were found between
      groups. Our results demonstrated higher levels AA: EPA and AA: EPA+DHA in
      patients with BDD. Additionally, we observed that overall omega-6 present a
      positive correlation with illness duration in patients with BDD and AA: EPA ratio
      positively associated with illness duration in MDD group. Depression severity was
      positively associated with AA: EPA+DHA ratio in all participants. CONCLUSION:
      Together, our results support the relevance for the balance of omega-3 and omega
      6 in BDD. Also, our results suggest a potential subset of stage-related lipid
      biomarkers that further studies are needed to help clarify the dynamics of lipid
      alteration in BD and MDD.

PMID- 29336896
TI  - Targeted Retinal Photocoagulation for Diabetic Macular Edema with Peripheral
      Retinal Nonperfusion: Three-Year Randomized DAVE Trial.
AB  - PURPOSE: To evaluate the effect of targeted retinal photocoagulation (TRP) on
      visual and anatomic outcomes and treatment burden in eyes with diabetic macular
      edema (DME). DESIGN: Phase I/II prospective, randomized, controlled clinical
      trial. PARTICIPANTS: Forty eyes of 29 patients with center-involved macular edema
      secondary to diabetes mellitus. METHODS: Eyes with center-involved DME and Early
      Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA)
      between 20/32 and 20/320 (Snellen equivalent) were randomized 1:1 to monotherapy
      with 0.3 mg ranibizumab (Lucentis, Genentech, South San Francisco, CA) or
      combination therapy with 0.3 mg ranibizumab and TRP guided by widefield
      fluorescein angiography. All eyes received 4 monthly ranibizumab injections
      followed by monthly examinations and pro re nata (PRN) re-treatment through 36
      months. Targeted retinal photocoagulation was administered outside the macula to
      areas of retinal capillary nonperfusion plus a 1-disc area margin in the
      combination therapy arm at week 1, with re-treatment at months 6, 18, and 25, if
      indicated. MAIN OUTCOME MEASURES: Mean change in ETDRS BCVA from baseline and
      number of intravitreal injections administered. RESULTS: At baseline, mean age
      was 55 years, mean BCVA was 20/63 (Snellen equivalent), and mean central retinal
      subfield thickness (CRT) was 530 MUm. Thirty-four eyes (85%) completed month 36,
      at which point mean BCVA improved 13.9 and 8.2 letters (P = 0.20) and mean CRT
      improved 302 and 152 MUm (P = 0.03) in the monotherapy and combination therapy
      arms, respectively. The mean number of injections administered through month 36
      was 24.4 (range, 10-34) and 27.1 (range, 12-36), with 73% (362/496) and 80%
      (433/538) of PRN injections administered (P = 0.004) in the monotherapy and
      combination therapy arms, respectively. Goldmann visual field isopter III-4e area
      decreased by 2% and 18% in the monotherapy and combination therapy arms,
      respectively (P = 0.30). CONCLUSIONS: In this 3-year randomized trial of 40 eyes
      with DME, there was no evidence that combination therapy with ranibizumab and TRP
      improved visual outcomes or reduced treatment burden compared with ranibizumab
      alone.

PMID- 29336897
TI  - The Real-World Effect of Intravitreous Anti-Vascular Endothelial Growth Factor
      Drugs on Intraocular Pressure: An Analysis Using the IRIS Registry.
AB  - PURPOSE: To identify sustained differences in intraocular pressure (IOP) after
      intravitreous injections of anti-vascular endothelial growth factor (VEGF) drugs.
      DESIGN: Database study. PARTICIPANTS: Patients seeing an ophthalmic provider who
      contributes to the database. METHODS: We identified a total of 23 776 unique
      patients who received only a single type of anti-VEGF medication (bevacizumab,
      aflibercept, or ranibizumab) by injection in the right eye in the American
      Academy of Ophthalmology Intelligent Research in Sight Registry. Subgroups
      included patients with age-related macular degeneration only and patients who had
      not received an anti-VEGF injection for at least 1 year before the study. We
      examined those with at least 12, 18, and 25 injections for each of these 3
      medications. For all groups, we used fellow, untreated eyes for comparison. MAIN
      OUTCOME MEASURES: The mean change in IOP from baseline at a minimum of 1 year of
      follow-up and the proportion of eyes with a clinically significant IOP increase
      (defined as sustained rise of at least 6 mmHg to an IOP of more than 21 mmHg).
      RESULTS: All patients in all groups receiving all drugs showed a decrease in IOP
      from baseline, with a mean of 0.9 mmHg in treated eyes compared with an average
      decrease of 0.2 mmHg in fellow untreated eyes, a statistically significant
      difference. A generalized linear model accounting for confounders associated
      bevacizumab with slightly less lowering of IOP than aflibercept and ranibizumab
      in most subgroups. A clinically significant IOP increase was seen in 2.6% of eyes
      receiving injections compared with 1.5% in the associated untreated fellow eyes.
      Clinically significant IOP increases occurred at a rate of 1.9%, 2.8%, and 2.8%
      for aflibercept, ranibizumab, and bevacizumab, respectively, which was
      significantly higher than untreated fellow eyes for bevacizumab and ranibizumab,
      but not for aflibercept. CONCLUSIONS: These analyses from real-world data
      indicate that anti-VEGF intravitreous injections are associated with a small but
      statistically significant decrease in IOP over time. A proportion of patients, on
      average 2.6%, experienced a sustained clinically significant IOP rise with these
      drugs overall compared with 1.5% in the fellow untreated eyes. However, such an
      increase was not seen with aflibercept.

PMID- 29336898
TI  - Effect of transcranial direct current stimulation on short-term and long-term
      treatment of chronic tinnitus.
AB  - OBJECTIVE: This study was conducted to investigate the effectiveness of anodal
      and cathodal methods in reducing the intensity of tinnitus and to compare them
      with the control. METHODOLOGY: This randomized double-blind clinical trial with
      case and control groups was conducted in Al-Zahra Hospital in Isfahan between
      2015 and 2016. In this trial, 51 patients with tinnitus, for at least one year,
      were selected among those outpatients visiting the throat, nose and ear clinic
      within this period. Inclusion criteria were patients on electrical stimulation
      prohibition, with Meniere's disease, otosclerosis, chronic headache, and
      pulsatile tinnitus. Patients were randomly divided in three equal-sized groups:
      anodal stimulation group, cathodal stimulation group, and control group. The
      subjects received 20-min current stimulation (2 mA). Five subjects were selected
      from those with a significant difference between the stimulated states (anodal or
      cathodal) and/or control. They received weekly transcranial electrical
      stimulation for two months, and their long-term recovery from tinnitus was
      investigated. Data analysis was done with SPSS20. RESULTS: Findings showed no
      significant between-groups difference in mean scores of tinnitus before the
      intervention (p = .68); whereas, this difference was significant immediately
      after the intervention (p = .02) and 1 h after it (p = .03). The mean score of
      tinnitus in the anodal stimulation group was significantly lower than the
      control; whereas, no significant difference was observed between the anodal and
      cathodal stimulation groups, and between the cathodal and control groups (p <
      .05). Findings also showed that the mean scores of tinnitus in two cathodal
      stimulation groups (p = .24) and control group (p = .62) were not significantly
      different at three different points of time; whereas, this score was
      significantly different in the anodal group at these time points (p = .01).
      CONCLUSION: In conclusion, anodal stimulation was more effective than the
      cathodal and control stimulation in reducing the intensity of tinnitus in the
      short term.

PMID- 29336899
TI  - Commentary on letter to the editor on manuscript "Image analysis of
      interarytenoid area to detect cases of Laryngopharyngeal Reflux: An objective
      method".

PMID- 29336900
TI  - Combined use of a nanocarbon suspension and 99mTc-MIBI for the intra-operative
      localization of the parathyroid glands.
AB  - OBJECTIVE: To investigate the combined use of a nanocarbon (NC) suspension and
      low-dose 99mTc-MIBI for parathyroid localization during surgery in patients with
      secondary hyperparathyroidism (sHPT). METHODS: Between March 2010 and September
      2015, 40 patients with sHPT were enrolled in this study and were randomized to
      receive either low-dose 99mTc-MIBI+NC (group I) or low-dose 99mTc-MIBI (group
      II). Pre- and post-operative serum levels of intact PTH (iPTH), calcium and
      phosphorus between groups were compared and the intra-operative radioactive
      counts of the parathyroid glands were measured. RESULTS: The post-operative iPTH
      level was significantly lower in patients of group I (24.2+/-31ng/L) than in
      those of group II (106+/-155ng/L) (P=0.03) while there were no significant
      differences in intra-operative parathyroid gland radioactive counts between the
      groups. The duration of the surgical procedure was shorter for patients of group
      I than patients of group II. There were no serious intra-operative or post
      operative complications. CONCLUSION: The combined use of an NC suspension and
      99mTc-MIBI for patients with sHPT is strongly recommended for the localization of
      parathyroid glands during surgery and is likely to improve clinical outcomes for
      patients.

PMID- 29336901
TI  - Image analysis of the interarytenoid area to detect laryngopharyngeal reflux
      disease.

PMID- 29336902
TI  - Surgical management of pulsatile tinnitus secondary to jugular bulb or sigmoid
      sinus diverticulum with review of literature.
AB  - INTRODUCTION: Jugular bulb and sigmoid sinus anomalies are well-known causes of
      vascular pulsatile tinnitus. Common anomalies reported in the literature include
      high-riding and/or dehiscent jugular bulb, and sigmoid sinus dehiscence. However,
      cases of pulsatile tinnitus due to diverticulosis of the jugular bulb or sigmoid
      sinus are less commonly encountered, with the best management option yet to be
      established. In particular, reports on surgical management of pulsatile tinnitus
      caused by jugular bulb diverticulum have been lacking in the literature.
      OBJECTIVES: To report two cases of pulsatile tinnitus with jugular bulb and/or
      sigmoid sinus diverticulum, and their management strategies and outcomes. In this
      series, we describe the first reported successful case of pulsatile tinnitus due
      to jugular bulb diverticulum that was surgically-treated. SUBJECTS AND METHODS:
      Two patients diagnosed with either jugular bulb and/or sigmoid sinus
      diverticulum, who had presented to the Otolaryngology clinic with pulsatile
      tinnitus between 2016 and 2017, were studied. Demographic and clinical data were
      obtained, including their management details and clinical outcomes. RESULTS: Two
      cases (one with jugular bulb diverticulum and one with both sigmoid sinus and
      jugular bulb diverticula) underwent surgical intervention, and both had immediate
      resolution of pulsatile tinnitus post-operatively. This was sustained at
      subsequent follow-up visits at the outpatient clinic, and there were no major
      complications encountered for both cases intra- and post-operatively. CONCLUSION:
      Transmastoid reconstruction/resurfacing of jugular bulb and sigmoid sinus
      diverticulum with/without obliteration of the diverticulum is a safe and
      effective approach in the management of bothersome pulsatile tinnitus arising
      from these causes.

PMID- 29336903
TI  - One-year experience of a regional service model of teleconsultation for planning
      and treatment of complex thoracoabdominal aortic disease.
AB  - OBJECTIVE: The objective of this study was to report the methodology and 1-year
      experience of a regional service model of teleconsultation for planning and
      treatment of complex thoracoabdominal aortic disease (TAAD). METHODS: Complex
      TAADs without a feasible conventional surgical repair were prospectively
      evaluated by vascular surgeons of the same public health service (National Health
      System) located in a huge area of 22,994 km2 with 3.7 million inhabitants and 11
      tertiary hospitals. Surgeons evaluated computed tomography scans and clinical
      details that were placed on a web platform (Google Drive; Google, Mountain View,
      Calif) and shared by all surgeons. Patients gave informed consent for the
      teleconsultation. The surgeon who submits a case discusses in detail his or her
      case and proposes a possible therapeutic strategy. The other surgeons suggest
      other solutions and options in terms of grafts, techniques, or access to be used.
      Computed tomography angiography, angiography, and clinical outcomes of cases are
      then presented at the following telemeetings, and a final agreement of the
      operative strategy is evaluated. Teleconsultation is performed using a web
      conference service (WebConference.com; Avaya Inc, Basking Ridge, NJ) every month.
      An inter-rater agreement statistic was calculated, and the kappa value was
      interpreted according to Altman's criteria for computed tomography angiography
      measurements. RESULTS: The rate of participation was constant (mean number of
      surgeons, 11; range, 9-15). Twenty-four complex TAAD cases were discussed for
      planning and operation during the study period. The interobserver reliability
      recorded was moderate (kappa = 0.41-0.60) to good (kappa = 0.61-0.80) for
      measurements of proximal and distal sealing and very good (kappa = 0.81-1) for
      detection of any target vessel angulation >60 degrees, significant calcification
      (circumferential), and thrombus presence (>50%). The concordance for planning and
      therapeutic strategy among all participants was complete in 16 cases. In one
      case, the consultation was decisive for creating an innovative therapeutic
      strategy; in the remaining seven cases, the strategy proposed by the patient's
      surgeon was changed completely after the discussion. Technical success was the
      same (100%) if concordance in planning was present initially or not. Overall 6
      month mortality was 4%, 0% for those patients with initial concordance in
      planning vs 12% for those without initial concordance (P = .33). Surgery was
      always performed in a tertiary hospital by local surgeons, and in two cases (8%)
      external surgeons joined the local surgical team. CONCLUSIONS: Such a regional
      service of teleconsultation may be of value in standardizing the treatment and
      derived costs of complex TAADs in a huge region under the same health provider.
      The shared decision-making strategy may be of medical-legal value as well.

PMID- 29336905
TI  - Getting a good night sleep? The importance of recognizing and treating nocturnal
      hypokinesia in Parkinson's disease.
AB  - When Parkinson's disease (PD) patients are asked about the quality of their
      sleep, their answers are dominated by difficulties associated with impaired
      mobility in bed, medically referred to as nocturnal hypokinesia. Nocturnal
      hypokinesia is symptomatic from the mid-stage of the disease, affecting up to 70%
      of PD patients, and contributes to poor sleep quality, and increased carer
      burden. Here we explore four areas of nocturnal hypokinesia that are relevant to
      clinical practice, namely: manifestations and definition; clinical assessment and
      objective monitoring; etiologies and contributing factors; and evidence-based
      therapeutic approaches. In addition, we provide an operational definition of what
      constitutes nocturnal hypokinesia and outline different methods of assessment,
      ranging from clinical interviews and rating scales to objective night-time
      monitoring with inertial sensors. Optimal management of nocturnal hypokinesia in
      PD begins with recognizing its manifestation by inquiring about cardinal symptoms
      and contributing factors from, not only patients, but also carers, followed by
      formal assessment, and the application of individualized evidence-based
      treatment. Night-time dopaminergic treatment is the primary therapy; however,
      careful clinical judgment is required to balance the benefits with the potential
      adverse events related to nocturnal dopaminergic stimulation. Future studies are
      needed to explore the practicality of home-based objective assessment of
      nocturnal hypokinesia, new therapeutic options not limited to dopaminergic
      medications, and non-pharmacologic approaches, including training on compensatory
      strategies and bedroom adaptations.

PMID- 29336904
TI  - Bypass versus endovascular intervention for healing ischemic foot wounds
      secondary to tibial arterial disease.
AB  - OBJECTIVE: Pedal (inframalleolar) bypass is a long-standing therapy for tibial
      arterial disease in patients with ischemic tissue loss. Endovascular tibial
      intervention is an appealing alternative with lower risks of perioperative
      mortality or complications. Our objective was to compare the effectiveness of
      these two treatment modalities with respect to patency and limb-related clinical
      outcomes. METHODS: We performed a retrospective chart review of patients
      presenting between 2006 and 2013 with ischemic foot wounds and infrapopliteal
      arterial disease who underwent a revascularization procedure (either open
      surgical bypass to an inframalleolar target or endovascular tibial intervention).
      Data were collected on baseline demographics and comorbidities, procedural
      details, and postprocedure outcomes. The primary outcome was successful healing
      of the index wound, with mortality, major amputation, and patency assessed as
      secondary outcomes. RESULTS: We identified 417 patients who met our eligibility
      criteria; 105 underwent surgical bypass and 312 underwent endovascular
      intervention, with mean follow-up of 25.0 and 20.2 months, respectively (P =
      .08). The endovascular patients were older at baseline (P = .009), with higher
      rates of hyperlipidemia (P = .02), prior cerebrovascular accidents (P = .04), and
      smoking history (P = .04). Within 30 days postoperatively, there was no
      difference in mortality (P = .31), but bypass patients had longer hospital length
      of stay (P < .0001), higher rate of discharge to nursing facility (P < .001), and
      higher rates of myocardial infarctions (P = .03) and wound complications (P <
      .001). At 6 months, the rate of wound healing was 22.4% in the bypass group
      compared with 29.0% in the endovascular group (P = .02). At 1 year, survival was
      higher after bypass (86.2% vs 70.4%; P < .0001), but freedom from major
      amputation was similar (84.9% vs 82.8%; P = .42). Primary patency (53.1% vs
      38.2%; P = .002) and primary assisted patency (76.6% vs 51.7%; P < .0001) were
      higher in the bypass group, but there was no difference in secondary patency
      (77.3% vs 73.8%; P = .13). CONCLUSIONS: Endovascular tibial intervention is
      associated with poorer primary patency but similar secondary patency and wound
      healing rates compared with the "gold standard" of surgical bypass to a pedal
      target. In patients with tibial arterial disease, endovascular intervention
      should be considered a lower risk alternative to pedal bypass that provides
      similar clinical outcomes.

PMID- 29336906
TI  - Progression of white matter damage in progressive supranuclear palsy with
      predominant parkinsonism.
AB  - INTRODUCTION: Progressive supranuclear palsy with predominant parkinsonism (PSP
      P) accounts for 14-35% of all PSP cases. A few cross-sectional MRI studies in PSP
      P showed a remarkable white matter (WM) damage. Progression of brain structural
      damage in these patients remains unknown. METHODS: Longitudinal clinical,
      cognitive and diffusion tensor (DT) MRI data were obtained over a mean 1.6 year
      follow up in 10 PSP-P patients. At study entry, patients were compared with 36
      healthy controls. Voxelwise statistical analysis of white matter DT MRI data
      (mean, axial and radial diffusivity, and fractional anisotropy) was carried out
      using tract-based spatial statistics. RESULTS: During the 1.6 year follow up, PSP
      P patients showed significant decline of motor, cognitive and mood disturbances.
      DT MRI analysis revealed at baseline a widespread pattern of WM alterations. Over
      time, PSP-P patients exhibited progression of WM damage in supratentorial tracts
      compared to baseline. No WM changes were detected in cerebellar WM. CONCLUSIONS:
      In PSP-P patients, WM damage significantly progressed over time. Longitudinal DT
      MRI measures are a potential in vivo marker of disease progression in PSP-P.

PMID- 29336907
TI  - A Palliative Approach to Falls in Advanced Dementia.
AB  - Falls are viewed as a preventable cause of injury, functional loss, and death in
      older adults with dementia, and have been used as a marker of quality of care in
      long-term care facilities. Despite intensive intervention around fall prevention
      in these settings, falls and injury remain frequent, particularly among residents
      in the advanced stages of dementia. In this clinical review, we consider the
      common challenges and pitfalls in both the management of falls and the provision
      of palliative care in advanced dementia. We then describe a palliative approach
      to falls in advanced dementia that involves identifying individuals who would
      benefit from this care approach, framing falls and loss of mobility as a quality
      of life issue, and devising an individualized symptom assessment and management
      plan. A palliative approach can lead to recognition and acceptance that recurrent
      falls are often symptomatic of advanced dementia, and that not all falls are
      preventable. We conclude that falls in the advanced stage of dementia can be
      sentinel events indicating the need for a palliative approach to care. Rather
      than replace falls prevention activities, a palliative approach to falls prompts
      us to select dementia stage-appropriate interventions with a focus on symptom
      management, comfort, and dignity.

PMID- 29336908
TI  - Re: Sentinel node biopsy in desmoplastic thin melanoma: Histogenetic
      recommendations.

PMID- 29336909
TI  - [Non reported spa types in our country in Staphylococcus aureus from adult
      patients of a school hospital, Santa Fe - Argentina].
AB  - Staphylococcus aureus is a pathogen associated a different kind of infection.
      Molecular markers are useful tools to study microbial epidemiology. Twenty two
      methicillin-resistant S. aureus (MRSA) and 23 methicillin-susceptible S. aureus
      (MSSA) were studied by mecA gene, SCCmec cassette, Panton Valentine leucocidin
      (PVL) and spa polymorphism. The clinical data patients were analyzed. MSSA was
      prevalent in samples different from skin and soft tissue (SST) and in
      hospitalized patients, whereas MRSA in SST. SCCmec type IV was predominant,
      followed by type I. Low presence of PVL was found. In MRSA 11 different types of
      spa were detected, t019 was the most frequent and associated with outpatient, 17
      types were found in MSSA and t189 was prevalent. spa t002 was present in MSSA and
      MRSA. We found 11 types of spa not reported in our country.

PMID- 29336910
TI  - Bioconversion of hemicellulosic materials into ethanol by yeast, Pichia
      kudriavzevii 2-KLP1, isolated from industrial waste.
AB  - In the present work, a yeast strain Pichia kudriavzevii was identified on the
      basis of 18S rDNA, showing maximum growth at 30 degrees C and pH 7.0. Among all
      the complex polysaccharides used, wheat bran proved to be the best substrate as
      indicated by the maximum growth of the yeast strain. The yeast isolate was
      capable of producing xylanase both intra- and extra-cellularly, the dominant form
      being extracellular. The maximum enzyme activity was determined at pH 5.0 and at
      50 degrees C. Na+, Mg2+ and Fe2+ presence caused a substantial increase in enzyme
      activity while a slight decrease (4.5%) was observed in the presence of Mn2+,
      Zn2+ and Cu2+. Pyruvate decarboxylase (PDC) and alcohol dehydrogenase (ADH)
      activities were assayed to confirm the presence of the ethanol pathway and PDC
      activity was much more pronounced (73%) compared to ADH activity (51%). The yeast
      strain can be employed to utilize hemicellulose containing agroindustrial
      residues for ethanol production.

PMID- 29336911
TI  - [Detection and characterization of Shiga toxin-producing Escherichia coli in
      children treated at an inter-zonal pediatric hospital in the city of La Plata].
AB  - Shiga toxin-producing Escherichia coli (STEC) is a foodborne pathogen that can
      cause watery diarrhea, bloody diarrhea (BD), and hemolytic uremic syndrome (HUS).
      The objective of this study was to determine the phenotypic and genotypic
      profiles of STEC strains isolated from children with BD and HUS treated at a
      pediatric hospital in the city of La Plata in the period 2006-2012, and to
      establish the clonal relationship of O157:H7 isolates by pulsed field
      electrophoresis. The percentage of positive samples was 4.9% and 39.2% in
      patients with BD and HUS, respectively. Seventy-seven STEC strains from 10
      different serotypes were isolated, with 100% colony recovery, O157:H7 being the
      most frequent (71.4%) serotype, followed by O145:NM (15.6%). An average of 98.2%
      of O157:H7 isolates belonged to biotype C and were sensitive to all the
      antibiotics tested. All of them (100%) carried genotype stx2, eae, fliCH7, ehxA,
      iha, efa, toxB, lpfA1-3 and lpfA2-2. When the clonal relationship of the O157:H7
      strains was studied, a total of 42 patterns with at least 88% similarity were
      identified, and 6 clusters with identical profiles were established. The eae
      negative isolates belonged to serotypes O59:H19, O102:H6, O174:NM and O174:H21.
      The strains O59:H19 and O174:H21 were positive for the aggR gene. This study
      shows that STEC of different serotypes and genotypes circulate in the city of La
      Plata and surroundings. Despite the genetic diversity observed between the
      O157:H7 isolates, some were indistinguishable by the subtyping techniques used.

PMID- 29336912
TI  - [Bartonella henselae: Serological evidence in pediatric patients with clinical
      suspicion of cat scratch disease].
AB  - Cat scratch disease (CSD) is caused by Bartonella henselae, which mainly affects
      children. The cat is the reservoir. The laboratory diagnosis is based on the
      detection of antibodies by the Indirect Immunofluorescence (IFI) assay. The
      objective of this study was to analyze the serological evidence of B. henselae
      infection in pediatric patients that met the clinical/epidemiological criteria
      for suspected CSD. We studied 92 patients, who were categorized into four
      serological groups: 1) IgG (+)/IgM(+), 31,5% (n=29); 2) IgG (-)/IgM(+), 10,9%
      (n=10); 3) IgG (+)/IgM(-), 9,8% (n=9); 4) IgG (-)/IgM(-), 47,8% (n=44). These
      findings aim to promote future works for investigating the seroprevalence of
      Bartonella spp. in Argentina, which will allow us to know the importance of this
      zoonosis in our population and to evaluate new cut-off points of the technique.

PMID- 29336913
TI  - Erratum to "A systematic review of in-hospital worsening heart failure as an
      endpoint in clinical investigations of therapy for acute heart failure" [Int. J.
      Cardiol. 250 (2018) 215-222].

PMID- 29336915
TI  - Stable coronary artery disease and endothelial progenitor cells.

PMID- 29336914
TI  - Switching from clopidogrel to prasugrel to protect early invasive treatment in
      acute coronary syndromes: Results of the switch over trial.
AB  - BACKGROUND: Clopidogrel is used to pretreat patients with non-ST elevation acute
      coronary syndromes (NSTE-ACS), but prasugrel provides better platelet inhibition
      with improved outcome. However, switching from clopidogrel at the time of
      percutaneous coronary intervention (PCI) remains incompletely defined. Our aim
      was to compare the pharmacodynamic (PD) effects of 3 prasugrel loading doses
      (LDs; G1:10mg, G2: 30mg, and G3: 60mg) before PCI. A fourth group, continuing
      clopidogrel, served as control (G4). METHODS: 100 clopidogrel-pretreated patients
      were enrolled and blood collected before PCI, 30min, 1, 2, 4, 6, 24 and 48h
      thereafter. Platelet inhibition was measured by vasodilator-stimulated
      phosphoprotein phosphorylation (VASP) and Verify-Now assays. The end-points (EP)
      was the difference of PD effect at 4h between G3 and G4 (primary EP) with
      hierarchic evaluation between G2 and G1 versus G4 (secondary EP). A mixed-design
      ANOVA statistic was used to compare the four group scores over time. RESULTS:
      Baseline characteristics were balanced across the groups. Only patients receiving
      60 and 30mg prasugrel LDs showed a rapid (<1h) and significant (p<0.001) platelet
      inhibition up to 48h after PCI.The primary EP was met by G3 (p<0.0001), but also
      G2 scored different (p<0-001) from G4 at 4h after PCI. Similar findings were
      observed with Verify-Now. No differences in 30-day clinical outcomes were
      observed across groups. CONCLUSIONS: Switching NSTE-ACS patients before PCI to
      prasugrel 60 or 30mg LDs determined a better and faster platelet inhibition than
      continuing clopidogrel, while PCI it is still underway.

PMID- 29336916
TI  - The outlook of prognostic indicators for the Takotsubo syndrome.

PMID- 29336917
TI  - Changing Practice Evaluation-Stage 1 Seminoma: Outcomes With Adjuvant Treatment
      Versus Surveillance: Risk Factors for Recurrence and Optimizing Follow-up
      Protocols-Experience From a Supraregional Center.
AB  - BACKGROUND: Stage 1 seminoma is frequently cured by radical orchiectomy; however,
      the management strategies after this diagnosis vary in terms of the use of
      adjuvant treatment and the nature of the follow-up protocols. We analyzed stage 1
      seminomas treated in the Thames Valley Cancer Network for outcomes to determine
      whether any factors are predictive of recurrence. We also studied relapses to
      determine the optimal follow-up schedule and protocol. MATERIALS AND METHODS:
      Data were obtained from centers within the Thames Valley Cancer Network for a 12
      year period from 2004 to 2016. We identified 501 patients with stage 1 seminoma.
      RESULTS: Relapses occurred in 6.2% of the patients receiving adjuvant treatment
      and 6.1% of those who did not. The only statistically significant predictive
      factor identified for relapse was rete testis invasion, and the risk was greater
      when only stromal rete invasion was included, rather than pagetoid as well. A
      trend was seen toward an increased risk with increased tumor size, but the
      difference was not statistically significant. Recurrences developed within the
      first 2 years after surgery in nearly 75% of cases and were identified through
      surveillance computed tomography scans in 54.8% of the patients. All relapses
      were treated curatively. CONCLUSION: Active surveillance leads to excellent
      outcomes for stage 1 seminoma; however, adjuvant treatment should be reserved for
      those with high-risk disease. Follow-up schedules should include computed
      tomography imaging during the first 3 years, long-term measurement of tumor
      markers, and mechanisms for patients to be seen promptly should symptoms of tumor
      recurrence occur.

PMID- 29336918
TI  - Current prevention and control of health care-associated infections in long-term
      care facilities for the elderly in Japan.
AB  - Residents of long-term care facilities for the elderly are vulnerable to health
      care-associated infections. However, compared to medical institutions, long-term
      care facilities for the elderly lag behind in health care-associated infection
      control and prevention. We conducted a epidemiologic study to clarify the current
      status of infection control in long-term care facilities for the elderly in
      Japan. A questionnaire survey on the aspects of infection prevention and control
      was developed according to SHEA/APIC guidelines and was distributed to 617 long
      term care facilities for the elderly in the province of Osaka during November
      2016 and January 2017. The response rate was 16.9%. The incidence rates of health
      care-associated infection outbreaks and residents with health care-associated
      infections were 23.4 per 100 facility-years and 0.18 per 1,000 resident-days,
      respectively. Influenza and acute gastroenteritis were reported most frequently.
      Active surveillance to identify the carrier of multiple drug-resistant organisms
      was not common. The overall compliance with 21 items selected from the SHEA/APIC
      guidelines was approximately 79.2%. All facilities had infection control manuals
      and an assigned infection control professional. The economic burdens of infection
      control were approximately US$ 182.6 per resident-year during fiscal year 2015.
      Importantly, these data implied that physicians and nurses were actively
      contributed to higher SHEA/APIC guideline compliance rates and the advancement of
      infection control measures in long-term care facilities for the elderly. Key
      factors are discussed to further improve the infection control in long-term care
      facilities for the elderly, particularly from economic and social structural
      standpoints.

PMID- 29336919
TI  - Achalasia subtype differences based on clinical symptoms, radiographic findings,
      and stasis scores.

PMID- 29336920
TI  - Pediatric Nurse Practitioners' Perspectives on Health Care Transition From
      Pediatric to Adult Care.
AB  - INTRODUCTION: This study examined the perspectives of pediatric nurse
      practitioners (PNPs) regarding the needs of adolescents, parents/caregivers,
      clinicians, and institutions in the health care transition (HCT) process for
      adolescents/young adults. METHODS: PNPs (N = 170) participated in a luncheon for
      those interested in transition at an annual conference. Small groups discussed
      and recorded their perspectives related to health care transition from adolescent
      to adult services. Content analysis was used to analyze responses (Krippendorff,
      2013). RESULTS: Four themes, Education, Health care system, Support, and
      Communication, emerged from the data analysis. PNPs identified health care
      informatics and adolescents' use of technology as additional critical aspects to
      be considered in health care transition. DISCUSSION: Opportunities and challenges
      identified by the PNPs are discussed to improve the quality and process of
      transitioning adolescents to adult services. This report will help National
      Association of Pediatric Nurse Practitioners formulate a new Health Care
      Transition Policy Statement for the organization.

PMID- 29336921
TI  - Legal and Policy Issues for LGBT Patients with Cancer or at Elevated Risk of
      Cancer.
AB  - OBJECTIVE: To understand the major legal and policy issues for lesbian, gay,
      bisexual and transgender (LGBT) cancer patients. DATA SOURCES: LGBT health policy
      research. CONCLUSION: Major policy issues include discrimination, lack of
      cultural competency and clinically appropriate care, insurance coverage, family
      recognition, and sexual orientation and gender identity data collection.
      IMPLICATIONS FOR NURSING PRACTICE: Nurses play a major role in providing
      affirming and competent care to LGBT cancer patients. Using correct names and
      pronouns with transgender patients, and collecting sexual orientation and gender
      identity data can send an affirming message to LGBT patients, as well as inform
      decision support and preventive screenings, and improve treatment outcomes.

PMID- 29336922
TI  - Segmentation-free direct tumor volume and metabolic activity estimation from PET
      scans.
AB  - Tumor volume and metabolic activity are two robust imaging biomarkers for
      predicting early therapy response in F-fluorodeoxyglucose (FDG) positron emission
      tomography (PET), which is a modality to image the distribution of radiotracers
      and thereby observe functional processes in the body. To date, estimation of
      these two biomarkers requires a lesion segmentation step. While the segmentation
      methods requiring extensive user interaction have obvious limitations in terms of
      time and reproducibility, automatically estimating activity from segmentation,
      which involves integrating intensity values over the volume is also suboptimal,
      since PET is an inherently noisy modality. Although many semi-automatic
      segmentation based methods have been developed, in this paper, we introduce a
      method which completely eliminates the segmentation step and directly estimates
      the volume and activity of the lesions. We trained two parallel ensemble models
      using locally extracted 3D patches from phantom images to estimate the activity
      and volume, which are derivatives of other important quantification metrics such
      as standardized uptake value (SUV) and total lesion glycolysis (TLG). For
      validation, we used 54 clinical images from the QIN Head and Neck collection on
      The Cancer Imaging Archive, as well as a set of 55 PET scans of the Elliptical
      Lung-Spine Body PhantomTMwith different levels of noise, four different
      reconstruction methods, and three different background activities, namely; air,
      water, and hot background. In the validation on phantom images, we achieved
      relative absolute error (RAE) of 5.11 % +/-3.5% and 5.7 % +/-5.25% for volume and
      activity estimation, respectively, which represents improvements of over 20% and
      6% respectively, compared with the best competing methods. From the validation
      performed using clinical images, we found that the proposed method is capable of
      obtaining almost the same level of agreement with a group of trained experts, as
      a single trained expert is, indicating that the method has the potential to be a
      useful tool in clinical practice.

PMID- 29336924
TI  - Immunization of preterm infants with GSK's hexavalent combined diphtheria-tetanus
      acellular pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae
      type b conjugate vaccine: A review of safety and immunogenicity.
AB  - BACKGROUND: Infants with history of prematurity (<37 weeks gestation) and low
      birth weight (LBW, <2500 g) are at high risk of infection due to functional
      immaturity of normal physical and immunological defense mechanisms. Despite
      current recommendations that infants with history of prematurity/LBW should
      receive routine immunization according to the same schedule and chronological age
      as full-term infants, immunization is often delayed. METHODS: Here we summarize
      10 clinical studies and 15 years of post-marketing safety surveillance of GSK's
      hexavalent vaccine (DTPa-HBV-IPV/Hib), a combined diphtheria-tetanus-acellular
      pertussis-hepatitis-B-inactivated-poliovirus-Haemophilus influenzae-type-b (Hib)
      conjugate vaccine, when administered alone, or co-administered with pneumococcal
      conjugate, rotavirus, and meningococcal vaccines and respiratory syncytial virus
      IgG to infants with history of prematurity/LBW in clinical trials. RESULTS: At
      least 92.5% of infants with history of prematurity/LBW as young as 24 weeks
      gestation in clinical studies were seropositive to all vaccine antigens after 3
      dose primary vaccination with GSK's hexavalent DTPa-HBV-IPV/Hib vaccine, with
      robust immune responses to booster vaccination. Seropositivity rates and antibody
      concentrations to hepatitis B and Hib appeared lower in infants with history of
      prematurity/LBW than term infants. Between 13-30% of medically stable infants
      with history of prematurity developed apnea after vaccination with GSK's
      hexavalent DTPa-HBV-IPV/Hib vaccine; usually after dose 1. The occurrence of post
      immunization cardiorespiratory events appears to be influenced by the severity of
      any underlying neonatal condition. Most cardiorespiratory events resolve
      spontaneously or require minimal intervention. GSK's hexavalent DTPa-HBV-IPV/Hib
      vaccine was well tolerated in co-administration regimens. CONCLUSION: GSK's
      hexavalent DTPa-HBV-IPV/Hib vaccine alone or co-administered with other pediatric
      vaccines has a clinically acceptable safety and immunogenicity profile when used
      in infants with history of prematurity/LBW for primary and booster vaccination.
      Additional studies are needed in very premature and very LBW infants. However,
      currently available data support using GSK's hexavalent DTPa-HBV-IPV/Hib vaccine
      to immunize infants with history of prematurity/LBW according to chronological
      age.

PMID- 29336923
TI  - Report on WHO meeting on immunization in older adults: Geneva, Switzerland, 22-23
      March 2017.
AB  - Many industrialized countries have implemented routine immunization policies for
      older adults, but similar strategies have not been widely implemented in low- and
      middle-income countries (LMICs). In March 2017, the World Health Organization
      (WHO) convened a meeting to identify policies and activities to promote access to
      vaccination of older adults, specifically in LMICs. Participants included
      academic and industry researchers, funders, civil society organizations,
      implementers of global health interventions, and stakeholders from developing
      countries with adult immunization needs. These experts reviewed vaccine
      performance in older adults, the anticipated impact of adult vaccination
      programs, and the challenges and opportunities of building or strengthening an
      adult and older adult immunization platforms. Key conclusions of the meeting were
      that there is a need for discussion of new opportunities for vaccination of all
      adults as well as for vaccination of older adults, as reflected in the recent
      shift by WHO to a life-course approach to immunization; that immunization in
      adults should be viewed in the context of a much broader model based on an
      individual's abilities rather than chronological age; and that immunization
      beyond infancy is a global priority that can be successfully integrated with
      other interventions to promote healthy ageing. As WHO is looking ahead to a
      global Decade of Healthy Ageing starting in 2020, it will seek to define a
      roadmap for interdisciplinary collaborations to integrate immunization with
      improving access to preventive and other healthcare interventions for adults
      worldwide.

PMID- 29336926
TI  - Changes of Tumour-Node-Metastasis Staging in 2017: Concepts and Evolutions in the
      European and American Continents.

PMID- 29336925
TI  - A novel inactivated vaccine against Lawsonia intracellularis induces rapid
      induction of humoral immunity, reduction of bacterial shedding and provides
      robust gut barrier function.
AB  - Porcine proliferative ileitis is a major economic burden for the swine industry,
      affecting growing pigs and young adult pigs. In this study, the protective
      efficacy of an inactivated, injectable whole-cell bacteria vaccine against L.
      intracellularis - Porcilis(r) Ileitis was evaluated under field conditions.
      Eighty-five, three-week-old pigs on a commercial farrow-to-finish farm were
      vaccinated by the intramuscular route, either with a dose of injectable vaccine,
      or with saline. A subset of vaccinates and control pigs were necropsied at 21
      days post-challenge. Incidence and severity of ileitis were evaluated by gross
      and microscopic observation of ileal tissues. Colonization of the gut after
      challenge was examined by L. intracellularis-specific immunohistochemistry, and
      qPCR of ileal scrapings. Integrity of the intestinal barrier was evaluated to
      quantify a range of intestinal markers including secreted mucin and intestinal
      alkaline phosphatase, and innate immune markers including Caspase-3 and
      Calprotectin. A second subset of pigs was monitored for fecal shedding of L.
      intracellularis, until resolution of shedding. Our investigation indicated that
      Porcilis Ileitis provided robust protection against ileitis, reduced bacterial
      shedding 15-fold (p < .05) and preserved normal gut barrier function in the face
      of an experimental challenge with virulent L. intracellularis.

PMID- 29336927
TI  - Efficacy and Safety of Sacral and Percutaneous Tibial Neuromodulation in Non
      neurogenic Lower Urinary Tract Dysfunction and Chronic Pelvic Pain: A Systematic
      Review of the Literature.
AB  - CONTEXT: Neuromodulation is considered in patients with non-neurogenic lower
      urinary tract dysfunction (LUTD) not responsive to conservative treatment.
      OBJECTIVE: To systematically review the available studies on efficacy and safety
      of sacral neuromodulation (SNM) and percutaneous tibial nerve stimulation (PTNS)
      in non-neurogenic LUTDs not responsive to conservative treatments. EVIDENCE
      ACQUISITION: A literature research was conducted in PubMed/Medline and Scopus,
      restricted to articles in English, published between January 1998 and June 2017,
      with at least 20 patients and 6 mo of follow-up. EVIDENCE SYNTHESIS: Twenty-one
      reports were identified. Concerning SNM, the improvement of >=50% in leakage
      episodes ranged widely between 29% and 76%. Overall dry rate ranged between 43%
      and 56%. Overall success/improvement rate in PTNS varied between 54% and 59%.
      Symptom improvement or efficacy in interstitial cystitis/bladder pain syndrome
      patients appeared to be lower compared with other indications in both techniques.
      Safety data showed fewer side effects in patients submitted to PTNS. CONCLUSIONS:
      Neuromodulation gives good results and is a safe therapy for patients with
      overactive bladder or chronic nonobstructive urinary retention with long-lasting
      efficacy. Moreover, PTNS has been shown to have good success rates and fewer side
      effects compared with SNM. These data have to be confirmed with long-term follow
      up. PATIENT SUMMARY: Sacral neuromodulation can improve low urinary tract
      symptoms in selected patients; it appears to be a safe therapy for nonresponders
      to standard medical therapies. Percutaneous tibial nerve stimulation (PTNS) is a
      less invasive technique that gives good results in short time with fewer side
      effects. However, we must consider that PTNS has not been tested in the long term
      and results are lower if compared with SNM.

PMID- 29336928
TI  - Tackling the recurrence of Clostridium difficile infection.
AB  - The pathogenesis of recurrent Clostridium difficile infection (CDI) is still
      poorly understood. The risk of recurrence is approximately 20% after an initial
      CDI episode and dramatically increases with subsequent CDI recurrences. Several
      factors may play a role in recurrent CDI (rCDI), including conditions influencing
      germination, metabolic pathways that influence toxin production of C. difficile,
      and the microbiota composition offering protection against colonization and
      disease caused by C. difficile. Paradoxically, the currently recommended
      treatment for acute symptomatic CDI, i.e. metronidazole or vancomycin, can cause
      modification of the intestinal flora. Indeed, administration of anti-CDI
      antibiotics leads to suppression of C. difficile, along with collateral damage of
      the protective intestinal microbiota and opening of a "window of vulnerability"
      for recurrence. Host factors also have a prominent role, including innate and
      acquired humoral immunity, i.e. passive antibodies administration or active
      vaccination as a prevention strategy. They play a crucial role in the protection
      against severe and recurrent CDI. The assessment of risk factors of recurrence
      and modeling prediction scores could help in preventing the troublesome
      experience of CDI recurrence. Six studies have methodologically assessed
      prediction scores for rCDI. However, the definition of recurrence was
      heterogeneous, external validation was often not performed, and immunological
      factors were often not considered. There is a need for further studies on the
      pathophysiology of recurrence to design models for prediction that are sound and
      applicable in clinical practice.

PMID- 29336929
TI  - Economic burden and cost-effective management of Clostridium difficile
      infections.
AB  - Clostridium difficile infection (CDI) is the most important cause of healthcare
      associated infectious diarrhea in industrialized countries. We performed a
      literature review of the overall economic burden of initial and recurrent CDI as
      well as of the cost-effectiveness of the various treatment strategies applied in
      these settings. Even though analysis of health economic data is complicated by
      the limited comparability of results, our review identified several
      internationally consistent results. Authors from different countries have shown
      that recurrent CDI disproportionally contributes to the overall economic burden
      of CDI and therefore offers considerable saving potential. Subsequent cost
      effectiveness analyses almost exclusively identified fidaxomicin as the preferred
      treatment option for initial CDI and fecal microbiota transplant (FMT) for
      recurrent CDI. Among the various FMT protocols, optimum results were obtained
      using early colonoscopy-based FMT.

PMID- 29336930
TI  - Exploring ways to improve CDI outcomes.
AB  - Clostridium difficile is an anaerobic spore-forming Gram-positive bacillus
      recognized as an evolving international health problem. Metronidazole and
      vancomycin were - until recently - the only drugs available to treat C. difficile
      infection (CDI). Better knowledge of the pathophysiology and the development of
      new drugs completely modified the management of initial episodes and recurrences
      of CDI. Fidaxomicin significantly reduced recurrences compared with vancomycin.
      New drugs are also currently evaluated (cadazolid, surotomycin, ridinilazole,
      rifaximin). Gut microbiota homeostasis was clearly shown to be a key determinant
      in recurrences as demonstrated by the development of gut microbiota
      transplantation and alternative microbiota substitution. Passive immunotherapy
      and vaccinal approaches are also currently being evaluated. In conclusion, CDI
      treatment has evolved with the development of new therapeutic pathways which now
      need to be implemented in international guidelines.

PMID- 29336931
TI  - Impact of crack cocaine use on the occurrence of oral lesions and micronuclei.
AB  - The aim of this study was to investigate the occurrence of oral lesions and
      micronuclei in crack cocaine users. A cross-sectional study was conducted
      involving 106 crack users and 106 non-users matched for age, sex, and tobacco
      use. Socio-demographic characteristics, the consumption of psychoactive
      substances, and the occurrence of fundamental lesions were investigated. Cellular
      changes in the oral mucosa (karyolysis, karyorrhexis, 'broken egg' events, and
      micronuclei) were determined by exfoliative cytology for 54 participants in each
      group. Crack users had a greater occurrence of fundamental lesions (P=0.001).
      Furthermore, they had higher mean occurrences of micronuclei (17.25 vs. 3.80),
      karyolysis (12.39 vs. 9.46), and karyorrhexis (30.39 vs. 10.11) (number per 1000
      cells) than non-users (all P<0.05). No difference between the groups was found
      with regard to broken egg events (P>0.05). After controlling for confounding
      variables, fundamental lesions were 2.02-fold more frequent and micronuclei were
      3.54-fold more frequent in crack users. Crack use was found to be associated with
      clinical and cellular changes in the oral mucosa. These findings can contribute
      to the planning of health care for individuals who are dependent on street drugs.

PMID- 29336932
TI  - Orthognathic surgery in Melnick-Needles syndrome: a review of the literature and
      report of two siblings.
AB  - Melnick-Needles syndrome (MNS) is a rare congenital X-linked dominant skeletal
      dysplasia, characterized by exophthalmos, a prominent forehead, and mandibular
      hypoplasia and retrognathism. Dental features may include anodontia, hypodontia,
      or oligodontia. Increased collagen content, unpredictable collagen synthesis, and
      abnormal bony architecture have raised concerns regarding bone splitting
      intraoperatively and bone healing postoperatively. This report describes the
      cases of two sisters with MNS, who successfully underwent orthognathic surgery
      consisting of bilateral mandibular ramus osteotomies combined with advancement
      genioplasty and iliac crest bone grafting, to correct the classical MNS facial
      deformity of mandibular retrognathia.

PMID- 29336933
TI  - Left vocal cord paralysis after patent ductus arteriosus ligation: A systematic
      review.
AB  - CONTEXT: Extremely premature (EP) infants are at increased risk of left vocal
      cord paralysis (LVCP) following surgery for patent ductus arteriosus (PDA).
      OBJECTIVE: A Systematical Review was conducted to investigate the incidence and
      outcomes of LVCP after PDA ligation in EP born infants. DATA SOURCES: Searches
      were performed in Cochrane, Medline, Embase, Cinahl and PsycInfo. STUDY
      SELECTION: Studies describing EP infants undergoing PDA surgery and reporting
      incidence of LVCP were included. DATA EXTRACTION AND SYNTHESIS: Study details,
      demographics, incidence of LVCP, diagnostic method and reported outcomes were
      extracted. DerSimonian and Laird random effect models with inverse variance
      weighting were used for all analyses. STUDY APPRAISAL: The Newcastle-Ottawa scale
      for observational studies was used for quality assessment. RESULTS: 21
      publications including 2067 infants were studied. The overall pooled summary
      estimate of LVCP incidence was 9.0% (95% CI 5.0, 15.0). However, the pooled
      incidence increased to 32% when only infants examined with laryngoscopy were
      included. The overall risk ratio for negative outcomes was higher in the LVCP
      group (2.20, 95% CI 1.69, 2.88, p = 0.01) compared to the non-LVCP-group.
      CONCLUSIONS: Reported incidence of LVCP varies widely. This may be explained by
      differences in study designs and lack of routine vocal cords postoperative
      assessment. LVCP is associated with negative outcomes in EP infants. The
      understanding of long-term outcomes is scarce. Routine laryngoscopy may be
      necessary to identify all cases of LVCP, and to provide correct handling for
      infants with LVCP.

PMID- 29336934
TI  - Determination of recombination and polarity correction factors, kS and kP, for
      small cylindrical ionization chambers PTW 31021 and PTW 31022 in pulsed filtered
      and unfiltered beams.
AB  - The aim of this technical communication is to provide correction factors for
      recombination and polarity effect for two new ionization chambers PTW PinPoint 3D
      (type 31022) and PTW Semiflex 3D (type 31021). The correction factors provided
      are for the (based on the) German DIN 6800-2 dosimetry protocol and the AAPM TG51
      protocol. The measurements were made in filtered and unfiltered high-energy
      photon beams in a water equivalent phantom at maximum depth of the PDD and a
      field size on the surface of 10cm*10cm. The design of the new chamber types leads
      to an ion collection efficiency and a polarity effect that are well within the
      specifications requested by pertinent dosimetry protocols including the addendum
      of TG-51. It was confirmed that the recombination effect of both chambers mainly
      depends on dose per pulse and is independent of the filtration of the photon
      beam.

PMID- 29336935
TI  - Update on the laboratory investigation of dyslipidemias.
AB  - The role of the clinical laboratory is evolving to provide more information to
      clinicians to assess cardiovascular disease (CVD) risk and target therapy more
      effectively. Current routine methods to measure LDL-cholesterol (LDL-C), the
      Friedewald calculation, ultracentrifugation, electrophoresis and homogeneous
      direct methods have established limitations. Studies suggest that LDL and HDL
      size or particle concentration are alternative methods to predict future CVD
      risk. At this time there is no consensus role for lipoprotein particle or
      subclasses in CVD risk assessment. LDL and HDL particle concentration are
      measured by several methods, namely gradient gel electrophoresis,
      ultracentrifugation-vertical auto profile, nuclear magnetic resonance and ion
      mobility. It has been suggested that HDL functional assays may be better
      predictors of CVD risk. To assess the issue of lipoprotein subclasses/particles
      and HDL function as potential CVD risk markers robust, simple, validated
      analytical methods are required. In patients with small dense LDL particles, even
      a perfect measure of LDL-C will not reflect LDL particle concentration. Non-HDL-C
      is an alternative measurement and includes VLDL and CM remnant cholesterol and
      LDL-C. However, apolipoprotein B measurement may more accurately reflect LDL
      particle numbers. Non-fasting lipid measurements have many practical advantages.
      Defining thresholds for treatment with new measurements of CVD risk remain a
      challenge. In families with genetic variants, ApoCIII and lipoprotein (a) may be
      additional risk factors. Recognition of familial causes of dyslipidemias and
      diagnosis in childhood will result in early treatment. This review discusses the
      limitations in current laboratory technologies to predict CVD risk and reviews
      the evidence for emergent approaches using newer biomarkers in clinical practice.

PMID- 29336936
TI  - Very unusual "needle- and pencil-like" uric acid crystals in the urine unmasked
      by infrared spectroscopy investigation.
AB  - In this paper we describe a case with very unusual "needle- and pencil-like"
      crystals, partly similar to those reported by other investigators, who considered
      them as due to uric acid. Quite importantly, infrared spectroscopy investigation
      which, to our knowledge, we have been the first to perform on this type of
      crystals, confirmed their nature as uric acid structures. This case demonstrates
      that the planet of urinary crystals still has several unknown facets and still
      deserves exploration.

PMID- 29336937
TI  - The combination of stereo-EEG and radiofrequency ablation.
AB  - SEEG-guided radiofrequency thermocoagulation (SEEG-guided RFTC), a combination of
      Stereo-electroencephalography (SEEG) and radiofrequency thermocoagulation (RFTC),
      has been performed since 2001 in drug resistant epilepsy. The interest of this
      procedure is to aim at total or partial destruction of the epileptogenic zone, as
      tailored in each individual patient by the SEEG exploration. These multiple SEEG
      guided RFTC lesions of epileptic foci are produced by using a radiofrequency
      generator connected to the electrode contacts. This review summarizes the results
      of SEEG-guided RFTC reported in 251 patients. This procedure appears to be safe
      since complications are rare, minor and usually reversible, which is explained by
      the use of functional electrical stimulations before RFTC. It makes it also
      possible to produce RF lesions located very close to cortical areas having a high
      functional value or being poorly accessible to a conventional surgical procedure.
      Even if seizure outcome is not as good as results of surgery, 41% of the patients
      are responders at 12 months with several seizure free patients. The benefit-risk
      ratio of the SEEG-guided RFTC procedure proved to be particularly favorable for
      the patients presenting with epileptogenic cortical malformation of development
      (nodular heterotopy as well as focal cortical dysplasia) and for those in whom
      surgery is not feasible or risky. For the patients in whom surgery is feasible,
      SEEG-guided RFTC could be used as a first step, as a predictive therapeutic test
      before resective surgery.

PMID- 29336938
TI  - Determination of the energy requirements in mechanically ventilated critically
      ill elderly patients in different BMI groups using the Harris-Benedict equation.
AB  - BACKGROUND: Due to studies on calorie requirement in mechanically ventilated
      critically ill elderly patients are few, and indirect calorimetry (IC) is not
      available in every intensive care unit (ICU). The aim of this study was to
      compare IC and Harris-Benedict (HB) predictive equation in different BMI groups.
      METHODS: A total of 177 mechanically ventilated critically ill elderly patients
      (?65 years old) underwent IC for measured resting energy expenditure (MREE).
      Estimated calorie requirement was calculated by the HB equation, using actual
      body weight (ABW) and ideal body weight (IBW) separately. Patients were divided
      into four BMI groups. One-way ANOVA and Pearson's correlation coefficient were
      used for statistical analyses. RESULTS: The mean MREE was 1443.6 +/- 318.2
      kcal/day, HB(ABW) was 1110.9 +/- 177.0 kcal/day and HB(IBW) was 1101.5 +/- 113.1
      kcal/day. The stress factor (SFA = MREE / HB(ABW)) was 1.43 +/- 0.26 for the
      underweight, 1.30 +/- 0.27 for the normal weight, 1.20 +/- 0.19 for the
      overweight, and 1.20 +/- 0.31 for the obese. The SFI (SFI = MREE / HB(IBW)) was
      1.24 +/- 0.24 for the underweight, 1.31 +/- 0.26 for the normal weight, 1.36 +/-
      0.21 for the overweight, and 1.52 +/- 0.39 for the obese. MREE had significant
      correlation both with REE(ABW) = HB(ABW) * SFA (r = 0.46; P < 0.0001) and
      REE(IBW) = HB(IBW) * SFI (r = 0.43; P < 0.0001). CONCLUSION: IC is the best
      accurate method for assessing calorie requirement of mechanically ventilated
      critically ill elderly patients. When IC is not available, using the predictive
      HB equation is an alternative choice. Calorie requirement can be predicted by
      HB(ABW) * 1.20-1.43 for critically ill elderly patients according to different
      BMI groups, or using HB(IBW) * 1.24-1.52 for patients with edema, ascites or no
      available body weight data.

PMID- 29336939
TI  - Examination of serum hematinics and autoantibodies is important for treatment of
      recurrent aphthous stomatitis.

PMID- 29336940
TI  - Myeloperoxidase: Its role for host defense, inflammation, and neutrophil
      function.
AB  - Myeloperoxidase (MPO) is a heme-containing peroxidase expressed mainly in
      neutrophils and to a lesser degree in monocytes. In the presence of hydrogen
      peroxide and halides, MPO catalyzes the formation of reactive oxygen
      intermediates, including hypochlorous acid (HOCl). The MPO/HOCl system plays an
      important role in microbial killing by neutrophils. In addition, MPO has been
      demonstrated to be a local mediator of tissue damage and the resulting
      inflammation in various inflammatory diseases. These findings have implicated MPO
      as an important therapeutic target in the treatment of inflammatory conditions.
      In contrast to its injurious effects at sites of inflammation, recent studies
      using animal models of various inflammatory diseases have demonstrated that MPO
      deficiency results in the exaggeration of inflammatory response, and that it
      affects neutrophil functions including cytokine production. Given these diverse
      effects, a growing interest has emerged in the role of this well-studied enzyme
      in health and disease.

PMID- 29336941
TI  - Age-specific excess mortality patterns and transmissibility during the 1889-1890
      influenza pandemic in Madrid, Spain.
AB  - PURPOSE: Although the 1889-1890 influenza pandemic was one of the most important
      epidemic events of the 19th century, little is known about the mortality impact
      of this pandemic based on detailed respiratory mortality data sets. METHODS: We
      estimated excess mortality rates for the 1889-1890 pandemic in Madrid from high
      resolution respiratory and all-cause individual-level mortality data retrieved
      from the Gazeta de Madrid, the Official Bulletin of the Spanish government. We
      also generated estimates of the reproduction number from the early growth phase
      of the pandemic. RESULTS: The main pandemic wave in Madrid was evident from
      respiratory and all-cause mortality rates during the winter of 1889-1890. Our
      estimates of excess mortality for this pandemic were 58.3 per 10,000 for all
      cause mortality and 44.5 per 10,000 for respiratory mortality. Age-specific
      excess mortality rates displayed a J-shape pattern, with school children aged 5
      14 years experiencing the lowest respiratory excess death rates (8.8 excess
      respiratory deaths per 10,000), whereas older populations aged greater than or
      equal to 70 years had the highest rates (367.9 per 10,000). Although seniors
      experienced the highest absolute excess death rates, the standardized mortality
      ratio was highest among young adults aged 15-24 years. The early growth phase of
      the pandemic displayed dynamics consistent with an exponentially growing
      transmission process. Using the generalized-growth method, we estimated the
      reproduction number in the range of 1.2-1.3 assuming a 3-day mean generation
      interval and of 1.3-1.5 assuming a 4-day mean generation interval. CONCLUSIONS:
      Our study adds to our understanding of the mortality impact and transmissibility
      of the 1889-1890 influenza pandemic using detailed individual-level mortality
      data sets. More quantitative studies are needed to quantify the variability of
      the mortality impact of this understudied pandemic at regional and global scales.

PMID- 29336942
TI  - Malleable Penile Implant Is an Effective Therapeutic Option in Men With
      Peyronie's Disease and Erectile Dysfunction.
AB  - BACKGROUND: The inflatable penile prosthesis (IPP) is typically the preferred
      implant for Peyronie's disease (PD) and malleable penile prostheses (MPPs) have
      been discouraged. AIMS: To evaluate the effectiveness and patient satisfaction of
      the MPP vs IPP in patients with PD. METHODS: Men with PD and erectile dysfunction
      who elected for penile implant surgery constituted the study population.
      Preoperatively, demographic and comorbidity parameters were recorded. Curvature
      was measured with a goniometer at maximum rigidity after intracavernosal
      injection of a vasoactive agent. Postoperatively, overall satisfaction was
      measured at 3, 6, 12, and 24 months on 5-point Likert scale from 1 (dissatisfied)
      to 5 (very satisfied). RESULTS: 166 men with a mean age of 59 +/- 10 years were
      analyzed. The mean preoperative curvature in the entire cohort was 65 degrees 
      (range = 30-130 degrees ). 94% of patients with MPP had total resolution of their
      curvature at the end of the operation, whereas 8 patients (6%) had residual
      curvature (25-40 degrees ). In the IPP group 25 of 30 (83.3%) had a straight
      penis at the end of surgery, whereas 5 of 30 (16.7%) had residual curvature, with
      the mean magnitude being 33 degrees  in the MPP group and 30 degrees  in the IPP
      group. 86% of all patients had diabetes. There were no differences between the 2
      implant groups in age, hemoglobin A1c, body mass index, or smoking status. The
      mean patient satisfaction was 4.42 +/- 0.70 (range = 2-5) and there was no
      difference between the 2 groups. The mean follow-up period was 23.4 months (range
      = 6-29 months). CONCLUSION: We found that the MPP is as effective as the IPP in
      curvature correction in patients with PD, with similar patient satisfaction for
      the 2 groups. Habous M, Farag M, Tealab A, et al. Malleable Penile Implant Is an
      Effective Therapeutic Option in Men With Peyronie's Disease and Erectile
      Dysfunction. Sex Med 2018;6:24-29.

PMID- 29336943
TI  - One time quantitative PCR detection of Pseudomonas aeruginosa to discriminate
      intermittent from chronic infection in cystic fibrosis.
AB  - BACKGROUND: Chronic airway infection with Pseudomonas aeruginosa is a major risk
      factor of progression of lung disease in patients with cystic fibrosis (CF).
      Chronic P. aeruginosa infection evolves from intermittent infection that is
      amenable to antibiotic eradication, whereas chronically adapted P. aeruginosa
      becomes resistant to antibiotic therapy. Discrimination of intermittent versus
      chronic infection is therefore of high therapeutic relevance, yet the available
      diagnostic methods are only partly satisfactory. The aim of the present study
      was, therefore, to evaluate the usage of quantitative PCR (qPCR) to measure
      pathogen abundance and to discriminate between intermittent and chronic
      Pseudomonas infection in patients with CF. METHOD: Using an established qPCR
      protocol, we analyzed the abundance of P. aeruginosa in 141 throats swabs and 238
      sputa from CF patients with intermittent or chronic infection with P. aeruginosa,
      as determined by standard culture based diagnostics. RESULTS: We observed a large
      increase of abundance of P. aeruginosa in throat swabs and sputum samples from
      patients with chronic compared to intermittent infections with P. aeruginosa. The
      data show that abundance of P. aeruginosa as measured by qPCR is a valuable tool
      to discriminate intermittent from chronic infection. Of note, P. aeruginosa
      burden seems more sensitive than mucoidity phenotype to discriminate chronic from
      intermittent strains. Furthermore we observed that molecular detection in throat
      swabs was linked to a viable culture in the sputum when sputum was available.
      This result is of special interest in young patients with cystic fibrosis that
      often cannot expectorate sputum. We also observed that qPCR in comparison to
      culture detected the infection earlier. CONCLUSION: The results suggest that qPCR
      detection and quantification of P. aeruginosa is a precious tool to be added to
      the diagnostic toolbox in cystic fibrosis.

PMID- 29336944
TI  - Editorial commentary: Newborn screening for Fabry disease: Too much too soon?

PMID- 29336945
TI  - Current treatment of significant left main coronary artery disease: A review.
AB  - Though infrequent, left main stenosis has a major prognostic impact. The
      management of left main disease has evolved over the last few decades with the
      growing evidence of the efficacy and safety of percutaneous interventions, as
      attested by the most recent trials. However, mastery of the technical aspects of
      left main bifurcation stenting is essential in ensuring optimal results. This
      review focuses on recent data concerning left main angioplasty results as well as
      the current technical approaches.

PMID- 29336946
TI  - LDL cholesterol: How low to go?
AB  - Epidemiology and the results of large-scale outcome trials indicate that the
      association of LDL with atherosclerotic cardiovascular disease is causal, and
      continuous not only across levels seen in the general population but also down to
      sub-physiological values. There is no scientific basis, therefore, to set a
      target or 'floor' for LDL cholesterol lowering, and this presents a clinical and
      conceptual dilemma for prescribers, patients, and payers. With the advent of
      powerful agents such as proprotein convertase/subtilisin kexin type 9 (PCSK9)
      inhibitors, LDL cholesterol can be lowered profoundly but health economic
      constraints mandate that this therapeutic approach needs to be selective. Based
      on the need to maximize the absolute risk reduction when prescribing combination
      lipid-lowering therapy, it is appropriate to prioritize patients with the highest
      risk (aggressive and established CVD) who will obtain the highest benefit, that
      is, those with elevated LDL cholesterol on optimized statin therapy.

PMID- 29336947
TI  - Characterization of goose SPMS: Molecular characterization and expression
      profiling of SPMS in the goose ovary.
AB  - Spermine synthase (SPMS), which converts spermidine into spermine, is essential
      for normal cell growth and development processes in humans and other mammals, but
      the molecular characterization and expression profiling of the SPMS gene remain
      undetermined in goose tissues and ovarian follicles. In this study, the SPMS cDNA
      sequence of the Sichuan white goose was cloned and analysed, and SPMS mRNA
      expression was profiled in various tissues and ovarian follicles. The results
      showed that the open reading frame of the SPMS cDNA sequence was 1092 bp in
      length, encoding 363 amino acids with a molecular weight of 41 kDa. Among all the
      examined tissues, SPMS expression was highest in the spleen and cerebrum and
      lowest in the breast and thigh muscles. SPMS expression in the F1 follicle was
      significantly higher than that in the POF (except for POF2) (P < 0.05). Our
      results indicate that SPMS might play an important role in follicular development
      and ovulation.

PMID- 29336948
TI  - The effect of a potentially tamper-resistant oxycodone formulation on opioid use
      and harm: main findings of the National Opioid Medications Abuse Deterrence
      (NOMAD) study.
AB  - BACKGROUND: Escalation of pharmaceutical opioid use and harm in North America is
      well-documented, with similar issues emerging in Australia. One response is the
      development of tamper-resistant formulations of opioids. A potentially tamper
      resistant formulation of controlled-release oxycodone was introduced in Australia
      in April, 2014, rapidly replacing the non-tamper-resistant formulation. Our study
      is the most systematic and comprehensive examination of the impact of a new
      opioid formulation to date, assessing the effect of tamper-resistant formulation
      of controlled-release oxycodone on population-level opioid use and opioid-related
      harm (ie, overdose, help-seeking, and treatment-seeking); and opioid use,
      tampering, and preference for the tamper-resistant formulation of controlled
      release oxycodone compared with other drugs or formulations among sentinel
      populations likely to tamper with pharmaceutical opioids. METHODS: We conducted
      interrupted time-series analyses of opioid sales data and multiple routinely
      collected health datasets, followed up a cohort of people who tamper with
      pharmaceutical opioids before and after the introduction of the tamper-resistant
      formulation of controlled-release oxycodone, and analysed annual surveys of
      people who inject drugs. Data were collected from several Australian states: New
      South Wales, South Australia, and Tasmania. Meta-analyses (weighted Z tests) were
      conducted to synthesise across data sources providing evidence for a given
      indicator. FINDINGS: At the population level, we found reduced sales of higher
      strengths of controlled-release oxycodone and increased sales of other oxycodone
      formulations. No significant effect was observed among population-level
      indicators of opioid overdose, or help or treatment-seeking. Mortality data were
      not available for inclusion at the time of our study. Meta-analyses across
      sentinel populations (ie, prospective cohort, surveys of people who inject drugs,
      and clients of supervised injecting facilities or needle and syringe programmes)
      indicated reduced controlled-release oxycodone use via tampering (mainly
      injection), with no evidence of switching to heroin or other drug use.
      INTERPRETATION: This formulation of controlled-release oxycodone reduced
      tampering with pharmaceutical opioids among people who inject drugs, but did not
      affect population-level opioid use or harm. FUNDING: Mundipharma Australia, the
      Australian Government, and the National Health and Medical Research Council.

PMID- 29336949
TI  - Evaluating difficult-to-crush opioids in the community.

PMID- 29336950
TI  - Daratumumab: Therapeutic asset, biological trap!
AB  - OBJECTIVES: Recently, daratumumab has been included in the therapeutic strategies
      for myeloma patients. This molecule is an antibody directed against CD38,
      strongly expressed on plasma cells. Nevertheless, as CD38 is also present on
      erythrocyte membrane, daratumumab interferes with immunohaematological tests,
      complicating the selection of compatible blood. METHODS: A total of 14 patients
      treated by daratumumab have been followed in our transfusion laboratory. Among
      them, 11 have been transfused. Dithiotreitol (DTT) has been used to inhibit the
      daratumumab's interference, in the pre-transfusion tests (irregular antibody
      screening and cross-match). RESULTS: The red blood cell treatment with DTT has
      been very efficacious to inhibit the daratumumab's interference in 13 patients
      out of 14. Some precautionary measures had to be taken into account, especially
      the pH and the storage conditions. An extended pheno/genotype was an additional
      security element in the selection of compatible blood. To simplify and to
      optimize the laboratory practices, a decisional flow chart has been written.
      CONCLUSION: DTT red blood cell treatment is very useful and efficacious in the
      pre-transfusion tests of patients treated with daratumumab. It allows to avoid
      the selection of blood bags only on the basis of an extended pheno/genotype, what
      is more secure and more ethical with respect to other at higher risk patients. A
      clear decisional flow chart allows a quality assurance gait. Collaboration with
      physicians is essential.

PMID- 29336952
TI  - The Safe Use of Medication by Adolescents Living on Campus.

PMID- 29336951
TI  - Design, synthesis and evaluation against Chikungunya virus of novel small
      molecule antiviral agents.
AB  - Chikungunya virus is a re-emerging arbovirus transmitted to humans by mosquitoes,
      responsible for an acute flu-like illness associated with debilitating
      arthralgia, which can persist for several months or become chronic. In recent
      years, this viral infection has spread worldwide with a previously unknown
      virulence. To date, no specific antivirals treatments nor vaccines are available
      against this important pathogen. Starting from the structures of two antiviral
      hits previously identified in our research group with in silico techniques, this
      work describes the design and preparation of 31 novel structural analogues, with
      which different pharmacophoric features of the two hits have been explored and
      correlated with the inhibition of Chikungunya virus replication in cells.
      Structure-activity relationships were elucidated for the original scaffolds, and
      different novel antiviral compounds with EC50 values in the low micromolar range
      were identified. This work provides the foundation for further investigation of
      these promising novel structures as antiviral agents against Chikungunya virus.

PMID- 29336953
TI  - Effective use of iron-aluminum rich laterite based soil mixture for treatment of
      landfill leachate.
AB  - Landfill leachate poses environmental threats worldwide and causes severe issues
      on adjacent water bodies and soil by direct discharge. The primary objective of
      this study is to analyze the efficient use of compost and laterite mixtures (0,
      10, 20, 30 and 40 wt% compost/laterite) on leachate treatment and to investigate
      the associated removal efficiencies under different sorption processes.
      Therefore, in the experimental design, laterite is used for providing adsorption
      characteristics, and compost for activating biological properties of the filter.
      The filtering process is continued until major physical changes occur in the
      filter at approximately 100 days. The raw leachate used for the experiment shows
      higher average values for many analyzed parameters. Parameters for the experiment
      are selected based on their availability in raw leachate in the Sri Lanka. During
      filtering, removal efficiencies of BOD (>90%), COD (>85%), phosphate (>90%) and
      nitrate (75-95%) show higher values for all filters. These removals are mainly
      associated with biodegradation, which is activated by the added compost. Perhaps
      the removal of nitrate steadily increases with time, which indicates in
      denitrification by the added excess carbon from the leachate. The removal of
      total suspended solids (TSS) is moderate to high, but conversely, the electric
      conductivity (EC) is unsteady, indicating an association between iron exchange
      and carbonate degradation. A very high removal efficiency is reported in Fe (90
      100%), and wide ranges of efficiencies in Mn (30-90%), Cu (45-85%), Ni (30-93%),
      Cd (37-98%), Zn (15-98%), and Pb (35-98%) involve heterogeneous sorption
      processes. Furthermore, the normalization of raw leachate by the liquid filtrate
      has apparent improvements. The differences (p > .05) in removal efficiencies
      between the filters are significant. It can be concluded that the filter with
      laterite mixed with 20% of compost has the optimum conditions. Further, the
      Fourier-transforminfrared (FT-IR) models for filter media conclude multiple
      sorptions and reveal evidence on vacant sites. X-ray diffraction (XRD) analyses
      indicate secondary minerals gibbsite, hematite, goethite and kaolinite as the
      major minerals that involved on the sorption process.

PMID- 29336954
TI  - High voltage fragmentation of composites from secondary raw materials - Potential
      and limitations.
AB  - The comminution of composites for liberation of valuable components is a costly
      and energy-intensive process within the recycling of spent products. It therefore
      is continuously studied and optimized. In addition to conventional mechanical
      comminution innovative new principles for size reduction have been developed. One
      is the use of high voltage (HV) pulses, which is known to be a technology
      selectively liberating along phase boundaries. This technology offers the
      advantage of targeted liberation, preventing overgrinding of the material and
      thus improving the overall processing as well as product quality. In this study,
      the high voltage fragmentation of three different non-brittle composites
      (galvanized plastics, carbon fibre composites, electrode foils from Li-ion
      batteries) was investigated. The influence of pulse rate, number of pulses and
      filling level on the liberation and efficiency of comminution is discussed. Using
      the guideline VDI 2225 HV, fragmentation is compared to conventional mechanical
      comminution with respect to numerous criteria such as cost, throughput, energy
      consumption, availability and scalability. It was found that at current state of
      development, HV fragmentation cannot compete with mechanical comminution beyond
      laboratory scale.

PMID- 29336955
TI  - Assessing Gaps in the HIV Care Continuum in Young Men Who Have Sex With Men: The
      P18 Cohort Study.

PMID- 29336957
TI  - Human-Snake Encounters and Folk Remedies in Nepal.

PMID- 29336956
TI  - Reverse transcription loop-mediated isothermal amplification for species-specific
      detection of tomato chlorotic spot orthotospovirus.
AB  - Tomato chlorotic spot orthotospovirus (TCSV) is an emerging orthotospovirus that
      can cause severe disease on tomato plants. There are at least four
      orthotospoviruses infecting tomato, and mixed infection of two or more
      orthotospoviruses in a single tomato plant is quite common in the field. With
      similarity in the symptomatology and cross serological reactivity among tomato
      infecting orthotospoviruses, especially between TCSV and groundnut ringspot
      orthotospovirus (GRSV), the current serological tests could not achieve definite
      and accurate species-specific determination in disease diagnosis. Here, a one
      step reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay
      was developed for TCSV. Under optimum conditions, the virus was detected in as
      little as 0.2 ng of total RNA or in 1:10,000 dilution of a simple diluted tissue
      extract, which was ten times more sensitive than a conventional RT-PCR assay. The
      RT-LAMP assay was highly specific for TCSV, with no cross reaction with the other
      two orthotospoviruses: GRSV and tomato spotted wilt orthotospovirus (TSWV). These
      results demonstrate that this simple and sensitive RT-LAMP could be used to
      achieve species-specific detection for TCSV under field conditions.

PMID- 29336958
TI  - Prehospital Emergencies in Illegal Gold Mining Sites in French Guiana.
AB  - INTRODUCTION: Illegal gold mining is flourishing in French Guiana, existing
      outside the law due to both the high cost of gold mining permits and the
      challenges of law enforcement within the Amazon forest. We report the
      characteristics of, and the medical responses to, medical emergencies in illegal
      gold mining sites. METHODS: We performed a retrospective study of all medical
      emergencies reported from illegal gold mining sites to the centralized call
      office of SAMU 973 from 1998 through 2000 and from 2008 through 2010. According
      to the national health care system, any medical emergency within the territory is
      handled by the prehospital emergency medical service (SAMU 973), irrespective of
      the patients' legal status. Data were extracted from the SAMU 973 notebook
      registry (1998-2000) or the SAMU 973 computerized database (2008-2010) and werre
      collected using a standardized questionnaire. RESULTS: Of 71,932 calls for
      medical emergencies in French Guiana during the study periods, 340 (0.5%)
      originated from illegal gold mining sites. Of these, 196 (58%) led to medical
      evacuation by helicopter, whereas the overall rate of evacuation by helicopter
      after placing a call to SAMU 973 was only 4% (3020/71,932; P<0.0001 for
      comparison with illegal gold mining sites). Medical emergencies were classified
      as illness (48%, mostly infectious), trauma (44%, mostly weapon wounds), and
      miscellaneous (8%). CONCLUSIONS: Medical emergencies at illegal gold mining sites
      in the Amazon forest mostly include infectious diseases, followed by trauma, and
      often require medical evacuation by helicopter. Our study suggests that
      implementation of preventive medicine within gold mining sites, irrespective of
      their legal status, could be cost-effective and reduce morbidity.

PMID- 29336959
TI  - Psychological Attributes of Ultramarathoners.
AB  - INTRODUCTION: As the popularity of ultramarathon participation increases, there
      still exists a lack of understanding of the unique psychological characteristics
      of ultramarathon runners. The current study sought to investigate some of the
      psychological and behavioral factors that are involved in ultramarathon running.
      METHODS: We obtained information from participants of the Bear Chase Trail Race
      via an online survey. This race is a single-day, multidistance race consisting of
      a 10 k, half marathon, 50 k, 50 mi, and 100 k run in Lakewood, Colorado, at a
      base altitude of 1680 m with total altitude in climbs ranging from 663 to 2591 m.
      We correlated information from the Exercise Addiction Inventory and the Patient
      Health Questionnaire-2 and demographic information with race finish times.
      RESULTS: Out of 200 runners who started the race, 98 (48%) completed the survey.
      Over half of the runners were men (61.2%), and the average age was 39.0 years
      (SD+/-8.9; range 21-64 years). A number of respondents (20%) screened positive
      for exercise addiction concerns. Approximately 20% of our sample screened
      positive for depressive symptoms (Patient Health Questionnaire-2 score >3). The
      majority of participants reported receiving strong social support from current
      partners with regard to their ultramarathon running training time and goals.
      CONCLUSIONS: Although only a screening, the number of positive screens on the
      Exercise Addiction Inventory suggests use of screening measures with an
      ultramarathon running population. Athletes with positive screening tests should
      be fully evaluated for depression and exercise addiction because this would
      enable appropriate athlete support and treatment referral.

PMID- 29336960
TI  - PRO: Prothrombin Complex Concentrate Should Be Used in Preference to Fresh Frozen
      Plasma for Hemostasis in Cardiac Surgical Patients.

PMID- 29336961
TI  - Chronic Lung Disease and Mortality after Cardiac Surgery: A Prospective Cohort
      Study.
AB  - OBJECTIVE: To investigate the 1-year survival in cardiac surgical patients with
      lung disease, including previously undiagnosed cases. DESIGN: Prospective cohort
      study. SETTING: Tertiary hospital. PARTICIPANTS: Patients scheduled for elective
      coronary artery bypass graft (CABG) surgery. INTERVENTIONS: None. MEASUREMENTS
      AND MAIN RESULTS: Pulmonary function tests (PFTs) were performed in 454 patients
      before surgery. Abnormal respiratory patterns were defined as follows:
      obstructive (forced expiratory volume in 1 second/forced vital capacity <0.70),
      restrictive (forced expiratory volume in 1 second/forced vital capacity >=0.70
      and forced vital capacity <80% of predicted), and mixed. Overall 1-year mortality
      was 3.3%. Among 31 patients with documented chronic obstructive pulmonary disease
      (COPD), mortality was 9.6%, hazard ratio (HR) 1.28, 95% confidence interval (CI)
      1.02-12.80, p = 0.04. Of 423 patients without history of COPD, 57 obstructive, 46
      restrictive, and 4 mixed abnormal patterns were identified. Of a total of 72 with
      obstructive lung disease confirmed by PFT (ie, 15 of COPD patients and 57 newly
      identified cases), 6.9% died, HR 2.75, 95% CI 0.98-8.07, p = 0.06. When combined
      with cases of COPD where a respiratory abnormality was confirmed (26 patients),
      newly diagnosed obstructive lung disease (57 patients) was significantly
      associated with 1-year mortality, HR 4.13, 95% CI 1.50-11.42, p = 0.006. The
      adjustment for EuroSCORE II did not change the results. CONCLUSIONS: Combination
      of confirmed preexisting lung disease and newly diagnosed cases provides a clear
      link to mid-term mortality.

PMID- 29336962
TI  - Preoperative Left Ventricular Diastolic Dysfunction and One-Year Survival in
      Patients Undergoing Transcatheter Aortic Valve Replacement.

PMID- 29336963
TI  - Ultrasound Guided Cannulation of the Carotid Artery in Extensive Aortic
      Dissection Involving the Aortic Arch Branch Vessels.

PMID- 29336964
TI  - Continuous Erector Spinae Plane (ESP) Block for Postoperative Analgesia after
      Minimally Invasive Mitral Valve Surgery.

PMID- 29336965
TI  - Tracheostomy Insertion During Venovenous Extracorporeal Membrane Oxygenation: Do
      the Benefits Outweigh the Risks?

PMID- 29336966
TI  - Conversion from Monitored Anesthesia Care to General Anesthesia for Transcatheter
      Aortic Valve Replacement.

PMID- 29336967
TI  - Con: Activated Clotting Time Should Not Be Monitored During Heparinization for
      Vascular Surgery.

PMID- 29336968
TI  - Reappearance of Motor-Evoked Potentials During the Rewarming Phase After Deep
      Hypothermic Circulatory Arrest.
AB  - OBJECTIVE: Although motor-evoked potentials (MEPs) disappear in deep hypothermic
      circulatory arrest (DHCA), MEPs have been used to confirm whether motor function
      is intact after DHCA. It is crucial to know the timing, body temperature, and MEP
      amplitude at MEP reappearance to detect spinal cord ischemia after DHCA. However,
      data on these parameters are sparse. The authors investigated the characteristics
      of MEPs at reappearance after DHCA. DESIGN: A retrospective observational study.
      SETTING: Single national center. PARTICIPANTS: Sixty-one patients who underwent
      descending aortic replacement and thoracoabdominal aortic replacement with DHCA
      between January 2013 and December 2015. INTERVENTIONS: None. MEASUREMENTS AND
      MAIN RESULTS: The authors extracted the following data: time to MEP reappearance
      after the end of lower extremity circulatory arrest, bladder temperature (BT) and
      nasopharyngeal temperature (NPT) when MEPs recovered, and %amplitude of MEPs
      relative to control values at MEP reappearance. The median time to MEP
      reappearance was approximately 70 minutes. BT at MEP reappearance ranged from
      34.3 degrees C to 34.6 degrees C and NPT ranged from 36.2 degrees C to 36.4
      degrees C. At MEP reappearance, %amplitude less than 50% of the control value was
      observed in more than 50% of patients. Time to MEP reappearance had a significant
      positive association with rewarming time (p < 0.01) and BT (p = 0.03).
      CONCLUSIONS: There was a wide variation in MEP amplitude at reappearance during
      the rewarming phase. BT was approximately 34 degrees C when MEPs in the leg
      recovered. The time to MEP reappearance is influenced significantly by rewarming
      time and BT.

PMID- 29336969
TI  - Delayed Seroconversion in a Patient With Heparin-Induced Thrombocytopenia.

PMID- 29336970
TI  - A Nasal Ventilation Mask for a Morbidly Obese Patient with OSA and Atrial
      Fibrillation undergoing Cardioversion.

PMID- 29336971
TI  - Inhaled Nitric Oxide (iNO) and Inhaled Epoprostenol (iPGI2) Use in Cardiothoracic
      Surgical Patients: Is there Sufficient Evidence for Evidence-Based
      Recommendations?

PMID- 29336972
TI  - General Anesthesia for Transcatheter Aortic Valve Replacement: Total Intravenous
      Anesthesia is Associated with Less Delirium as Compared to Volatile Agent
      Technique.
AB  - OBJECTIVE: Investigate the effect of volatile anesthesia versus total intravenous
      anesthesia on the incidence of postoperative delirium and length of stay in
      patients undergoing transcatheter aortic valve replacement under general
      anesthesia. DESIGN: Retrospective study. SETTING: Single institution, academic
      medical center. PARTICIPANTS: Adult patients who underwent transcatheter aortic
      valve replacement under general anesthesia between November 2014 and February
      2017. INTERVENTIONS: This study was not an interventional study. MEASUREMENTS AND
      MAIN RESULTS: Electronic medical records were reviewed for intraoperative
      maintenance anesthetic technique, hospital and intensive care unit length of
      stay, 30-day mortality, and documentation of delirium. Delirium was defined as
      either 1) positive Confusion Assessment Method for the Intensive Care Unit score
      or 2) documentation of delirium or confusion by the care team within 2 days of
      surgery. Overall, 116 patients were included and 84 (72%) received a total
      intravenous anesthesia technique. Twenty-three patients (20%) had postoperative
      delirium. The odds of delirium were lower in patients undergoing transcatheter
      aortic valve replacement with total intravenous anesthesia, compared with
      volatile anesthesia, even after adjusting for procedure approach (odds ratio
      0.22, 95% confidence interval 0.06, 0.79, p = 0.02). No significant difference in
      hospital or intensive care unit length of stay was seen after adjusting for
      procedural characteristics. CONCLUSIONS: While postoperative delirium is a
      complex and multifactorial problem, the type of general anesthetic maintenance
      may contribute to the incidence of postoperative delirium in patients undergoing
      transcatheter aortic valve replacement, and total intravenous anesthesia may be
      an attractive alternative to volatile-based general anesthesia maintenance.

PMID- 29336973
TI  - Redo Mitral Surgery: Risk, Outcomes, and the Scope of Transcatheter
      Interventions.

PMID- 29336974
TI  - Commentary on "Superior Reproducibility of the Leading to Leading Edge and Inner
      to Inner Edge Methods in the Ultrasound Assessment of Maximum Abdominal Aortic
      Diameter".

PMID- 29336975
TI  - Mechanical and Biochemical Role of Fibrin Within a Venous Thrombus.
AB  - BACKGROUND: The physical properties of a venous thrombus are derived from
      molecular characteristics, including fibrin polymer diameter, density, branching,
      and cross-linking. Dense thrombi with thin, highly branched fibrin fibres and
      small pores in the meshwork have been observed to be more rigid, less permeable,
      and more resistant to lysis. The three dimensional fibrin meshwork acts as the
      main structure to entrap and capture erythrocytes, platelets and plasma
      components. Attached factors become integrated into the developing thrombus, co
      localise with fibrin deposition and act in either a pro- or anticoagulant
      capacity. Similarly, factors including blood flow, osmolarity and pH, oxidative
      stress, platelet and leukocyte recruitment, and thrombin concentration alter
      thrombus composition, architecture, and its mechanical properties. CONCLUSIONS:
      Over time, an increase in thrombus cellular composition and a linear decrease in
      fibrin content as a function of thrombus age is observed. However, little else is
      known regarding the evolution of fibrin based clots. The role of fibrin in
      mediating cellular coordination, thrombus maturation, and changes of the venous
      wall also requires further research. This review discusses the current impact of
      fibrin on thrombus remodeling and addresses the limitations of the work done in
      this area.

PMID- 29336976
TI  - Venus Flytrap: How an Excitable, Carnivorous Plant Works.
AB  - The carnivorous plant Dionaea possesses very sensitive mechanoreceptors. Upon
      contact with prey an action potential is triggered which, via an electrical
      network - comparable to the nervous system of vertebrates - rapidly closes its
      bivalved trap. The 'hunting cycle' comprises a constitutively activated mechanism
      for the rapid capture of prey, followed by a well-orchestrated sequence of
      activation of genes responsible for tight trap closure, digestion of the prey,
      and uptake of nutrients. Decisions on the step-by-step activation are based on
      'counting' the number of stimulations of sensory organs. These remarkable animal
      like skills in the carnivore are achieved not by taking over genes from its prey
      but by modifying and rearranging the functions of genes that are ubiquitous in
      plants.

PMID- 29336977
TI  - The role of extended venous thromboembolism prophylaxis following urologic pelvic
      surgery.
AB  - With the emergence of evidence that venous thromboembolisms (VTE) typically
      occurs following discharge after urologic pelvic surgery, the focus on extended
      VTE prophylaxis has intensified. Urologists should have a comprehensive
      understanding of various VTE risk factors in order to weigh the risk of
      postoperative hemorrhage with the possibility of fatal pulmonary embolus. Risk
      factors such as advanced age, obesity, and active malignancy are especially
      common in patient's undergoing urologic pelvic surgery, and thus this issue
      becomes particularly relevant to the practicing urologist. In previous years,
      guidelines on extended VTE prophylaxis have either been vague or not urology
      specific; however, the European Association of Urology has recently issued
      recommendations on VTE prophylaxis stratified by VTE risk and surgery type.
      Although these guidelines are a major advance, definitive answers on this
      question may prove elusive in the form of prospective randomized data given the
      low incidence of clinically significant postoperative VTE.

PMID- 29336978
TI  - Metastatic burden in newly diagnosed hormone-naive metastatic prostate cancer:
      Comparing definitions of CHAARTED and LATITUDE trial.
AB  - OBJECTIVES: No uniformity exists in the definition of metastatic burden in
      metastatic hormone-naive prostate cancer (mHNPC) across clinical trials making
      their comparison challenging. We explored definition agreement and prognostic
      significance of bulky mHNPC according to the CHAARTED and LATITUDE trial.
      MATERIALS AND METHODS: Since 2014, 95 patients with newly diagnosed mHNPC were
      prospectively registered. For this study, they were categorized as having high
      volume (HVD) vs. low-volume (LVD) and high-risk (HRD) vs. low-risk disease (LRD)
      according to the definition of CHAARTED and LATITUDE, respectively. Agreement was
      tested using Cohen's kappa coefficient. The Kaplan-Meier method was used to
      compare castration-resistant prostate cancer-free survival (CRPC-FS) and overall
      survival (OS). Prognostic significance was analyzed using Cox regression models.
      RESULTS: In total, 44 (46%) and 46 (48%) patients showed HVD and HRD,
      respectively. Cohen's kappa coefficient was 0.83 indicating "almost perfect"
      agreement (P<0.001). Median CRPC-FS was 40 (95% CI: 25-55) vs. 11 months (95% CI:
      8-14) for LVD and HVD (P = 0.001); 40 (95% CI: 27-53) vs. 11 months (95% CI: 8
      14) for LRD and HRD (P<0.001), respectively. Median OS was not reached vs. 51
      months (95% CI: 0-102) for LVD and HVD (P = 0.001); not reached vs. 51 months
      (95% CI: 2-100) for LRD and HRD (P = 0.003), respectively. The prognostic
      significance of both definitions remained significant in the multivariate model
      for CRPC-FS (P = 0.012 and P = 0.003). CONCLUSIONS: There is an excellent
      agreement between the definitions of bulky mHNPC in the CHAARTED and LATITUDE
      trial. Both definitions have significant prognostic value for predicting worse
      CRPC-FS and OS.

PMID- 29336979
TI  - Prostate magnetic resonance imaging: The truth lies in the eye of the beholder.
AB  - PURPOSE: To determine the diagnostic accuracy and interobserver variability of
      radiologic interpretation of magnetic resonance imaging (MRI) performed for
      surgical planning before prostatectomy. PATIENTS AND METHODS: The records of 233
      men undergoing prostatectomy with presurgical multiparametric 3T surface body
      coil MRI were reviewed. All initial films were read by a fellowship-trained body
      radiologist provided with relevant clinical information. A senior radiologist
      then reread all pelvic MRIs blinded to the initial interpretation with findings
      from both readings compared to final pathology. Kappa (kappa) scores as well as
      sensitivity, specificity, positive predictive values (PPV), negative predictive
      value (NPV), and accuracy were determined. RESULTS: When considering
      extraprostatic extension (EPE), there was low concordance comparing the initial
      vs. repeat MRI interpretation (kappa = 0.22). Additionally, when the senior
      radiologist reread his own initial interpretation (n = 93, blinded to initial
      result), concordance for EPE was greater (kappa = 0.36) albeit similarly low.
      With regard to EPE, a comparison of initial MRI interpretation vs. reread by
      senior radiologist noted universal improvements in diagnostic characteristics
      including sensitivity (30.3% vs. 56.1%), specificity (80.2% vs. 88.6%), PPV
      (37.7% vs. 66.1%), NPV (74.4% vs. 83.6%), and accuracy (66.1% vs. 79.4%). In
      contrast, seminal vesicle invasion interpretation was more uniform whereby
      initial MRI interpretation vs. reread yielded similar sensitivity (18.2% vs.
      27.3%), specificity (97.2% vs. 93.8%), PPV (40.0% vs. 31.6%), NPV (91.9% vs.
      92.5%), and accuracy (89.7% vs. 87.6%). CONCLUSIONS: Even at a tertiary referral
      center, interobserver variability among radiologists regarding local extent of
      disease on prostate MRI is high. These observations underscore the importance of
      uniformity when defining criteria for EPE and seminal vesicle invasion to allow
      for optimal presurgical planning.

PMID- 29336980
TI  - Surfactant Effects on Lipid-Based Vesicles Properties.
AB  - Understanding the effect of surfactant properties is critical when designing
      vesicular delivery systems. This review evaluates previous studies to explain the
      influence of surfactant properties on the behavior of lipid vesicular systems,
      specifically their size, charge, stability, entrapment efficiency,
      pharmacokinetics, and pharmacodynamics. Generally, the size of vesicles decreases
      by increasing the surfactant concentration, carbon chain length, the
      hydrophilicity of the surfactant head group, and the hydrophilic-lipophilic
      balance. Increasing surfactant concentration can also lead to an increase in
      charge, which in turn reduces vesicle aggregation and enhances the stability of
      the system. The vesicles' entrapment efficiency not only depends on the
      surfactant properties but also on the encapsulated drug. For example, the
      encapsulation of a lipophilic drug could be enhanced by using a surfactant with a
      low hydrophilic-lipophilic balance value. Moreover, the membrane permeability of
      vesicles depends on the surfactant's carbon chain length and transition
      temperature. In addition, surfactants have a clear influence on pharmacokinetics
      and pharmacodynamics such as sustaining drug release, enhancing the circulation
      time of vesicles, improving targeting and cellular uptake.

PMID- 29336982
TI  - IL-6 receptor blockade ameliorates diabetic nephropathy via inhibiting
      inflammasome in mice.
AB  - BACKGROUND AND OBJECTIVE: Interleukin 6 (IL-6) has been identified as a key
      mediator in inflammation, immune responses and glucose metabolism. In this study,
      we assessed the effects of an IL-6 receptor antibody on diabetic nephropathy in a
      mouse model of type 2 diabetes mellitus. METHODS: Twelve week old male db/db mice
      were treated with Tocilizumab (an IL-6 receptor antibody), normal IgG1 control
      antibody, insulin or normal saline for 12 weeks. Renal injury, inflammation and
      insulin resistance were assessed. RESULTS: Db/db mice treated with Tocilizumab
      exhibited reduced proteinuria and glomerular mesangial matrix accumulation
      compared to db/db + IgG controls. Additionally, Tocilizumab suppressed
      inflammatory response, oxidative stress and the IL-6 signaling pathway in the
      diabetic kidneys. It is noteworthy that blockade of IL-6 receptor blunted the
      activation of NLRP3 inflammasome partly through inhibition of IL-17A.
      Furthermore, insulin resistance assessed by glucose tolerance test, was
      ameliorated by Tocilizumab treatment. CONCLUSIONS: The protective effects of an
      IL-6 receptor blockade against diabetic renal injury may be due to decreased
      insulin resistance and inhibition of the inflammasome.

PMID- 29336981
TI  - Challenges and Opportunities for the Subcutaneous Delivery of Therapeutic
      Proteins.
AB  - Biotherapeutics is a rapidly growing drug class, and over 200 biotherapeutics
      have already obtained approval, with about 50 of these being approved in 2015 and
      2016 alone. Several hundred protein therapeutic products are still in the
      pipeline, including interesting new approaches to treatment. Owing to patients'
      convenience of at home administration and reduced number of hospital visits as
      well as the reduction in treatment costs, subcutaneous (SC) administration of
      biologics is of increasing interest. Although several avenues for treatment using
      biotherapeutics are being explored, there is still a sufficient gap in knowledge
      regarding the interplay of formulation conditions, immunogenicity, and
      pharmacokinetics (PK) of the absorption of these compounds when they are given
      SC. This review seeks to highlight the major concerns and important factors
      governing this route of administration and suggest a holistic approach for
      effective SC delivery.

PMID- 29336983
TI  - A response to S. Basu (2017).

PMID- 29336984
TI  - Can the problem of the observability of other minds be solved in the lab?:
      Comment on "Seeing mental states: An experimental strategy for measuring the
      observability of other minds" by Cristina Becchio et al.

PMID- 29336986
TI  - A systematic literature review of observational studies of the bidirectional
      association between metabolic syndrome and migraine.
AB  - AIMS: To evaluate all epidemiological evidence in the literature linking the
      metabolic syndrome (MetS) and migraine in adults. METHODS: Database (Medline,
      Embase; published reports up to November 2017) and manual searches were
      performed. Information on data collection, sample characteristics, study design,
      MetS and migraine assessment, and results was extracted from each relevant
      publication. The methodological quality of each study was also assessed. RESULTS:
      A total of 15 observational epidemiological studies in adults, published between
      2009 and 2017, were retrieved. Of these, one employed a prospective design, while
      the rest had a cross-sectional (13 studies) or case-control (one study) design.
      Five studies assessed the presence of migraine in individuals with MetS, whereas
      10 studies assessed the presence or risk of MetS in migraineurs. Most
      participants were female hospital outpatients. The sole prospective cohort study
      reported 11-year MetS incidence of 21.8% in migraineurs with aura, 16.8% in
      migraineurs without aura and 14.5% in subjects without headaches. Most studies
      (60%) provided no statistical estimates of association. Methodological flaws
      included selection biases, lack of power analysis, unsuitable research plans and
      no multivariable analyses. Meta-analysis was not feasible with the available
      data. CONCLUSION: Our systematic review has identified major gaps in knowledge
      and weaknesses in research that should provide an impetus for future
      epidemiological investigations using more rigorous methodology, large general
      population prospective cohorts, and substantial data on dietary behaviours and
      lifestyle.

PMID- 29336985
TI  - The Blacklegged Tick, Ixodes scapularis: An Increasing Public Health Concern.
AB  - In the United States, the blacklegged tick, Ixodes scapularis, is a vector of
      seven human pathogens, including those causing Lyme disease, anaplasmosis,
      babesiosis, Borrelia miyamotoi disease, Powassan virus disease, and ehrlichiosis
      associated with Ehrlichia muris eauclarensis. In addition to an accelerated rate
      of discovery of I. scapularis-borne pathogens over the past two decades, the
      geographic range of the tick, and incidence and range of I. scapularis-borne
      disease cases, have increased. Despite knowledge of when and where humans are
      most at risk of exposure to infected ticks, control of I. scapularis-borne
      diseases remains a challenge. Human vaccines are not available, and we lack solid
      evidence for other prevention and control methods to reduce human disease. The
      way forward is discussed.

PMID- 29336988
TI  - Superior Mesenteric Artery Syndrome: An Uncommon Cause of Abdominal Pain.

PMID- 29336987
TI  - The in vitro radiosensitizer potential of resveratrol on MCF-7 breast cancer
      cells.
AB  - Radiation therapy is commonly applied in breast cancer (BC) patients. However,
      radioresistance and side effects are limiting factors of this practice.
      Therefore, studying substances that can enhance the radiation effect and, at the
      same time, protect normal cells is very relevant. Thus, the aim of this work was
      to assess the radiosensitizer effect of resveratrol (RV) on BC cells (MCF-7). A
      high cytotoxic and antiproliferative effect was observed in the treatment with 10
      MUM of RV + 3 Gy ionizing radiation (IR). Our results indicate that, 24 h after
      the exposition of cell cultures to RV + IR, an induction of necrosis/senescence
      has occurred. Furthermore, was observed the activation of extrinsic apoptosis
      pathway through a decrease of the Bax/Bcl-2 ratio and a high activity of caspase
      8. Moreover, our data show that this treatment affected the oxidative cell
      metabolism, increasing oxidative protein, lipid and membrane damage and also
      acted to decrease the antioxidant enzymes activity. The antiproliferative effect
      on 72 h cultures may be associated with a high expression of p53 and an
      interruption of cell cycle in the S phase. Therefore, our results suggest that RV
      is a potential radiosensitizer of MCF-7 BC cells.

PMID- 29336989
TI  - Are Geriatric Patients Placed in an Emergency Department Observation Unit on a
      Chest Pain Pathway More Likely Than Non-Geriatric Patients to Re-Present to the
      Hospital within 30 Days?
AB  - BACKGROUND: Emergency department observation units (EDOUs) are used frequently
      for low-risk chest pain evaluations. OBJECTIVE: The purpose of this study was to
      determine whether geriatric compared to non-geriatric patients evaluated in an
      EDOU for chest pain have differences in unscheduled 30-day re-presentation,
      length of stay (LOS), and use of stress testing. METHODS: We conducted an
      exploratory, retrospective, cohort study at a single academic, urban ED of all
      adult patients placed in an EDOU chest pain protocol from June 1, 2014 to May 31,
      2015. Our primary outcome was any unscheduled return visits within 30 days of
      discharge from the EDOU. Secondary outcomes included EDOU LOS and stress testing.
      We used Wilcoxon non-parametric and chi2 tests to compare geriatric to non
      geriatric patients. RESULTS: There were 959 unique EDOU placements of geriatric
      (n = 219) and non-geriatric (n = 740) patients. Geriatric compared to non
      geriatric patients had: no significant difference in unscheduled 30-day return
      visits after discharge from the EDOU (15.5% vs. 18.5%; p = 0.31); significantly
      longer median EDOU LOS (22.1 vs. 20.6 h; p < 0.01) with a greater percentage
      staying longer than 24 h (42% vs. 29.1%; p < 0.01). Geriatric patients had
      significantly fewer stress tests (39.7% vs. 51.4%; p < 0.01), more of which were
      nuclear stress tests (78.2% vs. 39.5%; p < 0.01). CONCLUSIONS: In this
      exploratory retrospective study, geriatric EDOU chest pain patients did not have
      an increased rate of re-presentation to the hospital within 30 days compared to
      non-geriatric patients. Geriatric patients had a longer EDOU LOS than non
      geriatric patients. Geriatric patients in the EDOU had fewer stress tests, but
      more of those were nuclear stress tests.

PMID- 29336990
TI  - Failure of Intracardiac Pacing After Fatal Propafenone Overdose: A Case Report.
AB  - BACKGROUND: Propafenone is a sodium-channel blocker, class IC antiarrhythmic
      drug, frequently used to manage supraventricular dysrhythmias, especially atrial
      fibrillation. We report a self mono-intoxication with propafenone. CASE REPORT: A
      68-year-old woman presented with a decreased level of consciousness, hypotension,
      and electrocardiogram showing QRS widening with atrial asystole and extreme
      bradycardia < 20 beats/min. After initial stabilization with transcutaneous
      pacing, laboratory findings detected normal electrolyte ranges and metabolic
      acidosis, and her medical history revealed availability of propafenone due to
      paroxysmal atrial fibrillation and depressive syndrome, which led to the
      suspicion of intoxication. Despite intravenous sodium bicarbonate, calcium,
      norepinephrine, and aggressive fluid replacement (10% glucose with insulin),
      hemodynamic stability was not achieved. Temporary intracardiac pacing was
      implanted. However, even with multiple electrode positions, effective capture
      could not be achieved. At that time, transcutaneous pacing was also ineffective.
      Consequently, the patient died in refractory asystole due to complete myocardial
      nonexcitability. The concentration of 5270 ng/mL of propafenone was found in the
      blood at autopsy, using gas spectrometry-mass chromatography. It is the third
      highest reported propafenone lethal concentration and the first case in which the
      myocardial nonexcitability refractory to intracardiac pacing was seen despite
      normal electrode position in the right ventricle, with failure to achieve the
      patient's hemodynamic stability. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF
      THIS?: Emergency physicians should be aware of possible propafenone ingestion
      causing toxicity, which is probably more frequent than previously described,
      especially because propafenone is widely available due to its use in managing
      atrial fibrillation, the most common arrhythmia nowadays.

PMID- 29336991
TI  - SIRPalpha-CD47 Immune Checkpoint Blockade in Anticancer Therapy.
AB  - Inhibitory immune checkpoint blockade has been one of the most significant
      advances in anticancer therapy of the past decade. Research so far has largely
      focused on improving adaptive immune functions, but recent studies have indicated
      that the signal-regulatory protein (SIRP)alpha-CD47 pathway, a phagocytosis
      checkpoint in macrophages and other innate immune cells, may be an interesting
      therapeutic target. Here, we summarize current knowledge about SIRPalpha-CD47
      blockade, and highlight key issues for future investigations. These include the
      targeting of prophagocytic receptors (Fc receptors or otherwise) to complement
      SIRPalpha-CD47 blockade, the understanding of constraints on phagocytosis other
      than the SIRPalpha-CD47 checkpoint and the contribution of immune cells other
      than macrophages. A better understanding of how SIRPalpha-CD47 blockade works may
      aid in identifying patients suitable for this therapy, avoiding potential
      toxicities and designing optimal combination therapies.

PMID- 29336992
TI  - Schwann cell lamellipodia regulate cell-cell interactions and phagocytosis.
AB  - Lamellipodia in Schwann cells (SCs) are crucial for myelination, but their other
      biological functions remain largely uncharacterised. Two types of lamellipodia
      exist in SCs: axial lamellipodia at the outermost edge of the cell processes, and
      radial lamellipodia appearing peripherally along the entire cell. We have
      previously shown that radial lamellipodia on olfactory glia (olfactory
      ensheathing cells; OECs) promote cell-cell adhesion, contact-mediated migration
      and phagocytosis. Here we have investigated whether lamellipodia in SCs have
      similar roles. Using live-cell imaging, we show that the radial lamellipodia in
      SCs are highly motile, appear at multiple cellular sites and rapidly move in a
      wave-like manner. We found that axial and radial lamellipodia had strikingly
      different roles and are regulated by different intracellular pathways. Axial
      lamellipodia initiated interactions with other SCs and with neurons by contacting
      radial lamellipodia on SCs, and budding neurites/axons. Most SC-SC interactions
      resulted in repulsion, and, lamellipodial activity (unlike in OECs) did not
      promote contact-mediated migration. We show that lamellipodia are crucial for SC
      mediated phagocytosis of both axonal debris and bacteria, and demonstrated that
      inhibition of lamellipodial activity by blocking the Rho/Rac pathways also
      inhibits phagocytosis. We also show that heregulin, which induces SC
      differentiation and maturation, alters lamellipodial behaviour but does not
      affect phagocytic activity. Overall, the results show that SC lamellipodia are
      important for cell interactions and phagocytosis.

PMID- 29336993
TI  - WORLDSymposiumTM 2018 Introduction.

PMID- 29336994
TI  - Agreement between the results of meta-analyses from case reports and from
      clinical studies regarding the efficacy of laronidase therapy in patients with
      mucopolysaccharidosis type I who initiated enzyme replacement therapy in adult
      age: An example of case reports meta-analyses as an useful tool for evidence
      based medicine in rare diseases.
AB  - BACKGROUND: Case reports might have a prominent role in the rare diseases field,
      due to the small number of patients affected by one such disease. A previous
      systematic review regarding the efficacy of laronidase therapy in patients with
      mucopolysaccharidosis type I (MPS-I) who initiated enzyme replacement therapy
      (ERT) in adult age has been published. The review included a meta-analysis of 19
      clinical studies and the description of eleven case reports. It was of interest
      to perform a meta-analysis of those case reports to explore the role of such meta
      analyses as a tool for evidence-based medicine in rare diseases. METHODS: The
      study included all case reports with standard treatment regimen. Primary analysis
      was the percentage of case reports showing an improvement in a specific outcome.
      Only when that percentage was statistically higher than 5%, the improvement was
      confirmed as such. The outcomes that accomplished this criterion were ranked and
      compared to the GRADE criteria obtained by those same outcomes in the previous
      meta-analysis of clinical studies. RESULTS: There were three outcomes that had a
      significant improvement: Urine glycosaminoglycans, liver volume and 6-minute
      walking test. Positive and negative predictive values, sensitivity and
      specificity for the results of the meta-analysis of case reports as compared to
      that of clinical studies were 100%, 88.9%, 75% and 100%, respectively.
      Accordingly, absolute (Rho=0.82, 95%CI: 0.47 to 0.95) and relative agreement
      (Kappa=0.79, 95%CI: 0.593 to 0.99) between the number of case reports with
      improvement in a specific outcome and the GRADE evidence score for that outcome
      were good. Sensitivity analysis showed that agreement between the meta-analysis
      of case reports and that of the clinical studies were good only when using a
      strong confirmatory strategy for outcome improvement in case reports.
      CONCLUSIONS: We found an agreement between the results of meta-analyses from case
      reports and from clinical studies in the efficacy of laronidase therapy in
      patients with MPS-I who initiated ERT in adult age. This agreement suggests that
      combining case reports quantitatively, rather than analyzing them separately or
      qualitatively, may improve conclusions in the field of rare diseases.

PMID- 29336995
TI  - A search for molecular mechanisms underlying male idiopathic infertility.
AB  - Infertility affects approximately 15% of the couples wanting to conceive. In 30 -
      40% of the cases the aetiology of male infertility remains unknown and is called
      idiopathic male infertility. When assisted reproductive technologies are used to
      obtain pregnancy, an adequate (epi)genetic diagnosis of male infertility is of
      major importance to evaluate if a genetic abnormality will be transmitted to the
      offspring. In addition, there is need for better diagnostic seminal biomarkers to
      assess the success rates of these assisted reproductive technologies. This review
      investigated the possible causes and molecular mechanisms underlying male
      idiopathic infertility by extensive literature searches of: (i) causal gene
      mutations; (ii) proteome studies of spermatozoa from idiopathic infertile
      men;(iii) the role of epigenetics; (iv) post-translational modifications; and (v)
      sperm DNA fragmentation in infertile men. In conclusion, male infertility is a
      complex, multi-factorial disorder and the underlying causes often remain unknown.
      Further research on the (epi)genetic and molecular defects in spermatogenesis and
      sperm function is necessary to improve the diagnosis and to develop more
      personalized treatments of men with idiopathic infertility.

PMID- 29336996
TI  - Follicular flushing in patients with poor ovarian response: a systematic review
      and meta-analysis.
AB  - A systematic literature review and meta-analysis was conducted to evaluate the
      effect of follicular flushing on clinical outcomes (primary outcome: mean number
      of cumulus-oocyte-complexes [COC]) in poor-response IVF patients). The
      bibliographic databases OvidMedline (includes Pubmed), Cochrane Library and Web
      of Science were searched electronically for randomized controlled trials (RCT)
      comparing follicular flushing with no flushing. Three RCT with a total of 210
      patients could be included. The mean number of COC did not increase with flushing
      (weighted mean difference: -0.45 COC, 95% CI -1.14 to 0.25, I2 = 70%; P = 0.21;
      three RCT, n = 210). Mean number of metaphase II oocytes and the proportion of
      randomized patients having at least one COC retrieved were no different between
      groups. No difference was observed between groups for mean number of embryos, the
      proportion of randomized patients achieving embryo transfer, clinical pregnancy
      and live birth rates. Procedure duration was significantly increased with
      flushing (P = 0.0006). A positive effect of flushing on any of the investigated
      outcomes could not be observed in the existing literature in patients with poor
      ovarian response. Flushing is unlikely to significantly increase the number of
      oocytes, and the routine use of follicular flushing should, therefore, be
      scrutinized.

PMID- 29336997
TI  - Modulation of nonessential amino acid biosynthetic pathways in virulent Hessian
      fly larvae (Mayetiola destructor), feeding on susceptible host wheat (Triticum
      aestivum).
AB  - Compatible interactions between wheat (Triticum aestivum), and its dipteran pest
      Hessian fly (Hf, Mayetiola destructor) result in successful establishment of
      larval feeding sites rendering the host plant susceptible. Virulent larvae employ
      an effector-based feeding strategy to reprogram the host physiology resulting in
      formation of a protein- and sugar-rich nutritive tissue beneficial to developing
      larvae. Previous studies documented increased levels of nonessential amino acids
      (NAA; that need not be received through insect diet) in the susceptible wheat in
      response to larval feeding, suggesting importance of plant-derived NAA in larval
      nutrition. Here, we investigated the modulation of genes from NAA biosynthetic
      pathways (NAABP) in virulent Hf larvae. Transcript profiling for 16 NAABP genes,
      annotated from the recently assembled Hf genome, was carried out in the feeding
      first-, and second-instars and compared with that of the first-instar neonate
      (newly hatched, migrating, assumed to be non-feeding) larvae. While Tyr, Gln,
      Glu, and Pro NAABP genes transcript abundance declined in the feeding instars as
      compared to the neonates, those for Ala, and Ser increased in the feeding larval
      instars, despite higher levels of these NAA in the susceptible host plant. Asp,
      Asn, Gly and Cys NAABP genes exhibited variable expression profiles in the
      feeding first- and second-instars. Our results indicate that while Hf larvae
      utilize the plant-derived NAA, de novo synthesis of several NAA may be necessary
      to: (i) provide larvae with the requisite amount for sustaining growth before
      nutritive tissue formation and, (ii) overcome any inadequate amounts in the host
      plant, post-nutritive tissue formation.

PMID- 29336998
TI  - Developing a Predictive Model for Clinical Outcomes of Advanced Non-Small Cell
      Lung Cancer Patients Treated With Nivolumab.
AB  - INTRODUCTION: Despite significant improvement of clinical outcomes of advanced
      non-small-cell lung cancer (NSCLC) patients treated with immunotherapy, our
      knowledge of optimal biomarkers is still limited. PATIENTS AND METHODS: We
      retrospectively evaluated 159 advanced NSCLC patients in our institution treated
      with nivolumab after disease progression during platinum-based chemotherapy. We
      correlated several variables with progression-free survival (PFS) to develop the
      immunotherapy, Sex, Eastern Cooperative Oncology Group performance status,
      Neutrophil-to-lymphocyte ratio (NLR), and Delta NLR (iSEND) model. We categorized
      patients into iSEND good, intermediate, and poor risk groups and evaluated their
      clinical outcomes. Performance of iSEND at 3, 6, 9, and 12 months was evaluated
      according to receiver operating characteristic (ROC) curves and internally
      validated using bootstrapping. The association of iSEND risk groups with clinical
      benefit was evaluated using logistic regression. RESULTS: Median follow-up was
      11.5 months (95% confidence interval [CI], 9.4-13.1). There were 50 deaths and 43
      with disease progression without death. PFS rates at 3, 6, 9, and 12 months were
      78.4%, 63.7%, 55.3%, and 52.2% in iSEND good; 79.4%, 44.3%, 25.9%, and 19.2% in
      iSEND intermediate; and 65%, 25.9%, 22.8%, and 17.8% in iSEND poor. Time
      dependent area under ROC curves of iSEND for PFS at 3, 6, 9, and 12 months were
      0.718, 0.74, 0.746, and 0.774. The iSEND poor group was significantly associated
      with progressive disease at 12 +/- 2 weeks (odds ratio, 9.59; 95% CI, 3.8-26.9; P
      < .0001). CONCLUSION: The iSEND model is an algorithmic model that can
      characterize clinical outcomes of advanced NSCLC patients receiving nivolumab
      into good, intermediate, or poor risk groups and might be useful as a predictive
      model if validated independently.

PMID- 29336999
TI  - Faculty Relative Value Unit Incentives and Resident Education.

PMID- 29337000
TI  - Mechanical Forces Program the Orientation of Cell Division during Airway Tube
      Morphogenesis.
AB  - Oriented cell division plays a key role in controlling organogenesis. The
      mechanisms for regulating division orientation at the whole-organ level are only
      starting to become understood. By combining 3D time-lapse imaging, mouse
      genetics, and mathematical modeling, we find that global orientation of cell
      division is the result of a combination of two types of spindles with distinct
      spindle dynamic behaviors in the developing airway epithelium. Fixed spindles
      follow the classic long-axis rule and establish their division orientation before
      metaphase. In contrast, rotating spindles do not strictly follow the long-axis
      rule and determine their division orientation during metaphase. By using both a
      cell-based mechanical model and stretching-lung-explant experiments, we showed
      that mechanical force can function as a regulatory signal in maintaining the
      stable ratio between fixed spindles and rotating spindles. Our findings
      demonstrate that mechanical forces, cell geometry, and oriented cell division
      function together in a highly coordinated manner to ensure normal airway tube
      morphogenesis.

PMID- 29337001
TI  - Antidepressant Treatment Duration in Pediatric Depressive and Anxiety Disorders:
      How Long is Long Enough?
AB  - Anxiety and depressive disorders are common in the pediatric primary care
      setting, and respond to both psychotherapeutic and psychopharmacologic treatment.
      However, there are limited data regarding the optimal treatment duration. This
      article systematically reviews guidelines and clinical trial data related to
      antidepressant treatment duration in pediatric patients with depressive and
      anxiety disorders. The extant literature suggests 9-12 months of antidepressant
      treatment for youth with major depressive disorder. For generalized, separation
      and social anxiety disorders, 6-9 months of antidepressant treatment may be
      sufficient, though many clinicians extend treatment to 12 months based on
      extrapolation of data from adults with anxiety disorders. Such extended treatment
      periods may decrease the risk of long-term morbidity and recurrence; however, the
      goal of treatment is ultimately remission, rather than duration of antidepressant
      pharmacotherapy. Moreover, while evidence-based guidelines represent a starting
      point, appropriate treatment duration varies and patient-specific response,
      psychological factors, and timing of discontinuation must be considered for
      individual pediatric patients.

PMID- 29337002
TI  - Hypothalamic inflammation and malfunctioning glia in the pathophysiology of
      obesity and diabetes: Translational significance.
AB  - Preclinical studies have suggested that chronic inflammation in the brain might
      be associated with multiple metabolic disorders, including obesity and diabetes.
      In particular, hypothalamic inflammation interferes with the endocrine system and
      modulates nutritional homeostasis, leading to metabolic alterations and
      consequent pathologies. With regard to the mechanisms underlying molecular and
      cellular pathogenesis, neurons, non-neuronal cells, and the crosstalk between
      them have gained particular attention. Specifically, malfunctioning glia have
      recently been implicated as an important component of pathological hypothalamic
      inflammation. Hypothalamic inflammation modulates food intake, energy
      expenditure, insulin secretion, hepatic glucose production, and glucose and fatty
      acid metabolism. Moreover, growing evidence suggests that hypothalamic
      inflammation is intrinsically associated with the pathogenesis of obesity,
      diabetes, and their dysfunctional consequences. However, the translational
      significance of hypothalamic inflammation has not yet been fully explored. In
      this review, we cover recent advances suggesting that hypothalamic inflammation
      and glia play a central role in the ontology of obesity, diabetes, and their
      complications. Finally, we explore the possibilities and challenges of targeting
      hypothalamic inflammation as a potential therapeutic strategy.

PMID- 29337003
TI  - Mouse lung fibroblasts are highly susceptible to necroptosis in a reactive oxygen
      species-dependent manner.
AB  - Mouse embryonic fibroblasts (MEFs) have extensively been used to study
      necroptosis, a recently identified form of programmed cell death. However, very
      little is yet known about the role of necroptosis and its regulation by reactive
      oxygen species (ROS) in cell types naturally exposed to high oxygen levels such
      as mouse lung fibroblasts (MLFs). Here, we discover that MLFs are highly
      susceptible to undergo necroptosis in a ROS-dependent manner upon exposure to a
      prototypic death receptor-mediated necroptotic stimulus, i.e. cotreatment with
      tumor necrosis factor (TNF)alpha, Smac mimetic and the caspase inhibitor zVAD.fmk
      (TSZ). Kinetic analysis revealed that TSZ rapidly induces cell death in MLFs.
      Pharmacological inhibition of receptor-interacting protein kinase (RIPK)1 by
      necrostatin-1 (Nec-1) or RIPK3 by GSK'872 significantly rescues TSZ-stimulated
      cell death. Also, genetic silencing of RIPK3 or mixed lineage kinase domain-like
      pseudokinase (MLKL) significantly protects MLFs from TSZ-mediated cell death.
      Prior to cell death, TSZ significantly increases production of ROS. Importantly,
      addition of radical scavengers such as butylated hydroxyanisole (BHA) or alpha
      Tocopherol (alpha-Toc) significantly suppresses TSZ-induced cell death in
      parallel with a significant reduction of ROS generation. Consistently, BHA
      prevented TSZ-triggered phosphorylation of MLKL similar to the addition of
      GSK'872. Thus, our study demonstrates for the first time that MLFs are prone to
      undergo necroptosis in response to a prototypic necroptotic stimulus and
      identifies ROS as important mediators of TSZ-triggered necroptosis.

PMID- 29337004
TI  - Quantitative sensory testing profiles in children, adolescents and young adults
      (6-20 years) with cerebral palsy: Hints for a neuropathic genesis of pain
      syndromes.
AB  - INTRODUCTION: Many patients with cerebral palsy (CP) suffer chronic pain as one
      of the most limiting factors in their quality of life. In CP patients, pain
      mechanisms are not well understood, and pain therapy remains a challenge.
      Quantitative sensory testing (QST) might provide unique information about the
      functional status of the somatosensory system and therefore better guide pain
      treatment. OBJECTIVES: To understand better the underlying pain mechanisms in
      pediatric CP patients, we aimed to assess clinical and pain parameters, as well
      as QST profiles, which were matched to the patients' cerebral imaging pathology.
      PATIENTS AND METHODS: Thirty CP patients aged 6-20 years old (mean age 12 years)
      without intellectual impairment underwent standardized assessments of QST.
      Cerebral imaging was reassessed. QST results were compared to age- and sex
      matched controls (multiple linear regression; Fisher's exact test; linear
      correlation analysis). RESULTS: CP patients were less sensitive to all mechanical
      and thermal stimuli than healthy controls but more sensitive to all mechanical
      pain stimuli (each p < 0.001). Fifty percent of CP patients showed a combination
      of mechanical hypoesthesia, thermal hypoesthesia and mechanical hyperalgesia; 67%
      of CP patients had periventricular leukomalacia (PVL), which was correlated with
      mechanic (r = 0.661; p < 0.001) and thermal (r = 0.624; p = 0.001) hypoesthesia.
      CONCLUSION: The combination of mechanical hypoesthesia, thermal hypoesthesia and
      mechanical hyperalgesia in our CP patients implicates lemniscal and
      extralemniscal neuron dysfunction in the thalamus region, likely due to PVL. We
      suspect that extralemniscal tracts are involved in the original of pain in our CP
      patients, as in adults.

PMID- 29337005
TI  - Walker-Warburg syndrome and tectocerebellar dysraphia: A novel association caused
      by a homozygous DAG1 mutation.
AB  - OBJECTIVES: To elaborate the imaging phenotype associated with a homozygous
      c.743C > del frameshift mutation in DAG1 leading to complete absence of both
      alpha- and beta-dystroglycan previously reported in a consanguineous Israeli-Arab
      family. METHODS: We analyzed prenatal and postnatal imaging data of patients from
      a consanguineous Israeli-Arab kindred harboring the DAG1 mutation. RESULTS: The
      imaging studies (fetal ultrasound, CT scan and postnatal MRI) demonstrated: flat
      cortex (abnormally thick with irregular pebbled cortical-white matter border on
      MRI), hydrocephalus, scattered small periventricular heterotopia and subependymal
      hemorrhages and calcifications, z-shaped brainstem, and in addition an occipital
      encephalocele, vermian agenesis, and an elongated and thick tectum
      (tectocerebellar dysraphia). CONCLUSIONS: The novel association of cobblestone
      malformation with tectocerebellar dysraphia as part of WWS is characteristic of
      the homozygous c.743C > del frameshift mutation in the DAG1 gene.

PMID- 29337007
TI  - Postnatal post-traumatic stress: An integrative review.
AB  - PROBLEM: Post-traumatic stress disorder and post-traumatic stress symptoms
      following birth occur amongst a small proportion of women but can lead to poor
      maternal mental health, impairment in mother-infant bonding and relationship
      stress. This integrative review aims to examine the associated risk factors and
      women's own experiences of postnatal post-traumatic stress in order to better
      understand this phenomenon. METHOD: Fifty three articles were included and
      critically reviewed using the relevant Critical Appraisal Skills Program
      checklists or Strengthening the Reporting of Observational studies in
      Epidemiology assessment tool. FINDINGS: Risk factors for postnatal post-traumatic
      stress symptoms and disorder include factors arising before pregnancy, during the
      antenatal period, in labour and birth and in the postnatal period. Potential
      protective factors against postnatal post-traumatic stress have been identified
      in a few studies. The development of postnatal post-traumatic stress can lead to
      negative outcomes for women, infants and families. DISCUSSION: Risk factors for
      post-traumatic stress symptoms and disorder are potentially identifiable pre
      pregnancy and during the antenatal, intrapartum and postnatal periods. Potential
      protective factors have been identified however they are presently under
      researched. Predictive models for postnatal post-traumatic stress disorder
      development have been proposed, however further investigation is required to test
      such models in a variety of settings. CONCLUSIONS: Postnatal post-traumatic
      stress symptoms and disorder have been shown to negatively impact the lives of
      childbearing women. Further investigation into methods and models for identifying
      women at risk of developing postnatal post-traumatic stress following childbirth
      is required in order to improve outcomes for this population of women.

PMID- 29337006
TI  - Relation Between Dietary Essential Fatty Acid Intake and Dry Eye Disease and
      Meibomian Gland Dysfunction in Postmenopausal Women.
AB  - PURPOSE: To evaluate the relationship between omega-3 (n-3) and omega-6 (n-6)
      fatty acids with dry eye disease (DED) and meibomian gland dysfunction (MGD).
      DESIGN: Cross-sectional study. METHODS: Postmenopausal women (n = 439) underwent
      a clinical evaluation and completed the Vio Food Frequency Questionnaire to
      estimate their dietary intake of n-3s and n-6s. Subjects were categorized into 2
      binary classifications based on whether or not they had (1) DED and (2) MGD. Mean
      intake of dietary fatty acids was compared with 2-sample t tests. Univariate
      logistic regression models were used to estimate the odds ratios for each
      condition associated with each quintile of n-3s, n-6s, and n-6:n-3 ratios.
      RESULTS: For DED vs non-DED, there were no significant differences in n-3 intake
      (1.95 +/- 1.47 g vs 1.92 +/- 1.24 g, P = .86), n-6 intake (15.58 +/- 11.56 g vs
      15.44 +/- 10.61 g, P = .91), and n-6:n-3 (8.30 +/- 2.57 vs 8.30 +/- 2.57, P =
      .99). For MGD vs non-MGD, there were no significant differences in n-3 intake
      (1.87 +/- 1.35 vs 1.96 +/- 1.39, P = .61), n-6 intake (15.26 +/- 11.85 vs 15.62
      +/- 10.93, P = .80), and n-6:n-3 (8.35 +/- 2.94 vs 8.28 +/- 2.42, P = .84). The
      odds ratios (OR) for DED did not differ significantly from 1.0 for n-3, n-6, or n
      6:n-3. High n-3 consumption (OR = 0.22 [0.06-0.78]) and moderate n-6 consumption
      (OR = 0.37 [0.15-0.91]) were associated with a decreased frequency of MGD.
      CONCLUSIONS: Dietary consumption of n-3s and n-6s showed no association with DED,
      but high n-3 consumption and moderate n-6 consumption were protective against MGD
      in this large sample of postmenopausal women.

PMID- 29337008
TI  - Ice pack induced perineal analgesia after spontaneous vaginal birth: Randomized
      controlled trial.
AB  - BACKGROUND: Ice-pack is widely used for alleviating postpartum perineal pain
      sustained after birth related perineal trauma. However, it lacks robust evidence
      on timing and frequency of applications, to ensure the effective and safe use of
      this therapy. AIMS: To evaluate if a 10min ice-pack application relieved
      postpartum perineal pain and if the analgesic effect was maintained for up to 2h.
      METHODS: A randomised controlled trial conducted from December 2012 to February
      2013 with 69 primiparous women >=18 years old, 6-24h postpartum, with perineal
      pain >=3, who had not received anti-inflammatory medication or analgesics after
      childbirth, who were randomised to a single ice-pack application on the perineum
      for 10min or standard care. The primary and secondary outcomes were a reduction
      >=30% in perineal pain intensity, immediately after the application and the
      maintenance of the analgesic effect for up to 2h, respectively. FINDINGS:
      Immediately post-intervention, the proportion of women whose perineal pain
      decreased >=30% was significantly higher in the experimental group. Within 2h,
      there was no significant difference in the pain levels in both groups. Within 2h,
      for 61.9% and 89.3% of women in the experimental and control group, respectively,
      the perineal pain levels remained unchanged. For the remaining participants,
      perineal pain was increasing after an average time of 1h 45min and 1h 56min for
      the experimental and control groups, respectively. CONCLUSION: By applying an ice
      pack for 10min to the perineum, effective pain relief is achieved, that is
      maintained for between 1h 45min and 2h.

PMID- 29337009
TI  - Coherence and interlimb force control: Effects of visual gain.
AB  - Neural coupling across hemispheres and homologous muscles often appears during
      bimanual motor control. Force coupling in a specific frequency domain may
      indicate specific bimanual force coordination patterns. This study investigated
      coherence on pairs of bimanual isometric index finger force while manipulating
      visual gain and task asymmetry conditions. We used two visual gain conditions
      (low and high gain = 8 and 512 pixels/N), and created task asymmetry by
      manipulating coefficient ratios imposed on the left and right index finger forces
      (0.4:1.6; 1:1; 1.6:0.4, respectively). Unequal coefficient ratios required
      different contributions from each hand to the bimanual force task resulting in
      force asymmetry. Fourteen healthy young adults performed bimanual isometric force
      control at 20% of their maximal level of the summed force of both fingers. We
      quantified peak coherence and relative phase angle between hands at 0-4, 4-8, and
      8-12 Hz, and estimated a signal-to-noise ratio of bimanual forces. The findings
      revealed higher peak coherence and relative phase angle at 0-4 Hz than at 4-8 and
      8-12 Hz for both visual gain conditions. Further, peak coherence and relative
      phase angle values at 0-4 Hz were larger at the high gain than at the low gain.
      At the high gain, higher peak coherence at 0-4 Hz collapsed across task asymmetry
      conditions significantly predicted greater signal-to-noise ratio. These findings
      indicate that a greater level of visual information facilitates bimanual force
      coupling at a specific frequency range related to sensorimotor processing.

PMID- 29337011
TI  - The genus Opisthacanthus Peters, 1861 (Scorpiones: Hormuridae), a remarkable
      Gondwanian group of scorpions.
AB  - New comments are proposed on the geographic distribution of genus Opisthacanthus,
      and the Gondwanian model is further supported. The diversity of the genus is
      extraordinary in Madagascar, with the same number of species as in continental
      Africa, but sub-Saharan Africa is home to six out of the nine groups currently
      recognized of Opisthacanthus. Given the affinities of the Opisthacanthus groups
      and their current distribution, a center of origin in Africa could be favored for
      these ancient scorpions. The proposed Gondwana model suggests that the Madagascar
      Opisthacanthus are closer to those of the New World, which is consistent with the
      affinities observed in morphological characters. A new species, Opisthacanthus
      titanus sp. n., is described from the Torotorofotsy Forest, located in Eastern
      Madagascar. The new species shows affinities with both Opisthacanthus
      madagascariensis Kraepelin, 1894 known from dry regions in the western portion of
      the island and Opisthacanthus lavasoa Lourenco, Wilme & Waeber, 2016 only known
      from the extreme southeast of the island. The new species and O. madagascariensis
      have similar external morphologies but the morphometric values are markedly
      distinct. Moreover, O. madagascariensis is exclusively found in spiny forest
      thickets and open woodlands, whereas the new species was found in the humid
      forest of Torotorofotsy. The total number of species in Madagascar is now raised
      to twelve. Biogeographical scenarios are also proposed to infer the origin of the
      Opisthacanthus and better understand its distribution in the New World, in Africa
      and Madagascar.

PMID- 29337010
TI  - Protective effects of a radical scavenger edaravone on oligodendrocyte precursor
      cells against oxidative stress.
AB  - Oligodendrocyte precursor cells (OPCs) play critical roles in maintaining the
      number of oligodendrocytes in white matter. Previously, we have shown that
      oxidative stress dampens oligodendrocyte regeneration after white matter damage,
      while a clinically proven radical scavenger, edaravone, supports oligodendrocyte
      repopulation. However, it is not known how edaravone exerts this beneficial
      effect against oxidative stress. Using in vivo and in vitro experiments, we have
      examined whether edaravone exhibits direct OPC-protective effects. For in vivo
      experiments, prolonged cerebral hypoperfusion was induced by bilateral common
      carotid artery stenosis in mice. OPC damage was observed on day 14 after the
      onset of cerebral hypoperfusion, and edaravone was demonstrated to decrease OPC
      death in cerebral white matter. In vitro experiments also confirmed that
      edaravone reduced oxidative-stress-induced OPC death. Because white matter damage
      is a major hallmark of many neurological diseases, and OPCs are instrumental in
      white matter repair after injury, our current study supports the idea that
      radical scavengers may provide a potential therapeutic approach for white matter
      related diseases.

PMID- 29337012
TI  - Expanding the limits of endoscopic intraorbital tumor resection using 3
      dimensional reconstruction.
AB  - INTRODUCTION: Endoscopic orbital surgery is a nascent field and new tools are
      required to assist with surgical planning and to ascertain the limits of the
      tumor resectability. OBJECTIVE: We purpose to utilize three-dimensional
      radiographic reconstruction to define the theoretical lateral limit of endoscopic
      resectability of primary orbital tumors and to apply these boundary conditions to
      surgical cases. METHODS: A three-dimensional orbital model was rendered in 4
      representative patients presenting with primary orbital tumors using OsiriX open
      source imaging software. A 2-Dimensional plane was propagated between the
      contralateral nare and a line tangential to the long axis of the optic nerve
      reflecting the trajectory of a trans-septal approach. Any tumor volume falling
      medial to the optic nerve and/or within the space inferior to this plane of
      resectability was considered theoretically resectable regardless of how far it
      extended lateral to the optic nerve as nerve retraction would be unnecessary.
      Actual tumor volumes were then superimposed over this plan and correlated with
      surgical outcomes. RESULTS: Among the 4 lesions analyzed, two were fully medial
      to the optic nerve, one extended lateral to the optic nerve but remained inferior
      to the plane of resectability, and one extended both lateral to the optic nerve
      and superior to the plane of resectability. As predicted by the three-dimensional
      modeling, a complete resection was achieved in all lesions except one that
      transgressed the plane of resectability. No new diplopia or vision loss was
      observed in any patient. CONCLUSION: Three-dimensional reconstruction enhances
      preoperative planning for endoscopic orbital surgery. Tumors that extend lateral
      to the optic nerve may still be candidates for a purely endoscopic resection as
      long as they do not extend above the plane of resectability described herein.

PMID- 29337013
TI  - Inferior turbinectomy: what is the best technique?

PMID- 29337014
TI  - The anatomic analysis of the vidian canal and the surrounding structures
      concerning vidian neurectomy using computed tomography scans.
AB  - INTRODUCTION: The type of endoscopic approach chosen for vidian neurectomy can be
      specified by evaluating the vidian canal and the surrounding sphenoid sinus
      structures. OBJECTIVE: The variations and morphometry of the vidian canal were
      investigated, focusing on the functional correlations between them which are
      crucial anatomical landmarks for preoperative planning. METHODS: This study was
      performed using paranasal multidetector computed tomography images that were
      obtained with a section thickening of 0.625mm of 250 adults. RESULTS: The
      distributions of 500 vidian canal variants were categorized as follows; Type 1,
      within the sphenoid corpus (55.6%); Type 2, partially protruding into the
      sphenoid sinus (34.8%); Type 3, within the sphenoid sinus (9.6%). The
      pneumatization of the pterygoid process is mostly seen in vidian canal Type 2
      (72.4%) and Type 3 (95.8%) (p<0.001). The mean distances from the vidian canal to
      the foramen rotundum and the palatovaginal canal were greater in the vidian canal
      Type 2 and 3 with the pterygoid process pneumatization (p<0.001). The prevalence
      of the intrasphenoid septum between the vidian canal and the vomerine crest and
      lateral attachment which ending on carotid prominence were much higher in vidian
      canal Type 3 than other types (p<0.001). The mean angle between the posterior end
      of the middle turbinate and the lateral margin of the anterior opening of the
      vidian canal was measured as 33.05+/-7.71 degrees . CONCLUSIONS: Preoperative
      radiologic analysis of the vidian canal and the surrounding structures will allow
      surgeons to choose an appropriate endoscopic approach to ensure predictable
      postoperative outcomes.

PMID- 29337015
TI  - Improved quantitative fatty acid values with correction of T2 relaxation time in
      terminal methyl group: In vivo proton magnetic resonance spectroscopy at ultra
      high field in hepatic steatosis.
AB  - Proton magnetic resonance spectroscopy (MRS) with optimized relaxation time is an
      effective method to quantify hepatic fatty acid values and characterize
      steatosis. The aim of this study is to quantify the difference in hepatic lipid
      content with metabolic changes during the progression of steatosis by using
      localized MRS sequence with T2 relaxation time determination. Fatty liver disease
      was induced in C57BL/6N mice through a high-fat diet (HFD) of pellets containing
      60% fat, 20% protein, and 20% carbohydrates. We used stimulated echo acquisition
      mode (repetition time: 3500 ms; mixing time: 10 ms; echo time: 20 ms) sequence.
      Using enhanced and mono exponential curve-fitting methods, the lipid relaxation
      time in mice was estimated at a fixed repetition time of 5000 ms and echo time
      ranging from 20 to 70 ms. The calculated lipid contents with incorrect and
      correct relaxation times were as follows: total saturated fatty acid (4.00 +/-
      2.90 vs 6.74 +/- 2.25, p < 0.05 at week 0; 15.23 +/- 9.94 vs 25.53 +/- 10.49, p <
      0.05 at week 4); total unsaturated fatty acid (0.40 +/- 0.49 vs 0.56 +/- 0.47, p
      < 0.05 at week 4; 0.33 +/- 0.26 vs 0.60 +/- 0.21, p < 0.01 at week 7); total
      unsaturated bond (0.48 +/- 0.52 vs 1.05 +/- 0.58, p < 0.05 at week 10).
      Furthermore, we determined that the correct relaxation times of triglycerides
      between 0 and 10 weeks were significantly altered in the resonances (~2.03 ppm:
      31.07 +/- 1.00 vs 27.62 +/- 1.20, p < 0.01; ~2.25 ppm: 29.10 +/- 1.52 vs 26.39 +/
      1.08, p < 0.05; ~2.78 ppm: 37.67 +/- 2.92 vs 29.37 +/- 2.64, p < 0.001). The
      work presented focused on the significance of the J-coupling effect. The
      selection of an appropriate relaxation time considering the J-coupling effect
      provides an effective method for quantifying lipid contents and characterizing
      hepatic steatosis.

PMID- 29337017
TI  - Management of diabetes in older adults.
AB  - Type 2 diabetes prevalence is high in older adults and is expected to rise in the
      next decades. Diabetes in the population of frail older adults is accompanied by
      functional disability, several comorbidities, and premature mortality. A
      comprehensive geriatric assessment, including functional, cognitive, mental and
      social status, is advisable for identifying the glycemic targets and glucose
      lowering therapies, focused on patient preferences, needs, and risks. The
      therapeutic options for older adults with diabetes are like those for the adult
      population. However, the pharmacological treatments must be carefully prescribed
      and monitored, taking into consideration the patient cognitive capacities, the
      potentially life-threatening drug-drug interactions, the cardiovascular risk, and
      with the main goal of avoiding hypoglycemia. Also, a careful nutritional
      evaluation with appropriate tools, as well as a balanced and periodically
      monitored physical activity, contribute to an effective tailored care plan, as
      needed by older adults with diabetes. This review evaluates the currently
      available hypoglycemic drugs and the current indications to the Italian
      diabetology community, specifically with regard to the treatment of adults aged
      75 years or older with diabetes, including the unmet needs by the guidelines.

PMID- 29337016
TI  - Tear instability importance, mechanisms, validity and reliability of assessment.
AB  - PURPOSE: To examine the factors which contribute to tear stability and the
      validity and reliability of methods used for assessing tear break up time which
      is a core part of an examination of tear stability in dry eye patients. METHODS:
      A review of publications which are relevant to tear stability and its assessment.
      RESULTS: Tear break up time may be more invasive than intended if difficulty
      avoiding blinking during assessment results in reflex tearing. Notwithstanding
      control of instilled volume and concentration of fluorescein, on-eye dilution is
      highly variable according to resident tear volume. Blinking to evenly distribute
      fluorescein may improve tear and lipid layer thickness so habitual tear function
      is not assessed. Emphasis on a role for Meibomian gland dysfunction as a cause of
      tear instability may be appropriate in many cases but ignores the roles for other
      sources of tear lipid and other non-lipid contributions to tear instability such
      as aqueous or mucus deficiency, desiccated epitheliopathy or anomalous blinking.
      Objective less-invasive methods eliminate problems of inter-observer variability
      and can reliably 'maintain vigilance' over wide areas of the tear layer. However
      less-invasive results to date include mean tear break up findings which are both
      shorter and longer than expected for normal controls. CONCLUSIONS: Fluorescein
      tear break up time assessments cannot be standardised and less-invasive methods
      are not yet standardised. Objective less-invasive and subjective fluorescein
      break up time tests do not appear to be measuring the same tear phenomena
      although both should be performed before other invasive procedures.

PMID- 29337018
TI  - Prevalence of and secular trends in diagnosed diabetes in Italy: 1980-2013.
AB  - BACKGROUND AND AIMS: The aim of this research was to examine the prevalence of
      diabetes in Italy over a 34-year period. METHODS AND RESULTS: Self-reported
      diabetes was assessed in eight health interview surveys of representative samples
      of Italian population aged 20 years and over. Crude and standardised prevalence
      were calculated by age, sex, educational level and area of residence. Logistic
      models were fitted to calculate the contribution of age and BMI to the trend in
      prevalence. In 2013 nearly 3.4 million Italians had a diagnosis of diabetes, more
      than twice as many as in 1980. The crude prevalence of diabetes in men rose from
      3.3% in 1980 to 7.1% in 2013 (+115%), and from 4.7% to 6.8% in women (+45%). The
      prevalence was almost stable during the eighties, and started to rise from the
      beginning of the nineties. One third of the increase in men and two thirds in
      women is due to the ageing of the population, since the age-standardised
      prevalence increased by 79% in men and 14% in women. The prevalence of overweight
      and obesity increased less steeply than diabetes, and their contribution to the
      trend in diabetes is less relevant than age. Prevalence rose more in the elderly,
      in low-educated men, and in high-educated women. CONCLUSION: Given that the
      ageing population plays a considerable role in explaining the trend, and that the
      number of people in the oldest age groups will continue to grow, the rise in the
      number of individuals with diabetes will represent a severe challenge for the
      national health system.

PMID- 29337019
TI  - Prediabetes is associated with microalbuminuria, reduced kidney function and
      chronic kidney disease in the general population: The KORA (Cooperative Health
      Research in the Augsburg Region) F4-Study.
AB  - BACKGROUND AND AIMS: We investigated the associations of serum fasting (FG) and 2
      h postload (2HG) glucose from an oral glucose tolerance test (OGTT), glycated
      hemoglobin (HbA1c), fasting insulin and the homeostasis model assessment-insulin
      resistance index (HOMA-IR) with urinary albumin-to-creatinine ratio (ACR) and
      estimated glomerular filtration rate (eGFR). METHODS AND RESULTS: We performed
      cross-sectional analyses of 2713 subjects (1429 women; 52.7%) without known type
      2 diabetes, aged 31-82 years, from the KORA (Cooperative Health Research in the
      Augsburg Region) F4-Study. FG, 2HG, HbA1c, fasting insulin, HOMA-IR and glucose
      tolerance categories were analyzed for association with ACR and eGFR in
      multivariable adjusted linear and median regression models, and with isolated
      microalbuminuria (i-MA), isolated reduced kidney function (i-RKF) and chronic
      kidney disease (CKD, defined as MA and/or RKF) in multivariable adjusted logistic
      regression models. Among the 2713 study participants, 28% revealed prediabetes
      (isolated impaired fasting glucose [i-IFG], isolated glucose tolerance [i-IGT] or
      both by American Diabetes Association definition), 4.2% had unknown type 2
      diabetes, 6.5% had i-MA, 3.1% i-RKF and 10.9% CKD. In multivariable adjusted
      analysis, all continuous variables (FG, 2HG, HbA1c, fasting insulin and HOMA-IR)
      were associated with i-MA, i-RKF and CKD. The odds ratios (ORs) for i-MA and CKD
      were 1.54 (95% confidence interval: 1.02-2.33) and 1.58 (1.10-2.25) for
      individuals with i-IFG. Moreover, the OR for i-RKF was 2.57 (1.31-5.06) for
      individuals with IFG + IGT. CONCLUSION: Our findings suggest that prediabetes
      might have harmful effects on the kidney.

PMID- 29337020
TI  - Inverse association between plasma homocysteine concentrations and type 2
      diabetes mellitus among a middle-aged and elderly Chinese population.
AB  - BACKGROUND AND AIMS: Plasma homocysteine concentrations have been reported to be
      associated with type 2 diabetes mellitus (T2DM) with controversial findings. The
      aim of the present study was to investigate the association between plasma
      homocysteine concentrations and T2DM. METHODS AND RESULTS: A cross-sectional
      study including 19,085 eligible participants derived from the Dongfeng-Tongji
      cohort was conducted. Plasma homocysteine concentrations were measured by Abbott
      Architect i2000 Automatic analyzer and T2DM was defined according to American
      Diabetes Association criteria. Logistic regression model was used to explore the
      association between plasma homocysteine concentrations and T2DM. The prevalence
      of T2DM was 19.0% in the whole population (mean age 62.9 years), 21.8% in males,
      and 17.1% in females. In the multivariable logistic regression analyses, compared
      with those in the lowest quintile, the OR (95% CI) of T2DM was 1.05 (0.92-1.21),
      0.99 (0.86-1.14), 0.90 (0.78-1.05), and 0.77 (0.66-0.90) for quintile 2 to
      quintile 5 of homocysteine concentrations after adjustment for potential
      confounders (P for trend < 0.0001). Homocysteine concentrations were associated
      with decreased T2DM prevalence risk (OR = 0.88 per SD increase of homocysteine
      concentration; 95% CI: 0.84-0.93). A significant interaction between homocysteine
      concentrations and drinking status on T2DM prevalence risk was observed (P for
      interaction = 0.03). The inverse association of plasma homocysteine
      concentrations with T2DM prevalence risk was observed in non-drinkers but not in
      current drinkers. CONCLUSION: Plasma homocysteine concentrations were inversely
      correlated with T2DM among a middle-aged and elderly Chinese population.

PMID- 29337021
TI  - Changing Physical Activity Behavior in People With Multiple Sclerosis: A
      Systematic Review and Meta-Analysis.
AB  - OBJECTIVES: To (1) systematically review the literature on behavioral
      interventions for people with multiple sclerosis (MS) that aim to change physical
      activity (PA) behavior; and (2) explore whether these interventions are
      clinically effective in improving PA, are theory based, and use established
      behavior change techniques (BCTs). DATA SOURCES: A systematic electronic search
      was conducted on databases EBSCO (including AMED, Biomedical Reference
      Collection: Expanded, CINHAL, MEDLINE, PsycArticles, PsycInfo), PubMed, EMBASE,
      and Web of Science from April 2017 to May 2017. STUDY SELECTION: Studies were
      included if (1) the interventions aimed to change PA behavior among people with
      MS; (2) PA was recognized as a primary outcome measure; and (3) they had a
      randomized controlled trial (RCT) design. DATA EXTRACTION: The resulting
      behavioral interventions were coded using the Theory Coding Scheme and the CALO
      RE taxonomy to assess theory base and BCTs. A meta-analysis was conducted to
      assess effectiveness. DATA SYNTHESIS: Fourteen RCTs were included. Combined,
      there was a significant (P=.0003; d=1.00; 95% confidence interval, .46-1.53)
      short-term change in self-report PA behavior for studies with nonactive control
      groups. There was no change in objective or long-term PA. Studies failed to
      discuss results in relation to theory and did not attempt to refine theory. Fifty
      percent of BCTs within the CALO-RE were used, with BCTs of "goal-setting" and
      "action-planning" being the most frequently used. CONCLUSIONS: Current evidence
      supports the efficacy of PA intervention on subjective but not objective
      outcomes. However, conclusions from this review should be interpreted with
      caution because of the small number of studies included and small sample size.
      Further, while using theory in intervention design, interventions in this review
      have not reported the refining of theory. Exploration of the use of additional
      BCTs to change PA behavior is also required within future interventions.

PMID- 29337022
TI  - Reaction Time and Joint Kinematics During Functional Movement in Recently
      Concussed Individuals.
AB  - OBJECTIVE: To compare movement reaction time and joint kinematics between
      athletes with recent concussion and matched control recreational athletes during
      3 functional tasks. DESIGN: Cross-sectional. SETTING: Laboratory. PARTICIPANTS:
      College-aged recreational athletes (N=30) comprising 2 groups (15 participants
      each): (1) recent concussion group (median time since concussion, 126d; range, 28
      432d) and (2) age- and sex-matched control group with no recent concussions.
      INTERVENTIONS: We investigated movement reaction time and joint kinematics during
      3 tasks: (1) jump landing, (2) anticipated cut, and (3) unanticipated cut. MAIN
      OUTCOME MEASURES: Reaction time and reaction time cost (jump landing reaction
      time-cut reaction time/jump landing reaction time*100%), along with trunk, hip,
      and knee joint angles in the sagittal and frontal planes at initial ground
      contact. RESULTS: There were no reaction time between-group differences, but the
      control group displayed improved reaction time cost (10.7%) during anticipated
      cutting compared with the concussed group (0.8%; P=.030). The control group
      displayed less trunk flexion than the concussed group during the nondominant
      anticipated cut (5.1 degrees  difference; P=.022). There were no other kinematic
      between-group differences (P>=.079). CONCLUSIONS: We observed subtle reaction
      time and kinematic differences between individuals with recent concussion and
      those without concussion more than a month after return to activity after
      concussion. The clinical interpretation of these findings remains unclear, but
      may have future implications for postconcussion management and rehabilitation.

PMID- 29337023
TI  - The Effects of Functional Training, Bicycle Exercise, and Exergaming on Walking
      Capacity of Elderly Patients With Parkinson Disease: A Pilot Randomized
      Controlled Single-blinded Trial.
AB  - OBJECTIVES: To compare the effects of functional training, bicycle exercise, and
      exergaming on walking capacity of elderly with Parkinson disease (PD). DESIGN: A
      pilot randomized, controlled, single-blinded trial. SETTING: A state reference
      health care center for elderly, a public reference outpatient clinic for the
      elderly. PARTICIPANTS: Elderly individuals (>=60 years of age; N=62) with
      idiopathic PD (stage 2 to 3 of modified Hoehn and Yahr staging scale) according
      to the London Brain Bank. INTERVENTION: The participants were randomly assigned
      to three groups. Group 1 (G1) participated in functional training (n=22); group 2
      (G2) performed bicycle exercise (n=20), and group 3 (G3) trained with Kinect
      Adventures (Microsoft, Redmond, WA) exergames (n=20). MAIN OUTCOME MEASURES: The
      primary outcome measure was the 6-minute walk test (6MWT); secondary outcome
      measures were the 10-m walk test (10MWT), sitting-rising test (SRT), body mass
      index, Parkinson Disease Questionnaire-39, World Health Organization Disability
      Assessment Schedule 2.0 (WHODAS 2.0), and 15-item Geriatric Depression Scale.
      RESULTS: All groups showed significant improvements in 6MWT (G1 P=.008; G2
      P=.001; G3 P=.005), SRT (G1 P<.001; G2 P=.001; G3 P=.003), and WHODAS 2.0 (G1
      P=.018; G2 P=.019; G3 P=.041). Only G3 improved gait speed in 10MWT (P=.11). G1
      (P=.014) and G3 (P=.004) improved quality of life. No difference was found
      between groups. CONCLUSIONS: Eight weeks of exergaming can improve the walking
      capacity of elderly patients with PD. Exergame training had similar outcomes
      compared with functional training and bicycle exercise. The three physical
      exercise modalities presented significant improvements on walking capacity,
      ability to stand up and sit, and functionality of the participants.

PMID- 29337024
TI  - Moderators of Treatment Outcomes After Telehealth Self-Management and Education
      in Adults With Multiple Sclerosis: A Secondary Analysis of a Randomized
      Controlled Trial.
AB  - OBJECTIVE: To examine moderators of treatment effects in a randomized controlled
      trial comparing a telehealth self-management intervention with a telehealth
      multiple sclerosis (MS) education intervention for fatigue, pain, and mood in
      adults with MS. DESIGN: Secondary analysis of a single-blind randomized
      controlled trial. SETTING: Community. PARTICIPANTS: Adults with MS and chronic
      fatigue, chronic pain, and/or moderate depressive symptoms (N=163) recruited from
      across the United States. INTERVENTIONS: Two 8-week, telephone-delivered symptom
      interventions delivered 1:1: a self-management intervention (n=75) and an MS
      education intervention (n=88). MAIN OUTCOME MEASURES: Outcome measures were
      fatigue impact pain interference, and depressive symptom severity assessed at
      baseline and posttreatment. Potential moderators of treatment effects assessed at
      baseline were demographics (age, sex, and education), clinical characteristics
      (disease duration and disability severity), symptoms (perceived cognitive
      impairment and pain intensity), baseline levels of the treatment outcomes (pain
      interference, fatigue impact and depressive symptom severity), and cognitive
      behavioral factors (pain catastrophizing, fatigue catastrophizing, self-efficacy,
      and patient activation). RESULTS: Moderation analyses found significant
      moderation for fatigue impact but not for pain intensity or depressive symptom
      severity. Baseline patient activation interacted with treatment group to predict
      fatigue impact at posttreatment (P=.049). Among participants with high baseline
      patient activation, the self-management group reported significantly less fatigue
      at posttreatment than the education group. No other variables moderated the study
      outcomes. CONCLUSIONS: At the group level, participants responded to both
      interventions, regardless of disease characteristics, demographics, symptom
      levels, and cognitive behavioral factors. Self-management and education are both
      potentially beneficial symptom treatments that may be recommended to individuals
      with MS and chronic pain, fatigue, and/or depressive symptoms.

PMID- 29337025
TI  - Hepatosplenic T-cell Lymphoma: a review of clinicopathologic features,
      pathogenesis, and prognostic factors.
AB  - Hepatosplenic T-cell lymphoma (HSTCL) is a rare and clinically aggressive type of
      T-cell lymphoma that arises most often in adolescents and young adults. Patients
      with HSTCL commonly present with B-symptoms and cytopenias, which may suggest a
      diagnosis of acute leukemia initially. Patients present with extranodal disease
      involving the spleen, liver and bone marrow; lymphadenopathy is usually absent.
      The lymphoma cells can show a spectrum of cell sizes and are of T-cell lineage,
      often negative for CD4 and CD8 and positive for T-cell receptor gammadelta or,
      less often, alphabeta. Recent studies have identified gene mutations in oncogenic
      pathways that are likely involved in pathogenesis and may be targets for therapy.
      Mutations in STAT3 or STAT5B lead to activation of the JAK/STAT pathway, and
      mutations involving SETD2, IN080 and ARID1 are involved in chromatin
      modification. Currently, there is no consensus standard of care for HSTCL
      patients, although several studies support a role for allogeneic hematopoietic
      stem cell transplant. Although patients with HSTCL are best treated in the
      context of clinical trials, the rarity of these neoplasms likely necessitates a
      multi-institutional approach. In this review, we focus on the clinicopathologic
      and genetic characteristics of HSTCL. We also discuss the differential diagnosis
      and therapeutic approaches.

PMID- 29337026
TI  - Effect of recombinant human growth hormone on rotator cuff healing after
      arthroscopic repair: preliminary result of a multicenter, prospective,
      randomized, open-label blinded end point clinical exploratory trial.
AB  - BACKGROUND: This study evaluated the effect of systemic injection of recombinant
      human growth hormone (rhGH) on outcomes after arthroscopic rotator cuff repair.
      METHODS: This multicenter, prospective, randomized, comparative trial, randomized
      patients who underwent arthroscopic repair of large-sized rotator cuff tears into
      3 groups: rhGH 4 mg group (n = 26), rhGH 8 mg group (n = 24) , and control group
      (n = 26). Sustained release rhGH was injected subcutaneously once weekly for 3
      months postoperatively. The healing failure rate (primary end point), fatty
      infiltration, and atrophy of the supraspinatus muscle, and functional scores
      (Constant and American Shoulder and Elbow Surgeons scores) were evaluated at 6
      months. Range of motion, pain visual analog scale, and serum insulin-like growth
      factor-1 level were measured at each follow-up. RESULTS: The healing failure rate
      was similar between groups (rhGH 4 mg group, 30.8%; rhGH 8 mg group, 16.7%; and
      control group, 34.6%; all P > .05) The proportion of severe fatty infiltration
      (Goutallier grade >=3) was 20.8% in the rhGH 8 mg group, 23.1% in the rhGH 4 mg
      group, and 34.6% in the control group (P > .05). Functional outcomes, range of
      motion, and pain visual analog scale were similar between groups (all P > .05).
      The rhGH 8 mg group showed more increased peak insulin-like growth factor-1 level
      (279.43 ng/mL) than the rhGH 4 mg group ((196.82 ng/mL) and control group (186.31
      ng/mL), which was not statistically different (all P > .05). No rhGH injection
      related major safety issues occurred. CONCLUSIONS: This preliminary study showed
      no statistically significant improvement in healing or outcomes related to the
      treatment of rhGH after rotator cuff repair. However, further study with more
      enrolled patients after resetting the rhGH dose or daily administration protocol
      would be mandatory.

PMID- 29337027
TI  - An assessment of proximal humerus density with reference to stemless implants.
AB  - BACKGROUND: Shoulder arthroplasty humeral components have undergone several
      generational changes, with systems now offering shorter stems and stemless
      options. The stemless humeral implants obtain fixation in the trabecular bone of
      the proximal humerus through elaborate fixation features. To optimize implant
      design, the regional variations in bone density within the proximal humerus
      should be determined. As such, the purpose of this computed tomography-based
      study was to map the regional variations in bone density of the proximal humerus.
      METHODS: The trabecular-canal of the proximal humerus was extracted from computed
      tomography scans of 98 subjects and divided into 13 slices and 5 subsections
      (central, anterior, posterior, medial, and lateral). The average apparent density
      (rhoAVG) was then quantified in each subsection of the trabecular-canal. RESULTS:
      Slice depth, subsection, and gender were all significant main effects, with
      additional significant interactions between slice depth, subsection, and
      osteoarthritic condition. The slices above the resection plane had the greatest
      rhoAVG, with densities decreasing down the canal. The central subsection had
      significantly lower rhoAVG than the peripheral sections, and the medial
      subsection tended to have the highest rhoAVG (P < .001). Furthermore, the rhoAVG
      of male subjects was significantly greater than that of female subjects (P <
      .001). CONCLUSIONS: The apparent density of the proximal humerus' trabecular
      canal is nonuniform. This has implications for the design of stemless implants,
      indicating that implants seeking purchase in higher density bone should take
      advantage of the peripheral regions of the trabecular-canal within the first 15
      20 mm beneath the humeral head resection plane.

PMID- 29337028
TI  - Bipolar pedicled teres major transfer for irreparable subscapularis tendon tears:
      an anatomic feasibility study.
AB  - BACKGROUND: Subscapularis (SSC) tendon tears are a challenging problem because
      they can significantly alter shoulder mechanics and function. Tendon retraction
      and advanced fatty degeneration associated with a chronic tear may make it
      irreparable. Tendon transfers options for such tears are viable, but results in
      the setting of associated glenohumeral instability are inconsistent. With the
      potential to recreate the SSC line of pull, the teres major (TM) may be a viable
      option for transfer. This cadaveric study investigated the feasibility and
      outlined the steps of a bipolar, pedicled TM transfer for irreparable SSC tendon
      tears. METHODS: Eight fresh frozen cadaver torsos from 4 women and 4 men (average
      age, 84 years; range, 68-96 years) were dissected. Anatomic details comparing TM
      to SSC were examined, including muscle width, length, thickness, and line of pull
      in the scapular plane. In addition, a surgical technique was described for
      implementing the pedicled TM transfer. RESULTS: Measurements between the TM and
      SSC were comparable, with the exception of muscle belly width, which was
      significantly greater in the SSC. With transfer of the TM, there was no
      impingement or tension on the brachial plexus or the neurovascular pedicle of the
      TM. The line of pull of the TM relative to the SSC had a difference of 9 degrees
      . CONCLUSIONS: This study demonstrates that a bipolar TM tendon transfer is an
      anatomically feasible option for reconstruction of an irreparable SSC tendon
      tear. Further clinical studies are necessary to understand its outcome in in vivo
      conditions.

PMID- 29337029
TI  - Arthroscopic Latarjet procedure with double-button fixation: short-term
      complications and learning curve analysis.
AB  - BACKGROUND: The arthroscopic Latarjet with double-button fixation is a guided
      procedure recently proposed to treat anterior shoulder instability with glenoid
      bone loss. The goal of this study was to report intraoperative and early
      postoperative complications and to analyze the learning curve. METHODS: This was
      a prospective, nonrandomized study that included 88 patients. Intraoperative or
      postoperative complications as well as adverse events and operative time were
      recorded. Clinical outcomes were evaluated at 2 weeks, 1.5 months, and at the
      last follow-up. Radiologic analysis was based on an immediate postoperative
      computed tomography scan. RESULTS: The intraoperative complications or adverse
      events rate was 3.3%: 1 conversion to open surgery, 1 bone block fracture, and 1
      instrumentation problem. The postoperative complication rate was 6.8%: 4 coracoid
      migrations, and 2 subluxations. None of these complications occurred beyond the
      10th case performed. The average operative time significantly decreased with
      surgical experience (r = -0.8426; 95% confidence interval, -0.9074 to -0.7384; P
      < .0001) to reach 76 +/- 12 minutes (range, 62-95 minutes) at 30 cases.
      Radiologically, 90% of the bone blocks were flush and subequatorial beyond the
      30th case. At a mean follow-up of 12.6 months (range, 6-24 months), Walch-Duplay
      and Rowe scores were 80 and 81 points, respectively. CONCLUSIONS: At short-term
      follow-up, the arthroscopic Latarjet procedure with double-button fixation
      exhibited a low complication rate. Operative time significantly improved with
      surgical experience and was optimized after 30 cases. Early clinical results
      confirmed that this procedure can be safe and reliable.

PMID- 29337030
TI  - Nasal IL-25 predicts the response to oral corticosteroids in chronic
      rhinosinusitis with nasal polyps.

PMID- 29337031
TI  - Does vagus nerve stimulation influence pregnancy outcomes?

PMID- 29337032
TI  - Biohydrogen fermentation of galactose at various substrate concentrations in an
      immobilized system and its microbial correspondence.
AB  - The effects of substrate concentration on fermentative hydrogen production from
      galactose at a fixed hydraulic retention time of 12 h were investigated in an
      immobilized continuously stirred tank reactor. Peak hydrogen production rate and
      hydrogen yield of 9.57 L/L-d and 1.10 mol/mol galactoseadded, respectively, were
      obtained at a feed substrate concentration of 30 g/L and an organic loading rate
      of 60 L/L-d. Quantitative polymerase chain reaction analysis showed that the
      variations in the performance resulted primarily from metabolic alterations
      within the metabolism of the established microbial community rather than
      modifications in the population. The results obtained showed that optimal
      substrate concentration is essential for the efficient, continuous production of
      hydrogen from galactose.

PMID- 29337033
TI  - Gliclazide, a KATP channel blocker, inhibits vascular smooth muscle cell
      proliferation through the CaMKKbeta-AMPK pathway.
AB  - Gliclazide, a sulfonylurea that is widely used to treat type II-diabetes,
      specifically blocks KATP channels and recombinant smooth muscle (SUR2B/Kir6.1)
      KATP channels with high potency. Furthermore, it exerts antioxidant properties
      and inhibits tumor cell proliferation. In this study, we investigated the
      inhibitory effect of gliclazide on vascular smooth muscle cell (VSMC)
      proliferation and tried to identify the underlying signaling pathway. We first
      investigated the effect of gliclazide-induced AMP-activated protein kinase (AMPK)
      activation on the proliferation of VSMCs. Gliclazide induced phosphorylation of
      AMPK in a dose- and time-dependent manner and inhibited VSMC proliferation
      following stimulation by platelet-derived growth factor (PDGF). However, KATP
      channel openers and Kir6.1 siRNA prevented gliclazide-mediated inhibition of VSMC
      proliferation. Gliclazide also increased the levels of Ca2+/calmodulin-dependent
      protein kinase kinase beta (CaMKKbeta), an upstream kinase of AMPK. These
      findings suggested that the effects of KATP channels on AMPK activity were
      mediated by the regulation of intracellular Ca2+ levels. Oral administration of
      2mg/kg gliclazide resulted in the activation of CaMKKbeta and AMPK in vivo,
      suggesting that gliclazide suppressed VSMC proliferation via the CaMKKbeta-AMPK
      signaling pathway. Taken together, our observations indicated that gliclazide
      induced AMPK activation may act to prevent diabetes-associated atherosclerosis.

PMID- 29337034
TI  - Establishment of trimester-specific reference range for thyroid hormones during
      pregnancy.
AB  - OBJECTIVE: Physiological gestational changes are associated with alterations in
      thyroid function which require different biochemical interpretation from that of
      non-pregnant women and necessitate established pregnancy-specific reference
      ranges. We aimed to identify the trimester-specific ranges of thyroid markers in
      a healthy population of pregnant Iranian women. METHODS: In this self-sequential
      study, data were extracted from The Tehran Thyroid and Pregnancy Study; a total
      of 314 women were tested during the 1st, 2nd and 3rd trimesters for serum levels
      of thyrotropin (TSH), thyroxine (T4), free thyroxine index (FT4I) and thyroid
      peroxidase antibody (TPOAb). Trimester-specific reference intervals for TSH, T4
      and FT4I and first trimester reference range for TPOAb were estimated. The normal
      and modulus exponential-normal models were fitted by maximum likelihood using
      STATA software. The 2.5th and 97.5th percentiles of thyroid parameters were
      determined and used as reference intervals. RESULTS: Mean+/-SD age of
      participants was 26.8+/-5.2years. Estimated reference intervals for TSH, T4 and
      FT4I in the 1st, 2nd and 3rd trimesters corresponding to the 2.5th and 97.5th
      percentiles were 0.14-6.14, 0.43-4.64, 0.63-3.9MUIU/ml; 78.01-215.19, 93.23
      243.87, 89.61-211.37nmol/L; and 1.73-4.53, 1.96-5.64, 1.72-4.30, respectively.
      Reference interval for TPOAb in the 1st trimester was 1.40-38.02IU/mL. Median of
      TSH was low in the 1st trimester, and gradually increased until 2nd trimester,
      followed by a slight decrease onward. A decreasing trend in TSH levels was
      observed in higher centiles with advancing gestational age. CONCLUSION: This
      study provides trimester-specific reference ranges for some common thyroid
      markers among healthy Iranian women in an iodine sufficient area, to prevent
      biochemical misinterpretations during pregnancy.

PMID- 29337035
TI  - Early Warning Scores do not accurately predict mortality in sepsis: A meta
      analysis and systematic review of the literature.
AB  - OBJECTIVES: Early Warning Scores are used to evaluate patients in many hospital
      settings. It is not clear if these are accurate in predicting mortality in
      sepsis. We performed a systematic review and meta-analysis of multiple studies in
      sepsis. Our aim was to estimate the accuracy of EWS for mortality in this
      setting. METHODS: PubMED, CINAHL, Cochrane, Web of Science and EMBASE were
      searched to October 2016. Studies of adults with sepsis who had EWS calculated
      using any appropriate tool (e.g. NEWS, MEWS) were eligible for inclusion. Study
      quality was assessed using QUADAS-2. Summary estimates were derived using HSROC
      analysis. RESULTS: Six studies (4298 participants) were included. Results suggest
      that EWS cannot be used to predict which patients with sepsis will (positive
      likelihood ratio 1.79, 95% CI 1.53 to 2.11) or will not die (negative likelihood
      ratio 0.59, 95% CI 0.45 to 0.78). Two studies were rated as low risk of bias and
      one as unclear risk of bias on all domains. The other three studies were judged
      at high risk of bias in one domain. CONCLUSION: Early Warning Scores are not
      sufficiently accurate to rule in or rule out mortality in patients with sepsis,
      based on the evidence available, which is generally poor quality.

PMID- 29337036
TI  - Potential of real-time PCR threshold cycle (CT) to predict presence of free toxin
      and clinically relevant C. difficile infection (CDI) in patients with cancer: A
      reply.

PMID- 29337037
TI  - Synthesis of new sarsasapogenin derivatives with antiproliferative and apoptotic
      effects in MCF-7 cells.
AB  - Sarsasapogenin, a kind of mainly effective component of Anemarrhena asphodeloides
      Bunge, possesses good antitumor properties. Two series of new sarsasapogenin
      derivatives were synthesized and evaluated for their cytotoxicities against three
      human cancer cell lines (HepG2, A549, MCF-7) using the MTT assay. The structure
      activity relationship revealed that the N, N-dimethylamino, pyrrolidinyl, and
      imidazolyl substituted at the C26 position could increase the antitumor efficacy
      of the 3-oxo sarsasapogenin series of compounds. Compound 4c with pyrrolidinyl
      substituted at the C26 position exhibited the greatest cytotoxic activity against
      MCF-7 cell line (IC50 = 10.66 MUM), which was 4.3-fold more potent than
      sarsasapogenin. Action mechanism investigations showed that 4c could inhibit the
      colony formation and induce the apoptosis of MCF-7 cells. Further researches
      showed that a decrease in mitochondrial membrane potential and increases in the
      expression level of cleaved-PARP and the ratio of Bax/Bcl-2 were observed in MCF
      7 cells after treatment with 4c, suggesting that the mitochondrial pathway was
      involved in the 4c-mediated apoptosis. These results show that compound 4c may
      serve as a lead for further optimization.

PMID- 29337038
TI  - Back to the future: Epigenetic clock plasticity towards healthy aging.
AB  - Aging is the most important risk factor for major human lifestyle diseases,
      including cancer, neurological and cardiometabolic disorders. Due to the complex
      interplay between genetics, lifestyle and environmental factors, some individuals
      seem to age faster than others, whereas centenarians seem to have a slower aging
      process. Therefore, a biochemical biomarker reflecting the relative biological
      age would be helpful to predict an individual's health status and aging disease
      risk. Although it is already known for years that cumulative epigenetic changes
      occur upon aging, DNA methylation patterns were only recently used to construct
      an epigenetic clock predictor for biological age, which is a measure of how well
      your body functions compared to your chronological age. Moreover, the epigenetic
      DNA methylation clock signature is increasingly applied as a biomarker to
      estimate aging disease susceptibility and mortality risk. Finally, the epigenetic
      clock signature could be used as a lifestyle management tool to monitor healthy
      aging, to evaluate preventive interventions against chronic aging disorders and
      to extend healthy lifespan. Dissecting the mechanism of the epigenetic aging
      clock will yield valuable insights into the aging process and how it can be
      manipulated to improve health span.

PMID- 29337040
TI  - Colonic perforation due to GI histoplasmosis in an immunocompetent host mimicking
      Crohn's disease.

PMID- 29337039
TI  - Patients with small and diminutive proximal hyperplastic polyps have higher rates
      of synchronous advanced neoplasia compared with patients without serrated
      lesions.
AB  - BACKGROUND AND AIMS: The association of proximal small and diminutive
      hyperplastic polyps (HPs) with synchronous advanced neoplasia is not well
      defined. However, sessile serrated polyps (SSPs), even when small, are known to
      portend a risk of synchronous neoplasia. Currently, the U.S. Multi-Society Task
      Force on Colorectal Cancer does not recommend a change in the surveillance
      interval when proximal small HPs are detected. We aimed to compare the rates of
      synchronous advanced neoplasia in a screening colonoscopy cohort of patients with
      small and then diminutive proximal HPs in comparison, first to a cohort absent
      any serrated or proximal HPs and then in comparison with a cohort with small
      proximal SSPs. METHODS: Consecutive screening colonoscopies were recorded between
      2005 and 2010 at an academic medical center. Patients were divided into 3
      mutually exclusive groups. Group 1 consisted of patients with at least 1 HP that
      was proximal to the sigmoid colon, <1 cm in endoscopic size, and up to 3 total
      HPs in number. Group 2 included patients without any proximal HPs or SSPs. Group
      3 consisted of patients with 1 to 2 SSPs, with at least 1 being proximal to the
      sigmoid colon, that were <1 cm in endoscopic size and without dysplasia. Rates of
      synchronous advanced neoplasia in patients with small (<1 cm) and diminutive (<=5
      mm) proximal HPs were compared with the rates for the other 2 groups. RESULTS:
      There were 482 of 2569 patients (18.8%) with a small proximal HP who met the
      criteria for Group 1. The rate of synchronous advanced neoplasia in patients with
      a small proximal HP (61/482, 12.7%) was significantly greater compared with the
      average risk in the non-serrated cohort (Group 2, 133/1878, 7.1%; P < .001).
      There was no significant difference in the rate of synchronous advanced neoplasia
      when the small proximal HP group was subdivided by size (<=5 mm, 51/404, 12.6% vs
      6-9 mm, 10/78, 12.8%; P = 1.00). The rate of synchronous advanced neoplasia in
      patients with diminutive (<=5 mm) proximal HPs (51/404, 12.6%) was not
      significantly different from the rate observed with proximal SSPs of similar size
      (17/113, 15.0%; P = .529). CONCLUSION: Patients with small and diminutive
      proximal HPs tend to harbor higher rates of synchronous advanced neoplasia
      compared with those without any serrated lesions detected on screening
      colonoscopy. Surveillance outcomes for metachronous advanced neoplasia for
      patients with small proximal HPs deserves further study. The synchronous advanced
      neoplasia rate in patients with proximal diminutive HPs is similar to that of
      proximal diminutive SSPs and could have implications in a resect and discard
      strategy.

PMID- 29337041
TI  - Provision of abortion and other reproductive health services among former Midwest
      Access Project trainees.
AB  - OBJECTIVE: The Midwest Access Project (MAP) offers opt-in training to students,
      residents and practicing clinicians in reproductive health care including
      abortion. We surveyed MAP alumni to identify current practice characteristics and
      assess predictors of reproductive health service provision. STUDY DESIGN: We sent
      an online survey to alumni of MAP's Individual Clinical Training program, 2007
      2015 (n=127). The primary outcome was current provision of any abortion service.
      Secondary outcomes included providing specific abortion services and other
      reproductive services. RESULTS: We received responses from 61% of eligible MAP
      alumni (n=77 out of 127). The majority reported a specialty of Family Medicine
      (68%) and current location in the Midwest (52%). Among current residents, fellows
      or clinicians practicing in a field whose scope includes abortion (n=56), 50%
      provide abortion. Most (84%) provide outpatient miscarriage management, and
      nearly all (>=96%) provide pregnancy options counseling and full scope
      contraception. Respondents who received the most advanced training in medication
      abortion as part of their MAP training were more likely to report providing
      abortion in their current practice than those who did not (63% vs. 32%, p=.027),
      as were those who completed more than one MAP rotation compared to those who
      completed one rotation (100% vs. 44%, p=.009). CONCLUSIONS: Half of MAP's alumni
      provide some abortion care. Nearly all provide comprehensive counseling and
      contraceptive services. IMPLICATIONS: Opt-in training is a promising strategy to
      develop providers of comprehensive reproductive health care.

PMID- 29337042
TI  - Endovascular recanalization for nonmalignant obstruction of the inferior vena
      cava.
AB  - OBJECTIVE: The aim of this study was to evaluate outcomes of endovascular
      recanalization of the inferior vena cava (IVC) and iliac veins with long-standing
      chronic venous obstruction caused by nonmalignant disease. METHODS: Medical
      records for 66 patients who underwent endovascular recanalization of the IVC with
      or without iliac veins from January 2001 to December 2014 at our medical center
      were retrospectively reviewed. Primary outcomes included morbidity and mortality;
      secondary outcomes included primary, primary assisted, and secondary patency and
      resolution of symptoms. RESULTS: Forty-five (68%) patients were male; the mean
      age was 43 years (range, 17-83 years). All but one patient had chronic symptoms
      (mean duration, 8 +/- 9 years). Clinical, Etiology, Anatomy, and Pathophysiology
      classes included 3, 4a, 4b, 5, and 6 in 41, 2, 1, 2, and 20 patients,
      respectively. Mean Venous Clinical Severity Score was 12.4 +/- 6.5. Fifty-nine
      patients (89%) had history of deep venous thrombosis, and 13 also had pulmonary
      embolism. Twenty-five patients (38%) had an IVC filter; 20 (30%) had
      thrombophilia. The obstruction involved the infrarenal IVC in 44 patients and
      both the infrarenal and suprarenal IVC in 22 patients. All recanalizations were
      performed under conscious sedation and local anesthesia and involved sequential
      angioplasty and stent placement into the IVC, with or without iliac vein
      stenting. Venous access included bilateral femoral veins and right internal
      jugular vein. Stents used were Wallstents (Boston Scientific, Marlborough, Mass;
      n = 70), Protege stents (ev3, Plymouth, Minn; n = 49), Gianturco (Cook Medical,
      Bloomington, Ind; n = 44), and Luminexx (Bard, Tempe, Ariz; n = 1). Pressure
      gradients were 6.7 +/- 4.0 mm Hg before and 0.9 +/- 1.1 mm Hg after stenting (P <
      .001). Procedural success was 90% and 100% at first and second attempt at
      recanalization, respectively. There was no mortality or clinically significant
      pulmonary embolism. Four patients had five complications: two developed an
      arteriovenous fistula, one patient developed groin hematoma that required open
      evacuation, and one had peri-IVC hematoma and femoral vein thrombosis that
      required repeated angioplasty and stenting; 93% of patients received long-term
      anticoagulation. Follow-up was 42 +/- 36 months. Four patients were lost to
      follow-up. Primary patency, primary assisted patency, and secondary patency at 36
      months were 78%, 87%, and 91%, respectively. Symptoms resolved in 83% of
      patients. On multivariable regression analysis, hypercoagulable state was the
      only predictor of reocclusion of the recanalized veins. CONCLUSIONS: Endovascular
      recanalization for nonmalignant symptomatic IVC and associated iliofemoral venous
      obstruction with balloon angioplasty and self-expanding stents is technically
      challenging; however, it is safe and durable. In our retrospective study,
      estimated patency rates at 36 months were >85%, and clinical outcomes were
      excellent. Venous stenting should be attempted for chronic nonmalignant IVC and
      associated iliac or iliofemoral venous obstructions before open surgical
      reconstruction is contemplated.

PMID- 29337043
TI  - Membrane-permeable Rab27A is a regulator of the acrosome reaction: Role of
      geranylgeranylation and guanine nucleotides.
AB  - The acrosome reaction is the regulated exocytosis of mammalian sperm's single
      secretory granule, essential for fertilization. It relies on small GTPases, the
      cAMP binding protein Epac, and the SNARE complex, among other components. Here,
      we describe a novel tool to investigate Rab27-related signaling pathways: a
      hybrid recombinant protein consisting of human Rab27A fused to TAT, a cell
      penetrating peptide. With this tool, we aimed to unravel the connection between
      Rab3, Rab27 and Rap1 in sperm exocytosis and to deepen our understanding about
      how isoprenylation and guanine nucleotides influence the behaviour of Rab27 in
      exocytosis. Our results show that TAT-Rab27A-GTP-gamma-S permeated into live
      sperm and triggered acrosomal exocytosis per se when geraylgeranylated but
      inhibited it when not lipid-modified. Likewise, an impermeant version of Rab27A
      elicited exocytosis in streptolysin O-permeabilized - but not in non
      permeabilized - cells when geranylgeranylated and active. When GDP-beta-S
      substituted for GTP-gamma-S, isoprenylated TAT-Rab27A inhibited the acrosome
      reaction triggered by progesterone and an Epac-selective cAMP analogue, whereas
      the non-isoprenylated protein did not. Geranylgeranylated TAT-Rab27A-GTP-gamma-S
      promoted the exchange of GDP for GTP on Rab3 and Rap1 detected by far
      immunofluorescence with Rab3-GTP and Rap1-GTP binding cassettes. In contrast, TAT
      Rab27A lacking isoprenylation or loaded with GDP-beta-S prevented the activation
      of Rab3 and Rap1 elicited by progesterone. Challenging streptolysin O
      permeabilized human sperm with calcium increased the population of sperm with
      Rap1-GTP, Rab3-GTP and Rab27-GTP in the acrosomal region; pretreatment with anti
      Rab27 antibodies prevented the activation of all three. The novel findings
      reported here include: the description of membrane permeant TAT-Rab27A as a
      trustworthy tool to unveil the regulation of the human sperm acrosome reaction by
      Rab27 under physiological conditions; that the activation of endogenous Rab27 is
      required for that of Rab3 and Rap1; and the connection between Epac and Rab27 and
      between Rab27 and the configuration of the SNARE complex. Moreover, we present
      direct evidence that Rab27A's lipid modification, and activation/inactivation
      status correlate with its stimulatory or inhibitory roles in exocytosis.

PMID- 29337044
TI  - Lysophosphatidic acid regulates the motility of MCF10CA1a breast cancer cell
      sheets via two opposing signaling pathways.
AB  - Aberrant cell migration leads to the dispersal of malignant cells. The ubiquitous
      lipid mediator lysophosphatidic acid (LPA) modulates cell migration and is
      implicated in tumor progression. Yet, the signaling cascades that regulate LPA's
      effect on cell motility remain unclear. Using time-lapse imaging and quantitative
      analyses, we studied the role of signaling cascades that act downstream of LPA on
      the motility of MCF10CA1a breast cancer cells. We found that LPA alters cell
      motility via two major signaling pathways. The Rho/ROCK signaling cascade is the
      predominant pathway that increases E-Cadherin containing cell-cell adhesions and
      cortical arrangement of actomyosin to promote slow, directional, spatially
      coherent and temporally consistent movement. In contrast, Galphai/o- and
      Galphaq/11-dependent signaling cascades lessen directionality and support the
      independent movement of cells. The net effect of LPA on breast cancer cell
      migration therefore results from the integrated signaling activity of the
      Rho/ROCK and Galphai/o- and Galphaq/11-dependent pathways, thus allowing for a
      dynamic migratory response to changes in the cellular or microenvironmental
      context.

PMID- 29337045
TI  - Increased dendritic length in CA1 and CA3 hippocampal neurons during the
      metestrus phase in Wistar rats.
AB  - Studies have shown that changes in ovarian hormone concentrations promote natural
      fluctuations in the density of dendritic spines of hippocampal neurons in female
      Sprague-Dawley rats, without changes in dendritic length, throughout the estrous
      cycle. However, it is still unknown whether these fluctuations are present in
      other rat strains. Due to our interest in Wistar rats, the objective of the
      present study was to determine if there is natural dendritic remodeling in the
      female Wistar rat throughout the estrous cycle. This study analyzed the dendritic
      arborization of pyramidal neurons CA1 and CA3 of the dorsal hippocampus in each
      phase of the estrous cycle. We used the Golgi-Cox staining method and Sholl
      analysis to evaluate the dendritic length and density of dendritic spines. Our
      results showed that the dendritic length of the basilar and apical trees of CA1
      neurons was longer in the metestrus phase. In CA3 neurons, only the apical
      dendritic trees showed longer dendritic length during metestrus. There was no
      variation in the density of dendritic spines in relation to any of the phases of
      the estrous cycle. Taken together, these results indicated that pyramidal neurons
      of the CA1 and CA3 regions of the dorsal hippocampus in the Wistar rat exhibited
      changes in dendritic length in the metestrus phase of the estrous cycle.
      Together, these data are important when considering the use of these organisms in
      behavioral studies.

PMID- 29337046
TI  - The impact of fast track protocols in upper gastrointestinal surgery: A meta
      analysis of observational studies.
AB  - BACKGROUND: Fast track surgery has been implemented in colorectal procedures
      during the last decade and is accompanied by significant improvement in patient
      outcomes during the early postoperative period. However, to date, its adoption in
      upper gastrointestinal surgery remains a matter of debate. In this context, we
      aimed to summarize the existing evidence in the international literature.
      MATERIALS AND METHODS: We searched Medline, Scopus, ClinicalTrials.gov and
      Cochrane Central Register databases for published randomized controlled trials.
      The meta-analysis was performed with the RevMan 5.3.5 software. MAIN FINDINGS:
      Thirty studies were finally included in the present meta-analysis. The post
      operative morbidity was not influenced by the implementation of fast track
      surgery (FTS) (OR 0.84, 95% CI 0.64-1.09). However, in cases treated with
      laparoscopic surgery fast track surgery seemed to reduce morbidity by 50% (p =
      .006). The overall mortality of patients was low in the majority of included
      studies and was not influenced by fast track surgery (OR 1.12, 95% CI 0.50-2.52).
      The duration of postoperative hospitalization was significantly reduced with the
      adoption of FTS (MD -2.24, 95% CI -2.63 to -1.85 days). Concurrently, the overall
      cost was significantly reduced in cases treated with FTS (MD -982.30, 95% CI 
      1367.68 to -596.91 U.S dollars). CONCLUSION: According to the findings of our
      meta-analysis suggest that FTS seems to be safe in patients undergoing upper
      gastrointestinal surgery and reduce both the days of postoperative
      hospitalization and the overall cost. This observation should be taken into
      account in future recommendations to enhance the implementation of FTS protocols
      in current clinical practice.

PMID- 29337047
TI  - Imaging flow cytometry: A method for examining dynamic native FOXO1 localization
      in human lymphocytes.
AB  - While flow cytometry can reliably assess surface and intracellular marker
      expression within small cell populations, it does not provide any information on
      protein localization. Several key transcription factors (TF) downstream of
      lymphocyte surface receptors are regulated by nuclear versus cytoplasmic
      localization, and one such TF is Forkhead box O1 (FOXO1). FOXO1 integrates
      antigen-binding, co-receptor activation and metabolic signals in lymphocytes,
      leading to proliferation and differentiation. Importantly, the nuclear or
      cytoplasmic localization of FOXO1 is key for gene expression leading to different
      lymphocyte phenotypes. In effector lymphocytes (Teff), for example, lymphocyte
      receptor (TCR) signaling leads to an Akt-dependent phosphorylation of FOXO1.
      Phosphorylated FOXO1 is excluded from the nucleus, promoting proliferation and
      effector functions. In contrast, nuclear retention of FOXO1 is essential for
      early and late development of T and B cells and for the thymic development and
      stability of regulatory T cells. Given the critical role of FOXO1 localization as
      an indicator and determinant of function, quantification of FOXO1 cellular
      localization in human lymphocytes can help determine immune cell activation and
      activity in experimental and clinical scenarios. The standard method used to
      determine subcellular protein localization is the analysis of nuclear and
      cytoplasmic protein extracts by Western blotting (WB). However, available
      techniques, such as WB, are limited by a requirement for a large number of cells
      and inability to determine FOXO1 localization in individual cells or sub
      populations. In contrast, a standardized method using an imaging flow cytometer
      (IFC) such as the Amnis ImagestreamX Mark II, would provide both qualitative, per
      cell localization information, as well as quantitative data on gated sub
      populations. To this end, we report the development and optimization of an IFC
      protocol to examine native FOXO1 localization in human lymphocytes. A human CD4+
      lymphocyte line, HuT102, as well as primary human T cells, were assessed for
      dynamic FOXO1 localization after treatment with a lymphocyte receptor signaling
      mimic (PMA/Ionomycin). IFC nuclear translocation analysis permitted us to
      precisely quantify the alterations over time in nuclear and cytoplasmic
      localization of native FOXO1 on a per cell basis, including within specific, user
      defined sub-populations of cells. For human lymphocytes, using IFC to assess and
      quantify dynamic FOXO1 localization allows the user to simultaneously study
      multiple lymphocyte subpopulations as well as to delineate differing effects of
      dynamic FOXO1 localization that may be lost when other available methods are
      used.

PMID- 29337048
TI  - Pathologic Findings of Symptomatic Carotid Artery Stenosis Several Decades after
      Radiation Therapy: A Case Report.
AB  - Improved long-term survival of malignancy has drawn increased attention to late
      cerebrovascular toxicity after neck radiotherapy. Recently, neck radiotherapy has
      been found as a significant risk factor of carotid artery stenosis and ischemic
      stroke; however, long-term adverse effects of radiation in large arteries remain
      unknown. Here, we described an autopsied case with recurrent ischemic stroke
      associated with ipsilateral carotid artery stenosis several decades after neck
      radiation therapy. Pathologically, there were intima-media fibrosis, endothelial
      cell loss, and decreased expression of thrombomodulin in irradiated carotid
      artery stenosis. Our findings support the hypothesis that long-term radiation
      induced vascular injury in large arteries is morphologically different from
      atherosclerotic change. Furthermore, endothelial cell injury may promote fibrin
      thrombus formation through decreased expression of thrombomodulin, which may
      cause ischemic stroke associated with radiation-induced carotid artery stenosis.

PMID- 29337049
TI  - Sphingosine-1-Phosphate Receptor 1 Activation Enhances Leptomeningeal Collateral
      Development and Improves Outcome after Stroke in Mice.
AB  - BACKGROUND: Development of collateral circulation after acute ischemic stroke is
      triggered by shear stress that occurs in pre-existing arterioles. Recently,
      sphingosine-1-phosphate receptor 1 (S1P1) on endothelial cells was reported to
      sense shear stress and transduce its signaling pathways. METHODS: BALB/c mice (n
      = 118) were subjected to permanent middle cerebral artery occlusion (pMCAO) or
      sham operation. We investigated the effect of an S1P1-selective agonist SEW2871
      on leptomeningeal collateral arteries and neurological outcome after pMCAO.
      RESULTS: Immunohistochemistry showed that without treatment, the expression of
      S1P1 on endothelial cells of leptomeningeal arteries and capillaries increased
      early after pMCAO, peaking at 6 hours, whereas a significant increase in the
      expression of S1P1 in neurons was seen from 24 hours later. After intraperitoneal
      administration of SEW2871 for 7 days after pMCAO, the number of leptomeningeal
      collateral arteries was significantly increased, cerebral blood flow improved,
      infarct volume was decreased, and neurological outcome improved compared with the
      controls. Significantly increased phosphorylation of endothelial nitric oxide
      synthase (eNOS) as early as 6 hours after pMCAO and higher expression of tight
      junction proteins at postoperative day 3 were observed with SEW2871 treatment as
      assessed by Western blot. Daily administration of SEW2871 also increased
      capillary density in peri-infarct regions and promoted monocyte/macrophage
      mobilization to the surface of ischemic cortex at 7 days after pMCAO.
      CONCLUSIONS: An S1P1-selective agonist enhanced leptomeningeal collateral
      circulation via eNOS phosphorylation and promoted postischemic angiogenesis with
      reinforced blood-brain barrier integrity in a mouse model of acute ischemic
      stroke, leading to smaller infarct volume and better neurological outcome.

PMID- 29337050
TI  - Impairments in social novelty recognition and spatial memory in mice with
      conditional deletion of Scn1a in parvalbumin-expressing cells.
AB  - Loss of function mutations in the SCN1A gene, which encodes the voltage-gated
      sodium channel Nav1.1, have been described in the majority of Dravet syndrome
      patients presenting with epileptic seizures, hyperactivity, autistic traits, and
      cognitive decline. We previously reported predominant Nav1.1 expression in
      parvalbumin-expressing (PV+) inhibitory neurons in juvenile mouse brain and
      observed epileptic seizures in mice with selective deletion of Scn1a in PV+ cells
      mediated by PV-Cre transgene expression (Scn1afl/+/PV-Cre-TG). Here we
      investigate the behavior of Scn1afl/+/PV-Cre-TG mice using a comprehensive
      battery of behavioral tests. We observed that Scn1afl/+/PV-Cre-TG mice display
      hyperactive behavior, impaired social novelty recognition, and altered spatial
      memory. We also generated Scn1afl/+/SST-Cre-KI mice with a selective Scn1a
      deletion in somatostatin-expressing (SST+) inhibitory neurons using an SST-IRES
      Cre knock-in driver line. We observed that Scn1afl/+/SST-Cre-KI mice display no
      spontaneous convulsive seizures and that Scn1afl/+/SST-Cre-KI mice have a lowered
      threshold temperature for hyperthermia-induced seizures, although their threshold
      values are much higher than those of Scn1afl/+/PV-Cre-TG mice. We finally show
      that Scn1afl/+/SST-Cre-KI mice exhibited no noticeable behavioral abnormalities.
      These observations suggest that impaired Nav1.1 function in PV+ interneurons is
      critically involved in the pathogenesis of hyperactivity, autistic traits, and
      cognitive decline, as well as epileptic seizures, in Dravet syndrome.

PMID- 29337051
TI  - FERMT2 links cortical actin structures, plasma membrane tension and focal
      adhesion function to stabilize podocyte morphology.
AB  - Simplification and retraction of podocyte protrusions, generally termed as foot
      process effacement, is a uniform pathological pattern observed in the majority of
      glomerular disease, including focal segmental glomerulosclerosis. However, it is
      still incompletely understood how the interaction of cortical actin structures,
      actomyosin contractility and focal adhesions, is being orchestrated to control
      foot process morphology in health and disease. By uncovering the functional role
      of fermitin family member 2 (FERMT2 or kindlin-2) in podocytes, we provide now
      evidence, how cell-extracellular matrix (ECM) interactions modulate membrane
      tension and actomyosin contractility. A genetic modeling approach was applied by
      deleting FERMT2 in a set of in vivo systems as well as in CRISPR/Cas9 modified
      human podocytes. Loss of FERMT2 results in altered cortical actin composition,
      cell cortex destabilization associated with plasma membrane blebbing and a
      remodeling of focal adhesions. We further show that FERMT2 knockout podocytes
      have high levels of RhoA activation and concomitantly increased actomyosin
      contractility. Inhibition of actomyosin tension reverses the membrane blebbing
      phenotype. Thus, our findings establish a direct link between cell-matrix
      adhesions, cortical actin structures and plasma membrane tension allowing to
      better explain cell morphological changes in foot process effacement.

PMID- 29337052
TI  - Sweet, yet underappreciated: Proteoglycans and extracellular matrix remodeling in
      heart disease.
AB  - Extracellular matrix remodeling is extensive in several heart diseases and
      hampers cardiac filling, often leading to heart failure. Proteoglycans have over
      the last two decades emerged as molecules with important roles in matrix
      remodeling and fibrosis in the heart. Here we discuss and review current
      literature on proteoglycans that have been studied in cardiac remodeling. The
      small leucine rich proteoglycans (SLRPs) are located within the extracellular
      matrix and are organizers of the matrix structure. Membrane-bound proteoglycans,
      such as syndecans and glypicans, act as receptors and direct cardiac fibroblast
      signaling. Recent studies indicate that proteoglycans are promising as diagnostic
      biomarkers for cardiac fibrosis, and that they may provide new therapeutic
      strategies for cardiac disease.

PMID- 29337053
TI  - Oral ingestion of plasmalogens can attenuate the LPS-induced memory loss and
      microglial activation.
AB  - Plasmalogens (Pls) are the special phospholipids which were reported to be
      reduced in brain and blood samples of Alzheimer's disease (AD) patients,
      suggested a possibility that an oral ingestion of Pls may prevent the disease
      progression. Interestingly, the clinical study showed that the daily oral
      ingestion of Pls among the mild AD patients improved cognition. However, it is
      unknown of whether the oral ingestion of Pls inhibits the AD like changes in
      brain e.g., glial activation and accumulation of amyloid beta (Abeta) proteins.
      To elucidate the beneficial effects of the Pls oral ingestion, we have used the
      chronic lipopolysaccharide (LPS) injection model mice where the glial activation
      and Abeta accumulation were well reported. In the present study, we have found
      that the Pls drinking at the doses of 0.1 MUg/ml and 10 MUg/ml for 3 months
      attenuated the glial activation and accumulation of amyloid beta (Abeta) proteins
      in the murine brain. Interestingly, the LPS injection reduced the hippocampal
      dependent memory in the control mice but the groups of Pls drinking mice showed a
      better performance in the memory test, suggesting that oral intake of Pls can
      inhibit LPS-mediated memory loss associated with a reduction of glial activation
      and Abeta accumulation in the brain. We, therefore, suggest that the oral
      ingestion of Pls among the AD patients may also inhibit the glial activation
      resulting in the improvement of cognition.

PMID- 29337054
TI  - Deficiency of primary cilia in kidney epithelial cells induces epithelial to
      mesenchymal transition.
AB  - Primary cilium is a microtubule-based non-motile organelle that plays critical
      roles in kidney pathophysiology. Our previous studies revealed that the lengths
      of primary cilia decreased upon renal ischemia/reperfusion injury and oxidative
      stress, and restored with recovery. Here, we tested the hypothesis that lack of
      primary cilium causes epithelial to mesenchymal transition (EMT) of kidney tubule
      cells. We investigated the alteration of length of primary cilia in TGF-beta
      induced EMT via visualization of primary cilia by fluorescence staining against
      acetylated alpha-tubulin. EMT was determined by measuring mesenchymal protein
      expression using quantitative PCR and indirect fluorescence staining. As a
      result, TGF-beta treatment decreased ciliary length along with EMT. To test
      whether defect of primary cilia trigger onset of EMT, cilia formation was
      disturbed by knock down of ciliary protein using siRNA along with/without TGF
      beta treatment. Knock down of Arl13b and Ift20 reduced cilia elongation and
      increased expression of EMT markers such as fibronectin, alpha-SMA, and collagen
      III. TGF-beta-induced EMT was greater as well in Arl13b and Ift20-knock down
      cells compared to control cells. Taken together, deficiency of primary cilia
      trigger EMT and exacerbates it under pro-fibrotic signals.

PMID- 29337055
TI  - A novel circular RNA, hsa_circ_0046701, promotes carcinogenesis by increasing the
      expression of miR-142-3p target ITGB8 in glioma.
AB  - In the present study, we identified a novel circular RNA (circRNA),
      hsa_circ_0046701, in glioma cells. We measured the expression of hsa_circ_0046701
      using qRT-PCR in glioma tissues and cell lines, and explored its functions using
      3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, colony formation,
      and Transwell assays. Luciferase reporter assays were performed to validate the
      correlation between microRNA miR-142-3p and hsa_circ_0046701 or integrin subunit
      beta 8 (ITGB8). The results showed that hsa_circ_0046701 was significantly
      upregulated in glioma tissues and cell lines, and knockdown of hsa_circ_0046701
      inhibited cell proliferation and invasion. Luciferase reporter assays indicated
      that hsa_circ_0046701 functions as a sponge for miR-142-3p and regulates the
      expression of ITGB8. Subsequently, functional assays revealed that silencing of
      hsa_circ_0046701 could upregulate miR-142-3p, resulting in downregulation of
      ITGB8. The results demonstrated that the hsa_circ_0046701/miR-142-3p/ITGB8 axis
      might play critical regulatory roles in the pathogenesis and development of
      glioma.

PMID- 29337056
TI  - Comparison of EMT mediated tyrosine kinase inhibitor resistance in NSCLC.
AB  - In the United States, lung cancer is the second most common cancer in men and
      women. In 2017, 222,500 new cases and 155,870 deaths from lung cancer are
      estimated to have occurred. A tyrosine kinase receptor, epidermal growth factor
      receptor (EGFR), is over expressed or mutated in non-small cell lung cancer
      (NSCLC) resulting in increased cell proliferation and survival. Tyrosine kinase
      inhibitors (TKIs) are currently being used as therapy for NSCLC patients,
      however, they have limited efficacy in NSCLC patients due to acquisition of
      resistance. This study investigates the role of epithelial-mesenchymal transition
      (EMT) in the development of resistance against TKIs in NSCLC. Currently, the role
      of p120-catenin, Kaiso factor and PRMT-1 in reversal of EMT in T790M mutated and
      TKI-resistant NSCLC cells is a new line of study. In this investigation we found
      upregulation of cytoplasmic p120-catenin, which was co-localized with Kaiso
      factor. In the nucleus, binding of p120-catenin to Kaiso factor initiates
      transcription by activating EMT-transcription factors such as Snail, Slug, Twist,
      and ZEB1. PRMT-1 was also found to be upregulated, which induces methylation of
      Twist and repression of E-cadherin activity, thus promoting EMT. We confirmed
      that TKI-resistant cells have mesenchymal cell type characteristics based on
      their cell morphology and gene or protein expression of EMT related proteins. EMT
      proteins, Vimentin and N-cadherin, displayed increased expression, whereas E
      cadherin expression was downregulated. Finally, we found that the knockdown of
      p120-catenin and PRMT-1 by siRNA or use of a PRMT-1 inhibitor Furamidine
      increased Erlotinib sensitivity and could reverse EMT to overcome TKI resistance.

PMID- 29337057
TI  - Heterogeneity of autophagic status in pancreatic beta cells under metabolic
      stress.
AB  - Autophagy in beta cells has been demonstrated to play a pivotal role in cellular
      homeostasis and the progression of glucose intolerance. Although autophagic
      activity is affected by metabolic stress both in vivo and in vitro, it remains
      unclear as to what extent the autophagic status in each beta cell is different
      from its neighboring cells. To address this question, GFP-LC3 reporter mice,
      which can visualize the autophagic status of each beta cell as green-fluorescent
      puncta, were crossed with obese diabetic db/db mice. Imaging of green-fluorescent
      puncta in the islets of GFP-LC3 mice revealed that beta cells are a heterogeneous
      population, as the density of GFP-LC3 puncta in each cell was variable.
      Furthermore, the variability was greater in GFP-LC3; db/db mice than in non
      diabetic GFP-LC3; db/+ mice. Furthermore, when GFP-LC3 mice were treated with a
      low dose of S961, which antagonizes insulin signaling without inducing overt
      hyperglycemia, the number of beta cells with a high density of GFP puncta was
      increased, suggesting that insulin resistance affects autophagic status
      independently of glucose profiles. These results suggest that pancreatic beta
      cells under metabolic stress are heterogeneous regarding their autophagic status,
      which provides insights into the cellular dynamics of each beta cell rather than
      the whole beta-cell population.

PMID- 29337058
TI  - EHMT2 is a metastasis regulator in breast cancer.
AB  - Various modes of epigenetic regulation of breast cancer proliferation and
      metastasis have been investigated, but epigenetic mechanisms involved in breast
      cancer metastasis remain elusive. Thus, in this study, EHMT2 (a histone
      methyltransferase) was determined to be significantly overexpressed in breast
      cancer tissues and in Oncomine data. In addition, knockdown of EHMT2 reduced cell
      migration/invasion and regulated the expression of EMT-related markers (E
      cadherin, Claudin 1, and Vimentin). Furthermore, treatment with BIX-01294, a
      specific inhibitor of EHMT2, affected migration/invasion in MDA-MB-231 cells.
      Therefore, our findings demonstrate functions of EHMT2 in breast cancer
      metastasis and suggest that targeting EHMT2 may be an effective therapeutic
      strategy for preventing breast cancer metastasis.

PMID- 29337059
TI  - FPPS mediates TGF-beta1-induced non-small cell lung cancer cell invasion and the
      EMT process via the RhoA/Rock1 pathway.
AB  - Farnesyl pyrophosphate synthase (FPPS), a key enzyme in the mevalonate pathway,
      was recently shown to play a role in cancer progression. However, its role in non
      small cell lung cancer (NSCLC) metastasis and the underlying mechanism remain
      unclear. In this study, FPPS expression was significantly correlated with TNM
      stage, and metastasis. Inhibition or knockdown of FPPS blocked TGF-beta1-induced
      cell invasion and epithelial-to-mesenchymal transition (EMT) process. FPPS
      expression of FPPS was induced by TGF-beta1 and FPPS promoted cell invasion and
      EMT via the RhoA/Rock1 pathway. In conclusion, FPPS mediates TGF-beta1-induced
      lung cancer cell invasion and EMT via the RhoA/Rock1 pathway. These findings
      suggest new treatment strategies to reduce mortality associated with metastasis
      in patients with NSCLC.

PMID- 29337060
TI  - Amelogenin X impacts age-dependent increase of frequency and number in labial
      incisor grooves in C57BL/6.
AB  - Labial grooves in maxillary incisors have been reported in several wild-type
      rodent species. Previous studies have reported age-dependent labial grooves occur
      in moderate prevalence in C57BL/6 mice; however, very little is known about the
      occurrence of such grooves. In the present study, we observed age-dependent
      groove formation in C57BL/6 mice up to 26 months after birth and found that not
      only the frequency of the appearance of incisor grooves but also the number of
      grooves increased in an age-dependent manner. We examined the molecular
      mechanisms of age-dependent groove formation by performing DNA microarray
      analysis of the incisors of 12-month-old (12M) and 24-month-old (24M) mice.
      Amelx, encoding the major enamel matrix protein AMELOGENIN, was identified as a
      12M-specific gene. Comparing with wild-type mice, the maxillary incisors of Amelx
      /- mutants indicated the increase of the frequency and number of labial grooves.
      These findings suggested that the Amelx gene impacts the age-dependent appearance
      of the labial incisor groove in C57BL/6 mice.

PMID- 29337061
TI  - Metabolic reprogramming in keloid fibroblasts: Aerobic glycolysis and a novel
      therapeutic strategy.
AB  - Keloids, tumor-like fibroproliferative cutaneous lesions, were reported in
      metabolic disturbance. However, the metabolic character remains unclear. The
      purpose of this study is to determine if glycolytic reprogramming is important
      for the pathogenesis of keloids and to assess the inhibition potential of
      glycolysis in keloid treatment. An intracellular metabolic profile assay was used
      to compare metabolic phenotypes between normal skin fibroblasts and keloid
      fibroblasts (NFs and KFs). Our data indicated that KFs underwent reprogramming of
      their metabolic phonotype from oxidative phosphorylation to aerobic glycolysis
      (Warburg effect) with augmented glycolysis and glycolytic capacity. Both gene and
      protein assays showed that the expression of glycolytic enzymes was upregulated
      in KFs compared to NFs. Our data showed higher glucose influx and lactate
      production in KFs compared to NFs. Furthermore, the proliferation of KFs was
      suppressed in a dose-dependent and time-dependent manner after inhibition of
      glycolysis with 2-deoxy-glucose (2-DG). Taken together, these findings suggested
      that keloids underwent a reprogrammed metabolic phenotype of aerobic glycolysis.
      This was essential for keloid hyperplasia, and glycolytic inhibitors might
      provide a potential treatment for keloids.

PMID- 29337062
TI  - Anti-inflammatory and proresolution activities of bergapten isolated from the
      roots of Ficus hirta in an in vivo zebrafish model.
AB  - Bergapten (5-methoxypsoralen), a coumarin-derivate compound isolated from Ficus
      hirta roots, was evaluated for its anti-inflammatory and proresolution activities
      in a tail-cutting-induced zebrafish larvae model. Bergapten was evaluated using a
      caudal fin-wounded transgenic zebrafish line "Tg(corola: eGFP)" to visualize the
      effects of the recruitment and clearance of neutrophils and macrophages at the
      injury site. We found that bergapten significantly suppressed the recruitment of
      neutrophils and macrophages toward the injury site, as well as promoted the
      clearance of neutrophils and macrophages from the wound site. We also
      investigated the reactive oxygen species (ROS) and nitric oxide (NO) level of
      bergapten in a tail-cutting-induced inflammation zebrafish model. The Results
      revealed that bergapten effectively inhibited the tail-cutting-induced production
      of ROS and NO in zebrafish larvae. This study reported for the first time the
      potential anti-inflammatory and proresolution activities of bergapten in an in
      vivo zebrafish model, suggesting that bergapten may be a potential candidate for
      inflammation therapy.

PMID- 29337063
TI  - BMI1 activates WNT signaling in colon cancer by negatively regulating the WNT
      antagonist IDAX.
AB  - Aberrant activation of Wnt signaling plays a critical role in the development of
      colon cancer. BMI, a component of the polycomb repressive complex (PRC1), is
      upregulated in various types of cancer and contributes to epigenetic silencing of
      tumor suppressors. In this study, we showed that BMI1 is upregulated in colon
      cancer tissues and cell lines. Overexpression of BMI1 in primary epithelial colon
      cells promotes cellular growth and activates WNT pathway, while BMI1 silencing in
      colon cancer cells represses these effects. We also found that BMI1 binds to the
      promoter of IDAX, a Wnt antagonist, and decreases its transcription. Expression
      of IDAX is downregulated in colon cancer tissues and cell lines and negatively
      correlated with BMI1 in colon cancer tissues. Furthermore, Silencing of IDAX
      counteracts the effects of BMI1 suppression, while its overexpression reverses
      oncogenic effects of BMI1. Together, these findings indicate that BMI1-mediated
      IDAX epigenetic suppression is crucial for enhancement of colon carcinogenesis,
      suggesting that BMI1?IDAX axis as a potential novel diagnostic and therapeutic
      target of colon cancer.

PMID- 29337064
TI  - Cloning and functional characterization of a p-coumaroyl quinate/shikimate 3'
      hydroxylase from potato (Solanum tuberosum).
AB  - Chlorogenic acid (CGA) plays an important role in protecting plants against
      pathogens and promoting human health. Although CGA accumulates to high levels in
      potato tubers, the key enzyme p-coumaroyl quinate/shikimate 3'-hydroxylase (C3'H)
      for CGA biosynthesis has not been isolated and functionally characterized in
      potato. In this work, we cloned StC3'H from potato and showed that it catalyzed
      the formation of caffeoylshikimate and CGA (caffeoylquinate) from p-coumaroyl
      shikimate and p-coumaroyl quinate, respectively, but was inactive towards p
      coumaric acid in in vitro enzyme assays. When the expression of StC3'H proteins
      was blocked through antisense (AS) inhibition under the control of a tuber
      specific patatin promoter, moderate changes in tuber yield as well as phenolic
      metabolites in the core tuber tissue were observed for several AS lines. On the
      other hand, the AS and control potato lines exhibited similar responses to a
      bacterial pathogen Pectobacterium carotovorum. These results suggest that StC3'H
      is implicated in phenolic metabolism in potato. They also suggest that CGA
      accumulation in the core tissue of potato tubers is an intricately controlled
      process and that additional C3'H activity may also be involved in CGA
      biosynthesis in potato.

PMID- 29337065
TI  - Downregulated circular RNA hsa_circ_0001649 regulates proliferation, migration
      and invasion in cholangiocarcinoma cells.
AB  - Cholangiocarcinoma (CCA) is one of the most aggressive malignancies with
      increasing worldwide incidence and is characterized by unfavorable prognosis due
      to its early invasive characteristics and poor response to chemotherapy or
      radiotherapy. Accumulating evidence has indicated that aberrantly expressed
      circular RNAs (circRNAs) are involved in cancer development and progression.
      However, their clinical values and biological roles in CCA remain unclear.
      Hsa_circ_0001649, a novel cancer-related circRNA, has been previously reported to
      be downregulated in hepatocellular carcinoma and gastric cancer. In the present
      study, qRT-PCR was carried out to measure the expression of hsa_circ_0001649 in
      CCA tissue samples and cell lines, and the correlation between hsa_circ_0001649
      expression and clinicopathologic features was analyzed. The biological functions
      of hsa_circ_0001649 in CCA cells were evaluated both in vitro and in vivo. As a
      result, hsa_circ_0001649 was aberrantly downregulated in CCA tissues and cells,
      and this downregulation was associated with tumor size and differentiation grade
      in CCA. In addition, hsa_circ_0001649 overexpression caused tumor suppressive
      effects via inhibiting cell proliferation, migration and invasion; inducing cell
      apoptosis in KMBC and Huh-28 cells. On the contrary, silencing of
      hsa_circ_0001649 caused the opposite phenotypes. Furthermore, tumor xenograft
      study confirmed the in vitro results. Collectively, our findings suggest that
      hsa_circ_0001649 might be a rational CCA-related therapeutic target.

PMID- 29337066
TI  - Listeria monocytogenes endocarditis: case report, review of the literature, and
      laboratory evaluation of potential novel antibiotic synergies.
AB  - Endocarditis is a rare but serious manifestation of Listeria monocytogenes (LM).
      However, the optimal treatment strategy for LM endocarditis has yet to be
      established. Current antibiotic strategies for listeriosis include penicillin G
      or ampicillin (AMP) monotherapy, or AMP + gentamicin combination therapy which is
      often favored for endocarditis. The primary objective of our investigation was to
      assess the utility of AMP + ceftriaxone (CRO) and AMP + daptomycin (DAP) against
      LM, modeling less nephrotoxic antibiotic combinations traditionally used to
      manage resistant enterococcal endocarditis. Here we report a case of LM
      endocarditis, review the world literature, and evaluate alternative treatment
      strategies for listeriosis utilizing in vitro and ex vivo studies. The
      combination of AMP + CRO and AMP + DAP were each noted to have synergistic
      activity against a LM endocarditis isolate. Additionally, co-incubation of the
      isolate with sub-lethal concentrations of antibiotics (AMP, CRO, DAP, AMP + CRO
      or AMP + DAP) sensitized the bacterium to whole blood killing while pretreatment
      with CRO and DAP (at 1/4 MIC) sensitized the bacterium to neutrophil killing.
      However, these effects did not reflect potentiation of antibiotic activity to
      human cathelicidin peptide LL-37, which is abundant in neutrophils and highly
      active against LM. Interestingly, AMP pretreatment of the LM endocarditis isolate
      resulted in increased DAP binding to the bacterium when assessed by fluorescence
      microscopy. These in vitro and ex vivo studies suggest further investigation of
      combination therapy using AMP + CRO or AMP + DAP as an alternative treatment for
      LM infection is warranted.

PMID- 29337067
TI  - The impact of growth factors on human induced pluripotent stem cells
      differentiation into cardiomyocytes.
AB  - : Human induced pluripotent stem cells (hiPSCs) act as a promising therapeutic
      alternative for cardiovascular diseases. They yield a large number of functional
      cardiomyocytes (CMs) from autologous cell sources without ethical or
      immunological problems. However, significant limitations still remain in terms of
      line-to-line variability in CM yield and reproducibility. AIM: To efficiently
      enhance NP0040 hiPSCs differentiation into CMs. MAIN METHODS: Following a
      standard cardiac differentiation protocol using small molecules targeting the
      canonical Wnt signaling, growth factors (BMP4 and FGF2) and ascorbic acid were
      added further in order to increase the cardiac differentiation efficiency. All
      cultures were conducted in serum-free, feeder-free monolayer system followed by
      lactate purification. KEY FINDINGS: Using NP0040 hiPSCs, the CM yield resulting
      from modulation of the Wnt signaling pathway alone was inefficient compared to
      previous studies while the addition of BMP4, FGF2 and ascorbic acid resulted in
      enhanced cardiac differentiation outcome. The later resulted in a high yield (up
      to 92%) of cardiac troponin-T (cTnT) + CMs contracting spontaneously as organized
      sheets in 15 independent experiments. They were validated structurally and
      functionally using immunofluorescent staining for sarcomeric alpha-actinin, cTnT,
      MLC2v and Connexin 43. Reverse-transcriptase PCR revealed cardiac transcription
      factors and cardiac-specific genes expression. CMs were electrically connected to
      one another. Recorded action potential (AP) showed waves of relatively mature
      ventricular-like phenotype. SIGNIFICANCE: We demonstrated that hiPSC lines
      respond differently to a standard cardiac differentiation protocol and that a
      well-orchestrated interplay between Wnt, BMP4, FGF/MEK and Ascorbic acid
      MEK/ERK1/2 signaling pathways is beneficial in enhancing the differentiation
      outcome.

PMID- 29337068
TI  - The impact of compression force and pressure at prevalent screening on subsequent
      re-attendance in a national screening program.
AB  - Adherence to screening may indirectly help assess whether a prior screening
      examination deters women from returning for a subsequent examination. We
      investigated whether compression force and pressure in mammography were
      associated with re-attendance among prevalently screened women in the organized
      breast cancer screening program in Norway. Data on compression force (kg) and
      pressure (kPa) from women's first screening examination in the program (prevalent
      screening) and subsequent re-attendance were available for 31,225 women aged 50
      68, screened during 2007-2013. Crude re-attendance rates and log-binomial
      regression models estimating the prevalence ratio of re-attendance were used to
      identify the association between compression force or pressure and re-attendance
      two-years later. Age and year at prevalent screening, county of residence,
      screening result (negative or false positive), breast volume, and breast density
      were included in analyses. Overall, 27,197 (87.1%) women re-attended the program.
      Re-attendance was highest for women who received a compression force of 10.0-13.9
      kg (87.5%) or pressure of 9.0-17.9 kPa (87.8%) and lowest for those who received
      a compression force of <10.0 kg (85.0%) or pressure of <9.0 kPa (84.7%). The
      adjusted prevalence of re-attendance was 3% lower for women who received low
      compression force (<10.0 kg) and 2% lower for women who received low compression
      pressure (<9.0 kPa) relative to the reference groups (10.0-13.9 kg and 9.0-17.9
      kPa, respectively). Future research related to re-attendance should also include
      information about women's experience of pain, anxiety and stress, as well as
      image quality.

PMID- 29337069
TI  - A survey instrument for measuring vaccine acceptance.
AB  - Accurately measuring vaccine acceptance is important, especially under current
      conditions in which misinformation may increase public anxiety about vaccines and
      politicize vaccination policies. We integrated substantive knowledge,
      conceptualization and measurement expertise, and survey design principles to
      develop an instrument for measuring vaccine acceptance across the general public.
      Given this broad goal, we expect our novel instrument will complement, rather
      than replace, existing instruments designed specifically to measure parents'
      vaccine hesitancy. Our instrument measures five key facets of vaccine acceptance:
      (1) perceived safety of vaccines; (2) perceived effectiveness and necessity of
      vaccines; (3) acceptance of the selection and scheduling of vaccines; (4)
      positive values and affect toward vaccines; and (5) perceived legitimacy of
      authorities to require vaccinations. We report results of analyses demonstrating
      the reliability and validity of this instrument. High Cronbach's alpha values for
      five sub-scales and for the full scale indicate the instrument's reliability, and
      the consistent performance of expected predictors (i.e., trust in biologists,
      conspiratorial ideation, and political ideology) demonstrates the instrument's
      construct validity. Further, scientific reasoning increases vaccine acceptance
      among liberals but decreases vaccine acceptance among conservatives, which is
      consistent with motivated cognition. Also, trust in biologists has a stronger
      positive effect on vaccine acceptance among conservatives than among liberals,
      signaling a potentially promising means to reduce political polarization on
      vaccines and increase vaccine acceptance across the general public. We end by
      identifying key ways that public health researchers, science studies scholars,
      and health practitioners may employ the full (or short) version of our vaccine
      acceptance instrument.

PMID- 29337070
TI  - Intrinsic and extrinsic contributors to defective CD8+ T cell responses with
      aging.
AB  - Aging has a profound effect on the immune system, and both innate and adaptive
      arms of the immune system show functional decline with age. In response to
      infection with intracellular microorganisms, old animals mobilize decreased
      numbers of antigen-specific CD8+ T cells with reduced production of effector
      molecules and impaired cytolytic activity. However, the CD8+ T cell-intrinsic
      contribution to, and molecular mechanisms behind, these defects remain unclear.
      In this review we will discuss the mechanistic contributions of age related
      changes in the CD8+ T cell pool and the relative roles of intrinsic functional
      defects in aged CD8+ T cells vs. defects in the aged environment initiating the
      CD8+ T cell response.

PMID- 29337071
TI  - Lower protein and higher carbohydrate intake are related with altering metabolic
      syndrome components in elderly women: A cross-sectional study.
AB  - BACKGROUND: Metabolic Syndrome (MetS) is an energy-disturbance disease associated
      with insulin resistance. Hence, the intake of energy-rich macronutrients might
      affect some MetS components. The aim of this study was to explore the association
      of ingested macronutrients with MetS components in older women. METHODS: A cross
      sectional study was conducted in 245 older women (>=60 years). Whole-body dual
      energy X-ray absorptiometry was used to assess total body fat, percentage body
      fat (absolute and relative), and skeletal muscle mass. Venous blood samples were
      collected after a 12 h fasting to determine glucose, high-density lipoprotein
      (HDL-c), and triglycerides. Anthropometric measurements and resting blood
      pressure were also evaluated. Food consumption was assessed through the 24-hour
      dietary recall method, and the macronutrients were distributed by tertiles of
      consumption. The Student t-test, Mann-Whitney U test, and logistic regression
      analysis were used for statistical analysis. RESULTS: The MetS and non-MetS
      groups demonstrated similar food-energy intake and fat consumption. The MetS
      group presented lower protein and higher carbohydrate intake than the non-MetS
      group. Individuals in the lowest protein intake (<0.72 g/kg/d) had greater odds
      of presenting abdominal obesity and impaired glucose levels. Higher consumption
      of carbohydrates was associated with lower HDL levels and higher
      hypertriglyceridemia. The chances of having MetS were increased by three times
      when ingesting either a low protein or high carbohydrate diet. CONCLUSION: Either
      high carbohydrate or low protein intake would be risk factors for altering MetS
      components and the presence of MetS in elderly women.

PMID- 29337072
TI  - Valorization of Brewer's spent grain to prebiotic oligosaccharide: Production,
      xylanase catalyzed hydrolysis, in-vitro evaluation with probiotic strains and in
      a batch human fecal fermentation model.
AB  - Brewer's spent grain (BSG) accounts for around 85% of the solid by-products from
      beer production. BSG was first extracted to obtain water-soluble arabinoxylan
      (AX). Using subsequent alkali extraction (0.5 M KOH) it was possible to dissolve
      additional AX. In total, about 57% of the AX in BSG was extracted with the purity
      of 45-55%. After comparison of nine xylanases, Pentopan mono BG, a GH11 enzyme,
      was selected for hydrolysis of the extracts to oligosaccharides with minimal
      formation of monosaccharides. Growth of Bifidobacterium adolescentis (ATCC 15703)
      was promoted by the enzymatic hydrolysis to arabinoxylooligosaccharides, while
      Lactobacillus brevis (DSMZ 1264) utilized only unsubstituted
      xylooligosaccharides. Furthermore, utilization of the hydrolysates by human gut
      microbiota was also assessed in a batch human fecal fermentation model. Results
      revealed that the rates of fermentation of the BSG hydrolysates by human gut
      microbiota were similar to that of commercial prebiotic fructooligosaccharides,
      while inulin was fermented at a slower rate. In summary, a sustainable process to
      valorize BSG to functional food ingredients has been proposed.

PMID- 29337073
TI  - Neofunctionalization of Duplicated P450 Genes Drives the Evolution of Insecticide
      Resistance in the Brown Planthopper.
AB  - Gene duplication is a major source of genetic variation that has been shown to
      underpin the evolution of a wide range of adaptive traits [1, 2]. For example,
      duplication or amplification of genes encoding detoxification enzymes has been
      shown to play an important role in the evolution of insecticide resistance [3-5].
      In this context, gene duplication performs an adaptive function as a result of
      its effects on gene dosage and not as a source of functional novelty [3, 6-8].
      Here, we show that duplication and neofunctionalization of a cytochrome P450,
      CYP6ER1, led to the evolution of insecticide resistance in the brown planthopper.
      Considerable genetic variation was observed in the coding sequence of CYP6ER1 in
      populations of brown planthopper collected from across Asia, but just two
      sequence variants are highly overexpressed in resistant strains and metabolize
      imidacloprid. Both variants are characterized by profound amino-acid alterations
      in substrate recognition sites, and the introduction of these mutations into a
      susceptible P450 sequence is sufficient to confer resistance. CYP6ER1 is
      duplicated in resistant strains with individuals carrying paralogs with and
      without the gain-of-function mutations. Despite numerical parity in the genome,
      the susceptible and mutant copies exhibit marked asymmetry in their expression
      with the resistant paralogs overexpressed. In the primary resistance-conferring
      CYP6ER1 variant, this results from an extended region of novel sequence upstream
      of the gene that provides enhanced expression. Our findings illustrate the
      versatility of gene duplication in providing opportunities for functional and
      regulatory innovation during the evolution of an adaptive trait.

PMID- 29337074
TI  - In Situ Clock Shift Reveals that the Sun Compass Contributes to Orientation in a
      Pelagic Seabird.
AB  - Compass orientation is central to the control of animal movement from the scale
      of local food-caching movements around a familiar area in parids [1] and corvids
      [2, 3] to the first autumn vector navigation of songbirds embarking on long
      distance migration [4-6]. In the study of diurnal birds, where the homing pigeon,
      Columba livia, has been the main model, a time-compensated sun compass [7] is
      central to the two-step map-and-compass process of navigation from unfamiliar
      places, as well as guiding movement via a representation of familiar area
      landmarks [8-12]. However, its use by an actively navigating wild bird is yet to
      be shown. By phase shifting an animal's endogenous clock, known as clock-shifting
      [13-15], sun-compass use can be demonstrated when the animal incorrectly consults
      the sun's azimuthal position while homing after experimental displacement [15
      17]. By applying clock-shift techniques at the nest of a wild bird during natural
      incubation, we show here that an oceanic navigator-the Manx shearwater, Puffinus
      puffinus-incorporates information from a time-compensated sun compass during
      homeward guidance to the breeding colony after displacement. Consistently with
      homing pigeons navigating within their familiar area [8, 9, 11, 18], we find that
      the effect of clock shift, while statistically robust, is partial in nature,
      possibly indicating the incorporation of guidance from landmarks into movement
      decisions.

PMID- 29337075
TI  - Brassinosteroids Dominate Hormonal Regulation of Plant Thermomorphogenesis via
      BZR1.
AB  - Thermomorphogenesis is defined as the suite of morphological changes that
      together are likely to contribute to adaptive growth acclimation to usually
      elevated ambient temperature [1, 2]. While many details of warmth-induced signal
      transduction are still elusive, parallels to light signaling recently became
      obvious (reviewed in [3]). It involves photoreceptors that can also sense changes
      in ambient temperature [3-5] and act, for example, by repressing protein activity
      of the central integrator of temperature information PHYTOCHROME-INTERACTING
      FACTOR 4 (PIF4 [6]). In addition, PIF4 transcript accumulation is tightly
      controlled by the evening complex member EARLY FLOWERING 3 [7, 8]. According to
      the current understanding, PIF4 activates growth-promoting genes directly but
      also via inducing auxin biosynthesis and signaling, resulting in cell elongation.
      Based on a mutagenesis screen in the model plant Arabidopsis thaliana for mutants
      with defects in temperature-induced hypocotyl elongation, we show here that both
      PIF4 and auxin function depend on brassinosteroids. Genetic and pharmacological
      analyses place brassinosteroids downstream of PIF4 and auxin. We found that
      brassinosteroids act via the transcription factor BRASSINAZOLE RESISTANT 1
      (BZR1), which accumulates in the nucleus at high temperature, where it induces
      expression of growth-promoting genes. Furthermore, we show that at elevated
      temperature BZR1 binds to the promoter of PIF4, inducing its expression. These
      findings suggest that BZR1 functions in an amplifying feedforward loop involved
      in PIF4 activation. Although numerous negative regulators of PIF4 have been
      described, we identify BZR1 here as a true temperature-dependent positive
      regulator of PIF4, acting as a major growth coordinator.

PMID- 29337077
TI  - Chimeric Synergy in Natural Social Groups of a Cooperative Microbe.
AB  - Many cooperative species form internally diverse social groups in which
      individual fitness depends significantly on group-level productivity from
      cooperation [1-4]. For such species, selection is expected to often disfavor
      within-group diversity that reduces cooperative productivity [5, 6]. While
      diversity within social groups is known to enhance productivity in some animals
      [7-9], diversity within natural groups of social microbes is largely unexamined
      in this regard. Cells of the soil bacterium Myxococcus xanthus respond to
      starvation by constructing multicellular fruiting bodies within each of which a
      subpopulation of cells transforms into stress-resistant spores [10]. Fruiting
      bodies isolated from soil often harbor substantial endemic diversity [11] that
      is, nonetheless, lower than between-group diversity, which increases with
      distance from millimeter to global scales [12-14]. We show that M. xanthus clones
      isolated from the same fruiting body often collectively produce more viable
      spores in chimeric groups than expected from sporulation in genetically
      homogeneous groups. In contrast, chimerism among clones derived from different
      fruiting bodies tends to reduce group productivity, and it does so increasingly
      as a function of spatial distance between fruiting-body sample sites. For one
      fruiting body examined in detail, chimeric synergy-a positive quantitative effect
      of chimerism on group productivity-is distributed broadly across an interaction
      network rather than limited to a few interactions. We propose that these results
      strengthen the plausibility of the hypothesis that selection may operate not only
      within Myxococcus groups, but also between kin groups to disfavor within-group
      variation that reduces productivity while allowing some forms of diversity that
      generate chimeric synergy to persist.

PMID- 29337076
TI  - Opposing Kinesin and Myosin-I Motors Drive Membrane Deformation and Tubulation
      along Engineered Cytoskeletal Networks.
AB  - Microtubule and actin filament molecular motors such as kinesin-1 and myosin-Ic
      (Myo1c) transport and remodel membrane-bound vesicles; however, it is unclear how
      they coordinate to accomplish these tasks. We introduced kinesin-1- and Myo1c
      bound giant unilamellar vesicles (GUVs) into a micropatterned in vitro
      cytoskeletal matrix modeled after the subcellular architecture where vesicular
      sorting and membrane remodeling are observed. This array was composed of sparse
      microtubules intersecting regions dense with actin filaments, and revealed that
      Myo1c-dependent tethering of GUVs enabled kinesin-1-driven membrane deformation
      and tubulation. Membrane remodeling at actin/microtubule intersections was
      modulated by lipid composition and the addition of the Bin-Amphiphysin-Rvs-domain
      (BAR-domain) proteins endophilin or FCH-domain-only (FCHo). Myo1c not only
      tethered microtubule-transported cargo, but also transported, deformed, and
      tubulated GUVs along actin filaments in a lipid-composition- and BAR-protein
      responsive manner. These results suggest a mechanism for actin-based involvement
      in vesicular transport and remodeling of intracellular membranes, and implicate
      lipid composition as a key factor in determining whether vesicles will undergo
      transport, deformation, or tubulation driven by opposing actin and microtubule
      motors and BAR-domain proteins.

PMID- 29337078
TI  - Circadian Waves of Transcriptional Repression Shape PIF-Regulated Photoperiod
      Responsive Growth in Arabidopsis.
AB  - Plants coordinate their growth and development with the environment through
      integration of circadian clock and photosensory pathways. In Arabidopsis
      thaliana, rhythmic hypocotyl elongation in short days (SD) is enhanced at dawn by
      the basic-helix-loop-helix (bHLH) transcription factors PHYTOCHROME-INTERACTING
      FACTORS (PIFs) directly inducing expression of growth-related genes [1-6]. PIFs
      accumulate progressively during the night and are targeted for degradation by
      active phytochromes in the light, when growth is reduced. Although PIF proteins
      are also detected during the day hours [7-10], their growth-promoting activity is
      inhibited through unknown mechanisms. Recently, the core clock components and
      transcriptional repressors PSEUDO-RESPONSE REGULATORS PRR9/7/5 [11, 12], negative
      regulators of hypocotyl elongation [13, 14], were described to associate to G
      boxes [15], the DNA motifs recognized by the PIFs [16, 17], suggesting that PRR
      and PIF function might converge antagonistically to regulate growth. Here we
      report that PRR9/7/5 and PIFs physically interact and bind to the same promoter
      region of pre-dawn-phased, growth-related genes, and we identify the
      transcription factor CDF5 [18, 19] as target of this interplay. In SD, CDF5
      expression is sequentially repressed from morning to dusk by PRRs and induced pre
      dawn by PIFs. Consequently, CDF5 accumulates specifically at dawn, when it
      induces cell elongation. Our findings provide a framework for recent TIMING OF
      CAB EXPRESSION 1 (TOC1/PRR1) data [5, 20] and reveal that the long described
      circadian morning-to-midnight waves of the PRR transcriptional repressors (PRR9,
      PRR7, PRR5, and TOC1) [21] jointly gate PIF activity to dawn to prevent
      overgrowth through sequential regulation of common PIF-PRR target genes such as
      CDF5.

PMID- 29337079
TI  - Rising pCO2 in Freshwater Ecosystems Has the Potential to Negatively Affect
      Predator-Induced Defenses in Daphnia.
AB  - Anthropogenically released CO2 accumulates in the global carbon cycle and is
      anticipated to imbalance global carbon fluxes [1]. For example, increased
      atmospheric CO2 induces a net air-to-sea flux where the oceans take up large
      amounts of atmospheric CO2 (i.e., ocean acidification [2-5]). Research on ocean
      acidification is ongoing, and studies have demonstrated the consequences for
      ecosystems and organismal biology with major impacts on marine food webs,
      nutrient cycles, overall productivity, and biodiversity [6-9]. Yet, surprisingly
      little is known about the impact of anthropogenically caused CO2 on freshwater
      systems due to their more complex biogeochemistry. The current consensus, yet
      lacking data evidence, is that anthropogenic CO2 does indeed affect freshwater
      carbon hydrogeochemistry, causing increased pCO2 in freshwater bodies [10-13]. We
      analyzed long-term data from four freshwater reservoirs and observed a continuous
      pCO2 increase associated with a decrease in pH, indicating that not only the
      oceans but also inland waters are accumulating CO2. We tested the effect of pCO2
      dependent freshwater acidification using the cosmopolite crustacean Daphnia. For
      general validity, control pCO2-levels were based on the present global pCO2
      average. Treatments were selected with very high pCO2 levels, assuming a
      continuous non-linear increase of pCO2, reflecting worst-case-scenario future
      pCO2 levels. Such levels of elevated pCO2 reduced the ability of Daphnia to sense
      its predators and form adequate inducible defenses. We furthermore determined
      that pCO2 and not the resulting reduction in pH impairs predator perception. If
      pCO2 alters chemical communication between freshwater species, this perturbs
      intra- and interspecific information transfer, which may affect all trophic
      levels.

PMID- 29337080
TI  - SMC1alpha Substitutes for Many Meiotic Functions of SMC1beta but Cannot Protect
      Telomeres from Damage.
AB  - The cohesin complex is built upon the SMC1/SMC3 heterodimer, and mammalian
      meiocytes feature two variants of SMC1 named SMC1alpha and SMC1beta. It is
      unclear why these two SMC1 variants have evolved. To determine unique versus
      redundant functions of SMC1beta, we asked which of the known functions of
      SMC1beta can be fulfilled by SMC1alpha. Smc1alpha was expressed under control of
      the Smc1beta promoter in either wild-type or SMC1beta-deficient mice. No effect
      was seen in the former. However, several major phenotypes of SMC1beta-deficient
      spermatocytes were rescued by SMC1alpha. We observed extended development before
      apoptosis and restoration of axial element and synaptonemal complex lengths,
      chromosome synapsis, sex body formation, processing of DNA double-strand breaks,
      and formation of MLH1 recombination foci. This supports the concept that the
      quantity rather than the specific quality of cohesin complexes is decisive for
      meiotic chromosome architecture. It also suggests plasticity in complex
      composition, because to replace SMC1beta in many functions, SMC1alpha has to more
      extensively associate with other cohesins. The cells did not complete meiosis but
      died to the latest at the pachytene-to-diplotene transition. Telomere aberrations
      known from Smc1beta-/- mice persisted, and DNA damage response and repair
      proteins accumulated there regardless of expression of SMC1alpha. Thus, whereas
      SMC1alpha can substitute for SMC1beta in many functions, the protection of
      telomere integrity requires SMC1beta.

PMID- 29337081
TI  - Abolishment of Spontaneous Flight Turns in Visually Responsive Drosophila.
AB  - Animals react rapidly to external stimuli, such as an approaching predator, but
      in other circumstances, they seem to act spontaneously, without any obvious
      external trigger. How do the neural processes mediating the execution of
      reflexive and spontaneous actions differ? We studied this question in tethered,
      flying Drosophila. We found that silencing a large but genetically defined set of
      non-motor neurons virtually eliminates spontaneous flight turns while preserving
      the tethered flies' ability to perform two types of visually evoked turns,
      demonstrating that, at least in flies, these two modes of action are almost
      completely dissociable.

PMID- 29337082
TI  - Serum lactate dehydrogenase isoenzymes 4 plus 5 is a better biomarker than total
      lactate dehydrogenase for refractory Mycoplasma pneumoniae pneumonia in children.
AB  - Although usually self-limiting, Mycoplasma pneumoniae pneumonia (MPP) may lead to
      clinical or radiological deterioration despite macrolide antibiotic therapy,
      resulting in the development of refractory MPP (RMPP). Corticosteroids have been
      used to treat RMPP with beneficial effects. Serum lactate dehydrogenase (LDH) is
      a suggested biomarker for the use of steroid therapy. Since serum LDH is a non
      specific marker and elevated in many inflammatory processes, this study
      investigates the predicting level of LDH isoenzymes for RMPP. Fifty-four children
      with non-refractory M. pneumoniae pneumonia (NRMPP) and 16 children with RMPP
      were enrolled in this study. In comparison to the NRMPP group, the RMPP group
      showed significantly higher levels of serum LDH. Concerning LDH isoenzymes, the
      RMPP group showed significantly lower proportions of LDH1 and LDH2, while higher
      LDH4 and LDH5 percentage. Receiver operating characteristic curve analysis showed
      that the area under the curve for the total LDH data was 0.812 with a cut-off of
      408 IU/L (sensitivity of 75.0%, specificity of 72.2%). The areas under the curve
      for LDH4, LDH5, and [LDH4 + LDH5] were estimated to be 0.813, 0.818, and 0.829,
      respectively. The threshold for [LDH4 + LDH5] was estimated to be 109.4 IU/L
      (sensitivity, 75.0%; specificity, 87.0%). These results indicate that for the
      initiation of corticosteroid therapy, serum [LDH4 + LDH5] level is a more
      sensitive biomarker than total LDH.

PMID- 29337083
TI  - Palmitoylethanolamide attenuates cocaine-induced behavioral sensitization and
      conditioned place preference in mice.
AB  - Cocaine addiction is a chronically relapsing disorder characterized by compulsive
      drug-seeking and drug-taking behaviors. Previous studies have demonstrated that
      cocaine, as well as other drugs of abuse, alters the levels of lipid-based
      signaling molecules, such as N-acylethanolamines (NAEs). Moreover, brain levels
      of NAEs have shown sensitivity to cocaine self-administration and extinction
      training in rodents. Given this background, the aim of this study was to
      investigate the effects of repeated or acute administration of
      palmitoylethanolamide (PEA), an endogenous NAE, on psychomotor sensitization and
      cocaine-induced contextual conditioning. To this end, the potential ability of
      repeated PEA administration (1 or 10 mg/kg, i.p.) to modulate the acquisition of
      cocaine-induced behavioral sensitization (BS) and conditioned place preference
      (CPP) was assessed in male C57BL/6J mice. In addition, the expression of cocaine
      induced BS and CPP following acute PEA administration were also studied. Results
      showed that repeated administration of both doses of PEA were able to block the
      acquisition of cocaine-induced BS. Furthermore, acute administration of both
      doses of PEA was able to abolish the expression of BS, while the highest dose
      also abolished the expression of cocaine-induced CPP. Taken together, these
      results indicate that exogenous administration of PEA attenuated psychomotor
      sensitization, while the effect of PEA in cocaine-induced CPP depended on whether
      PEA was administered repeatedly or acutely. These findings could be relevant to
      understand the role that NAEs play in processes underlying the development and
      maintenance of cocaine addiction.

PMID- 29337084
TI  - A graph-based approach to analyze flux-balanced pathways in metabolic networks.
AB  - An elementary flux mode (EFM) is a pathway with minimum set of reactions that are
      functional in steady-state constrained space. Due to the high computational
      complexity of calculating EFMs, different approaches have been proposed to find
      these flux-balanced pathways. In this paper, an approach to find a subset of EFMs
      is proposed based on a graph data model. The given metabolic network is mapped to
      the graph model and decisions for reaction inclusion can be made based on
      metabolites and their associated reactions. This notion makes the approach more
      convenient to categorize the output pathways. Implications of the proposed method
      on metabolic networks are discussed.

PMID- 29337085
TI  - DISC: Describing Infections of the Spine treated with Ceftaroline.
AB  - OBJECTIVES: Infections of the spine lead to considerable morbidity and a high
      cost to the global healthcare system. Currently, evidence for using ceftaroline,
      an advanced-generation cephalosporin active against methicillin-resistant
      Staphylococcus aureus (MRSA), in spine infections is limited. METHODS: Describing
      Infections of the Spine treated with Ceftaroline (DISC) is a multicentre,
      retrospective, cohort study that evaluated ceftaroline for treating spine
      infections. Patients were included if they were aged >=18 years, diagnosed with a
      spine infection and treated with ceftaroline for >=28 days. A control group was
      identified with the same inclusion criteria as the study population except they
      were treated with a comparator antibiotic for >=28 days. RESULTS: Thirty-seven
      patients were included each in the ceftaroline and control groups. MRSA was the
      most commonly identified pathogen. With no differences between groups in age,
      sex, race or co-morbidities (with the exception of chronic kidney disease),
      treatment with ceftaroline led to similar clinical success compared with the
      control group. Multivariate regression analysis did not show a significant
      difference between the two groups in terms of clinical success after controlling
      for other covariates (adjusted odds ratio=1.49; P=0.711). More patients who
      received ceftaroline were discharged to an extended-care or rehabilitation
      facility than home compared with controls (81% vs. 54%, respectively; P=0.024).
      Side effects and toxicities were rare, including one case of eosinophilic
      pneumonia in the ceftaroline group. CONCLUSIONS: Ceftaroline appears to be a safe
      and effective therapy for infections of the spine, including from MRSA.

PMID- 29337086
TI  - Incidental Pulmonary Nodules Are Common on CT Coronary Angiogram and Have a
      Significant Cost Impact.
AB  - BACKGROUND: Computed tomography (CT) coronary angiogram (CTCA) is commonly used
      for diagnostic evaluation of low-moderate risk patients due to its excellent
      performance and cost-effectiveness. However, previous cost analyses have not
      factored in the burden of management of pulmonary nodules, which are a common
      occurrence. We sought to describe the frequency and characteristics of lung
      nodules on CTCA in an Australian tertiary hospital, and to assess cost impacts.
      METHODS: Consecutive CTCAs performed in the calendar year 2012 were
      retrospectively identified from the imaging department database. Subjects were
      excluded if they were under the age of 35, had known malignancy or findings
      identified prior to CTCA. Patients were stratified on smoking history and nodule
      size. RESULTS: Of the 2479 CTCAs included, full-field imaging revealed nodules in
      358 patients (13.9%). The nodules were generally small (73% <6mm), multiple (63%)
      and in the lower lobe (83.4%). There was no significant difference when
      stratified for smoking, with 60% of nodules detected in never-smokers. A minimum
      of 445 subsequent scans was required for nodule surveillance, resulting in an
      additional overall cost of $63.62 per CTCA. Limited-Field-of-View (L-FOV) would
      have identified only 22 nodules, with a cost of $6.14 for every CTCA performed, a
      cost saving of $57 per patient. CONCLUSIONS: Indeterminate pulmonary nodules are
      a common incidental finding on CTCA and prevalence appears to be independent of
      smoking status. There is a consequent significant cost burden that has not
      previously been recognised. Use of L-FOV reduces the number of nodules
      identified, with a significant cost benefit, but this has to be balanced against
      the ethical and medico-legal issues inherent in not reconstructing the irradiated
      lung.

PMID- 29337087
TI  - Genetic polymorphisms of pharmacogenomic VIP variants in the Yi population from
      China.
AB  - INTRODUCTION: Drug response and target therapeutic dosage are different among
      individuals. The variability is largely genetically determined. With the
      development of pharmacogenetics and pharmacogenomics, widespread research have
      provided us a wealth of information on drug-related genetic polymorphisms, and
      the very important pharmacogenetic (VIP) variants have been identified for the
      major populations around the world whereas less is known regarding minorities in
      China, including the Yi ethnic group. Our research aims to screen the potential
      genetic variants in Yi population on pharmacogenomics and provide a theoretical
      basis for future medication guidance. MATERIALS AND METHODS: In the present
      study, 80 VIP variants (selected from the PharmGKB database) were genotyped in
      100 unrelated and healthy Yi adults recruited for our research. Through
      statistical analysis, we made a comparison between the Yi and other 11
      populations listed in the HapMap database for significant SNPs detection. Two
      specific SNPs were subsequently enrolled in an observation on global allele
      distribution with the frequencies downloaded from ALlele FREquency Database.
      Moreover, F-statistics (Fst), genetic structure and phylogenetic tree analyses
      were conducted for determination of genetic similarity between the 12 ethnic
      groups. RESULTS: Using the chi2 tests, rs1128503 (ABCB1), rs7294 (VKORC1),
      rs9934438 (VKORC1), rs1540339 (VDR) and rs689466 (PTGS2) were identified as the
      significantly different loci for further analysis. The global allele distribution
      revealed that the allele "A" of rs1540339 and rs9934438 were more frequent in Yi
      people, which was consistent with the most populations in East Asia. F-statistics
      (Fst), genetic structure and phylogenetic tree analyses demonstrated that the Yi
      and CHD shared a closest relationship on their genetic backgrounds. Additionally,
      Yi was considered similar to the Han people from Shaanxi province among the
      domestic ethnic populations in China. CONCLUSIONS: Our results demonstrated
      significant differences on several polymorphic SNPs and supplement the
      pharmacogenomic information for the Yi population, which could provide new
      strategies for optimizing clinical medication in accordance with the genetic
      determinants of drug toxicity and efficacy.

PMID- 29337088
TI  - Cross-regulatory network in Pseudomonas aeruginosa biofilm genes and TiO2 anatase
      induced molecular perturbations in key proteins unraveled by a systems biology
      approach.
AB  - A systems biology approach was used to study all the biofilm related genes of P.
      aeruginosa PAO1, and the interaction of titanium dioxide (TiO2) anatase with
      biofilm related proteins. Among the 71 genes, the interactions of all the nodal
      pairs were extracted by STRING 10.5 database. The inter-relationship among these
      genes was predicted by constructing complete PPI network and visualized in
      Cytoscape v 3.4.0. Total number of nodes of the network was found to be 335 and
      edges were 795. The network was further investigated for its clusters and the
      best cluster was further analyzed for the hub proteins which significantly
      contribute in cross-regulation of the biofilm related process. The hub proteins
      were identified based on four topological parameters of degree, closeness,
      betweeness and radiality. Four major hub proteins of P. aeruginosa PAO1 were
      identified to be algD, gacS, rpoS and rpoN which were common in all the hubs.
      Further, we have also elucidated the probable mechanism of TiO2 interaction with
      P. aeruginosa PAO1 at molecular level. Using STITCH server, the major target gene
      of TiO2 was identified as katA which also appeared commonly in our main dataset
      and this gene has been focused for the further study because of its unique common
      appearance in gene-gene network as well as gene-anatase network. The direct
      interacting partners of katA were found to be dnaK, hfq, rpoS and rpoA. Based on
      these findings and available gene regulatory information, probable TiO2
      interacting cascade has been represented. This in silico study of P. aeruginosa
      PAO1 biofilm genes and the interaction of protein products with TiO2 might be
      significant to understand the perspective pathogenic resistance as well as the
      toxicity research pertaining to nanoparticles.

PMID- 29337089
TI  - Thermal Field Distributions of Ablative Experiments Using Cyst-mimicking
      Phantoms: Comparison of Microwave and Radiofrequency Ablation.
AB  - RATIONALE AND OBJECTIVES: The objective of this study was to explore the thermal
      field distribution of cystic lesions undergoing microwave ablation (MWA) and
      radiofrequency ablation (RFA) using in vitro phantoms. MATERIALS AND METHODS:
      Cyst-mimicking lesions filled with sodium chloride (NaCl) solution in acrylamide
      phantoms were treated with MWA and RFA in vitro. The radiofrequency electrodes or
      MWA antennas were implanted in the centers of the artificial cystic lesions. We
      used temperature fields located 5, 15, and 25 mm from the electrode or the
      antenna to plot the temperature-rise curves. Solid phantoms without cysts were
      also fabricated as controls. RESULTS: The temperature within cysts increased
      faster and reached a higher maximum temperature during MWA than during RFA, and
      this result was independent of the NaCl solution concentration. RFA treatment
      caused the temperatures within the lesion to increase significantly faster in the
      cysts containing 0.9% NaCl than in those containing 5.0% NaCl. However, the MWA
      temperature-rise curves were only weakly affected by the ionic concentration. The
      median temperature difference values between the 5- and 15-mm points were
      markedly lower in the 0.9% NaCl cyst-mimicking phantom (P <0.001) than in the
      solid phantom after either MWA or RFA. CONCLUSIONS: Our data indicate that MWA is
      a more effective technique for focal cystic lesions than RFA and has higher
      overall energy utilization. MWA was also less affected by the ionic concentration
      of the cystic fluid.

PMID- 29337090
TI  - The Clinical Impact of Resident-attending Discrepancies in On-call Radiology
      Reporting: A Retrospective Assessment.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study is to quantify the clinical
      impact of resident-attending discrepancies at a tertiary referral academic
      radiology residency program by assessing rates of intervention, discrepancy
      confirmation, recall rate, and management change rate; furthermore, a discrepancy
      categorization system will be assessed. MATERIALS AND METHODS: Retrospective
      review of the records was performed for n = 1482 discrepancies that occurred in
      the 17-month study period to assess the clinical impact of discrepancies.
      Discrepancies were grouped according to a previously published classification
      system. Management changes were recorded and grouped by severity. The recall rate
      was estimated for discharged patients. Any confirmatory testing was reviewed to
      evaluate the accuracy of the discrepant report. Categorical variables were
      compared to the chi-square test. RESULTS: The 1482 discrepancies led to
      management change in 661 cases (44.6%). The most common management change was
      follow-up imaging. Procedural interventions including surgery occurred in 50
      cases (3.3%). The recall rate was 2.6%. Management changes were more severe with
      computed tomography examinations, inpatients, and when the discrepancy was in the
      chest and abdomen subspecialty. Also, management changes correlated with the
      discrepancy category assigned by the attending at the time of review.
      CONCLUSIONS: Resident-attending discrepancies do cause management changes in
      44.6% of discrepancies (0.62% overall); the most frequent change is follow-up
      imaging. The discrepancy categorization assigned by the attending correlated with
      the severity of management change.

PMID- 29337091
TI  - A Clinically Meaningful Interpretation of the Prospective Investigation of
      Pulmonary Embolism Diagnosis (PIOPED) II and III Data.
AB  - RATIONALE AND OBJECTIVES: This study aimed to calculate the multiple-level
      likelihood ratios (LRs) and posttest probabilities for a positive, indeterminate,
      or negative test result for multidetector computed tomography pulmonary
      angiography (MDCTPA) +/- computed tomography venography (CTV) and magnetic
      resonance pulmonary angiography (MRPA) +/- magnetic resonance venography (MRV)
      for each clinical probability level (two-, three-, and four-level) for the nine
      most commonly used clinical prediction rules (CPRs) (Wells, Geneva, Miniati, and
      Charlotte). The study design is a review of observational studies with critical
      review of multiple cohort studies. The settings are acute care, emergency room
      care, and ambulatory care (inpatients and outpatients). MATERIALS AND METHODS:
      Data were used to estimate pulmonary embolism (PE) pretest probability for each
      of the most commonly used CPRs at each probability level. Multiple-level LRs
      (positive, indeterminate, negative test) were generated and used to calculate
      posttest probabilities for MDCTPA, MDCTPA + CTV, MRPA, and MRPA + MRV from
      sensitivity and specificity results from Prospective Investigation of Pulmonary
      Embolism Diagnosis (PIOPED) II and PIOPED III for each clinical probability level
      for each CPR. Nomograms were also created. RESULTS: The LRs for a positive test
      result were higher for MRPA compared to MDCTPA without venography (76 vs 20) and
      with venography (42 vs 18). LRs for a negative test result were lower for MDCTPA
      compared to MRPA without venography (0.18 vs 0.22) and with venography (0.12 vs
      0.15). In the three-level Wells score, the pretest clinical probability of PE for
      a low, moderate, and high clinical probability score is 5.7, 23, and 49. The
      posttest probability for an initially low clinical probability PE for a positive,
      indeterminate, and negative test result, respectively, for MDCTPA is 54, 5 and 1;
      for MDCTPA + CTV is 52, 2, and 0.7; for MRPA is 82, 6, and 1; and for MRPA + MRV
      is 72, 3, and 1; for an initially moderate clinical probability PE for MDCTPA is
      86, 22, and 5; for MDCTPA + CTV is 85, 10, and 4; for MRPA is 96, 25, and 6; and
      for MRPA + MRV is 93, 14, and 4; and for an initially high clinical probability
      of PE for MDCTPA is 95, 47, and 15; for MDCTPA + CTV is 95, 27, and 10; for MRPA
      is 99, 52, and 17; and for MRPA + MRV is 98, 34, and 13. CONCLUSIONS: For a
      positive test result, LRs were considerably higher for MRPA compared to MDCTPA.
      However, both a positive MRPA and MDCTPA have LRs >10 and therefore can confirm
      the presence of PE. Performing venography reduced the LR for a positive and
      negative test for both MDCTPA and MRPA. The nomograms give posttest probabilities
      for a positive, indeterminate, or negative test result for MDCTPA and MRPA (with
      and without venography) for each clinical probability level for each of the CPR.

PMID- 29337093
TI  - Breast cancer in young women: do BRCA1 or BRCA2 mutations matter?

PMID- 29337092
TI  - Germline BRCA mutation and outcome in young-onset breast cancer (POSH): a
      prospective cohort study.
AB  - BACKGROUND: Retrospective studies provide conflicting interpretations of the
      effect of inherited genetic factors on the prognosis of patients with breast
      cancer. The primary aim of this study was to determine the effect of a germline
      BRCA1 or BRCA2 mutation on breast cancer outcomes in patients with young-onset
      breast cancer. METHODS: We did a prospective cohort study of female patients
      recruited from 127 hospitals in the UK aged 40 years or younger at first
      diagnosis (by histological confirmation) of invasive breast cancer. Patients with
      a previous invasive malignancy (except non-melanomatous skin cancer) were
      excluded. Patients were identified within 12 months of initial diagnosis. BRCA1
      and BRCA2 mutations were identified using blood DNA collected at recruitment.
      Clinicopathological data, and data regarding treatment and long-term outcomes,
      including date and site of disease recurrence, were collected from routine
      medical records at 6 months, 12 months, and then annually until death or loss to
      follow-up. The primary outcome was overall survival for all BRCA1 or BRCA2
      mutation carriers (BRCA-positive) versus all non-carriers (BRCA-negative) at 2
      years, 5 years, and 10 years after diagnosis. A prespecified subgroup analysis of
      overall survival was done in patients with triple-negative breast cancer.
      Recruitment was completed in 2008, and long-term follow-up is continuing.
      FINDINGS: Between Jan 24, 2000, and Jan 24, 2008, we recruited 2733 women.
      Genotyping detected a pathogenic BRCA mutation in 338 (12%) patients (201 with
      BRCA1, 137 with BRCA2). After a median follow-up of 8.2 years (IQR 6.0-9.9), 651
      (96%) of 678 deaths were due to breast cancer. There was no significant
      difference in overall survival between BRCA-positive and BRCA-negative patients
      in multivariable analyses at any timepoint (at 2 years: 97.0% [95% CI 94.5-98.4]
      vs 96.6% [95.8-97.3]; at 5 years: 83.8% [79.3-87.5] vs 85.0% [83.5-86.4]; at 10
      years: 73.4% [67.4-78.5] vs 70.1% [67.7-72.3]; hazard ratio [HR] 0.96 [95% CI
      0.76-1.22]; p=0.76). Of 558 patients with triple-negative breast cancer, BRCA
      mutation carriers had better overall survival than non-carriers at 2 years (95%
      [95% CI 89-97] vs 91% [88-94]; HR 0.59 [95% CI 0.35-0.99]; p=0.047) but not 5
      years (81% [73-87] vs 74% [70-78]; HR 1.13 [0.70-1.84]; p=0.62) or 10 years (72%
      [62-80] vs 69% [63-74]; HR 2.12 [0.82-5.49]; p= 0.12). INTERPRETATION: Patients
      with young-onset breast cancer who carry a BRCA mutation have similar survival as
      non-carriers. However, BRCA mutation carriers with triple-negative breast cancer
      might have a survival advantage during the first few years after diagnosis
      compared with non-carriers. Decisions about timing of additional surgery aimed at
      reducing future second primary-cancer risks should take into account patient
      prognosis associated with the first malignancy and patient preferences. FUNDING:
      Cancer Research UK, the UK National Cancer Research Network, the Wessex Cancer
      Trust, Breast Cancer Now, and the PPP Healthcare Medical Trust Grant.

PMID- 29337094
TI  - Vitamin D attenuates pressure overload-induced cardiac remodeling and dysfunction
      in mice.
AB  - Vitamin D (VD) and its analogues play critical roles in metabolic and
      cardiovascular diseases. Recent studies have demonstrated that VD exerts a
      protective role in cardiovascular diseases. However, the beneficial effect of VD
      on pressure overload-induced cardiac remodeling and dysfunction and its
      underlying mechanisms are not fully elucidated. In this study, cardiac
      dysfunction and hypertrophic remodeling in mice were induced by pressure
      overload. Cardiac function was evaluated by echocardiography, and myocardial
      histology was detected by H&E and Masson's trichrome staining. Cardiomyocyte size
      was detected by wheat germ agglutinin staining. The protein levels of signaling
      mediators were examined by western blotting while mRNA expression of hypertrophic
      and fibrotic markers was examined by qPCR analysis. Oxidative stress was detected
      by dihydroethidine staining. Our results showed that administration of VD3
      significantly ameliorates pressure overload-induced contractile dysfunction,
      cardiac hypertrophy, fibrosis and inflammation in mice. In addition, VD3
      treatment also markedly inhibited cardiac oxidative stress and apoptosis.
      Moreover, protein levels of calcineurin A, ERK1/2, AKT, TGF-beta, GRP78, cATF6,
      and CHOP were significantly reduced whereas SERCA2 level was upregulated in the
      VD3-treated hearts compared with control. These results suggest that VD3
      attenuates cardiac remodeling and dysfunction induced by pressure overload, and
      this protective effect is associated with inhibition of multiple signaling
      pathways.

PMID- 29337095
TI  - Development of native and modified banana starch nanoparticles as vehicles for
      curcumin.
AB  - In recent years, starch nanoparticles have been of great interest for drug
      delivery due to their relatively easy synthesis, biocompatibility, and vast
      amount of botanical sources. Native and acetylated starch obtained from green
      bananas were used for synthesis of curcumin-loaded starch nanoparticles. Mean
      particle size, encapsulation efficiency, and curcumin release in simulated
      gastric and intestinal fluids were studied. Both nanosystems showed sizes lower
      than 250 nm and encapsulation efficiency above 80%, with acetylated banana starch
      nanoparticles having the capacity to encapsulate more curcumin molecules. Both
      FTIR and XRD analyses showed that starch acetylation allows stronger hydrogen
      bond interaction between curcumin and the starch matrix, thus, higher
      encapsulation efficiency. Finally, curcumin release studies showed that
      acetylated banana starch nanoparticles allowed more controlled release, probably
      due to their stronger hydrogen bond interaction with curcumin.

PMID- 29337096
TI  - Fabrication and characterization of nanoengineered biocompatible n-HA/chitosan
      tamarind seed polysaccharide: Bio-inspired nanocomposites for bone tissue
      engineering.
AB  - In this communication we describe the fabrication of nano-hydroxyapatite/chitosan
      tamarind seed polysaccharide (n-HA/CS-TSP) nanocomposite with a weight ratio of
      70/20/10, 70/15/15 and 70/10/20, respectively through a co-precipitation method.
      A comparative assessment of the properties of n-HA/CS-TSP and n-HA/CS
      nanocomposites was done by FT-IR, SEM-EDX, TEM, TGA/DTA, XRD and mechanical
      testing. The results suggested strong chemical interactions between the three
      components, decreased particle size and homogeneous dispersion of n-HA particles
      in n-HA/CS-TSP as compared to n-HA/CS. The n-HA/CS-TSP (70/10/20) showed the most
      porous and rough surface, enhanced thermal stability and highest compressive
      strength (4.0 MPa) and modulus (81 MPa). In addition, n-HA/CS-TSP (70/10/20)
      exhibited greater swelling character, acceptable degradation and increased
      biomineralization in simulated body fluid (SBF) as compared to n-HA/CS-TSP
      (70/20/10, 70/15/15) and n-HA/CS nanocomposites. The superior non-toxic response
      with MG-63 cells and better haemocompatibility was observed with n-HA/CS-TSP
      (70/15/15). Thereby, n-HA/CS-TSP nanocomposites could be promising alternative
      biomaterials in the field of bone tissue engineering compared to the n-HA/CS
      nanocomposite.

PMID- 29337097
TI  - Physical and antimicrobial properties of starch-carboxy methyl cellulose film
      containing rosemary essential oils encapsulated in chitosan nanogel.
AB  - This study was set to prepare a new active film by using a biodegradable bio
      based source, i.e., corn starch. To achieve that, benzoic acid (BA) and chitosan
      (CS) were covalently bound and CS-BA nanogel was then obtained using self
      assembly method. Subsequently, rosemary essential oil (REO) was encapsulated in
      CS-BA nanogel. Finally, REO in both free and encapsulated forms were incorporated
      in starch-carboxy methyl cellulose (CMC) films and their physical, mechanical and
      antimicrobial properties were studied. The films incorporating CS-BA nanogel had
      a higher water vapor permeability compared with the films containing REO.
      Moreover, film containing 0.2% CS-BA nanogel had the highest transparency and
      tensile strength. The REO and nanogel alone had inhibitory effects against
      Staphylococcus aureus (S. aureus) and by encapsulation, the inhibitory effect of
      REO was increased. By encapsulating REO in nanogel, both immediately (REO) and
      gradual (Nanogel) antimicrobial effect against S. aureus in the starch-CMC
      suspensions were obtained.

PMID- 29337098
TI  - Synthesis and characterization of chitin/curcumin blended polyurethane
      elastomers.
AB  - In this work, chitin-curcumin based polyurethane elastomers (PUEs) were prepared
      by step growth polymerization technique using hydroxy terminated polybutadiene
      (HTPB), hexamethylene diisocyanate (HDI), chitin and curcumin. The molecular
      characterization was done by using FTIR and SS 1HNMR techniques. The surface
      morphology and thermal stability was studied by scanning electron microscopy
      (SEM) and thermal gravimetric analysis (TGA), respectively. Degree of absorption
      and swelling characters were also determined in water as well as in DMSO. The
      crystalline behavior of prepared elastomers was checked by using X-ray
      diffraction (XRD) and differential scanning calorimeter (DSC). Results presented
      that crystallinity of elastomers increased by increasing the content of chitin
      due to formation of more ordered structure.

PMID- 29337099
TI  - Facile preparation and characterization of pH sensitive Mt/CMC nanocomposite
      hydrogel beads for propranolol controlled release.
AB  - The main aim of the present study was to design pH-sensitive nanocomposite
      hydrogel beads, based on carboxymethyl cellulose (CMC) and montmorillonite (Mt)
      propranolol (PPN) nanohybrid, and evaluate whether the prepared nanocomposite
      beads could potentially be used as oral drug delivery systems. PPN-as a model
      drug-was intercalated into the interlayer space of Mt clay mineral via the ion
      exchange procedure. The resultant nanohybrid (Mt-PPN) was applied to fabricate
      nanocomposite hydrogel beads by association with carboxymethyl cellulose. The
      characterization of test samples was performed using different techniques: X-Ray
      Diffraction (XRD), IR spectroscopy (FT-IR), thermal gravity analysis (TGA), and
      scanning electron microscopy (SEM). The drug encapsulation efficiency was
      evaluated by UV-vis spectroscopy, and was found to be high for Mt/CMC beads. In
      vitro drug release test was performed in the simulated gastrointestinal
      conditions to evaluate the efficiency of Mt-PPN/CMC nanocomposite beads as a
      controlled-release drug carrier. The drug release profiles indicated that the Mt
      PPN/CMC nanocomposite beads had high stability against stomach acid and a
      sustained- and controlled-release profile for PPN under the simulated intestinal
      conditions.

PMID- 29337100
TI  - Knockdown of long non-coding RNA XIST inhibits cell viability and invasion by
      regulating miR-137/PXN axis in non-small cell lung cancer.
AB  - Long non-coding RNAs (lncRNAs) may serve as miRNA sponges to modulate the
      expressions of miRNA target genes. LncRNA X-inactive specific transcript (XIST)
      has been demonstrated to be upregulated and act as an oncogene in non-small cell
      lung cancer (NSCLC). However, the sponge role of XIST in NSCLC progression
      remains largely unknown. In this study, we demonstrated that XIST was
      substantially upregulated and miR-137 was aberrantly downregulated in NSCLC
      tissues and cells. XIST was identified to function as a competitive endogenous
      RNA (ceRNA) for miR-137 to promote NSCLC cell viability and invasion.
      Additionally, our results suggested that miR-137 targeted the 3'UTR of paxillin
      (PXN) to suppress NSCLC cell viability and invasion. Meanwhile, miR-137 was
      negatively correlated with PXN expression while XIST was positively correlated
      with PXN expression. More importantly, XIST positively regulated PXN levels by
      sponging miR-137 in vitro and in vivo. Collectively, our study provided the
      evidence for the cross-talk between XIST, miR-137, and PXN, shedding light on the
      therapy for NSCLC.

PMID- 29337101
TI  - Extracellular polysaccharide from Weissella confusa OF126: Production,
      optimization, and characterization.
AB  - The production, optimization, and characterization of exopolysaccharide (EPS)
      from Weissella confusa OF126 and the in-vitro probiotic potentials of this strain
      was investigated. The EPS produced on sucrose modified-MRS broth was
      characterized. The purified EPS had an average molecular weight of 1.1 * 106 Da.
      HPLC analysis revealed the presence of glucose monomers, indicating its
      homopolysaccharide nature. The structural characteristics of the EPS were
      investigated by FTIR, and NMR spectroscopy. FTIR spectroscopy revealed the
      presence of hydroxyl, carboxyl, N-acetyl and amine groups. NMR analysis confirmed
      that the EPS contained alpha-(1 -> 6) linkage and alpha-(1 -> 3) branched
      linkage. The EPS showed strong in-vitro antioxidant activity. Four significant
      factors were optimized using Central Composite Design (CCD) and Response Surface
      Methodology (RSM). The predicted optimum conditions for EPS production were
      cultivation time (48.50 h), sucrose concentration (24.00 g/L), pH (7.00) and
      yeast extract (2.50%).The EPS produced was predicted to be 3.10 g/L, while the
      experimental yield was 3.00 g/L. This strain was found to possess desirable
      probiotic attributes by its ability to survive at pH 2.0 and in the presence of
      bile salts (0.50% (w/v)) for 4 h. The results obtained from this study
      demonstrate W. confusa OF126 as a promising probiotic and the EPS produced can
      find useful applications in industries.

PMID- 29337102
TI  - Polymeric microspheres of okra mucilage and alginate for the controlled release
      of oxcarbazepine: In vitro &in vivo evaluation.
AB  - Oxcarbazepine-loaded alginate/okra pods mucilage microspheres were prepared
      through inotropic gelation technique for the sustained release of oxcarbazepine.
      The drug encapsulating efficiency of these microspheres was found 76.22 +/- 0.01%
      to 90.57 +/- 0.02% and their average particle sizes were 496 MUm +/- 0.41 to 692
      MUm +/- 0.22. These microspheres were characterized in terms of swelling
      capacity, FTIR, DSC and SEM analysis. The in vitro drug release from these
      microspheres was followed sustained release (Korsemeyer - Peppas model) pattern
      (R2 = 0.9552-0.9906) and value of n > 1 showed that drug released by anomalous
      (non-Fickian) diffusion. The in vivo studies showed that there were highly
      significant difference with p < 0.001 in the pharmacokinetic parameters (Cmax,
      t1/2, AUC0-infinity, Ke), when oxcarbazepine was formulated in form of polymeric
      microspheres as compared to pure drug.

PMID- 29337103
TI  - Green options for imparting antibacterial functionality to cotton fabrics.
AB  - This study demonstrated that antibacterial cellulosic textiles can be fabricated
      in eco-friendly manner by grafting of monochlorotriazinyl beta-cyclodextin (MCT
      betaCD) onto knitted and woven cotton fabrics followed by post-loading of any of
      the green active ingredients namely Rosemary oil, Lavender oil, Clove oil,
      Cinnamon oil, Aloe vera gel, Vanillin, Ag-ions, Natural Yellow 7 and Natural Red
      25 dyes into the hydrophobic cavities of grafted beta-CD moieties. Some of the
      grafted, post-loaded fabric samples were characterized by FTIR, SEM, and EDS
      analysis. The enhancement in the imparted antibacterial functionality as well as
      durability to wash are governed by type of cellulosic substrate, kind, chemistry,
      antibacterial activity as well as extent of inclusion and subsequent release of
      the hosted bioactive agent. The obtained results revealed that the antibacterial
      efficacy follows the deceasing orders: i) knitted fabric > woven fabric and ii)
      Ag-ions > Lavender oil > Natural Yellow 7 > Aloe vera > Cinnamon oil > Natural
      Red 25 > Vanillin > Clove oil > Rosemary oil-loaded fabric sample, keeping other
      parameters constant.

PMID- 29337104
TI  - Bioactive potential and composition analysis of sulfated polysaccharide from
      Acanthophora spicifera (Vahl) Borgeson.
AB  - Marine seaweeds contain a valuable source of functional bioactive polysaccharide
      and it plays main role for effective anticancer activity. The structural feature
      of SPs was studied through FT-IR and 1H NMR spectra analysis. The isolated SPs
      from A. spicifera contain 63.3% of total sugar, 21.9% of total sulfate and 12.6%
      of total uranic acid was found. The active F2 fraction molecular weight of SP was
      found to be 420 kDa. The sugar was composed of galactose (73.5%), xylose (9.2%),
      mannose (1.9%) and arabinose (10.9%). Further the SP showed DPPH free radical
      scavenging activity of 55.55% at 150 MUg/mL and reducing power activity of 91.3%
      at 125 MUg/mL. In the present study, the purified sulfated polysaccharide
      (fraction F2) were extracted, purified and characterized for red seaweed and
      evaluated for their potential anticancer activity of in A549 cell lines under in
      vitro condition. These polysaccharide fractions exhibited potential apoptotic
      effects on A549 cell lines.

PMID- 29337105
TI  - Chitosan/sodium tripolyphosphate nanoparticles as efficient vehicles for
      antioxidant peptidic fraction from common kilka.
AB  - Fish-purified antioxidant peptide (AOP)-loaded chitosan nanoparticles (CSNPs)
      were synthesized based on the ionotropic gelation between CS and sodium
      tripolyphosphate (TPP). The zeta-potential showed an earlier rise and later
      decrease with increasing concentrations of AOP. Transmission electron microscopy
      (TEM) images also revealed roughly uniform spherical-shaped nanoparticles with
      diameter of <100 nm. Molecular interactions among the components of the NPs and
      peptides were confirmed by FT-IR spectroscopy. Thermo-gravimetric analysis (TGA)
      results showed the improved thermal stability of the AOP-loaded CSNPs compared
      with free peptides. The maximum peptide encapsulation efficiency was determined
      to be 71.16% and the in vitro release of peptides from CSNPs was in a
      controllable manner. Furthermore, assessing the free radical scavenging ability
      of the peptide-encapsulated NPs and the reducing power assay, confirmed the
      efficacy of such nanosystem in retaining the antioxidant activity of fish-derived
      peptides.

PMID- 29337106
TI  - Loss of TGF-beta signaling in osteoblasts increases basic-FGF and promotes
      prostate cancer bone metastasis.
AB  - TGF-beta plays a central role in prostate cancer (PCa) bone metastasis, and it is
      crucial to understand the bone cell-specific role of TGF-beta signaling in this
      process. Thus, we used knockout (KO) mouse models having deletion of the Tgfbr2
      gene specifically in osteoblasts (Tgfbr2Col1CreERT KO) or in osteoclasts
      (Tgfbr2LysMCre KO). We found that PCa-induced bone lesion development was
      promoted in the Tgfbr2Col1CreERT KO mice, but was inhibited in the Tgfbr2LysMCre
      KO mice, relative to their respective control Tgfbr2FloxE2 littermates. Since
      metastatic PCa cells attach to osteoblasts when colonized in the bone
      microenvironment, we focused on the mechanistic studies using the
      Tgfbr2Col1CreERT KO mouse model. We found that bFGF was upregulated in
      osteoblasts from PC3-injected tibiae of Tgfbr2Col1CreERT KO mice and correlated
      with increased tumor cell proliferation, angiogenesis, amounts of cancer
      associated fibroblasts and osteoclasts. In vitro studies showed that
      osteoblastogenesis was inhibited, osteoclastogenesis was stimulated, but PC3
      viability was not affected, by bFGF treatments. Lastly, the increased PC3-induced
      bone lesions in Tgfbr2Col1CreERT KO mice were significantly attenuated by
      blocking bFGF using neutralizing antibody, suggesting bFGF is a promising target
      inhibiting bone metastasis.

PMID- 29337107
TI  - tRNA-derived small non-coding RNAs in human disease.
AB  - Besides attending protein synthesis, transfer RNA (tRNA) is an important
      regulatory non-coding RNA (ncRNA) that participates in various cellular
      processes, including cellular metabolism and cell death. Fragments generated from
      pre- or mature tRNAs by specific endonucleases cleavage (tRNA-derived small non
      coding RNA [tsncRNAs]), rather than random degradation products, are newly
      defined functional small non-coding RNAs (sncRNAs). They can be regulated in
      bacteria, yeast, plants and animals to respond to stress conditions, resulting in
      regulation of gene expressions at both transcriptional and post-transcriptional
      level. Increasing evidence showed that the dysregulation of a series of tsncRNAs
      is associated with several types of human disease. In this review, we summarize
      the diversity and biogenesis of tsncRNAs in mammals and highlight the functions
      and mechanisms of different sub-classes of tsncRNAs in human disease.

PMID- 29337108
TI  - A vascular disrupting agent overcomes tumor multidrug resistance by skewing
      macrophage polarity toward the M1 phenotype.
AB  - Multidrug resistance (MDR) mediated by ATP-binding cassette (ABC) transporters is
      the major obstacle for chemotherapeutic success. Although attempts have been made
      to circumvent ABC transporter-mediated MDR in past decades, there is still no
      effective agent in clinic. Here, we identified a vascular disrupting agent, Z-GP
      DAVLBH, that significantly inhibited the growth of multidrug-resistant human
      hepatoma HepG2/ADM and human breast cancer MCF-7/ADR tumor xenografts, although
      these cells were insensitive to Z-GP-DAVLBH in vitro. Z-GP-DAVLBH increased the
      secretion of granulocyte-macrophage colony-stimulating factor in tumor tissues
      and serum of tumor-bearing mice to skew tumor-associated macrophages from the pro
      tumor M2 phenotype to the antitumor M1 phenotype, thereby contributing to the
      induction of HepG2/ADM and MCF-7/ADR cell apoptosis. Our findings shed new light
      on the underlying mechanisms of VDAs in the treatment of drug-resistant tumors
      and provide strong evidence that Z-GP-DAVLBH should be a promising agent for
      overcoming MDR.

PMID- 29337109
TI  - Molecular mechanisms of lncRNA SMARCC2/miR-551b-3p/TMPRSS4 axis in gastric
      cancer.
AB  - Decreased expression of miR-551b-3p has been identified in gastric cancer tissues
      but its biological role and underlying mechanism in this malignancy is poorly
      understood. In this study, we show that the expression of miR-551b-3p negatively
      correlates with the depth of tumour invasion and lymphatic metastasis, but it
      positively correlates with tumour differentiation and the patient survival. MiR
      551b-3p negatively affects the proliferation, mobility and invasiveness of
      gastric cancer cells. LncRNA SMARCC2 inhibits the expression of miR-551b-3p
      through binding to its mRNA response elements in gastric cancer cells.
      Overexpression of LncRNA SMARCC2 enhances the proliferation and migration of
      gastric cancer cells, while inhibition of LncRNA SMARCC2 does the opposite.
      TMPRSS4 is a direct target gene of miR-551b-3p. We conclude that miR-551b-3p
      functions as a tumour suppressor gene in gastric cancer, and its function is
      regulated by LncRNA SMARCC2/miR-551b-3p/TMPRSS4 axis.

PMID- 29337110
TI  - MUC16 C terminal-induced secretion of tumor-derived IL-6 contributes to tumor
      associated Treg enrichment in pancreatic cancer.
AB  - Pancreatic cancer is the most lethal tumor. CA125 (gene symbol MUC16) is an
      important serum marker for pancreatic cancer diagnosis and treatment. High serum
      CA125 is related to metabolic tumor burden and poor prognosis. The circulating
      Treg subset is another independent prognostic factor for pancreatic cancer. Our
      unpublished data indicated that the circulating Treg proportion might be related
      to the serum CA125 level. However, the potential relationship and underlying
      mechanism of MUC16 and Treg in pancreatic cancer tissues remain unclear. In this
      study, we found that pancreatic cancer tissues were positive for both MUC16 C
      terminal (MUC16c) and Foxp3 expression and that their expression was correlated.
      MUC16c released into the cytoplasm via EGF induction significantly increased IL-6
      expression and secretion. The PI3K/AKT pathway may participate in the regulation
      of IL-6 expression and secretion. By treating CD4+ T cells with IL-6 or co
      culturing the cells with pancreatic cancer cells, tumor-derived IL-6 was
      identified to promote Foxp3 expression and Treg differentiation, which was
      significantly inhibited by the JAK2 inhibitor AG-490. In sum, our study
      demonstrated that the relationship between the MUC16c level and Foxp3 expression
      in the local tumor environment was consistent with that of the serum CA125 level
      and circulating Treg proportion in the systemic environment. MUC16c promoted
      Foxp3 expression and tumor-associated Treg enrichment in tumor tissues through
      tumor-secreted IL-6 activation of the JAK2/STAT3 pathway. These findings may
      provide deeper insight into potential pancreatic cancer therapy approaches.

PMID- 29337111
TI  - Early re-staging and molecular subtype shift surveillance of locally recurrent or
      metastatic breast cancer: A new PET/CT integrated precise algorithm.
AB  - Recurrent breast cancer poses considerable diagnostic and therapeutic challenges
      for clinic. Clinical suspicion of recurrence must be first confirmed by imaging
      studies. Then re-biopsy of suspected recurrence and metastasis in patients with
      breast cancer is recommended in the practice guidelines of the National
      Comprehensive Cancer Network (NCCN) and European Society for Medical Oncology
      (ESMO) to confirm whether the molecular subtype changes. It may change the
      individual treatment plan directly. Our research provided an integrated algorithm
      for locally recurrent or distant metastatic breast cancer, including early
      relapse detection and subsequently a new practical PET/CT imaging guide biopsy
      approach for surveilling molecular subtype shifts of the recurrent breast cancer.
      In our results, 18F-FDG PET/CT appears to be more sensitive and accurate than
      conventional imaging technologies in early detecting locally recurrent or
      metastatic breast cancer. PET/CT-guided percutaneous FDG-avid target biopsies
      offers a new integrated precise re-biopsy algorithm for pathologic confirm and
      surveillance of molecular subtype shifts of the recurrent breast cancer. The
      precise algorithm for breast cancer recurrence and metastasis can be established
      in one stop, opening a window of opportunity for breast cancer patients to
      improve precise individual therapy and prolong survival.

PMID- 29337112
TI  - Molecular heterogeneity in diffuse large B-cell lymphoma and its implications in
      clinical diagnosis and treatment.
AB  - Over half of patients with diffuse large B-cell lymphoma (DLBCL) can be cured by
      standard R-CHOP treatment (rituximab, cyclophosphamide, doxorubicin, vincristine,
      and prednisone). However, the remaining patients are refractory and ultimately
      succumb to progressive or relapsed disease. During the past decade, there has
      been significant progress in the understanding of molecular mechanisms in DLBCL,
      largely owing to collaborative efforts in large-scale gene expression profiling
      and deep sequencing, which have identified genetic alterations critical in
      lymphomagenesis through activation of key signaling transduction pathways in
      DLBCL. These discoveries have not only led to the development of targeted
      therapies, including several currently in clinical trials, but also laid a solid
      foundation for the future identification of more effective therapies for patients
      not curable by R-CHOP. This review summarizes the recent advances in our
      understanding of the molecular characterization and pathogenesis of DLBCL and new
      treatment directions.

PMID- 29337113
TI  - Volta phase plate data collection facilitates image processing and cryo-EM
      structure determination.
AB  - A current bottleneck in structure determination of macromolecular complexes by
      cryo electron microscopy (cryo-EM) is the large amount of data needed to obtain
      high-resolution 3D reconstructions, including through sorting into different
      conformations and compositions with advanced image processing. Additionally, it
      may be difficult to visualize small ligands that bind in sub-stoichiometric
      levels. Volta phase plates (VPP) introduce a phase shift in the contrast transfer
      and drastically increase the contrast of the recorded low-dose cryo-EM images
      while preserving high frequency information. Here we present a comparative study
      to address the behavior of different data sets during image processing and
      quantify important parameters during structure refinement. The automated data
      collection was done from the same human ribosome sample either as a conventional
      defocus range dataset or with a Volta phase plate close to focus (cfVPP) or with
      a small defocus (dfVPP). The analysis of image processing parameters shows that
      dfVPP data behave more robustly during cryo-EM structure refinement because
      particle alignments, Euler angle assignments and 2D & 3D classifications behave
      more stably and converge faster. In particular, less particle images are required
      to reach the same resolution in the 3D reconstructions. Finally, we find that
      defocus range data collection is also applicable to VPP. This study shows that
      data processing and cryo-EM map interpretation, including atomic model
      refinement, are facilitated significantly by performing VPP cryo-EM, which will
      have an important impact on structural biology.

PMID- 29337114
TI  - Pathological Endogenous alpha-Synuclein Accumulation in Oligodendrocyte Precursor
      Cells Potentially Induces Inclusions in Multiple System Atrophy.
AB  - Glial cytoplasmic inclusions (GCIs), commonly observed as alpha-synuclein (alpha
      syn)-positive aggregates within oligodendrocytes, are the pathological hallmark
      of multiple system atrophy. The origin of alpha-syn in GCIs is uncertain; there
      is little evidence of endogenous alpha-syn expression in oligodendrocyte lineage
      cells, oligodendrocyte precursor cells (OPCs), and mature oligodendrocytes
      (OLGs). Here, based on in vitro analysis using primary rat cell cultures, we
      elucidated that preformed fibrils (PFFs) generated from recombinant human alpha
      syn trigger multimerization and an upsurge of endogenous alpha-syn in OPCs, which
      is attributable to insufficient autophagic proteolysis. RNA-seq analysis of OPCs
      revealed that alpha-syn PFFs interfered with the expression of proteins
      associated with neuromodulation and myelination. Furthermore, we detected
      cytoplasmic alpha-syn inclusions in OLGs through differentiation of OPCs pre
      incubated with PFFs. Overall, our findings suggest the possibility of endogenous
      alpha-syn accumulation in OPCs that contributes to GCI formation and perturbation
      of neuronal/glial support in multiple system atrophy brains.

PMID- 29337116
TI  - Impact of Swiprosin-1/Efhd2 on Adult Hippocampal Neurogenesis.
AB  - Swiprosin-1/Efhd2 (Efhd2) is highly expressed in the CNS during development and
      in the adult. EFHD2 is regulated by Ca2+ binding, stabilizes F-actin, and
      promotes neurite extension. Previous studies indicated a dysregulation of EFHD2
      in human Alzheimer's disease brains. We hypothesized a detrimental effect of
      genetic ablation of Efhd2 on hippocampal integrity and specifically investigated
      adult hippocampal neurogenesis. Efhd2 was expressed throughout adult neuronal
      development and in mature neurons. We observed a severe reduction of the survival
      of adult newborn neurons in Efhd2 knockouts, starting at the early neuroblast
      stage. Spine formation and dendrite growth of newborn neurons were compromised in
      full Efhd2 knockouts, but not upon cell-autonomous Efhd2 deletion. Together with
      our finding of severe hippocampal tauopathy in Efhd2 knockout mice, these data
      connect Efhd2 to impaired synaptic plasticity as present in Alzheimer's disease
      and identify a role of Efhd2 in neuronal survival and synaptic integration in the
      adult hippocampus.

PMID- 29337115
TI  - Purification of GFRalpha1+ and GFRalpha1- Spermatogonial Stem Cells Reveals a
      Niche-Dependent Mechanism for Fate Determination.
AB  - Undifferentiated spermatogonia comprise a pool of stem cells and progenitor cells
      that show heterogeneous expression of markers, including the cell surface
      receptor GFRalpha1. Technical challenges in isolation of GFRalpha1+ versus
      GFRalpha1- undifferentiated spermatogonia have precluded the comparative
      molecular characterization of these subpopulations and their functional
      evaluation as stem cells. Here, we develop a method to purify these
      subpopulations by fluorescence-activated cell sorting and show that GFRalpha1+
      and GFRalpha1- undifferentiated spermatogonia both demonstrate elevated
      transplantation activity, while differing principally in receptor tyrosine kinase
      signaling and cell cycle. We identify the cell surface molecule melanocyte cell
      adhesion molecule (MCAM) as differentially expressed in these populations and
      show that antibodies to MCAM allow isolation of highly enriched populations of
      GFRalpha1+ and GFRalpha1- spermatogonia from adult, wild-type mice. In germ cell
      culture, GFRalpha1- cells upregulate MCAM expression in response to glial cell
      line-derived neurotrophic factor (GDNF)/fibroblast growth factor (FGF)
      stimulation. In transplanted hosts, GFRalpha1- spermatogonia yield GFRalpha1+
      spermatogonia and restore spermatogenesis, albeit at lower rates than their
      GFRalpha1+ counterparts. Together, these data provide support for a model of a
      stem cell pool in which the GFRalpha1+ and GFRalpha1- cells are closely related
      but show key cell-intrinsic differences and can interconvert between the two
      states based, in part, on access to niche factors.

PMID- 29337117
TI  - XIST Derepression in Active X Chromosome Hinders Pig Somatic Cell Nuclear
      Transfer.
AB  - Pig cloning by somatic cell nuclear transfer (SCNT) remains extremely
      inefficient, and many cloned embryos undergo abnormal development. Here, by
      profiling transcriptome expression, we observed dysregulated chromosome-wide gene
      expression in every chromosome and identified a considerable number of genes that
      are aberrantly expressed in the abnormal cloned embryos. In particular, XIST, a
      long non-coding RNA gene, showed high ectopic expression in abnormal embryos. We
      also proved that nullification of the XIST gene in donor cells can normalize
      aberrant gene expression in cloned embryos and enhance long-term development
      capacity of the embryos. Furthermore, the increased quality of XIST-deficient
      embryos was associated with the global H3K9me3 reduction. Injection of H3K9me
      demethylase Kdm4A into NT embryos could improve the development of pre
      implantation stage embryos. However, Kdm4A addition also induced XIST
      derepression in the active X chromosome and thus was not able to enhance the in
      vivo long-term developmental capacity of porcine NT embryos.

PMID- 29337118
TI  - Recapitulation of Extracellular LAMININ Environment Maintains Stemness of
      Satellite Cells In Vitro.
AB  - Satellite cells function as precursor cells in mature skeletal muscle homeostasis
      and regeneration. In healthy tissue, these cells are maintained in a state of
      quiescence by a microenvironment formed by myofibers and basement membrane in
      which LAMININs (LMs) form a major component. In the present study, we evaluated
      the satellite cell microenvironment in vivo and found that these cells are
      encapsulated by LMalpha2-5. We sought to recapitulate this satellite cell niche
      in vitro by culturing satellite cells in the presence of recombinant LM-E8
      fragments. We show that treatment with LM-E8 promotes proliferation of satellite
      cells in an undifferentiated state, through reduced phosphorylation of JNK and
      p38. On transplantation into injured muscle tissue, satellite cells cultured with
      LM-E8 promoted the regeneration of skeletal muscle. These findings represent an
      efficient method of culturing satellite cells for use in transplantation through
      the recapitulation of the satellite cell niche using recombinant LM-E8 fragments.

PMID- 29337119
TI  - SOX10 Single Transcription Factor-Based Fast and Efficient Generation of
      Oligodendrocytes from Human Pluripotent Stem Cells.
AB  - Scarce access to primary samples and lack of efficient protocols to generate
      oligodendrocytes (OLs) from human pluripotent stem cells (hPSCs) are hampering
      our understanding of OL biology and the development of novel therapies. Here, we
      demonstrate that overexpression of the transcription factor SOX10 is sufficient
      to generate surface antigen O4-positive (O4+) and myelin basic protein-positive
      OLs from hPSCs in only 22 days, including from patients with multiple sclerosis
      or amyotrophic lateral sclerosis. The SOX10-induced O4+ population resembles
      primary human OLs at the transcriptome level and can myelinate neurons in vivo.
      Using in vitro OL-neuron co-cultures, myelination of neurons by OLs can also be
      demonstrated, which can be adapted to a high-throughput screening format to test
      the response of pro-myelinating drugs. In conclusion, we provide an approach to
      generate OLs in a very rapid and efficient manner, which can be used for disease
      modeling, drug discovery efforts, and potentially for therapeutic OL
      transplantation.

PMID- 29337121
TI  - The Society of Thoracic Surgeons Congenital Heart Surgery Database: 2018 Update
      on Outcomes and Quality.
AB  - The Society of Thoracic Surgeons Congenital Heart Surgery Database is a
      comprehensive registry of clinical outcomes that captures almost all pediatric
      cardiac surgical operations in the United States. It is the platform for all
      activities of The Society of Thoracic Surgeons related to the analysis of
      outcomes and the improvement of quality in this subspecialty. This article
      summarizes current aggregate national outcomes in congenital and pediatric
      cardiac surgery and reviews related activities in the areas of quality
      measurement, performance improvement, and transparency. The reported data about
      aggregate national outcomes are exemplified by an analysis of 10 benchmark
      operation groups performed from January 2013 through December 2016. This analysis
      documents the overall aggregate Operative Mortality (interquartile range among
      all participating programs) for the following procedural groups: off-bypass
      coarctation repair, 1.3% (0.0% to 1.4%%); ventricular septal defect repair, 0.6%
      (0.0% to 0.9%); tetralogy of Fallot repair, 1.1% (0.0% to 2.0%); complete
      atrioventricular canal repair, 2.7% (0.0% to 4.4%); arterial switch operation,
      2.2% (0.0% to 2.9%); arterial switch operation and ventricular septal defect
      repair, 5.1% (0.0% to 8.3%); Glenn/HemiFontan, 2.1% (0.0% to 3.1%); Fontan
      operation, 1.1% (0.0% to 0.0%); truncus arteriosus repair, 10.1% (0.0% to 15.4%);
      and Norwood procedure, 15.8% (9.0% to 25.0%).

PMID- 29337120
TI  - Deriving Dorsal Spinal Sensory Interneurons from Human Pluripotent Stem Cells.
AB  - Cellular replacement therapies for neurological conditions use human embryonic
      stem cell (hESC)- or induced pluripotent stem cell (hiPSC)-derived neurons to
      replace damaged or diseased populations of neurons. For the spinal cord,
      significant progress has been made generating the in-vitro-derived motor neurons
      required to restore coordinated movement. However, there is as yet no protocol to
      generate in-vitro-derived sensory interneurons (INs), which permit perception of
      the environment. Here, we report on the development of a directed differentiation
      protocol to derive sensory INs for both hESCs and hiPSCs. Two developmentally
      relevant factors, retinoic acid in combination with bone morphogenetic protein 4,
      can be used to generate three classes of sensory INs: the proprioceptive dI1s,
      the dI2s, and mechanosensory dI3s. Critical to this protocol is the competence
      state of the neural progenitors, which changes over time. This protocol will
      facilitate developing cellular replacement therapies to reestablish sensory
      connections in injured patients.

PMID- 29337122
TI  - Lung Focused Resuscitation at a Specialized Donor Care Facility Improves Lung
      Procurement Rates.
AB  - BACKGROUND: Lung procurement for transplantation occurs in approximately 20% of
      brain dead donors and is a major impediment to wider application of lung
      transplantation. We investigated the effect of lung protective management at a
      specialized donor care facility on lung procurement rates from brain dead donors.
      METHODS: Our local organ procurement organization instituted a protocol of lung
      protective management at a freestanding specialized donor care facility in 2008.
      Brain dead donors from 2001 to 2007 (early period) were compared with those from
      2009 to 2016 (current period) for lung procurement rates and other solid-organ
      procurement rates using a prospectively maintained database. RESULTS: An overall
      increase occurred in the number of brain dead donors during the study period
      (early group, 791; late group, 1,333; p < 0.0001). The lung procurement rate
      (lung donors/all brain dead donors) improved markedly after the introduction of
      lung protective management (early group, 157 of 791 [19.8%]; current group, 452
      of 1,333 [33.9%]; p < 0.0001). The overall organ procurement rate (total number
      of organs procured/donor) also increased during the study period (early group,
      3.5 organs/donor; current group, 3.8 organs/donor; p = 0.006). CONCLUSIONS: Lung
      protective management in brain dead donors at a specialized donor care facility
      is associated with higher lung utilization rates compared with conventional
      management. This strategy does not adversely affect the utilization of other
      organs in a multiorgan donor.

PMID- 29337123
TI  - Mesenchymal Stem Cell-Based Therapy Improves Lower Limb Movement After Spinal
      Cord Ischemia in Rats.
AB  - BACKGROUND: Spinal cord ischemia is a devastating complication after thoracic and
      thoracoabdominal aortic operations. In this study, we aimed to investigate the
      effects of mesenchymal stem cells (MSCs), which have regenerative capability and
      exert paracrine actions on damaged tissues, injected into rat models of spinal
      cord ischemia-reperfusion injury. METHODS: Forty-five Sprague-Dawley rats were
      divided into sham, phosphate-buffered saline (PBS), and MSC groups. Spinal cord
      ischemia was induced in the latter two groups by balloon occlusion of the
      thoracic aorta. MSCs and PBS were then immediately injected into the left carotid
      artery of the MSC and PBS groups, respectively. Hindlimb motor function was
      evaluated at 6 and 24 hours. The spinal cord was removed at 24 hours after
      ischemia-reperfusion injury, and histologic and immunohistochemical analyses and
      real-time polymerase chain reaction assessments were performed. RESULTS: Rats in
      the MSC and PBS groups showed flaccid paraparesis/paraplegia postoperatively.
      Hindlimb function was significantly better at 6 and 24 hours after ischemia
      reperfusion injury in the MSC group than in the PBS group (p < 0.05). The number
      of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive neuron
      cells in the spinal cord and the ratio of Bax to Bcl2 were significantly larger
      (p < 0.05) in the PBS group than in the MSC group. The injected MSCs were
      observed in the spinal cord 24 hours after ischemia-reperfusion injury.
      CONCLUSIONS: The MSC therapy by transarterial injection immediately after spinal
      cord ischemia-reperfusion injury may improve lower limb function by preventing
      apoptosis of neuron cells in the spinal cord.

PMID- 29337124
TI  - Evaluation of Prophylactic Antibiotic Use for Delayed Sternal Closure After
      Cardiothoracic Operation.
AB  - BACKGROUND: Clinical practice guidelines provide recommendations for surgical
      prophylaxis in patients undergoing cardiothoracic procedures. However, currently
      no recommendations guide the management of antibiotic prophylaxis in patients who
      require delayed sternal closure after cardiothoracic operation. METHODS: This is
      a single-center, retrospective analysis. Data were extracted from The Society of
      Thoracic Surgery database and electronic medical record from July 2011 through
      January 2016. Patients included are adults (>=18 years old) after cardiothoracic
      operation with delayed sternal closure. RESULTS: A total of 167 patients were
      included for analysis. The majority of patients (131, 78.4%) were continued on
      routine antibiotics and 36 patients (21.6%) were switched to broad-spectrum
      antibiotics for prophylaxis. Of patients on routine antibiotic prophylaxis, 6
      (4.6%) experienced a sternal surgical site infection, whereas 3 patients (8.3%)
      switched to broad-spectrum agents before chest closure experienced a sternal
      surgical site infection (p = 0.407). Eleven patients (6.6%) received an
      abbreviated duration of antibiotics, 52 patients (31.1%) were continued on
      antibiotics until the time of sternal closure, and 104 patients (62.3%) were
      continued on antibiotics past the time of sternal closure. The incidence of
      infection based on duration of prophylactic antibiotic was 0, 1 (1.9%), and 8
      (7.7%), respectively (p = 0.352). CONCLUSIONS: Substantial variation was found in
      the duration and selection of antibiotic prophylaxis for patients with delayed
      sternal closure after cardiothoracic operation. Broad-spectrum antimicrobial
      agents and extended durations of antibiotic prophylaxis were not associated with
      benefits in the incidence of sternal wound infection and may increase the risk of
      adverse effects.

PMID- 29337125
TI  - Facilitating Hemostasis After Proximal Aortic Surgery: Results of The PROTECT
      Trial.
AB  - BACKGROUND: This study intended to evaluate the safety and hemostatic efficacy of
      a novel vascular sealant (Tridyne; Neomend, Inc, Irvine, CA) compared with an
      accepted adjunctive hemostatic agent applied to aortotomy and sutures lines in
      cardiovascular operations. METHODS: Patients undergoing aortic valve replacement,
      ascending aortic replacement, or aortic root replacement were randomly assigned
      2:1 to Tridyne (n = 107) or Gelfoam Plus (Baxter Healthcare Corp, Hayward, CA) (n
      = 51). These groups were similar with regard to age, sex, race, medical history,
      duration of bypass and cross-clamping, and number of suture lines treated. Suture
      lines were treated after confirmation of some leakage but before formal removal
      of the clamp. RESULTS: The median bleeding time was significantly lower for
      Tridyne versus Gelfoam Plus (0 versus 10.0 minutes, p < 0.0001). Immediate
      hemostasis was achieved in 59.4% of the Tridyne group versus 16.0% of Gelfoam
      Plus group (p < 0.0001). A significantly greater proportion of patients in the
      Tridyne group achieved successful hemostasis at the aortic suture line than
      patients in the Gelfoam Plus group (85.7% versus 40.0%, p < 0.0001). The Clinical
      Events Committee adjudicated 7 patients with possible device-related serious
      adverse events: 3 patients (2.9%) in the Tridyne group and 4 patients (8.2%) in
      the Gelfoam Plus group (p = 0.2097). CONCLUSIONS: Tridyne was safe and effective
      when used as an adjunct to conventional hemostasis to treat high-pressure vessels
      in patients who receive anticoagulation agents, in reducing time to hemostasis,
      and in promoting both immediate and persistent hemostasis.

PMID- 29337126
TI  - Rigid Plate Fixation Versus Wire Cerclage: Patient-Reported and Economic Outcomes
      From a Randomized Trial.
AB  - BACKGROUND: In a multicenter randomized trial, sternal closure after cardiac
      operations using rigid plate fixation (RPF) compared with wire cerclage (WC)
      resulted in improved sternal healing, reduced sternal complications, and was cost
      neutral at 6 months. Additional secondary end points are presented from this
      trial. METHODS: Twelve United States centers randomized 236 patients to RPF (n =
      116) or WC (n = 120). Patient-reported outcomes measures, including pain,
      function, and quality of life scores, were assessed through 6 months and
      correlated to computed tomography-derived sternal healing scores using logistic
      regression. Cost analysis through 90 days was performed to mimic bundled care
      models. RESULTS: All patient-reported outcomes measures were numerically better
      in RPF patients than in WC patients at all assessments. RPF resulted in more
      patients reporting no sternal pain after coughing at 3 weeks (41.1% vs 19.6%; p =
      0.001) and 6 weeks (54.5% vs 35.1%; p = 0.005) and at rest at 6 weeks (74.1% vs
      58.8%; p = 0.02) and 3 months (87.6% vs 75.9%; p = 0.03) compared with WC. Better
      sternal healing scores correlated to having no sternal pain at rest (odds ratio,
      1.6; 95% confidence interval, 1.2 to 2.2; p = 0.002) and after coughing (odds
      ratio, 1.6; 95% confidence interval, 1.2 to 2.2; p = 0.0007). RPF resulted in
      improvements in the 36-Item Short Form Health Survey quality of life scores at 3
      weeks (53.5 +/- 8.7 vs 50.5 +/- 10.4; p = 0.03), 6 weeks (45.3 +/- 8.4 vs 42.7 +/
      8.4; p = 0.03), and 6 months (56.4 +/- 6.8 vs 53.9 +/- 9.0; p = 0.04) compared
      with WC. Through 90 days, RPF compared with WC was $1,888 less (95% confidence
      interval, -$8,889 to $4,273; p = 0.52). CONCLUSIONS: In patients undergoing
      sternal closure after median sternotomy, RPF compared with WC resulted in reduced
      sternal pain, improved upper extremity function, and similar total 90-day costs.

PMID- 29337127
TI  - [Epidemiology of emergency consultations for acute urine retention].
AB  - INTRODUCTION: Acute urinary retention (AUR) is a common reason for emergency
      consultation. It may be spontaneous or precipitated and affects both men and
      women. The purpose of this study was to determine the profile of men visiting
      emergency departments for an AUR. MATERIEL AND METHODS: A retrospective
      monocentric study including all men who consulted the emergency department
      between January 2014 and December 2016 for AUR was conducted. RESULTS: In 3
      years, 731 patients were admitted for AUR (611 men and 120 women). The mean age
      was 71.6+/-14 years with a mean retention volume of 948+/-668mL drained for 96%
      of patients (n=584) through a bladder catheter and 4% (n=27) with a suprapubic
      catheter. Most patients had an urological (66%, n=104) or neurologic (40%, n=242)
      history and 23% (n=136) already had an episode of AUR. In 28% of cases (n=173),
      the globe was not painful. A majority of AUR were spontaneous, 53% (n=326) versus
      46% (n=279) who were precipitated, secondary to a recent surgical procedure (<1
      month) (15%, n=89), hematuria (9%, n=54), or male urinary tract infections (7%,
      n=42). Patients were treated externally in 71% (n=436), 25% (n=153) were
      hospitalized with significantly more comorbidities. CONCLUSION: Men consulting
      emergency for AUR are 72 years old, with a globe volume of 942mL. Thirty-three
      percent have a history of BPH, with a prostate treatment like alpha-blockers
      type. Almost all patients were treated with a bladder catheter and the majority
      was treated externally. LEVEL OF EVIDENCE: 4.

PMID- 29337128
TI  - [Estimating minimum period of time to perform prostate MRI after prostate biopsy:
      Clinical and histological bleeding risk factors; from a prospective study].
AB  - : A minimum delay of 4 to 6 weeks between biopsy and multiparametric prostatic
      MRI (mpMRI) is admitted due to post-biopsy hemorrhage that can impact MRI reading
      without strong scientific evidence. The objective of the study was to evaluate
      the best period between prostate biopsy and 3Tesla mpMRI and searching for
      predictive factors of intraprostatic blood. METHOD: A prostate biopsy followed by
      a 4-week prostate MRI (MRIp M1) was performed. In case of hemorrhage, MRI was
      rescheduled at 8 and 12 weeks (M2/M3). We analyzed the persistant bleeding to
      identify risk factors: anticoagulant/antiaggregant, post-biopsy side effects,
      histological criteria. RESULTS: In this prospective, single-center study, we
      included 40 patients followed for suspected prostate cancer between December 2014
      and March 2016. At the MRIpM1, blood was found for 97.5 % of the patients. The
      rates were 90.9 % and 88.9 % respectively at the M2 and M3 mpMRI. Compared to
      initial blood volume on MRIpM1, a significant decrease in blood volume was
      observed between M1 and M2 (55 %; P=0.0091). We showed a 75 % decrease between M1
      and M3 (P=0.0003). Low urinary tract symptoms (LUTS) suggesting urinary infection
      at 4 weeks were significantly correlated with blood volume on MRIpM1 (P=0.0063).
      The blood volume was higher in case of unconformity between biopsy and mpMRI
      results for detection of significant tumors (11.3 vs. 2.3; P=0.0051).
      CONCLUSIONS: A minimum of 8-week biopsy and mpMRI period would limit post-biopsy
      hemorrhage, predicted by LUTS suggesting urinary infection. A delay of 12 weeks
      would be optimal without delaying the management of the patient. LEVEL OF
      EVIDENCE: 4.

PMID- 29337129
TI  - Effect of amino acid substitution of CAPRICE on cell-to-cell movement ability in
      Arabidopsis root epidermis.
AB  - An R3-type MYB transcription factor, CAPRICE (CPC), is known to promote root hair
      cell differentiation in Arabidopsis root epidermis. The CPC protein moves from
      non-hair cells to the neighboring cells, and acts as an inducer of root hair
      formation. In contrast, we previously showed that the CPC homolog, ENHANCER OF
      TRY AND CPC1 (ETC1), does not move between the root epidermal cells. To clarify
      the critical difference in the cell-to-cell movement ability of CPC and ETC1
      proteins, we generated five different chimeras of CPC and ETC1. As expected, four
      of the five chimeric proteins with substitution of CPC amino acids with those of
      ETC1 induced many root hair and no-trichome phenotype, like CPC. These chimeric
      proteins essentially maintained the cell-to-cell movement ability of CPC.
      However, one chimeric protein in which ETC1 was sandwiched between the CPC
      specific movement motifs of S1 and S2 did not induce ectopic root hair formation.
      This chimeric protein did not move between the cells. These results indicate that
      the maintenance of not only the S1 and S2 motifs but also the precise structure
      of CPC protein might be necessary for the cell-to-cell movement of CPC. Our
      results should help in further unraveling of the roles of these MYB transcription
      factors in root hair formation.

PMID- 29337130
TI  - An organizing role for the TGF-beta signaling pathway in axes formation of the
      annelid Capitella teleta.
AB  - Embryonic organizers are signaling centers that coordinate developmental events
      within an embryo. Localized to either an individual cell or group of cells,
      embryonic organizing activity induces the specification of other cells in the
      embryo and can influence formation of body axes. In the spiralian Capitella
      teleta, previous cell deletion studies have shown that organizing activity is
      localized to a single cell, 2d, and this cell induces the formation of the dorsal
      ventral axis and bilateral symmetry. In this study, we attempt to identify the
      signaling pathway responsible for the organizing activity of 2d. Embryos at
      stages when organizing activity is occurring were exposed to various small
      molecule inhibitors that selectively inhibited either the Activin/Nodal or the
      BMP branch of the TGF-beta signaling pathway. Embryos were then raised to larval
      stages, and scored for axial anomalies analogous to 2d ablated phenotypes. Our
      results show that interference with the Activin/Nodal pathway through a short
      three hour exposure to the inhibitor SB431542 results in larvae that lack
      bilateral symmetry and a detectable dorsal-ventral axis. However, interference
      with the BMP signaling pathway through exposure to the inhibitors DMH1 and
      dorsomorphin dihydrochloride does not appear to play a role in specification by
      2d of the dorsal-ventral axis or bilateral symmetry. Our findings highlight
      species differences in how the molecular architecture of the conserved TGF-beta
      superfamily signaling pathway components was utilized to mediate the organizing
      activity signal during early spiralian development.

PMID- 29337131
TI  - Modelling non-Markovian fluctuations in intracellular biomolecular transport.
AB  - To model non-Markovian fluctuations arising in biomolecular transport, we
      introduce a stochastic process with memory where Brownian motion is modulated
      sinusoidally. The probability density function and moments of this non-Markovian
      process are evaluated analytically as Hida stochastic functional integrals.
      Comparison of graphs of computed variance vis-a-vis empirical data for protein
      diffusion coefficients closely match with both exhibiting emergent superdiffusive
      then subdiffusive behavior for longer proteins.

PMID- 29337132
TI  - Understanding pivotal experiences in behavior change for the design of
      technologies for personal wellbeing.
AB  - Most health technologies are designed to support people who have already decided
      to work toward better health. Thus, there remains an opportunity to design
      technologies to help motivate people who have not yet decided to make a change.
      Understanding the experiences of people who have already started to make a health
      behavior change and how they made a pivotal decision can be useful in
      understanding how to design such tools. In this paper, we describe results from
      data collected in 2 phases. Phase 1 consisted of 127 surveys and 13 interviews
      with adults who have already accomplished behavior change(s). Phase 2 consisted
      of 117 surveys and 12 interviews with adults who have either already accomplished
      their behavior change(s) or are currently working toward them. We identified four
      factors that lead to pivotal experiences: (1) prolonged discontent and desire to
      change, (2) significant changes that increase fear or hope of future, (3)
      increased understanding of one's behavior and personal data, and (4) social
      accountability. We also describe a design space for designing technology-based
      interventions for encouraging people to decide to make a change to improve their
      health. Based on feedback from participants, we discuss opportunities for further
      exploration of the design space for people who are not yet motivated to change
      and for ethical considerations for this type of intervention.

PMID- 29337133
TI  - Cathodal tDCS of the bilateral anterior temporal lobes facilitates semantically
      driven verbal fluency.
AB  - In a verbal fluency task, a person is required to produce as many exemplars of a
      given category (e.g., 'animals', or words starting with 'f') as possible within a
      fixed duration. Successful verbal fluency performance relies both on the depth of
      search within semantic/phonological neighborhoods ('clustering') and the ability
      to flexibly disengage between exhausted clusters ('switching'). Convergent
      evidence from functional imaging and neuropsychology suggests that cluster-switch
      behaviors engage dissociable brain regions. Switching has been linked to a
      frontoparietal network dedicated to executive functioning and controlled lexical
      retrieval, whereas clustering is more commonly associated with temporal lobe
      regions dedicated to semantic and phonological processing. Here we attempted to
      modulate cluster-switch dynamics among neurotypical adults (N = 24) using
      transcranial direct current stimulation (tDCS) delivered at three sites: a)
      anterior temporal cortex; b) frontal cortex; and c) temporoparietal cortex.
      Participants completed letter-guided and semantic category verbal fluency tasks
      pre/post stimulation. Cathodal stimulation of anterior temporal cortex
      facilitated the total number of words generated and the number of words generated
      within clusters during semantic category verbal fluency. These neuromodulatory
      effects were specific to stimulation of the one anatomical site. Our findings
      highlight the role of the anterior temporal lobes in representing semantic
      category structure and support the claim that clustering and switching behaviors
      have distinct substrates. We discuss implications both for theory and application
      to neurorehabilitation.

PMID- 29337134
TI  - Acetylcholine Receptor Antibody Titers and Clinical Course after Influenza
      Vaccination in Patients with Myasthenia Gravis: A Double-Blind Randomized
      Controlled Trial (ProPATIent-Trial).
AB  - BACKGROUND: It is a continuous matter of discussion whether immune activation by
      vaccination in general and Influenza vaccination in particular increases the risk
      for clinical deterioration of autoimmune diseases. This prospective study
      investigated the serological and clinical course of autoimmune Myasthenia gravis
      (MG) after a seasonal influenza vaccination. METHODS: This randomized, placebo
      controlled, double-blind study enrolled MG patients with antibodies against
      acetylcholine-receptors (AChR-ab). They were allocated to receive seasonal
      influenza vaccine or placebo. The primary endpoint was the relative change of
      AChR-ab-titer over 12weeks. A relative increase of 20% was set as non-inferiority
      margin. Secondary endpoints were clinical changes in the modified Quantitative
      Myasthenia Gravis Score (QMG), increase of anti-influenza-ELISA-antibodies, and
      changes of treatment. The study is registered with Clinicaltrialsregister.eu,
      EudraCT number 2006-004374-27. FINDINGS: 62 patients were included. Mean+/
      standard deviation (median) in the vaccine and placebo group were AChR-ab-titer
      changes of -6.0%+/-23.3% (-4.0%) and -2.8%+/-22.0% (-0.5%) and QMG score changes
      of -0.08+/-0.27 (0.17) and 0.11+/-0.31 (0.00), respectively. The difference
      between groups (Hodges-Lehmann estimate with 95% CI) was - for the AChR-ab-titer
      change 4.0% [-13.3%, 4.5%] (p=0.28 for testing a difference, p<0.0001 for testing
      non-inferiority) and for the QMG change 0.00 [-0.17, 0.00] (p=0.79 for testing a
      difference). The occurrence of 74 adverse events (AE) was comparable between
      groups. The most common AE was flu-like symptoms. One serious AE (hospitalisation
      following gastrointestinal haemorrhage) in the verum group was not related to the
      vaccine. INTERPRETATION: Influenza vaccination in MG is safe. Uprating the
      potential risk of a severe course of MG exacerbation during influenza infection
      compared to the 95% CI differences for the endpoints, vaccination is principally
      indicated in this patient population.

PMID- 29337135
TI  - Defining Bedaquiline Susceptibility, Resistance, Cross-Resistance and Associated
      Genetic Determinants: A Retrospective Cohort Study.
AB  - BACKGROUND: Bedaquiline (BDQ) is a novel agent approved for use in combination
      treatment of multi-drug resistant tuberculosis (MDR-TB). We sought to determine
      BDQ epidemiological cut-off values (ECVs), define and assess interpretive
      criteria against putative resistance associated variants (RAVs), microbiological
      outcomes and cross resistance with clofazimine (CFZ). METHODS: A retrospective
      cohort study was conducted. Minimal inhibitory concentrations (MIC) to BDQ were
      determined using 7H9 broth microdilution (BMD) and MGIT960. RAVs were genetically
      characterised using whole genome sequencing. BDQ ECVs were determined using
      ECOFFinder and compared with 6-month culture conversion status and CFZ MICs.
      FINDINGS: A total of 391 isolates were analysed. Susceptible and intermediate
      categories were determined to have MICs of <=0.125MUg/ml and 0.25MUg/ml using BMD
      and <=1MUg/ml and 2MUg/ml using MGIT960 respectively. Microbiological failures
      occurred among BDQ exposed patients with a non-susceptible BDQ MIC, an Rv0678
      mutation and <=2 active drug classes. The Rv0678 RAVs were not the dominant
      mechanism of CFZ resistance and cross resistance was limited to isolates with an
      Rv0678 mutation. INTERPRETATION: Criteria for BDQ susceptibility are defined and
      will facilitate improved early detection of resistance. Cross- resistance between
      BDQ and CFZ is an emerging concern but in this study was primarily among those
      with an Rv0678 mutation.

PMID- 29337136
TI  - As Extracellular Glutamine Levels Decline, Asparagine Becomes an Essential Amino
      Acid.
AB  - When mammalian cells are deprived of glutamine, exogenous asparagine rescues cell
      survival and growth. Here we report that this rescue results from use of
      asparagine in protein synthesis. All mammalian cell lines tested lacked cytosolic
      asparaginase activity and could not utilize asparagine to produce other amino
      acids or biosynthetic intermediates. Instead, most glutamine-deprived cell lines
      are capable of sufficient glutamine synthesis to maintain essential amino acid
      uptake and production of glutamine-dependent biosynthetic precursors, with the
      exception of asparagine. While experimental introduction of cytosolic
      asparaginase could enhance the synthesis of glutamine and increase tricarboxylic
      acid cycle anaplerosis and the synthesis of nucleotide precursors, cytosolic
      asparaginase suppressed the growth and survival of cells in glutamine-depleted
      medium in vitro and severely compromised the in vivo growth of tumor xenografts.
      These results suggest that the lack of asparaginase activity represents an
      evolutionary adaptation to allow mammalian cells to survive pathophysiologic
      variations in extracellular glutamine.

PMID- 29337138
TI  - Let-7 Suppresses B Cell Activation through Restricting the Availability of
      Necessary Nutrients.
AB  - The control of uptake and utilization of necessary extracellular nutrients
      glucose and glutamine-is an important aspect of B cell activation. Let-7 is a
      family of microRNAs known to be involved in metabolic control. Here, we employed
      several engineered mouse models, including B cell-specific overexpression of
      Lin28a or the let-7a-1/let-7d/let-7f-1 cluster (let-7adf) and knockout of
      individual let-7 clusters to show that let-7adf specifically inhibits T cell
      independent (TI) antigen-induced immunoglobulin (Ig)M antibody production. Both
      overexpression and deletion of let-7 in this cluster leads to altered TI-IgM
      production. Mechanistically, let-7adf suppresses the acquisition and utilization
      of key nutrients, including glucose and glutamine, through directly targeting
      hexokinase 2 (Hk2) and by repressing a glutamine transporter Slc1a5 and a key
      degradation enzyme, glutaminase (Gls), a mechanism mediated by regulation of c
      Myc. Our results suggest a novel role of let-7adf as a "metabolic brake" on B
      cell antibody production.

PMID- 29337137
TI  - Basal Mitophagy Occurs Independently of PINK1 in Mouse Tissues of High Metabolic
      Demand.
AB  - Dysregulated mitophagy has been linked to Parkinson's disease (PD) due to the
      role of PTEN-induced kinase 1 (PINK1) in mediating depolarization-induced
      mitophagy in vitro. Elegant mouse reporters have revealed the pervasive nature of
      basal mitophagy in vivo, yet the role of PINK1 and tissue metabolic context
      remains unknown. Using mito-QC, we investigated the contribution of PINK1 to
      mitophagy in metabolically active tissues. We observed a high degree of mitophagy
      in neural cells, including PD-relevant mesencephalic dopaminergic neurons and
      microglia. In all tissues apart from pancreatic islets, loss of Pink1 did not
      influence basal mitophagy, despite disrupting depolarization-induced Parkin
      activation. Our findings provide the first in vivo evidence that PINK1 is
      detectable at basal levels and that basal mammalian mitophagy occurs
      independently of PINK1. This suggests multiple, yet-to-be-discovered pathways
      orchestrating mammalian mitochondrial integrity in a context-dependent fashion,
      and this has profound implications for our molecular understanding of vertebrate
      mitophagy.

PMID- 29337139
TI  - Identification of yellow gene family in Agrotis ipsilon and functional analysis
      of Aiyellow-y by CRISPR/Cas9.
AB  - The yellow gene family has been identified in several model insects, but yellow
      genes were poorly identified in non-model insects and the functions of yellow
      genes are largely unknown. In this study, we identified seven yellow genes in an
      important agricultural pest Agrotis ipsilon. Each gene encodes a protein
      containing a major royal jelly domain. Phylogenetic analysis defined these genes
      as yellow-y, -b, -b2, -c, -d, -e, and -h, respectively. The A. ipsilon yellow
      genes yellow-b, -b2, and -c were stably expressed in all developmental stages and
      tissues analyzed, whereas the other four yellow genes had unique expression
      patterns, suggesting distinct physiological roles of each gene. Using the
      CRISPR/Cas9 system, we successfully disrupted yellow-y in A. ipsilon and obtained
      G0 insects with somatic mutations. Unlike the black of wild-type newly hatched
      larvae and of adults, the mutants were yellow, although in the pupal stage mutant
      coloration did not differ from wild-type coloration. This phenotype was inherited
      by G1 offspring. The G0 mutants did not show any growth deficiency compared with
      control insects; however, a dehydration-like phenotype was observed in newly
      hatched G1 larvae from sibling crossed mutants. Our results indicate that A.
      ipsilon yellow-y gene plays a role in body pigmentation and also might function
      in waterproofing.

PMID- 29337140
TI  - Characteristics and Prognostic Factors for Patients With HER2-overexpressing
      Breast Cancer and Brain Metastases in the Era of HER2-targeted Therapy: An
      Argument for Earlier Detection.
AB  - BACKGROUND: Although brain metastases (BM) are associated with poor prognosis,
      patients with human epidermal growth factor receptor 2 (HER2) overexpressing
      (HER2+) breast cancer (BC) with BM who are treated with anti-HER2 therapy have a
      relatively longer survival after BM diagnosis compared with other subtypes and
      HER2+ patients previously untreated with anti-HER2 therapy. It is unclear if
      previously reported prognostic factors are applicable to patients with HER2+ BC
      in the era of HER2-targeted therapy. PATIENTS AND METHODS: We evaluated 100
      consecutive patients with HER2+ BC with BM who underwent radiation therapy as
      primary BM treatment from January 2001 to December 2011 at Memorial Sloan
      Kettering Cancer Center by retrospective review. Patient characteristics at the
      time of BM diagnosis and their associations with time from BM to death were
      evaluated by Kaplan-Meier curves, log-rank tests, and Cox proportional hazard
      models. RESULTS: Significantly better survival from BM was noted for patients
      with higher performance status, fewer BM lesions, continued use of HER2-targeted
      therapy after BM diagnosis, and better controlled extracranial metastatic
      disease. Absence of neurologic symptoms at BM diagnosis was significantly
      associated with fewer lesions, decreased use of whole brain radiotherapy, and
      longer survival in univariate and multivariate analysis (multivariate hazard
      ratio, 3.69; 95% confidence interval, 1.69-8.07). CONCLUSION: Our finding
      supports the continued use of HER2-targeted therapy after BM diagnosis. In
      addition, future research on the clinical impact of detecting asymptomatic BM in
      patients with HER2+ BC, in terms of improving prognosis, quality of life, and
      avoidance of whole brain radiotherapy, is warranted.

PMID- 29337141
TI  - Alterations of oxygen consumption and extracellular acidification rates by
      glutamine in PBMCs of SLE patients.
AB  - We evaluated plasma glutamine levels and basal mitochondrial oxygen consumption
      rate (mOCRB) and basal extracellular acidification rate (ECARB) of peripheral
      blood mononuclear cells (PBMCs) of systemic lupus erythematous (SLE) patients and
      healthy controls (HCs). Lower plasma glutamine levels correlated with higher SLE
      disease activity indexes (p=0.025). Incubated in DMEM containing 100mg/dL
      glucose, SLE-PBMCs displayed lower mOCRB (p=0.018) but similar ECARB (p=0.467) to
      those of HC-PBMCs, and their mOCRB got elevated (p<0.001) without altering ECARB
      (p=0.239) by supplementation with 2 or 4mM glutamine. We conclude that impaired
      mitochondrial respiration of SLE-PBMCs could be improved by glutamine under
      euglycemic condition.

PMID- 29337143
TI  - The role of Hedgehog-responsive fibroblasts in facial nerve regeneration.
AB  - BACKGROUND: Facial nerve paralysis is a significant cause of morbidity, affecting
      facial appearance, emotional expression, speech, oral competence, and vision. A
      more complete understanding of the complex cellular events required for
      successful nerve regeneration may reveal new therapeutic targets. The role of
      fibroblasts in regeneration, and the process by which the nerve reforms its three
      dimensional structure after a transection injury, are not fully understood. The
      Hedgehog signaling pathway has been shown to mediate nerve sheath formation
      during development. We therefore sought to characterize the role of Hedgehog
      responsive cells following transection of the facial nerve. METHODS: Two
      transgenic mouse lines with reporters for the downstream effector of Hedgehog
      signaling, Gli1, were used. The animals underwent a unilateral facial nerve
      transection injury, and the contralateral side served as a control. Facial nerves
      were analyzed via immunohistochemistry and immunofluorescence at predetermined
      time points as the facial nerve regenerated after the transection injury.
      RESULTS: There was a statistically significant increase in Gli1+ cells both at
      the site of injury and within the distal nerve segment over time. Gli1+ cells are
      fibroblasts within the nerve and appear to contribute to the reformation of the
      nerve sheath after injury. CONCLUSION: These findings describe a key signaling
      pathway by which fibroblasts participate in motor nerve regeneration. Fibroblasts
      that reside within the nerve respond to injury and may represent a novel
      therapeutic target in the context of facial nerve regeneration after transection
      injury.

PMID- 29337144
TI  - Early activation of Egr-1 promotes neuroinflammation and dopaminergic
      neurodegeneration in an experimental model of Parkinson's disease.
AB  - The progressive loss of dopaminergic neurons in the substantia nigra pars
      compacta (SNpc) is one of the hallmarks of Parkinson's disease (PD).
      Neuroinflammation has been proposed to contributes to the progressive nature of
      the disease. Early growth response-1 (Egr-1), a zinc finger transcription factor,
      has been shown to have a crucial role in both neuronal death and the inflammatory
      response. However, whether and how Egr-1 is involved in the pathogenesis of PD
      has not been investigated. Using the subacute 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP) mouse model of PD, we identified early peak induction
      of Egr-1 in the SNpc but not in the striatum. In situ immunofluorescent analysis
      showed that Egr-1 predominantly locates in the nuclei of nigral AldoC (+)
      astrocytes upon MPTP treatment. Genetic ablation of Egr-1 or inhibition of its
      transcriptional activity by Mithramycin A significantly suppresses the activation
      of both astrocytes and microglia, decreases proinflammatory cytokine expression,
      and protects dopaminergic cell bodies from degeneration in the SNpc. Taken
      together, these findings demonstrate that the induction of Egr-1 promotes
      neuroinflammation and dopaminergic cell body loss in the SNpc of MPTP-induced
      mouse model, suggesting an important role of astrocytic Egr-1 in
      neuroinflammation in PD.

PMID- 29337142
TI  - Express: A database of transcriptome profiles encompassing known and novel
      transcripts across multiple development stages in eye tissues.
AB  - Advances in sequencing have facilitated nucleotide-resolution genome-wide
      transcriptomic profiles across multiple mouse eye tissues. However, these RNA
      sequencing (RNA-seq) based eye developmental transcriptomes are not organized for
      easy public access, making any further analysis challenging. Here, we present a
      new database "Express" (http://www.iupui.edu/~sysbio/express/) that unifies
      various mouse lens and retina RNA-seq data and provides user-friendly
      visualization of the transcriptome to facilitate gene discovery in the eye. We
      obtained RNA-seq data encompassing 7 developmental stages of lens in addition to
      that on isolated lens epithelial and fibers, as well as on 11 developmental
      stages of retina/isolated retinal rod photoreceptor cells from publicly available
      wild-type mouse datasets. These datasets were pre-processed, aligned, quantified
      and normalized for expression levels of known and novel transcripts using a
      unified expression quantification framework. Express provides heatmap and browser
      view allowing easy navigation of the genomic organization of transcripts or gene
      loci. Further, it allows users to search candidate genes and export both the
      visualizations and the embedded data to facilitate downstream analysis. We
      identified total of >81,000 transcripts in the lens and >178,000 transcripts in
      the retina across all the included developmental stages. This analysis revealed
      that a significant number of the retina-expressed transcripts are novel.
      Expression of several transcripts in the lens and retina across multiple
      developmental stages was independently validated by RT-qPCR for established genes
      such as Pax6 and Lhx2 as well as for new candidates such as Elavl4, Rbm5, Pabpc1,
      Tia1 and Tubb2b. Thus, Express serves as an effective portal for analyzing pruned
      RNA-seq expression datasets presently collected for the lens and retina. It will
      allow a wild-type context for the detailed analysis of targeted gene-knockout
      mouse ocular defect models and facilitate the prioritization of candidate genes
      from Exome-seq data of eye disease patients.

PMID- 29337145
TI  - Interaction of DCF1 with ATP1B1 induces impairment in astrocyte structural
      plasticity via the P38 signaling pathway.
AB  - Astrocytes are known to regulate and support neuronal and synaptic functions.
      Changes in their size and morphology in mouse models result in mental
      retardation. However, the mechanism underlying these morphological changes
      remains unclear. In the present study, abnormal astrocyte morphology was found in
      the mouse brain following knockout of dendritic cell factor 1 (Dcf1).
      Immunoprecipitation-mass spectrometry (IP-Mass) identified that ATP1B1 is bound
      to DCF1, and co-immunoprecipitation and cell fluorescence further confirmed an
      interaction between these two proteins, with asparagine residue 266 of ATP1B1
      being required for the interaction with DCF1. Moreover, Dcf1 knockout in mice
      resulted in upregulation of ATP1B1 expression in the hippocampus. Furthermore,
      DCF1 interaction with ATP1B1 in astrocytes impaired their structural plasticity.
      Ultimately, Dcf1 knockout increased glutamate release. Mechanism exploration
      proposed that Dcf1 knockout led to significantly perturbed expression of AMPA
      receptors (AMPARs) and induced morphological changes in astrocytes through the
      P38 signaling pathway. Our data shed light on the possible mechanisms underlying
      changes in astrocyte morphology and provide new avenues for the exploration of
      proteins involved in glutamate release.

PMID- 29337146
TI  - Apelin-13 attenuates ER stress-mediated neuronal apoptosis by activating
      Galphai/Galphaq-CK2 signaling in ischemic stroke.
AB  - Cerebral ischemia/reperfusion (I/R) injury-induced neuronal apoptosis contributes
      to the death and disability in patients with ischemic stroke. However, underlying
      mechanisms remain elusive and it lacks effective treatment. Here we reported that
      the expression of casein kinase 2 (CK2) was significantly reduced in brains of
      middle cerebral artery occlusion/reperfusion (MACO/R) model rats and oxygen
      glucose deprivation/reperfusion (OGD/R) model neurons, which was associated with
      the activation of eIF2-ATF4-CHOP signaling pathway, leading to neuronal
      apoptosis. Moreover, we found that apelin-13 significantly upregulated CK2
      expression and inhibited eIF2-ATF4-CHOP activation, attenuating cerebral I/R
      injury-induced infarct and neuronal apoptosis in MACO/R model rats and OGD/R
      model neurons. Furthermore, we demonstrated that the rescue effect of apelin-13
      on I/R injury-induced neuronal apoptosis was mediated by Galphai/Galphaq-CK2
      dependent inhibition of eIF2-ATF4-CHOP activation. These data indicated cerebral
      I/R injury reduced CK2 expression and activated eIF2-ATF4-CHOP signaling
      contributing to neuronal apoptosis, and apelin-13 can activate Galphai/Galphaq
      CK2 signaling attenuating eIF2-ATF4-CHOP-mediated neuronal apoptosis. It provides
      a novel insight that not only apelin-13 but also CK2 agonists may have
      therapeutic potential for protecting neurons from I/R injury-induced apoptosis,
      facilitating post-stroke recovery.

PMID- 29337147
TI  - Neuronal PTEN deletion in adult cortical neurons triggers progressive growth of
      cell bodies, dendrites, and axons.
AB  - Deletion of the phosphatase and tensin (PTEN) gene in neonatal mice leads to
      enlargement of the cell bodies of cortical motoneurons (CMNs) in adulthood
      (Gutilla et al., 2016). Here, we assessed whether PTEN deletion in adult mice
      would trigger growth of mature neurons. PTEN was deleted by injecting AAV-Cre
      into the sensorimotor cortex of adult transgenic mice with a lox-P flanked exon 5
      of the PTEN gene and Cre-dependent reporter gene tdTomato. PTEN-deleted CMN's
      identified by tdT expression and retrograde labeling with fluorogold (FG) were
      significantly enlarged four months following PTEN deletion, and continued to
      increase in size through the latest time intervals examined (12-15 months post
      deletion). Sholl analyses of tdT-positive pyramidal neurons revealed increases in
      dendritic branches at 6 months following adult PTEN deletion, and greater
      increases at 12 months. 12 months after adult PTEN deletion, axons in the
      medullary pyramids were significantly larger and G-ratios were higher. Mice with
      PTEN deletion exhibited no overt neurological symptoms and no seizures.
      Assessment of motor function on the rotarod and cylinder test revealed slight
      impairment of coordination with unilateral deletion; however, mice with bilateral
      PTEN deletion in the motor cortex performed better than controls on the rotarod
      at 8 and 10 months post-deletion. Our findings demonstrate that robust neuronal
      growth can be induced in fully mature cortical neurons long after the
      developmental period has ended and that this continuous growth occurs without
      obvious functional impairments.

PMID- 29337148
TI  - And Now, Death by Proton Pump Inhibitor?

PMID- 29337149
TI  - Just the FRAX: Management of Glucocorticoid-Induced Osteoporosis.

PMID- 29337150
TI  - Heptose 1,7-Bisphosphate Directed TIFA Oligomerization: A Novel PAMP-Recognizing
      Signaling Platform in the Control of Bacterial Infections.

PMID- 29337151
TI  - Development of the Enteric Nervous System: A Genetic Guide to the Perplexed.

PMID- 29337152
TI  - How to Obtain Training in Nutrition During the Gastroenterology Fellowship.

PMID- 29337153
TI  - Pancreatitis: A Tale of Two Proteases.

PMID- 29337154
TI  - Intraductal Papillary Mucinous Neoplasm as the Focus for Early Detection of
      Pancreatic Cancer.

PMID- 29337155
TI  - NVR 3-778 Plus Pegylated Interferon-alpha Treatment for Chronic Hepatitis B Viral
      Infections: Could 1 + 1 = 3?

PMID- 29337156
TI  - Nonceliac Gluten Sensitivity: What Is the Culprit?

PMID- 29337157
TI  - Update on the Use of Vonoprazan: A Competitive Acid Blocker.

PMID- 29337159
TI  - Colonoscopy Risks: What Is Known and What Are the Next Steps?

PMID- 29337160
TI  - Response to "XPA is primarily cytoplasmic but is transported into the nucleus
      upon UV damage".

PMID- 29337161
TI  - Cellular redox, cancer and human papillomavirus.
AB  - High-risk Human Papillomavirus (HR-HPV) is the causative agent of different human
      cancers. A persistent HR-HPV infection alters several cellular processes involved
      in cell proliferation, apoptosis, immune evasion, genomic instability and
      transformation. Cumulative evidence from past studies indicates that HR-HPV
      proteins are associated with oxidative stress (OS) and has been proposed as a
      risk factor for cancer development. Reactive oxygen and nitrogen species (RONS)
      regulate a plethora of processes inducing cellular proliferation, differentiation
      and death. Oxidative stress (OS) is generated when an imbalance in the redox
      state occurs due to deregulation of the oxidant and antioxidant systems, which,
      in turn, promotes the damage of DNA, proteins and lipids, allowing the
      accumulation of mutations and genome instability. OS has been associated with the
      establishment and development of different cancers, and it has recently been
      proposed as a co-factor in cervical cancer development. This review is focused on
      evidence regarding the association of OS with HR-HPV proteins, and the interplay
      of the viral proteins with different elements of the antioxidant and DNA damage
      response (DDR) systems, emphasizing the processes that might be required for the
      viral life cycle and viral DNA integration into the host genome, which is a key
      element in the carcinogenic process induced by HR-HPV.

PMID- 29337162
TI  - Antiviral activity of K22 against members of the order Nidovirales.
AB  - Recently, a novel antiviral compound (K22) that inhibits replication of a broad
      range of animal and human coronaviruses was reported to interfere with viral RNA
      synthesis by impairing double-membrane vesicle (DMV) formation (Lundin et al.,
      2014). Here we assessed potential antiviral activities of K22 against a range of
      viruses representing two (sub)families of the order Nidovirales, the
      Arteriviridae (porcine reproductive and respiratory syndrome virus [PRRSV],
      equine arteritis virus [EAV] and simian hemorrhagic fever virus [SHFV]), and the
      Torovirinae (equine torovirus [EToV] and White Bream virus [WBV]). Possible
      effects of K22 on nidovirus replication were studied in suitable cell lines. K22
      concentrations significantly decreasing infectious titres of the viruses included
      in this study ranged from 25 to 50 MUM. Reduction of double-stranded RNA
      intermediates of viral replication in nidovirus-infected cells treated with K22
      confirmed the anti-viral potential of K22. Collectively, the data show that K22
      has antiviral activity against diverse lineages of nidoviruses, suggesting that
      the inhibitor targets a critical and conserved step during nidovirus replication.

PMID- 29337163
TI  - Utility of ultra-deep sequencing for detection of varicella-zoster virus
      antiviral resistance mutations.
AB  - We report the first application of ultra-deep sequencing (UDS) to varicella
      zoster virus (VZV) genotypic antiviral testing in a case of acyclovir-resistant
      VZV infection initially detected by Sanger sequencing within a deeply
      immunocompromised heart transplant recipient. As added-value compared to Sanger
      analysis, UDS revealed complex dynamics of viral population under antiviral
      pressure. Varicella-zoster virus (VZV) is a ubiquitous human herpesvirus
      affecting populations worldwide. VZV is commonly acquired in youth whose primary
      infection usually manifests as benign varicella (chickenpox). After the initial
      infection, the virus establishes lifelong latency in sensory ganglia leading to a
      risk of subsequent reactivation. Reactivation usually results in the development
      of localized herpes zoster (HZ) lesions, a painful skin rash commonly known as
      shingles (Cohen, 2013). The incidence and severity of HZ increase with impaired
      specific cell-mediated immunity mainly as a result of increasing age, malignancy,
      immunodeficiency, organ transplantation, or immunosuppressive drug therapy
      (Cohen, 2013; Koo et al., 2014; Pavlopoulou et al., 2015). In particular, HZ
      remains a significant cause of morbidity among solid organ transplant (SOT)
      recipients, especially in patients undergoing heart transplantation (HT) compared
      with liver, kidney, or lung transplant recipients (Carby et al., 2007; Koo et
      al., 2014; Pavlopoulou et al., 2015). These particular individuals are at
      increased risk of primary infection, reactivation followed by dissemination with
      visceral involvement and associated with bacterial superinfection, and chronic
      recurrences (Cohen, 2013). VZV infections may also engender debilitating
      neuralgia among highly immunocompromised patients (Sampathkumar et al., 2009). HT
      is also associated with the risk of reactivation of other latent viruses
      belonging to the Herpesviridae family as herpes simplex virus (HSV). Currently
      licensed drugs to prevent or to cure HSV- or VZV-associated diseases target the
      viral DNA polymerase (Pol). Acyclovir (ACV) and its prodrug valacyclovir (VACV)
      are considered as the first-line therapy, whereas foscarnet (FOS) or cidofovir
      (CDV) constitute alternative options. After primophosphorylation by the viral
      thymidine kinase (TK), ACV targets the viral DNA polymerase and inhibits the
      viral genome replication by a chain termination mechanism. According to this
      mechanism of action, viral mutations conferring resistance to ACV have been
      mapped both in TK and Pol encoding genes. Viral mutations conferring resistance
      to FOS and CDV are only detected in Pol gene. VZV ACV-resistance is mostly
      mediated by TK alterations, consisting in either translational frameshifts,
      sometimes associated with premature stop codon, or amino acid substitutions. In
      the remaining cases, amino acid substitutions are detected within Pol (De et al.,
      2015; Piret and Boivin, 2014). Classically, Sanger sequencing has been recognized
      as the gold standard for the detection of drug resistance mutations (DRMs) within
      VZV TK and Pol genes (Perrier et al., 2016; Piret and Boivin, 2014). However,
      this approach cannot detect minor variants present at a frequency below 20%.
      Ultra-deep sequencing (UDS) has an enhanced sensitivity compared to Sanger method
      and allows quantitative evaluation of the viral mutants (Chin et al., 2013). We
      report here a case of VZV resistant infection in an HT recipient. Our
      retrospective study aimed at showing the utility of UDS for DRM detection as a
      complement of Sanger method.

PMID- 29337164
TI  - Identification of novel antivirals inhibiting recognition of Venezuelan equine
      encephalitis virus capsid protein by the Importin alpha/beta1 heterodimer through
      high-throughput screening.
AB  - Although the alphavirus Venezuelan equine encephalitis virus (VEEV) has been the
      cause of multiple outbreaks resulting in extensive human and equine mortality and
      morbidity, there are currently no anti-VEEV therapeutics available. VEEV
      pathogenicity is largely dependent on targeting of the viral capsid protein (CP)
      to the host cell nucleus through the nuclear transporting importin (Imp)
      alpha/beta1 heterodimer. Here we perform a high-throughput screen, combined with
      nested counterscreens to identify small molecules able to inhibit the
      Impalpha/beta1:CP interaction for the first time. Several compounds were able to
      significantly reduce viral replication in infected cells. Compound G281-1564 in
      particular could inhibit VEEV replication at low MUM concentration, while showing
      minimal toxicity, with steady state and dynamic quantitative microscopic
      measurements confirming its ability to inhibit CP nuclear import. This study
      establishes the principle that inhibitors of CP nucleocytoplasmic trafficking can
      have potent antiviral activity against VEEV, and represents a platform for future
      development of safe anti-VEEV compounds with high efficacy and specificity.

PMID- 29337165
TI  - Establishment of intracellular tenofovir-diphosphate as the key determinant for
      in vitro-in vivo translation of antiviral efficacy.
AB  - In vitro evaluation of tenofovir disproxil fumarate (TDF) and tenofovir
      alafenamide (TAF) revealed comparable antiviral effects with respect to the
      tenofovir-diphosphate (TFV-DP) level in human peripheral blood mononuclear cells
      (PBMCs), despite the EC50 values determined based on prodrug concentrations were
      nearly two orders of magnitude apart. In vivo EC50 obtained from meta-analyses
      were in good agreement with the in vitro results, indicating intracellular TFV-DP
      can be employed for in vitro-in vivo translation of viral inhibition for
      tenofovir prodrugs. Current analysis indicated that the intracellular
      concentrations of TFV-DP achieving maximal antiviral effect in vitro can be
      directly translatable in the clinic to accomplish maximal viral load suppression
      attainable by tenofovir-prodrugs.

PMID- 29337166
TI  - CD163 knockout pigs are fully resistant to highly pathogenic porcine reproductive
      and respiratory syndrome virus.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) causes severe
      economic losses to current swine production worldwide. Highly pathogenic PRRSV
      (HP-PRRSV), originated from a genotype 2 PRRSV, is more virulent than classical
      PRRSV and further exacerbates the economic impact. HP-PRRSV has become the
      predominant circulating field strain in China since 2006. CD163 is a cellular
      receptor for PRRSV. The depletion of CD163 whole protein or SRCR5 region
      (interaction site for the virus) confers resistance to infection of several PRRSV
      isolates in pigs or cultured host cells. In this study, we described the
      generation of a CD163 knockout (KO) pig in which the CD163 protein was ablated by
      using CRISPR/Cas9 gene targeting and somatic cell nuclear transfer (SCNT)
      technologies. Challenge with HP-PRRSV TP strain showed that CD163 KO pigs are
      completely resistant to viral infection manifested by the absence of viremia,
      antibody response, high fever or any other PRRS-associated clinical signs. By
      comparison, wild-type (WT) controls displayed typical signs of PRRSV infection
      and died within 2 weeks after infection. Deletion of CD163 showed no adverse
      effects to the macrophages on immunophenotyping and biological activity as
      hemoglobin-haptoglobin scavenger. The results demonstrated that CD163 knockout
      confers full resistance to HP-PRRSV infection to pigs without impairing the
      biological function associated with the gene.

PMID- 29337167
TI  - Prognostic Factors for Survival Outcome of High-Grade Multicentric Glioma.
AB  - OBJECTIVE: The purpose of this study was to perform a survival analysis of
      patients with high-grade multicentric gliomas and to assess the influence of
      various prognostic factors on overall survival (OS). METHODS: A literature search
      on PubMed and Web of Science was performed for literature in English published
      from 1880 to October 2017. Detailed information including demographics, clinical
      characteristics, treatments, critical events, and time to events for survival
      analysis were extracted from the included articles. RESULTS: A total of 73 cases
      from 25 published articles were selected for analysis. Univariate analysis showed
      the surgery (SB/SR), age (<54/>=54 years), radiotherapy (Y/N), and
      suprainfratentorial gliomas (Y/N) had significant correlations with OS.
      Multivariate analysis showed that age, surgery, and radiotherapy were independent
      prognostic factors. Univariate and multivariate analysis revealed radiotherapy
      and radiotherapy combined with chemotherapy were independent prognostic factors
      for surgical patients' OS. CONCLUSIONS: This comprehensive analysis of
      multicentric glioma patients revealed that age younger than 54 years, surgical
      resection, and radiotherapy were significantly associated with improved survival
      and were independent prognostic factors for OS. Radiotherapy and radiotherapy
      combined with chemotherapy were independent prognostic factors for surgical
      patients' OS as well.

PMID- 29337168
TI  - Aggressive Resection of Congenital Lumbosacral Lipomas in Adults: Indications,
      Techniques, and Outcomes in 122 Patients.
AB  - OBJECTIVE: The authors reviewed the treatment of adult patients with congenital
      intraspinal lipomas with total/near-total resection and discussed their
      preoperative characteristics, prognostic factors, and surgical outcomes. METHODS:
      Medical records of 122 adult patients with congenital lumbosacral lipomas
      undergoing total/near-total resection were systematically analyzed. The cohort
      was subdivided into 3 groups depending on symptom onset age: group 1 (<=5 years,
      n = 40), group 2 (>5 years but <18 years, n = 33), and group 3 (>18 years, n =
      49). Preoperative and postoperative neurologic status were compared between
      groups and analyzed as a whole. RESULTS: The most common symptom was bladder
      dysfunction (82.0%), followed by constipation (76.2%). At the 3-month follow-up,
      improvement was noted in most patients presenting with pain (87.2%) and
      neuropathic ulcers (70.0%). Overall, neurologic status was improved in 73.0% of
      patients and stabilized in 19.7% of patients. A binary logistic regression model
      identified shorter preoperative duration (P = 0.013) and preoperative pain (P =
      0.005) as independent predictors of postoperative improvement. Neurosurgical
      complications developed in 16 patients, and wound complications occurred in 2
      patients. Two of 3 patients who had recurred symptoms underwent repeated
      detethering surgery during long-term follow-up. CONCLUSIONS: Despite longer
      preoperative duration than the pediatric population, adult patients with
      lumbosacral lipomas can still benefit from total/near-total resection especially
      regarding pain and foot ulcers, with low surgery-related morbidity. The long-term
      advantage of resecting additional lipoma in adults remains a point of discussion.

PMID- 29337170
TI  - Virtual Cerebral Aneurysm Clipping with Real-Time Haptic Force Feedback in
      Neurosurgical Education.
AB  - OBJECTIVE: Realistic, safe, and efficient modalities for simulation-based
      training are highly warranted to enhance the quality of surgical education, and
      they should be incorporated in resident training. The aim of this study was to
      develop a patient-specific virtual cerebral aneurysm-clipping simulator with
      haptic force feedback and real-time deformation of the aneurysm and vessels.
      METHODS: A prototype simulator was developed from 2012 to 2016. Evaluation of
      virtual clipping by blood flow simulation was integrated in this software, and
      the prototype was evaluated by 18 neurosurgeons. In 4 patients with different
      medial cerebral artery aneurysms, virtual clipping was performed after real-life
      surgery, and surgical results were compared regarding clip application, surgical
      trajectory, and blood flow. RESULTS: After head positioning and craniotomy,
      bimanual virtual aneurysm clipping with an original forceps was performed. Blood
      flow simulation demonstrated residual aneurysm filling or branch stenosis. The
      simulator improved anatomic understanding for 89% of neurosurgeons. Simulation of
      head positioning and craniotomy was considered realistic by 89% and 94% of users,
      respectively. Most participants agreed that this simulator should be integrated
      into neurosurgical education (94%). Our illustrative cases demonstrated that
      virtual aneurysm surgery was possible using the same trajectory as in real-life
      cases. Both virtual clipping and blood flow simulation were realistic in broad
      based but not calcified aneurysms. Virtual clipping of a calcified aneurysm could
      be performed using the same surgical trajectory, but not the same clip type.
      CONCLUSIONS: We have successfully developed a virtual aneurysm-clipping
      simulator. Next, we will prospectively evaluate this device for surgical
      procedure planning and education.

PMID- 29337171
TI  - Is Early Tracheostomy Better for Severe Traumatic Brain Injury? A Meta-Analysis.
AB  - BACKGROUND: Tracheostomy has proven benefits for patients requiring prolonged
      mechanical ventilation. However, whether early tracheostomy (ET; <10 days after
      injury) can also improve outcomes in patients with severe traumatic brain injury
      (TBI) (Glasgow Coma Scale score <=8) remains controversial. The aim of this study
      was to clarify this question. METHODS: We searched 4 databases (PubMed, Web of
      Science, Elsevier ScienceDirect, and Cochrane Library) for articles comparing the
      outcomes of ET with late tracheotomy or prolonged intubation in patients with
      severe TBI. Two reviewers were asked to record the major outcome data as follows:
      length of intensive care unit (ICU) stay, duration of mechanical ventilation,
      mortality, and incidence of pneumonia. Both random-effects and fixed-effects
      models were used. RESULTS: Eight studies met our inclusion criteria, with a total
      of 797 patients in the ET group and 871 patients in the late tracheostomy or
      prolonged intubation (not-ET) group. A meta-analysis of these 8 studies suggested
      that ET could reduce the length of ICU stay (mean difference [MD], -3.08; 95%
      confidence interval [CI], -3.75 to -2.41), duration of mechanical ventilation
      (MD, -4.92; 95% CI, -6.82 to -3.02), length of hospital stay (MD, -4.79; 95% CI, 
      8.63 to -0.94), and incidence of pneumonia (odds ratio [OR], 0.64; 95% CI, 0.53
      0.78), but seemed to be independent of mortality (OR, 1.25; 95% CI, 0.90-1.75).
      CONCLUSIONS: The available evidence suggests that ET may reduce the length of ICU
      and hospital stays, duration of mechanical ventilation, and incidence of
      pneumonia in patients with severe TBI. Well-designed randomized controlled trials
      are needed to confirm these findings.

PMID- 29337169
TI  - The Prognostic Roles of Gender and O6-Methylguanine-DNA Methyltransferase
      Methylation Status in Glioblastoma Patients: The Female Power.
AB  - BACKGROUND: Clinical and molecular factors are essential to define the prognosis
      in patients with glioblastoma (GBM). O6-methylguanine-DNA methyltransferase
      (MGMT) methylation status, age, Karnofsky Performance Status (KPS), and extent of
      surgical resection are the most relevant prognostic factors. Our investigation of
      the role of gender in predicting prognosis shows a slight survival advantage for
      female patients. METHODS: We performed a prospective evaluation of the Project of
      Emilia Romagna on Neuro-Oncology (PERNO) registry to identify prognostic factors
      in patients with GBM who received standard treatment. RESULTS: A total of 169
      patients (99 males [58.6%] and 70 females [41.4%]) were evaluated prospectively.
      MGMT methylation was evaluable in 140 patients. Among the male patients, 36 were
      MGMT methylated (25.7%) and 47 were unmethylated (33.6%); among the female
      patients, 32 were methylated (22.9%) and 25 were unmethylated (17.9%). Survival
      was longer in the methylated females compared with the methylated males (P =
      0.028) but was not significantly different between the unmethylated females and
      the unmethylated males (P = 0.395). In multivariate analysis, gender and MGMT
      methylation status considered together (methylated females vs. methylated males;
      hazard ratio [HR], 0.459; 95% confidence interval [CI], 0.242-0.827; P = 0.017),
      age (HR, 1.025; 95% CI, 1.002-1.049; P = 0.032), and KPS (HR, 0.965; 95% CI,
      0.948-0.982; P < 0.001) were significantly correlated with survival. CONCLUSIONS:
      Survival was consistently longer among MGMT methylated females compared with
      males. Gender can be considered as a further prognostic factor.

PMID- 29337173
TI  - Improving bystander defibrillation for out-of-hospital cardiac arrest:
      Capability, opportunity and motivation.

PMID- 29337172
TI  - Organ support therapy in the intensive care unit and return to work in out-of
      hospital cardiac arrest survivors-A nationwide cohort study.
AB  - AIM: With increased survival after out-of-hospital cardiac arrest (OHCA), impact
      of the post-resuscitation course has become important. Among 30-day OHCA
      survivors, we investigated associations between organ support therapy in the
      Intensive Care Unit (ICU) and return to work. METHODS: This Danish nationwide
      cohort-study included 30-day-OHCA-survivors who were employed prior to arrest. We
      linked OHCA data to information on in-hospital care and return to work. For
      patients admitted to an ICU and based on renal replacement therapy (RRT),
      cardiovascular support and mechanical ventilation, we assessed the prognostic
      value of organ support therapies in multivariable Cox regression models. RESULTS:
      Of 1087 30-day survivors, 212 (19.5%) were treated in an ICU with 0-1 types of
      organ support, 494 (45.4%) with support of two organs, 26 (2.4%) with support of
      three organs and 355 (32.7%) were not admitted to an ICU. Return to work
      increased with decreasing number of organs supported, from 53.8% (95% CI: 49.5
      70.1%) in patients treated with both RRT, cardiovascular support and mechanical
      ventilation to 88.5% (95% CI: 85.1-91.8%) in non-ICU-patients. In 732 ICU
      patients, ICU-patients with support of 3 organs had significantly lower adjusted
      hazard ratios (HR) of returning to work (0.50 [95% CI: 0.30-0.85] compared to ICU
      patients with support of 0-1 organ. The corresponding HR was 0.48 [95% CI: 0.30
      0.78] for RRT alone. CONCLUSIONS: In 30-day survivors of OHCA, number of organ
      support therapies and in particular need of RRT were associated with reduced rate
      of return to work, although more than half of these latter patients still
      returned to work.

PMID- 29337174
TI  - Palliative care utilization following out-of-hospital cardiac arrest in the
      United States.
AB  - AIMS: Palliative care (PC) has become an integral component of comprehensive care
      provided to critically ill patients. Little is known about the utilization of
      palliative care following Out-of-Hospital Cardiac Arrest (OHCA) in the United
      States. METHODS: We used the 2002-2013 National Inpatient Sample database to
      identify adults >=18 years old with an ICD-9-CM principal diagnosis code of
      cardio-respiratory arrest or ventricular fibrillation (VF). Patients were
      categorized into two groups based on the presence of PC, then compared using
      Pearson chi2 test for categorical variables and linear regression for continuous
      variables. Multiple linear and logistic regression models were conducted to
      identify factors associated with PC, and temporal trends in PC utilization.
      RESULTS: Of the 154,177 patients hospitalized with OHCA in the U.S, 11,260 (7.3%)
      had PC consultations during hospitalization. PC Utilization increased from 1.5%
      in 2002 to 16.7% in 2013 (P-trend < 0.001). Patients who received Palliative care
      were older (mean age 70.7 +/- 0.3 vs 65.9 +/- 0.1), more likely to be female
      (45.8% vs 40.5%), and had higher Charlson comorbidity index >=2 (55.8% vs 46.8%).
      In adjusted analyses, older age, female gender, Caucasian race, higher Charlson
      comorbidity index, multiorgan failure, metastatic cancer, non-shockable rhythm,
      admission to larger, urban and teaching hospitals were all associated with higher
      PC utilization. CONCLUSION: We observed significant increase in the utilization
      of palliative care consultations following OHCA over the study period. This was
      influenced by multiple patient and hospital factors. Further investigations are
      needed to identify the appropriate cost-effective use of palliative care
      following cardiac arrest.

PMID- 29337175
TI  - Minimally invasive versus extensile lateral approach for sanders type II and III
      calcaneal fractures: A meta-analysis of randomized controlled trials.
AB  - BACKGROUND: The use of less-invasive techniques in the treatment of displaced
      intra-articular calcaneal fractures (DIACFs) remains controversial. No prior meta
      analysis has considered the influence of differences in the fracture type. Thus,
      our meta-analysis aimed to investigate the efficacy and safety of minimally
      invasive (MI) in Sanders type II and III fractures. MATERIALS AND METHODS: A
      comprehensive search was performed to identify RCTs comparing MI using sinus
      tarsi approach (STA) or percutaneous reduction (PR) to open reduction (OR) via
      extensile lateral approach (ELA) from the Cochrane Library, PubMed, Embase and
      CNKI. Dichotomous and continuous data were pooled using risk ratio (RR) and mean
      difference (MD), respectively, with 95% confidence intervals (CIs). The data were
      analysed using Review Manager 5.3. RESULTS: Eight RCTs (495 participants) were
      selected in our meta-analysis. Based on the American Orthopaedic Foot and Ankle
      Society score (AOFAS), both general pooled data and subgroup analysis of Sanders
      type II fractures indicated that MI improves functional outcomes, while in the
      Sanders type III subgroup, the advantage disappeared. Additionally, the pooled
      results showed that MI reduces the rate of wound complications; lowers the VAS
      score; and shortens the time to surgery, duration of surgery and length of
      hospital stay. There was no statistical significance with respect to recovery of
      calcaneus length and width or improvement of Gissane's angle and Bohler's angle.
      CONCLUSION: Our meta-analysis suggests that MI and ELA are equally effective
      treating Sanders type II and III fractures. However, MI is effective in improving
      the AOFAS score (Sanders type II); reducing the rate of wound complications; and
      shortening the time to surgery, duration of surgery and length of hospital stay.

PMID- 29337176
TI  - Comparison of the diagnostic performances of ultrasonography, CT and fine needle
      aspiration cytology for the prediction of lymph node metastasis in patients with
      lymph node dissection of papillary thyroid carcinoma: A retrospective cohort
      study.
AB  - PURPOSE: To evaluate the diagnostic performances of ultrasonographic (US)
      findings, computed tomography (CT) findings and fine needle aspiration cytology
      (FNAC) for the prediction of cervical lymph node (LN) metastases of papillary
      thyroid carcinoma (PTC) to determine which LN should be dissected. METHODS: 376
      LNs in 302 patients who underwent both US-guided skin surface LN markings and CT
      before LN dissection were analyzed retrospectively. Indications for LN dissection
      were suspicious US findings of LN metastases (n = 300), suspicious CT findings (n
      = 67) or surgeon's request (n = 9). Diagnostic performances of US, CT and FNAC
      (including thyroglobulin (Tg)) were evaluated. The correlations of suspicious US,
      CT finding or malignant FNAC with the size, number and the presence of extranodal
      extension of metastatic LNs were analyzed. RESULTS: US indication of LN
      dissection was significantly correlated with malignancy (p < .0001). Values of
      area under the curve of highly suspicious US findings and FNAC+Tg were
      significantly higher than that of CT (0.786, 0.878, 0.585, p < .0001,
      respectively). Suspicious US, CT findings and malignant FNAC+Tg were
      significantly associated with the largest size of metastatic LNs (p = .003, p =
      .0003, and p = .0006, respectively) and total number of metastatic LNs (p = .007,
      p = .038, and p = .005, respectively). CONCLUSION: The diagnostic performance of
      US or FNAC was superior to CT and highly suspicious US findings could be
      complimentary to FNAC results in predicting LN metastases of PTC. LN dissection
      should be performed for the LNs with any suspicious US findings or malignant FNAC
      results rather than LNs with only suspicious CT findings.

PMID- 29337177
TI  - Laparoscopic versus open pancreatectomy for pancreatic ductal adenocarcinoma: A
      systematic review and meta-analysis.
AB  - BACKGROUND: Laparoscopic pancreatic surgery (LPS) has been widely used in the
      treatment of benign and low-grade pancreatic diseases. It is necessary to expand
      the current knowledge on the feasibility and safety of LPS for pancreatic ductal
      adenocarcinoma (PDAC) by systematic reviewing the published studies and analyzing
      them by meta-analysis. METHODS: Original articles compared LPS with open
      pancreatic surgery (OPS) for PDAC, published from January 1994 to August 2017
      were searched in medical databases. Postoperative pancreatic fistula (POPF),
      morbidity, mortality, operation time, blood loss, transfusion, hospital stay,
      retrieved lymph nodes (RLNs), and survival outcomes were compared. RESULTS:
      Fourteen studies with a total of 13174 patients (1705 in LPS and 11469 in OPS)
      were included for the meta-analysis. LPS showed less morbidity (RR = 0.78, 95%CI:
      0.66-0.92, P < .01), blood loss (WMD = -298.05 ml, 95% CI, -482.98~-113.12 ml; P
      < .01), shorter hospital stay (WMD = -2.86, 95%CI, -3.85~-1.87; P < .01), more
      RLNs (WMD = 1.47, 95%CI: 0.15-2.78; P = .03) and comparable POPF (RR = 1.12,
      95%CI: 0.82-1.53, P = .50), operation time (WMD = 22.23 min; 95%CI: -19.56-64.01,
      P = .30), and 5-year overall survival (HR = 0.92, 95%CI: 0.80-1.06; P = .23)
      compared to OPS. CONCLUSION: LPS can be performed safely in carefully selected
      patients with PADC and would improve the surgical outcomes. Considering the
      limitation of study design, the conclusions should be interpret cautiously and
      warrant to be confirmed by randomized controlled studies.

PMID- 29337178
TI  - Multifocality as a prognostic factor in thyroid cancer: A meta-analysis.
AB  - BACKGROUND: Thyroid cancer is one of the most common endocrine cancers whose
      incidence has been steadily increasing. Previous studies have suggested that
      multifocality in thyroid cancer is associated with poor prognosis. The present
      study aims to quantify the data on multifocality as a factor indicating poor
      prognosis by meta-analysis. METHODS: A systematic search was carried out using
      the electronic databases PubMed and Medline. We searched for articles containing
      keywords of multifocality and thyroid cancer, as well as risk factors and
      prognostic factors for thyroid cancer (Lymph node metastases, extrathyroidal
      extension, distant metastases, disease recurrence, Age, tumour size. and gender).
      Data sets containing hazard ratios and odds ratios were then compared. RESULTS:
      The meta-analysis was performed using a total of 21 articles, showed that
      multifocality is associated with an increased risk of development of LNM (12
      Studies: OR = 1.87; 95% CI = 1.51-2.32; I2 = 49.11; p-value = .03),
      Extrathyroidal extension (15 Studies: OR = 3.18; 95% CI = 0.69-14.71; I2 = 95.62;
      p-value <.001), Tumour Size > 1 cm (3 Studies: OR = 2.75; 95% CI = 1.95-3.89; I2
      = 0.00 and p-value = .88) and disease recurrence (5 Studies: HR = 2.81; 95% CI =
      1.07-7.36; I2 = 95.85; p-value < .001). Risk factors that did not significantly
      contribute to a higher incidence of multifocality include Age >45, Male Gender.
      CONCLUSIONS: Multifocality in thyroid cancer is a significant risk factor for
      disease progression and increases the risk of disease recurrence. The present
      study suggests that patients who have multifocal disease should therefore be
      managed more aggressively from an operative and post-operative perspective.

PMID- 29337179
TI  - Surgical treatment of recurrent varicose veins in the lower limbs associated with
      endovascular treatment of iliac vein stenosis.
AB  - OBJECTIVE: We present our experience with endovascular surgery for recurrent
      varicose veins (RVV) of the lower limbs combined with the iliac vein compression
      syndrome (IVCS). MATERIALS AND METHODS: This study was a retrospective analysis
      of 6 patients with RVVs combined with IVCS who were admitted to our hospital
      between January 2007 and December 2014. Transfemoral venography was performed to
      confirm IVCS. Balloon dilation and stent placement were successful in all 6
      patients. The varicose veins were treated by traditional surgery after the
      endovascular therapy. The visual analog pain scale (VAS) score and venous
      clinical severity score (VCSS) were collected before surgery and at 6-months
      follow-up, and were analyzed using the paired student t-test. Patency of the
      iliac vein was assessed via duplex Doppler ultrasound. RESULTS: The rate of
      technical success was 100%. There was a significant (p < .001) improvement in
      VCSS postoperatively. During the 6-month follow-up period, no RVVs were observed
      and the rate of iliac vein patency was 100%. Importantly, VAS ratings also
      decreased significantly (p < .001) during the follow-up. CONCLUSION: Endovascular
      surgery for IVCS combined with traditional surgery focused on varicose veins is
      an effective procedure for treating RVVs of the lower limbs associated with IVCS
      within 6 months.

PMID- 29337180
TI  - Impact of an acute surgical unit in appendicectomy outcomes: A systematic review
      and meta-analysis.
AB  - BACKGROUND: The provision of emergency general surgical services is undergoing a
      paradigm shift towards a consultant led, patient centered model in order to
      improve patient outcomes. The aim of this current study is to use meta-analytical
      techniques to assess the efficacy of acute surgical unit (ASU) in appendectomy.
      METHODS: A meta-analysis was conducted according to the PRISMA guidelines. A
      comprehensive literature search of PubMed, Embase and Scopus for published
      studies comparing ASU and traditional (TRAD) model on appendectomy outcomes was
      performed. Random-effects methods were used to analyze key outcomes with data
      presented as odds ratio (OR) with 95% confidence interval (CI). RESULTS: Fourteen
      comparative studies describing outcomes in 7980 patients were identified, 4258
      patients were included in the ASU model (53.4%). ASU model had a shorter time to
      theatre (WMD: -0.40, 95% CI: -0.65 to 0.15, p: 0.002), length of hospital stay
      (WMD: -0.25, 95% CI: -0.46 to -0.05, p: 0.02) and complication rate (OR: 0.76,
      95% CI: 0.59 to 0.99, p: 0.04) for appendectomy patients. ASU model did not
      significantly affect night time operating (OR: 1.04, 95% CI: 0.66 to 1.65, p:
      0.86) negative appendectomy rates (OR: 0.98, 95% CI: 0.77-1.27, p: 0.91) or
      conversion rate (OR: 1.45, 95% CI: 0.70 to 2.98, p: 0.32). CONCLUSION: ASU model
      improves outcomes and quality of care in patients undergoing emergency
      appendectomy without any adverse implications.

PMID- 29337182
TI  - Human Pancreatic Tumor Organoids Reveal Loss of Stem Cell Niche Factor Dependence
      during Disease Progression.
AB  - Despite recent efforts to dissect the inter-tumor heterogeneity of pancreatic
      ductal adenocarcinoma (PDAC) by determining prognosis-predictive gene expression
      signatures for specific subtypes, their functional differences remain elusive.
      Here, we established a pancreatic tumor organoid library encompassing 39 patient
      derived PDACs and identified 3 functional subtypes based on their stem cell niche
      factor dependencies on Wnt and R-spondin. A Wnt-non-producing subtype required
      Wnt from cancer-associated fibroblasts, whereas a Wnt-producing subtype
      autonomously secreted Wnt ligands and an R-spondin-independent subtype grew in
      the absence of Wnt and R-spondin. Transcriptome analysis of PDAC organoids
      revealed gene-expression signatures that associated Wnt niche subtypes with GATA6
      dependent gene expression subtypes, which were functionally supported by genetic
      perturbation of GATA6. Furthermore, CRISPR-Cas9-based genome editing of PDAC
      driver genes (KRAS, CDKN2A, SMAD4, and TP53) demonstrated non-genetic acquisition
      of Wnt niche independence during pancreas tumorigenesis. Collectively, our
      results reveal functional heterogeneity of Wnt niche independency in PDAC that is
      non-genetically formed through tumor progression.

PMID- 29337181
TI  - A Non-canonical BCOR-PRC1.1 Complex Represses Differentiation Programs in Human
      ESCs.
AB  - Polycomb group proteins regulate self-renewal and differentiation in many stem
      cell systems. When assembled into two canonical complexes, PRC1 and PRC2, they
      sequentially deposit H3K27me3 and H2AK119ub histone marks and establish
      repressive chromatin, referred to as Polycomb domains. Non-canonical PRC1
      complexes retain RING1/RNF2 E3-ubiquitin ligases but have unique sets of
      accessory subunits. How these non-canonical complexes recognize and regulate
      their gene targets remains poorly understood. Here, we show that the BCL6 co
      repressor (BCOR), a member of the PRC1.1 complex, is critical for maintaining
      primed pluripotency in human embryonic stem cells (ESCs). BCOR depletion leads to
      the erosion of Polycomb domains at key developmental loci and the initiation of
      differentiation along endoderm and mesoderm lineages. The C terminus of BCOR
      regulates the assembly and targeting of the PRC1.1 complex, while the N terminus
      contributes to BCOR-PRC1.1 repressor function. Our findings advance understanding
      of Polycomb targeting and repression in ESCs and could apply broadly across
      developmental systems.

PMID- 29337183
TI  - Temporal Layering of Signaling Effectors Drives Chromatin Remodeling during Hair
      Follicle Stem Cell Lineage Progression.
AB  - Tissue regeneration relies on resident stem cells (SCs), whose activity and
      lineage choices are influenced by the microenvironment. Exploiting the
      synchronized, cyclical bouts of tissue regeneration in hair follicles (HFs), we
      investigate how microenvironment dynamics shape the emergence of stem cell
      lineages. Employing epigenetic and ChIP-seq profiling, we uncover how signal
      dependent transcription factors couple spatiotemporal cues to chromatin dynamics,
      thereby choreographing stem cell lineages. Using enhancer-driven reporters,
      mutagenesis, and genetics, we show that simultaneous BMP-inhibitory and WNT
      signals set the stage for lineage choices by establishing chromatin platforms
      permissive for diversification. Mechanistically, when binding of BMP effector
      pSMAD1 is relieved, enhancers driving HF-stem cell master regulators are
      silenced. Concomitantly, multipotent, lineage-fated enhancers silent in HF-stem
      cells become activated by exchanging WNT effectors TCF3/4 for LEF1. Throughout
      regeneration, lineage enhancers continue reliance upon LEF1 but then achieve
      specificity by accommodating additional incoming signaling effectors. Barriers to
      progenitor plasticity increase when diverse, signal-sensitive transcription
      factors shape LEF1-regulated enhancer dynamics.

PMID- 29337184
TI  - When drugs plasticize film coatings: Unusual formulation effects observed with
      metoprolol and Eudragit RS.
AB  - Metoprolol tartrate and metoprolol free base loaded pellet starter cores were
      coated with Eudragit RS, plasticized with 25% triethyl citrate (TEC). The initial
      drug loading and coating level were varied from 10 to 40 and 0 to 20%,
      respectively. Drug release was measured in 0.1 N HCl and phosphate buffer pH 7.4.
      The water uptake and swelling kinetics, mechanical properties and TEC leaching
      of/from coated pellets and/or thin, free films of identical composition as the
      film coatings were monitored. The following unusual tendencies were observed: (i)
      the relative drug release rate from coated pellets increased with increasing
      initial drug content, and (ii) drug release from pellets was much faster for
      metoprolol free base compared to metoprolol tartrate, despite its much lower
      solubility (factor >70). These phenomena could be explained by plasticizing
      effects of the drug for the polymeric film coatings. In particular: 1) Metoprolol
      free base is a much more potent plasticizer for Eudragit RS than the tartrate,
      leading to higher film permeability and overcompensating the pronounced
      differences in drug solubility. Also, Raman imaging revealed that substantial
      amounts of the free base migrated into the film coatings, whereas this was not
      the case for the tartrate. 2) The plasticizing effects of the drug for the film
      coating overcompensated potential increasing limited solubility effects when
      increasing the initial drug loading from 10 to 40%. In summary, this study
      clearly demonstrates how important the plasticization of polymeric controlled
      release film coatings by drugs can be, leading to unexpected formulation effects.

PMID- 29337185
TI  - Proliposome tablets manufactured using a slurry-driven lipid-enriched powders:
      Development, characterization and stability evaluation.
AB  - Proliposome powders were prepared via a slurry method using sorbitol or D
      mannitol as carbohydrate carriers in 1:10 or 1:15 w/w lipid phase to carrier
      ratios. Soya phosphatidylcholine (SPC) and cholesterol were employed as a lipid
      phase and Beclometasone dipropionate (BDP) was incorporated as a model drug.
      Direct compaction using a Minipress was applied on the lipid-enriched powder in
      order to manufacture proliposome tablets. Sorbitol-based proliposome tablets in a
      1:15 w/w ratio were found to be the best formulation as it exhibited excellent
      powder flowability with an angle of repose of 25.62 +/- 1.08 degrees , and when
      compacted the resultant tablets had low friability (0.20 +/- 0.03%), appropriate
      hardness (crushing strength) (120.67 +/- 12.04 N), short disintegration time
      (5.85 +/- 0.66 min), and appropriate weight uniformity. Moreover, upon hydration
      into liposomes, the entrapment efficiency for sorbitol formulations in both 1:10
      and 1:15 lipid to carrier ratios were significantly higher (53.82 +/- 6.42% and
      57.43 +/- 9.12%) than D-mannitol formulations (39.90 +/- 4.30% and 35.22 +/-
      6.50%), respectively. Extended stability testing was conducted for 18 months, at
      three different temperature conditions (Fridge Temperature (FT; 6  degrees C),
      Room Temperature (RT; 22  degrees C) and High Temperature (HT; 40  degrees C))
      for sorbitol-based proliposome tablets (1:15 w/w ratio). Volume median diameter
      (VMD) and zeta potential significantly changed from 5.90 +/- 0.70 um to 14.79 +/-
      0.79 um and from -3.08 +/- 0.26 mV to -11.97 +/- 0.26 mV respectively at month
      18, when samples were stored under HT conditions. Moreover, the entrapment
      efficiency of BDP decreased from 57.43 +/- 9.12% to 17.93 +/- 5.37% following 18
      months storage under HT conditions. Overall, in this study for the first time,
      proliposome tablets were manufactured and thoroughly characterized, and sorbitol
      showed to be a promising carrier.

PMID- 29337186
TI  - Lipoprotein Signal Peptidase Inhibitors with Antibiotic Properties Identified
      through Design of a Robust In Vitro HT Platform.
AB  - As resistance to antibiotics increases, the exploration of new targets and
      strategies to combat pathogenic bacteria becomes more urgent. Ideal protein
      targets are required for viability across many species, are unique to prokaryotes
      to limit effects on the host, and have robust assays to quantitate activity and
      identify inhibitors. Lipoprotein signal peptidase (Lsp) is a transmembrane
      aspartyl protease required for lipoprotein maturation and comprehensively fits
      these criteria. Here, we have developed the first in vitro high-throughput assay
      to monitor proteolysis by Lsp. We employed our high-throughput screen assay
      against 646,275 compounds to discover inhibitors of Lsp and synthesized a range
      of analogs to generate molecules with nanomolar half maximal inhibitory
      concentration values. Importantly, our inhibitors are effective in preventing the
      growth of E. coli cultures in the presence of outer-membrane permeabilizer PMBN
      and should facilitate development of antibacterial agents with a novel mechanism
      of action to treat antibiotic-resistant bacteria.

PMID- 29337187
TI  - Metabolomics Reveals that Dietary Xenoestrogens Alter Cellular Metabolism Induced
      by Palbociclib/Letrozole Combination Cancer Therapy.
AB  - Recently, the palbociclib/letrozole combination therapy was granted accelerated
      US FDA approval for the treatment of estrogen receptor (ER)-positive breast
      cancer. Since the underlying metabolic effects of these drugs are yet unknown, we
      investigated their synergism at the metabolome level in MCF-7 cells. As
      xenoestrogens interact with the ER, we additionally aimed at deciphering the
      impact of the phytoestrogen genistein and the estrogenic mycotoxin zearalenone. A
      global metabolomics approach was applied to unravel metabolite and pathway
      modifications. The results clearly showed that the combined effects of
      palbociclib and letrozole on cellular metabolism were far more pronounced than
      that of each agent alone and potently influenced by xenoestrogens. This behavior
      was confirmed in proliferation experiments and functional assays. Specifically,
      amino acids and central carbon metabolites were attenuated, while higher
      abundances were observed for fatty acids and most nucleic acid-related
      metabolites. Interestingly, exposure to model xenoestrogens appeared to
      counteract these effects.

PMID- 29337189
TI  - A well-circumscribed lobulated tumor on the hard palatal mucosa in a child.

PMID- 29337188
TI  - Abrogation of Fam20c altered cell behaviors and BMP signaling of immortalized
      dental mesenchymal cells.
AB  - FAM20C mutations compromise the mineralization of skeleton and tooth in both
      human and mouse. Putatively, the mineralization disorder is attributed to the
      elevated fibroblast growth factor 23 (FGF23), which reduced the serum phosphorus
      by suppressing the reabsorption of phosphorus in kidney. Besides the regulation
      on systemic phosphorus homeostasis, FAM20C was also implicated to regulate cell
      behaviors and gene expression through a cell-autonomous manner. To identify the
      primary effects of Fam20c on dental mesenchymal cells, mouse Fam20c-deficient
      dental mesenchymal cells were generated by removing the floxed alleles from the
      immortalized mouse Fam20cf/f dental mesenchymal cells with Cre-expressing
      lentivirus. The removal of Fam20c exerted no impact on cell morphology, but
      suppressed the proliferation and mobility of the dental mesenchymal cells. Fam20c
      deficiency also significantly reduced the expression of Osterix, Runx2, type I
      Collagen a 1 (Col1a1), Alkaline phosphatase (Alpl) and the members of the small
      integrin-binding ligand, N-linked glycoprotein (SIBLING) family, but increased
      Fgf23 expression. Consistently, the in vitro mineralization of Fam20c-deficient
      dental mesenchymal cells was severely disabled. However, supplements of the non
      collagenous proteins from wild type rat dentin failed to rescue the compromised
      mineralization, suggesting that the roles of FAM20C in tooth mineralization are
      more than phosphorylating local matrices and regulating systemic phosphorus
      metabolism. Moreover, the down-regulated BMP signaling pathways in the Fam20c
      deficient dental mesenchymal cells revealed that the kinase activity of FAM20C
      might be required to maintain BMP signaling. In summary, our study discloses that
      Fam20c indeed regulates cell behaviors and cell signaling pathway in a cell
      autonomous manner.

PMID- 29337191
TI  - The classification of azodicarbonamide (ADCA) as a respiratory sensitiser; adding
      to the weight of evidence.

PMID- 29337190
TI  - Binding of ferredoxin to algal photosystem I involves a single binding site and
      is composed of two thermodynamically distinct events.
AB  - Despite the impressive progress made in recent years in understanding the early
      steps in charge separation within the photosynthetic reaction centers, our
      knowledge of how ferredoxin (Fd) interacts with the acceptor side of photosystem
      I (PSI) is not as well developed. Fd accepts electrons after transiently docking
      to a binding site on the acceptor side of PSI. However, the exact location, as
      well as the stoichiometry, of this binding have been a matter of debate for more
      than two decades. Here, using Isothermal Titration Calorimetry (ITC) and purified
      components from wild type and mutant strains of the green algae Chlamydomonas
      reinhardtii we show that PSI has a single binding site for Fd, and that the
      association consists of two distinct binding events, each with a specific
      association constant.

PMID- 29337192
TI  - Combining machine learning models of in vitro and in vivo bioassays improves rat
      carcinogenicity prediction.
AB  - In vitro genotoxicity bioassays are cost-efficient methods of assessing potential
      carcinogens. However, many genotoxicity bioassays are inappropriate for detecting
      chemicals eliciting non-genotoxic mechanisms, such as tumour promotion, this
      necessitates the use of in vivo rodent carcinogenicity (IVRC) assays. In silico
      IVRC modelling could potentially address the low throughput and high cost of this
      assay. We aimed to develop and combine computational QSAR models of novel
      bioassays for the prediction of IVRC results and compare with existing software.
      QSAR models were generated from existing Ames (n = 6512), Syrian Hamster
      Embryonic (SHE, n = 410), ISSCAN rodent carcinogenicity (ISC, n = 834) and
      GreenScreen GADD45a-GFP (n = 1415) chemical datasets. These models mapped the
      molecular descriptors of each compound to their respective assay result using
      machine learning algorithms (adaboost, k-Nearest Neighbours, C.45 Decision Tree,
      Multilayer Perceptron, Random Forest). The best performing models were combined
      with k-Nearest Neighbours to create a cascade model for IVRC prediction. High
      QSAR model performance was observed from ten time 10-fold cross-validation with
      above 80% accuracy and 0.85 AUC for each assay dataset. The cascade model
      predicted rat carcinogenicity with 69.3% accuracy and 0.700 AUC. This study
      demonstrates the novelty of a combined approach for IVRC prediction, with higher
      performance than existing software.

PMID- 29337193
TI  - IL-1beta augments H2S-induced increase in intracellular Ca2+ through polysulfides
      generated from H2S/NO interaction.
AB  - H2S has excitatory and inhibitory effects on Ca2+ signals via transient receptor
      potential ankyrin 1 (TRPA1) and ATP-sensitive K+ channels, respectively. H2S
      converts intracellularly to polysulfides, which are more potent agonists for
      TRPA1 than H2S. Under inflammatory conditions, changes in the expression and
      activity of these H2S target channels and/or the conversion of H2S to
      polysulfides may modulate H2S effects. Effects of proinflammatory cytokines on
      H2S-induced Ca2+ signals and polysulfide production in RIN14B cells were examined
      using fluorescence imaging with fura-2 and SSP4, respectively. Na2S, a H2S donor,
      induced 1) the inhibition of spontaneous Ca2+ signals, 2) inhibition followed by
      [Ca2+]i increase, and 3) rapid [Ca2+]i increase without inhibition in 50%
      (23/46), 22% (10/46), and 17% (8/46) of cells tested, respectively. IL-1beta
      augmented H2S-induced [Ca2+]i increases, which were inhibited by TRPA1 and
      voltage-dependent L-type Ca2+ channel blockers. However, IL-1beta treatment did
      not affect [Ca2+]i increases evoked by a TRPA1 agonist or high concentration of
      KCl. Na2S increased intracellular polysulfide levels, which were enhanced by IL
      1beta treatment. A NOS inhibitor suppressed the increased polysulfide production
      and [Ca2+]i increase in IL-1beta-treated cells. These results suggest that IL
      1beta augments H2S-induced [Ca2+]i increases via the conversion of H2S to
      polysulfides through NO synthesis, but not via changes in the activity and
      expression of target channels. Polysulfides may play an important role in the
      effects of H2S during inflammation.

PMID- 29337194
TI  - Fasudil ameliorates the ischemia/reperfusion oxidative injury in rat hearts
      through suppression of myosin regulatory light chain/NADPH oxidase 2 pathway.
AB  - Fasudil is a potent Rho-kinase (ROCK) inhibitor and can relax smooth muscle or
      cardiac muscle contraction through decreasing the phosphorylation level of myosin
      regulatory light chain (p-MLC20 or p-MLC2v), while p-MLC2v can function as a
      transcription factor to promote the NADPH oxidase 2 (NOX2) expression in rat
      hearts subjected to ischemia/reperfusion (I/R). This study aims to explore
      whether fasudil can protect the rat hearts against I/R oxidative injury through
      suppressing NOX2 expression via reduction of p-MLC2v level. The SD rat hearts
      were subjected to 1h-ischemia plus 3h-reperfusion, which showed myocardial
      injuries (myocardial fiber loss and disarray, increase of creatine kinase release
      and myocardial infarction/apoptosis), increase in ROCK activity and nuclear p
      MLC2v level concomitant with up-regulation of NOX2 and H2O2 production; these
      phenomena were attenuated by fasudil in a dose-dependent manner. Next, we
      verified the cardioprotective effect of fasudil and the underlying mechanisms in
      hypoxia-reoxygenation (H/R) -treated H9c2 cells. Consistent with the results in
      vivo, the H/R-treated H9c2 cells showed cellular injury (increase in apoptotic
      ratio), elevation in ROCK activity and nuclear p-MLC2v level, accompanied by up
      regulation of NOX2 and H2O2 production; these effects were blocked in the
      presence of fasudil in a dose-dependent way. Based on these observations, we
      conclude that beneficial effect of fasudil against myocardial I/R or H/R
      oxidative injury is related to the suppression of NOX2 expression through
      decrease of the p-MLC2v level. Our findings also highlight that intervention of
      MLC2v phosphorylation by drugs may provide a novel strategy to protect heart from
      I/R oxidative injury.

PMID- 29337195
TI  - Secretoneurin suppresses cardiac hypertrophy through suppression of oxidant
      stress.
AB  - The neuropeptide secretoneurin (SN) plays protective roles in myocardial
      ischemia. In the present study, the effect of SN in cardiac hypertrophy was
      investigated. We observed that, in isoproterenol (ISO) treatment induced cardiac
      or cardiomyocytes hypertrophy, a marked increase in the expression of endogenous
      SN in mouse plasma, myocardium and primary-cultured cardiomyocytes occurs. In
      hypertrophic mice, the heart size, heart weight/body weight (HW/BW) ratio,
      cardiomyocyte size, and atrial natriuretic peptide (ANP) and brain natriuretic
      peptide (BNP) expression were significantly higher than those in controls but
      were effectively suppressed by SN gene therapy. Similarly, the protective effects
      of SN were also observed in cultured cardiomyocytes following ISO treatment. SN
      significantly increased the activity of catalase and superoxide dismutase (SOD)
      in parallel with the decrease in reactive oxygen species levels in
      cardiomyocytes. We observed that SN evoked the activation of all of the AMPK,
      P38/MAPK and ERK/MAPK pathways in cardiomyocytes, but pretreatment with only AMPK
      inhibitor (compound C) and ERK1/2/MAPK inhibitor (PD98059) counteracted the
      protective effects of SN against cardiomyocyte hypertrophy and the suppressive
      effects of SN on oxidant stress in cardiomyocytes. These results indicated that
      endogenous SN is induced in hypertrophic cardiomyocytes, and may play a
      protective role in the pathogenesis of cardiac hypertrophy. These results suggest
      that exogenous SN supplementation protects the cardiac hypertrophy induced by ISO
      treatment through the activation of AMPK and ERK/MAPK pathways, thus upregulating
      antioxidants and suppressing oxidative stress.

PMID- 29337196
TI  - Nicorandil and theophylline can protect experimental rats against complete
      Freund's adjuvant-induced rheumatoid arthritis through modulation of
      JAK/STAT/RANKL signaling pathway.
AB  - Signaling pathways are interesting fields of study of pathogenesis and treatment
      trials. We elucidated the possible protective effects of nicorandil (15mg/kg/day)
      and theophylline (20mg/kg/day) on experimentally-induced RA, focusing on the role
      of JAK (Janus Kinase) / STAT (Signal Transducer and Activator of Transcription) /
      RANKL (Receptor Activator of Nuclear factor-Kappa B Ligand) / cytokine signaling
      pathway. Four sets of experiments were performed. First, effect of test agents on
      normal animals was evaluated. Second, effect of test agents was evaluated on
      Complete Freund's Adjuvant (CFA; 0.3ml, s.c.)-induced RA to investigate anti
      arthritic effect. Third, effect of test agents was evaluated on growth hormone
      (GH; 2mg/kg/day, s.c.)-induced stimulation of JAK/STAT/RANKL/cytokine signaling
      pathway to investigate the role of this signaling pathway in their anti-arthritic
      effect. Fourth, the effect of test agents was performed on CFA/GH-induced RA. To
      fulfill this purpose, serum anti-citrullinated peptide antibody (ACPA),
      interleukin-6 (IL-6), and cartilage oligomeric matrix protein (COMP), together
      with tissue JAK2, STAT3, RANKL, inducible and endothelial nitric oxide synthases
      (iNOS and eNOS) as well as macrophage inflammatory protein (MIP1alpha) were
      estimated using ELISA, Western blotting and PCR techniques, confirmed by a
      histopathological study. Test agents significantly corrected JAK2, STAT3, RANKL
      and IL-6 values in animals receiving GH. Additionally, test agents could correct
      ACPA, IL-6, COMP, JAK2, STAT3, RANKL, iNOS, eNOS and MIP1alpha levels compared
      with the respective CFA or CFA/GH controls. These results conclude that
      nicorandil and theophylline have good anti-arthritic effects related to
      modulation of JAK/STAT/RANKL signaling pathway. Further clinical trials are
      claimed.

PMID- 29337197
TI  - Brain perfusion alterations in tick-borne encephalitis-preliminary report.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) changes in tick-borne encephalitis
      (TBE) are non-specific and the pathophysiological mechanisms leading to their
      formation remain unclear. This study investigated brain perfusion in TBE patients
      using dynamic susceptibility-weighted contrast-enhanced magnetic resonance
      perfusion imaging (DSC-MRI perfusion). METHODS: MRI scans were performed for 12
      patients in the acute phase, 3-5days after the diagnosis of TBE. Conventional MRI
      and DSC-MRI perfusion studies were performed. Cerebral blood flow (CBF), cerebral
      blood volume (CBV), mean transit time (MTT), and time to peak (TTP) parametric
      maps were created. The bilateral frontal, parietal, and temporal subcortical
      regions and thalamus were selected as regions of interest. Perfusion parameters
      of TBE patients were compared to those of a control group. RESULTS: There was a
      slight increase in CBF and CBV, with significant prolongation of TTP in
      subcortical areas in the study subjects, while MTT values were comparable to
      those of the control group. A significant increase in thalamic CBF (p<0.001) and
      increased CBV (p<0.05) were observed. Increased TTP and a slight reduction in MTT
      were also observed within this area. CONCLUSIONS: The DSC-MRI perfusion study
      showed that TBE patients had brain perfusion disturbances, expressed mainly in
      the thalami. These results suggest that DSC-MRI perfusion may provide important
      information regarding the areas affected in TBE patients.

PMID- 29337198
TI  - Comparison of untagged and his-tagged dihydrodipicolinate synthase from the
      enteric pathogen Vibrio cholerae.
AB  - Given the emergence of multi drug resistant Vibrio cholerae strains, there is an
      urgent need to characterize new anti-cholera targets. One such target is the
      enzyme dihydrodipicolinate synthase (DHDPS; EC 4.3.3.7), which catalyzes the
      first committed step in the diaminopimelate pathway. This pathway is responsible
      for the production of two key metabolites in bacteria and plants, namely meso-2,6
      diaminopimelate and L-lysine. Here, we report the cloning, expression and
      purification of untagged and His-tagged recombinant DHDPS from V. cholerae (Vc
      DHDPS) and provide comparative structural and kinetic analyses. Structural
      studies employing circular dichroism spectroscopy and analytical
      ultracentrifugation demonstrate that the recombinant enzymes are folded and exist
      as dimers in solution. Kinetic analyses of untagged and His-tagged Vc-DHDPS show
      that the enzymes are functional with specific activities of 75.6 U/mg and 112
      U/mg, KM (pyruvate) of 0.14 mM and 0.15 mM, KM (L-aspartate-4-semialdehyde) of
      0.08 mM and 0.09 mM, and kcat of 34 and 46 s-1, respectively. These results
      demonstrate there are no significant changes in the structure and function of Vc
      DHDPS upon the addition of an N-terminal His tag and, hence, the tagged
      recombinant product is suitable for future studies, including screening for new
      inhibitors as potential anti-cholera agents. Additionally, a polyclonal antibody
      raised against untagged Vc-DHDPS is validated for specifically detecting
      recombinant and native forms of the enzyme.

PMID- 29337199
TI  - Designing an intuitive web application for drug discovery scientists.
AB  - We discuss how we designed the Open Targets Platform (www.targetvalidation.org),
      an intuitive application for bench scientists working in early drug discovery. To
      meet the needs of our users, we applied lean user experience (UX) design methods:
      we started engaging with users very early and carried out research, design and
      evaluation activities within an iterative development process. We also emphasize
      the collaborative nature of applying lean UX design, which we believe is a
      foundation for success in this and many other scientific projects.

PMID- 29337200
TI  - Mimicking the 3D biology of osteochondral tissue with microfluidic-based
      solutions: breakthroughs towards boosting drug testing and discovery.
AB  - The development of tissue-engineering (TE) solutions for osteochondral (OC)
      regeneration has been slowed by technical hurdles related to the recapitulation
      of their complex and hierarchical architecture. OC defects refer to damage of
      both the articular cartilage and the underlying subchondral bone. To repair an OC
      tissue defect, the complexity of the bone and cartilage must be considered. To
      help achieve this, microfluidics is converging with TE approaches to provide new
      treatment possibilities. Microfluidics uses precise micrometer-to-millimeter
      scale fluid flows to achieve high-resolution and spatial and/or temporal control
      of the cell microenvironment, providing powerful tools for cell culturing.
      Herein, we overview the progress of microfluidics for developing 3D in vitro
      models of OC tissue, with a focus on cancer bone metastasis.

PMID- 29337201
TI  - On the glycosylation aspects of biosimilarity.
AB  - The recent expiration of several protein therapeutics opened the door for
      biosimilar development. Biosimilars are biologic medical products that are
      similar but not identical copies of already-authorized protein therapeutics.
      Critical quality attributes (CQA), such as post-translational modifications of
      recombinant biotherapeutics, are important for the clinical efficacy and safety
      of both the innovative biologics and their biosimilar counterparts. Here, we
      summarize biosimilarity CQAs, considering the regulatory guidelines and the
      statistical aspects (e.g., biosimilarity index) and then discuss glycosylation as
      one of the important attributes of biosimilarity. Finally, we introduced the
      'Glycosimilarity Index', which is based on the averaged biosimilarity criterion.

PMID- 29337202
TI  - Progress with covalent small-molecule kinase inhibitors.
AB  - With reduced risk of toxicity and high selectivity, covalent small-molecule
      kinase inhibitors (CSKIs) have emerged rapidly. Through the lens of structural
      system pharmacology, here we review this rapid progress by considering design
      strategies and the challenges and opportunities offered by current CSKIs.

PMID- 29337203
TI  - Stem cells as vehicles and targets of nanoparticles.
AB  - Modulation of endogenous adult stem cell niches represents a promising strategy
      for regeneration of tissues and to correct cell abnormalities, including cancer.
      Recent advances show the possibility to target endogenous stem cells or their
      progenies by using nanoparticles conjugated with specific biomolecules. In
      addition, the targeting of the stem cell niche can be accomplished by using stem
      cells loaded with nanoparticles. This review examines principles for the
      targeting of endogenous stem cells as well as factors for the modulation of stem
      cells.

PMID- 29337204
TI  - The positive impacts of Real-World Data on the challenges facing the evolution of
      biopharma.
AB  - Demand for healthcare services is unprecedented. Society is struggling to afford
      the cost. Pricing of biopharmaceutical products is under scrutiny, especially by
      payers and Health Technology Assessment agencies. As we discuss here, rapidly
      advancing technologies, such as Real-World Data (RWD), are being utilized to
      increase understanding of disease. RWD, when captured and analyzed, produces the
      Real-World Evidence (RWE) that underpins the economic case for innovative
      medicines. Furthermore, RWD can inform the understanding of disease, help
      identify new therapeutic intervention points, and improve the efficiency of
      research and development (R&D), especially clinical trials. Pursuing
      precompetitive collaborations to define shared requirements for the use of RWD
      would equip service-providers with the specifications needed to implement cloud
      based solutions for RWD acquisition, management and analysis. Only this approach
      would deliver cost-effective solutions to an industry-wide problem.

PMID- 29337205
TI  - Increasing mtDNA levels as therapy for mitochondrial optic neuropathies.
AB  - Leber hereditary optic neuropathy (LHON) is a rare, inherited mitochondrial
      disease. No treatment has shown a clear-cut benefit on a clinically meaningful
      end-point. Primary open-angle glaucoma (POAG) is a frequent, acquired optic
      neuropathy. Lowering intraocular pressure (IOP) reduces disease progression.
      However, current methods to decelerate this progression are recognized as being
      inadequate. Therefore, there is a clear need to look for new therapeutic
      approaches. The growing evidence indicates that POAG can also be a mitochondrial
      optic neuropathy (MON). Several risk elements are common for both diseases and
      all of them decrease mitochondrial (mt)DNA content. Based on these susceptibility
      factors and their molecular mechanism, we suggest herein pharmacological
      therapies targeted to increase mtDNA levels, oxidative phosphorylation (OXPHOS)
      capability, and mitochondrial energy production as treatments for MONs.

PMID- 29337206
TI  - Evolution of the POU1F1 transcription factor in mammals: Rapid change of the
      alternatively-spliced beta-domain.
AB  - The POU1F1 (Pit-1) transcription factor is important in regulating expression of
      growth hormone, prolactin and TSH beta-subunit, and controlling development of
      the anterior pituitary cells in which these hormones are produced. POU1F1 is a
      conserved protein comprising three main domains, an N-terminal transcription
      activation domain (TAD), a POU-specific domain and a C-terminal homeodomain.
      Within the TAD, a beta-domain can be inserted by alternative splicing, giving an
      extended 'beta-variant' with altered properties. Here sequence data from over 100
      species were used to assess the variability of POU1F1 in mammals. This showed
      that the POU-specific domain and homeodomain are very strongly conserved, and
      that the TAD is somewhat less conserved, as are linker and hinge regions between
      these main domains. On the other hand, the beta-domain is very variable,
      apparently evolving at a rate not significantly different from that expected for
      unconstrained, neutral evolution. In several species stop and/or frameshift
      mutations within the beta-domain would prevent expression of the beta-variant as
      a functional protein. In most species expression of the beta-variant is low (<5%
      of total POU1F1 expression). The rate of evolution of POU1F1 in mammals shows
      little variation, though the lineage leading to dog does show an episode of
      accelerated change. This comparative genomics study suggests that in most
      mammalian species POU1F1 variants produced by alternative splicing may have
      little physiological significance.

PMID- 29337207
TI  - Intrasexual competition mediates the relationship between men's testosterone and
      mate retention behavior.
AB  - Previous research has established a link between testosterone concentrations in
      males and their mating effort as it relates to their mate seeking behaviors.
      However, very little research has analyzed how variability in basal testosterone
      concentration of males affects their mating effort once they have secured a
      romantic partner. In a sample of undergraduate men, the relationship between
      testosterone, intrasexual competitiveness, and mate retention behavior was
      examined. Results showed that higher basal testosterone predicted more self
      reported mate retention effort. This relationship was mediated by intrasexual
      competitiveness, such that high T men reported more intrasexual competitiveness,
      which when included in the model predicted mate retention, and reduced the
      initial T - mate retention relationship to statistical non-significance. When
      examined separately, this mediation effect applied specifically to cost
      inflicting, rather than benefit-provisioning, mate retention behavior. These are
      the first findings to link T to mate retention effort and to identify intrasexual
      competitiveness as a mechanism which might account for this relationship.

PMID- 29337208
TI  - Quantum Mechanics predicts evolutionary biology.
AB  - Nowhere are the shortcomings of conventional descriptive biology more evident
      than in the literature on Quantum Biology. In the on-going effort to apply
      Quantum Mechanics to evolutionary biology, merging Quantum Mechanics with the
      fundamentals of evolution as the First Principles of Physiology-namely
      negentropy, chemiosmosis and homeostasis-offers an authentic opportunity to
      understand how and why physics constitutes the basic principles of biology.
      Negentropy and chemiosmosis confer determinism on the unicell, whereas
      homeostasis constitutes Free Will because it offers a probabilistic range of
      physiologic set points. Similarly, on this basis several principles of Quantum
      Mechanics also apply directly to biology. The Pauli Exclusion Principle is both
      deterministic and probabilistic, whereas non-localization and the Heisenberg
      Uncertainty Principle are both probabilistic, providing the long-sought after
      ontologic and causal continuum from physics to biology and evolution as the
      holistic integration recognized as consciousness for the first time.

PMID- 29337209
TI  - The role of d-allo-isoleucine in the deposition of the anti-Leishmania peptide
      bombinin H4 as revealed by 31P solid-state NMR, VCD spectroscopy, and MD
      simulation.
AB  - Bombinin H4 is an antimicrobial peptide that was isolated from the toad Bombina
      variegata. Bombinin H family peptides are active against gram-positive, gram
      negative bacteria, and fungi as well as the parasite Leishmania. Among them,
      bombinin H4 (H4), which contains d-allo-isoleucine (d-allo-Ile) as the second
      residue in its sequence, is the most active, and its l-isomer is bombinin H2
      (H2). H4 has a significantly lower LC50 than H2 against Leishmania. However, the
      atomic-level mechanism of the membrane interaction and higher activity of H4 has
      not been clarified. In this work, we investigated the behavior of the
      conformations and interactions of H2 and H4 with the Leishmania membrane using
      31P solid-state nuclear magnetic resonance (NMR), vibrational circular dichroism
      (VCD) spectroscopy, and molecular dynamics (MD) simulations. The generation of
      isotropic 31P NMR signals depending on the peptide concentration indicated the
      abilities of H2 and H4 to exert antimicrobial activity via membrane disruption.
      The VCD experiment and density functional theory calculation confirmed the
      different stability and conformations of the N-termini of H2 and H4. MD
      simulations revealed that the N-terminus of H4 is more stable than that of H2 in
      the membrane, in line with the VCD experiment data. VCD and MD analyses
      demonstrated that the first l-Ile and second d-allo-Ile of H4 tend to take a cis
      conformation. These residues function as an anchor and facilitate the easy
      winding of the helical conformation of H4 in the membrane. It may assist to
      quickly reach to the threshold concentration of H4 on the Leishmania membrane.
      This article is part of a Special Issue entitled: d-Amino acids: biology in the
      mirror, edited by Dr. Loredano Pollegioni, Dr. Jean-Pierre Mothet and Dr. Molla
      Gianluca.

PMID- 29337210
TI  - Rate of Urologic Injury with Robotic Hysterectomy.
AB  - STUDY OBJECTIVE: To evaluate rates of urologic injury in patients who underwent
      robotic hysterectomy compared with laparoscopic, vaginal, and open hysterectomy.
      DESIGN: A retrospective analysis (Canadian Task Force classification II-2).
      SETTING: Henry Ford Health System, 2013 to 2016. PATIENTS: Women who underwent
      robotic, vaginal, laparoscopic, and open abdominal hysterectomy. INTERVENTIONS:
      Robotic hysterectomy, laparoscopic-assisted vaginal hysterectomy, total
      laparoscopic hysterectomy, laparoscopic supracervical hysterectomy, vaginal
      hysterectomy, and abdominal hysterectomy. MEASUREMENTS AND MAIN RESULTS: To
      identify patients with urologic injury, a departmental database for quality
      improvement was searched for reported urologic injuries. In addition, patients
      who had urology consultation within 90 days of hysterectomy were screened for
      injury. A total of 3114 hysterectomies were identified by retrospective chart
      review. One thousand eighty-eight robotic, 782 laparoscopic, 304 vaginal, and 940
      abdominal hysterectomies were analyzed for urologic complications. A total of 27
      injuries were confirmed (7 during laparoscopic hysterectomy, 10 during robotic
      hysterectomy, 1 during vaginal hysterectomy, and 9 during abdominal
      hysterectomy). The overall rate of urologic injury was 0.87% with a 0.55% risk of
      bladder injury and a 0.32% risk of injury to the ureter. When the route of
      hysterectomy was taken into account, the risk of urologic injury was 0.92% for
      robotic hysterectomy, 0.90% for laparoscopic hysterectomy, 0.33% for vaginal
      hysterectomy, and 0.96% for open hysterectomy. The mean body mass index (BMI) for
      all patients was 32.7 kg/m2; injured patients had a mean BMI of 34.6 kg/m2, and
      noninjured patients had a mean BMI of 32.0 kg/m2 (p = .10). CONCLUSION: Rates of
      urologic injury with robotic hysterectomy are similar to those of laparoscopic
      hysterectomy in our population. BMI was not significantly different in patients
      who had urologic injuries. Surgeon volume was not associated with risk for
      urologic injury.

PMID- 29337211
TI  - Extraperitoneal Para-Aortic Lymphadenectomy by Robot-Assisted Laparoscopy.
AB  - STUDY OBJECTIVE: To evaluate the outcomes of extraperitoneal para-aortic
      lymphadenectomy by robot-assisted laparoscopy. DESIGN: A retrospective study
      (Canadian Task Force classification III). SETTING: An academic institution.
      PATIENTS: Twenty-three consecutive patients with gynecologic cancer who presented
      for para-aortic lymphadenectomy between March 2016 and May 2017 were reviewed
      retrospectively. INTERVENTIONS: Extraperitoneal para-aortic lymphadenectomy by
      robot-assisted laparoscopy was performed. MEASUREMENTS AND MAIN RESULTS: Of the
      23 patients reviewed retrospectively, 10 had cervical cancer, 7 had endometrial
      cancer, 5 had adnexal cancer, and 1 had vaginal cancer. Data regarding patient
      characteristics, indication for para-aortic lymphadenectomy, type of surgery
      (infrarenal or inframesenteric), operative time, surgical complications, number
      of nodes retrieved, and postoperative hospital length of stay were collected. Two
      patients were excluded because of early perforation of the peritoneum. In total,
      21 para-aortic lymphadenectomies were performed (16 infrarenal and 5
      inframesenteric). The median skin-to-skin operating time of infrarenal
      extraperitoneal para-aortic lymphadenectomy by robot-assisted laparoscopy was 170
      minutes (range, 90-225 minutes), the median lymph node count was 18 (range, 11
      38), and the median estimated blood loss was 50 mL (range, 10-600 mL). The median
      skin-to-skin operating time of inframesenteric extraperitoneal para-aortic
      lymphadenectomy by robot-assisted laparoscopy was 120 minutes (range, 90-220
      minutes), the median lymph node count was 10 (range, 7-19), and the median
      estimated blood loss was 30 mL (range, 10-100). Intraoperative complications
      included 1 thermal lesion of the left genitofemoral nerve, 1 thermal lesion of
      the left mesoureter (a ureteral stent was placed to avoid ureteric necrosis and
      fistula without after effect), and 1 lesion of the inferior vena cava that was
      sutured by robot-assisted laparoscopy. There were 2 additional cases of
      perforation of the peritoneum that occurred in the infrarenal group. The median
      hospital length of stay was 1 day (range, 0-7 days). Three patients were
      readmitted for symptomatic lymphocysts. CONCLUSION: Extraperitoneal para-aortic
      lymphadenectomy by robot-assisted laparoscopy provides good visualization of the
      operative field without arm conflict. Still, perforation of the peritoneum and
      symptomatic lymphocysts are a postoperative concern.

PMID- 29337212
TI  - Successful Management of Heterotopic Intramural Pregnancy Leading to a Live Birth
      of the Intrauterine Pregnancy.

PMID- 29337214
TI  - Correction.

PMID- 29337213
TI  - Military Surgeon Volume and Stress Incontinence Surgery Complications: A
      Retrospective Cohort Study.
AB  - STUDY OBJECTIVE: To compare 12-month postoperative complication rates in women
      who underwent sling procedures by high-volume versus low-volume surgeons at US
      military treatment facilities (MTFs). DESIGN: Retrospective cohort study
      (Canadian Task Force classification II-2). SETTING: US MTFs. PATIENTS: Female
      military beneficiaries enrolled in TRICARE. INTERVENTIONS: Sling surgery for
      stress urinary incontinence between January 1, 2011 and December 31, 2012.
      MEASUREMENTS AND MAIN RESULTS: The primary exposure was surgeon volume (high vs
      low). Surgeon volume was categorized as high or low based on the number of slings
      performed in the previous 2 years at US MTFs (January 1, 2009 to December 31,
      2010). The primary outcome was a composite variable indicating at least 1
      postoperative complication within 12 months. We used International Classification
      of Diseases, 9th revision and Current Procedural Terminology codes to identify
      postoperative complications that occurred in the 12 months after the index sling
      procedure. During the study period 348 gynecologic and urologic surgeons
      performed 1632 slings. The average patient age was 47.2 years. Based on our data
      distribution we classified surgeons as high volume (>12 slings/2 years) or low
      volume (<4 slings/2 years). High-volume surgeons operated on patients who were
      older, more likely to have comorbidities, and more likely to receive concomitant
      prolapse surgery. Using a cluster analysis the overall likelihood of at least 1
      postoperative complication in 12 months for high-volume versus low-volume
      surgeons was 48.4% versus 42.2% (adjusted odds ratio, 1.24; 95% confidence
      interval, .99-1.54; p = .06). There were no differences between high- and low
      volume surgeons in the rate of almost all other postoperative complications.
      CONCLUSION: No significant differences in 12-month complication rates after sling
      surgery, stratified by surgeon volume, were seen in a setting of overall low
      volume military surgeons.

PMID- 29337215
TI  - Anti-angiogenic effects of Qingdu granule on breast cancer through inhibiting
      NFAT signaling pathway.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Qingdu granule (QDG), a traditional Chinese
      herbal prescription, had anti-tumor effect on breast cancer. However the
      underlying mechanism of QDG was unclear. THE AIM OF THIS STUDY: The present study
      aimed to investigate whether QDG could inhibit angiogenesis of breast cancer via
      acting on nuclear factor of activated T-cells (NFAT) signaling pathway. This was
      implicated in human umbilical vein endothelial cells (HUVECs) in vitro and breast
      cancer xenograft model in vivo. MATERIALS AND METHODS: The VEGF165 (15.58 ng/mL)
      induced human umbilical vein endothelial cells (HUVECs) were treated with serum
      samples containing tamoxifen (TAM), tacrolimus (FK506), or QDG with three
      dosages. The migration and canalization capacities of HUVECs were evaluated by
      transwell migration and tube formation assay. In 72 h-cultured HUVECs, The gene
      expression, protein amount, and nuclear translocation of NFATc3 were measured.
      The anti-tumor and anti-angiogenic effects of QDG in vivo were investigated in
      breast cancer xenograft model. The serum VEGF levels, microvessel density, and
      protein expressions (immunohistochemistry and western blot) of VEGF, VEGFR2 and
      NFATc3 were detected. RESULTS: The results showed that, QDG significantly
      inhibited HUVEC migration and tube formation. It downregulated NFATc3 gene
      expression, decreased NFATc3 protein amount, and reduced the ratio of NFATc3
      nuclear translocation in HUVECs. In breast cancer xenograft model, QDG treatment
      significantly suppressed tumor growth, inhibited VEGF release, and decreased
      microvessel density. QDG reduced protein expressions of VEGF, VEGFR2 and NFATc3.
      CONCLUSION: The results suggested that QDG showed anti-angiogenic effects of
      breast cancer both in vitro and in vivo. The mechanism might be partially
      associated with inhibiting NFAT signaling pathway.

PMID- 29337216
TI  - In vitro lung epithelial cell transport and anti-interleukin-8 releasing activity
      of liposomal ciprofloxacin.
AB  - As a promising long-acting inhaled formulation, liposomal ciprofloxacin (Lipo
      CPFX) was characterized in the in vitro human lung epithelial Calu-3 cell
      monolayer system, compared to ciprofloxacin in solution (CPFX). Its modulated
      absorptive transport and uptake, and sustained inhibitory activity against
      induced pro-inflammatory interleukin-8 (IL-8) release were examined. The
      absorptive transport and uptake kinetics for Lipo-CPFX and CPFX were determined
      at 0.1-50 mg/ml in the Transwell system. The Lipo-CPFX transport was then
      challenged for mechanistic exploration via cell energy depletion, a reduced
      temperature, endocytosis and/or lipid fusion inhibition, and addition of excess
      non-loaded liposomes. The inhibitory activities of Lipo-CPFX and CPFX against
      lipopolysaccharide (LPS)-induced IL-8 release were assessed in a co-incubation or
      pre-incubation mode. In the tight Calu-3 cell monolayers, Lipo-CPFX yielded 15
      times slower ciprofloxacin flux of absorptive transport and 5-times lower
      cellular drug uptake than CPFX. Its transport appeared to be transcellular;
      kinetically linear, proportional to encapsulated ciprofloxacin concentration; and
      consistent with the cell energy-independent lipid bilayer fusion mechanism. Lipo
      CPFX was equipotent to CPFX in the anti-IL-8 releasing activity upon 24 h co
      incubation with LPS. Additionally, Lipo-CPFX, but not CPFX, retained the anti-IL
      8 releasing activity even 24 h after pre-incubation. In conclusion, Lipo-CPFX
      enabled slower absorptive lung epithelial cell transport and uptake of
      ciprofloxacin, apparently via the lipid bilayer fusion mechanism, and the
      sustained inhibitory activity against LPS-induced IL-8 release, compared to CPFX.

PMID- 29337217
TI  - Peptide drug stability: The anti-inflammatory drugs Pep19-2.5 and Pep19-4LF in
      cream formulation.
AB  - In previous years, we developed anti-infective drugs based on antimicrobial
      peptides (AMPs), which have been shown to effectively block severe infections and
      inflammation in vitro as well as in vivo. Besides systemic application, the
      occurrence of severe local infections necessitates a topical application for
      example in the case of severe skin and soft tissue infections (SSTI). Recent
      investigations show that the synthetic anti-lipopolysaccharide peptide (SALP)
      Pep19-2.5 (Aspidasept(r) I) and a variant called Pep19-4LF (Aspidasept(r) II) are
      able to supress inflammation reactions also in keratinocytes, Langerhans cells,
      and dendritic cells from the skin. For topical application, a possible
      formulation represents the drug dispersed into a pharmaceutical cream (DAC base
      cream). Here, we present investigations on the stability of the peptides using
      this formulation in dependence on time, which includes the evaluation of the
      extraction procedure, the quantitative analysis of the peptides after extraction,
      its sensitivity to protease degradation and its ability to maintain activity
      against LPS-induced inflammation in vitro. We have developed an extraction
      procedure for the peptides with an optimum yield and showed that Pep19-2.5 is
      present as a dimer after extraction from the cream, whereas Pep19-4LF retains its
      monomeric form. Both peptides show no degradation by chymotrypsin after
      extraction for at least 1 h, which is indicative for an attachment of
      constituents of the base cream, inhibiting the cutting into peptidic part
      structures. The extracted peptides and in particular the dimeric Pep19-2.5 are
      still able to inhibit the LPS-induced inflammation reaction in human mononuclear
      cells.

PMID- 29337219
TI  - Citrus bioflavonoid, hesperetin, as inhibitor of two thrombin-like snake venom
      serine proteases isolated from Crotalus simus.
AB  - Around 5.5 million people suffer from snakebites per year, with about 400,000
      cases with some type of sequelae, such as amputation, and 20,000 to 125,000 cases
      with the fatal end. Usually, the victim outcome depends on correct, agile and
      many times in situ intervention based on the proper identification of the snake
      venom type and its potential effects, among other factors. Therefore, knowledge
      on the snake venom composition and a research on inhibitors of snake venom target
      components might ameliorate envenoming dangerous outcome. Herein, two thrombin
      like serine proteases from the Crotalus simus snake venom - SVSP1 and SVSP2 -
      were isolated in two chromatographic steps, using gel filtration and then RP
      HPLC. They showed molecular masses of around 31.3 and 24.6 kDa, respectively, and
      mostly beta-sheet secondary structure features. The SVSP1 and SVSP2 were
      sequenced using tandem mass spectrometry (Q-TOF). Using the known serine protease
      structure (PDB entry: 4e7n), which was evaluated as homologous to the two target
      proteins, in silico docking results showed that hesperetin is its excellent
      inhibitor. Using in vitro tests with the commercial hesperetin, kinetic
      parameters were obtained for SVSPs against the synthetic substrate BApNA.
      Obtained results pointed that hesperetin might act as an uncompetitive (SVSP1) or
      mixed (SVSP2) inhibitor. Also, the fluorescence quenching upon inhibition was
      observed, as well as, red shift in maximums of around 20 nm, which indicate that
      the tryptophan residues in the target enzymes suffered conformational changes
      caused by hesperetin binding. Thus, a naturally occurring flavone that can easily
      be extracted from oranges might serve as low-cost inhibitor of the investigated
      snake venom proteases.

PMID- 29337218
TI  - Calcium-dependent disorder-to-order transitions are central to the secretion and
      folding of the CyaA toxin of Bordetella pertussis, the causative agent of
      whooping cough.
AB  - The adenylate cyclase toxin (CyaA) plays an essential role in the early stages of
      respiratory tract colonization by Bordetella pertussis, the causative agent of
      whooping cough. Once secreted, CyaA invades eukaryotic cells, leading to cell
      death. The cell intoxication process involves a unique mechanism of translocation
      of the CyaA catalytic domain directly across the plasma membrane of the target
      cell. Herein, we review our recent results describing how calcium is involved in
      several steps of this intoxication process. In conditions mimicking the low
      calcium environment of the crowded bacterial cytosol, we show that the C
      terminal, calcium-binding Repeat-in-ToXin (RTX) domain of CyaA, RD, is an
      extended, intrinsically disordered polypeptide chain with a significant level of
      local, secondary structure elements, appropriately sized for transport through
      the narrow channel of the secretion system. Upon secretion, the high calcium
      concentration in the extracellular milieu induces the refolding of RD, which
      likely acts as a scaffold to favor the refolding of the upstream domains of the
      full-length protein. Due to the presence of hydrophobic regions, CyaA is prone to
      aggregate into multimeric forms in vitro, in the absence of a chaotropic agent.
      We have recently defined the experimental conditions required for CyaA folding,
      comprising both calcium binding and molecular confinement. These parameters are
      critical for CyaA folding into a stable, monomeric and functional form. The
      monomeric, calcium-loaded (holo) toxin exhibits efficient liposome
      permeabilization and hemolytic activities in vitro, even in a fully calcium-free
      environment. By contrast, the toxin requires sub-millimolar calcium
      concentrations in solution to translocate its catalytic domain across the plasma
      membrane, indicating that free calcium in solution is actively involved in the
      CyaA toxin translocation process. Overall, this data demonstrates the remarkable
      adaptation of bacterial RTX toxins to the diversity of calcium concentrations it
      is exposed to in the successive environments encountered in the course of the
      intoxication process.

PMID- 29337220
TI  - BotAF, a new Buthus occitanus tunetanus scorpion toxin, produces potent analgesia
      in rodents.
AB  - This work reports the purification of new potent scorpion neuropeptide, named
      BotAF, by an activity-guided screening approach. BotAF is a 64-residue long-chain
      peptide that shares very high similarity with the original beta-like scorpion
      toxin group, in which several peptides have been characterized to be anti
      nociceptive in rodents. BotAF administration to rodents does not produce any
      toxicity or motor impairment, including at high doses. In all models
      investigated, BotAF turned out to be an efficient peptide in abolishing acute and
      inflammatory (both somatic and visceral) pain in rodents. It performs with high
      potency compared to standard analgesics tested in the same conditions. The anti
      nociceptive activity of BotAF depends on the route of injection: it is inactive
      when tested by i.c.v. or i.v. routes but gains in potency when pre-injected
      locally (in the same compartment than the irritant itself) or by i.t. root 40 to
      60 min before pain induction, respectively. BotAF is not an AINS-like compound as
      it fails to reduce inflammatory edema. Also, it does not activate the opioidergic
      system as its activity is not affected by naloxone. BotAF does also not bind onto
      RyR and has low activity towards DRG ion channels (particularly TTX sensitive Na+
      channels) and does not bind onto rat brain synaptosome receptors. In somatic and
      visceral pain models, BotAF dose-dependently inhibited lumbar spinal cord c-fos/c
      jun mRNA up regulation. Altogether, our data favor a spinal or peripheral anti
      nociceptive mode of action of BotAF.

PMID- 29337221
TI  - Venom characterization of the Amazonian scorpion Tityus metuendus.
AB  - The soluble venom from the scorpion Tityus metuendus was characterized by various
      methods. In vivo experiments with mice showed that it is lethal. Extended
      electrophysiological recordings using seven sub-types of human voltage gated
      sodium channels (hNav1.1 to 1.7) showed that it contains both alpha- and beta
      scorpion toxin types. Fingerprint analysis by mass spectrometry identified over
      200 distinct molecular mass components. At least 60 sub-fractions were recovered
      from HPLC separation. Five purified peptides were sequenced by Edman degradation,
      and their complete primary structures were determined. Additionally, three other
      peptides have had their N-terminal amino acid sequences determined by Edman
      degradation and reported. Mass spectrometry analysis of tryptic digestion of the
      soluble venom permitted the identification of the amino acid sequence of 111
      different peptides. Search for similarities of the sequences found indicated that
      they probably are: sodium and potassium channel toxins, metalloproteinases,
      hyaluronidases, endothelin and angiotensin-converting enzymes, bradykinin
      potentiating peptide, hypothetical proteins, allergens, other enzymes, other
      proteins and peptides.

PMID- 29337222
TI  - Blockade of placental growth factor reduces vaso-occlusive complications in
      murine models of sickle cell disease.
AB  - Vaso-occlusive crisis (VOC) is the most common and debilitating complication of
      sickle cell disease (SCD); recurrent episodes cause organ damage and contribute
      to early mortality. Plasma placental growth factor (PlGF) levels are elevated in
      SCD and can further increase under hypoxic conditions in SCD mice. Treatment with
      a PlGF-neutralizing antibody (anti-PlGF Ab) in SCD mice reduced levels of
      monocyte chemoattractant protein-3, eotaxin, macrophage colony-stimulating
      factor, and plasminogen activator inhibitor-1 significantly, and of macrophage
      derived chemokine and macrophage inflammatory protein-3beta moderately; this may
      contribute to inhibition of leukocyte recruitment, activation, and thrombosis. In
      subsequent experiments, anti-PlGF Ab treatment significantly reduced plasma
      lactate dehydrogenase levels, indicating possible reduction in cellular
      destruction and/or hemolysis. Histopathology studies revealed decreased incidence
      and severity of congestion in the lungs and spleen with repeated anti-PlGF Ab
      treatment. Furthermore, anti-PlGF Ab significantly reduced vaso-occlusion events
      under hypoxic conditions in a modified dorsal skinfold chamber model in SCD mice.
      Therefore, elevated PlGF levels may contribute to recruitment and activation of
      leukocytes. This can subsequently lead to increased pathology of affected organs
      in addition to mediating acute hypoxia/reoxygenation-triggered vaso-occlusion
      under SCD conditions. Thus, targeting PlGF may offer a therapeutic approach to
      reduce acute VOC and possibly alleviate long-term vascular complications in
      patients with SCD.

PMID- 29337223
TI  - Sequential Conditioning with Thiotepa in T Cell- Replete Hematopoietic Stem Cell
      Transplantation for the Treatment of Refractory Hematologic Malignancies:
      Comparison with Matched Related, Haplo-Mismatched, and Unrelated Donors.
AB  - The results of conventional allogeneic stem cell transplantation (SCT) in
      refractory hematologic malignancies are poor. Sequential strategies have shown
      promising results in refractory acute myelogenous leukemia (AML), but have not
      been validated in a haploidentical (Haplo) transplant setting. We have developed
      a new sequential approach combining chemotherapy with broad antitumor activity
      (thiotepa 10 mg/kg, etoposide 400 mg/m2, and cyclophosphamide 1600 mg/m2 from day
      -15 to day -10), followed after 3 days of rest by a reduced-intensity
      conditioning regimen (fludarabine 150 mg/m2, i.v. busulfan 6.4 mg/kg, and
      thymoglobulin 5 mg/kg from day -6 to day -2). High-dose post-transplantation
      cyclophosphamide was added in cases with Haplo donors. Seventy-two patients
      (median age, 54 years) with a refractory hematologic malignancy (44 with acute
      myelogenous leukemia, 7 with acute lymphoblastic leukemia, 15 with
      myelodysplastic syndrome/myeloproliferative neoplasms, and 6 with lymphomas) were
      included in this retrospective multicenter study. Donors were Haplo (n = 27),
      matched related (MRD; n = 16), and unrelated (UD; n = 29). With a median follow
      up of 21 months, the 2-year overall survival (OS) and event-free survival (EFS)
      were 54.7% and 49.3%, respectively, in recipients of Haplo transplants, 49.2% and
      43.8%, respectively, in recipients of MRD transplants, and 37.9% and 28%,
      respectively, in recipients of UD transplants. Compared with UD, the outcomes
      were improved in Haplo in terms of the incidences of acute grade II-IV graft
      versus-host disease (GVHD) (11.1% versus 41.4%; P < .001) and GVHD-free, relapse
      free survival (44.4 versus 10.3%; P = .022). These results support the safety and
      efficacy of a thiotepa-based sequential approach in allogeneic SCT with a Haplo
      donor with post-transplantation immune modulation. Thus, in patients with
      refractory hematologic malignancies, there seems to be no benefit in searching
      for a UD when a Haplo donor is readily available.

PMID- 29337224
TI  - An experimental study for rapid detection and quantification of endodontic
      microbiota following photo-activated disinfection via new multiplex real-time PCR
      assay.
AB  - BACKGROUND: The infected root canal system harbors one of the highest
      accumulations of polymicrobial infections. Since the eradication of
      endopathogenic microbiota is a major goal in endodontic infection therapy, photo
      activated disinfection (PAD) can be used as an alternative therapeutic method in
      endodontic treatment. Compared to cultivation-based approaches, molecular
      techniques are more reliable for identifying microbial agents associated with
      endodontic infections. The purpose of this study was to evaluate the ability of
      designed multiplex real-time PCR protocol for the rapid detection and
      quantification of six common microorganisms involved in endodontic infection
      before and after the PAD. MATERIALS AND METHODS: Samples were taken from the root
      canals of 50 patients with primary and secondary/persistent endodontic infections
      using sterile paper points. PAD with toluidine blue O (TBO) plus diode laser was
      performed on root canals. Resampling was then performed, and the samples were
      transferred to transport medium. Then, six target microorganisms were detected
      using multiplex real-time PCR before and after the PAD. RESULTS: Veillonella
      parvula was found using multiplex real-time PCR to have the highest frequency
      among samples collected before the PAD (29.4%), followed by Porphyromonas
      gingivalis (23.1%), Aggregatibacter actinomycetemcomitans (13.6%), Actinomyces
      naeslundii (13.0%), Enterococcus faecalis (11.5%), and Lactobacillus rhamnosus
      (9.4%). After TBO-mediated PAD, P. gingivalis strains, the most resistance
      microorganisms, were recovered in 41.7% of the samples using molecular approach
      (P > 0.05). CONCLUSION: As the results shown, multiplex real-time PCR as an
      accurate detection approach with high-throughput and TBO-mediated PAD as an
      efficient antimicrobial strategy due to the significant reduction of the
      endopathogenic count can be used for detection and treatment of microbiota
      involved in infected root canals, respectively.

PMID- 29337225
TI  - Bone, muscle, and metabolic parameters predict survival in patients with
      synchronous bone metastases from lung cancers.
AB  - BACKGROUND: Lung adenocarcinoma regularly induces bone metastases that are
      responsible for impaired quality of life as well as significant morbidity,
      including bone pain and fractures. We aimed at identifying whether bone and
      metabolic biomarkers were associated with the prognosis of lung adenocarcinoma
      patients with synchronous bone metastases. PATIENTS AND METHODS: POUMOS is a
      prospective cohort of patients diagnosed with lung adenocarcinoma and synchronous
      bone metastases. All patients underwent biopsy of bone metastases to confirm
      diagnosis, including genotyping of oncogenic drivers such as EGFR and KRAS. Whole
      body composition was assessed using DEXA scan. Serum levels of C-reactive
      protein, HbA1C, calcaemia, sCTX, and DKK1 were also measured. RESULTS: Sixty four
      patients, aged (mean +/- SD) 65 +/- 11 years, were included. Thirty-nine (61%)
      patients had a good performance status (PS 0-1); 56% had >5 bone lesions, and 41%
      a weight-bearing bone (femour or tibia) involvement. Median overall survival was
      7 months. In multivariate analysis, HbA1c (HR = 1.69 [1.10-2.63] per 0.5%
      decrease; p = .02), DKK1 (HR = 1.28 [1.01-1.61] per 10 ng/mL increase; p = .04),
      and hypercalcaemia (HR = 2.83 [1.10-7.30]; p = .03) were independently associated
      with poorer survival. In the subgroup of patients with DEXA, sarcopenia was also
      associated with poorer survival (HR = 2.96, 95%CI [1.40-6.27]; p = .005).
      CONCLUSIONS: In patients with lung adenocarcinoma and synchronous bone
      metastases, bone, sarcopenia, and metabolic parameters were predictors of poor
      overall survival independently of common prognostic factors. We suggest that, in
      addition to oncological therapy, supportive treatment dedicated to bone
      metastases, muscle wasting, and energy metabolism are essential to improve
      prognosis.

PMID- 29337226
TI  - GLP-1 signaling and alcohol-mediated behaviors; preclinical and clinical
      evidence.
AB  - Alcohol addiction, affecting approximately four percent of the population,
      contributes significantly to the global burden of diseases and is a substantial
      cost to the society. The neurochemical mechanisms regulating alcohol mediated
      behaviors is complex and in more recent years a new physiological role of the gut
      brain peptides, traditionally known to regulate appetite and food intake, have
      been suggested. Indeed, regulators of alcohol-mediated behaviors. One of these
      gut-brain peptides is the annorexigenic peptide glucagon-like peptide-1 (GLP-1),
      Preclinical studies show that GLP-1 receptor activation, either by GLP-1 or
      analogues, attenuate the ability of alcohol to activate the mesolimbic dopamine
      system as well as decrease alcohol consumption and operant self-administration.
      In further support for the endogenous GLP-1 system in addiction processes are the
      experimental data showing that a GLP-1 receptor antagonist increases alcohol
      intake. Moreover, GLP-1 receptor agonists prevent the ability of other addictive
      drugs to activate the mesolimbic dopamine system. The number of clinical studies
      is limited, but show i) that genetic variation in the GLP-1 receptor gene is
      associated with alcohol addiction as well as increased alcohol infusion in
      humans, ii) that plasma levels of GLP-1 are associated with the subjective
      experience of cocaine and iii) that a GLP-1 receptor agonist reduces alcohol
      intake in patients with type-2 diabetes mellitus. These experimental and clinical
      studies raises the concern that clinically available GLP-1 receptor agonists
      deserves to be tested as potential treatments of patients with addictive
      disorders including alcohol addiction. This article is part of the Special Issue
      entitled 'Metabolic Impairment as Risk Factors for Neurodegenerative Disorders.'

PMID- 29337228
TI  - WITHDRAWN: Monitoring the prevalence of genetically modified (GM) maize in Iran
      food products.
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- 29337227
TI  - Juvenile social defeat stress exposure persistently impairs social behaviors and
      neurogenesis.
AB  - Adverse juvenile experiences, including physical abuse, often have negative
      health consequences later in life. We investigated the influence of social defeat
      stress exposure as juveniles on neuropsychological behaviors, and the causal role
      of glucocorticoids in abnormal behaviors and impairment of neurogenesis in mice
      exposed to the stress. The juvenile (24-day-old) and adult (70-day-old) male
      C57BL/6J mice were exposed to social defeat stress induced by an aggressive ICR
      mouse. Social defeat stress exposure as juveniles, even for 1 day, induced
      persistent social avoidance to the unfamiliar ICR mouse in the social interaction
      test, but that was not observed in mice exposed to the stress as adults. Social
      avoidance by the stress exposure as juveniles for 10 consecutive days was
      observed, when the target mouse was not only unfamiliar ICR but also another
      C57BL/J mouse, but not an absent or an anesthetized ICR mouse. The stress
      exposure did not induce anxiety- and depression-like behaviors in spontaneous
      locomotor activity, elevated plus-maze test, marble-burying test, forced swimming
      test, or sucrose preference test. Serum corticosterone levels increased
      immediately after the stress exposure. The hippocampal neurogenesis was
      suppressed 1 day and 4 weeks after the stress exposure. Administration of
      mifepristone, a glucocorticoid receptor antagonist, prior to each stress
      exposure, blocked the persistent social avoidance and suppression of
      neurogenesis. In conclusion, social avoidance induced by social defeat stress
      exposure as juveniles are more persistent than that as adults. These social
      avoidances are associated with suppression of hippocampal neurogenesis via
      glucocorticoid receptors.

PMID- 29337229
TI  - Protective effect of flavonoids from Cyclocarya paliurus leaves against carbon
      tetrachloride-induced acute liver injury in mice.
AB  - Cyclocarya paliurus (Batal.) Iljinskaja (C. paliurus), known locally as 'sweet
      tea tree', is commonly cultivated in China. Flavonoids from Cyclocarya paliurus
      (Batal.) Iljinskaja (FC) is reported to exhibit multiple biological effects,
      including anti-inflammatory, anti-oxidant and anti-diabetic activities. However,
      their influence on carbon tetrachloride (CCl4)-induced acute liver injury remains
      unclear. This study was designed to investigate the hepatoprotective effect of
      total flavonoids from C. paliurus leaves. Results revealed that flavonoids from
      C. paliurus significantly decreased CCl4-induced elevation of activities of
      aspartate transaminase (AST), alanine transaminase (ALT) and superoxide dismutase
      (SOD) as well as the level of malondialdehyde (MDA), and markedly increased the
      levels of SOD, total antioxidant capacity (T-AOC) and glutathione peroxidase (GSH
      Px) compared with the model group. Structures of mainly compounds were elucidated
      by nuclear magnetic resonance (NMR), mass spectrometry (MS) spectroscopic and
      chemical analyses. This study clearly shows that flavonoids from C. paliurus
      exert a potent protective effect against CCl4-induced acute liver injury in mice.
      Its hepatoprotective effect appears to be closely associated with its antioxidant
      activity. The results indicated that flavonoids from C. paliurus leaves could be
      considered as a potent food supplement in the prevention of acute liver injury.

PMID- 29337230
TI  - Cholesterol modulates the liposome membrane fluidity and permeability for a
      hydrophilic molecule.
AB  - The effect of cholesterol (CHOL) content on the permeability and fluidity of
      dipalmitoylphosphatidylcholine (DPPC) liposome membrane was investigated.
      Liposomes encapsulating sulforhodamine B (SRB), a fluorescent dye, were prepared
      by reverse phase evaporation technique (REV) at various DPPC:CHOL molar ratios
      (from 100:0 to 100:100). The release kinetics of SRB was studied during 48 h in
      buffer (pH 7.4) containing NaCl at 37  degrees C. The DPPC:CHOL formulations were
      also characterized for their size, polydispersity index and morphology.
      Increasing CHOL concentration induced an increase in the mean liposomes size
      accompanying with a shape transition from irregular to nanosized, regular and
      spherical vesicles. The release kinetics of SRB showed a biphasic pattern; the
      release data was then analyzed using different mathematical models. On the
      overall, the SRB release was governed by a non-Fickian diffusion during the first
      period (0-10 h) while it followed a Fickian diffusion between 10 and 48 h.
      Changes in DPPC liposome membrane fluidity of various batches (CHOL% 0, 10, 20,
      30 and 100) were monitored by using 5- and 16 doxyl stearic acids (DSA) as spin
      labels. CHOL induced a decrease in the bilayer fluidity. Concisely, CHOL
      represents a critical component in modulating the release of hydrophilic
      molecules from lipid vesicles.

PMID- 29337232
TI  - DA Neurons Promote the Instigation and Maintenance of Effortful Responding: A
      Commentary on Fischbach-Weiss, Reese, and Janak.

PMID- 29337231
TI  - Apoptosis induction by Pleurotus sajor-caju (Fr.) Singer extracts on colorectal
      cancer cell lines.
AB  - Pleurotus sajor-caju (PSC) is an edible mushroom used in food supplements,
      presenting antitumor properties through induction of cell death pathways. The PSC
      potential against colorectal cancer was analyzed by exposing HCT116wt cells to
      different PSC extracts. The PSC n-hexane extract (PSC-hex) showed the highest
      cytotoxicity effect (IC50 value 0.05 mg/mL). The observed cytotoxicity was then
      associated to apoptosis-promoting and cell cycle-arrest pathways. PSC-hex was
      able to induce apoptosis related to breakdown of mitochondrial membrane potential
      and ROS generation. The absence of cytotoxicity in HTC116-p53 and HTC116-Bax
      cells, alongside with an increase in p53, Bax and Caspase-3 expression, and
      decrease in Bcl-2 expression, supports that the pro-apoptotic effect is probably
      induced through a p53 associated pathway. PSC-hex induced cell cycle arrest at
      G2/M in HCT116wt without cytotoxicity in HTC116-p21 cells. These findings suggest
      that a p21/p53 cell cycle regulation pathway is probably disrupted by compounds
      present on PSC-hex. Identification of the major components was then performed
      with ergosta-5,7,22-trien-3beta-ol representing 30.6% of total weight. In silico
      docking studies of ergosta-5,7,22-trien-3beta against Bcl-2 were performed and
      results show a credible interaction with the Bcl-2 hydrophobic cleft. The results
      show that PSC-hex can be used as supplementary food for adjuvant therapy in
      colorectal carcinoma.

PMID- 29337234
TI  - Electrophysiological Activity Prior to Self-initiated Movements is Related to
      Impulsive Personality Traits.
AB  - Electrophysiological and neuroimaging studies suggest that our actions are
      initiated by unconscious mental processes long before awareness of intention to
      act. The time window between the awareness of the intention to move and the
      movement onset, which normally permits to exert a conscious "veto" on the
      impending action, is modulated by individual differences in trait impulsivity. In
      particular, trait impulsive people show a delayed awareness of the intention to
      act, probably exceeding the "point of no return", after which the action can no
      longer be inhibited. In order to investigate if individual differences in the
      "veto" interval might be explained by differences in the readiness potential (RP)
      dynamics, nineteen healthy participants underwent an impulsivity trait assessment
      using the Barratt Impulsiveness Scale (BIS-11) and performed a task based on
      Libet's clock paradigm, during EEG recordings of pre-movement neural activity. We
      observed a positive relationship between impulsive personality trait and motor
      system excitability during the preparation of self-initiated movements. In
      particular, the RP showed an earlier negative rising phase and a greater
      amplitude, with the increasing of BIS-11 scores. Based on present results, we
      conclude hypothesizing that trait impulsivity might be characterized by less
      effective preparatory inhibition mechanisms, which have a fundamental role in the
      control of behavior.

PMID- 29337233
TI  - Tau Deficiency Down-Regulated Transcription Factor Orthodenticle Homeobox 2
      Expression in the Dopaminergic Neurons in Ventral Tegmental Area and Caused No
      Obvious Motor Deficits in Mice.
AB  - Tau protein participates in microtubule stabilization, axonal transport, and
      protein trafficking. Loss of normal tau function will exert a negative effect.
      However, current knowledge on the impact of tau deficiency on the motor behavior
      and related neurobiological changes is controversial. In this study, we examined
      motor functions and analyzed several proteins implicated in the maintenance of
      midbrain dopaminergic (DA) neurons (mDANs) function of adult and aged tau+/+,
      tau+/-, tau-/- mice. We found tau deficiency could not induce significant motor
      disorders. However, we discovered lower expression levels of transcription
      factors Orthodenticle homeobox 2 (OTX2) of mDANs in older aged mice. Compared
      with age-matched tau+/+ mice, there were 54.1% lower (p = 0.0192) OTX2 protein
      (OTX2-fluorescence intensity) in VTA DA neurons of tau+/- mice and 43.6% lower (p
      = 0.0249) OTX2 protein in VTA DA neurons of tau-/- mice at 18 months old.
      Combined with the relevant reports, our results suggested that tau deficiency
      alone might not be enough to mimic the pathology of Parkinson's disease. However,
      OTX2 down-regulation indicates that mDANs of tau-deficient mice will be more
      sensitive to toxic damage from MPTP.

PMID- 29337235
TI  - Frequency-specific Effective Connectivity in Subjects with Cerebral Infarction as
      Revealed by NIRS Method.
AB  - A connectivity-based approach can highlight the network reorganization in the
      chronic phases after stroke and contributes to the development of therapeutic
      interventions. Using dynamic Bayesian inference, this study aimed to assess the
      effective connectivity (EC) in various frequency bands through the near-infrared
      spectroscopy (NIRS) method in subjects with cerebral infarction (CI). A phase
      coupling model was established based on phase information extracted using the
      wavelet transform of NIRS signals. Coupling strength and the main coupling
      direction were estimated using dynamic Bayesian inference. Wilcoxon test and chi
      square test were used to determine the significant difference in EC between two
      groups. Results showed that the coupling strength of the EC in the CI group
      significantly decreased relative to that in the healthy group. The decrease was
      most significant in the frequency intervals IV (0.021 Hz-0.052 Hz; p = 0.0006)
      and VI (0.005 Hz-0.095 Hz; p = 0.0028). The main coupling direction changed from
      the right prefrontal cortex to the right motor cortex and left motor cortex in
      the frequency intervals IV (p1 = 0.041, p2 = 0.047) and II (p1 = 0.0017, p2 =
      0.0036), respectively. The EC decreased or was even lost significantly in the EC
      map of the CI group. Experimental results indicated that information propagation
      was blocked in the CI group than in the healthy group and resulted in the
      decreased coupling strength and connectivity loss. The main coupling direction of
      the motor section changed from driving into being driven because of the
      degradation of limb movement function.

PMID- 29337237
TI  - Uridine-5'-Triphosphate Partially Blocks Differentiation Signals and Favors a
      more Repair State in Cultured rat Schwann Cells.
AB  - Schwann cells (SCs) play a key role in peripheral nerve regeneration. After
      damage, they respond acquiring a repair phenotype that allows them to
      proliferate, migrate and redirect axonal growth. Previous studies have shown that
      Uridine-5'-Triphosphate (UTP) and its purinergic receptors participate in several
      pathophysiological responses in the nervous system. Our group has previously
      described how UTP induces the migration of a Schwannoma cell line and promotes
      wound healing. These data suggest that UTP participates in the signaling involved
      in the regeneration process. In the present study we evaluated UTP effects in
      isolated rat SCs and cocultures of SCs and dorsal root ganglia neurons. UTP
      reduced cAMP-dependent Krox-20 induction in SCs. UTP also reduced the N-cadherin
      re-expression that occurs when SCs and axons make contact. In myelinating
      cocultures, a non-significant tendency to a lower expression of P0 and MAG
      proteins in presence of UTP was observed. We also demonstrated that UTP induced
      SC migration without affecting cell proliferation. Interestingly, UTP was found
      to block neuregulin-induced phosphorylation of the ErbB3 receptor, a pathway
      involved in the regeneration process. These results indicate that UTP could acts
      as a brake to the differentiation signals, promoting a more migratory state in
      the repair-SCs.

PMID- 29337236
TI  - Maintenance of the Innate Seizure Threshold by Cyclooxygenase-2 is Not Influenced
      by the Translational Silencer, T-cell Intracellular Antigen-1.
AB  - Activity of neuronal cyclooxygenase-2 (COX-2), a primary source of PG synthesis
      in the normal brain, is enhanced by excitatory neurotransmission and this is
      thought to be involved in seizure suppression. Results herein showing that the
      incidence of pentylenetetrazole (PTZ)-induced convulsions is suppressed in
      transgenic mice overexpressing COX-2 in neurons support this notion. T-cell
      intracellular antigen-1 (TIA-1) is an mRNA binding protein that is known to bind
      to COX-2 mRNA and repress its translation in non-neuronal cell types. An
      examination of the expression profile of TIA-1 protein in the normal brain
      indicated that it is expressed broadly by neurons, including those that express
      COX-2. However, whether TIA-1 regulates COX-2 protein levels in neurons is not
      known. The purpose of this study was to test the possibility that deletion of TIA
      1 increases basal COX-2 expression in neurons and consequently raises the seizure
      threshold. Results demonstrate that neither the basal nor seizure-induced
      expression profiles of COX-2 were altered in mice lacking a functional TIA-1 gene
      suggesting that TIA-1 does not contribute to regulation of COX-2 protein
      expression in neurons. The acute PTZ-induced seizure threshold was also unchanged
      in mice lacking TIA-1 protein, indicating that this RNA binding protein does not
      influence the innate seizure threshold. Nevertheless, the results raise the
      possibility that the level of neuronal COX-2 expression may be a determinant of
      the innate seizure threshold and suggest that a better understanding of the
      regulation of COX-2 expression in the brain could provide new insight into the
      molecular mechanisms that suppress seizure induction.

PMID- 29337238
TI  - Advantages of the Alpha-lipoic Acid Association with Chlorpromazine in a Model of
      Schizophrenia Induced by Ketamine in Rats: Behavioral and Oxidative Stress
      evidences.
AB  - Schizophrenia is a chronic mental disorder reported to compromise about 1% of the
      world's population. Although its pathophysiological process is not completely
      elucidated, evidence showing the presence of an oxidative imbalance has been
      increasingly highlighted in the literature. Thus, the use of antioxidant
      substances may be of importance for schizophrenia treatment. The objective of
      this study was to evaluate the behavioral and oxidative alterations by the
      combination of chlorpromazine (CP) and alpha-lipoic acid (ALA), a potent
      antioxidant, in the ketamine (KET) model of schizophrenia in rats. Male Wistar
      rats (200-300 g) were treated for 10 days with saline, CP or ALA alone or in
      combination with CP previous to KET and the behavioral (open field, Y-maze and
      PPI tests) and oxidative tests were performed on the last day of treatment. The
      results showed that KET induced hyperlocomotion, impaired working memory and
      decreased PPI. CP alone or in combination with ALA prevented KET-induced
      behavioral effects. In addition, the administration of KET decreased GSH and
      increased nitrite, lipid peroxidation and myeloperoxidase activity. CP alone or
      combined with ALA prevented the oxidative alterations induced by KET. In
      conclusion, the treatment with KET in rats induced behavioral impairments
      accompanied by hippocampal oxidative alterations, possibly related to NMDA
      receptors hypofunction. Besides that, CP alone or combined with ALA prevented
      these effects, showing a beneficial activity as antipsychotic agents.

PMID- 29337239
TI  - Background Suppression and its Relation to Foreground Processing of Speech Versus
      Non-speech Streams.
AB  - Since sound perception takes place against a background with a certain amount of
      noise, both speech and non-speech processing involve extraction of target signals
      and suppression of background noise. Previous works on early processing of speech
      phonemes largely neglected how background noise is encoded and suppressed. This
      study aimed to fill in this gap. We adopted an oddball paradigm where speech
      (vowels) or non-speech stimuli (complex tones) were presented with or without a
      background of amplitude-modulated noise and analyzed cortical responses related
      to foreground stimulus processing, including mismatch negativity (MMN), N2b, and
      P300, as well as neural representations of the background noise, that is,
      auditory steady-state response (ASSR). We found that speech deviants elicited
      later and weaker MMN, later N2b, and later P300 than non-speech ones, but N2b and
      P300 had similar strength, suggesting more complex processing of certain acoustic
      features in speech. Only for vowels, background noise enhanced N2b strength
      relative to silence, suggesting an attention-related speech-specific process to
      improve perception of foreground targets. In addition, noise suppression in
      speech contexts, quantified by ASSR amplitude reduction after stimulus onset, was
      lateralized towards the left hemisphere. The left-lateralized suppression
      following N2b was associated with the N2b enhancement in noise for speech,
      indicating that foreground processing may interact with background suppression,
      particularly during speech processing. Together, our findings indicate that the
      differences between perception of speech and non-speech sounds involve not only
      the processing of target information in the foreground but also the suppression
      of irrelevant aspects in the background.

PMID- 29337240
TI  - Prevention of the Severity of Post-ischemic Inflammation and Brain Damage by
      Simultaneous Knockdown of Toll-like Receptors 2 and 4.
AB  - Toll-like receptor 2 (TLR2) and TLR4 belong to a family of highly conserved
      pattern recognition receptors and are well-known upstream sensors of signaling
      pathways of innate immunity. TLR2 and TLR4 upregulation is thought to be
      associated with poor outcome in stroke patients. We currently show that transient
      focal ischemia in adult rats induces TLR2 and TLR4 expression within hours and
      shRNA-mediated knockdown of TLR2 and TLR4 alone and in combination decreases the
      infarct size and swelling. We further show that TLR2 and TLR4 knockdown also
      prevented the induction of their downstream signaling molecules MyD88, IRAK1, and
      NFkappaB p65 as well as the pro-inflammatory cytokines IL-1beta, IL-6, and
      TNFalpha. This study thus shows that attenuation of the severity of TLR2- and
      TLR4-mediated post-stroke inflammation ameliorates ischemic brain damage.

PMID- 29337241
TI  - Differential Effects of Alzheimer's Disease Abeta40 and 42 on Endocytosis and
      Intraneuronal Trafficking.
AB  - Anomalous neuronal accumulation of Abeta peptides was shown to affect synaptic
      transmission and contribute to neurodegeneration in Alzheimer's disease (AD)
      brain. Neuronal cells internalize amyloid beta (Abeta) peptides from the brain
      extracellular space even under normal physiological conditions, and these
      endocytotic pathways go awry during AD progression. We hypothesized that exposure
      to toxic Abeta species accumulating in AD brain contributes to perturbations in
      neuronal endocytosis. We have shown substantial down-regulation of KEGG
      endocytotic pathway genes in AD patient brain regions that accumulate Abeta
      compared to those in non-demented individuals. While both Abeta40 and Abeta42
      perturbed endocytosis and intracellular trafficking in neuronal cells, Abeta40
      had a greater effect than Abeta42. Moreover, Abeta40 decreased the neuronal
      uptake and lysosomal accumulation of Abeta42, which tends to oligomerize at low
      lysosomal pH. Hence, Abeta40 may reduce the prevalence of stable Abeta42
      oligomers that are closely associated with neurodegeneration and are
      intercellularly propagated across the vulnerable brain regions to eventually
      nucleate as amyloid plaques. In conclusion, elevated brain Abeta levels and
      Abeta42:40 ratio apparent in the early stages of AD could perturb intraneuronal
      trafficking, augment the anomalous accumulation of amyloid peptides in AD brain,
      and drive AD pathogenesis.

PMID- 29337242
TI  - Expression of GAEC1 mRNA and protein and its association with clinical and
      pathological parameters of patients with colorectal adenocarcinoma.
AB  - AIM: GAEC1 (Gene amplified in esophageal cancer 1) is an oncogene with key
      regulatory roles in the pathogenesis of oesophageal and colorectal carcinomas.
      The aim of this study was to investigate expression profiles and
      clinicopathological significance of GAEC1 mRNA and protein in patients with
      colorectal carcinomas. METHOD: Matched cancer and non-cancer fresh frozen tissues
      were prospectively collected from 80 patients diagnosed with colorectal
      adenocarcinoma (39 men and 41 women). The tissues were sectioned for RNA
      extraction and cDNA conversion and quantified by a real-time polymerase chain
      reaction. GAEC1 protein expression was analysed by immunohistochemistry using a
      custom made GAEC1 antibody. RESULT: GAEC1 mRNA was upregulated in majority (52%,
      n=42/80) of the colorectal carcinomas when compared to the matched non-neoplastic
      tissues. High expression of GAEC1 mRNA as correlated with patients of younger age
      (p=0.008), with lower grade carcinoma (p=0.028), presence of synchronous
      adenocarcinomas (p=0.034) and without any associated adenomas (p=0.047). In
      addition, patients with high GAEC1 mRNA overexpression had a shorter survival
      time. Furthermore, high GAEC1 protein expression was noted among patients having
      perforated colorectal carcinoma (p=0.04). CONCLUSION: The high expression of
      GAEC1 mRNA/protein as well as its correlation with multiple clinicopathological
      characteristics in patients with colorectal carcinoma strongly suggests that
      GAEC1 is a key regulator in the initiation of colorectal carcinogenesis.

PMID- 29337243
TI  - Intratumoral morphological heterogeneity can be an indicator of genetic
      heterogeneity in colorectal cancer.
AB  - Anti-EGFR-targeted therapy is used to treat metastatic colorectal cancers with
      RAS wild-type. However, resistance to targeted therapy is often observed and can
      be primary or acquired. One reason for primary resistance is the presence of
      mutations that are undetected due to genetic heterogeneity, which can be
      expressed by differences present in primary tumor and distant metastasis or
      recurrence or by an intratumoral heterogeneity (presence of different subclones
      in the investigated tumor sample). The aim of our study was to investigate if
      morphological heterogeneity can be an indicator of intratumoral heterogeneity. We
      analysed 13 samples with homogeneous and six samples with heterogeneous
      morphology with NGS. We were able to demonstrate that intratumoral genetic
      heterogeneity is present in all studied tumor samples, independent of homogeneous
      or heterogeneous morphology. Moreover, one sample of our cohort with
      morphological and genetic heterogeneity had a genetic wild-type profile in one
      tumor component. Therefore, we recommend to include each morphologically
      identifiable tumor component in the mutational analysis to not overlook
      resistance-inducing or potentially targetable mutations.

PMID- 29337244
TI  - MiR-142-5p act as an oncogenic microRNA in colorectal cancer: Clinicopathological
      and functional insights.
AB  - OBJECTIVES: miR-142-5p was noted aberrantly expressed and plays important roles
      in different pathophysiological conditions in human. The present study aims to
      examine the expression of miR-142-5p and its association with clinicopathological
      factors in a large cohort of patients with colorectal cancer. In addition, the
      cellular effects of miR-142-5p and its interacting targets in colon cancer cells
      were investigated. METHODS: Expression of miR-142-5p in colorectal cancer tissues
      (n=125) and colon cancer cell lines were analysed using real-time polymerase
      chain reaction. In vitro assays (cell proliferation, wound healing and colony
      formation) were used to study the miR-142-5p induced cellular effects. Western
      blots were used to examine the modulation of FAM134B, KRAS, EPAS1 and KLF6
      proteins expression followed by miR-142-5p expression-manipulation. RESULTS:
      Significant high expression of miR-142-5p was noted in cancer tissues and cells
      when compared to the controls (p<0.001). Overexpression of miR-142-5p in patients
      with colorectal cancer was common (72%; 90/125). miR-142-5p overexpression was
      associated with cancer in the proximal colorectum and with B-raf positive
      patients (p=0.05). Exogenous overexpression of miR-142-5p resulted in
      significantly increased cell proliferation, colony formation, and wound healing
      capacities, whereas inhibition of endogenous miR-142-5p led reduced cancer growth
      properties. The cellular effects of miR-142-5p were mediated by the modulation of
      tumour suppressor KLF6 expression, as the expression of miR-142-5p and KLF6
      protein are inversely correlated in colon cancer cells. CONCLUSION: High miR-142
      5p expression was associated with the biological aggressiveness of cancer. Thus,
      suppression of miR-142-5p could be a therapeutic strategy for patients with
      colorectal cancers.

PMID- 29337246
TI  - TLR3 gene in Japanese sea perch (Lateolabrax japonicus): Molecular cloning,
      characterization and expression analysis after bacterial infection.
AB  - Toll-like receptors (TLRs) play important roles in fish innate immune and are
      involved in the defense process of bacteria invasion. In the present study, the
      full-length cDNA of TLR3 from the sea perch, Lateolabrax japonicus, was cloned
      and characterized. The full length of LjTLR3 cDNA was 3265 bp including an open
      reading frame of 2679 bp encoding a peptide of 922 amino acids. Tissues
      distribution analysis indicated that LjTLR3 showed a tissue-specific variation
      with high expression in spleen, head-kidney and liver. In order to investigate
      LjTLR3 functions against bacteria infection, the expression patterns of LjTLR3
      after Vibrio harveyi and Streptococcus agalactiae challenge were detected by qRT
      PCR, and the results showed that LjTLR3 was significant up-regulated after both
      bacteria stimulation in head-kidney, spleen and liver in a time-depended manner.
      Furthermore, the results by in situ hybridization experiments showed that
      positive signals of LjTLR3 mRNA in infected spleen and head-kidney were more
      numerous than that in the control group. In addition, intracellular localization
      revealed that LjTLR3 is distributed in the cytoplasm. In summary, these findings
      suggest that LjTLR3 was involved in the immune process under bacteria infection.
      This study would benefit to further clarify the roles of fish TLRs in the immune
      process and contribute to further study on enhancing disease resistance of L.
      japonicus.

PMID- 29337245
TI  - Hepatic alcohol dehydrogenase deficiency induces pancreatic injury in chronic
      ethanol feeding model of deer mice.
AB  - The single most common cause of chronic pancreatitis (CP, a serious inflammatory
      disease) is chronic alcohol abuse, which impairs hepatic alcohol dehydrogenase
      (ADH, a major ethanol oxidizing enzyme). Previously, we found ~5 fold greater
      fatty acid ethyl esters (FAEEs), and injury in the pancreas of hepatic ADH
      deficient (ADH-) vs. hepatic normal ADH (ADH+) deer mice fed 3.5g% ethanol via
      liquid diet daily for two months. Therefore, progression of ethanol-induced
      pancreatic injury was determined in ADH- deer mice fed ethanol for four months to
      delineate the mechanism and metabolic basis of alcoholic chronic pancreatitis
      (ACP). In addition to a substantially increased blood alcohol concentration and
      plasma FAEEs, significant degenerative changes, including atrophy and loss of
      acinar cells in some areas, ultrastructural changes evident by such features as
      swelling and disintegration of endoplasmic reticulum (ER) cisternae and ER stress
      were observed in the pancreas of ethanol-fed ADH- deer mice vs. ADH+ deer mice.
      These changes are consistent with noted increases in pancreatic injury markers
      (plasma lipase, pancreatic trypsinogen activation peptide, FAEE synthase and
      cathepsin B) in ethanol-fed ADH- deer mice. Most importantly, an increased levels
      of pancreatic glucose regulated protein (GRP) 78 (a prominent ER stress marker)
      were found to be closely associated with increased phosphorylated eukaryotic
      initiation factor (eIF) 2alpha signaling molecule in PKR-like ER kinase branch of
      unfolded protein response (UPR) as compared to X box binding protein 1S and
      activating transcription factor (ATF)6 - 50kDa protein of inositol requiring
      enzyme 1alpha and ATF6 branches of UPR, respectively, in ethanol-fed ADH- vs.
      ADH+ deer mice. These results along with findings on plasma FAEEs, and pancreatic
      histology and injury markers suggest a metabolic basis of ethanol-induced
      pancreatic injury, and provide new avenues to understand metabolic basis and
      molecular mechanism of ACP.

PMID- 29337247
TI  - Effects of dietary administration of fenugreek seeds on metabolic parameters and
      immune status of gilthead seabream (Sparus aurata L.).
AB  - Medical plants could be used as a prophylactic method in aquaculture because they
      are considered safe and so very promising alternatives to the use of chemicals.
      The aim of the present work was to examine the effects of dietary fenugreek
      (Trigonella foenum graecum) seeds administered for 8 weeks on the metabolic and
      immune status of gilthead seabream (Sparus aurata L.). Four experimental groups
      were designated: one receiving a basal diet (control) and three fed powdered
      fenugreek seeds incorporated in the fish feed at 1%, 5% and 10%. The results show
      that significant decreases in aspartate aminotransferase, creatine kinase,
      potassium and the albumin/globulin ratio were detected in the serum of fish fed
      10% fenugreek compared with the values recorded in control fish. As regards the
      immune status, fish fed the 5% supplemented diet had higher haemolytic complement
      and peroxidase activities than the control fish whilst antiprotease activity was
      higher in fish fed the 1% fenugreek level respect to control fish and the fish
      fed the highest fenugreek supplementation rate. Interestingly, the results also
      revealed a significant enhancement of most of the cellular immune parameters
      studied, especially in fish fed the highest level of fenugreek (10%). However,
      the bacteriostatic activity of serum against fish pathogenic and non-pathogenic
      bacteria was non-affected to any significant extent in fish fed the supplemented
      diets. Overall, the results suggest that the high level of dietary fenugreek
      tested in this work (10%) did not negatively affect any of the metabolic
      parameters measured in serum but increased some of them. In addition, the
      inclusion of fenugreek seeds in the gilthead seabream diet at 5% or 10% improved
      the humoral and cellular immune activities, respectively. Further studies are
      needed to better understand the effects of this natural product, which may be
      suitable for use as a feed additive in fish aquaculture.

PMID- 29337248
TI  - Immunohistochemical characterization of epidermal dendritic-like cells in giant
      mudskipper, Periophthalmodon schlosseri.
AB  - Giant Mudskipper, Periophthalmodon schlosseri (Pallas, 1770), is euryhaline,
      amphibious, and air-breathing fish. These fishes live in close association to
      mangrove forests and often spend over 90% of time out of water, in adjacent
      mudflats. They have developed morphological and physiological adaptations to
      satisfy their unique lifestyles. The skin is the primary interface between the
      body and the environment, and has a central role in host defence. The initiation
      of immune responses to antigens in the vertebrate skin has often been attributed
      to epidermal Langerhans'cells (LC) that are dendritic cells (DC), antigen
      presenting cells (APC) which reside in the epidermis. Dendritic cells have been
      characterized morphologically and functionally in the teleost fish tissues such
      as rainbow trout, salmonids, medaka, African catfish and zebrafish. However,
      there is no evidence of the presence of DCs and their role in mudskippers
      immunity. The aim of this preliminary study was to characterize, through use of
      specific antibodies: Toll-like receptor 2, S100, serotonin (5-HT), and Vesicular
      acetylcholine transporter VAChT, a specific DC-like subpopulation in Pn.
      schlosseri's epidermis.

PMID- 29337249
TI  - Regulation of lactate dehydrogenase in response to WSSV infection in the shrimp
      Litopenaeus vannamei.
AB  - Lactate dehydrogenase (LDH) is key for anaerobic glycolysis. LDH is induced by
      the hypoxia inducible factor -1 (HIF-1). HIF-1 induces genes involved in glucose
      metabolism and regulates cellular oxygen homeostasis. HIF-1 is formed by a
      regulatory alpha-subunit (HIF-1alpha) and a constitutive beta-subunit (HIF
      1beta). The white spot syndrome virus (WSSV) induces anaerobic glycolysis in
      shrimp hemocytes, associated with lactate accumulation. Although infection and
      lactate production are associated, the LDH role in WSSV-infected shrimp has not
      been examined. In this work, the effects of HIF-1 silencing on the expression of
      two LDH subunits (LDHvan-1 and LDHvan-2) in shrimp infected with the WSSV were
      studied. HIF-1alpha transcripts increased in gills, hepatopancreas, and muscle
      after WSSV infection, while HIF-1beta remained constitutively expressed. The
      expression for both LDH subunits increased in each tissue evaluated during the
      WSSV infection, translating into increased enzyme activity. Glucose concentration
      increased in each tissue evaluated, while lactate increased in gills and
      hepatopancreas, but not in muscle. Silencing of HIF-1alpha blocked the increase
      of LDH expression and enzyme activity, along with glucose (all tissues) and
      lactate (gills and hepatopancreas) concentrations produced by WSSV infection.
      These results demonstrate that HIF-1 up regulates the expression of LDH subunits
      during WSSV infection, and that this induction contributes to substrate
      metabolism in energetically active tissues of infected shrimp.

PMID- 29337250
TI  - The STIM1 inhibitor ML9 disrupts basal autophagy in cardiomyocytes by decreasing
      lysosome content.
AB  - Stromal-interaction molecule 1 (STIM1)-mediated store-operated Ca2+ entry (SOCE)
      plays a key role in mediating cardiomyocyte hypertrophy, both in vitro and in
      vivo. Moreover, there is growing support for the contribution of SOCE to the Ca2+
      overload associated with ischemia/reperfusion injury. Therefore, STIM1 inhibition
      is proposed as a novel target for controlling both hypertrophy and
      ischemia/reperfusion-induced Ca2+ overload. Our aim was to evaluate the effect of
      ML9, a STIM1 inhibitor, on cardiomyocyte viability. ML9 was found to induce cell
      death in cultured neonatal rat cardiomyocytes. Caspase-3 activation, apoptotic
      index and release of the necrosis marker lactate dehydrogenase to the
      extracellular medium were evaluated. ML9-induced cardiomyocyte death was not
      associated with increased intracellular ROS or decreased ATP levels. Moreover,
      treatment with ML9 significantly increased levels of the autophagy marker LC3-II,
      without altering Beclin1 or p62 protein levels. However, treatment with ML9
      followed by bafilomycin-A1 did not produce further increases in LC3-II content.
      Furthermore, treatment with ML9 resulted in decreased LysoTracker(r) Green
      staining. Collectively, these data suggest that ML9-induced cardiomyocyte death
      is triggered by a ML9-dependent disruption of autophagic flux due to lysosomal
      dysfunction.

PMID- 29337251
TI  - Chromatin organization regulated by EZH2-mediated H3K27me3 is required for OPN
      induced migration of bone marrow-derived mesenchymal stem cells.
AB  - Osteopontin (OPN) is a chemokine-like extracellular matrix-associated protein
      involved in the migration of bone marrow-derived mesenchymal stem cells (BMSCs).
      An increasing number of studies have found that chromatin organization may affect
      cellular migration. However, whether OPN regulates chromatin organization is not
      understood, nor are the underlying molecular mechanisms. In this study, we
      investigated the link between chromatin organization and BMSC migration and
      demonstrated that OPN-mediated BMSC migration leads to elevated levels of
      heterochromatin marker histone H3 lysine 27 trimethylation (H3K27me3) through the
      methyltransferase EZH2. The expression of EZH2 reorganizes the chromatin
      structure of BMSCs. Pharmacological inhibition or depletion of EZH2 blocks BMSC
      migration. Moreover, using an atomic force microscope (AFM), we found that
      chromatin decondensation alters the mechanical properties of the nucleus. In
      addition, inhibition of extracellular signal-regulated kinase 1/2 (ERK1/2)
      signals represses OPN-promoted chromatin condensation and cell migration. Thus,
      our results identify a mechanism by which ERK1/2 signalling drives specific
      chromatin modifications in BMSCs, which alters chromatin organization and thereby
      enables OPN-mediated BMSC migration.

PMID- 29337252
TI  - Phosphatases catching up with the level of knowledge: Finally druggable?

PMID- 29337253
TI  - Should standardized susceptibility testing for microbial biofilms be introduced
      in clinical practice?

PMID- 29337254
TI  - Are we living in an antibiotic resistance nightmare?

PMID- 29337255
TI  - A comparative study of American and Chinese college students' motives for food
      choice.
AB  - Previous cross-cultural research has examined college students' food choice
      decisions in different countries. The current study aimed to add to the
      literature by examining similarities and differences in motives for food choice
      between American (N = 328) and Chinese (N = 333) college students. The Food
      Choice Questionnaire (FCQ) was used to measure the participants' motives for food
      choice. Students' perceptions on the importance of diet and on their body
      satisfaction were also obtained. Results show that, while there are many
      similarities between the two cultural groups on the FCQ items, there are also
      significant differences. Specifically, the two groups view sensory appeal,
      weight, health, mood, and familiarity in a similar way, but the American
      participants score higher on price and convenience whereas the Chinese score
      higher on natural content and ethical concerns. We believe contextual cultural
      factors of each country may be related to these results. Women view sensory
      appeal and weight as significantly more important than men. Interactions between
      culture and gender are also found. For example, American women score
      significantly higher than American men on mood whereas there is no gender
      difference in the Chinese group; on the other hand, Chinese men score
      significantly higher on price than Chinese women whereas there is no gender
      difference in the American group.

PMID- 29337256
TI  - MicroRNA regulatory networks reflective of polyhexamethylene guanidine phosphate
      induced fibrosis in A549 human alveolar adenocarcinoma cells.
AB  - Polyhexamethylene guanidine phosphate (PHMG-phosphate), an active component of
      humidifier disinfectant, is suspected to be a major cause of pulmonary fibrosis.
      Fibrosis, induced by recurrent epithelial damage, is significantly affected by
      epigenetic regulation, including microRNAs (miRNAs). The aim of this study was to
      investigate the fibrogenic mechanisms of PHMG-phosphate through the profiling of
      miRNAs and their target genes. A549 cells were treated with 0.75 MUg/mL PHMG
      phosphate for 24 and 48 h and miRNA microarray expression analysis was conducted.
      The putative mRNA targets of the miRNAs were identified and subjected to Gene
      Ontology analysis. After exposure to PHMG-phosphate for 24 and 48 h, 46 and 33
      miRNAs, respectively, showed a significant change in expression over 1.5-fold
      compared with the control. The integrated analysis of miRNA and mRNA microarray
      results revealed the putative targets that were prominently enriched were
      associated with the epithelial-mesenchymal transition (EMT), cell cycle changes,
      and apoptosis. The dose-dependent induction of EMT by PHMG-phosphate exposure was
      confirmed by western blot. We identified 13 putative EMT-related targets that may
      play a role in PHMG-phosphate-induced fibrosis according to the Comparative
      Toxicogenomic Database. Our findings contribute to the comprehension of the
      fibrogenic mechanism of PHMG-phosphate and will aid further study on PHMG
      phosphate-induced toxicity.

PMID- 29337258
TI  - Adding injury to infection: The relationship between injury status and genetic
      diversity of Theileria infecting plains zebra, Equus quagga.
AB  - Asymptomatic tick-borne infections are a common feature in wild herbivores. In
      human-dominated habitats, snare injuries to wild herbivores are common and are
      likely to co-occur with enzootic infections. The influence of injury on pattern,
      course and outcome of enzootic infection in wild herbivores is unknown. We
      identified Theileria species infecting zebra and assessed the relationship
      between host injury-status and parasitaemia, parasite diversity and selection
      regimes. We also determined host leucocyte differential as this can reveal
      mechanisms by which injuries influence infections. Theileria infecting zebra was
      identified using PCR and sequencing of the V4 region of the 18 s rRNA gene and
      confirmed with phylogenetic analyses. The influence of injury status on parasite
      infection patterns, genetic diversity and selection were assessed using
      population genetic tools. Parasitaemia estimated from prevalence and leucocyte
      differential were determined from microscopic examination of Giemsa stained thin
      blood smears. Phylogenetic and sequence analyses revealed that the zebra
      population studied was infected with three Theileria equi haplotypes.
      Parasitaemia was lower among injured compared to non-injured animals and lower
      during dry than wet season. Mean (+/-SD) genetic diversity was 0.386 (+/-0.128)
      in injured and 0.513 (+/-0.144) in non-injured zebra (P = .549). Neutrality tests
      indicated that T. equi is under strong purifying selection in injured females (Li
      & Fu's D* = -2.037) and demographic expansion in all zebra during the wet season
      (Tajima D = -1.904). Injured zebras had a higher median per cent of neutrophils
      (64% vs 37%) a lower median per cent of basophils (0% vs 1%) and eosinophils (2%
      vs 4.5%) than non-injured animals, suggesting a heightened immune response and a
      shift from a Th2 to Th1 T-Cell response favoring the elimination of intracellular
      parasites in injured animals. This study demonstrates the utility of population
      genetics in revealing factors influencing parasite diversity and infection
      patterns.

PMID- 29337257
TI  - A comparison of the embryonic stem cell test and whole embryo culture assay
      combined with the BeWo placental passage model for predicting the embryotoxicity
      of azoles.
AB  - In the present study, we show the value of combining toxico-dynamic and -kinetic
      in vitro approaches for embryotoxicity testing of azoles. Both the whole embryo
      culture (WEC) and the embryonic stem cells test (EST) predicted the in vivo
      potency ranking of twelve tested azoles with moderate accuracy. Combining these
      results with relative placental transfer rates (Papp values) as determined in the
      BeWo cell culture model, increased the predictability of both WEC and EST, with
      R2 values increasing from 0.51 to 0.87 and from 0.35 to 0.60, respectively. The
      comparison of these in vitro systems correlated well (R2 = 0.67), correctly
      identifying the in vivo strong and weak embryotoxicants. Evaluating also specific
      gene responses related with the retinoic acid and sterol biosynthesis pathways,
      which represent the toxicological and fungicidal mode of action of azoles
      respectively in the WEC and EST, we observed that the differential regulation of
      Dhrs3 and Msmo1 reached higher magnitudes in both systems compared to Cyp26a1 and
      Cyp51. Establishing sensitive biomarkers across the in vitro systems for studying
      the underlying mechanism of action of chemicals, such as azoles, is valuable for
      comparing alternative in vitro models and for improving insight in the mechanism
      of developmental toxicity of chemicals.

PMID- 29337259
TI  - Mathematical modeling of tumor-induced immunosuppression by myeloid-derived
      suppressor cells: Implications for therapeutic targeting strategies.
AB  - Myeloid-derived suppressor cells (MDSCs) belong to immature myeloid cells that
      are generated and accumulated during the tumor development. MDSCs strongly
      suppress the anti-tumor immunity and provide conditions for tumor progression and
      metastasis. In this study, we present a mathematical model based on ordinary
      differential equations (ODE) to describe tumor-induced immunosuppression caused
      by MDSCs. The model consists of four equations and incorporates tumor cells,
      cytotoxic T cells (CTLs), natural killer (NK) cells and MDSCs. We also provide
      simulation models that evaluate or predict the effects of anti-MDSC drugs (e.g.,
      l-arginine and 5-Fluorouracil (5-FU)) on the tumor growth and the restoration of
      anti-tumor immunity. The simulated results obtained using our model were in good
      agreement with the corresponding experimental findings on the expansion of
      splenic MDSCs, immunosuppressive effects of these cells at the tumor site and
      effectiveness of l-arginine and 5-FU on the re-establishment of antitumor
      immunity. Regarding this latter issue, our predictive simulation results
      demonstrated that intermittent therapy with low-dose 5-FU alone could eradicate
      the tumors irrespective of their origins and types. Furthermore, at the time of
      tumor eradication, the number of CTLs prevailed over that of cancer cells and the
      number of splenic MDSCs returned to the normal levels. Finally, our predictive
      simulation results also showed that the addition of l-arginine supplementation to
      the intermittent 5-FU therapy reduced the time of the tumor eradication and the
      number of iterations for 5-FU treatment. Thus, the present mathematical model
      provides important implications for designing new therapeutic strategies that aim
      to restore antitumor immunity by targeting MDSCs.

PMID- 29337261
TI  - Heart rate variability alters cardiac repolarization and electromechanical
      dynamics.
AB  - Heart rate continuously varies due to autonomic regulation, stochasticity in
      pacemaking, and circadian rhythm, collectively termed heart rate variability
      (HRV), during normal physiological conditions. Low HRV is clinically associated
      with an elevated risk of cardiac arrhythmias. Alternans, a beat-to-beat
      alternation in action potential duration (APD) and/or intracellular calcium (Ca)
      transient, is a well-known risk factor associated with cardiac arrhythmias that
      is typically studied under conditions of a constant pacing rate, i.e., the
      absence of HRV. In this study, we investigate the effects of HRV on the interplay
      between APD, Ca, and electromechanical properties, employing a nonlinear discrete
      time map model that governs APD and intracellular Ca cycling with a stochastic
      pacing period. We find that HRV can decrease variation in APD and peak Ca at fast
      pacing rates for which alternans is present. Further, increased HRV typically
      disrupts the alternating pattern for both APD and peak Ca and weakens the
      correlation between APD and peak Ca, thus decoupling Ca-mediated instabilities
      from repolarization alternation. We find that the efficacy of these effects is
      regulated by the sarcoplasmic reticulum Ca uptake rate. Overall, these results
      demonstrate that HRV disrupts arrhythmogenic alternans and suggests that HRV may
      be a significant factor in preventing life-threatening arrhythmias.

PMID- 29337260
TI  - Modelling and simulation of biased agonism dynamics at a G protein-coupled
      receptor.
AB  - Theoretical models of G protein-coupled receptor (GPCR) concentration-response
      relationships often assume an agonist producing a single functional response via
      a single active state of the receptor. These models have largely been analysed
      assuming steady-state conditions. There is now much experimental evidence to
      suggest that many GPCRs can exist in multiple receptor conformations and elicit
      numerous functional responses, with ligands having the potential to activate
      different signalling pathways to varying extents-a concept referred to as biased
      agonism, functional selectivity or pluri-dimensional efficacy. Moreover, recent
      experimental results indicate a clear possibility for time-dependent bias,
      whereby an agonist's bias with respect to different pathways may vary
      dynamically. Efforts towards understanding the implications of temporal bias by
      characterising and quantifying ligand effects on multiple pathways will clearly
      be aided by extending current equilibrium binding and biased activation models to
      include G protein activation dynamics. Here, we present a new model of time
      dependent biased agonism, based on ordinary differential equations for multiple
      cubic ternary complex activation models with G protein cycle dynamics. This model
      allows simulation and analysis of multi-pathway activation bias dynamics at a
      single receptor for the first time, at the level of active G protein (alphaGTP),
      towards the analysis of dynamic functional responses. The model is generally
      applicable to systems with NG G proteins and N* active receptor states. Numerical
      simulations for NG=N*=2 reveal new insights into the effects of system parameters
      (including cooperativities, and ligand and receptor concentrations) on bias
      dynamics, highlighting new phenomena including the dynamic inter-conversion of
      bias direction. Further, we fit this model to 'wet' experimental data for two
      competing G proteins (Gi and Gs) that become activated upon stimulation of the
      adenosine A1 receptor with adenosine derivative compounds. Finally, we show that
      our model can qualitatively describe the temporal dynamics of this competing G
      protein activation.

PMID- 29337262
TI  - Longitudinal patterns and response lengths of algae in riverine ecosystems: A
      model analysis emphasising benthic-pelagic interactions.
AB  - In riverine ecosystems primary production is principally possible in two
      habitats: in the benthic layer by sessile algae and in the surface water by
      planktonic algae being transported downstream. The relevance of these two
      habitats generally changes along the rivers' continuum. However, analyses of the
      interaction of algae in these two habitats and their controlling factors in
      riverine ecosystems are, so far, very rare. We use a simplified advection
      diffusion model system combined with ecological process kinetics to analyse the
      interaction of benthic and planktonic algae and nutrients along idealised streams
      and rivers at regional to large scales. Because many of the underlying processes
      affecting algal dynamics are influenced by depth, we focus particularly on the
      impact of river depth on this interaction. At constant environmental conditions
      all state variables approach stable spatial equilibria along the river,
      independent of the boundary conditions at the upstream end. Because our model is
      very robust against changes of turbulent diffusion and stream velocity, these
      spatial equilibria can be analysed by a simplified ordinary differential equation
      (ode) version of our model. This model variant reveals that at shallower river
      depths, phytoplankton can exist only when it is subsidised by detaching benthic
      algae, and in turn, at deeper river depths, benthic algae can exist only in low
      biomasses which are subsidised by sinking planktonic algae. We generalise the
      spatial dynamics of the model system using different conditions at the upstream
      end of the model, which mimic various natural or anthropogenic factors (pristine
      source, dam, inflow of a waste water treatment plant, and dilution from e.g. a
      tributary) and analyse how these scenarios influence different aspects of the
      longitudinal spatial dynamics of the full spatial model: the relation of spatial
      equilibrium to spatial maximum, the distance to the spatial maximum, and the
      response length. Generally, our results imply that shallow systems recover within
      significantly shorter distances from spatially distinct disturbances when
      compared to deep systems, independent of the type of disturbance.

PMID- 29337263
TI  - iMem-2LSAAC: A two-level model for discrimination of membrane proteins and their
      types by extending the notion of SAAC into chou's pseudo amino acid composition.
AB  - Membrane proteins execute significant roles in cellular processes of living
      organisms, ranging from cell signaling to cell adhesion. As a major part of a
      cell, the identification of membrane proteins and their functional types become a
      challenging job in the field of bioinformatics and proteomics from last few
      decades. Traditional experimental procedures are slightly applicable due to lack
      of recognized structures, enormous time and space. In this regard, the demand for
      fast, accurate and intelligent computational method is increased day by day. In
      this paper, a two-tier intelligent automated predictor has been developed called
      iMem-2LSAAC, which classifies protein sequence as membrane or non-membrane in
      first-tier (phase1) and in case of membrane the second-tier (phase2) identifies
      functional types of membrane protein. Quantitative attributes were extracted from
      protein sequences by applying three discrete features extraction schemes namely
      amino acid composition, pseudo amino acid composition and split amino acid
      composition (SAAC). Various learning algorithms were investigated by using
      jackknife test to select the best one for predictor. Experimental results
      exhibited that the highest predictive outcomes were yielded by SVM in conjunction
      with SAAC feature space on all examined datasets. The true classification rate of
      iMem-2LSAAC predictor is significantly higher than that of other state-of- the-
      art methods so far in the literature. Finally, it is expected that the proposed
      predictor will provide a solid framework for the development of pharmaceutical
      drug discovery and might be useful for researchers and academia.

PMID- 29337264
TI  - Indirect reciprocity with negative assortment and limited information can promote
      cooperation.
AB  - Cooperation is ubiquitous in biological and social systems, even though
      cooperative behavior is often costly and at risk of exploitation by non
      cooperators. Several studies have demonstrated that indirect reciprocity, whereby
      some members of a group observe the behaviors of their peers and use this
      information to discriminate against previously uncooperative agents in the
      future, can promote prosocial behavior. Some studies have shown that differential
      propensities of interacting among and between different types of agents
      (interaction assortment) can increase the effectiveness of indirect reciprocity.
      No previous studies have, however, considered differential propensities of
      observing the behaviors of different types of agents (information assortment).
      Furthermore, most previous studies have assumed that discriminators possess
      perfect information about others and incur no costs for gathering and storing
      this information. Here, we (1) consider both interaction assortment and
      information assortment, (2) assume discriminators have limited information about
      others, and (3) introduce a cost for information gathering and storage, in order
      to understand how the ability of discriminators to stabilize cooperation is
      affected by these steps toward increased realism. We report the following
      findings. First, cooperation can persist when agents preferentially interact with
      agents of other types or when discriminators preferentially observe other
      discriminators, even when they have limited information. Second, contrary to
      intuition, increasing the amount of information available to discriminators can
      exacerbate defection. Third, introducing costs of gathering and storing
      information makes it more difficult for discriminators to stabilize cooperation.
      Our study is one of only a few studies to date that show how negative interaction
      assortment can promote cooperation and broadens the set of circumstances in which
      it is know that cooperation can be maintained.

PMID- 29337265
TI  - 99mTc-vinorelbine tartrate loaded spherulites: Lung disposition study in Sprague
      Dawley rats by gamma scintigraphy.
AB  - Vinorelbine Tartrate (VLB) is the first line chemotherapeutic agent for treatment
      of Non-Small Cell Lung Cancer, whose non-specific distribution causes unwanted
      side effects. The aim of the present investigation was to formulate VLB loaded
      spherulites intended for targeting the lung. Spherulites were composed of
      Soyabean Phosphatidylcholine (SPC), Cholesterol (Chol), Potassium oleate and
      Mannitol. Lipid film prepared using SPC, Chol and Potassium oleate, was dispersed
      in aqueous phase comprising Mannitol and VLB, followed by controlled shearing and
      extrusion. PEGylated Spherulites were prepared by incorporating 1,2-distearoyl-sn
      glycero-3 phosphatidylethanolamine-N-[methoxy poly (ethylene glycol)] (DSPE-PEG
      2000) in the lipid phase. Vesicles were characterized for size, entrapment
      efficiency and drug release. In vitro cell cytotoxicity and apoptosis study were
      performed on A549 cell line. Radiolabeling of VLB was performed by direct
      labeling with reduced technetium-99m. Binding affinity of 99mTc- labelled
      complexes was assessed by diethylenetriaminepenta acetic acid (DTPA) challenge
      test. Biodistribution study was done in Sprague Dawley rats. Dynamic light
      scattering and Transmission electron micrographs confirmed that PEGylated and non
      PEGylated Spherulites were discrete, spherical and exhibited the size range of
      120-130 nm. Non-PEGylated and PEGylated Spherulites had an entrapment efficiency
      of 95.65% and 94.2% respectively. In vitro drug release study indicated VLB plain
      drug solution diffused completely within 24 h, however, Non-PEGylated and
      PEGylated Spherulites showed similar release pattern till 48 h. Results of cell
      line study showed that cells treated with VLB loaded Spherulites showed more
      cytotoxicity and underwent high degree of apoptosis at lower concentration
      compared to the VLB solution. Radiolabeled complex was stable in saline and
      serum, further, DTPA challenge study ensured the high binding strength. Gamma
      Scintigraphy displayed that PEGylated Spherulites were localized within lungs at
      higher concentration than non-PEGylated followed by plain drug.

PMID- 29337266
TI  - Comparison of the in vitro pharmacological profiles of long-acting muscarinic
      antagonists in human bronchus.
AB  - BACKGROUND AND PURPOSE: Long-acting muscarinic antagonists (LAMAs) have been
      recommended for the treatment of chronic obstructive pulmonary disease and (more
      recently) asthma. However, the in vitro pharmacological profiles of the four
      LAMAs currently marketed (tiotropium, umeclidinium, aclidinium and
      glycopyrronium) have not yet been compared (relative to ipratropium) by using the
      same experimental approach. EXPERIMENTAL APPROACH: With a total of 560 human
      bronchial rings, we investigated the antagonists' potency, onset and duration of
      action for inhibition of the contractile response evoked by electrical field
      stimulation. We also evaluated the antagonists' potency for inhibiting cumulative
      concentration-contraction curves for acetylcholine and carbachol. KEY RESULTS:
      The onset and duration of action were concentration-dependent. At submaximal,
      equipotent concentrations, the antagonists' onsets of action were within the same
      order of magnitude. However, the durations of action differed markedly. After
      washout, ipratropium's inhibitory activity decreased rapidly (within 30-90 min)
      but those of tiotropium and umeclidinium remained stable (at above 70%) for at
      least 9 h. Aclidinium and glycopyrronium displayed less stable inhibitory
      effects, with a progressive loss of inhibition at submaximal concentrations. In
      contrast to ipratropium, all the LAMAs behaved as insurmountable antagonists by
      decreasing the maximum responses to both acetylcholine and carbachol. CONCLUSIONS
      AND IMPLICATIONS: The observed differences in the LAMAs' in vitro pharmacological
      profiles in the human bronchus provide a compelling pharmacological rationale for
      the differences in the drugs' respective recommended daily doses and frequencies
      of administration.

PMID- 29337267
TI  - Acute lung injury induced by intestinal ischemia and reperfusion is altered in
      obese female mice.
AB  - RATIONAL: Acute lung injury (ALI) is a common complication after intestinal
      ischemia and reperfusion (I/R) injury that can lead to acute respiratory distress
      syndrome (ARDS). We have previously demonstrated that females are protected
      against lung damage induced by intestinal I/R through an estrogen mediated
      mechanism. OBJECTIVES: To investigate the effect of obesity on ALI induced by
      intestinal I/R in female mice. METHODS: C57Bl/6 female mice were fed with a
      standard low-fat diet (SD) or a high-fat diet (HFD) for 9 weeks. Intestinal I/R
      injury was induced by a 45 min occlusion of the mesenteric artery followed by 2
      and 24 h of reperfusion. RESULTS: Significant increase in lung myeloperoxidase
      expression (MPO) and neutrophil numbers of SD and HFD mice occurred at 2 h and 24
      h of reperfusion. Furthermore, HFD mice presented a significant increase in lung
      eosinophil peroxidase (EPO) expression and eosinophil numbers compared to SD
      mice. Lung wet/dry weight ratio was significantly greater in HFD mice at 2 and 24
      h of reperfusion, accompanied by a significant increase in the expression of
      inducible NO in the lung tissue and a significant decrease in arterial oxygen
      saturation at 24 h of reperfusion relative to SD mice. CONCLUSION: Obesity
      predisposes female mice to increased pulmonary oedema and deterioration in gas
      exchange, which is accompanied by an increase in iNOS expression in the lung.

PMID- 29337268
TI  - The double-sidedness of cough in the elderly.
AB  - Cough is a physiological reflex to protect airways against aspiration, but also
      it is one of the most frequent problems that lead patients to seek medical care.
      Chronic cough is more prevalent in the elderly than younger subjects, and more
      challenging to manage due to frequent comorbidities and possible side effects
      from drug treatment. Meanwhile, cough reflex does not decrease with natural aging
      but is often impaired by pathologic conditions like stroke. The impairment in
      cough reflex may lead to fatal complication like aspiration pneumonia. In this
      paper, we reviewed epidemiology and clinical considerations for chronic cough in
      the elderly, and summarized aging-related changes in cough reflex and also
      possible ways to normalize cough reflex and prevent aspiration pneumonia.

PMID- 29337269
TI  - Inhibitors of phosphodiesterases in the treatment of cough.
AB  - A group of 11 enzyme families of metalophosphohydrolases called
      phosphodiesterases (PDEs) is responsible for a hydrolysis of intracellular cAMP
      and cGMP. Xanthine derivatives (methylxanthines) inhibit PDEs without selective
      action on their single isoforms and lead to many pharmacological effects, e.g.
      bronchodilation, anti-inflammatory and immunomodulating effects, and thus they
      can modulate the cough reflex. Contrary, selective PDE inhibitors have been
      developed to inhibit PDE isoforms with different pharmacological effects based on
      their tissue expression. In this paper, effects of non-selective PDE inhibitors
      (e.g. theophylline) are discussed, with a description of other putative
      mechanisms in their effects on cough. Antitussive effects of selective inhibitors
      of several PDE isoforms are reviewed, focusing on PDE1, PDE3, PDE4, PDE5 and
      PDE7. The inhibition of PDEs suggests participation of bronchodilation,
      suppression of TRPV channels and anti-inflammatory action in cough suppression.
      Selective PDE3, PDE4 and PDE5 inhibitors have demonstrated the most significant
      cough suppressive effects, confirming their benefits in chronic inflammatory
      airway diseases associated with bronchoconstriction and cough.

PMID- 29337270
TI  - The cationic tetradecapeptide mastoparan as a privileged structure for drug
      discovery: Enhanced antimicrobial properties of mitoparan analogues modified at
      position-14.
AB  - Mastoparan (MP) peptides, distributed in insect venoms, induce a local
      inflammatory response post envenomation. Most endogenous MPs share common
      structural elements within a tetradecapeptide sequence that adopts an amphipathic
      helix whilst traversing biological membranes and when bound to an intracellular
      protein target. Rational modifications to increase cationic charge density and
      amphipathic helicity engineered mitoparan (MitP), a mitochondriotoxic bioportide
      and potent secretagogue. Following intracellular translocation, MitP is accreted
      by mitochondria thus indicating additional utility as an antimicrobial agent.
      Hence, the objectives of this study were to compare the antimicrobial activities
      of a structurally diverse set of cationic cell penetrating peptides, including
      both MP and MitP sequences, and to chemically engineer analogues of MitP for
      potential therapeutic applications. Herein, we confirm that, like MP, MitP is a
      privileged structure for the development of antimicrobial peptides active against
      both prokaryotic and eukaryotic pathogens. Collectively, MitP and target
      selective chimeric analogues are broad spectrum antibiotics, with the Gram
      negative A. baumannii demonstrating particular susceptibility. Modifications of
      MitP by amino acid substitution at position-14 produced peptides, Delta14MitP
      analogues, with unique pharmacodynamic properties. One example, [Ser14]MitP,
      lacks both cytotoxicity against human cell lines and mast cell secretory activity
      yet retains selective activity against the encapsulated yeast C. neoformans.

PMID- 29337271
TI  - RFRP-3, the mammalian ortholog of GnIH, induces cell cycle arrest at G2/M in
      porcine ovarian granulosa cells.
AB  - RFamide-related peptide-3 (RFRP-3), the mammalian ortholog of gonadotropin
      inhibitory hormone (GnIH), has been proposed as a key inhibitory regulator of
      mammal reproduction. Our previous studies have demonstrated that RFRP-3 inhibited
      the expression of proliferation-related proteins in porcine granulose cells
      (GCs), but the inhibitory mechanism causing this has not been discovered. Here,
      we aim to elucidate the underlying mechanism and determine the cell cycle
      regulatory sites of action of RFRP-3 on porcine GC proliferation. To this end,
      the viability of porcine GCs was initially estimated by cell counting kit-8 (CCK
      8). We confirmed that different doses of RFRP-3 decreased the cellular viability,
      suggesting that RFRP-3 could inhibit the proliferation of GCs. Subsequently, we
      evaluated the direct effects of RFRP-3 on the expression of cell cycle
      regulators. Compared to the control treated cells, 10-6 and 10-8 M of RFRP-3
      effectively reduced the transcription of Cyclin B1 and CDK1 mRNAs. However,
      treatment with RFRP-3 did not alter Cyclin A2, Cyclin D1, CDK2, or CDK4 mRNA
      levels. These results suggest that RFRP-3 might be inducing G2/M-phase arrest in
      porcine GCs. Finally, to further determine the molecular mechanism underlying
      RFRP-3-mediated G2/M cell cycle arrest, we observed the levels of G2/M cell cycle
      regulatory factors in RFRP-3-treated porcine GCs. The results showed that RFRP-3
      treatment significantly increased the expression of Myt1, p-Wee1 and p-Cdc2,
      whereas the level of Cyclin B1 significantly decreased in porcine GCs treated
      with 10-6 M of RFRP-3. Taken together, our data suggest that RFRP-3 regulates the
      phosphorylation or expression of G2/M cell cycle regulatory factors to induce
      G2/M-phase arrest via inhibition Cyclin B-CDK1 complex activation in porcine GCs,
      which might provide an unfavorable condition for porcine GC proliferation.

PMID- 29337272
TI  - Circulating adipokines and mRNA expression in adipose tissue and the placenta in
      women with gestational diabetes mellitus.
AB  - Maternal adipose tissue and the placenta secrete various molecules commonly
      called adipokines such as chemerin, omentin-1, visfatin, adiponectin, and leptin
      that are important players in the pathogenesis of insulin resistance. Gestational
      diabetes mellitus (GDM) is defined as a state of glucose intolerance
      characterized by beta-cell dysfunction and insulin resistance. To examine whether
      circulating adipokines and their mRNA expression in the adipose tissue and the
      placenta are altered in GDM pregnancy, we compared 15 GDM women [obese (BMI > 30)
      and non-obese (BMI < 30)] to 23 NGT (normal glucose tolerance) women [obese and
      non-obese], at the time of the Cesarean section. Circulating chemerin and leptin
      were higher (p = 0.009 and p = 0.005, respectively) and circulating omentin-1,
      visfatin, as well as the adiponectin/leptin ratio were lower (p = 0.039, p =
      0.007 and p = 0.011, respectively) in GDM-obese compared to NGT-non-obese women.
      Chemerin and leptin correlated positively with BMI and HOMA-IR and omentin-1
      correlated negatively with BMI. Serum TNF-alpha was significantly elevated in all
      obese compared to non-obese pregnant women and correlated positively with BMI.
      Adiponectin levels were reduced -although not significantly- in GDM- and NGT
      obese women compared to their non-obese counterparts. Resistin, RPB4 and IL-6
      levels did not differ significantly between groups. Chemerin mRNA expression in
      subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) was
      significantly higher compared to placenta in all women (6-to 24-times, p < 0.05).
      Chemerin-VAT mRNA expression in GDM-obese tended to be significantly higher
      compared to NGT-non-obese women (3-times, p = 0.005). Omentin-1 mRNA expression
      was significantly higher in VAT compared to SAT (50- to 100-times, p < 0.01) and
      its expression in placenta was negligible in all women. Although, leptin was
      expressed significantly higher in SAT compared to VAT and the placenta in all
      women (5- to 46-times, p < 0.05), only its mRNA expression in VAT of obese (GDM
      and NGT) differed significantly when compared to NGT-non-obese women (3-times
      higher, p < 0.02). Visfatin mRNA expression was comparable in all tissues. In
      conclusion, chemerin and leptin are elevated and omentin-1 and visfatin levels
      are decreased in GDM women complicated by obesity. This finding together with the
      positive association of chemerin and leptin with markers of insulin resistance,
      suggests that these adipokines and more especially chemerin and leptin
      accompanied by their adipose tissue expression could contribute to the increased
      insulin resistance and low grade inflammation that characterizes GDM-obese women.

PMID- 29337273
TI  - Identification of epistatic mutations and insights into the evolution of the
      influenza virus using a mass-based protein phylogenetic approach.
AB  - A mass-based protein phylogenetic approach developed in this laboratory has been
      applied to study mutation trends and identify consecutive or near-consecutive
      mutations typically associated with positive epistasis. While epistasis is
      thought to occur commonly during the evolution of viruses, the extent of
      epistasis in influenza, and its role in the evolution of immune escape and drug
      resistant mutants, remains to be systematically investigated. Here putative
      epistatic mutations within H3 hemagglutinin in type A influenza are identified
      where leading parent mutations were found to predominate within reported
      antigenic sites of the protein. Frequent subsequent mutations resided exclusively
      in different antigenic regions, providing the virus with a possible immune escape
      mechanism, or at other remote sites that drive beneficial protein structural and
      functional change. The results also enable a "small steps" evolutionary model to
      be proposed where the more frequent consecutive, or near-consecutive, non
      conservative mutations exhibited less structural, and thus functional, change.
      This favours the evolutionary survival of the virus over mutations associated
      with more substantive change that may cause or risk its own extinction.

PMID- 29337274
TI  - Species delimitation of the North American orchard-spider Leucauge venusta
      (Walckenaer, 1841) (Araneae, Tetragnathidae).
AB  - The orchard spider, Leucauge venusta (Walckenaer, 1841) is one of the most common
      and abundant orb-weavers in North America. This species has a broad geographic
      distribution extending across tropical and temperate regions of the Americas from
      Canada to Brazil. Guided by a preliminary observation of the barcode gap between
      sequences from specimens of L. venusta collected in Florida and other North
      American localities, we collected across a transect through the southeastern USA
      to investigate the observed genetic divide. The dataset, complemented with
      additional samples from Mexico, and Brazil was analyzed for species delimitation
      using STACEY and bGMYC based on sequences from one nuclear (ITS2) and one
      mitochondrial marker (COI). The analyses clearly separate USA samples into two
      deeply divergent and geographically structured groups (north-south) which we
      interpret as two different species. We generated ecological niche models for
      these two groups rejecting a niche equivalence hypothesis for these lineages.
      Taxonomic changes are proposed based on these findings, Leucauge venusta is
      restricted to denote the northern clade, and its known distribution restricted to
      the USA. Leucauge argyrobapta (White, 1841) is removed from synonymy to denote
      the populations in Florida, Mexico and Brazil. Although the delimitation analyses
      suggest each of these geographic clusters within the L. argyrobapta samples
      represent different species, more specimens from Central and South America are
      needed to properly test the cohesion of L. argyrobapta populations.

PMID- 29337275
TI  - The O-beta-linked N-acetylglucosaminylation of the Lamin B receptor and its
      impact on DNA binding and phosphorylation.
AB  - : Lamin B Receptor (LBR) is an integral protein of the interphase inner nuclear
      membrane that is implicated in chromatin anchorage to the nuclear envelope.
      Phosphorylation of a stretch of arginine-serine (RS) dipeptides in the amino
      terminal nucleoplasmic domain of LBR regulates the interactions of the receptor
      with other nuclear proteins, DNA and RNA and thus modulates tethering of
      heterochromatin to the nuclear envelope. While phosphorylation has been
      extensively studied, very little is known about other post-translational
      modifications of the protein. There is only one report on the O-beta-linked N
      acetyl-glucosaminylation (O-GlcNAcylation) of a serine residue downstream of the
      RS domain of rat LBR. In the present study we identify additional O-GlcNAcylation
      sites by using as substrates of O-beta-N-acetylglucosaminyltransferase (OGT) a
      set of peptides containing the entire LBR RS domain or parts of it as well as
      flanking sequences. The in vitro activity of OGT was assessed by tandem mass
      spectrometry and NMR spectroscopy. Furthermore, we provide evidence that O
      GlcNAcylation hampers DNA binding while it marginally affects RS domain
      phosphorylation mediated by SRPK1, Akt2 and cdk1 kinases. GENERAL SIGNIFICANCE:
      Our methodology providing a quantitative description of O-GlcNAc patterns based
      on a combination of mass spectrometry and high resolution NMR spectroscopy on
      short peptide substrates allows subsequent functional analyses. Hence, our
      approach is of general interest to a wide audience of biologists aiming at
      deciphering the functional role of O-GlcNAc glycosylation and its crosstalk with
      phosphorylation.

PMID- 29337276
TI  - Validation of diffusion MRI estimates of compartment size and volume fraction in
      a biomimetic brain phantom using a human MRI scanner with 300 mT/m maximum
      gradient strength.
AB  - Diffusion microstructural imaging techniques have attracted great interest in the
      last decade due to their ability to quantify axon diameter and volume fraction in
      healthy and diseased human white matter. The estimates of compartment size and
      volume fraction continue to be debated, in part due to the lack of a gold
      standard for validation and quality control. In this work, we validate diffusion
      MRI estimates of compartment size and volume fraction using a novel textile axon
      ("taxon") phantom constructed from hollow polypropylene yarns with distinct intra
      and extra-taxonal compartments to mimic white matter in the brain. We acquired a
      comprehensive set of diffusion MRI measurements in the phantom using multiple
      gradient directions, diffusion times and gradient strengths on a human MRI
      scanner equipped with maximum gradient strength (Gmax) of 300 mT/m. We obtained
      estimates of compartment size and restricted volume fraction through a
      straightforward extension of the AxCaliber/ActiveAx frameworks that enables
      estimation of mean compartment size in fiber bundles of arbitrary orientation.
      The voxel-wise taxon diameter estimates of 12.2 +/- 0.9 MUm were close to the
      manufactured inner diameter of 11.8 +/- 1.2 MUm with Gmax = 300 mT/m. The
      estimated restricted volume fraction demonstrated an expected decrease along the
      length of the fiber bundles in accordance with the known construction of the
      phantom. When Gmax was restricted to 80 mT/m, the taxon diameter was
      overestimated, and the estimates for taxon diameter and packing density showed
      greater uncertainty compared to data with Gmax = 300 mT/m. In conclusion, the
      compartment size and volume fraction estimates resulting from diffusion
      measurements on a human scanner were validated against ground truth in a phantom
      mimicking human white matter, providing confidence that this method can yield
      accurate estimates of parameters in simplified but realistic microstructural
      environments. Our work also demonstrates the importance of a biologically
      analogous phantom that can be applied to validate a variety of diffusion
      microstructural imaging methods in human scanners and be used for standardization
      of diffusion MRI protocols for neuroimaging research.

PMID- 29337277
TI  - Compensatory dopaminergic-cholinergic interactions in conflict processing:
      Evidence from patients with Parkinson's disease.
AB  - Executive functions are complex both in the cognitive operations involved and in
      the neural structures and functions that support those operations. This
      complexity makes executive function highly vulnerable to the detrimental effects
      of aging, brain injury, and disease, but may also open paths to compensation.
      Neural compensation is often used to explain findings of additional or altered
      patterns of brain activations by older adults or patient populations compared to
      young adults or healthy controls, especially when associated with relatively
      preserved performance. Here we test the hypothesis of an alternative form of
      compensation, between different neuromodulator systems. 135 patients with
      Parkinson's Disease (PD) completed vesicular monoamine transporter type2 (VMAT2)
      and acetylcholinesterase PET scanning to assess the integrity of nigrostriatal
      dopaminergic, thalamic cholinergic, and cortical cholinergic pathways, and a
      behavioral test (Stroop + task-switching) that puts high demands on conflict
      processing, an important aspect of executive control. Supporting the compensatory
      hypothesis, regression models controlling for age and other covariates revealed
      an interaction between caudate dopamine and cortical cholinergic integrity:
      Cortical cholinergic integrity was a stronger predictor of conflict processing in
      patients with relatively low caudate dopaminergic function. These results suggest
      that although frontostriatal dopaminergic function plays a central role in
      executive control, cholinergic systems may also make an important contribution.
      The present results suggest potential pathways for remediation, and that the
      appropriate interventions for each patient may depend on their particular profile
      of decline. Furthermore, they help to elucidate the brain systems that underlie
      executive control, which may be important for understanding other disorders as
      well as executive function in healthy adults.

PMID- 29337278
TI  - Effects of hunger state on the brain responses to food cues across the life span.
AB  - The abundant exposure to food cues in our environment is one of the main drivers
      of overconsumption. Food evaluation is important for the regulation of food
      intake by the brain and it's interaction with hunger state. Children are
      especially susceptible to food cues. Understanding the mechanisms behind this
      regulation in healthy individuals across the life span can help to elucidate the
      mechanisms underlying overconsumption and aid the development of future obesity
      prevention strategies. Few functional neuroimaging studies have been done in
      children and elderly. Furthermore, it is unknown how hunger state affects neural
      food cue reactivity in these groups, since this has not been examined
      consistently. We examined the effects of hunger state and age on the brain
      responses to low- and high calorie foods. On two mornings, 122 participants (17
      children; 38 teens; 36 adults; 31 elderly) performed a food image viewing task
      while being scanned using fMRI, either fasted or sated. Hunger induced greater
      activation during high versus low calorie food image viewing than satiety in the
      bilateral dorsomedial (dmPFC) and in the right dorsolateral prefrontal cortex
      (dlPFC) across all age groups. There was no significant main effect of age group
      on high versus low calorie food image viewing and no interaction between age
      group and hunger state. The greater activation of the dlPFC across all age groups
      during high calorie food image viewing in a fasted state might reflect increased
      inhibitory control in response to these foods. This may underlie the ability to
      resist overconsumption of high calorie foods. Furthermore, increased medial
      prefrontal cortex activation during hunger might reflect increased reward value
      of high calorie foods, which declines with satiation. Further studies are needed
      to better understand these results. Notably, overweight and obese individuals
      should be included to examine whether these responses are altered by weight
      status across the life span.

PMID- 29337279
TI  - Suprathreshold fiber cluster statistics: Leveraging white matter geometry to
      enhance tractography statistical analysis.
AB  - This work presents a suprathreshold fiber cluster (STFC) method that leverages
      the whole brain fiber geometry to enhance statistical group difference analyses.
      The proposed method consists of 1) a well-established study-specific data-driven
      tractography parcellation to obtain white matter tract parcels and 2) a newly
      proposed nonparametric, permutation-test-based STFC method to identify
      significant differences between study populations. The basic idea of our method
      is that a white matter parcel's neighborhood (nearby parcels with similar white
      matter anatomy) can support the parcel's statistical significance when correcting
      for multiple comparisons. We propose an adaptive parcel neighborhood strategy to
      allow suprathreshold fiber cluster formation that is robust to anatomically
      varying inter-parcel distances. The method is demonstrated by application to a
      multi-shell diffusion MRI dataset from 59 individuals, including 30 attention
      deficit hyperactivity disorder patients and 29 healthy controls. Evaluations are
      conducted using both synthetic and in-vivo data. The results indicate that the
      STFC method gives greater sensitivity in finding group differences in white
      matter tract parcels compared to several traditional multiple comparison
      correction methods.

PMID- 29337281
TI  - Clinical Significance of Early Fluid and Weight Change During Acute Heart Failure
      Hospitalization.
AB  - AIMS: To explore the association of changes in weight and fluid during treatment
      for acute heart failure (AHF) with clinical endpoints. METHODS AND RESULTS:
      Weight and net fluid changes recorded at 72-96 hours in 708 AHF patients enrolled
      in Diuretic Optimization Strategy Evaluation in Acute Decompensated Heart
      Failure, Cardiorenal Rescue Study in Acute Decompensated Heart Failure, and Renal
      Optimization Strategies Evaluation in Acute Heart Failure studies were compared
      with freedom from congestion at 72-96 hours and a composite endpoint of death,
      rehospitalization, and unplanned hospital visit at 60 days. Weight loss was
      concordant with net fluid loss in 55%, discordant and less than expected for
      fluid loss in 34%, and paradoxically discordant or more than expected for fluid
      loss in 11% of patients. Weight loss, but not fluid loss, was associated with
      freedom from congestion (odds ratio per 1-kg weight loss = 1.11 [1.03-1.19]) and
      a nominal reduction in the composite endpoint (hazard ratio per 1-kg weight loss
      = 0.98 [0.95-1.00]). Outcomes were similar in patients with concordant and
      discordant weight-fluid loss. CONCLUSION: During treatment for AHF, early changes
      in weight may be more useful for identifying response to therapy and for
      predicting outcomes than net fluid output. Nearly one-half of patients receiving
      decongestive therapies demonstrate discordant changes in weight and fluid;
      however, discordance was not associated with outcomes.

PMID- 29337280
TI  - Behavioral interventions for reducing head motion during MRI scans in children.
AB  - A major limitation to structural and functional MRI (fMRI) scans is their
      susceptibility to head motion artifacts. Even submillimeter movements can
      systematically distort functional connectivity, morphometric, and diffusion
      imaging results. In patient care, sedation is often used to minimize head motion,
      but it incurs increased costs and risks. In research settings, sedation is
      typically not an ethical option. Therefore, safe methods that reduce head motion
      are critical for improving MRI quality, especially in high movement individuals
      such as children and neuropsychiatric patients. We investigated the effects of
      (1) viewing movies and (2) receiving real-time visual feedback about head
      movement in 24 children (5-15 years old). Children completed fMRI scans during
      which they viewed a fixation cross (i.e., rest) or a cartoon movie clip, and
      during some of the scans they also received real-time visual feedback about head
      motion. Head motion was significantly reduced during movie watching compared to
      rest and when receiving feedback compared to receiving no feedback. However,
      these results depended on age, such that the effects were largely driven by the
      younger children. Children older than 10 years showed no significant benefit. We
      also found that viewing movies significantly altered the functional connectivity
      of fMRI data, suggesting that fMRI scans during movies cannot be equated to
      standard resting-state fMRI scans. The implications of these results are twofold:
      (1) given the reduction in head motion with behavioral interventions, these
      methods should be tried first for all clinical and structural MRIs in lieu of
      sedation; and (2) for fMRI research scans, these methods can reduce head motion
      in certain groups, but investigators must keep in mind the effects on functional
      MRI data.

PMID- 29337282
TI  - Comparative proteome analysis of monolayer and spheroid culture of canine
      osteosarcoma cells.
AB  - : Osteosarcoma is an aggressive bone tumor with high metastasis rate in the lungs
      and affects both humans and dogs in a similar way. Three-dimensional tumor cell
      cultures mimic the in vivo situation of micro-tumors and metastases and are
      therefore better experimental in vitro models than the often applied two
      dimensional monolayer cultures. The aim of the present study was to perform
      comparative proteomics of standard monolayer cultures of canine osteosarcoma
      cells (D17) and three-dimensional spheroid cultures, to better characterize the
      3D model before starting with experiments like migration assays. Using DIGE in
      combination with MALDI-TOF/TOF we found 27 unique canine proteins differently
      represented between these two culture systems, most of them being part of a
      functional network including mainly chaperones, structural proteins, stress
      related proteins, proteins of the glycolysis/gluconeogenesis pathway and
      oxidoreductases. In monolayer cells, a noticeable shift to more acidic pI values
      was noticed for several proteins of medium to high abundance; two proteins
      (protein disulfide isomerase A3, stress-induced-phosphoprotein 1) showed an
      increase of phosphorylated protein species. Protein distribution within the
      cells, as detected by immunohistochemistry, displayed a switch of stress-induced
      phosphoprotein 1 from the cytoplasm (in monolayer cultures) to the nucleus (in
      spheroid cultures). Additionally, Western blot testing revealed upregulated
      concentrations of metastasin (S100A4), triosephosphate isomerase 1 and septin 2
      in spheroid cultures, in contrast to decreased concentrations of CCT2, a subunit
      of the T-complex. Results indicate regulation of stress proteins in the process
      of three-dimensional organization characterized by a hypoxic and nutrient
      deficient environment comparable to tumor micro-metastases. SIGNIFICANCE:
      Osteosarcoma is an aggressive bone tumor that early spreads to the lungs. Three
      dimensional tumor cell cultures represent the avascular stage of micro-tumors and
      metastases, and should therefore represent a better experimental in vitro model
      compared to two-dimensional monolayer cultures. Significant differences have been
      reported in response to drug and radiation treatment between these two culture
      systems. A gel-based proteomic investigation was performed to compare protein
      patterns of a canine osteosarcoma cell line cultivated under those two
      conditions, to learn more about altered cell composition and its impact on cell
      behaviour. Due to the fact that the canine osteosarcoma is an accepted model for
      the human disease, results will be relevant for the human species as well.

PMID- 29337283
TI  - Variability studies of allochthonous stone pine (Pinus pinea L.) plantations in
      Chile through nut protein profiling.
AB  - : Stone pine (Pinus pinea) is characterized by low differentiation of growth
      parameters, high phenotypic plasticity and low genetic variability; detecting its
      diversity in introduced Chilean populations is therefore relevant for
      conservation and breeding programs. Here, variability among allochthonous Stone
      pine populations in Chile was explored using electrophoresis-based proteomic
      analysis of pine nuts. Cones from 30 populations distributed along a climatic
      gradient in Chile were surveyed and sampled, and proteins were extracted from
      seed flour using the TCA-acetone precipitation protocol. Extracts were subjected
      to SDS-PAGE and 2-DE for protein resolution, gel images captured, and spot or
      bands intensity quantified and subjected to statistical analysis (ANOVA,
      unsupervised Hierarchical Analysis Clustering and PLS regression). Protein yield
      ranged among populations from 161.7 (North populations) to 298.7 (South
      populations) mg/g dry weight. A total of 50 bands were resolved by SDS-PAGE in
      the 6.5-200 kDa Mr. range, of which 17 showed quantitative or qualitative
      differences, with 12 proteins identified. Pine nut extracts from the most distant
      populations were analyzed by 2-DE and a total of 129 differential spots were
      observed, out of which 13 were proposed as putative protein markers of
      variability. Out of the 129 spots, 118 proteins were identified after MALDI
      TOF/TOF analysis. Identified proteins were classified into two principal
      categories: reserve and stress related. We provide the first protein map of P.
      pinea nuts. The use of a proteomic approach was useful to detect variability of
      Stone pine across three Chilean macrozones, with correlations between protein
      profiles and geoclimatic parameters, suggesting a new approach to study the
      variability of this species. BIOLOGICAL SIGNIFICANCE: This study presents the
      first protein map of Stone pine nuts, relevant for the advancement of protein
      characterization in pine nuts. Putative protein markers are proposed, evidencing
      that a proteomic approach may be useful to detect variability of Stone pine
      across Chilean macrozones, suggesting a new approach to study the variability of
      this species, which may also be extrapolated to other forest fruit species.

PMID- 29337284
TI  - Method for identification of sensitive nodes in Boolean models of biological
      networks.
AB  - Biological systems are often represented as Boolean networks and analysed to
      identify sensitive nodes which on perturbation disproportionately change a
      predefined output. There exist different kinds of perturbation methods:
      perturbation of function, perturbation of state and perturbation in update
      scheme. Nodes may have defects in interpretation of the inputs from other nodes
      and calculation of the node output. To simulate these defects and systematically
      assess their effect on the system output, two new function perturbations,
      referred to as 'not of function' and 'function of not', are introduced. In the
      former, the inputs are assumed to be correctly interpreted but the output of the
      update rule is perturbed; and in the latter, each input is perturbed but the
      correct update rule is applied. These and previously used perturbation methods
      were applied to two existing Boolean models, namely the human melanogenesis
      signalling network and the fly segment polarity network. Through mathematical
      simulations, it was found that these methods successfully identified nodes
      earlier found to be sensitive using other methods, and were also able to identify
      sensitive nodes which were previously unreported.

PMID- 29337285
TI  - Comparison of clustering approaches with application to dual colour protein data.
AB  - Cells communicate with their environment via proteins, located at the plasma
      membrane separating the interior of a cell from its surroundings. The spatial
      distribution of these proteins in the plasma membrane under different
      physiological conditions is of importance, since this may influence their signal
      transmission properties. In this study, the authors compare different methods
      such as hierarchical clustering, extensible Markov models and the gammics method
      for analysing such a spatial distribution. The methods are examined in a
      simulation study to determine their optimal use. Afterwards, they analyse
      experimental imaging data and extend these methods to simulate dual colour data.

PMID- 29337286
TI  - Estimation of parameters for plasma glucose regulation in type-2 diabetics in
      presence of meal.
AB  - In this study, the authors propose a methodology for the estimation of glucose
      masses in stomach (both in solid and liquid forms), intestine, plasma and tissue;
      insulin masses in portal vein, liver, plasma and interstitial fluid using only
      plasma glucose measurement. The proposed methodology fuses glucose-insulin
      homoeostasis model (in the presence of meal intake) and plasma glucose
      measurement with a Bayesian non-linear filter. Uncertainty of the model over
      individual variations has been incorporated by adding process noise to the
      homoeostasis model. The estimation is carried out over 24 h for the healthy
      people as well as a type II diabetes mellitus patients. In simulation, the
      estimator follows the truth accurately for both the cases. Moreover, the
      performances of two non-linear filters, namely the unscented Kalman filter (KF)
      and cubature quadrature KF are compared in terms of root mean square error. The
      proposed methodology will be helpful in future to: (i) observe a patient's
      insulin-glucose profile, (ii) calculate drug dose for any hyperglycaemic patients
      and (iii) develop a closed-loop controller for automated insulin delivery system.

PMID- 29337287
TI  - Revealing determinants of two-phase dynamics of P53 network under gamma
      irradiation based on a reduced 2D relaxation oscillator model.
AB  - This study proposes a two-dimensional (2D) oscillator model of p53 network, which
      is derived via reducing the multidimensional two-phase dynamics model into a
      model of ataxia telangiectasia mutated (ATM) and Wip1 variables, and studies the
      impact of p53-regulators on cell fate decision. First, the authors identify a 6D
      core oscillator module, then reduce this module into a 2D oscillator model while
      preserving the qualitative behaviours. The introduced 2D model is shown to be an
      excitable relaxation oscillator. This oscillator provides a mechanism that leads
      diverse modes underpinning cell fate, each corresponding to a cell state. To
      investigate the effects of p53 inhibitors and the intrinsic time delay of Wip1 on
      the characteristics of oscillations, they introduce also a delay differential
      equation version of the 2D oscillator. They observe that the suppression of p53
      inhibitors decreases the amplitudes of p53 oscillation, though the suppression
      increases the sustained level of p53. They identify Wip1 and P53DINP1 as possible
      targets for cancer therapies considering their impact on the oscillator,
      supported by biological findings. They model some mutations as critical changes
      of the phase space characteristics. Possible cancer therapeutic strategies are
      then proposed for preventing these mutations' effects using the phase space
      approach.

PMID- 29337288
TI  - Network-based method for detecting dysregulated pathways in glioblastoma cancer.
AB  - The knowledge on the biological molecular mechanisms underlying cancer is
      important for the precise diagnosis and treatment of cancer patients. Detecting
      dysregulated pathways in cancer can provide insights into the mechanism of cancer
      and help to detect novel drug targets. Based on the wide existing mutual
      exclusivity among mutated genes and the interrelationship between gene mutations
      and expression changes, this study presents a network-based method to detect the
      dysregulated pathways from gene mutations and expression data of the glioblastoma
      cancer. First, the authors construct a gene network based on mutual exclusivity
      between each pair of genes and the interaction between gene mutations and
      expression changes. Then they detect all complete subgraphs using CFinder
      clustering algorithm in the constructed gene network. Next, the two gene sets
      whose overlapping scores are above a specific threshold are merged. Finally, they
      obtain two dysregulated pathways in which there are glioblastoma-related multiple
      genes which are closely related to the two subtypes of glioblastoma. The results
      show that one dysregulated pathway revolving around epidermal growth factor
      receptor is likely to be associated with the primary subtype of glioblastoma, and
      the other dysregulated pathway revolving around TP53 is likely to be associated
      with the secondary subtype of glioblastoma.

PMID- 29337289
TI  - Antioxidant activity of hydrated carboxylated nanodiamonds and its influence on
      water gamma-radiolysis.
AB  - Water radiolysis involves chemical decomposition of the water molecule into free
      radicals after exposure to ionizing radiation. These free radicals have
      deleterious effects on normal cell physiology. Carboxylated nanodiamonds (cNDs)
      appear to modulate the deleterious effects of gamma-irradiation on the
      pathophysiology of red blood cells (RBCs). In the present work, the antioxidant
      activity of hydrated cNDs (h-cNDs) on limiting oxidative damage (the water
      radiolysis effect) by gamma-irradiation was confirmed. Our results show that h
      cNDs have remarkable free radical scavenging ability and preserve the enzymatic
      activity of catalase after gamma-irradiation. The underlying mechanism through
      which nanodiamonds exhibit antioxidant activity appears to depend on their
      colloidal stability. This property of detonation synthesized nanodiamonds is
      improved after carboxylation, which in turn influences changes in the hydrogen
      bond strength in water. The observed stability of h-cNDs in water and their
      antioxidant activity correlates with their protective effect on RBCs against
      gamma-irradiation.

PMID- 29337290
TI  - Threefold growth efficiency improvement of silica nanosprings by using silica
      nanosprings as a substrate.
AB  - The growth efficiency of one-dimension (1D) nanostructures via the vapor-liquid
      solid process is commonly attributed to parameters such as precursor vapor
      pressure, substrate temperature, and the choice of the catalyst. The work
      presented herein is an investigation of the use of silica nanosprings (SNs) as a
      3D substrate for improving the growth efficiency of SN themselves. SNs are a 1D
      nanomaterial that form a nonwoven structure with optimal geometric
      characteristics and surface properties that mitigate collisions between growing
      nanosprings and ripening of the gold catalyst, which should improve SN yield.
      Nanospring growth, for an eight hour period, on an SN coated surface relative to
      an equivalent flat substrate increased from ~25 mgh-1 to ~80 mgh-1, respectively.
      All things being equal, by splitting the typical amount of catalyst, in this case
      gold, between the first and second growth, the double growth procedure produced
      more than three times more nanosprings than the equivalent single growth of a SN.
      In addition, using an SN as a substrate increased the sustained growth condition
      from four to eight hours, and thus increased by a factor of ten the gravimetric
      yield of SNs relative to the mass of gold used.

PMID- 29337291
TI  - Realization of a half-metallic state on bilayer WSe2 using doping transition
      metals (Cr, Mn, Fe, Co, Ni) in its interlayer.
AB  - The structural, electronic and magnetic properties of Cr, Mn, Fe, Co and Ni-doped
      bilayer WSe2 are predicted by using first principles calculations. The doped
      transition-metal (TM) atoms show a covalent-binding with the nearest Se atoms.
      The calculated electronic structures reveal that the TM Cr, Mn, Fe and Co-doped
      bilayer WSe2 exhibits a half-metallic character with a 100% spin polarization at
      the Fermi level, and the reason is ascribed to the strong hybridization peak
      between the transition metals and the parent W and Se atoms. The Ni-doped bilayer
      WSe2 is still a semiconductor with nonmagnetism. The Fe-doped system has a robust
      stability of half-metallicity because there are three connected states peak
      spanning the Fermi level. The doping of Cr, Mn, Fe and Co atoms leads to a
      prominent total magnetism (0.93-3.65 [Formula: see text] moment per unit cell),
      and an induced ~0.3 [Formula: see text] moment in parent W atoms is found in
      addition to the main contribution of TM atomic magnetism (0.71-3.33 [Formula: see
      text] moment per atom). The predicted Cr, Mn, Fe and Co-doped bilayer WSe2 should
      be the candidate materials for spintronic devices due to their magnetic and half
      metallic nature.

PMID- 29337292
TI  - A rapid, ratiometric, enzyme-free, and sensitive single-step miRNA detection
      using three-way junction based FRET probes.
AB  - MicroRNAs (miRNAs) are single stranded endogenous molecules composed of only 18
      24 nucleotides which are critical for gene expression regulating the translation
      of messenger RNAs. Conventional methods based on enzyme-assisted nucleic acid
      amplification techniques have many problems, such as easy contamination, high
      cost, susceptibility to false amplification, and tendency to have sequence
      mismatches. Here we report a rapid, ratiometric, enzyme-free, sensitive, and
      highly selective single-step miRNA detection using three-way junction assembled
      (or self-assembled) FRET probes. The developed strategy can be operated within
      the linear range from subnanomolar to hundred nanomolar concentrations of miRNAs.
      In comparison with the traditional approaches, our method showed high sensitivity
      for the miRNA detection and extreme selectivity for the efficient discrimination
      of single-base mismatches. The results reveal that the strategy paved a new
      avenue for the design of novel highly specific probes applicable in diagnostics
      and potentially in microscopic imaging of miRNAs in real biological environments.

PMID- 29337293
TI  - A-TEEM<sup>TM</sup>, a New Molecular Fingerprinting Technique: Simultaneous
      Absorbance-Transmission and Fluorescence Excitation-Emission Matrix Method.
AB  - We investigate the new simultaneous Absorbance-Transmission and fluorescence
      Excitation-Emission Matrix method for rapid and effective characterization of the
      varying components from a mixture. The Absorbance-Transmission and fluorescence
      Excitation-Emission Matrix method uniquely facilitates correction of fluorescence
      inner-filter effects to yield quantitative fluorescence spectral information that
      is largely independent of component concentration. This is significant because it
      allows one to effectively monitor quantitative component changes using
      multivariate methods and to generate and evaluate spectral libraries. &#13; We
      present the use of this novel instrument in different fields: i.e. tracking
      changes in complex mixtures including natural water, wine as well as monitoring
      stability and aggregation of hormones for biotherapeutics.&#13.

PMID- 29337294
TI  - Large Area Few Layers Hexagonal Boron Nitride Prepared by Quadrupole Field Aided
      Exfoliation.
AB  - A quadrupole electric field mediated exfoliation method is proposed to convert
      micron sized hexagonal boron nitride (hBN) powders into few layers hexagonal
      boron nitride nano-sheets (h-BNNS). Under the optimum conditions (400 Hz, 40 V,
      32MUg/mL, sodium deoxycholate, TAE medium), the hBN powders (thickness > 200 nm,
      horizontal scale ~ 10 MUm) are successfully exfoliated into 0.5-4 nm (1-10
      layers) thick h-BNNS with the same horizontal scale. Dynamic laser scattering
      (DLS) and atomic force microscope (AFM) statistics show that the yield is 47.6 %
      (for the portion with the thickness of 0.5-6 nm), and all of the vertical sizes
      are reduced to smaller than 18 nm (45 layers).

PMID- 29337295
TI  - How to manipulate magnetic states of antiferromagnets.
AB  - Antiferromagnetic materials, which have drawn considerable attention recently,
      have fascinating features: they are robust against perturbation, produce no stray
      fields, and exhibit ultrafast dynamics. Discerning how to efficiently manipulate
      the magnetic state of an antiferromagnet is key to the development of
      antiferromagnetic spintronics. In this review, we introduce four main methods
      (magnetic, strain, electrical, and optical) to mediate the magnetic states and
      elaborate on intrinsic origins of different antiferromagnetic materials. Magnetic
      control includes a strong magnetic field, exchange bias, and field cooling, which
      are traditional and basic. Strain control involves the magnetic anisotropy effect
      or metamagnetic transition. Electrical control can be divided into two parts,
      electric field and electric current, both of which are convenient for practical
      applications. Optical control includes thermal and electronic excitation, an
      inertia-driven mechanism, and terahertz laser control, with the potential for
      ultrafast antiferromagnetic manipulation. This review sheds light on effective
      usage of antiferromagnets and provides a new perspective on antiferromagnetic
      spintronics.

PMID- 29337296
TI  - Computer analysis of histopathological images for tumor grading.
AB  - OBJECTIVE: We developed a new method that enables automatic and rapid assessment
      of a tumor's proliferation index from immunohistochemically (IHC) stained
      microscopic images. APPROACH: The method is based on computer-aided analysis of
      images - color filtration pixel-by-pixel (CFPP method) of the whole
      histopathological virtual slides. MAIN RESULTS: The method is simple, rapid, and
      does not require the time consuming step of selecting manually areas of interest
      nor the need for computationally complicated detection of hot-spots, both of
      which attempt to emulate a pathologist's way of estimating a proliferation index.
      We apply our method to a set of diffuse large B-cell lymphoma (DLBCL) slide
      images. SIGNIFICANCE: By appropriate changes in the color filtration thresholds,
      our method may be adapted to the analysis of other types of tumors. It may also
      be adapted for analysis of microscopic images in neuropathology, like biopsies of
      dystrophic muscles. Because of its simplicity and rapidity it may also be applied
      for analysis of series of images to assess dynamics of image complexity in
      network physiology.

PMID- 29337297
TI  - 3D hierarchical Ag nanostructures formed on poly(acrylic acid) brushes grafted
      graphene oxide as promising SERS substrates.
AB  - In this study, in situ generation of Ag nanostructures with various morphology on
      poly(acrylic acid) (PAA) brushes grafted onto graphene oxide (GO), for use as
      substrates for surface-enhanced Raman scattering (SERS), is demonstrated. The
      overall synthetic strategy involves the loading of Ag precursor ions ((Ag+ and
      [Ag(NH3)2]+) onto PAA brush-grafted GO, followed by their in situ reduction to Ag
      nanostructures of various morphology using a reducing agent (NaBH4 or ascorbic
      acid). Novel 3D hierarchical flowerlike Ag nanostructures were obtained by using
      AgNO3 as precursor and ascorbic acid as reducing agent. Using 4-aminothiophenol
      as probe molecules, the as-prepared hierarchical Ag nanostructures exhibited
      excellent SERS performance, providing enhancement factors of ~107.

PMID- 29337298
TI  - Tuning the electrical transport of type II Weyl semimetal WTe<sub>2</sub>
      nanodevices by Mo doping.
AB  - We fabricated nanodevices of Mo<sub>x</sub>W<sub>1-x</sub>Te<sub>2</sub> (x =0,
      0.07, 0.35) and conducted systematic comparative study of their electrical
      transport. Magnetoresistance measurements show that Mo doping can significantly
      suppress the mobility and magnetoresistance. The results for the analysis of two
      band model (TBM) show that the doping of Mo does not break the carrier balance.
      By Shubnikov-de Haas oscillations (SdHO) analysis, we found that Mo doping also
      has a strong suppress on the quantum oscillation of the sample, and the higher
      the ratio of Mo is, the fewer the pockets observed in our experiments are.
      Furthermore, with the increase of Mo ratio, the effective mass of electron and
      hole increases gradually, while the corresponding quantum mobility decreases
      rapidly.

PMID- 29337299
TI  - Comparison of acrylic polymer adhesive tapes and silicone optical grease in light
      sharing detectors for positron emission tomography.
AB  - Optical coupling is an important factor in detector design as it improves optical
      photon transmission by mitigating internal reflections at light-sharing
      boundaries. In this work we compare optical coupling materials, namely double
      sided acrylic polymer tapes and silicone optical grease (SiG), in the context of
      positron emission tomography. Four double-sided tapes from 3 M of varying
      thicknesses (0.229 mm-1.016 mm) and adhesive materials ('100MP', 'A100', and
      'GPA') were characterized with spectrophotometer measurements as well as
      photopeak amplitude and energy resolution measurements using lutetium-yttrium oxy
      orthosilicate (LYSO) coupled to photomultiplier tubes (PMT) or silicon
      photomultipliers (SiPMs). Transmission spectra from the spectrophotometer showed
      over 80% transmission for all tapes at 420 nm and above, with 89.6% and 88.8%
      transmission for the 0.508 mm and 1.016 mm thick GPA tapes, respectively, at 420
      nm. Measurements with single-pixel LYSO-PMT and 4  *  4 array (one-to-one
      coupled) LYSO-SiPM setups determined that SiG had the greatest photopeak
      amplitude, with tapes showing 2.1%-14.8% reduction in photopeak amplitude with
      respect to SiG. Energy resolution changed by less than 4% on a relative basis
      between tapes and SiG with PMT measurements, however for the SiPM array
      measurements the energy resolution improved from 15.6%  +/-  2.7% full-width at
      half-maximum to 11.4%  +/-  1.2% for SiG and 1 mm GPA respectively. Data acquired
      with dual-layer offset LYSO arrays (light sharing detector designs) demonstrated
      that a detector coupled with 1 mm thick GPA tape produced equivalent detector
      flood histograms to those from a design coupled with SiG and a 1 mm thick glass
      lightguide. No significant degradation in photopeak amplitude and energy
      resolution was observed over five months of measurements, indicating the tapes
      maintain their coupling integrity over several months. Though minimal photopeak
      amplitude degradation compared to SiG occurs, double-sided tapes are convenient
      alternatives for optical coupling materials since they diffuse light
      intrinsically, acting as a light guide, offer mechanical support and durability,
      are easily applied and removed from scintillators/photodetectors, and are
      relatively inexpensive and readily available.

PMID- 29337300
TI  - Hydrodynamic shrinkage of liquid CO<sub>2</sub> Taylor drops in a straight
      microchannel.
AB  - Hydrodynamic shrinkage of liquid CO2 drops in water under a Taylor flow regime is
      studied using a straight microchannel (length/width ~ 100). A general form of a
      mathematical model of the solvent-side mass transfer coefficient (ks) is
      developed first. Based on formulations of the surface area (A) and the volume (V)
      of a general Taylor drop in a rectangular microchannel, a specific form of ks is
      derived. Drop length and speed are experimentally measured at three specified
      positions of the straight channel, namely, immediately after drop generation
      (position 1), the midpoint of the channel (position 2) and the end of the channel
      (position 3). The reductions of drop length (Lx, x = 1, 2, 3) from position 1 to
      2 and down to 3 are used to quantify the drop shrinkage. Using the specific
      model, ks is calculated mainly based on Lx and drop flowing time (t). Results
      show that smaller CO2 drops produced by lower flow rate ratios (QLCO2/QH2O) are
      generally characterized by higher (nearly three times) ks and Sherwood numbers
      than those produced by higher QLCO2/QH2O, which is essentially attributed to the
      larger effective portion of the smaller drop contributing in the mass transfer
      under same levels of the flowing time and the surface-to-volume ratio (~ 104 m-1)
      of all drops. Based on calculated pressure drops of the segmented flow in
      microchannel, the Peng-Robinson equation of state (EOS) and initial pressures of
      drops at the T-junction in experiments, overall pressure drop (DeltaPt) in the
      straight channel as well as the resulted drop volume change are quantified.
      DeltaPt from position 1 to 3 is by average 3.175 kPa with a ~1.6% standard error,
      which only leads to relative drop volume changes of 0.30/00 to 0.520/00.

PMID- 29337301
TI  - Hepatic Gi signaling regulates whole-body glucose homeostasis.
AB  - An increase in hepatic glucose production (HGP) is a key feature of type 2
      diabetes. Excessive signaling through hepatic Gs-linked glucagon receptors
      critically contributes to pathologically elevated HGP. Here, we tested the
      hypothesis that this metabolic impairment can be counteracted by enhancing
      hepatic Gi signaling. Specifically, we used a chemogenetic approach to
      selectively activate Gi-type G proteins in mouse hepatocytes in vivo.
      Unexpectedly, activation of hepatic Gi signaling triggered a pronounced increase
      in HGP and severely impaired glucose homeostasis. Moreover, increased Gi
      signaling stimulated glucose release in human hepatocytes. A lack of functional
      Gi-type G proteins in hepatocytes reduced blood glucose levels and protected mice
      against the metabolic deficits caused by the consumption of a high-fat diet.
      Additionally, we delineated a signaling cascade that links hepatic Gi signaling
      to ROS production, JNK activation, and a subsequent increase in HGP. Taken
      together, our data support the concept that drugs able to block hepatic Gi
      coupled GPCRs may prove beneficial as antidiabetic drugs.

PMID- 29337302
TI  - Critical roles of alphaII spectrin in brain development and epileptic
      encephalopathy.
AB  - The nonerythrocytic alpha-spectrin-1 (SPTAN1) gene encodes the cytoskeletal
      protein alphaII spectrin. Mutations in SPTAN1 cause early infantile epileptic
      encephalopathy type 5 (EIEE5); however, the role of alphaII spectrin in
      neurodevelopment and EIEE5 pathogenesis is unknown. Prior work suggests that
      alphaII spectrin is absent in the axon initial segment (AIS) and contributes to a
      diffusion barrier in the distal axon. Here, we have shown that alphaII spectrin
      is expressed ubiquitously in rodent and human somatodendritic and axonal domains.
      CRISPR-mediated deletion of Sptan1 in embryonic rat forebrain by in utero
      electroporation caused altered dendritic and axonal development, loss of the AIS,
      and decreased inhibitory innervation. Overexpression of human EIEE5 mutant SPTAN1
      in embryonic rat forebrain and mouse hippocampal neurons led to similar
      developmental defects that were also observed in EIEE5 patient-derived neurons.
      Additionally, patient-derived neurons displayed aggregation of spectrin
      complexes. Taken together, these findings implicate alphaII spectrin in critical
      aspects of dendritic and axonal development and synaptogenesis, and support a
      dominant-negative mechanism of SPTAN1 mutations in EIEE5.

PMID- 29337303
TI  - PD-L1 on host cells is essential for PD-L1 blockade-mediated tumor regression.
AB  - Programmed death-ligand 1 (PD-L1) expression on tumor cells is essential for T
      cell impairment, and PD-L1 blockade therapy has shown unprecedented durable
      responses in several clinical studies. Although higher expression of PD-L1 on
      tumor cells is associated with a better immune response after Ab blockade, some
      PD-L1-negative patients also respond to this therapy. In the current study, we
      explored whether PD-L1 on tumor or host cells was essential for anti-PD-L1
      mediated therapy in 2 different murine tumor models. Using real-time imaging in
      whole tumor tissues, we found that anti-PD-L1 Ab accumulates in tumor tissues,
      regardless of the status of PD-L1 expression on tumor cells. We further observed
      that, while PD-L1 on tumor cells was largely dispensable for the response to
      checkpoint blockade, PD-L1 in host myeloid cells was essential for this response.
      Additionally, PD-L1 signaling in defined antigen-presenting cells (APCs)
      negatively regulated and inhibited T cell activation. PD-L1 blockade inside
      tumors was not sufficient to mediate regression, as limiting T cell trafficking
      reduced the efficacy of the blockade. Together, these findings demonstrate that
      PD-L1 expressed in APCs, rather than on tumor cells, plays an essential role in
      checkpoint blockade therapy, providing an insight into the mechanisms of this
      therapy.

PMID- 29337304
TI  - The host protecting the tumor from the host - targeting PD-L1 expressed by host
      cells.
AB  - Tumors frequently escape from immune surveillance by hijacking the natural
      control mechanisms that regulate normal immune responses. The programmed death-1
      receptor (PD-1) on T cells normally helps limit excessive immune activation, but
      it can also suppress beneficial antitumor immunity. In the clinic, blocking
      either PD-1 or one of its principal counterligands, programmed death-ligand 1 (PD
      L1), can lead to dramatic responses in certain patients. Because PD-L1 can be
      expressed by both the tumor cells themselves and also the host cells, including
      host immune cells, the actual mechanistic target of therapy has remained unclear.
      In the current issue of the JCI, two papers, one by Tang and colleagues and the
      other by Lin and colleagues, used a variety of mouse tumor models to demonstrate
      that the relevant target for therapy in each case was the PD-L1 molecules
      expressed by host cells and not by tumor cells. If this finding is generalized to
      humans, then it would suggest that the tumor persuades the host to actively
      suppress its own attempted immune response against the tumor cells.

PMID- 29337305
TI  - Host expression of PD-L1 determines efficacy of PD-L1 pathway blockade-mediated
      tumor regression.
AB  - Programmed death-1 receptor (PD-L1, B7-H1) and programmed cell death protein 1
      (PD-1) pathway blockade is a promising therapy for treating cancer. However, the
      mechanistic contribution of host and tumor PD-L1 and PD-1 signaling to the
      therapeutic efficacy of PD-L1 and PD-1 blockade remains elusive. Here, we
      evaluated 3 tumor-bearing mouse models that differ in their sensitivity to PD-L1
      blockade and demonstrated a loss of therapeutic efficacy of PD-L1 blockade in
      immunodeficient mice and in PD-L1- and PD-1-deficient mice. In contrast, neither
      knockout nor overexpression of PD-L1 in tumor cells had an effect on PD-L1
      blockade efficacy. Human and murine studies showed high levels of functional PD
      L1 expression in dendritic cells and macrophages in the tumor microenvironments
      and draining lymph nodes. Additionally, expression of PD-L1 on dendritic cells
      and macrophages in ovarian cancer and melanoma patients correlated with the
      efficacy of treatment with either anti-PD-1 alone or in combination with anti
      CTLA-4. Thus, PD-L1-expressing dendritic cells and macrophages may
      mechanistically shape and therapeutically predict clinical efficacy of PD-L1/PD-1
      blockade.

PMID- 29337306
TI  - Zinc transporter Slc39a8 is essential for cardiac ventricular compaction.
AB  - Isolated left ventricular noncompaction (LVNC) results from excessive
      trabeculation and impaired myocardial compaction during heart development. The
      extracellular matrix (ECM) that separates endocardium from myocardium plays a
      critical but poorly understood role in ventricular trabeculation and compaction.
      In an attempt to characterize solute carrier family 39 member 8-null (Slc39a8
      null) mice, we discovered that homozygous null embryos do not survive
      embryogenesis and exhibit a cardiac phenotype similar to human LVNC. Slc39a8
      encodes a divalent metal cation importer that has been implicated in ECM
      degradation through the zinc/metal regulatory transcription factor 1 (Zn/MTF1)
      axis, which promotes the expression of ECM-degrading enzymes, including Adamts
      metalloproteinases. Here, we have shown that Slc39a8 is expressed by endothelial
      cells in the developing mouse heart, where it serves to maintain cellular Zn
      levels. Furthermore, Slc39a8-null hearts exhibited marked ECM accumulation and
      reduction of several Adamts metalloproteinases. Consistent with the in vivo
      observations, knockdown of SLC39A8 in HUVECs decreased ADAMTS1 transcription by
      decreasing cellular Zn uptake and, as a result, MTF1 transcriptional activity.
      Our study thus identifies a gene underlying ventricular trabeculation and
      compaction development, and a pathway regulating ECM during myocardial
      morphogenesis.

PMID- 29337307
TI  - A double negative: inhibition of hepatic Gi signaling improves glucose
      homeostasis.
AB  - Hepatic glucose production (HGP) is a key determinant of glucose homeostasis.
      Glucagon binding to its cognate seven-transmembrane Gs-coupled receptor in
      hepatocytes stimulates cAMP production, resulting in increased HGP. In this issue
      of the JCI, Rossi and colleagues tested the hypothesis that activation of hepatic
      Gi-coupled receptors, which should inhibit cAMP production, would oppose the cAMP
      inducing action of glucagon and thereby decrease HGP. Surprisingly, however, the
      opposite occurred: activation of Gi signaling increased HGP via a novel
      mechanism, while inhibition of Gi signaling reduced HGP. These results define a
      new physiologic role for hepatic Gi signaling and identify a potential
      therapeutic target for HGP regulation.

PMID- 29337308
TI  - RAGE binds preamyloid IAPP intermediates and mediates pancreatic beta cell
      proteotoxicity.
AB  - Islet amyloidosis is characterized by the aberrant accumulation of islet amyloid
      polypeptide (IAPP) in pancreatic islets, resulting in beta cell toxicity, which
      exacerbates type 2 diabetes and islet transplant failure. It is not fully clear
      how IAPP induces cellular stress or how IAPP-induced toxicity can be prevented or
      treated. We recently defined the properties of toxic IAPP species. Here, we have
      identified a receptor-mediated mechanism of islet amyloidosis-induced
      proteotoxicity. In human diabetic pancreas and in cellular and mouse models of
      islet amyloidosis, increased expression of the receptor for advanced glycation
      endproducts (RAGE) correlated with human IAPP-induced (h-IAPP-induced) beta cell
      and islet inflammation, toxicity, and apoptosis. RAGE selectively bound toxic
      intermediates, but not nontoxic forms of h-IAPP, including amyloid fibrils. The
      isolated extracellular ligand-binding domains of soluble RAGE (sRAGE) blocked
      both h-IAPP toxicity and amyloid formation. Inhibition of the interaction between
      h-IAPP and RAGE by sRAGE, RAGE-blocking antibodies, or genetic RAGE deletion
      protected pancreatic islets, beta cells, and smooth muscle cells from h-IAPP
      induced inflammation and metabolic dysfunction. sRAGE-treated h-IAPP Tg mice were
      protected from amyloid deposition, loss of beta cell area, beta cell
      inflammation, stress, apoptosis, and glucose intolerance. These findings
      establish RAGE as a mediator of IAPP-induced toxicity and suggest that targeting
      the IAPP/RAGE axis is a potential strategy to mitigate this source of beta cell
      dysfunction in metabolic disease.

PMID- 29337309
TI  - Role for VGLUT2 in selective vulnerability of midbrain dopamine neurons.
AB  - Parkinson's disease is characterized by the loss of dopamine (DA) neurons in the
      substantia nigra pars compacta (SNc). DA neurons in the ventral tegmental area
      are more resistant to this degeneration than those in the SNc, though the
      mechanisms for selective resistance or vulnerability remain poorly understood. A
      key to elucidating these processes may lie within the subset of DA neurons that
      corelease glutamate and express the vesicular glutamate transporter VGLUT2. Here,
      we addressed the potential relationship between VGLUT expression and DA neuronal
      vulnerability by overexpressing VGLUT in DA neurons of flies and mice. In
      Drosophila, VGLUT overexpression led to loss of select DA neuron populations.
      Similarly, expression of VGLUT2 specifically in murine SNc DA neurons led to
      neuronal loss and Parkinsonian behaviors. Other neuronal cell types showed no
      such sensitivity, suggesting that DA neurons are distinctively vulnerable to
      VGLUT2 expression. Additionally, most DA neurons expressed VGLUT2 during
      development, and coexpression of VGLUT2 with DA markers increased following
      injury in the adult. Finally, conditional deletion of VGLUT2 made DA neurons more
      susceptible to Parkinsonian neurotoxins. These data suggest that the balance of
      VGLUT2 expression is a crucial determinant of DA neuron survival. Ultimately,
      manipulation of this VGLUT2-dependent process may represent an avenue for
      therapeutic development.

PMID- 29337310
TI  - OATP1B2 deficiency protects against paclitaxel-induced neurotoxicity.
AB  - Paclitaxel is among the most widely used anticancer drugs and is known to cause a
      dose-limiting peripheral neurotoxicity, the initiating mechanisms of which remain
      unknown. Here, we identified the murine solute carrier organic anion-transporting
      polypeptide B2 (OATP1B2) as a mediator of paclitaxel-induced neurotoxicity.
      Additionally, using established tests to assess acute and chronic paclitaxel
      induced neurotoxicity, we found that genetic or pharmacologic knockout of OATP1B2
      protected mice from mechanically induced allodynia, thermal hyperalgesia, and
      changes in digital maximal action potential amplitudes. The function of this
      transport system was inhibited by the tyrosine kinase inhibitor nilotinib through
      a noncompetitive mechanism, without compromising the anticancer properties of
      paclitaxel. Collectively, our findings reveal a pathway that explains the
      fundamental basis of paclitaxel-induced neurotoxicity, with potential
      implications for its therapeutic management.

PMID- 29337312
TI  - China CO2 emission accounts 1997-2015.
AB  - China is the world's top energy consumer and CO2 emitter, accounting for 30% of
      global emissions. Compiling an accurate accounting of China's CO2 emissions is
      the first step in implementing reduction policies. However, no annual, officially
      published emissions data exist for China. The current emissions estimated by
      academic institutes and scholars exhibit great discrepancies. The gap between the
      different emissions estimates is approximately equal to the total emissions of
      the Russian Federation (the 4th highest emitter globally) in 2011. In this study,
      we constructed the time-series of CO2 emission inventories for China and its 30
      provinces. We followed the Intergovernmental Panel on Climate Change (IPCC)
      emissions accounting method with a territorial administrative scope. The
      inventories include energy-related emissions (17 fossil fuels in 47 sectors) and
      process-related emissions (cement production). The first version of our dataset
      presents emission inventories from 1997 to 2015. We will update the dataset
      annually. The uniformly formatted emission inventories provide data support for
      further emission-related research as well as emissions reduction policy-making in
      China.

PMID- 29337311
TI  - Dinaciclib induces immunogenic cell death and enhances anti-PD1-mediated tumor
      suppression.
AB  - Blockade of the checkpoint inhibitor programmed death 1 (PD1) has demonstrated
      remarkable success in the clinic for the treatment of cancer; however, a majority
      of tumors are resistant to anti-PD1 monotherapy. Numerous ongoing clinical
      combination therapy studies will likely reveal additional therapeutics that
      complement anti-PD1 blockade. Recent studies found that immunogenic cell death
      (ICD) improves T cell responses against different tumors, thus indicating that
      ICD may further augment antitumor immunity elicited by anti-PD1. Here, we
      observed antitumor activity following combinatorial therapy with anti-PD1 Ab and
      the cyclin-dependent kinase inhibitor dinaciclib in immunocompetent mouse tumor
      models. Dinaciclib induced a type I IFN gene signature within the tumor, leading
      us to hypothesize that dinaciclib potentiates the effects of anti-PD1 by
      eliciting ICD. Indeed, tumor cells treated with dinaciclib showed the hallmarks
      of ICD including surface calreticulin expression and release of high mobility
      group box 1 (HMGB1) and ATP. Mice treated with both anti-PD1 and dinaciclib
      showed increased T cell infiltration and DC activation within the tumor,
      indicating that this combination improves the overall quality of the immune
      response generated. These findings identify a potential mechanism for the
      observed benefit of combining dinaciclib and anti-PD1, in which dinaciclib
      induces ICD, thereby converting the tumor cell into an endogenous vaccine and
      boosting the effects of anti-PD1.

PMID- 29337313
TI  - Complete genome sequencing of the luminescent bacterium, Vibrio qinghaiensis sp.
      Q67 using PacBio technology.
AB  - Vibrio qinghaiensis sp.-Q67 (Vqin-Q67) is a freshwater luminescent bacterium that
      continuously emits blue-green light (485 nm). The bacterium has been widely used
      for detecting toxic contaminants. Here, we report the complete genome sequence of
      Vqin-Q67, obtained using third-generation PacBio sequencing technology.
      Continuous long reads were attained from three PacBio sequencing runs and reads
      >500 bp with a quality value of >0.75 were merged together into a single dataset.
      This resultant highly-contiguous de novo assembly has no genome gaps, and
      comprises two chromosomes with substantial genetic information, including protein
      coding genes, non-coding RNA, transposon and gene islands. Our dataset can be
      useful as a comparative genome for evolution and speciation studies, as well as
      for the analysis of protein-coding gene families, the pathogenicity of different
      Vibrio species in fish, the evolution of non-coding RNA and transposon, and the
      regulation of gene expression in relation to the bioluminescence of Vqin-Q67.

PMID- 29337315
TI  - Correction: One-step coelectrodeposition-assisted layer-by-layer assembly of gold
      nanoparticles and reduced graphene oxide and its self-healing three-dimensional
      nanohybrid for an ultrasensitive DNA sensor.
AB  - Correction for 'One-step coelectrodeposition-assisted layer-by-layer assembly of
      gold nanoparticles and reduced graphene oxide and its self-healing three
      dimensional nanohybrid for an ultrasensitive DNA sensor' by Jayakumar Kumarasamy,
      et al., Nanoscale, 2018, DOI: 10.1039/c7nr06952a.

PMID- 29337314
TI  - The reconstruction of 2,631 draft metagenome-assembled genomes from the global
      oceans.
AB  - Microorganisms play a crucial role in mediating global biogeochemical cycles in
      the marine environment. By reconstructing the genomes of environmental organisms
      through metagenomics, researchers are able to study the metabolic potential of
      Bacteria and Archaea that are resistant to isolation in the laboratory. Utilizing
      the large metagenomic dataset generated from 234 samples collected during the
      Tara Oceans circumnavigation expedition, we were able to assemble 102 billion
      paired-end reads into 562 million contigs, which in turn were co-assembled and
      consolidated in to 7.2 million contigs >=2 kb in length. Approximately 1 million
      of these contigs were binned to reconstruct draft genomes. In total, 2,631 draft
      genomes with an estimated completion of >=50% were generated (1,491 draft genomes
      >70% complete; 603 genomes >90% complete). A majority of the draft genomes were
      manually assigned phylogeny based on sets of concatenated phylogenetic marker
      genes and/or 16S rRNA gene sequences. The draft genomes are now publically
      available for the research community at-large.

PMID- 29337316
TI  - Enhanced selectivity for Mg2+ with a phosphinate-based chelate: APDAP versus
      APTRA.
AB  - o-Aminophenol-N,N,O-triacetate, known as APTRA, is one of the most well
      established ligands for targeting magnesium ions but, like other aminocarboxylate
      ligands, it binds Ca2+ much more strongly than Mg2+. The synthesis of an O
      phosphinate analogue of APTRA is reported here, namely o-aminophenol-N,N
      diacetate-O-methylene-methylphosphinate, referred to as APDAP. Metal binding
      studies monitored using UV-visible spectroscopy show that the affinity of APDAP
      for Ca2+ is reduced by over two orders of magnitude compared to APTRA, and for
      Zn2+ by over three orders of magnitude, whereas the affinity for Mg2+ is
      attenuated to a much lesser extent, by a factor of only about 7. The selectivity
      towards Mg2+ is thus substantially improved. DFT calculations support the notion
      that longer P-O and P-C bonds in APDAP (compared to corresponding C-O and C-C
      bonds in APTRA) favour a larger angle at the metal, an effect that is less
      unfavourable for smaller ions like Mg2+ than for larger ions such as Ca2+.
      Derivatives of APDAP can be anticipated that will offer improved sensing of Mg2+
      in the presence of Ca2+, in the physiologically important millimolar
      concentration range.

PMID- 29337317
TI  - Correction: Nucleobases, nucleosides, and nucleotides: versatile biomolecules for
      generating functional nanomaterials.
AB  - Correction for 'Nucleobases, nucleosides, and nucleotides: versatile biomolecules
      for generating functional nanomaterials' by Fang Pu et al., Chem. Soc. Rev.,
      2018, DOI: .

PMID- 29337318
TI  - HOMEs for plants and microbes - a phenotyping approach with quantitative control
      of signaling between organisms and their individual environments.
AB  - We describe a simple, scalable, modular, and frugal approach to create model
      ecosystems as millifluidic networks of interconnected habitats (hosting microbes
      or plants), which offers (i) quantitative and dynamic control over the exchange
      of chemicals between habitats, and (ii) independent control over their
      environment. Oscillatory laminar flows produce regions of vortex mixing around
      obstacles. When these overlap, rapid mass transport by dispersion occurs, which
      is quantitatively describable as diffusion, but is directional and tunable in
      rate over 3 orders of magnitude. This acceleration in the rate of diffusion is
      equivalent to reducing the distance between the habitats, and therefore, the
      organisms, down to the length scales characteristic of signaling in soil (<2 mm).

PMID- 29337319
TI  - The effects of interaction between particulate matter and temperature on
      mortality in Beijing, China.
AB  - BACKGROUND: the effects of interaction between temperature and inhalable
      particulate matter (aerodynamic diameter < 10 MUm, PM10) on mortality have been
      examined in some previous studies, but the results were inconsistent. This study
      aims to explore whether the effects of PM10 on daily non-accidental,
      cardiovascular and respiratory mortality were modified by temperature levels in
      Beijing from 2006 to 2009. METHODS: we applied a bivariate response surface model
      and temperature-stratified model based on time-series Poisson generalized
      additive models (GAMs) to examine the interactive effects in single- and two
      pollutant models. The modification of age and gender was examined in subgroup
      analyses. RESULTS: the median of temperature (15.9  degrees C) and visualized
      turning point (20  degrees C) were chosen as cut-offs to define the temperature
      strata as two levels (low and high). Results showed that the effect estimates of
      PM10 were stronger at the high temperature level for non-accidental,
      cardiovascular and respiratory mortality than at the low temperature level. When
      controlling the moving average lag of temperature for 14 days, the effect
      estimates per 10 MUg m-3 increase in PM10 for non-accidental, cardiovascular and
      respiratory mortality increased 0.14% (95% CI: 0.05, 0.22), 0.12% (95% CI: 0.02,
      0.23) and 0.14% (95% CI: -0.06, 0.34) when the temperature was low and 0.24% (95%
      CI: 0.12, 0.35), 0.17% (95% CI: 0.01, 0.34) and 0.45% (95% CI: 0.13, 0.78) at the
      high temperature level, respectively. In the two-pollutant model, the effects of
      PM10 were attenuated at both high and low temperatures at all lags after
      adjusting SO2 and NO2. The PM10 effects were stronger at the high temperature
      level for females and elderly people (>=65 years old). CONCLUSION: the findings
      suggest that daily mortality attributed to PM10 might be modified by temperature.
      The interaction between air pollution and global climate change has potential
      strategy and policy implications.

PMID- 29337320
TI  - Homochiral hexanuclear nickel(ii) metallocyclic structures with high activity for
      the photocatalytic degradation of organic dyes.
AB  - Enantiopure ligands, namely (R,R)- and (S,S)-2,2'-(1,4-phenylene) bis(4,5
      dihydrothiazole-4-carboxylic acid) (H2LRR, and H2LSS) were synthesized, and
      homochiral metallocyclic rings {Ni6LRR6(H2O)12} (1RR) and {Ni6LSS6(H2O)12} (1SS)
      were obtained and their structures were determined. The complexes exhibit
      excellent activity for the photocatalytic degradation of organic dyes.

PMID- 29337322
TI  - Structural revision of two unusual rhamnofolane diterpenes, curcusones I and J,
      by means of DFT calculations of NMR shifts and coupling constants.
AB  - The stereochemical revision of two recently reported rhamnofolane diterpenes,
      curcusones I and J, was enabled by quantum calculations of NMR shifts and
      coupling constants at DFT levels. DP4+ results and reexamination of the NMR data
      suggest that curcusones I and J should be revised as CS32 and CS28, respectively.

PMID- 29337321
TI  - Synthesis, spectroscopic investigation, and DFT study of N,N'-disubstituted
      ferrocene-based thiourea complexes as potent anticancer agents.
AB  - In the present work, the synthesis, characterization (FT-IR, multinuclear (1H and
      13C) NMR, AAS, Raman, and elemental analyses), DNA binding (cyclic voltammetry,
      UV-Vis spectroscopy), and in vitro biological screening of nine new ferrocene
      incorporated thioureas (A1-A9) are reported. Furthermore, the single-crystal X
      ray structure of compound A8 was also determined. The ferrocene-based N,N'
      disubstituted thioureas were derived by allowing the ferrocenyl anilines to react
      with freshly prepared isothiocyanates under a N2 atmosphere in dry acetone. The
      DNA binding studies performed by cyclic voltammetry and UV-Vis spectroscopy
      produced results that are in close agreement with one another for the binding
      constants (K) and an electrostatic mode of interaction was observed. The
      DFT/B3LYP method was used to determine the charge distribution and HOMO/LUMO
      energies of the optimized structure. The DFT calculated HOMO and LUMO energies
      correlate well with the experimentally determined redox potential values. The
      synthesized ferrocenyl thioureas exhibited good scavenging activity against the
      1,1-diphenyl-2-picrylhydrazyl radical (DPPH). These complexes were also scanned
      for their in vitro cytotoxic activity against MCF-7 carcinoma cells, and also
      towards the non-cancerous cell line MCF-10A. The results showed modest
      cytotoxicity against the subjected cancer cell line compared with a standard
      chemotherapeutic drug (cisplatin). However, these ferrocenyl derivatives have
      fewer toxic effects in normal cells.

PMID- 29337323
TI  - Conversion of CO2 into cyclic carbonates by a Co(ii) metal-organic framework and
      the improvement of catalytic activity via nanocrystallization.
AB  - The Co(ii) metal-organic framework (MOF) {[Co(MU3-L)(H2O)].0.5H2O}n (1, H2L =
      thiazolidine 2,4-dicarboxylic acid) with rich Lewis acid sites was used as a
      catalyst for the conversion of CO2 and propylene oxide into propylene carbonate
      with a yield of up to 98% under 50  degrees C and 1 atm. 1 exhibited excellent
      reusability, which could be regenerated easily for at least five runs without a
      decrease in the yield. Importantly, we synthesized two types of nano-crystals (N1
      and N2) of 1 with polyvinylpyrrolidone (PVP) and hexadecyltrimethylammonium
      bromide (CTAB) as surfactants, respectively, and investigated their catalytic
      properties in comparison with that of 1 in the powder phase. A significant
      enhancement in both catalytic efficiency and product yield was observed when 1
      was nano-crystallized. This is the first investigation about the relationship
      between the morphology and the catalytic parameters of MOFs. The results showed a
      strategy for efficiently applying MOFs as catalysts towards CO2 conversion, which
      could also be used in other MOF-catalyzed processes.

PMID- 29337324
TI  - Polymerization kinetics of a multi-functional silica precursor studied using a
      novel Monte Carlo simulation technique.
AB  - Silica polymerization has been extensively used to synthesize various fascinating
      materials for industrial and technological applications. The polymerization
      protocol is modified by altering several parameters (such as the concentration of
      the precursor, temperature, pH) heuristically to obtain the desired end product.
      To properly understand the effect of such parameters, knowledge of molecular
      events occurring during the process of polymerization is essential. In this work,
      we developed algorithms to capture molecular events such as translation,
      rotation, and reactions using the reaction ensemble Monte Carlo (REMC) technique.
      Our algorithms simulate molecular events in accordance with physical time by
      correctly scaling the movements of a cluster with the monomer, thereby capturing
      the kinetics of the process. We studied the polymerization of the four
      coordinated silica (f4) precursor using our algorithm and observed excellent
      agreement between simulation results and experimental data. The algorithm was
      also used to study the polymerization of the three coordinated silica (f3)
      precursor and it was found that our simulations capture experimental kinetics
      well, thereby confirming that the developed algorithms are robust. We studied the
      effect of the functionality of the precursor on polymerization kinetics and the
      resulting structure by simulating silica systems having a mixture of two, three
      and four functional (f2, f3, and f4) silica precursors. We observed that network
      formation and cluster size decrease with the increase in the concentration of the
      f2 precursor. The radius of gyration (Rg) of the system initially increases due
      to network formation and decreases later due to the collapse of a large cluster.
      The Rg is directly correlated with the total number of primitive rings present in
      the system. The molecular level understanding obtained will be useful in the
      design of tailored silica nanoparticles.

PMID- 29337325
TI  - Design of donor-acceptor copolymers for organic photovoltaic materials: a
      computational study.
AB  - 80 different push-pull type organic chromophores which possess Donor-Acceptor (D
      A) and Donor-Thiophene-Acceptor-Thiophene (D-T-A-T) structures have been
      systematically investigated by means of density functional theory (DFT) and time
      dependent DFT (TD-DFT) at the B3LYP/6-311G* level. The introduction of thiophene
      (T) in the chain has allowed us to monitor the effect of pi-spacers. Benchmark
      studies on the methodology have been carried out to predict the HOMO and LUMO
      energies and optical band gaps of the D-A systems accurately. The HOMO and LUMO
      energies and transition dipoles are seen to converge for tetrameric oligomers,
      and the latter have been used as optimal chain length to evaluate various
      geometrical and optoelectronic properties such as bond length alternations,
      distortion energies, frontier molecular orbital energies, reorganization energies
      and excited-state vertical transition of the oligomers. Careful analysis of our
      findings has allowed us to propose potential donor-acceptor couples to be used in
      organic photovoltaic cells.

PMID- 29337326
TI  - Synthesis, characterization and derivatization of hydroxyl-functionalized
      iron(ii) bis(NHC) complexes.
AB  - The syntheses of a novel hydroxyl-functionalized tetradentate NHC/pyridine hybrid
      ligand and the corresponding Ag(i) and Fe(ii) complexes are presented.
      Spectroscopic and X-ray diffraction techniques are used for structural
      investigations and cyclic voltammetry measurements reveal interesting electronic
      properties. Transmetalation of the trinuclear Ag(i) complex (C1) yields a
      mononuclear and a dinuclear iron(ii) bis(NHC) complex (C2 and C3), which can be
      separated by stepwise precipitation. The former is isostructural to iron(ii)
      bis(NHC) complex A, which is a versatile oxidation catalyst. Furthermore,
      suitable conditions for esterification reactions of the ligand precursor and
      iron(ii) bis(NHC) complex (C2) have been established, demonstrating the utility
      of the hydroxyl functionality for immobilization and derivatization purposes.

PMID- 29337327
TI  - Modulating inflammation in a cutaneous chronic wound model by IL-10 released from
      collagen-silica nanocomposites via gene delivery.
AB  - Cutaneous chronic wounds remain a major clinical challenge which requires the
      development of novel wound dressings. Previously, we showed that collagen-silica
      nanocomposites consisting of polyethyleneimine (PEI)-DNA complexes associated
      with silica nanoparticles (SiNP), collagen hydrogel and 3T3 fibroblasts, can work
      as a local "cell factory". Indeed, the "in-gel" transfection leads to a sustained
      production and release of biomolecules. Herein, we further explored the
      possibility for nanocomposites to deliver interleukin-10 (IL-10), a potent anti
      inflammatory cytokine, which favors tissue repair. Its anti-inflammatory effect
      was evaluated in an in vitro inflammation model carried out by LPS
      (lipopolysaccharide) activation of macrophages embedded in collagen gel. The IL
      10 synthesis from nanocomposites was detected over one week in the range of 200
      400 pg mL-1 and reached a maximum at day 5 without any observed cytotoxic
      effects. PEI10-SiNP outperformed free PEI10 and PEI25-SiNP, implying that the
      introduction of SiNP improved the transfection efficiency of low Mw of PEI. In
      addition, the structure and mechanical properties of collagen-silica
      nanocomposites were stable over one week. Subsequently, the ability of
      nanocomposites to modulate inflammation was tested in a 3D model of inflammation.
      The decrease of TNF-alpha and IL-1beta gene expression by 20-80% indicated
      successful inhibition of inflammation by IL-10 released from nanocomposites.
      Taken together, the nanocomposites are capable of producing effective doses of IL
      10 which inhibit the synthesis of pro-inflammatory cytokines and favor the
      expression of wound healing cytokines. Therefore, the as-constructed 3D gene
      delivery system represents a promising strategy for the controlled release of
      therapeutic biomolecules favoring cutaneous wound healing.

PMID- 29337328
TI  - Self-assembly of high-index faceted gold nanocrystals to fabricate tunable
      coupled plasmonic superlattices.
AB  - Herein, we present an effective bottom-up strategy to fabricate unprecedented
      macroscopic two-dimensional (2D) plasmonic gold superlattices composed of high
      index faceted gold nanocrystal building blocks (NBBs) at the air-liquid
      interface. In this approach, a synergistic electrostatic and layered self
      assembly technique was executed using unique icosidodecahedral gold nanocrystals.
      It showed that centimeter-squared areas of close-packed monolayer films were
      formed, and the interparticle spacing of neighbouring Au NBBs could be facilely
      manipulated from hundreds to several nanometers. Optical characterization
      demonstrated that particular plasmonic coupling could occur and enhance in a wide
      spectral range (visible and near-IR) as the self-assembled Au superlattices were
      tuned for an appropriate gap distance and specific NBB size; however, the
      orientation of individual NBBs remained somewhat unorganized. Thus, the well
      pronounced shift of localized surface plasmon resonances (LSPR) and the in-depth
      resonance splitting behaviors were presented in our investigations. Furthermore,
      corresponding electromagnetic simulations showed good agreement with the
      experimental results; this indicated that a new class of tunable coupled
      plasmonic Au superlattices was realized. This study complements the insights into
      the plasmonic coupling of layered Au superlattices and enables the colloidal self
      assembly to extend to unconventional NBBs; thus, it may facilitate the design of
      novel plasmonic metamaterials or other superstructures for desired
      functionalities and applications in the future.

PMID- 29337330
TI  - ?

PMID- 29337329
TI  - Ultra-low-temperature growth of CdS quantum dots on g-C3N4 nanosheets and their
      photocatalytic performance.
AB  - CdS quantum dots deposited on carbon nitride (g-C3N4) nanosheets have been
      synthesized by ultra-low temperature (-60  degrees C) liquid phase precipitation
      reactions. The obtained CdS quantum dots were uniformly distributed on the
      surface of the g-C3N4 nanosheets with an average diameter of 5 nm.
      Correspondingly, CdS/g-C3N4 exhibits a highly enhanced photocatalytic
      performance.

PMID- 29337331
TI  - ?

PMID- 29337333
TI  - ?

PMID- 29337332
TI  - ?

PMID- 29337334
TI  - ?

PMID- 29337335
TI  - ?

PMID- 29337336
TI  - ?

PMID- 29337337
TI  - ?
AB  - Automatic infectious disease consultant alert is associated with decreased
      mortality and readmission rate in Staphylococcus aureus bacteriemia A management
      plan was implemented at a 2000 bed teaching hospital where positive blood
      cultures with growth of Staphylococcus aureus were reported simultaneously to the
      ordering unit and to the Infectious Disease Consultant. Readmission rate and 30
      day mortality were compared one year before and one year after introduction of
      the management plan. Out of totally 320 respectively 321 patients with SAB 252
      and 244 were included in the study. 30-day mortality decreased from 26/252 (10%)
      to 14/244 (5,7%) (p=0.059) when all patients with SAB were included and to 9/193
      (4,7%) (p=0,026) when only patients who received a formal consultation after
      introduction of the management plan were included. The rate of readmission within
      30 days declined from 38/227 (17%) in 2014-2015 to 24/230 (10%) in 2015-2016
      (p=0,049).

PMID- 29337338
TI  - ?
AB  - Good outcomes when emergency physicians diagnosed deep vein thrombosis Deep vein
      thrombosis of the lower limb is best diagnosed with ultrasound. Internationally,
      several studies have shown promising and often equal results when emergency
      physicians have been compared with radiologists in diagnosing thrombosis. Our
      results confirm these findings in a non-academic hospital and for the first time
      in a Swedish setting. Our findings form the basis for a multi-centre study on new
      diagnostic routines in patients with suspected proximal deep vein thrombosis in
      the emergency department, potentially resulting in faster and more resource
      effective management.

PMID- 29337339
TI  - ?
AB  - Risk of optic nerve injury after prolonged Trendelenburg's position Postoperative
      loss of vision due to acute ischaemic optic nerve injury is a rare complication
      following pelvic surgery. A steep Trendelenburg's position of the patient, high
      intraabdominal pressure and a long operative time in Trendelenburg's position are
      recognised risk factors associated with robot-assisted pelvic surgery. This
      manuscript presents the underlying pathophysiologic mechanism. Practical tips and
      tricks for prevention are discussed.

PMID- 29337340
TI  - ?

PMID- 29337341
TI  - ?
AB  - MMR vaccination in 6-9 month olds Vaccination against measles using the MMR
      vaccine is licensed from 9 months of age, but is used off-label from 6 months of
      age during or when travelling to areas with an ongoing measles outbreak. In this
      review of the published literature, studies on MMR vaccination in this age group
      are limited and small in size. Immunogenicity studies indicate that infants under
      9 months respond with lower antibody titres but comparable T cell responses
      against measles. The safety profile of the vaccine does not appear to differ
      between infants vaccinated earlier or later. Vaccination from 6 months of age
      should be recommended if the risk of being infected with measles is considered
      greater than the risk of not attaining full vaccination protection.

PMID- 29337342
TI  - Polysaccharides Reduce Absorption and Mutagenicity of 3-Amino-1,4-Dimethyl-5H
      Pyrido[4,3-b]Indole In Vitro and In Vivo.
AB  - : 3-Amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) is a group 2B carcinogen
      characterized by the International Agency for Research on Cancer (IARC) and great
      efforts have been taken to reduce Trp-P-1 mutagenicity to humans. In this study,
      the effect of a reduction of Trp-P-1 on intestinal absorption as a promising
      strategy was investigated. The data showed that when 20 mM Trp-P-1 cotransported
      with 10 mM of sodium carboxymethyl cellulose (CMC), xanthan gum, or carrageenan,
      the absorption rate of Trp-P-1 was reduced by 31.5%, 49.5%, or 72.9% in MDCK-MDR1
      cell monolayer, respectively; and 64.6%, 83.4%, or 64.1% in rat intestinal
      tissues, correspondingly. These 3 polysaccharides also reduced pharmacokinetic
      parameters, that is, Cmax , AUC0-t , and AUC0-infinity , after Trp-P-1 was given
      to rats intragastrically. However, gum arabic did not exhibit similar effects on
      Trp-P-1 absorption in vitro or in vivo. The Ames test showed that these 3
      polysaccharides reduced Trp-P-1 mutagenicity to Salmonella typhimurium TA98, but
      gum arabic did not. Isothermal titration calorimetry assay indicated that Trp-P-1
      interacted with these 3 polysaccharides. Thermodynamic study showed that the
      actual value of ?H <0, but its absolute value greater than the corresponding
      value of T?S, suggest a specific interaction between Trp-P-1 and these 3
      polysaccharides, probably through the hydrogen bond and/or ion interaction.
      Reduction of Trp-P-1 intestinal absorption using food additives could be one of
      the strategies to suppress Trp-P-1-induced carcinogenesis in human. PRACTICAL
      APPLICATION: 1.This study provides insightful information for the food industry
      how gum arabic, xanthan gum, kappa carrageenan, and sodium carboxymethyl
      cellulose affect the absorption of Trp-P-1. 2.This study also provides novel
      information regarding a better formulation for meat products to reduce Trp-P-1
      absorption.

PMID- 29337343
TI  - Antimicrobial-Resistance Genetic Markers in Potentially Pathogenic Gram Positive
      Cocci Isolated from Brazilian Soft Cheese.
AB  - Although most Brazilian dairy products meet high technological standards, there
      are quality issues regarding milk production, which may reduce the final product
      quality. Several microbial species may contaminate milk during manufacture and
      handling. If antimicrobial usage remains uncontrolled in dairy cattle, the
      horizontal transfer of antimicrobial resistance genes in foodstuffs may be of
      particular concern for both food producers and dairy industry. This study focused
      on the evaluation of putative Gram positive cocci in Minas cheese and of
      antimicrobial and biocide resistance genes among the isolated bacteria.
      Representative samples of 7 different industrially trademarked Minas cheeses (n =
      35) were processed for selective culture and isolation of Gram positive cocci.
      All isolated bacteria were identified by DNA sequencing of the 16S rRNA gene.
      Antimicrobial resistance genes were screened by PCR. Overall, 208 strains were
      isolated and identified as follows: Enterococcus faecalis (47.6%), Macrococcus
      caseolyticus (18.3%), Enterococcus faecium (11.5%), Enterococcus caseliflavus
      (7.7%), Staphylococcus haemolyticus (7.2%), Staphylococcus aureus (4.3%),
      Staphylococcus epidermidis (2.9%), and Enterococcus hirae (0.5%). The genetic
      markers mecA (78.0%) and smr (71.4%) were the most prevalent, but others were
      also detected, such as blaZ (65.2%), msrA (60.9%), msrB (46.6%), linA (54.7%),
      and aacA-aphD (47.6%). The occurrence of opportunist pathogenic bacteria
      harboring antimicrobial resistance markers in the cheese samples are of special
      concern, since these bacteria are not considered harmful contaminating agents
      according to the Brazilian sanitary regulations. However, they are potentially
      pathogenic bacteria and the cheese may be considered a reservoir for
      antimicrobial resistance genes available for horizontal transfer through the food
      chain, manufacturing personnel and consumers.

PMID- 29337344
TI  - Microbiological Quality and Safety of Fresh Fruits and Vegetables at Retail
      Levels in Korea.
AB  - The aim of this study was to evaluate the microbiological quality and safety of
      fresh produce at retail level in Korea in order to periodically update
      information and establish available risks associated with consumption of fresh
      fruits and vegetables. The samples from different markets located in 3 provinces
      of South Korea were collected. The protocol in the Korean Food Standards Codex
      was applied and generic Escherichia coli, coliforms, aerobic mesophilic bacteria
      (AMB), and yeast and mold (YM) in 360 packaged and unpackaged fresh fruits and
      vegetables were analyzed. Presence of pathogens was examined using real-time
      polymerase chain reaction (q-PCR) after enrichment of samples. For all, the
      microbial counts ranged from 1.7 to 10.6 log cfu/g for AMB, 2.2 to 7.9 log cfu/g
      for coliforms, and 5.5 to 7.9 log cfu/g for YM. Three lettuce samples were
      contaminated by E. coli with a bacterial load ranging from 2 to 4 log cfu/g.
      Salmonella spp. were not detected in any fresh produce. Listeria monocytogenes,
      E. coli O157:H7, and Staphylococcus aureus were found in 1 (0.6%), 3 (0.8%), and
      5 (1.4%) fresh produce samples, respectively. Bacillus cereus (50.3%) and
      Clostridium perfringens (13.3%) had the highest prevalence. These results
      indicate the need for employing strict control measures and developing preventive
      strategies to improve the quality and safety of fresh produce in Korea.

PMID- 29337345
TI  - Sputum cytology during late-phase responses to inhalation challenge with
      different allergens.
AB  - BACKGROUND: In mouse models of allergic asthma, exposure to different allergens
      can trigger distinct inflammatory subtypes in the airways. We investigated
      whether this observation extends to humans. METHODS: We compared the frequency of
      sputum inflammatory subtypes between mild allergic asthma subjects (n = 129)
      exposed to different allergens in inhalation challenge tests. These tests were
      performed using a standardized protocol as part of clinical trials of
      experimental treatments for asthma, prior to drug randomization. Five allergen
      types were represented: the house dust mites Dermatophagoides pteronyssinus and
      Dermatophagoides farinae, ragweed, grass, and cat. RESULTS: Of 118 individuals
      with a sputum sample collected before allergen challenge (baseline), 45 (38%) had
      paucigranulocytic, 51 (43%) eosinophilic, 11 (9%) neutrophilic, and 11 (9%) mixed
      granulocytic sputum. Of note, most individuals with baseline paucigranulocytic
      sputum developed eosinophilic (48%) or mixed granulocytic (43%) sputum 7 hours
      after allergen challenge, highlighting the dynamic nature of sputum inflammatory
      subtype in asthma. Overall, there was no difference in the frequency of sputum
      inflammatory subtypes following challenge with different allergen types. Similar
      results were observed at 24 hours after allergen challenge. CONCLUSIONS: Unlike
      reported in mice, in humans the sputum inflammatory subtype observed after an
      allergen-induced asthma exacerbation is unlikely to be influenced by the type of
      allergen used.

PMID- 29337346
TI  - Effective role of medium supplementation in microalgal lipid accumulation.
AB  - The present study investigated the interaction between starch and lipid
      accumulation in a green microalgae enrichment culture. The objective was to
      optimize the lipid content by manipulation of the medium in regular batch
      culture. Two medium designs were evaluated: First a high ortho-P concentration
      with vitamin supplementary (Pi-vitamins supplemented medium), second normal
      growth medium (control). Both media contained a low amount of nitrogen which was
      consumed during batch growth in three days. The batch experiments continued for
      another 4 days with the absence of soluble nitrogen in the medium. When the mixed
      microalgal culture was incubated in the Pi-vitamin supplemented medium, the
      lipid, and starch content of the culture increased within the first 3 days to
      102.0 +/- 5.2 mg/L (12.7 +/- 0.6% of DW) and 31.7 +/- 1.6 mg/L (4.0 +/- 0.2% of
      DW), respectively. On the last day of the experiment, the lipid, and starch
      content in Pi-vitamin medium increased to 663.1 +/- 32.5 mg/L (33.4 +/- 1.6% of
      DW) and 127.5 +/- 5.2 mg/L (6.4 +/- 0.3% of DW). However, the lipid and starch
      content in the control process, reached to 334.7 +/- 16.4 mg/L (20.1 +/- 1.0% of
      DW) and 94.3 +/- 4.6 mg/L (5.7 +/- 0.3% of DW), respectively. The high Pi-vitamin
      medium induced storing lipid formation clearly while the starch formation was not
      affected. The lipid contents reported here are among the high reported in the
      literature, note that already under full growth conditions significant lipid
      levels occurred in the algal enrichment culture. The high lipid productivity of
      the reported mixed microalgae culture provides an efficient route for efficient
      algal biodiesel production.

PMID- 29337347
TI  - A latent state-trait analysis of interoceptive accuracy.
AB  - Interoceptive accuracy (IAc), that is, the ability to accurately perceive one's
      own bodily signals, is widely assumed to be a trait, although experimental
      manipulations such as stress may affect IAc. We used structural equation modeling
      to estimate the reliability of IAc, and the proportions of individual differences
      in IAc, explained by a trait and occasion-specific effects of situation and
      person-situation interactions. We assessed IAc in 59 healthy participants (40
      women, MAge  = 23.4 years) on three consecutive measurement occasions,
      approximately 1 week apart, in a rest and poststress condition, using a heartbeat
      counting and a heartbeat discrimination task. The results showed fair temporal
      stability (intraclass correlation coefficients >= 0.38) and good reliability (Mdn
      = .63; range .49-.83) for both methods. While around 40% of the variance of a
      single IAc measurement could be explained by a trait, approximately 27% was
      accounted for by occasion-specific effects of situation and person-situation
      interaction. These results suggest that IAc measures are relatively consistent
      and that situations and person-situation interactions impact IAc as measured at a
      certain point in time. An aggregation across at least two measurements is
      recommended when using IAc as a trait variable.

PMID- 29337348
TI  - Expression of the purine biosynthetic enzyme phosphoribosyl formylglycinamidine
      synthase in neurons.
AB  - Purines are metabolic building blocks essential for all living organisms on
      earth. De novo purine biosynthesis occurs in the brain and appears to play
      important roles in neural development. Phosphoribosyl formylglycinamidine
      synthase (FGAMS, also known as PFAS or FGARAT), a core enzyme involved in the de
      novo synthesis of purines, may play alternative roles in viral pathogenesis. To
      date, no thorough investigation of the endogenous expression and localization of
      de novo purine biosynthetic enzymes has been conducted in human neurons or in
      virally infected cells. In this study, we characterized expression of FGAMS using
      multiple neuronal models. In differentiated human SH-SY5Y neuroblastoma cells,
      primary rat hippocampal neurons, and in whole-mouse brain sections, FGAMS
      immunoreactivity was distributed within the neuronal cytoplasm. FGAMS
      immunolabeling in vitro demonstrated extensive distribution throughout neuronal
      processes. To investigate potential changes in FGAMS expression and localization
      following viral infection, we infected cells with the human pathogen herpes
      simplex virus 1. In infected fibroblasts, FGAMS immunolabeling shifted from a
      diffuse cytoplasmic location to a mainly perinuclear localization by 12 h post
      infection. In contrast, in infected neurons, FGAMS localization showed no
      discernable changes in the localization of FGAMS immunoreactivity. There were no
      changes in total FGAMS protein levels in either cell type. Together, these data
      provide insight into potential purine biosynthetic mechanisms utilized within
      neurons during homeostasis as well as viral infection. Cover Image for this
      Issue: doi: 10.1111/jnc.14169.

PMID- 29337349
TI  - Phytochemicals, Anti-Inflammatory, Antiproliferative, and Methylglyoxal Trapping
      Properties of Zijuan Tea.
AB  - : Zijuan tea (Camellia sinensis var. assamica) is a unique anthocyanin-rich tea
      cultivar in China. Although chemical component analysis of Zijuan tea and
      extraction technology of anthocyanins was widely documented, its functional
      properties have not been extensively explored. In this study, the anti
      inflammatory, antiproliferative, and methylglyoxal (MGO) trapping activities of
      water extract (ZWE) and ethyl acetate extract (ZEE) of Zijuan tea were
      investigated for the 1st time. Results showed that ZWE and ZEE exhibited
      inhibitory effects on nitric oxide (NO), tumor necrosis factor (TNF)-alpha, and
      interleukin (IL)-6 production as well as inducible nitric oxide synthase protein
      (iNOS) expression in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages.
      Moreover, Zijuan tea extracts exerted stronger antiproliferative activity against
      HCT-116 cells compared with HepG2 and MDA-MB-231 cells, and thus could induce
      apoptosis in HCT-116 cells in a dose-dependent manner. Furthermore, Zijuan tea
      extracts were effective in trapping MGO under simulated physiological conditions,
      and the T1/2 (the time for 50% MGO remaining) values of ZWE and ZEE were 3.69 and
      6.20 min, respectively. Additionally, the contents of total phenolics and
      catechins in ZEE were 685.43 +/- 16.00 and 454.96 +/- 4.21 mg/g extract,
      respectively, and in ZWE were 422.59 +/- 12.09 and 307.29 +/- 0.85 mg/g extract,
      respectively. Therefore, ZEE exhibited better anti-inflammatory,
      antiproliferative, and MGO trapping properties than ZWE may be mainly attributed
      to its higher (P < 0.05) content of total phenolics, expecially catechins. These
      results suggest that Zijuan tea could be a potential natural resource for the
      development of functional tea beverage. PRACTICAL APPLICATION: This study
      revealed that Zijuan tea extracts possessed anti-inflammatory, antiproliferative,
      and methylglyoxal trapping potentials in vitro. With high anthocyanins and
      polyphenols, Zijuan tea can be developed into a healthy tea beverage or used as a
      natural component to reduce the level of methylglyoxal in Maillard reaction.

PMID- 29337350
TI  - Alterations in mGlu5 receptor expression and function in the striatum in a rat
      depression model.
AB  - Major depressive disorder is a common form of mental illness. Many brain regions
      are implicated in the pathophysiology and symptomatology of depression. Among key
      brain areas is the striatum that controls reward and mood and is involved in the
      development of core depression-like behavior in animal models of depression.
      While molecular mechanisms in this region underlying depression-related behavior
      are poorly understood, the glutamatergic input to the striatum is believed to
      play a role. In this study, we investigated changes in metabotropic glutamate
      (mGlu) receptor expression and signaling in the striatum of adult rats in
      response to prolonged (10-12 weeks) social isolation, a pre-validated animal
      paradigm modeling depression in adulthood. We found that mGlu5 receptor protein
      levels in the striatum were increased in rats that showed typical depression- and
      anxiety-like behavior after chronic social isolation. This increase in mGlu5
      receptor expression was seen in both subdivisions of the striatum, the nucleus
      accumbens and caudate putamen. At subcellular and subsynaptic levels, mGlu5
      receptor expression was elevated in surface membranes at synaptic sites. In
      striatal neurons, the mGlu5-associated phosphoinositide signaling pathway was
      augmented in its efficacy after prolonged social isolation. These data indicate
      that the mGlu5 receptor is a sensitive substrate of depression. Adulthood social
      isolation leads to the up-regulation of mGlu5 receptor expression and function in
      striatal neurons.

PMID- 29337351
TI  - Selection of Yeast Strains for Tequila Fermentation Based on Growth Dynamics in
      Combined Fructose and Ethanol Media.
AB  - : The high concentration of fructose in agave juice has been associated with
      reduced ethanol tolerance of commercial yeasts used for tequila production and
      low fermentation yields. The selection of autochthonous strains, which are better
      adapted to agave juice, could improve the process. In this study, a 2-step
      selection process of yeasts isolated from spontaneous fermentations for tequila
      production was carried out based on analysis of the growth dynamics in combined
      conditions of high fructose and ethanol. First, yeast isolates (605) were
      screened to identify strains tolerant to high fructose (20%) and to ethanol
      (10%), yielding 89 isolates able to grow in both conditions. From the 89
      isolates, the growth curves under 8 treatments of combined fructose (from 20% to
      5%) and ethanol (from 0% to 10%) were obtained, and the kinetic parameters were
      analyzed with principal component analysis and k-means clustering. The resulting
      yeast strain groups corresponded to the fast, medium and slow growers. A second
      clustering of only the fast growers led to the selection of 3 Saccharomyces
      strains (199, 230, 231) that were able to grow rapidly in 4 out of the 8
      conditions evaluated. This methodology differentiated strains phenotypically and
      could be further used for strain selection in other processes. PRACTICAL
      APPLICATION: A method to select yeast strains for fermentation taking into
      account the natural differences of yeast isolates. This methodology is based on
      the cell exposition to combinations of sugar and ethanol, which are the most
      important stress factors in fermentation. This strategy will help to identify the
      most tolerant strain that could improve ethanol yield and reduce fermentation
      time.

PMID- 29337352
TI  - Genetic removal of eIF2alpha kinase PERK in mice enables hippocampal L-LTP
      independent of mTORC1 activity.
AB  - Characterization of the molecular signaling pathways underlying protein synthesis
      dependent forms of synaptic plasticity, such as late long-term potentiation (L
      LTP), can provide insights not only into memory expression/maintenance under
      physiological conditions but also potential mechanisms associated with the
      pathogenesis of memory disorders. Here, we report in mice that L-LTP failure
      induced by the mammalian (mechanistic) target of rapamycin complex 1 (mTORC1)
      inhibitor rapamycin is reversed by brain-specific genetic deletion of PKR-like ER
      kinase, PERK (PERK KO), a kinase for eukaryotic initiation factor 2alpha
      (eIF2alpha). In contrast, genetic removal of general control non-derepressible-2,
      GCN2 (GCN2 KO), another eIF2alpha kinase, or treatment of hippocampal slices with
      the PERK inhibitor GSK2606414, does not rescue rapamycin-induced L-LTP failure,
      suggesting mechanisms independent of eIF2alpha phosphorylation. Moreover, we
      demonstrate that phosphorylation of eukaryotic elongation factor 2 (eEF2) is
      significantly decreased in PERK KO mice but unaltered in GCN2 KO mice or slices
      treated with the PERK inhibitor. Reduction in eEF2 phosphorylation results in
      increased general protein synthesis, and thus could contribute to the mTORC1
      independent L-LTP in PERK KO mice. We further performed experiments on mutant
      mice with genetic removal of eEF2K (eEF2K KO), the only known kinase for eEF2,
      and found that L-LTP in eEF2K KO mice is insensitive to rapamycin. These data,
      for the first time, connect reduction in PERK activity with the regulation of
      translation elongation in enabling L-LTP independent of mTORC1. Thus, our
      findings indicate previously unrecognized levels of complexity in the regulation
      of protein synthesis-dependent synaptic plasticity. Read the Editorial Highlight
      for this article on page 119. Cover Image for this issue: doi: 10.1111/jnc.14185.

PMID- 29337353
TI  - Consumer Acceptance Comparison Between Seasoned and Unseasoned Vegetables.
AB  - : Recent findings show that approximately 87% of the U.S. population fail to meet
      the vegetable intake recommendations, with unpleasant taste of vegetables being
      listed as the primary reason for this shortfall. In this study, spice and herb
      seasoning was used to enhance palatability of vegetables, in order to increase
      consumer acceptance. In total, 749 panelists were screened and recruited as
      specific vegetable likers of the vegetable being tested or general vegetable
      likers. Four sessions were designed to evaluate the effect of seasoning within
      each type of vegetable, including broccoli, cauliflower, carrot, and green bean.
      Each panelist was only allowed to participate in one test session to evaluate
      only one vegetable type, so as to mitigate potential learning effect. Overall,
      the results showed that seasoned vegetables were significantly preferred over
      unseasoned vegetables (P < 0.001), indicating the sensory properties were
      significantly improved with seasoning. When general vegetable likers and specific
      vegetable likers were compared in terms of their preference between seasoned and
      unseasoned vegetables, the pattern varied across different vegetables; however,
      general trend of seasoned vegetable being preferred remained. The findings from
      this study demonstrate the effect of seasoning in enhancing consumer liking of
      vegetables, which may lead to increased consumption to be assessed in future
      studies. PRACTICAL APPLICATION: To improve the sensory properties of vegetables,
      masking the bitter taste of vegetables using spice and herb seasoning are gaining
      increasing attention. Our findings suggest that the overall liking of vegetables
      could be improved by incorporating spice and herb seasonings that are
      specifically formulated for each vegetable. Ultimately, developing and
      commercializing spice and herb seasonings may aid to increase vegetable
      consumption, as well as expanding the vegetable seasoning market.

PMID- 29337354
TI  - Current spring warming as a driver of selection on reproductive timing in a wild
      passerine.
AB  - Evolutionary adaptation as a response to climate change is expected for fitness
      related traits affected by climate and exhibiting genetic variance. Although the
      relationship between warmer spring temperature and earlier timing of reproduction
      is well documented, quantifications and predictions of the impact of global
      warming on natural selection acting on phenology in wild populations remain rare.
      If global warming affects fitness in a similar way across individuals within a
      population, or if fitness consequences are independent of phenotypic variation in
      key-adaptive traits, then no evolutionary response is expected for these traits.
      Here, we quantified the selection pressures acting on laying date during a 24
      year monitoring of blue tits in southern Mediterranean France, a hot spot of
      climate warming. We explored the temporal fluctuation in annual selection
      gradients and we determined its temperature-related drivers. We first
      investigated the month-specific warming since 1970 in our study site and tested
      its influence on selection pressures, using a model averaging approach. Then, we
      quantified the selection strength associated with temperature anomalies
      experienced by the blue tit population. We found that natural selection acting on
      laying date significantly fluctuated both in magnitude and in sign across years.
      After identifying a significant warming in spring and summer, we showed that
      warmer daily maximum temperatures in April were significantly associated with
      stronger selection pressures for reproductive timing. Our results indicated an
      increase in the strength of selection by 46% for every +1 degrees C anomaly. Our
      results confirm the general assumption that recent climate change translates into
      strong selection favouring earlier breeders in passerine birds. Our findings also
      suggest that differences in fitness among individuals varying in their breeding
      phenology increase with climate warming. Such climate-driven influence on the
      strength of directional selection acting on laying date could favour an adaptive
      response in this trait, since it is heritable.

PMID- 29337355
TI  - Moisture Adsorption Isotherm and Storability of Hazelnut Inshells and Kernels
      Produced in Oregon, USA.
AB  - : Moisture adsorption isotherms and storability of dried hazelnut inshells and
      kernels produced in Oregon were evaluated and compared among cultivars, including
      Barcelona, Yamhill, and Jefferson. Experimental moisture adsorption data fitted
      to Guggenheim-Anderson-de Boer (GAB) model, showing less hygroscopic properties
      in Yamhill than other cultivars of inshells and kernels due to lower content of
      carbohydrate and protein, but higher content of fat. The safe levels of moisture
      content (MC, dry basis) of dried inshells and kernels for reaching kernel water
      activity (aw ) <=0.65 were estimated using the GAB model as 11.3% and 5.0% for
      Barcelona, 9.4% and 4.2% for Yamhill, and 10.7% and 4.9% for Jefferson,
      respectively. Storage conditions (2  degrees C at 85% to 95% relative humidity
      [RH], 10  degrees C at 65% to 75% RH, and 27  degrees C at 35% to 45% RH), times
      (0, 4, 8, or 12 mo), and packaging methods (atmosphere vs. vacuum) affected MC,
      aw , bioactive compounds, lipid oxidation, and enzyme activity of dried hazelnut
      inshells or kernels. For inshells packaged at woven polypropylene bag, MC and aw
      of inshells and kernels (inside shells) increased at 2 and 10  degrees C, but
      decreased at 27  degrees C during storage. For kernels, lipid oxidation and
      polyphenol oxidase activity also increased with extended storage time (P < 0.05),
      and MC and aw of vacuum packaged samples were more stable during storage than
      those atmospherically packaged ones. Principal component analysis showed
      correlation of kernel qualities with storage condition, time, and packaging
      method. This study demonstrated that the ideal storage condition or packaging
      method varied among cultivars due to their different moisture adsorption and
      physicochemical and enzymatic stability during storage. PRACTICAL APPLICATION:
      Moisture adsorption isotherm of hazelnut inshells and kernels is useful for
      predicting the storability of nuts. This study found that water adsorption and
      storability varied among the different cultivars of nuts, in which Yamhill was
      less hygroscopic than Barcelona and Jefferson, thus more stable during storage.
      For ensuring food safety and quality of nuts during storage, each cultivar of
      kernels should be dried to a certain level of MC. Lipid oxidation and enzyme
      activity of kernel could be increased with extended storage time. Vacuum
      packaging was recommended to kernels for reducing moisture adsorption during
      storage.

PMID- 29337356
TI  - Stabilizing selection on sperm number revealed by artificial selection and
      experimental evolution.
AB  - Sperm competition is taxonomically widespread in animals and is usually
      associated with large sperm production, being the number of sperm in the
      competing pool the prime predictor of fertilization success. Despite the strong
      postcopulatory selection acting directionally on sperm production, its genetic
      variance is often very high. This can be explained by trade-offs between sperm
      production and traits associated with mate acquisition or survival, that may
      contribute to generate an overall stabilizing selection. To investigate this
      hypothesis, we first artificially selected male guppies (Poecilia reticulata) for
      high and low sperm production for three generations, while simultaneously
      removing sexual selection. Then, we interrupted artificial selection and restored
      sexual selection. Sperm production responded to divergent selection in one
      generation, and when we restored sexual selection, both high and low lines
      converged back to the mean sperm production of the original population within two
      generations, indicating that sperm number is subject to strong stabilizing total
      sexual selection (i.e., selection acting simultaneously on all traits associated
      with reproductive success). We discuss the possible mechanisms responsible for
      the maintenance of high genetic variability in sperm production despite strong
      selection acting on it.

PMID- 29337363
TI  - Inhibition of apoptosis using exosomes in Chinese hamster ovary cell culture.
AB  - Animal cell culture technology for therapeutic protein production has shown
      significant improvement over the last few decades. Chinese hamster ovary (CHO)
      cells have been widely adapted for the production of biopharmaceutical drugs. In
      the biopharmaceutical industry, it is crucial to develop cell culture media and
      culturing conditions to achieve the highest productivity and quality. However,
      CHO cells are significantly affected by apoptosis in the bioreactors, resulting
      in a substantial decrease in product quantity and quality. Thus, to overcome the
      obstacle of apoptosis in CHO cell culture, it is critical to develop a novel
      method that does not have minimal concern of safety or cost. Herein, we showed
      for the first time that exosomes, which are nano-sized extracellular vesicles,
      derived from CHO cells inhibited apoptosis in CHO cell culture when supplemented
      to the culture medium. Flow cytometric and microscopic analyses revealed that
      substantial amounts of exosomes were delivered to CHO cells. Higher cell
      viability after staurosporine treatment was observed by exosome supplementation
      (67.3%) as compared to control (41.1%). Furthermore, exosomes prevented the
      mitochondrial membrane potential loss and caspase-3 activation, meaning that the
      exosomes enhanced cellular activities under pro-apoptotic condition. As the
      exosomes supplements are derived from CHO cells themselves, it is not only
      beneficial for the biopharmaceutical productivity of CHO cell culture to inhibit
      apoptosis, but also from a regulatory standpoint to diminish any safety concerns.
      Thus, we conclude that the method developed in this research may contribute to
      the biopharmaceutical industry where minimizing apoptosis in CHO cell culture is
      beneficial.

PMID- 29337364
TI  - The Function of Emulsions on the Biogenic Amine Formation and their Indices of
      Sea Bass Fillets (Dicentrarchus Labrax) Stored in Vacuum Packaging.
AB  - : The impacts of emulsions based on commercial oils on the biogenic amine
      formation and their indices of vacuumed packed sea bass fillets were
      investigated. The results showed that among biogenic amines, cadaverine,
      putrescine, spermidine, spermine, serotonin, dopamine, and agmatine were
      predominant amines in sea bass fillets stored under vacuum packaging. Significant
      differences (P < 0.05) in biogenic amines concentrations of vacuumed packed sea
      bass treated with emulsions were observed. All groups contained histamine lower
      than 5.0 mg/100 g, regarded as the allowable limit by the U.S. Food and Drug
      Administration. Polyamine levels were not affected by application of emulsion.
      Quality index (QI) showed an increase and after 14 d of storage it decreased in
      all groups. The control generally seemed to higher QI value than those of
      treatment groups except at 14 and 18 days while soybean and corn gave lower QI
      among treatment groups. Only biogenic amine index correlated with sensory
      acceptability of vacuumed packed sea bass, indicating that this index can be used
      for determination of the degree of spoilage of vacuumed packed sea bass.
      Emulsions extended the shelf-life (approximately 2 to 4 d) of vacuumed packed sea
      bass fillets by inhibiting microbial growth compared to the control. PRACTICAL
      APPLICATION: Emulsions have become popular since they are regarded as ideal
      carrier for the delivery of lipophilic substances due to the ease of preparation,
      small particle size, their enhanced bioavailability, and long term kinetic
      stability. They have been proven to be self-preserving antimicrobials due to
      bound water in their structure and thus no available water to microorganisms.
      Antimicrobial emulsions have potential applications in many fields because they
      are inexpensive, stable, and nontoxic agents.

PMID- 29337365
TI  - Loss of STI1-mediated neuronal survival and differentiation in disease-associated
      mutations of prion protein.
AB  - Cellular prion protein (PrPC ) is widely expressed and displays a variety of well
      described functions in the central nervous system (CNS). Mutations of the PRNP
      gene are known to promote genetic human spongiform encephalopathies, but the
      components of gain- or loss-of-function mutations to PrPC remain a matter for
      debate. Among the proteins described to interact with PrPC is Stress-inducible
      protein 1 (STI1), a co-chaperonin that is secreted from astrocytes and triggers
      neuroprotection and neuritogenesis through its interaction with PrPC . In this
      work, we evaluated the impact of different PrPC pathogenic point mutations on
      signaling pathways induced by the STI1-PrPC interaction. We found that some of
      the pathogenic mutations evaluated herein induce partial or total disruption of
      neuritogenesis and neuroprotection mediated by mitogen-activated protein kinase
      (MAPK)/extracellular signal-regulated kinases 1 and 2 (ERK1/2) and protein kinase
      A (PKA) signaling triggered by STI1-PrPC engagement. A pathogenic mutant PrPC
      that lacked both neuroprotection and neuritogenesis activities fail to promote
      negative dominance upon wild-type PrPC . Also, a STI1-alpha7-nicotinic
      acetylcholine receptor-dependent cellular signaling was present in a PrPC mutant
      that maintained both neuroprotection and neuritogenesis activities similar to
      what has been previously observed by wild-type PrPC . These results point to a
      loss-of-function mechanism underlying the pathogenicity of PrPC mutations.

PMID- 29337366
TI  - Replenishment of Docosahexaenoic Acid (DHA) in Dietary n-3-Deficient Mice Fed DHA
      in Triglycerides or Phosphatidylcholines After Weaning.
AB  - : Previous studies have shown that DHA in triglyceride (TG) and
      phosphatidylcholine (PC) forms are different in their bioavailability. The aim of
      this study was to investigate the comparative effects of DHA-TG and DHA-PC on
      tissue DHA accretion in dietary n-3 polyunsaturated fatty acid deficient (n-3
      Def) mice. The mice were fed with n-3 Def diet containing DHA-TG or DHA-PC (5
      g/kg diet) for 2, 4, 7, or 14 d after weaning, respectively. The DHA levels in
      the cortex, liver, testis, and erythrocytes were analyzed by gas chromatography.
      For liver, DHA mainly existed in hepatic phospholipids relative to triglycerides.
      Both DHA-TG and DHA-PC could recover the hepatic DHA to a normal level.
      Interestingly, DHA-TG was more effective in increasing the DHA level in hepatic
      triglycerides, and DHA-PC was more effective in increasing the DHA level in
      hepatic phospholipids. For erythrocytes, during the first 7 d, no difference was
      observed after dietary DHA-TG and DHA-PC but a significantly higher DHA
      percentage was detected in the DHA-PC group after 14 d. For cortex, the DHA-TG
      group showed a higher cortical DHA level at the 4th day, but the DHA-PC group
      showed a higher cortical DHA level with a greater slope from Day 7 to Day 14, and
      the same trend was observed in testis. But unexpectedly, the DHA level in testis
      showed a downtrend from Day 7 to Day 14. This study suggests that, under dietary
      n-3-deficient condition, both DHA-TG and DHA-PC could recover the DHA level in
      tissues after weaning, and DHA-PC showed a better supplemental effect. PRACTICAL
      APPLICATION: Dietary DHA is essential for neurodevelopment which is usually
      accompanied by large amounts of DHA accretion in the brain. Our present study
      showed that DHA-PC had a better efficiency for DHA accretion in the brain and
      other tissues compared with DHA-TG. The findings are supposed to pave the way for
      the DHA in phospholipids as a novel nutrient added into the infant formula and
      assisted food for neurodevelopment.

PMID- 29337367
TI  - Correlation of simulation/finite element analysis to the separation of
      intrinsically magnetic spores and red blood cells using a microfluidic magnetic
      deposition system.
AB  - Magnetic separation of cells has been, and continues to be, widely used in a
      variety of applications, ranging from healthcare diagnostics to detection of food
      contamination. Typically, these technologies require cells labeled with antibody
      magnetic particle conjugate and a high magnetic energy gradient created in the
      flow containing the labeled cells (i.e., a column packed with magnetically
      inducible material), or dense packing of magnetic particles next to the flow
      cell. Such designs, while creating high magnetic energy gradients, are not
      amenable to easy, highly detailed, mathematic characterization. Our laboratories
      have been characterizing and developing analysis and separation technology that
      can be used on intrinsically magnetic cells or spores which are typically orders
      of magnitude weaker than typically immunomagnetically labeled cells. One such
      separation system is magnetic deposition microscopy (MDM) which not only
      separates cells, but deposits them in specific locations on slides for further
      microscopic analysis. In this study, the MDM system has been further
      characterized, using finite element and computational fluid mechanics software,
      and separation performance predicted, using a model which combines: 1) the
      distribution of the intrinsic magnetophoretic mobility of the cells (spores); 2)
      the fluid flow within the separation device; and 3) accurate maps of the values
      of the magnetic field (max 2.27 T), and magnetic energy gradient (max of 4.41 T2
      /mm) within the system. Guided by this model, experimental studies indicated that
      greater than 95% of the intrinsically magnetic Bacillus spores can be separated
      with the MDM system. Further, this model allows analysis of cell trajectories
      which can assist in the design of higher throughput systems.

PMID- 29337368
TI  - Stability and Antioxidant Activity of Annatto (Bixa orellana L.) Tocotrienols
      During Frying and in Fried Tortilla Chips.
AB  - : Annatto tocotrienols (AnT3), which contain approximately 90% delta-tocotrienol
      (delta-T3), were added to mid-oleic sunflower oil used for frying tortilla chips
      over 3 d. The objectives were to evaluate their stability during frying,
      absorption by the fried food, and activity as antioxidants in frying oil and in
      tortilla chips during storage. AnT3 did not significantly affect the stability of
      the oil during frying or the sensory profiles of freshly fried chips. The
      naturally present alpha-tocopherol (alpha-T) in the oil degraded at a lower rate
      in the presence of AnT3, resulting in significantly higher alpha-T by the end of
      the frying study. Levels of tocopherols and tocotrienols in the chips mirrored
      oil levels. AnT3 did not affect the sensory profile of the chips after 1 wk of
      storage at 50  degrees C, but after 3 wk of storage, the control chips had higher
      levels of painty and rancid flavors compared to chips with AnT3. Headspace
      hexanal was also significantly higher in the control chips compared to the chips
      with AnT3 after 3 wk of storage. PRACTICAL APPLICATION: Annatto tocotrienols,
      containing primarily delta- and gamma-tocotrienols, were added to mid-oleic
      sunflower oil used for frying tortilla chips. The tocotrienols were absorbed by
      the chips along with the oil. They slowed the degradation of alpha tocopherol
      during frying, and reduced levels of painty and rancid flavor scores as well as
      headspace hexanal in chips that were stored for 3 wk at elevated temperatures.
      The results indicated that fried snack foods such as tortilla chips may be a
      suitable and convenient vehicle for enriching tocotrienols in the diet, and that
      tocotrienols may also enhance the shelf-life of fried foods.

PMID- 29337369
TI  - Hepatoprotective Effects of the Honey of Apis cerana Fabricius on Bromobenzene
      Induced Liver Damage in Mice.
AB  - Apis cerana honey (honey of Apis cerana Fabricius), widely distributed in the
      mountain areas of East Asia, has not been studied fully. The hepatoprotective
      activity of A. cerana honey was evaluated against bromobenzene-induced liver
      damage in mice. In high dose, A. cerana honey can significantly alleviate liver
      injury, as is indicated by the depressed levels of serum alanine aminotransferase
      (ALT) (59.13%) and aspartate aminotransferase (AST) (79.71%), the inhibited
      malondialdehyde (MDA) content (63.30%), the elevated activities of superoxide
      dismutase (SOD) (73.12%) and glutathione-Px (57.24%), and the decreased
      expression of Transforming growth factor beta1 (51.83%) induced by bromobenzene
      (P < 0.05). The quantitative analysis of twelve major constituents (1 to 12) of
      A. cerana honey was executed by high performance liquid chromatography-diode
      array detector. The results indicate that treatment with A. cerana honey can
      prevent bromobenzene-induced hepatic damage in mice. Polyphenols might be the
      bioactive substances attributed to its antioxidant properties and intervention of
      oxidative stress.

PMID- 29337371
TI  - Avian Retrovirus-Mediated Tumor-Specific Gene Knockout.
AB  - The RCAS (replication-competent avian sarcoma leukosis virus long-terminal repeat
      with splice acceptor)-TVA (tumor virus A) gene delivery system has been
      successfully used in modeling human cancers. Based on this, we have recently
      developed a novel RCI-Oncogene (RCAS-Cre-IRES-Oncogene) gene delivery system that
      can be used to efficiently manipulate gene expression in spontaneous tumors in
      vivo. We used this system for tumor gene knockout (TuKO) and demonstrated a
      crucial role of FGFR1 in driving mammary tumor metastasis. This versatile tumor
      gene modification system can also be adapted into different configurations to
      address different questions in appropriate mutant mouse hosts. Here we describe a
      protocol using the TuKO approach to knock out a gene of interest in tumors in
      appropriate hosts. (c) 2018 by John Wiley & Sons, Inc.

PMID- 29337370
TI  - Modulating Gene Expression in Epstein-Barr Virus (EBV)-Positive B Cell Lines with
      CRISPRa and CRISPRi.
AB  - Epstein-Barr virus (EBV) transforms small resting primary B cells into large
      lymphoblastoid cells which are able to grow and survive in vitro indefinitely.
      These cells represent a model for oncogenesis. In this unit, variants of
      conventional clustered regularly interspaced short palindromic repeats (CRISPR),
      namely the CRISPR activation (CRISPRa) and CRISPR interference (CRISPRi) methods,
      are discussed in the context of gene regulation at genomic DNA promoter and
      enhancer elements. Lymphoblastoid B cell lines (LCLs) stably expressing nuclease
      deficient Cas9 (dCas9)-VP64 (Cas9 associated with CRISPRa) or dCas9-KRAB (Cas9
      associated with CRISPRi) are transduced with lentivirus that encodes a single
      guide RNA (sgRNA) that targets a specific gene locus. The ribonucleoprotein
      complex formed by the dCas9 molecule and its cognate sgRNA enables sequence
      specific binding at a promoter or enhancer of interest to affect the expression
      of genes regulated by the targeted promoter or enhancer. (c) 2018 by John Wiley &
      Sons, Inc.

PMID- 29337372
TI  - CRISPR-Cas9-Edited Site Sequencing (CRES-Seq): An Efficient and High-Throughput
      Method for the Selection of CRISPR-Cas9-Edited Clones.
AB  - The emergence of clustered regularly interspaced short palindromic repeats-Cas9
      (CRISPR-Cas9) gene editing systems has enabled the creation of specific mutants
      at low cost, in a short time and with high efficiency, in eukaryotic cells. Since
      a CRISPR-Cas9 system typically creates an array of mutations in targeted sites, a
      successful gene editing project requires careful selection of edited clones. This
      process can be very challenging, especially when working with multiallelic genes
      and/or polyploid cells (such as cancer and plants cells). Here we described a
      next-generation sequencing method called CRISPR-Cas9 Edited Site Sequencing (CRES
      Seq) for the efficient and high-throughput screening of CRISPR-Cas9-edited
      clones. CRES-Seq facilitates the precise genotyping up to 96 CRISPR-Cas9-edited
      sites (CRES) in a single MiniSeq (Illumina) run with an approximate sequencing
      cost of $6/clone. CRES-Seq is particularly useful when multiple genes are
      simultaneously targeted by CRISPR-Cas9, and also for screening of clones
      generated from multiallelic genes/polyploid cells. (c) 2018 by John Wiley & Sons,
      Inc.

PMID- 29337373
TI  - Making Use of Cancer Genomic Databases.
AB  - The vast amounts of genomic data now deposited in public repositories represent
      rich resources for cancer researchers. Large-scale genomics initiatives such as
      The Cancer Genome Atlas have made available data from multiple molecular
      profiling platforms (e.g., somatic mutation, RNA and protein expression, and DNA
      methylation) for the same set of over 10,000 human tumors. There has been much
      collective effort toward providing user-friendly software tools for biologists
      lacking computational skills to ask questions of large-scale genomic datasets. At
      the same time, there remains a clear need for skilled bioinformatics analysts to
      answer the types of questions that cannot easily be addressed using the public
      user-friendly software tools. This overview introduces the reader to the many
      resources available for working with cancer genomic databases. (c) 2018 by John
      Wiley & Sons, Inc.

PMID- 29337374
TI  - Pooled Lentiviral-Delivery Genetic Screens.
AB  - Pooled cell-based screens of mammalian genetic perturbations enable systematic
      large-scale, even genome-scale, evaluation of gene function. Pooled screens
      introduce genetic perturbations into a cell population through viral transduction
      such that each cell integrates into its DNA a single or small number of library
      perturbations with barcodes identifying the perturbations. One then selects and
      physically isolates the subset of cells that exhibit the phenotype of interest.
      Sequencing the barcodes in the hit cells reveals which genes favored or inhibited
      the hit phenotype. Various genetic perturbations are possible, including CRISPR
      gene knockout, ectopic gene expression, and RNA interference. Regardless of the
      type of library being screened or the type of cell model being tested, such
      screens involve many common steps and procedures. This unit describes detailed
      experimental protocols for the key steps, and also highlights some of the key
      factors to achieving a well-powered, reproducible screen result. (c) 2018 by John
      Wiley & Sons, Inc.

PMID- 29337375
TI  - Transfection by Electroporation.
AB  - Electroporation-the use of high-voltage electric shocks to introduce DNA into
      cells-can be used with most cell types, yields a high frequency of both stable
      transformation and transient gene expression, and, because it requires fewer
      steps, can be easier than alternate techniques. This unit describes
      electroporation of mammalian cells, including ES cells for the preparation of
      knock-out, knock-in, and transgenic mice. Protocols are described for the use of
      electroporation in vivo to perform gene therapy for cancer therapy and DNA
      vaccination. Also described are modifications for preparation and transfection of
      plant protoplasts. (c) 2018 by John Wiley & Sons, Inc.

PMID- 29337376
TI  - CRISPR/Cas9-Mediated Genome Editing in Epstein-Barr Virus-Transformed
      Lymphoblastoid B-Cell Lines.
AB  - Epstein-Barr virus (EBV) efficiently transforms primary human B cells into
      immortalized lymphoblastoid cell lines (LCLs), which are extensively used in
      human genetic, immunological and virological studies. LCLs provide unlimited
      sources of DNA for genetic investigation, but can be difficult to manipulate, for
      instance because low retroviral or lentiviral transduction frequencies hinder
      experiments that require co-expression of multiple components. This unit details
      Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9
      engineering for robust LCL genome editing. We describe the generation and
      delivery of single-guide RNAs (sgRNAs), or dual-targeting sgRNAs, via lentiviral
      transduction of LCLs that stably express Cas9 protein. CRISPR/Cas9 editing allows
      LCL loss-of-function studies, including knock-out of protein-coding genes or
      deletion of DNA regulatory elements, and can be adapted for large-scale screening
      approaches. Low transfection efficiencies are a second barrier to performing
      CRISPR editing in LCLs, which are not typically lipid-transfectable. To
      circumvent this barrier, we provide an optimized protocol for LCL nucleofection
      of Cas9/sgRNA ribonucleoprotein complexes (RNPs) as an alternative route to
      achieve genome editing in LCLs. These editing approaches can also be employed in
      other B-cell lines, including Burkitt lymphoma and diffuse large B-cell lymphoma
      cells, and are highly reproducible. (c) 2018 by John Wiley & Sons, Inc.

PMID- 29337377
TI  - Ultrafast Laser-Shock-Induced Confined Metaphase Transformation for Direct
      Writing of Black Phosphorus Thin Films.
AB  - Few-layer black phosphorus (BP) has emerged as one of the most promising
      candidates for post-silicon electronic materials due to its outstanding
      electrical and optical properties. However, lack of large-scale BP thin films is
      still a major roadblock to further applications. The most widely used methods for
      obtaining BP thin films are mechanical exfoliation and liquid exfoliation.
      Herein, a method of directly synthesizing continuous BP thin films with the
      capability of patterning arbitrary shapes by employing ultrafast laser writing
      with confinement is reported. The physical mechanism of confined laser metaphase
      transformation is understood by molecular dynamics simulation. Ultrafast laser
      ablation of BP layer under confinement can induce transient nonequilibrium high
      temperature and high-pressure conditions for a few picoseconds. Under optimized
      laser intensity, this process induces a metaphase transformation to form a
      crystalline BP thin film on the substrate. Raman spectroscopy, atomic force
      microscopy, and transmission electron microscopy techniques are utilized to
      characterize the morphology of the resulting BP thin films. Field-effect
      transistors are fabricated on the BP films to study their electrical properties.
      This unique approach offers a general methodology to mass produce large-scale
      patterned BP films with a one-step manufacturing process that has the potential
      to be applied to other 2D materials.

PMID- 29337378
TI  - Resemblance of a model species and its mimic: Response to Bury and Cichon.

PMID- 29337379
TI  - Interleukin-17A and vascular remodelling in severe asthma; lack of evidence for a
      direct role.
AB  - BACKGROUND: Bronchial vascular remodelling may contribute to the severity of
      airway narrowing through mucosal congestion. Interleukin (IL)-17A is associated
      with the most severe asthmatic phenotype but whether it might contribute to
      vascular remodelling is uncertain. OBJECTIVE: To assess vascular remodelling in
      severe asthma and whether IL-17A directly or indirectly may cause endothelial
      cell activation and angiogenesis. METHODS: Bronchial vascularization was
      quantified in asthmatic subjects, COPD and healthy subjects together with the
      number of IL-17A+ cells as well as the concentration of angiogenic factors in the
      sputum. The effect of IL-17A on in vitro angiogenesis, cell migration and
      endothelial permeability was assessed directly on primary human lung
      microvascular endothelial cells (HMVEC-L) or indirectly with conditioned medium
      derived from normal bronchial epithelial cells (NHBEC), fibroblasts (NHBF) and
      airway smooth muscle cells (ASMC) after IL-17A stimulation. RESULTS: Severe
      asthmatics have increased vascularity compared to the other groups, which
      correlates positively with the concentrations of angiogenic factors in sputum.
      Interestingly, we demonstrated that increased bronchial vascularity correlates
      positively with the number of subepithelial IL-17A+ cells. However IL-17A had no
      direct effect on HMVEC-L function but it enhanced endothelial tube formation and
      cell migration through the production of angiogenic factors by NHBE and ASMC.
      CONCLUSIONS & CLINICAL RELEVANCE: Our results shed light on the role of IL-17A in
      vascular remodelling, most likely through stimulating the synthesis of other
      angiogenic factors. Knowledge of these pathways may aid in the identification of
      new therapeutic targets.

PMID- 29337380
TI  - Recent Advances in Micro-/Nanostructured Metal-Organic Frameworks towards
      Photonic and Electronic Applications.
AB  - Micro- and nanometer-sized metal-organic frameworks (MOFs) materials have
      attracted great attention due to their unique properties and various potential
      applications in photonics, electronics, high-density storage, chemo-, and
      biosensors. The study of these materials supplies insight into how the crystal
      structure, molecular components, and micro-/nanoscale effects can influence the
      performance of inorganic-organic hybrid materials. In this Minireview article, we
      introduce recent breakthroughs in the controlled synthesis of MOF micro
      /nanomaterials with specific structures and compositions, the tunable photonic
      and electronic properties of which would provide a novel platform for
      multifunctional applications. Firstly, the design strategies for MOFs based on
      self-assembly and crystal engineering principles are introduced. Attention is
      then focused on the methods of fabrication of low-dimensional MOF micro
      /nanostructures. Their new applications including two-photon excited
      fluorescence, multi-photon pumped lasing, optical waveguides, nonlinear optical
      (NLO), and field-effect transistors are also outlined. Finally, we briefly
      discuss perspectives on the further development of these hybrid crystalline micro
      /nanomaterials.

PMID- 29337381
TI  - A Combined Photochemical and Multicomponent Reaction Approach to Precision
      Oligomers.
AB  - We introduce the convergent synthesis of linear monodisperse sequence-defined
      oligomers through a unique approach, combining the Passerini three-component
      reaction (P-3CR) and a Diels-Alder (DA) reaction based on photocaged dienes. A
      set of oligomers is prepared resting on a Passerini linker unit carrying an
      isocyano group for chain extension by P-3CR and a maleimide moiety for photoenol
      conjugation enabling a modular approach for chain growth. Monodisperse oligomers
      are accessible in a stepwise fashion by switching between both reaction types.
      Employing sebacic acid as a core unit allows the synthesis of a library of
      symmetric sequence-defined oligomers. The oligomers consist of alternating P-3CR
      and photoblocks with molecular weights up to 3532.16 g mol-1 , demonstrating the
      successful switching from P-3CR to photoenol conjugation. In-depth
      characterization was carried out including size-exclusion chromatography (SEC),
      high-resolution electrospray ionization mass spectrometry (ESI-MS) and NMR
      spectroscopy, evidencing the monodisperse nature of the precision oligomers.

PMID- 29337382
TI  - Frailty in patients with acute myeloid leukaemia, conceptual misapprehension of
      chronological age.
AB  - In haematology practice, patients with acute myeloid leukaemia (AML) are
      generally assessed for frailty only if they are older and not able to tolerate
      intensive and remission targeted treatments. We aimed to focus on frailty in
      patients with AML, in all ages and aimed to evaluate its role and practicality in
      daily routine. Data of patients diagnosed and treated for AML between 2006 and
      2016 are recorded and assessed for their survival predictivity. One hundred and
      ninety-seven patients were <65 years of age and 175 were >=65. Majority of the
      younger patients showed ECOG 2 performance (119, 60.4%). Combined with ECOG
      scale, G8 scale showed survival predictivity in younger patients as well as older
      patients. Nutritional status showed a strong predictivity in younger patients
      while remained insignificant in older patients. VES13 scale showed similar
      predictivity strength for survival in both age groups (p = .001). Young AML
      patients should be thoroughly evaluated as older patients. ECOG performance
      evaluation should be supported with further scales. Young patients with lower
      ECOG scores may be regarded as vulnerable with scales embracing dimensions such
      as nutrition, perception of disease, depression and cognition. Nutrition should
      be within the main goals of intensive treatment and is related with survival.

PMID- 29337383
TI  - Pregnancy in Diabetes: challenges and opportunities for improving pregnancy
      outcomes.
AB  - Our aim was to review the data from the National Pregnancy in Diabetes (NPID)
      audit, and to identify the challenges and opportunities for improving pregnancy
      outcomes in women with diabetes. We reviewed three years of NPID data and
      relevant diabetes and obstetric literature, and found that there has been little
      change in pregnancy preparation or outcomes over the past 3 years, with
      substantial clinic-to clinic variations in care. Women with Type 2 diabetes
      remain less likely to take 5 mg preconception folic acid (22.8% vs. 41.8%; P <
      0.05), and more likely to take potentially harmful medications (statin and/or ACE
      inhibitor 13.0% vs. 1.8%; P < 0.05) than women with Type 1 diabetes. However,
      women with Type 1 diabetes are less likely to achieve the recommended glucose
      control target of HbA1c < 48 mmol/mol (6.5%) (14.9% vs. 38.1%; P < 0.05). The
      following opportunities for improvement were identified. First, the need to
      integrate reproductive health into the diabetes care plans of all women with
      diabetes aged 15-50 years. Second, to develop more innovative approaches to
      improve uptake of pre-pregnancy care in women with Type 2 diabetes in primary
      care settings. Third, to integrate insulin pump, continuous glucose monitoring
      and automated insulin delivery technologies into the pre-pregnancy and antenatal
      care of women with Type 1 diabetes. Fourth, to improve postnatal care with
      personalized approaches targeting women with previous pregnancy loss, congenital
      anomaly and perinatal mortality. A nationwide commitment to delivering integrated
      reproductive and diabetes healthcare interventions is needed to improve the
      health outcomes of women with diabetes.

PMID- 29337384
TI  - Dual-hormone artificial pancreas: benefits and limitations compared with single
      hormone systems.
AB  - Technological advances have made the artificial pancreas a reality. This has the
      potential to improve the lives of individuals with Type 1 diabetes by reducing
      the risk of hypoglycaemia, achieving better overall glucose control, and
      enhancing quality of life. Both single-hormone (insulin-only) and dual-hormone
      (insulin and glucagon) systems have been developed; however, a focused review of
      the relative benefits of each artificial pancreas system is needed. We reviewed
      studies that directly compared single- and dual-hormone systems to evaluate the
      efficacy of each system for preventing hypoglycaemia and maintaining glycaemic
      control, as well as their utility in specific situations including during
      exercise, overnight and during the prandial period. We observed additional
      benefits with the dual-hormone artificial pancreas for reducing the risk of
      hypoglycaemic events overall and during exercise over the study duration. The
      single-hormone artificial pancreas was sufficient for maintenance of euglycaemia
      in the overnight period and for preventing late-onset post-exercise
      hypoglycaemia. Future comparative studies of longer duration are required to
      determine whether one system is superior for improving mean glucose control,
      eliminating severe hypoglycaemia, or improving quality of life.

PMID- 29337385
TI  - Orientation-Dependent Strain Relaxation and Chemical Functionalization of
      Graphene on a Cu(111) Foil.
AB  - Epitaxial graphene grown on single crystal Cu(111) foils by chemical vapor
      deposition is found to be free of wrinkles and under biaxial compressive strain.
      The compressive strain in the epitaxial regions (0.25-0.40%) is higher than
      regions where the graphene is not epitaxial with the underlying surface (0.20
      0.25%). This orientation-dependent strain relaxation is through the loss of local
      adhesion and the generation of graphene wrinkles. Density functional theory
      calculations suggest a large frictional force between the epitaxial graphene and
      the Cu(111) substrate, and this is therefore an energy barrier to the formation
      of wrinkles in the graphene. Enhanced chemical reactivity is found in epitaxial
      graphene on Cu(111) foils as compared to graphene on polycrystalline Cu foils for
      certain chemical reactions. A higher compressive strain possibly favors lowering
      the formation energy and/or the energy gap between the initial and transition
      states, either of which can lead to an increase in chemical reactivity.

PMID- 29337386
TI  - Synthesis and X-Ray Crystallographic Characterisation of Frustum-Shaped Ligated
      [Cu18 H16 (DPPE)6 ]2+ and [Cu16 H14 (DPPA)6 ]2+ Nanoclusters and Studies on Their
      H2 Evolution Reactions.
AB  - We report new structural motifs for Cu nanoclusters that conceptually represent
      seed crystals for large face-centred cubic (FCC) crystal growth. Kinetically
      controlled syntheses, high resolution mass spectrometry experiments for
      determination of the dication formulae and crystallographic characterisation were
      carried out for [Cu18 H16 (DPPE)6 ][BF4 ][Cl] (DPPE=bis(diphenylphosphino)ethane)
      and [Cu16 H14 (DPPA)6 ][(BF4 )2 ] (DPPA=bis(diphenylphosphino)amine) polyhydrido
      nanoclusters, which feature the unprecedented bifrustum and frustum metal-core
      architecture in metal nanoclusters. The Cu18 nanocluster contains two Cu9 frustum
      cupolae and the Cu16 nanocluster has one Cu9 frustum cupola and a Cu7 distorted
      hexagonal-shape base. Gas-phase experiments revealed that both Cu18 H16 and Cu16
      H14 cores can spontaneously release H2 upon removal of one bisphosphine capping
      ligand.

PMID- 29337388
TI  - Reactions of an Aluminium/Phosphorus Frustrated Lewis Pair (FLP) with alpha,beta
      Unsaturated Carbonyl Compounds: FLPs as Efficient Two-Electron Reductants with
      the Formation of Enolates, a cis-Enediolate, and an Allene.
AB  - The Al/P-based frustrated Lewis pair (FLP) Mes2 P-C(AltBu)2 =C(H)Ph (1;
      Mes=mesityl) reacted as an efficient two-electron reductant with benzil to afford
      a cis-enediolate that was coordinated to the FLP through P-O and Al-O bonds and
      the formation of a seven-membered heterocycle (2). The phosphorus atom is
      oxidised from +III to +V. Similar heterocycles (3 a to 3 f) were formed if 1 was
      treated with various enones (acrolein, acrylate, acrylamide). The resulting
      enolates are bound to the FLP through P-C and Al-O bonds. Cyclopropenone gave an
      adduct (4) with the C=O bond coordinated by P and Al. Ynones gave a fascinating
      variety of different structures. 1,3-Diphenylprop-2-yn-1-one afforded a
      remarkable allene-type moiety with two cumulated C=C bonds (5); 3-hexyn-2-one
      yielded a ligand with two conjugated C=C bonds by C-H bond activation at the
      carbonyl methyl group (7); and 4-(trimethylsilyl)-3-butyn-2-one reacted by C-H
      bond cleavage, formation of an enolate group with a terminal C=C bond, and shift
      of the proton to the P atom (8). The C=C bond was not affected. Allene compound 5
      rearranged at elevated temperature and in daylight through the formation of a
      tricyclic compound by C-H bond activation and C-C bond formation. DFT
      calculations on this unusual rearrangement suggest insertion of the central
      allene C atom into the C-H bond of a methyl group and the intermediate formation
      of a C3 ring.

PMID- 29337387
TI  - Systematic review of predictive risk models for adverse drug events in
      hospitalized patients.
AB  - AIM: An emerging approach to reducing hospital adverse drug events is the use of
      predictive risk scores. The aim of this systematic review was to critically
      appraise models developed for predicting adverse drug event risk in inpatients.
      METHODS: Embase, PubMed, CINAHL and Scopus databases were used to identify
      studies of predictive risk models for hospitalized adult inpatients. Studies had
      to have used multivariable logistic regression for model development, resulting
      in a score or rule with two or more variables, to predict the likelihood of
      inpatient adverse drug events. The Checklist for the critical Appraisal and data
      extraction for systematic Reviews of prediction Modelling Studies (CHARMS) was
      used to critically appraise eligible studies. RESULTS: Eleven studies met the
      inclusion criteria and were included in the review. Ten described the development
      of a new model, whilst one study revalidated and updated an existing score.
      Studies used different definitions for outcome but were synonymous with or
      closely related to adverse drug events. Four studies undertook external
      validation, five internally validated and two studies did not validate their
      model. No studies evaluated impact of risk scores on patient outcomes.
      CONCLUSION: Adverse drug event risk prediction is a complex endeavour but could
      help to improve patient safety and hospital resource management. Studies in this
      review had some limitations in their methods for model development, reporting and
      validation. Two studies, the BADRI and Trivalle's risk scores, used better model
      development and validation methods and reported reasonable performance, and so
      could be considered for further research.

PMID- 29337389
TI  - Thiazole Imide-Based All-Acceptor Homopolymer: Achieving High-Performance
      Unipolar Electron Transport in Organic Thin-Film Transistors.
AB  - High-performance unipolar n-type polymer semiconductors are critical for
      advancing the field of organic electronics, which relies on the design and
      synthesis of new electron-deficient building blocks with good solubilizing
      capability, favorable geometry, and optimized electrical properties. Herein, two
      novel imide-functionalized thiazoles, 5,5'-bithiazole-4,4'-dicarboxyimide (BTzI)
      and 2,2'-bithiazolothienyl-4,4',10,10'-tetracarboxydiimide (DTzTI), are
      successfully synthesized. Single crystal analysis and physicochemical study
      reveal that DTzTI is an excellent building block for constructing all-acceptor
      homopolymers, and the resulting polymer poly(2,2'-bithiazolothienyl-4,4',10,10'
      tetracarboxydiimide) (PDTzTI) exhibits unipolar n-type transport with a
      remarkable electron mobility (MUe ) of 1.61 cm2 V-1 s-1 , low off-currents (Ioff
      ) of 10-10 -10-11 A, and substantial current on/off ratios (Ion /Ioff ) of 107 
      108 in organic thin-film transistors. The all-acceptor homopolymer shows
      distinctive advantages over prevailing n-type donor-acceptor copolymers, which
      suffer from ambipolar transport with high Ioff s > 10-8 A and small Ion /Ioff s <
      105 . The results demonstrate that the all-acceptor approach is superior to the
      donor-acceptor one, which results in unipolar electron transport with more ideal
      transistor performance characteristics.

PMID- 29337390
TI  - Salt-dependent aquagenic urticaria in children: Report of two cases.

PMID- 29337392
TI  - Oral health-related concerns, behavior, and communication with health care
      providers of patients with breast cancer: impact of different treatments.
AB  - AIM: The objectives are to compare responses of breast cancer (BCa) treatment
      groups (chemotherapy, tamoxifen, and aromatase inhibitors (AIs) to each other and
      a control regarding (a) subjective oral health, (b) oral health-related
      behaviors, (c) oral health-related concerns, and (d) communication with health
      care providers. METHODS: Survey data were collected from 140 postmenopausal BCa
      patients and 41 healthy postmenopausal control respondents. RESULTS: BCa patients
      reported on average more frequent mouth sores/mucositis (5-point scale with 1 =
      never: 1.63 vs. 1.14; p < .01), glossadynia (1.60 vs. 1.07; p < .01), xerostomia
      (2.48 vs. 1.40; p < .01), and dysgeusia (2.10 vs. 1.46; p < .01) than the control
      respondents. Patients undergoing chemotherapy were more aware that cancer
      treatment can affect their oral health than patients on tamoxifen/AI (93% vs.
      55%/56%; p < .001). BCa patients reported being more frequently informed by
      oncologists about oral health-related effects of cancer treatment than by
      dentists. Oncologists/nurses were more likely to communicate about oral health
      related treatment effects with patients undergoing chemotherapy than patients on
      tamoxifen or AIs. Few BCa patients perceived dentists as knowledgeable about
      cancer treatment-related oral concerns and trusted them less than oncologists.
      CONCLUSIONS: BCa treatments impact oral health. Low percentages of BCa patients
      had received specific information about impacts of BCa treatments on oral health
      from their dentists.

PMID- 29337391
TI  - Time-dependent distinct roles of Toll-like receptor 4 in a house dust mite
      induced asthma mouse model.
AB  - House dust mites (HDMs) are a common source of allergens that trigger both
      allergen-specific and innate immune responses in humans. Here, we examined the
      effect of allergen concentration and the involvement of Toll-like receptor 4
      (TLR4) in the process of sensitization to house dust mite allergens in an HDM
      extract-induced asthma mouse model. Intranasal administration of HDM extract
      induced an immunoglobulin E response and eosinophilic inflammation in a dose
      dependent manner from 2.5 to 30 MUg/dose. In TLR4-knockout mice, the infiltration
      of eosinophils and neutrophils into the lung was decreased compared with that in
      wild-type mice in the early phase of inflammation (total of three doses).
      However, in the late phase of inflammation (total of seven doses), eosinophil
      infiltration was significantly greater in TLR4-knockout mice than in wild-type
      mice. This suggests that the roles of TLR4 signaling are different between the
      early phase and the later phase of HDM allergen-induced inflammation. Thus,
      innate immune response through TLR4 regulated the response to HDM allergens, and
      the regulation was altered during the phase of inflammation.

PMID- 29337393
TI  - Provision of information on dental implant treatment: Patients' thoughts and
      experiences.
AB  - OBJECTIVES: To explore patients' thoughts and perceptions of information
      provision regarding dental implant treatment. METHODS: This generic qualitative
      study involved 38 semi-structured face-to-face and telephone interviews with 34
      participants, who were at different stages of dental implant treatment. The
      interviews were transcribed verbatim. The data collection and coding process
      followed the principles of qualitative thematic analysis. RESULTS: Clinical
      sources of information were generally trusted by patients; however, patients
      clearly lacked information relative to their own specific situation, concerns and
      preferences, and this may lead to patients' reliance on other general sources of
      information. Crucial information on the long-term prosthesis needs was requested
      by patients at all treatment stages. Issues concerning the longevity and
      functional capability of the implant restoration and the long-term maintenance
      including optimisation of hygiene practice were questioned by patients and
      required greater explanation. CONCLUSION: With growing patient interest in
      implants for replacement of missing teeth, complete and accurate knowledge and
      understanding of implants should be established with patients. This should be
      undertaken with more reliance on reliable clinically based sources of implant
      information.

PMID- 29337394
TI  - 3D Printing of Materials with Tunable Failure via Bioinspired Mechanical
      Gradients.
AB  - Mechanical gradients are useful to reduce strain mismatches in heterogeneous
      materials and thus prevent premature failure of devices in a wide range of
      applications. While complex graded designs are a hallmark of biological
      materials, gradients in manmade materials are often limited to 1D profiles due to
      the lack of adequate fabrication tools. Here, a multimaterial 3D-printing
      platform is developed to fabricate elastomer gradients spanning three orders of
      magnitude in elastic modulus and used to investigate the role of various
      bioinspired gradient designs on the local and global mechanical behavior of
      synthetic materials. The digital image correlation data and finite element
      modeling indicate that gradients can be effectively used to manipulate the stress
      state and thus circumvent the weakening effect of defect-rich interfaces or
      program the failure behavior of heterogeneous materials. Implementing this
      concept in materials with bioinspired designs can potentially lead to defect
      tolerant structures and to materials whose tunable failure facilitates repair of
      biomedical implants, stretchable electronics, or soft robotics.

PMID- 29337395
TI  - Testosterone Suppression with Luteinizing Hormone-Releasing Hormone (LHRH)
      Agonists in Patients Receiving Radiotherapy for Prostate Cancer.
AB  - OBJECTIVES: To characterize the probability of testosterone escape during a
      course of radiotherapy and androgen deprivation (ADT) in patients with prostate
      cancer, and examine predictors of testosterone escape, the prostate specific
      antigen (PSA) levels during testosterone escape, and the impact of testosterone
      escape on outcome. PATIENTS AND METHODS: To participate in the database review,
      necessary data included: (i) type of luteinizing hormone-releasing hormone
      agonist (LHRHa) administered, date of initiation, and date of cessation or
      duration of therapy, (ii) radiotherapy information (start date and dose) with at
      least 6 months of follow-up after radiotherapy, (iii) radiotherapy to the
      prostate or prostate bed, and (iv) at least one serum testosterone and PSA
      measurement. RESULTS: Five hundred sixty patients in the database were identified
      as being treated with radiotherapy and ADT. Three hundred seventy-five patients
      had at least one measurement of testosterone and PSA, and the type of LHRHa used
      could be determined in 361 patients. Median follow-up of patients still living
      was 4.7 years. The median number of testosterone measurements per patient was
      six. The incidence of testosterone escape per patient course of treatment was
      buserelin, 9.3%; goserelin, 10.5%; intramuscular leuprolide, 11.5%; leuprolide
      subcutaneous, 23.9%; and triptorelin, 6.7% (p = 0.02). There was no difference in
      either biochemical failure-free survival or overall survival in patients
      stratified by testosterone escape. The modal PSA level during a testosterone
      escape was an undetectable PSA. CONCLUSIONS: An undetectable PSA does not rule
      out the presence of higher than desired levels of testosterone during ADT. In
      this cohort of patients, there appears to be no impact of testosterone escape on
      either biochemical relapse-free survival or overall survival.

PMID- 29337396
TI  - Aging and hypertension decrease endothelial NO-related dilating function and
      gamma-glutamyl transferase activity but not S-nitrosoglutathione-induced aortic
      vasodilation.
AB  - S-nitrosoglutathione (GSNO), which is involved in the transport and the storage
      of NO, induces vasorelaxation. It requires gamma-glutamyl transferase (GGT), an
      enzyme present on the endothelium, to transfer NO into the cell. We evaluated
      whether aging and hypertension, which induce NO-related dilating dysfunction, are
      associated with decreased vascular GGT activity and modify the vasorelaxant
      effect of GSNO. Thoracic aortic rings isolated from male spontaneous hypertensive
      rats (SHR) and Wistar-Kyoto rats (WKY) aged 20-22 (adult) or 57-60 weeks (mature)
      were preconstricted with phenylephrine, then submitted to concentration
      vasorelaxant response curves (maximal response: Emax ; pD2 ) to GSNO and
      carbachol (the latter to measure NO-related dilating function). GGT activity was
      measured using chromogenic substrate. Both aging and hypertension lowered Emax
      values for carbachol (Emax -8% in adult SHR, -42% in mature SHR vs. age-matched
      WKY, page and phypertension  < 0.05) demonstrating NO-related dilating
      dysfunction. Aortic GGT activity also decreased with aging and hypertension (-22%
      in adult and -75%, reaching 3 nmol/min/g of tissue, in mature SHR vs. 12 in age
      matched WKY and 23 in adult WKY, page and phypertension  < 0.05). The pD2 values
      of GSNO were similar in mature SHR and WKY but higher in adult SHR (pinteraction 
      < 0.05). Aging in hypertensive rats decreased NO-related vasorelaxant function
      and vascular GGT activity, but did not lower the vasorelaxant response to GSNO.
      This opens perspectives for GSNO-based therapeutics restoring nitric oxide
      bioavailability and vascular protection in a context of endothelial dysfunction.

PMID- 29337397
TI  - 2D PdAg Alloy Nanodendrites for Enhanced Ethanol Electroxidation.
AB  - The development of highly active and stable electrocatalysts for ethanol
      electroxidation is of decisive importance to the successful commercialization of
      direct ethanol fuel cells. Despite great efforts invested over the past decade,
      their progress has been notably slower than expected. In this work, the facile
      solution synthesis of 2D PdAg alloy nanodendrites as a high-performance
      electrocatalyst is reported for ethanol electroxidation. The reaction is carried
      out via the coreduction of Pd and Ag precursors in aqueous solution with the
      presence of octadecyltrimethylammonium chloride as the structural directing
      agent. Final products feature small thickness (5-7 nm) and random in-plane
      branching with enlarged surface areas and abundant undercoordinated sites. They
      exhibit enhanced electrocatalytic activity (large specific current ~2600 mA mgPd
      1) and excellent operation stability (as revealed from both the cycling and
      chronoamperometric tests) for ethanol electroxidation. Control experiments show
      that the improvement comes from the combined electronic and structural effects.

PMID- 29337398
TI  - Exploring knowledge, attitudes and experience of genitourinary symptoms in women
      with early breast cancer on adjuvant endocrine therapy.
AB  - Clinical trials of adjuvant endocrine therapy in women with early breast cancer
      have consistently reported that genitourinary symptoms are common. However,
      little is known about women's experiences of genitourinary symptoms, their views
      about the symptoms and how they impact on their lives. The aim of this study was
      to explore knowledge, attitudes and experiences of genitourinary symptoms among
      women receiving adjuvant endocrine therapy for early breast cancer. Thirty-two
      semi-structured interviews were conducted and subjected to a rigorous qualitative
      analysis. Genitourinary symptoms were commonly reported to negatively impact on
      personal, social and physical activities, were often attributed to anxiety and
      stress and were a source of embarrassment. Women also commented on the limited
      information available or provided regarding the potential genitourinary adverse
      effects of adjuvant endocrine therapy. There was a general lack of awareness that
      their symptoms could be associated with or exacerbated by adjuvant endocrine
      therapy. Women indicated a preference to receive information and advice about
      potential management options from either their general practitioner or
      specialist. These findings underscore the importance of improving communication
      and increasing awareness among both clinicians and patients about the potential
      impact of adjuvant endocrine therapy on genitourinary symptoms.

PMID- 29337399
TI  - Impact of pregnancy on psychoactive substance use among women with substance use
      disorders recruited in addiction specialized care centers in France.
AB  - Pregnancy can be a motivation for decrease in drug abusing but may also represent
      a period of high vulnerability for relapse. We aimed to assess psychoactive
      substance use among women with substance use disorders followed in addiction care
      centers in France. We analyzed data from women aged 15-44 years included in the
      'Observation of illegal drugs and misuse of psychotropic medication (OPPIDUM)
      survey', an annual cross-sectional survey collecting details on psychoactive
      substances used. Characteristics of women included in 2005-2012 yearly surveys
      were compared depending on their pregnant or not pregnant status. Factors,
      including pregnancy, associated with illicit substance use and medication misuse
      were investigated through logistic regression. The study included 518 pregnant
      and 6345 nonpregnant women; 85.3% pregnant women were on opioid maintenance
      therapy (OMT) (vs. 77.1% of nonpregnant). Pregnancy was associated with lower
      illicit substance use (adjusted OR 0.71 [0.58-0.88]) and with lower medication
      misuse (0.66 [0.49-0.89]), whereas financial insecurity and living as a couple
      were associated with increased risk. Raising children was significantly
      associated with less risk of substance use. Each substance taken separately, the
      part of women using illicit substance or misusing medication did not differ
      depending on whether they were pregnant or not, except for heroin (24.5% in
      pregnant vs. 17.9% nonpregnant; <0.001). This nationwide study provides new
      insights into psychoactive substance use in a large mixed population of women
      with drug use disorders. Results outline the challenge of preventing drug use and
      initiating care strategies with a specific approach on socio-economic
      environment.

PMID- 29337400
TI  - Immunization in end stage renal disease: The perception of waiting list patients.
AB  - BACKGROUND: The number of patients with chronic kidney disease is increasing
      worldwide, as well as the number of patients in kidney transplant waiting lists.
      In order to prevent infections related to immunosuppressive therapy, immunization
      guidelines for CKD patients before transplantation have been proposed. The aim of
      the present study was to evaluate adherence to immunization in a cohort of CKD
      patients in transplant waiting list and their renal replacement therapy clinics.
      METHODS: CKD patients older than 18 years old, receiving renal replacement
      therapy longer than 12 months and included in kidney transplant waiting list at
      University of Campinas (Unicamp) were enrolled. RESULTS: From February 2014 to
      December 2015, 105 patients fulfilled the inclusion criteria. Complete hepatitis
      B vaccination was observed in 73% and influenza vaccine in 67%. None of the other
      vaccine protocols reached 50% of coverage. Patients receiving immunization at
      primary health units presented higher coverage for diphtheria, tetanus (dT),
      measles, mumps, rubella (MMR), and hepatitis B vaccines, while patients immunized
      at renal replacement therapy clinics showed higher prevalence of pneumococcus
      (pneumo23). CONCLUSION: The low rates of immunization could reflect the RRT's
      clinics knowledge about the vaccines guidelines and its application on daily
      care. We suggest an integration between transplant center and RRT clinics,
      through lectures, periodic checking of vaccination cards, and easy to follow
      guidelines in order to provide a better vaccine coverage and to obtain higher
      immunization rates.

PMID- 29337402
TI  - Effect of length of dental resident clinical rotations on patient behavior.
AB  - AIM: The purpose of this retrospective chart review study was to determine if the
      length of residents' comprehensive dental care rotations in a general practice
      residency affected late cancellations, broken appointments, completion of
      treatment, timeliness of recall visits, emergency visits, and the need for redo
      of restorations and prostheses. METHODS: Patients who presented for comprehensive
      care from 2010 to 2013, during which residents had 3- to 4-month dental clinic
      rotations, comprised Group 1, and patients who presented for comprehensive care
      from 2013 to 2016, during which residents had 11-month dental clinic rotations,
      comprised Group 2. Subjects were excluded if they only presented for emergency
      care, they had only one visit, or their care was delivered in both time periods.
      There were 105 patients in Group 1 and 55 patients in Group 2. RESULTS: The
      statistically significant results were that Group 1 patients had more late
      cancellations and broken appointments and failed to reach recall status more
      often than Group 2 patients, and that Group 1 patients had fewer emergency
      visits. CONCLUSION: Within the limitations of this retrospective study, the
      results suggest that short block rotations have an adverse effect on resident
      experience and outcomes of patient care in a hospital outpatient setting.

PMID- 29337401
TI  - Rhabdomyolysis after co-administration of a statin and fusidic acid: an analysis
      of the literature and of the WHO database of adverse drug reactions.
AB  - Following a severe case of rhabdomyolysis in our University Hospital after a co
      administration of atorvastatin and fusidic acid, we describe this interaction as
      this combination is not clearly contraindicated in some countries, particularly
      for long-term treatment by fusidic acid. All cases of rhabdomyolysis during a co
      administration of a statin and fusidic acid were identified in the literature and
      in the World and Health Organization database, VigiBase(r) . In the literature,
      29 cases of rhabdomyolysis were identified; mean age was 66 years, median
      duration of co-administration before rhabdomyolysis occurrence was 21 days, 28%
      of cases were fatal. In the VigiBase(r) , 182 cases were retrieved; mean age was
      68 years, median duration of co-administration before rhabdomyolysis was 31 days
      and 24% of cases were fatal. Owing to the high fatality associated with this co
      administration and the long duration of treatment before rhabdomyolysis
      occurrence, fusidic acid should be used if there is no appropriate alternative,
      as long as statin therapy is interrupted for the duration of fusidic acid
      therapy, and perhaps a week longer. Rarely will interruption of this sort have
      adverse consequences for the patient.

PMID- 29337404
TI  - Mass trapping designs for organic control of the Japanese beetle, Popillia
      japonica (Coleoptera: Scarabaeidae).
AB  - BACKGROUND: In some regions of North America, damage caused by the Japanese
      beetle, Popillia japonica, has been increasing as beetle populations continue to
      become established and expand. This poses a pest management challenge for crop
      farmers, in particular organic producers. From 2014 to 2016 we evaluated the
      ability of novel mass trapping systems to capture P. japonica in elderberry and
      blueberry orchards in Missouri, USA. RESULTS: Across a 3-year period in two
      locations, the mass trapping systems collected 10.3 million P. japonica adults
      while season-long adult densities on crop plants were comparatively low
      (elderberry: 0.5-3.7 per plant; blueberry: 0.01-0.07 per plant). Damage by P.
      japonica averaged 6.8% per plant in elderberry and 0.12% in blueberry. In 2015
      and 2016, large-capacity bins with increased ventilation captured similar beetle
      numbers as did 1.2-m-long mesh socks (single design used in 2014), and these two
      trap designs outperformed non-ventilated bins. CONCLUSION: The mass trapping
      designs captured high numbers of adult P. japonica, while comparatively few
      adults and little damage to the foliage were recorded on plants. Mass trapping
      may provide effective alternative management options for P. japonica with less or
      no insecticides applied to the crop. (c) 2018 Society of Chemical Industry.

PMID- 29337405
TI  - Effects of transcutaneous electrical nerve stimulation on pain intensity during
      application of carboxytherapy in patients with cellulite: A randomized placebo
      controlled trial.
AB  - BACKGROUND: Carboxytherapy may generate local pain that is considered the main
      limiting factor in clinical practice. Transcutaneous electric nerve stimulation
      (TENS) is widely used in the control of acute pain; however, the effect of TENS
      on pain relief during carboxytherapy has not been studied to date. AIMS: To
      assess the effect of TENS on pain intensity during carboxytherapy in patients
      with cellulite in the gluteal region. PATIENTS/METHODS: This randomized clinical
      trial was conducted with 84 patients, 18-44 years of age, who had moderate
      cellulite in the gluteal region, according to Cellulite Severity Scale, but never
      received carboxytherapy. Patients were randomized into 3 groups: active TENS,
      placebo TENS, and control group. For the intervention, skin depressions with
      cellulite were outlined, and the gluteal area to be treated was defined. The
      subcutaneous injection of CO2 was performed using 0.30 * 13 mm-needles at a 45
      degrees  angle, with a controlled flow rate of 100 mL/min maintained for 1 minute
      at each puncture site. The parameters for TENS were as follows: frequency of 100
      Hz and pulse duration of 200 MUs; TENS intensity was adjusted until the patient
      reported strong paresthesia. The visual numeric pain rating scale was used to
      assess pain intensity after each puncture. RESULTS: The active TENS group
      reported lower pain intensity compared to the placebo TENS (P < .0001) and
      control (P < .0001) groups. CONCLUSIONS: Transcutaneous electric nerve
      stimulation (TENS) was effective in reducing pain intensity during carboxytherapy
      in patients with cellulite in the gluteal region.

PMID- 29337406
TI  - Validation of flow cytometric analysis of platelet function in patients with a
      suspected platelet function defect.
AB  - : Essentials The diagnosis of mild platelet function disorders (PFDs) is
      challenging. Validation of flow cytometric testing in patients with suspected
      PFDs is required. Flow cytometry has added value to light transmission
      aggregometry (LTA) in diagnosis of PFDs. There is fair agreement in diagnosing
      PFDs between LTA and flow cytometry. SUMMARY: Background Light transmission
      aggregometry (LTA) is the most commonly used test for the diagnosis of platelet
      function disorders (PFDs), but has moderate sensitivity for mild PFDs. Flow
      cytometry has been recommended for additional diagnostics of PFDs but is not yet
      standardized as a diagnostic test. We developed a standardized protocol for flow
      cytometric analysis of platelet function that measures fibrinogen binding and P
      selectin expression as platelet activation markers in response to agonist
      stimulation. Objectives To determine the additional value of flow cytometric
      platelet function testing to standard LTA screening in a cross-sectional cohort
      of patients with a suspected PFD. Methods Platelet function was assessed with
      flow cytometry and LTA in 107 patients suspected of a PFD in whom von Willebrand
      disease and coagulation factor deficiencies were excluded. Both tests were
      compared in terms of agreement and discriminative ability for diagnosing patients
      with PFDs. Results Out of 107 patients, 51 patients had an elevated bleeding
      score; 62.7% of the patients had abnormal platelet function measured with flow
      cytometry and 54.2% of the patients were abnormal based on LTA. There was fair
      agreement between LTA and flow cytometry (kappa = 0.32). The discriminative
      ability of flow cytometric analysis in patients with an elevated bleeding score
      was good (AUC 0.82, 0.74-0.90), but moderate for LTA (AUC 0.70, 0.60-0.80). Both
      tests combined had a better discriminative ability (AUC 0.87, 0.80-0.94).
      Conclusion Flow cytometric analysis of platelet function has added value in
      diagnostics of PFDs in patients with unexplained bleeding tendency.

PMID- 29337407
TI  - Insufficient sleep syndrome: An unrecognized but important clinical entity.
AB  - BACKGROUND: A sleep clinic for adults and children was established in the Tokyo
      Bay Urayasu Ichikawa Medical Centre, in August 2012. Given that few sleep clinics
      are available in Japan specifically for children, this clinic provides the
      opportunity to provide data on child patients with sleep problems. METHODS:
      Records of patients who visited the sleep clinic at the Tokyo Bay Urayasu
      Ichikawa Medical Centre aged <=20 years at the first visit were retrospectively
      examined, along with the initial and final diagnoses. RESULTS: Of 2,157 patients
      who visited the sleep clinic at Tokyo Bay Urayasu Ichikawa Medical Centre between
      August 2012 and March 2017, 181 were <=20 years old. In these 181 patients, the
      most frequent final diagnosis was insufficient sleep syndrome (ISS), n = 56,
      followed by circadian rhythm sleep-wake disorder, n = 28; insomnia, n = 28; and
      sleep-related movement disorder, n = 15. CONCLUSIONS: Insufficient sleep produces
      various brain dysfunctions in both adults and children, and is associated with
      behavioral, cognitive and physical problems, as well as with atypical early
      development. Insufficient sleep has also been reported to cause obesity.
      Insufficient sleep-induced obesity is often associated with the occurrence of
      metabolic syndrome. More effort is needed to ensure that children are receiving
      sufficient sleep.

PMID- 29337408
TI  - Maternally expressed miR-379/miR-544 cluster is dispensable for testicular
      development and spermatogenesis in mice.

PMID- 29337409
TI  - Engineering of 'Purple Embryo Maize' with a multigene expression system derived
      from a bidirectional promoter and self-cleaving 2A peptides.

PMID- 29337410
TI  - Transcriptomic insight into pathogenicity-associated factors of Conidiobolus
      obscurus, an obligate aphid-pathogenic fungus belonging to Entomopthoromycota.
AB  - BACKGROUND: Conidiobolus obscurus is a widespread fungal entomopathogen with
      aphid biocontrol potential. This study focused on a de novo transcriptomic
      analysis of C. obscurus. RESULTS: A number of pathogenicity-associated factors
      were annotated for the first time from the assembled 17 231 fungal unigenes,
      including those encoding subtilisin-like proteolytic enzymes (Pr1s), trypsin-like
      proteases, metalloproteases, carboxypeptidases and endochitinases. Many of these
      genes were transcriptionally up-regulated by at least twofold in mycotized
      cadavers compared with the in vitro fungal cultures. The resultant transcriptomic
      database was validated by the transcript levels of three selected pathogenicity
      related genes quantified from different in vivo and in vitro material in real
      time quantitative polymerase chain reaction (PCR). The involvement of multiple
      Pr1 proteases in the first stage of fungal infection was also suggested.
      Interestingly, a unique cytolytic (Cyt)-like delta-endotoxin gene was highly
      expressed in both mycotized cadavers and fungal cultures, and was more or less
      distinct from its homologues in bacteria and other fungi. CONCLUSION: Our
      findings provide the first global insight into various pathogenicity-related
      genes in this obligate aphid pathogen and may help to develop novel biocontrol
      strategy against aphid pests. (c) 2018 Society of Chemical Industry.

PMID- 29337411
TI  - The Fourth Wave of Biocatalysis Emerges- The 13 th International Symposium on
      Biocatalysis and Biotransformations.
AB  - Ride the wave! Biocatalysis uses nature's catalysts, enzymes and whole cell
      systems, for synthetic purposes. In a biotransformation, the biocatalyst
      transforms a well-defined substrate to the desired product, in contrast to the
      fermentation process, which produces the desired product from a complex mixture
      of nutrients. Biocatalysis has reached an industrially established level through
      several waves of technological evolution; participants of the BioTrans 2017
      conference in Budapest could witness the newest wave of this technology.

PMID- 29337412
TI  - Metallic Nanodot Patterns with Unique Symmetries Templated from ABC Triblock
      Terpolymer Networks.
AB  - Nanotemplates derived from the self-assembly of AB-type block copolymers provide
      an elegant route to achieve well-defined metallic dot arrays, even if the variety
      of pattern symmetries is restricted due to the limited number of structures
      offered by microphase separated diblock copolymers. A strategy that relies on the
      use of complex network structures accessible through the self-assembly of linear
      ABC-type terpolymers is presented for the formation of metallic nanodots arrays
      with "outside-the-box" symmetries. Patterned templates formed by the cubic Q214
      and orthorhombic O70 network structures are used as excellent platforms to build
      well-ordered gold nanodot arrays with unique p3m1 and p2 symmetries,
      respectively. A simple yet efficient blending strategy is used to tune the
      critical dimensions of the p3m1 pattern while laterally ordered gold nanodot
      arrays are also demonstrated through a directed self-assembly approach. Such
      highly ordered gold nanodots with tunable particle dimensions and array periods,
      enabling the control of their plasmonic responses, are attractive probes for
      biological imaging.

PMID- 29337413
TI  - Participation of relatives in the care of cancer patients in hospital-A scoping
      review.
AB  - The purpose of the review was to describe what kind of research has been
      conducted concerning relatives' participation in the care of cancer patients in
      hospital and how relatives have participated in the care. Data (n = 9) were
      identified through a manual search and by searching the electronic databases (n =
      8) Cinahl, PubMed and Cochrane Library and analysed with deductive content
      analysis. According to the review, participation in the concrete care appeared as
      taking care of comprehensive care and the quality of care, helping with daily
      activities and helping the healthcare professionals. Emotional support appeared
      as protecting, supporting and visiting the patient and discussing with the
      patient. Participation in decision-making appeared as acting as an advocate for
      the patient, participating in the discussion concerning the decision-making and
      participating in the discussion concerning the decisions of end of life.
      According to the review, research concerning this topic seems to be rare. While
      hospital periods are shortening and homecare is increasing, the role of relatives
      as a supporter of the cancer patient is becoming even stronger. In the future,
      more research should be conducted how the patients experience participation and
      what are their wishes.

PMID- 29337414
TI  - Proliferative leukoplakia: Proposed new clinical diagnostic criteria.
AB  - OBJECTIVE: We aimed to characterize proliferative verrucous leukoplakia (PVL)
      from a clinical and histopathological standpoint and suggest an updated
      classification. SUBJECTS AND METHODS: Records of patients seen at three oral
      medicine centers with a clinical diagnosis of PVL were reviewed for clinical and
      histopathological features and malignant transformation (MT). RESULTS: There were
      42 patients (median age: 69 years [range: 36-88]; 35 females). 12.2% were current
      smokers. Family history of cancer was present in 43.7% of patients. Partial
      demarcation of lesion margins was present in 31.3% of lesions, followed by
      verrucous (27.5%), smooth (22.7%) erythematous (22.3%), and fissured (18.3%)
      appearance. Large and contiguous and multisite and non-contiguous lesions
      comprised 57.1% (24/42) and 35.7% (15/42) of PVL cases, respectively. 19.1% had
      prominent erythema (erythroleukoplakia). The most common histopathological
      diagnosis at first visit was hyperkeratosis without dysplasia (22/42; 56.4%). MT
      occurred in 71.4% patients after a median of 37 months [range: 1-210] from
      initial visit; erythroleukoplakia exhibited MT in 100% of cases. CONCLUSION: The
      generic term "proliferative leukoplakia (PL)" may be more appropriate than PVL
      because 18.3% were fissured and 22.7% erythematous. We also propose the term
      proliferative erythroleukoplakia to more accurately describe the subset of PL
      with prominent erythema, which had the highest MT rate.

PMID- 29337415
TI  - Self-Healing in Supramolecular Polymers.
AB  - Adaption and self-healing are two major principles in material science, often
      coupled with the placement of supramolecular moieties within a material. Proper
      molecular design can enable self-healing within such materials, displaying
      enormous potential in technology and application. Here, basic physicochemical
      aspects as well as new material developments in the field are described,
      published after a recent review in Macromolecular Rapid Communications in 2013.

PMID- 29337416
TI  - The role of ADAMTS-13 in the coagulopathy of sepsis.
AB  - The interaction between platelets and the vessel wall is mediated by various
      receptors and adhesive proteins, of which von Willebrand factor (VWF) is the most
      prominent. The multimeric size of VWF is an important determinant of a more
      intense platelet-vessel wall interaction, and is regulated by the VWF-cleaving
      protease ADAMTS-13. A deficiency in ADAMTS-13 leads to higher concentrations of
      ultralarge VWF multimers and pathological platelet-vessel wall interactions, in
      its most typical and extreme form leading to thrombocytopenic thrombotic purpura,
      a thrombotic microangiopathy characterized by thrombocytopenia, non-immune
      hemolysis, and organ dysfunction. Thrombotic microangiopathy associated with low
      levels of ADAMTS-13 may be a component of the coagulopathy observed in patients
      with sepsis. Here, we review the potential role of ADAMTS-13 deficiency and
      ultralarge VWF multimers in sepsis, and their relationship with sepsis severity
      and prognosis. In addition, we discuss the possible benefit of restoring ADAMTS
      13 levels or reducing the effect of ultralarge VWF as an adjunctive treatment in
      patients with sepsis.

PMID- 29337417
TI  - Guillain-Barre syndrome in a local area in Japan, 2006-2015: an epidemiological
      and clinical study of 108 patients.
AB  - BACKGROUND AND PURPOSE: Many epidemiological studies of Guillain-Barre syndrome
      (GBS) and Fisher syndrome (FS) have been conducted in Europe and America. In
      contrast, epidemiological studies are rare in Asia where the GBS subtypes differ
      from those in Western countries. This study was undertaken to clarify the
      incidence of GBS and FS in a local area in Japan as well as their seasonal
      trends. METHOD: Seventy-one GBS and 37 FS patients were recorded from 2006 to
      2015 in an area of approximately 1.5 million inhabitants in Japan. The incidence,
      seasonal trends and clinical features of GBS and FS were examined. RESULTS: The
      incidence rate of GBS was 0.42 cases per 100 000 person-years and that of FS was
      0.22 cases per 100 000 person-years. The incidence of GBS increased with age and
      FS affected predominantly patients aged from 45 to 64 years old. There was some
      seasonal clustering of acute motor axonal neuropathy (AMAN) and FS in spring and
      summer, but it was not significant. AMAN and FS patients had a high frequency of
      preceding infection (AMAN, 68% gastrointestinal infection; FS, 65% upper
      respiratory infection). Antecedent respiratory infection was significantly
      associated with FS as an outcome. Serum antibodies to ganglioside GM1 were
      detected in 71% of AMAN patients and antibodies to GQ1b were detected in 81% of
      FS patients. CONCLUSIONS: Our study offers evidence of a lower incidence of GBS
      and a higher incidence of FS in a local area in Japan than in Western countries.

PMID- 29337418
TI  - Specific Noncovalent Interactions Determine Optimal Structure of a Buried Ligand
      Moiety: QM/MM and Pure QM Modeling of Complexes of the Small-Molecule CD4
      Mimetics and HIV-1 gp120.
AB  - The small-molecule CD4 mimetics (smCD4mcs) are a class of highly potent HIV-1
      entry inhibitors characterized by a unique structure-activity relationship (SAR).
      They share a halogenated phenyl ring (region 1) that deeply inserts into an
      otherwise water-filled cavity at the CD4 binding site on the gp120 surface, the
      so-called F43 cavity. Conservative modifications to region 1 away from this
      halogenated phenyl motif have all led to loss of activity, despite the fact that
      they are predicted by standard empirical computational approaches to bind equally
      well, making it difficult to further optimize this region of the compounds to
      increase binding to gp120. In this study we used quantum mechanical methods to
      understand the roots of the interactions between region 1 and the F43 cavity. We
      clearly demonstrate the presence of halogen bond/sigma-hole and dispersion
      interactions between region 1 and the F43 cavity residues F376-N377, which are
      not captured by standard molecular mechanics approaches and the role played by
      the smCD4mc in the F43 cavity desolvation. These findings rationalize why the
      halogenated region 1 has proven so difficult to move beyond in smCD4mc
      optimization, in agreement with experimental evidence.

PMID- 29337419
TI  - Evolution of resistance to chytridiomycosis is associated with a robust early
      immune response.
AB  - Potentiating the evolution of immunity is a promising strategy for addressing
      biodiversity diseases. Assisted selection for infection resistance may enable the
      recovery and persistence of amphibians threatened by chytridiomycosis, a
      devastating fungal skin disease threatening hundreds of species globally.
      However, knowledge of the mechanisms involved in the natural evolution of
      immunity to chytridiomycosis is limited. Understanding the mechanisms of such
      resistance may help speed-assisted selection. Using a transcriptomics approach,
      we examined gene expression responses of endangered alpine tree frogs (Litoria
      verreauxii alpina) to subclinical infection, comparing two long-exposed
      populations with a naive population. We performed a blinded, randomized and
      controlled exposure experiment, collecting skin, liver and spleen tissues at 4, 8
      and 14 days postexposure from 51 wild-caught captively reared infection-naive
      adult frogs for transcriptome assembly and differential gene expression analyses.
      We analysed our results in conjunction with infection intensity data, and the
      results of a large clinical survival experiment run concurrently with individuals
      from the same clutches. Here, we show that frogs from an evolutionarily long
      exposed and phenotypically more resistant population of the highly susceptible
      alpine tree frog demonstrate a more robust innate and adaptive immune response at
      the critical early subclinical stage of infection when compared with two more
      susceptible populations. These results are consistent with the occurrence of
      evolution of resistance against chytridiomycosis, help to explain underlying
      resistance mechanisms, and provide genes of potential interest and sequence data
      for future research. We recommend further investigation of cell-mediated immunity
      pathways, the role of interferons and mechanisms of lymphocyte suppression.

PMID- 29337420
TI  - A proinflammatory response of bovine endometrial epithelial cells to active sperm
      in vitro.
AB  - In the cow, cryopreserved semen is inseminated into the uterus, and most of sperm
      are removed by backflow and phagocytes. Nevertheless, the mechanism responsible
      for sperm phagocytosis is unclear. Here, we used cultured bovine uterine
      epithelial cells (BUECs) to investigate the uterine response to sperm and the
      mechanism that activates polymorphonuclear neutrophils (PMNs). BUEC monolayers
      were co-cultured with different numbers of washed sperm obtained from
      cryopreserved semen (104 , 105 , and 106 sperm/ml) for 3 hr. Sperm dose
      dependently up-regulated IL8 (Interleukin 8). Sperm at 106 /ml increased mRNA
      expression of TNFA (Tumor necrosis factor alpha), IL1B (Interleukin 1B), NFKB2
      (Nuclear factor kappa B2), and C3 (Complement factor 3), as well as PGES
      (Prostaglandin E synthase) expression and PGE2 release. Live sperm, but not dead
      sperm, attached to BUECs, and dead sperm did not induce an acute inflammatory
      response. Time-dependent effects were evaluated by co-culture of 106 /ml washed
      sperm with BUECs for 0, 1, 3, and 6 hr. The number of detached sperm increased
      gradually toward 6 hr. Maximum mRNA expression of IL8, TNFA, IL1B, and NFKB2 was
      induced at 3 hr, while C3 continued to increase toward 6 hr. Sperm did not
      stimulate mRNA expression of anti-inflammatory cytokines TGFB1 (Transforming
      growth factor beta 1) or IL10 (Interleukin 10). Medium conditioned by sperm co
      incubated with BUECs stimulated PMNs phagocytosis of sperm in vitro. Fresh media
      supplemented with low levels of IL1B, TNFA, and PGE2 up-regulated sperm
      phagocytosis by PMNs as well. In conclusion, our findings strongly suggest that
      the active sperm attach to BUECs and trigger uterine local innate immunity with
      induction of a pro-inflammatory response that enhances sperm phagocytosis by
      PMNs.

PMID- 29337421
TI  - Fenoxaprop-P-ethyl resistance conferred by cytochrome P450s and target site
      mutation in Alopecurus japonicus.
AB  - BACKGROUND: Alopecurus japonicus is a serious grass weed species in wheat fields
      in eastern Asia, and has evolved strong resistance to acetyl-CoA carboxylase
      (ACCase)-inhibiting herbicides. Although target-site resistance (TSR) to ACCase
      inhibitors in A. japonicus has been reported, non-target site resistance (NTSR)
      has not. This study investigated both TSR and NTSR in a fenoxaprop-P-ethyl
      resistant A. japonicus population (AHFD-3), which was collected in Feidong
      County, Anhui Province, China. RESULTS: We found that AHFD-3 exhibited high
      resistance to fenoxaprop-P-ethyl and low resistance to flucarbazone-sodium. The
      sensitivity of AHFD-3 to fenoxaprop-P-ethyl increased significantly after
      treatment with cytochrome P450 (P450) inhibitors; however, such synergies between
      P450 inhibitors and fenoxaprop-P-ethyl were not found in two control populations.
      Sequences of the entire carboxyltransferase domain of A. japonicus ACCase were
      obtained, and AHFD-3 plants showed an Asp-2078-Gly substitution in the ACCase.
      With the derived cleaved amplified polymorphic sequence (dCAPS) method, we found
      that 85.4% of the plants of AHFD-3 carried this mutation. The P450 content in
      AHFD-3 plants was significantly higher than those of the two control populations
      after treatment with fenoxaprop-P-ethyl. Ten partial sequences of P450 genes in
      A. japonicus were cloned. Three P450 genes were up-regulated 12 h after
      fenoxaprop-P-ethyl treatment, which were all from the P450 subfamily CYP72A.
      Moreover, a P450 gene from the P450 family CYP81 was up-regulated after
      fenoxaprop-P-ethyl treatment in all populations studied. CONCLUSION: Fenoxaprop-P
      ethyl resistance in AHFD-3 plants was conferred by up-regulation of cytochrome
      P450s in the CYP72A subfamily and target site mutation of the ACCase gene. (c)
      2018 Society of Chemical Industry.

PMID- 29337422
TI  - Hollow Mesoporous Silica@Metal-Organic Framework and Applications for pH
      Responsive Drug Delivery.
AB  - Metal--organic frameworks (MOFs), a new type of porous crystalline material, hold
      great potential in biomedical applications, such as drug delivery. However, the
      efficacy of drug delivery is limited by low drug loading. In this work, we
      synthesized hollow mesoporous silica (HMS)@MOF capsules that can be used as a pH
      responsive drug delivery system for the anticancer drug doxorubicin (DOX). DOX is
      loaded into the inner cavity of HMS. Zeolitic imidazolate framework-8 (ZIF-8)
      nanoparticles are then coated on the outer surface of the DOX-loaded HMS. The
      obtained material is a capsule (denoted as DOX/HMS@ZIF), in which DOX is
      encapsulated. The DOX/HMS@ZIF can be used as an efficient pH-responsive drug
      delivery system. DOX is not released under physiological conditions (pH 7.4), but
      is released at low pH (4-6) from DOX/HMS@ZIF. The DOX/HMS@ZIF capsule shows much
      higher cytotoxicity than free DOX and alters the delivery pathway for DOX in
      cancer cells, while the drug-free HMS@ZIF shows excellent biocompatibility. This
      opens new opportunities to construct a safe and efficient delivery system for
      targeted molecules using pH-responsive release for a wide range of applications.

PMID- 29337423
TI  - The next generation of melanocyte data: Genetic, epigenetic, and transcriptional
      resource datasets and analysis tools.
AB  - The number of melanocyte- and melanoma-derived next generation sequence genome
      scale datasets have rapidly expanded over the past several years. This resource
      guide provides a summary of publicly available sources of melanocyte cell derived
      whole genome, exome, mRNA and miRNA transcriptome, chromatin accessibility and
      epigenetic datasets. Also highlighted are bioinformatic resources and tools for
      visualization and data queries which allow researchers a genome-scale view of the
      melanocyte.

PMID- 29337424
TI  - Enantiomeric separation of six chiral pesticides that contain chiral
      sulfur/phosphorus atoms by supercritical fluid chromatography.
AB  - Six chiral pesticides containing chiral sulfur/phosphorus atoms were separated by
      supercritical fluid chromatography with supercritical CO2 as the main mobile
      phase component. The effect of the chiral stationary phase, different type and
      concentration of modifiers, column temperature, and backpressure on the
      separation efficiency was investigated to obtain the appropriate separation
      condition. Five chiral pesticides (isofenphos-methyl, isocarbophos, flufiprole,
      fipronil, and ethiprole) were baseline separated under experimental conditions,
      while isofenphos only obtained partial separation. The Chiralpak AD-3 column
      showed a better chiral separation ability than others for chiral pesticides
      containing chiral sulfur/phosphorus atoms. When different modifiers at the same
      concentration were used, the retention factor of pesticides except flufiprole
      decreased in the order of isopropanol, ethanol, methanol; meanwhile, the
      retention factor of flufiprole increased in the order of isopropanol, ethanol,
      methanol. For a given modifier, the retention factor and resolution decreased on
      the whole with the increase of its concentration. The enantiomer separation of
      five chiral pesticides was an "enthalpy-driven" process, and the separation
      factor decreased as the temperature increased. The backpressure of the mobile
      phase had little effect on the separation factor and resolution.

PMID- 29337425
TI  - Distinct gene expression profiles and regulation networks of nasal polyps in
      eosinophilic and non-eosinophilic chronic rhinosinusitis.
AB  - BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is known to have 2
      phenotypes in East Asia. Eosinophilic CRSwNP (ECRSwNP), defined as tissue
      eosinophilia and easily recurrent, is distinguished from other non-eosinophilic
      CRSwNP (NECRSwNP) types. However, the pathogenesis of each remains unclear.
      METHODS: Nasal polyp tissues from ECRS (ECRSwNP) and NECRS (NECRSwNP) patients
      were obtained, and their comprehensive gene expression profiles were investigated
      by microarray analysis. Bioinformatics approaches (eg, Ingenuity Pathway Analysis
      [IPA]) were used to interrogate the data sets. RESULTS: Hierarchical clustering
      and principal component analysis (PCA) collectively showed that ECRSwNP and
      NECRSwNP had distinct gene expression patterns. Of note, these genes could be
      divided into 8 distinctive clusters having different expression patterns and
      functions. Upstream Regulator Analysis revealed that not only T-helper 2 (Th2)
      and the eosinophilia-related molecules (interleukin 4 [IL4], IL5, and colony
      stimulating factor 2 [CSF2]) reported so far, but also cell cycle regulators
      (cyclin dependent kinase inhibitor 1A [CDKNA1] and cyclin D1 [CCND1]) and a
      tissue fibrosis-related molecule (transforming growth factor beta [TGFbeta]) were
      identified in ECRSwNP. On the other hand, mainly interferons (IFNs) and acute
      inflammatory cytokines (IL1 and IL6) were predicted as upstream regulators in
      NECRSwNP. CONCLUSION: These results are useful for understanding the molecular
      basis of the mechanisms of CRSwNP and point to new targets for developing
      specific biomarkers and personalized therapeutic strategies for CRSwNP.

PMID- 29337426
TI  - Prospective randomized study of conversion from tacrolimus to cyclosporine A to
      improve glucose metabolism in patients with posttransplant diabetes mellitus
      after renal transplantation.
AB  - Tacrolimus (TAC) increases the risk of posttransplant diabetes (PTDM) compared
      with cyclosporine A (CYC). The present 12-month, multicenter, investigator
      driven, prospective, randomized study was designed to assess whether conversion
      from tacrolimus to CYC can reverse PTDM after renal transplantation.
      Predominantly white patients with PTDM according to the 2005 American Diabetes
      Association criteria were randomized to either replacement of TAC with CYC or
      continuation of their TAC-based regimen after stratification for type of glucose
      lowering therapy, steroid therapy, and hepatitis C status. At 12 months, 14 of 41
      patients with complete data in the CYC arm (34%; 95%CI 19%-49%) were free of
      diabetes, whereas this was the case in only 4 of 39 patients (10%; 95%CI 3%-20%)
      in the TAC arm (P = .01). At 12 months, 39% of patients in the CYC arm were off
      glucose-lowering medication vs 13% of patients in the TAC arm (P = .01). The CYC
      group decreased glycated hemoglobin level during the 12-month follow-up,
      resulting in significantly lower levels compared with the TAC group (6.0 +/- 0.9%
      vs 7.1 +/- 1.7% at 12 months; P = .002). In conclusion, replacement of TAC with
      CYC significantly improves glucose metabolism and has the potential to reverse
      diabetes during the first year after conversion. (EU Clinical Trials Register No.
      2006-001765-42).

PMID- 29337427
TI  - Outcomes From the First Helene Fuld Health Trust National Institute for Evidence
      Based Practice in Nursing and Healthcare Invitational Expert Forum.
AB  - BACKGROUND: Even though multiple positive outcomes are the result of evidence
      based care, including improvements in healthcare quality, safety, and costs, it
      is not consistently delivered by clinicians in healthcare systems throughout the
      world. AIMS: In an attempt to accelerate the implementation of evidence-based
      practice (EBP) across the United States, an invitational Interprofessional
      National EBP Forum to determine major priorities for the advancement of EBP was
      held during the launch of the newly established Helene Fuld Health Trust National
      Institute for Evidence-Based Practice in Nursing and Healthcare at The Ohio State
      University College of Nursing. METHODS: Interprofessional leaders from national
      organizations and federal agencies across the United States were invited to
      participate in the Forum. A pre-Forum survey was disseminated to participants to
      assess their perceptions of the state of EBP and actions necessary to speed the
      translation of research into real-world clinical settings. RESULTS: Findings from
      a pre-Forum survey (n = 47) indicated ongoing low implementation of EBP in U.S.
      healthcare settings. These findings were shared with leaders from 45
      organizations and agencies who attended the Forum. Breakout groups on practice,
      education, implementation science, and policy discussed the findings and
      responded to a set of standardized questions. High-priority action tactics were
      identified, including the need for: (a) enhanced reimbursement for EBP, (b) more
      interprofessional education and skills building in EBP, and (c) leaders to
      prioritize EBP and fuel it with resources. LINKING EVIDENCE TO ACTION: The
      delivery of and reimbursement for evidence-based care must become a high national
      priority. Academic faculty across all healthcare disciplines need to teach EBP,
      healthcare systems must invest in EBP resources, and payers must attach
      reimbursement to care that is evidence-based. An action collaborative of the
      participating organizations has been formed to accelerate EBP across the United
      States to achieve the quadruple aim in health care.

PMID- 29337428
TI  - AP4 positively regulates LAPTM4B to promote hepatocellular carcinoma growth and
      metastasis, while reducing chemotherapy sensitivity.
AB  - Polymorphisms of the lysosomal-associated protein transmembrane-4 beta (LAPTM4B)
      gene are related to various forms of tumour susceptibility, which led us to
      hypothesize that some unique transcription factors targeting this polymorphism
      region may affect the biological function of LAPTM4B in tumour progression. In
      this study, we found that the transcription factor AP4 directly binds to the
      polymorphism region of the LAPTM4B gene promoter and induces its transcription.
      In addition, we demonstrated that AP4 promotes hepatocellular carcinoma (HCC)
      cell proliferation and metastasis and depresses chemotherapy sensitivity via
      LAPTM4B by activating the PI3K/AKT signalling pathway and caspase-dependent
      pathway. Interestingly, we found that AP4 could not only regulate LAPTM4B by
      directly binding to the promoter, but also be regulated via a positive feedback
      mechanism involving LAPTM4B acting on c-myc. Finally, we showed that AP4 and
      LAPTM4B are highly coexpressed in HCC tissues, and their coexpression may be a
      marker of poor prognosis. These findings provide evidence of the expression and
      functional coupling between AP4 and LAPTM4B and shed light on the regulation of
      LAPTM4B and its function in liver cancer.

PMID- 29337429
TI  - Co-Expression of ORFCma with PHB Depolymerase (PhaZCma ) in Escherichia coli
      Induces Efficient Whole-Cell Biodegradation of Polyesters.
AB  - Whole-cell degradation of polyesters not only avoids the tedious process of
      enzyme separation, but also allows the degraded product to be reused as a carbon
      source. In this study, Escherichia coli BL21(DE3) harboring phaZCma , a gene
      encoding poly(3-hydroxybutyrate) (PHB) depolymerase from Caldimonas
      manganoxidans, is constructed. The extra-cellular fraction of E. coli/pPHAZ
      exhibits a fast PHB degradation rate where it only took 35 h to completely
      degrade PHB films, while C. manganoxidans takes 81 h to do the same. The co
      expression of ORFCma (a putative periplasmic substrate binding protein that is
      within the same operon of phaZCma ) further improves the PHB degradation. While
      28 h is needed for E. coli/pPHAZ to cause an 80% weight loss in PHB films, E.
      coli/pORFPHAZ needs only 21 h. Furthermore, it is able to degrade at-least four
      different polyesters, PHB, poly(lactic acid) (PLA), polycaprolactone (PCL), and
      poly(butylene succinate-co-adipate) (PBSA). Testing of the time course of 3
      hydroxybutyrate concentration and the turbidity of the degradation solutions over
      time shows that PhaZCma has both exo- and endo-enzymatic activity. The whole-cell
      E. coli/pORFPHAZ can be used for recycling various polyesters while ORFCma can
      potentially be a universal element for enhancing the secretion of recombinant
      protein.

PMID- 29337431
TI  - Spotlights on our sister journals: Angew. Chem. Int. Ed. 4/2018.

PMID- 29337430
TI  - Corrigendum: Interband Absorption Enhanced Optical Activity in Discrete Au@Ag
      Core-Shell Nanocuboids: Probing Extended Helical Conformation of Chemisorbed
      Cysteine Molecules.

PMID- 29337432
TI  - Corrigendum: Nanoscale Control of Homoepitaxial Growth on a Two-Dimensional
      Zeolite.

PMID- 29337433
TI  - Numerical simulation of two consecutive nasal respiratory cycles: toward a better
      understanding of nasal physiology.
AB  - BACKGROUND: Computational fluid dynamic (CFD) simulations have greatly improved
      the understanding of nasal physiology. We postulate that simulating the entire
      and repeated respiratory nasal cycles, within the whole sinonasal cavities, is
      mandatory to gather more accurate observations and better understand airflow
      patterns. METHODS: A 3-dimensional (3D) sinonasal model was constructed from a
      healthy adult computed tomography (CT) scan which discretized in 6.6 million
      cells (mean volume, 0.008 mm3 ). CFD simulations were performed with
      ANSYS(c)FluentTMv16.0.0 software with transient and turbulent airflow (k-omega
      model). Two respiratory cycles (8 seconds) were simulated to assess pressure,
      velocity, wall shear stress, and particle residence time. RESULTS: The pressure
      gradients within the sinus cavities varied according to their place of connection
      to the main passage. Alternations in pressure gradients induced a slight pumping
      phenomenon close to the ostia but no movement of air was observed within the
      sinus cavities. Strong movements were observed within the inferior meatus during
      expiration contrary to the inspiration, as in the olfactory cleft at the same
      time. Particle residence time was longer during expiration than inspiration due
      to nasal valve resistance, as if the expiratory phase was preparing the next
      inspiratory phase. Throughout expiration, some particles remained in contact with
      the lower turbinates. The posterior part of the olfactory cleft was gradually
      filled with particles that did not leave the nose at the next respiratory cycle.
      This pattern increased as the respiratory cycle was repeated. CONCLUSION: CFD is
      more efficient and reliable when the entire respiratory cycle is simulated and
      repeated to avoid losing information.

PMID- 29337434
TI  - Light and darkness in circadian rhythms.

PMID- 29337435
TI  - Hyalinosis cutis et mucosae: A clinical investigation with special regard to
      mucosal changes.

PMID- 29337436
TI  - Integrating TEMPO and Its Analogues with Visible-Light Photocatalysis.
AB  - Visible light has risen to become a very important facilitator for selective
      radical reactions enabled by well-cognized photocatalysts. The renaissance of
      visible-light photocatalysis on this matter partly relies on integrating it with
      other fields of catalysis. In parallel, 2,2,6,6-tetramethylpiperidin N-oxide
      (TEMPO), a quintessential persistent radical, has a wide range of uses owing to
      its exceptional redox behavior, which gives rise to its latest prominence in
      catalysis. Therefore, integrating the catalysis of TEMPO with photocatalysis to
      perform visible-light-induced selective reactions becomes a very convenient
      marriage of merits. In this context, the integration of different types of
      photocatalysts, including metal complexes, metal-free organic dyes, and
      semiconductors, with TEMPO for outstanding organic transformations will be
      summarized. To expand further the catalytic repertoire, the integration of TEMPOH
      analogues such as NHPI (N-hydroxyphthalimide) and NHS (N-hydroxysuccinimide) with
      photocatalysis will also be discussed. Hopefully, these advances will pave the
      way for more breakthroughs by integrating TEMPO and its analogues with
      photocatalysis to lead to a valuable blueprint for visible-light-induced
      selective organic transformations.

PMID- 29337437
TI  - Canonical signaling and nuclear activity of mTOR-a teamwork effort to regulate
      metabolism and cell growth.
AB  - Mechanistic (or mammalian) target of rapamycin (mTOR) is a kinase that regulates
      almost all functions related to cell growth and metabolism in response to extra-
      and intracellular stimuli, such as availability of nutrients, the presence of
      growth factors, or the energy status of the cell. As part of two distinct protein
      complexes, mTORC1 and mTORC2, the kinase has been shown to influence cell growth
      and proliferation by controlling ribosome biogenesis, mRNA translation,
      carbohydrate and lipid metabolism, protein degradation, autophagy as well as
      microtubule and actin dynamics. In addition to these well-characterized
      functions, mTOR can also influence gene transcription. While most studies focused
      on investigating how canonical mTOR signaling regulates the activity of
      transcription factors outside the nucleus, recent findings point to a more direct
      role for mTOR as a transcription factor operating on chromatin in the nucleus. In
      particular, recent genome-wide identification of mTOR targets on chromatin
      reveals that its activities in the nucleus and cytoplasm are functionally and
      biologically linked, thus uncovering a novel paradigm in mTOR function.

PMID- 29337439
TI  - ?

PMID- 29337440
TI  - [Addictions].
AB  - This year, the actuality for addictions in this edition addresses four points.
      The disease model of addiction is criticized by the cognitive neurosciences which
      need to consider the agentivity of the persons. Regarding the societal actuality,
      clinical pharmacology review of cannabidiol presents an update on legal cannabis.
      The suicidality of excessive gamblers may be prevented specifically. Addiction
      and first psychotic episodes need an integrated care.

PMID- 29337438
TI  - 3D-e-Chem: Structural Cheminformatics Workflows for Computer-Aided Drug
      Discovery.
AB  - eScience technologies are needed to process the information available in many
      heterogeneous types of protein-ligand interaction data and to capture these data
      into models that enable the design of efficacious and safe medicines. Here we
      present scientific KNIME tools and workflows that enable the integration of
      chemical, pharmacological, and structural information for: i) structure-based
      bioactivity data mapping, ii) structure-based identification of scaffold
      replacement strategies for ligand design, iii) ligand-based target prediction,
      iv) protein sequence-based binding site identification and ligand repurposing,
      and v) structure-based pharmacophore comparison for ligand repurposing across
      protein families. The modular setup of the workflows and the use of well
      established standards allows the re-use of these protocols and facilitates the
      design of customized computer-aided drug discovery workflows.

PMID- 29337441
TI  - [Allergology and clinical immunology].
AB  - Hereditary angioedema (HA) is a disabling and potentially fatal condition. The
      management of HA includes treatment of acute attacks, short-term prophylaxis to
      prevent an attack, and long-term prophylaxis to minimize the frequency and
      severity of recurrent attacks. In this article, we will present new therapeutic
      alternatives for long term prophylaxis. Glucocorticoids (GC) usage leads to a
      number of severe side-effects. In giant cell arteritis, the use of tocilizumab in
      conjunction with low doses of GC reduces the number of relapses. In ANCA
      associated vasculitis the use of an anti-C5R (avacopan) alone or in conjunction
      with low doses of GC results in similar remission rates to those induced by high
      dose GC.

PMID- 29337442
TI  - [Angiology and haemostasis. Highlights on some new data in 2017].
AB  - New data support the fact that prophylactic anticoagulation with direct oral
      anticoagulants is effective and safe for the long-term prevention of venous
      thromboembolism. This type of treatment is dedicated for a subgroup of patients
      only, which is described in this article. With regard to major bleedings
      occurring with these anticoagulants, new data have been added to those already
      available for idarucizumab, a specific antagonist of dabigatran. Finally, we
      summarize the data regarding a breakthrough molecule, emicizumab, which could
      potentially open a new era in the management of people with haemophilia A.

PMID- 29337444
TI  - [Fumarates - far more than a dietary supplement].
AB  - Fumaric acid has an important role in the citric acid cycle. Its esters were
      first used by a German chemist to treat his own psoriasis, hypothesizing that the
      disease may be related to disturbances in this very cycle. Meanwhile, the
      mechanisms underlying its anti-inflammatory efficacy are much better understood.
      A monosubstance derived from the mix of esters used originally is now being
      authorized for treating multiple sclerosis, and in 2017 dimethylfumaric acid
      ester became a globally available option to treat psoriasis. This very practical
      therapeutic will most likely become quite popular amongst patients. Therefore,
      general practitioners might need to familiarize themselves with the profile of
      this drug, including its potential risks and some very rare but potentially
      important adverse effects.

PMID- 29337443
TI  - [Update in Surgical Oncology].
AB  - In 2017, data from large multicentre randomized controlled trials assessed the
      safety of minimally invasive techniques for liver or esophagus resection with
      similar oncologic outcome compared to open approach. Patients also benefit from
      progress in medical oncology in particular with the development of new targeted
      therapies, offering surgery to patients with initially non-resectable disease.
      The increase in complete tumor response after neoadjuvant treatment allows more
      conservative approaches, like organ preserving surgery for rectal cancer. The
      constant improvement in perioperative care and enhanced recovery programs
      (Enhanced Recovery After Surgery - ERAS) reduce both length of hospital stay and
      costs, decrease the risk of postoperative complications, and offer better quality
      of life to the patients.

PMID- 29337445
TI  - [News in diabetology 2017].
AB  - The field of diabetes is constantly evolving, with numerous new molecules
      reaching the market for the treatment of type 2 diabetes. Paradoxically, this
      drug jungle is difficult for the primary care physician and can lead to
      therapeutic inertia. The aim of this article is to discuss new molecules and new
      cardiovascular outcome studies that lead to changes in guidelines pertinent to
      the pharmacological treatment of type 2 diabetes.

PMID- 29337446
TI  - [Endocrinopathies induced by immune checkpoint inhibitors].
AB  - Immune checkpoint Inhibitors are new immunomodulatory treatments that have proven
      their anti-tumor efficacy in several advanced cancers. Nevertheless, their use
      has paved the way for multiple immunological adverse effects that affect many
      systems and organs including endocrine glands such as the pituitary, thyroid,
      adrenal and pancreas. Hypophysitis is the most common complication of anti-CTLA-4
      monoclonal antibodies, while anti-PD-1 and anti-PD-L1 antibodies cause more
      thyroid complications. Adrenal insufficiency and type 1 diabetes are relatively
      less common. Endocrinologists and primary care physicians as well as oncologists
      are likely to deal with these complications and as such, knowledge of these drugs
      and their side effects is essential for good practice.

PMID- 29337447
TI  - [Geriatric medicine].
AB  - 2017 highlights benefits of prevention. Better control of cardiovascular risk
      reduces the incidence of dementia and monthly high-dose vitamin D the incidence
      of respiratory infections in nursing home. Pre-operative geriatric assessment
      lowers by 20% the rate of delirium after hip-fracture surgery and complications
      in vascular surgery. Deleterious effects are also reported. High-dose vitamin D
      triples the rate of falls in supplemented residents and doesn't improve gait
      speed in sedentary men. Widely used in cardiovascular prevention, antithrombotic
      therapy is associated with an astonishing risk of subdural bleeding that further
      increases with the number of drugs combined together. Finally, the non
      pharmacological management of behavioral and psychotic symptoms in advanced
      dementia, although effective, doesn't reduce the associated burden for proxies.

PMID- 29337448
TI  - [Obstetrics].
AB  - During the past year, we have renewed interest in old well-known problems. New
      studies and guidelines have been issued about lung maturation in cases of preterm
      delivery after 37 weeks of gestation. Short term benefits have been proven but
      the number of cases needed to treat to prevent one case of respiratory
      complications is high and with possible neurological long-term effects. Also,
      several studies have shown the benefits of including the ultrasound measurement
      of the inferior segment of the uterus in order to attempt vaginal delivery after
      caesarean section with the lowest risk for uterine rupture, while others studies
      have shown the best procedure to close the uterus during cesarean section. And
      finally, we will discuss about an old friend: aspirin to reduce the risk of pre
      eclampsia.

PMID- 29337449
TI  - [Blood pressure management : what's new in 2017 ?]
AB  - In the last 2 years, the attention of hypertension specialists has been focused
      on the results of the SPRINT trial and its post-hoc analyses and its possible
      implications for the management of hypertensive patients. While waiting for new
      European hypertension guidelines due in 2018, the year 2017 can be considered as
      a year of transition. Yet, several interesting clinical studies have been
      published which may affect the future management of hypertension. Thus we shall
      discuss new data on the benefits of eating more fruits and vegetables on
      cardiovascular mortality, the " quadpill " concept, the impact of various non
      steroidal anti-inflammatory drugs on blood pressure and the most recent data on
      renal denervation.

PMID- 29337450
TI  - [Emergency medicine : update 2017].
AB  - Emergency medicine is part of the current stream of efficient and qualitative
      medicine : 1) the modified Valsava maneuver results in the resolution of almost
      50% of supra-ventricular tachycardia without any drug; 2) lung echography
      performed by emergency physicians is a very sensitive and specific diagnostic
      tool for most thoracic emergencies; 3) cardiopulmonary resuscitation initiated by
      lay-rescuers improves short and long-term outcome; 4) no anticoagulant treatment
      is warranted in distal deep vein thrombosis and 5) systematic unenhanced
      abdominal CT might improve evaluation of elderly patients with acute abdominal
      pain.

PMID- 29337451
TI  - [Nephrology].
AB  - New antidiabetic drugs which slow effectively the course of diabetic nephropathy
      are now available. There is no benefit of prophylactic hydratation to prevent
      contrast nephropathy in patients with moderate chronic kidney disease. In elderly
      hemodialysis patients, hemodiafiltration seems better tolerated than conventional
      hemodialysis, although there is a similar dialysis-induced myocardial stress with
      both methods. Role of de novo donor-specific antibodies is better characterized,
      which may subsequently lead to new treatments of graft rejection.

PMID- 29337452
TI  - [Neurology].
AB  - Ocrelizumab (Ocrevus), an anti-CD20 monoclonal antibody, has been approved for
      the treatment of multiple sclerosis. Eculizumab (Soliris) has been approved in
      several countries for refractory forms of generalized seropositive severe
      myasthenia gravis. A form of gene therapy, patisiran, has shown positive results
      in transthyretin familial amyloidosis. In the treatment of headaches,
      particularly migraines, non-pharmacological approaches have shown some
      interesting results. The criteria for Lewy body dementia have been revised.
      Generic use of lamotrigine does not result in recrudescence of epileptic seizures
      or adverse effects.

PMID- 29337453
TI  - [AMD and complement pathway in 2017].
AB  - AMD is the major cause of visual loss in individuals older than 50 in the western
      countries. Whilst tremendous progress has been made by the intraocular repeated
      injections of anti-VEGFs in wet AMD, no treatment is recognized to prevent
      progression of dry AMD, which represents more than 50 % of the cases.
      Interestingly, an over activation of the complement alternative pathway has been
      associated to both forms of AMD. But, several clinical studies have failed to
      demonstrate any efficacy of molecules blocking the complement pathway at various
      stage of its activation. In 2017, another failure was reported with lampalizumab
      after this drug succeeded in phase 2. Why such failure? What is the exact role of
      complement in AMD pathogenesis? Is complement regulation a hopeless pathway to
      follow in AMD? This article summarizes knowledge in the field.

PMID- 29337454
TI  - [Osteoporosis].
AB  - The risk for a second fracture within two years after a first one is high. Ten
      years denosumab treatment show favorable results with a risk of early vertebral
      fractures in patients with prevalent vertebral fractures when treatment is
      stopped. Teriparatide is more effective than risedronate to prevent vertebral and
      clinical fractures in high risk patients. Romosozumab acts as an anabolic agent
      in osteoporosis. Atypical femoral fractures associated with bisphosphonate
      treatment could be more frequent in patients with particular anatomical features.
      Management of osteoporosis treatment depends on the drug which is used and on the
      risk of fracture of the patient.

PMID- 29337455
TI  - [Pediatrics - New classification of seizures and epilepsies].
AB  - The International League Against Epilepsy published a new classification of
      epileptic seizures and epilepsies. It is more transparent and important notions
      like etiologies and comorbities have been added. The identification of seizures,
      epilepsies then epilepsy syndromes constitutes the three steps of this
      classification.

PMID- 29337456
TI  - [Pediatrics - Perthes disease : current knowledges and treatment].
AB  - Perthes's disease corresponds to an interruption of the vascularization of the
      epiphyseal nucleus of the femoral head followed by avascular necrosis. This
      necrosis weakens the bone and subchondral fractures associated with a deformation
      of the femoral head is seen. It is important not to miss an extrusion of the
      femoral head, which makes surgical treatment unavoidable. The loss of joint
      congruence causes functional limitations and represents an increased risk for
      early hip osteoarthritis. Non weight bearing limits the subchondral fractures,
      but requires an important adaptation from the patient and his entourage.

PMID- 29337457
TI  - [Pharmacovigilance update].
AB  - The main pharmacovigilance updates in 2017 are reviewed. Denosumab : rebound
      associated multiple vertebral fractures after discontinuation. Canagliflozine:
      increased risk of foot/leg amputations. Biologic and targeted cancer therapies,
      direct-acting antivirals for chronic hepatitis C: risk of hepatitis B
      reactivation. Checkpoint inhibitors : immune-related adverse events and graft
      rejection. Fingolimod : rebound-associated reactivation of MS following
      withdrawal. Daclizumab: risk of severe liver injury leading to restricted use in
      MS patients. Posaconazole: risk of overexposure when switching from oral
      suspension to tablets. Voriconazole: cutaneous squamous cell carcinoma under long
      term therapy. Proton pump inhibitors : early exposure might increase fracture
      risk in young children.

PMID- 29337458
TI  - [Pulmonary diseases. Asthma, COPD and sleep apnea syndrome].
AB  - Among the novelties described in the management of pulmonary disorders during the
      year 2017, we chose to describe three. First, the indication for inhaled
      glucocorticosteroids (ICS) in COPD has been revisited, because of their
      relationship with an increased occurence of pneumonia : ICS are now recommended
      only in severe COPD (GOLD D) with frequent exacerbations as second line
      treatment. Secondly, azithromycine has shown very promising results in poorly
      controlled severe asthma, with a significant impact on symptoms and
      exacerbations. Finally, despite the association between sleep apnea syndrome and
      cardiovascular morbidity, the prescription of CPAP in asymptomatic individuals as
      primary or secondary prevention is not supported by the recent literature.

PMID- 29337459
TI  - [Psychiatry].
AB  - Children of patients with psychiatric disorders are at higher risk to develop a
      psychiatric illness. In addition, phases of crisis and hospitalization of the
      parent are often traumatizing to the children, especially during childhood.
      Although a specific offer to face these issues is compulsory in some countries,
      such is not the case in Switzerland. In this paper we describe the implementation
      of a special offer for children of parents with mental illness (Famille +) in the
      service of general psychiatry at the Department of psychiatry of the Lausanne
      University hospital in Switzerland. We will also discuss the development and
      implementation of the Joint Crisis Plan, a collaborative tool where psychiatric
      patients and clinicians define the strategies that should be applied in case of
      crisis, which strengthens the empowerment of patients and their participation to
      decisions about their treatment.

PMID- 29337460
TI  - [Rheumatology. Checkpoint-induced autoimmunity - birth of a new disease].
AB  - Tumor cells express checkpoint proteins in order to prevent an immune reaction by
      T-cells. Checkpoint inhibitors are successfully used in oncology to unleash a
      cytotoxic immune response. Unfortunately this treatment increasingly leads to
      immune-related adverse events which resemble various primary autoimmune disorders
      known in rheumatology. Potentially, checkpoint dysfunction also underlies
      rheumatic diseases which would open the way for new treatment options to restore
      immune tolerance.

PMID- 29337461
TI  - [Urology].
AB  - This article points at recent developments in urology in the field of malignant
      diseases of the urinary system and the diagnostic and therapeutic management of
      benign conditions as well, that occur frequently in our ageing population.

PMID- 29337462
TI  - [Antiretroviral treatments : towards simplified regimens ?]
AB  - The chronicity of HIV infection and the use of antiretroviral therapy among all
      individuals living with HIV necessitate new treatment strategies. Alternatives to
      lifelong tri-therapy treatment are under investigation with the aim to improve
      the quality of life of patients. New therapies with longer half-lives or "
      biological " treatments are also under study in clinical trials in order to
      develop streamlined maintenance strategies. These simplified therapies represent
      the near future of HIV management both with regards to less toxic molecules and a
      change in the traditional dogma of tri-therapy, including the daily dose thanks
      to the possibility of dosage only on certain weekdays or via molecules under
      development with a long duration of action.

PMID- 29337463
TI  - [Virtual reality: a tool that can be used in outpatient diabetes services].
AB  - Health-related emerging technologies are growing fast. The use of virtual reality
      in diabetes outpatient care still remains unprecedented, notably in Switzerland.
      Thus, the Programme cantonal Diabete led a pilot study to assess the feasibility
      of an immersive application in such an outpatient setting. Results emphasize that
      this device is practicable and useful in diabetes care. Patients and their
      relatives overall appreciate the game, each of them for specific reasons: playful
      quality, opportunity to " learn differently " or to exchange about the subjective
      experience. Furthermore, there is no restraint (age, language, educational
      level...) in the ability to use such a device, except for emerging technologies
      habit.

PMID- 29337464
TI  - ?

PMID- 29337465
TI  - ?

PMID- 29337466
TI  - ?

PMID- 29337467
TI  - ?

PMID- 29337468
TI  - ?

PMID- 29337469
TI  - ?

PMID- 29337470
TI  - Multifunctional pH-Responsive Folate Receptor Mediated Polymer Nanoparticles for
      Drug Delivery.
AB  - Multifunctional pH-responsive folate receptor mediated targeted polymer
      nanoparticles (TPNps) were developed for docetaxel (DTX) delivery based on
      poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene
      glycol)poly (beta-amino ester) (P123-PAE) and poly(ethylene glycol)-block
      poly(propylene glycol)-block-poly(ethylene glycol)-folate (P123-FA) copolymers.
      The DTX was loaded into the TPNps with a decent drug loading content of 15.02 +/-
      0.14 wt%. In vitro drug release results showed that the DTX was released from the
      TPNps at a pH-dependent manner. Tetrazolium dye (MTT) assay revealed that the
      bland polymer nanoparticles displayed almost nontoxicity at 200 MUg/mL
      concentration. However, the DTX-loaded TPNps showed high anti-tumor activity at
      low IC50 (0.72 MUg/mL) for MCF-7 cells following 48 h incubation. Cellular uptake
      experiments revealed that the TPNps had higher degree of cellular uptake than
      nontargeted polymer nanoparticles, indicating that the nanoparticles were
      internalized into the cells via FA receptor-mediated endocytosis. Moreover, the
      cellular uptake pathways for the FA grafted polymer were involved in energy
      dependent, clathrin-mediated and caveolae-mediated endocytosis. The cell killing
      effect and cellular uptake of the DTX-TPNps by the MCF-7 cells were all enhanced
      by about two folds at pH 5.5 when compared with pH 7.4. The TPNps also
      significantly prolonged the in vivo retention time for the DTX. These results
      suggest that the biocompatible pH responsive folate-modified polymer
      nanoparticles present a promising safe nanosystem for intracellular targeted
      delivery of DTX.

PMID- 29337484
TI  - Simultaneous Targeting of Differentiated Breast Cancer Cells and Breast Cancer
      Stem Cells by Combination of Docetaxel- and Sulforaphane-Loaded Self-Assembled
      Poly(D, L-lactide-co-glycolide)/Hyaluronic Acid Block Copolymer-Based
      Nanoparticles.
AB  - Breast cancer stem cells (BCSCs) are implicated in the initiation and progression
      of breast cancer and are responsible for metastasis and recurrence. In this
      study, we attempted to simultaneously target differentiated breast cancer cells
      (DBCCs) and BCSCs by using a combination of docetaxel (DTX)- and sulforaphane
      (SFN)-loaded poly(D, L-lactide-coglycolide)/hyaluronic acid (PLGA-b-HA)-based
      nanoparticles. BCSCs were identified as having an ESA+CD44+CD24- phenotype, which
      exhibited docetaxel resistance. Drug-loaded nanoparticles exhibited enhanced
      cytotoxicity towards both DBCCs and BCSCs compared with free drugs. SFN-loaded
      nanoparticles were more effective in inhibiting BCSCs than free SFN in vitro by
      down-regulating beta-catenin expression. In vivo analysis of anti-tumor activity
      showed that the combination therapy with DTX- and SFN-loaded nanoparticles had
      the strongest antitumor efficacy. In vivo analysis of anti-BCSCs activity showed
      that the self-renewal ability of BCSCs was strongly inhibited in DTX- and SFN
      loaded nanoparticle-treated groups. In conclusion, the combination of SFN- and
      DTX-loaded PLGA-b-HA nanoparticles shows therapeutic potential in the treatment
      of breast cancer by simultaneously targeting DBCCs and BCSCs.

PMID- 29337485
TI  - A Novel Thermochromic Liquid Crystal Fabric Design for the Early Detection of
      High-Risk Foot Complications
AB  - Background: We developed a prototype of a novel thermochromic liquid crystal
      (TLC)-coated fabric with an extended temperature range and enhanced sensitivity.
      By incorporating color and pattern recognition into the fabric, rapid
      determination of the underlying pedal temperature is facilitated. The purpose of
      this study was to evaluate the accuracy of the TLC fabric as a potential
      diagnostic aid for identifying complications in the high-risk foot. Methods: The
      hands of 100 individuals were used to compare the mean maximum temperatures
      indicated by the fabric versus standard thermal camera images. Findings were
      statistically analyzed using a paired <italic>t</italic> test, with significance
      defined as <italic>P</italic> < .05. Results: Except for the tip of the thumb and
      regions in the palm, there were no statistically significant differences between
      mean maximum temperatures measured with the thermal camera and those detected
      with the TLC fabric. Minor differences were relatively consistent in all nine
      regions of the hand and were not considered to be clinically significant.
      Conclusions: Using direct visual analysis, we demonstrated that a novel TLC
      fabric could accurately map temperatures in the palmar surface of the hand. The
      findings support the continued development of a temperature-sensitive sock that
      can be used in the home to monitor for temperature changes that may indicate the
      onset of complications in the high-risk foot.

PMID- 29337486
TI  - Improving risk stratification among veterans diagnosed with prostate cancer:
      impact of the 17-gene prostate score assay.
AB  - BACKGROUND: Active surveillance (AS) has been widely implemented within Veterans
      Affairs' medical centers (VAMCs) as a standard of care for low-risk prostate
      cancer (PCa). Patient characteristics such as age, race, and Agent Orange (AO)
      exposure may influence advisability of AS in veterans. The 17-gene assay may
      improve risk stratification and management selection. OBJECTIVES: To compare
      management strategies for PCa at 6 VAMCs before and after introduction of the
      Oncotype DX Genomic Prostate Score (GPS) assay. STUDY DESIGN: We reviewed records
      of patients diagnosed with PCa between 2013 and 2014 to identify management
      patterns in an untested cohort. From 2015 to 2016, these patients received GPS
      testing in a prospective study. Charts from 6 months post biopsy were reviewed
      for both cohorts to compare management received in the untested and tested
      cohorts. SUBJECTS: Men who just received their diagnosis and have National
      Comprehensive Cancer Network (NCCN) very low-, low-, and select cases of
      intermediate-risk PCa. RESULTS: Patient characteristics were generally similar in
      the untested and tested cohorts. AS utilization was 12% higher in the tested
      cohort compared with the untested cohort. In men younger than 60 years,
      utilization of AS in tested men was 33% higher than in untested men. AS in tested
      men was higher across all NCCN risk groups and races, particular in low-risk men
      (72% vs 90% for untested vs tested, respectively). Tested veterans exposed to AO
      received less AS than untested veterans. Tested nonexposed veterans received 19%
      more AS than untested veterans. Median GPS results did not significantly differ
      as a factor of race or AO exposure. CONCLUSIONS: Men who receive GPS testing are
      more likely to utilize AS within the year post diagnosis, regardless of age,
      race, and NCCN risk group. Median GPS was similar across racial groups and AO
      exposure groups, suggesting similar biology across these groups. The GPS assay
      may be a useful tool to refine risk assessment of PCa and increase rates of AS
      among clinically and biologically low-risk patients, which is in line with
      guideline-based care.

PMID- 29337487
TI  - Production of Nanoscale Vibration for Stimulation of Human Mesenchymal Stem
      Cells.
AB  - Mechanical stimulation is becoming a common technique for manipulating cell
      behaviour in bioengineering with applications in tissue engineering and possibly
      regenerative therapy. Living organisms show biological responses in vivo and in
      vitro to various types of mechanical stimulation including vibration. The
      development of apparatus to produce vertical motions of nanoscale amplitude is
      detailed and their effect on mouse endothelial (Le2) and human mesenchymal stem
      cells (hMSCs) is investigated. Piezo ceramic actuators and aluminium
      reinforcement were utilised along with laser interferometry to ensure amplitude
      consistency at the nanometre level across a cell culture substrate. Peak force
      applied to the cells was estimated to be of nN magnitude at frequencies of 500
      and 1000 Hz. Morphological changes in the cytoskeleton were found for both cell
      types along with increased MSC proliferation after 1 week of stimulation at 500
      Hz. Changes in the nuclear size of MSCs after stimulation were also found.

PMID- 29337488
TI  - Optimization of Transforming Growth Factor-beta1 siRNA Loaded Chitosan
      Tripolyphosphate Nanoparticles for the Treatment of Colorectal Cancer Hepatic
      Metastasis in a Mouse Model.
AB  - Metastatic liver disease is the most frequent complication of colorectal cancer
      (CRC), and the development of liver-targeted nanoparticles for drug delivery is a
      promising therapeutic approach. However, to improve the efficacy of passive drug
      delivery, its release rate at the sites of liver metastases should be maximized
      while minimizing drug uptake in nontargeted cells. Herein, we report the
      development and use of tripolyphosphate (TPP) modified chitosan (CS)
      nanoparticles loaded with small interfering RNA (siRNA) directed against
      transforming growth factor beta1 (TGF-beta1), which promotes tumorigenesis in
      advanced CRC. The nanoparticles efficiently inhibited CRC hepatic metastasis in
      an animal model. Particles of 300 nm in size and zeta potential at 20 mV showed a
      more striking liver-targeting effect. A weight ratio of CS/TPP of 8:1 for
      particles with TGF- beta1 siRNA loaded at a concentration of 20 MUM at pH 7.5
      showed good pH-responsive drug release when exposed to a CRC homogenate at pH
      6.5. In vivo, CS-TPP/TGF- beta1 siRNA nanoparticles significantly reduced the
      volume and number of CRC metastatic foci. This was accompanied by the
      downregulation of TGF- beta1 expression in the tumor microenvironment, inhibition
      of tumor associated macrophage formation, and improvement of the immune
      microenvironment. These results indicate that it is possible to achieve effective
      passive liver targeting by optimizing the processing parameters. The design of
      nanoparticles carrying siRNA against overexpressed oncogenes provides an
      excellent platform for the development of an efficient liver cancer therapy.

PMID- 29337489
TI  - An Investigation of the Usability of Solid Lipid Nanoparticles Radiolabelled with
      Tc-99m as Imaging Agents in Liver-Spleen Scintigraphy.
AB  - In this work, solid lipid nanoparticles (SLNs) were prepared by microemulsion and
      ultrasonication methods in the first stage of the production process of 99mTc
      SLNs, which is considered to be an alternative radiopharmaceutical for the liver
      spleen scintigraphy within the nuclear medicine. The laser diffraction (LD) and X
      ray diffraction (XRD) analysis showed that these particles were at nano scale and
      had beta' polymorph structure, respectively. It was observed that there was no
      interaction between the solid lipid and the surfactant molecules by fourier
      transform infrared spectroscopy (FT-IR). The scanning electron microscope (SEM)
      and transmission electron microscopy (TEM) images were taken and seen that the
      SLNs were spherical and at nano scale. Thermogravimetric analysis (TGA) for
      stability confirmed that they were stable for temperature variations. In the
      second stage of the study, the SLNs were successfully labeled with 99mTc. The
      radiolabeling efficiency was found to be greater than %95 and in vivo studies
      were performed on experimental rabbits using scintigraphic methods. When the
      obtained images were examined, the uptake was observed in the heart, the lungs,
      the liver, and the spleen. It was concluded that SLNs labeled with 99mTc could be
      a selective imaging agent. It was asserted to be a new radiopharmaceutical,
      especially as an alternative to the 99mTc-labeled compounds used in the liver and
      spleen imaging in colloid scintigraphy.

PMID- 29337490
TI  - PEG-Poly(amino acid)s/MicroRNA Complex Nanoparticles Effectively Arrest the
      Growth and Metastasis of Colorectal Cancer.
AB  - One of the biggest challenges in developing microRNA (miRNA) based therapeutics
      is the method of delivery. Herein we report the design and synthesis of mPEG
      poly(amino acid)s, which we used as a novel nanocarrier for the delivery of miRNA
      139-5p. The PEG-poly(amino acid)s/miRNA-139-5p nanoparticle complex is more
      effective at suppressing tumor growth and migration in mice with colorectal
      cancer than when treated with miRNA-139-5p solution and blank nanoparticles
      individually. Our results suggest that PEG-poly(amino acid)s are a promising non
      viral gene vector for the delivery of miRNAs to treat cancers.

PMID- 29337491
TI  - Gold Nanocrystals with Well-Defined Crystallographic {111} Facets Suppress
      Pathological Neovascularization.
AB  - Vascular endothelial growth factor (VEGF) is a main factor in pathological
      neovascularization in various human diseases including age-related macular
      degeneration, cancer, and diabetic complications. Interestingly, gold nanospheres
      are known to bind to VEGF and to suppress VEGF-mediated angiogenesis. The anti
      angiogenic effects are known to be governed by the size and surface charge of the
      nanoparticles. However, studies on the role of the shape in biological actions
      are limited. In this study, we investigate the anti-angiogenic properties of
      nanocrystals that have well-defined crystallographic {111} facets. Single
      crystalline icosahedral and octahedral gold nanocrystals effectively scavenge
      VEGF just as nanospheres with similar diameter. In addition, they suppress the in
      vitro VEGF-induced activation of the VEGF receptor and the proliferation of
      endothelial cells. They also significantly inhibit in vivo VEGF-mediated retinal
      vascular permeability. These results thus suggest that gold nanocrystals with
      {111} facets can provide a useful platform for nanoparticle-based treatment of
      VEGF-driven pathological neovascularization beyond their current optical and
      catalytic applications.

PMID- 29337492
TI  - Nanoparticle-Based Mucosal Vaccines Targeting Tumor-Associated Antigens to Human
      Dendritic Cells.
AB  - The induction of effective T cell-mediated immune responses is the main objective
      of vaccination against cancer. T cell responses are initiated by dendritic cells
      (DCs) as the most potent antigen-presenting cells. Designing vaccines for
      efficient delivery of tumor antigens to these cells in immunogenic fashion is,
      therefore, a major task in tumor immunology. In this human-based in vitro study
      we investigated the suitability of different polymeric nanoparticles (NPs) for
      delivering the tumor-associated antigen Her2/neu to DCs for induction of T cell
      responses by mucosal vaccination. The natural polymer chitosan and novel
      functionalized PLGA-based polymers were used for NP production. All NPs were
      efficiently taken up by DCs. Her2/neu delivered by NPs was more efficiently
      processed and presented by DCs than the soluble protein and induced more vigorous
      CD4+ and CD8+ T cell proliferation, and cytotoxic T cells. Testing the
      suitability of this platform for mucosal vaccination, NPs were applied to the
      apical side of an intestinal epithelium model and found to be efficiently
      transported across the epithelial layer to become available to basolateral DCs.
      Thus, chitosan and PLGA-based NPs are efficient carriers for delivery of antigens
      to DCs for induction of T cell-based immunity, and suitable for mucosal vaccine
      formulations.

PMID- 29337493
TI  - Cellular Internalization Mechanisms of Polyanhydride Particles: Implications for
      Rational Design of Drug Delivery Vehicles.
AB  - Polyanhydride nanoparticles have emerged as a versatile delivery platform, due to
      their ability to encapsulate diverse drugs, immunogens, antibodies, and proteins.
      However, mechanistic studies on the effects of particle chemistry interactions
      with immune cells have yet to be described. Understanding the mechanism by which
      these particles are internalized by immune cells will enable rational selection
      of delivery vehicles for specific applications. In the present study, the
      internalization, mechanism(s) of uptake by monocytes, and intracellular fate of
      polyanhydride nanoparticles were evaluated using copolymers based on 1,6-bis(p
      carboxyphenoxy)hexane (CPH), sebacic acid (SA), and 1,8-bis(p-carboxyphenoxy)3,6
      dioxaoctane (CPTEG). The results showed that 20:80 CPH:SA and 20:80 CPTEG:CPH
      nanoparticles were internalized to a greater extent by monocytes as compared to
      the 50:50 CPH:SA and 50:50 CPTEH:CPH nanoparticles. Further, cytochalasin-D
      treatment of cells inhibited uptake of all the particles, regardless of
      chemistry, indicating that actinmediated uptake is the primary mechanism of
      cellular entry for these particles. The insights gained from these studies were
      used to identify lead nanoparticle formulations to enhance treatment of
      intracellular bacterial infections. The use of doxycycline-loaded nanoparticles
      exhibited enhanced therapeutic efficacy compared to soluble drug in treating
      monocyte monolayers infected with the virulent intracellular pathogen Brucella
      abortus. Altogether, these studies demonstrate how rational design and selection
      of nanoscale delivery platforms can be used for a wide spectrum of biomedical
      applications.

PMID- 29337526
TI  - Carbon Nanotube Web with Carboxylated Polythiophene "Assist" for High-Performance
      Battery Electrodes.
AB  - A carbon nanotube (CNT) web electrode comprising magnetite spheres and few-walled
      carbon nanotubes (FWNTs) linked by the carboxylated conjugated polymer, poly[3
      (potassium-4-butanoate) thiophene] (PPBT), was designed to demonstrate benefits
      derived from the rational consideration of electron/ion transport coupled with
      the surface chemistry of the electrode materials components. To maximize
      transport properties, the approach introduces monodispersed spherical Fe3O4
      (sFe3O4) for uniform Li+ diffusion and a FWNT web electrode frame that affords
      characteristics of long-ranged electronic pathways and porous networks. The
      sFe3O4 particles were used as a model high-capacity energy active material, owing
      to their well-defined chemistry with surface hydroxyl (-OH) functionalities that
      provide for facile detection of molecular interactions. PPBT, having a pi
      conjugated backbone and alkyl side chains substituted with carboxylate moieties,
      interacted with the FWNT pi-electron-rich and hydroxylated sFe3O4 surfaces, which
      enabled the formation of effective electrical bridges between the respective
      components, contributing to efficient electron transport and electrode stability.
      To further induce interactions between PPBT and the metal hydroxide surface,
      polyethylene glycol was coated onto the sFe3O4 particles, allowing for facile
      materials dispersion and connectivity. Additionally, the introduction of carbon
      particles into the web electrode minimized sFe3O4 aggregation and afforded more
      porous FWNT networks. As a consequence, the design of composite electrodes with
      rigorous consideration of specific molecular interactions induced by the surface
      chemistries favorably influenced electrochemical kinetics and electrode
      resistance, which afforded high-performance electrodes for battery applications.

PMID- 29337527
TI  - Firefly-like Water Splitting Cells Based on FRET Phenomena with Ultrahigh
      Performance over 12.
AB  - A firefly-like chemiluminescence reaction was utilized in a ZrO2 nanoparticle
      matrix of water splitting cells, where the chlorophyll of Lantana camara was used
      as the major photosensitizer to excite electrons to the conduction band of ZrO2.
      The fluorescence resonance energy transfer (FRET) was induced by rubrene, a
      firefly-like chemiluminescence molecule, and Lantana camara chlorophyll combined
      with 9,10-diphenylanthracene. The ZrO2 nanoparticle film coated by the
      chlorophyll of Lantana camara and 9,10-diphenylanthracene under chemiluminescence
      irradiation in 1 M KHCO3 water solution demonstrated the highest photocurrent
      density (88.1 A/m2) and the highest water splitting efficiency (12.77%).

PMID- 29337528
TI  - Directed Self-Assembly of Dipeptide Single Crystal in a Capillary.
AB  - Controlled growth of one-dimensional nanostructures is playing a key role in
      creating types of materials for functional devices. Here, we report procedures
      for controlled assembly of the dipeptide diphenylalanine (FF) into aligned and
      ultralong single crystals in a capillary. With the evaporation of solvent,
      nucleation of the crystal occurred in the confined region, and the crystal grew
      continuously with a supply of molecules from the concentration gradient system
      inside the capillary. Based on the "Knudsen regime", an ultralong aligned
      individual FF single crystal possessing an active optical waveguide property at
      macroscopic length scale could be obtained. Moreover, capillary is also an
      effective microdevice to investigate the disassembly process of the FF single
      crystals. This strategy has potentials to broaden the range of applications of
      aligned organic nanomaterials.

PMID- 29337530
TI  - Label-Free and Ultrasensitive Biomolecule Detection Based on Aggregation Induced
      Emission Fluorogen via Target-Triggered Hemin/G-Quadruplex-Catalyzed Oxidation
      Reaction.
AB  - Fluorescence biosensing strategy has drawn substantial attention due to their
      advantages of simplicity, convenience, sensitivity, and selectivity, but
      unsatisfactory structure stability, low fluorescence quantum yield, high cost of
      labeling, and strict reaction conditions associated with current fluorescence
      methods severely prohibit their potential application. To address these
      challenges, we herein propose an ultrasensitive label-free fluorescence biosensor
      by integrating hemin/G-quadruplex-catalyzed oxidation reaction with aggregation
      induced emission (AIE) fluorogen-based system. l-Cysteine/TPE-M, which is
      carefully and elaborately designed and developed, obviously contributes to strong
      fluorescence emission. In the presence of G-rich DNA along with K+ and hemin,
      efficient destruction of l-cysteine occurs due to hemin/G-quadruplex-catalyzed
      oxidation reactions. As a result, highly sensitive fluorescence detection of G
      rich DNA is readily realized, with a detection limit down to 33 pM. As a
      validation for the further development of the proposed strategy, we also
      successfully construct ultrasensitive platforms for microRNA by incorporating the
      l-cysteine/TPE-M system with target-triggered cyclic amplification reaction.
      Thus, this proposed strategy is anticipated to find use in basic biochemical
      research and clinical diagnosis.

PMID- 29337529
TI  - Glutathione-Capped Ag2S Nanoclusters Inhibit Coronavirus Proliferation through
      Blockage of Viral RNA Synthesis and Budding.
AB  - Development of novel antiviral reagents is of great importance for the control of
      virus spread. Here, Ag2S nanoclusters (NCs) were proved for the first time to
      possess highly efficient antiviral activity by using porcine epidemic diarrhea
      virus (PEDV) as a model of coronavirus. Analyses of virus titers showed that Ag2S
      NCs significantly suppressed the infection of PEDV by about 3 orders of magnitude
      at the noncytotoxic concentration at 12 h postinfection, which was further
      confirmed by the expression of viral proteins. Mechanism investigations indicated
      that Ag2S NCs treatment inhibits the synthesis of viral negative-strand RNA and
      viral budding. Ag2S NCs treatment was also found to positively regulate the
      generation of IFN-stimulating genes (ISGs) and the expression of proinflammation
      cytokines, which might prevent PEDV infection. This study suggest the novel
      underlying of Ag2S NCs as a promising therapeutic drug for coronavirus.

PMID- 29337531
TI  - Branched Glycerol-Based Copolymer with Ultrahigh p65 siRNA Delivery Efficiency
      for Enhanced Cancer Therapy.
AB  - The small interfering RNA (siRNA) is emerging as a potential therapeutic for the
      treatment of various diseases because of the targeted gene silencing capability.
      The suppression of p65 expression has shown great potential in various cancer
      treatments. However, various substantial obstacles limit its clinical
      applications, including low cellular uptake, instability, and cytotoxicity of
      delivery vehicles. We show a highly branched and biocompatible glycerol-based
      copolymer (HBGC) to effectively deliver siRNA for excellent p65 gene silencing
      and safe lung cancer treatment in vitro and in vivo. HBGCs could be synthesized
      through a facile and modular one-spot Michael addition. HBGCs effectively protect
      siRNA in serum, enhance cellular uptake of siRNA, and show negligible
      cytotoxicity in various cells (A549, HeLa, HepG2, and C2C12). Additionally, the
      HBGC-siRNA complex potently downregulates the p65 expression in A549 cancer cells
      (almost the highest value of 96% in reported references) and enhances the
      cellular apoptosis compared to that of commercial transfection agents
      polyethyleneimine 25 kDa and Lipofectamine 2000. The HBGC-siRNA complex
      demonstrated significantly increased accumulation in the tumor sites and enhanced
      downregulation of p65 gene and cancer cell apoptosis. Furthermore, the tumor
      growth could be significantly inhibited in a subcutaneous lung tumor model with
      negligible adverse effects.

PMID- 29337532
TI  - Biotemplated Morpho Butterfly Wings for Tunable Structurally Colored
      Photocatalysts.
AB  - Morpho sulkowskyi butterfly wings contain naturally occurring hierarchical
      nanostructures that produce structural coloration. The high aspect ratio and
      surface area of these wings make them attractive nanostructured templates for
      applications in solar energy and photocatalysis. However, biomimetic approaches
      to replicate their complex structural features and integrate functional materials
      into their three-dimensional framework are highly limited in precision and
      scalability. Herein, a biotemplating approach is presented that precisely
      replicates Morpho nanostructures by depositing nanocrystalline ZnO coatings onto
      wings via low-temperature atomic layer deposition (ALD). This study demonstrates
      the ability to precisely tune the natural structural coloration while also
      integrating multifunctionality by imparting photocatalytic activity onto fully
      intact Morpho wings. Optical spectroscopy and finite-difference time-domain
      numerical modeling demonstrate that ALD ZnO coatings can rationally tune the
      structural coloration across the visible spectrum. These structurally colored
      photocatalysts exhibit an optimal coating thickness to maximize photocatalytic
      activity, which is attributed to trade-offs between light absorption and
      catalytic quantum yield with increasing coating thickness. These multifunctional
      photocatalysts present a new approach to integrating solar energy harvesting into
      visually attractive surfaces that can be integrated into building facades or
      other macroscopic structures to impart aesthetic appeal.

PMID- 29337533
TI  - Localized Fe(II)-Induced Cytotoxic Reactive Oxygen Species Generating Nanosystem
      for Enhanced Anticancer Therapy.
AB  - The anticancer therapy on the basis of reactive oxygen species (ROS)-mediated
      cellular apoptosis has achieved great progress. However, this kind of theraputic
      strategy still faces some challenges such as light, photosensitizer and oxygen
      (O2) dependence. In this article, a ROS-mediated anticancer therapy independent
      of light, photosensitizer and oxygen was established based on a Fe2+-induced ROS
      generating nanosystem. First, artemisinin (ART) was loaded in porous magnetic
      supraparticles (MSP) by a nanodeposition method. Then, the poly(aspartic acid)
      based polymer, which consisted of dopamine, indocyanine green, and polyethylene
      glycol side chain, was coated onto the surface of ART-loaded MSP. When the
      nanoparticles entered into cancer cells, a reaction of Fe2+-mediated cleavage of
      the endoperoxide bridge contained in ART occurred and subsequent a large amount
      of ROS was generated. Moreover, a NIR light was used to effectively increase the
      local temperature of tumor in virtue of the superior photothermal effects of MSP,
      which enabled us to accelerate the ROS generation and achieved an enhanced ROS
      yield. The newly developed nanodrug system displayed a high level of
      intracellular ROS generation, leading to the desired killing efficacy against
      malignant cells and solid tumor. This smart nanosystem holds great potential to
      overcome the existing barrier in PDT and opens a promising avenue for anticancer
      therapy.

PMID- 29337534
TI  - Highly Luminescent Encapsulated Narrow Bandgap Polymers Based on
      Diketopyrrolopyrrole.
AB  - We present the synthesis and characterization of a series of encapsulated
      diketopyrrolopyrrole red-emitting conjugated polymers. The novel materials
      display extremely high fluorescence quantum yields in both solution (>70%) and
      thin film (>20%). Both the absorption and emission spectra show clearer, more
      defined features compared to their naked counterparts demonstrating the
      suppression of inter and intramolecular aggregation. We find that the
      encapsulation results in decreased energetic disorder and a dramatic increase in
      backbone colinearity as evidenced by scanning tunnelling microscopy. This study
      paves the way for diketopyrrolopyrrole to be used in emissive solid state
      applications and demonstrates a novel method to reduce structural disorder in
      conjugated polymers.

PMID- 29337535
TI  - Anion-Mediated Photophysical Behavior in a C60 Fullerene [3]Rotaxane Shuttle.
AB  - By addressing the challenge of controlling molecular motion, mechanically
      interlocked molecular machines are primed for a variety of applications in the
      field of nanotechnology. Specifically, the designed manipulation of communication
      pathways between electron donor and acceptor moieties that are strategically
      integrated into dynamic photoactive rotaxanes and catenanes may lead to efficient
      artificial photosynthetic devices. In this pursuit, a novel [3]rotaxane molecular
      shuttle consisting of a four-station bis-naphthalene diimide (NDI) and central
      C60 fullerene bis-triazolium axle component and two mechanically bonded
      ferrocenyl-functionalized isophthalamide anion binding site-containing
      macrocycles is constructed using an anion template synthetic methodology. Dynamic
      coconformational anion recognition-mediated shuttling, which alters the relative
      positions of the electron donor and acceptor motifs of the [3]rotaxane's
      macrocycle and axle components, is demonstrated initially by 1H NMR spectroscopy.
      Detailed steady-state and time-resolved UV-vis-IR absorption and emission
      spectroscopies as well as electrochemical studies are employed to further probe
      the anion-dependent positional macrocycle-axle station state of the molecular
      shuttle, revealing a striking on/off switchable emission response induced by
      anion binding. Specifically, the [3]rotaxane chloride coconformation, where the
      ferrocenyl-functionalized macrocycles reside at the center of the axle component,
      precludes electron transfer to NDI, resulting in the switching-on of emission
      from the NDI fluorophore and concomitant formation of a C60 fullerene-based
      charge-separated state. By stark contrast, in the absence of chloride as the
      hexafluorophosphate salt, the ferrocenyl-functionalized macrocycles shuttle to
      the peripheral NDI axle stations, quenching the NDI emission via formation of a
      NDI-containing charge-separated state. Such anion-mediated control of the
      photophysical behavior of a rotaxane through molecular motion is unprecedented.

PMID- 29337536
TI  - Correction to "Adaptation in Constitutional Dynamic Libraries and Networks,
      Switching between Orthogonal Metalloselection and Photoselection Processes".

PMID- 29337537
TI  - Microplastic Effect Thresholds for Freshwater Benthic Macroinvertebrates.
AB  - Now that microplastics have been detected in lakes, rivers, and estuaries all
      over the globe, evaluating their effects on biota has become an urgent research
      priority. This is the first study that aims at determining the effect thresholds
      for a battery of six freshwater benthic macroinvertebrates with different species
      traits, using a wide range of microplastic concentrations. Standardized 28 days
      single species bioassays were performed under environmentally relevant exposure
      conditions using polystyrene microplastics (20-500 MUm) mixed with sediment at
      concentrations ranging from 0 to 40% sediment dry weight (dw). Microplastics
      caused no effects on the survival of Gammarus pulex, Hyalella azteca, Asellus
      aquaticus, Sphaerium corneum, and Tubifex spp. and no effects were found on the
      reproduction of Lumbriculus variegatus. No significant differences in growth were
      found for H. azteca, A. aquaticus, S. corneum, L. variegatus, and Tubifex spp.
      However, G. pulex showed a significant reduction in growth (EC10 = 1.07% sediment
      dw) and microplastic uptake was proportional with microplastic concentrations in
      sediment. These results indicate that although the risks of environmentally
      realistic concentrations of microplastics may be low, they still may affect the
      biodiversity and the functioning of aquatic communities which after all also
      depend on the sensitive species.

PMID- 29337538
TI  - Sustainable Polyester Elastomers from Lactones: Synthesis, Properties, and
      Enzymatic Hydrolyzability.
AB  - Chemically cross-linked elastomers are an important class of polymeric materials
      with excellent temperature and solvent resistance. However, nearly all elastomers
      are petroleum-derived and persist in the environment or in landfills long after
      they are discarded; this work strives to address these issues by demonstrating
      the synthesis of renewable, enzymatically hydrolyzable, and mechanically
      competitive polyester elastomers. The elastomers described were synthesized using
      a novel bis(beta-lactone) cross-linker and star-shaped, hydroxyl-terminated
      poly(gamma-methyl-epsilon-caprolactone). Using model compounds, we determined
      that the bis(beta-lactone) cross-linker undergoes acyl bond cleavage to afford
      beta-hydroxyesters at the junctions. The mechanical properties of the cross
      linked materials were tunable and competitive with a commodity rubber band.
      Furthermore, the elastomers demonstrated high thermal stability and a low glass
      transition (-50  degrees C), indicating a wide range of use temperatures. The
      polyester networks were also subjected to enzymatic hydrolysis experiments to
      investigate the potential for these materials to biodegrade in natural
      environments. We found that they readily hydrolyzed at neutral pH and
      environmentally relevant temperatures (2-40  degrees C); complete hydrolysis was
      achieved in all cases at temperature-dependent rates. The results presented in
      this work exemplify the development of high performance yet sustainable
      alternatives to conventional elastomers.

PMID- 29337539
TI  - A Comparative IRMPD and DFT Study of Fe3+ and UO22+ Complexation with N
      Methylacetohydroxamic Acid.
AB  - Iron(III) and uranyl complexes of N-methylacetohydroxamic acid (NMAH) have been
      investigated by mass spectrometry, infrared multiphoton dissociation (IRMPD)
      spectroscopy, and density functional theory (DFT) calculations. A comparison
      between IRMPD and theoretical IR spectra enabled one to probe the structures for
      some selected complexes detected in the gas phase. The results show that
      coordination of Fe3+ and UO22+ by hydroxamic acid is of a very similar nature.
      Natural bond orbital analysis suggests that bonding in uranyl complexes possesses
      a slightly stronger ionic character than that in iron complexes. Collision
      induced dissociation (CID), IRMPD, and 18O-labeling experiments unambiguously
      revealed a rare example of the U?O bond activation concomitant with the
      elimination of a water molecule from the gaseous [UO2(NMA)(NMAH)2]+ complex. The
      U?O bond activation is observed only for complexes with one monodentate NMAH
      molecule forming a hydrogen bond toward one "yl" oxygen atom, as was found by DFT
      calculations. This reactivity might explain oxygen exchange observed for uranyl
      complexes.

PMID- 29337540
TI  - Enhanced Degradation of Pesticide Dichlorophen by Laccase Immobilized on
      Nanoporous Materials: A Cytotoxic and Molecular Simulation Investigation.
AB  - Use of pesticides is usually related to overproduction of crops in order to
      overcome worldwide demand of food and alimentary safety. Nevertheless, pesticides
      are environmental persistent molecules, such as the organochlorine pesticides,
      which are often found in undesired places. In this work, we show that a hybrid
      nanomaterial (laccase-MSU-F) readily oxidizes the pesticide dichlorophen,
      reducing its acute genotoxicity and apoptotic effects. In order to predict
      chronic alterations related to endocrine disruption, we compared the calculated
      affinity of dichlorophen oxidized subproducts to steroid hormone nuclear
      receptors (NRs), using molecular simulation methods. We found a reduction in
      theoretical affinity of subproducts of oxidized dichlorophen for the ligand
      binding pocket of NRs (~5 kcal/mol), likewise of changes in binding modes, that
      suggests a reduction in binding events (RMSD values < 10 A).

PMID- 29337541
TI  - Enzyme Architecture: The Role of a Flexible Loop in Activation of Glycerol-3
      phosphate Dehydrogenase for Catalysis of Hydride Transfer.
AB  - The side chain of Q295 of glycerol-3-phosphate dehydrogenase from human liver (
      hlGPDH) lies in a flexible loop, that folds over the phosphodianion of substrate
      dihydroxyacetone phosphate (DHAP). Q295 interacts with the side-chain cation from
      R269, which is ion-paired to the substrate phosphodianion. Kinetic parameters
      kcat/ Km (M-1 s-1) and kcat/ KGA KHPi (M-2 s-1) were determined, respectively,
      for catalysis of the reduction of DHAP and for dianion activation of catalysis of
      reduction of glycolaldehyde (GA) catalyzed by wild-type, Q295G, Q295S, Q295A, and
      Q295N mutants of hlGPDH. These mutations result in up to a 150-fold decrease in (
      kcat/ Km)DHAP and up to a 2.7 kcal/mol decrease in the intrinsic phosphodianion
      binding energy. The data define a linear correlation with slope 1.1, between the
      intrinsic phosphodianion binding energy and the intrinsic phosphite dianion
      binding energy for activation of hlGPDH-catalyzed reduction of GA, that
      demonstrates a role for Q295 in optimizing this dianion binding energy. The R269A
      mutation of wild-type GPDH results in a 9.1 kcal/mol destabilization of the
      transition state for reduction of DHAP, but the same R269A mutation of N270A and
      Q295A mutants result in smaller 5.9 and 4.9 kcal/mol transition-state
      destabilization. Similarly, the N270A or Q295A mutations of R269A GPDH each
      result in large falloffs in the efficiency of rescue of the R269A mutant by
      guanidine cation. We conclude that N270, which interacts for the substrate
      phosphodianion and Q295, which interacts with the guanidine side chain of R269,
      function to optimize the apparent transition-state stabilization provided by the
      cationic side chain of R269.

PMID- 29337542
TI  - A Domino Process toward Functionally Dense Quaternary Carbons through Pd
      Catalyzed Decarboxylative C(sp3)-C(sp3) Bond Formation.
AB  - An efficient protocol was developed to construct functionally dense quaternary
      carbons with concomitant formation of a new Csp3-Csp3 bond via Pd-catalyzed
      decarboxylative transformation of vinyl cyclic carbonates. This redox-neutral
      catalytic system features stereocontrolled formation of multisubstituted allylic
      scaffolds with an aldehyde functionality generated in situ, and it typically can
      be performed at room temperature without any additives. DFT calculations provide
      a rationale toward the selective formation of these compounds and reveal a
      complex mechanism that with the help of microkinetic models is able to reproduce
      the nontrivial dependence of the identity of the product on the nature of the
      substituents in the substrate.

PMID- 29337544
TI  - Pushing up the Size Limit of Metal Chalcogenide Supertetrahedral Nanocluster.
AB  - The cubic ZnS structure type and the size-dependent properties of related
      nanoparticles are of both fundamental and technological importance. Yet, it
      remains a challenge to synthesize large atom-precise clusters of this structure
      type. Currently, only supertetrahedral clusters with 4, 10, 20, and 35 metal
      sites (denoted as T2, T3, T4, and T5, respectively) are known. Because the
      synthesis of T5 in 2002, numerous synthetic efforts targeting larger clusters
      only resulted in T2-T5 clusters in various compositions and intercluster
      connectivity, with T6 (56 metal and 84 anion sites) being elusive. Here, we
      report the so-far largest supertetrahedral cluster (T6, [Zn25In31S84]25-). New T6
      clusters can serve as the host matrix for optically active centers. Mn-doped
      variants of T4 and T6 have also been made, allowing the investigation of site
      dependent Mn emission. The results lead to the elucidation of the mechanism
      regulating Mn emission via size-dependent crystal lattice strain and provide new
      insight into Mn-doping chemistry in cluster-based chalcogenides at the atomic
      level.

PMID- 29337545
TI  - Donor Engineering for NIR-II Molecular Fluorophores with Enhanced Fluorescent
      Performance.
AB  - Organic fluorophores have been widely used for biological imaging in the visible
      and the first near-infrared windows. However, their application in the second
      near-infrared window (NIR-II, 1000-1700 nm) is still limited mainly due to low
      fluorescence quantum yields (QYs). Here, we explore molecular engineering on the
      donor unit to develop high performance NIR-II fluorophores. The fluorophores are
      constructed by a shielding unit-donor(s)-acceptor-donor(s)-shielding unit
      structure. Thiophene is introduced as the second donor connected to the shielding
      unit, which can increase the conjugation length and red-shift the fluorescence
      emission. Alkyl thiophene is employed as the first donor connected to the
      acceptor unit. The bulky and hydrophobic alkyl thiophene donor affords larger
      distortion of the conjugated backbone and fewer interactions with water molecules
      compared to other donor units studied before. The molecular fluorophore IR-FTAP
      with octyl thiophene as the first donor and thiophene as the second donor
      exhibits fluorescence emission peaked at 1048 nm with a QY of 5.3% in aqueous
      solutions, one of the highest for molecular NIR-II fluorophore reported so far.
      Superior temporal and spatial resolutions have been demonstrated with IR-FTAP
      fluorophore for NIR-II imaging of the blood vessels of a mouse hindlimb.

PMID- 29337547
TI  - Calix[n]arene-Catalyzed Three-Component Povarov Reaction: Microwave-Assisted
      Synthesis of Julolidines and Mechanistic Insights.
AB  - A new one-pot cascade reaction-based application of Povarov reactions with a p
      sulfonic acid calix[4]arene catalyst for the synthesis of a series of 34
      julolidine derivatives with substituents at C8 or C9 in good to excellent yields
      is reported. These microwave-assisted reactions proceeded efficiently, had short
      reaction times, were metal-free, were low cost, and used an inexpensive, easily
      available and nontoxic catalyst. These advantages, along with a simple workup
      procedure, make this protocol a very efficient and green alternative to the
      traditional methods for constructing these types of N-heterocyclic skeletons. In
      addition, this protocol allows the formation of julolidine structures, which
      requires the construction of four new C-C bonds and two C-N bonds. A mechanism
      for the Povarov reaction involving a stepwise sequence via ionic intermediates
      was proposed and validated.

PMID- 29337543
TI  - Bright Side of Lignin Depolymerization: Toward New Platform Chemicals.
AB  - Lignin, a major component of lignocellulose, is the largest source of aromatic
      building blocks on the planet and harbors great potential to serve as starting
      material for the production of biobased products. Despite the initial challenges
      associated with the robust and irregular structure of lignin, the valorization of
      this intriguing aromatic biopolymer has come a long way: recently, many creative
      strategies emerged that deliver defined products via catalytic or biocatalytic
      depolymerization in good yields. The purpose of this review is to provide insight
      into these novel approaches and the potential application of such emerging new
      structures for the synthesis of biobased polymers or pharmacologically active
      molecules. Existing strategies for functionalization or defunctionalization of
      lignin-based compounds are also summarized. Following the whole value chain from
      raw lignocellulose through depolymerization to application whenever possible,
      specific lignin-based compounds emerge that could be in the future considered as
      potential lignin-derived platform chemicals.

PMID- 29337546
TI  - A Mitochondria-Specific Fluorescent Probe for Visualizing Endogenous Hydrogen
      Cyanide Fluctuations in Neurons.
AB  - An ability to visualize HCN in mitochondria in real time may permit additional
      insights into the critical toxicological and physiological roles this classic
      toxin plays in living organisms. Herein, we report a mitochondria-specific
      coumarin pyrrolidinium-derived fluorescence probe (MRP1) that permits the real
      time ratiometric imaging of HCN in living cells. The response is specific,
      sensitive (detection limit is ca. 65.6 nM), rapid (within 1 s), and reversible.
      Probe MRP1 contains a benzyl chloride subunit designed to enhance retention
      within the mitochondria under conditions where the mitochondria membrane
      potential is eliminated. It has proved effective in visualizing different
      concentrations of exogenous HCN in the mitochondria of HepG2 cells, as well as
      the imaging of endogenous HCN in the mitochondria of PC12 cells and within
      neurons. Fluctuations in HCN levels arising from the intracellular generation of
      HCN could be readily detected.

PMID- 29337548
TI  - RE[N(SiMe3)2]3-Catalyzed Guanylation/Cyclization of Amino Acid Esters and
      Carbodiimides.
AB  - The example of rare-earth metal-catalyzed guanylation/cyclization of amino acid
      esters and carbodiimides is well-established, forming 4(3H)-2
      alkylaminoquinazolinones in 65-96% yields. The rare-earth metal amides
      RE[N(TMS)2]3 (RE = Y, Yb, Nd, Sm, La; TMS = SiMe3) showed high activities, and
      La[N(TMS)2]3 performed best for a wide scope of the substrates.

PMID- 29337549
TI  - Increasing the Ambient Pressure Solubility by Forming a Glass at High Pressure
      and Its Thermodynamics, a Much Sought-After Pharmaceutical Advantage.
AB  - With the objective of increasing the bioavailability of poorly soluble curative
      compounds, we describe a thermodynamics-based method for increasing their
      solubility, sigma. It requires forming their pressure-densified glassy (PDG)
      state by supercooling the melt under a high pressure to form glass,
      depressurizing, and recovering the glass at a low temperature. First, we formally
      show that the excess free energy of PDG is higher at ambient pressure than that
      of a glass (normally) formed by supercooling the melt at ambient pressure (NG),
      and therefore its sigma will be higher. For a given compound, sigma would
      increase with the pressure under which the liquid is cooled to form PDG and also
      with increase in the cooling rate. Second, we propose that this increase may be
      determined by using differential scanning calorimetry heating scans and, more
      accurately and directly, by vapor pressure measurement. Analysis of calorimetry
      data of poly(styrene) shows that the magnitude of increase in sigma is
      considerable and is expected to be much higher for curative compounds. Since
      sigma is related to vapor pressure through the free energy change, and to the
      dissolution rate, Gamma, the PDG state a compound would not only sublimate
      rapidly but also dissolve rapidly. We discuss the stability of PDG relative to NG
      against structural relaxation and crystallization and, hence, of their
      bioavailability with time.

PMID- 29337550
TI  - Palladium-Catalyzed Oxidative Cross-Coupling of Arylhydrazines and Arenethiols
      with Molecular Oxygen as the Sole Oxidant.
AB  - A highly efficient palladium-catalyzed oxidative cross-coupling of arylhydrazines
      and arenethiols with molecular oxygen as the sole oxidant to afford unsymmetrical
      diaryl sulfides has been developed. The only byproducts are nitrogen and water. A
      broad range of functional groups, even the reactive iodides, are tolerated and
      thus offer the opportunity for further functionalization.

PMID- 29337551
TI  - Synthesis of Polycyclic delta-Lactams with Bridged Benzomorphan Skeleton:
      Selectivity and Diversity Driven by Substituents.
AB  - An efficient synthesis of bromofunctionalized 2,6-methano- and 1,5-methano
      benzomorphanones, starting from easily available 6-benzyl-3,6-dihydropyridin
      2(1H)-ones, is described. Furthermore, the synthesis of bridged benzomorphanones
      with hitherto not known polycyclic systems containing 2- or 3
      azabicyclo[4.1.0]heptane units is developed upon treatment of both 2,6- and 1,5
      methanobromobenzomorphans with t-BuOK. The effects of substituents on the
      diversity and stereoselectivity of both transformations are studied.

PMID- 29337552
TI  - Molecular Dynamics Simulations of the Oil-Detachment from the Hydroxylated Silica
      Surface: Effects of Surfactants, Electrostatic Interactions, and Water Flows on
      the Water Molecular Channel Formation.
AB  - The detachment process of an oil molecular layer situated above a horizontal
      substrate was often described by a three-stage process. In this mechanism, the
      penetration and diffusion of water molecules between the oil phase and the
      substrate was proposed to be a crucial step to aid in removal of oil layer/drops
      from substrate. In this work, the detachment process of a two-dimensional alkane
      molecule layer from a silica surface in aqueous surfactant solutions is studied
      by means of molecular dynamics (MD) simulations. By tuning the polarity of model
      silica surfaces, as well as considering the different types of surfactant
      molecules and the water flow effects, more details about the formation of water
      molecular channel and the expansion processes are elucidated. It is found that
      for both ionic and nonionic type surfactant solutions, the perturbation of
      surfactant molecules on the two-dimensional oil molecule layer facilitates the
      injection and diffusion of water molecules between the oil layer and silica
      substrate. However, the water channel formation and expansion speed is strongly
      affected by the substrate polarity and properties of surfactant molecules. First,
      only for the silica surface with relative stronger polarity, the formation of
      water molecular channel is observed. Second, the expansion speed of the water
      molecular channel upon the ionic surfactant (dodecyl trimethylammonium bromide,
      DTAB and sodium dodecyl benzenesulfonate, SDBS) flooding is more rapidly than the
      nonionic surfactant system (octylphenol polyoxyethylene(10) ether, OP-10). Third,
      the water flow speed may also affect the injection and diffusion of water
      molecules. These simulation results indicate that the water molecular channel
      formation process is affected by multiple factors. The synergistic effects of
      perturbation of surfactant molecules and the electrostatic interactions between
      silica substrate and water molecules are two key factors aiding in the injection
      and diffusion of water molecules and helpful for the oil detachment from silica
      substrate.

PMID- 29337553
TI  - Selective Construction of 2-Substituted Benzothiazoles from o-Iodoaniline
      Derivatives S8 and N-Tosylhydrazones.
AB  - Selective construction of 2-substituted benzothiazoles from o-iodoaniline
      derivatives S8 and N-tosylhydrazone via a copper-promoted [3 + 1 + 1]-type
      cyclization reaction has been realized. In the protocol, the carbon atom on N
      tosylhydrazone could be regulated to construct benzothiazole by changing the
      reaction system. Furthermore, the transformation has achieved the construction of
      multiple carbon-heteroatom bonds.

PMID- 29337554
TI  - Light-Induced Deformation of Azobenzene-Containing Colloidal Spheres: Calculation
      and Measurement of Opto-Mechanical Stresses.
AB  - We report on light-induced deformation of colloidal spheres consisting of
      azobenzene-containing polymers. The colloids of the size between 60 nm and 2 MUm
      in diameter were drop casted on a glass surface and irradiated with linearly
      polarized light. It was found that colloidal particles can be deformed up to ca.
      6 times of their initial diameter. The maximum degree of deformation depends on
      the irradiation wavelength and intensity, as well as on colloidal particles size.
      On the basis of recently proposed theory by Toshchevikov et al. [ J. Phys. Chem.
      Lett. 2017 , 8 , 1094 ], we calculated the opto-mechanical stresses (ca. 100 MPa)
      needed for such giant deformations and compared them with the experimental
      results.

PMID- 29337555
TI  - Reconsideration of the Detection and Fluorescence Mechanism of a Pyrene-Based
      Chemosensor for TNT.
AB  - The rapid detection of chemical explosives is crucial for national security and
      public safety, and the investigation of sensing mechanisms is important for
      designing highly efficient chemosensors. This study theoretically investigates
      the detection and fluorescence mechanism of a newly synthesized pyrene-based
      chemosensor for the detection of trinitrotoluene (TNT) through density-functional
      theory (DFT) and time-dependent density-functional-theory (TDDFT) methods and
      suggests a different interaction product of the probe and TNT from previously
      reported ones [ Mosca et al. J. Am. Chem. Soc. 2015 , 137 , 7967 ]. Instead of
      forming Meisenheimer complexes, the energies of which are beyond those of the
      reactants, a low-energy product generated by a pi-pi-stacking interaction is more
      rational and favorable. The fluorescence-quenching property further confirms that
      the pi-pi-stacking product is the predicted one rather than luminescent
      Meisenheimer complexes. Frontier-molecular-orbital (FMO)-analysis results show
      that photoinduced electron transfer (PET) is the mechanism underlying the
      luminescence quenching of the probe upon exposure to TNT.

PMID- 29337556
TI  - Organocatalyzed Asymmetric Vinylogous Addition of Oxazole-2(3H)-thiones to
      alpha,beta-Unsaturated Ketones: An Additive-Free Approach for Diversification of
      Heterocyclic Scaffold.
AB  - A straightforward organocatalyzed asymmetric addition of oxazole-2(3H)-thiones to
      alpha,beta-unsaturated ketones is described. This additive-free Michael reaction
      in the presence of chiral cinchonine-derived primary amines as catalysts has
      proven to be highly effective for a wide range of cyclic and acyclic enones,
      leading to the Michael adducts in very good yields and excellent
      enantioselectivities. The absolute configuration (R) of compound 5j was
      unambiguously assigned by X-ray diffraction analysis. Furthermore, experimental
      and theoretical studies were performed and a mechanism is presented and discussed
      for this novel reaction.

PMID- 29337557
TI  - Pair Interaction Energy Decomposition Analysis for Density Functional Theory and
      Density-Functional Tight-Binding with an Evaluation of Energy Fluctuations in
      Molecular Dynamics.
AB  - Pair interaction energy decomposition analysis in the fragment molecular orbital
      (FMO) method is extended to treat density functional theory (DFT) and density
      functional tight-binding (DFTB). Fluctuations of energy contributions are
      obtained from molecular dynamics simulations. Interactions at the DFT and DFTB
      levels are compared to the values obtained with Hartree-Fock, second-order Moller
      Plesset (MP2), and coupled cluster methods. Hydrogen bonding in water clusters is
      analyzed. 200 ps NVT molecular dynamics simulations are performed with FMO for
      two ligands bound to the Trp-cage miniprotein (PDB 1L2Y ); the fluctuations of
      fragment energies and interactions are analyzed.

PMID- 29337558
TI  - Spatial Isolation of Conformational Isomers of Hydroquinone and Its Water Cluster
      Using the Stark Deflector.
AB  - Conformational isomers of hydroquinone and their 1:1 clusters with water have
      been spatially separated using a Stark deflector in a supersonic jet. trans
      Hydroquinone (HyQ) conformer with zero dipole moment is little influenced by
      inhomogeneous electric fields, whereas cis conformer with nonzero dipole moment
      (2.38 D) is significantly deflected from the molecular beam axis into the
      direction along which the strong field gradient is applied. Resonant two photon
      ionization carried out by shifting the laser position perpendicular to the
      molecular beam axis after the Stark deflector then gives an exclusive S1-S0
      excitation spectrum of the cis conformer only, making possible immaculate
      conformer-specific spectroscopy and dynamics. As the spatial separation is
      apparently proportional to the effective dipole moment strength, conformational
      assignment could be absolute in the Stark deflector, which contrasts with the
      hole-burning spectroscopic technique where identification of a conformational
      isomer is intrinsically not unambiguous. trans- and cis-HyQ-H2O clusters have
      also been spatially separated according to their distinct effective dipole moment
      strengths to give absolute spectroscopic identification of each cluster isomer,
      nailing down the otherwise disputable conformational assignment. This is the
      first report for the spatial separation of conformational cluster isomers.

PMID- 29337559
TI  - Totally Organic Redox-Active pH-Sensitive Nanoparticles Stabilized by Amphiphilic
      Aromatic Polyketones.
AB  - Amphiphilic aromatic polymers have been synthesized by grafting aliphatic
      polyketones with 4-(aminomethyl)benzoic acid at different molar ratios via the
      Paal-Knorr reaction. The resulting polymers, showing diketone conversion degree
      of 16%, 37%, 53%, and 69%, have been complexed with the redox-active 2,3,5
      triphenyl-2H-tetrazolium chloride, a precursor molecule with which aromatic
      aromatic interactions are held. Upon addition of ascorbic acid to the complexes,
      in situ reduction of the tetrazolium salt produced 1,3,5-triphenylformazan
      nanoparticles stabilized by the amphiphilic polymers. The stabilized
      nanoparticles display highly negative zeta potential [-(35-70) mV] and
      hydrodynamic diameters in the submicron range (100-400 nm). Nonaromatic
      polyelectrolytes or hydrophilic aromatic copolymers showing low linear aromatic
      density and high linear charge density such as acrylate/maleate and
      sulfonate/maleate-containing polymers were unable to stabilize formazan
      nanoparticles synthesized by the same method. The copolymers studied here bear
      uncharged nonaromatic comonomers (unreacted diketone units) as well as charged
      aromatic comonomers, which furnish amphiphilia. Thus, the linear aromatic density
      and the maximum linear charge density have the same value for each copolymer, and
      the hydrophilic/hydrophobic balance varies with the diketone conversion degree.
      The amphiphilia of the copolymers allows the stabilization of the nanoparticles,
      even with the copolymers showing a low linear aromatic density. The method of
      nanoparticle synthesis constitutes a simple, cheap, and green method for the
      production of switchable totally organic, redox-active, pH-sensitive
      nanoparticles that can be reversibly turned into macroprecipitates upon pH
      changing.

PMID- 29337560
TI  - Visible Light-Promoted Three-Component Tandem Annulation for the Synthesis of 2
      Iminothiazolidin-4-ones.
AB  - Described is a visible light-promoted three-component tandem annulation of
      amines, aryl/alkyl isothiocyanates, and alpha-bromoesters to form 2
      iminothiazolidin-4-ones in the absence of metal and photocatalyst at room
      temperature. This [1 + 2 + 2] cyclization strategy involves visible light
      promoted C-S/C-N bond formation and features a powerful approach to the synthesis
      of 2-iminothiazolidin-4-ones with broad substrate scope, excellent functional
      group tolerance, mild reaction conditions, step-economy, and simple operation,
      which also has potential applications in the pharmaceutical industry. UV-vis
      spectroscopy indicates that an in situ-generated H-bonding electron donor
      acceptor (EDA) complex probably acts as the photocatalyst, facilitating the
      reaction process.

PMID- 29337561
TI  - Methylammonium Cation Dynamics in Methylammonium Lead Halide Perovskites: A Solid
      State NMR Perspective.
AB  - In light of the intense recent interest in the methylammonium lead halides,
      CH3NH3PbX3 (X = Cl, Br, and I) as sensitizers for photovoltaic cells, the
      dynamics of the methylammonium (MA) cation in these perovskite salts has been
      reinvestigated as a function of temperature via 2H, 14N, and 207Pb NMR
      spectroscopy. In the cubic phase of all three salts, the MA cation undergoes
      pseudoisotropic tumbling (picosecond time scale). For example, the correlation
      time, tau2, for the C-N axis of the iodide salt is 0.85 +/- 0.30 ps at 330 K. The
      dynamics of the MA cation are essentially continuous across the cubic <->
      tetragonal phase transition; however, 2H and 14N NMR line shapes indicate that
      subtle ordering of the MA cation occurs in the tetragonal phase. The temperature
      dependence of the cation ordering is rationalized using a six-site model, with
      two equivalent sites along the c-axis and four equivalent sites either
      perpendicular or approximately perpendicular to this axis. As the cubic <->
      tetragonal phase transition temperature is approached, the six sites are nearly
      equally populated. Below the tetragonal <-> orthorhombic phase transition, 2H NMR
      line shapes indicate that the C-N axis is essentially frozen.

PMID- 29337562
TI  - Physiologically Based Pharmacokinetic Modeling in Lead Optimization. 2. Rational
      Bioavailability Design by Global Sensitivity Analysis To Identify Properties
      Affecting Bioavailability.
AB  - When medicinal chemists need to improve oral bioavailability (%F) during lead
      optimization, they systematically modify compound properties mainly based on
      their own experience and general rules of thumb. However, at least a dozen
      properties can influence %F, and the difficulty of multiparameter optimization
      for such complex nonlinear processes grows combinatorially with the number of
      variables. Furthermore, strategies can be in conflict. For example, adding a
      polar or charged group will generally increase solubility but decrease
      permeability. Identifying the 2 or 3 properties that most influence %F for a
      given compound series would make %F optimization much more efficient. We
      previously reported an adaptation of physiologically based pharmacokinetic (PBPK)
      simulations to predict %F for lead series from purely computational inputs within
      a 2-fold average error. Here, we run thousands of such simulations to generate a
      comprehensive "bioavailability landscape" for each series. A key innovation was
      recognition that the large and variable number of p Ka's in drug molecules could
      be replaced by just the two straddling the isoelectric point. Another was use of
      the ZINC database to cull out chemically inaccessible regions of property space.
      A quadratic partial least squares regression (PLS) accurately fits a continuous
      surface to these thousands of bioavailability predictions. The PLS coefficients
      indicate the globally sensitive compound properties. The PLS surface also
      displays the %F landscape in these sensitive properties locally around compounds
      of particular interest. Finally, being quick to calculate, the PLS equation can
      be combined with models for activity and other properties for multiobjective lead
      optimization.

PMID- 29337563
TI  - Magic-Angle Stacking and Strong Intermolecular pi-pi Interaction in a Perylene
      Bisimide Crystal: An Approach for Efficient Near-Infrared (NIR) Emission and High
      Electron Mobility.
AB  - A single crystal of N,N'-bis(4-methoxybenzyl)perylene-3,4,9,10-bis(dicarboximide)
      (mb-PBI) that possesses novel magic-angle stacking (M-type stacking) and strong
      intermolecular pi-pi interaction is achieved by physical vapor transport (PVT),
      which shows attractive optoelectronic functions such as efficient NIR emission
      and high electron mobility. In this special M-type staking, the strong Frenkel/CT
      mixing state promotes fluorescence and, importantly, the elimination of long
      distance Forster resonance energy transfer enables the minimization of the
      possible fluorescence quenching, which ensure the highly efficient emission.
      Moreover, the strong pi-pi interaction elongates the "supramolecular conjugation"
      to reduce the energy gap and also benefits the electron mobility of the crystal.
      The experimental results clearly indicate that M-type staking is a novel approach
      to optimize the optoelectronic functions of organic semiconducting materials.

PMID- 29337564
TI  - Vibrational Dynamics and Couplings of the Hydrated RNA Backbone: A Two
      Dimensional Infrared Study.
AB  - The equilibrium structure of the RNA sugar-phosphate backbone and its hydration
      shell is distinctly different from hydrated DNA. Applying femtosecond two
      dimensional infrared (2D-IR) spectroscopy in a range from 950 to 1300 cm-1, we
      elucidate the character, dynamics, and couplings of backbone modes of a double
      stranded RNA A-helix geometry in its aqueous environment. The 2D-IR spectra
      display a greater number of backbone modes than for DNA, with distinctly
      different lineshapes of diagonal peaks. Phosphate-ribose interactions and local
      hydration structures are reflected in the complex coupling pattern of RNA modes.
      Interactions with the fluctuating water shell give rise to spectral diffusion on
      a 300 fs time scale, leading to a quasi-homogeneous line shape of the symmetric
      (PO2)- stretching mode of the strongly hydrated phosphate groups. The RNA results
      are benchmarked by 2D-IR spectra of DNA oligomers in water and analyzed by
      molecular dynamics and quantum mechanical molecular mechanics simulations.

PMID- 29337565
TI  - Quantum Control of Graphene Plasmon Excitation and Propagation at Heaviside
      Potential Steps.
AB  - Quantum mechanical effects of single particles can affect the collective plasmon
      behaviors substantially. In this work, the quantum control of plasmon excitation
      and propagation in graphene is demonstrated by adopting the variable quantum
      transmission of carriers at Heaviside potential steps as a tuning knob. First,
      the plasmon reflection is revealed to be tunable within a broad range by varying
      the ratio gamma between the carrier energy and potential height, which originates
      from the quantum mechanical effect of carrier propagation at potential steps.
      Moreover, the plasmon excitation by free-space photos can be regulated from fully
      suppressed to fully launched in graphene potential wells also through adjusting
      gamma, which defines the degrees of the carrier confinement in the potential
      wells. These discovered quantum plasmon effects offer a unified quantum
      mechanical solution toward ultimate control of both plasmon launching and
      propagating, which are indispensable processes in building plasmon circuitry.

PMID- 29337566
TI  - Cationic Polymeric Nanoparticle Delivering CCR2 siRNA to Inflammatory Monocytes
      for Tumor Microenvironment Modification and Cancer Therapy.
AB  - Accumulating evidence has confirmed that malignant tumors have a complex
      microenvironment, which consists of a heterogeneous collection of tumor cells and
      other cell subsets (including the full gamut of immune cells). Tumor-associated
      macrophages (TAMs), derived from circulating Ly6Chi monocytes, constitute the
      most substantial fraction of tumor-infiltrating immune cells in nearly all cancer
      types and contribute to tumor progression, vascularization, metastasis,
      immunosuppression, and therapeutic resistance. Interrupting monocyte recruitment
      to tumor tissues by disturbing pivotal signaling pathways (such as CCL2-CCR2) is
      viewed as one of the most promising avenues for tumor microenvironment
      manipulation and cancer therapy. One critical issue for monocyte-based therapy is
      to deliver therapeutic agents into monocytes efficiently. In the present study,
      we systematically investigated the relationship between the surface potential and
      the biodistribution of polymeric nanoparticles in monocytes in vivo, aiming to
      screen and identify an appropriate delivery system for monocyte targeting, and we
      found that cationic nanoparticles have a higher propensity to accumulate in
      monocytes compared with their neutral counterparts. We further demonstrated that
      siCCR2-encapsulated cationic nanoparticle (CNP/siCCR2) could modify
      immunosuppressive tumor microenvironment more efficiently and exhibit superior
      antitumor effect in an orthotopic murine breast cancer model.

PMID- 29337567
TI  - Ultrafast Graphene Light Emitters.
AB  - Ultrafast electrically driven nanoscale light sources are critical components in
      nanophotonics. Compound semiconductor-based light sources for the nanophotonic
      platforms have been extensively investigated over the past decades. However,
      monolithic ultrafast light sources with a small footprint remain a challenge.
      Here, we demonstrate electrically driven ultrafast graphene light emitters that
      achieve light pulse generation with up to 10 GHz bandwidth across a broad
      spectral range from the visible to the near-infrared. The fast response results
      from ultrafast charge-carrier dynamics in graphene and weak electron-acoustic
      phonon-mediated coupling between the electronic and lattice degrees of freedom.
      We also find that encapsulating graphene with hexagonal boron nitride (hBN)
      layers strongly modifies the emission spectrum by changing the local optical
      density of states, thus providing up to 460% enhancement compared to the gray
      body thermal radiation for a broad peak centered at 720 nm. Furthermore, the hBN
      encapsulation layers permit stable and bright visible thermal radiation with
      electronic temperatures up to 2000 K under ambient conditions as well as
      efficient ultrafast electronic cooling via near-field coupling to hybrid
      polaritonic modes under electrical excitation. These high-speed graphene light
      emitters provide a promising path for on-chip light sources for optical
      communications and other optoelectronic applications.

PMID- 29337568
TI  - Rational Design of a Green-Light-Mediated Unimolecular Platform for Fast
      Switchable Acidic Sensing.
AB  - A controllable sensing ability strongly connects to complex and precise events in
      diagnosis and treatment. However, imposing visible light into the molecular-scale
      mediation of sensing processes is restricted by the lack of structural relevance.
      To address this critical challenge, we present the rational design, synthesis,
      and in vitro studies of a novel cyanostyryl-modified azulene system for green
      light-mediated fast switchable acidic sensing. The advantageous features of the
      design include a highly efficient green-light-driven Z/E-isomerization (a quantum
      yield up to 61.3%) for fast erasing chromatic and luminescent expressions and a
      superior compatibility with control of ratiometric protonation. Significantly,
      these merits of the design enable the development of a microfluidic system to
      perform a green-light-mediated reusable sensing function toward a gastric acid
      analyte in a miniaturized platform. The results may provide new insights for
      building future integrated green materials.

PMID- 29337569
TI  - Total Synthesis of the Highly N-Methylated Acetylene-Containing Anticancer
      Peptide Jahanyne.
AB  - The first total synthesis of the highly N-methylated acetylene-containing
      lipopeptide jahanyne, an apoptosis-inducing natural product from marine
      cyanobacteria, is reported. A late-stage solution-phase coupling enabled
      introduction of the C-terminal ketone pyrrolidine moiety. A modified Fmoc solid
      phase synthesis strategy was adopted to effectively couple multiple sterically
      hindered N-methylated amino acids while suppressing epimerization. The total
      synthesis has enabled confirmation of the proposed absolute configuration of
      natural jahanyne.

PMID- 29337570
TI  - Self-Organization of Metal Nanoparticles in Light: Electrodynamics-Molecular
      Dynamics Simulations and Optical Binding Experiments.
AB  - Light-driven self-organization of metal nanoparticles (NPs) can lead to unique
      optical matter systems, yet simulation of such self-organization (i.e., optical
      binding) is a complex computational problem that increases nonlinearly with
      system size. Here we show that a combined electrodynamics-molecular dynamics
      simulation technique can simulate the trajectories and predict stable
      configurations of silver NPs in optical fields. The simulated dynamic equilibrium
      of a two-NP system matches the probability density of oscillations for two
      optically bound NPs obtained experimentally. The predicted stable configurations
      for up to eight NPs are further compared to experimental observations of silver
      NP clusters formed by optical binding in a Bessel beam. All configurations are
      confirmed to form in real systems, including pentagonal clusters with five-fold
      symmetry. Our combined simulations and experiments have revealed a diverse
      optical matter system formed by anisotropic optical binding interactions,
      providing a new strategy to discover artificial materials.

PMID- 29337571
TI  - Direct Observation of a Transiently Formed Isomer During Iodoform Photolysis in
      Solution by Time-Resolved X-ray Liquidography.
AB  - Photolysis of iodoform (CHI3) in solution has been extensively studied, but its
      reaction mechanism remains elusive. In particular, iso-iodoform (iso-CHI2-I) is
      formed as a product of the photolysis reaction, but its detailed structure is not
      known, and whether it is a major intermediate species has been controversial.
      Here, by using time-resolved X-ray liquidography, we determined the reaction
      mechanism of CHI3 photodissociation in cyclohexane as well as the structure of
      iso-CHI2-I. Both iso-CHI2-I and CHI2 radical were found to be formed within 100
      ps with a branching ratio of 40:60. Iodine radicals (I), formed during the course
      of CHI3 photolysis, recombine nongeminately with either CHI2 or I. Based on our
      structural analysis, the I-I distance and the C-I-I angle of iso-CHI2-I were
      determined to be 2.922 +/- 0.004 A and 133.9 +/- 0.8 degrees , respectively.

PMID- 29337572
TI  - Plasmonic Horizon in Gold Nanosponges.
AB  - An electromagnetic wave impinging on a gold nanosponge coherently excites many
      electromagnetic hot-spots inside the nanosponge, yielding a polarization
      dependent scattering spectrum. In contrast, a hole, recombining with an electron,
      can locally excite plasmonic hot-spots only within a horizon given by the
      lifetime of localized plasmons and the speed carrying the information that a
      plasmon has been created. This horizon is about 57 nm, decreasing with increasing
      size of the nanosponge. Consequently, photoluminescence from large gold
      nanosponges appears unpolarized.

PMID- 29337573
TI  - Cryoprotectants Severely Exacerbate X-ray-Induced Photoreduction.
AB  - Approximately 11% of enzymes contain a transition metal ion that is essential for
      catalytic function. Such metalloenzymes catalyze much of the most chemically
      challenging and biologically essential chemistry carried out by life. X-ray-based
      methods, predominantly macromolecular crystallography (MX) and also X-ray
      absorption spectroscopy (XAS), have proved essential for determining structures
      of transition metal ion-containing active sites in order to deduce enzyme
      catalytic mechanisms. However, X-ray irradiation can induce change in both the
      oxidation state and structure of the metal, which is problematic in structure
      determination. We present an XAS study of whether cryoprotectants such as
      polyethylene glycol (PEG) or glycerol, routinely added to MX or XAS samples to
      improve data quality, affect photoreduction. Our data demonstrate a remarkable 10
      fold exacerbation in rate of photoreduction of Cu(II) to Cu(I) when alcohol or
      ether cryoprotectants are present. Our results suggest that widespread use of
      cryoprotectants may increase the potential for erroneous structures.

PMID- 29337574
TI  - Singlet Fission Mediated Photophysics of BODIPY Dimers.
AB  - The photodynamics of an orthogonal BODIPY dimer, particularly the formation of
      triplet states, has been explored by femtosecond and nanosecond transient
      absorption measurements. The short time scale data show the appearance of
      transient features of triplet character that, according to quantitative analysis
      of their intensities, account for more than 100% of the initially excited
      molecules, which reveals the occurrence of a singlet fission process in the
      isolated dimers. The formation rate of the triplet correlated state 1(TT) is
      found to depend on the solvent polarity, pointing to the mediation of a charge
      transfer character state. The dissociation of the 1(TT) state into pairs of
      individual triplets determines the triplet yield measured in the long time
      scales. The kinetic model derived from the results provides a comprehensive view
      of the photodynamics of BODIPY dimers and permits rationalization of the
      photophysical parameters of these systems.

PMID- 29337575
TI  - Optical Signatures of Impurity-Impurity Interactions in Copper Containing II-VI
      Alloy Semiconductors.
AB  - We study the optical properties of copper containing II-VI alloy quantum dots
      (CuxZnyCd1-x-ySe). Copper mole fractions within the host are varied from 0.001 to
      0.35. No impurity phases are observed over this composition range, and the
      formation of secondary phases of copper selenide are observed only at xCu > 0.45.
      The optical absorption and emission spectra of these materials are observed to be
      a strong function of xCu, and provide information regarding composition induced
      impurity-impurity interactions. In particular, the integrated cross section of
      optical absorption per copper atom changes sharply (from 1 * 10 -2 nm3 to 4 * 10 
      2 nm3) at xCu = 0.12, suggesting a composition induced change in local electronic
      structure. These materials may serve as model systems to understand the
      electronic structure of I-III-VI2 semiconductor compounds.

PMID- 29337576
TI  - Impact of Nanoporosity on Hydrocarbon Transport in Shales' Organic Matter.
AB  - In a context of growing attention for shale gas, the precise impact of organic
      matter (kerogen) on hydrocarbon recovery from unconventional reservoirs still has
      to be assessed. Kerogen's microstructure is characterized by a very disordered
      pore network that greatly affects hydrocarbon transport. The specific structure
      and texture of this organic matter at the nanoscale is highly dependent on its
      origin. In this study, by the use of statistical physics and molecular dynamics,
      we shed some new lights on hydrocarbon transport through realistic molecular
      models of kerogen at different level of maturity [ Bousige et al. Nat. Mater.
      2016 , 15 , 576 ]. Despite the apparent complexity, severe confinement effects
      controlled by the porosity of the various kerogens allow linear alkanes (from
      methane to dodecane) transport to be studied only via the self-diffusion
      coefficients of the species. The decrease of the transport coefficients with the
      amount of adsorbed fluid can be described by a free volume theory. Ultimately,
      the transport coefficients of hydrocarbons can be expressed simply as a function
      of the porosity (volume fraction of void) of the microstructure, thus paving the
      way for shale gas recovery predictions.

PMID- 29337577
TI  - Preparation of Nano Au and Pt Alloy Microspheres Decorated with Reduced Graphene
      Oxide for Nonenzymatic Hydrogen Peroxide Sensing.
AB  - The flourish of nanotechnology has brought new vitality to the research and
      development of electrochemical sensing materials. In this work, we successfully
      synthesized Nano Au and Pt alloy microspheres decorated with reduced graphene
      oxide (RGO/nAPAMSs) by a simple, facile, and eco-friendly one-step reduction
      strategy for the fabrication of highly sensitive nonenzymatic H2O2 sensing
      interfaces. Energy-dispersive X-ray spectroscopy mapping (EDX mapping), energy
      dispersive X-ray spectroscopy analysis (EDX), transmission electron microscopy
      (TEM), Fourier transform infrared spectrum (FT-IR), and X-ray diffraction
      spectrum (XRD) were employed to characterize RGO/nAPAMSs from a microscopic
      perspective. The results of cyclic voltammetry and chronoamperometry exhibited
      excellent electrochemical behaviors toward H2O2, with a rapid response time
      within 5 s, remarkable sensitivity of 1117.0 MUA mM-1 cm-2, wide linear range of
      0.005 to 4.0 mM and lower detection limit of 0.008 MUM (S/N = 3), which provide
      RGO/nAPAMS not only a promising prospect for the quantitative detection of H2O2
      but also a potential application in other fields of sensors. Moreover, further
      analysis showed the principles of the superior H2O2 sensing performance of
      RGO/nAPAMSs. This discovery provides a significant contribution to future study
      in nonenzymatic H2O2 sensing based on Nano Pt, Nano Au noble metal
      electrocatalysts.

PMID- 29337578
TI  - Physiologically Based Pharmacokinetic Modeling in Lead Optimization. 1.
      Evaluation and Adaptation of GastroPlus To Predict Bioavailability of Medchem
      Series.
AB  - When medicinal chemists need to improve bioavailability (%F) within a chemical
      series during lead optimization, they synthesize new series members with
      systematically modified properties mainly by following experience and general
      rules of thumb. More quantitative models that predict %F of proposed compounds
      from chemical structure alone have proven elusive. Global empirical %F
      quantitative structure-property (QSPR) models perform poorly, and projects have
      too little data to train local %F QSPR models. Mechanistic oral absorption and
      physiologically based pharmacokinetic (PBPK) models simulate the dissolution,
      absorption, systemic distribution, and clearance of a drug in preclinical species
      and humans. Attempts to build global PBPK models based purely on calculated
      inputs have not achieved the <2-fold average error needed to guide lead
      optimization. In this work, local GastroPlus PBPK models are instead customized
      for individual medchem series. The key innovation was building a local QSPR for a
      numerically fitted effective intrinsic clearance (CLloc). All inputs are
      subsequently computed from structure alone, so the models can be applied in
      advance of synthesis. Training CLloc on the first 15-18 rat %F measurements gave
      adequate predictions, with clear improvements up to about 30 measurements, and
      incremental improvements beyond that.

PMID- 29337579
TI  - Unveiling the Shape Evolution and Halide-Ion-Segregation in Blue-Emitting
      Formamidinium Lead Halide Perovskite Nanocrystals Using an Automated Microfluidic
      Platform.
AB  - Hybrid organic-inorganic perovskites and in particular formamidinium lead halide
      (FAPbX3, X = Cl, Br, I) perovskite nanocrystals (NCs) have shown great promise
      for their implementation in optoelectronic devices. Specifically, the Br and I
      counterparts have shown unprecedented photoluminescence properties, including
      precise wavelength tuning (530-790 nm), narrow emission linewidths (<100 meV) and
      high photoluminescence quantum yields (70-90%). However, the controlled formation
      of blue emitting FAPb(Cl1-xBrx)3 NCs lags behind their green and red counterparts
      and the mechanism of their formation remains unclear. Herein, we report the
      formation of FAPb(Cl1-xBrx)3 NCs with stable emission between 440 and 520 nm in a
      fully automated droplet-based microfluidic reactor and subsequent reaction
      upscaling in conventional laboratory glassware. The thorough parametric screening
      allows for the elucidation of parametric zones (FA-to-Pb and Br-to-Cl molar
      ratios, temperature, and excess oleic acid) for the formation of nanoplatelets
      and/or NCs. In contrast to CsPb(Cl1-xBrx)3 NCs, based on online parametric
      screening and offline structural characterization, we demonstrate that the
      controlled synthesis of Cl-rich perovskites (above 60 at% Cl) with stable
      emission remains a challenge due to fast segregation of halide ions.

PMID- 29337580
TI  - Spatiotemporal Control of Pre-existing Alkene Geometry: A Bio-Inspired Route to 4
      Trifluoromethyl-2H-chromenes.
AB  - Routes to prepare C4-trifluoromethyl analogues of the 2H-chromene scaffold are
      scarce: this is particularly striking given the importance of fluorine in
      pharmaceutical development. To address this limitation, a facile strategy has
      been developed that is reliant on catalytic, geometric isomerization of easily
      accessible allylic alcohols (up to >95:5) followed by intramolecular cyclization
      via Pd catalysis (up to 96%). This concise biomimetic approach emulates the
      photoisomerization/cyclization cascade inherent to phenylpropanoid biosynthesis.

PMID- 29337581
TI  - Light Harvesting by Equally Contributing Mechanisms in a Photosynthetic Antenna
      Protein.
AB  - We report supramolecular quantum mechanics/molecular mechanics simulations on the
      peridinin-chlorophyll a protein (PCP) complex from the causative algal species of
      red tides. These calculations reproduce for the first time quantitatively the
      distinct peridinin absorptions, identify multichromophoric molecular excitations,
      and elucidate the mechanisms regulating the strongly allowed S0 (11Ag-) -> S2
      (11Bu+) absorptions of the bound peridinins that span a 58 nm spectral range in
      the region of maximal solar irradiance. We discovered that protein binding site
      imposed conformations, local electrostatics, and electronic coupling contribute
      equally to the spectral inhomogeneity. Electronic coupling causes coherent
      excitations among the densely packed pigments. Complementary pairing of tuning
      mechanisms is the result of a competition between pigment-pigment and pigment
      environment interactions. We found that the aqueous solvent works in concert with
      the charge distribution of PCP to produce a strong correlation between peridinin
      spectral bathochromism and the local dielectric environment.

PMID- 29337582
TI  - Perceiving groups: The people perception of diversity and hierarchy.
AB  - The visual perception of individuals has received considerable attention (visual
      person perception), but little social psychological work has examined the
      processes underlying the visual perception of groups of people (visual people
      perception). Ensemble-coding is a visual mechanism that automatically extracts
      summary statistics (e.g., average size) of lower-level sets of stimuli (e.g.,
      geometric figures), and also extends to the visual perception of groups of faces.
      Here, we consider whether ensemble-coding supports people perception, allowing
      individuals to form rapid, accurate impressions about groups of people. Across
      nine studies, we demonstrate that people visually extract high-level properties
      (e.g., diversity, hierarchy) that are unique to social groups, as opposed to
      individual persons. Observers rapidly and accurately perceived group diversity
      and hierarchy, or variance across race, gender, and dominance (Studies 1-3).
      Further, results persist when observers are given very short display times,
      backward pattern masks, color- and contrast-controlled stimuli, and absolute
      versus relative response options (Studies 4a-7b), suggesting robust effects
      supported specifically by ensemble-coding mechanisms. Together, we show that
      humans can rapidly and accurately perceive not only individual persons, but also
      emergent social information unique to groups of people. These people perception
      findings demonstrate the importance of visual processes for enabling people to
      perceive social groups and behave effectively in group-based social interactions.
      (PsycINFO Database Record

PMID- 29337583
TI  - Sudden-death aversion: Avoiding superior options because they feel riskier.
AB  - We present evidence of sudden-death aversion (SDA)-the tendency to avoid "fast"
      strategies that provide a greater chance of success, but include the possibility
      of immediate defeat, in favor of "slow" strategies that reduce the possibility of
      losing quickly, but have lower odds of ultimate success. Using a combination of
      archival analyses and controlled experiments, we explore the psychology behind
      SDA. First, we provide evidence for SDA and its cost to decision makers by
      tabulating how often NFL teams send games into overtime by kicking an extra point
      rather than going for the 2-point conversion (Study 1) and how often NBA teams
      attempt potentially game-tying 2-point shots rather than potentially game-winning
      3-pointers (Study 2). To confirm that SDA is not limited to sports, we
      demonstrate SDA in a military scenario (Study 3). We then explore two mechanisms
      that contribute to SDA: myopic loss aversion and concerns about "tempting fate."
      Studies 4 and 5 show that SDA is due, in part, to myopic loss aversion, such that
      decision makers narrow the decision frame, paying attention to the prospect of
      immediate loss with the "fast" strategy, but not the downstream consequences of
      the "slow" strategy. Study 6 finds that people are more pessimistic about a risky
      strategy that needn't be pursued (opting for sudden death) than the same strategy
      that must be pursued. We end by discussing how these twin mechanisms lead to
      differential expectations of blame from the self and others, and how SDA
      influences decisions in several different walks of life. (PsycINFO Database
      Record

PMID- 29337584
TI  - Is antidepressant use associated with difficulty identifying feelings? A brief
      report.
AB  - Studies on the subjective effects of antidepressants suggest that they may not
      only improve depressed mood, but as an adverse effect also cause "emotional
      blunting." This phenomenon is poorly understood and little studied. The aim of
      this study was to examine the association of serotonergic antidepressant use and
      subjective emotional awareness. Emotional awareness was assessed using the
      Difficulty Identifying Feelings subscale from the 20-Item Toronto Alexithymia
      Scale. Fifty-seven individuals on antidepressant medication and 441 controls were
      compared. The effects of sex, age, education, as well as current depressive
      symptoms were controlled for. After controlling for selected variables, the
      antidepressant group scored higher in subjective difficulty identifying feelings,
      compared to controls. (p = .043, Adjusted means by Group 14.2 vs. 15.5, 95%
      confidence interval for mean difference between Groups 0.04-2.5). Serotonergic
      antidepressant use may be associated with difficulty identifying feelings. Future
      studies with a longitudinal setting are warranted to clarify causality. (PsycINFO
      Database Record

PMID- 29337585
TI  - Narrative theory: II. Self-generated and experimenter-provided negative income
      shock narratives increase delay discounting.
AB  - Reading experimenter-provided narratives of negative income shock has been
      previously demonstrated to increase impulsivity, as measured by discounting of
      delayed rewards. We hypothesized that writing these narratives would potentiate
      their effects of negative income shock on decision-making more than simply
      reading them. In the current study, 193 cigarette-smoking individuals from Amazon
      Mechanical Turk were assigned to either read an experimenter-provided narrative
      or self-generate a narrative describing either the negative income shock of job
      loss or a neutral condition of job transfer. Individuals then completed a task of
      delay discounting and measures of affective response to narratives, as well as
      rating various narrative qualities such as personal relevance and vividness.
      Consistent with past research, narratives of negative income shock increased
      delay discounting compared to control narratives. No significant differences
      existed in delay discounting after self-generating compared to reading
      experimenter-provided narratives. Positive affect was lower and negative affect
      was higher in response to narratives of job loss, but affect measures did not
      differ based on whether narratives were experimenter-provided or self-generated.
      All narratives were rated as equally realistic, but self-generated narratives
      (whether negative or neutral) were rated as more vivid and relevant than
      experimenter-provided narratives. These results indicate that the content of
      negative income shock narratives, regardless of source, consistently drives short
      term choices. (PsycINFO Database Record

PMID- 29337587
TI  - Use of lactic acid bacteria and yeasts to reduce exposure to chemical food
      contaminants and toxicity.
AB  - Chemical contaminants that are present in food pose a health problem and their
      levels are controlled by national and international food safety organizations.
      Despite increasing regulation, foods that exceed legal limits reach the market.
      In Europe, the number of notifications of chemical contamination due to pesticide
      residues, mycotoxins and metals is particularly high. Moreover, in many parts of
      the world, drinking water contains high levels of chemical contaminants owing to
      geogenic or anthropogenic causes. Elimination of chemical contaminants from water
      and especially from food is quite complex. Drastic treatments are usually
      required, which can modify the food matrix or involve changes in the forms of
      cultivation and production of the food products. These modifications often make
      these treatments unfeasible. In recent years, efforts have been made to develop
      strategies based on the use of components of natural origin to reduce the
      quantity of contaminants in foods and drinking water, and to reduce the quantity
      that reaches the bloodstream after ingestion, and thus, their toxicity. This
      review provides a summary of the existing literature on strategies based on the
      use of lactic acid bacteria or yeasts belonging to the genus Saccharomyces that
      are employed in food industry or for dietary purposes.

PMID- 29337586
TI  - Differential development of acute tolerance may explain heightened rates of
      impaired driving after consumption of alcohol mixed with energy drinks versus
      alcohol alone.
AB  - Consumers of alcohol mixed with energy drinks (AmED) are more likely to drive
      while impaired when compared to alcohol alone consumers. In addition, acute
      tolerance to the internal cues of feelings of intoxication is known to contribute
      to maladaptive decisions to drive while impaired. Therefore, the purpose of this
      study was to determine whether there is differential development of acute
      tolerance for AmED versus alcohol alone for ratings of willingness to drive after
      alcohol consumption. Social drinkers (n = 12) attended 4 separate sessions where
      they received alcohol and energy drinks, alone and in combination. The
      development of acute tolerance to alcohol was assessed for several objective (a
      computerized cued go/no-go reaction time task) and subjective measures at matched
      breath alcohol concentrations (BrACs) for the ascending and descending limbs of
      the BrAC curve. The results indicated that alcohol administration decreased
      willingness to drive ratings. Acute tolerance was observed in the AmED dose
      condition for only the willingness to drive ratings that were significantly
      higher on the descending versus ascending test. Alcohol-induced impairments of
      the computer task performance did not exhibit any acute tolerance. Therefore, the
      differential development of acute tolerance may explain why many studies observe
      higher rates of impaired driving for AmED consumers compared to alcohol alone
      consumers. Because drunk driving is a major public health concern, alcohol
      consumers should be warned that the use of energy drink mixers with alcohol could
      lead to a false sense of security in one's ability to drive after drinking.
      (PsycINFO Database Record

PMID- 29337588
TI  - An Argument for the Protocolized Screening and Management of Post-Extubation
      Stridor.

PMID- 29337589
TI  - Critical Review on the Analytical Mechanistic Steps in the Evaluation of
      Antioxidant Activity.
AB  - Electrophysiological systems are prone to release free radicals for functioning
      of biological system with proper balancing of antioxidant-prooxidant ratio for
      establishing a healthy living system. The biostress condition releases different
      reactive oxygen species, such as hydroxyl, alkoxyl, superoxide, hydrogen
      peroxide, hydroperoxyl, ozone, singlet oxygen, hypochlorus acid, thiyl radical,
      etc. This review tries to discuss the general aspects of the antioxidant assay
      methodologies that are currently used for the detection of antioxidant property.
      The entire review has been divided into three different sections. The first deals
      with the release of free radical by mitochondrial dysfuctioning and its curbing
      action by local antioxidants. The second and third sections discuss the general
      procedure adopted and reaction mechanism involved in the assay procedure along
      with the limitations and advantages.

PMID- 29337591
TI  - Reply to Smith et al.: An Argument for the Protocolized Screening and Management
      of Post-Extubation Stridor.

PMID- 29337590
TI  - Novel Mechanism for Nicotinamide Phosphoribosyltransferase Inhibition of TNF
      alpha-mediated Apoptosis in Human Lung Endothelial Cells.
AB  - Nicotinamide phosphoribosyltransferase (NAMPT) exists as both intracellular NAMPT
      and extracellular NAMPT (eNAMPT) proteins. eNAMPT is secreted into the blood and
      functions as a cytokine/enzyme (cytozyme) that activates NF-kappaB signaling via
      ligation of Toll-like receptor 4 (TLR4), further serving as a biomarker for
      inflammatory lung disorders such as acute respiratory distress syndrome. In
      contrast, intracellular NAMPT is involved in nicotinamide mononucleotide
      synthesis and has been implicated in the regulation of cellular apoptosis,
      although the exact mechanisms for this regulation are poorly understood. We
      examined the role of NAMPT in TNF-alpha-induced human lung endothelial cell (EC)
      apoptosis and demonstrated that reduced NAMPT expression (siRNA) increases EC
      susceptibility to TNF-alpha-induced apoptosis as reflected by PARP-1 cleavage and
      caspase-3 activation. In contrast, overexpression of NAMPT served to reduce
      degrees of TNF-alpha-induced EC apoptosis. Inhibition of nicotinamide
      mononucleotide synthesis by FK866 (a selective NAMPT enzymatic inhibitor) failed
      to alter TNF-alpha-induced human lung EC apoptosis, suggesting that NAMPT
      dependent NAD+ generation is unlikely to be involved in regulation of TNF-alpha
      induced EC apoptosis. We next confirmed that TNF-alpha-induced EC apoptosis is
      attributable to NAMPT secretion into the EC culture media and subsequent eNAMPT
      ligation of TLR4 on the EC membrane surface. Silencing of NAMPT expression,
      direct neutralization of secreted eNAMPT by an NAMPT-specific polyclonal antibody
      (preventing TLR4 ligation), or direct TLR4 antagonism all served to significantly
      increase EC susceptibility to TNF-alpha-induced EC apoptosis. Together, these
      studies provide novel insights into NAMPT contributions to lung inflammatory
      events and to novel mechanisms of EC apoptosis regulation.

PMID- 29337592
TI  - Concentrations of Blood Components in Commercial Platelet-Rich Plasma Separation
      Systems: A Review of the Literature.
AB  - BACKGROUND: Platelet-rich plasma (PRP) has proven to be a very safe therapeutic
      option in the treatment of tendon, muscle, bone, and cartilage injuries.
      Currently, several commercial separation systems are available for the
      preparation of PRP. The concentrations of blood components in PRP among these
      separation systems vary substantially. PURPOSE: To systematically review and
      evaluate the differences between the concentrations of blood components in PRP
      produced by various PRP separation systems. STUDY DESIGN: Systematic review.
      METHODS: MEDLINE/PubMed, the Cochrane Central Register of Controlled Trials
      (CENTRAL), and EMBASE were searched for studies that compared the concentrations
      of blood components and growth factors in PRP between various separation systems
      and studies that reported on the concentrations of blood components and growth
      factors of single separation systems. The primary outcomes were platelet count,
      leukocyte count, and concentration of growth factors (eg, platelet-derived growth
      factor-AB [PDGF-AB], transforming growth factor-beta1 [TGF-beta1], and vascular
      endothelial growth factor [VEGF]). Furthermore, the preparation protocols and
      prices of the systems were compared. RESULTS: There were 1079 studies found, of
      which 19 studies were selected for inclusion in this review. The concentrations
      of platelets and leukocytes in PRP differed largely between, and to a lesser
      extent within, the studied PRP separation systems. Additionally, large
      differences both between and within the studied PRP separation systems were found
      for all the growth factors. Furthermore, preparation protocols and prices varied
      widely between systems. CONCLUSION: There is a large heterogeneity between PRP
      separation systems regarding concentrations of platelets, leukocytes, and growth
      factors in PRP. The choice for the most appropriate type of PRP should be based
      on the specific clinical field of application. As the ideal concentrations of
      blood components and growth factors for the specific fields of application are
      yet to be determined for most of the fields, future research should focus on
      which type of PRP is most suitable for the specific field.

PMID- 29337593
TI  - Active December Caps Historic Year For Reform.
AB  - The month brought the repeal of the individual mandate's penalties, but also 2018
      enrollment numbers rivaling those of 2017.

PMID- 29337594
TI  - Solid Phase Microextraction Techniques in Determination of Biomarkers.
AB  - The detection and quantification of biomarkers is gaining attention in medical
      research and diagnostics communities. Biomarkers cover a range from gases to
      biological macromolecules. Because of the nanomolar range levels of typical
      biomarkers in plasma, blood, urine, exhalation samples, and other biological
      fluids as well as complex matrix of biological media, adequate sample preparation
      methods should be used for quantification of biomarkers. The performance of an
      analytical method for biomarkers should support reproducible and accurate data.
      In the present paper, recent progress in well-established solid phase
      microextraction (SPME) methods for the clinical analysis are reviewed and
      discussed.

PMID- 29337595
TI  - Outcome of extraocular retinoblastoma in a resource limited center from low
      middle income country.
AB  - Retinoblastoma (RB) is the most common ocular malignancy in children, and is
      managed by multimodal treatment. There is a paucity of data regarding the
      clinical profile and outcome of children with extraocular retinoblastoma from Low
      Middle Income Countries (LMIC) including India. Case records of children with
      newly diagnosed extraocular RB from January 2013 to August 2016 treated at our
      unit were analysed for clinical profile, treatment, and outcome. Over the 44
      month study period, 91 children were diagnosed with RB, out of which 41 had
      extraocular disease. While 26 children had extraocular spread limited to orbit
      (IRSS stage III), 15 had a distant spread to brain (IRSS stage IV). Median lag
      period for diagnosis was eight months. Treatment abandonment rates were 38.5% and
      46.6% in International Retinoblastoma Staging System (IRSS) stage III and IV
      respectively. With a median follow up of 31.5 months, the projected overall
      survival for IRSS III at one, two, and three years was 87.5%, 55.6%, and 39.7%.
      All patients with stage IV disease died after a median follow up duration of
      three months. High treatment abandonment rates and limited availability of
      resources lead to suboptimal survival in children with extraocular RB from LMIC.
      Initiatives aimed at improving early diagnosis, so that the disease is detected
      in the intraocular stage, are critical to improve the survival in children with
      RB.

PMID- 29337596
TI  - The Influence of Graft Fixation Methods on Revision Rates After Primary Anterior
      Cruciate Ligament Reconstruction.
AB  - BACKGROUND: The method of graft fixation in primary anterior cruciate ligament
      (ACL) reconstruction is important for initial stability of the graft. Poor graft
      fixation can result in failure of the reconstruction. The effect of ACL graft
      fixation principles and fixation implant combinations on the risk of revision
      after ACL reconstruction is not well understood. PURPOSE: The study aimed to
      compare the risk of revision among 4 categories of femoral fixation divided by
      their principle of function using a hamstring tendon (HT) graft only.
      Furthermore, this study aimed to compare the risk of revision among the most
      frequently used combinations (tibia and femur) of graft fixation implants in a
      national patient cohort. STUDY DESIGN: Cohort study; Level of evidence, 3.
      METHODS: The authors divided the femoral fixation constructs into 4 categories by
      their principle of function: cortical suspensory fixation, adjustable cortical
      suspensory fixation, intratunnel transfixation, and interference screw (aperture)
      fixation. Data on revision rates and graft fixation methods were extracted from
      the Danish ACL Reconstruction Registry. The study included patients who underwent
      primary ACL reconstruction with either an HT or patellar tendon (PT) graft and
      were followed up at 2 to 10 years. Revision rates at 2-year and full follow-up
      were extracted for the category of graft fixation in the femur as well as for the
      most common implant combinations (those involving >175 patients). Patients with
      infrequently used fixation devices were excluded from this analysis. The HT group
      included 14 frequently used combinations (n > 175), and there were 2 such
      combinations in the PT group. A total of 13,200 ACL reconstructions were included
      in the study. For ACL reconstruction with an HT graft, there were 4680 with
      cortical suspensory fixation, 577 with adjustable cortical suspensory fixation,
      5921 with intratunnel transfixation, and 617 with interference screw fixation.
      There were 1405 ACL reconstructions with a PT graft. RESULTS: When only comparing
      primary ACL reconstructions using an HT graft, cortical suspensory fixation
      exhibited a significantly higher risk of revision at 2-year follow-up than the
      other categories of femoral fixation (hazard ratio [HR], 1.24 [95% CI, 1.07
      1.44]; P < .05). Intratunnel transfixation exhibited a significantly lower risk
      of revision (HR, 0.83 [95% CI, 0.73-0.94]; P < .05). Comparing the most
      frequently used femoral/tibial fixation implant combinations with the mean risk
      of revision, Endobutton/Intrafix and Endobutton/Biosure PEEK for HT grafts
      exhibited an increased risk of revision, with an relative risk (RR) of 1.36 (95%
      CI, 1.03-1.81; P < .05) and 1.55 (95% CI, 1.15-2.09; P < .05), respectively. The
      Atlantech metal screw/metal screw and Softsilk/Softsilk combinations (both for PT
      grafts) exhibited a significantly decreased risk of revision, with an RR of 0.41
      (95% CI, 0.18-0.91; P < .05) and 0.36 (95% CI, 0.15-0.87; P < .05), respectively.
      CONCLUSION: When comparing ACL graft fixation methods in the 4 categories using
      an HT graft, cortical suspensory fixation was found to have a significantly
      increased risk of revision, while intratunnel transfixation exhibited a lower
      risk of revision. Both Endobutton/Intrafix and Endobutton/Biosure PEEK implant
      combinations exhibited a significantly higher risk of revision. For PT grafts,
      Atlantech metal screw/metal screw and Softsilk/Softsilk exhibited a significantly
      lower risk of revision.

PMID- 29337597
TI  - Hydroxyurea for lifelong transfusion-dependent beta-thalassemia: A meta-analysis.
AB  - OBJECTIVE: Chronic blood transfusion remains the most feasible therapeutic option
      for lifelong transfusion-dependent beta-thalassemia (lifelong TDbetaT). However,
      it is associated with serious risks and complications. Hydroxyurea (HU), an oral
      chemotherapeutic drug, is expected to increase hemoglobin levels, thereby
      minimizing the burden of blood transfusion and its complications. Growing
      literature over the last twenty years suggests promising results of the use HU in
      lifelong TDbetaT; however, its role and safety remain unanswered questions. The
      objective of this study was to evaluate the clinical efficacy and safety of HU in
      patients with lifelong TDbetaT. METHODS: MEDLINE, EMBASE, Cochrane databases, and
      major preceding conferences for studies that assessed HU in lifelong TDbetaT
      patients were searched. The effect size was estimated as a proportion
      (responder/sample size). RESULTS: Eleven observational studies, collectively
      involving 859 patients, fulfilled eligibility criteria. HU was associated with a
      significant decrease in transfusion need with complete and overall (>=50%)
      response rates of 26% [95% confidence interval (CI), 13-41%] and 60% (95% CI, 41
      78%), respectively. No serious adverse effects were reported. All of the studies
      had several limitations, such as lack of a comparison group. CONCLUSION: HU
      appears to be effective, well tolerated; however, large randomized clinical
      trials should be done to confirm such findings.

PMID- 29337598
TI  - Comparative Study of Intramedullary Hammertoe Fixation.
AB  - BACKGROUND: Temporary Kirschner wire fixation (K-wire) is a widely used, low-cost
      fixation method for the correction of hammertoe deformity. Reported complications
      associated with K-wires prompted the development of new implants over the past
      decade. However, there is a lack of literature on comparative studies analyzing
      functional outcomes using validated questionnaires. The purpose of this study was
      to analyze functional outcomes in patients who had undergone proximal
      interphalangeal joint fusion using 2 types of intramedullary implant, the Smart
      Toe and the TenFuse, and to compare them with the outcomes in patients treated
      with standard K-wire fixation. METHODS: A retrospective review of operative
      hammertoe correction by a single surgeon was performed in 96 patients followed
      for more than 12 months. Functional outcome was assessed using the Foot Function
      Index (FFI), the Short Form 36 (SF-36), and the 10-point visual analog scale
      (VAS) validated questionnaires. Complications and fusion rates were also
      evaluated. Several patients in the study underwent corrections in different toes;
      thus, a total of 186 toes were included in the study. From these, 65 toes (34.9%)
      were treated with K-wire fixation, 94 (50.5%) with Smart Toe titanium implant,
      and 27 (14.5%) with TenFuse allograft implant. RESULTS: No statistically
      significant differences in functional outcome and incidence of complications were
      observed among the 3 fixation groups, although the 2 intramedullary implants were
      associated with greater fusion rates and patient satisfaction. Breakage of the
      Smart Toe implant was significantly higher than that of the other fixations, with
      10.6% of implants breaking within the first year postoperatively. SF-36 and VAS
      scores decreased 12 months after surgery for the 3 types of fixation, with no
      statistically significant differences observed. CONCLUSION: The use of Smart Toe
      and TenFuse implants provided operative outcomes comparable to those obtained
      using a K-wire fixation and slightly better patient satisfaction. Our results
      suggest that utilization of these implants for hammertoe correction was a
      reasonable choice that provided good alignment, pain reduction, and improved
      function at final follow-up. However, they are more expensive than K-wires. For
      this reason, in-depth cost-benefit studies would be required to justify their use
      as a standard treatment. LEVEL OF EVIDENCE: Level III, comparative series.

PMID- 29337599
TI  - Pearson syndrome.
AB  - INTRODUCTION: Pearson syndrome (PS) is a sporadic and very rare syndrome
      classically associated with single large-scale deletions of mitochondrial DNA and
      characterized by refractory sideroblastic anemia during infancy. Areas covered:
      This review presents an analysis and interpretation of the published data that
      forms the basis for our understanding of PS. PubMed, Google Scholarand Thompson
      ISI Web of Knowledge were searched for relevant data. Expert commentary: PS is a
      very rare mitochodrial disease that involves different organs and systems.
      Clinical phenotype is extremely variable and may change over the course of
      disease itself with the possibility both of worsenings and improvements. Outcome
      is invariably lethal and at the moment no cure is available. Accurate supportive
      treatment and follow up program in centres with experience in mitochondrial
      diseases and marrow failure may positively influence quality and duration of
      life.

PMID- 29337600
TI  - Developing a theoretical foundation to change road user behavior and improve
      traffic safety: Driving under the influence of cannabis (DUIC).
AB  - OBJECTIVES: This study explored a theoretical model to assess the influence of
      culture on willingness and intention to drive under the influence of cannabis
      (DUIC). This model is expected to guide the design of strategies to change future
      DUIC behavior in road users. METHODS: This study used a survey methodology to
      obtain a nationally representative sample (n = 941) from the AmeriSpeak Panel.
      Survey items were designed to measure aspects of a proposed definition of traffic
      safety culture and a predictive model of its relationship to DUIC. RESULTS:
      Although the percentage of reported past DUIC behaviors was relatively low
      (8.5%), this behavior is still a significant public health issue-especially for
      younger drivers (18-29 years), who reported more DUIC than expected. Findings
      suggest that specific cultural components (attitudes, norms) reliably predict
      past DUIC behavior, general DUIC willingness, and future DUIC intention. Most
      DUIC behavior appears to be deliberate, related significantly to willingness and
      intention. Intention and willingness both appear to fully moderate the
      relationship between traffic safety culture and DUIC behavior. CONCLUSIONS: This
      study explored a theoretical model to understand road user behavior involving
      drug (cannabis)-impaired driving as a significant risk factor for traffic safety.
      By understanding the cultural factors that increase DUIC behavior, we can create
      strategies to transform this culture and sustain safer road user behavior.

PMID- 29337601
TI  - Mango kernel fat fractions as potential healthy food ingredients: A review.
AB  - Mango kernel fat (MKF) has been reported to have high functional and nutritional
      potential. However, its application in food industry has not been fully explored
      or developed. In this review, the chemical compositions, physical properties and
      potential health benefits of MKF are described. MKF is a unique fat consisting of
      28.9-65.0% of 1,3-distearoyl-2-oleoyl-glycerol with excellent oxidative stability
      index (58.8-85.2 h at 110  degrees C), making the fat and its fractions suitable
      for use as high-value added food ingredients such as cocoa butter alternatives,
      trans-free shortenings, and a source of natural antioxidants (e.g., sterol,
      tocopherol and squalene). Unfortunately, the long period of dehydration of mango
      kernels at hot temperature results in the hydrolysis of triacylglycerols. The
      high levels of hydrolysates (mainly free fatty acids and diacylglycerols) limit
      the application of MKF in manufacturing these food ingredients. It is suggested
      that the physico-chemical and functional properties of MKF could be further
      improved through moderated refining (e.g., degumming and physical
      deacidification), fractionation, and interesterification.

PMID- 29337602
TI  - Defining the Learning Curve for Hip Arthroscopy: A Threshold Analysis of the
      Volume-Outcomes Relationship.
AB  - BACKGROUND: Hip arthroscopy has emerged as a successful option for the treatment
      of femoroacetabular impingement and related hip disorders, but the procedure is
      technically challenging. PURPOSE: To define the learning curve through which
      surgeons become proficient at hip arthroscopy. STUDY DESIGN: Cohort study; level
      of evidence, 3. METHODS: The authors identified hip arthroscopy procedures
      performed by surgeons through a New York State database (Statewide Planning and
      Research Cooperative System) and followed those cases for additional hip surgery
      (total hip arthroplasty, hip resurfacing, or ipsilateral hip arthroscopy) within
      5 years of the original procedure. Career volume for each case was calculated as
      the number of hip arthroscopy procedures that the surgeon had performed. Volume
      strata were identified via the stratum-specific likelihood ratio method. A Cox
      proportional hazards model was used to measure the effect of surgeon career
      volume on risk of additional hip surgery, adjusting for the following patient
      characteristics: age, sex, race/ethnicity, insurance type, and concurrent
      diagnosis of hip osteoarthritis. RESULTS: Among 8041 hip arthroscopies performed
      by 251 surgeons, 989 (12.3%) cases underwent additional hip surgery within 5
      years. Four strata of surgeon career volume associated with distinct frequencies
      of reoperation were identified: cases in the lowest stratum (0-97) had the
      highest frequency of additional surgery (15.4%). Frequencies declined for cases
      in the medium (98-388), high (389-518), and highest (>=519) strata (13.8%, 10.1%,
      and 2.6%, respectively). There was an increased risk of subsequent surgery in
      each stratum when compared with the highest stratum (hazard ratio [95% CI]: low
      volume, 3.22 [2.29-4.54]; medium, 3.40 [2.41-4.82]; high, 2.81 [1.86-4.25]; P <
      .0001 for all). Patients with a diagnosis of hip osteoarthritis had increased
      risk of subsequent hip arthroplasty or resurfacing (2.46 [2.09-2.89], P < .0001)
      . Risk also increased with age: 30 to 39 vs <=29 years (5.12 [3.29-8.00], P <
      .0001), 40 to 49 vs <=29 years (11.30 [7.43-17.190], P < .0001), >=50 vs <=29
      years (18.39 [12.10-27.96], P < .0001). Increased age and osteoarthritis were not
      risk factors for revision hip arthroscopy. CONCLUSION: The learning curve for hip
      arthroscopy was unexpectedly demanding. Cases performed by surgeons with career
      volumes >=519 had significantly lower risk of subsequent hip surgery than those
      performed by lower-volume surgeons.

PMID- 29337603
TI  - An Integrative Review of Nonpharmacological Interventions to Improve Sleep among
      Adults with Advanced Serious Illness.
AB  - BACKGROUND: Sleep fragmentation is common among those with advanced serious
      illness. Nonpharmacological interventions to improve sleep have few, if any,
      adverse effects and are often underutilized in these settings. OBJECTIVE: We
      aimed to summarize the literature related to nonpharmacological interventions to
      improve sleep among adults with advanced serious illness. METHODS: We
      systematically searched six electronic databases for literature reporting sleep
      outcomes associated with nonpharmacological interventions that included
      participants with advanced serious illness during the period of 1996-2016.
      RESULTS: From a total of 2731 results, 42 studies met the inclusion criteria. A
      total of 31 individual interventions were identified, each evaluated individually
      and some in combination with other interventions. Twelve of these studies
      employed either multiple interventions within an intervention category (n = 8) or
      a multicomponent intervention consisting of interventions from two or more
      categories (n = 5). The following intervention categories emerged: sleep hygiene
      (1), environmental (6), physical activity (4), complementary health practices
      (11), and mind-body practices (13). Of the 42 studies, 22 demonstrated a
      statistically significant, positive impact on sleep and represented each of the
      categories. The quality of the studies varied considerably, with 17 studies
      classified as strong, 17 as moderate, and 8 as weak. CONCLUSIONS: Several
      interventions have been demonstrated to improve sleep in these patients. However,
      the small number of studies and wide variation of individual interventions within
      each category limit the generalizability of findings. Further studies are needed
      to assess interventions and determine effectiveness and acceptability.

PMID- 29337604
TI  - The Current Status of Outcomes-Based Contracting for Manufacturers and Payers: An
      AMCP Membership Survey.
AB  - BACKGROUND: As the United States health care system shifts from traditional
      volume-based payments to value-based payments, outcomes-based contracts (OBCs)
      are gaining popularity among payers and manufacturers as a mechanism for the
      shift toward value. Under this model, stakeholders hope to align drug payment and
      value to real-world performance metrics (e.g., biomarkers and health care
      resource utilization). OBJECTIVE: To understand the experiences, perceptions, and
      needs of payers and manufacturers related to OBCs. METHODS: The Academy of
      Managed Care Pharmacy (AMCP) and Xcenda conducted an online survey with AMCP
      payer and manufacturer members. Participants were asked a series of questions
      regarding their use of OBCs, barriers to implementation, and elements required in
      establishing successful OBCs. The importance and urgency of specific impediments
      to successful OBC implementation were also assessed. RESULTS: The survey was
      fielded May 12, 2017, to June 7, 2017, yielding 65 responses (35 payers/30
      manufacturers). While a minority of payers/manufacturers had at least 1 OBC in
      place (20%/33%), a majority had interest in future OBC use (71%/63%). Among those
      with at least 1 OBC in place, 86%/80% of payers/manufacturers had renewed at
      least 1 OBC in the past 5 years. All payers and 60% of manufacturers with OBCs
      included compliance measures. Improvement in clinical outcomes was also common
      (71%/70%) (e.g., reaching set laboratory values goals), and 71%/60% included
      avoidance of unnecessary medical resource use (e.g., hospitalization and
      emergency department visit). The barrier most frequently identified by payers in
      implementing OBCs was evidence that OBCs reduced pharmacy spending (60%), while
      manufacturers identified the inability to obtain accurate data/outcome measures
      (73%) as a major limiting factor. Payers/manufacturers endorsed the use of easily
      measurable outcomes (91%/100%) as most important in establishing successful OBCs.
      Manufacturers, and to a lesser extent payers, indicated that regulations and
      legal issues need to be addressed to make progress in OBC implementation (e.g.,
      safe harbor for preapproval health care economic information [77%/46%] and
      exemption of OBCs for best-price requirements [83%/51%]). The only exception was
      the clarification of regulations for discussing information outside of an FDA
      approved label, in which both manufacturers and payers indicated a very strong
      need (100%) to be addressed. CONCLUSIONS: Surveyed AMCP members are interested in
      OBCs and recognize their alignment to societal health goals and health care
      affordability, although actual use of these contracts has been somewhat limited
      to date. Results from this survey indicate that there is potential for OBC use to
      increase as barriers and limitations are addressed. DISCLOSURES: This research
      was sponsored by the Academy of Managed Care Pharmacy and Xcenda. Duhig, Kaufman,
      and Hughes are employed by Xcenda. Saha is employed by the Academy of Managed
      Care Pharmacy. Smith has nothing disclose. Study concept and design were
      contributed by Duhig, Kaufman, Saha, and Hughes. Kaufman and Hughes collected the
      data, and data interpretation was performed by all the authors. The manuscript
      was written by Saha, Smith, and Duhig, along with Kaufman and Hughes.

PMID- 29337606
TI  - Foodborne Pathogens and Disease Celebrates Its Fifteen Year Anniversary.

PMID- 29337605
TI  - Education and Health across Lives and Cohorts: A Study of Cumulative
      (Dis)advantage and Its Rising Importance in Germany.
AB  - Research from the United States has supported two hypotheses. First, educational
      gaps in health widen with age-the cumulative (dis)advantage hypothesis. Second,
      this relationship has intensified across cohorts-the rising importance
      hypothesis. In this article, we used 23 waves of panel data (Socio-Economic Panel
      Study, 1992-2014) to examine both hypotheses in the German context. We considered
      individual and contextual influences on the association between education and
      health, and we assessed gender differences in health trajectories over the life
      course (ages 23 to 84) and across cohorts (born between 1930 and 1969). For
      women, we found no support for either hypothesis, as educational gaps in self
      rated health remained stable with age and across cohorts. Among men, we found
      support for both hypotheses, as educational gaps in self-rated health widened
      with age and increasingly in newer cohorts.

PMID- 29337608
TI  - Author's Perspectives on Their Highly Cited Papers Published in Foodborne
      Pathogens and Disease.

PMID- 29337607
TI  - Foodborne Disease Outbreaks in the United States: A Historical Overview.
AB  - Understanding the epidemiology of foodborne disease outbreaks (FBDOs) is
      important for informing investigation, control, and prevention methods. We
      examined annual summary FBDO data in the United States from 1938 to 2015, to help
      understand the epidemiology of outbreaks over time. Due to changes in reporting
      procedures, before 1998, the mean number of annual outbreaks was 378, and after
      that, it was 1062. A mean of 42% had a known etiology during 1961-1998; since
      then the etiology has been identified in ~65%, with a marked increase in the
      number of norovirus outbreaks. From 1967 to 1997, a mean of 41% of FBDOs occurred
      in restaurant settings, increasing to 60% in 1998-2015. Concurrently, the
      proportion of outbreaks occurring at a home decreased from 25% to 8%. The mean
      size of outbreaks has decreased over time, and the number of multistate outbreaks
      has increased. Many social, economic, environmental, technological, and
      regulatory changes have dramatically affected the epidemiology of foodborne
      disease over time.

PMID- 29337609
TI  - Persistent Goose Hemorrhagic Polyomavirus Infection on a Belgian Goose Farm.
AB  - Goose hemorrhagic polyomavirus (GHPV) is the causative agent of hemorrhagic
      nephritis enteritis of geese (HNEG), one of the major diseases of domestic geese
      in Europe. This case report describes a persistent outbreak of a GHPV infection
      on a Belgian goose farm. Clinical symptoms, necropsy lesions, and histopathologic
      lesions observed were compatible with previous reports of HNEG outbreaks. PCR
      analysis confirmed the diagnosis of GHPV. To our knowledge, this is the first
      report of an outbreak of a GHPV infection on a Belgian goose farm. This is
      evidence that GHPV is not only present in countries known for extensive waterfowl
      production, but disease outbreaks also occur in countries with less extensive
      goose production.

PMID- 29337611
TI  - Interactions Between Parasites and the Bacterial Microbiota of Chickens.
AB  - Except for the important role coccidia have as predisposing factors of necrotic
      enteritis, the role parasites play in the dynamics of a healthy microbiota of
      chickens is not well explored. This review describes the interactions of relevant
      intestinal parasites of chickens with bacteria. Infection with Eimeria spp. favor
      the growth of Clostridium perfringens and suppress the growth of many other
      bacteria by increasing viscosity and passage time of the ingesta, and by causing
      lesions to the intestinal mucosa that improve the availability of nutrients for
      C. perfringens. Conversely, there are indications that bacteria influence the
      course of disease after infections with Eimeria spp. Not much is known about
      intestinal cryptosporidiosis in chickens, but results in mice show that the
      intestinal microbiota induces some resistance against infection with
      Cryptosporidium parvum and that the innate immune response triggered by
      infections with cryptosporidia might have an effect on other intestinal microbes.
      Histomonas meleagridis depend on bacteria in vitro, and in vivo it will cause
      lesions in chickens only in the presence of bacteria. Blastocystis spp. are very
      common in chickens, but there is no information about interactions with bacteria.
      In humans, there is evidence of the correlation of the detection of Blastocystis
      and changes in the intestinal microbiota. There are indications of interactions
      between Ascaridia galli and various bacteria in chickens and Ascaridia spp. of
      mammals are known to produce various types of antimicrobial molecules. However,
      often the underlying mechanisms of these interactions between parasites and
      bacteria remain unknown and only correlations but not causation can be
      established.

PMID- 29337612
TI  - Impact of Controlling Bacteria in Feed on Broiler Performance During a
      Clostridial Challenge.
AB  - Three studies were conducted using Clostridium perfringens as an intestinal
      challenge to produce necrotic enteritis (NE). The studies consisted of two
      battery screening studies and one production study in floor pens. The purpose of
      the trials was to determine if reducing the level of microorganisms in feed
      consumed by broilers reduced the impact of a nonfeed-based Clostridial challenge.
      In all studies, C. perfringens challenged broilers consuming feed containing
      lower levels of microorganisms compared to control feed exhibited significantly (
      P < 0.05) better feed conversion (feed conversion was improved by 14% in battery
      trials and by 4.2% in the pen trial) than did C. perfringens-challenged broilers
      consuming control feed. In battery trials, body weight gain and NE-associated
      mortality were also significantly improved in C. perfringens-challenged broilers
      consuming feed containing lower levels of microorganisms (16.5% improvement in
      body weight gain and 72.5% reduction in NE-associated mortality). In the pen
      trial, body weight gain and NE-associated mortality appeared unaffected by feed
      microbial quality. No effect was observed on lesion scores. The present data
      indicate that reducing the level of microorganisms in feed can ameliorate some of
      the performance losses associated with a Clostridia challenge.

PMID- 29337613
TI  - Molecular Detection of Avian Influenza Virus from Sediment Samples in Waterfowl
      Habitats on the Delmarva Peninsula, United States.
AB  - Avian influenza viruses (AIV) affect many species of birds including waterfowl
      and may persist in sediment in aquatic habitats. Sediment samples were collected
      from two areas representative of prime migration and overwintering waterfowl
      habitat in Dorchester County, Maryland in the fall and winter of 2013-2014.
      Samples were screened for the presence of AIV via reverse transcriptase
      quantitative PCR targeting the matrix gene. Although 13.6% of sediment samples
      were positive for the AIV matrix gene across all collection dates and locations,
      differences in detection were noted with location and collection season.
      Percentage of AIV-positive sediment samples recovered corresponded to trends in
      waterfowl abundance at collection sites both temporally and spatially. These
      findings provide further support for the assertion that the presence of AIV in
      the aquatic environment is likely affected by the total number, site-specific
      density, and array of waterfowl species.

PMID- 29337614
TI  - Response of House Finches Recovered from Mycoplasma gallisepticum to Reinfection
      with a Heterologous Strain.
AB  - After recovery, house finches ( Haemorhous mexicanus) reinfected with the same
      Mycoplasma gallisepticum strain remain partially resistant to reinfection for at
      least 14 mo in that they recover from reinfection much more rapidly than do
      Mycoplasma gallisepticum-naive birds. To test the response of birds to
      reinfection with a heterologous strain we performed two experiments. In a first
      experiment we exposed birds to one of three strains that differed in virulence.
      After they had recovered all were reinfected with the most virulent-strain
      available at the time of the experiment. In a second experiment we infected and
      later reinfected house finches with one of two Mycoplasma gallisepticum strains
      whereby we switched the order of the strain used. In both experiments, disease in
      birds reinfected with a more-virulent strain caused more-severe disease. Our data
      suggest that the observed increase in Mycoplasma gallisepticum virulence, once
      the disease has become endemic in free-ranging house finches is-in part-driven by
      increased resistance of recovered birds to strains of equal or lower virulence.

PMID- 29337615
TI  - Efficacy of Massachusetts and 793B Vaccines Against Infectious Bronchitis
      Moroccan-Italy 02 Virus in Specific-Pathogen-Free Chickens and Commercial
      Broilers.
AB  - The ability of commercial vaccines H120 and 4/91 to protect against Moroccan
      Italy 02 infectious bronchitis virus (Mor-It02) was investigated in specific
      pathogen-free (SPF) chickens and commercial broiler chickens. Commercial broiler
      chicks (Experiment 1) were vaccinated at the hatchery with H120 vaccine at Day 1,
      and challenged at Day 21 with 104 50% egg-infective dose (EID50) of Mor-It02. All
      chicks were observed daily for clinical signs attributable to Mor-It02 infection
      during the 10 days postchallenge (pc). At 5 and 10 days pc, chicks were humanely
      sacrificed for necropsy examination, and tissues were collected for
      histopathology evaluation. To better understand the findings on commercial
      broilers, day-old SPF chicks were divided into five groups in a second
      experiment: Group Mass/4-91, vaccinated with H120 and 4/91 respectively at Days 1
      and 15 of age; Group Mass/Mass, vaccinated by H120 at Days 1 and 15; Group Mass,
      vaccinated with H120 at Day 1; Group NV, kept unvaccinated; and Group NC, kept as
      a negative control (unchallenged). At Day 24 of age, Groups Mass/4-91, Mass/Mass,
      Mass, and NV were challenged with 104 EID50 of Mor-It02. In both experiments,
      blood samples were collected at different periods for serologic analyses.
      Oropharyngeal swabs were collected for virus detection by reverse-transcription
      PCR. In Experiments 1 and 2, respiratory signs started as early as 24 hr pc and
      maximum severity was observed on Days 3 and 4 pc. The viral shedding rate was
      significantly lower in Group Mass/4-91 compared to other challenged groups.
      Serologic analysis in both experiments showed that the sera of challenged group
      exhibited significantly higher antibody titers than sera collected before
      challenge. Histopathologic investigations in SPF birds showed deciliation and
      hyperplasia in Group NV and less-pronounced lesions in Groups Mass/Mass and Mass.
      In commercial broilers vaccinated with H120 alone, hyperplasia and deciliation
      were observed in 90% of the tracheas. These experiments illustrated that Mor-It02
      is pathogenic for chickens and a combination of live H120 and 4/91 vaccines given
      respectively at Day 1 and Day 15 of age confer a good protection against Mor
      It02.

PMID- 29337616
TI  - Chronologic Analysis of Gross and Histologic Lesions Induced by Field Strains of
      FAdV-1, FAdV-8b, and FAdV-11 in Six-Week-Old Chickens.
AB  - Inclusion body hepatitis (IBH) is a disease affecting broiler chicken flocks
      worldwide. Several serotypes of fowl adenovirus (FAdV) have been implicated in
      disease outbreaks, with and without immunosuppression as a predisposing factor.
      IBH usually occurs in flocks up to 30 days of age; it is seldom seen in older
      birds. The objective of this study was to determine whether the pathogenicity for
      older birds of three FAdV field strains, belonging to serotypes 1, 8b, and 11, in
      the absence of immunosuppressive factors, was akin to that for younger birds, and
      to establish an effective and economical disease model for assessing cross
      protection between serotypes. To achieve this objective, the gross pathology,
      histopathology, and dissemination of virus were examined at multiple time points
      after inoculation of 6-wk-old, specific-pathogen-free chickens via
      intraperitoneal injection. Both FAdV-8b and FAdV-11 generated lesions typical of
      those associated with outbreaks of IBH, and they were shown to be primary
      pathogens. The presence and severity of hepatic lesions were used to define two
      disease stages: degeneration (1-5 days postinoculation) and convalescence (6-14
      days postinoculation). During the degenerative stage, FAdV-8b was detected in the
      liver, kidney, and gizzard of most birds, whereas FAdV-11 was predominantly
      detected in the liver, and both viruses persisted in the gizzard into
      convalescence. The pathogenesis of two IBH-associated FAdV strains in 6-wk-old
      chickens confirms their high level of virulence and also provides an effective
      experimental model for investigation of cross-protection between FAdVs. It also
      demonstrates persistence of the virus in the gizzard long after infection,
      supporting the notion that it is a site of viral shedding.

PMID- 29337617
TI  - Intrapulmonary Delivery of CpG-ODN Microdroplets Provides Protection Against
      Escherichia coli Septicemia in Neonatal Broiler Chickens.
AB  - Synthetic oligodeoxynucleotides (ODN) containing unmethylated cytosine
      phosphodiester guanine (CpG) motifs (CpG-ODN) are effective immunostimulatory
      agents against a variety of viral, bacterial, and protozoan diseases in different
      animals including poultry. We have recently demonstrated that in ovo injection of
      CpG-ODN confers protection in neonatal chickens against bacterial septicemias.
      The objective of this study was to investigate the effectiveness of needle-free
      intrapulmonary (IPL) delivery of CpG-ODN microdroplets against Escherichia coli
      infection in neonatal chicks. In the present study, we used 880 chicks in total
      keeping 40 chicks per group. Chicks were delivered CpG-ODN or saline by IPL at
      the day 1 of hatch. Three days later, chicks were challenged with two doses (1 *
      104 CFU, n = 20 or 1 * 105 CFU, n = 20) of E. coli. Chicks treated with CpG-ODN
      by the IPL route had significantly lower clinical signs and bacterial load
      compared to the group treated with saline ( P < 0.05). CpG-ODN-treated groups
      were significantly protected against E. coli septicemia. We observed dose- and
      exposure time-dependent immunoprotective effects of IPL CpG-ODN in chicks. We
      found that IPL delivery of CpG-ODN can induce protective immunity as early as 6
      hr that remains effective at least until day 5 post-treatment. Moreover, there
      were no adverse effects of IPL delivery of CpG-ODN on growth or mortality up to
      42 days of age. Based on these findings, it can be suggested that CpG-ODN
      delivery by IPL route can be a promising alternative to antibiotics for inducing
      protective immunity in chicks during the critical first week of neonatal life.

PMID- 29337618
TI  - Vegetative Valvular Endocarditis and Hepatitis Associated with Helcococcus ovis
      in a 7-year-old White Leghorn Rooster.
AB  - Helcococcus ovis is a slow-growing, pyridoxal-dependent, Gram-positive coccus
      belonging to the Peptostreptococcaceae family. Bacteria belonging to the genus
      Helcococcus are considered normal inhabitants of keratinized epithelium in
      humans; however, several reports support their role as pathogens in humans and
      several animal species. This case report describes the identification of H. ovis
      in a white leghorn rooster with valvular vegetative endocarditis and hepatitis.
      In February 2017 one dead, 7-yr-old, white leghorn rooster was submitted to the
      California Animal Health and Food Safety Turlock laboratory for diagnostic
      testing. Postmortem and microscopic examination revealed vegetative endocarditis
      and aortic thrombosis associated with large numbers of Gram-positive cocci.
      Myocarditis and extensive necrotic hepatitis were also noticed. Helcococcus ovis
      was isolated in large numbers from the aortic endothelium and confirmed by matrix
      assisted laser desorption ionization time-of-flight mass spectrometry. Bacterial
      colonies become evident 48 hr postincubation and exhibited a satellite growth
      around Escherichia coli on blood agar plates. A similar relationship has been
      described between Helcococcus spp. and Staphylococcus aureus. The primary site of
      infection in this chicken was not determined. To our understanding this is the
      first report of H. ovis infection in an avian species. The fastidious nature and
      nutritional requirements of Helcococcus spp. must be considered in order to allow
      proper identification and avoid misdiagnosis. Further studies are needed to
      define pathogenesis, virulence factors, and predisposing conditions associated
      with this microorganism.

PMID- 29337620
TI  - 2017 AAAP Awards.

PMID- 29337619
TI  - The Role of Necroptosis, Apoptosis, and Inflammation in Fowl Cholera-Associated
      Liver Injury in a Chicken Model.
AB  - Fowl cholera resulting from infection with Pasteurella multocida causes huge
      economic losses in the poultry industry. Necrotic hepatitis is reported to be a
      significant lesion associated with fowl cholera in chickens. Clarifying the
      underlying molecular mechanism of hepatic injury caused by P. multocida infection
      is needed to develop new strategies to control fowl cholera. Pasteurella
      multocida Q (the standard reference strain) and P. multocida 1G1 (a clinical
      strain) were used to infect healthy laying hens. Clinical signs were observed and
      gross lesions in livers were observed postmortem. Histologic lesions and the
      localization and expression of protein molecules associated with necroptosis,
      apoptosis, and inflammation in hepatic tissues were examined by hematoxylin and
      eosin staining and immunohistochemistry. Western blot analysis was used to
      determine the expression of liver injury-related genes. Necroptotic molecules
      such as RIPK1 (receptor interaction protein kinases 1), RIPK3 (receptor
      interaction protein kinases 3), and MLKL (mixed lineage kinase domain-like
      protein) were observed by immunostaining primarily in the cytoplasm of
      hepatocytes within or around necrotic foci, and inflammatory mediators HMGB1
      (high-mobility group box 1) and IL-6 (interleukin-6) were found in the cytoplasm
      of heterophils, monocytes/macrophages, and hepatic sinusoids. In addition, MMP9
      (matrix metalloproteinase 9) and TIMP1 (tissue inhibitor of metalloproteinase 1)
      were observed in hepatic parenchymal cells, inflammatory cells, and interstitial
      spaces, whereas the apoptotic effector molecule caspase-3 (cysteine-containing
      aspartic proteolytic enzymes 3) was mainly found in hepatocytes. The expression
      of RIPK1, RIPK3, and MLKL was significantly higher in the infected chickens than
      in the controls. HMGB1 and IL-6 protein levels were also increased in infected
      chickens relative to those in controls. Both MMP9 and TIMP1 were highly expressed
      in infected chickens. In addition, caspase-3 protein levels were significantly
      elevated in infected chickens. Necroptosis, apoptosis, and inflammation played a
      significant role in hepatic injury caused by P. multocida.

PMID- 29337622
TI  - Isolation of Avipoxvirus from Tongue of Canaries ( Serinus canaria) Show Severe
      Localized Proliferative Glossitis.
AB  - Poxvirus was the causative agent of two unusual outbreaks of proliferative
      glossitis in canary ( Serinus canaria forma domestica) breeders in the Northern
      Italy. A total of 45, 7-9-mo-old canaries were submitted in fair postmortem
      conditions to the Istituto Zooprofilattico Sperimentale delle Venezie at the
      beginning of November 2005 for diagnostic investigation. Birds belonged to two
      unrelated and geographically distant aviaries in northern Italy, herein
      identified as Aviary A and Aviary B. The two breeder flocks had both attended the
      same bird exposition held at the beginning of October and started experiencing an
      onset of high mortality 3 wk after the show. Twelve red factor-melanin canaries
      from Aviary A (Mantua) and 33 dominant white and recessive white canaries from
      Aviary B (Vicenza) were submitted for laboratory investigations. Clinical signs
      were unspecific and consisted of depression, ruffling of the feathers, epistaxis,
      and anorexia due to decreased feed and water intake. Postmortem findings revealed
      a severe increase in volume, thickening, and hardening of the tongue, which had
      turned pinkish to dark brown. No apparent gross lesions were noticed in
      integumentary, respiratory, and digestive systems or other internal organs.
      Histopathologic evaluation of the tongue revealed severe proliferation of the
      stratified squamous epithelium containing numerous large eosinophilic
      intracytoplasmic inclusion bodies (Bollinger bodies) displacing the nuclei of the
      cells peripherally. Severe ulceration of the surface epithelium,
      fibrinoheterophilic plaque formation, and moderate basal lymphoplasmacytic
      infiltrations were also associated with the proliferative lesion. Poxvirus was
      successfully isolated from the lesions in tissue cultures but not in specific
      pathogen-free chicken embryonated eggs. Typical large, brick-shaped viral
      particles of 300-450 nm were also observed in affected tongues by transmission
      electron microscopy. This is the first report of multiple outbreaks of "poxvirus
      glossitis" in canaries.

PMID- 29337623
TI  - Fibrillar Collagen Organization Associated with Broiler Wooden Breast Fibrotic
      Myopathy.
AB  - Wooden breast (WB) is a fibrotic myopathy affecting the pectoralis major (p.
      major) muscle in fast-growing commercial broiler lines. Birds with WB are
      phenotypically detected by the palpation of a hard p. major muscle. A primary
      feature of WB is the fibrosis of muscle with the replacement of muscle fibers
      with extracellular matrix proteins, such as collagen. The ability of a tissue to
      be pliable and stretch is associated with the organization of collagen fibrils in
      the connective tissue areas surrounding muscle fiber bundles (perimysium) and
      around individual muscle fibers (endomysium). The objective of this study was to
      compare the structure and organization of fibrillar collagen by using
      transmission electron microscopy in two fast-growing broiler lines (Lines A and
      B) with incidence of WB to a slower growing broiler Line C with no phenotypically
      detectable WB. In Line A, the collagen fibrils were tightly packed in a parallel
      organization, whereas in Line B, the collagen fibrils were randomly aligned.
      Tightly packed collagen fibrils arranged in parallel are associated with
      nonpliable collagen that is highly cross-linked. This will lead to a
      phenotypically hard p. major muscle. In Line C, the fibrillar collagen was sparse
      in its distribution. Furthermore, the average collagen fibril diameter and
      banding D-period length were altered in Line A p. major muscles affected with WB.
      Taken together, these data are suggestive of different fibrotic myopathies beyond
      just what is classified as WB in fast-growing broiler lines.

PMID- 29337625
TI  - Molecular Characterization of QX-Like and Variant Infectious Bronchitis Virus
      Strains in Malaysia Based on Partial Genomic Sequences Comprising the S-3a/3b-E-M
      Intergenic Region-5a/5b-N Gene Order.
AB  - Infectious bronchitis virus (IBV) is one of the major poultry pathogens of global
      importance. However, the prevalence of IBV strains in Malaysia is poorly
      characterized. The partial genomic sequences (6.8 kb) comprising the S-3a/3b-E-M
      intergenic region-5a/5b-N gene order of 11 Malaysian IBVs isolated in 2014 and
      2015 were sequenced using next-generation sequencing technology. Phylogenetic and
      pairwise sequence comparison analysis showed that the isolated IBVs are divided
      into two groups. Group 1 (IBS124/2015, IBS125/2015, IBS126/2015, IBS130/2015,
      IBS131/2015, IBS138/2015, and IBS142/2015) shared 90%-95% nucleotide and deduced
      amino acid similarities to the QX-like strain. Among these isolates, IBS142/2015
      is the first IBV detected in Sarawak state located in East Malaysia (Borneo
      Island). Meanwhile, IBV isolates in Group 2 (IBS037A/2015, IBS037B/2015,
      IBS051/2015, and IBS180/2015) were 91.62% and 89.09% identical to Malaysian
      variant strain MH5365/95 (EU086600) at nucleotide and amino acid levels,
      respectively. In addition, all studied IBVs were distinctly separate from
      Massachusetts (70%-72% amino acid similarity) and European strains including
      793/B, Italy-02, and D274 (68%-73% amino acid similarity). Viruses in Group 1
      have the insertion of three amino acids at positions 23, 121, and 122 of the S1
      protein and recombinant events detected at nucleotide position 4354-5864, with
      major parental sequence derived from QX-like (CK-CH-IBYZ-2011) and a minor
      parental sequence derived from Massachusetts vaccine strain (H120). This study
      demonstrated coexistence of the IBV Malaysian variant strain along with the QX
      like strain in Malaysia.

PMID- 29337626
TI  - Comparative Analysis of Pasteurella multocida Isolates from Acute and Chronic
      Fowl Cholera Cases in Hungary During the Period 2005 Through 2010.
AB  - Fowl cholera (FC) is a highly contagious and economically important disease of
      poultry worldwide. This study was performed on 218 Pasteurella multocida isolates
      collected from separated breeding farms or backyards with acute and chronic FC
      cases in multiple localities across Hungary during the period 2005-2010. All
      isolates were characterized by a broad range of biochemical, serological, and
      molecular methods, as well as their antibiotic susceptibility to aminoglycosides
      (A), macrolides (M), penicillins (P), quinolones (Q), cephalosporins,
      sulphonamides (S), and tetracyclines (T) was determined. Fifty-two percent of all
      isolates belonged to a well-defined type that was highly virulent, caused acute
      FC, and had the same character: fermented L-arabinose, possessed capsule type A,
      identified as Heddleston serotype 1, and possessed allele type A of the ptfA
      fimbrial gene. This type was widely distributed among poultry in Hungary,
      especially in waterfowl flocks. Isolates collected from the chronic FC cases were
      more diverse: none of them fermented L-arabinose; they possessed capsule type A
      (76%), F (9%), or was non-typeable (15%) with different Heddleston serotypes,
      mainly 1, 3, 4, and 5, or 7 and 16; in addition, possessed allele type B of ptfA
      fimbrial gene. Only 26 isolates presented characters similar to any of the
      chronic FC cases but caused severe disease. The antibiotic susceptibility assay
      presented that 80% of all isolates were resistant to 1-5 of the studied
      antimicrobial agents. During the survey, after two years, there was a dramatic
      decline both in the number of the multi-drug resistance phenotypes and the
      prevalence of the highly virulent type of the isolates. In the next four years,
      multiresistant isolates were almost completely removed, whereas the number of
      isolates resistant to 1 or 2 drugs was constant. Reduced frequency of antibiotic
      multiresistant, mostly L-arabinose-fermenting isolates, has been observed since
      2007. This reduction may be a consequence of the elimination of multiple
      waterfowl flocks in Hungary during avian influenza outbreaks, which possibly
      created a break in the "transmission chain" of pathogenic P. multocida isolates.

PMID- 29337627
TI  - Increased Incidence of Enterococcal Infection in Nonviable Broiler Chicken
      Embryos in Western Canadian Hatcheries as Detected by Matrix-Assisted Laser
      Desorption/Ionization-Time-of-Flight Mass Spectrometry.
AB  - The emergence of enterococcal infections in neonatal broiler chickens in the
      poultry industry has become common in many countries, including Canada. The
      objective of this study was to examine the bacterial infections in nonviable
      broiler chicken embryos in three western Canadian poultry hatcheries using matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF
      MS). The pattern of embryo mortality that occurred during incubation and the
      breakout analysis results were similar in all three hatcheries. The majority of
      embryo mortality occurred during the late stage of incubation (35.08%), followed
      by the early stage of incubation (15.35%). The breakout analysis showed that
      65.82% of swabs had at least one type of bacterial growth while 34.17% of swabs
      were negative for bacterial isolation. Of those 65.82% swabs with bacterial
      growth, 34.3% of swabs yielded a mixed bacterial population while 31.52% yielded
      one type of bacterial growth. The frequency of bacterial isolation from hatch
      debris (60%-75%) increased with the age of broiler breeders. MALDI-TOF MS was
      able to provide genus-level identification of 83.13% of isolates among all
      bacterial types isolated. MALDI-TOF MS identified Enterococcus and Escherichia
      coli isolates with 97.18% and 100% accuracy at species level, respectively,
      whereas Staphylococcus species were identified with 62.59% accuracy. The
      congruence between MALDI-TOF MS identification and 16S rRNA or cpn60 universal
      gene target sequencing was 100% or 90%, respectively. Of all bacteria isolated,
      Enterococcus species (29.71%) were the most prevalent, followed by E. coli
      (19.46%). About 56% of E. coli-infected samples were coinfected with Enterococcus
      species. Among all Enterococcus species isolated, Enterococcus faecalis (79.58%)
      was the most prevalent, followed by Enterococcus faecium (8.1%). Overall, our
      study showed that Enterococcus-associated embryo mortality was predominant in all
      three hatcheries investigated and suggests that MALDI-TOF MS technology can be
      applied to identify bacteria such as Enterococcus species isolated from poultry.

PMID- 29337629
TI  - Biotech crop planting resumes high adoption in 2016.
AB  - The global area of biotech crops in 2016 increased from 179.7 million hectares to
      185.1 million hectares, a 3% increase equivalent to 5.4 million hectares. Some 26
      countries planted biotech crops, 19 of which were developing countries and seven
      were industrial. Information and data collected from various credible sources
      showed variations from the previous year. Fluctuations in biotech crop area (both
      increases and decreases) are influenced by factors including, among others,
      acceptance and commercialization of new products, demand for meat and livestock
      feeds, weather conditions, global market price, disease/pest pressure, and
      government's enabling policies. Countries which have increased biotech crop area
      in decreasing order in 2016 were Brazil, United States of America, Canada, South
      Africa, Australia, Bolivia, Philippines, Spain, Vietnam, Bangladesh, Colombia,
      Honduras, Chile, Sudan, Slovakia, and Costa Rica. Countries with decreased
      biotech area in decreasing order were China, India, Argentina, Paraguay, Uruguay,
      Mexico, Portugal, and Czech Republic, in decreasing incremental decrease in
      biotech area. Pakistan and Myanmar were the only countries with no change in
      biotech crop (cotton) planted. Information detailed in the paper including future
      crops and traits in each country could guide stakeholders in informed crafting of
      strategies and policies for increased adoption of biotech crops in the country.

PMID- 29337630
TI  - Ethnic differences in craniofacial and upper spine morphology in children with
      skeletal Class II malocclusion.
AB  - OBJECTIVES: To analyze differences in upper cervical spine and craniofacial
      morphology, including posterior cranial fossa and growth prediction signs,
      between Danish and South Korean pre-orthodontic skeletal Class II children and to
      analyze associations between upper cervical spine morphology and craniofacial
      characteristics. MATERIALS AND METHODS: One hundred forty-six skeletal Class II
      children-93 Danes (54 boys and 39 girls, mean age 12.2 years) and 53 Koreans (27
      boys and 26 girls, mean age 10.8 years)-were included. Upper spine morphology,
      Atlas dimensions, and craniofacial morphology, including posterior cranial fossa
      and growth prediction signs, were assessed on lateral cephalograms. Differences
      and associations were analyzed by multiple linear and logistic regression
      analyses adjusted for age and gender. RESULTS: Significant differences between
      the ethnic groups were found in the sagittal and vertical craniofacial dimensions
      ( P < .001), mandibular shape ( P < .01), dental relationship ( P < .01),
      posterior cranial fossa ( P < .05), and growth prediction signs ( P < .001). No
      significant differences were found in upper spine morphology and Atlas dimensions
      between the groups. Upper spine morphology/dimensions were significantly
      associated with the cranial base angle ( P < .01), sagittal craniofacial
      dimensions ( P < .001), posterior cranial fossa ( P < .001), and growth
      prediction signs ( P < .05). CONCLUSIONS: Upper spine morphology/dimensions may
      be valuable as predictive factors in treatment planning for growing Class II
      children.

PMID- 29337631
TI  - The cervical vertebral maturation method: A user's guide.
AB  - The cervical vertebral maturation (CVM) method is used to determine the
      craniofacial skeletal maturational stage of an individual at a specific time
      point during the growth process. This diagnostic approach uses data derived from
      the second (C2), third (C3), and fourth (C4) cervical vertebrae, as visualized in
      a two-dimensional lateral cephalogram. Six maturational stages of those three
      cervical vertebrae can be determined, based on the morphology of their bodies.
      The first step is to evaluate the inferior border of these vertebral bodies,
      determining whether they are flat or concave (ie, presence of a visible notch).
      The second step in the analysis is to evaluate the shape of C3 and C4. These
      vertebral bodies change in shape in a typical sequence, progressing from
      trapezoidal to rectangular horizontal, to square, and to rectangular vertical.
      Typically, cervical stages (CSs) 1 and CS 2 are considered prepubertal, CS 3 and
      CS 4 circumpubertal, and CS 5 and CS 6 postpubertal. Criticism has been rendered
      as to the reproducibility of the CVM method. Diminished reliability may be
      observed at least in part due to the lack of a definitive description of the
      staging procedure in the literature. Based on the now nearly 20 years of
      experience in staging cervical vertebrae, this article was prepared as a "user's
      guide" that describes the CVM stages in detail in attempt to help the reader use
      this approach in everyday clinical practice.

PMID- 29337632
TI  - The usefulness of cone-beam computed tomography gray values for alveolar bone
      linear measurements.
AB  - OBJECTIVES: To test a proof-of-concept that the accuracy and reliability of
      alveolar bone height measurements from orthodontic grade (large field-of-view
      [FOV], large voxel-size) cone-beam computed tomography (CBCT) images may be
      improved by using pixel gray values. MATERIALS AND METHODS: Twenty fresh cadaver
      pig heads underwent CBCT scans (17 * 23 cm FOV, 0.4-mm voxel size). Buccal
      alveolar bone heights of maxillary first molars were measured using the
      conventional vision-based (VB) and the proposed gray value-assisted (GVA)
      methods. The GVA methods entailed localization of landmarks through observation
      of gray value pattern changes across tissue boundaries followed by mathematical
      calculation of distances between landmark pixels. Interrater reliability and
      accuracy of CBCT measurements made by all methods were statistically analyzed by
      comparing with physical measurements (gold standards). RESULTS: The interrater
      reliability of CBCT measurements made by GVA methods was comparable to physical
      measurements but higher than those made by the VB method. The GVA (bend-down
      pattern) method yielded average measurements similar to physical measurements,
      while those obtained by the VB and the GVA (straight pattern) methods were
      significantly larger (repeated measures analysis of variance, P < .001). The GVA
      (bend-down pattern) method also produced significantly more measurements within
      one voxel size of physical measurements than did the VB and GVA (straight
      pattern) methods (Chi-square tests, P < .017). CONCLUSIONS: These data confirm a
      concept that local gray value change patterns may be used to improve the accuracy
      and reliability of alveolar bone height measurement from large FOV and large
      voxel-size CBCT images.

PMID- 29337633
TI  - Three-dimensional evaluation of maxillary dentoalveolar changes and airway space
      after distalization in adults.
AB  - OBJECTIVES: To evaluate the changes in position of the maxillary dentition and
      the airway space after distalization using a modified C-palatal plate (MCPP) in
      adult patients through CBCT images and to analyze the relationship between the
      amount of distalization and the changes in the airway space. MATERIALS AND
      METHODS: CBCT images of 33 adult Class II patients (22.2 +/- 4.0 years old; 27
      women and 6 men) treated by total maxillary arch distalization using the MCPP
      were evaluated before and after distalization. The patients were divided into
      nonextraction and extraction groups. The changes in the airway space as well as
      the changes in the positions of the maxillary dentition were evaluated. The
      distalization effects were calculated and assessed using paired t-tests. RESULTS:
      After distalization, the first molar showed significant distalization and
      intrusion ( P < .001) with no significant rotation of the crown and no
      significant buccal displacement of its root in the transverse dimension. There
      were no significant changes in the airway volume or the minimum cross-sectional
      area of the oropharynx. CONCLUSIONS: The application of the MCPP resulted in
      significant total arch distalization without a significant effect on the
      transverse dimensions or changes in the oropharynx airway space. The MCPP can be
      considered a viable treatment option for patients with Class II malocclusion.

PMID- 29337634
TI  - Risk factors associated with open gingival embrasures after orthodontic
      treatment.
AB  - OBJECTIVES: To investigate the incidence of and contributing factors to open
      gingival embrasures between the central incisors after orthodontic treatment.
      MATERIALS AND METHODS: One hundred posttreatment patients (29 men and 71 women;
      mean age, 24.7 years) were divided retrospectively into occurrence and
      nonoccurrence groups based on intraoral photographs. Based on the severity, the
      occurrence group was further divided into mild, moderate, and severe groups.
      Parameters from periapical radiographs, superimposed lateral cephalograms, and
      study models were compared between the occurrence and the nonoccurrence groups by
      using independent t-tests and were also analyzed on the basis of severity via
      analysis of variance. Logistic regression analysis was performed to identify the
      contributing factors to open gingival embrasures. RESULTS: The incidence of open
      gingival embrasures between the central incisors was 22% and 36% in the maxilla
      and the mandible, respectively. Lingual movement of the incisors, distance from
      the contact point to the alveolar crest after treatment, antero-posterior overlap
      of the two central incisors before treatment in the maxilla, and distance from
      the contact point to the alveolar crest after treatment in the mandible were
      significantly associated with the occurrence of open gingival embrasures ( P <
      .05). In the mandible, the amount of intrusion was significantly related to
      severity ( P < .05). CONCLUSIONS: The incidence of open gingival embrasures
      following orthodontic tooth movement is high. Therefore, attention should be paid
      to the contributing factors to prevent or reduce the occurrence of open gingival
      embrasures.

PMID- 29337635
TI  - Reply to M. Horiguchi et al.

PMID- 29337636
TI  - New-Onset Cardiovascular Morbidity in Older Adults With Stage I to III Colorectal
      Cancer.
AB  - Purpose We sought to determine the long-term risk of cardiovascular disease (CVD)
      stroke and myocardial infarction-and congestive heart failure (CHF) in older
      patients with colorectal cancer, as well as to understand the roles that
      preexisting comorbidities and cancer therapy play in increasing this risk.
      Patients and Methods We evaluated individuals from the SEER-Medicare database
      with incident stage I to III colorectal cancer at age older than 65 years between
      January 1, 2000, and December 31, 2011 (n = 72,408) and compared these patients
      with a matched cohort of Medicare patients without cancer (n = 72,408). Results
      Median age at diagnosis of colorectal cancer was 78 years (range, 66 years to 106
      years), and median follow-up was 8 years since diagnosis. The 10-year cumulative
      incidence of new-onset CVD and CHF were 57.4% and 54.5% compared with 22% and 18%
      for control, respectively ( P < .001). The interaction between hypertension and
      chemotherapy was significant ( P < .001) for CVD, and that between diabetes and
      chemotherapy was significant ( P < .001) for CHF. Within the first 2 years since
      diagnosis, exposure to capecitabine alone increased CHF hazard (hazard ratio
      [HR], 3.6; 95% CI, 12.76 to 4.38) compared with exposure to fluorouracil alone.
      Conversely, patients who were treated with fluorouracil alone had a higher CVD
      hazard at < 2 years and > 2 years since diagnosis compared with patients who
      received capecitabine alone (< 2 years HR, 0.63; 95% CI, 0.53 to 0.75; > 2 years
      HR, 0.72; 95% CI, 0.62 to 0.84). Conclusion Older patients with colorectal cancer
      are at increased risk of developing CVD and CHF. Diabetes and hypertension
      interact with chemotherapy to increase the risk of cardiovascular morbidity.
      Future studies should assess the potential for personalized therapeutic options
      for those with preexisting morbidities and for structured monitoring for patients
      with a history of exposure to chemotherapy regimens, as well as explore the
      management of preexisting comorbidities to address long-term cardiovascular
      morbidity.

PMID- 29337637
TI  - Tumor Mutation Burden: Leading Immunotherapy to the Era of Precision Medicine?

PMID- 29337638
TI  - Patients With Advanced Melanoma Who Discontinued Treatment With Nivolumab and
      Ipilimumab as a Result of Adverse Events Lived Significantly Longer Than Patients
      Who Continued Treatment.

PMID- 29337639
TI  - Reply to M. Horiguchi et al.

PMID- 29337641
TI  - Strain-Specific Symbiotic Genes: A New Level of Control in the Intracellular
      Accommodation of Rhizobia Within Legume Nodule Cells.
AB  - This is a short commentary on the article by Wang et al. published in MPMI Vol.
      31, No. 2, pages 240-248.

PMID- 29337640
TI  - Molecular Determinants of Response to Anti-Programmed Cell Death (PD)-1 and Anti
      Programmed Death-Ligand 1 (PD-L1) Blockade in Patients With Non-Small-Cell Lung
      Cancer Profiled With Targeted Next-Generation Sequencing.
AB  - Purpose Treatment of advanced non-small-cell lung cancer with immune checkpoint
      inhibitors (ICIs) is characterized by durable responses and improved survival in
      a subset of patients. Clinically available tools to optimize use of ICIs and
      understand the molecular determinants of response are needed. Targeted next
      generation sequencing (NGS) is increasingly routine, but its role in identifying
      predictors of response to ICIs is not known. Methods Detailed clinical annotation
      and response data were collected for patients with advanced non-small-cell lung
      cancer treated with anti-programmed death-1 or anti-programmed death-ligand 1
      [anti-programmed cell death (PD)-1] therapy and profiled by targeted NGS (MSK
      IMPACT; n = 240). Efficacy was assessed by Response Evaluation Criteria in Solid
      Tumors (RECIST) version 1.1, and durable clinical benefit (DCB) was defined as
      partial response/stable disease that lasted > 6 months. Tumor mutation burden
      (TMB), fraction of copy number-altered genome, and gene alterations were compared
      among patients with DCB and no durable benefit (NDB). Whole-exome sequencing
      (WES) was performed for 49 patients to compare quantification of TMB by targeted
      NGS versus WES. Results Estimates of TMB by targeted NGS correlated well with WES
      (rho = 0.86; P < .001). TMB was greater in patients with DCB than with NDB ( P =
      .006). DCB was more common, and progression-free survival was longer in patients
      at increasing thresholds above versus below the 50th percentile of TMB (38.6% v
      25.1%; P < .001; hazard ratio, 1.38; P = .024). The fraction of copy number
      altered genome was highest in those with NDB. Variants in EGFR and STK11
      associated with a lack of benefit. TMB and PD-L1 expression were independent
      variables, and a composite of TMB plus PD-L1 further enriched for benefit to
      ICIs. Conclusion Targeted NGS accurately estimates TMB and elevated TMB further
      improved likelihood of benefit to ICIs. TMB did not correlate with PD-L1
      expression; both variables had similar predictive capacity. The incorporation of
      both TMB and PD-L1 expression into multivariable predictive models should result
      in greater predictive power.

PMID- 29337642
TI  - Perineural Invasion in Parotid Gland Malignancies.
AB  - Objectives To investigate the clinical predictors and survival implications of
      perineural invasion (PNI) in parotid gland malignancies. Study Design Case series
      with chart review. Setting Tertiary care medical center. Subjects and Methods
      Patients with parotid gland malignancies treated surgically from 2000 to 2015
      were retrospectively identified in the Head and Neck Cancer Registry at a single
      institution. Data points were extracted from the medical record and original
      pathology reports. Results In total, 186 patients with parotid gland malignancies
      were identified with a mean follow-up of 5.2 years. Salivary duct carcinoma (45),
      mucoepidermoid carcinoma (44), and acinic cell carcinoma (26) were the most
      common histologic types. A total of 46.2% of tumors were found to have PNI. At
      the time of presentation, facial nerve paresis (odds ratio [OR], 64.7; P < .001)
      and facial pain (OR, 3.7; P = .002) but not facial paresthesia or anesthesia (OR,
      2.8, P = .085) were predictive of PNI. Malignancies with PNI were significantly
      more likely to be of advanced T and N classification, be high-risk pathologic
      types, and have positive margins and angiolymphatic invasion. PNI positivity was
      associated with worse overall (hazard ratio, 2.62; P = .001) and disease-free
      survival (4.18; P < .001) on univariate Cox regression analysis. However, when
      controlling for other negative prognosticators, age, and adjuvant therapy, PNI
      did not have a statistically significant effect on disease-free or overall
      survival. Conclusions PNI is strongly correlated with more aggressive parotid
      gland malignancies but is not an independent predictor of worse survival. Facial
      paresis and pain were predictive of PNI positivity, and facial paresis correlated
      with worse overall and disease-free survival.

PMID- 29337645
TI  - Conservative Approach for Treatment of Maxillary Lateral Incisor Agenesis With
      the Deciduous Tooth Retained: 18-Month Follow-Up.
AB  - This case describes a female patient with agenesis of the maxillary right lateral
      incisor, with her permanent canine in its position and the deciduous canine
      retained. Additionally, she presented with a maxillary left peg lateral incisor.
      To solve her functional and esthetic complaints, a multidisciplinary approach
      involving perio-restorative procedures was proposed. Periodontal surgeries were
      performed to align the gingival contour, and the restorative approach utilized
      ceramic veneers. At the 18-month clinical and radiographic follow-up, the
      treatment outcome was stable, with maintenance of the clinical results achieved
      and without any sign of deciduous tooth resorption.

PMID- 29337643
TI  - Models for predicting the evolution of influenza to inform vaccine strain
      selection.
AB  - Influenza vaccine composition is reviewed before every flu season because
      influenza viruses constantly evolve through antigenic changes. To inform vaccine
      updates, laboratories that contribute to the World Health Organization Global
      Influenza Surveillance and Response System monitor the antigenic phenotypes of
      circulating viruses all year round. Vaccine strains are selected in anticipation
      of the upcoming influenza season to allow adequate time for production. A
      mismatch between vaccine strains and predominant strains in the flu season can
      significantly reduce vaccine effectiveness. Models for predicting the evolution
      of influenza based on the relationship of genetic mutations and antigenic
      characteristics of circulating viruses may inform vaccine strain selection
      decisions. We review the literature on state-of-the-art tools and prediction
      methodologies utilized in modeling the evolution of influenza to inform vaccine
      strain selection. We then discuss areas that are open for improvement and need
      further research.

PMID- 29337644
TI  - Performance of Monolithic and Veneered Zirconia Crowns After Endodontic Treatment
      and Different Repair Strategies.
AB  - OBJECTIVES: To investigate failure loads of monolithic and veneered all-ceramic
      crowns after root canal treatment and to analyze marginal integrity of repair
      fillings. METHODS AND MATERIALS: Seventy-two human molars were restored with
      monolithic (Zr-All) or veneered (Zr-Ven) zirconia crowns. Molars were assigned to
      six groups (n=12 per group) depending on restoration material, access type (no
      access cavity [control] or endodontic treatment [test]), and type of filling (one
      step [1-st] or two-step [2-st]). For type of filling, molars were treated using a
      self-etch universal adhesive and cavities were either filled with layered
      composite (1-st) or filled until the crown material was reached, which was
      additionally conditioned and then filled (2-st). Scanning electron microscopic
      analysis of the restoration margins was performed before and after
      thermomechanical loading (TML), and the percentage of continuous margins was
      assessed. Crowns were then loaded to failure. RESULTS: Preparation of the access
      cavity required more time in monolithic (445 s) than in veneered crowns (342 s).
      Loads to failure were higher in control groups (Zr-All: 5814 N; Zr-Ven: 2133 N)
      and higher in monolithic test (2985 N) than in veneered test crowns (889 N). In
      monolithic crowns, 1-st had lower fracture loads than 2-st fillings (2149 N vs
      3821 N). Continuous margins of 66% to 71% were achieved, which deteriorated after
      TML by 39% to 40% in Zr-All, by 34% in Zr-Ven-1-st, and by 24% in Zr-Ven-2-st.
      CONCLUSIONS: Endodontic access and adhesive restorations resulted in reduced
      fracture load in monolithic and veneered zirconia crowns. Two-step fillings
      provided higher fracture loads in Zr-All and better marginal quality in Zr-Ven
      crowns.

PMID- 29337646
TI  - Stability of an aluminum salt-adjuvanted protein D-conjugated pneumococcal
      vaccine after exposure to subzero temperatures.
AB  - Accidental exposure of a vaccine containing an aluminum-salt adjuvant to
      temperatures below 0 degrees C in the cold chain can lead to freeze damage. Our
      study evaluated the potential for freeze damage in a licensed aluminum-salt
      containing protein-D-conjugated pneumococcal vaccine (PHiD-CV; Synflorix, GSK) in
      conditions that included static storage, single subzero-temperature excursions,
      and simulated air-freight transportation. Several parameters were assessed
      including freezing at subzero temperatures, aluminum-salt-particle size, antigen
      integrity and immunogenicity in the mouse. The suitability of the WHO's shake
      test for identifying freeze-damaged vaccines was also assessed. During subzero
      temperature excursions, the mean temperatures at which PHiD-CV froze (-16.7
      degrees C to -18.1 degrees C) appeared unaffected by the type of vaccine
      container (two-dose or four-dose vial, or single-dose syringe), vaccine batch,
      rotational agitation, or the rate of temperature decline (-0.5 to -10 degrees
      C/hour). At constant subzero temperature and in simulated air-freight
      transportation, the freezing of PHiD-CV appeared to be promoted by vibration. At 
      5 degrees C, no PHiD-CV sample froze in static storage (>1 month), whereas when
      subjected to vibration, a minority of samples froze (7/21, 33%) within 18 hours.
      At -8 degrees C with vibration, nearly all (5/6, 83%) samples froze. In these
      vibration regimes, the shake test identified most samples that froze (10/12, 93%)
      except two in the -5 degrees C regime. Nevertheless, PHiD-CV-antigen integrity
      appeared unaffected by freezing up to -20 degrees C or by vibration. And although
      aluminum-salt-particle size was increased only by freezing at -20 degrees C, PHiD
      CV immunogenicity appeared only marginally affected by freezing at -20 degrees C.
      Therefore, our study supports the use of the shake test to exclude freeze-damaged
      PHiD-CV in the field.

PMID- 29337647
TI  - Compositional Assessment of Human Tracheal Cartilage by Infrared Spectroscopy.
AB  - Objectives To assess the potential of infrared fiber-optic spectroscopy to
      evaluate the compositional properties of human tracheal cartilage. Study Design
      Laboratory-based study. Methods Twenty human cadaveric distal tracheas were
      harvested (age range 20-78 years; 6 females, 14 males) for compositional
      analysis. Histologic staining, Fourier transform infrared imaging spectroscopy
      data on collagen and proteoglycan (PG) content, and near-infrared (NIR) fiber
      optic probe spectroscopic data that reflect protein and water content were
      evaluated. NIR fiber-optic probe data were also obtained from the proximal
      trachea in 4 human cadavers (age range 51-65 years; 2 females, 2 males) in situ
      for comparison to distal trachea spectral data. Results In the distal trachea
      cohort, the spectroscopic-determined ratio of PG/amide I, indicative of the
      relative amount of PG, was significantly higher in the tissues from the younger
      group compared to the older group (0.37 +/- 0.08 vs 0.32 +/- 0.05, P = .05). A
      principal component analysis of the NIR spectral data enabled separation of
      spectra based on tracheal location, likely due to differences in both protein and
      water content. The NIR-determined water content based on the 5200-cm-1 peak was
      significantly higher in the distal trachea compared to the proximal trachea ( P <
      .001). Conclusions Establishment of normative compositional values and further
      elucidating differences between the segments of trachea will enable more directed
      research toward appropriate compositional end points in regenerative medicine for
      tracheal repair.

PMID- 29337648
TI  - Simultaneous amplification of exons 18 to 21 of the EGFR gene using 5' tailed
      primers and a two-stage protocol.
AB  - OBJECTIVE: Reduction of non-specific amplification and achievement of efficient
      amplification of multiple gene fragments under the same reaction condition is the
      basic goal of PCR diagnosis; however, this is often difficult. This study was
      conducted to establish a highly specific and effective amplification of the
      epidermal growth factor receptor (EGFR) gene's exons, 18-21, simultaneously.
      METHODS: The 5'-tailed primers were synthesized by adding 10 to 20 bp of a non
      specific sequence to the 5'-terminus of sequence-specific primers (tailless
      primers). The two-stage protocol consisted of 5-10 cycles of a conventional 3
      step cycling, which was then followed by 30-35 cycles of two-step cycling. The
      exons 18-21 of EGFR gene were amplified in 28 non-small cell lung cancer (NSCLC)
      patients using an optimized PCR that combined 5' tailed primers with a two-stage
      protocol. RESULTS: The 5' tailed primers exhibited a wider range of suitable
      annealing temperatures, similar range of primer concentration, similar
      sensitivity, specificity, and reproducibility, as well as a reduced, non-specific
      amplification compared with the corresponding tailless primers. The amplification
      of exons 18-21 of EGFR gene in NSCLC patients revealed that a combination of 5'
      tailed primers with two-stage protocol (optimized PCR) had a similar PCR success
      rate (P = 0.873) but had significantly reduced non-specific amplification (P
      <0.001) compared to conventional PCR. CONCLUSION: 5' tailed primers exhibited a
      wider range of suitable annealing temperatures and improved specificity compared
      with conventional PCR primers. An optimized PCR was established with 5' tailed
      primers and a two-stage protocol to amplify exons 18-21 of the EGFR gene in NSCLC
      patients.

PMID- 29337649
TI  - Neurocognitive Deficits Associated With ADHD in Athletes: A Systematic Review.
AB  - CONTEXT: Attention deficit hyperactivity disorder (ADHD) is a common childhood
      disorder and is frequently diagnosed in young adults. Emerging studies suggest a
      relationship between ADHD and concussion. OBJECTIVE: To determine whether
      athletes with ADHD are at increased risk for neurocognitive deficits related to
      concussion risk, symptom reporting, and recovery. DATA SOURCES: A comprehensive
      search of PubMed, CINAHL, PsychInfo, and Cochrane Library databases was
      performed. Studies conducted between 2006 and 2017 were reviewed, although only
      those between 2013 and 2017 met inclusion criteria. STUDY SELECTION: Studies that
      examined neurocognitive deficits in adolescent and young adult athletes aged 15
      to 19 years who had ADHD and reported using notable neuropsychological evaluation
      tools were included. STUDY DESIGN: Systematic review. LEVEL OF EVIDENCE: Level 2.
      RESULTS: A total of 17 studies met the inclusion criteria. The prevalence of ADHD
      in athletes varied between 4.2% and 8.1%. Overall, athletes with ADHD
      demonstrated lower scores on neurocognitive testing such as the ImPACT (Immediate
      Post-Concussion Assessment and Cognitive Test), increased risk for concussion,
      and increased symptom reporting. There was no evidence that treatment with
      stimulant medication changed these risks. CONCLUSION: ADHD is associated with
      increased neurocognitive deficits in athletes, although pathophysiology remains
      unclear. Evidence for stimulant treatment in athletes with ADHD continues to be
      sparse.

PMID- 29337650
TI  - The Association of External Transfer Status with Adverse Outcomes in
      Otolaryngology.
AB  - Objective To compare rates of morbidity and mortality in patients treated by
      otolaryngologists who undergo interhospital transfers vs those who do not and to
      quantify conditions requiring interhospital transfers in this population. Study
      Design Cohort study. Setting American College of Surgeons National Surgical
      Quality Improvement Program. Subjects and Methods We identified patients
      requiring surgery by otolaryngologists in the National Surgical Quality
      Improvement Program database from 2006 to 2013. We compared patients who were
      transferred from an outside institution to those admitted from home. Multivariate
      regression was used to adjust for patient characteristics, comorbidities, and
      case mix. The primary outcome was overall morbidity and mortality within 30 days
      of surgery. Results We identified 60,498 patients; 488 (0.8%) were transferred
      from another institution. Operations that were more common in the transferred
      group were incision and drainage (24.0% vs 1.2%), facial trauma repair (9.0% vs
      3.1%), and oropharyngeal hemorrhage control (3.9% vs 0.4%). External transfer
      patients had significantly longer hospital stays (44.1% vs 4.4% >7 days, P <
      .05). On unadjusted analysis, transferred patients had a significantly higher
      rate of morbidity and mortality (odds ratio [OR], 11.3; 95% confidence interval
      [CI], 9.4-13.5). On multivariate analysis, transferred patients had a
      significantly greater rate of morbidity and mortality (OR, 3.1; 95% CI, 2.4-4.0).
      Conclusion Transfer from another institution is associated with worse outcomes
      independent of case mix, demographics, and preoperative comorbidities in acute
      otolaryngology conditions requiring surgery. Practitioners should be aware of
      this when caring for transfer patients, and transfer status should be considered
      when measuring hospital quality.

PMID- 29337651
TI  - The effects of booster vaccination of hepatitis B vaccine on children 5-15 years
      after primary immunization: A 5-year follow-up study.
AB  - The aim of this study was to evaluate changes in hepatitis B surface antibody
      titers (anti-HBs) after booster vaccinations in children aged 5-15 y and to
      provide suitable immunization strategies. A total of 2208 children were initially
      enrolled in screening, and 559 children were finally included. The participants
      were divided into 2 groups according to their pre-booster anti-HBs levels: Group
      I, <10 mIU/ml and Group II, >=10 mIU/ml. Group I was administered 3 doses of
      booster hepatitis B vaccine (0-1-6 months, 10 MUg), and Group II was administered
      1 dose of booster hepatitis B vaccine (10 MUg). The antibody titer changes were
      examined at 4 time points: 1 month after dose 1 and dose 3, and 1 year and 5
      years after dose 3. The protective seroconversion rates at those points were
      95.65%, 99.67%, 97.59% and 91.05% (p < 0.001), respectively, in Group I, and
      100.00%, 99.87%, 99.66% and 98.21% (chi2 = 6.04, p = 0.11), respectively, in
      Group II. The GMT in subjects aged 5-9 y were higher than that in subjects aged
      10-15 y in both Group I and Group II at 1 month after dose 1, but no difference
      was observed at the other three time points. This study demonstrates that booster
      vaccination has a good medium-term effect. A booster dose for subjects with
      protective antibodies is not necessary but effective, and 3 doses of hepatitis B
      vaccination are recommended for those who have lost immunological memory.
      Receiving booster immunization at the age of 10-15 years may be more appropriate
      for individuals living in HBV high epidemic areas.

PMID- 29337652
TI  - Poorly neutralizing polyclonal antibody in vitro against coxsackievirus A16
      circulating strains can prevent a lethal challenge in vivo.
AB  - Neutralizing antibodies (NTAbs) is a major criterion for evaluation the
      immunogenicity of many vaccines, for example, poliovirus and EV71 vaccine. Here,
      we firstly discovered that polyclonal antibodies induced by inactivated CVA16
      vaccine and lived CVA16 virus have poor ability to neutralize circulating CVA16
      strains in vitro. However, the passive transfer of poorly neutralizing polyclonal
      antibodies can protect suckling mice from lethally challenged with circulating
      strains in vivo. In addition, the obvious dose response was found between the
      titer of antibodies and the survival rate. Interestingly, poorly neutralizing
      polyclonal antibodies against circulating CVA16 strains, have good ability to
      neutralize prototype strain G10 in vitro. Between G10 and circulating CVA16
      strains, there are total 47 variant sites in capsid, which are near the interface
      of VP1, VP2, and VP3, and close to 2-fold axis. Based on the structure of CVA16,
      the obvious structural changes were observed in residue 213 of VP1 GH loop,
      residue 139 of VP2 EF loop, and residues 59, 182 and 183 of VP3 GH loop. What we
      found may provide a new sight for the development of CVA16 vaccine.

PMID- 29337653
TI  - Safety and immunogenicity of a meningococcal B recombinant vaccine when
      administered with routine vaccines to healthy infants in Taiwan: A phase 3, open
      label, randomized study.
AB  - Neisseria meningitidis is associated with high mortality and morbidity in infants
      and children worldwide. This phase 3 study (NCT02173704) evaluated safety and
      immunogenicity of a 4-component serogroup B recombinant meningococcal vaccine
      (4CMenB) co-administered with routine vaccines in Taiwanese infants. In total,
      225 healthy infants were randomized (2 : 1 ) to receive 4CMenB and routine
      vaccines (4CMenB+Routine) or routine vaccines only (Routine group) at 2, 4, 6 and
      12 months of age. Routine vaccines were diphtheria-tetanus-acellular pertussis
      inactivated poliovirus-Haemophilus influenzae type b, 13-valent pneumococcal,
      hepatitis B, measles-mumps-rubella and varicella vaccines. Immune responses to
      4CMenB components (factor H binding protein [fHbp], Neisserial adhesin A [NadA],
      porin A [PorA] and Neisseria heparin-binding antigen [NHBA]) were evaluated at 1
      month post-primary and post-booster vaccination, using human serum bactericidal
      assay (hSBA). Reactogenicity and safety were also assessed. A sufficient immune
      response was demonstrated for fHbp, NadA and PorA, at 1 month post-primary and
      booster vaccination. In the 4CMenB+Routine group, hSBA titers >=5 were observed
      in all infants for fHbp and NadA, in 79% and 59% of infants for PorA and NHBA,
      respectively, at 1 month post-primary vaccination and in 92-99% of infants for
      all antigens, at 1 month post-booster vaccination. In the 4CMenB+Routine group,
      hSBA geometric mean titers for all antigens increased post-primary (8.41-963) and
      post-booster vaccination (17-2315) compared to baseline (1.01-1.36).
      Immunogenicity of 4CMenB was not impacted by co-administration with routine
      pediatric vaccines in infants. Reactogenicity was slightly higher in the
      4CMenB+Routine group compared with Routine group, but no safety concerns were
      identified.

PMID- 29337654
TI  - Oral Antihistamines Alone vs in Combination with Leukotriene Receptor Antagonists
      for Allergic Rhinitis: A Meta-analysis.
AB  - Objective To evaluate whether an adjuvant therapy of leukotriene receptor
      antagonists (LTRAs) based on oral H1-antihistamines (H1) can increase efficacy of
      allergic rhinitis (AR) treatment. Data Sources The search involved databases of
      PubMed, EMBASE, and Cochrane Central Register of Controlled Trials, from
      inception up to September 23, 2017. Randomized controlled trials (RCTs) that
      compared efficacy of LTRAs + H1 vs H1 alone were eligible. Review Methods Pooled
      comparative effects were measured using weighted mean difference (WMD) and 95%
      confidence interval (CI). Subgroup analysis comparing seasonal vs perennial AR
      was prespecified to explore the source of heterogeneity. The evidence quality of
      each outcome was assessed by the GRADE approach. Results A total of 8 RCTs were
      included (n = 1886), and all measured outcomes used scaled scores. Compared with
      H1 alone, H1 + LTRAs were superior to improve overall daytime (WMD, -0.11; 95%
      CI, -0.19 to -0.03, high quality) and composite (WMD, -0.12; 95% CI, -0.23 to 
      0.01; low quality) nasal symptoms. Specifically, H1 + LTRAs had better efficacy
      against composite nasal rhinorrhea, sneezing, and daytime itching but not
      congestion. The effects were more pronounced in patients with perennial AR
      compared to those with seasonal AR. There were no significant differences in
      nighttime nasal symptoms and eye symptoms between the 2 groups. Conclusion The
      current evidence suggests that LTRAs + H1 can increase the therapeutic efficacy
      against daytime and composite nasal symptoms, including rhinorrhea, sneezing, and
      itching; however, it does not affect nighttime nasal symptoms and eye symptoms.
      The patients with perennial AR may benefit more from the combination therapy.

PMID- 29337655
TI  - The Patient Who Continues to Smoke On-Treatment: An Ethical Dilemma.

PMID- 29337656
TI  - A review of methodology for the analysis of pyrethrin and pyrethroid residues in
      food of animal origin.
AB  - Pyrethrin and pyrethroid pesticides are commonly used in crop protection and
      animal health, to control pests. As a result, they can potentially transfer into
      food if good agricultural practice is not followed or even due to accidental
      contamination. The analysis of these compounds has been widely reported in crops
      and the environment. However, the analysis of pyrethrin and pyrethroids has not
      been reported frequently in foods of animal origin, particularly animal tissues.
      The focus of this review is to report on pyrethrin and pyrethroid analysis
      including key aspects such as chemistry, choice of target matrix, sample
      preparation, chemical analysis, legislation and method validation. This review
      shows that most methodologies for the analysis of these compounds are based on
      gas chromatography with the trend in recent years to move towards GC-MS or GC
      MS/MS based platforms. This review shows that these compounds can also be
      satisfactorily analysed by LC-MS/MS, which can be advantageous because of shorter
      chromatographic run times. A wide range of sample preparation procedures have
      been applied in analytical methods and more complex protocols are required for GC
      applications, whereas more crudely prepared extracts can be analysed by LC-MS/MS.
      This review demonstrates that pyrethrin and pyrethroid residues should be
      included as analytes in multi-class analytical methods for pesticides and
      veterinary drug residues in animal derived foods.

PMID- 29337657
TI  - The prevalence of deoxynivalenol and its derivatives in the spring wheat grain
      from different agricultural production systems in Lithuania.
AB  - Deoxynivalenol (DON) together with two acetylated derivatives, 3
      acetyldeoxynivalenol (3-ADON) and 15-acetyldeoxynivalenol (15-ADON) occurs in
      cereal grains and their products. Co-occurrence of DON and acetylated derivatives
      in cereal grain is detected worldwide. Until now, DON and its derivatives have
      been considered equally toxic by health authorities. In this study, we analysed
      103 samples of spring wheat grain, originating from the fields of different
      production systems in Lithuania, for the co-occurrence of type-B trichothecenes
      (DON, 3-ADON, 15-ADON). The samples were classified according to the production
      system-organic, sustainable and intensive. Mycotoxin levels in the spring wheat
      grain samples were determined by the HPLC method with UV detection. The type-B
      trichothecenes were found to be present at higher concentrations in the grain
      from the intensive production system. Eighty-one percent of the spring wheat
      grain samples from the intensive production system were co-contaminated with a
      combination of DON+3-ADON+15-ADON, 1% with DON+3-ADON. Additionally, DON+15-ADON
      and DON were found in 5% and 10% of the tested samples, respectively. Two percent
      of the samples were free from mycotoxins. In the grain samples from the
      sustainable production system, DON and a combination of DON+3-ADON showed a
      higher incidence - 47% and 23%, respectively. The samples with a combination of
      DON+3-ADON+15-ADON accounted for 18%. Completely different results were obtained
      from the analyses of organic grain samples. A large number of the organic spring
      wheat grain samples were contaminated with DON+3-ADON (55%) or DON (36%). The
      combination of DON+3-ADON+15-ADON was not present, while DON+15-ADON was present
      in 9% of the samples tested. The production systems did not lead to significant
      differences in mycotoxin levels, although a trend toward higher incidence and
      higher contamination was observed for the samples from the intensive and
      sustainable production systems.

PMID- 29337658
TI  - Versicolorin A is a potential indicator of aflatoxin contamination in the granary
      stored corn.
AB  - The objective of this study was to evaluate the feasibility of the predictive
      monitoring of aflatoxin B1 (AFB1) under granary conditions, since mycotoxin
      contamination of the stored grain represents an important issue. Using the
      storage test, we investigated the relationship between versicolorin A (Ver A, an
      intermediate in AFB1 biosynthesis) levels and the levels of aflatoxigenic fungi,
      and their relationship with aflatoxin production. All samples, except for one,
      were found to be contaminated with aflatoxigenic fungi using PCR analyses, while
      their AFB1 levels were not detectable before the storage test using an enzyme
      linked immunosorbent assay (ELISA) method with an LOD of 2 MUg/kg. Aflatoxigenic
      fungi levels were analysed, as well as Ver A levels prior to the accumulation of
      AFB1 (Levels were >=5 MUg/kg; the permissible levels of AFB1 in corn intended for
      direct consumption are <5 MUg/kg (EC)). Statistical analyses demonstrated that
      aflatoxin levels after both actual storage and safe storage (AFB1?5MUg/kg) times
      are significantly correlated with the Ver A levels and the changes in Ver A
      levels (DeltaVer A). Both high and variable Ver A levels were indicative of the
      vigorous metabolic activity of aflatoxigenic fungi. In contrast, steady Ver A
      levels showed that aflatoxin production by the fungi was not active. Monitoring
      Ver A levels and their changes may allow an earlier detection of harmful
      aflatoxin contamination in the stored grain. Additionally, the toxicity of Ver A
      should be further examined. The results of our study indicate that the monitoring
      of Ver A levels, even when the AFB1 levels are very low, may increase the safety
      of grain consumption, especially considering Ver A toxicity.

PMID- 29337659
TI  - Determination of five tetracyclines and their epimers by LC-MS/MS based on a
      liquid-liquid extraction with low temperature partitioning.
AB  - An LC-MS/MS method is presented for screening five tetracyclines and their
      epimers in a broad range of food products. The scope of matrices includes meat-,
      fish-, seafood-based products, various dairy ingredients, infant formulae and
      fats. The method principle is based on a liquid-liquid extraction with aqueous
      ethylenediaminetetraacetic acid (EDTA) and acetonitrile followed by a freezing
      step to promote phase separation at low temperature. After defatting with hexane,
      sample extracts were evaporated and reconstituted before injection onto the LC
      MS/MS system. The addition of oxalic acid in the aqueous mobile phase was
      mandatory to maintain good peak shape and sensitivity over the run. The screening
      is based upon a double preparation of each sample, one 'as such' and a second one
      with the analytes spiked in the sample, in order to mitigate the risk of false
      negative response. The method was validated according to the European Community
      Reference Laboratories Residues Guidelines. A total of 93 samples were included
      in the validation by two independent laboratories giving both false-negative and
      false-positive rates at 0% for all compounds. Over the last two years, 2600
      samples were analysed routinely and only one chicken sample was found above the
      regulatory limit.

PMID- 29337660
TI  - Guidance for Evaluating the Safety of Experimental Releases of Mosquitoes,
      Emphasizing Mark-Release-Recapture Techniques.
AB  - Experimental releases of mosquitoes are performed to understand characteristics
      of populations related to the biology, ability to transmit pathogens, and
      ultimately their control. In this article, we discuss considerations related to
      the safety of experimental releases of living mosquitoes, applying principles of
      good practice in vector biology that protect human health and comfort. We
      describe specific factors of experimental releases of mosquitoes that we believe
      are critical to inform institutional biosafety committees and similar review
      boards to which proposals to conduct mosquito release experiments have been
      submitted. In this study, "experimental releases" means those that do not
      significantly increase vector capacity or nuisance biting relative to the
      unperturbed natural baseline. This document specifically does not address
      releases of mosquitoes for ongoing control programs or trials of new control
      methods for which broader assessments of risk are required. It also does not
      address releases of transgenic or exotic (non-native) mosquito species, both of
      which require particular regulatory approval. Experimental releases may include
      females and males and evaluation must consider their effects based on the number
      released, their genotype and phenotype, the environment into which they are
      released, and postrelease collection activities. We consider whether increases of
      disease transmission and nuisance biting might result from proposed experimental
      releases against the backdrop of natural population size variation. We recommend
      that experimental releases be conducted in a manner that can be reasonably argued
      to have insignificant negative effects. Reviewers of proposals for experimental
      releases should expect applicants to provide such an argument based on evidence
      from similar studies and their planned activities. This document provides
      guidance for creating and evaluating such proposals.

PMID- 29337661
TI  - Maintaining Quality of Candidate Strains of Transgenic Mosquitoes for Studies in
      Containment Facilities in Disease Endemic Countries.
AB  - Transgenic mosquitoes are being developed as novel components of area-wide
      approaches to vector-borne disease control. Best practice is to develop these in
      phases, beginning with laboratory studies, before moving to field testing and
      inclusion in control programs, to ensure safety and prevent costly field testing
      of unsuitable strains. The process of identifying and developing good candidate
      strains requires maintenance of transgenic colonies over many generations in
      containment facilities. By working in disease endemic countries with target
      vector populations, laboratory strains may be developed and selected for
      properties that will enhance intended control efficacy in the next phase, while
      avoiding traits that introduce unnecessary risks. Candidate strains aiming toward
      field use must consistently achieve established performance criteria, throughout
      the process of scaling up from small study colonies to production of sufficient
      numbers for field testing and possible open release. Maintenance of a consistent
      quality can be demonstrated by a set of insect quality and insectary operating
      indicators, measured over time at predetermined intervals. These indicators:
      inform comparability of studies using various candidate strains at different
      times and locations; provide evidence of conformity relevant to compliance with
      terms of approval for regulated use; and can be used to validate some assumptions
      related to risk assessments covering the contained phase and for release into the
      environment.

PMID- 29337663
TI  - Genetically Engineered Mosquitoes for Pathogen Control.

PMID- 29337662
TI  - Studies of Transgenic Mosquitoes in Disease-Endemic Countries: Preparation of
      Containment Facilities.
AB  - Novel approaches to area-wide control of vector species offer promise as
      additional tools in the fight against vectored diseases. Evaluation of transgenic
      insect strains aimed at field population control in disease-endemic countries may
      involve international partnerships and should be done in a stepwise approach,
      starting with studies in containment facilities. The preparations of both new
      build and renovated facilities are described, including working with local and
      national regulations regarding land use, construction, and biosafety
      requirements, as well as international guidance to fill any gaps in regulation.
      The examples given are for containment categorization at Arthropod Containment
      Level 2 for initial facility design, classification of wastes, and precautions
      during shipping. Specific lessons were derived from preparations to evaluate
      transgenic (non-gene drive) mosquitoes in West and East African countries.
      Documented procedures and the use of a non-transgenic training strain for trial
      shipments and culturing were used to develop competence and confidence among the
      African facility staff, and along the chain of custody for transport. This
      practical description is offered to support other research consortia or
      institutions preparing containment facilities and operating procedures in
      conditions where research on transgenic insects is at an early stage.

PMID- 29337664
TI  - Containment Studies of Transgenic Mosquitoes in Disease Endemic Countries: The
      Broad Concept of Facilities Readiness.
AB  - Genetic strategies for large scale pest or vector control using modified insects
      are not yet operational in Africa, and currently rely on import of the modified
      strains to begin preliminary, contained studies. Early involvement of research
      teams from participating countries is crucial to evaluate candidate field
      interventions. Following the recommended phased approach for novel strategies,
      evaluation should begin with studies in containment facilities. Experiences to
      prepare facilities and build international teams for research on transgenic
      mosquitoes revealed some important organizing themes underlying the concept of
      "facilities readiness," or the point at which studies in containment may proceed,
      in sub-Saharan African settings. First, "compliance" for research with novel or
      non-native living organisms was defined as the fulfillment of all legislative and
      regulatory requirements. This is not limited to regulations regarding use of
      transgenic organisms. Second, the concept of "colony utility" was related to the
      characteristics of laboratory colonies being produced so that results of studies
      may be validated across time, sites, and strains or technologies; so that the
      appropriate candidate strains are moved forward toward field studies. Third, the
      importance of achieving "defensible science" was recognized, including that study
      conclusions can be traced back to evidence, covering the concerns of various
      stakeholders over the long term. This, combined with good stewardship of
      resources and appropriate funding, covers a diverse set of criteria for declaring
      when "facilities readiness" has been attained. It is proposed that, despite the
      additional demands on time and resources, only with the balance of and rigorous
      achievement of each of these organizing themes can collaborative research into
      novel strategies in vector or pest control reliably progress past initial
      containment studies.

PMID- 29337665
TI  - Safety of intravenous tranexamic acid in patients undergoing majororthopaedic
      surgery: a meta-analysis of randomised controlled trials.
AB  - Among the various pharmacological options to decrease peri-operative bleeding,
      tranexamic acid appears to be one of the most interesting. Several trials have
      consistently documented the efficacy of this synthetic drug in reducing the risk
      of blood loss and the need for allogeneic blood transfusion in patients
      undergoing total hip and knee arthroplasty. The safety of intravenous tranexamic
      acid in major orthopaedic surgery, particularly regarding the risk of venous
      thromboembolism, was systematically analysed in this review. A systematic search
      of the literature identified 73 randomised controlled trials involving 4,174
      patients and 2,779 controls. The raw overall incidence of venous thromboembolism
      was 2.1% in patients who received intravenous tranexamic acid and 2.0% in
      controls. A meta-analytic pooling showed that the risk of venous thromboembolism
      in tranexamic acid-treated patients was not significantly different from that of
      controls (risk difference: 0.01%, 95% confidence interval [CI]: -0.05%, 0.07%;
      risk ratio: 1.067, 95% CI: 0.760-1.496). Other severe drug-related adverse events
      occurred very rarely (0.1%). In conclusion, the results of this systematic review
      and meta-analysis show that intravenous tranexamic acid is a safe pharmacological
      treatment to reduce blood loss and transfusion requirements in patients
      undergoing major orthopaedic surgery.

PMID- 29337666
TI  - Tuning of in vivo cognate B-T cell interactions by Intersectin 2 is required for
      effective anti-viral B cell immunity.
AB  - Wiskott-Aldrich syndrome (WAS) is an immune pathology associated with mutations
      in WAS protein (WASp) or in WASp interacting protein (WIP). Together with the
      small GTPase Cdc42 and other effectors, these proteins participate in the
      remodelling of the actin network downstream of BCR engagement. Here we show that
      mice lacking the adaptor protein ITSN2, a G-nucleotide exchange factor (GEF) for
      Cdc42 that also interacts with WASp and WIP, exhibited increased mortality during
      primary infection, incomplete protection after Flu vaccination, reduced germinal
      centre formation and impaired antibody responses to vaccination. These defects
      were found, at least in part, to be intrinsic to the B cell compartment. In vivo,
      ITSN2 deficient B cells show a reduction in the expression of SLAM, CD84 or ICOSL
      that correlates with a diminished ability to form long term conjugates with T
      cells, to proliferate in vivo, and to differentiate into germinal centre cells.
      In conclusion, our study not only revealed a key role for ITSN2 as an important
      regulator of adaptive immune-response during vaccination and viral infection but
      it is also likely to contribute to a better understanding of human immune
      pathologies.

PMID- 29337668
TI  - Solving manufacturing problems for L-carnitine-L-tartrate to improve the
      likelihood of successful product scale-up.
AB  - L-carnitine-L-tartrate, a non-essential amino acid, is hygroscopic. This causes a
      problem in tablet production due to pronounced adhesion of tablets to punches. A
      33 full factorial design was adopted to suggest a tablet formulation. Three
      adsorbents were suggested (Aerosil 200, Aerosil R972, talc) to reduce stickiness
      at three concentrations (1, 3 and 5 %), and three fillers (mannitol, Avicel PH
      101, Dibasic calcium phosphate) were chosen to prepare 27 formulations.
      Micromeritic properties of formulations were studied, and tablets were prepared
      by wet granulation. Absence of picking, sticking or capping, recording of
      sufficient hardness, acceptable friability and tablet ejection force indicated
      formulation success. The resulting formulation prepared using Avicel PH 101 and 1
      % Aerosil 200 was submitted to further investigation in order to choose the most
      suitable compression conditions using a 33 full factorial design. Variables
      included compression force, tableting rate and magnesium stearate (lubricant)
      concentration. The formulation prepared at compression force of 25 kN, using 2 %
      magnesium stearate, at a production rate of 30 tablets/ minute, was found to be
      the most appropriate scale up candidate.

PMID- 29337667
TI  - Revised roles of ISL1 in a hES cell-based model of human heart chamber
      specification.
AB  - The transcription factor ISL1 is thought to be key for conveying the multipotent
      and proliferative properties of cardiac precursor cells. Here, we investigate its
      function upon cardiac induction of human embryonic stem cells. We find that ISL1
      does not stabilize the transient cardiac precursor cell state but rather serves
      to accelerate cardiomyocyte differentiation. Conversely, ISL1 depletion delays
      cardiac differentiation and respecifies nascent cardiomyocytes from a ventricular
      to an atrial identity. Mechanistic analyses integrate this unrecognized anti
      atrial function of ISL1 with known and newly identified atrial inducers. In this
      revised view, ISL1 is antagonized by retinoic acid signaling via a novel player,
      MEIS2. Conversely, ISL1 competes with the retinoic acid pathway for prospective
      cardiomyocyte fate, which converges on the atrial specifier NR2F1. This study
      reveals a core regulatory network putatively controlling human heart chamber
      formation and also bears implications for the subtype-specific production of
      human cardiomyocytes with enhanced functional properties.

PMID- 29337669
TI  - Gastroprotective effects of the isopropanol extract of Artemisia princeps and its
      gastroretentive floating tablets on gastric mucosal injury.
AB  - In this study, we investigated the gastroprotective effect of an isopropanol
      extract from the aerial parts of Artemisia princeps (IPAP) and developed a
      gastroretentive floating tablet of IPAP (IPAP-FR) for maximized local
      gastroprotective effects. Pre-treatment with IPAP ameliorated the gastric mucosal
      hemorrhagic lesions in ethanol/HCl- or indomethacin- treated rats. IPAP decreased
      mucosal hemorrhage of gastric ulcers induced by ethanol or indomethacin plus
      pyloric ligation in rats. The optimized floating tablet, IPAP-FR, floated on
      medium surface with more sustained eupatilin release compared to the non-floating
      control tablet. X-ray photographs in beagle dogs showed that IPAPFR was retained
      for > 2 h in the stomach. In the ethanol-induced gastric ulcer rat model, the
      gastric hemorrhagic lesion was improved more substantially with IPAP-FR compared
      to the non-floating control tablet. Based on these data, our data suggest that
      IPAP-FR has an improved therapeutic potential for the treatment of gastric ulcer.

PMID- 29337670
TI  - Sustained release biodegradable solid lipid microparticles: Formulation,
      evaluation and statistical optimization by response surface methodology.
AB  - For preparing nebivolol loaded solid lipid microparticles (SLMs) by the solvent
      evaporation microencapsulation process from carnauba wax and glyceryl
      monostearate, central composite design was used to study the impact of
      independent variables on yield (Y1), entrapment efficiency (Y2) and drug release
      (Y3). SLMs having a 10-40 MUm size range, with good rheological behavior and
      spherical smooth surfaces, were produced. Fourier transform infrared
      spectroscopy, differential scanning calorimetry and X-ray diffractometry pointed
      to compatibility between formulation components and the zeta-potential study
      confirmed better stability due to the presence of negative charge (-20 to -40
      mV). The obtained outcomes for Y1 (29-86 %), Y2 (45-83 %) and Y3 (49-86 %) were
      analyzed by polynomial equations and the suggested quadratic model were
      validated. Nebivolol release from SLMs at pH 1.2 and 6.8 was significantly (p <
      0.05) affected by lipid concentration. The release mechanism followed Higuchi and
      zero order models, while n > 0.85 value (Korsmeyer- Peppas) suggested slow
      erosion along with diffusion. The optimized SLMs have the potential to improve
      nebivolol oral bioavailability.

PMID- 29337671
TI  - Spectrophotometric method for simultaneous determination of valsartan and
      substances from the group of statins in binary mixtures.
AB  - Applicability of derivative spectrophotometry for the determination of valsartan
      in the presence of a substance from the group of statins was checked. The
      obtained results indicate that the proposed method may be effective by using
      appropriate derivatives: for valsartan and fluvastatin - D1, D2 and D3, for
      valsartan and pravastatin - D1 and D3, for valsartan and atorvastatin - D2 and
      D3. The method was characterized by high sensitivity and accuracy. Linearity was
      maintained in the following ranges: 9.28-32.48 mg mL-1 for valsartan, 8.16-28.56
      mg mL-1 f or fluvastatin, 14.40-39.90 mg mL-1 for atorvastatin and 9.60-48.00 mg
      mL-1 for pravastatin. Determination coefficients were in the range of 0.989-0.999
      depending on the analyte and the order of derivative. The precision of the method
      was high with RSD from 0.1 to 2.5 % and recovery of individual components was
      within the range of 100 +/- 5 %. The developed method was successfully applied to
      the determination of valsartan combined with fluvastatin, atorvastatin and
      pravastatin in laboratory prepared mixtures and in pharmaceutical preparations.

PMID- 29337672
TI  - Influence of plasma on the physical properties of ointments with quercetin.
AB  - Effects of two independent variables - the content of quercetin (0 or 1 or 1.5 or
      5 %) and the content of plasma (0 or 2 or 4 or 6 %) - on the organoleptic
      properties and rheological parameters of model formulations prepared on an
      amphiphilic base were estimated. The consistency of all ointments was uniform,
      and the content of quercetin and plasma lay within the predefined range. Tested
      ointments are non-Newtonian systems. The content of quercetin and plasma was
      found to have a significant effect on the rheological properties of the
      ointments. An increase in the content of plasma in ointments was accompanied by a
      significant increase in their hardness, viscosity and shear stress and a
      reduction of their spreadability. The best rheological properties were shown by
      formulation F-3, containing 1.5 % of quercetin and 2 % of plasma.

PMID- 29337673
TI  - Evaluation of immunomodulatory effects of lamotrigine in BALB/c mice.
AB  - Modulation of the immune system has recently been shown to be involved in the
      pharmacological effects of old antiepileptic drugs and in the pathogenesis of
      epilepsy. Therefore, the most recent guidelines for immunotoxicological
      evaluation of drugs were consulted to investigate the immunomodulatory effects of
      lamotrigine, a newer antiepileptic drug, in BALB/c mice. These included the in
      vivo effects of lamotrigine on delayed-type hypersensitivity (DTH) response to
      sheep red blood cell (SRBC) antigens, hemagglutination titer assays and
      hematological changes. In vitro effects of lamotrigine on ConA-induced splenocyte
      proliferation and cytokine secretion were assessed. The results showed that
      lamotrigine treatment significantly increased the DTH response to SRBC in the
      mouse model of this study. This was accompanied by a significant increase in
      relative monocyte and neutrophil counts and in spleen cellularity. Lamotrigine
      significantly inhibited ConA-induced splenocyte proliferation in vitro and it
      significantly inhibited IL-2 and TNF-alpha secretion in ConA-stimulated
      splenocytes. In conclusion, the results demonstrated significant immunomodulatory
      effects of lamotrigine in BALB/c mice. These data could expand the understanding
      of lamotrigine-induced adverse reactions and its role in modulating the immune
      system in epilepsy.

PMID- 29337674
TI  - A study on blocking store-operated Ca2+ entry in pulmonary arterial smooth muscle
      cells with xyloketals from marine fungi.
AB  - In this study, the effect of four xyloketals 1-4 on store-operated calcium entry
      (SOCE) was investigated in primary distal pulmonary arterial smooth muscle cells
      (PASMCs) isolated from mice. The results showed that xyloketal A (1), an unusual
      ketal with C-3 symmetry, exhibited strong SOCE blocking activity. Secretion of
      interleukin-8 (IL-8) was also inhibited by xyloketal A. The parallel artificial
      membrane permeability assay (PAMPA) of 1-4 suggested that these xyloketals
      penetrated easily through the cell membrane. Moreover, the molecular docking
      study of xyloketal A with activation region of the stromal interaction molecule
      (STIM) 1 and the calcium release-activated calcium modulator (ORAI) 1 (STIM1
      ORAI1) protein complex, the key domain of SOCE, revealed that xyloketal A
      exhibited a noncovalent interaction with the key residue lysine 363 (LYS363) in
      the identified cytosolic regions in STIM1-C. These findings provided useful
      information about xyloketal A as a SOCE inhibitor for further evaluation.

PMID- 29337675
TI  - Synthesis and evaluation of antitumor activity of new 4-substituted thieno[3,2
      d]pyrimidine and thienotriazolopyrimidine derivatives.
AB  - 3-Methyl-6-phenyl-2-thioxo-2,3-dihydrothieno[3,2-d]pyrimidin- 4(1H)-one (2), on
      treatment with phosphorous oxychoride, affored 4-chloro-3-methyl-6-phenyl 
      thieno[3,2-d]pyrimidine- 2(3H)-thione (3). A series of novel 6-phenyl-thieno[3,2
      d]pyrimidine derivatives 4-9 bearing different functional groups were synthesized
      via treatment of compound 3 with different reagents. On the other hand, compound
      2 was used to synthesize ethyl-[(3-methyl-6-phenyl-2-thioxo-2,3-dihydrothieno[
      3,2-d]pyrimidin-4-yl)-oxy]acetate (10), 2-hydrazinyl- -3-methyl-6-phenyl
      thieno[3,2-d]pyrimidin-4(3H)-one (11), 3-methyl-2-(methyl-sulfanyl)-6-phenyl
      thieno[3,2-d]pyrimidin- 4(3H)-one (12) and N-(phenyl)/4-chlorophenyl or methoxy-
      phenyl)-2-[(3-methyl-4-oxo-6-phenyl-3,4-dihydrothieno[ 3,2-d]pyrimidin-2-yl)
      sulfanyl]-acetamide (13a-c). In addition, compound 12 was used to synthesize
      thieno[1,2,4] triazolopyrimidine derivatives 14 and 15 and 3-methyl-2-(methyl
      sulfonyl)-6-phenyl-thieno[3,2-d]pyrimidin-4(3H)-one (16) through the reaction
      with the respective reagents. Moreover, the reaction of 16 with 4
      phenylenediamine gave 2-[(4-aminophenyl)-amino]-3-methyl-6-phenyl-thieno[3,2-d]
      pyrimidin-4(3H)-one (17), which reacted with methanesulfonyl chloride to afford N
      {4-[(3-methyl-4-oxo-6-phenyl-3H,4H- -thieno[3,2-d]pyrimidin-2-yl)-amino]phenyl}
      methanesulfonamide (18). The majority of the newly synthesized compounds
      displayed potent anticancer activity, comparable to that of doxorubicin, on three
      human cancer cell lines, including the human breast adenocarcinoma cell line (MCF
      7), cervical carcinoma cell line (HeLa) and colonic carcinoma cell line (HCT-
      116). Compounds 18, 13b and 10 were nearly as active as doxorubicin whereas
      compounds 6, 7b and 15 exhibited marked growth inhibition, but still lower than
      doxorubicin.

PMID- 29337677
TI  - Synthesis and cytotoxicity evaluation of thiazole derivatives obtained from 2
      amino-4,5,6,7-tetrahydrobenzo[b]thiophene- 3-carbonitrile.
AB  - Reactivity of 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3- carbonitrile towards
      thioglycolic acid resulted in thiazole derivative 1. The latter reacted with
      different chemical reagents to give thiazole, pyrano[2,3-d]thiazole and thiazolo[
      4,5-d]thiazole derivatives. Cytotoxicity effects of the newly synthesized
      products against six cancer cell lines, namely, human gastric cancer (NUGC),
      human colon cancer (DLD- 1), human liver cancer (HA22T and HEPG-2), human breast
      cancer (MCF) and nasopharyngeal carcinoma (HONE-1) as well as against a normal
      fibroblast cell (WI-38) were evaluated. The study showed that the 4,5,6,7
      tetrahydrobenzo[ b] thiophene derivatives 6a, 7, 8a,b, 9b and 10b,c w ere t he
      most active compounds. Their potencies were attributed to the presence of the
      electron withdrawing groups.

PMID- 29337676
TI  - Alkyl polyglucoside vs. ethoxylated surfactant-based microemulsions as vehicles
      for two poorly water-soluble drugs: physicochemical characterization and in vivo
      skin performance.
AB  - Two types of biocompatible surfactants were evaluated for their capability to
      formulate skin-friendly/non-irritant microemulsions as vehicles for two poorly
      water-soluble model drugs differing in properties and concentrations: alkyl
      polyglucosides (decyl glucoside and caprylyl/capryl glucoside) and ethoxylated
      surfactants (glycereth-7-caprylate/ caprate and polysorbate 80). Phase behavior,
      structural inversion and microemulsion solubilization potential for sertaconazole
      nitrate and adapalene were found to be highly dependent on the surfactants
      structure and HLB value. Performed characterization (polarized light microscopy,
      pH, electrical conductivity, rheological, FTIR and DSC measurements) indicated a
      formulation containing glycereth- 7-caprylate/caprate as suitable for
      incorporation of both drugs, whereas alkyl polyglucoside-based systems did not
      exhibit satisfying solubilization capacity for sertaconazole nitrate. Further,
      monitored parameters were strongly affected by sertaconazole nitrate
      incorporation, while they remained almost unchanged in adapalene-loaded vehicles.
      In addition, results of the in vivo skin performance study supported acceptable
      tolerability for all investigated formulations, suggesting selected
      microemulsions as promising carriers worth exploring further for effective skin
      delivery of model drugs.

PMID- 29337678
TI  - Salivary sCD14 as a potential biomarker of dental caries activity in adults.
AB  - CD14 is a co-receptor involved in the recognition of Gram-negative and Gram
      positive bacteria, the latter known to cause dental caries. The aim of this study
      was to determine whether soluble CD14 (sCD14) in saliva was associated with
      caries activity and the collection method from the saliva. The study included 55
      participants aged 20 to 40 years, 30 with dental caries and 25 caries-free
      controls. We collected 110 saliva samples in total, 55 of resting saliva and 55
      of mechanically stimulated saliva. Median levels of sCD14, measured with a matrix
      matched enzyme-linked immunosorbent assay (ELISA), were higher in the caries
      active than in the caries-free group in either resting (203.3 vs.167.9 ng mL-1;
      P<0.01) or stimulated saliva (201 vs.105.7 ng mL-1; P<0.01). The resting salivary
      flow rate was lower in the caries-active than caries-free group (0.61+/-0.42 vs.
      0.98+/-0.52 mL min-1; P<0.01). Hyposalivation was observed only in the caries
      active group (10 and 13 % in stimulated and resting saliva, respectively). Higher
      salivary sCD14 levels and secretion rates were clearly associated with dental
      caries and resting saliva. Future studies should focus on the clinical utility of
      salivary sCD14 as a potential biomarker and predictor of future caries events.

PMID- 29337679
TI  - The effects of physical activity on chronic subclinical systemic inflammation.
AB  - Chronic subclinical systemic inflammation (CSSI) is a pathogenic event and a
      common risk factor for many noncommunicable diseases like atherosclerosis,
      metabolic syndrome, cardiovascular disease, insulin resistance and type 2
      diabetes, cancer, and obstructive lung disease. On the other hand, regular
      physical activity has been found to reduce this risk. Many studies of different
      design were conducted to assess the association between inflammatory mediators as
      markers of CSSI and regular physical activity. The aim of this review was to
      present the current level of evidence and understanding of potential mechanisms
      by which physical activity reduces inflammatory mediators involved in CSSI and
      the types of physical activity required for the expected effect. We have found
      that observational studies consistently report a positive association between
      regular physical activity and lower CSSI, but the design of these studies does
      not allow to infer a causal relationship. Interventional studies, in contrast,
      were not consistent about the causal relationship between regular physical
      activity and lower CSSI. The problem in interpreting these results lies in
      significant differences between these interventional studies in their design,
      sample size, study population, and intervention itself (intensity and extent,
      follow up, weight loss). We can conclude that the scientific community has to
      invest a significant effort into high-quality interventional trials focused on
      finding the type, intensity, and extent of physical activity that would produce
      the most favourable effect on CSSI.

PMID- 29337680
TI  - In vitro assessment of the cytotoxic, DNA damaging, and cytogenetic effects of
      hydroquinone in human peripheral blood lymphocytes.
AB  - This study investigated the mechanisms of hydroquinone toxicity and assessed the
      relationships between its cytotoxic, genotoxic, and cytogenetic effects tested at
      8, 140, and 280 MUg mL-1 in human peripheral blood lymphocytes exposed for 24 h.
      The outcomes of the treatments were evaluated using the apoptosis/necrosis assay,
      the alkaline comet assay, and the cytokinesis-block micronucleus (CBMN) cytome
      assay. The tested hydroquinone concentrations produced relatively weak
      cytotoxicity in resting lymphocytes, which mostly died via apoptosis.
      Hydroquinone's marked genotoxic effects were detected using the alkaline comet
      assay. Significantly decreased values of all comet parameters compared to
      controls indicated specific mechanisms of hydroquinone-DNA interactions. Our
      results suggest that the two higher hydroquinone concentrations possibly led to
      cross-linking and adduct formation. Increased levels of DNA breakage measured
      following exposure to the lowest concentration suggested mechanisms related to
      oxidative stress and inhibition of topoisomerase II. At 8 MUg mL-1, hydroquinone
      did not significantly affect MN formation. At 140 and 280 MUg mL-1, it completely
      blocked lymphocyte division. The two latter concentrations also led to
      erythrocyte stabilization and prevented their lysis. At least two facts
      contribute to this study's relevance: (I) this is the first study that quantifies
      the degree of reduction in total comet area measured in lymphocyte DNA after
      hydroquinone treatment, (II) it is also the first one on a lymphocyte model that
      adopted the "cytome" protocol in an MN assay and found that lymphocytes exposure
      even to low hydroquinone concentration resulted in a significant increase of
      nuclear bud frequency. Considering the limitations of the lymphocyte model, which
      does not possess intrinsic metabolic activation, in order to unequivocally prove
      the obtained results further studies using other appropriate cell lines are
      advised.

PMID- 29337681
TI  - Dissipation dynamics of terbuthylazine in soil during the maize growing season.
AB  - Ever since terbuthylazine (TBA) replaced atrazine in herbicide crop treatment,
      its much greater persistence has raised considerable environmental concern. The
      aim of our field experiment was to establish the dissipation dynamics of TBA and
      its degradation product desethylterbuthylazine (DET) in soil over five months of
      maize growth. We applied TBA as part of pre-emergent treatment in the regular and
      double-the-regular amounts. Soil samples were collected periodically at the
      following depths: 0-10 cm, 10-20 cm, 20-30 cm, and 30-50 cm. For TBA and DET soil
      residue analysis we used microwave-assisted extraction with methanol, followed by
      HPLC-UV/DAD. Regardless of the application rate, more than 80 % of the applied
      TBA dissipated from the first 50 cm of soil in the two months after herbicide
      application and 120 mm of rainfall. Three months later (at maize harvest), less
      than 4 % of total TBA remained in the soil, mostly in the top 20 cm rich with
      organic carbon on which TBA is likelier to adsorb. The loss of TBA from soil
      coincided with the rise in DET, especially the top soil layers, during the
      periods of low rainfall and highest soil temperatures. This points to
      biodegradation as the main route of TBA dissipation in humic soils. The applied
      amount had no significant effect on TBA dissipation in the top (humic) layers,
      but in the layers with less than 1 % of organic carbon, it was higher when the
      doublethe- regular dose was applied.

PMID- 29337682
TI  - Adverse effects of organophosphorus pesticides on the liver: a brief summary of
      four decades of research.
AB  - Organophosphorus pesticides (OPs) are widely used volatile pesticides that have
      harmful effects on the liver in acute and chronic exposures. This review article
      summarises and discusses a wide collection of studies published over the last 40
      years reporting on the effects of OPs on the liver, in an attempt to propose
      general mechanisms of OP hepatotoxicity and possible treatment. Several key
      biological processes have been reported as involved in OP-induced hepatotoxicity
      such as disturbances in the antioxidant defence system, oxidative stress,
      apoptosis, and mitochondrial and microsomal metabolism. Most studies show that
      antioxidants can attenuate oxidative stress and the consequent changes in liver
      function. However, few studies have examined the relationship between OP
      structures and the severity and mechanism of their action. We hope that future in
      vitro, in vivo, and clinical trials will answer the remaining questions about the
      mechanisms of OP hepatotoxicity and its management.

PMID- 29337683
TI  - How protein coronas determine the fate of engineered nanoparticles in biological
      environment.
AB  - Nanomedicine is a booming medical field that utilises nanoparticles (NPs) for the
      development of medicines, medical devices, and diagnostic tools. The behaviour of
      NPs in vivo may be quite complex due to their interactions with biological
      molecules. These interactions in biological fluids result in NPs being enveloped
      by dynamic protein coronas, which serve as an interface between NPs and their
      environment (blood, cell, tissue). How will the corona interact with this
      environment will depend on the biological, chemical, and physical properties of
      NPs, the properties of the proteins that make the corona, as well as the
      biological environment. This review summarises the main characteristics of
      protein corona and describes its dynamic nature. It also presents the most common
      analytical methods to study the corona, including examples of protein corona
      composition for the most common NPs used in biomedicine. This knowledge is
      necessary to design NPs that will create a corona with a desired efficiency and
      safety in clinical use.

PMID- 29337684
TI  - Hepatotoxicity associated with statins.
AB  - Treatment with statins is known all over the world. They are generally considered
      safe at therapeutic doses. Nevertheless, clinical trials are not enough to assess
      their scarce adverse effects such as idiosyncratic drug induced liver injury
      (DILI). Due to some conditions, such as concomitant usage (drug-drug interaction
      using an identical metabolising enzyme) and genetic polymorphisms, there is an
      increasing concern about their safety. Hepatotoxicity and rhabdomyolysis have
      begun to appear in published studies. Most of investigations have focused on both
      these adverse effects and mechanisms of drug induced toxicity. The present review
      has attempted to compile almost all of the existing studies on the hepatotoxicity
      of statins but not rhabdomyolysis. The aim of our study is to provide an overview
      of the studies on the statin-associated hepatotoxicity and to discuss the
      published studies. The researchers are of the opinion that the research on this
      topic is incomplete but extremely necessary.

PMID- 29337685
TI  - Radiological risk assessment: an overview of the ERICA Integrated Approach and
      the ERICA Tool use.
AB  - The ERICA project (Environmental Risk from Ionising Contaminants: Assessment and
      Management) was co-funded by the European Union as part of the 6th Framework
      Programme (FP EURATOM). The project was carried out between 2004 and 2007 as the
      collective work of 15 organisations in seven European countries. Two significant
      outputs of the project are the ERICA Integrated Approach and the ERICA Tool. The
      ERICA Integrated Approach consists of three elements: assessment, risk
      characterisation and management. The ERICA Tool is a practical implementation of
      the assessment component of the ERICA Integrated Approach and has a three-tier
      structure. The aim of this review paper is to give a concise overview of ERICA
      project outputs and their structure, updates done since their first release in
      2007, as well as to provide a context for their practical application in
      environmental radiation protection and radiological risk assessments for various
      engineering scenarios.

PMID- 29337686
TI  - Forgotten public health impacts of cancer - an overview.
AB  - Cancer is one of the diseases of greatest concern in developed countries and much
      effort has been invested in discovering and developing therapeutics for curing
      cancer. Despite the improvements in antineoplastic therapeutics in the last
      decades, cancer is still one of the most harmful diseases worldwide. The global
      burden of cancer also implies financial costs: these can be direct costs, such as
      those related to treatment, care, and rehabilitation and indirect, which include
      the loss of economic output due to missed work (morbidity costs) and premature
      death (mortality costs). There are also hidden costs such as health insurance
      premiums and nonmedical expenses that are worth noting. This paper intends to
      present an overview of the generally forgotten impacts that the increasing number
      of cancer cases can have on the environment, workers who handle antineoplastic
      drugs, and health services. The knowledge available of each of the impacts will
      be addressed and discussed regarding the expected development. Overall, lessons
      learnt reflect on the impact of cancer through aspects not commonly evidenced in
      the literature or even considered in socio-economic analysis, in part due to the
      fact that these are difficult to contemplate in direct and indirect cancer costs
      already defined. Attention may be drawn to the need of continuous investment in
      prevention to reduce the negative impact on the environment, and in the health of
      workers who handle antineoplastic drugs for patients' treatment.

PMID- 29337687
TI  - Comparison of the solid phase and liquid-liquid extraction methods for methadone
      determination in human serum and whole blood samples using gas
      chromatography/mass spectrometry.
AB  - The aim of this study was to determine the optimal biological sample and the
      optimal extraction technique for monitoring methadone concentrations in
      biological samples. We analysed methadone in serum and whole blood samples using
      gas chromatography/mass spectrometry (GC/MS). Before analysis, we compared five
      solid-phase extraction (SPE) and two liquid-liquid extraction (LLE) methods and
      determined that SPE with Supelco LC-18 in serum yielded the best extraction
      efficiency. The limit of detection was 10 ng mL-1 and the limit of quantification
      25 ng mL-1. Correlation coefficient was over 0.999 for the methadone calibration
      curve in linear range from 50 to 2000 ng mL-1. Intra and inter-day accuracy and
      precision of the method was satisfactory. The method was successfully applied for
      determining serum methadone in patients on maintenance therapy.

PMID- 29337688
TI  - Interaction of the middle domains stabilizes Hsp90alpha dimer in a closed
      conformation with high affinity for p23.
AB  - The human genome encodes two highly similar cytosolic Hsp90 proteins called
      isoforms Hsp90alpha and Hsp90beta. Of the 300 client proteins for Hsp90
      identified so far only a handful interact specifically with one Hsp90 isoform.
      Here we report for the first time that Hsp90 cochaperone p23 binds preferentially
      to Hsp90alpha and that this interaction is mediated by the middle domain of
      Hsp90alpha. Based on the homology modeling, we infer that the middle domains in
      the Hsp90alpha dimer bind stronger with each other than in the Hsp90beta dimer.
      Therefore, compared to Hsp90beta, Hsp90alpha may adopt closed conformation more
      easily. Hsp90 interacts with p23 in the closed conformation. Hsp90alpha binds
      human recombinant p23 about three times stronger than Hsp90beta but with
      significantly smaller exothermic enthalpy as determined by isothermal titration
      calorimetry of direct binding between the purified proteins. As p23 binds to
      Hsp90 in a closed conformation, stabilization of the Hsp90alpha dimer in the
      closed conformation by its middle domains explains preference of p23 to this
      Hsp90 isoform.

PMID- 29337689
TI  - Abeta42 oligomers impair the bioenergetic activity in hippocampal synaptosomes
      derived from APP-KO mice.
AB  - Employing hippocampal synaptosomes from amyloid precursor protein (APP)-deleted
      mice we analyzed the immediate effects of amyloid beta peptide 42 (Abeta42)
      peptide in its oligomeric or fibrillar assembly or of soluble amyloid precursor
      protein alpha (sAPPalpha) protein on their bioenergetic activity. Upon
      administration of oligomeric Abeta42 peptide for 30 min we observed a robust
      decrease both in mitochondrial activity and in mitochondrial membrane potential
      (MMP). In contrast the respective fibrillary or scrambled peptides showed no
      effect, indicating that inhibition strictly depends on the oligomerization status
      of the peptide. Hippocampal synaptosomes from old APP-KO mice revealed a further
      reduction of their already impaired bioenergetic activity upon incubation with 10
      MUm Abeta42 peptide. In addition we evaluated the influence of the sAPPalpha
      protein on mitochondrial activity of hippocampal synaptosomes derived from young
      or old APP-KO animals. In neither case 20 nm nor 200 nm sAPPalpha protein had an
      effect on mitochondrial metabolic activity. Our findings demonstrate that
      hippocampal synaptosomes derived from APP-KO mice are a most suitable model
      system to evaluate the impact of Abeta42 peptide on its bioenergetic activity and
      to further elucidate the molecular mechanisms underlying the impairments by
      oligomeric Abeta42 on mitochondrial function. Our data demonstrate that
      extracellular Abeta42 peptide is taken up into synaptosomes where it immediately
      attenuates mitochondrial activity.

PMID- 29337690
TI  - Molecular determinants of Drosophila immunophilin FKBP39 nuclear localization.
AB  - FK506-binding proteins (FKBPs) belong to a distinct class of immunophilins that
      interact with immunosuppressants. They use their peptidyl-prolyl isomerase
      (PPIase) activity to catalyze the cis-trans conversion of prolyl bonds in
      proteins during protein-folding events. FKBPs also act as a unique group of
      chaperones. The Drosophila melanogaster peptidyl-prolyl cis-trans isomerase FK506
      binding protein of 39 kDa (FKBP39) is thought to act as a transcriptional
      modulator of gene expression in 20-hydroxyecdysone and juvenile hormone signal
      transduction. The aim of this study was to analyze the molecular determinants
      responsible for the subcellular distribution of an FKBP39-yellow fluorescent
      protein (YFP) fusion construct (YFP-FKBP39). We found that YFP-FKBP39 was
      predominantly nucleolar. To identify the nuclear localization signal (NLS), a
      series of YFP-tagged FKBP39 deletion mutants were prepared and examined in vivo.
      The identified NLS signal is located in a basic domain. Detailed mutagenesis
      studies revealed that residues K188 and K191 are crucial for the nuclear
      targeting of FKBP39 and its nucleoplasmin-like (NPL) domain contains the sequence
      that controls the nucleolar-specific translocation of the protein. These results
      show that FKBP39 possesses a specific NLS in close proximity to a putative helix
      turn-helix (HTH) motif and FKBP39 may bind DNA in vivo and in vitro.

PMID- 29337691
TI  - The neutral sphingomyelinase 2 in T cell receptor signaling and polarity.
AB  - By hydrolyzing its substrate sphingomyelin at the cytosolic leaflet of cellular
      membranes, the neutral sphingomyelinase 2 (NSM2) generates microdomains which
      serve as docking sites for signaling proteins and thereby, functions to regulate
      signal relay. This has been particularly studied in cellular stress responses
      while the regulatory role of this enzyme in the immune cell compartment has only
      recently emerged. In T cells, phenotypic polarization by co-ordinated
      cytoskeletal remodeling is central to motility and interaction with endothelial
      or antigen-presenting cells during tissue recruitment or immune synapse
      formation, respectively. This review highlights studies adressing the role of
      NSM2 in T cell polarity in which the enzyme plays a major role in regulating
      cytoskeletal dynamics.

PMID- 29337692
TI  - Generation of superoxide and hydrogen peroxide by side reactions of mitochondrial
      2-oxoacid dehydrogenase complexes in isolation and in cells.
AB  - Mitochondrial 2-oxoacid dehydrogenase complexes oxidize 2-oxoglutarate, pyruvate,
      branched-chain 2-oxoacids and 2-oxoadipate to the corresponding acyl-CoAs and
      reduce NAD+ to NADH. The isolated enzyme complexes generate superoxide anion
      radical or hydrogen peroxide in defined reactions by leaking electrons to oxygen.
      Studies using isolated mitochondria in media mimicking cytosol suggest that the 2
      oxoacid dehydrogenase complexes contribute little to the production of superoxide
      or hydrogen peroxide relative to other mitochondrial sites at physiological
      steady states. However, the contributions may increase under pathological
      conditions, in accordance with the high maximum capacities of superoxide or
      hydrogen peroxide-generating reactions of the complexes, established in isolated
      mitochondria. We assess available data on the use of modulations of enzyme
      activity to infer superoxide or hydrogen peroxide production from particular 2
      oxoacid dehydrogenase complexes in cells, and limitations of such methods to
      discriminate specific superoxide or hydrogen peroxide sources in vivo.

PMID- 29337693
TI  - In vitro reconstitution and biochemical characterization of human phospholipid
      scramblase 3: phospholipid specificity and metal ion binding studies.
AB  - Human phospholipid scramblase 3 (hPLSCR3) is a single pass transmembrane protein
      that plays a vital role in fat metabolism, mitochondrial function, structure,
      maintenance and apoptosis. The mechanism of action of scramblases remains still
      unknown, and the role of scramblases in phospholipid translocation is heavily
      debated. hPLSCR3 is the only member of scramblase family localized to
      mitochondria and is involved in cardiolipin translocation at the mitochondrial
      membrane. Direct biochemical evidence of phospholipid translocation by hPLSCR3 is
      yet to be reported. Functional assay in synthetic proteoliposomes upon Ca2+ and
      Mg2+ revealed that, apart from cardiolipin, recombinant hPLSCR3 translocates
      aminophospholipids such as NBD-PE and NBD-PS but not neutral phospholipids. Point
      mutation in hPLSCR3 (F258V) resulted in decreased Ca2+ binding affinity.
      Functional assay with F258V-hPLSCR3 led to ~50% loss in scramblase activity in
      the presence of Ca2+ and Mg2+. Metal ion-induced conformational changes were
      monitored by intrinsic tryptophan fluorescence, circular dichroism, surface
      hydrophobicity changes and aggregation studies. Our results revealed that Ca2+
      and Mg2+ bind to hPLSCR3 and trigger conformational changes mediated by
      aggregation. In summary, we suggest that the metal ion-induced conformational
      change and the aggregation of the protein are essential for the phospholipid
      translocation by hPLSCR3.

PMID- 29337694
TI  - Magnetic and structural depth profiles of Heusler alloy Co2FeAl0.5Si0.5 epitaxial
      films on Si(1 1 1).
AB  - The depth-resolved chemical structure and magnetic moment of [Formula: see text],
      thin films grown on Si(1 1 1) have been determined using x-ray and polarized
      neutron reflectometry. Bulk-like magnetization is retained across the majority of
      the film, but reduced moments are observed within 45[Formula: see text] of the
      surface and in a 25[Formula: see text] substrate-interface region. The reduced
      moment is related to compositional changes due to oxidation and diffusion, which
      are further quantified by elemental profiling using electron microscopy with
      electron energy loss spectroscopy. The accuracy of structural and magnetic depth
      profiles obtained from simultaneous modeling is discussed using different
      approaches with different degree of constraints on the parameters. Our approach
      illustrates the challenges in fitting reflectometry data from these multi
      component quaternary Heusler alloy thin films.

PMID- 29337696
TI  - High-pressure structural and vibrational properties of monazite-type BiPO4,
      LaPO4, CePO4, and PrPO4.
AB  - Monazite-type BiPO4, LaPO4, CePO4, and PrPO4 have been studied under high
      pressure by ab initio simulations and Raman spectroscopy measurements in the
      pressure range of stability of the monazite structure. A good agreement between
      experimental and theoretical Raman-active mode frequencies and pressure
      coefficients has been found which has allowed us to discuss the nature of the
      Raman-active modes. Besides, calculations have provided us with information on
      how the crystal structure is modified by pressure. This information has allowed
      us to determine the equation of state and the isothermal compressibility tensor
      of the four studied compounds. In addition, the information obtained on the
      polyhedral compressibility has been used to explain the anisotropic axial
      compressibility and the bulk compressibility of monazite phosphates. Finally, we
      have carried out a systematic discussion on the high-pressure behavior of the
      four studied phosphates in comparison to results of previous studies.

PMID- 29337697
TI  - Enhanced second harmonic generation from a plasmonic Fano structure subjected to
      an azimuthally polarized light beam.
AB  - We show that an azimuthally polarized beam (APB) excitation of a plasmonic Fano
      structure made by coupling a split-ring resonator (SRR) to a nanoarc can enhance
      second harmonic generation (SHG). Strikingly, an almost 30 times enhancement in
      SHG peak intensity can be achieved when the excitation is switched from a
      linearly polarized beam (LPB) to an APB. We attribute this significant
      enhancement of SHG to the corresponding increase in the local field intensity at
      the fundamental frequency of SHG, resulting from the improved conversion
      efficiency between the APB excitation and the plasmonic modes of the Fano
      structure. We also show that unlike LPB, APB excitation creates a symmetric SHG
      radiation pattern. This effect can be understood by considering an interference
      model in which the APB can change the total SHG far-field radiation by modifying
      the amplitudes and phases of two waves originating from the individual SRR and
      nanoarc of the Fano structure.

PMID- 29337695
TI  - Automated fabrication of photopatterned gelatin hydrogels for organ-on-chips
      applications.
AB  - Organ-on-chip platforms aim to improve preclinical models for organ-level
      responses to novel drug compounds. Heart-on-a-chip assays in particular require
      tissue engineering techniques that rely on labor-intensive photolithographic
      fabrication or resolution-limited 3D printing of micropatterned substrates, which
      limits turnover and flexibility of prototyping. We present a rapid and automated
      method for large scale on-demand micropatterning of gelatin hydrogels for organ
      on-chip applications using a novel biocompatible laser-etching approach. Fast and
      automated micropatterning is achieved via photosensitization of gelatin using
      riboflavin-5'phosphate followed by UV laser-mediated photoablation of the gel
      surface in user-defined patterns only limited by the resolution of the 15 MUm
      wide laser focal point. Using this photopatterning approach, we generated
      microscale surface groove and pillar structures with feature dimensions on the
      order of 10-30 MUm. The standard deviation of feature height was 0.3 MUm,
      demonstrating robustness and reproducibility. Importantly, the UV-patterning
      process is non-destructive and does not alter gelatin micromechanical properties.
      Furthermore, as a quality control step, UV-patterned heart chip substrates were
      seeded with rat or human cardiac myocytes, and we verified that the resulting
      cardiac tissues achieved structural organization, contractile function, and long
      term viability comparable to manually patterned gelatin substrates. Start-to
      finish, UV-patterning shortened the time required to design and manufacture
      micropatterned gelatin substrates for heart-on-chip applications by up to 60%
      compared to traditional lithography-based approaches, providing an important
      technological advance enroute to automated and continuous manufacturing of organ
      on-chips.

PMID- 29337698
TI  - Fe and Co NMR studies of magnetoelectric Co2 Y-type hexaferrite BSCFAO.
AB  - The Fe3+ and Co2+ NMR spectra for Ba0.3Sr1.7Co2(Fe0.96Al0.04)12O22 (BSCFAO) and
      Ba0.3Sr1.7Co2Fe12O22 (BSCFO) were obtained in a zero magnetic field at a low
      temperature. We observed change in the enhancement effect of the NMR signals
      depending on the setting field, which was varied when applied along the b-axis
      and then turned off before the measurement was taken. The experimental results
      indicate that the magnetic structure changes from an alternating longitudinal
      cone to a transverse cone when the setting field is 250 mT. They also show that
      the spins of Co2+ ions together with those of Fe3+ ions constitute a part of the
      overall magnetic structure and that the substitution of Al3+ for Fe3+ weakens the
      magnetic anisotropy within the easy plane. From a comparison of the enhancement
      factors of the Fe3+ NMR obtained with the RF pulse applied along the a-axis and
      the c-axis, we found that the magnetic easy plane anisotropy is approximately 16
      times greater than the anisotropy within the easy plane. No changes of the NMR
      spectra were observed under an electric field of 1.2 MV m-1.

PMID- 29337700
TI  - Increased resistance to tissue plasminogen activator-induced fibrinolysis in
      healthy subjects from Thailand.
AB  - : There is significant variability in blood coagulation among world populations.
      In particular, there may exist important differences in regulation of the
      fibrinolytic system in Asian populations that contribute to diseases of
      thrombosis and hemostasis. To investigate this issue, we compared fibrinogen
      concentration, plasma clot formation, and fibrinolytic resistance of healthy
      Asian subjects from Hat Yai, Songkhla, Thailand (Thai) vs. healthy North American
      subjects from Seattle, Washington, USA (SEA). Citrated plasma samples were
      obtained from healthy adult volunteers. Fibrinogen concentration was measured in
      plasma by the method of Clauss to examine for baseline differences of fibrinogen
      concentration. Samples were then standardized to 2.8 mg/ml fibrinogen using
      physiological buffer for each sample prior to fibrinolytic testing using
      rotational thromboelastometry (ROTEM) to examine for differences of clot lysis
      not attributable to fibrinogen concentration alone. Clot lysis was examined with
      ROTEM extrinsic pathway activation in the presence of 0, 0.5, and 1.0 MUg/ml of
      tissue plasminogen activator (tPA). Two-way repeated measures analysis of
      variance was used to determine the effects of tPA and study group on ROTEM
      parameters. N = 49 Thai samples were compared with N = 58 SEA samples. Mean (SD)
      fibrinogen concentration was significantly increased for the Thai group at 4.03
      (0.79) mg/ml vs. the SEA group at 3.66 (0.70) mg/ml (t test P = 0.014). After
      standardization of all samples to equivalent fibrinogen concentration, there were
      no differences in clot formation between groups without tPA. There was a
      significant effect of increasing tPA concentration on all ROTEM parameters except
      for clotting time. There were significant individual differences for amplitude at
      10 min and lysis onset time, where amplitude at 10 min was significantly
      increased and lysis onset time was significantly prolonged for Thai vs. SEA at
      tPA concentrations of 0.5 and 1.0 MUg/ml. Variability in thrombosis and
      hemostasis in Asians vs. other populations is likely to involve differences of
      fibrinogen concentration and regulation of clot lysis.

PMID- 29337701
TI  - Update on metal-induced occupational lung disease.
AB  - PURPOSE OF REVIEW: Occupational and environmental exposures to metals can result
      in multiple pulmonary conditions. This article will review recent epidemiologic
      and mechanistic studies that have enhanced our understanding of the association
      between particular lung diseases and exposure to specific metals. RECENT
      FINDINGS: Recent studies have broadened our understanding of the mechanisms of
      lung diseases such as CBD in established industries and drawn attention to
      conditions that may arise from exposure to metals such as indium in developing
      technologies. New diagnostic techniques such as elemental tissue analysis may
      help establish a diagnosis of metal-induced occupational lung disease. Electronic
      cigarette devices, environmental pollutants, and the growing use of nanoparticle
      sized metals pose additional risks to workers and consumers. SUMMARY: Recognizing
      the risks of pulmonary disease in workers exposed to metals and performing a
      thorough occupational history and diagnostic work-up in patients with unexplained
      respiratory findings is necessary to promote understanding and prevention of
      metal-induced lung disease.

PMID- 29337699
TI  - Associations Between Nurse-Guided Variables and Plasma Oxytocin Trajectories in
      Premature Infants During Initial Hospitalization.
AB  - BACKGROUND: Oxytocin (OT) is a social hormone that may help researchers
      understand how nurse-guided interventions during initial infant hospitalization,
      such as supporting human milk expression, promoting comforting touch, and
      reducing exposure to stressors, affect preterm brain development. PURPOSE: To
      determine whether factors related to human milk, touch, or stressor exposure are
      related to plasma OT trajectories in premature infants. METHODS: Plasma from 33
      premature infants, born gestational ages 25 to (Equation is included in full-text
      article.)weeks, was collected at 14 days of life and then weekly until 34 weeks'
      corrected gestational age (CGA). Variables related to feeding volumes of human
      milk and formula; touch, as indexed by skin-to-skin contact (SSC) and swaddled
      holding; and clinical stressors were extracted from the electronic medical
      record. Linear mixed-models tested associations between nurse-guided variables
      and plasma OT trajectories. RESULTS: In the final model, same-day SSC was
      positively related not only to plasma OT levels at 27 weeks' CGA (beta= .938, P =
      .002) but also to a decline in plasma OT levels over time (beta=-.177, P = .001).
      Volume of enteral feeds (mL/kg/d), its interaction with CGA, and number of
      stressful procedures were not statistically significant (beta= .011, P = .077;
      beta=-.002, P = .066; and beta= .007, P = .062, respectively). IMPLICATIONS FOR
      PRACTICE: Nurse-guided interventions are associated with infant plasma OT levels,
      suggesting nurses may impact the neurobiology of the developing premature infant.
      IMPLICATIONS FOR RESEARCH: Replication with larger sample sizes and randomized
      controlled trial designs is needed to test effects of specific nursing
      interventions on infant OT.

PMID- 29337702
TI  - Changing concepts of HIV infection and renal disease.
AB  - PURPOSE OF REVIEW: Human immunodeficiency virus (HIV)-associated nephropathy
      (HIVAN) was identified as the major renal manifestation of HIV infection early in
      the HIV epidemic. However, HIV infection now is associated with a different
      spectrum of renal lesions leading to chronic kidney disease. This review examines
      the changes in kidney injury occurring in the current HIV era and the factors
      involved in this transformation of disease expression. RECENT FINDINGS: The
      incidence of HIVAN and opportunistic infections in HIV-infected individuals has
      declined in concert with the use of effective combination antiretroviral agents.
      Chronic kidney disease has become more prevalent as patients infected with HIV
      are living longer and developing non-HIV-associated diseases such as hypertension
      and diabetes. Additionally, noncollapsing focal and segmental glomerulosclerosis,
      co-infection with hepatitis C, HIV-associated immune complex kidney disease, HIV
      related accelerated aging, and antiretroviral therapies contribute to progressive
      loss of renal function. SUMMARY: HIV infection is now associated with a variety
      of renal lesions causing chronic kidney disease, not all of which are virally
      induced. It is important to determine the cause of renal functional decline in an
      HIV-infected patient, as this will impact patient management and prognosis.

PMID- 29337703
TI  - New antibiotics for ventilator-associated pneumonia.
AB  - PURPOSE OF REVIEW: Ventilator-associated pneumonia (VAP) caused by multidrug
      resistant (MDR) bacteria represents a global emerging problem. Delayed
      prescription of an adequate treatment for VAP has been associated with higher
      morbidity and mortality. New molecules have been developed to face the need of
      compounds that are active against resistant Gram-positive and Gram-negative
      pathogens. The aim of this review is to summarize the current scenario of new
      therapeutic options for the treatment of VAP. RECENT FINDINGS: A number of new
      antibiotics with activity against MDR have been recently approved for the
      treatment of VAP, and other agents are under investigation. In this review, the
      authors summarize the current therapeutic options for the treatment of VAP that
      showed promising implications for clinical practice, including new compounds
      belonging to old antibiotic classes (e.g., ceftolozane/tazobactam,
      ceftazidime/avibactam meropenem/vaborbactam, imipenem/relebactam, tedizolid,
      cefiderocol, eravacycline, and plazomicin) and novel chemical classes, such as
      murepavadin. Nebulized antibiotics that are currently in development for the
      treatment of pneumonia in mechanically ventilated patients are also presented.
      SUMMARY: Newly approved and investigational drugs for the treatment of VAP are
      expected to offer many advantages for the management of patients with respiratory
      infections caused by MDR. Promising characteristics of new compounds include high
      activity against both methicillin-resistant Staphylococcus aureus and MDR Gram
      negative bacteria and a favorable safety profile.

PMID- 29337704
TI  - The what, when and how in performing and interpreting microbiological diagnostic
      tests in skin and soft tissue infections.
AB  - PURPOSE OF REVIEW: To summarize and classify the most recent and relevant
      microbiological studies for each type of skin and soft tissue infection (SSTI).
      RECENT FINDINGS: Following Infectious Diseases Society of America and Food and
      Drug Administration classifications of SSTIs, we differentiate between two large
      groups, the superficial or uncomplicated infections and the complicated
      infections with deep involvement. It is not usually necessary to obtain
      microbiological samples in uncomplicated infections, except in cases of
      recurrences or for epidemiological control purposes. In the case of complicated
      infections, the samples are of two different types: those obtained from the
      affected area (surgical samples, punctures of abscesses or swabs) and systemic
      samples (i.e. blood cultures). The clinical condition also determines the type of
      samples to be obtained. In cases of systemic involvement, blood cultures are
      mandatory. For immunocompromised patients, who may present atypical infections,
      detection of antigens, serologies or molecular biology techniques may be helpful.
      The rapid diagnosis is currently the goal to be pursued by implementing
      techniques such as matrix assisted laser desorption ionization-time of flight,
      commercial real-time PCR or the promising metagenomics. SUMMARY: Microbiological
      diagnosis is one of the cornerstones of the management of SSTIs. Prompt obtaining
      and processing of the necessary samples, depending on the clinical situation of
      the patient, is of relevance in the decision-making process. Rapid and fluid
      reporting of the results (identification, mechanisms of resistance and
      antibiogram) will improve the management of these patients.

PMID- 29337705
TI  - How does 'metabolic surgery' work its magic? New evidence for gut microbiota.
AB  - PURPOSE OF REVIEW: Metabolic surgery is recommended for the treatment of type 2
      diabetes for its potent ability to improve glycemic control. However, the
      mechanisms underlying the beneficial effects of metabolic surgery are still under
      investigation. We provide an updated review of recent studies into the molecular
      underpinnings of metabolic surgery, focusing in on what is known about the role
      of gut microbiota. Over the last 7 years several reports have been published on
      the topic, however the field is expanding rapidly. RECENT FINDINGS: Studies have
      now linked the regulation of glucose and lipid metabolism, neuronal and
      intestinal adaptations, and hormonal and nutrient signaling pathways to gut
      microbiota. Given that the composition of gut microbiota is altered by metabolic
      surgery, investigating the potential mechanism and outcomes of this change are
      now a priority to the field. SUMMARY: As evidence for a role for microbiota
      builds, we expect future patients may receive microbe-based therapeutics to
      improve surgical outcomes and perhaps one day preclude the need for surgical
      therapies all together. In this review and perspective, we evaluate the current
      state of the field and its future.

PMID- 29337706
TI  - Cholesterol efflux in the transplant patient.
AB  - PURPOSE OF REVIEW: Cholesterol metabolism is increasingly recognized in
      inflammatory diseases including transplantation. This review discusses the
      mechanistic underpinnings that tie macrophage cholesterol efflux capacity (CEC)
      of high-density lipoprotein (HDL) to chronic rejection in transplanted patients.
      RECENT FINDINGS: Animal studies suggest that administration of apolipoprotein A
      I, the main protein constituent of HDL, can prevent transplant arteriosclerosis.
      apoA-I administration increases CEC of HDL. In patients with cardiac allograft
      vasculopathy (CAV), decreased CEC has been associated with poorer survival. In
      addition, reduced CEC in recipients, pretransplant, has been associated with the
      development of CAV and renal allograft survival. SUMMARY: These recent findings
      raise the hypothesis that increasing cholesterol efflux may prevent chronic
      rejection and improve allograft survival after transplant. Reconstituted HDL
      significantly increases CEC and is currently in clinical development for
      traditional atherosclerosis. Clinical trials of reconstituted HDL administration
      in transplantation should be performed.

PMID- 29337707
TI  - Induction chemotherapy in acute myeloid leukaemia: origins and emerging
      directions.
AB  - PURPOSE OF REVIEW: This review summarizes the hallmark developments in induction
      chemotherapy for acute myeloid leukaemia and further describes future directions
      in its evolution. RECENT FINDINGS: We describe the origin of induction
      chemotherapy. We also describe notable modifications and adjustments to 7+3
      induction chemotherapy since its development. Finally, we describe new efforts to
      modify and add new agents to induction therapy, including '7+3 Plus'
      combinations. SUMMARY: Induction chemotherapy remains the standard of care for
      the majority of patients with acute myeloid leukaemia. However, its success is
      limited in a subset of patients by toxicity, failure to achieve remission and
      potential for subsequent relapse. Novel agents such as mutant fms like tyrosine
      kinase 3 inhibitors, mutant isocitrate dehydrogenase inhibitors, CD33-antibody
      drug conjugates and liposomal formulations have demonstrated significant
      potential as modifications to traditional induction chemotherapy.

PMID- 29337708
TI  - Using Iterative Plan-Do-Study-Act Cycles to Improve Teaching Pedagogy.
AB  - Most students entering nursing programs today are members of Generation Y or the
      Millennial generation, and they learn differently than previous generations.
      Nurse educators must consider implementing innovative teaching strategies that
      appeal to the newest generation of learners. The Plan-Do-Study-Act cycle is a
      framework that can be helpful when planning, assessing, and continually improving
      teaching pedagogy. This article describes the use of iterative Plan-Do-Study-Act
      cycles to implement a change in teaching pedagogy.

PMID- 29337709
TI  - The Relationship Between Socioeconomic Status (SES) and NCLEX-RN: Comparing SES
      Indicators in Mediated Logistic Regression.
AB  - The main purpose of this study was to examine the relationship between
      socioeconomic status (SES), ACT test scores, and the National Council Licensure
      Examination-Registered Nurse (NCLEX-RN) through a mediated logistic regression
      model. ACT is often considered one of the strongest predictors of success on the
      NCLEX-RN. Data from nursing students (N = 1,176) at a large, Midwestern
      university were analyzed. The goal was to determine if the predictive power of
      ACT on the NCLEX-RN stems from the influence of SES on ACT. A significant
      indirect effect through the causal chain of Pell Grant eligibility (i.e., SES)
      >ACT->NCLEX-RN was found.

PMID- 29337710
TI  - Analysis of First-Time Unsuccessful Attempts on the Certified Nurse Educator
      Examination.
AB  - AIM: This retrospective analysis examined first-time unsuccessful attempts on the
      Certified Nurse Educator (CNE) examination from September 2005 through September
      2011 (n = 390). BACKGROUND: There are few studies examining certification within
      the academic nurse educator role. There is also a lack of evidence to assist
      nurse educators in understanding those factors that best support success on the
      CNE exam. METHOD: Nonexperimental, descriptive, retrospective correlational
      design using chi-square test of independence and factorial analyses of variance.
      RESULTS: A statistically significant relationship was found between first-time
      failure and highest degree obtained and institutional affiliation on the CNE
      exam. There was no statistically significant effect on mean scores in any of the
      six content areas measured by the CNE exam as related to highest degree or
      institutional affiliation. CONCLUSION: The findings from this study support a
      previous recommendation for faculty development, experience in the role, and
      doctoral preparation prior to seeking certification.

PMID- 29337711
TI  - Why We Became Nurse Educators: Findings From a Nationwide Survey of Current Nurse
      Educators.
AB  - AIM: The aim of the study was to identify what a national sample of nurse faculty
      believe will help build the faculty population. BACKGROUND: The aging population
      contributes to the need for new nurses while reducing the number of experienced
      faculty. Retaining faculty and attracting younger faculty are essential. METHOD:
      This descriptive study used an online survey. Nurse educators teaching at all
      levels (n = 940) were asked to rate the effectiveness of attraction, recruitment,
      and retention strategies. This article reports on responses to one of the
      survey's open-ended question; a content analysis was conducted to develop a
      narrative description about why respondents chose nursing education. RESULTS:
      Respondents wanted to teach in a stimulating yet flexible work environment, hoped
      to influence the profession, had been influenced by educators, and sought change
      and challenge in their careers. CONCLUSION: Faculty find nursing academia
      satisfying and rewarding, but noncompetitive compensation and unsatisfactory work
      environments can eclipse satisfiers.

PMID- 29337712
TI  - Femoral Component Sizing During Total Knee Arthroplasty: Anterior Versus
      Posterior Referencing.

PMID- 29337713
TI  - Calculated versus Measured MVV-Surrogate Marker of Ventilatory CPET-Erratum.

PMID- 29337714
TI  - Greater Effect of East versus West Travel on Jet Lag, Sleep, and Team Sport
      Performance-Erratum.

PMID- 29337715
TI  - Labyrinthine Sequestrum: A Case Report and Review of the Literature.
AB  - OBJECTIVE: To report the presentation, diagnosis, management, and convalescence
      of labyrinthine sequestrum (LS) and summarize all previously published cases.
      PATIENT(S): Eleven-year-old female with LS. INTERVENTION(S): Multidisciplinary
      diagnostic evaluation and treatment. MAIN OUTCOME MEASURES: Imaging and
      laboratory findings, medical and surgical treatment. RESULTS: We describe a case
      of LS secondary to medically recalcitrant suppurative otitis media in an 11-year
      old female and review all eight previously reported cases. The index patient
      presented after 6 months of otitis media, profound unilateral hearing loss, with
      symptoms suggesting meningitis. Temporal bone CT demonstrated marked bony
      destruction of the left otic capsule. Gadolinium-enhanced MRI showed an enhancing
      process with evidence of meningitis and subdural empyema. The patient was treated
      with surgical debridement and culture directed antibiotic therapy. Posttreatment
      imaging showed resolution of intracranial infection with fibrous bony healing of
      the otic capsule resembling fibrous dysplasia. CONCLUSION: LS is a rare form of
      labyrinthitis characterized by centrifugal destruction of the otic capsule. The
      current index case highlights the importance of combined medical and surgical
      treatment and describes for the first time in the literature the fibrous
      ossification of the otic capsule following disease resolution.

PMID- 29337716
TI  - Management of Biceps Tendon Pathology: From the Glenoid to the Radial Tuberosity.
AB  - Management of proximal and distal biceps tendon pathology is evolving. The long
      head of the biceps tendon, if inflamed, may be a pain-producing structure. In
      appropriately indicated patients, a symptomatic long head of the biceps tendon
      can be surgically managed via tenotomy, tenodesis, and/or superior labrum
      anterior to posterior repair. In some patients, primary superior labrum anterior
      to posterior pathology can be managed via biceps tenodesis. Determining which
      procedure is most appropriate and which technique and implant are preferred for a
      given patient with biceps tendon pathology is controversial. Less debate exists
      with regard to the timing of distal biceps tendon repair; however, considerable
      controversy exists with regard to selection of an appropriate surgical technique
      and implant. In addition, the treatment of patients with a chronic and/or
      retracted distal biceps tendon tear and patients in whom distal biceps tendon
      repair fails is extremely challenging. Orthopaedic surgeons should understand the
      anatomy of, nonsurgical and surgical treatment options for, and outcomes of
      patients with proximal or distal biceps tendon pathology.

PMID- 29337717
TI  - Transforaminal Lumbar Interbody Fusion: Traditional Open Versus Minimally
      Invasive Techniques.
AB  - Recently, minimally invasive spine arthrodesis has gained popularity among spine
      surgeons. Minimally invasive techniques have advantages and disadvantages
      compared with traditional open techniques. Comparisons between short-term
      outcomes of minimally invasive transforaminal interbody fusion and open
      transforaminal interbody fusion in terms of estimated blood loss, postoperative
      pain, and hospital length of stay have been well documented and generally favor
      the minimally invasive technique. However, the advantages of minimally invasive
      transforaminal interbody fusion must be evaluated in the context of long-term
      results, such as patient-reported outcomes and the success of arthrodesis.
      Because the literature is equivocal in identifying the superior technique for
      successful long-term outcomes, more study is needed. Patient safety, the risk of
      complications, and the cost of these techniques also must be considered.

PMID- 29337718
TI  - Physical Inactivity from Youth to Adulthood and Risk of Impaired Glucose
      Metabolism.
AB  - INTRODUCTION: Physical activity (PA) is important in the prevention and treatment
      of impaired glucose metabolism. However, association of physical inactivity
      during the transition between childhood and adulthood with glucose metabolism is
      unknown. Therefore, we studied the association of persistent physical inactivity
      since childhood with glucose metabolism in adulthood. METHODS: Data were drawn
      from the ongoing, Cardiovascular Risk in Young Finns Study with repeated follow
      ups between 1980 and 2011 (baseline age, 3-18 yr; n = 3596). Impaired glucose
      metabolism was defined as having impaired fasting glucose (6.1-6.9 mmol.L) or
      type 2 diabetes in adulthood. Leisure-time PA habits were repeatedly collected
      with a standardized questionnaire and expressed as a PA Index. Using PA Index,
      four groups were formed (n = 2000): 1) persistently low PA, 2) decreasingly
      active, 3) increasingly active, and 4) persistently active subjects. Poisson
      regression model was used to examine the association between PA groups and
      impaired glucose metabolism. RESULTS: The proportion of the sample with impaired
      glucose metabolism was 16.1% in individuals with persistently low PA, 14.5% in
      decreasingly active, 6.8% in increasingly active, and 11.1% in persistently
      active. Compared with individuals with persistently low PA, age and sex-adjusted
      risk for impaired glucose metabolism were lower in those who increased PA
      (relative risk [RR], 0.47; 95% confidence interval [CI], 0.29-0.76) and in those
      who were persistently active (RR, 0.70; 95% CI, 0.51-0.97), but similar in those
      who decreased PA (RR, 0.93; 95% CI, 0.66-1.36). CONCLUSIONS: Persistently
      physically inactive lifestyle from youth to adulthood is associated with
      increased risk of impaired glucose metabolism in adulthood. Importantly, a
      moderate increase in PA lowered the risk. The results highlight the importance of
      avoiding physically inactive lifestyle at all stages of life.

PMID- 29337719
TI  - The effect of a hybrid training program.
AB  - Improving nursing communication skills and HCAHPS scores.

PMID- 29337720
TI  - Update on the Role of Actovegin in Musculoskeletal Medicine: A Review of the Past
      10 Years.
AB  - BACKGROUND: Actovegin is a biological drug with a controversial history of use in
      the treatment of sports injuries during the past 60 years. Particular concerns
      have been raised about its ergogenic potential to enhance performance, but some
      of these have been based on little more than anecdote. OBJECTIVES: In this
      article, we review the most recent scientific evidence to determine the clinical
      efficacy, safety profile, and legal status of Actovegin. METHODS: We considered
      all studies directly commenting on experience with Actovegin use as the primary
      intervention within the past 10 years. Outcomes included mechanisms of action,
      clinical efficacy in enhancing muscle repair, any report of safety issues, and
      any evidence for ergogenic effect. RESULTS: Our database search returned 212
      articles, abstracts were screened, and after inclusion/exclusion criteria were
      applied, 25 articles were considered: Publications included 11 primary research
      articles (7 in vitro studies and 4 clinical trials), 8 review articles, 5
      editorials, and a single case report. CONCLUSIONS: Current literature is still
      yet to define the active compound(s) of Actovegin, but suggests that it shows
      antioxidant and antiapoptotic properties, and may also upregulate macrophage
      responses central to muscle repair. Clinical efficacy was supported by one new
      original research article, and the use of Actovegin to treat muscle injuries
      remains safe and supported. Two articles argued the ergogenic effect of
      Actovegin, but in vitro findings did not to translate to the outcomes of a
      clinical trial. An adequate and meaningful scientific approach remains difficult
      in a field where there is immense pressure to deliver cutting-edge therapies.

PMID- 29337722
TI  - In Response to: Influence and Reliability of Different Correction Formulas on QTc
      Calculation.

PMID- 29337721
TI  - Continuing Play, Symptom Severity, and Symptom Duration After Concussion in Youth
      Athletes.
AB  - OBJECTIVE: To determine whether continuing to play after a concussion is
      associated with higher symptom burden or prolonged symptom duration. DESIGN:
      Patients who presented for care at a sport concussion clinic within the first 3
      weeks of injury were asked whether they continued to play immediately after their
      injury. SETTING: Sport concussion clinic within a regional tertiary care
      hospital. MAIN OUTCOME MEASURES: Clinical outcomes including symptom severity,
      symptom duration, age, time from injury-clinical presentation, sex, sport type,
      previous concussion history, and whether or not they experienced loss of
      consciousness or amnesia at the time of injury were recorded. Univariable
      comparisons between those who did and did not report continuing play were
      conducted. Multivariable linear regression models were constructed to identify
      the independent association of continuing to play postinjury with symptom burden
      and symptom recovery time, while controlling for the effect of potential
      confounding variables. RESULTS: A total of 516 patients were included in the
      study, assessed a mean of 12.1 +/- 5.2 days postinjury (35% female, mean age =
      14.5 +/- 2.3 years). A total of 227 (44%) continued play after sustaining a
      concussion. Continuing to play postconcussion was independently associated with
      higher symptom severity during the initial clinical evaluation [beta-coefficient
      = 6.144, 95% confidence interval (CI), 1.357-10.93], but not with symptom
      duration evaluation (beta-coefficient = 1.794, 95% CI, -15.66 to 19.25).
      CONCLUSION: Those who continued to play postconcussion presented with more severe
      symptoms after injury. Recognition of suspected concussion and removal from play
      on diagnosis confirmation may lead to better initial clinical outcomes after
      concussion among child and adolescent athletes.

PMID- 29337723
TI  - New Recommendations on Sport-Related Concussions: Stronger Methodology, Practical
      Messages, and Remaining Challenges.

PMID- 29337724
TI  - Statistical Significance Versus Clinical Importance of Observed Effect Sizes:
      What Do P Values and Confidence Intervals Really Represent?
AB  - Effect size measures are used to quantify treatment effects or associations
      between variables. Such measures, of which >70 have been described in the
      literature, include unstandardized and standardized differences in means, risk
      differences, risk ratios, odds ratios, or correlations. While null hypothesis
      significance testing is the predominant approach to statistical inference on
      effect sizes, results of such tests are often misinterpreted, provide no
      information on the magnitude of the estimate, and tell us nothing about the
      clinically importance of an effect. Hence, researchers should not merely focus on
      statistical significance but should also report the observed effect size.
      However, all samples are to some degree affected by randomness, such that there
      is a certain uncertainty on how well the observed effect size represents the
      actual magnitude and direction of the effect in the population. Therefore, point
      estimates of effect sizes should be accompanied by the entire range of plausible
      values to quantify this uncertainty. This facilitates assessment of how large or
      small the observed effect could actually be in the population of interest, and
      hence how clinically important it could be. This tutorial reviews different
      effect size measures and describes how confidence intervals can be used to
      address not only the statistical significance but also the clinical significance
      of the observed effect or association. Moreover, we discuss what P values
      actually represent, and how they provide supplemental information about the
      significant versus nonsignificant dichotomy. This tutorial intentionally focuses
      on an intuitive explanation of concepts and interpretation of results, rather
      than on the underlying mathematical theory or concepts.

PMID- 29337725
TI  - In Response.

PMID- 29337726
TI  - Valveless Trocar Systems and Respiratory Mechanics: Need for Revaluation.

PMID- 29337727
TI  - Ultrasound in Anesthesia, Critical Care, and Pain Management: A Critic's Review.

PMID- 29337728
TI  - Continuous Pulse Oximetry Does Not Measure Blood Pressure.

PMID- 29337729
TI  - Evaluation of Almitrine Infusion During Veno-Venous Extracorporeal Membrane
      Oxygenation for Severe Acute Respiratory Distress Syndrome in Adults.
AB  - This single-center case series investigated the effect of almitrine infusion on
      PaO2/fraction of inspired oxygen (FIO2) in 25 patients on veno-venous
      extracorporeal membrane oxygenation for severe acute respiratory distress
      syndrome. A positive trial was defined as an increase of PaO2/FIO2 ratio >=20%.
      Thirty-two trials were performed. Twenty (62.5%, 95% confidence interval, 37.5%
      75%) trials in 18 patients were positive, with a median PaO2/FIO2 ratio increase
      of 35% (25%-43%). A focal acute respiratory distress syndrome and inhaled nitric
      oxide therapy were more frequent in patients with a positive response to
      almitrine. We observed no complications of almitrine use.

PMID- 29337730
TI  - Effects of Electrical Transcutaneous Vagus Nerve Stimulation on the Perceived
      Intensity of Repetitive Painful Heat Stimuli: A Blinded Placebo- and Sham
      Controlled Randomized Crossover Investigation.
AB  - BACKGROUND: Transcutaneous vagus nerve stimulation (TVNS) is a promising
      treatment for acute and chronic pain. However, experimental studies yielded
      controversial results. We examined if TVNS reduces the perceived intensity of
      repetitive painful heat stimulation and temporal summation of pain (TSP) in
      healthy volunteers in comparison with placebo and sham stimulation, as well as no
      intervention. METHODS: In 4 sessions, 90 heat pulse stimuli at individual pain
      tolerance temperature were applied to the ventral forearm of 49 healthy
      volunteers (25 women) using a Contact Heat Evoked Potential Stimulator thermode
      (Medoc, Ramat Yishai, Israel). Pain intensity was assessed with verbal ratings on
      a numeric pain scale (0-100) at every tenth heat pulse. After the first session
      in which pain intensities without intervention were evaluated, participants
      completed 3 sessions in a single-blinded randomized crossover manner: (1) sham
      stimulation applied at the earlobes, (2) placebo stimulation (inactive device),
      or (3) TVNS applied at the cymbas conchae. Primary data were analyzed using
      analysis of variance for repeated measures and t test for paired samples.
      RESULTS: Pain intensity decreased during all interventions as compared to no
      intervention (etap = 0.22, P < .001; mean difference TVNS versus no intervention
      9.5; 95% confidence interval [CI], 3.6-15.4; P < .001). Hypoalgesic effect of
      TVNS was better than that of placebo and sham in men before the onset of TSP
      (mean differences for TVNS versus placebo 6.2; 95% CI, 0.2-12.1; TVNS versus sham
      6.2; 95% CI, 0.2-12.1; P < .05). In women, TSP response under TVNS was decreased
      if compared to no intervention (median difference, 7.5; 95% CI, 3.5-15.0; P =
      .003). CONCLUSIONS: TVNS, placebo, and sham stimulation exerted comparable
      effects under experimental heat pain stimulation. Only in male participants, TVNS
      was superior to sham and placebo conditions in the reduction of heat pain before
      the onset of TSP.

PMID- 29337731
TI  - In Response.

PMID- 29337738
TI  - Decision Support Alerts: Importance of Validation.

PMID- 29337740
TI  - Risk Prediction Tools: The Need for Greater Transparency.

PMID- 29337741
TI  - Regulatory Landscape for Clinical Decision Support Technology.

PMID- 29337743
TI  - Impact of a Novel Multiparameter Decision Support System on Intraoperative
      Processes of Care and Postoperative Outcomes.
AB  - BACKGROUND: The authors hypothesized that a multiparameter intraoperative
      decision support system with real-time visualizations may improve processes of
      care and outcomes. METHODS: Electronic health record data were retrospectively
      compared over a 6-yr period across three groups: experimental cases, in which the
      decision support system was used for 75% or more of the case at sole discretion
      of the providers; parallel controls (system used 74% or less); and historical
      controls before system implementation. Inclusion criteria were adults under
      general anesthesia, advanced medical disease, case duration of 60 min or longer,
      and length of stay of two days or more. The process measures were avoidance of
      intraoperative hypotension, ventilator tidal volume greater than 10 ml/kg, and
      crystalloid administration (ml . kg . h). The secondary outcome measures were
      myocardial injury, acute kidney injury, mortality, length of hospital stay, and
      encounter charges. RESULTS: A total of 26,769 patients were evaluated: 7,954
      experimental cases, 10,933 parallel controls, and 7,882 historical controls.
      Comparing experimental cases to parallel controls with propensity score
      adjustment, the data demonstrated the following medians, interquartile ranges,
      and effect sizes: hypotension 1 (0 to 5) versus 1 (0 to 5) min, P < 0.001, beta =
      -0.19; crystalloid administration 5.88 ml . kg . h (4.18 to 8.18) versus 6.17
      (4.32 to 8.79), P < 0.001, beta = -0.03; tidal volume greater than 10 ml/kg 28%
      versus 37%, P < 0.001, adjusted odds ratio 0.65 (0.53 to 0.80); encounter charges
      $65,770 ($41,237 to $123,869) versus $69,373 ($42,101 to $132,817), P < 0.001,
      beta = -0.003. The secondary clinical outcome measures were not significantly
      affected. CONCLUSIONS: The use of an intraoperative decision support system was
      associated with improved process measures, but not postoperative clinical
      outcomes.

PMID- 29337744
TI  - Defining the Intrinsic Cardiac Risks of Operations to Improve Preoperative
      Cardiac Risk Assessments.
AB  - BACKGROUND: Current preoperative cardiac risk stratification practices group
      operations into broad categories, which might inadequately consider the intrinsic
      cardiac risks of individual operations. We sought to define the intrinsic cardiac
      risks of individual operations and to demonstrate how grouping operations might
      lead to imprecise estimates of perioperative cardiac risk. METHODS: Elective
      operations (based on Common Procedural Terminology codes) performed from January
      1, 2010 to December 31, 2015 at hospitals participating in the American College
      of Surgeons National Surgical Quality Improvement Program were studied. A
      composite measure of perioperative adverse cardiac events was defined as either
      cardiac arrest requiring cardiopulmonary resuscitation or acute myocardial
      infarction. Operations' intrinsic cardiac risks were derived from mixed-effects
      models while controlling for patient mix. Resultant risks were sorted into low-,
      intermediate-, and high-risk categories, and the most commonly performed
      operations within each category were identified. Intrinsic operative risks were
      also examined using a representative grouping of operations to portray within
      group variation. RESULTS: Sixty-six low, 30 intermediate, and 106 high intrinsic
      cardiac risk operations were identified. Excisional breast biopsy had the lowest
      intrinsic cardiac risk (overall rate, 0.01%; odds ratio, 0.11; 95% CI, 0.02 to
      0.25) relative to the average, whereas aorto-bifemoral bypass grafting had the
      highest (overall rate, 4.1%; odds ratio, 6.61; 95% CI, 5.54 to 7.90). There was
      wide variation in the intrinsic cardiac risks of operations within the
      representative grouping (median odds ratio, 1.40; interquartile range, 0.88 to
      2.17). CONCLUSIONS: A continuum of intrinsic cardiac risk exists among
      operations. Grouping operations into broad categories inadequately accounts for
      the intrinsic cardiac risk of individual operations.

PMID- 29337748
TI  - Avoidance of Hyperoxemia during Cardiopulmonary Bypass: Why Does Pathophysiology
      Not Always Translate into Clinical Outcome?

PMID- 29337749
TI  - Clinical Technology and Glucose Management.

PMID- 29337750
TI  - In Reply.

PMID- 29337751
TI  - Perioperative Pain Management for Total Knee Arthroplasty: Need More Focus on the
      Forest and Less on the Trees.

PMID- 29337752
TI  - In Reply.

PMID- 29337753
TI  - Solvent Matters!

PMID- 29337754
TI  - In Reply.

PMID- 29337755
TI  - Distal Subclavian Cannulation and Extravasation.

PMID- 29337756
TI  - Taller People Should Have as Their Normal a Higher Body Mass Index.

PMID- 29337757
TI  - Unusual Catheter Placement on Chest Radiograph: Two Dimensions, Two Possible
      Locations (or More).

PMID- 29337758
TI  - In Reply.

PMID- 29337761
TI  - Children's Recognition of Emotional Prosody in Spectrally Degraded Speech Is
      Predicted by Their Age and Cognitive Status.
AB  - OBJECTIVES: It is known that school-aged children with cochlear implants show
      deficits in voice emotion recognition relative to normal-hearing peers. Little,
      however, is known about normal-hearing children's processing of emotional cues in
      cochlear implant-simulated, spectrally degraded speech. The objective of this
      study was to investigate school-aged, normal-hearing children's recognition of
      voice emotion, and the degree to which their performance could be predicted by
      their age, vocabulary, and cognitive factors such as nonverbal intelligence and
      executive function. DESIGN: Normal-hearing children (6-19 years old) and young
      adults were tested on a voice emotion recognition task under three different
      conditions of spectral degradation using cochlear implant simulations (full
      spectrum, 16-channel, and 8-channel noise-vocoded speech). Measures of
      vocabulary, nonverbal intelligence, and executive function were obtained as well.
      RESULTS: Adults outperformed children on all tasks, and a strong developmental
      effect was observed. The children's age, the degree of spectral resolution, and
      nonverbal intelligence were predictors of performance, but vocabulary and
      executive functions were not, and no interactions were observed between age and
      spectral resolution. CONCLUSIONS: These results indicate that cognitive function
      and age play important roles in children's ability to process emotional prosody
      in spectrally degraded speech. The lack of an interaction between the degree of
      spectral resolution and children's age further suggests that younger and older
      children may benefit similarly from improvements in spectral resolution. The
      findings imply that younger and older children with cochlear implants may benefit
      similarly from technical advances that improve spectral resolution.

PMID- 29337760
TI  - Using Thresholds in Noise to Identify Hidden Hearing Loss in Humans.
AB  - OBJECTIVES: Recent animal studies suggest that noise-induced synaptopathy may
      underlie a phenomenon that has been labeled hidden hearing loss (HHL). Noise
      exposure preferentially damages low spontaneous-rate auditory nerve fibers, which
      are involved in the processing of moderate- to high-level sounds and are more
      resistant to masking by background noise. Therefore, the effect of synaptopathy
      may be more evident in suprathreshold measures of auditory function, especially
      in the presence of background noise. The purpose of this study was to develop a
      statistical model for estimating HHL in humans using thresholds in noise as the
      outcome variable and measures that reflect the integrity of sites along the
      auditory pathway as explanatory variables. Our working hypothesis is that HHL is
      evident in the portion of the variance observed in thresholds in noise that is
      not dependent on thresholds in quiet, because this residual variance retains
      statistical dependence on other measures of suprathreshold function. DESIGN:
      Study participants included 13 adults with normal hearing (<=15 dB HL) and 20
      adults with normal hearing at 1 kHz and sensorineural hearing loss at 4 kHz (>15
      dB HL). Thresholds in noise were measured, and the residual of the correlation
      between thresholds in noise and thresholds in quiet, which we refer to as
      thresholds-in-noise residual, was used as the outcome measure for the model.
      Explanatory measures were as follows: (1) auditory brainstem response (ABR) waves
      I and V amplitudes; (2) electrocochleographic action potential and summating
      potential amplitudes; (3) distortion product otoacoustic emissions level; and (4)
      categorical loudness scaling. All measurements were made at two frequencies (1
      and 4 kHz). ABR and electrocochleographic measurements were made at 80 and 100 dB
      peak equivalent sound pressure level, while wider ranges of levels were tested
      during distortion product otoacoustic emission and categorical loudness scaling
      measurements. A model relating the thresholds-in-noise residual and the
      explanatory measures was created using multiple linear regression analysis.
      RESULTS: Predictions of thresholds-in-noise residual using the model accounted
      for 61% (p < 0.01) and 48% (p < 0.01) of the variance in the measured thresholds
      in-noise residual at 1 and 4 kHz, respectively. CONCLUSIONS: Measures of
      thresholds in noise, the summating potential to action potential ratio, and ABR
      waves I and V amplitudes may be useful for the prediction of HHL in humans. With
      further development, our approach of quantifying HHL by the variance that remains
      in suprathreshold measures of auditory function after removing the variance due
      to thresholds in quiet, together with our statistical modeling, may provide a
      quantifiable and verifiable estimate of HHL in humans with normal hearing and
      with hearing loss. The current results are consistent with the view that inner
      hair cell and auditory nerve pathology may underlie suprathreshold auditory
      performance.

PMID- 29337762
TI  - Tinnitus and Auditory Perception After a History of Noise Exposure: Relationship
      to Auditory Brainstem Response Measures.
AB  - OBJECTIVES: To determine whether auditory brainstem response (ABR) wave I
      amplitude is associated with measures of auditory perception in young people with
      normal distortion product otoacoustic emissions (DPOAEs) and varying levels of
      noise exposure history. DESIGN: Tinnitus, loudness tolerance, and speech
      perception ability were measured in 31 young military Veterans and 43 non
      Veterans (19 to 35 years of age) with normal pure-tone thresholds and DPOAEs.
      Speech perception was evaluated in quiet using Northwestern University Auditory
      Test (NU-6) word lists and in background noise using the words in noise (WIN)
      test. Loudness discomfort levels were measured using 1-, 3-, 4-, and 6-kHz pulsed
      pure tones. DPOAEs and ABRs were collected in each participant to assess outer
      hair cell and auditory nerve function. RESULTS: The probability of reporting
      tinnitus in this sample increased by a factor of 2.0 per 0.1 uV decrease in ABR
      wave I amplitude (95% Bayesian confidence interval, 1.1 to 5.0) for males and by
      a factor of 2.2 (95% confidence interval, 1.0 to 6.4) for females after adjusting
      for sex and DPOAE levels. Similar results were obtained in an alternate model
      adjusted for pure-tone thresholds in addition to sex and DPOAE levels. No
      apparent relationship was found between wave I amplitude and either loudness
      tolerance or speech perception in quiet or noise. CONCLUSIONS: Reduced ABR wave I
      amplitude was associated with an increased risk of tinnitus, even after adjusting
      for DPOAEs and sex. In contrast, wave III and V amplitudes had little effect on
      tinnitus risk. This suggests that changes in peripheral input at the level of the
      inner hair cell or auditory nerve may lead to increases in central gain that give
      rise to the perception of tinnitus. Although the extent of synaptopathy in the
      study participants cannot be measured directly, these findings are consistent
      with the prediction that tinnitus may be a perceptual consequence of cochlear
      synaptopathy.

PMID- 29337764
TI  - A National Accreditation Program for Rectal Cancer: A Long and Winding Road.

PMID- 29337765
TI  - Digestive Tract Damage: A Predictor of Early Surgical Intervention in Patients
      With Newly Diagnosed Crohn's Disease.

PMID- 29337763
TI  - The Effect of Simulated Interaural Frequency Mismatch on Speech Understanding and
      Spatial Release From Masking.
AB  - OBJECTIVE: The binaural-hearing system interaurally compares inputs, which
      underlies the ability to localize sound sources and to better understand speech
      in complex acoustic environments. Cochlear implants (CIs) are provided in both
      ears to increase binaural-hearing benefits; however, bilateral CI users continue
      to struggle with understanding speech in the presence of interfering sounds and
      do not achieve the same level of spatial release from masking (SRM) as normal
      hearing listeners. One reason for diminished SRM in CI users could be that the
      electrode arrays are inserted at different depths in each ear, which would cause
      an interaural frequency mismatch. Because interaural frequency mismatch
      diminishes the salience of interaural differences for relatively simple stimuli,
      it may also diminish binaural benefits for spectral-temporally complex stimuli
      like speech. This study evaluated the effect of simulated frequency-to-place
      mismatch on speech understanding and SRM. DESIGN: Eleven normal-hearing listeners
      were tested on a speech understanding task. There was a female target talker who
      spoke five-word sentences from a closed set of words. There were two interfering
      male talkers who spoke unrelated sentences. Nonindividualized head-related
      transfer functions were used to simulate a virtual auditory space. The target was
      presented from the front (0 degrees ), and the interfering speech was either
      presented from the front (colocated) or from 90 degrees  to the right (spatially
      separated). Stimuli were then processed by an eight-channel vocoder with tonal
      carriers to simulate aspects of listening through a CI. Frequency-to-place
      mismatch ("shift") was introduced by increasing the center frequency of the
      synthesis filters compared with the corresponding analysis filters. Speech
      understanding was measured for different shifts (0, 3, 4.5, and 6 mm) and target
      to-masker ratios (TMRs: +10 to -10 dB). SRM was calculated as the difference in
      the percentage of correct words for the colocated and separated conditions. Two
      types of shifts were tested: (1) bilateral shifts that had the same frequency-to
      place mismatch in both ears, but no interaural frequency mismatch, and (2)
      unilateral shifts that produced an interaural frequency mismatch. RESULTS: For
      the bilateral shift conditions, speech understanding decreased with increasing
      shift and with decreasing TMR, for both colocated and separate conditions. There
      was, however, no interaction between shift and spatial configuration; in other
      words, SRM was not affected by shift. For the unilateral shift conditions, speech
      understanding decreased with increasing interaural mismatch and with decreasing
      TMR for both the colocated and spatially separated conditions. Critically, there
      was a significant interaction between the amount of shift and spatial
      configuration; in other words, SRM decreased for increasing interaural mismatch.
      CONCLUSIONS: A frequency-to-place mismatch in one or both ears resulted in
      decreased speech understanding. SRM, however, was only affected in conditions
      with unilateral shifts and interaural frequency mismatch. Therefore, matching
      frequency information between the ears provides listeners with larger binaural
      hearing benefits, for example, improved speech understanding in the presence of
      interfering talkers. A clinical procedure to reduce interaural frequency mismatch
      when programming bilateral CIs may improve benefits in speech segregation that
      are due to binaural-hearing abilities.

PMID- 29337766
TI  - Worrying About Postoperative Functional Outcomes in Young Women With Colorectal
      Endometriosis: That's It!

PMID- 29337767
TI  - Presacral (Retrorectal) Tumors: Optimizing the Management Strategy.

PMID- 29337768
TI  - Expert Commentary on Presacral Tumors.

PMID- 29337769
TI  - Morbidity Following Coloanal Anastomosis: A Comparison of Colonic J-Pouch vs
      Straight Anastomosis.
AB  - BACKGROUND: Low rectal tumors are often treated with sphincter-preserving
      resection followed by coloanal anastomosis. OBJECTIVE: The purpose of this study
      was to compare the short-term complications following straight coloanal
      anastomosis vs colonic J-pouch anal anastomosis. DESIGN: Patients were identified
      who underwent proctectomy for rectal neoplasia followed by coloanal anastomosis
      in the 2008 to 2013 American College of Surgeons National Surgical Quality
      Improvement Program database. Demographic characteristics and 30-day
      postoperative complications were compared between groups. SETTINGS: A national
      sample was extracted from the American College of Surgeons National Surgical
      Quality Improvement Project database. PATIENTS: Inpatients following proctectomy
      and coloanal anastomosis for rectal cancer were selected. MAIN OUTCOME MEASURES:
      Demographic characteristics and 30-day postoperative complications were compared
      between the 2 groups. RESULTS: One thousand three hundred seventy patients were
      included, 624 in the straight anastomosis group and 746 in the colonic J-pouch
      group. Preoperative characteristics were similar between groups, with the
      exception of preoperative radiation therapy (straight anastomosis 35% vs colonic
      J-pouch 48%, p = 0.0004). Univariate analysis demonstrated that deep surgical
      site infection (3.7% vs 1.4%, p = 0.01), septic shock (2.25% vs 0.8%, p = 0.04),
      and return to the operating room (8.8% vs 5.0%, p = 0.0006) were more frequent in
      the straight anastomosis group vs the colonic J-pouch group. Major complications
      were also higher (23% vs 14%, p = 0.0001) and length of stay was longer in the
      straight anastomosis group vs the colonic J-pouch group (8.9 days vs 8.1 days, p
      = 0.02). After adjusting for covariates, major complications were less following
      colonic J-pouch vs straight anastomosis (OR, 0.57; CI, 0.38-0.84; p = 0.005).
      Subgroup analysis of patients who received preoperative radiation therapy
      demonstrated no difference in major complications between groups. LIMITATIONS:
      This study had those limitations inherent to a retrospective study using an
      inpatient database. CONCLUSION: Postoperative complications were less following
      colonic J-pouch anastomosis vs straight anastomosis. Patients who received
      preoperative radiation had similar rates of complications, regardless of the
      reconstructive technique used following low anterior resection. See Video
      Abstract at http://links.lww.com/DCR/A468.

PMID- 29337770
TI  - Survival Benefit of Japanese Extended Lymphadenectomy for Clinically Node
      Negative and Node-Positive Colorectal Cancers.
AB  - BACKGROUND: The impact of extended lymphadenectomy for colorectal cancer is still
      not sufficiently clear. OBJECTIVE: The aim of the present study was to evaluate
      the survival benefit of extended lymphadenectomy compared with nonextended
      lymphadenectomy for clinically node-negative and node-positive colorectal
      cancers. DESIGN: The present study was a retrospective cohort study that used
      prospectively collected data and a propensity score matching method. SETTINGS:
      The present study was conducted at a single specialized colorectal surgery
      department. PATIENTS: Of the 1314 patients who underwent radical resection with
      nonextended or extended lymphadenectomy between 1988 and 2007, we included 711
      and 603 patients in the cN0 and cN1/2 series. Propensity score matching was
      applied, and 141 and 63 pairs were extracted from the cN0 and cN1/2 series. MAIN
      OUTCOME MEASURES: Disease-free survival, cancer-specific survival, and overall
      survival of the 2 groups were calculated and compared. RESULTS: In the cN0
      series, no differences were observed in the long-term outcomes between the
      nonextended and extended groups. In the cN1/2 series, the disease-free survival,
      cancer-specific survival and overall survival were significantly higher (log
      rank, p = 0.04, p = 0.02, and p = 0.01, respectively), and the frequency of local
      recurrence was significantly lower (p = 0.04) in the extended group. LIMITATIONS:
      The present study was limited by its nonrandomized retrospective design.
      CONCLUSIONS: Extended lymphadenectomy demonstrated a good inhibitory effect on
      the local recurrence rate and led to improved disease-free survival, cancer
      specific survival, and overall survival of patients in the cN1/2 series. See
      Video Abstract at http://links.lww.com/DCR/A517.

PMID- 29337771
TI  - Outcomes of Closed Versus Open Defects After Local Excision of Rectal Neoplasms:
      A Multi-institutional Matched Analysis.
AB  - BACKGROUND: The management of the rectal wall defect after local excision of
      rectal neoplasms remains controversial, and the existing data are equivocal.
      OBJECTIVE: This study aimed to determine the effect of open versus closed defects
      on postoperative outcomes after local excision of rectal neoplasms. DESIGN: Data
      from 3 institutions were analyzed. Propensity score matching was performed in one
      to-one fashion to create a balanced cohort comparing open and closed defects.
      SETTINGS: This study was conducted at high-volume specialist referral hospitals.
      PATIENTS: Adult patients undergoing local excision via transanal endoscopic
      surgery from 2004 to 2016 were included. Patients were assigned to open- and
      closed-defect groups, and further stratified by full- or partial-thickness
      excision. INTERVENTION: Closure of the rectal wall defect was performed at the
      surgeon's discretion. MAIN OUTCOME MEASURES: The primary outcome measured was the
      incidence of 30-day complications. RESULTS: A total of 991 patients were eligible
      (593 full-thickness excision with 114 open and 479 closed, and 398 partial
      thickness excision with 263 open and 135 closed). After matching, balanced
      cohorts consisting of 220 patients with full-thickness excision and 210 patients
      with partial-thickness excision were created. Operative time was similar for open
      and closed defects for both full-and partial-thickness excision. The incidence of
      30-day complications was similar for open and closed defects after full- (15% vs.
      12%, p = 0.432) and partial-thickness excision (7% vs 5%, p = 0.552). The total
      number of complications was also similar after full- or partial-thickness
      excision. Patients undergoing full-thickness excision with open defects had a
      higher incidence of clinically significant bleeding complications (9% vs 3%, p =
      0.045). LIMITATIONS: Data were obtained from 3 institutions with different
      equipment and perioperative management over a long time period. CONCLUSIONS:
      There was no difference in overall complications between open and closed defects
      for patients undergoing local excision of rectal neoplasms, but there may be more
      bleeding complications in open defects after full-thickness excision. A selective
      approach to defect closure may be appropriate. See Video Abstract at
      http://links.lww.com/DCR/A470.

PMID- 29337772
TI  - Salvage Surgery for Locoregional Failure in Anal Squamous Cell Carcinoma.
AB  - BACKGROUND: Anal squamous cell carcinoma is a rare cancer with a high cure rate,
      making research into the treatment of locoregional failure difficult. OBJECTIVE:
      The purpose of this study was to examine factors related to local treatment
      failure and determine the outcomes of patients undergoing local salvage
      resection. DESIGN: This was a retrospective cohort study. SETTING: This study was
      conducted at a quaternary referral center. PATIENTS: Patients with anal squamous
      cell carcinoma treated with chemoradiotherapy between January 1983 and December
      2015 were included. MAIN OUTCOME MEASURES: The influence of patient-, tumor-, and
      treatment-related factors on the primary outcome measures of locoregional
      failure, overall survival, and disease-free survival were investigated. RESULTS:
      Of 467 patients with anal squamous cell carcinoma, 63 experienced locoregional
      failure with 41 undergoing salvage resection. Twenty-seven patients (38%) had
      persistent disease and 36 (62%) developed locoregional recurrence. Multivariate
      analysis identified tumor stage (HR, 3.16; p < 0.002) as an independent predictor
      of locoregional failure. Thirty abdominoperineal resections and 11 pelvic
      exenterations were undertaken with no surgical mortality. At a median follow-up
      of 20 months (range, 4-150 months), 5-year overall and disease-free survival for
      the salvage cohort was 51% and 47%. Margin positivity was an independent
      predictor for relapse post-salvage surgery on multivariate analysis (HR, 20.1; p
      = 0.027). Nineteen patients (48%) developed further relapse, which included all
      10 patients with a positive resection margin, 3 of whom underwent re-resection.
      Of the 19 patients with relapse, 3 remain alive and 2 have persistent disease.
      LIMITATIONS: Limitations include the retrospective nature of the database, the
      prolonged time period of the study, and episodes of incomplete data. CONCLUSIONS:
      Advanced T stage is an independent predictor of local failure in anal squamous
      cell carcinoma. Most patients can be salvaged, with a positive resection margin
      being a strong predictor of further relapse and poor outcome. See Video Abstract
      at http://links.lww.com/DCR/A515.

PMID- 29337773
TI  - Prognostic Factors for Locoregional Recurrence in Neuroendocrine Tumors of the
      Rectum.
AB  - BACKGROUND: Optimal management of rectal neuroendocrine tumors is not yet well
      defined. Various pathologic factors, particularly tumor size, have been proposed
      as prognostic markers. OBJECTIVE: We characterized sequential patients diagnosed
      with rectal neuroendocrine tumors in a population-based setting to determine
      whether tumor size and other pathologic markers could be useful in guiding
      locoregional management. DESIGN: This study is a retrospective analysis of data
      from the British Columbia provincial cancer registry. SETTINGS: The study was
      conducted at a tertiary care center. PATIENTS: Sequential patients diagnosed with
      rectal neuroendocrine tumors between 1999 and 2011 were identified.
      Neuroendocrine tumors were classified as G1 and G2 tumors with a Ki-67 <=20%
      and/or mitotic count <=20 per high-power field. MAIN OUTCOME MEASURES: Baseline
      clinicopathologic data including TNM staging, depth of invasion, tumor size,
      treatment modalities, and outcomes including survival data were measured.
      RESULTS: Of 91 rectal neuroendocrine tumors, the median patient age was 58 years,
      and 35 were men. Median tumor size was 6 mm. Median length of follow-up was 58.1
      months, with 3 patients presenting with stage IV disease. Treatment included
      local ablation (n = 5), local excision (n = 79), surgical resection (n = 4), and
      pelvic radiation (n = 1; T3N1 tumor). Final margin status was positive in 17
      cases. Local relapse occurred in 8 cases and 1 relapse to bone 13 months after
      T3N1 tumor resection. Univariate analysis demonstrated an association between
      local relapse and Ki-67, mitotic count, grade, and lymphovascular invasion (p <
      0.01). Larger tumor size was associated with decreased disease-free survival.
      LIMITATIONS: Sample size was 91 patients in the whole provincial population over
      a 13-year time period because of the low incidence of rectal neuroendocrine
      tumors. CONCLUSIONS: In this population-based cohort, rectal neuroendocrine
      tumors generally presented with small, early tumors and were treated with local
      excision or surgical resection without pelvic radiation. Pathologic markers play
      a role in risk stratification and prognostication. See Video Abstract at
      http://links.lww.com/DCR/A514.

PMID- 29337775
TI  - Comparisons of Rigid Proctoscopy, Flexible Colonoscopy, and Digital Rectal
      Examination for Determining the Localization of Rectal Cancers.
AB  - BACKGROUND: Rigid proctoscopy is considered essential for rectal tumor
      localization, although the current gold standard for detection of colorectal
      cancers is colonoscopy. The European Society for Medical Oncology Guidelines
      indicate that rigid and flexible endoscopies afford essentially identical
      results, although little evidence is yet available to support this. OBJECTIVE:
      The purpose of this study was to determine the accuracy of colonoscopy in
      identifying the location of rectal cancer and to compare the results with those
      of rigid proctoscopy and digital rectal examination. DESIGN: This was a
      retrospective analysis of a prospective database. SETTINGS: The study was
      conducted at a single tertiary colorectal surgery referral center. PATIENTS: A
      total of 173 patients scheduled for curative surgery for histologically verified
      rectal adenocarcinoma between December 2009 and February 2015 were entered into
      the study, after having given informed consent. MAIN OUTCOME MEASURES: The main
      study measure was the mean difference and limits of agreement in assessment of
      the height of the distal edge of rectal cancer from the anal verge, using the
      Bland and Altman method. RESULTS: The mean difference between rigid proctoscopy
      and flexible colonoscopy was -0.2 cm (95% CI, -2.0 to 1.6 cm). The mean
      difference between rigid proctoscopy and digital rectal examination was 0.3 cm
      (95% CI, 1.9 to 2.4 cm). Intermethod variability larger than the 95% CI between
      rigid and flexible endoscopes was correlated to the tumor height (OR, 4.27 (95%
      CI, 1.84-3.10); p = 0.021). LIMITATIONS: This study was conducted in a single
      center. CONCLUSIONS: The limits of agreement (-2.0 and 1.6 cm) in identifying the
      height of rectal cancers from the anal verge are sufficiently small to support
      the view that flexible colonoscopy provides similar tumor locations to those
      measured by rigid proctoscopy, although the discrepancy occasionally exceeded 2
      cm for tumors >5 cm above the anal verge. See Video Abstract at
      http://links.lww.com/DCR/A405.

PMID- 29337774
TI  - Gadolinium-Based Contrast Agent During Pelvic MRI: Contribution to Patient
      Management in Rectal Cancer.
AB  - BACKGROUND: Few publications exist regarding gadolinium-enhanced sequences in
      rectal MRI. None have evaluated its potential impact on patient management.
      OBJECTIVE: This study aimed to assess whether gadolinium-enhanced sequences,
      including dynamic contrast enhancement, change radiologic interpretation and
      clinical management of rectal cancer. DESIGN: This is a retrospective analysis of
      100 rectal MRIs (50 baseline and 50 postneoadjuvant treatment), both without and
      with gadolinium-enhanced sequences. Treatment plans were rendered based on each
      radiologic interpretation for each case by a single experienced surgeon.
      Differences in radiologic interpretation and management were statistically
      analyzed. SETTINGS: The study was conducted at the Memorial Sloan Kettering
      Cancer Center. PATIENTS: Patients undergoing rectal MRI between 2011 and 2015 for
      baseline tumor staging and/or postneoadjuvant restaging were included. MAIN
      OUTCOME MEASURES: Primary outcome measures were changes in radiologic tumor
      stage, tumor margins, and surgical planning with the use of gadolinium at
      baseline and postneoadjuvant time points. RESULTS: At baseline, tumor downstaging
      occurred in 8 (16%) of 50 and upstaging in 4 (8%) of 50 with gadolinium.
      Postneoadjuvant treatment, upstaging occurred in 1 (2%) of 50 from T2 to T3a. At
      baseline, mean distances from tumor to anorectal ring, anal verge, and mesorectal
      fascia were not statistically different with gadolinium. However, in 7 patients,
      differences could have resulted in treatment changes, accounted for by changes in
      relationships to anterior peritoneal reflection (n = 4), anorectal ring (n = 2),
      or anal verge (n = 1). Postneoadjuvant treatment, distances to anorectal ring and
      anal verge (in centimeters) were statistically smaller with gadolinium (p =
      0.0017 and p = 0.0151) but could not have resulted in clinically significant
      treatment changes. LIMITATIONS: This study was limited by its retrospective
      design. CONCLUSIONS: The use of gadolinium at baseline MRI could have altered
      treatment in 24% of patients because of differences in tumor stage or position.
      Postneoadjuvant treatment, gadolinium resulted in statistically smaller distances
      to sphincters, which could influence surgical decision for sphincter-preserving
      rectal resection. See Video Abstract at http://links.lww.com/DCR/A444.

PMID- 29337776
TI  - Lemann Index at Diagnosis Predicts the Risk of Early Surgery in Crohn's Disease.
AB  - BACKGROUND: Identifying patients with Crohn's disease with rapid disease progress
      or high risk of early surgery is crucial to clinical decision making. OBJECTIVE:
      The aim was to evaluate the correlation between the Lemann index at diagnosis and
      abdominal surgery in the first year after Crohn's disease diagnosis and to find
      the risk factors for early surgery. DESIGN: This was a retrospective cohort
      study. SETTINGS: The study was conducted at a single tertiary hospital. PATIENTS:
      Patients diagnosed with Crohn's disease between 2013 and 2015 in our center were
      included. MAIN OUTCOME MEASURES: The outcome of interest was the need for an
      abdominal surgery within 1 year after the Lemann index evaluation at diagnosis.
      RESULTS: Of 212 eligible patients, 48 patients underwent abdominal surgery during
      follow-up. Lemann index was much higher in the surgery group (5.3 vs 2.6; p <
      0.001). On tertiles of the Lemann index, the frequency of surgery grew (2.8%,
      9.9%, and 55.7%; p < 0.001) as the Lemann index increased. The receiver operating
      characteristic curve was constructed taking into account the Lemann index for
      selecting patients with a high risk of surgery. Specificity, sensitivity, and
      area under receiver operating characteristic curve were 84.8%, 81.3%, and 0.89 of
      the Lemann Index at a cutoff level of 3.7. Patients with Lemann index >=3.7
      carried a higher risk of abdominal surgery (OR = 18.6; p < 0.001). Stricturing
      and penetrating disease were predictors for abdominal surgery, whereas antitumor
      necrosis factor treatment was associated with a significant reduction of surgical
      requirements. LIMITATIONS: This study was limited by its retrospective design.
      The ability of the Lemann index to predict the long-term risk of surgery was
      unknown. CONCLUSIONS: Lemann index at diagnosis is a reliable index to predict
      the risk of abdominal surgery in the first year after diagnosis of Crohn's
      disease. Patients with a high Lemann index might need closer follow-up or
      aggressive medical therapy. See Video Abstract at http://links.lww.com/DCR/A518.

PMID- 29337777
TI  - Rescue Diverting Loop Ileostomy: An Alternative to Emergent Colectomy in the
      Setting of Severe Acute Refractory IBD-Colitis.
AB  - BACKGROUND: Severe acute refractory colitis has traditionally been an indication
      for emergent colectomy in IBD, yet under these circumstances patients are at
      elevated risk for complications because of their heightened inflammatory state,
      nutritional deficiencies, and immunocompromised state. OBJECTIVE: We hypothesized
      that rescue diverting loop ileostomy may be a viable alternative to emergent
      colectomy, providing the opportunity for colonic healing and patient optimization
      before more definitive surgery. DESIGN: This was a retrospective case series.
      SETTINGS: The study was conducted at a single academic center. PATIENTS: Patients
      with severe acute medically refractory IBD-related colitis were included.
      INTERVENTION: Rescue diverting loop ileostomy was the intervening procedure. MAIN
      OUTCOME MEASURES: The primary outcome was avoidance of urgent/emergent colectomy.
      The secondary outcome was efficacy, defined by 3 clinical aims: 1) reduced
      steroid dependence or opportunity for bridge to medical rescue, 2) improved
      nutritional status, and 3) ability to undergo an elective laparoscopic definitive
      procedure or ileostomy reversal with colon salvage. RESULTS: Among 33 patients,
      14 had Crohn's disease and 19 had ulcerative colitis. Three patients required
      urgent/emergent colectomy, 2 with ulcerative colitis and 1 with Crohn's disease.
      Across both disease cohorts, >80% of patients achieved each clinical aim for
      efficacy: 88% reduced their steroid dependence or were able to bridge to medical
      rescue, 87% improved their nutritional status, and 82% underwent an elective
      laparoscopic definitive procedure or ileostomy reversal. A total of 4 patients
      (11.7%) experienced a postoperative complication following diversion, including 3
      surgical site infections and 1 episode of acute kidney injury. LIMITATIONS: The
      study was limited by being a single-center, retrospective series. CONCLUSIONS:
      Rescue diverting loop ileostomy in the setting of severe, refractory IBD-colitis
      is a safe and effective alternative to emergent colectomy. This procedure has
      acceptably low complication rates and affords patients time for medical and
      nutritional optimization before definitive surgical intervention. See Video
      Abstract at http://links.lww.com/DCR/A520.

PMID- 29337779
TI  - Does Ventral Rectopexy Improve Pelvic Floor Function in the Long Term?
AB  - BACKGROUND: Information is needed on long-term functional results, sequelas, and
      outcome predictors for laparoscopic ventral mesh rectopexy. OBJECTIVE: The
      purpose of this study was to evaluate long-term function postventral rectopexy in
      patients with external rectal prolapse or internal rectal prolapse in a large
      cohort and to identify the possible effects of patient-related factors and
      operative technical details on patient-reported outcomes. DESIGN: This was a
      retrospective review with a cross-sectional questionnaire study. SETTINGS: Data
      were collated from prospectively collected registries in 2 university and 2
      central hospitals in Finland. PATIENTS: All 508 consecutive patients treated with
      ventral rectopexy for external rectal prolapse or symptomatic internal rectal
      prolapse in 2005 to 2013 were included. INTERVENTIONS: A questionnaire concerning
      disease-related symptoms and effect on quality of life was used. MAIN OUTCOME
      MEASURES: Defecatory function measured by the Wexner score, the obstructive
      defecation score, and subjective symptom and quality-of-life evaluation using the
      visual analog scale were included. The effects of patient-related factors and
      operative technical details were assessed using multivariate analysis. RESULTS:
      The questionnaire response rate was 70.7% (330/467 living patients) with a median
      follow-up time of 44 months. The mean Wexner scores were 7.0 (SD = 6.1) and 6.9
      (SD = 5.6), and the mean obstructive defecation scores were 9.7 (SD = 7.6) and
      12.3 (SD = 8.0) for patients presenting with external rectal prolapse and
      internal rectal prolapse. Subjective symptom relief was experienced by 76% and
      reported more often by patients with external rectal prolapse than with internal
      rectal prolapse (86% vs 68%; p < 0.001). Complications occurred in 11.4% of
      patients, and the recurrence rate for rectal prolapse was 7.1%. LIMITATIONS: This
      study was limited by its lack of preoperative functional data and suboptimal
      questionnaire response rate. CONCLUSIONS: Ventral mesh rectopexy effectively
      treats posterior pelvic floor dysfunction with a low complication rate and an
      acceptable recurrence rate. Patients with external rectal prolapse benefit more
      from the operation than those with symptomatic internal rectal prolapse. See
      Video Abstract at http://links.lww.com/DCR/A479.

PMID- 29337778
TI  - Pelvic Pain and Quality of Life Before and After Laparoscopic Bowel Resection for
      Rectosigmoid Endometriosis: A Prospective, Observational Study.
AB  - BACKGROUND: Surgery for rectosigmoid endometriosis carries a substantial risk of
      short- and long-term complications, which has to be counterbalanced against the
      potential effect of the procedure. Prospective data are scarce in the field of
      deep infiltrating endometriosis surgery. OBJECTIVE: The study aimed to assess
      pelvic pain and quality of life before and after laparoscopic bowel resection for
      rectosigmoid endometriosis. DESIGN: The study involved prospectively collected
      data regarding pelvic pain and quality of life before and after surgery.
      SETTINGS: It was conducted at a tertiary endometriosis referral unit at Aarhus
      University Hospital. PATIENTS: A total of 175 women were included. INTERVENTION:
      Patients underwent laparoscopic bowel resection for endometriosis. MAIN OUTCOME
      MEASURES: Questionnaires for pain (Numerical Rating Scale) and quality of life
      (RAND Short Form-36) were answered before and 1 year after surgery. Data on
      analgesic and hormone treatment were collected. Preoperative and postoperative
      pelvic pain and quality-of-life scores were compared, and risk factors for
      improvement/worsening were identified. RESULTS: A total of 97.1% of the women
      completed the 1-year follow up. A significant decrease (p = 0.0001) was observed
      on all pelvic pain parameters. Most profound was the decrease in dyschezia. A
      significant improvement on all quality-of-life scores was observed (p = 0.0001).
      A surgical complication did not have a negative impact on outcome 1 year after
      surgery. The postoperative outcome was not related to the type of surgery.
      LIMITATIONS: This is an observational study without a control group. Risk factor
      data should be interpreted with caution, because the study was relatively
      underpowered for some of the rare outcomes. CONCLUSIONS: A significant and
      clinically relevant improvement in pelvic pain and quality of life 1 year after
      laparoscopic bowel resection for endometriosis was found. We strongly recommend
      surgery for rectosigmoid endometriosis that is unresponsive to conservative
      treatment. See Video Abstract at http://links.lww.com/DCR/A472.

PMID- 29337780
TI  - Efficacy and Safety of Sodium Picosulfate/Magnesium Citrate for Bowel Preparation
      in a Physically Disabled Outpatient Population: A Randomized, Endoscopist-Blinded
      Comparison With Ascorbic Acid-Enriched Polyethylene Glycol Solution Plus
      Bisacodyl (The PICO-MOVI Study).
AB  - BACKGROUND: Because of its volume, adequate bowel preparation remains problematic
      in physically unfit patients. OBJECTIVE: This study aimed to compare a small
      volume sodium picosulfate/magnesium citrate preparation with a 2-L ascorbic acid
      enriched polyethylene glycol solution plus bisacodyl. DESIGN: This study has a
      noninferiority design, assuming that ascorbic acid-enriched polyethylene glycol
      solution plus bisacodyl is 70% efficacious in achieving an Ottawa score <=7 and
      accepting a difference in success rate of <15% with a target enrollment of 146
      patients per group. SETTING: This study was conducted in an outpatient
      department. PATIENTS: Patients referred for diagnostic colonoscopy were randomly
      assigned. Key exclusion criteria were severe kidney disease, ASA class >=III, and
      hospital admission. INTERVENTION: Patients were randomly assigned to receive
      sodium picosulfate/magnesium citrate or ascorbic acid-enriched polyethylene
      glycol solution plus bisacodyl according to a split-dose regimen. Patients in the
      sodium picosulfate/magnesium citrate group received advice on the recommended 4-L
      fluid intake. Patients in the ascorbic acid-enriched polyethylene glycol solution
      plus bisacodyl group received 2 bisacodyl tablets 2 days before and advice on the
      additionally recommended 2-L fluid intake. MAIN OUTCOME MEASURES: To assess bowel
      cleansing adequacy, the Ottawa, Aronchick, and Boston scores were used.
      Colonoscopy quality measures were obtained. Safety was assessed for a 30-day
      follow-up period. RESULTS: Overall, 341 patients (169 men, mean age 57.0 years;
      BMI 26.2 kg/m) were included. Comorbidities were present in 76.2% of patients,
      and 75.4% of patients used medication. An adequate Ottawa score was obtained in
      81.4% and 75.8% of patients receiving ascorbic acid-enriched polyethylene glycol
      solution plus bisacodyl and sodium picosulfate/magnesium citrate (difference of
      5.6% (95% CI, -3.5 to -14.6; p = 0.023)), showing noninferiority of the sodium
      picosulfate/magnesium citrate therapy. Ottawa segmental scores were lower for
      sodium picosulfate/magnesium citrate in the right and transverse colon. In both
      groups, successful ileocecal intubation was achieved in 95%. No medication
      related adverse events were reported. LIMITATIONS: These results in a physically
      disabled ambulant population cannot be extrapolated to immobile, hospitalized
      patients. CONCLUSIONS: Sodium picosulfate/magnesium citrate proved to be
      noninferior to ascorbic acid-enriched polyethylene glycol solution plus bisacodyl
      in efficacy and safety. Timing of the colonoscopy and addition of bisacodyl to
      sodium picosulfate/magnesium citrate warrants further consideration. See Video
      Abstract at http://links.lww.com/DCR/A461.

PMID- 29337781
TI  - Comparison of Western and Asian Guidelines Concerning the Management of Colon
      Cancer.
AB  - BACKGROUND: Guidelines are important to standardize treatments and optimize
      outcomes. Several societies have published authoritative guidelines for patients
      with colon cancer, and a certain degree of variation can be predicted. OBJECTIVE:
      This study aims to compare Western and Asian guidelines for the management of
      colon cancer. DATA SOURCES: A literature review was performed following Preferred
      Reporting Items for Systematic Reviews and Meta-Analyses guidelines for studies
      published between 2010 and 2017 by the online resources from the official Web
      sites of the societies/panels. Sources included guidelines by European Society of
      Medical Oncology, the Japanese Society for Cancer of the Colon and Rectum, and
      the National Comprehensive Cancer Network. STUDY SELECTION: Only full-text
      studies and the latest guidelines dealing with colon cancer were included.
      Studies and guidelines were separately assessed by 2 authors, who independently
      identified discrepancies and areas for further research. These were discussed and
      agreed with by all the authors. MAIN OUTCOME MEASURES: The recommendations of the
      guidelines of each society were compared, seeking discrepancies and potential
      areas for improvement. RESULTS: Endoscopic techniques for the management of early
      colon cancer are discussed in detail in the Asian guidelines. Asian guidelines
      advocate extended (D3) lymphadenectomy on a routine basis in T3/T4 and in
      selected T2 patients, whereas such an approach is still under investigation in
      Western countries. Only US guidelines describe neoadjuvant chemotherapy and
      radiotherapy. All the guidelines recommend adjuvant treatment in selected stage
      II patients, but agreement exists that this is performed without solid evidence,
      because better outcomes are hypothesized based on studies including stage III or
      stage II/III patients. The role of cytoreductive surgery with intra-abdominal
      chemotherapy is dubious, and European guidelines only recommend it in the setting
      of trials. Asian guidelines endorse an aggressive surgical approach to peritoneal
      disease. Only US guidelines include a patient advocate in the drafting panel.
      LIMITATIONS: Bias may have arisen from country-specific socioeconomic and
      cultural issues, and from the latest available updates. CONCLUSIONS: Surgical
      approaches to colon cancer differ significantly among Western and Asian
      guidelines, reflecting different concepts of treatment. The role of adjuvant
      treatment in node-negative disease and quality-of-life assessment need further
      research.

PMID- 29337782
TI  - Laparoscopic Rectovaginopexy for Neorectal Prolapse After Transanal Total
      Mesorectal Excision.

PMID- 29337783
TI  - S1 Sacrectomy for Re-recurrent Rectal Cancer: Our Experience with Reconstruction
      Using an Expandable Vertebral Body Replacement Device.
AB  - INTRODUCTION: R0 resection is achieved by high sacrectomy for local recurrence of
      colorectal cancer, but significant rates of perioperative complications and long
      term patient morbidity are associated with this procedure. In this report, we
      outline our unique experience of using an expandable cage for vertebral body
      reconstruction following S1 sacrectomy in a 66-year-old patient with re-recurrent
      rectal cancer. We aim to highlight several key steps, with a view to improving
      postoperative outcomes. TECHNIQUE: A midline laparotomy was performed with the
      patient in supine Lloyd-Davies position, demonstrating recurrence of tumor at the
      S1 vertebral body. Subtotal vertebral body excision of S1 with sparing of the
      posterior wall and ventral foramina was completed by using an ultrasonic bone
      aspirator. Reconstruction was performed using an expandable corpectomy spacer
      system. The system was assembled and expanded in situ to optimally bridge the
      corpectomy. The device was secured into the L5 and S2 vertebrae by means of
      angled end plate screws superiorly and inferiorly. Bone grafts were positioned
      adjacent to the implant after this. RESULTS: Total operating time was 266 minutes
      with 350 mL of intraoperative blood loss. There were no immediate postoperative
      complications. The patient did not report any back pain at the time of discharge,
      and no neurological deficit was reported or identified. Postoperative CT scan
      showed excellent vertebral alignment and preservation of S1 height. CONCLUSION:
      We conclude that high sacrectomy with an expandable metal cage is feasible in the
      context of re-recurrent rectal cancer when consideration is given to the method
      of osteotomy and vertebral body replacement.

PMID- 29337784
TI  - The Sharp End of Pilonidal Disease.

PMID- 29337785
TI  - Authors Reply.

PMID- 29337786
TI  - Mechanical Bowel Preparation Before Colorectal Surgery in Enhanced Recovery
      Programs: Discrepancy Between the American and European Guidelines.

PMID- 29337787
TI  - Authors Reply.

PMID- 29337790
TI  - Can a Multicenter Pneumonia Zero Bundle Reduce Ventilator-Associated Pneumonias?

PMID- 29337789
TI  - Multicohort Analysis of Whole-Blood Gene Expression Data Does Not Form a Robust
      Diagnostic for Acute Respiratory Distress Syndrome.
AB  - OBJECTIVES: To identify a novel, generalizable diagnostic for acute respiratory
      distress syndrome using whole-blood gene expression arrays from multiple acute
      respiratory distress syndrome cohorts of varying etiologies. DATA SOURCES: We
      performed a systematic search for human whole-blood gene expression arrays of
      acute respiratory distress syndrome in National Institutes of Health Gene
      Expression Omnibus and ArrayExpress. We also included the Glue Grant gene
      expression cohorts. STUDY SELECTION: We included investigator-defined acute
      respiratory distress syndrome within 48 hours of diagnosis and compared these
      with relevant critically ill controls. DATA EXTRACTION: We used multicohort
      analysis of gene expression to identify genes significantly associated with acute
      respiratory distress syndrome, both with and without adjustment for clinical
      severity score. We performed gene ontology enrichment using Database for
      Annotation, Visualization and Integrated Discovery and cell type enrichment tests
      for both immune cells and pneumocyte gene expression. Finally, we selected a gene
      set optimized for diagnostic power across the datasets and used leave-one-dataset
      out cross validation to assess robustness of the model. DATA SYNTHESIS: We
      identified datasets from three adult cohorts with sepsis, one pediatric cohort
      with acute respiratory failure, and two datasets of adult patients with trauma
      and burns, for a total of 148 acute respiratory distress syndrome cases and 268
      critically ill controls. We identified 30 genes that were significantly
      associated with acute respiratory distress syndrome (false discovery rate < 20%
      and effect size >1.3), many of which had been previously associated with sepsis.
      When metaregression was used to adjust for clinical severity scores, none of
      these genes remained significant. Cell type enrichment was notable for bands and
      neutrophils, suggesting that the gene expression signature is one of acute
      inflammation rather than lung injury per se. Finally, an attempt to develop a
      generalizable diagnostic gene set for acute respiratory distress syndrome showed
      a mean area under the receiver-operating characteristic curve of only 0.63 on
      leave-one-dataset-out cross validation. CONCLUSIONS: The whole-blood gene
      expression signature across a wide clinical spectrum of acute respiratory
      distress syndrome is likely confounded by systemic inflammation, limiting the
      utility of whole-blood gene expression studies for uncovering a generalizable
      diagnostic gene signature.

PMID- 29337791
TI  - "Judge a Man by His Questions Rather Than by His Answers" Voltaire.

PMID- 29337792
TI  - Early Fluid Management in Sepsis: Yes.

PMID- 29337793
TI  - Expanding the Reach of Critical Care Pharmacists Globally.

PMID- 29337794
TI  - Noninvasive Treatment of Hypoxemic Respiratory Failure: Give It a Try... But Do
      Not Push Too Hard.

PMID- 29337795
TI  - Renal Decapsulation to Treat Ischemic Acute Kidney Injury: A New Twist in an Old
      Tale.

PMID- 29337796
TI  - Prolonged Infusions: The Significance of How.

PMID- 29337797
TI  - Beta-Lactam Therapeutic Drug Monitoring in the Critically Ill Children: Big
      Solution for Infections in Small People?

PMID- 29337798
TI  - (Not) Everybody Is Working for the Weekend.

PMID- 29337799
TI  - Ventilator Management Guided by Driving Pressure: A Better Way to Protect the
      Lungs?

PMID- 29337800
TI  - Old Wine in New Bottles: Continuous Versus Intermittent Renal Replacement Therapy
      in the ICU.

PMID- 29337801
TI  - Informed or Misinformed Consent?

PMID- 29337802
TI  - Mesenchymal Stromal Cell Therapy: Does the Source Matter?

PMID- 29337803
TI  - From Big Data to Artificial Intelligence: Harnessing Data Routinely Collected in
      the Process of Care.

PMID- 29337805
TI  - Donation After Cardiocirculatory Determination of Death Requires "Timely" Rather
      Than "Early" Referral.

PMID- 29337804
TI  - The Association Between Ventilator Dyssynchrony, Delivered Tidal Volume, and
      Sedation Using a Novel Automated Ventilator Dyssynchrony Detection Algorithm.
AB  - OBJECTIVE: Ventilator dyssynchrony is potentially harmful to patients with or at
      risk for the acute respiratory distress syndrome. Automated detection of
      ventilator dyssynchrony from ventilator waveforms has been difficult. It is
      unclear if certain types of ventilator dyssynchrony deliver large tidal volumes
      and whether levels of sedation alter the frequency of ventilator dyssynchrony.
      DESIGN: A prospective observational study. SETTING: A university medical ICU.
      PATIENTS: Patients with or at risk for acute respiratory distress syndrome.
      INTERVENTIONS: Continuous pressure-time, flow-time, and volume-time data were
      directly obtained from the ventilator. The level of sedation and the use of
      neuromuscular blockade was extracted from the medical record. Machine learning
      algorithms that incorporate clinical insight were developed and trained to detect
      four previously described and clinically relevant forms of ventilator
      dyssynchrony. The association between normalized tidal volume and ventilator
      dyssynchrony and the association between sedation and the frequency of ventilator
      dyssynchrony were determined. MEASUREMENTS AND MAIN RESULTS: A total of 4.26
      million breaths were recorded from 62 ventilated patients. Our algorithm detected
      three types of ventilator dyssynchrony with an area under the receiver operator
      curve of greater than 0.89. Ventilator dyssynchrony occurred in 34.4% (95% CI,
      34.41-34.49%) of breaths. When compared with synchronous breaths, double
      triggered and flow-limited breaths were more likely to deliver tidal volumes
      greater than 10 mL/kg (40% and 11% compared with 0.2%; p < 0.001 for both
      comparisons). Deep sedation reduced but did not eliminate the frequency of all
      ventilator dyssynchrony breaths (p < 0.05). Ventilator dyssynchrony was
      eliminated with neuromuscular blockade (p < 0.001). CONCLUSION: We developed a
      computerized algorithm that accurately detects three types of ventilator
      dyssynchrony. Double-triggered and flow-limited breaths are associated with the
      frequent delivery of tidal volumes of greater than 10 mL/kg. Although ventilator
      dyssynchrony is reduced by deep sedation, potentially deleterious tidal volumes
      may still be delivered. However, neuromuscular blockade effectively eliminates
      ventilator dyssynchrony.

PMID- 29337806
TI  - The authors reply.

PMID- 29337807
TI  - Extracorporeal Membrane Oxygenation-Associated Infections: Carefully Consider
      Cannula Infections!

PMID- 29337808
TI  - The authors reply.

PMID- 29337809
TI  - Untargeted Antifungal Treatment in the ICU: Changing Definitions and Labels Do
      Not Change the Evidence.

PMID- 29337810
TI  - The authors reply.

PMID- 29337811
TI  - Individualizing Cerebral Perfusion Pressure Targets.

PMID- 29337812
TI  - The authors reply.

PMID- 29337813
TI  - Heparin-Free Regional Anticoagulation: There Are Significant Differences Between
      Citrate-Containing Dialysate and Regional Citrate Anticoagulation.

PMID- 29337814
TI  - The authors reply.

PMID- 29337815
TI  - Impact of Moderate Hyperchloremia on Clinical Outcomes in Intracerebral
      Hemorrhage Patients. Is There Still Room for Continuous Infusion of 3% Hypertonic
      Saline?

PMID- 29337816
TI  - The authors reply.

PMID- 29337817
TI  - Burnout Research: Eyes Wide Shut.

PMID- 29337818
TI  - The authors reply.

PMID- 29337819
TI  - Is Oxygenation Really an Intrinsic Predictive Factor of Mortality in Patients
      Undergoing Extracorporeal Life Support?

PMID- 29337820
TI  - The authors reply.

PMID- 29337821
TI  - Systolic Dysfunction Following Traumatic Brain Injury.

PMID- 29337822
TI  - The authors reply.

PMID- 29337823
TI  - Noninvasive Ventilation in Acute Respiratory Failure: Who Will Benefit?

PMID- 29337824
TI  - The authors reply.

PMID- 29337825
TI  - Effect of Patient- and Family-Centered Care Interventions on ICU Length of Stay.

PMID- 29337826
TI  - The author replies.

PMID- 29337827
TI  - Severe Burnout Is Common Among Critical Care Physician Assistants: Retraction.

PMID- 29337828
TI  - Semiautomated Subretinal Fluid Injection Method Using Viscous Fluid Injection
      Mode.

PMID- 29337829
TI  - Estimation of Repetitions to Failure for Monitoring Resistance Exercise
      Intensity: Building a Case for Application.
AB  - Hackett, DA, Cobley, SP, and Halaki, M. Estimation of repetitions to failure for
      monitoring resistance exercise intensity: Building a case for application. J
      Strength Cond Res 32(5): 1352-1359, 2018-The purpose of this study was to (a)
      examine the accuracy of Estimated Repetitions to Failure (ERF) during resistance
      exercise between 2 sessions and (b) compare ERF to rating of perceived exertion
      (RPE) for determining proximity to momentary failure. Forty-eight adults with
      recreational resistance training experience performed 3 sets of 10 repetitions at
      70% one-repetition maximum (1RM) and 80% 1RM for the chest press and leg press,
      respectively. At the completion of each set, participants reported their ERF and
      then continued repetitions to failure to determine actual repetitions to failure
      (ARF). Two sessions of the same experimental protocol were performed with 48
      hours between bouts. For session 1, error in ERF was greater during the first
      sets compared with third sets for the chest press (2.0 vs. 0.6 repetitions and p
      < 0.001) and leg press (3.1 vs. 1.6 repetitions and p < 0.001). No differences
      for error in ERF were observed between sessions 1 and 2 for the chest press (p >
      0.944); however, less error in ERF was found for the leg press during set 1 of
      session 2 (3.1 vs. 1.9 repetitions and p < 0.013). Strong to very strong
      relationships were found between ERF and ARF (r = 0.59-0.87 and p < 0.01),
      whereas most relationships for RPE and ARF were small to moderate (r = 0.32 to 
      0.42 and p < 0.01). Improvement in the accuracy of ERF after a single training
      bout is minimal, whereas ERF compared with RPE seems to have greater sensitivity
      for discriminating momentary failure.

PMID- 29337830
TI  - Exploring the effects of playing formations on tactical behaviour and external
      workload during football small-sided games.
AB  - This study aimed to identify the effects of playing formations on tactical
      behaviour and external workload during football small-sided games. Twenty-three
      semi-professional footballers integrated three different playing formations in a
      7-a-side small-sided game, according to their specific player positions: team
      4:3:0 (4 defenders, 3 midfielders); team 4:1:2 (4 defenders, 1 midfielder, 2
      forwards); and team 0:4:3 (4 midfielders, 3 forwards). Based on players' movement
      trajectories, the following individual and collective tactical variables were
      calculated: total distance covered and distance covered while walking, jogging,
      running and sprinting, distance from each player to both own and opponent's team
      centroid (Dist CG and Dist OPP CG, respectively), individual area, team length,
      team width and surface area. Approximate entropy (ApEn) was computed to identify
      the regularity of each variable. The team 4:3:0 promoted players' space
      exploration with moderate physical efforts. The team 4:1:2 promoted compactness
      and regularity of the team with increase in the physical efforts. The team 0:4:3
      promoted team balance and adaptability on space coverage with increase in
      physical efforts. Concluding, different playing formations support different game
      dynamics, and variations on external load were directly linked with the
      variations on tactical behaviour. The analysis tactical behaviour through
      quantification of variability of patterns of play and quantification of distance
      covered at different velocities were the most useful information for the analysis
      of the effects of practice task manipulations. Therefore, in a practical sense,
      strength and conditioning coaches should plan and monitor these tasks in
      interaction with the head coaches.

PMID- 29337831
TI  - Acute Effects of a Caffeine-Containing Supplement on Anaerobic Power and
      Subjective Measurements of Fatigue in Recreationally Active Men.
AB  - Hahn, CJ, Jagim, AR, Camic, CL, and Andre, MJ. Acute effects of a caffeine
      containing supplement on anaerobic power and subjective measurements of fatigue
      in recreationally active men. J Strength Cond Res 32(4): 1029-1035, 2018-Studies
      show mixed results for the effects of caffeine on performance, warranting further
      investigation. The purpose of this study was to examine the acute effects of a
      caffeine-containing supplement on anaerobic power and subjective measurements of
      fatigue during resisted sprinting on men. Fourteen recreationally active men (N =
      14; [mean +/- SD], age: 21.0 +/- 0.7 years, height: 178.5 +/- 5.1 cm, body mass:
      77.3 +/- 9.6 kg, and percent body fat: 12.6 +/- 4.8%) participated in a double
      blind, placebo-controlled, within-subject crossover design study. The first visit
      required each participant to complete 3 sets of practice sprints on a
      nonmotorized treadmill ranging from 10 to 20 seconds. During the second visit,
      participants completed 5 more practice sprints ranging from 15 to 25 seconds.
      During the third and fourth visits, participants ingested one serving of a
      caffeine-containing or placebo beverage (the opposite beverage was consumed
      during the fourth visit), rested for 20 minutes, and completed a dynamic warm-up
      before sprinting. Anaerobic power was assessed using a countermovement vertical
      jump and nonmotorized treadmill sprint test. Psychological variables were scored
      using a 5-point Likert scale. No significant (p <= 0.05) differences were
      observed between conditions for average (p = 0.22) or peak power (p = 0.43). Both
      conditions resulted in a significant increase in fatigue, although the increase
      was less for the caffeine condition (caffeine [INCREMENT] = 0.93 and placebo
      [INCREMENT] = 1.71). These findings indicated that the caffeine-containing
      supplement improved perceived measures of fatigue but not power indices assessed
      through vertical jump or nonmotorized treadmill sprinting. The consumption of a
      caffeine beverage may be beneficial for reducing perceived fatigue during acute
      anaerobic exercise, particularly when repeated sprints are used.

PMID- 29337832
TI  - Comparison of Step-by-Step Kinematics in Repeated 30-m Sprints in Female Soccer
      Players.
AB  - van den Tillaar, R. Comparison of step-by-step kinematics in repeated 30-m
      sprints in female soccer players. J Strength Cond Res 32(7): 1923-1928, 2018-The
      aim of this study was to compare kinematics in repeated 30-m sprints in female
      soccer players. Seventeen subjects performed seven 30-m sprints every 30 seconds
      in one session. Kinematics was measured with an infrared contact mat and laser
      gun, and running times with an electronic timing device. The main findings were
      that sprint times increased in the repeated-sprint ability test. The main changes
      in kinematics during the repeated-sprint ability test were increased contact time
      and decreased step frequency, whereas no change in step length was observed. The
      step velocity increased in almost each step until the 14th, which occurred around
      22 m. After this, the velocity was stable until the last step, when it decreased.
      This increase in step velocity was mainly caused by the increased step length and
      decreased contact times. It was concluded that the fatigue induced in repeated 30
      m sprints in female soccer players resulted in decreased step frequency and
      increased contact time. Using this approach in combination with a laser gun and
      infrared mat for 30 m makes it very easy to analyze running kinematics in
      repeated sprints in training. This extra information gives the athlete, coach,
      and sports scientist the opportunity to give more detailed feedback and helps to
      target these changes in kinematics better to enhance repeated-sprint performance.

PMID- 29337833
TI  - Effects of Plyometric and Resistance Training on Muscle Strength, Explosiveness
      and Neuromuscular Function in Young Adolescent Soccer Players.
AB  - This study examined the effect of 8-weeks of free-weight-resistance (RT) and
      plyometric (PLYO) training on maximal strength, explosiveness and jump
      performance compared with no added training (CON), in young male soccer players.
      Forty-one 11[FIGURE DASH]13-year-old soccer players were divided into three
      groups (RT, PLYO, CON). All participants completed isometric and dynamic (240
      degrees /s) knee extensions pre- and post-training. Peak torque (pT), peak rate
      of torque development (pRTD), electromechanical-delay (EMD), rate of muscle
      activation (Q50), m. vastus-lateralis thickness (VLT), and jump performance were
      examined. pT, pRTD and jump performance significantly improved in both training
      groups. Training resulted in significant (p<0.05) increases in isometric pT (23.4
      vs. 15.8%) and pRTD (15.0 vs. 17.6%), in RT and PLYO, respectively. During
      dynamic contractions, training resulted in significant increases in pT (12.4 and
      10.8% in RT and PLYO, respectively), but not pRTD. Jump performance increased in
      both training groups (RT=10.0%, PLYO=16.2%), with only PLYO significantly
      different from CON. Training resulted in significant increases in VLT (RT=6.7%.
      PLYO=8.1%). There were no significant EMD changes. In conclusion, 8-week free
      weight resistance and plyometric training resulted in significant improvements in
      muscle strength and jump performance. Training resulted in similar muscle
      hypertrophy in the two training modes, with no clear differences in muscle
      performance. Plyometric training was more effective in improving jump
      performance, while free-weight resistance training was more advantageous in
      improving peak torque, where the stretch reflex was not involved.

PMID- 29337834
TI  - Manipulating Field Dimensions During Small-sided Games Impacts the Technical and
      Physical Profiles of Australian Footballers.
AB  - Brock, F, Christopher, J, Harry, B, and Carl, WT. Manipulating field dimensions
      during small-sided games impacts the technical and physical profiles of
      Australian footballers. J Strength Cond Res 32(7): 2039-2044, 2018-This study
      investigated the effect of manipulating field dimensions on the technical and
      physical profiles of Australian football (AF) players during small-sided games
      (SSGs). A total of 40 male players (23.9 +/- 3.5 years) participated in 3, five-a
      side SSGs; defined as "small" (20 * 30 m; 600 m), "medium" (30 * 40 m; 1,200 m),
      and "large" (40 * 50 m; 2,000 m). Notational analyses enabled the quantification
      of technical skill indicators, whereas physical activity profiles were measured
      using microtechnology, resulting in 18 criterion variables. A multivariate
      analysis of variance modeled the main effect of field dimension on the criterion
      variables. A significant main effect was observed (V = 1.032; F38, 102 = 2.863; p
      <= 0.05), with the "small" and "medium" SSGs generating more turnovers and
      ineffective handballs relative to the "large" SSG. Furthermore, the "small" SSG
      generated more tackles and fewer bounces compared with the "large" SSG. The
      "large" SSG generated a greater absolute distance, relative distance, maximum
      velocity, PlayerLoad, and distance >4.16 m.s compared with the "small" and
      "medium" SSGs. These results provide AF coaches with insights into how task
      constraint manipulation impacts the technical and physical profiles of players
      during small-sided game-play. Thus, coaches and physical performance specialists
      could use this information to assist with the tactical periodization of technical
      complexity and physical load at different phases of the AF season.

PMID- 29337835
TI  - Promethazine and Oral Midazolam Preanesthetic Children Medication.
AB  - AIMS: Several kinds of drugs have been investigated in preschool children as a
      preanesthetic sedation after various routes of administration for surgeries. This
      study aims to compare the efficacy of promethazine and oral midazolam for
      premedication in children aged 3 to 9 years who were scheduled for surgeries.
      METHODS: This is a double-blind randomized controlled study conducted on 93
      patients between the age of 3 and 9 years at Loresten University of Medical
      Sciences Teaching Hospital, Khoramabad, Iran. The subjects were grouped into P
      (promethazine), M (midazolam), and C (control). About 0.3 mg/kg of oral
      promethazine was administered to patients in group P, 0.5 mg/kg of oral midazolam
      was administered to patients in group M, and 3 mL of normal saline as placebo was
      administered to patients in group C. Patient satisfaction, sedation and emotional
      score, systolic blood pressure (SBP), diastolic blood pressure, respiratory rate
      (RR), and heart rate (HR) were recorded. RESULTS: There was no statistically
      significant difference among the 3 groups. However, the period after medication,
      it was observed that SBP, diastolic blood pressure, RR, and HR in group C were
      statistically significantly higher than those in groups M and P. These 2 groups
      are similar in terms of SBP, RR, and HR. The emotional scores were comparable for
      the 2 groups. It was between 3.97 +/- 0.6 to 1.7 +/- 0.5 in group M and from 3.45
      +/- 1.17 to 2.745 +/- 0.997 in group P in a Kruskal-Wallis test. CONCLUSIONS:
      This study shows that both test groups reduce stress at the time of anesthetic
      induction and separation from their parents with similar effect. Both of the
      anesthetics are easily administered without the necessity of an additional
      equipment. A shorter period to maximal sedation for midazolam is an advantage,
      thus, making the drug helpful, mostly in the outpatient setting.

PMID- 29337836
TI  - Fever as a Presenting Symptom in Children Evaluated for Ileocolic
      Intussusception: The Experience of a Large Tertiary Care Pediatric Hospital.
AB  - BACKGROUND: Intussusception is the most common cause of intestinal obstruction in
      young children, and delayed diagnosis may lead to bowel perforation. The
      objective of this study was to determine the prevalence of fever in patients with
      ileocolic intussusception and to determine its utility as a predictive symptom.
      METHODS: This was a 3-year retrospective study, at a tertiary care center, of
      children aged 1 month to 6 years, presenting with possible intussusception.
      Charts were reviewed for clinical signs and symptoms at presentation, and all
      diagnostic studies were retrieved. A pediatric radiologist reviewed all
      ultrasounds. RESULTS: A total of 488 ultrasounds were performed on suspicion of
      intussusception. In 30 patients with confirmed ileocolic intussusception, mean
      age was 27 months and all were successfully reduced by air enema. Of 118 patients
      with fever, 2 had confirmed intussusception, 1 with pneumonia and 1 with acute
      otitis media, compared with 116 febrile patients with negative ultrasounds (P <
      0.05). CONCLUSIONS: Traditional teaching is that intussusception presents as
      intermittent colicky abdominal pain, red currant jelly stool, vomiting, and a
      palpable abdominal mass, but it is important to remember that this classic triad
      is a very late finding and this condition should be recognized before the
      development of these findings. The concurrence of fever can help to rule out the
      possibility of intussusception and prompt the health care professional to search
      diligently for alternative infectious etiologies but cannot eliminate the
      possibility, especially when other findings suggestive of intussusception are
      present.

PMID- 29337837
TI  - Accidental Rivaroxaban Intoxication in a Boy: Some Lessons in Managing New Oral
      Anticoagulants in Children.
AB  - Novel oral anticoagulants offer equivalent or improved therapeutic profiles
      compared with warfarin, with less risk of bleeding, no interactions with food,
      and no need for routine laboratory monitoring. Caution must be exercised in using
      these drugs in certain patient populations, for example, renal insufficiency,
      those receiving additional antithrombotic therapy, those with questionable
      compliance, children, and those with a high risk of gastrointestinal bleeding.
      One of the novel oral anticoagulants, rivaroxaban, is a direct Factor Xa
      inhibitor, used to reduce risk of stroke and systemic embolism in patients with
      nonvalvular atrial fibrillation, deep vein thrombosis, and pulmonary embolism. We
      report a child who presented abnormal coagulation tests after unintended
      ingestion of 4 tablets of rivaroxaban. The patient was treated with fresh frozen
      plasma as well as admitted to intensive care and improved several hours later. We
      discuss his presentation and review of the literature on this topic.

PMID- 29337838
TI  - Comparison Between Small and Large Bowel Intussusception in Children: The
      Experience of a Large Tertiary Care Pediatric Hospital.
AB  - BACKGROUND: Intussusception is the most common cause of intestinal obstruction in
      young children, and delayed diagnosis may lead to serious sequelae. The objective
      of this study was to determine the prevalence of ileoileal intussusception and to
      document and compare clinical outcomes with ileocolic intussusception. METHODS: A
      retrospective cohort study of children with an abdominal ultrasound that
      diagnosed intussusception. Clinical data and diagnostic studies were retrieved,
      to compare ileoileal with ileocolic intussusception. RESULTS: A total of 488
      patients were evaluated with an abdominal ultrasound on suspicion of
      intussusception; 54 (11%) had ileoileal intussusception and 30 (6%) ileocolic
      intussusception. The significant features distinguishing the 2 conditions were
      fever, more common in patients with ileoileal intussusception, and an abdominal
      mass, which was papable more commonly in ileocolic intussusception. None of the
      ileoileal intussusception patients required surgical intervention, and all were
      discharged without complication. CONCLUSIONS: With recent advances in abdominal
      ultrasound, the diagnosis of ileoileal intussusception has become easier than
      before. Patients presenting with small bowel intussusception may not need any
      immediate intervention. The presence of fever supports the diagnosis of ileoileal
      intussusception.

PMID- 29337839
TI  - Serum Admission 25-Hydroxyvitamin D Levels and Outcomes in Initially Non-Septic
      Critically Ill Patients.
AB  - INTRODUCTION: To examine whether very low levels of 25-hydroxyvitamin D {25(OH)D}
      upon admission to the intensive care unit (ICU) are associated with worse
      outcomes. METHODS: Retrospective observational cohort study of critically ill
      patients treated in a multidisciplinary ICU. Two hundred twenty seven initially
      non-septic, critically ill patients, in whom 25-hydroxyvitamin D was measured at
      ICU admission. An additional group of 192 healthy subjects was also used.
      Patients were categorized according to their vitamin D levels at admission; the
      two patient groups were those with severely low 25-hydroxyvitamin D levels (<7
      ng/mL, N = 101) and those with vitamin D levels >=7 ng/mL, N = 126. RESULTS: ICU
      admission 25-hydroxyvitamin D levels of critically ill patients were much lower
      than those of healthy subjects (P < 0.0001). The median time to sepsis for the
      two patient groups did not differ, nor did the length of ICU stay (days). Both
      groups exhibited similar hospital mortality rates. However, among the fraction of
      patients who eventually became septic (N = 145), the odds ratio (OR) for
      developing respiratory infections in patients with admission vitamin levels < 7
      ng/mL compared with patients with admission vitamin D levels >=7 ng/mL was 5.25
      {95% confidence interval (CI) 1.5-18.32, P = 0.009}. CONCLUSIONS: Initially non
      septic critically ill patients appear to have very low ICU admission 25
      hydroxyvitamin D levels. Among critically ill patients, severely low vitamin D
      levels (<7 ng/mL) at ICU admission do not predict sepsis development, increased
      risk of in-hospital mortality, or longer stay in the ICU. However, these severely
      low admission vitamin D levels in patients who will eventually develop sepsis are
      associated with development of respiratory tract infections.

PMID- 29337840
TI  - Targeted Temperature Management at 33 degrees C or 36 degrees C Produces
      Equivalent Neuroprotective Effects in the Middle Cerebral Artery Occlusion Rat
      Model of Ischemic Stroke.
AB  - Targeted temperature management (TTM, 32 degrees C to 36 degrees C) is one of the
      most successful achievements in modern resuscitation medicine. It has become
      standard treatment for survivors of sudden cardiac arrest to minimize secondary
      brain damage. TTM at 36 degrees C is just as effective as TTM at 33 degrees C and
      is actually preferred because it reduces adverse TTM-associated effects. TTM also
      likely has direct neuroprotective effects in ischemic brains in danger of stroke.
      It remains unclear, however, whether higher temperature TTM is equally effective
      in protecting the brain from the effects of stroke. Here, we asked whether TTM at
      36 degrees C is as effective as TTM at 33 degrees C in improving outcomes in a
      middle cerebral artery occlusion (MCAO) model of ischemic stroke. After dividing
      rats randomly into MCAO, MCAO+33 degrees C TTM, MCAO+36 degrees C TTM, and sham
      groups, we subjected all of them except for the sham group to MCAO for 3 h (for
      the behavioral tests) or 4 h (for all other biochemical analyses). We found TTM
      protocols at both 33 degrees C and 36 degrees C to produce comparable reductions
      of infarct volumes in the MCAO territory and equally attenuate the extracellular
      release of high mobility group box 1 in postischemic brains. Both the TTM
      conditions prevent the mRNA induction of a major pro-inflammatory cytokine,
      tissue necrosis factor-alpha, in the ischemic penumbra region. Finally, both the
      TTM protocols produce similar improvements in neurological outcomes in rats, as
      measured by a battery of behavior tests 21 h after the start of reperfusion.
      These data acquired in a rat MCAO model suggest TTM at 36 degrees C has excellent
      therapeutic potential for improving clinical outcomes for patients with acute
      ischemic stroke.

PMID- 29337841
TI  - Frequency and Severity of Acute Allergic-Like Reactions to Intravenously
      Administered Gadolinium-Based Contrast Media in Children.
AB  - OBJECTIVES: The purpose of this study is to determine the frequency and severity
      of acute allergic-like reactions to gadolinium-based contrast media (GBCM) in
      children before, during, and after the transition from gadopentetate dimeglumine
      to gadoterate meglumine as our primary clinical GBCM. MATERIALS AND METHODS:
      Institutional review board approval was obtained for this Health Insurance
      Portability and Accountability Act-compliant retrospective investigation.
      Allergic-like reactions to GBCM in pediatric patients were retrospectively
      assessed from January 2009 to January 2017, which included a departmental change
      of GBCM from gadopentetate dimeglumine to gadoterate meglumine. Allergic-like
      reactions were identified from departmental and hospital databases. The number of
      doses of GBCM was obtained from billing data. Allergic-like reaction frequencies
      for each GBCM were calculated and compared using the chi-squared test. RESULTS: A
      total of 32,365 administrations of GBCM occurred during the study period (327 for
      gadofosveset trisodium; 672 for gadoxetate disodium; 12,012 for gadoterate
      meglumine; and 19,354 for gadopentetate dimeglumine). Allergic-like reactions
      occurred after 21 (0.06%) administrations. Reaction frequencies were not
      significantly different among the GBCM (0.3% gadofosveset trisodium; 0%
      gadoxetate disodium, 0.06% gadoterate meglumine, 0.08% gadopentetate dimeglumine;
      P > 0.05). Ten (47.6%) reactions were mild, 10 (47.6%) were moderate, and 1
      (4.8%) was severe. The overall reaction frequency peaked during the 6-month
      transition period from gadopentetate dimeglumine to gadoterate meglumine (0.20%),
      compared with 0.07% pretransition (P = 0.048) and 0.04% posttransition (P =
      0.0095). CONCLUSION: Allergic-like reactions to GBCM in children are rare.
      Gadoterate meglumine has a reaction frequency that does not significantly differ
      from other GBCMs. During the transition from gadopentetate dimeglumine to
      gadoterate meglumine, an increase in the frequency of reported allergic-like
      reactions was observed, likely reflective of the Weber effect.

PMID- 29337842
TI  - Perioperative Coagulation Management in Liver Transplant Recipients.
AB  - We review contemporary coagulation management for patients undergoing liver
      transplantation. A better understanding of the complex physiologic changes that
      occur in patients with end-stage liver disease has resulted in significant
      advances in anesthetic and coagulation management. A group of internationally
      recognized experts have critically evaluated current approaches for coagulopathy
      detection and management. Strategies for blood component and factor replacement
      have been evaluated and recommended therapies proposed. Pharmacologic treatment
      and prevention of coagulopathy, management of patients receiving antiplatelet
      medications, and the role of transesophageal echocardiography for early detection
      and management of thromboses are presented.

PMID- 29337843
TI  - Evaluation of a Decision Tree for Efficient Antenatal Red Blood Cell Antibody
      Screening.
AB  - BACKGROUND: Hemolytic disease of the fetus and newborn due to maternal red blood
      cell alloimmunization can have serious consequences. Because early detection
      enables careful monitoring of affected pregnancies, programs to routinely screen
      all pregnant women have been widely adopted. Due to the low prevalence of
      alloimmunization, these require large investments of resources to detect a small
      number of cases. METHODS: We conducted a validation study of a decision tree
      developed in the Netherlands for determining whether to screen for
      alloimmunization. In a Swedish cohort, we compared the performance of that
      decision tree to two alternative models that used maternal characteristics,
      obstetric history, and transfusion history to identify high-risk women for
      screening or low-risk women who might be exempt from screening. The models were
      compared for predictive ability and potential reduction in the volume of
      screening. RESULTS: The decision tree applied to our study population identified
      89% of alloimmunized women with a negative predictive value (NPV) of 99.7% by
      screening 62% of the population. To achieve the same NPV, our model exempting low
      risk women captured 90% of alloimmunizations by screening 63% of the population.
      In contrast, the model identifying high-risk women for screening while
      maintaining a similar NPV captured 63% of alloimmunized women by screening 20% of
      the population. CONCLUSIONS: We validated that an existing decision tree for
      selecting women for maternal screening performed well in our population,
      identifying a large proportion of women who became alloimmunized, with a
      predictive performance almost identical to that of a more elaborate model.

PMID- 29337844
TI  - Melanoma of the Skin in the Danish Cancer Registry and the Danish Melanoma
      Database: A Validation Study.
AB  - BACKGROUND: The nationwide Danish Cancer Registry and the Danish Melanoma
      Database both record data on melanoma for purposes of monitoring, quality
      assurance, and research. However, the data quality of the Cancer Registry and the
      Melanoma Database has not been formally evaluated. METHODS: We estimated the
      positive predictive value (PPV) of melanoma diagnosis for random samples of 200
      patients from the Cancer Registry (n = 200) and the Melanoma Database (n = 200)
      during 2004-2014, using the Danish Pathology Registry as "gold standard"
      reference. We further validated tumor characteristics in the Cancer Registry and
      the Melanoma Database. Additionally, we estimated the PPV of in situ melanoma
      diagnoses in the Melanoma Database, and the sensitivity of melanoma diagnoses in
      2004-2014. RESULTS: The PPVs of melanoma in the Cancer Registry and the Melanoma
      Database were 97% (95% CI = 94, 99) and 100%. The sensitivity was 90% in the
      Cancer Registry and 77% in the Melanoma Database. The PPV of in situ melanomas in
      the Melanoma Database was 97% and the sensitivity was 56%. In the Melanoma
      Database, we observed PPVs of ulceration of 75% and Breslow thickness of 96%. The
      PPV of histologic subtypes varied between 87% and 100% in the Cancer Registry and
      93% and 100% in the Melanoma Database. The PPVs for anatomical localization were
      83%-95% in the Cancer Registry and 93%-100% in the Melanoma Database.
      CONCLUSIONS: The data quality in both the Cancer Registry and the Melanoma
      Database is high, supporting their use in epidemiologic studies.

PMID- 29337845
TI  - Statistical Power for Trend-in-trend Design.

PMID- 29337846
TI  - 25-Hydroxyvitamin D and Long Menstrual Cycles in a Prospective Cohort Study.
AB  - BACKGROUND: Vitamin D insufficiency is associated with subfertility and prolonged
      estrus cycles in animals, but humans have not been well studied. METHODS: A
      prospective time-to-pregnancy study, Time to Conceive (2010-2015), collected up
      to 4 months of daily diary data. Participants were healthy, late reproductive
      aged women in North Carolina who were attempting pregnancy. We examined menstrual
      cycle length as a continuous variable and in categories: long (35+ days) and
      short (<=25 days). Follicular phase length and luteal phase length were
      categorized as long (18+ days) or short (<=10 days). We estimated associations
      between those lengths and serum 25-hydroxyvitamin D (25[OH]D) using linear mixed
      models and marginal models. RESULTS: There were 1,278 menstrual cycles from 446
      women of whom 5% were vitamin D deficient (25[OH]D, <20 ng/ml), 69% were between
      20 and 39 ng/ml, and 26% were 40 ng/ml or higher. There was a dose-response
      association between vitamin D levels and cycle length. Compared with the highest
      25(OH)D level (>=40 ng/ml), 25(OH)D deficiency was associated with almost three
      times the odds of long cycles (adjusted odds ratio [aOR] = 2.8 [95% confidence
      interval (CI) = 1.0, 7.5]). The aOR was 1.9 (1.1, 3.5) for 20 to <30 ng/ml. The
      probability of a long follicular phase and the probability of a short luteal
      phase both increased with decreasing 25(OH)D. CONCLUSIONS: Lower levels of
      25(OH)D are associated with longer follicular phase and an overall longer
      menstrual cycle. Our results are consistent with other evidence supporting
      vitamin D's role in the reproductive axis, which may have broader implications
      for reproductive success.

PMID- 29337847
TI  - HIV Care Continuum Disparities Among Black Bisexual Men and the Mediating Effect
      of Psychosocial Comorbidities.
AB  - INTRODUCTION: Differences across the HIV care continuum between men who have sex
      with men and women (MSMW) and men who have sex with men only (MSMO) are emerging
      in recent literature but have not been comprehensively documented among black
      MSM. Although MSMW have lower HIV prevalence than MSMO, they are more likely to
      be HIV-positive unaware and be virally unsuppressed. Explanatory factors for
      these differences have not previously been assessed. METHODS: Between 2014 and
      2016, we surveyed sexually active black MSM 18 years or older at Black Gay Pride
      events in 6 U.S. cities (n = 3881), 1229 of whom either self-reported HIV
      positive status or tested HIV-positive onsite. We compared HIV-positive MSMW (n =
      196) with HIV-positive MSMO (n = 1033) by HIV-positive unaware status, HIV care
      uptake, and viral load suppression. We conducted multivariable logistic
      regressions and built a structural equation model assessing mediating effects of
      psychosocial comorbidities (violence victimization, depression, and polydrug use)
      on the relationship between MSMW status and unsuppressed virus. RESULTS: MSMW
      were more likely than MSMO to be HIV-positive unaware [adjusted odds ratio (aOR)
      = 2.17; 95% confidence interval (CI): 1.58 to 3.00]. Among those who were HIV
      positive aware (n = 720), MSMW were more likely to report never receiving HIV
      care (aOR = 2.74; 95% CI: 1.05 to 7.16) and to report detectable viral loads (aOR
      = 2.34; 95% CI: 1.31 to 4.19). Psychosocial comorbidities significantly mediated
      (P = 0.01) the relationship between MSMW status and unsuppressed virus.
      DISCUSSION: Black MSMW were less likely than black MSMO to uptake biomedical care
      and secondary prevention. Biobehavioral intervention development specific to HIV
      positive black MSMW will be most successful if psychosocial comorbidities are
      also addressed.

PMID- 29337848
TI  - Transmission Networks of HCV Genotype 1a Enriched With Pre-existing Polymorphism
      Q80K Among HIV-Infected Patients With Acute Hepatitis C in Poland.
AB  - BACKGROUND: Hepatitis C virus (HCV) resistance-associated variants (RAVs) have
      been shown to adversely affect treatment response of direct-acting antivirals.
      Identifying pre-existing RAVs and transmission networks among HIV/HCV genotype 1
      (G1)-infected patients from Poland will assist in shaping surveillance strategies
      for HCV. METHODS: NS3 and NS5A sequences were obtained from samples of 112 direct
      acting antiviral-naive G1 patients (45 G1a and 67 G1b), of which 74 were
      chronically infected and 38 were diagnosed with acute hepatitis C (AHC). RAVs
      were identified using geno2pheno, and 98 concatenated NS3/NS5A alignments were
      constructed to identify transmission clusters using a maximum likelihood
      approach. RESULTS: G1a was notably more prevalent compared with G1b among men
      having-sex-with-men (MSM) (60.0% vs. 31.3%, P = 0.004), AHC cases (46.7% vs.
      25.4%, P = 0.019), and patients diagnosed with syphilis (52.2% vs. 24.5%, P =
      0.009). The overall NS3/NS5A RAVs frequency was 14.3% with variants occurring
      more often in G1a compared with G1b (27.5% vs. 5.2%, P = 0.005), mostly for NS3
      due to the high prevalence of polymorphism Q80K. NS5A RAVs were only found in
      2.9% of sequences. Significant clustering was observed for 73.5% of the Polish
      sequences, however, more common in G1a MSM compared with G1b (50.0% vs. 25.9%, P
      = 0.02). The identified clusters contained sequences originating from up to 5
      Polish cities, located within a mean distance of 370 km. CONCLUSIONS: Close
      clustering of Polish strains suggests the presence of compartmentalized epidemics
      of MSM that fuel the spread of G1a variants. Particularly patients with AHC form
      a national transmission network, including clusters enriched with the NS3 Q80K
      polymorphism.

PMID- 29337849
TI  - Vitamin E as a Treatment for Nonalcoholic Fatty Liver Disease: Reality or Myth?
AB  - Obesity is one of the major epidemics of this millennium, and its incidence is
      growing worldwide. Following the epidemics of obesity, nonalcoholic fatty liver
      disease (NAFLD) has become a disease of increasing prevalence and a leading cause
      of morbidity and mortality closely related to cardiovascular disease,
      malignancies, and cirrhosis. It is believed that oxidative stress is a main
      player in the development and progression of NAFLD. Currently, a pharmacological
      approach has become necessary in NAFLD because of a failure to modify lifestyle
      and dietary habits in most patients. Vitamin E is a potent antioxidant that has
      been shown to reduce oxidative stress in NAFLD. This review summarizes the
      biological activities of vitamin E, with a primary focus on its therapeutic
      efficacy in NAFLD.

PMID- 29337850
TI  - Rosuvastatin Improves Vaspin Serum Levels in Obese Patients with Acute Coronary
      Syndrome.
AB  - : Adipose tissue-derived serine protease inhibitor (vaspin), which has endocrine
      and local roles in atherosclerosis growth, is also synthesized by adipose tissue;
      it was found that vaspin was negatively correlated with blood pressure in obese
      patients, while vaspin levels were decreased in endothelial dysfunction. The aim
      of the present study was to determine rosuvastatin modulation effects on serum
      vaspin levels in acute coronary syndrome (ACS) with class I obesity. A total
      number of seventy patients with acute coronary syndrome previously and currently
      treated with rosuvastatin was compared to 40 patients with IHD not treated by
      rosuvastatin as a control. Vaspin serum levels were higher in rosuvastatin
      treated patients with acute coronary syndrome compared to the patients with acute
      coronary syndrome not treated by rosuvastatin, p < 0.01. Additionally, in the
      rosuvastatin-treated group, patients with STEMI showed higher vaspin serum levels
      compared to NSTEMI p < 0.01. CONCLUSION: Rosuvastatin significantly increases
      vaspin serum levels in acute coronary syndrome.

PMID- 29337851
TI  - Transcriptional Regulation by CpG Sites Methylation in the Core Promoter Region
      of the Bovine SIX1 Gene: Roles of Histone H4 and E2F2.
AB  - DNA methylation is a major epigenetic modification of the genome and has an
      essential role in muscle development. The SIX1 gene is thought to play a
      principal role in mediating skeletal muscle development. In the present study, we
      determined that bovine SIX1 expression levels were significantly higher in the
      fetal bovine group (FB) and in undifferentiated Qinchuan cattle muscle cells
      (QCMCs) than in the adult bovine group (AB) and in differentiated QCMCs.
      Moreover, a bisulfite sequencing polymerase chain reaction (BSP) analysis of DNA
      methylation levels showed that three CpG sites in the core promoter region (-216/
      28) of the bovine SIX1 gene exhibited significantly higher DNA methylation levels
      in the AB and differentiated QCMCs groups. In addition, we found that DNA
      methylation of SIX1 core promoter in vitro obviously influences the promoter
      activities. An electrophoretic mobility shift assay (EMSA) and chromatin
      immunoprecipitation (ChIP) assay, in combination with site-directed mutation and
      siRNA interference, demonstrated that histone H4 and E2F2 bind to the -216/-28
      region and play important roles in SIX1 methylation regulation during
      development. The results of this study provide the foundation for a better
      understanding of the regulation of bovine SIX1 expression via methylation and
      muscle developmental in beef cattle.

PMID- 29337852
TI  - Reference Gene Selection for Quantitative Real-Time Reverse-Transcriptase PCR in
      Annual Ryegrass (Lolium multiflorum) Subjected to Various Abiotic Stresses.
AB  - To select the most stable reference genes in annual ryegrass (Lolium
      multiflorum), we studied annual ryegrass leaf tissues exposed to various abiotic
      stresses by qRT-PCR and selected 11 candidate reference genes, i.e., 18S rRNA,
      E2, GAPDH, eIF4A, HIS3, SAMDC, TBP-1, Unigene71, Unigene77, Unigene755, and
      Unigene14912. We then used GeNorm, NormFinder, and BestKeeper to analyze the
      expression stability of these 11 genes, and used RefFinder to comprehensively
      rank genes according to stability. Under different stress conditions, the most
      suitable reference genes for studies of leaf tissues of annual ryegrass were
      different. The expression of the eIF4A gene was the most stable under drought
      stress. Under saline-alkali stress, Unigene14912 has the highest expression
      stability. Under acidic aluminum stress, SAMDC expression stability was highest.
      Under heavy metal stress, Unigene71 expression had the highest stability.
      According to the software analyses, Unigene14912, HIS3, and eIF4A were the most
      suitable for analyses of abiotic stress in tissues of annual ryegrass. GAPDH was
      the least suitable reference gene. In conclusion, selecting appropriate reference
      genes under abiotic stress not only improves the accuracy of annual ryegrass gene
      expression analyses, but also provides a theoretical reference for the
      development of reference genes in plants of the genus Lolium.

PMID- 29337853
TI  - Specific Molecular Signatures for Type II Crustins in Penaeid Shrimp Uncovered by
      the Identification of Crustin-Like Antimicrobial Peptides in Litopenaeus
      vannamei.
AB  - Crustins form a large family of antimicrobial peptides (AMPs) in crustaceans
      composed of four sub-groups (Types I-IV). Type II crustins (Type IIa or
      "Crustins" and Type IIb or "Crustin-like") possess a typical hydrophobic N
      terminal region and are by far the most representative sub-group found in penaeid
      shrimp. To gain insight into the molecular diversity of Type II crustins in
      penaeids, we identified and characterized a Type IIb crustin in Litopenaeus
      vannamei (Crustin-like Lv) and compared Type II crustins at both molecular and
      transcriptional levels. Although L. vannamei Type II crustins (Crustin Lv and
      Crustin-like Lv) are encoded by separate genes, they showed a similar tissue
      distribution (hemocytes and gills) and transcriptional response to the shrimp
      pathogens Vibrio harveyi and White spot syndrome virus (WSSV). As Crustin Lv,
      Crustin-like Lv transcripts were found to be present early in development,
      suggesting a maternal contribution to shrimp progeny. Altogether, our in silico
      and transcriptional data allowed to conclude that (1) each sub-type displays a
      specific amino acid signature at the C-terminal end holding both the cysteine
      rich region and the whey acidic protein (WAP) domain, and that (2) shrimp Type II
      crustins evolved from a common ancestral gene that conserved a similar pattern of
      transcriptional regulation.

PMID- 29337854
TI  - Announcing the 2018 Medicines Travel Award for PostDocs.
AB  - For the Medicines Travel Award 2018, we received a total of 41 applications from
      all over the world, of a wery high quality[...].

PMID- 29337856
TI  - Interaction between Hepatitis B Virus and Toll-Like Receptors: Current Status and
      Potential Therapeutic Use for Chronic Hepatitis B.
AB  - Immune defense against infection with the hepatitis B virus (HBV) is complex and
      involves both host innate and adaptive immune systems. It is well accepted that
      the development of sufficient HBV-specific T cell and B cell responses are
      required for controlling an HBV infection. However, the contribution of innate
      immunity to removing HBV has been explored in recent years. Toll-like receptors
      (TLRs) are recognized as the first line of antiviral immunity because they
      initiate intracellular signaling pathways to induce antiviral mediators such as
      interferons (IFNs) and other cytokines. Recent studies show that the activation
      of TLR-mediated signaling pathways results in a suppression of HBV replication in
      vitro and in vivo. However, HBV has also evolved strategies to counter TLR
      responses including the suppression of TLR expression and the blockage of
      downstream signaling pathways. Antiviral treatment in chronic HBV-infected
      patients leads to an upregulation of TLR expression and the restoration of its
      innate antiviral functions. Thus, TLR activation may serve as an additional
      immunotherapeutic option for treating chronic HBV infection in combination with
      antiviral treatment.

PMID- 29337858
TI  - Investigation on the Effect of a Pre-Center Drill Hole and Tool Material on
      Thrust Force, Surface Roughness, and Cylindricity in the Drilling of Al7075.
AB  - Drilling is one of the most useful metal cutting processes and is used in various
      applications, such as aerospace, electronics, and automotive. In traditional
      drilling methods, the thrust force, torque, tolerance, and tribology (surface
      roughness) are related to the cutting condition and tool geometry. In this paper,
      the effects of a pre-center drill hole, tool material, and drilling strategy
      (including continuous and non-continuous feed) on thrust force, surface
      roughness, and dimensional accuracy (cylindricity) have been investigated. The
      results show that using pre-center drill holes leads to a reduction of the
      engagement force and an improvement in the surface quality and cylindricity. Non
      continuous drilling reduces the average thrust force and cylindricity value, and
      High Speed Steels HSS-Mo (high steel speed + 5-8% Mo) reduces the maximum
      quantity of cutting forces. Moreover, cylindricity is directly related to cutting
      temperature and is improved by using a non-continuous drilling strategy.

PMID- 29337857
TI  - Low Molecular Weight Chitosan-Insulin Complexes Solubilized in a Mixture of Self
      Assembled Labrosol and Plurol Oleaque and Their Glucose Reduction Activity in
      Rats.
AB  - Oral insulin delivery that better mimics physiological pathways is a necessity as
      it ensures patient comfort and compliance. A system which is based on a vehicle
      of nano order where positively charged chitosan interacts with negatively charged
      insulin and forms a polyelectrolyte complex (PEC) solubilizate, which is then
      solubilized into an oily phase of oleic acid, labrasol, and plurol oleaque
      protects insulin against enzymatic gastrointestinal reduction. The use of an
      anionic fatty acid in the oily phase, such as oleic acid, is thought to allow an
      interaction with cationic chitosan, hence reducing particle size. Formulations
      were assessed based on their hypoglycaemic capacities in diabetic rats as
      compared to conventional subcutaneous dosage forms. 50 IU/kg oral insulin
      strength could only induce blood glucose reduction equivalent to that of 5 IU/kg
      (1 International unit = 0.0347 mg of human insulin). Parameters that influence
      the pharmacological availability were evaluated. A preliminary investigation of
      the mechanism of absorption suggests the involvement of the lymphatic route.

PMID- 29337859
TI  - Effects of Pharmacists' Interventions on Inappropriate Drug Use and Drug-Related
      Readmissions in People with Dementia-A Secondary Analysis of a Randomized
      Controlled Trial.
AB  - Age-associated physiological changes and extensive drug treatment including use
      of potentially inappropriate medications (PIMs) pose a significant risk of drug
      drug interactions and adverse drug events among elderly people with dementia.
      This study aimed at analysing the effects of clinical pharmacists' interventions
      on use of PIMs, risk of emergency department visits, and time to
      institutionalization. Furthermore, a descriptive analysis was conducted of
      circumstances associated with drug-related readmissions. This is a secondary
      analysis of data from a randomized controlled intervention study conducted in two
      hospitals in Northern Sweden. The study included patients (n = 460) 65 years or
      older with dementia or cognitive impairment. The intervention consisted of
      comprehensive medication reviews conducted by clinical pharmacists as part of a
      healthcare team. There was a larger decrease in PIMs in the intervention group
      compared with the control group (p = 0.011). No significant difference was found
      in time to first all-cause emergency department visits (HR = 0.994, 95% CI =
      0.755-1.307 p = 0.963, simple Cox regression) or time to institutionalization (HR
      = 0.761, 95% CI = 0.409-1.416 p = 0.389, simple Cox regression) within 180 days.
      Common reasons for drug-related readmissions were negative effects of sedatives,
      opioids, antidepressants, and anticholinergic agents, resulting in confusion,
      falling, and sedation. Drug-related readmissions were associated with living at
      home, heart failure, and diabetes. Pharmacist-provided interventions were able to
      reduce PIMs among elderly people with dementia and cognitive impairment.

PMID- 29337860
TI  - Reporting and Handling of Indeterminate Bone Scan Results in the Staging of
      Prostate Cancer: A Systematic Review.
AB  - Bone scintigraphy is key in imaging skeletal metastases in newly diagnosed
      prostate cancer. Unfortunately, a notable proportion of scans are not readily
      classified as positive or negative but deemed indeterminate. The extent of
      reporting of indeterminate bone scans and how such scans are handled in clinical
      trials are not known. A systematic review was conducted using electronic
      databases up to October 2016. The main outcome of interest was the reporting of
      indeterminate bone scans, analyses of how such scans were managed, and
      exploratory analyses of the association of study characteristics and the
      reporting of indeterminate bone scan results. Seventy-four eligible clinical
      trials were identified. The trials were mostly retrospective (85%), observational
      (95%), large trials (median 195 patients) from five continents published over
      four decades. The majority of studies had university affiliation (72%), and an
      author with imaging background (685). Forty-five studies (61%) reported an
      indeterminate option for the bone scan and 23 studies reported the proportion of
      indeterminate scans (median 11.4%). Most trials (44/45, 98%) reported how to
      handle indeterminate scans. Most trials (n = 39) used add-on supplementary
      imaging, follow-up bone scans, or both. Exploratory analyses showed a significant
      association of reporting of indeterminate results and number of patients in the
      study (p = 0.024) but failed to reach statistical significance with other
      variables tested. Indeterminate bone scan for staging of prostate cancer was
      insufficiently reported in clinical trials. In the case of indeterminate scans,
      most studies provided adequate measures to obtain the final status of the
      patients.

PMID- 29337861
TI  - Protein from Meat or Vegetable Sources in Meals Matched for Fiber Content has
      Similar Effects on Subjective Appetite Sensations and Energy Intake-A Randomized
      Acute Cross-Over Meal Test Study.
AB  - Higher-protein meals decrease hunger and increase satiety compared to lower
      protein meals. However, no consensus exists about the different effects of animal
      and vegetable proteins on appetite. We investigated how a meal based on vegetable
      protein (fava beans/split peas) affected ad libitum energy intake and appetite
      sensations, compared to macronutrient-balanced, iso-caloric meals based on animal
      protein (veal/pork or eggs). Thirty-five healthy men were enrolled in this acute
      cross-over study. On each test day, participants were presented with one of four
      test meals (~3550 kilojoules (kJ) 19% of energy from protein), based on fava
      beans/split peas (28.5 g fiber), pork/veal or eggs supplemented with pea fiber to
      control for fiber content (28.5 g fiber), or eggs without supplementation of
      fiber (6.0 g fiber). Subjective appetite sensations were recorded at baseline and
      every half hour until the ad libitum meal three hours later. There were no
      differences in ad libitum energy intake across test meals (p > 0.05). Further, no
      differences were found across meals for hunger, satiety, fullness, prospective
      food consumption, or composite appetite score (all p > 0.05). Iso-caloric,
      macronutrient-balanced, fiber-matched meals based on vegetable protein (fava
      beans/split peas) or animal protein (veal/pork or eggs) had similar effects on ad
      libitum energy intake and appetite sensations.

PMID- 29337862
TI  - Therapeutic Management of Pseudomonas aeruginosa Bloodstream Infection Non
      Susceptible to Carbapenems but Susceptible to "Old" Cephalosporins and/or to
      Penicillins.
AB  - It is unknown as to whether other beta-lactams can be used for bloodstream
      infections (BSI) resulting from Pseudomonas aeruginosa (PA) which are non
      susceptible to one or more carbapenem. We conducted a retrospective cohort study
      at the Assaf Harofeh Medical Center (AHMC) from January 2010 to August 2014.
      Adult patients with PA-BSI non-susceptible to a group 2 carbapenem but
      susceptible to ceftazidime or piperacillin (with or without tazobactam), were
      enrolled. We compared the outcomes of patients who received an appropriate beta
      lactam antibiotic ("cases") to those who received an appropriate non-beta-lactam
      antibiotic ("controls"). Whole genome sequencing was performed for one of the
      isolates. Twenty-six patients with PA-BSI met inclusion criteria: 18 received a
      beta-lactam and 8 a non-beta-lactam (three a fluoroquinolone, two colistin, one a
      fluoroquinolone and an aminoglycoside, one a fluoroquinolone and colistin, and
      one colistin and an aminoglycoside). All clinical outcomes were similar between
      the groups. There were large variations in the phenotypic susceptibilities of the
      strains. A detailed molecular investigation of one isolate revealed a strain that
      belonged to MLST-137, with the presence of multiple efflux pumps, OXA-50, and a
      chromosomally mediated Pseudomonas-derived cephalosporinase (PDC). The oprD gene
      was intact. Non-carbapenem-beta-lactams may still be effective alternatives for
      short duration therapy (up to 14 days) for BSI caused by a carbapenem non
      susceptible (but susceptible to ceftazidime, piperacillin, and/or piperacillin
      tazobactam) PA strain. This observation requires further confirmatory analyses.
      Future molecular investigations should be performed, in order to further analyze
      additional potential mechanisms for this prevalent phenotype.

PMID- 29337864
TI  - Effects of Chitosan-PVA and Cu Nanoparticles on the Growth and Antioxidant
      Capacity of Tomato under Saline Stress.
AB  - Chitosan is a natural polymer, which has been used in agriculture to stimulate
      crop growth. Furthermore, it has been used for the encapsulation of nanoparticles
      in order to obtain controlled release. In this work, the effect of chitosan-PVA
      and Cu nanoparticles (Cu NPs) absorbed on chitosan-PVA on growth, antioxidant
      capacity, mineral content, and saline stress in tomato plants was evaluated. The
      results show that treatments with chitosan-PVA increased tomato growth.
      Furthermore, chitosan-PVA increased the content of chlorophylls a and b, total
      chlorophylls, carotenoids, and superoxide dismutase. When chitosan-PVA was mixed
      with Cu NPs, the mechanism of enzymatic defense of tomato plants was activated.
      The chitosan-PVA and chitosan-PVA + Cu NPs increased the content of vitamin C and
      lycopene, respectively. The application of chitosan-PVA and Cu NPs might induce
      mechanisms of tolerance to salinity.

PMID- 29337863
TI  - Dairy-Related Dietary Patterns, Dietary Calcium, Body Weight and Composition: A
      Study of Obesity in Polish Mothers and Daughters, the MODAF Project.
AB  - The role of the family environment in regards to dairy products and dietary
      calcium in the context of obesity is not fully understood. The aim of the study
      was to investigate the association among dairy-related dietary patterns (DDPs),
      dietary calcium, body weight and composition in mothers and daughters. Data were
      collected through a cross-sectional survey within the MODAF Project. A total
      sample of 712 pairs of mothers (<60 years) and daughters (12-21 years) was
      studied. This study included 691 pairs. A semi-quantitative food frequency
      questionnaire (ADOS-Ca) was used to collect dietary data. Waist circumference
      (WC), body fat, waist-to-height ratio (WHtR) and body mass index (BMI) were
      determined. Previously derived DDPs were used-three in mothers and three in
      daughters. In mothers, two of the DDPs were characterized by higher consumption
      of various dairy products with suboptimal calcium content (means: 703 or 796
      mg/day) which decreased the chance of: z-WC > 1 standard deviation (SD), WC > 80
      cm, body fat > 32%, WHtR > 0.5, BMI = 25-29.9 kg/m2 or BMI >= 30 kg/m2 by 44-67%
      when compared to low-dairy low-calcium DDP (288 mg/day). In mothers per 100
      mg/day of dietary calcium, the chance of z-WC > 1SD, WC > 80 cm, z-WHtR > 1SD,
      WHtR > 0.5 cm, BMI = 25 to 29.9 kg/m2 or BMI >= 30 kg/m2 decreased by 5-9%. In
      correspondence analysis, a clear association was found between mothers' and
      daughters' low-dairy low-calcium DDPs and upper categories of z-WC (>1 SDs). This
      study reinforces evidence of the similarity between mothers and daughters in
      dairy-related dietary patterns and provides a new insight on the adverse relation
      between low-dairy low-calcium dietary patterns and obesity. It was found that
      diets containing various dairy products with suboptimal dietary calcium content
      may be recommended in obesity prevention.

PMID- 29337865
TI  - Pharmacokinetics and Drug Metabolism in Canada: The Current Landscape-A Summary
      of This Indispensable Special Issue.
AB  - Canadian Pharmaceutical Scientists have a rich history of groundbreaking research
      in pharmacokinetics and drug metabolism undertaken primarily throughout its
      Pharmacy Faculties and within the Pharmaceutical and Biotechnology
      industry.[...].

PMID- 29337867
TI  - Tensile and Creep Testing of Sanicro 25 Using Miniature Specimens.
AB  - Tensile and creep properties of new austenitic steel Sanicro 25 at room
      temperature and operating temperature 700  degrees C were investigated by testing
      on miniature specimens. The results were correlated with testing on conventional
      specimens. Very good agreement of results was obtained, namely in yield and
      ultimate strength, as well as short-term creep properties. Although the creep
      rupture time was found to be systematically shorter and creep ductility lower in
      the miniature test, the minimum creep rates were comparable. The analysis of the
      fracture surfaces revealed similar ductile fracture morphology for both specimen
      geometries. One exception was found in a small area near the miniature specimen
      edge that was cut by electro discharge machining, where an influence of the steel
      fracture behavior at elevated temperature was identified.

PMID- 29337868
TI  - Bacteriophage GC1, a Novel Tectivirus Infecting Gluconobacter Cerinus, an Acetic
      Acid Bacterium Associated with Wine-Making.
AB  - The Gluconobacter phage GC1 is a novel member of the Tectiviridae family isolated
      from a juice sample collected during dry white wine making. The bacteriophage
      infects Gluconobacter cerinus, an acetic acid bacterium which represents a
      spoilage microorganism during wine making, mainly because it is able to produce
      ethyl alcohol and transform it into acetic acid. Transmission electron microscopy
      revealed tail-less icosahedral particles with a diameter of ~78 nm. The linear
      double-stranded DNA genome of GC1 (16,523 base pairs) contains terminal inverted
      repeats and carries 36 open reading frames, only a handful of which could be
      functionally annotated. These encode for the key proteins involved in DNA
      replication (protein-primed family B DNA polymerase) as well as in virion
      structure and assembly (major capsid protein, genome packaging ATPase (adenosine
      triphosphatase) and several minor capsid proteins). GC1 is the first tectivirus
      infecting an alphaproteobacterial host and is thus far the only temperate
      tectivirus of gram-negative bacteria. Based on distinctive sequence and life
      style features, we propose that GC1 represents a new genus within the
      Tectiviridae, which we tentatively named "Gammatectivirus". Furthermore, GC1
      helps to bridge the gap in the sequence space between alphatectiviruses and
      betatectiviruses.

PMID- 29337866
TI  - CRISPR-Cas Targeting of Host Genes as an Antiviral Strategy.
AB  - Currently, a new gene editing tool-the Clustered Regularly Interspaced Short
      Palindromic Repeats (CRISPR) associated (Cas) system-is becoming a promising
      approach for genetic manipulation at the genomic level. This simple method,
      originating from the adaptive immune defense system in prokaryotes, has been
      developed and applied to antiviral research in humans. Based on the
      characteristics of virus-host interactions and the basic rules of nucleic acid
      cleavage or gene activation of the CRISPR-Cas system, it can be used to target
      both the virus genome and host factors to clear viral reservoirs and prohibit
      virus infection or replication. Here, we summarize recent progress of the CRISPR
      Cas technology in editing host genes as an antiviral strategy.

PMID- 29337869
TI  - Aquaporin Expression and Water Transport Pathways inside Leaves Are Affected by
      Nitrogen Supply through Transpiration in Rice Plants.
AB  - The photosynthetic rate increases under high-N supply, resulting in a large CO2
      transport conductance in mesophyll cells. It is less known that water movement is
      affected by nitrogen supply in leaves. This study investigated whether the
      expression of aquaporin and water transport were affected by low-N (0.7 mM) and
      high-N (7 mM) concentrations in the hydroponic culture of four rice varieties:
      (1) Shanyou 63 (SY63), a hybrid variant of the indica species; (2) Yangdao 6
      (YD6), a variant of indica species; (3) Zhendao 11 (ZD11), a hybrid variant of
      japonica species; and (4) Jiuyou 418 (JY418), another hybrid of the japonica
      species. Both the photosynthetic and transpiration rate were increased by the
      high-N supply in the four varieties. The expressions of aquaporins, plasma
      membrane intrinsic proteins (PIPs), and tonoplast membrane intrinsic protein
      (TIP) were higher in high-N than low-N leaves, except in SY63. Leaf hydraulic
      conductance (Kleaf) was lower in high-N than low-N leaves in SY63, while Kleaf
      increased under high-N supply in the YD6 variant. Negative correlations were
      observed between the expression of aquaporin and the transpiration rate in
      different varieties. Moreover, there was a significant negative correlation
      between transpiration rate and intercellular air space. In conclusion, the change
      in expression of aquaporins could affect Kleaf and transpiration. A feedback
      effect of transpiration would regulate aquaporin expression. The present results
      imply a coordination of gas exchange with leaf hydraulic conductance.

PMID- 29337870
TI  - Glioblastoma under Siege: An Overview of Current Therapeutic Strategies.
AB  - Glioblastoma is known to be one of the most lethal and untreatable human tumors.
      Surgery and radiotherapy in combination with classical alkylating agents such as
      temozolomide offer little hope to escape a poor prognosis. For these reasons,
      enormous efforts are currently devoted to refine in vivo and in vitro models with
      the specific goal of finding new molecular aberrant pathways, suitable to be
      targeted by a variety of therapeutic approaches, including novel pharmaceutical
      formulations and immunotherapy strategies. In this review, we will first discuss
      current molecular classification based on genomic and transcriptomic criteria.
      Also, the state of the art in current clinical practice for glioblastoma therapy
      in the light of the recent molecular classification, together with ongoing phases
      II and III clinical trials, will be described. Finally, new pharmaceutical
      formulations such as nanoparticles and viral vectors, together with new
      strategies entailing the use of monoclonal antibodies, vaccines and immunotherapy
      agents, such as checkpoint inhibitors, will also be discussed.

PMID- 29337871
TI  - Influence of Kartogenin on Chondrogenic Differentiation of Human Bone Marrow
      Derived MSCs in 2D Culture and in Co-Cultivation with OA Osteochondral Explant.
AB  - Articular cartilage has limited capacity for natural regeneration and repair. In
      the present study, we evaluated kartogenin (KGN), a bioactive small heterocyclic
      molecule, for its effect on in vitro proliferation and chondrogenic
      differentiation of human bone marrow-derived mesenchymal stromal cells (hBMSCs)
      in monolayer culture and in co-culture models in vitro. OA osteochondral
      cylinders and hBMSCs were collected during total knee replacement. The effect of
      KGN on hBMSCs during 21 days of culture was monitored by real-time proliferation
      assay, immunofluorescence staining, histological assay, scanning electron
      microscopy (SEM) (imaging and multiplex enzyme-linked immunosorbent assay) ELISA
      assay. The rate of proliferation of hBMSCs was significantly increased by
      treatment with 10 uM KGN during nine days of culture. Histological and SEM
      analyses showed the ability of hBMSCs in the presence of KGN to colonize the
      surface of OA cartilage and to produce glycosaminoglycans and proteoglycans after
      21 days of co-culture. KGN treated hBMSCs secreted higher concentrations of TIMPs
      and the secretion of pro-inflammatory molecules (MMP 13, TNF-alpha) were
      significantly suppressed in comparison with control without hBMSCs. Our
      preliminary results support the concept that 10 uM KGN enhances proliferation and
      chondrogenic differentiation of hBMSCs and suggest that KGN is a potential
      promoter for cell-based therapeutic application for cartilage regeneration.

PMID- 29337872
TI  - Mutation Analysis in Cultured Cells of Transgenic Rodents.
AB  - To comply with guiding principles for the ethical use of animals for experimental
      research, the field of mutation research has witnessed a shift of interest from
      large-scale in vivo animal experiments to small-sized in vitro studies. Mutation
      assays in cultured cells of transgenic rodents constitute, in many ways, viable
      alternatives to in vivo mutagenicity experiments in the corresponding animals. A
      variety of transgenic rodent cell culture models and mutation detection systems
      have been developed for mutagenicity testing of carcinogens. Of these, transgenic
      Big Blue(r) (Stratagene Corp., La Jolla, CA, USA, acquired by Agilent
      Technologies Inc., Santa Clara, CA, USA, BioReliance/Sigma-Aldrich Corp.,
      Darmstadt, Germany) mouse embryonic fibroblasts and the lambda Select cII
      Mutation Detection System have been used by many research groups to investigate
      the mutagenic effects of a wide range of chemical and/or physical carcinogens.
      Here, we review techniques and principles involved in preparation and culturing
      of Big Blue(r) mouse embryonic fibroblasts, treatment in vitro with
      chemical/physical agent(s) of interest, determination of the cII mutant frequency
      by the lambda Select cII assay and establishment of the mutation spectrum by DNA
      sequencing. We describe various approaches for data analysis and interpretation
      of the results. Furthermore, we highlight representative studies in which the Big
      Blue(r) mouse cell culture model and the lambda Select cII assay have been used
      for mutagenicity testing of diverse carcinogens. We delineate the advantages of
      this approach and discuss its limitations, while underscoring auxiliary methods,
      where applicable.

PMID- 29337873
TI  - Two Novel Proline-Containing Catechin Glucoside from Water-Soluble Extract of
      Codonopsis pilosula.
AB  - Choushenflavonoids A (1) and B (2), two unusual proline-containing catechin
      glucosides, were isolated from the roots of Codonopsis pilosula cultivated in a
      high-altitude location of Yunnan province. Their structures were determined by
      spectroscopic data and chemical methods. Specifically, the absolute configuration
      of glucose residue in 1 and 2 was assigned by acid hydrolysis followed by
      derivatization and gas chromatography (GC) analysis. In addition, biological
      evaluation of 1 and 2 against Sirtuin 1 (SIRT1) was carried out.

PMID- 29337874
TI  - Angular Molecular-Electronic Sensor with Negative Magnetohydrodynamic Feedback.
AB  - A high-precision angular accelerometer based on molecular-electronic transfer
      (MET) technology with a high dynamic range and a low level of self-noise has been
      developed. Its difference from the analogues is in the use of liquid
      (electrolyte) as the inertial mass and the use of negative feedback based on the
      magnetohydrodynamic effect. This article reports on the development of the
      angular molecular-electronic accelerometer with a magnetohydrodynamic cell for
      the creation of negative feedback, and the optimization of electronics for the
      creation of a feedback signal. The main characteristics of the angular
      accelerometer, such as amplitude-frequency characteristics, self-noise and Allan
      variance were experimentally measured. The obtained output parameters were
      compared to its analogues and it showed perspectives for further development in
      this field.

PMID- 29337877
TI  - Virtual Environments for Visualizing Structural Health Monitoring Sensor
      Networks, Data, and Metadata.
AB  - Visualization of sensor networks, data, and metadata is becoming one of the most
      pivotal aspects of the structural health monitoring (SHM) process. Without the
      ability to communicate efficiently and effectively between disparate groups
      working on a project, an SHM system can be underused, misunderstood, or even
      abandoned. For this reason, this work seeks to evaluate visualization techniques
      in the field, identify flaws in current practices, and devise a new method for
      visualizing and accessing SHM data and metadata in 3D. More precisely, the work
      presented here reflects a method and digital workflow for integrating SHM sensor
      networks, data, and metadata into a virtual reality environment by combining
      spherical imaging and informational modeling. Both intuitive and interactive,
      this method fosters communication on a project enabling diverse practitioners of
      SHM to efficiently consult and use the sensor networks, data, and metadata. The
      method is presented through its implementation on a case study, Streicker Bridge
      at Princeton University campus. To illustrate the efficiency of the new method,
      the time and data file size were compared to other potential methods used for
      visualizing and accessing SHM sensor networks, data, and metadata in 3D.
      Additionally, feedback from civil engineering students familiar with SHM is used
      for validation. Recommendations on how different groups working together on an
      SHM project can create SHM virtual environment and convey data to proper
      audiences, are also included.

PMID- 29337876
TI  - Microenvironment Stimuli HGF and Hypoxia Differently Affected miR-125b and Ets-1
      Function with Opposite Effects on the Invasiveness of Bone Metastatic Cells: A
      Comparison with Breast Carcinoma Cells.
AB  - We examined the influence of microenvironment stimuli on molecular events
      relevant to the biological functions of 1833-bone metastatic clone and the
      parental MDA-MB231 cells. (i) In both the cell lines, hepatocyte growth factor
      (HGF) and the osteoblasts' biological products down regulated nuclear Ets-1
      protein level in concomitance with endogenous miR-125b accumulation. In contrast,
      under hypoxia nuclear Ets-1 was unchanged, notwithstanding the miR-125b increase.
      (ii) Also, the 1833-cell invasiveness and the expression of Endothelin-1, the
      target gene of Ets-1/HIF-1, showed opposite patterns under HGF and hypoxia. We
      clarified the molecular mechanism(s) reproducing the high miR-125b levels with
      the mimic in 1833 cells. Under hypoxia, the miR-125b mimic maintained a basal
      level and functional Ets-1 protein, as testified by the elevated cell
      invasiveness. However, under HGF ectopic miR-125b downregulated Ets-1 protein and
      cell motility, likely involving an Ets-1-dominant negative form sensible to serum
      conditions; Ets-1-activity inhibition by HGF implicated HIF-1alpha accumulation,
      which drugged Ets-1 in the complex bound to the Endothelin-1 promoter.
      Altogether, 1833-cell exposure to HGF would decrease Endothelin-1 transactivation
      and protein expression, with the possible impairment of Endothelin-1-dependent
      induction of E-cadherin, and the reversion towards an invasive phenotype: this
      was favoured by Ets-1 overexpression, which inhibited HIF-1alpha expression and
      HIF-1 activity. (iii) In MDA-MB231 cells, HGF strongly and rapidly decreased Ets
      1, hampering invasiveness and reducing Ets-1-binding to Endothelin-1 promoter;
      HIF-1alpha did not form a complex with Ets-1 and Endothelin-1-luciferase activity
      was unchanged. Overall, depending on the microenvironment conditions and
      endogenous miR-125b levels, bone-metastatic cells might switch from Ets-1
      dependent motility towards colonization/growth, regulated by the balance between
      Ets-1 and HIF-1.

PMID- 29337875
TI  - Aux/IAA Gene Family in Plants: Molecular Structure, Regulation, and Function.
AB  - Auxin plays a crucial role in the diverse cellular and developmental responses of
      plants across their lifespan. Plants can quickly sense and respond to changes in
      auxin levels, and these responses involve several major classes of auxin
      responsive genes, including the Auxin/Indole-3-Acetic Acid (Aux/IAA) family, the
      auxin response factor (ARF) family, small auxin upregulated RNA (SAUR), and the
      auxin-responsive Gretchen Hagen3 (GH3) family. Aux/IAA proteins are short-lived
      nuclear proteins comprising several highly conserved domains that are encoded by
      the auxin early response gene family. These proteins have specific domains that
      interact with ARFs and inhibit the transcription of genes activated by ARFs.
      Molecular studies have revealed that Aux/IAA family members can form diverse
      dimers with ARFs to regulate genes in various ways. Functional analyses of
      Aux/IAA family members have indicated that they have various roles in plant
      development, such as root development, shoot growth, and fruit ripening. In this
      review, recently discovered details regarding the molecular characteristics,
      regulation, and protein-protein interactions of the Aux/IAA proteins are
      discussed. These details provide new insights into the molecular basis of the
      Aux/IAA protein functions in plant developmental processes.

PMID- 29337878
TI  - Tetrasubstituted Imidazolium Salts as Potent Antiparasitic Agents against African
      and American Trypanosomiases.
AB  - Imidazolium salts are privileged compounds in organic chemistry, and have
      valuable biological properties. Recent studies show that symmetric imidazolium
      salts with bulky moieties can display antiparasitic activity against T. cruzi.
      After developing a facile methodology for the synthesis of tetrasubstituted
      imidazolium salts from propargylamines and isocyanides, we screened a small
      library of these adducts against the causative agents of African and American
      trypanosomiases. These compounds display nanomolar activity against T. brucei and
      low (or sub) micromolar activity against T. cruzi, with excellent selectivity
      indexes and favorable molecular properties, thereby emerging as promising hits
      for the treatment of Chagas disease and sleeping sickness.

PMID- 29337879
TI  - Microwave Backscatter-Based Wireless Temperature Sensor Fabricated by an Alumina
      Backed Au Slot Radiation Patch.
AB  - A wireless and passive temperature sensor operating up to 800  degrees C is
      proposed. The sensor is based on microwave backscatter RFID (radio frequency
      identification) technology. A thin-film planar structure and simple working
      principle make the sensor easy to operate under high temperature. In this paper,
      the proposed high temperature sensor was designed, fabricated, and characterized.
      Here the 99% alumina ceramic with a dimension of 40 mm * 40 mm * 1 mm was
      prepared in micromechanics for fabrication of the sensor substrate. The
      metallization of the Au slot patch was realized in magnetron sputtering with a
      slot width of 2 mm and a slot length of 32 mm. The measured resonant frequency of
      the sensor at 25  degrees C is 2.31 GHz. It was concluded that the resonant
      frequency decreases with the increase in the temperature in range of 25-800 
      degrees C. It was shown that the average sensor sensitivity is 101.94 kHz/
      degrees C.

PMID- 29337881
TI  - Effects of Polypropylene Orientation on Mechanical and Heat Seal Properties of
      Polymer-Aluminum-Polymer Composite Films for Pouch Lithium-Ion Batteries.
AB  - In this study, polyamide-aluminum foil-polypropylene (PA-Al-PP) composite films
      with different orientation status of the PP layer were prepared, and their
      morphology, tensile, peeling and heat seal behavior were studied. The comparative
      study of tensile and fracture behaviors of single-layer film of PA, Al and PP, as
      well as the composite films of PA-Al, PP-Al and PA-Al-PP revealed that in PA-Al
      PP composite film, the PA layer with the highest tensile strength can share the
      tensile stress from the Al layer during stretching, while the PP layer with the
      lowest tensile strength can prevent further development of the small cracks on
      boundary of the Al layer during stretching. Moreover, the study of heat seal
      behavior suggested that both the orientation status and the heat seal conditions
      were important factors in determining the heat seal strength (HSS) and failure
      behavior of the sample. Four failure types were observed, and a clear
      correspondence between HSS and failure types was found. The results also
      elucidated that for the composite film, only in the cases where the tensile
      stress was efficiently released by each layer during HSS measurement could the
      composite film exhibit desired high HSS that was even higher than its tensile
      strength.

PMID- 29337880
TI  - The Sodium and Potassium Content of the Most Commonly Available Street Foods in
      Tajikistan and Kyrgyzstan in the Context of the FEEDCities Project.
AB  - This cross-sectional study is aimed at assessing sodium (Na) and potassium (K)
      content and the molar Na:K ratios of the most commonly available ready-to-eat
      street foods in Tajikistan and Kyrgyzstan. Four different samples of each of
      these foods were collected and 62 food categories were evaluated through
      bromatological analysis. Flame photometry was used to quantify sodium and
      potassium concentrations. The results show that home-made foods can be important
      sources of sodium. In particular, main dishes and sandwiches, respectively,
      contain more than 1400 and nearly 1000 mg Na in an average serving and provide
      approximately 70% and 50% of the maximum daily recommended values. Wide ranges of
      sodium content were found between individual samples of the same home-made food
      collected from different vending sites from both countries. In industrial foods,
      sodium contents ranged from 1 to 1511 mg/serving in Tajikistan, and from 19 to
      658 mg/serving in Kyrgyzstan. Most Na:K ratios exceeded the recommended level of
      1.0 and the highest ratios were found in home-made snacks (21.2) from Tajikistan
      and industrial beverages (16.4) from Kyrgyzstan. These findings not only improve
      data on the nutritional composition of foods in these countries, but may also
      serve as baseline information for future policies and interventions.

PMID- 29337883
TI  - Problematic Smartphone Use: Investigating Contemporary Experiences Using a
      Convergent Design.
AB  - Internet-enabled smartphones are increasingly ubiquitous in the Western world.
      Research suggests a number of problems can result from mobile phone overuse,
      including dependence, dangerous and prohibited use. For over a decade, this has
      been measured by the Problematic Mobile Phone Use Questionnaire (PMPU-Q). Given
      the rapid developments in mobile technologies, changes of use patterns and
      possible problematic and addictive use, the aim of the present study was to
      investigate and validate an updated contemporary version of the PMPU-Q (PMPU-Q
      R). A mixed methods convergent design was employed, including a psychometric
      survey (N = 512) alongside qualitative focus groups (N = 21), to elicit
      experiences and perceptions of problematic smartphone use. The results suggest
      the PMPU-Q-R factor structure can be updated to include smartphone dependence,
      dangerous driving, and antisocial smartphone use factors. Theories of problematic
      mobile phone use require consideration of the ubiquity and indispensability of
      smartphones in the present day and age, particularly regarding use whilst driving
      and in social interactions.

PMID- 29337882
TI  - Functional Analysis of Promoters from Three Subtypes of the PI3K Family and Their
      Roles in the Regulation of Lipid Metabolism by Insulin in Yellow Catfish
      Pelteobagrus fulvidraco.
AB  - In the present study, the length of 360, 1848 and 367 bp sequences of promoters
      from three subtypes of PI3K family (PI3KCa, PI3KC2b and PI3KC3) of yellow catfish
      Pelteobagrus fulvidraco were cloned and characterized. Bioinformatics analysis
      revealed that PI3KCa, PI3KC2b and PI3KC3 had different structures in their core
      promoter regions. The promoter regions of PI3KCa and PI3KC2b had CpG islands but
      no CAAT and TATA box. In contrast, the promoter of PI3KC3 had the canonical TATA
      and CAAT box but no CpG island. The binding sites of several transcription
      factors, such as HNF1, STAT and NF-kappaB, were predicted on PI3KCa promoter. The
      binding sites of transcription factors, such as FOXO1, PPAR-RXR, STAT, IK1, HNF6
      and HNF3, were predicted on PI3KC2b promoter and the binding sites of FOXO1 and
      STAT transcription factors were predicted on PI3KC3 promoter. Deletion analysis
      indicated that these transcriptional factors were the potential regulators to
      mediate the activities of their promoters. Subsequent mutation analysis and
      electrophoretic mobility-shift assay (EMSA) demonstrated that HNF1 and IK1
      directly bound with PI3KCa and PI3KC2b promoters and negatively regulated the
      activities of PI3KCa and PI3KC2b promoters, respectively. Conversely, FOXO1
      directly bound with the PI3KC2b and PI3KC3 promoters and positively regulated
      their promoter activities. In addition, AS1842856 (AS, a potential FOXO1
      inhibitor) incubation significantly reduced the relative luciferase activities of
      several plasmids of PI3KC2b and PI3KC3 but did not significantly influence the
      relative luciferase activities of the PI3KCa plasmids. Moreover, by using primary
      hepatocytes from yellow catfish, AS incubation significantly down-regulated the
      mRNA levels of PI3KCa, PI3KC2b and PI3KC3 and reduced triacylglyceride (TG)
      accumulation and insulin-induced TG accumulation, as well as the activities and
      the mRNA levels of several genes involved in lipid metabolism. Thus, the present
      study offers new insights into the mechanisms for transcriptional regulation of
      PI3Ks and for PI3Ks-mediated regulation of lipid metabolism by insulin in fish.

PMID- 29337884
TI  - Monitoring Strategies of Earth Dams by Ground-Based Radar Interferometry: How to
      Extract Useful Information for Seismic Risk Assessment.
AB  - The aim of this paper is to describe how ground-based radar interferometry can
      provide displacement measurements of earth dam surfaces and of vibration
      frequencies of its main concrete infrastructures. In many cases, dams were built
      many decades ago and, at that time, were not equipped with in situ sensors
      embedded in the structure when they were built. Earth dams have scattering
      properties similar to landslides for which the Ground-Based Synthetic Aperture
      Radar (GBSAR) technique has been so far extensively applied to study ground
      displacements. In this work, SAR and Real Aperture Radar (RAR) configurations are
      used for the measurement of earth dam surface displacements and vibration
      frequencies of concrete structures, respectively. A methodology for the
      acquisition of SAR data and the rendering of results is described. The
      geometrical correction factor, needed to transform the Line-of-Sight (LoS)
      displacement measurements of GBSAR into an estimate of the horizontal
      displacement vector of the dam surface, is derived. Furthermore, a methodology
      for the acquisition of RAR data and the representation of displacement temporal
      profiles and vibration frequency spectra of dam concrete structures is presented.
      For this study a Ku-band ground-based radar, equipped with horn antennas having
      different radiation patterns, has been used. Four case studies, using different
      radar acquisition strategies specifically developed for the monitoring of earth
      dams, are examined. The results of this work show the information that a Ku-band
      ground-based radar can provide to structural engineers for a non-destructive
      seismic assessment of earth dams.

PMID- 29337885
TI  - Research on Geometric Calibration of Spaceborne Linear Array Whiskbroom Camera.
AB  - The geometric calibration of a spaceborne thermal-infrared camera with a high
      spatial resolution and wide coverage can set benchmarks for providing an accurate
      geographical coordinate for the retrieval of land surface temperature. The
      practice of using linear array whiskbroom Charge-Coupled Device (CCD) arrays to
      image the Earth can help get thermal-infrared images of a large breadth with high
      spatial resolutions. Focusing on the whiskbroom characteristics of equal time
      intervals and unequal angles, the present study proposes a spaceborne linear
      array-scanning imaging geometric model, whilst calibrating temporal system
      parameters and whiskbroom angle parameters. With the help of the YG-14-China's
      first satellite equipped with thermal-infrared cameras of high spatial resolution
      China's Anyang Imaging and Taiyuan Imaging are used to conduct an experiment of
      geometric calibration and a verification test, respectively. Results have shown
      that the plane positioning accuracy without ground control points (GCPs) is
      better than 30 pixels and the plane positioning accuracy with GCPs is better than
      1 pixel.

PMID- 29337886
TI  - Mechanical Activation of Adipose Tissue and Derived Mesenchymal Stem Cells: Novel
      Anti-Inflammatory Properties.
AB  - The adipose tissue is a source of inflammatory proteins, such as TNF, IL-6, and
      CXCL8. Most of their production occurs in macrophages that act as scavengers of
      dying adipocytes. The application of an orbital mechanical force for 6-10 min at
      97 g to the adipose tissue, lipoaspirated and treated according to Coleman
      procedures, abolishes the expression of TNF-alpha and stimulates the expression
      of the anti-inflammatory protein TNF-stimulated gene-6 (TSG-6). This protein had
      protective and anti-inflammatory effects when applied to animal models of
      rheumatic diseases. We examined biopsy, lipoaspirate, and mechanically activated
      fat and observed that in addition to the increased TSG-6, Sox2, Nanog, and Oct4
      were also strongly augmented by mechanical activation, suggesting an effect on
      stromal cell stemness. Human adipose tissue-derived mesenchymal stem cells
      (hADSCs), produced from activated fat, grow and differentiate normally with
      proper cell surface markers and chromosomal integrity, but their anti
      inflammatory action is far superior compared to those mesenchymal stem cells
      (MSCs) obtained from lipoaspirate. The expression and release of inflammatory
      cytokines from THP-1 cells was totally abolished in mechanically activated
      adipose tissue-derived hADSCs. In conclusion, we report that the orbital shaking
      of adipose tissue enhances its anti-inflammatory properties, and derived MSCs
      maintain such enhanced activity.

PMID- 29337887
TI  - The Use of Municipal Solid Waste Incineration Ash in Various Building Materials:
      A Belgian Point of View.
AB  - Huge amounts of waste are being generated, and even though the incineration
      process reduces the mass and volume of waste to a large extent, massive amounts
      of residues still remain. On average, out of 1.3 billion tons of municipal solid
      wastes generated per year, around 130 and 2.1 million tons are incinerated in the
      world and in Belgium, respectively. Around 400 kT of bottom ash residues are
      generated in Flanders, out of which only 102 kT are utilized here, and the rest
      is exported or landfilled due to non-conformity to environmental regulations.
      Landfilling makes the valuable resources in the residues unavailable and results
      in more primary raw materials being used, increasing mining and related hazards.
      Identifying and employing the right pre-treatment technique for the highest value
      application is the key to attaining a circular economy. We reviewed the present
      pre-treatment and utilization scenarios in Belgium, and the advancements in
      research around the world for realization of maximum utilization are reported in
      this paper. Uses of the material in the cement industry as a binder and cement
      raw meal replacement are identified as possible effective utilization options for
      large quantities of bottom ash. Pre-treatment techniques that could facilitate
      this use are also discussed. With all the research evidence available, there is
      now a need for combined efforts from incineration and the cement industry for
      technical and economic optimization of the process flow.

PMID- 29337888
TI  - Depression Symptom Patterns and Social Correlates among Chinese Americans.
AB  - The aim of this study is to examine and compare the depression symptoms pattern
      and social correlates in three groups: foreign-born Chinese Americans, US-born
      Chinese Americans, and non-Hispanic whites. This study used data from the
      Collaborative Psychiatric Epidemiology Surveys (CPES). The study sample consists
      of 599 Chinese Americans (468 for the foreign-born and 121 for the US-born) and
      4032 non-Hispanic whites. Factor analysis was used to examine the depression
      symptom patterns by each subgroup. Four depression symptoms dimensions were
      examined: negative affect, somatic symptoms, cognitive symptoms, and suicidality.
      Logistic regression was used to investigate the effects of sociodemographic (age,
      gender, marital status, and education), physical health condition, and social
      relational factors (supports from and conflict with family and friends) on
      specific types of depression symptoms separately for the three subgroups. The
      findings showed little differences in depression symptom patterns but clear
      variation in the social correlates to the four depression dimensions across the
      three ethnocultural groups, foreign-born Chinese Americans, US-born Chinese
      Americans, and non-Hispanic whites. Clinicians should take into account the
      sociocultural factors of patients when making diagnosis and suggesting
      treatments. In addition, psychiatrists, psychologists, or other mental health
      service providers should offer treatment and coping suggestions based on the
      specific symptom dimensions of patients, and patients' ethnocultural backgrounds.

PMID- 29337890
TI  - Subcellular Reactive Oxygen Species (ROS) in Cardiovascular Pathophysiology.
AB  - There exist two opposing perspectives regarding reactive oxygen species (ROS) and
      their roles in angiogenesis and cardiovascular system, one that favors harmful
      and causal effects of ROS, while the other supports beneficial effects. Recent
      studies have shown that interaction between ROS in different sub-cellular
      compartments plays a crucial role in determining the outcomes (beneficial vs.
      deleterious) of ROS exposures on the vascular system. Oxidant radicals in one
      cellular organelle can affect the ROS content and function in other sub-cellular
      compartments in endothelial cells (ECs). In this review, we will focus on a
      critical fact that the effects or the final phenotypic outcome of ROS exposure to
      EC are tissue- or organ-specific, and depend on the spatial (subcellular
      localization) and temporal (duration of ROS exposure) modulation of ROS levels.

PMID- 29337891
TI  - Modeling of Dynamic Behavior of Carbon Fiber-Reinforced Polymer (CFRP) Composite
      under X-ray Radiation.
AB  - Carbon fiber-reinforced polymer (CFRP) composites have been increasingly used in
      spacecraft applications. Spacecraft may encounter highenergy-density X-ray
      radiation in outer space that can cause severe damage. To protect spacecraft from
      such unexpected damage, it is essential to predict the dynamic behavior of CFRP
      composites under X-ray radiation. In this study, we developed an in-house three
      dimensional explicit finite element (FEM) code to investigate the dynamic
      responses of CFRP composite under X-ray radiation for the first time, by
      incorporating a modified PUFF equation-of-state. First, the blow-off impulse
      (BOI) momentum of an aluminum panel was predicted by our FEM code and compared
      with an existing radiation experiment. Then, the FEM code was utilized to
      determine the dynamic behavior of a CFRP composite under various radiation
      conditions. It was found that the numerical result was comparable with the
      experimental one. Furthermore, the CFRP composite was more effective than the
      aluminum panel in reducing radiation-induced pressure and BOI momentum. The
      numerical results also revealed that a 1 keV X-ray led to vaporization of surface
      materials and a high-magnitude compressive stress wave, whereas a low-magnitude
      stress wave was generated with no surface vaporization when a 3 keV X-ray was
      applied.

PMID- 29337892
TI  - Improving Remote Health Monitoring: A Low-Complexity ECG Compression Approach.
AB  - Recent advances in mobile technology have created a shift towards using battery
      driven devices in remote monitoring settings and smart homes. Clinicians are
      carrying out diagnostic and screening procedures based on the electrocardiogram
      (ECG) signals collected remotely for outpatients who need continuous monitoring.
      High-speed transmission and analysis of large recorded ECG signals are essential,
      especially with the increased use of battery-powered devices. Exploring low-power
      alternative compression methodologies that have high efficiency and that enable
      ECG signal collection, transmission, and analysis in a smart home or remote
      location is required. Compression algorithms based on adaptive linear predictors
      and decimation by a factor B / K are evaluated based on compression ratio (CR),
      percentage root-mean-square difference (PRD), and heartbeat detection accuracy of
      the reconstructed ECG signal. With two databases (153 subjects), the new
      algorithm demonstrates the highest compression performance ( CR = 6 and PRD =
      1.88 ) and overall detection accuracy (99.90% sensitivity, 99.56% positive
      predictivity) over both databases. The proposed algorithm presents an advantage
      for the real-time transmission of ECG signals using a faster and more efficient
      method, which meets the growing demand for more efficient remote health
      monitoring.

PMID- 29337889
TI  - Reactive Oxygen Species and Mitochondrial Dynamics: The Yin and Yang of
      Mitochondrial Dysfunction and Cancer Progression.
AB  - Mitochondria are organelles with a highly dynamic ultrastructure maintained by a
      delicate equilibrium between its fission and fusion rates. Understanding the
      factors influencing this balance is important as perturbations to mitochondrial
      dynamics can result in pathological states. As a terminal site of nutrient
      oxidation for the cell, mitochondrial powerhouses harness energy in the form of
      ATP in a process driven by the electron transport chain. Contemporaneously,
      electrons translocated within the electron transport chain undergo spontaneous
      side reactions with oxygen, giving rise to superoxide and a variety of other
      downstream reactive oxygen species (ROS). Mitochondrially-derived ROS can mediate
      redox signaling or, in excess, cause cell injury and even cell death. Recent
      evidence suggests that mitochondrial ultrastructure is tightly coupled to ROS
      generation depending on the physiological status of the cell. Yet, the mechanism
      by which changes in mitochondrial shape modulate mitochondrial function and redox
      homeostasis is less clear. Aberrant mitochondrial morphology may lead to enhanced
      ROS formation, which, in turn, may deteriorate mitochondrial health and further
      exacerbate oxidative stress in a self-perpetuating vicious cycle. Here, we review
      the latest findings on the intricate relationship between mitochondrial dynamics
      and ROS production, focusing mainly on its role in malignant disease.

PMID- 29337893
TI  - Soybean-Derived Phytoalexins Improve Cognitive Function through Activation of
      Nrf2/HO-1 Signaling Pathway.
AB  - As soy-derived glyceollins are known to induce antioxidant enzymes in various
      types of cells and tissues, we hypothesized that the compounds could protect
      neurons from damage due to reactive oxygen species (ROS). In order to examine the
      neuroprotective effect of glyceollins, primary cortical neurons collected from
      mice and mouse hippocampal HT22 cells were challenged with glutamate. Glyceollins
      attenuated glutamate-induced cytotoxicity in primary cortical neuron isolated
      from mice carrying wild-type nuclear factor (erythroid-derived 2)-like 2 (Nrf2),
      but the compounds were ineffective in those isolated from Nrf2 knockout mice,
      suggesting the involvement of the Nrf2 signaling pathway in glyceollin-mediated
      neuroprotection. Furthermore, the inhibition of heme oxygenase-1 (HO-1), a major
      downstream enzyme of Nrf2, abolished the suppressive effect of glyceollins
      against glutamate-induced ROS production and cytotoxicity, confirming that
      activation of HO-1 by glyceollins is responsible for the neuroprotection. To
      examine whether glyceollins also improve cognitive ability, mice pretreated with
      glyceollins were challenged with scopolamine and subjected to behavioral tests.
      Glyceollins attenuated scopolamine-induced cognitive impairment of mice, but
      failed to enhance memory in Nrf2 knockout mice, suggesting that the memory
      enhancing effect is also mediated by the Nrf2 signaling pathway. Overall,
      glyceollins showed neuroprotection against glutamate-induced damage, and
      attenuated scopolamine-induced memory deficits in an Nrf2-dependent manner.

PMID- 29337894
TI  - Inclinometer Assembly Error Calibration and Horizontal Image Correction in
      Photoelectric Measurement Systems.
AB  - Inclinometer assembly error is one of the key factors affecting the measurement
      accuracy of photoelectric measurement systems. In order to solve the problem of
      the lack of complete attitude information in the measurement system, this paper
      proposes a new inclinometer assembly error calibration and horizontal image
      correction method utilizing plumb lines in the scenario. Based on the principle
      that the plumb line in the scenario should be a vertical line on the image plane
      when the camera is placed horizontally in the photoelectric system, the direction
      cosine matrix between the geodetic coordinate system and the inclinometer
      coordinate system is calculated firstly by three-dimensional coordinate
      transformation. Then, the homography matrix required for horizontal image
      correction is obtained, along with the constraint equation satisfying the
      inclinometer-camera system requirements. Finally, the assembly error of the
      inclinometer is calibrated by the optimization function. Experimental results
      show that the inclinometer assembly error can be calibrated only by using the
      inclination angle information in conjunction with plumb lines in the scenario.
      Perturbation simulation and practical experiments using MATLAB indicate the
      feasibility of the proposed method. The inclined image can be horizontally
      corrected by the homography matrix obtained during the calculation of the
      inclinometer assembly error, as well.

PMID- 29337895
TI  - A Coarse-Alignment Method Based on the Optimal-REQUEST Algorithm.
AB  - In this paper, we proposed a coarse-alignment method for strapdown inertial
      navigation systems based on attitude determination. The observation vectors,
      which can be obtained by inertial sensors, usually contain various types of
      noise, which affects the convergence rate and the accuracy of the coarse
      alignment. Given this drawback, we studied an attitude-determination method named
      optimal-REQUEST, which is an optimal method for attitude determination that is
      based on observation vectors. Compared to the traditional attitude-determination
      method, the filtering gain of the proposed method is tuned autonomously; thus,
      the convergence rate of the attitude determination is faster than in the
      traditional method. Within the proposed method, we developed an iterative method
      for determining the attitude quaternion. We carried out simulation and turntable
      tests, which we used to validate the proposed method's performance. The
      experiment's results showed that the convergence rate of the proposed optimal
      REQUEST algorithm is faster and that the coarse alignment's stability is higher.
      In summary, the proposed method has a high applicability to practical systems.

PMID- 29337897
TI  - Long-Term Mechanical Behavior of Nano Silica Sol Grouting.
AB  - The longevity of grouting has a significant effect on the safe and sustainable
      operation of many engineering projects. A 500-day experiment was carried out to
      study the long-term mechanical behavior of nano silica sol grouting. The nano
      silica sol was activated with different proportions of a NaCl catalyst and cured
      under fluctuating temperature and humidity conditions. The mechanical parameters
      of the grout samples were tested using an electrohydraulic uniaxial compression
      tester and an improved Vicat instrument. Scanning electron microscope, X-ray
      diffraction, and ultrasonic velocity tests were carried out to analyze the
      strength change micro-mechanism. Tests showed that as the catalyst dosage in the
      grout mix is decreased, the curves on the graphs showing changes in the weight
      and geometric parameters of the samples over time could be divided into three
      stages, a shrinkage stage, a stable stage, and a second shrinkage stage. The
      catalyst improved the stability of the samples and reduced moisture loss.
      Temperature rise was also a driving force for moisture loss. Uniaxial compressive
      stress-strain curves for all of the samples were elastoplastic. The curves for
      uniaxial compression strength and secant modulus plotted against time could be
      divided into three stages. Sample brittleness increased with time and the
      brittleness index increased with higher catalyst dosages in the latter part of
      the curing time. Plastic strength-time curves exhibit allometric scaling. Curing
      conditions mainly affect the compactness, and then affect the strength.

PMID- 29337896
TI  - Caffeic Acid and Metformin Inhibit Invasive Phenotype Induced by TGF-beta1 in C
      4I and HTB-35/SiHa Human Cervical Squamous Carcinoma Cells by Acting on Different
      Molecular Targets.
AB  - During the progression of epithelial cancer, the cells may lose epithelial
      markers and gain mesenchymal phenotype via Epithelial-Mesenchymal Transition
      (EMT). Such transformation of epithelial cancer cells to mesenchymal-like
      characteristic benefits plasticity and supports their ability to migrate. The aim
      of this study was to evaluate the influence of natural compound Caffeic Acid (CA)
      alone and in combination with antidiabetic drug Metformin (Met) on metastatic
      progression of two human cervical squamous cell cancer lines, C-4I and HTB
      35/SiHa cells. EMT program was triggered by exposition of both epithelial cell
      lines to TGF-beta1. Gene expression patterns related to epithelial/mesenchymal
      phenotype were evaluated by Real-Time PCR analysis and the protein amount was
      detected by western blot. The treatment of human squamous cancer cells with CA
      and with Met, suppressed the motility of cells and the effect depended on a
      particular cell line. Both compounds regulated the EMT process in C4-I and HTB-35
      cells by interfering with different molecular targets. In TGF-beta1-stimulated C4
      I cells, CA suppressed the expression of mesenchymal transcription factor SNAI1
      which resulted in enhanced expression of epithelial markers E-cadherin, Occludin
      and Claudin. Additionally, CA blocked MMP-9 and upregulated TIMP-1 expression, a
      specific inhibitor of MMP-9. In HTB-35 cells stimulated with TGF-beta1, Met
      decreased the expression of Vimentin. By suppressing hypoxia master regulator HIF
      1alpha, Met caused downregulation of CAIX, an enzyme involved in metastasis of
      aggressive malignant cells. In this study we showed that CA and Met inhibited EMT
      process in cancer cells via different mechanisms. However, when applied together,
      compounds exerted the greater effect on EMT than each compound alone. This is the
      first report revealing that CA alone and co-treated with Met may reverse
      mesenchymal phenotype of TGF-beta1-treated cervical tumor cells and we believe
      that the use of the two small molecules may be considered as a potential
      therapeutic approach for metastatic cervical cancer.

PMID- 29337899
TI  - Synergistic Effects of Copper Sites on Apparent Stability of Multicopper Oxidase,
      Fet3p.
AB  - Saccharomyces cerevisiae Fet3p is a multicopper oxidase that contains three
      cupredoxin-like domains and four copper ions located in three distinct metal
      sites (T1 in domain 3; T2 and the binuclear T3 at the interface between domains 1
      and 3). To probe the role of the copper sites in Fet3p thermodynamic stability,
      we performed urea-induced unfolding experiments with holo-, apo- and three
      partially-metallated (T1, T2 and T1/T2 sites depleted of copper) forms of Fet3p.
      Using a combination of spectroscopic probes (circular dichroism, fluorescence
      intensity and maximum, 8-anilinonaphthalene-1-sulfonic acid (ANS) emission,
      oxidase activity and blue color), we reveal that all forms of Fet3p unfold in a
      four-state reaction with two partially-folded intermediates. Using phase
      diagrams, it emerged that Fet3p with all copper sites filled had a significantly
      higher stability as compared to the combined contributions of the individual
      copper sites. Hence, there is long-range inter-domain communication between
      distal copper sites that contribute to overall Fet3p stability.

PMID- 29337900
TI  - Age-Related Epigenetic Derangement upon Reprogramming and Differentiation of
      Cells from the Elderly.
AB  - Aging is a complex multi-layered phenomenon. The study of aging in humans is
      based on the use of biological material from hard-to-gather tissues and highly
      specific cohorts. The introduction of cell reprogramming techniques posed
      promising features for medical practice and basic research. Recently, a growing
      number of studies have been describing the generation of induced pluripotent stem
      cells (iPSCs) from old or centenarian biologic material. Nonetheless,
      Reprogramming techniques determine a profound remodelling on cell epigenetic
      architecture whose extent is still largely debated. Given that cell epigenetic
      profile changes with age, the study of cell-fate manipulation approaches on cells
      deriving from old donors or centenarians may provide new insights not only on
      regenerative features and physiology of these cells, but also on reprogramming
      associated and age-related epigenetic derangement.

PMID- 29337902
TI  - Cytokine Disturbances in Coronary Artery Ectasia Do Not Support Atherosclerosis
      Pathogenesis.
AB  - BACKGROUND: Coronary artery ectasia (CAE) is a rare disorder commonly associated
      with additional features of atherosclerosis. In the present study, we aimed to
      examine the systemic immune-inflammatory response that might associate CAE.
      METHODS: Plasma samples were obtained from 16 patients with coronary artery
      ectasia (mean age 64.9 +/- 7.3 years, 6 female), 69 patients with coronary artery
      disease (CAD) and angiographic evidence for atherosclerosis (age 64.5 +/- 8.7
      years, 41 female), and 140 controls (mean age 58.6 +/- 4.1 years, 40 female) with
      normal coronary arteries. Samples were analyzed at Umea University Biochemistry
      Laboratory, Sweden, using the V-PLEX Pro-Inflammatory Panel 1 (human) Kit.
      Statistically significant differences (p < 0.05) between patient groups and
      controls were determined using Mann-Whitney U-tests. RESULTS: The CAE patients
      had significantly higher plasma levels of INF-gamma, TNF-alpha, IL-1beta, and IL
      8 (p = 0.007, 0.01, 0.001, and 0.002, respectively), and lower levels of IL-2 and
      IL-4 (p < 0.001 for both) compared to CAD patients and controls. The plasma
      levels of IL-10, IL-12p, and IL-13 were not different between the three groups.
      None of these markers could differentiate between patients with pure (n = 6) and
      mixed with minimal atherosclerosis (n = 10) CAE. CONCLUSIONS: These results
      indicate an enhanced systemic pro-inflammatory response in CAE. The profile of
      this response indicates activation of macrophages through a pathway and trigger
      different from those of atherosclerosis immune inflammatory response.

PMID- 29337901
TI  - Transcriptional-Readthrough RNAs Reflect the Phenomenon of "A Gene Contains
      Gene(s)" or "Gene(s) within a Gene" in the Human Genome, and Thus Are Not
      Chimeric RNAs.
AB  - Tens of thousands of chimeric RNAs, i.e., RNAs with sequences of two genes, have
      been identified in human cells. Most of them are formed by two neighboring genes
      on the same chromosome and are considered to be derived via transcriptional
      readthrough, but a true readthrough event still awaits more evidence and trans
      splicing that joins two transcripts together remains as a possible mechanism. We
      regard those genomic loci that are transcriptionally read through as unannotated
      genes, because their transcriptional and posttranscriptional regulations are the
      same as those of already-annotated genes, including fusion genes formed due to
      genetic alterations. Therefore, readthrough RNAs and fusion-gene-derived RNAs are
      not chimeras. Only those two-gene RNAs formed at the RNA level, likely via trans
      splicing, without corresponding genes as genomic parents, should be regarded as
      authentic chimeric RNAs. However, since in human cells, procedural and
      mechanistic details of trans-splicing have never been disclosed, we doubt the
      existence of trans-splicing. Therefore, there are probably no authentic chimeras
      in humans, after readthrough and fusion-gene derived RNAs are all put back into
      the group of ordinary RNAs. Therefore, it should be further determined whether in
      human cells all two-neighboring-gene RNAs are derived from transcriptional
      readthrough and whether trans-splicing truly exists.

PMID- 29337903
TI  - Use of Accelerometer Activity Monitors to Detect Changes in Pruritic Behaviors:
      Interim Clinical Data on 6 Dogs.
AB  - Veterinarians and pet owners have limited ability to assess pruritic behaviors in
      dogs. This pilot study assessed the capacity of the Vetrax(r) triaxial
      accelerometer to measure these behaviors in six dogs with pruritus likely due to
      environmental allergens. Dogs wore the activity monitor for two weeks while
      consuming their usual pet food (baseline), then for eight weeks while consuming a
      veterinary-exclusive pet food for dogs with suspected non-food-related skin
      conditions (Hill's Prescription Diet(r) Derm DefenseTM Canine dry food).
      Veterinarians and owners completed questionnaires during baseline, phase 1 (days
      1-28) and phase 2 (days 29-56) without knowledge of the activity data. Continuous
      3-axis accelerometer data was processed using proprietary behavior recognition
      algorithms and analyzed using general linear mixed models with false discovery
      rate-adjusted p values. Veterinarian-assessed overall clinical signs of pruritus
      were significantly predicted by scratching (beta 0.176, p = 0.008), head shaking
      (beta 0.197, p < 0.001) and sleep quality (beta -0.154, p < 0.001), while owner
      assessed quality of life was significantly predicted by scratching (beta -0.103,
      p = 0.013) and head shaking (beta -0.146, p < 0.001). Among dogs exhibiting
      pruritus signs eating the veterinary-exclusive food, the Vetrax(r) sensor
      provided an objective assessment of clinically relevant pruritic behaviors that
      agreed with owner and veterinarian reports.

PMID- 29337904
TI  - Maternal Exposure to PM2.5 during Pregnancy Induces Impaired Development of
      Cerebral Cortex in Mice Offspring.
AB  - Air pollution is a serious environmental health problem closely related to the
      occurrence of central nervous system diseases. Exposure to particulate matter
      with an aerodynamic diameter less than or equal to 2.5 um (PM2.5) during
      pregnancy may affect the growth and development of infants. The present study was
      to investigate the effects of maternal exposure to PM2.5 during pregnancy on
      brain development in mice offspring. Pregnant mice were randomly divided into
      experimental groups of low-, medium-, or high-dosages of PM2.5, a mock-treated
      group which was treated with the same amount of phosphate buffer solution (PBS),
      and acontrol group which was untreated. The ethology of offspring mice on
      postnatal days 1, 7, 14, 21, and 30, along with neuronal development and
      apoptosis in the cerebral cortex were investigated. Compared with the control,
      neuronal mitochondrial cristae fracture, changed autophagy characteristics,
      significantly increased terminal deoxynucleotidyl transferase dUTP nick end
      labeling (TUNEL) positive cell rate, and mRNA levels of apoptosis-related caspase
      8 and caspase-9 were found in cerebral cortex of mice offspring from the
      treatment groups, with mRNA levels of Bcl-2 and ratio of Bcl-2 to Bax decreased.
      Treatment groups also demonstrated enhanced protein expressions of apoptosis
      related cleaved caspase-3, cleaved caspase-8 and cleaved caspase-9, along with
      declined proliferating cell nuclear antigen (PCNA), Bcl-2, and ratio of Bcl-2 to
      Bax. Open field experiments and tail suspension experiments showed that exposure
      to high dosage of PM2.5 resulted in decreased spontaneous activities but
      increased static accumulation time in mice offspring, indicating anxiety,
      depression, and social behavioral changes. Our results suggested that maternal
      exposure to PM2.5 during pregnancy might interfere with cerebral cortex
      development in mice offspring by affecting cell apoptosis.

PMID- 29337905
TI  - The Role of miRNAs in the Pathophysiology of Liver Diseases and Toxicity.
AB  - Both acute and chronic liver toxicity represents a major global health burden and
      an important cause of morbidity and lethality worldwide. Despite epochal progress
      in the treatment of hepatitis C virus infections, pharmacological treatment
      strategies for most liver diseases are still limited and new targets for
      prevention or treatment of liver disease are urgently needed. MicroRNAs (miRNAs)
      represent a new class of highly conserved small non-coding RNAs that are involved
      in the regulation of gene expression by targeting whole networks of so called
      "targets". Previous studies have shown that the expression of miRNAs is
      specifically altered in almost all acute and chronic liver diseases. In this
      context, it was shown that miRNA can exert causal roles, being pro- or anti
      inflammatory, as well as pro- or antifibrotic mediators or being oncogenes as
      well as tumor suppressor genes. Recent data suggested a potential therapeutic use
      of miRNAs by targeting different steps in the hepatic pathophysiology. Here, we
      review the function of miRNAs in the context of acute and chronic liver diseases.
      Furthermore, we highlight the potential role of circulating microRNAs in
      diagnosis of liver diseases and discuss the major challenges and drawbacks that
      currently prevent the use of miRNAs in clinical routine.

PMID- 29337906
TI  - Specific Collagen Peptides Improve Bone Mineral Density and Bone Markers in
      Postmenopausal Women-A Randomized Controlled Study.
AB  - Introduction: Investigations in rodents as well as in vitro experiments have
      suggested an anabolic influence of specific collagen peptides (SCP) on bone
      formation and bone mineral density (BMD). The goal of the study was to
      investigate the effect of 12-month daily oral administration of 5 g SCP vs.
      placebo (CG: control group) on BMD in postmenopausal women with primary, age
      related reduction in BMD. Methods: 131 women were enrolled in this randomized,
      placebo-controlled double-blinded investigation. The primary endpoint was the
      change in BMD of the femoral neck and the spine after 12 months. In addition,
      plasma levels of bone markers-amino-terminal propeptide of type I collagen (P1NP)
      and C-telopeptide of type I collagen (CTX 1)-were analysed. Results: A total of
      102 women completed the study, but all subjects were included in the intention-to
      treat (ITT) analysis (age 64.3 +/- 7.2 years; Body Mass Index, BMI 23.6 +/- 3.6
      kg/m2; T-score spine -2.4 +/- 0.6; T-score femoral neck -1.4 +/- 0.5). In the SCP
      group (n = 66), BMD of the spine and of the femoral neck increased significantly
      compared to the control group (n = 65) (T-score spine: SCP +0.1 +/- 0.26; CG 
      0.03 +/- 0.18; ANCOVA p = 0.030; T-score femoral neck: SCP +0.09 +/- 0.24; CG 
      0.01 +/- 0.19; ANCOVA p = 0.003). P1NP increased significantly in the SCP group
      (p = 0.007), whereas CTX 1 increased significantly in the control group (p =
      0.011). Conclusions: These data demonstrate that the intake of SCP increased BMD
      in postmenopausal women with primary, age-related reduction of BMD. In addition,
      SCP supplementation was associated with a favorable shift in bone markers,
      indicating increased bone formation and reduced bone degradation.

PMID- 29337907
TI  - Few Sex Differences in Hospitalized Suicide Attempters Aged 70 and Above.
AB  - Relatively little research attention has been paid to sex issues in late life
      suicidal behaviour. The aim was to compare clinical characteristics of women and
      men aged 70+ who were hospitalized after a suicide attempt. We hypothesized
      higher depression and anxiety scores in women, and we expected to find that men
      would more often attribute the attempt to health problems and compromised
      autonomy. Participants (56 women and 47 men, mean age 80) were interviewed by a
      psychologist. In addition to psychiatric and somatic health assessments,
      participants responded to an open-ended question concerning attributions of the
      attempt. There were no sex differences in depression and anxiety. Forty-five
      percent of the men and 14% of the women had a history of substance use disorder
      (p = 0.02). At least one serious physical disability was noted in 60.7% of the
      women and 53.2% of the men (p = 0.55). Proportions attributing their attempt to
      somatic illness did not differ (women, 14.5% vs. men 17.4%, p = 0.79), and
      similar proportions attributed the attempt to reduced autonomy (women, 21.8% vs.
      men, 26.1%, p = 0.64). We found strikingly similar figures for depression scores,
      functional disability and attributions for attempting suicide in older men and
      women. Larger studies are needed in diverse settings as sex differences might be
      influenced by cultural context.

PMID- 29337909
TI  - Salvia Species as Sources of Natural Products with Antiprotozoal Activity.
AB  - Natural products from plants have been used since ancestral times to treat a wide
      variety of diseases worldwide. Plants of the genus Salvia (Sage) have been
      reported to be used for the prevention and treatment of various diseases and
      ailments. In particular, some Salvia species have been used in traditional
      medicine to treat diseases caused by protozoan parasites of the genera
      Trypanosoma, Leishmania and Plasmodium and scientific studies have demonstrated
      the activity of various isolated constituents from these plants against these
      pathogens. The current review attempts to give a critical overview of published
      information about the antiprotozoal activity of species of the genus Salvia and
      their chemical constituents. It is meant to give a unified overview of these
      results in order to avoid repetitions caused, e.g., by limited access to some
      primary reports, and to stimulate further research to possibly facilitate the
      development of new molecular leads against protozoal neglected tropical diseases
      (NTDs) based on Salvia constituents.

PMID- 29337911
TI  - Throughput Analysis on 3-Dimensional Underwater Acoustic Network with One-Hop
      Mobile Relay.
AB  - Underwater acoustic communication network (UACN) has been considered as an
      essential infrastructure for ocean exploitation. Performance analysis of UACN is
      important in underwater acoustic network deployment and management. In this
      paper, we analyze the network throughput of three-dimensional randomly deployed
      transmitter-receiver pairs. Due to the long delay of acoustic channels,
      complicated networking protocols with heavy signaling overhead may not be
      appropriate. In this paper, we consider only one-hop or two-hop transmission, to
      save the signaling cost. That is, we assume the transmitter sends the data packet
      to the receiver by one-hop direct transmission, or by two-hop transmission via
      mobile relays. We derive the closed-form formulation of packet delivery rate with
      respect to the transmission delay and the number of transmitter-receiver pairs.
      The correctness of the derivation results are verified by computer simulations.
      Our analysis indicates how to obtain a precise tradeoff between the delay
      constraint and the network capacity.

PMID- 29337910
TI  - Network-Based Methods for Identifying Key Active Proteins in the Extracellular
      Electron Transfer Process in Shewanella oneidensis MR-1.
AB  - Shewanella oneidensis MR-1 can transfer electrons from the intracellular
      environment to the extracellular space of the cells to reduce the extracellular
      insoluble electron acceptors (Extracellular Electron Transfer, EET). Benefiting
      from this EET capability, Shewanella has been widely used in different areas,
      such as energy production, wastewater treatment, and bioremediation. Genome-wide
      proteomics data was used to determine the active proteins involved in activating
      the EET process. We identified 1012 proteins with decreased expression and 811
      proteins with increased expression when the EET process changed from inactivation
      to activation. We then networked these proteins to construct the active protein
      networks, and identified the top 20 key active proteins by network centralization
      analysis, including metabolism- and energy-related proteins, signal and
      transcriptional regulatory proteins, translation-related proteins, and the EET
      related proteins. We also constructed the integrated protein interaction and
      transcriptional regulatory networks for the active proteins, then found three
      exclusive active network motifs involved in activating the EET process-Bi
      feedforward Loop, Regulatory Cascade with a Feedback, and Feedback with a Protein
      Protein Interaction (PPI)-and identified the active proteins involved in these
      motifs. Both enrichment analysis and comparative analysis to the whole-genome
      data implicated the multiheme c-type cytochromes and multiple signal processing
      proteins involved in the process. Furthermore, the interactions of these motif
      guided active proteins and the involved functional modules were discussed.
      Collectively, by using network-based methods, this work reported a proteome-wide
      search for the key active proteins that potentially activate the EET process.

PMID- 29337912
TI  - Social Incentive Mechanism Based Multi-User Sensing Time Optimization in Co
      Operative Spectrum Sensing with Mobile Crowd Sensing.
AB  - Co-operative spectrum sensing emerging as a significant method to improve the
      utilization of the spectrum needs sufficient sensing users to participate.
      Existing related papers consider only the limited secondary users in current
      sensing system and assume that they will always perform the co-operative spectrum
      sensing out of obligation. However, this assumption is impractical in the
      realistic situation where the secondary users are rational and they will not join
      in the co-operative sensing process without a certain reward to compensate their
      sensing energy consumption, especially the ones who have no data transmitting in
      current time slot. To solve this problem, we take advantage of the mobile crowd
      sensing to supply adequate co-operative sensing candidates, in which the sensing
      users are not only the secondary users but also a crowd of widely distributed
      mobile users equipped with personal spectrum sensors (such as smartphones,
      vehicle sensors). Furthermore, a social incentive mechanism is also adapted to
      motivate the participations of mobile sensing users. In this paper, we model the
      interactions among the motivated sensing users as a co-operative game where they
      adjust their own sensing time strategies to maximize the co-operative sensing
      utility, which eventually guarantees the detection performance and prevents the
      global sensing cost being too high. We prove that the game based optimization
      problem is NP-hard and exists a unique optimal equilibrium. An improved
      differential evolution algorithm is proposed to solve the optimization problem.
      Simulation results prove the better performance in our proposed multi-user
      sensing time optimization model and the proposed improved differential evolution
      algorithm, respectively compared with the non-optimization model and the other
      two typical equilibrium solution algorithms.

PMID- 29337913
TI  - Proteomic Analysis and Identification of Possible Allergenic Proteins in Mature
      Pollen of Populus tomentosa.
AB  - Pollen grains from Populus tomentosa, a widely cultivated tree in northern area
      of China, are considered to be an important aeroallergen causing severe allergic
      diseases. To gain insight into their allergenic components, mature Populus
      tomentosa pollen proteins were analyzed by two-dimensional gel electrophoresis (2
      DE) and matrix-assisted laser desorption/ionization-time of flight mass
      spectrometry (MALDI-TOF/TOF MS). A total of 412 spots from mature pollen were
      resolved on pH 4-7 immobilized pH gradient (IPG) strips and 159 distinct proteins
      were identified from 242 spots analyzed. The identified proteins were categorized
      based on their functional role in the pollen, which included proteins involved in
      energy regulation, protein fate, protein synthesis and processing, metabolism,
      defense/stress responses, development and other functional categories. Moreover,
      among the identified proteins, 27 proteins were identified as putative allergens
      using the Structural Database of Allergenic Proteins (SDAP) tool and Allergen
      Online. The expression patterns of these putative allergen genes indicate that
      several of these genes are highly expressed in pollen. The identified putative
      allergens have the potential to improve specific diagnosis and can be used to
      develop vaccines for immunotherapy against poplar pollen allergy.

PMID- 29337914
TI  - Acoustic Transducers as Passive Cooperative Targets for Wireless Sensing of the
      Sub-Surface World: Challenges of Probing with Ground Penetrating RADAR.
AB  - Passive wireless transducers are used as sensors, probed by a RADAR system. A
      simple way to separate the returning signal from the clutter is to delay the
      response, so that the clutter decays before the echoes are received. This can be
      achieved by introducing a fixed delay in the sensor design. Acoustic wave
      transducers are ideally suited as cooperative targets for passive, wireless
      sensing. The incoming electromagnetic pulse is converted into an acoustic wave,
      propagated on the sensor substrate surface, and reflected as an electromagnetic
      echo. According to a known law, the acoustic wave propagation velocity depends on
      the physical quantity under investigation, which is then measured as an echo
      delay. Both conversions between electromagnetic and acoustic waves are based on
      the piezoelectric property of the substrate of which the sensor is made.
      Investigating underground sensing, we address the problems of using GPR (Ground
      Penetrating RADAR) for probing cooperative targets. The GPR is a good candidate
      for this application because it provides an electromagnetic source and receiver,
      as well as echo recording tools. Instead of designing dedicated electronics, we
      choose a commercially available, reliable and rugged instrument. The measurement
      range depends on parameters like antenna radiation pattern, radio spectrum
      matching between GPR and the target, antenna-sensor impedance matching and the
      transfer function of the target. We demonstrate measurements at depths ranging
      from centimeters to circa 1 m in a sandbox. In our application, clutter rejection
      requires delays between the emitted pulse and echoes to be longer than in the
      regular use of the GPR for geophysical measurements. This delay, and the accuracy
      needed for sensing, challenge the GPR internal time base. In the GPR units we
      used, the drift turns out to be incompatible with the targeted application. The
      available documentation of other models and brands suggests that this is a rather
      general limitation. We solved the problem by replacing the analog ramp generator
      defining the time base with a fully digital solution, whose time accuracy and
      stability relies on a quartz oscillator. The resulting stability is acceptable
      for sub-surface cooperative sensor measurement.

PMID- 29337915
TI  - Comparing Classic and Interval Analytical Hierarchy Process Methodologies for
      Measuring Area-Level Deprivation to Analyze Health Inequalities.
AB  - Deprivation indices are useful measures to study health inequalities. Different
      techniques are commonly applied to construct deprivation indices, including multi
      criteria decision methods such as the analytical hierarchy process (AHP). The
      multi-criteria deprivation index for the city of Quito is an index in which
      indicators are weighted by applying the AHP. In this research, a variation of
      this index is introduced that is calculated using interval AHP methodology. Both
      indices are compared by applying logistic generalized linear models and
      multilevel models, considering self-reported health as the dependent variable and
      deprivation and self-reported quality of life as the independent variables. The
      obtained results show that the multi-criteria deprivation index for the city of
      Quito is a meaningful measure to assess neighborhood effects on self-reported
      health and that the alternative deprivation index using the interval AHP
      methodology more thoroughly represents the local knowledge of experts and
      stakeholders. These differences could support decision makers in improving health
      planning and in tackling health inequalities in more deprived areas.

PMID- 29337916
TI  - Real Time Cascade Impactor Based On Surface Acoustic Wave Delay Lines for PM10
      and PM2.5 Mass Concentration Measurement.
AB  - In this research, Surface Acoustic Wave (SAW) sensors are combined with a cascade
      impactor to perform real time PM10 and PM2.5 mass concentration measurements. The
      SAW sensors consist of 125 MHz delay lines based on Love waves propagating on an
      AT-cut quartz substrate. The Love waves are guided on the substrate's surface
      using a silica layer. SAW sensors themselves are not capable to discriminate
      particles by their size, therefore, particle separation based on aerodynamic
      diameter is achieved using a 3 Lpm dedicated cascade impactor. The latter was
      designed to integrate the SAW sensors which are monitored using a phase shift
      measurement. The collected particles impact on the acoustic sensor's surface
      inducing a gravimetric effect that modifies the acoustic wave propagation
      conditions. The resulted phase shift allows the measurement of the mass deposited
      on the sensitive zone. The novel cascade impactor with SAW sensors as particle
      collecting stages is exposed to different aerosols in the 0-150 MUg/m3
      concentration range and proved to be able to detect and differentiate particles
      based on their size in real time. The system's response was compared to a
      commercial optical counter based on light scattering technology and was found to
      be in good agreement with it.

PMID- 29337917
TI  - The HydroColor App: Above Water Measurements of Remote Sensing Reflectance and
      Turbidity Using a Smartphone Camera.
AB  - HydroColor is a mobile application that utilizes a smartphone's camera and
      auxiliary sensors to measure the remote sensing reflectance of natural water
      bodies. HydroColor uses the smartphone's digital camera as a three-band
      radiometer. Users are directed by the application to collect a series of three
      images. These images are used to calculate the remote sensing reflectance in the
      red, green, and blue broad wavelength bands. As with satellite measurements, the
      reflectance can be inverted to estimate the concentration of absorbing and
      scattering substances in the water, which are predominately composed of suspended
      sediment, chlorophyll, and dissolved organic matter. This publication describes
      the measurement method and investigates the precision of HydroColor's reflectance
      and turbidity estimates compared to commercial instruments. It is shown that
      HydroColor can measure the remote sensing reflectance to within 26% of a
      precision radiometer and turbidity within 24% of a portable turbidimeter.
      HydroColor distinguishes itself from other water quality camera methods in that
      its operation is based on radiometric measurements instead of image color.
      HydroColor is one of the few mobile applications to use a smartphone as a
      completely objective sensor, as opposed to subjective user observations or color
      matching using the human eye. This makes HydroColor a powerful tool for
      crowdsourcing of aquatic optical data.

PMID- 29337918
TI  - Polyacrylamide Ferrogels with Magnetite or Strontium Hexaferrite: Next Step in
      the Development of Soft Biomimetic Matter for Biosensor Applications.
AB  - Magnetic biosensors are an important part of biomedical applications of magnetic
      materials. As the living tissue is basically a "soft matter." this study
      addresses the development of ferrogels (FG) with micron sized magnetic particles
      of magnetite and strontium hexaferrite mimicking the living tissue. The basic
      composition of the FG comprised the polymeric network of polyacrylamide,
      synthesized by free radical polymerization of monomeric acrylamide (AAm) in water
      solution at three levels of concentration (1.1 M, 0.85 M and 0.58 M) to provide
      the FG with varying elasticity. To improve FG biocompatibility and to prevent the
      precipitation of the particles, polysaccharide thickeners-guar gum or xanthan gum
      were used. The content of magnetic particles in FG varied up to 5.2 wt %
      depending on the FG composition. The mechanical properties of FG and their
      deformation in a uniform magnetic field were comparatively analyzed. FG filled
      with strontium hexaferrite particles have larger Young's modulus value than FG
      filled with magnetite particles, most likely due to the specific features of the
      adhesion of the network's polymeric subchains on the surface of the particles. FG
      networks with xanthan are stronger and have higher modulus than the FG with guar.
      FG based on magnetite, contract in a magnetic field 0.42 T, whereas some FG based
      on strontium hexaferrite swell. Weak FG with the lowest concentration of AAm
      shows a much stronger response to a field, as the concentration of AAm governs
      the Young's modulus of ferrogel. A small magnetic field magnetoimpedance sensor
      prototype with Co68.6Fe3.9Mo3.0Si12.0B12.5 rapidly quenched amorphous ribbon
      based element was designed aiming to develop a sensor working with a disposable
      stripe sensitive element. The proposed protocol allowed measurements of the
      concentration dependence of magnetic particles in gels using magnetoimpedance
      responses in the presence of magnetite and strontium hexaferrite ferrogels with
      xanthan. We have discussed the importance of magnetic history for the detection
      process and demonstrated the importance of remnant magnetization in the case of
      the gels with large magnetic particles.

PMID- 29337919
TI  - Functional Impact of the N-terminal Arm of Proline Dehydrogenase from Thermus
      thermophilus.
AB  - Proline dehydrogenase (ProDH) is a ubiquitous flavoenzyme that catalyzes the
      oxidation of proline to Delta1-pyrroline-5-carboxylate. Thermus thermophilus
      ProDH (TtProDH) contains in addition to its flavin-binding domain an N-terminal
      arm, consisting of helices alphaA, alphaB, and alphaC. Here, we report the
      biochemical properties of the helical arm truncated TtProDH variants DeltaA,
      DeltaAB, and DeltaABC, produced with maltose-binding protein as solubility tag.
      All three truncated variants show similar spectral properties as TtProDH,
      indicative of a conserved flavin-binding pocket. DeltaA and DeltaAB are highly
      active tetramers that rapidly react with the suicide inhibitor N
      propargylglycine. Removal of the entire N-terminal arm (DeltaABC) results in
      barely active dimers that are incapable of forming a flavin adduct with N
      propargylglycine. Characterization of V32D, Y35F, and V36D variants of DeltaAB
      established that a hydrophobic patch between helix alphaC and helix alpha8 is
      critical for TtProDH catalysis and tetramer stabilization.

PMID- 29337920
TI  - Acute Traumatic Endotheliopathy in Isolated Severe Brain Injury and Its Impact on
      Clinical Outcome.
AB  - STUDY DESIGN: Prospective observational cohort. OBJECTIVE: To investigate the
      difference in plasma levels of syndecan-1 (due to glycocalyx degradation) and
      soluble thrombomodulin (due to endothelial damage) in isolated severe traumatic
      brain injury (TBI) patients with/without early coagulopathy. A secondary
      objective was to compare the effects of the degree of TBI endotheliopathy on
      hospital mortality among patients with TBI-associated coagulopathy (TBI-AC).
      METHODS: Data was prospectively collected on isolated severe TBI (sTBI) patients
      with Glasgow Coma Scale (GCS) <=8 less than 12 h after injury admitted to a level
      I trauma centre. Isolated sTBI patients with samples withdrawn prior to blood
      transfusion were stratified by conventional coagulation tests as coagulopathic
      (prothrombin time (PT) >= 16.7 s, international normalized ratio (INR) >= 1.27,
      and activated partial thromboplastin time (aPTT) >= 28.8 s) and non
      coagulopathic. Twenty healthy controls were also included. Plasma levels of
      thrombomodulin and syndecan-1 were estimated by ELISA. With receiver operating
      characteristic curve (ROC) analysis, we defined endotheliopathy as a syndecan-1
      cut-off level that maximized the sum of sensitivity and specificity for
      predicting TBI-AC. RESULTS: Inclusion criteria were met in 120 cases, with
      subjects aged 35.5 +/- 12.6 years (88.3% males). TBI-AC was identified in 50
      (41.6%) patients, independent of age, gender, and GCS, but there was an
      association with acidosis (60%; p = 0.01). Following isolated sTBI, we found
      insignificant changes in soluble thrombomodulin (sTM) levels between patients
      with isolated TBI and controls, and sTM levels were lower in coagulopathic
      compared to non-coagulopathic patients. Elevations in plasma syndecan-1 (ng/mL)
      levels were seen compared to control (31.1(21.5-30.6) vs. 24.8(18.5-30.6); p =
      0.08). Syndecan-1(ng/mL) levels were significantly elevated in coagulopathic
      compared to non-coagulopathic patients (33.7(21.6-109.5) vs. 29.9(19.239.5); p =
      0.03). Using ROC analysis (area under the curve = 0.61; 95% Confidence Interval
      (CI) 0.50 to 0.72), we established a plasma syndecan-1 level cutoff of >=30.5
      ng/mL (sensitivity % = 55.3, specificity % = 52.3), with a significant
      association with TBI-associated coagulopathy. CONCLUSION: Subsequent to brain
      injury, elevated syndecan-1 shedding and endotheliopathy may be associated with
      early coagulation abnormalities. A syndecan-1 level >=30.5 ng/mL identified
      patients with TBI-AC, and may be of importance in guiding management and clinical
      decision-making.

PMID- 29337921
TI  - Unified Compact ECC-AES Co-Processor with Group-Key Support for IoT Devices in
      Wireless Sensor Networks.
AB  - Security is a critical challenge for the effective expansion of all new emerging
      applications in the Internet of Things paradigm. Therefore, it is necessary to
      define and implement different mechanisms for guaranteeing security and privacy
      of data interchanged within the multiple wireless sensor networks being part of
      the Internet of Things. However, in this context, low power and low area are
      required, limiting the resources available for security and thus hindering the
      implementation of adequate security protocols. Group keys can save resources and
      communications bandwidth, but should be combined with public key cryptography to
      be really secure. In this paper, a compact and unified co-processor for enabling
      Elliptic Curve Cryptography along to Advanced Encryption Standard with low area
      requirements and Group-Key support is presented. The designed co-processor allows
      securing wireless sensor networks with independence of the communications
      protocols used. With an area occupancy of only 2101 LUTs over Spartan 6 devices
      from Xilinx, it requires 15% less area while achieving near 490% better
      performance when compared to cryptoprocessors with similar features in the
      literature.

PMID- 29337922
TI  - Underdetermined Wideband DOA Estimation for Off-Grid Sources with Coprime Array
      Using Sparse Bayesian Learning.
AB  - Sparse Bayesian learning (SBL) is applied to the coprime array for
      underdetermined wideband direction of arrival (DOA) estimation. Using the
      augmented covariance matrix, the coprime array can achieve a higher number of
      degrees of freedom (DOFs) to resolve more sources than the number of physical
      sensors. The sparse-based DOA estimation can deteriorate the detection and
      estimation performance because the sources may be off the search grid no matter
      how fine the grid is. This dictionary mismatch problem can be well resolved by
      the SBL using fixed point updates. The SBL can automatically choose sparsity and
      approximately resolve the non-convex optimizaton problem. Numerical simulations
      are conducted to validate the effectiveness of the underdetermined wideband DOA
      estimation via SBL based on coprime array. It is clear that SBL can obtain good
      performance in detection and estimation compared to least absolute shrinkage and
      selection operator (LASSO), simultaneous orthogonal matching pursuit least
      squares (SOMP-LS) , simultaneous orthogonal matching pursuit total least squares
      (SOMP-TLS) and off-grid sparse Bayesian inference (OGSBI).

PMID- 29337923
TI  - Synergistic Antifungal, Allelopatic and Anti-Proliferative Potential of Salvia
      officinalis L., and Thymus vulgaris L. Essential Oils.
AB  - The current study aimed to investigate the chemical composition and the
      synergistic potential of two essential oils (EOs), as obtained from Salvia
      officinalis L. (SEO), and Thymus vulgaris L. (TEO). The antifungal potential was
      tested in vitro against Fusarium graminearum (Fg 06_17), the herbicidal effect
      was studied using weed seeds of Amaranthus retroflexus (ARET), Chenopodium album
      (CALB), Echinochloa crus-galli (EGAL), but also wheat seeds (WS) of the Lovrin
      variety and tomato seeds Saint-Pierre of the variety. The GC-MS profile
      highlights that the mains compounds identified in SEO were: caryophyllene
      (25.364%), camphene (14.139%), eucalyptol (13.902%), and beta-pinene (11.230%),
      while in TEO, the predominant phytochemicals were: gamma-terpinene (68.415%) and
      p-thymol (24.721%). The results indicated that the tested EOs alone as well as in
      combination have allelopathic effect against investigated seeds, while the
      synergistic effect of TEO and SEO in terms of fungal growth was demonstrated at a
      level of 0.06%. Thyme and sage EOs exhibited in vitro anti-proliferative activity
      on two melanoma cell lines, namely A375 human melanoma and B164A5 mouse melanoma
      alone, as well as in combination. SEO was most effective in terms of decreasing
      the cell viability of murine and human melanoma cell lines when compared to TEO.

PMID- 29337924
TI  - Effect of Humid Aging on the Oxygen Adsorption in SnO2 Gas Sensors.
AB  - To investigate the effect of aging at 580  degrees C in wet air (humid aging) on
      the oxygen adsorption on the surface of SnO2 particles, the electric properties
      and the sensor response to hydrogen in dry and humid atmospheres for SnO2
      resistive-type gas sensors were evaluated. The electric resistance in dry and wet
      atmospheres at 350  degrees C was strongly increased by humid aging. From the
      results of oxygen partial pressure dependence of the electric resistance, the
      oxygen adsorption equilibrium constants (K1; for O- adsorption, K2; for O2-
      adsorption) were estimated on the basis of the theoretical model of oxygen
      adsorption. The K1 and K2 in dry and wet atmospheres at 350  degrees C were
      increased by humid aging at 580  degrees C, indicating an increase in the
      adsorption amount of both O- and O2-. These results suggest that hydroxyl
      poisoning on the oxygen adsorption is suppressed by humid aging. The sensor
      response to hydrogen in dry and wet atmosphere at 350  degrees C was clearly
      improved by humid aging. Such an improvement of the sensor response seems to be
      caused by increasing the oxygen adsorption amount. Thus, the humid aging offers
      an effective way to improve the sensor response of SnO2 resistive-type gas
      sensors in dry and wet atmospheres.

PMID- 29337927
TI  - The Plant Growth-Promoting Fungus (PGPF) Alternaria sp. A13 Markedly Enhances
      Salvia miltiorrhiza Root Growth and Active Ingredient Accumulation under
      Greenhouse and Field Conditions.
AB  - Plant growth-promoting fungi (PGPF) have attracted considerable interest as bio
      fertilisers due to their multiple beneficial effects on plant quantity and
      quality and their positive relationship with the ecological environment.
      Advancements in the development of PGPF for crops and economic plant cultivation
      applications have been achieved, but such improvements for the use of PGPF with
      popular medicinal herbs, such as Salvia miltiorrhiza, are rare. In this study, we
      collected S. miltiorrhiza specimens inhabiting wild, semi-wild, farmland and pot
      cultured areas in the Henan province of China and isolated endophytes from the
      roots, shoots and leaves of these samples. Twenty-eight strains of the dominant
      genus Alternaria were identified and selected as candidate PGPF. Under greenhouse
      conditions, Alternaria sp. A13 simultaneously enhanced the dry root biomass and
      secondary metabolite accumulation of S. miltiorrhiza as the optimal PGPF of the
      28 candidate isolates. To further assess the interaction between S. miltiorrhiza
      and Alternaria sp. A13, the effects on seedlings growth, active ingredient
      accumulation, and the activity of key enzymes for effective biosynthetic pathways
      were investigated over a period of six months under field conditions. Compared to
      uninoculated seedlings, S. miltiorrhiza seedlings colonised by Alternaria sp. A13
      showed significant increment of 140% in fresh weight, 138% in dry weight, and
      enhancement in the contents of total phenolic acid, lithospermic acids A and B
      (LAA and LAB, respectively) of 210%, 128% and 213%, respectively. Examination of
      the related enzyme activities showed that the elicitation effect of A13 on LAB
      accumulation correlated with cinnamic acid 4-hydroxylase (C4H) activity in the
      phenylpropanoid pathway under field conditions. Our results confirmed that
      Alternaria sp. A13 not only contributes to the stimulation of S. miltiorrhiza
      root growth, but also boosts the secondary metabolism, thus demonstrating its
      application potential as a bio-fertiliser for S. miltiorrhiza cultivation,
      especially in areas outside of its native growth regions.

PMID- 29337925
TI  - Plant Secondary Metabolites as Anticancer Agents: Successes in Clinical Trials
      and Therapeutic Application.
AB  - Cancer is a multistage process resulting in an uncontrolled and abrupt division
      of cells and is one of the leading causes of mortality. The cases reported and
      the predictions for the near future are unthinkable. Food and Drug Administration
      data showed that 40% of the approved molecules are natural compounds or inspired
      by them, from which, 74% are used in anticancer therapy. In fact, natural
      products are viewed as more biologically friendly, that is less toxic to normal
      cells. In this review, the most recent and successful cases of secondary
      metabolites, including alkaloid, diterpene, triterpene and polyphenolic type
      compounds, with great anticancer potential are discussed. Focusing on the ones
      that are in clinical trial development or already used in anticancer therapy,
      therefore successful cases such as paclitaxel and homoharringtonine (in clinical
      use), curcumin and ingenol mebutate (in clinical trials) will be addressed. Each
      compound's natural source, the most important steps in their discovery, their
      therapeutic targets, as well as the main structural modifications that can
      improve anticancer properties will be discussed in order to show the role of
      plants as a source of effective and safe anticancer drugs.

PMID- 29337928
TI  - Protective Factors in the Inuit Population of Nunavut: A Comparative Study of
      People Who Died by Suicide, People Who Attempted Suicide, and People Who Never
      Attempted Suicide.
AB  - Epidemiological data shows an alarming prevalence of suicide in Aboriginal
      populations around the world. In Canada, the highest rates are found in Inuit
      communities. In this article, we present the findings of a secondary analysis
      conducted with data previously collected as part of a larger study of
      psychological autopsies conducted in Nunavut, Canada. The objective of this
      secondary analysis was to identify protective factors in the Inuit population of
      Nunavut by comparing people who died by suicide, people from the general
      population who attempted suicide, and people from the general population who
      never attempted suicide. This case-control study included 90 participants, with
      30 participants in each group who were paired by birth date, sex, and community.
      Content analysis was first conducted on the clinical vignettes from the initial
      study in order to codify the presence of protective variables. Then, inferential
      analyses were conducted to highlight differences between each group in regards to
      protection. Findings demonstrated that (a) people with no suicide attempt have
      more protective variables throughout their lifespan than people who died by
      suicide and those with suicide attempts within the environmental, social, and
      individual dimensions; (b) people with suicide attempts significantly differ from
      the two other groups in regards to the use of services; and (c) protective
      factors that stem from the environmental dimension show the greatest difference
      between the three groups, being significantly more present in the group with no
      suicide attempt. Considering these findings, interventions could focus on
      enhancing environmental stability in Inuit communities as a suicide prevention
      strategy.

PMID- 29337929
TI  - Integrated Analyses Reveal Overexpressed Notch1 Promoting Porcine Satellite
      Cells' Proliferation through Regulating the Cell Cycle.
AB  - Notch signaling as a conserved cell fate regulator is involved in the regulation
      of cell quiescence, proliferation, differentiation and postnatal tissue
      regeneration. However, how Notch signaling regulates porcine satellite cells
      (PSCs) has not been elucidated. We stably transfected Notch1 intracellular domain
      (N1ICD) into PSCs to analyze the gene expression profile and miRNA-seq. The
      analysis of the gene expression profile identified 295 differentially-expressed
      genes (DEGs) in proliferating-N1ICD PSCs (P-N1ICD) and nine DEGs on
      differentiating-N1ICD PSCs (D-N1ICD), compared with that in control groups (P
      Control and D-Control, respectively). Analyzing the underlying function of DEGs
      showed that most of the upregulated DEGs enriched in P-N1ICD PSCs are related to
      the cell cycle. Forty-four and 12 known differentially-expressed miRNAs (DEMs)
      were identified in the P-N1ICD PSCs and D-N1ICD PSCs group, respectively.
      Furthermore, we constructed the gene-miRNA network of the DEGs and DEMs. In P
      N1ICD PSCs, miR-125a, miR-125b, miR-10a-5p, ssc-miR-214, miR-423 and miR-149 are
      downregulated hub miRNAs, whose corresponding hub genes are marker of
      proliferation Ki-67 (MKI67) and nuclear receptor binding SET domain protein 2
      (WHSC1). By contrast, miR-27a, miR-146a-5p and miR-221-3p are upregulated hub
      miRNAs, whose hub genes are RUNX1 translocation partner 1 (RUNX1T1) and
      fibroblast growth factor 2 (FGF2). All the hub miRNAs and genes are associated
      with cell proliferation. Quantitative RT-PCR results are consistent with the gene
      expression profile and miRNA-seq results. The results of our study provide
      valuable information for understanding the molecular mechanisms underlying Notch
      signaling in PSCs and skeletal muscle development.

PMID- 29337931
TI  - Real Time Spectroscopic Ellipsometry Analysis of First Stage CuIn1-xGaxSe2
      Growth: Indium-Gallium Selenide Co-Evaporation.
AB  - Real time spectroscopic ellipsometry (RTSE) has been applied for in-situ
      monitoring of the first stage of copper indium-gallium diselenide (CIGS) thin
      film deposition by the three-stage co-evaporation process used for fabrication of
      high efficiency thin film photovoltaic (PV) devices. The first stage entails the
      growth of indium-gallium selenide (In1-xGax)2Se3 (IGS) on a substrate of Mo
      coated soda lime glass maintained at a temperature of 400  degrees C. This is a
      critical stage of CIGS deposition because a large fraction of the final film
      thickness is deposited, and as a result precise compositional control is desired
      in order to achieve the optimum performance of the resulting CIGS solar cell.
      RTSE is sensitive to monolayer level film growth processes and can provide
      accurate measurements of bulk and surface roughness layer thicknesses. These in
      turn enable accurate measurements of the bulk layer optical response in the form
      of the complex dielectric function epsilon = epsilon1 - iepsilon2, spectra. Here,
      RTSE has been used to obtain the (epsilon1, epsilon2) spectra at the measurement
      temperature of 400  degrees C for IGS thin films of different Ga contents (x)
      deduced from different ranges of accumulated bulk layer thickness during the
      deposition process. Applying an analytical expression in common for each of the
      (epsilon1, epsilon2) spectra of these IGS films, oscillator parameters have been
      obtained in the best fits and these parameters in turn have been fitted with
      polynomials in x. From the resulting database of polynomial coefficients, the
      (epsilon1, epsilon2) spectra can be generated for any composition of IGS from the
      single parameter, x. The results have served as an RTSE fingerprint for IGS
      composition and have provided further structural information beyond simply
      thicknesses, for example information related to film density and grain size. The
      deduced IGS structural evolution and the (epsilon1, epsilon2) spectra have been
      interpreted as well in relation to observations from scanning electron
      microscopy, X-ray diffractometry and energy-dispersive X-ray spectroscopy
      profiling analyses. Overall the structural, optical and compositional analysis
      possible by RTSE has assisted in understanding the growth and properties of three
      stage CIGS absorbers for solar cells and shows future promise for enhancing cell
      performance through monitoring and control.

PMID- 29337933
TI  - Porpoise-Driven Life.

PMID- 29337930
TI  - Asbestos-Related Disorders in Germany: Background, Politics, Incidence,
      Diagnostics and Compensation.
AB  - There was some limited use of asbestos at end of the 19th century in
      industrialized countries including Germany, but its consumption dramatically
      increased after World War II. The increase in use and exposure was followed by
      the discovery of high numbers of asbestos-related diseases with a mean latency
      period of about 38 years in Germany. The strong socio-political pressure from the
      asbestos industry, its affiliated scientists and physicians has successfully
      hindered regulatory measures and an asbestos ban for many years; a restrictive
      stance that is still being unravelled in compensation litigation. This national
      experience is compared with the situation in other industrialized countries and
      against the backdrop of the constant efforts of the WHO to eliminate asbestos
      related diseases worldwide.

PMID- 29337932
TI  - High Number of Circulating Tumor Cells Predicts Poor Survival of Cutaneous
      Melanoma Patients in China.
AB  - BACKGROUND Melanoma is an aggressive cancer with complex etiology and poor
      prognosis. Surgical resection is still the primary treatment of melanoma, but
      shows limited efficacy in late-stage patients. Additionally, reliable prognostic
      markers of skin melanoma patients are still lacking. Circulating tumor cells
      (CTCs) have shown promise in predicting prognosis of multiple cancers. Evaluating
      the prognostic value of CTC number in melanoma patients. MATERIAL AND METHODS
      CTCs were isolated by immunomagnetic capture from 7.5-mL samples of blood from
      100 patients with cutaneous melanoma. Baseline CTC number (pre-treatment) and
      post-treatment CTC number were measured. Baseline CTC number and CTC number
      alteration were correlated with clinicopathological features and survival.
      RESULTS Forty-three (43%) patients had more than 6 CTCs, whereas 57 (57%) had 6
      cells or less. High baseline CTC count was associated with deep local invasion,
      lymph node metastasis, and distance metastasis, with P value of 0.003, 0.047, and
      0.034, respectively. High baseline CTC count was also correlated with short
      overall survival time and was considered as an independent prognostic factor (P
      value=0.012, hazard ratio=2.262). CTC cell alteration was associated with
      progression-free survival and disease-specific survival (with P values of 0.012
      and 0.009, respectively). CONCLUSIONS Baseline CTC count was correlated with
      adverse pathological features and was predictive of survival in melanoma
      patients. Alteration of CTC count before and after treatment was an indicator of
      therapy response and prognosis. Measuring the baseline and post-treatment CTC
      counts is a powerful tool in monitoring melanoma progression, drug response, and
      survival.

PMID- 29337934
TI  - Depths of Space, Oceans and Politics.

PMID- 29337936
TI  - Recommended.

PMID- 29337935
TI  - Salmon Sex Moves Mountains.

PMID- 29337937
TI  - Bee Sides.

PMID- 29337938
TI  - A Universal Flu Vaccine Is Vital.

PMID- 29337939
TI  - Greener Skies.

PMID- 29337941
TI  - Letters.

PMID- 29337940
TI  - Go Public or Perish.

PMID- 29337942
TI  - Rivers of Plastic.

PMID- 29337943
TI  - Troubled Waters.

PMID- 29337944
TI  - The First Monster Black Holes.

PMID- 29337945
TI  - The End of Night.

PMID- 29337946
TI  - Misled Penguins.

PMID- 29337947
TI  - Guardian Dogs of the Mongolian Steppe.

PMID- 29337948
TI  - [Redacted].

PMID- 29337949
TI  - The Robotic Artist Problem.

PMID- 29337950
TI  - Quick Hits.

PMID- 29337951
TI  - Fruitless Foragers.

PMID- 29337952
TI  - Vanquishing Diabetes.

PMID- 29337953
TI  - Diamond in the Rough.

PMID- 29337954
TI  - Wearable Data.

PMID- 29337955
TI  - Are Smartphones Really Destroying the Adolescent Brain?

PMID- 29337956
TI  - Why Fake Operations Are a Good Thing.

PMID- 29337957
TI  - Moon Shot.

PMID- 29337958
TI  - 50, 100 &150 Years Ago.

PMID- 29337959
TI  - The Tribalism of Truth.

PMID- 29337960
TI  - Alvy's Error and the Meaning of Life.

PMID- 29337961
TI  - How the evolution of multicellularity set the stage for cancer.
AB  - Neoplastic growth and many of the hallmark properties of cancer are driven by the
      disruption of molecular networks established during the emergence of
      multicellularity. Regulatory pathways and molecules that evolved to impose
      regulatory constraints upon networks established in earlier unicellular organisms
      enabled greater communication and coordination between the diverse cell types
      required for multicellularity, but also created liabilities in the form of points
      of vulnerability in the network that when mutated or dysregulated facilitate the
      development of cancer. These factors are usually overlooked in genomic analyses
      of cancer, but understanding where vulnerabilities to cancer lie in the networks
      of multicellular species would provide important new insights into how core
      molecular processes and gene regulation change during tumourigenesis. We describe
      how the evolutionary origins of genes influence their roles in cancer, and how
      connections formed between unicellular and multicellular genes that act as key
      regulatory hubs for normal tissue homeostasis can also contribute to malignant
      transformation when disrupted. Tumours in general are characterised by increased
      dependence on unicellular processes for survival, and major dysregulation of the
      control structures imposed on these processes during the evolution of
      multicellularity. Mounting molecular evidence suggests altered interactions at
      the interface between unicellular and multicellular genes play key roles in the
      initiation and progression of cancer. Furthermore, unicellular network regions
      activated in cancer show high degrees of robustness and plasticity, conferring
      increased adaptability to tumour cells by supporting effective responses to
      environmental pressures such as drug exposure. Examining how the links between
      multicellular and unicellular regions get disrupted in tumours has great
      potential to identify novel drivers of cancer, and to guide improvements to
      cancer treatment by identifying more effective therapeutic strategies. Recent
      successes in targeting unicellular processes by novel compounds underscore the
      logic of such approaches. Further gains could come from identifying genes at the
      interface between unicellular and multicellular processes and manipulating the
      communication between network regions of different evolutionary ages.

PMID- 29337962
TI  - The relationship between right-sided tumour location, tumour microenvironment,
      systemic inflammation, adjuvant therapy and survival in patients undergoing
      surgery for colon and rectal cancer.
AB  - BACKGROUND: There has been an increasing interest in the role of tumour location
      in the treatment and prognosis of patients with colorectal cancer (CRC),
      specifically in the adjuvant setting. Together with genomic data, this has led to
      the proposal that right-sided and left-sided tumours should be considered as
      distinct biological and clinical entities. The aim of the present study was to
      examine the relationship between tumour location, tumour microenvironment,
      systemic inflammatory response (SIR), adjuvant chemotherapy and survival in
      patients undergoing potentially curative surgery for stage I-III colon and rectal
      cancer. METHODS: Clinicopathological characteristics were extracted from a
      prospective database. MMR and BRAF status was determined using
      immunohistochemistry. The tumour microenvironment was assessed using routine H&E
      pathological sections. SIR was assessed using modified Glasgow Prognostic Score
      (mGPS), neutrophil:lymphocyte ratio (NLR), neutrophil:platelet score (NPS) and
      lymphocyte:monocyte ratio (LMR). RESULTS: Overall, 972 patients were included.
      The majority were over 65 years (68%), male (55%), TNM stage II/III (82%). In
      all, 40% of patients had right-sided tumours and 31% had rectal cancers. Right
      sided tumour location was associated with older age (P=0.001), deficient MMR
      (P=0.005), higher T stage (P<0.001), poor tumour differentiation (P<0.001),
      venous invasion (P=0.021), and high CD3+ within cancer cell nests (P=0.048).
      Right-sided location was consistently associated with a high SIR, mGPS (P<0.001)
      and NPS (P<0.001). There was no relationship between tumour location, adjuvant
      chemotherapy (P=0.632) or cancer-specific survival (CSS; P=0.377). In those 275
      patients who received adjuvant chemotherapy, right-sided location was not
      associated with the MMR status (P=0.509) but was associated with higher T stage
      (P=0.001), venous invasion (P=0.036), CD3+ at the invasive margin (P=0.033) and
      CD3+ within cancer nests (P=0.012). There was no relationship between tumour
      location, SIR or CSS in the adjuvant group. CONCLUSIONS: Right-sided tumour
      location was associated with an elevated tumour lymphocytic infiltrate and an
      elevated SIR. There was no association between tumour location and survival in
      the non-adjuvant or adjuvant setting in patients undergoing potentially curative
      surgery for stage I-III colon and rectal cancer.

PMID- 29337964
TI  - Cancer therapy: A path of DSF destruction.

PMID- 29337963
TI  - Phase I open-label study of afatinib plus vinorelbine in patients with solid
      tumours overexpressing EGFR and/or HER2.
AB  - BACKGROUND: This phase Ib study evaluated afatinib plus vinorelbine in patients
      with advanced solid tumours overexpressing epidermal growth factor receptor
      (EGFR) and/or human EGFR 2 (HER2). METHODS: Maximum tolerated doses (MTDs) were
      determined for afatinib (20, 40 or 50 mg, once daily) combined with standard
      intravenous vinorelbine (part A; 25 mg m-2 per week) or oral vinorelbine (part B;
      60 mg m-2 per week, increased to 80 mg m-2 per week at week 3). Secondary end
      points for expanded MTD cohorts included assessments of safety, pharmacokinetics,
      tumour response and progression-free survival (PFS). RESULTS: The afatinib MTD
      was 40 mg with intravenous (MTDA) and oral (MTDB) vinorelbine. The most frequent
      cycle 1 dose-limiting toxicities were febrile neutropenia and diarrhoea,
      consistent with individual safety profiles of vinorelbine and afatinib. Common
      treatment-related adverse events included: diarrhoea (92.7%), asthenia (76.4%),
      nausea (63.6%), neutropenia (56.4%) and vomiting (54.5%). No notable
      pharmacokinetic interactions were observed. Best overall tumour response was
      stable disease in part A (16 out of 28 patients), and partial response in part B
      (3 out of 27 patients). Median PFS was 14.6 and 15.9 weeks for patients treated
      at the MTDA and MTDB, including dose-escalation and expansion cohorts.
      CONCLUSIONS: Afatinib in combination with intravenous or oral vinorelbine
      demonstrated a manageable safety profile and antitumour activity at the MTD of 40
      mg per day.

PMID- 29337965
TI  - Synthetic biology: License to kill.

PMID- 29337966
TI  - Drug development: Allosteric inhibitors hit USP7 hard.

PMID- 29337967
TI  - Errata: Continuous directed evolution of aminoacyl-tRNA synthetases.
AB  - This corrects the article DOI: 10.1038/nchembio.2474.

PMID- 29337968
TI  - RNA Splicing: Making the cut.

PMID- 29337969
TI  - Toward an orthogonal central dogma.

PMID- 29337970
TI  - Cell biology: Eaten up from the inside.

PMID- 29337971
TI  - Plant hormones: Metabolic end run to jasmonate.

PMID- 29337972
TI  - Natural products: Tapping into personalized chemistry.

PMID- 29337973
TI  - Visual perception of the osseous labyrinth rendered from micro-CT scans of the
      petrous bone.
AB  - Grayscale images comparing to the color images may have less of visual
      information necessary for easy recognition of the anatomical structures. Although
      micro-CT scanners deliver images of ultra-high resolution, application of false
      colors to the rendered structures enhance their visual perception and allow for
      quick delineation between them and surrounding bony matrix. This paper presents
      differences of imaging of the osseous structures of the inner ear labyrinth using
      pseudo-color volume rendering in contrast to grayscale volume rendering of the
      micro-CT data. Applied procedures of image processing improved significantly
      delineation between the bony matrix surrounding the cochlea and vestibule
      rendered in the pseudo-colors than in grayscale.

PMID- 29337974
TI  - Ferric reducing ability of plasma and assessment of selected plasma antioxidants
      in adults with celiac disease.
AB  - INTRODUCTION: Oxidative stress with an excessive free radical production and a
      reduction in the activity of protective antioxidants is considered as one of the
      mechanisms responsible for gluten toxicity. However, its role in celiac disease
      (CD) is unclear. OBJECTIVES: Evaluation of plasma nonenzymatic antioxidant
      capacity in patients with CD (both untreated patients and those receiving gluten
      free diet [GFD]) by measuring the ferric reducing ability of plasma (FRAP) as
      well as assessing selected plasma antioxidants. PATIENTS AND METHODS: The study
      included 169 adult patients: 48 patients with untreated active CD, 72 patients
      with CD on a GFD, and 49 healthy controls. In each group, we measured the serum
      levels of selected antioxidants (uric acid, bilirubin, albumin, and vitamin E)
      and used the FRAP assay to assess the total antioxidant capacity (TAC) of plasma.
      In each patient, serological and histopathological activity of CD was also
      evaluated. RESULTS: There were no significant differences in the TAC of plasma
      measured with the FRAP assay between the study groups. Patients with CD had
      higher uric acid levels compared with controls (p <0.001), while bilirubin levels
      were lower in patients with active disease than in controls (p <0.05). Serum
      vitamin E levels were lower in all patients with CD compared with controls (p
      <0.01). CONCLUSIONS: The FRAP assay is not the method of choice for assessing the
      TAC of plasma in patients with CD. Owing to high serum uric acid levels, the FRAP
      assay results in these patients may be overestimated despite the reduced levels
      of other plasma antioxidants.

PMID- 29337975
TI  - Emotional states and sleep disorders in adolescent and young adult cystic
      fibrosis patients.
AB  - The aim of the study was to evaluate level of anxiety, depression and aggression
      and the sleep quality among Polish adolescent and young adult suffering from
      cystic fibrosis including the evaluation of their FEV1. The study involved 70
      patients both male and female aged between 14 and 25 and suffering from cystic
      fibrosis. Anxiety, depression and aggression were evaluated by means of Hospital
      Anxiety and Depression Scale and the quality of sleep was examined following
      Athens Insomnia Scale another aspect taken into consideration was patients' FEV1.
      The data analysis was carried out by means of Chi2, Kolmogorov-Smirnov test,
      Student's t-test, Fisher-Snedecor test, Pearson correlation coeficient. The level
      of statistical significance was set at p <0.05. Anxiety was observed in 27
      (38.6%) cases, depression in 17 (24.3%) and aggression in 46 (65.7%) cases.
      Anxiety (p = 0.017) and aggression (p = 0.004) were significantly higher among
      women than among men. 37 (52.8%) patients reported sleep disorders. The findings
      proved that there is a connection between the quality of sleep and anxiety (r =
      0.631; p = 0.000), depression (r = 0.621; p = 0.000) and aggression (r = 0.293; p
      = 0.014). No significant relationship was found between the quality of sleep and
      patients' expiratory volume. Emotional disorders such as anxiety, depression and
      aggression as well as sleep disorders are commonly reported in patients suffering
      from cystic fibrosis.

PMID- 29337976
TI  - Ludwik Karol Teichmann (1823-1895).
AB  - Ludwik Karol Teichmann was the last of gross anatomists. His magnificent work on
      the lymphatic system gained him appreciation of the whole current scientific
      world. Based on the unpublished materials authors wanted to commemorate one of
      the greatest Polish and world anatomists with special regard to coming soon 150th
      anniversary of Theatrum Anatomicum of Jagiellonian University Medical College.

PMID- 29337977
TI  - Canaliform median raphe cysts (MRCs) lined by squamous epithelium in a 5 year old
      male patient; report of a rare case and comprehensive review of the literature.
AB  - : Median raphe cysts (MRCs) are rare, benign congenital lesions of unknown
      origin, that can be found anywhere on the ventral side of the genital area,
      between the urethral meatus and the anus. The rarity of our case is attributed to
      the canaliform type, the scrotal and perineal localization and the epidermoid
      epithelium. A 5 year old boy, with free perinatal and family history, was
      admitted to our department as an outpatient due to the presence of an elongated
      and mildly painful lesion in the middle of the scrotum, gradually increasing in
      size. During physical examination the presence of a painful, subcutaneous,
      yellowish lesion, extending from the scrotal to the perineal raphe, was
      documented. Patient underwent elective surgery, under general endotracheal
      anesthesia, and complete resection of the lesion was conducted. Histopathological
      examination revealed the presence of a canaliform lesion consisting of five
      cysts, lined by squamous epithelium and filled with lamellate keratin. IN
      CONCLUSION: a) preventive removal of MRCs is considered as the safest treatment
      option, in order to be avoided future, potential complications regarding
      urination and sexual intercourse, b) if therapeutic intervention is delayed,
      especially a er development of inflammation of MRCs, then the likelihood both of
      iatrogenic injury to underlying structures, mainly to the penile or perineal
      urethra, and of relapse a er resection increases significantly and c) if
      orchidopexy precedes the development of MRCs, the possibility of presence of
      ovarian serous border line tumor with Mullerian duct remnants should always be
      excluded.

PMID- 29337978
TI  - Penetration of formaldehyde based fixatives into heart.
AB  - OBJECTIVES: To investigate the penetration depth of formaldehyde-based fixatives
      into cardiac muscle samples over the course of fixation. BACKGROUND: Fixation is
      the essential step in anatomical studies. However, very little is known about
      penetration of most common fixatives into cardiac tissue. METHODS: A total of 40
      heart samples were investigated. 4 study groups (n=10 in each case) were formed
      in such manner they differed only in concentration and type of fixative (1) - 2%
      formaldehyde phosphate-buffered solution (FPBS); (2) - 4% FPBS (formalin); (3) -
      10% FPBS; (4) - alcoholic formalin. Samples were measured before fixation and in
      the following time points: 24 hours, 72 hours, 168 hours. RESULTS: The
      penetration depth differed significantly among studied fixatives (p<0.0001). 100%
      penetration occurred in all samples after 72 hours in alcoholic formalin solution
      and after 168 hours in 10% FPBS. After alcoholic formalin fixation, the tissue is
      more brittle and sub-epicardial blisters were observed in some cases.
      CONCLUSIONS: Alcoholic formalin solution is the fastest fixative among the
      studied ones, however it has several adverse effects on tissue structure. It was
      found that 10% FPBS is the best and a relatively fast fixative for cardiac
      morphometric studies.

PMID- 29337979
TI  - Analysis of pain and painless symptoms in temporomandibular joints dysfunction in
      adult patients.
AB  - : Recent years have shown an increase in the number of patients reporting for
      treatment of pain due to musculoskeletal joint, associated with temporomandibular
      joint dysfunction. Therefore, studies were undertaken, aimed at analyzing the
      symptoms of the dysfunction, because of which patients come to the prosthetic
      treatment. Aim of the thesis: The aim of the study was a retrospective analysis
      of symptoms of temporomandibular joint dysfunction reported by patients diagnosed
      with this problem. MATERIAL AND METHODS: The research material was a
      retrospective medical records of 120 patients, aged 19 to 45 years who have taken
      prosthetic treatment due to temporomandibular joint dysfunction in the Consulting
      Room in Prosthetics Department in Krakow, from June 2015 to December 2016. During
      the test patients, in addition to interviewing a physician, completed a personal
      survey in their own study. The material has been divided into I group of patients
      who reported pain form of dysfunction and II group, who had no symptoms of pain
      within the stomatognatic system. The analysis covered type of symptoms, the share
      of local factors (para-functions) and systemic, as well as the time a er which
      the patients reported for the treatment of functional disorders since the
      appearance of the first symptoms. RESULTS AND CONCLUSIONS: Analysis of the
      research material showed that the main reason for reporting patients was pain in
      one or both temporal joints of significant intensity (5 to 8 in VAS scale,)
      accompanied by acoustic symptoms. A large group of questioners reported problems
      with the range of jaw movement and head and face pain, as well as subjective
      symptoms from the auditory, sight, neck, neck and shoulder areas.

PMID- 29337980
TI  - The quantitative evaluation of the immunohistochemical expression of the
      pituitary adenomas.
AB  - BACKGROUND: The aim of this study was to evaluate morphometrically the pituitary
      adenomas immunoexpression. METHODS: The cases of 72 patients were analyzed, who
      underwent transsphenoidal surgery for pituitary adenomas. Subsequently, the
      immunohistochemical pituitary hormone panel was applied including alpha- subunit
      of the glycoprotein hormones. Immunohistochemical sections were analyzed
      quantitatively with the help of morphometric grid. The percentage rate of the
      immunoexpression was calculated separately for every single hormone. RESULTS: As
      a result, 22 monohormonal adenomas (30.56%), 21 plurihormonal adenomas (29.17%),
      21 immunonegative adenomas (29.17%) and 8 unreliable cases (11.11%) were
      recognized. The immunopositivity for particular hormones was found as follows:
      PRL and GH (25% each), alpha-SU (22.22%), ACTH (13.89%), LH and FSH (12.5% each),
      and TSH (5.56%). An average percentage of immunoexpression in each positive
      staining groups occurred as follows: for PRL - 59.98%, for GH - 53.97%, for ACTH 
      39.21%, for TSH - 25.05%, for LH - 37.3%, for FSH - 54.66%, for alpha-SU -
      45.71. CONCLUSION: The morphometrical method utilizing the immunoexpression index
      introduced in this study provided a very precise recognition of pituitary
      adenomas pathology. This method may limit the subjectivity of a single researcher
      and enable better comparison of the studies. The plurihormonality is a common
      phenomenon, and immunohistochemical staining for all adenohypophyseal hormones is
      obligatory in order to classify pituitary adenomas correctly. The awareness of an
      operating neurosurgeon of the importance of meticulous collecting
      histopathological material, especially in microadenoma cases, has essential
      impact on further neuropathological evaluation and possibility of
      immunohistochemical staining.

PMID- 29337981
TI  - HSV encephalitis: is the insight of the clinician still crucial for the outcome?
AB  - Herpes simplex virus (HSV) encephalitis is an acute infection of the Central
      Nervous System (CNS). During the last two decades its incidence has a ten-fold
      increase, while mortality rate exceeds 70%, if left undiagnosed and thus
      untreated. Clinical manifestations, imaging studies, cerebrospinal fluid (CSF)
      analysis and electroencephalogram (EEG) are the basis of diagnostic approach.
      Even when CSF analysis seems normal, imaging studies are not specific and HSV
      polymerase chain reaction (PCR) test is negative, the clinician should be more
      aggressive, if clinical presentation is indicative for HSV encephalitis, by
      administrating acyclovir early after patient's admission. The aim of this short
      review article, after systematic research of the relevant up to date literature,
      is to emphasize the insight of the clinician as for the early diagnosis and the
      prompt therapeutic intervention, which are crucial for the outcome and vital for
      the affected patient.

PMID- 29337982
TI  - The efficacy of cardiopulmonary resuscitation, in a large city, based on Krakow's
      Emergency Medical Service.
AB  - INTRODUCTION: For many years, one of the biggest challenges of public healthcare
      system, in the European Union are cardiovascular diseases. PURPOSE: The purpose
      of this study was to analyze the variables influencing the specific aspects of
      the chain of survival in a large city. METHODS: Patients included in this study
      had to fulfill all of the following criteria: (1) patient had to experience an
      out-of-hospital cardiac arrest (OHCA), (2) emergency medical team had to initiate
      cardio-pulmonary resuscitation (CPR) at the site of the event. Data were
      collected from the 1st of January to the 31st of December 2004. RESULT: In a time
      period from the 1st of January to the 31st of December 2004 emergency medical
      teams initiated 381 resuscitations. The incidence of OHCA in which CRP was
      initiated was 50 events / 100 000 habitants. Spontaneous circulation was achieved
      in 163 patients (42.8%). Thirty-day after the resuscitation 62 patients (16.3%)
      were alive, and 52 patients (13.6%) were discharged alive from the hospital.
      CONCLUSIONS: Analysis of collected data shows that return of spontaneous
      circulation (ROSC) was achieved in 42.8% of patients, 16.3% survived at least 30
      days following the event, and 13.6% of patients were discharged alive from the
      hospital. These results are similar to findings from different studies conducted
      in Poland.

PMID- 29337983
TI  - Wor1 establishes opaque cell fate through inhibition of the general co-repressor
      Tup1 in Candida albicans.
AB  - The pathogenic fungus Candida albicans can undergo phenotypic switching between
      two heritable states: white and opaque. This phenotypic plasticity facilitates
      its colonization in distinct host niches. The master regulator WOR1 is
      exclusively expressed in opaque phase cells. Positive feedback regulation by Wor1
      on the WOR1 promoter is essential for opaque formation, however the underlying
      mechanism of how Wor1 functions is not clear. Here, we use tandem affinity
      purification coupled with mass spectrometry to identify Wor1-interacting
      proteins. Tup1 and its associated complex proteins are found as the major factors
      associated with Wor1. Tup1 occupies the same regions of the WOR1 promoter as Wor1
      preferentially in opaque cells. Loss of Tup1 is sufficient to induce the opaque
      phase, even in the absence of Wor1. This is the first such report of a bypass of
      Wor1 in opaque formation. These genetic analyses suggest that Tup1 is a key
      repressor of the opaque state, and Wor1 functions via alleviating Tup1 repression
      at the WOR1 promoter. Opaque cells convert to white en masse at 37 degrees C. We
      show that this conversion occurs only in the presence of glycolytic carbon
      sources. The opaque state is stabilized when cells are cultured on non-glycolytic
      carbon sources, even in a MTLa/alpha background. We further show that temperature
      and carbon source affect opaque stability by altering the levels of Wor1 and Tup1
      at the WOR1 promoter. We propose that Wor1 and Tup1 form the core regulatory
      circuit controlling the opaque transcriptional program. This model provides
      molecular insights on how C. albicans adapts to different host signals to undergo
      phenotypic switching for colonization in distinct host niches.

PMID- 29337984
TI  - Anteroposterior axis patterning by early canonical Wnt signaling during
      hemichordate development.
AB  - The Wnt family of secreted proteins has been proposed to play a conserved role in
      early specification of the bilaterian anteroposterior (A/P) axis. This hypothesis
      is based predominantly on data from vertebrate embryogenesis as well as planarian
      regeneration and homeostasis, indicating that canonical Wnt (cWnt) signaling
      endows cells with positional information along the A/P axis. Outside of these
      phyla, there is strong support for a conserved role of cWnt signaling in the
      repression of anterior fates, but little comparative support for a conserved role
      in promotion of posterior fates. We further test the hypothesis by investigating
      the role of cWnt signaling during early patterning along the A/P axis of the
      hemichordate Saccoglossus kowalevskii. We have cloned and investigated the
      expression of the complete Wnt ligand and Frizzled receptor complement of S.
      kowalevskii during early development along with many secreted Wnt modifiers.
      Eleven of the 13 Wnt ligands are ectodermally expressed in overlapping domains,
      predominantly in the posterior, and Wnt antagonists are localized predominantly
      to the anterior ectoderm in a pattern reminiscent of their distribution in
      vertebrate embryos. Overexpression and knockdown experiments, in combination with
      embryological manipulations, establish the importance of cWnt signaling for
      repression of anterior fates and activation of mid-axial ectodermal fates during
      the early development of S. kowalevskii. However, surprisingly, terminal
      posterior fates, defined by posterior Hox genes, are unresponsive to manipulation
      of cWnt levels during the early establishment of the A/P axis at late blastula
      and early gastrula. We establish experimental support for a conserved role of Wnt
      signaling in the early specification of the A/P axis during deuterostome body
      plan diversification, and further build support for an ancestral role of this
      pathway in early evolution of the bilaterian A/P axis. We find strong support for
      a role of cWnt in suppression of anterior fates and promotion of mid-axial fates,
      but we find no evidence that cWnt signaling plays a role in the early
      specification of the most posterior axial fates in S. kowalevskii. This posterior
      autonomy may be a conserved feature of early deuterostome axis specification.

PMID- 29337985
TI  - Increased risk of ischemic heart disease, hypertension, and type 2 diabetes in
      women with previous gestational diabetes mellitus, a target group in general
      practice for preventive interventions: A population-based cohort study.
AB  - BACKGROUND: Gestational diabetes mellitus (GDM) is associated with developing
      type 2 diabetes, but very few studies have examined its effect on developing
      cardiovascular disease. METHODS AND FINDINGS: We conducted a retrospective cohort
      study utilizing a large primary care database in the United Kingdom. From 1
      February 1990 to 15 May 2016, 9,118 women diagnosed with GDM were identified and
      randomly matched with 37,281 control women by age and timing of pregnancy (up to
      3 months). Adjusted incidence rate ratios (IRRs) with 95% confidence intervals
      (CIs) were calculated for cardiovascular risk factors and cardiovascular disease.
      Women with GDM were more likely to develop type 2 diabetes (IRR = 21.96; 95% CI
      18.31-26.34) and hypertension (IRR = 1.85; 95% CI 1.59-2.16) after adjusting for
      age, Townsend (deprivation) quintile, body mass index, and smoking. For ischemic
      heart disease (IHD), the IRR was 2.78 (95% CI 1.37-5.66), and for cerebrovascular
      disease 0.95 (95% CI 0.51-1.77; p-value = 0.87), after adjusting for the above
      covariates and lipid-lowering medication and hypertension at baseline. Follow-up
      screening for type 2 diabetes and cardiovascular risk factors was poor.
      Limitations include potential selective documentation of severe GDM for women in
      primary care, higher surveillance for outcomes in women diagnosed with GDM than
      control women, and a short median follow-up postpartum period, with a small
      number of outcomes for IHD and cerebrovascular disease. CONCLUSIONS: Women
      diagnosed with GDM were at very high risk of developing type 2 diabetes and had a
      significantly increased incidence of hypertension and IHD. Identifying this group
      of women in general practice and targeting cardiovascular risk factors could
      improve long-term outcomes.

PMID- 29337986
TI  - The E2.65A mutation disrupts dynamic binding poses of SB269652 at the dopamine D2
      and D3 receptors.
AB  - The dopamine D2 and D3 receptors (D2R and D3R) are important targets for
      antipsychotics and for the treatment of drug abuse. SB269652, a bitopic ligand
      that simultaneously binds both the orthosteric binding site (OBS) and a secondary
      binding pocket (SBP) in both D2R and D3R, was found to be a negative allosteric
      modulator. Previous studies identified Glu2.65 in the SBP to be a key determinant
      of both the affinity of SB269652 and the magnitude of its cooperativity with
      orthosteric ligands, as the E2.65A mutation decreased both of these parameters.
      However, the proposed hydrogen bond (H-bond) between Glu2.65 and the indole
      moiety of SB269652 is not a strong interaction, and a structure activity
      relationship study of SB269652 indicates that this H-bond may not be the only
      element that determines its allosteric properties. To understand the structural
      basis of the observed phenotype of E2.65A, we carried out molecular dynamics
      simulations with a cumulative length of ~77 MUs of D2R and D3R wild-type and
      their E2.65A mutants bound to SB269652. In combination with Markov state model
      analysis and by characterizing the equilibria of ligand binding modes in
      different conditions, we found that in both D2R and D3R, whereas the
      tetrahydroisoquinoline moiety of SB269652 is stably bound in the OBS, the indole
      2-carboxamide moiety is dynamic and only intermittently forms H-bonds with
      Glu2.65. Our results also indicate that the E2.65A mutation significantly affects
      the overall shape and size of the SBP, as well as the conformation of the N
      terminus. Thus, our findings suggest that the key role of Glu2.65 in mediating
      the allosteric properties of SB269652 extends beyond a direct interaction with
      SB269652, and provide structural insights for rational design of SB269652
      derivatives that may retain its allosteric properties.

PMID- 29337987
TI  - Identification of a noncanonical function for ribose-5-phosphate isomerase A
      promotes colorectal cancer formation by stabilizing and activating beta-catenin
      via a novel C-terminal domain.
AB  - Altered metabolism is one of the hallmarks of cancers. Deregulation of ribose-5
      phosphate isomerase A (RPIA) in the pentose phosphate pathway (PPP) is known to
      promote tumorigenesis in liver, lung, and breast tissues. Yet, the molecular
      mechanism of RPIA-mediated colorectal cancer (CRC) is unknown. Our study
      demonstrates a noncanonical function of RPIA in CRC. Data from the mRNAs of 80
      patients' CRC tissues and paired nontumor tissues and protein levels, as well as
      a CRC tissue array, indicate RPIA is significantly elevated in CRC. RPIA
      modulates cell proliferation and oncogenicity via activation of beta-catenin in
      colon cancer cell lines. Unlike its role in PPP in which RPIA functions within
      the cytosol, RPIA enters the nucleus to form a complex with the adenomatous
      polyposis coli (APC) and beta-catenin. This association protects beta-catenin by
      preventing its phosphorylation, ubiquitination, and subsequent degradation. The C
      terminus of RPIA (amino acids 290 to 311), a region distinct from its enzymatic
      domain, is necessary for RPIA-mediated tumorigenesis. Consistent with results in
      vitro, RPIA increases the expression of beta-catenin and its target genes, and
      induces tumorigenesis in gut-specific promotor-carrying RPIA transgenic
      zebrafish. Together, we demonstrate a novel function of RPIA in CRC formation in
      which RPIA enters the nucleus and stabilizes beta-catenin activity and suggests
      that RPIA might be a biomarker for targeted therapy and prognosis.

PMID- 29337988
TI  - L-arginine supplementation reduces mortality and improves disease outcome in mice
      infected with Trypanosoma cruzi.
AB  - Chagas disease caused by Trypanosoma cruzi is a neglected disease that affects
      about 7 million people in Latin America, recently emerging on other continents
      due to migration. As infection in mice is characterized by depletion of plasma L
      arginine, the effect on infection outcome was tested in mice with or without L
      arginine supplementation and treatment with 1400W, a specific inhibitor of
      inducible nitric oxide synthase (iNOS). We found that levels of L-arginine and
      citrulline were reduced in the heart and plasma of infected mice, whereas levels
      of asymmetric dimethylarginine, an endogenous iNOS inhibitor, were higher.
      Moreover, L-arginine supplementation decreased parasitemia and heart parasite
      burden, improving clinical score and survival. Nitric oxide production in heart
      tissue and plasma was increased by L-arginine supplementation, while
      pharmacological inhibition of iNOS yielded an increase in parasitemia and worse
      clinical score. Interestingly, electrocardiograms improved in mice supplemented
      with L-arginine, suggesting that it modulates infection and heart function and is
      thus a potential biomarker of pathology. More importantly, L-arginine may be
      useful for treating T. cruzi infection, either alone or in combination with other
      antiparasitic drugs.

PMID- 29337989
TI  - Differentially-dimensioned furrow formation by zygotic gene expression and the
      MBT.
AB  - Despite extensive work on the mechanisms that generate plasma membrane furrows,
      understanding how cells are able to dynamically regulate furrow dimensions is an
      unresolved question. Here, we present an in-depth characterization of furrow
      behaviors and their regulation in vivo during early Drosophila morphogenesis. We
      show that the deepening in furrow dimensions with successive nuclear cycles is
      largely due to the introduction of a new, rapid ingression phase (Ingression II).
      Blocking the midblastula transition (MBT) by suppressing zygotic transcription
      through pharmacological or genetic means causes the absence of Ingression II, and
      consequently reduces furrow dimensions. The analysis of compound chromosomes that
      produce chromosomal aneuploidies suggests that multiple loci on the X, II, and
      III chromosomes contribute to the production of differentially-dimensioned
      furrows, and we track the X-chromosomal contribution to furrow lengthening to the
      nullo gene product. We further show that checkpoint proteins are required for
      furrow lengthening; however, mitotic phases of the cell cycle are not strictly
      deterministic for furrow dimensions, as a decoupling of mitotic phases with
      periods of active ingression occurs as syncytial furrow cycles progress. Finally,
      we examined the turnover of maternal gene products and find that this is a minor
      contributor to the developmental regulation of furrow morphologies. Our results
      suggest that cellularization dynamics during cycle 14 are a continuation of
      dynamics established during the syncytial cycles and provide a more nuanced view
      of developmental- and MBT-driven morphogenesis.

PMID- 29337991
TI  - HaSAPPy: A tool for candidate identification in pooled forward genetic screens of
      haploid mammalian cells.
AB  - Haploid cells are increasingly used for screening of complex pathways in animal
      genomes. Hemizygous mutations introduced through viral insertional mutagenesis
      can be directly selected for phenotypic changes. Here we present HaSAPPy a tool
      for analysing sequencing datasets of screens using insertional mutations in large
      pools of haploid cells. Candidate gene prediction is implemented through
      identification of enrichment of insertional mutations after selection by
      simultaneously evaluating several parameters. We have developed HaSAPPy for
      analysis of genetic screens for silencing factors of X chromosome inactivation in
      haploid mouse embryonic stem cells. To benchmark the performance, we further
      analyse several datasets of genetic screens in human haploid cells for which
      candidates have been validated. Our results support the effective candidate
      prediction strategy of HaSAPPy. HaSAPPy is implemented in Python, licensed under
      the MIT license, and is available from https://github.com/gdiminin/HaSAPPy.

PMID- 29337990
TI  - Clustering gene expression time series data using an infinite Gaussian process
      mixture model.
AB  - Transcriptome-wide time series expression profiling is used to characterize the
      cellular response to environmental perturbations. The first step to analyzing
      transcriptional response data is often to cluster genes with similar responses.
      Here, we present a nonparametric model-based method, Dirichlet process Gaussian
      process mixture model (DPGP), which jointly models data clusters with a Dirichlet
      process and temporal dependencies with Gaussian processes. We demonstrate the
      accuracy of DPGP in comparison to state-of-the-art approaches using hundreds of
      simulated data sets. To further test our method, we apply DPGP to published
      microarray data from a microbial model organism exposed to stress and to novel
      RNA-seq data from a human cell line exposed to the glucocorticoid dexamethasone.
      We validate our clusters by examining local transcription factor binding and
      histone modifications. Our results demonstrate that jointly modeling cluster
      number and temporal dependencies can reveal shared regulatory mechanisms. DPGP
      software is freely available online at
      https://github.com/PrincetonUniversity/DP_GP_cluster.

PMID- 29337992
TI  - Outstanding resistance and passivation behaviour of new Fe-Co metal-metal glassy
      alloys in alkaline media.
AB  - The electrochemical behavior of the oxide layers on two metal-metal glassy
      alloys, Fe78Co9Cr10Mo2Al1 (VX9)and Fe49Co49V2 (VX50) (at.%), were studied using
      electrochemical techniques including electrochemical frequency modulation (EFM),
      electrochemical impedance spectroscopy (EIS) and cyclic polarization (CP)
      measurements. The morphology and composition of the alloy surfaces were
      investigated using X-ray photoelectron spectroscopy (XPS), scanning electron
      microscopy (SEM) and atomic force microscopy (AFM). The corrosion rate and
      surface roughness of both alloys increased as the concentration of NaOH in
      aqueous solution was raised. The presence of some protective elements in the
      composition of the alloys led to the formation of a spontaneous passive layer on
      the alloy surface. The higher resistance values of both alloys were associated
      with the magnitude of the dielectric properties of the passive films formed on
      their surfaces. Both alloys are classified as having outstanding resistance to
      corrosion, which results from the formation of a passive film that acts as an
      efficient barrier to corrosion in alkaline solution.

PMID- 29337993
TI  - The impact of ribosomal interference, codon usage, and exit tunnel interactions
      on translation elongation rate variation.
AB  - Previous studies have shown that translation elongation is regulated by multiple
      factors, but the observed heterogeneity remains only partially explained. To
      dissect quantitatively the different determinants of elongation speed, we use
      probabilistic modeling to estimate initiation and local elongation rates from
      ribosome profiling data. This model-based approach allows us to quantify the
      extent of interference between ribosomes on the same transcript. We show that
      neither interference nor the distribution of slow codons is sufficient to explain
      the observed heterogeneity. Instead, we find that electrostatic interactions
      between the ribosomal exit tunnel and specific parts of the nascent polypeptide
      govern the elongation rate variation as the polypeptide makes its initial pass
      through the tunnel. Once the N-terminus has escaped the tunnel, the hydropathy of
      the nascent polypeptide within the ribosome plays a major role in modulating the
      speed. We show that our results are consistent with the biophysical properties of
      the tunnel.

PMID- 29337994
TI  - A reassessment of the Montmaurin-La Niche mandible (Haute Garonne, France) in the
      context of European Pleistocene human evolution.
AB  - We here present a comparative study of the Montmaurin-LN Middle Pleistocene
      mandible (Haute-Garonne, France). This mandible, of which its right and left
      molar series are preserved in situ, was found in La Niche cave (Montmaurin's
      karst system) in 1949, and was first attributed to the 'Mindel-Riss' interglacial
      (= MIS 9 to 11) based on its geological context. Later studies based on
      geological and faunal evidence have attributed the Montmaurin-LN mandible to MIS
      7. Following a detailed morphological and metric comparative study of the
      mandible in the 1970s, it was interpreted in the light of a still limited fossil
      record and the prevailing paradigm back then. Waiting for geochronological
      studies in the forthcoming years, here we review the main morphological and
      metrical features of this mandible and its molars, which have been reassessed in
      the framework of a remarkably enlarged Pleistocene fossil record since the
      mandible was first described, and our current, more in-depth understanding of
      human evolution in Europe. Using a selection of mandibular features with
      potential taxonomic signal we have found that the Montmaurin-LN mandible shares
      only a few derived traits with Neandertals. Our analyses reveal that this
      mandible is more closely related to the ancient specimens from the African and
      Eurasian Early and Middle Pleistocene, particularly due to the presence of
      primitive features of the Homo clade. In contrast, the external morphology of the
      molars is clearly similar to that of Neandertals. The results are assessed in the
      light of the present competing hypotheses used to explain the European hominin
      fossil record.

PMID- 29337995
TI  - Evaluation of a community-based intervention to improve maternal and neonatal
      health service coverage in the most rural and remote districts of Zambia.
AB  - BACKGROUND: A community-based intervention comprising both men and women, known
      as Safe Motherhood Action Groups (SMAGs), was implemented in four of Zambia's
      poorest and most remote districts to improve coverage of selected maternal and
      neonatal health interventions. This paper reports on outcomes in the coverage of
      maternal and neonatal care interventions, including antenatal care (ANC), skilled
      birth attendance (SBA) and postnatal care (PNC) in the study areas. METHODOLOGY:
      Three serial cross-sectional surveys were conducted between 2012 and 2015 among
      1,652 mothers of children 0-5 months of age using a 'before-and-after' evaluation
      design with multi-stage sampling, combining probability proportional to size and
      simple random sampling. Logistic regression and chi-square test for trend were
      used to assess effect size and changes in measures of coverage for ANC, SBA and
      PNC during the intervention. RESULTS: Mothers' mean age and educational status
      were non-differentially comparable at all the three-time points. The odds of
      attending ANC at least four times (aOR 1.63; 95% CI 1.38-1.99) and SBA (aOR 1.72;
      95% CI 1.38-1.99) were at least 60% higher at endline than baseline surveillance.
      A two-fold and four-fold increase in the odds of mothers receiving PNC from an
      appropriate skilled provider (aOR 2.13; 95% CI 1.62-2.79) and a SMAG (aOR 4.87;
      95% CI 3.14-7.54), respectively, were observed at endline. Receiving birth
      preparedness messages from a SMAG during pregnancy (aOR 1.76; 95% CI, 1.20-2.19)
      and receiving ANC from a skilled provider (aOR 4.01; 95% CI, 2.88-5.75) were
      significant predictors for SBA at delivery and PNC. CONCLUSIONS: Strengthening
      community-based action groups in poor and remote districts through the support of
      mothers by SMAGs was associated with increased coverage of maternal and newborn
      health interventions, measured through ANC, SBA and PNC. In remote and
      marginalised settings, where the need is greatest, context-specific and
      innovative task-sharing strategies using community health volunteers can be
      effective in improving coverage of maternal and neonatal services and hold
      promise for better maternal and child survival in poorly-resourced parts of sub
      Saharan Africa.

PMID- 29337996
TI  - Occupational exposure to human Mycobacterium bovis infection: A systematic
      review.
AB  - BACKGROUND: Mycobacterium bovis (M. bovis) is the main causative agent of bovine
      zoonotic tuberculosis. The aim of this systematic review is to highlight the
      occupational exposure to bovine tuberculosis due to M. bovis.
      METHODOLOGY/PRINCIPAL FINDINGS: A computer based literature search was carried
      out to identify papers published between January 2006 and March 2017. "PubMed,
      Cochrane Library and Science Direct" databases were searched systematically.
      Articles presenting the following properties were included: (i) focusing on M.
      bovis; (ii) concerning occupational exposure to bovine tuberculosis. A quality
      assessment was performed after selection of studies. Our search strategy
      identified a total of 3,264 papers of which 29 studies met the inclusion
      criteria. Of the 29 articles, 17 were cross-sectional studies (6 were of high
      quality and scored in the range of 6-7, 11 were of moderate quality and scored in
      the range 3-5), 10 were case reports, and 2 were reviews. Different occupational
      fields exposing to the disease were described: livestock sector, particularly in
      contact with dairy cattle (farmers, veterinaries and assistants, abattoir
      workers) and working in contact with wildlife (hunters, taxidermists).
      CONCLUSIONS: A specific guideline for occupational practitioners taking care of
      employees exposed to bovine tuberculosis is warranted and should be tailored to
      level of exposure. This review was intended to be the first step of such a
      project. Articles were identified from various continents and countries with
      different socio-economic situations, broadening our understanding of the
      worldwide situation. Published data on occupational exposure in developed
      countries are scarce. We had to extrapolate findings from countries with higher
      prevalence of the disease.

PMID- 29337997
TI  - Event based surveillance of Middle East Respiratory Syndrome Coronavirus (MERS-
      CoV) in Bangladesh among pilgrims and travelers from the Middle East: An update
      for the period 2013-2016.
AB  - INTRODUCTION: Every year around 150,000 pilgrims from Bangladesh perform Umrah
      and Hajj. Emergence and continuous reporting of MERS-CoV infection in Saudi
      Arabia emphasize the need for surveillance of MERS-CoV in returning pilgrims or
      travelers from the Middle East and capacity building of health care providers for
      disease containment. The Institute of Epidemiology, Disease Control & Research
      (IEDCR) under the Bangladesh Ministry of Health and Family welfare (MoHFW), is
      responsible for MERS-CoV screening of pilgrims/ travelers returning from the
      Middle East with respiratory illness as part of its outbreak investigation and
      surveillance activities. METHODS: Bangladeshi travelers/pilgrims who returned
      from the Middle East and presented with fever and respiratory symptoms were
      studied over the period from October 2013 to June 2016. Patients with respiratory
      symptoms that fulfilled the WHO MERS-CoV case algorithm were tested for MERS-CoV
      and other respiratory tract viruses. Beside surveillance, case recognition
      training was conducted at multiple levels of health care facilities across the
      country in support of early detection and containment of the disease. RESULTS:
      Eighty one suspected cases tested by real time PCR resulted in zero detection of
      MERS-CoV infection. Viral etiology detected in 29.6% of the cases was
      predominantly influenza A (H1N1 and H3N2), and influenza B infection (22%). Peak
      testing occurred mostly following the annual Hajj season. CONCLUSIONS:
      Respiratory tract infections in travelers/pilgrims returning to Bangladesh from
      the Middle East are mainly due to influenza A and influenza B. Though MERS-CoV
      was not detected in the 81 patients tested, continuous screening and surveillance
      are essential for early detection of MERS-CoV infection and other respiratory
      pathogens to prevent transmissions in hospital settings and within communities.
      Awareness building among healthcare providers will help identify suspected cases.

PMID- 29337998
TI  - Cognitive mechanisms for inferring the meaning of novel signals during
      symbolisation.
AB  - As participants repeatedly interact using graphical signals (as in a game of
      Pictionary), the signals gradually shift from being iconic (or motivated) to
      being symbolic (or arbitrary). The aim here is to test experimentally whether
      this change in the form of the signal implies a concomitant shift in the
      inferential mechanisms needed to understand it. The results show that, during
      early, iconic stages, there is more reliance on creative inferential processes
      associated with insight problem solving, and that the recruitment of these
      cognitive mechanisms decreases over time. The variation in inferential mechanism
      is not predicted by the sign's visual complexity or iconicity, but by its
      familiarity, and by the complexity of the relevant mental representations. The
      discussion explores implications for pragmatics, language evolution, and
      iconicity research.

PMID- 29337999
TI  - A dynamical systems approach for estimating phase interactions between rhythms of
      different frequencies from experimental data.
AB  - Synchronization of neural oscillations as a mechanism of brain function is
      attracting increasing attention. Neural oscillation is a rhythmic neural activity
      that can be easily observed by noninvasive electroencephalography (EEG). Neural
      oscillations show the same frequency and cross-frequency synchronization for
      various cognitive and perceptual functions. However, it is unclear how this
      neural synchronization is achieved by a dynamical system. If neural oscillations
      are weakly coupled oscillators, the dynamics of neural synchronization can be
      described theoretically using a phase oscillator model. We propose an estimation
      method to identify the phase oscillator model from real data of cross-frequency
      synchronized activities. The proposed method can estimate the coupling function
      governing the properties of synchronization. Furthermore, we examine the
      reliability of the proposed method using time-series data obtained from numerical
      simulation and an electronic circuit experiment, and show that our method can
      estimate the coupling function correctly. Finally, we estimate the coupling
      function between EEG oscillation and the speech sound envelope, and discuss the
      validity of these results.

PMID- 29338000
TI  - Progression of the first stage of spontaneous labour: A prospective cohort study
      in two sub-Saharan African countries.
AB  - BACKGROUND: Escalation in the global rates of labour interventions, particularly
      cesarean section and oxytocin augmentation, has renewed interest in a better
      understanding of natural labour progression. Methodological advancements in
      statistical and computational techniques addressing the limitations of pioneer
      studies have led to novel findings and triggered a re-evaluation of current
      labour practices. As part of the World Health Organization's Better Outcomes in
      Labour Difficulty (BOLD) project, which aimed to develop a new labour monitoring
      to-action tool, we examined the patterns of labour progression as depicted by
      cervical dilatation over time in a cohort of women in Nigeria and Uganda who gave
      birth vaginally following a spontaneous labour onset. METHODS AND FINDINGS: This
      was a prospective, multicentre, cohort study of 5,606 women with singleton,
      vertex, term gestation who presented at <= 6 cm of cervical dilatation following
      a spontaneous labour onset that resulted in a vaginal birth with no adverse birth
      outcomes in 13 hospitals across Nigeria and Uganda. We independently applied
      survival analysis and multistate Markov models to estimate the duration of labour
      centimetre by centimetre until 10 cm and the cumulative duration of labour from
      the cervical dilatation at admission through 10 cm. Multistate Markov and
      nonlinear mixed models were separately used to construct average labour curves.
      All analyses were conducted according to three parity groups: parity = 0 (n =
      2,166), parity = 1 (n = 1,488), and parity = 2+ (n = 1,952). We performed
      sensitivity analyses to assess the impact of oxytocin augmentation on labour
      progression by re-examining the progression patterns after excluding women with
      augmented labours. Labour was augmented with oxytocin in 40% of nulliparous and
      28% of multiparous women. The median time to advance by 1 cm exceeded 1 hour
      until 5 cm was reached in both nulliparous and multiparous women. Based on a 95th
      percentile threshold, nulliparous women may take up to 7 hours to progress from 4
      to 5 cm and over 3 hours to progress from 5 to 6 cm. Median cumulative duration
      of labour indicates that nulliparous women admitted at 4 cm, 5 cm, and 6 cm
      reached 10 cm within an expected time frame if the dilatation rate was >= 1
      cm/hour, but their corresponding 95th percentiles show that labour could last up
      to 14, 11, and 9 hours, respectively. Substantial differences exist between
      actual plots of labour progression of individual women and the 'average labour
      curves' derived from study population-level data. Exclusion of women with
      augmented labours from the study population resulted in slightly faster labour
      progression patterns. CONCLUSIONS: Cervical dilatation during labour in the
      slowest-yet-normal women can progress more slowly than the widely accepted
      benchmark of 1 cm/hour, irrespective of parity. Interventions to expedite labour
      to conform to a cervical dilatation threshold of 1 cm/hour may be inappropriate,
      especially when applied before 5 cm in nulliparous and multiparous women.
      Averaged labour curves may not truly reflect the variability associated with
      labour progression, and their use for decision-making in labour management should
      be de-emphasized.

PMID- 29338001
TI  - Modelling the large-scale yellow fever outbreak in Luanda, Angola, and the impact
      of vaccination.
AB  - BACKGROUND: Yellow fever (YF), transmitted via bites of infected mosquitoes, is a
      life-threatening viral disease endemic to tropical and subtropical regions of
      Africa and South America. YF has largely been controlled by widespread national
      vaccination campaigns. Nevertheless, between December 2015 and August 2016, YF
      resurged in Angola, quickly spread and became the largest YF outbreak for the
      last 30 years. Recently, YF resurged again in Brazil (December 2016). Thus, there
      is an urgent need to gain better understanding of the transmission pattern of YF.
      MODEL: The present study provides a refined mathematical model, combined with
      modern likelihood-based statistical inference techniques, to assess and
      reconstruct important epidemiological processes underlying Angola's YF outbreak.
      This includes the outbreak's attack rate, the reproduction number ([Formula: see
      text]), the role of the mosquito vector, the influence of climatic factors, and
      the unusual but noticeable appearance of two-waves in the YF outbreak. The model
      explores actual and hypothetical vaccination strategies, and the impacts of
      possible human reactive behaviors (e.g., response to media precautions).
      FINDINGS: While there were 73 deaths reported over the study period, the model
      indicates that the vaccination campaign saved 5.1-fold more people from death and
      saved from illness 5.6-fold of the observed 941 cases. Delaying the availability
      of the vaccines further would have greatly worsened the epidemic in terms of
      increased cases and deaths. The analysis estimated a mean [Formula: see text] and
      an attack rate of 0.09-0.15% (proportion of population infected) over the whole
      period from December 2015 to August 2016. Our estimated lower and upper bounds of
      [Formula: see text] are in line with previous studies. Unusually, [Formula: see
      text] oscillated in a manner that was "delayed" with the reported deaths. High
      recent number of deaths were associated (followed) with periods of relatively low
      disease transmission and low [Formula: see text], and vice-versa. The time-series
      of Luanda's YF cases suggest the outbreak occurred in two waves, a feature that
      would have become far more prominent had there been no mass vaccination. The
      waves could possibly be due to protective reactive behavioral changes of the
      population affecting the mosquito population. The second wave could well be an
      outcome of the March-April rainfall patterns in the 2016 El Nino year by creating
      ideal conditions for the breeding of the mosquito vectors. The modelling
      framework is a powerful tool for studying future YF epidemic outbreaks, and
      provides a basis for future vaccination campaign evaluations.

PMID- 29338002
TI  - The associations between adult body composition and abdominal adiposity outcomes,
      and relative weight gain and linear growth from birth to age 22 in the Birth to
      Twenty Plus cohort, South Africa.
AB  - BACKGROUND: The growing prevalence of overweight and obesity in low- or middle
      income countries precipitates the need to examine early life predictors of
      adiposity. OBJECTIVES: To examine growth trajectories from birth, and
      associations with adult body composition in the Birth to Twenty Plus Cohort,
      Soweto, South Africa. METHODS: Complete data at year 22 was available for 1088
      participants (536 males and 537 females). Conditional weight and height indices
      were generated indicative of relative rate of growth between years 0-2, 2-5, 5-8,
      8-18, and 18-22. Whole body composition was measured at year 22 (range 21-25
      years) using dual energy x-ray absorptiometry (DXA). Total fat free soft tissue
      mass (FFSTM), fat mass, and abdominal visceral adipose tissue (VAT) and
      subcutaneous adipose tissue (SAT) were recorded. RESULTS: Birth weight was
      positively associated with FFSTM and fat mass at year 22 (beta = 0.11, p<0.01 and
      beta = 0.10, p<0.01 respectively). Relative weight gain from birth to year 22 was
      positively associated with FFSTM, fat mass, VAT, and SAT at year 22. Relative
      linear growth from birth to year 22 was positively associated with FFSTM at year
      22. Relative linear growth from birth to year 2 was positively associated with
      VAT at year 22. Being born small for gestational age and being stunted at age 2
      years were inversely associated with FFSTM at year 22. CONCLUSIONS: The
      importance of optimal birth weight and growth tempos during early life for later
      life body composition, and the detrimental effects of pre- and postnatal growth
      restriction are clear; yet contemporary weight-gain most strongly predicted adult
      body composition. Thus interventions should target body composition trajectories
      during childhood and prevent excessive weight gain in early adulthood.

PMID- 29338004
TI  - Interrupting behaviour: Minimizing decision costs via temporal commitment and low
      level interrupts.
AB  - Ideal decision-makers should constantly assess all sources of information about
      opportunities and threats, and be able to redetermine their choices promptly in
      the face of change. However, perpetual monitoring and reassessment impose
      inordinate sensing and computational costs, making them impractical for animals
      and machines alike. The obvious alternative of committing for extended periods of
      time to limited sensory strategies associated with particular courses of action
      can be dangerous and wasteful. Here, we explore the intermediate possibility of
      making provisional temporal commitments whilst admitting interruption based on
      limited broader observation. We simulate foraging under threat of predation to
      elucidate the benefits of such a scheme. We relate our results to diseases of
      distractibility and roving attention, and consider mechanistic substrates such as
      noradrenergic neuromodulation.

PMID- 29338003
TI  - The prevalence of autosomal dominant polycystic kidney disease (ADPKD): A meta
      analysis of European literature and prevalence evaluation in the Italian province
      of Modena suggest that ADPKD is a rare and underdiagnosed condition.
AB  - BACKGROUND AND OBJECTIVES: ADPKD is erroneously perceived as a not rare
      condition, which is mainly due to the repeated citation of a mistaken
      interpretation of old epidemiological data, as reported in the Dalgaard's work
      (1957). Even if ADPKD is not a common condition, the correct prevalence of ADPKD
      in the general population is uncertain, with a wide range of estimations reported
      by different authors. In this work, we have performed a meta-analysis of
      available epidemiological data in the European literature. Furthermore we
      collected the diagnosis and clinical data of ADPKD in a province in the north of
      Italy (Modena). We describe the point and predicted prevalence of ADPKD, as well
      as the main clinical characteristics of ADPKD in this region. METHODS: We looked
      at the epidemiological data according to specific parameters and criteria in the
      Pubmed, CINAHL, Scopus and Web of Science databases. Data were summarized using
      linear regression analysis. We collected patients' diagnoses in the Province of
      Modena according to accepted clinical criteria and/or molecular analysis.
      Predicted prevalence has been calculated through a logistic regression prediction
      applied to the at-risk population. RESULTS: The average prevalence of ADPKD, as
      obtained from 8 epidemiological studies of sufficient quality, is 2.7: 10,000
      (CI95 = 0.73-4.67). The point prevalence of ADPKD in the province of Modena is
      3.63: 10,000 (CI95 = 3.010-3.758). On the basis of the collected pedigrees and
      identification of the at-risk subjects, the predicted prevalence in the Province
      of Modena is 4.76: 10,000 (CI 95% = 4.109-4.918). CONCLUSION: As identified in
      our study, point prevalence is comparable with the majority of the studies of
      literature, while predicted prevalence (4.76: 10,000) generally appears higher
      than in the previous estimates of the literature, with a few exceptions. Thus,
      this could suggest that undiagnosed ADPKD subjects, as predicted by our approach,
      could be relevant and will most likely require more clinical attention.
      Nevertheless, our estimation, in addition to the averaged ones derived from
      literature, not exceeding the limit of 5:10,000 inhabitants, are compatible with
      the definition of rare disease adopted by the European Medicines Agency and Food
      and Drug Administration.

PMID- 29338006
TI  - A model for cooperative gating of L-type Ca2+ channels and its effects on cardiac
      alternans dynamics.
AB  - In ventricular myocytes, membrane depolarization during the action potential (AP)
      causes synchronous activation of multiple L-type CaV1.2 channels (LTCCs), which
      trigger the release of calcium (Ca2+) from the sarcoplasmic reticulum (SR). This
      results in an increase in intracellular Ca2+ (Cai) that initiates contraction.
      During pulsus alternans, cardiac contraction is unstable, going from weak to
      strong in successive beats despite a constant heart rate. These cardiac alternans
      can be caused by the instability of membrane potential (Vm) due to steep AP
      duration (APD) restitution (Vm-driven alternans), instability of Cai cycling
      (Ca2+-driven alternans), or both, and may be modulated by functional coupling
      between clustered CaV1.2 (e.g. cooperative gating). Here, mathematical analysis
      and computational models were used to determine how changes in the strength of
      cooperative gating between LTCCs may impact membrane voltage and intracellular
      Ca2+ dynamics in the heart. We found that increasing the degree of coupling
      between LTCCs increases the amplitude of Ca2+ currents (ICaL) and prolongs AP
      duration (APD). Increased AP duration is known to promote cardiac alternans, a
      potentially arrhythmogenic substrate. In addition, our analysis shows that
      increasing the strength of cooperative activation of LTCCs makes the coupling of
      Ca2+ on the membrane voltage (Cai->Vm coupling) more positive and destabilizes
      the Vm-Cai dynamics for Vm-driven alternans and Cai-driven alternans, but not for
      quasiperiodic oscillation. These results suggest that cooperative gating of LTCCs
      may have a major impact on cardiac excitation-contraction coupling, not only by
      prolonging APD, but also by altering Cai->Vm coupling and potentially promoting
      cardiac arrhythmias.

PMID- 29338005
TI  - Inferring cell state by quantitative motility analysis reveals a dynamic state
      system and broken detailed balance.
AB  - Cell populations display heterogeneous and dynamic phenotypic states at multiple
      scales. Similar to molecular features commonly used to explore cell
      heterogeneity, cell behavior is a rich phenotypic space that may allow for
      identification of relevant cell states. Inference of cell state from cell
      behavior across a time course may enable the investigation of dynamics of
      transitions between heterogeneous cell states, a task difficult to perform with
      destructive molecular observations. Cell motility is one such easily observed
      cell behavior with known biomedical relevance. To investigate heterogenous cell
      states and their dynamics through the lens of cell behavior, we developed
      Heteromotility, a software tool to extract quantitative motility features from
      timelapse cell images. In mouse embryonic fibroblasts (MEFs), myoblasts, and
      muscle stem cells (MuSCs), Heteromotility analysis identifies multiple motility
      phenotypes within the population. In all three systems, the motility state
      identity of individual cells is dynamic. Quantification of state transitions
      reveals that MuSCs undergoing activation transition through progressive motility
      states toward the myoblast phenotype. Transition rates during MuSC activation
      suggest non-linear kinetics. By probability flux analysis, we find that this MuSC
      motility state system breaks detailed balance, while the MEF and myoblast systems
      do not. Balanced behavior state transitions can be captured by equilibrium
      formalisms, while unbalanced switching between states violates equilibrium
      conditions and would require an external driving force. Our data indicate that
      the system regulating cell behavior can be decomposed into a set of attractor
      states which depend on the identity of the cell, together with a set of
      transitions between states. These results support a conceptual view of cell
      populations as dynamical systems, responding to inputs from signaling pathways
      and generating outputs in the form of state transitions and observable motile
      behaviors.

PMID- 29338007
TI  - Bilateral changes in afterhyperpolarization duration of spinal motoneurones in
      post-stroke patients.
AB  - This paper extends the observations presented in the previously published work on
      the afterhyperpolarization (AHP) duration changes in motoneurones (MNs) on the
      paretic (more affected) side of 11 post-stroke patients by the same analysis on
      the non-paretic (less-affected) side. The estimated AHP duration for patients'
      MNs supplying more-affected muscles was significantly longer than control values
      and the elongation decreased with patient age and disorder duration. For MNs
      supplying less-affected muscles, dependency of AHP duration on age was closer to
      the control data, but the scatter was substantially bigger. However, the AHP
      duration estimate of less-affected MNs tended to be longer than that of controls
      in the short time elapsed since the stroke, and shorter than controls in the long
      time. Our results thus suggest that the spinal MNs on both sides respond to the
      cerebral stroke rapidly with prolongation of AHP duration, which tends to
      normalize with time, in line with functional recovery. This suggestion is in
      concert with the published research on post-stroke changes in brain hemispheres.
      To our knowledge, these dependencies have never been investigated before. Since
      the number of our data was limited, the observed trends should be verified in a
      larger sample of patients and such a verification could take into account the
      suggestions for data analysis that we provide in this paper. Our data are in line
      with the earlier published research on MN firing characteristics post-stroke and
      support the conclusion that the MUs of the muscles at the non-paretic side are
      also affected and cannot be considered a suitable control for the MUs on the
      paretic side.

PMID- 29338008
TI  - Interactions between species introduce spurious associations in microbiome
      studies.
AB  - Microbiota contribute to many dimensions of host phenotype, including disease. To
      link specific microbes to specific phenotypes, microbiome-wide association
      studies compare microbial abundances between two groups of samples. Abundance
      differences, however, reflect not only direct associations with the phenotype,
      but also indirect effects due to microbial interactions. We found that microbial
      interactions could easily generate a large number of spurious associations that
      provide no mechanistic insight. Using techniques from statistical physics, we
      developed a method to remove indirect associations and applied it to the largest
      dataset on pediatric inflammatory bowel disease. Our method corrected the
      inflation of p-values in standard association tests and showed that only a small
      subset of associations is directly linked to the disease. Direct associations had
      a much higher accuracy in separating cases from controls and pointed to
      immunomodulation, butyrate production, and the brain-gut axis as important
      factors in the inflammatory bowel disease.

PMID- 29338009
TI  - Anti-angiogenic drug loaded liposomes: Nanotherapy for early atherosclerotic
      lesions in mice.
AB  - Fumagillin-loaded liposomes were injected into ApoE-KO mice. The animals were
      divided into several groups to test the efficacy of this anti-angiogenic drug for
      early treatment of atherosclerotic lesions. Statistical analysis of the lesions
      revealed a decrease in the lesion size after 5 weeks of treatment.

PMID- 29338010
TI  - Gypsophila bermejoi G. Lopez: A possible case of speciation repressed by
      bioclimatic factors.
AB  - Gypsophila bermejoi G. Lopez is an allopolyploid species derived from the
      parental G. struthium L. subsp. struthium and G. tomentosa L. All these plants
      are gypsophytes endemic to the Iberian Peninsula of particular ecological,
      evolutionary and biochemical interest. In this study, we present evidence of a
      possible repression on the process of G. bermejoi speciation by climatic factors.
      We modelled the ecological niches of the three taxa considered here using a
      maximum entropy approach and employing a series of bioclimatic variables.
      Subsequently, we projected these models onto the geographical space of the
      Iberian Peninsula in the present age and at two past ages: the Last Glacial
      Maximum and the mid-Holocene period. Furthermore, we compared these niches using
      the statistical method devised by Warren to calculate their degree of overlap. We
      also evaluated the evolution of the bioclimatic habitat suitability at those
      sites were the soil favors the growth of these species. Both the maximum entropy
      model and the degree of overlap indicated that the ecological behavior of the
      hybrid differs notably from that of the parental species. During the Last Glacial
      Maximum, the two parental species appear to take refuge in the western coastal
      strip of the Peninsula, a region in which there are virtually no sites where G.
      bermejoi could potentially be found. However, in the mid-Holocene period the
      suitability of G. bermejoi to sites with favorable soils shifts from almost null
      to a strong adaptation, a clear change in this tendency. These results suggest
      that the ecological niches of hybrid allopolyploids can be considerably different
      to those of their parental species, which may have evolutionary and ecologically
      relevant consequences. The data obtained indicate that certain bioclimatic
      variables may possibly repress the processes by which new species are formed. The
      difference in the ecological niche of G. bermejoi with respect to its parental
      species prevented it from prospering during the Last Glacial Maximum. However,
      the climatic change in the mid-Holocene period released this block and as such,
      it permitted the new species to establish itself. Accordingly, we favor a recent
      origin of the current populations of G. bermejoi.

PMID- 29338011
TI  - Validation of Growth Layer Group (GLG) depositional rate using daily incremental
      growth lines in the dentin of beluga (Delphinapterus leucas (Pallas, 1776))
      teeth.
AB  - Counts of Growth Layer Groups (GLGs) in the dentin of marine mammal teeth are
      widely used as indicators of age. In most marine mammals, observations document
      that GLGs are deposited yearly, but in beluga whales, some studies have supported
      the view that two GLGs are deposited each year. Our understanding of beluga life
      history differs substantially depending on assumptions regarding the timing of
      GLG deposition; therefore, resolving this issue has important considerations for
      population assessments. In this study, we used incremental lines that represent
      daily pulses of dentin mineralization to test the hypothesis that GLGs in beluga
      dentin are deposited on a yearly basis. Our estimate of the number of daily
      growth lines within one GLG is remarkably close to 365 days within error,
      supporting the hypothesis that GLGs are deposited annually in beluga. We show
      that measurement of daily growth increments can be used to validate the time
      represented by GLGs in beluga. Furthermore, we believe this methodology may have
      broader applications to age estimation in other taxa.

PMID- 29338013
TI  - Dynamical networks of influence in small group discussions.
AB  - In many domains of life, business and management, numerous problems are addressed
      by small groups of individuals engaged in face-to-face discussions. While
      research in social psychology has a long history of studying the determinants of
      small group performances, the internal dynamics that govern a group discussion
      are not yet well understood. Here, we rely on computational methods based on
      network analyses and opinion dynamics to describe how individuals influence each
      other during a group discussion. We consider the situation in which a small group
      of three individuals engages in a discussion to solve an estimation task. We
      propose a model describing how group members gradually influence each other and
      revise their judgments over the course of the discussion. The main component of
      the model is an influence network-a weighted, directed graph that determines the
      extent to which individuals influence each other during the discussion. In
      simulations, we first study the optimal structure of the influence network that
      yields the best group performances. Then, we implement a social learning process
      by which individuals adapt to the past performance of their peers, thereby
      affecting the structure of the influence network in the long run. We explore the
      mechanisms underlying the emergence of efficient or maladaptive networks and show
      that the influence network can converge towards the optimal one, but only when
      individuals exhibit a social discounting bias by downgrading the relative
      performances of their peers. Finally, we find a late-speaker effect, whereby
      individuals who speak later in the discussion are perceived more positively in
      the long run and are thus more influential. The numerous predictions of the model
      can serve as a basis for future experiments, and this work opens research on
      small group discussion to computational social sciences.

PMID- 29338012
TI  - Using geospatial techniques to develop an emergency referral transport system for
      suspected sepsis patients in Bangladesh.
AB  - BACKGROUND: A geographic information system (GIS)-based transport network within
      an emergency referral system can be the key to reducing health system delays and
      increasing the chances of survival, especially during an emergency. We employed a
      GIS to design an emergency transport system for the rapid transfer of pregnant or
      early post-partum women, newborns, and children under 5 years of age with
      suspected sepsis under the Interrupting Pathways to Sepsis Initiative (IPSI)
      project. METHODS: A GIS database was developed by mapping the villages, roads,
      and relevant physical features of the study area. A travel-time algorithm was
      developed to incorporate the time taken by different modes of local transport to
      reach the health complexes. These were used in a network analysis to identify the
      shortest routes to the hospitals from the villages, which were categorized into
      green, yellow, and red zones based on their proximity to the nearest hospitals to
      provide transport facilities. An emergency call-in centre established for the
      project managed the transport system, and its data was used to assess the uptake
      of this transport system amongst distant communities. RESULTS: Fifteen pre
      existing and two new routes were identified as the shortest routes to the health
      complexes. The call-in centre personnel used this route information to direct
      both patients and transport drivers to the nearest transport hubs or pick-up
      points. Adherence with referral advice was high in areas where the IPSI transport
      operated. Over the study period, the utilisation of the project's transport
      doubled and referral compliance from distant zones similarly increased.
      CONCLUSIONS: The GIS system created for this study facilitated rapid referral of
      patients in emergency from distant zones, using locally available transport and
      resources. The methodology described in this study to develop and implement an
      emergency transport system can be applied in similar, rural, low-income country
      settings.

PMID- 29338014
TI  - Value of adding the renal pathological score to the kidney failure risk equation
      in advanced diabetic nephropathy.
AB  - BACKGROUND: There have been a limited number of biopsy-based studies on diabetic
      nephropathy, and therefore the clinical importance of renal biopsy in patients
      with diabetes in late-stage chronic kidney disease (CKD) is still debated. We
      aimed to clarify the renal prognostic value of pathological information to
      clinical information in patients with diabetes and advanced CKD. METHODS: We
      retrospectively assessed 493 type 2 diabetics with biopsy-proven diabetic
      nephropathy in four centers in Japan. 296 patients with stage 3-5 CKD at the time
      of biopsy were identified and assigned two risk prediction scores for end-stage
      renal disease (ESRD): the Kidney Failure Risk Equation (KFRE, a score composed of
      clinical parameters) and the Diabetic Nephropathy Score (D-score, a score
      integrated pathological parameters of the Diabetic Nephropathy Classification by
      the Renal Pathology Society (RPS DN Classification)). They were randomized 2:1 to
      development and validation cohort. Hazard Ratios (HR) of incident ESRD were
      reported with 95% confidence interval (CI) of the KFRE, D-score and KFRE+D-score
      in Cox regression model. Improvement of risk prediction with the addition of D
      score to the KFRE was assessed using c-statistics, continuous net
      reclassification improvement (NRI), and integrated discrimination improvement
      (IDI). RESULTS: During median follow-up of 1.9 years, 194 patients developed
      ESRD. The cox regression analysis showed that the KFRE,D-score and KFRE+D-score
      were significant predictors of ESRD both in the development cohort and in the
      validation cohort. The c-statistics of the D-score was 0.67. The c-statistics of
      the KFRE was good, but its predictive value was weaker than that in the
      miscellaneous CKD cohort originally reported (c-statistics, 0.78 vs. 0.90) and
      was not significantly improved by adding the D-score (0.78 vs. 0.79, p = 0.83).
      Only continuous NRI was positive after adding the D-score to the KFRE (0.4%; CI:
      0.0-0.8%). CONCLUSIONS: We found that the predict values of the KFRE and the D
      score were not as good as reported, and combining the D-score with the KFRE did
      not significantly improve prediction of the risk of ESRD in advanced diabetic
      nephropathy. To improve prediction of renal prognosis for advanced diabetic
      nephropathy may require different approaches with combining clinical and
      pathological parameters that were not measured in the KFRE and the RPS DN
      Classification.

PMID- 29338015
TI  - Exercise-induced circulating microRNA changes in athletes in various training
      scenarios.
AB  - BACKGROUND: The aim of the study was to compare selected extracellular miRNA
      levels (miR-16, miR-21, miR-93 and miR-222 with the response to 8-week-long
      explosive strength training (EXPL), hypertrophic strength training (HYP) and high
      intensity interval training (HIIT). METHODS: 30 young male athletes of white
      European origin (mean age: 22.5 +/- 4.06 years) recruited at the Faculty of
      Sports Studies of Masaryk University were enrolled in this study. The study
      participants were randomly assigned to three possible training scenarios: EXPL,
      HYP or HITT and participated in 8-week-long program in given arm. Blood plasma
      samples were collected at the baseline and at week 5 and 8 and anthropometric and
      physical activity parameters were measured. Pre- and post-intervention
      characteristics were compared and participants were further evaluated as
      responders (RES) or non-responders (NRES). RES/NRES status was established for
      the following characteristics: 300 degrees /s right leg extension (t300), 60
      degrees /s right leg extension (t60), isometric extension (IE), vertical jump,
      isometric extension of the right leg and body fat percentage (BFP). RESULTS: No
      differences in miRNA levels were apparent between the intervention groups at
      baseline. No statistically significant prediction role was observed using crude
      univariate stepwise regression model analysis where RES/NRES status for t300,
      t60, IE, vertical jump and pFM was used as a dependent variable and miR-21, miR
      222, miR-16 and miR-93 levels at baseline were used as independent variables. The
      baseline levels of miR-93 expressed an independent prediction role for responder
      status based on isometric extension of the right leg (beta estimate 0.76, 95% CI:
      -0.01; 1.53, p = 0.052). DISCUSSION: The results of the study indicate that 8
      week-long explosive strength training, hypertrophic strength training and high
      intensity interval training regimens are associated with significant changes in
      miR-16, mir-21, miR-222 and miR-93 levels compared to a baseline in athletic
      young men.

PMID- 29338016
TI  - Ultrasound-mediated delivery and distribution of polymeric nanoparticles in the
      normal brain parenchyma of a metastatic brain tumour model.
AB  - The treatment of brain diseases is hindered by the blood-brain barrier (BBB)
      preventing most drugs from entering the brain. Focused ultrasound (FUS) with
      microbubbles can open the BBB safely and reversibly. Systemic drug injection
      might induce toxicity, but encapsulation into nanoparticles reduces accumulation
      in normal tissue. Here we used a novel platform based on poly(2-ethyl-butyl
      cyanoacrylate) nanoparticle-stabilized microbubbles to permeabilize the BBB in a
      melanoma brain metastasis model. With a dual-frequency ultrasound transducer
      generating FUS at 1.1 MHz and 7.8 MHz, we opened the BBB using nanoparticle
      microbubbles and low-frequency FUS, and applied high-frequency FUS to generate
      acoustic radiation force and push nanoparticles through the extracellular matrix.
      Using confocal microscopy and image analysis, we quantified nanoparticle
      extravasation and distribution in the brain parenchyma. We also evaluated
      haemorrhage, as well as the expression of P-glycoprotein, a key BBB component.
      FUS and microbubbles distributed nanoparticles in the brain parenchyma, and the
      distribution depended on the extent of BBB opening. The results from acoustic
      radiation force were not conclusive, but in a few animals some effect could be
      detected. P-glycoprotein was not significantly altered immediately after
      sonication. In summary, FUS with our nanoparticle-stabilized microbubbles can
      achieve accumulation and displacement of nanoparticles in the brain parenchyma.

PMID- 29338017
TI  - Comparative genomics identifies distinct lineages of S. Enteritidis from
      Queensland, Australia.
AB  - Salmonella enterica is a major cause of gastroenteritis and foodborne illness in
      Australia where notification rates in the state of Queensland are the highest in
      the country. S. Enteritidis is among the five most common serotypes reported in
      Queensland and it is a priority for epidemiological surveillance due to concerns
      regarding its emergence in Australia. Using whole genome sequencing, we have
      analysed the genomic epidemiology of 217 S. Enteritidis isolates from Queensland,
      and observed that they fall into three distinct clades, which we have
      differentiated as Clades A, B and C. Phage types and MLST sequence types differed
      between the clades and comparative genomic analysis has shown that each has a
      unique profile of prophage and genomic islands. Several of the phage regions
      present in the S. Enteritidis reference strain P125109 were absent in Clades A
      and C, and these clades also had difference in the presence of pathogenicity
      islands, containing complete SPI-6 and SPI-19 regions, while P125109 does not.
      Antimicrobial resistance markers were found in 39 isolates, all but one of which
      belonged to Clade B. Phylogenetic analysis of the Queensland isolates in the
      context of 170 international strains showed that Queensland Clade B isolates
      group together with the previously identified global clade, while the other two
      clades are distinct and appear largely restricted to Australia. Locally sourced
      environmental isolates included in this analysis all belonged to Clades A and C,
      which is consistent with the theory that these clades are a source of locally
      acquired infection, while Clade B isolates are mostly travel related.

PMID- 29338019
TI  - Survey of checkpoints along the pathway to diverse biomedical research faculty.
AB  - There is a persistent shortage of underrepresented minority (URM) faculty who are
      involved in basic biomedical research at medical schools. We examined the entire
      training pathway of potential candidates to identify the points of greatest loss.
      Using a range of recent national data sources, including the National Science
      Foundation's Survey of Earned Doctorates and Survey of Doctoral Recipients, we
      analyzed the demographics of the population of interest, specifically those from
      URM backgrounds with an interest in biomedical sciences. We examined the URM
      population from high school graduates through undergraduate, graduate, and
      postdoctoral training as well as the URM population in basic science tenure track
      faculty positions at medical schools. We find that URM and non-URM trainees are
      equally likely to transition into doctoral programs, to receive their doctoral
      degree, and to secure a postdoctoral position. However, the analysis reveals that
      the diversions from developing a faculty career are found primarily at two
      clearly identifiable places, specifically during undergraduate education and in
      transition from postdoctoral fellowship to tenure track faculty in the basic
      sciences at medical schools. We suggest focusing additional interventions on
      these two stages along the educational pathway.

PMID- 29338018
TI  - Oral mucosa tissue gene expression profiling before, during, and after radiation
      therapy for tonsil squamous cell carcinoma.
AB  - BACKGROUND: Radiation-therapy (RT) induces mucositis, a clinically challenging
      condition with limited prophylactic interventions and no predictive tests. In
      this pilot study, we applied global gene-expression analysis on serial human oral
      mucosa tissue and blood cells from patients with tonsil squamous cell cancer
      (TSCC) to identify genes involved in mucositis pathogenesis. METHODS AND
      FINDINGS: Eight patients with TSCC each provided consecutive buccal biopsies and
      blood cells before, after 7 days of RT treatment, and 20 days following RT. We
      monitored clinical mucositis and performed gene-expression analysis on tissue
      samples. We obtained control tissue from nine healthy individuals. After RT,
      expression was upregulated in apoptosis inducer and inhibitor genes, EDA2R and
      MDM2, and in POLH, a DNA-repair polymerase. Expression was downregulated in six
      members of the histone cluster family, e.g., HIST1H3B. Gene expression related to
      proliferation and differentiation was altered, including MKI67 (downregulated),
      which encodes the Ki-67-proliferation marker, and KRT16 (upregulated), which
      encodes keratin16. These alterations were not associated with the clinical
      mucositis grade. However, the expression of LY6G6C, which encodes a surface
      immunoregulatory protein, was upregulated before treatment in three cases of
      clinical none/mild mucositis, but not in four cases of ulcerative mucositis.
      CONCLUSION: RT caused molecular changes related to apoptosis, DNA-damage, DNA
      repair, and proliferation without a correlation to the severity of clinical
      mucositis. LY6G6C may be a potential protective biomarker for ulcerative
      mucositis. Based on these results, our study model of consecutive human biopsies
      will be useful in designing a prospective clinical validation trial to
      characterize molecular mucositis and identify predictive biomarkers.

PMID- 29338020
TI  - Autonomic stress reactivity and craving in individuals with problematic Internet
      use.
AB  - The link between autonomic stress reactivity and subjective urge/craving has been
      less systematically examined in behavioral addictions (i.e. problematic Internet
      use) than in substance use disorders. The present study investigated whether
      problematic Internet users (PU) show enhanced autonomic stress reactivity than
      non-PU, indexed by lower Heart Rate Variability (HRV) and higher Skin Conductance
      Level (SCL) reactivity during the Trier Social Stress Test (TSST), whether
      greater reactivity is related to stronger Internet craving, and whether
      problematic Internet usage is associated with some dysfunctional psychological
      features. Based on their Internet Addiction Test scores, participants were
      divided into PU (N = 24) and non-PU (N = 21). Their heart rate and skin
      conductance were continuously recorded during baseline, social stressors, and
      recovery. Craving for Internet usage were collected using a Likert scale before
      and after the TSST. The SDNN, an overall measure of HRV, was significantly lower
      in PU than non-PU during baseline, but not during and after stressful task.
      Furthermore, only among PU a significant negative correlation emerged between
      SDNN during recovery and craving ratings after the test. No group differences
      emerged for SCL. Lastly, PU endorsed more mood, obsessive-compulsive, and alcohol
      related problems. Our findings suggest that problems in controlling one's use of
      the Internet may be related to reduced autonomic balance at rest. Moreover, our
      results provide new insights into the characterization of craving in PIU,
      indicating the existence of a relationship between craving for Internet usage and
      reduced autonomic flexibility.

PMID- 29338021
TI  - Coral physiology and microbiome dynamics under combined warming and ocean
      acidification.
AB  - Rising seawater temperature and ocean acidification threaten the survival of
      coral reefs. The relationship between coral physiology and its microbiome may
      reveal why some corals are more resilient to these global change conditions.
      Here, we conducted the first experiment to simultaneously investigate changes in
      the coral microbiome and coral physiology in response to the dual stress of
      elevated seawater temperature and ocean acidification expected by the end of this
      century. Two species of corals, Acropora millepora containing the thermally
      sensitive endosymbiont C21a and Turbinaria reniformis containing the thermally
      tolerant endosymbiont Symbiodinium trenchi, were exposed to control (26.5 degrees
      C and pCO2 of 364 MUatm) and treatment (29.0 degrees C and pCO2 of 750 MUatm)
      conditions for 24 days, after which we measured the microbial community
      composition. These microbial findings were interpreted within the context of
      previously published physiological measurements from the exact same corals in
      this study (calcification, organic carbon flux, ratio of photosynthesis to
      respiration, photosystem II maximal efficiency, total lipids, soluble animal
      protein, soluble animal carbohydrates, soluble algal protein, soluble algal
      carbohydrate, biomass, endosymbiotic algal density, and chlorophyll a). Overall,
      dually stressed A. millepora had reduced microbial diversity, experienced large
      changes in microbial community composition, and experienced dramatic
      physiological declines in calcification, photosystem II maximal efficiency, and
      algal carbohydrates. In contrast, the dually stressed coral T. reniformis
      experienced a stable and more diverse microbiome community with minimal
      physiological decline, coupled with very high total energy reserves and
      particulate organic carbon release rates. Thus, the microbiome changed and
      microbial diversity decreased in the physiologically sensitive coral with the
      thermally sensitive endosymbiotic algae but not in the physiologically tolerant
      coral with the thermally tolerant endosymbiont. Our results confirm recent
      findings that temperature-stress tolerant corals have a more stable microbiome,
      and demonstrate for the first time that this is also the case under the dual
      stresses of ocean warming and acidification. We propose that coral with a stable
      microbiome are also more physiologically resilient and thus more likely to
      persist in the future, and shape the coral species diversity of future reef
      ecosystems.

PMID- 29338023
TI  - Traditional agricultural practices and the sex ratio today.
AB  - We study the historical origins of cross-country differences in the male-to
      female sex ratio. Our analysis focuses on the use of the plough in traditional
      agriculture. In societies that did not use the plough, women tended to
      participate in agriculture as actively as men. By contrast, in societies that
      used the plough, men specialized in agricultural work, due to the physical
      strength needed to pull the plough or control the animal that pulls it. We
      hypothesize that this difference caused plough-using societies to value boys more
      than girls. Today, this belief is reflected in male-biased sex ratios, which
      arise due to sex-selective abortion or infanticide, or gender-differences in
      access to family resources, which results in higher mortality rates for girls.
      Testing this hypothesis, we show that descendants of societies that traditionally
      practiced plough agriculture today have higher average male-to-female sex ratios.
      We find that this effect systematically increases in magnitude and statistical
      significance as one looks at older cohorts. Estimates using instrumental
      variables confirm our findings from multivariate OLS analysis.

PMID- 29338022
TI  - Bone metabolism dynamics in the early post-transplant period following kidney and
      liver transplantation.
AB  - Bone disease contributes to relevant morbidity after solid organ transplantation.
      Vitamin D has a crucial role for bone metabolism. Activation of vitamin D depends
      on the endocrine function of both, liver and kidney. Our study assessed key
      markers of bone metabolism at time of transplantation and 6 months after
      transplantation among 70 kidney and 70 liver recipients. In 70 kidney recipients
      25-OH vitamin D levels did not differ significantly between peri-transplant
      (median 32.5nmol/l) and 6 months post-transplant (median 41.9nmol/l; P = 0.272).
      Six months post-transplant median 1, 25-(OH)2 vitamin D levels increased by >300%
      (from 9.1 to 36.5ng/l; P<0.001) and median intact parathyroid hormone levels
      decreased by 68.4% (from 208.7 to 66.0 ng/l; P<0.001). Median beta-Crosslaps
      (CTx) and total procollagen type 1 amino-terminal propeptide (P1NP) decreased by
      65.1% (from 1.32 to 0.46ng/ml; P<0.001) and 60.6% (from 158.2 to 62.3ng/ml;
      P<0.001), respectively. Kidney recipients with incident fractures had
      significantly lower levels of 1, 25-(OH)2 vitamin D at time of transplantation
      and of intact parathyroid hormone 6 months post-transplant. Among 70 liver
      recipients, 25-OH vitamin D, 1, 25-(OH)2 vitamin D and intact parathyroid hormone
      levels were not significantly altered between peri-transplant and 6 months post
      transplant. Contrary to kidney recipients, median CTx increased by 60.0% (from
      0.45 to 0.72 ng/ml; P = 0.002) and P1NP by 49.3% (from 84.0 to 125.4ng/ml; P =
      0.001) in the longitudinal course. Assessed biomarkers didn't differ between
      liver recipients with and without fractures. To conclude, the assessed panel of
      biomarkers proved highly dynamic after liver as well as kidney transplantation in
      the early post-transplant period. After kidney transplantation a significant gain
      in 1, 25-(OH)2 vitamin D combined with a decline in iPTH, CTx and P1NP, whereas
      after liver transplantation an increase in CTx and P1NP were characteristic.

PMID- 29338024
TI  - Quantitative in vivo mapping of myocardial mitochondrial membrane potential.
AB  - BACKGROUND: Mitochondrial membrane potential (DeltaPsim) arises from normal
      function of the electron transport chain. Maintenance of DeltaPsim within a
      narrow range is essential for mitochondrial function. Methods for in vivo
      measurement of DeltaPsim do not exist. We use 18F-labeled tetraphenylphosphonium
      (18F-TPP+) to measure and map the total membrane potential, DeltaPsiT, as the sum
      of DeltaPsim and cellular (DeltaPsic) electrical potentials. METHODS: Eight pigs,
      five controls and three with a scar-like injury, were studied. Pigs were studied
      with a dynamic PET scanning protocol to measure 18F-TPP+ volume of distribution,
      VT. Fractional extracellular space (fECS) was measured in 3 pigs. We derived
      equations expressing DeltaPsiT as a function of VT and the volume-fractions of
      mitochondria and fECS. Seventeen segment polar maps and parametric images of
      DeltaPsiT were calculated in millivolts (mV). RESULTS: In controls, mean
      segmental DeltaPsiT = -129.4+/-1.4 mV (SEM). In pigs with segmental tissue
      injury, DeltaPsiT was clearly separated from control segments but variable, in
      the range -100 to 0 mV. The quality of DeltaPsiT maps was excellent, with low
      noise and good resolution. Measurements of DeltaPsiT in the left ventricle of
      pigs agree with previous in in-vitro measurements. CONCLUSIONS: We have analyzed
      the factors affecting the uptake of voltage sensing tracers and developed a
      minimally invasive method for mapping DeltaPsiT in left ventricular myocardium of
      pigs. DeltaPsiT is computed in absolute units, allowing for visual and
      statistical comparison of individual values with normative data. These studies
      demonstrate the first in vivo application of quantitative mapping of total tissue
      membrane potential, DeltaPsiT.

PMID- 29338025
TI  - Adolescent cohorts assessing growth, cardiovascular and cognitive outcomes in low
      and middle-income countries.
AB  - INTRODUCTION: Life-course studies are needed to explore how exposures during
      adolescence, particularly puberty, contribute to later cardiovascular risk and
      cognitive health in low and middle-income countries (LMIC), where 90% of the
      world's young people live. The extent of any existing cohorts investigating these
      outcomes in LMIC has not previously been described. METHODS: We performed a
      systematic literature review to identify population cohort studies of adolescents
      in LMIC that assessed anthropometry and any of cardiovascular risk (blood
      pressure, physical activity, plasma glucose/lipid profile and substance misuse),
      puberty (age at menarche, Tanner staging, or other form of pubertal staging) or
      cognitive outcomes. Studies that recruited participants on the basis of a pre
      existing condition or involved less than 500 young people were excluded.
      FINDINGS: 1829 studies were identified, and 24 cohorts fulfilled inclusion
      criteria based in Asia (10), Africa (6) and South / Central America (8). 14 (58%)
      of cohorts identified were based in one of four countries; India, Brazil, Vietnam
      or Ethiopia. Only 2 cohorts included a comprehensive cardiovascular assessment,
      tanner pubertal staging, and cognitive outcomes. CONCLUSION: Improved utilisation
      of existing datasets and additional cohort studies of adolescents in LMIC that
      collect contemporaneous measures of growth, cognition, cardiovascular risk and
      pubertal development are needed to better understand how this period of the life
      course influences future non-communicable disease morbidity and cognitive
      outcomes.

PMID- 29338026
TI  - Flow cytometric analysis identifies changes in S and M phases as novel cell cycle
      alterations induced by the splicing inhibitor isoginkgetin.
AB  - The spliceosome is a large ribonucleoprotein complex that catalyzes the removal
      of introns from RNA polymerase II-transcribed RNAs. Spliceosome assembly occurs
      in a stepwise manner through specific intermediates referred to as pre
      spliceosome complexes E, A, B, B* and C. It has been reported that small molecule
      inhibitors of the spliceosome that target the SF3B1 protein component of complex
      A lead to the accumulation of cells in the G1 and G2/M phases of the cell cycle.
      Here we performed a comprehensive flow cytometry analysis of the effects of
      isoginkgetin (IGG), a natural compound that interferes with spliceosome assembly
      at a later step, complex B formation. We found that IGG slowed cell cycle
      progression in multiple phases of the cell cycle (G1, S and G2) but not M phase.
      This pattern was somewhat similar to but distinguishable from changes associated
      with an SF3B1 inhibitor, pladienolide B (PB). Both drugs led to a significant
      decrease in nascent DNA synthesis in S phase, indicative of an S phase arrest.
      However, IGG led to a much more prominent S phase arrest than PB while PB
      exhibited a more pronounced G1 arrest that decreased the proportion of cells in S
      phase as well. We also found that both drugs led to a comparable decrease in the
      proportion of cells in M phase. This work indicates that spliceosome inhibitors
      affect multiple phases of the cell cycle and that some of these effects vary in
      an agent-specific manner despite the fact that they target splicing at similar
      stages of spliceosome assembly.

PMID- 29338027
TI  - Distribution of cone density, spacing and arrangement in adult healthy retinas
      with adaptive optics flood illumination.
AB  - The aim of this article is to analyse cone density, spacing and arrangement using
      an adaptive optics flood illumination retina camera (rtx1TM) on a healthy
      population. Cone density, cone spacing and packing arrangements were measured on
      the right retinas of 109 subjects at 2 degrees , 3 degrees , 4 degrees , 5
      degrees  and 6 degrees  of eccentricity along 4 meridians. The effects of
      eccentricity, meridian, axial length, spherical equivalent, gender and age were
      evaluated. Cone density decreased on average from 28 884 +/- 3 692 cones/mm2, at
      2 degrees  of eccentricity, to 15 843 +/- 1 598 cones/mm2 at 6 degrees . A strong
      inter-individual variation, especially at 2 degrees , was observed. No important
      difference of cone density was observed between the nasal and temporal meridians
      or between the superior and inferior meridians. However, the horizontal and
      vertical meridians differed by around 14% (T-test, p<0.0001). Cone density,
      expressed in units of area, decreased as a function of axial length (r2 = 0.60),
      but remained constant (r2 = 0.05) when cone density is expressed in terms of
      visual angle supporting the hypothesis that the retina is stretched during the
      elongation of the eyeball. Gender did not modify the cone distribution. Cone
      density was slightly modified by age but only at 2 degrees . The older group
      showed a smaller density (7%). Cone spacing increased from 6,49 +/- 0,42 MUm to
      8,72 +/- 0,45 MUm respectively between 2 degrees  and 6 degrees  of eccentricity.
      The mosaic of the retina is mainly triangularly arranged (i.e. cells with 5 to 7
      neighbors) from 2 degrees  to 6 degrees . Around half of the cells had 6
      neighbors.

PMID- 29338028
TI  - Does providing more services increase the primary hospitals' revenue? An
      assessment of national essential medicine policy based on 2,675 counties in
      China.
AB  - OBJECTIVE: To understand whether the increased outpatient service provision (OSP)
      brings in enough additional income (excluding income from essential medicine) for
      primary hospitals (INCOME) to compensate for reduced costs of medicine. METHODS:
      The two outcomes, annual OSP and INCOME for the period of 2008-2012, were
      collected from 34,506 primary hospitals in 2,675 counties in 31 provinces in
      China by the national surveillance system. The data had a four-level hierarchical
      structure; time points were nested within primary hospital, hospitals within
      county, and counties within province. We fitted bivariate five-level random
      effects regression models to examine correlations between OSP and INCOME in terms
      of their mean values and dose-response effects of the essential medicine policy
      (EMP). We adjusted for the effects of time period and selected hospital
      resources. FINDINGS: The estimated correlation coefficients between the two
      outcomes' mean values were strongly positive among provinces (r = 0.910),
      moderately positive among counties (r = 0.380), and none among hospitals (r =
      0.002) and time (r = 0.007). The correlation between their policy effects was
      weakly positive among provinces (r = 0.234), but none at the county and hospital
      levels. However, there were markedly negative correlation coefficients between
      the mean and policy effects at -0.328 for OSP and -0.541 for INCOME at the
      hospital level. CONCLUSION: There was no evidence to suggest an association
      between the two outcomes in terms of their mean values and dose-response effects
      of EMP at the hospital level. This indicated that increased OSP did not bring
      enough additional INCOME. Sustainable mechanisms to compensate primary hospitals
      are needed.

PMID- 29338029
TI  - Implicit learning deficit in children with Duchenne muscular dystrophy: Evidence
      for a cerebellar cognitive impairment?
AB  - This study aimed at comparing implicit sequence learning in individuals affected
      by Duchenne Muscular Dystrophy without intellectual disability and age-matched
      typically developing children. A modified version of the Serial Reaction Time
      task was administered to 32 Duchenne children and 37 controls of comparable
      chronological age. The Duchenne group showed a reduced rate of implicit learning
      even if in the absence of global intellectual disability. This finding provides
      further evidence of the involvement of specific aspects of cognitive function in
      Duchenne muscular dystrophy and on its possible neurobiological substrate.

PMID- 29338030
TI  - Incidence, microbiology, and outcomes of endophthalmitis after 111,876 pars plana
      vitrectomies at a single, tertiary eye care hospital.
AB  - PURPOSE: To describe the incidence, risk factors, clinical presentation,
      causative organisms, and outcomes in patients with endophthalmitis following pars
      plana vitrectomy (20G and minimally invasive vitrectomy surgery (MIVS). METHODS:
      Of 111,876 vitrectomies (70,585 20-G 41,291 MIVS) performed, 45 cases developed
      acute-onset, postoperative endophthalmitis. RESULTS: The rate of culture positive
      and culture negative endophthalmitis was 0.021% (2.1/10,000 surgeries) and 0.019%
      (1.9/10,000 surgeries) overall, 0.031% (3.1/10,000 surgeries) and 0.025%
      (2.5/10,000 surgeries) in 20G, and 0.005% (0.5/10,000 surgeries) and 0.007%
      (0.7/10,000 surgeries) in the MIVS group respectively. Potential predisposing
      factors were as follows: diabetes, 46.7%; vitrectomy for vascular retinopathies,
      44.4%; and vitrectomy combined with anterior segment surgeries, 35.5%. The
      culture proven rates were 53.3% overall, 55.0% for 20G and 40.0% for MIVS. The
      most common organism was Pseudomonas aeruginosa for 20G. Klebsiella and
      Staphylococcus aureus were isolated in the two culture positive cases in MIVS
      group. The follow-up period for the patients with endophthalmitis was 586.14 +/-
      825.15 days. Seven were lost to follow up beyond one week. Of the remaining 38,
      13 (34.2%) cases had a favorable visual outcome (i.e., best-corrected visual
      acuity [BCVA] > 5/200) and 24 (63.2%) had unfavorable visual outcome (BCVA <
      5/200). Group with culture test results negative had significantly better
      outcomes (P < 0.05) as compared to those with positive. CONCLUSIONS: MIVS does
      not increase the risk of endophthalmitis. Outcomes are poor despite appropriate
      treatment, particularly in cases with culture results positive.

PMID- 29338031
TI  - Pre-existing malignancy results in increased prevalence of distinct populations
      of CD4+ T cells during sepsis.
AB  - The presence of pre-existing malignancy in murine hosts results in increased
      immune dysregulation and risk of mortality following a septic insult. Based on
      the known systemic immunologic changes that occur in cancer hosts, we
      hypothesized that the presence of pre-existing malignancy would result in
      phenotypic and functional changes in CD4+ T cell responses following sepsis. In
      order to conduct a non-biased, unsupervised analysis of phenotypic differences
      between CD4+ T cell compartments, cohorts of mice were injected with LLC1 tumor
      cells and tumors were allowed to grow for 3 weeks. These cancer hosts and age
      matched non-cancer controls were then subjected to CLP. Splenocytes were
      harvested at 24h post CLP and flow cytometry and SPADE (Spanning-tree Progression
      Analysis of Density-normalized Events) were used to analyze populations of CD4+
      cells most different between the two groups. Results indicated that relative to
      non-cancer controls, cancer mice contained more resting memory CD4+ T cells, more
      activated CD4+ effectors, and fewer naive CD4+ T cells during sepsis, suggesting
      that the CD4+ T cell compartment in cancer septic hosts is one of increased
      activation and differentiation. Moreover, cancer septic animals exhibited
      expansion of two distinct subsets of CD4+ T cells relative to previously healthy
      septic controls. Specifically, we identified increases in both a PD-1hi
      population and a distinct 2B4hi BTLAhi LAG-3hi population in cancer septic
      animals. By combining phenotypic analysis of exhaustion markers with functional
      analysis of cytokine production, we found that PD-1+ CD4+ cells in cancer hosts
      failed to make any cytokines following CLP, while the 2B4+ PD-1lo cells in cancer
      mice secreted increased TNF during sepsis. In sum, the immunophenotypic landscape
      of cancer septic animals is characterized by both increased CD4+ T cell
      activation and exhaustion, findings that may underlie the observed increased
      mortality in mice with pre-existing malignancy following sepsis.

PMID- 29338032
TI  - Perceptions of healthcare quality in Ghana: Does health insurance status matter?
AB  - This study's objective is to provide an alternative explanation for the low
      enrolment in health insurance in Ghana by analysing differences in perceptions
      between the insured and uninsured of the non-technical quality of healthcare. It
      further explores the association between insurance status and perception of
      healthcare quality to ascertain whether insurance status matters in the
      perception of healthcare quality. Data from a survey of 1,903 households living
      in the catchment area of 64 health centres were used for the analysis. Two sample
      independent t-tests were employed to compare the average perceptions of the
      insured and uninsured on seven indicators of non-technical quality of healthcare.
      A generalised ordered logit regression, controlling for socio-economic
      characteristics and clustering at the health facility level, tested the
      association between insurance status and perceived quality of healthcare. The
      perceptions of the insured were found to be significantly more negative than the
      uninsured and those of the previously insured were significantly more negative
      than the never insured. Being insured was associated with a significantly lower
      perception of healthcare quality. Thus, once people are insured, they tend to
      perceive the quality of healthcare they receive as poor compared to those without
      insurance. This study demonstrated that health insurance status matters in the
      perceptions of healthcare quality. The findings also imply that perceptions of
      healthcare quality may be shaped by individual experiences at the health
      facilities, where the insured and uninsured may be treated differently. Health
      insurance then becomes less attractive due to the poor perception of the
      healthcare quality provided to individuals with insurance, resulting in low
      demand for health insurance in Ghana. Policy makers in Ghana should consider
      redesigning, reorganizing, and reengineering the National Healthcare Insurance
      Scheme to ensure the provision of better quality healthcare for both the insured
      and uninsured.

PMID- 29338035
TI  - Genome wide identification of wheat and Brachypodium type one protein
      phosphatases and functional characterization of durum wheat TdPP1a.
AB  - Reversible phosphorylation is an essential mechanism regulating signal
      transduction during development and environmental stress responses. An important
      number of dephosphorylation events in the cell are catalyzed by type one protein
      phosphatases (PP1), which catalytic activity is driven by the binding of
      regulatory proteins that control their substrate specificity or subcellular
      localization. Plants harbor several PP1 isoforms accounting for large functional
      redundancies. While animal PP1s were reported to play relevant roles in
      controlling multiple cellular processes, plant orthologs remain poorly studied.
      To decipher the role of plant PP1s, we compared PP1 genes from three monocot
      species, Brachypodium, common wheat and rice at the genomic and transcriptomic
      levels. To gain more insight into the wheat PP1 proteins, we identified and
      characterized TdPP1a, the first wheat type one protein phosphatase from a
      Tunisian durum wheat variety Oum Rabiaa3. TdPP1a is highly conserved in sequence
      and structure when compared to mammalian, yeast and other plant PP1s. We
      demonstrate that TdPP1a is an active, metallo-dependent phosphatase in vitro and
      is able to interact with AtI2, a typical regulator of PP1 functions. Also, TdPP1a
      is capable to complement the heat stress sensitivity of the yeast mutant
      indicating that TdPP1a is functional also in vivo. Moreover, transient expression
      of TdPP1a::GFP in tobacco leaves revealed that it is ubiquitously distributed
      within the cell, with a strong accumulation in the nucleus. Finally,
      transcriptional analyses showed similar expression levels in roots and leaves of
      durum wheat seedlings. Interestingly, the expression in leaves is significantly
      induced following salinity stress, suggesting a potential role of TdPP1a in wheat
      salt stress response.

PMID- 29338034
TI  - Clonal growth strategy, diversity and structure: A spatiotemporal response to
      sedimentation in tropical Cyperus papyrus swamps.
AB  - Land degradation and soil erosion in the upper catchments of tropical lakes
      fringed by papyrus vegetation can result in a sediment load gradient from land to
      lakeward. Understanding the dynamics of clonal modules (ramets and genets) and
      growth strategies of plants on such a gradient in both space and time is critical
      for exploring a species adaptation and processes regulating population structure
      and differentiation. We assessed the spatial and temporal dynamics in clonal
      growth, diversity, and structure of an emergent macrophyte, Cyperus papyrus
      (papyrus), in response to two contrasting sedimentation regimes by combining
      morphological traits and genotype data using 20 microsatellite markers. A total
      of 636 ramets from six permanent plots (18 x 30 m) in three Ethiopian papyrus
      swamps, each with discrete sedimentation regimes (high vs. low) were sampled for
      two years. We found that ramets under the high sedimentation regime (HSR) were
      significantly clumped and denser than the sparse and spreading ramets under the
      low sedimentation regime (LSR). The HSR resulted in significantly different
      ramets with short culm height and girth diameter as compared to the LSR. These
      results indicated that C. papyrus ameliorates the effect of sedimentation by
      shifting clonal growth strategy from guerrilla (in LSR) to phalanx (in HSR).
      Clonal richness, size, dominance, and clonal subrange differed significantly
      between sediment regimes and studied time periods. Each swamp under HSR revealed
      a significantly high clonal richness (R = 0.80) as compared to the LSR (R =
      0.48). Such discrepancy in clonal richness reflected the occurrence of initial
      and repeated seedling recruitment strategies as a response to different
      sedimentation regimes. Overall, our spatial and short-term temporal observations
      highlighted that HSR enhances clonal richness and decreases clonal subrange owing
      to repeated seedling recruitment and genets turnover.

PMID- 29338033
TI  - Intermittent, low dose carbon monoxide exposure enhances survival and
      dopaminergic differentiation of human neural stem cells.
AB  - Exploratory studies using human fetal tissue have suggested that intrastriatal
      transplantation of dopaminergic neurons may become a future treatment for
      patients with Parkinson's disease. However, the use of human fetal tissue is
      compromised by ethical, regulatory and practical concerns. Human stem cells
      constitute an alternative source of cells for transplantation in Parkinson's
      disease, but efficient protocols for controlled dopaminergic differentiation need
      to be developed. Short-term, low-level carbon monoxide (CO) exposure has been
      shown to affect signaling in several tissues, resulting in both protection and
      generation of reactive oxygen species. The present study investigated the effect
      of CO produced by a novel CO-releasing molecule on dopaminergic differentiation
      of human neural stem cells. Short-term exposure to 25 ppm CO at days 0 and 4
      significantly increased the relative content of beta-tubulin III-immunoreactive
      immature neurons and tyrosine hydroxylase expressing catecholaminergic neurons,
      as assessed 6 days after differentiation. Also the number of microtubule
      associated protein 2-positive mature neurons had increased significantly.
      Moreover, the content of apoptotic cells (Caspase3) was reduced, whereas the
      expression of a cell proliferation marker (Ki67) was left unchanged. Increased
      expression of hypoxia inducible factor-1alpha and production of reactive oxygen
      species (ROS) in cultures exposed to CO may suggest a mechanism involving
      mitochondrial alterations and generation of ROS. In conclusion, the present
      procedure using controlled, short-term CO exposure allows efficient dopaminergic
      differentiation of human neural stem cells at low cost and may as such be useful
      for derivation of cells for experimental studies and future development of donor
      cells for transplantation in Parkinson's disease.

PMID- 29338036
TI  - Static magnetic field enhances the anticancer efficacy of capsaicin on HepG2
      cells via capsaicin receptor TRPV1.
AB  - Static magnetic field (SMF) has shown some possibilities for cancer therapies. In
      particular, the combinational effect between SMF and anti-cancer drugs has drawn
      scientists' attentions in recent years. However, the underlying mechanism for the
      drug-specific synergistic effect is far from being understood. Besides, the drugs
      used are all conventional chemotherapy drugs, which may cause unpleasant side
      effects. In this study, our results demonstrate for the first time that SMF could
      enhance the anti-cancer effect of natural compound, capsaicin, on HepG2 cancer
      cells through the mitochondria-dependent apoptosis pathway. We found that the
      synergistic effect could be due to that SMF increased the binding efficiency of
      capsaicin for the TRPV1 channel. These findings may provide a support to develop
      an application of SMF for cancer therapy. The present study offers the first
      trial in combining SMF with natural compound on anti-cancer treatment, which
      provides additional insight into the interaction between SMF and anti-cancer
      drugs and opens the door for the development of new strategies in fighting cancer
      with minimum cytotoxicity and side effects.

PMID- 29338037
TI  - Stentless vs. stented bioprosthesis for aortic valve replacement: A case matched
      comparison of long-term follow-up and subgroup analysis of patients with native
      valve endocarditis.
AB  - BACKGROUND: Current retrospective evidence suggests similar clinical and superior
      hemodynamic outcomes of the Sorin Freedom Solo stentless aortic valve (SFS)
      (LivaNova PLC, London, UK) compared to the Carpentier Edwards Perimount stented
      aortic valve (CEP) (Edwards Lifesciences Inc., Irvine, California, USA). To date,
      no reports exist describing case-matched long-term outcomes and analysis for
      treatment of native valve endocarditis (NVE). METHODS: From 2004 through 2014, 77
      consecutive patients (study group, 59.7% male, 68.9 +/- 12.5 years, logEuroSCORE
      II 7.6 +/- 12.3%) received surgical aortic valve replacement (SAVR) with the SFS.
      A control group of patients after SAVR with the CEP was retrieved from our
      database and matched to the study group regarding 15 parameters including
      preoperative endocarditis. Acute perioperative outcomes and follow-up data (mean
      follow-up time 48.7+/-29.8 months, 95% complete) were retrospectively analyzed.
      RESULTS: No differences in early mortality occurred during 30-day follow up
      (3/77; 3.9% vs. 4/77; 5.2%; p = 0.699). Echocardiographic findings revealed lower
      postprocedural transvalvular pressure gradients (max. 17.0 +/- 8.2 vs. 24.5 +/-
      9.2 mmHg, p< 0.001/ mean pressure of 8.4 +/- 4.1 vs. 13.1 +/- 5.9 mmHg, p< 0.001)
      in the SFS group. Structural valve degeneration (SVD) (5.2% vs. 0%; p = 0.04) and
      valve explantation due to SVD or prosthetic valve endocarditis (PVE) (9.1% vs.
      1.3%; p = 0.04) was more frequent in the SFS group. All-cause mortality during
      follow-up was 20.8% vs. 14.3% (p = 0.397). When patients were divided into
      subgroups of NVE and respective utilized bioprosthesis, the SFS presented
      impaired outcomes regarding mortality in NVE cases (p = 0.031). CONCLUSIONS: The
      hemodynamic superiority of the SFS was confirmed in this comparison. However,
      clinical outcomes in terms of SVD and PVE rates, as well as survival after NVE,
      were inferior in this study. Therefore, we are reluctant to recommend utilization
      of the SFS for treatment of NVE.

PMID- 29338038
TI  - Does the leading pharmaceutical reform in China really solve the issue of overly
      expensive healthcare services? Evidence from an empirical study.
AB  - BACKGROUND: Healthcare system reform of Sanming city has become a leading
      healthcare reform model in China. It has developed a rigorous pharmaceutical
      reform consisted of the Zero Mark-up Drug Policy and the Centralized Procurement
      of Medicine Policy to bring down drug expenses and total health expenditures.
      However, despite the credit and much attention have been given to Sanming's
      pharmaceutical reform, its impact still remains unclear. Therefore, the purpose
      of this study was to explore the impact of the pharmaceutical reform of Sanming
      on both drug and total health expenditures. METHODS: Interrupted time series
      analysis with three segments divided by two intervention points was employed to
      evaluate the impact of the pharmaceutical reform. Segment 1 was the pre-reform
      period which captured the baseline information. Segment 2 occurred after the
      first intervention point when the Zero Mark-up Drug Policy was implemented,
      whereas Segment 3 was after the implementation of the Centralized Procurement of
      Medicine Policy. Primary outcomes are outpatient drug expenditure, outpatient
      total health expenditure, inpatient drug expenditure, and inpatient total health
      expenditure. Data spanning from May 2012 to May 2014 are included. RESULTS: Both
      drug and total health expenditures exhibited rising trends before any policy was
      carried out. The launch of Zero Mark-up Drug Policy led to significant instant
      reductions in levels of outpatient drug expenditure (coefficient = -6,602.99,
      p<0.01), outpatient total health expenditure (coefficient = -9,958.58, p<0.05),
      inpatient drug expenditure (coefficient = -7,520.90, p<0.01), and inpatient total
      health expenditure (coefficient = -16,737, p<0.01). Moreover, the previous upward
      trends were changed into downward trends for inpatient drug expenditure
      (coefficient = -2,747.02, p = 0.00) and total health expenditure (coefficient = 
      3,069.29, p = 0.12). However, after the implementation of Centralized Procurement
      of Medicine Policy, we observed no significant instant level changes and also,
      the inpatient drug expenditure (coefficient = 372.95, p = 0.01) and total health
      expenditure (coefficient = 788.76, p = 0.06) resumed upward trends again.
      CONCLUSIONS: Although the pharmaceutical reform could control or reduced drug
      expenditure and total health expenditure in short term, expenditures gradually
      resumed growing again and reached or even exceeded their baseline levels of pre
      reform period, indicating the effect became weakened or even faded out in long
      term. In all, the pharmaceutical reform as a whole failed to meet its goal of
      combating sharp growth of drug and total health expenditure.

PMID- 29338039
TI  - STAT3 expression by myeloid cells is detrimental for the T- cell-mediated control
      of infection with Mycobacterium tuberculosis.
AB  - STAT3 is a master regulator of the immune responses. Here we show that M.
      tuberculosis-infected stat3fl/fl lysm cre mice, defective for STAT3 in myeloid
      cells, contained lower bacterial load in lungs and spleens, reduced granuloma
      extension but higher levels of pulmonary neutrophils. STAT3-deficient macrophages
      showed no improved control of intracellular mycobacterial growth. Instead,
      protection associated to elevated ability of stat3fl/fl lysm cre antigen
      presenting cells (APCs) to release IL-6 and IL-23 and to stimulate IL-17
      secretion by mycobacteria-specific T cells. The increased IL-17 secretion
      accounted for the improved control of infection since neutralization of IL-17
      receptor A in stat3fl/fl lysm cre mice hampered bacterial control. APCs lacking
      SOCS3, which inhibits STAT3 activation via several cytokine receptors, were poor
      inducers of priming and of the IL-17 production by mycobacteria-specific T cells.
      In agreement, socs3fl/fl cd11c cre mice deficient of SOCS3 in DCs showed
      increased susceptibility to M. tuberculosis infection. While STAT3 in APCs
      hampered IL-17 responses, STAT3 in mycobacteria-specific T cells was critical for
      IL-17 secretion, while SOCS3 in T cells impeded IL-17 secretion. Altogether,
      STAT3 signalling in myeloid cells is deleterious in the control of infection with
      M. tuberculosis.

PMID- 29338040
TI  - Identification and expression analyses of WRKY genes reveal their involvement in
      growth and abiotic stress response in watermelon (Citrullus lanatus).
AB  - Despite identification of WRKY family genes in numerous plant species, a little
      is known about WRKY genes in watermelon, one of the most economically important
      fruit crops around the world. Here, we identified a total of 63 putative WRKY
      genes in watermelon and classified them into three major groups (I-III) and five
      subgroups (IIa-IIe) in group II. The structure analysis indicated that ClWRKYs
      with different WRKY domains or motifs may play different roles by regulating
      respective target genes. The expressions of ClWRKYs in different tissues indicate
      that they are involved in various tissue growth and development. Furthermore, the
      diverse responses of ClWRKYs to drought, salt, or cold stress suggest that they
      positively or negatively affect plant tolerance to various abiotic stresses. In
      addition, the altered expression patterns of ClWRKYs in response to phytohormones
      such as, ABA, SA, MeJA, and ETH, imply the occurrence of complex cross-talks
      between ClWRKYs and plant hormone signals in regulating plant physiological and
      biological processes. Taken together, our findings provide valuable clues to
      further explore the function and regulatory mechanisms of ClWRKY genes in
      watermelon growth, development, and adaption to environmental stresses.

PMID- 29338041
TI  - Cadherins in the retinal pigment epithelium (RPE) revisited: P-cadherin is the
      highly dominant cadherin expressed in human and mouse RPE in vivo.
AB  - The retinal pigment epithelium (RPE) supports the health and function of retinal
      photoreceptors and is essential for normal vision. RPE cells are post-mitotic,
      terminally differentiated, and polarized epithelial cells. In pathological
      conditions, however, they lose their epithelial integrity, become dysfunctional,
      even dedifferentiate, and ultimately die. The integrity of epithelial cells is
      maintained, in part, by adherens junctions, which are composed of cadherin
      homodimers and p120-, beta-, and alpha-catenins linking to actin filaments. While
      E-cadherin is the major cadherin for forming the epithelial phenotype in most
      epithelial cell types, it has been reported that cadherin expression in RPE cells
      is different from other epithelial cells based on results with cultured RPE
      cells. In this study, we revisited the expression of cadherins in the RPE to
      clarify their relative contribution by measuring the absolute quantity of cDNAs
      produced from mRNAs of three classical cadherins (E-, N-, and P-cadherins) in the
      RPE in vivo. We found that P-cadherin (CDH3) is highly dominant in both mouse and
      human RPE in situ. The degree of dominance of P-cadherin is surprisingly large,
      with mouse Cdh3 and human CDH3 accounting for 82-85% and 92-93% of the total of
      the three cadherin mRNAs, respectively. We confirmed the expression of P-cadherin
      protein at the cell-cell border of mouse RPE in situ by immunofluorescence.
      Furthermore, we found that oxidative stress induces dissociation of P-cadherin
      and beta-catenin from the cell membrane and subsequent translocation of beta
      catenin into the nucleus, resulting in activation of the canonical Wnt/beta
      catenin pathway. This is the first report of absolute comparison of the
      expression of three cadherins in the RPE, and the results suggest that the
      physiological role of P-cadherin in the RPE needs to be reevaluated.

PMID- 29338042
TI  - A pharmacological screen for compounds that rescue the developmental lethality of
      a Drosophila ATM mutant.
AB  - Ataxia-telangiectasia (A-T) is a neurodegenerative disease caused by mutation of
      the A-T mutated (ATM) gene. ATM encodes a protein kinase that is activated by DNA
      damage and phosphorylates many proteins, including those involved in DNA repair,
      cell cycle control, and apoptosis. Characteristic biological and molecular
      functions of ATM observed in mammals are conserved in Drosophila melanogaster. As
      an example, conditional loss-of-function ATM alleles in flies cause progressive
      neurodegeneration through activation of the innate immune response. However,
      unlike in mammals, null alleles of ATM in flies cause lethality during
      development. With the goals of understanding biological and molecular roles of
      ATM in a whole animal and identifying candidate therapeutics for A-T, we
      performed a screen of 2400 compounds, including FDA-approved drugs, natural
      products, and bioactive compounds, for modifiers of the developmental lethality
      caused by a temperature-sensitive ATM allele (ATM8) that has reduced kinase
      activity at non-permissive temperatures. Ten compounds reproducibly suppressed
      the developmental lethality of ATM8 flies, including Ronnel, which is an
      organophosphate. Ronnel and other suppressor compounds are known to cause
      mitochondrial dysfunction or to inhibit the enzyme acetylcholinesterase, which
      controls the levels of the neurotransmitter acetylcholine, suggesting that
      detrimental consequences of reduced ATM kinase activity can be rescued by
      inhibiting the function of mitochondria or increasing acetylcholine levels. We
      carried out further studies of Ronnel because, unlike the other compounds that
      suppressed the developmental lethality of homozygous ATM8 flies, Ronnel was toxic
      to the development of heterozygous ATM8 flies. Ronnel did not affect the innate
      immune response of ATM8 flies, and it further increased the already high levels
      of DNA damage in brains of ATM8 flies, but its effects were not harmful to the
      lifespan of rescued ATM8 flies. These results provide new leads for understanding
      the biological and molecular roles of ATM and for the treatment of A-T.

PMID- 29338043
TI  - Search for independent (beta/alpha)4 subdomains in a (beta/alpha)8 barrel beta
      glucosidase.
AB  - Proteins that fold as (beta/alpha)8 barrels are thought to have evolved from half
      barrels that underwent duplication and fusion events. The evidence is
      particularly clear for small barrels, which have almost identical halves.
      Additionally, computational calculations of the thermodynamic stability of these
      structures in the presence of denaturants have revealed that (beta/alpha)8
      barrels contain two subunits or domains corresponding to half-barrels. Hence,
      within (beta/alpha)8 barrels, half-barrels are self-contained units. Here, we
      tested this hypothesis using beta-glucosidase from the bacterium Thermotoga
      maritima (bglTm), which has a (beta/alpha)8 barrel structure. Mutations were
      introduced to disrupt the noncovalent contacts between its halves and reveal the
      presence of two domains within bglTm, thus resulting in the creation of mutants
      T1 (containing W12A and I217A mutations) and T2 (containing W12A, H195A, I217A
      and F404A mutations). Mutants T1 and T2 were properly folded, as indicated by
      their fluorescence spectra and enzyme kinetic parameters. T1 and wild-type bglTm
      were equally stable, as shown by the results of thermal inactivation,
      differential scanning fluorimetry and guanidine hydrochloride denaturation
      experiments. However, T2 showed a first-order inactivation at 80 degrees C, a
      single melting temperature of 82 degrees C and only one transition concentration
      (c50) in 2.4 M guanidine hydrochloride. Additionally, T1 and T2 exhibited a
      cooperative denaturation process that followed a two-state model (m-values equal
      to 1.4 and 1.6 kcal/mol/M, respectively), similar to that of wild-type bglTm (1.2
      kcal/mol/M). Hence, T1 and T2 each denatured as a single unit, although they
      contained different degrees of disruption between their halves. In conclusion,
      bglTm halves are equivalent in terms of their thermal and chemical stability;
      thus, their separate contributions to (beta/alpha)8 barrel unfolding cannot be
      disentangled.

PMID- 29338046
TI  - Correction: Women's health in the occupied Palestinian territories: Contextual
      influences on subjective and objective health measures.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0186610.].

PMID- 29338044
TI  - Probing the changes in gene expression due to alpha-crystallin mutations in mouse
      models of hereditary human cataract.
AB  - The mammalian eye lens expresses a high concentration of crystallins (alpha, beta
      and gamma-crystallins) to maintain the refractive index essential for lens
      transparency. Crystallins are long-lived proteins that do not turnover throughout
      life. The structural destabilization of crystallins by UV exposure, glycation,
      oxidative stress and mutations in crystallin genes leads to protein aggregation
      and development of cataracts. Several destabilizing mutations in crystallin genes
      are linked with human autosomal dominant hereditary cataracts. To investigate the
      mechanism by which the alpha-crystallin mutations Cryaa-R49C and Cryab-R120G lead
      to cataract formation, we determined whether these mutations cause an altered
      expression of specific transcripts in the lens at an early postnatal age by RNA
      seq analysis. Using knock-in mouse models previously generated in our laboratory,
      in the present work, we identified genes that exhibited altered abundance in the
      mutant lenses, including decreased transcripts for Clic5, an intracellular water
      channel in Cryaa-R49C heterozygous mutant lenses, and increased transcripts for
      Eno1b in Cryab-R120G heterozygous mutant lenses. In addition, RNA-seq analysis
      revealed increased histones H2B, H2A, and H4 gene expression in Cryaa-R49C mutant
      lenses, suggesting that the alphaA-crystallin mutation regulates histone
      expression via a transcriptional mechanism. Additionally, these studies confirmed
      the increased expression of histones H2B, H2A, and H4 by proteomic analysis of
      Cryaa-R49C knock-in and Cryaa;Cryab gene knockout lenses reported previously.
      Taken together, these findings offer additional insight into the early
      transcriptional changes caused by Cryaa and Cryab mutations associated with
      autosomal dominant human cataracts, and indicate that the transcript levels of
      certain genes are affected by the expression of mutant alpha-crystallin in vivo.

PMID- 29338045
TI  - Protection induced by virus-like particle vaccine containing tandem repeat gene
      of respiratory syncytial virus G protein.
AB  - Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract
      illness in infants, young children and the elderly. However, there is no licensed
      vaccine available against RSV infection. In this study, we generated virus-like
      particle (VLP) vaccine and investigated the vaccine efficacy in a mouse model.
      For VLP vaccines, tandem gene (1-780 bp) for V1 VLPs and tandem repeat gene
      (repeated 450-780 bp) for V5 VLPs were constructed in pFastBacTM vectors,
      respectively. Influenza matrix protein 1 (M1) was used as a core protein in the
      VLPs. Notably, upon challenge infection, significantly lower virus loads were
      measured in the lung of mice immunized with V1 or V5 VLPs compared to those of
      naive mice and formalin-inactivated RSV immunized control mice. In particular, V5
      VLPs immunization showed significantly lower virus titers than V1 VLPs
      immunization. Furthermore, V5 VLPs immunization elicited increased memory B cells
      responses in the spleen. These results indicated that V5 VLP vaccine containing
      tandem repeat gene protein provided better protection than V1 VLPs with
      significantly decreased inflammation in the lungs. Thus, V5 VLPs could be a
      potential vaccine candidate against RSV.

PMID- 29338047
TI  - Amino acid substitutions affecting aspartic acid 605 and valine 606 decrease the
      interaction strength between the influenza virus RNA polymerase PB2 '627' domain
      and the viral nucleoprotein.
AB  - The influenza virus RNA genome is transcribed and replicated in the context of
      the viral ribonucleoprotein (vRNP) complex by the viral RNA polymerase. The
      nucleoprotein (NP) is the structural component of the vRNP providing a scaffold
      for the viral RNA. In the vRNP as well as during transcription and replication
      the viral polymerase interacts with NP but it is unclear which parts of the
      polymerase and NP mediate these interactions. Previously the C-terminal '627'
      domain (amino acids 538-693) of PB2 was shown to interact with NP. Here we report
      that a fragment encompassing amino acids 146-185 of NP is sufficient to mediate
      this interaction. Using NMR chemical shift perturbation assays we show that amino
      acid region 601 to 607 of the PB2 '627' domain interacts with this fragment of
      NP. Substitutions of these PB2 amino acids resulted in diminished RNP activity
      and surface plasmon resonance assays showed that amino acids D605 was essential
      for the interaction with NP and V606 may also play a partial role in the
      interaction. Collectively these results reveal a possible interaction surface
      between NP and the PB2 subunit of the RNA polymerase complex.

PMID- 29338048
TI  - Ebola virus requires a host scramblase for externalization of phosphatidylserine
      on the surface of viral particles.
AB  - Cell surface receptors for phosphatidylserine contribute to the entry of Ebola
      virus (EBOV) particles, indicating that the presence of phosphatidylserine in the
      envelope of EBOV is important for the internalization of EBOV particles.
      Phosphatidylserine is typically distributed in the inner layer of the plasma
      membrane in normal cells. Progeny virions bud from the plasma membrane of
      infected cells, suggesting that phosphatidylserine is likely flipped to the outer
      leaflet of the plasma membrane in infected cells for EBOV virions to acquire it.
      Currently, the intracellular dynamics of phosphatidylserine during EBOV infection
      are poorly understood. Here, we explored the role of XK-related protein (Xkr) 8,
      which is a scramblase responsible for exposure of phosphatidylserine in the
      plasma membrane of apoptotic cells, to understand its significance in
      phosphatidylserine-dependent entry of EBOV. We found that Xkr8 and transiently
      expressed EBOV glycoprotein GP often co-localized in intracellular vesicles and
      the plasma membrane. We also found that co-expression of GP and viral major
      matrix protein VP40 promoted incorporation of Xkr8 into ebolavirus-like particles
      (VLPs) and exposure of phosphatidylserine on their surface, although only a
      limited amount of phosphatidylserine was exposed on the surface of the cells
      expressing GP and/or VP40. Downregulating Xkr8 or blocking caspase-mediated Xkr8
      activation did not affect VLP production, but they reduced the amount of
      phosphatidylserine on the VLPs and their uptake in recipient cells. Taken
      together, our findings indicate that Xkr8 is trafficked to budding sites via GP
      containing vesicles, is incorporated into VLPs, and then promote the entry of the
      released EBOV to cells in a phosphatidylserine-dependent manner.

PMID- 29338050
TI  - Correction: Utilization of urea and expression profiles of related genes in the
      dinoflagellate Prorocentrum donghaiense.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0187837.].

PMID- 29338049
TI  - Contribution of the ankle-brachial index to improve the prediction of coronary
      risk: The ARTPER cohort.
AB  - BACKGROUND: The different cardiovascular risk prediction scales currently
      available are not sufficiently sensitive. AIM: The aim of the present study was
      to analyze the contribution of the ankle-brachial index (ABI) added to the
      Framingham and REGICOR risk scales for the reclassification of cardiovascular
      risk after a 9-year follow up of a Mediterranean population with low
      cardiovascular risk. DESIGN AND SETTING: A population-based prospective cohort
      study was performed in the province of Barcelona, Spain. METHOD: A total of 3,786
      subjects >49 years were recruited from 2006-2008. Baseline ABI was performed and
      cardiovascular risk was calculated with the Framingham and REGICOR scales. The
      participants were followed until November 2016 by telephone and review of the
      clinical history every 6 months to confirm the possible appearance of
      cardiovascular events. RESULTS: 2,716 individuals participated in the study.
      There were 126 incidental cases of first coronary events (5%) during follow up.
      The incidence of coronary events in patients with ABI <0.9 was 4-fold greater
      than that of subjects with a normal ABI (17.2/1,000 persons-year versus 4.8/1,000
      persons-year). Improvement in the predictive capacity of REGICOR scale was
      observed on including ABI in the model, obtaining a net reclassification
      improvement of 7% (95% confidence interval 0%-13%) for REGICOR+ ABI. Framingham +
      ABI obtained a NRI of 4% (-2%-11%). CONCLUSION: The results of the present study
      support the addition of the ABI as a tool to help in the reclassification of
      cardiovascular risk and to confirm the greater incidence of coronary events in
      patients with ABI < 0.9.

PMID- 29338051
TI  - Correction: Cordycepin promotes apoptosis in renal carcinoma cells by activating
      the MKK7-JNK signaling pathway through inhibition of c-FLIPL expression.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0186489.].

PMID- 29338052
TI  - Correction: Diversification dynamics, species sorting, and changes in the
      functional diversity of marine benthic gastropods during the Pliocene-Quaternary
      at temperate western South America.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0187140.].

PMID- 29338053
TI  - Selenium regulation of selenoprotein enzyme activity and transcripts in a pilot
      study with Founder strains from the Collaborative Cross.
AB  - Rodents and humans have 24-25 selenoproteins, and these proteins contain the 21st
      amino acid, selenocysteine, incorporated co-translationally into the peptide
      backbone in a series of reactions dependent on at least 6 unique gene products.
      In selenium (Se) deficiency, there is differential regulation of selenoprotein
      expression, whereby levels of some selenoproteins and their transcripts decrease
      dramatically in Se deficiency, but other selenoprotein transcripts are spared
      this decrease; the underlying mechanism, however, is not fully understood. To
      begin explore the genetic basis for this variation in regulation by Se status in
      a pilot study, we fed Se-deficient or Se-adequate diets (0.005 or 0.2 MUg Se/g,
      respectively) for eight weeks to the eight Founder strains of the Collaborative
      Cross. We found rather uniform expression of selenoenzyme activity for
      glutathione peroxidase (Gpx) 3 in plasma, Gpx1 in red blood cells, and Gpx1,
      Gpx4, and thioredoxin reductase in liver. In Founder mice, Se deficiency
      decreased each of these activities to a similar extent. Regulation of
      selenoprotein transcript expression by Se status was also globally retained
      intact, with dramatic down-regulation of Gpx1, Selenow, and Selenoh transcripts
      in all 8 strains of Founder mice. These results indicate that differential
      regulation of selenoprotein expression by Se status is an essential aspect of Se
      metabolism and selenoprotein function. A few lone differences in Se regulation
      were observed for individual selenoproteins in this pilot study, but these
      differences did not single-out one strain or one selenoprotein that consistently
      had unique Se regulation of selenoprotein expression. These differences should be
      affirmed in larger studies; use of the Diversity Outbred and Collaborative Cross
      strains may help to better define the functions of these selenoproteins.

PMID- 29338054
TI  - Correction: Selective serotonin reuptake inhibitors and venlafaxine in pregnancy:
      Changes in drug disposition.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0181082.].

PMID- 29338056
TI  - Context-dependent autoprocessing of human immunodeficiency virus type 1 protease
      precursors.
AB  - HIV-1 protease autoprocessing is responsible for liberation of free mature
      protease (PR) from the Gag-Pol polyprotein precursor. A cell-based model system
      was previously developed to examine the autoprocessing mechanism of fusion
      precursors carrying the p6*-PR miniprecursor sandwiched between various proteins
      or epitopes. We here report that precursor autoprocessing is context-dependent as
      its activity and outcomes can be modulated by sequences upstream of p6*-PR. This
      was exemplified by the 26aa maltose binding protein (MBP) signal peptide (SigP)
      when placed at the N-terminus of a fusion precursor. The mature PRs released from
      SigP-carrying precursors are resistant to self-degradation whereas those released
      from SigP-lacking fusion precursors are prone to self-degradation. A H69D
      mutation in PR abolished autoprocessing of SigP-containing fusion precursors
      whereas it only partially suppressed autoprocessing of fusion precursors lacking
      SigP. An autoprocessing deficient GFP fusion precursor with SigP exhibited a
      subcellular distribution pattern distinct from the one without it in transfected
      HeLa cells. Furthermore, a SigP fusion precursor carrying a substitution at the
      P1 position released the mature PR and PR-containing fragments that were
      different from those released from the precursor carrying the same mutation but
      lacking SigP. We also examined autoprocessing outcomes in viral particles
      produced by a NL4-3 derived proviral construct and demonstrated the existence of
      several PR-containing fragments along with the mature PR. Some of these resembled
      the SigP precursor autoprocessing outcomes. This finding of context-dependent
      modulation reveals the complexity of precursor autoprocessing regulation that
      most likely accompanies sequence variation imposed by the evolution of the
      upstream Gag moiety.

PMID- 29338055
TI  - A novel Gerstmann-Straussler-Scheinker disease mutation defines a precursor for
      amyloidogenic 8 kDa PrP fragments and reveals N-terminal structural changes
      shared by other GSS alleles.
AB  - To explore pathogenesis in a young Gerstmann-Straussler-Scheinker Disease (GSS)
      patient, the corresponding mutation, an eight-residue duplication in the
      hydrophobic region (HR), was inserted into the wild type mouse PrP gene.
      Transgenic (Tg) mouse lines expressing this mutation (Tg.HRdup) developed
      spontaneous neurologic syndromes and brain extracts hastened disease in low
      expressor Tg.HRdup mice, suggesting de novo formation of prions. While Tg.HRdup
      mice exhibited spongiform change, PrP aggregates and the anticipated GSS hallmark
      of a proteinase K (PK)-resistant 8 kDa fragment deriving from the center of PrP,
      the LGGLGGYV insertion also imparted alterations in PrP's unstructured N
      terminus, resulting in a 16 kDa species following thermolysin exposure. This
      species comprises a plausible precursor to the 8 kDa PK-resistant fragment and
      its detection in adolescent Tg.HRdup mice suggests that an early start to
      accumulation could account for early disease of the index case. A 16 kDa
      thermolysin-resistant signature was also found in GSS patients with P102L, A117V,
      H187R and F198S alleles and has coordinates similar to GSS stop codon mutations.
      Our data suggest a novel shared pathway of GSS pathogenesis that is fundamentally
      distinct from that producing structural alterations in the C-terminus of PrP, as
      observed in other prion diseases such as Creutzfeldt-Jakob Disease and scrapie.

PMID- 29338057
TI  - RNA-sequencing analysis of fungi-induced transcripts from the bamboo wireworm
      Melanotus cribricollis (Coleoptera: Elateridae) larvae.
AB  - Larvae of Melanotus cribricollis, feed on bamboo shoots and roots, causing
      serious damage to bamboo in Southern China. However, there is currently no
      effective control measure to limit the population of this underground pest.
      Previously, a new entomopathogenic fungal strain isolated from M. cribricollis
      larvae cadavers named Metarhizium pingshaense WP08 showed high pathogenic
      efficacy indoors, indicated that the fungus could be used as a bio-control
      measure. So far, the genetic backgrounds of both M. cribricollis and M.
      pingshaense WP08 were blank. Here, we analyzed the whole transcriptome of M.
      cribricollis larvae, infected with M. pingshaense WP08 or not, using high
      throughput next generation sequencing technology. In addition, the transcriptome
      sequencing of M. pingshaense WP08 was also performed for data separation of those
      two non-model species. The reliability of the RNA-Seq data was also validated
      through qRT-PCR experiment. The de novo assembly, functional annotation, sequence
      comparison of four insect species, and analysis of DEGs, enriched pathways, GO
      terms and immune related candidate genes were operated. The results indicated
      that, multiple defense mechanisms of M. cribricollis larvae are initiated to
      protect against the more serious negative effects caused by fungal infection. To
      our knowledge, this was the first report of transcriptome analysis of Melanotus
      spp. infected with a fungus, and it could provide insights to further explore
      insect-fungi interaction mechanisms.

PMID- 29338058
TI  - Menstrual and reproductive factors and risk of breast cancer: A case-control
      study in the Fez region, Morocco.
AB  - BACKGROUND: Breast cancer is the most common cancer in women worldwide. In the
      Moroccan context, the role of well-known reproductive factors in breast cancer
      remains poorly documented. The aim of this study was to explore the relationship
      between menstrual and reproductive factors and breast cancer risk in Moroccan
      women in the Fez region. METHODS: A case-control study was conducted at the
      Hassan II University Hospital of Fez between January 2014 and April 2015. A total
      of 237 cases of breast cancer and 237 age-matched controls were included.
      Information on sociodemographic characteristics, menstrual and reproductive
      history, family history of breast cancer, and lifestyle factors was obtained
      through a structured questionnaire. Conditional logistic regression models were
      used to estimate odds ratios and 95% confidence intervals for breast cancer by
      menstrual and reproductive factors adjusted for potential confounders. RESULTS:
      Early menarche (OR = 1.60, 95% CI: 1.08-2.38) and nulliparity (OR = 3.77, 95% CI:
      1.98-7.30) were significantly related to an increased risk of breast cancer,
      whereas an early age at first full-term pregnancy was associated with a decreased
      risk of breast cancer (OR = 0.41, 95% CI: 0.25-0.65). CONCLUSION: The results of
      this study confirm the role of established reproductive factors for breast cancer
      in Moroccan women. It identified some susceptible groups at high risk of breast
      cancer. Preventive interventions and screening should focus on these groups as a
      priority. These results should be confirmed in a larger, multicenter study.

PMID- 29338059
TI  - Hemodynamic characteristics of hyperplastic remodeling lesions in cerebral
      aneurysms.
AB  - BACKGROUND & PURPOSE: Hyperplastic remodeling (HR) lesions are sometimes found on
      cerebral aneurysm walls. Atherosclerosis is the results of HR, which may cause an
      adverse effect on surgical treatment for cerebral aneurysms. Previous studies
      have demonstrated that atherosclerotic changes had a correlation with certain
      hemodynamic characteristics. Therefore, we investigated local hemodynamic
      characteristics of HR lesions of cerebral aneurysms using computational fluid
      dynamics (CFD). METHODS: Twenty-four cerebral aneurysms were investigated using
      CFD and intraoperative video recordings. HR lesions and red walls were confirmed
      on the intraoperative images, and the qualification points were determined on the
      center of the HR lesions and the red walls. The qualification points were set on
      the virtual operative images for evaluation of wall shear stress (WSS),
      normalized WSS (NWSS), oscillatory shear index (OSI), relative residence time
      (RRT), and aneurysm formation indicator (AFI). These hemodynamic parameters at
      the qualification points were compared between HR lesions and red walls. RESULTS:
      HR lesions had lower NWSS, lower AFI, higher OSI and prolonged RRT compared with
      red walls. From analysis of the receiver-operating characteristic curve for
      hemodynamic parameters, OSI was the most optimal hemodynamic parameter to predict
      HR lesions (area under the curve, 0.745; 95% confidence interval, 0.603-0.887;
      cutoff value, 0.00917; sensitivity, 0.643; specificity, 0.893; P<0.01). With
      multivariate logistic regression analyses using stepwise method, NWSS was
      significantly associated with the HR lesions. CONCLUSIONS: Although low NWSS was
      independently associated with HR lesions, OSI is the most valuable hemodynamic
      parameter to distinguish HR lesions from red walls.

PMID- 29338060
TI  - Biofeedback effect of hybrid assistive limb in stroke rehabilitation: A proof of
      concept study using functional near infrared spectroscopy.
AB  - INTRODUCTION: Robot-assisted rehabilitation has been increasingly drawing
      attention in the field of neurorehabilitation. The hybrid assistive limb (HAL) is
      an exoskeleton robot developed based on the "interactive biofeedback" theory, and
      several studies have shown its efficacy for patients with stroke. We aimed to
      investigate the mechanisms of the facilitative effect of neurorehabilitation
      using a single-joint HAL (HAL-SJ) and functional near-infrared spectroscopy
      (fNIRS). MATERIALS AND METHODS: Subacute stroke patients admitted to our hospital
      were assessed in this study for HAL eligibility. We evaluated motor-related
      cortical activity using an fNIRS system at baseline and immediately after HAL-SJ
      treatment on the same day. Cortical activity was determined through the relative
      changes in the hemoglobin concentrations. For statistical analysis, we compared
      the number of flexion/extension movements before and immediately after HAL-SJ
      treatment using paired t-test. fNIRS used both the methods of statistical
      parametric mapping and random effect analysis. RESULTS: We finally included 10
      patients (eight men, two women; mean age: 66.8 +/- 12.0 years). The mean number
      of flexion/extension movements within 15 s increased significantly from 4.2 +/-
      3.1 to 5.3 +/- 4.1 immediately after training. fNIRS showed increased cortical
      activation in the primary motor cortex of the ipsilesional hemisphere immediately
      after HAL-SJ treatment compared to the baseline condition. CONCLUSIONS: This
      study is the first to support the concept of the biofeedback effect from the
      perspective of changes in cortical activity measured with an fNIRS system. The
      biofeedback effect of HAL immediately increased the task-related cortical
      activity, and this may address the functional recovery. Further studies are
      warranted to support our findings.

PMID- 29338061
TI  - Feasibility of cell-based therapy combined with descemetorhexis for treating
      Fuchs endothelial corneal dystrophy in rabbit model.
AB  - Corneal transparency is maintained by the corneal endothelium through its pump
      and barrier function. Severe corneal endothelial damage results in dysregulation
      of water flow and eventually causes corneal haziness and deterioration of visual
      function. In 2013, we initiated clinical research of cell-based therapy for
      treating corneal decompensation. In that study, we removed an 8-mm diameter
      section of damaged corneal endothelium without removing Descemet's membrane (the
      basement membrane of the corneal endothelium) and then injected cultured human
      corneal endothelial cells (CECs) into the anterior chamber. However, Descemet's
      membrane exhibits clinically abnormal structural features [i.e., multiple
      collagenous excrescences (guttae) and thickening] in patients with Fuchs
      endothelial corneal dystrophy (FECD) and the advanced cornea guttae adversely
      affects the quality of vision, even in patients without corneal edema. The
      turnover time of cornea guttae is also not certain. Therefore, we used a rabbit
      model to evaluate the feasibility of Descemet's membrane removal in the optical
      zone only, by performing a small 4-mm diameter descemetorhexis prior to CEC
      injection. We showed that the corneal endothelium is regenerated both on the
      corneal stroma (the area of Descemet's membrane removal) and on the intact
      peripheral Descemet's membrane, based on the expression of function-related
      markers and the restoration of corneal transparency. Recovery of the corneal
      transparency and central corneal thickness was delayed in areas of Descemet's
      membrane removal, but the cell density of the regenerated corneal endothelium and
      the thickness of the central corneal did not differ between the areas with and
      without residual Descemet's membrane at 14 days after CEC injection. Here, we
      demonstrate that removal of a pathological Descemet's membrane by a small
      descemetorhexis is a feasible procedure for use in combination with cell-based
      therapy. The current strategy might be beneficial for improving visual quality
      after CEC injection as a treatment for FECD.

PMID- 29338062
TI  - An imaged-based inverse finite element method to determine in-vivo mechanical
      properties of the human trabecular meshwork.
AB  - Aim: Previous studies have shown that the trabecular meshwork (TM) is
      mechanically stiffer in glaucomatous eyes as compared to normal eyes. It is
      believed that elevated TM stiffness increases resistance to the aqueous humor
      outflow, producing increased intraocular pressure (IOP). It would be advantageous
      to measure TM mechanical properties in vivo, as these properties are believed to
      play an important role in the pathophysiology of glaucoma and could be useful for
      identifying potential risk factors. The purpose of this study was to develop a
      method to estimate in-vivo TM mechanical properties using clinically available
      exams and computer simulations. Design: Inverse finite element simulation.
      Methods: A finite element model of the TM was constructed from optical coherence
      tomography (OCT) images of a healthy volunteer before and during IOP elevation.
      An axisymmetric model of the TM was then constructed. Images of the TM at a
      baseline IOP level of 11, and elevated level of 23 mmHg were treated as the
      undeformed and deformed configurations, respectively. An inverse modeling
      technique was subsequently used to estimate the TM shear modulus (G). An
      optimization technique was used to find the shear modulus that minimized the
      difference between Schlemm's canal area in the in-vivo images and simulations.
      Results: Upon completion of inverse finite element modeling, the simulated area
      of the Schlemm's canal changed from 8,889 um2 to 2,088 um2, similar to the
      experimentally measured areal change of the canal (from 8,889 um2 to 2,100 um2).
      The calculated value of shear modulus was found to be 1.93 kPa, (implying an
      approximate Young's modulus of 5.75 kPa), which is consistent with previous ex
      vivo measurements. Conclusion: The combined imaging and computational simulation
      technique provides a unique approach to calculate the mechanical properties of
      the TM in vivo without any surgical intervention. Quantification of such
      mechanical properties will help us examine the mechanistic role of TM
      biomechanics in the regulation of IOP in healthy and glaucomatous eyes.

PMID- 29338063
TI  - Formalizing Knowledge in Multi-Scale Agent-Based Simulations.
AB  - Multi-scale, agent-based simulations of cellular and tissue biology are
      increasingly common. These simulations combine and integrate a range of
      components from different domains. Simulations continuously create, destroy and
      reorganize constituent elements causing their interactions to dynamically change.
      For example, the multi-cellular tissue development process coordinates molecular,
      cellular and tissue scale objects with biochemical, biomechanical, spatial and
      behavioral processes to form a dynamic network. Different domain specific
      languages can describe these components in isolation, but cannot describe their
      interactions. No current programming language is designed to represent in human
      readable and reusable form the domain specific knowledge contained in these
      components and interactions. We present a new hybrid programming language
      paradigm that naturally expresses the complex multi-scale objects and dynamic
      interactions in a unified way and allows domain knowledge to be captured,
      searched, formalized, extracted and reused.

PMID- 29338065
TI  - Corrigendum to "Tooth Reattachment and Palatal Veneer on a Multidisciplinary
      Approach of Crown Fractures in Upper Central Incisors".
AB  - [This corrects the article DOI: 10.1155/2017/4702635.].

PMID- 29338064
TI  - Reflections on 15 Years in the Global Tobacco Trenches.
AB  - This paper is based on my 2017 Research Laureate Presentation at the Annual
      Scientific Meeting of the American Academy of Health Behavior in Tucson, Arizona.
      It provides a brief overview of the history of the smoking epidemic, and
      describes my work in global tobacco control, focusing on my experiences over the
      last 15 years as a co-founder and intervention director of the Syrian Center for
      Tobacco Studies (SCTS) in Aleppo, Syria. The SCTS is an NIH-funded research
      center that draws on a broad range of complementary expertise and resources from
      developed and developing nations to address the tobacco epidemic in the Arab
      World. The SCTS strives to serve as a model of scientific excellence and
      commitment to the health of people in the Middle East and beyond. Major research
      streams using qualitative, epidemiological, clinical lab, and intervention
      methodologies are reviewed, along with some of the successes and challenges
      encountered since the SCTS's founding.

PMID- 29338066
TI  - Endoscopic scoring indices for evaluation of disease activity in ulcerative
      colitis.
AB  - BACKGROUND: Endoscopic assessment of mucosal disease activity is routinely used
      to determine eligibility and response to therapy in clinical trials of ulcerative
      colitis. The operating properties of the existing endoscopic scoring indices are
      unclear. OBJECTIVES: A systematic review was undertaken to evaluate the
      development and operating characteristics of endoscopic scoring indices for the
      evaluation of ulcerative colitis. SEARCH METHODS: We searched MEDLINE, Embase and
      CENTRAL from inception to 5 July 2016. We also searched references and conference
      proceedings (Digestive Disease Week, United European Gastroenterology Week,
      European Crohn's and Colitis Organization). SELECTION CRITERIA: Any study design
      (e.g. randomized controlled trials, cohort studies, case series) that evaluated
      endoscopic indices for evaluation of ulcerative colitis disease activity were
      considered for inclusion. Eligible participants were adult patients (> 16 years),
      diagnosed with ulcerative colitis using conventional clinical, radiologic and
      endoscopic criteria. DATA COLLECTION AND ANALYSIS: Two authors independently
      reviewed the studies identified from the literature search. These authors also
      independently extracted and recorded data on the number of patients enrolled;
      number of patients per treatment arm; patient characteristics including age and
      gender distribution; endoscopic index; and outcomes such as reliability (intra
      rater and inter-rater), validity (content, construct, criterion), responsiveness
      and feasibility. Any disagreements regarding study inclusion or data extraction
      were resolved by discussion and consensus with a third author. Risk of bias was
      assessed by determining whether assessors were blinded to clinical information
      and whether assessors scored the endoscopic index independently. We also assessed
      the methodological quality of the validation studies using the COSMIN checklist
      MAIN RESULTS: A total of 23 reports of 20 studies met the pre-defined inclusion
      criteria and were included in the review. Of the 20 included validation studies,
      19 endoscopic scoring indices were assessed, including the Azzolini
      Classification, Baron Score, Blackstone Endoscopic Interpretation, Chinese
      Grading System of Ulcerative Colitis, Endoscopic Activty Index, Jeroen Score,
      Magnifying Colonoscopy Grade, Matts Score, Mayo Clinic Endoscopic Subscore,
      Modified Baron Score, Modified Mayo Clinic Endoscopic Subscore, Osada Score,
      Rachmilewtiz Endoscopic Score, St. Mark's Index, Ulcerative Colitis Colonoscopic
      Index of Serverity (UCCIS), endoscopic component of the Ulcerative Colitis
      Disease Activity Index (UCDAI), Ulcerative Colitis Endoscopic Index of Severity
      (UCEIS), Witts Sigmoidoscopic Score and Watson Grade. The individuals who
      performed the endoscopic scoring were blinded to clinical and/or histologic
      information in ten of the included studies, not blinded to clinical and/or
      histologic information in one of the included studies, and it was unclear whether
      blinding occurred in the remaining nine included studies. Independent observation
      was confirmed in four of the included studies, unclear in five of the included
      studies, and non-applicable (since inter-rater reliability was not assessed) in
      the remaining eleven included studies. The methodological quality (COSMIN
      checklist) of most of the included studies was rated as 'good' or 'excellent'.
      One study that assessed responsiveness was rated as 'fair'. The inter-rater
      reliability of nine endoscopic scoring indices including the Baron Score,
      Blackstone Endoscopic Interpretation, Endoscopic Activity Index, Matts Score,
      Mayo Clinic Endoscopic Subscore, Osada Score, UCCIS, UCEIS, Watson Grade was
      assessed in seven studies, with estimates of correlation, k, ranging from 0.44 to
      0.97. The iIntra-rater reliability of seven endoscopic scoring indices including
      the Baron Score, Blackstone Endoscopic Interpretation, Matts Score, Mayo Clinic
      Endoscopic Subscore, Osada Score, UCCIS and UCEIS was assessed in three studies,
      with estimates of correlation, k, ranging from 0.41 to 0.86. No studies assessed
      content validity. Three studies evaluated the criterion validity of three
      endoscopic scoring indices including the Rachmilewitz Endoscopic Score,
      Magnifying Colonoscopy Grade and the UCCIS. These indices were correlated with
      objective markers of disease activity including albumin, blood leukocytes, C
      reactive protein, fecal calprotectin, hemoglobin, mucosal interleukin-8
      concentration and platelet count. Correlation estimates ranged from r = -0.19 to
      0.83. Thirteen endoscopic scoring indices were tested for construct validity in
      13 studies. Estimates of correlation between the endoscopic scoring indices and
      other measures of disease activity ranged from r = 0.27 to 0.93. Two studies
      explored the responsiveness of four endoscopic scoring indices including the Mayo
      Endoscopic Subscore, Modified Baron Score, Modified Mayo Endoscopic Subscore and
      UCEIS. One study concluded that the Modified Baron Score, Modified Mayo
      Endoscopic Subscore and UCEIS had similar responsiveness for detecting disease
      change in ulcerative colitis. The other included study concluded that the UCEIS
      may be the most accurate endoscopic scoring tool. None of the included studies
      formally assessed feasibility. AUTHORS' CONCLUSIONS: While the UCEIS, UCCIS and
      Mayo Clinic Endoscopic Subscore have undergone extensive validation, none of
      these instruments have been fully validated and only two studies assessed
      responsiveness. Further research on the operating properties of these indices is
      needed given the lack of a fully-validated endoscopic scoring instrument for the
      evaluation of disease activity in ulcerative colitis.

PMID- 29338067
TI  - The influence of delayed cord clamping and cord milking on inflammatory cytokines
      in umbilical vein and neonatal circulation.
AB  - INTRODUCTION: The purpose of the present study was to compare the levels of tumor
      necrosis factor alpha (TNF-alpha), and interleukins (IL) 1, 6, 8 and 10 in the
      umbilical cord and neonatal circulation among neonates with early and late cord
      clamping. MATERIAL AND METHODS: A consecutive series of 76 cases of uncomplicated
      pregnancy and an uneventful parturition was evaluated. In 40 cases, delayed cord
      clamping was used and in the remaining 36, early cord clamping was practiced.
      Blood samples were collected from the umbilical vein immediately after cord
      clamping and at 24 h from the median cubital or basilic vein of the neonate.
      RESULTS: Significant differences were noted in the hematocrit and hemoglobin
      levels at 24 h that favored delayed clamping. None of the evaluated markers of
      inflammation differ between the two groups. Spearman's rho revealed a significant
      correlation between umbilical cord TNF-alpha and TNF-alpha neonatal values at 24
      h (r = 0.551, p = 0.022) in the early clamped group. Significant correlations
      were also noted between umbilical cord TNF-alpha and TNF-alpha neonatal values at
      24 h (r = 0.728, p = 0.001), umbilical cord IL-10 and neonatal IL-10 at 24 h (r =
      0.487, p = 0.047) and umbilical cord IL-1b and neonatal IL-1b at 24 h (r = 0.516,
      p = 0.034). CONCLUSIONS: Delayed cord clamping or cord milking does not alter the
      levels of inflammatory cytokines in cord blood and neonatal serum. Future studies
      should evaluate the impact of delayed cord clamping in selected high-risk
      pregnancies.

PMID- 29338068
TI  - Single and combined effects of plant-derived and synthetic cannabinoids on
      cognition and cannabinoid-associated withdrawal signs in mice.
AB  - BACKGROUND AND PURPOSE: It has been suggested that the non-euphorogenic
      phytocannabinoid cannabidiol (CBD) can ameliorate adverse effects of Delta9 
      tetrahydrocannabinol (THC). We determined whether CBD ameliorates cognitive
      deficits and withdrawal signs induced by cannabinoid CB1 /CB2 receptor agonists
      or produces these pharmacological effects on its own. EXPERIMENTAL APPROACH: The
      effects of THC or the CB1 /CB2 receptor full agonist WIN55212 alone, CBD alone or
      their combination were tested across a range of doses. Cognitive effects were
      assessed in C57BL/6 mice in a conditional discrimination task and in the Barnes
      maze. Cannabinoid withdrawal signs were assessed following precipitated
      withdrawal by acute administration of the CB1 receptor antagonist SR141716, the 5
      HT1A receptor antagonist WAY100635, the TRPV1 receptor antagonist capsazepine or
      the adenosine A2A receptor antagonist SCH58261. KEY RESULTS: THC produced
      significant motor and cognitive impairment in the Barnes maze task, none of which
      were attenuated by the addition of CBD. CBD alone did not affect cognitive
      performance. Precipitation of withdrawal signs by SR141716 occurred in mice
      chronically treated with THC or WIN55,212. These withdrawal signs were not
      attenuated by addition of chronic CBD. Chronic treatment with CBD alone did not
      induce withdrawal signs precipitated by SR141716 or WAY100635. Chronic CBD
      treatment also produced anxiolysis, which was not altered by attempting to
      precipitate withdrawal-induced anxiety with a range of antagonists. CONCLUSIONS
      AND IMPLICATIONS: CBD as a monotherapy may prove to be a safer pharmacological
      agent, than CB1 receptor agonists alone or in combination with CBD, for the
      treatment of several disorders.

PMID- 29338069
TI  - Cesarean scar niche and uterotomy closure technique.

PMID- 29338071
TI  - The financial burden and distress of patients with cancer: Understanding and
      stepping-up action on the financial toxicity of cancer treatment.
AB  - "Financial toxicity" has now become a familiar term used in the discussion of
      cancer drugs, and it is gaining traction in the literature given the high price
      of newer classes of therapies. However, as a phenomenon in the contemporary
      treatment and care of people with cancer, financial toxicity is not fully
      understood, with the discussion on mitigation mainly geared toward interventions
      at the health system level. Although important, health policy prescriptions take
      time before their intended results manifest, if they are implemented at all. They
      require corresponding strategies at the individual patient level. In this review,
      the authors discuss the nature of financial toxicity, defined as the objective
      financial burden and subjective financial distress of patients with cancer, as a
      result of treatments using innovative drugs and concomitant health services. They
      discuss coping with financial toxicity by patients and how maladaptive coping
      leads to poor health and nonhealth outcomes. They cover management strategies for
      oncologists, including having the difficult and urgent conversation about the
      cost and value of cancer treatment, availability of and access to resources, and
      assessment of financial toxicity as part of supportive care in the provision of
      comprehensive cancer care. CA Cancer J Clin 2018;68:153-165. (c) 2018 American
      Cancer Society.

PMID- 29338070
TI  - The use of chemogenetics in behavioural neuroscience: receptor variants,
      targeting approaches and caveats.
AB  - The last decade has seen major advances in neuroscience tools allowing us to
      selectively modulate cellular pathways in freely moving animals. Chemogenetic
      approaches such as designer receptors exclusively activated by designer drugs
      (DREADDs) permit the remote control of neuronal function by systemic drug
      administration. These approaches have dramatically advanced our understanding of
      the neural control of behaviour. Here, we review the different techniques and
      genetic approaches available for the restriction of chemogenetic receptors to
      defined neuronal populations. We highlight the use of a dual virus approach to
      target specific circuitries and the effectiveness of different routes of
      administration of designer drugs. Finally, we discuss the potential caveats
      associated with DREADDs including off-target effects of designer drugs, the
      effects of chronic chemogenetic receptor activation and the issue of collateral
      projections associated with DREADD activation and inhibition.

PMID- 29338072
TI  - Targeting HER2 in colorectal cancer: The landscape of amplification and short
      variant mutations in ERBB2 and ERBB3.
AB  - BACKGROUND: In contrast to lung cancer, few precision treatments are available
      for colorectal cancer (CRC). One rapidly emerging treatment target in CRC is
      ERBB2 (human epidermal growth factor receptor 2 [HER2]). Oncogenic alterations in
      HER2, or its dimerization partner HER3, can underlie sensitivity to HER2-targeted
      therapies. METHODS: In this study, 8887 CRC cases were evaluated by comprehensive
      genomic profiling for genomic alterations in 315 cancer-related genes, tumor
      mutational burden, and microsatellite instability. This cohort included both
      colonic (7599 cases; 85.5%) and rectal (1288 cases; 14.5%) adenocarcinomas.
      RESULTS: A total of 569 mCRCs were positive for ERBB2 (429 cases; 4.8%) and/or
      ERBB3 (148 cases; 1.7%) and featured ERBB amplification, short variant
      alterations, or a combination of the 2. High tumor mutational burden (>=20
      mutations/Mb) was significantly more common in ERBB-mutated samples, and ERBB3
      mutated CRCs were significantly more likely to have high microsatellite
      instability (P<.002). Alterations affecting KRAS (27.3%) were significantly
      underrepresented in ERBB2-amplified samples compared with wild-type CRC samples
      (51.8%), and ERBB2- or ERBB3-mutated samples (49.0% and 60.8%, respectively)
      (P<.01). Other significant differences in mutation frequency were observed for
      genes in the PI3K/MTOR and mismatch repair pathways. CONCLUSIONS: Although
      observed less often than in breast or upper gastrointestinal carcinomas,
      indications for which anti-HER2 therapies are approved, the percentage of CRC
      with ERBB genomic alterations is significant. Importantly, 32% of ERBB2-positive
      CRCs harbor short variant alterations that are undetectable by routine
      immunohistochemistry or fluorescence in situ hybridization testing. The success
      of anti-HER2 therapies in ongoing clinical trials is a promising development for
      patients with CRC. Cancer 2018;124:1358-73. (c) 2018 Foundation Medicine, Inc.
      Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

PMID- 29338073
TI  - Impact of time to testosterone rebound and comorbidity on the risk of cause
      specific mortality in men with unfavorable-risk prostate cancer.
AB  - BACKGROUND: Herein, the authors evaluated how the time to testosterone rebound
      (TTR) after radiotherapy (RT) and 6 months of androgen deprivation therapy (ADT)
      impacted the risk of prostate cancer-specific mortality (PCSM) and cardiovascular
      specific mortality (CVM) among men with varying comorbidity extent. METHODS:
      Between 1995 and 2001, a total of 206 men who were randomized to receive RT
      either alone or with 6 months of ADT for unfavorable-risk PC and who had a
      comorbidity score assigned using the Adult Comorbidity Evaluation 27 metric
      comprised the study cohort. Multivariable competing risk regression was used to
      evaluate the impact of and possible interaction between comorbidity and TTR on
      PCSM and CVM. RESULTS: After a median follow-up of 18.19 years, 30 men (18.6%),
      39 men (24.2%), and 92 men (57.1%), respectively, had died of PC, CV disease, or
      other causes. As TTR increased, PCSM significantly decreased in men with no or
      minimal (adjusted hazard ratio [AHR], 0.53, 95% confidence interval [95% CI],
      0.34-0.84 [P =.007]) and moderate to severe (AHR, 0.37; 95% CI, 0.14-0.99 [P =
      .048]) comorbidity. However, increasing TTR significantly increased the risk of
      CVM among men with moderate to severe comorbidity (AHR, 1.87; 95% CI, 1.40-2.49
      [P <.001]), but not those with no or minimal comorbidity (AHR, 0.86; 95% CI, 0.57
      1.29 [P =.46]), leading to a significant interaction between TTR and comorbidity
      (P = .001). CONCLUSIONS: The results of the current study indicate that
      considering an intermittent course of ADT such that the TTR approaches 18 months,
      instead of continuous long-term administration of ADT, in men with moderate to
      severe comorbidity and high-risk PC may reduce the increased risk of CVM without
      increasing the risk of PCSM. Cancer 2018;124:1391-9. (c) 2018 American Cancer
      Society.

PMID- 29338075
TI  - Liver kinase B1/AMP-activated protein kinase-mediated regulation by
      gentiopicroside ameliorates P2X7 receptor-dependent alcoholic hepatosteatosis.
AB  - BACKGROUND AND PURPOSE: Regulating P2X7 receptor-mediated activation of NLRP3
      inflammasomes could be a therapeutic strategy to treat alcoholic hepatosteatosis.
      We investigated whether this process was modulated by gentiopicroside, the main
      active secoiridoid glycoside from Gentiana manshurica Kitagawa. EXPERIMENTAL
      APPROACH: In vivo models of acute and chronic alcoholic hepatosteatosis were
      established by intragastrically administered ethanol or using chronic plus binge
      ethanol feeding of Lieber-DeCarli liquid diet to male C57BL/6 mice. In vitro,
      HepG2 cells were treated with ethanol. RAW 264.7 macrophages and murine bone
      marrow-derived macrophages (BMDMs) were stimulated with LPS and ATP. KEY RESULTS:
      In both the acute and chronic alcohol-induced mouse hepatosteatosis models,
      gentiopicroside decreased serum aminotransferases and triglyceride accumulation.
      Up-regulated SREBP1, down-regulated PPARalpha and phosphorylated acetyl-CoA
      carboxylase caused by acute and chronic alcohol feeding were modulated by
      gentiopicroside, through the elevation of LKB1 and AMPK. Suppression of P2X7
      receptor-NLRP3 activation by gentiopicroside inhibited IL-1beta production. In
      ethanol-exposed HepG2 cells, gentiopicroside reduced lipogenesis and promoted
      lipid oxidation via activation of P2X7 receptor-NLRP3 inflammasomes. Genetic or
      pharmacological blockade of P2X7 receptors enhanced AMPK activity and reduced
      SREBP1 expression in ethanol-treated HepG2 cells. Gentiopicroside down-regulated
      P2X7 receptor-mediated inflammatory responses in LPS/ATP-stimulated RAW 264.7
      macrophages and BMDMs. IL-1beta from macrophages accelerated lipid accumulation
      in hepatocytes. Depleting macrophages by clodronate liposomes ameliorated
      alcoholic hepatosteatosis, and it was further alleviated by gentiopicroside.
      CONCLUSIONS AND IMPLICATIONS: Activation of LKB1/AMPK signalling by
      gentiopicroside was mediated by the P2X7 receptor-NLRP3 inflammasome, suggesting
      the therapeutic value of blocking P2X7 receptors in the treatment of alcoholic
      hepatosteatosis.

PMID- 29338074
TI  - Adaptive immune education by gut microbiota antigens.
AB  - Host-microbiota mutualism has been established during long-term co-evolution. A
      diverse and rich gut microbiota plays an essential role in the development and
      maturation of the host immune system. Education of the adaptive immune
      compartment by gut microbiota antigens is important in establishing immune
      balance. In particular, a critical time frame immediately after birth provides a
      'window of opportunity' for the development of lymphoid structures,
      differentiation and maturation of T and B cells and, most importantly,
      establishment of immune tolerance to gut commensals. Depending on the
      colonization niche, antigen type and metabolic property of different gut
      microbes, CD4 T-cell responses vary greatly, which results in differentiation
      into distinct subsets. As a consequence, certain bacteria elicit effector-like
      immune responses by promoting the production of pro-inflammatory cytokines such
      as interferon-gamma and interleukin-17A, whereas other bacteria favour the
      generation of regulatory CD4 T cells and provide help with gut homeostasis. The
      microbiota have profound effects on B cells also. Gut microbial exposure leads to
      a continuous diversification of B-cell repertoire and the production of T
      dependent and -independent antibodies, especially IgA. These combined effects of
      the gut microbes provide an elegant educational process to the adaptive immune
      network. Contrariwise, failure of this process results in a reduced homeostasis
      with the gut microbiota, and an increased susceptibility to various immune
      disorders, both inside and outside the gut. With more definitive microbial-immune
      relations waiting to be discovered, modulation of the host gut microbiota has a
      promising future for disease intervention.

PMID- 29338077
TI  - Blenderized Enteral Nutrition Diet Study: Feasibility, Clinical, and Microbiome
      Outcomes of Providing Blenderized Feeds Through a Gastric Tube in a Medically
      Complex Pediatric Population.
AB  - BACKGROUND: Chronically ill children often require feeding via gastrostomy tubes
      (G-tubes). Commercial formula is most commonly used for enteral feeding; however,
      caregivers have been requesting blenderized tube feeds (BTFs) as an alternative.
      The objective of this study was to evaluate the feasibility of using BTFs in a
      medically complex pediatric population and assess their impact on clinical
      outcomes, as well as the microbiota. METHODS: Twenty pediatric participants were
      included. Participants were G-tube dependent and receiving >=75% of their daily
      energy requirements from commercial formula. Over 4 weeks, participants were
      transitioned from commercial formula to BTF and were monitored for 6 months for
      changes in nutrient intake, gastrointestinal symptoms, oral feeding, medication
      use, and caregiver perceptions. Changes to intestinal microbiota were monitored
      by 16S rDNA-based sequencing. RESULTS: Transition onto BTF was feasible in 17
      participants, and 1 participant transitioned to oral feeds. Participants required
      50% more calories to maintain their body mass index while on BTFs compared with
      commercial formula. BTF micronutrient content was superior to commercial formula.
      Prevalence of vomiting and use of acid-suppressive agents significantly decreased
      on BTFs. Stool consistency and frequency remained unchanged, while stool softener
      use increased. The bacterial diversity and richness in stool samples
      significantly increased, while the relative abundance of Proteobacteria
      decreased. Caregivers were more satisfied with BTFs and unanimously indicated
      they would recommend BTFs. CONCLUSION: Initiation and maintenance of BTFs is not
      only feasible in a medically complex pediatric population but can also be
      associated with improved clinical outcomes and increased intestinal bacterial
      diversity.

PMID- 29338078
TI  - Bladder cancer and the National Cancer Data Base: New insight or misinformation?

PMID- 29338076
TI  - Hypoxia-inducible transcription factors, HIF1A and HIF2A, increase in aging
      mucosal tissues.
AB  - Hypoxia (i.e. oxygen deprivation) activates the hypoxia-signalling pathway,
      primarily via hypoxia-inducible transcription factors (HIF) for numerous target
      genes, which mediate angiogenesis, metabolism and coagulation, among other
      processes to try to replenish tissues with blood and oxygen. Hypoxia signalling
      dysregulation also commonly occurs during chronic inflammation. We sampled
      gingival tissues from rhesus monkeys (Macaca mulatta; 3-25 years old) and total
      RNA was isolated for microarray analysis. HIF1A, HIF1B and HIF2A were
      significantly different in healthy aged tissues, and both HIF1A and HIF3A were
      positively correlated with aging. Beyond these transcription factor alterations,
      analysis of patterns of gene expression involved in hypoxic changes in tissues
      showed specific increases in metabolic pathway hypoxia-inducible genes, whereas
      angiogenesis pathway gene changes were more variable in healthy aging tissues
      across the animals. With periodontitis, aging tissues showed decreases in
      metabolic gene expression related to carbohydrate/lipid utilization (GBE1, PGAP1,
      TPI1), energy metabolism and cell cycle regulation (IER3, CCNG2, PER1), with up
      regulation of transcription genes and cellular proliferation genes (FOS, EGR1,
      MET, JMJD6) that are hypoxia-inducible. The potential clinical implications of
      these results are related to the epidemiological findings of increased
      susceptibility and expression of periodontitis with aging. More specifically the
      findings describe that hypoxic stress may exist in aging gingival tissues before
      documentation of clinical changes of periodontitis and, so, may provide an
      explanatory molecular risk factor for an elevated capacity of the tissues to
      express destructive processes in response to changes in the microbial biofilms
      characteristic of a more pathogenic microbial challenge.

PMID- 29338079
TI  - Nutrition Delivery and Growth Outcomes in Infants With Gastroschisis.
AB  - BACKGROUND: We aimed to describe nutrient intake and growth in infants with
      gastroschisis and identify factors associated with impaired growth. METHODS:
      Retrospective study of neonates who underwent gastroschisis repair from 2010 to
      2015. Nutrient intake and weight-for-age z scores (WAZ) were recorded. RESULTS:
      Data from 60 eligible infants with median (Q1, Q3) gestational age of 36 weeks
      (35, 37) and birth weight 2418 g (2098, 2665) were analyzed. Median WAZ decreased
      from -0.71 (-1.08, -0.17) at birth to -1.08 (-1.58, -0.63) at discharge (P <
      .001); 30% experienced a >1.0 decline in WAZ. Parenteral nutrition (PN) was
      initiated soon after birth, and 14 (23%) patients had severe intestinal failure.
      Fourteen patients (23%) experienced central line-associated bloodstream infection
      (CLABSI) at a rate of 5.0 per 1000 catheter days. Factors independently
      associated with lower discharge WAZ and greater WAZ decline were CLABSI (P = .02)
      and prematurity (P = .02). By day 7, energy and protein intake were 90-100
      kcal/kg/day and 3 g/kg/day, respectively. Median age to achieve enteral autonomy
      was 36 days (22, 82). Atresias, CLABSI, prematurity, and staged closure were
      associated with delayed enteral autonomy (P < .01). Among 34 patients with 1-year
      follow-up, WAZ improved from -1.16 (-1.74, -0.65) at discharge to 0.19 (-0.80,
      0.61) at 12 months (P < .001). CONCLUSION: Infants with gastroschisis are
      dependent on PN and have a significant decline in WAZ during their hospital stay,
      predicted by prematurity and CLABSI. Efforts to prevent CLABSI and optimize
      enteral autonomy must be prioritized in this cohort.

PMID- 29338080
TI  - Phase 1 trial evaluating cisplatin, gemcitabine, and veliparib in 2 patient
      cohorts: Germline BRCA mutation carriers and wild-type BRCA pancreatic ductal
      adenocarcinoma.
AB  - BACKGROUND: A phase 1 trial was used to evaluate a combination of cisplatin,
      gemcitabine, and escalating doses of veliparib in patients with untreated
      advanced pancreatic ductal adenocarcinoma (PDAC) in 2 cohorts: a germline BRCA1/2
      mutated (BRCA+) cohort and a wild-type BRCA (BRCA-) cohort. The aims were to
      determine the safety, dose-limiting toxicities (DLTs), maximum tolerated dose,
      and recommended phase 2 dose (RP2D) of veliparib combined with cisplatin and
      gemcitabine and to assess the antitumor efficacy (Response Evaluation Criteria in
      Solid Tumors, version 1.1) and overall survival. METHODS: Gemcitabine and
      cisplatin were dosed at 600 and 25 mg/m2 , respectively, over 30 minutes on days
      3 and 10 of a 21-day cycle. Four dose levels of veliparib were evaluated: 20
      (dose level 0), 40 (dose level 1), and 80 mg (dose level 2) given orally twice
      daily on days 1 to 12 and 80 mg given twice daily on days 1 to 21 (dose level 2A
      [DL2A]). RESULTS: Seventeen patients were enrolled: 9 BRCA+ patients, 7 BRCA-
      patients, and 1 patient with an unknown status. DLTs were reached at DL2A (80 mg
      twice daily on days 1 to 21). Two of the 5 patients in this cohort (40%)
      experienced grade 4 neutropenia and thrombocytopenia. Two grade 5 events occurred
      on protocol. The objective response rate in the BRCA+ cohort was 7 of 9 (77.8%).
      The median overall survival for BRCA+ patients was 23.3 months (95% confidence
      interval [CI], 3.8-30.2 months). The median overall survival for BRCA- patients
      was 11 months (95% CI, 1.5-12.1 months). CONCLUSIONS: The RP2D of veliparib was
      80 mg by mouth twice daily on days 1 to 12 in combination with cisplatin and
      gemcitabine; the DLT was myelosuppression. Substantial antitumor activity was
      seen in BRCA+ PDAC. A randomized phase 2 trial is currently evaluating cisplatin
      and gemcitabine with and without veliparib for BRCA+ PDAC (NCT01585805). Cancer
      2018;124:1374-82. (c) 2018 American Cancer Society.

PMID- 29338081
TI  - Nonsurgical premature menopause and reproductive implications in survivors of
      childhood cancer: A report from the Childhood Cancer Survivor Study.
AB  - BACKGROUND: Survivors of childhood cancer are at risk of nonsurgical premature
      menopause (NSPM). To the authors' knowledge, risk factors for NSPM and its impact
      on reproduction remain poorly defined. METHODS: The menopausal status of 2930
      survivors diagnosed between 1970 and 1986 (median age, 6 years [range, birth-20
      years]) who were aged > 18 years at the time of the current study (median age, 35
      years [range, 18-58 years]) was compared with 1399 siblings. NSPM was defined as
      the cessation of menses >=6 months in duration occurring 5 years after diagnosis
      and before age 40 that was not due to pregnancy, surgery, or medications. Among
      survivors, multivariable logistic regression identified risk factors for NSPM.
      Pregnancy and live birth rates were compared between survivors with and without
      NSPM. RESULTS: A total of 110 survivors developed NSPM (median age, 32 years
      [range, 16-40 years]), with a prevalence at age 40 years of 9.1% (95% confidence
      interval [95% CI], 4.9%-17.2%); the odds ratio (OR) was 10.5 (95% CI, 4.2-26.3)
      compared with siblings. Independent risk factors included exposure to a
      procarbazine dose >=4000 mg/m2 (OR, 8.96 [95% CI, 5.02-16.00]), any dose of
      ovarian radiation (OvRT) (OvRT < 500 cGy: OR, 2.73 [95% CI, 1.33-5.61] and OvRT
      >= 500 cGy: OR, 8.02 [95% CI, 2.81-22.85]; referent RT, 0), and receipt of a stem
      cell transplantation (OR, 6.35; 95% CI, 1.19-33.93). Compared with survivors
      without NSPM, those who developed NSPM were less likely to ever be pregnant (rate
      ratio, 0.49; 95% CI, 0.27-0.80) or to have a live birth (rate ratio, 0.42; 95%
      CI, 0.19-0.79) between ages 31 and 40 years. CONCLUSIONS: Survivors of childhood
      cancer are at risk of NSPM associated with lower rates of live birth in their
      30s. Those at risk should consider fertility preservation if they anticipate
      delaying childbearing. Cancer 2018;124:1044-52. (c) 2018 American Cancer Society.

PMID- 29338082
TI  - Racial/ethnic differences in thyroid cancer incidence in the United States, 2007
      2014.
AB  - BACKGROUND: Small tumor diagnostic tools including ultrasound-guided fine needle
      aspiration (FNA) and computed tomography (CT) could be causing rising and
      racially/ethnically different thyroid cancer incidence rates due to variable
      overdiagnosis of indolent tumors. Papillary tumors and <40 mm tumors are most
      likely to be overdiagnosed as indolent tumors by FNA and CT. METHODS: Age
      adjusted incidence rates (AAIRs) for the years 2007-2014 were calculated for
      race/ethnicity (white, Hispanic, Asian, African American, Native American) by
      patient/tumor characteristics for microscopically confirmed malignant thyroid
      cancer cases in the Surveillance, Epidemiology, and End Results Program 18
      database (SEER 18; N = 93,607). Multivariate analysis determined cancer patients'
      odds ratios of diagnosis with papillary thyroid carcinoma (vs other histologies)
      and tumors <40 mm (vs >=40 mm). RESULTS: For both males and females, there were
      statistically significant differences in incidence rates between race/ethnicity,
      with whites having the highest AAIRs and African Americans the lowest AAIRs.
      Among thyroid cancer patients, tumor size and histology differed significantly by
      race and insurance coverage after controlling for age, sex, stage, and tumor
      sequence. Non-whites with thyroid cancer (vs whites) were less associated with
      small tumors (odds ratio [OR], 0.51-0.79; P < .0001). Medicaid and uninsured
      patients with thyroid cancer were less associated with tumors <40 mm (OR, 0.55
      0.71; 95% confidence interval [CI], 0.49-0.76) and papillary carcinoma (OR, 0.86;
      95% CI, 0.80-0.93). CONCLUSION: The diagnosis of small tumors is occurring at
      greater rates in whites (vs non-whites) and insured (vs Medicaid and uninsured)
      patients; consequently, these groups may be vulnerable to unnecessary tests and
      treatments or potentially aided by early detection. Guidelines that define
      postdetection interventions may be needed to limit the overtreatment of indolent
      and small papillary carcinomas. Cancer 2018;124:1483-91. (c) 2018 American Cancer
      Society.

PMID- 29338084
TI  - Importance of B cells to development of regulatory T cells and prolongation of
      tissue allograft survival in recipients receiving autologous bone marrow
      transplantation.
AB  - We previously showed that congenic bone marrow transplantation (BMTx) post
      myeloablation augmented tissue allograft survival in association with increased
      regulatory T (Treg) cells of both host and bone marrow donor origin. Regulatory B
      (Breg) cells can also modulate T-cell immunity and B cells may be implicated in
      the development of Treg cells. Accordingly, we explored the effect of B-cell
      depletion in vivo on augmented graft survival post BMTx. C57BL/6 mice received
      BALB/c skin allografts followed 7 days later by myeloablation using
      cyclophosphamide and busulphan. Mice then received T-cell-depleted bone marrow
      from CD45.1 congenic donors, and ongoing immunosuppression with rapamycin (to day
      28 after BMTx). Control mice received cyclophosphamide and busulphan followed by
      rapamycin, but not congenic bone marrow. At different times post BMTx, mice
      received B-cell-depleting antibody treatment, and the effect on both skin graft
      survival, and induction of Treg cells was assessed. BMTx resulted in
      significantly prolonged skin graft survival versus control mice, in association
      with attenuated donor-specific alloreactivity relative to controls, increased
      splenic Treg cells and significantly diminished anti-donor IgG. In mice receiving
      infusion of B-depleting antibodies for 12 days from day 15 post BMTx, both graft
      survival and Treg cell activity were diminished, particularly for functional Treg
      cells of donor origin. Adoptive transfer of Breg cells from mice harvested at 15
      days post BMTx prolonged survival in naive transplanted mice and increased Treg
      cell levels. Thus, autologous BMTx augmentation of graft survival is dependent in
      part upon a population of Breg cells that can modulate the function of donor
      derived Treg cells.

PMID- 29338083
TI  - Androgen-deprivation therapy, dementia, and cognitive dysfunction in men with
      prostate cancer: How much smoke and how much fire?
AB  - Androgen-deprivation therapy (ADT) remains the cornerstone of management for
      patients with metastatic prostate cancer. Although the toxicities of ADT are well
      established, there is increasing controversy surrounding the association between
      cognitive dysfunction and the receipt of ADT, with some evidence suggesting an
      increased risk of dementia. The authors conducted a literature search to identify
      pertinent clinical studies in this field. This general review outlines the key
      findings and discusses the relative strengths and weaknesses when drawing
      conclusions about the risk of cognitive dysfunction or dementia with ADT use.
      Cancer 2018;124:1326-34. (c) 2018 American Cancer Society.

PMID- 29338085
TI  - The century experiment: the first twenty years of UC Davis' Mediterranean
      agroecological experiment.
AB  - The Century Experiment at the Russell Ranch Sustainable Agriculture Facility at
      the University of California, Davis provides long-term agroecological data from
      row crop systems in California's Central Valley starting in 1993. The Century
      Experiment was initially designed to study the effects of a gradient of water and
      nitrogen availability on soil properties and crop performance in ten different
      cropping systems to measure tradeoffs and synergies between agricultural
      productivity and sustainability. Currently systems include 11 different cropping
      systems-consisting of four different crops and a cover crop mixture-and one
      native grass system. This paper describes the long-term core data from the
      Century Experiment from 1993-2014, including crop yields and biomass, crop
      elemental contents, aerial-photo-based Normalized Difference Vegetation Index
      data, soil properties, weather, chemical constituents in irrigation water, winter
      weed populations, and operational data including fertilizer and pesticide
      application amounts and dates, planting dates, planting quantity and crop
      variety, and harvest dates. This data set represents the only known long-term set
      of data characterizing food production and sustainability in irrigated and
      rainfed Mediterranean annual cropping systems. There are no copyright
      restrictions associated with the use of this dataset.

PMID- 29338086
TI  - Cardiometabolic risk factors and survival after breast cancer in the Women's
      Health Initiative.
AB  - BACKGROUND: Few studies have examined the relationship between cardiometabolic
      risk factors linked to metabolic syndrome and mortality among women with breast
      cancer. METHODS: We used the Women's Health Initiative to evaluate the
      relationship between cardiometabolic risk factors, including waist circumference
      (WC), blood pressure, cholesterol level, and presence of type 2 diabetes, and
      their relation with death from breast cancer, cardiovascular disease (CVD), and
      other causes among 8641 women with local or regional stage invasive breast
      cancer. Cox proportional hazards models were used to estimate hazard ratios, and
      95% confidence intervals, adjusted for important predictors of survival. RESULTS:
      After a median of 11.3 years, there were 2181 total deaths, 619 (28.4%) of which
      were due to breast cancer. Most participants (55.7%) had at least 2
      cardiometabolic risk factors, and 4.9% had 3 or 4. Having a larger number of risk
      factors was associated with higher risk of CVD and other-cause mortality (P trend
      < .001 for both), but not with breast cancer mortality (P trend = .86). Increased
      WC was associated with a higher risk of CVD (hazard ratio [HR], 1.28; 95%
      confidence interval [CI], 1.05-1.57) and other-cause mortality (HR, 1.32; 95% CI,
      1.16-1.49) and only with a small and nonsignificant higher risk of breast cancer
      mortality (HR, 1.19; 95% CI, 0.93-1.52). The results did not differ in analyses
      stratified by race, hormone receptor status, or after an analysis of cases
      diagnosed within 5 years after baseline. CONCLUSIONS: Among women with early
      stage breast cancer, cardiometabolic risk factors are significantly associated
      with cardiovascular and other-cause mortality, but not breast cancer mortality.
      Cancer 2018;124:1798-807. (c) 2018 American Cancer Society.

PMID- 29338087
TI  - Gabapentin prevents synaptogenesis between sensory and spinal cord neurons
      induced by thrombospondin-4 acting on pre-synaptic Cav alpha2 delta1 subunits and
      involving T-type Ca2+ channels.
AB  - BACKGROUND AND PURPOSE: Nerve injury induces concurrent up-regulation of the
      voltage-gated calcium channel subunit Cav alpha2 delta1 and the extracellular
      matrix protein thrombospondin-4 (TSP4) in dorsal root ganglia and dorsal spinal
      cord, leading to the development of a neuropathic pain state. Interactions of
      these proteins promote aberrant excitatory synaptogenesis that contributes to
      neuropathic pain state development through unknown mechanisms. We investigated
      the contributions of Cav alpha2 delta1 subunits and TSP4 to synaptogenesis, and
      the pathways involved in vitro, and whether treatment with gabapentin could block
      this process and pain development in vivo. EXPERIMENTAL APPROACH: A co-culture
      system of sensory and spinal cord neurons was used to study the contribution from
      each protein to synaptogenesis and the pathway(s) involved. Anti-synaptogenic
      actions of gabapentin were studied in TSP4-injected mice. KEY RESULTS: Only
      presynaptic, but not postsynaptic, Cav alpha2 delta1 subunits interacted with
      TSP4 to initiate excitatory synaptogenesis through a pathway modulated by T-type
      calcium channels. Cav alpha2 delta1 /TSP4 interactions were not required for
      maintenance of already formed synapses. In vivo, early, but not delayed,
      treatment with low-dose gabapentin blocked this pathway and the development of
      the pain state. CONCLUSIONS AND IMPLICATIONS: Cav alpha2 delta1 /TSP4
      interactions were critical for the initiation, but not for the maintenance, of
      abnormal synapse formation between sensory and spinal cord neurons. This process
      was blocked by early, but was not reversed by delayed, treatment with gabapentin.
      Early intervention with gabapentin may prevent the development of injury-induced
      chronic pain, resulting from Cav alpha2 delta1 /TSP4-initiated abnormal synapse
      formation. LINKED ARTICLES: This article is part of a themed section on Recent
      Advances in Targeting Ion Channels to Treat Chronic Pain. To view the other
      articles in this section visit
      http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.12/issuetoc.

PMID- 29338088
TI  - Margins in breast cancer: How much is enough?
AB  - The appropriate negative margin width for women undergoing breast-conserving
      surgery for both ductal carcinoma in situ (DCIS) and invasive carcinoma is
      controversial. This review examines the available data on the margin status for
      invasive breast cancer and DCIS, and highlights the similarities and differences
      in tumor biology and standard treatments that affect the local recurrence (LR)
      risk and, therefore, the optimal surgical margin. Consensus guidelines support a
      negative margin, defined as no ink on tumor, for invasive carcinoma treated with
      breast-conserving therapy. Because of differences in the growth pattern and
      utilization of systemic therapy, a margin of 2 mm has been found to minimize the
      LR risk for women with DCIS undergoing lumpectomy and radiation therapy (RT).
      Wider negative margins do not improve local control for DCIS or invasive
      carcinoma when they are treated with lumpectomy and RT. Re-excision for negative
      margins should be individualized, and the routine practice of performing
      additional surgery to obtain a wider negative margin is not supported by the
      literature. Cancer 2018;124:1335-41. (c) 2018 American Cancer Society.

PMID- 29338089
TI  - Outcomes of patients diagnosed with carcinoma metastatic to the neck from an
      unknown primary source and treated with intensity-modulated radiation therapy.
AB  - BACKGROUND: There are few published studies to guide the treatment of carcinoma
      metastatic to the neck from an unknown primary (CUP). In this regard, the
      objective of the current study was to share the authors' current experience
      treating patients with CUP using intensity-modulated radiation therapy (IMRT),
      which principally targeted both sides of the neck, the nasopharynx, and the
      oropharynx. METHODS: This was a retrospective study in which an institutional
      database search was conducted to identify patients with CUP who received IMRT.
      Data analysis included frequency tabulation, survival analysis, and multivariable
      analysis. RESULTS: Two-hundred sixty patients met inclusion criteria. The most
      common lymph node category was N2b (54%). IMRT volumes included the entire
      pharyngolaryngeal mucosa in 78 patients, the nasopharynx and oropharynx in 167
      patients, and treatment limited to the involved neck in 11 patients. Eighty-four
      patients underwent neck dissections. The 5-year overall survival, regional
      control, and distant metastases-free survival rates were 84%, 91%, and 94%,
      respectively. Over 40% of patients had gastrostomy tubes during therapy, and 7%
      patients were diagnosed with chronic radiation-associated dysphagia. Higher lymph
      node burden was associated with worse disease-related outcomes, and in subgroup
      analysis, patients with human papillomavirus-associated disease had better
      outcomes. No therapeutic modality was statistically associated with either
      disease-related outcomes or toxicity. CONCLUSIONS: Comprehensive IMRT with
      treatment to both sides of the neck and to the oropharyngeal and nasopharyngeal
      mucosa results in high rates of disease control and survival. The investigators
      were unable to demonstrate that treatment intensification with chemotherapy or
      surgery added benefit or excessive toxicity. Cancer 2018;124:1415-27. (c) 2018
      American Cancer Society.

PMID- 29338090
TI  - Influence of provider factors and race on uptake of breast cancer gene expression
      profiling.
AB  - BACKGROUND: Gene expression profiling (GEP) has been rapidly adopted for early
      breast cancer and can aid in chemotherapy decision making. Study results
      regarding racial disparities in testing are conflicting, and may reflect
      different care settings. To the authors' knowledge, data regarding the influence
      of provider factors on testing are scarce. METHODS: The authors used a statewide,
      multipayer, insurance claims database linked to cancer registry records to
      examine the impact of race and provider characteristics on GEP uptake in a cohort
      of patients newly diagnosed with breast cancer between 2005 and 2012. Incidence
      proportion models were used to examine the adjusted likelihood of testing. Models
      were stratified by lymph node status (N0 vs N1). RESULTS: Among 11,958 eligible
      patients, 23% of black and 26% of non-Hispanic white patients received GEP. Among
      patients with N0 disease, black individuals were 16% less likely to receive
      testing after adjustment for clinical factors and the provider's specialty and
      volume of patients with breast cancer (95% confidence interval, 0.77-0.93).
      Adjustment for provider characteristics did not attenuate the effect of race on
      testing. Patients of middle-volume providers were more likely to be tested
      compared with those with either high-volume or low-volume providers, whereas
      patients seeing a medical oncologist were more likely to be tested compared with
      those whose only providers were from surgical specialties. CONCLUSIONS: Provider
      volume and specialty were found to be significant predictors of GEP use, but did
      not explain racial disparities in testing. Further research concerning the key
      contributors to lagging test use among black women is needed to optimize the
      equitable use of GEPs and support personalized treatment decision making for all
      patients. Cancer 2018;124:1743-51. (c) 2018 American Cancer Society.

PMID- 29338091
TI  - Using Difference Scores to Inform Therapy Practice: Differences in Perceptions of
      Attachment Behaviors between Partners in a Clinical Sample.
AB  - Using clinically relevant research methodology, this study focuses on differences
      (cross-partner difference scores) in perceptions of attachment behaviors
      (emotional accessibility, responsiveness, and engagement) between partners in
      couples therapy. In general, findings suggest that higher levels of self
      enhancement attachment behaviors (participant perceives self as demonstrating
      more attachment behaviors than the partner's ratings of the participant) are
      associated with lower relationship satisfaction and greater relationship
      instability. The association between attachment behavior difference scores and
      measures of relationship health is mediated through partner perceived positive
      communication. These results suggest that differences in perceptions between
      partners' level of attachment behaviors are an important clinical construct for
      therapy. As such, clinical recommendations for addressing self-enhancing
      attachment behaviors, and the mediating role of positive communication, are
      discussed with recommendations for researchers.

PMID- 29338092
TI  - Delayed initial radioiodine therapy related to incomplete response in low- to
      intermediate-risk differentiated thyroid cancer.
AB  - OBJECTIVE: Whether the initiating time of radioiodine (RAI) therapy will affect
      the clinical outcome in differentiated thyroid cancer (DTC) remains
      controversial. The objective of this study was to evaluate the impact of RAI
      therapy initiating time on response to initial therapy in low- to intermediate
      risk DTC. METHODS: A total of 235 consecutive patients with low- to intermediate
      risk DTC were retrospectively reviewed. According to the time interval between
      thyroidectomy and RAI therapy, patients were divided into Group 1 (interval < 3
      months, n = 187) and Group 2 (interval >= 3 months, n = 48). Response to RAI
      therapy was evaluated as excellent, indeterminate, biochemical incomplete or
      structural incomplete response (ER, IDR, BIR or SIR) with a median follow-up of
      780 days. The univariate and multivariate analyses were further conducted to
      identify factors associated with incomplete response (IR, including BIR and SIR).
      RESULTS: Response to initial therapy was significantly different between 2 groups
      (P < .05), after excluding the impact of other risk factors (age, gender,
      histological type, status of T and N, RAI dose, thyrotropin, stimulated
      thyroglobulin and follow-up time). A significantly higher IR rate (18.8% vs 4.3%,
      P = .001) and a lower ER proportion (62.5% vs 78.1%, P = .027) were observed in
      Group 2. By univariate analysis, both T status and N status, stimulated
      thyroglobulin and time interval were significant risk factors for IR (P < .05).
      Multivariate analysis demonstrated that the time interval was an independent risk
      factor for IR (P = .008). CONCLUSIONS: Delayed initial RAI therapy (>=3 months
      after thyroidectomy) related to incomplete response in low- to intermediate-risk
      DTC.

PMID- 29338093
TI  - Longitudinal Profiles of Metabolism and Bioenergetics Associated with Innate
      Immune Hormonal Inflammatory Responses and Amino-Acid Kinetics in Severe Sepsis
      and Systemic Inflammatory Response Syndrome in Children.
AB  - BACKGROUND: Experimental data indicate that sepsis influences the mitochondrial
      function and metabolism. We aim to investigate longitudinal bioenergetic,
      metabolic, hormonal, amino-acid, and innate immunity changes in children with
      sepsis. METHODS: Sixty-eight children (sepsis, 18; systemic inflammatory response
      syndrome [SIRS], 23; healthy controls, 27) were enrolled. Plasma amino acids were
      determined by high-performance liquid chromatography (HPLC); flow-cytometry
      expressed as mean fluorescence intensity (MFI) of heat shock protein (HSP) levels
      from monocytes (m) and neutrophils (n); resistin, adiponectin, and extracellular
      (e) HSPs evaluated by ELISA; ATP levels in white blood cells by luciferase
      luminescent assay; lipid peroxidation products (TBARS) by colorimetric test;
      nitrite and nitrate levels by chemiluminescent assay; biliverdin reductase (BVR)
      activity by enzymatic assay; and energy-expenditure (EE) by E-COVX. RESULTS:
      Resistin, eHSP72, eHSP90alpha, and nitrate were longitudinally higher in sepsis
      compared with SIRS (p<0.05); mHSP72, nHSP72, VO2 , VCO2 , EE, and metabolic
      pattern were repressed in sepsis compared with SIRS (p<0.05). Septic patients had
      lower ATP and TBARS compared with controls on day 1, lower ATP compared with SIRS
      on day 3 (p<0.05), but higher levels of BVR activity. Sepsis exhibited higher
      phenylalanine levels on day 1, serine on day 3; lower glutamine concentrations on
      days 3 and 5 (p<0.05). Resistin, inversely related to ATP, was independently
      associated with sepsis, along with mHSP72 and eHSP90alpha (p<0.05); TBARS and VO2
      were independently associated with organ failure (p<0.05)). Septic nonsurvivors
      had malnutrition, persistently repressed metabolism, mHSP72, and induced resistin
      and adiponectin (p<0.05). CONCLUSIONS: A pattern of early longitudinal induction
      of metabolic-hormones and eHSP72/HSP90alpha, repression of bioenergetics and
      innate immunity, hypo-metabolism, and amino-acid kinetics changes discriminate
      sepsis from SIRS; malnutrition, hypo-metabolism, and persistently increased
      resistin and adiponectin are associated with poor outcome.

PMID- 29338094
TI  - Postnatal experiences, knowledge and perceptions of women with gestational
      diabetes.
AB  - AIM: Women with gestational diabetes mellitus (GDM) are at increased risk of Type
      2 diabetes. This study aimed to explore experiences, knowledge and perceptions of
      women with GDM to inform the design of interventions to prevent or delay Type 2
      diabetes. METHODS: Semi-structured interviews were carried out with 16 women with
      GDM who were recruited from a clinic in one Scottish health board. A framework
      approach was used to manage and analyse data according to themes informed by
      psychological theory (self-regulation model and theory of planned behaviour).
      RESULTS: GDM is not seen as an important, or even real diagnosis among some
      women, and this perception may result from the perceived minimal impact of GDM on
      their lives. Some women did experience a bigger emotional and practical impact.
      Knowledge and understanding of Type 2 diabetes was poor in general and many women
      were unconcerned about their future risk. Lower concern appeared to be linked to
      a lower perceived impact of GDM. Lifestyle changes discussed by women mostly
      related to diet and were motivated primarily by concern for their baby's health.
      Many women did not maintain these changes postnatally, reporting significant
      barriers. CONCLUSIONS: This study has suggested potential avenues to be explored
      in terms of content, timing and potential recipients of interventions.
      Educational interventions postnatally could address illness perceptions in women
      with GDM and redress the situation where lack of aftercare downplays its
      seriousness. For lifestyle interventions, the child's health could be used as a
      motivator within the context of later joint or family interventions.

PMID- 29338095
TI  - Patient-controlled tissue collection for genetic testing after early pregnancy
      loss: A pilot study.
AB  - OBJECTIVE: To determine how frequently and effectively products of conception can
      be obtained among women pursuing medical management of early pregnancy loss.
      METHODS: This pilot study was conducted to assess products of conception recovery
      outcomes for participants opting for medical management compared with women
      opting for surgical aspiration A tissue-collection kit was provided to women
      opting for medical management. Outcome measures included successful collection of
      products of conception, quantity and integrity of DNA, and participant
      satisfaction with the process. RESULTS: Tissue was collected from 19 of 22
      participants in the medical management group (84%) and 39 participants (100%) in
      the surgical management group (P = .02). DNA yield and integrity were similar
      among both groups (P = .03 and P = .003, respectively). Participants in the
      medical group reported a high comfort level with the kit and the process of
      tissue collection. CONCLUSIONS: Medical management of a missed abortion followed
      by patient-controlled collection of products of conception for subsequent
      cytogenetic analysis is well tolerated and highly effective. This methodology may
      reduce the need for surgical management, empower women to have more agency in
      their medical decisions, and increase access to genetic testing.

PMID- 29338096
TI  - Controlling Selectivity in Aliphatic C-H Oxidation through Supramolecular
      Recognition.
AB  - Aliphatic C-H oxidation is the most straightforward approach to functionalize
      hydrocarbon skeletons. The main challenge of this reaction is the control of site
      selectivity, given the multiple C-H bonds present in any organic molecule.
      Natural enzymes elegantly solve this problem through the interplay of different
      interactions that geometrically orient the substrate to expose a single C-H bond
      to the active unit, thus overriding intrinsic reactivity patterns. A combination
      of molecular catalysts and supramolecular receptors can be a promising way to
      replicate such control. This strategy indeed unlocks hydroxylation of C-H bonds
      that are not accessible with conventional methodologies, in which the selectivity
      is dictated by the geometry of the substrate-receptor adduct. Herein, we review
      the reports of recognition-driven C-H oxidation reactions and highlight the key
      design principles that inspired these works.

PMID- 29338097
TI  - Synthesis of Multifunctional Spirocyclic Azetidines and Their Application in Drug
      Discovery.
AB  - The synthesis of multifunctional spirocycles was achieved from common cyclic
      carboxylic acids (cyclobutane carboxylate, cyclopentane carboxylate, l-proline,
      etc.). The whole sequence included only two chemical steps-synthesis of
      azetidinones, and reduction into azetidines. The obtained spirocyclic amino acids
      were incorporated into a structure of the known anesthetic drug Bupivacaine. The
      obtained analogues were more active and less toxic than the original drug. We
      believe that this discovery will lead to a wide use of spirocyclic building
      blocks in drug discovery in the near future.

PMID- 29338099
TI  - Establishing the Critical Role of Oriented Aggregation in Molecular Solid State
      Fluorescence Enhancement.
AB  - The general occurrence of fluorescence emission quenching in molecular aggregates
      is circumvented in select classes of molecules. This has largely been attributed
      to the rigidification of the molecule and its environment, which hinders non
      radiative excited state energy loss through structural relaxation; since such an
      effect should in principle apply to most aggregates and crystals, there must
      clearly be other critical factors that make the select molecules exceptional.
      Discovery of three crystalline structures of a new push-pull molecule in its
      enantiomorphic and racemic forms, exhibiting not only very high, but distinctly
      different solid state fluorescence enhancements, has now allowed a systematic
      investigation of the role of intramolecular and intermolecular excited state
      energy loss pathways. Crystallographic, spectroscopic and computational
      investigations provide a detailed appraisal of the assembly patterns in the
      crystals, and rigorous establishment of an inverse correlation between
      intermolecular energy transfer and solid state fluorescence. The study provides a
      clear visualization of the critical role of oriented molecular aggregation in
      solid state fluorescence efficiency enhancement.

PMID- 29338098
TI  - Increase in motility and invasiveness of MCF7 cancer cells induced by nicotine is
      abolished by melatonin through inhibition of ERK phosphorylation.
AB  - Through activation of the ERK pathway, nicotine, in both normal MCF-10A and low
      malignant breast cancer cells (MCF7), promotes increased motility and
      invasiveness. Melatonin antagonizes both these effects by inhibiting almost
      completely ERK phosphorylation. As melatonin has no effect on nonstimulated
      cells, it is likely that melatonin can counteract ERK activation only downstream
      of nicotine-induced activation. This finding suggests that melatonin hampers ERK
      phosphorylation presumably by targeting a still unknown intermediate factor that
      connects nicotine stimulation to ERK phosphorylation. Furthermore, downstream of
      ERK activation, melatonin significantly reduces fascin and calpain activation
      while restoring normal vinculin levels. Melatonin also counteracts nicotine
      effects by reshaping the overall cytoskeleton architecture and abolishing
      invasive membrane protrusion. In addition, melatonin decreases nicotine-dependent
      ROCK1/ROCK2 activation, thus further inhibiting cell contractility and motility.
      Melatonin actions are most likely attributable to ERK inhibition, although
      melatonin could display other ERK-independent effects, namely through a direct
      modulation of additional molecular and structural factors, including coronin,
      cofilin, and cytoskeleton components.

PMID- 29338100
TI  - Fixing the Conformation of Calix[4]arenes: When Are Three Carbons Not Enough?
AB  - Calix[4]arenes are unique macrocycles that through judicious functionalisation at
      the lower rim can be either fixed in one of four conformations or remain
      conformationally flexible. Introduction of propynyl or propenyl groups
      unexpectedly provides a new possibility; a unidirectional conformational switch,
      with the 1,3-alternate and 1,2-alternate conformers switching to the partial cone
      conformation, whilst the cone conformation is unchanged, under standard
      experimental conditions. Using 1 H NMR kinetic studies, rates of switching have
      been shown to be dependent on the starting conformation, upper-rim substituent,
      where reduction in bulk enables faster switching, solvent and temperature with
      1,2-alternate conformations switching fastest. Ab initio calculations (DFT)
      confirmed the relative stabilities of the conformations and point towards the
      partial cone conformer being the most stable of the four. The potential impact on
      synthesis through the "click" reaction has been investigated and found not to be
      significant.

PMID- 29338101
TI  - Mechanochromic Polymers That Turn Green Upon the Dissociation of
      Diarylbibenzothiophenonyl: The Missing Piece toward Rainbow Mechanochromism.
AB  - Mechanochromic polymers, that is, polymers sensitive to mechanical impact,
      promise great potential for applications in damage sensors. In particular,
      radical-type mechanochromic polymers, which produce colored radical species in
      response to mechanical stress, may enable not only the visualization of
      mechanical stress, but also its quantitative evaluation by electron paramagnetic
      resonance analysis. Herein, a radical-type mechanochromic polymer that exhibits a
      color change from white to green upon dissociation of a diarylbibenzothiophenonyl
      moiety at the mid-point of a polystyrene chain is presented, and its
      mechanochromic behavior is examined. Mechanochromic materials that show a variety
      of colors ("rainbow colors") in response to mechanical stress were prepared by
      simply mixing radical-type mechanochromic polymers of primary colors.

PMID- 29338102
TI  - Circulating Serum 25-Hydroxyvitamin D Levels and Bone Mineral Density: Mendelian
      Randomization Study.
AB  - There is considerable discussion of the importance for increased serum 25
      hydroxyvitamin D (S-25OHD) concentration associated with adequacy for bone
      health. Accordingly, whether long-term high S-25OHD concentration in general
      positively affects bone mineral density (BMD) is uncertain. We used a Mendelian
      randomization design to determine the association between genetically increased S
      25OHD concentrations and BMD. Five single-nucleotide polymorphisms (SNPs) in or
      near genes encoding enzymes and carrier proteins involved in vitamin D synthesis
      or metabolism were used as instrumental variables to genetically predict 1
      standard deviation increase in S-25OHD concentration. Summary statistics data for
      the associations of the S-25OHD-associated SNPs with dual-energy X-ray
      absorptiometry (DXA)-derived femoral neck and lumbar spine BMD were obtained from
      the Genetic Factors for Osteoporosis (GEFOS) Consortium (32,965 individuals) and
      ultrasound-derived heel estimated BMD from the UK Biobank (142,487 individuals).
      None of the SNPs were associated with BMD at Bonferroni-corrected significance
      level, but there was a suggestive association between rs6013897 near CYP24A1 and
      femoral neck BMD (p = 0.01). In Mendelian randomization analysis, genetically
      predicted 1 standard deviation increment of S-25OHD was not associated with
      higher femoral neck BMD (SD change in BMD 0.02; 95% confidence interval [CI] 
      0.03 to 0.07; p = 0.37), lumbar spine BMD (SD change in BMD 0.02; 95% CI -0.04 to
      0.08; p = 0.49), or estimated BMD (g/cm2 change in BMD -0.03; 95% CI -0.05 to 
      0.01; p = 0.02). This study does not support a causal association between long
      term elevated S-25OHD concentrations and higher BMD in generally healthy
      populations. These results suggest that more emphasis should be placed on the
      development of evidence-based cut-off points for vitamin D inadequacy rather than
      a general recommendation to increase S-25OHD. (c) 2018 American Society for Bone
      and Mineral Research.

PMID- 29338104
TI  - Organotin Dyes Bearing Anionic Boron Clusters as Cell-Staining Fluorescent
      Probes.
AB  - Within the cell nucleus, in the nucleoli, ribosomal RNAs are synthesized and
      participate in several biological processes. To better understand nucleoli
      related processes, their visualization is often required, for which specific
      markers are needed. Herein, we report the design of novel fluorescent organotin
      compounds derived from 4-hydroxy-N'-((2-hydroxynaphthalen-1
      yl)methylene)benzohydrazide and their cytoplasm and nucleoli staining of B16F10
      cells in vitro. Tin compounds bearing an aliphatic carbon chain (-C12 H25 ) and
      an electron-donating group (-OH) were prepared, and the latter could be
      derivatized to bear the boron cluster anions [B12 H12 ]2- and [3,3'-Co(1,2-C2 B9
      H11 )2 ]- (COSAN). All of the conjugates have been fully characterized and their
      luminescence properties have been assessed. In general, they show good quantum
      yields in solution (24-49 %), those for the COSAN derivatives being lower.
      Remarkably, the linking of [B12 H12 ]2- and COSAN to the complexes made them more
      soluble, without being detrimental to their luminescence properties. Living
      B16F10 cells were treated with all of the compounds to determine their
      fluorescence staining properties; the compounds bearing the aliphatic chain
      showed a reduced staining capacity due to the formation of aggregates. Notably,
      the complexes bearing different boron clusters showed different staining effects;
      those bearing [B12 H12 ]2- showed extraordinary staining of the nucleoli and
      cytoplasm, whereas those bearing COSAN were only detected in the cytoplasm. The
      remarkable fluorescence staining properties shown by these organotin compounds
      make them excellent candidates for fluorescence bioimaging in vitro.

PMID- 29338105
TI  - Multiple sclerosis: long-term outcomes in ethnic minorities. Analysis of a UK
      population-based registry.
AB  - BACKGROUND AND PURPOSE: Multiple sclerosis (MS) is most frequent in Caucasian
      populations. However, studies of MS in other ethnic groups may offer unique
      insights into genetic and environmental influences on the disease, and data on
      long-term outcomes in these patients is limited. In this work clinical features
      and time to disability milestones were investigated in ethnic minority (EM)
      patients with MS in a UK population and comparisons were made to a Caucasian
      cohort from the same region. METHODS: In all, 1949 MS patients (1866 Caucasian,
      83 EM) were identified from a regional disease registry. Cox proportional hazards
      regression was used to analyse the time to Expanded Disability Status Scale
      (EDSS) 3.0, 4.0 and 6.0. RESULTS: Ethnic minority patients were younger at
      disease onset (28.6 years vs. 32.8 years, P = 0.001), and primary progressive MS
      was less common (EM 4.8%, Caucasian 11.6%, P = 0.03). After correction for
      clinical variables, ethnicity was associated with time to EDSS 3.0 [EM: hazard
      ratio (HR) 1.75, P < 0.0001] and 4.0 (HR 1.46, P = 0.03), but not 6.0 (HR 1.5, P
      = 0.05). CONCLUSIONS: Ethnic minority patients reach early levels of fixed
      disability more rapidly than Caucasian patients, but this effect diminishes at
      later stages of the disease. This has implications for clinical management of
      these patients.

PMID- 29338106
TI  - Morning hypertension in Asian populations.

PMID- 29338103
TI  - Interrogating Protein Phosphatases with Chemical Activity Probes.
AB  - Protein phosphatases, while long overlooked, have recently become appreciated as
      drivers of both normal- and disease-associated signaling events. As a result, the
      spotlight is now turning torwards this enzyme family and efforts geared towards
      the development of modern chemical tools for studying these enzymes are well
      underway. This Minireview focuses on the evolution of chemical activity probes,
      both optical and covalent, for the study of protein phosphatases. Small-molecule
      probes, global monitoring of phosphatase activity through the use of covalent
      modifiers, and targeted fluorescence-based activity probes are discussed. We
      conclude with an overview of open questions in the field and highlight the
      potential impact of chemical tools for studying protein phosphatases.

PMID- 29338107
TI  - How often is the diagnosis of the permanent vegetative state incorrect? A review
      of the evidence.
AB  - Some research suggests that 40% of people in the vegetative state are
      misdiagnosed. This review investigates the frequency, nature and causes of
      reported misdiagnosis of patients in the vegetative state, focusing on the nature
      of the error. It is a systematic review of all relevant literature, using
      references from key papers identified. The data are summarized in tables. Five
      clinical studies of the rate of misdiagnosis in practice were identified,
      encompassing 236 patients in the vegetative state of whom 80 (34%) were
      reclassified as having some awareness, often minimal. The studies often included
      patients in the recovery phase after acute injury, and were poorly reported. Five
      systematic reviews of signs and technologically based neurophysiological tests
      were identified, and they showed that most studies were small, lacked accurate or
      important details, and were subject to bias. Studies were not replicated. Many
      signs and tests did not differ between people in the vegetative state and in the
      minimally conscious state, and those that did were unable to diagnose an
      individual patient. The few single case reports suggest that failure to ensure an
      accurate diagnosis of the underlying neurological damage and dysfunction could,
      rarely, lead to significant misdiagnosis usually in patients who had brain-stem
      damage with little thalamic or cortical damage. Significant misdiagnosis of
      awareness, with an apparently 'vegetative' patient having good awareness, is
      rare. Careful neurological assessment of the cause and routine measurement of
      awareness using the Coma Recovery Scale - Revised should further reduce mistakes.

PMID- 29338108
TI  - The timing of liver resection in patients with colorectal cancer and synchronous
      liver metastases: a population-based study of current practice and survival.
AB  - AIM: There is uncertainty regarding the optimal sequence of surgery for patients
      with colorectal cancer (CRC) and synchronous liver metastases. This study was
      designed to describe temporal trends and inter-hospital variation in surgical
      strategy, and to compare long-term survival in a propensity score-matched
      analysis. METHOD: The National Bowel Cancer Audit dataset was used to identify
      patients diagnosed with primary CRC between 1 January 2010 and 31 December 2015
      who underwent CRC resection in the English National Health Service. Hospital
      Episode Statistics data were used to identify those with synchronous liver
      limited metastases who underwent liver resection. Survival outcomes of propensity
      score-matched groups were compared. RESULTS: Of 1830 patients, 270 (14.8%)
      underwent a liver-first approach, 259 (14.2%) a simultaneous approach and 1301
      (71.1%) a bowel-first approach. The proportion of patients undergoing either a
      liver-first or simultaneous approach increased over the study period from 26.8%
      in 2010 to 35.6% in 2015 (P < 0.001). There was wide variation in surgical
      approach according to hospital trust of diagnosis. There was no evidence of a
      difference in 4-year survival between the propensity score-matched cohorts
      according to surgical strategy: bowel first vs simultaneous [hazard ratio (HR)
      0.92 (95% CI: 0.80-1.06)] or bowel first vs liver first [HR 0.99 (95% CI: 0.82
      1.19)]. CONCLUSION: There is evidence of wide variation in surgical strategy in
      dealing with CRC and synchronous liver metastases. In selected patients, the
      simultaneous and liver-first strategies have comparable long-term survival to the
      bowel-first approach.

PMID- 29338110
TI  - Is it time to utilize measurement of arterial stiffness to identify and reduce
      the risk of cognitive impairment?

PMID- 29338109
TI  - Fused-Ring Formation by an Intramolecular "Cut-and-Sew" Reaction between
      Cyclobutanones and Alkynes.
AB  - The development of a catalytic intramolecular "cut-and-sew" transformation
      between cyclobutanones and alkynes to construct cyclohexenone-fused rings is
      described herein. The challenge arises from the need for selective coupling at
      the more sterically hindered proximal position, and can be addressed by using an
      electron-rich, but less bulky, phosphine ligand. The control experiment and 13 C
      labelling study suggest that the reaction may start with cleavage of the less
      hindered distal C-C bond of cyclobutanones, followed by decarbonylation and CO
      reinsertion to enable Rh insertion at the more hindered proximal position.

PMID- 29338111
TI  - The exaggerated blood pressure response to exercise in the sub-acute phase after
      stroke is not affected by aerobic exercise.
AB  - The prevalence of an exaggerated exercise blood pressure (BP) response is unknown
      in patients with subacute stroke, and it is not known whether an aerobic exercise
      program modulates this response. The authors randomized 53 patients (27 women)
      with subacute stroke to 12 weeks of twice-weekly aerobic exercise (n = 29) or to
      usual care without scheduled physical exercise (n = 24). At baseline, 66% of the
      patients exhibited an exaggerated exercise BP response (peak systolic BP >=210 mm
      Hg in men and >=190 mm Hg in women) during a symptom-limited ergometer exercise
      test. At follow-up, patients who had been randomized to the exercise program
      achieved higher peak work rate, but peak systolic BP remained unaltered. Among
      patients with a recent stroke, it was common to have an exaggerated systolic BP
      response during exercise. This response was not altered by participation in a 12
      week program of aerobic exercise.

PMID- 29338112
TI  - Benefits and pitfalls of sacubitril/valsartan treatment in patients with
      hypertension.

PMID- 29338113
TI  - Efficacy and safety of sacubitril/valsartan in patients with essential
      hypertension uncontrolled by olmesartan: A randomized, double-blind, 8-week
      study.
AB  - A majority of patients with hypertension fail to achieve blood pressure (BP)
      control despite treatment with commonly prescribed drugs. This randomized, double
      blind phase III trial assessed the superiority of sacubitril/valsartan 200 mg
      (97/103 mg) to continued olmesartan 20 mg in reducing ambulatory systolic BP
      after 8-week treatment in patients with mild to moderate essential hypertension
      uncontrolled with olmesartan 20 mg alone. A total of 376 patients were randomized
      to receive either sacubitril/valsartan (n = 188) or olmesartan (n = 188).
      Superior reductions in 24-hour mean ambulatory systolic BP were observed in the
      sacubitril/valsartan group vs the olmesartan group (-4.3 mm Hg vs -1.1 mm Hg, P <
      .001). Reductions in 24-hour mean ambulatory diastolic BP and pulse pressure and
      office systolic BP and diastolic BP were significantly greater with
      sacubitril/valsartan vs olmesartan (P < .014). A greater proportion of patients
      achieved BP control with sacubitril/valsartan vs olmesartan. The overall
      incidence of adverse events was comparable between the groups. Compared with
      continued olmesartan, sacubitril/valsartan was more effective and generally safe
      in patients with hypertension uncontrolled with olmesartan 20 mg.

PMID- 29338114
TI  - Divergent Pathways Involving 1,3-Dipolar Addition and N-N Bond Splitting of an
      Organic Azide across a Zirconium Methylidene.
AB  - The zirconium methylidene (PNP)Zr=CH2 (OAr) (1) reacts with N3 Ad to give two
      products (PNP)Zr=NAd(OAr) (2) and (PNP)Zr(eta2 -N=NAd)(N=CH2 )(OAr) (3), both
      resulting from a common cycloaddition intermediate (PNP)Zr(CH2 N3 Ad)(OAr) (A).
      Using a series of control experiments in combination with DFT calculations, it
      was found that 2 results from a nitrene by a carbene metathesis reaction in which
      N2 acts as a delivery vehicle and forms N2 CH2 as a side product. In the case of
      3, N-N bond splitting of the azide at the alpha-position allowed the isolation of
      a rare example of a parent ketimide complex of zirconium. Isotopic labeling
      studies and solid-state X-ray analysis are presented for 2 and 3, in addition to
      an independent synthesis for the former.

PMID- 29338115
TI  - Statin use and vitreoretinal surgery: Findings from a Finnish population-based
      cohort study.
AB  - PURPOSE: Vitreoretinal (VR) surgery is the third most common intraocular surgery
      after refractive and cataract surgery. The impact of statin therapy on VR surgery
      outcomes remains unclear, despite a potentially beneficial effect. We explored
      the association of preoperative statin therapy and the need for revitrectomy
      after primary vitrectomy. METHODS: Our historical, population-based, register
      based, VR surgery cohort consisted of 5709 patients operated in a tertiary,
      academic referral hospital in Finland, during 2008-2014, covering 6.5 years.
      Subgroup analysis was performed as follows: eyes operated due to (i)
      rhegmatogenous retinal detachment (RRD), (ii) VR interface diseases (macular
      pucker/hole), (iii) diabetic maculopathy or proliferative retinopathy, (iv)
      vitreous haemorrhage, (v) lens subluxation, (vi) vitreous opacities or (vii)
      other VR indication. The primary end-point event was revitrectomy during a
      postoperative follow-up period of 1 year due to retinal redetachment, vitreous
      rehaemorrhage, postoperative endophthalmitis, recurrent pucker or unclosed
      macular hole. RESULTS: Rhegmatogenous retinal detachment (RRD) was the second
      most frequent indication of VR surgery, including 1916 patients, with 305 re
      operations with rate 0.20 (95% CI 0.18-0.23) per person-year. Statin treatment in
      time of operation was associated with lower risk of re-operation according to
      relative scale (incidence rate ratio 0.72, 95% CI 0.53-0.97), but not in absolute
      scale (incidence rate difference -0.58, 95% CI -4.30 to 3.15 for 100 person
      years). No association with statin therapy and vitrectomy outcome was observed in
      the other VR subgroups. CONCLUSION: Use of statin treatment was associated with a
      28% lower risk of revitrectomy in patients operated due to RRD. Further
      randomized clinical trials are highly warranted.

PMID- 29338116
TI  - Carbon Dioxide Promotes Dehydrogenation in the Equimolar C2 H2 -CO2 Reaction to
      Synthesize Carbon Nanotubes.
AB  - The equimolar C2 H2 -CO2 reaction has shown promise for carbon nanotube (CNT)
      production at low temperatures and on diverse functional substrate materials;
      however, the electron-pushing mechanism of this reaction is not well
      demonstrated. Here, the role of CO2 is explored experimentally and theoretically.
      In particular, 13 C labeling of CO2 demonstrates that CO2 is not an important C
      source in CNT growth by thermal catalytic chemical vapor deposition. Consistent
      with this experimental finding, the adsorption behaviors of C2 H2 and CO2 on a
      graphene-like lattice via density functional theory calculations reveal that the
      binding energies of C2 H2 are markedly higher than that of CO2 , suggesting the
      former is more likely to incorporate into CNT structure. Further, H-abstraction
      by CO2 from the active CNT growth edge would be favored, ultimately forming CO
      and H2 O. These results support that the commonly observed, promoting role of CO2
      in CNT growth is due to a CO2 -assisted dehydrogenation mechanism.

PMID- 29338117
TI  - Nestin expression in primary and metastatic uveal melanoma - possible biomarker
      for high-risk uveal melanoma.
AB  - PURPOSE: Nestin, a member of the intermediate filament protein family, has been
      described as a putative cancer stem cell marker (CSC) in uveal melanoma and poor
      prognostic factor in a variety of tumours, including cutaneous melanoma. In this
      study, we examined the expression of nestin in primary (PUM) and metastatic uveal
      melanoma (MUM) samples, and correlated the findings with histological, clinical
      and survival data. METHODS: Nestin expression was assessed by
      immunohistochemistry in 141 PUM and 26 MUM samples; 11 PUM cases were matched
      with their corresponding metastases. The percentage of tumour cells expressing
      nestin was scored by three independent observers. Statistical analysis of all
      data was performed with SPSS. RESULTS: Nestin expression was identified in both
      the cytoplasm and membrane of UM cells. Increased expression of nestin in PUM
      samples was associated with known poor prognostic parameters, including
      epithelioid cell morphology (p < 0.001), closed loops (p = 0.001), higher mitotic
      count (p < 0.001), monosomy 3 (p = 0.007) and chromosome 8q gain (p < 0.001).
      Primary uveal melanoma (PUM) with nestin expression levels above a cut-off value
      of 10% [as determined by receiver operating characteristic (ROC) analysis] was
      associated with a significantly reduced survival time (Log-rank, p = 0.002). In
      MUM, a higher percentage of nestin-positive tumour cells combined with poor
      prognostic markers in the PUM led to a shorter survival time following the
      development of metastases. CONCLUSION: In conclusion, increased nestin expression
      in PUM is a predictor of a tumour phenotype associated with metastatic
      progression and reduced survival time at onset of metastasis.

PMID- 29338118
TI  - Impact of quality of research on patient outcomes in the Institute of Medicine
      2013 report on dietary sodium.
AB  - The 2013 Institute of Medicine report entitled "Sodium Intake in Populations:
      Assessment of Evidence" found inconsistent evidence of health benefit with
      dietary sodium intake <2300 mg/d. Different studies reported benefit and harm of
      population dietary intake <2300 mg/d. The Institute of Medicine committee,
      however, did not assess whether the methodology used in each of the studies was
      appropriate to examine dietary sodium and health outcomes. This review
      investigates the association of methodological rigor and outcomes of studies in
      the Institute of Medicine report. For the 13 studies that met all methodological
      criteria, nine found a detrimental impact of high sodium consumption on health,
      one found a health benefit, and in three the effect was unclear (P = .068). For
      the 22 studies that failed to meet all criteria, 11 showed a detrimental impact,
      four a health benefit, and seven had unclear effects from increasing dietary
      sodium (P = .42).

PMID- 29338119
TI  - Management of morning hypertension: a consensus statement of an Asian expert
      panel.
AB  - Morning blood pressure (BP) surge is an important aspect of hypertension
      research. Morning BP monitoring could be a clinically relevant concept in the
      therapeutic management of hypertension and in the prevention of cardiovascular
      complications by defining and treating morning hypertension. Because
      antihypertensive medication is often taken in the morning, uncontrolled morning
      BP during the trough effect hours could be a hallmark of inadequate choice of
      antihypertensive regimen, such as the use of short- or intermediate-acting drugs,
      underdosing of drugs, or no use or underuse of combination therapy. To improve
      the management of hypertension in general and morning hypertension in particular,
      long-acting antihypertensive drugs should be used in appropriate, often full
      dosages and in proper combinations. The clinical usefulness of antihypertensive
      drugs with specific mechanisms for morning BP or split or timed dosing of long
      acting drugs in controlling morning BP remains under investigation.

PMID- 29338120
TI  - The association between different features of sleep-disordered breathing and
      blood pressure: A cross-sectional study.
AB  - Sleep disordered breathing (SDB) is highly prevalent in patients with high blood
      pressure (BP). Severity of SDB can be evaluated by the number of apneas and
      hypopneas per hour (AHI) or by measures of hypoxia. The objective of this study
      was to assess the association between different measures of SDB and BP. In 134
      consecutive patients, polygraphy was performed to determine the AHI. Pulse
      oximetry was used to determine hypoxemic burden (time below 90% oxygen saturation
      [T90] and hypoxia load [HL], representing the integrated area above the curve of
      desaturation). AHI did not correlate with systolic and diastolic BP or pulse
      pressure. In contrast, HL correlated with pulse pressure during the day (P = .01)
      and night (P = .0034) before and after adjustment for body mass index. The
      correlation between systolic BP and HL at night disappeared following adjustment
      for body mass index. This study generates the hypothesis that nocturnal hypoxemic
      burden may represent a suitable marker of BP pattern and a potential treatment
      target in hypertensive patients.

PMID- 29338121
TI  - Does Confucianism allow for body donation?
AB  - Confucianism has been widely perceived as a major moral and cultural obstacle to
      the donation of bodies for anatomical purposes. The rationale for this is the
      Confucian stress on xiao (filial piety), whereby individuals' bodies are to be
      intact at death. In the view of many, the result is a prohibition on the donation
      of bodies to anatomy departments for the purpose of dissection. The role of
      dissection throughout the development of anatomy within a Confucian context is
      traced, and in contemporary China the establishment of donation programs and the
      appearance of memorial monuments is noted. In reassessing Confucian attitudes,
      the stress laid on a particular interpretation of filial piety is questioned, and
      an attempt is made to balance this with the Confucian emphasis on a moral duty to
      those outside one's immediate family. The authors argue that the fundamental
      Confucian norm ren (humaneness or benevolence) allows for body donation as people
      have a moral duty to help others. Moreover, the other central Confucian value, li
      (rites), offers important insights on how body donation should be performed as a
      communal activity, particularly the necessity of developing ethically and
      culturally appropriate rituals for body donation. In seeking to learn from this
      from a Western perspective, it is contended that in all societies the voluntary
      donation of bodies is a deeply human activity that is to reflect the
      characteristics of the community within which it takes place. This is in large
      part because it has educational and personal repercussions for students. Anat Sci
      Educ 11: 525-531. (c) 2018 American Association of Anatomists.

PMID- 29338122
TI  - NO, CO and H2 S: What about gasotransmitters in fish and amphibian heart?
AB  - The gasotransmitters nitric oxide (NO), carbon monoxide (CO), and hydrogen
      sulphide (H2 S), long considered only toxicant, are produced in vivo during the
      catabolism of common biological molecules and are crucial for a large variety of
      physiological processes. Mounting evidence is emerging that in poikilotherm
      vertebrates, as in mammals, they modulate the basal performance of the heart and
      the response to stress challenges. In this review, we will focus on teleost fish
      and amphibians to highlight the evolutionary importance in vertebrates of the
      cardiac control elicited by NO, CO and H2 S, and the conservation of the
      intracellular cascades they activate. Although many gaps are still present due to
      discontinuous information, we will use examples obtained by studies from our and
      other laboratories to illustrate the complexity of the mechanisms that, by
      involving gasotransmitters, allow beat-to-beat, short-, medium- and long-term
      cardiac homoeostasis. By presenting the latest data, we will also provide a
      framework in which the peculiar morpho-functional arrangement of the teleost and
      amphibian heart can be considered as a reference tool to decipher cardiac
      regulatory networks which are difficult to explore using more conventional
      vertebrates, such as mammals.

PMID- 29338123
TI  - Choroidal thickness and myopia in relation to physical activity - the CHAMPS Eye
      Study.
AB  - PURPOSE: To describe the relationship between choroidal thickness (CT) and myopia
      in relation to physical activity (PA) in a population-based child cohort.
      METHODS: In a prospective study of 307 children from the CHAMPS Study Denmark, we
      used objective data from GT3X accelerometer worn at four periods between 2009 and
      2015 to determine the amount and intensity of PA. Intensity was estimated as
      counts/minutes, and cut-off points were defined at four intensity levels. Eye
      examinations were performed in 2015 and included autorefraction in cycloplegia,
      axial length (AL) by biometric and fovea-centred enhanced depth imaging optical
      coherence tomography. By a semi-automated method, we measured the CT at 17
      targets per eye representing anatomically different locations (subfoveal, 1 and 3
      millimetre in each direction of fovea). RESULTS: Mean age at the eye examination
      was 15.4 +/- 0.7 years. The mean AL was 23.5 +/- 0.9 mm, and the mean subfoveal
      CT was 369 +/- 87 MUm. Choroidal thickness (CT) was 331 +/- 68 MUm for the
      overall macula, 355 +/- 78 MUm for the 1-mm zone and 304 +/- 60 MUm for the 3-mm
      zone. All CT measurements were thinner in myopic eyes (p < 0.0001) and in boys (p
      < 0.05). We found no association between total PA and the CT by either mixed
      model analysis (p = 0.074) or linear regression by any intensity levels (p =
      0.22, p = 0.15 and p = 0.43). CONCLUSION: Among adolescents aged 14-17 years,
      there was no association between objective PA exposures and the CT, AL or
      refractive error.

PMID- 29338125
TI  - Innovative case-writing software can engage millennials in learning pathology
      topics.

PMID- 29338124
TI  - Conservative therapy for chalazia: is it really effective?
AB  - PURPOSE: To assess the within-treatment efficacy of hot compresses (HC), HC plus
      tobramycin (Tobrex) and HC plus tobramycin/dexamethasone (Tobradex) for chalazia
      treatment. METHODS: Design: Multicentre, randomized clinical trial
      (ClinicalTrials.gov identifier, NCT01230593). SETTING: Two clinical sites in New
      York and two clinical sites in Ontario. STUDY POPULATION: A total of 149 patients
      with one or more chalazia on separate eyelids randomly assigned to receive HC (n
      = 50), HC plus tobramycin (n = 50) or HC plus tobramycin/dexamethasone (n = 49).
      INTERVENTION: 4-6 weeks of assigned treatment. Patients were measured for
      chalazion horizontal width and surveyed for pain and treatment satisfaction
      levels. MAIN OUTCOME MEASURES: Primary outcome was complete resolution (100% size
      reduction). Secondary outcomes were size change in millimetres and patient
      reported pre- and post-treatment pain and satisfaction levels. RESULTS: In the
      intention-to-treat (ITT) population, complete resolution occurred in 36 (18%)
      lesions total, 13 (21%) treated with HC, 12 (16%) with HC plus tobramycin and 11
      (18%) with HC plus tobramycin/dexamethasone, with no significant difference
      between them (p = .78). Individually by paired t-test, there were statistically
      significant post-treatment mean size differences: HC 1.20 mm (p < 0.001), HC plus
      tobramycin 1.69 mm (p < .001) and HC plus tobramycin/dexamethasone 1.54 mm (p <
      0.001), but no significant difference between them (p = .61). Lesions that
      completely resolved had a statistically significant lower pretreatment duration
      (1.5 months) compared to lesions that did not completely resolve (2.2 months) (p
      = .04). CONCLUSION: Hot compresses (HC) alone or in combination with tobramycin
      or tobramycin/dexamethasone drops and ointment are all effective first-line
      treatment options for chalazia. However, physicians may consider moving directly
      to the use of more invasive therapies, such as incision and curettage or steroid
      injections, for chalazia that have been present for more than 2 months, as older
      lesions are less likely to resolve with conservative therapies alone.

PMID- 29338126
TI  - Physical exercise and glaucoma: a review on the roles of physical exercise on
      intraocular pressure control, ocular blood flow regulation, neuroprotection and
      glaucoma-related mental health.
AB  - The benefits of physical exercise on health and well-being have been studied in a
      wide range of systemic and ocular diseases, including glaucoma, a progressive
      optic neuropathy characterized by accelerated apoptosis of retinal ganglion cells
      (RGCs). Elevated intraocular pressure (IOP) and insufficient ocular perfusion
      have been postulated to be the two main theories in glaucoma development and
      progression. The effects of exercise in these two aspects have been demonstrated
      by numerous researches. A review in 2009 focusing on these two theories concluded
      that exercise results in transient IOP reduction but an inconsistent elevation in
      ocular perfusion. However, the majority of the studies had been conducted in
      healthy subjects. Over the past decade, technological advancement has brought
      forth new and more detailed evidence regarding the effects of exercise. Moreover,
      the neuroprotective effect of exercise by upregulation of neurotrophin and
      enhancement of mitochondrial function has been a focus of interest. Apart from
      visual impairment, the mental health issues in patients with glaucoma, which
      include anxiety and depression, should also be addressed. In this review, we
      mainly focus on publications from the recent years, so as to provide a
      comprehensive review on the impact of physical exercise on IOP, ocular perfusion,
      neuroprotection and mental health in patients with glaucoma.

PMID- 29338127
TI  - Establishment of practical recellularized liver graft for blood perfusion using
      primary rat hepatocytes and liver sinusoidal endothelial cells.
AB  - Tissue decellularization produces a three-dimensional scaffold that can be used
      to fabricate functional liver grafts following recellularization. Inappropriate
      cell distribution and clotting during blood perfusion hinder the practical use of
      recellularized livers. Here we aimed to establish a seeding method for the
      optimal distribution of parenchymal and endothelial cells, and to evaluate the
      effect of liver sinusoidal endothelial cells (LSECs) in the decellularized liver.
      Primary rat hepatocytes and LSECs were seeded into decellularized whole-liver
      scaffolds via the biliary duct and portal vein, respectively. Biliary duct
      seeding provided appropriate hepatocyte distribution into the parenchymal space,
      and portal vein-seeded LSECs simultaneously lined the portal lumen, thereby
      maintaining function and morphology. Hepatocytes co-seeded with LSECs retained
      their function compared with those seeded alone. Platelet deposition was
      significantly decreased and hepatocyte viability was maintained in the co-seeded
      group after extracorporeal blood perfusion. In conclusion, our seeding method
      provided optimal cell distribution into the parenchyma and vasculature according
      to the three-dimensional structure of the decellularized liver. LSECs maintained
      hepatic function, and supported hepatocyte viability under blood perfusion in the
      engineered liver graft owing to their antithrombogenicity. This recellularization
      procedure could help produce practical liver grafts with blood perfusion.

PMID- 29338128
TI  - Clinical experience of laboratory follow-up with noninvasive prenatal testing
      using cell-free DNA and positive microdeletion results in 349 cases.
AB  - OBJECTIVE: Screening via noninvasive prenatal testing (NIPT) involving the
      analysis of cell-free DNA (cfDNA) from plasma has become readily available to
      screen for chromosomal and DNA aberrations through maternal blood. This report
      reviews a laboratory's experience with follow-up of positive NIPT screens for
      microdeletions. METHODS: Patients that were screened positive by NIPT for a
      microdeletion involving 1p, 4p, 5p, 15q, or 22q who underwent diagnostic studies
      by either chorionic villus sampling or amniocentesis were evaluated. RESULTS: The
      overall positive predictive value for 349 patients was 9.2%. When a microdeletion
      was confirmed, 39.3% of the cases had additional abnormal microarray findings.
      Unrelated abnormal microarray findings were detected in 11.8% of the patients in
      whom the screen positive microdeletion was not confirmed. Stretches of
      homozygosity in the microdeletion were frequently associated with a false
      positive cfDNA microdeletion result. CONCLUSIONS: Overall, this report reveals
      that while cfDNA analysis will screen for microdeletions, the positive predictive
      value is low; in our series it is 9.2%. Therefore, the patient should be
      counseled accordingly. Confirmatory diagnostic microarray studies are imperative
      because of the high percentage of false positives and the frequent additional
      abnormalities not delineated by cfDNA analysis.

PMID- 29338129
TI  - Three-dimensional visualization and volume quantification of pigment epithelium
      detachments.

PMID- 29338130
TI  - Correlation between morphological characteristics in spectral-domain-optical
      coherence tomography, different functional tests and a patient's subjective
      handicap in acute central serous chorioretinopathy.
AB  - PURPOSE: The purpose of this study was to identify quantitatively measurable
      morphologic optical coherence tomography (OCT) characteristics in patients with
      an acute episode of central serous chorioretinopathy (CSC) and evaluate their
      correlation to functional and psychological variables for their use in daily
      clinical practice. METHODS: Retinal thickness (RT), the height, area and volume
      of subretinal fluid (SRF)/pigment epithelium detachments were evaluated using the
      standardized procedures of the Vienna Reading Center. These morphologic
      characteristics were compared with functional variables [best-corrected visual
      acuity (BCVA), contrast sensitivity (CS), retinal sensitivity/microperimetry,
      fixation stability], and patients' subjective handicap from CSC using the
      National Eye Institute 25-item Visual Function Questionnaire (NEI VFQ-25).
      RESULTS: Data from 39 CSC patients were included in this analysis. Three
      different SRF height measures showed a high negative correlation (r = -0.7) to
      retinal sensitivity within the central 9 degrees , which was also negatively
      correlated with SRF area and volume (r = -0.6). The CS score and fixation
      stability (fixation points within 2 degrees ) showed a moderate negative
      correlation (r = -0.4) with SRF height variables. Comparison of the subjective
      handicap with morphological characteristics in spectral-domain (SD)-OCT showed
      SRF height had the highest correlation (r = -0.4) with the subjective problems
      reported and overall NEI VFQ-25 score. CONCLUSION: In conclusion, SRF height
      measured in SD-OCT showed the best correlation with functional variables and
      patients' subjective handicap caused by the disease and therefore seems to be the
      best variable to look at in daily clinical routine. Even though area and volume
      also show a correlation, these cannot be so easily measured as height and are
      therefore not suggested for daily clinical routine.

PMID- 29338131
TI  - Gross anatomy education for South African undergraduate physiotherapy students.
AB  - Eight faculties in South Africa offer undergraduate physiotherapy training with
      gross anatomy included as a basis for clinical practice. Little information
      exists about anatomy education for this student body. A 42-question peer-reviewed
      survey was distributed to physiotherapy gross anatomy course coordinators in all
      the eight faculties. Seven coordinators from six (75%) of the universities
      responded. Two respondents' data from the same university were pooled. Collected
      data show that staff qualifications and experience varied widely and high to
      average staff to student ratios exist between faculties. Direct anatomy teaching
      duration was 12.3 (SD +/-5.2) weeks per semester. Total number of weeks in
      courses per faculty was 27.6 (SD +/-5.7) varying widely between institutions.
      Calculable direct contact anatomy hours ranged between 100 and 308 with a mean of
      207.6 (SD +/-78.1). Direct contact hours in lectures averaged 3.9 (SD +/-1.6) per
      week and the average direct contact hours in practical sessions were 3.5 (SD +/
      1.8) per week. Dissection, prosection, plastinated models, surface anatomy, and e
      learning were available across faculties. Ancillary modalities such as vertical
      integration and inter-professional learning were in use. All faculties had
      multiple-choice questions, spot tests, and short examination questions. Half had
      viva-voce examinations and one had additional long questions assessment. Students
      evaluated teaching performance in five faculties. Four faculties were reviewing
      anatomy programs to consider implementing changes to anatomy curriculum or
      pedagogy. The findings highlighted disparity between programs and also identified
      the need for specific guidelines to develop a unified South African gross anatomy
      course for physiotherapy students.

PMID- 29338132
TI  - Tumour thickness, diameter, area or volume? The prognostic significance of
      conventional versus digital image analysis-based size estimation methods in uveal
      melanoma.
AB  - PURPOSE: The aim of this study was to compare conventional and novel size
      estimation methods' ability to predict survival in uveal melanoma (UM). METHODS:
      The study was designed as a retrospective consecutive chart review of patients
      with UM, enucleated between the years 1984 and 1993. Area and volume were
      estimated based on the largest histopathological cross-section, the second
      centroid theorem of Pappus and digital image analysis, correlated to overall and
      relative survival. RESULTS: Of 168 patients analysed, 20 (12%) of tumours were
      categorized as T1, 47 (28%) as T2, 67 (40%) as T3 and 19 (11%) as T4 (15 N/a). A
      total of 91 tumours with complete survival and measurement data were included and
      recategorized into small, medium and large volume groups. Increased separation of
      overall survival was seen compared with current American Joint Committee on
      Cancer T categories. Difference between the large and small volume groups was 8.6
      years (p = 0.001), compared to a difference of 5.6 years (p = 0.091) between T1
      and T4. Hazard ratio for all-cause mortality in the large versus small volume
      group was 2.6 compared to 1.9 for T4 versus T1. Relative survival rates for
      small, medium and large volumes were 62, 44 and 31% at 10 years, versus 50, 45,
      56 and 0% for T1, T2, T3 and T4. CONCLUSION: This study provides evidence that a
      novel UM volume estimation method might offer a practical and cost-efficient
      alternative to improve the prognostic value intrinsic to a tumour's size.

PMID- 29338133
TI  - Pimasertib-associated ophthalmological adverse events.
AB  - PURPOSE: To analyse ophthalmological adverse events associated with mitogen
      activated protein kinase kinase (MEK) inhibition with pimasertib treatment for
      metastatic cutaneous melanoma (CM). METHODS: In this prospective observational,
      cohort-based, cross-sectional study, eight patients treated with the MEK
      inhibitor pimasertib received a complete ophthalmic examination. This included
      Early Treatment of Diabetic Retinopathy Study best-corrected visual acuity,
      visual field testing, colour vision testing, slit-lamp examination, applanation
      tonometry, indirect ophthalmoscopy, digital colour fundus photography and optical
      coherence tomography (OCT). In selected cases, fluorescein angiography was
      performed. RESULTS: Serous subretinal fluid (SRF) developed in all patients,
      within a time frame of 9-27 days after the start of treatment. The fovea was
      involved in six of eight patients (75%). None of the patients with foveal SRF
      [excluding a patient who developed a bilateral retinal vein occlusion (RVO)]
      experienced visual symptoms. Subretinal fluid (SRF) decreased or resolved in all
      patients, despite continuation of study medication in six of eight patients
      (75%). Complaints in the CM patient (13%) consisted of experiencing a dark fleck
      in the inferior part of the visual field of the right eye 1 week after the start
      of treatment, due to an RVO. Subsequent intravitreal bevacizumab treatment
      resulted in functional and anatomical improvement. CONCLUSION: Patients with
      metastatic CM who are treated with the MEK inhibitor pimasertib are at high risk
      of development of ocular adverse events including serous retinopathy and possibly
      RVO, stressing the need of adequate ophthalmological follow-up including OCT
      during administration of pimasertib, despite the fact that SRF generally does not
      lead to ophthalmological complaints.

PMID- 29338134
TI  - Retinal oximetry is affected in multiple sclerosis.
AB  - PURPOSE: Structural and physiological abnormalities have been reported in the
      retina in patients with multiple sclerosis (MS). Retinal oximetry has recently
      detected changes in retinal oxygen metabolism in Alzheimer's disease and mild
      cognitive impairment. Our goal was to determine whether oxygen saturation in
      retinal blood vessels of patients with patients is different from that of a
      healthy population. METHODS: Oxygen saturation of haemoglobin was measured in
      retinal blood vessels, using imaging with spectrophotometric noninvasive retinal
      oximeter. Eight MS patients with history of optic neuritis were measured and
      compared to 22 healthy individuals matched in age and gender. RESULTS: Venular
      oxygen saturation was increased in patients with MS compared to healthy
      individuals (70.7 +/- 3.4% versus 66.2 +/- 4.7; p = 0.021, mean +/- SD). The
      arteriovenous (AV) difference was lower in patients with MS compared to healthy
      (26.6 +/- 3.6% versus 30.5 +/- 4.8%; p = 0.049). There was no difference measured
      in arterioles when patients with MS (97.3 +/- 1.7%) and healthy individuals (96.7
      +/- 2.8%) were compared. CONCLUSION: Increased venular oxygen saturation and
      lower AV difference in patients with MS may indicate reduced oxygen uptake. This
      may be due to less oxygen demand following atrophy and may be a useful objective
      biomarker for MS. Further studies are needed to confirm and expand these
      findings.

PMID- 29338135
TI  - The influence of type 2 diabetes mellitus on the frequency and complexity of
      ventricular arrhythmias and heart rate variability in patients after myocardial
      infarction.
AB  - Background/Aim: After myocardial infarction arrhythmic cardiac deaths are
      significantly more frequent compared to non-arrhythmic ones. The aim of the study
      was to investigate the influence of type 2 diabetes mellitus (T2DM) on the
      frequency and complexity of ventricular arrhythmias after myocardial infarction.
      Methods: The study included 293 patients, mean age 59.5 +/- 9.21 years, who were
      at least six months after acute myocardial infarction with the sinus rhythm,
      without atrioventricular blocks and branch blocks. In the clinical group 95
      (32.42%) patients were with T2DM, while 198 (67.57%) patients were without
      diabetes. All of the patients were subjected to the following procedures:
      standard ECG according to which the corrected QT dispersion (QTdc) was
      calculated, exercise stress test, and 24-hour holter monitoring according to
      which, the four parameters of time domain of heart rate variability (HRV) were
      analyzed: standard deviation of all normal RR intervals during 24 hours (SDNN),
      standard deviation of the averages of normal RR intervals in all five-minute
      segments during 24 hours (SDANN), the square root of the mean of the sum of the
      squares of differences between adjacent normal (RMS-SD), and percentage of
      consequtive RR intervals which differed for more than 50 ms during 24 hours (NN >
      50 ms). Results: In patients after myocardial infarction, patients with T2DM had
      significantly higher percentage of frequent and complex ventricular arrhythmias
      compared to the patients without diabetes (p < 0.001). The patients with T2DM had
      significantly higher percentage of residual ischemia (p < 0.001), and arterial
      hypertension (p < 0.001), compared to patients without diabetes. The patients
      with T2DM had significantly lower values of HRV parameters: SDNN (p < 0.001);
      SDANN (p < 0.001); RMS-SD (p < 0.001), and NN > 50 ms (p < 0.001), and
      significantly higher values of QTdc (p < 0.001) compared to the patients without
      diabetes. Conclusion: The study showed that type 2 diabetes mellitus has
      significant influence on ventricular arrhythmias, HRV parameters and QT
      dispersion in patients after myocardial infarction.

PMID- 29338137
TI  - Morphological embryo selection: an elective single embryo transfer proposal.
AB  - OBJECTIVE: To describe a patient selection method for elective single embryo
      transfer (eSET), emphasizing inclusion criteria and results. METHODS: This
      retrospective study included all cases seen in a private clinic between June 2011
      and December 2016, in La Paz, Bolivia (3600 meters above sea level). Elective
      single embryo transfer was the method of choice in 34 IVF/ICSI cycles, all in the
      blastocyst stage. Gardner's blastocyst classification criteria were used. Between
      the two stages of the study (July 2015), each embryo grade implantation rate was
      recalculated, which led to the expansion of the inclusion criteria. RESULTS: The
      clinical pregnancy rate of the 34 cases in the first transfer group was 55.9%
      (19/34). Twin or multiple pregnancies did not occur. The cumulative pregnancy
      rate to date is 64% [(19+3)/34]. The first stage comprised 2.56% (12/468) of the
      patients offered elective single embryo transfers; the implantation rate was
      58.3% (7/12). In the second stage, 14.29% (22/154) of the patients were eligible,
      and the implantation rate was 54.55% (12/22). CONCLUSIONS: The implementation of
      an eSET program based on in-depth morphological embryo assessment combined with
      the calculation of the implantation potential of each embryo grade led to
      acceptable clinical outcomes and fewer multiple pregnancies in patients
      transferred two embryos. Each clinic should be aware of the implantation rates of
      each embryo grade in its own setting.

PMID- 29338136
TI  - Plasmatic estradiol concentration in the mid-luteal phase is a good prognostic
      factor for clinical and ongoing pregnancies, during stimulated cycles of in vitro
      fertilization.
AB  - OBJECTIVE: To evaluate the predictive efficiency of serum estradiol (E2)
      concentration in the mid-luteal phase regarding chemical, clinical, and ongoing
      pregnancies, in patients subjected to IVF/ICSI with fresh embryo transfer.
      METHODS: One hundred and forty-three patients undergoing IVF/ICSI met all the
      inclusion criteria for the present study. Most of the patients used antagonists,
      final maturation was achieved with recombinant chorionic gonadotrophin (HCG), and
      embryo transfer took place on days 3 to 5, but mostly on day 4. The luteal phase
      was supplemented with estradiol valerate 6 mg/day and vaginal micronized
      progesterone 600 mg/day. There was no exclusion of patients in the embryo
      transfer group due to age or ovarian reserve. All patients with estradiol and
      chorionic gonadotrophin (betaHCG) dosage on the day of transfer, day 7, were
      included. We assessed the following variables, initially regarding age: number of
      eggs collected, formed embryos, embryos transferred, day of transfer, transfer
      type, estradiol and chorionic gonadotropin. Next, we evaluated these elements at
      three different ranges of estradiol concentrations (<200 pg/ml, 200-500 pg/ml,
      and >500 pg/ml), comparing these parameters in pregnant (P) and non-pregnant (NP)
      patients. RESULTS: Data analysis by age group in P and NP patients showed
      significant differences in the mean values of the variables E2 and betaHCG, TD7.
      Mean serum estradiol levels in P and NP in the three age groups were: <35 years,
      835/417 p=0.0006, 35-39 years 833/434 p=0.0118, >39 years, 841/394 p=0.0012.
      There was also a significant difference in pregnancy rates in the group >500
      pg/ml of estradiol concentration (63.4%, p=0.0096). The likelihood of chemical
      and clinical abortions for the estradiol ranges were: 38.46%, involving the two
      first ranges versus 15.15% for a concentration >500 pg/ml, p=0.0412 and 5.26% for
      a concentration >900 pg/ml, p=0.0105. The Pearson correlation coefficient for HCG
      and estradiol was r=0.5108. CONCLUSION: This study showed the prognostic value of
      E2 in the mid-luteal phase (TD7) for chemical, clinical, and ongoing pregnancies,
      and its concentration suggested that there is a moderately positive correlation
      with betaHCG levels.

PMID- 29338138
TI  - Could cryopreserved human semen samples be stored at -80 degrees C?
AB  - OBJECTIVE: To evaluate storage time effects in cryopreserved human semen samples,
      kept in the freezer at a controlled temperature of -80 degrees C, on sperm
      viability after thawing. METHODS: We used 20 semen samples. Each sample was
      cryopreserved in 10 fingers, which were divided into five groups: one group was
      kept in cryogenic canisters throughout the experiment(control), and four groups
      were kept in a VIP Ultra Low MDF-U76V- PE freezer, with the temperature set at 
      80 degrees C, for 24, 48, 72 and 96 hours, respectively. After the exposure time,
      the samples were stored in cryogenic canisters after being thawed. The analyzed
      parameters were: motility, vitality and mitochondrial activity. RESULTS: After
      thawing, we noticed decreased sperm motility, vitality and mitochondrial
      activity, when comparing the tested groups with the control group, as well as a
      progressive reduction in the analyzed parameters between the times evaluated.
      CONCLUSIONS: Cryopreservation of semen samples at -80 degrees C is potentially
      harmful to sperm viability, causing damage when submitted to longer exposure
      times.

PMID- 29338139
TI  - Occurrence of ovarian follicular dominance during stimulation for IVM impacts
      usable blastocyst yield.
AB  - OBJECTIVE: To evaluate the influence of ovarian follicular dominance on the
      outcome of oocyte in-vitro maturation. METHODS: This retrospective cohort study
      included 21 patients with polycystic ovaries or polycystic ovary syndrome
      (Rotterdam criteria, 2004) subjected to 24 invitro maturation (IVM) cycles
      between October 2015 and January 2017. Patients undergoing IVM received minimal
      gonadotropin stimulation starting on day 2 or 3 of the cycle; ovum pick-up
      typically occurred on days 6 to 8. No hCG-trigger shot was given. Following 30h
      of IVM, mature oocytes were inseminated by ICSI and the resulting embryos
      cultured up to the blastocyst stage. RESULTS: Ovarian follicular dominance was
      observed in nine of the 24 IVM cycles. Oocyte IVM yielded an overall maturation
      rate of 69.3+/-23.8%, and no difference was observed when the groups with or
      without a dominant follicle were assessed independently. The rates of
      fertilization and usable blastocysts per fertilized oocyte, mature oocyte
      (Metaphase II) or cumulus-oocyte-complex were nearly three times higher (28.7+/
      22.5%) in the group without ovarian follicular dominance. No differences were
      found in the clinical pregnancy rates attained by the individuals with or without
      a dominant follicle after 21 vitrified-warmed blastocyst transfer cycles.
      CONCLUSION: Occurrence of ovarian follicular dominance during hormonal
      stimulation for in-vitro maturation negatively impacted embryological outcomes.
      Strategies devised to limit the appearance of ovarian follicular dominance must
      be further explored.

PMID- 29338141
TI  - Comparison of the efficacy of femoral nerve block and fascia iliaca compartment
      block in patients with total knee replacement.
AB  - BACKGROUND: Blocking the femoral nerve reduces postoperative pain and analgesic
      consumption in patients who have undergone total knee and hip replacement
      surgery. A limited number of studies have compared the efficacy of the fascia
      iliaca compartment and femoral nerve block techniques. Therefore, this study
      aimed to investigate the analgesic effectiveness of fascia iliaca compartment
      block (FIB) and femoral nerve block using ultrasound. METHODS: A total of 100
      patients were included in the study. Patients were divided into two randomized
      and equal groups (Group I had patients who underwent fascia iliaca compartment
      block, N.=50; Group II had patients who underwent femoral nerve block, N.=50).
      Visual Analogue Scale levels (VAS) in the postoperative 30th min and 1st, 2nd,
      6th, 12th and 24th hours and the amounts of analgesic consumption were recorded.
      The Quality of Recovery-40 (QoR-40) questionnaire was completed by patients 24
      hours after surgery. RESULTS: The VAS level at the 24th hour was significantly
      lower in Group I compared to Group II. Analgesic consumption between 0-30th
      minutes was lower in Group II than in Group I; however, it was significantly
      lower in the 6-24 hours of Group I compared to Group II. The QoR-40 score was
      found to be significantly higher in Group I than Group II. CONCLUSIONS: Femoral
      nerve block provided more potent analgesia in the first six hours after
      operation. After six hours, FIB demonstrated better pain control. The quality of
      postoperative recovery was higher in patients with fascia iliaca compartment
      block.

PMID- 29338140
TI  - Primary pyomyositis in North India: a clinical, microbiological, and outcome
      study.
AB  - BACKGROUND/AIMS: Pyomyositis is an infective condition with primary involvement
      of the skeletal muscles. There is sparse recent literature on patients with
      pyomyositis. METHODS: This study was carried out at emergency services of a
      tertiary care center located in subtropical area of Indian subcontinent. RESULTS:
      Sixty-two patients of primary pyomyositis formed the study cohort. Mean age of
      occurrence was 29.9 +/- 14.8 years. There were 54 men. Twelve patients had
      underlying medical diseases. Muscle pain was seen in all 62 patients. Forty-eight
      patients (77.4%) had the fever. Most common site of involvement was thigh muscles
      (n = 29, 46.8%). Forty-nine patients (79%) presented in the suppurative stage of
      illness. Patients with comorbidities were older (age: median 36 years
      [interquartile range (IQR), 25 to 47] vs. 24 years [IQR, 16 to 35], p = 0.024),
      had higher culture positivity with gram-negative organisms (8/9 [88.89%] vs. 6/29
      [20.69%], p = 0.001). Importantly, higher number of these patients received
      inappropriate antibiotics initially. Patients with positive pus culture result
      had higher complication rate (32/38 [84.21%] vs. 10/18 [55.56%], p = 0.044). Six
      patients (9.7%) had in-hospital mortality. Lower first-day serum albumin, initial
      inappropriate antibiotic therapy, and advanced form of the disease at
      presentation were associated with increased in-hospital mortality. CONCLUSIONS:
      Primary pyomyositis is not an uncommon disease entity. Patients with
      comorbidities were more likely to receive initial inappropriate antibiotic
      therapy. Patients with positive pus culture report had the higher rate of
      complications. Lower first-day serum albumin, initial inappropriate antibiotic
      therapy and advanced form of the disease at presentation were associated with
      increased in-hospital mortality.

PMID- 29338142
TI  - Patient-controlled epidural analgesia with and without basal infusion using
      ropivacaine 0.15% and fentanyl 2gamma/mL for labor analgesia: a prospective
      comparative randomized trial.
AB  - BACKGROUND: Patient-controlled epidural analgesia (PCEA) is a common practice for
      labor pain relief. This study aimed to compare two different settings of a PCEA
      device using the same solution to obtain labor analgesia. METHODS: Fifty-two
      parturients were randomly allocated to receive ropivacaine 0.15% and fentanyl 2
      gamma/mL via a PCEA device either as a background infusion of 5 mL/h plus 5 mL
      demand bolus doses with 10-minute lockout (group B/D, N.=26) or as only demand
      bolus doses of 5 mL with 10-minute lockout (group D, N.=26). The primary outcome
      was the total volume of local anesthetic administrated during labor; secondary
      outcomes included the analgesic efficacy and the effects on maternal and neonatal
      outcomes. RESULTS: No statistical difference was observed between the groups
      concerning demographic characteristics, duration of first and second stages of
      labor, administration of oxytocin and ephedrine, rescue doses, instrumental
      delivery, Bromage Scale, maternal side effects and satisfaction, neonatal Apgar
      scores and pH. The total volume of local anesthetic was greater in group B/D
      compared to group D (P=0.015). A statistically significant difference was
      detected in VAS scores only at the end of the second stage (P=0.036) and at 60
      minutes from the test dose administration (P=0.022) and with group D exhibited
      higher pain scores than group B/D. The incidence of breakthrough pain (VAS>4) was
      higher in group D compared with group B/D (P=0.035). CONCLUSIONS: The addition of
      background infusion plus PCEA demand bolus doses increased local anesthetic
      consumption and reduced breakthrough pain without affecting maternal satisfaction
      and neonatal outcomes.

PMID- 29338143
TI  - Anesthesiology Resident Induction Month: a pilot study showing an effective and
      safe way to train novice residents through simulation.
AB  - BACKGROUND: The transition of new residents from medical school to the post
      graduate clinical environment remains challenging. We hypothesized that an
      introductory simulation course could improve new residents' performance in
      anesthesiology. METHODS: The Anesthesiology Residents Induction Month (ARIM)
      program was designed as a non-clinical simulation training program aiming at
      providing the theoretical and practical skills to safely approach, as junior
      anesthesiologists, the operating rooms. For each participant, specific knowledge,
      procedural skills and non-technical performance were assessed with a pre and post
      test approach, before and immediately after the participation in the study.
      RESULTS: Fifteen first-month residents participated in the study. As compared to
      pre-test, residents significantly improved in all three evaluated areas. Pre-test
      knowledge assessment mean improved from 56% to 73% in the post-test (P<0.001). In
      the procedural skills assessment, pre-test mean improved from 43% to 77%
      (P<0.001) and non-technical skills assessment improved from 3.17 to 4.61 (in a
      scale out of seven points) in the post-test (P<0.001). CONCLUSIONS: Data suggest
      that an intensive simulation-based program can be an effective way for first-year
      residents to rapidly acquire and develop basic skills specific to anesthesiology.
      There might be benefits to begin residency with a training program aiming at
      developing and standardizing technical and non-technical skills.

PMID- 29338144
TI  - Mortality and long-term quality of life after percutaneous tracheotomy in
      Intensive Care Unit: a prospective observational study.
AB  - BACKGROUND: Quality of life and mortality after percutaneous dilatational
      tracheotomy (PDT) has been poorly investigated. The aims of this study were to
      evaluate the independent risk factors for Intensive Care Unit (ICU) mortality and
      investigate quality of life over the first year after PDT in critically ill
      patients. METHODS: This was a prospective, single-center, cohort study performed
      in a tertiary care University Hospital, enrolling consecutive ICU patients
      requiring elective PDT, collecting data during the tracheotomy procedure and the
      ICU stay. Follow-up was performed at three, six and twelve months after PDT. The
      medical interview included the Euro Quality of Life questionnaire comprising five
      dimensions (mobility, self-care, usual activities, pain/discomfort,
      anxiety/depression). RESULTS: A total of 137 patients were included in the study.
      In the multivariate analysis, ICU mortality was independently associated with age
      (OR 1.089; P=0.003) and SAPS II (OR 1.047; P=0.003), and inversely with
      neurologic disease (OR 0.162; P=0.004). Mortality increased over time (ICU
      mortality 26.7%; in-hospital mortality 43.1%; 3-months mortality 47.4%; 6-months
      mortality 61.3%; and 1-year mortality 70.8%; P=0.0001). Tracheostomized patients
      due to respiratory disease had a higher ICU mortality (50%) compared to those
      with neurological disease (13.6%). quality of life (QoL) of tracheostomized
      patients was severely compromised at 3-months (QoL: 17, 15-19), 6-months (QoL:
      17; 16-19), while moderately compromised at 1-year (QoL: 13; 9-16). A subgroup
      analysis showed better QoL at 3-months, 6-months and 1-year in respiratory
      compared to neurological tracheostomized patients (P=0.01). CONCLUSIONS: Patients
      baseline characteristics and indication for PDT procedure are important
      determinants of in-ICU mortality and QoL in tracheostomized patients.

PMID- 29338145
TI  - Association between Bispectral Index System and airway obstruction: an
      observational prospective cohort analysis during third molar extractions.
AB  - BACKGROUND: Sedation regimes during oral procedures frequently associated with
      airway obstruction. The aim of this study was to define the association of
      Bispectral Index (BIS) to the depth of sedation and airway obstruction events.
      METHODS: Forty-seven patients between 14-21 years old, who were candidates for
      3rd molar teeth extraction, were enrolled in this study. Patients received a
      total of 4 mg midazolam, 100 microgram fentanyl followed by titrated incremental
      propofol in 10 mg. The Richmond Agitation Sedation Score (RASS) was used to
      assess the depth of sedation. Each patient was attached to BIS monitor, while
      clinicians were not involved in the data collection process. Apnea, airway
      obstruction, O2 saturation, timing and interventions for controlling the
      situation were recorded. All data was synchronized with BIS data monitoring.
      RESULTS: The results show that 97.5% of cases were ASA 1 and 2, with average age
      of 17.3 years (+/-1.4) and a median BMI of 26.1. By using linear regression, for
      every unit decrease of median RASS (less than zero), there was 1.78 decrease in
      mean BIS Score (P=0.045, 95% CI: 0.08-3.47). The mean BIS Index (over 1 minute)
      with airway obstruction was 64 (+/-10.2), which was significantly lower than the
      BIS during non-airway obstruction (77+/-11.6), (P<0.001). By using logistic
      regression analysis, for every on unit increase in BIS Index, there is 24%
      decrease in odds in having airway obstruction (P=0.0009, 95% CI: 0.65-8.94).
      CONCLUSIONS: This study demonstrates that the BIS could potentially be a valid
      continuous monitoring method to avoid airway obstruction during sedation for
      patients undergoing dental surgery.

PMID- 29338146
TI  - The effect of various doses of infusion solutions on the endothelial glycocalyx
      layer in laparoscopic cholecystectomy patients.
AB  - BACKGROUND: The endothelial glycocalyx is located on the luminal side of blood
      vessels and maintains vessel integrity. This study analysed how various dosages
      of infusion affected the secretion of atrial natriuretic peptide (ANP) and
      potential glycocalyx damage in patients undergoing laparoscopic cholecystectomy.
      We hypothesised that the liberal administration of Ringer's solution during the
      operation can cause iatrogenic hypervolemia with releasing of ANP and glycocalyx
      damage. METHODS: The study included 90 patients with American Society of
      Anesthesiologists' (ASA) class I and II, in good cardiopulmonary health, who were
      assigned to one of three groups: Restrictive group, which received 1 mL/kg/hr
      intraoperatively and six hours postoperatively; Low liberal group, which received
      5 mL/kg/hr of Ringer's solution intraoperatively and six hours postoperatively
      and High liberal group, which received 15 mL/kg/hr intraoperatively and 10
      mL/kg/hr six hours postoperatively. We measured patients' concentrations of
      glycocalyx constituents, ANP, markers of kidney and liver function, C-reactive
      protein (CRP), and albumine at three time points. We also measured noinvasive
      hemodynamics, the correlation between ANP secretion and the concentration of
      glycocalyx components. RESULTS: We found a significantly higher concentrations of
      hyaluronic acid and syndecan-1 and more ANP secretion in the High liberal group
      than in the other groups. We also observed a positive correlation between ANP
      secretion and glycocalyx constituent concentration. Markers of kidney and liver
      function were normal, suggesting preservation of splanchnic perfusion and global
      hemodynamics. CONCLUSIONS: Measuring the endothelial glycocalyx constituents in
      circulating blood could be a marker of intraoperative volume overload during
      laparoscopic operations.

PMID- 29338147
TI  - Effect of therapeutic hypothermia on survival and neurological outcome in adults
      suffering cardiac arrest: a systematic review and meta-analysis.
AB  - INTRODUCTION: The aim of this review was to determine current evidence for the
      effect of therapeutic hypothermia (TH) on survival and neurological outcome in
      adults suffering cardiac arrest (CA). EVIDENCE AQUISITION: We searched the
      Cochrane Controlled Trials Register, MEDLINE, EMBASE and NLM databases from 2000
      to 2017 using the following terms: hypothermia, cooling, therapeutic, cardiac
      arrest, resuscitation, cardiopulmonary, CPR. Studies were eligible if they
      compared TH versus normothermic management in adult humans sustaining CA.
      Randomized controlled trials (RCT), pilot studies and observational trials were
      included. EVIDENCE SYNTHESIS: Ten studies involving 3259 patients were included
      in meta-analysis. Pooling all eligible studies showed a favorable effect for TH
      on survival and neurological recovery. However, sensitivity analysis for RCTs
      showed no benefit on either outcome, while observational trials showed benefit
      for neurological recovery with just marginally significant benefit regarding
      survival. Studies including patients with shockable rhythms demonstrated benefit
      for both outcome measures, while those including patients with any rhythms
      demonstrated benefit for neurological recovery but not for survival. TH did not
      benefit patients with non-shockable rhythms. Trials using external cooling
      favored TH regarding survival and neurological outcome but those using systemic
      cooling with or without external cooling did not show such benefit. When the
      overall incidence of complications was pooled, there was a statistically
      significant shift in odds ratio favoring normothermic management over TH.
      CONCLUSIONS: Evidence from RCTs suggests TH does not improve survival or
      neurological outcome, while observational trials favor TH over normothermia. TH
      may be attended with higher risk for complications.

PMID- 29338148
TI  - Novel applications of bedside monitoring to plumb patient hemodynamic state and
      response to therapy.
AB  - Hemodynamic monitoring is essential during the treatment of the critically ill in
      order to address the hemodynamic alterations and assess the response to
      treatment. Traditionally classified causes of shock and underlying
      pathophysiological mechanisms are often neglected by resuscitative strategies
      included in the guidelines. Most of hemodynamic management focuses on the ability
      to early recognize patients susceptible to increase cardiac output (CO) and mean
      arterial pressure (MAP) after a defined fluid challenge by eliciting Starling's
      law of the heart, and less is known of the ones presenting in shock and not
      volume responsive. All this influences the application of hemodynamic monitoring
      tools and their interpretation. Functional hemodynamic monitoring strategies,
      aiming to overcome limitations of traditional static pressures measurements, have
      been developed and recently acknowledged by guidelines for the treatment of
      septic shock. Nevertheless, those techniques share the same limitations of
      previous ones, being poorly reliable in various common situations such as in
      spontaneous breathing patients, right ventricular dysfunction of several causes
      or if arrhythmia occurs. Echocardiography has now become commonplace in the
      evaluation of the hemodynamic profile in the critically ill and mastering this
      technique is important in order to interpret pathophysiological patterns behind
      hemodynamic alteration while at the same time, screening for unexpected findings.
      More recently, pathophysiological and echocardiographic-based approaches have
      been introduced to investigate ventriculo-arterial coupling, the relationship
      between both left and right heart and the relative circulatory bed. Such
      techniques allowed establishing that in many critically ill scenarios, coupling
      between the heart and the circulation is inefficient and probably that is the
      reason why in this case hemodynamic restoration cannot be achieved by standard
      approaches. Combining echocardiography to better understand and treat in real
      time pathophysiological determinants of altered hemodynamic states with
      functional approaches seems to be the key to plumb hemodynamic states although it
      remains to be demonstrated if this tailored approach will improve patient
      outcome.

PMID- 29338149
TI  - Injection pressure mapping of intraneural vs. perineural injections: further
      lessons from cadaveric studies.
AB  - BACKGROUND: The aim of the study was to investigate the difference between
      intraneural and perineural injection pressures in human cadavers. Targeted nerves
      included the cervical roots, the supraclavicular and infraclavicular brachial
      plexus, the sciatic-subgluteal nerve and the common peroneal and tibial nerves.
      METHODS: Ten readings were obtained for each nerve location. Over ten seconds, 1
      mL of 0.9% NaCl was injected - deliberately slower than in clinical practice to
      eliminate the risk of aberrant readings relating to the speed of injection.
      Perineural injections occurred at least 1 mm outside the epineurium. After
      pressure recordings were completed 0.1mL of dye was injected, and dissection
      performed to confirm needle placement. Ultrasound and dissection images were
      matched with light microscopy pictures for all locations. RESULTS: The average
      pressure for intraneural injections was 24.1+/-5.7 psi and 6.1+/-2.1 psi for
      perinereural. The average injection pressure generated for the cervical trunk,
      supraclavicular, infraclavicular, sciatic subgluteal, peroneal and tibial nerves
      respectively were 31.2+/-6.0 psi, 24+/-15.0 psi, 23.4+/-9.5 psi, 22.6+/-8.8 psi
      19.7+/-6 psi, 17+/-7.3 psi intraneurally and 6.1+/-2.0 psi, 9.1+/-5.5 psi, 10+/
      4.9 psi, 6+/-2.4 psi, 6+/-2.4 psi and 7+/-2.5 psi perineurally. For intraneural
      injections statistically significant differences were demonstrated between the
      peroneal and tibial nerves compared to cervical roots/trunks/division/cords of
      brachial plexus. CONCLUSIONS: The study has consistently demonstrated
      statistically significant differences between intraneural and perineural
      injection pressures. It effectively created a "map" of intraneural injection
      pressures for the most common peripheral nerves blocks and demonstrated a pattern
      between proximal and distal locations. The study also revealed limitations of
      either techniques, ultrasound and injection pressure monitoring reinforcing the
      concept of their simultaneous application.

PMID- 29338150
TI  - The role of cannabinoids in pain control: the good, the bad, and the ugly.
AB  - Cannabinoids appear to possess many potential medical uses, which may extend to
      pain control. A narrative review of the literature has found a variety of studies
      testing botanical and synthetic cannabinoids in different pain syndromes (acute
      pain, cancer pain, chronic noncancer pain, fibromyalgia pain, migraine,
      neuropathic pain, visceral pain, and others). Results from these studies are
      mixed; cannabinoids appear to be most effective in controlling neuropathic pain,
      allodynia, medication-rebound headache, and chronic noncancer pain, but do not
      seem to offer any advantage over nonopioid analgesics for acute pain.
      Cannabinoids seem to work no better than placebo for visceral pain and conferred
      only modest analgesic effect in cancer pain. Cannabinoids do many good things -
      they appear to be effective in treating certain types of pain without the issues
      of tolerance associated with opioids. Negatively, marijuana currently has a very
      murky legal status all over the world - laws regulating its use are inconsistent
      and in flux. Thus, both patients and prescribers may be unsure about whether or
      not it is an appropriate form of pain control. Cannabinoid-based analgesia has
      been linked to potential memory deficits and cognitive impairment. A great deal
      more remains to be elucidated about cannabinoids which may emerge to play an
      important role in the treatment of neuropathic and possibly other painful
      conditions. There remains a great deal more to learn about the role of
      cannabinoids in pain management.

PMID- 29338151
TI  - Oral prolonged-release oxycodone/naloxone offers equivalent analgesia to
      intravenous morphine patient-controlled analgesia after total knee replacement. A
      randomized controlled trial.
AB  - BACKGROUND: The purpose of this study was to determine whether oral prolonged
      release oxycodone-naloxone combination (OXN) could provide equivalent analgesia
      and a side-effect profile similar to intravenous morphine patient-controlled
      analgesia (IVPCA) for the control of pain in the immediate postoperative period
      after total knee replacement (TKR). METHODS: All patients received a sciatic
      nerve block with 0.3% ropivacaine 15 mL, femoral nerve block with 0.5%
      ropivacaine 20 mL, spinal anesthesia and postoperative continuous femoral nerve
      infusion (ropivacaine 0.2% 4 mL/h). After surgery, patients were randomly
      allocated to receive either 10 +10 +5 mg controlled release OXN oral
      administration 12 hourly or IVPCA with morphine (2 mg bolus, no basal infusion).
      The primary outcome was the average rest and dynamic pain for the first 48 h
      postoperatively. Secondary outcomes were: post operative nausea vomiting (PONV)
      and the total morphine consumption. RESULTS: OXN group experienced better pain
      control at rest during the first (0.89+/-1.54 vs. 1.27+/-1.82, P=0.0019) and
      second (1.03+/-1.69 vs. 1.65+/-2.05, P=0.0006) postoperative period. There was no
      statistically significant difference in pain score during movement between the
      two groups. The secondary outcome measures showed no significant differences in
      the total morphine consumption (12.04+/-1.1 vs. 11.46+/-3.7 mg, P=0.20) or PONV
      (0.6+/-0.8 vs. 0.8+/-1.0, P=0.40). CONCLUSIONS: This study show that in the
      immediate postoperative period after TKR, the patients receiving oral prolonged
      release OXN experienced the same to better pain control than those receiving
      morphine IVPCA, with a similar degree of PONV.

PMID- 29338152
TI  - Generation and Characterization of Siglec-F-Specific Monoclonal Antibodies.
AB  - Siglec-F (SF) is a surface glycoprotein expressed by mouse eosinophils and
      induces caspase- and mitochondria-dependent apoptosis after engagement with its
      cognate ligand or specific antibodies. This targeting eosinophils by monoclonal
      antibodies may help diverse diseases associated with increased frequency of
      eosinophils including allergy and asthma. In this paper, production of murine and
      rat monoclonal antibodies (mAbs) against Siglec-F has been addressed. Balb/c mice
      were immunized with siglec-F1 (SF1) and siglec-F2 (SF2) synthetic peptides
      conjugated to a carrier protein. Rats were immunized with Chinese hamster ovary
      CHO cells overexpressing Siglec-F (CHO-SF) or with Siglec-F-human immunoglobulin
      FC fusion protein (CHO-SF-Ig). Hybridomas were produced by standard protocol and
      screened for their reactivity by enzyme-linked immunosorbent assay (ELISA),
      western blotting (WB), and flow cytometry. In parallel, polyclonal antibodies
      were generated in New Zealand White rabbits immunized with SF1 and SF2 peptides.
      Three mouse and three rat mAbs were generated against synthetic peptides and SF
      Ig, respectively. All mouse monoclonal and rabbit polyclonal antibodies reacted
      well with immunizing molecules in ELISA and detected specific band of Siglec-F in
      WB. However, they failed to detect native molecule in flow cytometry analysis.
      Quite the contrary, rat mAbs did not reacted with the denatured protein in WB,
      instead exhibited significant reactivity with CHO-SF cells in flow cytometry.
      Based on the heavily glycosylated nature of Siglec-F, it seems that generation of
      anti-SF antibodies able to detect native protein needs a properly folded molecule
      for immunization. Monoclonal antibodies reported here are invaluable tools for
      studying linear and conformation epitopes of SF and tracing mouse eosinophils.

PMID- 29338153
TI  - Association Study of CD226 and CD247 Genes Single Nucleotide Polymorphisms in
      Iranian Patients with Systemic Sclerosis.
AB  - CD247 and CD226 play important roles in signaling of lymphocytes. Single
      nucleotide polymorphisms (SNPs) of genes encoding CD247 and CD226 have been
      associated with the risk of several autoimmune disorders. This study aimed to
      evaluate the possible association between CD226 and CD247 genes SNPs and risk of
      systemic sclerosis (SSc) in Iranian population. Study participants were 455 SSc
      patients and 455 age, sex and ethnic -matched healthy individuals. Genotyping of
      rs2056626 and rs763361 at CD247 and CD226 genes, respectively, was carried out
      using TaqMan MGB-based allelic discrimination real-time PCR. Neither alleles nor
      genotypes of both SNPs showed significant association with the risk of SSc.
      Furthermore, association analysis of the genotypes with clinical manifestations
      of the disease revealed that rs763361 variants were associated with the forced
      vital capacity (FVC) in SSc patients. Our results suggest that genetic variants
      of CD226 and CD247 genes may not be a contributing factor in pathogenesis of SSc
      in Iranian population.

PMID- 29338154
TI  - Characteristics, Etiology and Treatment of Pediatric and Adult Anaphylaxis in
      Iran.
AB  - Despite the increasing prevalence of anaphylaxis, there is little information
      about the characteristics and practice of healthcare providers in treating
      anaphylaxis, so this study was conducted to record the characteristics and
      therapeutic approaches of anaphylaxis from May 2012 until April 2015, the data of
      all patients diagnosed with anaphylaxis in the Allergy department of three
      referral university hospitals in Tehran, Iran were recorded. Thereafter, the
      demographics, clinical features, triggers and therapeutic approach were
      evaluated. This study investigated 136 individuals, 64 males (47%) between 6
      months and 68 years old, as well as 72 others (52.94%) under 18 years of age
      (pediatric). The following were the most common organs involved: Skin 86.02%
      (pediatric 91.66% vs adult 79.68%), respiratory tract 51.47% (pediatric 43.05% vs
      adult 60.93%), cardiovascular 50.73% (pediatric 54.16% vs adult 46.87%),
      gastrointestinal 20.58% (pediatric 27.7% vs adult 12.5% ) and neurologic system
      5.88% (only in adults). The following were the most identified causing foods 69
      (50.37%)[42 pediatric (children) and 27 adults], drugs 34( 25%)[14 pediatric and
      20 adults], idiopathic 16( 11.77%)[3 pediatric and 13 adults], insect sting 7(
      5.15%)[3 pediatric and 4 adults] , exercise 6( 4.42%) [1 pediatric and 5 adults].
      Milk, egg and wheat were the most common causative foods in pediatric cases but
      sesame, as well as egg and milk were the most common causes in adults.
      Epinephrine injection, auto injector epinephrine prescription as a discharging
      plan and referral to an allergist were: 10.78, 1.96 and 7.8 %, respectively. In
      this case series we found that, cutaneous, respiratory, cardiovascular and
      gastrointestinal complains were the most common manifestations and food, drug and
      idiopathic were the most common causes.In this study, the diagnosis of
      anaphylaxis, epinephrine subscription and referral to an allergist were
      significantly lower in comparison to other studies.

PMID- 29338155
TI  - Association between Caregiver Exposure to Toxics during Pregnancy and Childhood
      onset Asthma: A Case-control Study.
AB  - The aim of this study was to evaluate the associations between caregiver-reported
      use of medications, alcohol, cigarette and/or waterpipe (WP), and exposure to
      pesticides/detergents during pregnancy with childhood-onset asthma. The study
      design consisted of a case-control study, conducted between December 2015 and
      April 2016, recruited 1503 children, aged between 3-16 years old. A questionnaire
      assessed the sociodemographic characteristics (age, gender, education level of
      both parents), the family history of asthma, and other known risk factors of
      asthma (heating system at home, child history of recurrent otitis, humidity in
      the house, child went to a daycare, smoking and drinking alcohol during
      pregnancy, exposure to pesticides and detergents). The multivariate analysis
      showed that children living in North and South Lebanon and the children living in
      areas where pesticides are frequently used had an increased risk of asthma
      (ORa=1.625, CI 1.034-2.554, p=0.035, ORa=13.65, CI 3.698-50.385; p<0.001 and
      ORa=3.307, CI 1.848-5.918, p<0.001 respectively). Smoking WP during pregnancy and
      cigarette during lactation would increase the risk of asthma in children
      (ORa=6.11; CI 1.244-30.008; p=0.026 and ORa=3.44; CI 1.024-11.554; p=0.046
      respectively). We conclude that asthma may originate from the environmental
      exposure to toxics such as pesticides and tobacco (cigarettes and WP) or to
      alcohol and prescribed medications during pregnancy and lactation. Spreading
      awareness by health professionals about these preventable causes can help educate
      the parents and children to prevent asthma and its exacerbation.

PMID- 29338156
TI  - Attenuating Effect of Long-term Culture of Umbilical Cord Vein Mesenchymal
      Stromal Cells on Pulmonary Fibrosis in C57BL/6 Mice.
AB  - In recent studies, mesenchymal stromal cells (MSCs) have been increasingly
      employed to treat various diseases like pulmonary fibrosis (PF). There are very
      few MSCs in tissues so in order to obtain their sufficient numbers for
      therapeutic applications, their in vitro expansion is necessary. The aim of this
      study was to investigate the effects of long-term culture of the human umbilical
      cord vein MSCs (hUCV-MSCs) on pulmonary fibrosis in mice. MSCs were first
      isolated from human umbilical cord vein and cultured up to 18 passages. In
      C57BL/6 mice, 15 min after belomycin instillation, UCV-MSCs at passages (P) 0, 4,
      8, 12, and 18 (long-term culture) were transplanted intratracheally. Mice were
      weighted every 5 days and were euthanized on day 21. For histopathological
      examination, the lung sections were stained with hematoxylin-eosin (HE) and
      Masson's trichrome. The mRNA expression of TGF-beta1, alpha-smooth muscle actin
      (alpha-SMA), and collagen type I alpha 1 (COL1A1) in lung tissues were assessed
      using RT-PCR. For cell tracking, human cytochrome B DNA was detected in mice lung
      tissues by PCR. The weight of mice receiving long-term culture of UCV-MSCs
      increased compared to other mice (p=0.056). Also, transplantation of UCV-MSCs at
      P18 led to increased alveolar space and decreased connective tissue and collagen
      deposition of the lung tissues. The mRNA expression of TGF-beta1, alpha-SMA, and
      COL1A1 also decreased in this group. The results showed that intratracheally
      transplanted long-term culture of the UCV-MSCs attenuated lung fibrosis in mice.

PMID- 29338157
TI  - Imbalance of Th17/Treg in the Pathogenesis of Mice with Paraquat-induced Acute
      Lung Injury.
AB  - Recent studies suggest that imbalances in the ratios of CD4+ T helper cell
      subsets, T helper-17 (Th17) and regulatory T (Treg) cells play a crucial role in
      the pathogenesis of acute lung injury (ALI). However, studies of the imbalance of
      Th17/Treg in paraquat (PQ)-induced ALI have not been reported. Therefore, we
      investigated whether the ratio of Th17/Treg cells in a mouse model of PQ-induced
      ALI contributes to pathogenesis of ALI. Male Kunming mice were randomly treated
      with saline (control group) or PQ (PQ-poisoned (PQP) group); mice were sacrificed
      at either 12 hours (PQP-12h) or 24 hours (PQP-24h and control) post-treatment.
      Hematoxylin-eosin and TUNEL staining procedures were performed to examine
      inflammation and apoptosis. The presence of Th17 and Treg cells was measured by
      flow cytometry; the expression of putative Th17 cytokines and transcription
      factors was measured by ELISA and western blot analysis. Compared with control
      mice, lung inflammation and apoptosis were dramatically increased in PQP mice at
      12 and 24 hours after poisoning. In addition, poisoned mice displayed significant
      increases in the presence of CD4+IL-17+ T cells (Th17) and in the expression of
      IL-17A and IL-17, as measured by flow cytometry and western blot assays. This
      increase was most notable after 24 hours of PQ exposure. Furthermore, poisoned
      mice displayed marked decreases in the presence of CD4+CD25+Foxp3+ T cells (Treg)
      and in the expression of IL-35 and the transcription factor Foxp3. These results
      suggest that an imbalanced ratio of Th17/Treg cells may contribute to the
      pathogenesis of PQ-induced ALI.

PMID- 29338158
TI  - Studying the Serum as Well as Serous Level of IL-17 and IL-23 in Patients with
      Serous Otitis Media.
AB  - Serous otitis media with effusion (OME) is a middle ear inflammatory response to
      allergens and microbes which stimulate leukocytes to produce different
      inflammatory mediators after obstruction of Eustachian tube. Here, we
      investigated the levels of these mediators, IL-17 and IL-23, in serum and middle
      ear fluids of children with OME. 75 patients with otitis media and 75 age and sex
      matched healthy controls were enrolled in this study. IL-17 and IL-23 levels in
      serous secretion of the patients and their serum levels were measured in both
      groups by ELISA. Serum IL-17 levels were significantly higher in the patients
      than controls (p=0.001). There was no significant difference between serum IL-23
      levels in patients and controls. Patients' serous levels of both cytokines of IL
      17 and IL-23 were higher than those in serum according to different parameters of
      sex, age, and duration of the disease. This study shows an elevated presence of
      IL-17 and IL-23, as pro inflammatory cytokines, in OME. These finding may
      represent the contribution of such cytokines in the pathogenesis of OME. Blocking
      such molecules may yield new non-surgical therapeutics.

PMID- 29338159
TI  - Ovariectomy Modifies TH2, and TH17 Balance in BALB/C Allergic Mice.
AB  - Asthma is a chronic inflammation of the airways affecting over 300 million people
      worldwide. As in the autoimmune diseases, it is well described that women are the
      most affected by asthma. The higher number of women presenting this pathology
      suggests the involvement of female sex hormones in the construction of the
      allergic immune response. Female Balb / c mice were used for the experiments.
      Thirty-eight animals were separated into four groups: OVX-Ova; Sham-Ova; OVX-Sal;
      Sham-Sal. Then animals underwent acute allergic induction protocol by Ovalbulmin
      (OVA). Ovariectomized animals showed greater number of leukocytes in
      bronchoalveolar lavage (BAL) and elevated white blood cells recruitment to the
      lung environment observed by histological analysis. There was a significant
      increase of eosinophils and mast cells in inflammatory sites at pulmonary tissue.
      The relative uterine and body weight were lower in ovariectomized animals and
      higher in Sham mice, respectively. Moreover, the lack of the sex hormones induced
      an increase in interleukin (IL)-4 and titers of immunoglobulin G1 (IgG1)
      antibodies. However, increased production of IL-17A was only observed in Sham
      animals. Altogether, data this study suggest that ovariectomy induces the
      formation of a stronger Th2 response in allergic animal. However, the immune
      processes involved in the allergic response in females currently remain unclear.

PMID- 29338160
TI  - Higher Activities of Hepatic Versus Splenic CD8+ T Cells in Responses to Adoptive
      T Cell Therapy and Vaccination of B6 Mice with MHC Class-1 Binding Antigen.
AB  - The liver has unique microenvironment which is known to induce tolerance of
      cytolytic CD8+ T cells to hepatic and extra hepatic antigens, resulting in
      persistence of infection of the liver by the hepatitis B and C viruses. However,
      under some conditions, functional immune responses can be elicited in the liver
      in particular to show preferential retention of activated CD8+ T cells. It is not
      clear whether this retention depends on the type of the exogenous
      immunostimulatory or the endogenous innate immune cells. The T cell receptor
      (TCR) transgenic OT-1 (CD8+) mouse model was used in which OT-1 cells were
      harvested from the spleen of the donor and transferred into recipient mice
      followed by immunization with OVA peptide followed by injection of GM-CSF, CCL21
      chemokine, or cytokines (IL-2, IL-12, or IL-15), or the toll-like receptor 3
      agonist poly(I:C). Co-administration of any of these immunostimulatory agents
      relatively augmented the retention of CD8+ T cells with different levels of
      effects. Compared to spleen, the Ag-specific CD8+ T cells in the liver showed
      higher activities including expansion, proliferation, apoptosis and memory
      responses as well as cytolytic function. While depletion of natural killer cells
      significantly decreased the hepatic retention of the antigen-specific T cells,
      depletion of Kupffer cells showed opposite effect. Taken together, the antigen
      reactive T cells in the liver have higher activities than their counterparts in
      the peripheral tissues such as spleen. These data have important clinical
      implications for designing immunotherapeutic protocols toward the liver diseases.

PMID- 29338161
TI  - Effect of Periodontal Treatment on the Crevicular Level of High-mobility Group
      Box 1 and Soluble Triggering Receptor Expressed on Myeloid Cells 1 in Patients
      with Chronic Periodontitis.
AB  - The present study aimed to compare the levels of high-mobility group box 1(HMGB1)
      and soluble triggering receptor expressed on myeloid cells (sTREM1) in the
      gingival crevicular fluid (GCF). This cross-sectional cohort trial investigated
      two groups of 22 eligible chronic periodontitis and 22 periodontally healthy
      individuals (student volunteers) both before and after the periodontal treatment.
      GCF was collected from the deepest pockets with clinical attachment loss>=3 mm.
      Both groups received oral hygiene instructions, and scaling and root planning
      were performed in the test group. Enzyme-linked immunosorbent assay kit (ELISA)
      was used to measure the levels of HMGB1 and sTREM1 in GCF samples collected
      before and 1 month after non-surgical periodontal treatment. The results showed
      that HMGB1 levels were significantly higher in the chronic periodontitis patients
      than those of the healthy individuals before treatment (p<0.02) and decreased
      significantly after periodontal treatment, which reduced gingival inflammation.
      Furthermore, the levels of sTREM1 marker were significantly higher in
      periodontitis patients before (p<0.001) and 1 month after treatment than in
      healthy individuals (p<0.003) although its crevicular levels decreased after
      periodontal therapy in periodontitis group. The higher levels of sTREM1 and HMGB1
      cytokines in GCF of periodontitis patients and the significant decrease after the
      introduction of the periodontal treatment underlines the importance of HMGB1 and
      sTREM1 in pathogenesis of periodontitis.

PMID- 29338162
TI  - Endobronchial Lesion in Eosinophilic Granulomatosis with Polyangiitis.
AB  - Eosinophilic granulomatosis with polyangiitis is a systemic vasculitis. It could
      affect respiratory system, kidney, and central nervous system frequently;
      however, all body organs could be involved. Asthma and eosinophilic pneumonia are
      predominant manifestations in respiratory system. Bronchoalveolar lavage or lung
      biopsy may be used for diagnosis, but endobronchial lesion is not considered as a
      manifestation of eosinophilic granulomatosis with polyangiitis. Here we present a
      case of eosinophilic granulomatosis with polyangiitis with unusual endobronchial
      lesion which was confirmed by endobronchial biopsy.

PMID- 29338163
TI  - Kounis Syndrome Induced by Oral Intake of Diclofenac Potassium.
AB  - An acute coronary syndrome (ACS) occurring during the course of an allergic
      reaction is called Kounis syndrome (KS). The second case of KS induced by
      diclofenac potassium (DP) is presented in this report. A 67-year-old man was
      brought to our emergency department with the possible diagnosis of anaphylactic
      shock by the ambulance staff. It emerged that widespread erythema and pruritus
      developed after taking DP. Then, he lost consciousness. Diffuse urticarial
      lesions were detected on physical examination at the emergency department. He
      complained of chest pain during his observation, and progressive ST segment
      elevation was seen in the inferior leads on serial electrocardiograms. His
      coronary angiography showed 100% occlusion of the right coronary artery.  Then,
      KS was diagnosed. The patient was discharged on the second day, and he was doing
      well on the control visit 2 weeks later. All allergic reactions may trigger an
      ACS so physicians should be aware of KS and always keep that unique clinical
      entity in mind to recognize it promptly and direct the therapy at suppressing the
      allergic reaction and improving the coronary circulation simultaneously when
      encountering a patient with symptoms suggesting an allergic reaction and a
      concomitant ACS.

PMID- 29338164
TI  - The relation between nonspecific hyperreactivity of the airways and atopic
      constitution in asthmatics.
AB  - Background/Aim: Hyperreactivity of the airways caused by inflammation in
      asthmatics is the most important pathophysiological change. It represents a
      suitable ground that in the presence of risk factors and the drivers of asthma,
      asthmatic attack occurs. Atopic constitution is one of the most important risk
      factors for the development and expression of asthma. The aim of our study was to
      investigate the relationship between nonspecific airway hyperreactivity and
      atopic constituton in asthmatics. Methods: This retrospective analysis was
      conducted considering the results of nonspecific bronchoprovocative test with
      histamine, skin tests to inhalant allergens and total IgE levels in the serum of
      asthmatic patients with controlled bronchial asthma. The sample consisted of 162
      asthmatics examined during one-year period. Results: The examinees were male
      asthmatic patients, aged between 18 and 30 years. We found that the examinees
      with a pronounced non-specific hyperreactivity had more significant skin reaction
      to inhaled allergens and higher levels of total IgE in serum. Conclusion: The
      results of our study show that the intensity of airway hyperresponsiveness to
      histamine in asthmatics is directly related to atopic constitution.

PMID- 29338165
TI  - How Ligands Affect Resistive Switching in Solution-Processed HfO2 Nanoparticle
      Assemblies.
AB  - Advancement of resistive random access memory (ReRAM) requires fully
      understanding the various complex, defect-mediated transport mechanisms to
      further improve performance. Although thin-film oxide materials have been
      extensively studied, the switching properties of nanoparticle assemblies remain
      underexplored due to difficulties in fabricating ordered structures. Here, we
      employ a simple flow coating method for the facile deposition of highly ordered
      HfO2 nanoparticle nanoribbon assemblies. The resistive switching character of
      nanoribbons was determined to correlate directly with the organic capping layer
      length of their constituting HfO2 nanoparticles, using oleic acid, dodecanoic
      acid, and undecenoic acid as model nanoparticle ligands. Through a systematic
      comparison of the forming process, operating set/reset voltages, and resistance
      states, we demonstrate a tunable resistive switching response by varying the
      ligand type, thus providing a base correlation for solution-processed ReRAM
      device fabrication.

PMID- 29338166
TI  - Remarkable Effect of Sodium Alginate Aqueous Binder on Anatase TiO2 as High
      Performance Anode in Sodium Ion Batteries.
AB  - Sodium alginate (SA) is investigated as the aqueous binder to fabricate high
      performance, low-cost, environmentally friendly, and durable TiO2 anodes in
      sodium-ion batteries (SIBs) for the first time. Compared to the conventional
      polyvinylidene difluoride (PVDF) binder, electrodes using SA as the binder
      exhibit significant promotion of electrochemical performances. The initial
      Coulombic efficiency is as high as 62% at 0.1 C. A remarkable capacity of 180 mAh
      g-1 is achieved with no decay after 500 cycles at 1 C. Even at 10 C (3.4 A g-1),
      it remains 82 mAh g-1 after 3600 cycles with approximate 100% Coulombic
      efficiency. TiO2 electrodes with SA binder display less electrolyte
      decomposition, fewer side reactions, high electrochemistry reaction activity,
      effective suppression of polarization, and good electrode morphology, which is
      ascribed to the rich carboxylic groups, high Young's modulus, and good
      electrochemical stability of SA binder.

PMID- 29338167
TI  - Nitrogen-Doped Perovskite as a Bifunctional Cathode Catalyst for Rechargeable
      Lithium-Oxygen Batteries.
AB  - In this work, nitrogen-doped LaNiO3 perovskite was prepared and studied, for the
      first time, as a bifunctional electrocatalyst for oxygen cathode in a
      rechargeable lithium-oxygen battery. N doping was found to significantly increase
      the Ni3+ contents and oxygen vacancies on the bulk surface of the perovskite,
      which helped to promote the oxygen reduction reaction and oxygen evolution
      reaction of the cathode and, therefore, enabled reversible Li2O2 formation and
      decomposition on the cathode surface. As a result, the oxygen cathodes loaded
      with N-doped LaNiO3 catalyst showed an improved electrochemical performance in
      terms of discharge capacity and cycling stability to promise practical Li-O2
      batteries.

PMID- 29338168
TI  - Nanocapsules of Magnetic Au Self-Assembly for DNA Migration and Secondary Self
      Assembly.
AB  - To endow valuable responsiveness to self-assemblies of Au nanoparticles (Au NPs),
      the magnetic Au nanoparticles (Au NPs)/C16H33(CH3)3N+[CeCl3Br]- (CTACe) mixtures
      were first prepared by using an emulsion self-assembly of a magnetic surfactant,
      C16H33(CH3)3N+[CeCl3Br]-. A versatile morphology of self-assemblies of Au NPs
      could be controlled by the counterions in surfactants including [CeCl3Br]-,
      [FeCl3Br]-, and Br- as well as solvent. In particular, the magnetic counterion,
      [CeCl3Br]-, can induce self-growth of Au NPs in an emulsion self-assembly process
      due to the oxidability of [CeCl3Br]-. It enhances the rigidity of Au NPs/CTACe
      scaffolds template compared with Au NPs/hexadecyltrimethylammonium bromide.
      [CeCl3Br]- engaged Au NPs/CTACe with fascinating capability of conglutination and
      targeted migration of DNA (150 MUmol/L) under a magnet field. The conglutination
      capability of the DNA molecules can increase to 39.8% by adopting the magnetic
      strategy when using Au NPs/CTACe as a magnetic booster. Au NPs/CTACe mixtures can
      ideally self-assemble to be scaffolds, providing abundant conjugation sites of
      surface charges. Magnetic Au NPs/CTACe can serve as a template scaffold to
      secondary self-assemble with DNA (40 mmol/L) outside, producing smooth-faced and
      hollow DNA nanocapsules. We believe that the creative Au NPs/CTACe/DNA
      nanocapsules will extend the biological application field of Au NPs assemblies.

PMID- 29338169
TI  - Highly Efficient Soluble Blue Delayed Fluorescent and Hyperfluorescent Organic
      Light-Emitting Diodes by Host Engineering.
AB  - Solution-processed high-efficiency fluorescent organic light-emitting diodes with
      an external quantum efficiency over 18% were developed by engineering a host
      material and device structure designed for solution process. A high triplet
      energy host material designed for the solution process, (oxybis(3-(tert-butyl)
      6,1-phenylene))bis(diphenylphosphine oxide) (DPOBBPE), worked efficiently as the
      host of blue fluorescent devices because of good solubility, high
      photoluminescence quantum yield, and good film properties. The DPOBBPE host
      enabled a high external quantum efficiency of 18.8% in the fluorescent organic
      light-emitting diodes by the solution process. Moreover, 25.8% external quantum
      efficiency in the soluble blue thermally activated delayed fluorescent devices
      was also realized. The 25.8% external quantum efficiency of the DPOBBPE delayed
      fluorescent device and 18.8% external quantum efficiency of the fluorescent
      device are the highest efficiency values achieved in the solution-processed blue
      fluorescent organic light-emitting diodes. Moreover, the solution-processed
      fluorescent device showed an improved blue color coordinate of (0.14, 0.20)
      compared to (0.17, 0.31) of the delayed fluorescent device.

PMID- 29338170
TI  - PEALD of SiO2 and Al2O3 Thin Films on Polypropylene: Investigations of the Film
      Growth at the Interface, Stress, and Gas Barrier Properties of Dyads.
AB  - A study on the plasma-enhanced atomic layer deposition of amorphous inorganic
      oxides SiO2 and Al2O3 on polypropylene (PP) was carried out with respect to
      growth taking place at the interface of the polymer substrate and the thin film
      employing in situ quartz-crystal microbalance (QCM) experiments. A model layer of
      spin-coated PP (scPP) was deposited on QCM crystals prior to depositions to allow
      a transfer of findings from QCM studies to industrially applied PP foil. The
      influence of precursor choice (trimethylaluminum (TMA) vs [3
      (dimethylamino)propyl]-dimethyl aluminum (DMAD)) and of plasma pretreatment on
      the monitored QCM response was investigated. Furthermore, dyads of SiO2/Al2O3,
      using different Al precursors for the Al2O3 thin-film deposition, were
      investigated regarding their barrier performance. Although the growth of SiO2 and
      Al2O3 from TMA on scPP is significantly hindered if no oxygen plasma pretreatment
      is applied to the scPP prior to depositions, the DMAD process was found to yield
      comparable Al2O3 growth directly on scPP similar to that found on a bare QCM
      crystal. From this, the interface formed between the Al2O3 and the PP substrate
      is suggested to be different for the two precursors TMA and DMAD due to different
      growth modes. Furthermore, the residual stress of the thin films influences the
      barrier properties of SiO2/Al2O3 dyads. Dyads composed of 5 nm Al2O3 (DMAD) + 5
      nm SiO2 exhibit an oxygen transmission rate (OTR) of 57.4 cm3 m-2 day-1, which
      correlates with a barrier improvement factor of 24 against 5 when Al2O3 from TMA
      is applied.

PMID- 29338171
TI  - Flexible Capacitive Piezoelectric Sensor with Vertically Aligned Ultralong GaN
      Wires.
AB  - We report a simple and scalable fabrication process of flexible capacitive
      piezoelectric sensors using vertically aligned gallium nitride (GaN) wires as
      well as their physical principles of operation. The as-grown N-polar GaN wires
      obtained by self-catalyst metal-organic vapor phase epitaxy are embedded into a
      polydimethylsiloxane (PDMS) matrix and directly peeled off from the sapphire
      substrate before metallic electrode contacting. This geometry provides an
      efficient control of the wire orientation and an additive contribution of the
      individual piezoelectric signals. The device output voltage and efficiency are
      studied by finite element calculations for compression mechanical loading as a
      function of the wire geometrical growth parameters (length and density). We
      demonstrate that the voltage output level and sensitivity increases as a function
      of the wire length and that a conical shape is not mandatory for potential
      generation as it was the case for horizontally assembled devices. The optimal
      design to improve the overall device response is also optimized in terms of wire
      positioning inside PDMS, wire density, and total device thickness. Following the
      results of these calculations, we have fabricated experimental devices exhibiting
      outputs of several volts with a very good reliability under cyclic mechanical
      excitation.

PMID- 29338172
TI  - Activation of Nrf2 and Hypoxic Adaptive Response Contribute to Neuroprotection
      Elicited by Phenylhydroxamic Acid Selective HDAC6 Inhibitors.
AB  - Activation of HIF-1alpha and Nrf2 is a primary component of cellular response to
      oxidative stress, and activation of HIF-1alpha and Nrf2 provides neuroprotection
      in models of neurodegenerative disorders, including ischemic stroke, Alzheimer's
      and Parkinson's diseases. Screening a library of CNS-targeted drugs using novel
      reporters for HIF-1alpha and Nrf2 elevation in neuronal cells revealed histone
      deacetylase (HDAC) inhibitors as potential activators of these pathways. We
      report the identification of phenylhydroxamates as single agents exhibiting
      tripartite inhibition of HDAC6, inhibition of HIF-1 prolyl hydroxylase (PHD), and
      activation of Nrf2. Two superior tripartite agents, ING-6 and ING-66, showed
      neuroprotection against various cellular insults, associated with stabilization
      of both Nrf2 and HIF-1, and expression of their respective target genes in vitro
      and in vivo. Discovery of the innate ability of phenylhydroxamate HDAC inhibitors
      to activate Nrf2 and HIF provides a novel route to multifunctional
      neuroprotective agents and cautions against HDAC6 selective inhibitors as
      chemical probes of specific HDAC isoform function.

PMID- 29338173
TI  - Smartphone-Based VOC Sensor Using Colorimetric Polydiacetylenes.
AB  - Owing to a unique colorimetric (typically blue-to-red) feature upon environmental
      stimulation, polydiacetylenes (PDAs) have been actively employed in chemosensor
      systems. We developed a highly accurate and simple volatile organic compound
      (VOC) sensor system that can be operated using a conventional smartphone. The
      procedure begins with forming an array of four different PDAs on conventional
      paper using inkjet printing of four corresponding diacetylenes followed by
      photopolymerization. A database of color changes (i.e., red and hue values) is
      then constructed on the basis of different solvatochromic responses of the 4 PDAs
      to 11 organic solvents. Exposure of the PDA array to an unknown solvent promotes
      color changes, which are imaged using a smartphone camera and analyzed using the
      app. A comparison of the color changes to the database promoted by the 11
      solvents enables the smartphone app to identify the unknown solvent with 100%
      accuracy. Additionally, it was demonstrated that the PDA array sensor was
      sufficiently sensitive to accurately detect the 11 VOC gases.

PMID- 29338174
TI  - Solution-Processable ZnO/Carbon Quantum Dots Electron Extraction Layer for Highly
      Efficient Polymer Solar Cells.
AB  - In this work, we report the effort to develop high-efficiency inverted polymer
      solar cells (PSCs) by applying a solution-processable bilayer ZnO/carbon quantum
      dots (C-QDs) electron extraction layer (EEL). It is shown that the use of the
      bilayer EEL helps to suppress the exciton quenching by passivating the ZnO
      surface defects in the EEL, leading to an enhanced exciton dissociation, reduced
      charge recombination and more efficient charge extraction probability, and
      thereby achieving high power conversion efficiency (PCE). The inverted PSCs,
      based on the blend of poly{4,8-bis[(2-ethylhexyl)oxy]benzo[1,2-b:4,5
      b']dithiophene-2,6-diyl-alt-3-fluoro-2-[(2-ethylhexyl)carbonyl]thieno[3,4
      b]thiophene-4,6-diyl} and [6,6]-phenyl C71-butyric acid methyl ester, possess a
      significant improvement in PCE of ~9.64%, which is >27% higher than that of a
      control cell (~7.59%). The use of a bilayer ZnO/C-QD EEL offers a promising
      approach for attaining high-efficiency inverted PSCs.

PMID- 29338175
TI  - Limitations of Cs3Bi2I9 as Lead-Free Photovoltaic Absorber Materials.
AB  - Lead (Pb) halide perovskites have attracted tremendous attention in recent years
      because of their rich optoelectronic properties, which have resulted in more than
      22% power conversion efficient photovoltaics (PVs). Nevertheless, Pb-metal
      toxicity remains a huge hurdle for extensive applications of these compounds.
      Thus, alternative compounds with similar optoelectronic properties need to be
      developed. Bismuth possesses electronic structure similar to that of lead with
      the presence of ns2 electrons that exhibit rich structural variety as well as
      interesting optical and electronic properties. Herein, we critically assess
      Cs3Bi2I9 as a candidate for thin-film solar cell absorber. Despite a reasonable
      optical band gap (~2 eV) and absorption coefficient, the power conversion
      efficiency of the Cs3Bi2I9 mesoscopic solar cells was found to be severely
      lacking, limited by the poor photocurrent density. The efficiency of the Cs3Bi2I9
      solar cell can be slightly improved by changing the stoichiometry of the
      precursor solutions, which is most probably due to the reduction in nonradiative
      defects as evident from our single-crystal photoluminescence spectroscopy.
      However, detailed investigations on pristine Cs3Bi2I9 reveal that zero
      dimensional molecular crystal structure remains one of the main bottlenecks in
      achieving high performance. On the basis of our comprehensive studies, we have
      proposed that a continuous network of three-dimensional crystal structure should
      be another major criterion in addition to proper band gap and suitable optical
      properties of the future PV compounds.

PMID- 29338176
TI  - Polystyrene-block-Poly(ionic liquid) Copolymers as Work Function Modifiers in
      Inverted Organic Photovoltaic Cells.
AB  - Interfacial layers play a critical role in building up the Ohmic contact between
      electrodes and functional layers in organic photovoltaic (OPV) solar cells. These
      layers are based on either inorganic oxides (ZnO and TiO2) or water-soluble
      organic polymers such as poly[(9,9-dioctyl-2,7-fluorene)-alt-(9,9-bis(3'-(N,N
      dimethylamino)propyl)-2,7-fluorene)] and polyethylenimine ethoxylated (PEIE). In
      this work, we have developed a series of novel poly(ionic liquid) nonconjugated
      block copolymers for improving the performance of inverted OPV cells by using
      them as work function modifiers of the indium tin oxide (ITO) cathode. Four
      nonconjugated polyelectrolytes (n-CPEs) based on polystyrene and imidazolium
      poly(ionic liquid) (PSImCl) were synthesized by reversible addition-fragmentation
      chain transfer polymerization. The ratio of hydrophobic/hydrophilic block
      copolymers was varied depending on the ratio of polystyrene to the PSImCl block.
      The ionic density, which controls the work function of the electrode by forming
      an interfacial dipole between the electrode and the block copolymers, was easily
      tuned by simply changing the PSImCl molar ratio. The inverted OPV device with the
      ITO/PS29-b-PSImCl60 cathode achieved the best power conversion efficiency (PCE)
      of 7.55% among the synthesized block copolymers, exhibiting an even higher PCE
      than that of the reference OPV device with PEIE (7.30%). Furthermore, the surface
      properties of the block copolymers films were investigated by contact angle
      measurements to explore the influence of the controlled hydrophobic/hydrophilic
      characters on the device performances.

PMID- 29338177
TI  - Novel Alkali Activation of Titanium Substrates To Grow Thick and Covalently Bound
      PMMA Layers.
AB  - Titanium (Ti) is the most widely used metal in biomedical applications because of
      its biocompatibility; however, the significant difference in the mechanical
      properties between Ti and the surrounding tissues results in stress shielding
      which is detrimental for load-bearing tissues. In the current study, to attenuate
      the stress shielding effect, a new processing route was developed. It aimed at
      growing thick poly(methyl methacrylate) (PMMA) layers grafted on Ti substrates to
      incorporate a polymer component on Ti implants. However, the currently available
      methods do not allow the development of thick polymeric layers, reducing
      significantly their potential uses. The proposed route consists of an alkali
      activation of Ti substrates followed by a surface-initiated atom transfer radical
      polymerization using a phosphonic acid derivative as a coupling agent and a
      polymerization initiator and malononitrile as a polymerization activator. The
      average thickness of the grown PMMA layers is approximately 1.9 MUm. The Ti
      activation-performed in a NaOH solution-leads to a porous sodium titanate
      interlayer with a hierarchical structure and an open microporosity. It promotes
      the covalent grafting reaction because of high hydroxyl groups' content and
      enables establishing a further mechanical interlocking between the growing PMMA
      layer and the Ti substrate. As a result, the produced graduated structure
      possesses high Ti/PMMA adhesion strength (~260 MPa). Moreover, the PMMA layer is
      (i) thicker compared to those obtained with the previously reported techniques
      (~1.9 MUm), (ii) stable in a simulated body fluid solution, and (iii)
      biocompatible. This strategy opens new opportunities toward hybrid prosthesis
      with adjustable mechanical properties with respect to host bone properties for
      personalized medicines.

PMID- 29338178
TI  - DNA Damage and Apoptosis Induction in Cancer Cells by Chemically Engineered
      Thiolated Riboflavin Gold Nanoassembly.
AB  - Herein we have engineered a smart nuclear targeting thiol-modified riboflavin
      gold nano assembly, RfS@AuNPs, which accumulates selectively in the nucleus
      without any nuclear-targeting peptides (NLS/RGD) and shows photophysically in
      vitro DNA intercalation. A theoretical model using Molecular Dynamics has been
      developed to probe the mechanism of formation and stability as well as dynamics
      of the RfS@AuNPs in aqueous solution and within the DNA microenvironment. The
      RfS@AuNPs facilitate the binucleated cell formation that is reflected in the
      significant increase of DNA damage marker, gamma-H2AX as well as the arrest of
      most of the HeLa cells at the pre-G1 phase indicating cell death. Moreover, a
      significant upregulation of apoptotic markers confirms that the cell death occurs
      through the apoptotic pathway. Analyses of the microarray gene expression of
      RfS@AuNPs treated HeLa cells show significant alterations in vital biological
      processes necessary for cell survival. Taken together, our study reports a unique
      nuclear targeting mechanism through targeting the riboflavin receptors, which are
      upregulated in cancer cells and induce apoptosis in the targeted cells.

PMID- 29338179
TI  - Ligand-Switchable Micellar Nanocarriers for Prolonging Circulation Time and
      Enhancing Targeting Efficiency.
AB  - Targeted drug delivery of nanomedicines offered a promising strategy to improve
      the tumor accumulation and reduce the side effects of chemotherapeutics. However,
      undesired recognition of the targeting ligands on the surface of nanocarriers by
      immune systems or normal tissues decreased the circulation time and reduced the
      targeting efficiency. Here, we developed a ligand-switchable micellar nanocarrier
      that can hide the targeting ligands when circulating in the bloodstream and
      expose them on the surface when entering the tumor microenvironments. With the
      ligand-switching capability, the nanocarrier achieved a 66% longer blood
      circulation half-life and a 23% higher tumor accumulation than the nanocarrier
      with targeting ligands on the surface. This targeting strategy could serve as a
      universal approach to improve the targeting efficiency for nanomedicines.

PMID- 29338180
TI  - Hollow Echinus-like PdCuCo Alloy for Superior Efficient Catalysis of Ethanol.
AB  - Large-scale preparation of hollow echinus-like PdCuCo alloy nanostructures
      (HENSs) with a high surface area-to-volume ratio, rich active sites, and
      relatively efficient catalytic activity has attracted considerable research
      interest. Herein, we present an economic and facile approach to synthesize HENSs
      by galvanic exchange reactions using Co nanospheres as sacrificial templates.
      Moreover, the catalytic activity could be adjusted via changing the composition
      of the catalyst. The composition, morphology, and crystal structure of the as
      obtained nanomaterials are characterized by various techniques, such as
      inductively coupled plasma atomic emission spectrometry, transmission electron
      microscopy, and X-ray diffraction. Electrochemical catalytic measurement results
      prove that the Pd75Cu8Co3 catalyst obtained under optimal preparation conditions
      exhibits 10-fold higher activity for ethanol oxidation in comparison with the
      commercially available 20% Pd/C catalyst. The eminent performance of the
      Pd75Cu8Co3 electrochemical catalyst could be ascribed to the peculiar echinus
      like nanostructures.

PMID- 29338181
TI  - Attaining Melt Processing of Complementary Semiconducting Polymer Blends at 130 
      degrees C via Side-Chain Engineering.
AB  - Complementary semiconducting polymer blends (c-SPBs) have been proposed and
      tested to achieve melt-processed high-performance organic field-effect
      transistors (OFETs). Prior to this study, melt processing requires temperatures
      as high as 180  degrees C. To implement this technique into low-cost and large
      area thin-film manufacturing for flexible organic electronics, semiconducting
      materials meltable at temperatures tolerable by ubiquitous plastic substrates are
      still needed. We report here the design and melt processing of a c-SPB consisting
      of a matrix polymer (DPP-C5) and its fully conjugated analogue. By utilizing a
      siloxane-terminated alkyl chain and a branched alkyl chain as solubilizing
      groups, the matrix polymer DPP-C5 presents a melting temperature of 115  degrees
      C. The resulting c-SPB containing as low as 5% of the fully conjugated polymer
      could be melt-processed at 130  degrees C. The obtained OFET devices exhibit hole
      mobility approaching 1.0 cm2/(V s), threshold voltages below 5 V, and ION/IOFF
      around 105. This combination of efficient charge-carrier transport and
      considerably low processing temperatures bode well for melt processing of
      semiconducting polymer-based organic electronics.

PMID- 29338182
TI  - "Infinite Sensitivity" of Black Silicon Ammonia Sensor Achieved by Optical and
      Electric Dual Drives.
AB  - The microstructured and hyperdoped silicon as a superior photoelectric and
      photovoltaic material is first studied as a gas-sensing material. The material is
      prepared by femtosecond-laser irradiation on selenium-coated silicon and then
      fabricated as a conductive gas sensor, targeting ammonia. At room temperature,
      the sensitivity, response time, repeatability, distinguishability, selectivity,
      and natural aging effect of the sensor have been systematically studied. Results
      show that such black silicon has good potential for application as an ammonia
      sensing material. On the basis of its unique optoelectronic properties, an
      additional optical drive is proposed for the formation of an optical and electric
      dual-driven sensor, which is achieved by asymmetric light illumination between
      the two electrode regions. In a certain range of applied voltage, the sensitivity
      is enhanced dramatically and even tends to be infinite. For the aged device with
      degraded sensitivity, a two-order increment is obtained for 500 ppm of NH3 under
      the extra optical drive. A mechanism based on Dember effect is proposed for
      explaining such a phenomenon.

PMID- 29338183
TI  - Plasma-Induced Oxygen Vacancies in Urchin-Like Anatase Titania Coated by Carbon
      for Excellent Sodium-Ion Battery Anodes.
AB  - The incorporation of oxygen vacancies in anatase TiO2 has been studied as a
      promising way to accelerate the transport of electrons and Na+ ions, which is
      important for achieving excellent electrochemical properties for anatase TiO2.
      However, wittingly introducing oxygen vacancies in anatase TiO2 for sodium-ion
      anodes by a facile and effective method is still a challenge. In this work, we
      report an innovative method to introduce oxygen vacancies into the urchin-like N
      doped carbon coated anatase TiO2 (NC-DTO) by a facile plasma treatment. The
      superiorities of the oxygen vacancies combined with the conductive N-doped carbon
      coating enable the obtained NC-DTO of greatly improved sodium storage
      performance. When served as the anode for sodium-ion batteries, the NC-DTO
      electrode shows superior electrochemical performance (capacity: 272 mA h g-1 at
      0.25 C, capacity retention: 98.8% after 5000 cycles at 10 C, as well as ultrahigh
      capacity: 150 mA h g-1 at 15 C). Density functional theory calculations combined
      with experimental results suggest that considerably improved sodium storage
      performance of NC-DTO is due to the enhanced electronic conductivity from the N
      doped carbon layer as well as narrowed band gap and lowered sodiation energy
      barrier from the introduction of oxygen vacancies. This work highlights that
      introducing oxygen vacancies into TiO2 by plasma is a promising method to enhance
      the electrochemical property of TiO2, which also can be applied to different
      metal oxides for energy storage devices.

PMID- 29338184
TI  - Design of pH-Sensitive Nanovesicles via Cholesterol Analogue Incorporation for
      Improving in Vivo Delivery of Chemotherapeutics.
AB  - pH-responsive polymersomes have emerged as promising nanocarriers for antitumor
      drugs to realize their fast release and action in a weakly acidic
      microenvironment of tumor cells. Herein, however, we designed a remarkably pH
      responsive polymersome self-assembled from amphiphilic benzimidazole-based
      polyphosphazenes via the incorporation of cholesteryl hemisuccinate (CholHS), a
      type of cholesteric molecule, into the polymersome bilayers to inhibit the drug
      release during blood circulation. Actually, unwanted premature drug leakage
      before arriving at the acidic tumor site has become a serious problem for
      polymersomes encapsulating water-soluble drugs, especially when the drug loading
      is at a high level, thus limiting the therapeutic efficacy. In this study,
      polymersomes displayed high loading capability of doxorubicin hydrochloride as
      12.83%. More importantly, CholHS incorporation decreased the membrane
      permeability of the polymersome and effectively retarded the cargo release under
      physiological conditions but induced the fast drug-release rate at pH 5.5,
      demonstrating a more remarkably acid-responsive release behavior when compared to
      that of the CholHS-free polymersomes. Further in vivo investigations including
      pharmacokinetic and antitumor activity studies verified the extended circulation
      time and enhanced antitumor efficacy of the drug-loaded CholHS-incorporated
      polymersomes.

PMID- 29338185
TI  - Injectable and Thermosensitive Hydrogel and PDLLA Electrospun Nanofiber Membrane
      Composites for Guided Spinal Fusion.
AB  - Spinal fusion is the classic treatment to achieve spinal stability for the
      treatment of the spinal disease. Generally, spinal fusion still has to combine a
      certain of bone matrix for promoting bone formation to achieve the desired fusion
      effect based on the surgery, including the traditional bone matrix, such as the
      autologous bone, allografts and xenografts. Nevertheless, some problems still
      existed such as the immunogenic problems, the secondary wound, and pathogenic
      transfer and so on. Here the injectable thermosensitive hydrogel could substitute
      to avoid the problems as a potential biological scaffold for tissue engineering.
      Once injected, they could fill in the irregular-shaped cavity and change to a gel
      state at physiological temperature. We wanted to design the collagen/n-HA/BMP
      2@PCEC/PECE hydrogel composites based on previous work about collagen/n-HA/PECE
      hydrogel to exhibit better performance in guiding spinal fusion because of the
      addition of BMP-2@PCEC nanoparticles (PCEC, PCL-PEG-PCL). However, when the
      hydrogels were injected, one of the surfaces was in contact with the spine, but
      others were in contact with soft tissue like muscles and fascia. The release
      behavior was the same at the different surfaces, so the factors could be released
      into the soft tissue, and it may then be consumed or lead to ectopic bone
      formation. The hydrogel composites should be improved to adjust the direction of
      the releaser behavior. In consequence, we wrapped an electrostatic spinning
      nanofiber membrane possessing hydrophobicity around the hydrogels. In this study,
      we developed a system that the collagen/n-HA/BMP-2@PCEC/PECE hydrogels were
      wrapped with the hydrophobicity PDLLA electrospun nanofiber membrane, setting up
      a barrier between the hydrogels and the soft tissue. The system could exhibit
      biocompatibility, preventing the factors from escaping to keep their retention in
      the needed places of osteogenesis; the results demonstrated that it showed an
      excellent effect on spinal fusion.

PMID- 29338186
TI  - Editors' Favorites of 2017.

PMID- 29338188
TI  - Special Issue on Precision Medicine for Brain Cancer in ACS Chemical
      Neuroscience.

PMID- 29338189
TI  - Three-Phase Morphology Evolution in Sequentially Solution-Processed Polymer
      Photodetector: Toward Low Dark Current and High Photodetectivity.
AB  - Sequentially solution-processed polymer photodetectors (SSP PPDs) based on poly(3
      hexylthiophene-2,5-diyl) (P3HT)/[6,6]-phenyl C71-butyric acid methyl ester
      (PC71BM) are fabricated by depositing the top layers of PC71BM from an
      appropriate cosolvent of 2-chlorophenol (2-CP)/o-dichlorobenzene (ODCB) onto the
      predeposited bottom layers of P3HT. By adjusting the ratio of 2-CP/ODCB in the
      top PC71BM layers, the resulting SSP PPD shows a decreased dark current and an
      increased photocurrent, leading to a maximum detectivity of 1.23 * 1012 Jones at
      a wavelength of 550 nm. This value is 5.3-fold higher than that of the
      conventional bulk heterojunction PPD. Morphology studies reveal that the PC71BM
      partially penetrates the predeposited P3HT layer during the spin-coating process,
      resulting in an optimal three-phase morphology with one well-mixed interdiffusion
      P3HT/PC71BM phase in the middle of the bulk and two pure phases of P3HT and
      PC71BM at the two electrode sides. We show that the pure phases form high
      Schottky barriers (>2.0 eV) at the active layer/electrodes interface and
      efficiently block unfavorable reverse charge carrier injection by significantly
      decreasing the dark current. The interdiffussion phase enlarges the donor
      acceptor interfacial area leading to a large photocurrent. We also reveal that
      the improved performance of SSP PPDs is also due to the enhanced optical
      absorption, improved P3HT crystallinity, increased charge carrier mobilities, and
      suppressed bimolecular recombination.

PMID- 29338190
TI  - Cancer Cell Membrane-Biomimetic Nanoprobes with Two-Photon Excitation and Near
      Infrared Emission for Intravital Tumor Fluorescence Imaging.
AB  - Biomimetic fluorescent nanoprobes capable of emitting near-infrared (NIR)
      fluorescence (lambdamax ~ 720 nm) upon excitation of 800 nm light were developed.
      The key conjugated polymer enabled two-photon absorption and Forster resonance
      energy transfer (FRET) processes within the nanoprobes, which imparted the
      nanoprobes with ideal NIR-incoming-NIR-outgoing fluorescence features. The cancer
      cell membrane (CM) coating endowed these nanoprobes with perfect biocompatibility
      and highly specific targeting ability to homologous tumors. It was believed that
      CM encapsulation provided an additional protecting layer for the photoactive
      components residing in the core of nanoprobes for retaining their intrinsic
      fluorescing ability in the physiological milieu. The long-term structural
      integrity, excellent photostability (fluorescence decrease <10% upon 30 min
      illumination of 800 nm pulse laser), high NIR fluorescence quantum yield (~20%),
      and long in vivo circulation time of the target nanoprobes were also confirmed.
      The ability of these feature-packed nanoprobes for circumventing the challenges
      of absorption and light scattering caused by cellular structures and tissues was
      definitely confirmed via in vivo and in vitro experiments. The superior
      performances of these nanoprobes in terms of fluorescence signaling as well as
      targeting specificity were verified in intravital fluorescence imaging on tumor
      bearing model mice. Specifically, these nanoprobes unequivocally enabled high
      resolution visualization of the fine heterogeneous architectures of intravital
      tumor tissue, which proclaims the great potential of this type of probe for high
      contrast fluorescence detection of thick biological samples in practical
      applications.

PMID- 29338192
TI  - Under-Oil Switchable Superhydrophobicity to Superhydrophilicity Transition on
      TiO2 Nanotube Arrays.
AB  - Recently, smart interfacial materials that can reversibly transit between the
      superhydrophobicity and superhydrophilicity have aroused much attention. However,
      all present performances happen in air, and to realize such a smart transition in
      complex environments, such as oil, is still a challenge. Herein, TiO2 nanotube
      arrays with switchable transition between the superhydrophobicity and
      superhydrophilicity in oil are reported. The switching can be observed by
      alternation of UV irradiation and heating process, and the smart controllability
      can be ascribed to the cooperative effect between the surface nanostructures and
      the chemical composition variation. By using the controllable wetting
      performances, some applications such as under-oil droplet-based microreaction and
      water-removal from oil were demonstrated on our surface. This paper reports a
      surface with smart water wettability in oil, which could start some fresh ideas
      for wetting control on interfacial materials.

PMID- 29338191
TI  - Conjugate Polyplexes with Anti-Invasive Properties and Improved siRNA Delivery In
      Vivo.
AB  - This study reports on a simple method to prepare siRNA-polycation conjugate
      polyplexes by in situ thiol-disulfide exchange reaction. The conjugate polyplexes
      are prepared using thiol-terminated siRNA and a bioreducible branched
      polycationic inhibitor of the CXCR4 chemokine receptor (rPAMD). The rPAMD-SS
      siRNA conjugate polyplexes exhibit improved colloidal stability and resistance
      against disassembly with heparin, serum, and physiological salt concentrations
      when compared with control conventional rPAMD/siRNA polyplexes. Coating the
      polyplexes with human serum albumin masks the positive surface charge and
      contributes to the enhanced in vitro gene silencing and improved safety in vivo.
      The conjugate polyplexes display improved in vivo reporter gene silencing
      following intravenous injection in tumor-bearing mice. Because the conjugate
      polyplexes retained the ability of rPAMD to inhibit CXCR4 and restrict cancer
      cell invasion, the developed systems show promise for future combination anti
      metastatic siRNA therapies of cancer.

PMID- 29338193
TI  - Induction of Chirality in Two-Dimensional Nanomaterials: Chiral 2D MoS2
      Nanostructures.
AB  - Two-dimensional (2D) nanomaterials have been intensively investigated due to
      their interesting properties and range of potential applications. Although most
      research has focused on graphene, atomic layered transition metal dichalcogenides
      (TMDs) and particularly MoS2 have gathered much deserved attention recently.
      Here, we report the induction of chirality into 2D chiral nanomaterials by
      carrying out liquid exfoliation of MoS2 in the presence of chiral ligands
      (cysteine and penicillamine) in water. This processing resulted in exfoliated
      chiral 2D MoS2 nanosheets showing strong circular dichroism signals, which were
      far past the onset of the original chiral ligand signals. Using theoretical
      modeling, we demonstrated that the chiral nature of MoS2 nanosheets is related to
      the presence of chiral ligands causing preferential folding of the MoS2 sheets.
      There was an excellent match between the theoretically calculated and
      experimental spectra. We believe that, due to their high aspect ratio planar
      morphology, chiral 2D nanomaterials could offer great opportunities for the
      development of chiroptical sensors, materials, and devices for valleytronics and
      other potential applications. In addition, chirality plays a key role in many
      chemical and biological systems, with chiral molecules and materials critical for
      the further development of biopharmaceuticals and fine chemicals, and this
      research therefore should have a strong impact on relevant areas of science and
      technology such as nanobiotechnology, nanomedicine, and nanotoxicology.

PMID- 29338194
TI  - Sequential and Selective Detection of Two Molecules with a Single Solid-Contact
      Chronopotentiometric Ion-Selective Electrode.
AB  - A polymeric membrane ion-selective electrode (ISE) is typically designed for the
      determination of one specific ion using a conventional method. In this work, we
      demonstrate a simple, versatile, and sensitive platform for simultaneous
      detection of two molecules with a single ISE. Under a series of periodic
      galvanostatic polarization, a solid-contact ISE without ion exchanger properties
      under zero-current conditions has been successfully used for simultaneous
      detection of two opposite charged ions with high sensitivity, good selectivity,
      and fast reversibility. By integration of biorecognition elements with the
      potentiometric measurement, highly sensitive and selective detection of a broad
      range of different molecular targets can be predicted. As a proof of concept, a
      potentiometric genosensor based on magnetic beads-enzyme sandwich assay has been
      designed for sensitive and selective detection of pathogenic bacteria Escherichia
      coli O157:H7 and Staphylococcus aureus. Under optimal conditions, two bacteria
      nucleic acid sequences can be detected simultaneously with high sensitivity and
      good selectivity by using a single solid-contact potentiometric ISE. The
      detection limits of Escherichia coli O157:H7 DNA and Staphylococcus aureus DNA
      are 120 and 54 fM (3sigma), respectively. Because of its simplicity, this
      potentiometric technique based on ISE can be an attractive tool or detector to
      perform two analyte measurements.

PMID- 29338195
TI  - Mesoporous Silica Thin Films for Improved Electrochemical Detection of Paraquat.
AB  - An electrochemical method was developed for rapid and sensitive detection of the
      herbicide paraquat in aqueous samples using mesoporous silica thin film modified
      glassy carbon electrodes (GCE). Vertically aligned mesoporous silica thin films
      were deposited onto GCE by electrochemically assisted self-assembly (EASA).
      Cyclic voltammetry revealed effective response to the cationic analyte (while
      rejecting anions) thanks to the charge selectivity exhibited by the negatively
      charged mesoporous channels. Square wave voltametry (SWV) was then used to detect
      paraquat via its one electron reduction process. Influence of various
      experimental parameters (i.e., pH, electrolyte concentration, and nature of
      electrolyte anions) on sensitivity was investigated and discussed with respect to
      the mesopore characteristics and accumulation efficiency, pointing out the key
      role of charge distribution in such confined spaces on these processes.
      Calibration plots for paraquat concentration ranging from 10 nM to 10 MUM were
      constructed at mesoporous silica modified GCE which were linear with increasing
      paraquat concentration, showing dramatically enhanced sensitivity (almost 30
      times) as compared to nonmodified electrodes. Finally, real samples from Meuse
      River (France) spiked with paraquat, without any pretreatment (except
      filtration), were analyzed by SWV, revealing the possible detection of paraquat
      at very low concentration (10-50 nM). Limit of detection (LOD) calculated from
      real sample analysis was found to be 12 nM, which is well below the permissible
      limits of paraquat in drinking water (40-400 nM) in various countries.

PMID- 29338196
TI  - Method for High Frequency Underway N2 Fixation Measurements: Flow-Through
      Incubation Acetylene Reduction Assays by Cavity Ring Down Laser Absorption
      Spectroscopy (FARACAS).
AB  - Because of the difficulty in resolving the large variability of N2 fixation with
      current methods which rely on discrete sampling, the development of new methods
      for high-resolution measurements is highly desirable. We present a new method for
      high-frequency measurements of aquatic N2 fixation by continuous flow-through
      incubations and spectral monitoring of the acetylene (C2H2, a substrate analog
      for N2) reduction to ethylene (C2H4). In this method, named Flow-through
      Incubation Acetylene Reduction Assays by Cavity Ring-Down Laser Absorption
      Spectroscopy (FARACAS), dissolved C2H2 is continuously admixed with seawater
      upstream of a continuous-flow stirred-tank reactor (CFSR) in which C2H2 reduction
      takes place. Downstream of the flow-through incubator, the C2H4 gas is stripped
      using a bubble column contactor and circulated with a diaphragm pump into a
      wavelength-scanned cavity ring down laser absorption spectrometer (CRDS). Our
      method provides high-resolution and precise mapping of aquatic N2 fixation, its
      diel cycle, and its response to environmental gradients, and can be adapted to
      measure other biological processes. The short-duration of the flow-through
      incubations without preconcentration of cells minimizes potential artifacts such
      as bottle containment effects while providing near real-time estimates for
      adaptive sampling. We expect that our new method will improve the
      characterization of the biogeography and kinetics of aquatic N2 fixation rates.

PMID- 29338197
TI  - Modification of Vapor Phase Concentrations in MoS2 Growth Using a NiO Foam
      Barrier.
AB  - Single-layer molybdenum disulfide (MoS2) has attracted significant attention due
      to its electronic and physical properties, with much effort invested toward
      obtaining large-area high-quality monolayer MoS2 films. In this work, we
      demonstrate a reactive-barrier-based approach to achieve growth of highly
      homogeneous single-layer MoS2 on sapphire by the use of a nickel oxide foam
      barrier during chemical vapor deposition. Due to the reactivity of the NiO
      barrier with MoO3, the concentration of precursors reaching the substrate and
      thus nucleation density is effectively reduced, allowing grain sizes of up to 170
      MUm and continuous monolayers on the centimeter length scale being obtained. The
      quality of the monolayer is further revealed by angle-resolved photoemission
      spectroscopy measurement by observation of a very well resolved electronic band
      structure and spin-orbit splitting of the bands at room temperature with only two
      major domain orientations, indicating the successful growth of a highly
      crystalline and well-oriented MoS2 monolayer.

PMID- 29338198
TI  - Atomic Resolution Imaging of Nanoscale Chemical Expansion in PrxCe1-xO2-delta
      during In Situ Heating.
AB  - Thin film nonstoichiometric oxides enable many high-temperature applications
      including solid oxide fuel cells, actuators, and catalysis. Large concentrations
      of point defects (particularly, oxygen vacancies) enable fast ionic conductivity
      or gas exchange kinetics in these materials but also manifest as coupling between
      lattice volume and chemical composition. This chemical expansion may be either
      detrimental or useful, especially in thin film devices that may exhibit enhanced
      performance through strain engineering or decreased operating temperatures.
      However, thin film nonstoichiometric oxides can differ from bulk counterparts in
      terms of operando defect concentrations, transport properties, and mechanical
      properties. Here, we present an in situ investigation of atomic-scale chemical
      expansion in PrxCe1-xO2-delta (PCO), a mixed ionic-electronic conducting oxide
      relevant to electrochemical energy conversion and high-temperature actuation.
      Through a combination of electron energy loss spectroscopy and transmission
      electron microscopy with in situ heating, we characterized chemical strains and
      changes in oxidation state in cross sections of PCO films grown on yttria
      stabilized zirconia (YSZ) at temperatures reaching 650  degrees C. We quantified,
      both statically and dynamically, the nanoscale chemical expansion induced by
      changes in PCO redox state as a function of position and direction relative to
      the film-substrate interface. Additionally, we observed dislocations at the film
      substrate interface, as well as reduced cation localization to threading defects
      within PCO films. These results illustrate several key aspects of atomic-scale
      structure and mechanical deformation in nonstoichiometric oxide films that
      clarify distinctions between films and bulk counterparts and that hold several
      implications for operando chemical expansion or "breathing" of such oxide films.

PMID- 29338199
TI  - Enediyne-Comprising Amino Aldehydes in the Passerini Reaction.
AB  - Multicomponent reactions represent a highly efficient approach to a broad
      spectrum of structurally diverse compounds starting from simple and affordable
      compounds. A focused library of tweezers-like compounds is prepared by employing
      the multicomponent Passerini reaction comprising enediyne-derived amino
      aldehydes. The reaction proceeds under mild conditions yielding Passerini
      products in good to excellent yields. Postcondensation modifications of Passerini
      products are demonstrated through a simple deprotection/coupling approach
      comprising amino functionality, furnishing enediyne cores with highly decorated
      arms.

PMID- 29338200
TI  - Solid-Phase Synthesis of Oligopeptides Containing Sterically Hindered Amino Acids
      on Nonswellable Resin Using 3-Nitro-1,2,4-triazol-1-yl-tris(pyrrolidin-1
      yl)phosphonium Hexafluorophosphate (PyNTP) as the Condensing Reagent.
AB  - Peptides are still difficult to synthesize when they contain sterically hindered
      amino acids, such as alpha,alpha-disubstituted amino acids and N-substituted
      amino acids. In this study, solid-phase syntheses of oligopeptides containing
      multiple alpha-aminoisobutyric acid (Aib) residues were performed in high yields
      by using a nonswellable resin as the solid-support and 3-nitro-1,2,4-triazol-1-yl
      tris(pyrrolidin-1-yl)phosphonium hexafluorophosphate (PyNTP) as the condensing
      reagent.

PMID- 29338201
TI  - Self-Assembly of Spider Silk-Fusion Proteins Comprising Enzymatic and
      Fluorescence Activity.
AB  - The recombinant spider silk protein eADF4(C16) was genetically fused either with
      esterase 2 (EST2) or green fluorescent protein (GFP). The fusions EST-eADF4(C16)
      and GFP-eADF4(C16) were spectroscopically investigated and showed native
      structures of EST and GFP. The structural integrity was confirmed by the
      enzymatic activity of EST and the fluorescence of GFP. The spider silk moiety
      retained its intrinsically unstructured conformation in solution and the self
      assembly into either nanofibrils or nanoparticles could be controlled by the
      concentration of phosphate. Particles, however, showed significantly lower
      activity of the EST and GFP domains likely caused by a steric hindrance. However,
      upon self-assembly of EST-eADF4(C16) and GFP-eADF4(C16) into fibrils the protein
      activities were retained. In general, the fusion of globular enzymes with the
      spider silk domain allows the generation of fibrous biomaterials with catalytic
      or light emitting properties.

PMID- 29338202
TI  - Nanoscale Domain Imaging of All-Polymer Organic Solar Cells by Photo-Induced
      Force Microscopy.
AB  - Rapid nanoscale imaging of the bulk heterojunction layer in organic solar cells
      is essential to the continued development of high-performance devices.
      Unfortunately, commonly used imaging techniques such as tunneling electron
      microscopy (TEM) and atomic force microscopy (AFM) suffer from significant
      drawbacks. For instance, assuming domain identity from phase contrast or
      topographical features can lead to inaccurate morphological conclusions. Here we
      demonstrate a technique known as photo-induced force microscopy (PiFM) for
      imaging organic solar cell bulk heterojunctions with nanoscale chemical
      specificity. PiFM is a relatively recent scanning probe microscopy technique that
      combines an AFM tip with a tunable infrared laser to induce a dipole for chemical
      imaging. Coupling the nanometer resolution of AFM with the chemical specificity
      of a tuned IR laser, we are able to spatially map the donor and acceptor domains
      in a model all-polymer bulk heterojunction with resolution approaching 10 nm.
      Domain size from PiFM images is compared to bulk-averaged results from resonant
      soft X-ray scattering, indicating excellent quantitative agreement. Further, we
      demonstrate that in our all-polymer system, the AFM topography, AFM phase, and
      PiFM show poor correlation, highlighting the need to move beyond standard AFM for
      morphology characterization of bulk heterojunctions.

PMID- 29338203
TI  - Boron Analogue of Vinylidene Dication Supported by Phosphines.
AB  - In the presence of a catalytic amount of heavier tetrylene dichlorides, an
      allenic diborene 1 undergoes a 1,3-hydrogen shift to afford a terminal diborene
      2, which can be deemed a boron analogue of vinylidene dication stabilized by
      Lewis bases. X-ray diffraction analysis and computational studies revealed that 2
      involves a conjugative interaction between the C?C and B?B pi-orbitals. The
      reaction of 2 with ZnBr2 afforded the corresponding isolable complex 3, in which
      two boon centers coordinate to the Zn atom asymmetrically.

PMID- 29338204
TI  - Correction to Hydrogen Sulfide Capture: From Absorption in Polar Liquids to
      Oxide, Zeolite, and Metal-Organic Framework Adsorbents and Membranes.

PMID- 29338205
TI  - Control of Amphiphile Self-Assembly via Bioinspired Metal Ion Coordination.
AB  - Inspired by marine siderophores that exhibit a morphological shift upon metal
      coordination, hybrid peptide-polymer conjugates that assemble into different
      morphologies based on the nature of the metal ion coordination have been
      designed. Coupling of a peptide chelator, hexahistidine, with hydrophobic
      oligostyrene allows a modular strategy to be established for the efficient
      synthesis and purification of these tunable amphiphiles (oSt(His)6). Remarkably,
      in the presence of different divalent transition metal ions (Mn, Co, Ni, Cu, Zn,
      and Cd) a variety of morphologies were observed. Zinc(II), cobalt(II), and
      copper(II) led to aggregated micelles. Nickel(II) and cadmium(II) produced
      micelles, and multilamellar vesicles were obtained in the presence of
      manganese(II). This work highlights the significant potential for transition
      metal ion coordination as a tool for directing the assembly of synthetic
      nanomaterials.

PMID- 29338206
TI  - Application of Proton-Transfer-Reaction Mass Spectrometry (PTR-MS) and 33S
      Isotope Labeling for Monitoring Sulfur Processes in Livestock Waste.
AB  - Reduced sulfur compounds emitted from livestock production cause odor nuisance
      for local residents. The microbial processes responsible for this are not well
      described in swine manure and a method for monitoring the biological processes is
      necessary to develop strategic abatement technologies. In this study, Proton
      Transfer-Reaction Mass Spectrometry and isotope-labeled sulfate were combined and
      applied to elucidate the sulfur processes in swine manure with high time
      resolution. We successfully monitored reduction of isotope 33S labeled sulfate
      into corresponding 33S hydrogen sulfide and found that some of the 33S hydrogen
      sulfide was further methylated into 33S methanethiol. The isotope patterns in
      reduced sulfur compounds together with usage of inhibitors enabled us to
      calculate a sulfate reduction rate of 1.03 +/- 0.18 mM/day equivalent to 76.9 +/-
      3.0% of total hydrogen sulfide emissions. Cysteine degradation constituted 20.2
      +/- 2.7% of the total hydrogen sulfide produced and the remaining hydrogen
      sulfide came from demethylation of methanethiol and dimethyl sulfide. Another
      source to methanethiol, besides hydrogen sulfide methylation, was methionine
      degradation, which contributed with 78.3 +/- 2.5% of the methanethiol production,
      whereas the remaining 21.7 +/- 2.5% came from hydrogen sulfide methylation. This
      study suggests, therefore, that emissions of odorous sulfur compounds from swine
      manure can be reduced by inhibiting methionine degradation and sulfate reduction.

PMID- 29338207
TI  - Total Synthesis of (-)-Xylogranatopyridine B via a Palladium-Catalyzed Oxidative
      Stannylation of Enones.
AB  - We report a total synthesis of the pyridine-containing limonoid alkaloid (-)
      xylogranatopyridine B in 11 steps from commercially available dihydrocarvone. The
      central pyridine ring was assembled by a late-stage fragment coupling approach
      employing a modified Liebeskind pyridine synthesis. One fragment was prepared by
      an allyl-palladium catalyzed oxidative enone beta-stannylation, in which the key
      bimetallic beta-stannyl palladium enolate intermediate undergoes a beta-hydride
      elimination. This methodology also allowed introduction of alkyl and silyl groups
      to the beta-position of enones.

PMID- 29338208
TI  - Hierarchical Composite Membranes with Robust Omniphobic Surface Using Layer-By
      Layer Assembly Technique.
AB  - In this study, composite membranes were fabricated via layer-by-layer (LBL)
      assembly of negatively charged silica aerogel (SiA) and 1H,1H,2H,2H
      perfluorodecyltriethoxysilane (FTCS) on a polyvinylidene fluoride phase inversion
      membrane and interconnecting them with positively charged
      poly(diallyldimethylammonium chloride) (PDDA) via electrostatic interaction. The
      results showed that the PDDA-SiA-FTCS coated membrane had significantly enhanced
      the membrane structure and properties. New trifluoromethyl and
      tetrafluoroethylene bonds appeared at the surface of the coated membrane, which
      led to lower surface free energy of the composite membrane. Additionally, the LBL
      membrane showed increased surface roughness. The improved structure and property
      gave the LBL membrane an omniphobic property, as indicated by its good wetting
      resistance. The membrane performed a stable air gap membrane distillation (AGMD)
      flux of 11.22 L/m2 h with very high salt rejection using reverse osmosis brine
      from coal seam gas produced water as feed with the addition of up to 0.5 mM SDS
      solution. This performance was much better compared to those of the neat
      membrane. The present study suggests that the enhanced membrane properties with
      good omniphobicity via LBL assembly make the porous membranes suitable for long
      term AGMD operation with stable permeation flux when treating challenging saline
      wastewater containing low surface tension organic contaminants.

PMID- 29338209
TI  - Injectable Self-Healing Zwitterionic Hydrogels Based on Dynamic Benzoxaborole
      Sugar Interactions with Tunable Mechanical Properties.
AB  - Dynamic hydrogels based on arylboronic esters have been considered as ideal
      platforms for biomedical applications given their self-healing and injectable
      characteristics. However, there still exist some critical issues that need to be
      addressed or improved, including hydrogel biocompatibility, physiological
      usability, and tunability of mechanical properties. Here, two kinds of
      phospholipid bioinspired MPC copolymers, one is zwitterionic copolymer (PMB)
      containing a fixed 15 mol % of benzoxaborole (pKa ~ 7.2) groups and the other is
      zwitterionic glycopolymers (PMG) with varied ratios of sugar groups (20%, 50%,
      80%), were synthesized respectively via one-pot facile reversible addition
      fragmentation chain transfer (RAFT) polymerization. PMBG hydrogels were formed
      spontaneously after mixing 10 wt % of PMB and PMG copolymer solutions because of
      dynamic benzoxaborole-sugar interactions. The mechanical properties of nine
      hydrogels (3 * 3) with different sugar contents and pHs (7.4, 8.4, 9.4) were
      carefully studied by rheological measurements, and hydrogels with higher sugar
      content and higher pH were found to have higher strength. Moreover, similar to
      other arylboronic ester-based hydrogels, PMBG hydrogels possessed not only self
      healing and injectable properties but also pH/sugar responsiveness. Additionally,
      in vitro cytotoxicity tests of gel extracts on both normal and cancer cells
      further confirmed the excellent biocompatibility of the hydrogels, which should
      be ascribed to the biomimetic nature of phosphorylcholine (PC) and sugar residues
      of the copolymers. Consequently, the zwitterionic dynamic hydrogels provide
      promising future for diverse biomedical applications.

PMID- 29338210
TI  - An Emission-Free Vacuum Chlorinating Process for Simultaneous Sulfur Fixation and
      Lead Recovery from Spent Lead-Acid Batteries.
AB  - Spent lead-acid battery recycling by using conventional technologies is usually
      accompanied by releases of lead-containing wastewater as well as emissions of
      sulfur oxides and lead particulates that may potentially cause secondary
      pollution. This study developed a vacuum chlorinating process for simultaneous
      sulfur fixation and high-purity lead chloride (PbCl2) recovery from spent lead
      paste by using calcium chloride (CaCl2) and silicon dioxide (SiO2) as reagents.
      The process train includes pretreatment, simultaneous PbCl2 production and sulfur
      fixation, and PbCl2 volatilization. The pretreatment eliminated chlorine emission
      from direct chlorinating reaction of PbO2 in the initial S-paste
      (PbSO4/PbO2/PbO/Pb). During the subsequent PbCl2 production and sulfur fixation
      step, lead compounds in the P-paste (PbSO4/PbO) was converted to volatile PbCl2,
      and sulfur was simultaneously fixed to the solid residues in the form of CaSO4 to
      eliminate the emission of sulfur oxides. The final step, PbCl2 volatilization
      under vacuum, is a physical phase-transformation process of ionic crystals,
      following a zeroth-order kinetic model. A cost estimate indicates a profit of USD
      $ 8.50/kg PbCl2. This process offers a novel green lead recovery alternative for
      spent lead-acid batteries with environmental and economic benefits.

PMID- 29338211
TI  - Highly Stable RNA Capture by Dense Cationic Polymer Brushes for the Design of
      Cytocompatible, Serum-Stable SiRNA Delivery Vectors.
AB  - The high density of polymer brushes confers to these coatings unique
      physicochemical properties, in particular for the regulation of biomolecular
      interaction and the design of highly selective coatings for biosensors and
      protein patterning. Here, we show that high density poly(dimethylaminoethyl
      methacrylate) cationic polymer brushes enable the stable uptake of high levels of
      oligonucleotides. This is proposed to result from the high degree of crowding and
      associated increase in entropic driving force for the binding of polyelectrolytes
      such as nucleic acid molecules. We further demonstrate the ease with which such
      coatings allow the design of highly structured nanomaterials for siRNA delivery
      using block copolymer-brush-based nanoparticles that allow the protection of
      oligonucleotides by a protein-resistant outer block. In particular, these
      nanomaterials display a high serum stability and low cytotoxicity while retaining
      excellent knock down efficiencies. Polymer brush-based nanomaterials therefore
      appear particularly attractive for the rational design of a new generation of
      high performance theranostics and RNA delivery probes.

PMID- 29338212
TI  - Catalytic Dehydrogenative Stannylation of C(sp)-H Bonds Involving Cooperative Sn
      H Bond Activation of Hydrostannanes.
AB  - The catalytic generation of a stannylium-ion-like tin electrophile by heterolytic
      cleavage of the Sn-H bond in hydrostannanes at the Ru-S bond of Ohki-Tatsumi
      complexes is reported. Reacting these activated hydrostannanes with terminal
      acetylenes does not lead to hydrostannylation of the C-C triple bond but to
      dehydrogenative stannylation of the alkyne terminus. The scope of this rare
      direct C(sp)-H bond stannylation with hydrostannanes is broad, and a mechanism
      involving a beta-tin-stabilized vinyl cation likely having a bridged structure is
      presented.

PMID- 29338213
TI  - Selective Dehydrogenative Coupling of Ethylene to Butadiene via an
      Iridacyclopentane Complex.
AB  - An iridium complex is found to catalyze the selective dehydrogenative coupling of
      ethylene to 1,3-butadiene. The key intermediate, and a major resting state, is an
      iridacyclopentane that undergoes a surprisingly facile beta-H elimination,
      enabled by a partial dechelation (kappa3-kappa2) of the supporting 3,5
      dimethylphenyl-2,6-bis(oxazolinyl) ligand.

PMID- 29338215
TI  - Improving Flue Gas Mercury Removal in Waste Incinerators by Optimization of
      Carbon Injection Rate.
AB  - This study tested the mercury emission characteristics of six municipal solid
      waste incinerators (MSWIs) and recommended future mercury control via adjusting
      operational parameters. The results indicated that over 99% of the mercury in
      solid wastes ended in fly ash and flue gas, of which 3.3-66.3% was emitted to air
      through stack gas. Mercury in the stack gas was mainly in the form of oxidized
      mercury (Hg2+), the proportion (65.4-89.0%) of which was far higher than previous
      estimation (15%). Mercury removal efficiencies (MRE) of the tested incinerators
      were in the range of 33.6-95.2%. The impact of waste incineration capacity, gas
      flow, fly ash yield, and activated carbon (AC) injection on MRE were analyzed. We
      found that the MRE was significantly linearly correlated to the ratio of AC
      injection and fly ash yield (correlation coefficient = 0.98, significance <0.01).
      AC injection value is determined based on the control of dioxin emissions without
      considering mercury control in traditional design. To increase MRE of MSWIs, the
      AC injection should increase from around 100 mg.Nm-3 to 135 mg.Nm-3 for grate
      furnace combustor and 170 mg.Nm-3 for circulation fluidized bed combustor, so as
      to reach a MRE of 90%.

PMID- 29338214
TI  - A Tool for the Import of Natural and Unnatural Nucleoside Triphosphates into
      Bacteria.
AB  - Nucleoside triphosphates play a central role in biology, but efforts to study
      these roles have proven difficult because the levels of triphosphates are tightly
      regulated in a cell and because individual triphosphates can be difficult to
      label or modify. In addition, many synthetic biology efforts are focused on the
      development of unnatural nucleoside triphosphates that perform specific functions
      in the cellular environment. In general, both of these efforts would be
      facilitated by a general means to directly introduce desired triphosphates into
      cells. Previously, we demonstrated that recombinant expression of a nucleoside
      triphosphate transporter from Phaeodactylum tricornutum (PtNTT2) in Escherichia
      coli functions to import triphosphates that are added to the media. Here, to
      explore the generality and utility of this approach, we report a structure
      activity relationship study of PtNTT2. Using a conventional competitive uptake
      inhibition assay, we characterize the effects of nucleobase, sugar, and
      triphosphate modification, and then develop an LC-MS/MS assay to directly measure
      the effects of the modifications on import. Lastly, we use the transporter to
      import radiolabeled or 2'-fluoro-modified triphosphates and quantify their
      incorporation into DNA and RNA. The results demonstrate the general utility of
      the PtNTT2-mediated import of natural or modified nucleoside triphosphates for
      different molecular or synthetic biology applications.

PMID- 29338216
TI  - Effect of Thermochemical Synthetic Conditions on the Structure and Dielectric
      Properties of Ga1.9Fe0.1O3 Compounds.
AB  - We report on the tunable and controlled dielectric properties of iron (Fe)-doped
      gallium oxide (Ga2O3; Ga1.9Fe0.1O3, referred to as GFO) inorganic compounds. The
      GFO materials were synthesized using a standard high-temperature, solid-state
      chemical reaction method by varying the thermochemical processing conditions,
      namely, different calcination and sintering environments. Structural
      characterization by X-ray diffraction revealed that GFO compounds crystallize in
      the beta-Ga2O3 phase. The Fe doping has induced slight lattice strain in GFO,
      which is evident in structural analysis. The effect of the sintering temperature
      (Tsint), which was varied in the range of 900-1200  degrees C, is significant, as
      revealed by electron microscopy analysis. Tsint influences the grain size and
      microstructure evolution, which, in turn, influences the dielectric and
      electrical properties of GFO compounds. The energy-dispersive X-ray spectrometry
      and mapping data demonstrate the uniform distribution of the elemental
      composition over the microstructure. The temperature- and frequency-dependent
      dielectric measurements indicate the characteristic features that are
      specifically due to Fe doping in Ga2O3. The spreading factor and relaxation time,
      calculated using Cole-Cole plots, are in the ranges of 0.65-0.76 and 10-4 s,
      respectively. The results demonstrate that densification and control over the
      microstructure and properties of GFO can be achieved by optimizing Tsint.

PMID- 29338217
TI  - Unprecedented Synergistic Effects of Nanoscale Nutrients on Growth, Productivity
      of Sweet Sorghum [Sorghum bicolor (L.) Moench], and Nutrient Biofortification.
AB  - Evidence-based synergistic effects of nanoscale materials (size of <100 nm in at
      least one dimension) were scantly documented in agriculture at field scale.
      Herein, we report for the first time on effects of nanoscale zinc oxide (n-ZnO),
      calcium oxide (n-CaO), and magnesium oxide (n-MgO) on growth and productivity of
      sweet sorghum [Sorghum bicolor (L.) Moench]. A modified sol-gel method was used
      to prepare nanoscale materials under study. Characterization was performed using
      transmission and scanning electron microscopies, X-ray diffraction, and dynamic
      light scattering. Average sizes (25, 53.7, and 53.5 nm) and zeta potentials (
      10.9, -28.2, and -16.2 mV) of n-ZnO, n-CaO, and n-MgO were measured,
      respectively. The significant grain yield (17.8 and 14.2%), cane yield (7.2 and
      8.0%), juice yield (10 and 12%), and higher sucrose yield (21.8 and 20.9%) were
      recorded with the application of nanoscale materials in the years 2014 and 2015,
      respectively. Nutrient uptake was significant with foliar application of
      nanoscale nutrients.

PMID- 29338218
TI  - Mimicking the Key Functions of Photosystem II in Artificial Photosynthesis for
      Photoelectrocatalytic Water Splitting.
AB  - It has been anticipated that learning from nature photosynthesis is a rational
      and effective way to develop artificial photosynthesis system, but it is still a
      great challenge. Here, we assembled a photoelectrocatalytic system by mimicking
      the functions of photosystem II (PSII) with BiVO4 semiconductor as a light
      harvester protected by a layered double hydroxide (NiFeLDH) as a hole storage
      layer, a partially oxidized graphene (pGO) as biomimetic tyrosine for charge
      transfer, and molecular Co cubane as oxygen evolution complex. The integrated
      system exhibited an unprecedentedly low onset potential (0.17 V) and a high
      photocurrent (4.45 mA cm-2), with a 2.0% solar to hydrogen efficiency.
      Spectroscopic studies revealed that this photoelectrocatalytic system exhibited
      superiority in charge separation and transfer by benefiting from mimicking the
      key functions of PSII. The success of the biomimetic strategy opened up new ways
      for the rational design and assembly of artificial photosynthesis systems for
      efficient solar-to-fuel conversion.

PMID- 29338219
TI  - Pretargeted Immuno-PET Based on Bioorthogonal Chemistry for Imaging EGFR Positive
      Colorectal Cancer.
AB  - Pretargeted immuno-PET imaging based on the bioorthogonal chemistry between 18F
      labeled Reppe anhydride derivatives and tetrazine conjugates of the EGFR-specific
      monoclonal antibodies cetuximab and panitumumab was performed. This pretargeting
      approach yielded high target-to-nontarget ratios. Furthermore, due to the fast
      clearance rate of the PET probe, the overall radiation burden to nontarget
      tissues was also substantially decreased.

PMID- 29338220
TI  - The Multiple Role of Bromide Ion in PPCPs Degradation under UV/Chlorine
      Treatment.
AB  - This study investigated the role of bromide ions in the degradation of nine
      pharmaceuticals and personal care products (PPCPs) during the UV/chlorine
      treatment of simulated drinking water containing 2.5 mgC L-1 natural organic
      matter (NOM). The kinetics of contributions from UV irradiation and from
      oxidation by free chlorine, free bromine, hydroxyl radical and reactive halogen
      species were evaluated. The observed loss rate constants of PPCPs in the presence
      of 10 MUM bromide were 1.6-23 times of those observed in the absence of bromide
      (except for iopromide and ibuprofen). Bromide was shown to play multiple roles in
      PPCP degradation. It reacts rapidly with free chlorine to produce a trace amount
      of free bromine, which then contributes to up to 55% of the degradation of some
      PPCPs during 15 min of UV/chlorine treatment. Bromide was also shown to reduce
      the level of HO* and to change the reactive chlorine species to bromine
      containing species, which resulted in decreases in ibuprofen degradation and
      enhancement in carbamazepine and caffeine degradation, respectively. Reactive
      halogen species contributed to between 37 and 96% of the degradation of the
      studied PPCPs except ibuprofen in the presence of 10 MUM bromide ion. The effect
      of bromide is non-negligible during the UV/chlorine treatment.

PMID- 29338221
TI  - Synthetic Strategy toward the Pentacyclic Core of Melodinus Alkaloids.
AB  - The three-component Povarov reaction is efficiently utilized for construction of
      the pentacyclic framework of complex Melodinus alkaloids, which is amenable to
      expansion to other complex natural products. The key steps were Povarov reaction,
      one-pot reductive cyclization, and ring-closing metathesis (RCM) reaction.

PMID- 29338222
TI  - Computational Modeling of a Caged Methyl Cation: Structure, Energetics, and
      Vibrational Analysis.
AB  - DFT calculations for CH3+ within a constrained cage of water molecules permit the
      controlled manipulation of distances rax and req to "axial" and "equatorial"
      waters. Equatorial CH...O interactions catalyze methyl transfer (MT) between
      axial waters. Variation in rax has a greater effect on CH bond lengths and
      stretching force constants in the symmetric SN2-like transition structures than
      variation in req. In-plane bending frequencies are insensitive to these
      variations in cage dimensions, but axial interactions loosen the out-of-plane
      bending mode (OP) whereas equatorial interactions stiffen it. Frequencies for
      rotational and translational motions of CH3+ within the cage are influenced by
      rax and req. In particular, translation of CH3+ in the axial direction is always
      coupled to cage motion. With longer rax, CH3+ translation is coupled with
      asymmetric CO bond stretching, but with shorter rax, it is also coupled with OP
      (equivalent to the umbrella mode of trigonal bipyramidal O...CH3+...O); the
      magnitude of the imaginary MT frequency increases steeply as rax diminishes. This
      coupling between CH3+ and its cage is removed by eliminating the rows and columns
      associated with cage atoms from the full Hessian to obtain a reduced Hessian for
      CH3+ alone. Within a certain range of cage dimensions, the reduced Hessian yields
      a real frequency for MT. The importance of using a Hessian large enough to
      describe the reaction coordinate mode correctly is emphasized for modeling
      chemical reactions and particularly for kinetic isotope effects in enzymic MT.

PMID- 29338223
TI  - Chemo-enzymatic Synthesis of Clickable Xylo-oligosaccharide Monomers from
      Hardwood 4-O-Methylglucuronoxylan.
AB  - A chemo-enzymatic pathway was developed to transform 4-O-methylglucuronic acid
      (MeGlcpA) containing xylo-oligosaccharides from beechwood into clickable monomers
      capable of polymerizing at room temperature and in aqueous conditions to form
      unique polytriazoles. While the gluco-oligosaccharide oxidase (GOOX) from
      Sarocladium strictum was used to oxidize C6-propargylated oligosaccharides, the
      acid-amine coupling reagents 1-ethyl-3-(3-(dimethylamino)propyl) carbodiimide
      (EDAC) and 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride
      (DMT-MM) were employed and compared for their ability to append click
      functionalities to carboxylic acid groups of enzyme-treated oligosaccharides.
      While DMT-MM was a superior coupling reagent for this application, a triazine
      side product was observed during C-1 amidation. Resulting bifunctional xylo
      oligosaccharide monomers were polymerized using a Cu(I) catalyst, forming a soft
      gel which was characterized by 1H NMR, confirming the triazole product.

PMID- 29338224
TI  - Deviation from the trans-Effect in Ligand-Exchange Reactions of Zeise's Ions
      PtCl3(C2H4)- with Heavier Halides (Br-, I-).
AB  - Four new Zeise's family ions with mixed-halide ligands, i.e., PtClnX3-n(C2H4)- (X
      = Br, I; n = 1, 2), were synthesized via ligand-exchange reactions of KX salts
      with KPtCl3(C2H4) in aqueous solutions, and were detected in vacuum via
      electrospray ionization mass spectrometry. Their photoelectron spectra reveal a
      series of well-resolved spectral peaks with their electron binding energies
      (EBEs) decreasing with increasing halide size, with I having a much stronger
      effect than Br, i.e., 4.57 (-Cl3) > 4.56 (-Cl2Br) > 4.53 (-ClBr2) > 4.34 (-Cl2I)
      > 4.30 eV (-ClI2). Ab initio electronic structure calculations including spin
      orbit coupling (SOC) predict that the cis- and trans-isomers are nearly
      isoenergetic with the cis-isomer for -Cl2X and the trans-isomer for -ClX2
      slightly favored, respectively. Excited-state spectra calculated with time
      dependent density functional theory (TDDFT), and their comparison with the
      observed ones, suggest that for each species both the cis- and trans
      configurations coexist in the experiments and contribute to the observed spectra,
      a fact that clearly deviates from the prediction of the widely accepted trans
      effect, which suggests that only one isomer would have formed.

PMID- 29338225
TI  - Stereoselective Photodimerization of 3-Arylindenones in Solution and in the Solid
      State.
AB  - Photodimerization of 3-arylindenones in solution and in the solid state was
      examined. Irradiation of 3-arylindenones in benzene exclusively gave C2-symmetric
      anti-HH cyclobutane dimers in good yields. In contrast, photolysis in the solid
      state afforded syn-HH cyclobutane dimers efficiently, which was considerably
      influenced by the molecular arrangement in the crystal lattice.

PMID- 29338226
TI  - Prenylated 2-Phenoxychromones and Flavonoids from Epimedium brevicornum and
      Revised Structures of Epimedonins A and B.
AB  - Six hitherto unknown prenylated 2-phenoxychromones, epimedonin G (1), 7-O
      methylepimedonin G (2), and epimedonins H-K (3-6), and two new prenylflavonoids,
      epimedonin L (7) and 3"-O-desmethylspinorhamnoside (8), were isolated from an
      ethanol extract of the aerial parts of Epimedium brevicornum. Their structures
      were established on the basis of spectroscopic data interpretation. Compound 7
      exhibited cytotoxic activity when evaluated against four human cancer cell lines
      (HL-60, A-549, MCF-7, and SW-480), with IC50 values of <10 MUM. In addition, the
      structures of epimedonins A and B (9a, 10a), recently isolated from E. koreanum,
      were corrected by reanalysis of the published NMR data.

PMID- 29338227
TI  - Entangled Photonic-Nuclear Molecular Dynamics of LiF in Quantum Optical Cavities.
AB  - The quantum photodynamics of a simple diatomic molecule with a permanent dipole
      immersed within an optical cavity containing a quantized radiation field is
      studied in detail. The chosen molecule under study, lithium fluoride (LiF), is
      characterized by the presence of an avoided crossing between the two lowest
      1Sigma potential energy curves (covalent-ionic diabatic crossing). Without field,
      after prompt excitation from the ground state 1 1Sigma, the excited nuclear wave
      packet moves back and forth in the upper 2 1Sigma state, but in the proximity of
      the avoided crossing, the nonadiabatic coupling transfers part of the nuclear
      wave packet to the lower 1 1Sigma state, which eventually leads to dissociation.
      The quantized field of a cavity also induces an additional light crossing in the
      modified dressed potential energy curves with similar transfer properties. To
      understand the entangled photonic-nuclear dynamics, we solve the time-dependent
      Schrodinger equation by using the multiconfigurational time-dependent Hartree
      method (MCTDH). The single mode quantized field of the cavity is represented in
      the coordinate space instead of in the Fock space, which allows us to deal with
      the field as an additional vibrational mode within the MCTDH procedure on equal
      footing. We prepare the cavity with different quantum states of light, namely,
      Fock states, coherent states, and squeezed coherent states. Our results reveal
      pure quantum light effects on the molecular photodynamics and the dissociation
      yields of LiF, which are quite different from the light-undressed case and which
      cannot be described in general by a semiclassical approach using classical
      electromagnetic fields.

PMID- 29338228
TI  - Total Synthesis and Structural Determination of XR774, a Tyrosine Kinase
      Inhibitor.
AB  - Total synthesis and structural determination of XR774 has been accomplished. The
      benzo[ j]fluoranthene skeleton has been constructed by regioselective coupling
      between tetraline 3 and tetralone 4 successively followed by the sequential
      transformation including the Birch reduction to prepare allylic alcohol,
      simultaneous bromination of vinylic and aromatic moieties, and the nickel
      mediated intramolecular coupling reaction. The optical resolution of racemic 17
      led to the first total synthesis of (-)-XR774.

PMID- 29338229
TI  - Reconstitution of Kinamycin Biosynthesis within the Heterologous Host
      Streptomyces albus J1074.
AB  - Diazofluorene compounds such as kinamycin and lomaiviticin feature unique
      molecular structures and compelling medicinal bioactivities. However, a complete
      understanding of the biosynthetic details for this family of natural products has
      yet to be fully elucidated. In addition, a lack of genetically and technically
      amenable production hosts has limited access to the full medicinal potential of
      these compounds. Here, we report the capture of the complete kinamycin gene
      cluster from Streptomyces galtieri Sgt26 by bacterial artificial chromosome
      cloning, confirmed by successful production of kinamycin in the heterologous host
      Streptomyces albus J1074. Sequence analysis and a series of gene deletion
      experiments revealed the boundary of the cluster, which spans 75 kb DNA. To probe
      the last step in biosynthesis, acetylation of kinamcyin F to kinamycin D, gene
      knockout, and complementation experiments identified a single gene product
      involved with final acetylation conversions. This study provides full genetic
      information for the kinamycin gene cluster from S. galtieri Sgt26 and establishes
      heterologous biosynthesis as a production platform for continued mechanistic
      assessment of compound formation and utilization.

PMID- 29338230
TI  - Organosilicon Reducing Reagents for Stereoselective Formations of Silyl Enol
      Ethers from alpha-Halo Carbonyl Compounds.
AB  - Salt-free stereoselective synthesis of silyl enol ethers was achieved by treating
      alpha-halo carbonyl compounds with 2,3,5,6-tetramethyl-1,4-bis(trimethylsilyl)
      1,4-dihydropyrazine. In this reaction, easily removable trimethylsilyl halides
      and 2,3,5,6-tetramethylpyrazine were generated as the reaction byproducts. Due to
      the inertness of the reaction byproducts, we found a one-pot transformation of
      the in situ generated silyl enol ethers into various alpha-functionalized
      carbonyls by reaction with Togni-II reagent or aldehydes.

PMID- 29338231
TI  - Fluorous-Phase Approach to alpha-Hydroxytropolone Synthesis.
AB  - alpha-Hydroxytropolones (alphaHTs) are troponoids that demonstrate inhibition
      against an array of therapeutically significant targets, making them potential
      drug leads for several human diseases. We have utilized a recently discovered one
      pot three-component oxidopyrylium cycloaddition in a solid-supported synthesis of
      alphaHTs. Though the procedure is time efficient and generates assay-ready
      molecules, the system suffers from low yields and an inability to perform
      reaction modifications on resin-bound intermediates. In order to combat these
      issues with the solid-phase platform, we incorporated fluorous tags into our
      synthetic route. Through the implementation of fluorous phase chemistry, we
      demonstrate a substantial increase in the overall yield of alphaHTs, as well as
      an ability to execute metal-catalyzed cross coupling and amide coupling on
      fluorous tagged intermediates. We also show that tagged molecules can be
      separated from nonfluorous impurities, and vice versa, by utilizing fluorous
      liquid-liquid and solid-phase extractions. Hence, these proof-of-principle
      investigations describe the viability of a fluorous phase approach to alphaHT
      synthesis and its potential to serve as a combinatorial technique to produce
      structurally diverse substrates.

PMID- 29338232
TI  - Improved Descriptors for the Quantitative Structure-Activity Relationship
      Modeling of Peptides and Proteins.
AB  - The ability to model the activity of a protein using quantitative structure
      activity relationships (QSAR) requires descriptors for the 20 naturally coded
      amino acids. In this work we show that by modifying some established descriptors
      we were able to model the activity data of 140 mutants of the enzyme epoxide
      hydrolase with improved accuracy. These new descriptors (referred to as physical
      descriptors) also gave very good results when tested against a series of four
      dipeptide data sets. The physical descriptors encode the amino acids using only
      two orthogonal scales: the first is strongly linked to
      hydrophilicity/hydrophobicity, and the second, to the volume of the amino acid
      residue. The use of these new amino acid descriptors should result in simpler and
      more readily interpretable models for the enzyme activity (and potentially other
      functions of interest, e.g., secondary and tertiary structure) of peptides and
      proteins.

PMID- 29338233
TI  - Evaluation of the Giant Ferromagnetic pi-d Interaction in Iron-Phthalocyanine
      Molecule.
AB  - The interaction between itinerant pi and localized d electrons in metal
      phthalocyanines, namely, Jpid interaction, is considered as responsible for the
      giant negative magnetoresistance observed in several phthalocyanine-based
      conductors, among many other important physical properties. Despite the
      fundamental and technological importance of this on-site intramolecular
      interaction, its giant ferromagnetic nature has been only recently demonstrated
      by the experiments conducted by Murakawa et al. in the neutral radical
      [Fe(Pc)(CN)2].2CHCl3 ( Phys. Rev. B 2015 , 92 , 054429 ). In this article, we
      present the theoretical evaluation of this interaction combining wave function
      based electronic calculations on isolated Fe(Pc)(CN)2 molecules and density
      functional theory-based periodic calculations on the crystal. Our calculations
      confirm the ferromagnetic nature of the pi-d interaction, with a coupling
      constant as large as Jpid/kB = 570 K, in excellent agreement with the
      experiments, and the presence of intermolecular antiferromagnetic interactions
      driven by the pi-pi overlap of neighboring phthalocyaninato molecules. The
      analysis of the wave function of the ground state of the Fe(Pc)(CN)2 molecule
      provides the clues of the origin of this giant ferromagnetic pi-d interaction.

PMID- 29338234
TI  - Role of Reaction Conditions in the Global and Local Two Parabolas Charge Transfer
      Model.
AB  - The local and global charge transfer approach based on the two parabolas model is
      applied to several problems aiming to show the importance of incorporating the
      reaction conditions to evaluate the global and local chemical descriptors. It is
      shown that, by preparation of the reactants, the chemical potentials of the
      reacting species determined by the two parabolas model satisfy the condition for
      the transfer of electrons in the direction dictated by the chemical potential
      difference. The model is applied to the hydration of alkenes, showing that it
      recovers Markovnikov's rule, to aromatic nitration, and to the interaction of
      nitrobenzenes with 1,3-diethylurea, an electrochemically controlled hydrogen
      bonding problem. The applications presented show that to satisfy the charge
      transfer directionality established by the chemical potential differences
      obtained from the two parabolas model, one has to incorporate the reaction
      conditions in the evaluation of the global and local chemical descriptors. The
      global and local charge transfer predicted along these lines allows one to
      determine the direction of electron transfer prevailing in the reaction and also
      the most relevant atoms participating in the interactions between the reactants,
      aiding in the unraveling of the chemical interactions present in the system under
      investigation.

PMID- 29338235
TI  - Enantioselective Dearomatization of Alkylpyridiniums by N-Heterocyclic Carbene
      Catalyzed Nucleophilic Acylation.
AB  - A chiral NHC-catalyzed dearomatizing reaction of activated N-alkylpyridinium
      salts with aliphatic aldehydes is described. The resulting acylated 1,4
      dihydropyridines have been obtained with complete C4 regioselectivity and
      enantioselectivities in the range 52-78% ee. The (4R)-absolute configuration of
      the synthesized compounds has been determined by the TD-DFT simulation of the
      electronic circular dichroism spectra.

PMID- 29338236
TI  - Detection of the Cytotoxic Penitrems A-F in Cheese from the European Single
      Market by HPLC-MS/MS.
AB  - Penitrems are fungal indole diterpene-derived tremorgenic secondary metabolites,
      which are mainly produced by Penicillium spp. Several cases of intoxications with
      penitrems and subsequent occurrences of penitrem A in foodstuff underline the
      need for reliable quantitation methods for the detection of these mycotoxins in
      food. In this study, a simple and fast high-performance liquid chromatography
      tandem mass spectrometry (HPLC-MS/MS) method for the quantitative analysis of
      penitrems A-F in cheese was developed. Therefore, penitrems A-F were isolated
      from Penicillium crustosum as analytical reference standards. The analysis of 60
      cheese samples from the European single market (EU) revealed the occurrence of
      penitrem A in 10% of the analyzed samples with an average concentration of 28.4
      MUg/kg and a maximum concentration of 429 MUg/kg. In addition to penitrem A,
      other members of the group of penitrems, namely, penitrems B, C, D, E, and F,
      were for the first time quantitatively detected in food samples, although in
      lower concentrations and with lower incidence in comparison to penitrem A.
      Moreover, we report cytotoxic effects of all penitrems on two cell lines (HepG2
      and CCF-STTG1). This clearly underlines their relevance and the importance to
      analyze food samples in order to get insights into the human exposure toward
      these mycotoxins.

PMID- 29338237
TI  - Reactivity of Metal Carbenes with Olefins: Theoretical Insights on the Carbene
      Electronic Structure and Cyclopropanation Reaction Mechanism.
AB  - Present work addresses the reactivity of several phenyl-substituted metal-carbene
      complexes with 4-methylstyrene by means of density functional theory OPBE
      simulations. Different paths that lead to cyclopropanation were explored and
      compared to the olefin metathesis mechanism. For this purpose, we chose four
      different catalysts: (i) the Grubbs second-generation olefin metathesis catalyst,
      (ii) a Grubs second-generation-like complex, in which ruthenium is replaced by
      iron, and (iii) two iron carbene complexes (a piano stool and a porphyrin iron
      carbene) that experimentally catalyze alkene cyclopropanation. Results suggest
      that the nature of the applying mechanism is very sensitive to the coordination
      around the metal center and the spin state of the metal-carbene complex.
      Cyclopropanation by open-shell metal-carbene complexes seems to preferentially
      proceed through a two-step radical mechanism, in which the two C-C bonds are
      sequentially formed (path C). Singlet-state carbenes proceed either through a
      direct attack of the olefin to the carbene (path D) when the formation of the
      metallacycle is not feasible or through a reductive elimination from the
      metallacyclobutane when this intermediate is accessible both kinetically and
      thermodynamically (path B).

PMID- 29338238
TI  - Paralithocins, Antimicrobial Peptides with Unusual Disulfide Connectivity from
      the Red King Crab, Paralithodes camtschaticus.
AB  - As part of an ongoing exploration of marine invertebrates as a source of new
      antimicrobial peptides, hemocyte extracts from the red king crab, Paralithodes
      camtschaticus, were studied. Three cationic cysteine (Cys)-rich peptides, named
      paralithocins 1-3, were isolated by bioassay-guided purification, and their amino
      acid sequences determined by Edman degradation and expressed sequences tag
      analysis. Disulfide bond mapping was performed by high-resolution tandem mass
      spectrometry. The peptides (38-51 amino acids in length) share a unique Cys motif
      composed of eight Cys, forming four disulfide bridges with a bond connectivity of
      (Cys relative position) Cys1-Cys8, Cys2-Cys6, Cys3-Cys5, and Cys4-Cys7, a
      disulfide arrangement that has not been previously reported among antimicrobial
      peptides. Thus, paralithocins 1-3 may be assigned to a previously unknown family
      of antimicrobial peptides within the group of Cys-rich antimicrobial peptides.
      Although none of the isolated peptides displayed antimicrobial activity against
      the target strains Escherichia coli, Pseudomonas aeruginosa, or Staphylococcus
      aureus, they inhibited the growth of several marine bacterial strains with
      minimal inhibitory concentrations in the 12.5-100 MUM range. These findings
      corroborate the hypothesis that marine organisms are a valuable source for
      discovering bioactive peptides with new structural motifs.

PMID- 29338239
TI  - Vinyl Grignard-Mediated Stereoselective Carbocyclization of Lactone Acetals.
AB  - A novel Ferrier-type carbocyclization is reported. It involves a carbohydrate
      derived lactone acetal synthesized from methyl alpha-d-glucopyranoside, which
      upon treatment with excess vinylmagnesium bromide provides a highly substituted
      carbocyclic product as a single stereoisomer. The yield is greatly increased when
      N,N,N',N'-tetramethylethylenediamine is added to the reaction mixture. Optimized
      reaction conditions have been applied to lactone acetals derived from other
      carbohydrates. Based on the obtained results, a possible reaction mechanism has
      been proposed. Furthermore, scalability of the reaction up to 15 g scale and
      derivatization of the carbocyclic product has been demonstrated, including the
      formation of a rare trans-bicyclo[4.3.0]nonene scaffold via a ring-closing
      metathesis. The structure of this and all carbocyclic products were confirmed by
      X-ray crystallographic analysis.

PMID- 29338240
TI  - BiKi Life Sciences: A New Suite for Molecular Dynamics and Related Methods in
      Drug Discovery.
AB  - In this paper, we introduce the BiKi Life Sciences suite. This software makes it
      easy for computational medicinal chemists to run ad hoc molecular dynamics
      protocols in a novel and task-oriented environment; as a notebook, BiKi (acronym
      of Binding Kinetics) keeps memory of any activity together with dependencies
      among them. It offers unique accelerated protein-ligand binding/unbinding methods
      and other useful tools to gain actionable knowledge from molecular dynamics
      simulations and to simplify the drug discovery process.

PMID- 29338241
TI  - Characterization of Macrophage Endogenous S-Nitrosoproteome Using a Cysteine
      Specific Phosphonate Adaptable Tag in Combination with TiO2 Chromatography.
AB  - Protein S-nitrosylation is a cysteine post-translational modification mediated by
      nitric oxide. An increasing number of studies highlight S-nitrosylation as an
      important regulator of signaling involved in numerous cellular processes. Despite
      the significant progress in the development of redox proteomic methods,
      identification and quantification of endogeneous S-nitrosylation using high
      throughput mass-spectrometry-based methods is a technical challenge because this
      modification is highly labile. To overcome this drawback, most methods induce S
      nitrosylation chemically in proteins using nitrosylating compounds before
      analysis, with the risk of introducing nonphysiological S-nitrosylation. Here we
      present a novel method to efficiently identify endogenous S-nitrosopeptides in
      the macrophage total proteome. Our approach is based on the labeling of S
      nitrosopeptides reduced by ascorbate with a cysteine specific phosphonate
      adaptable tag (CysPAT), followed by titanium dioxide (TiO2) chromatography
      enrichment prior to nLC-MS/MS analysis. To test our procedure, we performed a
      large-scale analysis of this low-abundant modification in a murine macrophage
      cell line. We identified 569 endogeneous S-nitrosylated proteins compared with
      795 following exogenous chemically induced S-nitrosylation. Importantly, we
      discovered 579 novel S-nitrosylation sites. The large number of identified
      endogenous S-nitrosylated peptides allowed the definition of two S-nitrosylation
      consensus sites, highlighting protein translation and redox processes as key S
      nitrosylation targets in macrophages.

PMID- 29338242
TI  - In-Situ Biocatalytic Production of Trehalose with Autoinduction Expression of
      Trehalose Synthase.
AB  - We developed an in-situ biocatalytic process that couples autoinduction
      expression of trehalose synthase (TreS) and whole-cell catalysis for trehalose
      production. With lactose as the autoinducer, the activity of recombinant TreS in
      recombinant Escherichia coli was optimized through a visualization method, which
      resulted in a maximum value of 12 033 +/- 730 U/mL in pH-stat fed-batch
      fermentation mode. Meanwhile, the permeability of the autoinduced E. coli
      increased significantly, which makes it possible to be directly used as a whole
      cell biocatalyst for trehalose production, whereby the byproduct glucose can also
      act as an extra carbon source. In this case, the final yield of trehalose was
      improved to 90.5 +/- 5.7% and remained as high as 83.2 +/- 5.0% at the 10th
      batch, which is the highest value achieved using recombinant TreS. Finally, an
      integrated strategy for trehalose production was established, and its advantages
      compared to the traditional mode have been summarized.

PMID- 29338243
TI  - Metadynamics Enhanced Markov Modeling of Protein Dynamics.
AB  - Enhanced sampling techniques represent a versatile approach to account for rare
      conformational transitions in biomolecules. A particularly promising strategy is
      to combine massive parallel computing of short molecular dynamics (MD)
      trajectories (to sample the free energy landscape of the system) with Markov
      state modeling (to rebuild the kinetics from the sampled data). To obtain well
      distributed initial structures for the short trajectories, it is proposed to
      employ metadynamics MD, which quickly sweeps through the entire free energy
      landscape of interest. Being only used to generate initial conformations, the
      implementation of metadynamics can be simple and fast. The conformational
      dynamics of helical peptide Aib9 is adopted to discuss various technical issues
      of the approach, including metadynamics settings, minimal number and length of
      short MD trajectories, and the validation of the resulting Markov models. Using
      metadynamics to launch some thousands of nanosecond trajectories, several Markov
      state models are constructed that reveal that previous unbiased MD simulations of
      in total 16 MUs length cannot provide correct equilibrium populations or
      qualitative features of the pathway distribution of the short peptide.

PMID- 29338244
TI  - Synthesis and Reaction of ortho-Benzoquinone Monohemiaminals.
AB  - The preparation and reactions of ortho-benzoquinone monohemiaminals are
      described. The oxidative dearomatization of phenols bearing amino alcohol groups
      induced N-cyclization to afford ortho-benzoquinone monohemiaminals. The N
      cyclization stereoselectively affords the product when a chiral amino alcohol is
      used as the substituent. The chiral ortho-benzoquinone monohemiaminal undergoes
      stereoselective Diels-Alder reactions with electron-deficient alkenes, as
      expected, confirming the promising utility of ortho-benzoquinone monohemiaminals.

PMID- 29338245
TI  - One-Pot Synthesis of Benzo[b][1,4]oxazins via Intramolecular Trapping Iminoenol.
AB  - A highly atom-efficient "one-pot" protocol has been developed to construct
      multisubstituted 2-hydroxy-benzo[b][1,4]oxazins starting from N-(2
      hydroxylaryl)enaminones. This procedure comprises a PIDA-mediated intramolecular
      iminoenol tautomer trapping reaction, followed by Et3N-promoted aerobic oxidative
      ring construction. In particular, an O2 molecule from air served as the oxygen
      source of the hydroxyl group in the titled products. This reaction proceeded
      smoothly at room temperature under air atmosphere and metal-free conditions.

PMID- 29338246
TI  - Non-Transition-Metal Catalytic System for N2 Reduction to NH3: A Density
      Functional Theory Study of Al-Doped Graphene.
AB  - The prevalent catalysts for natural and artificial N2 fixation are known to hinge
      upon transition-metal (TM) elements. Herein, we demonstrate by density functional
      theory that Al-doped graphene is a potential non-TM catalyst to convert N2 to NH3
      in the presence of relatively mild proton/electron sources. In the integrated
      structure of the catalyst, the Al atom serves as a binding site and catalytic
      center while the graphene framework serves as an electron buffer during the
      successive proton/electron additions to N2 and its various downstream NxHy
      intermediates. The initial hydrogenation of N2 can readily take place via an
      internal H-transfer process with the assistance of a Li+ ion as an additive. In
      view of the recurrence of H transfer in the first step of N2 reduction observed
      in biological nitrogenases and other synthetic catalysts, this finding highlights
      the significance of heteroatom-assisted H transfer in the design of synthetic
      catalysts for N2 fixation.

PMID- 29338247
TI  - Lattice Models of Bacterial Nucleoids.
AB  - Mesoscale molecular modeling is providing a new window into the inner workings of
      living cells. Modeling of genomes, however, remains a technical challenge, due to
      their large size and complexity. We describe a lattice method for rapid
      generation of bacterial nucleoid models that integrates experimental data from a
      variety of biophysical techniques and provides a starting point for simulation
      and hypothesis generation. The current method builds models of a circular
      bacterial genome with supercoiled plectonemes, packed within the small space of
      the bacterial cell. Lattice models are generated for Mycoplasma genitalium and
      Escherichia coli nucleoids, and used to simulate interaction data. The method is
      rapid enough to allow generation of multiple models when analyzing
      structure/function relationships, and we demonstrate use of the lattice models in
      creation of an all-atom representation of an entire cell.

PMID- 29338248
TI  - Catalytic Oligopeptide Synthesis.
AB  - Waste-free catalytic assembly of alpha-amino acids is fueled by a multiboron
      catalyst that features a characteristic B3NO2 heterocycle, providing a versatile
      catalytic protocol wherein functionalized natural alpha-amino acid units are
      accommodated and commonly used protecting groups are tolerated. The facile
      dehydrative conditions eliminate the use of engineered peptide coupling reagents,
      exemplifying a greener catalytic alternative for peptide coupling. The catalysis
      is sufficiently robust to enable pentapeptide synthesis, constructing all four
      amide bond linkages in a catalytic fashion.

PMID- 29338249
TI  - Highly Sensitive and Wearable In2O3 Nanoribbon Transistor Biosensors with
      Integrated On-Chip Gate for Glucose Monitoring in Body Fluids.
AB  - Nanoribbon- and nanowire-based field-effect transistor (FET) biosensors have
      stimulated a lot of interest. However, most FET biosensors were achieved by using
      bulky Ag/AgCl electrodes or metal wire gates, which have prevented the biosensors
      from becoming truly wearable. Here, we demonstrate highly sensitive and conformal
      In2O3 nanoribbon FET biosensors with a fully integrated on-chip gold side gate,
      which have been laminated onto various surfaces, such as artificial arms and
      watches, and have enabled glucose detection in various body fluids, such as sweat
      and saliva. The shadow-mask-fabricated devices show good electrical performance
      with gate voltage applied using a gold side gate electrode and through an aqueous
      electrolyte. The resulting transistors show mobilities of ~22 cm2 V-1 s-1 in 0.1*
      phosphate-buffered saline, a high on-off ratio (105), and good mechanical
      robustness. With the electrodes functionalized with glucose oxidase, chitosan,
      and single-walled carbon nanotubes, the glucose sensors show a very wide
      detection range spanning at least 5 orders of magnitude and a detection limit
      down to 10 nM. Therefore, our high-performance In2O3 nanoribbon sensing platform
      has great potential to work as indispensable components for wearable healthcare
      electronics.

PMID- 29338250
TI  - Pickering Emulsion Formation of Paraffin Wax in an Ethanol-Water Mixture
      Stabilized by Primary Polymer Particles and Wax Microspheres Thereof.
AB  - Stable dispersions of paraffin wax droplets and their nano- and microspheres have
      broad applications. Despite intensive efforts, the production of uniform wax
      spheres remains a challenge. For their preparation, abundant surfactants and
      other additives are commonly used to stabilize the dispersions. These additives
      are hardly removable and entrain often adverse consequence in many applications,
      particularly in biological and medical applications, where microspheres with
      absolutely clean surface are preferred. We report here a novel process to prepare
      stable dispersion of wax droplets in a water-ethanol mixture with a narrow size
      distribution by simply shaking without any surfactants. The process is featured
      by using primary polymer particles (PPs) of poly(dodecene-trihydroxymethylpropane
      triacrylate) as a Pickering stabilizer. PPs were prepared by precipitation
      polymerization without any surfactant and stabilizer. By rapidly cooling the wax
      emulsion, solid wax spheres with good uniformity were obtained. Their size,
      between 50 and 480 MUm, was easily adjustable by changing the shaking rate,
      number of PPs, and particularly the size of PPs. The morphology of the wax
      spheres was examined by SEM, which showed that they were covered by a layer of
      PPs. The formation mechanism of the microspheres was also discussed on the basis
      of the adsorption energy of PPs on wax spheres, estimated from the corresponding
      contact angle of the solvent toward the PPs and the wax. This paper presents a
      novel pathway for the preparation of wax microspheres with only polymer particles
      without the need for any other additives.

PMID- 29338251
TI  - Delivery of Oxytocin to the Brain for the Treatment of Autism Spectrum Disorder
      by Nasal Application.
AB  - Oxytocin (OXT) is a cyclic nonapeptide, two amino acids of which are cysteine,
      forming an intramolecular disulfide bond. OXT is produced in the hypothalamus and
      is secreted into the bloodstream from the posterior pituitary. As recent studies
      have suggested that OXT is a neurotransmitter exhibiting central effects
      important for social deficits, it has drawn much attention as a drug candidate
      for the treatment of autism. Although human-stage clinical trials of the nasal
      spray of OXT for the treatment of autism have already begun, few studies have
      examined the pharmacokinetics and brain distribution of OXT after nasal
      application. The aim of this study is to evaluate the disposition, nasal
      absorption, and therapeutic potential of OXT after nasal administration. The
      pharmacokinetics of OXT after intravenous bolus injection to rats followed a two
      compartment model, with a rapid initial half-life of 3 min. The nasal
      bioavailability of OXT was approximately 2%. The brain concentration of OXT after
      nasal application was much higher than that after intravenous application,
      despite much lower concentrations in the plasma. More than 95% of OXT in the
      brain was directly transported from the nasal cavity. The in vivo stress-relief
      effect by OXT was observed only after intranasal administration. These results
      indicate that pharmacologically active OXT was effectively delivered to the brain
      after intranasal administration. In conclusion, the nasal cavity is a promising
      route for the efficient delivery of OXT to the brain.

PMID- 29338252
TI  - Orychophragines A-C, Three Biologically Active Alkaloids from Orychophragmus
      violaceus.
AB  - Orychophragines A-C (1-3), three new alkaloids with an novel 2-piperazinone-fused
      2,4-dioxohexahydro-1,3,5-triazine skeleton, were isolated from the seeds of
      Orychophragmus violaceus. Their structures were established on the basis of
      spectroscopic analysis and X-ray crystallographic analysis. Orychophragines A (1)
      exhibited remarkable cytotoxicity against HepG2, A549, Hela, and HCT-116 cells
      with IC50 values of 7.73, 10.79, 11.91, and 9.93 MUM, respectively.
      Orychophragines C (3) showed moderate 60Co gamma radiation protection activity in
      HUVEC cells. A plausible biosynthetic pathway for 1-3 was proposed.

PMID- 29338253
TI  - Correction to Highly Efficient Retention of Polysulfides in "Sea-Urchin"-Like
      Carbon Nanotube/Nanopolyhedra Superstructures as Cathode Material for Ultralong
      Life Lithium-Sulfur Batteries.

PMID- 29338254
TI  - Editorial 2018.

PMID- 29338255
TI  - To Be Fibrils or To Be Nanofilms? Oligomers Are Building Blocks for Fibril and
      Nanofilm Formation of Fragments of Abeta Peptide.
AB  - To identify the key stages in the amyloid fibril formation we studied the
      aggregation of amyloidogenic fragments of Abeta peptide, Abeta(16-25), Abeta(31
      40), and Abeta(33-42), using the methods of electron microscopy, X-ray analysis,
      mass spectrometry, and structural modeling. We have found that fragments Abeta(31
      40) and Abeta(33-42) form amyloid fibrils in the shape of bundles and ribbons,
      while fragment Abeta(16-25) forms only nanofilms. We are the first who performed
      2D reconstruction of amyloid fibrils by the Markham rotation technique on
      electron micrographs of negatively stained fragments of Abeta peptide. Combined
      analysis of the data allows us to speculate that both the fibrils and the films
      are formed via association of ring-shaped oligomers with the external diameter of
      about 6 to 7 nm, the internal diameter of 2 to 3 nm, and the height of ~3 nm. We
      conclude that such oligomers are the main building blocks in fibrils of any
      morphology. The interaction of ring oligomers with each other in different ways
      makes it possible to explain their polymorphism. The new mechanism of
      polymerization of amyloidogenic proteins and peptides, described here, could
      stimulate new approaches in the development of future therapeutics for the
      treatment of amyloid-related diseases.

PMID- 29338256
TI  - Palladium-Catalyzed Four-Component Cascade Reaction for the Synthesis of Highly
      Functionalized Acyclic O,O-Acetals.
AB  - A palladium-catalyzed four-component cascade reaction of carbon dioxide, amines,
      allenyl ethers, and aryl iodides has been developed for the first time. The novel
      reaction allows simultaneous construction of three different new bonds (C-N, C-O,
      and C-C) in a single step, affording an efficient method for the synthesis of a
      variety of highly functionalized acyclic O,O-acetals. Excellent chemo- and
      regioselectivity, wide substrate scope, and good functional group tolerance are
      features of the method.

PMID- 29338257
TI  - A Dynamic Protein-Protein Coupling between the TonB-Dependent Transporter FhuA
      and TonB.
AB  - Bacterial outer membrane TonB-dependent transporters function by executing cycles
      of binding and unbinding to the inner membrane protein TonB. In the vitamin B12
      transporter BtuB and the ferric citrate transporter FecA, substrate binding
      increases the periplasmic exposure of the Ton box, an energy-coupling segment.
      This increased exposure appears to enhance the affinity of the transporter for
      TonB. Here, continuous wave and pulse EPR spectroscopy were used to examine the
      state of the Ton box in the Escherichia coli ferrichrome transporter FhuA. In its
      apo state, the Ton box of FhuA samples a broad range of positions and multiple
      conformational substates. When bound to ferrichrome, the Ton box does not extend
      further into the periplasm, although the structural states sampled by the FhuA
      Ton box are altered. When bound to a soluble fragment of TonB, the TonB-FhuA
      complex remains heterogeneous and dynamic, indicating that TonB does not make
      strong, specific contacts with either the FhuA barrel or the core region of the
      transporter. This result differs from that seen in the crystal structure of the
      TonB-FhuA complex. These data indicate that unlike BtuB and FecA, the periplasmic
      exposure of the Ton box in FhuA does not change significantly in the presence of
      substrate and that allosteric control of transporter-TonB interactions functions
      by a different mechanism than that seen in either BtuB or FecA. Moreover, the
      data indicate that models involving a rotation of TonB relative to the
      transporter are unlikely to underlie the mechanism that drives TonB-dependent
      transport.

PMID- 29338258
TI  - Nanoparticle-Cell Interactions: Surface Chemistry Effects on the Cellular Uptake
      of Biocompatible Block Copolymer Assemblies.
AB  - The development of nanovehicles for intracellular drug delivery is strongly bound
      to the understating and control of nanoparticles cellular uptake process, which
      in turn is governed by surface chemistry. In this study, we explored the
      synthesis, characterization, and cellular uptake of block copolymer assemblies
      consisting of a pH-responsive poly[2-(diisopropylamino)ethyl methacrylate] (PDPA)
      core stabilized by three different biocompatible hydrophilic shells (a
      zwitterionic type poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) layer, a
      highly hydrated poly(ethylene oxide) (PEO) layer with stealth effect, and an also
      proven nontoxic and nonimmunogenic poly(N-(2-hydroxypropyl)methacrylamide)
      (PHPMA) layer). All particles had a spherical core-shell structure. The largest
      particles with the thickest hydrophilic stabilizing shell obtained from PMPC40-b
      PDPA70 were internalized to a higher level than those smaller in size and
      stabilized by PEO or PHPMA and produced from PEO122-b-PDPA43 or PHPMA64-b-PDPA72,
      respectively. Such a behavior was confirmed among different cell lines, with
      assemblies being internalized to a higher degree in cancer (HeLa) as compared to
      healthy (Telo-RF) cells. This fact was mainly attributed to the stronger binding
      of PMPC to cell membranes. Therefore, cellular uptake of nanoparticles at the sub
      100 nm size range may be chiefly governed by the chemical nature of the
      stabilizing layer rather than particles size and/or shell thickness.

PMID- 29338260
TI  - Seco-Dendrobine-Type Alkaloids and Bioactive Phenolics from Dendrobium
      findlayanum.
AB  - Investigation of the 95% EtOH extract of stems of Dendrobium findlayanum afforded
      four new seco-dendrobines, findlayines A-D (1-4); two known dendrobines,
      dendrobine (5) and 2-hydroxydendrobine (6); and four new phenolic compounds,
      dendrofindlaphenols A-C (7, 9, and 10) and 6"-de-O-methyldendrofindlaphenol A
      (8). Compounds 1 and 2 are the first seco-dendrobines possessing a seven-membered
      lactam moiety, with 3 and 4 derived from the oxidative cleavage of the C-2-C-3
      bond of dendrobine. The structures were established using spectroscopic methods
      and by comparison with literature data. The absolute configurations of 1-4 were
      confirmed via single-crystal X-ray diffraction data. Cytotoxic activity assays
      against HL-60, SMMC-7721, A-549, MCF-7, and SW480 human cancer cell lines
      revealed IC50 values ranging from 2.3 to 5.3 MUM for compound 7, from 19.4 to
      34.4 MUM for 8, and from 49.4 to 96.8 MUg/mL for the EtOAc extract. An assay of
      the inhibition of NO production with RAW 264.7 cells indicated that 8 had an IC50
      value of 21.4 MUM, and the EtOAc extract, 10.5 MUg/mL. The EtOAc extract
      possessed DPPH radical scavenging activity of 69.93% at 100 MUg/mL.

PMID- 29338261
TI  - Nature of the Three-Electron Bond.
AB  - We analyze the properties of 15 3-electron bonds, which include sigma-3-electron
      bonds, such as dihalide radical anions and di-noble gas radical cations, pi-3
      electron-bonds as in hydrazine radical cations, and doubly-pi-(3e)-bonded species
      such as O2, FeO+, S2, etc. The primary analytical tool is the breathing-orbital
      valence-bond (BOVB) method, which enables us to quantify the charge shift
      resonance energy (RECS) of the three electrons, and the bond dissociation
      energies (De). BOVB is tested reliable against MRCI calculations. Our findings
      show that in all 3-electron bonds, none of the VB structures have by themselves
      any bonding. In fact, in each VB structure, the three electrons maintain Pauli
      repulsion, while the entire bonding energy arises from resonance due to the
      charge shift between the two or more constituent VB structures. Hence, 3e-bonds
      are charge shift bonds (CSBs). The CSB character is probed by calculating the
      Laplacian (L) of the 3e-bond. Thus, much like the CSBs in electron-pair bonds,
      such as F2 or the central bond in [1.1.1]propellane, here too L is positive, thus
      showing the excess kinetic energy of the shared density due to the Pauli
      repulsion in the 3-electron VB structures. The RECS values for 3-electron bonds
      are invariably larger than the corresponding bond energies. For the doubly-pi
      (3e)-bonded species, RECS is very large, exceeding 100 kcal mol-1. As such, it is
      fitting to conclude that sigma- and pi-3-electron-bonds find their natural place
      in the CSB family along with two-electron CSBs, with which they share identical
      energetic and topological characteristics. Experimental manifestations/tests of
      3e-CSBs are proposed.

PMID- 29338262
TI  - Roasted Barley Extract Affects Blood Flow in the Rat Tail and Increases Cutaneous
      Blood Flow and Skin Temperature in Humans.
AB  - Roasted barley extract (RBE, "Mugicha") is a traditional Japanese beverage
      reported to improve blood viscosity and affect food functionality. RBE is
      suggested to contain 2,5-diketopiperazines, which are the functional component
      with neuroprotective and immunostimulatory effects that are produced in food
      through roasting. In this study, we investigated the effects of RBE on blood
      circulation, both clinically and in rats. At first, we confirmed five 2,5
      diketopiperazine derivatives in RBE by LC-MS analysis. Secondarily, we revealed
      that RBE affects blood flow in the rat tail and compared the efficacy on rat tail
      blood flow among five 2,5-diketopiperazines in RBE. Especially, cyclo(d-Phe-l
      Pro) was the most effective in increasing blood flow in the rat tail. We also
      researched the mechanism of cyclo(d-Phe-l-Pro) with rat aorta study. As a result,
      we confirmed that cyclo(d-Phe-l-Pro) has an effect on vasodilatation through the
      release of nitric oxide in the vascular endothelium. Finally, we also confirmed
      that RBE affects cutaneous blood flow and increases skin temperature in humans.

PMID- 29338263
TI  - Use of a Promiscuous Glycosyltransferase from Bacillus subtilis 168 for the
      Enzymatic Synthesis of Novel Protopanaxatriol-Type Ginsenosides.
AB  - Ginsenosides are the principal bioactive ingredients of Panax ginseng and possess
      diverse notable pharmacological activities. UDP-glycosyltransferase (UGT)
      mediated glycosylation of the C6-OH and C20-OH of protopanaxatriol (PPT) is the
      prominent biological modification that contributes to the immense structural and
      functional diversity of PPT-type ginsenosides. In this study, the glycosylation
      of PPT and PPT-type ginsenosides was achieved using a promiscuous
      glycosyltransferase (Bs-YjiC) from Bacillus subtilis 168. PPT was selected as the
      probe for the in vitro glycodiversification of PPT-type ginsenosides using
      diverse UDP-sugars as sugar donors. Structural analysis of the newly
      biosynthesized products demonstrated that Bs-YjiC can transfer a glucosyl moiety
      to the free C3-OH, C6-OH, and C12-OH of PPT. Five PPT-type ginsenosides were
      biosynthesized, including ginsenoside Rh1 and four unnatural ginsenosides. The
      present study suggests flexible microbial UGTs play an important role in the
      enzymatic synthesis of novel ginsenosides.

PMID- 29338264
TI  - Quantum Interference Contribution to the Dipole Moment of Diatomic Molecules.
AB  - The interference energy partitioning analysis method developed by our group and
      used to study the nature of the chemical bond was extended to partition the
      electric dipole moment in quasi-classical and interference contributions. Our
      results show that interference participates in charge displacement in polar
      molecules, providing, directly or indirectly, a relevant contribution for the
      total dipole moment. A linear correlation was found between the interference
      contribution of the dipole moment from the bond electron group, MUINT(bond), and
      the difference of electronegativity of the atoms which form the bond, DeltaXAB.
      This interesting result reinforces the fact that electronegativity is not a
      property of an atom alone, but rather a property of the atom in the molecule and
      that DeltaXAB can only be associated with that part of the total charge
      displacement resulting from the formation of the chemical bond. The partitioning
      of the total dipole moment into quasi-classical and interference contributions
      provides new insights about the reasons for the failure of the DeltaXAB criterion
      in predicting the correct orientation of the dipole moment in several molecules.
      The results of the present work also bring additional evidence for the previously
      proposed mechanism of formation of polar bonds.

PMID- 29338265
TI  - Controlling Polyelectrolyte Adsorption onto Carbon Nanotubes by Tuning Ion-Image
      Interactions.
AB  - Understanding and controlling polyelectrolyte adsorption onto carbon nanotubes is
      a fundamental challenge in nanotechnology. Polyelectrolytes have been shown to
      stabilize nanotube suspensions through adsorbing onto the nanotube surface, and
      polyelectrolyte-coated nanotubes are emerging as building blocks for complex and
      addressable self-assembly. Conventional wisdom suggests that polyelectrolyte
      adsorption onto nanotubes is driven by specific chemical or van der Waals
      interactions. We develop a simple mean-field model and show that ion-image
      attraction significantly effects adsorption onto conducting nanotubes at low salt
      concentrations. Our theory suggests a simple strategy to selectively and
      reversibly functionalize carbon nanotubes on the basis of their electronic
      structures, which in turn modify the ion-image attraction.

PMID- 29338266
TI  - All-Solid-State Batteries with Thick Electrode Configurations.
AB  - We report the preparation of thick electrode all-solid-state lithium-ion cells in
      which a large geometric capacity of 15.7 mAh cm-2 was achieved at room
      temperature using a 600 MUm-thick cathode layer. The effect of ionic conductivity
      on the discharge performance was then examined using two different materials for
      the solid electrolyte. Furthermore, important morphological information regarding
      the tortuosity factor was electrochemically extracted from the capacity-current
      data. The effect of tortuosity on cell performance was also quantitatively
      discussed.

PMID- 29338267
TI  - Theory for the Liquid-Liquid Phase Separation in Aqueous Antibody Solutions.
AB  - This study presents the theory for liquid-liquid phase separation for systems of
      molecules modeling monoclonal antibodies. Individual molecule is depicted as an
      assembly of seven hard spheres, organized to mimic the Y-shaped antibody. We
      consider the antibody-antibody interactions either through Fab, Fab' (two Fab
      fragments may be different), or Fc domain. Interaction between these three
      domains of the molecule (hereafter denoted as A, B, and C, respectively) is
      modeled by a short-range square-well attraction. To obtain numerical results for
      the model under study, we adapt Wertheim's thermodynamic perturbation theory. We
      use this model to calculate the liquid-liquid phase separation curve and the
      second virial coefficient B2. Various interaction scenarios are examined to see
      how the strength of the site-site interactions and their range shape the
      coexistence curve. In the asymmetric case, where an attraction between two sites
      is favored and the interaction energies for the other sites kept constant,
      critical temperature first increases and than strongly decreases. Some more
      microscopic information, for example, the probability for the particular two
      sites to be connected, has been calculated. Analysis of the experimental liquid
      liquid phase diagrams, obtained from literature, is presented. In addition, we
      calculate the second virial coefficient under conditions leading to the liquid
      liquid phase separation and present this quantity on the graph B2 versus protein
      concentration.

PMID- 29338268
TI  - Predicting Surface Tensions of Surfactant Solutions from Statistical Mechanics.
AB  - The importance of surfactants to various industries necessitates a predictive
      understanding of their surface tension and adsorption behavior in terms of
      molecular characteristics. Previous models are highly empirical, require fitting
      parameters, and have limited applicability at various temperatures. Here, we
      provide a surface tension model based on statistical mechanics that (1) is
      thermodynamically consistent, (2) provides a higher predictive power, wherein
      surface tension can be calculated for any tail length, concentration, and
      temperature from molecular parameters, and (3) provides a physical understanding
      of the important molecular interactions at play. This model is applicable to both
      nonionic and ionic surfactants, where the effects of the electric double layer
      have been taken into account in the latter case. For nonionic surfactants, we
      were able to extend our model to predict dynamic surface tension as well. We have
      validated our model with tensiometry experiments for various surfactants,
      concentrations, and temperatures. In addition, we have validated our model with a
      diverse set of literature data, wherein agreement within a few mN M-1 and a
      correct prediction of phase change behavior is shown. The model could enable a
      more informed design of surfactant systems and serve as the theoretical basis for
      theory on more complex surfactant systems such as mixtures.

PMID- 29338269
TI  - Reactivity Toward Ag+: A General Strategy to Generate a New Emissive Center from
      NIR-Emitting Gold Nanoparticles.
AB  - We report a facile strategy for the transformation of single NIR-emitting AuNPs
      to dual-NIR-emitting bimetallic Ag@AuNPs based on the robust reactivity toward
      Ag(I) ions under mild conditions. The reactivities toward Ag(I) ions were found
      to be significantly different between visible- and NIR-emitting glutathione (GSH)
      coated AuNPs: the high GSH surface coverage on the 610 nm-emitting AuNPs resulted
      in a reversible interaction due to enough surface steric hindrance to resist
      Ag(I) ions from interaction with the Au(0) core, whereas the low GSH surface
      coverage on the 810 nm-emitting AuNPs led to both antigalvanic reaction and Ag(I)
      carboxylate shell formation on the surface of the AuNPs, which were responsible
      for the formation of a new emissive center at 705 nm. This strategy was also
      demonstrated to exhibit excellent generalization toward various NIR-emitting
      AuNPs with surface chemistries containing carboxyl groups, opening a new pathway
      of tailoring the optical properties of metallic NPs through surface reactivity.

PMID- 29338270
TI  - Effect of calcium on the microstructure and corrosion behavior of microarc
      oxidized Mg-xCa alloys.
AB  - Magnesium alloys are potential biodegradable implants for biomedical
      applications, and calcium (Ca) is one kind of ideal element being examined for
      magnesium alloys and biodegradable ceramic coatings owing to its biocompatibility
      and mechanical suitability. In this study, microarc oxidation (MAO) coatings were
      prepared on Mg-xCa alloys to study the effect of Ca on the microstructure and
      corrosion resistance of Mg-xCa alloys and their surface MAO coatings. The
      electrochemical corrosion behavior was investigated using an electrochemical
      workstation, and the degradability and bioactivity were evaluated by soaking
      tests in simulated body fluid (SBF) solutions. The corrosion products were
      characterized by scanning electron microscopy, x-ray diffractometry, and Fourier
      transform infrared spectrometry. The effects of Ca on the alloy phase
      composition, microstructure, MAO coating formation mechanism, and corrosion
      behavior were investigated. Results showed that the Mg-0.82Ca alloy and MAO
      coated Mg-0.82Ca exhibited the highest corrosion resistance. The number and
      distribution of Mg2Ca phases can be controlled by adjusting the Ca content in the
      Mg-xCa alloys. The proper amount of Ca in magnesium alloy was about 0.5-0.8 wt.
      %. The pore size, surface roughness, and corrosion behavior of microarc oxidized
      Mg-xCa samples can be controlled by the number and distribution of the Mg2Ca
      phase. The corrosion behaviors of microarc oxidized Mg-Ca in SBF solutions were
      discussed.

PMID- 29338271
TI  - Analytical, anthropometric and dietary factors associated with the development of
      fibrosis in patients with nonalcoholic fatty liver disease.
AB  - BACKGROUND: a prolonged non-alcoholic steatohepatitis (NASH) condition can lead
      to advanced stages of liver disease and the development of hepatocellular
      carcinoma. AIM: to evaluate analytical, anthropometric and dietary factors
      associated with the presence of fibrosis as this is the factor that most
      influences survival and evolution. METHODS: seventy-six patients with liver
      biopsy-diagnosed non-alcoholic fatty liver disease (NAFLD) were included.
      Biopsies were scored considering the NASH criteria of Kleiner. Analytical,
      anthropometric and dietary (survey) parameters were obtained. NAFLD-FS is a non
      invasive fibrosis index and was assessed for each patient. Leptin, adiponectin,
      resistin and TNF-alpha serum levels were determined. RESULTS: fifty-six patients
      were male (73.7%) and the mean age was 44.5 +/- 11.3 years of age (19-68). Thirty
      nine (51.3%) (F1-F2: 84.6%; F3-4: 15.4%) patients had fibrosis in the liver
      biopsy. Seventeen females (85%) had fibrosis versus 22 males (39%), which was
      statistically significant by univariate analysis (p < 0.01). Patients with
      advanced fibrosis were older, with lower platelet counts, lower serum albumin,
      greater homeostatic model assessment insulin resistance (HOMA-IR), lower dietary
      lipids percentage, higher serum leptin levels and higher NAFLD Fibrosis Score
      (NAFLD-FS) values. This index had a negative predictive value of 98% and a
      positive predictive value of 60% for the detection of fibrosis. Variables
      independently associated with fibrosis (logistic regression) included male gender
      (protective factor) (0.09, 95% CI 0.01-0.7; p < 0.05) and HOMA-IR (1.7, 95% CI,
      1.03-2.79; p < 0.05). CONCLUSIONS: gender and HOMA-IR were the only independent
      factors associated with fibrosis. NAFLD-FS could be considered as an accurate
      scoring system to rule out advanced fibrosis.

PMID- 29338272
TI  - Morphologic assessment of mandibular anterior teeth root canal using CBCT.
AB  - OBJECTIVE: The aim of this study was to evaluate the number and morphological
      characteristics of the roots and root canals in mandibular anterior teeth, using
      cone beam computed tomography. METHODS AND MATERIALS: In this cross-sectional
      study, 1053 anterior mandibular teeth from 200 CBCT scans were evaluated. The
      teeth were completely developed and should have had no fillings in the root or
      crown. The teeth were investigated in terms of the number of roots and root
      canals, the location of the apical foramen, the distance of the apical foramen to
      the anatomical apex, root length, crown length, dilacerations and the type of
      canals according to Vertucci's classification. RESULTS: 87.9% of teeth had one
      root canal and of all of the teeth, three canines (0.3%) were found that had two
      roots. In 80.3% (n: 848) of cases the foramen apical location was central, then
      the buccal (9.3%), lingual (3.9%), distal (3.8%), and mesial (2.7%). The type of
      root canals, according to Vertucci's classification, with respect to prevalence,
      included type I (88.2%), type III (8.1%), type II (3.3%), type V (0.3%), and type
      VI (0.1%), respectively. In terms of the characteristics investigated, bilateral
      symmetry was observed. Dilaceration was not seen in any of the teeth. CONCLUSION:
      The root canal morphology of mandibular anterior teeth has great diversity that
      may differ between different races, and should be considered by all dentists in
      order to achieve the best dental treatment.

PMID- 29338273
TI  - Adverse drug reactions of non-opioid and opioid analgesics reported to Croatian
      national authority from 2007 to 2014.
AB  - OBJECTIVE: Adverse drug reactions (ADRs) are commonly observed in the health
      services because of system weaknesses and individual errors. Analgesics are
      widely used and it can be expected that with the increased use one can expect
      increased number of ADRs of analgesics. The aim of this study was to analyze ADRs
      of non-opioid and opioid analgesics reported to the Croatian Agency for Medicinal
      Products and Medical Devices (HALMED) from 2007 to 2014. METHODS: HALMED provided
      data on generic drug name, year of the ADR report, type of report, institution,
      reporting person, patient's age, sex and ADR type. RESULTS: In the analyzed
      period 796 ADRs of analgesics were reported, of which 367 (46%) were serious
      ADRs. Number of ADR reports was continuously increasing during the analyzed
      period. There were 20 analgesics that had >=5 reports, making 597 (75%) of all
      ADR reports for analgesics. The most common adverse reaction reports of those 20
      analgesics referred to individual drugs (n=16; 80%). Most of the ADR reports were
      filed by physicians (n=257; 43%), followed by pharmacists (n=252; 42%). Most side
      effects (n=572; 96%) were reported spontaneously through appropriate forms by
      patients or health professionals. ADRs were most commonly reported in women
      (n=352; 59%) and most of them have occurred in adults (n=354; 59%). The most
      common ADRs of opioid and non-opioid analgesics have been reported on the skin
      and mucous membranes. Most serious ADRs were result of action of opioid
      analgesics. CONCLUSION: Number of ADR reports in Croatia is continuously
      increasing and a considerable number of them refers to serious ADRs. To keep
      better track of medications and ADRs it is necessary to educate and encourage
      health professionals and patients in reporting side effects.

PMID- 29338274
TI  - Frequency and correlation of lip prints, fingerprints and ABO blood groups in
      population of Sriganganagar District, Rajasthan.
AB  - OBJECTIVE: To investigate the frequency and uniqueness of different lip print
      patterns, fingerprint patterns in relation to gender and ABO Rh blood groups
      among a semi-urban population of Sriganganagar, Rajasthan. MATERIALS AND METHODS:
      The study was conducted on 1200 healthy volunteers aged 18-30 years. The
      cheiloscopic and dermatographic data of each subject were obtained and were
      analysed according to the Suzuki and Tsuchihashi and Henry systems of
      classification, respectively. Two forensic experts analyzed the patterns
      independently. The ABO Rh blood group was also recorded for each subject. The Chi
      square statistical analysis was done and tests were considered significant when p
      value <0.001 and Cohen kappa test was applied to analyze inter-observer
      reliability. RESULTS: The B+ blood group was noted as most common in both genders
      while least common were A- among males and AB- in females. Type II lip pattern
      was most predominant while the least common was Type I' in males and Type I' and
      Type V in females. The UL fingerprint pattern was the most common, while RL was
      least noted in both genders. All the fingerprint patterns showed correlation with
      different lip print patterns. A correlation was found between different blood
      groups and lip print patterns except Type I (vertical) lip pattern. A positive
      correlation was observed between all the blood groups and fingerprint patterns,
      except for RL pattern. CONCLUSION: There is an association between lip print
      patterns, fingerprint patterns and ABO blood groups in both the genders. Thus,
      correlating the uniqueness of these physical evidences sometimes helps the
      forensic team members in accurate personal identification or it can at least
      narrow the search for an individual where there are no possible data referring to
      the identity of the subject.

PMID- 29338275
TI  - Metformin use associated with protective effects for ocular complications in
      patients with type 2 diabetes - observational study.
AB  - OBJECTIVE: The aim was to study the association of the use of an oral
      antihyperglycemic agent metformin with the presence of ocular complications in
      patients with type 2 diabetes (T2D). METHODS: Medical records were reviewed for
      234 patients with diagnosed T2D. 81.2% (n=190) patients were using metformin and
      18.8% (n=44) using other oral antihyperglycemic agents. Plasma glucose
      concentration, glycated haemoglobin, and the presence of ocular complications in
      patients treated with metformin were compared to those in patients treated with
      other oral antihyperglycemic agents. RESULTS: Ocular complications occurred in 65
      patients (27.8%). Patients treated with metformin had fewer ocular complications
      compared to patients treated with other oral antihyperglycemic agents
      (chi2=19.985; p<0.0001). After adjustment for gender, age, duration of T2D, serum
      concentration of cholesterol, smoking, body mass index and presence of other
      diseases, treatment with metformin decreased the odds of both glaucoma (OR=0.14,
      95% CI: 0.03-0.57, p=0.006) and diabetic retinopathy (OR=0.33, 95% CI: 0.14-0.82,
      p=0.017) compared with other oral antihyperglycemic agents. CONCLUSION: Our
      results suggest that metformin may have a protective effect on ocular
      complications, especially glaucoma, in patients with T2D. The effects of
      metformin either regarding prevention of ocular complications or ocular
      complications already developed in patients with T2D, should be further
      investigated.

PMID- 29338276
TI  - Evaluation of the water sorption of luting cements in different solutions.
AB  - OBJECTIVE: To evaluate and compare the water sorption of three luting cements in
      three different solutions: distilled water and artificial saliva with different
      pH values (7.4 and 3.0). MATERIALS AND METHODS: Resin-modified glass-ionomer
      cement (GC Fuji Plus) and two resin cements (Multilink Automix and Variolink II)
      were used. A total of 45 specimens - 15 specimens (15x1 mm) for each cement were
      prepared according to ISO standard 4049:2009. The water sorptions of the cements
      were calculated by weighing the specimens before and after immersion and
      desiccation. RESULTS: . Nonparametric statistic methods were applied. GC Fuji
      Plus cement showed significantly higher values of water sorption in all three
      solutions of both resin cements (p<0.009) and significantly higher values of
      sorption in artificial saliva pH 3.0. Multilink Automix showed significantly
      higher values of water sorption compared with Variolink II in artificial saliva
      pH 7.4, and higher values of sorption in this solution compared with pH value
      3.0. CONCLUSION: Water sorption values are mainly influenced by the proportion of
      hydrophilic matrix, the type and composition of filler, and the pH value of
      solutions.

PMID- 29338277
TI  - Assessment of inpatient psychiatric readmission risk among patients discharged on
      an antipsychotic polypharmacy regimen: A retrospective cohort study.
AB  - OBJECTIVE: Patients are frequently prescribed multiple antipsychotic medications,
      leading to higher healthcare costs and increased risk for side effects. The
      efficacy of multiple versus single antipsychotics to prevent acute relapse,
      measured by incidence of inpatient readmission, is investigated in Arizona, USA.
      METHOD: A retrospective chart review compared socio-demographic and clinical data
      from 1,010 patients discharged on a single and 377 discharged on multiple
      antipsychotic medications. Case management records were reviewed for readmission
      within one year of discharge. RESULTS: Younger age, diagnosis of Schizophrenia or
      Schizoaffective Disorder, prescription of mood stabilizer, shorter length of
      stay, and discharge to residential treatment or crisis recovery unit were
      associated with multiple antipsychotics at discharge. Readmission rates of the
      single (13.7%) versus multiple (15.9%) antipsychotic groups were not
      statistically different (p=0.286). Logistic regression analysis established that
      only age (younger) and the prescription of a mood stabilizer at discharge were
      significant predictors for increased risk for readmission (p=0.010 and p=0.049,
      respectively). A Cox survival analysis supported these findings. CONCLUSIONS:
      Concomitant antipsychotic polypharmacy at discharge did not reduce readmission
      risk over a one-year period. Given the increased risk of side effects and
      financial costs of polypharmacy, this study did not provide evidence to support
      this practice. Strikingly, only two variables predicted readmission risk, younger
      age and prescription of mood stabilizer. Although practitioners should follow
      practice guidelines more closely to prevent unnecessary exposure to potentially
      lethal side effects of antipsychotic polypharmacy, further studies are needed to
      better identify patients at high risk for readmission.

PMID- 29338278
TI  - The effects of interprofessional diabetes education on the knowledge of medical,
      dentistry and nursing students.
AB  - OBJECTIVES: Interprofessional teamwork is best attained through education that
      promotes mutual trust and effective communication. The primary aim of the study
      was to evaluate the impact of interprofessional learning on knowledge about
      diabetes. METHODS: The cross-sectional study included students of medicine,
      dentistry and nursing at the Faculty of Medicine Foca, Bosnia and Herzegovina.
      The students were randomly allocated into one of two groups. Group 1 attended an
      interprofessional course on diabetes while group 2 was divided into three
      subgroups and each of the subgroups attended an uniprofessional diabetes course.
      The measuring instrument used in the course in order to assess the participants'
      knowledge about diabetic care was a test containing multiple-choice questions
      about diabetes. The Interprofessional Questionnaire was used to explore the
      attitudes, views, values and beliefs of students regarding interprofessional
      education (IPE). RESULTS: No statistically significant difference in total score
      on the test was found between the groups at baseline, but at follow-up the
      difference was highly statistically significant (F=10.87; p=0.002). The students
      from Group 1 had better results (21.82 points), compared to Group 2 (18.77
      points). The statistically significant difference was observed in mean values (t=
      3.997; p=0.001), between Groups 1 and 2; the students from Group 1 obtained 20.42
      points, which is considered to indicate a respectively positive self-assessment
      of communication and teamwork skills. However, Group 2 indicated a negative self
      assessment of communication and teamwork skills. CONCLUSION: The findings suggest
      that IPE activities may provide health profession students with valuable
      collaborative learning opportunities.

PMID- 29338279
TI  - The chondrocoracoideus muscle: A rare anatomical variant of the pectoral area.
AB  - OBJECTIVE: The study adds important information regarding the descriptive anatomy
      of a very rarely reported unilateral chondrocoracoideus muscle (of Wood).
      Additionally it highlights the concomitant muscular and neural alterations. CASE
      REPORT: The current case presents the occurrence of a chondrocoracoideus muscle
      situated left-sided, as an extension of the abdominal portion of the pectoralis
      major muscle (PM). The chondrocoracoideus coexisted with a contralateral atypical
      PM, partially blended with the clavicular fibers of the deltoid muscle. There was
      an accessory head of the biceps brachii while the palmaris longus was absent on
      the right side of a 78-year-old Greek male cadaver. CONCLUSION: The above
      mentioned muscular abnormalities are shown as disturbances of embryological
      pectoral muscle development, and their documentation is essential in order to
      increase awareness among clinicians of their potential impact on the diagnosis
      and treatment of several pathologies.

PMID- 29338280
TI  - Variable skeletal anatomical features of acromegaly in the skull and
      craniocervical junction.
AB  - OBJECTIVE: This study adds important information regarding the morphological
      alterations caused by growth hormone hypersecretion in the skull and
      craniocervical junction (CCJ). A variably asymmetric skull due to acromegaly
      coexists with expansion of the paranasal sinuses and multiple Wormian bones. CASE
      REPORT: A pathologically asymmetric dry skull of a European male, aged 38 years
      at death, with cranial vault and skull base thickening is described. The
      extensive paranasal sinus pneumatization caused a generalized thinning of the
      bony walls. The sphenoid sinus expanded intraorbitally, leading to sella
      enlargement. The orbital asymmetry coexisted with platybasia and hypoplasia of
      the occipital condyles and the odontoid process. Facial skeleton elongation and
      mandibular overgrowth were combined with prognathism, malocclusion and overbite.
      CONCLUSION: Skull and CCJ alterations are of paramount importance when selecting
      the surgical approach, if surgery is indicated. Consecutively, detailed
      preoperative evaluation and planning is essential. During surgery, skilled and
      experienced neurosurgeons recognize anatomical landmarks, use neuronavigation and
      micro-instrumentation in order to remain on the midline avoiding any potential
      lethal vascular injury.

PMID- 29338281
TI  - Severe vertebral erosion by chronic contained rupture of an abdominal aortic
      aneurysm.
AB  - No abstract available.

PMID- 29338282
TI  - Spontaneous closure of a full thickness macular hole.
AB  - No abstract available.

PMID- 29338283
TI  - Intussuscepted Meckel's diverticulum within its own lumen.
AB  - No abstract available.

PMID- 29338284
TI  - Healing invisible wounds - have we done enough to help the victims of wartime
      rape?
AB  - No abstract available.

PMID- 29338285
TI  - Response to whether the definition of the term "children born of war" and
      vulnerabilities of children from recent conflict and post-conflict settings
      should be broadened.
AB  - No abstract available.

PMID- 29338286
TI  - Reflections on the definition and categorization of "Children Born of War".
AB  - No abstract available.

PMID- 29338288
TI  - Transcranial magnetic stimulation (TMS) safety: a practical guide for
      psychiatrists.
AB  - OBJECTIVES: Repetitive transcranial magnetic stimulation (rTMS) is increasingly
      being utilised as a treatment option for depression, and with this comes a need
      for a practical review of safety issues intended for clinicians. This article
      provides an overview of the current literature regarding safety issues with rTMS
      for depression, and provides recommendations for clinical practice. CONCLUSIONS:
      Overall, rTMS is a well-tolerated treatment with common side effects (such as
      headache or local pain at the site of stimulation) being mild. Severe adverse
      effects, such as seizures, hearing impairment or mania, are uncommon. Certain
      populations, including adolescents, pregnant women, older adults and those with
      metal/electronic implants, require special consideration when prescribing and
      monitoring treatment courses. With adequate assessment and monitoring processes,
      rTMS can be administered safely in a large proportion of depressed patients.

PMID- 29338289
TI  - A systematic review of risk factors for methamphetamine-associated psychosis.
AB  - OBJECTIVE: Chronic methamphetamine use is commonly associated with the
      development of psychotic symptoms. The predictors and correlates of
      methamphetamine-associated psychosis are poorly understood. We sought to
      systematically review factors associated with psychotic symptoms in adults using
      illicit amphetamine or methamphetamine. METHODS: A systematic literature search
      was performed on MEDLINE (OVID), PsycINFO and EMBASE databases from inception to
      8 December 2016. The search strategy combined three concept areas:
      methamphetamine or amphetamine, psychosis and risk factors. Included studies
      needed to compare adults using illicit methamphetamine or amphetamine, using a
      validated measure of psychosis, on a range of risk factors. Of 402 identified
      articles, we removed 45 duplicates, 320 articles based on abstract/title and 17
      ineligible full-text articles, leaving 20 included studies that were conducted in
      13 populations. Two co-authors independently extracted the following data from
      each study: country, setting and design; participant demographic and clinical
      details; sample size; measure/s used and measures of association between
      psychosis outcomes and risk factors. Individual study quality was assessed using
      a modified Newcastle-Ottawa Scale, and strength of evidence was assessed using
      GRADE criteria. RESULTS: Frequency of methamphetamine use and severity of
      methamphetamine dependence were consistently found to be associated with
      psychosis, and sociodemographic factors were not. There was inconsistent evidence
      available for all other risk factors. Individual study quality was low-moderate
      for the majority of studies. Heterogeneity in study outcomes precluded
      quantitative synthesis of outcomes across studies. CONCLUSION: The most
      consistent correlates of psychotic symptoms were increased frequency of
      methamphetamine use and dependence on methamphetamine. The findings of this
      review highlight the need for targeted assessment and treatment of
      methamphetamine use in individuals presenting with psychosis.

PMID- 29338290
TI  - Barking Our Way Into the Year of the Dog: Public Health Benefits and Challenges.

PMID- 29338291
TI  - Indications for Surgical Repair of Type 1 Laryngeal Cleft.
AB  - OBJECTIVES: Type 1 laryngeal cleft (T1LC) is a congenital deficiency in the
      posterior glottis, resulting in a communication between the hypopharynx and
      glottis. No consensus treatment paradigm exists for timing and criteria for
      patient selection for surgical repair. Our goal is to assess whether patient
      characteristics can help predict improvement after surgery. METHODS: After
      Institutional Review Board exemption, a retrospective chart review was performed
      for patients undergoing surgery to diagnose a T1LC. Charts were examined for age,
      presenting symptoms, comorbidities, pre/postoperative videoflouroscopic swallow
      study reports, and outcomes. RESULTS: Ninety-seven patients with clinical
      suspicion for T1LC underwent direct laryngoscopy and bronchoscopy, and 63 (64%)
      were diagnosed with a T1LC. Twenty-two patients (63%) undergoing surgery achieved
      clinical or radiographic improvement. There was no difference in average age,
      aspiration, or penetration between clinical improvement and no improvement
      groups. Of 13 patients with comorbidities that increase their risk of aspiration,
      12 were significantly improved. There were 5 complications, which were managed
      conservatively. CONCLUSIONS: Our experience supports the repair of T1LC repair at
      time of diagnostic laryngoscopy if satisfactory improvement is not noted with
      conservative treatment. This should be performed without segregation for age,
      comorbidities, or degree of dysphagia. Our technique is performed with minimal
      complications and achieves satisfactory results.

PMID- 29338293
TI  - Betrixaban: A New Oral Factor Xa Inhibitor for Extended Venous Thromboembolism
      Prophylaxis in High-Risk Hospitalized Patients.
AB  - OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and safety of
      the factor Xa (FXa) inhibitor betrixaban for extended-duration prophylaxis of
      acute medically ill patients with venous thromboembolism (VTE) risk factors. DATA
      SOURCES: A MEDLINE/PubMed (January 1990 to October 2017) search was conducted
      using the following keywords: betrixaban, PRT054021, FXa inhibitor, novel oral
      anticoagulant, NOAC, direct oral anticoagulant, DOAC, and target specific oral
      anticoagulant, TSOAC. References of identified articles were searched by hand for
      additional relevant citations. STUDY SELECTION AND DATA EXTRACTION: We included
      English-language articles evaluating betrixaban pharmacology, pharmacokinetics,
      efficacy, or safety in human subjects for VTE prophylaxis. DATA SYNTHESIS:
      Betrixaban is a FXa inhibitor that decreases prothrombinase activity and thrombin
      generation. Betrixaban efficacy and safety has been compared with that of
      enoxaparin for prophylaxis of VTE in acutely ill medical patients. In the APEX
      trial and substudies, extended-duration betrixaban was superior in efficacy to
      standard-duration enoxaparin in patients at high risk for VTE, including those
      with elevated D-dimer levels (>=2* upper limit of normal) and of older age (>=75
      years). Betrixaban is noninferior to enoxaparin in rates of major bleeding, but
      the former is associated with more clinically relevant nonmajor bleeding events.
      CONCLUSION: Betrixaban is the first oral agent approved for extended-duration VTE
      prophylaxis in acutely ill hospitalized patients. Extended-duration
      thromboprophylaxis with betrixaban reduces the risk of VTE compared with standard
      duration thromboprophylaxis with enoxaparin but is associated with increased risk
      of bleeding.

PMID- 29338292
TI  - Temporalis Fascia Transplantation for Sulcus Vocalis and Vocal Fold Scar: Long
      Term Outcomes.
AB  - OBJECTIVE: Sulcus vocalis and vocal fold scar involve derangement of the
      superficial lamina propria of the vocal fold, which results in significant
      dysphonia. Many options exist for treatment, most of which have unsatisfactory
      and unpredictable outcomes. Autologous transplantation of temporalis fascia into
      the vocal fold (ATFV) has the potential to be a better treatment option, but long
      term outcomes have not been well studied. METHODS: Retrospective chart review and
      patient survey. Twenty-one patients diagnosed with vocal fold scar or sulcus
      vocalis and treated with ATFV with at least 1-year follow-up were included. Voice
      Handicap Index 10 (VHI-10) questionnaires were collected preoperatively and 6
      months postoperatively. Patients were reached at the time of the study to
      complete another VHI-10 and a Likert scale survey. RESULTS: The mean decrease in
      VHI-10 scores between preoperation and 6 months postoperation was 8.35 ( P <
      .001). From preoperation to the time of the study (average 44 months; range, 12
      72 months), the VHI decreased 13.53 ( P < .001). Eighty-eight percent of patients
      reported they would recommend this surgery to others with the same diagnosis.
      Only 1 minor self-limited complication occurred. CONCLUSION: Autologous
      transplantation of temporalis fascia into the vocal fold for the treatment of
      vocal fold scar and sulcus vocalis is a safe surgery with good long-term outcomes
      and high patient satisfaction.

PMID- 29338294
TI  - The importance of clinical observation: A case of subtle tardive dyskinesia with
      paliperidone palmitate.

PMID- 29338295
TI  - A Scoping Review of Inclusive Out-of-School Time Physical Activity Programs for
      Children and Youth With Physical Disabilities.
AB  - The objective of this study was to comprehensively evaluate inclusive out-of
      school time physical activity programs for children/youth with physical
      disabilities. A search of the published literature was conducted and augmented by
      international expertise. A quality appraisal was conducted; only studies with
      quality ratings >=60% informed our best practice recommendations. Seventeen
      studies were included using qualitative (n = 9), quantitative (n = 5), or mixed
      (n = 3) designs. Programs had a diversity of age groups, group sizes, and
      durations. Most programs were recreational level, involving both genders.
      Rehabilitation staff were the most common leaders. Outcomes focused on social
      skills/relationships, physical skill development, and psychological well-being,
      with overall positive effects shown in these areas. The best practice
      recommendations are consistent with an abilities-based approach emphasizing
      common group goals and interests; cooperative activities; mastery-oriented,
      individualized instruction; and developmentally appropriate, challenging
      activities. Results indicate that inclusive out-of-school time physical activity
      programs are important for positive psychosocial and physical skill development
      of children/youth with physical disabilities.

PMID- 29338296
TI  - Tips and tricks in axillary cannulation.

PMID- 29338297
TI  - Unusual case of left atrial myxoma with gastroesophageal junction adenocarcinoma.
AB  - Cardiac myxomas are rare tumors. Esophageal adenocarcinomas are common tumors of
      the gastrointestinal tract. Simultaneous occurrence of these tumors has not been
      reported. A 52-year-old gentleman presented to our hospital with dysphagia and
      was diagnosed with esophageal adenocarcinoma. Routine echocardiography discovered
      a cardiac tumor in the left atrium. The cardiac tumor was surgically removed and
      biopsy confirmed a myxoma. We removed the cardiac tumor as the first step and
      then initiated neoadjuvant chemotherapy. It is ideal to constitute a
      multidisciplinary team to decide on the course of treatment in such cases.

PMID- 29338298
TI  - Coronary and arch hybrid surgery in a patient with infrarenal aortic occlusion.
AB  - A 65-year-old gentleman with claudication underwent contrast-enhanced computed
      tomography. The scan showed occlusion of the infrarenal abdominal aorta and a 6.0
      * 3.7 cm saccular zone-3 arch aneurysm. The left ventricular ejection fraction
      was 35% and a coronary angiogram revealed triple-vessel disease. In view of the
      patient's high risk with EuroSCORE II 20.34%, coronary artery surgery was
      combined with hybrid type I arch aneurysm repair. An endovascular stent was
      delivered in an antegrade manner. Open heart surgery and a hybrid type I arch
      intervention can be performed simultaneously through a midline sternotomy
      approach.

PMID- 29338299
TI  - Mitral valve replacement via a left thoracotomy in dextrocardia and situs
      solitus.
AB  - Dextrocardia with situs solitus and severe mitral regurgitation is a rare
      clinical presentation which posse a surgical challenge and requires specific
      preoperative planning. A 54-year-old women with this anatomy, multiple thoracic
      procedures, and severe mitral valve regurgitation underwent successful mitral
      valve replacement with a 27-mm mechanical prosthesis through a left thoracotomy
      under ventricular fibrillation, on the basis of computed tomography findings. We
      emphasize the importance of preoperative planning and a surgical approach through
      a left thoracotomy and under ventricular fibrillation.

PMID- 29338300
TI  - Penetrating injury of the ascending aorta complicating a sternal biopsy.
AB  - Bone marrow aspiration and trephine biopsy are considered safe procedures. Some
      serious but rare adverse events directly attributable to these procedures have
      been related in a few reports in the literature. We report a rare case of
      ascending aortic injury following a sternal trephine biopsy.

PMID- 29338301
TI  - Coronary artery perforation complicating percutaneous coronary intervention.
AB  - Background Coronary artery perforation is a rare but serious complication of
      percutaneous coronary interventions. We aimed to evaluate the management of
      coronary artery perforation in Sulaimaniyah, Iraq. Methods A retrospective review
      of our medical records from 2009 to 2016 identified 24 patients (15 males, 9
      females) with coronary artery perforation. Mean age was 60 +/- 9.2 years (range
      40-74 years). Standard diagnostic angiography or percutaneous interventions were
      performed. Coronary artery perforation was diagnosed by worsening of symptoms,
      hypotension, or angiographic evidence of type I (extraluminal crater), II
      (myocardial or pericardial blushing), or III (contrast streaming or cavity
      spilling) perforation. Stenosis was graded as >85%, 60%-85%, or < 60%. Once
      coronary artery perforation was diagnosed, heparin was reversed, antiplatelets
      were stopped, and pericardial effusions were aspirated. Type II and III coronary
      artery perforations were sealed using covered stents or repeated brief balloon
      inflations. Results The most frequently injured artery was the left anterior
      descending ( n = 14, 58.3%). Type II and III coronary artery perforations
      constituted the majority ( n = 18, 75%). Thirteen (54.2%) patients had severe
      coronary stenosis. Perforations were caused by stents ( n = 10), angioplasty
      wires ( n = 8), and balloons ( n = 6). Fifteen perforations were sealed with
      covered stents, 2 by balloon inflations, and 7 resolved spontaneously.
      Pericardial effusion was drained in 13 (54.2%) patients. No patient required
      surgery, and none died. Conclusion The low rate and early management of coronary
      artery perforations, mainly by covered stents, were the hallmarks of this study.

PMID- 29338303
TI  - Evaluation of Preprocedural Laboratory Parameters as Predictors of Drug-Eluting
      Stent Restenosis in Coronary Chronic Total Occlusion Lesions.
AB  - This retrospective, single-center study assessed the prognostic value of several
      emerging inflammatory markers as predictors of in-stent restenosis (ISR) after
      drug-eluting stent implantation for coronary chronic total occlusion (CTO)
      lesions. Consecutive patients (n = 416) who underwent successful percutaneous
      coronary intervention (PCI) for documented CTO lesions and with follow-up
      angiography were enrolled. Preprocedural high-sensitivity C-reactive protein
      (hsCRP), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio
      (PLR), and red cell distribution width (RDW) were analyzed. At mean follow-up of
      14.4 +/- 3.3 months, ISR occurred in 72 patients. Compared with the non-ISR
      group, preprocedural hsCRP level, PLR, NLR, and RDW were significantly higher in
      the ISR group. The ISR group also had significantly greater proportions of
      patients with diabetes and smoking history, lower estimated glomerular filtration
      rate, higher low-density lipoprotein cholesterol (LDL-C) level and neutrophil
      count, longer stent length, and higher rate of severe dissection. In multivariate
      analysis, NLR (odds ratio [OR]: 3.110; 95% confidence interval [CI], 2.102-4.063;
      P < .001) and PLR (OR: 1.029; 95% CI, 1.016-1.143; P < .001) were independent
      predictors of ISR, along with LDL-C level and stent length. In conclusion, higher
      preprocedural NLR and PLR levels were independent risk factors for the
      development of ISR in patients who underwent PCI for CTO lesions.

PMID- 29338302
TI  - Neurotransmitter Pathway Genes in Cognitive Decline During Aging: Evidence for
      GNG4 and KCNQ2 Genes.
AB  - BACKGROUND/RATIONALE: Experimental studies support the role of neurotransmitter
      genes in dementia risk, but human studies utilizing single variants in candidate
      genes have had limited success. METHODS: We used the gene-based testing program
      Versatile Gene-based Association Study to assess whether aggregate variation
      across 6 neurotransmitter pathways influences risk of cognitive decline in 8159
      cognitively normal elderly (>=65 years old) adults from 3 community-based
      cohorts. RESULTS: Common genetic variation in GNG4 and KCNQ2 was associated with
      cognitive decline. In human brain tissue data sets, both GNG4 and KCNQ2 show
      higher expression in hippocampus relative to other brain regions; GNG4 expression
      decreases with advancing age. Both GNG4 and KCNQ2 show highest expression in
      fetal astrocytes. CONCLUSION: Genetic variation analyses and gene expression data
      suggest that GNG4 and KCNQ2 may be associated with cognitive decline in normal
      aging. Gene-based testing of neurotransmitter pathways may confirm and reveal
      novel risk genes in future studies of healthy cognitive aging.

PMID- 29338304
TI  - Investigation of the use of external aluminium targets for portal imaging in a
      medical accelerator using Geant4 Monte Carlo simulation.
AB  - OBJECTIVE: To install a low-Z target on the wedge tray mount of a medical linear
      accelerator to create a new image beam and to confirm image contrast enhancement.
      METHODS: Experimental low-energy photon beams were produced with the linac
      running in the 6 MeV electron mode and with a low-Z target installed on the wedge
      tray mount [denoted 6 MeV (low-Z target)]. Geant4 Monte Carlo simulation was
      performed to analyse the energy spectrum and image contrast of a 6 MeV (low-Z
      target) beam. This study modelled the 6 MeV (low-Z target) beam and the 6 MV
      (megavoltage) radiotherapy photon beam and verified model validity by
      measurement. In addition, a contrast phantom was modelled to quantitatively
      compare the image contrasts of the 6 MeV (low-Z target) beam and the 6 MV
      radiotherapy photon beam. A low-Z target was fabricated to generate low-energy
      photons (25-150 keV) from incident electrons, and a portal image of the Alderson
      RANDO phantom was acquired using a clinical linear accelerator for qualitative
      analysis. RESULTS: The measured and calculated percentage depth dose of the 6 MV
      photon and 6 MeV (Al) beams were consistent within 1.5 and 1.6%, respectively,
      and calculated lateral profiles of the 6 MV photon beam and the 6 MeV (Al) beam
      were consistent with the measured results within 1.5 and 1.9%, respectively.
      Although low-energy photons (25-150 keV) of the 6 MV photon beam were only 0.3%,
      the Be, C, and Al low-Z targets, but not the Ti target, generated 34.4 to 38.5%
      low-energy photons. In 5 to 20 cm water phantoms, contrast of the 6 MeV (Al) beam
      was approximately 1.16 times greater than that of the 6 MV beam. The contrasts of
      6 MeV (Al) and 6 MV photon beams in the 20 cm water phantom were ~34% lower than
      those in the 5 cm water phantom. 6 MeV (Al)/CR (computed radiography) images of
      the human body phantom were more vivid and detailed than 6 MV/EPID (electronic
      portal imaging device) and 6 MeV (Al)/EPID images. CONCLUSION: The experimental
      beam with a low-Z target, which was simply installed on the wedge tray mount of
      the radiotherapy linear accelerator, generated significantly more low-energy
      photons than the 6 MV radiotherapy photon beam, and provided better quality
      portal images. Advances in knowledge: This study shows that, unlike the existing
      low-Z beam studies, a low-Z target can be installed outside the head of a linear
      accelerator to improve portal image quality.

PMID- 29338306
TI  - Biomarkers for assessing the effectiveness of immunotherapy in breast cancer.

PMID- 29338305
TI  - Safety and feasibility of prostate stereotactic ablative radiotherapy using
      multimodality imaging and flattening filter free.
AB  - OBJECTIVE: To investigate feasibility and safety of stereotactic ablative
      radiotherapy in the management of prostate cancer while employing MR/CT fusion
      for delineation, fiducial marker seeds for positioning and Varian RapidArc with
      flattening filter free (FFF) delivery. METHODS: 41 patients were treated for low
      intermediate risk prostate cancer with initial prostate-specific antigen of <=20
      ng ml-1, Gleason score 6-7. Patients had MR/CT fusion for delineation of prostate
      +/-seminal vesicles. CT/MR fusion images were used for delineation and planned
      using flattening filter free modality. Verification on treatment was cone beam CT
      imaging with fiducial markers for matching. Patients had Radiation Therapy
      Oncology Group scoring for genitourinary and gastointestinal symptoms at
      baseline, week 4, 10 and 18. RESULTS: Clinically acceptable plans were achieved
      for all patients, all plans achieved the objective clinical target volume D99% >=
      95%, and for planning target volume D95% >= 95%. Rectum dose constraints were met
      for 95.1% for V18 Gy <= 35%, 80% V28 Gy <= 10%. A total of 32 (78.0%) plans
      achieved all rectum dose constraints. Grade 1 acute genitourinary symptoms were
      53.7% of patients at baseline, 90.2% [95% CI (76.8-97.3%)] (p = 0.0005) at
      treatment 5, falling to 78.0% (62.4-89.4%) at week 4, and 75.0% (58.8-87.3%) by
      week 10 and 52.5% (36.1-68.5%) (p = 1.00) at week 18. Acute gastrointestinal
      symptoms were 5% at baseline, 46.3% [95% CI (30.7-62.6%)] at treatment 5, week 4
      43.9% [95% CI (28.5-60.3%)], week 10 25.0% (11.1-42.3%), and declined slightly by
      week 18 [-20.095% CI (12.7-41.2)] p = 0.039. Overall 75.6% (31/41) of patients
      experienced Grade 1-2 toxicity during or after treatment. CONCLUSION: This
      planning and delivery technique is feasible, safe and efficient. A homogeneous
      dose can be delivered to prostate with confidence, whilst limiting high dose to
      nearby structures. The use of this technology can be applied safely within
      further randomized study protocols. Advances in knowledge: Multimodality imaging
      for delineation and linac-based image-guided RT with FFF for the treatment of
      prostate stereotactic ablative radiotherapy.

PMID- 29338307
TI  - The impact of prehabilitation on post-surgical complications in patients
      undergoing non-urgent cardiovascular surgical intervention: Systematic review and
      meta-analysis.
AB  - Introduction Cardiac surgery is an aggressive procedure, inducing a great level
      of stress and disturbance to the homeostasis of the organism and underlying
      several postoperative complications. Surgical prehabilitation comprises pre
      operative physical conditioning designed to improve the physiological and
      functional capacities of the individual, prepare the organism for surgical stress
      and reduce the risk of postoperative morbidity. Aim This systematic review and
      meta-analysis is aimed at evaluating the ability of prehabilitation to prevent
      post-surgical complications in cardiac patients. Methods We selected studies
      conducted among patients who were waiting for non-urgent cardiac surgical
      procedures, where a comparison between prehabilitation and standard treatment was
      made. A total of 3650 possible studies were researched, of which eight were
      selected for inclusion. Results A reduction in the number of complications in the
      groups submitted to prehabilitation (odds ratio = 0.41; 95% confidence interval
      (CI): 0.28-0.62; p < 0.001; I2 = 0%) was observed, as well as a significant
      increase in maximal inspiratory pressure (standard mean difference (SMD) = 0.66;
      95% CI: 0.35-0.96; p < 0.001; I2 = 58%), a non-significant decrease in the length
      of stay (SMD = -0.56; 95% CI: -1.13, 0.01; p = 0.05; I2 = 93%), a non-significant
      increase in the distance walked by the intervention group in the six-minute walk
      test (SMD = 0.89; 95% CI -0.06, 1.84; p = 0.07) and a lack of effect on
      mechanical ventilation time (SMD = -0.03; 95% CI: -0.22, 0.16; p = 0.75; I2 =
      0%). Conclusion Prehabilitation reduces the number of post-surgical complications
      and increases maximal inspiratory pressure; a reduction in the length of stay and
      an improvement of functional capacities are also probable.

PMID- 29338308
TI  - Calcium supplement is a major concern for patients with cardiovascular diseases.

PMID- 29338311
TI  - Sinophobia. Anxiety, violence, and the making of Mongolian identity, by Franck
      Bille.

PMID- 29338309
TI  - Oral microbiota reduce wound healing capacity of epithelial monolayers,
      irrespective of the presence of 5-fluorouracil.
AB  - Oral mucositis is still one of the most painful side effects of chemotherapeutic
      treatment and a mounting body of evidence suggests a key role for the oral
      microbiome in mucositis development. However, the underlying mechanisms remain
      elusive. In this work, we have investigated the interactions between the host,
      the microbiome, and chemotherapeutic treatments in more detail. The effect of 5
      fluorouracil, commonly inducing mucositis, was assessed on a co-culture model
      that consists of an epithelial cell layer and a biofilm derived from oral
      microbiota from different types of samples (saliva, buccal swabs and tongue
      swabs) and donors (healthy individuals and patients suffering from mucositis).
      After 24 h co-incubation, all oral microbial samples were found to reduce wound
      healing capacity with 26 +/- 15% as compared with untreated condition. Compared
      with saliva and tongue samples, buccal samples were characterized by lower
      bacterial cell counts and hence higher wound healing capacity. For samples from
      healthy individuals, an inverse correlation was observed between bacterial cell
      counts and wound healing capacity, whereas for patients suffering from mucositis
      no correlation was observed. Moreover, patient-derived samples had a less diverse
      microbial community and higher abundances of pathogenic genera. No major impact
      of 5-fluorouracil on wound healing capacity or the composition of the microbiome
      was seen at physiologically relevant concentrations in the mouth. In conclusion,
      bacterial cell count is inversely correlated with wound healing capacity, which
      emphasizes the importance of oral hygiene during oral wound healing in healthy
      individuals. However, future research on extra measures besides oral hygiene is
      needed to assure a good wound healing during mucositis, as for patients the
      bacterial composition seems also crucial. The direct effect of 5-fluorouracil on
      both the microbiome and wound healing is minimal, pointing to the importance of
      the host and its immune system in chemotherapy-induced microbial shifts. Impact
      statement Chemotherapy-induced oral mucositis has a major impact on the quality
      of life of patients. The additional costs and treatment time associated with this
      pathology are significant. Although the pathology of the disease is well
      understood, the role and importance of oral microbiota currently are less clear.
      In this study, we focused on the effect of oral microbiota on wound healing, the
      final phase of oral mucositis, during 5-FU exposure. We show that the bacterial
      load and composition have a major impact on the healing process in contrast to 5
      FU which only marginally slows down healing. This emphasizes the importance of
      good oral health care during oral mucositis to minimize bacterial load around the
      oral lesions. However, since we show that also the composition of the oral
      microbiome plays a role in wound recovery, the identification of specific
      pathogenic species or their metabolites might be worthwhile to allow proper
      treatment.

PMID- 29338310
TI  - Therapy-Induced Plasticity in Chronic Aphasia Is Associated with Behavioral
      Improvement and Time Since Stroke.
AB  - Cortical reorganization after stroke is thought to underlie functional
      improvement. Patterns of reorganization may differ depending on the amount of
      time since the stroke or the degree of improvement. We investigated these issues
      in a study of brain connectivity changes with aphasia therapy. Twelve individuals
      with chronic aphasia participated in a 6-week trial of imitation-based speech
      therapy. We assessed improvement on a repetition test and analyzed effective
      connectivity during functional magnetic resonance imaging of a speech observation
      task before and after therapy. Using structural equation modeling, patient
      networks were compared with a model derived from healthy controls performing the
      same task. Independent of the amount of time since the stroke, patients
      demonstrating behavioral improvement had networks that reorganized to be more
      similar to controls in two functional pathways in the left hemisphere.
      Independent of behavioral improvement, patients with remote infarcts (2-7 years
      poststroke; n = 5) also reorganized to more closely resemble controls in one of
      these pathways. Patients with far removed injury (>10 years poststroke; n = 3)
      did not show behavioral improvement and, despite similarities to the normative
      model and overall network heterogeneity, reorganized to be less similar to
      controls following therapy in a distinct right-lateralized pathway. Behavioral
      improvement following aphasia therapy was associated with connectivity more
      closely approximating that of healthy controls. Individuals who had a stroke more
      than a decade before testing also showed plasticity, with a few pathways becoming
      less like controls, possibly representing compensation. Better understanding of
      these mechanisms may help direct targeted brain stimulation.

PMID- 29338312
TI  - Assessment of Parental Acceptability and Preference for Behavioral Interventions
      for Feeding Problems.
AB  - The present study evaluates the treatment acceptability and preference for
      behavioral interventions for feeding problems with parents of children with
      Autism Spectrum Disorder and other developmental disabilities. The impact of
      behavioral severity on acceptability and preference was also evaluated by
      comparing results of parents who responded with respect to a vignette of a child
      with food refusal with those who responded to a vignette of a child with food
      selectivity. Overall, parents rated differential reinforcement of alternative
      behavior as the most preferred and most acceptable strategy across both food
      selectivity and food refusal groups. Escape extinction was the least acceptable
      and least preferred across both groups, and the severity of the behavior had no
      impact on acceptability or preference scores. Implications for future research on
      the social validity of feeding interventions are provided.

PMID- 29338313
TI  - Rapport Building and Instructional Fading Prior to Discrete Trial Instruction:
      Moving From Child-Led Play to Intensive Teaching.
AB  - Discrete trial instruction (DTI) is effective for teaching skills to children
      with autism spectrum disorder (ASD). Although effective, instructional settings
      can become aversive resulting in avoidant and escape-related behaviors. Given the
      significant social impairments associated with ASD, interventions that promote
      social approach and reduce avoidance are warranted. Rapport building or "pairing"
      the therapist and teaching setting with highly preferred activities prior to
      instruction can reduce problematic behaviors during subsequent instruction.
      However, the path from child-led play to DTI is not well established.
      Instructional fading may assist in bridging this gap. Four participants with ASD
      who were beginning an intensive behavioral intervention program were included in
      the current study. Participants progressed through nine stages of pairing and
      instructional fading with minimal problem behavior and high percentages of in
      seat and close proximity to the therapist. Guidelines for incorporating rapport
      building strategies prior to intensive teaching with children with ASD are
      proposed.

PMID- 29338314
TI  - Inflammatory Cytokines in the Papillary Tips and Urine of Nephrolithiasis
      Patients.
AB  - INTRODUCTION: Intrarenal inflammation has been implicated in the pathogenesis of
      nephrolithiasis, with prior work showing increased urine levels of IL-6, IL-8,
      and CCL-2 in stone patients. However, no studies have assessed for inflammation
      in the renal papillae. We sought to characterize novel papillary tip and urinary
      biomarkers in stone patients. MATERIALS AND METHODS: Ninety-two patients with
      nephrolithiasis undergoing percutaneous nephrolithotomy were enrolled. Papillary
      tip biopsies, kidney urine, and bladder urine were collected, as well as voided
      urine from eight healthy volunteers. Quantitative polymerase chain reaction was
      performed to measure inflammatory gene expression. RESULTS: Initial 84-gene
      polymerase chain reaction array revealed significant elevation of several
      cytokines in stone patients vs controls (fold change 2.3-694). Twenty-four genes
      were selected for final analysis. In 41 pairs of urine samples, levels of CCL5,
      CD40, FasL, RIPK2, SELE, TLR3, and IL-15 were significantly elevated in kidney vs
      bladder urine (p0.0001-0.04). In 23 triplets of samples, expression of these
      cytokines plus CCL2, CCL7, CCR2, CSF1, CXCL9, and CXCL10, was significantly
      greater in papillary tips vs urine samples (p0.001-0.05). Cytokine elevation was
      independent of maximum postoperative heart rate, respiratory rate, temperature,
      leukocyte count, urinary tract infection in the past year, presence or absence of
      antibiotics at the time of surgery, and stone composition (all p > 0.05).
      CONCLUSION: Expression of CCL-2, CCL-5, CCL-7, CCR-2, CD40, CSF1, CXCL-9, CXCL
      10, Fas-L, RIPK2, SELE, and TLR-3 is markedly elevated in the papillary tips,
      kidney urine, and bladder urine of nephrolithiasis patients. Cytokine elevation
      was independent of signs of systemic inflammation. These findings further support
      the role of inflammation in nephrolithiasis and imply that the inflammatory
      process likely begins at the renal papillae. These may represent novel biomarkers
      of stone disease, which may be useful in basic nephrolithiasis research, disease
      diagnosis, and prognosis.

PMID- 29338316
TI  - Retroareolar masses and intraductal abnormalities detected on screening
      ultrasound: can biopsy be avoided?
AB  - : To investigate the malignancy rate of retroareolar masses and intraductal
      abnormalities discovered in asymptomatic females during screening whole breast
      ultrasound (US-S) and determine if biopsy can be avoided. METHODS:: This is a
      HIPAA compliant retrospective study. Our radiology electronic medical records
      were searched for the phrases "retroareolar mass" or "intraductal mass" combined
      with "screening whole breast ultrasound" performed between 10/1/2009 and
      5/30/2015. Inclusion criteria included retroareolar masses in asymptomatic
      females with normal mammography, mammographically dense breast tissue and imaging
      or biopsy follow-up. RESULTS:: 1136 charts were reviewed. 87 BI-RADS 3 and 4
      retroareolar findings were included in final analysis. The average lesion size
      was 9.5 mm (range 4-28 mm). 47/87 lesions were classified as BI-RADS 3 and 40/87
      BI-RADS 4. Of the 47 BI-RADS 3 lesions, 36 were stable on follow-up; 6 benign
      lesions were biopsied at patients' request; and 5 biopsied due to suspicious
      interval change on follow-up imaging, including 4 benign lesions and a 5 mm Grade
      2 ductal carcinoma in situ . 3/40 BI-RADS 4 lesions were not biopsied and stable
      at follow-up; 37/40 lesions underwent benign biopsy. The malignancy rate of BI
      RADS 3 and 4 lesions was 2.1% [CI (0.4-11.1)] and 0% [CI (0.0-8.8)],
      respectively. The overall combined malignancy rate was 1/87 [1.1%, CI (0.2-6.2)].
      CONCLUSION:: The malignancy rate for BI-RADS 3 and 4 retroareolar masses and
      intraductal abnormalities detected on US-S is low (<2%). ADVANCES IN KNOWLEDGE::
      Careful imaging surveillance in lieu of biopsy of these lesions may be
      appropriate in asymptomatic females with negative mammography.

PMID- 29338317
TI  - Cosmos, gods and madmen: frameworks in the anthropologies of medicine, edited by
      Roland Littlewood and Rebecca Lynch.

PMID- 29338315
TI  - The chronic ischaemic cardiovascular disease ESC Pilot Registry: Results of the
      six-month follow-up.
AB  - Aim Chronic ischaemic cardiovascular disease (CICD) remains a leading cause of
      morbidity and mortality worldwide. The CICD Pilot Registry enrolled 2420 patients
      across 10 European Society of Cardiology countries prospectively to describe
      characteristics, management strategies and clinical outcomes in this setting. We
      report here the six-month outcomes. Methods and results From the overall
      population, 2203 patients were analysed at six months. Fifty-eight patients
      (2.6%) died after inclusion; 522 patients (23.7%) experienced all-cause
      hospitalisation or death. The rate of prescription of angiotensin-converting
      enzyme inhibitors, beta-blockers and aspirin was mildly decreased at six months
      (all P < 0.02). Patients who experienced all-cause hospitalisation or death were
      older, more often had a history of non-ST-segment elevation myocardial
      infarction, of chronic kidney disease, peripheral revascularisation and/or
      chronic obstructive pulmonary disease than those without events. Independent
      predictors of all-cause mortality/hospitalisation were age (hazard ratio (HR)
      1.17, 95% confidence interval (CI) 1.07-1.27) per 10 years, and a history of
      previous peripheral revascularisation (HR 1.45, 95% CI 1.03-2.03), chronic kidney
      disease (HR 1.31, 95% CI 1.0-1.68) or chronic obstructive pulmonary disease (HR
      1.42, 95% CI 1.06-1.91, all P < 0.05). We observed a higher rate of events in
      eastern, western and northern countries compared to southern countries and in
      cohort 1. Conclusion In this contemporary European registry of CICD patients, the
      rate of severe clinical outcomes at six months was high and was influenced by
      age, heart rate and comorbidities. The medical management of this condition
      remains suboptimal, emphasising the need for larger registries with long-term
      follow-up. Ad-hoc programmes aimed at implementing guidelines adherence and
      follow-up procedures are necessary, in order to improve quality of care and
      patient outcomes.

PMID- 29338318
TI  - Perceptions of patient-provider communication and receipt of mental health
      treatment among older adults with depressive symptoms.
AB  - OBJECTIVES: This study aimed to: (1) determine if and how perceptions towards
      healthcare providers differ between older adults with and without clinically
      signifcant depressive symptoms (CSDS), and (2) assess whether perceptions towards
      providers are associated with receipt of mental health treatment among older
      adults with CSDS. METHODS: Data from the 2013 and 2014 Medical Expenditure Panel
      Survey were used to examine CSDS prevalence, receipt of mental health treatment,
      and perceptions of provider communication among community-dwelling adults >= age
      65 (N = 6,936) using four of the 'How Well Doctors Communicate' composite items
      from the Consumer Assessment of Healthcare Providers and Systems(CAHPS).
      Multivariate logistic regression was used. RESULTS: CSDS are associated with
      greater odds of having 'poor' perceptions of provider communication on all four
      CAHPS communication measures. Perceptions of provider communication are similar
      among older adults with CSDS who received and did not receive mental health
      treatment, except on an item measuring a provider's ability to explain
      information in ways patients understand. CONCLUSION: Older adults with CSDS have
      more negative perceptions of the quality of their communication with healthcare
      providers than their peers. Healthcare systems should consider how to accommodate
      these patients' unique needs and communication preferences to ensure receipt of
      quality care.

PMID- 29338320
TI  - Effect of a group medical clinic for veterans with diabetes on body mass index.
AB  - Objective To assess the impact of a group medical clinic designed for patient
      with type 2 diabetes mellitus and hypertension on body mass index. Methods Using
      data from a randomized trial of 239 veterans with type 2 diabetes mellitus, we
      performed a secondary analysis using analysis of covariance mixed models to
      explore the effect of a 12-month group medical clinic intervention on change in
      body mass index vs. usual care. In an exploratory subgroup analysis, we compared
      change in body mass index between treatment arms stratified by whether patients
      had >0.5% reduction in hemoglobin A1c at 12 months. Results Baseline body mass
      index was 33.5 kg/m2. At 12 months, there was no significant difference in change
      in body mass index between treatment arms (estimate=-0.02, 95% CI -0.51 to 5.05;
      P = 0.94); body mass index increased by approximately 0.20 points in both groups.
      There was also no significant difference in change in body mass index between
      treatment arms by whether or not patients had >0.5% reduction in hemoglobin A1c
      (estimate=-0.14, 95% CI -1.21 to -0.92; P = 0.79). Discussion Improved glycemic
      control was not associated with improved body mass index in the group medical
      clinic intervention. Given their positive effects on other outcomes, group
      medical clinics for patients with type 2 diabetes mellitus may be more beneficial
      if focus is shifted towards weight loss.

PMID- 29338319
TI  - Clinical evaluation of circulating miR-548a-3p and -20a expression in malignant
      pleural mesothelioma patients.
AB  - AIM: miRNAs may act as promising diagnostic and prognostic biomarkers of
      mesothelioma. This study integrates serum  miR-548a-3p and miR-20a expression
      based on in silico data analysis followed by clinical validation in malignant
      mesothelioma patients (malignant pleural mesothelioma [MPM]). PATIENTS & METHODS:
      Serum miR-548a-3p and  miR-20a level was assessed in the serum of patients with
      MPM, chronic asbestos exposure and healthy volunteers by quantitative real-time
      PCR. RESULTS: The expression of serum miR-548a-3p and  miR-20a was positive in
      91.6 and 96.7% MPM patients, respectively. Both miRNAs were able to segregate
      between cases and controls. The sensitivity of the combined chosen serum miRNAs
      reached 100% in the diagnosis of MPM. CONCLUSION: The current work revealed that
      sera miR-548a-3p and miR-20a may serve as promising novel diagnostic tools for
      MPM.

PMID- 29338321
TI  - Are wishes for death or suicidal ideation symptoms of depression in older adults?
AB  - OBJECTIVE: Clinicians may question whether thoughts of being better off dead are
      normal consequences of aging or symptoms of depression. We examine whether
      thoughts of suicide are as strongly linked to depression severity in older adults
      as they are in other age groups. METHODS: Cross-sectional cohort study.
      Participants included 509,945 outpatients >18 years old from four large
      integrated healthcare systems in the Mental Health Research Network who completed
      1.2 million Patient Health Questionnaires (PHQ) and had data to calculate
      Charlson Comorbidity Index scores from 2010 through 2012. The PHQ8 estimated
      depression severity, while suicidal ideation was measured using the 9th item of
      the PHQ. Data were abstracted from a Virtual Data Warehouse. RESULTS: In older
      adult patients, suicidal ideation was strongly associated with depression
      severity. Older adults who had at least moderately-severe depression (PHQ8 >=15)
      were 48 times more likely (95% CI: 42.8-53.8) to report suicidal ideation than
      those with minimal or mild symptoms of depression (PHQ8 <10) after adjustment for
      all other variables in the model, including medical comorbidity burden.
      CONCLUSIONS: Depression severity was by far the strongest predictor of suicidal
      ideation in older adult patients. Older patients with suicidal ideation should be
      screened for depression.

PMID- 29338322
TI  - Associations of mindfulness with depressive symptoms and well-being in older
      adults: the moderating role of neuroticism.
AB  - OBJECTIVE: To investigate whether observed interactions of mindfulness with the
      personality trait neuroticism extend to older adults and to aspects of
      psychological functioning other than depressive symptoms, and whether effects of
      mindfulness training in this population depend on levels of neuroticism. METHOD:
      We performed a secondary analysis of data from a randomized controlled trial of
      Mindfulness-Based Stress Reduction (MBSR) for community-dwelling older adults. We
      investigated whether neuroticism moderates associations of dispositional
      mindfulness with various aspects of psychological and physical functioning at
      baseline, as well as effects of MBSR on these outcomes. RESULTS: Significant two
      way interactions showed that greater mindfulness was associated with fewer
      depressive symptoms and less negative affect at baseline in individuals with
      average or higher levels of neuroticism. In contrast, mindfulness was associated
      with greater positive affect and vitality and fewer physical symptoms regardless
      of the level of neuroticism. There were no effects of MBSR on these outcomes at
      any level of neuroticism. CONCLUSION: Mindfulness may be more protective against
      psychological ill-being in older adults with higher levels of neuroticism, but
      conducive to positive psychological and physical well-being regardless of this
      personality trait. The potential moderating role of neuroticism should be further
      evaluated in studies of mindfulness-based interventions in older adults.

PMID- 29338323
TI  - Psychosocial interventions for people with dementia: a synthesis of systematic
      reviews.
AB  - OBJECTIVES: Over the last 10 years there has been a multitude of studies of
      psychosocial interventions for people with dementia. However, clinical services
      face a dilemma about which intervention should be introduced into clinical
      practice because of the inconsistency in some of the findings between different
      studies and the differences in the study qualities and trustworthiness of
      evidence. There was a need to provide a comprehensive summary of the best
      evidence to illustrate what works. METHODS: A review of the systematic reviews of
      psychosocial interventions in dementia published between January 2010 and
      February 2016 was conducted. RESULTS: Twenty-two reviews (8 physical, 7
      cognitive, 1 physical/cognitive and 6 other psychosocial interventions) with a
      total of 197 unique studies met the inclusion criteria. Both medium to longer
      term multi-component exercise of moderate to high intensity, and, group cognitive
      stimulation consistently show benefits. There is not sufficient evidence to
      determine whether psychological or social interventions might improve either mood
      or behaviour due to the heterogeneity of the studies and interventions included
      in the reviews. CONCLUSION: There is good evidence that multi-component exercise
      with sufficient intensity improves global physical and cognitive functions and
      activities of daily living skills. There is also good evidence that group-based
      cognitive stimulation improves cognitive functions, social interaction and
      quality of life. This synthesis also highlights the potential importance of group
      activities to improve social integration for people with dementia. Future
      research should investigate longer-term specific outcomes, consider the severity
      and types of dementia, and investigate mechanisms of change.

PMID- 29338324
TI  - Effect of Vertical or Beveled Chondral Defect Creation on Rim Deformation and
      Contact.
AB  - Objective To determine biomechanical effects of knee cartilage defect perimeter
      morphology based on cartilage strain and opposing subchondral bone contact.
      Design Articular cartilage defects were created in 5 bovine femoral condyles:
      group 1, 45 degrees  inner bevel with 8-mm rim; group 2, vertical with 8-mm rim;
      and group 3, 45 degrees  outer bevel with 8-mm base. Samples were placed into a
      custom-machined micro-computed tomography tube and subjected to 800 N of axial
      loading. DICOM data were used to calculate cartilage thickness 4 and 6 mm from
      the center, distance between tibial cartilage surface and femoral subchondral
      bone, and contact width between tibial cartilage and subchondral bone. Strain 4
      mm from the center and both absolute and change in distance (mm) to subchondral
      bone were compared between groups 1 and 2 using paired t tests. Strain at 6 mm
      and distance changed, loaded distance, and contact width (mm) were compared
      between groups using the Friedman test with post hoc analysis using Wilcoxon
      signed rank test. Results No significant differences in rim strain were noted
      between groups 1 and 2 at 4 mm ( P = 0.10) and between groups 1, 2, and 3 at 6 mm
      ( P = 0.247) from the defect center. The loaded distance was significantly
      different between groups 1 and 3 ( P = 0.013). No significant change in distance
      to the subchondral bone was found between groups ( P = 0.156). The difference in
      subchondral bone contact area approached but did not reach significance ( P =
      0.074). Conclusion When debriding focal articular cartilage defects,
      establishment of an inner bevel decreases tissue deformation and contact with
      opposing subchondral bone.

PMID- 29338325
TI  - Comparative Evaluations of Randomly Selected Four Point-of-Care Glucometer
      Devices in Addis Ababa, Ethiopia.
AB  - BACKGROUND: Point-of-care glucometer (PoCG) devices play a significant role in
      self-monitoring of the blood sugar level, particularly in the follow-up of high
      blood sugar therapeutic response. The aim of this study was to evaluate blood
      glucose test results performed with four randomly selected glucometers on
      diabetes and control subjects versus standard wet chemistry (hexokinase) methods
      in Addis Ababa, Ethiopia. METHOD: A prospective cross-sectional study was
      conducted on randomly selected 200 study participants (100 participants with
      diabetes and 100 healthy controls). Four randomly selected PoCG devices (CareSens
      N, DIAVUE Prudential, On Call Extra, i-QARE DS-W) were evaluated against
      hexokinase method and ISO 15197:2003 and ISO 15197:2013 standards. RESULTS: The
      minimum and maximum blood sugar values were recorded by CareSens N (21 mg/dl) and
      hexokinase method (498.8 mg/dl), respectively. The mean sugar values of all PoCG
      devices except On Call Extra showed significant differences compared with the
      reference hexokinase method. Meanwhile, all four PoCG devices had strong positive
      relationship (>80%) with the reference method (hexokinase). On the other hand,
      none of the four PoCG devices fulfilled the minimum accuracy measurement set by
      ISO 15197:2003 and ISO 15197:2013 standards. In addition, the linear regression
      analysis revealed that all four selected PoCG overestimated the glucose
      concentrations. CONCLUSIONS: The overall evaluation of the selected four PoCG
      measurements were poorly correlated with standard reference method. Therefore,
      before introducing PoCG devices to the market, there should be a standardized
      evaluation platform for validation. Further similar large-scale studies on other
      PoCG devices also need to be undertaken.

PMID- 29338326
TI  - Diabetes mellitus and atrial remodelling in patients with paroxysmal atrial
      fibrillation: Role of electroanatomical mapping and catheter ablation.
AB  - Complex fractionated atrial electrograms (CFAEs) are related to atrial fibrosis,
      but their ablation has not yet shown superiority. The aim of the study was to
      compare, in terms of clinical outcome, two strategies of paroxysmal atrial
      fibrillation (AF) ablation in patients with type 1 diabetes mellitus (DM):
      pulmonary vein isolation (PVI) vs. PVI + CFAEs. Compared to an historical
      population of patient with paroxysmal AF and without DM, a higher percentage of
      patients with DM showed more than 25% of atrial area interested by CFAEs (study
      population, 58% vs historical group, 15%; p < 0.05). In PVI group, recurrences
      rate was similar in patients with HbA1c ? 7.5% vs HbA1c > 7.5% (30% vs 22%; p =
      not significant), but a greater AF burden was observed in patients with HbA1c >
      7.5% (6 +/- 2 vs 1 +/- 2; p < 0.05). In hazard ratios analysis PVI+CFAEs seems
      more effective than PVI alone in patients with HbA1c > 7.5% (hazard ratio, 1.28;
      p < 0.05), more than 25 years from DM diagnosis (hazard ratio, 1.25; p < 0.05)
      and more than five AF episodes/year (hazard ratio, 1.2; p < 0.05). Type 1 DM
      patients had complex atrial 'substrate', as documented by wider CFAEs areas.
      Despite this, 1-year follow-up recurrence rate was similar between two ablation
      approaches (PVI 27% vs. PVI+CFAEs 21%; p = not significant). In our study, only
      specific subgroups, like patients with disglycaemic state (HbA1c > 7.5%), long
      diabetes mellitus history and high AF burden, benefit from PVI+ CFAEs approach.

PMID- 29338327
TI  - Respiratory-gated PET/CT for pulmonary lesion characterisation-promises and
      problems.
AB  - 2-deoxy-2-(18Fluorine)-fluoro-D-glucose (FDG) PET/CT is an integral part of lung
      carcinoma staging and frequently used in the assessment of solitary pulmonary
      nodules. However, a limitation of conventional three-dimensional PET/CT when
      imaging the thorax is its susceptibility to motion artefact, which blurs the
      signal from the lesion resulting in inaccurate representation of size and
      metabolic activity. Respiratory gated (four-dimensional) PET/CT aims to negate
      the effects of motion artefact and provide a more accurate interpretation of
      pulmonary nodules and lymphadenopathy. There have been recent advances in
      technology and a shift from traditional hardware to more streamlined software
      methods for respiratory gating which should allow more widespread use of
      respiratory-gating in the future. The purpose of this article is to review the
      evidence surrounding four-dimensional PET/CT in pulmonary lesion
      characterisation.

PMID- 29338328
TI  - Avoidance, meaning and grief: psychosocial factors influencing engagement in HIV
      care.
AB  - Although the introduction of antiretroviral therapy has rendered HIV a chronic
      illness, inconsistent engagement in HIV care by key populations limits its public
      health impact. Poor engagement in care is especially prevalent among vulnerable
      populations with mental health and substance use disorders. Beyond structural and
      health system considerations, psychosocial factors may present challenges to
      sustained engagement. We conducted a qualitative study using in-depth interviews
      with 31 primarily African American, urban-based individuals, many with past or
      current drug use and mental disorders, living with HIV. Participants identified
      several psychosocial barriers that detract from their motivation to attend
      appointments and take medication. These included mental distress or detachment
      over a lack of purpose in life; denial about the need to be engaged in care;
      insufficient trust in the efficacy of care or the health system; deaths of loved
      ones leading to bereavement or loss of social support; and engagement in specific
      avoidance behaviors like drugs and alcohol. The study findings suggest that more
      comprehensive HIV care, which integrates mental health and substance abuse
      services in order to enhance meaning and address coping and grief, may be
      important. Considering these services in addition to improving the logistical
      components of care such as cues/reminders, accessibility, and patient-provider
      communication may improve intervention packages.

PMID- 29338329
TI  - Making a university community more dementia friendly through participation in an
      intergenerational choir.
AB  - A dementia friendly community is one that is informed about dementia, respectful
      and inclusive of people with dementia and their families, provides support,
      promotes empowerment, and fosters quality of life. This study presents data from
      four cohorts of undergraduate college students and people with dementia and their
      family members, using an intergenerational choir as the process through which to
      begin to create a dementia friendly community. This was accomplished by breaking
      down the stereotypes and misunderstandings that young adults have about people
      with dementia, thus allowing their commonalities and the strengths of the people
      living with dementia to become more visible. Data were gathered for each cohort
      of students through semi-structured open-ended questions on attitudes about
      dementia and experiences in the choir, collected at three points over 10 weeks of
      rehearsals. Data about their experiences in the choir were collected from each
      cohort of people with dementia and their family members through a focus group.
      Results across all four cohorts showed in the students: changed attitudes,
      increased understanding about dementia and the lived experience, reduced dementia
      stigma, and the development of meaningful social connections. People with
      dementia and their family members expressed feelings of being part of a
      community.

PMID- 29338330
TI  - Joint Influence of SNPs and DNA Methylation on Lipids in African Americans From
      Hypertensive Sibships.
AB  - INTRODUCTION: Plasma concentrations of lipids (i.e., total cholesterol, high
      density cholesterol, low-density cholesterol, and triglycerides) are amenable to
      therapeutic intervention and remain important factors for assessing risk of
      cardiovascular diseases. Some of the observed variability in serum lipid
      concentrations has been associated with genetic and epigenetic variants among
      cohorts with European ancestry (EA). Serum lipid levels have also been associated
      with genetic variants in multiethnic populations. METHODS: The purpose of this
      study was to determine whether single-nucleotide polymorphisms (SNPs) and DNA
      methylation (DNAm) differences contribute to lipid variation among African
      Americans ([AAs], N = 739) in the Genetic Epidemiology Network of Arteriopathy
      (GENOA) study. RESULTS: Previous meta-analyses identified 161 SNPs that are
      associated with lipid traits in populations of EA. We evaluated these SNPs and 66
      DNAm sites within the genes containing the SNPs in the GENOA cohort using linear
      mixed-effects modeling. We did not identify any significant associations of SNPs
      or DNAm with serum lipid levels. These results suggest that the SNPs identified
      as being significant for lipid levels through the EA genome-wide association
      studies may not be significant across AA populations. CONCLUSIONS: Reductions in
      morbidity and mortality due to variation in lipids among AAs may be achieved
      through a better understanding of the genetic and epigenetic factors associated
      with serum lipid levels for early and appropriate screening. Further large-scale
      studies specifically within AA and other non-EA populations are warranted.

PMID- 29338331
TI  - The impact of HIV diagnosis on length of hospital stay in New York City, NY, USA.
AB  - While hospitalizations among people living with human immunodeficiency virus
      (PLWH) have been elevated in the past compared to their uninfected counterparts,
      the introduction of antiretroviral therapy (ART) has resulted in great strides in
      controlling symptomatic infection. However, research largely overlooks important
      differences among HIV-infected individuals, primarily PLWH who are symptomatic
      versus those who are asymptomatic. We conducted a retrospective study assessing
      the length of hospital stay among 717,237 admissions from three hospitals in the
      New York City area. Using zero-truncated negative binomial regression we
      documented trends in length of hospital stay among individuals who are HIV
      positive (with symptoms versus those without symptoms) compared to HIV-negative
      patients over nine consecutive years, from 2006 to 2014. Approximately 0.85% of
      the admissions were infected with asymptomatic HIV (n = 6,131), while 1.43% of
      admissions were infected with symptomatic HIV (n = 10,271). The length of stay
      (LOS) among symptomatic HIV-infected admissions was 32.0% (95% CI: 29.7%-34.2%)
      longer than LOS in the general admissions. The mean LOS dropped about 1.5% (95%
      CI: 1.5%-1.6%) per year in the study sample. The LOS in inpatients with
      asymptomatic HIV had the same LOS as the general inpatient population. Our
      findings highlight the need for comprehensive strategies to reduce length of
      hospitalization among HIV-infected individuals.

PMID- 29338332
TI  - Venous Thromboembolism in Podiatric Foot and Ankle Surgery.
AB  - BACKGROUND: The extent to which podiatric surgeons follow venous thromboembolism
      guidelines is unknown. The aim of this study therefore, was 2-fold: (a) to
      determine the rate of venous thromboembolism following podiatric surgery and (b)
      to investigate the factors that influence the use of thromboprophylaxis. METHODS:
      Data from 4238 patients who underwent foot and ankle surgery over 2 years were
      analyzed. Venous thromboembolism within the first 30 days following surgery was
      recorded using the Australasian College of Podiatric Surgeons surgical audit
      tool. Logistic regression analyses were undertaken to determine the factors that
      influenced thromboprophylaxis. RESULTS: Of the 4238 patient records, 3677 records
      (87%) provided complete data (age range 2-94 years; mean +/- SD, 49.1 +/- 19.7
      years; 2693 females). A total of 7 venous thromboembolic events (0.2% rate) were
      reported. Operative duration and age (OR 12.63, 95% CI 9.47 to 16.84, P < 0.01),
      postoperative immobilization (OR 6.94, 95% CI 3.95 to 12.20, P < 0.01), and a
      prior history of VTE (OR 3.41, 95% CI 1.01 to 11.04, P = 0.04) were the strongest
      predictors of thromboprophylaxis. CONCLUSION: Podiatric foot and ankle surgery is
      associated with a low rate of venous thromboembolism. This may be due in part to
      the thromboprophylaxis regime implemented by podiatric surgeons, which closely
      aligns with current evidence-based guidelines. LEVELS OF EVIDENCE: Level II:
      Prospective cohort study.

PMID- 29338333
TI  - Endoscopic Transfer of Flexor Hallucis Longus Tendon for Chronic Achilles Tendon
      Rupture: Technical Aspects and Short-Time Experiences.
AB  - BACKGROUND: Chronic Achilles tendon ruptures can lead to reduced power of plantar
      flexion in the ankle with impaired gait ability. The open 1- or 2-incision
      technique for flexor hallucis longus transfer has proven good functional outcome
      but has the disadvantage of relatively extensive surgery performed at a
      vulnerable location. To reduce the risk of soft tissue problems, the flexor
      hallucis longus transfer can be performed endoscopically. MATERIAL AND METHOD: An
      endoscopic technique for flexor hallucis longus transfer is presented together
      with the experiences from the first six patients operated with this method.
      RESULTS: No wound healing problems or infections. Five of 6 patients managed
      single leg heel raise on the affected side 12 months after surgery. CONCLUSION:
      The functional results are promising. The soft tissue dissection is minor, and no
      patients had postoperative wound healing problems or infection. Endoscopic flexor
      hallucis longus transfer may be an operative procedure that can be considered
      also in patients with potential wound healing problems. LEVELS OF EVIDENCE: Level
      IV: Technical note/case series without controls.

PMID- 29338334
TI  - Proximal to Distal Exostectomy for the Treatment of Insertional Achilles
      Tendinopathy.
AB  - : When insertional Achilles tendinopathy is addressed surgically via a central
      Achilles splitting approach, the calcaneal osteotomy has classically been
      performed from distal to proximal. We describe a simple proximal to distal
      technique that allows optimal resection of both the calcaneal exostosis and
      Achilles enthesophyte, minimizes risk to the soft tissues and skin, provides a
      bony attachment surface parallel to the axis of the Achilles tendon, and avoids
      the risk of osteotomy extension into the subtalar joint. LEVELS OF EVIDENCE:
      Level V: Technique tip.

PMID- 29338335
TI  - Diabetic Retinopathy and the Cascade into Vision Loss.
AB  - Vision loss from diabetic retinopathy should be unnecessary for patients with
      access to diabetic retinopathy screening, yet it still occurs at high rates and
      in varied contexts. Precisely because vision loss is only one of many late-stage
      complications of diabetes, interfering with the management of diabetes and making
      self-care more difficult, Vision Threatening Diabetic Retinopathy (VTDR) is
      considered a "high stakes" diagnosis. Our mixed-methods research addressed the
      contexts of care and treatment seeking in a sample of people with VTDR using
      safety-net clinic services and eye specialist referrals. We point to conceptual
      weaknesses in the single disease framework of health care by diagnosis, and we
      use the framework of "cascades" to clarify why and how certain non-clinical
      factors come to bear on long-term experiences of complex chronic diseases.

PMID- 29338336
TI  - Changes in microbial growth, carotenoids, and water-soluble tannin content of
      ripe persimmon beverage after ultra-high pressure treatment.
AB  - To avoid the loss of carotenoids and increasing the tannin content associated
      with pasteurization, we tested ultra-high pressure treatment of ripe persimmon
      beverage. We compared microbial counts (aerobic bacteria, coliforms, and mould),
      carotenoid contents, and water-soluble tannin contents between heat- and ultra
      high pressure-treated beverages. No microbial contamination was detected after
      pasteurization or ultra-high pressure treatment at 400 MPa for more than 5 min.
      Ultra-high pressure treatment significantly prevented the reduction in
      carotenoids (lutein, zeaxanthin, beta-cryptoxanthin, beta-carotene, lycopene),
      with losses of 3.9-28.7%, as compared to the 65% loss after pasteurization.
      Moreover, ultra-high pressure did not induce an increase in water-soluble tannin,
      which causes astringent taste, whereas water-soluble tannins were increased three
      times by heat treatment. In conclusion, ultra-high pressure showed the same
      microbial control effect as pasteurization, while it did not cause carotenoid
      degeneration and increased tannin and thus, it better maintained the quality of
      ripe persimmon beverage.

PMID- 29338337
TI  - Significance of combined preoperative serum Alb and dNLR for diagnosis of
      pancreatic cancer.
AB  - AIM: To investigate diagnostic value of preoperative inflammatory biomarkers in
      pancreatic cancer (PCC). MATERIALS & METHODS: Preoperative circulating Alb/Fib
      ratio, neutrophil/lymphocyte ratio (NLR), derived NLR (dNLR), platelet/lymphocyte
      ratio and lymphocyte/monocyte ratio were detected and calculated in 226 PCC
      individuals, 232 healthy controls and 142 additional cancer controls. Receiver
      operating characteristic curve and area under the curve (AUC) were used to
      evaluate the diagnostic efficacy of PCC. RESULTS: Combined circulating dNLR and
      Alb could effectively improve the diagnosis of PCC (AUC = 0.931), single dNLR
      could distinguish early-stage PCC and the disease from healthy controls (AUC =
      0.895) and additional cancer controls (AUC = 0.794). CONCLUSION: Circulating dNLR
      was an effective biomarker for diagnosis and identification of early-stage PCC.
      Combined dNLR and Alb could improve the diagnostic efficacy of the disease.

PMID- 29338339
TI  - Some Management Information Issues in Indigenous Health.

PMID- 29338338
TI  - Sesbagrandiflorain A and B: isolation of two new 2-arylbenzofurans from the stem
      bark of Sesbania grandiflora.
AB  - Native to tropical Asia, Sesbania grandiflora (L.), Pers is a member of the
      Fabaceae family of flowering plants. All parts of S. grandiflora are used in
      traditional medicine and phytochemical investigations have been conducted on
      extracts of the leaves, seeds and roots of S. grandiflora to provide scientific
      validation of its properties. However, to date, no study has determined the
      phytochemical constituents of S. grandiflora stem bark. The stem bark powdered of
      S. grandiflora was extracted exhaustively with n-hexane, EtOAc and 90% aqueous
      MeOH sequentially. In this study, we successfully isolated two new 2
      arylbenzofurans, sesbagrandiflorain A and B, from the EtOAc stem bark of S.
      grandiflora. The structure elucidation of these compounds was determined by using
      one- and two-dimensional nuclear magnetic resonance, ultraviolet and infrared
      spectroscopy and electrospray ionisation time-of-flight mass spectrometry. The
      finding expands the understanding of the natural constituents of the Fabaceae
      and, in particular, the Papilionoideae genera.

PMID- 29338340
TI  - The ICD-10-AM Mental Health Manual: An Integrated Classification and Diagnostic
      Tool for Community-Based Mental Health Services.

PMID- 29338342
TI  - President's Report.

PMID- 29338341
TI  - RNA sequencing on Amomum villosum Lour. induced by MeJA identifies the genes of
      WRKY and terpene synthases involved in terpene biosynthesis.
AB  - Amomum villosum Lour. is an important Chinese medicinal plant that has diverse
      medicinal functions, and mainly contains volatile terpenes. This study aims to
      explore the WRKY transcription factors (TFs) and terpene synthase (TPS) unigenes
      that might be involved in terpene biosynthesis in A. villosum, and thus providing
      some new information on the regulation of terpenes in plants. RNA sequencing of
      A. villosum induced by methyl jasmonate (MeJA) revealed that the WRKY family was
      the second largest TF family in the transcriptome. Thirty-six complete WRKY
      domain sequences were expressed in response to MeJA. Further, six WRKY unigenes
      were highly correlated with eight deduced TPS unigenes. Ultimately, we combined
      the terpene abundance with the expression of candidate WRKY TFs and TPS unigenes
      to presume a possible model wherein AvWRKY61, AvWRKY28, and AvWRKY40 might
      coordinately trans-activate the AvNeoD promoter. We propose an approach to
      further investigate TF unigenes that might be involved in terpenoid biosynthesis,
      and identified four unigenes for further analyses.

PMID- 29338343
TI  - Molecular analysis of anthocyanin biosynthesis pathway genes and their
      differential expression in mango peel.
AB  - Mango fruit is cherished by masses for its taste and nutrition, contributed by
      color, flavor, and aroma. Among these, peel color is an important trait
      contributing to fruit quality and market value. We attempted to elucidate the
      role of key genes of the anthocyanin biosynthesis pathway related to fruit peel
      color from the leaf transcriptome of mango cultivar Amrapali. A total of 108
      mined transcript sequences were assigned to the phenylpropanoid-flavonoid pathway
      from which 15 contigs representing anthocyanin biosynthesis genes were annotated.
      Alternate splice variants were identified by mapping against genes of Citrus
      clementina and Vitis vinifera (closest relatives) and protein subcellular
      localization was determined. Phylogenetic analysis of these pathway genes
      clustered them into distinct groups aligning with homologous genes of Magnifera
      indica, C. clementina, and V. vinifera. Expression profiling revealed higher
      relative fold expressions in mature fruit peel of red-colored varieties (Arunika,
      Ambika, and Tommy Atkins) in comparison with the green-peeled Amrapali. MiCHS,
      MiCHI, and MiF3H alternate splice variants revealed differential gene expression.
      Functionally divergent variants indicate availability of an allelic pool
      programmed to play critical roles in peel color. This study provides insight into
      the molecular genetic basis of peel color and offers scope for development of
      biomarkers in varietal improvement programs.

PMID- 29338345
TI  - Effect of Anacardium occidentale leaf extract on human acute lymphoblastic
      leukaemia cell lines.
AB  - Anacardium occidentale leaves are used in folk medicine due its therapeutic
      properties attributed to phenolic compounds. Therefore, this study was undertaken
      on its hydroethanolic leaf extract (AoHE) to evaluate cytotoxicity and apoptosis
      induction on acute lymphoblastic leukaemia cells. Results indicated that AoHE
      interfered in the cell cycle progression, inducing apoptosis by activation of
      casp3 at lower concentrations, thence, a promising candidate for the development
      of new cancer drugs.

PMID- 29338344
TI  - Reappraisal inventiveness: impact of appropriate brain activation during efforts
      to generate alternative appraisals on the perception of chronic stress in women.
AB  - BACKGROUND AND OBJECTIVES: Previous research indicated that more left-lateralized
      prefrontal activation during cognitive reappraisal efforts was linked to a
      greater capacity for generating reappraisals, which is a prerequisite for the
      effective implementation of cognitive reappraisal in everyday life. The present
      study examined whether the supposedly appropriate brain activation is relevant in
      terms of more distal outcomes, i.e., chronic stress perception. DESIGN AND
      METHODS: Prefrontal EEG alpha asymmetry was recorded while female participants
      were generating reappraisals for stressful events and was correlated with their
      self-reported chronic stress levels in everyday life (n = 80). RESULTS: Women
      showing less left-lateralized brain activity in the ventrolateral prefrontal
      cortex during cognitive reappraisal efforts reported experiencing more stress in
      their daily lives. This effect was independent of self-efficacy beliefs in
      managing negative emotions. CONCLUSION: These findings underline the practical
      relevance of individual differences in appropriate brain activation during
      emotion regulation efforts and the assumedly related basic capacity for the
      generation of cognitive reappraisals to the feeling of being stressed.
      Implications include the selection of interventions for the improvement of coping
      with stress in women in whom the capability for appropriate brain activation
      during reappraisal efforts may be impaired, e.g., due to depression or old age.

PMID- 29338346
TI  - Foot Mobility Magnitude and Stiffness in Children With and Without Calcaneal
      Apophysitis.
AB  - BACKGROUND: This study evaluated quasi-static measures of foot mobility magnitude
      (FMM) and foot stiffness (FS) in children, aged 8 to 14 years, with and without
      calcaneal apophysitis. METHODS: Between 2016 and 2017, FMM and FS measurements
      were captured on 41 children (22 cases and 19 controls) using a custom-built foot
      assessment platform. The platform incorporated a portable force plate that
      allowed quantification of vertical force during double-limb stance (DLS).
      RESULTS: There was no significant difference in FS in children with and without
      calcaneal apophysitis ( P = .459). FMM was significantly greater (+19%) in
      children with calcaneal apophysitis than in those without ( P = .045). The mean
      difference in FMM between groups (1.4 mm), however, did not exceed the minimum
      detectable change at the 95% confidence level (MDC95%) for the measurement (+/
      2.5 mm). CONCLUSION: Differences in FMM in children with calcaneal apophysitis
      were small and within the observed error of measurement. Clinical measures of FS
      did not differ in children with and without calcaneal apophysitis during
      quasistatic loading. Further research evaluating the level of uncertainty of the
      measurement techniques in children and under dynamic loading conditions is
      recommended. These findings question the rationale behind interventions which aim
      to modify quasistatic foot mobility and stiffness in children with calcaneal
      apophysitis. LEVEL OF EVIDENCE: Level III, comparative series.

PMID- 29338347
TI  - Developments and Issues in ePrescribing and eHealth.

PMID- 29338348
TI  - Links to Cyber Health: Government Web Sites, Australia.

PMID- 29338349
TI  - A multistep docking and scoring protocol for congeneric series: Implementation on
      kinase DFG-out type II inhibitors.
AB  - AIM: Rescoring of docking-binding poses can significantly improve molecular
      docking results. Our aim was to evaluate postprocessing docking protocols in
      order to determine the most suitable methodology for the study of the binding of
      congeneric compounds to protein kinases. MATERIALS & METHODS: Diverse ligand
      receptor poses generated after docking were submitted to different relaxation
      protocols. The Molecular Mechanics Poisson-Boltzmann (Generalized Born) Surface
      Area approach was applied for the evaluation of the binding affinity of complexes
      obtained. The performance of various Molecular Mechanics Poisson-Boltzmann
      (Generalized Born) Surface Area methodologies was compared. RESULTS: The
      inclusion of a postprocessing protocol after docking enhances the quality of the
      results, although the best methodology is system dependent. CONCLUSION: An
      examination of the interactions established has allowed us to suggest useful
      modifications for the design of new type II inhibitors.

PMID- 29338350
TI  - Polyketides from the fungus Penicillium decumbens.
AB  - Two new polyketides, 3,11-dihydroxy-6,8-dimethyldodecanoic acid (1) and
      trichopyrone B (2), together with two known polyketides, sorbicillin (3) and
      penicillone A (4), have been isolated from the cultures broth of the fungus
      Penicillium decumbens. Their structures were elucidated by extensive
      spectroscopic analysis. All isolated compounds were evaluated for their
      antibacterial and cytotoxic activities. Of these, compound 3 showed antifungal
      activity toward Candida albicans Y0109 with a MIC value of 50 MUM. Moreover,
      compounds 3 and 4 exhibited selective cytotoxicity against the human
      hepatocellular carcinoma (QGY-7703) cell line with the IC50 values of 32.5 and
      22.8 MUM, respectively.

PMID- 29338351
TI  - A new lindenane-type sesquiterpenoid lactone from Chloranthus japonicus.
AB  - Chromatographic fractionation of the EtOH extracts of the Traditional Chinese
      Medicine (TCM) Chloranthus japonicus, has led to the isolation of a new lindenane
      type sesquiterpenoid lactone derivative (1). Rosmarylchloranthalactone E (1),
      which consists of lindenane sesquiterpenoid lactone and rosmarinic acid moieties
      linked via an ester bridge, was structurally elucidated by 1D and 2D NMR and HRMS
      data. Compound 1 was a potent phosphodiesterase-4 (PDE4) inhibitor with an IC50
      value of 0.96 +/- 0.04 MUM.

PMID- 29338352
TI  - Anti-inflammatory and antioxidant activities of Rungia congoensis, a traditional
      vegetable consumed by Yombe people from Kongo Central area (DR. Congo).
AB  - Rungia congoensis, a traditional vegetable from Kongo Central area (DR. Congo)
      was studied for establishing microscopic characters and characterised by
      chromatographic techniques and their in vitro biochemical activities against ROS
      production were evaluated in cellular models and on an enzyme, myeloperoxidase
      (MPO), involved in inflammation. Microscopically leaf can be characterised by non
      glandular and glandular trichomes, sinuous anticlinal epidermal cells, diacytic
      stomata and helical vessels. Methanolic extract displayed high cellular
      antioxidant activity at the concentrations range of 0.1-10 MUg mL-1 and 1-20 MUg
      mL-1 using lucigenin on neutrophils and DCFH-DA on HL 60, respectively. This
      extract also showed, more efficient effects on extracellular and intracellular
      ROS production and MPO activity. Antioxidant and anti-inflammatory activities of
      R. congoensis were significantly higher, positively correlated with their
      phytochemical constituents such as flavonoids, iridoids and phenolic acids; and
      could justify their use as traditional vegetable and potent local nutraceutical
      resource.

PMID- 29338353
TI  - Developing a Tailored Website for Promoting Awareness about Obstructive Sleep
      Apnea (OSA) Among Blacks in Community-Based Settings.
AB  - Blacks are at greater risk for lower sleep quality and higher risk for
      obstructive sleep apnea (OSA) than other racial groups. In this study, we
      summarize the development of a tailored website including visuals, key messages,
      and video narratives, to promote awareness about sleep apnea among community
      dwelling blacks. We utilized mixed methods, including in-depth interviews,
      usability-testing procedures, and brief surveys (n = 9, 55% female, 100% black,
      average age 38.5 years). Themes from the qualitative analysis illuminated varied
      knowledge regarding OSA symptoms and prevalent self-reported experience with
      sleep disturbance and OSA symptoms (e.g., snoring). On a scale from 1 (not at
      all) to 5 (very high), participants provided favorable ratings of website
      usefulness (mean = 4.9), user friendliness (mean = 4.9) and attractiveness (mean
      = 4.3). Our findings suggest although tailored health communication has potential
      for serving as a tool for advancing health equity, usability-testing of health
      materials is critical to ensure that culturally and linguistically tailored
      messages are acceptable and actionable in the intended population.

PMID- 29338354
TI  - Teaching and Learning Across Two Cultures and Two Languages: German Health
      Classification and Casemix Education Program.

PMID- 29338356
TI  - Privacy Update: Community Attitudes towards Privacy.

PMID- 29338355
TI  - New compounds with antimicrobial activities from Elaeodendron buchananii stem
      bark.
AB  - The plant species Elaeodendron buchananii Loes is widely used in folklore
      medicine to manage microbial infections in Kenya. Previous studies on the plant
      fruits and root bark revealed the presence of steroids and terpenoids. The
      present phytochemical analysis of the plant stem bark has led to the isolation of
      four new triterpenes characterized as methyl 3beta-acetoxy-11alpha, 19alpha, 28
      trihydroxyurs-12-en-23-oic acid (1), 3beta, 11alpha, 19alpha-trihydroxyurs-12-en
      23, 28-dioic acid (2), 3beta-acetoxy-19alpha, 23, 28-trihydroxyurs-12-ene (3) and
      3-oxo-19alpha, 28-dihydroxyurs-12-en-24-oic acid (4), together with ten known
      ones (5-14), whose structures were elucidated using spectroscopic techniques. The
      isolate canophyllol (8) showed promising antibacterial activity against N.
      meningitides with MIC value of 31.25 MUg/ml.

PMID- 29338357
TI  - Clinical Terminologies, Health Classifications and the Health Information
      Management Profession: Vital to All Sectors of the Healthcare System.

PMID- 29338358
TI  - Chemical and Biological insights of Ouratea hexasperma (A. St.-Hil.) Baill.: a
      source of bioactive compounds with multifunctional properties.
AB  - The study aimed to evaluate in vitro antioxidant, anticholinesterase and
      antidiabetic properties of Ouratea hexasperma (A. St.-Hil.) Baill. The
      inflorescence methanol extract and the ethyl acetate fraction of leaves and stems
      reported the highest Relative Antioxidant Capacity Index (RACI), whereas the
      dichloromethane fraction of leaves was the best inhibitor of alpha-amylase and
      alpha-glucosidase. Trans-3-O-methyl-resveratrol-2-C-beta-glucoside,
      lithospermoside, 2,5-dimethoxy-p-benzoquinone, lup-20(30)-ene-3beta,28-diol, 7-O
      methylgenistein, apigenin and luteolin and amentoflavone were isolated from O.
      hexasperma. Resveratrol derivative was isolated for the first time in Ochnaceae
      family. Luteolin, followed by apigenin, reported the highest Relative Antioxidant
      Capacity Index and they were also the best inhibitors of alpha-glucosidase
      enzyme.

PMID- 29338359
TI  - Characterization of moso bamboo (Phyllostachys edulis) Dof transcription factors
      in floral development and abiotic stress responses.
AB  - The Dof transcription factor (TF) family belongs to a class of plant-specific TFs
      and is involved in plant growth, development, and response to abiotic stresses.
      However, there are only very limited reports on the characterization of Dof TFs
      in moso bamboo (Phyllostachys edulis). In the present research, PheDof TFs showed
      specific expression profiles based on RNA-seq data analyses. The co-expression
      network indicated that PheDof12, PheDof14, and PheDof16 might play vital roles
      during flower development. Cis-regulatory element analysis of these PheDof genes
      suggested diverse functions. Expression patterns of 12 selected genes from seven
      different classes under three abiotic stresses (cold, salt, and drought) are
      further investigated by quantitative real-time PCR. This work will provide useful
      information for functional analysis and regulation mechanisms of Dof TFs in moso
      bamboo.

PMID- 29338361
TI  - Pursue the Challenge: A New Graduate's Experience.

PMID- 29338360
TI  - The Implementation of New Morbidity Classifications in Canada.
AB  - Canada is in the midst of a staggered implementation of the International
      Statistical Classification of Diseases and Related Health Problems, Tenth
      Revision, Canada (ICD-10-CA) and the Canadian Classification of Health
      Interventions (CCI). These classifications are more comprehensive than historical
      standards and their capacity extends beyond the scope of their predecessor
      classifications. Canada is the first country to produce the new classifications
      in a database, with the final product in an infobase format. The Canadian
      Institute for Health Information (CIHI) was responsible for the enhancement of
      ICD-10-CA, the development of CCI, the education of coders, and the provision of
      post-implementation support.

PMID- 29338362
TI  - Coder Educator: The Way Forward.
AB  - The introduction of a new Coder Educator position in the Coding Unit at the
      Princess Alexandra Hospital, Brisbane, Queensland, has been a key strategy in the
      development and maintenance of a skilled coding workforce, the improvement of the
      level of knowledge of the coding staff, and the provision of a career structure
      for clinical coders. In this report, the experience is related from the
      perspectives of the Coding Manager and the Coder Educator.

PMID- 29338363
TI  - The Impact of the Technical/Technological Background of Medical and Paramedical
      Staff on the Efficiency of a Digital Medical Information System Introduced at a
      State Hospital Department.

PMID- 29338364
TI  - Implementation of Privacy Legislation and Principles: A Private Hospital
      Perspective.

PMID- 29338365
TI  - Developing and Managing the National Coroners' Information System for Australia.

PMID- 29338366
TI  - Risk Management - What's in it for Health Information Managers?

PMID- 29338367
TI  - Making a Quality Start: A Coder Orientation Program.
AB  - Orienting new clinical coders to the hospital's case mix should be a basic
      function of the organisation's Coding Service. After much trial and error,
      Southern Health Coding and Casemix Services has devised an orientation program
      that brings together, in a structured and logical manner, all the elements a
      coder needs to know. This article describes the current coding orientation
      program.

PMID- 29338368
TI  - An Australian Standard for Health Care Client Identification.

PMID- 29338370
TI  - The Statewide Client Registration Project Initiated by the Tasmanian Department
      of Health & Human Services.

PMID- 29338369
TI  - Snomed(r) CT: The Fit with Classification in Health.
AB  - Classification systems are the primary means for automated retrieval and analysis
      of healthcare data from individual patient medical records. This article will
      provide a brief history and overview of the two most comprehensive and advanced
      controlled clinical terminologies in the world: the Systematized Nomenclature of
      Medicine Reference Terminology (SNOMED(r) RT), and Clinical Terms Version 3
      (CTV3). A discussion will follow of the merger of these two terminologies into a
      single new work, SNOMED(r) Clinical Terms (SNOMED(r) CT), as released in early
      2002, how it is used to retrieve data, how it differs from a classification, and
      the opportunities open to health information management professionals to expand
      their roles as information managers through their knowledge of SNOMED CT.

PMID- 29338371
TI  - Health Information Services in the West Pilbara Health Service, North-Western
      Australia.

PMID- 29338372
TI  - Getting it Right: Meeting the Aged Care Accreditation Standards.
AB  - The aged care industry in Australia has been faced with many challenges over the
      last five years, including the introduction of the Aged Care Act 1997 and the
      Aged Care Accreditation Standards. The purpose of the introduction of the
      accreditation process was to ensure that residential aged care services were
      complying with the Accreditation Standards and making a commitment to
      continuously improve their standard of care and services (Aged Care Standards and
      Accreditation Agency, 2000). This article describes how one service has
      implemented a management system approach to ensure compliance with the Aged Care
      Accreditation Standards.

PMID- 29338373
TI  - Nursing Classification and Terminology Systems.
AB  - A number of terminologies exist that represent concepts of relevance to nurses,
      although none of these is in use by Australian nurses. Without consensus, nursing
      language and definitions incorporated in clinical information systems now being
      implemented will continue to vary considerably. The result will be an inability
      to compare nursing practice, or to aggregate data for research purposes, or to
      collect national statistical data to demonstrate the significance of nurses'
      contributions to health care. This article provides an international historical
      overview of nursing terminology developments relative to what is happening in
      Australia, brief reviews of the many available nursing terminologies, an update
      of this work relative to activities being undertaken towards the development and
      adoption of standards, and a discussion about desirable future research and
      development activities.

PMID- 29338374
TI  - Accreditation in Primary Health: RACGP Standards for General Practice.
AB  - General Practitioners play a crucial role as "gate-keepers" to the health system.
      In this context, they have a profound influence on both health outcomes and
      health expenditure. Since the introduction in 1999 of a formal, peer-driven
      external accreditation process, over 4,590 Australian general practices have
      achieved full accreditation. The process of re-ccreditation has commenced,
      subsequent to a review of the original standards, and with an ongoing focus on
      continuous quality improvement. This article describes a typical accreditation
      survey visit, and explains the accreditation criteria and how they are reviewed
      by the surveyors. There is discussion also of the impact of this new
      accreditation system on general practice.

PMID- 29338375
TI  - Information and Case Mix Funding.

PMID- 29338376
TI  - Australian Classification of Health Interventions - Adapted for International Use
      (ACHI-I).

PMID- 29338377
TI  - The Research and Public Consultation Process Undertaken in the Development of AR
      DRG Version 5.0.

PMID- 29338378
TI  - Health Information Management in the Australian Health Care System as a Whole.

PMID- 29338379
TI  - Factors Affecting Survival in Children With Pericardial Effusion After
      Hematopoietic Stem Cell Transplantation.
AB  - The objective of this study was to determine the incidence, risk factors,
      outcome, and clinical significance of pericardial effusion (PE). We
      retrospectively analyzed outcomes of 272 pediatric patients undergoing their
      first hematopoietic stem cell transplantation (HSCT) from 1998 to 2016. In total,
      15% (3/20) and 5.9% (15/252) of autologous and allogeneic HSCT recipients,
      respectively, were identified with PE. However, there was no statistically
      significant difference in the incidence of PE between the 2 groups. The mean age
      at transplantation was 11.12 +/- 5.41 y. Eighteen patients developed PE at 4.13
      +/- 4.44 mo after HSCT. PE was confirmed by echocardiogram in all patients. Three
      patients presented with severe PE with cardiac tamponade and required urgent
      pericardiocentesis. Overall survival (OS) rates for patients who developed PE
      were 83.3% and 38.9% at 100 d and 3 y, respectively, after HSCT. Death was not
      directly attributable to PE in patients who died in the first year after HSCT.
      Multivariable analysis identified the following variables to be associated with
      OS: PE (relative risk[RR]: 3.70; 95% confidence interval [95% CI]: 1.89-7.23; P <
      0.001), active disease at HSCT (RR: 1.59; 95% CI: 1.02-2.49; P < 0.001), and
      thalassemia (RR: 0.62; 95% CI: 0.45-0.84; P < 0.001). PE is, thus, a debilitating
      and significant complication of pediatric HSCT. Therefore, prospective studies
      are required for better determination of the etiology and optimal method of PE
      treatment after HSCT.

PMID- 29338380
TI  - Transplantation of Human Neural Progenitor Cells Reveals Structural and
      Functional Improvements in the Spastic Han-Wistar Rat Model of Ataxia.
AB  - The use of regenerative medicine to treat nervous system disorders like ataxia
      has been proposed to either replace or support degenerating neurons. In this
      study, we assessed the ability of human neural progenitor cells (hNPCs) to repair
      and restore the function of dying neurons within the spastic Han-Wistar rat
      (sHW), a model of ataxia. The sHW rat suffers from neurodegeneration of specific
      neurons, including cerebellar Purkinje cells and hippocampal CA3 pyramidal cells
      leading to the observed symptoms of forelimb tremor, hind-leg rigidity, gait
      abnormality, motor incoordination, and a shortened life span. To alleviate the
      symptoms of neurodegeneration and to replace or augment dying neurons, neuronal
      human progenitor cells were implanted into the sHW rats. At 30 d of age, male sHW
      mutant rats underwent subcutaneous implantation of an Alzet osmotic pump that
      infused cyclosporine (15 mg/kg/d) used to suppress the rat's immune system. At 40
      d, sHW rats received bilateral injections (500,000 cells in 5 uL media) of live
      hNPCs, dead hNPCs, live human embryonic kidney cells, or growth media either into
      the cerebellar cortex or into the hippocampus. To monitor results, motor activity
      scores (open-field testing) and weights of the animals were recorded weekly. The
      sHW rats that received hNPC transplantation into the cerebellum, at 60 d of age,
      displayed significantly higher motor activity scores and sustained greater
      weights and longevities than control-treated sHW rats or any hippocampal
      treatment group. In addition, cerebellar histology revealed that the transplanted
      hNPCs displayed signs of migration and signs of neuronal development in the
      degenerated Purkinje cell layer. This study revealed that implanted human
      progenitor cells reduced the ataxic symptoms in the sHW rat, identifying a future
      clinical use of these progenitor cells against ataxia and associated
      neurodegenerative diseases.

PMID- 29338381
TI  - Effect of the Diabetic State on Islet Engraftment and Function in a Large Animal
      Model of Islet-Kidney Transplantation.
AB  - In islet transplantation, in addition to immunologic and ischemic factors, the
      diabetic/hyperglycemic state of the recipient has been proposed, although not yet
      validated, as a possible cause of islet toxicity, contributing to islet loss
      during the engraftment period. Using a miniature swine model of islet
      transplantation, we have now assessed the effect of a persistent state of
      hyperglycemia on islet engraftment and subsequent function. An islet-kidney (IK)
      model previously described by our laboratory was utilized. Three experimental
      donor animals underwent total pancreatectomy and autologous islet transplantation
      underneath the renal capsule to prepare an IK at a load of <=1,000 islet
      equivalents (IE)/kg donor weight, leading to a chronic diabetic state during the
      engraftment period (fasting blood glucose >250 mg/dL). Three control donor
      animals underwent partial pancreatectomy (sufficient to maintain normoglycemia
      during islet engraftment period) and IK preparation. As in vivo functional
      readout for islet engraftment, the IKs were transplanted across an immunologic
      minor or class I mismatch barrier into diabetic, nephrectomized recipients at an
      islet load of ~4,500 IE/kg recipient weight. A 12-d course of cyclosporine was
      administered for tolerance induction. All experimental donors became diabetic and
      showed signs of end organ injury, while control donors maintained normoglycemia.
      All recipients of IK from both experimental and control donors achieved glycemic
      control over long-term follow-up, with reversal of diabetic nephropathy and with
      similar glucose tolerance tests. In this preclinical, large animal model, neither
      islet engraftment nor subsequent long-term islet function after transplantation
      appear to be affected by the diabetic state.

PMID- 29338382
TI  - Mounting of Biomaterials for Use in Ophthalmic Cell Therapies.
AB  - When used as scaffolds for cell therapies, biomaterials often present basic
      handling and logistical problems for scientists and surgeons alike. The quest for
      an appropriate mounting device for biomaterials is therefore a significant and
      common problem. In this review, we provide a detailed overview of the factors to
      consider when choosing an appropriate mounting device including those experienced
      during cell culture, quality assurance, and surgery. By way of example, we draw
      upon our combined experience in developing epithelial cell therapies for the
      treatment of eye diseases. We discuss commercially available options for
      achieving required goals and provide a detailed analysis of 4 experimental
      designs developed within our respective laboratories in Australia, the United
      Kingdom, and Belgium.

PMID- 29338383
TI  - The Process of Engraftment of Myogenic Cells in Skeletal Muscles of Primates:
      Understanding Clinical Observations and Setting Directions in Cell
      Transplantation Research.
AB  - We studied in macaques the evolution of the intramuscular transplantation of
      muscle precursor cells between the time of administration and the time at which
      the graft is considered stable. Satellite cell-derived myoblasts labeled with
      beta-galactosidase were transplanted into 1 cm3 muscle regions following cell
      culture and transplantation protocols similar to our last clinical trials. These
      regions were biopsied 1 h, 1, 3, 7 d, and 3 wk later and analyzed by histology.
      We observed that the cell suspension leaks from the muscle bundles during
      injection toward the epimysium and perimysium, where most cells accumulate after
      transplantation. We observed evidence of necrosis, apoptosis, and mitosis in the
      accumulations of grafted cells, and of potential migration to participate in
      myofiber regeneration in the surrounding muscle bundles. After 3 wk, the compact
      accumulations of grafted cells left only some graft-derived myotubes and small
      myofibers in the perimysium. Hybrid myofibers were abundant in the muscle
      fascicles at 3 wk posttransplantation, and they most likely occur by grafted
      myoblasts that migrated from the peripheral accumulations than by the few
      remaining within the fascicles immediately after injection. These observations
      explain the findings in clinical trials of myoblast transplantation and provide
      information for the future research in cell therapy in myology.

PMID- 29338384
TI  - Human Umbilical Cord Mesenchymal Stem Cells Preserve Adult Newborn Neurons and
      Reduce Neurological Injury after Cerebral Ischemia by Reducing the Number of
      Hypertrophic Microglia/Macrophages.
AB  - Microglia are the first source of a neuroinflammatory cascade, which seems to be
      involved in every phase of stroke-related neuronal damage. Two weeks after
      transient middle cerebral artery occlusion (MCAO), vehicle-treated rats displayed
      higher numbers of total ionized calcium-binding adaptor molecule 1 (Iba-1)
      positive cells, greater cell body areas of Iba-1-positive cells, and higher
      numbers of hypertrophic Iba-1-positive cells (with a cell body area over 80 MUm2)
      in the ipsilateral ischemic brain regions including the frontal cortex, striatum,
      and parietal cortex. In addition, MCAO decreased the number of migrating
      neuroblasts (or DCX- and 5-ethynyl-2'-deoxyuridine-positive cells) in the cortex,
      subventricular zone, and hippocampus of the ischemic brain, followed by
      neurological injury (including brain infarct and neurological deficits).
      Intravenous administration of human umbilical cord-derived mesenchymal stem cells
      (hUC-MSCs; 1 * 106 or 4 * 106) at 24 h after MCAO reduced neurological injury,
      decreased the number of hypertrophic microglia/macrophages, and increased the
      number of newborn neurons in rat brains. Thus, the accumulation of hypertrophic
      microglia/macrophages seems to be detrimental to neurogenesis after stroke.
      Treatment with hUC-MSCs preserved adult newborn neurons and reduced functional
      impairment after transient cerebral ischemia by reducing the number of
      hypertrophic microglia/macrophages.

PMID- 29338385
TI  - Does the Mesenchymal Stem Cell Source Influence Smooth Muscle Regeneration in
      Tissue-Engineered Urinary Bladders?
AB  - A variety of tissue engineering techniques utilizing different cells and
      biomaterials are currently being explored to construct urinary bladder walls de
      novo, but so far no approach is clearly superior. The aim of this study was to
      determine whether mesenchymal stem cells (MSCs) isolated from different sources,
      (bone marrow [BM-MSCs] and adipose tissue [ADSCs]), differ in their potential to
      regenerate smooth muscles in tissue-engineered urinary bladders and to determine
      an optimal number of MSCs for urinary bladder smooth muscle regeneration. Forty
      eight rats underwent hemicystectomy and bladder augmentation with approximately
      0.8 cm2 graft. In the first and second groups, urinary bladders were
      reconstructed with small intestinal submucosa (SIS) seeded with 10 * 106 or 4 *
      106 ADSCs/cm2, respectively. In the third and fourth groups, urinary bladders
      were augmented with SIS seeded with 10 * 106 or 4 * 106 BM-MSCs/cm2,
      respectively. In the fifth group, urinary bladders were augmented with SIS
      without cells. The sixth group (control) was left intact. Smooth muscle
      regeneration was evaluated by real-time polymerase chain reaction (RT-PCR) and
      histological examinations. Histologically, there were no significant differences
      between urinary bladders augmented with ADSCs and BM-MSCs, but there was a marked
      increase in smooth muscle formation in bladders augmented with grafts seeded with
      MSCs in higher density (10 * 106/cm2) compared to lower density (4 * 106/cm2).
      Molecular analysis revealed that bladders reconstructed with ADSC-seeded grafts
      expressed higher levels of smooth muscle myosin heavy chain, caldesmon, and
      vinculin. Bladders augmented with unseeded SIS were fibrotic and devoid of smooth
      muscles. ADSCs and BM-MSCs have comparable smooth muscle regenerative potential,
      but the number of MSCs used for graft preparation significantly affects the
      smooth muscle content in tissue-engineered urinary bladders.

PMID- 29338387
TI  - Quantifying the Effects of Different Neutral Proteases on Human Islet Integrity.
AB  - Efficient islet release from the pancreas requires the combination of
      collagenase, neutral protease (cNP), or thermolysin (TL). Recently, it has been
      shown that clostripain (CP) may also contribute to efficient islet release from
      the human pancreas. The aim of this study was to evaluate the impact of these
      proteases on human islet integrity in a prospective approach. Islets were
      isolated from the pancreas of 10 brain-dead human organ donors. Purified islets
      were precultured for 3 to 4 d at 37  degrees C to ensure that preparations were
      cleared of predamaged islets, and only integral islets were subjected to 90 min
      of incubation at 37  degrees C in Hank's balanced salt solution supplemented with
      cNP, TL, or CP. The protease concentrations were calculated for a pancreas of 100
      g trimmed weight utilizing 120 dimethyl-casein units of cNP, 70,000 caseinase
      units of TL, or 200 benzoyl-l-arginine-ethyl-ester units of CP (1*). These
      activities were then increased both 5* and 10*. After subsequent 24-h culture in
      enzyme-free culture medium, treated islets were assessed and normalized to sham
      treated controls. Compared with controls and CP, islet yield was significantly
      reduced by using the 5* activity of cNP and TL, inducing also fragmentation and
      DNA release. Viability significantly decreased not until adding the 1* activity
      of cNP, 5* activity of TL, or 10* activity of CP. Although mitochondrial function
      was significantly lowered by 1* cNP and 5* TL, CP did not affect mitochondria at
      any concentration. cNP- and TL-incubated islets significantly lost intracellular
      insulin already at 1* activity, while the 10* activity of CP had to be added to
      observe a similar effect. cNP and TL have a similar toxic potency regarding islet
      integrity. CP also induces adverse effects on islets, but the toxic threshold is
      generally higher. We hypothesize that CP can serve as supplementary protease to
      minimize cNP or TL activity for efficient pancreas digestion.

PMID- 29338386
TI  - Estrogen-Estrogen Receptor alpha Signaling Facilitates Bilirubin Metabolism in
      Regenerating Liver Through Regulating Cytochrome P450 2A6 Expression.
AB  - BACKGROUND: After living donor liver transplantation (LDLT), rising serum
      bilirubin levels commonly indicate insufficient numbers of hepatocytes are
      available to metabolize bilirubin into biliverdin. Recovery of bilirubin levels
      is an important marker of hepatocyte repopulation after LDLT. Cytochrome P450
      (CYP) 2A6 in humans (or cyp2a4 in rodents) can function as "bilirubin oxidase."
      Functional hepatocytes contain abundant CYP2A6, which is considered a marker for
      hepatocyte function recovery. The aim of our study was to determine the impact of
      estradiol/estrogen receptor signaling on bilirubin levels during liver function
      recovery. METHODS: We conducted a hospital-based cohort study of bilirubin levels
      after LDLT surgery in both liver graft donors and recipients, performed a
      transcriptome comparison of wild-type versus estrogen receptor (ER)alpha knockout
      mice and a bioinformatics analysis of transcriptome changes in their regenerating
      liver after two-third partial hepatectomy (PHx), and assayed in vitro expression
      of cytochrome (CYP2A6) in human hepatic progenitor cells (HepRG) treated with
      17beta-estradiol (E2). RESULTS: The latency of bilirubin level reduction was
      shorter in women than in men, suggesting that a female factor promotes bilirubin
      recovery after liver transplantation surgery. In the PHx mouse model, the
      expression of the cyp2a4 gene was significantly lower in livers from the knockout
      ERalpha mice than in livers from their wild-type littermates; but the expression
      of other bilirubin metabolism-related genes were similar between these groups.
      Moreover, E2 or bilirubin treatments significantly promoted CYP2A6 expression in
      hepatocyte progenitor cells (HepRG cells). Sequence analysis revealed similar
      levels of aryl hydrocarbon receptor (AhR; bilirubin responsive nuclear receptor)
      and ESR1 binding to the promoter region of CYP2A6. CONCLUSIONS: This is the first
      report to demonstrate, on a molecular level, that E2/ERalpha signaling
      facilitates bilirubin metabolism in regenerating liver. Our findings contribute
      new knowledge to our understanding of why the latency of improved bilirubin
      metabolism and thereby liver function recovery is shorter in females than in
      males.

PMID- 29338389
TI  - Privacy Officer: A Role for Health Information Managers.
AB  - Health information managers (HIMs) are experts in the protection and management
      of health information within patient records and information systems. New privacy
      legislation in Australia has raised the importance of this protection and a new
      role of Privacy Officer is evolving. HIMs are well positioned to take on this
      role and its associated responsibilities. Here, a Privacy Officer from Victoria
      provides an insight into the position and its opportunities.

PMID- 29338391
TI  - Development of a National Standard for the Identification of Health Care
      Providers.

PMID- 29338390
TI  - Preparing for New Health Privacy Legislation in Rural Australia.
AB  - This Rural Professional Practice item describes the benefits of a collaborative,
      regional approach to implementing new health privacy legislation.
      Videoconferencing has been adopted to surmount the problems of long-distance
      communication between the Privacy Officers of 11 regional health services spread
      throughout a large region of south-eastern Australia.

PMID- 29338388
TI  - Novel Fusion Protein Targeting Mitochondrial DNA Improves Pancreatic Islet
      Functional Potency and Islet Transplantation Outcomes.
AB  - Long-term graft survival is an ongoing challenge in the field of islet
      transplantation. With the growing demand for transplantable organs, therapies to
      improve organ quality and reduce the incidence of graft dysfunction are of
      paramount importance. We evaluated the protective role of a recombinant DNA
      repair protein targeted to mitochondria (Exscien I-III), as a therapeutic agent
      using a rodent model of pancreatic islet transplantation. We first investigated
      the effect of therapy on isolated rat islets cultured with pro-inflammatory
      cytokines (interleukin-1 beta, interferon gamma, and tumor necrosis factor alpha)
      for 48 h and documented a significant reduction in apoptosis by flow cytometry,
      improved viability by immunofluorescence, and conserved functional potency in
      vitro and in vivo in Exscien I-III-treated islets. We then tested the effect of
      therapy in systemic inflammation using a rat model of donor brain death (BD)
      sustained for a 6-h period. Donor rats were allocated to 4 groups: (non-BD +
      vehicle, non-BD + Exscien I-III, BD + vehicle, and BD + Exscien I-III) and
      treated with Exscien I-III (4 mg/kg) or vehicle 30 min after BD induction. Sham
      (non-BD)-operated animals receiving either Exscien I-III or vehicle served as
      controls. Islets purified from BD + Exscien I-III-treated donors showed a
      significant increase in glucose-stimulated insulin release in vitro when compared
      to islets from vehicle-treated counterparts. In addition, donor treatment with
      Exscien I-III attenuated the effects of BD and significantly improved the
      functional potency of transplanted islets in vivo. Our data indicate that
      mitochondrially targeted antioxidant therapy is a novel strategy to protect
      pancreas and islet quality from the deleterious effects of cytokines in culture
      and during the inflammatory response associated with donation after BD. The
      potential for rapid translation into clinical practice makes Exscien I-III an
      attractive therapeutic option for the management of brain-dead donors or as an
      additive to islets in culture after isolation setting.

PMID- 29338392
TI  - What is Quality in Health Care?

PMID- 29338393
TI  - Overview of the New South Wales Health Unique Patient Identifier Project.

PMID- 29338394
TI  - Reference Terminologies.

PMID- 29338395
TI  - The University of Sydney, Sydney, New South Wales.

PMID- 29338396
TI  - Queensland University of Technology, Brisbane, Queensland.

PMID- 29338397
TI  - Regarding Questions and Principles.

PMID- 29338398
TI  - Valuing Your Past to Provide a Stronger Future - A Queensland Perspective on
      Professional Development at the State Level.

PMID- 29338399
TI  - The 2nd National Health Online Summit, Brisbane 3-4 March 2003.
AB  - The first conference was held in Adelaide in August 2000. The conference was an
      initiative of the National Health Information Management Advisory Council
      (NHIMAC). NHIMAC was established in 1998 by the Australian Health Ministers to
      advise on options to promote a nationally uniform approach to more effective
      information management in the health sector. The second conference was held in
      Brisbane in March 2003, and this paper provides an overview of the key issues
      addressed there.

PMID- 29338401
TI  - From Shanghai to Guangzhou: Interest in Health Information Management from China.

PMID- 29338400
TI  - Excerpts from the IFHRO Handbook on Health Record Education.

PMID- 29338402
TI  - Research in Health Information Management Practice.

PMID- 29338403
TI  - Guardians of Knowledge: The Paradigm of Confidentiality.

PMID- 29338404
TI  - Understanding Neurobiological Implications of Maltreatment: A focus on children
      and youth.

PMID- 29338405
TI  - Graduate Student/Postdoctoral Fellow Section of Child Maltreatment Editorial
      Board.

PMID- 29338406
TI  - A Decade of the Australian Casemix Classification.

PMID- 29338407
TI  - La Trobe University, Melbourne, Victoria.

PMID- 29338408
TI  - 10th European Conference on Health Records, Dublin, Ireland, 25-29 August 2002:
      Managing Health Information in the 21st Century.

PMID- 29338409
TI  - Announcing: The 14th Congress of the International Federation of Health Records
      Organizations, in Conjunction with the American Health Information Management
      Association 76th National Convention and Exhibit - Washington, DC, USA, 9-14
      October, 2004.

PMID- 29338410
TI  - Uses of Health Information.

PMID- 29338411
TI  - Update from the IFHRO Executive Committee.

PMID- 29338412
TI  - International Reflections.

PMID- 29338413
TI  - HIMAA and Education.

PMID- 29338414
TI  - HIM Education Advances.

PMID- 29338415
TI  - AHIMA Project Offers Insights into SNOMED, ICD-9-CM Mapping Process.

PMID- 29338416
TI  - Data Quality Management at Hong Kong Public Hospitals.

PMID- 29338417
TI  - Editorial.

PMID- 29338418
TI  - Once upon a Time ... the Power of Story and Learning Journals.
AB  - This paper will invite you to consider the role of stories for learning and the
      use of learning journals as a tool to create meaning. The application of story
      and story culture in higher education, academia and management contexts will be
      presented. As an example, an old Punjabi tale will be adapted for use when
      managing and inspiring teams in the workplace. Storytelling is experiencing a
      revival and being used in the corporate sector to ignite action in knowledge-era
      organisations.

PMID- 29338419
TI  - A Review of Health Information Management Education in China.

PMID- 29338421
TI  - A Decade of Casemix Funding in Victoria.

PMID- 29338420
TI  - Curtin University of Technology, Perth, Western Australia.

PMID- 29338422
TI  - Professional Development - South Australian Branch of HIMAA Update.

PMID- 29338424
TI  - International Federation of Health Records Organizations (IFHRO) - Newsletter.

PMID- 29338423
TI  - Production of thermostable multiple enzymes from Bacillus amyloliquefaciens
      KUB29.
AB  - A strain of Bacillus amyloliquefaciens KUB29 was identified by 16S ribosomal RNA
      sequencing (Genbank: MF772779.1). Production of thermostable protease, amylase
      and lipase were done by the isolated strain. The produced enzymes were partially
      purified by ammonium precipitation followed by dialysis process. Protease and
      lipase enzymes are effectively used in bio-oil extraction from proteinaceous
      sample followed by transesterification to produce methyl ester. Amylase enzyme is
      widely used in food and laundry industry. The produced enzymes are active at
      thermophilic condition of 55  degrees C. Use of these enzymes in biofuel
      production process will make the process cleaner and greener.

PMID- 29338425
TI  - Correction: Re: Acknowledgment: A Profile of Coding Staff in Sydney Metropolitan
      Public Hospitals Health Information Management, Vol 32(2).
AB  - The authors would like to thank Adam Bennett, who collected the raw data used in
      this study for his thesis submitted for the degree of Bachelor of Applied Science
      (Health Information Management) (Honours) at The University of Sydney.

PMID- 29338426
TI  - Evolution, Not Revolution: Measurement and Management of Health Outcomes in New
      Zealand through Efficient Use of National Information Systems.
AB  - The development of health information systems is not always successful, and there
      is an emerging perception that money and time that could be better directed to
      patient care are being wasted on these systems. This paper examines the
      difficulties faced in creating successful information systems in health services,
      and suggests strategies for overcoming these difficulties. The development of
      information systems is a precursor to the use of data in the management of
      processes which lead towards improved health outcomes. It is argued that before
      embarking upon difficult and costly new developments, researchers should treat
      existing sources of data as their first point of call, and New Zealand's existing
      national data sources are described in detail. Ways in which these data are being
      used to develop outcome measures are discussed, and it is concluded that through
      a multidisciplinary approach existing resources could be utilised more
      efficiently and effectively to achieve this goal.

PMID- 29338427
TI  - Lipid nanoparticles for intranasal administration: application to nose-to-brain
      delivery.
AB  - INTRODUCTION: The blood brain barrier is a functional barrier allowing the entry
      into the brain of only essential nutrients, excluding other molecules. Its
      structure, although essential to keep the harmful entities out, is also a major
      roadblock for pharmacological treatment of brain diseases. Several alternative
      invasive drug delivery approaches, such as transcranial drug delivery and
      disruption of blood brain barrier have been explored, with limited success and
      several challenges. Intranasal delivery is a non-invasive methodology, which
      bypasses the systemic circulation, and, through the intra- and extra- neuronal
      pathways, provides direct brain drug delivery. Colloidal drug delivery systems,
      particularly lipidic nanoparticles offer several unique advantages for this goal
      . Areas covered: This review focuses on key brain diseases such as Alzheimer's
      disease, Parkinson's disease, Huntington's disease and amyotrophic lateral
      sclerosis, and provide a detailed overview of the current lipid nanoparticle
      based treatment options explored thus far. The review also delves into basic
      preparation, challenges and evaluation methods of lipid drug delivery systems.
      Expert opinion: Brain diseases present complex pathophysiology, in addition to
      the practically inaccessible brain tissues, hence according to the authors, a two
      pronged approach utilizing new target discovery coupled with new drug delivery
      systems such as lipid carriers must be adopted.

PMID- 29338428
TI  - HIMAA President Receives Award.

PMID- 29338429
TI  - Study of aflatoxicosis reduction: effect of Alchornea cordifolia on biomarkers in
      an aflatoxin B1 exposed rats.
AB  - The toxicity of aflatoxins results in cancer and liver disease. Several natural
      substances such as plants exhibited their ability to inhibit the initiation of
      aflatoxin carcinogenesis. The aim of this study was to evaluate the effect of
      Alchornea cordifolia on biomarkers in an aflatoxin B1 (AFB1) exposed rats. The
      contents of polyphenols, flavonoids and the antioxidant activity of A. cordifolia
      ethanolic leaf extract (EELac) were assessed. Groups of rats were treated orally
      with a daily dose of a mixture of AFB1 at a dose of 150 MUg/kg body weight and
      EELac (50, 100 and 300 mg/kg body weight) for 21 days. Biomarkers of AFB1, such
      as the AFB1-lysine adduct and aflatoxin M1 were assayed in blood and urine,
      respectively, using an HPLC system with a fluorescence detector. The contents of
      polyphenols and flavonoids were 6783.23 +/- 272.76 MUg EAG/g and 10.54 +/- 3.15%
      of dry matter, respectively. EELac showed a good antioxidant activity (IC50 =
      12.65 +/- 0.13 MUg/mL). The administration of the mixture (AFB1 + EELac) at
      different doses significantly reduced the level of AFB1-lysine adduct from 14.04
      +/- 2.1 to 4.13 +/- 0.9 ng/mg albumin and that of Aflatoxin M1 (AFM1) from 456 +/
      16 to 220 +/- 24 ng/mL (p <0.05). The rate of reduction was 70.58% for AFB1
      lysine adduct and 51.75% for AFM1. A. cordifolia could be used in the prevention
      of toxicity induced by AFB1 on account of its high content in phenolic compounds.

PMID- 29338430
TI  - State-Level Point-of-Sale Tobacco News Coverage and Policy Progression Over a 2
      Year Period.
AB  - BACKGROUND: Mass media content may play an important role in policy change.
      However, the empirical relationship between media advocacy efforts and tobacco
      control policy success has rarely been studied. We examined the extent to which
      newspaper content characteristics (volume, slant, frame, source, use of evidence,
      and degree of localization) that have been identified as important in past
      descriptive studies were associated with policy progression over a 2-year period
      in the context of point-of-sale (POS) tobacco control. METHOD: We used regression
      analyses to test the relationships between newspaper content and policy
      progression from 2012 to 2014. The dependent variable was the level of
      implementation of state-level POS tobacco control policies at Time 2. Independent
      variables were newspaper article characteristics (volume, slant, frame, source,
      use of evidence, and degree of localization) and were collected via content
      analysis of the articles. State-level policy environment contextual variables
      were examined as confounders. RESULTS: Positive, significant bivariate
      relationships exist between characteristics of news content (e.g., high overall
      volume, public health source present, local quote and local angle present, and
      pro-tobacco control slant present) and Time 2 POS score. However, in a
      multivariate model controlling for other factors, significant relationships did
      not hold. DISCUSSION: Newspaper coverage can be a marker of POS policy
      progression. Whether media can influence policy implementation remains an
      important question. Future work should continue to tease out and confirm the
      unique characteristics of media content that are most associated with subsequent
      policy progression, in order to inform media advocacy efforts.

PMID- 29338432
TI  - Working in Vanuatu.

PMID- 29338431
TI  - Medically induced hypertension, hypervolaemia and haemodilution for the treatment
      and prophylaxis of vasospasm following aneurysmal subarachnoid haemorrhage:
      systematic review.
AB  - PURPOSE: Arterial vasospasm is a major cause of death and long-term disability
      following subarachnoid haemorrhage (SAH). The use of medically induced
      hypertension, hypervolaemia and/or haemodilution is widely practiced for
      prophylaxis and treatment of vasospasm following SAH. We aimed to determine if
      the quality of available research is adequate to inform use of haemodynamic
      management strategies to prevent or treat vasospasm following SAH. METHODS:
      Individual searches of the following databases were conducted: The Cochrane
      Database of Systematic Reviews, The Cochrane Central Register of Controlled
      Trials, MEDLINE, EMBASE and OpenSIGLE. Pertinent randomised clinical trials and
      cohort studies comparing any element or combination thereof: medically induced
      hypertension, hypervolaemia, and haemodilution were included. Data were extracted
      using standardised proformas and risk of bias assessed using a domain-based risk
      of bias assessment tool. RESULTS: 348 study reports were identified by our
      literature search. Eight studies were included, three of which examined both
      volume expansion and medically induced hypertension. Three randomised clinical
      trials and two cohort studies examining prophylactic volume expansion were
      included. Two trials of prophylactic medically induced hypertension and two
      cohort studies were included. One trial and one cohort study of medically induced
      hypertension for treatment of established vasospasm was included. These trials
      demonstrated no significant difference in any of the clinical outcome measures
      studied. No trials of blood transfusion were included. CONCLUSIONS: There is
      currently insufficient evidence to determine the efficacy or non-efficacy of
      intravenous volume expansion, medically induced hypertension or blood transfusion
      for the treatment or prophylaxis of vasospasm following SAH. All of these
      approaches have been associated with adverse events, of unclear incidence. The
      current evidence base therefore cannot be used to reliably inform clinical
      practice. This is a priority for further research.

PMID- 29338433
TI  - In Vivo Ovarian Cancer Gene Therapy Using CRISPR-Cas9.
AB  - Clustered regularly interspaced short palindromic repeats (CRISPR)-caspase 9
      (Cas9) genome editing technology holds great promise for the field of human gene
      therapy. However, a lack of safe and effective delivery systems restricts its
      biomedical application. Here, a folate receptor-targeted liposome (F-LP) was used
      to deliver CRISPR plasmid DNA co-expressing Cas9 and single-guide RNA targeting
      the ovarian cancer-related DNA methyltransferase 1 (DNMT1) gene (gDNMT1). F-LP
      efficiently bound the gDNMT1 plasmid and formed a stable complex (F-LP/gDNMT1)
      that was safe for injection. F-LP/gDNMT1 effectively mutated endogenous DNMT1 in
      vitro, and then expressed the Cas9 endonuclease and downregulated DNMT1 in vivo.
      The tumor growth of both paclitaxel-sensitive and -resistant ovarian cancers were
      inhibited by F-LP/gDNMT1, which shows fewer adverse effects than paclitaxel
      injection. Therefore, CRISPR-Cas9-targeted DNMT1 manipulation may be a potential
      therapeutic regimen for ovarian cancer, and lipid-mediated delivery systems
      represent promising delivery vectors of CRISPR-Cas9 technology for precise genome
      editing therapeutics.

PMID- 29338434
TI  - Standardising Client Identification across Adelaide Public Hospitals - An Update.
AB  - To be able to integrate health information across multiple systems and locations,
      it is essential that the collection and maintenance of key client identifying
      demographic data be standardised. South Australia is now moving towards a
      rigorous approach of client identification across the eight public metropolitan
      hospitals to support the rollout of a clinical information system. The system is
      being implemented for all clinical services and an estimated 8,000 doctors,
      nurses and allied health professionals have been trained in its use. This paper
      discusses the development and scope of a new set of client identification data
      standards (for hospitals only) that have been designed to support this project.

PMID- 29338436
TI  - The Value of Continuing Professional Development.

PMID- 29338435
TI  - Three new diphenyl ether derivatives from the fermentation products of an
      endophytic fungus Phomopsis fukushii.
AB  - Three new diphenyl ethers (1-3), together with four known isopentylated diphenyl
      ethers derivatives (4-7), were isolated from the fermentation products of an
      endophytic fungus Phomopsis fukushii. Their structures were elucidated by
      spectroscopic methods, including extensive 1D and 2D NMR techniques. Compounds 1
      3 were evaluated for their anti-methicillin-resistant Staphylococcus aureus (anti
      MRSA) activity. The results revealed that compounds 1 and 2 showed strong
      inhibitions with inhibition zone diameters (IZD) of 20.2 +/- 2.5 mm and 17.9 +/-
      2.2 mm, respectively. Compound 3 also showed good inhibition with IZD 15.2 +/-
      1.8 mm. The IZD data of compound 1 is close to that of positive control with IZD
      21.9 +/- 2.1 mm.

PMID- 29338438
TI  - Challenges in adult vaccination.
AB  - Life-long primary prevention interventions beginning and continuing throughout an
      individual's lifetime are increasingly seen as key to meeting the global
      healthcare challenges that accompany demographic changes - a concept referred to
      as "Healthy aging". In this perspective, vaccination is seen as part of a triad,
      together with healthy diet and exercise. Current adult vaccine coverage is lower
      than target vaccination rates in most developed countries, and so vaccine
      preventable diseases continue to present a substantial burden on health and
      healthcare resources, especially in older individuals. In part, this is due to
      lack of knowledge and understanding of the benefits of vaccination, inconsistent
      recommendations by providers and uncertainties about cost benefits. However,
      lower vaccine effectiveness in older adults plays a part, and new vaccines with
      novel characteristics to improve effectiveness in older adults are required. A
      life-course immunization approach to ensure optimal vaccine uptake across adults
      of all ages can be expected to reduce morbidity and mortality in later life. To
      achieve this, greater emphasis on public and healthcare provider education is
      necessary, based on appropriate economic analyses that demonstrate the overall
      value of vaccination. This article introduces the technical, economic, political
      and demographic issues that make establishing effective adult vaccination
      programs such a difficult, but pressing issue, and outlines some of the steps
      that are now being taken to address them. Key messages Life-long preventive
      activities that start and continue throughout life are essential, especially as
      the world's population is "getting older". This "Healthy aging" approach includes
      not only healthy diet and physical exercise; vaccination is critical in reducing
      some infectious diseases and their complications. Many adults, especially older
      adults (who have lower immunity than younger people) develop infections such as
      influenza and shingles that could potentially be prevented through vaccination.
      This review provides a perspective on the challenges in delivering a life-course
      immunization program. While some vaccines are less effective in older people,
      newer vaccines have been developed which provide stronger and longer protection
      in older patients than standard existing vaccines. However, the benefits of
      vaccination can only be realized if the vaccines are recommended and used. For
      that purpose, greater education of patients and their healthcare providers is
      necessary. Better knowledge of vaccines and making sure that all adults are up to
      date with all their recommended vaccines is an essential part of "Healthy aging".
      This should prevent not only vaccine-preventable diseases but also reduce the
      risk of complications in later life.

PMID- 29338437
TI  - Elderly population have a decreased aneurysmal subarachnoid hemorrhage incidence
      rate than Middle aged population: a descriptive analysis of 8,144 cases in
      mainland China.
AB  - PURPOSE: Rupture of an intracranial aneurysm is a life-threatening acute
      cerebrovascular event. The purpose of this study was to investigate whether
      aneurysmal subarachnoid haemorrhage (SAH) incidence rate is higher or lower in
      elderly population than in middle aged population. MATERIALS AND METHODS:
      Aneurysmal SAH cases were collected retrospectively from the archives of 21
      hospitals in Mainland China. All the cases were collected from September 2016 and
      backward consecutively for a period of time up to 8 years. SAH was initially
      diagnosed by brain computed tomography (CT). CT angiography (CTA) or digital
      subtraction angiography (DSA) was followed and SAH was confirmed to be due to
      cerebral aneurysm rupture. For cases when multiple bleeding occurred, the age of
      the first SAH was used in this study. The total incidence from all hospitals at
      each age group were summed together for females and males respectively; then
      adjusted by the total population number at each age group for females and males
      which was from the 2010 population census of the People's Republic of China.
      RESULTS: In total there were 8,144 cases of intracranial aneurysmal SAH, with
      4,861 females and 3,283 males. For females the relative aneurysmal SAH incidence
      rate started to decrease after around 65 years old, while for males the relative
      aneurysmal SAH incidence rate started to decrease after around 53 years old.
      CONCLUSION: Our data tentatively suggest elderly patients may be at a reduced
      risk of rupture compared with patients who are younger while have similar other
      risk factors.

PMID- 29338439
TI  - Masterclass Education Program of the Clinical Coders' Society of Australia Ltd
      (CCSA).

PMID- 29338441
TI  - Across the Tasman and beyond.

PMID- 29338440
TI  - Selective progesterone receptor modulators: current applications and
      perspectives.
AB  - Selective progesterone receptor modulators (SPRMs) are steroid progesterone
      receptor ligands able to induce agonistic or antagonistic activities.
      Mifepristone, the class leader, was primarily used for pregnancy termination from
      the 1980s. Emergency contraception with extended activity was the second major
      development 30 years later, with mifepristone in some countries and ulipristal
      acetate world-wide. More recently, ulipristal acetate was released for the
      treatment of myoma-related uterine bleeding. In addition to a very rapid
      cessation of bleeding, SPRMs allow a decrease in myoma volume, as do gonadotropin
      releasing hormone analogs. However, estradiol secretion is not blunted by SPRMs.
      This offers new alternatives for myoma treatment, especially in women close to
      menopause. In conclusion, use of SPRMs has allowed significant progress in
      emergency contraception and treatment of myoma-related symptoms. Numerous future
      perspectives in women's health care are currently under evaluation.

PMID- 29338442
TI  - HIMAA Continuing Professional Development Planning Day.

PMID- 29338443
TI  - Barriers to Acupuncture Use Among Breast Cancer Survivors: A Cross-Sectional
      Analysis.
AB  - INTRODUCTION: Increasing evidence suggests that acupuncture may be helpful to
      manage common symptoms and treatment side effects among breast cancer (BC)
      survivors. Acupuncture usage among BC survivors remains low with little known
      about the barriers to its utilization. We evaluated perceived barriers to
      acupuncture use among BC survivors and explored the sociodemographic variations
      of such barriers. METHODS: We conducted a cross-sectional analysis at an urban
      academic cancer center on 593 postmenopausal women with a history of stage I-III
      hormone receptor-positive BC who were taking or had taken an aromatase inhibitor.
      We used the modified Attitudes and Beliefs about Complementary and Alternative
      Medicine instrument to evaluate patients' perceived barriers to acupuncture.
      Multiple linear regression analysis was performed to determine sociodemographic
      factors associated with perceived barrier scores. RESULTS: The most common
      barriers were lack of knowledge about acupuncture (41.6%), concern for lack of
      insurance coverage (25.0%), cost (22.3%), and difficulty finding qualified
      acupuncturists (18.6%). Compared with whites, minority patients had higher
      perceived barriers to use acupuncture (beta coefficient = 1.63, 95% confidence
      interval = 0.3-2.9, P = .013). Patients with lower education had higher barriers
      to use acupuncture (beta coefficient = 4.23, 95% confidence interval = 3.0-5.4, P
      < .001) compared with patients with college education or above. CONCLUSION: Lack
      of knowledge and concerns for insurance coverage and cost are the common barriers
      to acupuncture use among BC survivors, especially among minority patients with
      lower education. Addressing these barriers may lead to more equitable access to
      acupuncture treatment for BC survivors from diverse backgrounds.

PMID- 29338444
TI  - The First Approved Gene Therapy Product for Cancer Ad-p53 (Gendicine): 12 Years
      in the Clinic.
AB  - Gendicine (recombinant human p53 adenovirus), developed by Shenzhen SiBiono
      GeneTech Co. Ltd., was approved in 2003 by the China Food and Drug Administration
      (CFDA) as a first-in-class gene therapy product to treat head and neck cancer,
      and entered the commercial market in 2004. Gendicine is a biological therapy that
      is delivered via minimally invasive intratumoral injection, as well as by
      intracavity or intravascular infusion. The wild-type (wt) p53 protein expressed
      by Gendicine-transduced cells is a tumor suppressor that is activated by cellular
      stress, and mediates cell-cycle arrest and DNA repair, or induces apoptosis,
      senescence, and/or autophagy, depending upon cellular stress conditions. Based on
      12 years of commercial use in >30,000 patients, and >30 published clinical
      studies, Gendicine has exhibited an exemplary safety record, and when combined
      with chemotherapy and radiotherapy has demonstrated significantly higher response
      rates than for standard therapies alone. In addition to head and neck cancer,
      Gendicine has been successfully applied to treat various other cancer types and
      different stages of disease. Thirteen published studies that include long-term
      survival data showed that Gendicine combination regimens yield progression-free
      survival times that are significantly longer than standard therapies alone.
      Although the p53 gene is mutated in >50% of all human cancers, p53 mutation
      status did not significantly influence efficacy outcomes and long-term survival
      rate for Ad-p53-treated patients. To date, Shenzhen SiBiono GeneTech has
      manufactured 41 batches of Gendicine in compliance with CFDA QC/QA requirements,
      and 169,571 vials (1.0 * 1012 vector particles per vial) have been used to treat
      patients. No serious adverse events have been reported, except for vector
      associated transient fever, which occurred in 50-60% of patients and persisted
      for only a few hours. The manufacturing accomplishments and clinical experience
      with Gendicine, as well as the understanding of its cellular mechanisms of action
      and implications, could provide valuable insights for the international gene
      therapy community and add valuable data to promote further developments and
      advancements in the gene therapy field.

PMID- 29338445
TI  - Investigational inhaled therapies for non-CF bronchiectasis.
AB  - INTRODUCTION: Bronchiectasis not related to cystic fibrosis (non-CF
      bronchiectasis) are associated with a high unmet therapeutic need due to the lack
      of specifically authorized medications, especially via the inhalation route. In
      non-CF bronchiectasis chronic infection with Pseudomonas aeruginosa is common and
      favored by the persistent local inflammation and viscid sputum production.
      Therefore inhaled antibiotics, mucolytics or anti-inflammatory agents could
      represent appropriate therapeutic interventions in this setting Areas covered:
      This review herein discusses the inhaled therapies currently under investigation
      for non-CF bronchiectasis and their potential therapeutic positioning in
      exacerbation versus stable state. Expert opinion: Inhaled antipseudomonal
      antibiotics are of promising efficacy, but further efforts should also be made to
      detect bactericidal approaches against Burkholderia cepacia complex, and to
      interfere chronic inflammation topically.

PMID- 29338446
TI  - The latest animal models of ovarian cancer for novel drug discovery.
AB  - INTRODUCTION: Epithelial ovarian cancer is a heterogeneous disease classified
      into five subtypes, each with a different molecular profile. Most cases of
      ovarian cancer are diagnosed after metastasis of the primary tumor and are
      resistant to traditional platinum-based chemotherapeutics. Mouse models of
      ovarian cancer have been utilized to discern ovarian cancer tumorigenesis and the
      tumor's response to therapeutics. Areas covered: The authors provide a review of
      mouse models currently employed to understand ovarian cancer. This article
      focuses on advances in the development of orthotopic and patient-derived tumor
      xenograft (PDX) mouse models of ovarian cancer and discusses current humanized
      mouse models of ovarian cancer. Expert opinion: The authors suggest that
      humanized mouse models of ovarian cancer will provide new insight into the role
      of the human immune system in combating and augmenting ovarian cancer and aid in
      the development of novel therapeutics. Development of humanized mouse models will
      take advantage of the NSG and NSG-SGM3 strains of mice as well as new strains
      that are actively being derived.

PMID- 29338447
TI  - Changes to the ACHS Evaluation and Quality Improvement Program (EQuIP) Standards
      for Information Management.

PMID- 29338449
TI  - Operation Zipit! Privacy is a Hot Topic!

PMID- 29338448
TI  - The safety of palbociclib for the treatment of advanced breast cancer.
AB  - INTRODUCTION: Despite improvements in the diagnosis and management of early stage
      breast cancer, about one third of the patients still progress to metastatic
      disease. Most of the patients with metastatic breast cancer have a hormone
      receptor positive and human epidermal growth factor receptor 2 negative subtype
      with a median survival of more than 3 years. For these patients, endocrine
      therapy with its favorable toxicity profile is the current standard of care.
      However, patients with metastatic breast cancer have an incurable disease.
      Therefore, not only efficacy but also quality of life are key when selecting a
      therapy regimen. Areas covered: This paper aims to discuss the efficacy and
      toxicity profile of the new endocrine-based therapy option palbociclib together
      with endocrine treatment. Expert opinion: The addition of targeted agents like
      palbociclib can overcome intrinsic or acquired resistance to endocrine therapy
      and substantially prolong progression free survival. The combination of
      palbociclib plus endocrine therapy is associated with a tolerable and well
      manageable toxicity profile as well as maintenance of quality of life. Thus,
      addition of palbociclib to endocrine therapy offers a new and important treatment
      option for hormone receptor positive metastatic breast cancer.

PMID- 29338450
TI  - How can primary care physicians enhance the early diagnosis of rheumatic
      diseases?

PMID- 29338451
TI  - The Use of Clinical Classifications in the Nordic Countries.
AB  - This article gives an overview of the current use of the main clinical
      classifications in the Nordic countries. A brief introduction describes the
      background and content of Nordic co-operation in the areas of health statistics
      and health-related classifications. The use of the current international
      classifications is well established in the Nordic countries. Some Nordic
      classifications have been developed in co-operation with maintenance and updating
      performed as a joint Nordic responsibility.

PMID- 29338452
TI  - An update on diagnostic and prognostic biomarkers for traumatic brain injury.
AB  - INTRODUCTION: Traumatic brain injury (TBI) is a major worldwide neurological
      disorder of epidemic proportions. To date, there are still no FDA-approved
      therapies to treat any forms of TBI. Encouragingly, there are emerging data
      showing that biofluid-based TBI biomarker tests have the potential to diagnose
      the presence of TBI of different severities including concussion, and to predict
      outcome. Areas covered: The authors provide an update on the current knowledge of
      TBI biomarkers, including protein biomarkers for neuronal cell body injury (UCH
      L1, NSE), astroglial injury (GFAP, S100B), neuronal cell death (alphaII-spectrin
      breakdown products), axonal injury (NF proteins), white matter injury (MBP), post
      injury neurodegeneration (total Tau and phospho-Tau), post-injury autoimmune
      response (brain antigen-targeting autoantibodies), and other emerging non-protein
      biomarkers. The authors discuss biomarker evidence in TBI diagnosis, outcome
      prognosis and possible identification of post-TBI neurodegernative diseases (e.g.
      chronic traumatic encephalopathy and Alzheimer's disease), and as theranostic
      tools in pre-clinical and clinical settings. Expert commentary: A spectrum of
      biomarkers is now at or near the stage of formal clinical validation of their
      diagnostic and prognostic utilities in the management of TBI of varied severities
      including concussions. TBI biomarkers could serve as a theranostic tool in
      facilitating drug development and treatment monitoring.

PMID- 29338453
TI  - Proteomic serum biomarkers for neuromuscular diseases.
AB  - INTRODUCTION: The clinical evaluation of neuromuscular symptoms often includes
      the assessment of altered blood proteins or changed enzyme activities. However,
      the blood concentration of many muscle-derived serum markers is not specific for
      different neuromuscular disorders and also shows alterations in the course of
      these diseases. Thus, the establishment of more reliable biomarker signatures for
      improved muscle diagnostics is required. Areas covered: To address the lack of
      muscle disease-specific marker molecules, mass spectrometry-based proteomics was
      applied to the systematic identification and biochemical characterization of new
      serum biomarker candidates. This article outlines serum proteomics in relation to
      neuromuscular disorders and reviews the bioanalytical results from recent
      proteomic profiling studies of representative neuromuscular disorders, including
      motor neuron disease, muscular dystrophies and sarcopenia of old age.
      Pathophysiological changes in the skeletal muscle proteome are reflected by serum
      alterations in a variety of sarcomeric proteins, metabolic enzymes and signaling
      proteins. Expert commentary: Based on the proteomic identification of actively
      secreted or passively released skeletal muscle proteins following
      pathophysiological insults, new biomarker candidates can now be used to develop
      liquid biopsy procedures for superior diagnostic approaches, design novel
      prognostic tools and establish more reliable methods for the systematic
      evaluation of experimental therapies to treat neuromuscular disease.

PMID- 29338455
TI  - Current treatment options for meningioma.
AB  - INTRODUCTION: With an annual incidence of 5/100,000, meningioma is the most
      frequent primary tumor of the central nervous system. Risk factors are
      radiotherapy and hormone intake. Most meningiomas are grade I benign tumors, but
      up to 15% are atypical and 2% anaplastic according to the WHO 2016 histological
      criteria. Areas covered: This review details the current standard therapy based
      on international guidelines and recent literature, and describes new approaches
      developed to treat refractory cases. First-line treatments are observation and
      surgery, but adjuvant radiotherapy/radiosurgery is discussed for atypical and
      indicated for anaplastic meningiomas. The most problematic cases include skull
      base meningiomas that enclose vasculo-nervous structures and surgery- and
      radiation-refractory tumors that present with significant morbidity and
      mortality. The treatment of recurrent tumors is based on radiotherapy and
      repeated surgery. Systematic therapies are not effective in general but several
      clinical trials are ongoing. Expert commentary: Molecular characterization of the
      tumors, based on genetic mutations such as NF2, SMO, TERT, TRAF7, and on the
      methylation profile are developing, completing the histological classification
      and giving new insights into prognosis and treatment options.

PMID- 29338457
TI  - What Role Should HIMAA Take in the Continuing Professional Development (CPD) of
      Health Information Managers?

PMID- 29338454
TI  - Chemical, computational and functional insights into the chemical stability of
      the Hedgehog pathway inhibitor GANT61.
AB  - This work aims at elucidating the mechanism and kinetics of hydrolysis of GANT61,
      the first and most-widely used inhibitor of the Hedgehog (Hh) signalling pathway
      that targets Glioma-associated oncogene homologue (Gli) proteins, and at
      confirming the chemical nature of its bioactive form. GANT61 is poorly stable
      under physiological conditions and rapidly hydrolyses into an aldehyde species
      (GANT61-A), which is devoid of the biological activity against Hh signalling, and
      a diamine derivative (GANT61-D), which has shown inhibition of Gli-mediated
      transcription. Here, we combined chemical synthesis, NMR spectroscopy, analytical
      studies, molecular modelling and functional cell assays to characterise the
      GANT61 hydrolysis pathway. Our results show that GANT61-D is the bioactive form
      of GANT61 in NIH3T3 Shh-Light II cells and SuFu-/- mouse embryonic fibroblasts,
      and clarify the structural requirements for GANT61-D binding to Gli1. This study
      paves the way to the design of GANT61 derivatives with improved potency and
      chemical stability.

PMID- 29338456
TI  - An update on the safety of nutraceuticals and effects on lipid parameters.
AB  - INTRODUCTION: Cardiovascular diseases (CVDs) are the leading cause of mortality
      and disability in developed countries, whereas a large portion of patients in
      primary prevention have uncontrolled level of CVD risk factors. Dietary
      supplementation with bioactive natural compounds with demonstrated lipid-lowering
      effects is currently supported by the international guidelines for CVD prevention
      and some international expert panels. Areas covered: This review provides
      insights on issues concerning the tolerability and safety of the most commonly
      used nutraceuticals with demonstrated lipid-lowering effect in humans. They will
      be then divided into three main categories according to their mechanism of action
      (cholesterol synthesis inhibitors, intestinal cholesterol absorption inhibitors,
      and LDL-C excretion stimulants) and their pharmacological profile will be
      discussed. Expert opinion: A growing body of preclinical, epidemiological and
      clinical evidence has defined the tolerability and safety profile of the most
      commonly used lipid-lowering nutraceuticals. In the most part of cases, the side
      effects are mild and reversible. However, detailed knowledge of specific health
      risks and pharmacological interactions for each individual compound is needed for
      the management of frail patients, such as children, elderly, patients with liver
      or renal failure, and patients consuming numerous drugs.

PMID- 29338458
TI  - Tenofovir alafenamide (TAF) treatment of HBV, what are the unanswered questions?
AB  - INTRODUCTION: Tenofovir disoproxil fumarate (TDF), an ester prodrug of tenofovir
      (TFV), is one of the recommended drugs for chronic hepatitis B (CHB) patients.
      However, reduced kidney function and loss of bone mineral density have been
      reported in some CHB patients treated with TDF. Consequent to these safety
      issues, tenofovir alafenamide (TAF) [Vemlidy(r)], a phosphonate prodrug of TFV,
      was developed for the treatment of CHB patients. Areas covered: The favourable
      pharmacological profile of TAF allows a marked reduction in dosage (25 mg/day)
      thus reducing systemic exposure to tenofovir and improving the bone and renal
      safety, keeping however the same virological efficacy, compared to TDF 300
      mg/day. In two ongoing 96-week phase III trials in mainly treatment-naive HBeAg
      positive or -negative patients, TAF showed similar viral suppression but was
      associated with significantly higher alanine aminotransferase normalization rates
      and more favourable renal and bone safety compared to TDF. In a 48-week TAF
      switch study enrolling patients treated with TDF for 96 weeks, glomerular,
      tubular and bone safety parameters rapidly improved while virological suppression
      was maintained. Expert commentary: Waiting long-term large scale clinical
      practice studies aimed to confirm these advantages, TAF represents an helpful
      treatment option for both naive and TDF-exposed CHB patients.

PMID- 29338460
TI  - Research in Health Information Management.

PMID- 29338459
TI  - An interprofessional collaborative practice approach to transform heart failure
      care: An overview.
AB  - Interprofessional collaborative practice (IPCP) approaches to health care are
      increasingly recognized as necessary to achieve the Triple Aim-improved health of
      the population, improved patient care experience, and improved affordability of
      care. This paper introduces and provides an overview of an interprofessional
      intervention to improve a healthcare team, healthcare system, and patient
      outcomes for hospitalized patients with heart failure. In this paper, we describe
      the overall project resulting from a workforce training grant and the proposed
      series of future papers resulting from the interprofessional intervention.
      Collectively, these papers will describe the results of a unique IPCP approach on
      team, system, and patient outcomes as well as describe and compare organizational
      and leadership traits that affect collaborative practice. Our hope is that the
      intervention approaches, evaluation results, and lessons learned described in
      these papers will help further the efforts to spread IPCP approaches to
      transforming health care.

PMID- 29338461
TI  - mTOR dysregulation and tuberous sclerosis-related epilepsy.
AB  - INTRODUCTION: The mammalian target of rapamycin (mTOR) pathway has emerged as a
      key player for proper neural network development, and it is involved in
      epileptogenesis triggered by both genetic or acquired factors. Areas covered. The
      robust mTOR signaling deregulation observed in a large spectrum of epileptogenic
      developmental pathologies, such as focal cortical dysplasias and tuberous
      sclerosis complex (TSC), has been linked to germline and somatic mutations in
      mTOR pathway regulatory genes, increasing the spectrum of 'mTORopathies'. The
      significant advances in the field of TSC allowed for the validation of emerging
      hypotheses on the mechanisms of epileptogenesis and the identification of
      potential new targets of therapy. Recently, a double-blind phase III randomized
      clinical trial on patients with TSC related epilepsy, demonstrated that
      adjunctive treatment with mTOR inhibition is effective and safe in reducing focal
      drug resistant seizures. Expert commentary. mTOR signaling dysregulation
      represents a common pathogenic mechanism in a subset of malformations of cortical
      development, sharing histopathological and clinical features, including epilepsy,
      autism, and intellectual disability. EXIST-3 trial provided the first evaluation
      of the optimal dosage, conferring a higher chance of reducing seizure frequency
      and severity, with adverse events being similar to what observed with lower
      dosages.

PMID- 29338463
TI  - Cattanach v Melchior and Implications for Health Information Managers.

PMID- 29338462
TI  - Rethinking revascularization in patients with stable angina.
AB  - INTRODUCTION: Traditional and current perception for benefit of percutaneous
      coronary intervention (PCI) is that patients with stable angina will obtain
      symptom relief as well as improved exercise capacity after percutaneous
      revascularization. This common clinical perception is put to test in the ORBITA
      trial, the first blinded, randomized placebo-controlled clinical study ever
      conducted.Areas covered: Coronary artery disease, percutaneous coronary
      intervention, medical therapy.Expert Commentary: The authors found no significant
      improvement in exercise time, functional status, angina relief and quality of
      life in the PCI group compared with placebo. A possible explanation for this
      neutral outcome is that PCI is overvalued in symptom relief and to some extent
      explained by placebo effects or transient non-cardiac causes of chest pain.
      However, the chosen exercise tolerance improvement may have been too optimistic
      in a population with good functional capacity. Also PCI was anatomic and not
      functional driven, and follow-up duration may have been to short to wear off the
      placebo effect. While the evidence is not sufficient to alter revascularization
      guidelines, the message of this 200-patient, high-quality study is potent and
      will reverberate throughout the cardiology community and warrants further study.

PMID- 29338464
TI  - Hearing aid technology: model-based concepts and assessment.

PMID- 29338465
TI  - Standards: Flag Waving or Marking the Foundations?

PMID- 29338466
TI  - Valbenazine as the first and only approved treatment for adults with tardive
      dyskinesia.
AB  - INTRODUCTION: Valbenazine is a selective VMAT2 inhibitor that the FDA approved in
      April 2017 for the specific treatment of tardive dyskinesia (TD), a movement
      disorder commonly caused by dopamine blocking agents. Valbenazine acts to
      decrease dopamine release, reducing excessive movement found in TD. Areas
      covered: This drug profile reviews the development of valbenazine and the
      clinical trials that led to its approval as the first treatment specific to TD.
      The literature search was performed with the PubMed online database. Expert
      commentary: Two clinical trials assessing the efficacy of valbenazine have shown
      the reduction of antipsychotic-induced involuntary movement. No life threatening
      adverse effects were found. Data from a 42-week extension study demonstrated
      sustained response.

PMID- 29338467
TI  - The Pharmacy Management Information System at the Department of Veterans'
      Affairs.
AB  - This article describes the pharmacy management information systems environment
      currently being implemented at the Australian Department of Veterans' Affairs
      (DVA), and focuses on the objectives and design of the medication management
      program's management of information. As the system is new, it is too early to
      predict the difference that it will make to the operations and policy initiatives
      within the Medication Management section. The anticipated benefits are discussed.
      The user reaction, and the uses of these management data, are part of an ongoing
      benefits realisation study and the subject of a future article.

PMID- 29338468
TI  - Inhibition of the proteasome activity by graphene oxide contributes to its
      cytotoxicity.
AB  - Due to its hydrophobicity and other unique physicochemical properties, graphene
      oxide (GO) has been extensively utilized in various biological applications.
      However, introducing nanomaterials into the biological environment may raise
      serious risk in terms of nanotoxicity, leading to some unintended changes to the
      structure and the function of other biomolecules. This study investigates the
      interaction of GO with the ubiquitin-proteasome system, one of the essential
      machineries in the cellular metabolism, using a combination of experimental and
      computational approaches. The experimental results show that GO could adsorb the
      20S proteasome, causing a dose-dependent suppression of the proteolytic activity
      of proteasome. This adverse effect eventually disturbed other important cellular
      activities relevant to cell cycle and survival. Meanwhile, the molecular dynamics
      simulations revealed that when 20S proteasome was adsorbed onto the graphene
      surface, the central gate in the outer ring (alpha-subunit) for the entry and the
      exit of the peptide ligand to the protease active site was effectively blocked.
      These findings of GO induced functional disturbance of 20S proteasome provides a
      novel perspective to understand the molecular mechanism of GO's cytotoxicity,
      which might further promote applications of GO in potential therapies for various
      cancers due to the abnormal elevation of the relevant proteasome activities.

PMID- 29338469
TI  - Assessing efficacy of day 3 embryo time-lapse algorithms retrospectively: impacts
      of dataset type and confounding factors.
AB  - This study investigated the efficacy of four published day 3 embryo time-lapse
      algorithms based on different types of datasets (known implantation data [KID]
      and single embryo transfer [SET]), and the confounding effect of female age and
      conventional embryo morphology. Four algorithms were retrospectively applied to
      three types of datasets generated at Fertility North between February 2013 and
      December 2014: (a) KID dataset (n = 270), (b) a subset of SET (n = 144, end-point
      = implantation), and (c) SET (n = 144, end-point = live birth), respectively. All
      four algorithms showed progressively reduced predictive power (expressed as area
      under the receiver operating characteristics curve and 95% confidence interval
      [CI]) after application to the three datasets (a-c): Liu (0.762 [0.701-0.824] vs.
      0.724 [0.641-0.807] vs. 0.707 [0.620-0.793]), KIDScore (0.614 [0.539-0.688] vs.
      0.548 [0.451-0.645] vs. 0.536 [0.434-0.637]), Meseguer (0.585 [0.508-0.663] vs.
      0.56 [0.462-0.658] vs. 0.549 [0.445-0.652]), and Basile (0.582 [0.505-0.659] vs.
      0.519 [0.421-0.618] vs. 0.509 [0.406-0.612]). Furthermore, using KID dataset, the
      association (expressed as odds ratio and 95% CI) between time-lapse algorithms
      and implantation outcomes lost statistical significance after adjusting for
      conventional embryo morphology and female age in 3 of the 4 algorithms (KIDScore
      1.832 [1.118-3.004] vs. 1.063 [0.659-1.715], Meseguer 1.150 [1.021-1.295] vs.
      1.122 [0.981-1.284] and Basile 1.122 [1.008-1.249] vs. 1.038 [0.919-1.172]). In
      conclusion, SET is a preferred dataset to KID when developing or validating time
      lapse algorithms, and day 3 conventional embryo morphology and female age should
      be considered as confounding factors.

PMID- 29338470
TI  - Measurement error in the Liebowitz Social Anxiety Scale: results from a general
      adult population in Japan.
AB  - OBJECTIVE: Although the self-report version of Liebowitz Social Anxiety Scale
      (LSAS) is frequently used to measure social anxiety, data is lacking on the
      smallest detectable change (SDC), an important index of measurement error. We
      therefore aimed to determine the SDC of LSAS. METHODS: Japanese adults aged 20-69
      years were invited from a panel managed by a nationwide internet research agency.
      We then conducted a test-retest internet survey with a two-week interval to
      estimate the SDC at the individual (SDCind) and group (SDCgroup) levels. RESULTS:
      The analysis included 1300 participants. The SDCind and SDCgroup for the total
      fear subscale (scoring range: 0-72) were 23.52 points (32.7%) and 0.65 points
      (0.9%), respectively. The SDCind and SDCgroup for the total avoidance subscale
      (scoring range: 0-72) were 32.43 points (45.0%) and 0.90 points (1.2%),
      respectively. The SDCind and SDCgroup for the overall total score (scoring range:
      0-144) were 45.90 points (31.9%) and 1.27 points (0.9%), respectively.
      CONCLUSIONS: Measurement error is large and indicate the potential for major
      problems when attempting to use the LSAS to detect changes at the individual
      level. These results should be considered when using the LSAS as measures of
      treatment change.

PMID- 29338472
TI  - AHIMA Today.

PMID- 29338471
TI  - Transjugular intrahepatic portosystemic stent shunt placement and embolization
      for hemorrhage associated with rupture of anorectal varices.
AB  - Portal hypertension can lead to ectopic varices, which occur most frequently in
      the rectum. Rectal variceal bleeding in patients with portal hypertension is rare
      but can be life-threatening if not diagnosed and treated in a timely manner.
      However, no specific treatment guidelines have been established for rectal
      variceal bleeding. We herein report a case involving a woman with portal
      hypertension due to autoimmune liver disease who was successfully treated with a
      transjugular intrahepatic portosystemic stent shunt and variceal embolization. We
      recommend treatment of refractory ectopic variceal bleeding with a transjugular
      intrahepatic portosystemic stent shunt in combination with embolization.

PMID- 29338473
TI  - Phylogenomics of tomato chloroplasts using assembly and alignment-free method.
AB  - Phylogenetics and population genetics are central disciplines in evolutionary
      biology. Both are based on the comparison of single DNA sequences, or a
      concatenation of a number of these. However, with the advent of next-generation
      DNA sequencing technologies, the approaches that consider large genomic data sets
      are of growing importance for the elucidation of evolutionary relationships among
      species. Among these approaches, the assembly and alignment-free methods which
      allow an efficient distance computation and phylogeny reconstruction are of great
      importance. However, it is not yet clear under what quality conditions and
      abundance of genomic data such methods are able to infer phylogenies accurately.
      In the present study we assess the method originally proposed by Fan et al. for
      whole genome data, in the elucidation of Tomatoes' chloroplast phylogenetics
      using short read sequences. We find that this assembly and alignment-free method
      is capable of reproducing previous results under conditions of high coverage,
      given that low frequency k-mers (i.e. error prone data) are effectively filtered
      out. Finally, we present a complete chloroplast phylogeny for the best data
      quality candidates of the recently published 360 tomato genomes.

PMID- 29338474
TI  - Subarachnoid space diameter in chromosomally abnormal fetuses at 11-13 weeks'
      gestation.
AB  - OBJECTIVES: To examine the subarachnoid space diameters in chromosomally abnormal
      fetuses at 11-13 weeks' gestation. METHODS: Stored three-dimensional (3D)
      ultrasound volumes of the fetal head at 11-13 weeks' gestation from 407 euploid
      and 88 chromosomally abnormal fetuses (trisomy 21, n = 40; trisomy 18, n = 19;
      trisomy 13, n = 7; triploidy, n = 14; Turner syndrome, n = 8) were analyzed. The
      subarachnoid space diameters, measured in the sagittal and transverse planes of
      the fetal head, in relation to biparietal diameter (BPD) in each group of
      aneuploidies was compared to that in euploid fetuses. A total of 20 head volumes
      were randomly selected and all the measurements were recorded by two different
      observers to examine the interobserver variability in measurements. RESULTS: In
      euploid fetuses, the anteroposterior, transverse and sagittal diameters of the
      subarachnoid space increased with BPD. The median of the observed to expected
      diameters for BPD were significantly increased in triploidy and trisomy 13 but
      were not significantly altered in trisomies 21 and 18 or Turner syndrome. In
      triploidy, the subarachnoid space diameters for BPD were above the 95th centile
      of euploid fetuses in 92.9% (13 of 14) cases. The intraclass reliability or
      agreement was excellent for all three subarachnoid space diameters. CONCLUSION:
      Most fetuses with triploidy at 11-13 weeks' gestation demonstrate increased
      subarachnoid space diameters.

PMID- 29338475
TI  - Advances in atrioventricular and interventricular optimization of cardiac
      resynchronization therapy - what's the gold standard?
AB  - INTRODUCTION: Cardiac resynchronization therapy (CRT) is one of the most
      important advances in heart failure management in the last twenty years.
      Approximately one-third of patients appear not to respond to therapy. Although
      there are a number of possible mechanisms for non-response, an important factor
      is suboptimal atrioventricular (AV) and interventricular (VV) timing intervals.
      There remains controversy over whether routinely optimizing intervals is
      necessary and there is no agreed gold standard methodology. Optimization has
      classically been performed using echocardiography which has limits related to
      resource use, time-cost and variable reproducibility. Newer optimization methods
      using device-based sensors and algorithms show promise in reducing heart-failure
      hospitalization compared with echocardiography. Areas covered: This review
      outlines the rationale for optimization, the principles of AV and VV
      optimization, the standard echocardiographic approach and newer device-based
      algorithms and the evidence base for their use. Expert commentary: The
      incremental gains of optimization are likely to be real, but small, compared to
      the overall improvement gained from cardiac resynchronization itself. At this
      time routine optimization may not be mandatory but should be performed where
      there is no response to CRT. Device-based optimization algorithms appear to be
      practical and in some cases, deliver superior clinical outcomes compared to
      echocardiography.

PMID- 29338476
TI  - Evaluation and efficacy of carbon dioxide therapy (carboxytherapy) versus
      mesolipolysis in the treatment of cellulite.
AB  - BACKGROUND: Cellulite is an irregular alteration of the skin surface giving it
      cottage cheese appearance. Carboxytherapy is transcutaneous infusion of carbon
      dioxide into the affected site. Mesolipolysis aims to remove cellulite and
      improve skin texture. AIMS: To verify the efficacy and safety of carboxytherapy
      versus mesolipolysis using phosphatidylcholine (PPC) in treatment of cellulite in
      thighs area. METHODS: Forty-eight female patients with different grades of
      cellulite at thighs area were enrolled in this study. They were classified into
      two groups: group A received subcutaneous infusion of carboxytherapy, and group B
      was treated with mesolipolysis using PPC. Each group received six sessions at
      weekly intervals. sessions. The outcome measures and clinical assessment were
      based on cellulite grading scale and thigh circumference measurements.
      Standardized digital photography was taken before and after treatment. Patients
      were followed up for 6 months. RESULTS: After treatment, there was significant
      reduction in thigh circumference measurement p < 0.01 and cellulite grading scale
      p < 0.001 in both groups. The difference in cellulite grading scale and thigh
      circumference measurement in both groups was insignificant. CONCLUSIONS:
      Carboxytherapy and mesolipolysis are safe and effective in cellulite treatment.
      Carboxytherapy is a promising alternative therapeutic modality for cellulite
      treatment.

PMID- 29338477
TI  - Let the Race Begin!

PMID- 29338478
TI  - Gene-gene-environment interactions of prenatal exposed to environmental tobacco
      smoke, CYP1A1 and GSTs polymorphisms on full-term low birth weight: relationship
      of maternal passive smoking, gene polymorphisms, and FT-LBW.
AB  - OBJECTIVE: To examine the interaction effects of prenatal exposed to
      environmental tobacco smoke (ETS) and genotypes of cytochrome P4501A1 (CYP1A1),
      glutathione S-transferases (GSTs) on the risk of full-term low birth weight (FT
      LBW). STUDY DESIGN: We conducted a case-control study among pregnant women at two
      Women and Children's Hospitals in Guangdong, China (n = 910). Information was
      collected through interview, medical records review, and blood lab tests.
      Maternal selfreport and serum cotinine concentration were combined to define
      prenatal exposed to ETS. Logistic regression approach was applied for statistical
      analysis. RESULTS: Our results showed that regardless of genotypes, prenatal
      exposed to ETS significantly increased the risk of FT-LBW. Then, two-way
      interactions showed increased prevalence of FT-LBW in prenatal exposed to ETS
      mothers with the CYP1A1 variant genotype (MspI "CC"), or with GSTT1-null
      genotype. Furthermore, three-way interactions showed that women with CYP1A1
      variant (MspI "TC" or BsrDI "AG") genotypes and GSTT1 "null" genotype had higher
      risk to give birth of FT-LBW. Additionally, among nonexposed ETS mothers,
      genotype did not independently confer adverse effects on FT-LBW. CONCLUSIONS: Our
      results revealed that prenatal exposed to ETS is independently associated with FT
      LBW while gene polymorphisms of CYP1A1 and GSTs merely play modified roles in
      this process. This study extends understanding of three-way interaction, and
      stresses the need to tobacco control toward pregnant women for better pregnant
      outcomes.

PMID- 29338479
TI  - Graphene oxide regulates cox2 in human embryonic kidney 293T cells via epigenetic
      mechanisms: dynamic chromosomal interactions.
AB  - To extend the applications of engineered nanomaterials, such as graphene oxide
      (GO), it is necessary to minimize cytotoxicity. However, the mechanisms
      underlying this cytotoxicity are unclear. Dynamic chromosomal interactions have
      been used to illustrate the molecular bases of gene expression, which offers a
      more sensitive and cutting-edge technology to elucidate complex biological
      processes associated with epigenetic regulations. In this study, the role of GO
      triggered chromatin interactions in the activation of cox2, a hallmark of
      inflammation, was investigated in normal human cells. Using chromosome
      conformation capture technology, we showed that GO triggers physical interactions
      between the downstream enhancer and the cox2 promoter in human embryonic kidney
      293T (293T) via p65 and p300 complex-mediated dynamic chromatin looping, which
      was required for high cox2 expression. Moreover, tumor necrosis factor-alpha (TNF
      alpha), located upstream of the p65 signaling pathway, contributed to the
      regulation of cox2 activation through dynamic chromatin architecture. Compared
      with pristine GO and aminated GO (GO-NH2), poly (acrylic acid)-functionalized GO
      (GO-PAA) induced a weaker inflammatory response and a weaker effect on chromatin
      architecture. Our results mechanistically link GO-mediated chromatin interactions
      with the regulation of cox2 and suggest that GO derivatives may minimize toxicity
      in practical applications.

PMID- 29338480
TI  - The role of screening mammography in the era of modern breast cancer treatment.
AB  - The evidence is reviewed on the efficacy and effectiveness of mammography
      screening derived from randomized screening trials and from the surveillance of
      populations where mammography screening for breast cancer has been introduced.
      Nearly all the trials were performed in the era before modern adjuvant therapy
      for breast cancer was introduced, apart from the Canadian National Breast
      Screening Study and the UK Age trial. The former found no benefit from annual
      mammography screening for 5 years in women age 40-59 years, the latter, a non
      significant benefit from screening women by annual mammography for 7 years from
      ages 39 to 41 years. The evidence from population-based surveillance is mixed,
      most such studies having failed to consider the benefit gained from improved
      therapy. It is concluded that we have reached the point of negligible benefit
      from mammography screening for breast cancer in women at average risk, and that
      we should concentrate on early diagnosis of breast cancer and the application of
      modern therapy according to clearly defined sub-types of breast cancer.

PMID- 29338481
TI  - Statement of retraction.

PMID- 29338483
TI  - Reply to: Prehospital Intubation: Further Confounders in Trial Results.

PMID- 29338484
TI  - The association between micronucleus, nucleoplasmic bridges, and nuclear buds
      frequency and the degree of uterine cervical lesions.
AB  - BACKGROUND AND AIM: The loss of genomic stability plays an important role in
      carcinogenesis. Therefore, it is imperative to use certain biomarkers of DNA
      damage due to genomic instability in order to predict cancer risk. The aim of
      this study was the evaluation of genomic instability in patients with cervical
      lesions. MATERIALS AND METHODS: We investigated the genetic damages in 80
      subjects: 40 patients with high-grade squamous intraepithelial lesions (HSIL), 20
      patients with invasive squamous cervical cancer (SCC) and 20 healthy women with a
      biomarker in two different tissues; the micronucleus (MN) test in peripheral
      blood lymphocytes (PBL), and in buccal exfoliated cells (BEC). This study also
      examined the frequency of other nuclear anomalies such as nucleoplasmic bridges
      (NPBs) and nuclear bunds (NBUDs) in PBL. RESULTS: The frequency of MN in BEC, MN
      in PBL, NPB in PBL and NBUD in PBL were significantly higher (p < 0.001), in
      patients compared to controls. The DNA damages in BEC and PBL were correlated
      positively with histological grade of cervical lesions. CONCLUSION: Although
      larger studies are needed, our data support the predictive value of MN, NPB and
      NBUD as biomarkers of genomic instability for evaluation of risk level of cancer
      diseases.

PMID- 29338485
TI  - The Australian Coding Standards Advisory Committee.

PMID- 29338486
TI  - Rewarding effects of physical activity predict sensitivity to the acute
      subjective effects of d-amphetamine in healthy volunteers.
AB  - While individual differences in reward sensitivity are believed to generalize
      across drugs and alternative rewards, this notion has received little empirical
      attention in human research. Here, we tested whether individual differences in
      the subjective rewarding effects of physical activity were associated with the
      subjective response to d-amphetamine administration. Healthy volunteers ( n=95;
      age 18-35 years) completed questionnaires measuring the self-reported pleasurable
      effects of physical activity and other covariates, and this was followed by two
      double-blind counterbalanced sessions during which they received either 20 mg
      oral d-amphetamine or placebo. Subjective drug effects measures were collected
      before and repeatedly after drug administration. Subjective d-amphetamine-related
      effects were then reduced via principal components analysis into latent factors
      of "positive mood," "arousal," and "drug high." Multiple regression models
      controlling for placebo-related scores, session order, demographics, body mass
      index, level of physical activity, and use of other drugs showed that degree of
      self-reported physical activity reward was positively associated with d
      amphetamine-induced positive mood and arousal ( betas>=0.25, ps<=0.04), but was
      not associated with d-amphetamine-induced changes in drug high ( beta=0.13,
      p=0.24). These results provide novel evidence suggesting that individual
      differences in reward sensitivity cross over between d-amphetamine reward and
      physical activity reward in humans.

PMID- 29338488
TI  - Macrophage polarization and activation at the interface of multi-walled carbon
      nanotube-induced pulmonary inflammation and fibrosis.
AB  - Pulmonary exposure to carbon nanotubes (CNTs) induces fibrosing lesions in the
      lungs that manifest rapid-onset inflammatory and fibrotic responses, leading to
      chronic fibrosis in animals and health concerns in exposed humans. The mechanisms
      underlying CNT-induced fibrogenic effects remain undefined. Macrophages are known
      to play important roles in immune regulation and fibrosis development through
      their distinct subsets. Here we investigated macrophage polarization and
      activation in mouse lungs exposed to multi-walled CNTs (MWCNTs). Male C57BL/6J
      mice were treated with MWCNTs (XNRI MWNT-7) at 40 MUg per mouse (~1.86 mg/kg body
      weight) by oropharyngeal aspiration. The treatment stimulated prominent acute
      inflammatory and fibrotic responses. Moreover, it induced pronounced enrichment
      and polarization of macrophages with significantly increased M1 and M2
      populations in a time-dependent manner. Induction of M1 polarization was apparent
      on day 1 with a peak on day 3, but declined rapidly thereafter. On the other
      hand, the M2 polarization was induced on day 1 modestly, but was remarkably
      elevated on day 3 and maintained at a high level through day 7. M1 and M2
      macrophages were functionally activated by MWCNTs as indicated by the expression
      of their distinctive functional markers, such as iNOS and ARG1, with time courses
      parallel to M1 and M2 polarization, respectively. Molecular analysis revealed
      MWCNTs boosted specific STAT and IRF signaling pathways to regulate M1 and M2
      polarization in the lungs. These findings suggest a new mechanistic connection
      between inflammation and fibrosis induced by MWCNTs through the polarization and
      activation of macrophages during MWCNT-induced lung pathologic response.

PMID- 29338487
TI  - Acupuncture treatments for infantile colic: a systematic review and individual
      patient data meta-analysis of blinding test validated randomised controlled
      trials.
AB  - OBJECTIVE: Needle acupuncture in small children has gained some acceptance in
      Western medicine. It is controversial, as infants and toddlers are unable to
      consent to treatment. We aimed to assess its efficacy for treating infantile
      colic. DESIGN: A systematic review and a blinding-test validation based on
      individual patient data from randomised controlled trials. Primary end-points
      were crying time at mid-treatment, at the end of treatment and at a 1-month
      follow-up. A 30-min mean difference (MD) in crying time between acupuncture and
      control was predefined as a clinically important difference. Pearson's chi
      squared test and the James and Bang indices were used to test the success of
      blinding of the outcome assessors [parents]. Eligibility criteria and data
      sources: We included randomised controlled trials of acupuncture treatments of
      infantile colic. Systematic searches were conducted in Cochrane CENTRAL, MEDLINE,
      EMBASE, CINAHL and AMED, and in the Chinese language databases CNKI, VIP, Wang
      fang, SinoMed and Chinese Clinical Trial Registry. RESULTS: We included three
      randomised controlled trials with data from 307 participants. Only one of the
      included trials obtained a successful blinding of the outcome assessors in both
      the acupuncture and control groups. The MD in crying time between acupuncture
      intervention and no acupuncture control was -24.9 min [95% confidence interval,
      CI -46.2 to -3.6; three trials] at mid-treatment, -11.4 min [95% CI -31.8 to 9.0;
      three trials] at the end of treatment and -11.8 min [95% CI -62.9 to 39.2; one
      trial] at the 4-week follow-up. The corresponding standardised mean differences
      [SMDs] were -0.23 [95% CI -0.42 to -0.06], -0.10 [95% CI -0.29 to 0.08] and -0.09
      [95% CI -0.48 to 0.30]. The heterogeneity was negligible in all analyses. The
      statistically significant result at mid-treatment was lost when excluding the
      apparently unblinded study in a sensitivity analysis: MD -13.8 min [95%CI -37.5
      to 9.9] and SMD -0.13 [95%CI -0.35 to 0.09]. The registration of crying during
      treatment suggested more crying during acupuncture [odds ratio 7.7; 95% CI 2.7
      20.6; one trial]. GRADE-Moderate quality evidence. CONCLUSIONS: Percutaneous
      needle acupuncture treatments should not be recommended for infantile colic on a
      general basis. Systematic review registration: PROSPERO 2015:CRD42015023253 Key
      points The role of acupuncture in the treatment of infantile colic is
      controversial. Available trials are small and present conflicting results. There
      were no clinically important differences between infants receiving acupuncture
      and no acupuncture control in this IPD meta-analysis of randomised controlled
      trials. The data indicate that acupuncture induces some treatment pain in many of
      the children. The study results indicate that percutaneous needle acupuncture
      should not be recommended for treatment of infantile colic on a general basis.

PMID- 29338490
TI  - Treatment approaches for nasopharyngeal adenoid cystic carcinoma.

PMID- 29338489
TI  - Multimodal physiotherapy treatment based on a biobehavioral approach for patients
      with chronic cervico-craniofacial pain: a prospective case series.
AB  - The purpose of this prospective case series was to observe and describe changes
      in patients with chronic cervico-craniofacial pain of muscular origin treated
      with multimodal physiotherapy based on a biobehavioral approach. Nine patients
      diagnosed with chronic myofascial temporomandibular disorder and neck pain were
      treated with 6 sessions over the course of 2 weeks including: (1) orthopedic
      manual physiotherapy (joint mobilizations, neurodynamic mobilization, and dynamic
      soft tissue mobilizations); (2) therapeutic exercises (motor control and muscular
      endurance exercises); and (3) patient education. The outcome measures of
      craniofacial (CF-PDI) and neck disability (NDI), kinesiophobia (TSK-11) and
      catastrophizing (PCS), and range of cervical and mandibular motion (ROM) and
      posture were collected at baseline, and at 2 and 14 weeks post-baseline. Compared
      to baseline, statistically significant (p < 0.01) and clinically meaningful
      improvements that surpassed the minimal detectable change were observed at 14
      weeks in CF-PDI (mean change, 8.11 points; 95% confidence interval (CI): 2.55 to
      13.69; d = 1.38), in NDI (mean change, 5 cm; 95% CI: 1.74-8.25; d = 0.98), and in
      the TSK-11 (mean change, 6.55 cm; 95% CI: 2.79-10.32; d = 1.44). Clinically
      meaningful improvements in self-reported disability, psychological factors, ROM,
      and craniocervical posture were observed following a multimodal physiotherapy
      treatment based on a biobehavioral approach.

PMID- 29338492
TI  - Genetic variation of GRIA3 gene is associated with vulnerability to
      methamphetamine dependence and its associated psychosis.
AB  - Methamphetamine (METH) is an addictive psychostimulant drug commonly leading to
      schizophrenia-like psychotic symptoms. Disturbances in glutamatergic
      neurotransmission have been proposed as neurobiological mechanisms and the alpha
      amino-3 hydroxy-5 methyl-4 isoxazole propionic acid (AMPA) glutamate receptor has
      been implicated in these processes. Moreover, genetic variants in GRIAs, genes
      encoding AMPA receptor subunits, have been observed in association with both drug
      dependence and psychosis. We hypothesized that variation of GRIA genes may be
      associated with METH dependence and METH-induced psychosis. Genotyping of GRIA1
      rs1428920, GRIA2 rs3813296, GRIA3 rs3761554, rs502434 and rs989638 was performed
      in 102 male Thai controls and 100 METH-dependent subjects (53 with METH-dependent
      psychosis). We observed no evidence of association with METH dependence and METH
      dependent psychosis in the GRIA1 and GRIA2 polymorphisms, nor with single
      polymorphisms rs3761554 and rs989638 in GRIA3. An association of GRIA3 rs502434
      was identified with both METH dependence and METH-dependent psychosis, although
      this did not withstand correction for multiple testing. Combining the analysis of
      this site with the previously-demonstrated association with BDNF rs6265 resulted
      in a highly significant effect. These preliminary findings indicate that genetic
      variability in GRIA3 may interact with a functional BDNF polymorphism to provide
      a strong risk factor for the development of METH dependence in the Thai
      population.

PMID- 29338491
TI  - The effect of ketamine on the consolidation and extinction of contextual fear
      memory.
AB  - Ketamine, principally an antagonist of N-methyl-?-aspartate receptors, induces
      schizophrenia-like symptoms in adult humans, warranting its use in the
      investigation of psychosis-related phenotypes in animal models. Genomic studies
      further implicate N-methyl-?-aspartate receptor-mediated processes in
      schizophrenia pathology, together with more broadly-defined synaptic plasticity
      and associative learning processes. Strong pathophysiological links have been
      demonstrated between fear learning and psychiatric disorders such as
      schizophrenia. To further investigate the impact of ketamine on associative fear
      learning, we studied the effects of pre- and post-training ketamine on the
      consolidation and extinction of contextual fear memory in rats. Administration of
      25 mg/kg ketamine prior to fear conditioning did not affect consolidation when
      potentially confounding effects of state dependency were controlled for. Pre
      training ketamine (25 mg/kg) impaired the extinction of the conditioned fear
      response, which was mirrored with the use of a lower dose (8 mg/kg). Post
      training ketamine (25 mg/kg) had no effect on the consolidation or extinction of
      conditioned fear. These observations implicate processes relating to the
      extinction of contextual fear memory in the manifestation of ketamine-induced
      phenotypes, and are consistent with existing hypotheses surrounding abnormal
      associative learning in schizophrenia.

PMID- 29338493
TI  - Challenges of peroral endoscopic myotomy in the treatment of distal esophageal
      spasm.
AB  - OBJECTIVE: Distal esophageal spasm (DES) is a rare motility disorder
      characterized by premature and rapidly propagated contractions of the distal
      esophagus. Treatment options are limited and often poorly effective. Peroral
      endoscopic myotomy (POEM) seems an effective and attractive new treatment option
      for DES. In this case report we describe some of the difficulties that could
      arise. MATERIALS AND METHODS: A 84-year old man with therapy-refractory DES and
      complaints of severe dysphagia and chest pain underwent a POEM procedure under
      general anesthesia. A longer myotomy was performed to cleave the circular muscle
      layer from start till end of the spastic contractions. RESULTS: The length of the
      myotomy was 16 cm. Hyperactive spastic contractions during the procedure
      complicated the creation of the submucosal tunnel, extended the duration (134 vs.
      60-90 min for achalasia), increased postoperative pain and prolonged hospital
      admission. Intravenously nitroglycerin peroperative diminished spastic
      contractions. Postoperative a remnant of spastic contractions was present,
      proximal to the myotomy, causing persistent symptoms. CONCLUSION: Performing POEM
      for DES is challenging due to reactive hyperactive spastic contractions during
      the procedure causing technical difficulties and an extended procedure. A long
      myotomy, several centimeters above the proximal border of the spastic region, is
      essential to prevent remnants of spasticity.

PMID- 29338494
TI  - Neural correlates of response inhibition in patients with bipolar disorder during
      acute versus remitted phase.
AB  - OBJECTIVES: Elevated behavioural impulsivity has been shown to be a core feature
      of bipolar disorder. However, no study has so far investigated impulsivity
      related brain activation in patients with BD during acute versus remitted phase.
      To address the question whether elevated behavioural impulsivity and its
      differential neural pathways is a state or trait marker of BD, we employed a
      combined stop signal-go/no-go task in 30 controls, and 37 depressed and 15
      remitted patients who were retested. METHODS: Frontal brain activation was
      recorded using near-infrared spectroscopy. RESULTS: Behaviourally, we found
      increased impulsivity as indexed by higher stop signal reaction time for patients
      in their depressed phase while remitted patients did not differ from controls in
      any measure. In contrast, brain activation measurements revealed an opposite
      pattern: compared to controls, depressed patients did not show significant
      differences, while the remitted group displayed significantly decreased
      activation in bilateral prefrontal cortex during successful inhibition. Analysis
      of the remaining conditions (go, no-go, unsuccessful inhibition) did not reveal
      significant differences. CONCLUSIONS: Therefore, behavioural impulsivity and
      prefrontal hypoactivation do not seem to be a trait marker of BD. As only
      successful inhibition differentiated between groups, a specific dysfunction of
      this inhibitory process and its neural pathway may be postulated in BD.

PMID- 29338495
TI  - Clinical challenges in de novo pediatric acute myeloid leukemia.
AB  - INTRODUCTION: Although the prognosis of pediatric acute myeloid leukemia (pAML)
      has improved, with current survival rates up to 75%, relapse rates remain high.
      Areas covered: The low number of patients, the heterogeneous genomic landscape of
      AML, novel diagnostic techniques, divergent available treatment protocols, and
      dose-limiting toxicity of conventional agents all contribute to the complexity of
      AML treatment. This review gives an overview of the current clinical challenges
      with respect to diagnostics, treatment, and supportive care in pAML. Expert
      commentary: Due to intensified treatment regimens and improved supportive care
      measures, the outcome for pAML patients has improved substantially over the past
      years. However, most treatment protocols still rely on conventional
      chemotherapeutic agents with significant toxicity. Although targeted therapies
      promise to reduce the need for high doses of conventional agents with a
      subsequent decrease in toxicity, the effectiveness of these strategies remains
      unsatisfactory today. International collaborations are needed in order to address
      the ongoing therapeutic challenges of reducing toxicity while increasing
      effectivity. Consensus on risk-group classification, a common chemotherapy
      backbone and evidence-based supportive care guidelines are necessary in this
      context, at the same time enabling intergroup studies on new agents in subgroups.

PMID- 29338496
TI  - Repeated lipopolysaccharide exposure modifies immune and sickness behaviour
      response in an animal model of chronic inflammation.
AB  - Repeated lipopolysaccharide exposure is often used in longitudinal preclinical
      models of depression. However, the potential phenotypic differences from acute
      depression-mimicking effects are rarely described. This study compared chronic
      lipopolysaccharide administration of doses previously used in depression research
      to a new mode of escalating dose injections. Adult male BALB/c mice ( n=8/group)
      were injected intraperitoneally with either a single 0.83 mg/kg dose, a repeated
      0.1 mg/kg lipopolysaccharide dose or a dose which escalated weekly from 0.33 to
      0.83 mg/kg lipopolysaccharide for six weeks. The escalating lipopolysaccharide
      group demonstrated most features of sickness behaviour such as weight loss and
      reduction in food intake every week, whilst this effect was not sustained in
      other groups. Moreover, only in the escalating lipopolysaccharide group did most
      peripheral plasma cytokines levels, measured using Luminex multiplex technology,
      such as interleukin-6, tumour necrosis factor alpha and interleukin-2 remain over
      three-fold elevated on the sixth week. In addition, exposure to escalating doses
      led to a reduction of neuroblast maturation in the dentate gyrus relevant for
      depression neurobiology. Therefore, this mode of injections might be useful in
      the studies attempting to replicate neurobiological aspects of the chronic
      inflammatory state observed in mood disorders.

PMID- 29338497
TI  - A prospective observational study comparing cardiac function of small for
      gestational age with appropriate for gestational age babies using serial
      echocardiographic studies.
AB  - BACKGROUND: Approximately 30% of babies born in India are low birth weight (LBW)
      and about 70% of LBW babies are small for gestational age (SGA). Though there are
      several trials that have evaluated cardiac function of intrauterine growth
      restricted (IUGR) babies in utero, there is limited data about postnatal cardiac
      function in SGA babies during early neonatal period. This study was conducted to
      evaluate the cardiac functions of SGA babies by serial echocardiographic
      measurements and compare this with appropriate for gestational age (AGA) babies
      during the early postnatal period. MATERIAL AND METHODS: Seventy babies were
      enrolled in this prospective observational study with 35 each in the SGA and AGA
      groups. Echocardiography was performed for all babies on days 1, 2, and 3 of
      life. Myocardial performance index (MPI) was used as the primary measure to
      compare cardiac function. MPI was calculated for both ventricles using pulse wave
      Doppler and tissue Doppler. RESULTS: MPI of the left ventricle was significantly
      higher in the SGA group as compared to AGA babies during all the three
      measurement periods with SGA babies having significantly higher MPI of right
      ventricle on day 1 and day 2 but not on day 3. Left ventricular internal diameter
      index during diastole and systole (LVIDD index and LVIDS index), left atrium:
      aortic root ratio (LA:AO ratio) were significantly increased in SGA babies on all
      the occasions. Fractional shortening, ejection fraction, and area shortening were
      similar in two groups. CONCLUSIONS: Myocardial performance index of left and
      right ventricle, which evaluates both systolic and diastolic function of
      ventricles, was significantly increased in SGA babies in comparison to AGA babies
      during the first 3 days of life except MPI of the right ventricle on day 3. Thus,
      SGA babies have compromised cardiac function through all phases of the cardiac
      cycle with the performance improving spontaneously over time.

PMID- 29338498
TI  - From clinical remission to residual disease activity in spondyloarthritis and its
      potential treatment implications.
AB  - INTRODUCTION: Remission or low disease activity should be the target of therapy
      in spondyloarthritis (SpA). Due to the complexity of the disease, several
      composite indices that assess all disease domains were proposed to define a
      status of low disease activity/remission in both axial and peripheral SpA. With
      the introduction, in the past years, of effective biologic and targeted synthetic
      treatments aimed at inhibiting key cytokines and intracellular pathways, the goal
      of clinical remission has become an achievable target in these conditions.
      However, residual disease activity may occur in some domains and the management
      of patients that achieve the target of remission is still an unmet need. Areas
      covered: This manuscript aimed to review the current evidence on clinical
      remission and residual disease activity in SpA (both axial SpA and psoriatic
      arthritis), and its potential treatment implications. Expert commentary: Progress
      in our understanding of the pathogenesis of SpA will lead to a rapid increase in
      the number of available treatments, with the possibility for patients to achieve
      a status of remission. However, the topic of residual disease activity should be
      taken into consideration.

PMID- 29338499
TI  - A milestone reached?

PMID- 29338501
TI  - Does the evidence support the implementation of lung cancer screening with low
      dose computed tomography?

PMID- 29338502
TI  - The Health Information Manager as Consultant.

PMID- 29338503
TI  - The Health Information Manager in a WA Division of General Practice: A
      Multiskilled Occupation.

PMID- 29338504
TI  - The Health Information Manager as Project Manager.

PMID- 29338505
TI  - Taking on a New Role: The Health Information Manager in the Queensland Ambulance
      Service.

PMID- 29338506
TI  - The Health Information Manager in Correctional Health.

PMID- 29338507
TI  - From Private to General Practice.

PMID- 29338508
TI  - The Health Information Manager in a Division of General Practice: A Western
      Australian Experience.

PMID- 29338509
TI  - A Health Information Manager's Experience in Palliative Care.

PMID- 29338510
TI  - The Health Information Manager in Epidemiological Research: From Coder to Program
      Manager.

PMID- 29338511
TI  - Health Authority Data Management and Analysis.

PMID- 29338512
TI  - HIM in Special Health Services.

PMID- 29338513
TI  - Health Authority Data Collection.

PMID- 29338514
TI  - Portsea Safe Haven - From DRGs to Refugees.

PMID- 29338515
TI  - Feel like a Change? Read about Health Information Managers in Non-Traditional
      Jobs.

PMID- 29338516
TI  - Electronic Health Record System Risk Assessment: A Case Study from the MINET.
AB  - This article discusses the risk assessment of a health information system. A case
      study was conducted at the South Western Sydney Area Health Service to examine
      the potential risks of the Maternal and Infant Network (MINET) health information
      system using Failure Mode Effect Analysis (FMEA). FMEA was conducted by utilising
      safety attributes identified by the authors. Potential failure modes of the
      system were identified by the study. From this study, it can be concluded that
      FMEA is an appropriate risk-assessment method for MINET.

PMID- 29338517
TI  - Register-Recall Systems: Tools for Chronic Disease Management in General
      Practice.
AB  - The Divisions Diabetes and Cardiovascular Disease Quality Improvement Project
      (DDCQIP) is a national project that aims to promote quality improvement
      initiatives among Divisions of General Practice. DDCQIP has investigated the
      growth of Division-based diabetes and cardiovascular disease register-recall
      systems and the role they play in promoting evidence-based structured care within
      general practice. In the period 2000-2002, an increase in the number of GPs using
      register-recall systems and the rise in the number of active registered patients
      have made it possible to monitor quality of care and health outcome indicators,
      and contributed to the growth of a Division-based population health program.

PMID- 29338518
TI  - An 'Arresting' Kind of Job for a Health Information Manager: Working in SAPOL.

PMID- 29338519
TI  - A 'Secure' Kind of Job: The Health Information Manager in the NSW Corrections
      Health Service.

PMID- 29338520
TI  - The Role of the Health Information Manager in Forensic Mental Health.

PMID- 29338521
TI  - Best Practice for the Design of Forms.
AB  - A major objective following the 1997 amalgamation of three health services in
      Ballarat, Victoria, was the integration of the three discrete medical records
      into one system. This article describes the multidisciplinary collaboration,
      under the leadership of health information managers, that played a critical role
      in this project. Standards and best-practice evidence were used to inform new
      guidelines for forms design and development. This was complemented by another
      project to develop best-practice guidelines for producing consumer information
      with a focus on readability. Issues related to designing electronic forms were
      considered, but further work is required so that best-practice principles are
      available to guide designers. A sub-committee has been established with delegated
      authority to approve all forms. Initial evaluations have demonstrated marked
      improvements in the quality of new and revised forms.

PMID- 29338522
TI  - Health Informatics and Health Information Management in Maternal and Child Health
      Services.
AB  - In November 1997, the South Western Sydney Area Health Service launched the
      Mother and Infant Network (MINET). The key objective of MINET is to develop an
      integrated clinical data network which has the capacity to inform and support a
      continuum of care for the population of all mothers, infants and children. The
      MINET data network integrates in-patient services, ambulatory services, and
      community-based services. The focus of this article is the development and
      implementation of MINET with reference to the crucial role of data linkage and
      health informatics in health outcomes/health services research.

PMID- 29338523
TI  - Standards for Health Information and Related Health Information Technology.

PMID- 29338524
TI  - Visceral adiposity index is associated with premature ejaculation inversely: a
      cross-sectional study.
AB  - OBJECTIVE: Visceral adiposity index (VAI) is a novel indicator for the assessment
      of visceral obesity. In this study, we aimed to evaluate the relationship between
      VAI and premature ejaculation (PE). MATERIALS AND METHOD: A total of 300 men were
      included in the study. Hundred and fifty men with PE and 150 men without PE
      (control). All men were evaluated for PE by premature ejaculation diagnostic tool
      (PEDT). VAI levels were calculated using body mass index (BMI), high density
      lipoprotein and triglyceride (TG) levels. RESULTS: Mean age of the study groups
      was 34.3 +/- 5.2 (30-60) years and the mean age of the controls were 35.9 +/- 5.3
      (30-60) years. The men with PE had lower BMI, TG levels, waist circumference (WC)
      and higher high-density lipoprotein-cholesterol (HDL-C) levels. Mean VAI level
      was 4.13 +/- 0.7 in study group and 5.72 +/- 1.6 in control group, respectively.
      VAI levels were statistically higher in men without PE (p < .001). DISCUSSION:
      Our cross-sectional study demonstrated a negative correlation between VAI and PE.
      VAI is superior index for the evaluation and calculation the relationship between
      obesity and PE.

PMID- 29338527
TI  - Privacy - It's Your Issue.

PMID- 29338525
TI  - Pyocyanin induces systemic oxidative stress, inflammation and behavioral changes
      in vivo.
AB  - Pyocyanin (PCN) is a virulence factor secreted by Pseudomonas aeruginosa (P.
      aeruginosa) that has been shown to have numerous toxic effects in both in vitro
      and in vivo studies. Such toxicities include pro-inflammatory and pro-oxidant
      mediated responses. It is hypothesized that PCN can cross biological membranes
      and reach the systemic circulation, but no previous studies have investigated
      this. The aim of this study was, therefore, to quantify PCN in plasma and assess
      if systemic responses were occurring after localized intranasal administration in
      C57BL/6 J mice. This was achieved through the plasma quantification of PCN and
      assessment of changes to behavior using two commonly used tests, the forced
      swimming test and the open field test. Furthermore, evidence of systemic
      oxidative stress and inflammation was measured using malondialdehyde (MDA) and
      TNF-alpha post PCN exposure. PCN was found to cross into systemic circulation but
      in a variable manner. Furthermore, significant increases in plasma TNF-alpha and
      MDA (both p < 0.001) were observed along with changes in behavior indicative of
      systemic inflammatory responses.

PMID- 29338528
TI  - The Privacy Imperative for a Successful Health Connect.

PMID- 29338526
TI  - Associations of Abdominal Subcutaneous and Visceral Fat with Insulin Resistance
      and Secretion Differ Between Men and Women: The Netherlands Epidemiology of
      Obesity Study.
AB  - BACKGROUND: Abdominal obesity is a well-established risk factor for the
      development of type 2 diabetes. However, sex differences may exist. We aimed to
      investigate the associations of abdominal subcutaneous adipose tissue (SAT) and
      visceral adipose tissue (VAT) with insulin resistance and insulin secretion in
      men and women. METHODS: In this cross-sectional analysis of the Netherlands
      Epidemiology of Obesity study, fasting and postprandial concentrations of glucose
      and insulin were measured and abdominal fat depots were assessed using magnetic
      resonance imaging in 2253 participants (53% women). With linear regression
      analysis, we examined associations of abdominal SAT and VAT with measures of
      insulin resistance and insulin secretion in men and women, while adjusting for
      age, ethnicity, education, smoking habits, alcohol consumption, menopausal state
      and hormone use in women, and models with VAT additionally for total body fat.
      RESULTS: Participants had a mean [standard deviation (SD)] age of 56 (6) years,
      body mass index: 25.9 (3.9) kg/m2, VAT: 89 (55) cm2, and SAT: 235 (95) cm2. In
      the multivariate models in men, per SD of VAT the homeostatic model assessment of
      insulin resistance (HOMA-IR) was 20% (95% CI: 14-26) higher, and per SD SAT 21%
      (15-27) higher. In women, per SD of VAT the HOMA-IR was 40% (29-52) higher, and
      per SD SAT 12% (6-19) higher. Associations with measures of insulin secretion
      were weaker than with insulin resistance. CONCLUSIONS: In men, abdominal SAT and
      VAT were associated with insulin resistance to a similar extent, whereas in women
      particularly VAT was associated with insulin resistance and insulin secretion.
      Future studies need to unravel the mechanisms underlying the metabolic effects of
      visceral fat in women. Simple and less expensive measures that can distinct
      abdominal subcutaneous and visceral fat are needed for an improved metabolic risk
      stratification.

PMID- 29338529
TI  - Health Connect: Making Consent and Privacy a Priority.

PMID- 29338530
TI  - Clinical Coding Audits: An Annotated Bibliography.

PMID- 29338531
TI  - The Implications of Data Privacy Legislation for the Development of Hospital
      Information Systems.
AB  - This research provides an analysis of the implementation of medical data privacy
      law in Australia, with emphasis on the Victorian Health Records Act 2001 (HRA).
      We examine the ability of health organisations to respond to the requirements of
      this legislation, and similar health privacy legislation elsewhere, and
      illustrate that this ability is affected by the quality of their patient data and
      the structure and security of their databases. This article suggests that
      compliance with the legislative provisions creates implications for information
      systems development and design, which large public and private hospitals have so
      far failed to consider or act upon.

PMID- 29338532
TI  - Health Privacy: The Draft Australian National Health Privacy Code and the Shared
      Longitudinal Electronic Health Record.
AB  - An explicit distinction between shared electronic health records and those at the
      point of care is required when referring to electronic health records. The former
      raises particular privacy issues discussed in this paper in relation to Health
      Connect and the Draft Australian National Health Privacy Code. In addition to a
      number of revisions to the code, the analysis recommends that related legislation
      such as archival and freedom of information law should be reconciled as much as
      possible within the code, so that a long-term view of the uses, retention and
      preservation of the longitudinal electronic health record is balanced with
      privacy, confidentiality and public interest.

PMID- 29338533
TI  - Enhanced solubility, oral bioavailability and anti-osteoporotic effects of
      raloxifene HCl in ovariectomized rats by Igepal CO-890 nanomicelles.
AB  - The purpose of the present study was to enhance the bioavailability and anti
      osteoporotic effects of raloxifene HCl (RH) by increasing its solubility and
      inhibition of the p-glycoprotein pump using surfactant micelles of Igepal CO-890.
      The micelles were prepared by the direct method and their critical micellar
      concentration, drug dissolution rate, saturated solubility, drug loading and
      surface morphology were defined. The cytotoxicity of Igepal CO-890 and its
      ability to inhibit the p-glycoprotein pump were studied on Caco-2 cells. The
      pharmacokinetic parameters were analyzed by oral administration of a single dose
      of 15 mg/kg in Wistar rats. Anti-osteoporotic effects were studied by measuring
      the calcium, phosphorous, and uterus weight of rats after one month of oral
      administration of 6 mg/kg/day of RH in ovariectomized rats. Igepal CO-890
      micelles enhanced the RH solubility by about two-fold. The FT-IR and DSC studies
      indicated no interaction between the drug and the surfactant. XRD spectrum showed
      an amorphous state of RH in the micelles. The p-glycoprotein pump was inhibited
      by Igepal CO-890 in Caco-2 cells comparable to verapamil. Micelles increased the
      uterine weight and decreased the serum calcium and phosphorus significantly
      compared to the untreated drug. Oral bioavailability of RH increased about four
      fold by nanomicelles.

PMID- 29338534
TI  - Health Information Management Journal Reviewers 2017.

PMID- 29338535
TI  - Different lymph node staging systems for patients with adenocarcinoma of
      esophagogastric junction.
AB  - OBJECTIVE: In addition to the traditional TNM N staging system, lymph node ratio
      (LNR) and log odds of metastatic lymph nodes (LODDS) staging methods were
      developed in cancers. This study aimed to examine their relative prognostic
      performance in patients with adenocarcinoma of the esophagogastric junction
      (AEG). PATIENTS AND METHODS: Patients who underwent surgical resection for AEG
      were identified from the Surveillance, Epidemiology, and End Results (SEER)
      Program and the First Affiliated Hospital of Xi'an Jiaotong University as the
      training and validation sets, respectively. The Akaike's Information Criterion
      (AIC), Harrell's C statistic, and ROC curves were utilized for comparison.
      RESULTS: A total of 735 patients were involved in the training set. LODDS and LNR
      staging systems had better prognostic performance than the TNM N staging systems
      (when considered as a categorical variable: C index = 0.728 and 0.712 vs 0.671;
      AIC: 6247.537 and 6265.996 vs 6320.045; AUC: 0.762 and 0.719 vs 0.692. For the
      continuous model: C index = 0.675 and 0.686 vs 0.658; AIC = 6243.740 and 6261.027
      vs 6355.077; AUC = 0.778 and 0.733 vs 0.693). In the validation set of 183
      patients, the TNM N staging scheme outperformed the LODDS and LNR staging systems
      (C index = 0.788 vs 0.779 and 0.767; AIC = 1014.702 vs 1026.899 and 1025.288; AUC
      = 0.806 vs 0.787 and 0.791) when considered a categorical variable. However, when
      considered a continuous variable, the LODDS and LNR staging systems were better
      than the TNM N staging system (C index = 0.724 and 0.733 vs 0.747; AIC = 1018.075
      and 1025.803 vs 1026.085; AUC = 0.811 and 0.810 vs 0.806). CONCLUSIONS: The LNR
      and LODDS staging schemes could be considered new options for prognostic
      prediction of AEG with respect to lymph node status, especially when considered
      as continuous variables.

PMID- 29338536
TI  - P2Y12 receptor inhibitors: an evolution in drug design to prevent arterial
      thrombosis.
AB  - INTRODUCTION: P2Y12 inhibitors are a critical component of dual antiplatelet
      therapy (DAPT), which is the superior strategy to prevent arterialthrombosis in
      patients with acute coronary syndromes (ACS) and undergoing stent implantation..
      Areas covered: Basic science articles, clinical studies, and reviews from 1992
      2017 were searched using Pubmed library to collet impactful literature. After an
      introduction to the purinergic receptor biology, this review summarizes current
      knowledge on P2Y12 receptor inhibitors. Furthermore, we describe the subsequent
      improvements of next-generation P2Y12 receptor inhibitors facing the ambivalent
      problem of bleeding events versus prevention of arterial thrombosis in a variety
      of clinical settings. Therefore, we summarize data from relevant preclinical and
      clinical trials of currently approved P2Y12 receptor inhibitors (clopidogrel,
      prasugrel, ticagrelor, cangrelor) and provide strategies of drug switching and
      management of bleeding events. Expert opinion: An enormous amount of
      pharmacologic and clinical data is available for the application of P2Y12
      receptor inhibitors. Today prasugrel, ticagrelor and clopidogrel are the standard
      of care drugs during dual antiplatelet therapy for ACS patients, but have
      considerable rates of bleeding. Recent and future clinical trials will provide
      evidence for subsequent escalation and de-escalation strategies of P2Y12 receptor
      inhibition. These data may pave the way for an evidence-based, individualized
      P2Y12 receptor inhibitor therapy.

PMID- 29338537
TI  - Antidepressant prescriptions and mental health nurses: an observational study in
      Dutch general practice from 2011 to 2015.
AB  - PURPOSE: The purpose of this study was to investigate developments in
      antidepressant prescriptions by Dutch general practitioners, alongside the
      national introduction of mental health nurses. Antidepressant prescriptions are
      very common in general practice, but are often not in line with recommendations.
      The recent introduction of mental health nurses may have decreased antidepressant
      prescriptions, as general practitioners (GPs) have greater potential to offer
      psychological treatment as a first choice option instead of medication. MATERIAL
      AND METHODS: Anonymised data from the medical records of general practices
      participating in the NIVEL Primary Care Database in 2011-2015 were analysed in an
      observational study. We used multilevel logistic regression analyses to determine
      whether total antidepressant prescriptions and antidepressants prescribed within
      one week of diagnosing anxiety or depression decreased in the period 2011-2015.
      We analysed whether changes in antidepressant prescriptions were associated with
      the employment or consultation of mental health nurses. RESULTS: Antidepressants
      were prescribed in 30.3% of all anxiety or depression episodes; about half were
      prescribed within the first week. Antidepressants prescriptions for anxiety or
      depression increased slightly in the period 2011-2015. The employment of mental
      health nurses was not associated with a decreased number of prescriptions of
      antidepressants. Patients who had at least one mental health nurse consultation
      had fewer immediate prescriptions of antidepressants, but not fewer
      antidepressants in general. CONCLUSIONS: Antidepressant prescriptions are still
      common in general practice. So far, the introduction of mental health nurses has
      not decreased antidepressant prescriptions, but it may have a postponing effect.

PMID- 29338538
TI  - Increased nature relatedness and decreased authoritarian political views after
      psilocybin for treatment-resistant depression.
AB  - RATIONALE: Previous research suggests that classical psychedelic compounds can
      induce lasting changes in personality traits, attitudes and beliefs in both
      healthy subjects and patient populations. AIM: Here we sought to investigate the
      effects of psilocybin on nature relatedness and libertarian-authoritarian
      political perspective in patients with treatment-resistant depression (TRD).
      METHODS: This open-label pilot study with a mixed-model design studied the
      effects of psilocybin on measures of nature relatedness and libertarian
      authoritarian political perspective in patients with moderate to severe TRD (
      n=7) versus age-matched non-treated healthy control subjects ( n=7). Psilocybin
      was administered in two oral dosing sessions (10 mg and 25 mg) 1 week apart. Main
      outcome measures were collected 1 week and 7-12 months after the second dosing
      session. Nature relatedness and libertarian-authoritarian political perspective
      were assessed using the Nature Relatedness Scale (NR-6) and Political Perspective
      Questionnaire (PPQ-5), respectively. RESULTS: Nature relatedness significantly
      increased ( t(6)=-4.242, p=0.003) and authoritarianism significantly decreased (
      t(6)=2.120, p=0.039) for the patients 1 week after the dosing sessions. At 7-12
      months post-dosing, nature relatedness remained significantly increased ( t(5)=
      2.707, p=0.021) and authoritarianism remained decreased at trend level ( t(5)=
      1.811, p=0.065). No differences were found on either measure for the non-treated
      healthy control subjects. CONCLUSIONS: This pilot study suggests that psilocybin
      with psychological support might produce lasting changes in attitudes and
      beliefs. Although it would be premature to infer causality from this small study,
      the possibility of drug-induced changes in belief systems seems sufficiently
      intriguing and timely to deserve further investigation.

PMID- 29338539
TI  - Primary Care Provider Experience with Breast Density Legislation in
      Massachusetts.
AB  - BACKGROUND: Dense breasts on mammography independently increases breast cancer
      risk and decreases mammography sensitivity. Thirty-two states have adopted
      notification laws to raise awareness among women with dense breasts about
      supplemental screening. Little is known about these policies' impact on clinical
      practice among primary care providers (PCPs). MATERIALS AND METHODS: This study
      explores PCP attitudes, knowledge, and the impact of the Massachusetts dense
      breast notification legislation on clinical practice after its enactment in 2015.
      An anonymous, online survey at two urban safety-net hospitals was administered in
      2015-2016. Practicing MDs and nurse practitioners in primary care were invited to
      participate. RESULTS: All 145 PCPs in general internal medicine at the two sites
      were e-mailed a survey link and 80 (55%) were completed. While 64 of 80 PCPs
      surveyed (80%) had some familiarity with the legislation, none identified the 8
      required components of notifications contained in the Massachusetts legislation.
      Forty-nine percent (39/80) did not feel prepared to respond to patient questions
      about dense breasts. Forty-one percent (33/80) correctly identified that no
      current guidelines recommend the use of supplemental screening tests solely based
      on breast density and 85% (68/80) indicated interest in further training. Female
      and less experienced providers were more likely to be in favor of the legislation
      (49% vs. 11% by gender; 76% <5 years vs. 9%> 20 years). Women practitioners (55%)
      who were more likely than men (17%, p = 0.01) to agree with the policy changed
      their discussions of mammography results with patients. CONCLUSIONS: PCPs feel
      underprepared to counsel women about breast density identified on mammography and
      its implications.

PMID- 29338540
TI  - Efficacy and safety of frontline rituximab, cyclophosphamide, doxorubicin and
      prednisone plus bortezomib (VR-CAP) or vincristine (R-CHOP) in a subset of newly
      diagnosed mantle cell lymphoma patients medically eligible for transplantation in
      the randomized, phase 3 LYM-3002 study.
AB  - This post-hoc subanalysis of the LYM-3002 phase 3 study assessed the efficacy and
      safety of substituting vincristine in rituximab, cyclophosphamide, doxorubicin
      and prednisone (R-CHOP; n = 42) for bortezomib (VR-CAP; n = 38) in a subgroup of
      80 mantle cell lymphoma (MCL) patients aged <60 years who did not receive stem
      cell transplantation (SCT) despite medical eligibility. Complete response
      (CR)/unconfirmed CR (CRu) rates were 67 vs. 39% (odds ratio 3.69 [95%
      CI(confidence interval): 1.31, 10.41]; p = .012). After 40 months median follow
      up, median progression-free survival by independent radiology committee with VR
      CAP vs. R-CHOP was 32.6 vs. 12.0 months (hazard ratio (HR) 0.59 [95% CI: 0.31,
      1.13]; p = .108); median overall survival was not reached vs. 47.3 months (HR
      0.81 [95% CI: 0.33, 1.96]; p = .634). Adverse events included neutropenia
      (92/76%), thrombocytopenia (70/10%) and leukopenia (65/50%). VR-CAP represents a
      potential alternative to R-CHOP in combined and/or alternating regimens for
      younger, SCT-eligible MCL patients.

PMID- 29338541
TI  - Diagnostic Accuracy of Clinical Measures Considering Segmental Tissue Composition
      and Volume Changes of Breast Cancer-Related Lymphedema.
AB  - BACKGROUND: If we use only volumetry for measuring lymphedema, we could
      underdiagnose lymphedema with characteristics of biomechanical changes without
      definite volume change, especially in the medial forearm. METHODS AND RESULTS: In
      total, 158 breast cancer patients participated in this study. Arm volume was
      measured by water displacement volumetry, and segmental volumes were calculated
      from circumferences by using the truncated cone method. Subcutaneous ultrasound
      echogenicities were assessed on the medial side of the upper arm and forearm of
      both arms and graded by subcutaneous echogenicity grade (SEG) and revised SEG
      (rSEG). The standards for diagnosing secondary lymphedema were according to the
      volume change and clinical stage. Sensitivity, specificity, receiver-operating
      characteristic (ROC) curve, and area under the curve (AUC) were used. Analysis of
      ROC curves yielded AUCs of 0.875-0.933 (p < 0.001). Volume differences in each
      segment were significantly different among the grades by SEG. The highest AUC was
      found for volume difference (AUC = 0.919, 95% confidence interval [CI] = 0.860
      0.978) in the upper arm near the elbow; however, in the medial forearm, the
      highest AUC was found for rSEG (AUC = 0.948, 95% CI = 0.923-0.965 in the proximal
      forearm; AUC = 0.940, 95% CI = 0.923-0.965 in the distal forearm). CONCLUSIONS:
      Our findings support the use of SEG by ultrasound in the assessment of
      lymphedema, especially in the medial region of the forearm. Subcutaneous
      ultrasound echogenicities may improve the accuracy of diagnosis of lymphedema in
      the forearm.

PMID- 29338542
TI  - The novel microtubule-associated CAP-glycine protein Cgp1 governs growth,
      differentiation, and virulence of Cryptococcus neoformans.
AB  - Microtubules are involved in mechanical support, cytoplasmic organization, and
      several cellular processes by interacting with diverse microtubule-associated
      proteins such as plus-end tracking proteins, motor proteins, and tubulin-folding
      cofactors. A number of the cytoskeleton-associated proteins (CAPs) contain the
      CAP-glycine-rich (CAP-Gly) domain, which is evolutionarily conserved and
      generally considered to bind to alpha-tubulin to regulate the function of
      microtubules. However, there has been a dearth of research on CAP-Gly proteins in
      fungal pathogens, including Cryptococcus neoformans, which is a global cause of
      fatal meningoencephalitis in immunocompromised patients. In this study, we
      identified five CAP-Gly protein-encoding genes in C. neoformans. Among these,
      Cgp1 encoded by CNAG_06352 has a unique domain structure containing CAP-Gly,
      SPEC, and Spc7 domains that is not orthologous to CAPs in other eukaryotes.
      Supporting the role of Cgp1 in microtubule-related function, we demonstrate that
      deletion or overexpression of CGP1 alters cellular susceptibility to
      thiabendazole, a microtubule destabilizer and that Cgp1 is co-localized with
      cytoplasmic microtubules. Related to the cellular function of microtubules, Cgp1
      governs the maintenance of membrane stability and genotoxic stress responses.
      Deletion of CGP1 also reduces production of melanin pigment and attenuates the
      virulence of C. neoformans. Furthermore, we demonstrate that Cgp1 uniquely
      regulates the sexual differentiation of C. neoformans with distinct roles in the
      early and late stage of mating. Domain analysis revealed that the CAP-Gly domain
      plays a major role in all Cgp1 functions examined. In conclusion, this novel CAP
      Gly protein, Cgp1, has pleotropic roles in regulating growth, stress responses,
      differentiation, and virulence in C. neoformans.

PMID- 29338544
TI  - A Direct Comparison between Norepinephrine and Phenylephrine for Augmenting
      Spinal Cord Perfusion in a Porcine Model of Spinal Cord Injury.
AB  - Current clinical guidelines recommend elevating the mean arterial blood pressure
      (MAP) to increase spinal cord perfusion in patients with acute spinal cord injury
      (SCI). This is typically achieved with vasopressors such as norepinephrine (NE)
      and phenylephrine (PE). These drugs differ in their pharmacological properties
      and potentially have different effects on spinal cord blood flow (SCBF),
      oxygenation (PO2), and downstream metabolism after injury. Using a porcine model
      of thoracic SCI, we evaluated how these vasopressors influenced intraparenchymal
      SCBF, PO2, hydrostatic pressure, and metabolism within the spinal cord adjacent
      to the injury site. Yorkshire pigs underwent a contusion/compression SCI at T10
      and were randomized to receive either NE or PE for MAP elevation of 20 mm Hg, or
      no MAP augmentation. Prior to injury, a combined SCBF/PO2 sensor, a pressure
      sensor, and a microdialysis probe were inserted into the spinal cord adjacent to
      T10 at two locations: a "proximal" site and a "distal" site, 2 mm and 22 mm from
      the SCI, respectively. At the proximal site, NE and PE resulted in little
      improvement in SCBF during cord compression. Following decompression, NE resulted
      in increased SCBF and PO2, whereas decreased levels were observed for PE.
      However, both NE and PE were associated with a gradual decrease in the lactate to
      pyruvate (L/P) ratio after decompression. PE was associated with greater
      hemorrhage through the injury site than that in control animals. Combined, our
      results suggest that NE promotes better restoration of blood flow and oxygenation
      than PE in the traumatically injured spinal cord, thus providing a physiological
      rationale for selecting NE over PE in the hemodynamic management of acute SCI.

PMID- 29338543
TI  - Lucidone suppresses dengue viral replication through the induction of heme
      oxygenase-1.
AB  - Dengue virus (DENV) infection causes life-threatening diseases such as dengue
      hemorrhagic fever and dengue shock syndrome. Currently, there is no effective
      therapeutic agent or vaccine against DENV infection; hence, there is an urgent
      need to discover anti-DENV agents. The potential therapeutic efficacy of lucidone
      was first evaluated in vivo using a DENV-infected Institute of Cancer Research
      (ICR) suckling mouse model by monitoring body weight, clinical score, survival
      rate, and viral titer. We found that lucidone effectively protected mice from
      DENV infection by sustaining survival rate and reducing viral titers in DENV
      infected ICR suckling mice. Then, the anti-DENV activity of lucidone was
      confirmed by western blotting and quantitative-reverse-transcription-polymerase
      chain reaction analysis, with an EC50 value of 25 +/- 3 MUM. Lucidone
      significantly induced heme oxygenase-1 (HO-1) production against DENV replication
      by inhibiting DENV NS2B/3 protease activity to induce the DENV-suppressed
      antiviral interferon response. The inhibitory effect of lucidone on DENV
      replication was attenuated by silencing of HO-1 gene expression or blocking HO-1
      activity. In addition, lucidone-stimulated nuclear factor erythroid 2-related
      factor 2 (Nrf2), which is involved in transactivation of HO-1 expression for its
      anti-DENV activity. Taken together, the mechanistic investigations revealed that
      lucidone exhibits significant anti-DENV activity in in vivo and in vitro by
      inducing Nrf2-mediated HO-1 expression, leading to blockage of viral protease
      activity to induce the anti-viral interferon (IFN) response. These results
      suggest that lucidone is a promising candidate for drug development.

PMID- 29338545
TI  - Identification of G2/M phase transition by sequential nuclear and cytoplasmic
      changes and molecular markers in mice intestinal epithelial cells.
AB  - Although the regulatory network of G2/M phase transition has been intensively
      studied in mammalian cell lines, the identification of morphological and
      molecular markers to identify G2/M phase transition in vivo remains elusive. In
      this study, we found no obvious morphological changes between the S phase and G2
      phase in mice intestinal epithelial cells. The G2 phase could be identified by
      Brdu incorporation resistance, marginal and scattered foci of histone H3
      phosphorylated at Ser10 (pHH3), and relatively intact Golgi ribbon. Prophase
      starts with nuclear transformation in situ, which was identified by a series of
      prophase markers including nuclear translocation of cyclinB1, fragmentation of
      the Golgi complex, and a significant increase in pHH3. The nucleus started to
      move upwards in the late prophase and finally rounded up at the apical surface.
      Then, metaphase was initiated as the level of pHH3 peaked. During anaphase and
      telophase, pHH3 sharply decreased, while Ki67 was obviously bound to chromosomes,
      and PCNA was distributed throughout the whole cell. Based on the aforementioned
      markers and Brdu pulse labeling, it was estimated to take about one hour for most
      crypt cells to go through the G2 phase and about two hours to go through the G2-M
      phase. It took much longer for crypt base columnar (CBC) stem cells to undergo G2
      prophase than rapid transit amplifying cells. In summary, a series of
      sequentially presenting markers could be used to indicate the progress of G2/M
      events in intestinal epithelial cells and other epithelial systems in vivo.

PMID- 29338546
TI  - Estimation of the volume under the receiver-operating characteristic surface
      adjusting for non-ignorable verification bias.
AB  - The receiver-operating characteristic surface is frequently used for presenting
      the accuracy of a diagnostic test for three-category classification problems. One
      common problem that can complicate the estimation of the volume under receiver
      operating characteristic surface is that not all subjects receive the
      verification of the true disease status. Estimation based only on data from
      subjects with verified disease status may be biased, which is referred to as
      verification bias. In this article, we propose new verification bias correction
      methods to estimate the volume under receiver-operating characteristic surface
      for a continuous diagnostic test. We assume the verification process is missing
      not at random, which means the missingness might be related to unobserved
      clinical characteristics. Three classes of estimators are proposed, namely,
      inverse probability weighted, imputation-based, and doubly robust estimators. A
      jackknife estimator of variance is derived for all the proposed volume under
      receiver-operating characteristic surface estimators. The finite sample
      properties of the new estimators are examined via simulation studies. We
      illustrate our methods with data collected from Alzheimer's disease research.

PMID- 29338548
TI  - Glycine transporter-1 inhibitors: a patent review (2011-2016).
AB  - INTRODUCTION: Numerous research groups have developed GlyT-1 inhibitors in the
      pursuit of providing a novel antipsychotic treatment for schizophrenia. Despite
      multiple compounds advancing into clinical trials, a GlyT-1 inhibitor has yet to
      emerge to treat patients. However, the approach remains heavily investigated as
      it presents potential therapeutic utility for several other CNS and non-CNS
      related indications. Areas covered: This review discusses various GlyT-1
      inhibitor chemotypes identified and provides an overview of patent applications
      filed and published during the period of 2011-2016. The review largely focuses on
      composition of matter patent applications, although two recently disclosed method
      of use patents are discussed. Clinical reports are also disseminated. Expert
      opinion: Mounting clinical failures with schizophrenic patients have blunted
      enthusiasm for GlyT-1 inhibition as an approach to treat the disease. However,
      research in the area remains quite active, as therapeutic potential for several
      additional indications has emerged. There are numerous and diverse GlyT-1
      chemotypes now available that exhibit differentiating modes of binding and ligand
      target binding kinetics, and this rich diversity of chemical matter may help
      further elucidate the target's pharmacological role in various indications and
      lead to the identification of a compound with optimal properties that may someday
      become a drug.

PMID- 29338549
TI  - Sedation in cardiac arrhythmias management.
AB  - INTRODUCTION: Procedural sedation is of paramount importance for a plethora of
      electrophysiological procedures. From electrical cardioversion to
      electrophysiology studies, device implantations, and catheter ablations,
      intraprocedural sedation and anesthesia have a pivotal role in allowing
      procedural success while ensuring patient safety and avoiding discomfort. Areas
      covered: The present review will discuss the current state-of-the-art in sedation
      and anesthesia during electrical cardioversion, cardiac implantable electronic
      device implantation, catheter ablation and electrophysiology studies. Specific
      information will be provided for each procedure in order to reach the core of
      this important clinical issue, and specific protocols will be compared. The main
      pro-arrhythmic and anti-arrhythmic effects of the most commonly used sedatives
      will also be discussed. Expert commentary: According to much recent evidence, the
      cardiologist can be the only person responsible for sedation administration in
      many settings, highlighting few safety issues associated with the absence of a
      dedicated anesthesiologist thus a concomitant reduction in costs. However, many
      concerns have been raised in allowing non-anesthesiologists to manage sedatives,
      as adverse events, while rare, could have catastrophic consequences. The present
      paper will highlight when a cardiologist-directed sedation is considered safe,
      how it should be performed, and the pros and cons related to this strategy.

PMID- 29338547
TI  - Neuroimaging meta-analysis of cannabis use studies reveals convergent functional
      alterations in brain regions supporting cognitive control and reward processing.
AB  - Lagging behind rapid changes to state laws, societal views, and medical practice
      is the scientific investigation of cannabis's impact on the human brain. While
      several brain imaging studies have contributed important insight into
      neurobiological alterations linked with cannabis use, our understanding remains
      limited. Here, we sought to delineate those brain regions that consistently
      demonstrate functional alterations among cannabis users versus non-users across
      neuroimaging studies using the activation likelihood estimation meta-analysis
      framework. In ancillary analyses, we characterized task-related brain networks
      that co-activate with cannabis-affected regions using data archived in a large
      neuroimaging repository, and then determined which psychological processes may be
      disrupted via functional decoding techniques. When considering convergent
      alterations among users, decreased activation was observed in the anterior
      cingulate cortex, which co-activated with frontal, parietal, and limbic areas and
      was linked with cognitive control processes. Similarly, decreased activation was
      observed in the dorsolateral prefrontal cortex, which co-activated with frontal
      and occipital areas and linked with attention-related processes. Conversely,
      increased activation among users was observed in the striatum, which co-activated
      with frontal, parietal, and other limbic areas and linked with reward processing.
      These meta-analytic outcomes indicate that cannabis use is linked with
      differential, region-specific effects across the brain.

PMID- 29338550
TI  - The role of tumor angiogenesis as a therapeutic target in colorectal cancer.
AB  - INTRODUCTION: Angiogenesis is a complex process regulated by several pro- and
      anti-angiogenic factors, thus the loss of its fine equilibrium plays a key role
      in colorectal cancer (CRC) development and progression. Therapeutic agents
      targeting VEGF/VEGFR signaling, the main regulator of this process, proved to be
      effective across different treatment lines in metastatic CRC (mCRC) and
      contributed greatly to improve patients' survival in recent years. Areas covered:
      This review aimed to summarize the actual body of knowledge available on the VEGF
      pathway in CRC, including currently available anti-angiogenic drugs and treatment
      challenges, mechanisms of resistance, promising predictive biomarkers and future
      perspectives. Expert commentary: Angiogenesis inhibition in subsequent lines of
      treatment is a valid strategy in the continuum of care of mCRC patients. In this
      scenario, the availability of multiple agents warrants to tailor therapy to an
      individualized approach. However, the validation of predictive biomarkers to aid
      therapeutic decisions remains an issue. Intrinsic and adaptive resistance to anti
      angiogenic agents comprises distinct and intertwined processes, eventually
      leading to treatment failure and disease progression. The expanding knowledge on
      the mechanisms underlying the angiogenesis pathway, different potential treatment
      targets and mechanisms of tumor resistance, may lead to promising new
      perspectives in this field.

PMID- 29338551
TI  - The regulatory roles of B cell subsets in transplantation.
AB  - INTRODUCTION: B cells mediate allograft rejection through antigen presentation,
      and production of cytokines and antibodies. More and more immunosuppressive
      agents specifically targeting B cells and plasma cells have been applied in
      clinical transplantation. However, recent studies have indicated the regulatory
      roles of B cells. Therefore, it is vital to clarify the different effects of B
      cell subsets in organ transplantation so that we can completely understand the
      diverse functions of B cells in transplantation. Areas covered: This review
      focuses on the regulatory roles of B cells in transplantation. B cell subsets
      with immune modulation and factors mediating immunosuppressive functions of
      regulatory B (Breg) cells were analyzed. Therapies targeting B cells and the
      application of B cells for transplant tolerance induction were discussed. Expert
      commentary: Besides involving rejection, B cells could also play regulatory roles
      in transplantation. Breg cells and the related markers may be used to predict the
      immune tolerant state in transplant recipients. New therapeutic strategies
      targeting B cells should be explored to promote tolerance induction with less
      impact on the host's protective immunity in organ transplanted patients.

PMID- 29338552
TI  - The Adverse Drug Reactions Reporting Project.

PMID- 29338553
TI  - Comprehensive Clinicopathologic and Updated Immunohistochemical Characterization
      of Primary Ovarian Mucinous Carcinoma.
AB  - The distinction of primary mucinous ovarian carcinoma (PMOC) from other primaries
      or secondaries is essential for selecting therapeutic options and
      prognostication. We aimed to characterize the immunohistochemical profile of 36
      PMOCs using an extended immunohistochemical panel, with clinicopathologic
      features and outcome. PAX8 was negative in 30 (83.3%), and SATB2 was negative in
      32/35. HNF1B, AMACR, and napsin-A were detected in 33 (91.7%), 35 (97.2%), and 0
      (0%), respectively. MMR proteins and ARID1A were retained in 100%; PTEN was lost
      in 4 (11.1%). P53 was aberrant in 10 (27.8%); none overexpressed p16. HER2 was
      positive in 6/35 (17.1%). Most PMOCs had a favorable outcome. However, recurrence
      is usually fatal. The typical tumor profile was CK7+, CK20+/-, CDX2+/-, PAX8-, ER
      , PgR-, and SATB2-. HER2 positivity suggests a possible target for therapy in
      advanced disease.

PMID- 29338554
TI  - Site Specific Evaluation of Lymphatic Vessel Sclerosis in Lower Limb Lymphedema
      Patients.
AB  - BACKGROUND: Histological changes in the collecting lymphatics in patients with
      lymphedema are classified as Normal type, Ectasis type, Contraction type, and
      Sclerosis type (NECST) classification. In this study, we investigated the
      condition of the lymphatic vessels in different sites of the legs. PATIENTS AND
      METHODS: We prospectively investigated the lymphatic vessels of patients with
      lymphedema who underwent lymphaticovenous anastomosis (LVA) from August 8, 2014
      to August 4, 2015 based on the NECST classification. Lymphedema was diagnosed
      using lymphoscintigraphy, indocyanine green (ICG) lymphography, and the
      International Society of Lymphology (ISL) Classification. The affected limbs were
      divided into four sites: proximal thigh (Site 1), distal thigh (Site 2), proximal
      crus (Site 3), and distal crus (Site 4). RESULTS: A total of 109 patients (205
      limbs and 1028 lymphatics) were included in this study. Of the 109 patients,
      there were 100 women and 9 men with an average age of 61 years. The ratio of
      Ectasis type vessels increased toward the distal end of the limb with the highest
      occurrence rate being 54% at Site 4. As ISL stage, ICG stage, and
      lymphoscintigraphy stage advanced, so too did the ratio of Sclerosis type. In
      secondary lymphedema patients with lymphedema, the ratio of Ectasis type was more
      predominant in the distal end of the limb, whereas this tendency was not observed
      in primary lymphedema patients. CONCLUSIONS: Sclerotic lymphatics are more
      predominantly found in the proximal limb whereas nonsclerotic vessels are more
      often found toward the distal end. These findings help lymphatic surgeon
      determine incision sites.

PMID- 29338555
TI  - Positive Neighborhood Norms Buffer Ethnic Diversity Effects on Neighborhood
      Dissatisfaction, Perceived Neighborhood Disadvantage, and Moving Intentions.
AB  - Positive neighborhood norms, such as strong local networks, are critical to
      people's satisfaction with, perceived disadvantage of, and intentions to stay in
      their neighborhood. At the same time, local ethnic diversity is said to be
      detrimental for these community outcomes. Integrating both frameworks, we tested
      whether the negative consequences of diversity occur even when perceived social
      norms are positive. Study 1 ( N = 1,760 German adults) showed that perceptions of
      positive neighborhood norms buffered against the effects of perceived diversity
      on moving intentions via neighborhood satisfaction and perceived neighborhood
      disadvantage. Study 2 ( N = 993 Dutch adults) replicated and extended this
      moderated mediation model using other characteristics of diversity (i.e.,
      objective and estimated minority proportions). Multilevel analyses again revealed
      consistent buffering effects of positive neighborhood norms. Our findings are
      discussed in light of the ongoing public and political debate concerning
      diversity and social and communal life.

PMID- 29338556
TI  - Hong Kong Liberals Are WEIRD: Analytic Thought Increases Support for Liberal
      Policies.
AB  - This study tests whether liberals and conservatives within the same society think
      as if they were from different cultures. I tested this by measuring the cultural
      thought style of social liberals and conservatives in Hong Kong (Study 1).
      Liberals tended to think more analytically (more "WEIRD"), and conservatives
      tended to think more holistically (more common in East Asia). In Study 2, I
      trained people to think analytically or holistically before they read articles on
      political issues. Analytic thought caused people to form more liberal opinions,
      and holistic thought caused people to form more conservative opinions. The
      thought training affected participants' responses to a social issue, but not an
      economic issue or whether they identified as liberal or conservative. This study
      replicates a previous U.S. finding in an East Asian culture and a different
      political environment, suggesting that the link between politics and thought
      style extends beyond the United States.

PMID- 29338557
TI  - Biosynthesis, characterization and leishmanicidal activity of a biocomposite
      containing AgNPs-PVP-glucantime.
AB  - AIM: Development of functionalized nanocomposites containing AgNPs-PVP
      Glucantime(r) to evaluate their leishmanicidal activity as a novel method for
      improving the pharmacological properties of the drug Glucantime(r) against
      extracellular promastigotes and intracellular amastigotes of Leishmania
      amazonensis in vitro to treat cutaneous leishmaniasis. MATERIALS & METHODS: The
      silver nanoparticles and nanocomposites prepared containing silver nanoparticles,
      polyvinylpyrrolidone and different amounts of Glucantime were characterized using
      transmission electron microscopy, x-ray diffraction, energy-dispersive x-ray
      spectroscopy and zeta potential analysis; in addition, the in vitro cytotoxicity
      was evaluated. RESULTS: The nanocomposites showed an inhibitory effect on the
      cellular viability of promastigote forms, with values of 47.06, 51.71 and 65.67%
      for nanocomposite1, nanocomposite2 and nanocomposite3, respectively, as well as a
      dose-dependent decrease in the infectivity index, with values of 33.33 and 23%
      for nanocomposite2 and nanocomposite3, respectively. CONCLUSION: The proposed
      nanocomposite reveals leishmanial activity and the absence of cytotoxicity in
      macrophages. Further investigations will be conducted in vivo.

PMID- 29338558
TI  - The Influence of Masculine Norms and Occupational Factors on Mental Health:
      Evidence From the Baseline of the Australian Longitudinal Study on Male Health.
AB  - Men employed in male-dominated occupations are at elevated risk of work-related
      fatalities, injuries, and suicide. Prior research has focused on associations
      between psychosocial and physical exposures at work and health outcomes. However,
      masculine norms may also contribute to mental health. We used data from the
      baseline survey of the Australian Longitudinal Study on Male Health to examine
      whether: (a) men in male-dominated jobs report greater adherence to masculine
      norms; (b) being in a male-dominated occupation is associated with poorer mental
      health; and (c) being in a male-dominated occupation modifies the association
      between masculine norms and mental health. Masculine norms were measured using
      the Conformity to Masculine Norms Inventory (CMNI-22). Mental health was assessed
      using the SF-12. Results of regression analysis (adjusted for covariates) suggest
      a linear relationship between the extent to which an occupation is male-dominated
      and endorsement of values on the CMNI-22. Many CMNI-22 subscales were related to
      poorer mental health. However, the need for self-reliance was identified as the
      strongest predictor of poorer mental health. The mental health scale did not
      appear to be patterned by occupational gender composition and we did not find an
      interaction between the gender ratio of an occupation and the CNMI-22 scale.
      These findings highlight the need to address harmful aspects of masculinity as a
      potential cause of mental health problems. More longitudinal research is needed
      on the social domains in which gender and health are experienced, such as in the
      workplace.

PMID- 29338559
TI  - How can 3D printing be a powerful tool in nanomedicine?

PMID- 29338560
TI  - Scientists, Instruments, and Even Brains in Transfer: German-Spanish Postwar
      Networks and the Construction of the Neuroendocrine System (1952-1960).
AB  - This article presents the process of relocation of hegemonies and "center
      periphery" dynamics in neuroanatomy after World War II through the study of the
      links between the Spanish anatomical school of Jose Escolar Garcia and some
      German institutions. We have analyzed their works on the morphology of the
      neuroendocrine system as a case study, showing how the first contacts of the
      Spaniards with the United States started a material transfer process between
      centers on both sides of the Atlantic Ocean through the mediation-and adaptation
      of the periphery. The case also shows how scientific networks in the "new" Europe
      were reestablished after the Nazi era and how important these systems were for
      the transfer of knowledge, using them for the circulation of experts,
      instruments, and even biological samples.

PMID- 29338561
TI  - Menopause and cardiovascular disease.
AB  - Cardiovascular disease is very common in women. It is still under diagnosed and
      under treated. Many women are not having their risk factors for cardiovascular
      disease properly addressed. Many healthcare professionals are uncertain about the
      role of hormones in cardiovascular disease. This article gives an overview of the
      most important risk factors for cardiovascular disease and how to manage those
      risk factors appropriately, based on the available evidence.

PMID- 29338562
TI  - Targeted microbubbles with ultrasound irradiation and PD-1 inhibitor to increase
      antitumor activity in B-cell lymphoma.
AB  - AIM: Severe cardiac toxicity of doxorubicin and an immunosuppressive tumor micro
      environment become main obstacles for the effective treatment of B-cell lymphoma.
      In this research, rituximab-conjugated and doxorubicin-loaded microbubbles (RDMs)
      were designed for exploring a combination approach of targeted microbubbles with
      ultrasound (US) irradiation and PD-1 inhibitor to overcome obstacles mentioned
      above. METHODS: In vivo studies were performed on SU-DHL-4 cell-grafted mice and
      ex vivo studies were performed on CD20+ human SU-DHL-4 cells and human T cells.
      RESULTS: A greater therapeutic effect and higher expression of PD-L1 protein
      expression were obtained with RDMs with US irradiation in vivo. A significant
      inhibitory effect on SU-DHL-4 B-cell lymphoma cells was observed after treated by
      RDMs with US irradiation and PD-1 inhibitor ex vivo. CONCLUSION: Combination of
      RDMs with US irradiation and PD-1 inhibitor could be a promising therapeutic
      strategy for B-cell lymphoma.

PMID- 29338564
TI  - 1986, The Michael Faraday prize and the promotion of science in the nineteenth
      century.

PMID- 29338563
TI  - The Long-Term Effects of the Youth Crime Prevention Program "New Perspectives" on
      Delinquency and Recidivism.
AB  - New Perspectives (NP) aims to prevent persistent criminal behavior. We examined
      the long-term effectiveness of NP and whether the effects were moderated by
      demographic and delinquency factors. At-risk youth aged 12 to 19 years were
      randomly assigned to the intervention group (NP, n = 47) or care as usual (CAU, n
      = 54). Official and self-report data were collected to assess recidivism. NP was
      not more effective in reducing delinquency levels and recidivism than CAU. Also,
      no moderator effects were found. The overall null effects are discussed,
      including further research and policy implications.

PMID- 29338565
TI  - Associations of the lipid genetic variants Thr54 ( FABP2) and -493T ( MTTP) with
      total cholesterol and low-density lipoprotein cholesterol levels in Mexican
      subjects.
AB  - Objective Mexico has one of the world's highest rates of obesity, which is
      influenced by lipid-genetic and lifestyle factors. This study aimed to determine
      whether FABP2 (Ala54Thr) and MTTP (-493 G/T) genetic polymorphisms are associated
      with metabolic disorders in Mexican subjects. Methods A total of 523 subjects
      participated in a cross-sectional study. Genotyping for FABP2 and MTTP was
      performed using real-time RT-PCR. Biochemical and anthropometric data were
      evaluated. Results The genetically at-risk group (Thr54/-493T) was associated
      with significantly higher total and low-density lipoprotein cholesterol levels
      (difference between genetically at-risk group and wild-type group: 10.6 mg/dL and
      8.94 mg/dL, respectively). Carriers within the genetically at-risk group had a
      significantly higher prevalence rate of hypercholesterolaemia (42.5% vs. 32.0%)
      and higher LDL-C levels (37.6% vs. 26.4%) than did non-carriers. Conclusions
      Subjects who are genetically at risk (Thr54/-493T) have higher total cholesterol
      levels, low-density lipoprotein cholesterol levels, and prevalence rate of
      hypercholesterolaemia. These findings highlight the importance of basing
      nutritional intervention strategies for preventing and treating chronic diseases
      on individual genetic characteristics.

PMID- 29338566
TI  - Constructing heparin-modified pancreatic decellularized scaffold to improve its
      re-endothelialization.
AB  - Pancreas transplantation is considered as a promising therapeutic option with the
      potential to cure diabetes. However, efficacy of current clinical transplantation
      is limited by the donor organ. With regard to creating a functional pancreas
      tissue equivalent for transplantation, vascularization remains a large obstacle.
      To enhance the angiogenic properties of pancreatic decellularized scaffold,
      surface modification of the vasculature was used to promote endothelialization
      efficiency. In this study, an endothelialized pancreatic decellularized scaffold
      was obtained through heparin modification under mild conditions. The
      immobilization of heparin was performed through 1-ethyl-3-(3-dimethylaminopropyl)
      carbodiimide and N-Hydroxysuccinimide. The morphology, ultra-structure and
      porosity of the heparinized scaffold were characterized by toluidine blue
      staining, scanning electron microscope and infrared spectrum. The adhesion,
      proliferation and angiogenesis of human umbilical vein endothelial cells on
      heparin-pancreatic decellularized scaffold were also researched in vitro. In vivo
      transplantation was also performed to observe the location of human umbilical
      vein endothelial cells and the formation of new blood vessel, which exhibited
      significant differences with pancreatic decellularized scaffold group (p<0.05).
      These findings indicated that the endothelialized heparin-pancreatic
      decellularized scaffold may be used to solve the problem of blood supply and to
      support the function of insulin-secreting cells better after in vivo
      transplantation, and therefore, would be a potential candidate for pancreatic
      tissue engineering.

PMID- 29338567
TI  - Outcomes with lower intensity therapy in TP53-mutated acute myeloid leukemia.

PMID- 29338568
TI  - Lactoferrin plus health education versus total dose infusion (TDI) of low
      molecular weight (LMW) iron dextran for treating iron deficiency anemia (IDA) in
      pregnancy: a randomized controlled trial.
AB  - BACKGROUND: Iron deficiency anemia (IDA) is one of the most common medical
      disorder disturbing pregnancies particularly in low resources countries, and
      contributes significantly to morbidities and mortalities. Thus, early diagnosis
      and prompt management of IDA is highly recommended. AIM: To Test the efficacy and
      safety of oral lactoferrin plus health education provided by a nurse versus total
      dose infusion (TDI) of low-molecular weight (LMW) iron dextran for treating IDA
      in the second and third trimester of pregnancy. DESIGN: A prospective
      interventional, randomized, parallel-group, single-center longitudinal study.
      SETTING: Woman's Health Assiut University Hospital, Assiut, Egypt, at the
      outpatient clinic and inpatient unit. It comprised 120 cases divided into two
      groups as pineapple flavored lactoferrin oral sachets 100 mg twice daily with
      health education (group A) and TDI of LMW iron dextran (group B). MAIN OUTCOME
      MEASURES: The primary efficacy parameter was clinical improvement and the amount
      of increase in hemoglobin concentration by 4 weeks after therapy, secondary
      outcome measures included measurement of the rest of RBC, and iron indices, the
      adverse effects related to iron therapy and the patient compliance to the
      treatment. RESULTS: There was insignificant difference between both groups
      regarding sociodemographic data, parity and mean gestational age. Both groups
      showed a significant clinical improvement of anemia 4 weeks post-therapy. There
      was no statistically significant difference in mean Hb level improvement in both
      groups after 1 month of therapy. However, mean corpuscular volume (MCV) and mean
      corpuscular hemoglobin (MCH) improved significantly more in group B than A while
      iron indices (serum iron and serum ferritin) were significantly more in group A
      than group B. CONCLUSIONS: Pineapple flavored lactoferrin oral sachets plus
      health education can be widely used as an alternative to TDI iron dextran
      supplementation due to clinical as well as laboratory improvement of IDA during
      pregnancy after 1 month of treatment. Proper health education of the pregnant
      women with nurse recommendations of balanced diet containing good sources of iron
      would increase awareness of pregnant women and help eradicate IDA with its
      serious sequel during pregnancy.

PMID- 29338569
TI  - Death rituals, religious beliefs, and grief of Turkish women.
AB  - Grief following a death loss is a common experience that all individuals face at
      some point in life. There, however, are only a few in-depth studies regarding
      grief in cultures around the world and specific roles that rituals and beliefs
      related to death may have in the grieving process. Results of interview data from
      eight grieving Turkish women revealed three themes: (a) metaphors of loss, (b)
      funeral rituals, and (c) rituals in relation to control and personal factors.
      Overall, participants' sense of control appeared to influence their grief
      experiences and perceptions of rituals.

PMID- 29338570
TI  - A Novel Rubric to Evaluate Wearable Cameras for Assessment of Interrater
      Reliability.
AB  - Research has reported on traditional methods of assessing interrater reliability
      but, currently, no such standard protocol exists for selection of alternative
      methods of assessing interrater reliability, such as wearable video cameras. The
      professions of occupational therapy and occupational science take a unique
      ecological perspective when evaluating individuals, which focuses on the
      naturalistic perspective of an individual, ideally resulting in optimal
      performance. Given current advancements in technology, wearable, low-cost,
      unobtrusive, first-person view digital video cameras are readily available for
      use in research. The researchers generated an original rubric for critiquing
      cameras, then trialed four cameras for use in a future interrater reliability
      study. This standardized protocol fills a gap in the field and can be used by
      future researchers searching for a standardized method of camera selection.

PMID- 29338571
TI  - Erratum.

PMID- 29338572
TI  - Implementation of additional prescribing authorization among oncology pharmacists
      in Alberta.
AB  - Purpose To describe the practice settings and prescribing practices of oncology
      pharmacists with additional prescribing authorization. Methods A descriptive,
      cross-sectional survey of all oncology pharmacists in Alberta was conducted using
      a web-based questionnaire over four weeks between March and April 2016.
      Pharmacists were identified from the Cancer Services Pharmacy Directory and
      leadership staff in Alberta Health Services. Descriptive statistics were used to
      describe the practice setting, prescribing practices, motivators to apply for
      additional prescribing authorization, and the facilitators and barriers of
      prescribing. Logistic regression was used to explore factors associated with
      having additional prescribing authorization. Results The overall response rate
      was 41% (71 of 175 pharmacists). Oncology pharmacists with additional prescribing
      authorization made up 38% of respondents. They primarily worked in urban,
      tertiary cancer centers, and practiced in ambulatory care. The top 3 clinical
      activities they participated in were medication reconciliation, medication
      counseling/education, and ambulatory patient assessment. Respondents thought
      additional prescribing authorization was most useful for ambulatory patient
      assessment and follow-up. Antiemetics were prescribed the most often. The median
      number of prescriptions written in an average week of clinical work was 5.
      Competence, self-confidence, and the potential impact on patient care/perceived
      impact on work environment were the strongest facilitators of prescribing. The
      strongest motivators to apply for additional prescribing authorization were
      relevancy to practice, the potential for increased efficiency, and advancing the
      profession. Conclusion The current majority of oncology pharmacist prescribing in
      Alberta occurs in ambulatory care with a large focus on antiemetic prescribing.
      Pharmacists found additional prescribing authorization most useful for ambulatory
      patient assessment and follow-up.

PMID- 29338573
TI  - Triphenylphosphine-docetaxel conjugate-incorporated albumin nanoparticles for
      cancer treatment.
AB  - AIM: The objective of this study was to develop a mitochondria-targeted
      anticancer drug, docetaxel (DTX), for chemotherapy. MATERIALS & METHODS: The DTX
      was conjugated to 4-carboxybutyl triphenylphosphonium (TPP) to enhance
      mitochondrial targeting, and the TPP-DTX conjugate was further loaded into folate
      cholesteryl albumin (FA-chol-BSA) nanoparticles (NPs) to improve its
      biocompatibility. RESULTS & CONCLUSION: In vitro studies showed that TPP-DTX and
      its NP primarily accumulated in the mitochondria; generated high reactive oxygen
      species, leading to mitochondrial disruption and cell apoptosis; and had a higher
      cytotoxicity against cancer cells. In vivo antitumor studies indicated that the
      NP significantly suppressed tumor growth compared with free drugs in xenograft
      tumor-bearing mice. Our results demonstrated that TPP-DTX@FA-chol-BSA NPs could
      be a promising mitochondria-targeted anticancer prodrug for chemotherapy.

PMID- 29338574
TI  - Protein nanoparticles are nontoxic, tuneable cell stressors.
AB  - AIM: Nanoparticle-cell interactions can promote cell toxicity and stimulate
      particular behavioral patterns, but cell responses to protein nanomaterials have
      been poorly studied. RESULTS: By repositioning oligomerization domains in a
      simple, modular self-assembling protein platform, we have generated closely
      related but distinguishable homomeric nanoparticles. Composed by building blocks
      with modular domains arranged in different order, they share amino acid
      composition. These materials, once exposed to cultured cells, are differentially
      internalized in absence of toxicity and trigger distinctive cell adaptive
      responses, monitored by the emission of tubular filopodia and enhanced drug
      sensitivity. CONCLUSION: The capability to rapidly modulate such cell responses
      by conventional protein engineering reveals protein nanoparticles as tuneable,
      versatile and potent cell stressors for cell-targeted conditioning.

PMID- 29338575
TI  - Characterization of medium-chain-length polyhydroxyalkanoate biosynthesis by
      Pseudomonas mosselii TO7 using crude glycerol.
AB  - Polyhydroxyalkanoates (PHAs) are biopolyesters produced by microorganisms that
      are environmentally friendly. PHAs can be used to replace traditional plastic to
      reduce environmental pollution in various fields. PHA production costs are high
      because PHA must be produced from a carbon substrate. The purpose of this study
      was to find the strain that can used the BDF by-product as the sole carbon source
      to produce high amounts of medium-chain-length PHA. Three isolates were evaluated
      for potential PHA production by using biodiesel-derived crude glycerol as the
      sole carbon source. Among them, Pseudomonas mosselii TO7 yielded high PHA
      content. The PHA produced from P. mosselii TO7 were medium-chain-length-PHAs. The
      PHA content of 48% cell dry weight in 48 h with a maximum PHA productivity of
      13.16 mg PHAs L-1 h-1. The narrow polydispersity index value of 1.3 reflected the
      homogeneity of the polymer chain, which was conducive to industrial applications.

PMID- 29338576
TI  - Effect of clinical response to active drugs and placebo on antipsychotics and
      mood stabilizers relative efficacy for bipolar depression and mania: A meta
      regression analysis.
AB  - BACKGROUND: Randomised placebo-controlled trials investigating treatments for
      bipolar disorder have been hampered by wide variations of active drugs and
      placebo clinical response rates. It is important to estimate whether the active
      drug or placebo response has a greater influence in determining the relative
      efficacy of drugs for psychosis (antipsychotics) and relapse prevention (mood
      stabilisers) for bipolar depression and mania. METHODS: We identified 53
      randomised, placebo-controlled trials assessing antipsychotic or mood stabiliser
      monotherapy ('active drugs') for bipolar depression or mania. We carried out
      random-effects meta-regressions, estimating the influence of active drugs and
      placebo response rates on treatment relative efficacy. RESULTS: Meta-regressions
      showed that treatment relative efficacy for bipolar mania was influenced by the
      magnitude of clinical response to active drugs ( p=0.002), but not to placebo (
      p=0.60). On the other hand, treatment relative efficacy for bipolar depression
      was influenced by response to placebo ( p=0.047), but not to active drugs (
      p=0.98). CONCLUSIONS: Despite several limitations, our unexpected findings showed
      that antipsychotics / mood stabilisers relative efficacy for bipolar depression
      seems unrelated to active drugs response rates, depending only on clinical
      response to placebo. Future research should explore strategies to reduce placebo
      related issues in randomised, placebo-controlled trials for bipolar depression.

PMID- 29338577
TI  - Modeling Sluggishness in Binaural Unmasking of Speech for Maskers With Time
      Varying Interaural Phase Differences.
AB  - In studies investigating binaural processing in human listeners, relatively long
      and task-dependent time constants of a binaural window ranging from 10 ms to 250
      ms have been observed. Such time constants are often thought to reflect "binaural
      sluggishness." In this study, the effect of binaural sluggishness on binaural
      unmasking of speech in stationary speech-shaped noise is investigated in 10
      listeners with normal hearing. In order to design a masking signal with
      temporally varying binaural cues, the interaural phase difference of the noise
      was modulated sinusoidally with frequencies ranging from 0.25 Hz to 64 Hz. The
      lowest, that is the best, speech reception thresholds (SRTs) were observed for
      the lowest modulation frequency. SRTs increased with increasing modulation
      frequency up to 4 Hz. For higher modulation frequencies, SRTs remained constant
      in the range of 1 dB to 1.5 dB below the SRT determined in the diotic situation.
      The outcome of the experiment was simulated using a short-term binaural speech
      intelligibility model, which combines an equalization-cancellation (EC) model
      with the speech intelligibility index. This model segments the incoming signal
      into 23.2-ms time frames in order to predict release from masking in modulated
      noises. In order to predict the results from this study, the model required a
      further time constant applied to the EC mechanism representing binaural
      sluggishness. The best agreement with perceptual data was achieved using a
      temporal window of 200 ms in the EC mechanism.

PMID- 29338579
TI  - Multi-spectroscopic and molecular modeling studies to reveal the interaction
      between propyl acridone and calf thymus DNA in the presence of histone H1: binary
      and ternary approaches.
AB  - DNA is the primary target of many anticancer drugs involved in important
      intercellular processes, especially in transcriptional regulation, and histone is
      known to inhibit gene expression. Small molecules can bind to histone-DNA and
      impair the cell division, growth, inhibition, and apoptosis in cancer cells. In
      this research, the interaction of a histone H1-calf thymus DNA (ct DNA) complex
      and propyl acridone (PA) was investigated in Tris-HCl buffer, pH 6.8, using multi
      spectroscopic, viscosity, and molecular modeling techniques. The Stern Volmer
      plot of the (H1-ct DNA) PA complex demonstrated two sets of binding sites with
      various binding affinities at three different temperatures. Thermodynamic
      parameters (DeltaH degrees  < 0 and DeltaS degrees  < 0) indicated that hydrogen
      bonds and van der Waals forces played the main roles in the binding of the drug
      to H1-ct DNA. The interaction between PA and ct DNA as well as (H1-ct-DNA) in the
      presence of acridine orange and ethidium bromide showed two different interaction
      behaviors in ternary systems. According to results from UV absorption
      spectroscopy and melting temperature (Tm) measurements, the binding mode of PA
      with ct DNA and the (H1-ct DNA) complex was indicative of an intercalative
      binding for the binary system and of both intercalative with groove binding with
      molecular fraction for the ternary system. Furthermore, the PA-induced detectable
      changes in the circular dichroism spectrum of ct DNA as well as changes in its
      viscosity. All of the experimental results proved that the intercalative binding
      between PA and ct DNA as well as the (H1-ct DNA) complex as binary and ternary
      systems must be predominant. The results obtained from experimental data were in
      good agreement with molecular modeling with regard to the determination of the
      binding site of PA to ct DNA in the absence and presence of histone H1.

PMID- 29338578
TI  - Cannabis Use is Associated with Lower Odds of Prescription Opioid Analgesic Use
      Among HIV-Infected Individuals with Chronic Pain.
AB  - BACKGROUND: Chronic pain is common in the United States and prescribed opioid
      analgesics use for noncancer pain has increased dramatically in the past two
      decades, possibly accounting for the current opioid addiction epidemic. Co-morbid
      drug use in those prescribed opioid analgesics is common, but there are few data
      on polysubstance use patterns. OBJECTIVE: We explored patterns of use of
      cigarette, alcohol, and illicit drugs in HIV-infected people with chronic pain
      who were prescribed opioid analgesics. METHODS: We conducted a secondary data
      analysis of screening interviews conducted as part of a parent randomized trial
      of financial incentives to improve HIV outcomes among drug users. In a
      convenience sample of people with HIV and chronic pain, we collected self-report
      data on demographic characteristics; pain; patterns of opioid analgesic use (both
      prescribed and illicit); cigarette, alcohol, and illicit drug use (including
      cannabis, heroin, and cocaine) within the past 30 days; and current treatment for
      drug use and HIV. RESULTS: Almost half of the sample of people with HIV and
      chronic pain reported current prescribed opioid analgesic use (N = 372, 47.1%).
      Illicit drug use was common (N = 505, 63.9%), and cannabis was the most commonly
      used illicit substance (N = 311, 39.4%). In multivariate analyses, only cannabis
      use was significantly associated with lower odds of prescribed opioid analgesic
      use (adjusted odds ratio = 0.57; 95% confidence interval: 0.38-0.87).
      Conclusions/Importance: Our data suggest that new medical cannabis legislation
      might reduce the need for opioid analgesics for pain management, which could help
      to address adverse events associated with opioid analgesic use.

PMID- 29338580
TI  - Paeonol nanoemulsion for enhanced oral bioavailability: optimization and
      mechanism.
AB  - AIM: The aim of this work was to optimize a nanoemulsion formulation and explain
      its absorption mechanism in improving the oral bioavailability of paeonol.
      METHOD: The bioavailability of paeonol was compared between paeonol nanoemulsion
      group and paeonol suspension group. The in situ single-pass intestine perfusion
      method, in vitro everted gut sacs method, Western blot analysis and Caco-2 cell
      transport studies were used to investigate the absorption mechanism of
      nanoemulsion. RESULTS: Nanoemulsion was proved to enhance the bioavailability of
      paeonol. P-glycoprotein (P-gp) mediated efflux might be the main reason affecting
      the oral absorption of paeonol. The prepared nanoemulsion prevented the P-gp
      mediated efflux and enhanced the bioavailability of paeonol. CONCLUSION: The
      overall results revealed that nanoemulsion was an effective vehicle to improve
      the oral bioavailability of paeonol which resulted from the prevention of P-gp
      efflux probably.

PMID- 29338581
TI  - Perceived Discrimination as a Risk Factor for Use of Emerging Tobacco Products:
      More Similarities Than Differences Across Demographic Groups and Attributions for
      Discrimination.
AB  - BACKGROUND: Perceived discrimination has been associated with cigarette smoking
      and other substance use among members of disadvantaged minority groups. However,
      most studies have focused on a single minority group, have not considered the
      individual's attribution for the discrimination, and have not considered emerging
      tobacco products. OBJECTIVE: This study examined the associations between
      perceived discrimination and use of six tobacco products (cigarettes, e
      cigarettes, cigars, pipe tobacco, hookah, and smokeless tobacco) in a diverse
      sample of 1,068 adults in the United States. METHODS: Participants were recruited
      on Amazon's Mechanical Turk and participated in an online survey. Logistic
      regression models were used to examine the association between perceived
      discrimination and use of each tobacco product. Interactions between
      discrimination and demographic characteristics, and between discrimination and
      perceived reasons for discrimination, were evaluated. RESULTS: Controlling for
      age, sex, race/ethnicity, education, and socioeconomic status, perceived
      discrimination was a risk factor for current use of five of the six tobacco
      products. These associations were consistent across racial/ethnic groups and
      regardless of the individual's attribution for the reason for the discrimination.
      CONCLUSIONS: Results indicate that perceived discrimination is a risk factor for
      the use of multiple tobacco products, and that this association is not limited to
      particular demographic groups or types of discrimination. Public health programs
      could potentially reduce tobacco-related disease by teaching healthier ways to
      cope with discrimination.

PMID- 29338582
TI  - A human pericardium biopolymeric scaffold for autologous heart valve tissue
      engineering: cellular and extracellular matrix structure and biomechanical
      properties in comparison with a normal aortic heart valve.
AB  - The objective of our study was to compare the cellular and extracellular matrix
      (ECM) structure and the biomechanical properties of human pericardium (HP) with
      the normal human aortic heart valve (NAV). HP tissues (from 12 patients) and NAV
      samples (from 5 patients) were harvested during heart surgery. The main cells in
      HP were pericardial interstitial cells, which are fibroblast-like cells of
      mesenchymal origin similar to the valvular interstitial cells in NAV tissue. The
      ECM of HP had a statistically significantly (p < 0.001) higher collagen I
      content, a lower collagen III and elastin content, and a similar
      glycosaminoglycans (GAGs) content, in comparison with the NAV, as measured by ECM
      integrated density. However, the relative thickness of the main load-bearing
      structures of the two tissues, the dense part of fibrous HP (49 +/- 2%) and the
      lamina fibrosa of NAV (47 +/- 4%), was similar. In both tissues, the secant
      elastic modulus (Es) was significantly lower in the transversal direction (p <
      0.05) than in the longitudinal direction. This proved that both tissues were
      anisotropic. No statistically significant differences in UTS (ultimate tensile
      strength) values and in calculated bending stiffness values in the longitudinal
      or transversal direction were found between HP and NAV. Our study confirms that
      HP has an advantageous ECM biopolymeric structure and has the biomechanical
      properties required for a tissue from which an autologous heart valve replacement
      may be constructed.

PMID- 29338583
TI  - Endocannabinoid engagement of CB2 regulates RSV-induced immunity.

PMID- 29338584
TI  - Effect of acute ingestion of beta-hydroxybutyrate salts on the response to graded
      exercise in trained cyclists.
AB  - Acute ingestion of ketone salts induces nutritional ketosis by elevating beta
      hydroxybutyrate (betaHB), but few studies have examined the metabolic effects of
      ingestion prior to exercise. Nineteen trained cyclists (12 male, 7 female)
      undertook graded exercise (8 min each at ~30%, 40%, 50%, 60%, 70%, and 80%
      VO2peak) on a cycle ergometer on two occasions separated by either 7 or 14 days.
      Trials included ingestion of boluses of either (i) plain water (3.8 mL kg body
      mass-1) (CON) or (ii) betaHB salts (0.38 g kg body mass-1) in plain water (3.8 mL
      kg body mass-1) (KET), at both 60 min and 15 min prior to exercise. During KET,
      plasma [betaHB] increased to 0.33 +/- 0.16 mM prior to exercise and 0.44 +/- 0.15
      mM at the end of exercise (both p < .05). Plasma glucose was 0.44 +/- 0.27 mM
      lower (p < .01) 30 min after ingestion of KET and remained ~0.2 mM lower
      throughout exercise compared to CON (p < .001). Respiratory exchange ratio (RER)
      was higher during KET compared to CON (p < .001) and 0.03-0.04 higher from
      30%VO2peak to 60%VO2peak (all p < .05). No differences in plasma lactate, rate of
      perceived exertion, or gross or delta efficiency were observed between trials.
      Gastrointestinal symptoms were reported in 13 out of 19 participants during KET.
      Acute ingestion of betaHB salts induces nutritional ketosis and alters the
      metabolic response to exercise in trained cyclists. Elevated RER during KET may
      be indicative of increased ketone body oxidation during exercise, but at the
      plasma betaHB concentrations achieved, ingestion of betaHB salts does not affect
      lactate appearance, perceived exertion, or muscular efficiency.

PMID- 29338585
TI  - The Effects of a Nutrition Media Literacy Intervention on Parents' and Youths'
      Communication about Food.
AB  - Interventions addressing links between media exposure and obesity risk for school
      age youth have not explicitly addressed the role of family communication about
      media. Youths' influence attempts on parents to purchase advertised foods can
      create conflict and negatively affect parental food choices. This study tested
      whether a family-based media literacy curriculum improves parents' media
      management skills and decreases youths' susceptibility to appealing but
      unrealistic food marketing. A matched-group pretest/posttest field experiment of
      parent-youth dyads with control group (N = 100 dyads, youth M = 11 years of age)
      tested the six-session curriculum. Hypotheses were analyzed using a Bayesian
      structural equation model. The curriculum increased parents' active negative
      mediation to foster youths' critical thinking about food marketing, b* = 0.35,
      95% CCI [0.17, 0.50], increased parent Efficacy for making healthy dietary
      changes for their families, b* = 0.59, 95% CCI [0.41, 0.75], and fostered family
      discussion about nutrition labels (total effect = 0.22). Additionally, cumulative
      influences of Perceived Desirability and Wishful Identification on youths'
      requests for marketed foods were reduced (total effect = 0.04). Media literacy
      education can empower parents and improve youths' critical thinking to reduce
      effects of food marketing on families and improve use of media to obtain
      nutrition information.

PMID- 29338586
TI  - Association of CXCL13 serum level and ultrasonographic findings of joints in
      patients with systemic lupus erythematosus and Jaccoud's arthropathy.
AB  - Objectives The objective of this paper is to perform an ultrasonography (US)
      analysis of hands and wrists in two groups of patients with systemic lupus
      erythematosus (SLE), with and without Jaccoud's arthropathy, matched by age and
      disease duration and to correlate them with levels of CXCL13 clinical features,
      laboratory tests and disease activity score. Methods Sixty-four patients with SLE
      were enrolled, 32 with and 32 without Jaccoud's arthropathy. Each patient
      underwent physical examination, laboratory tests (including CXCL13 by ELISA) and
      bilateral US. Synovial hypertrophy, tenosynovitis and erosions were evaluated
      according to a semiquantitative grading system with a 0-3 rating. US findings
      were correlated with serum levels of CXCL13, other serological parameters and
      disease activity index. Results Synovitis was found in 25/64 patients (39%) and
      tenosynovitis in 14/64 (22%). These findings were more frequent in SLE patients
      with Jaccoud's arthropathy, particularly tenosynovitis ( p = 0.002) and synovitis
      ( p = 0.01). Median serum level of CXCL13 was 20.16 pg/ml in the whole population
      (23.21 pg/ml in the Jaccoud's arthropathy group and 11.48 pg/ml in the group
      without). There was an association between the presence of disease activity and
      high level of CXCL13 ( p = 0.004). However, no association was found between high
      levels of CXCL13 and "arthritis" in SLEDAI, swollen joints on physical
      examination or synovitis on US. Conclusions US findings in joints of SLE patients
      with Jaccoud's arthropathy confirm that synovitis and tenosynovitis are common in
      these patients. In addition, serum level of CXCL13 is associated with disease
      activity in SLE but does not seem to be a biomarker for arthritis in these
      patients.

PMID- 29338587
TI  - Antiphosphatidylserine/prothrombin (aPS/PT) antibodies are associated with
      Raynaud phenomenon and migraine in primary thrombotic antiphospholipid syndrome.
AB  - Objectives Antibodies to phosphatidylserine/prothrombin complex (aPS/PT)
      detectable in sera of some patients with antiphospholipid syndrome (APS) have
      been shown to correlate with thrombosis. However, associations of aPS/PT
      antibodies with APS related disorders remain unclear. Aim To evaluate whether
      there are any associations between aPS/PT antibodies and Raynaud phenomenon,
      migraine and/or valvular lesions in primary thrombotic APS (PAPS). Methods We
      enrolled 67 consecutive patients (56 women) with thrombotic PAPS (VTE in 80.6%),
      aged 46.2 +/- 13.5 years. The exclusion criteria were: acute coronary syndromes
      or stroke within preceding 6 months, cancer, severe comorbidities and pregnancy.
      The IgG and IgM aPS/PT antibodies were determined by ELISA with the cut-off of 30
      units. We recorded Raynaud phenomenon, migraine and valvular lesions. Results
      Positive IgM or/and IgG aPS/PT antibodies were observed in 29 patients (43.3%),
      with a higher prevalence of IgM antibodies ( n = 27, 40.3%) compared with IgG
      isotype ( n = 12, 17.9%, p = 0.014). aPS/PT antibodies were observed most
      commonly in patients with triple aPL ( n = 12, 85.7%) compared with those with
      double ( n = 5, 35.7%) or single aPL antibodies (n = 12, 30.8%, p = 0.03), with
      no association with demographics, the ANA titre, the type of thrombotic events or
      medications. Raynaud phenomenon, migraine and valvular lesions were observed in
      15% ( n = 10), 30% ( n = 20) and 18% ( n = 12) of the patients, respectively.
      Raynaud phenomenon and migraine, but not valvular lesions, were markedly more
      frequent in PAPS patients presenting with positive aPS/PT antibodies ( n = 10,
      34.5% vs. n = 0, 0%; p = 0.0001). Conclusions In PAPS patients aPS/PT antibodies
      are related to the occurrence of both Raynaud phenomenon and migraine.

PMID- 29338588
TI  - Epstein-Barr virus infection and type I interferon signature in patients with
      systemic lupus erythematosus.
AB  - Epstein-Barr (EB) virus infection has long been speculated to evoke systemic
      lupus erythematosus (SLE). Since a virus infection can induce interferon (IFN)
      system activation, we aimed to discover the relationship between the two in the
      progression of SLE in a Chinese inpatient cohort. Methods Peripheral blood
      mononuclear cells and sera were isolated from 116 SLE patients and 76 healthy
      controls. Antibodies against EBV-VCA (IgM and IgG) and EBNA (IgG) along with
      IFNalpha in patient sera were detected with enzyme-linked immunosorbent assays.
      The EB virus DNA load was detected by real-time quantitative polymerase chain
      reaction. Peripheral blood mononuclear cells both from patients and controls were
      isolated immediately. The mRNA from these samples was subjected to real-time PCR
      for the latent genes EBNA1, EBNA2 and LMP1 of EB virus, as well as four IFN
      stimulated genes (ISGs) ( OASL, MX1, ISG15 and LY6E). The antibody results were
      used to determine the stage of EBV infection (lytic, latent, or previous).
      Results SLE patients had a higher rate of lytic infection defined as positive EBV
      VCA IgM antibody (39.66% vs 10.53%, p = 0.027), but not the EB virus DNA load.
      Patients with lytic EB virus infection had higher SLEDAI scores than patients
      with non-lytic infection (15.24 +/- 2.63 vs 13.79 +/- 3.24, p = 0.012). LMP1 was
      the only EBV gene that had a higher expression level in SLE patients than in
      healthy controls (3.26 +/- 2.95 vs 1.00 +/- 2.89, p = 0.000). It was also
      positively correlated with SLEDAI scores ( r = 0.462, p = 0.000). Levels of
      IFNalpha and the four ISGs were all significantly higher in SLE patients than in
      healthy controls ( p < 0.05). LMP1 was positively correlated with the four ISGs (
      r = 0.403 ~ 0.494, p < 0.05) in SLE patients but not in healthy controls ( r = 
      0.153 ~ 0.129, p > 0.05). Neither EBNA1 nor EBNA2 was correlated with the ISGs in
      SLE patients or in healthy controls. Conclusions The SLE patients had higher
      rates of lytic EB virus infection and higher latent gene LMP1 expression, which
      might be associated with the development and/or the progression of SLE via the
      type I IFN pathway. The underlying mechanism needs more study.

PMID- 29338589
TI  - Population Health: School Health Services and School Nursing.

PMID- 29338590
TI  - Histopathology and Antibodies.

PMID- 29338591
TI  - Association between health status and sociodemographic, clinical and treatment
      disparities in the Patient-centered Outcomes Related to TReatment Practices in
      Peripheral Arterial Disease: Investigating Trajectories (PORTRAIT) registry.
AB  - Patients with peripheral artery disease (PAD) and intermittent claudication (IC)
      have impaired functional status and quality of life. However, little is known
      about which factors are associated with poorer health status at the time of
      initial presentation for PAD specialty care. Characterization of such features
      might provide insight into disparities that impact health status in this
      population. A total of 1258 patients from the United States, the Netherlands and
      Australia with new or worsened IC were enrolled at their first PAD specialty care
      visit between June 2011 and December 2015. The mean Peripheral Artery
      Questionnaire (PAQ) Summary Score (range 0-100), a disease-specific health status
      measure, was 49.2 +/- 21.9. Hierarchical, multivariable linear regression was
      used to relate patient characteristics to baseline PAQ. Patient characteristics
      independently associated with poorer health status were age ( p < 0.001), female
      sex ( p < 0.001), not being married ( p = 0.02), economic burden (moderate/severe
      vs none, moderate/severe vs some; p = 0.03), difficulty getting care
      (moderate/severe vs none, moderate/severe vs some; p < 0.001), chronic lung
      disease ( p = 0.02), back pain ( p < 0.001), bilateral vs unilateral PAD ( p =
      0.02), intermittent claudication severity (moderate vs mild, severe vs mild, p <
      0.001), and lack of prior participation in an exercise program ( p = 0.005).
      Disparities in both vascular and non-vascular factors were associated with
      patients' health status at the time of presentation and should be addressed by
      all who care for patients with vascular disease.

PMID- 29338592
TI  - Whole-Genome-Sequencing characterization of bloodstream infection-causing
      hypervirulent Klebsiella pneumoniae of capsular serotype K2 and ST374.
AB  - Hypervirulent K. pneumoniae variants (hvKP) have been increasingly reported
      worldwide, causing metastasis of severe infections such as liver abscesses and
      bacteremia. The capsular serotype K2 hvKP strains show diverse multi-locus
      sequence types (MLSTs), but with limited genetics and virulence information. In
      this study, we report a hypermucoviscous K. pneumoniae strain, RJF293, isolated
      from a human bloodstream sample in a Chinese hospital. It caused a metastatic
      infection and fatal septic shock in a critical patient. The microbiological
      features and genetic background were investigated with multiple approaches. The
      Strain RJF293 was determined to be multilocis sequence type (ST) 374 and serotype
      K2, displayed a median lethal dose (LD50) of 1.5 * 102 CFU in BALB/c mice and was
      as virulent as the ST23 K1 serotype hvKP strain NTUH-K2044 in a mouse lethality
      assay. Whole genome sequencing revealed that the RJF293 genome codes for 32
      putative virulence factors and exhibits a unique presence/absence pattern in
      comparison to the other 105 completely sequenced K. pneumoniae genomes. Whole
      genome SNP-based phylogenetic analysis revealed that strain RJF293 formed a
      single clade, distant from those containing either ST66 or ST86 hvKP. Compared to
      the other sequenced hvKP chromosomes, RJF293 contains several strain-variable
      regions, including one prophage, one ICEKp1 family integrative and conjugative
      element and six large genomic islands. The sequencing of the first complete
      genome of an ST374 K2 hvKP clinical strain should reinforce our understanding of
      the epidemiology and virulence mechanisms of this bloodstream infection-causing
      hvKP with clinical significance.

PMID- 29338594
TI  - Cancer therapeutics through an evolutionary lens.

PMID- 29338593
TI  - Expression and role of granulocyte macrophage colony-stimulating factor receptor
      (GM-CSFR) and granulocyte colony-stimulating factor receptor (G-CSFR) on Ph
      positive acute B lymphoblastic leukemia.
AB  - OBJECTIVE: We observed that ph + ALL patients administrated with recombinant
      human G-CSF (rhG-CSF) after intense chemotherapy have presented a trend of
      disease relapse. Thus, we aim to thoroughly investigate the expression and role
      of GM-CSFR and G-CSFR on ph + ALL patients. METHOD: SUP-B15, BALL-1 and primary
      leukemia cells were used in this study. Transcript levels were analyzed by
      quantitative PCR while cell viability was measured using a CCK-8 assay. Flow
      cytometry was used to assess the different stages of cell cycle. RESULTS: We
      found that the mRNA expression levels of GM-CSFR and G-CSFR were higher in
      patients with ph + ALL, as well as in SUP-B15 cells. rhG-CSF was also observed to
      promote the viability of SUP-B15 cells while inversely inhibiting BALL-1 cell
      viability. In addition, we also determined that rhG-CSF (100 ng/ml) decreased the
      sensitivity of SUP-B15 cells to imatinib and nilotinib, while the results were
      exactly the contrary for dasatinib. CONCLUSION: We demonstrated high expression
      levels of GM-CSFR and G-CSFR, as well as their promotable role for viability in
      ph + ALL cells. We further found that rhG-CSF influenced the sensitivity of SUP
      B15 cells to TKIs.

PMID- 29338595
TI  - From NHS to devolved independent regional health services.

PMID- 29338597
TI  - Imagine ... a better future for the NHS.

PMID- 29338598
TI  - Using randomised, double-blind, N-of-1 trials of food challenge to diagnose food
      allergy and assess the effectiveness of food allergen avoidance.

PMID- 29338601
TI  - Reflections on the development of a therapeutic recreation-based bereavement camp
      for families whose child has died from serious illness.
AB  - While bereavement camps serve as a support for children, this study examines a
      therapeutic recreation-based camp for families who have lost a child. The study
      triangulated documents, researcher reflection, and staff interviews to highlight
      the themes of Searching & Finding, Getting to Know, Finding the Balance, and
      Joining. Developing opportunistically through internal and external factors, the
      camp's evolution represents a closing of the loop, from supporting families of
      living children to also supporting the families of children who have died.
      Understanding the camp's evolution may facilitate other programs by highlighting
      the challenges in developing the program and the lessons learned.

PMID- 29338603
TI  - Emerging roles of inositol pyrophosphates as key modulators of fungal
      pathogenicity.
AB  - Inositol pyrophosphates (PP-IPs) are energy-rich small molecules that are
      omnipresent in eukaryotic cells, from yeast to mammals, playing central roles in
      overall cellular homeostasis as a diverse and multifaceted class of intracellular
      messengers. Recent studies of the metabolic pathways and physiological roles of
      PP-IPs in the human pathogenic fungus Cryptococcus neoformans have revealed that
      the PP-IP5 (IP7) is a key metabolite essential for fungal metabolic adaptation to
      the host environment, immune recognition, and pathogenicity. This suggests the PP
      IP biosynthesis pathway, comprising phospholipase C1 (Plc1) and a series of
      sequentially acting inositol polyphosphate kinases (IPKs), as a new virulence
      related signaling pathway in C. neoformans. Given that fungal species have a
      reduced array of the kinases required for the synthesis of PP-IPs and that the
      homology between human and fungal IPKs is restricted to a few catalytically
      important residues, identification of IPK inhibitors specifically targeting the
      kinases of pathogenic fungi has emerged as a desirable and achievable strategy
      for antifungal drug development.

PMID- 29338602
TI  - Sequential drug treatment algorithm for agitation and aggression in Alzheimer's
      and mixed dementia.
AB  - INTRODUCTION: Behavioural and psychological symptoms of dementia (BPSD) include
      agitation and aggression in people with dementia. BPSD is common on inpatient
      psychogeriatric units and may prevent individuals from living at home or in
      residential/nursing home settings. Several drugs and non-pharmacological
      treatments have been shown to be effective in reducing behavioural and
      psychological symptoms of dementia. Algorithmic treatment may address the
      challenge of synthesizing this evidence-based knowledge. METHODS: A
      multidisciplinary team created evidence-based algorithms for the treatment of
      behavioural and psychological symptoms of dementia. We present drug treatment
      algorithms for agitation and aggression associated with Alzheimer's and mixed
      Alzheimer's/vascular dementia. Drugs were appraised by psychiatrists based on
      strength of evidence of efficacy, time to onset of clinical effect, tolerability,
      ease of use, and efficacy for indications other than behavioural and
      psychological symptoms of dementia. RESULTS: After baseline assessment and
      discontinuation of potentially exacerbating medications, sequential trials are
      recommended with risperidone, aripiprazole or quetiapine, carbamazepine,
      citalopram, gabapentin, and prazosin. Titration schedules are proposed, with
      adjustments for frailty. Additional guidance is given on use of electroconvulsive
      therapy, optimization of existing cholinesterase inhibitors/memantine, and use of
      pro re nata medications. CONCLUSION: This algorithm-based approach for drug
      treatment of agitation/aggression in Alzheimer's/mixed dementia has been
      implemented in several Canadian Hospital Inpatient Units. Impact should be
      assessed in future research.

PMID- 29338605
TI  - Noteworthy Literature published in 2017 for Cardiac Critical Care.
AB  - In 2017, many high-impact articles appeared in the literature. This is the third
      edition of an annual review of articles related to postoperative cardiac critical
      care that may affect the cardiac anesthesiologist. This year explores vasopressor
      and inotropic support, timing of renal replacement therapy, management of
      postoperative respiratory insufficiency, and targeted temperature therapy.

PMID- 29338604
TI  - Clinical significance of cerebral microbleeds on MRI: A comprehensive meta
      analysis of risk of intracerebral hemorrhage, ischemic stroke, mortality, and
      dementia in cohort studies (v1).
AB  - Background Cerebral microbleeds can confer a high risk of intracerebral
      hemorrhage, ischemic stroke, death and dementia, but estimated risks remain
      imprecise and often conflicting. We investigated the association between cerebral
      microbleeds presence and these outcomes in a large meta-analysis of all published
      cohorts including: ischemic stroke/TIA, memory clinic, "high risk" elderly
      populations, and healthy individuals in population-based studies. Methods Cohorts
      (with > 100 participants) that assessed cerebral microbleeds presence on MRI,
      with subsequent follow-up (>=3 months) were identified. The association between
      cerebral microbleeds and each of the outcomes (ischemic stroke, intracerebral
      hemorrhage, death, and dementia) was quantified using random effects models of
      (a) unadjusted crude odds ratios and (b) covariate-adjusted hazard rations.
      Results We identified 31 cohorts ( n = 20,368): 19 ischemic stroke/TIA ( n =
      7672), 4 memory clinic ( n = 1957), 3 high risk elderly ( n = 1458) and 5
      population-based cohorts ( n = 11,722). Cerebral microbleeds were associated with
      an increased risk of ischemic stroke (OR: 2.14; 95% CI: 1.58-2.89 and adj-HR:
      2.09; 95% CI: 1.71-2.57), but the relative increase in future intracerebral
      hemorrhage risk was greater (OR: 4.65; 95% CI: 2.68-8.08 and adj-HR: 3.93; 95%
      CI: 2.71-5.69). Cerebral microbleeds were an independent predictor of all-cause
      mortality (adj-HR: 1.36; 95% CI: 1.24-1.48). In three population-based studies,
      cerebral microbleeds were independently associated with incident dementia (adj
      HR: 1.35; 95% CI: 1.00-1.82). Results were overall consistent in analyses
      stratified by different populations, but with different degrees of heterogeneity.
      Conclusions Our meta-analysis shows that cerebral microbleeds predict an
      increased risk of stroke, death, and dementia and provides up-to-date effect
      sizes across different clinical settings. These pooled estimates can inform
      clinical decisions and trials, further supporting cerebral microbleeds role as
      biomarkers of underlying subclinical brain pathology in research and clinical
      settings.

PMID- 29338606
TI  - Utility of mean sphered cell volume and mean reticulocyte volume for the
      diagnosis of hereditary spherocytosis.
AB  - INTRODUCTION: Hereditary spherocytosis (HS) is the most common congenital
      hemolytic anemia, characterized by anemia, jaundice, and splenomegaly. The
      diagnosis of HS relies on symptoms of hemolysis, a family history of HS, and a
      positive laboratory test which is usually the osmotic fragility test (OFT). We
      conducted a study to assess the utility of mean corpuscular hemoglobin
      concentration (MCHC), mean corpuscular volume (MCV), mean sphered cell volume
      (MSCV), and mean reticulocyte volume (MRV) in the diagnosis of HS and if these
      are helpful in distinguishing cases of HS from immune hemolytic anemia. METHODS:
      A total of 102 patients suspected to have HS were enrolled. In addition 10 cases
      of immune hemolytic anemia (IHA) were included in the study and performance of
      the above screening tests was evaluated. The diagnosis of HS was based on
      incubated OFT, eosin 5'-maleimide (EMA) dye binding test, and flowcytometric OFT.
      RESULTS: A total of 29 patients were diagnosed as having HS. The sensitivity and
      specificity for diagnosis HS by MCHC > 35 g/dL was 44.82%, and DeltaMCV-MSCV > 10
      fL has a sensitivity and specificity of 82.75% and 95.9% for diagnosis of HS.
      Using an algorithm of DeltaMCV-MSCV > 10 fL and DeltaMRV-MSCV < 25, for the
      differentiation of HS from IHA had sensitivity of 68.9% and specificity of 98.8%.

PMID- 29338607
TI  - Immunotherapies in transplantation and cancer: 22nd NAT meeting/2nd NAT LabEx IGO
      joint meeting; 1-2 June 2017, Nantes, France.
AB  - This 22nd edition of the Nantes Actualites Transplantation annual meeting was co
      organized for the second time with the LabEx Immuno-Graft Oncology network. This
      international meeting was held on 1 and 2 June 2017 in Nantes (western France).
      The topic of this 2-day meeting was 'Immunotherapies in transplantation and
      cancer'. This meeting brought together 17 international invited speakers, young
      researchers and 220 attendees mainly from Europe and North America. It was a
      unique opportunity to bring together the pioneers and leading immunologists in
      the fields of transplantation and cancer, focusing on shared mechanisms that
      control immune responses in organ or bone marrow transplantation and in cancer.

PMID- 29338608
TI  - Immunotherapy of cancer: targeting cancer during active disease or during
      dormancy?
AB  - Immunotherapeutic targeting of advanced stage cancers has prolonged the survival
      of cancer patients, yet its curative efficacy is limited due to tumor
      immunoediting and escape. On the other hand, human vaccines have been able to
      eradicate smallpox and control several other infectious diseases. The success has
      resulted from the administration of vaccines in prophylactic settings, or during
      latency periods in order to protect an individual during future exposure to the
      disease rather than curing an established disease. Therefore, administration of
      immunotherapy at the right time is the key to success. However, instead of
      focusing on the prevention of cancer, current cancer immunotherapies are often
      being used in a therapeutic setting with the goal of eliminating tumor cells. The
      present review of evidence related to cancer immunotherapeutics suggests that
      immunotherapeutic targeting of tumor dormancy could be more promising than
      targeting of advanced stage disease to achieve a cure for cancer.

PMID- 29338609
TI  - Chemotherapy-induced immunomodulation in non-small-cell lung cancer: a rationale
      for combination chemoimmunotherapy.
AB  - Spurred by the survival benefits seen with the use of checkpoint blockade in non
      small-cell lung cancer (NSCLC), there has been a growing interest in the
      potential applications of immunotherapy. Despite this, the objective response
      rate for single-agent immunotherapy remains <=20% in patients with advanced
      NSCLC. A combinatorial approach that utilizes both chemotherapy and immunotherapy
      is a potential strategy to increase antitumor efficacy. Accumulating evidence has
      shown that the immunomodulatory effects of chemotherapeutic agents can be
      exploited in a combinational approach. Herein, we review the influence of
      specific chemotherapeutic agents on the tumor immune microenvironment in
      preclinical and clinical studies, and establish the rationale for combination
      chemoimmunotherapy for the treatment of NSCLC.

PMID- 29338611
TI  - Hematopoietic and mesenchymal stem cells: a promising new therapy for
      spondyloarthritis?
AB  - In the last years, a considerable progress has been made in the treatment of
      spondyloarthritides. Nonetheless, there remain a considerable number of patients
      who are unresponsive to all current therapies. Since the late 1990s, numerous
      trials have investigated the use of stem cell transplantation as a new approach
      for the treatment of autoimmune disease, particularly with hematopoietic stem
      cell transplantation. More recently, the research has focused on mesenchymal stem
      cell application due to their low immunogenicity and immunomodulatory properties.
      In this article, we summarize available data on hematopoietic stem cell and
      mesenchymal stem cell use for the treatment of spondyloarthritides and discuss
      the data gaps and possible research agenda in this area.

PMID- 29338610
TI  - CNS side effects of immune checkpoint inhibitors: preclinical models, genetics
      and multimodality therapy.
AB  - Following cancer treatment, patients often report behavioral and cognitive
      changes. Novel cancer immunotherapeutics have the potential to produce sustained
      cancer survivorship, meaning patients will live longer with the side effects of
      treatment. Given the role of inflammatory pathways in mediating behavioral and
      cognitive impairments seen in cancer, we aim in this review to discuss emerging
      evidence for the contribution of immune checkpoint blockade to exacerbate these
      CNS effects. We discuss ongoing studies regarding the ability of immune
      checkpoint inhibitors to reach the brain and how treatment responses to
      checkpoint inhibitors may be modulated by genetic factors. We further consider
      the use of preclinical tumor-models to study the role of tumor status in CNS
      effects of immune checkpoint inhibitors and multimodality therapy.

PMID- 29338613
TI  - Combined systems of different antibiotics with nano-CuO against Escherichia coli
      and the mechanisms involved.
AB  - AIM: The combined efficacy of CuO nanoparticles (NPs) with 22 kinds of
      antibiotics against Escherichia coli was systematic studied, and CuO with
      cephalexin synergistic system was screened out. METHODS: Antimicrobial
      susceptibility test included disk diffusion test, checkerboard method and time
      kill assay. The interactions of CuO NPs and antibiotics were analyzed by x-ray
      photoelectron spectroscopy, Fourier transform infrared spectra and Zeta. The
      interactions between bacteria and antibacterial agents were studied by surface
      plasmon resonance sensor for the first time. RESULTS & CONCLUSION: Synergistic
      effect (1+1>2) was observed when CuO NPs combined with cephalexin against E.
      coli. The concentrated cephalexin molecules interacted more strongly with the E.
      coli cells to make cell wall become loose. Then, CuO NPs were more easily to
      damage and penetrate cells. Besides, the presence of antibiotics did not enhance
      Cu2+ release, Cu2+ uptake and reactive oxygen species generation. But the
      presence of cephalexin greatly enhanced cell permeability in comparison to
      others.

PMID- 29338614
TI  - The two mutations of actin-myosin interface and their effect on the dynamics,
      structures, and functions of skeletal muscle actin.
AB  - Congenital myopathy is a broad category of muscular diseases with symptoms
      appearing at the time of birth. One type of congenital myopathy is Congenital
      Fiber Type Disproportion (CFTD), a severely debilitating disease. The G48D and
      G48C mutations in the D-loop and the actin-myosin interface are the two causes of
      CFTD. These mutations have been shown to significantly affect the structure and
      function of muscle fibers. To the author's knowledge, the effects of these
      mutations have not yet been studied. In this work, the power stroke structure of
      the head domain of myosin and the wild and mutated types of actin were modeled.
      Then, a MD simulation was run for the modeled structures to study the effects of
      these mutations on the structure, function, and molecular dynamics of actin. The
      wild and mutated actins docked with myosin showed differences in hydrogen bonding
      patterns, free binding energies, and hydrogen bond occupation frequencies. The
      G48D and G48C mutations significantly impacted the conformation of D-loops
      because of their larger size compared to Glycine and their ability to interfere
      with the polarity or hydrophobicity of this neutralized and hydrophobic loop.
      Therefore, the mutated loops were unable to fit properly into the hydrophobic
      groove of the adjacent G-actin. The abnormal structure of D-loops seems to result
      in the abnormal assembly of F-actins, giving rise to the symptoms of CFTD. It was
      also noted that G48C and G48D did not form hydrogen bonds with myosin in the
      residue 48 location. Nevertheless, in this case, muscles are unable to contract
      properly due to muscle atrophy.

PMID- 29338612
TI  - Gene Profiling of Nucleus Basalis Tau Containing Neurons in Chronic Traumatic
      Encephalopathy: A Chronic Effects of Neurotrauma Consortium Study.
AB  - Military personnel and athletes exposed to traumatic brain injury may develop
      chronic traumatic encephalopathy (CTE). Brain pathology in CTE includes
      intracellular accumulation of abnormally phosphorylated tau proteins (p-tau), the
      main constituent of neurofibrillary tangles (NFTs). Recently, we found that
      cholinergic basal forebrain (CBF) neurons within the nucleus basalis of Meynert
      (nbM), which provide the major cholinergic innervation to the cortex, display an
      increased number of NFTs across the pathological stages of CTE. However,
      molecular mechanisms underlying nbM neurodegeneration in the context of CTE
      pathology remain unknown. Here, we assessed the genetic signature of nbM neurons
      containing the p-tau pretangle maker pS422 from CTE subjects who came to autopsy
      and received a neuropathological CTE staging assessment (Stages II, III, and IV)
      using laser capture microdissection and custom-designed microarray analysis.
      Quantitative analysis revealed dysregulation of key genes in several gene
      ontology groups between CTE stages. Specifically, downregulation of the nicotinic
      cholinergic receptor subunit beta-2 gene (CHRNB2), monoaminergic enzymes catechol
      O-methyltransferase (COMT) and dopa decarboxylase (DDC), chloride channels CLCN4
      and CLCN5, scaffolding protein caveolin 1 (CAV1), cortical
      development/cytoskeleton element lissencephaly 1 (LIS1), and intracellular
      signaling cascade member adenylate cyclase 3 (ADCY3) was observed in pS422
      immunreactive nbM neurons in CTE patients. By contrast, upregulation of calpain 2
      (CAPN2) and microtubule-associated protein 2 (MAP2) transcript levels was found
      in Stage IV CTE patients. These single-population data in vulnerable neurons
      indicate alterations in gene expression associated with neurotransmission, signal
      transduction, the cytoskeleton, cell survival/death signaling, and microtubule
      dynamics, suggesting novel molecular pathways to target for drug discovery in
      CTE.

PMID- 29338615
TI  - Assessment of Canine Mast Cell Tumor Mortality Risk Based on Clinical,
      Histologic, Immunohistochemical, and Molecular Features.
AB  - Mast cell tumor (MCT) is a frequent cutaneous neoplasm in dogs that is
      heterogeneous in clinical presentation and biological behavior, with a variable
      potential for recurrence and metastasis. Accurate prediction of clinical outcomes
      has been challenging. The study objective was to develop a system for
      classification of canine MCT according to the mortality risk based on individual
      assessment of clinical, histologic, immunohistochemical, and molecular features.
      The study included 149 dogs with a histologic diagnosis of cutaneous or
      subcutaneous MCT. By univariate analysis, MCT metastasis and related death was
      significantly associated with clinical stage ( P < .0001, rP = -0.610), history
      of tumor recurrence ( P < .0001, rP = -0.550), Patnaik ( P < .0001, rP = -0.380)
      and Kiupel grades ( P < .0001, rP = -0.500), predominant organization of
      neoplastic cells ( P < .0001, rP = -0.452), mitotic count ( P < .0001, rP = 
      0.325), Ki-67 labeling index ( P < .0001, rP = -0.414), KITr pattern ( P = .02,
      rP = 0.207), and c-KIT mutational status ( P < .0001, rP = -0.356). By
      multivariate analysis with Cox proportional hazard model, only 2 features were
      independent predictors of overall survival: an amendment of the World Health
      Organization clinical staging system (hazard ratio [95% CI]: 1.824 [1.210-4.481];
      P = .01) and a history of tumor recurrence (hazard ratio [95% CI]: 9.250 [2.158
      23.268]; P < .001]. From these results, we propose an amendment of the WHO
      staging system, a method of risk analysis, and a suggested approach to clinical
      and laboratory evaluation of dogs with cutaneous MCT.

PMID- 29338616
TI  - Systemic Loss of C-terminal Src Kinase Expression Elicits Spontaneous Suppurative
      Inflammation in Conditional Knockout Mice.
AB  - C-terminal Src kinase (Csk) is one of the critical negative regulators of the Src
      family of kinases. The Src family of kinases are nonreceptor tyrosine kinases
      that regulate inflammation, cell proliferation, motility, and adhesion. To
      investigate potential histologic lesions associated with systemic loss of Csk
      gene activity in adult mice, conditional Csk-knockout mice were examined. Cre
      mediated systemic excision of Csk induced by tamoxifen treatment resulted in
      multiorgan inflammation. Specifically, induction of Csk gene excision with three
      days of tamoxifen treatment resulted in greater than 90% gene excision.
      Strikingly, these mice developed enteritis that ranged from minimal and
      suppurative to severe, fibrinonecrosuppurative and hemorrhagic. Other
      inflammatory lesions included suppurative pneumonia, gastritis, and myocarditis,
      and increased numbers of inflammatory cells within the hepatic parenchyma. When
      tamoxifen treatment was reduced from three days to one day in an effort to lower
      the level of Csk gene excision and limit lesion development, the mice developed
      severe suppurative to pyogranulomatous pneumonia and minimal to mild suppurative
      enteritis. Lesions observed secondary to Csk gene excision suggest important
      roles for Csk in downregulating the proinflammatory activity of the Src family of
      kinases and limiting neutrophil-mediated inflammation.

PMID- 29338617
TI  - Carbon nanospheres mediated nuclear delivery of SMAR1 protein (DNA binding
      domain) controls breast tumor in mice model.
AB  - AIM: To investigate anticancer activity of the DNA binding domain of SMAR1 (His
      5) in vitro and in vivo. MATERIALS & METHODS: His 5 was conjugated to
      hydrothermally synthesized carbon nanospheres (CNs). Anticancer activity of CNs
      His 5 was evaluated in vitro and in vivo. RESULTS: CNs- His 5 significantly
      reduced cyclin D1 levels in MDA-MB-231 cells. Tumor bearing Balb/c mice injected
      with CNs-His 5 showed approximately 62% tumor regression and significantly
      reduced 18FDG uptake. Caspases assay and IHC staining confirmed tumor growth
      inhibition, which could be attributed to apoptotic, antiproliferative and
      antiangiogenic activities of His 5. CONCLUSION: DNA binding domain of the SMAR1
      protein (His 5) has potent anticancer activity and its CNs mediated delivery
      could control breast tumor in mice model.

PMID- 29338618
TI  - Presence of trauma and suicide risk: Personal control as a moderator.
AB  - Given past findings that have linked trauma and lack of personal control to
      greater suicidal risk in adults, the present study examined how trauma presence
      and personal control are uniquely involved in predicting suicidal risk in a
      sample of 469 college students. Regression analyses indicated that both trauma
      presence and personal control were significant predictors of suicidal risk, as
      was their interaction. The present findings suggest a need to consider both
      trauma presence and low personal control in assessing for suicidal risk in
      college students.

PMID- 29338619
TI  - Novel Phellodendri Cortex (Huang Bo)-derived carbon dots and their hemostatic
      effect.
AB  - AIM: To explore the hemostatic effect of Phellodendri Cortex-derived carbon dots.
      MATERIALS & METHODS: Transmission electron microscopy, high-resolution
      transmission electron microscopy, Fourier transform infrared spectroscopy,
      ultraviolet-visible spectroscopy, fluorescence spectroscopy, x-ray photoelectron
      spectroscopy and a cell counting kit-8 assay were studied. Hemostatic effect of
      Phellodendri Cortex Carbonisatus-carbon dots (PCC-CDs) was studied in mouse
      bleeding models. To explore their related hemostatic mechanism, coagulation
      parameters and platelets were measured. RESULTS: The PCC-CDs ranged in diameter
      from 1.2 to 4.8 nm and had a quantum yield of 9.62%. They exhibited no toxicity
      up to concentrations of 1000 MUg/ml. After administration, mice had a
      significantly shortened bleeding time and coagulation parameters and platelets
      significantly increased. CONCLUSION: These results showed the definite hemostatic
      effect of PCC-CDs.

PMID- 29338621
TI  - Assessing the acute effects of CDP-choline on sensory gating in schizophrenia: A
      pilot study.
AB  - Deficient sensory gating (SG) in schizophrenia is associated with functional
      outcome and offers a therapeutic target as it is linked to the altered
      function/expression of the alpha7 nicotinic acetylcholine receptors (nAChRs).
      This study analyzed the effects of citicoline (CDP-choline), a supplement with
      alpha7 nAChRs agonist properties, on SG in a sample of schizophrenia (SZ)
      patients. Using a randomized, placebo-controlled, double-blind design the dose
      dependent (500 mg, 1000 mg, 2000 mg) and baseline-dependent (deficient versus
      normal suppressors) effects of CDP-choline on SG were examined using the P50
      event-related potential (ERP) index of SG. Overall analysis failed to demonstrate
      treatment effects but CDP-choline improved SG (500 mg) in the deficient SZ
      subgroup by increasing suppression of the S2 P50 amplitude. These findings
      tentatively support alpha7 nAChR dysfunction in the expression of SG deficits and
      suggest further trials to assess the effects of sustained alpha7 nAChR activation
      on SG with low doses of CDP-choline.

PMID- 29338622
TI  - Grief and coping of parents whose child has a constant life-threatening
      disability, hypoplastic left heart syndrome with reference to the Dual-Process
      Model.
AB  - This paper reports on a study that examined the grief and coping of 29 parents
      whose child has hypoplastic left heart syndrome using the Dual Process Model. The
      study employed a secondary thematic analysis of interviews at key times of
      treatment and recovery for the child. After the diagnosis, parents experienced
      intense loss (LO), but focused upon restoration-orientated tasks (RO) to support
      their child. Over time, most parents employed a healthy oscillation between LO
      coping and RO coping, with waves of grief and with some grieving suppressed.
      There are some specific grief and coping and gender patterns employed by parents.

PMID- 29338620
TI  - Diminished Dentate Gyrus Filtering of Cortical Input Leads to Enhanced Area Ca3
      Excitability after Mild Traumatic Brain Injury.
AB  - Mild traumatic brain injury (mTBI) disrupts hippocampal function and can lead to
      long-lasting episodic memory impairments. The encoding of episodic memories
      relies on spatial information processing within the hippocampus. As the primary
      entry point for spatial information into the hippocampus, the dentate gyrus is
      thought to function as a physiological gate, or filter, of afferent excitation
      before reaching downstream area Cornu Ammonis (CA3). Although injury has
      previously been shown to alter dentate gyrus network excitability, it is unknown
      whether mTBI affects dentate gyrus output to area CA3. In this study, we assessed
      hippocampal function, specifically the interaction between the dentate gyrus and
      CA3, using behavioral and electrophysiological techniques in ex vivo brain slices
      1 week following mild lateral fluid percussion injury (LFPI). Behaviorally, LFPI
      mice were found to be impaired in an object-place recognition task, indicating
      that spatial information processing in the hippocampus is disrupted.
      Extracellular recordings and voltage-sensitive dye imaging demonstrated that
      perforant path activation leads to the aberrant spread of excitation from the
      dentate gyrus into area CA3 along the mossy fiber pathway. These results suggest
      that after mTBI, the dentate gyrus has a diminished capacity to regulate cortical
      input into the hippocampus, leading to increased CA3 network excitability. The
      loss of the dentate filtering efficacy reveals a potential mechanism by which
      hippocampal-dependent spatial information processing is disrupted, and may
      contribute to memory dysfunction after mTBI.

PMID- 29338623
TI  - Diabetic Peripheral Neuropathic Pain From the Perspective of Turkish Patients: A
      Qualitative Study.
AB  - INTRODUCTION: Diabetic peripheral neuropathy (DPN) affects almost 30% to 50% of
      patients with diabetes, 40% to 60% of whom suffer from diabetic peripheral
      neuropathic pain (DPNP). Few studies have focused on individual experiences of
      DPNP in patients with diabetes. The purpose of this qualitative study was to
      elucidate the effects of DPNP on daily life and individual feelings regarding
      living with DPNP from the perspective of Turkish patients. METHOD: A total of 14
      patients were interviewed, and interpretative phenomenological analysis was used
      to identify themes. RESULTS: Findings indicated four main themes, including (a)
      physical limitations, (b) difficulties with daily routines, (c) social
      limitations, and (d) psychological impacts such as emotional changes, and being a
      burden on family. CONCLUSION: This study revealed that the majority of patients
      carry significant concerns about becoming a burden on their family and are afraid
      of becoming dependent on others because of DPNP. IMPLICATION FOR PRACTICE: For
      the effective management of DPNP, health professionals need to consider using a
      holistic approach to address difficulties in daily living such as physical
      limitations and sexual problems.

PMID- 29338624
TI  - Use of Service Learning to Increase Master's-Level Nursing Students'
      Understanding of Social Determinants of Health and Health Disparities.
AB  - INTRODUCTION: It is important for graduate-level nursing students to be competent
      in the issues involved in the social determinants of health and health
      disparities and have the tools to address them as graduates. METHOD: As part of a
      nursing workforce diversity program, master's-level nursing students were
      required to participate in a service learning project exposing them to an issue
      not directly linked to health-long bus rides for students as a result of school
      consolidations-to achieve educational goals and objectives while providing a
      service to an advocacy agency. RESULTS: Eighteen students completed the project,
      providing the advocacy agency with firsthand accounts about the impact of long
      bus rides and in-depth reviews of literature on the topic and laws and
      regulations of other states. CONCLUSION: These results further support providing
      nursing students opportunities to fully engage with multicultural communities to
      gain a broader understanding of health disparities and social determinants of
      health.

PMID- 29338626
TI  - Fitts' Law is Applicable to Trunk Coordination Measurements in a Sitting
      Position.
AB  - Trunk coordination is essential for many activities of daily living in wheelchair
      users. This study investigated whether Fitts' law is applicable to trunk
      movements in a sitting position. Fourteen healthy adults performed two series of
      24 tasks of trunk flexion-extension movements in a sitting position. The results
      showed significant linear relationships between average group movement time (MT)
      and index of difficulty (ID) over all tasks (r2 = 0.92) and within target
      distances (0.94 < r2 < 1.00). Target distance affected intercept and slope (P <
      0.001). Hence, Fitts' law is applicable to the studied trunk movements in a
      sitting position, indicating these trunk movements tasks could serve as a basis
      for qualitative trunk coordination tests. Transferability of these conclusions to
      wheelchair users, and optimal test design should be further investigated.

PMID- 29338625
TI  - Delivery of chemotherapeutics using spheres made of bioengineered spider silks
      derived from MaSp1 and MaSp2 proteins.
AB  - AIM: Analysis of the properties and chemotherapeutics delivery potential of
      spheres made of bioengineered spider silks MS1 and MS2. MATERIALS & METHODS: MS1
      and MS2 derived from Nephila clavipes dragline silks - MaSp1 and MaSp2,
      respectively - formed spheres that were compared in terms of physicochemical
      properties, cytotoxicity and loading/release of chemotherapeutics. RESULTS: MS2
      spheres were more dispersed, smaller, of solid core, of higher beta-sheet
      structure content, and of opposite (negative) charge than MS1 spheres. Preloaded
      MS2 showed greater applicability for mitoxantrone, while postloaded for etoposide
      delivery compared with MS1 spheres. However, MS1 spheres were a better choice for
      doxorubicin delivery than MS2. CONCLUSION: Bioengineered silks can be tailored to
      develop a system with optimal drug loading and release properties.

PMID- 29338627
TI  - ?

PMID- 29338628
TI  - ?

PMID- 29338629
TI  - [CME Answers: "Lumbar Spinal Canal Stenosis" from PRAXIS No. 01].

PMID- 29338630
TI  - [CME: Post-Cardiac Injury Syndrome - a Special Form of Acute Pericarditis.]

PMID- 29338631
TI  - ?

PMID- 29338632
TI  - ?

PMID- 29338633
TI  - ?

PMID- 29338634
TI  - ?

PMID- 29338635
TI  - ?

PMID- 29338636
TI  - ?

PMID- 29338637
TI  - Selected plant essential oils and their main active components, a promising
      approach to inhibit aflatoxigenic fungi and aflatoxin production in food.
AB  - Recent research has showed that Aspergillus flavus and Aspergillus parasiticus
      are aflatoxigenic species that can become very competitive in the framework of
      climate change. Aflatoxins show carcinogenic, mutagenic, immunotoxic and
      teratogenic effects on human and animals. Effective and sustainable measures to
      inhibit these species and aflatoxins in food are required. Origanum vulgare and
      Cinnamomum zeylanicum essential oils (EOs) and their major active constituents,
      carvacrol and cinnamaldehyde, respectively, were assayed for inhibiting these
      species and aflatoxin production in maize extract medium under different
      environmental conditions. Doses of 10-1000 mg l-1 were assayed and the effective
      doses for 50 (ED50) and 90% (ED90) growth inhibition were determined. The ED50 of
      cinnamaldehyde, carvacrol, oregano EO, and cinnamon EO against A. flavus were in
      the ranges 49-52.6, 98-145, 152-505, 295-560 mg l-1 and against A. parasiticus in
      the ranges 46-55.5, 101-175, 260-425 and 490-675 mg l-1, respectively, depending
      on environmental conditions. In A. flavus treatments ED90 were in the ranges 89.7
      90.5, 770-860 and 820->1000 mg l-1 for cinnamaldehyde, carvacrol and cinnamon EO,
      and in A. parasiticus treatments in the ranges 89-91, 855->1000 and 900->1000 mg
      l-1, respectively. ED90 values for oregano EO against both species were >1000 mg
      l-1. Growth rates of both species were higher at 37 than at 25 degrees C and at
      0.99 than at 0.96 aw. Aflatoxin production was higher at 25 than at 37 degrees C.
      Stimulation of aflatoxin production was observed at low doses except for
      cinnamaldehyde treatments. The effectiveness of EOs and their main constituents
      to inhibit fungal growth and aflatoxin production in contact assays was lower
      than in vapour phase assays using bioactive EVOH-EO films previously reported.

PMID- 29338638
TI  - Frequency-dependence of discomfort caused by vibration and mechanical shocks.
AB  - The frequency content of a mechanical shock is not confined to its fundamental
      frequency, so it was hypothesised that the frequency-dependence of discomfort
      caused by shocks with defined fundamental frequencies will differ from the
      frequency-dependence of sinusoidal vibration. Subjects experienced vertical
      vibration and vertical shocks with fundamental frequencies from 0.5 to 16 Hz and
      magnitudes from +/-0.7 to +/-9.5 ms-2. The rate of growth of discomfort with
      increasing magnitude of motion decreased with increasing frequency of both
      motions, so the frequency-dependence of discomfort varied with the magnitudes of
      both motions and no single frequency weighting will be ideal for all magnitudes.
      At the frequencies of sinusoidal vibration producing greatest discomfort (4-16
      Hz), shocks produced less discomfort than vibration with same peak acceleration
      or unweighted vibration dose value. Frequency-weighted vibration dose values
      provided the best predictions of the discomfort caused by different frequencies
      and magnitudes of vibration and shock. Practitioner Summary: Human responses to
      vibration and shock vary according to the frequency content of the motion. The
      ideal frequency weighting depends on the magnitude of the motion. Standardised
      frequency-weighted vibration dose values estimate discomfort caused by vibration
      and shock but for motions containing very low frequencies the filtering is not
      optimum.

PMID- 29338639
TI  - Is Continuous Passive Motion Effective in Patients with Lymphedema? A Randomized
      Controlled Trial.
AB  - BACKGROUND: In this randomized controlled study, we aimed to evaluate the effect
      of shoulder flexion exercise using continuous passive motion (CPM) on lymphedema
      during the treatment of breast cancer-related lymphedema (BCRL). METHODS: Thirty
      patients with BCRL were enrolled and completed the study. Fourteen patients were
      treated with complete decongestive therapy (CDT) and CPM in the intervention
      group, and 16 patients were treated with CDT alone (control group) for 15
      sessions. The main outcome measures were included; the shoulder range of motion
      (ROM) assessed with a goniometer, limb volume difference measured using the water
      immersion method, function with the Disabilities of the Arm, Shoulder and Hand
      (DASH), and the quality of life using the Functional Assessment of Cancer Therapy
      for Breast Cancer (FACT-B4). Lymphedema volume measures were taken at baseline,
      on days 1, 2, 3, 4, 5, 10, and 15; and shoulder ROM, FACT-B4, and DASH were taken
      at baseline and on day 15. RESULTS: All subjects were similar at baseline. After
      treatment significant improvement was found in ROM, volumetric differences, DASH,
      and FACT-B4 scores in both groups. No significant differences were observed in
      the volumetric differences, ROM, and the DASH, and FACT-B4 scores between the
      groups, except for the FACT-B4 physical well-being subscores, which were better
      in intervention group. CONCLUSION: Our study results showed that CPM did not
      contribute to the reduction of BCRL.

PMID- 29338640
TI  - New molecular features of cowpea bean (Vigna unguiculata, l. Walp) beta-vignin.
AB  - Cowpea seed beta-vignin, a vicilin-like globulin, proved to exert various health
      favourable effects, including blood cholesterol reduction in animal models. The
      need of a simple scalable enrichment procedure for further studies for tailored
      applications of this seed protein is crucial. A chromatography-independent
      fractionation method allowing to obtain a protein preparation with a high degree
      of homogeneity was used. Further purification was pursued to deep the molecular
      characterisation of beta-vignin. The results showed: (i) differing glycosylation
      patterns of the two constituent polypeptides, in agreement with amino acid
      sequence features; (ii) the seed accumulation of a gene product never identified
      before; (iii) metal binding capacity of native protein, a property observed only
      in few other legume seed vicilins.

PMID- 29338641
TI  - An assessment of the level of awareness and reported complaints regarding
      occupational health hazards and the utilization of personal protective equipments
      among the welders of Lahore, Pakistan.
AB  - Objective To assess the level of awareness and reported complaints of
      occupational health hazards among the welders of Lahore. Methods A cross
      sectional descriptive study of 70 welders. An interview questionnaire was
      employed to assess awareness and complaints, the possession and utilization of
      protective personal equipment (PPE), and socio-demographic characteristics.
      Results All of the respondents were male with a mean age of 25.7 years. 54.3% of
      the respondents were aware of welding as a risk to their health. 98.6% possessed
      at least 1 PPE. There was an association between the level of education and the
      awareness of a health risk (chi2 = 6.885; p = 0.032). The most frequent complaint
      was foreign body in the eye (47.1%) followed by arc eye injury (45.7%), cuts and
      injuries (50.0%), and burns (48.6%). Conclusion The findings suggest that welders
      had low level of awareness and reported many complaints of occupational health
      hazards. Preventive initiatives are recommended.

PMID- 29338642
TI  - Functional evolution of biosynthetic enzymes that produce plant volatiles.
AB  - Plants synthesize volatile compounds to attract pollinators. The volatiles
      emitted by flowers are often complex mixtures of organic compounds; pollinators
      are capable of distinctly recognizing different volatile compounds. Plants also
      produce volatile compounds to protect themselves against herbivores and
      pathogens. Some of the volatile compounds produced in floral and vegetative
      tissues are toxic to insects and microbes. To adapt changes in the environment,
      plants have evolved the ability to synthesize a unique set of volatiles.
      Intensive studies have identified and characterized the enzymes responsible for
      the formation of plant volatiles. In particular, many biosynthetic genes have
      been isolated and their enzymatic functions have been proposed. This review
      describes how plants have evolved the biosynthetic pathways leading to the
      formation of green leaf volatiles and phenylpropene volatiles.

PMID- 29338643
TI  - High School Coaches' Experiences With Openly Lesbian, Gay, and Bisexual Athletes.
AB  - Despite reports that there has been a positive trend in perception and treatment
      of lesbian, gay, and bisexual (LGB) individuals in recent years (Griffin, 2012 ;
      Loftus, 2001 ), sport, in general, is still an uncertain, and sometimes even
      hostile, environment for LGB athletes (Anderson, 2005 ; Waldron & Krane, 2005 ).
      To gain more information on coach understanding and perceptions of the team
      environment, 10 high school head coaches in the United States were interviewed to
      explore their experiences coaching openly LGB athletes. Qualitative analyses
      revealed four primary themes associated with coach experiences: team environment
      dogmas and observations, fundamental beliefs contributing to perceptions of LGB
      athletes, types and timing of sexual orientation disclosure, and differential LGB
      athlete characteristics. Future research should examine these primary themes in
      more detail through interviews with LGB athletes, as well as high school coaches
      in more traditionally masculine sports, such as football, men's basketball, and
      wrestling.

PMID- 29338644
TI  - Pulmonary mucoepidermoid carcinoma: diagnosis and treatment.
AB  - INTRODUCTION: Primary mucoepidermoid carcinomas (MEC) of the lung are rare and
      represent a diagnostic challenge. MEC in the lung is under the umbrella of
      primary salivary gland type tumors of the lung. Areas covered: In general,
      salivary gland type tumors are represented by malignant neoplasms that may range
      from low to intermediate to high-grade type of malignancy sharing similar
      histopathological features as those in salivary glands. The focus in this review
      will be on one tumor in particular - mucoepidermoid carcinoma. Clinical,
      radiological, histopathological, and molecular diagnostic features will be
      highlighted in order to provide an insight on this unusual tumor in the lung. In
      addition, the treatment of these tumors will be discussed. Expert commentary: It
      is important to stress that in the majority of cases, the proper use of
      histopathological assessment is the most important step in arriving at an
      accurate diagnosis. It is also important to recognized that there are other
      unusual primary tumoral conditions of the lung, which may pose a significant
      challenge in the differential diagnosis. The importance of proper recognition of
      mucoepidermoid carcinoma and its grading will be highlighted in order to assess
      clinical outcome.

PMID- 29338645
TI  - Remote Iliac Artery Endarterectomy: A Case Series and Systematic Review.
AB  - PURPOSE: To evaluate the long-term results of remote iliac artery endarterectomy
      (RIAE) in 2 vascular referral centers and review existing literature. METHODS: A
      retrospective analysis was conducted of 109 consecutive patients (mean age 64.2+/
      10.7 years; 72 men) who underwent 113 RIAE procedures for lower limb ischemia
      from January 2004 to August 2015 at 2 vascular centers. The majority of limbs
      (82, 72.6%) had TASC II D lesions (31 TASC II C). Primary outcome measures were
      primary, assisted primary, and secondary patency. A comprehensive literature
      search was performed in the PubMed and EMBASE databases to identify all English
      language studies published after 1990 reporting the results of RIAE. RESULTS:
      Technical success was achieved in 95 (84.1%) of the 113 procedures. The
      complication rate was 13.7%, and 30-day mortality was 0%. At 5 years, primary
      patency was 78.2%, assisted primary patency was 83.4%, and secondary patency was
      86.7%. Hemodynamic success was obtained in 91.7% of patients, and clinical
      improvement was observed in 95.2%. Freedom from major amputation was 94.7% at 5
      years. The systematic review comprised 6 studies including 419 RIAEs, and pooled
      data showed results similar to the current study. CONCLUSION: For external iliac
      artery occlusions extending into the common femoral artery, RIAE appears to be a
      valuable hybrid treatment option. It combines acceptable morbidity and low
      mortality with good long-term patency. It has some advantages over an open
      surgical iliofemoral bypass or complete endovascular revascularization and could
      be the best treatment option in selected cases.

PMID- 29338646
TI  - Cognitive determinants of cervical cancer screening behavior among housewife
      women in Iran: An application of Health Belief Model.
AB  - Our aim in this cross-sectional study was to assess the cognitive determinants of
      Cervical Cancer Screening Behavior (CCSB) among housewife women in Islamabad
      County, Iran. Through multistage random sampling we recruited and interviewed 280
      housewife women. The women who perceived more benefits of performing the Pap test
      (OR = 1.11), and perceived fewer barriers (OR = 0.915), and higher self-efficacy
      to perform the test (OR = 1.12) were more likely to have a CCSB in the previous
      three years. Our findings are informative for the development of targeted
      interventions to foster CCSB among housewife women.

PMID- 29338650
TI  - Stoicism and Alchemy in Late Antiquity: Zosimus and the Concept of Pneuma.
AB  - At the beginning of the twentieth century, historians associated the alchemy of
      the third-century alchemist Zosimus of Panopolis with Platonism and
      Aristotelianism, explicating his theory of alchemical transmutation under the
      intellectual umbrella of these philosophical traditions. More recently, scholars
      of alchemy such as Christina Viano and William Newman have suggested a connection
      between Zosimean alchemy and Stoicism. Through a close reading of texts in
      Zosimus's corpus, this paper posits a Stoic interpretation of several aspects of
      Zosimean alchemy, focusing on the concepts of pneuma and tension. For Zosimus, I
      argue, pneuma played a vital role in colouring metals, while tension conferred
      stability and cohesion upon metallic compounds. This interpretation suggests that
      Zosimus applied Stoic concepts to describe the alchemical process of tincturing
      metals.

PMID- 29338653
TI  - A New Alchemical Poem Attributed to Khalid b. Yazid (d. ca. 705).
AB  - This paper deals primarily with the identification of an inaccurately catalogued
      alchemical poem attributed to the famous Umayyad prince Khalid b. Yazid (d. 705),
      edited, translated, and commented upon here for the first time. The paper also
      addresses the authenticity of Khalid's interest in alchemy and connects that
      interest to the need of the early Islamic empire to develop its own gold coinage
      as a sign of political independence from Byzantine coinage that was up till then
      the currency of the lands occupied by early Muslims in the regions of modern-day
      Egypt and Syria. On the matter of the legendry character of Khalid which was
      apparently started by Ibn Khaldun and passed on after him to most nineteenth
      century and early twentieth-century orientalists, the paper exposes here the
      inner contradictions in Ibn Khaldun's theorising on the matter, and his failure
      to understand why someone like the historical Prince Khalid would be interested
      in alchemy.

PMID- 29338655
TI  - The Alchemical Manuscripts of David Lindsay (1587-1641), Lord Lindsay of
      Balcarres.
AB  - The private book collection of David Lindsay, First Lord Lindsay of Balcarres
      (1587-1641), was one of the largest in early modern Scotland. Despite being
      dispersed during the following three centuries, this collection still provides
      evidence for Lindsay's scientific interests and approach to the study of alchemy.
      In this paper we seek to partially reconstruct his library by describing and,
      where possible, identifying the sources of Lindsay's own transcriptions of
      alchemical texts, as well as works mentioned in a book-list written in his hand.
      We conclude that Lindsay was not just an important early modern collector, but
      also a careful reader, part of an extensive network of contacts with whom he
      exchanged books and information.

PMID- 29338658
TI  - The Chemical Club: An Early Nineteenth-Century Scientific Dining Club.
AB  - The Chemical Club (fl. 1806-1828) was a small scientific dining club in London.
      Among its members were Sir Humphry Davy, William Hyde Wollaston, and Alexander
      Marcet. Other accomplished men of science, including John Dalton, Jons Jacob
      Berzelius, and Augustin Pyramus de Candolle, also attended its meetings as
      guests. This article, drawing on the unpublished papers of Lionel Felix Gilbert,
      as well as a range of contemporary sources in print and manuscript, presents the
      first substantial history of the Chemical Club, and situates it in the context of
      the scientific and social networks of the period. It aims to enrich our
      understanding of the scientific culture of the early nineteenth century in
      Britain by tracing the Club's influence on, or connection to, some of the most
      pioneering and transformative scientific work of the first quarter of the 1800s,
      such as the discovery of nitrogen trichloride, the invention of the miners'
      safety lamp, and Hans Christian Orsted's work on electromagnetism.

PMID- 29338659
TI  - Enfranchising grief following suicide: A case study of an Israeli social
      organization.
AB  - Researchers have yet to explore suicide survivors activities in social
      organizations, which was the present purpose. I studied an Israeli organization,
      Path to Life, by interviewing 16 members, attending 11 events, and examining
      media, online, and print information. Although mainly comprised of activists
      whose loss occurred in civilian circumstances, frame analysis revealed that the
      organization emphasizes connections between suicide and esteemed military-related
      death. By relying on a legitimate model of dealing with death, the activists
      provided meaning to suicide and promoted a sociocultural change through drawing
      attention to a silenced death, upgrading the suicide victims' status, and
      enfranchising survivors' grief.

PMID- 29338661
TI  - Collaborative Processes of Developing A Health Literacy Toolkit: A Case from
      Fukushima after the Nuclear Accident.
AB  - Following the Fukushima nuclear accident in 2011, the central government provided
      health and radiation-related information that was incomplete, difficult to
      understand and contradictory, leading to widespread distrust in the community.
      Thus, from 2013 to 2014, we developed and implemented a series of health literacy
      training workshops for local public health nurses, often the first health care
      professionals with whom members of the community interact. The results from our
      program evaluation revealed that the task of paraphrasing professional terms and
      skills related to relaying numeric information to the community were difficult
      for the nurses to acquire. In 2016, to further support the communication efforts
      of public health nurses, we developed a pocket-size "health literacy toolkit"
      that contained a glossary explaining radiation-related terms in plain language
      and an index to measure the accessibility of both text and numerical information,
      so that nurses could calibrate and appreciate the literacy demand of information.
      This case study documents an interprofessional collaborative effort for the
      development of the toolkit, and highlights the iterative process of building
      health literacy skills in health care professionals.

PMID- 29338660
TI  - Social-ecological factors associated with selling sex among men who have sex with
      men in Jamaica: results from a cross-sectional tablet-based survey.
AB  - BACKGROUND: Globally, men who have sex with men (MSM) experience social
      marginalization and criminalization that increase HIV vulnerability by
      constraining access to HIV prevention and care. People who sell sex also
      experience criminalization, rights violations, and violence, which elevate HIV
      exposure. MSM who sell sex may experience intersectional stigma and intensified
      social marginalization, yet have largely been overlooked in epidemiological and
      social HIV research. In Jamaica, where same sex practices and sex work are
      criminalized, scant research has investigated sex selling among MSM, including
      associations with HIV vulnerability. OBJECTIVE: We aimed to examine social
      ecological factors associated with selling sex among MSM in Jamaica, including
      exchanging sex for money, shelter, food, transportation, or drugs/alcohol (past
      12 months). METHODS: We conducted a cross-sectional survey with a peer-driven
      sample of MSM in Kingston, Ocho Rios, and Montego Bay. Multivariable logistic
      regression analyses were conducted to estimate intrapersonal/individual,
      interpersonal/social, and structural factors associated with selling sex.
      RESULTS: Among 556 MSM, one-third (n = 182; 32.7%) reported selling sex. In the
      final multivariable model, correlates of selling sex included:
      individual/intrapersonal (lower safer sex self-efficacy [AOR: 0.85, 95% CI: 0.77,
      0.94]), interpersonal/social (concurrent partnerships [AOR: 5.52, 95% CI: 1.56,
      19.53], a higher need for social support [AOR: 1.08, 95% CI: 1.03, 1.12],
      lifetime forced sex [AOR: 2.74, 95% 1.65, 4.55]) and structural-level factors
      (sexual stigma [AOR: 1.09, 95% CI: 1.04, 1.15], food insecurity [AOR: 2.38, 95%
      CI: 1.41, 4.02], housing insecurity [AOR: 1.94, 95% CI: 1.16, 3.26], no regular
      healthcare provider [AOR: 2.72, 95% CI: 1.60, 4.64]). CONCLUSIONS: This study
      highlights social ecological correlates of selling sex among MSM in Jamaica, in
      particular elevated stigma and economic insecurity. Findings suggest that MSM in
      Jamaica who sell sex experience intensified social and structural HIV
      vulnerabilities that should be addressed in multi-level interventions to promote
      health and human rights.

PMID- 29338662
TI  - Legal barriers to access abortion services through a human rights lens: the
      Uruguayan experience.
AB  - Sexual and reproductive health (SRH) has increasingly gained importance in the
      field of international human rights law. The work of the United Nations (UN)
      bodies, in particular the recently adopted General Comment 22 (GC 22), has been
      instrumental in signalling the importance of the SRH legal framework and in
      setting clear guidelines to steer countries into enacting/modifying/repealing
      national laws in order to comply with their international obligations vis-a-vis
      SRH. Although within the region Uruguay is regarded as a pioneer in terms of
      women's status and rights, including sexual and reproductive health and rights,
      evidence points to a number of challenges. This article explores the extent to
      which the Uruguayan abortion law complies with the country's international human
      rights obligations as conceptualised by GC 22. It uses the Uruguayan abortion
      law, its regulatory decree, and the highest administrative court's decision in
      Alonso et al v. Poder Ejecutivo as the main pivots for the discussion. The
      results reveal that - in spite of the praise it receives at the international
      level and the adoption of a less restrictive abortion law - Uruguay has fallen
      short in adopting a legal framework that complies with the international
      standards and guarantees effective access to abortion services.

PMID- 29338663
TI  - Cultural Competency in Dementia Care: An African American Case Study.
AB  - Age is the greatest risk factor for Alzheimer's disease, the most common cause of
      dementia. The older population in the United States is growing, and within this
      demographic ethnic and racial diversity is also on the rise. This article
      introduces Stanford Health Care's Memory Support Program (MSP) as a model for
      culturally competent dementia care that spans inpatient and outpatient settings.
      The case study of an African American patient and family dealing with an
      Alzheimer's disease diagnosis and comorbid conditions is presented and explored
      to illustrate the MSP model. The authors make recommendations for the
      implementation of similar continuum of care services in other institutions. As
      research continues to show, the cultural competence of medical professionals can
      impact patient quality of care and health outcomes. More research is needed to
      appropriately support positive outcomes for patients and families of diverse
      ethnic and racial backgrounds.

PMID- 29338664
TI  - Qualitative analysis and conceptual mapping of patient experiences in home health
      care.
AB  - This study explored patient experiences in home health care through a literature
      review, focus groups, and interviews. Our goal was to develop a conceptual map of
      home health care patient experience domains. The conceptual map identifies
      technical and personal spheres of care, relating prior studies to new focus group
      and interview findings and identifying the most important domains of care. Study
      participants (n = 35) most frequently reported the most important domain as staff
      who are caring, supportive, patient, empathetic, respectful, and considerate
      (endorsed by 29% of participants). The conceptual map includes 114 discrete
      domains.

PMID- 29338665
TI  - Adjuvant radiotherapy in patients with diffuse large B-cell lymphoma in advanced
      stage (III/IV) improves the outcome in the rituximab era.
AB  - OBJECTIVES: To assess the efficacy and toxicity of adjuvant radiotherapy (RT) in
      patients with diffuse large B-cell lymphoma (DLBCL) and nodal bulky disease, on
      complete response, after six cycles of RCHOP (rituximab, cyclophosphamide,
      doxorubicin, vincristine and prednisone), we began an open-label clinical trial
      in a large cohort with longer follow-up to evaluate the outcome measured from
      progression-free survival (PFS) and overall survival (OS). PATIENTS AND METHODS:
      Between 2006 and 2010, 258 consecutive patients with DLBCL and nodal bulky
      disease (tumor mass >10 cm) were randomly assigned to receive either RT (involved
      field, 30 Gy) (127 patients) or no (control group) (131 patients). RESULTS: The
      actuarial curves at 5 years of PFS were 87% (95% confidence interval (CI): 72
      97%) in the RT group, which was significantly different from the control group
      value of 45% (95% CI: 34-60%) (p < 0.001); also OS in the RT group was
      significantly better than that in the control group: 91% (95% CI: 84-99%) and 59%
      (95% CI: 52-66%), respectively (p < 0.001). RT was well tolerated, acute toxicity
      was mild and until now late toxicity did not appear. CONCLUSIONS: The use of
      adjuvant RT in patients with DLBCL and nodal bulky disease improves the outcome
      with PFS and OS, with minimal toxicity; thus, we felt that adjuvant RT will be
      considered as a part of the initial treatment in this setting of patients, even
      in the rituximab era.

PMID- 29338667
TI  - Docosahexaenoic acid prevents resistance to antiepileptic drugs in two animal
      models of drug-resistant epilepsy.
AB  - OBJECTIVES: One-third of epileptic patients are resistant to antiepileptic drugs.
      Few clinical studies with small sample size indicate that polyunsaturated fatty
      acids could control drug-resistant epilepsy. We examined the efficacy of acute
      and chronic administration of docosahexaenoic acid (DHA) in two animal models of
      drug-resistant epilepsies, i.e. 6-Hz psychomotor seizures in mice and lamotrigine
      (LTG)-resistant kindled rats. METHODS: Mice received a single injection of DHA
      (300 uM, i.c.v.) along with phenytoin (PHT) or LTG (i.p.). Six-Hz electroshock
      (0.2 milliseconds rectangular pulse width, 3 seconds duration, 44 mA current) was
      given 15 minutes after DHA, and seizure behaviors were recorded. In LTG-resistant
      kindled rats, a single dose of DHA (300 uM, i.c.v.) was administered with LTG,
      and seizure parameters were measured. In chronic treatment, mice received DHA
      (0.1 g/day, orally) for 30 days. Then, a single dose of LTG or PHT was
      administered to mice and 6-Hz-induced seizures were recorded. In rats, DHA (1 uM,
      i.c.v.) was administered during kindling development and effect of LTG in DHA
      pretreated LTG-resistant kindled rats was verified. RESULTS: LTG and PHT did not
      inhibit 6-Hz seizures in mice after single injection of DHA. However, LTG and PHT
      inhibited 6-Hz seizures in mice that received DHA for 1 month. Acute or chronic
      administration of DHA to LTG-resistant kindled rats led to the suppression of
      kindled seizure parameters by LTG. DISCUSSION: DHA removes the 'inherent
      resistance' of 6-Hz seizures to PHT and LTG, and prevents the development of
      pharmacodynamic tolerance to LTG in LTG-resistant kindled rats. DHA might have
      potential to be used as add-on therapy in patients with refractory epilepsy.

PMID- 29338666
TI  - Boosted TCA cycle enhances survival of zebrafish to Vibrio alginolyticus
      infection.
AB  - Vibrio alginolyticus is a waterborne pathogen that infects a wide variety of
      hosts including fish and human, and the outbreak of this pathogen can cause a
      huge economic loss in aquaculture. Thus, enhancing host's capability to survive
      from V. alginolyticus infection is key to fighting infection and this remains
      still unexplored. In the present study, we established a V. alginolyticus
      zebrafish interaction model by which we explored how zebrafish survived from V.
      alginolyticus infection. We used GC-MS based metabolomic approaches to
      characterize differential metabolomes between survival and dying zebrafish upon
      infection. Pattern recognition analysis identified the TCA cycle as the most
      impacted pathway. The metabolites in the TCA cycle were decreased in the dying
      host, whereas the metabolites were increased in the survival host. Furthermore,
      the enzymatic activities of the TCA cycle including pyruvate dehydrogenase (PDH),
      alpha-ketoglutaric dehydrogenase (KGDH) and succinate dehydrogenase (SDH) also
      supported this conclusion. Among the increased metabolites in the TCA cycle,
      malic acid was the most crucial biomarker for fish survival. Indeed, exogenous
      malate promoted zebrafish survival in a dose-dependent manner. The corresponding
      activities of KGDH and SDH were also increased. These results indicate that the
      TCA cycle is a key pathway responsible for the survival or death in response to
      infection caused by V. alginolyticus, and highlight the way on development of
      metabolic modulation to control the infection.

PMID- 29338668
TI  - Simultaneous determination of afidopyropen and its metabolite in vegetables,
      fruit and soil using UHPLC-MS/MS.
AB  - A new analytical method using the quick, easy, cheap, effective, rugged and safe
      (QuEChERS) procedure for simultaneous determination of afidopyropen and its
      metabolite M440I007 residues in tomato, watermelon, pepper, cucumber, pear,
      grape, cabbage and soil samples was developed using ultra-high performance liquid
      chromatography coupled with tandem mass spectrometry. The target compound was
      determined in less than 5.0 min using an electrospray ionisation source in
      positive mode (ESI+). The limit of quantification was 1 MUg kg-1 in different
      matrices. Two sorbents primary secondary amine and graphitised carbon black were
      used in the QuEChERS procedure, and matrix-matched standards gave satisfactory
      recoveries and relative standard deviation (RSD) values in different matrices at
      three spiked levels (1, 10 and 500 MUg kg-1). For afidopyropen, the recoveries
      ranged from 83% to 104% with an intra-day relative standard deviation (RSDr) of 1
      8%, while they were from 80% to 103% with RSDr of 2-8% for M440I007.
      Reproducibility ranged between 1% and 19% for the three spiked levels.

PMID- 29338669
TI  - Successful operative treatment of uterine leiomyoma with extensive intravenous
      extension to the IVC, right heart, and pulmonary arteries.
AB  - INTRODUCTION: Intravenous extension of benign uterine leiomyomata ('fibroids'),
      in the absence of discrete metastatic disease has rarely been reported.
      'Fibroids' remain one of the most common premenopausal uterine pathologies.
      METHODS AND RESULTS: We report the diagnosis and multidisciplinary led operative
      management of a 52-year-old woman with a histologically benign, but biologically
      aggressive, uterine leiomyoma with intravenous extension to the inferior vena
      cava (IVC), right heart and pulmonary arteries. CONCLUSIONS: Total abdominal
      hysterectomy and bilateral salpingo-oophorectomy combined with exploration of the
      sub-hepatic IVC and heart under deep hypothermic circulatory arrest achieved its
      successful macroscopic clearance.

PMID- 29338670
TI  - Vitamin A and vitamin D deficiencies exacerbate symptoms in children with autism
      spectrum disorders.
AB  - OBJECTIVES: This study was designed to investigate the vitamin A (VA) and vitamin
      D (VD) levels in children with autism spectrum disorders (ASD) and to determine
      whether co-deficiency of VA and VD exacerbates clinical symptoms in autistic
      children. METHODS: The Autism Behavior Checklist, Childhood Autism Rating Scale
      (CARS), and Social Responsiveness Scale (SRS) were used to assess the symptoms of
      332 children diagnosed as ASD. And the Gesell Developmental Scale (GDS) was used
      to evaluate neurodevelopment in children with ASD. Anthropometric measurement and
      questionnaire results were compared for all autistic children and 197 age- and
      gender-matched control children. Serum retinol levels were detected with high
      performance liquid chromatography, and serum levels of 25-OH vitamin D were
      measured with an immunoassay method in the two groups. RESULTS: The ZHA, ZWA, and
      ZBMIA of the children with ASD were significantly lower than those of the control
      children. Furthermore, higher proportions of children with picky eating,
      resistance to new foods, and eating problems were observed in the ASD group when
      compared with the control group. Serum retinol and 25-OH vitamin D levels in
      autistic children were significantly lower than those in the control children.
      Additionally, VA and VD co-deficiency impacts more on the symptoms and
      development in autistic children. CONCLUSIONS: We found that children with autism
      have more VA and VD deficiencies than control children, and VA and VD co
      deficiency may exacerbate the symptoms of children with ASD.

PMID- 29338671
TI  - Journal of Correctional Health Care.

PMID- 29338673
TI  - Editor's Letter.

PMID- 29338674
TI  - Would you be willing to zap your child's brain? Public perspectives on parental
      responsibilities and the ethics of enhancing children with transcranial direct
      current stimulation.
AB  - BACKGROUND: Transcranial direct current stimulation (tDCS) is an experimental
      brain stimulation technology that may one day be used to enhance the cognitive
      capacities of children. Discussion about the ethical issues that this would raise
      has rarely moved beyond expert circles. However, the opinions of the wider public
      can lead to more democratic policy decisions and broaden academic discussion of
      this issue. METHODS: We performed a quantitative survey of members of the U.S.
      public. A between-subjects design was employed, where conditions varied based on
      the trait respondents considered for enhancement. RESULTS: There were 227
      responses included for analysis. Our key finding was that the majority were
      unwilling to enhance their child with tDCS. Respondents were most reluctant to
      enhance traits considered fundamental to the self (such as motivation and
      empathy). However, many respondents may give in to implicit coercion to enhance
      their child in spite of an initial reluctance. A ban on tDCS was not supported if
      it were to be used safely for the enhancement of mood or mathematical ability.
      Opposition to such a ban may be related to the belief that tDCS use would not
      represent cheating or violate authenticity (as it relates to achievements rather
      than identity). CONCLUSIONS: The wider public appears to think that crossing the
      line from treatment to enhancement with tDCS would not be in a child's best
      interests. However, an important alternative interpretation of our results is
      that lay people may be willing to use enhancers that matched their preference for
      "natural" enhancers. A ban on the safe use of tDCS for enhancing nonfundamental
      traits would be unlikely to garner public support. Nonetheless, it could become
      important to regulate tDCS in order to prevent misuse on children, because
      individuals reluctant to enhance may be likely to give in to implicit coercion to
      enhance their child.

PMID- 29338675
TI  - Exploration into best practices in peer support for bereaved survivors.
AB  - This exploratory, qualitative study addresses the question: what are the
      important elements in effective peer support programs for bereaved survivors?
      Interviews with 10 highly experienced experts were analyzed to identify recurrent
      themes and elements. Findings indicate that effective peer support programs for
      the bereaved should be: easily accessible; confidential; provide a safe
      environment; use peer supporters with similar shared experiences to clients;
      select peer supporters carefully; partner with professional mental health
      providers; train peer supporters thoroughly; and provide care and monitoring for
      peer supporters. These results can help inform efforts to improve peer support
      programs for bereaved survivors.

PMID- 29338676
TI  - Finding the perfect sclerosant - Is it possible?

PMID- 29338677
TI  - Vitamin B-6 and depressive symptomatology, over time, in older Latino adults.
AB  - BACKGROUND: Low vitamin B-6 status has been linked to depressive symptomatology.
      We examined the longitudinal association of vitamin B-6 status with depressive
      symptomatology across 3-time points over ~5-7 years in a cohort of older Hispanic
      adults. METHODS: We used two-level hierarchical linear regression models for
      continuous outcomes. Vitamin B-6 status was associated with depressive
      symptomatology across these time points. RESULTS: Plasma pyridoxyl-5-phosphate
      (PLP) concentration, a time-varying predictor, was significantly associated with
      depressive symptomatology. Study participants with PLP deficiency, vs. optimal
      PLP, had higher baseline depressive symptoms (Center for Epidemiologic Studies
      Depression Scale (CES-D) score of 22 +/- 14, vs. 20 +/- 13); this differential
      remained constant over time and persisted after controlling for age, sex,
      education, body mass index, smoking and alcohol use, other relevant nutritional
      factors, perceived stress, stressful life events, allostatic load, and use of
      antidepressant medication. However, PLP concentration was not associated with the
      rate of change in depressive symptomatology over time. CONCLUSIONS: Suboptimal
      plasma PLP is associated with higher depressive symptomatology in older Hispanic
      of Puerto Rican descent and this appears to persist over time. Our data suggest
      that identification and treatment of vitamin B-6 deficiency may be a useful
      preventive approach in this population.

PMID- 29338678
TI  - Supplementation with Curcuma longa reverses neurotoxic and behavioral damage in
      models of Alzheimer's disease: A systematic review.
AB  - BACKGROUND: The formation of senile plaques and neurofibrillary tangles of the
      tau protein are the main pathological mechanism of Alzheimer's disease (AD).
      Current therapies for AD offer discrete benefits to the clinical symptoms and do
      not prevent the continuing degeneration of neuronal cells. Therefore, novel
      therapeutic strategies have long been investigated, where curcumin (Curcuma
      longa) has shown some properties that can prevent the deleterious processes
      involved in neurodegenerative diseases. OBJECTIVE: The aim of the present work is
      to review studies that addressed the effects of curcumin in experimental models
      (in vivo and in vitro) for AD. METHOD: This study is a systematic review
      conducted between January and June 2017, in which a consultation of scientific
      articles from indexed periodicals was carried out in Science Direct, United
      States National Library of Medicine (PubMed), Cochrane Library and Scielo
      databases, using the following descriptors: "Curcuma longa", "Curcumin" and
      "Alzheimer's disease". RESULTS: A total of 32 studies were analyzed, which
      indicated that curcumin supplementation reverses neurotoxic and behavioral
      damages in both in vivo and in vitro models of AD. CONCLUSION: The administration
      of curcumin in experimental models seems to be a promising approach in AD, even
      though it is suggested that additional studies must be conducted using distinct
      doses and through other routes of administration.

PMID- 29338679
TI  - Therapeutic role of methotrexate in pediatric Crohn's disease.
AB  - The main role of therapy in Crohn's disease (CD) is to achieve long-term clinical
      remission, and to allow for normal growth and development of children. The
      immunomodulatory drugs used for the maintenance of remission in CD include
      thiopurines (azathioprine and 6-mercaptopurine) and methotrexate (MTX).
      Development of hepatosplenic T-cell lymphoma in some patients with inflammatory
      bowel disease, treated with thiopurines only or in combination with anti-tumor
      necrosis factor agents, resulted in a growing interest in the therapeutic
      application of MTX in children suffering from CD. This review summarizes the
      literature on the therapeutic role of MTX in children with CD. MTX is often
      administered as a second-line immunomodulator, and 1-year clinical remission was
      reported in 25-69% of children with CD after excluding for the use of
      thiopurines. Initial data on MTX effectiveness in mucosal healing, and as a first
      line immunomodulator in pediatric patients with CD, are promising. A definite
      conclusion, however, may only be made on the basis of additional research with a
      larger number of subjects.

PMID- 29338680
TI  - MicroRNA-466 (miR-466) functions as a tumor suppressor and prognostic factor in
      colorectal cancer (CRC).
AB  - MicroRNAs (miRNAs) have an important role in the regulation of tumor development
      and metastasis. In this study, we investigated the clinical and prognostic value
      as well as biological function of miR-466 in colorectal cancer (CRC). Tumor and
      adjacent healthy tissues were obtained from 100 patients diagnosed with CRC. miR
      466 expression was determined by quantitative reverse transcription polymerase
      chain reaction (qRT-PCR). mRNA and protein levels of cyclin D1, apoptosis
      regulator BAX (BAX), and matrix metalloproteinase-2 (MMP-2) were analyzed by qRT
      PCR and Western blot, respectively, in SW-620 CRC cells transfected with miR-466
      mimics or negative control miRNA. Effects of miR-466 on SW-620 cell
      proliferation, cell cycle and apoptosis, and invasion were investigated using CCK
      8 assay, flow cytometry and Transwell assay, respectively. miR-466 expression was
      significantly downregulated in tumor tissues compared to matched adjacent non
      tumor tissues. Low expression of miR-466 was significantly correlated with the
      tumor size, Tumor Node Metastasis stage, lymph node metastasis, and distant
      metastasis. The overall survival of CRC patients with low miR-466 expression was
      significantly shorter compared to high-miR-466 expression group (log-rank test: p
      = 0.0103). Multivariate analysis revealed that low miR-466 expression was
      associated with poor prognosis in CRC patients. The ectopic expression of miR-466
      suppressed cell proliferation and migration/invasion, as well as induced G0/G1
      arrest and apoptosis in SW-620 cells. Moreover, the ectopic expression of miR-466
      decreased the expression of cyclin D1 and MMP-2, but increased BAX expression in
      SW-620 cells. In conclusion, our findings demonstrated that miR-466 functions as
      a suppressor miRNA in CRC and may be used as a prognostic factor in these
      patients.

PMID- 29338681
TI  - The evolutionary process of mammalian sex determination genes focusing on
      marsupial SRYs.
AB  - BACKGROUND: Maleness in mammals is genetically determined by the Y chromosome. On
      the Y chromosome SRY is known as the mammalian male-determining gene. Both
      placental mammals (Eutheria) and marsupial mammals (Metatheria) have SRY genes.
      However, only eutherian SRY genes have been empirically examined by functional
      analyses, and the involvement of marsupial SRY in male gonad development remains
      speculative. RESULTS: In order to demonstrate that the marsupial SRY gene is
      similar to the eutherian SRY gene in function, we first examined the sequence
      differences between marsupial and eutherian SRY genes. Then, using a parsimony
      method, we identify 7 marsupial-specific ancestral substitutions, 13 eutherian
      specific ancestral substitutions, and 4 substitutions that occurred at the stem
      lineage of therian SRY genes. A literature search and molecular dynamics
      computational simulations support that the lineage-specific ancestral
      substitutions might be involved with the functional differentiation between
      marsupial and eutherian SRY genes. To address the function of the marsupial SRY
      gene in male determination, we performed luciferase assays on the testis enhancer
      of Sox9 core (TESCO) using the marsupial SRY. The functional assay shows that
      marsupial SRY gene can weakly up-regulate the luciferase expression via TESCO.
      CONCLUSIONS: Despite the sequence differences between the marsupial and eutherian
      SRY genes, our functional assay indicates that the marsupial SRY gene regulates
      SOX9 as a transcription factor in a similar way to the eutherian SRY gene. Our
      results suggest that SRY genes obtained the function of male determination in the
      common ancestor of Theria (placental mammals and marsupials). This suggests that
      the marsupial SRY gene has a function in male determination, but additional
      experiments are needed to be conclusive.

PMID- 29338682
TI  - Soybean MADS-box gene GmAGL1 promotes flowering via the photoperiod pathway.
AB  - BACKGROUND: The MADS-box transcription factors are an ancient family of genes
      that regulate numerous physiological and biochemical processes in plants and
      facilitate the development of floral organs. However, the functions of most of
      these transcription factors in soybean remain unknown. RESULTS: In this work, a
      MADS-box gene, GmAGL1, was overexpressed in soybean. Phenotypic analysis showed
      that GmAGL1 overexpression not only resulted in early maturation but also
      promoted flowering and affected petal development. Furthermore, the GmAGL1 was
      much more effective at promoting flowering under long-day conditions than under
      short-day conditions. Transcriptome sequencing analysis showed that before
      flowering, the photoperiod pathway photoreceptor CRY2 and several circadian
      rhythm genes, such as SPA1, were significantly down-regulated, while some other
      flowering-promoting circadian genes, such as GI and LHY, and downstream genes
      related to flower development, such as FT, LEAFY, SEP1, SEP3, FUL, and AP1, were
      up-regulated compared with the control. Other genes related to the flowering
      pathway were not noticeably affected. CONCLUSIONS: The findings reported herein
      indicate that GmAGL1 may promote flowering mainly through the photoperiod
      pathway. Interestingly, while overexpression of GmAGL1 promoted plant maturity,
      no reduction in seed production or oil and protein contents was observed.

PMID- 29338684
TI  - A simple prediction model to estimate obstructive coronary artery disease.
AB  - BACKGROUND: A simple noninvasive model to predict obstructive coronary artery
      disease (OCAD) may promote risk stratification and reduce the burden of coronary
      artery disease (CAD). This study aimed to develop pre-procedural, noninvasive
      prediction models that better estimate the probability of OCAD among patients
      with suspected CAD undergoing elective coronary angiography (CAG). METHODS: We
      included 1262 patients, who had reliable Framingham risk variable data, in a
      cohort without known CAD from a prospective registry of patients referred for
      elective CAG. We investigated pre-procedural OCAD (>=50% stenosis in at least one
      major coronary vessel based on CAG) predictors. RESULTS: A total of 945 (74.9%)
      participants had OCAD. The final modified Framingham scoring (MFS) model
      consisted of anemia, high-sensitivity C-reactive protein, left ventricular
      ejection fraction, and five Framingham factors (age, sex, total and high-density
      lipoprotein cholesterol, and hypertension). Bootstrap method (1000 times)
      revealed that the model demonstrated a good discriminative power (c statistic,
      0.729 +/- 0.0225; 95% CI, 0.69-0.77). MFS provided adequate goodness of fit (P =
      0.43) and showed better performance than Framingham score (c statistic, 0.703 vs.
      0.521; P < 0.001) in predicting OCAD, thereby identifying patients with high
      risks for OCAD (risk score >= 27) with >=70% predictive value in 68.8% of
      subjects (range, 37.2-87.3% for low [<=17] and very high [>=41] risk scores).
      CONCLUSION: Our data suggested that the simple MFS risk stratification tool,
      which is available in most primary-level clinics, showed good performance in
      estimating the probability of OCAD in relatively stable patients with suspected
      CAD; nevertheless, further validation is needed.

PMID- 29338685
TI  - Functional health state description and valuation by people aged 65 and over: a
      pilot study.
AB  - BACKGROUND: Assessing quality of life among the elderly is a complex and
      multifaceted issue. Elderly people might find valuing and describing their
      personal experience of quality of life (QoL) demanding and cumbersome. This study
      therefore sought to determine the feasibility of administering two questionnaires
      in two samples of elderly people. METHODS: A preference-based instrument (EQ-5D +
      C) and a currently achieved functioning questionnaire (CAF) were utilized. Two
      pilot studies were performed. The first was performed in South Africa (n = 30),
      designed to test whether elderly respondents could complete and understand the
      two questionnaires and also to indicate which valuation method, visual analogue
      scale or time trade off they preferred. A second pilot study was performed in the
      Netherlands (n = 30), designed to investigate the use of both questionnaires in
      determining quality of life and health state valuations in a Dutch sample of
      elderly. RESULTS: Seventy percent of the South African respondents indicated that
      they preferred the visual analogue scale (VAS) method, when compared to the time
      trade-off (TTO). In both the South African and the Dutch pilot studies, the
      respondents, with different dependency levels, were able to use both
      questionnaires to determine health state descriptions and valuations. When
      ranking the profiles from fewer to more problems, the EQ-5D + C exhibits a
      gradual downwards trend, with a maximum of 100 and minimum VAS value of 41. The
      CAF also exhibits a gradual downwards trend, with a maximum of 1.00 and minimum
      VAS value of 36. CONCLUSIONS: The results indicate that individuals from
      different parts of the world are able to complete, describe, and value the
      questionnaires. It is our recommendation that a comprehensive study should be
      done, which includes both the EQ-5D + C questionnaire and the CAF questionnaire,
      since the two questionnaires have proven to be feasible in providing information
      on quality of life and well-being of elderly people.

PMID- 29338683
TI  - Genomic repeats, misassembly and reannotation: a case study with long-read
      resequencing of Porphyromonas gingivalis reference strains.
AB  - BACKGROUND: Without knowledge of their genomic sequences, it is impossible to
      make functional models of the bacteria that make up human and animal microbiota.
      Unfortunately, the vast majority of publicly available genomes are only working
      drafts, an incompleteness that causes numerous problems and constitutes a major
      obstacle to genotypic and phenotypic interpretation. In this work, we began with
      an example from the class Bacteroidia in the phylum Bacteroidetes, which is
      preponderant among human orodigestive microbiota. We successfully identify the
      genetic loci responsible for assembly breaks and misassemblies and demonstrate
      the importance and usefulness of long-read sequencing and curated reannotation.
      RESULTS: We showed that the fragmentation in Bacteroidia draft genomes assembled
      from massively parallel sequencing linearly correlates with genomic repeats of
      the same or greater size than the reads. We also demonstrated that some of these
      repeats, especially the long ones, correspond to misassembled loci in three
      reference Porphyromonas gingivalis genomes marked as circularized (thus complete
      or finished). We prove that even at modest coverage (30X), long-read resequencing
      together with PCR contiguity verification (rrn operons and an integrative and
      conjugative element or ICE) can be used to identify and correct the wrongly
      combined or assembled regions. Finally, although time-consuming and labor
      intensive, consistent manual biocuration of three P. gingivalis strains allowed
      us to compare and correct the existing genomic annotations, resulting in a more
      accurate interpretation of the genomic differences among these strains.
      CONCLUSIONS: In this study, we demonstrate the usefulness and importance of long
      read sequencing in verifying published genomes (even when complete) and
      generating assemblies for new bacterial strains/species with high genomic
      plasticity. We also show that when combined with biological validation processes
      and diligent biocurated annotation, this strategy helps reduce the propagation of
      errors in shared databases, thus limiting false conclusions based on incomplete
      or misleading information.

PMID- 29338686
TI  - Correction to: Effectiveness and safety of vitamin K antagonists and new
      anticoagulants in the prevention of thromboembolism in atrial fibrillation in
      older adults - a systematic review of reviews and the development of
      recommendations to reduce inappropriate prescribing.
AB  - CORRECTION: After publication of the original article [1] it was found that
      author Marc Krause's name had been spelt incorrectly. In the original article it
      is presented as Mark Krause, rather than Marc Krause. The revised spelling has
      been included in the author list for this Correction.

PMID- 29338687
TI  - Use of easy measurable phenotypic traits as a complementary approach to evaluate
      the population structure and diversity in a high heterozygous panel of tetraploid
      clones and cultivars.
AB  - BACKGROUND: Diversity in crops is fundamental for plant breeding efforts. An
      accurate assessment of genetic diversity, using molecular markers, such as single
      nucleotide polymorphism (SNP), must be able to reveal the structure of the
      population under study. A characterization of population structure using easy
      measurable phenotypic traits could be a preliminary and low-cost approach to
      elucidate the genetic structure of a population. A potato population of 183
      genotypes was evaluated using 4859 high-quality SNPs and 19 phenotypic traits
      commonly recorded in potato breeding programs. A Bayesian approach, Minimum
      Spanning Tree (MST) and diversity estimator, as well as multivariate analysis
      based on phenotypic traits, were adopted to assess the population structure.
      RESULTS: Analysis based on molecular markers showed groups linked to the
      phylogenetic relationship among the germplasm as well as the link with the
      breeding program that provided the material. Diversity estimators consistently
      structured the population according to a priori group estimation. The phenotypic
      traits only discriminated main groups with contrasting characteristics, as
      different subspecies, ploidy level or membership in a breeding program, but were
      not able to discriminate within groups. A joint molecular and phenotypic
      characterization analysis discriminated groups based on phenotypic
      classification, taxonomic category, provenance source of genotypes and genetic
      background. CONCLUSIONS: This paper shows the significant level of diversity
      existing in a parental population of potato as well as the putative phylogenetic
      relationships among the genotypes. The use of easily measurable phenotypic traits
      among highly contrasting genotypes could be a reasonable approach to estimate
      population structure in the initial phases of a potato breeding program.

PMID- 29338688
TI  - Transurethral resection of the prostate provides more favorable clinical outcomes
      compared with conservative medical treatment in patients with urinary retention
      caused by benign prostatic obstruction.
AB  - BACKGROUND: To evaluate the long-term surgical outcomes of patients with urinary
      retention (UR) caused by a benign prostatic obstruction (BPO) who underwent
      transurethral resection of the prostate (TURP), and compare their outcomes with
      those of patients who received medication without surgical intervention. METHODS:
      This retrospective cohort study analyzed claims data collected during the period
      of 1997-2012 from Taiwan's National Health Insurance Research Database. We
      examined geriatric adverse events among patients who had received a diagnosis of
      symptomatic benign prostatic hyperplasia and whom experienced UR, and compared
      those who received TURP and medication only. Primary outcomes included urinary
      tract infection (UTI), UR, inguinal hernia, hemorrhoids, stroke, acute myocardial
      infarction, and bony fracture. We excluded patients who had concomitant prostate
      cancer, bladder cancer, or a long-term urinary catheter indwelling, as well as
      those who did not receive alpha-blocker medication regularly. Those aged <50 or
      >90 years were also excluded. The enrolled patients were categorized into TURP (n
      = 1218) and medication only (n = 795) groups. After 1:1 propensity score
      matching, we recorded and compared patients' characteristics, postoperative
      clinical outcomes, and geriatric adverse events. RESULTS: The TURP cohort had a
      lower incidence of UTI and UR during the postoperative follow-up period from 2
      months to 3 years than did the medication only group (20.7% vs. 28.9% and 12.5%
      vs. 27.6%, respectively, p < 0.001). The life-long bone fracture incidence was
      also lower in the TURP cohort (7.9% vs. 9.2%, p = 0.048). The incidence of other
      outcomes during the postoperative follow-up period did not differ between the two
      groups. CONCLUSIONS: Compared with conservative treatment, TURP provides more
      favorable clinical outcomes in patients with UR caused by BPO. Patients who
      underwent TURP had a lower risk of UTI, repeat UR episodes, and emergent bony
      fracture. Thus, early surgical intervention should be considered for such
      patients.

PMID- 29338690
TI  - Multimorbidity patterns in the elderly: a prospective cohort study with cluster
      analysis.
AB  - BACKGROUND: Multimorbidity is the coexistence of more than two chronic diseases
      in the same individual; however, there is no consensus about the best definition.
      In addition, few studies have described the variability of multimorbidity
      patterns over time. The aim of this study was to identify multimorbidity patterns
      and their variability over a 6-year period in patients older than 65 years
      attended in primary health care. METHODS: A cohort study with yearly cross
      sectional analysis of electronic health records from 50 primary health care
      centres in Barcelona. Selected patients had multimorbidity and were 65 years of
      age or older in 2009. Diagnoses (International Classification of Primary Care,
      second edition) were extracted using O'Halloran criteria for chronic diseases.
      Multimorbidity patterns were identified using two steps: 1) multiple
      correspondence analysis and 2) k-means clustering. Analysis was stratified by sex
      and age group (65-79 and >=80 years) at the beginning of the study period.
      RESULTS: Analysis of 2009 electronic health records from 190,108 patients with
      multimorbidity (59.8% women) found a mean age of 71.8 for the 65-79 age group and
      84.16 years for those over 80 (Standard Deviation [SD] 4.35 and 3.46,
      respectively); the median number of chronic diseases was seven (Interquartil
      range [IQR] 5-10). We obtained 6 clusters of multimorbidity patterns (1
      nonspecific and 5 specifics) in each group, being the specific ones:
      Musculoskeletal, Endocrine-metabolic, Digestive/Digestive-respiratory,
      Neurological, and Cardiovascular patterns. A minimum of 42.5% of the sample
      remained in the same pattern at the end of the study, reflecting the stability of
      these patterns. CONCLUSIONS: This study identified six multimorbidity patterns
      per each group, one nonnspecific pattern and five of them with a specific pattern
      related to an organic system. The multimorbidity patterns obtained had similar
      characteristics throughout the study period. These data are useful to improve
      clinical management of each specific subgroup of patients showing a particular
      multimorbidity pattern.

PMID- 29338689
TI  - Variants of cancer susceptibility genes in Korean BRCA1/2 mutation-negative
      patients with high risk for hereditary breast cancer.
AB  - BACKGROUND: We evaluated the incidence and spectrum of pathogenic and likely
      pathogenic variants of cancer susceptibility genes in BRCA1/2 mutation-negative
      Korean patients with a high risk for hereditary breast cancer using a
      comprehensive multigene panel that included 35 cancer susceptibility genes.
      METHODS: Samples from 120 patients who were negative for BRCA1/2 mutations, but
      had been diagnosed with breast cancer that was likely hereditary, were
      prospectively evaluated for the prevalence of high-penetrance and moderate
      penetrance germline mutations. RESULTS: Nine patients (7.5%) had at least one
      pathogenic or likely pathogenic variant. Ten variants were identified in these
      patients: TP53 in two patients, PALB2 in three patients, BARD1 in two patients,
      BRIP1 in two patients, and MRE11A in one patient. We also identified 30 types of
      139 variants of unknown significance (VUS). High-penetrance germline mutations,
      including TP53 and PALB2, tended to occur with high frequency in young (< 35
      years) breast cancer patients (4/19, 21.1%) than in those diagnosed with breast
      cancer at >=35 years of age (1/101, 1.0%; p = 0.003). CONCLUSIONS: These combined
      results demonstrate that multigene panels offer an alternative strategy for
      identifying veiled pathogenic and likely pathogenic mutations in breast cancer
      susceptibility genes.

PMID- 29338691
TI  - mORCA: ubiquitous access to life science web services.
AB  - BACKGROUND: Technical advances in mobile devices such as smartphones and tablets
      have produced an extraordinary increase in their use around the world and have
      become part of our daily lives. The possibility of carrying these devices in a
      pocket, particularly mobile phones, has enabled ubiquitous access to Internet
      resources. Furthermore, in the life sciences world there has been a vast
      proliferation of data types and services that finish as Web Services. This
      suggests the need for research into mobile clients to deal with life sciences
      applications for effective usage and exploitation. RESULTS: Analysing the current
      features in existing bioinformatics applications managing Web Services, we have
      devised, implemented, and deployed an easy-to-use web-based lightweight mobile
      client. This client is able to browse, select, compose parameters, invoke, and
      monitor the execution of Web Services stored in catalogues or central
      repositories. The client is also able to deal with huge amounts of data between
      external storage mounts. In addition, we also present a validation use case,
      which illustrates the usage of the application while executing, monitoring, and
      exploring the results of a registered workflow. The software its available in the
      Apple Store and Android Market and the source code is publicly available in
      Github. CONCLUSIONS: Mobile devices are becoming increasingly important in the
      scientific world due to their strong potential impact on scientific applications.
      Bioinformatics should not fall behind this trend. We present an original software
      client that deals with the intrinsic limitations of such devices and propose
      different guidelines to provide location-independent access to computational
      resources in bioinformatics and biomedicine. Its modular design makes it easily
      expandable with the inclusion of new repositories, tools, types of visualization,
      etc.

PMID- 29338692
TI  - Emerging roles for microRNA in the regulation of Drosophila circadian clock.
AB  - BACKGROUND: The circadian clock, which operates within an approximately 24-h
      period, is closely linked to the survival and fitness of almost all living
      organisms. The circadian clock is generated through a negative transcription
      translation feedback loop. microRNAs (miRNAs) are small non-coding RNAs comprised
      of approximately 22 nucleotides that post-transcriptionally regulate target mRNA
      by either inducing mRNA degradation or inhibiting translation. RESULTS: In recent
      years, miRNAs have been found to play important roles in the regulation of the
      circadian clock, especially in Drosophila. In this review, we will use fruit
      flies as an example, and summarize the progress achieved in the study of miRNA
      mediated clock regulation. Three main aspects of the circadian clock, namely, the
      free-running period, locomotion phase, and circadian amplitude, are discussed in
      detail in the context of how miRNAs are involved in these regulations. In
      addition, approaches regarding the discovery of circadian-related miRNAs and
      their targets are also discussed. CONCLUSIONS: Research in the last decade
      suggests that miRNA-mediated post-transcriptional regulation is crucial to the
      generation and maintenance of a robust circadian clock in animals. In flies,
      miRNAs are known to modulate circadian rhythmicity and the free-running period,
      as well as circadian outputs. Further characterization of miRNAs, especially in
      the circadian input, will be a vital step toward a more comprehensive
      understanding of the functions underlying miRNA-control of the circadian clock.

PMID- 29338693
TI  - In vitro antimicrobial susceptibility testing of human Brucella melitensis
      isolates from Ulanqab of Inner Mongolia, China.
AB  - BACKGROUND: Brucellosis is an endemic disease in the Inner Mongolia Autonomous
      Region of China and Ulanqab exhibits the highest prevalence of brucellosis in
      this region. Due to the complex nature of Brucellosis, a cure for this disease
      has proven to be elusive. Furthermore, the reduced susceptibility of Brucella
      spp. to antimicrobial agents has been reported as a potential cause of
      therapeutic failure. However, detailed in vitro antimicrobial susceptibility
      patterns pertaining to Brucella isolates from this region have not yet been
      published. The aim of this study was to evaluate the antibiotic susceptibility
      profile of Brucella melitensis clinical isolates from Ulanqab, Inner Mongolia,
      China. METHODS: A total of 85 B. melitesis isolates were obtained from humans in
      Ulanqab of Inner Mongolia, China; the antimicrobial susceptibility of 85 clinical
      isolates to nine antibiotics was assessed using the E-test method according to
      the CLSI (Clinical and Laboratory Standards Institute) guidelines. RESULTS: All
      of the tested isolates were susceptible to minocycline, sparfloxacin,
      doxycycline, tetracycline, ciprofloxacin, gentamicin and levofloxacin. Resistance
      to rifampin and cotrimoxazole was observed in 1.0% (1/85) and 7.0% (6/85) of the
      isolates, respectively. However, rpoB gene mutations were not observed in single
      isolates exhibiting resistance to rifampin. CONCLUSIONS: We observed that B.
      melitensis isolates are susceptible to the majority of the tested antibiotics.
      Furthermore, minocycline and sparfloxacin exhibited extremely high bactericidal
      effects in relation to the B. melitensis isolates. The sensitivity of commonly
      used drugs for the treatment of brucellosis should be regularly monitored. To the
      best of our knowledge, this is the first report of rifampin and cotrimoxazole
      resistant isolates of B. melitensis in China. In summary, based on the findings
      from this study, we suggest that antibiotic administration and use should be
      rationalized to prevent future drug resistance.

PMID- 29338694
TI  - Development of a physical literacy model for older adults - a consensus process
      by the collaborative working group on physical literacy for older Canadians.
AB  - BACKGROUND: Arguably the uptake and usability of the physical activity (PA)
      guidelines for older adults has not been effective with only 12% of this
      population meeting the minimum guidelines to maintain health. Health promoters
      must consider innovative ways to increase PA adoption and long-term
      sustainability. Physical literacy (PL) is emerging as a promising strategy to
      increase lifelong PA participation in younger age-groups, yet there is relatively
      little evidence of PL being used to support older adults in achieving the PA
      guidelines. METHODS: An iterative and mixed-methods consensus development process
      was utilized over a series of six informed processes and meetings to develop a
      model of physical literacy for adults aged 65 years and older. RESULTS: A multi
      disciplinary collaborative working group (n = 9) from diverse practice settings
      across Canada, and representative and reflective of the full range of key
      elements of PL, was assembled. Three consensus meetings and two Delphi surveys,
      using an international cohort of 65 expert researchers, practitioners, non
      government organizations and older adults, was conducted. 45% responded on the
      first round and consensus was achieved; however, we elected to run a second
      survey to support our results. With 79% response rate, there was consensus to
      support the new PL model for older adults. CONCLUSION: Older adults are a unique
      group who have yet to be exposed to PL as a means to promote long-term PA
      participation. This new PL model uses an ecological approach to integrate PL into
      the lifestyles of most older adults. Understanding the interactions between
      components and elements that facilitate PL will ultimately provide a new and
      effective tool to target PA promotion and adherence for all older Canadians.

PMID- 29338695
TI  - Novel sensing technology in fall risk assessment in older adults: a systematic
      review.
AB  - BACKGROUND: Falls are a major health problem for older adults with significant
      physical and psychological consequences. A first step of successful fall
      prevention is to identify those at risk of falling. Recent advancement in sensing
      technology offers the possibility of objective, low-cost and easy-to-implement
      fall risk assessment. The objective of this systematic review is to assess the
      current state of sensing technology on providing objective fall risk assessment
      in older adults. METHODS: A systematic review was conducted in accordance to the
      Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement
      (PRISMA). RESULTS: Twenty-two studies out of 855 articles were systematically
      identified and included in this review. Pertinent methodological features
      (sensing technique, assessment activities, outcome variables, and fall
      discrimination/prediction models) were extracted from each article. Four major
      sensing technologies (inertial sensors, video/depth camera, pressure sensing
      platform and laser sensing) were reported to provide accurate fall risk
      diagnostic in older adults. Steady state walking, static/dynamic balance, and
      functional mobility were used as the assessment activity. A diverse range of
      diagnostic accuracy across studies (47.9% - 100%) were reported, due to variation
      in measured kinematic/kinetic parameters and modelling techniques. CONCLUSIONS: A
      wide range of sensor technologies have been utilized in fall risk assessment in
      older adults. Overall, these devices have the potential to provide an accurate,
      inexpensive, and easy-to-implement fall risk assessment. However, the variation
      in measured parameters, assessment tools, sensor sites, movement tasks, and
      modelling techniques, precludes a firm conclusion on their ability to predict
      future falls. Future work is needed to determine a clinical meaningful and easy
      to interpret fall risk diagnosis utilizing sensing technology. Additionally, the
      gap between functional evaluation and user experience to technology should be
      addressed.

PMID- 29338697
TI  - Additional dexamethasone in chemotherapies with carboplatin and paclitaxel could
      reduce the impaired glycometabolism in rat models.
AB  - BACKGROUND: Side-effects have been considered as the limitation of the
      chemotherapy agents' administration and life quality in patients with ovarian
      cancers. In order to explore the influence of the chemotherapy agents commonly
      used in ovarian cancer patients on the blood glucose metabolism in rat models, we
      conducted this study which simulated the conditions of clinical protocols.
      METHODS: Eighty clean-grade female Wistar rats were randomized into 8 groups:
      Group 1 (Negative control), Group 1' (Dexamethasone), Group 2 (Carboplatin),
      Group 2' (Carboplatin-plus-dexamethasone), Group 3 (Paclitaxel), Group 3'
      (Paclitaxel-plus-dexamethasone), Group 4 (Combined therapy), Group 4' (Combined
      therapy-plus-dexamethasone). On day 0, 4, 7 and 14, after fasted for 12 h, the
      rats in all groups underwent a glucose load and their blood glucose, glucagon and
      insulin levels were measured. RESULTS: The glucose levels in group 2, 3 and 4 at
      1 h after the loading on day 4 significantly increased (P = 0.190, 0.008 and
      0.025, respectively). The glucagon levels in group 3 and 4 showed a similar trend
      and the increase was not suppressed by the glucose loading (P < 0.001). A
      significant decrease of insulin levels in group 2, 3 and 4 were observed on day
      14 after treatment (P = 0.043, 0.019 and 0.019, respectively). The change of
      HOMA2 %B, an index reflects the ability of insulin secretion was negatively
      corresponded to the glucose levels, and the trends of HOMA2 IR, an index shows
      insulin resistance, were positively correlated to the glucose levels. The
      application of dexamethasone could reduce the degree of increased glucose levels
      significantly in group 2, 3 and 4. There were no differences in overall survival
      between the 8 groups. Edema in the stroma of pancreases was observed in group 3,
      3', 4 and 4' on day 4 after treatment (P = 0.002, 0.002, 0.000 and 0.000
      respectively) and lasted until day 14. CONCLUSIONS: Carboplatin and paclitaxel
      administration could cause a transient hyperglycemia in rats. This effect might
      occur by the combination of glucagon accumulation due to the decrease in islet
      cell secretion. The additional dexamethasone in the combination protocol of
      carboplatin and paclitaxel seemed to reduce the impaired blood glucose
      metabolism.

PMID- 29338698
TI  - Enteral immunonutrition versus enteral nutrition for gastric cancer patients
      undergoing a total gastrectomy: a systematic review and meta-analysis.
AB  - BACKGROUND: Nutrition support is a common means for patients with gastric cancer,
      especially for those undergoing elective surgery. Recently, enteral
      immunonutrition (EIN) was increasingly found to be more effective than enteral
      nutrition (EN) in enhancing the host immunity and eventually improving the
      prognosis of gastric cancer patients undergoing gastrectomy. However, the results
      reported were not consistent. This meta-analysis aimed to assess the impact of
      EIN for patients with GC on biochemical, immune indices and clinical outcomes.
      METHODS: Four electronical databases (Medline, EMBASE, Scopus and Cochrane
      library) were used to search articles in peer-reviewed, English-language
      journals. Mean difference (MD), Relative risk (RR), or standard mean difference
      (SMD) with 95% confidence interval (CI) were calculated. Heterogeneity was
      assessed by Cochrane Q and I2 statistic combined with corresponding P-value. The
      analysis was carried out with RevMan 5.3. RESULTS: Seven studies involving 583
      patients were eligible for the pooled analysis. EIN, when beyond a 7-day time
      frame post-operatively (D >= 7), increased level of CD4+ (SMD = 0.99; 95% CI,
      0.65-1.33; P < 0.00001), CD4+/ CD8+ (SMD = 0.34; 95% CI, 0.02-0.67; P = 0.04),
      the IgM (SMD = 1.15; 95% CI, 0.11-2.20; P = 0.03), the IgG (SMD = 0.98; 95% CI,
      0.55-1.42; P < 0.0001), the lymphocyte (SMD = 0.69; 95% CI, 0.32-1.06; P =
      0.0003), and the proalbumin (SMD = 0.73; 95% CI, 0.33-1.14; P = 0.0004). However,
      those increased effects were not obvious within a 7-day time-frame post
      operatively (D < 7). The levels of CD8+ and other serum proteins except
      proalbumin were not improved both on D >= 7 and D < 7. Clinical outcomes such as
      systemic inflammatory response syndrone (SIRS) (MD, - 0.89 days; 95% CI, - 1.40
      to - 0.39; P = 0.005), and postoperative complications (RR, 0.29; 95% CI, 0.14
      0.60; P = 0.001) were significantly reduced in EIN group. Pulmonary infection and
      length of hospitalization (LHS) were not improved no matter what time after
      surgery. CONCLUSIONS: EIN was found to improve the cellular immunity, modulate
      inflammatory reaction and reduce postoperative complication for GC patients
      undergoing radical gastrointestinal surgery. Exclusion of grey literature and non
      English language studies was the key limitation in this study.

PMID- 29338699
TI  - Assessing predictors of intention to prescribe sick leave among primary care
      physicians using the theory of planned behaviour.
AB  - BACKGROUND: Providing sickness certification is a decision that primary care
      physicians make on a daily basis. The majority of sickness certification studies
      in the literature involve a general assessment of physician or patient behaviour
      without the use of a robust psychological framework to guide research accuracy.
      To address this deficiency, this study utilized the Theory of Planned Behaviour
      (TPB) to specifically gauge the intention and other salient predictors related to
      sickness certification prescribing behaviour amongst primary care physicians.
      METHODS: A cross-sectional study was conducted among N = 271 primary care
      physicians from 86 primary care practices throughout two states in Malaysia.
      Questionnaires used were specifically developed based on the TPB, consisting of
      both direct and indirect measures related to the provision of sickness leave.
      Questionnaire validity was established through factor analysis and the
      determination of internal consistency between theoretically related constructs.
      The temporal stability of the indirect measures was determined via the test
      retest correlation analysis. Structural equation modelling was conducted to
      determine the strength of predictors related to intentions. RESULTS: The mean
      scores for intention to provide patients with sickness was low. The Cronbach
      alpha value for the direct measures was good: overall physician intent to provide
      sick leave (0.77), physician attitude towards prescribing sick leave for patients
      (0.77) and physician attitude in trusting the intention of patients seeking sick
      leave (0.83). The temporal stability of the indirect measures of the
      questionnaire was satisfactory with significant correlation between constructs
      separated by an interval of two weeks (p < 0.05). Attitudes and subjective norms
      were identified as important predictors in physician intention to provide sick
      leave to patients. CONCLUSION: An integrated behavioural model utilizing the TPB
      could help fully explain the complex act of providing sickness leave to patients.
      Findings from this study could assist relevant agencies to facilitate the
      creation of policies that may help regulate the provision of sickness leave and
      alleviate the work burden of sickness leave tasks faced by physicians in
      Malaysia.

PMID- 29338696
TI  - Transcriptional responses of Escherichia coli during recovery from inorganic or
      organic mercury exposure.
AB  - BACKGROUND: The protean chemical properties of mercury have long made it
      attractive for diverse applications, but its toxicity requires great care in its
      use, disposal, and recycling. Mercury occurs in multiple chemical forms, and the
      molecular basis for the distinct toxicity of its various forms is only partly
      understood. Global transcriptomics applied over time can reveal how a cell
      recognizes a toxicant and what cellular subsystems it marshals to repair and
      recover from the damage. The longitudinal effects on the transcriptome of
      exponential phase E. coli were compared during sub-acute exposure to mercuric
      chloride (HgCl2) or to phenylmercuric acetate (PMA) using RNA-Seq. RESULTS:
      Differential gene expression revealed common and distinct responses to the
      mercurials throughout recovery. Cultures exhibited growth stasis immediately
      after each mercurial exposure but returned to normal growth more quickly after
      PMA exposure than after HgCl2 exposure. Correspondingly, PMA rapidly elicited up
      regulation of a large number of genes which continued for 30 min, whereas fewer
      genes were up-regulated early after HgCl2 exposure only some of which overlapped
      with PMA up-regulated genes. By 60 min gene expression in PMA-exposed cells was
      almost indistinguishable from unexposed cells, but HgCl2 exposed cells still had
      many differentially expressed genes. Relative expression of energy production and
      most metabolite uptake pathways declined with both compounds, but nearly all
      stress response systems were up-regulated by one or the other mercurial during
      recovery. CONCLUSIONS: Sub-acute exposure influenced expression of ~45% of all
      genes with many distinct responses for each compound, reflecting differential
      biochemical damage by each mercurial and the corresponding resources available
      for repair. This study is the first global, high-resolution view of the
      transcriptional responses to any common toxicant in a prokaryotic model system
      from exposure to recovery of active growth. The responses provoked by these two
      mercurials in this model bacterium also provide insights about how higher
      organisms may respond to these ubiquitous metal toxicants.

PMID- 29338700
TI  - Correction to: A systematic comparison of copy number alterations in four types
      of female cancer.
AB  - After publication of the original article [1] the authors found that the article
      contained an incorrect version of Fig. 4. This does not affect the results and
      conclusions of the article.

PMID- 29338701
TI  - SSH1 expression is associated with gastric cancer progression and predicts a poor
      prognosis.
AB  - BACKGROUND: Slingshot homolog-1 (SSH1) plays an important role in pathological
      processes, including in the occurrence and development of tumours. The purpose of
      this study was to determine whether SSH1 is a key biomarker with prognostic value
      for survival in patients with gastric cancer. METHODS: We performed
      immunohistochemistry (IHC) on tissue microarrays containing 100 gastric cancer
      specimens to evaluate SSH1 protein expression. The association of pathological
      characteristics with cumulative survival was determined by Kaplan-Meier analysis.
      A Cox proportional hazards model was generated in the multi-factorial survival
      analysis to identify univariate prognostic factors of GC. RESULTS: SSH1
      expression level in gastric cancer tissues was significantly associated with
      lymph node metastasis (P = 0.032). Additionally, multivariate regression analysis
      clearly indicated that SSH1 expression was significantly correlated with poor
      clinical outcomes of patients with gastric cancer (P = 0.016). Multivariate
      analyses showed that SSH1 was the best predictor of poor prognosis in patients
      with gastric cancer (P = 0.030). CONCLUSIONS: SSH1 expression is associated with
      gastric cancer progression and predicts a poor prognosis. SSH1 may play an
      important role in the development of gastric cancer, and it is a promising target
      for prevention and/or treatment of gastric cancer.

PMID- 29338702
TI  - Estimating the scale of chronic hepatitis C virus infection in the EU/EEA: a
      focus on migrants from anti-HCV endemic countries.
AB  - BACKGROUND: Increasing the proportion diagnosed with and on treatment for chronic
      hepatitis C (CHC) is key to the elimination of hepatitis C in Europe. This study
      contributes to secondary prevention planning in the European Union/European
      Economic Area (EU/EEA) by estimating the number of CHC (anti-HCV positive and
      viraemic) cases among migrants living in the EU/EEA and born in endemic
      countries, defining the most affected migrant populations, and assessing whether
      country of birth prevalence is a reliable proxy for migrant prevalence. METHODS:
      Migrant country of birth and population size extracted from statistical databases
      and anti-HCV prevalence in countries of birth and in EU/EEA countries derived
      from a systematic literature search were used to estimate caseload among and most
      affected migrants. Reliability of country of birth prevalence as a proxy for
      migrant prevalence was assessed via a systematic literature search. RESULTS:
      Approximately 11% of the EU/EEA adult population is foreign-born, 79% of whom
      were born in endemic (anti-HCV prevalence >=1%) countries. Anti-HCV/CHC
      prevalence in migrants from endemic countries residing in the EU/EEA is estimated
      at 2.3%/1.6%, corresponding to ~580,000 CHC infections or 14% of the CHC disease
      burden in the EU/EEA. The highest number of cases is found among migrants from
      Romania and Russia (50-60,000 cases each) and migrants from Italy, Morocco,
      Pakistan, Poland and Ukraine (25-35,000 cases each). Ten studies reporting
      prevalence in migrants in Europe were identified; in seven of these estimates,
      prevalence was comparable with the country of birth prevalence and in three
      estimates it was lower. DISCUSSION: Migrants are disproportionately affected by
      CHC, account for a considerable number of CHC infections in EU/EEA countries, and
      are an important population for targeted case finding and treatment. Limited data
      suggest that country of birth prevalence can be used as a proxy for the
      prevalence in migrants.

PMID- 29338703
TI  - Diagnostic accuracy and prediction increment of markers of epithelial-mesenchymal
      transition to assess cancer cell detachment from primary tumors.
AB  - BACKGROUND: Metastases play a role in about 90% of cancer deaths. Markers of
      epithelial-mesenchymal transition (EMT) measured in primary tumor cancer cells
      might provide diagnostic information about the likelihood that cancer cells have
      detached from the primary tumor. Used together with established diagnostic tests
      of detachment-lymph node evaluation and radiologic imaging-EMT marker
      measurements might improve the ability of clinicians to assess the patient's risk
      of metastatic disease. Translation of EMT markers to clinical use has been
      hampered by a lack of valid analyses of clinically-informative parameters. Here,
      we demonstrate a rigorous approach to estimating the sensitivity, specificity,
      and prediction increment of an EMT marker to assess cancer cell detachment from
      primary tumors. METHODS: We illustrate the approach using immunohistochemical
      measurements of the EMT marker E-cadherin in a set of colorectal primary tumors
      from a population-based prospective cohort in North Carolina. Bayesian latent
      class analysis was used to estimate sensitivity and specificity in a setting of
      multiple imperfect diagnostic tests and no gold standard. Risk reclassification
      analysis was used to assess the extent to which addition of the marker to the
      panel of established diagnostic tests would improve mortality prediction. We
      explored how changing the latent class conditional dependence assumptions and
      definition of marker positivity would impact the results. RESULTS: All diagnostic
      accuracy and prediction increment statistics varied with the choice of cut point
      to define marker positivity. When comparing different definitions of marker
      positivity to each other, numerous trade-offs were observed in terms of
      sensitivity, specificity, predictive discrimination, and prediction model
      calibration. We then discussed several implementation considerations and the
      plausibility of analytic assumptions. CONCLUSIONS: The approaches presented here
      can be extended to any EMT marker, to most forms of cancer, and to different
      kinds of EMT marker measurements, such as RNA or gene methylation data. These
      methods provide valid, clinically-informative assessment of whether and how to
      use a given EMT marker to refine tumor staging and consequent treatment
      decisions.

PMID- 29338704
TI  - Alcohol marketing on YouTube: exploratory analysis of content adaptation to
      enhance user engagement in different national contexts.
AB  - BACKGROUND: We know little about how social media alcohol marketing is utilized
      for alcohol promotion in different national contexts. There does not appear to be
      any academic work on online exposure to alcohol marketing via social media in
      India, and most of the limited research in Australia has focused on Facebook.
      Hence, the present study extends previous research by investigating alcohol
      promotion conducted on an under-researched form of social media (YouTube) in two
      contrasting geographic contexts. This study examines and compares the types of
      strategies used by marketers on Indian and Australian alcohol brands with the
      greatest YouTube presence, and the extent to which users engage with these
      strategies. METHODS: The 10 alcohol brands per country with the greatest YouTube
      presence were identified based on the number of 'subscriptions'. The number of
      videos, views per video, and the type of content within the videos were collected
      for each brand. The data were analyzed using an inductive coding approach, using
      NVivo 10. RESULTS: The targeted brands had gathered 98,881 subscriptions (Indian
      brands: n = 13,868; Australian brands: n = 85,013). The type of marketing
      strategies utilized by brands were a mix of those that differed by country (e.g.
      sexually suggestive content in India and posts related to the brand's tradition
      or heritage in Australia) and generic approaches (e.g. encouraging time- and
      event-specific drinking; demonstrations of food/cocktail recipes; camaraderie;
      competitions and prize draws; and brand sponsorship at music, sports, and fashion
      events). CONCLUSIONS: This cross-national comparison demonstrates that YouTube
      provides alcohol marketers with an advertising platform where they utilize
      tailored marketing approaches to cater to specific national contexts and develop
      content on the cultural meanings users invoke in their interactions with these
      strategies. Those exposed to alcohol marketing on YouTube are likely to include
      those under the legal drinking age.

PMID- 29338705
TI  - Frailty as a predictor of hospital length of stay after elective total joint
      replacements in elderly patients.
AB  - BACKGROUND: Total joint replacement procedures are increasing in number because
      of population aging and osteoarthritis development. Defined as a lack of
      physiological reserves and the inability to adequately respond to external
      stressors, frailty may be more common than expected in older patients with
      degenerative arthritis awaiting total joint replacements. The aim of the present
      study was to assess associations between frailty and adverse outcomes, frailty
      prevalence among elderly patients awaiting elective TJR, and agreement between 2
      frailty screening instruments. METHODS: We undertook a prospective,
      observational, pilot study in our institution. We enrolled patients 65 years or
      older who were awaiting elective knee or hip replacement surgery and evaluated
      them in our preoperative clinic with planned postoperative hospital length of
      stay greater than 24 h. Patients were asked to grade their perceived well-being
      on the Clinical Frailty Scale and to answer questions on the FRAIL Scale.
      RESULTS: The Clinical Frailty Scale classified 40 patients (45.9%) as robust, 43
      patients (49.4%) as prefrail and 4 patients (4.5%) as frail, while the FRAIL
      Scale categorized 12 patients (13.7%) as robust, 54 patients (62.0%) as prefrail,
      and 20 patients (22.9%) as frail. Robustness, ascertained on the Clinical Frailty
      Scale was, while the FRAIL Scale was not, significantly associated with shorter
      hospital length of stay and fewer discharges to the rehabilitation center. Both
      scales showed moderate mutual agreement. CONCLUSION: Screening for frailty
      identified between 5% and 10% of patients at risk of adverse outcomes. The
      Clinical Frailty Scale was, while the FRAIL scale was not, significantly
      associated with hospital length of stay and discharge to rehabilitation center in
      our cohort of total joint replacement patients.

PMID- 29338706
TI  - Miliary tuberculosis with co-existing pulmonary cryptococcosis in non-HIV patient
      without underlying diseases: a case report.
AB  - BACKGROUND: Tuberculosis and cryptococcosis co-infection usually occurs in
      immunosuppressed patients with impaired cell-mediated immunity. However, there
      are few reports about such co-infection in non-HIV patients without underlying
      diseases. Here, we report a case of miliary tuberculosis with co-existing
      pulmonary cryptococcosis in non-HIV patient without underlying diseases. CASE
      PRESENTATION: An 84-year-old Asian female presented to our hospital with
      complaints of a 1-week history of abdominal pain and appetite loss. Chest
      computed tomography (CT) showed diffuse micronodules in random patterns in both
      lung fields. Liver, skin and bone marrow biopsies showed epithelioid cell
      granuloma. Polymerase chain reaction of gastric aspirate was positive for
      Mycobacterium tuberculosis. According to these findings, miliary tuberculosis was
      suspected and antimycobacterial therapy was initiated. After a 6-month treatment
      course, chest radiograph showed new multiple nodules in the right middle lung
      field. Chest CT showed that a right S6 small nodule was increased and new
      multiple nodules appeared in the right lower lobe. Flexible fiberoptic
      bronchoscopy was subsequently perfomed. Cytology of the bronchial lavage showed a
      small number of Periodic acid-Schiff-positive bodies, suggesting Cryptococcus
      species. Moreover, serum cryptococcal antigen testing was positive. According to
      these findings, pulmonary cryptococcosis was diagnosed, although the culture was
      negative. Oral fluconazole therapy was subsequently initiated. After a 6-month
      treatment course, chest radiograph showed gradual improvement. CONCLUSION:
      Although tuberculosis and cryptococcosis co-infection is relatively rare in
      immunocompromised hosts, such as those with acquired immunodeficiency syndrome,
      clinicians should be aware that these infections can co-exist even in non-HIV
      patients without underlying diseases.

PMID- 29338707
TI  - Is the likelihood of spousal violence lower or higher among childless women?
      Evidence from Nigeria demographic and health surveys.
AB  - BACKGROUND: Few studies have been able to determine whether the likelihood of
      spousal violence is higher or lower among childless women compared with women who
      have children. This is because most studies linking childlessness and spousal
      violence were either qualitative or were conducted among childless women
      attending fertility clinics. In the fewer quantitative studies that linked
      childlessness and spousal violence, results are mixed and yet to be verified in
      Nigeria using nationally representative sample data. The current study addresses
      this knowledge gap by raising the research question: is the likelihood of spousal
      violence lower or higher among childless women? METHODS: The study analysed data
      from 2008 and 2013 Nigeria Demographic and Health Surveys. Only women aged 35-49
      years are included in the analysis. The outcome variable was spousal violence,
      while the key explanatory variable was parity status categorised into childless,
      have only one child, and have two or more children. Selected individual-level and
      community-level variables were included as additional explanatory variables. The
      multilevel mixed-effects logistic regression analysis was applied in four nested
      models using Stata 12. RESULTS: In Model 1, result show 57% more likelihood of
      spousal violence among women who have two or more children compared with
      childless women (OR = 1.570: CI: 1.074-2.294). In Model 2, women who have two or
      more children were 52.3% more likely to experience spousal violence compared with
      childless women (OR = 1.523; CI: 1.037-2.247). In Model 3, the likelihood of
      spousal violence was 67.2% higher among women who have two or more children
      compared with childless women (OR = 1.672; CI: 1.140-2.452). In the full model,
      women who have two or more children were 50.8% more likely to experience spousal
      violence compared with childless women (OR = 1.508; CI: 1.077-2.234). The Intra
      Class Correlation (ICC) provides evidence to support community contributions to
      prevalence of spousal violence. CONCLUSIONS: The likelihood of spousal violence
      is lower among childless women in Nigeria. Causes of spousal violence against
      women cut across individual, family, and community characteristics irrespective
      of childlessness or number of children. Current Behaviour Change Communication
      should be strengthened by adequate enforcement of the newly enacted Violence
      Against Persons (Prohibition) Act of 2015.

PMID- 29338708
TI  - Patterns of illness disclosure among Indian slum dwellers: a qualitative study.
AB  - BACKGROUND: Slum dwellers display specific traits when it comes to disclosing
      their illnesses to professionals. The resulting actions lead to poor health
      seeking behaviour and underutilisation of existing formal health facilities. The
      ways that slum people use to communicate their feelings about illness, the type
      of confidants that they choose, and the supportive and unsupportive social and
      cultural interactions to which they are exposed have not yet been studied in the
      Indian context, which constitutes an important knowledge gap for Indian
      policymakers and practitioners alike. To that end, this study examines the
      patterns of illness disclosure in Indian slums and the underpinning factors which
      shape the slum dwellers' disclosing attitude. METHODS: In-depth, semi-structured
      interviews were conducted among 105 men and 113 women who experienced illness in
      the year prior to the study period. Respondents were selected from four urban
      slums in two Indian cities, Bangalore and Kolkata. RESULTS: Findings indicate
      that women have more confidants at different social levels, while men have a
      limited network of disclosures which is culturally and socially mediated. Gender
      role limitations, exclusion from peer groups and unsupportive local situations
      are the major cause of disclosure delay or non-disclosure among men, while the
      main concerns for women are a lack of proper knowledge about illness,
      unsupportive responses received from other people on certain occasions, the fear
      of social stigma, material loss and the burden of the local situation. Prompt
      sharing of illness among men is linked with prevention intention and coping with
      biological problems, whereas factors determining disclosure for women relate to
      ensuring emotional and instrumental safety, preventing collateral damage of
      illness, and preventing and managing biological complications. CONCLUSIONS: The
      findings reveal that patterns of disclosure are not determined by the
      acknowledgment of illness but largely depend on the interplay between individual
      agency, disclosure consequences and the socio cultural environment. The results
      of this study can contribute significantly to mitigating the pivotal knowledge
      gap between health policymakers, practitioners and patients, leading to the
      formulation of policies that maximise the utilisation of health facilities in
      slums.

PMID- 29338709
TI  - WorMachine: machine learning-based phenotypic analysis tool for worms.
AB  - BACKGROUND: Caenorhabditis elegans nematodes are powerful model organisms, yet
      quantification of visible phenotypes is still often labor-intensive, biased, and
      error-prone. We developed WorMachine, a three-step MATLAB-based image analysis
      software that allows (1) automated identification of C. elegans worms, (2)
      extraction of morphological features and quantification of fluorescent signals,
      and (3) machine learning techniques for high-level analysis. RESULTS: We examined
      the power of WorMachine using five separate representative assays: supervised
      classification of binary-sex phenotype, scoring continuous-sexual phenotypes,
      quantifying the effects of two different RNA interference treatments, and
      measuring intracellular protein aggregation. CONCLUSIONS: WorMachine is suitable
      for analysis of a variety of biological questions and provides an accurate and
      reproducible analysis tool for measuring diverse phenotypes. It serves as a
      "quick and easy," convenient, high-throughput, and automated solution for
      nematode research.

PMID- 29338710
TI  - A genetically encoded Ca2+ indicator based on circularly permutated sea anemone
      red fluorescent protein eqFP578.
AB  - BACKGROUND: Genetically encoded calcium ion (Ca2+) indicators (GECIs) are
      indispensable tools for measuring Ca2+ dynamics and neuronal activities in vitro
      and in vivo. Red fluorescent protein (RFP)-based GECIs have inherent advantages
      relative to green fluorescent protein-based GECIs due to the longer wavelength
      light used for excitation. Longer wavelength light is associated with decreased
      phototoxicity and deeper penetration through tissue. Red GECI can also enable
      multicolor visualization with blue- or cyan-excitable fluorophores. RESULTS: Here
      we report the development, structure, and validation of a new RFP-based GECI, K
      GECO1, based on a circularly permutated RFP derived from the sea anemone
      Entacmaea quadricolor. We have characterized the performance of K-GECO1 in
      cultured HeLa cells, dissociated neurons, stem-cell-derived cardiomyocytes,
      organotypic brain slices, zebrafish spinal cord in vivo, and mouse brain in vivo.
      CONCLUSION: K-GECO1 is the archetype of a new lineage of GECIs based on the RFP
      eqFP578 scaffold. It offers high sensitivity and fast kinetics, similar or better
      than those of current state-of-the-art indicators, with diminished lysosomal
      accumulation and minimal blue-light photoactivation. Further refinements of the K
      GECO1 lineage could lead to further improved variants with overall performance
      that exceeds that of the most highly optimized red GECIs.

PMID- 29338711
TI  - Blood parasite infections in a wild population of ravens (Corvus corax) in
      Bulgaria.
AB  - BACKGROUND: Blood parasites have been studied intensely in many families of avian
      hosts, but corvids, a particularly cosmopolitan family, remain underexplored.
      Haemosporidian parasites of the common raven (Corvus corax) have not been
      studied, although it is the largest, most adaptable, and widespread corvid.
      Genetic sequence data from parasites of ravens can enhance the understanding of
      speciation patterns and specificity of haemosporidian parasites in corvids, and
      shed light how these hosts cope with parasite pressure. METHODS: A baited cage
      trap was used to catch 86 ravens and a nested PCR protocol was used to amplify a
      479 bp fragment of the haemosporidian cytochrome b gene from the samples. The
      obtained sequences were compared with the MalAvi database of all published
      haemosporidian lineages and a phylogenetic tree including all detected raven
      parasites was constructed. An examination of blood smears was performed for
      assessment of infection intensity. RESULTS: Twenty blood parasite lineages were
      recovered from ravens caught in a wild population in Bulgaria. The prevalence of
      generalist Plasmodium lineages was 49%, and the prevalence of Leucocytozoon
      lineages was 31%. Out of 13 detected Leucocytozoon lineages six were known from
      different corvids, while seven others seem to be specific to ravens. A
      phylogenetic reconstruction suggests that Leucocytozoon lineages of ravens and
      other corvids are not monophyletic, with some groups appearing closely related to
      parasites of other host families. CONCLUSIONS: Several different, morphologically
      cryptic groups of Leucocytozoon parasites appear to infect corvids. Ravens
      harbour both generalist corvid Leucocytozoon as well as apparently species
      specific lineages. The extraordinary breeding ecology and scavenging lifestyle
      possibly allow ravens to evade vectors and have relatively low blood parasite
      prevalence compared to other corvids.

PMID- 29338712
TI  - Association between the level of education and knowledge, attitudes and practices
      regarding dengue in the Caribbean region of Colombia.
AB  - BACKGROUND: Community integration in dengue control requires assessments of
      knowledge, attitudes and practices (KAPs), which can vary widely according to
      demographic and educational factors. We aimed to describe and compare the KAPs
      according to level of education in municipalities in the Caribbean region of
      Colombia. METHODS: A survey was administered from October to December 2015,
      including families selected through probabilistic sampling in eleven
      municipalities. The analysis focused on the comparative description of the
      responses according to level of education. The KAP prevalence ratios (PR)
      according to education were estimated using Poisson regression (robust),
      including age and sex as adjustment variables. RESULTS: Out of 1057 participants,
      1054 (99.7%) surveys were available for analysis, including 614 (58.3%) who had a
      high school level of education or higher and 440 (41.7%) who had a lower level of
      education (not high school graduates). The high school graduates showed a higher
      frequency of correct answers in relation to knowledge about dengue symptoms and
      transmission. On the other hand, graduates showed a higher probability of
      practices and attitudes that favor dengue control, including not storing water in
      containers (PR: 2.2; 95% Confidence Interval [CI]: 1.42-3.43), attend community
      meetings (PR: 1.33; 95% CI: 1.07-1.65), educate family members and neighbors in
      prevention measures (PR: 1.35; 95% CI: 1.15-1.59). CONCLUSIONS: Level of
      education could be a key determinant of knowledge of the disease and its
      transmission, as well as attitudes and practices, especially those that involve
      the integration of community efforts for dengue control.

PMID- 29338713
TI  - LncRNA DANCR involved osteolysis after total hip arthroplasty by regulating FOXO1
      expression to inhibit osteoblast differentiation.
AB  - BACKGROUND: Aseptic loosening of artificial hip joint is a major complication
      affecting the long-term use of the artificial hip joint, and is the main cause of
      joint replacement failure. However, the mechanism of aseptic loosening of THR has
      not yet cleared. The aim of this study was to investigate the underlying
      mechanism of DANCR in osteoblast differentiation (OD). METHODS: We detected the
      expressions of DANCR and FOXO1 in clinical samples and mesenchymal stem cells
      (MSCs) by qRT-PCR and western blotting. The effects of polymethylmethacrylate
      (PMMA) on OD of MSCs were examined by alkaline phosphatase (ALP) activity and
      Alizarin Red S (ARS) staining. The expressions of OD markers were measured by qRT
      PCR and western blotting. The mechanism of DANCR in OD was detected by RNA pull
      down, RNA immunoprecipitation (RIP) assay and ubiquitination assays. RESULTS:
      Compared with the surrounding normal tissues, DANCR expression was up-regulated
      and FOXO1 expression was down-regulated in periprosthetic tissues. PMMA
      suppressed ALP activity, increased DANCR expression, and decreased the
      expressions of FOXO1, Runx2, Osterix (Ostx) and osteocalcin (OCN). ARS staining
      showed that PMMA inhibited the OD of MSCs. Knockdown of DANCR attenuated the
      inhibitory effect of PMMA on OD. Knockdown of FOXO1 could reverse the effect of
      si-DANC. RNA pull-down and RIP assay implicated that DANCR bound to FOXO1.
      Ubiquitination assay indicated that si-DANCR could repress Skp2-mediated
      ubiquitination of FOXO1. CONCLUSION: LncRNA DANCR could inhibit OD by regulating
      FOXO1 expression.

PMID- 29338714
TI  - The effects of metformin in type 1 diabetes mellitus.
AB  - BACKGROUND: This retrospective study investigated the effect of adding metformin
      to pharmacologic insulin dosing in type 1 diabetics on insulin therapy 1 year
      after treatment compared with patients on insulin therapy alone. METHODS: Twenty
      nine adults with type 1 diabetes who had metformin added to their insulin therapy
      for 12 months were compared with 29 adults with type 1 diabetes who remained on
      insulin-alone therapy. RESULTS: Fifty-eight patients with C peptide negative-type
      1 diabetics (26 females, mean age: 29.01 +/- 7.03 years, BMI: 24.18 +/- 3.16
      kg/m2) were analyzed. Age, sex, body weight, insulin dose requirement, plasma
      glucose (PG), blood pressure (BP), and lipids did not differ between groups
      before treatment (p > 0.05). Metabolic syndrome (44.8 vs 41.4%, p > 0.05) did not
      differ between the metformin-insulin and insulin alone groups before treatment.
      Metabolic syndrome was more decreased in the metformin-insulin group than in the
      insulin alone group after treatment (-8.9 +/- 1.3 vs. 2.5 +/- 0.6%, p = 0.028).
      Insulin dose requirement was lower in the metformin-insulin group than in the
      insulin alone group (-0.03 vs. 0.11 IU/kg/d, p = 0.006). Fasting PG (-26.9 +/-
      54.2 vs. 0.7 +/- 29.5 mg/dL, p = 0.022) and postprandial PG (-43.1 +/- 61.8 mg/dL
      vs. -3.1 +/- 40.1 mg/dL, p = 0.010) was more decreased in the metformin-insulin
      group than in the insulin alone group. Body weight, lipids, and HbA1c did not
      differ between the groups (p > 0.05). CONCLUSIONS: Metformin decreased glucose
      concentrations, reduced metabolic syndrome, as well as insulin dose requirement
      more than insulin therapy alone, 1 year after treatment. These results were
      independent of blood lipid improvement or weight loss, although on average weight
      remained decreased with metformin-insulin therapy, whereas the average weight
      increased with insulin therapy alone.

PMID- 29338715
TI  - Landscape genomics: natural selection drives the evolution of mitogenome in
      penguins.
AB  - BACKGROUND: Mitochondria play a key role in the balance of energy and heat
      production, and therefore the mitochondrial genome is under natural selection by
      environmental temperature and food availability, since starvation can generate
      more efficient coupling of energy production. However, selection over
      mitochondrial DNA (mtDNA) genes has usually been evaluated at the population
      level. We sequenced by NGS 12 mitogenomes and with four published genomes,
      assessed genetic variation in ten penguin species distributed from the equator to
      Antarctica. Signatures of selection of 13 mitochondrial protein-coding genes were
      evaluated by comparing among species within and among genera (Spheniscus,
      Pygoscelis, Eudyptula, Eudyptes and Aptenodytes). The genetic data were
      correlated with environmental data obtained through remote sensing (sea surface
      temperature [SST], chlorophyll levels [Chl] and a combination of SST and Chl
      [COM]) through the distribution of these species. RESULTS: We identified the
      complete mtDNA genomes of several penguin species, including ND6 and 8 tRNAs on
      the light strand and 12 protein coding genes, 14 tRNAs and two rRNAs positioned
      on the heavy strand. The highest diversity was found in NADH dehydrogenase genes
      and the lowest in COX genes. The lowest evolutionary divergence among species was
      between Humboldt (Spheniscus humboldti) and Galapagos (S. mendiculus) penguins
      (0.004), while the highest was observed between little penguin (Eudyptula minor)
      and Adelie penguin (Pygoscelis adeliae) (0.097). We identified a signature of
      purifying selection (Ka/Ks < 1) across the mitochondrial genome, which is
      consistent with the hypothesis that purifying selection is constraining
      mitogenome evolution to maintain Oxidative phosphorylation (OXPHOS) proteins and
      functionality. Pairwise species maximum-likelihood analyses of selection at codon
      sites suggest positive selection has occurred on ATP8 (Fixed-Effects Likelihood,
      FEL) and ND4 (Single Likelihood Ancestral Counting, SLAC) in all penguins. In
      contrast, COX1 had a signature of strong negative selection. ND4 Ka/Ks ratios
      were highly correlated with SST (Mantel, p-value: 0.0001; GLM, p-value: 0.00001)
      and thus may be related to climate adaptation throughout penguin speciation.
      CONCLUSIONS: These results identify mtDNA candidate genes under selection which
      could be involved in broad-scale adaptations of penguins to their environment.
      Such knowledge may be particularly useful for developing predictive models of how
      these species may respond to severe climatic changes in the future.

PMID- 29338716
TI  - Donor age affects proteome composition of tenocyte-derived engineered tendon.
AB  - BACKGROUND: The concept of tissue engineering is to deliver to the injury site
      biological scaffolds carrying functional cells that will enhance healing
      response. The preferred cell source is autologous in order to reduce immune
      response in the treated individual. However, in elderly patients age-related
      changes in synthetic activity of the implanted cells and subsequent alterations
      in tissue protein content may affect therapeutic outcomes. In this study we
      investigated the effect of donor age on proteome composition of tenocyte-derived
      tendon tissue-engineered constructs. RESULTS: Liquid chromatography tandem mass
      spectrometry was used to assess the proteome of tissue-engineered constructs
      derived from young and old equine tenocytes. Ageing was associated with altered
      extracellular matrix composition, especially accumulation of collagens (type I,
      III and XIV), and lower cytoskeletal turnover. Proteins involved in cell
      responsiveness to mechanical stimuli and cell-extracellular matrix interaction
      (calponin 1, palladin, caldesmon 1, cortactin) were affected. CONCLUSIONS: This
      study demonstrated significant changes in proteome of engineered tendon derived
      from young and old tenocytes, indicating the impact of donor age on composition
      of autologous constructs.

PMID- 29338717
TI  - Risk factors for acute respiratory infections in children under five years
      attending the Bamenda Regional Hospital in Cameroon.
AB  - BACKGROUND: Acute respiratory infections (ARI) are a leading cause of morbidity
      and mortality in under-five children worldwide. About 6.6 million children less
      than 5 years of age die every year in the world; 95% of them in low-income
      countries and one third of the total deaths is due to ARI. This study aimed at
      determining the proportion of acute respiratory infections and the associated
      risk factors in children under 5 years visiting the Bamenda Regional Hospital in
      Cameroon. METHODS: A cross-sectional analytic study involving 512 children under
      5 years was carried out from December 2014 to February 2015. Participants were
      enrolled by a consecutive convenient sampling method. A structured questionnaire
      was used to collect clinical, socio-demographic and environmental data. Diagnosis
      of ARI was based on the revised WHO guidelines for diagnosing and management of
      childhood pneumonia. The data was analyzed using the statistical software
      EpiInfoTM version 7. RESULTS: The proportion of ARIs was 54.7% (280/512), while
      that of pneumonia was 22.3% (112/512). Risk factors associated with ARI were: HIV
      infection ORadj 2.76[1.05-7.25], poor maternal education (None or primary only)
      ORadj 2.80 [1.85-4.35], exposure to wood smoke ORadj 1.85 [1.22-2.78], passive
      smoking ORadj 3.58 [1.45-8.84] and contact with someone who has cough ORadj 3.37
      [2.21-5.14]. Age, gender, immunization status, breastfeeding, nutritional status,
      fathers' education, parents' age, school attendance and overcrowding were not
      significantly associated with ARI. CONCLUSION: The proportion of ARI is high and
      is associated with HIV infection, poor maternal education, exposure to wood
      smoke, passive cigarette smoking, and contact with persons having a cough.
      Control programs should focus on diagnosis, treatment and prevention of ARIs.

PMID- 29338718
TI  - A live cell assay of GPCR coupling allows identification of optogenetic tools for
      controlling Go and Gi signaling.
AB  - BACKGROUND: Animal opsins are light-sensitive G-protein-coupled receptors (GPCRs)
      that enable optogenetic control over the major heterotrimeric G-protein signaling
      pathways in animal cells. As such, opsins have potential applications in both
      biomedical research and therapy. Selecting the opsin with the best balance of
      activity and selectivity for a given application requires knowing their ability
      to couple to a full range of relevant Galpha subunits. We present the GsX assay,
      a set of tools based on chimeric Gs subunits that transduce coupling of opsins to
      diverse G proteins into increases in cAMP levels,  measured with a real-time
      reporter in living cells. We use this assay to compare coupling to Gi/o/t across
      a panel of natural and chimeric opsins selected for potential application in gene
      therapy for retinal degeneration. RESULTS: Of the opsins tested, wild-type human
      rod opsin had the highest activity for chimeric Gs proxies for Gi and Gt (Gsi and
      Gst) and was matched in Go proxy (Gso) activity only by a human rod opsin/scallop
      opsin chimera. Rod opsin drove roughly equivalent responses via Gsi, Gso, and
      Gst, while cone opsins showed much lower activities with Gso than Gsi or Gst, and
      a human rod opsin/amphioxus opsin chimera demonstrated higher activity with Gso
      than with Gsi or Gst. We failed to detect activity for opsin chimeras bearing
      three intracellular fragments of mGluR6, and observed unexpectedly complex
      response profiles for scallop and amphioxus opsins thought to be specialized for
      Go. CONCLUSIONS: These results identify rod opsin as the most potent non
      selective Gi/o/t-coupled opsin, long-wave sensitive cone opsin as the best for
      selectively activating Gi/t over Go, and a rod opsin/amphioxus opsin chimera as
      the best choice for selectively activating Go over Gi/t.

PMID- 29338719
TI  - Preventing malaria in the Peruvian Amazon: a qualitative study in Iquitos, Peru.
AB  - BACKGROUND: In Peru, despite decades of concerted control efforts, malaria
      remains a significant public health burden. Peru has recently exhibited a
      dramatic rise in malaria incidence, impeding South America's progress towards
      malaria elimination. The Amazon basin, in particular the Loreto region of Peru,
      has been identified as a target for the implementation of intensified control
      strategies, aiming for elimination. No research has addressed why vector control
      strategies in Loreto have had limited impact in the past, despite vector control
      elsewhere being highly effective in reducing malaria transmission. This study
      employed qualitative methods to explore factors limiting the success of vector
      control strategies in the region. METHODS: Twenty semi-structured interviews were
      conducted among adults attending a primary care centre in Iquitos, Peru, together
      with 3 interviews with key informants (health care professionals). The interviews
      focussed on how local knowledge, together with social and cultural attitudes,
      determined the use of vector control methods. RESULTS: Five themes emerged. (a)
      Participants believed malaria to be embedded within their culture, and commonly
      blamed this for a lack of regard for prevention. (b) They perceived a shift in
      mosquito biting times to early evening, rendering night-time use of bed nets less
      effective. (c) Poor preventive practices were compounded by a consensus that
      malaria prevention was the government's responsibility, and that this reduced
      motivation for personal prevention. (d) Participants confused the purpose of
      space-spraying. (e) Participants' responses also exposed persisting
      misconceptions, mainly concerning the cause of malaria and best practices for its
      prevention. CONCLUSION: To eliminate malaria from the Americas, region-specific
      strategies need to be developed that take into account the local social and
      cultural contexts. In Loreto, further research is needed to explore the potential
      shift in biting behaviour of Anopheles darlingi, and how this interacts with the
      population's social behaviours and current use of preventive measures. Attitudes
      concerning personal responsibility for malaria prevention and long-standing
      misconceptions as to the cause of malaria and best preventive practices also need
      to be addressed.

PMID- 29338720
TI  - Manual exchange transfusion for severe imported falciparum malaria: a
      retrospective study.
AB  - BACKGROUND: This study was designed to evaluate the efficacy of exchange
      transfusion in patients with severe imported falciparum malaria. Twelve patients
      who met the diagnostic criteria for severe malaria were treated with exchange
      transfusion 14 times according to a conventional anti-malarial treatment. This
      study evaluated the efficacy of exchange transfusion for severe imported
      falciparum malaria. METHODS: Clinical data of severe imported falciparum malaria
      patients admitted to the intensive care unit (ICU) of Nantong Third People's
      Hospital from January 2007 to December 2016 were investigated in this
      retrospective study. Patients were divided into the intervention group, which
      received exchange transfusion, and the control group. This study assessed
      parasite clearance and outcomes of the two groups, and levels of erythrocytes,
      haemoglobin, platelets, coagulation, liver function, lactate, C-reactive protein,
      and procalcitonin, before and after exchange transfusion in the intervention
      group. RESULTS: There was no significant difference in the severity of admitted
      patients. Exchange transfusion was successfully applied 14 times in the
      intervention group. Differences in the levels of erythrocytes, haemoglobin and
      platelets did not reach statistical significance. Exchange transfusion improved
      coagulation, liver function, lactic acid, C-reactive protein, and procalcitonin.
      No differences were observed in parasite clearance, ICU and hospital length of
      stay, in-hospital mortality, and costs of hospitalization between the two groups.
      CONCLUSION: Exchange transfusion as adjunctive therapy for severe malaria was
      observed to be safe in this setting. Exchange transfusion can improve liver
      function and coagulation and reduce inflammation, but it failed to improve
      parasite clearance and the outcomes of severe imported falciparum malaria in this
      case series.

PMID- 29338721
TI  - Infectious keratoconjunctivitis in semi-domesticated Eurasian tundra reindeer
      (Rangifer tarandus tarandus): microbiological study of clinically affected and
      unaffected animals with special reference to cervid herpesvirus 2.
AB  - BACKGROUND: Infectious keratoconjunctivitis (IKC) is one of the most common
      ocular diseases in ruminants worldwide. In addition to keratitis and
      conjunctivitis, animals with IKC can develop uveitis, corneal ulcer, and in
      severe cases, blindness. The bacteria Moraxella spp. has been described as the
      primary causative agent of infectious bovine keratoconjunctivitis (IBK) in cattle
      (Bos taurus), while Chlamydia spp. and Mycoplasma conjunctivae are considered the
      main causative agents of IKC in sheep (Ovis aries). Previous studies indicated
      cervid herpesvirus 2 (CvHV2) as the primary causative agent of IKC in semi
      domesticated reindeer (Rangifer tarandus tarandus). The aim of the study was to
      investigate the presence and prevalence of potential pathogens for IKC in
      reindeer, and compare the ocular microbiota of animals with IKC, with apparently
      healthy animals. RESULTS: Semi-domesticated reindeer (n = 341), with (n = 108) or
      without (n = 113) ocular clinical signs, or with no information on clinical
      status (n = 120), were sampled in Norway, Sweden and Finland in 2010-2014.
      Seroprevalence was 37.4% for alphaherpesvirus (95/254), 3.8% for gammaherpesvirus
      (8/211) and 7.1% for pestivirus (15/211) (ELISA). PCR analyses of conjunctival
      swab samples revealed a prevalence of 28.5% for CvHV2 (57/200), 11.9% for
      Chlamydiaceae (16/135) and 1.0% for M. conjunctivae (2/197). Bacteriological
      cultivation of 202 conjunctival swab samples revealed bacterial growth from 75.2%
      of the samples, with Moraxella spp. being isolated from 21.6% (11/51) of the
      animals with and 5.6% (5/84) without ocular clinical signs. A significant
      association (p < 0.001) existed between the presence of clinical signs of IKC and
      CvHV2 DNA in the affected eyes, an association that was not present for other
      microorganisms. CONCLUSIONS: These results support the hypothesis that CvHV2 is
      the primary agent of IKC in semi-domesticated reindeer in Fennoscandia, with
      Moraxella bovoculi being a secondary candidate, since it was isolated in two
      different outbreaks of IKC. Further studies should be carried out to better
      understand the infection biology and the pathogenesis of IKC in reindeer.

PMID- 29338722
TI  - Development and pilot evaluation of a clinic-based mHealth app referral service
      to support adult cancer survivors increase their participation in physical
      activity using publicly available mobile apps.
AB  - BACKGROUND: Participation in regular physical activity holds key benefits for
      cancer survivors, yet few cancer survivors meet physical activity
      recommendations. This study aimed to develop and pilot test a mHealth app
      referral service aimed at assisting cancer survivors to increase their physical
      activity. In particular, the study sought to examine feasibility and
      acceptability of the service and determine preliminary efficacy for physical
      activity behaviour change. METHODS: A systematic search identified potentially
      appropriate Apple (iOS) and Android mHealth apps. The apps were audited regarding
      the type of physical activity encouraged, evidence-based behavioural strategies
      and other characteristics, to help match apps to users' preferences and
      characteristics. A structured service was devised to deliver the apps and
      counselling, comprising two face-to-face appointments with a mid-week phone or
      email check-up. The mHealth app referral service was piloted using a pre-post
      design among 12 cancer survivors. Participants' feedback regarding the service's
      feasibility and acceptability was sought via purpose-designed questionnaire, and
      analysed using inductive thematic analysis and descriptive statistics. Change in
      physical activity was assessed using a valid and reliable self-report tool and
      analysed using paired t-tests. In line with recommendations for pilot studies,
      confidence intervals and effect sizes were reported to aid interpretation of
      clinical significance, with an alpha of 0.2 used to denote statistical
      significance. RESULTS: Of 374 mHealth apps identified during the systematic
      search, 54 progressed to the audit (iOS = 27, Android = 27). The apps
      consistently scored well for aesthetics, engagement and functionality, and
      inconsistently for gamification, social and behaviour change features. Ten
      participants completed the pilot evaluation and provided positive feedback
      regarding the service's acceptability and feasibility. On average, participants
      increased their moderate-vigorous physical activity by 236 min per week (d =
      0.73; 95% CI = -49 to 522; p = 0.09). CONCLUSION: This study offered initial
      evidence that a mHealth app referral service for cancer survivors is feasible and
      acceptable and may increase physical activity levels. The large increase in
      physical activity is promising, but should be interpreted with caution given the
      small sample size and lack of control group. Further research is warranted on a
      larger scale to investigate generalisability, long-term compliance and
      application in clinical settings.

PMID- 29338723
TI  - Preventing suicidal behaviours with a multilevel intervention: a cluster
      randomised controlled trial.
AB  - BACKGROUND: In the context of the recent surge in community based multilevel
      interventions for suicide prevention, all of which show promising results, we
      discuss the implications of the findings of such an intervention designed for and
      implemented in New Zealand. The multi-level intervention for suicide prevention
      in New Zealand (MISP-NZ) was a cluster randomised controlled community
      intervention trial involving eight hospital regions matched into four pairs and
      randomised to either the intervention or practice as usual (the control).
      Intervention regions received 25 months of interventions (01 June 2010 to 30 June
      2012) including: 1) training in recognition of suicide risk factors; 2) workshops
      on mental health issues; 3) community based interventions (linking in with
      community events); and 4) distribution of print material and information on web
      based resources. RESULTS: There was no significant difference between the change
      in rate of suicidal behaviours (ISH or self-inflicted deaths) in the intervention
      group compared with the control group (rate ratio = 1.07, 95% CI 0.82, 1.38).
      CONCLUSIONS: This study did not provide substantive evidence that the MISP-NZ
      intervention had an effect on suicidal behaviours raising important questions
      about the potential effectiveness of the multilevel intervention model for
      suicide prevention for all countries. Although a range of factors may account for
      this unanticipated finding, including inadequate study power, differences in
      design and intervention focus, and country-specific contextual factors, it is
      possible that the effectiveness of the multilevel intervention model for reducing
      suicidal behaviours may have been overstated. TRIAL REGISTRATION: This trial was
      retrospectively registered on 11 April 2013. ACTRN12613000399796 .

PMID- 29338724
TI  - Development and validation of HPTLC fingerprints of three species of Alpinia with
      biomarker Galangin.
AB  - BACKGROUND: Alpinia galanga (L.) Willd. commonly called as Rasna, Greater
      galangal or Kulinjan is a medicinally important rhizome used in Indian
      traditional system of medicine to cure a number of ailments. A. galanga is the
      main source of a galangin -a medicinally important flavanol which has a number of
      pharmacological properties viz. anti-mutagenic, and anti-inflammatory. Due to the
      high demand for the rhizome of A. galanga traders are now substituting it with
      rhizomes of A. calcarata and A. officinarum. METHODS: The present study aims to
      develop high performance thin layer chromatographic (HPTLC) fingerprinting of A.
      galanga with its adulterants or substitutes and to quantify bioactive galangin
      present thereof. Methanolic extracts were obtained from rhizomes of the three
      species of Alpinia used for HPTLC analysis using silica gel 60 F254 plates and
      hexane: ethyl acetate: acetic acid (6.2: 2.8: 1.0 v/v/v); the densitometric
      analysis was performed at 272 nm. RESULTS: By comparison of Rf values and of the
      spectra of the bands with those of the standard galangin was identified in all
      three samples. HPTLC quantitative analysis of the methanolic extracts showed the
      decline trend in the quantity of the galangin in the three species of Alpinia as
      A. galanga (7.67 +/- 0.36 mg/g) > A. officinarum (5.77 +/- 0.71 mg/g) > A.
      calcarata (4.31 +/- 0.44 mg/g). The HPTLC method was validated using
      International Conference on Harmonization (ICH) guidelines. The HPTLC method
      showed good linearity, recovery and high precision of biomarker. CONCLUSIONS:
      Rapid and reproducible method is useful for routine analysis of galangin and
      quality control of Alpinia galangal along with its adulterants or substitutes.

PMID- 29338725
TI  - Herbal formula YGJDSJ inhibits anchorage-independent growth and induces anoikis
      in hepatocellular carcinoma Bel-7402 cells.
AB  - BACKGROUND: Based on clinical medications and related studies, we established a
      Yang-Gan Jie-Du Sang-Jie (YGJDSJ) herbal formula for hepatocarcinoma treatment.
      In present study, we evaluated the anti-cancer potential of YGJDSJ on suspension
      grown human hepatocellular carcinoma Bel-7402 cells. METHODS: Bel-7402 cells were
      cultured in poly(2-hydroxyethyl methacrylate) (poly-HEMA) coated plates and
      treated with YGJDSJ. Anchorage-independent cell growth was detected by cell
      Counting Kit-8 (CCK-8) assay and soft agar colony formation assay. Anoikis was
      detected by ethdium homodimer-1 (EthD-1) staining and flow cytometry analysis.
      Caspases activities were detected by the cleavage of chromogenic substrate.
      Reactive oxygen species (ROS) was detected by 2',7'-dichlorofluorescin diacetate
      (DCFH-DA) staining. Protein expression and phosphorylation was identified by
      western blot. Protein expression was knocked-down by siRNA. RESULTS: YGJDSJ
      inhibited the proliferation of Bel-7402 cells in poly-HEMA coated plates and
      anchorage-independent growth of Bel-7402 cells in soft agar. YGJDSJ also induced
      anoikis in Bel-7402 cells as indicated by EthD-1 staining and flow cytometry
      analysis. YGJDSJ activated caspase-3, - 8, and - 9 in suspension-grown Bel-7402
      cells. The pan-caspase inhibitor Z-VAD-FMK significantly abrogated the effects of
      YGJDSJ on anoikis in suspension-grown Bel-7402 cells. In addition, YGJDSJ
      increased ROS in suspension-grown Bel-7402 cells. The ROS scavenger N-acetyl-L
      cysteine (NAC) partially attenuated YGJDSJ-induced activation of caspase-3, - 8
      and - 9 and anoikis in suspension-grown Bel-7402 cells. Furthermore, YGJDSJ
      inhibited expression and phosphorylation of protein tyrosine kinase 2 (PTK2) in
      suspension-grown Bel-7402 cells. Over-expression of PTK2 significantly abrogated
      YGJDSJ induced anoikis. CONCLUSIONS: YGJDSJ inhibits anchorage-independent growth
      and induce caspase-mediated anoikis in Bel-7402 cells, and may relate to ROS
      generation and PTK2 downregulation.

PMID- 29338726
TI  - A case of blackwater fever with persistent Plasmodium falciparum parasitaemia
      detected by PCR after artemether-lumefantrine treatment.
AB  - BACKGROUND: Blackwater fever is a complication of malaria infection consisting of
      a syndrome of febrile intra-vascular haemolysis with severe anaemia and
      intermittent passage of dark-red to black colour urine. Despite numerous reports
      and studies of this condition, its pathogenesis remains incompletely understood.
      CASE PRESENTATION: This report describes a case of classic blackwater fever in a
      returning traveller, without prior history of malaria infection nor usage of anti
      malarial prophylaxis, treated with two courses of oral artemether-lumefantrine
      combination therapy. Unusual persistence of submicroscopic Plasmodium falciparum
      parasitaemia was detected by PCR for 18 days after initiation of treatment.
      CONCLUSION: To the authors' knowledge this is the first reported occurrence of a
      case of blackwater fever associated with prolonged submicroscopic parasitaemia.
      This unusual case challenges the current knowledge of the pathogenesis of this
      condition and opens questions that may have important diagnostic and treatment
      implications.

PMID- 29338727
TI  - Mendelian randomization analysis to assess a causal effect of haptoglobin on
      macroangiopathy in Chinese type 2 diabetes patients.
AB  - BACKGROUND: Haptoglobin (Hp) functions as an antioxidant by binding with
      haemoglobin. We investigated whether serum Hp has a causal effect on
      macroangiopathy via Mendelian randomization (MR) analysis with common variants of
      the Hp gene in Chinese patients with type 2 diabetes. METHODS: A total of 5687
      type 2 diabetes patients were recruited and genotyped for the Hp gene. Clinical
      features and vascular imaging tests were applied to diagnose macroangiopathy. The
      association between common Hp genotypes and macroangiopathy was analyzed in the
      whole population. Serum Hp levels were measured by enzyme-linked immunosorbent
      assay in a subset of 935 patients. We individually analyzed the correlations
      among Hp levels, Hp genotypes and macroangiopathy. Further, 8-hydroxy-2'
      deoxyguanosine (8-OHdG), an oxidative marker of DNA damage, was examined to
      evaluate the levels of oxidative stress. RESULTS: Common Hp genotypes were
      correlated with macroangiopathy (OR = 1.140 [95% CI 1.005-1.293], P = 0.0410 for
      the Hp 1 allele). Serum Hp levels were associated with both common Hp genotypes
      (P = 3.55 * 10-31) and macroangiopathy (OR = 2.123 [95% CI 1.098-4.102], P =
      0.0252) in the subset of 935 patients. In the MR analysis, the directional trends
      of the observed and predicted relationships between common Hp genotypes and
      macroangiopathy were the same (OR 1.357 and 1.130, respectively). Furthermore,
      common Hp genotypes and Hp levels were associated with serum 8-OHdG levels (P =
      0.0001 and 0.0084, respectively). CONCLUSIONS: Our study provides evidence for a
      causal relationship between serum Hp levels and macroangiopathy in Chinese type 2
      diabetes patients by MR analysis.

PMID- 29338728
TI  - Re-evaluation of the definition of remission on the 17-item Hamilton Depression
      Rating Scale based on recovery in health-related quality of life in an
      observational post-marketing study.
AB  - BACKGROUND: Although a score of less than 7 for the 17-item Hamilton Depression
      Rating Scale (HAM-D17) has been widely adopted to define remission of depression,
      a full recovery from depression is closely related to the patient's quality of
      life as well. Accordingly, we re-evaluated this definition of remission using HAM
      D17 in comparison with the corresponding score for health-related quality of life
      (HRQOL) measured by the SF-36. METHODS: Using the data for depressive patients
      reported by GlaxoSmithKline K.K. (Study No. BRL29060A/863) in a post-marketing
      observational study of paroxetine, with a sample size of n = 722, multivariate
      logistic regression was performed with the HAM-D17 score as a dependent variable
      and with each of the eight domain scores of HRQOL (from the SF-36) transformed
      into a binominal form according to the national standard value for Japan. Then,
      area under curve of receiver operating characteristic analyses were conducted.
      Based on the obtained results, a multivariate analysis was performed using the
      HAM-D17 score in a binomial form with HAM-D17 as a dependent variable and with
      each of the eight HRQOL domain scores (SF-36) as binominalized independent
      variables. RESULTS: A cutoff value for the HAM-D17 score of 5 provided the
      maximum ROC-AUC at "0.864." The significantly associated scores of the eight
      HRQOL domains (SF-36) were identified for the HAM-D17 cutoff values of >=5 and
      <=4. The scores for physical functioning (odds ratio, 0.473), bodily pain
      (0.557), vitality (0.379), social functioning (0.540), role-emotion (0.265), and
      mental health (0.467) had a significant negative association with the HAM-D17
      score (p < 0.05), and HRQOL domain scores for HAM-D17 >= 5 were significantly
      lower compared with those for HAM-D17 <= 4. CONCLUSIONS: A cutoff value for HAM
      D17 of less than or equal to 4 was the best candidate for indicating remission of
      depression when the recovery of HRQOL is considered. Restoration of social
      function and performance should be considered equally important in assessing the
      adequacy of treatment for patients with depression.

PMID- 29338729
TI  - Computational study of the effects of arterial bifurcation on the temperature
      distribution during cryosurgery.
AB  - BACKGROUND: Thermally significant blood flows into locally cooled diseased
      tissues and warm them during cryosurgery so that the iceball is often hard to
      cover the whole diseased volume. This paper is aimed at investigating the effects
      of large arterial bifurcation on the temperature distribution during cryosurgery
      through simulation method. METHODS: A parametric geometry model is introduced to
      construct a close-to-real arterial bifurcation. The three-dimensional transient
      conjugate heat transfer between bifurcated artery and solid tissues with phase
      change during cryosurgery is performed by finite volume method. RESULTS: The
      discussion was then made on the effects of the relative position between
      cryoprobe and artery bifurcation, the inlet velocity of root artery and the
      layout of multiple cryoprobes on the temperature distribution and iceball
      evolution. The results show that the thermal interaction between blood flow and
      iceball growth near bifurcation is considerable complex. The thermal effects of
      bifurcation could modulate the iceball morphology, severely weaken its freezing
      volume and prevent the blood vessel from being frozen. CONCLUSION: The present
      work is expected to be valuable in optimizing cryosurgery scheme of the situation
      that the bifurcated artery is embedded into the disease tissue.

PMID- 29338730
TI  - Factors associated with HIV positive sero-status among exposed infants attending
      care at health facilities: a cross sectional study in rural Uganda.
AB  - BACKGROUND: East and South Africa contributes 59% of all pediatric HIV infections
      globally. In Uganda, HIV prevalence among HIV exposed infants was estimated at
      5.3% in 2014. Understanding the remaining bottlenecks to elimination of mother-to
      child transmission (eMTCT) is critical to accelerating efforts towards eMTCT.
      This study determined factors associated with HIV positive sero-status among
      exposed infants attending mother-baby care clinics in rural Kasese so as to
      inform enhancement of interventions to further reduce MTCT. METHODS: This was a
      cross-sectional mixed methods study. Quantitative data was derived from routine
      service data from the mother's HIV care card and exposed infant clinical chart.
      Key informant interviews were conducted with health workers and in-depth
      interviews with HIV infected mothers. Quantitative data was analyzed using Stata
      version 12. Logistic regression was used to determine factors associated with HIV
      sero-status. Latent content analysis was used to analyse qualitative data.
      RESULTS: Overall, 32 of the 493 exposed infants (6.5%) were HIV infected. Infants
      who did not receive ART prophylaxis at birth (AOR = 4.9, 95% CI: 1.901-13.051,
      p=0.001) and those delivered outside of a health facility (AOR = 5.1, 95% CI:
      1.038 - 24.742, p = 0.045) were five times more likely to be HIV infected than
      those who received prophylaxis and those delivered in health facilities,
      respectively. Based on the qualitative findings, health system factors affecting
      eMTCT were long waiting time, understaffing, weak community follow up system,
      stock outs of Neverapine syrup and lack of HIV testing kits. CONCLUSION:
      Increasing facility based deliveries and addressing underlying health system
      challenges related to staffing and availability of the required commodities may
      further accelerate eMTCT.

PMID- 29338731
TI  - Effective nationwide school-based participatory extramural program on adolescent
      body mass index, health knowledge and behaviors.
AB  - BACKGROUND: Adolescent obesity is a major public health concern. Open to all high
      school students regardless of weight status, HealthCorps is a nationwide program
      offering a comprehensive high school-based participatory educational program to
      indirectly address obesity. We tested a hypothesis that the HealthCorps program
      would decrease BMI z-scores among overweight or obese students, and reduce
      obesity rates, and evaluated its effects on health knowledge and behaviors.
      METHODS: HealthCorps aimed to improve student knowledge and behaviors regarding
      nutrition quality, physical activity, sleep, breakfast intake, and mental
      resilience. Participating students received through HealthCorps coordinators
      weekly or bi-weekly classroom lessons either for a semester or a year in addition
      to various during- and after-school health-promoting activities and mentorship.
      Self-reported height and weight were collected along with questionnaires
      assessing knowledge and behaviors during 2013-2014 academic year among 14
      HealthCorps-participating New York City high schools. This quasi experimental two
      arm pre-post trial included 611 HealthCorps and 221 comparison arm students for
      the analytic sample. Sex-specific analyses stratified by weight status were
      adjusted for age and Hispanic ethnicity with clustering effects of schools and
      students taken into account. RESULTS: HealthCorps female overweight/obese and
      obese student had a significant decrease in BMI z-scores (post-pre delta BMI z
      score = -0.16 (95%CI = (-0.26, -0.05), p = 0.004 for the former; and = -0.23 (
      0.44, -0.03), p = 0.028, for the latter) whereas comparison female counterparts
      did not. The HealthCorps students, but not the comparison students, had a
      significant increase for all knowledge domains except for the breakfast realm,
      and reported a greater number of significant behavior changes including fruit and
      vegetable intake and physical activities. CONCLUSIONS: The HealthCorps program
      was associated with reduced BMI z-score in overweight/obese and obese female
      adolescents, with enhanced health knowledge and behavior for both sexes. With its
      wide reach, this may be a promising program to help combat adolescent obesity in
      schools. TRIAL REGISTRATION: This study is registered as a clinical trial at the
      ClinicalTrials.gov registry with trial number NCT02277496 on September 10, 2014
      (Retrospectively registered).

PMID- 29338732
TI  - Transcriptional profile and Epstein-Barr virus infection status of laser-cut
      immune infiltrates from the brain of patients with progressive multiple
      sclerosis.
AB  - BACKGROUND: It is debated whether multiple sclerosis (MS) might result from an
      immunopathological response toward an active Epstein-Barr virus (EBV) infection
      brought into the central nervous system (CNS) by immigrating B cells. Based on
      this model, a relationship should exist between the local immune milieu and EBV
      infection status in the MS brain. To test this hypothesis, we analyzed expression
      of viral and cellular genes in brain-infiltrating immune cells. METHODS: Twenty
      three postmortem snap-frozen brain tissue blocks from 11 patients with
      progressive MS were selected based on good RNA quality and prominent immune cell
      infiltration. White matter perivascular and intrameningeal immune infiltrates,
      including B cell follicle-like structures, were isolated from brain sections
      using laser capture microdissection. Enhanced PCR-based methods were used to
      investigate expression of 75 immune-related genes and 6 EBV genes associated with
      latent and lytic infection. Data were analyzed using univariate and multivariate
      statistical methods. RESULTS: Genes related to T cell activation, cytotoxic cell
      mediated (or type 1) immunity, B cell growth and differentiation, pathogen
      recognition, myeloid cell function, type I interferon pathway activation, and
      leukocyte recruitment were found expressed at different levels in most or all MS
      brain immune infiltrates. EBV genes were detected in brain samples from 9 of 11
      MS patients with expression patterns suggestive of in situ activation of latent
      infection and, less frequently, entry into the lytic cycle. Comparison of data
      obtained in meningeal and white matter infiltrates revealed higher expression of
      genes related to interferongamma production, B cell differentiation, cell
      proliferation, lipid antigen presentation, and T cell and myeloid cell
      recruitment, as well as more widespread EBV infection in the meningeal samples.
      Multivariate analysis grouped genes expressed in meningeal and white matter
      immune infiltrates into artificial factors that were characterized primarily by
      genes involved in type 1 immunity effector mechanisms and type I interferon
      pathway activation. CONCLUSION: These results confirm profound in situ EBV
      deregulation and suggest orchestration of local antiviral function in the MS
      brain, lending support to a model of MS pathogenesis that involves EBV as
      possible antigenic stimulus of the persistent immune response in the central
      nervous system.

PMID- 29338733
TI  - Effect of metatarsal osteotomy and open lateral soft tissue procedure on sesamoid
      position: radiological assessment.
AB  - BACKGROUND: Incomplete sesamoid reduction is a potential risk factor for the
      recurrence of hallux valgus. The purpose of this study was to radiologically
      investigate changes in sesamoid position after chevron osteotomy and the open
      lateral soft tissue procedure. METHODS: Sixty-eight feet that underwent operative
      correction for hallux valgus deformity were reviewed consecutively. The hallux
      valgus angle (HVA), first to second intermetatarsal angle (IMA), tibial sesamoid
      position (TSP), distance of the fibular sesamoid (DFS), and translation of the
      metatarsal head (TMH) were evaluated preoperatively and at final follow-up.
      RESULTS: While most parameters were significantly decreased after surgery, no
      significant change in DFS (correction - 1.45 mm, p = 0.08) was noted. The
      difference between preoperative and postoperative TSP values (DeltaTSP) has a
      moderately positive correlation with difference in TMH values (DeltaTMH) (Rho
      0.475, p = .000). Other parameters were similarly correlated. CONCLUSIONS: First,
      metatarsal bone realignment reduced the sesamoid, but its position, relative to
      the second metatarsal axis (DFS), was unchanged. The sesamoid is reduced by the
      lateral translation of the first metatarsal but not by medial sesamoid migration.

PMID- 29338734
TI  - Comparing the benefits of chemoradiotherapy and chemotherapy for resectable stage
      III A/N2 non-small cell lung cancer: a meta-analysis.
AB  - BACKGROUND: Induction chemotherapy has been shown to improve survival of patients
      with stage III A/N2 (T1-3, N2, M0) non-small cell lung cancer (NSCLC), followed
      by resection, but the benefits of neoadjuvant radiotherapy still remain
      controversial. METHODS: PubMed, Embase, and Cochrane library databases were
      searched for relevant randomized controlled trials (RCTs) comparing the outcomes
      of induction chemoradiotherapy over induction chemotherapy, in patients with
      resectable stage IIIA/N2 NSCLC. Odds ratios (ORs) with corresponding 95%
      confidence intervals (95% CIs) were calculated using random- or fixed-effects
      model, and heterogeneity was assessed using I2 test. Publication bias was
      examined by funnel plots analysis. RESULTS: A total of three RCTs met the
      inclusion criteria of our meta-analysis. The pooled results demonstrated that, in
      comparison to induction chemotherapy, induction chemoradiotherapy has a
      significant benefit in tumor response, mediastinal downstaging, and pathological
      complete response of mediastinal lymph nodes. In addition, no more peri
      intervention mortality was detected in patients from chemoradiotherapy group, and
      a higher number of patients from this group had R0 resection. However, our
      results did not show any difference between overall survival and progression-free
      survival after 2, 4, and 6 years of follow-ups, in patients undergoing radiation
      therapy vs. induction chemotherapy. CONCLUSION: Preoperative chemoradiotherapy,
      as compared to induction chemotherapy alone, is associated with similar peri
      intervention mortality, a greater tumor response, mediastinal nodule downstaging,
      and rate of R0 resection, but does not improve survival of resectable stage
      IIIA/N2 NSCLC patients.

PMID- 29338735
TI  - Mental health service utilization is associated with retention in care among
      persons living with HIV at a university-affiliated HIV clinic.
AB  - BACKGROUND: Mental health (MH) comorbidities reduce retention in care for persons
      living with HIV (PLWH) and are associated with poor health outcomes. Optimizing
      retention in primary care is vital, as poor retention is associated with delayed
      receipt of antiretroviral (ARV) therapy, ARV non-adherence, and poor health
      outcomes, including failure to suppress viral load, decreased CD4 counts, and
      clinically significant ARV drug resistance. We hypothesized that MH service
      utilization would be associated with improved retention in care for patients with
      HIV and MH comorbidities. METHODS: This is a retrospective analysis of PLWH
      initiating outpatient HIV health care at a university-affiliated HIV clinic
      between January 2007 and December 2013. We examined the association between MH
      service utilization and retention in care, the outcome of interest, using
      univariate and multivariable logistic regression. RESULTS: Overall, 627 (84.4%)
      out of 743 patients were retained in care using the Health Resources & Services
      Administration HIV/AIDS Bureau (HRSA/HAB) metric. A multivariable model adjusted
      for several sociodemographic factors, MH comorbidities, and MH service
      utilization. The results suggest that lack of health insurance (public ORadj =
      0.3, p < 0.01; no insurance ORadj = 0.4, p < 0.01) and >= 3 MH comorbidities
      (ORadj = 0.3, P = 0.01) were associated with decreased retention in care.
      Conversely, older age (> 45 years, ORadj. = 1.6, p = 0.14) and >= 3 MH service
      utilization visits (ORadj. = 6.8, p < 0.01) were associated with increased
      retention in care. CONCLUSIONS: Even in the absence of documented MH
      comorbidities, improved retention in care was observed with increasing MH service
      utilization. In order to achieve the US-based National HIV/AIDS Strategy goal of
      90% retention in care for PLWH, MH service utilization should be considered along
      with other evidence-based interventions to improve retention for PLWH newly
      engaged in care.

PMID- 29338736
TI  - Spatial panorama of malaria prevalence in Africa under climate change and
      interventions scenarios.
AB  - BACKGROUND: Malaria is highly sensitive to climatic variables and is strongly
      influenced by the presence of vectors in a region that further contribute to
      parasite development and sustained disease transmission. Mathematical analysis of
      malaria transmission through the use and application of the value of the basic
      reproduction number (R0) threshold is an important and useful tool for the
      understanding of disease patterns. METHODS: Temperature dependence aspect of R0
      obtained from dynamical mathematical network model was used to derive the spatial
      distribution maps for malaria transmission under different climatic and
      intervention scenarios. Model validation was conducted using MARA map and the
      Annual Plasmodium falciparum Entomological Inoculation Rates for Africa. RESULTS:
      The inclusion of the coupling between patches in dynamical model seems to have no
      effects on the estimate of the optimal temperature (about 25  degrees C) for
      malaria transmission. In patches environment, we were able to establish a
      threshold value (about alpha = 5) representing the ratio between the migration
      rates from one patch to another that has no effect on the magnitude of R0. Such
      findings allow us to limit the production of the spatial distribution map of R0
      to a single patch model. Future projections using temperature changes indicated a
      shift in malaria transmission areas towards the southern and northern areas of
      Africa and the application of the interventions scenario yielded a considerable
      reduction in transmission within malaria endemic areas of the continent.
      CONCLUSIONS: The approach employed here is a sole study that defined the limits
      of contemporary malaria transmission, using R0 derived from a dynamical
      mathematical model. It has offered a unique prospect for measuring the impacts of
      interventions through simple manipulation of model parameters. Projections at
      scale provide options to visualize and query the results, when linked to the
      human population could potentially deliver adequate highlight on the number of
      individuals at risk of malaria infection across Africa. The findings provide a
      reasonable basis for understanding the fundamental effects of malaria control and
      could contribute towards disease elimination, which is considered as a challenge
      especially in the context of climate change.

PMID- 29338737
TI  - Transcriptome profiling of whitefly guts in response to Tomato yellow leaf curl
      virus infection.
AB  - BACKGROUND: Plant viruses in agricultural crops are of great concern worldwide,
      and over 75% of them are transmitted from infected to healthy plants by insect
      vectors. Tomato yellow leaf curl virus (TYLCV) is a begomovirus, which is the
      largest and most economically important group of plant viruses, transmitted by
      the whitefly Bemisia tabaci. The circulation of TYLCV in the insect involves
      complex insect-virus interactions, whereas the molecular mechanisms of these
      interactions remain ambiguous. The insect gut as a barrier for viral entry and
      dissemination is thought to regulate the vector specificity. However, due to its
      tiny size, information for the responses of whitefly gut to virus infection is
      limited. METHODS: We investigated the transcriptional response of the gut of B.
      tabaci Middle East-Asia Minor 1 species to TYLCV infection using Illumina
      sequencing. RESULTS: A total of 5207 differentially expressed genes (DEGs)
      between viruliferous and non-viruliferous whitefly guts were identified.
      Enrichment analyses showed that cargo receptor and ATP-binding cassette (ABC)
      transporters were enriched in DEGs, and might help the virus to cross gut
      barrier. TYLCV could perturb cell cycle and DNA repair as a possible result of
      its replication in the whitefly. Our data also demonstrated that TYLCV can
      activate whitefly defense responses, such as antimicrobial peptides. Meanwhile, a
      number of genes involved in intracellular signaling were activated by TYLCV
      infection. CONCLUSIONS: Our results reveal the complex insect-virus relationship
      in whitefly gut and provide substantial molecular information for the role of
      insect midguts in virus transmission.

PMID- 29338738
TI  - Rapid HIV disease progression following superinfection in an HLA-B*27:05/B*57:01
      positive transmission recipient.
AB  - BACKGROUND: The factors determining differential HIV disease outcome among
      individuals expressing protective HLA alleles such as HLA-B*27:05 and HLA-B*57:01
      remain unknown. We here analyse two HIV-infected subjects expressing both HLA
      B*27:05 and HLA-B*57:01. One subject maintained low-to-undetectable viral loads
      for more than a decade of follow up. The other progressed to AIDS in < 3 years.
      RESULTS: The rapid progressor was the recipient within a known transmission pair,
      enabling virus sequences to be tracked from transmission. Progression was
      associated with a 12% Gag sequence change and 26% Nef sequence change at the
      amino acid level within 2 years. Although next generation sequencing from early
      timepoints indicated that multiple CD8+ cytotoxic T lymphocyte (CTL) escape
      mutants were being selected prior to superinfection, < 4% of the amino acid
      changes arising from superinfection could be ascribed to CTL escape. Analysis of
      an HLA-B*27:05/B*57:01 non-progressor, in contrast, demonstrated minimal virus
      sequence diversification (1.1% Gag amino acid sequence change over 10 years), and
      dominant HIV-specific CTL responses previously shown to be effective in control
      of viraemia were maintained. Clonal sequencing demonstrated that escape variants
      were generated within the non-progressor, but in many cases were not selected. In
      the rapid progressor, progression occurred despite substantial reductions in
      viral replicative capacity (VRC), and non-progression in the elite controller
      despite relatively high VRC. CONCLUSIONS: These data are consistent with previous
      studies demonstrating rapid progression in association with superinfection and
      that rapid disease progression can occur despite the relatively the low VRC that
      is typically observed in the setting of multiple CTL escape mutants.

PMID- 29338739
TI  - Interventions for preventing or treating malnutrition in homeless problem
      drinkers: a systematic review.
AB  - BACKGROUND: Excessive drinking leads to poor absorption of nutrients and homeless
      problem-drinkers often have nutritionally inadequate diets. Depletion of
      nutrients such as vitamin B1 can lead to cognitive impairment, which can hinder
      efforts to reduce drinking or engage with services. This review aimed to assess
      effectiveness of interventions designed to prevent or treat malnutrition in
      homeless problem-drinkers. METHODS: We systematically searched nine electronic
      databases and 13 grey literature sources for studies evaluating interventions to
      improve nutrition in homeless populations, without regional or language
      restrictions. Screening for inclusion was done in duplicate. One reviewer
      extracted data and assessed risk of bias, and another checked the extractions.
      Primary outcomes were nutrition status/deficiency, liver damage, and cognitive
      function. Secondary outcomes included abstinence, comorbidities, resource use,
      acceptability and engagement with intervention. Results were synthesised
      narratively. RESULTS: We included 25 studies (2 Randomised Controlled Trials; 15
      uncontrolled before and after; 7 surveys; 1 case-control). Nine studies evaluated
      educational and support interventions, five food provision, and three supplement
      provision. Eight studies evaluated a combination of these interventions. No two
      interventions were the same, and all studies were at high risk of bias.
      Nutritional status (intake/ deficiency) were reported in 11 studies and liver
      function in one. Fruit and vegetable intake improved with some education and
      support interventions (n = 4 studies) but not others (n = 2). Vitamin supplements
      appeared to improve vitamin deficiency levels in the blood (n = 2). Free or
      subsidised meals (n = 4) and food packs (n = 1) did not always fulfil dietary
      needs, but were usually considered acceptable by users. Some multicomponent
      interventions improved nutrition (n = 3) but acceptability varied (n = 3). No
      study reported cost effectiveness. CONCLUSIONS: The evidence for any one
      intervention for improving malnutrition in homeless problem-drinkers was based on
      single studies at high risk of bias. Various food and supplement provision
      interventions appear effective in changing nutritional status in single studies.
      Educational and multicomponent interventions show improved nutritional behaviour
      in some studies but not others. Further better quality evidence is required
      before these interventions can be recommended for implementation. Any future
      studies should seek the end user input in their design and conduct. TRIAL
      REGISTRATION: Registered with PROSPERO: CRD42015024247 .

PMID- 29338740
TI  - Is sweat testing for cystic fibrosis feasible in patients with down syndrome?
AB  - BACKGROUND: Recurrent airway infections are common in patients with Down's
      syndrome (DS). Hence, ruling out Cystic Fibrosis (CF) in these patients is often
      required. In the past, the value of sweat testing - the gold standard to diagnose
      CF - has been questioned in DS as false positive results have been reported.
      However, these reports are based on measurements of sweat osmolality or sodium
      concentrations, not chloride concentrations. This study analyses sweat secretion
      rate and chloride concentration in sweat samples of patients with DS in
      comparison to healthy controls. METHODS: We assessed sweat samples in 16 patients
      with DS and 16 healthy controls regarding sweat secretion rate (SSR) and sweat
      chloride concentration. RESULTS: All measured chloride concentrations were within
      the normal range. The chloride concentrations were slightly, but not
      significantly lower in patients with DS (15,54 mmol/l (+/-4,47)) compared to
      healthy controls (18,31 mmol/l (+/-10,12)). While no gender gap in chloride
      concentration could be found, chloride concentration increased with age in both
      groups. Insufficient sweat was collected in 2 females with DS (12.5% of the study
      group) but not in an individual of the control group. A significant lower sweat
      secretion rate was found in the DS group (27,6 MUl/30 min (+/- 12,18)) compared
      to the control group (42,7 MUl/30 min (+/- 21,22)). In a sub-analysis, female
      patients produced significantly less sweat (20,8 +/- 10,6 MUl/30 min) than male
      patients with DS (36,4 +/- 7,8 MUl/30 min), which accounts for the difference
      between patients and controls. Furthermore, while the sweating secretion rate
      increased with age in the control group, it did not do so in the DS group. Once
      again this was due to female patients with DS, who did not show a significant
      increase of sweat secretion rate with age. CONCLUSIONS: Sweat chloride
      concentrations were within the normal range in patients with DS and therefore
      seem to be a reliable tool for testing for CF in these patients. Interestingly,
      we found a reduced sweat secretion rate in the DS group. Whether the last one has
      a functional and clinical counterpart, possibly due to a disturbed
      thermoregulation in DS patients, requires further investigation.

PMID- 29338741
TI  - Knowledge and practices of general practitioners at district hospitals towards
      cervical cancer prevention in Burundi, 2015: a cross-sectional study.
AB  - BACKGROUND: Well-organized screening and treatment programmes are effective to
      prevent Invasive Cervical Cancer (ICC) in LMICs. To achieve this, the World
      Health Organization (WHO) recommends the involvement of existing health personnel
      in casu doctors, nurses, midwives in ICC prevention. A necessary precondition is
      that health personnel have appropriate knowledge about ICC. Therefore, to inform
      policy makers and training institutions in Burundi, we documented the knowledge
      and practices of general practitioners (GPs) at district hospital level towards
      ICC control. METHODS: A descriptive cross-sectional survey was conducted from
      February to April, 2015 among all GPs working in government district hospitals. A
      structured questionnaire and a scoring system were used to assess knowledge and
      practices of GPs. RESULTS: The participation rate was 58.2%. Majority of GPs
      (76.3%) had appropriate knowledge (score > 70%) on cervical cancer disease; but
      some risk factors were less well known as smoking and the 2 most important
      oncogenic HPV. Only 8.4% of the participants had appropriate knowledge on ICC
      prevention: 55% of the participants were aware that HPV vaccination exists and
      48.1% knew cryotherapy as a treatment method for CIN. Further, 15.3% was aware of
      VIA as a screening method. The majority of the participants (87%) never or rarely
      propose screening tests to their clients. Only 2 participants (1.5%) have already
      performed VIA/VILI. Wrong thoughts were also reported: 39.7% thought that CIN
      could be treated with radiotherapy; 3.1% thought that X-ray is a screening
      method. CONCLUSION: In this comprehensive assessment, we observed that Burundian
      GPs have a very low knowledge level about ICC prevention, screening and
      treatment. Suboptimal practices and wrong thoughts related to ICC screening and
      treatments have also been documented. We therefore recommend an adequate pre- and
      in-service training of GPs and most probably nurses on ICC control before setting
      up any public health intervention on ICC control.

PMID- 29338742
TI  - M2-polarized tumor-associated macrophages facilitated migration and epithelial
      mesenchymal transition of HCC cells via the TLR4/STAT3 signaling pathway.
AB  - BACKGROUND: M2-polarized macrophages are tumor-associated-macrophages (TAMs),
      which are important contents of tumor-infiltrating immune cells. Toll-like
      receptor 4 (TLR4) is a molecular biomarker of tumor aggressiveness and poor
      prognosis. Toll-like receptors (TLRs) have important roles in the immune system
      and M2-polarized macrophages. However, the effects of TLR4 on M2-polarized
      macrophages in hepatocellular carcinoma (HCC) are unknown. Here, TLR4 expressed
      on HCC cells mediates the pro-tumor effects and mechanisms of M2-polarized
      macrophages. METHODS: THP-1 cells were induced to differentiate into M2-like
      macrophages through treatments with IL-4, IL-13, and phorbol myristate acetate
      (PMA). We used the HCC cell lines SMMC-7721 and MHCC97-H cultured in conditioned
      medium from M2-like macrophages (M2-CM) to investigate the migration potential of
      HCC cells and epithelial-mesenchymal transition (EMT)-associated molecular
      genetics. Signaling pathways that mediated M2-CM-promoted HCC migration were
      detected using western blotting. RESULTS: HCC cells cultured with M2-CM displayed
      a fibroblast-like morphology, an increased metastatic capability, and expression
      of EMT markers. TLR4 expression was markedly increased in M2-CM-treated HCC
      cells. TLR4 overexpression promoted HCC cell migration, and a TLR4-neutralizing
      antibody markedly inhibited HCC EMT in cells cultured with M2-CM. Furthermore,
      the TLR4/(signal transducer and activator of transcription 3 (STAT3) signaling
      pathway contributed to the effects of M2-CM on HCC cells. CONCLUSIONS: Taken
      together, M2-polarized macrophages facilitated the migration and EMT of HCC cells
      via the TLR4/STAT3 signaling pathway, suggesting that TLR4 may be a novel
      therapeutic target. These results improve our understanding of M2-polarized
      macrophages.

PMID- 29338743
TI  - The prospective and concurrent effect of exercise on health related quality of
      life in older adults over a 3 year period.
AB  - BACKGROUND: It is not clear whether socioeconomic status influences health
      outcomes among older adults through its effect on physical activity. The aim of
      this study was to assess the effect of sex and neighborhood socio-economic status
      on the change in health related quality of life (HR-QOL) as a function of
      physical activity over a three-year period. METHODS: This cohort study included
      French-speaking community-dwelling older adults recruited in primary care
      practices in the province of Quebec and participating in the 'Etude sur la Sante
      des Aines' (ESA)-Services study on the health of the elderly. Primary care
      practices were recruited through participating general practitioners (GPs)
      working full-time in the health administrative region. A stratified sample was
      comprised of various types of primary care practices (family medicine group,
      local community health services centers, primary care practices with less than 3
      GPs, and with at least 3 GPs). In this study sample, 967 participants with scores
      >=26 on the Mini Mental State Examination (MMSE) were included and followed for 3
      years to study HR-QOL as a function of reported exercise at baseline and follow
      up, controlling for study variables. Analyses were also carried out to study the
      effect of change in reported exercise at follow-up with respect to baseline and
      categorised as follows: no change, decrease in exercise and increase in exercise.
      The interaction terms area of residence socio-economic status*exercise and
      sex*exercise, were tested. RESULTS: Exercise at baseline did not significantly
      predict HR-QOL at follow-up when adjusting for all other study variables.
      Exercise at follow-up was cross-sectionally associated with follow-up HR-QOL.
      Participants reporting never exercising and those reporting a decrease in
      exercise reported a lower HR-QOL at follow-up, when controlling for all other
      study variables. There was no interaction between exercise and sex and
      socioeconomic status. CONCLUSIONS: For healthy ageing, maintaining and increasing
      physical activity throughout the years is necessary for improved HR-QOL. Past
      physical activity does not confer protection against future decline of HR-QOL.
      Future research should focus on potential moderating and mediating psycho-social
      barriers associated with exercising in older age populations.

PMID- 29338744
TI  - New insights in the relative radiobiological effectiveness of proton irradiation.
AB  - BACKGROUND: Proton radiotherapy is a form of charged particle therapy that is
      preferentially applied for the treatment of tumors positioned near to critical
      structures due to their physical characteristics, showing an inverted depth-dose
      profile. The sparing of normal tissue has additional advantages in the treatment
      of pediatric patients, in whom the risk of secondary cancers and late morbidity
      is significantly higher. Up to date, a fixed relative biological effectiveness
      (RBE) of 1.1 is commonly implemented in treatment planning systems with protons
      in order to correct the physical dose. This value of 1.1 comes from averaging the
      results of numerous in vitro experiments, mostly conducted in the middle of the
      spread-out Bragg peak, where RBE is relatively constant. However, the use of a
      constant RBE value disregards the experimental evidence which clearly
      demonstrates complex RBE dependency on dose, cell- or tissue type, linear energy
      transfer and biological endpoints. In recent years, several in vitro studies
      indicate variations in RBE of protons which translate to an uncertainty in the
      biological effective dose delivery to the patient. Particularly for regions
      surrounding the Bragg peak, the more localized pattern of energy deposition leads
      to more complex DNA lesions. These RBE variations of protons bring the validity
      of using a constant RBE into question. MAIN BODY: This review analyzes how RBE
      depends on the dose, different biological endpoints and physical properties.
      Further, this review gives an overview of the new insights based on findings made
      during the last years investigating the variation of RBE with depth in the spread
      out Bragg peak and the underlying differences in radiation response on the
      molecular and cellular levels between proton and photon irradiation. Research
      groups such as the Klinische Forschergruppe Schwerionentherapie funded by the
      German Research Foundation (DFG, KFO 214) have included work on this topic and
      the present manuscript highlights parts of the preclinical work and summarizes
      the research activities in this context. SHORT CONCLUSION: In summary, there is
      an urgent need for more coordinated in vitro and in vivo experiments that
      concentrate on a realistic dose range of in clinically relevant tissues like lung
      or spinal cord.

PMID- 29338745
TI  - Study of correlation between wall shear stress and elasticity in atherosclerotic
      carotid arteries.
AB  - OBJECTIVE: This paper presents the use of the texture matching method to measure
      the rabbit carotid artery elasticity value of the experimental group and control
      group respectively. It compares the experimental rabbits, when they are prompted
      by pathological histology to be at the period of carotid atherosclerosis fatty
      streaks and fiber plaques, with the control group. METHODS: We have used
      ultrasound linear array probe for scanning the rabbit carotid arteries. This
      allows us to obtain the wall shear stress (WSS) and the elasticity values in the
      atherosclerotic arteries. Using statistical analysis, we are able to clarify
      whether the texture matching method can diagnose atherosclerosis at the early
      stage. We also analyze the rabbit carotid artery elasticity and WSS values to
      make sure whether there is a correlation between both. Combining the texture
      matching method with the WSS quantitative analysis in the future can enable
      better prediction of the occurrence and development of atherosclerosis by using
      noninvasive medical imaging techniques. RESULTS: This study has confirmed that
      from the 2nd to the 10th week, with the development of atherosclerosis, the
      arterial WSS reduction has a negative correlation with the increasing of artery
      wall elasticity, which means that as the arterial WSS decreases the arterial wall
      becomes less elastic. Correlating shear stress with atherosclerosis can clarify
      that WSS can be used as one of the effective parameters of early diagnosis of
      atherosclerosis. CONCLUSION: In summary, we have found that the elasticity value
      can reflect the degree of atherosclerosis more objectively. Therefore, by using
      noninvasive imaging, the quantitative analysis of shear stress and combined with
      texture matching method can assist in the early diagnosis of atherosclerosis.

PMID- 29338746
TI  - Cost of diabetes mellitus in Africa: a systematic review of existing literature.
AB  - BACKGROUND: There is an increasing recognition that non communicable diseases
      impose large economic costs on households, societies and nations. However, not
      much is known about the magnitude of diabetes expenditure in African countries
      and to the best of our knowledge no systematic assessment of the literature on
      diabetes costs in Africa has been conducted. The aim of this paper is to capture
      the evidence on the cost of diabetes in Africa, review the methods used to
      calculate costs and identify areas for future research. METHODS: A desk search
      was conducted in Pubmed, Medline, Embase, and Science direct as well as through
      other databases, namely Google Scholar. The following eligibility criteria were
      used: peer reviewed English articles published between 2006 and 2016, articles
      that reported original research findings on the cost of illness in diabetes, and
      studies that covered at least one African country. Information was extracted
      using two data extraction sheets and results organized in tables. Costs presented
      in the studies under review are converted to 2015 international dollars prices
      (I$). RESULTS: Twenty six articles are included in this review. Annual national
      direct costs of diabetes differed between countries and ranged from I$3.5 billion
      to I$4.5 billion per annum. Indirect costs per patient were generally higher than
      the direct costs per patient of diabetes. Outpatient costs varied by study
      design, data source, perspective and healthcare cost categories included in the
      total costs calculation. The most commonly included healthcare items were drug
      costs, followed by diagnostic costs, medical supply or disposable costs and
      consultation costs. In studies that reported both drug costs and total costs,
      drug costs took a significant portion of the total costs per patient. The highest
      burden due to the costs associated with diabetes was reported in individuals
      within the low income group. CONCLUSION: Estimation of the costs associated with
      diabetes is crucial to make progress towards meeting the targets laid out in
      Sustainable Development Goal 3 set for 2030. The studies included in this review
      show that the presence of diabetes leads to elevated costs of treatment which
      further increase in the presence of complications. The cost of drugs generally
      contributed the most to total direct costs of treatment. Various methods are used
      in the estimation of diabetes healthcare costs and the costs estimated between
      countries differ significantly. There is room to improve transparency and make
      the methodologies used standard in order to allow for cost comparisons across
      studies.

PMID- 29338747
TI  - Oxidative stress predicts cognitive decline with aging in healthy adults: an
      observational study.
AB  - BACKGROUND: Redox signaling, which can be assessed by circulating aminothiols,
      reflects oxidative stress (OS) status and has been linked to clinical
      cardiovascular disease and its risk factors. These, in turn, are related to
      executive function decline. OS may precede the pro-inflammatory state seen in
      vascular disease. The objective of this study is to investigate the association
      between aminothiol markers of OS and inflammation in cognitive decline,
      especially in the executive cognitive domain which is highly susceptible to
      cardiovascular risk factors and is an important predictor of cognitive
      disability. METHODS: The study design is that of a longitudinal cohort study
      within the setting of a large academic institution with participants being
      university employees (n = 511), mean age 49 years, 68% women, and 23% African
      American. These participants were followed for four consecutive years with a
      yearly cognitive assessment conducted using computerized versions of 15 cognitive
      tests. Peripheral cystine, glutathione, their disulfide derivatives, and C
      reactive protein (CRP) were measured. RESULTS: Lower levels of glutathione at
      baseline was associated with a decline in the executive domain over 4 years
      (covariate-adjusted relative risk (RR) for glutathione = 1.70 (95% CI = 1.02
      2.85), p = 0.04). Furthermore, a longitudinal decline in glutathione level was
      associated with a faster decline in the executive domain (p = 0.03). None of the
      other OS markers or CRP were linked to cognitive decline over 4 years.
      CONCLUSION: Increased OS reflected by decreased glutathione was associated with a
      decline in executive function in a healthy population. In contrast, inflammation
      was not linked to cognitive decline. OS may be an earlier biomarker that precedes
      the inflammatory phase of executive decline with aging.

PMID- 29338748
TI  - Finite element analysis of intramedullary nailing and double locking plate for
      treating extra-articular proximal tibial fractures.
AB  - BACKGROUND: Proximal tibia fractures are one of the most familiar fractures.
      Surgical approaches are usually needed for anatomical reduction. However, no
      single treatment method has been widely established as the standard care. Our
      present study aims to compare the stress and stability of intramedullary nails
      (IMN) fixation and double locking plate (DLP) fixation in the treatment of extra
      articular proximal tibial fractures. METHODS: A three-dimensional (3D) finite
      element model of the extra-articular proximal tibial fracture, whose 2-cm bone
      gap began 7 cm from the tibial plateau articular surface, was created fixed by
      different fixation implants. The axial compressive load on an adult knee during
      single-limb stance was imitated by an axial force of 2500 N with a distribution
      of 60% to the medial compartment, while the distal end was fixed effectively. The
      equivalent von Mises stress and displacement of the model was used as the output
      measures for analysis. RESULTS: The maximal equivalent von Mises stress value of
      the system in the IMN model was 293.23 MPa, which was higher comparing against
      that in the DLP fixation model (147.04 MPa). And the mean stress of the model in
      the IMN model (9.25 MPa) was higher than that of the DLP fixation system in terms
      of equivalent von Mises stress (EVMS) (P < 0.0001). The maximal value of
      displacement (sum) in the IMN system was 8.82 mm, which was lower than that in
      the DLP fixation system (9.48 mm). CONCLUSIONS: This study demonstrated that the
      stability provided by the locking plate fixation system was superior to the
      intramedullary nails fixation system and served as an alternative fixation for
      the extra-articular proximal tibial fractures of young patients.

PMID- 29338749
TI  - Interleukin-6 induces fat loss in cancer cachexia by promoting white adipose
      tissue lipolysis and browning.
AB  - BACKGROUND: Cancer cachexia is a progressive and multi-factorial metabolic
      syndrome characterized by loss of adipose tissue and skeletal muscle. White
      adipose tissue (WAT) lipolysis and white-to-brown transdifferentiation of WAT
      (WAT browning) are proposed to contribute to WAT atrophy in cancer cachexia.
      Chronic inflammation, mediated by cytokines such as tumor necrosis factor alpha
      (TNF-alpha) and interleukin-6 (IL-6), has been reported to promote cancer
      cachexia. However, whether chronic inflammation promotes cancer cachexia by
      regulating WAT metabolism and the underlying mechanism remains unclear. METHODS:
      In this study, we first analyzed the association between chronic inflammation and
      WAT metabolism in gastric and colorectal cancer cachectic patients. In cachectic
      mice treated with anti-IL-6 receptor antibody, we clarified whether WAT lipolysis
      and browning were regulated by IL-6. RESULTS: Clinical analyses showed positive
      significant association between serum IL-6 and free fatty acid (FFA) both in
      early- and late-stage cancer cachexia. However, serum TNF-alpha was positively
      associated with serum FFA in the early- but not late-stage cachexia. WAT
      lipolysis was increased in early- and late-stage cachexia, while WAT browning was
      detected only in late-stage cachexia. Anti-IL-6 receptor antibody inhibited WAT
      lipolysis and browning in cachectic mice. CONCLUSIONS: Based on these findings,
      we conclude that chronic inflammation (especially that mediated by IL-6) might
      promote cancer cachexia by regulating WAT lipolysis in early-stage cachexia and
      browning in late-stage cachexia.

PMID- 29338751
TI  - Evaluation of the effects of a designated program on illegal drug cessation among
      adolescents who experiment with drugs.
AB  - BACKGROUND: Studies indicate that adolescent-onset drug users experience a
      greater likelihood of dependence that continues into adulthood. The importance of
      early intervention was evident in treating adolescents before their substance use
      progressed. We examined the effectiveness of an intervention program that
      prevents students who experiment with drugs from reusing them. METHODS: The study
      was based on 10 out of 18 invited schools that were randomly assigned to either
      the intervention group (5 schools, n = 43) or the comparison group (5 schools, n
      = 41). The intervention group received an E-course program that comprised a main
      intervention course (12 sessions) and a booster course (2 sessions). By reducing
      the burden of teaching content during the 14 sessions, the in-class counselor had
      opportunities for face-to-face discussions with students on their ambivalence
      toward quitting illegal drugs. The comparison group received the conventional
      didactic drug prevention course (2 sessions). Outcomes in terms of stress
      management, refusal skills, pros of drug use, cons of drug use, and drug use
      resistance self-efficacy were measured via structured questionnaires conducted
      thrice: at baseline, after the main intervention sessions, and after the booster
      sessions. A linear mixed model (LMM) was employed to investigate the effects of
      time and groups on the outcome variables with group, time, and group * time as
      fixed effects. Subjects and schools were selected as random effects in order to
      consider both within-subject and within-school correlations. RESULTS: There was a
      significant group * time interaction with regard to stress management, refusal
      skills, pros of drug use, and drug use resistance self-efficacy, excluding cons
      of drug use. The intervention group displayed better stress management compared
      to the comparison group after the booster intervention. Similar between-group
      differences were identified in that the intervention group displayed better
      refusal skills and drug use resistance self-efficacy compared to that of the
      comparison group. The intervention group favored using drugs less (a decrease in
      the pros of drug use score) compared to the comparison group after the booster
      intervention. CONCLUSIONS: Our program provided an example of the results of
      early intervention among students who experiment with illegal drugs.

PMID- 29338752
TI  - Structural alteration of DNA induced by viral protein R of HIV-1 triggers the DNA
      damage response.
AB  - BACKGROUND: Viral protein R (Vpr) is an accessory protein of HIV-1, which is
      potentially involved in the infection of macrophages and the induction of the
      ataxia-telangiectasia and Rad3-related protein (ATR)-mediated DNA damage response
      (DDR). It was recently proposed that the SLX4 complex of structure-specific
      endonuclease is involved in Vpr-induced DDR, which implies that aberrant DNA
      structures are responsible for this phenomenon. However, the mechanism by which
      Vpr alters the DNA structures remains unclear. RESULTS: We found that Vpr unwinds
      double-stranded DNA (dsDNA) and invokes the loading of RPA70, which is a single
      stranded DNA-binding subunit of RPA that activates the ATR-dependent DDR. We
      demonstrated that Vpr influenced RPA70 to accumulate in the corresponding region
      utilizing the LacO/LacR system, in which Vpr can be tethered to the LacO locus.
      Interestingly, RPA70 recruitment required chromatin remodelling via Vpr-mediated
      ubiquitination of histone H2B. On the contrary, Q65R mutant of Vpr, which lacks
      ubiquitination activity, was deficient in both chromatin remodelling and RPA70
      loading on to the chromatin. Moreover, Vpr-induced unwinding of dsDNA
      coincidently resulted in the accumulation of negatively supercoiled DNA and
      covalent complexes of topoisomerase 1 and DNA, which caused DNA double-strand
      breaks (DSBs) and DSB-directed integration of proviral DNA. Lastly, we noted the
      dependence of Vpr-promoted HIV-1 infection in resting macrophages on
      topoisomerase 1. CONCLUSIONS: The findings of this study indicate that Vpr
      induced structural alteration of DNA is a primary event that triggers both DDR
      and DSB, which ultimately contributes to HIV-1 infection.

PMID- 29338750
TI  - Reperfusion therapy in acute ischemic stroke: dawn of a new era?
AB  - Following the success of recent endovascular trials, endovascular therapy has
      emerged as an exciting addition to the arsenal of clinical management of patients
      with acute ischemic stroke (AIS). In this paper, we present an extensive overview
      of intravenous and endovascular reperfusion strategies, recent advances in AIS
      neurointervention, limitations of various treatment paradigms, and provide
      insights on imaging-guided reperfusion therapies. A roadmap for imaging guided
      reperfusion treatment workflow in AIS is also proposed. Both systemic
      thrombolysis and endovascular treatment have been incorporated into the standard
      of care in stroke therapy. Further research on advanced imaging-based approaches
      to select appropriate patients, may widen the time-window for patient selection
      and would contribute immensely to early thrombolytic strategies, better
      recanalization rates, and improved clinical outcomes.

PMID- 29338753
TI  - Examining within- and across-day relationships between transient and chronic
      stress and parent food-related parenting practices in a racially/ethnically
      diverse and immigrant population : Stress types and food-related parenting
      practices.
AB  - BACKGROUND: Although prior research suggests that stress may play a role in
      parent's use of food-related parenting practices, it is unclear whether certain
      types of stress (e.g., transient, chronic) result in different food-related
      parenting practices. Identifying whether and how transient (i.e., momentary;
      parent/child conflict) and chronic (i.e., long-term; unemployment >6 months)
      sources of stress are related to parent food-related parenting practices is
      important with regard to childhood obesity. This is particularly important within
      racially/ethnically diverse parents who may be more likely to experience both
      types of stress and who have higher levels of obesity and related health
      problems. The current study examined the association between transient and
      chronic stressors and food-related parenting practices in a racially/ethnically
      diverse and immigrant sample. METHODS: The current study is a cross-sectional,
      mixed-methods study using ecological momentary assessment (EMA). Parents (mean
      age = 35; 95% mothers) of children ages 5-7 years old (n = 61) from six
      racial/ethnic groups (African American, American Indian, Hispanic, Hmong, Somali,
      White) participated in this ten-day in-home observation with families. RESULTS:
      Transient stressors, specifically interpersonal conflicts, had significant within
      day effects on engaging in more unhealthful food-related parenting practices the
      same evening with across-day effects weakening by day three. In contrast,
      financial transient stressors had stronger across-day effects. Chronic stressors,
      including stressful life events were not consistently associated with more
      unhealthful food-related parenting practices. CONCLUSIONS: Transient sources of
      stress were significantly associated with food-related parenting practices in
      racially/ethnically diverse and immigrant households. Chronic stressors were not
      consistently associated with food-related parenting practices. Future research
      and interventions may want to assess for transient sources of stress in parents
      and target these momentary factors in order to promote healthful food-related
      parenting practices.

PMID- 29338755
TI  - Hyperhomocysteinemia in bilateral anterior ischemic optic neuropathy after
      conventional coronary artery bypass graft: a case report.
AB  - BACKGROUND: The incidence of anterior ischemic optic neuropathy after coronary
      artery bypass graft procedures ranges from 1.3 to 0.25%. The mechanisms of
      anterior ischemic optic neuropathy after cardiovascular procedures remain
      undefined but many systemic and related-to-surgery risk factors could underlie
      anterior ischemic optic neuropathy. In this case, we report a rare presentation
      of a bilateral anterior ischemic optic neuropathy after coronary artery bypass
      graft and speculate on the preoperative hyperhomocysteinemia as an independent
      risk factor for anterior ischemic optic neuropathy. CASE PRESENTATION: A 56-year
      old white man, a tobacco smoker with type 2 diabetes and coronary artery disease,
      underwent a conventional coronary artery bypass graft with extracorporeal
      circulation. In spite of ongoing anti-aggregation, antithrombotic, and
      vasodilator therapy, 10 days after the surgery he complained of severe bilateral
      visual loss. Funduscopy and fluorescein angiography revealed a bilateral anterior
      ischemic optic neuropathy. Analysis of preoperative laboratory tests revealed
      hyperhomocysteinemia. CONCLUSION: Hyperhomocysteinemia could increase the risk of
      ocular vascular damage and bilateral ocular involvement in patients who have
      undergone conventional coronary artery bypass graft.

PMID- 29338754
TI  - Molecular and functional signatures in a novel Alzheimer's disease mouse model
      assessed by quantitative proteomics.
AB  - BACKGROUND: Alzheimer's disease (AD), the most common neurodegenerative disorder,
      is characterized by the deposition of extracellular amyloid plaques and
      intracellular neurofibrillary tangles. To understand the pathological mechanisms
      underlying AD, developing animal models that completely encompass the main
      features of AD pathologies is indispensable. Although mouse models that display
      pathological hallmarks of AD (amyloid plaques, neurofibrillary tangles, or both)
      have been developed and investigated, a systematic approach for understanding the
      molecular characteristics of AD mouse models is lacking. METHODS: To elucidate
      the mechanisms underlying the contribution of amyloid beta (Abeta) and tau in AD
      pathogenesis, we herein generated a novel animal model of AD, namely the AD-like
      pathology with amyloid and neurofibrillary tangles (ADLPAPT) mice. The ADLPAPT
      mice carry three human transgenes, including amyloid precursor protein,
      presenilin-1, and tau, with six mutations. To characterize the molecular and
      functional signatures of AD in ADLPAPT mice, we analyzed the hippocampal proteome
      and performed comparisons with individual-pathology transgenic mice (i.e.,
      amyloid or neurofibrillary tangles) and wild-type mice using quantitative
      proteomics with 10-plex tandem mass tag. RESULTS: The ADLPAPT mice exhibited
      accelerated neurofibrillary tangle formation in addition to amyloid plaques,
      neuronal loss in the CA1 area, and memory deficit at an early age. In addition,
      our proteomic analysis identified nearly 10,000 protein groups, which enabled the
      identification of hundreds of differentially expressed proteins (DEPs) in ADLPAPT
      mice. Bioinformatics analysis of DEPs revealed that ADLPAPT mice experienced age
      dependent active immune responses and synaptic dysfunctions. CONCLUSIONS: Our
      study is the first to compare and describe the proteomic characteristics in
      amyloid and neurofibrillary tangle pathologies using isobaric label-based
      quantitative proteomics. Furthermore, we analyzed the hippocampal proteome of the
      newly developed ADLPAPT model mice to investigate how both Abeta and tau
      pathologies regulate the hippocampal proteome. Because the ADLPAPT mouse model
      recapitulates the main features of AD pathogenesis, the proteomic data derived
      from its hippocampus has significant utility as a novel resource for the research
      on the Abeta-tau axis and pathophysiological changes in vivo.

PMID- 29338757
TI  - A rapid high-resolution method for resolving DNA topoisomers.
AB  - OBJECTIVE: Agarose gel electrophoresis has been the mainstay technique for the
      analysis of DNA samples of moderate size. In addition to separating linear DNA
      molecules, it can also resolve different topological forms of plasmid DNAs, an
      application useful for the analysis of the reactions of DNA topoisomerases.
      However, gel electrophoresis is an intrinsically low-throughput technique and
      suffers from other potential disadvantages. We describe the application of the
      QIAxcel Advanced System, a high-throughput capillary electrophoresis system, to
      separate DNA topoisomers, and compare this technique with gel electrophoresis.
      RESULTS: We prepared a range of topoisomers of plasmids pBR322 and pUC19, and a
      339 bp DNA minicircle, and compared their separation by gel electrophoresis and
      the QIAxcel System. We found superior resolution with the QIAxcel System, and
      that quantitative analysis of topoisomer distributions was straightforward. We
      show that the QIAxcel system has advantages in terms of speed, resolution and
      cost, and can be applied to DNA circles of various sizes. It can readily be
      adapted for use in compound screening against topoisomerase targets.

PMID- 29338756
TI  - Spatial access to restaurants and grocery stores in relation to frequency of home
      cooking.
AB  - BACKGROUND: Little is known about the relation between the neighbourhood food
      environment and home cooking. We explored the independent and combined
      associations between residential neighbourhood spatial access to restaurants and
      grocery stores with home cooking in European adults. METHODS: Data of 5076
      participants of the SPOTLIGHT study were collected across five European countries
      in 2014. Food retailers were classified into grocery stores (supermarkets and
      local food shops) and restaurants (full-service restaurants, fast food and take
      away restaurants, cafe/bars). We used multinomial logistic regression models to
      test the associations between tertiles of spatial access to restaurants and
      spatial to access grocery stores and the outcome 'frequency of home cooking'
      categorized into 0-3; 4-5; and 6-7 days/week. Additive interaction analysis was
      used to test the combined association between access to grocery stores and to
      restaurants with home cooking. RESULTS: Mean age was 52.3 years; most
      participants were women (55.5%) and completed higher education (53.8%). Residents
      with highest access to restaurants had a reduced likelihood of home cooking 6-7
      days/week (vs. 0-3 days/week) (relative risk ratio (RRR) 0.42; 95%CI = 0.23-0.76)
      when compared with lowest access to restaurants. No association was found for
      spatial access to grocery stores. Additive interaction analysis showed that
      individuals with medium access to grocery stores and highest access to
      restaurants had the lowest likelihood (RRR = 0.29, 95%CI = 0.10-0.84) of cooking
      6-7 days/week when compared to individuals with lowest access to restaurants and
      highest access to grocery stores. CONCLUSION: Greater neighbourhood spatial
      access to restaurants was associated with lower frequency of home cooking,
      largely independent of access to grocery stores.

PMID- 29338758
TI  - Vitamin D status and dental caries in healthy Swedish children.
AB  - Background: Vitamin D is crucial for mineralized tissue formation and
      immunological functions. The purpose of this study was to evaluate the
      association between vitamin D status and dental status in healthy children with
      vitamin D supplementation in infancy and at 6 years of age. Method: Eight-year
      old children who had participated in a vitamin D intervention project when they
      were 6 years old were invited to participate in a dental follow-up study. They
      had fair or darker skin complexion and represented two geographically distant
      parts of Sweden. 25-hydroxy vitamin D in serum had been measured at 6 years of
      age and after a 3-month intervention with 25, 10 or 2 (placebo) MUg of vitamin
      D<subscript>3</subscript> per day. Two years later, caries and enamel defects
      were scored, self-reported information on e.g., oral behavior, dietary habits and
      intake of vitamin D supplements was collected, and innate immunity peptide LL37
      levels in saliva and cariogenic mutant streptococci in tooth biofilm were
      analyzed. The outcome variables were caries and tooth enamel defects. Results:
      Dental status was evaluated in 85 of the 206 children in the basic intervention
      study. Low vitamin D levels were found in 28% at baseline compared to 11% after
      the intervention, and 34% reported continued intake of vitamin D supplements.
      Logistic regression supported a weak inverse association between vitamin D status
      at 6 years of age and caries 2 years later (odds ratio 0.96; p = 0.024) with
      minor attenuation after an adjustment for potential confounders. Multivariate
      projection regression confirmed that insufficient vitamin D levels correlated
      with caries and higher vitamin D levels correlated with being caries-free.
      Vitamin D status at 6 years of age was unrelated to enamel defects but was
      positively associated with saliva LL37 levels. Conclusion: An association between
      vitamin D status and caries was supported, but it was not completely consistent.
      Vitamin D status at 6 years of age was unrelated to enamel defects but was
      positively associated with LL37 expression. Trial registration: The basic
      intervention study was registered at ClinicalTrials.gov with register number
      NCT01741324  www.clinicaltrials.gov/ct2/show/NCT02347293 on November 26, 2012.

PMID- 29338759
TI  - Correction to: Avoidable waste related to inadequate methods and incomplete
      reporting of interventions: a systematic review of randomized trials performed in
      Sub-Saharan Africa.
AB  - CORRECTION: In the original publication [1] the last sentence in the last
      paragraph under 'Perspectives and implications' in the Discussions section needs
      to be removed. The correct version can be found in this Erratum.

PMID- 29338760
TI  - Increased Plasmodium chabaudi malaria mortality in mice with nutritional iron
      deficiency can be reduced by short-term adjunctive iron supplementation.
AB  - BACKGROUND: Iron deficiency is the most widespread nutrient deficiency and an
      important cause of developmental impairment in children. However, some studies
      have indicated that iron deficiency can also protect against malaria, which is a
      leading cause of childhood morbidity and mortality in large parts of the world.
      This has rendered interventions against iron deficiency in malaria-endemic areas
      controversial. METHODS: The effect of nutritional iron deficiency on the clinical
      outcome of Plasmodium chabaudi AS infection in A/J mice and the impact of
      intravenous iron supplementation with ferric carboxymaltose were studied before
      and after parasite infection. Plasma levels of the iron status markers hepcidin
      and fibroblast growth factor 23 were measured in animals surviving and succumbing
      to malaria, and accompanying tissue pathology in the liver and the spleen was
      assessed. RESULTS: Nutritional iron deficiency was associated with increased
      mortality from P. chabaudi malaria. This increased mortality could be partially
      offset by carefully timed, short-duration adjunctive iron supplementation.
      Moribund animals were characterized by low levels of hepcidin and high levels of
      fibroblast growth factor 23. All infected mice had extramedullary splenic
      haematopoiesis, and iron-supplemented mice had visually detectable intracellular
      iron stores. CONCLUSIONS: Blood transfusions are the only currently available
      means to correct severe anaemia in children with malaria. The potential of
      carefully timed, short-duration adjunctive iron supplementation as a safe
      alternative should be considered.

PMID- 29338761
TI  - Is total femoral replacement for non-oncologic and oncologic indications a safe
      procedure in limb preservation surgery? A single center experience of 22 cases.
AB  - BACKGROUND: Several surgical options for the reconstruction of massive bone
      defects have been described and include biologic methods with autografts and
      allografts, and the use of tumor endoprostheses (total femoral replacement, TFR).
      Several types of modular TFR are available, but nevertheless unpredictable
      outcomes and high complication rates have been described from most authors. The
      present study aims to compare results after TFR performed with modular total
      femur prosthesis MML (Fa. ESKA/Orthodynamics) in patients with and without
      malignant disease. METHODS: Retrospective chart review and functional
      investigation (Musculoskeletal Tumor Society (MSTS) score, Harris Hip Score
      (HHS), Oxford Knee Score (OKS), SF-12 Health Survey, and failure classification
      according to Henderson) of TFR cases from 1995 to 2011. Indications for TFR were
      malignant tumor resection from the femur (n = 9, Group A) or failure of a
      revision arthroplasty without history of malignant disease (n = 13, Group B).
      RESULTS: Thirty-six patients were treated during the study period, of whom 22
      could be investigated clinically after a mean follow-up of 63 months. Overall
      failure rate for TFR was 59.1%, leading to 38 surgical revisions. The most common
      failure mechanisms were Type I (soft tissue), followed by Type IV (infection) and
      Type III (mechanical failure). Mean MSTS score out of 30 was 13 (range 1-25),
      with significantly higher scores in Group A (mean 19, range 3-25) than Group B
      (mean 9, range 1-15). CONCLUSION: TFR is an established procedure to restore
      femoral integrity. However, complication rates are considerably high, and depend
      mainly on the age at initial reconstruction.

PMID- 29338762
TI  - Predictors of remission with etanercept-methotrexate induction therapy and loss
      of remission with etanercept maintenance, reduction, or withdrawal in moderately
      active rheumatoid arthritis: results of the PRESERVE trial.
AB  - BACKGROUND: The aim was to analyze characteristics that predict remission
      induction and subsequent loss of remission in patients with moderately active
      rheumatoid arthritis (RA) who received full-dose combination etanercept plus
      methotrexate induction therapy followed by reduced-dose etanercept or etanercept
      withdrawal. METHODS: Patients with Disease Activity Score based on 28-joint count
      (DAS28) >3.2 and <=5.1 received open-label etanercept 50 mg once weekly (QW) plus
      methotrexate for 36 weeks. Those who achieved DAS28 low disease activity by 36
      weeks were randomized to double-blind treatment with etanercept 50 mg or 25 mg QW
      plus methotrexate or placebo plus methotrexate for 52 weeks. All analyses were
      adjusted for the continuous baseline variables of their respective remission
      outcomes. RESULTS: Younger age, body mass index (BMI) <30 kg/m2, and lower Health
      Assessment Questionnaire (HAQ) score at baseline were significant predictors of
      week-36 remission (P < 0.05) based on DAS28, Simplified Disease Activity Index
      (SDAI), and Clinical Disease Activity Index (CDAI). Baseline DAS28, SDAI, and
      CDAI were significantly predictive of all three remission endpoints (P < 0.05).
      For all three treatments, the strongest predictors of loss of DAS28 remission
      included failure to achieve sustained remission (DAS28 < 2.6 at weeks 12, 20, 28,
      and 36) with induction therapy, higher DAS28/SDAI/CDAI at randomization and at 1
      month, increase in DAS28/SDAI/CDAI at 1 month, and increase in DAS28/CDAI/SDAI
      components and patient-reported outcomes (PROs) at 1 month. With the exception of
      not achieving sustained remission, very similar significant predictors were
      observed for loss of SDAI and CDAI remission. CONCLUSION: These findings suggest
      that patients with moderately active RA who are younger and have lower BMI, lower
      HAQ, and lower disease activity at baseline are most likely to achieve remission
      when receiving combination etanercept and methotrexate induction therapy. In
      addition, patients who fail to achieve sustained remission with induction therapy
      and those with worse disease activity and PROs at early time points after
      initiating maintenance therapy with a full-dose or reduced-dose etanercept
      methotrexate regimen or methotrexate monotherapy are most likely to lose
      remission across all treatment arms. These findings may help guide clinicians'
      decision-making as they treat patients to remission and beyond. TRIAL
      REGISTRATION: ClinicalTrials.gov, NCT00565409 . Registered on 28 November 2007.

PMID- 29338763
TI  - Sero-prevalence of HBsAg in naive HIV-infected patients in a rural locality of
      Cameroon.
AB  - OBJECTIVE: This study was performed in order to fill the gap of knowledge
      regarding sero-epidemiology of hepatitis B virus (HBV) amongst Human
      Immunodeficiency virus (HIV)-infected patients and to assess the risk factors
      associated with HBV co-infection in a rural locality of Cameroon. A retrospective
      and cross-sectional study was carried out from January 2008 to April 2014 within
      the Mfou District Hospital. Naive HIV-infected patients were enrolled in the
      study and tested for hepatitis B surface antigen (HBsAg). Preliminary pre
      therapeutic data essential for follow-up was collected from the participants.
      RESULTS: Overall, the sample size was constituted of 712 HIV-infected patients.
      The prevalence of HBsAg was 8.99%. A significant difference was observed in the
      proportion of HBsAg positive subjects with respect to the year of inclusion;
      higher proportions were observed between 2011 and 2014 (P-value = 0.007).
      Majority of HBV co-infected participants had severe immuno-suppression with CD4
      counts lower than 100 cells/uL as compared to HIV mono-infected population but
      the difference was not statistically significant. Our results confirm the high
      prevalence for HBV infection among HIV-infected patients in the Mfou District
      Hospital. These findings will enable stake holders to be better armed in the
      elimination of viral hepatitis as a public health problem.

PMID- 29338765
TI  - Infantile hypertrophic pyloric stenosis: a 4-year experience from two tertiary
      care centres in Cameroon.
AB  - OBJECTIVE: This study aimed to describe the clinical characteristics of patients
      with infantile hypertrophic stenosis, management and its outcome in two tertiary
      care centres in Cameroon. RESULTS: A total of 21 patients were included from the
      two centres. The mean age at presentation was 5.2 +/- 1.2 weeks, predominantly
      male with a male-to-female ratio of 4.25:1. The triad of vomiting, visible
      peristalsis and palpable mass was present in only 7 (33.3%) of the participants.
      The diagnosis was confirmed with ultrasounds in all participants. Ramstedt
      pyloromyotomy was done in all participants and in 9.5% of the participants it was
      complicated by intra-operative duodenal perforation whereas in the postoperative
      period the most common complications were vomiting (6, 28.6%), sepsis (2, 9.5%),
      and paralytic ileus (2, 9.5%). The mortality rate from the series is 9.5%.
      According to univariate logistic regression: severe dehydration [OR = 5.41, 95%
      CI = (3.11-6.97), p = 0.002], hypokalaemia [OR = 2.63, 95% CI = (1.02-5.91), p =
      0.042] and surgical site infection [OR = 3.12, 95% CI (1.22-5.64), p = 0.023]
      were the main predictors of mortality whereas postoperative hospital length of
      stay > 5 days was significantly associated with surgical site infection [OR =
      2.44, 95% CI = (1.12-6.44), p = 0.002] and postoperative nausea and vomiting [OR
      = 3.64, 95% CI = (1.18-6.64), p = 0.022].

PMID- 29338764
TI  - Cropping practices manipulate abundance patterns of root and soil microbiome
      members paving the way to smart farming.
AB  - BACKGROUND: Harnessing beneficial microbes presents a promising strategy to
      optimize plant growth and agricultural sustainability. Little is known to which
      extent and how specifically soil and plant microbiomes can be manipulated through
      different cropping practices. Here, we investigated soil and wheat root microbial
      communities in a cropping system experiment consisting of conventional and
      organic managements, both with different tillage intensities. RESULTS: While
      microbial richness was marginally affected, we found pronounced cropping effects
      on community composition, which were specific for the respective microbiomes.
      Soil bacterial communities were primarily structured by tillage, whereas soil
      fungal communities responded mainly to management type with additional effects by
      tillage. In roots, management type was also the driving factor for bacteria but
      not for fungi, which were generally determined by changes in tillage intensity.
      To quantify an "effect size" for microbiota manipulation, we found that about 10%
      of variation in microbial communities was explained by the tested cropping
      practices. Cropping sensitive microbes were taxonomically diverse, and they
      responded in guilds of taxa to the specific practices. These microbes also
      included frequent community members or members co-occurring with many other
      microbes in the community, suggesting that cropping practices may allow
      manipulation of influential community members. CONCLUSIONS: Understanding the
      abundance patterns of cropping sensitive microbes presents the basis towards
      developing microbiota management strategies for smart farming. For future
      targeted microbiota management-e.g., to foster certain microbes with specific
      agricultural practices-a next step will be to identify the functional traits of
      the cropping sensitive microbes.

PMID- 29338766
TI  - Identification of differentially expressed genes and pathways for intramuscular
      fat metabolism between breast and thigh tissues of chickens.
AB  - BACKGROUND: Intramuscular fat (IMF) is one of the important factors influencing
      meat quality, however, for chickens, the molecular regulatory mechanisms
      underlying this trait have not yet been clear. In this study, a systematic
      identification of differentially expressed genes (DEGs) and molecular regulatory
      mechanism related to IMF metabolism between Beijing-you chicken breast and thigh
      at 42 and 90 days of age was performed. RESULTS: IMF contents, Gene Ontology (GO)
      terms, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were analyzed,
      The results showed that both IMF contents in breast at 42 and 90 d were
      significantly lower (P < 0.05 or P < 0.01) than those in thigh. By microarray,
      515 common known DEGs and 36 DEGs related to IMF metabolism were identified
      between the breast and thigh at 42 and 90 d. Compared to thigh, the expression
      levels of PPARG had significantly down-regulated (P < 0.01) in breast, but the
      expression levels of RXRA and CEBPB had significantly up-regulated (P < 0.01).
      However, the expression levels of LPL, FABP4, THRSP, RBP7, LDLR, FABP3, CPT2 and
      PPARGC1A had significantly down-regulated in breast (P < 0.01), supporting that
      PPARG and its down-stream genes had the important regulatory function to IMF
      deposition. In addition, based on of DEGs, KEGG analysis revealed that PPAR
      signaling pathway and cell junction-related pathways (focal adhesion and ECM
      receptor interaction, which play a prominent role in maintaining the integrity of
      tissues), might contribute to the IMF metabolism in chicken. CONCLUSIONS: Our
      data had screened the potential candidate genes associated with chicken IMF
      metabolism, and imply that IMF metabolism in chicken is regulated and mediated
      not only by related functional genes and PPAR pathway, but also by others
      involved in cell junctions. These findings establish the groundwork and provide
      new clues for deciphering the molecular mechanisms underlying IMF deposition in
      poultry. Further studies at the translational and posttranslational level are now
      required to validate the genes and pathways identified here.

PMID- 29338767
TI  - Effect of exercise versus cognitive behavioural therapy or no intervention on
      anxiety, depression, fitness and quality of life in adults with previous
      methamphetamine dependency: a systematic review.
AB  - BACKGROUND: Methamphetamine (MA) is a highly addictive psychostimulant used by
      approximately 52 million people worldwide. Chronic MA abuse leads to detrimental
      physiological and neurological changes, as well as increases in anxiety and
      depression, and decreases in overall fitness and quality of life. Exercise has
      been reported to possibly reverse physiological and neurological damage caused by
      previous MA use, and to reduce anxiety and depression in this population. The aim
      of this systematic review was to identify, clinically appraise and synthesise the
      available evidence for the effectiveness of exercise, compared to cognitive
      behavioural therapy (CBT), standard care or no intervention, on decreasing
      anxiety and depression and improving fitness and quality of life in previous MA
      users. METHODS: Seven computerised databases were searched from inception to May
      2017, namely Scopus, Cochrane Library, PubMed/MEDLINE, PEDro, CINAHL, and
      ScienceDirect. Search terms included exercise, methamphetamine, fitness measures,
      depression, anxiety and quality of life. Randomised and non-randomised controlled
      or clinical trials and pilot studies, published in English, were considered for
      inclusion. Methodological quality was critically appraised according to the PEDro
      scale. Heterogeneity across studies regarding control groups and assessment
      intervals rendered meta analyses inappropriate for this review and results were
      thus described narratively using text and tables. RESULTS: Two hundred and fifty
      one titles were identified following the initial search, and 14 potentially
      relevant titles were selected and the abstracts reviewed. Three studies (two
      randomised controlled trials and one quasi-experimental pilot) were included,
      with an average PEDro score of 6.66. Exercise resulted in significantly lower
      depression and anxiety scores versus CBT (p = 0.001). Balance also significantly
      improved following exercise versus standard care (p < 0.001); as did vital
      capacity, hand-grip and one-leg stand with eyes closed. There were significant
      changes in all subdivisions of the Quality of Life Scale Questionnaire (p <
      0.05), except psychology (p = 0.227). CONCLUSIONS: Level II evidence suggests
      that exercise is effective in reducing anxiety and depression and improving
      fitness in previous MA users, and Level III-2 evidence suggests that exercise is
      beneficial for improving quality of life in this population. Overall recovery in
      previous MA dependents might be significantly enhanced by including exercise in
      the rehabilitation process. Further research is required to strengthen these
      conclusions and to inform policy and health systems effectively.

PMID- 29338769
TI  - Publication rate of abstracts presented at Japan Geriatrics Society Annual
      Meetings (2011-2012): a retrospective observational study.
AB  - OBJECTIVE: We aimed to determine the publication rate of abstracts presented at
      Japan Geriatrics Society Annual Meetings. Publication rates were determined by
      searching for full-text publications up to September 2017 in the MEDLINE
      database. Factors associated with publication were determined. RESULTS: In total,
      618 abstracts presented at Japan Geriatrics Society Annual Meetings (2011-2012)
      were included. Of those, 146 (23.6% [95% CI 20.3-27.0%]) were published in peer
      reviewed journals indexed in MEDLINE. The median time to publication was 13.0
      months (interquartile range 6.0-25.8 months). More than 90% were published within
      4 years. The publications appeared in 64 different journals, and 87.0% were
      published in English-language journals. Multivariable analysis revealed more
      frequent publication of oral presentations (25.4% vs 16.9% of poster
      presentations; adjusted OR 1.79 [95% CI 1.05-3.06]), randomized controlled trials
      (66.7% vs 22.8% for other study designs; adjusted OR 10.79 [95% CI 3.02-38.53])
      and studies with n >= 100 (28.7% vs 18.4% of studies with n < 100; adjusted OR
      1.97 [95% CI 1.32-2.95]). Because more than three-fourths of the abstracts
      presented at Japan Geriatrics Society Annual Meetings remained unpublished within
      5 years after the conferences, additional efforts may be needed to promote their
      publication.

PMID- 29338768
TI  - Binary-blend fibber-based capture assay of circulating tumor cells for clinical
      diagnosis of colorectal cancer.
AB  - BACKGROUND: In addition to conventional approaches, detecting and characterizing
      CTCs in patient blood allows for early diagnosis of cancer metastasis. METHODS:
      We blended poly(ethylene oxide) (PEO) into nylon-6 through electrospinning to
      generate a fibrous matbased circulating tumour cells (CTCs) assay. The contents
      of nylon-6 and PEO in the electrospun blend fibrous mats (EBFMs) were optimized
      to facilitate high cell-substrate affinity and low leukocyte adsorption. RESULTS:
      Compared with the IsoFlux System, a commercial instrument for CTC detection, the
      CTC assay of EBFMs exhibited lower false positive readings and high sensitivity
      and selectivity with preclinical specimens. Furthermore, we examined the clinical
      diagnosis accuracy of colorectal cancer, using the CTC assay and compared the
      results with those identified through pathological analyses of biopsies from
      colonoscopies. Our positive expressions of colorectal cancer through CTC
      detection completely matched those recognized through the pathological analyses
      for the individuals having stage II, III, and IV colorectal cancer. Nevertheless,
      two in four individuals having stage I colorectal cancer, recognized through
      pathological analysis of biopsies from colonoscopies, exhibited positive
      expression of CTCs. Ten individuals were identified through pathological analysis
      as having no colorectal tumours. Nevertheless, two of these ten individuals
      exhibited positive expression of CTCs. CONCLUSIONS: Thus, in this population, the
      low cost EBFMs exhibited considerable capture efficiency for the non-invasive
      diagnosis of colorectal cancer.

PMID- 29338770
TI  - Nonmedical prescription opioid use and illegal drug use: initiation trajectory
      and related risks among people who use illegal drugs in Vancouver, Canada.
AB  - OBJECTIVE: We investigated the prevalence of and risk factors associated with
      initiating nonmedical prescription opioid use (NMPOU) before and after illegal
      drugs using data from two linked cohort studies of street youth and adults who
      use illegal drugs in Vancouver, Canada. All participants who attended a study
      visit between 2013 and 2016 were eligible for the primary analyses. RESULTS:
      Among 512 youth and 833 adult participants, the prevalence of NMPOU was extremely
      high (88% among street youth; 90% among adults), and over one-third of those who
      reported engaging in NMPOU had initiated NMPOU before illegal drug use (vs.
      transitioning from illegal drugs to NMPOU). Participants who reported either
      transitioning to or from NMPOU had higher risk profiles, particularly related to
      substance use, when compared with those who reported never engaging in NMPOU. Sub
      analyses restricted to only those who engaged in NMPOU found few statistically
      significant differences between those who initiated NMPOU prior to illegal drugs
      versus those who initiated illegal drugs prior to NMPOU. Findings suggest that
      among people who use illegal drugs, early NMPOU trajectories do not appear to
      critically shape future patterns and practices.

PMID- 29338771
TI  - Regulation of aquaporins in plants under stress.
AB  - Aquaporins (AQP) are channel proteins belonging to the Major Intrinsic Protein
      (MIP) superfamily that play an important role in plant water relations. The main
      role of aquaporins in plants is transport of water and other small neutral
      molecules across cellular biological membranes. AQPs have remarkable features to
      provide an efficient and often, specific water flow and enable them to transport
      water into and out of the cells along the water potential gradient. Plant AQPs
      are classified into five main subfamilies including the plasma membrane intrinsic
      proteins (PIPs), tonoplast intrinsic proteins (TIPs), nodulin 26 like intrinsic
      proteins (NIPs), small basic intrinsic proteins (SIPs) and X intrinsic proteins
      (XIPs). AQPs are localized in the cell membranes and are found in all living
      cells. However, most of the AQPs that have been described in plants are localized
      to the tonoplast and plasma membranes. Regulation of AQP activity and gene
      expression, are also considered as a part of the adaptation mechanisms to stress
      conditions and rely on complex processes and signaling pathways as well as
      complex transcriptional, translational and posttranscriptional factors. Gating of
      AQPs through different mechanisms, such as phosphorylation, tetramerization, pH,
      cations, reactive oxygen species, phytohormones and other chemical agents, may
      play a key role in plant responses to environmental stresses by maintaining the
      uptake and movement of water in the plant body.

PMID- 29338772
TI  - Incidence, risk factors and impact of protocolised care on exposure keratopathy
      in critically ill adults: a two-phase prospective cohort study.
AB  - BACKGROUND: Exposure keratopathy (EK) has a high incidence in critically ill
      patients. We aimed to determine the rate of EK in patients admitted to our
      intensive care unit (ICU), identify risk factors for developing EK and ascertain
      the effectiveness of a protocol to prevent EK. METHODS: We undertook a two-phase
      prospective cohort single-centre study in a general adult ICU. The first phase of
      the study was observational. In the second phase of the study an eye care
      protocol was introduced. Daily ophthalmic assessment was carried out using a
      portable slit lamp. We also recorded Acute Physiology and Chronic Health
      Evaluation II score, daily Sequential Organ Failure Assessment score, mechanical
      ventilation, Richmond Agitation-Sedation Scale, and level of eye care. Student's
      t test and chi 2 statistics were used for simple analysis of continuous data and
      categorical data, respectively. Binary logistic regression was used to analyse
      the relationship between EK (yes/no), as the dependent variable, and multiple
      independent variables, calculating unadjusted and adjusted odds ratios. RESULTS:
      We studied 371 patients. In the first phase, the overall rate of EK was 21% but
      the rate in mechanically ventilated patients was 56%; chi 2 (1, N = 257) = 80.8,
      p < 0.001. Adjusted odds ratios (AOR) for development of EK were 28.6 (8.19
      43.37), 13.0 (3.16-54.38) and 1.2 (1.03-1.33) with incomplete eye closure,
      mechanical ventilation, and higher SOFA score, respectively. Following the
      introduction of the protocol in the second phase, the overall rate of EK reduced
      to 2.6% (three cases); chi 2 (1, N = 371) = 18.6, p < 0.001. Compliance with the
      protocol was 97%. CONCLUSIONS: EK is common in critically ill patients, and is
      associated with mechanical ventilation and incomplete eye closure. A simple
      protocol substantially reduces the incidence of EK and is easily achieved in
      clinical practice.

PMID- 29338773
TI  - Chemokine ligand-receptor interactions critically regulate cutaneous wound
      healing.
AB  - BACKGROUND: Wound healing represents a dynamic process involving directional
      migration of different cell types. Chemokines, a family of chemoattractive
      proteins, have been suggested to be key players in cell-to-cell communication and
      essential for directed migration of structural cells. Today, the role of the
      chemokine network in cutaneous wound healing is not fully understood. Unraveling
      the chemokine-driven communication pathways in this complex process could
      possibly lead to new therapeutic strategies in wound healing disorders. METHODS:
      We performed a systematic, comprehensive time-course analysis of the expression
      and function of a broad variety of cytokines, growth factors, adhesion molecules,
      matrixmetalloproteinases and chemokines in a murine cutaneous wound healing
      model. RESULTS: Strikingly, chemokines were found to be among the most highly
      regulated genes and their expression was found to coincide with the expression of
      their matching receptors. Accordingly, we could show that resting and activated
      human primary keratinocytes (CCR3, CCR4, CCR6, CXCR1, CXCR3), dermal fibroblasts
      (CCR3, CCR4, CCR10) and dermal microvascular endothelial cells (CCR3, CCR4, CCR6,
      CCR8, CCR9, CCR10, CXCR1, CXCR2, CXCR3) express a distinct and functionally
      active repertoire of chemokine receptors. Furthermore, chemokine ligand-receptor
      interactions markedly improved the wound repair of structural skin cells in
      vitro. CONCLUSION: Taken together, we here present the most comprehensive
      analysis of mediators critically involved in acute cutaneous wound healing. Our
      findings suggest therapeutic approaches for the management of wound closure by
      targeting the chemokine network.

PMID- 29338774
TI  - Depressive symptoms are associated with poor glycemic control among women with
      type 2 diabetes mellitus.
AB  - OBJECTIVE: In patients with type 2 diabetes mellitus, depressive symptoms may be
      associated with metabolic deterioration. The impact of sex on this association is
      unclear. The aim of this study is to analyze the relationship between depression
      and metabolic control by sex. The data presented is the side product of the
      clinical investigation by Rui Duarte, MD, Treatment Response in Type 2 Diabetes
      Patients with Major Depression from 2007. RESULTS: A sample of 628 outpatients
      with type 2 diabetes mellitus was taken from a specialized diabetes outpatient
      clinic. In a univariate analysis: women's glycohemoglobin mean levels were 8.99%
      whereas men's were 8.41% and the difference was statistically significant. The
      proportion of women (34.3%) with pathological levels of depression (Hospital
      Anxiety Depression Scale score >= 8) was significantly higher than men's (15.2%).
      A linear regression analysis performed by sex and controlling for demographic,
      clinical and psychological variables, showed poorer metabolic control in women
      with depressive symptoms. No association was observed in men. These results
      support depression as a predictor for poor metabolic control in women and the
      need for detecting depressive symptoms when glycemic levels deteriorate.

PMID- 29338775
TI  - Comparison of speckle-tracking echocardiography with invasive hemodynamics for
      the detection of characteristic cardiac dysfunction in type-1 and type-2 diabetic
      rat models.
AB  - BACKGROUND: Measurement of systolic and diastolic function in animal models is
      challenging by conventional non-invasive methods. Therefore, we aimed at
      comparing speckle-tracking echocardiography (STE)-derived parameters to the
      indices of left ventricular (LV) pressure-volume (PV) analysis to detect cardiac
      dysfunction in rat models of type-1 (T1DM) and type-2 (T2DM) diabetes mellitus.
      METHODS: Rat models of T1DM (induced by 60 mg/kg streptozotocin, n = 8) and T2DM
      (32-week-old Zucker Diabetic Fatty rats, n = 7) and corresponding control animals
      (n = 5 and n = 8, respectively) were compared. Echocardiography and LV PV
      analysis were performed. LV short-axis recordings were used for STE analysis.
      Global circumferential strain, peak strain rate values in systole (SrS),
      isovolumic relaxation (SrIVR) and early diastole (SrE) were measured. LV
      contractility, active relaxation and stiffness were measured by PV analysis.
      RESULTS: In T1DM, contractility and active relaxation were deteriorated to a
      greater extent compared to T2DM. In contrast, diastolic stiffness was impaired in
      T2DM. Correspondingly, STE described more severe systolic dysfunction in T1DM.
      Among diastolic STE parameters, SrIVR was more decreased in T1DM, however, SrE
      was more reduced in T2DM. In T1DM, SrS correlated with contractility, SrIVR with
      active relaxation, while in T2DM SrE was related to cardiac stiffness,
      cardiomyocyte diameter and fibrosis. CONCLUSIONS: Strain and strain rate
      parameters can be valuable and feasible measures to describe the dynamic changes
      in contractility, active relaxation and LV stiffness in animal models of T1DM and
      T2DM. STE corresponds to PV analysis and also correlates with markers of
      histological myocardial remodeling.

PMID- 29338776
TI  - Takayasu arteritis a cause of hypertensive disorder of pregnancy: a case report.
AB  - BACKGROUND: Takayasu arteritis is a rare, chronic, granulomatous systemic
      vasculitis of unknown etiology and a few cases have been reported in pregnancy.
      In pregnancies concomitant with Takayasu arteritis or after diagnosis, Takayasu
      arteritis negatively affects pregnancy by increasing 13-fold the odds of
      complications such as hypertensive disorders. The best recommendations in this
      scenario are still to be made. CASE PRESENTATION: We present a case of 21-year
      old, gravid 1, Mexican woman of Mestizo descent with chronic hypertension
      diagnosed since she was 15-years old who presented severe hypertension during
      pregnancy (early second trimester); the diagnosis of hypertensive disorder of
      pregnancy was ruled out requiring first-line and second-line antihypertensive
      therapy without serious associated maternal or fetal morbidity. CONCLUSIONS:
      Takayasu arteritis and pregnancy play an important role in maternal and fetal
      outcomes. Efforts should be made to further investigate the Takayasu arteritis
      diagnosis in pregnant women with refractory hypertension.

PMID- 29338777
TI  - Measuring management's perspective of data quality in Pakistan's Tuberculosis
      control programme: a test-based approach to identify data quality dimensions.
AB  - BACKGROUND: Data quality is core theme of programme's performance assessment and
      many organizations do not have any data quality improvement strategy, wherein
      data quality dimensions and data quality assessment framework are important
      constituents. As there is limited published research about the data quality
      specifics that are relevant to the context of Pakistan's Tuberculosis control
      programme, this study aims at identifying the applicable data quality dimensions
      by using the 'fitness-for-purpose' perspective. RESULTS: Forty-two respondents
      pooled a total of 473 years of professional experience, out of which 223 years
      (47%) were in TB control related programmes. Based on the responses against 11
      practical cases, adopted from the routine recording and reporting system of
      Pakistan's TB control programme (real identities of patient were masked),
      completeness, accuracy, consistency, vagueness, uniqueness and timeliness are the
      applicable data quality dimensions relevant to the programme's context, i.e. work
      settings and field of practice. CONCLUSION: Based on a 'fitness-for-purpose'
      approach to data quality, this study used a test-based approach to measure
      management's perspective and identified data quality dimensions pertinent to the
      programme and country specific requirements. Implementation of a data quality
      improvement strategy and achieving enhanced data quality would greatly help
      organizations in promoting data use for informed decision making.

PMID- 29338778
TI  - Increased whole blood FFA2/GPR43 receptor expression is associated with increased
      30-day survival in patients with sepsis.
AB  - OBJECTIVE: Sepsis is a condition associated with a dysregulated inflammatory
      response to infection with significant morbidity. Recent advances have elucidated
      the vital role that the short chain fatty acid glycoprotein receptor 43
      (FFA2/GPR43) plays in inflammatory and immunomodulatory pathways. We hypothesized
      that elevated whole blood GPR43 RNA expression would be associated with increased
      30-day survival in patients admitted with sepsis. Patients (n = 93) admitted to
      the intensive care unit with the diagnosis of sepsis underwent quantitative real
      time PCR within 48 h of intensive care unit admission. Clinical and demographical
      parameters were retrospectively extracted from the chart and compared to
      quantitative measurements of GPR43 RNA expression. RESULTS: Utilizing logistic
      regression, we found that the odds of mortality decreased for every one-unit
      increase in GPR43 RNA expression for patients that survived to 30 days [OR =
      0.71; 95% CI (0.50, 0.99) p = 0.049]. Using linear regression, we determined that
      the increase in whole blood GPR43 expression was not associated with whole blood
      white cell count [r = 0.04; 95% CI (-0.16, 0.24); p = 0.70] or body mass index [r
      = - 0.07; 95% CI (- 0.23, 0.18); p = 0.81]. We conclude that the GPR43 receptor
      plays an integral role in survival during and after sepsis.

PMID- 29338779
TI  - Comparing of two different epidemic seasons of bronchiolitis.
AB  - Acute bronchiolitis is the most common cause of hospitalizations in infants < 12
      months of age and preventive efforts remain the most important strategy to date.
      Recently prophylaxis with palivizumab (PLV) was limited to preterm infants with <
      29 weeks gestational age (wGA).We performed a single center analysis in preterm
      infants (GA between 30 and 32 weeks) and age < 12 months to compare prophylaxis
      with PLV and frequency and characteristics of bronchiolitis and bronchiolitis
      related hospitalization in two consecutive epidemic seasons (S1 vs S2).We found a
      rising trend in rate of bronchiolitis and bronchiolitis-related hospitalization
      in S1 vs S2. Among hospitalization, we found an increased morbidity with an
      increase in the rate of mechanical ventilation in S2. Additionally,
      hospitalization occurred in subjects with younger chronological age in S2
      compared with S1.Our result cannot be generalized because deriving from a single
      Center and further evaluation on wider simple size are warranted, but it suggests
      an increase in the incidence, gravity and precocity of bronchiolitis in 29-32 wGE
      preterm infants with the change in National guidelines for prophylaxis.

PMID- 29338780
TI  - Coping with dry eyes: a qualitative approach.
AB  - BACKGROUND: Dry eye is a common problem that affects many people worldwide,
      reducing quality of life and impacting daily activities. A qualitative approach
      often used in medicine and other disciplines is used to evaluate how people with
      dry eye cope with this impact. METHODS: Six focus group sessions were conducted
      at the Singapore National Eye Centre (SNEC), premises of an eye research
      institute. These focus groups consist of a spectrum of dry eye sufferers (30
      women, 8 men, aged 61 +/- 11.8 years). Standard methods of coding followed by
      determination of themes were adhered to. Where classification was difficult,
      consensus was made between 3 assessors. RESULTS: Audio-recorded transcripts were
      coded in 10 themes by 3 assessors independently. Four of the themes involved
      traditional measures such as lid warming, cleansing, lubrication and oral dietary
      supplements. The other themes discovered were Traditional Chinese Medicine,
      modification of eye-care habits (e.g. wearing sunglasses), environmental
      humidity, lifestyle (e.g. sleeping habits), psychological attitude, and lastly
      sharing and communication. CONCLUSION: Holistic coping strategies were found to
      be prominent in dry eye sufferers from these focus groups, and people tend to
      find personalised ways of coping with the impact of dry eye on daily living.

PMID- 29338781
TI  - Correlation between disease activity and serum ferritin in clinically amyopathic
      dermatomyositis with rapidly-progressive interstitial lung disease: a case
      report.
AB  - BACKGROUND: Clinically amyopathic dermatomyositis with anti-Melanoma
      Differentiation-Associated gene 5 (MDA5) antibody often presents with severe
      interstitial lung disease. Although serum ferritin level is known to reflect
      interstitial lung disease activity, there are few case reports describing this
      association. CASE PRESENTATION: A 58-year-old man was referred to our outpatient
      clinic with a 3-week history of cough and respiratory distress. He had erythema
      over the V area of the neck and a Gottron's sign. Chest computed tomography
      revealed diffuse ground-glass opacities and reticular shadows in both lungs. Test
      for anti-MDA5 antibody was positive. After admission, he received triple
      combination therapy (methylprednisolone pulse therapy, tacrolimus, and
      cyclophosphamide). However, his respiratory condition worsened as the serum
      ferritin level increased. Despite no apparent deterioration on chest radiography,
      he ultimately died due to respiratory failure. CONCLUSIONS: In this case, triple
      combination therapy was not effective for the patient's respiratory condition.
      The serum ferritin level was correlated with disease activity and was more useful
      than chest radiography for monitoring clinical status.

PMID- 29338782
TI  - Evaluation of two health education interventions to improve the varicella
      vaccination: a randomized controlled trial from a province in the east China.
AB  - BACKGROUND: We evaluated the effect of two Elaboration Likelihood Model (ELM)
      based health educational interventions on varicella vaccine (VarV) vaccination
      among pregnant women in a province in the east China. METHODS: A prospective
      randomized controlled trial was conducted among 200 pregnant women with >=12
      gestation weeks to test two interventions, including a messaging video and a
      messaging booklet. The participants were randomly assigned into the control
      group, the video group or the booklet group. The VarV coverage at 12 and 24
      months old was compared among the children of the three groups and relative risks
      (RRs) were calculated, by using the coverage of the control group as reference.
      The timeliness of VarV was also assessed. Furthermore, differences in the effects
      on the knowledge and attitude of VarV vaccination between the two interventions
      was evaluated. RESULTS: The VarV coverage of their children by 24 months of age
      was 86.4%, 76.1% and 56.7% for the video group, the booklet group and the control
      group, respectively. The relative risks (RRs) for the coverage of VarV at 24
      months of age were 4.8 (95% CI: 2.06-11.3) for the video group and 2.4 (95% CI:
      1.2-5.1) for the booklet group. The means of delays were 57.3 days in the video
      group, 76.9 days in the booklet group, and 100.6 days in the control group. The
      proportion of women who intended to vaccinate their children with VarV was higher
      in the video group than the booklet group (93.9% vs. 82.1%, p < 0.05).
      CONCLUSIONS: Our findings indicated that perinatal health education through
      booklet or video could improve the coverage and schedule adherence for children's
      VarV vaccination.

PMID- 29338783
TI  - Children with premature pubarche: is an alterated neonatal 17-Ohp screening test
      a predictive factor?
AB  - BACKGROUND: Neonatal screening for 21 hydroxylase deficiency is designed to
      detect classical form of congenital adrenal hyperplasia (CAH). It is still
      unclear whether newborns who result false positives at neonatal screening might
      later develop signs of androgen excess. The aim of this study is to verify
      whether a slightly elevated 17-OHP at newborn screening is a predictive factor
      for premature pubarche. METHODS: We evaluated all infants born between 2001 and
      2014 with premature pubarche. In case of increased bone age, they were submitted
      to functional tests to find out the cause of their symptoms. Their 17-OHP values
      at newborn screening for CAH were reconsidered. RESULTS: We identified 330
      patients (269 females, 61 males) with premature pubarche. All these children had
      a normal 17-OHP at newborn screening with the exception of a child, born preterm
      and not affected by CAH. CONCLUSIONS: An elevated 17-OHP at newborn screening is
      not a predictive factor for premature pubarche. A likely cause of increased 17
      OHP level at screening is an immaturity of adrenal gland or a neonatal stress.
      Therefore a strict follow up of these neonates during childhood is not necessary.

PMID- 29338784
TI  - Advancing STI priorities in the SDG era: priorities for action.
AB  - The Sustainable Development Goals present an opportunity to reimagine and then
      reconfigure the approach to controlling sexually transmitted infections (STIs).
      The predilection of STIs for women and for vulnerable populations means that
      services that ameliorate STIs, by their nature, enhance equity, a key focus of
      the goals. Given the considerable breadth and depth of the goals, it is important
      to locate points of convergence between the SDGs and STIs, further craft
      synergies with HIV and select a few population groups and settings to prioritise.
      There are many opportunities for STI aficionados in this era to advance the field
      and global control of these infections.

PMID- 29338785
TI  - Benefits of VCE-003.2, a cannabigerol quinone derivative, against inflammation
      driven neuronal deterioration in experimental Parkinson's disease: possible
      involvement of different binding sites at the PPARgamma receptor.
AB  - BACKGROUND: Neuroprotection with cannabinoids in Parkinson's disease (PD) has
      been afforded predominantly with antioxidant or anti-inflammatory cannabinoids.
      In the present study, we investigated the anti-inflammatory and neuroprotective
      properties of VCE-003.2, a quinone derivative of the non-psychotrophic
      phytocannabinoid cannabigerol (CBG), which may derive its activity at the
      peroxisome proliferator-activated receptor-gamma (PPARgamma). The compound is
      also an antioxidant. METHODS: We evaluated VCE-003.2 in an in vivo [mice
      subjected to unilateral intrastriatal injections of lipopolysaccharide (LPS)]
      model of PD, as well as in in vitro (LPS-exposed BV2 cells and M-213 cells
      treated with conditioned media generated from LPS-exposed BV2 cells) cellular
      models. The type of interaction of VCE-003.2 at the PPARgamma receptor was
      furtherly investigated in bone marrow-derived human mesenchymal stem cells (MSCs)
      and sustained with transcriptional assays and in silico docking studies. RESULTS:
      VCE-003.2 has no activity at the cannabinoid receptors, a fact that we confirmed
      in this study using competition studies. The administration of VCE-003.2 to LPS
      lesioned mice attenuated the loss of tyrosine hydroxylase (TH)-containing
      nigrostriatal neurons and, in particular, the intense microgliosis provoked by
      LPS in the substantia nigra, measured by Iba-1/Cd68 immunostaining. The analysis
      by qPCR of proinflammatory mediators such as tumor necrosis factor-alpha (TNF
      alpha), interleukin-1beta (IL-1beta), and inducible nitric oxide synthase (iNOS)
      in the striatum showed they were markedly elevated by the LPS lesion and strongly
      reduced by the treatment with VCE-003.2. The effects of VCE-003.2 in LPS-lesioned
      mice implied the activation of PPARgamma receptors, as they were attenuated when
      VCE-003.2 was co-administered with the PPARgamma inhibitor T0070907. We then
      moved to some in vitro approaches, first to confirm the anti-inflammatory profile
      of VCE-003.2 in cultured BV2 cells exposed to LPS. VCE-003.2 was able to
      attenuate the synthesis and release of TNF-alpha and IL-1beta, as well as the
      induction of iNOS and cyclooxygenase-2 (COX-2) elicited by LPS in these cells.
      However, we found such effects were not reversed by GW9662, another classic
      PPARgamma antagonist. Next, we investigated the neuroprotective effects of VCE
      003.2 in cultured M-213 neuronal cells exposed to conditioned media generated
      from LPS-exposed cultured BV2 cells. VCE-003.2 reduced M-213 cell death, but
      again, such effects were not reversed by T0070907. Using docking analysis, we
      detected that VCE-003.2 binds both the canonical and the alternative binding
      sites in the PPARgamma ligand-binding pocket (LBP). Functional assays further
      showed that T0070907 almost abolished PPARgamma transcriptional activity induced
      by rosiglitazone (RGZ), but it did not affect the activity of VCE-003.2 in a Gal4
      Luc system. However, T0070907 inhibited the effects of RGZ and VCE-003.2 on the
      expression of PPARgamma-dependent genes upregulated in MSCs. CONCLUSIONS: We have
      demonstrated that VCE-003.2 is neuroprotective against inflammation-driven
      neuronal damage in an in vivo model of PD and in in vitro cellular models of
      neuroinflammation. Such effects might involve PPARgamma receptors, although in
      silico and in vitro experiments strongly suggest that VCE-003.2 targets PPARgamma
      by acting through two binding sites at the LBP, one that is sensitive to T0070907
      (canonical binding site) and other that is not affected by this PPARgamma
      antagonist (alternative binding site).

PMID- 29338787
TI  - Correction to: Health effects of milder winters: a review of evidence from the
      United Kingdom.
AB  - CORRECTION: After publication of the article [1], it has been brought to our
      attention that there is an error in the abstract. The line that reads "a 1 
      degrees C fall during winter months led to reductions of 4.5%, 3.9% and 11.2%"
      should say "a 1  degrees C fall during winter months led to increases of 4.5%,
      3.9% and 11.2%".

PMID- 29338786
TI  - A systematic review of transfusion-transmitted malaria in non-endemic areas.
AB  - BACKGROUND: Transfusion-transmitted malaria (TTM) is an accidental Plasmodium
      infection caused by whole blood or a blood component transfusion from a malaria
      infected donor to a recipient. Infected blood transfusions directly release
      malaria parasites in the recipient's bloodstream triggering the development of
      high risk complications, and potentially leading to a fatal outcome especially in
      individuals with no previous exposure to malaria or in immuno-compromised
      patients. A systematic review was conducted on TTM case reports in non-endemic
      areas to describe the epidemiological characteristics of blood donors and
      recipients. METHODS: Relevant articles were retrieved from Pubmed, EMBASE,
      Scopus, and LILACS. From each selected study the following data were extracted:
      study area, gender and age of blood donor and recipient, blood component
      associated with TTM, Plasmodium species, malaria diagnostic method employed,
      blood donor screening method, incubation period between the infected transfusion
      and the onset of clinical symptoms in the recipient, time elapsed between the
      clinical symptoms and the diagnosis of malaria, infection outcome, country of
      origin of the blood donor and time of the last potential malaria exposure.
      RESULTS: Plasmodium species were detected in 100 TTM case reports with a
      different frequency: 45% Plasmodium falciparum, 30% Plasmodium malariae, 16%
      Plasmodium vivax, 4% Plasmodium ovale, 2% Plasmodium knowlesi, 1% mixed infection
      P. falciparum/P. malariae. The majority of fatal outcomes (11/45) was caused by
      P. falciparum whilst the other fatalities occurred in individuals infected by P.
      malariae (2/30) and P. ovale (1/4). However, non P. falciparum fatalities were
      not attributed directly to malaria. The incubation time for all Plasmodium
      species TTM case reports was longer than what expected in natural infections.
      This difference was statistically significant for P. malariae (p = 0.006). A
      longer incubation time in the recipient together with a chronic infection at low
      parasite density of the donor makes P. malariae a subtle but not negligible risk
      for blood safety aside from P. falciparum. CONCLUSIONS: TTM risk needs to be
      taken into account in order to enhance the safety of the blood supply chain from
      donors to recipients by means of appropriate diagnostic tools.

PMID- 29338788
TI  - High-throughput immunophenotypic characterization of bone marrow- and cord blood
      derived mesenchymal stromal cells reveals common and differentially expressed
      markers: identification of angiotensin-converting enzyme (CD143) as a marker
      differentially expressed between adult and perinatal tissue sources.
AB  - BACKGROUND: Mesenchymal stromal cells (MSC) are a heterogeneous population of
      multipotent progenitors used in the clinic because of their immunomodulatory
      properties and their ability to differentiate into multiple mesodermal lineages.
      Although bone marrow (BM) remains the most common MSC source, cord blood (CB) can
      be collected noninvasively and without major ethical concerns. Comparative
      studies comprehensively characterizing the MSC phenotype across several tissue
      sources are still lacking. This study provides a 246-antigen immunophenotypic
      analysis of BM- and CB-derived MSC aimed at identifying common and strongly
      expressed MSC markers as well as the existence of discriminating markers between
      the two sources. METHODS: BM-MSC (n = 4) were expanded and analyzed as bulk (n =
      6) or single clones isolated from the bulk culture (n = 3). CB-MSC (n = 6) were
      isolated and expanded as single clones in 5/6 samples. The BM-MSC and CB-MSC
      phenotype was investigated by flow cytometry using a panel of 246 monoclonal
      antibodies. To define the markers common to both sources, those showing the
      smallest variation between samples (coefficient of variation of log2 fold
      increase <= 0.5, n = 59) were selected for unsupervised hierarchical cluster
      analysis (HCL). Differentially expressed markers were identified by directly
      comparing the expression of all 246 antigens between BM-MSC and CB-MSC. RESULTS:
      Based on HCL, 18 markers clustered as strongly expressed in BM-MSC and CB-MSC,
      including alpha-smooth muscle antigen (SMA), beta-2-microglobulin, CD105, CD13,
      CD140b, CD147, CD151, CD276, CD29, CD44, CD47, CD59, CD73, CD81, CD90, CD98, HLA
      ABC, and vimentin. All except CD140b and alpha-SMA were suitable for the specific
      identification of ex-vivo expanded MSC. Notably, only angiotensin-converting
      enzyme (CD143) was exclusively expressed on BM-MSC. CD143 expression was tested
      on 10 additional BM-MSC and CB-MSC and on 10 umbilical cord- and adipose tissue
      derived MSC samples, confirming that its expression is restricted to adult
      sources. CONCLUSIONS: This is the first study that has comprehensively compared
      the phenotype of BM-MSC and CB-MSC. We have identified markers that could
      complement the minimal panel proposed for the in-vitro MSC definition, being
      shared and strongly expressed by BM- and CB-derived MSC. We have also identified
      CD143 as a marker exclusively expressed on MSC derived from adult tissue sources.
      Further studies will elucidate the biological role of CD143 and its potential
      association with tissue-specific MSC features.

PMID- 29338790
TI  - Morphometric characterisation of human tracheas: focus on cartilaginous ring
      variation.
AB  - PURPOSE: Details regarding tracheal anatomy are currently lacking, with existing
      literature focussing mainly on the cricoid-tracheal region or the carina.
      External gross anatomy and internal morphology throughout the entire trachea is
      important for normal physiological functioning and various clinical applications
      such as designs for tracheal implants or endotracheal devices. OBJECTIVE: To
      determine quantitative and qualitative characteristics of gross tracheal and
      individual tracheal ring anatomy. METHOD: 10 tracheas were harvested from
      formaldehyde-fixed cadavers. Tracheal length, height and inter-ring distance were
      measured from complete tracheas. Individual rings were excised and the following
      measurements were taken at three points on the ring: thickness, width, and antero
      posterior (A-P) length. RESULTS: The average tracheal length was 10.38 +/- 0.85
      cm with a mean of 19 +/- 3 rings per trachea. The average width and A-P diameter
      of tracheal lumens were 17.31 +/- 2.57 and 17.27 +/- 2.56 mm, with a width-AP
      ratio of 1.00 ('C' shaped ring). The A-P diameter shows a trend of narrowing
      slightly from the upper 1/3 to the lower 1/3 of the trachea. While majority of
      tracheal rings consisted of the expected 'C' shape, more than 41% of the 147
      counted rings consisted of abnormally shaped rings which were further analysed.
      CONCLUSION: This study provides further details regarding tracheal anatomy which
      will be useful for implant design. Of interest for anatomists, is the marked
      variability in tracheal ring morphology which could be further characterised in
      larger studies.

PMID- 29338791
TI  - Associations of the hypertension-related single nucleotide polymorphism
      rs11191548 with high-density lipoprotein cholesterol and leptin in Chinese
      children.
AB  - BACKGROUND: The genome-wide association study has founded hypertension-related
      single nucleotide polymorphism (SNP) rs11191548 near CYP17A1 encoding a key
      enzyme involved in steroid metabolism, but the molecular mechanisms are not
      understood and the associations of the SNP with hypertension-related traits are
      not fully described, especially in children. The aim of the present study is to
      investigate the associations between the SNP and two hypertension-related traits,
      lipids and leptin. METHODS: We genotyped the SNP in Beijing Child and Adolescent
      Metabolic Syndrome (BCAMS) study. A total of 3503 children participated in the
      study. RESULTS: The SNP rs11191548 was significantly associated with high-density
      lipoprotein cholesterol (HDL) (P = 0.014 and 0.028, respectively) and leptin (P =
      0.011 and 0.026, respectively) under an additive model after adjustment for age,
      gender, and systolic blood pressure (SBP) or diastolic blood pressure (DBP).
      There was a statistically significant association of rs11191548 with high leptin
      after adjustment for age, gender, and SBP or DBP. The P-values remain significant
      after correction for multiple testing. CONCLUSIONS: We demonstrate for the first
      time that the SNP rs11191548 near CYP17A1 is associated with HDL and leptin in
      Chinese children. These novel findings provide important evidence that HDL and
      leptin maybe possibly mediate the process of CYP17A1 involved in hypertension.

PMID- 29338789
TI  - Diagnosis, treatment, and response assessment in solitary plasmacytoma: updated
      recommendations from a European Expert Panel.
AB  - Solitary plasmacytoma is an infrequent form of plasma cell dyscrasia that
      presents as a single mass of monoclonal plasma cells, located either
      extramedullary or intraosseous. In some patients, a bone marrow aspiration can
      detect a low monoclonal plasma cell infiltration which indicates a high risk of
      early progression to an overt myeloma disease. Before treatment initiation, whole
      body positron emission tomography-computed tomography or magnetic resonance
      imaging should be performed to exclude the presence of additional malignant
      lesions. For decades, treatment has been based on high-dose radiation, but
      studies exploring the potential benefit of systemic therapies for high-risk
      patients are urgently needed. In this review, a panel of expert European
      hematologists updates the recommendations on the diagnosis and management of
      patients with solitary plasmacytoma.

PMID- 29338793
TI  - The institutional context of tobacco production in Zambia.
AB  - BACKGROUND: Tobacco production is said to be an important contributor to Zambia's
      economy in terms of labour and revenue generation. In light of Zambia's
      obligations under the WHO Framework Convention of Tobacco Control (FCTC) we
      examined the institutional actors in Zambia's tobacco sector to better understand
      their roles and determine the institutional context that supports tobacco
      production in Zambia. METHODS: Findings from 26 qualitative, semi-structured
      individual or small-group interviews with key informants from governmental,
      intergovernmental and non-governmental organisations were analysed, along with
      data and information from published literature. RESULTS: Although Zambia is
      obligated under the FCTC to take steps to reduce tobacco production, the
      country's weak economy and strong tobacco interests make it difficult to achieve
      this goal. Respondents uniformly acknowledged that growing the country's economy
      and ensuring employment for its citizens are the government's top priorities.
      Lacklustre coordination and collaboration between the institutional actors, both
      within and outside government, contributes to an environment that helps sustain
      tobacco production in the country. A Tobacco Products Control Bill has been under
      review for a number of years, but with no supply measures included, and with no
      indication of when or whether it will be passed. CONCLUSIONS: As with other low
      income countries involved in tobacco production, there is inconsistency between
      Zambia's economic policy to strengthen the country's economy and its FCTC
      commitment to regulate and control tobacco production. The absence of a whole-of
      government approach towards tobacco control has created an institutional context
      of duelling objectives, with some government ministries working at cross-purposes
      and tobacco interests left unchecked. With no ultimate coordinating authority,
      this industry risks being run according to the desire and demands of
      multinational tobacco companies, with few, if any, checks against them.

PMID- 29338794
TI  - A SYSTEMATIC REVIEW OF GROUP WALKING IN PHYSICALLY HEALTHY PEOPLE TO PROMOTE
      PHYSICAL ACTIVITY.
AB  - BACKGROUND: Walking is a good way to meet physical activity guidelines. We
      examined the effectiveness of walking in groups compared with walking alone or
      inactive controls in physically healthy adults on physical activity and quality
      of life. (PROSPERO CRD42016033752). METHODS: We searched Medline, Embase, Cinahl,
      Web of Knowledge Science Citation Index, and Cochrane CENTRAL until March 2016,
      for any comparative studies, in physically healthy adults, of walking in groups
      compared with inactive controls or walking alone, reporting any measure of
      physical activity. We searched references from recent relevant systematic
      reviews. Two reviewers checked study eligibility and independently extracted
      data. Disagreements were resolved through discussion. Quality was assessed using
      likelihood of selection, performance, attrition, and detection biases. Meta
      analysis was conducted using Review Manager 5.3. RESULTS: From 1,404 citations,
      18 studies were included in qualitative synthesis and 10 in meta-analyses.
      Fourteen compared group walking to inactive controls and four to walking alone.
      Eight reported more than one measure of physical activity, none reported
      according to current guidelines. Group walking compared with inactive controls
      increased follow-up physical activity (9 randomized controlled trials,
      standardized mean difference [SMD] 0.58 [95 percent confidence interval {CI},
      0.34-0.82] to SMD 0.43 [95 percent CI, 0.20-0.66]). Compared with walking alone,
      studies were too few and too heterogeneous to conduct meta-analysis, but the
      trend was improved physical activity at follow-up for group walking participants.
      Seven (all inactive control) reported quality-of-life: five showed statistically
      significantly improved scores. DISCUSSION: Better evidence may encourage
      government policy to promote walking in groups. Standardized physical activity
      outcomes need to be reported in research.

PMID- 29338792
TI  - Critical inhaler errors in asthma and COPD: a systematic review of impact on
      health outcomes.
AB  - BACKGROUND: Inhaled drug delivery is the cornerstone treatment for asthma and
      chronic obstructive pulmonary disease (COPD). However, use of inhaler devices can
      be challenging, potentially leading to critical errors in handling that can
      significantly reduce drug delivery to the lungs and effectiveness of treatment.
      METHODS: A systematic review was conducted to define 'critical' errors and their
      impact on health outcomes and resource use between 2004 and 2016, using key
      search terms for inhaler errors in asthma and COPD (Search-1) and associated
      health-economic and patient burden (Search-2). RESULTS: Search-1 identified 62
      manuscripts, 47 abstracts, and 5 conference proceedings (n = 114 total). Search-2
      identified 9 studies. We observed 299 descriptions of critical error. Age,
      education status, previous inhaler instruction, comorbidities and socioeconomic
      status were associated with worse handling error frequency. A significant
      association was found between inhaler errors and poor disease outcomes
      (exacerbations), and greater health-economic burden. CONCLUSIONS: We have shown
      wide variations in how critical errors are defined, and the evidence shows an
      important association between inhaler errors and worsened health outcomes. Given
      the negative impact diminished disease outcomes impose on resource use, our
      findings highlight the importance of achieving optimal inhaler technique, and a
      need for a consensus on defining critical and non-critical errors.

PMID- 29338795
TI  - The first report of Xenorhabdus indica from Steinernema pakistanense: co
      phylogenetic study suggests co-speciation between X. indica and its
      steinernematid nematodes.
AB  - During a survey in agricultural fields of the sub-humid region of Meerut
      district, India, two strains of entomopathogenic nematodes, labelled CS31 and
      CS32, were isolated using the Galleria baiting technique. Based on morphological
      and morphometric studies, and molecular data, the nematodes were identified as
      Steinernema pakistanense, making this finding the first report of this species
      from India. For the first time, we performed a molecular and biochemical
      characterization of the bacterial symbiont of S. pakistanense. Furthermore, a co
      phylogenetic analysis of the bacteria from the monophyletic clade containing a
      symbiont of S. pakistanense, together with their nematode hosts, was conducted,
      to test the degree of nematode-bacteria co-speciation. Both isolates were also
      tested in a laboratory assay for pathogenicity against two major pests,
      Helicoverpa armigera and Spodoptera litura. The morphology of the Indian isolates
      corresponds mainly to the original description, with the only difference being
      the absence of a mucron in first-generation females and missing epiptygmata in
      the second generation. The sequences of bacterial recA and gyrB genes have shown
      that the symbiont of S. pakistanense is closely related to Xenorhabdus indica,
      which is associated with some other nematodes from the 'bicornutum' group. Co
      phylogenetic analysis has shown a remarkable congruence between the nematode and
      bacterial phylogenies, suggesting that, in some lineages within the Steinernema /
      Xenorhabdus complex, the nematodes and bacteria have undergone co-speciation. In
      the virulence assay, both strains caused a 100% mortality of both tested insects
      after 48 h, even at the lowest doses of 25 infective juveniles per insect,
      suggesting that S. pakistanense could be considered for use in the biocontrol of
      these organisms in India.

PMID- 29338796
TI  - Cortical morphology development in patients with 22q11.2 deletion syndrome at
      ultra-high risk of psychosis.
AB  - BACKGROUND: Patients with 22q11.2 deletion syndrome (22q11DS) present a high risk
      of developing psychosis. While clinical and cognitive predictors for the
      conversion towards a full-blown psychotic disorder are well defined and largely
      used in practice, neural biomarkers do not yet exist. However, a number of
      investigations indicated an association between abnormalities in cortical
      morphology and higher symptoms severities in patients with 22q11DS. Nevertheless,
      few studies included homogeneous groups of patients differing in their psychotic
      symptoms profile. METHODS: In this study, we included 22 patients meeting the
      criteria for an ultra-high-risk (UHR) psychotic state and 22 age-, gender- and IQ
      matched non-UHR patients. Measures of cortical morphology, including cortical
      thickness, volume, surface area and gyrification, were compared between the two
      groups using mass-univariate and multivariate comparisons. Furthermore, the
      development of these measures was tested in the two groups using a mixed-model
      approach. RESULTS: Our results showed differences in cortical volume and surface
      area in UHR patients compared with non-UHR. In particular, we found a positive
      association between surface area and the rate of change of global functioning,
      suggesting that higher surface area is predictive of improved functioning with
      age. We also observed accelerated cortical thinning during adolescence in UHR
      patients with 22q11DS. CONCLUSIONS: These results, although preliminary, suggest
      that alterations in cortical volume and surface area as well as altered
      development of cortical thickness may be associated to a greater probability to
      develop psychosis in 22q11DS.

PMID- 29338797
TI  - Maternal early pregnancy obesity and depressive symptoms during and after
      pregnancy.
AB  - BACKGROUND: Previous studies have linked maternal obesity with depressive
      symptoms during and after pregnancy. It remains unknown whether obesity
      associates with consistently elevated depressive symptoms throughout pregnancy,
      predicts symptoms postpartum when accounting for antenatal symptoms, and if co
      morbid hypertensive and diabetic disorders add to these associations. We
      addressed these questions in a sample of Finnish women whom we followed during
      and after pregnancy. METHODS: Early pregnancy body mass index, derived from the
      Finnish Medical Birth Register and hospital records in 3234 PREDO study
      participants, was categorized into underweight (<18.5 kg/m2), normal weight (18.5
      24.99 kg/m2), overweight (25-29.99 kg/m2), and obese (?30 kg/m2) groups. The
      women completed the Center for Epidemiological Studies Depression Scale biweekly
      during pregnancy, and at 2.4 (s.d. = 1.2) and/or 28.2 (s.d. = 4.2) weeks after
      pregnancy. RESULTS: In comparison to normal weight women, overweight, and obese
      women reported higher levels of depressive symptoms and had higher odds of
      clinically significant depressive symptoms during (23% and 43%, respectively) and
      after pregnancy (22% and 36%, respectively). Underweight women had 68% higher
      odds of clinically significant depressive symptoms after pregnancy. Overweight
      and obesity also predicted higher depressive symptoms after pregnancy in women
      not reporting clinically relevant symptomatology during pregnancy. Hypertensive
      and diabetic disorders did not explain or add to these associations. CONCLUSIONS:
      Maternal early pregnancy overweight and obesity and depressive symptoms during
      and after pregnancy are associated. Mental health promotion should be included as
      an integral part of lifestyle interventions in early pregnancy obesity and
      extended to benefit also overweight and underweight women.

PMID- 29338798
TI  - High diversity and low genetic structure of feather mites associated with a
      phenotypically variable bird host.
AB  - Obligate symbionts may be genetically structured among host individuals and among
      phenotypically distinct host populations. Such processes may in turn determine
      within-host genetic diversity of symbionts, which is relevant for understanding
      symbiont population dynamics. We analysed the population genetic structure of two
      species of feather mites (Proctophyllodes sylviae and Trouessartia bifurcata) in
      migratory and resident blackcaps Sylvia atricapilla that winter sympatrically.
      Resident and migratory hosts may provide mites with habitats of different
      qualities, what might promote specialization of mite populations. We found high
      genetic diversity of within-host populations for both mite species, but no sign
      of genetic structure of mites between migratory and resident hosts. Our results
      suggest that, although dispersal mechanisms between hosts during the non-breeding
      season are unclear, mite populations are not limited by transmission bottlenecks
      that would reduce genetic diversity among individuals that share a host.
      Additionally, there is no evidence that host phenotypic divergence (associated
      with the evolution of migration and residency) has promoted the evolution of host
      specialist mite populations. Unrestricted dispersal among host types may allow
      symbiotic organisms to avoid inbreeding and to persist in the face of habitat
      heterogeneity in phenotypically diverse host populations.

PMID- 29338799
TI  - Going it Alone: A Scoping Review of Unbefriended Older Adults.
AB  - Older adults who have reduced decision-making capacity and no family or friends
      to compensate for these deficiencies are known as unbefriended and require a
      public guardian. The purpose of this study was to review the peer-reviewed and
      grey literature to determine the scope of available research on unbefriended
      older adults in Canada and the United States. We found limited research examining
      unbefriended older adults. No Canadian studies or reports were located.
      Unbefriended older adults were childless or had fewer children, were more
      cognitively impaired, and were older than older adults who were not unbefriended.
      These findings demonstrate a stark scarcity of studies on unbefriended older
      adults. Research is urgently needed using standardized data collection of
      guardianship status in order to enable studies of the prevalence of public
      guardianship in Canada.

PMID- 29338800
TI  - A Preliminary Investigation of Pathways to Inflated Responsibility Beliefs in
      Children with Obsessive Compulsive Disorder.
AB  - BACKGROUND: Cognitive theorists posit that inflated responsibility beliefs
      contribute to the development of obsessive compulsive disorder (OCD). Salkovskis
      et al. (1999) proposed that experiencing heightened responsibility,
      overprotective parents and rigid rules, and thinking one influenced or caused a
      negative life event act as 'pathways' to the development of inflated
      responsibility beliefs, thereby increasing risk for OCD. Studies in adults with
      OCD and non-clinical adolescents support the link between these experiences and
      responsibility beliefs (Coles et al., 2015; Halvaiepour and Nosratabadi, 2015),
      but the theory has never been tested in youth with current OCD. AIMS: We provided
      an initial test of the theory by Salkovskis et al. (1999) in youth with OCD. We
      predicted that childhood experiences proposed by Salkovskis et al. (1999) would
      correlate positively with responsibility and harm beliefs and OCD symptom
      severity. METHOD: Twenty youth with OCD (age 9-16 years) completed a new child
      report measure of the experiences hypothesized by Salkovskis et al. (1999), the
      Pathways to Inflated Responsibility Beliefs Scale-Child Version (PIRBS-CV). Youth
      also completed the Obsessive Beliefs Questionnaire-Child Version (Coles et al.,
      2010) and the Obsessive Compulsive Inventory-Child Version (Foa et al., 2010).
      RESULTS: Consistent with hypotheses, the PIRBS-CV was significantly related to
      responsibility and harm beliefs and OCD symptom severity. CONCLUSIONS: Results
      provide initial support for the theory proposed by Salkovskis et al. (1999) as
      applied to youth with OCD. Future studies are needed to further assess the model
      in early-onset OCD.

PMID- 29338801
TI  - How immediate and significant is the outcome of training on diversified diets,
      hygiene and food safety? An effort to mitigate child undernutrition in rural
      Malawi.
AB  - OBJECTIVE: The present study examined the impacts of training on nutrition,
      hygiene and food safety designed by the Nutrition Working Group, Child Survival
      Collaborations and Resources Group (CORE). DESIGN: Adapted from the 21d Positive
      Deviance/Hearth model, mothers were trained on the subjects of appropriate
      complementary feeding, water, sanitation and hygiene (WASH) practices, and
      aflatoxin contamination in food. To assess the impacts on child undernutrition, a
      randomised controlled trial was implemented on a sample of 179 mothers and their
      children (<2 years old) in two districts of Malawi, namely Mzimba and Balaka.
      Settings A 21d intensive learning-by-doing process using the positive deviance
      approach. SUBJECTS: Malawian children and mothers. RESULTS: Difference-in
      difference panel regression analysis revealed that the impacts of the
      comprehensive training were positive and statistically significant on the Z
      scores for wasting and underweight, where the effects increased constantly over
      time within the 21d time frame. As for stunting, the coefficients were not
      statistically significant during the 21d programme, although the level of
      significance started increasing in 2 weeks, indicating that stunting should also
      be alleviated in a slightly longer time horizon. CONCLUSIONS: The study clearly
      suggests that comprehensive training immediately guides mothers into improved
      dietary and hygiene practices, and that improved practices take immediate and
      progressive effects in ameliorating children's undernutrition.

PMID- 29338802
TI  - Separating Common from Unique Variance Within Emotional Distress: An Examination
      of Reliability and Relations to Worry.
AB  - BACKGROUND: High comorbidity rates among emotional disorders have led researchers
      to examine transdiagnostic factors that may contribute to shared psychopathology.
      Bifactor models provide a unique method for examining transdiagnostic variables
      by modelling the common and unique factors within measures. Previous findings
      suggest that the bifactor model of the Depression Anxiety and Stress Scale (DASS)
      may provide a method for examining transdiagnostic factors within emotional
      disorders. AIMS: This study aimed to replicate the bifactor model of the DASS, a
      multidimensional measure of psychological distress, within a US adult sample and
      provide initial estimates of the reliability of the general and domain-specific
      factors. Furthermore, this study hypothesized that Worry, a theorized
      transdiagnostic variable, would show stronger relations to general emotional
      distress than domain-specific subscales. METHOD: Confirmatory factor analysis was
      used to evaluate the bifactor model structure of the DASS in 456 US adult
      participants (279 females and 177 males, mean age 35.9 years) recruited online.
      RESULTS: The DASS bifactor model fitted well (CFI = 0.98; RMSEA = 0.05). The
      General Emotional Distress factor accounted for most of the reliable variance in
      item scores. Domain-specific subscales accounted for modest portions of reliable
      variance in items after accounting for the general scale. Finally, structural
      equation modelling indicated that Worry was strongly predicted by the General
      Emotional Distress factor. CONCLUSIONS: The DASS bifactor model is generalizable
      to a US community sample and General Emotional Distress, but not domain-specific
      factors, strongly predict the transdiagnostic variable Worry.

PMID- 29338803
TI  - Socio-demographic inequalities in the clinical characteristics of dengue
      haemorrhagic fever in the city of Rio de Janeiro, Brazil, 2007-2008.
AB  - In 2007-2008, the city of Rio de Janeiro underwent an epidemiological change,
      with increases in the incidence in children and in severe forms of dengue. To
      describe the clinical profile and spatial distribution of dengue we performed an
      ecological study based on dengue surveillance data using the Brazilian
      classification (2005): dengue fever, dengue haemorrhagic fever (DHF) and dengue
      with complications. chi 2 test was used to describe the clinical and socio
      demographic variables (P < 0.05). Spatial distribution of incidence and case
      fatality was explored with thematic maps, Moran and Geary indices (P < 0.05). Of
      the total of 151 527 dengue cases, 38 808 met the inclusion criteria; 42.4% <18
      years; 22.9% dengue with complications and 2.7% DHF. Case-fatality was higher in
      infants (1.4%) and in DHF (7.7%). Bleeding was more frequent in adolescents and
      adults while plasma leakage was more common in preschoolers and schoolchildren.
      The highest incidence was found in the West Zone of the city, in a different area
      from that of the worst case-fatality (P < 0.05). Although the incidence of DHF
      was higher in schoolchildren, infants showed higher case-fatality. The area with
      the highest case-fatality did not present the highest incidence, which suggests
      problems in the organization of health services.

PMID- 29338804
TI  - Public health response to a measles outbreak on a university campus in Australia,
      2015.
AB  - This report describes the effective public health response to a measles outbreak
      involving a university campus in Brisbane, Australia. Eleven cases in total were
      notified, mostly university students. The public health response included
      targeted measles vaccination clinics which were established on campus and focused
      on student groups most likely to have been exposed. The size of the university
      population, social interaction between students on and off campus, as well as
      limited vaccination records for the university community presented challenges for
      the control of this extremely infectious illness. We recommend domestic students
      ensure vaccinations are current prior to matriculation. Immunisation information
      should be included in university student enrolment packs. Incoming international
      students should ensure routine vaccinations are up-to-date prior to arrival in
      Australia, thereby reducing the risk of importation of measles and other
      infectious diseases.

PMID- 29338805
TI  - Risk factors for infectiousness of patients with tuberculosis: a systematic
      review and meta-analysis.
AB  - We performed a systematic review and meta-analyses of studies assessing
      tuberculosis (TB) patient-related risk factors for transmission of Mycobacterium
      tuberculosis infection. Meta-analyses were conducted for sputum smear-positivity,
      lung cavitation and HIV seropositivity of index patients with both crude and
      adjusted odds ratios (AORs) pooled using random effect models. Thirty-seven
      studies were included in the review. We found that demographic characteristics
      such as age and sex were not significant risk factors, while behaviours such as
      smoking and alcohol intake were associated with infectiousness although
      inconsistently. Treatment delay of >28 days was a significant predictor of
      greater infectiousness. Contacts of sputum smear-positive index patients were
      found to be more likely to be infected than contacts of sputum smear-negative
      patients, with a pooled AOR of 2.15 (95% confidence interval (CI) 1.47-3.17, I 2
      = 38%). Similarly, contacts of patients with the cavitary disease were around
      twice as likely to be infected as contacts of patients without cavitation (pooled
      AOR 1.9, 95% CI 1.26-2.84, I 2 = 63%). In contrast, HIV seropositive patients
      were associated with few contact infections than HIV seronegative patients (AOR
      0.45, 95% CI 0.26-0.80, I 2 = 52%). In conclusion, behavioural and clinical
      characteristics of TB patients can be used to identify highly infectious patients
      for targeted interventions.

PMID- 29338806
TI  - Cancer pain management needs and perspectives of patients from Chinese
      backgrounds: a systematic review of the Chinese and English literature.
AB  - OBJECTIVE: More than half of all cancer patients experience unrelieved pain.
      Culture can significantly affect patients' cancer pain-related beliefs and
      behaviors. Little is known about cultural impact on Chinese cancer patients' pain
      management. The objective of this review was to describe pain management
      experiences of cancer patients from Chinese backgrounds and to identify barriers
      affecting their pain management. METHOD: A systematic review was conducted
      adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses
      guidelines. Studies were included if they reported pain management experiences of
      adult cancer patients from Chinese backgrounds. Five databases were searched for
      peer-reviewed articles published in English or Chinese journals between1990 and
      2015. The quality of included studies was assessed using Joanna Briggs
      Institution's appraisal tools. RESULTS: Of 3,904 identified records, 23 articles
      met criteria and provided primary data from 6,110 patients. Suboptimal analgesic
      use, delays in receiving treatment, reluctance to report pain, and/or poor
      adherence to prescribed analgesics contributed to the patients' inadequate pain
      control. Patient-related barriers included fatalism, desire to be good, low pain
      control belief, pain endurance beliefs, and negative effect beliefs. Patients and
      family shared barriers about fear of addiction and concerns on analgesic side
      effects and disease progression. Health professional-related barriers were poor
      communication, ineffective management of pain, and analgesic side effects.
      Healthcare system-related barriers included limited access to analgesics and/or
      after hour pain services and lack of health insurance. Significance of results
      Chinese cancer patients' misconceptions regarding pain and analgesics may present
      as the main barriers to optimal pain relief. Findings of this review may inform
      health interventions to improve cancer pain management outcomes for patients from
      Chinese backgrounds. Future studies on patients' nonpharmacology intervention
      related experiences are required to inform multidisciplinary and biopsychosocial
      approaches for culturally appropriate pain management.

PMID- 29338807
TI  - Genetic diversity of Blastocystis in non-primate animals.
AB  - Blastocystis is an anaerobic protist, commonly inhabiting the intestinal tract of
      both humans and other animals. Blastocystis is extremely diverse comprising 17
      genetically distinct subtypes in mammals and birds. Pathogenicity of this enteric
      microbe is currently disputed and knowledge regarding its distribution, diversity
      and zoonotic potential is fragmentary. Most research has focused on Blastocystis
      from primates, while sampling from other animals remains limited. Herein, we
      investigated the prevalence and distribution of Blastocystis in animals held
      within a conservation park in South East England. A total of 118 samples were
      collected from 27 vertebrate species. The barcoding region of the small-subunit
      ribosomal RNA was used for molecular identification and subtyping. Forty one per
      cent of the species were sequence positive for Blastocystis indicating a high
      prevalence and wide distribution among the animals in the park. Six subtypes were
      identified, one of which is potentially novel. Moreover, the majority of animals
      were asymptomatic carriers, suggesting that Blastocystis is not pathogenic in
      animals. This study provides a thorough investigation of Blastocystis prevalence
      within a wildlife park in the UK and can be used as a platform for further
      investigations on the distribution of other eukaryotic gut microbes.

PMID- 29338808
TI  - Ceratomyxa gracillima n. sp. (Cnidaria: Myxosporea) provides evidence of panmixia
      and ceratomyxid radiation in the Amazon basin.
AB  - We describe a new freshwater myxosporean species Ceratomyxa gracillima n. sp.
      from the gall bladder of the Amazonian catfish Brachyplatystoma rousseauxii; the
      first myxozoan recorded in this host. The new Ceratomyxa was described on the
      basis of its host, myxospore morphometry, ssrDNA and internal transcribed spacer
      region (ITS-1) sequences. Infected fish were sampled from geographically distant
      localities: the Tapajos River, Para State, the Amazon River, Amapa State and the
      Solimoes River, Amazonas State. Immature and mature plasmodia were slender,
      tapered at both ends, and exhibited vermiform motility. The ribosomal sequences
      from parasite isolates from the three localities were identical, and distinct
      from all other Ceratomyxa sequences. No population-level genetic variation was
      observed, even in the typically more variable ITS-1 region. This absence of
      genetic variation in widely separated parasite samples suggests high gene flow as
      a result of panmixia in the parasite populations. Maximum likelihood and maximum
      parsimony analyses placed C. gracillima n. sp. sister to Ceratomyxa vermiformis
      in a subclade together with Ceratomyxa brasiliensis and Ceratomyxa amazonensis,
      all of which have Amazonian hosts. This subclade, together with other Ceratomyxa
      from freshwater hosts, formed an apparently early diverging lineage. The
      Amazonian freshwater Ceratomyxa species may represent a radiation that originated
      during marine incursions into the Amazon basin that introduced an ancestral
      lineage in the late Oligocene or early Miocene.

PMID- 29338810
TI  - Detection of mcr-4 positive Salmonella enterica serovar Typhimurium in clinical
      isolates of human origin, Italy, October to November 2016.
AB  - In this study we report the detection of the recently described mcr-4 gene in two
      human isolates of Salmonella enterica serovar Typhimurium. The strains were
      isolated from faecal samples of two Italian patients with gastroenteritis,
      collected in 2016. The identified mcr-4 genes (variant mcr-4.2) differed from the
      mcr-4 gene originally described in a Salmonella strain of swine origin from
      Italy. Salmonella species could represent a hidden reservoir for mcr genes.

PMID- 29338811
TI  - Ongoing nationwide outbreak of Salmonella Agona associated with internationally
      distributed infant milk products, France, December 2017.
AB  - On 1 December 2017, an outbreak of Salmonella Agona infections among infants was
      identified in France. To date, 37 cases (median age: 4 months) and two further
      international cases have been confirmed. Five different infant milk products
      manufactured at one facility were implicated. On 2 and 10 December, the company
      recalled the implicated products; on 22 December, all products processed at the
      facility since February 2017. Trace-forward investigations indicated product
      distribution to 66 countries.

PMID- 29338809
TI  - Comparison of influenza vaccine effectiveness in preventing outpatient and
      inpatient influenza cases in older adults, northern Spain, 2010/11 to 2015/16.
AB  - IntroductionWe compared trivalent inactivated influenza vaccine effectiveness
      (VE) in preventing outpatient and inpatient influenza cases in Navarre, Spain.
      Methods: During seasons 2010/11 to 2015/16, community-dwelling patients with
      influenza-like illness aged 50 years or older were tested for influenza when
      attended by sentinel general practitioners or admitted to hospitals. The test
      negative design was used to estimate and compare the VE by healthcare setting.
      Results: We compared 1,242 laboratory-confirmed influenza cases (557 outpatient
      and 685 inpatient cases) and 1,641 test-negative controls. Influenza VE was 34%
      (95% confidence interval (CI): 6 to 54) in outpatients and 32% (95% CI: 15 to 45)
      in inpatients. VE in outpatients and inpatients was, respectively, 41% (95% CI: 
      1 to 65) and 36% (95% CI: 12 to 53) against A(H1N1)pdm09, 5% (95% CI: -58 to 43)
      and 22% (95% CI: -9 to 44) against A(H3N2), and 49% (95% CI, 6 to 73) and 37%
      (95% CI: 2 to 59) against influenza B. Trivalent inactivated influenza vaccine
      was not associated with a different probability of hospitalisation among
      influenza cases, apart from a 54% (95% CI: 10 to 76) reduction in hospitalisation
      of influenza A(H3N2) cases. Conclusions: On average, influenza VE was moderate
      and similar in preventing outpatient and inpatient influenza cases over six
      influenza seasons in patients above 50 years of age. In some instances of low VE,
      vaccination may still reduce the risk of hospitalisation in older adults with
      vaccine failure.

PMID- 29338812
TI  - Comprehensive assessment of the quality of Salmonella whole genome sequence data
      available in public sequence databases using the Salmonella in silico Typing
      Resource (SISTR).
AB  - Public health and food safety institutions around the world are adopting whole
      genome sequencing (WGS) to replace conventional methods for characterizing
      Salmonella for use in surveillance and outbreak response. Falling costs and
      increased throughput of WGS have resulted in an explosion of data, but questions
      remain as to the reliability and robustness of the data. Due to the critical
      importance of serovar information to public health, it is essential to have
      reliable serovar assignments available for all of the Salmonella records. The
      current study used a systematic assessment and curation of all Salmonella in the
      sequence read archive (SRA) to assess the state of the data and their utility. A
      total of 67 758 genomes were assembled de novo and quality-assessed for their
      assembly metrics as well as species and serovar assignments. A total of 42 400
      genomes passed all of the quality criteria but 30.16 % of genomes were deposited
      without serotype information. These data were used to compare the concordance of
      reported and predicted serovars for two in silico prediction tools, multi-locus
      sequence typing (MLST) and the Salmonella in silico Typing Resource (SISTR),
      which produced predictions that were fully concordant with 87.51 and 91.91 % of
      the tested isolates, respectively. Concordance of in silico predictions increased
      when serovar variants were grouped together, 89.25 % for MLST and 94.98 % for
      SISTR. This study represents the first large-scale validation of serovar
      information in public genomes and provides a large validated set of genomes,
      which can be used to benchmark new bioinformatics tools.

PMID- 29338813
TI  - Note from the editors: As time goes by.

PMID- 29338814
TI  - The Use of Visual Examination for Determining the Presence of Gluten-Containing
      Grains in Gluten Free Oats and Other Grains, Seeds, Beans, Pulses, and Legumes.
AB  - Obtaining representative test samples for antibody-based testing is challenging
      when analyzing whole grains for gluten. When whole grains are ground into flour
      for testing, confocal microscopy studies have shown that gluten tends to exist as
      aggregates within the starch background, making single-sample testing inaccurate
      and complicating the ability to arrive at an accurate average from multiple
      samples. In addition, whole-grain products present a unique risk to gluten free
      consumers, in that any contamination is localized to specific servings rather
      than being distributed across the product lot. This makes parts-per-million
      values less relevant for whole-grain products. Intact grains, seeds, beans,
      pulses, and legumes offer an alternative opportunity for gluten detection, in
      that contaminating gluten-containing grains (GCGs) are visible and identifiable
      to the trained eye or properly calibrated optical sorting equipment. The purpose
      of the current study was to determine a Gluten Free Certification Organization
      threshold level for the maximum number of GCGs within a kilogram of nongluten
      grains sold as specially processed gluten free product and to determine the
      feasibility of this threshold by evaluating visual examination data from two
      major oat processors.

PMID- 29338815
TI  - Correlation between the Expression of High Temperature Requirement Serine
      Protease A1 in Nucleus Pulposus Tissue and the Degree of Intervertebral Disc
      Degeneration.
AB  - Objective To investigate the correlation between the expression level of high
      temperature requirement serine protease A1 (HtrA1) in nucleus pulposus and the
      degree of intervertebral disc degeneration (Pfirrmann grade).Methods Thirty-six
      patients who underwent excision of nucleus pulposus were examined by magnetic
      resonance imaging (MRI) before operation,and the Pfirrmann grading of all
      patients was performed according to the sagittal T2 weighted MRI.The expression
      of HtrA1 in nucleus pulposus tissue was detected by reverse transcription
      polymerase chain reaction and Western blot.The correlation between the expression
      level of HtrA1 in nucleus pulposus tissue and Pfirrmann grade was
      analyzed.Results MRI in all 36 patients showed that there were 3 cases of
      Pfirrmann grade I,10 cases of grade II,11 cases of grade III,7 cases of grade
      III,and 5 cases of grade V.The mRNA and protein expressions of HtrA1 in nucleus
      pulposus tissue increased with the increase of Pfirrmann grade.There were
      significant differences in the expression level of HtrA1 among different
      Pfirrmann grade groups (P<0.05) except for the difference between grade III and V
      (P>0.05).Spearman rank correlation analysis revealed that there was a rank
      correlation between expression level of HtrA1 and Pfirrmann grade (P<0.000
      1).Conclusion The mRNA and protein expressions of HtrA1 in nucleus pulposus
      tissue increase with the increase of Pfirrmann grade,indicating HtrA1 is
      correlated with the degree of intervertebral disc degeneration.

PMID- 29338816
TI  - Fabrication of Isoniazid/Rifampicin/Poly L-lactic Acid Donut-shaped Implants via
      Three Dimensional Printing Technique.
AB  - Objective To investigate the possibility of manufacturing dual-drug loaded
      isoniazid/rifampicin/poly L-lactic acid (PLLA) implant with donut-shaped
      structure via three-dimensional (3D) printing technique and study the drug
      release characteristic and biocompatibility of the implant in vitro.Methods PLLA
      was crushed into particles with diameters around 75-100 MUm.Isoniazid and
      rifampicin bulk drugs were dissolved into the organic dissolvent respectively to
      be the binding liquid.The 3D printing machine fabricated the donut-shaped implant
      via binding the PLLA powder layer by layer.Dynamic socking method was used to
      study the in vitro release characteristics,and cell culture experiment was used
      to test the cytocompatibility of the implant.Results PLLA slow-release implants
      were made by using the PLLA powder as matrix and isoniazid/rifampicin organic
      solvent as binding liquid through 3D printing.The drugs in the implants
      distributed in nest under electron microscope.The concentrations of both drugs
      were still higher than the lowest effective bacteriostasis concentration after
      release for 32 days.Cytotoxicity and direct contact tests indicated that the
      implants had rare cytotoxicity and favorable biocompatibility. Conclusion The
      donut-shaped implants can be successfully fabricated using the 3D printing
      method,which offers a new method for the manufacturing of topical slow-release
      anti-tuberculosis drugs.

PMID- 29338817
TI  - Correlation of Stress Hyperglycemia after Ischemic Stroke with Early Vascular
      Cognitive Impairment.
AB  - Objective To investigate the influence and forecast value of stress hyperglycemia
      on the early vascular cognitive impairment (VCI) in stroke patients.Methods
      Totally 422 patients with acute non-diabetic stroke were divided into three
      groups according to the fasting plasma glucose level:the euglycemia group (<6.1
      mmol/L),the mild stress hyperglycemia group (6.1-7.0 mmol/L),and the severe
      stress hyperglycemia group (>=7.0 mmol/L).Mini-mental state
      examination,Alzheimer's disease rating scale cognitive subscale,and clinical
      dementia rating scale were used to evaluate early cognition in post-stroke
      patients,and patients were divided into three groups accordingly:normal cognitive
      function group,mild VCI group,and vascular dementia group.Correlation analysis
      was carried out on the level of stress hyperglycemia and the degree of
      VCI.Results Of these 422 patients,stress hyperglycemia was identified in 62 cases
      (14.7%).The risk of stress hyperglycemia was higher in patients with a high
      degree of education [(8.39+/-3.85)years vs.(6.62+/-4.39)years,P=0.037)] or a
      history of cardiovascular disease (45.2% vs.18.3%,P=0.001).VCI was detected in
      270 patients (64.0%).Age,sex,smoking,National Institute of Health Stroke Scale
      score,Hamilton Depression Rating Scale score,stress hyperglycemia,and history of
      cardiovascular disease were related with early VCI after non-diabetic ischemic
      stroke (P<0.05).Multivariate Logistic regression analysis showed that stress
      hyperglycemia was an independent risk factor for VCI in patients with non
      diabetic ischemic stroke (OR=3.086,95% CI=1.065-8.929).The risks of cognitive
      impairment in the mild stress hyperglycemia group and the severe stress
      hyperglycemia group were higher than that of the euglycemia group,while it was
      also higher in the severe stress hyperglycemia group than in the mild stress
      hyperglycemia group (61.11% vs.75.00% vs.90.91%).Stress hyperglycemia was
      positively correlated with the high risk of early cognitive impairment in stroke
      patients (rs=0.185,P=0.007).Conclusion There is a significant correlation between
      stress hyperglycemia and early VCI after ischemic stroke.

PMID- 29338818
TI  - Expression and Function of Long Non-coding RNA CASC19 in Colorectal Cancer.
AB  - Objective To investigate the expression, function and significance of long non
      coding RNA (lncRNA) CASC19 in colorectal cancer (CRC). Methods Real-time
      quantitative polymerase chain reaction was employed to determine the expression
      of CASC19 in 40 paired samples from CRC surgical specimens and 5 CRC cell lines.
      The correlations of CASC19 expression with clinicopathologic parameters were
      analyzed. Transwell assay was applied to detect the migration ability of CRC
      cells after the CASC19 expression was knocked down by small interfering RNA.
      Results The expression of CASC19 in colorectal cancer was significantly higher
      than those in adjacent normal mucosa tissues (t=5.527, P<0.000 1) and was
      associated with metastasis (P=0.044). Knockdown of CASC19 expression in CRC
      inhibited the migration ability of CRC in vitro. Conclusions The expression of
      CASC19 increases in CRC. CASC19 expression is not associated with age, gender, or
      tumor site/differentiation but with tumor size, lymph node metastasis, and
      distant metastasis, suggesting high CASC19 expression may promote CRC metastasis.

PMID- 29338819
TI  - In Vitro Efficacy of Continuous Mild High Temperature on the Biofilm Formation of
      Aspergillus Niger.
AB  - Objective To investigate whether continuous mild high temperature (increased
      temperature without causing significant damage to host cells) can inhibit the
      biofilm formation of Aspergillus niger (A.niger) and its vitality.Methods A.niger
      biofilms were formed on a coverslip in 24-well tissue culture plate and were
      checked at the time points 4,8,10,16,24,48 and 72 hours.Confocal laser scanning
      microscopy (CLSM) was used to image and quantify A.niger biofilm formation under
      three different continuous mild high temperatures at 37C,39C,and
      41C.Furthermore,2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5
      carboxanilide (XTT) assay was used to quantify the dynamic growth of A.niger
      biofilm under the above conditions.Results Compared with the culture condition
      37C,CLSM analysis at 39C or 41C showed that higher temperature induced later
      germination at 4 hours (t=8.603,P=0.047;t=14.550,P=0.008),poorer hyphal
      elongation at 8 hours(t=35.118,P=0.039;t=63.450,P=0.006),poorer polar growth,and
      reduced biofilm thickness from 10 to 24 hours.The XTT assay showed that higher
      temperature (39C or 41C) lead to lower vitality at 10 hours,higher vitality at 16
      hours,but finally lower vitality from 24 to 72 hours
      (t=24.262,P=0.038;t=7.556,P=0.031).Conclusion Continuous mild high temperature
      may have a negative regulatory effect on biofilm formation of A.niger and its
      vitality.

PMID- 29338820
TI  - Preoperative Evaluation of the Grade and Stability of Osteochondritis Dissecans
      of the Knee by Magnetic Resonance Imaging.
AB  - Objective To assess the diagnostic performance of magnetic resonance imaging
      (MRI) in the grading of osteochondritis dissecans (OCD) of the knee.Methods
      Totally 47 patients with OCD of the knee confirmed by arthroscopy were
      retrospectively enrolled in this study.The OCD lesions were classified into four
      stages according to classification system of the International Cartilage Repair
      Society.Two radiologists analyzed all MRI findings independently,and the results
      were compared with those of arthroscopy.Sensitivity,specificity,and accuracy were
      calculated.Kappa value were calculated to quantify inter-observer agreement of
      the diagnostic OCD grade between two doctors by MRI.Specificity,sensitivity,and
      accuracy of MRI criteria indicating instability for detection of OCD instability
      were calculated.Results Of these 47 patients with 48 OCD lesions,stages
      I,II,III,and III lesions were detected in 4,8,16,and 20 patients,respectively.The
      specificity,sensitivity,and accuracy for the diagnosis of OCD stability were
      75.0% (83.3%),88.9% (86.1%),and 85.4% (85.4%) for observer l (2),and the
      agreement of OCD grade between these two readers was substantial with a Kappa
      value of 0.82.The specificity,sensitivity,and accuracy of MRI criteria for the
      detection of OCD instability including high T2 signal intensity at the interface
      between the OCD and the underlying bone,multiple cysts or a single cyst of>5 mm
      in diameter surrounding OCD lesions,high T2 signal intensity cartilage fracture
      line traversing the articular cartilage,and osteochondral defect were
      83.3%,80.6%,and 81.3%;75.0%,72.2%,and 72.9%;66.7%,69.4%,and 68.8%;100%,86.1%,and
      89.6%,respectively. Conclusions Osteochondral defect is the most specific MRI
      sign for diagnosing instable OCD of the knee,whereas osteochondral fracture line
      has the lowest accuracy.MRI is a useful method to evaluate the grade and
      stability of OCD of the knee.

PMID- 29338821
TI  - Factors Influencing Regional Cerebral Oxygen Saturation during One-lung
      Ventilation in Thoracic Surgery.
AB  - Objective To identify factors influencing regional cerebral oxygen saturation
      (rScO2) during one-lung ventilation (OLV) in thoracic surgery. Methods Totally 33
      patients with an ASA physical status of 1-3 scheduled for elective thoracic
      surgery with one-lung ventilation under general anesthesia were recruited. After
      anesthesia was induced with propofol,fentanyl/sufentanil,and rocuronium. All
      patients received balanced anesthesia using sevoflurane. During OLV,volume
      controlled ventilation was used with a tidal volume of 6-7 ml/kg and an
      inspiration:expiration ratio of 1:1.5. The ventilator frequency was adjusted with
      a target end-tidal carbon dioxide partial pressure (PetCO2) between 35 mmHg and
      45 mmHg. During the anesthesia,patients were maintained at a pulse oxygen
      saturation (SpO2) of>90%,systolic blood pressure (SBP) of>90 mmHg (or reducing no
      more than 30% of the basic values),heart rate (HR) of>50 beat/min,and hemoglobin
      concentration of>90 g/L. Changes of rScO2 were monitored with FORESIGHT probes by
      specialized researchers. Patients were classified into low rScO2 (L-rScO2) group
      (n=10) or high rScO2 (H-rScO2)group(n=23) according to whether the lowest
      intraoperative rScO2 was under 65% or 15% lower than the baseline values. We
      compared gender,age,body mass index (BMI),intraoperative hemoglobin level,and the
      values of peak airway pressure (Ppeak),SBP,PetCO2,and SpO2 when rScO2 dropped to
      the lowest level between these two groups. Results Statistically higher Ppeak and
      lower SBP were noted in the L-rScO2 group compared with H-rScO2 group
      (P=0.028,P=0.046). SpO2 was lower in the L-rScO2 group compared with H-rScO2
      group,but the difference was not statistically significant (P=0.421). There was
      also no significant difference between the two groups according to
      age,BMI,SpO2,PetCO2,or hemoglobin level. Ppeak appeared to be a risk factor for
      rScO2 reduction during OLV,as shown by unconditioned Logistic regression
      analysis. Conclusion During OLV in thoracic surgery,Ppeak is a risk factor for
      rScO2 reduction.

PMID- 29338822
TI  - Assessment of Early Clopidogrel Therapy Use among Acute Myocardial Infarction
      Patients in Central-rural China in 2006 and 2011.
AB  - Objective To explore the application and influencing factors of early clopidogrel
      use in patients with acute myocardial infarction (AMI) in the central-rural
      region of China in 2006 and 2011. Methods A representative sample of patients in
      central-rural region of China admitted to hospital for AMI was created from a two
      stage random sampling. In the first phase,a simple random-sampling procedure was
      used to identify participating hospitals. In the second stage,we selected
      patients admitted to each participating hospitals for AMI with a systematic
      sampling approach. Then we obtained clinical information via central medical
      record abstraction for each patient. For analysis of early clopidogrel therapy
      (within 24 hours of admission) status,we used multilevel Logistical regression
      models with the use of generalized estimating equations. Results We identified
      1464 patients eligible for early clopidogrel therapy. From 2006 to 2011,the early
      application rate of clopidogrel increased significantly,from 3.98% to 48.72%
      (P<0.0001). Logistic regression analysis showed that patients with hypertension
      were more likely to receive early clopidogrel(OR=1.65,95% CI=1.21
      2.26,P=0.001),smokers were associated with greater likelihood to receive early
      clopidogrel(OR=1.87,95% CI=1.19-2.95,P=0.007),and patients with chest discomfort
      during hospitalization indicated association with higher likelihood of early
      clopidogrel use within 24 hours of admission (OR=2.17,95% CI=1.35-3.49,P=0.001).
      Conclusions Early clopidogrel use in AMI patients has been improved from 2006 to
      2011. However,tremendous gap still exists between guidelines and clinical
      practice. Quality improvement initiatives are in urgent need to support further
      improvements in early clopidogrel use for AMI patients.

PMID- 29338823
TI  - Relationship of Methylation within Upper Stream Region of Transcription Starts
      Site of HOXA5 Gene with Neural Tube Defects.
AB  - Objective To investigate the relationship between the methylation level of
      transcription starts site (TSS) upper stream of homeobox gene and the neural tube
      defects (NTDs). Methods A case-control study of two stages was designed. In the
      first stage,10 cases and 8 controls were extracted,in whom Illumina Infinium
      Human Methylation 450 k genome-wide beadchip was used for the quantification of
      DNA methylation levels of brain and spinal tissue. In the second
      stage,differentially methylated region within HOXA5 gene was detected with a
      larger numbers of samples (52 cases and 23 controls). DNA of brain or spinal
      tissue was extracted,and Matrix-assisted laser desorption ionization time-of
      flight mass spectrometry technique of MassARRAY platform was employed for the
      validation of differentially methylated region of HOXA5 gene. Results In the
      first stage,27 CpG sites within TSS region of HOXA5 gene were found to be
      significantly hyper-methylated in case group compared to control group (P<0.05).
      In the second stage,a total of 10 CpG sites were analyzable within the
      differentially methylated region in the first stage. In the NTD case group,spinal
      bifida subgroup,and anencephaly subgroup,there were 7,6,and 2 sites with
      significantly higher methylation levels than that of control group (P<0.05). The
      average methylation level of TSS upper stream region within HOXA5 gene was higher
      in case group than control group [case group:(31.3+/-13.9)%,control group:(21.4+/
      9.7)%],and the odds ratio after adjusting gender of fetus and pregnant week was
      1.09 (1.03-1.16). Conclusion Hypermethylation within TSS upper stream region of
      HOXA5 gene in fetus is associated with a higher risk of NTDs.

PMID- 29338824
TI  - Effects of Preoperative Isokinetic Eccentric Training and Whey Protein Isolate
      Supplement on Quadriceps Strength and Knee Function in Patients with Anterior
      Cruciate Ligament Rupture.
AB  - Objective To explore the effect of preoperative isokinetic eccentric training
      with or not whey protein isolate supplement before operation on lower limb muscle
      strength and knee function in patients with anterior cruciate ligament (ACL)
      rupture. Methods A total of 22 male volunteers aged 18-40 years with ACL rupture
      were recruited in outpatient service. With randomized block design,subjects were
      randomly assigned to isokinetic eccentric training (IE) group and isokinetic
      eccentric training with whey protein isolate supplement (IE+WPI) group. The IE
      group received isokinetic eccentric training of the injured limb on an isokinetic
      dynamometer under the guidance of physiatrist in laboratory before operation.
      There were 3-4 sets per day with 8-10 repetitions for each set,twice a week,with
      at least one day between sessions. The IE+WPI group were supplied with whey
      protein isolate 22 g per day on the basis of isokinetic eccentric training,taking
      breakfast or 30-60 minutes after the training. The intervention lasted for 6
      weeks. Isokinetic muscle strength of limbs,the function and laxity of knee,the
      circumferences of thigh and knee,and the body composition were measured before
      and after the treatment. Results Compared with baseline,the peak torque (PT) of
      isokinetic-eccentric contraction (IE group:41.0%,P=0.018;IE+WPI
      group:46.7%,P=0.008) and the concentric contraction (IE
      group:29.6%,P=0.018;IE+WPI group:38.9%,P=0.038) of quadriceps in the two training
      groups significantly increased after isokinetic eccentric training. The Lysholm
      score increased significantly in IE+WPI group compared with baseline (P=0.018).
      Conclusions Isokinetic eccentric training before operation for ACL rupture
      patients can increase the strength of quadriceps and improve the function of
      knees. Protein isolate supplement can improve such effect.

PMID- 29338825
TI  - Efficacy of Rituximab for Patients with Chronic Lymphocytic Leukemia.
AB  - Objective To evaluate the efficacy of rituximab in treating chronic lymphocytic
      leukemia (CLL). Methods The clinical data of CLL patients receiving
      fludarabine,cyclophosphamide+/-rituximab (with or without rituximab) regimen or
      cyclophosphamide,vincristine,and prednisone+/-doxorubicin+/-rituximab regimen in
      our hospital from March 2000 to February 2015 were analyzed retrospectively.
      Therapeutic efficacies and survivals of patients treated with different regimens
      were evaluated and compared. Results The complete response (CR) rate and the
      overall response rate (ORR) in 72 patients (43.6%) treated with rituximab were
      significantly higher than those treated without rituximab (38.9% vs.
      21.5%,P=0.015;83.3% vs. 60.2%,P=0.001). The median PFS and OS for patients
      treated with rituximab were 53.0 (27.0-79.0) months and 112.0 (81.1-142.9)
      months,and the median PFS and OS for patients treated without rituximab were 28.0
      (18.3-37.7) months and 89.0(72.0-106.0),but the results were not statistically
      significant (P=0.094,P=0.109). According to the cytogenetic features,patients
      were further divided into high-risk subgroup (with chromosome 17p deletion or 11q
      deletion) and non-high-risk subgroup. And in the high-risk subgroup,the ORR of
      patients treated with rituximab was 86.4%,which was significantly higher than
      that in patients treated without rituximab (53.3%)(P=0.012);in the non-high-risk
      subgroup,the PFS was marginally prolonged in patients treated with rituximab,but
      the difference was not statistically significant(P=0.050). Conclusions Compared
      with traditional chemotherapy,the chemoimmunotherapies with rituximab result in
      higher CR rate and ORR in CLL patients. In patients without 17p deletion or 11q
      deletion,the use of rituximab can marginally prolong PFS.

PMID- 29338826
TI  - Application of the Dual-layer Spectral Detector CT in the CT Angiography of
      Superior Vena Cava.
AB  - Objective To evaluate the application of the dual-layer spectral detector CT in
      the CT angiography of superior vena cava (SVC). Methods Totally 30 consecutive
      patients who underwent chest enhanced CT in our center were enrolled in this
      study. Eight series of images were reconstructed,including the conventional
      images at 120 kVp and seven series of virtual monoenergetic spectral images at
      40,50,60,70,80,90,and 100 keV. The regions of interest (ROIs) were placed at the
      level of the proximal end,middle part,and distal end in the SVC vessel. The CT
      values and standard deviations of these three ROIs and the lipid on prothroax
      wall were measured. The signal to noise ratio (SNR),contrast to noise ratio
      (CNR),and effective dose (ED) were calculated. In addition,the quality of images
      was evaluated by two blinded readers using a grading scheme. The differences in
      CT values,SNR,and CNR among groups were analyzed using the independent t-test.
      The quality of all images was compared using non-parametric test between two
      readers,and the consistency between two radiologists were evaluated by using
      Kappa (kappa) value. Results There was no significantly different attenuation
      value among three ROIs of the SVC for each monoenergetic images (all P>0.05). The
      SVC showed significantly higher attenuation value (223.51+/-40.35)HU,SNR 13.56+/
      4.18 and CNR 24.15+/-6.58 in the 40 keV group than in other keV groups and the
      conventional group [attenuation value:(97.70+/-13.85)HU;SNR:4.59+/
      1.41;CNR:9.69+/-2.81] (P<0.005). The mean ED was(2.04+/-0.63) mSv. The subjective
      diagnostic scores accessed from two radiologists were 1 (1,2) and 1 (1,2) (Z=
      0.358,P=0.720). The subjective diagnostic quality values evaluated by two
      observers showed excellent consistency (kappa=0.863,P=0.000). Conclusion An
      optimal imaging of the SVC can be achieved on monoenergetic reconstructions at 40
      keV by using the dual-layer spectral detector CT.

PMID- 29338827
TI  - Risk Factors of Intrauterine Adhesion after Hysteroscopic Resection of
      Endometrial Polyps.
AB  - Objective To analyze the risk factors of intrauterine adhesion (IUA) after
      hysteroscopic resection of endometrial polyps. Methods Totally 359 patients
      undergoing hysteroscopic resection of endometrial polyps from January 2013 to
      December 2016 were enrolled in this study. The clinical data of IUA group and non
      IUA group were compared. Univariate analysis was performed to identify the risk
      factors of IUA,and multivariate Logistic regression analysis was further
      performed to get the independent risk factors. Results Of these 359 patients,IUA
      occured after operation in 56 patients (15.60%). Univariate analysis showed
      underlying diseases (chi2=7.381,P=0.004),multiple polyps
      (chi2=3.376,P=0.040),uterus with uterine fibroids or endometrial hyperplasia
      (chi2=6.495,P=0.009),history of curettage(chi2=31.576,P=0.000),pelvic infection
      (chi2=8.582,P=0.001),intrauterine device (chi2=7.161,P=0.006),history of cesarean
      section (chi2=5.493,P=0.014),and multigravida were (chi2=16.886,P=0.000) the risk
      factors of IUA. Logistic regression analysis showed other diseases of
      uterus(chi2=19.542,P=0.026),history of curettage (chi2=29.614,P=0.000),pelvic
      infection (chi2=5.627,P=0.002),intrauterine device (chi2=11.342,P=0.08),history
      of cesarean section(chi2=8.549,P=0.035),and multigravida (chi2=15.493,P=0.000)
      were the independent risk factors of IUA after hysteroscopic resection of
      endometrial polyps. Conclusion Other diseases of uterus,history of
      curettage,pelvic infection,intrauterine device,history of cesarean section,and/or
      multigravida can increase the risk of IUA after hysteroscopic resection of
      endometrial polyps.

PMID- 29338828
TI  - Screening Serum Differential Proteins for Childhood Asthma at Different Control
      Levels by Isobaric Tags for Relative and Absolute Quantification-based Proteomic
      Technology.
AB  - Objective To screen serum differential proteins for childhood asthma at different
      control levels,which provided the basis for the prevention and treatment of
      childhood asthma. Methods Isobaric tags for relative and absolute
      quantification,two-dimensional liquid chromatography,nanoelectrospray
      ionization,and high-resolution tandem mass spectrometry using the hybrid
      quadrupole time-of-flight platform was used to screen the differential proteins
      in serum samples from pediatric patients with controlled,partly controlled,or
      uncontrolled childhood asthma. Differential proteins were validated using enzyme
      linked immunosorbent assay (ELISA). Results A total of 260 expressed proteins
      were identified. Among them 57 differentially expressed proteins were found among
      the different control levels of childhood asthma (fold<0.8 or fold>1.2). The
      differentially expressed proteins were involved mainly in 21 biological processes
      and 8 molecular functions and were located in 17 cellular components. ELISA
      showed that the serum vitronectin level was significantly higher in controlled
      group [(573.92+/-412.43) MUg/ml] than in uncontrolled group[(382.27+/
      238.64)]MUg/ml (P=0.0399). Conclusion We identified 57 differential proteins for
      childhood asthma at different control levels,which may be used as potential
      biological targets for the control of childhood asthma.

PMID- 29338829
TI  - Imaging Findings of Common Opportunistic Infections and Malignant Tumors in
      Acquired Immunodeficiency Syndrome Patients.
AB  - The incidence of human immunodeficiency virus (HIV) infection has gradually
      increased in recent years.HIV mainly destroys the body's immune system,leading to
      decreased body resistance and thus the development of a variety of opportunistic
      infections and neoplastic diseases,especially in the digestive system.
      However,the clinical manifestations,laboratory findings,and physical examination
      results of these conditions are not specific. Imaging examinations can determine
      the presence of infection and tumor lesions and the disease
      scope;furthermore,they are useful tools for biopsy and follow-up evaluation. A
      better knowledge of the radiological findings of these diseases can enable
      radiologists to provide more information to patients and clinicians. This article
      summarize the imaging findings of common opportunistic infections and malignant
      tumors in acquired immunodeficiency syndrome patients.

PMID- 29338830
TI  - Application of Cardiopulmonary Exercise Testing in Enhanced Recovery after
      Surgery.
AB  - Enhanced recovery after surgery (ERAS) is a new perioperative concept that aims
      to reduce perioperative stress response and accelerate rehabilitation of patients
      through a variety of optimized management. With the wider application of this
      concept,the effective implementation of ERAS program has become a new challenge.
      Cardiopulmonary exercise testing (CPET) has shown promising value in the
      preoperative assessment,perioperative optimization,and postoperative
      rehabilitation of ERAS. This article reviews the application of CPET in ERAS,with
      an attempt to provide evidence for more detailed and comprehensive ERAS program.

PMID- 29338831
TI  - Diagnosis and Treatment of Acute Intermittent Porphyria.
AB  - Acute intermittent porphyria (AIP) is a metabolic disease caused by hepatic
      deficiency of hydroxymethylbilane synthase. Its clinical manifestations include
      acute abdominal pain,neuropsychological abnormalities,and red urine. Due to its
      low incidence and varied clinical symptoms,the rates of misdiagnosis and
      mistreatment were particularly high. Biochemical testing and gene detection
      contribute to diagnosis. Management strategies include intravenous administration
      of human haemin,carbohydrate loading and symptomatic treatment.

PMID- 29338832
TI  - Exhaled Air Molecules and Chronic Obstructive Pulmonary Disease.
AB  - Chronic airway inflammation,a main pathologic process of chronic obstructive
      pulmonary disease (COPD),can trigger inflammation cells and airway structure
      cells to produce bioactive molecules,which play key roles in the pathogenesis of
      COPD and are also an efficient indicators for the diagnosis and treatment of
      COPD. This article reviews the important roles of these exhaled air molecules in
      the diagnosis and treatment of COPD,with an attempt to offer new strategies in
      the management of COPD.

PMID- 29338833
TI  - Clinical Application and Development of Near-infrared Spectroscopy for Monitoring
      Regional Cerebral Oxygen Saturation.
AB  - The near-infrared spectroscopy has been applied to the continuous and noninvasive
      monitoring of regional cerebral oxygen saturation,providing information about the
      equilibrium between cerebral oxygen supply and consumption. This article reviews
      the mechanism,clinical application,and limitations of this technique.

PMID- 29338834
TI  - Advances in Tissue-engineered Oral Mucosa.
AB  - The large defect of oral and maxillofacial region doesn't only affect the
      function and aesthetics but also has an adverse impact on patients' psychology.
      The traditional way to restore the defects are limited by donor site and
      secondary trauma. In recent years,the oral mucosal tissue engineering has
      developed rapidly and provides a new solution for craniofacial reconstruction.
      Tissue-engineered oral mucosa is an ideal substitute of oral mucosa. It can be
      used in clinical settings and in vitro experiments. This articles review the
      recent advances in tissue-engineered oral mucosa and its applications.

PMID- 29338835
TI  - General health, wellbeing and oral health of patients older than 75 years
      attending health assessments.
AB  - Annual health assessments by general practices for community-dwelling people aged
      75 years and over are important for the early intervention and monitoring of
      chronic health conditions, including oral disease. Uptake of the health
      assessment to date has been poor, and little is known of the general and oral
      health profile of patients. Older patients attending health assessments at
      general practices in South Australia were sampled for this study. Data on
      demographic and socioeconomic characteristics, and patients' general and oral
      health, were collected by mailed questionnaire from 459 respondents. By
      comparison with national estimates, patients attending health assessments fared
      worse in many of the measures, such as self-rated general health, quality of life
      and the prevalence of most chronic conditions, as well as their socioeconomic
      circumstances. Also identified were a high degree of nutritional risk and clear
      need for oral health treatment, with poor self-rated oral health being three-fold
      higher than the national age-eligible population. Patients attending health
      assessments would likely benefit from nutritional screening (by a validated tool)
      and specific assessment of their oral health and dentition, supported by
      appropriate referral or intervention.

PMID- 29338836
TI  - Systems levers for commissioning primary mental healthcare: a rapid review.
AB  - Primary Health Networks (PHNs) are a new institution for health systems
      management in the Australian healthcare system. PHNs will play a key role in
      mental health reform through planning and commissioning primary mental health
      services at a regional level, specifically adopting a stepped care approach.
      Selected PHNs are also trialling a healthcare homes approach. Little is known
      about the systems levers that could be applied by PHNs to achieve these aims. A
      rapid review of academic and grey literature published between 2006 and 2016 was
      undertaken to describe the use of systems levers in commissioning primary care
      services. Fifty-six documents met the inclusion criteria, including twelve
      specific to primary mental healthcare. Twenty-six levers were identified.
      Referral management, contracts and tendering processes, and health information
      systems were identified as useful levers for implementing stepped care
      approaches. Location, enrolment, capitation and health information systems were
      identified as useful in implementing a healthcare homes approach. Other levers
      were relevant to overall health system functioning. Further work is needed to
      develop a robust evidence-base for systems levers. PHNs can facilitate this by
      documenting and evaluating the levers that they deploy, and making their findings
      available to researchers and other commissioning bodies.

PMID- 29338837
TI  - Stromule extension along microtubules coordinated with actin-mediated anchoring
      guides perinuclear chloroplast movement during innate immunity.
AB  - Dynamic tubular extensions from chloroplasts called stromules have recently been
      shown to connect with nuclei and function during innate immunity. We demonstrate
      that stromules extend along microtubules (MTs) and MT organization directly
      affects stromule dynamics since stabilization of MTs chemically or genetically
      increases stromule numbers and length. Although actin filaments (AFs) are not
      required for stromule extension, they provide anchor points for stromules.
      Interestingly, there is a strong correlation between the direction of stromules
      from chloroplasts and the direction of chloroplast movement. Stromule-directed
      chloroplast movement was observed in steady-state conditions without immune
      induction, suggesting it is a general function of stromules in epidermal cells.
      Our results show that MTs and AFs may facilitate perinuclear clustering of
      chloroplasts during an innate immune response. We propose a model in which
      stromules extend along MTs and connect to AF anchor points surrounding nuclei,
      facilitating stromule-directed movement of chloroplasts to nuclei during innate
      immunity.

PMID- 29338839
TI  - Ultrasound Assessment of a Subcutaneous Eumycetoma of the Eyebrow in an
      Immunocompromised Patient.

PMID- 29338840
TI  - Hydrogen sulfide provides intestinal protection during a murine model of
      experimental necrotizing enterocolitis.
AB  - BACKGROUND: Necrotizing enterocolitis (NEC) continues to be a morbid surgical
      condition among preterm infants. Novel therapies for this condition are
      desperately needed. Hydrogen sulfide (H2S) is an endogenous gasotransmitter that
      has been found to have beneficial properties. We therefore hypothesized that
      intraperitoneal injection of various H2S donors would improve clinical outcomes,
      increase intestinal perfusion, and reduce intestinal injury in an experimental
      mouse model of necrotizing enterocolitis. METHODS: NEC was induced in five-day
      old mouse C57BL/6 mouse pups through maternal separation, formula feeding, and
      intermittent hypoxic and hypothermic stress. The control group (n=10) remained
      with their mother and breastfed ad lib. Experimental groups (n=10/group) received
      intraperitoneal injections of phosphate buffered saline (PBS) vehicle or one of
      the following H2S donors: (1) GYY4137, 50mg/kg daily; (2) Sodium sulfide (Na2S),
      20mg/kg three times daily; (3) AP39, 0.16mg/kg daily. Pups were monitored for
      weight gain, clinical status, and intestinal perfusion via transcutaneous Laser
      Doppler Imaging (LDI). After sacrifice on day nine, intestinal appearance and
      histology were scored and cytokines were measured in tissue homogenates of
      intestine, liver, and lung. Data were compared with Mann-Whitney and p<0.05 was
      considered significant. RESULTS: Clinical score and weight gain were
      significantly improved in all three H2S-treated groups as compared to vehicle
      (p<0.05 for all groups). Intestinal perfusion of the vehicle group was 22% of
      baseline while the GYY4137 group was 38.7% (p=0.0103), Na2S was 47.0% (p=0.0040),
      and AP39 was 43.0% (p=0.0018). The vehicle group had a median histology score of
      2.5, while the GYY4137 group's was 1 (p=0.0013), Na2S was 0.5 (p=0.0004), and
      AP39 was 0.5 (p=0.0001). Cytokine analysis of the intestine of the H2S-treated
      groups revealed levels closer to breastfed pups as compared to vehicle (p<0.05
      for all groups). CONCLUSION: Intraperitoneal administration of H2S protects
      against development of NEC by improving mesenteric perfusion, and by limiting
      mucosal injury and altering the tissue inflammatory response. Further
      experimentation is necessary to elucidate downstream mechanisms prior to clinical
      implementation.

PMID- 29338838
TI  - Neuronal populations in the occipital cortex of the blind synchronize to the
      temporal dynamics of speech.
AB  - The occipital cortex of early blind individuals (EB) activates during speech
      processing, challenging the notion of a hard-wired neurobiology of language. But,
      at what stage of speech processing do occipital regions participate in EB? Here
      we demonstrate that parieto-occipital regions in EB enhance their synchronization
      to acoustic fluctuations in human speech in the theta-range (corresponding to
      syllabic rate), irrespective of speech intelligibility. Crucially, enhanced
      synchronization to the intelligibility of speech was selectively observed in
      primary visual cortex in EB, suggesting that this region is at the interface
      between speech perception and comprehension. Moreover, EB showed overall enhanced
      functional connectivity between temporal and occipital cortices that are
      sensitive to speech intelligibility and altered directionality when compared to
      the sighted group. These findings suggest that the occipital cortex of the blind
      adopts an architecture that allows the tracking of speech material, and therefore
      does not fully abstract from the reorganized sensory inputs it receives.

PMID- 29338841
TI  - The Starch Utilization System Assembles around Stationary Starch-Binding
      Proteins.
AB  - Bacteroides thetaiotaomicron (Bt) is a prominent member of the human gut
      microbiota with an extensive capacity for glycan harvest. This bacterium
      expresses a five-protein complex in the outer membrane, called the starch
      utilization system (Sus), which binds, degrades, and imports starch into the
      cell. Sus is a model system for the many glycan-targeting polysaccharide
      utilization loci found in Bt and other members of the Bacteroidetes phylum. Our
      previous work has shown that SusG, a lipidated amylase in the outer membrane,
      explores the entire cell surface but diffuses more slowly as it interacts with
      starch. Here, we use a combination of single-molecule tracking, super-resolution
      imaging, reverse genetics, and proteomics to show that SusE and SusF, two
      proteins that bind starch, are immobile on the cell surface even when other
      members of the system are knocked out and under multiple different growth
      conditions. This observation suggests a new paradigm for protein complex
      formation: binding proteins form immobile complexes that transiently associate
      with a mobile enzyme partner.

PMID- 29338842
TI  - Real-Time Nanopore-Based Recognition of Protein Translocation Success.
AB  - A growing number of new technologies are supported by a single- or multi-nanopore
      architecture for capture, sensing, and delivery of polymeric biomolecules.
      Nanopore-based single-molecule DNA sequencing is the premier example. This method
      relies on the uniform linear charge density of DNA, so that each DNA strand is
      overwhelmingly likely to pass through the nanopore and across the separating
      membrane. For disordered peptides, folded proteins, or block copolymers with
      heterogeneous charge densities, by contrast, translocation is not assured, and
      additional strategies to monitor the progress of the polymer molecule through a
      nanopore are required. Here, we demonstrate a single-molecule method for direct,
      model-free, real-time monitoring of the translocation of a disordered,
      heterogeneously charged polypeptide through a nanopore. The crucial elements are
      two "selectivity tags"-regions of different but uniform charge density-at the
      ends of the polypeptide. These affect the selectivity of the nanopore differently
      and enable discrimination between polypeptide translocation and retraction. Our
      results demonstrate exquisite sensitivity of polypeptide translocation to applied
      transmembrane potential and prove the principle that nanopore selectivity reports
      on biopolymer substructure. We anticipate that the selectivity tag technique will
      be broadly applicable to nanopore-based protein detection, analysis, and
      separation technologies, and to the elucidation of protein translocation
      processes in normal cellular function and in disease.

PMID- 29338844
TI  - SFE/SFEDP adrenal insufficiency French consensus: Introduction and handbook.
AB  - The French endocrinology society (SFE) and the French pediatric endocrinology
      society (DFSDP) have drawn up recommendations for the management of primary and
      secondary adrenal insufficiency in the adult and child, based on an analysis of
      the literature by 19 experts in 6 work-groups. A diagnosis of adrenal
      insufficiency should be suspected in the presence of a number of non-specific
      symptoms except hyperpigmentation which is observed in primary adrenal
      insufficiency. Diagnosis rely on plasma cortisol and ACTH measurement at 8am
      and/or the cortisol increase after synacthen administration. When there is a
      persistant doubt of secondary adrenal insufficiency, insulin hypoglycemia test
      should be carried out in adults, adolescents and children older than 2 years. For
      determining the cause of primary adrenal insufficiency, measurement of anti-21
      hydroxylase antibodies is the initial testing. An adrenal CT scan should be
      performed if auto-antibody tests are negative, then assay for very long chain
      fatty acids is recommended in young males. In children, a genetic anomaly is
      generally found, most often congenital adrenal hyperplasia. In the case of
      isolated corticotropin (ACTH) insufficiency, it is recommended to first eliminate
      corticosteroid-induced adrenal insufficiency, then perform an hypothalamic
      pituitary MRI. Acute adrenal insufficiency is a serious condition, a
      gastrointestinal infection being the most frequently reported initiating factor.
      After blood sampling for cortisol and ACTH assay, treatment should be commenced
      by parenteral hydrocortisone hemisuccinate together with the correction of
      hypoglycemia and hypovolemia. Prevention of acute adrenal crisis requires an
      education of the patient and/or parent in the case of pediatric patients and the
      development of educational programs. Treatment of adrenal insufficiency is based
      on the use of hydrocortisone given at the lowest possible dose, administered
      several times per day. Mineralocorticoid replacement is often necessary for
      primary adrenal insufficiency but not for corticotroph deficiency. Androgen
      replacement by DHEA may be offered in certain conditions. Monitoring is based on
      the detection of signs of under- and over-dosage and on the diagnosis of
      associated auto-immune disorders.

PMID- 29338845
TI  - Protocolized warfarin reversal with 4-factor prothrombin complex concentrate
      versus 3-factor prothrombin complex concentrate with recombinant factor VIIa.
AB  - INTRODUCTION: Life-threatening bleeding can complicate warfarin therapy. Rapid
      anticoagulant reversal via replacement of vitamin-K dependent clotting factors is
      essential for hemostasis. We compare two methods of rapid factor replacement for
      warfarin reversal. METHODS: A retrospective cohort study of warfarin-treated
      patients experiencing life-threatening bleeding who received a reversal protocol
      comprised of 4F PCC or 3F PCC and rFVIIa was performed. Demographic, clinical and
      anticoagulant reversal information, and all adverse events attributed to warfarin
      reversal were recorded. RESULTS: 195 patients were included in final analysis.
      While baseline demographics were similar between groups, the 3F-PCC group had a
      longer ICU LOS and higher in-hospital mortality (p < .01, .01). Pre-reversal INR
      was similar between both groups, but post-reversal INR was significantly lower in
      the 3F-PCC group, 0.8 versus 1.3 (p < .01). Significantly more patients
      experienced thromboembolic complications in the 3F-PCC group than the 4F-PCC
      group (p < .01). Receipt of rFVIIa was significantly associated with
      thromboembolic complications. DISCUSSION: A 4F PCC reversal strategy is
      efficacious in INR reversal and provides lower thromboembolic risk as compared to
      3F PCC with rFVIIa.

PMID- 29338846
TI  - Comparison of two trunk electromagnetic sensor placement methods during shoulder
      motion analysis.
AB  - For kinematic studies of the shoulder, electromagnetic sensors are commonly
      placed on the humerus, scapula, and trunk. The trunk sensor is used to describe
      humeral and scapular kinematics with respect to the trunk. There are two common
      trunk sensor placements, the sternum or third thoracic vertebrae (T3). It is
      currently unclear if placement of the trunk sensor affects kinematics, making it
      difficult to compare data across studies. The purpose of this study was to
      compare two trunk sensor placements (T3 and sternum) on trunk and scapular
      kinematics during arm elevation. An electromagnetic tracking system was used to
      collect kinematic data during five consecutive repetitions of ascending and
      descending arm elevation in the sagittal plane. The results indicate that trunk
      sensor placement had no significant effect on trunk kinematics or scapular
      upward/downward rotation and internal/external rotation. Scapular
      anterior/posterior tilt was significantly greater when the trunk sensor was on
      the sternum compared to the T3 vertebrae during ascending 30 degrees -120 degrees
      : mean difference = -3.51 degrees  (95%CI: -5.61, -1.40), and descending 120
      degrees -30 degrees : mean difference = -3.27 degrees  (95%CI: -6.07, -0.48).
      However, the difference in anterior/posterior tilt did not exceed the error
      (minimal detectable change), and thus is likely not a meaningful difference.
      These results indicate the trunk sensors can be affixed on T3 or the sternum,
      depending on the needs of the study.

PMID- 29338843
TI  - Current Status of Animal Models of Posttraumatic Stress Disorder: Behavioral and
      Biological Phenotypes, and Future Challenges in Improving Translation.
AB  - Increasing predictability of animal models of posttraumatic stress disorder
      (PTSD) has required active collaboration between clinical and preclinical
      scientists. Modeling PTSD is challenging, as it is a heterogeneous disorder with
      >=20 symptoms. Clinical research increasingly utilizes objective biological
      measures (e.g., imaging, peripheral biomarkers) or nonverbal behaviors and/or
      physiological responses to complement verbally reported symptoms. This shift
      toward more-objectively measurable phenotypes enables refinement of current
      animal models of PTSD, and it supports the incorporation of homologous measures
      across species. We reviewed >600 articles to examine the ability of current
      rodent models to probe biological phenotypes of PTSD (e.g., sleep disturbances,
      hippocampal and fear-circuit dysfunction, inflammation, glucocorticoid receptor
      hypersensitivity) in addition to behavioral phenotypes. Most models reliably
      produced enduring generalized anxiety-like or depression-like behaviors, as well
      as hyperactive fear circuits, glucocorticoid receptor hypersensitivity, and
      response to long-term selective serotonin reuptake inhibitors. Although a few
      paradigms probed fear conditioning/extinction or utilized peripheral immune,
      sleep, and noninvasive imaging measures, we argue that these should be
      incorporated more to enhance translation. Data on female subjects, on subjects at
      different ages across the life span, or on temporal trajectories of phenotypes
      after stress that can inform model validity and treatment study design are
      needed. Overall, preclinical (and clinical) PTSD researchers are increasingly
      incorporating homologous biological measures to assess markers of risk, response,
      and treatment outcome. This shift is exciting, as we and many others hope it not
      only will support translation of drug efficacy from animal models to clinical
      trials but also will potentially improve predictability of stage II for stage III
      clinical trials.

PMID- 29338847
TI  - Evaluation and validation of musculoskeletal force feasible set indices:
      Application to manual wheelchair propulsion.
AB  - The aim of this work was to assess handrim wheelchair propulsion effectiveness,
      related to the applied forces on the handrim, through the force feasible set. For
      a given posture of the upper-limb, it represents the set of isometric forces that
      can be applied on the handrim in any direction. The force feasible set was
      predicted from a musculoskeletal model of the upper-limb and trunk (10 degrees of
      freedom and 56 muscles). The aim of the first part of the study was to compare
      the force feasible set prediction and the force currently applied on the handrim.
      The second part proposes the creation of a new index called "Musculoskeletal
      Postural Performance Index" (MPPI) derived from the force feasible set and its
      comparison with the Mechanical Efficiency Force (MEF). These comparisons were
      conducted at 60, 80, 100, 120 and 140% of the Freely Chosen Frequency at
      submaximal and maximal conditions on 5 different phases of the push phase. The
      values of the MPPI were significantly correlated with those of the MEF. During
      the course of the push phase, the orientation of the force feasible set main axis
      approached that of the measured force and the force effectiveness evaluated
      through the MPPI increased.

PMID- 29338848
TI  - Preoperative Bevacizumab Administration in Proliferative Diabetic Retinopathy
      Patients Undergoing Vitrectomy: A Randomized and Controlled Trial Comparing
      Interval Variation.

PMID- 29338849
TI  - The Challenge of Blau Syndrome.

PMID- 29338850
TI  - Reply.

PMID- 29338851
TI  - Reply.

PMID- 29338852
TI  - Simulation-based multidisciplinary team training decreases time to critical
      operations for trauma patients.
AB  - BACKGROUND: Simulation has been promoted as a platform for training trauma teams.
      However, it is not clear if this training has an impact on health service
      delivery and patient outcomes. This study evaluates the association between
      implementation of a simulation based multidisciplinary trauma team training
      program at a metropolitan trauma centre and subsequent patient outcomes. METHOD:
      This was a retrospective review of trauma registry data collected at an 850-bed
      Level 1 Adult Trauma Centre in Sydney, Australia. Two concurrent four-year
      periods, before and after implementation of a simulation based multidisciplinary
      trauma team training program were compared for differences in time to critical
      operations, Emergency Department (ED) length of stay (LOS) and patient mortality.
      RESULTS: There were 2389 major trauma patients admitted to the hospital during
      the study, 1116 in the four years preceding trauma team training (the PREgroup)
      and 1273 in the subsequent 4 years (the POST group). There were no differences
      between the groups with respect to gender, body region injured, incidence of
      polytrauma, and pattern of arrival to ED. The POST group was older (median age 54
      versus 43 years, p < 0.001) and had a higher incidence of falls and assaults (p <
      0.001). There was a reduction in time to critical operation, from 2.63 h (IQR
      1.23-5.12) in the PRE-group to 0.55 h (IQR 0.22-1.27) in the POST-group, p <
      0.001. The overall ED LOS increased, and there was no reduction in mortality.
      Post-hoc analysis found LOS in ED was reduced in the cohort requiring critical
      operations, p < 0.001. CONCLUSION: The implementation of trauma team training was
      associated with a reduction in time to critical operation while overall ED length
      of stay increased. Simulation is promoted as a platform for training teams; but
      the complexity of trauma care challenges efforts to demonstrate direct links
      between multidisciplinary team training and improved outcomes. There remain
      considerable gaps in knowledge as to how team training impacts health service
      delivery and patient outcomes. LEVEL OF EVIDENCE: Retrospective comparative
      therapeutic/care management study, Level III evidence.

PMID- 29338853
TI  - Atypical fractures: An issue of concern or a myth?
AB  - Atypical Femoral Fractures (AFF) represent fractures located between the lesser
      trochanter and the supracondylar flare of a femur. An increasing pool of evidence
      supports their association with the prolonged use of bisphosphonates, even though
      a direct correlation is yet to be proved. The purpose of this review is to
      encapsulate the current evidence associating bisphosphonate use and the
      development of AFFs, the clinical features related to their presentation, as well
      as to report the armamentarium of strategies available in the prevention and
      treatment of AFFs. Based on these evidence, we propose a management algorithm for
      AFFs, that can serve as a guide for patients presenting with this condition.

PMID- 29338854
TI  - Long-term outcomes in cancer patients who did or did not pursue fertility
      preservation.
AB  - OBJECTIVE: To compare long-term outcomes of cancer patients who pursued fertility
      preservation (FP) with those who did not and compare random-start (RS) and
      menstrual cycle-specific (CS) protocols for FP. DESIGN: Retrospective cohort.
      SETTING: Single urban academic institution. PATIENT(S): Oncology patients who
      contacted the FP patient navigator, 2005-2015. INTERVENTION(S): None. MAIN
      OUTCOME MEASURE(S): Time to cancer treatment, disease-free survival, and
      reproductive outcomes in FP versus no-FP patients and cycle outcomes for RS
      versus CS protocols. Data were analyzed by chi2 and logistic regression.
      RESULT(S): Of 497 patients who met the inclusion criteria, 41% elected FP. The
      median number of days to cancer treatment was 33 and 19 days in the FP and no-FP
      groups, respectively. There was no difference in cancer recurrence or mortality.
      There were no differences in stimulation parameters, outcomes, or days to next
      cancer treatment in RS versus CS protocols. Twenty-one patients returned to use
      cryopreserved specimens, resulting in 16 live births. Eight of 21 returning
      patients used a gestational carrier. Thirteen FP (6.4%) and 16 no-FP (5.5%)
      patients experienced a spontaneous pregnancy. CONCLUSION(S): FP is both safe and
      efficacious for eligible cancer patients. Only 10% of patients returned to use
      cryopreserved specimens, and almost half used a gestational carrier, suggesting
      the need for further research into reproductive decision-making in cancer
      survivors.

PMID- 29338855
TI  - Vitrified blastocyst transfer cycles with the use of only vaginal progesterone
      replacement with Endometrin have inferior ongoing pregnancy rates: results from
      the planned interim analysis of a three-arm randomized controlled noninferiority
      trial.
AB  - OBJECTIVE: To assess the noninferiority of vaginal P (Endometrin) compared with
      daily intramuscular P for replacement in programmed vitrified-warmed blastocyst
      transfer cycles and to assess the noninferiority of vaginal P in combination with
      intramuscular progesterone every third day compared with daily intramuscular P.
      DESIGN: Three-arm randomized controlled noninferiority study. To enable early
      recognition of inferiority if present, an a priori interim analysis was planned
      and completed once ongoing pregnancy data were available for 50% of the total
      enrollment goal. The results of this interim analysis are presented here.
      SETTING: Assisted reproduction technology practice. PATIENT(S): Women undergoing
      transfer of nonbiopsied high quality vitrified-warmed blastocyst(s) in a
      programmed cycle. INTERVENTION(S): Vitrified-warmed blastocyst transfer with mode
      of P replacement determined by randomization to either: (1) 50 mg daily
      intramuscular P only; (2) 200 mg twice daily vaginal Endometrin; or (3) 200 mg
      twice daily Endometrin plus 50 mg intramuscular P every 3rd day. MAIN OUTCOME
      MEASURE(S): Live birth. The primary outcome of this interim analysis was ongoing
      pregnancy. RESULT(S): A total of 645 cycles were randomly assigned to one of the
      three treatment arms, received at least one dose of P replacement therapy
      according to this assignment and underwent vitrified-warmed blastocyst transfer.
      These cycles were included in the intention-to-treat analysis. The study team,
      including the statistician, were blinded to the identity of the treatment arms,
      which were randomly labeled "A," "B," and "C" in the dataset. Ongoing pregnancy
      occurred in 50%, 47%, and 31% of cycles in arms A, B, and C respectively.
      Although arm C had an rate of positive hCG equivalent to the other two arms, the
      rate of pregnancy loss for arm C was significantly higher than for either of the
      two arms, resulting in a more than one-third lower rate of ongoing pregnancy.
      There were no statistically significant differences for any outcome tested
      between arms A and B. Results of a per-protocol analysis were nearly identical to
      those of the intention-to-treat analysis. On completion of these analyses, arm C
      was revealed to be the vaginal P only arm. CONCLUSION(S): Relative to regimens
      inclusive of intramuscular P, vaginal-only P replacement for vitrified-warmed
      blastocyst transfer results in decreased ongoing pregnancy, due to increased
      miscarriage, and should be avoided. Randomization to the vaginal-only arm was
      terminated with these findings. This trial is ongoing to assess the
      noninferiority of the vaginal plus every 3rd day intramuscular P arm compared
      with daily intramuscular P in terms of live birth. CLINICAL TRIAL REGISTRATION
      NUMBER: NLM identifier NCT02254577.

PMID- 29338856
TI  - Parental health status and infant outcomes: Upstate KIDS Study.
AB  - OBJECTIVE: To assess parental health status inclusive of infertility and infant
      outcomes. DESIGN: Birth cohort with cross-sectional analysis of parental health
      status and infant outcomes. SETTING: Not applicable. PATIENT(S): Parents (n =
      4,886) and infants (n = 5,845) participating in the Upstate KIDS birth cohort.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Infertility was defined as [1]
      sexually active without contraception for 1+ years without pregnancy, [2] ever
      requiring >=12 months to become pregnant, and [3] requiring >=12 months for index
      pregnancy. Multivariable linear regression with generalized estimating equations
      estimated the change (beta coefficient and 95% confidence interval [CI]) in
      infant outcomes (gestation, birthweight, length, head circumference, ponderal
      index) and relative to each disease, including infertility after adjusting for
      age, body mass index, and infertility treatment. RESULT(S): Prevalence of
      parental chronic diseases ranged from <1% to 19%, and 21% to 54% for infertility.
      Maternal hypertension was negatively associated with gestation (beta, -0.64; 95%
      CI, -1.03, -0.25) and birthweight (-151.98; -262.30, -41.67) as was asthma and
      birthweight (-75.01; -130.40, -19.62). Maternal kidney disease was associated
      with smaller head circumference (-1.09; -2.17, -0.01), whereas paternal
      autoimmune disease was associated with larger head circumference (0.87; 0.15,
      1.60). Infertility was negatively associated with birthweight (-62.18; -103.78, 
      20.58), length (-0.33; -0.60, -0.06), and head circumference (-0.35; -0.67, 
      0.03). CONCLUSION(S): Infertility was significantly associated with reduced
      infant size even after accounting for infertility treatment, although the
      magnitude of reduction varied by definition of infertility. Absence of pregnancy
      within a year of being at risk may be informative about health.

PMID- 29338858
TI  - Cost-effectiveness analysis in cardiac surgery: A review of its concepts and
      methodologies.

PMID- 29338857
TI  - Obstetric complications after frozen versus fresh embryo transfer in women with
      polycystic ovary syndrome: results from a randomized trial.
AB  - OBJECTIVE: To evaluate the effect of frozen embryo transfer on maternal and
      neonatal complications of singleton and twin pregnancies compared with fresh
      embryo transfer in women with polycystic ovary syndrome (PCOS). DESIGN: A
      secondary analysis of a multicenter, randomized, controlled trial comparing live
      birth after frozen vs. fresh embryo transfer (FreFro-PCOS). SETTING: Reproductive
      medicine centers. PATIENT(S): A total of 1,508 patients with a diagnosis of PCOS
      who were undergoing IVF were enrolled. INTERVENTION(S): On day of oocyte
      retrieval, eligible patients were randomized to the fresh or frozen embryo
      transfer groups. Up to two embryos were transferred in both groups. All
      pregnancies were followed up until delivery. MAIN OUTCOME MEASURE(S): Gestational
      diabetes mellitus, pre-eclampsia, preterm birth, small for gestational age, and
      large for gestational age. RESULT(S): The risks of gestational diabetes mellitus,
      preterm birth, and small for gestational age were comparable between the frozen
      and fresh embryo transfer groups in both singleton and twin births. However,
      singleton infants born after frozen embryo transfer were more likely to be large
      for gestational age (25.2% vs. 17.5%; relative risk 1.44, 95% confidence interval
      1.01-2.07, P=.044) than those born after fresh embryo transfer. Twin pregnancy
      after frozen embryo transfer had a higher risk of pre-eclampsia (12.0% vs. 2.8%;
      relative risk 4.31, 95% confidence interval 1.27-14.58, P=.009) than those after
      fresh embryo transfer. CONCLUSION(S): In women with PCOS, frozen embryo transfer
      resulted in an increased risk of large for gestational age in singleton pregnancy
      and a higher risk of pre-eclampsia in twin pregnancy. CLINICAL TRIAL REGISTRATION
      NUMBER: NCT01841528.

PMID- 29338859
TI  - Renal function and outcome after heart transplantation.
AB  - OBJECTIVES: To investigate whether measured glomerular filtration rate (mGFR) is
      a risk factor for death and/or end-stage renal disease (ESRD) after heart
      transplantation (HTx). METHODS: All adult patients (n = 416) who underwent HTx
      between 1988 and 2010 were included. mGFR was performed both preoperatively and
      postoperatively as annual follow-up. Eight patients received a concomitant kidney
      transplant (KTx), and 15 underwent late KTx due to chronic renal failure after
      HTx. RESULTS: The mean drop in mGFR compared with the preoperative value was 12%
      during the first year after HTx. Preoperative mGFR was not predictive of
      mortality or ESRD. Older or the use of a ventricular assist device (VAD) were
      preoperative predictors of death. Long-term survival was significantly worse in
      the patients who experienced a >25% decrease in mGFR during the first year after
      transplantation. The need for acute postoperative renal replacement therapy (RRT)
      was associated with impaired survival but did not predict ESRD among survivors.
      On multivariable analyses, previous heart surgery, preoperative VAD, and a lower
      mGFR were all predictors of RRT. In the most recent period, death without
      previous ESRD was lower, and the only preoperative factors associated with ESRD
      by multivariable analyses were mechanical ventilation and diabetes mellitus.
      CONCLUSIONS: Pretransplantation mGFR was not predictive of mortality or ESRD
      after HTx, but necessitated simultaneous or late-stage KTx in this selected
      population of patients. However, patients with a decrease in >25% mGFR during the
      first year post-transplantation, as well as early postoperative dialysis
      dependent acute renal dysfunction, had a poor prognosis. We suggest that patients
      with severely impaired kidney function, irrespective of pretransplantation renal
      function, still should be considered for HTx, but also encourage careful
      interpretation of our results given the selection bias involved in this
      population.

PMID- 29338860
TI  - Learning curve of image-guided video-assisted thoracoscopic surgery for small
      pulmonary nodules: A prospective analysis of 30 initial patients.
AB  - OBJECTIVES: The use of image-guided video-assisted thoracoscopic surgery for
      simultaneous localization and removal of small solitary pulmonary nodules in a
      hybrid operation room using C-arm cone-beam computed tomography is gaining
      momentum. We sought to assess the effect of the learning curve on procedural
      parameters and clinical outcomes of image-guided video-assisted thoracoscopic
      surgery for treating patients with small solitary pulmonary nodules. METHODS:
      Clinical variables and treatment outcomes of the 30 initial patients with
      solitary pulmonary nodules who were treated with image-guided video-assisted
      thoracoscopic surgery at Chang Gung Memorial Hospital (Taiwan) were prospectively
      analyzed. Two sequential groups (groups I and II, n = 15 each) were compared with
      regard to localization time, radiation doses, and success rates. We used the
      Pearson's correlation coefficient to investigate the association between the
      surgical experience and the procedural time. RESULTS: In the entire cohort, the
      median size of solitary pulmonary nodules on preoperative computed tomography
      images was 6 mm (interquartile range, 4.5-9 mm), and their median distance from
      the pleural surface was 10 mm (interquartile range, 5-15 mm). The median tumor
      depth-to-size ratio was 1.4 (interquartile range, 0.7-2.5). The clinical
      parameters were similar between the 2 groups. There was an inverse association
      between the surgical experience and the procedural time (Pearson's r = -0.6873; P
      < .001). A significant reduction in localization time (median, 24 vs 49 minutes,
      respectively; P < .001) and radiation exposure (median, 70.7 vs 224 mGy,
      respectively; P < .001) was noted in group II (late patients) compared with group
      I (early patients). Notably, the success rates in groups II and I were similar
      (93.3% vs 86.7%, respectively; P = . 876). CONCLUSIONS: Our data demonstrate a
      significant learning curve for image-guided video-assisted thoracoscopic surgery
      in the treatment of solitary pulmonary nodules as evidenced by decreased
      localization time and radiation exposure occurring with increased surgical
      experience.

PMID- 29338861
TI  - Extracorporeal membrane oxygenation before surgical repair of a postinfarction
      ventricular septal defect.

PMID- 29338862
TI  - New-generation stents compared with coronary bypass surgery for unprotected left
      main disease: A word of caution.
AB  - BACKGROUND: With the advent of bare metal stents and drug-eluting stents,
      percutaneous coronary intervention has emerged as an alternative to coronary
      artery bypass grafting surgery for unprotected left main disease. However,
      whether the evolution of stents technology has translated into better results
      after percutaneous coronary intervention remains unclear. We aimed to compare
      coronary artery bypass grafting with stents of different generations for left
      main disease by performing a Bayesian network meta-analysis of available
      randomized controlled trials. METHODS: All randomized controlled trials with at
      least 1 arm randomized to percutaneous coronary intervention with stents or
      coronary artery bypass grafting for left main disease were included. Bare metal
      stents and drug-eluting stents of first- and second-generation were compared with
      coronary artery bypass grafting. Poisson methods and Bayesian framework were used
      to compute the head-to-head incidence rate ratio and 95% credible intervals.
      Primary end points were the composite of death/myocardial infarction/stroke and
      repeat revascularization. RESULTS: Nine randomized controlled trials were
      included in the final analysis. Six trials compared percutaneous coronary
      intervention with coronary artery bypass grafting (n = 4654), and 3 trials
      compared different types of stents (n = 1360). Follow-up ranged from 6 months to
      5 years. Second-generation drug-eluting stents (incidence rate ratio, 1.3; 95%
      credible interval, 1.1-1.6), but not bare metal stents (incidence rate ratio,
      0.63; 95% credible interval, 0.27-1.4), and first-generation drug-eluting stents
      (incidence rate ratio, 0.85; 95% credible interval, 0.65-1.1) were associated
      with a significantly increased risk of death/myocardial infarction/stroke when
      compared with coronary artery bypass grafting. When compared with coronary artery
      bypass grafting, the highest risk of repeat revascularization was observed for
      bare metal stents (hazard ratio, 5.1; 95% confidence interval, 2.1-14), whereas
      first-generation drug-eluting stents (incidence rate ratio, 1.8; 95% confidence
      interval, 1.4-2.4) and second-generation drug-eluting stents (incidence rate
      ratio, 1.8; 95% confidence interval, 1.4-2.4) were comparable. CONCLUSIONS: The
      introduction of new-generation drug-eluting stents did not translate into better
      outcomes for percutaneous coronary intervention when compared with coronary
      artery bypass grafting.

PMID- 29338863
TI  - In elective arch surgery with circulatory arrest, does the arterial cannulation
      site really matter? A propensity score analysis of right axillary and innominate
      artery cannulation.
AB  - OBJECTIVE: The preferred arterial cannulation site for elective proximal aortic
      procedures requiring circulatory arrest varies, and different sites have been
      tried. We evaluated the relationships between arterial cannulation site and
      adverse outcomes, including stroke, in patients undergoing elective aortic arch
      surgery. METHODS: We reviewed the records of 938 patients who underwent elective
      hemiarch or total arch surgery with circulatory arrest between 2006 and 2016.
      Five cannulation sites were used: the right axillary (n = 515; 54.9%), innominate
      (n = 376; 40.1%), and right common carotid arteries (n = 15; 1.6%), each with a
      side graft; the ascending aorta (n = 19; 2.0%); and the femoral artery (n = 13;
      1.4%). Multivariable logistic regression analysis was used to model the effects
      of cannulation site on adverse outcomes for the entire cohort and for a subcohort
      of 891 patients who underwent innominate or axillary artery cannulation.
      Propensity-matching yielded 564 patients (282 pairs) from the right axillary and
      innominate artery groups. RESULTS: For the entire cohort, mortality, stroke, and
      composite adverse outcome (operative death or persistent stroke or renal failure
      at hospital discharge) rates were 7.0%, 4.1%, and 9.8%. In the multivariable
      analysis of the axillary/innominate subcohort, cannulation site did not
      independently predict operative mortality, persistent stroke, or composite
      adverse event. These results were confirmed with the propensity-matched analysis,
      where both axillary and innominate artery cannulation provided equivalent
      composite adverse event rates, operative death rates, and overall stroke rates.
      CONCLUSIONS: During elective arch surgery, right axillary artery cannulation and
      innominate artery cannulation (both via a side graft) produce excellent results
      and can be used interchangeably.

PMID- 29338864
TI  - Mesothelioma: Live to fight another day.

PMID- 29338865
TI  - How much can you "enhance" recovery after lung resection?

PMID- 29338866
TI  - The repair of a type Ia endoleak following thoracic endovascular aortic repair
      using a stented elephant trunk procedure.
AB  - BACKGROUND: Type Ia endoleaks are not uncommon complications that occur after
      thoracic endovascular aortic repair (TEVAR). Because aortic arch vessels prevent
      extension of the landing zone, it is very difficult to manipulate a type Ia
      endoleak using an extension cuff or stent-graft, especially when the aortic arch
      is involved. Here, we retrospectively review our experience of surgical treatment
      of type Ia endoleak after TEVAR using a stented elephant trunk procedure.
      METHODS: From July 2010 to August 2016, we treated 17 patients diagnosed with a
      type Ia endoleak following TEVAR using stented elephant trunk procedure. The mean
      age of our patients was 52 +/- 8 years. The mean interval between TEVAR and the
      open surgical repair was 38 +/- 43 months. RESULTS: All cases of type Ia endoleak
      (100%) were repaired successfully. There were no in-hospital deaths. One case
      required reintubation and continuous renal replacement therapy due to renal
      failure; this patient recovered smoothly before discharge. One other patient
      suffered a stroke and renal failure and did not fully recover following
      discharge, or follow-up. During follow-up, there were 3 deaths. CONCLUSIONS:
      Acceptable results were obtained using a stented elephant trunk procedure in
      patients with a type Ia endoleak after TEVAR. This technique allowed us to repair
      the proximal aortic arch lesions, surgically correct the type Ia endoleak, and
      promote false lumen thrombosis in the distal aorta. Implantation of a stented
      elephant trunk, with or without a concomitant aortic arch procedure, is an
      alternative approach for this type of lesion.

PMID- 29338867
TI  - Validation of a definition of excessive postoperative bleeding in infants
      undergoing cardiac surgery with cardiopulmonary bypass.
AB  - OBJECTIVE: To derive and validate an objective definition of postoperative
      bleeding in neonates and infants undergoing cardiac surgery with cardiopulmonary
      bypass. METHODS: Using a retrospective cohort of 124 infants and neonates, we
      included published bleeding definitions and cumulative chest tube output over
      different postoperative periods (eg, 2, 12, or 24 hours after intensive care unit
      admission) in a classification and regression tree model to determine chest tube
      output volumes that were associated with red blood cell transfusions and surgical
      re-exploration for bleeding in the first 24 hours after intensive care unit
      admission. After the definition of excessive bleeding was determined, it was
      validated via a prospective cohort of 77 infants and neonates. RESULTS: Excessive
      bleeding was defined as >=7 mL/kg/h for >=2 consecutive hours in the first 12
      postoperative hours and/or >=84 mL/kg total for the first 24 postoperative hours
      and/or surgical re-exploration for bleeding or cardiac tamponade physiology in
      the first 24 postoperative hours. Excessive bleeding was associated with longer
      length of hospital stay, increased 30-day readmission rate, and increased
      transfusions in the postoperative period. CONCLUSIONS: The proposed standard
      definition of excessive bleeding is based on readily obtained objective data and
      relates to important early clinical outcomes. Application and validation by other
      institutions will help determine the extent to which our specialty should
      consider this definition for both clinical investigation and quality improvement
      initiatives.

PMID- 29338868
TI  - Survival and reoperation pattern after 20 years of experience with aortic valve
      sparing root replacement in patients with tricuspid and bicuspid valves.
AB  - OBJECTIVE: Remodeling or reimplantation are established operative techniques of
      aortic valve-sparing root replacement. Long-term follow-up is necessary comparing
      tricuspid and bicuspid aortic valves. METHODS: A total of 315 patients
      (tricuspid, n = 225, bicuspid, n = 89, quadricuspid, n = 1; remodeling, n = 101,
      reimplantation, n = 214) were evaluated. Mean follow-up was 10.1 +/- 5.6 and 6.4
      +/- 4.2 years for the remodeling and reimplantation group, respectively. Longest
      follow-up was 21.9 years with 99.2% completeness. Mean age of the patients was
      55.9 +/- 14.3 for the remodeling group and 48.9 +/- 14.5 years for the
      reimplantation group. RESULTS: There was no significant difference in survival
      between the remodeling and reimplantation group (P = .11). Survival was
      comparable with the normal population in the reimplantation group (P = .33). Risk
      factors for late death were age, diabetes, and a greater New York Heart
      Association classification. Cumulative incidence of reoperation at 10 years was
      5.8% for the reimplantation and 11.7% for the remodeling group (P = .65).
      Overall, there was no difference in the cumulative incidence of reoperation
      between tricuspid and bicuspid aortic valve patients (P = .13); however, a
      landmark analysis showed that in the second decade, the cumulative incidence of
      reoperation was greater in bicuspid aortic valve patients (P < .001). A total of
      10 of 11 reoperated bicuspid aortic valves were degenerated. CONCLUSIONS: The
      remodeling and reimplantation aortic valve-sparing root replacement techniques
      provided excellent long-term survival. Although the number of patients was
      relatively small, we provide some hints that in the second decade after the
      operation, especially in bicuspid aortic valve patients, the risk of reoperation
      may be increased, needing further evaluation.

PMID- 29338869
TI  - Anterior leaflet splitting during transcatheter mitral valve replacement: Killing
      two birds with one stone?

PMID- 29338870
TI  - Peptide retention prediction using hydrophilic interaction liquid chromatography
      coupled to mass spectrometry.
AB  - A model that predicts retention for peptides using a HALO(r) penta-HILIC column
      and gradient elution was created. Coefficients for each amino acid were derived
      using linear regression analysis and these coefficients can be summed to predict
      the retention of peptides. This model has a high correlation between experimental
      and predicted retention times (0.946), which is on par with previous RP and HILIC
      models. External validation of the model was performed using a set of H. pylori
      samples on the same LC-MS system used to create the model, and the deviation from
      actual to predicted times was low. Apart from amino acid composition, length and
      location of amino acid residues on a peptide were examined and two site-specific
      corrections for hydrophobic residues at the N-terminus as well as hydrophobic
      residues one spot over from the N-terminus were created.

PMID- 29338871
TI  - Likelihood of total resolution in selective comprehensive two-dimensional liquid
      chromatography with parallel processing: Simulation and theory.
AB  - The probability Pr(sLC*LC) that all peaks are separated by a resolution of 1.5 or
      more in selective comprehensive two-dimensional liquid chromatography (sLC * LC)
      is computed for simple model systems of 5 to 60 peaks and first-dimension (1D)
      gradient times of 100 to 2000 s. The computations include mimics of a commercial
      instrument, whose fixed second-dimension (2D) gradient time and use of one cycle
      time for initialization reduces Pr(sLC*LC) relative to an earlier report. For
      serial sLC * LC, in which a single device collects and transfers 1D multiplets to
      the second dimension, Pr(sLC*LC) under practical conditions is predicted to be
      only slightly larger than the probability of total resolution in LC * LC for
      separations of the same duration in each case. To increase Pr(sLC*LC), two model
      systems are proposed based on parallel processing, in which one device collects
      multiplets from the first separation while a second device simultaneously
      transfers fractions from previously collected multiplets to the second dimension
      for further separation. A sum of probabilities guideline is proposed by which
      optimal fixed 2D gradient times, ranging from 9.5 to 12 s, are found for both
      serial and parallel models. The increases of Pr(sLC*LC) based on parallel
      processing are modest; the largest is only 0.062 for one system and 0.106 for the
      other, relative to the serial model. A theory is derived that rationalizes the
      modesty of the increase, which was unexpected. It shows that Pr(sLC*LC) equals
      the probability of total resolution in the first dimension, plus the product of
      the probability that all 1D multiplets are transferred to the second dimension
      and the probability that all multiplets are separated in the second dimension.
      The theory shows that, although parallel processing is better than serial
      processing for multiplet transfer, the ability to leverage this gain is offset by
      the limited probability that all multiplets are then actually separated in the
      second dimension, which is only about 0.55 for conditions where the change from
      serial to parallel processing is most beneficial. With these findings in hand,
      two scenarios are examined for future consideration: one in which the 2D peak
      capacity is doubled, and another in which multiplets are always transferred to
      the second dimension. The latter shows considerable promise for increasing
      Pr(sLC*LC) substantially beyond its counterpart in LC * LC. For example, a 50%
      probability of separating all peaks in a 15-component mixture can be reached in
      1150 s using LC * LC. The same probability can be reached in the same time for a
      sample with nearly twice as many components (27) in the case of sLC * LC,
      assuming transfer of all multiplets to the second dimension. These findings will
      be useful to those considering systematic approaches to developing 2D-LC methods
      for moderately complex mixtures, and to those interested in instrument
      development for 2D-LC.

PMID- 29338872
TI  - Sickle cell disease: An overview of orofacial and dental manifestations.

PMID- 29338874
TI  - Extracorporeal membrane oxygenation in infants with congenital diaphragmatic
      hernia.
AB  - Congenital diaphragmatic hernia (CDH) is a severe congenital anomaly which
      impairs normal pulmonary development leading to acute and chronic respiratory
      failure, pulmonary hypoplasia, pulmonary hypertension, and mortality. CDH is the
      most common non-cardiac indication for neonatal ECMO. Prenatal and postnatal
      predictors of CDH severity aid in patient selection. Centers vary in preferred
      mode of ECMO and timing of CDH repair. Survivors of severe CDH with ECMO are at
      risk for long-term sequelae including neurodevelopmental delays.

PMID- 29338875
TI  - Computational Strategies for Exploring Circular RNAs.
AB  - Recent studies have demonstrated that circular RNAs (circRNAs) are ubiquitous and
      have diverse functions and mechanisms of biogenesis. In these studies,
      computational profiling of circRNAs has been prevalently used as an indispensable
      method to provide high-throughput approaches to detect and analyze circRNAs.
      However, without an overall understanding of the underlying strategies, these
      computational methods may not be appropriately selected or used for a specific
      research purpose, and some misconceptions may result in biases in the analyses.
      In this review we attempt to illustrate the key steps and summarize tradeoff of
      different strategies, covering all popular algorithms for circRNA detection and
      various downstream analyses. We also clarify some common misconceptions and put
      emphasis on the fields of application for these computational methods.

PMID- 29338876
TI  - Meeting report: Global vaccine and immunization research forum.
AB  - Building on the success of the first Global Vaccine and Immunization Research
      Forum (GVIRF), the World Health Organization, the National Institute of Allergy
      and Infectious Diseases, part of the National Institutes of Health in the United
      States of America, and the Bill & Melinda Gates Foundation convened the second
      GVIRF in March 2016. Leading scientists, vaccine developers, and public health
      officials from around the world discussed scientific advances and innovative
      technologies to design and deliver vaccines as well as novel tools and approaches
      to increase the uptake of vaccines throughout the world. This report summarizes
      the discussions and conclusions from the forum participants.

PMID- 29338878
TI  - Mostly "Old wine in new bottles." Reply to commentaries.

PMID- 29338877
TI  - German travelers' preferences for travel vaccines assessed by a discrete choice
      experiment.
AB  - BACKGROUND: Many travelers to regions with endemic infectious diseases do not
      follow health authorities' recommendations regarding vaccination against vaccine
      preventable infectious diseases, before traveling. The determinants of individual
      travelers' decisions to vaccinate before traveling are largely unknown. This
      study aimed to provide this information using a discrete choice experiment (DCE)
      administered to four types of German travelers: (1) business travelers; (2)
      travelers visiting friends and relatives (VFR); (3) leisure travelers; and (4)
      backpackers. METHODS: A DCE survey was developed, pretested and administered
      online. It included a series of choice questions in which respondents chose
      between two hypothetical vaccines, each characterized by four disease attributes
      with varying levels describing the of risk, health impact, curability and
      transmissibility of the disease they would prevent (described with four disease
      attributes with varying levels of risk, health impact, curability and
      transmissibility), and varying levels of four vaccine attributes (duration of
      protection, number of doses required, time required for vaccination, and vaccine
      cost). A random-parameters logit model was used to estimate the importance
      weights each traveler type placed on the various attribute levels. These weights
      were used to calculate mean monetary equivalents (MMEs) of changes in each
      attribute (holding all others constant) and of hypothetical disease-vaccine
      combinations. RESULTS: All traveler types' choices indicated that they attached
      the greatest importance to the risk and health impact of disease and to the
      vaccine cost whereas the other disease and vaccine attributes were less important
      for their decisions about travel vaccines. An option of not choosing any of the
      vaccine-pairs presented was rarely selected indicating that travelers' generally
      prefer to be vaccinated rather than not. The MMEs of changes in vaccine
      attributes indicated a very high variability between the individual travelers
      within each type. CONCLUSIONS: The travelers' responses indicated strong
      preferences for selecting vaccination rather than opting out of vaccination, and
      disease risk, health impact and vaccine cost were the most important features for
      vaccine choice.

PMID- 29338873
TI  - Opioid and Psychostimulant Plasticity: Targeting Overlap in Nucleus Accumbens
      Glutamate Signaling.
AB  - Commonalities in addictive behavior, such as craving, stimuli-driven drug
      seeking, and a high propensity for relapse following abstinence, have pushed for
      a unified theory of addiction that encompasses most abused substances. This
      unitary theory has recently been challenged - citing distinctions in structural
      neural plasticity, biochemical signaling, and neural circuitry to argue that
      addiction to opioids and psychostimulants is behaviorally and neurobiologically
      distinct. Recent more selective examination of drug-induced plasticity has
      highlighted that these two drug classes promote an overall reward circuitry
      signaling overlap through modifying excitatory synapses in the nucleus accumbens 
      a key constituent of the reward system. We discuss adaptations in
      presynaptic/postsynaptic and extrasynaptic glutamate signaling produced by
      opioids and psychostimulants, and their relevance to circuit remodeling and
      addiction-related behavior - arguing that these core neural adaptations are
      important targets for developing pharmacotherapies to treat addiction to multiple
      drugs.

PMID- 29338880
TI  - Re: Genotype-phenotype pancreatic neuroendocrine tumor relationship in multiple
      endocrine neoplasia type 1 patients: a 23-year experience at a single
      institution.

PMID- 29338879
TI  - Identifying lost surgical needles with visible and near infrared fluorescent
      light emitting microscale coating.
AB  - BACKGROUND: Retained foreign bodies (RFOs) have substantial clinical and
      financial consequences. In laparoscopic surgery, RFOs can be a cause of needing
      to convert a minimally invasive surgery (MIS) procedure to an open operation. A
      coating for surgical models was developed to augment localization of needles
      using fluorescence appropriate for open and minimally invasive surgeries
      procedures. METHODS: An epoxy matrix containing both dansyl chloride and
      indocyanine green was coated as visible and near infrared labels, respectively.
      With ultraviolet excitation, dansyl chloride emits green fluorescence and with
      NIR excitation, the ICG dye emits radiation observable with specialized near
      infrared capable laparoscopes. To evaluate the coatings, open and laproscopic
      surgeries were simulated in rabbits. Surgeons blinded to the type of needles
      (coated or non-coated) were timed while finding needles in standard conditions
      and with the use of the adjunct coatings. Control needles not located within 300
      seconds were researched with the corresponding near infrared or ultraviolet
      light. Localization time was evaluated for statistical significance, P < .05.
      RESULTS: All dual dye coated needles searched utilizing the near infrared camera
      (n = 26) or ultraviolet light (n= 26) were located within 300 seconds.
      Conversely, 9 needles in both control settings (no dye usage) were not located
      within 300 seconds. Mean time to locate control needles in open surgery and
      laparoscopic surgery was statistically 2-3* greater than time to localization
      with the use of dye as an adjunct (P = .0027 open, P < .001 laparoscopic).
      CONCLUSION: Incorporation of a dual-dye fluorescent coating on surgical needles
      improved the efficiency of locating needles, may minimize the need to convert
      minimally invasive surgeries procedures to open, and may decrease the
      consequences of a missed RFO.

PMID- 29338881
TI  - Infiltration behaviour of elemental mercury DNAPL in fully and partially water
      saturated porous media.
AB  - Mercury is a contaminant of global concern due to its harmful effects on human
      health and for the detrimental consequences of its release in the environment.
      Sources of liquid elemental mercury are usually anthropogenic, such as chlor
      alkali plants. To date insight into the infiltration behaviour of liquid
      elemental mercury in the subsurface is lacking, although this is critical for
      assessing both characterization and remediation approaches for mercury DNAPL
      contaminated sites. Therefore, in this study the infiltration behaviour of
      elemental mercury in fully and partially water saturated systems was investigated
      using column experiments. The properties affecting the constitutive relations
      governing the infiltration behaviour of liquid Hg0, and PCE for comparison, were
      determined using Pc(S) experiments with different granular porous media (glass
      beads and sands) for different two- and three-phase configurations. Results
      showed that, in water saturated porous media, elemental mercury, as PCE, acted as
      a non-wetting fluid. The required entry head for elemental mercury was higher
      (from about 5 to 7 times). However, due to the almost tenfold higher density of
      mercury, the required NAPL entry heads of 6.19cm and 12.51cm for mercury to
      infiltrate were 37.5% to 20.7% lower than for PCE for the same porous media.
      Although Leverett scaling was able to reproduce the natural tendency of Hg0 to be
      more prone than PCE to infiltrate in water saturated porous media, it
      considerably underestimated Hg0 infiltration capacity in comparison with the
      experimental results. In the partially water saturated system, in contrast with
      PCE, elemental mercury also acted as a nonwetting fluid, therefore having to
      overcome an entry head to infiltrate. The required Hg0 entry heads (10.45 and
      15.74cm) were considerably higher (68.9% and 25.8%) than for the water saturated
      porous systems. Furthermore, in the partially water saturated systems,
      experiments showed that elemental mercury displaced both air and water, depending
      on the initial water distribution within the pores. This indicates that the
      conventional wettability hierarchy, in which the NAPL has an intermediate wetting
      state between the air and the water phases, is not valid for liquid elemental
      mercury. Therefore, for future modelling of elemental mercury DNAPL infiltration
      behaviour in variably water saturated porous media, a different formulation of
      the governing constitutive relations will be required.

PMID- 29338882
TI  - [Health model, care quality and health spending public].

PMID- 29338883
TI  - Epidemiology and risk factors for chronic thromboembolic pulmonary hypertension.

PMID- 29338884
TI  - Cervical Proprioception in a Young Population Who Spend Long Periods on Mobile
      Devices: A 2-Group Comparative Observational Study.
AB  - OBJECTIVES: The purpose of this study was to evaluate if young people with
      insidious-onset neck pain who spend long periods on mobile electronic devices
      (known as "text neck") have impaired cervical proprioception and if this is
      related to time on devices. METHODS: A 2-group comparative observational study
      was conducted at an Australian university. Twenty-two participants with text neck
      and 22 asymptomatic controls, all of whom were 18 to 35 years old and spent >=4
      hours per day on unsupported electronic devices, were assessed using the head
      repositioning accuracy (HRA) test. Differences between groups were calculated
      using independent sample t-tests, and correlations between neck pain intensity,
      time on devices, and HRA test were performed using Pearson's bivariate analysis.
      RESULTS: During cervical flexion, those with text neck (n = 22, mean age +/-
      standard deviation [SD]: 21 +/- 4 years, 59% female) had a 3.9 degrees  (SD: 1.4
      degrees ) repositioning error, and the control group (n = 22, 20 +/- 1 years, 68%
      female) had a 2.9 degrees  (SD: 1.2 degrees ) error. The mean difference was 1
      degrees  (95% confidence interval: 0-2, P = .02). For other cervical movements,
      there was no difference between groups. There was a moderately significant
      correlation (P <= .05) between time spent on electronic devices and cervical pain
      intensity and between cervical pain intensity and HRA during flexion. CONCLUSION:
      The participants with text neck had a greater proprioceptive error during
      cervical flexion compared with controls. This could be related to neck pain and
      time spent on electronic devices.

PMID- 29338885
TI  - Concurrence of rheumatoid arthritis and calcium pyrophosphate deposition disease:
      A case collection and review of the literature.
AB  - OBJECTIVE: Calcium pyrophosphate deposition disease (CPDD) is arthritis caused by
      calcium pyrophosphate (CPP) crystal deposition in joints. It is commonly
      associated with aging as well as a handful of metabolic syndromes. Recent
      epidemiologic studies suggest a positive association of CPDD and rheumatoid
      arthritis (RA). Yet how these diseases are related remains unclear. We set out to
      describe 21 well-characterized patients with both diagnoses. METHODS: Medical
      records of patients with both RA and CPDD identified at a single academic
      practice site were reviewed for age, gender, age of CPDD and RA onset, disease
      duration, joint involvement, and lab values including rheumatoid factor (RF),
      cyclic citrullinated peptide antibody (CCP), iron studies, and parathyroid
      hormone and calcium levels. RESULTS: The mean age of CPDD onset was 69.5 +/- 11.4
      years, with a mean RA age onset of 53.9 +/- 16 years, demonstrating a mean lag of
      13.4 +/- 10.9 years between diagnoses. The majority of RA patients were diagnosed
      with CPDD based on the presence of radiographic chondrocalcinosis (15/21). The
      most commonly involved joint was the knee, followed by the wrist, hip, and
      shoulder. CONCLUSIONS: These data show that the diagnosis of RA often precedes
      the diagnosis of CPDD. This asynchronous presentation taken together with the
      classic age of onset for CPDD and typical pattern of joint involvement supports
      the hypothesis that CPDD develops in RA patients through similar processes as
      those that cause the idiopathic forms of this disease.

PMID- 29338886
TI  - Overweight and obesity status in pregnant women are related to intestinal
      microbiota and serum metabolic and inflammatory profiles.
AB  - BACKGROUND: Overweight and obesity may predispose women to clinical complications
      during their pregnancy. We hypothesize that a higher degree of overweight status
      is related to a range of aberrations in biomarkers already in early pregnancy.
      Our objective was to investigate whether intestinal microbiota, serum metabolic
      and inflammatory profiles differ in relation to the degree of overweight status
      in pregnant women. METHODS: This study investigated 52 overweight and 47 obese
      pregnant women in early pregnancy. Fecal samples were analyzed for intestinal
      microbiota composition by 16S ribosomal RNA gene sequencing and Qiime pipeline.
      Circulating serum metabolites, including lipids, amino acids and GlycA, a marker
      of low-grade inflammation, were analyzed by NMR metabolomics and hsCRP was
      quantified by immunoassay. Serum zonulin levels were analyzed to depict
      intestinal permeability by Zonulin ELISA kit and LPS activity for endotoxemia by
      Limulus amebocyte lysate assay. The analyses were adjusted for multiple
      comparisons using Benjamini-Hochberg procedure for false discovery rate
      controlling. RESULTS: The relative abundance of bacterial family Prevotellaceae
      (adjusted P = 0.19) and markers of low-grade inflammation, hsCRP (P = 0.0015) and
      GlycA (P < 0.001) and three branched chain amino acids (isoleucine, adjusted P =
      0.024; leucine, adjusted P = 0.026; valine, adjusted P = 0.10) and one aromatic
      amino acid (phenylalanine, adjusted P = 0.050) and concentrations of several VLDL
      particles and lipid measures in several VLDL particles were higher in obese
      pregnant women compared to their overweight pregnant counterparts (adjusted P <
      0.12). In contrast, lipid measures in a few HDL particles and many fatty acids
      were lower in obese compared to overweight pregnant women (adjusted P < 0.12).
      CONCLUSIONS: The detected alterations in intestinal microbiota and metabolic and
      inflammatory profiles related to obesity status may offer new alternative tools
      to supplement standard clinical measures to predict the risk for metabolic
      alterations during the early phase of pregnancy.

PMID- 29338887
TI  - Reply to Crivelli et al.: The different faces of fear and threat. Evolutionary
      and cultural insights.

PMID- 29338888
TI  - Vibrio communities in scleractinian corals differ according to health status and
      geographic location in the Mediterranean Sea.
AB  - The increase in seawater temperature associated with global warming is a
      significant threat to coral health and is linked to increasing mass mortality
      events and Vibrio-related coral diseases. In the Mediterranean Sea, the endemic
      Cladocora caespitosa and the invasive species Oculina patagonica are the main
      scleractinian corals affected by mass mortalities. In this study, culturable
      Vibrio spp. assemblages associated with healthy and unhealthy colonies of these
      two shallow coral species were characterized to assess the presence of Vibrio
      pathogens in tissue necrosis. Vibrio communities associated with O. patagonica
      and C. caespitosa showed geographical differences, although these became more
      homogeneous in unhealthy specimens of both species. Furthermore, the number of
      recovered Vibrio specimens was more than five times higher in unhealthy than in
      healthy corals. Within these culturable vibrios, the known pathogens Vibrio
      mediterranei and Vibrio coralliilyticus were present in unhealthy colonies of
      both coral species in the two localities, suggesting that they could play a role
      in the health status of C. caespitosa and thus act as generalist pathogens in
      Mediterranean corals. Nonetheless, a clonal type of V. coralliilyticus detected
      in C. caespitosa was not associated with disease signs, suggesting that this
      species could encompass assemblages with different levels of virulence.

PMID- 29338890
TI  - Corrigendum on "Isorhamnetin augments the anti-tumor effect of capeciatbine
      through the negative regulation of NF-kappaB signaling cascade in gastric cancer"
      [Cancer Lett. 363 (1) (2015) 28-36].

PMID- 29338889
TI  - Situational HIV stigma and stimulant use: A day-level autoregressive cross-lagged
      path model among HIV-positive gay and bisexual men.
AB  - BACKGROUND: Data on the association between HIV stigma and drug use are scarce,
      but some research suggests that internalized HIV stigma may be associated with
      increased drug use and that this association may be at least partially mediated
      by emotion dysregulation. We sought to test this hypothesis with event-level data
      to more accurately tease out the co-occurrence of these phenomena. METHODS: We
      conducted a 21-day, twice-daily ecological momentary assessment study with a
      sample of 52 HIV-positive gay and bisexual men. We utilized multivariate
      multilevel path analysis to test an autoregressive cross-lagged model of the
      direct and indirect effects of situational-level internalized HIV stigma and
      emotion dysregulation on non-prescription stimulant drug use. RESULTS: As
      hypothesized, we observed significant concurrent effects of internalized HIV
      stigma on emotion dysregulation as well as autoregressive associations of
      internalized HIV stigma and emotion dysregulation with themselves across the day.
      Furthermore, findings revealed direct effects of internalized HIV stigma on later
      emotion dysregulation and increased likelihood of stimulant use, but no direct
      effect of emotion dysregulation on stimulant use. CONCLUSIONS: Situational
      increases in internalized HIV stigma appear to exert a direct risk-enhancing
      effect on the likelihood of daily stimulant drug use and do not appear to do so
      through emotion dysregulation. Future research is needed to more carefully
      examine distinct affective experiences and regulation strategies to better
      understand what mechanism links internalized HIV stigma with drug use behaviors.

PMID- 29338891
TI  - Gray and white matter changes and their relation to illness trajectory in first
      episode psychosis.
AB  - Previous works have studied structural brain characteristics in first-episode
      psychosis (FEP), but few have focused on the relation between brain differences
      and illness trajectories. The aim of this study is to analyze gray and white
      matter changes in FEP patients and their relation with one-year clinical
      outcomes. A sample of 41 FEP patients and 41 healthy controls (HC), matched by
      age and educational level was scanned with a 3T MRI during the first month of
      illness onset. One year later, patients were assigned to two illness trajectories
      (schizophrenia and non-schizophrenia). Voxel-based morphometry (VBM) was used for
      gray matter and Tract-based spatial statistics (TBSS) was used for white matter
      data analysis. VBM revealed significant and widespread bilateral gray matter
      density differences between FEP and HC groups in areas that included the right
      insular Cortex, the inferior frontal gyrus and orbito-frontal cortices, and
      segments of the occipital cortex. TBSS showed a significant lower fractional
      anisotropy (FA) in 8 clusters that included segments of the anterior thalamic
      radiation, the left body and forceps minor of corpus callosum, the right anterior
      segment of the inferior fronto-occipital fasciculus and the anterior segments of
      the cingulum. The sub-groups comparison revealed significant lower FA in the
      schizophrenia sub-group in two clusters: the anterior thalamic radiation and the
      anterior segment of left cingulum. These findings are coherent with previous
      morphology studies. The results suggest that gray and white matter abnormalities
      are present at early stages of the disease, and white matter differences may
      distinguish different illness prognosis.

PMID- 29338892
TI  - Treatment of intraoral ranulas with a two-incision fistula technique: the
      management of recurrence.
AB  - The two-incision fistula technique for the treatment of oral ranulas has recently
      been introduced to clinical practice. We reviewed 52 patients who had recurrences
      after this treatment, and explored the possible causes and underlying mechanisms.
      A total of 13/53 ranulas had recurred, so we repeated the operation, and one
      patient had the ranula and the sublingual gland resected. We found that the thin
      mucous membrane cracked at the double incisions, which led to the formation of a
      fistula and promoted the drainage of cystic fluid. The results indicated that the
      recurrence of ranulas after the two-incision fistula technique can be reduced
      further. To avoid recurrence, the technique should be adjusted slightly,
      depending on the type of ranula present.

PMID- 29338893
TI  - The Desired Role of Health Care Providers in Guiding Older Patients With Distal
      Radius Fractures: A Qualitative Analysis.
AB  - PURPOSE: Understanding patient preferences for shared decision making is valuable
      for surgeons to advance patient-centered care, particularly in cases where there
      is not a clearly superior treatment option, like distal radius fracture. The
      existing evidence presents conflicting views on the desired role of the provider
      among older patients when making medical decisions. We aimed to investigate the
      perceived versus desired role of the provider in older adult patients with distal
      radius fracture. METHODS: Thirty patients (>=62 years old) who had sustained a
      distal radius fracture within the past 5 years were recruited from the screening
      process of the Wrist and Radius Injury Surgical Trial at the principal
      investigator's site using purposive sampling. A trained member of the research
      team conducted interviews in a semistructured format with the help of an
      interview guide. Findings were derived following the principles of grounded
      theory. RESULTS: Participants experienced varied levels of shared decision making
      with the hand surgeon. Subjects' perceived role of the surgeon did not always
      match their desired role. Most patients placed distinct trust in the
      recommendations of hand specialists regarding the technical aspects of the
      treatment. Nonetheless, respondents wanted to provide input when decisions
      pertained to outcomes or functionality. Many patients sought outside support from
      family or friends in the health care field, regardless of the outside source's
      medical specialty. CONCLUSIONS: Despite conflicting evidence, most older adult
      patients desire a shared approach when making treatment decisions. Exchanging
      information and preferences on outcomes of each treatment option may be more
      important to the patient than detailing the specific technical aspects of their
      care. CLINICAL RELEVANCE: To provide high quality care, surgeons should evaluate
      the desired role of the patient to make treatment decisions at the start of their
      interaction. Surgeons must be aware of outside medical influences that guide
      their patients' decision-making processes.

PMID- 29338894
TI  - LGBT Populations' Barriers to Cancer Care.
AB  - OBJECTIVE: To describe lesbian, gay, bisexual, and transgender (LGBT)
      individuals' barriers to accessing and receiving quality cancer care. DATA
      SOURCES: Published data on cancer care and studies of LGBT individuals.
      CONCLUSION: There is a clustering of barriers among LGBT individuals, which
      suggests multiple inequities exist in LGBT individuals' cancer care, although
      data on disparities along the cancer control continuum are not consistently
      available. IMPLICATIONS FOR NURSING PRACTICE: Nurses can make a difference in
      LGBT individuals' cancer care by obtaining training on LGBT health and their
      cancer-related needs and by providing a welcoming and respectful relationship
      with LGBT patients.

PMID- 29338895
TI  - Feasibility of total intravenous anesthesia by cardiologists with the support of
      anesthesiologists during catheter ablation of atrial fibrillation.
AB  - BACKGROUND: The optimal methodology for sedation and anesthesia during atrial
      fibrillation (AF) ablation has not been well established. We assessed the
      feasibility of total intravenous anesthesia (TIVA) by cardiologists with support
      from anesthesiologists during AF ablation and quality of pulmonary vein isolation
      (PVI) and single procedure success rate at 12 months. METHODS: TIVA was performed
      by cardiologists using IV propofol and fentanyl under controlled ventilation via
      i-gelTM without neuromuscular blocking drugs in 160 consecutive patients (80
      nonparoxysmal) with no anticipated difficult airway or other severe diseases.
      Anesthesiologists were requested to be on standby during the procedure. The
      incidence of anesthesia-associated complications and ablation-associated
      complications were assessed. To evaluate the quality of PVI, the prevalence of
      acute adenosine triphosphate (ATP)-provoked PV reconnections and late PV
      reconnections among those requiring a redo procedure was analyzed. RESULTS: TIVA
      was successfully completed in 152 patients (95%). In five (3%), we requested help
      from anesthesiologists, and in three (2%), TIVA was abandoned. No major
      anesthesia-associated complications were observed. Ablation-associated
      complications were observed in seven patients (4%). ATP provocation test was
      performed in 141 patients, and no acute PV reconnections were observed in 134
      (95%). Success rates at 12 months were 85% of patients off antiarrhythmic drugs.
      Twenty-one of 24 patients with recurrence underwent a redo session, and 18 (86%)
      had no PV reconnections. CONCLUSIONS: TIVA by cardiologists with support from
      anesthesiologists during AF ablation may be feasible. The success rate at 12
      months was high, and prevalence of acute and late PV reconnection was very low.

PMID- 29338896
TI  - Novel bioabsorbable polymer and polymer-free metallic drug-eluting stents.
AB  - The introduction of drug-eluting stents (DES) significantly reduced angiographic
      restenosis and the clinical need for revascularization following percutaneous
      coronary intervention. However, concerns remain regarding the long-term safety
      and efficacy of DES. The use of durable polymers for drug elution that have
      limited biocompatibility is thought to contribute toward DES failure, by
      promoting an adverse local inflammatory response and vascular toxicity.
      Biodegradable polymer and polymer-free metallic stents represent two novel
      technological solutions to this challenging clinical problem. This review
      summarizes the available clinical evidence supporting the use of either
      biodegradable polymer or polymer-free DES platforms.

PMID- 29338898
TI  - Acute Respiratory Failure Due to Chronic Tophaceous Gout With Laryngeal and
      Bronchial Involvement: An Unusual Complication.

PMID- 29338897
TI  - Asymptomatic bacteriuria and urinary tract infection in pregnant women with and
      without diabetes: Cohort study.
AB  - OBJECTIVE: To compare the prevalence of asymptomatic bacteriuria (ASB) and the
      incidence of urinary tract infection (UTI) in pregnant women with and without
      diabetes mellitus (DM) or gestational DM (GDM). STUDY DESIGN: We performed a
      cohort study in five hospitals and two midwifery clinics in the Netherlands.
      Pregnant women with and without DM or GDM were screened for the presence of ASB
      around 12 and 32 weeks' gestation. Characteristics of participants as well as
      outcome data were collected from questionnaires and medical records. ASB was
      defined as the growth of at least 10e5 cfu/ml isolated from the urine of a woman
      without UTI complaints. UTI was considered to be present when a treating
      physician had diagnosed UTI and prescribed antibiotics. RESULTS: We studied 202
      women with and 272 women without DM or GDM. Of all women 31.7% with and 94.9%
      without DM or GDM provided a week 12 sample. The prevalence of ASB was comparable
      in women with and without DM or GDM (12 weeks' n = 322; 4.7% and 2.3%; relative
      risk (RR) 2.02; 95% confidence interval (CI) 0.52-7.84; 32 weeks' n = 422; 3.2%
      and 3.0%; RR 1.06; 95% CI 0.36-3.09), as was the incidence of UTI (16.8% and
      12.9%; RR 1.31; 95% CI 0.85-2.02). Neither ASB nor UTI were associated with
      preterm birth or babies being small for gestational age. CONCLUSION: In pregnant
      women with and women without DM or GDM, the overall prevalence of ASB was low.
      Neither ASB nor UTI did differ significantly between the groups. Our data
      discourage a routine ASB screen and treat policy in pregnant women with DM or
      GDM.

PMID- 29338899
TI  - Hyponatremia in COPD: a Little Known Complication.

PMID- 29338900
TI  - Noninvasive ventilation failure in pneumonia patients >=65years old: The role of
      cough strength.

PMID- 29338901
TI  - High degree heart block following suicide attempt by hanging.

PMID- 29338902
TI  - Stage-specific expression of DDX4 and c-kit at different developmental stages of
      the porcine testis.
AB  - Spermatogenesis begins with spermatogonial stem cells (SSCs), which are located
      in the basement membrane of the adult testes. Previous studies have described
      specific biomarkers for undifferentiated porcine spermatogonia or SSCs; however,
      these markers are not sufficient to understand spermatogenesis at different
      developmental stages. The objective of this study was characterize the expression
      of DEAD-Box polypeptide 4 (DDX4, also known as VASA) and tyrosine-protein kinase
      kit (c-kit), as potential markers of male germ cells in the porcine testis. In
      porcine testis tissue at prepubertal stages (5, 30, and 60 days), DDX4 and c-kit
      protein expression was detected in the most undifferentiated spermatogonia, which
      also express protein gene product 9.5 (PGP9.5). However, in porcine testis
      tissues from pubertal and postpubertal stages (90, 120, and 150 days), DDX4 and c
      kit were not detected in PGP9.5-positive undifferentiated spermatogonia. The DDX4
      expression pattern was similar to that of c-kit in the porcine testis. In adult
      porcine testes, DDX4-expressing cells were located on the lumenal side, compared
      to synaptonemal complex protein 3-positive primary spermatocytes, but DDX-4 was
      not co-expressed with acrosin, a known acrosome marker. In addition, DDX4 was
      detected in PGP9.5-expressing porcine SSCs in culture. Based on our results, we
      suggest that DDX4 and c-kit are putative markers of undifferentiated
      spermatogonia in the prepubertal porcine testis. While in the postpubertal
      porcine testis, they are markers of differentiated spermatocytes. These findings
      may facilitate future studies of porcine spermatogenesis.

PMID- 29338903
TI  - Clinical workflow optimization to improve 4DCT reconstruction for Toshiba
      Aquilion CT scanners.
AB  - Respiratory motion remains a source of major uncertainties in radiotherapy.
      Respiratory correlated computed tomography (referred to as 4DCT) serves as one
      way of reducing breathing artifacts in 3D-CTs and allows the investigation of
      tumor motion over time. The quality of the 4DCT images depends on the data
      acquisition scheme, which in turn is dependent on the vendor. Specifically, the
      only way Toshiba Aquilion LB CT scanners can reconstruct 4DCTs is a cycle-based
      reconstruction using triggers provided by an external surrogate signal. The
      accuracy is strongly dependent on the method of trigger generation. Two
      consecutive triggers are used to define a breathing cycle which is divided into
      respiratory phases of equal duration. The goal of this study is to identify if
      there are advantages in the usage of local-amplitude based sorting (LAS) of the
      respiration motion states, in order to reduce image artifacts and improve 4DCT
      quality. Furthermore, this study addresses the generation and optimization of a
      clinical workflow using as surrogate motion monitoring system the SentinelTM (C
      RAD AB, Sweden) optical surface scanner in combination with a Toshiba Aquilion LB
      CT scanner. For that purpose, a phantom study using 10 different breathing
      waveforms and a retrospective patient study using the 4DCT reconstructions of 10
      different patients has been conducted. The error in tumor volume has been reduced
      from 2.9+/-3.7% to 2.7+/-2.6% using optimal cycle-based triggers (manipulated
      CBS) and to 2.7+/-2.2% using LAS in the phantom study. Moreover, it was possible
      to decrease the tumor volume variability from 5.0+/-3.6% using the original cycle
      based triggers (original CBS) to 3.5+/-2.5% using the optimal triggers and to
      3.7+/-2.7% using LAS in the patient data analysis. We therefore propose the usage
      of the manipulated CBS, also with regard to an accurate and safe clinical
      workflow.

PMID- 29338904
TI  - Pain and its Impact on the Functional Ability in Children Treated at the
      Children's Cancer Center of Lebanon.
AB  - PURPOSE: The purpose of this study was to describe the characteristics of pain in
      children under treatment at the Children Cancer Centre of Lebanon at the American
      University of Beirut Medical Centre. Design and Methods A cross-sectional
      correlational survey was used. The Adolescent Pediatric Pain Tool and the
      Functional Disability Inventory were used to examine the characteristics of pain
      experienced in a consecutive sample of children treated at the CCCL and its
      impact on their functional abilities. RESULTS: The mean age of the 62
      participants was 12.3 (SD 2.9). The overall mean pain intensity rating for the
      sample was 5.06 (SD 1.87) on a 10 cm Word Graphic Rating Scale. More than one
      half of the children in the sample (57.4%) reported having pain "sometimes" with
      a median duration of two hours per pain episode. The most frequently reported
      locations of pain were the forehead, the abdomen, and the lower back. For the
      most part, the children used sensory words to describe their pain experience. The
      children reported moderate levels of functional disability (mean FDI score 25.04,
      SD 13.81). Multivariable linear regression analysis identified frequency,
      duration, location, use of affective descriptors, and treatments as statistically
      significant predictors of pain intensity. CONCLUSION: Regrettably, the findings
      reported attest once again to unrelieved pain in a pediatric oncology population.
      PRACTICE IMPLICATIONS: Policy makers can contribute to pain control by
      introducing legislation and national policies to ensure adequate pain management
      for children with cancer in Lebanon.

PMID- 29338905
TI  - Posterior Reversible Encephalopathy Syndrome: A Rare Childhood Case with
      Unconsciousness.
AB  - BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is a condition
      characterized by seizures, altered consciousness, visual disturbances, and
      headache. Characteristic findings on neuroimaging include cerebral edema,
      typically involving the parieto-occipital white matter. PRES has been associated
      with hypertension, autoimmune disease, and Henoch-Scholein purpura (HSP), but few
      cases have been reported, and fewer cases of PRES have been reported in children.
      CASE REPORT: We report the case of a 4-year-old girl who presented with blindness
      and semi-consciousness. The patient had no significant medical history and no
      abnormalities on physical examination or laboratory testing, although she had
      slightly elevated blood pressure. After hospitalization, the patient showed some
      characteristic signs of HSP and cranial magnetic resonance imaging revealed PRES
      as the cause of semi-consciousness. In our discussion, we examine the clinical
      features of PRES and remarkable points for the clinical diagnosis and management
      of this rare but important disease. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF
      THIS?: Although reports of PRES in children are rare, PRES should be considered
      in the differential diagnosis of children presenting with disturbance of
      consciousness. Emergency physicians should consult with pediatric physicians to
      confirm diagnoses of PRES and determine an appropriate treatment plan, given its
      variable etiology. Measurements of blood pressure, which are often missing in
      pediatric cases, can help physicians to arrive at a correct diagnosis.

PMID- 29338906
TI  - Virtual computed tomography morphometry of the patella for estimation of sex
      using postmortem Japanese adult data in forensic identification.
AB  - In forensic anthropological identification of human remains and single bones,
      computed tomography (CT) data analysis facilitates volumetric and radiographic
      density analyses, and a recently developed automated analysis system markedly
      improved the performance, accuracy, and reproducibility of three-dimensional (3
      D) reconstruction. The present study aimed to investigate virtual CT morphometry
      of the patella for the estimation of sex using postmortem CT data of forensic
      autopsy cases of Japanese individuals aged >=18 years (total n=220; 110 males and
      110 females; estimated postmortem interval <88h), especially with regard to the
      efficacy of 3-D bone volumetry. Sex-related differences were detected for all
      parameters (males>females; p<0.0001), but the differences were the most notable
      for bone mass volume; the estimated cut-off values (cm3) for discriminating males
      and females were 20.35 with a sensitivity and specificity of 0.85 and 0.91 for
      the left side and 19.96 with a sensitivity and specificity of 0.83 and 0.92 for
      the right side, respectively. The mean CT value showed an age-dependent decrease
      and was particularly low in females aged >60years. These findings indicate the
      efficacy of virtual CT morphometry of the patella using an automated analyzer for
      sex estimation.

PMID- 29338907
TI  - New photodynamic molecular beacons (PMB) as potential cancer-targeted agents in
      PDT.
AB  - Further improvements in Photodynamic therapy (PDT) necessitate that the dye
      targets more selectively tumour tissues or neovascularization than healthy cells.
      Different enzymes such as matrix metalloproteinases (MMPs) are overexpressed in
      tumour areas. Among these MMPs, gelatinases (MMP-2 and MMP-9) and its activator
      MMP-14 are known to play a key role in tumour angiogenesis and the growth of many
      cancers such as glioblastoma multiforme (GBM), an aggressive malignant tumour of
      the brain. These last years, the concept of photodynamic molecular beacons (PMB)
      became interesting for controlling the photosensitizer's ability to generate
      singlet oxygen (1O2) close to target biomolecules as MMPs. We report herein novel
      PMBs triggered by MMP-2 and/or MMP-9 and/or MMP-14, comprising a photosensitizer
      and a singlet oxygen quencher linked by MMP cleavable peptide linker (H
      GRIGFLRTAKGG-OH). First of all, we focused on the synthesis and the photophysical
      study of different derivatives photosensitizer-peptide. This preliminary work
      concluded on an influence of the nature and the distance from the peptide, but
      not of the position of the photosensitizer in these derivatives on the
      proteolytic enzymatic action. The nature of the quencher used (a blackberry
      quencher (BBQ-650) or a black hole quencher (BHQ3)) does not influence the
      enzymatic action. We also studied the influence of an additional PEG spacer.
      Finally, the synthesis, the singlet oxygen quenching efficiency and the enzymatic
      activation of these new MMP- cleavable-PMBs were compared.

PMID- 29338908
TI  - Relationship between neuropathy proximal to the suprascapular nerve and rotator
      cuff tear in a rodent model.
AB  - BACKGROUND: Rotator cuff tears are believed to coexist with cervical spine
      lesions. In cases of preexisting neuropathy, such as cervical spine lesions,
      fatty degeneration has likely already occurred due to the neuropathy. In these
      cases, rotator cuff tear is thought to occur easily because of preexisting
      extensive fatty degeneration and degeneration of the tendons due to neuropathy.
      This study aimed to evaluate the effects of paralysis due to neuropathy proximal
      to the suprascapular nerve on the supraspinatus and infraspinatus tendons using a
      rat model of brachial plexus paralysis. METHODS: This study included fifteen, 8
      week-old Sprague-Dawley rats. The left shoulder was included in the paralysis
      group and the contralateral shoulder constituted the sham group. Biomechanical
      testing (evaluated maximum tear force, maximum displacement and Young's modulus)
      (n = 10) and histological analyses (n = 5) (using the Bonar scale) were performed
      at 12 weeks postoperatively to confirm the degeneration of the tendon. RESULTS:
      The mean maximum tear force was significantly lower in the paralysis group than
      in the sham group (P = 0.008), indicating that rotator cuff tears occurred with a
      lower force in the paralysis group. Additionally, the average Young's modulus was
      significantly greater in the paralysis group than in the sham group (P = 0.003),
      indicating that the rotator cuff muscle became hard and inflexible in the
      paralysis group. The Bonar scales of the histological analyses were significantly
      higher in the paralysis group (total score = 7.04 +/- 0.61) than the sham group
      (total score = 0) (p < 0.0001). CONCLUSIONS: If neuropathy of proximal to the
      suprascapular nerve, such as cervical spine or brachial plexus lesion, exists,
      weakness and degeneration of the rotator cuff tendon and stiffness of the rotator
      cuff muscle develop. Neuropathy is likely a cause of rotator cuff tears.

PMID- 29338909
TI  - Essential structure of orexin 1 receptor antagonist YNT-707, Part II: Drastic
      effect of the 14-hydroxy group on the orexin 1 receptor antagonistic activity.
AB  - The 14-dehydration- and 14-H derivatives of the orexin 1 receptor (OX1R)
      antagonist YNT-707 (2) were synthesized. The obtained derivatives showed higher
      affinities for OX1R than the corresponding 14-hydroxy derivatives. The
      conformational analysis suggested that the 17-sulfonamide groups in the
      derivatives without the 14-hydroxy group have a greater tendency to be oriented
      toward the upper side of the D-ring compared with the 14-hydroxy derivatives.
      Additionally, the 14-dehydration-derivative with 6alpha-amide side chain showed
      significantly higher affinity than the 14-hydroxy derivative, while the
      corresponding 14-H derivative showed only slightly higher affinity. Thus, the 14
      hydroxy group strongly affects the affinity of the antagonist for the OX1R.

PMID- 29338910
TI  - Synthesis of deuterium-labelled analogues of NLRP3 inflammasome inhibitor MCC950.
AB  - This study describes the syntheses of di, tetra and hexa deuterated analogues of
      the NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome
      inhibitor MCC950. In di and tetra deuterated analogues, deuteriums were
      incorporated into the 1,2,3,5,6,7-hexahydro-s-indacene moiety, whereas in the
      hexa deuterated MCC950 deuteriums were incorporated into the 2-(furan-3-yl)propan
      2-ol moiety. The di deuterated MCC950 analogue was synthesised from 4-amino
      3,5,6,7-tetrahydro-s-indacen-1(2H)-one 5. Tetra deuterated analogues were
      synthesised in 10 chemical steps starting with 5-bromo-2,3-dihydro-1H-inden-1-one
      9, whereas the hexa deuterated analogue was synthesised in four chemical steps
      starting with ethyl-3-furoate 24. All of the compounds exhibited similar activity
      to MCC950 (IC50 = 8 nM). These deuterated analogues are useful as internal
      standards in LC-MS analyses of biological samples from in vivo studies.

PMID- 29338911
TI  - Rosette-forming glioneuronal tumor of the fourth ventricle. Two cases report and
      literature review.
AB  - Rosette-forming glioneuronal tumor of the fourth ventricle is a primary central
      nervous system tumor introduced in the group of glioneuronal tumors in the WHO
      classification of 2007. Initially it was described around the fourth ventricle,
      but recently have been published cases in different locations. We present 2cases
      of this rare tumor, both surgically treated. The first in a 41 year old man with
      typical symptoms of posterior fossa injury. The second in an 18 year old woman,
      with incidental finding of posterior fossa injury that was also surgically
      treated. We present pre- and post-surgical magnetic resonance images,
      histological pictures of this tumor and we make a review of the literature.

PMID- 29338912
TI  - Surgical outcomes of traumatic cervical fractures in patients with ankylosing
      spondylitis.
AB  - OBJECTIVE: Ankylosing spondylitis is an inflammatory rheumatic disease mainly
      affecting the axial skeleton. The rigid spine may secondarily develop
      osteoporosis, further increasing the risk of spinal fracture. In this study, we
      reviewed fractures in patients with ankylosing spondylitis that had been
      clinically diagnosed to better define the mechanism of injury, associated
      neurological deficit, predisposing factors, and management strategies. METHODS:
      Between January 2004 and December 2014, 6 patients with ankylosing spondylitis
      and neurological complications after injuries were treated. Neuroimaging
      evaluation was obtained in all patients by using plain radiography, CT scan, and
      MR imaging. The ASIA Impairment Scale was used in order to evaluate the
      neurologic status of the patients. Surgical decision was based on relationship of
      neurological involvement and spinal instability. RESULTS: A total of 6 cervical
      injuries were identified in a review of patients in whom ankylosing spondylitis
      had been diagnosed. Of these, 2 patients were associated with a hyperextension
      mechanism and 4 cases by flexion mechanism. Posttraumatic neurological deficits
      were demonstrated in all 6 cases and neurological improvement after surgery was
      observed in 4 of these cases. The two cases were not improved by the surgery was
      on a case by presenting a degree of Asia A and another patient who initially
      improved with surgery but died of pneumonia in the postoperative. CONCLUSIONS:
      Patients with ankylosing spondylitis are highly susceptible to spinal fracture
      and spinal cord injury even after only mild trauma. Initial CT or MR imaging of
      the whole spine is recommended even if the patient's symptoms are mild. The
      patient should also have early surgical stabilization to correct spinal deformity
      and avoid worsening of the patient's neurological status.

PMID- 29338913
TI  - Discrepancies in staging, treatment, and delays to treatment may explain
      disparities in bladder cancer outcomes: An update from the National Cancer Data
      Base (2004-2013).
AB  - INTRODUCTION: We sought to characterize national disparities in the diagnosis of
      advanced stage bladder cancer. Among patients with advanced disease, we explored
      disparities in overall survival, treatment, and time to treatment. METHODS AND
      MATERIALS: We queried the National Cancer Data Base for patients diagnosed with
      bladder urothelial carcinoma. We used multivariable logistic regression to assess
      the association between covariates and diagnosis of advanced disease (AJCC stage
      III-IV). We used Kaplan-Meier, log-rank, and Cox proportional analyses to
      evaluate disparities in overall survival for patients with advanced disease.
      Receipt of treatment and delays to treatment were compared between subgroups.
      RESULTS: Among our cohort of 328,560 patients, 7.6% were diagnosed with advanced
      disease. Female sex, black race, Hispanic ethnicity, and living in a region of
      lower income and education were all associated with increased odds of advanced
      disease. Female sex (HR = 1.16; 95% CI: 1.12-1.20; P<0.001), black race (HR =
      1.10; 95% CI: 1.04-1.18; P = 0.002), and lower regional income levels (fourth
      quartile compared to first: HR = 1.08; 95% CI: 1.02-1.16; P = 0.016) portended
      worse overall survival. Chemotherapy (HR = 0.55, 95% CI: 0.53-0.57; P<0.001) and
      radical cystectomy (HR = 0.61; 95% CI: 0.59-0.64, P<0.001) improved survival.
      Females, black patients, and patients from regions of lower income and education
      were less likely to receive treatment and less likely to receive treatment within
      12 weeks of diagnosis. CONCLUSION: There are several disparities in the diagnosis
      and treatment of advanced bladder cancer. Overall survival for certain groups may
      benefit from earlier diagnosis and improved timely access to potentially life
      prolonging treatment.

PMID- 29338914
TI  - Prophylactic antibiotics following radical cystectomy reduces urinary tract
      infections and readmission for sepsis from a urinary source.
AB  - INTRODUCTION: Urinary tract infections (UTI) and sepsis contribute significantly
      to the morbidity associated with cystectomy and urinary diversion in the first 30
      days. We hypothesized that continuous antibiotic prophylaxis decreased UTIs in
      the first 30 days following radical cystectomy. METHODS: Patients with urothelial
      carcinoma of the bladder who underwent a radical cystectomy with urinary
      diversion for bladder cancer at Oregon Health and Science University from January
      2014 to May 2015 were included in the study. The ureteral stents were kept for 3
      weeks in both groups. In October 2014, we enacted a Department Quality Initiative
      to reduce UTIs. Following the initiative, all radical cystectomy patients were
      discharged home on antibiotic prophylaxis following a postoperative urine culture
      obtained during hospitalization. To evaluate the effectiveness of the initiative,
      the last 42 patients before the initiative were compared to the first 42 patients
      after the initiative with regard to the rate of UTI in the first 30 days
      following surgery. We used a combination of comprehensive chart review and the
      American College of Surgeons' National Surgical Quality Improvement Program
      (NSQIP) to determine UTI and readmission for urosepsis in the first 30 days
      following surgery. This ensured accurate capture of all patients developing a
      UTI. RESULTS: A total of 12% in the prophylactic antibiotic group had a
      documented UTI, whereas 36% in the no antibiotic group had a urinary tract
      infection (P<0.004). A total of 1 (2%) patient in the antibiotic group was
      readmitted for urosepsis whereas 7 (17%) patients in the no antibiotic group were
      admitted for urosepsis (P = 0.02). There was no association noted between urine
      culture at discharge and the development of UTI in the 30-day postdischarge
      period (P = 0.75). The median time to UTI was 19 days and the most common
      organism was Enterococcus (32%). Thirty-percent of patients not receiving
      prophylaxis developed a UTI 1 day after ureteral stent removal. No patients had a
      UTI following stent removal in the prophylaxis group. No adverse antibiotic
      related events were noted. CONCLUSION: Prophylactic antibiotics in the 30 days
      following radical cystectomy is associated with a significant decrease in urinary
      tract infections and readmission from urosepsis after surgery.

PMID- 29338915
TI  - The significance of avoiding household food waste - A means-end-chain approach.
AB  - Many humans suffer from hunger, while edible food is discarded. This study aims
      at showing the importance of avoiding food waste in households and its causes by
      applying the means-end-chain analysis. Additional the means-end-chain approach
      should be examined in how far the method is suitable to get insights towards this
      topic. Consumer backgrounds in terms of feelings and attitudes regarding food
      waste should be shown, with the particular question why food waste personally is
      important. The data collection occurred utilizing the hard laddering method
      within a quantitative online survey. The results indicate that avoiding food
      waste is important for the greater part of consumers, as many claim to have a bad
      conscience, seeing it as morally wrong and reprehensible to waste food. A sample
      breakdown of gender, age and income points differences among these groups in
      regards to psychological consequences and value systems. Financial and
      environmental aspects have a lesser impact on attitudes and feelings regarding
      food waste in households.

PMID- 29338916
TI  - Patent foramen ovale closure vs. medical therapy for recurrent stroke prevention:
      Evolution of treatment effect during follow-up.
AB  - BACKGROUND: Little is known regarding changes in treatment effect over time
      associated with patent foramen ovale (PFO) closure among patients with embolic
      stroke of unknown origin. METHODS: We reconstructed Kaplan-Meier curves for
      stroke from individual randomized trials comparing PFO closure vs. medical
      therapy among patients with embolic stroke. Random effects Cox-regression
      analyses were performed in order to estimate hazard ratios (HRs) with 95%
      confidence intervals (95%CIs). RESULTS: A total of 2531 patients enrolled across
      4 randomized trials were included. PFO closure was associated with a significant
      reduction in the risk of stroke at longest available follow-up (HR 0.18, 95%CI
      0.06 to 0.59, P=0.005). However, recurrent stroke was already significantly
      reduced among patients randomized to PFO closure at 1-year (HR 0.40, 95%CI 0.20
      to 0.80, P=0.010), with the treatment effect remaining consistent (P-for
      interaction=0.356) between 1- and 5-year (HR 0.14, 95%CI 0.05 to 0.55, P=0.005)
      and beyond 5-year (HR 0.20, 95%CI 0.03 to 1.19, P=0.077). CONCLUSIONS: Among
      patients with embolic stroke of unknown origin, PFO closure reduces the risk of
      stroke compared with medical therapy, with a significant reduction in recurrences
      starting already within 1-year after percutaneous PFO closure.

PMID- 29338917
TI  - Exercise training in adults with repaired tetralogy of Fallot: A randomized
      controlled pilot study of continuous versus interval training.
AB  - INTRODUCTION: Adults with repaired tetralogy of Fallot (ToF) have impaired
      exercise capacity, vascular and cardiac autonomic function, and quality of life
      (QoL). Specific effects of high-intensity interval or moderate continuous
      exercise training on these parameters in adults with repaired ToF remain unknown.
      METHODS AND RESULTS: Thirty adults with repaired ToF were randomized to either
      high-intensity interval, moderate intensity continuous training (36 sessions, 2-3
      times a week) or usual care (no supervised exercise). Exercise capacity, flow
      mediated vasodilation, pulse wave velocity, NT-proBNP and fibrinogen levels,
      heart rate variability and recovery, and QoL (SF-36 questionnaire) were
      determined at baseline and after the intervention period. Twenty-seven patients
      (mean age 39+/-9years, 63% females, 9 from each group) completed this pilot
      study. Both training groups improved in at least some parameters of
      cardiovascular health compared to no exercise. Interval-but not continuous
      training improved VO2peak (21.2 to 22.9ml/kg/min, p=0.004), flow-mediated
      vasodilation (8.4 to 12.9%, p=0.019), pulse wave velocity (5.4 to 4.8m/s,
      p=0.028), NT-proBNP (202 to 190ng/L, p=0.032) and fibrinogen levels (2.67 to
      2.46g/L, p=0.018). Conversely, continuous-but not interval-training improved
      heart rate variability (low-frequency domain, 0.32 to 0.22, p=0.039), heart rate
      recovery after 2min post-exercise (40 to 47 beats, p=0.023) and mental domain of
      SF-36 (87 to 95, p=0.028). CONCLUSION: Both interval and continuous exercise
      training modalities were safe. Interval training seems more efficacious in
      improving exercise capacity, vascular function, NT-proBNP and fibrinogen levels,
      while continuous training seems more efficacious in improving cardiac autonomic
      function and QoL. (Clinicaltrials.gov, NCT02643810).

PMID- 29338918
TI  - Filling pressures in Fontan revisited: Comparison between pulmonary artery wedge,
      ventricular end-diastolic, and left atrial pressures in adults.
AB  - BACKGROUND: Pulmonary artery wedge pressure (PAWP) has been shown to correlate
      better with left atrial pressure (LAP) than ventricular end-diastolic pressure
      (VEDP) in acquired heart disease. The correlation between VEDP and PAWP and their
      performance as surrogates for LAP in Fontan patients is unknown. METHODS: Offline
      single-beat simultaneous measurement of PAWP and VEDP was performed in 50 adult
      Fontan patients and non-simultaneous hemodynamic data abstracted for calculation
      of pulmonary vascular resistance (PVR). For the evaluation of PAWP and VEDP as
      surrogates for LAP, 14 fenestrated adult Fontan patients were included. RESULTS:
      Mean age was 34.2+/-10years and 54% of patients were female. Tricuspid atresia
      and double inlet left ventricle were the most common congenital defects (44% and
      20%, respectively). Simultaneous mean VEDP was 10.8+/-4.6mmHg and mean PAWP was
      11+/-4.6mmHg; the PAWP-VEDP correlation was 0.91 (p<0.001). Using non
      simultaneous data, right-sided (mean difference 0.6WU.m2, 95% CI 0.2-1.0;
      p=0.005) and left-sided (mean difference 0.5WU.m2, 95% CI 0.1-0.9; p=0.02) PVRs
      were significantly higher when PAWP rather than VEDP was used. In fenestrated
      patients, LAP-right PAWP and LAP-left PAWP correlations were 0.97 and 0.95
      (p<0.0001 for both), respectively, whereas the correlation between LAP-VEDP was
      0.76 (p=0.007). CONCLUSIONS: PAWP and VEDP correlate reasonably well in adult
      Fontan patients but PAWP is a better surrogate for LAP. The use of VEDP instead
      of PAWP appears to significantly underestimate PVR in these patients.

PMID- 29338919
TI  - Agreement among Magnetic Resonance Imaging/Magnetic Resonance
      Cholangiopancreatography (MRI-MRCP) and Endoscopic Ultrasound (EUS) in the
      evaluation of morphological features of Branch Duct Intraductal Papillary
      Mucinous Neoplasm (BD-IPMN).
AB  - BACKGROUND/OBJECTIVES: To evaluate the agreement between the imaging modalities
      MRI-MRCP and EUS in cystic lesions of the pancreas which were thought to be a BD
      IPMN. METHODS: Multicenter retrospective study included all patients between 2010
      and 2015 with a suspected BD-IPMN who underwent an EUS and MRI-MRCP within 6
      months or less of each other. Location, number, size, worrisome features and high
      risk stigmata were evaluated. Interobserver agreement was evaluated by Kappa
      score. RESULTS: 173 patients were included (97 UHSC, 76 UCLH-RFH), mean age 65
      (range 25-87 years), 66 males. When comparing both modalities there was good
      agreement for the location of the cyst. The median lesion size was larger by MRI
      MRCP than EUS although it was not significant. With regards to worrisome
      features, there was moderate agreement for main PD of 5-9 mm and abrupt change (k
      = 0.45 and 0.52). Fair agreement was seen for the cyst wall thickening (k =
      0.25). No agreement was seen between the presence of non-enhanced mural nodules
      or lymphadenopathy (k < 0). With regards to high-risk stigmata, poor agreement
      was obtained for the detection of an enhanced solid component (k = 0.12). No
      agreement was observed for main PD > 10 mm (k < 0). CONCLUSIONS: In this
      multicentre study of patients with a BD-IPMN under active surveillance, most
      disagreement between these modalities was seen in the proximal pancreas. There
      was generally only minimal concordance between the imaging findings of EUS and
      MRI-MRCP for the detection of high-risk stigmata and worrisome features.

PMID- 29338920
TI  - Endoscopic ultrasound guided 22 gauge core needle biopsy for the diagnosis of
      Autoimmune pancreatitis.
AB  - BACKGROUND: It is difficult to obtain adequate tissue sample for diagnosing
      autoimmune pancreatitis (AIP) with the help of traditional EUS-guided FNA. As per
      ICDC guidelines, EUS-guided FNA is not recommended for diagnosing AIP(1). We
      herein present a report of 2 cases of using a new flexible 22 gauge (G) core
      biopsy needle (SharkCore, Medtronic, Sunnydale, Calif) for diagnosing AIP.
      METHODS: This is a report of 2 cases reviewed retrospectively which had used 22G
      core biopsy needle for obtaining histo-pathological samples for diagnosing AIP.
      The cases were reviewed with both endoscopist and a pathologist to determine if
      the diagnostic criteria were met. RESULTS: Both the cases had adequate tissue
      sample obtained to make a clear diagnosis of AIP. Pathology showed changes of
      chronic pancreatitis with atrophy and storiform pattern of fibrosis with a dense
      lymphoplasmacytic infiltrate in both cases along with identification of IgG4
      cells. CONCLUSION: EUS-guided fine needle biopsy (FNB) using the SharkCore needle
      can be used reliably for diagnosing AIP. More studies need to be performed to
      validate this further.

PMID- 29338921
TI  - Faster progression from MCI to probable AD for carriers of a single-nucleotide
      polymorphism associated with type 2 diabetes.
AB  - Sporadic Alzheimer's disease (AD), as opposed to its autosomal dominant form, is
      likely caused by a complex interaction of genetic, environmental, and health
      lifestyle factors. Twin studies indicate that sporadic AD heritability could be
      between 58% and 79%, around half of which is explained by the epsilon4 allele of
      the apolipoprotein E (APOE4). We hypothesized that genes associated with known
      risk factors for AD, namely hypertension, hypercholesterolemia, obesity,
      diabetes, and cardiovascular disease, would contribute significantly to the
      remaining heritability. We analyzed 22 AD-associated single-nucleotide
      polymorphisms (SNPs), associated with these risk factors, that were included in
      the sequencing data of the Alzheimer's Disease Neuroimaging Initiative 1 data
      set, which included 355 participants with mild cognitive impairment (MCI). We
      built survival models with the selected SNPs to predict progression of MCI to
      probable AD over the 10-year follow-up of the study. The rs391300 SNP, located on
      the serine racemase (SRR) gene and linked to increased susceptibility to type 2
      diabetes, was associated with progression from MCI to probable AD.

PMID- 29338922
TI  - Alcohol consumption, masculinity, and alcohol-related violence and anti-social
      behaviour in sportspeople.
AB  - OBJECTIVES: There is no research examining alcohol-related aggression and anti
      social behaviour in UK or European sportspeople (athletes), and no research has
      examined relationships between masculinity, alcohol consumption, and alcohol
      related aggression and antisocial behaviour in sportspeople (athletes). This
      study addresses this gap. DESIGN: Cross-sectional. METHODS: A sample (N=2048;
      women=892, 44%) of in season sportspeople enrolled at UK universities (response
      83%), completed measures of masculinity, alcohol consumption, within-sport (on
      field) violence, and having been the perpetrator and/or victim of alcohol-related
      violent/aggressive and antisocial behaviour (e.g., hit/assaulted, vandalism,
      sexual assault). Logistic regressions examined predictors of alcohol-related
      violence/aggression and anti-social behaviours. RESULTS: Significant bivariate
      relationships between masculinity, within-sport violence, alcohol consumption,
      and alcohol-related aggression and anti-social behaviour were found for both men
      and women (p's<.001). Logistic regression adjusting for all variables showed that
      higher levels of masculinity and alcohol consumption in men and women were
      related to an increased odds of having conducted an aggressive, violent and/or
      anti-social act in the past 12 months when intoxicated. Odds ratios were largest
      for relationships between masculinity, alcohol consumption, within-sport
      violence, and interpersonal violence/aggression (p's<.001). A similar pattern of
      results was found for having been the victim of aggression and anti-social
      behaviour. CONCLUSIONS: Alcohol-related aggression and anti-social behaviour
      appear to be problematic in UK university sportspeople, and is related to
      masculinity and excessive drinking. Interventions that reduce excessive alcohol
      consumption, masculine norms and associated within-sport violence, could be
      effective in reducing alcohol-related aggression and antisocial behaviour in UK
      sportspeople.

PMID- 29338924
TI  - Dynamic Epigenetic Changes during Plant Regeneration.
AB  - Plants have the remarkable ability to drive cellular dedifferentiation and
      regeneration. Changes in epigenetic landscapes accompany the cell fate
      transition. Notably, modifications of chromatin structure occur primarily during
      callus formation via an in vitro tissue culture process and, thus, pluripotent
      callus cells have unique epigenetic signatures. Here, we highlight the latest
      progress in epigenetic regulation of callus formation in plants, which addresses
      fundamental questions related to cell fate changes and pluripotency
      establishment. Global and local modifications of chromatin structure underlie
      callus formation, and the combination and sequence of epigenetic modifications
      further shape intricate cell fate changes. This review illustrates how a series
      of chromatin marks change dynamically during callus formation and their
      biological relevance in plant regeneration.

PMID- 29338923
TI  - Minimally invasive hysterectomy surgery rates for endometrial cancer performed at
      National Comprehensive Cancer Network (NCCN) Centers.
AB  - OBJECTIVES: Minimally invasive surgery (MIS) is a quality measure for endometrial
      cancer (EC) established by the Society of Gynecologic Oncology and the American
      College of Surgeons. Our study objective was to assess the proportion of EC cases
      performed by MIS at National Comprehensive Cancer Network (NCCN) centers and
      evaluate perioperative outcomes. METHODS: A retrospective cohort study of women
      who underwent surgical treatment for EC from 2013 to 2014 was conducted at four
      NCCN centers. Multivariable mixed logistic regression models analyzed factors
      associated with failure to perform MIS and perioperative complications. RESULTS:
      In total 1621 patients were evaluated; 86.5% underwent MIS (robotic-assisted
      72.5%, laparoscopic 20.9%, vaginal 6.6%). On multivariable analysis, factors
      associated with failure to undergo MIS were uterine size >12cm (Odds Ratio [OR]:
      0.17, 95% CI 0.03-0.9), stage III (OR: 0.16, 95% CI 0.05-0.49) and IV disease
      (OR: 0.07, 95% CI 0.02-0.22). For stage I/II disease, complications occurred in
      5.1% of MIS and 21.7% of laparotomy cases (p<0.01). Laparotomy was associated
      with increases in any complication (OR: 6.0, 95% CI 3.3-10.8), gastrointestinal
      (OR: 7.2, 95% CI 2.6-19.5), wound (OR: 3.7, 95% CI 1.5-9.2), respiratory (OR
      37.5, 95% CI 3.9-358.0), VTE (OR 10.5, 95% CI 1.3-82.8) and 30-day readmission
      (OR: 2.6, 95% CI 1.4-4.9) compared to MIS. CONCLUSIONS: At NCCN-designated
      centers, the MIS hysterectomy rate in EC is higher than the published national
      average, with low perioperative complications. Previously identified disparities
      of age, race, and BMI were not observed. A proposed MIS hysterectomy benchmark of
      >80% in EC care is feasible when performed at high volume centers.

PMID- 29338925
TI  - Rituximab therapy in rheumatoid arthritis and primary biliary cholangitis.

PMID- 29338926
TI  - Can you tell the difference: Round vs anatomical implants - A real-time global
      ballot.

PMID- 29338927
TI  - Brain injury due to head banging in Tourette.

PMID- 29338928
TI  - Immunoproteomic identification of antigenic candidate Campylobacter jejuni and
      human peripheral nerve proteins involved in Guillain-Barre syndrome.
AB  - Immunoproteomics is become a potent methodology used for identifying
      immunoreactive proteins. In this study, an immunoproteomic approach based on 2
      dimensional gel electrophoresis (2D-PAGE) and immunoblotting combined with high
      resolution mass spectrometry (MS) was used to identify immunoreactive proteins
      that might be involved in mechanisms of Guillain-Barre syndrome (GBS)
      development, regardless of their potential reciprocal molecular mimicry. Proteins
      isolated from C. jejuni and human peripheral nerve tissue (HPN) were separated
      with 2D SDS-PAGE and subjected to western blotting using serum samples from GBS
      patients. The peptides generated after proteolysis of the immunoreactive proteins
      were submitted to nanoflow-high performance liquid chromatography-nano
      electrospray ionization coupled to high resolution mass spectrometry (nHPLC-nESI
      MS and MS/MS) followed by SEQUESTdata analysis for proteins identification. In C.
      jejuni, immunoreactivity was found for GroEL and DnaK, structural proteins
      (MOMP), key enzymatic proteins necessary for the microbial proliferation
      (adenylate kinase, enolase, inorganic pyrophosphatase and aspartate ammonia
      lyase), and antioxidant enzymes (alkyl hydroperoxide reductase-AhpC and DNA
      protection during starvation protein - DNA protection factor against Fe2+
      mediated oxidative stress). HPN immunoreactive proteins identified were heat
      shock proteins (HSP), intermediate filaments (vimentin and desmin), and other
      proteins and enzymes such as troponin/tropomyosin complex and ATP synthase
      subunit beta and the keratan sulfate proteoglycan lumican. The targeting of
      vimentin and desmin, suggested that the neuronal autoimmune damage is
      specifically directed to intermediate neuronal (vimentin) and neuromuscular IF,
      probably localized nearby cell surface, affording increased accessibility to
      autoantibodies. These findings suggest that the post-infectious development of
      GBS may be also associated to additional concomitant immune factors that lead to
      nerve damage generated by auto-immune trigger(s) different from molecular
      mimicry.

PMID- 29338929
TI  - Differential anxiety-like behavior, HPA responsiveness, and host-resistance in
      mice with different circling preference.
AB  - Relationships between behavioral sidedness and immune responses in previous
      studies have differed depending on behavior tests and severity of biological
      stress in mice. It was necessary to elucidate the psychophysiological mediators
      that connect behavioral sidedness and immune responses. This study investigated
      interrelationships among anxiety-like behavior, the HPA axis responsiveness, and
      host-resistance to bacterial infection. Mice that preferred clockwise circling
      had lower locomotor activities, higher anxiety-like behavior, and faster
      activation of the HPA axis than mice that preferred counterclockwise circling. A
      fast activation of the HPA axis was associated with a higher host-resistance to
      low dose bacterial infection.

PMID- 29338930
TI  - Neurologic disorders associated with anti-glutamic acid decarboxylase antibodies:
      A comparison of anti-GAD antibody titers and time-dependent changes between
      neurologic disease and type I diabetes mellitus.
AB  - To determine clinical features of neurologic disorders associated with anti
      glutamic acid decarboxylase antibodies (anti-GAD-Ab), we examined titers and time
      dependent changes of anti-GAD-Ab. Six patients, stiff person syndrome (2),
      cerebellar ataxia (1), limbic encephalitis (1), epilepsy (1), brainstem
      encephalitis (1), were compared with 87 type I diabetes mellitus (T1DM) patients
      without neurologic disorders. Anti-GAD-Ab titers and index were higher in
      neurologic disorders than in T1DM, suggesting intrathecal antibody synthesis.
      Anti-GAD-Ab titers in T1DM decreased over time, whereas they remained high in
      neurologic disorders. Immunotherapy improved neurological disorders and anti-GAD
      Ab titers and index provide clinically meaningful information about their
      diagnostic accuracy.

PMID- 29338932
TI  - Functional characteristics of a renal H+/lipophilic cation antiport system in
      porcine LLC-PK1 cells and rats.
AB  - We have recently found an H+/quinidine (a lipophilic cation, QND) antiport system
      in Madin-Darby canine kidney (MDCK) cells. The primary aim of the present study
      was to evaluate whether the H+/lipophilic cation antiport system is expressed in
      porcine LLC-PK1 cells. That is, we investigated uptake and/or efflux of QND and
      another cation, bisoprolol, in LLC-PK1 cells. In addition, we studied the renal
      clearance of bisoprolol in rats. Uptake of QND into LLC-PK1 cells was decreased
      by acidification of the extracellular pH or alkalization of the intracellular pH.
      Cellular uptake of QND from the apical side was much greater than from the
      basolateral side. In addition, apical efflux of QND from LLC-PK1 cells was
      increased by acidification of the extracellular pH. Furthermore, lipophilic
      cationic drugs significantly reduced uptake of bisoprolol in LLC-PK1 cells. Renal
      clearance of bisoprolol in rats was approximately 7-fold higher than that of
      creatinine, and was markedly decreased by alkalization of the urine pH. The
      present study suggests that the H+/lipophilic cation antiport system is expressed
      in the apical membrane of LLC-PK1 cells. Moreover, the H+/lipophilic cation
      antiport system may be responsible for renal tubular secretion of bisoprolol in
      rats.

PMID- 29338931
TI  - In vitro activity of eravacycline against 2213 Gram-negative and 2424 Gram
      positive bacterial pathogens isolated in Canadian hospital laboratories: CANWARD
      surveillance study 2014-2015.
AB  - Gram-negative (n=2213) and Gram-positive (n=2424) pathogens isolated from
      patients in 13 Canadian hospitals in 2014 and 2015 were tested for in vitro
      susceptibility to eravacycline and comparators using the Clinical and Laboratory
      Standards Institute broth microdilution method. The concentration of eravacycline
      inhibiting 90% of isolates (MIC90) ranged from 0.5 to 2MUg/mL for 9 species of
      Enterobacteriaceae tested (n=2067). Eravacycline activity was largely unaffected
      by extended-spectrum beta-lactamase phenotypes in Escherichia coli (n=141) and
      Klebsiella pneumoniae (n=21). Eravacycline was active against Acinetobacter
      baumannii (n=28; MIC90, 0.5MUg/mL) and Stenotrophomonas maltophilia (n=118;
      MIC90, 4MUg/mL). Eravacycline MIC90 for staphylococci (n=1653), enterococci
      (n=289), and streptococci (n=482) ranged from 0.12 to 0.25, 0.06 to 0.12, and
      0.015 to 0.06MUg/mL, respectively. Eravacycline's potency was equivalent to or 2-
      to 4-fold greater than tigecycline against Enterobacteriaceae and Gram-positive
      cocci tested. Eravacycline demonstrates promising activity against recent
      clinical Gram-negative and Gram-positive bacteria, including multidrug-resistant
      pathogens.

PMID- 29338933
TI  - Physiological based pharmacokinetic modeling to estimate in vivo Ki of
      ketoconazole on renal P-gp using human drug-drug interaction study result of
      fesoterodine and ketoconazole.
AB  - This study was conducted to estimate in vivo inhibition constant (Ki) of
      ketoconazole on renal P-glycoprotein (P-gp) using human drug-drug interaction
      (DDI) study result of fesoterodine and ketoconazole. Fesoterodine is a prodrug
      which is extensively hydrolyzed by non-specific esterases to the active
      metabolite 5-hydroxymethyl tolterodine (5-HMT). 5-HMT is then further metabolized
      via Cytochrome P450 (CYP) 2D6 and CYP3A4. It is reported that 5-HMT is a
      substrate of P-gp whereas fesoterodine is not. Renal clearance of 5-HMT is
      approximately two-times greater than renal glomerular filtration rate. This
      suggests the possibility that renal clearance of 5-HMT involves secretion by P
      gp. Utilizing the available pharmacokinetic characteristics of fesoterodine and 5
      HMT, we estimated in vivo Ki of ketoconazole on P-gp at kidney based on DDI study
      data using physiologically-based pharmacokinetic approach. The estimated in vivo
      Ki of ketoconazole for hepatic CYP3A4 (6.64 ng/mL) was consistent with the
      reported values. The in vivo Ki of ketoconazole for renal P-gp was successfully
      estimated as 2.27 ng/mL, which was notably lower than reported in vitro 50%
      inhibitory concentration (IC50) values ranged 223-2440 ng/mL due to different
      condition between in vitro and in vivo.

PMID- 29338934
TI  - Systematic review of the safety and effectiveness of peripheral neurostimulation
      of the sphenopalatine ganglion for the treatment of refractory chronic cluster
      headache.
AB  - INTRODUCTION: This study aimed to assess the safety and effectiveness of
      peripheral neurostimulation of the sphenopalatine ganglion (SPG) in the treatment
      of refractory chronic cluster headache. DEVELOPMENT: Various medical databases
      were used to perform a systematic review of the scientific literature. The search
      for articles continued until 31 October 2016, and included clinical trials,
      systematic reviews and/or meta-analyses, health technology assessment reports,
      and clinical practice guidelines that included measurements of
      efficiency/effectiveness or adverse effects associated with the treatment. The
      review excluded cohort studies, case-control studies, case series, literature
      reviews, letters to the editor, opinion pieces, editorials, and studies that had
      been duplicated or outdated by later publications from the same institution.
      Regarding effectiveness, we found that SPG stimulation had positive results for
      pain relief, attack frequency, medication use, and patients' quality of life. In
      the results regarding safety, we found a significant number of adverse events in
      the first 30 days following the intervention. Removal of the device was necessary
      in some patients. Little follow-up data, and no long-term data, is available.
      CONCLUSIONS: These results are promising, despite the limited evidence available.
      We consider it essential for research to continue into the safety and efficacy of
      SPG stimulation for patients with refractory chronic cluster headache. In cases
      where this intervention may be indicated, treatment should be closely monitored.

PMID- 29338935
TI  - Compassionate use of human recombinant insulin-like growth factor-1 therapy in
      Friedreich's ataxia.

PMID- 29338936
TI  - Continuous intestinal infusion of levodopa-carbidopa in patients with advanced
      Parkinson's disease in Spain: Subanalysis by autonomous community.
AB  - OBJECTIVES: To compare the characteristics of patients undergoing treatment with
      continuous intestinal infusion of levodopa-carbidopa (CIILC) for advanced
      Parkinson's disease and the data on the effectiveness and safety of CIILC in the
      different autonomous communities (AC) of Spain. METHODS: A retrospective,
      longitudinal, observational study was carried out into 177 patients from 11 CAs
      who underwent CIILC between January 2006 and December 2011. We analysed data on
      patients' clinical and demographic characteristics, variables related to
      effectiveness (changes in off time/on time with or without disabling dyskinesia;
      changes in Hoehn and Yahr scale and Unified Parkinson's Disease Rating Scale
      scores; non-motor symptoms; and Clinical Global Impression scale scores) and
      safety (adverse events), and the rate of CIILC discontinuation. RESULTS:
      Significant differences were observed between CAs for several baseline variables:
      duration of disease progression prior to CIILC onset, off time (34.9-59.7%) and
      on time (2.6-48.0%; with or without disabling dyskinesia), Hoehn and Yahr score
      during on time, Unified Parkinson's Disease Rating Scale-III score during both on
      and off time, presence of>= 4 motor symptoms, and CIILC dose. Significant
      differences were observed during follow-up (> 24 months in 9 of the 11 CAs
      studied) for the percentage of off time and on time without disabling dyskinesia,
      adverse events frequency, and Clinical Global Impression scores. The rate of
      CIILC discontinuation was between 20-40% in 9 CAs (78 and 80% in remaining 2
      CAs). CONCLUSIONS: This study reveals a marked variability between CAs in terms
      of patient selection and CIILC safety and effectiveness. These results may have
      been influenced by patients' baseline characteristics, the availability of
      multidisciplinary teams, and clinical experience.

PMID- 29338937
TI  - Neuroimaging in hypoglycaemic encephalopathy diagnosis and prognosis: A case
      report.

PMID- 29338938
TI  - Distinct MET Protein Localization Associated With MET Exon 14 Mutation Types in
      Patients With Non-small-cell Lung Cancer.
AB  - BACKGROUND: The MET gene has been recognized as a potential important therapeutic
      target in non-small-cell lung cancer (NSCLC). We sought to investigate the MET
      exon 14 mutations in a cohort of Chinese patients with NSCLC. METHODS: We tested
      461 NSCLCs for MET exon 14 mutations by sequencing whole exon 14 and its flanking
      introns. The protein expression was determined by immunohistochemical analysis.
      RESULTS: In this study, we identified MET exon 14 mutations in 9 (2.0%) of 461
      NSCLCs. Of these 9 mutations, 7 (77.8%) were located in the splice sites of MET
      exon 14, with MET overexpression in 6. One point mutation c.3010C>T
      (p.Arg1004Ter) was nonsense mutation with no MET expression. One insertion
      mutation was within exon 14 of MET with MET overexpression. MET protein
      localization in tumor cells with MET exon 14 mutations was different between
      mutation types. Three point mutations that disrupted the splice donor site of
      intron 14 were membranous staining, whereas the other mutations were cytoplasmic
      staining. Patients with MET exon 14 splice site mutations were significantly
      older. The incidence of MET exon 14 mutations in sarcomatoid carcinoma was
      significantly higher than in other histologic types (P = .034). CONCLUSION:
      Distinct MET protein localization is associated with MET exon 14 mutation types
      in patients with NSCLC. Different MET exon 14 mutation types were identified in a
      subset of Chinese patients with NSCLC who could possibly benefit from MET
      targeted therapy.

PMID- 29338939
TI  - Immune Cytokines and Their Receptors in Inflammatory Pain.
AB  - There is burgeoning interest in the interaction between the immune and nervous
      systems. Pain is mediated by primary sensory neurons (nociceptors) that can
      respond to a variety of thermal, mechanical and chemical signals. Cytokines are
      now recognized as important mediators of inflammatory pain. They can induce
      nociceptor sensitization indirectly via mediators, wherein neurons become primed
      and thus become more responsive to stimulation; alternatively, there is also
      evidence that cytokines can directly activate neurons via their specific
      receptors present on the neuronal cells. We review here the evidence for and
      against these respective mechanisms, focusing on arthritis and inflammatory skin
      models. A number of striking inconsistencies amongst the conclusions made in the
      literature are highlighted and discussed.

PMID- 29338940
TI  - Chimney Stent Technique in a Valve-in-valve Procedure.

PMID- 29338941
TI  - Epiglottoplasty technique in endoscopic partial laryngectomy.
AB  - The main advantage of endoscopic laser surgery for laryngeal cancer is to allow
      tumour resection, while limiting functional sequelae, thereby improving the
      postoperative course. In this type of surgery, the epiglottis is often partially
      resected, leaving a raw zone without any reconstruction. The surgical technique
      described here involves endoscopic reconstruction of the epiglottis after partial
      resection. The sectioned edge of the epiglottis is sutured to the base of the
      tongue to create a neoepiglottis and to reconstruct the vallecula, thus
      resembling preoperative anatomy, allowing improvement of postoperative
      swallowing.

PMID- 29338942
TI  - International consensus (ICON) on treatment of Meniere's disease.
AB  - OBJECTIVE: To present the international consensus for recommendations for
      Meniere's disease (MD) treatment. METHODS: Based on a literature review and
      report of 4 experts from 4 continents, the recommendations have been presented
      during the 21st IFOS congress in Paris, in June 2017 and are presented in this
      work. RESULTS: The recommendation is to change the lifestyle, to use the
      vestibular rehabilitation in the intercritic period and to propose psychotherapy.
      As a conservative medical treatment of first line, the authors recommend to use
      diuretics and Betahistine or local pressure therapy. When medical treatment
      fails, the recommendation is to use a second line treatment, which consists in
      the intratympanic injection of steroids. Then as a third line treatment,
      depending on the hearing function, could be either the endolymphatic sac surgery
      (when hearing is worth being preserved) or the intratympanic injection of
      gentamicin (with higher risks of hearing loss). The very last option is the
      destructive surgical treatment labyrinthectomy, associated or not to cochlear
      implantation or vestibular nerve section (when hearing is worth being preserved),
      which is the most frequent option.

PMID- 29338943
TI  - Physiology of the paransal sinus ostia: Endoscopic findings.

PMID- 29338944
TI  - Histological and morphofunctional parameters of the hypothalamic-pituitary
      adrenal system are sensitive to daidzein treatment in the adult rat.
AB  - The isoflavone, daidzein is a biologically active, plant-derived compound that
      interacts with estrogen receptors. Data from previous studies have suggested that
      daidzein exerts beneficial effects in many diseases; however, as an endocrine
      disrupter, it may also alter the functioning of the endocrine system. Data
      regarding the effect of daidzein on the morphofunctional and histological
      parameters of the hypothalamic-pituitary-adrenal (HPA) system is still lacking.
      Therefore, using the newCAST stereological software, we investigated the effects
      of chronic (21 days) daidzein treatment on corticotropin-releasing hormone (CRH)
      neurons within the hypothalamus and corticotropes (ACTH cells) in the pituitary,
      while image analysis was employed to-examine the intensity of fluorescence of CRH
      in the median eminence (ME) and adrenocorticotropin hormone in the pituitary in
      adult orchidectomized (Ovx) rats. Circulating ACTH and corticosterone levels were
      also analyzed. This study showed that daidzein treatment decreased the volume
      density of CRH neurons within the paraventricular nucleus as well as CRH
      immunofluorescence in the ME. The total number of ACTH cells was decreased, while
      ACTH cell volume and the intensity of ACTH fluorescence were increased following
      daidzein treatment. Both ACTH and corticosterone blood levels were increased
      after daidzein administration. The results of performed experiments clearly
      demonstrate that volume density of CRH neurons; total number and volume of ACTH
      cells, as well as stress hormones levels are vulnerable to the effects of
      daidzein.

PMID- 29338945
TI  - Editorial Comment.

PMID- 29338946
TI  - Reply.

PMID- 29338947
TI  - Reply.

PMID- 29338948
TI  - Editorial Comment.

PMID- 29338949
TI  - Relation between cadmium exposure and gestational diabetes mellitus.
AB  - BACKGROUND: Cadmium (Cd) has been associated with type 2 diabetes in general
      population. However, the role of Cd in the occurrence of Gestational diabetes
      mellitus (GDM) remains unclear. OBJECTIVES: Our study was aimed at investigating
      whether Cd exposure during pregnancy was associated with increased risk of GDM.
      METHODS: Cd concentrations were measured in urine samples from 6837 pregnant
      women in Wuhan, China, from 2012 to 2014. A "modified Poisson" model with a
      robust error variance was used to examine the association of GDM with continuous
      natural logarithm (ln) transformed urinary Cd or quartiles of urinary Cd levels.
      RESULTS: For about 3-fold increase in Cd concentrations, there were 16% [relative
      risk (RR) =1.16; 95% confidence interval (CI): 1.03, 1.33] increase in risk of
      GDM. Compared with women in the lowest quartile of urinary Cd levels, women in
      the highest quartile had 1.30 higher risk of GDM [95% CI: 1.05, 1.61; p-trend
      <0.05]. Further analyses indicated overweight/obese women with higher urinary Cd
      levels had significantly higher risk of GDM, compared with women in the reference
      category of lowest quartile of Cd and normal pre-pregnancy body mass index [RR
      =2.71; 95% CI: 1.81, 4.07]. CONCLUSIONS: Our study presented a significantly
      positive association between urinary Cd levels and risk of GDM, supporting the
      hypothesis that environmental exposure to Cd may contribute to the development of
      GDM.

PMID- 29338950
TI  - Sugar-Sweetened Beverage and Water Intake in Relation to Diet Quality in U.S.
      Children.
AB  - INTRODUCTION: Sugar-sweetened beverages (SSBs) are a major contributor to
      children's added sugar consumption. This study examines whether children's SSB
      and water intakes are associated with diet quality and total energy intake.
      METHODS: Using data on children aged 2-18 years from the 2009-2014 National
      Health and Nutrition Examination Survey, linear regression models were used to
      analyze SSB and water intake in relation to Healthy Eating Index 2010 (HEI-2010)
      scores and total energy intake. Generalized linear models were used to analyze
      SSB and water intake in relation to the HEI-2010 scores. Analyses were conducted
      including and excluding caloric contributions from SSBs and were conducted in
      2016-2017. RESULTS: SSB intake was inversely associated with the HEI-2010 total
      scores (9.5-point lower score comparing more than two servings/day with zero
      servings/day, p-trend<0.0001) and positively associated with total energy intake
      (394 kcal higher comparing more than two servings/day with zero servings/day, p
      trend<0.0001). The associations between SSB and HEI-2010 total scores were
      similar when SSBs were excluded from HEI-2010 calculations. Water intake was
      positively associated with HEI-2010 total scores, but not associated with total
      energy intake. SSB intake was inversely associated with several HEI-2010
      component scores, notably vegetables, total fruit, whole fruit, greens and beans,
      whole grains, dairy, seafood and plant proteins, and empty calories. Water intake
      was positively associated with most of the same HEI-2010 component scores.
      CONCLUSIONS: Children who consume SSBs have poorer diet quality and higher total
      energy intake than children who do not consume SSBs. Interventions for obesity
      and chronic disease should focus on replacing SSBs with water and improving other
      aspects of diet quality that correlate with SSB consumption.

PMID- 29338951
TI  - Small Incentives Improve Weight Loss in Women From Disadvantaged Backgrounds.
AB  - INTRODUCTION: Women from lower-income backgrounds have the highest rates of
      obesity. Thus, effective programs for this high-risk population are urgently
      needed. Evidence suggests that adding financial incentives to treatment helps to
      engage and promote health behavior change in lower-income populations; however,
      this has never been tested in women for obesity treatment. The purpose of this
      study was to examine whether adding small financial incentives to Internet weight
      loss treatment yields better weight loss outcomes in women from lower-income
      backgrounds compared with the same treatment without incentives. Weight losses in
      lower-versus higher-income women were also compared. METHODS: Data were pooled
      from two randomized trials in which women (N=264) received either Internet
      behavioral weight loss treatment (IBWL) or IBWL plus incentives (IBWL+$). Weight
      was objectively assessed. Data were collected and analyzed from 2011 to 2017.
      RESULTS: Women from lower-income backgrounds had significantly better weight loss
      outcomes in IBWL+$ compared with IBWL alone (6.4 [SD=4.9%] vs 2.6 [SD=4.6%],
      p=0.01). Moreover, a greater percentage achieved a >=5% weight loss in IBWL+$ vs
      IBWL alone (52.6% vs 38.1%, p=0.01). Interestingly, the comparison between lower
      income versus higher-income groups showed that, in IBWL alone, women with lower
      income achieved significantly poorer weight losses (3.4 [SD=4.2%] vs 4.9
      [SD=4.0%], p=0.03). By contrast, in IBWL+$, weight loss outcomes did not differ
      by income status (5.0 [SD=5.6%] vs 5.3 [SD=3.8%], p=0.80), and a similar
      percentage of lower- versus higher-income women achieved a >=5% weight loss
      (52.6% vs 53.8%, p=0.93). CONCLUSIONS: An Internet behavioral weight loss program
      plus financial incentives may be an effective strategy to promote excellent
      weight losses in women with lower income, thereby enhancing equity in treatment
      outcomes in a vulnerable, high-risk population. These data also provide important
      evidence to support federally funded incentive initiatives for lower-income,
      underserved populations.

PMID- 29338952
TI  - Behavioral Risk Factors and Regional Variation in Cardiovascular Health Care and
      Death.
AB  - INTRODUCTION: Reducing the burden of death from cardiovascular disease includes
      risk factor reduction and medical interventions. METHODS: This was an
      observational analysis at the hospital service area (HSA) level, to examine
      regional variation and relationships between behavioral risks, health services
      utilization, and cardiovascular disease mortality (the outcome of interest). HSA
      level prevalence of cardiovascular disease behavioral risks (smoking, poor diet,
      physical inactivity) were calculated from the Behavioral Risk Factor Surveillance
      System; HSA-level rates of stress tests, diagnostic cardiac catheterization, and
      revascularization from a statewide multi-payer claims data set from Maine in 2013
      (with 606,260 patients aged >=35 years), and deaths from state death certificate
      data. Analyses were done in 2016. RESULTS: There were marked differences across
      32 Maine HSAs in behavioral risks: smoking (12.4%-28.6%); poor diet (43.6%
      73.0%); and physical inactivity (16.4%-37.9%). After adjustment for behavioral
      risks, rates of utilization varied by HSA: stress tests (28.2-62.4 per 1,000
      person-years, coefficient of variation=17.5); diagnostic cardiac catheterization
      (10.0-19.8 per 1,000 person-years, coefficient of variation=17.3); and
      revascularization (4.6-6.2 per 1,000 person-years; coefficient of variation=9.1).
      Strong HSA-level associations between behavioral risk factors and cardiovascular
      disease mortality were observed: smoking (R2=0.52); poor diet (R2=0.38); and
      physical inactivity (R2=0.35), and no association between revascularization and
      cardiovascular disease mortality after adjustment for behavioral risk factors
      (R2=0.02). HSA-level behavioral risk factors were also strongly associated with
      all-cause mortality: smoking (R2=0.57); poor diet (R2=0.49); and physical
      inactivity (R2=0.46). CONCLUSIONS: There is substantial regional variation in
      behavioral risks and cardiac utilization. Behavioral risk factors are associated
      with cardiovascular disease mortality regionally, whereas revascularization is
      not. Efforts to reduce cardiovascular disease mortality in populations should
      focus on prevention efforts targeting modifiable risk factors.

PMID- 29338953
TI  - Violent Crime and Park Use in Low-Income Urban Neighborhoods.
AB  - INTRODUCTION: Crime and safety are often cited as potential hurdles to park use
      and park-based physical activity. Using comprehensive data sources including both
      objective and subjective measurements at the park level and the individual level,
      this study aimed to assess the association between crime rates and use of local
      parks in low-income urban neighborhoods. METHODS: The authors observed 48 parks
      and conducted local resident surveys in low-income neighborhoods in Los Angeles
      during a 2-year study period (2013-2015). Crime data were geocoded within a 1
      mile radius of parks' addresses and longitudinal models were fitted to estimate
      the association between crime rates and park use outcomes in 2017. RESULTS: One
      gun-related violent crime per 10,000 people during the 6-month period prior to
      data collection was associated with an average of 13.5%-15.8% reduction in
      observed park use and park-based moderate to vigorous physical activity (p<0.05)
      in the 6-month observation period. The relationship was significant in seniors
      (33%-40% reduction) and adults (13%-18%), but insignificant for teenagers (2%-4%)
      and children (10%-12%). Homicide rates were also significantly related to lower
      self-reported park use (p<0.05). CONCLUSIONS: Gun-related violent crimes have
      relatively long-term negative associations with population health by reducing
      utilization of outdoor park space. There can be additional population health
      benefits from controlling and reducing gun-related violent crimes beyond
      immediate impacts on public safety and mortality.

PMID- 29338954
TI  - Perceived and Observed Food Environments, Eating Behaviors, and BMI.
AB  - INTRODUCTION: This study examines relationships between perceived and observed
      nutrition environments, diet, and BMI, in order to examine the criterion validity
      of the Nutrition Environment Measures Survey-Perceived (NEMS-P). METHODS: In a
      cross-sectional study, perceived nutrition environments were assessed (NEMS-P)
      among 221 adults from four neighborhoods in the Philadelphia area in 2010 and
      2011. A total of 158 food store environments were observed using the NEMS-Stores.
      Data analyses were conducted in 2016. Bivariate Spearman rank correlations were
      used to examine relationships between perceived and observed availability,
      quality, and price of fruits and vegetables in respondents' neighborhoods. Linear
      regression models were used to examine relationships between perceived
      neighborhood and home food environments and daily fruit and vegetable consumption
      and BMI. RESULTS: A significant, positive relationship was found between
      perceived and observed availability of fruits and vegetables in the neighborhood
      (r = 0.36, p<0.001). A similar relationship was seen between perceived and
      observed quality of fruits and vegetables (r = 0.34, p<0.001). Perceived
      availability and quality of fruits and vegetables in the neighborhood, and
      availability and accessibility of fruits and vegetables in the home, were
      significantly related to daily fruit and vegetable consumption. Perceived price
      of food in the neighborhood was significantly associated with BMI. CONCLUSIONS:
      Responses to a self-reported survey to assess perceived food environments related
      to fruits and vegetables were significantly associated with observed nutrition
      environments, fruit and vegetable consumption, and BMI. The perceived prices of
      fruits and vegetables were modestly associated with BMI and warrant further
      testing in prospective studies. When observations of food environments are not
      feasible, residents' survey responses are an acceptable indicator, with
      reasonable criterion validity.

PMID- 29338955
TI  - Declining Health-Related Quality of Life in the U.S.
AB  - INTRODUCTION: Despite recent declining mortality of the U.S. population from most
      leading causes, uncertainty exists over trends in health-related quality of life.
      METHODS: The 2001-2002 and 2012-2013 National Epidemiologic Surveys on Alcohol
      and Related Conditions U.S. representative household surveys were analyzed for
      trends in health-related quality of life (n=79,402). Health-related quality of
      life was measured with the Short Form-6 Dimension scale derived from the Short
      Form-12. Changes in mean Short Form-6 Dimension ratings were attributed to
      changes in economic, social, substance abuse, mental, and medical risk factors.
      RESULTS: Mean Short Form-6 Dimension ratings decreased from 0.820 (2001-2002) to
      0.790 (2012-2013; p<0.0001). In regressions adjusted for age, sex,
      race/ethnicity, and education, variable proportions of this decline were
      attributable to medical (21.9%; obesity, cardiac disease, hypertension,
      arthritis, medical injury), economic (15.6%; financial crisis, job loss),
      substance use (15.3%; substance use disorder or marijuana use), mental health
      (13.1%; depression and anxiety disorders), and social (11.2%; partner, neighbor,
      or coworker problems) risks. In corresponding adjusted models, a larger
      percentage of the decline in Short Form-6 Dimension ratings of older adults (aged
      >=55 years) was attributable to medical (35.3%) than substance use (7.4%) risk
      factors, whereas the reverse occurred for younger adults (aged 18-24 years; 5.7%
      and 19.7%) and adults aged 25-44 years (12.7% and 16.3%). CONCLUSIONS: Between
      2001-2002 and 2012-2013, there was a significant decline in average quality of
      life ratings of U.S. adults. The decline was partially attributed to increases in
      several modifiable risk factors, with medical disorders having a larger role than
      substance use disorders for older adults but the reverse for younger and middle
      aged adults.

PMID- 29338956
TI  - Gender Identity Disparities in Cancer Screening Behaviors.
AB  - INTRODUCTION: Transgender (trans) and gender-nonconforming adults have reported
      reduced access to health care because of discrimination and lack of knowledgeable
      care. This study aimed to contribute to the nascent cancer prevention literature
      among trans and gender-nonconforming individuals by ascertaining rates of breast,
      cervical, prostate, and colorectal cancer screening behaviors by gender identity.
      METHODS: Publicly available de-identified data from the 2014-2016 Behavioral Risk
      Factor Surveillance System surveys were utilized to evaluate rates of cancer
      screenings by gender identity, while controlling for healthcare access,
      sociodemographics, and survey year. Analyses were conducted in 2017. RESULTS:
      Weighted chi-square tests identified significant differences in the proportion of
      cancer screening behaviors by gender identity among lifetime colorectal cancer
      screenings, Pap tests, prostate-specific antigen tests, discussing prostate
      specific antigen test advantages/disadvantages with their healthcare provider,
      and up-to-date colorectal cancer screenings and Pap tests (p<0.036). Weighted
      logistic regressions found that although some differences based on gender
      identity were fully explained by covariates, trans women had reduced odds of
      having up-to-date colorectal cancer screenings compared to cisgender (cis) men
      (AOR=0.20) and cis women (AOR=0.24), whereas trans men were more likely to ever
      receive a sigmoidoscopy/colonoscopy as compared to cis men (AOR=2.76) and cis
      women (AOR=2.65). Trans women were more likely than cis men to have up-to-date
      prostate-specific antigen tests (AOR=3.19). Finally, trans men and gender
      nonconforming individuals had reduced odds of lifetime Pap tests versus cis women
      (AOR=0.14 and 0.08, respectively), and gender-nonconforming individuals had lower
      odds of discussing prostate-specific antigen tests than cis men (AOR=0.09; all
      p<0.05). CONCLUSIONS: The findings indicate that gender identity disparities in
      cancer screenings persist beyond known sociodemographic and healthcare factors.
      It is critical that gender identity questions are included in cancer and other
      health-related surveillance systems to create knowledge to better inform
      healthcare practitioners and policymakers of appropriate screenings for trans and
      gender-nonconforming individuals.

PMID- 29338957
TI  - Commuting and Sleep: Results From the Hispanic Community Health Study/Study of
      Latinos Sueno Ancillary Study.
AB  - INTRODUCTION: Commute time is associated with reduced sleep time, but previous
      studies have relied on self-reported sleep assessment. The present study
      investigated the relationships between commute time for employment and objective
      sleep patterns among non-shift working U.S. Hispanic/Latino adults. METHODS: From
      2010 to 2013, Hispanic/Latino employed, non-shift-working adults (n=760, aged 18
      64 years) from the Sueno study, ancillary to the Hispanic Community Health
      Study/Study of Latinos, reported their total daily commute time to and from work,
      completed questionnaires on sleep and other health behaviors, and wore wrist
      actigraphs to record sleep duration, continuity, and variability for 1 week.
      Survey linear regression models of the actigraphic and self-reported sleep
      measures regressed on categorized commute time (short: 1-44 minutes; moderate: 45
      89 minutes; long: >=90 minutes) were built adjusting for relevant covariates. For
      associations that suggested a linear relationship, continuous commute time was
      modeled as the exposure. Moderation effects by age, sex, income, and depressive
      symptoms also were explored. RESULTS: Commute time was linearly related to sleep
      duration on work days such that each additional hour of commute time conferred 15
      minutes of sleep loss (p=0.01). Compared with short commutes, individuals with
      moderate commutes had greater sleep duration variability (p=0.04) and lower
      interdaily stability (p=0.046, a measure of sleep/wake schedule regularity). No
      significant associations were detected for self-reported sleep measures.
      CONCLUSIONS: Commute time is significantly associated with actigraphy-measured
      sleep duration and regularity among Hispanic/Latino adults. Interventions to
      shorten commute times should be evaluated to help improve sleep habits in this
      minority population.

PMID- 29338958
TI  - Recommendations of the Second Panel on Cost Effectiveness in Health and Medicine:
      A Reference, Not a Rule Book.

PMID- 29338959
TI  - A new window into psychosis: The rise digital phenotyping, smartphone assessment,
      and mobile monitoring.
AB  - This commentary piece discusses recent advances in the use of mobile technologies
      like smartphone and wearable sensors for schizophrenia research. By framing both
      the opportunities as well as challenges for the field, this piece aims to frame
      the both current and future research efforts.

PMID- 29338960
TI  - Small-airway dysfunction precedes the development of asthma in children with
      allergic rhinitis.
AB  - BACKGROUND: Epidemiological evidence suggests the existence of a direct link
      between allergic rhinitis (AR) and asthma. Several studies also support the
      presence of small-airway dysfunction (SAD) in non-asthmatic children with AR.
      However, it remains unknown whether SAD can predict the progression of AR to
      asthma. Our objective was to explore the existence of SAD in non-asthmatic
      children with AR and to assessed its ability to predict the development of
      asthma. METHODS: Seventy-three 6-year-old children with intermittent moderate
      severe AR but without asthma symptoms/medication within the last two years,
      underwent spirometry and measurement of respiratory resistance (Rrs) and
      reactance (Xrs) before and after bronchodilation (BD) (300mcg salbutamol). Lung
      function measurements were performed in the absence of nasal symptoms and
      repeated at AR exacerbation. SAD was defined as >30% decrease in Rrs or >50%
      increase in Xrs at 6 or 8Hz post-BD. Participants were followed for five years.
      RESULTS: Twenty-three children (31.5%) developed asthma; this group presented
      significant post-BD changes in Rrs and Xrs, but only at AR exacerbation. The
      ability of these changes to predict the development of asthma was exceptional and
      superior to that of the spirometric parameters. SAD (22 children, 30.1%), emerged
      as the single most efficient predictor of asthma, independently of other risk
      factors such as parental asthma, personal history of eczema and type of allergic
      sensitisation. CONCLUSION: SAD precedes the development of asthma in children
      with AR. Changes in respiratory impedance at AR exacerbation may assist in
      identifying those at risk to progress to asthma.

PMID- 29338961
TI  - Is eosinophilic esophagitis an equivalent of pollen allergic asthma? Analysis of
      biopsies and therapy guided by component resolved diagnosis.
AB  - BACKGROUND: Eosinophilic esophagitis (EoE) is characterized by esophageal
      dysfunction and, histologically, by eosinophilic inflammation. There is not a
      clear etiologic treatment. Biopsies analysis using plant histology methods may
      show callose and pollen tubes in the esophageal mucosa. Component-resolved
      diagnosis (CRD) with microarrays could detect possible allergens involved and
      indicate an elimination diet and allergen immunotherapy (AIT). METHODS: One
      hundred and twenty-nine patients with EoE were tested for environmental and food
      allergens. CRD, histological and botanical analysis were performed. Clinical
      scores and endoscopic biopsy were performed every six months for three years.
      Fifty healthy patients, 50 asthmatics due to pollen, and 53 celiac disease
      patients were included as comparison groups. CRD-directed AIT was administered in
      91 EoE patients and elimination diet in 140 patients (87 EoE and all 53 CD
      patients). RESULTS: CRD detected allergen hypersensitivity in 87.6% of patients
      with EoE. The predominant allergens were grass group 1 (55%), lipid transfer
      proteins (LTP) of peach and mugwort, hazelnuts and walnuts. Callose from pollen
      tubes was found in 65.6% of biopsies. After CRD-guided elimination diet and/or
      AIT, 101 (78.3%) EoE patients showed significant clinical improvement (p<0.017)
      and 97 (75.2%) were discharged (negative biopsy, no symptoms, no medication)
      without relapse. AIT-treated patients had better outcomes (odds ratio 177.3, 95%
      CI 16.2-1939.0). CONCLUSION: CRD-directed AIT and/or elimination diet was
      efficient in treating EoE patients and was well tolerated.

PMID- 29338962
TI  - Knowledge on asthma, food allergies, and anaphylaxis: Assessment of elementary
      school teachers, parents/caregivers of asthmatic children, and university
      students in Uruguaiana, in the state of Rio Grande do Sul, Brazil.
AB  - INTRODUCTION: Allergic diseases have become an increasingly common reality in the
      last years, extending beyond the family context. OBJECTIVE: Assessing the level
      of knowledge on asthma, food allergies and anaphylaxis of asthmatic children's
      parents/caregivers (PC), elementary school teachers (EST) and university students
      (US) in Uruguaiana, RS, Brazil. METHOD: 577 individuals (PC - N=111; EST - N=177;
      US - N=299) took part in the study, answering the Newcastle Asthma Knowledge
      Questionnaire (validated for Portuguese) and another questionnaire on Food
      Allergy (FA) and anaphylaxis. RESULTS: Although PC have asthmatic children, their
      asthma knowledge level was average, slightly above that of EST and EU. The lack
      of knowledge on passive smoking, use of medications and their side effects should
      be highlighted. US have shown to be better informed about FA and anaphylaxis.
      However, even though a significant proportion of respondents know the most common
      symptoms of FA and anaphylaxis, few named subcutaneous adrenaline as the drug of
      choice for treating anaphylaxis. Although a significant number of respondents
      know about the possibility of anaphylactic reactions happening at school or in
      activities outside the school, we were surprised by the absence of conditions in
      schools to provide emergency care to such students. CONCLUSION: Despite the high
      prevalence of allergic diseases in childhood, asthmatic children's
      parents/caregivers, elementary school teachers and university students have
      inadequate levels of knowledge to monitor these patients.

PMID- 29338963
TI  - Loss of tolerance for fishes previously tolerated in children with fish food
      protein induced enterocolitis syndrome.
AB  - We describe two case reports presenting some novel information on fish FPIES.
      Fish FPIES to one fish does not always start at the same time to other fish.
      Additionally, development of tolerance to the index fish do not necessarily imply
      tolerance to other reactive fish. This reflects on the best management of
      children with FPIES fish.

PMID- 29338964
TI  - Validation of the Children's Sleep Habits Questionnaire in a sample of Greek
      children with allergic rhinitis.
AB  - BACKGROUND: Obstructive respiratory disorders, such as allergic rhinitis and
      asthma may impair sleep quality. The aim of this study is to validate the
      Children's Sleep Habits Questionnaire (CSHQ) for Greek children from 6 to 14
      years of age. No validated tool has been developed so far to assess sleep
      disturbances in Greek school-aged children. METHODS: We examined the reliability
      and validity of the CSHQ in a sample of children with allergic rhinitis (AR) and
      a non-clinical population of parents of these children as a proxy measure of
      children's AR quality of life (QoL) as evaluated by the Pediatric Allergic
      Rhinitis Quality of Life (PedARQoL) questionnaire. RESULTS: The CSHQ
      questionnaire Child's Form (CF) had a moderate internal consistency with a
      Cronbach's alpha 0.671 and Guttman split-half coefficient of 0.563 when
      correlated with the PedARQoL (CF). There was also a moderate intraclass
      correlation of ICC=0.505 between the responses to both questionnaires in the two
      visits. The CSHQ Parent's Form (PF) had a very good internal consistency with a
      Cronbach's alpha of 0.928 and Guttman split-half coefficient of 0.798. There was
      a high intraclass correlation of 0.643 between the responses in the two visits.
      CONCLUSIONS: The Greek version of the CSHQ CF, but particularly the PF has proved
      to be a very reliable clinical instrument, which can be used in clinical trials
      for assessing sleep quality in school-aged children with sleep disturbances
      because of obstructive airway disorders, such as AR.

PMID- 29338965
TI  - Quality of life and clinical characterization of patients with vernal
      keratoconjunctivitis in a pediatric population in Colombia.
AB  - : Vernal keratoconjunctivitis is one of the most serious ocular allergies that
      have the potential to induce large ocular morbidity and significant visual
      changes affecting the quality of life of these individuals. METHODOLOGY: This
      study was conducted in two phases. The first phase consisted of the clinical
      characterization of 32 patients from the Clinical Allergology center of the
      I.P.S. Universitaria from July 2014 to February 2015. A retrospective analysis of
      medical records was performed. In the second phase, the evaluation of quality of
      life was conducted using the questionnaire KIDSCREEN 27, which was validated in
      our population and evaluated as recommended by the creators of this instrument.
      RESULTS: A total of 24 patients (75%) were men, mean age of 12.1 (SD 2.6) years.
      100% of the patients had clinical evaluation and were monitored by Allergology
      and Ophthalmology, 12 patients (37.5%) were found in mild level, 5 patients
      (15.6%) were moderate and 14 patients (43.8%) were severe level. The most common
      symptoms were pruritus (75%), photophobia (50%), lacrimation (37.5%), and
      secretions (28.1%). 65.6% had a family history of atopy and 84.4% had an allergic
      comorbidity. Aeroallergen skin tests were found positive in 25 patients (78.1%).
      All patients had initiated ocular treatment by the time the survey of quality of
      life was conducted; but, they still had low quality of life scores in the 5
      domains assessed. When the scores were evaluated by gender, the only
      statistically significant difference was found in the domain of family life and
      free time, which was lower for women. CONCLUSION: The vernal keratoconjunctivitis
      is a disease more prevalent in men. It apparently has an important atopic base in
      our environment, which due to its severe ocular involvement causes a marked
      decrease in the quality of life of the children who present it.

PMID- 29338966
TI  - Family history of venous thromboembolism predicts the diagnosis of acute
      pulmonary embolism in the emergency department.
AB  - BACKGROUND: Pulmonary embolism (PE) clinical decision rules do not consider a
      patient's family history of venous thromboembolism (VTE). We evaluated whether a
      family history of VTE predicts acute PE in the emergency department (ED).
      METHODS: Over a 5.5-year study period, we enrolled a prospective convenience
      sample of patients presenting to an academic emergency department with chest pain
      and/or shortness of breath. We defined a family history of VTE as a first-degree
      relative with previous PE or deep vein thrombosis (DVT). We noted outcomes of
      testing during the patient's ED stay, including the diagnosis of acute PE by
      either computed tomography (CT) or ventilation/perfusion (VQ) scan. RESULTS: Of
      the 3024 study patients, 19.4% reported a family history of VTE and 1.9% were
      diagnosed with an acute PE during the ED visit. Patients with a family history of
      VTE were more likely to be diagnosed with a PE: 3.2% vs. 1.6% (p = 0.009). 82.3%
      of patients were Pulmonary Embolism Rule-out Criteria (PERC) positive, and among
      PERC-positive patients, those with a family history of VTE were more likely to be
      diagnosed with a PE: 3.6% vs. 1.9% (p = 0.016). Of patients who underwent testing
      for PE (33.7%), patients with a family history of VTE were more likely to be
      diagnosed with a PE: 9.4% vs. 4.9% (p = 0.032). CONCLUSION: Patients with a self
      reported family history of VTE in a first-degree relative are more likely to be
      diagnosed with an acute PE in the ED, even among those patients considered to
      have a higher likelihood of PE.

PMID- 29338967
TI  - Real time optic nerve sheath diameter measurement during lumbar puncture.
AB  - Measurement of optic nerve sheath diameter (ONSD) using point of care ultrasound
      has been used to indirectly assess the intracranial pressure (ICP) particularly
      in conditions where it is raised. Direct pressure measurements using probes
      reaching the ventricle system correlated with ONSD using ultrasound. Attempts
      were made to measure the ONSD pre and post lumbar puncture (LP) after draining
      cerebrospinal fluid (CSF) as well as post ventricular shunt placement. We report
      ONSD measurement and demonstrate dynamic changes during LP in a patient with
      known idiopathic intracranial hypertension (IIH).

PMID- 29338968
TI  - An alternative tool for triaging patients with possible acute coronary symptoms
      before admission to a chest pain unit.
AB  - OBJECTIVE: This study aimed to develop a triage tool to more effectively triage
      possible ACS patients presenting to the emergency department (ED) before
      admission to a protocol-driven chest pain unit (CPU). METHODS: Seven hundred
      ninety-three clinical cases, randomly selected from 7962 possible ACS cases, were
      used to develop and test an ACS triage model using cluster analysis and stepwise
      logistic regression. RESULTS: The ACS triage model, logit (suspected ACS
      patient)=-5.283+1.894*chest pain+1.612*age+1.222*male+0.958*proximal radiation
      pain+0.962*shock+0.519*acute heart failure, with a threshold value set at 2.5,
      was developed to triage patients. Compared to four existing methods, the chest
      pain strategy, the Zarich's strategy, the flowchart, and the heart broken index
      (HBI), the ACS triage model had better performance. CONCLUSION: This study
      developed an ACS triage model for triaging possible ACS patients. The model could
      be used as a rapid tool in EDs to reduce the workloads of ED nurses and
      physicians in relation to admissions to the CPU.

PMID- 29338969
TI  - Current and Future Challenges of Radiation Oncology in Iran: A Report from the
      Iranian Society of Clinical Oncology.
AB  - AIMS: Growth of the cancer incidence rate in Iran has been very high in recent
      years. Therefore, the Iranian health care system should be prepared for the
      treatment of a huge number of patients in the foreseeable future. One of the most
      important treatment options for cancer is radiation. However, there is no
      comprehensive information on infrastructure for radiation oncology in this
      country. MATERIALS AND METHODS: In 2015, a questionnaire was designed by the
      Iranian Society of Clinical Oncology (ISCO) and all radiation oncology centres in
      the country were visited to determine four important components of radiation
      oncology services, including facilities, equipment, personnel and patients.
      RESULTS: In 2015, 94 radiotherapy centres were identified in Iran. Sixty-one
      centres were fully operational, six centres were commissioning, 26 centres were
      under construction and one was inactive. Among the fully operational radiotherapy
      centres, 54 offered three-dimensional conformal radiotherapy and two-dimensional
      radiotherapy, eight offered brachytherapy, two intensity-modulated radiotherapy,
      two intraoperative radiotherapy, ostereotactic radiosurgery, two hyperthermia and
      59 chemotherapy. Moreover, the survey identified 110 linear accelerators, 25
      cobalt-60, one gamma knife, 21 remote brachytherapy afterloaders and six
      orthovoltage units. Treatment planning equipment included 15 graphy simulators,
      19 dedicated computed tomography simulators, 22 multileaf collimator and 12
      electronic portal imaging devices. Moreover, in 2015, 243 clinical oncologists
      participated in the treatment of 42 350 cancer patients in need of radiotherapy,
      which is about one radiation oncologist for 175 patients. During 2010-2015,
      number of cobalt-60 reduced 70%, from 25 units to 8 units. CONCLUSIONS: There is
      a significant gap between Iran's available facilities for radiation therapy and
      international standards. Moreover, during international economic sanctions
      against Iran this gap widened.

PMID- 29338970
TI  - Baicalein and baicalin alleviate acetaminophen-induced liver injury by activating
      Nrf2 antioxidative pathway: The involvement of ERK1/2 and PKC.
AB  - Acetaminophen (APAP)-induced hepatotoxicity is the main cause of drug-induced
      liver injury. This study investigated the protection of baicalin and its aglycone
      baicalein against APAP-induced hepatotoxicity and its mechanism. Baicalein and
      baicalin alleviated APAP-induced hepatotoxicity both in vitro and in vivo.
      Moreover, this baicalin-provided protection was not diminished in hepatocytes or
      mice treated with beta-glucuronidase inhibitor. Results of liver glutathione
      (GSH) and reactive oxygen species (ROS) formation demonstrated the alleviation of
      baicalein and baicalin on APAP-induced liver oxidative stress injury. Baicalein
      and baicalin induced the activation of nuclear factor erythroid 2-related factor
      2 (Nrf2) and increased the expression of its downstream antioxidant genes.
      Baicalein and baicalin-provided protection was diminished after the application
      of Nrf2 siRNA in hepatocytes and Nrf2 knock-out mice. Molecular docking results
      indicate the potential interaction of baicalein and baicalin with kelch-like ECH
      associated protein-1 (Keap1). Baicalein and baicalin induced the sustained
      phosphorylation of extracellular regulated protein kinases (ERK)1/2 and protein
      kinase C (PKC). Moreover, ERK1/2 and PKC inhibitors both abrogated Nrf2
      phosphorylation and its subsequent activation, and the protection against APAP
      induced hepatotoxicity induced by baicalein and baicalin. In summary, baicalein
      and baicalin alleviate APAP-induced hepatotoxicity by activating Nrf2 via
      blocking the binding of Nrf2 with Keap1 and inducing Nrf2 phosphorylation. ERK1/2
      and PKC are both critical for regulating the phosphorylation of Nrf2 induced by
      baicalein or baicalin.

PMID- 29338971
TI  - Atorvastatin impaired glucose metabolism in C2C12 cells partly via inhibiting
      cholesterol-dependent glucose transporter 4 translocation.
AB  - Skeletal muscle accounts for approximately 75% of glucose disposal in body and
      statins impair glucose metabolism. We aimed to investigate the effect of
      atorvastatin on glucose metabolism in C2C12 cells. Glucose metabolism and
      expression of glucose transporter 4 (GLUT4) and hexokinase II (HXKII) were
      measured following incubation with atorvastatin or pravastatin. Roles of
      cholesterol in atorvastatin-induced glucose metabolism impairment were
      investigated via adding cholesterol or mevalonic acid and confirmed by
      cholesterol depletion with methyl-beta-cyclodextrin. Hypercholesterolemia mice
      induced by high fat diet (HFD) feeding, orally received atorvastatin (6 and 12
      mg/kg) or pravastatin (12 mg/kg) for 22 days. Results showed that atorvastatin
      not pravastatin concentration-dependently impaired glucose consumption, glucose
      uptake and GLUT4 membrane translocation in C2C12 cells without affecting
      expression of HXKII or total GLUT4 protein. The atorvastatin-induced alterations
      were reversed by cholesterol or mevalonic acid. Cholesterol depletion exerted
      similar impact to atorvastatin, which could be alleviated by cholesterol
      supplement. Glucose consumption or GLUT4 translocation was positively associated
      with cellular cholesterol levels. In HFD mice, atorvastatin not pravastatin
      significantly increased blood glucose levels following glucose or insulin dose
      and decreased expression of membrane not total GLUT4 protein in muscle. Glucose
      exposure following glucose or insulin dose was negatively correlated to muscular
      free cholesterol concentration. Expression of membrane GLUT4 protein was
      positively related to free cholesterol in muscle. In conclusion, atorvastatin
      impaired glucose utilization in muscle cells partly via inhibiting GLUT4 membrane
      translocation due to inhibition of cholesterol synthesis by atorvastatin, at
      least, partly contributing to glucose intolerance in HFD mice.

PMID- 29338972
TI  - HDL-C, ApoA1 and VLDL-TG as biomarkers for the carotid plaque presence in
      patients with metabolic syndrome.
AB  - AIM: Hypercholesterolemia and hyper LDL-C are associated with the atherosclerosis
      (AS). The current study was performed to evaluate the implication of the others
      lipoproteins (HDL, LDL, VLDL) and apolipoproteins (ApoA1, ApoB100) with
      subclinical atherosclerosis (carotid plaque) in patients with metabolic syndrome
      (MetS) free from cardiovascular disease (CVD). METHODS: Prospective transversal
      study was conducted in patients with MetS free from cardiovascular disease (CVD).
      The lipids, lipoproteins and apolipoproteins were measured. The lipoproteins
      (HDL, LDL, VLDL) were obtained by the precipitation method. The carotid plaque
      (CP) was evaluated by ultrasonography, method for assessing AS. Logistic
      regression and analysis tree were used to look for the association and the
      incrimination of the lipoproteins with the presence of CP. RESULTS: The CP
      incidence was 60% among the participants, 34.29% on the right and the left plaque
      against 25.71% for only one plaque. The HDL-C was the only lipoprotein associated
      with the CP after adjustment of the age, the sex and BMI (OR: 0.007 P: 0.046)
      with the logistic regression analysis, HDL-C (<0.35 g/l), ApoA1 (<1.43 g/l) and
      VLDL-TG (>0.656 g/l) are implicated in the presence of CP with the analysis tree
      analysis. CONCLUSION: Lower level of HDL-C is associated with CP, HDL-C, ApoA1,
      and high level VLDL-TG but not total cholesterol, and LDL-Care useful parameters
      in the assessment of initial atherosclerosis in metabolic syndrome.

PMID- 29338973
TI  - Asthma-COPD overlap: A Portuguese survey.
AB  - INTRODUCTION: The overlap between asthma and chronic obstructive pulmonary
      disease (COPD) (ACO) has been discussed for many years but clinical
      recommendations for this entity have been diverse. This study is intended to
      reach a consensus on diagnosis, treatment and patient orientation for ACO, within
      the Portuguese medical community. METHODS: This study was conducted by a
      multidisciplinary panel of experts from three distinct medical specialties
      (Pulmonology, Family Medicine and Immunoallergology). This panel selected a total
      of 190 clinicians, based on their expertise in obstructive airway diseases, to
      participate in a Delphi structured survey with three rounds of questionnaires.
      These results were ultimately discussed, in a meeting with the panel of experts
      and some of the study participants, and consensus was reached in terms of
      classification criteria, treatment and orientation of ACO patients. RESULTS: The
      majority of clinicians (87.2%) considered relevant the definition of an overlap
      entity between asthma and COPD. A consensus was achieved on the diagnosis of ACO 
      presence of simultaneous clinical characteristics of asthma and COPD together
      with a fixed airflow obstruction (FEV1/FVC<0.7) associated with 2 major criteria
      (previous history of asthma; presence of a previous history of smoking exposure
      and/or exposure to biomass combustion; positive bronchodilation test (increase in
      FEV1 of at least 200mL and 12%) on more than 1 occasion) plus 1 minor criteria
      (history of atopy; age >=40 years; peripheral eosinophilia (>300eosinophils/MUL
      or >5% of leukocytes); elevation of specific IgEs or positive skin tests for
      common allergens). A combination of inhaled corticosteroid (ICS) with long-acting
      beta2-agonist (LABA) or long-acting muscarinic antagonist (LAMA) was considered
      as first line pharmacological treatment. Triple therapy with ICS plus LABA and
      LAMA should be used in more severe or symptomatic cases. Non-pharmacological
      treatment, similar to what is recommended for asthma and COPD, was also
      considered highly important. A hospital referral of ACO patients should be made
      in symptomatic or severe cases or when there is a lack of diagnostic resources.
      CONCLUSIONS: This study highlights the relevance of defining ACO, within the
      Portuguese medical community, and establishes diagnostic criteria that are
      important for future interventional studies. Recommendations on treatment and
      patient's orientation were also achieved.

PMID- 29338974
TI  - Usefulness of the "grand-piano sign" for determining femoral rotational alignment
      in total knee arthroplasty.
AB  - BACKGROUND: The "grand-piano sign" is a well-known indicator of proper rotational
      femoral alignment. We investigated changes in the shape of the femoral anterior
      cutting plane by changing the rotational alignment, anterior portion depth, and
      cutting plane flexion angle. METHODS: We simulated various cutting planes after
      cutting the anterior portion of the femur next to the distal femoral osteotomy in
      50 patients with varus knee and also a femoral anterior osteotomy with four
      degree (S group) and seven degree (T group) flexion angles regarding the
      mechanical axis. We defined the final cutting plane as the farthest position that
      we could reach without making a notch and the precutting plane as two millimeters
      anterior from the final cutting plane. The simulated resection plane was rotated
      to produce external and internal rotation angles of 0 degrees , three degrees,
      and five degrees relative to the surgical transepicondylar axis (SEA). We
      investigated medial and lateral portions of the femoral anterior cutting plane
      length ratio (M/L). RESULTS: When we cut parallel to SEA, M/L was 0.67+/-0.09 and
      0.62+/-0.12 in the T and S groups, respectively. M/L was approximately 0.8 and
      0.5 with five degree internal and external rotations, respectively (P<0.01). On
      comparing final cutting and precutting planes, there were no significant
      differences in M/L without five degree external rotation in the T group and no
      significant difference in any case in the S group (P>0.01). CONCLUSIONS: The
      ideal M/L of the femoral anterior cutting plane was 0.62-0.67. M/L did not change
      with a precutting plane in almost all rotational patterns.

PMID- 29338976
TI  - WASP (Write a Scientific Paper) using Excel - 4: Histograms.
AB  - Plotting data into graphs is a crucial step in data analysis as part of an
      initial descriptive statistics exercise since it gives the researcher an overview
      of the shape and nature of the data. Outlier values may also be identified, and
      these may be incorrect data, or true and important outliers. This paper explains
      how to access Microsoft Excel's Analysis Toolpak and provides some pointers for
      the utilisation of the histogram tool within the Toolpak.

PMID- 29338975
TI  - Critical effects of polar fluorescent probes on the interaction of DHA with POPC
      supported lipid bilayers.
AB  - The understanding of lipid bilayer structure and function has been advanced by
      the application of molecular fluorophores. However, the effects of these probe
      molecules on the physicochemical properties of membranes being studied are poorly
      understood. A quartz crystal microbalance with dissipation monitoring instrument
      was used in this work to investigate the impact of two commonly used fluorescent
      probes, 1-palmitoyl-2-{12-[(7-nitro-2-1,3-benzoxadiazol-4-yl)amino]dodecanoyl}-sn
      glycero-3-phosphocholine (NBD-PC) and 1,2-dipalmitoyl-sn-glycero-3
      phosphoethanolamine-n-(lissamine rhodamine-B-sulfonyl) (Lis-Rhod PE), on the
      formation and physicochemical properties of a 1-palmitoyl-2-oleoyl-sn-glycero-3
      phosphocholine supported lipid bilayer (POPC-SLB). The interaction of the POPC
      SLB and fluorophore-modified POPC-SLB with docosahexaenoic acid, DHA, was
      evaluated. The incorporation of DHA into the POPC-SLB was observed to
      significantly decrease in the presence of the Lis-Rhod PE probe compared with the
      POPC-SLB. In addition, it was observed that the small concentration of DHA
      incorporated into the POPC:NBD-PC SLB can produce rearrangement processes
      followed by the lost not only of DHA but also of POPC or NBD-PC molecules or both
      during the washing step. This work has significant implications for the
      interpretation of data employing fluorescent reporter molecules within SLBs.

PMID- 29338977
TI  - WASP (Write a Scientific Paper) using Excel - 2: Pivot tables.
AB  - Data analysis at the descriptive stage and the eventual presentation of results
      requires the tabulation and summarisation of data. This exercise should always
      precede inferential statistics. Pivot tables and pivot charts are one of Excel's
      most powerful and underutilised features, with tabulation functions that
      immensely facilitate descriptive statistics. Pivot tables permit users to
      dynamically summarise and cross-tabulate data, create tables in several
      dimensions, offer a range of summary statistics and can be modified interactively
      with instant outputs. Large and detailed datasets are thereby easily manipulated
      making pivot tables arguably the best way to explore, summarise and present data
      from many different angles. This second paper in the WASP series in Early Human
      Development provides pointers for pivot table manipulation in ExcelTM.

PMID- 29338978
TI  - Non-risk-adapted Surveillance for Stage I Testicular Cancer: Critical Review and
      Summary.
AB  - CONTEXT: Cancer-specific survival for men with clinical stage I testicular cancer
      (CSITC) is uniformly excellent. Non-risk-adapted active surveillance (NRAS) is a
      management strategy for CSITC to minimize overtreatment and avoid possible long
      term side effects of adjuvant therapy. OBJECTIVE: To review the evidence
      regarding oncologic outcomes for men with CSITC undergoing NRAS and discuss
      ongoing controversies in the management of CSITC. EVIDENCE ACQUISITION:
      MEDLINE/PubMed, Embase, and the Cochrane Central Register of Controlled Trials
      were searched from January 1, 1987 through January 1, 2017. EVIDENCE SYNTHESIS: A
      total of 68 studies were included in the critical review. The rationale for NRAS,
      oncologic outcomes, surveillance protocols, and comparative efficacy of risk
      adjusted active surveillance (AS) were reported with strength of evidence and
      risk of bias evaluated. Cancer-specific survival approaches 100% for men with
      CSITC undergoing NRAS. Active treatment is limited to 20-30% of patients who will
      recur; these patients will require salvage chemotherapy and possible
      retroperitoneal lymph node dissection. Existing AS protocols include imaging and
      laboratory evaluations that are initially intensive but less frequent with
      increasing follow-up. CONCLUSIONS: NRAS is an attractive management option for
      men with CSITC, which maintains outstanding long-term cancer cure while sparing
      most patients treatment by avoiding prophylactic chemotherapy, radiation, or
      surgery. PATIENT SUMMARY: Men with clinically localized (stage I) testicular
      cancer have an excellent prognosis, regardless of management. Non-risk-adapted
      active surveillance is an attractive management option where only patients
      destined to relapse will receive any treatment following orchiectomy. However,
      individual patient preferences should be discussed in selecting a management
      strategy.

PMID- 29338979
TI  - Dysregulated autophagy in restrictive cardiomyopathy due to Pro209Leu mutation in
      BAG3.
AB  - Myofibrillary myopathies (MFM) are hereditary myopathies histologically
      characterized by degeneration of myofibrils and aggregation of proteins in
      striated muscle. Cardiomyopathy is common in MFM but the pathophysiological
      mechanisms are not well understood. The BAG3-Pro209Leu mutation is associated
      with early onset MFM and severe restrictive cardiomyopathy (RCM), often
      necessitating heart transplantation during childhood. We report on a young male
      patient with a BAG3-Pro209Leu mutation who underwent heart transplantation at
      eight years of age. Detailed morphological analyses of the explanted heart tissue
      showed intracytoplasmic inclusions, aggregation of BAG3 and desmin,
      disintegration of myofibers and Z-disk alterations. The presence of undegraded
      autophagosomes, seen by electron microscopy, as well as increased levels of p62,
      LC3-I and WIPI1, detected by immunohistochemistry and western blot analyses,
      indicated a dysregulation of autophagy. Parkin and PINK1, proteins involved in
      mitophagy, were slightly increased whereas mitochondrial OXPHOS activities were
      not altered. These findings indicate that altered autophagy plays a role in the
      pathogenesis and rapid progression of RCM in MFM caused by the BAG3-Pro209Leu
      mutation, which could have implications for future therapeutic strategies.

PMID- 29338980
TI  - Prevalence of Bovine Aortic Arch Variant in Patients with Aortic Dissection and
      its Implications in the Outcome of Patients with Acute Type B Aortic Dissection.
AB  - OBJECTIVE/BACKGROUND: To investigate the prevalence of bovine arch (BA) among
      patients with type A and B aortic dissection, and to provide insight into the
      implication of this variation on the outcome of patients with acute or subacute
      type B aortic dissection (a/sTBAD). METHODS: This retrospective cohort analysis
      includes patients with a/sTBAD admitted between January 2006 and December 2016.
      Computed tomographic angiograms (CTAs) of patients referred because of type A
      aortic dissection were also re-evaluated with regard to the presence of BA. As a
      control group, 110 oncological patients who had undergone a chest CTA for disease
      staging during the study period were enrolled. A total of 154 patients with
      a/sTBAD and 168 with type A aortic dissection were identified during the study
      period. RESULTS: An overall prevalence of 17.6% for BA variants was revealed. The
      comparison between patients with aortic dissection and the control group showed
      no statistically significant difference in BA prevalence (17.7% vs. 17.3%; p =
      1.0). No statistically significant difference in BA prevalence was observed when
      comparing patients with type A aortic dissection with those with type B aortic
      dissection (16.6% vs. 18.8%; p = .66). During a median follow-up period of 27.8
      months, 30 patients died. The mortality rate among patients presenting a BA
      variant was 34.5%, whereas among patients without, it was 16.0% (p = .04).
      Multivariate analysis revealed the presence of a BA as an independent predictor
      of mortality (adjusted odds ratio 3.4, 95% confidence interval 1.2-9.8).
      CONCLUSION: The BA should be considered as a predictor of the outcome for
      patients with type B aortic dissection.

PMID- 29338981
TI  - Reproducibility and agreement of different non-invasive methods of endothelial
      function assessment.
AB  - Flow-mediated dilatation (FMD) is an established, but investigator-demanding
      method, used to non-invasively determine nitric oxide (NO)-dependent endothelial
      function in humans. Local thermal hyperemia (LTH) or post-occlusive reactive
      hyperemia (PORH) of the skin measured with a laser Doppler flow imager may be a
      less demanding alternative of FMD. We investigated the reproducibility of the
      different measures of vascular function, their interrelationship and the NO
      dependency of LTH. Measurements were performed twice in 27 healthy men (8
      smokers), one week apart. Local application of NG-monomethyl-l-arginine (L-NMMA)
      by means of iontophoresis was used to determine the NO-dependency of LTH. Using L
      NMMA, the peak and plateau responses of LTH were reduced by 31% (p < .001) and
      65% (<0.001), respectively. For all measurements the coefficient of variation
      (CV) was higher in smokers than in non-smokers. For non-smokers the CV of FMD was
      12%, of LTH peak response 17%, of LTH plateau response 12%, of PORH peak response
      14% and of PORH area under the curve response 11%. FMD correlated weakly with the
      PORH peak and area under the curve response (r = 0.39 and 0.43, p < .05), whereas
      the LTH-plateau response correlated with the PORH peak response (r = 0.68, p <
      .01) in non-smokers, but FMD and LTH peak or plateau responses were unrelated. In
      conclusion, the LTH plateau response is for two-third NO-dependent, but unrelated
      to FMD. Furthermore, despite easy to perform the LTH responses are not more
      reproducible than FMD. Given the weak associations, the different methods of
      vascular function assessment are not interchangeable.

PMID- 29338982
TI  - Involvement of peripheral alpha2A adrenoceptor in the acceleration of
      gastrointestinal transit and abdominal visceral pain induced by intermittent
      deprivation of REM sleep.
AB  - Many studies have associated sleep alterations with the severity of irritable
      bowel syndrome (IBS) symptoms, but the direct pathophysiological relationship has
      not been clarified. In addition, alterations in noradrenergic signaling have been
      implicated in the pathophysiology of IBS, and alpha2-adrenoceptors are potential
      treatment targets. We have previously shown that acceleration of gastrointestinal
      transit (GIT) elicited by intermittent rapid eye movement (REM) sleep deprivation
      stress may fulfill the profile of a model of IBS. Moreover, we showed
      hypernoradrenergic function in the brain of sleep-deprived mice. On the other
      hand, acetic acid-induced writhes indicate visceral pain features of IBS model
      animals. In this study, using mice, we investigated whether intermittent REM
      sleep deprivation stress causes changes in acetic acid-induced writhing and
      whether the number of writhes and GIT are improved by administration of the
      hydrophilic clonidine analogue, ST-91. Mice were deprived of REM sleep
      intermittently using the small-platform method (20h/day) for 3days. The
      intermittent REM sleep deprivation stress elicited acceleration of GIT and the
      increased number of writhes was significantly improved by ST-91 treatment. The
      ID50 values of ST-91 on the GIT in cage-control mice and intermittent REM sleep
      deprived mice were 0.24 and 0.70mg/kg, respectively. In addition, the ID50 values
      of ST-91 on the writhes in cage-control mice and intermittent REM sleep-deprived
      mice were 0.52 and 0.73mg/kg, respectively. Further, the expression of alpha2A
      adrenoceptor was decreased in the distal ileum of intermittent REM sleep-deprived
      mice compared to that in cage-control mice. Moreover, the effects of ST-91 on GIT
      and writhes in cage-control and intermittent REM sleep-deprived mice were
      decreased by the administration of BRL44408 (6mg/kg, i.p.), a selective alpha2A
      adrenoceptor antagonist, and not by the administration of imiloxan (3mg/kg,
      i.p.), or JP-1302 (3mg/kg, i.p.), selective alpha2B-and alpha2C-adrenoceptor
      antagonists, respectively. These results suggest that the increase in GIT and
      writhes induced by intermittent REM sleep deprivation stress may serve as a model
      of diarrhea and visceral pain symptoms in IBS. Further, the onset of these
      symptoms may be related to the hypofunction of peripheral alpha2A-adrenoceptor.

PMID- 29338983
TI  - Dipyridamole plus Triflusal versus Triflusal Alone in Infarct Reduction after
      Middle Cerebral Artery Occlusion.
AB  - BACKGROUND AND PURPOSE: The objective of this work is to study the dose-dependent
      effect of combination therapy with dipyridamole and triflusal over that of
      triflusal alone on infarct size after middle cerebral artery occlusion (MCAO)
      ischemia. MATERIALS AND METHODS: Male Wistar rats were subjected to a permanent
      MCAO in the right hemisphere. Rats received triflusal alone and with dipyridamole
      via oral route. Three days after surgery, infarct volumes were measured. RESULTS:
      The lower dose regime of triflusal (10 mg/kg) and dipyridamole (200 mg/kg) caused
      the greatest decrease in infarct size compared with higher dose regime of
      triflusal (30 mg/kg) and dipyridamole (200 mg/kg) (P <.01), triflusal (30 mg/kg)
      alone (P <.07), and vehicle-treated controls. CONCLUSIONS: The lower dose
      combination of dipyridamole and triflusal appears to be more effective than
      triflusal alone after MCAO-induced cerebral ischemia. Therefore, there is a
      strong rationale to continue to examine the protective effects of triflusal and
      dipyridamole after cerebral ischemia.

PMID- 29338984
TI  - Practical guidelines for performing laparoscopic liver resection based on the
      second international laparoscopic liver consensus conference.
AB  - Laparoscopic liver resection is rapidly increasing, and certain types of
      resection are considered standard procedures for liver resection, especially for
      small malignant tumors located on the liver surface or in the anterolateral
      segments of the liver. Several specialized centers have performed many types of
      highly complex hepatectomies, anatomical resections, and laparoscopic donor
      hepatectomies. Even though several international consensus conferences and expert
      meetings have been held, until now there have been no practical guidelines for
      beginners or experts conducting laparoscopic liver resection. We describe here
      practical guidelines for performing laparoscopic liver resection, including the
      indications, technical considerations, and training required.

PMID- 29338985
TI  - The shikimate pathway enzyme that generates chorismate is not required for the
      development of Plasmodium berghei in the mammalian host nor the mosquito vector.
AB  - In Plasmodium, the shikimate pathway is a potential target for malaria
      chemotherapy owing to its absence in the mammalian host. Chorismate, the end
      product of this pathway, serves as a precursor for aromatic amino acids, Para
      aminobenzoic acid and ubiquinone, and is synthesised by Chorismate synthase (CS).
      Therefore, it follows that the Cs locus may be refractory to genetic
      manipulation. By utilising a conditional mutagenesis system of yeast Flp/FRT, we
      demonstrate an unexpectedly dispensable role of CS in Plasmodium. Our studies
      reiterate the need to establish an obligate reliance on Plasmodium metabolic
      enzymes through genetic approaches before their selection as drug targets.

PMID- 29338986
TI  - Mismanagement of Severe Altitude Illness in a Tertiary Hospital in Nepal: A
      Cautionary Tale.

PMID- 29338987
TI  - Update on the Epidemiology of Scorpion Envenomation in the South of Tunisia.
AB  - INTRODUCTION: Scorpion envenomation is still a frequent occurance in tropical and
      subtropical regions. In Tunisia, multiple studies on scorpion envenoming have
      contributed to an improved understanding of cardiac dysfunction and factors
      predictive of poor prognosis. These previous studies have contributed to the
      current standardized management of envenomed patients. However, the epidemiology
      of scorpion envenoming in Tunisia has not been updated for more than 10 years.
      The aim of this study was to report an update of the epidemiological features of
      scorpion envenomation in the southern region of Tunisia. METHODS: This is a
      retrospective monocentric study including all patients admitted in the emergency
      room for scorpion envenomation. Cases were collected from emergency medical files
      during a 3-year period (2013-2015). The diagnosis of scorpion envenomation was
      made by history of a scorpion sting. All files in which scorpion envenomation was
      not certain were excluded. Data are presented as mean+/-SD with range or
      percentages, as appropriate. RESULTS: We enrolled 282 patients aged 27.4+/-22.8
      years with a 1:1 sex ratio. During surveillance in the emergency room, 39
      patients developed cardiac dysfunction. Overall, 42 patients (14.9%) were at
      stage 3 of severity, and 240 patients (85.1%) had moderate scorpion envenomation
      (stage 2). Only 1 patient died a few hours after admission. In the remaining
      cases, the outcome was good. Our results show the improvement in mortality rates
      even in severe presentations. CONCLUSION: This study found that the outcome of
      scorpion-stung patients has clearly improved. This enhancement can be explained
      by early medical consultation and standardized management of patients with
      predictive factors for cardiac dysfunction.

PMID- 29338988
TI  - Acetazolamide Use in Ultrarunners at Altitude: Issues with Doping.

PMID- 29338989
TI  - Relations Between Self-Reported and Linguistic Monitoring Assessments of
      Affective Experience in an Extreme Environment.
AB  - INTRODUCTION: Approaches for monitoring psychosocial health in challenging
      environments are needed to maintain the performance and safety of personnel. The
      purpose of the present research was to examine the relationship between 2
      candidate methods (self-reported and linguistics) for monitoring affective
      experience during extreme environment activities. METHODS: A single-subject
      repeated-measures design was used in the present work. The participant was a 46
      year-old individual scheduled to complete a self-supported ski expedition across
      Arctic Greenland. The expedition lasted 28 days, and conditions included severe
      cold, low stimulation, whiteouts, limited habitability, and threats to life and
      limb. During the expedition, the participant completed a daily self-report log
      including assessment of psychological health (perceptions of control and affect)
      and a video diary (emotion). Video diary entries were subjected to linguistic
      inquiry and word count analyses before the links between self-report and
      linguistic data across the expedition period were tested. RESULTS: Similarities
      in the pattern of self-reported and linguistic assessments emerged across the
      expedition period. A number of predictable correlations were identified between
      self-reported and linguistic assessments of affective/emotional experience.
      Overall, there was better agreement between self-reports and linguistic analytics
      for indicators of negative affect/emotion. CONCLUSIONS: Future research should
      build on this initial study to further test the links between self-reported
      affect and emotional states monitored via linguistics. This could help develop
      methods for monitoring psychological health in extreme environments and support
      organizational decision making.

PMID- 29338991
TI  - Jellyfish Blooms Causing Mass Envenomations in Aquatic Marathonists: Report of
      Cases in S and SE Brazil (SW Atlantic Ocean).

PMID- 29338990
TI  - Frequency of Polycythemia and Other Abnormalities in a Tibetan Herdsmen
      Population Residing in the Kham Area of Sichuan Province, China.
AB  - INTRODUCTION: The Kham Tibetans are one of several Tibetan ethnic subgroups
      living in the Kham area of China. Because studies on the high-altitude adaptation
      of the Kham people are scant, the main aim of this study is to investigate
      whether the response to hypoxia, especially polycythemia status, in the Kham
      Tibetans is different from other Tibetan ethnic subgroups. METHODS: The primary
      investigation was conducted on 346 native Kham Tibetan adults (268 men and 78
      women) from 3 herdsmen villages located in Hongyuan County situated at an
      altitude of greater than 3600 m. The participants were aged 46.2+/-14.1 (21-82;
      mean+/-SD with range) years. Anthropometric measurements such as weight, height,
      waist circumference, body mass index, and blood pressure, as well as laboratory
      blood tests such as glycosylated hemoglobin, hemoglobin, total cholesterol,
      triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein
      cholesterol, and uric acid were analyzed. RESULTS: The concentrations of
      hemoglobin were 171.3+/-12.9 (66-229) mg.L-1 and 151.4+/-16.4 (86-190) mg.L-1 in
      men and women, respectively. The frequency of polycythemia was found to be 25.5
      and 21.8% in men and women, respectively. Polycythemia was found to be
      significantly associated with glycosylated hemoglobin concentrations,
      hypertension, and hyperuricemia (P=0.002, 0.023, and 0.009, respectively).
      CONCLUSIONS: There is a higher frequency of polycythemia in the Kham Tibetans
      when compared with reported studies from other Tibetan ethnic subgroups living on
      the Qinghai-Tibet plateau.

PMID- 29338992
TI  - Subsequent fertility, pregnancy, and gynecologic outcomes after fetoscopic laser
      therapy for twin-twin transfusion syndrome compared with normal monochorionic
      twin gestations.
AB  - BACKGROUND: An improved survival and quality of life for neonatal survivors after
      fetoscopic laser therapy for twin-twin transfusion syndrome has been reported.
      However, little is known about the medium-term maternal effects after fetoscopic
      laser therapy with respect to reproductive and gynecologic outcomes. OBJECTIVE:
      The objective of this study was to document reproductive, obstetric,
      gynecological, and psychological outcomes in women who underwent fetoscopic laser
      therapy for twin-twin transfusion syndrome. STUDY DESIGN: This was a monocentric
      controlled study on consecutive women who underwent fetoscopic laser therapy for
      twin-twin transfusion syndrome between 2007 and 2013 at the University Hospitals
      Leuven (cases; n = 198). Controls were women followed up during the same time
      period for an uncomplicated monochorionic diamniotic twin pregnancy and with an
      uneventful course (controls; n = 211). All patients received a questionnaire
      inquiring on their fertility, later pregnancies, and gynecological outcomes.
      RESULTS: The response rate was 50.4% (cases: n = 95; controls: n = 109). Most
      baseline characteristics were similar across both groups. Women in the fetoscopic
      laser therapy group attempted a new pregnancy more frequently (34% [31 of 92] vs
      21% [22 of 107] in controls; P < .05) and became pregnant more often (100% [31 of
      31] vs 82% [18 of 22]; P < .05).We observed a shorter interpregnancy interval in
      cases than controls (median interval, 12 [interquartile range, 5-27] vs 24
      [interquartile range, 15-30] months) (P < .05). This was also observed in cases
      who lost one or both fetuses or babies in the index pregnancy (median interval, 9
      [interquartile range, 3.5-25.5] months; P < .05). The complication rate during
      subsequent pregnancies (26% [8 of 31] vs 11% [2 of 19]; P = .194) and at delivery
      (17% [5 of 30] vs 11% [2 of 19]; P = .554) were comparable. More women who
      underwent fetoscopic laser coagulation reported relevant psychological symptoms
      (44% [40 of 92] vs 21% [23 of 107]; P < .05). When only women in whom there was a
      double-surviving twin pair were considered, there were no differences in
      psychological symptoms compared with controls (16% [15 of 55] vs 21% [23 of 107];
      P = .411). Gynecological problems were equally frequent in both groups (20% [18
      of 92] vs 31% [33 of 107]; P = .069). CONCLUSION: No adverse medium-term maternal
      effects with respect to fertility, obstetric, and gynecological outcomes were
      observed after fetoscopic laser therapy. However, these women reported more
      psychological or emotional problems than women with monochorionic diamniotic who
      did not have laser therapy, in particular when this was complicated by a fetal
      loss.

PMID- 29338993
TI  - Peritoneal sarcomatosis 5 years after laparoscopic morcellation of uterine
      leiomyoma.

PMID- 29338994
TI  - Both patients and maternity care providers can benefit from payment reform: four
      steps to prepare.
AB  - Many Medicaid programs and private health plans are implementing new models of
      maternity care reimbursement, and clinicians face mounting pressure to
      demonstrate high-quality care at a lower cost. Clinicians will be better prepared
      to meet these challenges with a fuller understanding of new payment models and
      the opportunities they present. We describe the structure of maternity care
      episode payments and recommend 4 ways that clinicians can prepare for success as
      value-based payment models are implemented: identify opportunities to improve
      outcomes and experience, measure quality, reduce waste, and work in teams across
      settings.

PMID- 29338995
TI  - Echocardiography as a Clinical Stratification Tool in Venovenous Extracorporeal
      Membrane Oxygenation.

PMID- 29338996
TI  - Incidence and Predictors of Postoperative Need for High-Dose Inotropic Support in
      Patients Undergoing Cardiac Surgery for Infective Endocarditis.
AB  - OBJECTIVE: Patients with infective endocarditis undergoing cardiac surgery are a
      high-risk population. Few data on incidence and predictors of need for high-dose
      inotropic support in this setting are currently available. DESIGN: Retrospective
      study. SETTING: Tertiary-care hospital. PARTICIPANTS: Ninety consecutive patients
      undergoing cardiac surgery for infective endocarditis. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: Baseline, intraoperative and outcome data were
      collected. Stepwise multiple logistic regression analysis was performed to
      identify preoperative predictors of postoperative hemodynamic support. High-dose
      postoperative inotropic support was defined as inotropic score >10 (calculated as
      dobutamine dose (in ug/kg/min) + dopamine dose (in ug/kg/min) + (epinephrine dose
      [in ug/kg/min] * 100) + (norepinephrine dose [in ug/kg/min] * 100) + (milrinone
      dose [in ug/kg/min] * 10) + (vasopressin dose [in U/kg/min] * 10 000) +
      (levosimendan dose [in ug/kg/min] * 50) or need for mechanical circulatory
      support at intensive care unit admission. Postoperative high-dose inotropic or
      mechanical circulatory support was required in 57 cases (61%). Stepwise multiple
      logistic regression identified 5 variables independently associated with need for
      postoperative circulatory support: male sex (odds ratio [OR] = 10.9), surgery
      duration (OR for every minute increase = 1.01), impairment of kidney function
      (eGFR <60 mL/min/m2 - OR = 19), preoperative new-onset heart failure (defined by
      clinical, imaging and laboratory parameters - OR = 5.30), and low preoperative
      platelet count (for every 1*103/MUl increase - OR = 0.99). CONCLUSIONS: Patients
      undergoing cardiac surgery for infective endocarditis are at high risk for
      postoperative hemodynamic instability. Preoperative organ failure is an important
      determinant for postoperative hemodynamic instability.

PMID- 29338997
TI  - Meta-analysis of the Sources of Bleeding after Adult Cardiac Surgery.
AB  - OBJECTIVE: The aim of this study was to pool data on the proportion and
      prognostic impact of sources of bleeding in patients requiring re-exploration
      after adult cardiac surgery. DESIGN: Systematic review of the literature and meta
      analysis. SETTING: Multistitutional study. MEASUREMENTS AND MAIN RESULTS: A
      literature review was performed to identify studies published since 1990
      evaluating the outcome after reoperation for bleeding or tamponade after adult
      cardiac surgery. Eighteen studies including 5,1497 patients fulfilled the
      selection criteria. Reoperation for bleeding/tamponade was performed in 2,455
      patients (4.6%; 95% confidence interval [CI] 3.9%-5.2%, I2 92%). These had a
      significantly higher risk of in-hospital/30-day mortality compared with patients
      not reoperated for bleeding (pooled rates: 9.3% v 2.3%; risk ratio 3.30; 95% CI
      2.52-4.32; I2 47%; 8 studies; 25,463 patients). Surgical sites of bleeding were
      identified in 65.7% of cases (95% CI 58.3%-73.2%; I2 94%), cardiac site bleeding
      in 40.9% of cases (95% CI 29.7%-52.0%; I2 94%), and mediastinal/sternum site
      bleeding in 27.0% of cases (95% CI 16.8%-37.3%; I2 94%). The main sites of
      bleeding were the body of the graft (20.2%), the sternum (17.0%), vascular
      sutures (12.5%), the internal mammary artery harvest site (13.0%), and
      anastomoses (9.9%). In metaregression, surgical site bleeding was associated with
      a lower risk of in-hospital/30-day mortality compared with diffuse bleeding (p =
      0.003). CONCLUSIONS: Surgical site bleeding is identified in two-thirds of
      patients undergoing re-exploration after adult cardiac surgery. Meticulous
      surgical technique and systematic intraoperative checking of potential surgical
      sites of bleeding at the time of the original cardiac surgery may reduce the risk
      of such a severe complication.

PMID- 29338998
TI  - General Anesthesia Versus Conscious Sedation for Transcatheter Aortic Valve
      Replacement-An Analysis of Current Outcome Data.

PMID- 29338999
TI  - Implantable Left Ventricular Assist Device Therapy-Recent Advances and Outcomes.

PMID- 29339000
TI  - A New Way to Secure Internal Jugular Central Catheters.

PMID- 29339001
TI  - Does the surgical approach for treating mandibular condylar fractures affect the
      rate of seventh cranial nerve injuries? A systematic review and meta-analysis
      based on a new classification for surgical approaches.
AB  - PURPOSE: The purpose of this study was to determine the rate of facial nerve
      injury (FNI) when performing (ORIF) of mandibular condylar fractures by different
      surgical approaches. MATERIALS AND METHODS: A systematic review and meta-analysis
      were performed that included several databases with specific keywords, a
      reference search, and a manual search for suitable articles. The inclusion
      criteria were all clinical trials, with the aim of assessing the rate of facial
      nerve injuries when (ORIF) of mandibular condylar fractures was performed using
      different surgical approaches. The main outcome variable was transient facial
      nerve injury (TFNI) and permanent facial nerve injury (PFNI) according to the
      fracture levels, namely: condylar head fractures (CHFs), condylar neck fractures
      (CNFs), and condylar base fractures (CBFs). For studies where there was no
      delineation between CNFs and CBFs, the fractures were defined as CNFs/CBFs. The
      dependent variables were the surgical approaches. RESULTS: A total of 3873
      patients enrolled in 96 studies were included in this analysis. TFNI rates
      reported in the literature were as follows: A) For the transoral approach: a) for
      strictly intraoral 0.72% (1.3 in CNFs and 0% for CBFs); b) for the transbuccal
      trocar instrumentation 2.7% (4.2% in CNFs and 0% for CBFs); and c) for
      endoscopically assisted ORIF 4.2% (5% in CNFs, and 4% in CBFs). B) For low
      submandibular approach 15.3% (26.1% for CNFs, 11.8% for CBFs, and 13.7% for
      CNFs/CBFs). C) For the high submandibular/angular subparotid approach with
      masseter transection 0% in CBFs. D) For the high submandibular/angular
      transmassetric anteroparotid approach 0% (CNFs and CBFs). E) For the transparotid
      retromandibular approach a) with nerve facial preparation 14.4% (23.9% in CNFs,
      11.8% in CBFs and 13.7% for CNFs/CBFs); b) without facial nerve preparation 19%
      (24.3% for CNFs and 10.5% for CBFs). F) For retromandibular transmassetric
      anteroparotid approach 3.4% in CNFs/CBFs. G) For retromandibular transmassetric
      anteroparotid approach with preauricular extension 2.3% for CNFs/CBFs. H) For
      preauricular approach a) deep subfascial dissection plane 0% in CHFs b) for
      subfascial approach using traditional preauricular incision 10% (8.5% in CHFs and
      11.5% in CNFs). I) For retroauricular approach 3% for CHFs. PFNI rates reported
      in the literature were as follows: A) for low submandibular approach 2.2%, B) for
      retromandibular transparotid approach 1.4%; C) for preauricular approach 0.33%;
      D) for high submandibular approach 0.3%; E) for deep retroparotid approach 1.5%.
      CONCLUSION: According to published data for CHFs, a retroauricular approach or
      deep subfascial preauricular approach was the safest to protect the facial nerve.
      For CNFs, a transmassetric anteroparotid approach with retromandibular and
      preauricular extension was the safest approach to decrease risk of FNI. For CBFs,
      high submandibular incisions with either transmassetric anteroparotid approach
      with retromandibular or transmassetric subparotid approach, followed by intraoral
      (with or without endoscopic/transbuccal trocar) were the safest approaches with
      respect to decreased risk of FNI.

PMID- 29339002
TI  - Development of a new three-directional distractor system for the correction of
      maxillary transverse and sagittal deficiency.
AB  - PURPOSE: Class 3 malocclusions with maxillary deficiency, which are treated
      surgically and/or ordonotically, are common among adult patients. The aim of this
      study was to develop a three-directional bone-borne distractor that would allow
      the transverse expansion and sagittal advancement of the maxilla simultaneously.
      MATERIALS AND METHODS: Computed tomography images of a patient with maxillary
      deficiency were transmitted to a software program, and a distractor was designed
      with different sizes (D1, D2, D3) and manufactured from titanium alloy. Y-shape
      segmental osteotomies were performed on the model, and vertical bite forces were
      applied. The biomechanical properties were evaluated by using the finite element
      method. RESULTS: The highest von Mises stress value on the body of the distractor
      was seen in D2 (D2>D3>D1), with 234 N bite forces. D2 had maximum stress
      distribution on maxillary bone under 234 N and 93 N (D2>D1>D3). No difference was
      found among the plastic deformation rates according to biomechanical test
      results. CONCLUSION: A three-directional bone-borne palatal distractor was
      produced, and this distractor system can be used for the treatment of skeletal
      class 3 patients with maxillary hypoplasia for its advantages of shortening the
      overall treatment time and reducing the scar formation. However, further animal
      and clinical studies are essential to determine the biological response of soft
      and hard tissues.

PMID- 29339003
TI  - Direct recovery of Bacillus subtilis xylanase from fermentation broth with an
      alcohol/salt aqueous biphasic system.
AB  - Xylanase enzyme degrades linear polysaccharide beta-1,4 xylan and the
      hemicellulose of the plant cell wall. There is a growing demand in finding a cost
      effective alternative for industrial scale production of xylanase with high
      purity for pharmaceutical applications. In this study, an alcohol/salt aqueous
      biphasic system (ABS) was adopted to recover xylanase from the Bacillus subtilis
      fermentation broth. The effects of several ABS parameters such as types and
      concentrations of alcohols and salts (i.e., sulphate, phosphate, and citrate),
      amount of crude loading and pH of the system on the recovery of xylanase were
      investigated. Partition coefficient of xylanase (KE), selectivity (S) and yield
      (YT) of xylanase in top phase of the ABS were measured. Highest KE (6.58 +/-
      0.05) and selectivity (4.84 +/- 0.33) were recorded in an ABS of pH 8 composed of
      26% (w/w) 1-propanol, 18% (w/w) ammonium sulphate. High YT of 71.88% +/- 0.15 and
      a purification fold (PFT) of 5.74 +/- 0.33 were recorded with this optimum
      recovery of xylanase using alcohol/salt ABS. The purity of xylanase recovered was
      then qualitatively verified with sodium dodecyl sulphate (SDS) gel
      electrophoresis. The SDS profile revealed the purified xylanase was successfully
      obtained in the top phase of the one-step 1-propanol/sulphate ABS with a distinct
      single band.

PMID- 29339004
TI  - Differential activation of brain areas in children with developmental
      coordination disorder during tasks of manual dexterity: An ALE meta-analysis.
AB  - Recent neuroimaging studies have reported atypical neural activation in children
      with Developmental Coordination Disorder (DCD) during tasks assessing manual
      dexterity. However, small sample sizes and subtle differences in task parameters
      have led to inconsistent findings, rendering interpretation difficult. The aim of
      the present meta-analysis was to quantitatively summarize this body of evidence
      using activation likelihood estimation (ALE) analysis to identify reliable
      regions of differential neural activation in children with DCD, compared to age
      matched controls. Seven studies that adopted fMRI to compare children with and
      without DCD during manual performance were identified following a literature
      search. All were included in the ALE analysis. Compared to controls, children
      with DCD showed reduced activation during a manual dexterity task in the middle
      frontal gyrus, superior frontal gyrus, cerebellum, supramarginal gyrus, and
      inferior parietal lobule. Children with DCD showed greater activation in parts of
      the thalamus. Findings provide much needed clarification into the possible neural
      contributors to atypical manual dexterity in DCD and highlight the need for
      neuroimaging studies to include manual performance outcomes.

PMID- 29339005
TI  - Effects of exercise and enrichment on behaviour in CD-1 mice.
AB  - A host of scholarly work has characterized the positive effects of exercise and
      environmental enrichment on behaviour and cognition in animal studies. The
      purpose of this study was to investigate the uptake and longitudinal impact of
      exercise and enrichment on the behavioural phenotype of male and female CD-1
      mice. CD-1 mice housed in standard (STD) or exercise and enrichment (EE)
      conditions post-weaning were tested in the 3-chamber sociability test, open
      field, and elevated plus maze and exercise activity was monitored throughout the
      enrichment protocol. Male and female EE mice both showed reduced anxiety and
      activity in the open field and elevated plus maze relative to sex-matched STD
      mice. EE altered social behaviours in a sex-specific fashion, with only female EE
      mice showing increased social preference relative to female STD mice and a
      preference for social novelty only present in male EE mice. This sexual
      dimorphism was not observed to be a product of exercise uptake, as CD-1 mice of
      both sexes demonstrated a consistent trend of wheel rotation frequencies. These
      findings suggest the importance of considering variables such as sex and strain
      on experimental design variables in future work on environmental enrichment.

PMID- 29339006
TI  - Food allergy induces alteration in brain inflammatory status and cognitive
      impairments.
AB  - Accumulating evidence supports an increase in emotional and behavioral problems
      in patients with food allergy, but the underlying mechanism remains poorly
      understood. Here we found that in addition to inducing an increase of allergic
      factors in serum, food allergy also increased levels of antigen-specific
      immunoglobulins and mast cell marker in the brain. In particular, food allergy
      increased the number of total microglia and the percentage of active microglia in
      the cerebral cortex and hippocampal CA1 areas, and induced the increase of TNF
      alpha in the cerebral cortex. Importantly, these brain allergic responses were
      associated with behavioral impairments, including motor and learning deficits.
      Taken together, our study provides some evidence for profound effects of food
      allergy on brain functions, and thereby provides scientific basis for a better
      explanation of emotional and behavioral problems among patients with food
      allergy.

PMID- 29339007
TI  - Suicides, homicides, accidents, and undetermined deaths in the U.S. military:
      comparisons to the U.S. population and by military separation status.
AB  - PURPOSE: To compare rates of external causes of mortality among individuals who
      served in the military (before and after separation from the military) to the
      U.S. POPULATION:  METHODS: This retrospective cohort study examined all 3.9
      million service members who served from 2002 to 2007. External cause mortality
      data from 2002 to 2009 were used to calculate standardized mortality ratios.
      Negative binomial regression compared differences in the mortality rates for pre-
      and post-separation. RESULTS: Accident and suicide mortality rates were highest
      among cohort members under 30 years of age, and most of the accident and suicide
      rates for these younger individuals exceeded expectation given the U.S.
      population mortality rates. Military suicide rates began below the expected U.S.
      rate in 2002 but exceeded the U.S. rate by 2009. Accident, homicide, and
      undetermined mortality rates remained below the U.S. rates throughout the study
      period. Mortality rates for all external causes were significantly higher among
      separated individuals compared with those who did not separate. Mortality rates
      for individuals after separation from service decreased over time but remained
      higher than the rates for those who had not separated from service. CONCLUSIONS:
      Higher rates of death for all external causes of mortality after separation
      suggest prevention opportunities. Future research should examine how
      preseparation characteristics and experiences may predict postseparation adverse
      outcomes to inform transition programs.

PMID- 29339008
TI  - Updates on the molecular epidemiology of Enterovirus D68 after installation of
      screening test among acute flaccid paralysis patients in Taiwan.
AB  - In respond to acute flaccid paralysis (AFP) in association with Enterovirus D68
      (EV-D68) infection, Taiwan Centers for Disease Control began to screen EV-D68
      infection among each AFP patient since July 2015 and detected the first case in
      August 2016. This article updated the molecular epidemiology trends of EV-D68
      from the national surveillance data.

PMID- 29339009
TI  - A boy with neck weakness.

PMID- 29339010
TI  - Differences in Abortion Service Delivery in Hostile, Middle-ground, and
      Supportive States in 2014.
AB  - OBJECTIVES: In 2013, the majority of women lived in states considered hostile to
      abortion rights, or states with numerous abortion restrictions. By comparison,
      31% lived in supportive states. This study examined differences in abortion
      service delivery according to the policy climate in which clinics must operate.
      METHODS: Data come from the 2014 Abortion Provider Census, which contains
      information about all known abortion-providing facilities in the United States.
      In addition to number and type of facility, we examine several aspects of
      abortion care: provision of only early medication abortion (EMA-only), whether an
      advanced practice clinician provided abortions, gestational parameters, and
      average charge for procedure. All indicators were examined nationally and
      according to whether the clinic was in a state that was hostile, middle ground,
      or supportive of abortion rights. RESULTS: In 2014, hostile and supportive states
      accounted for the same proportion of all U.S. abortions-44% (each)-although 57%
      of women age 15 to 44 lived in hostile states. Hostile states had one-half as
      many abortion-providing facilities as supportive ones. EMA-only facilities
      accounted for 37% of clinics in supportive states compared with 8% in hostile
      states. Sixty-five percent of clinics in supportive states reported that advanced
      practice clinicians provided abortion care, compared with 3% in hostile states.
      After cost of living adjustments, a first-trimester surgical abortion was most
      expensive in middle-ground states ($470) and least expensive in supportive states
      ($402). CONCLUSIONS: The distribution of abortion services, the type of facility
      in which they are provided, and the amount a facility charges all vary according
      to the abortion policy climate.

PMID- 29339011
TI  - Facilitators and Barriers to Healthy Pregnancy Spacing among Medicaid
      Beneficiaries: Findings from the National Strong Start Initiative.
AB  - BACKGROUND: Closely spaced, unintended pregnancies are common among Medicaid
      beneficiaries and create avoidable risks for women and infants, including preterm
      birth. The Strong Start for Mothers and Newborns Initiative, a program of the
      Center for Medicare and Medicaid Innovation, intended to prevent preterm birth
      through psychosocially based enhanced prenatal care in maternity care homes,
      group prenatal care, and birth centers. Comprehensive care offers the opportunity
      for education and family planning to promote healthy pregnancy spacing. METHODS:
      As of March 30, 2016, there were 42,138 women enrolled in Strong Start and 23,377
      women had given birth. Individual-level data were collected through three
      participant survey instruments and a medical chart review, and approximately one
      half of women who had delivered (n = 10,374) had nonmissing responses on a
      postpartum survey that asked about postpartum family planning. Qualitative case
      studies were conducted annually for the first 3 years of the program and included
      629 interviews with staff and 122 focus groups with 887 Strong Start
      participants. RESULTS: Most programs tried to promote healthy pregnancy spacing
      through family planning education and provision with some success. Group care
      sites in particular established protocols for patient-centered family planning
      education and decision making. Despite program efforts, however, barriers to
      uptake remained. These included state and institutional policies, provider
      knowledge and bias, lack of protocols for timing and content of education, and
      participant issues such as transportation or cultural preferences. CONCLUSIONS:
      The Strong Start initiative introduced a number of successful strategies for
      increasing women's knowledge regarding healthy pregnancy spacing and access to
      family planning. Multiple barriers can impact postpartum Medicaid participants'
      capacity to plan and space pregnancies, and addressing such issues holistically
      is an important strategy for facilitating healthy interpregnancy intervals.

PMID- 29339012
TI  - Patient-Rated Access to Needed Care: Patient-Centered Medical Home Principles
      Intertwined.
AB  - BACKGROUND: Primary care teams can facilitate access to care by helping patients
      to determine whether and when care is needed, and coordinating care across
      multiple clinicians and settings. Appointment availability metrics may or may not
      capture these contributions, but patients' own ratings of their access to care
      provide an important alternative view of access that may be more closely related
      to these key functions of care teams. PROCEDURES: We used a 2015 telephone survey
      of 1,395 women veterans to examine associations between key care team functions
      and patient-rated access to needed care. The care team functions were care
      coordination, in-person communication (between patient and care team), and phone
      communication (timely answers to health questions). We controlled for
      sociodemographics, health status, care settings, and other experience of care
      measures. KEY FINDINGS: Overall, 74% of participants reported always or usually
      being able to see a provider for routine care, and 68% for urgent care. In
      adjusted analyses, phone communication was associated with better ratings of
      access to routine care (odds ratio [OR], 4.31; 95% CI, 2.65-6.98) and urgent care
      (OR, 2.26; 95% CI, 1.23-4.18). Care coordination was also associated with better
      ratings of access to routine care (OR, 1.66; 95% CI, 1.01-2.74) and urgent care
      (OR, 2.26; 95% CI, 1.23-4.18). Associations with in-person communication were not
      significant. CONCLUSIONS: Access, communication, and care coordination are
      interrelated. Approaches to improving access may prove counterproductive if they
      compromise the team's ability to coordinate care, or diminish the team's role as
      a primary point of contact for patients.

PMID- 29339013
TI  - The Use of Telemental Health to Meet the Mental Health Needs of Women Using
      Department of Veterans Affairs Services.
AB  - BACKGROUND: Women veterans are a growing segment of Department of Veterans
      Affairs (VA) users with distinct mental health needs and well-documented barriers
      to care. Telemental health holds much promise for reducing barriers to mental
      health care. We assessed VA stakeholders' perceptions of telemental health's
      appropriateness and potential to address the mental health needs of women veteran
      VA users. METHODS: We conducted semistructured qualitative interviews with 40 key
      leadership and clinical stakeholders at VA medical centers and associated
      outpatient clinics. Transcripts were summarized in a template of key domains
      developed based on the interview guide, and coded for topics relevant to women's
      mental health needs and telehealth services. RESULTS: Telemental health was
      perceived to increase access to mental health care, including same-gender care
      and access to providers with specialized training, especially for rural women and
      those with other limiting circumstances. Respondents saw women veterans as being
      particularly poised to benefit from telemental health, owing to responsibilities
      associated with childcare, spousal care, and elder caregiving. Interviewees
      expressed enthusiasm for telemental health's potential and were eager to expand
      services, including women-only mental health groups. Implementation challenges
      were also noted. CONCLUSIONS: Overall, our stakeholders saw telemental health as
      a good fit for helping to address the perceived needs of women veterans,
      especially in addressing the geographical barriers experienced by rural women and
      those with a limited ability to travel. These findings can help to inform gender
      tailored expansion of telemental health within and outside of the VA.

PMID- 29339015
TI  - Ambicor 2-Piece Inflatable Penile Prosthesis: Who and How?
AB  - BACKGROUND: Currently the Ambicor is the only 2-piece inflatable penile
      prosthesis (IPP) available in the United States. By eliminating the separate
      reservoir, this provides certain advantages for patient and surgeon.
      Nevertheless, it composes a small percentage of all IPPs implanted in the United
      States. AIM: To detail the surgical technique for implantation, describe the
      ideal patient candidates best suited for the Ambicor, and discuss the most common
      and some rare complications with a review of the available published literature
      in combination with our clinical experience. METHODS: A PubMed literature search
      was performed to obtain all peer-reviewed articles published in English
      specifically on the Ambicor 2-piece IPP. We also reviewed our clinical experience
      with the Ambicor during the past 2 decades. RESULTS: The published data remain
      limited, because few articles on the Ambicor have been published in the past 10
      years. Overall complication rates were 2.1% to 9.5%. Patient satisfaction rates
      were 75% to 96.4%, with similar partner satisfaction rates. Relative
      contraindications for implantation include patients with significant penile
      deformities, long narrow phalluses, or short phalluses. STRENGTHS AND
      LIMITATIONS: Despite the limited available published data with short follow-up
      periods, this review provides a comprehensive discussion on the technical aspects
      and relevant perioperative counseling recommended for Ambicor implantation.
      CONCLUSION: The prosthetic urologist should offer the Ambicor 2-piece IPP to
      patients with erectile dysfunction whose non-surgical treatment has failed.
      Certain implanters might want to avoid the blind retropubic reservoir placement
      that occurs with 3-piece IPPs and might not be comfortable with an ectopic
      approach and therefore prefer using a 2-piece device. We believe the ideal
      Ambicor candidate is a patient with a current or future pelvic organ transplant,
      decreased manual dexterity, in need of complete phallic reconstruction, or with
      known extensive prior abdominopelvic surgery. Abdelsayed GA, Levine LA. Ambicor 2
      Piece Inflatable Penile Prosthesis: Who and How? J Sex Med 2018;15:410-415.

PMID- 29339014
TI  - Development of GPC3-Specific Chimeric Antigen Receptor-Engineered Natural Killer
      Cells for the Treatment of Hepatocellular Carcinoma.
AB  - Chimeric antigen receptor (CAR)-modified natural killer (NK) cells represent a
      promising immunotherapeutic modality for cancer treatment. However, their
      potential utilities have not been explored in hepatocellular carcinoma (HCC).
      Glypian-3 (GPC3) is a rational immunotherapeutic target for HCC. In this study,
      we developed GPC3-specific NK cells and explored their potential in the treatment
      of HCC. The NK-92/9.28.z cell line was established by engineering NK-92, a highly
      cytotoxic NK cell line with second-generation GPC3-specific CAR. Exposure of
      GPC3+ HCC cells to this engineered cell line resulted in significant in vitro
      cytotoxicity and cytokine production. In addition, soluble GPC3 and TGF-beta did
      not significantly inhibit the cytotoxicity of NK-92/9.28.z cells in vitro, and no
      significant difference in anti-tumor activities was observed in hypoxic (1%)
      conditions. Potent anti-tumor activities of NK-92/9.28.z cells were observed in
      multiple HCC xenografts with both high and low GPC3 expression, but not in those
      without GPC3 expression. Obvious infiltration of NK-92/9.28.z cells, decreased
      tumor proliferation, and increased tumor apoptosis were observed in the GPC3+ HCC
      xenografts. Similarly, efficient retargeting on primary NK cells was achieved.
      These results justified clinical translation of this GPC3-specific, NK cell-based
      therapeutic as a novel treatment option for patients with GPC3+ HCC.

PMID- 29339016
TI  - Expression of sperm PLCzeta and clinical outcomes of ICSI-AOA in men affected by
      globozoospermia due to DPY19L2 deletion.
AB  - Globozoospermia is characterized by the presence of 100% acrosomeless round
      headed spermatozoa in an ejaculate. Failed fertilization after intracytoplasmic
      sperm injection (ICSI) is commonly reported for globozoospermic couples and can
      be overcome by artificial oocyte activation (AOA). Phospholipase C zeta (PLCzeta)
      is one of the main sperm factors involved in oocyte activation and its low
      expression levels mainly account for fertilization failure. Deletion of the
      DPY19L2 gene is reported as a main genetic cause in over 70% of infertile men
      with globozoospermia. The current study assesses the expression profile of sperm
      PLCzeta at RNA and protein levels in 32 DPY19L2 deletion-mediated globozoospermic
      men and reports corresponding clinical outcomes following ICSI with AOA. The
      expression of PLCzeta relative to GAPDH at RNA (0.78 +/- 0.16 versus 1.65 +/-
      0.24; P = 0.02) and protein (0.39 +/- 0.12 versus 0.83 +/- 0.13; P = 0.01) levels
      in globozoospermic men with DPY19L2 deletion was significantly lower compared
      with fertile men (n = 32). Fertilization rate in globozoospermic couples
      following ICSI-AOA was significantly lower compared with fertile men (53.14 +/-
      5.13% versus 87.64 +/- 2.38%, P < 0.001). However, implantation (26.2%) and
      pregnancy (53.8%) rates were not jeopardized by DPY19L2 deletion in these
      couples.

PMID- 29339017
TI  - Reliability and agreement on embryo assessment: 5 years of an external quality
      control programme.
AB  - An external quality-control programme for morphology-based embryo quality
      assessment, incorporating a standardized embryo grading scheme, was evaluated
      over a period of 5 years to determine levels of inter-observer reliability and
      agreement between practising clinical embryologists at IVF centres and the
      opinions of a panel of experts. Following Guidelines for Reporting Reliability
      and Agreement Studies, the Gwet index and proportion of positive (Ppos) and
      negative agreement were calculated. For embryo morphology assessment, a
      substantial degree of reliability was measured between the centres and the panel
      of experts (Gwet index: 0.76; 95% CI 0.70 to 0.84). The agreement was higher for
      good- versus poor-quality embryos. When multinucleation or vacuoles were
      observed, low levels of reliability were obtained (Ppos: 0.56 and 0.43,
      respectively). In blastocysts, the characteristic that presented the largest
      discrepancy was that related to the inner cell mass. In decisions about the final
      disposition of the embryo, reliability between centre and the panel of experts
      was moderate (Gwet index: 0.51; 95% CI 0.41 to 0.60). In conclusion, the ability
      of clinical embryologists to evaluate the presence of multinucleation and
      vacuoles in the early cleavage embryo, and to determine the category of the inner
      cell mass in blastocysts, needs to be improved.

PMID- 29339018
TI  - Nicotine alleviates chronic stress-induced anxiety and depressive-like behavior
      and hippocampal neuropathology via regulating autophagy signaling.
AB  - Recently, we reported that chronic nicotine significantly improved chronic stress
      induced impairments of cognition and the hippocampal synaptic plasticity in mice,
      however, the underlying mechanism still needs to be explored. In the present
      study, 32 male C57BL/6 mice were divided into four groups: control (CON), stress
      (CUS), stress with chronic nicotine administration (CUS + Nic) and chronic
      nicotine administration (Nic). The anxiety-like behavior and neuropathological
      alteration of DG neurons were examined. Moreover, PC12 cells were examined with
      corticosterone in the presence or absence of nicotine. Both cell viability and
      apoptosis were determined. When treated simultaneously with an unpredictable
      chronic mild stress (CUS), nicotine (0.2 mg/kg/d) attenuated behavioral deficits
      and neuropathological alterations of DG neurons. Moreover, Western blotting
      showed that chronic nicotine also elevated the level of autophagy makers
      including Beclin-1 and LC3 II triggered by CUS. In addition, concomitant
      treatment with nicotine (10 MUM) significantly attenuated the loss of PC12 cell
      viability (p < .01) and apoptosis compared to that of corticosterone treatment
      alone. Besides, chronic nicotine also enhanced the protein and RNA expression
      levels of autophagy makers triggered by corticosterone, such as Beclin-1, LC3 II
      and p62/SQSTM1. However, the above improvements were significantly blocked by
      autophagy inhibitor 3-MA. Importantly, the activation of the PI3K/Akt/mTOR
      signaling was carefully tested to illuminate the effects of chronic nicotine.
      Consequently, chronic nicotine played a role of neuroprotection in either CUS
      mice or corticosterone cells associating with the enhancement of the autophagy
      signaling, which was involved in activating the PI3K/Akt/mTOR signaling.

PMID- 29339019
TI  - Immuno-modulatory functions of the type-3 secretion system and impacts on the
      pulmonary host defense: A role for ExoS of Pseudomonas aeruginosa in cystic
      fibrosis.
AB  - Number of previous reviews had described the structures and the various functions
      of the exotoxins produced by the type-3 secretion system of Pseudomonas
      aeruginosa and their roles in the interactions of this bacterium with host cells.
      In this review, we summarize some relevant data of literature on ExoS, an
      exotoxin from the type-3 secretion system of P. aeruginosa, with a particular
      focus on the role of this toxin in the airways innate response of the host to
      infection by this bacterium, and its implication in the elimination of
      Staphylococcus aureus from the airways of patients with cystic fibrosis.

PMID- 29339021
TI  - Being Andrew Lees.

PMID- 29339020
TI  - Cecile Vogt.

PMID- 29339022
TI  - Exposure assessments for a cross-sectional epidemiologic study of US carbon
      nanotube and nanofiber workers.
AB  - BACKGROUND: Recent animal studies have suggested the potential for wide-ranging
      health effects resulting from exposure to carbon nanotubes and nanofibers
      (CNT/F). To date, no studies in the US have directly examined the relationship
      between occupational exposure and potential human health effects. OBJECTIVES: Our
      goal was to measure CNT/F exposures among US workers with representative job
      types, from non-exposed to highly exposed, for an epidemiologic study relating
      exposure to early biologic effects. METHODS: 108 participants were enrolled from
      12 facilities across the US. Personal, full-shift exposures were assessed based
      on the mass of elemental carbon (EC) at the respirable and inhalable aerosol
      particle size fractions, along with quantitatively characterizing CNT/F and
      estimating particle size via transmission electron microscopy (TEM).
      Additionally, sputum and dermal samples were collected and analyzed to determine
      internal exposures and exposures to the hands/wrists. RESULTS: The mean exposure
      to EC was 1.00 MUg/m3 at the respirable size fraction and 6.22 MUg/m3 at the
      inhalable fraction. Analysis by TEM found a mean exposure of 0.1275 CNT/F
      structures/cm3, generally to agglomerated materials between 2 and 10 MUm.
      Internal exposures to CNT/F via sputum analysis were confirmed in 18% of
      participants while ~70% had positive dermal exposures. CONCLUSIONS: We
      demonstrated the occurrence of a broad range of exposures to CNT/F within 12
      facilities across the US. Analysis of collected sputum indicated internal
      exposures are currently occurring within the workplace. This is an important
      first step in determining if exposures in the workforce have any acute or lasting
      health effects.

PMID- 29339023
TI  - Calculated shape dependence of electromagnetic field in tip-enhanced Raman
      scattering by using a monopole antenna model.
AB  - To evaluate the shape of an Ag tip with regard to tip-enhanced Raman scattering
      (TERS) signal, the enhanced electromagnetic (EM) field and scattering spectrum,
      arising from surface plasmon resonance at the apex of the tip, were calculated
      using a finite-difference time domain (FDTD) method. In the calculated forward
      scattering spectra from the smooth Ag tip, the band appeared within the visible
      region, similar to the experimental results and calculation for a corrugated Ag
      cone. In the FDTD calculation of TERS, the Ag tip acting as a monopole antenna
      was adopted by insertion of a perfect electric conductor between the root of the
      tip and a top boundary surface of the calculation space. As a result, the EM
      field was only enhanced at the apex. The shape dependence i.e. the EM field
      calculated at the apex with various curvatures on the different tapered tips,
      obtained using the monopole antenna model, was different from that simulated
      using a conventional dipole antenna model.

PMID- 29339025
TI  - Electroacoustic verification of frequency modulation systems in cochlear implant
      users.
AB  - INTRODUCTION: The frequency modulation system is a device that helps to improve
      speech perception in noise and is considered the most beneficial approach to
      improve speech recognition in noise in cochlear implant users. According to
      guidelines, there is a need to perform a check before fitting the frequency
      modulation system. Although there are recommendations regarding the behavioral
      tests that should be performed at the fitting of the frequency modulation system
      to cochlear implant users, there are no published recommendations regarding the
      electroacoustic test that should be performed. OBJECTIVE: Perform and determine
      the validity of an electroacoustic verification test for frequency modulation
      systems coupled to different cochlear implant speech processors. METHODS: The
      sample included 40 participants between 5 and 18 year's users of four different
      models of speech processors. For the electroacoustic evaluation, we used the
      Audioscan Verifit device with the HA-1 coupler and the listening check devices
      corresponding to each speech processor model. In cases where the transparency was
      not achieved, a modification was made in the frequency modulation gain adjustment
      and we used the Brazilian version of the "Phrases in Noise Test" to evaluate the
      speech perception in competitive noise. RESULTS: It was observed that there was
      transparency between the frequency modulation system and the cochlear implant in
      85% of the participants evaluated. After adjusting the gain of the frequency
      modulation receiver in the other participants, the devices showed transparency
      when the electroacoustic verification test was repeated. It was also observed
      that patients demonstrated better performance in speech perception in noise after
      a new adjustment, that is, in these cases; the electroacoustic transparency
      caused behavioral transparency. CONCLUSION: The electroacoustic evaluation
      protocol suggested was effective in evaluation of transparency between the
      frequency modulation system and the cochlear implant. Performing the adjustment
      of the speech processor and the frequency modulation system gain are essential
      when fitting this device.

PMID- 29339024
TI  - Nrf2/ARE pathway attenuates oxidative and apoptotic response in human
      osteoarthritis chondrocytes by activating ERK1/2/ELK1-P70S6K-P90RSK signaling
      axis.
AB  - Nrf2, a redox regulated transcription factor, has recently been shown to play a
      role in cartilage integrity but the mechanism remains largely unknown.
      Osteoarthritis (OA) is a multifactorial disease in which focal degradation of
      cartilage occurs. Here, we studied whether Nrf2 exerts chondroprotective effects
      by suppressing the oxidative stress and apoptosis in IL-1beta stimulated human OA
      chondrocytes. Expression of Nrf2 and its target genes HO-1, NQO1 and SOD2 was
      significantly high in OA cartilage compared to normal cartilage and was also
      higher in damaged area compared to smooth area of OA cartilage of the same
      patient. Human chondrocytes treated with IL-1beta resulted in robust Nrf2/ARE
      reporter activity, which was inhibited by pretreatment with antioxidants
      indicating that Nrf2 activity was due to IL-1beta-induced ROS generation. Ectopic
      expression of Nrf2 significantly suppressed the IL-1beta-induced generation of
      ROS while Nrf2 knockdown significantly increased the basal as well as IL-1beta
      induced ROS levels in OA chondrocytes. Further, Nrf2 activation significantly
      inhibited the IL-1beta-induced activation of extrinsic and intrinsic apoptotic
      pathways as determined by inhibition of DNA fragmentation, activation of Caspase
      3,-8,-9, cleavage of PARP, release of cytochrome-c, suppression of mitochondrial
      dysfunction and mitochondrial ROS production in OA chondrocytes. Nrf2 over
      expression in OA chondrocytes increased the expression of anti-apoptotic proteins
      while pro-apoptotic proteins were suppressed. Importantly, Nrf2 over-expression
      activated ERK1/2 and its downstream targets-ELK1, P70S6K and P90RSK and
      suppressed the IL-1beta-induced apoptosis whereas inhibition of ERK1/2 activation
      abrogated the protective effects of Nrf2 in OA chondrocytes. Taken together, our
      data demonstrate that Nrf2 is a stress response protein in OA chondrocytes with
      anti-oxidative and anti-apoptotic function and acts via activation of ERK1/2/ELK1
      P70S6K-P90RSK signaling axis. These activities of Nrf2 make it a promising
      candidate for the development of novel therapies for the management of OA.

PMID- 29339027
TI  - A comparative study of osteopontin and MMP-2 protein expression in peripheral and
      central giant cell granuloma of the jaws.
AB  - INTRODUCTION: Oral peripheral and central giant cell granulomas are lesions with
      little-known etiology and pathogenesis. OBJECTIVE: The aim of this study was to
      compare matrix metalloproteinases-2 and osteopontin protein expression in the
      multinucleated giant cells and mononuclear cells of the peripheral and central
      giant cell granuloma lesions. METHODS: In this retrospective study, the presence
      of matrix metalloproteinases-2 and osteopontin in 37 cases of central giant cell
      granuloma and 37 cases of peripheral giant cell granuloma paraffin blocks were
      assessed by streptavidin-biotin immunohistochemistry. Independent sample t-test,
      Chi-square, Mann-Whitney tests and Spearman's rank correlation coefficient were
      used. RESULTS: The osteopontin was expressed in both multinucleated giant cells
      and mononuclear cells in all cases of peripheral and central giant cells
      granulomas. However, the matrix metalloproteinases-2 expression was positive in
      86.5% of giant cells and it was positive in all of mononuclear cells in
      peripheral giant cells granuloma. In central giant cells granulomas, 91.8% of
      giant cells and all mononuclear cells were positive for matrix metalloproteinases
      2 marker. Percentage and Intensity of staining were significantly higher in
      central than peripheral giant cells lesions, for both markers (p?0.05).
      CONCLUSION: This study showed that the expression of osteopontin in giant cells
      supports the theory of osteolcastic nature of these cells. Also, the presence of
      osteopontin and matrix metalloproteinases-2 in mononuclear cells may indicate the
      monocyte-macrophage origin of these cells, as the differentiation of the
      precursors of the mononuclear stromal monocyte/macrophage to osteoclasts is
      possibly affected by the expression of osteolytic factors. Also, may be
      differences in biological behaviors of these lesions are associated with the
      level of osteopontin and matrix metalloproteinases-2 expression.

PMID- 29339028
TI  - Overexpression of CDC7 in malignant salivary gland tumors correlates with tumor
      differentiation.
AB  - INTRODUCTION: Cell division cycle-7 protein is a serine/threonine kinase that has
      a basic role in cell cycle regulation and is a potential prognostic or
      therapeutic target in some human cancers. OBJECTIVES: This study investigated the
      expression of cell division cycle-7 protein in benign and malignant salivary
      gland tumors and also its correlation with clinicopathologic factors. METHODS:
      Immunohistochemical expression of cell division cycle-7 was evaluated in 46
      cases, including 15 adenoid cystic carcinoma, 12 mucoepidermoid carcinoma, 14
      pleomorphic adenoma, and 5 normal salivary glands. Cell division cycle-7
      expression rate and intensity were compared statistically. RESULTS: The protein
      was expressed in almost all tumors. The intensity and mean of cell division cycle
      7 expression were higher in malignant tumors in comparison with pleomorphic
      adenomas (p=0.000). The protein expression was correlated with tumor grades
      (p=0.000). CONCLUSIONS: The present study demonstrated cell division cycle-7
      overexpression in malignant salivary gland tumors in comparison with pleomorphic
      adenomas, and also a correlation with tumor differentiation. Therefore, this
      protein might be a potential prognostic and therapeutic target for salivary gland
      tumors.

PMID- 29339026
TI  - Tinnitus and sound intolerance: evidence and experience of a Brazilian group.
AB  - INTRODUCTION: Tinnitus and sound intolerance are frequent and subjective
      complaints that may have an impact on a patient's quality of life. OBJECTIVE: To
      present a review of the salient points including concepts, pathophysiology,
      diagnosis and approach of the patient with tinnitus and sensitivity to sounds.
      METHODS: Literature review with bibliographic survey in LILACS, SciELO, Pubmed
      and MEDLINE database. Articles and book chapters on tinnitus and sound
      sensitivity were selected. The several topics were discussed by a group of
      Brazilian professionals and the conclusions were described. RESULTS: The
      prevalence of tinnitus has increased over the years, often associated with
      hearing loss, metabolic factors and inadequate diet. Medical evaluation should be
      performed carefully to guide the request of subsidiary exams. Currently available
      treatments range from medications to the use of sounds with specific
      characteristics and meditation techniques, with variable results. CONCLUSION: A
      review on tinnitus and auditory sensitivity was presented, allowing the reader a
      broad view of the approach to these patients, based on scientific evidence and
      national experience.

PMID- 29339029
TI  - Degree of tinnitus improvement with stapes surgery - a review.
AB  - INTRODUCTION: Otospongiosis is temporal bone osteodystrophy, characterized by
      disordered bone resorption and neoformation in genetically predisposed
      individuals. Clinically, otospongiosis is characterized by progressive conductive
      and/or mixed hearing loss and by tinnitus. OBJECTIVE: A review of the last two
      decades of publications that report the degree of tinnitus improvement with
      stapes surgery. METHODS: 125 articles published in the last 20 years mentioning
      the relationship between otosclerosis and tinnitus. Literature has always shown
      that the hearing improvement after stapes surgery was the main result sought and
      found. However, recent articles has reinforced the need for surgery for the
      tinnitus improvement. The ideal time to assess tinnitus through different scales
      is in the sixth month post-operative. The estimated average hearing improvement
      is 93% and tinnitus is 85.52%. RESULTS: Summaries of 12 articles were reviewed
      which fulfilled the search criteria of the survey, and 8 studies were included in
      the study according the selection criteria. This studies investigating the degree
      of tinnitus improvement with stapes surgery, using different scales as: tinnitus
      functional index, visual analog scale, tinnitus functional index and visual
      analog scale, visual analog scale and "questionnaire asking about tinnitus",
      Newman's method and Tinnitus Score Advocated by the Japan Audiological Society.
      The total of the samples of the evaluated articles was of 254 participants.
      CONCLUSION: We conclude that stapes surgery is effective for the treatment of
      tinnitus (average improvement is 85.52%), and hearing loss (average improvement
      is 93%). When deciding about the surgical indication in patients with
      otosclerosis, the presence and level tinnitus should be considered as well as the
      level of hearing.

PMID- 29339030
TI  - Preoperative insulin therapy as a marker for type 2 diabetes remission in obese
      patients after bariatric surgery.
AB  - BACKGROUND: Obesity not only increases the chances of developing diabetes-one of
      the top causes of death in the United States-but it also results in further
      medical complications. OBJECTIVE: To compare the 6-month and 1-year postoperative
      remission rates of type 2 diabetic (T2D) patients after bariatric surgery based
      on preoperative glycosylated hemoglobin (A1C) stratification and pharmacologic
      therapy: insulin-dependent diabetic (IDD) versus noninsulin-dependent diabetic
      (NIDD). SETTING: Academic hospital, United States. METHODS: We retrospectively
      analyzed a prospectively maintained database of 186 obese patients with a
      diagnosis T2D who had undergone either a sleeve gastrectomy or a Roux-en-Y
      gastric bypass surgery at our hospital. RESULTS: At 6 months (n = 180), patients
      who were stratified by preoperative A1C levels (<6.5; >=6.5 to<8; >=8) had 70.5%,
      51.7%, and 30.0% remission rates (P<.001) and at 1 year (n = 118) patients had
      72.0%, 54.0%, and 42.8% remission rates (P = .053), respectively. When patients
      were substratified by preoperative pharmacologic therapy, IDD and NIDD patients
      had different remission rates within the same A1C level. At 6-months follow-up
      within A1C >=6.5 to<8 (IDD versus NIDD), the remission rate was 23.5% versus
      64.1% (odds ratio [OR]: .173, confidence interval [CI]: .0471, .6308, P = .0079),
      and within A1C >=8 the remission was 24.0% versus 37.5% (OR: .5263, CI: .2115,
      1.3096, P = .1676), respectively. At 1-year follow-up within A1C >=6.5 to<8, the
      remission rate was 30.0% versus 62.9% (OR: .2521, CI: .0529, 1.2019, P = .0838),
      and within A1C >=8 the remission was 31.4% versus 61.9% (OR: .2821, CI: .0908,
      .8762, P = .0286), respectively. Furthermore, when IDD patients were compared
      between A1C >=6.5 to<8 and A1C >=8 the remission rates were nearly identical, and
      for NIDD patients A1C was not significantly associated with remission regardless
      of the level, except at 6 months. CONCLUSION: While a difference was observed
      between overall A1C levels-the lower the A1C level, the higher the remission rate
      IDD patients had lower remission rates than NIDD patients irrespective of A1C
      levels; further, IDD patients performed similarly across A1C levels.

PMID- 29339031
TI  - Resolution of type 2 diabetes after sleeve gastrectomy: a 2-step hypothesis.
AB  - BACKGROUND: Weight loss (WL) and altered gut hormonal levels are involved in
      glucose homeostasis after laparoscopic sleeve gastrectomy (LSG). OBJECTIVES: The
      aim of this study was to evaluate the time-related effects of WL, ghrelin, and
      glucacon-like peptide-1 (GLP-1) plasma concentrations on type 2 diabetes
      resolution after LSG. SETTING: University hospital, Italy. METHODS: Ninety-one
      patients who underwent LSG were investigated. Insulin secretion (insulinogenic
      index [IGI]), insulin resistance, plasma glucose level and percentage glycated
      hemoglobin using the oral glucose tolerance test were assessed before surgery, on
      postoperative day 3, and then at 6, 12, 24, and 36 months after LSG. At the same
      time points, WL, ghrelin, and GLP-1 levels were determined. RESULTS: During
      follow-up, the resolution rate of type 2 diabetes was 9.4%, 42.3%, 71.8%, 81.2%,
      and 91.8%, respectively. Ghrelin plasma concentrations decreased significantly
      after LSG (271.5 +/- 24.5 pg/mL versus 122.4 +/- 23.4 pg/mL, P = .04). GLP-1
      plasma concentrations increased significantly after LSG (1.7 +/- 2.6 pg/mL versus
      2.5 +/- 3.4 pg/mL, P = .04). The percentage of excess weight loss and IGI
      presented a positive linear correlation (r) at all follow-up time points with a
      strong positive correlation at 12 and 24 months. A strong negative correlation
      between ghrelin and IGI was recorded during the first 3 days after LSG (r = -.9).
      GLP-1 and IGI presented a strong positive correlation at day 3 and 6 months
      (i.e., .8 and .8, respectively). CONCLUSION: LSG may affect glucose homeostasis
      by 2 different time-related modes: a first step in which the hormonal changes
      play a predominant role in glucose homeostasis and a second step in which the
      percentage excess weight loss determines the metabolic results.

PMID- 29339032
TI  - The relation between pro-oxidant antioxidant balance and glycolipid profile, 6
      months after gastric bypass surgery.
AB  - BACKGROUND: Morbid obesity is a chronic disease that contributes to increased
      oxidative stress. Gastric bypass surgery is the gold standard method in treating
      co-morbidities. OBJECTIVES: The objective of this study was to evaluate the
      relation between pro-oxidant antioxidant balance (PAB) as one measure of
      oxidative stress and glycolipid profile 6 months after gastric bypass surgery.
      SETTING: Imam Reza Hospital, Mashhad University of Medical Sciences, Mashhad,
      Iran. METHODS: Thirty-five morbidly obese patients with body mass index >=35
      kg/m2 with co-morbidities or <=40 kg/m2 were randomly recruited. The PAB assay
      was used to estimate oxidative stress. Anthropometrics and glycolipid profile
      were collected at recruitment and 6 months after surgery. Statistical analysis
      was performed using SPSS 16 software. RESULTS: The study showed a significant
      postoperative reduction in serum PAB values compared with the baseline (P<.001).
      All anthropometric and several glycolipid parameters significantly reduced after
      surgery (P<.001), while serum high-density lipoprotein cholesterol was
      unaffected. Repeated measures analysis of variance showed that postoperative PAB
      values were affected by gastric bypass surgery (F = 12.51, P = .001). Regression
      analysis demonstrated medication usage controlling co-morbidities (beta^ = -.6, P
      = .002) and fasting blood glucose (beta^ = .41, P = .04) as independent factors
      in predicting PAB values 6 months after surgery. CONCLUSIONS: Gastric bypass
      surgery can reduce PAB values in favor of antioxidants 6 months after the
      operation. Accordingly, fasting blood glucose after gastric bypass surgery can be
      an independent factor in predicting PAB values.

PMID- 29339033
TI  - Helminth Modulation of Lung Inflammation.
AB  - Parasitic helminths must establish chronic infections to complete their life
      cycle and therefore are potent modulators of multiple facets of host physiology.
      Parasitic helminths have coevolved with humans to become arguably master
      selectors of our immune system, whereby they have impacted on the selection of
      genes with beneficial mutations for both host and parasite. While helminth
      infections of humans are a significant health burden, studies have shown that
      helminths or helminth products can alter susceptibility to unrelated infectious
      or inflammatory diseases. This has generated interest in the use of helminth
      infections or molecules as therapeutics. In this review, we focus on the impact
      of helminth infections on pulmonary immunity, especially with regard to
      homeostatic lung function, pulmonary viral and bacterial (co)infections, and
      asthma.

PMID- 29339034
TI  - Extracellular matrix proteins and carcinoembryonic antigen-related cell adhesion
      molecules characterize pancreatic duct fluid exosomes in patients with pancreatic
      cancer.
AB  - BACKGROUND: Exosomes are nanovesicles that have been shown to mediate
      carcinogenesis in pancreatic ductal adenocarcinoma (PDAC). Given the direct
      communication of pancreatic duct fluid with the tumor and its relative
      accessibility, we aimed to determine the feasibility of isolating and
      characterizing exosomes from pancreatic duct fluid. METHODS: Pancreatic duct
      fluid was collected from 26 patients with PDAC (n = 13), intraductal papillary
      mucinous neoplasm (IPMN) (n = 8) and other benign pancreatic diseases (n = 5) at
      resection. Exosomes were isolated by serial ultracentrifugation, proteins were
      identified by mass spectrometry, and their expression was evaluated by
      immunohistochemistry. RESULTS: Exosomes were isolated from all specimens with a
      mean concentration of 5.9 +/- 1 * 108 particles/mL and most frequent size of 138
      +/- 9 nm. Among the top 35 proteins that were significantly associated with PDAC,
      multiple carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) and
      extracellular matrix (ECM) proteins were identified. Interestingly, CEACAM 1/5
      expression by immunohistochemistry was seen only on tumor epithelia whereas
      tenascin C positivity was restricted to stroma, suggesting that both tumor and
      stromal cells contributed to exosomes. CONCLUSION: This is the first study
      showing that exosome isolation is feasible from pancreatic duct fluid, and that
      exosomal proteins may be utilized to diagnose patients with PDAC.

PMID- 29339035
TI  - The effect of dietary carbohydrate on gastroesophageal reflux disease.
AB  - BACKGROUND: Acid changes in gastroesophageal reflux with vary component in the
      food have less been studied, especially carbohydrate. We plan to clarify the
      effect of different carbohydrate density on low esophageal acid and reflux
      symptoms of patients with gastroesophgeal reflux disease. METHODS: Twelve
      patients (52 +/- 12 years old; five female) with gastroesophageal reflux disease
      were recruited for the prospective crossover study. Each patient was invited for
      panendoscope, manometry and 24 h pH monitor. The two formulated liquid meal, test
      meal A: 500 ml liquid meal (containing 84.8 g carbohydrate) and B: same volume
      liquid meal (but 178.8 g carbohydrate) were randomized supplied as lunch or
      dinner. Reflux symptoms were recorded. RESULTS: There are significant statistic
      differences in more Johnson-DeMeester score (p = 0.019), total reflux time (%) (p
      = 0.028), number of reflux periods (p = 0.026) and longest reflux (p = 0.015)
      after high carbohydrate diet than low carbohydrate. Total reflux time and number
      of long reflux periods more than 5 min are significant more after high
      carbohydrate diet. CONCLUSION: More acid reflux symptoms are found after high
      carbohydrate diet. High carbohydrate diet could induce more acid reflux in low
      esophagus and more reflux symptoms in patients with gastroesophageal reflux
      disease.

PMID- 29339036
TI  - A cone-beam computed tomography study of C-shaped root canal systems in
      mandibular second premolars in a Taiwan Chinese subpopulation.
AB  - BACKGROUND/PURPOSE: The purpose of this study is to investigate the prevalence
      and the morphologic characteristics of the radicular groove and root canal system
      in human mandibular second premolars with C-shaped root in a Taiwan Chinese
      subpopulation using cone-beam computed tomographic (CBCT) imaging. METHODS: CBCT
      images of 580 mandibular second premolars were collected from 317 patients. All
      of the mandibular second premolars were examined in serial axial sections to
      identify the presence of any C-shaped root and C-shaped canal systems. The
      morphologic characteristics of mandibular second premolars with C-shaped roots
      were studied by performing measurements of serial axial sections. RESULTS: The
      prevalence rate of mandibular second premolars with a C-shaped root was 3.45%
      (20/580 teeth) and the rate of those with a C-shaped canal system was 2.24%
      (13/580 teeth). It was found that 69% of the radicular grooves were located on
      the lingual half of the root (9/13 teeth) in mandibular second premolars with a C
      shaped canal system. In those teeth with a lingual radicular groove, the main
      canal was toward the buccal side. Frequently, the first C-shaped canal image was
      found at the mid-root level. The deepest part of the radicular groove was located
      at about 2.5 mm apical to the first C-shaped canal image. CONCLUSION: There was a
      2-3% morphologic variation of the mandibular second premolar with a C-shaped root
      canal system among the Taiwan Chinese subpopulation investigated in this study.
      Detailed knowledge of the morphological characteristics of teeth may be valuable
      when choosing clinical treatments.

PMID- 29339037
TI  - Reply to the letters to the editor regarding the elevated body mass index is a
      risk factor associated with possible liver cirrhosis across different etiologies
      of chronic liver disease: Methodological issues.

PMID- 29339038
TI  - Curcumin inhibits TGF-beta1-induced connective tissue growth factor expression
      through the interruption of Smad2 signaling in human gingival fibroblasts.
AB  - BACKGROUND/PURPOSE: Many fibrotic processes are associated with an increased
      level of transforming growth factor-beta1 (TGF-beta1). TGF-beta1 can increase
      synthesis of matrix proteins and enhance secretion of protease inhibitors,
      resulting in matrix accumulation. Connective tissue growth factor (CTGF) is a
      downstream profibrotic effector of TGF-beta1 and is associated with the fibrosis
      in several human organs. Curcumin has been applied to reduce matrix accumulation
      in fibrotic diseases. This study was aimed to evaluate whether curcumin could
      suppress TGF-beta1-induced CTGF expression and its related signaling pathway
      involving in this inhibitory action in primary human gingival fibroblasts.
      METHODS: The differences in CTGF expression among three types of gingival
      overgrowth and normal gingival tissues were assessed by immunohistochemistry.
      Gingival fibroblast viability in cultured media with different concentrations of
      curcumin was studied by MTT assay. The effect of curcumin on TGF-beta1-induced
      CTGF expression in primary human gingival fibroblasts was examined by
      immunoblotting. Moreover, the proteins involved in TGF-beta1 signaling pathways
      including TGF-beta1 receptors and Smad2 were also analyzed by immunoblotting.
      RESULTS: CTGF was highly expressed in fibroblasts, epithelial cells and some of
      endothelial cells, smooth muscle cells, and inflammatory cells in phenytoin
      induced gingival overgrowth tissues rather than in those of hereditary and
      inflammatory gingival overgrowth tissues. Moreover, CTGF expression in the
      epithelial and connective tissue layers was higher in phenytoin-induced gingival
      overgrowth tissues than in normal gingival tissues. Curcumin was nontoxic and
      could reduce TGF-beta1-induced CTGF expression by attenuating the phosphorylation
      and nuclear translocation of Smad2. CONCLUSION: Curcumin can suppress TGF-beta1
      induced CTGF expression through the interruption of Smad2 signaling.

PMID- 29339039
TI  - Sixty years of DNA melting in review: Comment on the review article "DNA melting
      and energetics of the double helix" by Alexander Vologodskii and Maxim D. Frank
      Kamenetskii.

PMID- 29339040
TI  - Effectiveness of workplace diabetes prevention programs: A systematic review of
      the evidence.
AB  - PURPOSE: The primary purpose is to review diabetes workplace interventions and
      the degree to which they improve diabetes-related outcomes in employees diagnosed
      with or at risk for T2DM. METHODS: Three electronic databases and ancestry
      searches were used to identify peer reviewed articles published in English from
      2000 to June 2017. RESULTS: The number of participants represented by the 22
      selected studies, excluding one large outlier, was 4243. On average, the samples
      were 57% female and ethnically diverse. Interventions-healthy eating behaviors,
      physical activity, and/or monitoring and self-managing diabetes and
      cardiovascular risk factors-were delivered in group sessions of fewer than 20
      employees. Programs involved 1-h weekly sessions held during lunch hour or at
      other times during the workday for 12 to 24 weeks. Study outcomes, commonly
      measured at 6 and/or 12 months, were consistently positive. CONCLUSION: The
      literature search uncovered beginning evidence that workplace interventions hold
      promise for preventing diabetes and/or its complications. More rigorous,
      creatively designed, workplace studies, are needed for employees at high-risk for
      developing diabetes. PRACTICE IMPLICATIONS: Implications include the need for
      employer education about the benefits of employer support for such programs and
      attention to motivational strategies so employees will take full advantage of
      programs that are offered.

PMID- 29339042
TI  - Chemotherapy-induced Nausea and Vomiting Prophylaxis in High-dose Melphalan and
      Autologous Stem Cell Transplantation.

PMID- 29339041
TI  - Factors influencing women's perceptions of shared decision making during labor
      and delivery: Results from a large-scale cohort study of first childbirth.
AB  - OBJECTIVE: To examine correlates of shared decision making during labor and
      delivery. METHODS: Data were from a cohort of women who gave birth to their first
      baby in Pennsylvania, 2009-2011 (N = 3006). We used logistic regression models to
      examine the association between labor induction and mode of delivery in relation
      to women's perceptions of shared decision making, and to investigate
      race/ethnicity and SES as potential moderators. RESULTS: Women who were Black and
      who did not have a college degree or private insurance were less likely to report
      high shared decision making, as well as women who underwent labor induction,
      instrumental vaginal or cesarean delivery. Models with interaction terms showed
      that the reduction in odds of shared decision making associated with cesarean
      delivery was greater for Black women than for White women. CONCLUSIONS: Women in
      marginalized social groups were less likely to report shared decision making
      during birth and Black women who delivered by cesarean had particularly low odds
      of shared decision making. PRACTICE IMPLICATIONS: Strategies designed to improve
      the quality of patient-provider communication, information sharing, and shared
      decision making must be attentive to the needs of vulnerable groups to ensure
      that such interventions reduce rather than widen disparities.

PMID- 29339043
TI  - The Relationship Between Red Cell Distribution Width and Cancer-Specific Survival
      in Patients With Renal Cell Carcinoma Treated With Partial and Radical
      Nephrectomy.
AB  - INTRODUCTION: The aim of the study was to evaluate the influence of red cell
      distribution width (RDW) on cancer-specific survival (CSS) in patients who
      undergo nephrectomy for renal cell carcinoma (RCC). PATIENTS AND METHODS: A total
      number of 434 patients with pathologically proven RCC treated with radical or
      partial nephrectomy between 2003 and 2012 were identified in a single tertiary
      academic center. To evaluate the accuracy of RDW for CSS prediction, a receiver
      operating characteristic (ROC) curve was plotted. Patients were divided into 2
      groups, with low and high RDW, according to the optimal cutoff value, which was
      determined according to the ROC curve. The association between groups and CSS was
      analyzed using the Kaplan-Meier method with log-rank testing. The Cox
      proportional hazards regression model was applied to perform univariate and
      multivariate analysis for CSS. RESULTS: Median follow-up was 2146 days. There
      were no differences between subjects with high and low RDW in terms of sex, age,
      body mass index, histological type of tumor, frequency of partial nephrectomy,
      and TNM stage. Patients with high RDW had significantly lower hematocrit,
      hemoglobin level, and red blood cell count. Tumor necrosis and larger tumor size
      were significantly more prevalent in the group of patients with high RDW. CSS was
      significantly lower in patients with RDW >= 13.9% compared with patients with RDW
      < 13.9%. After adjustment for pathological and clinical covariates RDW remained
      an independent predictor for CSS in a multivariable model for CSS. CONCLUSION:
      Our study revealed that the RDW might be an easily obtainable prognostic marker
      in RCC patients treated with nephrectomy.

PMID- 29339044
TI  - The Cardiovascular Toxicity of Abiraterone and Enzalutamide in Prostate Cancer.
AB  - INTRODUCTION: The cardiovascular toxicity related to abiraterone and enzalutamide
      has been previously studied by our group. In this analysis, we aim to update our
      previous findings related to abiraterone and enzalutamide, including the new
      available evidence, both in castration-resistant and hormone-sensitive prostate
      cancer. PATIENTS AND METHODS: Prospective studies were identified by searching
      the MEDLINE/PubMed, Cochrane Library, and ASCO Meeting abstracts. Combined
      relative risks (RRs) and 95% confidence intervals (CIs) were calculated using
      fixed- or random-effects methods. RESULTS: We included 7 articles in this meta
      analysis, covering a total of 8660 patients who were used to evaluate
      cardiovascular toxicity. The use of new hormonal agents was associated with an
      increased risk of all-grade (RR, 1.36; 95% CI, 1.13-1.64; P = .001) and high
      grade (RR, 1.84; 95% CI, 1.21-2.80; P = .004) cardiac toxicity. The use of new
      hormonal agents was also associated with an increased risk of all-grade (RR,
      1.98; 95% CI, 1.62-2.43; P = .001) and high-grade (RR, 2.26; 95% CI, 1.84-2.77; P
      = .004) hypertension compared with the controls. Abiraterone was found to
      significantly increase the risk of both cardiac toxicity and hypertension,
      whereas enzalutamide significantly increases only the risk of hypertension. No
      differences were found based on the dose of prednisone used with abiraterone. The
      major limitation of this study is that data are available only as aggregate, and
      no single-patient information could be analyzed. CONCLUSIONS: Abiraterone and
      enzalutamide significantly increase the incidence and RR of cardiovascular
      toxicity in patients affected by metastatic prostate cancer. Follow-up for the
      onset of treatment-related cardiovascular events should therefore be considered
      in these patients.

PMID- 29339045
TI  - Deficiency of dietary pyridoxine disturbed the intestinal physical barrier
      function of young grass carp (Ctenopharyngodon idella).
AB  - The aim of this study was to assess the effects of dietary pyridoxine (PN)
      deficiency on intestinal antioxidant capacity, cell apoptosis and intercellular
      tight junction in young grass carp (Ctenopharyngodon idella). A total of 540
      young grass carp (231.85 +/- 0.63 g) were fed six diets containing graded levels
      of PN (0.12-7.48 mg/kg diet) for 10 weeks. At the end of the feeding trial, the
      fish were challenged with Aeromonas hydrophila for 2 weeks. The results showed
      that compared with the optimal PN level, PN deficiency (1) increased the contents
      of reactive oxygen species (ROS), malondialdehyde (MDA) and protein carbonyl
      (PC), decreased the activities and mRNA levels of antioxidant enzymes such as
      copper, zinc superoxide dismutase (CuZnSOD), catalase (CAT), glutathione
      peroxidase (GPx), glutathione-S-transferase (GST) and glutathione reductase (GR)
      (P < .05); (2) up-regulated the mRNA levels of cysteinyl aspartic acid-protease-3
      (caspase-3), caspase-7, caspase-8, caspase-9, Bcl-2 associated X protein (Bax),
      apoptotic protease activating factor-1 (Apaf-1) and Fas ligand (FasL), and down
      regulated the mRNA levels of inhibitor of apoptosis proteins (IAP), B-cell
      lymphoma protein-2 (Bcl-2) and myeloid cell leukaemia-1 (Mcl-1) (P < .05); (3)
      down-regulated the mRNA levels of ZO-1, occludin [only in middle intestine (MI)],
      claudin-b, claudin-c, claudin-f, claudin-3c, claudin-7a, claudin-7b and claudin
      11, and up-regulated the mRNA levels of claudin-12 and claudin-15a (P < .05),
      which might be partly linked to Kelch-like-ECH-associated protein 1a (Keap1a)/NF
      E2-related factor 2 (Nrf2), p38 mitogen-activated protein kinase (p38MAPK) and
      myosin light chain kinase (MLCK) signalling in the intestines of fish. However,
      the activities and mRNA levels of MnSOD, the mRNA levels of Keap1b, c-Jun N
      terminal protein kinase (JNK) and claudin-15b in three intestinal segments, and
      the mRNA levels of occludin in the proximal intestine (PI) and distal intestine
      (DI) were not affected by graded levels of PN. These data indicate that PN
      deficiency could disturb the intestinal physical barrier function of fish.
      Additionally, based on the quadratic regression analysis for MDA content and GST
      activity, the dietary PN requirements for young grass carp were estimated as 4.85
      and 5.02 mg/kg diet, respectively.

PMID- 29339046
TI  - Stereotactic body radiation therapy (SBRT) for high-risk prostate cancer: Where
      are we now?
AB  - PURPOSE: Stereotactic body radiation therapy (SBRT) is increasingly being used
      for the management of localized prostate cancer. This trend combined with
      declining use of brachytherapy (BT) has pushed issues and questions regarding the
      use of SBRT to the forefront. A systematic literature review was conducted to
      review the current evidence of biochemical disease-free survival (bDFS) and
      toxicity of SBRT in high-risk (HR) prostate cancer. METHODS AND MATERIALS: A
      search was carried out on the PubMed and Embase databases. Studies were included
      if HR patients were treated using SBRT monotherapy or as a boost and bDFS was
      reported. Selected high-dose-rate (HDR) BT studies including HR patients from
      published reviews were selected to compare with SBRT results. Data from recent
      published phase 3 trials involving HR patients were also compared. RESULTS: Our
      search yielded 8862 articles. Of these, 20 studies with a median follow-up from
      1.6 to 7 years were included in this review. The 5-year bDFS was 81% to 91% in
      monotherapy studies and 90% to 98% in boost studies. For reference, 19 studies
      that reported treating HR patients with HDR monotherapy or boost were selected.
      The 5-year bDFS in HDR monotherapy studies and boost studies was 85% to 93% and
      72% to 93%, respectively. The incidence of late grade 3 genitourinary toxicity
      was 0% to 4.4% and 0% to 2.3% in SBRT monotherapy and SBRT boost studies,
      respectively. CONCLUSION: The evidence for SBRT in HR patients in this review is
      based on observational studies with relatively few patients and short follow-up
      (level III evidence). Based on these data and the principles surrounding
      treatment, SBRT boost should ideally be validated in clinical trials. SBRT
      monotherapy should be used cautiously in highly selected HR patients outside of a
      clinical trial. SUMMARY: Stereotactic body radiation therapy (SBRT) is
      increasingly being used for the management of clinically localized prostate
      cancer. This trend, combined with the decline in the use of brachytherapy, has
      pushed issues and questions regarding the use of SBRT to the forefront. A
      systematic literature review was conducted to establish the current evidence of
      biochemical and toxicity outcomes of SBRT in high-risk prostate cancer.

PMID- 29339047
TI  - The impact of semilateral decubitus position on the dose-volume parameters of the
      heart and lung for left sided breast cancer patients: A comparative dosimetric
      study.
AB  - PURPOSE: When treating breast cancer with radiation therapy, the impact of
      treatment position on heart and lung dose-volume parameters (DVPs) is largely
      dependent on the maximal heart distance (MHD) and central lung distance (CLD). We
      evaluate how much heart and lung sparing can be achieved using the semilateral
      decubitus (SLD) position without and with breath hold compared with the standard
      supine position for left-sided breast cancer patients. A secondary aim was to
      investigate the impact of MHD and CLD on heart and lung DVPs. METHODS AND
      MATERIALS: Thirty-five left-sided breast cancer patients were simulated in
      supine, free breathing SLD, and SLD with breath hold positions. A dosimetry plan
      was developed for each of these and 3 plans were compared for target coverage and
      organs at risk sparing. A correlation between CLD, MHD, and planning target
      volume, and heart and ipsilateral lung DVPs was tested. RESULTS: SLD breath hold
      position showed a significant reduction in percentage of heart receiving >=5 Gy
      (V5Gy), V10Gy, V25Gy, V30Gy, mean dose and maximum dose (P < .001), ipsilateral
      lung V20Gy, and mean dose compared with supine (P < 001) and free breathing SLD
      (P = .003 and .006). There was also a significant reduction in the heart DVPs (P
      < .001) and ipsilateral lung DVPs (P < .001 and .007) with free breathing SLD
      compared with the supine position. SLD with or without breath hold were
      associated with significant reduction in MLD (P < .001) and CLD (P = .030 and
      .003) compared with the supine position. CONCLUSION: Treatment plans for patients
      in the SLD position with or without breath hold for left-sided breast cancer
      patients demonstrated a superior heart and lung sparing compared with the supine
      position due to significant reduction in MHD and CLD. MHD and CLD are important
      simulation factors that affect the heart and lung DVP.

PMID- 29339049
TI  - Genotype and homology analysis of pathogenic and colonization strains of Candida
      albicans from hospitalized neonates.
AB  - BACKGROUND: To detect the genotypes of pathogenic and colonization Candida
      albicans strains and to reveal whether there was a homologous relationship
      between these strains. METHODS: Pathogenic and colonization isolates were
      collected from infants in the NICU of Shenzhen People's Hospital (Shenzhen,
      People's Republic of China). rDNA identification, multilocus sequence typing
      (MLST), and multi-loci variable number tandem repeat analysis (MLVA) were used
      for species confirmation, strain identification, phylogenetic tree clustering,
      and assessment of homology among the pathogenic and colonization strains.
      RESULTS: All 48 isolates belonged to C. albicans species; 12 were collected from
      premature infants with fungal sepsis. These isolates generated 5 sequence types
      (ST1867, ST2551, ST2552, ST2937, and ST2945) and were designated as pathogenic
      strains. The other 36 isolates were collected from the infants without fungal
      infection; 9 sequence types were detected and designated as the colonization
      strains. In the phylogenetic tree, the upper branch consisted of a 4 degrees 
      clade composed of 20 colonization isolates designated to 3 strains, and 4
      pathogenic isolates designated to 1 strain; a 5 degrees  clade composed of 8
      pathogenic isolates designated to 3 strains; and a 4 degrees  clade consisting 1
      pathogenic isolate designated to 1 strain and 4 colonization isolates designated
      to 2 strains. The lower branch consisted of a 3 degrees  clade composed of 6
      colonization isolates designated to 2 strains and a control pathogenic isolate,
      and a 3 degrees  clade composed of 5 colonization isolates designated to 2
      strains. CONCLUSION: Although there was no core ST detected to specify
      pathogenicity or colonization of C. albicans, the genotypes of the colonization
      strains were different from those of the pathogenic strains. Most of the
      colonization and pathogenic strains were highly homologous within their
      classifications while some pathogenic strains had genomes highly homologous with
      those of colonization strains and clustered in heterogeneous groups.

PMID- 29339048
TI  - Intrarenal fat deposition does not interfere with the measurement of single
      kidney perfusion in obese swine using multi-detector computed tomography.
AB  - BACKGROUND: Altered vascular structure or function in several diseases may impair
      renal perfusion. Multi-detector computed tomography (MDCT) is a non-invasive tool
      to assess single-kidney perfusion and function based on dynamic changes in tissue
      attenuation during contrast media transit. However, changes in basal tissue
      attenuation might hamper these assessments, despite background subtraction.
      Evaluation of iodine concentration using the dual-energy (DECT) MDCT mode allows
      excluding effects of basal values on dynamic changes in tissue attenuation. We
      tested whether decreased basal kidney attenuation secondary to intrarenal fat
      deposition in swine obesity interferes with assessment of renal perfusion using
      MDCT. METHODS: Domestic pigs were fed a standard (lean) or a high
      cholesterol/carbohydrate (obese) diet (n = 5 each) for 16 weeks, and both kidneys
      were then imaged using MDCT/DECT after iodinated contrast injection. DECT images
      were post-processed to generate iodine and virtual-non-contrast (VNC) datasets,
      and the MDCT kidney/aorta CT number (following background subtraction) and DECT
      iodine ratios calculated during the peak vascular phase as surrogates of renal
      perfusion. Intrarenal fat was subsequently assessed with Oil-Red-O staining.
      RESULTS: VNC maps in obese pigs revealed decreased basal cortical attenuation,
      and histology confirmed increased renal tissue fat deposition. Nevertheless, the
      kidney/aorta attenuation and iodine ratios remained similar, and unchanged
      compared to lean pigs. CONCLUSIONS: Despite decreased basal attenuation secondary
      to renal adiposity, background subtraction allows adequate assessment of kidney
      perfusion in obese pigs using MDCT. These observations support the feasibility of
      renal perfusion assessment in obese subjects using MDCT.

PMID- 29339050
TI  - Neonatal solid tumors: A therapeutic challenge.

PMID- 29339051
TI  - An unusual GFAP mutation in a Taiwanese child with infantile Alexander disease.

PMID- 29339052
TI  - Neurophysiological effects in cortico-basal ganglia-thalamic circuits of
      antidyskinetic treatment with 5-HT1A receptor biased agonists.
AB  - Recently, the biased and highly selective 5-HT1A agonists, NLX-112, F13714 and
      F15599, have been shown to alleviate dyskinesia in rodent and primate models of
      Parkinson's disease, while marginally interfering with antiparkinsonian effects
      of levodopa. To provide more detailed information on the processes underlying the
      alleviation of dyskinesia, we have here investigated changes in the spectral
      contents of local field potentials in cortico-basal ganglia-thalamic circuits
      following treatment with this novel group of 5-HT1A agonists or the prototypical
      agonist, 8-OH-DPAT. Dyskinetic symptoms were consistently associated with 80 Hz
      oscillations, which were efficaciously suppressed by all 5-HT1A agonists and
      reappeared upon co-administration of the antagonist, WAY100635. At the same time,
      the peak-frequency of fast 130 Hz gamma oscillations and their cross-frequency
      coupling to low-frequency delta oscillations were modified to a different extent
      by each of the 5-HT1A agonists. These findings suggest that the common
      antidyskinetic effects of these drugs may be chiefly attributable to a reversal
      of the brain state characterized by 80 Hz gamma oscillations, whereas the
      differential effects on fast gamma oscillations may reflect differences in
      pharmacological properties that might be of potential relevance for non-motor
      symptoms.

PMID- 29339053
TI  - Upregulation of NLRP3 via STAT3-dependent histone acetylation contributes to
      painful neuropathy induced by bortezomib.
AB  - Painful neuropathy, as a severe side effect of chemotherapeutic bortezomib, is
      the most common reason for treatment discontinuation. However, the mechanism by
      which administration of bortezomib leads to painful neuropathy remains unclear.
      In the present study, we found that application of bortezomib significantly
      increased the expression of NOD-like receptor family pyrin domain containing 3
      (NLRP3) and phosphorylated signal transducer and activator of transcription-3
      (STAT3) in dorsal root ganglion (DRG). Intrathecal injection of NLRP3 siRNA
      significantly prevented the mechanical allodynia induced by bortezomib treatment,
      and intrathecal injection of recombinant adeno-associated virus vector encoding
      NLRP3 markedly decreased paw withdrawal threshold of naive rats. Furthermore, the
      expressions of p-STAT3 were colocalized with NLRP3-positive cells in DRG neurons,
      and inhibition of STAT3 by intrathecal injection of AAV-Cre-GFP into
      STAT3flox/flox mice or inhibitor S3I-201 suppressed the upregulation of NLRP3 and
      mechanical allodynia induced by bortezomib treatment. Chromatin
      immunoprecipitation further found that bortezomib increased the recruitment of
      STAT3, as well as the acetylation of histone H3 and H4, in the NLRP3 promoter
      region in DRG neurons. Importantly, inhibition of the STAT3 activity by using S3I
      201 or DRG local deficiency of STAT3 also significantly prevented the upregulated
      H3 and H4 acetylation in the NLRP3 promoter region following bortezomib
      treatment. Altogether, our results suggest that the upregulation of NLRP3 in DRG
      via STAT3-dependent histone acetylation is critically involved in bortezomib
      induced mechanical allodynia.

PMID- 29339054
TI  - The dynamics of vector-borne relapsing diseases.
AB  - In this paper, we describe the dynamics of a vector-borne relapsing disease, such
      as tick-borne relapsing fever, using the methods of compartmental models. After
      some motivation and model description we provide a proof of a conjectured general
      form of the reproductive ratio R0, which is the average number of new infections
      produced by a single infected individual. A disease free equilibrium undergoes a
      bifurcation at R0=1 and we show that for an arbitrary number of relapses it is a
      transcritical bifurcation with a single branch of endemic equilibria that is
      locally asymptotically stable for R0 sufficiently close to 1. Furthermore, we
      show there is no backwards bifurcation. We then show that these results can be
      extended to variants of the model with an example that allows for variation in
      the number of relapses before recovery. Finally, we discuss implications of our
      results and directions for future research.

PMID- 29339055
TI  - Emotional States and Sudden Death.

PMID- 29339056
TI  - Do Not Resuscitate Tattoos.

PMID- 29339057
TI  - Hidden Giant: Medium Vessel Vasculitis as a Cause for Unresolving Fever.

PMID- 29339058
TI  - Carboxylic group riched graphene oxide based disposable electrochemical
      immunosensor for cancer biomarker detection.
AB  - In this work, we have developed for the first time a carboxylic group riched
      graphene oxide based disposable electrochemical immunosensor for cancer biomarker
      detection using methylene blue (MB). The developed immunosensor is highly
      sensitive for detection of biomarker Mucin1 (MUC1) in human serum samples.
      Development of this disposable electrochemical immunosensor was premeditated by
      applying specific monoclonal antibodies against MUC1. In this method, we explored
      highly conductive surface of carboxylic group (-COOH-) rich graphene oxide (GO)
      on screen-printed carbon electrodes (SPCE). This modified GO-COOH-SPCE was
      employed for the detection of MUC1 protein based on the reaction with methylene
      blue (MB) redox probe using differential pulse voltammetry (DPV) technique.
      Developed immunosensor exhibited good detection range for MUC1 with excellent
      linearity (0.1 U/mL- 2 U/mL), with a limit of detection of 0.04 U/mL. Upon
      potential application of developed biosensor, good recoveries were recorded in
      the range of 96-96.67% with % R.S.D 4.2. Analytical performance of the developed
      immunosensor assures the applicability in clinical diagnostic applications.

PMID- 29339059
TI  - Moving toward rapid and low-cost point-of-care molecular diagnostics with a
      repurposed 3D printer and RPA.
AB  - Traditionally, the majority of nucleic acid amplification-based molecular
      diagnostic tests are done in centralized settings. In recent years, point-of-care
      tests have been developed for use in low-resource settings away from central
      laboratories. While most experts agree that point-of-care molecular tests are
      greatly needed, their availability as cost-effective and easy-to-operate tests
      remains an unmet goal. In this article, we discuss our efforts to develop a
      recombinase polymerase amplification reaction-based test that will meet these
      criteria. First, we describe our efforts in repurposing a low-cost 3D printer as
      a platform that can carry out medium-throughput, rapid, and high-performing
      nucleic acid extraction. Next, we address how these purified templates can be
      rapidly amplified and analyzed using the 3D printer's heated bed or the
      deconstructed, low-cost thermal cycler we have developed. In both approaches,
      real-time isothermal amplification and detection of template DNA or RNA can be
      accomplished using a low-cost portable detector or smartphone camera. Last, we
      demonstrate the capability of our technologies using foodborne pathogens and the
      Zika virus. Our low-cost approach does not employ complicated and high-cost
      components, making it suitable for resource-limited settings. When integrated and
      commercialized, it will offer simple sample-to-answer molecular diagnostics.

PMID- 29339060
TI  - Quantification of a recombinant antigen in an immuno-stimulatory whole yeast cell
      based therapeutic vaccine.
AB  - Therapeutic vaccines represent an emerging class of immune-modulatory treatments
      for cancer, infections, and chronic diseases. One such vaccine was designed as an
      immune stimulator of the T cell response against HBV antigens to eliminate HBV
      infected cells and offer a therapeutic avenue to treat patients suffering from
      chronic hepatitis B infection. Whole deactivated Saccharomyces cerevisiae cells
      expressing a recombinant fusion of HBV X, S and Core antigens elicit T cell
      responses in mice and activate human T cells linked with viral clearance. As the
      therapeutic efficacy of the yeast-based vaccine relies on the production of the
      recombinant antigen, analytical methods designed to accurately and precisely
      quantitate the fusion protein in the midst of all the yeast proteins are
      necessary. We report the development and characterization of western blot,
      quantitative ELISA and mass spectrometry based orthogonal methods to support the
      assessment of manufacturing consistency.

PMID- 29339061
TI  - Dose-dependent photochemical/photothermal toxicity of indocyanine green-based
      therapy on three different cancer cell lines.
AB  - The Food and Drug Administration-approved Indocyanine Green can be used as a
      photosensitizer to kill cancer cells selectively. Although indocyanine green is
      advantageous as a photosensitizer in terms of strong absorption in the near
      infrared region, indocyanine green-based cancer treatment is still not approved
      as a clinical method. Some reasons for this are aggregation at high
      concentrations, rapid clearance of the photosensitizer from the body, low singlet
      oxygen quantum yield, and the uncertainty concerning its action mechanism. This
      in vitro study focuses on two of these points: "what is the cell inhibition
      mechanism of indocyanine green-based therapy?" and "how the dose-dependent
      aggregation problem of indocyanine green alters its cell inhibition efficiency?"
      The following experiments were conducted to provide insight into these points.
      Nontoxic doses of indocyanine green and near-infrared laser were determined. The
      aggregation behavior of indocyanine green was verified through experiments. The
      singlet oxygen quantum yield of indocyanine green at different concentrations
      were calculated. Various indocyanine green and energy densities of near-infrared
      light were applied to prostate cancer, neuroblastoma, and colon cancer cells. An
      MTT assay was performed at the end of the first, second, and third days following
      the treatments to determine the cell viability. Temperature changes in the medium
      during laser exposure were recorded. ROS generation following the treatment was
      verified by using a Total Reactive Oxygen Species detection kit. An apoptosis
      detection test was performed to establish the cell death mechanism and, finally,
      the cellular uptakes of the three different cells were measured. According to the
      results, indocyanine green-based therapy causes cell viability decrease for three
      cancer cell lines by means of excessive reactive oxygen species production.
      Different cells have different sensitivities to the therapy possibly because of
      the differentiation level and structural differences. The singlet oxygen
      generation of indocyanine green decreases at high concentrations because of
      aggregation. Nevertheless, better cancer cell killing effect was observed at
      higher photosensitizer concentrations. This result reveals that the cellular
      uptake of indocyanine green was determinant for better cancer cell inhibition.

PMID- 29339062
TI  - The effect of humeral tunnel locations on radiographic tunnel changes in baseball
      players following medial ulnar collateral ligament reconstruction: comparison of
      anatomic and nonanatomic locations.
AB  - BACKGROUND: There has been no study on radiologic changes after medial ulnar
      collateral ligament (MUCL) reconstruction and related clinical features. METHODS:
      Data from 39 baseball players who underwent MUCL reconstruction were collected
      and analyzed. The baseball players were classified into 2 groups according to the
      starting point of the humeral tunnel: (1) the lower tip of the medial epicondyle
      (group NA, n = 21) and (2) the remnant of the MUCL (group A, n = 18). Bone tunnel
      characteristics and changes were evaluated by computed tomography (CT) at 3 and 9
      months postoperatively. Outcome measures consisted of the visual analog scale,
      range of motion (ROM), the Conway scale, and the presence of ulnar nerve
      irritation postoperatively. RESULTS: The mean diameter of the humeral entry was
      4.0 mm (range, 3.4-5.1 mm) on the first CT scan, which increased to 5.5 mm
      (range, 3.2-7.2 mm) on the follow-up CT scan (P < .001). The mean diameter of the
      ulnar tunnel was 2.8 mm (range, 1.1-3.3 mm) on the first CT scan, which decreased
      to 1.6 mm (range, 0-4.3 mm) on the follow-up CT scan (P < .001). The between
      group comparison revealed no differences in the changes in the diameter of the
      humeral and ulnar tunnels. A statistically significant correlation was not found
      between athletic performance measured by the Conway scale and the radiologic
      changes on CT evaluation (P = .182). Group A showed improvement in extension from
      7 degrees  preoperatively to 1 degrees  postoperatively (P < .001) and in flexion
      from 126 degrees  preoperatively to 136 degrees  postoperatively (P < .001),
      while group NA did not achieve statistical significance in ROM improvement after
      the operation. CONCLUSIONS: Humeral tunnel widening was commonly observed, while
      the ulnar tunnel was maintained or became narrowed conversely. The humeral tunnel
      placements did not affect tunnel changes after the surgical procedure; however,
      MUCL reconstruction with the anatomic location of the humeral tunnel yielded
      substantial improvement in elbow ROM.

PMID- 29339064
TI  - Factors Associated With Early Graft Detachment in Primary Descemet Membrane
      Endothelial Keratoplasty.
AB  - PURPOSE: To evaluate the risk factors for early graft detachment in Descemet
      membrane endothelial keratoplasty (DMEK). DESIGN: Case-control study. METHODS:
      Participants: A total of 173 donor corneas and 173 eyes of the patients following
      DMEK or DMEK in combination with phacoemulsification and intraocular lens
      implantation were included. INTERVENTION: Pre-stripped DMEK grafts were
      transplanted using pull-through technique. At the end of surgery, the anterior
      chamber was filled with air, which was removed 3 hours later only if pupillary
      block was suspected. Rebubbling was performed in all cases with graft detachment,
      independently of its extension, as documented by means of anterior segment
      optical coherence tomography. The donor characteristics were collected from the
      eye bank database and matched with the recipient database. MAIN OUTCOME MEASURES:
      Donor and recipient characteristics affecting graft detachment using univariate
      and multivariate analysis. RESULTS: The combination of DMEK with cataract removal
      and IOL implantation (odds ratio [OR] = 5.31, 95% confidence interval [CI] 2.03
      13.86, P < .002) and air fill of <=75% of anterior chamber height at 2-3 hours
      postoperatively (OR = 2.66, 95% CI 1.12-6.34, P = .027) were found to be
      independent risk factors for postoperative graft detachment. CONCLUSIONS:
      Cataract removal at the time of DMEK is a risk factor for early graft detachment
      and therefore sequential surgery may be preferred over combined surgery in an
      attempt at minimizing rebubbling. Air level in the anterior chamber should be
      monitored and maintained above 75% in the early hours following surgery.

PMID- 29339065
TI  - Accommodative Esotropia Treatment Plan Utilizing Simultaneous Strabismus Surgery
      and Photorefractive Keratectomy.
AB  - PURPOSE: Accommodative esotropia is a common cause of acquired esotropia.
      Pathogenesis varies among patients but usually includes excessive hyperopia and a
      high accommodative convergence/accommodation ratio or tight medial recti. The
      present study reviews an individualized treatment plan combining photorefractive
      keratectomy (PRK) and strabismus surgery to correct these problems. DESIGN: This
      study is a retrospective, interventional case series. METHODS: Records for 15
      patients who were treated for accommodative esotropia were reviewed. Patient ages
      ranged from 11 to 19 years. PRK and strabismus surgery were performed on 11
      patients, and PRK only on 4 patients. The goal was to create a physiologic
      refractive error, good visual acuity (VA), and straight eyes without correction.
      RESULTS: All patients were spectacle free at 6-month follow-up. Twenty-four of 30
      eyes had VA equal to preoperative VA without correction. Three eyes had a 1-line
      reduction and 2-line reduction in VA. The alignment results were +/-10 prism
      diopters in 13 of 15 patients. Spherical refractive outcomes were 18 of 30 eyes
      within 1 diopter (D) of target and 12 of 30 eyes within 2 D of target.
      Astigmatism refractive outcomes were 21 of 30 eyes <1 D, 7 eyes 1-2 D, and 2 eyes
      >2 D. Two patients complained of halos at night, and 1 patient had peripheral
      corneal haze. CONCLUSION: Simultaneous PRK and strabismus surgery is safe and
      effective in treating accommodative esotropia. An individualized treatment plan
      can result in a physiologic refractive error, good VA, and a spectacle-free
      existence.

PMID- 29339063
TI  - Evolution of Intravitreal Therapy for Retinal Diseases-From CMV to CNV: The LXXIV
      Edward Jackson Memorial Lecture.
AB  - PURPOSE: To present the evolution of intravitreal therapy for retinal diseases
      and its impact on clinical practice. DESIGN: Retrospective literature review and
      personal perspective. METHODS: Retrospective literature review and personal
      perspective. RESULTS: Pharmacotherapeutic advances in retinal disease have been
      remarkable over the last 25 years. Almost all of the new drugs developed have
      required intravitreal administration to be highly effective, leading to an
      exponential increase in the annual number of intravitreal injections given. The
      use of intravitreal antibiotic injections to treat endophthalmitis, usually on a
      one-time basis, first familiarized ophthalmologists with this method of drug
      delivery. Ganciclovir was the first widely available, relatively inexpensive
      compounded drug that was used for repeat intravitreal injection to treat a
      chronic retinal disease, followed by triamcinolone for diabetic macular edema and
      bevacizumab for neovascular age-related macular degeneration. Ganciclovir was
      formulated for sustained-release drug delivery to avoid frequent intravitreal
      injections, a goal that has been more elusive for anti-VEGF drugs. Political
      obstacles encountered while conducting some of the trials to evaluate these
      treatments were substantial. Addressing the issues they raised led to important
      national policy changes that will impact the conduct of future clinical trials.
      The first comparative efficacy trial of intravitreal therapies was the Comparison
      of AMD Treatments Trials (CATT). The primary results from CATT and the many
      publications that followed continue to shape the use of intravitreal therapy
      today. CONCLUSION: Intravitreal therapy has proven highly effective for the
      treatment of many retinal diseases. The treatment burden for patients from
      numerous injections, the cost to health care systems, and the impact on workflows
      in clinical practice have been substantial. Efforts to develop effective
      intravitreal therapies with reduced treatment burden and cost are ongoing.

PMID- 29339066
TI  - Apolipoprotein A-I: A favorable prognostic marker in infective endocarditis.
AB  - BACKGROUND: Decreased apolipoprotein A-I (apoA-I) and high-density lipoprotein
      cholesterol (HDL-C) are common in inflammation and sepsis. No study with a large
      sample size has been performed to investigate the prognostic value of apoA-I or
      HDL-C in infective endocarditis (IE). OBJECTIVE: The present study aimed to
      explore the prognostic value of apoA-I and HDL-C for adverse outcomes in IE
      patients. METHODS: Patients with a definite diagnosis of IE between January 2009
      and July 2015 were enrolled and divided into 3 groups according to their apoA-I
      tertiles at admission. Univariate and multivariate analyses were performed to
      evaluate the relationship of apoA-I and HDL-C with clinical outcomes. RESULTS: Of
      the 593 included patients, 40 (6.7%) died in hospital. Patients with lower apoA-I
      experienced markedly higher rates of in-hospital mortality (10.7%, 7.0%, and 2.5%
      in tertiles 1-3, respectively; P = .006) and major adverse clinical events
      (32.5%, 24.1%, and 8.6% in tertiles 1-3, respectively; P < .001). ApoA-I (area
      under the curve, 0.671; P < .001) and HDL-C (area under the curve, 0.672; P <
      .001) had predictive values for in-hospital death. Multivariate logistic
      regression showed that apoA-I <0.90 g/L and HDL-C <0.78 mmol/L were independent
      risk predictors for in-hospital death. A multivariate Cox proportional hazard
      analysis revealed that apoA-I (increments of 1 g/L; hazard ratio, 0.36; 95%
      confidence interval, 0.15-0.87; P = .023) and HDL-C (increments of 1 mmol/L;
      hazard ratio, 0.38; 95% confidence interval, 0.18-0.83; P = .015) were
      independently associated with long-term mortality. CONCLUSIONS: ApoA-I and HDL-C
      were inversely associated with adverse IE prognosis.

PMID- 29339067
TI  - Molecular characterization and function of beta-N-acetylglucosaminidase from
      ridgetail white prawn Exopalaemon carinicauda.
AB  - Chitin degradation is catalyzed by a two-component chitinolytic enzyme system,
      chitinase and beta-N-acetylglucosaminidase (NAGase). In this paper, the full
      length cDNA sequence encoding NAGase (EcNAG) was obtained from Exopalaemon
      carinicauda. The deduced amino acid sequence of EcNAG open reading frame (ORF)
      contained one Glycohydro_20b2 domain and one Glyco_hydro_20 domain. Based on the
      cDNA sequence, the genomic structure of EcNAG was characterized and it was
      composed of six exons and five introns. EcNAG mRNA majorly expressed in the
      hepatopancreas and epidermis. During the molting stages, EcNAG mRNA expression
      was well-regulated and its expression reached the highest level at the molting
      stage E. In addition, EcNAG was recombinant expressed in Pichia pastoris and the
      partial enzymatic characterization of recombinant EcNAG was confirmed. After
      being challenged with Vibrio parahaemolyticus and Aeromonas hydrophila, the
      expression of EcNAG was up-regulated significantly at 6 h and reached the peak at
      12 h. And then, the expression began to down-regulated and came to the normal
      level at 72 h. It is helpful to research the relationship between the molt
      related hormones and chitinlytic enzymes.

PMID- 29339068
TI  - A new miRNA regulator, miR-672, reduces cardiac hypertrophy by inhibiting JUN
      expression.
AB  - Cardiac hypertrophy is one of the initial symptoms of many heart diseases. We
      found that miR-672-5p may participate in the regulation of heart disease
      development in mouse, but the association between miR-672-5p and cardiac
      hypertrophy remains unclear. In the present study, we found that the abundance of
      miR-672-5p decreased in hypertrophic cardiomyocytes induced by phenylephrine,
      angiotensin II (Ang II) and insulin-like growth factor 1. Putative target genes
      of miR-672-5p were identified using four pipelines, miRWalk, miRanda, RNA22 and
      Targetscan, and a total of 834 genes were predicted by all four pipelines. Among
      these target genes, 98 were associated with the development of heart disease. PPI
      networks showed that the Jun proto-oncogene product (JUN), a subunit of the AP-1
      transcription factor, had the highest node degree, and it was defined as the hub
      gene of the PPI networks. Luciferase assays showed that miR-672-5p bound to the
      3' UTR of the JUN gene and decreased luciferase activity, indicating that JUN is
      a target of miR-672-5p. Finally, we found that increasing the abundance of miR
      672-5p in cardiomyocytes controlled the relative cell area in Ang II-stimulated
      hypertrophic cardiomyocytes. Correspondingly, the abundance of JUN, a target of
      miR-672-5p, was decreased in hypertrophic cardiomyocytes on both mRNA and protein
      levels, implying that miR-672-5p had suppressive effects on cardiac hypertrophy
      through regulating the expression of Jun in cardiomyocytes.

PMID- 29339069
TI  - Multiple homologous genes knockout (KO) by CRISPR/Cas9 system in rabbit.
AB  - The CRISPR/Cas9 system is a highly efficient and convenient genome editing tool,
      which has been widely used for single or multiple gene mutation in a variety of
      organisms. Disruption of multiple homologous genes, which have similar DNA
      sequences and gene function, is required for the study of the desired phenotype.
      In this study, to test whether the CRISPR/Cas9 system works on the mutation of
      multiple homologous genes, a single guide RNA (sgRNA) targeting three
      fucosyltransferases encoding genes (FUT1, FUT2 and SEC1) was designed. As
      expected, triple gene mutation of FUT1, FUT2 and SEC1 could be achieved
      simultaneously via a sgRNA mediated CRISPR/Cas9 system. Besides, significantly
      reduced serum fucosyltransferases enzymes activity was also determined in those
      triple gene mutation rabbits. Thus, we provide the first evidence that multiple
      homologous genes knockout (KO) could be achieved efficiently by a sgRNA mediated
      CRISPR/Cas9 system in mammals, which could facilitate the genotype to phenotype
      studies of homologous genes in future.

PMID- 29339070
TI  - Involvement of interferon regulatory factor 3 from the barbel chub Squaliobarbus
      curriculus in the immune response against grass carp reovirus.
AB  - The barbel chub Squaliobarbus curriculus is an important commercial fish species
      in China, and has shown significant resistance to grass carp reovirus (GCRV). In
      this study, the cDNA sequence of interferon regulatory factors 3 (IRF3) from
      Squaliobarbus curriculus, designated as ScIRF3, was cloned, and its effect
      against GCRV was investigated. The full-length 1837 base pair (bp) cDNA of ScIRF3
      contained a complete open reading frame of 1374 bp and encoded a putative
      polypeptide of 457 amino acid residues. The ScIRF3 protein contained conserved
      domains, including an N-terminal DNA-binding domain, a C-terminal IRF association
      domain, and a serine-rich domain. Phylogenetic analysis showed that ScIRF3 was
      closely clustered with IRF3s from Carassius auratus and Ctenopharyngodon idellus.
      Quantitative real-time polymerase chain reaction analysis showed that the
      expression levels of ScIRF3 in Squaliobarbus curriculus were the highest in the
      spleen and lowest in the muscle. After GCRV infection, expression levels of both
      ScIRF3 and type I interferon (IFN) were initially up-regulated and subsequently
      down-regulated in the spleen and intestine. Correlation analysis showed that the
      expression level of type I IFN is significantly positively correlated with that
      of ScIRF3 (Pearson correlation coefficient: 0.883, P: 0.004) in the intestine.
      The expression level of type I IFN was also significantly up-regulated and the
      GCRV titer was significantly decreased (P < .05) in GCRV-infected ScIRF3
      overexpressing Ctenopharyngodon idellus kidney cells. These results indicate that
      ScIRF3 may play a role in the type I IFN immune response against GCRV in
      Squaliobarbus curriculus and can also inhibit GCRV replication in
      Ctenopharyngodon idellus kidney cells.

PMID- 29339071
TI  - MiR-155-5p promotes fibroblast cell proliferation and inhibits FOXO signaling
      pathway in vulvar lichen sclerosis by targeting FOXO3 and CDKN1B.
AB  - Vulvar lichen sclerosis (VLS) is a chronic inflammatory skin disorder. Evidence
      is accumulating that microRNAs (miRNAs) exert crucial roles in initiation and
      development of a wide range of human diseases. MiR-155-5p has been frequently
      reported to be implicated in the tumorigenesis and progression of multiple types
      of cancers, however, its biological role in VLS remains unclear. This study aimed
      to explore the role of miR-155-5p in VLS and clarify the potential molecular
      mechanisms involved. In the present study, miR-155-5p was observed to be
      significantly upregulated in VLS tissues. Functional studies showed that miR-155
      5p facilitated cell proliferation, accelerated cell cycle progression and
      inhibited forkhead box O (FOXO) signaling pathway in fibroblast cells. Mechanical
      studies demonstrated that miR-155-5p exerted its promoting effects on fibroblast
      cell proliferation via targeting both forkhead box O3 (FOXO3) and cyclin
      dependent kinase inhibitor 1B (CDKN1B). Besides, Pearson's correlation analysis
      revealed that miR-155-5p expression was negatively correlated with the mRNA
      expression of FOXO3 and CDKN1B in VLS tissues. Taken together, our results
      indicate that miR-155-5p promotes fibroblast cell proliferation and inhibits FOXO
      signaling pathway by negative modulation of both FOXO3 and CDKN1B in VLS, and
      that miR-155-5p may be used to be a potential therapeutic target for VLS.

PMID- 29339072
TI  - Deep sequencing of a QTL-rich region spanning 128-136Mbp of pig chromosome 15.
AB  - The present study shows the characterization of the chromosome 15 (SSC15) region
      that is highly rich in quantitative traits loci (QTLs) associated with pork
      quality, growth performance, fat and meat carcass contents. The analytic method
      that was utilized included targeted enrichment DNA sequencing and RNA
      hybridisation probes. The research included two pig breeds (Pulawska and Polish
      Landrace) that are significantly different in terms of carcass and meat quality
      features. Filtered sequences were aligned to the Sscrofa10.2 assembly genome with
      the STAR aligner and GATK HaplotypeCaller was used for identified gene variants
      in SSC15 region. In Pulawska pigs, which were characterized by high meat quality,
      mutations were predominantly observed in non-coding regions such as introns and
      intergenic regions. The highest over 50% frequencies of alternate alleles were
      identified in the introns of TNS1, VIL1 and USP37 genes. In the upstream gene
      regions of the Polish Landrace pigs, were observed more mutations than in the
      upstream gene regions of Pulawska. The present study showed interesting gene
      variant panel that could be analyzed in the further association studies in order
      to understand the impact on important productive pig traits.

PMID- 29339073
TI  - The human GCOM1 complex gene interacts with the NMDA receptor and internexin
      alpha.
AB  - The known functions of the human GCOM1 complex hub gene include transcription
      elongation and the intercalated disk of cardiac myocytes. However, in all
      likelihood, the gene's most interesting, and thus far least understood, roles
      will be found in the central nervous system. To investigate the functions of the
      GCOM1 gene in the CNS, we have cloned human and rat brain cDNAs encoding novel,
      105 kDa GCOM1 combined (Gcom) proteins, designated Gcom15, and identified a new
      group of GCOM1 interacting genes, termed Gints, from yeast two-hybrid (Y2H)
      screens. We showed that Gcom15 interacts with the NR1 subunit of the NMDA
      receptor by co-expression in heterologous cells, in which we observed bi
      directional co-immunoprecipitation of human Gcom15 and murine NR1. Our Y2H
      screens revealed 27 novel GCOM1 interacting genes, many of which are synaptic
      proteins and/or play roles in neurologic diseases. Finally, we showed, using rat
      brain protein preparations, that the Gint internexin-alpha (INA), a known
      interactor of the NMDAR, co-IPs with GCOM1 proteins, suggesting a GCOM1-GRIN1-INA
      interaction and a novel pathway that may be relevant to neuroprotection.

PMID- 29339074
TI  - Identification and characterization of a doublesex gene which regulates the
      expression of insulin-like androgenic gland hormone in Fenneropenaeus chinensis.
AB  - The doublesex and its homologue genes are important regulators of sexual
      differentiation which are conserved among animal kingdom. In the present study,
      we reported a doublesex gene (designated as FcDsx) identified from the Chinese
      shrimp F. chinensis. The gene structure, nucleotide and deduced amino acid
      sequences of FcDsx were characterized. The results showed that the deduced amino
      acid sequence of FcDsx had the common features of Dsx proteins, including a
      doublesex/male abnormal 3 (DM) domain, an oligomerization domain and a predicted
      monopartite nuclear localization signal. The expression patterns of FcDsx in
      different tissues and developmental stages were detected. FcDsx exhibited a sex
      biased expression patterns in different tissues and its expression level
      increased along with developmental stages. In addition, its regulation on the
      expression of FcIAG, a gene important for sexual differentiation of male
      crustacean, was also analyzed. Putative Dsx binding site was identified on the
      promoter region of FcIAG and knockdown of FcDsx could reduce the expression of
      FcIAG, which suggested that FcDsx might be the upstream regulator of FcIAG. The
      present data indicated that FcDsx gene might involve in shrimp sexual
      differentiation process.

PMID- 29339075
TI  - Up-regulated lncRNA-MSX2P1 promotes the growth of IL-22-stimulated keratinocytes
      by inhibiting miR-6731-5p and activating S100A7.
AB  - Competitive endogenous RNAs (ceRNAs) regulate RNA transcripts by competing for
      shared miRNAs and play critical roles in disease development. Psoriasis is a long
      lasting, recurring chronic inflammatory skin disease characterized by
      hyperproliferation of keratinocytes. The keratinocyte response is triggered by
      the activation of inflammatory cytokines, like interleukin-22 (IL-22). We used
      lncRNA array analysis to detect differentially expressed lncRNAs in skin (HaCaT)
      cells treated with or without IL-22. We used hematoxylin and eosin (H&E) staining
      to determine the pathological changes in skin cells and immunohistochemistry to
      evaluate the expression of S100A7. We used qRT-PCR and Western blotting to detect
      the expression levels of MSX2P1 and S100A7. We down-regulated the expression of
      MSX2P1 by infecting with lentiviral-vector shRNA. We measured cell proliferation,
      cell cycle status, and apoptosis by the CCK-8 assay, flow cytometry, and Annexin
      V-FITC/PI staining, respectively. In addition, we used the luciferase reporter
      gene assay to determine the relationships between MSX2P1 or miR-6731-5p and
      S100A7, respectively. LncRNA array analysis revealed that 103 lncRNAs were up
      regulated and 51 were down-regulated. Furthermore, qRT-PCR showed that the mRNAs
      levels of MSX2P1 was significantly altered in HaCaT cells treated with IL-22,
      compared with control cells; and MSX2P1 was mainly in the cytoplasm. Based on the
      IL-22-stimulated lncRNA-associated ceRNA network, we selected MSX2P1-miR-6731-5p
      S100A7 for further study. H&E staining exhibited characteristic features specific
      to psoriatic lesions. Immunohistochemistry demonstrated significantly increased
      expression levels of S100A7 in psoriatic lesions, compared with normal skin
      tissue. We observed a positive correlation between lncRNA-MSX2P1 expression and
      S100A7 expression. In addition, miR-6731-5p suppressed proliferation, accelerated
      apoptosis in IL-22-stimulated keratinocytes, and decreased the expressions of
      S100A7, IL-12beta, IL-23, HLA-C, CCHCR1, TNF-alpha, and NF-kappaB proteins. Our
      data demonstrated that MSX2P1 facilitate the progression and growth of IL-22
      stimulated keratinocytes by inhibiting miR-6731-5p and activating S100A7. We
      speculate that the biological network of MSX2P1-miR-6731-5p-S100A7 is a potential
      novel therapeutic target for the future treatment of psoriasis.

PMID- 29339076
TI  - Inhibition of miR-361-5p suppressed pulmonary artery smooth muscle cell survival
      and migration by targeting ABCA1 and inhibiting the JAK2/STAT3 pathway.
AB  - MicroRNAs play a crucial role in the progression of pulmonary arterial
      hypertension (PAH). The aim of this study was to investigate the effect of miR
      361-5p on the proliferation, migration and apoptosis of pulmonary artery smooth
      muscle cells (PASMCs) that under the treatment of hypoxia and explore the
      underlying mechanisms. The results proved that hypoxia noticeably up-regulated
      the expression of miR-361-5p in PASMCs in comparison to the normoxia-treated
      cells, while TNF-alpha and IL-6 stimulation had no obvious effects on miR-361-5p
      level. Hypoxia induced miR-361-5p elevation in a HIF-1alpha-dependent manner.
      Inhibition of miR-361-5p dramatically inhibited hypoxia-induced cell
      proliferation and migration. miR-361-5p inhibition also rescued hypoxia exposure
      caused suppression of PASMCs apoptosis. In addition, the results showed that
      ABCA1 was a direct target of miR-361-5p and was down-regulated in hypoxia-induced
      PASMCs. Hypoxia and TNF-alpha or IL-6 stimulation significantly inhibited ABCA1
      expression. In addition, overexpression of ABCA1 enhanced the effect of miR-361
      5p on hPASMCs. Furthermore, the inhibition of miR-361-5p significantly down
      regulated the expression level of p-JAK2 and p-STAT3. In conclusion, it may
      suggest that the suppression of miR-361-5p suppressed PASMC survival and
      migration by targeting ABCA1 and inhibiting the JAK2/STAT3 pathway.

PMID- 29339077
TI  - How context features modulate the involvement of the working memory system during
      discourse comprehension.
AB  - Using functional magnetic resonance imaging (fMRI), we investigated the effects
      of context features on the involvement of the working memory (WM) system during
      discourse comprehension. During the fMRI scan, participants were asked to read
      two-sentence discourses in which the topic of the second sentence was either
      maintained, or was shifted from, the topic of the first. Changes in the level of
      coherence between the two sentences as well as context length were also
      investigated across discourse items. The WM system was identified with a verbal N
      back task. Analysis of the reading comprehension task revealed that within the WM
      system, stronger activation in the left inferior frontal gyrus corresponded with
      increased bridging coherence demands between sentences, while greater activation
      in the left inferior and middle frontal gyri, bilateral superior frontal gyri,
      and bilateral inferior parietal lobules corresponded with increased context
      length. Topic variation showed no effect on activation of the WM system. These
      results provide new insights into understanding how different levels of context
      features modulate activation of the subcomponents of the WM system and indicate a
      role for the left inferior frontal gyrus as a core component of the WM system
      supporting discourse processing.

PMID- 29339078
TI  - Analytical and pre-analytical performance characteristics of a novel cartridge
      type blood gas analyzer for point-of-care and laboratory testing.
AB  - BACKGROUND: Point-of-care blood gas test results may benefit therapeutic decision
      making by their immediate impact on patient care. We evaluated the (pre
      )analytical performance of a novel cartridge-type blood gas analyzer, the GEM
      Premier 5000 (Werfen), for the determination of pH, partial carbon dioxide
      pressure (pCO2), partial oxygen pressure (pO2), sodium (Na+), potassium (K+),
      chloride (Cl-), ionized calcium (iCa2+), glucose, lactate, and total hemoglobin
      (tHb). METHODS: Total imprecision was estimated according to the CLSI EP5-A2
      protocol. The estimated total error was calculated based on the mean of the range
      claimed by the manufacturer. Based on the CLSI EP9-A2 evaluation protocol, a
      method comparison with the Siemens RapidPoint 500 and Abbott i-STAT CG8+ was
      performed. Obtained data were compared against preset quality specifications.
      Interference of potential pre-analytical confounders on co-oximetry and
      electrolyte concentrations were studied. RESULTS: The analytical performance was
      acceptable for all parameters tested. Method comparison demonstrated good
      agreement to the RapidPoint 500 and i-STAT CG8+, except for some parameters
      (RapidPoint 500: pCO2, K+, lactate and tHb; i-STAT CG8+: pO2, Na+, iCa2+ and tHb)
      for which significant differences between analyzers were recorded. No
      interference of lipemia or methylene blue on CO-oximetry results was found. On
      the contrary, significant interference for benzalkonium and hemolysis on
      electrolyte measurements were found, for which the user is notified by an
      interferent specific flag. CONCLUSION: Identification of sample errors from pre
      analytical sources, such as interferences and automatic corrective actions, along
      with the analytical performance, ease of use and low maintenance time of the
      instrument, makes the evaluated instrument a suitable blood gas analyzer for both
      POCT and laboratory use.

PMID- 29339079
TI  - Diagnostic Usefulness of Combination of Diffusion-weighted Imaging and T2WI,
      Including Apparent Diffusion Coefficient in Breast Lesions: Assessment of
      Histologic Grade.
AB  - PURPOSE: This study aimed to compare the diagnostic values of a combination of
      diffusion-weighted imaging and T2-weighted imaging (DWI-T2WI) with dynamic
      contrast-enhanced magnetic resonance imaging (DCE-MRI), and to evaluate the
      correlation of DWI with the histologic grade in breast cancer. MATERIALS AND
      METHODS: This study evaluated a total of 169 breast lesions from 136 patients who
      underwent both DCE-MRI and DWI (b value, 1000s/mm2). Morphologic and kinetic
      analyses for DCE-MRI were classified according to the Breast Imaging-Reporting
      and Data System. For the DWI-T2WI set, a DWI-T2WI score for lesion
      characterization that compared signal intensity of DWI and T2WI (benign: DWI-T2WI
      score of 1, 2; malignant: DWI-T2WI score of 3, 4, 5) was used. The diagnostic
      values of DCE-MRI, DWI-T2WI set, and combined assessment of DCE and DWI-T2WI were
      calculated. RESULTS: Of 169 breast lesions, 48 were benign and 121 were malignant
      (89 invasive ductal carcinoma, 24 ductal carcinoma in situ, 4 invasive lobular
      carcinoma, 4 mucinous carcinoma). The mean apparent diffusion coefficient (ADC)
      of invasive ductal carcinoma (0.92 +/- 0.19 * 10-3 mm2/s) and ductal carcinoma in
      situ (1.11 +/- 0.13 * 10-3 mm2/s) was significantly lower than the value seen in
      benign lesions (1.36 +/- 0.22 * 10-3 mm2/s). The specificity, positive predictive
      value (PPV), and accuracy of DWI-T2WI set and combined assessment of DCE and DWI
      T2WI (specificity, 87.5% and 91.7%; PPV, 94.3% and 96.2%; accuracy, Az = 0.876
      and 0.922) were significantly higher than those of the DCE-MRI (specificity,
      45.8%; PPV, 81.7%; accuracy, Az = 0.854; P < .05). A low ADC value and the
      presence of rim enhancement were associated with a higher histologic grade cancer
      (P < .05). CONCLUSION: Combining DWI, T2WI, and ADC values provides increased
      accuracy for differentiation between benign and malignant lesions, compared with
      DCE-MRI. A lower ADC value was associated with a higher histologic grade cancer.

PMID- 29339080
TI  - Prostate Cancer Disseminated Tumor Cells are Rarely Detected in the Bone Marrow
      of Patients with Localized Disease Undergoing Radical Prostatectomy across
      Multiple Rare Cell Detection Platforms.
AB  - PURPOSE: Prostate circulating tumor cells escape into peripheral blood and enter
      bone marrow as disseminated tumor cells, representing an early step before
      conventionally detectable metastasis. It is unclear how frequently this occurs in
      localized disease and existing detection methods rely on epithelial markers with
      low specificity and sensitivity. We used multiple methodologies of disseminated
      tumor cell detection in bone marrow harvested at radical prostatectomy. MATERIALS
      AND METHODS: Bone marrow was harvested from 208 clinically localized cases, 16
      controls and 5 metastatic cases with peripheral blood obtained from 37 metastatic
      cases. Samples were evaluated at 4 centers with 4 distinct platforms using
      antibody enrichment with the AdnaTest (Qiagen(r)) or VERSA (versatile exclusion
      based rare sample analysis), or whole sample interrogation with the RareCyte
      platform (Seattle, Washington) or HD-SCA (high definition single cell assay)
      using traditional epithelial markers and prostate specific markers. We
      investigated the sensitivity and specificity of these markers by evaluating
      expression levels in control and metastatic cases. RESULTS: EpCAM, NKX3.1 and AR
      were nonspecifically expressed in controls and in most samples using AdnaTest
      with no relation to perioperative variables. Only 1 patient with localized
      disease showed positive results for the prostate specific marker PSA. With the
      VERSA platform no localized case demonstrated disseminated tumor cells. With the
      RareCyte and HD-SCA platforms only a single patient had 1 disseminated tumor
      cell. CONCLUSIONS: Evaluation across multiple platforms revealed that epithelial
      markers are nonspecific in bone marrow and, thus, not suitable for disseminated
      tumor cell detection. Using prostate specific markers disseminated tumor cells
      were typically not detected in patients with localized prostate cancer.

PMID- 29339081
TI  - Disorder-to-order transitions in the molten globule-like Golgi Reassembly and
      Stacking Protein.
AB  - BACKGROUND: Golgi Reassembly and Stacking Proteins (GRASPs) are widely spread
      among eukaryotic cells (except plants) and are considered as key components in
      both the stacking of the Golgi cisternae and its lateral connection. Furthermore,
      GRASPs were also proved essential in the unconventional secretion pathway of
      several proteins, even though the mechanism remains obscure. It was previously
      observed that the GRASP homologue in Cryptococcus neoformans has a molten globule
      like behavior in solution. METHODS: We used circular dichroism, synchrotron
      radiation circular dichroism and steady-state as well as time-resolved
      fluorescence. RESULTS: We report the disorder-to-order transition propensities
      for a native molten globule-like protein in the presence of different mimetics of
      cell conditions. Changes in the dielectric constant (such as those experienced
      close to the membrane surface) seem to be the major factor in inducing multiple
      disorder-to-order transitions in GRASP, which shows very distinct behavior when
      in conditions that mimic the vicinity of the membrane surface as compared to
      those found when free in solution. Other folding factors such as molecular
      crowding, counter ions, pH and phosphorylation exhibit lower or no effect on
      GRASP secondary structure and/or stability. GENERAL SIGNIFICANCE: To the best of
      our knowledge, this is the first study focusing on understanding the disorder-to
      order transitions of a molten globule structure without the need of any mild
      denaturing condition. A model is also introduced aiming at describing how the
      cell could manipulate the GRASP sensitivity to changes in the dielectric constant
      during different cell-cycle periods.

PMID- 29339082
TI  - Water-mediated interactions enable smooth substrate transport in a bacterial
      efflux pump.
AB  - BACKGROUND: Efflux pumps of the Resistance-Nodulation-cell Division superfamily
      confer multi-drug resistance to Gram-negative bacteria. The most-studied
      polyspecific transporter belonging to this class is the inner-membrane trimeric
      antiporter AcrB of Escherichia coli. In previous studies, a functional rotation
      mechanism was proposed for its functioning, according to which the three monomers
      undergo concerted conformational changes facilitating the extrusion of
      substrates. However, the molecular determinants and the energetics of this
      mechanism still remain unknown, so its feasibility must be proven
      mechanistically. METHODS: A computational protocol able to mimic the functional
      rotation mechanism in AcrB was developed. By using multi-bias molecular dynamics
      simulations we characterized the translocation of the substrate doxorubicin
      driven by conformational changes of the protein. In addition, we estimated for
      the first time the free energy profile associated to this process. RESULTS: We
      provided a molecular view of the process in agreement with experimental data.
      Moreover, we showed that the conformational changes occurring in AcrB enable the
      formation of a layer of structured waters on the internal surface of the
      transport channel. This water layer, in turn, allows for a fairly constant
      hydration of the substrate, facilitating its diffusion over a smooth free energy
      profile. CONCLUSIONS: Our findings reveal a new molecular mechanism of
      polyspecific transport whereby water contributes by screening potentially strong
      substrate-protein interactions. GENERAL SIGNIFICANCE: We provided a mechanistic
      understanding of a fundamental process related to multi-drug transport. Our
      results can help rationalizing the behavior of other polyspecific transporters
      and designing compounds avoiding extrusion or inhibitors of efflux pumps.

PMID- 29339083
TI  - miRNA15a regulates insulin signal transduction in the retinal vasculature.
AB  - We previously reported that tumor necrosis factor alpha (TNFalpha) could inhibit
      insulin signal transduction in retinal cells. We recently found that miR15a/16
      also reduced TNFalpha in retinal endothelial cells (REC) and in vascular specific
      miR15a/16 knockout mice. Since in silico programs suggested that miR15a could
      directly bind the insulin receptor, we wanted to determine whether miR15a altered
      insulin signal transduction. We used a luciferase-based binding assay to
      determine whether miR15a directly bound the insulin receptor. We then used
      Western blotting, ELISA, and qPCR to investigate whether miR15a altered insulin
      signaling proteins in REC and in both miR15a/16 endothelial cell knockout and
      overexpressing mice. We also treated some REC with resveratrol to determine if
      resveratrol could increase miR15a expression, since resveratrol is protective to
      the diabetic retina. We found that miR15a directly bound the 3'UTR of the insulin
      receptor. Treatment with resveratrol increased miR15a expression in REC grown in
      high glucose. While total insulin receptor levels were not altered, insulin
      signal transduction was reduced in REC grown in high glucose and was restored
      with treatment with resveratrol. miR15a knockout mice had reduced insulin
      receptor phosphorylation and Akt2 levels, with increased insulin receptor
      substrate 1 (IRS-1) phosphorylation on serine 307, a site known to inhibit
      insulin signaling. In contrast, overexpression of miR15a increased insulin signal
      transduction. Taken together, these data suggest that miR15a binds the insulin
      receptor and indirectly regulates insulin receptor actions. It also offers an
      additional mechanism by which resveratrol is protective to the diabetic retina.

PMID- 29339084
TI  - miR-613 inhibits cell migration and invasion by downregulating Daam1 in triple
      negative breast cancer.
AB  - Dishevelled-associated activator of morphogenesis 1 (Daam1) is a formin protein
      and participates in regulating cell migration of triple-negative breast cancer
      (TNBC) cells. The specific miRNA targeting Daam1 and mediating cell migration and
      invasion remains obscure. This experiment investigated the suppressive role of
      miR-613 in TNBC cells. The luciferase activity of Daam1 3'-untranslated region
      (3'-UTR) based reporters constructed in HEK-293T and MCF-7 cells suggested that
      Daam1 was the target gene of miR-613. Overexpressed miR-613 reduced the protein
      level of Daam1, weakened RhoA activity, and retarded the cell migration, cell
      invasion and colony formation of TNBC cells. Overexpression of Daam1 or RhoA
      rescued cell migration and invasion in miR-613-overexpressed TNBC cells, but
      failed to reverse colony formation. MiR-613 was significantly downregulated in
      breast cancer tissues compared with that in adjacent normal tissues. This
      downregulation in TNBC tissues and lymphnode metastatic breast cancer tissues was
      more obvious than that in non-TNBC tissues and non-metastatic cancer tissues,
      respectively. MiR-613 weakens the resistance of TNBC cells against paclitaxel
      rather than adriamycin, cyclophosphamide, docetaxel, and kaempferol. Taken
      together, miR-613 is involved in cell migration and invasion of TNBC cells via
      targeting Daam1/RhoA signaling pathway.

PMID- 29339085
TI  - Wnt5a mediates chronic post-thoracotomy pain by regulating non-canonical
      pathways, nerve regeneration, and inflammation in rats.
AB  - As well-characterized ligands involved in neurogenesis, Wnts are emerging as
      promising targets in pain pathogenesis. Our previous pilot study showed that
      intrathecal inhibition of Wnt5a, but not Wnts, relieves chronic post-thoracotomy
      pain (CPTP) in rats. In the present study, we aimed to further explore the
      regulatory mechanism of Wnt5a in CPTP development. Increased protein levels of
      Wnt5a, transmembrane receptor Ror2, and activated non-canonical Wnt pathway
      members were found in the thoracic dorsal root ganglions from postoperative day
      (POD) 7 to POD 21. However, the levels of canonical Wnt pathway members showed no
      change by reverse transcriptase-PCR. In addition, elevated nerve regeneration,
      activated pro-inflammatory factors, and glial cells were detected from POD 7 to
      POD 21. Furthermore, intrathecal Wnt5a blockade during the early phase (POD 0 to
      POD 9) significantly increased the pain threshold, and intervention in the late
      phase (POD 14 to POD 16) alleviated pain; however, the analgesic response was not
      as effective as that in the early phase. Additionally, early but not late Wnt5a
      blockade significantly reversed CPTP-induced activation of the non-canonical Wnt
      pathways, nerve regeneration, and inflammation. In contrast, a Wnt5a agonist
      decreased the pain threshold in both naive and painless rats. These results
      suggest that Wnt5a promotes the development of CPTP by activating non-canonical
      Wnt pathways, nerve regeneration, and inflammation. Therapeutic intervention by
      targeting Wnt5a may represent an effective strategy for preventing and treating
      CPTP.

PMID- 29339086
TI  - The IL-6/STAT3 pathway regulates adhesion molecules and cytoskeleton of
      endothelial cells in thromboangiitis obliterans.
AB  - Thromboangiitis obliterans (TAO) (also known as Buerger's disease) is an
      inflammatory vascular disease that predominantly affects small- and medium-sized
      blood vessels of extremities. Endothelial cells play critical roles in the
      initiation and progression of this disease, but the underlying mechanisms remain
      unclear. In the present study, we demonstrate that patients with TAO had
      significantly higher levels of interleukin-6 (IL-6), soluble intercellular
      adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1
      (sVCAM-1) in their plasmas, and the involved arterial tissues expressed higher
      levels of phosphorylated signal transducer and activator of transcription 3 (p
      STAT3), ICAM-1 and VCAM-1. In exploring the molecular mechanisms with human
      aortic endothelial cells (HAECs), we found that recombinant IL-6 activated the
      STAT3 pathway, leading to the upregulation and overproduction of ICAM-1 and VCAM
      1. RhoA (Ras homolog family member A), eNOS (endothelial nitric oxide synthase)
      and MMP-9 (matrix metalloproteinase-9) participated in this cellular signaling,
      and their interaction regulated the expression of ICAM-1 and VCAM-1. The
      activated STAT3 pathway by IL-6 also modulated the cytoskeleton of HAECs by
      regulating phosphorylation of focal adhesion kinase (FAK) and acetylation of
      alpha-tubulin through interplaying with RhoA. In summary, the present results
      indicate that activation of the IL-6/STAT3 pathway contributes to the
      pathogenesis of TAO by regulating cellular adhesion molecules and cytoskeleton of
      vascular endothelial cells, suggesting that targeting this pathway may provide a
      potential approach for the management of TAO.

PMID- 29339087
TI  - Erratum to: "Spasmodic torticollis after orthognathic surgery" [J. Stomatol. Oral
      Maxillofac. Surg. 118 (2017) 393-6].

PMID- 29339088
TI  - Retinal neuronal cell loss prevents abnormal retinal vascular growth in a rat
      model of retinopathy of prematurity.
AB  - A short-term blockade of the vascular endothelial growth factor (VEGF)-mediated
      pathway in neonatal rats results in formation of severe retinopathy of
      prematurity (ROP)-like retinal blood vessels. The present study aimed to examine
      the role of retinal neurons in the formation of abnormal retinal blood vessels.
      Newborn rats were treated subcutaneously with the VEGF receptor tyrosine kinase
      inhibitor, KRN633 (10 mg/kg), or its vehicle (0.5% methylcellulose in water) on
      postnatal day (P) 7 and P8. To induce excitotoxic loss of retinal neurons, N
      methyl-D-aspartic acid (NMDA) was injected into the vitreous chamber of the eye
      on P9. Changes in retinal morphology, blood vessels, and proliferative status of
      vascular cells were evaluated on P11 and P14. The number of cells in the ganglion
      cell layer and the thickness of the inner plexiform layer and inner nuclear layer
      were significantly decreased 2 days (P11) after NMDA treatment. The pattern and
      degree of NMDA-induced changes in retinal morphology were similar between vehicle
      treated (control) and KRN633-treated (ROP) rats. In ROP rats, increases in the
      density of capillaries, the tortuosity index of arteries, and the proliferating
      vascular cells were observed on P14. The expansion of the endothelial cell
      network was prevented, and the capillary density and the number of proliferating
      cells were reduced in NMDA-treated retinas of both control and ROP rats.
      Following NMDA-induced neuronal cell loss, no ROP-like blood vessels were
      observed in the retinas. These results suggest that retinal neurons play an
      important role in the formation of normal and ROP-like retinal blood vessels.

PMID- 29339089
TI  - Concentration gradient of noradrenaline from the periphery to the centre of the
      cornea - A clue to its origin.
AB  - We set out to demonstrate that the major source of corneal catecholamines is its
      neuronal release from intrinsic sympathetic nerves rather than circulating or non
      neuronal local production. Three concentric segments (central, intermediate,
      peripheral) were obtained by double trephination (9.5-7.25 mm) performed on
      corneas harvested from 3 to 4 month old rabbits and human corneas rejected for
      transplantation, along with aqueous humour, full iris tissue and blood samples.
      Endogenous catecholamines were quantified by high pressure liquid chromatography
      with electrochemical detection (HPLC-ED), and comparison with the uptake of radio
      labelled noradrenaline (3H-NA) before and after incubation with cocaine was
      performed. Results are means +/- SEM. Ratios between enzymatic end products and
      their substrates were calculated. ANOVA was used for statistical analysis.
      Catecholamine levels were found to be about one log unit lower in the human
      cornea than in the rabbit cornea. In the rabbit, dopamine (DA), noradrenaline
      (NA) and adrenaline (AD) were identified by HPLC-ED in all corneal segments,
      whilst in the human cornea NA was identified only in the intermediate and
      peripheral corneal segments, and no AD was found. In the iris and aqueous humour
      only DA and NA were present. A concentration gradient for NA decreasing from the
      periphery to the centre of the cornea was identified in both species (NA/DA ratio
      higher than 1 in the periphery; low AD/NA ratio in all corneal segments), but not
      for DA or AD. After incubation with 3H-NA all corneal segments and iris tissue
      showed loading with the aforementioned gradient being reproduced, and a decrease
      in 3H-NA loading after cocaine was significant only in the peripheral corneal
      segment and in the iris of both species. Reduction in 3H-NA loading after
      incubation with cocaine shows that NA in the cornea is mostly of neuronal origin
      and demonstrates the presence of functional sympathetic nerves (also expectedly
      found in the iris); the existence of a gradient both for 3H-NA loading and
      loading reduction after cocaine points to a higher density of fibres in the
      peripheral cornea.

PMID- 29339090
TI  - Patched 1 Expression Correlates with Biochemical Relapse in High-Risk Prostate
      Cancer Patients.
AB  - There is an unmet clinical need for adequate biomarkers to aid risk
      stratification and management of prostate cancer (PCa) patients. Even within the
      high-risk PCa category, not all patients will invariably have a poor prognosis,
      and improved stratification of this heterogeneous group is needed. In this
      context, components of the hedgehog (Hh) pathway may have promise as biomarkers,
      because the available evidence suggests increased Hh pathway activity may confer
      a poorer outcome in advanced and castrate-resistant PCa. In this study, potential
      associations between Hh pathway protein expression and clinicopathological
      factors, including time to biochemical recurrence (BCR), were investigated using
      a tissue microarray constructed from benign and malignant prostate samples from
      75 predominantly high-risk PCa patients who underwent radical prostatectomy. Hh
      signaling activity was found to differ between benign and malignant prostate
      tissue, with a greater amount of active Hh signaling present in malignant than
      benign prostate epithelium. High expression of Patched 1 in malignant prostate
      epithelium was found to be an independent predictor of BCR in high-risk PCa
      patients. Glioma-associated oncogene 1 may potentially represent a clinically
      useful biomarker of an aggressive tumor phenotype. Evaluation of Hh signaling
      activity in PCa patients may be useful for risk stratification, and epithelial
      Patched 1 expression, in particular, may be a prognostic marker for BCR in high
      risk PCa patients.

PMID- 29339092
TI  - Structural and biochemical analyses reveal ubiquitin C-terminal hydrolase-L1 as a
      specific client of the peroxiredoxin II chaperone.
AB  - Peroxiredoxins (Prxs) play dual roles as both thiol-peroxidases and molecular
      chaperones. Peroxidase activity enables various intracellular functions, however,
      the physiological roles of Prxs as chaperones are not well established. To study
      the chaperoning function of Prx, we previously sought to identify heat-induced
      Prx-binding proteins as the clients of a Prx chaperone. By using His-tagged Prx I
      as a bait, we separated ubiquitin C-terminal hydrolase-L1 (UCH-L1) as a heat
      induced Prx I binding protein from rat brain crude extracts. Protein complex
      immunoprecipitation with HeLa cell lysates revealed that both Prx I and Prx II
      interact with UCH-L1. However, Prx II interacted considerably more favorably with
      UCH-L1 than Prx I. Prx II exhibited more effective molecular chaperone activity
      than Prx I when UCH-L1 was the client. Prx II interacted with UCH-L1 through its
      C-terminal region to protect UCH-L1 from thermal or oxidative inactivation. We
      found that chaperoning via interaction through C-terminal region (specific-client
      chaperoning) is more efficient than that involving oligomeric structural change
      (general-client chaperoning). Prx II binds either thermally or oxidatively
      unfolding early intermediates of specific clients and thereby shifted the
      equilibrium towards their native state. We conclude that this chaperoning
      mechanism provides a very effective and selective chaperoning activity.

PMID- 29339093
TI  - The proteoglycan biglycan mediates inflammatory response by activating TLR-4 in
      human chondrocytes: Inhibition by specific siRNA and high polymerized Hyaluronan.
AB  - Cartilage degeneration are hallmarks of wear, tear, mechanical and inflammatory
      damage of the joint cartilage. Tissue degradation as well as compromising the
      integrity and function of the organ, produces different intermediates, directly
      able to stimulate further inflammatory effect, therefore, amplifying the
      inflammation response. Biglycan is a soluble component of the extracellular
      matrix that is released during tissue injury. It has been reported that released
      biglycan is an endogenous ligand for TLR-2/4 in some cell type. We studied the
      role of biglycan in an experimental model of biglycan-induced inflammatory
      response in human chondrocytes and the effect of high polymerized HA on reducing
      its activity. Exposition of chondrocytes to LPS generated cell injury, including
      high levels of biglycan. Chondrocyte treatment with biglycan produces a high mRNA
      expression of several detrimental inflammation mediators such as IL-1beta, IL-6,
      MMP-13, and IL-17, as well as NF-kB and TLR-4 activation. Administration of high
      polymerized HA to chondrocytes exposed to biglycan was able to attenuate the
      inflammatory response by decreasing the expression of the inflammatory mediators.
      Involvement of the TLR-4 in the mediation of the biglycan action was confirmed
      using a specific silent agent (siRNA). Taken together, these data could be used
      to develop new anti-inflammatory approaches.

PMID- 29339095
TI  - Patterning the gastrointestinal epithelium to confer regional-specific functions.
AB  - The gastrointestinal (GI) tract, in simplest terms, can be described as an
      epithelial-lined muscular tube extending along the cephalocaudal axis from the
      oral cavity to the anus. Although the general architecture of the GI tract organs
      is conserved from end to end, the presence of different epithelial tissue
      structures and unique epithelial cell types within each organ enables each to
      perform the distinct digestive functions required for efficient nutrient
      assimilation. Spatiotemporal regulation of signaling pathways and downstream
      transcription factors controls GI epithelial morphogenesis during development to
      confer essential regional-specific epithelial structures and functions. Here, we
      discuss the fundamental functions of each GI tract organ and summarize the
      diversity of epithelial structures present along the cephalocaudal axis of the GI
      tract. Next, we discuss findings, primarily from genetic mouse models, that have
      defined the roles of key transcription factors during epithelial morphogenesis,
      including p63, SOX2, SOX15, GATA4, GATA6, HNF4A, and HNF4G. Additionally, we
      examine how the Hedgehog, WNT, and BMP signaling pathways contribute to defining
      unique epithelial features along the cephalocaudal axis of the GI tract. Lastly,
      we examine the molecular mechanisms controlling regionalized cytodifferentiation
      of organ-specific epithelial cell types within the GI tract, concentrating on the
      stomach and small intestine. The delineation of GI epithelial patterning
      mechanisms in mice has provided fundamental knowledge to guide the development
      and refinement of three-dimensional GI organotypic culture models such as those
      derived from directed differentiation of human pluripotent stem cells and those
      derived directly from human tissue samples. Continued examination of these
      pathways will undoubtedly provide vital insights into the mechanisms of GI
      development and disease and may afford new avenues for innovative tissue
      engineering and personalized medicine approaches to treating GI diseases.

PMID- 29339096
TI  - A new option for remission induction in acute myeloid leukaemia.

PMID- 29339091
TI  - An energetic view of stress: Focus on mitochondria.
AB  - Energy is required to sustain life and enable stress adaptation. At the cellular
      level, energy is largely derived from mitochondria - unique multifunctional
      organelles with their own genome. Four main elements connect mitochondria to
      stress: (1) Energy is required at the molecular, (epi)genetic, cellular,
      organellar, and systemic levels to sustain components of stress responses; (2)
      Glucocorticoids and other steroid hormones are produced and metabolized by
      mitochondria; (3) Reciprocally, mitochondria respond to neuroendocrine and
      metabolic stress mediators; and (4) Experimentally manipulating mitochondrial
      functions alters physiological and behavioral responses to psychological stress.
      Thus, mitochondria are endocrine organelles that provide both the energy and
      signals that enable and direct stress adaptation. Neural circuits regulating
      social behavior - as well as psychopathological processes - are also influenced
      by mitochondrial energetics. An integrative view of stress as an energy-driven
      process opens new opportunities to study mechanisms of adaptation and regulation
      across the lifespan.

PMID- 29339097
TI  - Safety and preliminary efficacy of venetoclax with decitabine or azacitidine in
      elderly patients with previously untreated acute myeloid leukaemia: a non
      randomised, open-label, phase 1b study.
AB  - BACKGROUND: Elderly patients (aged >=65 years) with acute myeloid leukaemia have
      poor outcomes and no effective standard-of-care therapy exists. Treatment with
      hypomethylating agents such as azacitidine and decitabine is common, but
      responses are modest and typically short-lived. The oral anti-apoptotic B-cell
      lymphoma 2 protein inhibitor, venetoclax, has shown promising single-agent
      activity in patients with relapsed or refractory acute myeloid leukaemia and
      preclinical data suggested synergy between hypomethylating agents and venetoclax,
      which led to this combination phase 1b study. METHODS: Previously untreated
      patients aged 65 years and over with acute myeloid leukaemia who were ineligible
      for standard induction therapy were enrolled into this non-randomised, open
      label, phase 1b study. Patients were required to have an Eastern Cooperative
      Oncology Group performance status of 0-2 and either intermediate-risk or poor
      risk cytogenetics. Patients were enrolled into one of three groups for the dose
      escalation phase of this study: group A (venetoclax and intravenous decitabine 20
      mg/m2 [days 1-5 of each 28-day cycle]), group B (venetoclax and subcutaneous or
      intravenous azacitidine 75 mg/m2 [days 1-7 of each 28-day cycle]), and group C (a
      venetoclax and decitabine substudy with the oral CYP3A inhibitor posaconazole,
      300 mg twice on cycle 1, day 21, and 300 mg once daily from cycle 1, days 22-28,
      to assess its effect on venetoclax pharmacokinetics). Dose escalation followed a
      standard 3 + 3 design with at least three evaluable patients enrolled per cohort;
      daily target doses of venetoclax for groups A and B were 400 mg (cohort 1), 800
      mg (cohorts 2 and 3), and 1200 mg (cohort 4), and 400 mg for group C. The primary
      endpoints were the safety and pharmacokinetics of venetoclax plus decitabine or
      azacitidine, and to determine the maximum tolerated dose and recommended phase 2
      dose. Secondary endpoints included the preliminary anti-leukaemic activity of
      venetoclax with decitabine or azacitidine through the analysis of overall
      response, duration of response, and overall survival. We analysed safety,
      pharmacokinetics, and anti-leukaemic activity in all patients who received one or
      more venetoclax doses. The expansion phase of the study is ongoing but is closed
      to accrual. This trial is registered with ClinicalTrials.gov, number NCT02203773.
      FINDINGS: 57 patients were enrolled in the study. 23 patients in group A and 22
      patients in group B were enrolled between Nov 19, 2014, and Dec 15, 2015, and 12
      patients in group C were enrolled between June 14, 2015, and Jan 16, 2016. As of
      data cutoff on June 15, 2016, the most common grade 3-4 treatment-emergent
      adverse events were thrombocytopenia (27 [47%] of 57 patients; nine in group A,
      13 in group B, and five in group C), febrile neutropenia (24 [42%] of 57; 11 in
      group A, ten in group B, and three in group C), and neutropenia (23 [40%] of 57;
      12 in group A, eight in group B, and three in group C). The most common serious
      treatment-emergent adverse event in groups A and B was febrile neutropenia (seven
      [30%] of 23 patients vs seven [32%] of 22), whereas in group C it was lung
      infection (four [33%] of 12 patients). 49 (86%) of 57 patients had treatment
      related adverse events; the most common in groups A and B included nausea (12
      [52%] patients vs seven [32%] patients), fatigue (six [26%] patients vs seven
      [32%]), and decreased neutrophil count (six [26%] patients vs six [27%]), whereas
      in group C the most common were nausea (seven [58%] of 12 patients), leucopenia
      (six [50%]), vomiting (five [42%]), and decreased platelet count (five [42%]).
      The maximum tolerated dose was not reached. The recommended phase 2 dose was 400
      mg once a day or 800 mg with an interrupted dosing schedule (safety expansion).
      In total, four (7%) of 57 patients had died within 30 days of the first
      venetoclax dose caused by sepsis (group B), bacteraemia (group A), lung infection
      (group C), and respiratory failure (group A). Tumour lysis syndrome was not
      observed. Decitabine and azacitidine did not substantially affect venetoclax
      exposures. Overall, 35 (61%; 95% CI 47.6-74.0) of 57 patients achieved complete
      remission or complete remission with incomplete marrow recovery. In groups A and
      B, 27 (60%; 95% CI 44.3-74.3) of 45 patients had complete remission or complete
      remission with incomplete marrow recovery. INTERPRETATION: Venetoclax plus
      hypomethylating agent therapy seems to be a novel, well-tolerated regimen with
      promising activity in this underserved patient population. Evaluation of
      expansion cohorts is ongoing at 400 mg and 800 mg doses using both
      hypomethylating agent combinations. FUNDING: AbbVie and Genentech.

PMID- 29339098
TI  - Vitamin D and Nonalcoholic Fatty Liver Disease: Bi-directional Mendelian
      Randomization Analysis.
AB  - BACKGROUND: Vitamin D deficiency is associated with nonalcoholic fatty liver
      disease (NAFLD) in many cross-sectional studies. However, the causality between
      them has not been established. We used bi-directional mendelian randomization
      (MR) analysis to explore the causal relationship between 25-hydroxyvitamin D
      [25(OH)D] and NAFLD. METHODS: 9182 participants were included from a survey in
      East China from 2014 to 2016. We calculated weighted genetic risk scores (GRS)
      for 25(OH)D concentration and NAFLD based on 25(OH)D-related and NAFLD-related
      single nucleotide polymorphisms. Presence of liver steatosis was assessed using
      ultrasound. Instrumental variable was used to measure the causal relationship
      between them. RESULTS: An SD increase in the 25(OH)D GRS was significantly
      associated with 25(OH)D (beta 1.29, 95%CI -1.54, -1.04, P<0.05) but not with
      NAFLD (OR 0.97, 95%CI 0.92, 1.01). An SD increase in NAFLD GRS was also strongly
      associated with NAFLD (OR 1.09, 95%CI 1.04, 1.15, P<0.05) but not with 25(OH)D
      (beta -0.15, 95%CI -0.41, 0.10). Using an instrumental variable estimator, no
      associations were found for genetically instrumented 25(OH)D with NAFLD and for
      genetically instrumented NAFLD with 25(OH)D. CONCLUSION: Our results support the
      conclusion that there is no causal association between vitamin D and NAFLD using
      a bi-directional MR approach in a Chinese population.

PMID- 29339099
TI  - Intestinal Adenovirus Shedding Before Allogeneic Stem Cell Transplantation Is a
      Risk Factor for Invasive Infection Post-transplant.
AB  - Human adenoviruses (HAdV) are a major cause of morbidity and mortality in
      pediatric human stem cell transplant (HSCT) recipients. Our previous studies
      identified the gastrointestinal tract as a site of HAdV persistence, but the role
      of intestinal virus shedding pre-transplant for the risk of ensuing invasive
      infection has not been entirely elucidated. Molecular HAdV monitoring of serial
      stool samples using RQ-PCR was performed in 304 children undergoing allogeneic
      HSCT. Analysis of stool and peripheral blood specimens was performed pre
      transplant and at short intervals until day 100 post-HSCT. The virus was detected
      in the stool of 129 patients (42%), and 42 tested positive already before HSCT.
      The patients displaying HAdV shedding pre-transplant showed a significantly
      earlier increase of intestinal HAdV levels above the critical threshold
      associated with high risk of invasive infection (p<0.01). In this subset of
      patients, the occurrence of invasive infection characterized by viremia was
      significantly higher than in patients without HAdV shedding before HSCT (33% vs
      7%; p<0.0001). The data demonstrate that intestinal HAdV shedding before HSCT
      confers a greatly increased risk for invasive infection and disseminated disease
      post-transplant, and highlights the need for timely HAdV monitoring and pre
      emptive therapeutic considerations in HSCT recipients.

PMID- 29339100
TI  - Genetic Variation in the Dopamine System Influences Intervention Outcome in
      Children with Cerebral Palsy.
AB  - BACKGROUND: There is large variation in treatment responses in children with
      cerebral palsy. Experimental and clinical results suggest that dopamine
      neurotransmission and brain-derived neurotrophic factor (BDNF) signalling are
      involved in motor learning and plasticity, which are key factors in modern
      habilitation success. We examined whether naturally occurring variations in
      dopamine and BDNF genes influenced the treatment outcomes. METHODS: Thirty-three
      children (18-60months of age) with spastic unilateral cerebral palsy were
      enrolled in the study. Each child had participated in a training programme
      consisting of active training of the involved hand for 2h every day during a 2
      month training period. The training outcome was measured using Assisting Hand
      Assessment before and after the training period. Saliva was collected for
      genotyping of COMT, DAT, DRD1, DRD2, DRD3, and BDNF. Regression analyses were
      used to examine associations between genetic variation and training outcome.
      FINDINGS: There was a statistically significant association between variation in
      dopamine genes and treatment outcome. Children with a high polygenic dopamine
      gene score including polymorphisms of five dopamine genes (COMT, DAT, DRD1, DRD2,
      and DRD3), and reflecting higher endogenous dopaminergic neurotransmission, had
      the greatest functional outcome gains after intervention. INTERPRETATION:
      Naturally occurring genetic variation in the dopamine system can influence
      treatment outcomes in children with cerebral palsy. A polygenic dopamine score
      might be valid for treatment outcome prediction and for designing individually
      tailored interventions for children with cerebral palsy.

PMID- 29339101
TI  - Atherogenic diet induced lipid accumulation induced NFkappaB level in heart,
      liver and brain of Wistar rat and diosgenin as an anti-inflammatory agent.
AB  - Atherogenic Diet (AD) was given to rats to understand the key role of
      inflammatory mediators in atherosclerotic lesion formation, as a serendipitous
      study, the diet induced inflammatory mediators in liver and brain, whereas
      pancreas, kidney and spleen were not affected. The efficacy of diosgenin in
      ameliorating atherosclerotic progression in heart and suppression of inflammatory
      mediators in liver and brain of Wistar rat fed on AD diet was investigated.
      Atherogenic diet triggered inflammatory mediators in heart, liver and brain by
      upregulating TNF-alpha, COX-2 and NFkBp65 which are the inflammatory hub, played
      a key role in pathophysiologic conditions. Endothelial dysfunction, liver tissue
      with prominent steatosis and the stress evoked in the brain by the atherogenic
      diet triggered these inflammatory mediators. TNF-alpha and COX-2 expression was
      upregulated and its elevation was associated with NFkBp65 activation in heart,
      liver and brain of atherogenic diet induced rat. Diosgenin downregulated these
      inflammatory mediators, thereby prevented the atherosclerotic disease progression
      and concomitant suppression of inflammatory mediators in liver and brain.

PMID- 29339102
TI  - Spirulina ameliorates methotrexate hepatotoxicity via antioxidant, immune
      stimulation, and proinflammatory cytokines and apoptotic proteins modulation.
AB  - AIMS: Methotrexate (MTX) is an efficient cytotoxic drug used against various
      carcinogenic, inflammatory and autoimmune diseases; however, the hepatotoxicity
      of MTX limits its use. Therefore, the present study aimed to evaluate the
      potential hepatoprotective and immune-stimulant effect of Spirulina platensis
      (SP) against MTX acute toxicity. MAIN METHODS: Thirty-two male Wistar rats were
      randomly allocated into the following four groups (n = 8): control, SP (500 mg/kg
      bwt, oral gavage daily for 21 days), MTX (20 mg/kg bwt, single ip injection), and
      MTX+SP. Hepatic and splenic histoarchitecture, leukocyte counts and serum
      immunoglobulins were evaluated. Hepatic oxidant/antioxidant status,
      proinflammatory cytokines (tumor necrosis factor-alpha, and interleukin 6), and
      pro-apoptotic proteins (caspase 3 and Bax) immunoexpression were assessed. KEY
      FINDINGS: MTX induced extensive hepatic necrosis and vacuolation, and sever
      lymphoid depletion in splenic white pulp with increased levels of serum
      transaminases, lactate dehydrogenase, and hepatic malondialdehyde, tumor necrosis
      factor-alpha and interleukin 6; and number of caspase 3- and Bax-positive
      hepatocytes. A significant decrease in leukocyte counts, serum immunoglobulins
      (IgA, IgM and IgG) level, and hepatic antioxidant enzymes (GSH, GPx, SOD, and
      CAT) was also detected. Pretreatment with SP resulted in significant improvements
      in hepatic and splenic histologic architecture, as well as restoring liver
      enzymes and reduction of lipid peroxidation product, proinflammatory cytokines,
      and caspase 3 and Bax immunoexpression. Additionally, a significant increase in
      antioxidant enzymes, serum immunoglobulins, and total leukocyte counts was
      demonstrated. SIGNIFICANCE: SP possesses promising antioxidant, anti
      inflammatory, anti-apoptotic and immune stimulatory properties against MTX
      induced hepatotoxicity and immunosuppression.

PMID- 29339103
TI  - Comparative review of adult midbrain and striatum neurogenesis with classical
      neurogenesis.
AB  - Parkinson's Disease (PD) motor symptoms are caused by loss of dopamine (DA)
      neurons in the substantia nigra pars compacta (SNc) of the midbrain. Dopamine
      cell replacement therapy (DA CRT), either by cell transplantation or endogenous
      repair, has been a potential treatment to replace dead cells and improve PD motor
      symptoms. Adult midbrain and striatum have been studied for many years to find
      evidence of neurogenesis. Although the literature is controversial, recent
      research has revived the possibility of neurogenesis here. This paper aims to
      review the process of neurogenesis (by focusing on gene expression patterns) in
      the adult midbrain/striatum and compare it with classical neurogenesis that
      occurs in developing midbrain, Sub Ventricular Zone (SVZ) and Sub Granular Zone
      (SGZ) of the adult brain.

PMID- 29339104
TI  - Region-specific innate antiviral responses of the human epididymis.
AB  - Viral infections of the epididymis are associated with epididymitis, which
      damages the epithelium and impairs fertility. We showed previously that innate
      immune response genes were differentially expressed in the corpus and cauda
      region of the human epididymis in comparison to the caput. Here we investigate
      the antiviral defense response mechanisms of human epididymis epithelial (HEE)
      cells. Toll-like receptor (TLR) 3 and retinoic acid-inducible gene I (RIG-I)-like
      receptors (RLRs) are enriched in HEE cells from the corpus and cauda region.
      These HEE cells show an enhanced response to antiviral ligands (poly(I:C) and HSV
      60), as shown by increased IFN-beta mRNA expression and IFN-beta secretion.
      Nuclear translocation of phosphorylated p65 occurs after poly(I:C) exposure. In
      addition, paired box 2 (PAX2), which was implicated in regulating antiviral
      response pathways, is required for basal expression of the DNA sensor, Z-DNA
      binding protein (ZBP1) and type I interferon, in caput but not in cauda cells.

PMID- 29339105
TI  - Effects of thymol on amyloid-beta-induced impairments in hippocampal synaptic
      plasticity in rats fed a high-fat diet.
AB  - Obesity and a high-fat diet (HFD) are known to increase the incidence of
      Alzheimer's disease (AD). Oxidative stress, a major risk factor for AD, is
      increased with HFD consumption. Thymol (Thy) has antioxidant properties.
      Therefore, in the present study, we examined the protective and therapeutic
      effects of Thy on amyloid-beta (Abeta)-induced impairments in the hippocampal
      synaptic plasticity of HFD-fed rats. In this study, 72 adult male Wistar rats
      were randomly assigned to 9 groups (n = 8 rats/group): Group 1 (control; standard
      diet); Group 2: Control + phosphate-buffered saline (PBS) + Oil (Thy vehicle);
      Group 3 (HFD + PBS); Group 4: (HFD + Abeta); Group 5: Control + PBS + Thy; Group
      6: (HFD + Abeta + Oil); Group 7: Control + Abeta + Thy; Group 8: HFD + PBS + Thy;
      Group 9: (HFD + Abeta + Thy). After stereotaxic surgery, the field potentials
      were recorded after the implantation of the recording and stimulating electrodes
      in the dentate gyrus (DG) and perforant pathway, respectively. Following high
      frequency stimulation, the long-term potentiation (LTP) of the population spike
      (PS) amplitude and the slope of the excitatory postsynaptic potentials (EPSPs)
      were measured in the DG. The HFD rats that received Abeta exhibited a significant
      decrease in their EPSP slope and PS amplitude as compared to the control group.
      In contrast, Thy administration in the HFD + Abeta rats reduced the decrease in
      the EPSP slope and PS amplitude. Thy decreased the Abeta-induced LTP impairments
      in HFD rats. The HFD significantly increased serum malondialdehyde levels and
      decreased total antioxidant capacity and total glutathione levels; whereas, Thy
      supplementation significantly reversed these parameters. Therefore, these results
      suggest that Thy, a natural antioxidant, can be therapeutic against high risk
      factors for AD, such as HFD.

PMID- 29339106
TI  - Safinamide: a new hope for Parkinson's disease?
AB  - The loss of dopaminergic neurons (DAn) and reduced dopamine (DA) production
      underlies the reasoning behind the gold standard treatment for Parkinson's
      disease (PD) using levodopa (L-DOPA). Recently licensed by the European Medicine
      Agency (EMA) and US Food and Drug Administration (FDA), safinamide [a monoamine
      oxidase B (MOA-B) inhibitor] is an alternative to L-DOPA; as we discuss here, it
      enhances dopaminergic transmission with decreased secondary effects compared with
      L-DOPA. In addition, nondopaminergic actions (neuroprotective effects) have been
      reported, with safinamide inhibiting glutamate release and sodium/calcium
      channels, reducing the excitotoxic input to dopaminergic neuronal death. Effects
      of safinamide have been correlated with the amelioration of non-motor symptoms
      (NMS), although these remain under discussion. Overall, safinamide can be
      considered to have potential antidyskinetic and neuroprotective effects and
      future trials and/or studies should be performed to provide further evidence for
      its potential as an anti-PD drug.

PMID- 29339107
TI  - Influenza A virus polymerase: an attractive target for next-generation anti
      influenza therapeutics.
AB  - The influenza RNA-dependent RNA polymerase (RdRP) is conserved among different
      types of influenza virus, playing an important part in transcription and
      replication. In this regard, influenza RdRP is an attractive target for novel
      anti-influenza drug discovery. Herein, we will introduce the structural and
      functional information of influenza polymerase; and an overview of inhibitors
      targeting the PA endonuclease and PB2 cap-binding site is provided, along with
      the approaches utilized for identification of these inhibitors. The protein
      protein interactions (PPIs) of the three polymerase subunits: PA, PB1 and PB2,
      are described based on the published crystal structures, and inhibitors targeting
      the PA-PB1 interaction are introduced briefly.

PMID- 29339108
TI  - Phenotype in girls and women with Turner syndrome: Association between dysmorphic
      features, karyotype and cardio-aortic malformations.
AB  - INTRODUCTION: Turner syndrome (TS) is a genetic disorder characterized by the
      (partial) absence or a structural aberration of the second sex chromosome and is
      associated with a variety of phenotypes with specific physical features and
      cardio-aortic malformations. The objective of this study was to gain a better
      insight into the differences in dysmorphic features between girls and women with
      TS and to explore the association between these features, karyotype and cardio
      aortic malformations. METHODS: This prospective study investigated 14 dysmorphic
      features of TS girls and women using a checklist. Three major phenotypic patterns
      were recognized (severe phenotype, lymphatic phenotype and skeletal phenotype).
      Patient data including karyotype and cardio-aortic malformations (bicuspid aortic
      valve (BAV) and aortic coarctation (COA)) were collected. Associations between
      the prevalence of dysmorphic features, karyotype and cardio-aortic malformations
      were analysed using chi2-test and odds ratios. RESULTS: A total of 202 patients
      (84 girls and 118 women) were analysed prospectively. Differences in prevalence
      of dysmorphic features were found between girls and women. A strong association
      was found between monosomy 45,X and the phenotypic patterns. Furthermore, an
      association was found between COA and lymphatic phenotype, but no association was
      found between karyotype and cardio-aortic malformations. CONCLUSION: This study
      uncovered a difference in dysmorphic features between girls and women. Monosomy
      45,X is associated with a more severe phenotype, lymphatic phenotype and skeletal
      phenotype. All patients with TS should be screened for cardio-aortic
      malformations, because in contrast to previous reports, karyotype and cardio
      aortic malformations showed no significant association.

PMID- 29339110
TI  - In vitro anti-diabetic effect of flavonoids and pheophytins from Allophylus
      cominia Sw. on the glucose uptake assays by HepG2, L6, 3T3-L1 and fat
      accumulation in 3T3-L1 adipocytes.
AB  - BACKGROUND AND PURPOSE: Based on ethno-botanical information collected from
      diabetic patients in Cuba and firstly reported inhibition of PTP1B and DPPIV
      enzymes activities, Allophylus cominia (A. cominia) was identified as possible
      source of new drugs that could be used for the treatment of type 2 diabetes
      mellitus (T2-DM). EXPERIMENTAL APPROACH: in this study, the activity of the
      characterised extracts from A. cominia was tested on the glucose uptake using
      HepG2 and L6 cells, 3T3-L1 fibroblasts and adipocytes as well as their effect on
      the fat accumulation using 3T3-L1 adipocytes. KEY RESULTS: on 2-NBDG glucose
      uptake assay using HepG2 and L6 cells, extracts from A. cominia enhanced insulin
      activity by increasing glucose uptake. On HepG2 cells Insulin EC50 of 93 +/- 21nM
      decreased to 13 +/- 2nM in the presence of the flavonoids mixture from A.cominia.
      In L6 cells, insulin also produced a concentration-dependent increase with an
      EC50 of 28.6 +/- 0.7nM; EC50 decreased to 0.08 +/- 0.02nM and 5 +/- 0.9nM in the
      presence of 100MUg/ml of flavonoids and pheophytins mixtures, respectively. In
      3T3-L1 fibroblasts, insulin had an EC50 of >1000nM that decreased to 38 +/- 4nM
      in the presence of the flavonoids extract. However, in adipocytes, insulin
      produced a significant concentration-dependent increase and an EC50 of 30 +/- 8nM
      was a further confirmation of the insulin responsiveness of the adipocytes to the
      insulin. At 100ug/ml, flavonoids and pheophytins extracts decreased fat
      accumulation in 3T3-L1 adipocytes by two folds in comparison to the control
      differentiated cells (p < 0.05). The crude extract of A. cominia did not show any
      enhancement of 2-NBDG uptake by 3T3-L1 adipocytes in the presence or absence of
      100nM insulin. In addition, in fully differentiated adipocytes, both extracts
      produced significant decrease in lipid droplets in the cells and no lipid
      accumulation were seen after withdrawal of the extracts from the cell growth
      medium. However, there was no effect of both extracts on total protein
      concentration in cells as well as on Glut-4 transporters. CONCLUSIONS AND
      IMPLICATIONS: the pharmacological effects of the extracts from A. cominia
      observed in experimental diabetic models were shown in this study. A. cominia is
      potentially a new candidate for the treatment and management of T2-DM.

PMID- 29339109
TI  - Bitter gourd reduces elevated fasting plasma glucose levels in an intervention
      study among prediabetics in Tanzania.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Impaired glucose tolerance and diabetes mellitus
      have become major health issues even in non-industrialized countries. As access
      to clinical management is often poor, dietary interventions and alternative
      medicines are required. For bitter gourd, Momordica charantia L., antidiabetic
      properties have been claimed. AIM OF THE STUDY: The main objective of the
      intervention study was to assess antidiabetic effects of daily bitter gourd
      consumption of 2.5g powder over the course of eight weeks among prediabetic
      individuals. MATERIALS AND METHODS: In a randomized placebo-controlled single
      blinded clinical trial, 52 individuals with prediabetes were studied after
      consuming a bitter gourd or a cucumber juice. For reducing the impact of between
      subject differences in the study population, a crossover design was chosen with
      eight weeks for each study period and four weeks washout in between. Fasting
      plasma glucose was chosen as the primary outcome variable. RESULTS: Comparing the
      different exposures, the CROS analysis (t=-2.23, p=0.031, r=0.326) revealed a
      significant difference in the change of FPG of 0.31mmol/L (5.6mg/dL) with a trend
      (R2=0,42387). The number of 44 finally complete data sets achieved a power of
      0.82, with a medium-to-large effect size (Cohen's d 0.62). The effect was also
      proven by a general linear mixed model (estimate 0.31; SE: 0.12; p: 0.01; 95%CI:
      0.08; 0.54). Not all participants responded, but the higher the initial blood
      glucose levels were, the more pronounced the effect was. No serious adverse
      effects were observed. CONCLUSIONS: Bitter gourd supplementation appeared to have
      benefits in lowering elevated fasting plasma glucose in prediabetes. The findings
      should be replicated in other intervention studies to further investigate glucose
      lowering effects and the opportunity to use bitter gourd for dietary self
      management, especially in places where access to professional medical care is not
      easily assured.

PMID- 29339111
TI  - Stem Cells for Urinary Incontinence: Functional Differentiation or Cytokine
      Effects?
AB  - Minimally invasive stem cell therapy for stress urinary incontinence may provide
      an effective nonsurgical treatment for this common condition. Clinical trials of
      periurethral stem cell injection have been under way, and basic science research
      has demonstrated the efficacy of both local and systemic stem cell therapies.
      Results differ as to whether stem cells have a therapeutic effect by
      differentiating into permanent, functional tissues or exert benefits through a
      transient presence and the secretion of regenerative factors. This review
      explores the fate of therapeutic stem cells for stress urinary incontinence and
      how this may relate to their mechanism of action.

PMID- 29339112
TI  - Reply to: "Reply to: 'Response to DAA therapy in the NHS England Early Access
      Programme for rare HCV subtypes from low and middle income countries'".

PMID- 29339113
TI  - Development of the liver: Insights into organ and tissue morphogenesis.
AB  - Recent development of improved tools and methods to analyse tissues at the three
      dimensional level has expanded our capacity to investigate morphogenesis of
      foetal liver. Here, we review the key morphogenetic steps during liver
      development, from the prehepatic endoderm stage to the postnatal period, and
      consider several model organisms while focussing on the mammalian liver. We first
      discuss how the liver buds out of the endoderm and gives rise to an asymmetric
      liver. We next outline the mechanisms driving liver and lobe growth, and review
      morphogenesis of the intra- and extrahepatic bile ducts; morphogenetic responses
      of the biliary tract to liver injury are discussed. Finally, we describe the
      mechanisms driving formation of the vasculature, namely venous and arterial
      vessels, as well as sinusoids.

PMID- 29339114
TI  - A systematic review and meta-analysis of cardiorespiratory fitness among
      Indigenous populations in North America and circumpolar Inuit populations.
AB  - Indigenous populations experience health disparities including increased obesity,
      diabetes and cardiovascular disease rates. Cardiorespiratory fitness is
      beneficial for maintaining positive health outcomes. The objective of this
      systematic review is to evaluate cardiorespiratory fitness among Indigenous
      populations including comparisons across genders, Indigenous identities, age
      groups, decades, socio-demographic variables and in comparison to non-Indigenous
      groups. Included articles reported various cardiorespiratory fitness measures
      using maximal treadmill or cycle ergometer tests, 20 m shuttle run, 1 mile
      run/walk test and 6 min walk test. From 14 databases searched in March 2017,
      including MEDLINE, EMBASE and Scopus, 1069 citations were evaluated and 39
      articles included, representing 32 investigations and 10,579 individuals. First
      Nations/American Indian (FN/AI) adults have greater cardiorespiratory fitness
      than Inuit. Inuit and FN/AI men and boys have higher cardiorespiratory fitness
      than women and girls. Lower cardiorespiratory fitness is associated with obesity,
      metabolic syndrome and a western lifestyle. Cardiorespiratory fitness has
      declined among Inuit adults, averaging 51.7 +/- 7.9 mL.kg-1.min-1 in 1970 to 37.7
      +/- 6.9 mL.kg-1.min-1 in 2000. Among men, FN/AI have greater cardiorespiratory
      fitness compared to European-descents, and European-descents have greater
      cardiorespiratory fitness compared to Inuit. The 1 mile run/walk time showed that
      FN/AI boys, girls, and youth had faster times compared to European-descendants,
      but 20 m shuttle run showed that European-descent boys and youth advanced to
      further stages compared to FN/AI populations. Cardiorespiratory fitness is
      declining, and among some Indigenous populations to lower levels than European
      descent populations. Improving cardiorespiratory fitness for Indigenous
      populations should be considered a primary health strategy.

PMID- 29339115
TI  - Toddler drinks, formulas, and milks: Labeling practices and policy implications.
AB  - Toddler drinks are a growing category of drinks marketed for young children 9-36
      months old. Medical experts do not recommend them, and public health experts
      raise concerns about misleading labeling practices. In the U.S., the toddler
      drink category includes two types of products: transition formulas, marketed for
      infants and toddlers 9-24 months; and toddler milks, for children 12-36 months
      old. The objective of this study was to evaluate toddler drink labeling practices
      in light of U.S. food labeling policy and international labeling recommendations.
      In January 2017, we conducted legal research on U.S. food label laws and
      regulations; collected and evaluated toddler drink packages, including nutrition
      labels and claims; and compared toddler drink labels with the same brand's infant
      formula labels. We found that the U.S. has a regulatory structure for food labels
      and distinct policies for infant formula, but no laws specific to toddler drinks.
      Toddler drink labels utilized various terms and images to identify products and
      intended users; made multiple health and nutrition claims; and some stated there
      was scientific or expert support for the product. Compared to the same
      manufacturer's infant formula labels, most toddler drink labels utilized similar
      colors, branding, logos, and graphics. Toddler drink labels may confuse consumers
      about their nutrition and health benefits and the appropriateness of these
      products for young children. To support healthy toddler diets and well-informed
      decision-making by caregivers, the FDA can provide guidance or propose
      regulations clarifying permissible toddler drink labels and manufacturers should
      end inappropriate labeling practices.

PMID- 29339116
TI  - Understanding Women's Subjective Sexual Arousal Within the Laboratory:
      Definition, Measurement, and Manipulation.
AB  - INTRODUCTION: Subjective sexual arousal (SSA) is positive, cognitive engagement
      in sexual activity. SSA is considered an important aspect of the sexual
      experience, as it has been found to facilitate sexual activity and, in situations
      of chronically low or absent arousal, potentially cause distress. Despite the
      clinical implications of SSA, a thorough review of how to manipulate SSA has yet
      to be conducted. AIM: To review the state of knowledge about SSA in women,
      including its definition, measurement, and the outcomes of studies attempting to
      manipulate SSA within a laboratory setting. METHOD: A comprehensive search of the
      electronic databases of PubMed and PsycINFO was conducted. The generated list of
      articles was reviewed and duplicates were removed. Individual articles were
      assessed for inclusion and, when appropriate, relevant content was extracted.
      MAIN OUTCOME MEASURE: The potential effects of various manipulations of SSA in a
      laboratory setting was the main outcome. RESULTS: 44 studies were included in
      this review. Manipulations were grouped into 3 primary categories:
      pharmacological (n = 16), cognitive (n = 22), and those based on changes to the
      autonomic nervous system (n = 6). Results suggest that cognitive manipulation is
      the most effective method of increasing SSA. Altering the relative balance of the
      2 branches of the autonomic nervous system (the sympathetic nervous system and
      the parasympathetic nervous system) also appears to be a promising avenue for
      increasing SSA. CONCLUSION: This review supports the use of cognitive
      manipulation for increasing women's SSA in a laboratory setting. Avenues for
      future research and recommendations for clinicians are discussed. Handy AB,
      Stanton AM, Meston CM. Understanding Women's Subjective Sexual Arousal Within the
      Laboratory: Definition, Measurement, and Manipulation. Sex Med Rev 2018;6:201
      216.

PMID- 29339117
TI  - Expression, activation and processing of a novel plant milk-clotting aspartic
      protease in Pichia pastoris.
AB  - Galium verum, also known as Lady's Bedstraw or Cheese Rennet, is an herbaceous
      perennial plant traditionally used in cheese-making. We used RACE PCR to isolate
      novel enzymes from Galium verum with the ability to clot milk. This approach
      generated two cDNA sequences (named preprogaline A and B) encoding proteins
      displaying the typical plant aspartic protease primary structure. Preprogaline B
      was expressed in the yeast Pichia pastoris, after deleting and replacing its
      original signal peptide with the yeast alpha-factor signal peptide from
      Saccharomyces cerevisiae. The secreted recombinant protein was obtained by
      growing P. pastoris in YPD medium and had the ability to clot milk. The mature
      form of progaline B is a heterodimeric glycosylated enzyme, with a molecular
      weight of approximately 48 kDa, that contains a heavy (30.7 kDa) and a light
      (13.5 kDa) polypeptide chains linked by disulfide bonds. Western blot analysis
      revealed that progaline B is activated by the acidification of the yeast culture
      medium and that enzymatic activation requires two steps. First the precursor
      protein is cleaved into two polypeptide chains by partial removal of the plant
      specific insert (PSI) present in plant aspartic proteases; this is later followed
      by propeptide removal. By altering the pH of the P. pastoris culture medium, we
      were able to obtain either active or inactive forms of the enzyme. Recombinant
      progaline B displayed a kappa-casein hydrolysis pattern analogous to those
      produced by the animal and microbial coagulants currently used in the dairy
      industry, but it exhibited a different digestion profile on alpha- and beta
      caseins. The plant protease progaline B displays milk-clotting activities
      suitable for the production of novel dairy products.

PMID- 29339118
TI  - Aerobic and anaerobic cellulose utilization by Paenibacillus sp. CAA11 and
      enhancement of its cellulolytic ability by expressing a heterologous
      endoglucanase.
AB  - For cost-effective lignocellulosic biofuel/chemical production, consolidated
      bioprocessing (CBP)-enabling microorganisms utilizing cellulose as well as
      producing biofuel/chemical are required. A novel strain Paenibacillus sp. CAA11
      isolated from sediment was found to be not only as a cellulose degrader under
      both aerobic and strict anaerobic conditions but also as a producer of cellulosic
      biofuel/chemicals. Paenibacillus sp. CAA11 secreted cellulolytic enzymes by its
      own secretion system and produced ethanol as well as short-chain organic acids
      (formic acid, acetic acid, lactic acid) from cellulose. Cellulolytic activity of
      the strain was significantly enhanced by expressing a heterologous endoglucanase
      168Cel5 from Bacillus subtilis under both aerobic and anaerobic conditions. The
      strain harboring the 168cel5 gene revealed 2-fold bigger halo zone on Congo-red
      plate and 1.75-fold more aerobic cellulose utilization in liquid medium compared
      with the negative control. Notably, under anaerobic conditions, the recombinant
      strain expressing 168Cel5 consumed 1.83-fold more cellulose (5.10 g/L) and
      produced 5-fold more ethanol (0.65 g/L) along with 5-fold more total acids (1.6
      g/L) compared with the control, resulting 2.73-fold higher yields. This result
      demonstrates the potential of Paenibacillus sp. CAA11 as a suitable aerobic and
      anaerobic CBP-enabling microbe with cellulolytic production of ethanol and short
      chain organic acids.

PMID- 29339119
TI  - Targeting of stress response pathways in the prevention and treatment of cancer.
AB  - The hallmarks of tumor tissue are not only genetic aberrations but also the
      presence of metabolic and oxidative stress as a result of hypoxia and lactic
      acidosis. The stress activates several prosurvival pathways including metabolic
      remodeling, autophagy, antioxidant response, mitohormesis, and glutaminolysis,
      whose upregulation in tumors is associated with a poor survival of patients,
      while their activation in healthy tissue with statins, metformin, physical
      activity, and natural compounds prevents carcinogenesis. This review emphasizes
      the dual role of stress response pathways in cancer and suggests the integrative
      understanding as a basis for the development of rational therapy targeting the
      stress response.

PMID- 29339120
TI  - Symmetry of peripheral retinal nonperfusion in diabetic retinopathy by ischemic
      index.
AB  - PURPOSE: Diabetic retinopathy is the leading cause of blindness among working-age
      adults in most developed countries. It affects eyes bilaterally and is generally
      believed to be symmetrical, yet there are few studies evaluating the symmetry of
      diabetic retinopathy. The purpose of the present study was to evaluate the
      symmetry of the amount of peripheral retinal ischemia in patients with diabetic
      retinopathy. METHODS: Ultra-widefield fluorescein angiography images were
      obtained on both eyes of 54 subjects, mean age 56.4 years, from an urban eye
      clinic. A single, high quality image from the arteriovenous phase of the
      angiogram of each eye was selected for analysis. The total area of gradable
      fundus and area of nonperfusion seen in the arteriovenous phase of the ultra
      widefield fluorescein angiogram were determined. An ischemic index (ISI) was
      calculated by dividing the non-perfused retinal area by the total retinal area
      and multiplying by 100. RESULTS: The mean ISI OD was 11.27, mean ISI OS was
      11.64. The mean absolute value (+/-SD) of ISI difference between OD and OS was
      4.46+/-6.09. A difference in ISI of 10% or less was found in 92.6% of subjects. A
      statistically significant correlation was found in the ISI between right and left
      eyes (rs=0.80, p<0.0001) and there was no statistically significant difference in
      ISI between the right and left eyes (p=0.85). CONCLUSION: Asymmetrical
      retinopathy in diabetic patients is uncommon and additional pathological
      processes should be considered in the presence of asymmetric DR.

PMID- 29339122
TI  - Regnase-1, an Immunomodulator, Limits the IL-36/IL-36R Autostimulatory Loop in
      Keratinocytes to Suppress Skin Inflammation.

PMID- 29339121
TI  - HSF1, in association with MORC2, downregulates ArgBP2 via the PRC2 family in
      gastric cancer cells.
AB  - Arg Kinase-binding protein 2 (ArgBP2) is considered to be a scaffold protein that
      coordinates multiple signaling pathways converging on cell adhesion and actin
      cytoskeletal organization. It also plays an important role in blocking cancer
      metastasis as a potential tumor suppressor. However, its regulation mechanisms in
      tumor migration, especially in gastric cancer, are not fully understood. Here, we
      identified an ArgBP2 enhancer and showed that heat shock factor 1 (HSF1) directly
      interacted with microrchidia CW-type zinc finger 2 (MORC2) and bound to the
      enhancer of ArgBP2. HSF1 was found to promote proliferation, migration and
      invasion of gastric cancer cells. HSF1 or/and MORC2 increased recruitment of the
      polycomb repressive complex 2 (PRC2), particularly enhancer of zeste homolog 2
      (EZH2), to the ArgBP2 enhancer and catalyzed tri-methylation of lysine 27 on
      histone H3 (H3K27me3), leading to transcriptional repression of ArgBP2. In
      addition, HSF1 and MORC2-induced migration and invasion in gastric cancer cells
      was dependent on ArgBP2 or EZH2. Clinical data exhibited a negative correlation
      of ArgBP2 with MORC2, HSF1, and EZH2. Our results thus contribute to the
      knowledge of the regulatory mechanism of HSF1 in down-regulating ArgBP2,
      providing new insight into the HSF1&MORC2-PRC2-ArgBP2 signaling pathway and a
      better understanding of their functions in gastric cancer cells.

PMID- 29339123
TI  - Identical twins with XLA requiring differing amounts of 20% subcutaneous
      immunoglobulin secondary to protein-losing enteropathy.

PMID- 29339124
TI  - The first case of methemoglobinemia associated with omalizumab.

PMID- 29339125
TI  - Prevalence and Outcomes of Primary Immunodeficiency in Hospitalized Children in
      the United States.
AB  - BACKGROUND: Primary immunodeficiency diseases (PIDDs) are rare yet life
      threatening chronic conditions in children. The prevalence and outcomes of PIDDs
      in the pediatric population in the United States are not well understood.
      OBJECTIVE: The objectives of this study were to (1) determine the epidemiology of
      children hospitalized with PIDD in the United States and (2) characterize the
      clinical outcomes of hospitalized children with PIDDs. METHODS: Retrospective
      cohort analysis of the 2003-2012 Kids' Inpatient Database of children aged 2-18
      years admitted with a primary or secondary diagnosis code of PIDD was performed.
      Secondary immunodeficiency diseases were excluded. RESULTS: There were 26,794
      pediatric patients hospitalized with a diagnosis of a PIDD from 2003 to 2012. The
      national prevalence of all PIDDs per 100,000 was 66.6, 82.2, 97.4, and 126.8 in
      2003, 2006, 2009, and 2012, respectively. The highest prevalence was in children
      0-5 years of age (15,105 hospitalizations; 56%). There was no difference in
      prevalence between B-cell defects and T-cell defects. PIDDs affected all ethnic
      populations equally. Respiratory-related diagnoses were the most common
      comorbidity by an organ system. Overall mortality was 1.99%. Age was inversely
      correlated with clinical outcome. Children 0-5 years had higher mortality (424
      deaths, 79.85%), mean hospital charges ($35,480), and length of stay (LOS) (5.6
      days) compared with older age cohorts. CONCLUSIONS: The prevalence of PIDDs in
      the hospitalized pediatric population in the United States may have increased
      over time. Younger age is associated with higher mortality, hospital costs, and
      LOS. Further study is needed to determine cost-effective management strategies to
      improve outcomes in infants and young children with PIDD.

PMID- 29339126
TI  - Addressing the Impact and Unmet Needs of Nonadherence in Asthma and Chronic
      Obstructive Pulmonary Disease: Where Do We Go From Here?
AB  - Nonadherence to treatment, and its associated health and economic burden, is
      particularly problematic in asthma and chronic obstructive pulmonary disease
      management because of heterogeneous patient populations and the need for an
      inhaled route of drug administration. Symptom variability, comorbidities, and
      device switching further add to suboptimal adherence rates. As opposed to
      controlled clinical trials, real-life studies show consistently low inhaler
      adherence in daily practice, yet exact adherence rates have long been affected by
      disagreement on standardized definitions. The recently developed Ascertaining
      Barriers to Compliance taxonomy helps to address adherence research disparities
      by identifying 3 phases of adherence (initiation, implementation [including
      correct inhaler technique], and discontinuation). This review considers the
      reasons for and impact of suboptimal adherence, together with summaries of key
      studies that demonstrate how improving adherence can reduce exacerbations,
      inhaled corticosteroid use (in cases of better inhaler technique),
      hospitalizations, and treatment costs. Strategies to help ensure optimal
      adherence are discussed, including the choice of a patient-tailored inhaler,
      patient empowerment, education and training, and the potential of electronic
      monitoring and digital technology. It is concluded that a combined effort from
      payers, health care professionals, and manufacturers could make a real difference
      to asthma and chronic obstructive pulmonary disease control, as well as to health
      care budgets.

PMID- 29339127
TI  - The Basophil Activation Test Can Be of Value for Diagnosing Immediate Allergic
      Reactions to Omeprazole.
AB  - BACKGROUND: Proton pump inhibitors (PPIs) are commonly used to treat
      gastrointestinal diseases. Incidence of hypersensitivity reactions to PPIs has
      risen, likely because of increased consumption. Their diagnosis is difficult,
      with skin tests (STs) presenting low sensitivity, making it necessary to perform
      drug provocation tests (DPTs). The value of in vitro tests for the diagnosis of
      immediate reaction to PPI is unclear. OBJECTIVE: To analyze the diagnostic value
      of the basophil activation test (BAT) in a group of patients diagnosed with
      immediate allergy to omeprazole. METHODS: The study included 42 patients with
      confirmed immediate allergic reactions to omeprazole confirmed by positive ST
      results or DPT results and 22 age- and sex-matched subjects tolerant to PPIs. BAT
      was performed with omeprazole, pantoprazole, and lansoprazole using CD63 and
      CD203c as activation markers. RESULTS: ST sensitivity was 66.7% with a
      specificity of 100%. BAT using CD63 with a stimulation index of more than 2 as
      positive revealed a sensitivity of 73.8%, a specificity of 100%, a positive
      predictive value of 100%, and a negative predictive value of 66.7%. BAT was
      positive in 57.1% of patients with negative ST result, and thus by combining ST
      and BAT we can correctly diagnose 85.7% of patients with immediate allergy to
      omeprazole. CONCLUSION: BAT represents a complementary tool for inclusion in the
      allergological workup for patients allergic to omeprazole. When combined with ST,
      it can be of value to guide the clinician as to whether to perform a DPT.

PMID- 29339128
TI  - Anxiety and Depression Effects During Drug Provocation Test.
AB  - BACKGROUND: Drug provocation test (DPT) represents the gold standard for the
      diagnosis of drug allergy. A DPT can be performed in a single-blind placebo
      controlled manner. In anxiety and depressive disorders, patients need to be
      evaluated to understand the nature of placebo reactions. OBJECTIVE: The aim of
      this study was to evaluate the psychological profile of patients with reactions
      to placebo during a DPT. METHODS: We consecutively enrolled patients with
      suspected drug allergy undergoing a DPT preceded by the administration of the
      placebo. All patients underwent the Hospital Anxiety and Depression Scale (HADS),
      a questionnaire aimed to identify anxiety and depression, before the challenge
      test. RESULTS: A total of 196 patients were enrolled into this study: 8 (4%)
      patients resulted positive to the DPT, 60 (30.6%) demonstrated anxiety or
      depression based on the HADS, and 54 had at least 1 placebo reaction during drug
      provocation. There were statically significant correlations between the
      positivity of the HADS and the finding of a placebo reaction (Fisher's exact
      test: P < .001), and between the latter and a history of severe reactions to drug
      (Fisher's exact test: P < .001). CONCLUSIONS: There is a significant and strong
      correlation between the loss of psychic equilibrium and the development of a
      placebo reaction during a DPT. We suggest the use the HADS or other validated
      questionnaire in clinical practice before a DPT to evaluate the possible
      psychiatric components.

PMID- 29339129
TI  - Systemic Reactions in Pediatric Patients Receiving Standardized Allergen
      Subcutaneous Immunotherapy with and without Seasonal Dose Adjustment.
AB  - BACKGROUND: The 2003 Joint Task Force on Practice Parameters recommended
      standardizing allergen subcutaneous immunotherapy (SCIT). Data from longitudinal
      surveillance survey in North America reported a systemic reaction (SR) rate of
      0.1% to 0.2% of injection visits. The rate of SR to standardized SCIT in
      pediatric patients has not been well evaluated. OBJECTIVE: The objective of this
      study was to evaluate the rate of SRs to standardized SCIT in pediatric patients
      aged 5 to 18 years in a single tertiary care center in the United States.
      METHODS: A retrospective chart review was conducted in 2 groups: group 1 started
      SCIT within a period extending from January 2009 to June 2012, whereas group 2
      started SCIT within a period extending from January 2013 to June 2016. The
      protocol was modified in group 2 such that updosing and maintenance doses were
      adjusted in the spring for tree and grass pollen and in the fall for weed pollen.
      RESULTS: There were a total of 128 patients in group 1 and 118 patients in group
      2. The rate of SR was 0.429% in group 1 and 0.364% in group 2, which was not
      significant. There was no difference in the severity of SR in the 2 groups with
      no-fatal or near-fatal SR noted. Asthma was a significant risk factor in the
      younger age subgroup aged 5 to 11 years. CONCLUSIONS: Standardized SCIT appears
      to be associated with an SR rate of 0.429% to 0.364% of visits in pediatric
      patients. Protocol modification did not lead to a significant drop in SR. Larger
      multicenter studies are required to further evaluate the rate of SRs from
      standardized SCIT.

PMID- 29339130
TI  - Fixed Drug Eruption Related to Cefixime in an Adolescent Case.

PMID- 29339132
TI  - Exogenous progesterone hypersensitivity associated with recurrent pregnancy loss.

PMID- 29339131
TI  - Childhood Asthma: Is It All About Bacteria and Not About Viruses? A Pro/Con
      Debate.

PMID- 29339133
TI  - Antithrombin III-Binding Site Analysis of Low-Molecular-Weight Heparin Fractions.
AB  - Low-molecular-weight heparins (LMWHs) are widely used as clinical anticoagulant
      drugs. LMWHs are heterogeneous and highly negatively charged glycans prepared by
      chemical or enzymatic depolymerization of unfractionated heparin. The detailed
      structural analysis of a LMWH is essential for the drug quality control. In this
      study, an LMWH, enoxaparin sodium (a generic version of Lovenox) was separated
      into different molecular weight fractions by a Superdex peptide column. The
      disaccharide compositions, 3-O-sulfo group-containing tetrasaccharides
      composition, and antithrombin III-binding affinity of the fractions from this
      LMWH were analyzed. The results showed that all the fractions had very similar
      disaccharide and 3-O-sulfo group-containing tetrasaccharide compositions, but the
      fraction containing larger-sized chains had higher antithrombin III-binding
      affinity.

PMID- 29339134
TI  - A Small-Scale Process for Predicting Donnan and Volume Exclusion Effects During
      Ultrafiltration/Diafiltration Process Development.
AB  - Achieving the desired final protein formulation using
      ultrafiltration/diafiltration (UF/DF) operations is an essential component of
      many protein purification processes. It is well documented that differences in
      the excipient and buffer concentrations exist between the DF and retentate
      solutions when they have achieved equilibrium. Several publications have proposed
      ways to calculate these differences. However, the accuracy of these methods has
      been limited by the use of an estimated protein charge value. In this article, a
      small-scale system is described, which can accurately determine the protein
      charge by making buffer and excipient concentration measurements and applying the
      determined values to the Donnan and volume exclusion equations. This information
      can be utilized to generate a standard curve, which in turn can be applied to at
      scale UF/DF operations. For 2 different antibodies, the standard curve generated
      by the small-scale system yielded buffer concentrations and pH values that agreed
      well with those generated after UF/DF operations, whereas using the theoretical
      protein charge caused a departure from the measured results. This model also
      provides good estimates as to how the final formulation pH and buffer
      concentration vary as a function of the pH and buffer concentration in the DF
      buffer. This information is of important utility for the accurate formulation of
      high-concentration protein solutions (>100 mg/mL) where the coconcentration of
      buffers and the volume exclusion of certain excipients are amplified. The low
      material requirements of the small-scale system are a major benefit for early
      phase formulation and process development when sufficient time and material may
      not be available, in particular to ensure successful UF/DF operations for the
      development of high protein concentration formulations.

PMID- 29339135
TI  - Quantitative Monitoring the Anti-Solvent Crystallization and Storage Process for
      Nandrolone by Near-Infrared Spectroscopy.
AB  - A novel hydrate (SH2O) of nandrolone was prepared by anti-solvent methods. The
      crystallization processes with 2 schemes (A and B) were monitored by in-line near
      infrared (NIR) spectroscopy. The amounts of SH2O in powder samples obtained by
      the anti-solvent crystallization and storage process were quantified by NIR
      combined with chemometrics methods. In-line NIR spectra from 4500 to 8000 cm-1
      were chosen to capture physicochemical changes during the whole crystallization
      process. The combination of the principal component results with offline
      characterization (scanning electron microscopy, powder X-ray diffraction, NIR)
      data showed that both schemes yielded high purity SH2O products, but the
      crystallization speed of scheme B was significantly accelerated. It was
      demonstrated that in-line NIR spectroscopy combined with principal component
      analysis can be very useful to monitor in real time and control the anti-solvent
      crystallization process. Moreover, the solubility and the solid-state
      transformation of nandrolone under different storage conditions were
      investigated. The apparent solubility of SH2O was 2.19-2.44 times of Form I, and
      SH2O was relatively stable when stored at a high relative humidity and
      temperature below 25 degrees C.

PMID- 29339136
TI  - Development of Orally Applicable, Combinatorial Drug-Loaded Nanoparticles for the
      Treatment of Fibrosarcoma.
AB  - Nanoparticulate systems have been receiving a significant attention especially
      for the treatment of cancer but one of the main hurdles is to produce these
      developed and high-tech nanosystems in large quantities. Anticancer drug
      formulations are generally designed for parenteral administrations but oral
      administration is still the most convenient route. In this study, orally
      applicable nano-sized chitosan nanoparticles (NPs) were successfully prepared
      using Nano Spray Dryer. It is possible to produce these NPs in large quantities
      by simply increasing the processing time using the machine without changing any
      parameter. A chemotherapeutic agent (imatinib mesylate; IMA) and nonsteroidal
      anti-inflammatory drug (dexketoprofen trometamol) were loaded together in these
      NPs. NPs were also functionalized with polyethylene glycol and folic acid to
      obtain long circulating NPs and tumor targeting. The antitumoral activities of
      formulations showed that these developed NPs can enhance the effectiveness.
      Animal experiments were performed on fibrosarcoma-bearing mice model, and the
      treatment with 0.8 mg/MUL/kg IMA-loaded chitosan NPs was found to be successful
      to slow down the growth of tumors. The tumor tissues were removed from the
      animals and enzymatic activities were evaluated. The inhibitory effect of
      tyrosine kinase was found to be enhanced from 36.4% to 68.4% when IMA was used in
      combination with dexketoprofen trometamol. Furthermore, all dried NPs were found
      to be stable for more than a year at 25 degrees C. Presented results show that
      these developed combinatorial drug-loaded NPs can be used for the treatment of
      fibrosarcoma, and these data can provide an insight, new strategies for
      productions or alternatives in cancer treatment.

PMID- 29339137
TI  - Oxygen-induced alterations in the expression of chromatin modifying enzymes and
      the transcriptional regulation of imprinted genes.
AB  - Embryo culture and assisted reproductive technologies have been associated with a
      disproportionately high number of epigenetic abnormalities in the resulting
      offspring. However, the mechanisms by which these techniques influence the
      epigenome remain poorly defined. In this study, we evaluated the capacity of
      oxygen concentration to influence the transcriptional control of a selection of
      key enzymes regulating chromatin structure. In mouse embryonic stem cells, oxygen
      concentrations modulated the transcriptional regulation of the TET family of
      enzymes, as well as the de novo methyltransferase Dnmt3a. These transcriptional
      changes were associated with alterations in the control of multiple imprinted
      genes, including H19, Igf2, Igf2r, and Peg3. Similarly, exposure of in vitro
      produced bovine embryos to atmospheric oxygen concentrations was associated with
      disruptions in the transcriptional regulation of TET1, TET3, and DNMT3a, along
      with the DNA methyltransferase co-factor HELLS. In addition, exposure to high
      oxygen was associated with alterations in the abundance of transcripts encoding
      members of the Polycomb repressor complex (EED and EZH2), the histone
      methyltransferase SETDB1 and multiple histone demethylases (KDM1A, KDM4B, and
      KDM4C). These disruptions were accompanied by a reduction in embryo viability and
      suppression of the pluripotency genes NANOG and SOX2. These experiments
      demonstrate that oxygen has the capacity to modulate the transcriptional control
      of chromatin modifying genes involved in the establishment and maintenance of
      both pluripotency and genomic imprinting.

PMID- 29339139
TI  - Improved coronary magnetic resonance angiography using gadobenate dimeglumine in
      pediatric congenital heart disease.
AB  - BACKGROUND: CMRA in pediatrics remains challenging due to the smaller vessel
      size, high heart rates (HR), potential image degradation caused by limited
      patient cooperation and long acquisition times. High-relaxivity contrast agents
      have been shown to improve coronary imaging in adults, but limited data is
      available in children. We sought to investigate whether gadobenate dimeglumine
      (Gd-BOPTA) together with self-navigated inversion-prepared coronary magnetic
      resonance angiography (CMRA) sequence design improves coronary image quality in
      pediatric patients. METHODS: Forty consecutive patients (mean age 6+/-2.8years;
      73% males) were prospectively recruited for a 1.5-T MRI study under general
      anesthesia. Two electrocardiographic-triggered free breathing steady-state free
      precession (SSFP) angiography sequences (A and B) with isotropic spatial
      resolution (1.3mm3) were acquired using a recently developed image-based self
      navigation technique. Sequence A was acquired prior to contrast administration
      using T2 magnetization preparation (T2prep). Sequence B was acquired 5-8min after
      a bolus of Gd-BOPTA with the T2prep replaced by an inversion recovery (IR) pulse
      to null the signal from the myocardium. Scan time, signal-to noise and contrast
      to-noise ratios (SNR and CNR), vessel wall sharpness (VWS) and qualitative visual
      score for each sequence were compared. RESULTS: Scan time was similar for both
      sequences (5.3+/-1.8 vs 5.2+/-1.5min, p=.532) and average heart rate (78+/-14.7
      vs 78+/-14.5bpm, p=.443) remained constant throughout both acquisitions. Sequence
      B resulted in higher SNR (12.6+/-4.4 vs 31.1+/-7.4, p<.001) and CNR (9.0+/-1.8 vs
      13.5+/-3.7, p<.001) and provided improved coronary visualization in all coronary
      territories (VWS A=0.53+/-0.07 vs B=0.56+/-0.07, p=.001; and visual scoring
      A=3.8+/-0.59 vs B=4.1+/-0.53, p<.001). The number of non-diagnostic coronary
      segments was lower for sequence B [A=42 (13.1%) segments vs B=33 (10.3%)
      segments; p=.002], and contrary to the pre-contrast sequence, never involved a
      proximal segment. These results were independent of the patients' age, body
      surface area and HR. CONCLUSIONS: The use of Gd-BOPTA with a 3D IR SSFP CMRA
      sequence results in improved coronary visualization in small infants and young
      children with high HR within a clinically acceptable scan time.

PMID- 29339138
TI  - Hyperglycaemia disrupts conducted vasodilation in the resistance vasculature of
      db/db mice.
AB  - Vascular dysfunction in small resistance arteries is observed during chronic
      elevations in blood glucose. Hyperglycaemia-associated effects on endothelium
      dependent vasodilation have been well characterized, but effects on conducted
      vasodilation in the resistance vasculature are not known. Small mesenteric
      arteries were isolated from healthy and diabetic db/db mice, which were used as a
      model of chronic hyperglycaemia. Endothelium-dependent vasodilation via the Gq/11
      coupled proteinase activated receptor 2 (PAR2) was stimulated with the selective
      agonist SLIGRL. The Ca2+-sensitive fluorescent indicator fluo-8 reported changes
      in endothelial cell (EC) [Ca2+]i, and triple cannulated bifurcating mesenteric
      arteries were used to study conducted vasodilation. Chronic hyperglycaemia did
      not affect either EC Ca2+ or local vasodilation to SLIGRL. However, both acute
      and chronic exposure to high glucose or the mannitol osmotic control attenuated
      conducted vasodilation to 10MUM SLIGRL. This investigation demonstrates for the
      first time that a hypertonic solution containing glucose or mannitol can
      interfere with the spread of a hyperpolarizing current along the endothelium in a
      physiological setting. Our findings reiterate the importance of studying the
      effects of hyperglycaemia in the vasculature, and provide the basis for further
      studies regarding the modulation of junctional proteins involved in cell to cell
      communication by diseases such as diabetes.

PMID- 29339140
TI  - [Could we perform vaginal mesh surgery for treatment of pelvic organ prolapse in
      elderly women?]
AB  - INTRODUCTION: Prevalence of pelvic organ prolapse will increase with the aging of
      the population. Concerning the treatment of pelvic organ prolapse, transvaginal
      route is often preferred for elderly women. However few data are available
      concerning transvaginal mesh surgery in this population. The aim of this study
      was to compare efficiency and complications of transvaginal mesh surgery between
      women aged over 75 and younger women. MATERIALS AND METHODS: A monocentric,
      retrospective study included all women who underwent anterior sacrospinous
      suspension with mesh for treatment of pelvic organ prolapse. The primary endpoint
      was anatomical success at the last follow-up, defined by a pelvic organ prolapse
      stage 0 or 1 of POP-Q classification. The secondary endpoints were rate of
      complications and urinary, colorectal and sexual functional results. RESULTS: We
      included 329 patients, 69 were under 75 years old and 260 were aged over 75. The
      median of follow-up was 12 months (IQR: 6). The rate of anatomical success was
      significantly higher in patients aged over 75: 92% versus 85% in younger patients
      (P=0.02). However this difference was no more significant in multivariate
      analysis after inclusion of confusions factors (P=0.82). The rate of
      perioperative complications was low and similar in the 2 groups even in
      multivariate analysis. CONCLUSION: Utero-vaginal suspension using bilateral
      vaginal anterior sacrospinous fixation with mesh seems to achieve at least
      similar results between women aged more than 75 years and younger women. There is
      no excess risk of complications in elderly women. LEVEL OF EVIDENCE: 4.

PMID- 29339141
TI  - [Immunotherapy in renal cell carcinoma: A booming clinical research].
AB  - CONTEXT: Nivolumab, an anti-PD1 immune control point inhibitor, is the first
      treatment that has improved the overall survival of patients after first-line
      metastatic renal cell carcinoma in 2015. Over the past two years, a large number
      of trials on these treatments and the interest of associations are being
      evaluated. OBJECTIVE: In this article, we propose to summarize the clinical
      development of checkpoint inhibitors to assess the direction of clinical research
      in this area. DOCUMENTARY SOURCE: A systematic review of the literature was
      performed in PubMed/Medline database and Meeting Library Asco by searching for
      articles in French or English published on immunotherapy in renal cell carcinoma.
      The research was limited to abstracts and articles published from 2014 to 2017.
      SELECTION OF TRIALS: We identified 349 publications and abstracts and selected 17
      references from prospective studies. RESULTS: Recent data on checkpoint
      inhibitors, as well as their combination with tyrosine kinase inhibitors or with
      anti-angiogenic agents or with indoleamine 2, 3-dioxygenase 1 in renal cell
      carcinoma and the latest advances in vaccine therapy have been reported.
      CONCLUSION: In 2017, immunotherapy combined with other treatments is likely to
      lead to a paradigm shift in the clinical management of patients. The combination
      of nivolumab and ipilimumab in the first line will revolutionize the therapeutic
      management of patients with metastatic renal cell carcinoma.

PMID- 29339142
TI  - [Comment on "Open prostatectomy versus 180-W XPS GreenLight laser vaporization:
      Long-term functional outcome for prostatic adenomas >80g" (Lanchon, in press )].

PMID- 29339143
TI  - Gene silencing reveals multiple functions of Na+/K+-ATPase in the salmon louse
      (Lepeophtheirus salmonis).
AB  - Na+/K+-ATPase has a key function in a variety of physiological processes
      including membrane excitability, osmoregulation, regulation of cell volume, and
      transport of nutrients. While knowledge about Na+/K+-ATPase function in
      osmoregulation in crustaceans is extensive, the role of this enzyme in other
      physiological and developmental processes is scarce. Here, we report
      characterization, transcriptional distribution and likely functions of the newly
      identified L. salmonis Na+/K+-ATPase (LsalNa+/K+-ATPase) alpha subunit in various
      developmental stages. The complete mRNA sequence was identified, with 3003 bp
      open reading frame encoding a putative protein of 1001 amino acids. Putative
      protein sequence of LsalNa+/K+-ATPase revealed all typical features of Na+/K+
      ATPase and demonstrated high sequence identity to other invertebrate and
      vertebrate species. Quantitative RT-PCR analysis revealed higher LsalNa+/K+
      ATPase transcript level in free-living stages in comparison to parasitic stages.
      In situ hybridization analysis of copepodids and adult lice revealed LsalNa+/K+
      ATPase transcript localization in a wide variety of tissues such as nervous
      system, intestine, reproductive system, and subcuticular and glandular tissue.
      RNAi mediated knock-down of LsalNa+/K+-ATPase caused locomotion impairment, and
      affected reproduction and feeding. Morphological analysis of dsRNA treated
      animals revealed muscle degeneration in larval stages, severe changes in the
      oocyte formation and maturation in females and abnormalities in tegmental glands.
      Thus, the study represents an important foundation for further functional
      investigation and identification of physiological pathways in which Na+/K+-ATPase
      is directly or indirectly involved.

PMID- 29339144
TI  - Addressing barriers to effective cancer immunotherapy with nanotechnology:
      achievements, challenges, and roadmap to the next generation of
      nanoimmunotherapeutics.
AB  - Cancer is a complex systemic disorder that affects many organs and tissues and
      arises from the altered function of multiple cellular and molecular mechanisms.
      One of the systems malfunctioning in cancer is the immune system. Restoring and
      improving the ability of the immune system to effectively recognize and eradicate
      cancer is the main focus of immunotherapy, a topic which has garnered recent and
      significant interest. The initial excitement about immunotherapy, however, has
      been challenged by its limited efficacy in certain patient populations and the
      development of adverse effects such as therapeutic resistance and autoimmunity.
      At the same time, a number of advances in the field of nanotechnology have sought
      to address the challenges faced by modern immunotherapeutics and allow these
      therapeutic strategies to realize their full potential. This endeavour requires
      an understanding of not only the immunological barriers in cancer but also the
      mechanisms by which modern technologies and immunotherapeutics modulate the
      function of the immune system. Herein, we summarize the major barriers relevant
      to cancer immunotherapy and review current progress in addressing these obstacles
      using various approaches and clinically approved therapies. We then discuss the
      remaining challenges and how they can be addressed by nanotechnology. We lay out
      translational considerations relevant to the therapies described and propose a
      framework for the development of next-generation nanotechnology-enabled
      immunotherapies.

PMID- 29339146
TI  - Microspheres as intraocular therapeutic tools in chronic diseases of the optic
      nerve and retina.
AB  - Pathologies affecting the optic nerve and the retina are one of the major causes
      of blindness. These diseases include age-related macular degeneration (AMD),
      diabetic retinopathy (DR) and glaucoma, among others. Also, there are genetic
      disorders that affect the retina causing visual impairment. The prevalence of
      neurodegenerative diseases of the posterior segment is increased as most of them
      are related with the elderly. Even with the access to different treatments, there
      are some challenges in managing patients suffering retinal diseases. One of them
      is the need for frequent interventions. Also, an unpredictable response to
      therapy has suggested that different pathways may be playing a role in the
      development of these diseases. The management of these pathologies requires the
      development of controlled drug delivery systems able to slow the progression of
      the disease without the need of frequent invasive interventions, typically
      related with endophthalmitis, retinal detachment, ocular hypertension, cataract,
      inflammation, and floaters, among other. Biodegradable microspheres are able to
      encapsulate low molecular weight substances and large molecules such as
      biotechnological products. Over the last years, a large variety of active
      substances has been encapsulated in microspheres with the intention of providing
      neuroprotection of the optic nerve and the retina. The purpose of the present
      review is to describe the use of microspheres in chronic neurodegenerative
      diseases affecting the retina and the optic nerve. The advantage of
      microencapsulation of low molecular weight drugs as well as therapeutic peptides
      and proteins to be used as neuroprotective strategy is discussed. Also, a new use
      of the microspheres in the development of animal models of neurodegeneration of
      the posterior segment is described.

PMID- 29339147
TI  - Neural signatures for active maintenance and interference during working memory
      updating.
AB  - Although working memory (WM) is amongst the most studied neurocognitive
      functions, temporal patterns of its component processes are not fully understood.
      We examined the neural underpinnings of active maintenance and interference
      management in the n-back task by manipulating load (1-back vs 3-back) and
      including so-called lure stimuli. ERPs of 27 young adults revealed that the 1
      back condition enabling active maintenance showed a positive slow wave (PSW)
      prior to the next stimulus (-600-0 ms) and augmented P2 (190-290 ms) and P3b (330
      430 ms) responses after the stimulus appeared, albeit the latter effects were
      driven by the initial PSW. Moreover, PSW amplitude correlated negatively with
      reaction time in the 1-back condition. Responses to lures showed interference,
      accompanied with different ERP effects for the two load levels. Our results
      support the view that PSW reflects efficient WM maintenance and suggest two
      distinct neuronal correlates for interference in WM.

PMID- 29339148
TI  - Biochemical characterization of Campylobacter jejuni PNPase, an exoribonuclease
      important for bacterial pathogenicity.
AB  - Bacteria need to promptly respond to environmental changes. Ribonucleases
      (RNases) are key factors in the adaptation to new environments by enabling a
      rapid adjustment in RNA levels. The exoribonuclease polynucleotide phosphorylase
      (PNPase) is essential for low-temperature cell survival, affects the synthesis of
      proteins involved in virulence and has an important role in swimming, cell
      adhesion/invasion ability, and chick colonization in C. jejuni. However, the
      mechanism of action of this ribonuclease is not yet known. In this work we have
      characterized the biochemical activity of C. jejuni PNPase. Our results
      demonstrate that Cj-PNP is a processive 3' to 5' exoribonuclease that degrades
      single-stranded RNAs. Its activity is regulated according to the temperature and
      divalent ions. We have also shown that the KH and S1 domains are important for
      trimerization, RNA binding, and, consequently, for the activity of Cj-PNP. These
      findings will be helpful to develop new strategies for fighting against C. jejuni
      and may be extrapolated to other foodborne pathogens.

PMID- 29339149
TI  - SkinEthicTM RHE for in vitro evaluation of skin irritation of medical device
      extracts.
AB  - According to ISO 10993 standards for biocompatibility of medical devices, skin
      irritation is one of the three toxicological endpoints to be always addressed in
      a biological risk assessment. This work presents a new protocol to assess this
      endpoint in vitro rather than in vivo. The protocol was adapted to medical
      devices extracts from the OECD TG 439 with the SkinEthicTM RHE model as test
      system. It was challenged with irritant chemicals, Sodium Dodecyl Sulfate, Lactic
      Acid and Heptanoic Acid spiked in polar solvents, sodium chloride solution or
      phosphate buffer saline and non-polar solvent, Sesame Oil. Cell viability
      measured by MTT reduction after 24 h exposure was used as readout. Quantification
      of IL-1alpha release as secondary readout did not increased performance. Samples
      of heat-pressed polyvinyl chloride (PVC) and silicone sheets infused with or
      without known irritant (4% Genapol-X80, 6% Genapol-X100 and 15% SDS) were tested
      after extraction in polar and non-polar solvents. Medical device extracts are
      classified irritant when the cell viability is inferior or equal to 50%, compared
      to the negative controls tissues, in at least one extraction solvent. The correct
      classification of all the samples confirmed the good performance of this new
      protocol for in vitro skin irritation of medical devices extracts with the
      SkinEthicTM RHE model. Seven naive laboratories were trained in prevision of the
      Round Robin Study to evaluate Reconstructed Human Epidermis (RhE) models as in
      vitro skin irritation test for detection of irritant potential in medical device
      extracts.

PMID- 29339145
TI  - Ocular delivery of proteins and peptides: Challenges and novel formulation
      approaches.
AB  - The impact of proteins and peptides on the treatment of various conditions
      including ocular diseases over the past few decades has been advanced by
      substantial breakthroughs in structural biochemistry, genetic engineering,
      formulation and delivery approaches. Formulation and delivery of proteins and
      peptides, such as monoclonal antibodies, aptamers, recombinant proteins and
      peptides to ocular tissues poses significant challenges owing to their large
      size, poor permeation and susceptibility to degradation. A wide range of advanced
      drug delivery systems including polymeric controlled release systems, cell-based
      delivery and nanowafers are being exploited to overcome the challenges of
      frequent administration to ocular tissues. The next generation systems integrated
      with new delivery technologies are anticipated to generate improved efficacy and
      safety through the expansion of the therapeutic target space. This review will
      highlight recent advances in formulation and delivery strategies of protein and
      peptide based biopharmaceuticals. We will also describe the current state of
      proteins and peptides based ocular therapy and future therapeutic opportunities.

PMID- 29339150
TI  - Altered function of neuronal L-type calcium channels in ageing and
      neuroinflammation: Implications in age-related synaptic dysfunction and cognitive
      decline.
AB  - The rapid developments in science have led to an increase in human life
      expectancy and thus, ageing and age-related disorders/diseases have become one of
      the greatest concerns in the 21st century. Cognitive abilities tend to decline as
      we get older. This age-related cognitive decline is mainly attributed to aberrant
      changes in synaptic plasticity and neuronal connections. Recent studies show that
      alterations in Ca2+ homeostasis underlie the increased vulnerability of neurons
      to age-related processes like cognitive decline and synaptic dysfunctions.
      Dysregulation of Ca2+ can lead to dramatic changes in neuronal functions. We
      discuss in this review, the recent advances on the potential role of dysregulated
      Ca2+ homeostasis through altered function of L-type voltage gated Ca2+ channels
      (LTCC) in ageing, with an emphasis on cognitive decline. This review therefore
      focuses on age-related changes mainly in the hippocampus, and with mention of
      other brain areas, that are important for learning and memory. This review also
      highlights age-related memory deficits via synaptic alterations and
      neuroinflammation. An understanding of these mechanisms will help us formulate
      strategies to reverse or ameliorate age-related disorders like cognitive decline.

PMID- 29339151
TI  - Practical considerations for obtaining high quality quantitative computed
      tomography data of the skeletal system.
AB  - Quantitative CT (QCT) analysis involves the calculation of specific parameters
      such as bone volume and density from CT image data, and can be a powerful tool
      for understanding bone quality and quantity. However, without careful attention
      to detail during all steps of the acquisition and analysis process, data can be
      of poor- to unusable-quality. Good quality QCT for research requires meticulous
      attention to detail and standardization of all aspects of data collection and
      analysis to a degree that is uncommon in a clinical setting. Here, we review the
      literature to summarize practical and technical considerations for obtaining high
      quality QCT data, and provide examples of how each recommendation affects
      calculated variables. We also provide an overview of the QCT analysis technique
      to illustrate additional opportunities to improve data reproducibility and
      reliability. Key recommendations include: standardizing the scanner and data
      acquisition settings, minimizing image artifacts, selecting an appropriate
      reconstruction algorithm, and maximizing repeatability and objectivity during QCT
      analysis. The goal of the recommendations is to reduce potential sources of error
      throughout the analysis, from scan acquisition to the interpretation of results.

PMID- 29339152
TI  - Biogenic triamine and tetraamine activate core catalytic ability of Tetrahymena
      group I ribozyme in the absence of its large activator module.
AB  - Group I intron ribozymes share common core elements that form a three-dimensional
      structure responsible for their catalytic activity. This core structure is
      unstable without assistance from additional factors that stabilize its tertiary
      structure. We examined biogenic triamine and tetraamine and also their fragments
      for their abilities to stabilize a structurally unstable group I ribozyme,
      DeltaP5 ribozyme, derived from the Tetrahymena group I intron ribozyme by
      deleting its large activator module. Biogenic triamine (spermidine) and
      tetraamine (spermine) efficiently activated the DeltaP5 ribozyme under conditions
      where the ribozyme was virtually inactive. These observations suggested that
      polyamines are promising small molecule modulators to activate and possibly
      inhibit the core catalytic ability of group I ribozymes.

PMID- 29339153
TI  - TEMPORARY REMOVAL: Inhibition of COX-2 and 5-LOX regulates the progression of
      colorectal cancer by promoting PTEN and suppressing PI3K/AKT pathway.
AB  - The publisher regrets that this article has been temporarily removed. A
      replacement will appear as soon as possible in which the reason for the removal
      of the article will be specified, or the article will be reinstated. The full
      Elsevier Policy on Article Withdrawal can be found
      athttps://www.elsevier.com/about/our-business/policies/article-withdrawal.

PMID- 29339154
TI  - A new hepatitis B virus e antigen-negative strain gene used as a reference
      sequence in an animal model.
AB  - Infection with hepatitis B virus (HBV) e-antigen (HBeAg)-negative strains is
      increasingly prevalent. Currently, detailed information of the obtained natural
      HBV strain is not available except for the B genotype and HBeAg-negative. The aim
      of the present study was to characterize the natural genetic variation of the
      HBeAg-negative strain and investigate its function. The genic sequence was
      determined using Sanger sequencing, and compared to related sequences using
      alignment and phylogenetic analysis. In vivo, virus-specific serum markers were
      investigated in CBA/CaJ mice. The sequence had a full genome length of 3215
      nucleotides. Sites 122, 125, 127, and 160 in S regions were identified as lysine,
      threonine, proline, and lysine respectively. The main four point variants
      including A1762T, G1764A, G1896A, and G1899A were detected in the full-length
      genome. The genotype of the sequence was B, with sub-genotype B2 and serological
      subtype adw2. The characterize of the natural genetic variation strain showed no
      reported drug-resistant variant in P region and no reported immune escape site in
      S region. The strain will increase viral replication and infection for mutations
      A1762T and G1764A in the basal core promoter region, and mutations G1896A and
      G1899A in the pre-core region. The G1896A variant resulted in a premature stop
      codon and abolished HBeAg expression. HBsAg persisted for 26 weeks and HBeAg was
      still negative in CBA/CaJ mice. The present sequence is representative of the
      HBeAg-negative genome and may serve as a valuable reference for studying HBeAg
      negative strains. The present findings were successfully verified in CBA/CaJ
      mice, demonstrating good applicability of the sequence.

PMID- 29339155
TI  - Truncated CD200 stimulates tumor immunity leading to fewer lung metastases in a
      novel Wistar rat metastasis model.
AB  - CD200 mediates immunosuppression in immune cells that express its receptor,
      CD200R. There are two CD200 variants; truncated CD200 that lacks the part of N
      terminal sequence necessary for CD200R binding (CD200S) and full-length CD200
      (CD200L). We established a novel lung metastasis model by subcutaneously
      transplanting C6 glioma cells into the backs of neonatal Wistar rats. All
      transplanted rats developed large back tumors, nearly 90% of which bore lung
      metastases. To compare the effects of CD200S and CD200L on tumor immunity, CD200L
      (C6-L)- or CD200S (C6-S)-expressing C6 cells were similarly transplanted. The
      results showed that 100% of rats with C6-L tumors developed lung metastases,
      while metastases were found in only 44% of rats with C6-S tumors (n = 25). Tumors
      disappeared in approximately 20% of the C6-S-bearing rats, and these animals
      evaded death 180 d after transplantation, while all C6-L tumor-bearing rats died
      after 45 d. Next generation sequencing revealed that C6-S tumors expressed
      chemokines and granzyme B at much higher levels than C6-L tumors. Flow cytometry
      revealed that C6-S tumors contained more dead cells and more CD45+ cells,
      including natural killer cells and CD8+ lymphocytes. In particular, multiple
      subsets of dendritic cells expressing CD11c, MHC class II, CD8, and/or CD103 were
      more abundant in C6-S than in C6-L tumors. These results suggested that CD200S
      induced the accumulation of multiple dendritic cell subsets that activated
      cytotoxic T lymphocytes, leading to the elimination of metastasizing tumor cells.

PMID- 29339156
TI  - Structure and function of cytoplasmic serine hydroxymethyltransferase from Pichia
      pastoris.
AB  - Serine hydroxymethyltransferase (SHMT) catalyzes the interconversion of serine
      and glycine, which is crucial for one carbon metabolism. Here, we report the
      first crystal structure of cytoplasmic SHMT from Pichia pastoris (pcSHMT)
      diffracted to 2.5 A resolution in space group C2221. PcSHMT was a contaminant
      with our target protein expressed in Pichia pastoris and confirmed by mass
      spectrometry. The overall structure of pcSHMT is similar to Human mitochondrial
      SHMT and different to E. coli SHMT. Interestingly, the oligomerization of pcSHMT
      expressed in eukaryotic or prokaryotic system differs significantly and is
      regulated by pyridoxal-5'-phosphate. Our results revealed a close evolutionary
      relationship between Pichia pastoris and Human mitochondria.

PMID- 29339157
TI  - Drastic stability change of X-X mismatch in d(CXG) trinucleotide repeat disorders
      under molecular crowding condition.
AB  - The trinucleotide repeat d(CXG) (X = A, C, G or T) is the most common sequence
      causing repeat expansion disorders. The formation of non-canonical structures,
      such as hairpin structures with X-X mismatches, has been proposed to affect gene
      expression and regulation, which are important in pathological studies of these
      devastating neurological diseases. However, little information is available
      regarding the thermodynamics of the repeat sequence under crowded cellular
      conditions where many non-canonical structures such as G-quadruplexes are highly
      stabilized, while duplexes are destabilised. In this study, we investigated the
      different stabilities of X-X mismatches in the context of internal d(CXG) self
      complementary sequences in an environment with a high concentration of cosolutes
      to mimic the crowding conditions in cells. The stabilities of full-matched
      duplexes and duplexes with A-A, G-G, and T-T mismatched base pairs under
      molecular crowding conditions were notably decreased compared to under dilute
      conditions. However, the stability of the DNA duplex with a C-C mismatch base
      pair was only slightly destabilised. Investigating different stabilities of X-X
      mismatches in d(CXG) sequences is important for improving our understanding of
      the formation and transition of multiple non-canonical structures in
      trinucleotide repeat diseases, and may provide insights for pathological studies
      and drug development.

PMID- 29339158
TI  - Myosin XI localizes at the mitotic spindle and along the cell plate during plant
      cell division in Physcomitrella patens.
AB  - Cell division is a fundamental biological process that has been extensively
      investigated in different systems. Similar to most eukaryotic cells, plant cells
      assemble a mitotic spindle to separate replicated chromosomes. In contrast, to
      complete cell division, plant cells assemble a phragmoplast, which is composed of
      aligned microtubules and actin filaments. This structure helps transport vesicles
      containing new cell wall material, which then fuse to form the cell plate; the
      cell plate will expand to create the new dividing cell wall. Because vesicles are
      known to be transported by myosin motors during interphase, we hypothesized this
      could also be the case during cell division and we investigated the localization
      of the plant homologue of myosin V - myosin XI, in cell division. In this work,
      we used the protonemal cells of the moss Physcomitrella patens as a model,
      because of its simple cellular morphology and ease to generate transgenic cell
      lines expressing fluorescent tagged proteins. Using a fluorescent protein fusion
      of myosin XI, we found that, during mitosis, this molecule appears to associate
      with the kinetochores immediately after nuclear envelope breakdown. Following
      metaphase, myosin XI stays associated with the spindle's midzone during the rest
      of mitosis, and when the phragmoplast is formed, it concentrates at the cell
      plate. Using an actin polymerization inhibitor, latrunculin B, we found that the
      association of myosin XI with the mitotic spindle and the phragmoplast are only
      partially dependent on the presence of filamentous actin. We also showed that
      myosin XI on the spindle partially overlaps with a v-SNARE vesicle marker but is
      not co-localized with the endoplasmic reticulum and a RabA vesicle marker. These
      observations suggest an actin-dependent and an actin-independent behavior of
      myosin XI during cell division, and provide novel insights to our understanding
      of the function of myosin XI during plant cell division.

PMID- 29339159
TI  - Analysis of the interactions between GMF and Arp2/3 complex in two binding sites
      by molecular dynamics simulation.
AB  - The Arp2/3 complex plays a key role in nucleating actin filaments branching. The
      glia maturation factor (GMF) competes with activators for interacting with the
      Arp2/3 complex and initiates the debranching of actin filaments. In this study,
      we performed a comparative analysis of interactions between GMF and the Arp2/3
      complex and identified new amino acid residues involved in GMF binding to the
      Arp2/3 complex at two separate sites, revealed by X-ray and single particle EM
      techniques. Using molecular dynamics simulations we demonstrated the quantitative
      and qualitative changes in hydrogen bonds upon binding with GMF. We identified
      the specific amino acid residues in GMF and Arp2/3 complex that stabilize the
      interactions and estimated the mean force profile for the GMF using umbrella
      sampling. Phylogenetic and structural analyses of the recently defined GMF
      binding site on the Arp3 subunit indicate a new mechanism for Arp2/3 complex
      inactivation that involves interactions between the Arp2/3 complex and GMF at two
      binding sites.

PMID- 29339160
TI  - Overstretching partially alkyne functionalized dsDNA using near infrared optical
      tweezers.
AB  - The force-extension behaviour of synthesized double-stranded DNAs (dsDNAs)
      designed to have 2.1% or 6.6% of the thymine bases alkyne functionalized was
      studied using near infrared (NIR) optical tweezers. Measurements were carried out
      on substrates with and without flurophores covalently attached to the alkyne
      moiety over an extended force range (F=0-70 pN) and results were compared to
      those obtained from an unmodified control. In accordance with earlier work [1]
      (measured over a force range F=0-5 pN), the force-extension of the dsDNA
      containing 2.1% modified-bases agreed well with that of the control. By contrast,
      the force-extension of the dsDNA containing 6.6% modified-bases showed an
      increasing deviation from that of the control as the dsDNA extension approached
      the molecule's contour length. These results indicate that incorporating alkyne
      functionalized bases can modify the mechanical properties of the dsDNA and that
      degree of functionalization should be carefully considered if a fluorescent
      mechanical analogue is required. A discrepancy between 1) the control dsDNA force
      extension measured in Ref. [1] and that measured here and 2) dsDNA extensions
      carried out on the same duplex at different laser powers was noted; this was
      attributed to beam heating by the NIR trapping laser which was estimated to raise
      the local temperature at the optical traps by DeltaT~10-15 degrees C.

PMID- 29339162
TI  - A method to improve prediction of secondary structure for large single RNA
      sequences.
AB  - The function of a particular RNA molecule within an organic system is principally
      determined by its structure. The current physical methods available for structure
      determination are time consuming and expensive. Hence, computational methods for
      structure prediction are often used. The prediction of the structure of a large
      single sequence of RNA needs a lot of research work. In the present work, a
      method is introduced to improve the prediction of large single sequence RNA
      secondary structure obtained by Mfold program using the concept of minimum free
      energy. The Mfold program contains a constraint option that allows forcing some
      helices in the predicted structure. In our method, some of the firstly formed
      hairpins that are expected, by a statistical study, to be present in the real
      structure are forced in the Mfold predicted structure. The results show
      improvement, toward the real structure, in the Mfold predicted structure and this
      gives evidence to the RNA kinetic folding.

PMID- 29339161
TI  - A new genetically engineered mouse model of choroid plexus carcinoma.
AB  - Choroid plexus carcinomas (CPCs) are highly malignant brain tumours predominantly
      found in children and associated to poor prognosis. Improved therapy for these
      cancers would benefit from the generation of animal models. Here we have created
      a novel mouse CPC model by expressing a stabilised form of c-Myc (MycT58A) and
      inactivating Trp53 in the choroid plexus of newborn mice. This induced aberrant
      proliferation of choroid plexus epithelial cells, leading to aggressive tumour
      development and death within 150 days. Choroid plexus tumours occurred with a
      complete penetrance in all brain ventricles, with prevalence in the lateral and
      fourth ventricles. Histological and cellular analysis indicated that these
      tumours were CPCs resembling their human counterparts. Comparison of gene
      expression profiles of CPCs and non-neoplastic tissues revealed profound
      alterations in cell cycle regulation and DNA damage responses, suggesting that
      dysregulation of cell division and DNA checkpoint pathways may represent key
      vulnerabilities. This novel animal model of CPC provides an invaluable tool to
      elucidate the mechanism of CPC formation and to develop successful therapies
      against this devastating paediatric cancer.

PMID- 29339163
TI  - Early process development of API applied to poorly water-soluble TBID.
AB  - Finding and optimising of synthesis processes for active pharmaceutical
      ingredients (API) is time consuming. In the finding phase, established methods
      for synthesis, purification and formulation are used to achieve a high purity API
      for biological studies. For promising API candidates, this is followed by pre
      clinical and clinical studies requiring sufficient quantities of the active
      component. Ideally, these should be produced with a process representative for a
      later production process and suitable for scaling to production capacity. This
      work presents an overview of different approaches for process synthesis based on
      an existing lab protocol. This is demonstrated for the production of the model
      drug 4,5,6,7-tetrabromo-2-(1H-imidazol-2-yl) isoindolin-1,3-dione (TBID). Early
      batch synthesis and purification procedures typically suffer from low and
      fluctuating yields and purities due to poor process control. In a first step the
      literature synthesis and purification procedure was modified and optimized using
      solubility measurements, targeting easier and safer processing for consecutive
      studies.

PMID- 29339164
TI  - NANOS2 acts as an intrinsic regulator of gonocytes-to-spermatogonia transition in
      the murine testes.
AB  - In the male mouse embryos, the primordial germ cells colonize the developing
      testes at E11.5. These resident germ cells termed gonocytes are the predecessors
      of spermatogonial stem cells (SSCs) and differentiating spermatogonia. Both of
      which are essential for male fertility where the former maintains the continuity
      of spermatogenesis and the latter generates pioneering waves of spermatozoa.
      Therefore the timely initiation of gonocytes-to-spermatogonia transition (GST) is
      an important process during which the cell fates of gonocytes might be
      segregated. However, it is unknown whether gonocytes are composed of a
      heterogeneous mixture of germ cells with distinct differentiation potentials
      during GST. Here, we find that gonocytes exhibit heterogeneity in terms of the
      expression pattern of at least three early spermatogonial marker genes namely
      Nanos2, Stra8 and Gfra1. NANOS2 expression levels are negatively correlated with
      those of STRA8 and GFRA1 before GST, while positive correlation with GFRA1 is
      established after GST. We further find that overexpression of NANOS2 results in
      the repression of GFRA1 and PLZF in gonocytes, leading to a delay in GST. On the
      other hand, loss of NANOS2 results in the up-regulation of GFRA1 and PLZF,
      indicating a precocious entry of GST. Taken together, our data suggest that
      NANOS2 functions as an intrinsic timekeeper of GST in the mouse testes.

PMID- 29339165
TI  - Safety and Efficacy of Transcatheter Left Atrial Appendage Closure for Stroke
      Prevention in Patients with Atrial Fibrillation.
AB  - Atrial Fibrillation (AF) is associated with a substantial risk of thromboembolic
      stroke. Although long-term treatment with warfarin or the non-vitamin K oral
      anticoagulants can reduce this risk, such therapy is underutilized, and safe and
      consistent long-term treatment can be challenging. Transcatheter left atrial
      appendage (LAA) closure is an emerging alternative to long-term oral
      anticoagulation. Long-term follow-up of randomized clinical trials demonstrate
      that Watchman LAA closure provides significant reductions in hemorrhagic stroke,
      cardiovascular death, and all-cause mortality compared with continued warfarin
      therapy. Major bleeding is also reduced compared with continued warfarin therapy
      once the post-implant pharmacologic regimen is completed. This review summarizes
      the current dataset for the safety and efficacy of transcatheter LAA closure, and
      highlights the gaps in evidence and future directions for clinical research.

PMID- 29339166
TI  - Anticoagulation in Acute Coronary Syndrome-State of the Art.
AB  - Early intravenous anticoagulation is the corner stone treatment of patients
      admitted with an acute coronary syndrome: it antagonizes the ongoing coronary
      thrombosis and facilitates the percutaneous coronary intervention, hence a
      reduction of mortality and acute stent thrombosis. Unfractionated heparin,
      enoxaparin, bivalirudin and fondaparinux have been extensively studied in large
      randomized control trials and meta-analyses with the same objective: reducing the
      ischemic burden without hiking hemorrhagic events. This conundrum is evolving
      along the generalization of the radial-artery access, the use of potent P2Y12 and
      the trend towards a tailored approach regarding the ischemic and bleeding
      balance. In this systematic review, we aimed at presenting the evidence based
      data and strategies for each anticoagulant in the setting of acute coronary
      syndrome with and without ST-segment elevation.

PMID- 29339167
TI  - Comparison of Anticoagulant Therapy for Atrial Fibrillation - Novel Oral
      Anticoagulants Versus Vitamin K Antagonists.
AB  - In patients with non-valvular atrial fibrillation (NVAF), oral anticoagulation is
      important for prevention of stroke and systemic embolism (SE). While Vitamin K
      antagonists (VKAs) have historically been the standard of care, these medications
      are limited by numerous food and drug interactions with onerous requirements for
      frequent monitoring and dose adjustments. Over the past decade, several novel
      oral anticoagulants (NOACs) have been developed to directly inhibit factor
      IIa/thrombin (dabigatran) or activated factor X (apixaban, rivaroxaban,
      edoxaban). These medications have been shown to be at least as effective as
      warfarin for stroke prevention in NVAF with more favorable safety profiles.
      However, their advantages are underscored by a lack of specific antidotes and
      assays quantifying their anticoagulant effects. This paper addresses the use of
      NOACs compared to VKAs in patients with NVAF, with a special focus on high-risk
      populations, including the elderly, those with renal disease, diabetes mellitus,
      coronary artery disease, and previous stroke. The current literature surrounding
      special clinical scenarios including the treatment of bleeding, perioperative
      management, and the use of NOACs in cardioversion and catheter ablation will be
      also discussed.

PMID- 29339168
TI  - Selection of P2Y12 Inhibitor in Percutaneous Coronary Intervention and/or Acute
      Coronary Syndrome.
AB  - The P2Y12 receptor plays a critical role in the amplification of platelet
      aggregation in response to various agonists and stable thrombus generation at the
      site of vascular injury leading to deleterious ischemic complications. Therefore,
      treatment with a P2Y12 receptor blocker is a major effective strategy to prevent
      ischemic complications in high-risk patients with acute coronary syndrome (ACS)
      and patients undergoing percutaneous coronary intervention (PCI). The
      determination of optimal platelet inhibition is based on maximizing
      antithrombotic properties while minimizing bleeding risk and is critically
      dependent on individual patient's propensity for thrombotic and bleeding risks.
      Immediately after ACS and during PCI, where highly elevated thrombotic activity
      is present, a loading dose administration with a potent P2Y12 receptor blocker
      such as ticagrelor or prasugrel is preferred. In stable coronary artery disease
      patients undergoing PCI, clopidogrel is widely used. In addition, in patients
      with ST-segment elevation myocardial infraction who cannot take oral medications,
      a fast acting intravenous glycoprotein IIb/IIIa inhibitor or P2Y12 receptor
      blocker, cangrelor, may add clinical benefits. During long term therapy, a
      strategy that prevents ischemic risk while avoiding excessive bleeding risk is
      similarly desired. Although up to one year dual antiplatelet therapy (DAPT) is
      recommended in patients undergoing elective stenting, the available data support
      the anti-ischemic benefit of prolonged DAPT (more than1 year) in patients with
      prior MI. In addition to the DAPT risk calculator tool, future risk assessment
      methods that analyze intrinsic thrombogenicity and atherosclerotic coronary
      burden may further identify the optimal candidate for prolonged DAPT to improve
      net clinical outcomes.

PMID- 29339169
TI  - The Timing of P2Y12 Inhibitor Initiation in the Treatment of ACS? Does the
      Evidence Exist in This Era?
AB  - The majority of acute coronary syndromes (ACS) are well characterized as a
      consequence of plaque rupture and subsequent thrombosis. Antiplatelet agents
      targeting inhibition of P2Y12 receptors on the platelets have been shown to
      reduce future risk of cardiovascular events in this patient population. However,
      the timing of initiation of these agents, in particular, in patients managed with
      an invasive strategy with percutaneous coronary interventions (PCI) is debatable.
      The data supporting pretreatment with antiplatelet agents prior to PCI in ACS
      patients date to trials performed >15 years ago, wherein the time to PCI was >5
      days, and hence, the utility of pretreatment with these agents in the
      contemporary era remains uncertain. In addition, newer antiplatelet agents such
      as prasugrel, ticagrelor, and cangrelor with rapid onset of action, pose a
      challenge for justification of oral antiplatelet pretreatment in patients with
      ACS. In this review article, we will discuss the pharmacokinetic properties of
      four different antiplatelet agents (clopidogrel, prasugrel, ticagrelor,
      cangrelor), as well as major randomized clinical trials assessing safety and
      efficacy of their role as pretreatment agents in patients presenting with ACS.

PMID- 29339170
TI  - Sub-anesthetic doses of ketamine attenuate nicotine self-administration in rats.
AB  - Smoking cessation strategies are of prime medical importance. Despite
      availability of various pharmacological agents in combating addiction to
      nicotine, more effective medications are needed. Based on recent findings, the
      glutamatergic system in the brain may provide novel targets. Here, we evaluated
      the effects of acute administration of sub-anesthetic doses of ketamine, an NMDA
      receptor antagonist, in both male and female Sprague-Dawley rats trained to self
      administer nicotine. Animals were injected subcutaneously with 5, 7.5 and 10
      mg/kg ketamine or saline and the effects on the number of intravenous nicotine
      infusions during a 45 min session was measured. Ketamine treatment significantly
      reduced nicotine self-administration in a dose-dependent manner. Moreover, a
      differential sensitivity between the sexes was observed as male rats responded to
      a lower dose of ketamine and with higher magnitude of effect than female rats. It
      is concluded that glutamatergic receptor manipulations may offer a novel and
      potentially sex-dependent intervention in nicotine addiction.

PMID- 29339171
TI  - DNA methylation level of the neprilysin promoter in Alzheimer's disease brains.
AB  - Neprilysin (NEP), a membrane-bound metalloprotease, has been shown to play an
      essential role in the clearance of amyloid beta (Abeta) peptides. Previous
      studies have reported that NEP expression is downregulated in the normal aging
      brain as well as in the Alzheimer's disease (AD) brain, providing evidence that
      the downregulation of NEP expression contributes to the age-dependent deposition
      of Abeta-containing plaques, a pathological hallmark of AD. However, the
      mechanisms underlying the downregulation remain unclear. In this study, we
      explored the relationship between DNA methylation status of CpG islands in the
      NEP promoter and its expression level in AD brains. We performed pyrosequencing
      analyses to detect the DNA methylation level in 31 postmortem AD brains and 40
      normal control brains. All 30 CpG sites showed no clear difference in methylation
      level. To further focus on methylation changes specific to neuronal cells, we
      performed methylation array experiments using neuronal nuclei from postmortem
      brains and found no clear difference in the methylation level between AD and
      normal control samples. Our detailed analyses, with a substantial number of brain
      samples, provide the first convincing evidence that DNA methylation of the NEP
      promoter is not involved in AD development and progression.

PMID- 29339172
TI  - Self-relevant processing of stranger's name in Chinese society: Surname matters.
AB  - Stimuli that have been frequently used to induce self-relevant processing are
      highly familiar to individuals (e.g., self-name [SN] and self-face). One's
      surname is an important form of collective self-concept; it represents the line
      of ancestry, and is psychologically salient. According to this concept, a
      stranger with the same surname may also elicit salient self-relevant processing,
      despite unfamiliarity; however, this has not yet been directly investigated. The
      present study adopted a three-stimulus oddball paradigm and multimodal
      electroencephalography to study the potential self-relevant processing of such
      stimuli. Behavioral results indicated that same-surname unfamiliar (SSU) names
      were rated more self-relevant than different-surname unfamiliar (DSU) names,
      although they were rated equally unfamiliar to subjects. Analysis of EEG data
      showed similar P2 enhancement in response to SN and SSU when compared to DSU. In
      contrast, the self-relevant effect on P3 amplitudes and theta synchronization
      decreased linearly from SN, SSU, to DSU conditions. Thus, both the behavioral and
      electrophysiological data indicate that unfamiliar names with the same surname
      can evoke reliable self-relevant processing.

PMID- 29339173
TI  - Neuroprotective effects of topiramate and memantine in combination with
      hypothermia in hypoxic-ischemic brain injury in vitro and in vivo.
AB  - Hypoxic-ischemic encephalopathy (HIE) is a major cause of perinatal mortality and
      subsequent severe neurological sequelae. Mild hypothermia is a standard therapy
      for HIE, but is used only in selected Reference Centers and in neonates >1800 g.
      Since neuronal death following HIE occurs by a cascade of events triggered by
      activation of glutamate receptors, we used in vitro and in vivo models of HIE to
      examine whether the AMPA/kainate receptor antagonist topiramate and the NMDA
      receptor antagonist memantine could exert neuroprotective effects, alone or in
      combination with hypothermia. For the in vitro experiments, rat organotypic
      hippocampal slices were exposed to a 30 min duration of oxygen-glucose
      deprivation (OGD): treatment with topiramate (1 MUM) and memantine (10-30 MUM) or
      hypothermia (35  degrees C or 32  degrees C) significantly attenuated CA1 damage
      after 24 h. The combination of hypothermia with topiramate and memantine enhanced
      their protective effect. For the in vivo experiments, we used 7 day-old rat pups
      subjected to permanent left common carotid artery occlusion followed by 120 min
      of hypoxia. Administration of topiramate or memantine (i.p., 20 mg/kg)
      immediately and 2 h after hypoxia or exposure to hypothermia (32  degrees C for 4
      h beginning 1 h after hypoxia) significantly reduced the extent of the resulting
      infarct. The combination of topiramate or memantine with hypothermia elicited a
      reduction of the infarct that was greater than that produced by drugs or
      hypothermia alone. Notably, memantine displayed a higher degree of
      neuroprotection as compared to topiramate both in vitro and in vivo and, when
      used alone at 20 mg/kg in vivo, produced a greater reduction in brain damage than
      observed using topiramate in combination with hypothermia. These results suggest
      that memantine may be more advantageous than topiramate as a therapeutic agent in
      neonates with HIE treated with hypothermia.

PMID- 29339174
TI  - The impact of strabismus surgery on gait pattern in patients with congenital or
      starting within one year of age strabismus.
AB  - Strabismus is a common visual disorder that negatively affects walking and
      balance. Therapeutic interventions for strabismus include strabismus surgery. Few
      studies investigated the relationship between strabismus surgery and postural
      control while, to the best of our knowledge, none has been conducted to assess
      the influence of strabismus surgery on gait. Therefore, the aim of this study was
      to evaluate the locomotion characteristics over patients with congenital or
      starting within one year of age strabismus, one month and three months after
      strabismus surgery. We enrolled 17 patients with a number of motor and sensorial
      features. Patients underwent an orthoptic and ophthalmological evaluation as well
      as a biomechanical evaluation before (T0) and after strabismus surgery (T1 at 1
      month, and T2 at 3 months). We observed, mostly in T2 evaluation, significant
      improvements in the spatio-temporal parameters, such as cadence, velocity, swing,
      stance and double support phases, step and stride length. The kinematic results
      revealed a significant increase in hip ROM, strongly related to the improvement
      of gait speed. No significant differences has been observed in knee and ankle
      joint ROM. The kinetic results revealed a significant increase in the maximum
      moment at the knee and ankle joints associated with an increase in the maximum
      ankle power. Our findings suggest that the safety and balance control associated
      with gait improve in patients with strabismus following surgery.

PMID- 29339175
TI  - Primary thymic adenocarcinomas: a clinicopathological and immunohistochemical
      study of 16 cases with emphasis on the morphological spectrum of differentiation.
AB  - Sixteen cases of primary thymic adenocarcinoma are presented. The patients are 9
      men and 7 women between the ages of 22 and 68 years (average, 45 years) who
      presented with non-specific symptoms including cough, chest pain, and dyspnea.
      Diagnostic imaging revealed the presence of an anterior mediastinal mass, which
      was surgically removed in all of the patients. Histologically, none of the tumors
      was encapsulated and showed different growth patterns including mucinous, non
      mucinous, and papillary features. The majority of cases showed mixed growth
      pattern, and the tumor was limited to the mediastinum with only a few cases
      extending to lymph nodes or pericardium. In two cases, the adenocarcinoma was
      associated with a thymoma. Immunohistochemical stains were performed, and their
      positive staining varied depending on the histology of the tumors, showing
      positive staining in some cases for keratin 7, keratin 20, CEA, CD5, CD117, and
      CDX-2. PAX8 and TTF-1 were negative in all the tumors. Follow-up information was
      obtained in 10 patients over a period of 1 to 12 years, indicating that three
      patients had died within a period of 14 months, one with brain metastasis, while
      seven patients have remained alive without recurrence. The cases herein described
      span the spectrum of thymic epithelial tumors and highlight the importance of
      recognizing this particular type of carcinoma, as it may follow a different
      outcome and require different treatment options.

PMID- 29339176
TI  - The absence of class III beta-tubulin is predictive of a favorable response to
      nab-paclitaxel and gemcitabine in patients with unresectable pancreatic ductal
      adenocarcinoma.
AB  - The combined administration of nab-paclitaxel and gemcitabine (nab-P + Gem) is a
      standard chemotherapy for unresectable pancreatic ductal adenocarcinoma (UR
      PDAC); thus, a predictive biomarker to identify patients best suited for nab-P +
      Gem therapy would be useful. Class III beta-tubulin (TUBB3) has been reported to
      be a predictive marker for taxane resistance in various tumors. However, the
      correlation between TUBB3 expression and the response to nab-P + Gem in patients
      with UR-PDAC has not been evaluated. We retrospectively reviewed 75 patients with
      UR-PDAC who received nab-P + Gem. TUBB3 expression was examined
      immunohistochemically in specimens obtained by endoscopic ultrasound-guided fine
      needle aspiration (EUS-FNA). From 67 analyzable specimens that were available for
      TUBB3 staining, 14 (21%) were negative for TUBB3 immunostaining and 53 (79%) were
      positive. Patients with negative TUBB3 expression showed a significantly higher
      disease control rate (100% vs. 64.2%; P = .008) and longer progression-free
      survival (PFS); (7.1 months vs. 3.7 months; log-rank test, P = .036) than those
      of patients with positive. Furthermore, negative TUBB3 expression was an
      independent predictive marker of a prolonged PFS on multivariate analysis (hazard
      ratio, 2.41; 95% confidence interval, 1.11-5.24; P = .026). Our data indicate
      that an absence of TUBB3 expression in specimens obtained by EUS-FNA may be a
      favorable predictive marker of the response to nab-P + Gem in patients with UR
      PDAC, highlighting its use as a potential new biomarker for treatment
      optimization.

PMID- 29339177
TI  - Trends in reporting histological subtyping of renal cell carcinoma: association
      with cancer center type.
AB  - Histological classification of renal cell carcinoma (RCC) has become increasingly
      important for clinical management. We identified 295483 RCC diagnosed from 1998
      2014 in the National Cancer Database (NCDB) to examine temporal trends in
      proportions of RCC with unspecified histology and several specific histologies
      from the 1998 and 2004 World Health Organization classifications of RCC. Further,
      multivariable log binomial analysis of 101062 RCC diagnosed from 2010 to 2014 was
      used to determine whether the association of diagnosing/treating facility type
      and the proportion of unspecified RCC is independent of patient demographic and
      clinical factors. Between 1998 and 2014, the proportion of histologically
      unspecified RCC decreased substantially in all facility types, with the decrease
      smallest in community programs (from 86.0% to 28.1%) and largest in National
      Cancer Institute-designated centers (from 85.1% to 9.8%). These decreases were
      offset by increases in percentages of papillary, clear cell, and chromophobe RCC
      cases. During 2010 to 2014, relative to community programs, RCCs were 21% less
      likely to be reported as unspecified histology (adjusted prevalence ratio [aPR] =
      0.79; 95% CI, 0.68-0.92) in comprehensive community programs, 32% less likely in
      integrated network programs (aPR = 0.68; 95% CI, 0.57-0.92) and academic programs
      (aPR = 0.68; 95% CI, 0.54-0.87), and 63% less likely (aPR = 0.37; 95% CI, 0.26
      0.52) in National Cancer Institute -designated programs. These results have
      implications for the optimal selection of targeted systemic therapies for
      patients with advanced disease, and for the potential value of cancer registry
      data in pathology quality improvement programs to promote more rapid and
      consistent adoption of new classifications of RCC and other neoplasms.

PMID- 29339178
TI  - The evolving diagnosis of noninvasive follicular thyroid neoplasm with papillary
      like nuclear features (NIFTP).

PMID- 29339179
TI  - Primary diffuse leptomeningeal atypical teratoid/rhabdoid tumor diagnosed by
      cerebrospinal fluid cytology: case report with molecular genetic analysis.
AB  - Atypical teratoid/rhabdoid tumors (AT/RT) are rare malignant neoplasms that
      mainly affect infants and young children, and are typically located in the
      cerebellar hemispheres. These tumors are histologically characterized by varying
      proportions of rhabdoid cells, and nuclear INI1 immunonegativity. Here, we report
      a case of a 15-year-old male with primary diffuse leptomeningeal AT/RT. The
      patient had symptoms similar to those of meningitis. Magnetic resonance imaging
      revealed leptomeningeal thickening. Cytological examination using cerebrospinal
      fluid was repeatedly performed and revealed rhabdoid cells with loss of INI1
      reactivity, and shortly after, the diagnosis of AT/RT was confirmed by tissue
      biopsy. Multiplex ligation-dependent probe amplification analysis revealed
      compound heterozygous microdeletion of the SMARCB1/INI1 locus. Leptomeningeal
      AT/RT without primary mass is extremely rare - only four cases have been
      previously reported to date. To the best of our knowledge, this is the first case
      report of primary leptomeningeal AT/RT with detailed genetic information.

PMID- 29339180
TI  - Leptin blocks the inhibitory effect of vitamin D on adipogenesis and cell
      proliferation in 3T3-L1 adipocytes.
AB  - Recently, we demonstrated high serum leptin and 25(OH)D (calcidiol) in obese
      animals, with high C/EBPbeta and PPARgamma expression in adipose tissue. Since
      the role of vitamin D in adipogenesis remains controversial and hyperleptinemia
      is found in obesity, we asked if leptin could interfere in vitamin D action on
      adipocytes. Here, we studied the direct effect of these two hormones upon 3T3L1
      preadipocytes incubated with or without 1,25(OH)2D (100 nM, 24 h) and with leptin
      (10-7 M, 4 h later). RT-PCR (VDR and Cyp27b1/1alpha-hydroxylase), western
      blotting (VDR, Cyp27b1/1alpha-hydroxylase, ObR-b, C/EBPbeta, PPARgamma and Bax
      content), a cell proliferation assay and an Annexin V-FITC binding assay were
      performed. Incubation with 1,25(OH)2D decreased Cyp27b1/1alpha-hydroxylase and
      VDR. Co-incubation of 1,25(OH)2D and leptin did not change Cyp27b1/1alpha
      hydroxylase and had no additive effect upon the decreased VDR mRNA. Incubation
      with 1,25(OH)2D decreased C/EBPbeta and PPARgamma. In the cell proliferation
      assay, 1,25(OH)2D decreased the number of 3T3L1 cells. No changes in OBR-b or
      apoptotic parameters (Bax and annexin-V) were observed. The 1,25(OH)2D decreased
      pro-adipogenic factors and proliferation of adipocytes. However, since it
      inhibits the conversion of 25(OH)D to 1,25(OH)2D and VDR mRNA long-term, it could
      decrease the vitamin D response in adipocytes, leading to greater adipogenesis.
      The co-incubation of both hormones, simulating what occurs in obesity, even
      neutralizing the effect on Cyp27b1/1alpha-hydroxylase, did not change the vitamin
      D sensitivity but decreased SOCS-3 and pSTAT-3. Thus, an excess of vitamin D and
      hyperleptinemia could decrease vitamin D sensitivity in adipocytes, contributing
      to increased adipogenesis.

PMID- 29339181
TI  - Effects of age on growth in Atlantic bluefin tuna (Thunnus thynnus).
AB  - Atlantic Bluefin Tuna Thunnus thynnus (ABFT) is considered one of the most
      important socio-economic species but there is a lack of information on the
      physiological and molecular processes regulating its growth and metabolism. In
      the present study, we focused on key molecules involved in growth process. The
      aim of the present study was to associate molecular markers related to growth
      with canonical procedures like morphological measurements such as curved fork
      length (CFL) and round weight (RWT). The ABFT specimens (n = 41) were organized
      into three different groups A, B and C according to their age. The molecular
      analysis of liver samples revealed that igf1, igf1r and mTOR genes, involved in
      growth process, were differentially expressed in relation to the age of the fish.
      In addition, during the analyzed period, faster growth was evident from 5 to 8
      years of age, after that, the growth rate decreased in terms of length yet
      increased in terms of adipose tissue storage, as supported by the higher fat
      content in the liver. These results are useful in expanding basic knowledge about
      the metabolic system of ABFT and provide new knowledge for the aquaculture
      industry.

PMID- 29339182
TI  - Interrelationship among annual cycles of sex steroids, corticosterone and body
      condition in Nyctibatrachus humayuni.
AB  - Synergism between extrinsic and intrinsic factors is crucial for the seasonality
      of reproduction. Environmental factors such as photoperiod and temperature
      activate the hypothalamus-pituitary-gonadal axis leading to the secretion of
      steroid hormones that are crucial for reproduction. Sex steroids are not only
      essential for the maturation of gonads, but also for development of secondary
      sexual characters in males and reproductive behaviour of both the sexes. In the
      present study, we quantified the urinary testosterone (UTM) and corticosterone
      (UCM) metabolites in males and urinary estradiol metabolites (UEM) and UCM in
      females of Nyctibatrachus humayuni for two consecutive years to determine annual
      and seasonal variation in the levels of sex steroids, corticosterone and body
      condition index (BCI). The results show that sex steroids were highest during the
      breeding season and lowest during the non-breeding season in both the sexes. An
      increase in UTM and UEM was observed in males and females respectively during the
      breeding season. Testicular histology showed the presence of all stages of
      spermatogenesis throughout the year indicating that spermatogenesis is
      potentially continuous. Ovarian histology showed the presence of vitellogenic
      follicles only during the breeding season indicating that oogenesis is strictly
      seasonal. In males, UCM levels were highest during the breeding season, while in
      females their levels were highest just prior to the breeding season. In males,
      BCI was highest during the pre-breeding season, declined during the breeding
      season to increase again during the post-breeding season. In females, BCI was
      comparable throughout the year. In males, UTM levels were positively correlated
      with UCM levels but negatively correlated with BCI. Interestingly, UEM, UCM and
      BCI were not correlated in females. These results indicate that N. humayuni
      exhibits an associated pattern of reproduction. Quantification of urinary
      progesterone metabolites (UPM) during the breeding season showed UPM levels were
      higher in post-spawning females, suggesting the significance of progesterone in
      ovulation. Further, non-invasive enzyme immunoassay has been successfully
      standardized in N. humayuni for the quantification of urinary metabolites of
      steroid hormones.

PMID- 29339183
TI  - Evolution of the growth hormone, prolactin, prolactin 2 and somatolactin family.
AB  - Growth hormone (GH), prolactin (PRL), prolactin 2 (PRL2) and somatolactin (SL)
      belong to the same hormone family and have a wide repertoire of effects including
      development, osmoregulation, metabolism and stimulation of growth. Both the
      hormone and the receptor family have been proposed to have expanded by gene
      duplications in early vertebrate evolution. A key question is how hormone
      receptor preferences have arisen among the duplicates. The first step to address
      this is to determine the time window for these duplications. Specifically, we
      aimed to see if duplications resulted from the two basal vertebrate
      tetraploidizations (1R and 2R). GH family genes from a broad range of vertebrate
      genomes were investigated using a combination of sequence-based phylogenetic
      analyses and comparisons of synteny. We conclude that the PRL and PRL2 genes
      arose from a common ancestor in 1R/2R, as shown by neighboring gene families. No
      other gene duplicates were preserved from these tetraploidization events. The
      ancestral genes that would give rise to GH and PRL/PRL2 arose from an earlier
      duplication; most likely a local gene duplication as they are syntenic in several
      species. Likewise, some evidence suggests that SL arose from a local duplication
      of an ancestral GH/SL gene in the same time window, explaining the lack of
      similarity in chromosomal neighbors to GH, PRL or PRL2. Thus, the basic triplet
      of ancestral GH, PRL/PRL2 and SL genes appear to be unexpectedly ancient.
      Following 1R/2R, only SL was duplicated in the teleost-specific tetraploidization
      3R, resulting in SLa and SLb. These time windows contrast with our recent report
      that the corresponding receptor genes GHR and PRLR arose through a local
      duplication in jawed vertebrates and that both receptor genes duplicated further
      in 3R, which reveals a surprising asynchrony in hormone and receptor gene
      duplications.

PMID- 29339184
TI  - A novel stress hormone response gene in tadpoles of Xenopus tropicalis.
AB  - Previous work identified a transcribed locus, Str. 34945, induced by the frog
      stress hormone corticosterone (CORT) in Xenopus tropicalis tails. Because thyroid
      hormone had no influence on its expression, Str. 34945 was dubbed the first "CORT
      only" gene known from tadpoles. Here, we examine the genomic annotation for this
      transcript, hormone specificity, time course of induction, tissue distribution,
      and developmental expression profile. The location of Str. 34945 on the X.
      tropicalis genome lies between the genes ush1g (Usher syndrome 1G) and fads6
      (fatty acid desaturase 6). A blast search showed that it maps to the same region
      on the X. laevis genome, but no hits were found in the human genome. Using RNA
      seq data and conventional reverse transcriptase PCR and sequencing, we show that
      Str. 34945 is part of the 3' untranslated region of ush1g. We find that CORT but
      not aldosterone or thyroid hormone treatment induces Str. 34945 in tadpole tails
      and that expression of Str. 34945 achieves maximal expression within 12-24 h of
      CORT treatment. Among tissues, Str. 34945 is induced to the highest degree in
      tail, with lesser induction in lungs, liver, and heart, and no induction in the
      brain or kidney. During natural metamorphosis, Str. 34945 expression in tails
      peaks at metamorphic climax. The role of ush1g in metamorphosis is not
      understood, but the specificity of its hormone response and its expression in
      tail make ush1g valuable as a marker of CORT-response gene induction independent
      of thyroid hormone.

PMID- 29339185
TI  - Dose-response relationship of tryptophan with large neutral amino acids, and its
      impact on physiological responses in the chick model.
AB  - Tryptophan (Trp) has been associated with the regulation of several behavioral
      and physiological processes, through stimulation of serotonergic activity.
      Tryptophan utilization at the metabolic level is influenced by the competitive
      carrier system it shares with large neutral amino acids (LNAA). This study was
      carried out using meat-type chicken as a model, to investigate the dose response
      effects of Trp/LNAA on fear response (tonic immobility; TI) and hormonal
      responses, including corticosterone (CORT), serotonin (5-HT), triiodothyronine
      (T3) and thyroxine (T4). A total of 12 cages (48 birds) were assigned to each of
      the six experimental groups at 29-42 days of age. Experimental diets were
      formulated to have incremental levels of Trp/LNAA (0.025, 0.030, 0.035, 0.040,
      0.045, and 0.050). The results revealed that, Trp/NAA had no significant effect
      on growth performance and TI of the birds. However, elevation of Trp/LNAA was
      concurred with a linear reduction in CORT (P < .0001, r2 = 0.819) and linear
      increases in 5-HT (P < .0001, r2 = 0.945), T3 (P = .0003, r2 = 0.403) and T4 (P <
      .0001, r2 = 0.937) levels. In conclusion, the results from the current study
      demonstrated that, although incremental levels of Trp/LNAA did not affect bird
      growth performance or fearfulness, it increased 5-HT, T3 and T4, and decreased
      CORT levels in a linear dose-dependent manner. Manipulation of Trp feeding levels
      could be applied to manage stressful conditions in birds.

PMID- 29339186
TI  - Uptake and intracellular fate of cholera toxin subunit b-modified mesoporous
      silica nanoparticle-supported lipid bilayers (aka protocells) in motoneurons.
AB  - Cholera toxin B (CTB) modified mesoporous silica nanoparticle supported lipid
      bilayers (CTB-protocells) are a promising, customizable approach for targeting
      therapeutic cargo to motoneurons. In the present study, the endocytic mechanism
      and intracellular fate of CTB-protocells in motoneurons were examined to provide
      information for the development of therapeutic application and cargo delivery.
      Pharmacological inhibitors elucidated CTB-protocells endocytosis to be dependent
      on the integrity of lipid rafts and macropinocytosis. Using immunofluorescence
      techniques, live confocal and transmission electron microscopy, CTB-protocells
      were primarily found in the cytosol, membrane lipid domains and Golgi. There was
      no difference in the amount of motoneuron activity dependent uptake of CTB
      protocells in neuromuscular junctions, consistent with clathrin activation at the
      axon terminals during low frequency activity. In conclusion, CTB-protocells
      uptake is mediated principally by lipid rafts and macropinocytosis. Once
      internalized, CTB-protocells escape lysosomal degradation, and engage biological
      pathways that are not readily accessible by untargeted delivery methods.

PMID- 29339187
TI  - Doxorubicin-loaded dendritic-Fe3O4 supramolecular nanoparticles for magnetic drug
      targeting and tumor regression in spheroid murine melanoma model.
AB  - This work evaluates the magnetically-guided delivery of DOX-loaded dendritic
      Fe3O4 nanoparticles and their tumor regression efficacy in subcutaneous melanoma
      in C57BL/6 mice. The hematological, biochemical and histopathological parameters
      were minimally affected. The nanoparticles localized in lungs, liver and spleen
      suggesting non-specific uptake. However, in tumor-bearing mice, substantially
      higher localization in magnetically-targeted tumor was observed when compared to
      passive localization in non-targeted tumor. The animals of treated group showed
      significantly high iron levels (161 MUg of Fe/mg dry organ weight) in the tumor
      against the control (<25 MUg of Fe/mg dry organ weight). This high localization
      led to high concentrations of DOX in the tumor which not only induced significant
      tumor regression but also arrested further growth. Within 14 days, the average
      tumor volume was reduced to 55+/-8.3 mm3 (treated) as compared to 4794+/-844 mm3
      (control), i.e. ~88-fold decrease. The tumor disappeared by the end of 20th day
      post-treatment and ~100% survival rate was observed.

PMID- 29339188
TI  - The enhancement of siPLK1 penetration across BBB and its anti glioblastoma
      activity in vivo by magnet and transferrin co-modified nanoparticle.
AB  - In order to enhance the penetration of small interference RNA against the polo
      like kinase I (siPLK1) across BBB to treat glioblastoma (GBM), transferrin (Tf)
      modified magnetic nanoparticle (Tf-PEG-PLL/MNP@siPLK1) was prepared. The in vitro
      experiments indicated that Tf-PEG-PLL/MNP@siPLK1 enhanced the cellular uptake of
      siPLK1, which resulted in an increase of gene silencing effect and cytotoxicity
      of Tf-PEG-PLL/MNP@siPLK1 on U87 cells. Besides, Tf-PEG-PLL/MNP@siPLK1
      significantly inhibited the growth of U87 glioblastoma spheroids and markedly
      increased the BBB penetration efficiency of siPLK1 with the application of
      external magnetic field in in-vitro BBB model. The in vivo experiments indicated
      that siPLK1 selectively accumulated in the brain tissue, and markedly reduced
      tumor volume and prolonged the survival time of GBM-bearing mice after Tf-PEG
      PLL/MNP@siPLK1 was injected to GBM-bearing mice via tail vein. The above data
      indicated that magnet and transferrin co-modified nanoparticle enhanced siPLK1
      penetration across BBB and increased its anti GBM activity in vivo.

PMID- 29339189
TI  - Magnetic nanoparticles modified-porous scaffolds for bone regeneration and
      photothermal therapy against tumors.
AB  - For effectively treating tumor related-bone defects, design and fabrication of
      multifunctional biomaterials still remain a great challenge. Herein, we firstly
      fabricated magnetic SrFe12O19 nanoparticles modified-mesoporous bioglass
      (BG)/chitosan (CS) porous scaffold (MBCS) with excellent bone regeneration and
      antitumor function. The as-produced magnetic field from MBCS promoted the
      expression levels of osteogenic-related genes (OCN, COL1, Runx2 and ALP) and the
      new bone regeneration by activated BMP-2/Smad/Runx2 pathway. Moreover, the
      SrFe12O19 nanoparticles in MBCS improved the photothermal conversion property.
      Under the irradiation of near-infrared (NIR) laser, the elevated temperatures of
      tumors co-cultured with MBCS triggered tumor apoptosis and ablation. As compared
      with the pure scaffold group, MBCS/NIR group possessed the excellent antitumor
      efficacy against osteosarcoma via the hyperthermia ablation. Therefore, the
      multifunctional MBCS with excellent bone regeneration and photothermal therapy
      functions has a great application for treating the tumor-related bone defects.

PMID- 29339191
TI  - Current status and perspectives of fungal entomopathogens used for microbial
      control of arthropod pests in Brazil.
AB  - Entomopathogenic fungi play a central role in Brazil's biopesticide market.
      Approximately 50% of registered microbial biopesticides comprise mycoinsecticides
      and/or mycoacaricides consisting of hypocrealean fungi, with most based on
      Metarhizium anisopliae sensu stricto (s. str.) and Beauveria bassiana s. str.
      These fungi are mainly used to control spittlebugs in sugarcane fields and
      whiteflies in row crops, respectively, with annual applications surpassing three
      million hectares. Research also emphasizes the potential of fungal
      entomopathogens to manage arthropod vectors of human diseases. Most registered
      fungal formulations comprise wettable powders or technical (non-formulated)
      products, with relatively few new developments in formulation technology. Despite
      the large area treated with mycoinsecticides (i.e., approx. 2 million ha of
      sugarcane treated with M. anisopliae and 1.5 million ha of soybean treated with
      B. bassiana), their market share remains small compared with the chemical
      insecticide market. Nevertheless, several major agricultural companies are
      investing in fungus-based products with the aim at achieving more sustainable IPM
      programs for major pests in both organic and conventional crops. Government and
      private research groups are pursuing innovative technologies for mass production,
      formulation, product stability and quality control, which will support cost
      effective commercial mycoinsecticides. Here, we summarize the status of
      mycoinsecticides currently available in Brazil and discuss future prospects.

PMID- 29339192
TI  - Tissue specific differences in mitochondrial DNA maintenance and expression.
AB  - The different cell types of multicellular organisms have specialized
      physiological requirements, affecting also their mitochondrial energy production
      and metabolism. The genome of mitochondria is essential for mitochondrial
      oxidative phosphorylation (OXHPOS) and thus plays a central role in many human
      mitochondrial pathologies. Disorders affecting mitochondrial DNA (mtDNA)
      maintenance are typically resulting in a tissue-specific pattern of mtDNA
      deletions and rearrangements. Despite this role in disease as well as a biomarker
      of mitochondrial biogenesis, the tissue-specific parameters of mitochondrial DNA
      maintenance have been virtually unexplored. In the presented study, we
      investigated mtDNA replication, topology, gene expression and damage in six
      different tissues of adult mice and sought to correlate these with the levels of
      known protein factors involved in mtDNA replication and transcription. Our
      results show that while liver and kidney cells replicate their mtDNA using the
      asynchronous mechanism known from cultured cells, tissues with high OXPHOS
      activity, such as heart, brain, skeletal muscle and brown fat, employ a strand
      coupled replication mode, combined with increased levels of recombination. The
      strand-coupled replication mode correlated also with mtDNA damage levels,
      indicating that the replication mechanism represents a tissue-specific strategy
      to deal with intrinsic oxidative stress. While the preferred replication mode did
      not correlate with mtDNA transcription or the levels of most known mtDNA
      maintenance proteins, mtSSB was most abundant in tissues using strand
      asynchronous mechanism. Although mitochondrial transcripts were most abundant in
      tissues with high metabolic rate, the mtDNA copy number per tissue mass was
      remarkably similar in all tissues. We propose that the tissue-specific features
      of mtDNA maintenance are primarily driven by the intrinsic reactive oxygen
      species exposure, mediated by DNA repair factors, whose identity remains to be
      elucidated.

PMID- 29339193
TI  - A pilot study on the biomechanical assessment of obstructive sleep apnea pre and
      post bariatric surgery.
AB  - Obesity is a major risk factor for obstructive sleep apnea patients. In obese
      patients the severity of this risk can be reduced by bariatric surgery. This
      pilot study investigates the perioperative effects of bariatric surgery on
      obstructive sleep apnea and on the physical and biomechanical characteristics of
      the upper airway. Polysomnography and computer tomography data for 10 morbid
      obese patients promoted for bariatric surgery were conducted before surgery and
      at 6 and 12 months postoperatively for assessment of the oropharyngeal anatomy,
      and subsequent three-dimensional modelling of the airway. Mean values for the
      apnea/hypopnea index and body mass index significantly reduced after surgery. To
      combine the effect of changes in the upper airway volume and body mass index, a
      new volume body mass index is introduced. This index increases with a successful
      bariatric surgery. Although bariatric surgery leads to an effective weight
      reduction for all age groups, for obstructive sleep apnea patients it may be
      effective for middle age, less effective for 50-60 years, and further less
      effective for patients over the age of 60 years.

PMID- 29339190
TI  - Systemic and local toxicity of metal debris released from hip prostheses: A
      review of experimental approaches.
AB  - Despite the technological improvements in orthopedic joint replacement implants,
      wear and corrosion products associated with the metal components of these
      implants may result in adverse local tissue and perhaps systemic reactions and
      toxicities. The current review encompasses a literature review of the local and
      systemic toxicity studies concerning the effect of CoCrMo wear debris released
      from wear and corrosion of orthopedic implants and prostheses. Release of
      metallic debris is mainly in the form of micro- and nano-particles, ions of
      different valences, and oxides composed of Co and Cr. Though these substances
      alter human biology, their direct effects of these substances on specific tissue
      types remain poorly understood. This may partially be the consequence of the
      multivariate research methodologies employed, leading to inconsistent reports.
      This review proposes the importance of developing new and more appropriate in
      vitro methodologies to study the cellular responses and toxicity mediated by
      joint replacement wear debris in-vivo.

PMID- 29339195
TI  - All about the caspase-dependent functions without cell death.

PMID- 29339194
TI  - Vaginal Construction and Treatment Providers' Experiences: A Qualitative
      Analysis.
AB  - STUDY OBJECTIVE: To investigate specialist clinicians' experiences of treating
      vaginal agenesis. DESIGN: Semi-structured interviews. SETTING: Twelve hospitals
      in Britain and Sweden. PARTICIPANTS: Thirty-two health professionals connected to
      multidisciplinary teams (MDTs) including medical specialists and psychologists.
      INTERVENTIONS AND MAIN OUTCOME MEASURES: Theoretical thematic analysis of
      recorded verbatim data. RESULTS: The gynecologist and psychologist interviewees
      share certain observations including the importance of psychological readiness
      for and appropriate timing of treatment. Three overlapping themes are identified
      in our theoretical analysis of the MDT clinicians' talk: (1) the stigma of
      vaginal agenesis and the pressure to be "normal" can lead patients to minimize
      the time, effort, physical discomfort, and emotional cost inherent in treatment.
      (2) Under pressure, treatment might be presented to patients with insufficient
      attention to the potential psychological effect of the language used.
      Furthermore, the opportunity to question what is "normal" in sex is generally not
      taken up. It can be challenging to help the women to transcend their medicalized
      experiences to come to experiencing their bodies as sexual and enjoyable. (3) The
      reality of treatment demands, which are not always adequately processed before
      treatment, can lead to discontinuation and even disengagement with services.
      CONCLUSION: The MDT clinicians in this study emphasized the importance of
      psychological input in vaginal construction. However, such input should
      proactively question social norms about how women's genitalia should appear and
      function. Furthermore, rather than steering patients (back) to treatment, the
      entire MDT could more explicitly question social norms and help the women to do
      the same. By shifting the definition of success from anatomy to personal agency,
      the clinical focus is transformed from treatment to women.

PMID- 29339196
TI  - Coronary Arteriovenous Fistula in Continuity With the Aortic Arch.
AB  - Coronary arteriovenous fistula in continuity with the aortic arch by abnormal
      vessels running along the surface of the pulmonary artery is rare. We describe 2
      patients with this rare and unique arteriovenous network and discuss the issue of
      diagnosis and treatment with a review of the literature.

PMID- 29339197
TI  - Differential insulin and steroidogenic signaling in insulin resistant and non
      insulin resistant human luteinized granulosa cells-A study in PCOS patients.
AB  - Insulin resistance (IR) is one of the significant aberrations in polycystic
      ovarian syndrome (PCOS), however is only observed in 70%-80% of obese PCOS and
      20%-25% of lean PCOS. Hyperinsulinemia accompanies PCOS-IR along with
      hyperandrogenemia against normal insulin and androgen levels in PCOS-non insulin
      resistance (NIR). This could possibly be due to defects in the downstream
      signaling pathways. The study thus aims to unravel insulin and steroidogenic
      signaling pathways in luteinized granulosa cells isolated from PCOS-IR and NIR vs
      matched controls. Luteinized granulosa cells from 30 controls and 39 PCOS were
      classified for IR based on a novel method of down regulation of protein
      expression of insulin receptor-beta (INSR- beta) as shown in our previous paper.
      We evaluated expression of molecules involved in insulin, steroidogenic signaling
      and lipid metabolism in luteinized granulosa cells followed by analysis of
      estradiol, progesterone and testosterone in follicular fluid. Protein expression
      of INSR- beta, pIRS (ser 307), PI(3)K, PKC-zeta, pAkt, ERK1/2, pP38MAPK and gene
      expression of IGF showed differential expression in the two groups. Increased
      protein expression of PPAR-gamma was accompanied by up regulation in SREBP1c,
      FAS, CPT-1 and ACC-1 genes in PCOS-IR group. Expression of StAR, CYP19A1, 17 beta
      HSD and 3 beta- HSD demonstrated significant decrease along with increase in
      CYP11A1, FSH-R and LH-R in both the groups. Follicular fluid testosterone
      increased and progesterone decreased in PCOS-IR group. This study shows how
      candidate molecules that were differentially expressed, aid in designing targeted
      therapy against the two phenotypes of PCOS.

PMID- 29339198
TI  - CD90+ cardiac fibroblasts reduce fibrosis of acute myocardial injury in rats.
AB  - OBJECTIVE: To explore the differentiation tendency of CD90+ cardiac fibroblast
      (CFs) into cardiomyogenic cells in vitro and repair functions in acute myocardial
      infarction rats. METHODS: CD90+ subpopulation was sorted from rat CFs by flow
      cytometry. 10 MUmoL/L of 5-Azacytosine (5-aza) was used to induce differentiation
      of CFs into cardiomyogenic cells. An acute myocardial infarction model was
      prepared by ligation of the rat left anterior descending coronary artery. After
      nuclei were labeled by DAPI, induced CD90+ CFs were injected into the infarction
      marginal zone. Before coronary ligation, 40 min after ligation, and at 7 and 14
      days after cell transplantation, cardiac function changes were detected by
      ultrasound imaging system respectively. cTnT and endothelial cell marker VIII
      factor were detected by immunofluorescence staining. Infarct size was examined by
      TTC staining. Fibrosis was evaluated with masson's trichrome staining, vimentin,
      type I and type III collagen staining. RESULTS: CD90+ CFs sorted by flow
      cytometry was 34.9%. On day 28 after induction, the cTnT positive rate was 61.17
      +/- 9.75%. Left ventricular ejection fraction (LVEF) and left ventricular
      fractional shortening (LVFS) at days 7 and 14 after transplantation were
      significantly increased compared with those before transplantation (P < 0.05).
      LVEF and LVFS at the 14th day after transplantation were also significantly
      increased compared with those at the 7th day (LVEF: 61.40 +/- 2.45% vs. 56.25 +/-
      2.9%, LVFS: 33.21 +/- 0.68% vs. 30.26 +/- 2.06%, P < 0.01). Additionally, small
      numbers of CD90+ CFs differentiated into cardiomyocytes and became involved in
      neovascularization. CD90+ CFs and CFs reduced myocardial infarct size at days 14.
      It was significantly smaller in rats with CFs transplantation group than those in
      MI group(24.78 +/- 2.28% vs. 31.28 +/- 2.83%, P < 0.05), and it was also
      significantly smaller in rats with CD90+CFs transplantation group than those in
      CFs transplantation group (17.47 +/- 4.15% vs. 24.78 +/- 2.28%, P < 0.05).
      Meanwhile, The percentage of fibrotic area and vimentin, type I and type III
      collagen in the infarct border zone and infarct area were both significantly
      reduced in CD90 + CFs. CONCLUSION: CD90+ CFs is the preponderant subpopulation of
      cardiomyogenic differentiation, with potential use as seed cells in basic and
      clinical research of heart regeneration and repair.

PMID- 29339199
TI  - Neutralization of TNFR-1 and TNFR-2 modulates S. aureus induced septic arthritis
      by regulating the levels of pro inflammatory and anti inflammatory cytokines
      during the progression of the disease.
AB  - Staphylococcal septic arthritis remains a serious medical concern due to rapid
      and sustained production of inflammatory cytokines that leads to progressive and
      irreversible joint destruction with high mortality rate in patients despite
      adequate antibiotics treatment. TNF-alpha signalling via TNFR-1 contributes to
      arthritic destruction by aggravating inflammation. Impact of TNFR-2 signalling is
      not well established in this aspect. Hence the objective of our study was to
      evaluate the role of dual neutralization TNFR-1 and TNFR-2 in the pathogenesis of
      S. aureus infection induced septic arthritis. Mice were infected with live S.
      aureus (5 * 106 cells/ml) followed by administration of TNFR-1and TNFR-2
      neutralizing antibody. To measure arthritis index and osteoclastogenesis,
      histology result in joint tissue and TRAP staining images of arthritis joints
      have been performed respectively. Maximum reduction in the joint and paw swelling
      was observed in infected mice treated with both TNFR-1 and TNFR-2 antibody. NF
      kappaB signalling was found to be mainly regulated by TNFR-1 whereas TNFR-2
      significantly modulated JNK pathway. Lowest levels of inflammatory cytokines like
      TNF-alpha, IL-1beta, IL-6, and IFN-gamma were observed in both serum and synovial
      tissues signifying maximum protection in S. aureus arthritis during combination
      treatment. However IFN-gamma and IL-10 levels were significantly altered by TNFR
      2 neutralization that indicates both pro and anti inflammatory role of TNFR-2
      respectively. Highest decrement in ROS concentration, iNOS expression with least
      MPO and lysozyme activity was detected in case of combined neutralization. During
      the early phase of infection all the aforesaid inflammatory parameters remained
      elevated due to lack of IL-10 as a result of TNFR-2 neutralization as IL-10
      negatively modulates pro inflammatory cytokines. Increase in inflammatory
      cytokines during early phase might also be responsible for decreased bacterial
      count in TNFR-2 neutralized groups. Thus it can be suggested that combined
      administration of TNFR-1 and TNFR-2 antibody has a beneficial effect against the
      severity of S. aureus induced arthritis.

PMID- 29339200
TI  - Preventing healthcare-associated Gram-negative bloodstream infections.

PMID- 29339201
TI  - Laminar airflow system use across the operating surface for airborne infection
      prevention in office-based surgical procedures.

PMID- 29339202
TI  - An in-situ pilot study to investigate the native clinical resistance of enamel to
      erosion.
AB  - OBJECTIVES: To investigate the differences in susceptibility of the surface of
      native and polished enamel to dietary erosion using an in-situ model. METHODS:
      Thirty healthy volunteers (n = 10 per group) wore mandibular appliances
      containing 2 native and 2 polished enamel samples for 30 min after which, the
      samples were exposed to either an ex-vivo or in-vivo immersion in orange juice
      for 5, 10 or 15 min and the cycle repeated twice with an hour's interval between
      them. Samples were scanned with a non-contacting laser profilometer and surface
      roughness was extracted from the data, together with step height and
      microhardness change on the polished enamel samples. RESULTS: All volunteers
      completed the study. For native enamel there were no statistical difference
      between baseline roughness values versus post erosion. Polished enamel
      significantly increased mean (SD) Sa roughness from baseline for each group
      resulting in roughness change of 0.04 (0.03), 0.06 (0.04), 0.04 (0.03), 0.06
      (0.03), 0.08 (0.05) and 0.09 (0.05) MUm respectively. With statistical
      differences between roughness change 45 min in-vivo versus 45 min ex-vivo (p <
      0.05). Microhardness significantly decreased for each polished group, with
      statistical differences in hardness change between 30 min in-vivo versus 30 min
      ex-vivo (p < 0.05), 45 min in-vivo versus 30 min ex-vivo (p < 0.01), 45 min in
      vivo versus 45 min ex-vivo (p < 0.01). CONCLUSIONS: The native resistance to
      erosion provided clinically is a combination of the ultrastructure of outer
      enamel, protection from the salivary pellicle and the overall effects of the oral
      environment. CLINICALTRIALS. GOV IDENTIFIER: NCT03178968. CLINICAL SIGNIFICANCE:
      This study demonstrates that outer enamel is innately more resistant to erosion
      which is clinically relevant as once there has been structural breakdown at this
      level the effects of erosive wear will be accelerated.

PMID- 29339203
TI  - Clinical performance of full rehabilitations with direct composite in severe
      tooth wear patients: 3.5 Years results.
AB  - OBJECTIVES: To evaluate the mid-term clinical performance of direct composite
      restorations placed in patients with pathological tooth wear needing full
      rehabilitation with an increase of vertical dimension of occlusion. METHODS: In a
      prospective trial 34 patients (34.0 +/- 8.4 years; 25 males, 9 females) were
      treated with a minimal invasive additive technique using composite restorations.
      The restorative treatment protocol was to provide all teeth with composite build
      up restorations in an increased vertical dimension of occlusion (VDO) using the
      DSO-technique. Recall appointments were planned after 1 month, 1 and 3 years
      after treatment. Restorations were scored for clinically acceptability (FDI
      criteria) and scores 4 and 5 were recorded as clinically unacceptable.
      Frequencies of failures and Kaplan Meier survival curves are presented and effect
      of relevant variables was calculated with a multifactorial Cox regression (p <
      0.05). RESULTS: 1256 Restorations were placed, 687 anterior, 324 premolar, and
      245 molar restorations. After a mean observation time of 39.7 months a total of
      69 failures were observed, of which 61 restorations were repaired (score 4) and 8
      were replaced (score 5). Most common reasons for failure were (chip) fractures (n
      = 43) and caries (n = 11). Placement of anterior restorations in two sessions led
      to significant 4.6 times more failures then placed in one session. CONCLUSIONS:
      In patients with severe tooth wear a full rehabilitation, in an increased
      vertical dimension of occlusion, direct composite resin restorations show a 94.8%
      success and 99.3% survival rate after a period of 3.5 years.

PMID- 29339204
TI  - WITHDRAWN: Serum uric acid and prevalence of age-related hearing loss in the
      Japanese population: Baseline data from the Aidai Cohort Study in Yawatahama.
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- 29339205
TI  - Agreement of Musculoskeletal Ultrasound and Clinical Assessment of Shoulder
      Impairment in Manual Wheelchair Users With Various Duration of Spinal Cord
      Injury.
AB  - OBJECTIVES: To determine (1) agreement of musculoskeletal ultrasound (MSK-US)
      findings of shoulder pathology and related shoulder special test results in
      individuals with varied durations of manual wheelchair (MWC) use after spinal
      cord injury (SCI); and (2) whether shoulder musculoskeletal impairments, per MSK
      US and clinical examination, differed in individuals with SCI and varying
      durations of MWC use. DESIGN: Cross-sectional cohort study. SETTING: Laboratory
      setting. PARTICIPANTS: Adult volunteers (N=23) with SCI who used an MWC for
      community mobility. Individuals were stratified into 3 groups based on duration
      of MWC use: <5 years, 5 to 15 years, and >15 years. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: Special tests for shoulder impingement and
      bicipital tendonitis were performed. Bilateral shoulder MSK-US was performed,
      with the Ultrasound Shoulder Pathology Rating Scale (USPRS) quantifying biceps
      tendon, supraspinatus tendon, and greater tuberosity cortical surface
      impairments. RESULTS: No agreement was found between MSK-US and related special
      tests. Special tests failed to identify impairment in 33.3% to 100% of those
      identified on MSK-US. The total USPRS score was highest in those with >15 years'
      MWC use. A higher proportion of dynamic impingement (supraspinatus and biceps)
      was found in those with >15 years' MWC use, with other MSK-US items having
      moderate effect sizes among duration-use groups. CONCLUSIONS: MSK-US identified
      shoulder impairments more frequently than commonly used special tests. A
      significant increase in the presence of MSK-US shoulder impairments was
      identified in the longest-duration group. This was not the case for special tests
      or pain. MSK-US is an easily administered, low-cost, noninvasive method for
      determining shoulder impairments and should be used in routine screening of
      individuals who use an MWC after SCI.

PMID- 29339206
TI  - Objective Sleep Measures in Inpatients With Subacute Stroke Associated With
      Levels and Improvements in Activities of Daily Living.
AB  - OBJECTIVE: To investigate whether objective polysomnographic measures of
      prevalent sleep problems such as sleep-disordered-breathing (SDB) and insomnia
      are associated with activities of daily living levels in inpatients at
      rehabilitation units. DESIGN: Retrospective and observational study. SETTING:
      Single rehabilitation center. PARTICIPANTS: Inpatients with subacute stroke
      (N=123) (61.6+/-13.1 years; 23.8+/-3.4 kg/m2; 33% women; 90.5+/-36.7 days post
      stroke) underwent a 1-night polysomnographic study and a 1-month inpatient
      rehabilitation program. MAIN OUTCOME MEASURES: Admission and discharge Barthel
      Index (BI) scores and its change scores. RESULTS: One hundred three (92%)
      patients had moderate-to-severe SDB (46.7+/-25.1 events/h in the apnea-hypopnea
      index), and 24 (19.5%) patients had acceptable continuous positive airway
      pressure adherence. Diverse values were found for total sleep time (259+/-71
      min), sleep efficiency (69.5%+/-19.3%), sleep latency (24.3+/-30.9 min), and
      wakefulness after sleep onset (93.1+/-74.2 min). Admission BI scores and the BI
      change scores were 33.8+/-23.2 and 10.1+/-9.2, respectively. The National
      Institutes of Health Stroke Scale (NIHSS, 10.2+/-5.6), available in 57 (46%)
      patients, was negatively associated with admission levels and gains in BI change
      scores (P<.001, =0.002, respectively) in a univariate analysis. In regression
      models with backward selection, excluding NIHSS score, both age (P=.025) and
      wakefulness after sleep onset (P<.001) were negatively associated (adjusted
      R2=0.260) with admission BI scores. Comorbidity of hypertension; sleep latency
      percentage of stage 1, non-rapid eye movement sleep; and desaturation events >=4%
      (P<.001, 0.001, 0.021, and 0.043, respectively; adjusted R2=0.252) were
      negatively associated with BI score gains. CONCLUSIONS: Based on objective sleep
      measures, insomnia rather than SDB in inpatients with subacute stroke was
      associated negatively with admission levels of activity of daily living and its
      improvement after a 1-month rehabilitation course.

PMID- 29339207
TI  - Nicaraven reduces cancer metastasis to irradiated lungs by decreasing CCL8 and
      macrophage recruitment.
AB  - Radiotherapy for cancer patients damages normal tissues, thereby inducing an
      inflammatory response and promoting cancer metastasis. We investigated whether
      nicaraven, a compound with radioprotective and anti-inflammatory properties,
      could attenuate radiation-induced cancer metastasis to the lungs of mice.
      Nicaraven and amifostine, another commercial radioprotective agent, had limited
      effects on both the radiosensitivity of Lewis lung carcinoma cells in vitro and
      radiation-induced tumor growth inhibition in vivo. Using experimental and
      spontaneous metastasis models, we confirmed that thorax irradiation with 5 Gy X
      rays dramatically increased the number of tumors in the lungs. Interestingly, the
      number of tumors in the lungs was significantly reduced by administering
      nicaraven but not by administering amifostine daily after radiation exposure.
      Furthermore, nicaraven administration effectively inhibited CCL8 expression and
      macrophage recruitment in the lungs 1 day after thorax irradiation. Our data
      suggest that nicaraven attenuates radiation-induced lung metastasis, likely by
      regulating the inflammatory response after radiation exposure.

PMID- 29339208
TI  - Targeted shRNA-loaded liposome complex combined with focused ultrasound for blood
      brain barrier disruption and suppressing glioma growth.
AB  - Our previous studies have demonstrated that focused ultrasound (FUS) combined
      with DNA-loaded microbubbles (MBs) can induce noninvasive, reversible, local
      disruption of the blood brain barrier (BBB) and enable targeted exogenous gene
      transfer into the central nervous system. However, due to low gene loading or the
      absence of positive targeting, to date, there has been no therapeutic effect of
      MBs combined with FUS in tumor treatment. In the current study, we adopted a
      phospholipid complex that exhibited sufficient gene loading and peptide-mediated
      targeting to delay glioma growth. First, we bound MBs to shBirc5-lipo-NGR, which
      performed the dual function of tumor cell targeting and effective gene loading.
      Next, we demonstrated that FUS-aided MB-shBirc5-lipo-NGR exhibited a higher
      transfection efficiency compared with the control group. Finally, we evaluated
      the silencing effect of shBirc5 using an apoptosis assay, real time-polymerase
      chain reaction (PCR), western blotting (WB) in vitro and a volume measurement
      survival analysis in vivo. The experimental group exhibited a significant
      therapeutic effect, while the FUS-only, MB-shBirc5-lipo-NGR-only and FUS-aided MB
      shControl-lipo-NGR groups displayed no changes in tumor growth or survival time
      (P < .01). Consequently, our study indicated that MB-shBirc5-lipo-NGR combined
      with FUS is a promising new RNA interference technique for the treatment of
      glioma.

PMID- 29339209
TI  - Extratumoral PD-1 blockade does not perpetuate obesity-associated inflammation in
      esophageal adenocarcinoma.
AB  - Checkpoint inhibitors, such as anti-PD-1 (Programmed death-1), are transforming
      cancer treatment for inoperable or advanced disease. As the incidence of obesity
      associated malignancies, including esophageal adenocarcinoma (EAC) continues to
      increase and treatment with checkpoint inhibitors are being FDA approved for a
      broader range of cancers, it is important to assess how anti-PD-1 treatment might
      exacerbate pre-existing inflammatory processes at other sites. Outside the EAC
      tumor, the omentum and liver were found to be enriched with substantial
      populations of PD-1 expressing T cells. Treatment of omental and hepatic T cells
      with anti-PD-1 (clone EH12.2H7) did not enhance inflammatory cytokine expression
      or proliferation, but transiently increased CD107a expression by CD8+ T cells.
      Importantly, PD-1-expressing T cells are significantly lower in EAC tumor post
      neoadjuvant chemoradiotherapy, suggesting that combination with specific
      conventional treatments may severely impair the efficacy of anti-PD-1
      immunotherapy. This study provides evidence that systemically administered anti
      PD-1 treatment is unlikely to exacerbate pre-existing T cell-mediated
      inflammation outside the tumor in obesity-associated cancers, such as EAC.
      Furthermore, our data suggests that studies are required to identify the negative
      impact of concomitant therapies on PD-1 expression in order to boost overall
      response rates.

PMID- 29339210
TI  - The NLRP3 inflammasome: Role in metabolic disorders and regulation by metabolic
      pathways.
AB  - Inflammasomes are large multimolecular complexes present in the cytosol of
      stimulated immune cells; they mediate the activation of caspase-1, leading to
      cellular pyroptosis. So far, a variety of studies on inflammasomes have emerged,
      and the best-studied is the NLRP3 inflammasome that is involved in many
      inflammatory responses. Furthermore, its relationship with metabolism is gaining
      increasing attention in this field. In this review, we discuss the importance of
      the NLRP3 inflammasome in metabolic disorders and its close association with
      metabolic pathways.

PMID- 29339211
TI  - Long non-coding RNA XIST promotes TGF-beta-induced epithelial-mesenchymal
      transition by regulating miR-367/141-ZEB2 axis in non-small-cell lung cancer.
AB  - Growing evidence shows that lncRNA XIST functions as an oncogene accelerating
      tumor progression. Transforming growth factor beta (TGF-beta)-induced epithelial
      mesenchymal transition (EMT) plays a key role in tumor metastasis. However, it is
      still unclear whether lncRNA XIST is implicated in TGF-beta-induced EMT and
      influences cell invasion and metastasis in non-small-cell lung cancer (NSCLC).
      Here, we observed increased expression of lncRNA XIST and ZEB2 mRNA in metastatic
      NSCLC tissues. Knockdown of lncRNA XIST inhibited ZEB2 expression, and repressed
      TGF-beta-induced EMT and NSCLC cell migration and invasion. Being in consistent
      with the in vitro findings, the in vivo experiment of metastasis showed that
      knockdown of lncRNA XIST inhibited pulmonary metastasis of NSCLC cells in mice.
      In addition, knockdown of ZEB2 expression can inhibit TGF-beta-induced EMT and
      NSCLC cell migration and invasion. Mechanistically, lncRNA XIST and ZEB2 were
      targets of miR-367 and miR-141. Furthermore, both miR-367 and miR-141 expression
      can be upregulated by knockdown of lncRNA XIST. Taken together, our study reveals
      that lncRNA XIST can promote TGF-beta-induced EMT and cell invasion and
      metastasis by regulating miR-367/miR-141-ZEB2 axis in NSCLC.

PMID- 29339213
TI  - NRP-2 in tumor lymphangiogenesis and lymphatic metastasis.
AB  - Neuropilin-2 (NRP-2) not only functions as a receptor for semaphorins, a family
      of neural axon guidance factors, but also interacts with VEGFs, a family of
      vascular endothelial growth factors. As an independent receptor or a co-receptor,
      NRP-2 binds to ligands VEGF-C/D, activates the VEGF-C/D-NRP-2 signaling axis, and
      further regulates lymphangiogenesis-associated factors in both lymphatic
      endothelial cells (LECs) and some tumor cells during tumor progression. Via VEGF
      C/D-NRP-2 axis, NRP-2 induces LEC proliferation, reconstruction and
      lymphangiogenesis and subsequently promotes tumor cell migration, invasion and
      lymphatic metastasis. There are similarities and differences among NRP-1, NRP-2
      and VEGFR-3 in chemical structure, ligand specificity, chromosomal location,
      soluble protein forms, cellular functions and expression profiles. High
      expression of NRP-2 in LECs and tumor cells has been observed in different
      anatomic sites, histological patterns and progression stages of various tumors,
      especially during tumor lymphangiogenesis and lymphatic metastasis, and therefore
      the NRP-2 and VEGF-C/D-NRP-2 axis are closely related to tumor development,
      progression, invasion, and metastasis. In addition, it is important for prognosis
      of tumor. The studies on NRP-2 targeted therapy have recently achieved some
      successes, utilizing NRP-2 blocking antibodies, NRP-2 inhibitory peptides,
      soluble NRP-2 antagonists, small molecule inhibitors and various NRP-2 gene
      therapeutic strategies.

PMID- 29339212
TI  - Autophagy and T cell metabolism.
AB  - Autophagy, a highly conserved catabolic process that involves the degradation and
      recycling of intracellular components in the lysosome, has emerged as a key
      process in the maintenance of T cell homeostasis and the regulation of T cell
      differentiation and function. In this review, we provide an overview of the
      mechanisms that mediate the regulation of autophagy in T cells and discuss
      different cellular processes that are under the control of autophagy in CD4+ and
      CD8+ T cells. A special emphasis is placed on the role that autophagy plays in
      the modulation of T cell metabolism and the consequences of this regulation on
      functional states and programs of differentiation in specific T cell populations.

PMID- 29339214
TI  - Preparation and spectral properties of europium hydrogen squarate microcrystals.
AB  - A simple scheme for preparation of europium hydrogen squarate octahydrate
      microcrystals, Eu(HSq)3.8H2O is demonstrated. The microcrystalline powders
      obtained have a potential application as non-centrosymmetric and UV radiation -
      protective hybrid optical material. The site-symmetry of the Eu - ion is C2V or
      lower, obtained from diffuse reflectance spectra. The formation of europium
      hydrogen squarate is supported by IR - spectroscopy, UV-vis spectroscopy,
      chemical analysis and X-ray diffraction. A detailed analysis of the UV-vis and IR
      spectra of the micropowders prepared is presented.

PMID- 29339215
TI  - Registration in the international prospective register of systematic reviews
      (PROSPERO) of systematic review protocols was associated with increased review
      quality.
AB  - OBJECTIVES: A priori registration of systematic review protocols in international
      prospective register of systematic reviews (PROSPERO) can help reduce selective
      reporting of outcomes. The aim of this study was to assess the association
      between registration of orthodontic systematic reviews in PROSPERO and review
      quality with the Assessment of Multiple Systematic Reviews (AMSTAR) tool. STUDY
      DESIGN AND SETTING: Seven databases were searched for systematic reviews
      with/without meta-analysis in orthodontics published between 2012 and 2016. After
      duplicate study selection and data extraction, the quality of identified reviews
      was assessed in duplicate with the AMSTAR tool. Descriptive statistics of medians
      and interquartile ranges (IQRs) and chi-square/Fisher exact tests were
      calculated. Univariable/multivariable linear regression modeling was implemented
      to assess the effect of review registration on %AMSTAR score at alpha of 5%.
      RESULTS: A total of 182 orthodontic systematic reviews were identified, 37
      (20.3%) of which were registered. Considerable differences were seen in AMSTAR
      between registered (median = 86.4%; IQR = 77.3-95.5%) and nonregistered reviews
      (median = 72.7%; IQR = 59.1-81.8%). After adjustment, registration in PROSPERO
      was associated with an average increase in %AMSTAR score of 6.6% (95% confidence
      interval = 1.0-12.3%). CONCLUSION: Although only a small percentage of
      orthodontic systematic reviews was registered a priori in PROSPERO, registered
      reviews were of higher quality than nonregistered reviews.

PMID- 29339216
TI  - In vivo biotinylated calpastatin improves the affinity purification of human m
      calpain.
AB  - Recently we established a novel affinity purification method for calpain by
      exploiting the specific and reversible binding properties of its intrinsically
      disordered protein inhibitor, calpastatin. The immobilization strategy relied on
      the strength and specificity of the biotin - streptavidin interaction. Here, we
      report an improved and optimized method that even enables the general
      applicability of in vivo biotinylated (intrinsically disordered) proteins in any
      affinity capture strategy. Since in vitro chemical biotinylation is only
      accomplished with reagents that lack exact site specificity, it can not only
      cause sample heterogeneity but it can also hamper the functionality of the
      biotinylated molecules. Therefore, we have developed a recombinant expression
      protocol to produce in vivo biotinylated human calpastatin domain 1 (hCSD1) in
      Escherichia coli. We have experimentally verified that the biotinylated
      polypeptide tag is compatible with the intrinsically disordered state of hCSD1
      and that it does not influence the functional properties of this intrinsically
      disordered protein (IDP). The in vivo biotinylated hCSD1 was then used without
      the need of any prepurification step prior to the affinity capturing of its
      substrate, human m-calpain. This leads to a simplified purification strategy that
      allows capturing the calpain efficiently from a complex biological mixture with
      only a single chromatogaphic step and in a considerably reduced timeframe. Our
      approach is generally applicable through the in vivo biotinylation of any IDP of
      interest, and its practical implementation will showcase the power to exploit the
      properties of IDPs in affinity capture strategies.

PMID- 29339217
TI  - Effects of rutin on the physicochemical properties of skin fibroblasts membrane
      disruption following UV radiation.
AB  - Human skin provides the body's first line of defense against physical and
      environmental assaults. This study sought to determine how rutin affects the
      membrane electrical properties, sialic acid content, and lipid peroxidation
      levels of fibroblast membranes after disruption by ultraviolet (UV) radiation.
      Changes in cell function may affect the basal electrical surface properties of
      cell membranes, and changes can be detected by electrokinetic measurements. The
      charge density of the fibroblast membrane surface was measured as a function of
      pH. A four-component equilibrium model was used to describe the interaction
      between ions in solution and ions on the membrane surface. Agreement was found
      between experimental and theoretical charge variation curves of fibroblast cells
      between pH 2.5 and 8. Sialic acid content was determined by Svennerholm's
      resorcinol method, and lipid peroxidation was estimated by measuring the
      malondialdehyde level. Compared to untreated cells, ultraviolet A (UVA)- or
      ultraviolet B (UVB)-treated skin cell membranes exhibited higher concentrations
      of acidic functional groups and higher average association constants with
      hydroxyl ions, but lower average association constants with hydrogen ions.
      Moreover, our results showed that UVA and UVB radiation is associated with
      increased levels of sialic acid and lipid peroxidation products in fibroblasts.
      Rutin protected cells from some deleterious UV-associated membrane changes,
      including changes in electrical properties, oxidative state, and biological
      functions.

PMID- 29339218
TI  - Prophylactic efficacy of patchoulene epoxide against ethanol-induced gastric
      ulcer in rats: Influence on oxidative stress, inflammation and apoptosis.
AB  - Patchoulene epoxide (PAO), a tricyclic sesquiterpene isolated from the long
      stored patchouli oil, has been demonstrated the anti-inflammatory activity in
      vivo based on our previous study. However, the gastric protective effect of PAO
      still remains unknown. Therefore, in the present study, ethanol-induced gastric
      ulcer model was carried out to evaluate the anti-ulcerogenic activity of PAO and
      to elucidate the potential mechanisms that involves. According to our results,
      macroscopic examination revealed that PAO could significantly reduce ethanol
      induced gastric ulcer areas as compared with the vehicle group, which was also
      supported by the histological evaluation result. As for its potential mechanism,
      the anti-inflammatory activity of PAO contributed to gastric protection through
      reversing the imbalance between pro- and anti-inflammatory cytokines and
      modulating the expressions of NF-kappaB pathway-related proteins including p
      IkappaBalpha, IkappaBalpha, p-p65 and p65. Besides, PAO was able to enhance the
      expressions of antioxidant enzymes including glutathione (GSH), superoxide
      dismutase (SOD) and catalase (CAT), and down-regulate malonaldehyde (MDA), an
      indicator of lipid peroxidation. Furthermore, immunohistochemistry analysis
      exhibited potent anti-apoptosis effect of PAO, as evidence by down-regulating the
      protein expression of caspase-3, Fas and Fasl. Additionally, we also demonstrated
      that PAO could replenish PGE2 and NO mucosal defense. In conclusion, these
      findings suggested that PAO has gastric protective activity against ethanol and
      this might be related to its influence on inflammatory response, oxidative
      stress, apoptosis cascade and gastric mucosal defense.

PMID- 29339219
TI  - Caffeine-supplemented diet modulates oxidative stress markers and improves
      locomotor behavior in the lobster cockroach Nauphoeta cinerea.
AB  - The effects of caffeine supplementation is well documented in conventional animal
      models, however, in the lobster cockroaches Nauphoeta cinerea, they have not been
      reported. Thus, the aim of this study was to investigate the locomotor behavior
      and biochemical endpoints in the head of the nymphs of N. cinerea following 60
      days exposure to food supplemented with 0, 0.5, 1.0, 2.5, 5.0 and 10.0 mg of
      caffeine/g of diet. The analysis of the locomotor behavior using the video
      tracking software, Any-maze, for 12 min revealed that caffeine supplementation
      caused significant behavioral improvement. There was increase in distance
      travelled, velocity, frequency of rotation and turn angle (stereotypical behavior
      such as circling movements), and this was supported by the representative track
      plots of the path travelled by cockroaches in the open-field arena. In addition,
      caffeine supplementation markedly increased total thiol and non-protein thiol
      glutathione (GSH) levels in the heads of cockroaches, and this was in parallel
      with significant reduction of lipid peroxidation and free Fe(II) content. Taking
      together, our results indicate that long-term caffeine supplementation may exert
      preventive effects against oxidative stress and support the use of N. cinerea as
      an efficient alternative model to assess the efficacy of food molecules.

PMID- 29339220
TI  - A new chimeric triple reporter fusion protein as a tool for in vitro and in vivo
      multimodal imaging to monitor the development of African trypanosomes and
      Leishmania parasites.
AB  - Trypanosomiases and leishmaniases, caused by a group of related protist
      parasites, are Neglected Tropical Diseases currently threatening >500 million
      people worldwide. Reporter proteins have revolutionised the research on
      infectious diseases and have opened up new advances in the understanding of
      trypanosomatid-borne diseases in terms of both biology, pathogenesis and drug
      development. Here, we describe the generation and some applications of a new
      chimeric triple reporter fusion protein combining the red-shifted firefly
      luciferase PpyREH9 and the tdTomato red fluorescent protein, fused by the TY1
      tag. Expressed in both Trypanosoma brucei brucei and Leishmania major transgenic
      parasites, this construct was successfully assessed on different state-of-the-art
      imaging technologies, at different scales ranging from whole organism to cellular
      level, both in vitro and in vivo in murine models. For T. b. brucei, the
      usefulness of this triple marker to monitor the entire parasite cycle in both
      tsetse flies and mice was further demonstrated. This stable reporter allows to
      qualitatively and quantitatively scrutinize in real-time several crucial aspects
      of the parasite's development, including the development of African trypanosomes
      in the dermis of the mammalian host. We briefly discuss developments in bio
      imaging technologies and highlight how we could improve our understanding of
      parasitism by combining the genetic engineering of parasites to the one of the
      hosting organisms in which they complete their developmental program.

PMID- 29339221
TI  - The Founding Fathers vs Jerome Cochran: Organization and Development of the
      Southern Surgical and Gynecological Association in Birmingham.

PMID- 29339222
TI  - Measurement variability of liver metastases from neuroendocrine tumors on
      different magnetic resonance imaging sequences.
AB  - PURPOSE: To assess dimension measurement variability of liver metastases from
      neuroendocrine tumors (LMNET) on different magnetic resonance imaging (MRI)
      sequences. MATERIAL AND METHODS: In this institutional review board-approved
      retrospective study from January 2011 to December 2012, all liver MRI
      examinations performed at our department in patients with at least one measurable
      LMNET according to response evaluation criteria in solid tumors (RECIST1.1) were
      included. Up to two lesions were selected on T2-weighted MR images. Three
      reviewers independently measured long axes of 135 hepatic metastases in 30
      patients (16 men, 14 women, mean age 61+/-11.4 (SD) years; range 28-78 years),
      during two separate reading sessions, on T2-weighted, diffusion-weighted MRI
      (DWI) (b; 50, 400, 800 s/mm2) and arterial, portal and late phases after
      intravenous administration of a gadolinium chelate. Intraclass-correlation
      coefficients and Bland-Altman plots were used to assess intra-and interobserver
      variability. RESULTS: Intra- and interobserver agreements ranged between 0.87
      0.98, and 0.88-0.97, respectively. Intersequence agreements ranged between 0.92
      [95%CI: 0.82-0.98] and 0.98 [95%CI: 0.93-0.99]. 95% limits of agreement for
      measurements were -10.2%,+8.9% for DWI (b=50s/mm2) versus -21.9%,+24.2% and 
      15.8,+17.2% for arterial and portal phases, respectively. CONCLUSION: An
      increase<9% in measurement and a decrease of -10% on DWI should not be considered
      as true changes, with 95% confidence, versus 24% and -22% on arterial and 17%, 
      16% on portal phases, respectively. DWI might thus be the most reliable MR
      sequence for monitoring size variations of LMNETs.

PMID- 29339223
TI  - Leishmania infections in Austrian soldiers returning from military missions
      abroad: a cross-sectional study.
AB  - OBJECTIVES: The incidence of leishmaniasis is known to increase in conflict
      areas. The aims of this study were to determine the exposure to Leishmania
      species in Austrian soldiers returning from missions abroad and to assess
      possible risk factors. METHODS: A retrospective explorative cross-sectional
      serologic study was conducted in 225 healthy Austrian soldiers returning from UN
      or EU peacekeeping missions in Syria, Lebanon and Bosnia and Herzegovina (BIH).
      Sera were tested for anti-Leishmania antibodies using a commercial enzyme-linked
      immunosorbent assay. All positive individuals were screened for Leishmania DNA by
      PCR targeting the ITS1 region using EDTA blood samples. RESULTS: In total, 13.3%
      (30/225) of the individuals tested were either positive (8%, 18/225) or
      borderline (5.3%, 12/225) in the enzyme-linked immunosorbent assay, with the
      highest seroprevalence in soldiers returning from Syria (17.8%, 18/101; 12
      positive, six borderline), second from Lebanon (11.1%, 7/63; four positive, three
      borderline) and lowest from BIH (8.2%, 5/61; two positive, three borderline). Ten
      soldiers returning from Syria and one from BIH were also positive for Leishmania
      DNA. Six of these were identified as Leishmania donovani/infantum complex, two as
      L. tropica and another three as mixed infections by DNA sequencing. Epidemiologic
      data were collected via a questionnaire, and seropositivity was correlated with a
      history of insect bites that took a long time to heal (odds ratio, 5.33; 95%
      confidence interval, 1.23-23.04; p 0.025). CONCLUSIONS: Although pretravel
      serologic data were not available in this study, the exposure of soldiers to
      Leishmania spp. during their missions can be assumed to be considerable. Because
      even asymptomatic infections may resurge in case of emerging immunodeficiencies,
      adequate prevention measures seem important.

PMID- 29339224
TI  - Emerging souvenirs-clinical presentation of the returning traveller with imported
      arbovirus infections in Europe.
AB  - BACKGROUND: Arboviruses are an emerging group of viruses that are causing
      increasing health concerns globally, including in Europe. Clinical presentation
      usually consists of a nonspecific febrile illness that may be accompanied by
      rash, arthralgia and arthritis, with or without neurological or haemorrhagic
      syndromes. The range of differential diagnoses of other infectious and
      noninfectious aetiologies is broad, presenting a challenge for physicians. While
      knowledge of the geographical distribution of pathogens and the current
      epidemiological situation, incubation periods, exposure risk factors and
      vaccination history can help guide the diagnostic approach, the nonspecific and
      variable clinical presentation can delay final diagnosis. AIMS AND SOURCES: This
      narrative review aims to summarize the main clinical and laboratory-based
      findings of the three most common imported arboviruses in Europe. Evidence is
      extracted from published literature and clinical expertise of European arbovirus
      experts. CONTENT: We present three cases that highlight similarities and
      differences between some of the most common travel-related arboviruses imported
      to Europe. These include a patient with chikungunya virus infection presenting in
      Greece, a case of dengue fever in Turkey and a travel-related case of Zika virus
      infection in Romania. IMPLICATIONS: Early diagnosis of travel-imported cases is
      important to reduce the risk of localized outbreaks of tropical arboviruses such
      as dengue and chikungunya and the risk of local transmission from body fluids or
      vertical transmission. Given the global relevance of arboviruses and the
      continuous risk of (re)emerging arbovirus events, clinicians should be aware of
      the clinical syndromes of arbovirus fevers and the potential pitfalls in
      diagnosis.

PMID- 29339225
TI  - Metabolism and pharmacokinetics of a potent N-acylindole antagonist of the OXE
      receptor for the eosinophil chemoattractant 5-oxo-6,8,11,14-eicosatetraenoic acid
      (5-oxo-ETE) in rats and monkeys.
AB  - We previously identified the indole 264 as a potent in vitro antagonist of the
      human OXE receptor that mediates the actions of the powerful eosinophil
      chemoattractant 5-oxo-ETE. No antagonists of this receptor are currently
      commercially available or are being tested in clinical studies. The lack of a
      rodent ortholog of the OXE receptor has hampered progress in this area because of
      the unavailability of commonly used mouse or rat animal models. In the present
      study, we examined the feasibility of using the cynomolgus monkey as an animal
      model to investigate the efficacy of orally administered 264 in future in vivo
      studies. We first confirmed that 264 is active in monkeys by showing that it is a
      potent inhibitor of 5-oxo-ETE-induced actin polymerization and chemotaxis in
      granulocytes. The major microsomal metabolites of 264 were identified by
      cochromatography with authentic chemically synthesized standards and LC-MS/MS as
      its omega2-hydroxy and omega2-oxo derivatives, formed by omega2-oxidation of its
      hexyl side chain. Small amounts of omega1-oxidation products were also
      identified. None of these metabolites have substantial antagonist potency. High
      levels of 264 appeared rapidly in the blood following oral administration to both
      rats and monkeys, and declined to low levels by 24 h. As with microsomes, its
      major plasma metabolites in monkeys were omega2-oxidation products. We conclude
      that the monkey is a suitable animal model to investigate potential therapeutic
      effects of 264. This, or a related compound with diminished susceptibility to
      omega2-oxidation, could be a useful therapeutic agent in eosinophilic disorders
      such as asthma.

PMID- 29339226
TI  - Model and methods to assess hepatic function from indocyanine green fluorescence
      dynamical measurements of liver tissue.
AB  - The indocyanine green (ICG) clearance, presented as plasma disappearance rate is,
      presently, a reliable method to estimate the hepatic "function". However, this
      technique is not instantaneously available and thus cannot been used intra
      operatively (during liver surgery). Near-infrared spectroscopy enables to assess
      hepatic ICG concentration over time in the liver tissue. This article proposes to
      extract more information from the liver intensity dynamics by interpreting it
      through a dedicated pharmacokinetics model. In order to account for the different
      exchanges between the liver tissues, the proposed model includes three
      compartments for the liver model (sinusoids, hepatocytes and bile canaliculi).
      The model output dependency to parameters is studied with sensitivity analysis
      and solving an inverse problem on synthetic data. The estimation of model
      parameters is then performed with in-vivo measurements in rabbits (El-Desoky et
      al. 1999). Parameters for different liver states are estimated, and their link
      with liver function is investigated. A non-linear (Michaelis-Menten type)
      excretion rate from the hepatocytes to the bile canaliculi was necessary to
      reproduce the measurements for different liver conditions. In case of bile duct
      ligation, the model suggests that this rate is reduced, and that the ICG is
      stored in the hepatocytes. Moreover, the level of ICG remains high in the blood
      following the ligation of the bile duct. The percentage of retention of
      indocyanine green in blood, which is a common test for hepatic function
      estimation, is also investigated with the model. The impact of bile duct ligation
      and reduced liver inflow on the percentage of ICG retention in blood is studied.
      The estimation of the pharmacokinetics model parameters may lead to an evaluation
      of different liver functions.

PMID- 29339227
TI  - A novel biphenolic ligand for selective Mg2+ and Zn2+ ions sensing followed by
      colorimetric, spectroscopic and cell imaging methods.
AB  - The (E)-2-((2-hydrohy-5-methylphenylimino) methyl) phenol ligand was synthesized.
      The receptor was characterized by IR, 1H and 13C NMR and CHN analysis. The ligand
      exhibits colorimetric and fluorometric sensing of Zn2+ and Mg2+ ions in semi
      aqueous medium (DMSO-H2O). The receptor was tested with series of transition
      metal ions (Cr2+, Fe2+, Ni2+, Co2+, Cu2+, Zn2+) and heavy metal ions (Sn2+, Pd2+,
      Ce2+, Hg2+, Cd2+) and the essential human body elements like Ca2+, Mg2+, Na+ and
      K+ ions. The naked eye colorimetric sensing was absorbed only for Zn2+ and Mg2+.
      Both ions (ZnCl2 and MgCl2 in H2O), when added to the colorless solutions of the
      receptor of about 1 equivalence in incremental additions turn the solution into
      bright turmeric yellow. All other ions remain inactive, in colorimetric sensing.
      Further the Zn2+ and Mg2+ ions were probed by absorption and emission
      spectroscopy through incremental addition of respective metal ions. The in-situ
      deprotonation of the ligand on both Mg2+ and Zn2+ ions binding was confirmed by
      1H NMR titration studies. The imino nitrogen of the receptor is not coordinated
      to the metal ions. The Job's plot studies reveal the 1:2 binding ratio of metal
      ions to the receptor. The high fold fluorescence output on metal ions binding was
      positively used to sense the Zn2+ and Mg2+ ions, separately and together in HeLa
      cancer cells through cell imaging.

PMID- 29339228
TI  - Stability and plasmatic protein binding of novel zidovudine prodrugs: Targeting
      site ii of human serum albumin.
AB  - Despite its vastly demonstrated clinical efficacy, zidovudine (AZT) exhibits
      several suboptimal pharmacokinetic properties. In particular, its short plasmatic
      half-life (t1/2 ~ 1 h) is related to its low bound fraction to whole plasmatic
      proteins and in particular to human serum albumin (HSA). The design of prodrugs
      constitutes a promising strategy to enhance AZT pharmacokinetic properties,
      including its affinity for HSA. Recently, we reported the synthesis and chemical
      stability evaluation of three novel prodrugs of AZT obtained by derivatization
      with dicarboxylic acids (1-3). In this work, we present the design, synthesis and
      evaluation of chemical and enzymatic stabilities of a novel series of double
      prodrugs of AZT obtained by derivatization of 1-3 with a methylated l
      phenylalanine moiety (4-6). In addition, the plasmatic protein binding properties
      were studied both by experimental and theoretical techniques. Prodrugs 4-6 were
      found to be relatively stable at pH 7.4 (t1/2 between 4.1 and 57.8 h), while also
      demonstrated adequate stabilities in human plasma at 37  degrees C (t1/2 between
      1.0 and 2.1 h). Also, prodrugs 4-6 were able to regenerate AZT at a rate that
      depended on the length of the alkyl chain in 1-3. Additionally, 4-6 exhibited a
      significantly increased binding to plasmatic proteins (between 52.1 and 72.5%)
      with respect to AZT (12%) and 1-3 (between 26 and 34%). It is noteworthy that the
      displacement experiments with HSA site I and II markers, demonstrated that 4-6
      bound to a different site than that of AZT and 1-3. Molecular modeling studies
      (i.e. molecular docking and free energy of binding analysis) were applied to shed
      light at an atomistic level on the pharmacodynamic properties driving the
      interaction of 4-6 with HSA. Overall, the present work provides a state of the
      art contribution to the design and development of novel prodrugs of AZT with
      optimized pharmacokinetic properties.

PMID- 29339229
TI  - A rare case of Candida glabrata spondylodiscitis: case report and literature
      review.
AB  - BACKGROUND: Spondylodiscitis is an infection of the vertebral column, the
      incidence of which is increasing due to an increase in the susceptible population
      and improved ascertainment. This disease has been associated with a wide range of
      microorganisms. Fungal spondylodiscitis is uncommon (0.5-1.6%) and strongly
      associated with immunosuppression and diabetes (Gouliouris et al., 2010). A rare
      case of Candida glabrata spondylodiscitis in a non-neutropenic diabetic patient
      is reported herein, along with a review of the literature. CASE REPORT: A case of
      C. glabrata spondylodiscitis of L3-L4 metameres was diagnosed. The diagnosis was
      obtained through open biopsy of an abscess and culture examination. The patient
      was treated with anidulafungin and surgical debridement of the lesion.
      CONCLUSIONS: The diagnosis of spondylodiscitis is often delayed or missed.
      Physicians should consider this entity in the differential diagnosis of lumbar
      pain in order to initiate an appropriate therapy to prevent spinal cord lesions
      and disability. This is particularly relevant in the case of a fungal aetiology,
      as there is a recognized global shift towards invasive candidiasis due to non
      albicans Candida species, in particular C. glabrata, which has variable
      susceptibility to antifungal drugs.

PMID- 29339230
TI  - Balanced crystalloids vs 0.9% saline for adult patients undergoing non-renal
      surgery: A meta-analysis.
AB  - BACKGROUND: Fluid maintenance and resuscitation is an important strategy during
      major surgeries. There has been a debate on the choice of crystalloids over the
      past decades. 0.9% saline (normal saline) is more likely to cause hyperchloremic
      acidosis when compared to balanced crystalloids with low chloride content. Meta
      analyses comparing these two kinds of crystalloids have been performed in renal
      transplantations. We aim to compare the safety of balanced crystalloids to normal
      saline among adult patients undergoing non-renal surgery. METHODS: Relevant
      articles were searched through PubMed, Embase and the Cochrane Library. Nine
      randomized controlled trials (including 871 participants) comparing balanced
      crystalloids to normal saline on adult patients undergoing non-renal surgery were
      finally included. Possible effects were calculated using meta-analysis. RESULTS:
      Patients in the normal saline group had significantly lower postoperative pH (MD:
      0.05; 95% CI: 0.04-0.06; p < .001; I2 = 82%) and base excess (MD: 2.04; 95% CI:
      1.44-2.65; p < .001; I2 = 87%). The postoperative serum chloride level was
      significantly higher in the normal saline group (MD: -4.79; 95% CI: -8.13~-1.45;
      p = .005; I2 = 95%). CONCLUSION: Comparing to normal saline, balanced
      crystalloids are more beneficial in keeping postoperative electrolytes and acid
      base balance among adult patients undergoing non-renal surgery. Future researches
      should pay more attention to meaningful clinical outcomes concerning the safety
      of balanced crystalloids and normal saline.

PMID- 29339231
TI  - Respiratory patterns in field collected brown locust, Locustana pardalina, in the
      gregarious phase.
AB  - In this paper we report on the metabolic rates and respiratory patterns measured
      from gregarious brown locusts, Locustana pardalina, collected from the Nama Karoo
      region in South Africa. All five instar hopper stages and adults were collected
      over a three year period when significant numbers of locust swarms were seen.
      Flow-through respirometry was used to measure the CO2 emission from individual
      locusts from all the developmental stages and adults within a week of collection.
      Carbon dioxide emission scaled hypometrically with mass, 0.863 +/- 0.026. Except
      in the 1st and 5th instar stage there was no difference in the mass specific rate
      of CO2 emission (V<ce:small-caps>CO2</ce:small-caps>). These had significantly
      higher metabolic rates compared to the other stages which reflects their biology,
      with the 1st instar undergoing rapid growth and the 5th instar also undergoing
      rapid growth and development in preparation for becoming an adult. The 1st
      instars used a form of continuous gas exchange while all the other stages showed
      discontinuous gas exchange cycles. A clear burst phase and interburst periods
      could be seen. The 2nd and 3rd instars use mainly diffusion to expel CO2 and so
      exhibited an open form of the burst phase. There was an increase in CO2 volleys
      seen in the burst phase from the 4th instar stage onwards thus indicating an
      increased use of convection. There was no change in the duration or frequency of
      the discontinuous gas exchange cycles through the locust development or with body
      mass.

PMID- 29339232
TI  - Diapause in Drosophila melanogaster - Photoperiodicity, cold tolerance and
      metabolites.
AB  - Unlike many insects where photoperiod per se induces diapause, reproductive
      arrest in Drosophila melanogaster adult females is observed at colder
      temperatures and can be enhanced by shorter photoperiods. Traditional
      experimental protocols raise flies at 25  degrees C from the larval stage and
      then the adults are placed at 12  degrees C for between 12 and 28 days. After 12
      days diapause levels are usually higher than at 28 days, suggesting that the
      flies are in a cold induced quiescence, rather than a true diapause. By raising
      flies at more realistic lower temperatures, we observe quite dramatic and counter
      intuitive effects on diapause, whose levels nevertheless correlate with various
      indices of cryoprotectant metabolites as well as resistance to chill shock. We
      also observe that photoperiodic effects are minimised when very small temperature
      oscillations associated with the light-dark incubator cycles are neutralised. Our
      results suggest that the reported photoperiodic component of fly diapause, at
      least in these strains, is mostly due to thermoperiodic rather than photoperiodic
      stimuli. In addition, the metabolite and chill shock analyses reveal that even by
      12 days, flies are entering a state that is resistant to environmental stresses.

PMID- 29339233
TI  - FTIR as an easy and fast analytical approach to follow up microbial growth during
      fungal pretreatment of poplar wood with Phanerochaete chrysosporium.
AB  - Since the determination of the fermentation kinetics is one of the main
      challenges in solid state fermentation, the quantitative measurement of biomass
      growth during microbial pretreatment by FTIR spectroscopy in Attenuated Total
      Reflectance mode was evaluated. Peaks at wave numbers of 1651 cm-1 and 1593 cm-1
      showed to be affected during pretreatment of poplar wood particles by
      Phanerochaete chrysosporium MUCL 19343. Samples with different microbial biomass
      fractions were obtained from two different experiments, i.e., shake flask and
      fixed-bed reactor experiments. The glucosamine concentration was compared to the
      normalized absorbance ratio of the 1651 cm-1 to 1593 cm-1 peak, measured by FTIR
      ATR, and resulted in a linear relationship. The application of a normalized
      absorbance ratio in function of time provided a graph that was similar to the
      microbial growth curve. Application of FTIR in ATR mode to follow-up kinetics
      during solid state fermentation seems to be a fast and easy alternative to
      laborious measurement techniques, such as glucosamine determination.

PMID- 29339234
TI  - Stoichiometric variation and loading capacity of a high-loading anammox attached
      film expanded bed (AAEEB) reactor.
AB  - The nitrogen loading rate (NLR) of an anammox attached film expanded bed (AAFEB)
      reactor was increased from 5.0 to 60.0 gN/L/d. During the stable operational
      period, the TN removal efficiency maintained at 87.3 +/- 2.5%, and a maximum
      nitrogen removal rate (NRR) of 44.9 +/- 0.3 gN/L/d was achieved. Overload
      resulted in the sharp deterioration of reactor performance, the ratio of
      (Food/Microorganism)/SAA should be maintained at lower than 66 +/- 7% to ensure
      the stable operation of the AAFEB reactor. New stoichiometric equations for the
      anammox process under the low NLR condition (5.0 gN/L/d) and the high NLR
      condition (50.0 gN/L/d) were proposed. The quantitative SAA-cytochrome heme C
      relationship was established for the first time that providing a simple way for
      monitoring the reactor performance. Substrate tolerance ability was significantly
      increased that proving the stability of the AAFEB reactor was continuously
      enhanced during the stable operational periods.

PMID- 29339235
TI  - A highly efficient two-stage cultivation strategy for lutein production using
      heterotrophic culture of Chlorella sorokiniana MB-1-M12.
AB  - A heterotrophic mutant of Chlorella sorokiniana MB-1-M12 was evaluated for its
      ability to produce lutein using organic carbon and nitrogen sources and without
      light irradiation. In batch fermentation, the maximal lutein content (3.67 mg
      lutein/g biomass) and productivity (2.84 mg/L/d) could be obtained when
      cultivated in BG-11 medium with 7.5 g/L glucose, 0.75 g/L urea, pH 7.5 and a C/N
      ratio of 10. A novel two-stage cultivation strategy that integrates fed-batch and
      semi-batch operations was applied to enhance the lutein production performance.
      When growing MB-1-M12 strain in a 5L fermenter using the optimal operation
      strategies, the maximum biomass concentration, biomass productivity, lutein
      content and lutein productivity could reach 25 g/L, 4.88 mg/L/d, 5.88 mg/g and
      16.2 mg/L/d, respectively. This high lutein productivity could significantly
      reduce the cultivation time and the associated costs, indicating the potential of
      using MB-1-M12 strain for heterotrophic lutein production in commercial scale.

PMID- 29339236
TI  - In-depth study of rice husk torrefaction: Characterization of solid, liquid and
      gaseous products, oxygen migration and energy yield.
AB  - Torrefaction is a promising method for biomass upgrading, and analysis of all
      products is the essential way to reveal torrefaction mechanism. In this study,
      torrefaction of rice husk was performed at 210-300  degrees C. Results showed
      that the fuel properties of solid products were greatly enhanced upon removal of
      oxygen. The gaseous products were mainly CO2 (52.9-73.8 vol%), followed by CO
      (26.3-39.2 vol%). The liquid product was mainly water and some tar, and the
      latter contained acids, furans, ketones, aldehydes, and phenols, among which the
      relative content of acids was the highest. Torrefaction temperature has obvious
      effects on the oxygen migration. Within the temperature range of 210-300  degrees
      C, 9.5-63.2% of oxygen in rice husk was migrated to the gaseous and liquid
      products. The H2O was the major contributor to deoxygenation, followed by CO2 and
      CO. Thus, formation of H2O, CO2, and CO during torrefaction is important as it
      achieves the purpose of intense deoxygenation.

PMID- 29339238
TI  - Topical betaxolol for treating relapsing paronychia with pyogenic granuloma-like
      lesions induced by epidermal growth factor receptor inhibitors.

PMID- 29339237
TI  - Assessing the outcomes, risks, and costs of local versus general anesthesia: A
      review with implications for cutaneous surgery.
AB  - BACKGROUND: There is a paucity of data providing direct comparison of outcomes,
      complications, and costs between general and local anesthesia in cutaneous
      surgery. OBJECTIVE: Analyze the literature from dermatologic and other
      specialties to compare outcomes, risks, and costs of general and local
      anesthesia. METHODS: A retrospective analysis of case comparison studies from
      other specialties comparing outcomes, risks, and/or costs in local versus general
      anesthesia was performed. A review of the literature from dermatology and other
      specialties was included. RESULTS: A total of 51 studies were selected; 41 of
      them directly examined outcomes in procedures performed under local and general
      anesthesia, and none found a significant difference in outcomes. A total of 41
      studies measured adverse effects. Of these, 15 studies (36.6%) report
      significantly better outcomes between the 2 techniques. Only 2 studies (4.9%)
      report significantly improved outcomes with use of general anesthesia; 15 of 36
      studies (41.7%) report fewer adverse events in local anesthesia. Of the 13
      studies that examined costs, all (100%) found significantly decreased costs with
      use of local anesthesia. LIMITATIONS: These data cannot be seamlessly applied to
      all cases of cutaneous surgery. CONCLUSION: Local anesthesia techniques provide
      outcomes equal to or better than general anesthesia and with significantly lower
      costs.

PMID- 29339239
TI  - Multiple melanonychia striata as a sign of connective tissue disorders.

PMID- 29339240
TI  - Prevalence of type 2 diabetes mellitus among patients with hidradenitis
      suppurativa in the United States.
AB  - BACKGROUND: Few studies have evaluated the relationship between hidradenitis
      suppurativa (HS) and type 2 diabetes mellitus (T2DM), and the existing data show
      conflicting results. OBJECTIVE: To determine the prevalence of T2DM among
      patients with HS and identify at-risk demographic subgroups. METHODS: Cross
      sectional analysis identifying T2DM among patients with and without HS from a
      demographically heterogeneous population-based sample of more than 50 million
      patients in the United States. RESULTS: The overall prevalence of T2DM among
      patients with HS was 24.8% (10,705 of 43,105) compared with 15.6% (1,993,320 of
      12,527,570) among patients without HS. The prevalence was highest among patients
      with HS who were male (3045 of 10,785 [28.2%]), older (1945 of 3950 [49.2%]),
      nonwhite (4665 of 17,495 [26.7%]), obese (9065 of 30,855 [29.4%]), tobacco
      smokers (6880 of 25,005 [27.5%]), hypertensive (8595 of 19,610 [43.8%]), and
      hyperlipidemic (7965 of 17,190 [46.3%]). In univariable and multivariable
      analyses, patients with HS had 1.75 (95% confidence interval [CI], 1.71-1.79) and
      1.58 (95% CI, 1.54-1.62) times the odds, respectively, of having T2DM. HS was
      associated with T2DM across all demographic subgroups. The association was
      stronger for younger patients (an OR of 1.67 and 95% CI of 1.60-1.72 for ages 18
      44 years vs an OR of 1.50 and 95% CI of 1.41-1.61 for ages >=65 years).
      LIMITATIONS: We lacked information on HS disease severity. CONCLUSION: Patients
      with HS with risk factors, signs, or symptoms of T2DM should be screened.

PMID- 29339241
TI  - Role of graft-versus-host disease in the development of secondary skin cancers in
      hematopoietic stem cell transplant recipients: A meta-analysis.

PMID- 29339242
TI  - Combined acitretin and Candida antigen versus either agent alone in the treatment
      of recalcitrant warts.

PMID- 29339243
TI  - Black dots in palmoplantar warts-challenging a concept: A histopathologic study.

PMID- 29339244
TI  - Epigenetics of breast cancer: Biology and clinical implication in the era of
      precision medicine.
AB  - In the last years, mortality from breast cancer has declined in western countries
      as a consequence of a more widespread screening resulting in earlier detection,
      as well as an improved molecular classification and advances in adjuvant
      treatment. Nevertheless, approximately one third of breast cancer patients will
      develop distant metastases and eventually die for the disease. There is now a
      compelling body of evidence suggesting that epigenetic modifications comprising
      DNA methylation and chromatin remodeling play a pivotal role since the early
      stages of breast cancerogenesis. In addition, recently, increasing emphasis is
      being placed on the property of ncRNAs to finely control gene expression at
      multiple levels by interacting with a wide array of molecules such that they
      might be designated as epigenetic modifiers. In this review, we summarize the
      current knowledge about the involvement of epigenetic modifications in breast
      cancer, and provide an overview of the significant association of epigenetic
      traits with the breast cancer clinicopathological features, emphasizing the
      potentiality of epigenetic marks to become biomarkers in the context of precision
      medicine.

PMID- 29339245
TI  - Systematic review and evaluation of aspartame carcinogenicity bioassays using
      quality criteria.
AB  - The current review assessed cancer studies of aspartame based on a quality
      appraisal using the Klimisch grading system. Nine studies having complete
      histopathology were included: three 2-year studies by Searle; three transgenic
      mice studies by the NTP; three lifetime studies by the Ramazzini Institute. A
      tenth study limited to brain tumors was not rated. None were determined as
      Klimisch Code 1 (reliable without restrictions). The Searle studies predated GLP
      standards but their methodology was comparable; transgenic mouse models are not
      validated, but are accepted as supporting data. These studies were rated Klimisch
      Code 2 (reliable with restrictions). The Ramazzini Institute used a lifetime
      model of their own design that has been questioned due to high rates of
      spontaneous tumors, issues with tumor type diagnosis and concerns about the
      impact of chronic infections. As many of these problems could be attributed to
      using animals that died or were terminated near end of life, along with the other
      problems noted, these studies were rated Klimisch Code 3 (not reliable). As the
      Klimisch Code 2 studies demonstrated a lack of carcinogenic potential, and as
      aspartame is hydrolyzed to common components and lacks genotoxic activity, a
      conclusion that aspartame is not carcinogenic is supported.

PMID- 29339246
TI  - Absence of toxicity in Swiss mice following treatment with 7-acetoxy-4-aryl-3,4
      dihydrocoumarin: Acute and repeated-dose toxicity study.
AB  - Neoflavonoids, which are classified as 4-arylcoumarin (neoflavone), 3,4-dihydro-4
      arylcoumarin and neoflavene, have been the subject of a number of studies with
      respect to their therapeutic potential and, despite promising in vitro, ex vivo
      and in vivo pharmacological activities, there is a lack of studies demonstrating
      their toxicological properties. Therefore, this study aims to evaluate the acute
      (14 days) and repeated-dose (28 days) toxicity of synthetic neoflavonoid 7
      acetoxy-4-aryl-3,4-dihydrocoumarin in Swiss mice through parameters related to
      changes in body weight, food and water intake, hematological and biochemical
      parameters. Toxicity studies using acute doses (300 and 2000 mg/kg) and repeated
      doses (250, 500 and 1000 mg/kg) orally were carried out as per Organization for
      Economic Co-operation and Development (OECD) guidelines 423 and 407,
      respectively. Based on the results of this study, treatment with 7-acetoxy-4-aryl
      3,4-dihydrocoumarin was found to not cause clinical adverse symptoms and
      mortality in any animal used in the acute and repeated-dose toxicity study. In
      addition, no significant changes were observed in body weight and internal
      organs, food and water intake, hematological and biochemical parameters, compared
      to control group. Therefore, these results provide an initial understanding
      regarding the toxicity profile of 7-acetoxy-4-aryl-3,4-dihydrocoumarin, which can
      be considered a neoflavonoid with toxicity seen at doses higher than 2000 mg/kg
      in Swiss mice.

PMID- 29339247
TI  - Self-emulsifying peptide drug delivery systems: How to make them highly mucus
      permeating.
AB  - AIM: It was the aim of this study to evaluate the mucus permeating properties of
      self-emulsifying drug delivery systems (SEDDS) exhibiting different size and zeta
      potential. METHODS: Various SEDDS were prepared and characterized regarding
      droplet size, zeta potential and stability. Desmopressin was incorporated as
      model peptide drug and log P (SEDDS/water) was determined. Thereafter, mucus
      permeation studies with freshly isolated porcine mucus via Transwell method were
      performed. Moreover, the impact of water movement on mucus permeation of SEDDS
      was investigated. Different types of nanocarriers including nanoparticles and
      liposomes served as references. RESULTS: SEDDS exhibited an initial droplet size
      of 25.0 +/- 2.2, 49.5 +/- 4.6, 123.5 +/- 12.1, 226.2 +/- 93.4 and 502.9 +/- 93.7
      nm and a zeta potential of +24.4 +/- 4.6, +10.6 +/- 2.0, 0.2 +/- 3.8, -8.2 +/-
      3.4 and -35.1 +/- 2.7 mV. Log P was in the range of 1.29-2.09 and mucus
      permeation studies with these SEDDS revealed a clear correlation between droplet
      size and permeation rate. The smaller SEDDS were, the higher their mucus
      permeating properties were. Negatively charged SEDDS demonstrated a higher
      permeation rate than positively charged SEDDS. In comparison to liposomes and
      solid nanocarriers SEDDS exhibited up to 5-fold higher mucus permeating
      properties. CONCLUSION: Small droplet size and negative zeta potential of SEDDS
      could be identified as key parameters for their mucus permeating properties.

PMID- 29339248
TI  - Recent trends of nanomedicinal approaches in clinics.
AB  - Nanotechnology has become the indispensable cutting edge science providing
      solutions to many problems associated with human being. The application of
      nanotechnology associated to human health "nanomedicine" has revolutionized the
      drug delivery system by providing improved pharmacological and therapeutic
      properties of drugs. These advantageous effects of drug loaded nanocarrier
      systems are embraced by the pharmaceutical industries for the development of
      different effective nanocarriers. Currently, several drug loaded nanoformulations
      are approved by the Food and Drug Administration (FDA), and some of them are
      undergoing clinical trials for the human use. In this review, we have discussed
      the progress achieved so far for various drug loaded nanoformulations along with
      few emerging nanoformulations that are about to enter into clinical trials.

PMID- 29339249
TI  - Semifluorinated alkane based systems for enhanced corneal penetration of poorly
      soluble drugs.
AB  - Semifluorinated alkanes (SFAs) are amphiphilic liquids that can dissolve
      hydrophobic drugs to form clear solutions. This study evaluated the potential of
      two SFAs to act as vehicle for topical ocular drug delivery. After confirming
      ocular safety, an ex vivo corneal penetration model was developed to determine
      drug distribution and corneal bioavailability. Hydrophobic dye distribution in
      the different corneal layers was visualised under a confocal microscope. Corneal
      bioavailability of cyclosporine A (CsA) dissolved in perfluorobutylpentane (F4H5)
      or perfluorohexyloctane (F6H8) was compared to commercially available CsA
      ophthalmic emulsions, Restasis(r) and Ikervis(r). Precorneal residence of the
      four test vehicles containing the hydrophobic dye was also compared using an ex
      vivo corneal tissue model. Preferential accumulation of the hydrophobic dye in
      the corneal epithelium was observed with higher amounts detectable when delivered
      via the SFAs compared to Restasis or Ikervis. A significant improvement in
      corneal CsA penetration was observed after application of a single dose of 0.05%
      CsA in F4H5 and F6H8 when compared to Restasis with the area under curve over 4 h
      (AUC(0-4h)) being at least 8-fold greater for both SFAs (p < .0001). Moreover,
      the AUC(0-4h) of 0.1% CsA in F4H5 was almost 5-fold greater than Ikervis (p <
      .0001). Finally, the precorneal residence time of both SFA solutions was
      significantly longer than that of the commercial emulsions with the AUC(0-60min)
      being 2- to 11-fold greater. This study demonstrated that SFAs can significantly
      improve the local bioavailability of hydrophobic drugs by increasing corneal
      penetration as well as prolonging precorneal residence. They therefore offer a
      promising new platform for topical drug delivery to the eye.

PMID- 29339250
TI  - Discovery of novel HSP90 inhibitors that induced apoptosis and impaired
      autophagic flux in A549 lung cancer cells.
AB  - Heat shock protein 90 (HSP90) inhibition has aroused increasing enthusiasm in
      antitumor strategies in recent years. According to our previous studies, we
      synthesized a series of coumarin pyrazoline compounds HCP1-HCP6 that might be
      HSP90 inhibitors. Interactions between HCP1-HCP6 and HSP90 were examined and
      antitumor activities of them were investigated in A549 lung cancer cells. Results
      showed that all the six derivatives could interact with HSP90, in which HCP1
      exhibited the best binding ability and inhibited the activity of HSP90.
      Meanwhile, HCP1-HCP6 reduced the cell viability of A549 cells and HCP1 possessed
      the lowest IC50 value. Above all HCP1 exerted better HSP90 inhibitory and
      anticancer effects than our initially identified HSP90 inhibitor DPB. As to the
      underlying mechanism, HCP1-HCP6 not only induced apoptosis as DPB but also
      blocked autophagic flux in A549 cells. Therefore, we discovered a novel HSP90
      inhibitor HCP1 that had better biological activity and provided us a useful tool
      to explore the underlying mechanism of lung cancer therapy.

PMID- 29339251
TI  - Quinoxaline derivatives as new inhibitors of coxsackievirus B5.
AB  - Enteroviruses are among the most common and important human pathogens for which
      there are no specific antiviral agents approved by the US Food and Drug
      Administration so far. Particularly, coxsackievirus infections have a worldwide
      distribution and can cause many important diseases. We here report the synthesis
      of new 14 quinoxaline derivatives and the evaluation of their cytotoxicity and
      antiviral activity against representatives of ssRNA, dsRNA and dsDNA viruses.
      Promisingly, three compounds showed a very potent and selective antiviral
      activity against coxsackievirus B5, with EC50 in the sub-micromolar range (0.3
      0.06 MUM). A combination of experimental techniques (i.e. virucidal activity,
      time of drug addition and adsorption assays) and in silico modeling studies were
      further performed, aiming to understand the mode of action of the most active,
      selective and not cytotoxic compound, the ethyl 4-[(2,3-dimethoxyquinoxalin-6
      yl)methylthio]benzoate (6).

PMID- 29339252
TI  - Structure-based design of human immuno- and constitutive proteasomes inhibitors.
AB  - Starting from the X-ray structure of our previous tripeptidic linear mimics of
      TMC-95A in complex with yeast 20S proteasome, we introduced new structural
      features to induce a differential inhibition between human constitutive and
      immunoproteasome 20S particles. Libraries of 24 tripeptidic and 6 dipeptidic
      derivatives were synthesized. The optimized preparation of 3-hydroxyoxindolyl
      alanine residues from tryptophan and their incorporation in peptides were
      described. Several potent inhibitors of human constitutive proteasome and
      immunoproteasome acting at the nanomolar level (IC50 = 7.1 nM against the
      chymotrypsin-like activity for the best inhibitor) were obtained. A cytotoxic
      effect at the submicromolar level was observed against 6 human cancer cell lines.

PMID- 29339253
TI  - Design, synthesis and bioevalucation of novel 2,3-dihydro-1H-inden-1-amine
      derivatives as potent and selective human monoamine oxidase B inhibitors based on
      rasagiline.
AB  - Parkinson's disease (PD) is associated with elevated levels of hMAO-B in the
      brain, and MAO-B has been recognized a successful target for developing anti-PD
      drugs. Herein we report rasagiline derivatives as novel potent and selective hMAO
      B inhibitors. They were designed by employing fragment-based drug design strategy
      to link rasagiline and hydrophobic fragments, which may target a hydrophobic
      pocket in the entrance cavity of hMAO-B. Different linkers such as -OCH2-, -SCH2
      , -OCH2CH2-, -OCH2CH2O-, -OCH2CH2CH2O- were tried. A promising selective hMAO-B
      inhibitor D14 with similar inhibitory activity as rasagiline and improved isoform
      selectivity was yielded. The selectivity profile of compounds reported herein
      suggests that we can further develop more potent hMAO-B inhibitors with high
      isoform selectivity through this strategy.

PMID- 29339254
TI  - Design, synthesis, biological evaluation and docking studies of new 3-(4,5
      dihydro-1H-pyrazol/isoxazol-5-yl)-2-phenyl-1H-indole derivatives as potent
      antioxidants and 15-lipoxygenase inhibitors.
AB  - New candidates of 3-(4,5-dihydro-1H-pyrazol/isoxazol-5-yl)-2-phenyl-1H-indole
      derivatives (4-7) were designed combining the pyrazoline/isoxazoline heterocycles
      and 2-phenylindole to explore its potential as 15-lipoxygenase (15-LOX)
      inhibitors. The design of the new derivatives was based on utilizing the
      antioxidant properties of pyrazoline, 2-phenylindole and the good 15-LOX
      inhibition properties of indolylpyrazoline. The derivatives were synthesized
      adopting simple and laboratory friendly reaction conditions to give the target
      compounds in quantitative yields. The resulting indolylpyrazolines/isoxazolines
      were evaluated as antioxidants against 2,2-diphenyl-1-picrylhydrazyl (DPPH),
      nitric oxide (NO) and superoxide dismutase (SOD); indolylpyrazoline (4b) was the
      most potent antioxidant against SOD assay (IC50 = 1.78 MUM) to be superior to
      ascorbic by 2 folds. Consistently, (4b) was the most potent inhibitor when tested
      against Soybean 15-LOX (IC50 = 3.84 MUM) excelling quercetin as standard
      inhibitor by 1.8 folds. Some of the new derivatives were docked into the active
      binding site of human 15-LOX (PDB entry 4NRE) emphasizing the most potent
      derivative (4b) and the least potent one (4c). Docking solutions of compounds
      (4b), (4c), (5b) and (6c) revealed that (4b) was the only compound that got
      stabilized into the catalytic pocket of enzyme by pi-cation interaction with the
      catalytic Fe+ and formation of one hydrogen bond with Ile 676 amino acid. Other
      derivatives including the least potent one variably got stabilized into the
      active binding pocket by pi-cation interaction with the catalytic Fe+ but failed
      to form hydrogen bond with Ile 676. For the future optimization of the generated
      inhibitors, (i) antioxidant activity against SOD, (ii) the inhibitor
      stabilization by pi-cation interaction with the catalytic Fe+3 and (iii)
      formation of hydrogen bond with Ile 676 should be regarded.

PMID- 29339255
TI  - Design, synthesis and biological evaluation of LX2343 derivatives as
      neuroprotective agents for the treatment of Alzheimer's disease.
AB  - A series of LX2343 derivatives were designed, synthesized and evaluated as
      neuroprotective agents for Alzheimer's disease (AD) in vitro. Most of the
      compounds displayed potent neuroprotective activities. Especially for compound
      A6, exhibited a remarkable EC50 value of 0.22 MUM. Further investigation
      demonstrated that compound A6 can significantly reduce Abeta production and
      increase Abeta clearance, and alleviate Tau hyperphosphorylation. Most
      importantly, compound A6 could ameliorate learning and memory impairments in
      APP/PS1 transgenic mice. The present study evidently showed that compound A6 is a
      potent neuroprotective agent and might serve as a promising lead candidate for
      the treatment of Alzheimer's disease.

PMID- 29339256
TI  - The PBII gene of the human salivary proline-rich protein P-B produces another
      protein, Q504X8, with an opiorphin homolog, QRGPR.
AB  - OBJECTIVES: The NCBI gene database and human-transcriptome database for
      alternative splicing were used to determine the expression of mRNAs for P-B
      (SMR3B) and variant form of P-B. The translational product from the former mRNA
      was identified as the protein named P-B, whereas that from the latter has not yet
      been elucidated. In the present study, we investigated the expression of P-B and
      its variant form at the protein level. DESIGN: To identify the variant protein of
      P-B, (1) cationic proteins with a higher isoelectric point in human pooled whole
      saliva were purified by a two dimensional liquid chromatography; (2) the peptide
      fragments generated from the in-solution of all proteins digested with trypsin
      separated and analyzed by MALDI-TOF-MS; and (3) the presence or absence of P-B in
      individual saliva was examined by 15% SDS-PAGE. RESULTS: The peptide sequences
      (I37PPPYSCTPNMNNCSR52, C53HHHHKRHHYPCNYCFCYPK72, R59HHYPCNYCFCYPK72 and
      H60HYPCNYCFCYPK72) present in the variant protein of P-B were identified. The
      peptide sequence (G6PYPPGPLAPPQPFGPGFVPPPPPPPYGPGR36) in P-B (or the variant) and
      sequence (I37PPPPPAPYGPGIFPPPPPQP57) in P-B were identified. The sum of the
      sequences identified indicated a 91.23% sequence identity for P-B and 79.76% for
      the variant. There were cases in which P-B existed in individual saliva, but
      there were cases in which it did not exist in individual saliva. CONCLUSIONS: The
      variant protein is produced by excising a non-canonical intron (CC-AC pair) from
      the 3'-noncoding sequence of the PBII gene. Both P-B and the variant are subject
      to proteolysis in the oral cavity.

PMID- 29339257
TI  - Changes in the concentrations of inflammatory and oxidative status biomediators
      (MIP-1 alpha, PMN elastase, MDA, and IL-12) in depressed patients with and
      without posttraumatic stress disorder.
AB  - BACKGROUND: Both proinflammatory cytokines and oxidative stress are considered an
      imbalance between the cellular production of reactive oxygen species and the
      antioxidant defense mechanisms. An inflammatory response that occurs in
      depression leads to a synergy between pro-inflammatory cytokines and oxidative
      stress. This synergy induces common signal transduction pathways that boost the
      inflammatory cascade. The object of this study was to assess the concentrations
      of inflammatory and oxidative status biomediators such as MIP-1alpha, PMN
      elastase, MDA, and IL-12 in depressed patients with and without posttraumatic
      stress disorder (PTSD), and with PTSD alone. METHODS: The number of participants
      enrolled in the study was 460. Out of them, 420 were determined to be suffering
      from depression, and 40 (20 males and 20 females) comprised the control group.
      The subjects were divided into groups, each consisting of 60 participants (30
      males and 30 females) with: mild depression (MD), moderate depression (MOD),
      severe depression (SeD), MD and PTSD (MD+PTSD), MOD and PTSD (MOD+PTSD), SeD and
      PTSD (Sed+PTSD), and PTSD alone. At 7:00 a.m. all patients had blood samples
      collected to assess serum concentrations of the studied parameters using the
      Elisa method. RESULTS: Depression became more severe as the concentration levels
      of MIP-1alpha, PMN elastase, MDA, and IL-12 changed. CONCLUSION: Studied
      parameters can be used as markers of chronic stress in both depression and PTSD,
      either comorbid or alone, to make an early diagnosis and evaluate disease
      severity. Revealed changes confirm the presence of a biological response in
      depression.

PMID- 29339258
TI  - Relationship between very early brain structure and neuromotor, neurological and
      neurobehavioral function in infants born <31 weeks gestational age.
AB  - AIM: This study aimed to examine associations between structural MRI and
      concurrent motor, neurological and neurobehavioral measures at 30-32 weeks
      postmenstrual age (PMA; 'Early'), and at term equivalent age ('Term'). METHOD: In
      this prospective cohort study, infants underwent Early MRI (n = 119; 73 male;
      median 32 weeks 1 day PMA) and Term MRI (n = 102; 61 male; median 40 weeks 4 days
      PMA) at 3 T. Structural images were scored generating white matter (WM), cortical
      gray matter, deep gray matter, cerebellar and global brain abnormality scores.
      Clinical measures were General Movements Assessment (GMs), Hammersmith Neonatal
      Neurological Examination (HNNE) and NICU Neonatal Neurobehavioral Scale (NNNS).
      The Premie-Neuro was administered Early and the Test of Infant Motor Performance
      (TIMP) and a visual assessment at Term. RESULTS: Early MRI cerebellar scores were
      strongly associated with neurological components of HNNE (reflexes), NNNS
      (Hypertonicity), the Premie-Neuro neurological subscale (regression coefficient
      beta = -0.06; 95% confidence interval CI = -0.09, -0.04; p < .001) and cramped
      synchronized GMs (beta = 1.10; 95%CI = 0.57, 1.63; p < .001). Term MRI WM and
      global scores were strongly associated with the TIMP (WM beta = -1.02; 95%CI = 
      1.67, -0.36; p = .002; global beta = -1.59; 95%CI = -2.62, -0.56; p = .001).
      INTERPRETATION: Brain structure on Early and Term MRI was associated with
      concurrent motor, neurological and neurobehavioral function in very preterm
      infants.

PMID- 29339259
TI  - Perturbations of gut microbiome genes in infants with atopic dermatitis according
      to feeding type.
AB  - BACKGROUND: Perturbations of the infant gut microbiota can shape development of
      the immune system and link to the risk of allergic diseases. OBJECTIVE: We sought
      to understand the role of the gut microbiome in patients with atopic dermatitis
      (AD). The metagenome of the infant gut microbiome was analyzed according to
      feeding types. METHODS: Composition of the gut microbiota was analyzed in fecal
      samples from 129 infants (6 months old) by using pyrosequencing, including 66
      healthy infants and 63 infants with AD. The functional profile of the gut
      microbiome was analyzed by means of whole-metagenome sequencing (20 control
      subjects and 20 patients with AD). In addition, the total number of bacteria in
      the feces was determined by using real-time PCR. RESULTS: The gut microbiome of 6
      month-old infants was different based on feeding types, and 2 microbiota groups
      (Bifidobacterium species-dominated and Escherichia/Veillonella species-dominated
      groups) were found in breast-fed and mixed-fed infants. Bacterial cell amounts in
      the feces were lower in infants with AD than in control infants. Although no
      specific taxa directly correlated with AD in 16S rRNA gene results, whole
      metagenome analysis revealed differences in functional genes related to immune
      development. The reduction in genes for oxidative phosphorylation,
      phosphatidylinositol 3-kinase-Akt signaling, estrogen signaling, nucleotide
      binding domain-like receptor signaling, and antigen processing and presentation
      induced by reduced colonization of mucin-degrading bacteria (Akkermansia
      muciniphila, Ruminococcus gnavus, and Lachnospiraceae bacterium 2_1_58FAA) was
      significantly associated with stunted immune development in the AD group compared
      with the control group (P < .05). CONCLUSIONS: Alterations in the gut microbiome
      can be associated with AD because of different bacterial genes that can modulate
      host immune cell function.

PMID- 29339261
TI  - Mumps infection but not childhood vaccination induces persistent polyfunctional
      CD8+ T-cell memory.

PMID- 29339260
TI  - The complement system in the airway epithelium: An overlooked host defense
      mechanism and therapeutic target?

PMID- 29339262
TI  - The long-term physical and psychological health impacts of flooding: A systematic
      mapping.
AB  - BACKGROUND: Flooding has caused significant and wide ranging long-term health
      impacts for affected populations. However, until now, the long-term health
      outcomes, epidemiological trends and specific impact factors of flooding had not
      been identified. In this study, the relevant literature was systematically mapped
      to create the first synthesis of the evidence of the long-term health impacts of
      flooding. METHODS: The systematic mapping method was used to collect and
      categorize all the relevant literature. A study was included if it had a
      description or measurement of health impacts over six months after flooding. The
      search was limited to peer reviewed articles and grey literature written in
      English, published from 1996 to 2016. RESULTS: A total of 56 critical articles
      were extracted for the final map, including 5 qualitative and 51 quantitative
      studies. Most long-term studies investigated the psychological impacts of
      flooding, including PTSD, depression, anxiety, psychiatric disorders, sleep
      disorder and suicide. Others investigated the physiological impacts, including
      health-related quality of life, acute myocardial infarction, chronic diseases,
      and malnutrition. Social support was proved to be protective factors that can
      improve health outcomes in the long-term after flooding. To date, there have been
      relatively few reviews had focused on the long-term health impacts of flooding.
      This study coded and catalogued the existing evidence across a wide range of
      variables and described the long-term health consequences within a conceptual
      map. DISCUSSION AND CONCLUSIONS: Although there was no boundary between the short
      term and the long-term impacts of flooding, the identified health outcomes in
      this systematic mapping could be used to define long-term health impacts. The
      studies showed that the prevalence of psychological diseases had a reversed
      increasing trend occurred even in the long-term in relatively poor post-flooding
      environments. Further cohort or longitudinal research focused on disability,
      chronic diseases, relocation population, and social interventions after flooding,
      are urgently required.

PMID- 29339263
TI  - Impact of organic amendments (biochar, compost and peat) on Cd and Zn mobility
      and solubility in contaminated soil of the Campine region after three years.
AB  - To determine the long-term impact of organic amendments on metal (Cd and Zn)
      immobilization, soil from the Campine region was amended with holm oak-derived
      biochar, compost, and peat, and monitored over a 3-year period. Pot experiments
      were conducted by mixing the amendments independently at 2% and 4% (g/g) with the
      soil. The mobility and solubility of metals in the treatments were assessed by
      means of rhizon soil moisture samplers, sequential BCR extractions, and diffusive
      gradient in thin films (DGT). Over the three-year period, the 2% biochar addition
      resulted in an average decrease in pore water concentration of 40% for Cd and 48%
      for Zn whereas the 4% addition led to an average decrease of 66% for Cd and 77%
      for Zn. The immobilization effect in the biochar treatments was attributed to the
      consistently higher pH and lower concentrations of dissolved organic carbon (DOC)
      in the soil. The latter may have been caused by sorption of DOC onto the surface
      of biochar thereby increasing its negatively charged functional groups that are
      able to sorb cations. On the other hand, compost and peat had the unwanted effect
      of significantly increasing the concentrations of Cd and Zn in the soil pore
      water. This was partly due to the formation of soluble organo-metallic complexes
      as significantly higher DOC concentrations were found in the compost and peat
      treatments. Results from the DGT measurements, after a 24 h deployment time,
      revealed a low resupply (R <= 0.4) of Cd and Zn from the solid phase to the soil
      solution in both amended and unamended soil. This suggests a case of slow metal
      desorption kinetics in the soil that was relatively unchanged by the presence of
      organic amendments.

PMID- 29339264
TI  - Source apportionment of soil heavy metals using robust absolute principal
      component scores-robust geographically weighted regression (RAPCS-RGWR) receptor
      model.
AB  - The traditional source apportionment models, such as absolute principal component
      scores-multiple linear regression (APCS-MLR), are usually susceptible to
      outliers, which may be widely present in the regional geochemical dataset.
      Furthermore, the models are merely built on variable space instead of
      geographical space and thus cannot effectively capture the local spatial
      characteristics of each source contributions. To overcome the limitations, a new
      receptor model, robust absolute principal component scores-robust geographically
      weighted regression (RAPCS-RGWR), was proposed based on the traditional APCS-MLR
      model. Then, the new method was applied to the source apportionment of soil metal
      elements in a region of Wuhan City, China as a case study. Evaluations revealed
      that: (i) RAPCS-RGWR model had better performance than APCS-MLR model in the
      identification of the major sources of soil metal elements, and (ii) source
      contributions estimated by RAPCS-RGWR model were more close to the true soil
      metal concentrations than that estimated by APCS-MLR model. It is shown that the
      proposed RAPCS-RGWR model is a more effective source apportionment method than
      APCS-MLR (i.e., non-robust and global model) in dealing with the regional
      geochemical dataset.

PMID- 29339265
TI  - Spatio-temporal distribution of soil nitrogen in Poyang lake ecological economic
      zone (South-China).
AB  - Revealing the spatio-temporal distribution of soil nitrogen (N) contributes to N
      management and prevention of N pollution. The objective of this work is to study
      the spatio-temporal distribution of soil N and their driving factors in the
      topsoil (0-20 cm) of farmland in Yugan county, China in 1982 and 2012. Data were
      collected from 200 sampling sites of the second national soil survey in Yugan in
      1982 and 423 sampling sites of the soil testing and formula fertilization project
      in 2012. On average total N (TN) and available N (AN) significantly increased
      from 1.50 g kg-1 and 153.04 mg kg-1 in 1982 to 1.58 g kg-1 and 179.75 mg kg-1 in
      2012, respectively. The distance of spatial autocorrelation for TN increased from
      2.79 to 6.18 km and from 2.97 to 18.00 km for AN from 1982 to 2012. The
      nugget/sill ratio for TN (0.472 in 1982 and 0.581 in 2012) indicated that soil TN
      driving by natural characteristics in 1982 to human activities in 2012. The
      nugget/sill ratio for soil AN (0.471 in 1982 and 0.688 in 2012) indicated that
      soil AN is more influenced by human activities. The major factors driving the
      spatio-temporal distribution of soil N was N application rate. To promote the
      sustainable development of agriculture and eco-environment, we should improve the
      awareness of farmers on chemical fertilizers (particularly N) and the level of N
      fertilizer management, increase the use of manure and organic fertilizer and
      facilitate rational fertilization by farmers.

PMID- 29339266
TI  - Long-term trend analysis on total and extreme precipitation over Shasta Dam
      watershed.
AB  - California's interconnected water system is one of the most advanced water
      management systems in the world, and understanding of long-term trends in
      atmospheric and hydrologic behavior has increasingly being seen as vital to its
      future well-being. Knowledge of such trends is hampered by the lack of long
      period observation data and the uncertainty surrounding future projections of
      atmospheric models. This study examines historical precipitation trends over the
      Shasta Dam watershed (SDW), which lies upstream of one of the most important
      components of California's water system, Shasta Dam, using a dynamical
      downscaling methodology that can produce atmospheric data at fine time-space
      scales. The Weather Research and Forecasting (WRF) model is employed to
      reconstruct 159years of long-term hourly precipitation data at 3km spatial
      resolution over SDW using the 20th Century Reanalysis Version 2c dataset. Trend
      analysis on this data indicates a significant increase in total precipitation as
      well as a growing intensity of extreme events such as 1, 6, 12, 24, 48, and 72
      hour storms over the period of 1851 to 2010. The turning point of the increasing
      trend and no significant trend periods is found to be 1940 for annual
      precipitation and the period of 1950 to 1960 for extreme precipitation using the
      sequential Mann-Kendall test. Based on these analysis, we find the trends at the
      regional scale do not necessarily apply to the watershed-scale. The sharp
      increase in the variability of annual precipitation since 1970s is also detected,
      which implies an increase in the occurrence of extreme wet and dry conditions.
      These results inform long-term planning decisions regarding the future of Shasta
      Dam and California's water system.

PMID- 29339267
TI  - Effects of exotic plantation forests on soil edaphon and organic matter
      fractions.
AB  - There is uncertainty and limited knowledge regarding soil microbial properties
      and organic matter fractions of natural secondary forest accompanying chemical
      environmental changes of replacement by pure alien plantation forests in a hilly
      area of southwest of Sichuan province China. The aim of this study was to
      evaluate the impact of natural secondary forest (NSF) to pure Cryptomeria
      fortunei forest (CFF) and Cunninghamia lanceolata forest (CLF) on soil organic
      fractions and microbial communities. The results showed that the soil total
      phospholipid fatty acids (PLFAs), total bacteria and fungi, microbial carbon
      pool, organic recalcitrant carbon (C) and (N) fractions, soil microbial quotient
      and labile and recalcitrant C use efficiencies in each pure plantation were
      significantly decreased, but their microbial N pool, labile C and N pools, soil
      carbon dioxide efflux, soil respiratory quotient and recalcitrant N use
      efficiency were increased. An RDA analysis revealed that soil total PLFAs, total
      bacteria and fungi and total Gram-positive and Gram-negative bacteria were
      significantly associated with exchangeable Al3+, exchangeable acid, Al3+,
      available P and Mg2+ and pH, which resulted into microbial functional changes of
      soil labile and recalcitrant substrate use efficiencies. Modified microbial C-
      and N-use efficiency due to forest conversion ultimately meets those of rapidly
      growing trees in plantation forests. Enlarged soil labile fractions and soil
      respiratory quotients in plantation forests would be a potential positive effect
      for C source in the future forest management. Altogether, pure plantation
      practices could provoke regulatory networks and functions of soil microbes and
      enzyme activities, consequently leading to differentiated utilization of soil
      organic matter fractions accompanying the change in environmental factors.

PMID- 29339268
TI  - Incidence of Second Primary Malignancies after Autologous Transplantation for
      Multiple Myeloma in the Era of Novel Agents.
AB  - The advent of novel agents for multiple myeloma (MM) is cause for a re
      examination of the incidence of second primary malignancies (SPMs). We examined
      the SPM rate in MM patients who were enrolled in the prospective observational
      CALM (Collaboration to Collect Autologous Transplant outcome in Lymphoma and
      Myeloma) study. Between 2008 and 2012, 3204 patients with MM underwent a first
      autologous hematopoietic stem cell transplantation. Plerixafor was used as a
      mobilizing agent for patients with poor (or potentially poor) stem cell
      mobilization as defined by the respective centers. A total of 135 patients
      developed SPMs, with a cumulative incidence of 5.3% (95% confidence interval, 4.4
      to 6.3) at 72 months. Ninety-four patients developed solid tumors, 30 developed
      hematologic malignancies, and 11 developed an SPM of an unknown type. The
      cumulative incidence of known hematologic and solid malignancies were 1.4% and
      3.6%, respectively, at 72 months. In a univariate analysis, use of radiotherapy,
      type of induction regimen, hematopoietic stem cell dose, poor mobilizer status,
      plerixafor use, and sex did not influence the cumulative incidence of SPMs. Only
      age over 65 years was statistically associated with an increased incidence.
      Overall, the incidence of SPMs was comparable to earlier estimations of SPMs in
      MM.

PMID- 29339269
TI  - Phase 2 Study of an Intravenous Busulfan and Melphalan Conditioning Regimen for
      Autologous Stem Cell Transplantation in Patients with Multiple Myeloma (KMM150).
AB  - This prospective study evaluated the efficacy and toxicity of intravenous
      busulfan and melphalan as a conditioning regimen for autologous stem cell
      transplantation (ASCT) in patients with multiple myeloma (MM). A total of 99
      patients with MM, enrolled between January 2013 and March 2016, received
      intravenous busulfan (9.6 mg/kg) and melphalan (140 mg/m2) before ASCT. The
      median time to transplant was 6.2 months, and 90 (90.9%) patients underwent ASCT
      within 12 months of the diagnosis. The overall response rate after ASCT was
      94.0%, including 43.5% with a stringent complete response/complete response,
      27.3% with very good partial response, and 23.2% with partial response. The most
      common severe nonhematologic toxicity (grade 3 to 4) was infection (26.3%) and
      stomatitis (15.2%). Three (3.2%) patients developed veno-occlusive disease. No
      treatment-related mortality was observed. After a median follow-up of 26.1
      months, the median progression-free survival was 27.2 months (range, 13.0 to 41.4
      months) and median overall survival was not reached. In conclusion, a
      conditioning regimen of intravenous busulfan and melphalan was effective and
      tolerable. ClinicalTrials.gov. number: NCT01923935.

PMID- 29339270
TI  - Proceedings From the Fourth Haploidentical Stem Cell Transplantation Symposium
      (HAPLO2016), San Diego, California, December 1, 2016.
AB  - The resurgence of haploidentical stem cell transplantation (HaploSCT) over the
      last decade is one of the most important advances in the field of hematopoietic
      stem cell transplantation (HSCT). The modified platforms of T cell depletion
      either ex vivo (CD34+ cell selection, "megadoses" of purified CD34+ cells, or
      selective depletion of T cells) or newer platforms of in vivo depletion of T
      cells, with either post-transplantation high-dose cyclophosphamide or intensified
      immune suppression, have contributed to better outcomes, with survival similar to
      that in HLA-matched donor transplantation. Further efforts are underway to
      control viral reactivation using modified T cells, improve immunologic
      reconstitution, and decrease the relapse rate post-transplantation using donor
      derived cellular therapy products, such as genetically modified donor lymphocytes
      and natural killer cells. Improvements in treatment-related mortality have
      allowed the extension of haploidentical donor transplants to patients with
      hemoglobinopathies, such as thalassemia and sickle cell disease, and the possible
      development of platforms for immunotherapy in solid tumors. Moreover, combining
      HSCT from a related donor with solid organ transplantation could allow early
      tapering of immunosuppression in recipients of solid organ transplants and
      hopefully prevent organ rejection in this setting. This symposium summarizes some
      of the most important recent advances in HaploSCT and provides a glimpse in the
      future of fast growing field.

PMID- 29339271
TI  - Early Increase in Complement Terminal Pathway Activation Marker sC5b-9 Is
      Predictive for the Development of Thrombotic Microangiopathy after Stem Cell
      Transplantation.
AB  - Hematopoietic stem cell transplantation (HSCT)-associated thrombotic
      microangiopathy (TA-TMA) is a multifactorial complication, and its prediction is
      largely unresolved. Our aim was to analyze changes of complement profile after
      HSCT to identify potential markers of TA-TMA development. Thirty-three
      consecutive pediatric patients (9.6 +/- 4.4 years old) who underwent allogeneic
      HSCT due to malignant (n = 17) or nonmalignant (n = 16) indications were included
      in this study. Graft-versus-host disease (GVHD) was diagnosed using Glucksberg
      criteria, viral reactivation was monitored, 5 different TA-TMA diagnostic
      criteria were applied, and all important clinical and laboratory parameters of TA
      TMA activity were registered. Complement pathway activities, components and
      terminal pathway activation marker (sC5b-9) levels were systematically measured
      before transplantation and on days 28, 56, and 100 after HSCT. During the first
      100 days after HSCT, 1 of 33 patients died (day 50, multiple organ failure),
      whereas 10 subjects met the criteria for TA-TMA, typically on day 61 (range, 16
      to 98 days). TA-TMA was preceded by acute GVHD in 3 of 10 patients, by viral
      reactivation in 2 of 10, or by both in 4 of 10 cases. Baseline sC5b-9 levels did
      not differ in patients without (200 [interquartile range, 144 to 266] ng/mL), or
      with (208 [interquartile range, 166 to 271] ng/mL) subsequent TA-TMA; however, on
      day 28 significant differences were observed (201 [interquartile range, 185 to
      290] ng/mL versus 411 [interquartile range, 337 to 471] ng/mL; P = .004).
      Importantly, all 10 patients with TMA showed increase in sC5b-9 level from
      baseline level to day 28, whereas in patients without TMA the same tendency was
      observed for only 9 of 23 patients (P = .031). No additional complement
      parameters were closely associated with the development of TA-TMA. Development of
      TA-TMA occurred in 30% of our patients, typically after GVHD and/or viral
      reactivation. However, early raise of sC5b-9 activation marker was predictive for
      later development of TA-TMA, and should therefore be considered as an alarming
      sign necessitating a careful monitoring of all TA-TMA activity markers. Further
      studies enrolling a higher number of patients are necessary to determine if
      terminal pathway activation is an independent predictor of TA-TMA.

PMID- 29339272
TI  - An Old Friend Is Trouble for Double-Expressor and Double-Hit Lymphoma.

PMID- 29339273
TI  - Electrolyte selection and microbial toxicity for electrochemical oxidative water
      treatment using a boron-doped diamond anode to support site specific
      contamination incident response.
AB  - Intentional and unintentional contamination incidents, such as terrorist attacks,
      natural disasters, and accidental spills, can result in large volumes of
      contaminated water. These waters may require pre-treatment before disposal and
      assurances that treated waters will not adversely impact biological processes at
      wastewater treatment facilities, or receiving waters. Based on recommendations of
      an industrial workgroup, this study addresses such concerns by studying
      electrochemical advanced oxidation process (EAOP) pre-treatment for contaminated
      waters, using a boron-doped diamond (BDD) anode, prior to discharge to wastewater
      treatment facilities. Reaction conditions were investigated, and microbial
      toxicity was assessed using the Microtox(r) toxicity assay and the Nitrification
      Inhibition test. A range of contaminants were studied including herbicides,
      pesticides, pharmaceuticals and flame retardants. Resulting toxicities varied
      with supporting electrolyte from 5% to 92%, often increasing, indicating that
      microbial toxicity, in addition to parent compound degradation, should be
      monitored during treatment. These toxicity results are particularly novel because
      they systematically compare the microbial toxicity effects of a variety of
      supporting electrolytes, indicating some electrolytes may not be appropriate in
      certain applications. Further, these results are the first known report of the
      use of the Nitrification Inhibition test for this application. Overall, these
      results systematically demonstrate that anodic oxidation using the BDD anode is
      useful for addressing water contaminated with refractory organic contaminants,
      while minimizing impacts to wastewater plants or receiving waters accepting EAOP
      treated effluent. The results of this study indicate nitrate can be a suitable
      electrolyte for incident response and, more importantly, serve as a baseline for
      site specific EAOP usage.

PMID- 29339274
TI  - Geochemical sources of metal contamination in a coal mining area in Chhattisgarh,
      India using lead isotopic ratios.
AB  - A geochemical study of the trace metals and lead isotopic ratios of soil and
      sediments in Korba, Chhattisgarh, India is presented here for the first time.
      Korba, the nation's 'power hub' is also the fifth among its eighty-eight most
      critically polluted industrial hotspots. A very high mean concentration (in mg kg
      1) of V (308), Cr (567), Mn (3442), Co (92), Cu (218), Zn (426), Pb (311), Th
      (123) and U (32) characterized the sediments of the studied area with mean Igeo
      values of the trace metals ranging from -2.29 to 3.27. In the two-ratio scatter
      Pb isotope plot of the different environmental matrices, except for human blood,
      coal, soil, sediments, non-washed leaves, flyash and diesel overlapped linearly
      in the mixing line between diesel as the highest anthropogenic end member and a
      core sediment fraction representing its geogenic counterpart. The mean
      207Pb/206Pb Pb ratio decreased in the order of diesel (0.9012) > flyash (0.8757)
      > coal (0.8498) soils and sediments (0.8374) > lowest core sediment fraction
      (0.8017). Principal Component Analysis (PCA) of the trace metal data extracted V,
      Cr, Cu, Zn, Pb, U and Th in the first component PC1. The northeastern part of the
      study area revealed major hotspots of V, Cu, Co, Zn and Pb near the flyash dykes
      of the power stations. Human blood used as a biomarker for Pb pollution in this
      study had a mean blood lead level of 28 MUg/dl with a distinctive high
      207Pb/206Pb ratio of 0.8828.

PMID- 29339275
TI  - Biochar-based functional materials in the purification of agricultural
      wastewater: Fabrication, application and future research needs.
AB  - Nowadays, agricultural contamination is becoming more and more serious due to the
      rapid growth of agricultural industry, which discharged antibiotics, pesticides
      or toxic metals into farmlands. A large number of researchers have applied
      biochar-based functional materials to the treatment of agricultural wastewater
      contamination. Meanwhile, biochar has also proved to be a very promising and
      effective technology in water purification field due to its various beneficial
      properties (e.g., cost effective, high specific surface area, and surface
      reactive groups). The focus of this review is to highlight the fabrication
      methods and application of biochar-based functional materials with the removal of
      different agricultural contaminants, and discuss the underlying mechanisms.
      However, the application of biochar-based functional materials is currently under
      its infancy, with the main hindrance is identified as the gap between laboratory
      scale and field application, immaturity of engineered biochar production
      technologies, and lack of quality standards. In order to fill these knowledge
      gaps, more efforts should be made to pay for the relevant research in future
      studies.

PMID- 29339276
TI  - Reliability of oscillometric central blood pressure and central systolic loading
      in individuals over 50 years: Effects of posture and fasting.
AB  - BACKGROUND AND AIMS: The between-day reliability of oscillometric pulse wave
      analysis has been demonstrated in a young, healthy population but not in an older
      sample. This study examined the between-day reliability of the SphygmoCor XCEL in
      individuals over 50 years. As blood pressure is measured in a range of postures
      and fasting states (supine/seated, fasted/non-fasted), this study also
      investigated the effect of these variables on central blood pressure and central
      systolic loading. METHODS: Fifty-one adults (m = 21; age 57 +/- 6.4 y) were
      tested on three mornings in supine and seated conditions and in fasted and non
      fasted states. Data was analysed as a whole and for normotensive (n = 25) and
      hypertensive participants (n = 26). RESULTS: SphygmoCor XCEL demonstrated strong
      reliability in the whole sample for central systolic and diastolic blood
      pressures, augmentation index (AIx) and AIx75 (ICC = 0.77-0.95). Significant
      interaction effects were observed in central diastolic blood pressure, central
      pulse pressure, augmentation index (AIx) and AIx75 (p < 0.05; etap2 = 0.10-0.23).
      Fasting state had a greater influence on central pressures in a seated than
      supine posture, but a greater effect on central systolic loading measures in a
      supine posture. CONCLUSIONS: The SphygmoCor XCEL is a reliable tool to assess
      central haemodynamic variables in an older population. It would be pertinent for
      clinicians and researchers to record central measures in a supine posture to
      minimise the effects of food consumption. Conversely, the assessment of central
      systolic loading should occur in a seated condition to minimise the influence of
      varying fasting states.

PMID- 29339277
TI  - Molecular phylogeny of Systellognatha (Plecoptera: Arctoperlaria) inferred from
      mitochondrial genome sequences.
AB  - The infraorder Systellognatha is the most species-rich clade in the insect order
      Plecoptera and includes six families in two superfamilies: Pteronarcyoidea
      (Pteronarcyidae, Peltoperlidae, and Styloperlidae) and Perloidea (Perlidae,
      Perlodidae, and Chloroperlidae). To resolve the debatable phylogeny of
      Systellognatha, we carried out the first mitochondrial phylogenetic analysis
      covering all the six families, including three newly sequenced mitogenomes from
      two families (Perlodidae and Peltoperlidae) and 15 published mitogenomes. The
      three newly reported mitogenomes share conserved mitogenomic features with other
      sequenced stoneflies. For phylogenetic analyses, we assembled five datasets with
      two inference methods to assess their influence on topology and nodal support
      within Systellognatha. The results indicated that inclusion of the third codon
      positions of PCGs, exclusion of rRNA genes, the use of nucleotide datasets and
      Bayesian inference could improve the phylogenetic reconstruction of
      Systellognatha. The monophyly of Perloidea was supported in the mitochondrial
      phylogeny, but Pteronarcyoidea was recovered as paraphyletic and remained
      controversial. In this mitochondrial phylogenetic study, the relationships within
      Systellognatha were recovered as (((Perlidae + (Perlodidae + Chloroperlidae)) +
      (Pteronarcyidae + Styloperlidae)) + Peltoperlidae).

PMID- 29339278
TI  - Amphotericin B loaded sulfonated chitosan nanoparticles for targeting macrophages
      to treat intracellular Candida glabrata infections.
AB  - The current study assesses the potential of functionalised chitosan nanoparticles
      (CNPs) for proficient macrophage delivery of amphotericin B (AmpB) for the
      management of Candida glabrata fungemia. Chitosan was functionalised by the
      method of sulfation by using chlorosulfonic acid and the developed compound was
      confirmed by FTIR, 1H NMR and degree of sulfation and CHNS analysis. Amphotericin
      B encapsulated sulfated chitosan (AmpB-SCNPs), when characterized showed a
      hydrodynamic diameter of 310 +/- 14 nm and zeta potential of 41.5 +/- 2 mV. The
      safety of AmpB-SCNPs was established by the alamar cytotoxicity assay in
      nanoparticle treated macrophages following 24 h incubation. The AmpB-SCNPs showed
      a significant increase in the reduction of C. glabrata in comparison with the
      bare AmpB and AmpB-CNPs (55.2 and 42.7 vs 11.12 cfu/ml) indicating that AmpB
      SCNPs could be a promising carrier for specific delivery of AmpB to macrophages
      for effective treatment of Candida glabrata fungemia.

PMID- 29339279
TI  - Green synthesis of antimicrobial and antitumor N,N,N-trimethyl chitosan
      chloride/poly (acrylic acid)/silver nanocomposites.
AB  - The present study is imported to solve two critical problems we face in our daily
      life which are microbial pollution and colon cancer. One pot green synthesis of a
      water soluble polyelectrolyte complex (PEC) between cationic polysaccharide as
      N,N,N-trimethyl chitosan chloride (TMC) and anionic polymer as poly (acrylic
      acid) (PAA) in presence of silver nanoparticles to yield (TMC/PAA/Ag)
      nanocomposites with different Ag weight ratios. Structure of TMC, PAA and TMC/PAA
      (PEC) were proved via different analysis tools. TMC/PAA and its Ag nanocomposites
      are used as antimicrobial agents against different pathogenic bacteria and fungi
      to solve microbial pollution. TMC/PAA-Silver nanocomposites had the highest
      antimicrobial activity which increases with increasing Ag %. Cytotoxicity data
      confirmed also that TMC/PAA/Ag (3%) had the most cytotoxic effect (the less cell
      viability %) towards colon cancer. TMC/PAA (PEC) was formed through electrostatic
      interactions between N-quaternized (-N+R3) groups in TMC and carboxylate (-COO-)
      groups in PAA.

PMID- 29339280
TI  - Simultaneous degumming and production of a natural gum from Crotalaria juncea
      seeds: Physicochemical and rheological characterization.
AB  - The oil extracted from Crotalaria juncea (Sunn-hemp) contains 70% of gum. Several
      methods of degumming are attempted in order to maximize the yield of gum. During
      appropriate water induced degumming, about 95-98% of phosphatides are separated.
      The maximum oil yield for two types of degummimg processes are 0.59% and 0.69%
      corresponding to hot water and pure O-phosphoric acid (19.88 N) treatment
      respectively. The % oil yield obtained for TOP degumming is about 0.78%. Physico
      chemical characteristics of the isolated gum such as moisture, ash, protein, fat
      and aqueous solubility along with FTIR and TGA analysis are studied in order to
      evaluate the effect of extraction process. The behaviour of gum on the molecular
      scale is evaluated through alcohol treatment. Chromatographic analysis determines
      the monosaccharide content of the gum with glucose: xylose: arabinose::54: 34:1.
      Rheological characterization shows that the juncea gum solutions are shear rate
      dependent and the behaviour is shear-thinning (or pseudoplastic). Results show
      that the temperature dependent viscosity decreases with increasing shear rate.

PMID- 29339281
TI  - Bifidogenic effects of Cordyceps sinensis fungal exopolysaccharide and konjac
      glucomannan after ultrasound and acid degradation.
AB  - The bifidogenic effects of exopolysaccharide (EPS) of a medicinal fungus
      (Cordyceps sinensis) and a well-known food polysaccharide konjac glucomannan
      (KGM) with different molecular weight (MW) ranges were evaluated through in vitro
      experiments in liquid cultures of Bifidobacteria. Native EPS and KGM were
      partially degraded with power ultrasound (US) to improve the water solubility,
      and further hydrolysed with trifluoroacetic acid to much lower MW. The acid
      hydrolysed fractions (EPS-AH and KGM-AH) supported the growth of all five tested
      bifidobacterial species, while the US-degraded high MW fractions, EPS-US and KGM
      US, could only slightly support the growth of some species. All EPS fractions
      increased the acetic acid production of most bifidobacterial species. Most
      remarkably, the high MW EPS-US, EPS-AH and KGM-US fractions significantly
      enhanced the cell viability with much higher colony forming unit (CFU) counts,
      suggesting a protective effect of these high MW polysaccharides for the bacterial
      survival. The results have shown that MW was a significant factor on the
      bifidogenic properties of partially degraded EPS and KGM.

PMID- 29339282
TI  - Probing the interaction of two chemotherapeutic drugs of oxali-palladium and 5
      fluorouracil simultaneously with milk carrier protein of beta-lactoglobulin.
AB  - beta-Lactoglobulin (betaLG) is a basic element of globular carrier protein, which
      is the major protein in the whey of ruminant milk and is of main interest in the
      dairy industry. In the present study, the simultaneous effects of both of the
      important anticancer drugs of 5-fluorouracil (5-FU) and oxali-palladium, on the
      structure of betaLG were investigated using different spectroscopic methods of
      fluorescence and circular dichroism (CD) in combination with a molecular docking
      at two temperatures of 25 and 37 degrees C. The resulted data from intrinsic
      fluorescence spectra of protein indicated that 5-FU and oxalli-palladium can
      quench the fluorescence intensity of betaLG in dose-dependent manner via static
      mechanism of fluorescence quenching. Analysis of fluorescence quenching data in
      agreement with theoretical results have represented that there are I binding
      sites on betaLG for binding of oxali-palladium and also II binding sites for 5
      FU, at both temperatures of 25 and 37 degrees C. Also, competitive binding
      results showed that the number of binding sites on protein for each of the drug
      when the protein incubated with one of the drug did not show any changes. The
      values of thermodynamic parameters of DeltaH degrees , DeltaS degrees  and DeltaG
      degrees  illustrate that van der Waals and hydrogen-bond interactions have the
      main role in the binding of oxali-palladium and 5-FU to betaLG, respectively. The
      analysis of circular dichroism spectra indicated reduction in stability of the
      protein and alteration in the secondary structure of protein with reduction of
      alpha-helical structure and increasing of beta-sheet structure in the presence of
      increasing concentration of oxali-palladium and 5-FU. Also, the transition
      temperature (Tm) value of betaLG indicated the significant decreasing in the
      presence of 5-FU and oxali-palladium. As a result, it can be concluded that both
      of the chemotherapeutic drugs of oxali-palladium and 5-FU can bind to independent
      binding sites on carrier protein of betaLG, which can be used in design and
      simultaneous delivery of both drugs.

PMID- 29339283
TI  - Hydroxyethyl cellulose hydrogel for wound dressing: Fabrication, characterization
      and in vitro evaluation.
AB  - In this study, new hydrogel membranes were developed based on hydroxyethyl
      cellulose (HEC) supplemented with tungsten oxide for further implementing in
      wound treatment. HEC hydrogel membranes were fabricated and crosslinked using
      citric acid (CA). Various tests were carried out including FTIR, XRD, porosity
      measurements, swelling, mechanical properties, gel fraction, and thermal
      gravimetric analysis to evaluate the efficiency of the prepared membranes as
      wound dressing material. In addition, wound healing activity of the examined
      membranes for human dermal fibroblast cell line was investigated employing in
      vitro scratching model. Furthermore, the potency of the prepared membranes to
      suppress wound complications was studied via determination of their anti
      inflammatory and antibacterial activities exploiting MTT, ELISA, and disk agar
      diffusion methods. The results demonstrated that the HEC hydrogel membranes
      revealed an anti-inflammatory and antibacterial efficacy. Moreover, HEC improved
      the safety of tungsten oxide toward normal human cells (white blood cells and
      dermal fibroblast). Furthermore, HEC membranes loaded with WO3 revealed the
      highest activities against Salmonella sp. pursued by P. aeruginosa in compared
      with the negative HEC hydrogel membrane. The current approach corroborated that
      HEC amended by tungsten oxide could be applied as a promising safe candidate for
      wound dressing material.

PMID- 29339284
TI  - rBmTI-6 attenuates pathophysiological and inflammatory parameters of induced
      emphysema in mice.
AB  - Protease/anti-protease imbalance is the main pathogenic mechanism of emphysema
      and protease inhibitors have been recognized as potential molecules to treat the
      disease conditions. In this work the rBmTI-6 first domain (rBmTI-6-D1), a
      recombinant Kunitz-type serine proteinase inhibitor, was used to verify its
      effect in prevention or minimization of PPE-induced emphysema in mice. C57BL/6
      mice were submitted to a PPE-induced emphysema model and treated with rBmTI-6-D1
      before the emphysema development. We showed that the rBmTI-6-D1 treatment was
      sufficient to avoid the loss of elastic recoil, an effective decrease in alveolar
      enlargement and in the number of macrophages and lymphocytes in bronchoalveolar
      lavage fluid. Proteolytic analysis showed a significant increase in elastase
      activity in PPE-VE (induced emphysema) group that is controlled by rBmTI-6-D1.
      Kallikrein activity was decreased in the PPE-rBmTI6 (induced emphysema and
      inhibitor treated) group when compared to PPE-VE group. Although rBmTI-6-D1, did
      not present a neutrophil elastase (NE) inhibitory activity, the results show that
      the inhibitor interfered in the pathway of NE secretion in PPE-emphysema mice
      model. The role of rBmTI-6-D1 in the prevention of emphysema development in the
      mice model, apparently, is related with a control of inflammatory response due
      the trypsin/kallikrein inhibitory activity of rBmTI-6-D1.

PMID- 29339285
TI  - Facile synthesis and rheological characterization of nanocomposite hyaluronan
      organoclay hydrogels.
AB  - We report a facile methodology for the synthesis of inorganic-organic hydrogels
      based on integrative assembly of aminopropyl magnesium phyllosilicate (aminoclay)
      and sodium salt of hyaluronic acid. The viscoelastic materials produced by
      electrostatic interactions and crosslinking of hyaluronan in the presence of
      exfoliated synthetic organoclay results in the formation of gel-like behavior
      retaining a high amount of water. This was confirmed by a rheological study
      revealing significant dominance of the elastic response over the entire
      deformation frequency range used. The mechanical strength of the aminoclay
      hyaluronan hydrogels was found to be higher than that for related materials based
      on poly(vinylpyrrolidone)-aminoclay hydrogels.

PMID- 29339286
TI  - Chitosan: An undisputed bio-fabrication material for tissue engineering and bio
      sensing applications.
AB  - Biopolymers have been serving the mankind in various ways since long. Over the
      last few years, these polymers have found great demand in various domains which
      includes bio medicine, tissue engineering, bio sensor fabrications etc. because
      of their excellent bio compatibility. In this context, chitosan has found global
      attention due to its environmentally benign nature, biocompatibility,
      biodegradability, and ease of availability. In last one decade or so, extensive
      research in active biomaterials, like chitosan has led to the development of
      novel delivery systems for drugs, genes, and biomolecules; and regenerative
      medicine. Additionally, chitosan has also witnessed its usage in
      functionalization of biocompatible materials, nanoparticle (NP) synthesis, and
      immobilization of various bio-recognition elements (BREs) to form active bio
      surfaces with great ease. Keeping these aspects in mind, we have written a
      comprehensive review which aims to acquaint its readers with the exceptional
      properties of chitosan and its usage in the domain of biomedicine, tissue
      engineering, and biosensor fabrication. Herein, we have briefly explained various
      aspects of direct utilization of chitosan and then presented vivid strategies
      towards formulation of chitosan based nanocomposites for biomedicine, tissue
      engineering, and biosensing applications.

PMID- 29339287
TI  - Scalable fabrication of sulfated silk fibroin nanofibrous membranes for efficient
      lipase adsorption and recovery.
AB  - Fabricating adsorptive materials for fast and high efficient adsorption of
      enzymes is critical to match the great demands for separation and recovery of
      enzymes used as biocatalysts. However, it has proven extremely challenging. Here,
      we report a cost-effective strategy to construct the sulfated group surface
      functionalized silk fibroin nanofibrous membranes (SS-SFNM) under mild conditions
      for positively charged Candida rugosa lipase adsorption. The naturally abundant
      silk is thus reconstructed into nanofibrous membranes with tunable surface
      functions. Thereby, the resultant SS-SFNM exhibited excellent adsorption
      performance towards lipase, including a superior adsorption capacity of 148 mg g
      1, fast adsorption equilibrium within 3 h and good reversibility. The fabrication
      of such fascinating silk-based materials may provide new chance into the design
      and development of multi-functional membranes for various separated applications.

PMID- 29339288
TI  - Hyaluronic acid in Pluronic F-127/F-108 hydrogels for postoperative pain in
      arthroplasties: Influence on physico-chemical properties and structural
      requirements for sustained drug-release.
AB  - In this study, we reported the hyaluronic acid (HA) on supramolecular structure
      of Pluronic F-127 (PLF-127) and/or Pluronic F-108 (PLF-127) hydrogels, as well as
      their effects on release mechanisms, looking forward their application as
      lidocaine (LDC) drug-delivery systems in arthroplastic surgeries. We have studied
      the HA-micelle interaction using Dynamic Light Scattering (DLS), the
      micellization and sol-gel transition processes by Differential Scanning
      Calorimetry (DSC) and Rheology., of PL-based hydrogels and. The presence of HA
      provided the formation of larger micellar dimensions from ~26.0 to 42.4nm. The
      incorporation of HA did not change the micellization temperatures and stabilized
      hydrogels rheological properties (G'>G"), showing no interference on PL
      thermoreversible properties. Small-Angle-X-ray Scattering (SAXS) patterns
      revealed that HA incorporation effects were pronounced for PLF-127 and PLF-108
      systems, showing transitions from lamellar to hexagonal phase organization (HA
      PLF-127) and structural changes from cubic to gyroid and/or cubic to lamellar.
      The HA insertion effects were also observed on drug release profiles, since lower
      LDC release constants (Krel=0.24-0.41mM.h-1) were observed for HA-PLF-127, that
      presented a hexagonal phase organization. Furthermore, the HA-PL systems
      presented reduced in vitro cytotoxic effects, pointed out their tendency to self
      assembly and possible application as drug delivery systems.

PMID- 29339289
TI  - Characterization of two extracellular beta-glucosidases produced from the
      cellulolytic fungus Aspergillus sp. YDJ216 and their potential applications for
      the hydrolysis of flavone glycosides.
AB  - A cellulolytic fungus YDJ216 was isolated from a compost and identified as an
      Aspergillus sp. strain. Two extracellular beta-glucosidases, BGL1 and BGL2, were
      purified using ultrafiltration, ammonium sulfate fractionation, and High-Q
      chromatography. Molecular masses of BGL1 and BGL2 were estimated to be 97 and 45
      kDa, respectively, by SDS-PAGE. The two enzymes eluted as one peak at 87 kDa by
      Sephacryl S-200 chromatography, and located at similar positions in a zymogram
      after intact gel electrophoresis, suggesting BGL1 and BGL2 might be monomeric and
      dimeric, respectively. Both enzymes showed similar enzymatic properties; they
      were optimally active at pH 4.0-4.5 and 60  degrees C, and had similar half-lives
      at 70  degrees C. Two enzymes also preferred p-nitrophenyl glucose (pNPG) with
      the same Km and hardly hydrolyzed cellobiose, suggesting both enzymes are aryl
      beta-glucosidases. However, Vmax for pNPG of BGL1 (953.2 U/mg) was much higher
      than those of BGL2 (66.5U/mg) and other beta-glucosidases reported. When tilianin
      (a flavone glycoside of acacetin) was reacted with both enzymes, inhibitory
      activity for monoamine oxidase, relating to oxidation of neurotransmitter amines,
      was increased closely to the degree obtained by acacetin. These results suggest
      that BGL1 and BGL2 could be used to hydrolyze flavone glycosides to improve their
      inhibitory activities.

PMID- 29339290
TI  - Biocatalytic strategies in the production of galacto-oligosaccharides and its
      global status.
AB  - Galactooligosaccharides (GOSs) are the non-digestible carbohydrates that are
      composed of 3-10 or longer molecules of galactose and the terminal glucose
      molecule. These are considered as prebiotics owing to their various health
      benefits, and therefore is the major focus of research. These are generally
      synthesized by the catalytic activity of the glycoside hydrolases (GH) utilizing
      lactose as a substrate, which results in the mixture of GOSs differing in their
      degree of polymerization. Different microbial glycoside hydrolases have been used
      for the production. Moreover, to improve the production, different
      biotechnological strategies have been applied, such as use of immobilized enzymes
      or recombinant enzymes. Thus, this review discusses the different prospects of
      GOSs production and its purification techniques.

PMID- 29339291
TI  - Social capital and child nutrition in India: The moderating role of development.
AB  - Empirical studies of social capital rarely take into account the socioeconomic
      context of the region in which it operates, indeed as most of this research has
      been located in high income countries. It is imperative to investigate how
      development may influence the impact of social capital, especially in developing
      countries. This paper examines the relationship between social capital and child
      nutrition using the India Human Development Survey, 2005-2006. Using a multilevel
      framework and a sample of 6770 rural children under the age of five, it finds
      that household based bridging social capital, expressed as connections with
      development based organizations, is positively associated with child nutrition.
      Bonding social capital, expressed as ties with caste and religious based
      organizations, has the opposite impact. At the village level, contextual measures
      of social capital are associated with nutritional status of children, but their
      influence is conditional on local development.

PMID- 29339292
TI  - Selective HCN1 block as a strategy to control oxaliplatin-induced neuropathy.
AB  - Chemotherapy-Induced Peripheral Neuropathy (CIPN) is the most frequent adverse
      effect of pharmacological cancer treatments. The occurrence of neuropathy
      prevents the administration of fully-effective drug regimen, affects negatively
      the quality of life of patients, and may lead to therapy discontinuation. CIPN is
      currently treated with anticonvulsants, antidepressants, opioids and non-opioid
      analgesics, all of which are flawed by insufficient anti-hyperalgesic efficacy or
      addictive potential. Understandably, developing new drugs targeting CIPN-specific
      pathogenic mechanisms would dramatically improve efficacy and tolerability of
      anti-neuropathic therapies. Neuropathies are associated to aberrant excitability
      of DRG neurons due to the alteration in the expression or function of a variety
      of ion channels. In this regard, Hyperpolarization-activated Cyclic Nucleotide
      gated (HCN) channels are overexpressed in inflammatory and neuropathic pain
      states, and HCN blockers have been shown to reduce neuronal excitability and to
      ameliorate painful states in animal models. However, HCN channels are critical in
      cardiac action potential, and HCN blockers used so far in pre-clinical models do
      not discriminate between cardiac and non-cardiac HCN isoforms. In this work, we
      show an HCN current gain of function in DRG neurons from oxaliplatin-treated
      rats. Biochemically, we observed a downregulation of HCN2 expression and an
      upregulation of the HCN regulatory beta-subunit MirP1. Finally, we report the
      efficacy of the selective HCN1 inhibitor MEL57A in reducing hyperalgesia and
      allodynia in oxaliplatin-treated rats without cardiac effects. In conclusion,
      this study strengthens the evidence for a disease-specific role of HCN1 in CIPN,
      and proposes HCN1-selective inhibitors as new-generation pain medications with
      the desired efficacy and safety profile.

PMID- 29339293
TI  - Methylphenidate significantly alters the functional coupling between the
      prefrontal cortex and dopamine neurons in the ventral tegmental area.
AB  - Amphetamine-like psychostimulants, including methylphenidate, have been shown to
      produce two opposing effects on dopamine (DA) neurons: a DA receptor-mediated
      feedback inhibition and a non-DA receptor-mediated excitation. To test whether
      the latter effect is mediated through the prefrontal cortex (PFC), we made dual
      site recordings from the PFC and ventral tegmental area (VTA). Consistent with
      previous reports, methylphenidate inhibited VTA DA neurons. The D2 receptor
      antagonist raclopride completely reversed the inhibition and further increased
      the activity, particularly bursting, to above pre-drug baseline. This increase in
      DA cell activity was blocked by the alpha1 receptor antagonist prazosin,
      suggesting an effect mediated through alpha1 receptors. Recordings in the PFC
      showed that methylphenidate increased PFC UP state duration and shifted the
      functional coupling between the PFC and DA neurons from negative to positive. The
      former effect was partially reversed by not only prazosin, but also raclopride,
      whereas the latter was reversed only by raclopride. These results suggest that
      methylphenidate increases PFC cell activity through both alpha1 and D2 receptors.
      Its effect on PFC-DA cell functional coupling, however, is mediated through D2
      receptors. The finding that the latter effect was unaffected by prazosin further
      suggests that it does not play a significant role in the alpha1-mediated
      excitatory effect of methylphenidate on DA neurons. However, the shift in PFC-DA
      cell functional coupling from negative to positive may significantly alter the
      relative timing between DA and glutamate release from DA and PFC terminals and
      thus the synaptic plasticity that depends on DA-glutamate interaction.

PMID- 29339294
TI  - Ketamine for the treatment of addiction: Evidence and potential mechanisms.
AB  - Ketamine is a dissociative anaesthetic drug which acts on the central nervous
      system chiefly through antagonism of the n-methyl-d-aspartate (NMDA) receptor.
      Recently, ketamine has attracted attention as a rapid-acting anti-depressant but
      other studies have also reported its efficacy in reducing problematic alcohol and
      drug use. This review explores the preclinical and clinical research into
      ketamine's ability to treat addiction. Despite methodological limitations and the
      relative infancy of the field, results thus far are promising. Ketamine has been
      shown to effectively prolong abstinence from alcohol and heroin in detoxified
      alcoholics and heroin dependent individuals, respectively. Moreover, ketamine
      reduced craving for and self-administration of cocaine in non-treatment seeking
      cocaine users. However, further randomised controlled trials are urgently needed
      to confirm ketamine's efficacy. Possible mechanisms by which ketamine may work
      within addiction include: enhancement of neuroplasticity and neurogenesis,
      disruption of relevant functional neural networks, treating depressive symptoms,
      blocking reconsolidation of drug-related memories, provoking mystical experiences
      and enhancing psychological therapy efficacy. Identifying the mechanisms by which
      ketamine exerts its therapeutic effects in addiction, from the many possible
      candidates, is crucial for advancing this treatment and may have broader
      implications understanding other psychedelic therapies. In conclusion, ketamine
      shows great promise as a treatment for various addictions, but well-controlled
      research is urgently needed. This article is part of the Special Issue entitled
      'Psychedelics: New Doors, Altered Perceptions'.

PMID- 29339295
TI  - Characteristics of clinical and environmental vanM-carrying vancomycin-resistant
      enterococci isolates from an infected patient.
AB  - vanM, an uncommon glycopeptide resistance gene, was first identified in an
      Enterococcus faecium isolate (Efm-HS0661) from Shanghai, China, in 2006 and has
      been predominant in this city since 2011. A vanM-carrying E. faecium was isolated
      from the bloodstream of a patient in an intensive care unit (ICU) in Hangzhou,
      China, in 2014. Further surveillance screening of a rectal swab and environmental
      surfaces of the patient yielded a large number of vanM-positive E. faecium. These
      isolates (including 1 from the bloodstream, 1 from the rectal swab and 43
      representative isolates from environmental samples) were classified into four
      pulsed-field gel electrophoresis (PFGE) patterns and two sequence types (ST78 and
      ST564). PCR amplification and sequence analysis indicated that the genetic
      structure surrounding the vanM gene of these isolates was similar to that of the
      original vanM-carrying isolate Efm-HS0661. This study highlights the emergence of
      infections and environmental contamination caused by vanM-carrying E. faecium in
      an ICU of another Chinese city outside of Shanghai.

PMID- 29339296
TI  - Silent transmission of an IS1294b-deactivated mcr-1 gene with inducible colistin
      resistance.
AB  - Global dissemination of the mobile colistin resistance mcr-1 is of particular
      concern as colistin is one of the last-resort antibiotics for the treatment of
      severe infections caused by carbapenem-resistant Gram-negative bacteria. In this
      study, an inactive form of mcr-1 in a fluoroquinolone-resistant and colistin
      susceptible uropathogenic Escherichia coli isolate (ECO3347) was characterised.
      The mcr-1 gene was deactivated by insertion of a 1.7-kb IS1294b element flanked
      by two tetramers (GTTC) and located on a 62-kb pHNSHP45-like plasmid (p3347-mcr
      1). Single-step and multistep selections were used to induce colistin resistance
      in vitro in ECO3347. ECO3347 acquired colistin resistance (MIC = 16-32 mg/L) only
      after a serial passage selection with increasing concentrations of colistin (2-8
      mg/L). Deactivated mcr-1 was re-activated by loss of IS1294b without any remnants
      in most colistin-resistant mutants. In addition, a novel amino acid variant
      (Leu105Pro) in the CheY homologous receiver domain of PmrA was detected in one
      colistin-resistant mutant. Plasmid p3347-mcr-1+ carrying the re-activated mcr-1
      gene is transferrable to E. coli J53 recipient with a high conjugation rate (ca.
      10-1 cells per recipient cell). Transconjugants showed an identical growth status
      to J53, suggesting lack of a fitness cost after acquiring p3347-mcr-1+. These
      results highlight that the disrupted mcr-1 gene has the potential for wide silent
      dissemination with the help of pHNSHP45-like epidemic plasmids. Inducible
      colistin resistance may likely compromise the success of clinical treatment and
      infection control. Continuous monitoring of mcr-1 is imperative for understanding
      and tackling its dissemination in different forms.

PMID- 29339297
TI  - Experiences and perspectives of implementing antimicrobial stewardship in five
      French hospitals: a qualitative study.
AB  - The aim of this study was to describe current antimicrobial stewardship
      programmes (ASPs) in France, both at policy level and at local implementation
      level, and to assess how ASP leaders (ASPL) worked and prioritised their
      activities. A qualitative study based on face-to-face semi-structured interviews
      with healthcare professionals responsible for ASPs across five French hospitals
      was conducted. Five infectious diseases specialists and one microbiologist were
      interviewed between April-June 2016. Stewards had dedicated time to perform ASP
      activities in two university-affiliated hospitals, whilst in the other hospitals
      (one university, one general and one semi-private), ASPLs had to balance these
      activities with clinical practice. Consequently, they had to adapt interventions
      according to their resources (IT or human). Responding to colleagues'
      consultation requests formed baseline work. Systematic and pro-active measures
      allowed for provision of unsolicited counselling, whilst direct counselling on
      wards required appropriate staffing. ASPLs aimed at increasing clinicians'
      ability to prescribe adequately and awareness of the unintended consequences of
      inappropriate use of antibiotics. Thus, persuasive, e.g. education, measures were
      preferred to coercive ones. ASPLs faced several challenges in implementing the
      ASP: overcoming physicians' or units' reluctance; and balancing the influence of
      medical hierarchy and professional boundaries. Beyond resources constraints,
      ASPLs' conceptions of their work, as well as contextual and cultural aspects, led
      them to adopt a persuasive and collaborative approach of counselling. This is the
      first qualitative study regarding ASPs in France exploring stewards' experiences
      and points of view.

PMID- 29339298
TI  - Implementation and impact of an audit and feedback antimicrobial stewardship
      intervention in the orthopaedics department of a tertiary-care hospital: a
      controlled interrupted time series study.
AB  - A prospective audit and feedback antimicrobial stewardship intervention conducted
      in the Orthopaedics Department of a university hospital in Portugal was evaluated
      by comparing an interrupted time series in the intervention group with a non
      intervention (control) group. Monthly antibiotic use (except cefazolin) was
      measured as the World Health Organization's Anatomical Therapeutic Chemical
      defined daily doses (ATC-DDD) from January 2012 to September 2016, excluding the
      6-month phase of intervention implementation starting on 1 January 2015. Compared
      with the control group, the intervention group had a monthly decrease in the use
      of fluoroquinolones by 2.3 DDD/1000 patient-days [95% confidence interval (CI) 
      3.97 to -0.63]. An increase in the use of penicillins by 103.3 DDD/1000 patient
      days (95% CI 47.42 to 159.10) was associated with intervention implementation,
      followed by a decrease during the intervention period (slope = -5.2, 95% CI -8.56
      to -1.82). In the challenging scenario of treatment of osteoarticular and
      prosthetic joint infections, an audit and feedback intervention reduced
      antibiotic exposure and spectrum.

PMID- 29339299
TI  - Is There a Difference in the Outcome of Mid-Urethral Sling Operations Performed
      by Urogynecologists Compared with Supervised Residents?
AB  - STUDY OBJECTIVE: To compare the operative results of midurethral sling (MUS)
      surgeries for stress urinary incontinence (SUI) performed by residents under the
      guidance of an attending specialist in urogynecology and those performed by
      attendings. DESIGN: Retrospective chart review (Canadian Task Force
      classification II-2). SETTING: University hospital. PATIENTS: A retrospective
      analysis of all MUS surgeries performed at a single public tertiary medical
      center between January 2009 and December 2013 was carried out. A total of 257
      patients underwent transobturator tape (TOT) placement during the study period,
      including 136 (52.9%) placed by an attending specialist in urogynecology (group
      A) and 121 (47.1%) placed by a resident, under the guidance of an attending
      (group B). MEASUREMENTS: The efficacy of treatment was evaluated in terms of
      early postoperative course, reoperation, and symptom improvement, as based on the
      Pelvic Floor Distress Inventory short form (PFDI-20) questionnaire. The primary
      outcome was patient-reported symptoms of SUI, as assessed with the PFDI-20
      questionnaire, as well as absence of surgical retreatment for SUI. RESULTS:
      Immediate postoperative complications were comparable in the 2 groups, as were
      subjective failure and self-reported SUI. The primary outcome-moderate and severe
      symptoms of SUI-were reported by 23.7% of the patients in group A and 23.6% of
      those in group B (p = .91). At a mean follow-up of 40 months in both groups,
      symptoms, as assessed using the urinary scale and prolapse scale of the PFDI-20,
      were also similar in the 2 groups. The rate of reoperation with repeated sling
      for SUI was 5% in both groups. CONCLUSION: The operative results of TOT surgery
      for SUI performed by residents under the guidance of an attending specialist in
      urogynecology did not differ significantly from those performed by the attendings
      themselves.

PMID- 29339300
TI  - Robotic Surgery in Elderly and Very Elderly Gynecologic Cancer Patients.
AB  - STUDY OBJECTIVE: To investigate the feasibility, safety, and short-term outcomes
      of robotic surgery (RS) for gynecologic oncologic indications (cervical,
      endometrial, and ovarian cancer) in elderly patients, especially women age 65 to
      74 years (elderly group [EG]) compared with women age >=75 years (very elderly
      group [VEG]). DESIGN: Retrospective cohort study (Canadian Task Force
      classification II-2). SETTING: Catholic University of the Sacred Heart, Rome,
      Italy. PATIENTS: Between May 2013 and April 2017, 204 elderly and very elderly
      patients underwent RS procedures for gynecologic malignancies. RESULTS: The
      median age was 71 years (range, 65-74 years) in the EG and 77 years (range, 75-87
      years) in the VEG. The incidence of cardiovascular disease was higher in the VEG
      (p = .038). The EG and VEG were comparable in terms of operative time, blood
      loss, and need for blood transfusion. Almost all (98.5%) of the patients
      underwent total/radical hysterectomy, 109 patients (55.6% of the EG vs 48.3% of
      the VEG) underwent pelvic lymphadenectomy, and 19 patients (10.5% of the EG vs
      6.7% of the VEG) underwent aortic lymphadenectomy. A total of 7 (3.4%)
      conversions to open surgery were registered. Only 3 patients required
      postoperative intensive care unit admission. The median length of hospital stay
      was 2 days in each group. A total of 11 patients (5.6%) had early postoperative
      complications. Four patients (2.8%) in the EG and 2 patients (3.3%) in the VEG
      experienced grade >=2 complications. At the time of analysis, median follow-up
      was 18 months (range, 6-55 months). Eleven patients (5.6%) experienced disease
      relapse, 2 (1%) died of disease, and 3 (1.5%) died of cardiovascular disease.
      CONCLUSIONS: This study demonstrates the feasibility, safety, and good short-term
      outcomes of RS in elderly and very elderly gynecologic cancer patients. No
      patient can be considered too old for a minimally invasive robotic approach, but
      a multidisciplinary approach is the best management pathway; efforts to reduce
      associated morbidity are essential.

PMID- 29339301
TI  - A Polypectomy Nearly Becoming a Tragedy: A Case of Multiorgan Perforation.

PMID- 29339302
TI  - Bilateral Ureteral Stent Removal after 15 Years: A Case Report.
AB  - We present the first reported case of a patient with a forgotten ureteral stent.
      A 68-year-old woman had undergone radical hysterectomy for cervical cancer in
      1997, at which time bilateral ureteral stents were placed. She was admitted to
      our hospital with stranguria, dysuria, and lower back pain of 10 days duration.
      Preoperative radiologic evaluation revealed the presence of ureteral stents,
      which had been in place since 1997. With the patient under general anesthesia,
      the bilateral stents were removed by urethral cystoscopy. No stone formation was
      noted. The procedure was easy and fast, and no intraoperative complications
      occurred.

PMID- 29339303
TI  - Estrogenic activity of cylindrospermopsin and anatoxin-a and their oxidative
      products by FeIII-B*/H2O2.
AB  - The cyanotoxins released into waters during cyanobacterial blooms can pose
      serious hazards to humans and animals. Apart from their toxicological mechanisms,
      cyanotoxins have been shown to be involved in estrogenic activity by in vivo and
      in vitro assays; however, there is limited information on the change in
      estrogenicity of cyanotoxins following chemical oxidation. In this study, the
      estrogenic activity of cylindrospermopsin (CYL) and anatoxin-a (ANA) at
      concentrations ranging from 2.4 * 10-7 M to 2.4 * 10-12 M (CYL) and 7.1 * 10-6 M
      to 7.1 * 10-11 M (ANA), and after treatment by the FeIII-B*/H2O2 catalyst system,
      was investigated by the yeast estrogen screen (YES) assay. The results indicate
      that CYL and ANA acted as agonists in the YES assay (CYL logEC50 = -8.901; ANA
      logEC50 = -6.789), their binding affinity to estrogen receptors is associated
      with their intrinsic properties, including ring structures and toxicant
      properties. CYL and ANA were shown to simulate endocrine disrupting chemicals
      (EDCs) to modulate the 17beta-estradiol-induced estrogenic activity, resulting in
      non-monotonic dose responses. The treated CYL showed a significantly altered
      estrogenicity compared to the untreated CYL (T(2) = 8.168, p <= .05), while the
      estrogenicity of the treated ANA was not significantly different to the untreated
      ANA (T(2) = 1.295, p > .05). Intermediate products generated from CYL and ANA
      oxidized by FeIII-B*/H2O2 were identified using Q-Exactive Tandem Mass
      Spectrometry (LC-MS/MS). Treatment with FeIII-B*/H2O2 yielded open-ring by
      products which likely resulted in CYL's reduced binding affinity to estrogen
      receptors. The insignificant change in the estrogenicity of treated ANA was
      possibly a result of its multiple ring structure products, which were likely able
      to bind to estrogen receptors. The comparisons for the estrogenicity of these
      cyanotoxins before and after FeIII-B*/H2O2 treatment suggest that the reductions
      in estrogenicity achieved by oxidation were dependent on the levels of
      cyanotoxins removed, as well as the estrogenicity of the degradation products.
      This is the first study on the change in the estrogenicity of CYL and ANA upon
      oxidation by FeIII-B*/H2O2, a high activity catalyst system.

PMID- 29339304
TI  - Transformation products formation of ciprofloxacin in UVA/LED and UVA/LED/TiO2
      systems: Impact of natural organic matter characteristics.
AB  - The role of natural organic matter (NOM) in contaminants removal by photolysis
      and photocatalysis has aroused increasing interest. However, evaluation of the
      influence of NOM characteristics on the transformation products (TPs) formation
      and transformation pathways of contaminants has rarely been performed. This study
      investigated the decomposition kinetics, mineralization, TPs formation and
      transformation pathways of antibiotic ciprofloxacin (CIP) during photolysis and
      photocatalysis in the presence of three commercial NOM isolates (Sigma-Aldrich
      humic acid (SAHA), Suwannee River humic acid (SRHA) and Suwannee River NOM
      (SRNOM)) by using UVA light emitting diode (UVA/LED) as an alternative light
      source. NOM isolates insignificantly affected CIP photolysis but strongly
      inhibited CIP photocatalysis due to competitive radical quenching. The inhibitory
      effect followed the order of SAHA (49.6%) > SRHA (29.9%) > SRNOM (21.2%),
      consistent with their *OH quenching abilities, SUVA254 values and orders of
      aromaticity. Mineralization rates as revealed by F- release were negatively
      affected by NOM during CIP photocatalysis. TPs arising from hydroxylation and
      defluorination were generally suppressed by NOM isolates in UVA/LED and
      UVA/LED/TiO2 systems. In contrast, dealkylation and oxidation of piperazine ring
      were promoted by NOM. The enhancement in the apparent formation kinetics (kapp)
      of TP245, TP291, TP334a, TP334b and TP362 followed the order of SRNOM > SRHA >
      SAHA. kapp values were positively correlated with O/C ratio, carboxyl content,
      E2/E3 and fluorescence index (FI) of NOM and negatively related with SUVA254
      values. The observed correlations indicate that NOM properties are important in
      determining the fate and transformation of organic contaminants during photolysis
      and photocatalysis.

PMID- 29339305
TI  - Modelling ROS formation in boreal lakes from interactions between dissolved
      organic matter and absorbed solar photon flux.
AB  - Concentrations of dissolved organic matter (DOM) are increasing in a large number
      of lakes across the Northern hemisphere. This browning serves a dual role for
      biota by protecting against harmful ultraviolet radiation, while also absorbing
      photosynthetically active radiation. The photochemical activation of DOM and
      subsequent formation of reactive oxygen species (ROS) is a potentially harmful
      side effect, but can be difficult to measure directly in situ. In this study, we
      combine a data set of physico-chemical properties from 71 Nordic lakes with in
      vitro ROS formation quantum yields to predict ROS formations across a
      representative boreal ecosystem gradient. For the upper centimeter of the water
      column, we calculate ROS formations in the range of 7.93-12.56 MUmol L-1 h-1. In
      the first meter, they range between 1.69 and 6.69 MUmol L-1 h-1 and in the
      remaining depth the range is 0.01-0.46 MUmol L-1 h-1. These ROS formations are
      comparable with previously field-measured hydrogen peroxide formation rates and
      likely affect both phyto- and zooplankton, as well as lake chemistry.
      Interestingly, wavelengths of the visible spectrum (>400 nm) contribute more than
      half of the overall ROS formation in surface-near water layers. The association
      between DOM and ROS formation was found to be two-fold. While DOM promotes ROS
      formation in the first centimeters of the water column, the shading effect of
      light attenuation overpowers this with increasing depth. In the context of water
      browning, our results indicate the emergence of an underestimated oxidative
      stress environment for lake biota in the upper centimeters of the water column.

PMID- 29339306
TI  - Morphological changes of bacterial cells upon exposure of silver-silver chloride
      nanoparticles synthesized using Agrimonia pilosa.
AB  - Facile, eco-friendly synthesis of metal nanoparticles has been proposed as a cost
      effective method. In the present study, we propose the facile synthesis of silver
      silver chloride (Ag-AgCl) nanoparticles (NPs) using the medicinally important
      Agrimonia pilosa plant extract without addition of capping or stabilizing agents.
      The Ag-AgCl NPs synthesis was observed at 40  degrees C after 10 min incubation;
      the synthesis of Ag-AgCl NPs was indicated by color change and confirmed by UV
      vis spectroscopic peak at 454 nm. TEM analysis confirmed Ag-AgCl NPs were 10-20
      nm in size and spherical, and oval in shape. Elemental composition was determined
      by energy dispersive X-ray analysis, and crystalline structure was confirmed by X
      ray diffraction spectroscopy. Different phytocomponents present in the plant
      extract were analyzed by Gas Chromatography-Mass spectrometry, and the
      interaction of biomolecules in reduction process was analyzed by Fourier
      transform infrared spectroscopy studies. The synthesized Ag-AgCl NPs showed
      significant antibacterial efficiency, analyzed by well diffusion assay against
      pathogenic bacteria including Bacillus cereus, Listeria monocytogenes,
      Staphylococcus aureus, Staphylococcus saprophyticus, Escherichia coli,
      Pseudomonas putida. Minimum inhibitory concentration and minimum bactericidal
      concentration were evaluated by microbroth dilution, and spread plate method,
      respectively. The possible mechanism of bacterial growth inhibition is due to
      changes in bacterial cell wall morphology that was studied by FE-SEM analysis.

PMID- 29339307
TI  - Anticoccidial activity of fruit peel of Punica granatum L.
AB  - In the interests of food safety and public health, plants and their compounds are
      now re-emerging as an alternative approach to treat parasitic diseases. Here, we
      studied the anticoccidial effect of different solvent extracts of the fruit peel
      of Punica granatum-a commercial waste from pomegranate juice industries. The hope
      underlying these experiments was to find a sustainable natural product for
      controlling coccidiosis. The plant extracts were prepared using solvents of
      different polarity. Acute oral toxicity study was first carried out to see the
      safety of crude extracts. A high dose of crude extracts (300 mg/kg body weight)
      was tested for possession of anticoccidial activity against experimentally
      induced coccidial infection in broiler chicken. Activity was measured in
      comparison to the reference drug amprolium on the basis of oocyst output
      reduction, mean weight gain of birds and feed conversion ratio. Oocyst output was
      measured using Mc-Masters counting technique. Acute oral toxicity study showed
      that crude extracts of P. granatum are safe up to dosage of 2000 mg/kg body
      weight. LD50 was not determined as mortalities were not recorded in any of the
      five groups of chicken. For anticoccidial activity crude methanolic extract (CME)
      of the fruit peel of P. granatum showed the maximum effect as evident by oocyst
      output reduction (92.8 +/- 15.3), weight gain of birds (1403.0 +/- 11.9 g) and
      feed conversion ratio (1.66 +/- 0.04), thereby affirming the presence of alcohol
      soluble active ingredients in the plant. We also tested different doses (100-400
      mg/kg body weight) of the CME of the fruit peel of P. granatum, the most active
      extract on E. tenella and observed a dose dependent effect. From the present
      study it can be concluded that alcoholic extract of the fruit peel of P. granatum
      has significant potential to contribute to the control of coccidian parasites of
      chicken.

PMID- 29339308
TI  - Antibiotic resistance and virulence traits of bacterial pathogens from infected
      freshwater fish, Labeo rohita.
AB  - Bacterial infectious diseases are a main dangerous problem in Aquaculture
      farming. It causes multiple diseases in fish as well as in human being and it has
      considerable virulence potential. In this connection, the moot of study focus to
      discriminate bacterial isolates recovered from naturally diseased Labeo rohita
      fish and their virulent characteristics. Based on the beta-haemolysis factor,
      four isolates (KADR11, KADR12, KADR13 and KADR14) were selected for further
      delineation. These bacterial isolates showed high similarity with Providencia
      rettgeri, Aeromonas sp., Aeromonas sp. and Aeromonas enteropelogenes
      respectively, using partial 16S r-RNA gene amplification and biochemical
      characterizations were also supported. The further study investigates the
      virulence characteristics of isolates showed separation of outer membrane
      proteins (OMPs) and lipopolysaccharides (LPS) which appeared between 19_80 kDa
      and 20_100 kDa in SDS_PAGE analysis respectively. All the four strains were
      complete resistant (100%) to beta-lactam antibiotics. L. rohita were injected
      intraperitoneally with 0 (control), 2.0 * 104, 2.0 * 105, 2.0 * 106, 2.0 * 107
      and 2.0 * 108 cells/fish of Providencia rettgeri KADR11, Aeromonas sp. KADR12,
      Aeromonas sp. KADR13 and Aeromonas enteropelogenes KADR14 for the determination
      of lethal dose 50 (LD50) values, which were 2.4 * 107, 4.1 * 105, 2.7 * 107 and
      7.4 * 105 cells/fish respectively. The results indicated that isolated strains
      were possessed the high pathogenic potential for L. rohita.

PMID- 29339309
TI  - Late chronotype is associated with enhanced amygdala reactivity and reduced
      fronto-limbic functional connectivity to fearful versus happy facial expressions.
AB  - Increasing evidence suggests late chronotype individuals are at increased risk of
      developing depression. However, the underlying neural mechanisms that confer risk
      are not fully understood. Here, fifty healthy, right-handed individuals without a
      current or previous diagnosis of depression, family history of depression or
      sleep disorder underwent functional magnetic resonance imaging (FMRI).
      Participants completed an implicit emotion processing task (gender
      discrimination) including happy and fearful facial expressions. Linear effects of
      chronotype on BOLD response in bilateral amygdala were tested for significance
      using nonparametric permutation tests. Functional connectivity between amygdala
      and prefrontal cortex was also investigated using psychophysiological interaction
      (PPI) analysis. A significant negative correlation between BOLD response and
      chronotype was observed in bilateral amygdala where later chronotype was
      associated with an enhanced amygdala response to fearful vs. happy faces. This
      response remained significant after sleep quality, age, gender, mood, and time of
      scan were included as covariates in the regression model. Later chronotype was
      also significantly associated with reduced functional connectivity between
      amygdala and dorsal anterior cingulate cortex (dACC). The current results appear
      consistent with theories of impaired emotion regulation of the limbic system
      (particularly the amygdala) associated with depression and may, in part, explain
      the increased vulnerability for depression in late chronotype individuals.

PMID- 29339310
TI  - Distant from input: Evidence of regions within the default mode network
      supporting perceptually-decoupled and conceptually-guided cognition.
AB  - The default mode network supports a variety of mental operations such as semantic
      processing, episodic memory retrieval, mental time travel and mind-wandering, yet
      the commonalities between these functions remains unclear. One possibility is
      that this system supports cognition that is independent of the immediate
      environment; alternatively or additionally, it might support higher-order
      conceptual representations that draw together multiple features. We tested these
      accounts using a novel paradigm that separately manipulated the availability of
      perceptual information to guide decision-making and the representational
      complexity of this information. Using task based imaging we established regions
      that respond when cognition combines both stimulus independence with multi-modal
      information. These included left and right angular gyri and the left middle
      temporal gyrus. Although these sites were within the default mode network, they
      showed a stronger response to demanding memory judgements than to an easier
      perceptual task, contrary to the view that they support automatic aspects of
      cognition. In a subsequent analysis, we showed that these regions were located at
      the extreme end of a macroscale gradient, which describes gradual transitions
      from sensorimotor to transmodal cortex. This shift in the focus of neural
      activity towards transmodal, default mode, regions might reflect a process of
      where the functional distance from specific sensory enables conceptually rich and
      detailed cognitive states to be generated in the absence of input.

PMID- 29339312
TI  - Studying emotion theories through connectivity analysis: Evidence from
      generalized psychophysiological interactions and graph theory.
AB  - Psychological construction models of emotion state that emotions are variable
      concepts constructed by fundamental psychological processes, whereas according to
      basic emotion theory, emotions cannot be divided into more fundamental units and
      each basic emotion is represented by a unique and innate neural circuitry. In a
      previous study, we found evidence for the psychological construction account by
      showing that several brain regions were commonly activated when perceiving
      different emotions (i.e. a general emotion network). Moreover, this set of brain
      regions included areas associated with core affect, conceptualization and
      executive control, as predicted by psychological construction models. Here we
      investigate directed functional brain connectivity in the same dataset to address
      two questions: 1) is there a common pathway within the general emotion network
      for the perception of different emotions and 2) if so, does this common pathway
      contain information to distinguish between different emotions? We used
      generalized psychophysiological interactions and information flow indices to
      examine the connectivity within the general emotion network. The results revealed
      a general emotion pathway that connects neural nodes involved in core affect,
      conceptualization, language and executive control. Perception of different
      emotions could not be accurately classified based on the connectivity patterns
      from the nodes of the general emotion pathway. Successful classification was
      achieved when connections outside the general emotion pathway were included. We
      propose that the general emotion pathway functions as a common pathway within the
      general emotion network and is involved in shared basic psychological processes
      across emotions. However, additional connections within the general emotion
      network are required to classify different emotions, consistent with a
      constructionist account.

PMID- 29339311
TI  - General, crystallized and fluid intelligence are not associated with functional
      global network efficiency: A replication study with the human connectome project
      1200 data set.
AB  - One hallmark example of a link between global topological network properties of
      complex functional brain connectivity and cognitive performance is the finding
      that general intelligence may depend on the efficiency of the brain's intrinsic
      functional network architecture. However, although this association has been
      featured prominently over the course of the last decade, the empirical basis for
      this broad association of general intelligence and global functional network
      efficiency is quite limited. In the current study, we set out to replicate the
      previously reported association between general intelligence and global
      functional network efficiency using the large sample size and high quality data
      of the Human Connectome Project, and extended the original study by testing for
      separate association of crystallized and fluid intelligence with global
      efficiency, characteristic path length, and global clustering coefficient. We
      were unable to provide evidence for the proposed association between general
      intelligence and functional brain network efficiency, as was demonstrated by van
      den Heuvel et al. (2009), or for any other association with the global network
      measures employed. More specifically, across multiple network definition schemes,
      ranging from voxel-level networks to networks of only 100 nodes, no robust
      associations and only very weak non-significant effects with a maximal R2 of 0.01
      could be observed. Notably, the strongest (non-significant) effects were observed
      in voxel-level networks. We discuss the possibility that the low power of
      previous studies and publication bias may have led to false positive results
      fostering the widely accepted notion of general intelligence being associated to
      functional global network efficiency.

PMID- 29339313
TI  - The human body odor compound androstadienone increases neural conflict coupled to
      higher behavioral costs during an emotional Stroop task.
AB  - The androgen derivative androstadienone (AND) is a substance found in human sweat
      and thus may act as human chemosignal. With the current experiment, we aimed to
      explore in which way AND affects interference processing during an emotional
      Stroop task which used human faces as target and emotional words as distractor
      stimuli. This was complemented by functional magnetic resonance imaging (fMRI) to
      unravel the neural mechanism of AND-action. Based on previous accounts we
      expected AND to increase neural activation in areas commonly implicated in
      evaluation of emotional face processing and to change neural activation in brain
      regions linked to interference processing. For this aim, a total of 80 healthy
      individuals (oral contraceptive users, luteal women, men) were tested twice on
      two consecutive days with an emotional Stroop task using fMRI. Our results
      suggest that AND increases interference processing in brain areas that are
      heavily recruited during emotional conflict. At the same time, correlation
      analyses revealed that this neural interference processing was paralleled by
      higher behavioral costs (response times) with higher interference related brain
      activation under AND. Furthermore, AND elicited higher activation in regions
      implicated in emotional face processing including right fusiform gyrus, inferior
      frontal gyrus and dorsomedial cortex. In this connection, neural activation was
      not coupled to behavioral outcome. Furthermore, despite previous accounts of
      increased hypothalamic activation under AND, we were not able to replicate this
      finding and discuss possible reasons for this discrepancy. To conclude, AND
      increased interference processing in regions heavily recruited during emotional
      conflict which was coupled to higher costs in resolving emotional conflicts with
      stronger interference-related brain activation under AND. At the moment it
      remains unclear whether these effects are due to changes in conflict detection or
      resolution. However, evidence most consistently suggests that AND does not draw
      attention to the most potent socio-emotional information (human faces) but rather
      highlights representations of emotional words.

PMID- 29339314
TI  - Surface-based characteristics of the cerebellar cortex visualized with ultra-high
      field MRI.
AB  - Although having a relatively homogeneous cytoarchitectonic organization, the
      cerebellar cortex is a heterogeneous region characterized by different amounts of
      myelin, iron and protein expression profiles. In this study, we used quantitative
      T1 and T2* mapping at ultra-high field (7T) MRI to investigate the tissue
      characteristics of the cerebellar gray matter surface and its layers. Detailed
      subject-specific surfaces were generated at three different cortical depths and
      averaged across subjects to create averaged T1- and T2*-maps on the cerebellar
      surface. T1 surfaces showed an alternation of lower and higher T1 values when
      going from the median to the lateral part of the cerebellar hemispheres. In
      addition, longer T1 values were observed in the more superficial gray matter
      layers. T2*-maps showed a similar longitudinal pattern, but no change related to
      the cortical depths. These patterns are possibly due to variations in the level
      of myelination, iron and zebrin protein expression.

PMID- 29339315
TI  - Insulin sensitivity predicts brain network connectivity following a meal.
AB  - There is converging evidence that insulin plays a role in food-reward signaling
      in the brain and has effects on enhancing cognition. Little is known about how
      these effects are altered in individuals with insulin resistance. The present
      study was designed to identify the relationships between insulin resistance and
      functional brain connectivity following a meal. Eighteen healthy adults (7 male,
      11 female, age: 41-57 years-old) completed a frequently-sampled intravenous
      glucose tolerance test to quantify insulin resistance. On separate days at least
      one week apart, a resting state functional magnetic resonance imaging scan was
      performed: once after a mixed-meal and once after a 12-h fast. Seed-based resting
      state connectivity of the caudate nucleus and eigenvector centrality were used to
      identify relationships between insulin resistance and functional brain
      connectivity. Individuals with greater insulin resistance displayed stronger
      connectivity within reward networks following a meal suggesting insulin was less
      able to suppress reward. Insulin resistance was negatively associated with
      eigenvector centrality in the dorsal anterior cingulate cortex following a meal.
      These data suggest that individuals with less sensitivity to insulin may fail to
      shift brain networks away from reward and toward cognitive control following a
      meal. This altered feedback loop could promote overeating and obesity.

PMID- 29339316
TI  - Diagnosis and management of neuromyelitis optica spectrum disorders - An update.
AB  - Neuromyelitis optica (NMO) and Neuromyelitis optica spectrum disorders (NMOSD)
      are a group of autoimmune conditions characterized by inflammatory involvement of
      the optic nerve, spinal cord and central nervous system. Novel evidence showed a
      key role of autoantibodies against aquaporin-4 immunoglobulin G (AQP4 IgG) in the
      pathogenesis of NMOSD and, recently, new classification and diagnostic criteria
      have been adopted to facilitate an earlier identification and improve the
      management of these conditions. Diagnosis of NMOSD is currently based on
      clinical, neuroimaging and laboratory features. Standard treatment is based on
      the use of steroids and immunosuppressive drugs and aims to control the severity
      of acute attacks and to prevent relapses of the disease. This review gives an
      update of latest knowledge of NMOSD and NMO, emphasizing the novel diagnostic
      criteria and both current and future therapeutic approaches.

PMID- 29339317
TI  - Arterial stenosis in antiphospholipid syndrome: Update on the unrevealed
      mechanisms of an endothelial disease.
AB  - First described in 1983, antiphospholipid syndrome (APS) is an autoimmune
      condition characterized by the occurrence of recurrent arterial and/or venous
      thrombosis, and/or pregnancy morbidity, in the setting of persistent presence of
      antiphospholipid antibodies (aPL). While thrombosis is the most well-known
      pathogenic mechanism in this disorder, the relevance of some other mechanisms
      such as arterial stenosis is being increasingly recognized. Arterial stenosis has
      been first described in the renal arteries in patients with APS, however
      intracranial and coeliac arteries can also be involved with various and treatable
      clinical manifestations. The underlying pathophysiology of this stenotic arterial
      vasculopathy is not fully understood but some recent studies revealed new
      insights into the molecular mechanism behind this endothelial cell activation in
      APS. In this review, we discuss these newly discovered mechanisms and highlight
      the diagnostic and therapeutic modalities of the APS related arterial stenosis.

PMID- 29339318
TI  - Dietary patterns, body mass index and inflammation: Pathways to depression and
      mental health problems in adolescents.
AB  - BACKGROUND: Observational studies suggest that dietary patterns may impact mental
      health outcomes, although biologically plausible pathways are yet to be tested.
      We aimed to elucidate the longitudinal relationship between dietary patterns,
      adiposity, inflammation and mental health including depressive symptoms in a
      population-based cohort of adolescents. METHODS: Data were provided from 843
      adolescents participating in the Western Australian Pregnancy Cohort (Raine)
      Study at 14 and 17 years (y) of age. Structural equation modelling was applied to
      test our hypothesised models relating dietary patterns, energy intake and
      adiposity (body mass index) at 14 y to adiposity and the pro-inflammatory
      adipokine (leptin) and inflammation (high sensitivity C-reactive protein - hs
      CRP) at 17 y, and these inflammatory markers to depressive symptoms (Beck
      Depression Inventory) and Internalising and Externalising Behavioral Problems
      (Child Behavior Check List Youth Self- Report) at 17 y. We further tested a
      reverse hypothesis model, with depression at 14 y as a predictor of dietary
      patterns at the same time-point. RESULTS: The tested models provided a good fit
      to the data. A 'Western' dietary pattern (high intake of red meat, takeaway,
      refined foods, and confectionary) at 14 y was associated with higher energy
      intake and BMI at 14 y, and with BMI and biomarkers of inflammation at 17 y (all
      p < .05). A 'Healthy' dietary pattern (high in fruit, vegetables, fish, whole
      grains) was inversely associated with BMI and inflammation at 17 y (p < .05).
      Higher BMI at 14 y was associated with higher BMI (p < .01), leptin (p < .05), hs
      CRP (p < .05), depressive symptoms (p < .05) and mental health problems (p <
      .05), all at 17 y. CONCLUSION: A 'Western' dietary pattern associates with an
      increased risk of mental health problems including depressive symptoms in
      adolescents, through biologically plausible pathways of adiposity and
      inflammation, whereas a 'Healthy' dietary pattern appears protective in these
      pathways. Longitudinal modelling into adulthood is indicated to confirm the
      complex associations of dietary patterns, adiposity, inflammation and mental
      health problems, including depressive symptoms.

PMID- 29339319
TI  - Treatment with the noradrenaline re-uptake inhibitor atomoxetine alone and in
      combination with the alpha2-adrenoceptor antagonist idazoxan attenuates loss of
      dopamine and associated motor deficits in the LPS inflammatory rat model of
      Parkinson's disease.
AB  - The impact of treatment with the noradrenaline (NA) re-uptake inhibitor
      atomoxetine and the alpha2-adrenoceptor (AR) antagonist idazoxan in an animal
      model of Parkinson's disease (PD) was assessed. Concurrent systemic treatment
      with atomoxetine and idazoxan, a combination which serves to enhance the extra
      synaptic availability of NA, exerts anti-inflammatory and neuroprotective effects
      following delivery of an inflammatory stimulus, the bacterial endotoxin,
      lipopolysaccharide (LPS) into the substantia nigra. Lesion-induced deficits in
      motor function (akinesia, forelimb-use asymmetry) and striatal dopamine (DA) loss
      were rescued to varying degrees depending on the treatment. Treatment with
      atomoxetine following LPS-induced lesion to the substantia nigra, yielded a
      robust anti-inflammatory effect, suppressing microglial activation and expression
      of the pro-inflammatory cytokine TNF-alpha whilst increasing the expression of
      neurotrophic factors. Furthermore atomoxetine treatment prevented loss of
      tyrosine hydroxylase (TH) positive nigral dopaminergic neurons and resulted in
      functional improvements in motor behaviours. Atomoxetine alone was sufficient to
      achieve most of the observed effects. In combination with idazoxan, an additional
      improvement in the impairment of contralateral limb use 7 days post lesion and a
      reduction in amphetamine-mediated rotational asymmetry 14 days post-lesion was
      observed, compared to atomoxetine or idazoxan treatments alone. The results
      indicate that increases in central NA tone has the propensity to regulate the
      neuroinflammatory phenotype in vivo and may act as an endogenous neuroprotective
      mechanism where inflammation contributes to the progression of DA loss. In
      accordance with this, the clinical use of agents such as NA re-uptake inhibitors
      and alpha2-AR antagonists may prove useful in enhancing the endogenous
      neuroimmunomodulatory potential of NA in conditions associated with brain
      inflammation.

PMID- 29339320
TI  - Primary Obstruction of the Foramen of Luschka: Anatomy, Histology, and Clinical
      Significance.
AB  - BACKGROUND: The foramen of Luschka is a natural aperture between the fourth
      ventricle and the subarachnoid space at the cerebellopontine angle. Membranous
      closure of this foramen is referred to as primary obstruction. Available
      information about this variant and its role in the development of the cysts of
      the posterior fossa is contradictory. METHODS: The macroscopic and histologic
      features of the obstructed foramina were examined in 61 formalin-fixed human
      brains (122 foramina). Three rhomboid lips of various sizes with lateral recess
      were used for comparison. Five postoperative cases of diverticulum of the foramen
      of Luschka were included in this study, with 1 case presented in detail to
      illustrate anatomic and histologic findings. RESULTS: Primary obstruction was
      present in 11 of 122 cases. In 1 case, an enlarged rigid pouch with a thick wall
      was found. The wall of the membrane in primary obstruction and the rhomboid lip
      were composed of an inner ependymal, a middle glial, and an outer leptomeningeal
      layer. CONCLUSIONS: The rhomboid lip is a remnant of the roof of the fourth
      ventricle. Imperforation of the foramen of Luschka results in a pouch in the
      cerebellopontine angle that contains choroid plexus (Bochdalek's flower basket)
      and communicates with the fourth ventricle. This pouch has the potential to grow
      to a diverticulum and cause clinical symptoms. Based on our clinical
      observations, detailed radiologic and surgical-anatomic criteria were proposed to
      support the differential diagnosis of a diverticulum of the foramen of Luschka.
      Treatment strategies were also suggested.

PMID- 29339321
TI  - Internal Thoracic Artery to Middle Cerebral Artery Bypass Surgery: Cadaveric
      Feasibsility Study.
AB  - BACKGROUND: A few options of extracranial donor vessels exist for use in
      intracranial vascular bypass procedures. To our knowledge, the use of an internal
      thoracic artery for cerebral revascularization has not been studied previously.
      Hence, this cadaveric feasibility study was performed. METHODS: The internal
      thoracic artery was dissected in 5 adult cadaveric specimens. The proximal
      diameter, distal diameter, and length of the vessel were measured and recorded.
      The artery was then transected distally at the seventh intercostal space and
      transposed cranially, through a pterional craniotomy opening to reach the middle
      cerebral artery at the skull base. RESULTS: The mean diameter of the internal
      thoracic artery at its proximal end was 3.5 mm and at its distal end was 2 mm.
      The average length of the vessel was 31 cm. There was no statistical difference
      between the measurements recorded from different sides or sexes. In each
      specimen, an internal thoracic artery was dissected, rotated superiorly, and
      advanced subcutaneously behind the ear to reach the middle cerebral artery at the
      skull base without difficulty and remained tensionless at the site of
      anastomosis. CONCLUSIONS: In this cadaveric study, we demonstrated the
      suitability of the internal thoracic artery in use as a donor vessel for a single
      site anastomosis in a high-flow cerebral bypass procedure.

PMID- 29339322
TI  - Endoscopic Endonasal Craniofacial Surgery for Recurrent Skull Base Meningiomas
      Involving the Pterygopalatine Fossa, the Infratemporal Fossa, the Orbit, and the
      Paranasal Sinus.
AB  - OBJECTIVE: Skull base meningiomas carry a nonnegligible risk of recurrence. In
      particular, those arising from the sphenoid wings or middle cranial fossa
      penetrate into extracranial regions, uncommonly showing massive expansion into
      the craniofacial regions on recurrence. The role of endoscopic endonasal surgery
      for those intractable lesions remains unclear. METHODS: We performed endoscopic
      endonasal craniofacial surgery for 8 recurrent meningiomas invading into the
      pterygopalatine fossa, infratemporal fossa, nasopharynx, paranasal sinus, or
      orbit, comprising 2 meningothelial and 1 fibrous meningiomas (World Health
      Organization [WHO] grade I), 3 atypical and 1 clear cell meningiomas (grade II),
      and 1 anaplastic meningioma (grade III). All were large (15-80 cm3; median, 45
      cm3) and highly vascularized. RESULTS: All 8 tumors were sufficiently resected.
      Gross total resection of the craniofacial part of the lesions was achieved in 5
      patients (62.5%). In 3 patients with WHO grade I meningiomas and 1 with grade II,
      tumors were successfully controlled as of the last follow-up. In 4 patients with
      WHO grade II or III meningiomas, craniofacial lesions were controlled, whereas
      original intracranial lesions were poorly controlled and became critical.
      CONCLUSIONS: We consider the endoscopic endonasal approach as an acceptable, less
      invasive alternative for recurrent craniofacial meningioma. Although all these
      cases were relatively large and highly vascularized, preoperative endovascular
      embolization of the feeding arteries contributes to significantly reducing
      vascularity of the tumors, and local control of the craniofacial lesions was
      successfully achieved in all cases. Endoscopic endonasal craniofacial surgery
      enabled sufficient mass reduction without disfiguring facial incisions.

PMID- 29339323
TI  - Mechanical Thrombectomy of Acute Middle Cerebral Artery Occlusion Using Trans
      Anterior Communicating Artery Approach.
AB  - BACKGROUND: A cross-circulation technique involves gaining access to a cerebral
      vessel through a patent anterior or posterior communicating artery. This
      technique may be used in patients with emergent large-vessel occlusions and an
      unfavorable direct route to the occlusion. While few previous reports have
      demonstrated a successful cross-circulation technique for treatment of emergent
      large-vessel occlusions, we present the first 2 cases of transanterior
      communicating artery stent retriever thrombectomy. CASE DESCRIPTION: Case #1: A
      64-year-old female presented with acute right middle cerebral artery (MCA)
      occlusion. She demonstrated a "triple-tandem" brachiocephalic-internal carotid
      artery-middle cerebral artery occlusion, thus precluding direct access to the
      right MCA. Successful stent retriever mechanical thrombectomy was performed
      across the anterior communicating artery, using a left internal carotid artery
      approach. Case #2: A 70-year old female presented with acute occlusion of the
      left MCA and tandem occlusion of the cervical left internal carotid artery.
      Multiple attempts to catheterize the left common carotid artery were
      unsuccessful. She underwent successful stent retriever mechanical thrombectomy
      across a patent anterior communicating artery, using a right internal carotid
      artery approach. CONCLUSIONS: Timely recanalization of an occluded artery plays a
      critical role in the prognosis of patients with acute ischemic stroke. Successful
      stent retriever mechanical thrombectomy of an occluded MCA is possible using a
      transanterior communicating artery approach in patients without a direct access
      route to the occluded intracranial vessel. We review the pathophysiology of
      tandem lesions, access routes to intracranial occlusions, and the literature on
      cross-circulation techniques to treat emergent large-vessel occlusions.

PMID- 29339324
TI  - Oscillatory Synchronous Inhibition in the Basolateral Amygdala and its Primary
      Dependence on NR2A-containing NMDA Receptors.
AB  - Synchronous, rhythmic firing of GABAergic interneurons is a fundamental mechanism
      underlying the generation of brain oscillations, and evidence suggests that NMDA
      receptors (NMDARs) play a key role in oscillatory activity by regulating the
      activity of interneurons. Consistent with this, derangement of brain rhythms in
      certain neuropsychiatric disorders, notably schizophrenia and autism, is
      associated with NMDAR hypofunction and loss of inhibitory interneurons. In the
      basolateral amygdala (BLA)-dysfunction of which is involved in a host of
      neuropsychiatric diseases-, principal neurons display spontaneous, rhythmic
      "bursts" of inhibitory activity, which could potentially be involved in the
      orchestration of oscillations in the BLA network; here, we investigated the role
      of NMDARs in these inhibitory oscillations. Rhythmic bursts of spontaneous IPSCs
      (0.5 Hz average burst frequency) recorded from rat BLA principal cells were
      blocked or significantly suppressed by D-AP5, and could be driven by NMDAR
      activation alone. BLA interneurons generated spontaneous bursts of suprathreshold
      EPSCs at a similar frequency, which were also blocked or reduced by D-AP5. PEAQX
      (GluN2A-NMDAR antagonist; 0.4 MUM) or Ro-25-6981 (GluN2B-NMDAR antagonist; 5 MUM)
      suppressed the IPSC and EPSC bursts; suppression by PEAQX was significantly
      greater than that by Ro-25-6981. Immunohistochemical labeling revealed the
      presence of both GluN2A- and GluN2B-NMDARs on GABAergic BLA interneurons, while,
      functionally, GluN2A-NMDARs have the dominant role, as suggested by a greater
      reduction of NMDA-evoked currents by PEAQX versus Ro-25-6981. Entrainment of BLA
      principal neurons in an oscillatory generation of inhibitory activity depends
      primarily on activation of GluN2A-NMDARs, and interneuronal GluN2A-NMDARs may
      play a significant role.

PMID- 29339326
TI  - Surround Inhibition in the Primary Motor Cortex is Task-specifically Modulated in
      Non-professional Musicians but not in Healthy Controls During Real Piano Playing.
AB  - Research has indicated that at the onset of a finger movement, unwanted
      contractions of adjacent muscles are prevented by inhibiting the cortical areas
      representing these muscles. This so-called surround inhibition (SI) seems
      relevant for the performance of selective finger movements but may not be
      necessary for tasks involving functional coupling between different finger
      muscles. Therefore, the present study compared SI between isolated finger
      movement and complex selective finger movements while playing a three-finger
      sequence on the piano in nine non-professional musicians and 10 untrained control
      participants. Transcranial magnetic stimulation (TMS) was applied to the
      contralateral motor cortex to assess SI in the first dorsal interosseous (FDI),
      abductor pollicis brevis (APB) and abductor digiti minimi (ADM) during the
      movement preparation and the late phasic phases. The results reveal stronger SI
      during the preparation phase than during the phasic phase (30.6% vs. 10.7%; P <
      0.05) in the isolated-finger condition in both musicians and controls. Results
      also show higher SI in musicians during the preparation phase of the isolated
      finger condition compared to the preparation phase of the three-finger sequence
      (40% vs. 15%; P < 0.05). However, the control group did not show this task
      specific modulation of SI (isolated: 25% vs. sequence: 25%; P > 0.05). Thus,
      musicians were able to modulate SI between conditions whereas control
      participants revealed constant levels of SI. Therefore, it may be assumed that
      long-term training as observed in skilled musicians is accompanied by task
      specific effects on SI modulation potentially relating to the ability to perform
      selective and complex finger movements.

PMID- 29339325
TI  - Induction of Anti-agrin Antibodies Causes Myasthenia Gravis in Mice.
AB  - Myasthenia gravis (MG) is an autoimmune disorder of the neuromuscular junction
      (NMJ). Most cases of MG are caused by autoantibodies against the acetylcholine
      receptor (AChR), muscle-specific kinase (MuSK) and low-density lipoprotein
      receptor-related protein 4 (LRP4). Recent studies have identified anti-agrin
      antibodies in MG patients lacking these three antibodies (i.e., triple negative
      MG). Agrin is a basal lamina protein that has two isoforms. Neural agrin (N
      agrin) binds to LRP4 to activate MuSK to induce AChR clusters and is thus
      critical for NMJ formation. We demonstrate that mice immunized with N-agrin
      showed MG-associated symptoms including muscle weakness, fragmented and distorted
      NMJs. These effects were not observed in mice injected with muscle agrin (M
      agrin), an isoform that is inactive in inducing AChR clusters. Treatment with
      anti-N-agrin, but not anti-M-agrin, antibodies reduced agrin-induced AChR
      clusters in muscle cells. Together, these observations suggest that agrin
      antibodies may be play a role in MG pathogenesis.

PMID- 29339327
TI  - The chaperonin CCT promotes the formation of fibrillar aggregates of gamma
      tubulin.
AB  - The type II chaperonin CCT is involved in the prevention of the pathogenesis of
      numerous human misfolding disorders, as it sequesters misfolded proteins, blocks
      their aggregation and helps them to achieve their native state. In addition, it
      has been reported that CCT can prevent the toxicity of non-client amyloidogenic
      proteins by the induction of non-toxic aggregates, leading to new insight in
      chaperonin function as an aggregate remodeling factor. Here we add experimental
      evidence to this alternative mechanism by which CCT actively promotes the
      formation of conformationally different aggregates of gamma-tubulin, a non
      amyloidogenic CCT client protein, which are mediated by specific CCT-gamma
      tubulin interactions. The in vitro-induced aggregates were in some cases long
      fiber polymers, which compete with the amorphous aggregates. Direct injection of
      unfolded purified gamma-tubulin into single-cell zebra fish embryos allowed us to
      relate this in vitro activity with the in vivo formation of intracellular
      aggregates. Injection of a CCT-binding deficient gamma-tubulin mutant
      dramatically diminished the size of the intracellular aggregates, increasing the
      toxicity of the misfolded protein. These results point to CCT having a role in
      the remodeling of aggregates, constituting one of its many functions in cellular
      proteostasis.

PMID- 29339328
TI  - Micro-morphological adaptations of the wing nodus to flight behaviour in four
      dragonfly species from the family Libellulidae (Odonata: Anisoptera).
AB  - Adult dragonflies can be divided into two major groups, perchers and fliers,
      exhibiting notably different flight behaviour. Previous studies have yielded
      conflicting results regarding the link between the wing macro-morphology and
      flight style in these two groups. In this study, we present the first systematic
      investigation of the micro-morphological differences of wings of percher and
      flier dragonflies in four closely related species from the family Libellulidae.
      Our results suggest that the shape and material composition of wing
      microstructural components and, in particular, the nodus are adapted to
      facilitate the specific wing functioning in fliers and perchers. The findings
      further indicate a decreasing trend in the area proportion of the soft resilin
      dominated cuticle in the nodus in the series of species from typical perchers to
      typical fliers. Such a reduction in the resilin proportion in the nodus of fliers
      is associated with an increase in the wing aspect ratio. The knot-shaped
      protrusion at the nodus of perchers, which becomes notably smaller in that of
      strong fliers, is likely to act as a mechanical stopper, avoiding large wing
      displacements. This study aims to develop a novel framework for future research
      on the relationship between wing morphology and flight behaviour in dragonflies.

PMID- 29339329
TI  - Pituitary size alteration and adverse effects of radiation therapy performed in 9
      dogs with pituitary-dependent hypercortisolism.
AB  - The purpose of this study was to determine the therapeutic and/or adverse effects
      of radiation therapy (RT) against pituitary tumors in dogs with pituitary
      dependent hypercortisolism, as monitored by frequent post-RT detailed MRI
      examinations, clinical signs, and changes in hormone concentrations. Nine dogs
      with an adrenocorticotropic hormone (ACTH)-secreting pituitary mass diagnosed by
      magnetic resonance imaging (MRI) underwent RT for 4weeks (total of 48Gy in 4-Gy
      fractions). Pituitary height/brain area (P/B) value, clinical signs, basal plasma
      ACTH concentrations, serum cortisol concentrations (pre- and post-ACTH
      stimulation test) and adverse effects of RT were evaluated before and post-RT.
      The P/B value was significantly lower in all nine dogs post-RT. One dog lacking
      any neurological signs demonstrated no change in clinical signs pre and post-RT.
      Out of 8 dogs which exhibited neurological signs pre-RT, half of them
      demonstrated complete resolution of their signs, whereas the other half showed
      transient resolution. In all animals with recurrence of neurological signs,
      pituitary tumor regrowth was not observed; however, MRI revealed moderate to
      severe pituitary hemorrhage. Late adverse effect (bilateral otitis media) was
      observed in three of nine dogs post-RT. RT did not induce any significant changes
      in the dogs' basal plasma ACTH concentration and pre- and post-ACTH serum
      cortisol concentrations. In conclusion, RT is effective to reduce pituitary size
      and the mass effect, but does not appear to affect blood hormone concentrations,
      necessitating additional medical treatment against hypercortisolism. Periodic MRI
      imaging post-RT enables early detection of adverse effects of RT.

PMID- 29339330
TI  - Photocatalytic degradation of aniline using an autonomous rotating drum reactor
      with both solar and UV-C artificial radiation.
AB  - The aim of this work was to evaluate the performance of a novel self-autonomous
      reactor technology (capable of working with solar irradiation and artificial UV
      light) for water treatment using aniline as model compound. This new reactor
      design overcomes the problems of the external mass transfer effect and the
      accessibility to photons occurring in traditional reaction systems. The UV-light
      source is located inside the rotating quartz drums (where TiO2 is immobilized),
      allowing light to easily reach the water and the TiO2 surface. Several processes
      (UV, H2O2, Solar, TiO2, Solar/TiO2, Solar/TiO2/H2O2 and UV/Solar/H2O2/TiO2) were
      tested. The synergy between Solar/H2O2 and Solar/TiO2 processes was quantified to
      be 40.3% using the pseudo-first-order degradation rate. The apparent photonic
      efficiency, zeta, was also determined for evaluating light utilization. For the
      Solar/TiO2/H2O2 process, the efficiency was found to be practically constant
      (0.638-0.681%) when the film thickness is in the range of 1.67-3.87 MUm. However,
      the efficiency increases up to 2.67% when artificial UV light was used in
      combination, confirming the efficient design of this installation. Thus, if
      needed, lamps can be switched on during cloudy days to improve the degradation
      rate of aniline and its mineralization. Under the optimal conditions selected for
      the Solar/TiO2/H2O2 process ([H2O2] = 250 mg/L; pH = 4, [TiO2] = 0.65-1.25
      mg/cm2), 89.6% of aniline is degraded in 120 min. If the lamps are switched on,
      aniline is completely degraded in 10 min, reaching 85% of mineralization in 120
      min. TiO2 was re-used during 5 reaction cycles without apparent loss in activity
      (<2%). Quantification of hydroxyl radicals and dissolved oxygen allows a chemical
      based explanation of the process. Finally, the UV/Solar/TiO2/H2O2 process was
      found to have lower operation costs than other systems described in literature
      (0.67 ?/m3).

PMID- 29339331
TI  - The catalytic destruction of antibiotic tetracycline by sulfur-doped manganese
      oxide (S-MgO) nanoparticles.
AB  - The present study evaluates the efficacy of S-doped MgO (S-MgO) as compared with
      the plain MgO as a catalyst for destructive removal of tetracycline (TTC) in
      aqueous solutions. The S-MgO had around 6% S in its structure. Doping MgO with S
      caused increase in surface oxygen vacancy defects. Adding S-MgO (12 g/L) to a TTC
      aqueous solution (50 mg/L) caused removal of around 99% TTC at the neutral pH
      (ca. 5.1) and a short reaction time of 10 min. In comparison, plain MgO could
      remove only around 15% of TTC under similar experimental conditions. Diffusing O2
      into the TTC solution under the reaction with S-MgO resulted in a considerable
      improvement of TTC removal as compared to diffusing N2. Complete removal of TTC
      and 86.4% removal of its TOC could be obtained using 2 g/L S-MgO nanoparticles.
      The removal of TTC increased with the increase in solution temperature. The
      presence of nitrate, sulfate and chloride did not considerably affect the removal
      of TTC using S-MgO while TTC removal significantly decreased at the presence of
      bicarbonate and phosphate. The S-MgO was a stable and reusable catalyst
      exhibiting much higher catalytic activity than plain MgO for the TTC destruction.
      Accordingly, S-MgO is an emerging and efficient catalyst for catalytic
      decomposition and mineralization of such pharmaceutical compounds as TTC under
      atmospheric temperature and pressure.

PMID- 29339332
TI  - Human perturbation increases the fluxes of dissolved molybdenum from land to
      ocean - The case of the Jiulong River in China.
AB  - Rivers contribute a substantial amount of trace metals including molybdenum (Mo)
      into the oceans. The driving forces controlling the riverine fluxes of dissolved
      metals still remain not fully understood. Our study then investigated the spatial
      variations of dissolved metals including molybdenum in a typically human
      perturbed river, the Jiulong River (JR), China. The aim of the study is to
      elucidate the relevance of anthropogenic perturbation on the fluxes of dissolved
      metals such as molybdenum from land to ocean. Our study shows a large spatial
      variability of dissolved Mo across tributary to main stream of the JR.
      Particularly, dissolved Mo was generally low (average: 5 +/- 1 nM) in the
      "pristine" JR headwaters, and elevated (19 +/- 6 nM) along the lower river
      continuum. Sporadically high levels of dissolved Mo occurred in the upper North
      River (77 +/- 19 nM), as a result of mining activities locally. Significant
      correlations of dissolved Mo with total dissolved solids (TDS) and dissolved
      strontium (Sr) were observed in the whole JR (Mo = 1.4* TDS -1.7, R2 = 0.86, p <
      .01; Mo = 1.2*Sr - 2.2, R2 = 0.70, p < .01, logarithmic scales). This indicates
      that dissolved Mo is mobilized mainly along with other major ions such as Sr
      during similar mineral dissolution processes. From the "pristine" headwaters to
      the mouth of the JR, riverine Mo fluxes at the mouth of the JR has elevated by at
      least 3 times due to human perturbation. Compiled historic data regarding metal
      fluxes from world rivers further confirmed that small and medium rivers are
      relatively more sensitive to human perturbation.

PMID- 29339333
TI  - Coral reefs for coastal protection: A new methodological approach and engineering
      case study in Grenada.
AB  - Coastal communities in tropical environments are at increasing risk from both
      environmental degradation and climate change and require urgent local adaptation
      action. Evidences show coral reefs play a critical role in wave attenuation but
      relatively little direct connection has been drawn between these effects and
      impacts on shorelines. Reefs are rarely assessed for their coastal protection
      service and thus not managed for their infrastructure benefits, while widespread
      damage and degradation continues. This paper presents a systematic approach to
      assess the protective role of coral reefs and to examine solutions based on the
      reef's influence on wave propagation patterns. Portions of the shoreline of
      Grenville Bay, Grenada, have seen acute shoreline erosion and coastal flooding.
      This paper (i) analyzes the historical changes in the shoreline and the local
      marine, (ii) assess the role of coral reefs in shoreline positioning through a
      shoreline equilibrium model first applied to coral reef environments, and (iii)
      design and begin implementation of a reef-based solution to reduce erosion and
      flooding. Coastline changes in the bay over the past 6 decades are analyzed from
      bathymetry and benthic surveys, historical imagery, historical wave and sea level
      data and modeling of wave dynamics. The analysis shows that, at present, the
      healthy and well-developed coral reefs system in the southern bay keeps the
      shoreline in equilibrium and stable, whereas reef degradation in the northern bay
      is linked with severe coastal erosion. A comparison of wave energy modeling for
      past bathymetry indicates that degradation of the coral reefs better explains
      erosion than changes in climate and historical sea level rise. Using this
      knowledge on how reefs affect the hydrodynamics, a reef restoration solution is
      designed and studied to ameliorate the coastal erosion and flooding. A
      characteristic design provides a modular design that can meet specific
      engineering, ecological and implementation criteria. Four pilot units were
      implemented in 2015 and are currently being field-tested. This paper presents one
      of the few existing examples available to date of a reef restoration project
      designed and engineered to deliver risk reduction benefits. The case study shows
      how engineering and ecology can work together in community-based adaptation. Our
      findings are particularly important for Small Island States on the front lines of
      climate change, who have the most to gain from protecting and managing coral
      reefs as coastal infrastructure.

PMID- 29339334
TI  - Eco-compensation in China: Theory, practices and suggestions for the future.
AB  - Eco-compensation is the most important form of compensatory conservation in
      China. However, this compensatory mechanism is criticized for vague definition
      and massive government participation. For better understanding of eco
      compensation in China, this paper compares theories and practices of compensatory
      mechanisms in China and abroad. The analysis of theoretical backgrounds shows
      that eco-compensation in China is a combination of 'ecological compensation' and
      'payments for ecosystem services'. Ten compensatory projects in China and abroad
      are assessed to reveal characteristics and problems of eco-compensation in China.
      The results show that compensatory projects in China lagged behind mature foreign
      compensatory projects in clarity of property rights, responsibility fulfillment,
      executive efficiency, effectiveness, sustainability and equality. The massive
      participation of the government is the major reason for the poor performance of
      compensatory projects in China. However, government participation is necessary at
      the present stage in China for the income gap and beneficiaries' low willingness
      to pay. For the improvement of eco-compensation in China, suggestions are given
      on the choice of non-market valuation methods, the creation of property rights
      and the establishment of market mechanisms.

PMID- 29339335
TI  - Potential impacts of offshore oil spills on polar bears in the Chukchi Sea.
AB  - Sea ice decline is anticipated to increase human access to the Arctic Ocean
      allowing for offshore oil and gas development in once inaccessible areas. Given
      the potential negative consequences of an oil spill on marine wildlife
      populations in the Arctic, it is important to understand the magnitude of impact
      a large spill could have on wildlife to inform response planning efforts. In this
      study we simulated oil spills that released 25,000 barrels of oil for 30 days in
      autumn originating from two sites in the Chukchi Sea (one in Russia and one in
      the U.S.) and tracked the distribution of oil for 76 days. We then determined the
      potential impact such a spill might have on polar bears (Ursus maritimus) and
      their habitat by overlapping spills with maps of polar bear habitat and movement
      trajectories. Only a small proportion (1-10%) of high-value polar bear sea ice
      habitat was directly affected by oil sufficient to impact bears. However, 27-38%
      of polar bears in the region were potentially exposed to oil. Oil consistently
      had the highest probability of reaching Wrangel and Herald islands, important
      areas of denning and summer terrestrial habitat. Oil did not reach polar bears
      until approximately 3 weeks after the spills. Our study found the potential for
      significant impacts to polar bears under a worst case discharge scenario, but
      suggests that there is a window of time where effective containment efforts could
      minimize exposure to bears. Our study provides a framework for wildlife managers
      and planners to assess the level of response that would be required to treat
      exposed wildlife and where spill response equipment might be best stationed.
      While the size of spill we simulated has a low probability of occurring, it
      provides an upper limit for planners to consider when crafting response plans.

PMID- 29339336
TI  - Organophosphate and brominated flame retardants in Australian indoor
      environments: Levels, sources, and preliminary assessment of human exposure.
AB  - Concentrations of nine organophosphate flame retardants (OPFRs) and eight
      polybrominated diphenyl ethers (PBDEs) were measured in samples of indoor dust (n
      = 85) and air (n = 45) from Australian houses, offices, hotels, and
      transportation (buses, trains, and aircraft). All target compounds were detected
      in indoor dust and air samples. Median ?9OPFRs concentrations were 40 MUg/g in
      dust and 44 ng/m3 in indoor air, while median ?8PBDEs concentrations were 2.1
      MUg/g and 0.049 ng/m3. Concentrations of FRs were higher in rooms that contained
      carpet, air conditioners, and various electronic items. Estimated daily intakes
      in adults are 14000 pg/kg body weight/day and 330 pg/kg body weight/day for
      ?9OPFRs and ?8PBDEs, respectively. Our results suggest that for the volatile FRs
      such as tris(2-chloroethyl) phosphate (TCEP) and TCIPP, inhalation is expected to
      be the more important intake pathway compared to dust ingestion and dermal
      contact.

PMID- 29339337
TI  - Adsorption of perfluoroalkyl substances on microplastics under environmental
      conditions.
AB  - Plastic debris has become an environmental problem during recent years. Among the
      plastic debris, microplastics (<5 mm; MPLs) imply an extra problem due to their
      capacity to enter into the fauna through ingestion. In this work, we study the
      capacity of three MPLs, that include high-density polyethylene (HDPE),
      polystyrene (PS) and polystyrene carboxylate (PS-COOH), to sorb 18 perfluoroalkyl
      substances (PFASs; including carboxylic acids, sulphonates and one sulphonamide)
      from the surrounding waters (freshwater and seawater). Conclusions drawn from the
      results are that perfluoro sulphonates and sulphonamides have more tendency to be
      sorbed onto MPLs. In addition, PS and PS-COOH have more affinity for PFASs than
      HDPE. Finally, the increment of conductivity and pH of the water decreases the
      exposure time that is necessary to reach equilibrium. However, the presence of
      salts decreases the tendency of PFASs to be sorbed onto plastic surfaces. These
      results highlight the problem associated with the presence of MPLs in inland and
      marine waters since toxic compounds can be sorbed onto surrounding plastics that
      could be ingested by aquatic fauna.

PMID- 29339338
TI  - The phytotoxicities of decabromodiphenyl ether (BDE-209) to different rice
      cultivars (Oryza sativa L.).
AB  - Decabromodiphenyl ether (BDE-209), as a major component of brominated flame
      retardants, has been detected in the agricultural soil in considerable amount.
      Given that BDE-209 is toxic, ubiquitous and persistent, BDE-209 might induce
      toxic effects on rice cultivars planted in contaminated soil. A comparative study
      was conducted on phytotoxicities and GC-MS based antioxidant-related metabolite
      levels to investigate the differences of phytotoxicities of BDE-209 to rice
      cultivars in Yangtze River Delta of China. Rice seedlings were treated with BDE
      209 at 0, 10, 50, 100 and 500 MUg/L in a hydroponic setup. Results showed that
      BDE-209-induced phytotoxicites were cultivar-dependent and that the antioxidant
      defense systems in the cultivars were disturbed differently. Among the three
      selected cultivars (Jiayou 5, Lianjing 7 and Yongyou 9), Jiayou 5 and Lianjing 7
      displayed lower toxic effects than Yongyou 9 in terms of the growth inhibition,
      lipid peroxidation and DNA damage. The increases of antioxidant enzymes were
      significantly higher in Jiayou 5 and Lianjing 7 than those in Yongyou 9.
      Multivariate analysis of antioxidant-related metabolites in the three cultivars
      indicated that l-tryptophan and l-valine were the most important ones among 10
      metabolites responsible for the separation of cultivars. The up-regulation of l
      tryptophan and l-valine were likely plant strategies to increase their tolerance.
      The current results provided an insight into the development of rice cultivars
      with higher BDE-209 tolerance.

PMID- 29339339
TI  - Proteomics and genetic analyses reveal the effects of arsenite oxidation on
      metabolic pathways and the roles of AioR in Agrobacterium tumefaciens GW4.
AB  - A heterotrophic arsenite [As(III)]-oxidizing bacterium Agrobacterium tumefaciens
      GW4 isolated from As(III)-rich groundwater sediment showed high As(III)
      resistance and could oxidize As(III) to As(V). The As(III) oxidation could
      generate energy and enhance growth, and AioR was the regulator for As(III)
      oxidase. To determine the related metabolic pathways mediated by As(III)
      oxidation and whether AioR regulated other cellular responses to As(III),
      isobaric tags for relative and absolute quantitation (iTRAQ) was performed in
      four treatments, GW4 (+AsIII)/GW4 (-AsIII), GW4-DeltaaioR (+AsIII)/GW4-DeltaaioR
      (-AsIII), GW4-DeltaaioR (-AsIII)/GW4 (-AsIII) and GW4-DeltaaioR (+AsIII)/GW4
      (+AsIII). A total of 41, 71, 82 and 168 differentially expressed proteins were
      identified, respectively. Using electrophoretic mobility shift assay (EMSA) and
      qRT-PCR, 12 genes/operons were found to interact with AioR. These results
      indicate that As(III) oxidation alters several cellular processes related to
      arsenite, such as As resistance (ars operon), phosphate (Pi) metabolism (pst/pho
      system), TCA cycle, cell wall/membrane, amino acid metabolism and
      motility/chemotaxis. In the wild type with As(III), TCA cycle flow is perturbed,
      and As(III) oxidation and fermentation are the main energy resources. However,
      when strain GW4-DeltaaioR lost the ability of As(III) oxidation, the TCA cycle is
      the main way to generate energy. A regulatory cellular network controlled by AioR
      is constructed and shows that AioR is the main regulator for As(III) oxidation,
      besides, several other functions related to As(III) are regulated by AioR in
      parallel.

PMID- 29339340
TI  - Bioavailability and soil-to-crop transfer of heavy metals in farmland soils: A
      case study in the Pearl River Delta, South China.
AB  - Soil-bound heavy metals are of great concern for human health due to the
      potential exposure via food chain transfer. In the present study, the occurrence,
      the bioavailability and the soil-to-crop transfer of heavy metals in farmland
      soils were investigated based on data from two agricultural areas, i.e. Sihui and
      Shunde in South China. Six heavy metals (As, Cu, Hg, Mn, Ni and Pb) were
      quantified in the farmland soils. The mean single pollution level indices (PI)
      were all lower than 1 except for Hg in soils from Shunde (PI = 1.51 +/- 0.46),
      suggesting the farmland soils were within clean and slightly polluted by heavy
      metals. As, Cu, Ni and Pb were found to be mostly present in the non-bioavailable
      form. The majority of Hg was considered potentially bioavailable, and Mn was
      found to be largely bioavailable. Soil pH was an important factor influencing
      bioavailability of soil-bound heavy metals. The concentrations of heavy metals in
      vegetables from Sihui and Shunde were within the food hygiene standards, while
      the rice grain from Sihui was polluted by Pb (PI = 10.3 +/- 23.4). Total soil
      concentrations of heavy metals were not correlated to their corresponding crop
      concentrations, instead, significant correlations were observed for bioavailable
      concentrations in soil. The results supported the notion that the bioavailability
      of the investigated heavy metals in the soil was largely responsible for their
      crop uptake. The soil-to-crop transfer factors based on bioavailable
      concentrations suggested that Cu, As and Hg in soils of the study area had
      greater tendency to be accumulated in the vegetables than other heavy metals,
      calling for further human health assessment by consuming the contaminated crops.

PMID- 29339341
TI  - Health status alterations in Ruditapes philippinarum after continuous secondary
      effluent exposure before and after additional tertiary treatment application.
AB  - A mobile pilot plant was set up in a wastewater treatment plant (WWTP) in
      southwest Spain to address potential adverse effects of effluents as a whole
      contaminant, which are discharging into marine environments. Ruditapes
      philippinarum specimens were exposed to different effluent concentrations (50%,
      25%, 12.5%, 6.25%, and 3.15%) during seven days. After effluent exposure,
      lysosomal membrane stability alterations (LMS), changes in the energy status
      storage (total lipids content (TLP) and in the mitochondrial electron transport
      (MET), inhibition of inflammatory mechanisms (cyclooxygenase activity (COX)), and
      neurotoxic effects (acetylcholinesterase (AChE) were determined in exposed
      organisms. Furthermore, potential toxic reduction in the effluent was analysed by
      the application of an additional microalgae tertiary treatment called
      photobiotreatment (PhtBio). Results after PhtBio confirmed the toxic effect
      reduction in exposed organisms. Neuroendocrine effects, alterations in energy
      budget and in lipid storage revealed alterations in clam's health status causing
      stress conditions after effluent exposure.

PMID- 29339342
TI  - Transgenerational impairments of reproduction and development of the marine
      invertebrate Crepidula onyx resulted from long-term dietary exposure of 2,2',4,4'
      tetrabromodiphenyl ether (BDE-47).
AB  - Polybrominated diphenyl ethers have become ubiquitous in the environment and
      elevated concentrations have often been found in marine organisms. Using the
      gastropod Crepidula onyx as a study model, this multigenerational study sets out
      to test the hypotheses that 1) parental dietary exposure to environmentally
      realistic levels of 2,2',4,4'-tetrabrominated diphenyl ether (BDE-47) would lead
      to transgenerational impairments on fitness traits of marine invertebrates, and
      2) the organisms might develop adaptation/acclimation after exposure for one or
      more generations. F0 generation of C. onyx was fed with the dinoflagellate
      Isochrysis galbana encapsulated with two concentrations of BDE-47 (1.78 and 16.0
      ng million cells-1, respectively), and half of the F1 offspring from the higher
      concentration treatment was returned to control condition (transgenerational
      group), while the other half received BDE-47 treatment continuously (continuous
      treatment group). Bioaccumulation and maternal transfer of BDE-47 were evident in
      all life stages of the F0 generation and in F1 eggs, respectively. Exposure to
      BDE-47 reduced fecundity, delayed sexual maturity, and impeded embryonic
      development in F0 to F2. In particular, developmental toxicity of F2 embryos was
      apparent in the transgenerational group, but not in the continuous treatment
      group, even when BDE-47 was not detected in the F2 embryos nor in their mothers
      and they have never been exposed to the chemical. This study also suggested that
      the offspring might have developed adaptation/acclimation to the exposure of BDE
      47 within two generations of exposure, and that the physiological alterations
      associated with acclimation/adaptation might have hindered the normal larval
      development under a stress free condition. These findings highlighted the need
      for long-term multigenerational studies in the ecological risk assessment of
      chemicals alike.

PMID- 29339343
TI  - An integrated evaluation of some faecal indicator bacteria (FIB) and chemical
      markers as potential tools for monitoring sewage contamination in subtropical
      estuaries.
AB  - Sewage input and the relationship between chemical markers (linear alkylbenzenes
      and coprostanol) and fecal indicator bacteria (FIB, Escherichia coli and
      enterococci), were evaluated in order to establish thresholds values for chemical
      markers in suspended particulate matter (SPM) as indicators of sewage
      contamination in two subtropical estuaries in South Atlantic Brazil. Both
      chemical markers presented no linear relationship with FIB due to high spatial
      microbiological variability, however, microbiological water quality was related
      to coprostanol values when analyzed by logistic regression, indicating that
      linear models may not be the best representation of the relationship between both
      classes of indicators. Logistic regression was performed with all data and
      separately for two sampling seasons, using 800 and 100 MPN 100 mL-1 of E. coli
      and enterococci, respectively, as the microbiological limits of sewage
      contamination. Threshold values of coprostanol varied depending on the FIB and
      season, ranging between 1.00 and 2.23 MUg g-1 SPM. The range of threshold values
      of coprostanol for SPM are relatively higher and more variable than those
      suggested in literature for sediments (0.10-0.50 MUg g-1), probably due to higher
      concentration of coprostanol in SPM than in sediment. Temperature may affect the
      relationship between microbiological indicators and coprostanol, since the
      threshold value of coprostanol found here was similar to tropical areas, but
      lower than those found during winter in temperate areas, reinforcing the idea
      that threshold values should be calibrated for different climatic conditions.

PMID- 29339344
TI  - Analysis and evaluation of (neuro)peptides in honey bees exposed to pesticides in
      field conditions.
AB  - During the last years, declines in honey bee colonies are being registered
      worldwide. Cholinergic pesticides and their extensive use have been correlated to
      the decline of pollinators and there is evidence that pesticides act as
      neuroendocrine disruptors affecting the metabolism of neuropeptides. However,
      there is a big absence of studies with quantitative results correlating the
      effect of pesticide exposure with changes on neuropeptides insects, and most of
      them are conducted under laboratory conditions, typically with individual active
      ingredients. In this study, we present an analytical workflow to evaluate
      pesticide effects on honey bees through the analysis of (neuro)peptides. The
      workflow consists of a rapid extraction method and liquid chromatography with
      triple quadrupole for preselected neuropeptides. For non-target analysis, high
      resolution mass spectrometry, multivariate analysis and automatic identification
      of discriminated peptides using a specific software and protein sequence
      databases. The analytical method was applied to the analysis of target and non
      target (neuro)peptides in honey bees with low and high content of a wide range of
      pesticides to which have been exposed in field conditions. Our findings show that
      the identification frequency of target neuropeptides decreases significantly in
      honey bees with high concentration of pesticides (pesticide concentrations >= 500
      MUg kg-1) in comparison with the honey bees with low content of pesticides
      (pesticide concentrations <= 20 MUg kg-1). Moreover, the principal component
      analysis in non-target search shows a clear distinction between peptide
      concentration in honey bees with high level of pesticides and honey bees with low
      level. The use of high resolution mass spectrometry has allowed the
      identification of 25 non-redundant peptides responsible for discrimination
      between the two groups, derived from 18 precursor proteins.

PMID- 29339345
TI  - Optimizing critical source control of five priority-regulatory trace elements
      from industrial wastewater in China: Implications for health management.
AB  - Anthropogenic emissions of toxic trace elements (TEs) have caused worldwide
      concern due to their adverse effects on human health and ecosystems. Based on a
      stochastic simulation of factors' probability distribution, we established a
      bottom-up model to estimate the amounts of five priority-regulatory TEs released
      to aquatic environments from industrial processes in China. Total TE emissions in
      China in 2010 were estimated at approximately 2.27 t of Hg, 310.09 t of As,
      318.17 t of Pb, 79.72 t of Cd, and 1040.32 t of Cr. Raw chemicals, smelting, and
      mining were the leading sources of TE emissions. There are apparent regional
      differences in TE pollution. TE emissions are much higher in eastern and central
      China than in the western provinces and are higher in the south than in the
      north. This spatial distribution was characterized in detail by allocating the
      emissions to 10 km * 10 km grid cells. Furthermore, the risk control for the
      overall emission grid was optimized according to each cell's emission and risk
      rank. The results show that to control 80% of TE emissions from major sources,
      the number of top-priority control cells would be between 200 and 400, and less
      than 10% of the total population would be positively affected. Based on TE risk
      rankings, decreasing the population weighted risk would increase the number of
      controlled cells by a factor of 0.3-0.5, but the affected population would
      increase by a factor of 0.8-1.5. In this case, the adverse effects on people's
      health would be reduced significantly. Finally, an optimized strategy to control
      TE emissions is proposed in terms of a cost-benefit trade-off. The estimates in
      this paper can be used to help establish a regional TE inventory and cyclic
      simulation, and it can also play supporting roles in minimizing TE health risks
      and maximizing resilience.

PMID- 29339346
TI  - User-Centered Design of Learn to Quit, a Smoking Cessation Smartphone App for
      People With Serious Mental Illness.
AB  - BACKGROUND: Smoking rates in the United States have been reduced in the past
      decades to 15% of the general population. However, up to 88% of people with
      psychiatric symptoms still smoke, leading to high rates of disease and mortality.
      Therefore, there is a great need to develop smoking cessation interventions that
      have adequate levels of usability and can reach this population. OBJECTIVE: The
      objective of this study was to report the rationale, ideation, design, user
      research, and final specifications of a novel smoking cessation app for people
      with serious mental illness (SMI) that will be tested in a feasibility trial.
      METHODS: We used a variety of user-centered design methods and materials to
      develop the tailored smoking cessation app. This included expert panel guidance,
      a set of design principles and theory-based smoking cessation content,
      development of personas and paper prototyping, usability testing of the app
      prototype, establishment of app's core vision and design specification, and
      collaboration with a software development company. RESULTS: We developed Learn to
      Quit, a smoking cessation app designed and tailored to individuals with SMI that
      incorporates the following: (1) evidence-based smoking cessation content from
      Acceptance and Commitment Therapy and US Clinical Practice Guidelines for smoking
      cessation aimed at providing skills for quitting while addressing mental health
      symptoms, (2) a set of behavioral principles to increase retention and
      comprehension of smoking cessation content, (3) a gamification component to
      encourage and sustain app engagement during a 14-day period, (4) an app structure
      and layout designed to minimize usability errors in people with SMI, and (5) a
      set of stories and visuals that communicate smoking cessation concepts and skills
      in simple terms. CONCLUSIONS: Despite its increasing importance, the design and
      development of mHealth technology is typically underreported, hampering
      scientific innovation. This report describes the systematic development of the
      first smoking cessation app tailored to people with SMI, a population with very
      high rates of nicotine addiction, and offers new design strategies to engage this
      population. mHealth developers in smoking cessation and related fields could
      benefit from a design strategy that capitalizes on the role visual engagement,
      storytelling, and the systematic application of behavior analytic principles to
      deliver evidence-based content.

PMID- 29339347
TI  - Hospital-Owned Apps in Taiwan: Nationwide Survey.
AB  - BACKGROUND: Over the last decade, the use of mobile phone apps in the health care
      industry has grown rapidly. Owing to the high penetration rate of Internet use in
      Taiwan, hospitals are eager to provide their own apps to improve the
      accessibility of medical care for patients. OBJECTIVE: The aims of this study
      were to provide an overview of the currently available hospital-owned apps in
      Taiwan and to conduct a cross-hospital comparison of app features. METHODS: In
      May 2017, the availability of apps from all 414 hospitals in Taiwan was surveyed
      from the hospital home pages and the Google Play app store. The features of the
      downloaded apps were then examined in detail and, for each app, the release date
      of the last update, download frequency, and rating score were obtained from
      Google Play. RESULTS: Among all the 414 hospitals in Taiwan, 150 (36.2%) owned
      Android apps that had been made available for public use, including 95% (18/19)
      of the academic medical centers, 77% (63/82) of the regional hospitals, and 22.0%
      (69/313) of the local community hospitals. Among the 13 different functionalities
      made available by the various hospital-owned apps, the most common were the
      doctor search (100%, 150/150), real-time queue monitoring (100%, 150/150), and
      online appointment scheduling (94.7%, 142/150) functionalities. The majority of
      apps (57.3%, 86/150) had a rating greater than 4 out of 5, 49.3% (74/150) had
      been updated at some point in 2017, and 36.0% (54/150) had been downloaded 10,000
      to 50,000 times. CONCLUSIONS: More than one-third of the hospitals owned apps
      intended to increase patient access to health care. The most common app features
      might reflect the health care situation in Taiwan, where the overcrowded
      outpatient departments of hospitals operate in an open-access mode without any
      strict referral system. Further research should focus on the effectiveness and
      safety of these apps.

PMID- 29339349
TI  - Jeremy Hunt's new department: major overhaul or window dressing?

PMID- 29339348
TI  - Evaluation Criteria of Noninvasive Telemonitoring for Patients With Heart
      Failure: Systematic Review.
AB  - BACKGROUND: Telemonitoring can improve heart failure (HF) management, but there
      is no standardized evaluation framework to comprehensively evaluate its impact.
      OBJECTIVE: Our objectives were to list the criteria used in published evaluations
      of noninvasive HF telemonitoring projects, describe how they are used in the
      evaluation studies, and organize them into a consistent scheme. METHODS: Articles
      published from January 1990 to August 2015 were obtained through MEDLINE, Web of
      Science, and EMBASE. Articles were eligible if they were original reports of a
      noninvasive HF telemonitoring evaluation study in the English language. Studies
      of implantable telemonitoring devices were excluded. Each selected article was
      screened to extract the description of the telemonitoring project and the
      evaluation process and criteria. A qualitative synthesis was performed. RESULTS:
      We identified and reviewed 128 articles leading to 52 evaluation criteria
      classified into 6 dimensions: clinical, economic, user perspective, educational,
      organizational, and technical. The clinical and economic impacts were evaluated
      in more than 70% of studies, whereas the educational, organizational, and
      technical impacts were studied in fewer than 15%. User perspective was the most
      frequently covered dimension in the development phase of telemonitoring projects,
      whereas clinical and economic impacts were the focus of later phases.
      CONCLUSIONS: Telemonitoring evaluation frameworks should cover all 6 dimensions
      appropriately distributed along the telemonitoring project lifecycle. Our next
      goal is to build such a comprehensive evaluation framework for telemonitoring and
      test it on an ongoing noninvasive HF telemonitoring project.

PMID- 29339350
TI  - Correction: The constant threat from a non-native predator increases tail muscle
      and fast-start swimming performance in Xenopus tadpoles.

PMID- 29339351
TI  - High-Target Versus Low-Target Blood Pressure Management During Cardiopulmonary
      Bypass to Prevent Cerebral Injury in Cardiac Surgery Patients: A Randomized
      Controlled Trial.
AB  - BACKGROUND: Cerebral injury is an important complication after cardiac surgery
      with the use of cardiopulmonary bypass. The rate of overt stroke after cardiac
      surgery is 1% to 2%, whereas silent strokes, detected by diffusion-weighted
      magnetic resonance imaging, are found in up to 50% of patients. It is unclear
      whether a higher versus a lower blood pressure during cardiopulmonary bypass
      reduces cerebral infarction in these patients. METHODS: In a patient- and
      assessor-blinded randomized trial, we allocated patients to a higher (70-80 mm
      Hg) or lower (40-50 mm Hg) target for mean arterial pressure by the titration of
      norepinephrine during cardiopulmonary bypass. Pump flow was fixed at 2.4 L.min
      1.m-2. The primary outcome was the total volume of new ischemic cerebral lesions
      (summed in millimeters cubed), expressed as the difference between diffusion
      weighted imaging conducted preoperatively and again postoperatively between days
      3 and 6. Secondary outcomes included diffusion-weighted imaging-evaluated total
      number of new ischemic lesions. RESULTS: Among the 197 enrolled patients, mean
      (SD) age was 65.0 (10.7) years in the low-target group (n=99) and 69.4 (8.9)
      years in the high-target group (n=98). Procedural risk scores were comparable
      between groups. Overall, diffusion-weighted imaging revealed new cerebral lesions
      in 52.8% of patients in the low-target group versus 55.7% in the high-target
      group (P=0.76). The primary outcome of volume of new cerebral lesions was
      comparable between groups, 25 mm3 (interquartile range, 0-118 mm3; range, 0-25
      261 mm3) in the low-target group versus 29 mm3 (interquartile range, 0-143 mm3;
      range, 0-22 116 mm3) in the high-target group (median difference estimate, 0; 95%
      confidence interval, -25 to 0.028; P=0.99), as was the secondary outcome of
      number of new lesions (1 [interquartile range, 0-2; range, 0-24] versus 1
      [interquartile range, 0-2; range, 0-29] respectively; median difference estimate,
      0; 95% confidence interval, 0-0; P=0.71). No significant difference was observed
      in frequency of severe adverse events. CONCLUSIONS: Among patients undergoing on
      pump cardiac surgery, targeting a higher versus a lower mean arterial pressure
      during cardiopulmonary bypass did not seem to affect the volume or number of new
      cerebral infarcts. CLINICAL TRIAL REGISTRATION: URL:
      https://www.clinicaltrials.gov. Unique identifier: NCT02185885.

PMID- 29339353
TI  - Correction: Prevention of Colitis and Colitis-Associated Colorectal Cancer by a
      Novel Polypharmacological Histone Deacetylase Inhibitor.

PMID- 29339354
TI  - Correction: Phase Ib/II Study of the Safety and Efficacy of Combination Therapy
      with Multikinase VEGF Inhibitor Pazopanib and MEK Inhibitor Trametinib In
      Advanced Soft Tissue Sarcoma.

PMID- 29339355
TI  - Re-Evaluation of the Normal Range of Serum Total CO2 Concentration.
AB  - A reliable determination of blood pH, PCO2, and [HCO3-] is necessary for
      assessing the acid-base status of a patient. However, most acid-base disorders
      are first recognized through abnormalities in serum total CO2 concentration
      ([TCO2]) in venous blood, a surrogate for [HCO3-]. In screening patients on the
      basis of serum [TCO2], we have been concerned about the wide limits of normal for
      serum [TCO2], 10-13 mEq/L, reported by many clinical laboratories. Indeed, we
      have encountered patients with serum [TCO2] values within the lower or upper end
      of the normal range of the reporting laboratory, who subsequently were shown to
      have a cardinal acid-base disorder.Here, we present a patient who had a serum
      [TCO2] within the lower end of the normal range of the clinical laboratory, which
      resulted in delayed diagnosis of a clinically important "hidden" acid-base
      disorder. To better define the appropriate limits of normal for serum [TCO2], we
      derived the expected normal range in peripheral venous blood in adults at sea
      level from carefully conducted acid-base studies. We then compared this range, 23
      to 30 mEq/L, to that reported by 64 clinical laboratories, 2 large commercial
      clinical laboratories, and the major textbook of clinical chemistry. For the most
      part, the range in the laboratories we queried was substantially different than
      that we derived and that published in the textbook, with some laboratories
      reporting values as low as 18-20 mEq/L and as high as 33-35 mEq/L. We conclude
      that the limits of values of serum [TCO2] reported by clinical laboratories are
      very often inordinately wide and not consistent with the range of normal expected
      in healthy individuals at sea level. We suggest that the limits of normal of
      serum [TCO2] at sea level be tightened to 23-30 mEq/L. Such correction will
      ensure recognition of the majority of "hidden" acid-base disorders.

PMID- 29339356
TI  - Kidney Biomarkers and Decline in eGFR in Patients with Type 2 Diabetes.
AB  - BACKGROUND AND OBJECTIVES: Biomarkers may improve identification of individuals
      at risk of eGFR decline who may benefit from intervention or dialysis planning.
      However, available biomarkers remain incompletely validated for risk
      stratification and prediction modeling. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: We examined serum cystatin C, urinary kidney injury molecule-1
      (uKIM-1), and urinary neutrophil gelatinase-associated lipocalin (UNGAL) in 5367
      individuals with type 2 diabetes mellitus and recent acute coronary syndromes
      enrolled in the Examination of Cardiovascular Outcomes with Alogliptin versus
      Standard of Care (EXAMINE) trial. Baseline concentrations and 6-month changes in
      biomarkers were also evaluated. Cox proportional regression was used to assess
      associations with a 50% decrease in eGFR, stage 5 CKD (eGFR<15 ml/min per 1.73
      m2), or dialysis. RESULTS: eGFR decline occurred in 98 patients (1.8%) over a
      median of 1.5 years. All biomarkers individually were associated with higher risk
      of eGFR decline (P<0.001). However, when adjusting for baseline eGFR,
      proteinuria, and clinical factors, only baseline cystatin C (adjusted hazard
      ratio per 1 SD change, 1.66; 95% confidence interval, 1.41 to 1.96; P<0.001) and
      6-month change in urinary neutrophil gelatinase-associated lipocalin (adjusted
      hazard ratio per 1 SD change, 1.07; 95% confidence interval, 1.02 to 1.12;
      P=0.004) independently associated with CKD progression. A base model for
      predicting kidney function decline with nine standard risk factors had strong
      discriminative ability (C-statistic 0.93). The addition of baseline cystatin C
      improved discrimination (C-statistic 0.94), but it failed to reclassify risk
      categories of individuals with and without eGFR decline. CONCLUSIONS: The
      addition of cystatin C or biomarkers of tubular injury did not meaningfully
      improve the prediction of eGFR decline beyond common clinical factors and routine
      laboratory data in a large cohort of patients with type 2 diabetes and recent
      acute coronary syndrome. PODCAST: This article contains a podcast at
      https://www.asn
      online.org/media/podcast/CJASN/2018_01_16_CJASNPodcast_18_3_G.mp3.

PMID- 29339357
TI  - Family History and Risk of Second Primary Breast Cancer after In Situ Breast
      Carcinoma.
AB  - Background: Incidence rates of in situ breast carcinomas have increased due to
      widespread adoption of mammography. Very little is known about why some women
      with in situ breast cancer later develop second primary breast cancers.Methods:
      In this population-based nested case-control study among in situ breast cancer
      survivors, including 539 cases with a second primary breast cancer and 994
      matched controls, we evaluated the association between first-degree family
      history of breast cancer and risk of developing a second primary breast
      cancer.Results: First-degree family history of breast cancer was associated with
      an increased risk of developing a second primary breast cancer among women with a
      previous in situ breast cancer [odds ratio (OR) = 1.33, 95% confidence interval
      (CI), 1.05-1.69] and those with two or more affected first-degree relatives had
      an even higher risk (OR = 1.94; 95% CI, 1.15-3.28). Those whose relative was
      diagnosed at less than 50 years old were more likely to develop a second primary
      breast cancer (OR = 1.78; 95% CI, 1.24-2.57). No difference in risks associated
      with number or age of affected relatives was observed by menopausal
      status.Conclusions: Results from this study suggest that first-degree family
      history of breast cancer may be an important risk factor for development of a
      second primary breast cancer among women with a previous in situ breast
      cancer.Impact: Given the growing population of in situ breast cancer survivors, a
      better understanding of risk factors associated with development of a second
      primary breast cancer is needed to further understand risk. Cancer Epidemiol
      Biomarkers Prev; 27(3); 315-20. (c)2018 AACR.

PMID- 29339360
TI  - First Comprehensive Companion Diagnostic OK'd.
AB  - The FDA has approved F1CDx, a comprehensive companion diagnostic test that can
      detect genetic alterations and two genomic signatures in any type of solid tumor.
      Patients with five common types of advanced cancer can be matched to one of 17
      targeted therapies with this single test.

PMID- 29339358
TI  - Family History of Cancer and Risk of Biliary Tract Cancers: Results from the
      Biliary Tract Cancers Pooling Project.
AB  - Background: Although some familial cancer syndromes include biliary tract cancers
      (BTCs; cancers of the gallbladder, intrahepatic and extrahepatic bile ducts, and
      ampulla of Vater), the few studies that have examined the relationships between
      family history of cancer (FHC) and BTCs have reported inconclusive findings. The
      objective of this study was to investigate the associations of FHC with risk of
      BTC in the Biliary Tract Cancers Pooling Project (BiTCaPP).Methods: We used Cox
      proportional hazards regressions models to estimate HRs and 95% confidence
      intervals for associations between FHC (any, first-degree, in female relative, in
      male relative, relative with gastrointestinal cancer, and relative with
      hormonally related cancer) and BTC risk by anatomic site within the biliary
      tract, adjusting for sex and race/ethnicity. Sensitivity analyses were conducted
      that restricted to studies reporting cholecystectomy data and to people without a
      history of cholecystectomy.Results: Data on FHC were available from 12
      prospective studies within BiTCaPP, which collectively contributed 2,246 cases
      (729 gallbladder, 345 intrahepatic and 615 extrahepatic bile duct, and 385
      ampulla of Vater cancers) with 21,706,107 person-years of follow-up. A marginal,
      inverse association between FHC and gallbladder cancer was driven to the null
      when analysis was restricted to studies reporting cholecystectomy data and to
      people without a history of cholecystectomy. FHC was not associated with risk of
      BTC at the other anatomic sites.Conclusions: These findings do not support an
      association between FHC and BTCs.Impact: In a study of 1.5 million people, FHC is
      not a risk factor for BTCs. Cancer Epidemiol Biomarkers Prev; 27(3); 348-51.
      (c)2018 AACR.

PMID- 29339361
TI  - David Oliver: Will we now see a serious attempt to tackle social care funding?

PMID- 29339359
TI  - Genetic Variants in Immune-Related Pathways and Breast Cancer Risk in African
      American Women in the AMBER Consortium.
AB  - Background: Constitutional immunity shaped by exposure to endemic infectious
      diseases and parasitic worms in Sub-Saharan Africa may play a role in the
      etiology of breast cancer among African American (AA) women.Methods: A total of
      149,514 gene variants in 433 genes across 45 immune pathways were analyzed in the
      AMBER consortium among 3,663 breast cancer cases and 4,687 controls. Gene-based
      pathway analyses were conducted using the adaptive rank truncated product
      statistic for overall breast cancer risk, and risk by estrogen receptor (ER)
      status. Unconditional logistic regression analysis was used to estimate ORs and
      95% confidence intervals (CIs) for single variants.Results: The top pathways were
      Interleukin binding (P = 0.01), Biocarta TNFR2 (P = 0.005), and positive
      regulation of cytokine production (P = 0.024) for overall, ER+, and ER- cancers,
      respectively. The most significant gene was IL2RB (P = 0.001) for overall cancer,
      with rs228952 being the top variant identified (OR = 0.85; 95% CI, 0.79-0.92).
      Only BCL3 contained a significant variant for ER+ breast cancer. Variants in
      IL2RB, TLR6, IL8, PRKDC, and MAP3K1 were associated with ER- disease. The only
      genes showing heterogeneity between ER- and ER+ cancers were TRAF1, MAP3K1, and
      MAPK3 (P <= 0.02). We also noted genes associated with autoimmune and atopic
      disorders.Conclusions: Findings from this study suggest that genetic variants in
      immune pathways are relevant to breast cancer susceptibility among AA women, both
      for ER+ and ER- breast cancers.Impact: Results from this study extend our
      understanding of how inherited genetic variation in immune pathways is relevant
      to breast cancer susceptibility. Cancer Epidemiol Biomarkers Prev; 27(3); 321-30.
      (c)2018 AACR.

PMID- 29339362
TI  - Circulation: Arrhythmia and Electrophysiology Editors and Editorial Board.

PMID- 29339363
TI  - In This Issue: January.

PMID- 29339365
TI  - Under pressure: meeting demand safely means knowing when to shout for help.

PMID- 29339364
TI  - Wider effects of the Bawa-Garba case on medical practice and public safety.

PMID- 29339366
TI  - Healthcare in Trump's first year.

PMID- 29339368
TI  - GMC's push for erasure of paediatrician is questionable.

PMID- 29339370
TI  - Nature's Wastebasket: The Role of the External Carotid Artery in Acute Stroke.
AB  - We describe a novel technical approach to acute stroke illustrated by the case of
      a 41 year old male who presented with tandem right common carotid artery (CCA)
      and M1 occlusions. His NIHSS was 17 and Alberta stroke programe early CT score
      (ASPECTs) was 8. Thrombectomy initially proved challenging due to large volume
      CCA thrombus that repeatedly occluded the aspiration catheters. However, by
      inflating a balloon distally and pulling clot into the adjacent ECA, we were able
      to quickly restore distal contrast flow to the intracranial circulation and
      achieve Thrombolysis In Cerebral Infarction/Arterial Occlusive Lesion
      (TICI2C/AOL3) revascularization.

PMID- 29339372
TI  - Correction: Mismatch Repair Proteins Initiate Epigenetic Alterations during
      Inflammation-Driven Tumorigenesis.

PMID- 29339373
TI  - A year in health and healthcare under President Trump.

PMID- 29339374
TI  - Multicenter evaluation of a new closed system drug-transfer device in reducing
      surface contamination by antineoplastic hazardous drugs.
AB  - PURPOSE: Results of a study to evaluate the effectiveness of a recently
      introduced closed system drug-transfer device (CSTD) in reducing surface
      contamination during compounding and simulated administration of antineoplastic
      hazardous drugs (AHDs) are reported. METHODS: Wipe samples were collected from 6
      predetermined surfaces in compounding and infusion areas of 13 U.S. cancer
      centers to establish preexisting levels of surface contamination by 2 marker AHDs
      (cyclophosphamide and fluorouracil). Stainless steel templates were placed over
      the 6 previously sampled surfaces, and the marker drugs were compounded and
      infused per a specific protocol using all components of the CSTD. Wipe samples
      were collected from the templates after completion of tasks and analyzed for both
      marker AHDs. RESULTS: Aggregated results of wipe sampling to detect preexisting
      contamination at the 13 study sites showed that overall, 66.7% of samples (104 of
      156) had detectable levels of at least 1 marker AHD; subsequent testing after
      CSTD use per protocol found a sample contamination rate of 5.8% (9 of 156
      samples). In the administration areas alone, the rate of preexisting
      contamination was 78% (61 of 78 samples); with use of the CSTD protocol, the
      contamination rate was 2.6%. Twenty-six participants rated the CSTD for ease of
      use, with 100% indicating that they were satisfied or extremely satisfied.
      CONCLUSION: A study involving a rigorous protocol and 13 cancer centers across
      the United States demonstrated that the CSTD reduced surface contamination by
      cyclophosphamide and fluorouracil during compounding and simulated
      administration. Participants reported that the CSTD was easy to use.

PMID- 29339375
TI  - TUSC2 Immunogene Therapy Synergizes with Anti-PD-1 through Enhanced Proliferation
      and Infiltration of Natural Killer Cells in Syngeneic Kras-Mutant Mouse Lung
      Cancer Models.
AB  - Expression of the multikinase inhibitor encoded by the tumor suppressor gene
      TUSC2 (also known as FUS1) is lost or decreased in non-small cell lung carcinoma
      (NSCLC). TUSC2 delivered systemically by nanovesicles has mediated tumor
      regression in clinical trials. Because of the role of TUSC2 in regulating immune
      cells, we assessed TUSC2 efficacy on antitumor immune responses alone and in
      combination with anti-PD-1 in two Kras-mutant syngeneic mouse lung cancer models.
      TUSC2 alone significantly reduced tumor growth and prolonged survival compared
      with anti-PD-1. When combined, this effect was significantly enhanced, and
      correlated with a pronounced increases in circulating and splenic natural killer
      (NK) cells and CD8+ T cells, and a decrease in regulatory T cells (Tregs),
      myeloid-derived suppressor cells (MDSCs), and T-cell checkpoint receptors PD-1,
      CTLA-4, and TIM-3. TUSC2 combined with anti-PD-1 induced tumor infiltrating more
      than NK and CD8+ T cells and fewer MDSCs and Tregs than each agent alone, both in
      subcutaneous tumor and in lung metastases. NK-cell depletion abrogated the
      antitumor effect and Th1-mediated immune response of this combination, indicating
      that NK cells mediate TUSC2/anti-PD-1 synergy. Release of IL15 and IL18 cytokines
      and expression of the IL15Ralpha chain and IL18R1 were associated with NK-cell
      activation by TUSC2. Immune response-related gene expression in the tumor
      microenvironment was altered by combination treatment. These data provide a
      rationale for immunogene therapy combined with immune checkpoint blockade in the
      treatment of NSCLC. Cancer Immunol Res; 6(2); 163-77. (c)2018 AACR.

PMID- 29339376
TI  - Tumor Immunity and Survival as a Function of Alternative Neopeptides in Human
      Cancer.
AB  - The immune system exerts antitumor activity via T cell-dependent recognition of
      tumor-specific antigens. Although the number of tumor neopeptides-peptides
      derived from somatic mutations-often correlates with immune activity and
      survival, most classically defined high-affinity neopeptides (CDNs) are not
      immunogenic, and only rare CDNs have been linked to tumor rejection. Thus, the
      rules of tumor antigen recognition remain incompletely understood. Here, we
      analyzed neopeptides, immune activity, and clinical outcome from 6,324 patients
      across 27 tumor types. We characterized a class of "alternatively defined
      neopeptides" (ADNs), which are mutant peptides predicted to bind MHC (class I or
      II) with improved affinity relative to their nonmutated counterpart. ADNs are
      abundant and molecularly distinct from CDNs. The load of ADNs correlated with
      intratumoral T-cell responses and immune suppression, and ADNs were also strong
      predictors of patient survival across tumor types. These results expand the
      spectrum of mutation-derived tumor antigens with potential clinical relevance.
      Cancer Immunol Res; 6(3); 1-12. (c)2018 AACR.

PMID- 29339378
TI  - Smartphone GP consultation app cost CCG L150 000 in first two months.

PMID- 29339379
TI  - Correction: Lipid signaling to membrane proteins: From second messengers to
      membrane domains and adapter-free endocytosis.

PMID- 29339377
TI  - Robust Antitumor Responses Result from Local Chemotherapy and CTLA-4 Blockade.
AB  - Clinical responses to immunotherapy have been associated with augmentation of
      preexisting immune responses, manifested by heightened inflammation in the tumor
      microenvironment. However, many tumors have a noninflamed microenvironment, and
      response rates to immunotherapy in melanoma have been <50%. We approached this
      problem by utilizing immunotherapy (CTLA-4 blockade) combined with chemotherapy
      to induce local inflammation. In murine models of melanoma and prostate cancer,
      the combination of chemotherapy and CTLA-4 blockade induced a shift in the
      cellular composition of the tumor microenvironment, with infiltrating CD8+ and
      CD4+ T cells increasing the CD8/Foxp3 T-cell ratio. These changes were associated
      with improved survival of the mice. To translate these findings into a clinical
      setting, 26 patients with advanced melanoma were treated locally by isolated limb
      infusion with the nitrogen mustard alkylating agent melphalan followed by
      systemic administration of CTLA-4 blocking antibody (ipilimumab) in a phase II
      trial. This combination of local chemotherapy with systemic checkpoint blockade
      inhibitor resulted in a response rate of 85% at 3 months (62% complete and 23%
      partial response rate) and a 58% progression-free survival at 1 year. The
      clinical response was associated with increased T-cell infiltration, similar to
      that seen in the murine models. Together, our findings suggest that local
      chemotherapy combined with checkpoint blockade-based immunotherapy results in a
      durable response to cancer therapy. Cancer Immunol Res; 6(2); 189-200. (c)2018
      AACR.

PMID- 29339381
TI  - Cholecystokinin is involved in triglyceride fatty acid uptake by rat adipose
      tissue.
AB  - The incorporation of plasma triglyceride (TG) fatty acids to white adipose tissue
      (WAT) depends on lipoprotein lipase (LPL), which is regulated by angiopoietin
      like protein-4 (ANGPTL-4), an unfolding molecular chaperone that converts active
      LPL dimers into inactive monomers. The production of ANGPTL-4 is promoted by
      fasting and repressed by feeding. We hypothesized that the postprandial hormone
      cholecystokinin (CCK) facilitates the storage of dietary TG fatty acids in WAT by
      regulating the activity of the LPL/ANGPTL-4 axis and that it does so by acting
      directly on CCK receptors in adipocytes. We report that administration of CCK-8
      (a bioactive fragment of CCK) to rats: (i) reduces plasma ANGTPL-4 levels; (ii)
      represses Angptl-4 expression in WAT and (iii) simultaneously enhances LPL
      activity in this tissue without inducing Lpl expression. In vivo CCK-8 effects
      are specifically antagonized by the CCK-2 receptor (CCK-2R) antagonist, L
      365,260. Moreover, CCK-8 downregulates Angptl-4 expression in wild-type pre
      adipocytes, an effect that is not observed in engineered pre-adipocytes lacking
      CCK-2R. These effects have functional consequences as CCK-8 was found to promote
      the uptake of dietary fatty acids by WAT, as demonstrated by means of proton
      nuclear magnetic resonance (1H-NMR). The efficacy of acute CCK-8 administration
      was not reduced after chronic CCK-8 treatment. Moreover, the effects of CCK-8 on
      WAT were not associated to the increase of circulating insulin. Our results show
      that cholecystokinin promotes lipid storage in WAT by acting on adipocyte CCK-2R,
      suggesting a pivotal role for CCK in TG homeostasis.

PMID- 29339380
TI  - Negative regulation of the Keap1-Nrf2 pathway by a p62/Sqstm1 splicing variant.
AB  - A key anti-oxidant pathway, the Keap1-Nrf2 system, is regulated by p62/Sqstm1 via
      multiple mechanisms, including gene expression, post-translational modifications
      such as ubiquitination and phosphorylation, and autophagic degradation of
      p62/Sqstm1 and Keap1. Herein, we demonstrate a novel mode of regulation of the
      Keap1-Nrf2 system, mediated by a splicing variant of p62/Sqstm1 pre-mRNA. Ensembl
      database search and subsequent biochemical analyses in mice revealed the presence
      of an mRNA that encodes p62/Sqstm1 protein lacking the Keap1-interacting region
      (KIR), which is essential for the interaction with Keap1. Like full-length p62,
      the variant was induced under conditions in which Nrf2 was activated (e.g.,
      impairment of autophagy), oligomerized with itself and/or full-length protein,
      and was degraded by autophagy. However, the variant failed to interact with Keap1
      and sequester it into variant-positive aggregates. Remarkably, while full-length
      p62 stabilized Nrf2 and induced the gene expression of Nrf2 targets, the variant
      increased the amount of Keap1 and enhanced ubiquitination of Nrf2, thereby
      suppressing the induction of Nrf2 targets. Hepatocytes isolated from genetically
      modified mice that express full-length p62, but not the variant, were susceptible
      to activation of Nrf2 in response to stress. Collectively, our results suggest
      that splicing of p62/Sqstm1 pre-mRNA negatively regulates the Keap1-Nrf2 pathway.

PMID- 29339382
TI  - In Vitro Susceptibility of Neisseria gonorrhoeae Strains to Mupirocin, an
      Antibiotic Reformulated for Parenteral Administration in Nanoliposomes.
AB  - Neisseria gonorrhoeae is an urgent antibiotic-resistant threat. This study
      determined the MICs of mupirocin to be 0.0039 to 0.0625 MUg/ml for 94 N.
      gonorrhoeae strains. Cross-resistance with other antibiotics was not detected.
      Mupirocin, which is currently limited to topical administration, demonstrated
      activity by injection when delivered in nanoliposomes. The nanoliposomal
      formulation of mupirocin is a potential treatment for drug-resistant N.
      gonorrhoeae.

PMID- 29339383
TI  - New Shuttle Vectors for Gene Cloning and Expression in Multidrug-Resistant
      Acinetobacter Species.
AB  - Understanding bacterial pathogenesis requires adequate genetic tools to assess
      the role of individual virulence determinants by mutagenesis and complementation
      assays, as well as for homologous and heterologous expression of cloned genes.
      Our knowledge of Acinetobacter baumannii pathogenesis has so far been limited by
      the scarcity of genetic tools to manipulate multidrug-resistant (MDR) epidemic
      strains, which are responsible for most infections. Here, we report on the
      construction of new multipurpose shuttle plasmids, namely, pVRL1 and pVRL2, which
      can efficiently replicate in Acinetobacter spp. and in Escherichia coli The pVRL1
      plasmid has been constructed by combining (i) the cryptic plasmid pWH1277 from
      Acinetobacter calcoaceticus, which provides an origin of replication for
      Acinetobacter spp.; (ii) a ColE1-like origin of replication; (iii) the gentamicin
      or zeocin resistance cassette for antibiotic selection; and (iv) a multilinker
      containing several unique restriction sites. Modification of pVRL1 led to the
      generation of the pVRL2 plasmid, which allows arabinose-inducible gene
      transcription with an undetectable basal expression level of cloned genes under
      uninduced conditions and a high dynamic range of responsiveness to the inducer.
      Both pVRL1 and pVRL2 can easily be selected in MDR A. baumannii, have a narrow
      host range and a high copy number, are stably maintained in Acinetobacter spp.,
      and appear to be compatible with indigenous plasmids carried by epidemic strains.
      Plasmid maintenance is guaranteed by the presence of a toxin-antitoxin system,
      providing more insights into the mechanism of plasmid stability in Acinetobacter
      spp.

PMID- 29339384
TI  - A Novel Inhibitor of the LolCDE ABC Transporter Essential for Lipoprotein
      Trafficking in Gram-Negative Bacteria.
AB  - The outer membrane is an essential structural component of Gram-negative bacteria
      that is composed of lipoproteins, lipopolysaccharides, phospholipids, and
      integral beta-barrel membrane proteins. A dedicated machinery, called the Lol
      system, ensures proper trafficking of lipoproteins from the inner to the outer
      membrane. The LolCDE ABC transporter is the inner membrane component, which is
      essential for bacterial viability. Here, we report a novel pyrrolopyrimidinedione
      compound, G0507, which was identified in a phenotypic screen for inhibitors of
      Escherichia coli growth followed by selection of compounds that induced the
      extracytoplasmic sigmaE stress response. Mutations in lolC, lolD, and lolE
      conferred resistance to G0507, suggesting LolCDE as its molecular target.
      Treatment of E. coli cells with G0507 resulted in accumulation of fully processed
      Lpp, an outer membrane lipoprotein, in the inner membrane. Using purified protein
      complexes, we found that G0507 binds to LolCDE and stimulates its ATPase
      activity. G0507 still binds to LolCDE harboring a Q258K substitution in LolC
      (LolCQ258K), which confers high-level resistance to G0507 in vivo but no longer
      stimulates ATPase activity. Our work demonstrates that G0507 has significant
      promise as a chemical probe to dissect lipoprotein trafficking in Gram-negative
      bacteria.

PMID- 29339385
TI  - A Before-and-After Study of the Effectiveness of an Antimicrobial Stewardship
      Program in Critical Care.
AB  - We evaluated the use of antimicrobials expressed as defined daily doses (DDDs)
      per 1,000 patient days and days of therapy (DOT) per 100 occupied bed-days in a
      intensive care unit (ICU) of a general hospital in Barcelona, Spain, before and
      after implementation of an antimicrobial stewardship (AMS) program (2007 to 2010
      versus 2011 to 2015). The quarterly costs of antimicrobials used in the ICU and
      its weight in the overall hospital costs of antimicrobials were calculated. The
      effect of the applied AMS program on DDDs and DOT time series data was analyzed
      by means of intervention time series analysis. A total of 5,002 patients were
      included (1,971 for the first [before] period and 3,031 for the second [after]
      period). The percentage of patients treated with one or more antimicrobials
      decreased from 88.6 to 77.2% (P < 0.001). DDDs decreased from 246.8 to 192.3
      (mean difference, -54.5; P = 0.001) and DOT from 66.7 to 54.6 (mean difference, 
      12.1; P = 0.066). The mean cost per trimester decreased from ?115,543 to ?73,477
      (mean difference, -42,065.4 euros; P < 0.001), and the percentage of ICU
      antimicrobials cost with respect to the total cost of hospital antimicrobials
      decreased from 28.5 to 22.8% (mean difference, -5.59; P = 0.023). Implementation
      of an AMS program in the ICU was associated with a marked reduction in the use of
      antimicrobials, with cost savings close to one million euros since its
      implementation. An AMS program can have a significant impact on optimizing
      antimicrobial use in critical care practice.

PMID- 29339386
TI  - Pterostilbene, a Potential MCR-1 Inhibitor That Enhances the Efficacy of
      Polymyxin B.
AB  - We characterized the synergistic effect produced between pterostilbene and
      polymyxin B (fractional inhibitory concentration [FIC] index = 0.156 or 0.188)
      against MCR-producing Escherichia coli strains of both human and animal origins.
      The time-killing assays showed that either pterostilbene or polymyxin B failed to
      eradicate the mcr-1- and NDM-positive E. coli strain ZJ487, but the combination
      eliminated the strain by 1 h postinoculation. The survival rate of mice after
      intraperitoneal infections was significantly enhanced from 0% to 60% in the group
      in which combination therapy was applied.

PMID- 29339387
TI  - Genetic Basis of Emerging Vancomycin, Linezolid, and Daptomycin Heteroresistance
      in a Case of Persistent Enterococcus faecium Bacteremia.
AB  - Whole-genome sequencing was used to examine a persistent Enterococcus faecium
      bacteremia that acquired heteroresistance to three antibiotics in response to
      prolonged multidrug therapy. A comparison of the complete genomes before and
      after each change revealed the emergence of known resistance determinants for
      vancomycin and linezolid and suggested that a novel mutation in fabF, encoding a
      fatty acid synthase, was responsible for daptomycin nonsusceptibility. Plasmid
      recombination contributed to the progressive loss of vancomycin resistance after
      withdrawal of the drug.

PMID- 29339388
TI  - Combating Carbapenem-Resistant Acinetobacter baumannii by an Optimized Imipenem
      plus-Tobramycin Dosage Regimen: Prospective Validation via Hollow-Fiber Infection
      and Mathematical Modeling.
AB  - We aimed to prospectively validate an optimized combination dosage regimen
      against a clinical carbapenem-resistant Acinetobacter baumannii (CRAB) isolate
      (imipenem MIC, 32 mg/liter; tobramycin MIC, 2 mg/liter). Imipenem at constant
      concentrations (7.6, 13.4, and 23.3 mg/liter, reflecting a range of clearances)
      was simulated in a 7-day hollow-fiber infection model (inoculum, ~107.2 CFU/ml)
      with and without tobramycin (7 mg/kg q24h, 0.5-h infusions). While monotherapies
      achieved no killing or failed by 24 h, this rationally optimized combination
      achieved >5 log10 bacterial killing and suppressed resistance.

PMID- 29339389
TI  - In Vitro Antibiotic Susceptibility Pattern of Non-diphtheriae Corynebacterium
      Isolates in Ontario, Canada, from 2011 to 2016.
AB  - Non-diphtheriae Corynebacterium-associated disease has been increasingly observed
      and often presents a conundrum to the treating physician. Analysis of antibiotic
      susceptibility testing data for 1,970 clinical Corynebacterium isolates received
      between 2011 and 2016 revealed that empirical drug treatment options are limited
      to vancomycin and linezolid. Corynebacterium striatum was the most frequently
      observed species during this study period, along with C. amycolatum and C.
      pseudodiphtheriticum/C. propinquum Low levels of susceptibility to penicillin
      (14.5%), erythromycin (15.1%), and clindamycin (8.7%) were observed for non
      diphtheriae Corynebacterium species, while 3.0% of isolates were not susceptible
      to daptomycin. Similarly, 26.9% and 38.1% of Corynebacterium isolates were
      susceptible to ciprofloxacin and trimethoprim-sulfamethoxazole, respectively. Our
      data show much lower susceptibility to penicillin than previously reported in the
      literature and an increasing number of isolates resistant to daptomycin,
      highlighting the need for continued antibiotic surveillance studies for
      appropriate patient management and treatment success.

PMID- 29339391
TI  - Intrapulmonary Pharmacokinetics of Lascufloxacin in Healthy Adult Volunteers.
AB  - This study was performed to investigate the intrapulmonary penetration of
      lascufloxacin in humans. Thirty healthy adult male Japanese subjects, allocated
      into five groups, received lascufloxacin in a single oral dose of 75 mg.
      Bronchoalveolar lavage and blood sampling were performed simultaneously in each
      subject at 1, 2, 4, 6, or 24 h after administration, and lascufloxacin
      concentrations in plasma, epithelial lining fluid, and alveolar macrophages were
      determined. Lascufloxacin was rapidly distributed to the epithelial lining fluid
      with a time to maximum drug concentration (Tmax) of 1 h, which was identical to
      that in plasma. The maximum concentration of drug (Cmax) values in plasma,
      epithelial lining fluid, and alveolar macrophages were 0.576, 12.3, and 21.8
      MUg/ml, respectively. The corresponding area under the concentration-time curve
      from 0 to 24 h (AUC0-24) values were 7.67, 123, and 325 MUg . h/ml. The mean drug
      concentrations in the epithelial lining fluid and alveolar macrophages were much
      higher than those in plasma at all time points examined, and the average site-to
      free plasma concentration ratios fell within the ranges of 57.5 to 86.4 and 71.0
      to 217, respectively. Drug levels in epithelial lining fluid and alveolar
      macrophages exceeded the MIC90 values for common respiratory pathogens. (This
      study was registered at JAPIC under registration number JapicCTI-142547.).

PMID- 29339390
TI  - Identification of Hsp90 Inhibitors with Anti-Plasmodium Activity.
AB  - Malaria remains a global health burden partly due to Plasmodium parasite
      resistance to first-line therapeutics. The molecular chaperone heat shock protein
      90 (Hsp90) has emerged as an essential protein for blood-stage Plasmodium
      parasites, but details about its function during malaria's elusive liver stage
      are unclear. We used target-based screens to identify compounds that bind to
      Plasmodium falciparum and human Hsp90, which revealed insights into chemotypes
      with species-selective binding. Using cell-based malaria assays, we demonstrate
      that all identified Hsp90-binding compounds are liver- and blood-stage Plasmodium
      inhibitors. Additionally, the Hsp90 inhibitor SNX-0723 in combination with the
      phosphatidylinositol 3-kinase inhibitor PIK-75 synergistically reduces the liver
      stage parasite load. Time course inhibition studies with the Hsp90 inhibitors and
      expression analysis support a role for Plasmodium Hsp90 in late-liver-stage
      parasite development. Our results suggest that Plasmodium Hsp90 is essential to
      liver- and blood-stage parasite infections and highlight an attractive route for
      development of species-selective PfHsp90 inhibitors that may act synergistically
      in combination therapies to prevent and treat malaria.

PMID- 29339392
TI  - A Novel Piperazine-Based Drug Lead for Cryptosporidiosis from the Medicines for
      Malaria Venture Open-Access Malaria Box.
AB  - Cryptosporidiosis causes life-threatening diarrhea in children under the age of 5
      years and prolonged diarrhea in immunodeficient people, especially AIDS patients.
      The standard of care, nitazoxanide, is modestly effective in children and
      ineffective in immunocompromised individuals. In addition to the need for new
      drugs, better knowledge of drug properties that drive in vivo efficacy is needed
      to facilitate drug development. We report the identification of a piperazine
      based lead compound for Cryptosporidium drug development, MMV665917, and a new
      pharmacodynamic method used for its characterization. The identification of
      MMV665917 from the Medicines for Malaria Venture Malaria Box was followed by dose
      response studies, in vitro toxicity studies, and structure-activity relationship
      studies using commercial analogues. The potency of this compound against
      Cryptosporidium parvum Iowa and field isolates was comparable to that against
      Cryptosporidium hominis Furthermore, unlike nitazoxanide, clofazimine, and
      paromomycin, MMV665917 appeared to be curative in a NOD SCID gamma mouse model of
      chronic cryptosporidiosis. MMV665917 was also efficacious in a gamma interferon
      knockout mouse model of acute cryptosporidiosis. To determine if efficacy in this
      mouse model of chronic infection might relate to whether compounds are
      parasiticidal or parasitistatic for C. parvum, we developed a novel in vitro
      parasite persistence assay. This assay suggested that MMV665917 was
      parasiticidal, unlike nitazoxanide, clofazimine, and paromomycin. The assay also
      enabled determination of the concentration of the compound required to maximize
      the rate of parasite elimination. This time-kill assay can be used to prioritize
      early-stage Cryptosporidium drug leads and may aid in planning in vivo efficacy
      experiments. Collectively, these results identify MMV665917 as a promising lead
      and establish a new method for characterizing potential anticryptosporidial
      agents.

PMID- 29339393
TI  - Early Clinical Assessment of the Antimicrobial Activity of Finafloxacin Compared
      to Ciprofloxacin in Subsets of Microbiologically Characterized Isolates.
AB  - Two phase II studies were performed with patients with uncomplicated urinary
      tract infections (uUTIs) and complicated urinary tract infections (cUTIs) or
      acute pyelonephritis (PN) to compare finafloxacin (300 mg twice a day [b.i.d.]
      orally for uUTI and 800 mg once a day [q.d.] intravenously [i.v.] for cUTI/PN)
      and ciprofloxacin (250 mg b.i.d. orally for uUTI and 400 mg b.i.d. i.v. for
      cUTI/PN). The early response to the study medications was evaluated in the
      microbiological intent-to-treat population (mITT) at day 3. A total of 21% of the
      isolates were ciprofloxacin resistant, 13.7% were primed pathogens carrying a
      mutation(s) potentially fostering fluoroquinolone resistance development, and
      7.1% produced extended-spectrum beta-lactamases (ESBLs). Finafloxacin
      demonstrated very good early clinical activity, with microbiological eradication
      rates of 88.6% (n = 132), compared to 78.7% (n = 61) for ciprofloxacin, and 69.6%
      (n = 23), compared to 35.7% (n = 14) for ciprofloxacin, in patients with
      ciprofloxacin-resistant uropathogens; 94.1% (n = 17), compared to 80.0% (n = 10)
      for ciprofloxacin, in patients infected with uropathogens primed for
      fluoroquinolone resistance uropathogens; and 91.7% (n = 11), compared to 0% for
      ciprofloxacin, in patients infected with ESBL producers. Finafloxacin
      demonstrated early and rapid activity against uropathogens, including
      fluoroquinolone-resistant and/or multiresistant pathogens or ESBL producers,
      while ciprofloxacin was less active against this subset of resistant pathogens.
      Susceptibilities of pathogens were quantitated by broth microdilution. Isolates
      were subgrouped according to their susceptibility patterns, in particular first
      step quinolone resistance, quinolone resistance, and ESBL production. Eradication
      was defined as the elimination or reduction of study entry pathogens to <103
      CFU/ml in urine culture. (The studies described in this paper have been
      registered at ClinicalTrials.gov under identifiers NCT00722735 and NCT01928433.).

PMID- 29339394
TI  - Population Pharmacokinetics of Finafloxacin in Healthy Volunteers and Patients
      with Complicated Urinary Tract Infections.
AB  - Finafloxacin is a novel fluoroquinolone with increased antibacterial activity at
      acidic pH and reduced susceptibility to several resistance mechanisms. A phase II
      study revealed a good efficacy/safety profile in patients with complicated
      urinary tract infections (cUTIs), while the pharmacokinetics was characterized by
      highly variable concentration-versus-time profiles, suggesting the need for an
      elaborated pharmacokinetic model. Data from three clinical trials were evaluated:
      127 healthy volunteers were dosed orally (n = 77) or intravenously (n = 50), and
      139 patients with cUTI received finafloxacin intravenously. Plasma (2,824 samples
      from volunteers and 414 samples from patients) and urine (496 samples from
      volunteers and 135 samples patients) concentrations were quantified by liquid
      chromatography-tandem mass spectrometry (LC-MS/MS). NONMEM was used to build a
      population pharmacokinetic model, and pharmacokinetic/pharmacodynamic
      relationships were investigated via simulations and logistic regression. A two
      compartment model with first-order elimination described the data best (central
      volume of distribution [Vc] and peripheral volume of distribution [Vp] of 47
      liters [20%] and 43 liters [67%], respectively, and elimination clearance and
      intercompartmental clearance of 21 liters/h [54%] and 2.8 liters/h [57%],
      respectively [median bootstrap estimates {coefficients of variation}]). Vc
      increased with body surface area, and clearance was reduced in patients (-29%).
      Oral absorption was described best by parallel first- and zero-order processes
      (bioavailability of 75%). No pharmacodynamic surrogate parameter of
      clinical/microbiological outcome could be identified, which depended exclusively
      on the MIC of the causative pathogens. Despite the interindividual variability,
      the present data set does not support covariate-based dose adjustments. Based on
      the favorable safety and efficacy data, the clinical relevance of the observed
      variability appears to be limited. (This study has been registered at
      ClinicalTrials.gov under identifier NCT01928433.).

PMID- 29339395
TI  - Explorative Randomized Phase II Clinical Study of the Efficacy and Safety of
      Finafloxacin versus Ciprofloxacin for Treatment of Complicated Urinary Tract
      Infections.
AB  - The broad-spectrum C-8-cyano-fluoroquinolone finafloxacin displays enhanced
      activity under acidic conditions. This phase II clinical study compared the
      efficacies and safeties of finafloxacin and ciprofloxacin in patients with
      complicated urinary tract infection and/or pyelonephritis. A 5-day regimen with
      800 mg finafloxacin once a day (q.d.) (FINA05) had results similar to those of a
      10-day regimen with 800 mg finafloxacin q.d. (FINA10). Combined microbiological
      and clinical responses at the test-of-cure (TOC) visit were 70% for FINA05, 68%
      for FINA10, and 57% for a 10-day ciprofloxacin regimen (CIPRO10) in 193 patients
      (64 for FINA05, 68 for FINA10, and 61 for CIPRO10) of the microbiological intent
      to-treat (mITT) population. Additionally, the clinical effects of ciprofloxacin
      on patients with an acidic urine pH (80% of patients) were reduced, whereas the
      effects of finafloxacin were unchanged. Finafloxacin was safe and well tolerated.
      Overall, 43.4% of the patients in the FINA05 group, 42.7% in the FINA10 group,
      and 54.2% in the CIPRO10 group experienced mostly mild and treatment-emergent but
      unrelated adverse events. A short-course regimen of 5 days of finafloxacin
      resulted in high eradication and improved clinical outcome rates compared to
      those for treatment with ciprofloxacin for 10 days. In contrast to those of
      ciprofloxacin, the clinical effects of finafloxacin were not reduced by acidic
      urine pH. Hospitalized adults were randomized 1:1:1 to finafloxacin treatment
      (800 mg q.d.) for either 5 or 10 days or to ciprofloxacin treatment (400 mg/500
      mg b.i.d.) for 10 days with an optional switch from intravenous (i.v.) to oral
      administration at day 3. The primary endpoint was the combined microbiological
      and clinical response at the TOC visit in the microbiological intent-to-treat
      population. (This study has been registered at ClinicalTrials.gov under
      identifier NCT01928433.).

PMID- 29339396
TI  - Efficacy of Apramycin against Multidrug-Resistant Acinetobacter baumannii in the
      Murine Neutropenic Thigh Model.
AB  - Apramycin, an aminocyclitol aminoglycoside, was rapidly bactericidal against
      Acinetobacter baumannii In a neutropenic murine thigh infection model, treatment
      associated A. baumannii CFU reductions of >4 log10 per thigh were observed for
      all exposures for which area under the curve (AUC)/MIC ratio was >50 and maximum
      concentration of drug in serum (Cmax)/MIC was ~10 or higher. Based on these
      findings, we suggest that apramycin deserves further preclinical exploration as a
      repurposed therapeutic for multidrug-resistant Gram-negative pathogens, including
      A. baumannii.

PMID- 29339398
TI  - Assay Conditions Influence Affinities of Rat Organic Cation Transporter 1:
      Analysis of Mutagenesis in the Modeled Outward-Facing Cleft by Measuring Effects
      of Substrates and Inhibitors on Initial Uptake.
AB  - The effects of mutations in the modeled outward-open cleft of rat organic cation
      transporter 1 (rOCT1) on affinities of substrates and inhibitors were
      investigated. Human embryonic kidney 293 cells were stably transfected with rOCT1
      or rOCT1 mutants, and uptake of the substrates 1-methyl-4-phenylpyridinium+
      (MPP+) and tetraethylammonium+ (TEA+) or inhibition of MPP+ uptake by the
      nontransported inhibitors tetrabutylammonium+ (TBuA+), tetrapentylammonium+
      (TPeA+), and corticosterone was measured. Uptake measurements were performed on
      confluent cell layers using a 2-minute incubation or in dissociated cells using
      incubation times of 1, 5, or 10 seconds. With both methods, different apparent
      Michaelis-Menten constant (Km) values, different IC50 values, and varying effects
      of mutations were determined. In addition, varying IC50 values for the inhibition
      of MPP+ uptake and varying effects of mutations were obtained when different MPP+
      concentrations far below the apparent Km value were used for uptake measurements.
      Eleven mutations were investigated by measuring initial uptake in dissociated
      cells and employing 0.1 uM MPP+ for uptake during inhibition experiments. Altered
      affinities for substrates and/or inhibitors were observed when Phe160, Trp218,
      Arg440, Leu447, and Asp475 were mutated. The mutations resulted in changes of
      apparent Km values for TEA+ and/or MPP+ Mutation of Trp218 and Asp475 led to
      altered IC50 values for TBuA+, TPeA+, and corticosterone, whereas the mutation of
      Phe160 and Leu447 changed the IC50 values for two inhibitors. Thereby amino acids
      in the outward-facing conformation of rOCT1 could be identified that interact
      with structurally different inhibitors and probably also with different
      substrates.

PMID- 29339397
TI  - Heat Shock Factor HsfA1a Is Essential for R Gene-Mediated Nematode Resistance and
      Triggers H2O2 Production1.
AB  - Plants generate reactive oxygen species (ROS) in the apoplast in response to
      pathogen attack, especially following resistance (R) gene-mediated pathogen
      recognition; however, the mechanisms activating ROS generation remain unknown.
      Here, we demonstrate that RKN (Meloidogyne incognita) infection rapidly induces
      ROS accumulation in the roots of tomato (Solanum lycopersicum) plants that
      contain the R gene Mi-1.2 but rarely induces ROS accumulation in the susceptible
      or Mi-1.2-silenced resistant genotypes. RNK also induces the hypersensitive
      response, a form of programmed cell death, in Mi-1.2 plants. RKN induces the
      expression of numerous class-A heat shock factor (HsfA) genes in resistant tomato
      plants. Silencing HsfA1a compromises Mi-1.2-mediated resistance, apoplastic H2O2
      accumulation, and the transcription of whitefly induced 1 (Wfi1), which encodes a
      respiratory burst oxidase homolog. HsfA1a regulates Wfi1 transcription by binding
      to the Wfi1 promoter, and silencing of Wfi1 compromises Mi-1.2-mediated
      resistance. HsfA1a and Wfi1 are involved in Mi-1.2-triggered Hsp90 accumulation
      and basal defense in susceptible tomato. Thus, HsfA-1aWfi1-dependent ROS
      signaling functions as a crucial regulator of plant defense responses.

PMID- 29339399
TI  - Ovariectomy-induced bone loss in TNFalpha and IL6 gene knockout mice is regulated
      by different mechanisms.
AB  - We examined the effects of tumor necrosis factor-alpha (TNFalpha) and interleukin
      6 (IL6) gene knockout in preserving the bone loss induced by ovariectomy (OVX)
      and the mechanisms involved in bone metabolism. Twenty female wild-type (WT),
      TNFalpha-knockout (TNFalpha-/-) or IL6-knockout (IL6-/-) mice aged 12 weeks were
      sham-operated (SHAM) or subjected to OVX and killed after 4 weeks. Bone mass and
      skeletal microarchitecture were determined using micro-CT. Bone marrow stromal
      cells (BMSCs) from all three groups (WT, TNFalpha-/- and IL6-/-) were induced to
      differentiate into osteoblasts or osteoclasts and treated with 17-beta-estradiol.
      Bone metabolism was assessed by histological analysis, serum analyses and qRT
      PCR. OVX successfully induced a high turnover in all mice, but a repair effect
      was observed in TNFalpha-/- and IL6-/- mice. The ratio of femoral trabecular bone
      volume to tissue volume, trabecular number and trabecular thickness were
      significantly decreased in WT mice subjected to OVX, but increased in TNFalpha-/-
      mice (1.62, 1.34, 0.27-fold respectively; P < 0.01) and IL6-/- mice (1.34, 0.80,
      0.22-fold respectively; P < 0.01). Furthermore, we observed a 29.6% increase in
      the trabecular number in TNFalpha-/- mice when compared to the IL6-/- mice. Both,
      TNFalpha-/- and IL6-/- BMSCs exhibited decreased numbers of TRAP-positive cells
      and an increase in ALP-positive cells, with or without E2 treatment (P < 0.05).
      While the knockout of TNFalpha or IL6 significantly upregulated mRNA expressions
      of osteoblast-related genes (Runx2 and Col1a1) and downregulated osteoclast
      related mRNA for TRAP, MMP9 and CTSK in vivo and in vitro, TNFalpha knockout
      appeared to have roles beyond IL6 knockout in upregulating Col1a1 mRNA expression
      and downregulating mRNA expressions of WNT-related genes (DKK1 and Sost) and TNF
      related activation-induced genes (TRAF6). TNFalpha seemed to be more potentially
      invasive in inhibiting bone formation and enhancing TRAF6-mediated
      osteoclastogenesis than IL6, implying that the regulatory mechanisms of TNFalpha
      and IL6 in bone metabolism may be different.

PMID- 29339400
TI  - Intact glucose uptake despite deteriorating signaling in adipocytes with high-fat
      feeding.
AB  - To capture immediate cellular changes during diet-induced expansion of adipocyte
      cell volume and number, we characterized mature adipocytes during a short-term
      high-fat diet (HFD) intervention. Male C57BL6/J mice were fed chow diet, and then
      switched to HFD for 2, 4, 6 or 14 days. Systemic glucose clearance was assessed
      by glucose tolerance test. Adipose tissue was dissected for RNA-seq and cell size
      distribution analysis using coulter counting. Insulin response in isolated
      adipocytes was monitored by glucose uptake assay and Western blotting, and
      confocal microscopy was used to assess autophagic activity. Switching to HFD was
      accompanied by an immediate adipocyte size expansion and onset of systemic
      insulin resistance already after two days, followed by recruitment of new
      adipocytes. Despite an initially increased non-stimulated and preserved insulin
      stimulated glucose uptake, we observed a decreased phosphorylation of insulin
      receptor substrate-1 (IRS-1) and protein kinase B (PKB). After 14 days of HFD,
      both the insulin-stimulated phosphorylation of Akt substrate of 160 kDa (AS160)
      and glucose uptake was blunted. RNA-seq analysis of adipose tissue revealed
      transient changes in gene expression at day four, including highly significant
      upregulation of Trp53inp, previously demonstrated to be involved in autophagy. We
      confirmed increased autophagy, measured as an increased density of LC3-positive
      puncta and decreased p62 expression after 14 days of HFD. In conclusion, HFD
      rapidly induced systemic insulin resistance, whereas insulin-stimulated glucose
      uptake remained intact throughout 6 days of HFD feeding. We also identified
      autophagy as an early cellular process that potentially influences adipocyte
      function upon switching to HFD.

PMID- 29339401
TI  - The impact of preload reduction with head-up tilt testing on longitudinal and
      transverse left ventricular mechanics: a study utilizing deformation volume
      analysis.
AB  - BACKGROUND: Left ventricular (LV) function is dependent on load, intrinsic
      contractility and relaxation with a variable impact on specific mechanics. Strain
      (epsilon) imaging allows the assessment of cardiac function; however, the direct
      relationship between volume and strain is currently unknown. The aim of this
      study was to establish the impact of preload reduction through head-up tilt (HUT)
      testing on simultaneous left ventricular (LV) longitudinal and transverse
      function and their respective contribution to volume change. METHODS: A focused
      transthoracic echocardiogram was performed on 10 healthy male participants (23 +/
      3 years) in the supine position and following 1 min and 5 min of HUT testing.
      Raw temporal longitudinal epsilon (Ls) and transverse epsilon (Ts) values were
      exported and divided into 5% increments across the cardiac cycle and
      corresponding LV volumes were traced at each 5% increment. This provided
      simultaneous LV longitudinal and transverse epsilon and volume loops (deformation
      volume analysis - DVA). RESULTS: There was a leftward shift of the epsilon-volume
      loop from supine to 1 min and 5 min of HUT (P < 0.001). Moreover, longitudinal
      shortening was reduced (P < 0.001) with a concomitant increase in transverse
      thickening from supine to 1 min, which was further augmented at 5 min (P =
      0.018). CONCLUSIONS: Preload reduction occurs within 1 min of HUT but does not
      further reduce at 5 min. This decline is associated with a decrease in
      longitudinal epsilon and concomitant increase in transverse epsilon.
      Consequently, augmented transverse relaxation appears to be an important factor
      in the maintenance of LV filling in the setting of reduced preload. DVA provides
      information on the relative contribution of mechanics to a change in LV volume
      and may have a role in the assessment of clinical populations.

PMID- 29339402
TI  - Canonical Notch signaling is dispensable for adult steady-state and stress myelo
      erythropoiesis.
AB  - Although an essential role for canonical Notch signaling in generation of
      hematopoietic stem cells in the embryo and in thymic T-cell development is well
      established, its role in adult bone marrow (BM) myelopoiesis remains unclear.
      Some studies, analyzing myeloid progenitors in adult mice with inhibited Notch
      signaling, implicated distinct roles of canonical Notch signaling in regulation
      of progenitors for the megakaryocyte, erythroid, and granulocyte-macrophage cell
      lineages. However, these studies might also have targeted other pathways.
      Therefore, we specifically deleted, in adult BM, the transcription factor
      recombination signal-binding protein J kappa (Rbpj), through which canonical
      signaling from all Notch receptors converges. Notably, detailed progenitor
      staging established that canonical Notch signaling is fully dispensable for all
      investigated stages of megakaryocyte, erythroid, and myeloid progenitors in
      steady state unperturbed hematopoiesis, after competitive BM transplantation, and
      in stress-induced erythropoiesis. Moreover, expression of key regulators of these
      hematopoietic lineages and Notch target genes were unaffected by Rbpj deficiency
      in BM progenitor cells.

PMID- 29339403
TI  - A phase 1 study of azacitidine combined with chemotherapy in childhood leukemia:
      a report from the TACL consortium.

PMID- 29339404
TI  - Hif-1alpha and Hif-2alpha regulate hemogenic endothelium and hematopoietic stem
      cell formation in zebrafish.
AB  - During development, hematopoietic stem cells (HSCs) derive from specialized
      endothelial cells (ECs) called hemogenic endothelium (HE) via a process called
      endothelial-to-hematopoietic transition (EHT). Hypoxia-inducible factor-1alpha
      (HIF-1alpha) has been reported to positively modulate EHT in vivo, but current
      data indicate the existence of other regulators of this process. Here we show
      that in zebrafish, Hif-2alpha also positively modulates HSC formation.
      Specifically, HSC marker gene expression is strongly decreased in hif-1aa;hif-1ab
      (hif-1alpha) and in hif-2aa;hif-2ab (hif-2alpha) zebrafish mutants and morphants.
      Moreover, live imaging studies reveal a positive role for hif-1alpha and hif
      2alpha in regulating HE specification. Knockdown of hif-2alpha in hif-1alpha
      mutants leads to a greater decrease in HSC formation, indicating that hif-1alpha
      and hif-2alpha have partially overlapping roles in EHT. Furthermore, hypoxic
      conditions, which strongly stimulate HSC formation in wild-type animals, have
      little effect in the combined absence of Hif-1alpha and Hif-2alpha function. In
      addition, we present evidence for Hif and Notch working in the same pathway
      upstream of EHT. Both notch1a and notch1b mutants display impaired EHT, which
      cannot be rescued by hypoxia. However, overexpression of the Notch intracellular
      domain in ECs is sufficient to rescue the hif-1alpha and hif-2alpha morphant EHT
      phenotype, suggesting that Notch signaling functions downstream of the Hif
      pathway during HSC formation. Altogether, our data provide genetic evidence that
      both Hif-1alpha and Hif-2alpha regulate EHT upstream of Notch signaling.

PMID- 29339405
TI  - Health care professionals' neckties as a source of transmission of bacteria to
      patients: a systematic review.
AB  - BACKGROUND: There is growing concern that neckties worn by health care
      professionals may contribute to infections contracted in health care settings. We
      evaluated the evidence for health-care-associated infections resulting from
      neckties and whether the evidence is sufficient to warrant a tieless policy in
      Canada. METHODS: We performed a systematic review to determine whether neckties
      worn by health care professionals colonize harmful pathogenic bacteria and
      whether they contribute to the spread of infection to patients in the inpatient
      or outpatient setting. We searched PubMed (1966 to 2017) and Embase (1974 to
      2017). The level of evidence was appraised according to the Oxford Centre for
      Evidence-Based Medicine levels of evidence. We evaluated the quality of evidence
      and the risk of bias using the Jadad scale or the Newcastle-Ottawa Scale.
      RESULTS: We screened 1675 citations, of which 6 were ultimately included in the
      systematic review. Only 1 study gave level 1b evidence (randomized controlled
      trial). Neckties were more likely than shirt pockets to colonize bacteria. There
      is limited evidence that neckties may be contaminated with pathogenic bacteria
      (e.g., methicillin-resistant Staphylococcus aureus) and very limited evidence
      that contaminated neckties may transmit bacteria (in a controlled experimental
      setting to a mannequin). INTERPRETATION: There is no evidence of increased rates
      of health-care-associated infections related to the wearing of neckties by health
      care professionals. There is weak evidence that neckties are contaminated with
      pathogenic (and nonpathogenic) bacteria. The level of evidence was weak and the
      studies were heterogeneous. Evidence to support the need for a tieless dress code
      policy is lacking.

PMID- 29339406
TI  - Genetic Diversity, Molecular Phylogeny, and Selection Evidence of Jinchuan Yak
      Revealed by Whole-Genome Resequencing.
AB  - Jinchuan yak, a newly discovered yak breed, not only possesses a large proportion
      of multi-ribs but also exhibits many good characteristics, such as high meat
      production, milk yield, and reproductive performance. However, there is limited
      information about its overall genetic structure, relationship with yaks in other
      areas, and possible origins and evolutionary processes. In this study, 7,693,689
      high-quality single-nucleotide polymorphisms were identified by resequencing the
      genome of Jinchuan yak. Principal component and population genetic structure
      analyses showed that Jinchuan yak could be distinguished as an independent
      population among the domestic yak population. Linkage disequilibrium analysis
      showed that the decay rate of Jinchuan yak was the lowest of the domestic yak
      breeds, indicating that the degree of domestication and selection intensity of
      Jinchuan yak were higher than those of other yak breeds. Combined with
      archaeological data, we speculated that the origin of domestication of Jinchuan
      yak was ~6000 yr ago (4000-10,000 yr ago). The quantitative dynamics of
      population growth history in Jinchuan yak was similar to that of other breeds of
      domestic and wild yaks, but was closer to that of the wild yak. No significant
      gene exchange between Jinchuan and other domestic yaks occurred. Compared with
      other domestic yaks, Jinchuan yak possessed 339 significantly and positively
      selected genes, several of which relate to physiological rhythm, histones, and
      the breed's excellent production characteristics. Our results provide a basis for
      the discovery of the evolution, molecular origin, and unique traits of Jinchuan
      yak.

PMID- 29339407
TI  - Genomic Identification and Functional Characterization of Essential Genes in
      Caenorhabditis elegans.
AB  - Using combined genetic mapping, Illumina sequencing, bioinformatics analyses, and
      experimental validation, we identified 60 essential genes from 104 lethal
      mutations in two genomic regions of Caenorhabditis elegans totaling ~14 Mb on
      chromosome III(mid) and chromosome V(left). Five of the 60 genes had not
      previously been shown to have lethal phenotypes by RNA interference depletion. By
      analyzing the regions around the lethal missense mutations, we identified four
      putative new protein functional domains. Furthermore, functional characterization
      of the identified essential genes shows that most are enzymes, including
      helicases, tRNA synthetases, and kinases in addition to ribosomal proteins. Gene
      Ontology analysis indicated that essential genes often encode for enzymes that
      conduct nucleic acid binding activities during fundamental processes, such as
      intracellular DNA replication, transcription, and translation. Analysis of
      essential gene shows that they have fewer paralogs, encode proteins that are in
      protein interaction hubs, and are highly expressed relative to nonessential
      genes. All these essential gene traits in C. elegans are consistent with those of
      human disease genes. Most human orthologs (90%) of the essential genes in this
      study are related to human diseases. Therefore, functional characterization of
      essential genes underlines their importance as proxies for understanding the
      biological functions of human disease genes.

PMID- 29339408
TI  - Development of the Swimbladder Surfactant System and Biogenesis of Lysosome
      Related Organelles Is Regulated by BLOS1 in Zebrafish.
AB  - Hermansky-Pudlak syndrome (HPS) is a human autosomal recessive disorder that is
      characterized by oculocutaneous albinism and a deficiency of the platelet storage
      pool resulting from defective biogenesis of lysosome-related organelles (LROs).
      To date, 10 HPS genes have been identified, three of which belong to the octamer
      complex BLOC-1 (biogenesis of lysosome-related organelles complex 1). One subunit
      of the BLOC-1 complex, BLOS1, also participates in the BLOC-1-related complex
      (BORC). Due to lethality at the early embryo stage in BLOS1 knockout mice, the
      function of BLOS1 in the above two complexes and whether it has a novel function
      are unclear. Here, we generated three zebrafish mutant lines with a BLOC-1
      deficiency, in which melanin and silver pigment formation was attenuated as a
      result of mutation of bloc1s1, bloc1s2, and dtnbp1a, suggesting that they
      function in the same complex. In addition, mutations of bloc1s1 and bloc1s2
      caused an accumulation of clusters of lysosomal vesicles at the posterior part of
      the tectum, representing a BORC-specific function in zebrafish. Moreover, bloc1s1
      is highly expressed in the swimbladder during postembryonic stages and is
      required for positively regulating the expression of the genes, which is known to
      govern surfactant production and lung development in mammals. Our study
      identified BLOS1 as a crucial regulator of the surfactant system. Thus, the
      zebrafish swimbladder might be an easy system to screen and study genetic
      modifiers that control surfactant production and homeostasis.

PMID- 29339409
TI  - Impact of Homologous Recombination on Silent Chromatin in Saccharomyces
      cerevisiae.
AB  - Specialized chromatin domains repress transcription of genes within them and
      present a barrier to many DNA-protein interactions. Silent chromatin in the
      budding yeast Saccharomyces cerevisiae, akin to heterochromatin of metazoans and
      plants, inhibits transcription of PolII- and PolIII-transcribed genes, yet
      somehow grants access to proteins necessary for DNA transactions like replication
      and homologous recombination. In this study, we adapted a novel assay to detect
      even transient changes in the dynamics of transcriptional silencing at HML after
      it served as a template for homologous recombination. Homologous recombination
      specifically targeted to HML via double-strand-break formation at a homologous
      locus often led to transient loss of transcriptional silencing at HML
      Interestingly, many cells could template homology-directed repair at HML without
      an obligate loss of silencing, even in recombination events with extensive gene
      conversion tracts. In a population of cells that experienced silencing loss
      following recombination, transcription persisted for 2-3 hr after all double
      strand breaks were repaired. mRNA levels from cells that experienced
      recombination-induced silencing loss did not approach the amount of mRNA seen in
      cells lacking transcriptional silencing. Thus, silencing loss at HML after
      homologous recombination was short-lived and limited.

PMID- 29339410
TI  - Maintenance of Genome Integrity by Mi2 Homologs CHD-3 and LET-418 in
      Caenorhabditis elegans.
AB  - Meiotic recombination depends upon the tightly coordinated regulation of
      chromosome dynamics and is essential for the production of haploid gametes.
      Central to this process is the formation and repair of meiotic double-stranded
      breaks (DSBs), which must take place within the constraints of a specialized
      chromatin architecture. Here, we demonstrate a role for the nucleosome remodeling
      and deacetylase (NuRD) complex in orchestrating meiotic chromosome dynamics in
      Caenorhabditis elegans Our data reveal that the conserved Mi2 homologs
      Chromodomain helicase DNA-binding protein (CHD-3) and its paralog LET-418
      facilitate meiotic progression by ensuring faithful repair of DSBs through
      homologous recombination. We discovered that loss of either CHD-3 or LET-418
      results in elevated p53-dependent germ line apoptosis, which relies on the
      activation of the conserved checkpoint kinase CHK-1 Consistent with these
      findings, chd-3 and let-418 mutants produce a reduced number of offspring,
      indicating a role for Mi2 in forming viable gametes. When Mi2 function is
      compromised, persisting recombination intermediates are detected in late
      pachytene nuclei, indicating a failure in the timely repair of DSBs.
      Intriguingly, our data indicate that in Mi2 mutant germ lines, a subset of DSBs
      are repaired by nonhomologous end joining, which manifests as chromosomal
      fusions. We find that meiotic defects are exacerbated in Mi2 mutants lacking CKU
      80, as evidenced by increased recombination intermediates, corpses, and defects
      in chromosomal integrity. Taken together, our findings support a model wherein
      the C. elegans Mi2 complex maintains genomic integrity through reinforcement of a
      chromatin landscape suitable for homology-driven repair mechanisms.

PMID- 29339411
TI  - Flagellin Glycoproteomics of the Periodontitis Associated Pathogen Selenomonas
      sputigena Reveals Previously Not Described O-glycans and Rhamnose Fragment
      Rearrangement Occurring on the Glycopeptides.
AB  - Flagellated, Gram-negative, anaerobic, crescent-shaped Selenomonas species are
      colonizers of the digestive system, where they act at the interface between
      health and disease. Selenomonas sputigena is also considered a potential human
      periodontal pathogen, but information on its virulence factors and underlying
      pathogenicity mechanisms is scarce. Here we provide the first report of a
      Selenomonas glycoprotein, showing that S. sputigena produces a diversely and
      heavily O-glycosylated flagellin C9LY14 as a major cellular protein, which
      carries various hitherto undescribed rhamnose- and N-acetylglucosamine linked O
      glycans in the range from mono- to hexasaccharides. A comprehensive glycomic and
      glycoproteomic assessment revealed extensive glycan macro- and microheterogeneity
      identified from 22 unique glycopeptide species. From the multiple sites of
      glycosylation, five were unambiguously identified on the 437-amino acid C9LY14
      protein (Thr149, Ser182, Thr199, Thr259, and Ser334), the only flagellin protein
      identified. The O-glycans additionally showed modifications by methylation and
      putative acetylation. Some O-glycans carried hitherto undescribed
      residues/modifications as determined by their respective m/z values, reflecting
      the high diversity of native S. sputigena flagellin. We also found that
      monosaccharide rearrangement occurred during collision-induced dissociation (CID)
      of protonated glycopeptide ions. This effect resulted in pseudo Y1-glycopeptide
      fragment ions that indicated the presence of additional glycosylation sites on a
      single glycopeptide. CID oxonium ions and electron transfer dissociation,
      however, confirmed that just a single site was glycosylated, showing that glycan
      to-peptide rearrangement can occur on glycopeptides and that this effect is
      influenced by the molecular nature of the glycan moiety. This effect was most
      pronounced with disaccharides. This study is the first report on O-linked
      flagellin glycosylation in a Selenomonas species, revealing that C9LY14 is one of
      the most heavily glycosylated flagellins described to date. This study
      contributes to our understanding of the largely under-investigated surface
      properties of oral bacteria. The data have been deposited to the ProteomeXchange
      with identifier PXD005859.

PMID- 29339412
TI  - The Sequence-specific Peptide-binding Activity of the Protein Sulfide Isomerase
      AGR2 Directs Its Stable Binding to the Oncogenic Receptor EpCAM.
AB  - AGR2 is an oncogenic endoplasmic reticulum (ER)-resident protein disulfide
      isomerase. AGR2 protein has a relatively unique property for a chaperone in that
      it can bind sequence-specifically to a specific peptide motif (TTIYY). A
      synthetic TTIYY-containing peptide column was used to affinity-purify AGR2 from
      crude lysates highlighting peptide selectivity in complex mixtures. Hydrogen
      deuterium exchange mass spectrometry localized the dominant region in AGR2 that
      interacts with the TTIYY peptide to within a structural loop from amino acids 131
      135 (VDPSL). A peptide binding site consensus of Tx[IL][YF][YF] was developed for
      AGR2 by measuring its activity against a mutant peptide library. Screening the
      human proteome for proteins harboring this motif revealed an enrichment in
      transmembrane proteins and we focused on validating EpCAM as a potential AGR2
      interacting protein. AGR2 and EpCAM proteins formed a dose-dependent protein
      protein interaction in vitro Proximity ligation assays demonstrated that
      endogenous AGR2 and EpCAM protein associate in cells. Introducing a single
      alanine mutation in EpCAM at Tyr251 attenuated its binding to AGR2 in vitro and
      in cells. Hydrogen-deuterium exchange mass spectrometry was used to identify a
      stable binding site for AGR2 on EpCAM, adjacent to the TLIYY motif and
      surrounding EpCAM's detergent binding site. These data define a dominant site on
      AGR2 that mediates its specific peptide-binding function. EpCAM forms a model
      client protein for AGR2 to study how an ER-resident chaperone can dock
      specifically to a peptide motif and regulate the trafficking a protein destined
      for the secretory pathway.

PMID- 29339413
TI  - Proteotranscriptomic Analysis and Discovery of the Profile and Diversity of Toxin
      like Proteins in Centipede.
AB  - Centipedes are one of the oldest venomous animals and use their venoms as weapons
      to attack prey or protect themselves. Their venoms contain various components
      with different biomedical and pharmacological properties. However, little
      attention has been paid to the profiles and diversity of their toxin-like
      proteins/peptides. In this study, we used a proteotranscriptomic approach to
      uncover the diversity of centipede toxin-like proteins in Scolopendra subspinipes
      mutilans Nine hundred twenty-three and 6,736 peptides, which were separately
      isolated from venom and torso tissues, respectively, were identified by ESI-MS/MS
      and deduced from their transcriptomes. Finally, 1369 unique proteins were
      identified in the proteome, including 100 proteins that exhibited overlapping
      expression in venom and torso tissues. Of these proteins, at least 40 proteins
      were identified as venom toxin-like proteins. Meanwhile, transcriptome mining
      identified ~10-fold more toxin-like proteins and enabled the characterization of
      the precursor architecture of mature toxin-like peptides. Importantly, combined
      with proteomic and transcriptomic analyses, 25 toxin-like proteins/peptides
      (neurotoxins accounted for 50%) were expressed outside the venom gland and
      involved in gene recruitment processes. These findings highlight the extensive
      diversity of centipede toxin-like proteins and provide a new foundation for the
      medical-pharmaceutical use of centipede toxin-like proteins. Moreover, we are the
      first group to report the gene recruitment activity of venom toxin-like proteins
      in centipede, similar to snakes.

PMID- 29339414
TI  - Assembly of Methyl Coenzyme M Reductase in the Methanogenic Archaeon
      Methanococcus maripaludis.
AB  - Methyl coenzyme M reductase (MCR) is a complex enzyme that catalyzes the final
      step in biological methanogenesis. To better understand its assembly, the
      recombinant MCR from the thermophile Methanothermococcus okinawensis (rMCRok) was
      expressed in the mesophile Methanococcus maripaludis The rMCRok was
      posttranslationally modified correctly and contained McrD and the unique nickel
      tetrapyrrole coenzyme F430 Subunits of the native M. maripaludis (MCRmar) were
      largely absent, suggesting that the recombinant enzyme was formed by an assembly
      of cotranscribed subunits. Strong support for this hypothesis was obtained by
      expressing a chimeric operon comprising the His-tagged mcrA from M. maripaludis
      and the mcrBDCG from M. okinawensis in M. maripaludis The His-tagged purified
      rMCR then contained the M. maripaludis McrA and the M. okinawensis McrBDG. The
      present study prompted us to form a working model for MCR assembly, which can be
      further tested by the heterologous expression system established here.IMPORTANCE
      Approximately 1.6% of the net primary production of plants, algae, and
      cyanobacteria are processed by biological methane production in anoxic
      environments. This accounts for about 74% of the total global methane production,
      up to 25% of which is consumed by anaerobic oxidation of methane (AOM). Methyl
      coenzyme M reductase (MCR) is the key enzyme in both methanogenesis and AOM. MCR
      is assembled as a dimer of two heterotrimers, where posttranslational
      modifications and F430 cofactors are embedded in the active sites. However, this
      complex assembly process remains unknown. Here, we established a heterologous
      expression system for MCR to learn how MCR is assembled.

PMID- 29339416
TI  - Exploring the (Almost) Unknown: Archaeal Two-Component Systems.
AB  - Two-component systems (TCS) exist in bacteria and archaea. In contrast to the
      knowledge of bacterial TCSs, little information is available on their archaeal
      counterparts. In the current issue of Journal of Bacteriology, Galperin and
      coworkers present a bioinformatics analysis of TCS genes from archaeal genome
      sequences (M. Y. Galperin, K. S. Makarova, Y. I. Wolf, and E. V. Koonin, J
      Bacteriol 200:e00681-17, 2018, https://doi.org/10.1128/JB.00681-17). This study
      identifies different aspects in which TCS-mediated signaling differs in bacteria
      and archaea and forms a sound basis for the experimental design of studies to
      increase our knowledge of this poorly investigated protein family.

PMID- 29339415
TI  - Genome-Wide Identification by Transposon Insertion Sequencing of Escherichia coli
      K1 Genes Essential for In Vitro Growth, Gastrointestinal Colonizing Capacity, and
      Survival in Serum.
AB  - Escherichia coli K1 strains are major causative agents of invasive disease of
      newborn infants. The age dependency of infection can be reproduced in neonatal
      rats. Colonization of the small intestine following oral administration of K1
      bacteria leads rapidly to invasion of the blood circulation; bacteria that avoid
      capture by the mesenteric lymphatic system and evade antibacterial mechanisms in
      the blood may disseminate to cause organ-specific infections such as meningitis.
      Some E. coli K1 surface constituents, in particular the polysialic acid capsule,
      are known to contribute to invasive potential, but a comprehensive picture of the
      factors that determine the fully virulent phenotype has not emerged so far. We
      constructed a library and constituent sublibraries of ~775,000 Tn5 transposon
      mutants of E. coli K1 strain A192PP and employed transposon-directed insertion
      site sequencing (TraDIS) to identify genes required for fitness for infection of
      2-day-old rats. Transposon insertions were lacking in 357 genes following
      recovery on selective agar; these genes were considered essential for growth in
      nutrient-replete medium. Colonization of the midsection of the small intestine
      was facilitated by 167 E. coli K1 gene products. Restricted bacterial
      translocation across epithelial barriers precluded TraDIS analysis of gut-to
      blood and blood-to-brain transits; 97 genes were required for survival in human
      serum. This study revealed that a large number of bacterial genes, many of which
      were not previously associated with systemic E. coli K1 infection, are required
      to realize full invasive potential.IMPORTANCEEscherichia coli K1 strains cause
      life-threatening infections in newborn infants. They are acquired from the mother
      at birth and colonize the small intestine, from where they invade the blood and
      central nervous system. It is difficult to obtain information from acutely ill
      patients that sheds light on physiological and bacterial factors determining
      invasive disease. Key aspects of naturally occurring age-dependent human
      infection can be reproduced in neonatal rats. Here, we employ transposon-directed
      insertion site sequencing to identify genes essential for the in vitro growth of
      E. coli K1 and genes that contribute to the colonization of susceptible rats. The
      presence of bottlenecks to invasion of the blood and cerebrospinal compartments
      precluded insertion site sequencing analysis, but we identified genes for
      survival in serum.

PMID- 29339417
TI  - Repression of VvpM Protease Expression by Quorum Sensing and the cAMP-cAMP
      Receptor Protein Complex in Vibrio vulnificus.
AB  - Septicemia-causing Vibrio vulnificus produces at least three exoproteases, VvpE,
      VvpS, and VvpM, all of which participate in interactions with human cells.
      Expression of VvpE and VvpS is induced in the stationary phase by multiple
      transcription factors, including sigma factor S, SmcR, and the cAMP-cAMP receptor
      protein (cAMP-CRP) complex. Distinct roles of VvpM, such as induction of
      apoptosis, lead us to hypothesize VvpM expression is different from that of the
      other exoproteases. Its transcription, which was found to be independent of sigma
      S, is induced at the early exponential phase and then becomes negligible upon
      entry into the stationary phase. SmcR and CRP were studied regarding the control
      of vvpM expression. Transcription of vvpM was repressed by SmcR and cAMP-CRP
      complex individually, which specifically bound to the regions -2 to +20 and +6 to
      +27, respectively, relative to the vvpM transcription initiation site.
      Derepression of vvpM gene expression was 10- to 40-fold greater in an smcR crp
      double mutant than in single-gene mutants. Therefore, these results show that the
      expression of V. vulnificus exoproteases is differentially regulated, and in this
      way, distinct proteases can engage in specific interactions with a
      host.IMPORTANCE An opportunistic human pathogen, Vibrio vulnificus produces
      multiple extracellular proteases that are involved in diverse interactions with a
      host. The total exoproteolytic activity is detected mainly in the supernatants of
      the high-cell-density cultures. However, some proteolytic activity derived from a
      metalloprotease, VvpM, was present in the supernatants of the low-cell-density
      cultures sampled at the early growth period. In this study, we present the
      regulatory mechanism for VvpM expression via repression by at least two
      transcription factors. This type of transcriptional regulation is the exact
      opposite of those for expression of the other V. vulnificus exoproteases.
      Differential regulation of each exoprotease's production then facilitates the
      pathogen's participation in the distinct interactions with a host.

PMID- 29339418
TI  - An Evolutionary/Biochemical Connection Between Promoter- and Primer-Dependent
      Polymerases Revealed by Selective Evolution of Ligands by Exponential Enrichment
      (SELEX).
AB  - DNA polymerases (DNAPs) recognize 3' recessed termini on duplex DNA and carry out
      nucleotide catalysis. Unlike promoter-specific RNA polymerases (RNAPs), no
      sequence specificity is required for binding or initiation of catalysis. Despite
      this, previous results indicate that viral reverse transcriptases bind much more
      tightly to DNA primers that mimic the polypurine tract. In the current report,
      primer sequences that bind with high affinity to Taq and Klenow polymerases were
      identified using a modified Selective Evolution of Ligands by Exponential
      Enrichment (SELEX) approach. Two Taq-specific primers that bound ~10 (Taq1) and
      over 100 (Taq2) times more stably than controls to Taq were identified. Taq1
      contained 8 nucleotides (5' -CACTAAAG-3') that matched the phage T3 RNAP "core"
      promoter. Both primers dramatically outcompeted primers with similar binding
      thermodynamics in PCR reactions. Similarly, exonuclease minus Klenow polymerase
      also selected a high affinity primer that contained a related core promoter
      sequence from phage T7 RNAP (5' -ACTATAG-3'). For both Taq and Klenow, even small
      modifications to the sequence resulted in large losses in binding affinity
      suggesting that binding was highly sequence-specific. The results are discussed
      in the context of possible effects on multi-primer (multiplex) PCR assays,
      molecular information theory, and the evolution of RNAPs and DNAPs.Importance
      This work further demonstrates that primer-dependent DNA polymerases can have
      strong sequence biases leading to dramatically tighter binding to specific
      sequences. These may be related to biological function, or be a consequences of
      the structural architecture of the enzyme. New sequence specificity for Taq and
      Klenow polymerases were uncovered and among them were sequences that contained
      the core promoter elements from T3 and T7 phage RNA polymerase promoters. This
      suggests the intriguing possibility that phage RNA polymerases exploited
      intrinsic binding affinities of ancestral DNA polymerases to develop their
      promotors. Conversely, DNA polymerases could have evolved from related RNA
      polymerases and retained the intrinsic binding preference despite there being no
      clear function for such a preference in DNA biology.

PMID- 29339419
TI  - LINC00152 down-regulated miR-193a-3p to enhance MCL1 expression and promote
      gastric cancer cells proliferation.
AB  - The present work aimed to probe into the effect of long non-coding RNA (lncRNA)
      LINC00152 on gastric cancer (GC) cells proliferation by regulating miR-193a-3p
      and its target gene MCL1 Transfected si-LINC00152 was used to down-regulate
      LINC00152, and cells proliferation was measured by the cell counting kit-8 (CCK
      8) assay. Cell apoptosis and cell cycle were analyzed by flow cytometry (FCM).
      Besides, we also detected the potential functional effects of differential
      expression of LINC00152 in vivo using nude mouse xenograft model. We
      overexpressed and downexpressed miR-193a-3p to study the in vitro effect of miR
      193a-3p on GC cells proliferation and vitality. And MCL1 was silenced by shRNA to
      investigate the effect of MCL1 on proliferation of GC cells. In this research,
      LINC00152 was proven to have a higher expression level in GC tissues than in the
      adjacent normal tissues. GC cells proliferation was inhibited after LINC00152 was
      down-regulated. LINC00152 inhibited the expression of miR-193a-3p, which
      negatively regulated MCL1 In addition, GC cells proliferation was inhibited by
      cell transfection with shRNA-MCL1, and enhanced by transfection with miR-193a-3p
      mimics. Our study suggested that LINC00152 was overexpressed in GC tissues, and
      it down-regulated miR-193a-3p to enhance MCL1 expression thereby promoting GC
      cells proliferation.

PMID- 29339420
TI  - LINC00673 rs11655237 C>T confers neuroblastoma susceptibility in Chinese
      population.
AB  - Neuroblastoma, which accounts for approximately 10% of all pediatric cancer
      related deaths, has become a therapeutic challenge and global burden attributed
      to poor outcomes and mortality rates of its high-risk form. Previous genome-wide
      association studies (GWASs) identified the LINC00673 rs11655237 C>T polymorphism
      to be associated with the susceptibility of several malignant tumors. However,
      the association between this polymorphism and neuroblastoma susceptibility is not
      clear. We genotyped LINC00673 rs11655237 C>T in 393 neuroblastoma patients in
      comparison with 812 age-, gender-, and ethnicity-matched healthy controls. We
      found a significant association between the LINC00673 rs11655237 C>T polymorphism
      and neuroblastoma risk (TT compared with CC: adjusted odds ratio (OR) =1.80, 95%
      confidence interval (CI) =1.06-3.06, P=0.029; TT/CT compared with CC: adjusted OR
      =1.31, 95% CI =1.02-1.67, P=0.033; and T compared with C: adjusted OR =1.29, 95%
      CI =1.06-1.58, P=0.013). Furthermore, stratified analysis indicated that the
      rs11655237 T allele carriers were associated with increased neuroblastoma risk
      for patients with tumor originating from the adrenal gland (adjusted OR =1.51,
      95% CI =1.06-2.14, P=0.021) and International Neuroblastoma Staging System (INSS)
      stage IV disease (adjusted OR =1.60, 95% CI =1.12-2.30, P=0.011). In conclusion,
      we verified that the LINC00673 rs11655237 C>T polymorphism might be associated
      with neuroblastoma susceptibility. Prospective studies with a large sample size
      and different ethnicities are needed to validate our findings.

PMID- 29339421
TI  - HIF1A gene rs10873142 polymorphism is associated with risk of chronic obstructive
      pulmonary disease in a Chinese Han population: a case-control study.
AB  - Chronic obstructive pulmonary disease (COPD) is a type of obstructive lung
      disease characterized by long-term poor airflow. Recently, variants in the
      hypoxia inducible factor 1alpha (HIF1A) gene were found to be associated with
      COPD risk. The present study aimed to identify whether rs10873142 polymorphism
      (an intronic polymorphism) in HIF1A gene was related to COPD in a Chinese
      population. We genotyped HIF1A gene rs10873142 polymorphism in a case-control
      study with 235 COPD cases and 548 controls in a Chinese Han population. Odd
      ratios (ORs) and 95% confidence intervals (CIs) were estimated using the chi
      squared (chi2) test, genetic model analysis, and stratification analysis. In the
      genetic model analysis, we found that the TT genotype (TT compared with CC: OR:
      1.63; 95% CI: 1.02-2.60; P=0.042) and T allele (T compared with C: OR: 1.29;
      95%CI, 1.02-1.60; P=0.032) showed significant correlation with the risk of COPD.
      However, in stratification analyses of age, BMI, and forced expiratory volume in
      1 s (FEV1)/FEV, we failed to find any association between HIF1A gene rs10873142
      polymorphism with COPD risk. The present study supports that HIF1A gene
      rs10873142 polymorphism may be associated with increased risk of COPD in a
      Chinese Han population. To the best of our knowledge, this is the first case
      control study uncovering that the HIF1A gene rs10873142 polymorphism increases
      the risk of COPD in a Chinese Han population.

PMID- 29339422
TI  - The Role of Angiopoietin-like Protein 4 in Phenylephrine-induced Cardiomyocyte
      Hypertrophy.
AB  - Angiopoietin-like protein 4 (ANGPTL4) is a multifunctional secreted protein that
      can be induced by fasting, hypoxia and glucocorticoids. ANGPTL4 has been
      associated with a variety of diseases, however, the role of ANGPTL4 in cardiac
      hypertrophy remains poorly understood. In our study, we aimed to explore the
      effect of ANGPTL4 on phenylephrine (PE)-induced cardiomyocyte hypertrophy. Our
      results showed that knockdown of ANGPTL4 expression significantly exacerbated
      cardiomyocyte hypertrophy, as demonstrated by increased hypertrophic marker
      expression, including ANP and cell surface area. Moreover, significantly reduced
      fatty acid oxidation, as featured by decreased CPT-1 levels, was observed in
      hypertrophic cardiomyocytes following ANGPTL4 downregulation. Furthermore,
      knockdown of ANGPLT4 led to downregulated expression of PPARalpha, which is the
      key regulator of cardiac fatty acid oxidation. In addition, ANGPTL4 silencing
      promoted the activation of JNK1/2, and JNK1/2 signaling blockade could restore
      the level of PPARalpha and significantly ameliorate the ANGPTL4 knockdown-induced
      cardiomyocyte hypertrophy. Therefore, our study demonstrated that ANGPTL4
      regulates PPARalpha through JNK1/2 signaling and is required for the inhibition
      of cardiomyocyte hypertrophy.

PMID- 29339423
TI  - Immune Protection against Lethal Fungal-Bacterial Intra-Abdominal Infections.
AB  - Polymicrobial intra-abdominal infections (IAIs) are clinically prevalent and
      cause significant morbidity and mortality, especially those involving fungi. Our
      laboratory developed a mouse model of IAI and demonstrated that intraperitoneal
      inoculation with Candida albicans or other virulent non-albicans Candida (NAC)
      species plus Staphylococcus aureus resulted in 70 to 80% mortality in 48 to 72 h
      due to robust local and systemic inflammation (sepsis). Surprisingly, inoculation
      with Candida dubliniensis or Candida glabrata with S. aureus resulted in minimal
      mortality, and rechallenge of these mice with lethal C. albicans/S. aureus (i.e.,
      coninfection) resulted in >90% protection. The purpose of this study was to
      define requirements for C. dubliniensis/S. aureus-mediated protection and
      interrogate the mechanism of the protective response. Protection was conferred by
      C. dubliniensis alone or by killed C. dubliniensis plus live S. aureusS. aureus
      alone was not protective, and killed S. aureus compromised C. dubliniensis
      induced protection. C. dubliniensis/S. aureus also protected against lethal
      challenge by NAC plus S. aureus and could protect for a long-term duration (60
      days between primary challenge and C. albicans/S. aureus rechallenge).
      Unexpectedly, mice deficient in T and B cells (Rag-1 knockouts [KO]) survived
      both the initial C. dubliniensis/S. aureus challenge and the C. albicans/S.
      aureus rechallenge, indicating that adaptive immunity did not play a role.
      Similarly, mice depleted of macrophages prior to rechallenge were also protected.
      In contrast, protection was associated with high numbers of Gr-1hi
      polymorphonuclear leukocytes (PMNLs) in peritoneal lavage fluid within 4 h of
      rechallenge, and in vivo depletion of Gr-1+ cells prior to rechallenge abrogated
      protection. These results suggest that Candida species can induce protection
      against a lethal C. albicans/S. aureus IAI that is mediated by PMNLs and
      postulated to be a unique form of trained innate immunity.IMPORTANCE
      Polymicrobial intra-abdominal infections are clinically devastating infections
      with high mortality rates, particularly those involving fungal pathogens,
      including Candida species. Even in patients receiving aggressive antimicrobial
      therapy, mortality rates remain unacceptably high. There are no available
      vaccines against IAI, which is complicated by the polymicrobial nature of the
      infection. IAI leads to lethal systemic inflammation (sepsis), which is difficult
      to target pharmacologically, as components of the inflammatory response are also
      needed to control the infection. Our studies demonstrate that prior inoculation
      with low-virulence Candida species provides strong protection against subsequent
      lethal infection with C. albicans and S. aureus Surprisingly, protection is long
      lived but not mediated by adaptive (specific) immunity. Instead, protection is
      dependent on cells of the innate immune system (nonspecific immunity) and
      provides protection against other virulent Candida species. This discovery
      implies that a form of trained innate immunity may be clinically effective
      against polymicrobial IAI.

PMID- 29339424
TI  - Clostridium sordellii Pathogenicity Locus Plasmid pCS1-1 Encodes a Novel
      Clostridial Conjugation Locus.
AB  - A major virulence factor in Clostridium sordellii-mediated infection is the toxin
      TcsL, which is encoded within a region of the genome called the pathogenicity
      locus (PaLoc). C. sordellii isolates carry the PaLoc on the pCS1 family of
      plasmids, of which there are four characterized members. Here, we determined the
      potential mobility of pCS1 plasmids and characterized a fifth unique pCS1 member.
      Using a derivative of the pCS1-1 plasmid from strain ATCC 9714 which had been
      marked with the ermB erythromycin resistance gene, conjugative transfer into a
      recipient C. sordellii isolate, R28058, was demonstrated. Bioinformatic analysis
      of pCS1-1 identified a novel conjugation gene cluster defined as the C. sordellii
      transfer (cst) locus. Interruption of genes within the cst locus resulted in loss
      of pCS1-1 transfer, which was restored upon complementation in trans These
      studies provided clear evidence that genes within the cst locus are essential for
      the conjugative transfer of pCS1-1. The cst locus is present on all pCS1
      subtypes, and homologous loci were identified on toxin-encoding plasmids from
      Clostridium perfringens and Clostridium botulinum and also carried within genomes
      of Clostridium difficile isolates, indicating that it is a widespread clostridial
      conjugation locus. The results of this study have broad implications for the
      dissemination of toxin genes and, potentially, antibiotic resistance genes among
      members of a diverse range of clostridial pathogens, providing these
      microorganisms with a survival advantage within the infected host.IMPORTANCEC.
      sordellii is a bacterial pathogen that causes severe infections in humans and
      animals, with high mortality rates. While the pathogenesis of C. sordellii
      infections is not well understood, it is known that the toxin TcsL is an
      important virulence factor. Here, we have shown the ability of a plasmid carrying
      the tcsL gene to undergo conjugative transfer between distantly related strains
      of C. sordellii, which has far-reaching implications for the ability of C.
      sordellii to acquire the capacity to cause disease. Plasmids that carry tcsL
      encode a previously uncharacterized conjugation locus, and individual genes
      within this locus were shown to be required for conjugative transfer.
      Furthermore, homologues on toxin plasmids from other clostridial species were
      identified, indicating that this region represents a novel clostridial
      conjugation locus. The results of this study have broad implications for the
      dissemination of virulence genes among members of a diverse range of clostridial
      pathogens.

PMID- 29339426
TI  - Gut Microbial Glycerol Metabolism as an Endogenous Acrolein Source.
AB  - Acrolein is a highly reactive electrophile causing toxic effects, such as DNA and
      protein adduction, oxidative stress, endoplasmic reticulum stress, immune
      dysfunction, and membrane damage. This Opinion/Hypothesis provides an overview of
      endogenous and exogenous acrolein sources, acrolein's mode of action, and its
      metabolic fate. Recent reports underpin the finding that gut microbial glycerol
      metabolism leading to the formation of reuterin is an additional source of
      endogenous acrolein. Reuterin is an antimicrobial multicomponent system
      consisting of 3-hydroxypropionaldehyde, its dimer and hydrate, and also acrolein.
      The major conclusion is that gut microbes can metabolize glycerol to reuterin and
      that this transformation occurs in vivo Given the known toxicity of acrolein, the
      observation that acrolein is formed in the gut necessitates further
      investigations on functional relevance for gut microbiota and the host.

PMID- 29339425
TI  - Secondary Metabolism and Interspecific Competition Affect Accumulation of
      Spontaneous Mutants in the GacS-GacA Regulatory System in Pseudomonas protegens.
AB  - Secondary metabolites are synthesized by many microorganisms and provide a
      fitness benefit in the presence of competitors and predators. Secondary
      metabolism also can be costly, as it shunts energy and intermediates from primary
      metabolism. In Pseudomonas spp., secondary metabolism is controlled by the GacS
      GacA global regulatory system. Intriguingly, spontaneous mutations in gacS or
      gacA (Gac- mutants) are commonly observed in laboratory cultures. Here we
      investigated the role of secondary metabolism in the accumulation of Gac- mutants
      in Pseudomonas protegens strain Pf-5. Our results showed that secondary
      metabolism, specifically biosynthesis of the antimicrobial compound pyoluteorin,
      contributes significantly to the accumulation of Gac- mutants. Pyoluteorin
      biosynthesis, which poses a metabolic burden on the producer cells, but not
      pyoluteorin itself, leads to the accumulation of the spontaneous mutants.
      Interspecific competition also influenced the accumulation of the Gac- mutants: a
      reduced proportion of Gac- mutants accumulated when P. protegens Pf-5 was
      cocultured with Bacillus subtilis than in pure cultures of strain Pf-5. Overall,
      our study associated a fitness trade-off with secondary metabolism, with
      metabolic costs versus competitive benefits of production influencing the
      evolution of P. protegens, assessed by the accumulation of Gac-
      mutants.IMPORTANCE Many microorganisms produce antibiotics, which contribute to
      ecologic fitness in natural environments where microbes constantly compete for
      resources with other organisms. However, biosynthesis of antibiotics is costly
      due to the metabolic burdens of the antibiotic-producing microorganism. Our
      results provide an example of the fitness trade-off associated with antibiotic
      production. Under noncompetitive conditions, antibiotic biosynthesis led to
      accumulation of spontaneous mutants lacking a master regulator of antibiotic
      production. However, relatively few of these spontaneous mutants accumulated when
      a competitor was present. Results from this work provide information on the
      evolution of antibiotic biosynthesis and provide a framework for their discovery
      and regulation.

PMID- 29339427
TI  - Pandemic Paradox: Early Life H2N2 Pandemic Influenza Infection Enhanced
      Susceptibility to Death during the 2009 H1N1 Pandemic.
AB  - Recent outbreaks of H5, H7, and H9 influenza A viruses in humans have served as a
      vivid reminder of the potentially devastating effects that a novel pandemic could
      exert on the modern world. Those who have survived infections with influenza
      viruses in the past have been protected from subsequent antigenically similar
      pandemics through adaptive immunity. For example, during the 2009 H1N1 "swine
      flu" pandemic, those exposed to H1N1 viruses that circulated between 1918 and the
      1940s were at a decreased risk for mortality as a result of their previous
      immunity. It is also generally thought that past exposures to antigenically
      dissimilar strains of influenza virus may also be beneficial due to cross
      reactive cellular immunity. However, cohorts born during prior heterosubtypic
      pandemics have previously experienced elevated risk of death relative to
      surrounding cohorts of the same population. Indeed, individuals born during the
      1890 H3Nx pandemic experienced the highest levels of excess mortality during the
      1918 "Spanish flu." Applying Serfling models to monthly mortality and influenza
      circulation data between October 1997 and July 2014 in the United States and
      Mexico, we show corresponding peaks in excess mortality during the 2009 H1N1
      "swine flu" pandemic and during the resurgent 2013-2014 H1N1 outbreak for those
      born at the time of the 1957 H2N2 "Asian flu" pandemic. We suggest that the
      phenomenon observed in 1918 is not unique and points to exposure to pandemic
      influenza early in life as a risk factor for mortality during subsequent
      heterosubtypic pandemics.IMPORTANCE The relatively low mortality experienced by
      older individuals during the 2009 H1N1 influenza virus pandemic has been well
      documented. However, reported situations in which previous influenza virus
      exposures have enhanced susceptibility are rare and poorly understood. One such
      instance occurred in 1918-when those born during the heterosubtypic 1890 H3Nx
      influenza virus pandemic experienced the highest levels of excess mortality.
      Here, we demonstrate that this phenomenon was not unique to the 1918 H1N1
      pandemic but that it also occurred during the contemporary 2009 H1N1 pandemic and
      2013-2014 H1N1-dominated season for those born during the heterosubtypic 1957
      H2N2 "Asian flu" pandemic. These data highlight the heretofore underappreciated
      phenomenon that, in certain instances, prior exposure to pandemic influenza virus
      strains can enhance susceptibility during subsequent pandemics. These results
      have important implications for pandemic risk assessment and should inform
      laboratory studies aimed at uncovering the mechanism responsible for this effect.

PMID- 29339428
TI  - Mucosal Infections and Invasive Potential of Nonencapsulated Streptococcus
      pneumoniae Are Enhanced by Oligopeptide Binding Proteins AliC and AliD.
AB  - Nonencapsulated Streptococcus pneumoniae (NESp) is an emerging human pathogen
      that colonizes the nasopharynx and is associated with noninvasive diseases such
      as otitis media (OM), conjunctivitis, and nonbacteremic pneumonia. Since capsule
      expression was previously thought to be necessary for establishment of invasive
      pneumococcal disease (IPD), serotype-specific polysaccharide capsules are
      targeted by currently licensed pneumococcal vaccines. Yet, NESp expressing
      oligopeptide binding proteins AliC and AliD have been isolated during IPD. Thus,
      we hypothesize AliC and AliD are major NESp virulence determinants that
      facilitate persistence and development of IPD. Our study reveals that NESp
      expressing AliC and AliD have intensified virulence compared to isogenic mutants.
      Specifically, we demonstrate AliC and AliD enhance murine nasopharyngeal
      colonization and pulmonary infection and are required for OM in a chinchilla
      model. Furthermore, AliC and AliD increase pneumococcal survival in chinchilla
      whole blood and aid in resistance to killing by human leukocytes. Comparative
      proteome analysis revealed significant alterations in protein levels when AliC
      and AliD were absent. Virulence-associated proteins, including a pneumococcal
      surface protein C variant (CbpAC), were significantly downregulated, while
      starvation response indicators were upregulated in the double mutant relative to
      wild-type levels. We also reveal that differentially expressed CbpAC was
      essential for NESp adherence to epithelial cells, virulence during OM, reduction
      of C3b deposition on the NESp surface, and binding to nonspecific IgA.
      Altogether, the rise in NESp prevalence urges the need to understand how NESp
      establishes disease and persists in a host. This study highlights the roles of
      AliC, AliD, and CbpAC in the pathogenesis of NESp.IMPORTANCE Despite the
      effective, widespread use of licensed pneumococcal vaccines over many decades,
      pneumococcal infections remain a worldwide burden resulting in high morbidity and
      mortality. NESp subpopulations are rapidly rising in the wake of capsule-targeted
      vaccine strategies, yet there is very little knowledge on NESp pathogenic
      potential and virulence mechanisms. Although NESp lacks a protective capsule,
      NESp lineages expressing AliC and AliD have been associated with systemic
      infections. Furthermore, higher antibiotic resistance rates and transformation
      efficiencies associated with emerging NESp threaten treatment strategies needed
      to control pneumococcal infections and transmission. Elucidating how NESp
      survives within a host and establishes disease is necessary for development of
      broadened pneumococcal prevention methods. Our study identifies virulence
      determinants and host survival mechanisms employed by NESp with a high pathogenic
      potential. Moreover, our study also identifies virulence determinants shared by
      NESp and encapsulated strains that may serve as broad prevention and therapeutic
      targets.

PMID- 29339430
TI  - Simultaneous Binding of Multiple EF-Tu Copies to Translating Ribosomes in Live
      Escherichia coli.
AB  - In bacteria, elongation factor Tu is a translational cofactor that forms ternary
      complexes with aminoacyl-tRNA (aa-tRNA) and GTP. Binding of a ternary complex to
      one of four flexible L7/L12 units on the ribosome tethers a charged tRNA in close
      proximity to the ribosomal A site. Two sequential tests for a match between the
      aa-tRNA anticodon and the current mRNA codon then follow. Because one elongation
      cycle can occur in as little as 50 ms and the vast majority of aa-tRNA copies are
      not cognate with the current mRNA codon, this testing must occur rapidly. We
      present a single-molecule localization and tracking study of fluorescently
      labeled EF-Tu in live Escherichia coli Imaging at 2 ms/frame distinguishes 60%
      slowly diffusing EF-Tu copies (assigned as transiently bound to translating
      ribosome) from 40% rapidly diffusing copies (assigned as a mixture of free
      ternary complexes and free EF-Tu). Combining these percentages with copy number
      estimates, we infer that the four L7/L12 sites are essentially saturated with
      ternary complexes in vivo. The results corroborate an earlier inference that all
      four sites can simultaneously tether ternary complexes near the A site, creating
      a high local concentration that may greatly enhance the rate of testing of aa
      tRNAs. Our data and a combinatorial argument both suggest that the initial
      recognition test for a codon-anticodon match occurs in less than 1 to 2 ms per aa
      tRNA copy. The results refute a recent study (A. Plochowietz, I. Farrell, Z.
      Smilansky, B. S. Cooperman, and A. N. Kapanidis, Nucleic Acids Res 45:926-937,
      2016, https://doi.org/10.1093/nar/gkw787) of tRNA diffusion in E. coli that
      inferred that aa-tRNAs arrive at the ribosomal A site as bare monomers, not as
      ternary complexes.IMPORTANCE Ribosomes catalyze translation of the mRNA codon
      sequence into the corresponding sequence of amino acids within the nascent
      polypeptide chain. Polypeptide elongation can be as fast as 50 ms per added amino
      acid. Each amino acid arrives at the ribosome as a ternary complex comprising an
      aminoacyl-tRNA (aa-tRNA), an elongation factor called EF-Tu, and GTP. There are
      43 different aa-tRNAs in use, only one of which typically matches the current
      mRNA codon. Thus, ternary complexes must be tested very rapidly. Here we use
      fluorescence-based single-molecule methods that locate and track single EF-Tu
      copies in E. coli Fast and slow diffusive behavior determines the fraction of EF
      Tu copies that are ribosome bound. We infer simultaneous tethering of ~4 ternary
      complexes to the ribosome, which may facilitate rapid initial testing for codon
      matching on a time scale of less than 1 to 2 ms per aa-tRNA.

PMID- 29339429
TI  - The Biochemistry of Sensing: Enteric Pathogens Regulate Type III Secretion in
      Response to Environmental and Host Cues.
AB  - Enteric pathogens employ sophisticated strategies to colonize and infect
      mammalian hosts. Gram-negative bacteria, such as Escherichia coli, Salmonella,
      and Campylobacter jejuni, are among the leading causes of gastrointestinal tract
      infections worldwide. The virulence strategies of many of these Gram-negative
      pathogens rely on type III secretion systems (T3SSs), which are macromolecular
      syringes that translocate bacterial effector proteins directly into the host
      cytosol. However, synthesis of T3SS proteins comes at a cost to the bacterium in
      terms of growth rate and fitness, both in the environment and within the host.
      Therefore, expression of the T3SS must be tightly regulated to occur at the
      appropriate time and place during infection. Enteric pathogens have thus evolved
      regulatory mechanisms to control expression of their T3SSs in response to
      specific environmental and host cues. These regulatory cascades integrate
      multiple physical and chemical signals through complex transcriptional networks.
      Although the power of bacterial genetics has allowed elucidation of many of these
      networks, the biochemical interactions between signal and sensor that initiate
      the signaling cascade are often poorly understood. Here, we review the physical
      and chemical signals that Gram-negative enteric pathogens use to regulate T3SS
      expression during infection. We highlight the recent structural and functional
      studies that have elucidated the biochemical properties governing both the
      interaction between sensor and signal and the mechanisms of signal transduction
      from sensor to downstream transcriptional networks.

PMID- 29339431
TI  - Molecular Insights into Function and Competitive Inhibition of Pseudomonas
      aeruginosa Multiple Virulence Factor Regulator.
AB  - New approaches to antimicrobial drug discovery are urgently needed to combat
      intractable infections caused by multidrug-resistant (MDR) bacteria. Multiple
      virulence factor regulator (MvfR or PqsR), a Pseudomonas aeruginosa quorum
      sensing transcription factor, regulates functions important in both acute and
      persistent infections. Recently identified non-ligand-based benzamine
      benzimidazole (BB) inhibitors of MvfR suppress both acute and persistent P.
      aeruginosa infections in mice without perturbing bacterial growth. Here, we
      elucidate the crystal structure of the MvfR ligand binding domain (LBD) in
      complex with one potent BB inhibitor, M64. Structural analysis indicated that M64
      binds, like native ligands, to the MvfR hydrophobic cavity. A hydrogen bond and
      pi interaction were found to be important for MvfR-M64 affinity. Surface plasmon
      resonance analysis demonstrated that M64 is a competitive inhibitor of MvfR.
      Moreover, a protein engineering approach revealed that Gln194 and Tyr258 are
      critical for the interaction between MvfR and M64. Random mutagenesis of the full
      length MvfR protein identified a single-amino-acid substitution, I68F, at a DNA
      binding linker domain that confers M64 insensitivity. In the presence of M64,
      I68F but not the wild-type (WT) MvfR protein retained DNA binding ability. Our
      findings strongly suggest that M64 promotes conformational change at the DNA
      binding domain of MvfR and that the I68F mutation may compensate for this change,
      indicating allosteric inhibition. This work provides critical new insights into
      the molecular mechanism of MvfR function and inhibition that could aid in the
      optimization of anti-MvfR compounds and improve our understanding of MvfR
      regulation.IMPORTANCEPseudomonas aeruginosa is an opportunistic Gram-negative
      pathogen that causes serious acute, persistent, and relapsing infections. New
      approaches to antimicrobial drug discovery are urgently needed to combat
      intractable infections caused by this pathogen. The Pseudomonas aeruginosa quorum
      sensing transcription factor MvfR regulates functions important in both acute and
      persistent infections. We used recently identified inhibitors of MvfR to perform
      structural studies and reveal important insights that would benefit the
      optimization of anti-MvfR compounds. Altogether, the results reported here
      provide critical detailed mechanistic insights into the function of MvfR domains
      that may benefit the optimization of the chemical, pharmacological, and safety
      properties of MvfR antagonist series.

PMID- 29339432
TI  - Deregulation of HDAC5 by Viral Interferon Regulatory Factor 3 Plays an Essential
      Role in Kaposi's Sarcoma-Associated Herpesvirus-Induced Lymphangiogenesis.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent for
      Kaposi's sarcoma (KS), which is one of the most common HIV-associated neoplasms.
      The endothelium is the thin layer of squamous cells where vascular blood
      endothelial cells (BECs) line the interior surface of blood vessels and lymphatic
      endothelial cells (LECs) are in direct contact with lymphatic vessels. The KS
      lesions contain a prominent compartment of neoplastic spindle morphology cells
      that are closely related to LECs. Furthermore, while KSHV can infect both LECs
      and BECs in vitro, its infection activates genetic programming related to
      lymphatic endothelial cell fate, suggesting that lymphangiogenic pathways are
      involved in KSHV infection and malignancy. Here, we report for the first time
      that viral interferon regulatory factor 3 (vIRF3) is readily detected in over 40%
      of KS lesions and that vIRF3 functions as a proangiogenic factor, inducing
      hypersprouting formation and abnormal growth in a LEC-specific manner. Mass
      spectrometry analysis revealed that vIRF3 interacted with histone deacetylase 5
      (HDAC5), which is a signal-responsive regulator for vascular homeostasis. This
      interaction blocked the phosphorylation-dependent cytosolic translocation of
      HDAC5 and ultimately altered global gene expression in LECs but not in BECs.
      Consequently, vIRF3 robustly induced spindle morphology and hypersprouting
      formation of LECs but not BECs. Finally, KSHV infection led to the hypersprouting
      formation of LECs, whereas infection with a DeltavIRF3 mutant did not do so.
      Collectively, our data indicate that vIRF3 alters global gene expression and
      induces a hypersprouting formation in an HDAC5-binding-dependent and LEC-specific
      manner, ultimately contributing to KSHV-associated pathogenesis.IMPORTANCE
      Several lines of evidences indicate that KSHV infection of LECs induces
      pathological lymphangiogenesis and that the results resemble KS-like spindle
      morphology. However, the underlying molecular mechanism remains unclear. Here, we
      demonstrated that KSHV vIRF3 is readily detected in over 40% of various KS
      lesions and functions as a potent prolymphangiogenic factor by blocking the
      phosphorylation-dependent cytosolic translocation of HDAC5, which in turn
      modulates global gene expression in LECs. Consequently, vIRF3-HDAC5 interaction
      contributes to virus-induced lymphangiogenesis. The results of this study suggest
      that KSHV vIRF3 plays a crucial role in KSHV-induced malignancy.

PMID- 29339433
TI  - Five-Year Mortality After Transient Ischemic Attack: Focus on Cardiometabolic
      Comorbidity and Hospital Readmission.
AB  - BACKGROUND AND PURPOSE: We aimed at providing estimates of mortality associated
      with cardiometabolic comorbidity and incident readmission from cardiometabolic as
      compared with noncardiometabolic conditions after a first transient ischemic
      attack. METHODS: Between 2000 and 2015, patients hospitalized for a first
      transient ischemic attack were examined for cardiometabolic comorbidities
      (diabetes mellitus, coronary artery disease, heart failure, and atrial
      fibrillation), 5-year incident hospitalization, and time to death. RESULTS: Of
      251 patients with transient ischemic attack, 134 (53%) had at least 1 and 55
      (22%) had at least 2 cardiometabolic conditions. By 5 years, 491 readmissions
      (134 [27%] cardiometabolic and 357 [73%] noncardiometabolic) and 75 deaths (27
      [36%] cardiometabolic and 47 [64%] noncardiometabolic) were observed. Mortality
      was increased with any concurrent cardiometabolic comorbidity (hazard ratio,
      1.89; 95% confidence interval, 1.17-3.03; P=0.0089) with multiplicative mortality
      risk from a combination of coronary artery disease and heart failure. Each
      hospitalization was associated with a 1.5-fold risk of death (95% confidence
      interval, 1.37-1.64; P<0.0001). Risk of cardiometabolic and noncardiometabolic
      mortality was correlated with the corresponding category-specific readmission.
      CONCLUSIONS: Among patients hospitalized for first transient ischemic attack, 5
      year mortality is associated with concurrent cardiometabolic comorbidity and
      rates of subsequent hospitalization.

PMID- 29339434
TI  - Cerebrovascular Outcomes With Proton Pump Inhibitors and Thienopyridines: A
      Systematic Review and Meta-Analysis.
AB  - BACKGROUND AND PURPOSE: Pharmacokinetic and prior studies on thienopyridine and
      proton pump inhibitors (PPI) coadministration provide conflicting data for
      cardiovascular outcomes, whereas there is no established evidence on the
      association of concomitant use of PPI and thienopyridines with adverse
      cerebrovascular outcomes. METHODS: We conducted a systematic review and meta
      analysis of randomized controlled trials and cohort studies from inception to
      July 2017, reporting following outcomes among patients treated with
      thienopyridine and PPI versus thienopyridine alone (1) ischemic stroke, (2)
      combined ischemic or hemorrhagic stroke, (3) composite outcome of stroke,
      myocardial infarction (MI), and cardiovascular death, (4) MI, (5) all-cause
      mortality, and (6) major or minor bleeding events. After the unadjusted analyses
      of risk ratios, we performed additional analyses of studies reporting hazard
      ratios adjusted for potential confounders. RESULTS: We identified 22 studies (12
      randomized controlled trials and 10 cohort studies) comprising 131 714 patients.
      Concomitant use of PPI with thienopyridines was associated with increased risk of
      ischemic stroke (risk ratio, 1.74; 95% confidence interval [CI], 1.41-2.16;
      P<0.001), composite stroke/MI/cardiovascular death (risk ratio, 1.14; 95% CI,
      1.01-1.29; P=0.04), and MI (risk ratio, 1.19; 95% CI, 1.00-1.40; P=0.05).
      Likewise, in adjusted analyses concomitant use of PPI with thienopyridines was
      again associated with increased risk of stroke (hazard ratios adjusted, 1.30; 95%
      CI, 1.04-1.61; P=0.02), composite stroke/MI/cardiovascular death (hazard ratios
      adjusted, 1.23; 95% CI, 1.03-1.47; P=0.02), but not with MI (hazard ratios
      adjusted, 1.19; 95% CI, 0.93-1.52; P=0.16). CONCLUSIONS: Co-prescription of PPI
      and thienopyridines increases the risk of incident ischemic strokes and composite
      stroke/MI/cardiovascular death. Our findings corroborate the current guidelines
      for PPI deprescription and pharmacovigilance, especially in patients treated with
      thienopyridines.

PMID- 29339436
TI  - Rewired Notch/p53 by Numb'ing Mdm2.
AB  - Although numerous pathways are known to control the tumor suppressor protein p53,
      coordinated regulation of the p53-Notch axis by Numb may have an even more
      remarkable impact. In this issue, Colaluca at al. (2018. J. Cell Biol.
      https://doi.org/10.1083/jcb.201709092) reveal an unexpected role of a newly
      characterized Numb splice variant in the regulation of p53, which may have
      significant implications for therapeutic intervention in breast cancer.

PMID- 29339435
TI  - Corrected and Republished from: The COP9 Signalosome Interacts with and Regulates
      Interferon Regulatory Factor 5 Protein Stability.
AB  - The transcription factor interferon regulatory factor 5 (IRF5) exerts crucial
      functions in the regulation of host immunity against extracellular pathogens, DNA
      damage-induced apoptosis, death receptor signaling, and macrophage polarization.
      Tight regulation of IRF5 is thus warranted for an efficient response to
      extracellular stressors and for limiting autoimmune and inflammatory responses.
      Here we report that the COP9 signalosome (CSN), a general modulator of diverse
      cellular and developmental processes, associates constitutively with IRF5 and
      promotes its protein stability. The constitutive CSN/IRF5 interaction was
      identified using proteomics and confirmed by endogenous immunoprecipitations. The
      CSN/IRF5 interaction occurred on the carboxyl and amino termini of IRF5; a single
      internal deletion (Delta455-466) was found to significantly reduce IRF5 protein
      stability. CSN3 was identified as a direct interacting partner of IRF5, and
      knockdown of this subunit with small interfering RNAs (siRNAs) resulted in
      enhanced degradation. Degradation was further augmented by knockdown of CSN1 and
      CSN3 together. The ubiquitin E1 inhibitor UBEI-41 or the proteasome inhibitor
      MG132 prevented IRF5 degradation, supporting that its stability is regulated by
      the ubiquitin-proteasome system. Importantly, activation of IRF5 by the death
      receptor ligand tumor necrosis factor (TNF)-related apoptosis-inducing ligand
      (TRAIL) resulted in enhanced degradation via loss of the CSN/IRF5 interaction.
      This study defines the CSN as a new interacting partner of IRF5 that controls its
      stability.

PMID- 29339437
TI  - SPR2 protects minus ends to promote severing and reorientation of plant cortical
      microtubule arrays.
AB  - The cortical microtubule arrays of higher plants are organized without
      centrosomes and feature treadmilling polymers that are dynamic at both ends. The
      control of polymer end stability is fundamental for the assembly and organization
      of cytoskeletal arrays, yet relatively little is understood about how microtubule
      minus ends are controlled in acentrosomal microtubule arrays, and no factors have
      been identified that act at the treadmilling minus ends in higher plants. Here,
      we identify Arabidopsis thaliana SPIRAL2 (SPR2) as a protein that tracks minus
      ends and protects them against subunit loss. SPR2 function is required to
      facilitate the rapid reorientation of plant cortical arrays as stimulated by
      light perception, a process that is driven by microtubule severing to create a
      new population of microtubules. Quantitative live-cell imaging and computer
      simulations reveal that minus protection by SPR2 acts by an unexpected mechanism
      to promote the lifetime of potential SPR2 severing sites, increasing the
      likelihood of severing and thus the rapid amplification of the new microtubule
      array.

PMID- 29339438
TI  - Quantifying exosome secretion from single cells reveals a modulatory role for
      GPCR signaling.
AB  - Exosomes are small endosome-derived extracellular vesicles implicated in cell
      cell communication and are secreted by living cells when multivesicular bodies
      (MVBs) fuse with the plasma membrane (PM). Current techniques to study exosome
      physiology are based on isolation procedures after secretion, precluding direct
      and dynamic insight into the mechanics of exosome biogenesis and the regulation
      of their release. In this study, we propose real-time visualization of MVB-PM
      fusion to overcome these limitations. We designed tetraspanin-based pH-sensitive
      optical reporters that detect MVB-PM fusion using live total internal reflection
      fluorescence and dynamic correlative light-electron microscopy. Quantitative
      analysis demonstrates that MVB-PM fusion frequency is reduced by depleting the
      target membrane SNAREs SNAP23 and syntaxin-4 but also can be induced in single
      cells by stimulation of the histamine H1 receptor (H1HR). Interestingly,
      activation of H1R1 in HeLa cells increases Ser110 phosphorylation of SNAP23,
      promoting MVB-PM fusion and the release of CD63-enriched exosomes. Using this
      single-cell resolution approach, we highlight the modulatory dynamics of MVB
      exocytosis that will help to increase our understanding of exosome physiology and
      identify druggable targets in exosome-associated pathologies.

PMID- 29339439
TI  - IDH1/2 Mutations Sensitize Acute Myeloid Leukemia to PARP Inhibition and This Is
      Reversed by IDH1/2-Mutant Inhibitors.
AB  - Purpose: Somatic mutations in IDH1/2 occur in approximately 20% of patients with
      myeloid neoplasms, including acute myeloid leukemia (AML). IDH1/2MUT enzymes
      produce D-2-hydroxyglutarate (D2HG), which associates with increased DNA damage
      and improved responses to chemo/radiotherapy and PARP inhibitors in solid tumor
      cells. Whether this also holds true for IDH1/2MUT AML is not known.Experimental
      Design: Well-characterized primary IDH1MUT, IDH2MUT, and IDH1/2WT AML cells were
      analyzed for DNA damage and responses to daunorubicin, ionizing radiation, and
      PARP inhibitors.Results:IDH1/2MUT caused increased DNA damage and sensitization
      to daunorubicin, irradiation, and the PARP inhibitors olaparib and talazoparib in
      AML cells. IDH1/2MUT inhibitors protected against these treatments. Combined
      treatment with a PARP inhibitor and daunorubicin had an additive effect on the
      killing of IDH1/2MUT AML cells. We provide evidence that the therapy sensitivity
      of IDH1/2MUT cells was caused by D2HG-mediated downregulation of expression of
      the DNA damage response gene ATM and not by altered redox responses due to
      metabolic alterations in IDH1/2MUT cells.Conclusions:IDH1/2MUT AML cells are
      sensitive to PARP inhibitors as monotherapy but especially when combined with a
      DNA-damaging agent, such as daunorubicin, whereas concomitant administration of
      IDH1/2MUT inhibitors during cytotoxic therapy decrease the efficacy of both
      agents in IDH1/2MUT AML. These results advocate in favor of clinical trials of
      PARP inhibitors either or not in combination with daunorubicin in IDH1/2MUT AML.
      Clin Cancer Res; 24(7); 1705-15. (c)2018 AACR.

PMID- 29339441
TI  - Allele-Specific Droplet Digital PCR Combined with a Next-Generation Sequencing
      Based Algorithm for Diagnostic Copy Number Analysis in Genes with High Homology:
      Proof of Concept Using Stereocilin.
AB  - BACKGROUND: Copy number variants (CNVs) can substantially contribute to the
      pathogenic variant spectrum in several disease genes. The detection of this type
      of variant is complicated in genes with high homology to other genomic sequences,
      yet such genomics regions are more likely to lead to CNVs, making it critical to
      address detection in these settings. METHODS: We developed a copy number analysis
      approach for high homology genes/regions that consisted of next-generation
      sequencing (NGS)-based dosage analysis accompanied by allele-specific droplet
      digital PCR (ddPCR) confirmatory testing. We applied this approach to copy number
      analysis in STRC, a gene with 98.9% homology to a nonfunctional pseudogene,
      pSTRC, and characterized its accuracy in detecting different copy number states
      by use of known samples. RESULTS: Using a cohort of 517 patients with hearing
      loss, we prospectively demonstrated the clinical utility of the approach, which
      contributed 30 of the 122 total positives (6%) to the diagnostic yield,
      increasing the overall yield from 17.6% to 23.6%. Positive STRC genotypes
      included homozygous (n = 15) or compound heterozygous (n = 8) deletions, or
      heterozygous deletions in trans with pathogenic sequence variants (n = 7).
      Finally, this approach limited ddPCR testing to cases with NGS copy number
      findings, thus markedly reducing the number of costly and laborious, albeit
      specific, ddPCR tests. CONCLUSIONS: NGS-based CNV detection followed by allele
      specific ddPCR confirmatory testing is a reliable and affordable approach for
      copy number analysis in medically relevant genes with homology issues.

PMID- 29339440
TI  - Repurposing Tin Mesoporphyrin as an Immune Checkpoint Inhibitor Shows Therapeutic
      Efficacy in Preclinical Models of Cancer.
AB  - Purpose: Unprecedented clinical outcomes have been achieved in a variety of
      cancers by targeting immune checkpoint molecules. This preclinical study
      investigates heme oxygenase-1 (HO-1), an immunosuppressive enzyme that is
      expressed in a wide variety of cancers, as a potential immune checkpoint target
      in the context of a chemotherapy-elicited antitumor immune response. We evaluate
      repurposing tin mesoporphyrin (SnMP), which has demonstrated safety and efficacy
      targeting hepatic HO in the clinic for the treatment of hyperbilirubinemia, as an
      immune checkpoint blockade therapy for the treatment of cancer.Experimental
      Design: SnMP and genetic inactivation of myeloid HO-1 were evaluated alongside 5
      fluorouracil in an aggressive spontaneous murine model of breast cancer (MMTV
      PyMT). Single-cell RNA sequencing analysis, tumor microarray, and clinical
      survival data from breast cancer patients were used to support the clinical
      relevance of our observations.Results: We demonstrate that SnMP inhibits immune
      suppression of chemotherapy-elicited CD8+ T cells by targeting myeloid HO-1
      activity in the tumor microenvironment. Microarray and survival data from breast
      cancer patients reveal that HO-1 is a poor prognostic factor in patients
      receiving chemotherapy. Single-cell RNA-sequencing analysis suggests that the
      myeloid lineage is a significant source of HO-1 expression, and is co-expressed
      with the immune checkpoints PD-L1/2 in human breast tumors. In vivo, we
      therapeutically compare the efficacy of targeting these two pathways alongside
      immune-stimulating chemotherapy, and demonstrate that the efficacy of SnMP
      compares favorably with PD-1 blockade in preclinical models.Conclusions: SnMP
      could represent a novel immune checkpoint therapy, which may improve the
      immunological response to chemotherapy. Clin Cancer Res; 24(7); 1617-28. (c)2018
      AACR.

PMID- 29339442
TI  - Specific Substrate for the Assay of Lysosomal Acid Lipase.
AB  - BACKGROUND: Deficiency of lysosomal acid lipase (LAL) causes Wolman disease and
      cholesterol ester storage disease. With the recent introduction of enzyme
      replacement therapy to manage LAL deficiency comes the need for a reliable assay
      of LAL enzymatic activity that can be applied to dried blood spots (DBS).
      METHODS: We prepared and tested a library of analogs of palmitoyl 4
      methylumbelifferyl esters to find a highly active and specific substrate for LAL
      in DBS. The LAL assay was optimized leading to both LC-MS/MS and fluorometric
      assay of LAL. We tested the new assay on DBS from healthy and LAL-deficient
      patients. RESULTS: The ester formed between palmitic acid and 4-propyl-8-methyl-7
      hydroxycoumarin (P-PMHC) was found to be >98% selective for LAL in DBS based on
      the sensitivity of its activity to the LAL-specific inactivator Lalistat-2 and
      the fact that the activity was close to zero using DBS from patients previously
      shown to be LAL-deficient. Use of P-PMHC and heavy isotope-labeled internal
      standard with optimized assay conditions led to an approximately 2-fold increase
      in the specific activity of LAL compared with the previously reported LAL assay.
      Patients deficient in LAL were readily distinguished from normal persons with the
      new LAL assay using UPLC-MS/MS or fluorometric assay platforms. CONCLUSIONS: The
      new assay can measure LAL in DBS with a single measurement compared with the
      previous method involving 2 assays done in parallel.

PMID- 29339443
TI  - Immune system: The "seventh sense".
AB  - The brain is our computing machine that integrates stimuli from the environment
      and orchestrates responses to these stimuli. Here, I propose that the defining
      role of the immune system is to sense microorganisms and to inform the brain
      about them.

PMID- 29339444
TI  - LIGHT-HVEM signaling in keratinocytes controls development of dermatitis.
AB  - Dermatitis is often associated with an allergic reaction characterized by
      excessive type 2 responses leading to epidermal acanthosis, hyperkeratosis, and
      dermal inflammation. Although factors like IL-4, IL-13, and thymic stromal
      lymphopoietin (TSLP) are thought to be instrumental for the development of this
      type of skin disorder, other cytokines may be critical. Here, we show that the
      tumor necrosis factor (TNF) superfamily protein LIGHT (homologous to lymphotoxin,
      exhibits inducible expression, and competes with HSV glycoprotein D for binding
      to HVEM, a receptor expressed on T lymphocytes) is required for experimental
      atopic dermatitis, and LIGHT directly controls keratinocyte hyperplasia, and
      production of periostin, a matricellular protein that contributes to the clinical
      features of atopic dermatitis as well as other skin diseases such as scleroderma.
      Mice with a conditional deletion of the LIGHT receptor HVEM (herpesvirus entry
      mediator) in keratinocytes phenocopied LIGHT-deficient mice in exhibiting reduced
      epidermal thickening and dermal collagen deposition in a model of atopic
      dermatitis driven by house dust mite allergen. LIGHT signaling through HVEM in
      human epidermal keratinocytes directly induced proliferation and periostin
      expression, and both keratinocyte-specific deletion of HVEM or antibody blocking
      of LIGHT-HVEM interactions after disease onset prevented expression of periostin
      and limited atopic dermatitis symptoms. Developing reagents that neutralize LIGHT
      HVEM signaling might be useful for therapeutic intervention in skin diseases
      where periostin is a central feature.

PMID- 29339445
TI  - Bile acids in glucose metabolism in health and disease.
AB  - Bile acids (BAs) are cholesterol-derived metabolites that facilitate the
      intestinal absorption and transport of dietary lipids. Recently, BAs also emerged
      as pivotal signaling molecules controlling glucose, lipid, and energy metabolism
      by binding to the nuclear hormone farnesoid X receptor (FXR) and Takeda G protein
      receptor 5 (TGR5) in multiple organs, leading to regulation of intestinal
      incretin secretion, hepatic gluconeogenesis, glycogen synthesis, energy
      expenditure, inflammation, and gut microbiome configuration. Alterations in BA
      metabolism and signaling are associated with obesity and type 2 diabetes mellitus
      (T2DM), whereas treatment of T2DM patients with BA sequestrants, or bariatric
      surgery in morbidly obese patients, results in a significant improvement in
      glycemic response that is associated with changes in the BA profile and
      signaling. Herein, we review the roles of BAs in glucose metabolism in health and
      disease; highlight the limitations, unknowns, and challenges in understanding the
      impact of BAs on the glycemic response; and discuss how this knowledge may be
      harnessed to develop innovative therapeutic approaches for the treatment of
      hyperglycemia and diabetes.

PMID- 29339446
TI  - Ontogeny of human mucosal-associated invariant T cells and related T cell
      subsets.
AB  - Mucosal-associated invariant T (MAIT) cells are semi-invariant Valpha7.2+
      CD161highCD4- T cells that recognize microbial riboflavin precursor derivatives
      such as 5-OP-RU presented by MR1. Human MAIT cells are abundant in adult blood,
      but there are very few in cord blood. We longitudinally studied Valpha7.2+
      CD161high T cell and related subset levels in infancy and after cord blood
      transplantation. We show that Valpha7.2+ and Valpha7.2- CD161high T cells are
      generated early during gestation and likely share a common prenatal developmental
      program. Among cord blood Valpha7.2+ CD161high T cells, the minority recognizing
      MR1:5-OP-RU display a TRAV/TRBV repertoire very similar to adult MAIT cells.
      Within a few weeks of life, only the MR1:5-OP-RU reactive Valpha7.2+ CD161high T
      cells acquire a memory phenotype. Only these cells expand to form the adult MAIT
      pool, diluting out other Valpha7.2+ CD161high and Valpha7.2- CD161high
      populations, in a process requiring at least 6 years to reach adult levels. Thus,
      the high clonal size of adult MAIT cells is antigen-driven and likely due to the
      fine specificity of the TCRalphabeta chains recognizing MR1-restricted microbial
      antigens.

PMID- 29339447
TI  - Guidance of super-enhancers in regulation of IL-9 induction and airway
      inflammation.
AB  - Th9 cells are prominently featured in allergic lung inflammation, but the
      mechanism that regulates IL-9 induction in T helper cells remains poorly defined.
      Here we demonstrate that formation of super-enhancers (SEs) is critical in robust
      induction of IL-9 and that assembly of the Il9 SEs in Th cells requires OX40
      triggered chromatin acetylation. Mechanistically, we found that OX40
      costimulation induces RelB expression, which recruits the histone
      acetyltransferase p300 to the Il9 locus to catalyze H3K27 acetylation. This
      allows binding of the SE factor Brd4 to organize assembly of the SE complex,
      which in turn drives robust IL-9 expression and Th9 cell induction. Thus, Th9
      cells are strongly induced upon OX40 stimulation, and disruption of SEs abolished
      Th9 cell induction in vitro and inhibited Th9 cell-mediated allergic airway
      inflammation in vivo. Together, our data suggest that formation of SEs is
      essential in IL-9 expression and Th9 cell induction. These findings may have
      important clinical implications.

PMID- 29339448
TI  - Development of intestinal M cells and follicle-associated epithelium is regulated
      by TRAF6-mediated NF-kappaB signaling.
AB  - M cells are located in the follicle-associated epithelium (FAE) that covers
      Peyer's patches (PPs) and are responsible for the uptake of intestinal antigens.
      The differentiation of M cells is initiated by receptor activator of NF-kappaB.
      However, the intracellular pathways involved in M cell differentiation are still
      elusive. In this study, we demonstrate that the NF-kappaB pathway activated by
      RANK is essential for M cell differentiation using in vitro organoid culture.
      Overexpression of NF-kappaB transcription factors enhances the expression of M
      cell-associated molecules but is not sufficient to complete M cell
      differentiation. Furthermore, we evaluated the requirement for tumor necrosis
      factor receptor-associated factor 6 (TRAF6). Conditional deletion of TRAF6 in the
      intestinal epithelium causes a complete loss of M cells in PPs, resulting in
      impaired antigen uptake into PPs. In addition, the expression of FAE-associated
      genes is almost silenced in TRAF6-deficient mice. This study thus demonstrates
      the crucial role of TRAF6-mediated NF-kappaB signaling in the development of M
      cells and FAE.

PMID- 29339449
TI  - Targeting IRF3 as a YAP agonist therapy against gastric cancer.
AB  - The Hippo pathway plays a vital role in tissue homeostasis and tumorigenesis. The
      transcription factor IRF3 is essential for innate antiviral immunity. In this
      study, we discovered IRF3 as an agonist of Yes-associated protein (YAP). The
      expression of IRF3 is positively correlated with that of YAP and its target genes
      in gastric cancer; the expression of both IRF3 and YAP is up-regulated and
      prognosticates patient survival. IRF3 interacts with both YAP and TEAD4 in the
      nucleus to enhance their interaction, promoting nuclear translocation and
      activation of YAP. IRF3 and YAP-TEAD4 are associated genome-wide to cobind and
      coregulate many target genes of the Hippo pathway. Overexpression of active IRF3
      increased, but depletion of IRF3 reduced, the occupancy of YAP on the target
      genes. Knockdown or pharmacological targeting of IRF3 by Amlexanox, a drug used
      clinically for antiinflammatory treatment, inhibits gastric tumor growth in a YAP
      dependent manner. Collectively, our study identifies IRF3 as a positive regulator
      for YAP, highlighting a new therapeutic target against YAP-driven cancers.

PMID- 29339451
TI  - Inhibition of 5alpha-reductase alters pregnane metabolism in the late pregnant
      mare.
AB  - In the latter half of gestation in the mare, progesterone concentrations decline
      to near undetectable levels while other 5alpha-reduced pregnanes are elevated. Of
      these, 5alpha-dihydroprogesterone and allopregnanolone have been reported to have
      important roles in either pregnancy maintenance or fetal quiescence. During this
      time, the placenta is necessary for pregnane metabolism, with the enzyme 5alpha
      reductase being required for the conversion of progesterone to 5alpha
      dihydroprogesterone. The objectives of this study were to assess the effects of a
      5alpha-reductase inhibitor, dutasteride on pregnane metabolism (pregnenolone,
      progesterone, 5alpha-dihydroprogesterone, 20alpha-hydroxy-5alpha-pregnan-3-one,
      5alpha-pregnane-3beta,20alpha-diol and allopregnanolone), to determine
      circulating dutasteride concentrations and to assess effects of dutasteride
      treatment on gestational parameters. Pregnant mares (n = 5) received dutasteride
      (0.01 mg/kg/day, IM) and control mares (n = 4) received vehicle alone from 300 to
      320 days of gestation or until parturition. Concentrations of dutasteride,
      pregnenolone, progesterone, 5alpha-dihydroprogesterone, 20alpha-hydroxy-5alpha
      pregnan-3-one, 5alpha-pregnane-3beta,20alpha-diol, and allopregnanolone were
      evaluated via liquid chromatography-tandem mass spectrometry. Samples were
      analyzed as both days post treatment and as days prepartum. No significant
      treatment effects were detected in pregnenolone, 5alpha-dihydroprogesterone,
      20alpha-hydroxy-5alpha-pregnan-3-one, 5alpha-pregnane-3beta,20alpha-diol or
      allopregnanolone for either analysis; however, progesterone concentrations were
      increased (P < 0.05) sixfold in dutasteride-treated mares compared to control
      mares. Dutasteride concentrations increased in the treated mares, with a
      significant correlation (P < 0.05) between dutasteride concentrations and
      pregnenolone or progesterone concentrations. Gestational length and neonatal
      outcomes were not significantly altered in dutasteride-treated mares. Although
      5alpha-reduced metabolites were unchanged, these data suggest an accumulation of
      precursor progesterone with inhibition of 5alpha-reductase, indicating the
      ability of dutasteride to alter progesterone metabolism.

PMID- 29339450
TI  - Cardiac macrophages promote diastolic dysfunction.
AB  - Macrophages populate the healthy myocardium and, depending on their phenotype,
      may contribute to tissue homeostasis or disease. Their origin and role in
      diastolic dysfunction, a hallmark of cardiac aging and heart failure with
      preserved ejection fraction, remain unclear. Here we show that cardiac
      macrophages expand in humans and mice with diastolic dysfunction, which in mice
      was induced by either hypertension or advanced age. A higher murine myocardial
      macrophage density results from monocyte recruitment and increased hematopoiesis
      in bone marrow and spleen. In humans, we observed a parallel constellation of
      hematopoietic activation: circulating myeloid cells are more frequent, and
      splenic 18F-FDG PET/CT imaging signal correlates with echocardiographic indices
      of diastolic dysfunction. While diastolic dysfunction develops, cardiac
      macrophages produce IL-10, activate fibroblasts, and stimulate collagen
      deposition, leading to impaired myocardial relaxation and increased myocardial
      stiffness. Deletion of IL-10 in macrophages improves diastolic function. These
      data imply expansion and phenotypic changes of cardiac macrophages as therapeutic
      targets for cardiac fibrosis leading to diastolic dysfunction.

PMID- 29339452
TI  - Effects of colostrum, feeding method and oral IGF1 on porcine uterine
      development.
AB  - Nursing ensures lactocrine delivery of maternally derived, milk-borne bioactive
      factors to offspring, which affects postnatal development of female reproductive
      tract tissues. Disruption of lactocrine communication for two days from birth
      (postnatal day (PND) 0) by feeding milk replacer in lieu of nursing or
      consumption of colostrum alters porcine uterine gene expression globally by PND 2
      and inhibits uterine gland genesis by PND 14. Here, objectives were to determine
      effects of: (1) nursing or milk replacer feeding from birth; (2) a single dose of
      colostrum or milk replacer and method of feeding and (3) a single feeding of
      colostrum or milk replacer, with or without oral supplementation of IGF1,
      administered at birth on aspects of porcine uterine development at 12-h
      postnatally. Results indicate nursing for 12 h from birth supports rapid
      establishment of a uterine developmental program, illustrated by patterns of
      endometrial cell proliferation, expression of genes associated with uterine wall
      development and entry into mitosis and establishment of a uterine MMP9/TIMP1
      system. A single feeding of colostrum at birth increased endometrial cell
      proliferation at 12 h, regardless of method of feeding. Oral supplementation of
      IGF1 was sufficient to support endometrial cell proliferation at 12 h in replacer
      fed gilts, and supplementation of colostrum with IGF1 further increased
      endometrial cell proliferation. Results indicate that lactocrine regulation of
      postnatal uterine development is initiated with the first ingestion of colostrum.
      Further, results suggest IGF1 may be lactocrine-active and support a 12-h
      bioassay, which can be used to identify uterotrophic lactocrine activity.

PMID- 29339453
TI  - PGRMC1 localization and putative function in the nucleolus of bovine granulosa
      cells and oocytes.
AB  - Progesterone receptor membrane component-1 (PGRMC1) is a highly conserved
      multifunctional protein that is found in numerous systems, including reproductive
      system. Interestingly, PGRMC1 is expressed at several intracellular locations,
      including the nucleolus. The aim of this study is to investigate the functional
      relationship between PGRMC1 and nucleolus. Immunofluorescence experiments
      confirmed PGRMC1's nucleolar localization in cultured bovine granulosa cells
      (bGC) and oocytes. Additional experiments conducted on bGC revealed that PGRMC1
      co-localizes with nucleolin (NCL), a major nucleolar protein. Furthermore, small
      interfering RNA (RNAi)-mediated gene silencing experiments showed that when
      PGRMC1 expression was depleted, NCL translocated from the nucleolus to the
      nucleoplasm. Similarly, oxidative stress induced by hydrogen peroxide (H2O2)
      treatment, reduced PGRMC1 immunofluorescent signal in the nucleolus and increased
      NCL nucleoplasmic signal, when compared to non-treated cells. Although PGRMC1
      influenced NCL localization, a direct interaction between these two proteins was
      not detected using in situ proximity ligation assay. This suggests the
      involvement of additional molecules in mediating the co-localization of PGRMC1
      and nucleolin. Since nucleolin translocates into the nucleoplasm in response to
      various cellular stressors, PGRMC1's ability to regulate its localization within
      the nucleolus is likely an important component of mechanism by which cells
      response to stress. This concept is consistent with PGRMC1's well-described
      ability to promote ovarian cell survival and provides a rationale for future
      studies on PGRMC1, NCL and the molecular mechanism by which these two proteins
      protect against the adverse effect of cellular stressors, including oxidative
      stress.

PMID- 29339454
TI  - Chromatin remodeling in mammalian embryos.
AB  - The mammalian embryo undergoes a dramatic amount of epigenetic remodeling during
      the first week of development. In this review, we discuss several epigenetic
      changes that happen over the course of cleavage development, focusing on covalent
      marks (e.g., histone methylation and acetylation) and non-covalent remodeling
      (chromatin remodeling via remodeling complexes; e.g., SWI/SNF-mediated chromatin
      remodeling). Comparisons are also drawn between remodeling events that occur in
      embryos from a variety of mammalian species.

PMID- 29339455
TI  - High N-Acetyltransferase 1  Expression Is Associated with Estrogen Receptor
      Expression in Breast Tumors, but Is not Under Direct Regulation by Estradiol,
      5alpha-androstane-3beta,17beta-Diol, or Dihydrotestosterone in Breast Cancer
      Cells.
AB  - N-acetyltransferase 1 (NAT1) is an enzyme that metabolizes carcinogens, which
      suggests a potential role in breast carcinogenesis. High NAT1 expression in
      breast tumors is associated with estrogen receptor alpha (ERalpha+) and the
      luminal subtype. We report that NAT1 mRNA transcript, protein, and enzyme
      activity were higher in human breast tumors with high expression of ERalpha/ESR1
      compared with normal breast tissue. There was a strong correlation between NATb
      promoter and NAT1 protein expression/enzyme activity. High NAT1 expression in
      tumors was not the result of adipocytes, as evidenced by low perilipin (PLIN)
      expression. ESR1, NAT1, and XBP1 expression were associated in tumor biopsies.
      Direct regulation of NAT1 transcription by estradiol (E2) was investigated in
      ERalpha (+) MCF-7 and T47D breast cancer cells. E2 did not increase NAT1
      transcript expression but increased progesterone receptor expression in a dose
      dependent manner. Likewise, NAT1 transcript levels were not increased by
      dihydrotestosterone (DHT) or 5alpha-androstane-3beta, (3beta-adiol) 17beta-diol.
      Dithiothreitol increased levels of the activated, spliced XBP1 in ERalpha (+) MCF
      7 and T47D breast cancer cells but did not affect NAT1 or ESR1 expression. We
      conclude that NAT1 expression is not directly regulated by E2, DHT, 3beta-adiol,
      or dithiothreitol despite high NAT1 and ESR1 expression in luminal A breast
      cancer cells, suggesting that ESR1, XBP1, and NAT1 expression may share a common
      transcriptional network arising from the luminal epithelium associated with
      better survival in breast cancer. Clusters of high-expression genes, including
      NAT1, in breast tumors might serve as potential targets for novel therapeutic
      drug development.

PMID- 29339456
TI  - PARP Inhibition Prevents Ethanol-Induced Neuroinflammatory Signaling and
      Neurodegeneration in Rat Adult-Age Brain Slice Cultures.
AB  - Using rat adult-age hippocampal-entorhinal cortical (HEC) slice cultures, we
      examined the role of poly [ADP-ribose] polymerase (PARP) in binge ethanol's brain
      inflammatory and neurodegenerative mechanisms. Activated by DNA strand breaks,
      PARP (principally PARP1 in the brain) promotes DNA repair via poly [ADP-ribose]
      (PAR) products, but PARP overactivation triggers regulated neuronal necrosis
      (e.g., parthanatos). Previously, we found that brain PARP1 levels were
      upregulated by neurotoxic ethanol binges in adult rats and HEC slices, and PARP
      inhibitor PJ34 abrogated slice neurodegeneration. Binged HEC slices also
      exhibited increased Ca+2-dependent phospholipase A2 (PLA2) isoenzymes (cPLA2 IVA
      and sPLA2 IIA) that mobilize proinflammatory omega6 arachidonic acid (ARA). We
      now find in 4-day-binged HEC slice cultures (100 mM ethanol) that PARP1
      elevations after two overnight binges precede PAR, cPLA2, and sPLA2 enhancements
      by 1 day and high-mobility group box-1 (HMGB1), an ethanol-responsive alarmin
      that augments proinflammatory cytokines via toll-like receptor-4 (TLR4), by 2
      days. After verifying that PJ34 effectively blocks PARP activity (?PAR), we
      demonstrated that, like PJ34, three other PARP inhibitors-olaparib, veliparib,
      and 4-aminobenzamide-provided neuroprotection from ethanol. Importantly, PJ34 and
      olaparib also prevented ethanol's amplification of the PLA2 isoenzymes, and two
      PLA2 inhibitors were neuroprotective-thus coupling PARP to PLA2, with PLA2
      activity promoting neurodegeneration. Also, PJ34 and olaparib blocked ethanol
      induced HMGB1 elevations, linking brain PARP induction to TLR4 activation. The
      results provide evidence in adult brains that induction of PARP1 may mediate dual
      neuroinflammatory pathways (PLA2->phospholipid->ARA and HMGB1->TLR4
      >proinflammatory cytokines) that are complicit in binge ethanol-induced
      neurodegeneration.

PMID- 29339457
TI  - Curcumin Acts as a Positive Allosteric Modulator of alpha7-Nicotinic
      Acetylcholine Receptors and Reverses Nociception in Mouse Models of Inflammatory
      Pain.
AB  - Effects of curcumin, a major ingredient of turmeric, were tested on the function
      of the alpha7-subunit of the human nicotinic acetylcholine (alpha7-nACh) receptor
      expressed in Xenopus oocytes and on nociception in mouse models of tonic and
      visceral pain. Curcumin caused a significant potentiation of currents induced by
      acetylcholine (ACh; 100 MUM) with an EC50 value of 0.2 uM. The effect of curcumin
      was not dependent on the activation of G-proteins and protein kinases and did not
      involve Ca2+-dependent Cl- channels expressed endogenously in oocytes.
      Importantly, the extent of curcumin potentiation was enhanced significantly by
      decreasing ACh concentrations. Curcumin did not alter specific binding of
      [125I]alpha-bungarotoxin. In addition, curcumin attenuated nociceptive behavior
      in both tonic and visceral pain models without affecting motor and locomotor
      activity and without producing tolerance. Pharmacological and genetic approaches
      revealed that the antinociceptive effect of curcumin was mediated by alpha7-nACh
      receptors. Curcumin potentiated the antinociceptive effects of the alpha7-nACh
      receptor agonist N-(3R)-1-azabicyclo[2.2.2]oct-3-yl-4-chlorobenzamide
      (PNU282987). Collectively, our results indicate that curcumin is a positive
      allosteric modulator of alpha7-nACh receptor and reverses nociception in mouse
      models of tonic and visceral pain.

PMID- 29339458
TI  - Coassociation between Group B Streptococcus and Candida albicans Promotes
      Interactions with Vaginal Epithelium.
AB  - Group B Streptococcus (GBS) is a leading cause of neonatal sepsis, pneumonia, and
      meningitis worldwide. In the majority of cases, GBS is transmitted vertically
      from mother to neonate, making maternal vaginal colonization a key risk factor
      for neonatal disease. The fungus Candida albicans is an opportunistic pathogen of
      the female genitourinary tract and the causative agent of vaginal thrush.
      Carriage of C. albicans has been shown to be an independent risk factor for
      vaginal colonization by GBS. However, the nature of interactions between these
      two microbes is poorly understood. This study provides evidence of a reciprocal,
      synergistic interplay between GBS and C. albicans that may serve to promote their
      cocolonization of the vaginal mucosa. GBS strains NEM316 (serotype III) and 515
      (serotype Ia) are shown to physically interact with C. albicans, with the
      bacteria exhibiting tropism for candidal hyphal filaments. This interaction
      enhances association levels of both microbes with the vaginal epithelial cell
      line VK2/E6E7. The ability of GBS to coassociate with C. albicans is dependent
      upon expression of the hypha-specific adhesin Als3. In turn, expression of GBS
      antigen I/II family adhesins (Bsp polypeptides) facilitates this coassociation
      and confers upon surrogate Lactococcus lactis the capacity to exhibit enhanced
      interactions with C. albicans on vaginal epithelium. As genitourinary tract
      colonization is an essential first step in the pathogenesis of GBS and C.
      albicans, the coassociation mechanism reported here may have important
      implications for the risk of disease involving both of these pathogens.

PMID- 29339459
TI  - Novel Two-Component System of Streptococcus sanguinis Affecting Functions
      Associated with Viability in Saliva and Biofilm Formation.
AB  - Streptococcus sanguinis is a pioneer species of teeth and a common opportunistic
      pathogen of infective endocarditis. In this study, we identified a two-component
      system, S. sanguinis SptRS (SptRS Ss ), affecting S. sanguinis survival in saliva
      and biofilm formation. Isogenic mutants of sptRSs (SKsptR) and sptSSs (SKsptS)
      showed reduced cell counts in ex vivo assays of viability in saliva compared to
      those of parent strain SK36 and complemented mutants. Reduced counts of the
      mutants in saliva were associated with reduced growth rates in nutrient-poor
      medium (RPMI) and increased susceptibility to the deposition of C3b and the
      membrane attach complex (MAC) of the complement system, a defense component of
      saliva and serum. Conversely, sptRSs and sptSSs mutants showed increased biofilm
      formation associated with higher levels of production of H2O2 and extracellular
      DNA. Reverse transcription-quantitative PCR (RT-qPCR) comparisons of strains
      indicated a global role of SptRS Ss in repressing genes for H2O2 production (2.5-
      to 15-fold upregulation of spxB, spxR, vicR, tpk, and ackA in sptRSs and sptSSs
      mutants), biofilm formation, and/or evasion of host immunity (2.1- to 11.4-fold
      upregulation of srtA, pcsB, cwdP, iga, and nt5e). Compatible with the homology of
      SptR Ss with AraC-type regulators, duplicate to multiple conserved repeats were
      identified in 1,000-bp regulatory regions of downstream genes, suggesting that
      SptR Ss regulates transcription by DNA looping. Significant transcriptional
      changes in the regulatory genes vicR, spxR, comE, comX, and mecA in the sptRSs
      and sptSSs mutants further indicated that SptRS Ss is part of a regulatory
      network that coordinates cell wall homeostasis, H2O2 production, and competence.
      This study reveals that SptRS Ss is involved in the regulation of crucial
      functions for S. sanguinis persistence in the oral cavity.

PMID- 29339460
TI  - Dot/Icm-Translocated Proteins Important for Biogenesis of the Coxiella burnetii
      Containing Vacuole Identified by Screening of an Effector Mutant Sublibrary.
AB  - Coxiella burnetii is an intracellular pathogen that replicates in a lysosome
      derived vacuole. A determinant necessary for C. burnetii virulence is the Dot/Icm
      type IVB secretion system (T4SS). The Dot/Icm system delivers more than 100
      proteins, called type IV effectors (T4Es), across the vacuolar membrane into the
      host cell cytosol. Several T4Es have been shown to be important for vacuolar
      biogenesis. Here, transposon (Tn) insertion sequencing technology (INSeq) was
      used to identify C. burnetii Nine Mile phase II mutants in an arrayed library,
      which facilitated the identification and clonal isolation of mutants deficient in
      70 different T4E proteins. These effector mutants were screened in HeLa cells for
      deficiencies in Coxiella-containing vacuole (CCV) biogenesis. This screen
      identified and validated seven new T4Es that were important for vacuole
      biogenesis. Loss-of-function mutations in cbu0414 (coxH1), cbu0513, cbu0978
      (cem3), cbu1387 (cem6), cbu1524 (caeA), cbu1752, or cbu2028 resulted in a small
      vacuole phenotype. These seven mutant strains produced small CCVs in all cells
      tested, which included macrophage-like cells. The cbu2028::Tn mutant, though
      unable to develop large CCVs, had intracellular replication rates similar to the
      rate of the parental strain of C. burnetii, whereas the other six effector
      mutants defective in CCV biogenesis displayed significant reductions in
      intracellular replication. Vacuoles created by the cbu0513::Tn mutant did not
      accumulate lipidated microtubule-associated protein 1A/1B light chain 3 (LC3-II),
      suggesting a failure in fusion of the CCV with autophagosomes. These seven T4E
      proteins add to the growing repertoire of C. burnetii factors that contribute to
      CCV biogenesis.

PMID- 29339461
TI  - Cooperative Immune Suppression by Escherichia coli and Shigella Effector
      Proteins.
AB  - The enteric attaching and effacing (A/E) pathogens enterohemorrhagic Escherichia
      coli (EHEC) and enteropathogenic E. coli (EPEC) and the invasive pathogens
      enteroinvasive E. coli (EIEC) and Shigella encode type III secretion systems
      (T3SS) used to inject effector proteins into human host cells during infection.
      Among these are a group of effectors required for NF-kappaB-mediated host immune
      evasion. Recent studies have identified several effector proteins from A/E
      pathogens and EIEC/Shigella that are involved in suppression of NF-kappaB and
      have uncovered their cellular and molecular functions. A novel mechanism among
      these effectors from both groups of pathogens is to coordinate effector function
      during infection. This cooperativity among effector proteins explains how
      bacterial pathogens are able to effectively suppress innate immune defense
      mechanisms in response to diverse classes of immune receptor signaling complexes
      (RSCs) stimulated during infection.

PMID- 29339462
TI  - Direct Manipulation of T Lymphocytes by Proteins of Gastrointestinal Bacterial
      Pathogens.
AB  - Gastrointestinal bacterial infection represents a significant threat to human
      health, as well as a burden on food animal production and welfare. Although there
      is advanced knowledge about the molecular mechanisms underlying pathogenesis,
      including the development of immune responses to these pathogens, gaps in
      knowledge persist. It is well established that gastrointestinal bacterial
      pathogens produce a myriad of proteins that affect the development and
      effectiveness of innate immune responses. However, relatively few proteins that
      directly affect lymphocytes responsible for humoral or cell-mediated immunity and
      memory have been identified. Here, we review factors produced by gastrointestinal
      bacterial pathogens that have direct T cell interactions and what is known about
      their functions and mechanisms of action. T cell-interacting bacterial proteins
      that have been identified to date mainly target three major T cell responses:
      activation and expansion, chemotaxis, or apoptosis. Further, the requirement for
      more focused studies to identify and understand additional mechanisms used by
      bacteria to directly affect the T cell immune response and how these may
      contribute to pathogenesis is highlighted. Increased knowledge in this area will
      help to drive development of better interventions in prevention and treatment of
      gastrointestinal bacterial infection.

PMID- 29339463
TI  - Cell Cycle Arrest and Apoptosis Induced by Porphyromonas gingivalis Require Jun N
      Terminal Protein Kinase- and p53-Mediated p38 Activation in Human Trophoblasts.
AB  - Porphyromonas gingivalis, a periodontal pathogen, has been implicated as a
      causative agent of preterm delivery of low-birth-weight infants. We previously
      reported that P. gingivalis activated cellular DNA damage signaling pathways and
      ERK1/2 that lead to G1 arrest and apoptosis in extravillous trophoblast cells
      (HTR-8 cells) derived from the human placenta. In the present study, we further
      examined alternative signaling pathways mediating cellular damage caused by P.
      gingivalis. P. gingivalis infection of HTR-8 cells induced phosphorylation of p38
      and Jun N-terminal protein kinase (JNK), while their inhibitors diminished both
      G1 arrest and apoptosis. In addition, heat shock protein 27 (HSP27) was
      phosphorylated through both p38 and JNK, and knockdown of HSP27 with small
      interfering RNA (siRNA) prevented both G1 arrest and apoptosis. Furthermore,
      regulation of G1 arrest and apoptosis was associated with p21 expression. HTR-8
      cells infected with P. gingivalis exhibited upregulation of p21, which was
      regulated by p53 and HSP27. These results suggest that P. gingivalis induces G1
      arrest and apoptosis via novel molecular pathways that involve p38 and JNK with
      its downstream effectors in human trophoblasts.

PMID- 29339467
TI  - Profile of Scott W. Lowe.

PMID- 29339464
TI  - Propionate enters GABAergic neurons, inhibits GABA transaminase, causes GABA
      accumulation and lethargy in a model of propionic acidemia.
AB  - Propionic acidemia is the accumulation of propionate in blood due to dysfunction
      of propionyl-CoA carboxylase. The condition causes lethargy and striatal
      degeneration with motor impairment in humans. How propionate exerts its toxic
      effect is unclear. Here, we show that intravenous administration of propionate
      causes dose-dependent propionate accumulation in the brain and transient lethargy
      in mice. Propionate, an inhibitor of histone deacetylase, entered GABAergic
      neurons, as could be seen from increased neuronal histone H4 acetylation in the
      striatum and neocortex. Propionate caused an increase in GABA (gamma-amino
      butyric acid) levels in the brain, suggesting inhibition of GABA breakdown. In
      vitro propionate inhibited GABA transaminase with a Ki of ~1 mmol/l. In isolated
      nerve endings, propionate caused increased release of GABA to the extracellular
      fluid. In vivo, propionate reduced cerebral glucose metabolism in both striatum
      and neocortex. We conclude that propionate-induced inhibition of GABA
      transaminase causes accumulation of GABA in the brain, leading to increased
      extracellular GABA concentration, which inhibits neuronal activity and causes
      lethargy. Propionate-mediated inhibition of neuronal GABA transaminase, an enzyme
      of the inner mitochondrial membrane, indicates entry of propionate into neuronal
      mitochondria. However, previous work has shown that neurons are unable to
      metabolize propionate oxidatively, leading us to conclude that propionyl-CoA
      synthetase is probably absent from neuronal mitochondria. Propionate-induced
      inhibition of energy metabolism in GABAergic neurons may render the striatum, in
      which >90% of the neurons are GABAergic, particularly vulnerable to degeneration
      in propionic acidemia.

PMID- 29339468
TI  - Molecular epidemiology reveals the role of war in the spread of HIV in Ukraine.
AB  - Ukraine has one of the largest HIV epidemics in Europe, historically driven by
      people who inject drugs (PWID). The epidemic showed signs of stabilization in
      2012, but the recent war in eastern Ukraine may be reigniting virus spread. We
      investigated the movement of HIV-infected people within Ukraine before and during
      the conflict. We analyzed HIV-1 subtype-A pol nucleotide sequences sampled during
      2012-2015 from 427 patients of 24 regional AIDS centers and used phylogeographic
      analysis to reconstruct virus movement among different locations in Ukraine. We
      then tested for correlations between reported PWID behaviors and reconstructed
      patterns of virus spread. Our analyses suggest that Donetsk and Lugansk, two
      cities not controlled by the Ukrainian government in eastern Ukraine, were
      significant exporters of the virus to the rest of the country. Additional
      analyses showed that viral dissemination within the country changed after 2013.
      Spearman correlation analysis showed that incoming virus flow was correlated with
      the number of HIV-infected internally displaced people. Additionally, there was a
      correlation between more intensive virus movement and locations with a higher
      proportion of PWID practicing risky sexual behaviors. Our findings suggest that
      effective prevention responses should involve internally displaced people and
      people who frequently travel to war-affected regions. Scale-up of harm reduction
      services for PWID will be an important factor in preventing new local HIV
      outbreaks in Ukraine.

PMID- 29339470
TI  - A randomized controlled design reveals barriers to citizenship for low-income
      immigrants.
AB  - Citizenship endows legal protections and is associated with economic and social
      gains for immigrants and their communities. In the United States, however,
      naturalization rates are relatively low. Yet we lack reliable knowledge as to
      what constrains immigrants from applying. Drawing on data from a public/private
      naturalization program in New York, this research provides a randomized
      controlled study of policy interventions that address these constraints. The
      study tested two programmatic interventions among low-income immigrants who are
      eligible for citizenship. The first randomly assigned a voucher that covers the
      naturalization application fee among immigrants who otherwise would have to pay
      the full cost of the fee. The second randomly assigned a set of behavioral
      nudges, similar to outreach efforts used by service providers, among immigrants
      whose incomes were low enough to qualify them for a federal waiver that
      eliminates the application fee. Offering the fee voucher increased naturalization
      application rates by about 41%, suggesting that application fees act as a barrier
      for low-income immigrants who want to become US citizens. The nudges to encourage
      the very poor to apply had no discernible effect, indicating the presence of
      nonfinancial barriers to naturalization.

PMID- 29339469
TI  - The Bardet-Biedl syndrome protein complex is an adapter expanding the cargo range
      of intraflagellar transport trains for ciliary export.
AB  - Bardet-Biedl syndrome (BBS) is a ciliopathy resulting from defects in the BBSome,
      a conserved protein complex. BBSome mutations affect ciliary membrane
      composition, impairing cilia-based signaling. The mechanism by which the BBSome
      regulates ciliary membrane content remains unknown. Chlamydomonas bbs mutants
      lack phototaxis and accumulate phospholipase D (PLD) in the ciliary membrane.
      Single particle imaging revealed that PLD comigrates with BBS4 by intraflagellar
      transport (IFT) while IFT of PLD is abolished in bbs mutants. BBSome deficiency
      did not alter the rate of PLD entry into cilia. Membrane association and the N
      terminal 58 residues of PLD are sufficient and necessary for BBSome-dependent
      transport and ciliary export. The replacement of PLD's ciliary export sequence
      (CES) caused PLD to accumulate in cilia of cells with intact BBSomes and IFT. The
      buildup of PLD inside cilia impaired phototaxis, revealing that PLD is a negative
      regulator of phototactic behavior. We conclude that the BBSome is a cargo adapter
      ensuring ciliary export of PLD on IFT trains to regulate phototaxis.

PMID- 29339471
TI  - Laminar recordings in frontal cortex suggest distinct layers for maintenance and
      control of working memory.
AB  - All of the cerebral cortex has some degree of laminar organization. These
      different layers are composed of neurons with distinct connectivity patterns,
      embryonic origins, and molecular profiles. There are little data on the laminar
      specificity of cognitive functions in the frontal cortex, however. We recorded
      neuronal spiking/local field potentials (LFPs) using laminar probes in the
      frontal cortex (PMd, 8A, 8B, SMA/ACC, DLPFC, and VLPFC) of monkeys performing
      working memory (WM) tasks. LFP power in the gamma band (50-250 Hz) was strongest
      in superficial layers, and LFP power in the alpha/beta band (4-22 Hz) was
      strongest in deep layers. Memory delay activity, including spiking and stimulus
      specific gamma bursting, was predominately in superficial layers. LFPs from
      superficial and deep layers were synchronized in the alpha/beta bands. This was
      primarily unidirectional, with alpha/beta bands in deep layers driving
      superficial layer activity. The phase of deep layer alpha/beta modulated
      superficial gamma bursting associated with WM encoding. Thus, alpha/beta rhythms
      in deep layers may regulate the superficial layer gamma bands and hence
      maintenance of the contents of WM.

PMID- 29339472
TI  - miRNA-mediated targeting of human cytomegalovirus reveals biological host and
      viral targets of IE2.
AB  - Human cytomegalovirus (HCMV) impacts more than one-half of the human population
      owing to its capacity to manipulate the cell and create latent reservoirs in the
      host. Despite an extensive understanding of HCMV biology during acute infection
      in fibroblasts, the molecular basis for latency in myeloid cells remains
      incomplete. This knowledge gap is due largely to the fact that the existing
      genetic systems require virus rescue in fibroblasts, precluding the study of
      genes that are essential during acute infection, yet likely play unique roles in
      myeloid cells or the establishment of latency. Here we present a solution to
      address this restriction. Through the exploitation of a hematopoietic-specific
      microRNA, we demonstrate a one-step recombineering approach that enables gene
      silencing only in cells associated with latency. As a proof of concept, here we
      describe a TB40/E variant that undergoes hematopoietic targeting of the Immediate
      Early-2 (IE2) gene to explore its function during infection of myeloid cells.
      While virus replication of the hematopoietic-targeted IE2 variant was unimpaired
      in fibroblasts, we observed a >100-fold increase in virus titers in myeloid
      cells. Virus replication in myeloid cells demonstrated that IE2 has a significant
      transcriptional footprint on both viral and host genes. These data implicate IE2
      as an essential mediator of virus biology in myeloid cells and illustrate the
      utility of cell-specific microRNA-based targeting.

PMID- 29339473
TI  - Identification of thioredoxin-interacting protein (TXNIP) as a downstream target
      for IGF1 action.
AB  - Laron syndrome (LS), or primary growth hormone (GH) insensitivity, is the best
      characterized entity among the congenital insulin-like growth factor 1 (IGF1)
      deficiencies. Life-long exposure to minute endogenous IGF1 levels is linked to
      low stature as well as a number of endocrine and metabolic abnormalities. While
      elevated IGF1 is correlated with increased cancer incidence, epidemiological
      studies revealed that patients with LS do not develop tumors. The mechanisms
      associated with cancer protection in LS are yet to be discovered. Recent genomic
      analyses identified a series of metabolic genes that are overrepresented in
      patients with LS. Given the augmented expression of these genes in a low IGF1
      milieu, we hypothesized that they may constitute targets for IGF1 action.
      Thioredoxin-interacting protein (TXNIP) plays a critical role in cellular redox
      control by thioredoxin. TXNIP serves as a glucose and oxidative stress sensor,
      being commonly silenced by genetic or epigenetic events in cancer cells.
      Consistent with its enhanced expression in LS, we provide evidence that TXNIP
      gene expression is negatively regulated by IGF1. These results were corroborated
      in animal studies. In addition, we show that oxidative and glucose stresses led
      to marked increases in TXNIP expression. Supplementation of IGF1 attenuated TXNIP
      levels, suggesting that IGF1 exerts its antiapoptotic effect via inhibition of
      TXNIP Augmented TXNIP expression in LS may account for cancer protection in this
      condition. Finally, TXNIP levels could be potentially useful in the clinic as a
      predictive or diagnostic biomarker for IGF1R-targeted therapies.

PMID- 29339474
TI  - Robust prediction of individual creative ability from brain functional
      connectivity.
AB  - People's ability to think creatively is a primary means of technological and
      cultural progress, yet the neural architecture of the highly creative brain
      remains largely undefined. Here, we employed a recently developed method in
      functional brain imaging analysis-connectome-based predictive modeling-to
      identify a brain network associated with high-creative ability, using functional
      magnetic resonance imaging (fMRI) data acquired from 163 participants engaged in
      a classic divergent thinking task. At the behavioral level, we found a strong
      correlation between creative thinking ability and self-reported creative behavior
      and accomplishment in the arts and sciences (r = 0.54). At the neural level, we
      found a pattern of functional brain connectivity related to high-creative
      thinking ability consisting of frontal and parietal regions within default,
      salience, and executive brain systems. In a leave-one-out cross-validation
      analysis, we show that this neural model can reliably predict the creative
      quality of ideas generated by novel participants within the sample. Furthermore,
      in a series of external validation analyses using data from two independent task
      fMRI samples and a large task-free resting-state fMRI sample, we demonstrate
      robust prediction of individual creative thinking ability from the same pattern
      of brain connectivity. The findings thus reveal a whole-brain network associated
      with high-creative ability comprised of cortical hubs within default, salience,
      and executive systems-intrinsic functional networks that tend to work in
      opposition-suggesting that highly creative people are characterized by the
      ability to simultaneously engage these large-scale brain networks.

PMID- 29339475
TI  - Electron mean-free-path filtering in Dirac material for improved thermoelectric
      performance.
AB  - Recent advancements in thermoelectric materials have largely benefited from
      various approaches, including band engineering and defect optimization, among
      which the nanostructuring technique presents a promising way to improve the
      thermoelectric figure of merit (zT) by means of reducing the characteristic
      length of the nanostructure, which relies on the belief that phonons' mean free
      paths (MFPs) are typically much longer than electrons'. Pushing the nanostructure
      sizes down to the length scale dictated by electron MFPs, however, has hitherto
      been overlooked as it inevitably sacrifices electrical conduction. Here we report
      through ab initio simulations that Dirac material can overcome this limitation.
      The monotonically decreasing trend of the electron MFP allows filtering of long
      MFP electrons that are detrimental to the Seebeck coefficient, leading to a
      dramatically enhanced power factor. Using SnTe as a material platform, we uncover
      this MFP filtering effect as arising from its unique nonparabolic Dirac band
      dispersion. Room-temperature zT can be enhanced by nearly a factor of 3 if one
      designs nanostructures with grain sizes of ~10 nm. Our work broadens the scope of
      the nanostructuring approach for improving the thermoelectric performance,
      especially for materials with topologically nontrivial electronic dynamics.

PMID- 29339476
TI  - Coding of episodic memory in the human hippocampus.
AB  - Neurocomputational models have long posited that episodic memories in the human
      hippocampus are represented by sparse, stimulus-specific neural codes. A
      concomitant proposal is that when sparse-distributed neural assemblies become
      active, they suppress the activity of competing neurons (neural sharpening). We
      investigated episodic memory coding in the hippocampus and amygdala by measuring
      single-neuron responses from 20 epilepsy patients (12 female) undergoing
      intracranial monitoring while they completed a continuous recognition memory
      task. In the left hippocampus, the distribution of single-neuron activity
      indicated that only a small fraction of neurons exhibited strong responding to a
      given repeated word and that each repeated word elicited strong responding in a
      different small fraction of neurons. This finding reflects sparse distributed
      coding. The remaining large fraction of neurons exhibited a concurrent reduction
      in firing rates relative to novel words. The observed pattern accords with
      longstanding predictions that have previously received scant support from single
      cell recordings from human hippocampus.

PMID- 29339477
TI  - Ebola virus proteins NP, VP35, and VP24 are essential and sufficient to mediate
      nucleocapsid transport.
AB  - The intracytoplasmic movement of nucleocapsids is a crucial step in the life
      cycle of enveloped viruses. Determination of the viral components necessary for
      viral nucleocapsid transport competency is complicated by the dynamic and complex
      nature of nucleocapsid assembly and the lack of appropriate model systems. Here,
      we established a live-cell imaging system based on the ectopic expression of
      fluorescent Ebola virus (EBOV) fusion proteins, allowing the visualization and
      analysis of the movement of EBOV nucleocapsid-like structures with different
      protein compositions. Only three of the five EBOV nucleocapsid proteins
      nucleoprotein, VP35, and VP24-were necessary and sufficient to form transport
      competent nucleocapsid-like structures. The transport of these structures was
      found to be dependent on actin polymerization and to have dynamics that were
      undistinguishable from those of nucleocapsids in EBOV-infected cells. The
      intracytoplasmic movement of nucleocapsid-like structures was completely
      independent of the viral matrix protein VP40 and the viral surface glycoprotein
      GP. However, VP40 greatly enhanced the efficiency of nucleocapsid recruitment
      into filopodia, the sites of EBOV budding.

PMID- 29339478
TI  - Cooperation, clustering, and assortative mixing in dynamic networks.
AB  - Humans' propensity to cooperate is driven by our embeddedness in social networks.
      A key mechanism through which networks promote cooperation is clustering. Within
      clusters, conditional cooperators are insulated from exploitation by
      noncooperators, allowing them to reap the benefits of cooperation. Dynamic
      networks, where ties can be shed and new ties formed, allow for the endogenous
      emergence of clusters of cooperators. Although past work suggests that either
      reputation processes or network dynamics can increase clustering and cooperation,
      existing work on network dynamics conflates reputations and dynamics. Here we
      report results from a large-scale experiment (total n = 2,675) that embedded
      participants in clustered or random networks that were static or dynamic, with
      varying levels of reputational information. Results show that initial network
      clustering predicts cooperation in static networks, but not in dynamic ones.
      Further, our experiment shows that while reputations are important for partner
      choice, cooperation levels are driven purely by dynamics. Supplemental conditions
      confirmed this lack of a reputation effect. Importantly, we find that when
      participants make individual choices to cooperate or defect with each partner, as
      opposed to a single decision that applies to all partners (as is standard in the
      literature on cooperation in networks), cooperation rates in static networks are
      as high as cooperation rates in dynamic networks. This finding highlights the
      importance of structured relations for sustained cooperation, and shows how
      giving experimental participants more realistic choices has important
      consequences for whether dynamic networks promote higher levels of cooperation
      than static networks.

PMID- 29339480
TI  - Local policy proposals can bridge Latino and (most) white Americans' response to
      immigration.
AB  - In the past 15 years, the adoption of subnational immigration policies in the
      United States, such as those established by individual states, has gone from
      nearly zero to over 300 per year. These include welcoming policies aimed at
      attracting and incorporating immigrants, as well as unwelcoming policies directed
      at denying immigrants access to public resources and services. Using data from a
      2016 random digit-dialing telephone survey with an embedded experiment, we
      examine whether institutional support for policies that are either welcoming or
      hostile toward immigrants differentially shape Latinos' and whites' feelings of
      belonging in their state (Arizona/New Mexico, adjacent states with contrasting
      immigration policies). We randomly assigned individuals from the representative
      sample (n = 1,903) of Latinos (US and foreign born) and whites (all US born) to
      consider policies that were either welcoming of or hostile toward immigrants.
      Across both states of residence, Latinos, especially those foreign born,
      regardless of citizenship, expressed more positive affect and greater belonging
      when primed with a welcoming (vs. hostile) policy. Demonstrating the importance
      of local norms, these patterns held among US-born whites, except among self
      identified politically conservative whites, who showed more negative affect and
      lower levels of belonging in response to welcoming policies. Thus, welcoming
      immigration policies, supported by institutional authorities, can create a sense
      of belonging not only among newcomers that is vital to successful integration but
      also among a large segment of the population that is not a direct beneficiary of
      such policies-US-born whites.

PMID- 29339479
TI  - HIF signaling in osteoblast-lineage cells promotes systemic breast cancer growth
      and metastasis in mice.
AB  - Bone metastasis involves dynamic interplay between tumor cells and the local
      stromal environment. In bones, local hypoxia and activation of the hypoxia
      inducible factor (HIF)-1alpha in osteoblasts are essential to maintain skeletal
      homeostasis. However, the role of osteoblast-specific HIF signaling in cancer
      metastasis is unknown. Here, we show that osteoprogenitor cells (OPCs) are
      located in hypoxic niches in the bone marrow and that activation of HIF signaling
      in these cells increases bone mass and favors breast cancer metastasis to bone
      locally. Remarkably, HIF signaling in osteoblast-lineage cells also promotes
      breast cancer growth and dissemination remotely, in the lungs and in other
      tissues distant from bones. Mechanistically, we found that activation of HIF
      signaling in OPCs increases blood levels of the chemokine C-X-C motif ligand 12
      (CXCL12), which leads to a systemic increase of breast cancer cell proliferation
      and dissemination through direct activation of the CXCR4 receptor. Hence, our
      data reveal a previously unrecognized role of the hypoxic osteogenic niche in
      promoting tumorigenesis beyond the local bone microenvironment. They also support
      the concept that the skeleton is an important regulator of the systemic tumor
      environment.

PMID- 29339481
TI  - Repetitive aggressive encounters generate a long-lasting internal state in
      Drosophila melanogaster males.
AB  - Multiple studies have investigated the mechanisms of aggressive behavior in
      Drosophila; however, little is known about the effects of chronic fighting
      experience. Here, we investigated if repeated fighting encounters would induce an
      internal state that could affect the expression of subsequent behavior. We
      trained wild-type males to become winners or losers by repeatedly pairing them
      with hypoaggressive or hyperaggressive opponents, respectively. As described
      previously, we observed that chronic losers tend to lose subsequent fights, while
      chronic winners tend to win them. Olfactory conditioning experiments showed that
      winning is perceived as rewarding, while losing is perceived as aversive.
      Moreover, the effect of chronic fighting experience generalized to other
      behaviors, such as gap-crossing and courtship. We propose that in response to
      repeatedly winning or losing aggressive encounters, male flies form an internal
      state that displays persistence and generalization; fight outcomes can also have
      positive or negative valence. Furthermore, we show that the activities of the
      PPL1-gamma1pedc dopaminergic neuron and the MBON-gamma1pedc>alpha/beta mushroom
      body output neuron are required for aversion to an olfactory cue associated with
      losing fights.

PMID- 29339482
TI  - Global spectral clustering in dynamic networks.
AB  - Community detection is challenging when the network structure is estimated with
      uncertainty. Dynamic networks present additional challenges but also add
      information across time periods. We propose a global community detection method,
      persistent communities by eigenvector smoothing (PisCES), that combines
      information across a series of networks, longitudinally, to strengthen the
      inference for each period. Our method is derived from evolutionary spectral
      clustering and degree correction methods. Data-driven solutions to the problem of
      tuning parameter selection are provided. In simulations we find that PisCES
      performs better than competing methods designed for a low signal-to-noise ratio.
      Recently obtained gene expression data from rhesus monkey brains provide samples
      from finely partitioned brain regions over a broad time span including pre- and
      postnatal periods. Of interest is how gene communities develop over space and
      time; however, once the data are divided into homogeneous spatial and temporal
      periods, sample sizes are very small, making inference quite challenging.
      Applying PisCES to medial prefrontal cortex in monkey rhesus brains from near
      conception to adulthood reveals dense communities that persist, merge, and
      diverge over time and others that are loosely organized and short lived,
      illustrating how dynamic community detection can yield interesting insights into
      processes such as brain development.

PMID- 29339484
TI  - Probabilistic switching circuits in DNA.
AB  - A natural feature of molecular systems is their inherent stochastic behavior. A
      fundamental challenge related to the programming of molecular information
      processing systems is to develop a circuit architecture that controls the
      stochastic states of individual molecular events. Here we present a systematic
      implementation of probabilistic switching circuits, using DNA strand displacement
      reactions. Exploiting the intrinsic stochasticity of molecular interactions, we
      developed a simple, unbiased DNA switch: An input signal strand binds to the
      switch and releases an output signal strand with probability one-half. Using this
      unbiased switch as a molecular building block, we designed DNA circuits that
      convert an input signal to an output signal with any desired probability.
      Further, this probability can be switched between 2 n different values by simply
      varying the presence or absence of n distinct DNA molecules. We demonstrated
      several DNA circuits that have multiple layers and feedback, including a circuit
      that converts an input strand to an output strand with eight different
      probabilities, controlled by the combination of three DNA molecules. These
      circuits combine the advantages of digital and analog computation: They allow a
      small number of distinct input molecules to control a diverse signal range of
      output molecules, while keeping the inputs robust to noise and the outputs at
      precise values. Moreover, arbitrarily complex circuit behaviors can be
      implemented with just a single type of molecular building block.

PMID- 29339483
TI  - HELLS and CDCA7 comprise a bipartite nucleosome remodeling complex defective in
      ICF syndrome.
AB  - Mutations in CDCA7, the SNF2 family protein HELLS (LSH), or the DNA
      methyltransferase DNMT3b cause immunodeficiency-centromeric instability-facial
      anomalies (ICF) syndrome. While it has been speculated that DNA methylation
      defects cause this disease, little is known about the molecular function of CDCA7
      and its functional relationship to HELLS and DNMT3b. Systematic analysis of how
      the cell cycle, H3K9 methylation, and the mitotic kinase Aurora B affect
      proteomic profiles of chromatin in Xenopus egg extracts revealed that HELLS and
      CDCA7 form a stoichiometric complex on chromatin, in a manner sensitive to Aurora
      B. Although HELLS alone fails to remodel nucleosomes, we demonstrate that the
      HELLS-CDCA7 complex possesses nucleosome remodeling activity. Furthermore, CDCA7
      is essential for loading HELLS onto chromatin, and CDCA7 harboring patient ICF
      mutations fails to recruit the complex to chromatin. Together, our study
      identifies a unique bipartite nucleosome remodeling complex where the functional
      remodeling activity is split between two proteins and thus delineates the
      defective pathway in ICF syndrome.

PMID- 29339485
TI  - Elevated d-2-hydroxyglutarate during colitis drives progression to colorectal
      cancer.
AB  - d-2-hydroxyglutarate (D2HG) is produced in the tricarboxylic acid cycle and is
      quickly converted to alpha-ketoglutarate by d-2-hydroxyglutarate dehydrogenase
      (D2HGDH). In a mouse model of colitis-associated colon cancer (CAC), urine level
      of D2HG during colitis correlates positively with subsequent polyp counts and
      severity of dysplasia. The i.p. injection of D2HG results in delayed recovery
      from colitis and severe tumorigenesis. The colonic expression of D2HGDH is
      decreased in ulcerative colitis (UC) patients at baseline who progress to cancer.
      Hypoxia-inducible factor (Hif)-1alpha is a key regulator of D2HGDH transcription.
      Our study identifies urine D2HG and tissue D2HGDH expression as biomarkers to
      identify patients at risk for progressing from colitis to cancer. The D2HG/D2HGDH
      pathway provides potential therapeutic targets for the treatment of CAC.

PMID- 29339487
TI  - Uncovering the role of the East Asian jet stream and heterogeneities in
      atmospheric rivers affecting the western United States.
AB  - Atmospheric rivers (ARs) exert major socioeconomic repercussions along the US
      West Coast by inducing heavy rainfall, flooding, strong winds, and storm surge.
      Despite the significant societal and economic repercussions of these storms, our
      understanding of the physical drivers responsible for their interannual
      variability is limited, with different climate modes identified as possible
      mechanisms. Here we show that the Pacific-Japan (PJ) teleconnections/patterns and
      the East Asian subtropical jet (EASJ) exhibit a strong linkage with the total
      frequency of ARs making landfall over the western United States, much stronger
      than the other potential climate modes previously considered. While our findings
      indicate that the PJ pattern and EASJ are the most relevant climate modes driving
      the overall AR activity, we also uncover heterogeneities in AR tracks.
      Specifically, we show that not all ARs making landfall along the West Coast come
      from a single population, but rather that it is possible to stratify these storms
      into three clusters. While the PJ pattern and EASJ are major drivers of AR
      activity for two clusters, the cluster that primarily affects the US Southwest is
      largely driven by other climate modes [El Nino Southern Oscillation (ENSO), the
      Atlantic meridional mode (AMM), the Pacific-North America (PNA) teleconnection
      pattern, and the North Pacific Gyre Oscillation (NPGO)]. Therefore, important
      regional differences exist and this information can substantially enhance our
      ability to predict and prepare for these storms and their impacts.

PMID- 29339486
TI  - Cell-type-specific role for nucleus accumbens neuroligin-2 in depression and
      stress susceptibility.
AB  - Behavioral coping strategies are critical for active resilience to stress and
      depression; here we describe a role for neuroligin-2 (NLGN-2) in the nucleus
      accumbens (NAc). Neuroligins (NLGN) are a family of neuronal postsynaptic cell
      adhesion proteins that are constituents of the excitatory and inhibitory synapse.
      Importantly, NLGN-3 and NLGN-4 mutations are strongly implicated as candidates
      underlying the development of neuropsychiatric disorders with social disturbances
      such as autism, but the role of NLGN-2 in neuropsychiatric disease states is
      unclear. Here we show a reduction in NLGN-2 gene expression in the NAc of
      patients with major depressive disorder. Chronic social defeat stress in mice
      also decreases NLGN-2 selectively in dopamine D1-positive cells, but not dopamine
      D2-positive cells, within the NAc of stress-susceptible mice. Functional NLGN-2
      knockdown produces bidirectional, cell-type-specific effects: knockdown in
      dopamine D1-positive cells promotes subordination and stress susceptibility,
      whereas knockdown in dopamine D2-positive cells mediates active defensive
      behavior. These findings establish a behavioral role for NAc NLGN-2 in stress and
      depression; provide a basis for targeted, cell-type specific therapy; and
      highlight the role of active behavioral coping mechanisms in stress
      susceptibility.

PMID- 29339489
TI  - Rogue waves and large deviations in deep sea.
AB  - The appearance of rogue waves in deep sea is investigated by using the modified
      nonlinear Schrodinger (MNLS) equation in one spatial dimension with random
      initial conditions that are assumed to be normally distributed, with a spectrum
      approximating realistic conditions of a unidirectional sea state. It is shown
      that one can use the incomplete information contained in this spectrum as prior
      and supplement this information with the MNLS dynamics to reliably estimate the
      probability distribution of the sea surface elevation far in the tail at later
      times. Our results indicate that rogue waves occur when the system hits unlikely
      pockets of wave configurations that trigger large disturbances of the surface
      height. The rogue wave precursors in these pockets are wave patterns of regular
      height, but with a very specific shape that is identified explicitly, thereby
      allowing for early detection. The method proposed here combines Monte Carlo
      sampling with tools from large deviations theory that reduce the calculation of
      the most likely rogue wave precursors to an optimization problem that can be
      solved efficiently. This approach is transferable to other problems in which the
      system's governing equations contain random initial conditions and/or parameters.

PMID- 29339488
TI  - Ultrafast imaging of cell elasticity with optical microelastography.
AB  - Elasticity is a fundamental cellular property that is related to the anatomy,
      functionality, and pathological state of cells and tissues. However, current
      techniques based on cell deformation, atomic force microscopy, or Brillouin
      scattering are rather slow and do not always accurately represent cell
      elasticity. Here, we have developed an alternative technique by applying shear
      wave elastography to the micrometer scale. Elastic waves were mechanically
      induced in live mammalian oocytes using a vibrating micropipette. These audible
      frequency waves were observed optically at 200,000 frames per second and tracked
      with an optical flow algorithm. Whole-cell elasticity was then mapped using an
      elastography method inspired by the seismology field. Using this approach we show
      that the elasticity of mouse oocytes is decreased when the oocyte cytoskeleton is
      disrupted with cytochalasin B. The technique is fast (less than 1 ms for data
      acquisition), precise (spatial resolution of a few micrometers), able to map
      internal cell structures, and robust and thus represents a tractable option for
      interrogating biomechanical properties of diverse cell types.

PMID- 29339490
TI  - Structural basis of sterol recognition and nonvesicular transport by lipid
      transfer proteins anchored at membrane contact sites.
AB  - Membrane contact sites (MCSs) in eukaryotic cells are hotspots for lipid
      exchange, which is essential for many biological functions, including regulation
      of membrane properties and protein trafficking. Lipid transfer proteins anchored
      at membrane contact sites (LAMs) contain sterol-specific lipid transfer domains
      [StARkin domain (SD)] and multiple targeting modules to specific membrane
      organelles. Elucidating the structural mechanisms of targeting and ligand
      recognition by LAMs is important for understanding the interorganelle
      communication and exchange at MCSs. Here, we determined the crystal structures of
      the yeast Lam6 pleckstrin homology (PH)-like domain and the SDs of Lam2 and Lam4
      in the apo form and in complex with ergosterol. The Lam6 PH-like domain displays
      a unique PH domain fold with a conserved N-terminal alpha-helix. The Lam6 PH-like
      domain lacks the basic surface for phosphoinositide binding, but contains
      hydrophobic patches on its surface, which are critical for targeting to
      endoplasmic reticulum (ER)-mitochondrial contacts. Structures of the LAM SDs
      display a helix-grip fold with a hydrophobic cavity and a flexible Omega1-loop as
      a lid. Ergosterol is bound to the pocket in a head-down orientation, with its
      hydrophobic acyl group located in the tunnel entrance. The Omega1-loop in an open
      conformation is essential for ergosterol binding by direct hydrophobic
      interaction. Structural comparison suggested that the sterol binding mode of the
      Lam2 SD2 is likely conserved among the sterol transfer proteins of the StARkin
      superfamily. Structural models of full-length Lam2 correlated with the sterol
      transport function at the membrane contact sites.

PMID- 29339491
TI  - Kinase-independent function of E-type cyclins in liver cancer.
AB  - E-type cyclins (cyclins E1 and E2) are components of the core cell cycle
      machinery and are overexpressed in many human tumor types. E cyclins are thought
      to drive tumor cell proliferation by activating the cyclin-dependent kinase 2
      (CDK2). The cyclin E1 gene represents the site of recurrent integration of the
      hepatitis B virus in the pathogenesis of hepatocellular carcinoma, and this event
      is associated with strong up-regulation of cyclin E1 expression. Regardless of
      the underlying mechanism of tumorigenesis, the majority of liver cancers
      overexpress E-type cyclins. Here we used conditional cyclin E knockout mice and a
      liver cancer model to test the requirement for the function of E cyclins in liver
      tumorigenesis. We show that a ubiquitous, global shutdown of E cyclins did not
      visibly affect postnatal development or physiology of adult mice. However, an
      acute ablation of E cyclins halted liver cancer progression. We demonstrated that
      also human liver cancer cells critically depend on E cyclins for proliferation.
      In contrast, we found that the function of the cyclin E catalytic partner, CDK2,
      is dispensable in liver cancer cells. We observed that E cyclins drive
      proliferation of tumor cells in a CDK2- and kinase-independent mechanism. Our
      study suggests that compounds which degrade or inhibit cyclin E might represent a
      highly selective therapeutic strategy for patients with liver cancer, as these
      compounds would selectively cripple proliferation of tumor cells, while sparing
      normal tissues.

PMID- 29339492
TI  - Cytocapsular tubes conduct cell translocation.
AB  - Cell locomotion is essential for multicellular organism embryo development, organ
      homeostasis, tissue regeneration, immune responses, and tumor metastasis. Here we
      report that single mammalian cells can generate two extracellular membranous
      compartments: cytocapsulae and cytocapsular tubes. Cells migrate in cytocapsulae
      and engender cytocapsular tubes, which exhibit pleiotropic biological functions
      and provide tubular routes for directed cell transportation. Ultrastructural
      analysis by electron microscope revealed that nanoprotrusions surround and anchor
      cytocapsular tubes in place. Multiple cytocapsular tubes interconnect and form
      networks supporting directed cell transportation in diverse directions. Enhanced
      translation initiation factor eIF4E up-regulates translation of transcripts
      encoding proteins important for organelle development. Thus, this study proposes
      a mechanism of directed cell translocation in cytocapsular tubes, which may
      facilitate the management of diseases, including tumor metastasis.

PMID- 29339493
TI  - Emergent chirality in the electric polarization texture of titanate
      superlattices.
AB  - Chirality is a geometrical property by which an object is not superimposable onto
      its mirror image, thereby imparting a handedness. Chirality determines many
      important properties in nature-from the strength of the weak interactions
      according to the electroweak theory in particle physics to the binding of enzymes
      with naturally occurring amino acids or sugars, reactions that are fundamental
      for life. In condensed matter physics, the prediction of topologically protected
      magnetic skyrmions and related spin textures in chiral magnets has stimulated
      significant research. If the magnetic dipoles were replaced by their electrical
      counterparts, then electrically controllable chiral devices could be designed.
      Complex oxide BaTiO3/SrTiO3 nanocomposites and PbTiO3/SrTiO3 superlattices are
      perfect candidates, since "polar vortices," in which a continuous rotation of
      ferroelectric polarization spontaneously forms, have been recently discovered.
      Using resonant soft X-ray diffraction, we report the observation of a strong
      circular dichroism from the interaction between circularly polarized light and
      the chiral electric polarization texture that emerges in PbTiO3/SrTiO3
      superlattices. This hallmark of chirality is explained by a helical rotation of
      electric polarization that second-principles simulations predict to reside within
      complex 3D polarization textures comprising ordered topological line defects. The
      handedness of the texture can be topologically characterized by the sign of the
      helicity number of the chiral line defects. This coupling between the optical and
      novel polar properties could be exploited to encode chiral signatures into photon
      or electron beams for information processing.

PMID- 29339494
TI  - Strongly enhanced bacterial bioluminescence with the ilux operon for single-cell
      imaging.
AB  - Bioluminescence imaging of single cells is often complicated by the requirement
      of exogenous luciferins that can be poorly cell-permeable or produce high
      background signal. Bacterial bioluminescence is unique in that it uses reduced
      flavin mononucleotide as a luciferin, which is abundant in all cells, making this
      system purely genetically encodable by the lux operon. Unfortunately, the use of
      bacterial bioluminescence has been limited by its low brightness compared with
      other luciferases. Here, we report the generation of an improved lux operon named
      ilux with an approximately sevenfold increased brightness when expressed in
      Escherichia coli; ilux can be used to image single E. coli cells with enhanced
      spatiotemporal resolution over several days. In addition, since only
      metabolically active cells produce bioluminescent signal, we show that ilux can
      be used to observe the effect of different antibiotics on cell viability on the
      single-cell level.

PMID- 29339495
TI  - Streamlined circular proximity ligation assay provides high stringency and
      compatibility with low-affinity antibodies.
AB  - Proximity ligation assay (PLA) is a powerful tool for quantitative detection of
      protein biomarkers in biological fluids and tissues. Here, we present the
      circular proximity ligation assay (c-PLA), a highly specific protein detection
      method that outperforms traditional PLA in stringency, ease of use, and
      compatibility with low-affinity reagents. In c-PLA, two proximity probes bind to
      an analyte, providing a scaffolding that positions two free oligonucleotides such
      that they can be ligated into a circular DNA molecule. This assay format
      stabilizes antigen proximity probe complexes and enhances stringency by reducing
      the probability of random background ligation events. Circle formation also
      increases selectivity, since the uncircularized DNA can be removed enzymatically.
      We compare this method with traditional PLA on several biomarkers and show that
      the higher stringency for c-PLA improves reproducibility and enhances sensitivity
      in both buffer and human plasma. The limit of detection ranges from femtomolar to
      nanomolar concentrations for both methods. Kinetic analyses using surface plasmon
      resonance (SPR) and biolayer interferometry (BLI) reveal that the variation in
      limit of detection is due to the variation in antibody affinity and that c-PLA
      outperforms traditional PLA for low-affinity antibodies. The lower background
      signal can be used to increase proximity probe concentration while maintaining a
      high signal-to-noise ratio, thereby enabling the use of low-affinity reagents in
      a homogeneous assay format. We anticipate that the advantages of c-PLA will be
      useful in a variety of clinical protein detection applications where high
      affinity reagents are lacking.

PMID- 29339496
TI  - Thymic stromal lymphopoietin drives the development of IL-13+ Th2 cells.
AB  - T helper 2 (Th2) cells are pivotal in the development of allergy. Allergen
      exposure primes IL-4+ Th2 cells in lymph node, but production of effector
      cytokines including IL-5 and IL-13 is thought to require additional signals from
      antigen and the environment. Here we report that a substantial proportion of
      naive CD4+ T cells in spleen and lymph node express receptors for the epithelium
      derived inflammatory cytokine thymic stromal lymphopoietin (TSLP). Culture of
      naive CD4+ T cells in anti-(a)CD3, aCD28, and TSLP-supplemented Th2 conditions
      enabled the development of a unique population of IL-13-single positive (IL-13
      SP) CD4+ T cells; TSLP and Th2 conditions were both required for their
      development. Sorting experiments revealed that IL-13-SP Th2 cells originated from
      IL-4-negative precursors and coexpressed transcripts for the Th2 cytokines IL-5
      and IL-9. In vivo, high TSLP levels acted directly on CD4+ T cells to induce the
      development of IL-13-SP and IL-4+IL-13+ double-positive populations in lymph
      node. These cells were phenotypically similar to Th2 effector cells and were
      CXCR5lowPD1low and expressed low levels of Bcl6 and Il21 transcripts and high
      levels of Gata3, Il3, and Il5 Our findings suggest a role of TSLP in directly
      promoting Th2 cell effector function and support the notion of TSLP as a key
      driver of Th2 inflammation.

PMID- 29339497
TI  - Ocean convergence and the dispersion of flotsam.
AB  - Floating oil, plastics, and marine organisms are continually redistributed by
      ocean surface currents. Prediction of their resulting distribution on the surface
      is a fundamental, long-standing, and practically important problem. The dominant
      paradigm is dispersion within the dynamical context of a nondivergent flow:
      objects initially close together will on average spread apart but the area of
      surface patches of material does not change. Although this paradigm is likely
      valid at mesoscales, larger than 100 km in horizontal scale, recent theoretical
      studies of submesoscales (less than ~10 km) predict strong surface convergences
      and downwelling associated with horizontal density fronts and cyclonic vortices.
      Here we show that such structures can dramatically concentrate floating material.
      More than half of an array of ~200 surface drifters covering ~20 * 20 km2
      converged into a 60 * 60 m region within a week, a factor of more than 105
      decrease in area, before slowly dispersing. As predicted, the convergence
      occurred at density fronts and with cyclonic vorticity. A zipperlike structure
      may play an important role. Cyclonic vorticity and vertical velocity reached
      0.001 s-1 and 0.01 ms-1, respectively, which is much larger than usually
      inferred. This suggests a paradigm in which nearby objects form submesoscale
      clusters, and these clusters then spread apart. Together, these effects set both
      the overall extent and the finescale texture of a patch of floating material.
      Material concentrated at submesoscale convergences can create unique communities
      of organisms, amplify impacts of toxic material, and create opportunities to more
      efficiently recover such material.

PMID- 29339499
TI  - Supercritical CO2 uptake by nonswelling phyllosilicates.
AB  - Interactions between supercritical (sc) CO2 and minerals are important when CO2
      is injected into geologic formations for storage and as working fluids for
      enhanced oil recovery, hydraulic fracturing, and geothermal energy extraction. It
      has previously been shown that at the elevated pressures and temperatures of the
      deep subsurface, scCO2 alters smectites (typical swelling phyllosilicates).
      However, less is known about the effects of scCO2 on nonswelling phyllosilicates
      (illite and muscovite), despite the fact that the latter are the dominant clay
      minerals in deep subsurface shales and mudstones. Our studies conducted by using
      single crystals, combining reaction (incubation with scCO2), visualization
      [atomic force microscopy (AFM)], and quantifications (AFM, X-ray photoelectron
      spectroscopy, X-ray diffraction, and off-gassing measurements) revealed
      unexpectedly high CO2 uptake that far exceeded its macroscopic surface area.
      Results from different methods collectively suggest that CO2 partially entered
      the muscovite interlayers, although the pathways remain to be determined. We
      hypothesize that preferential dissolution at weaker surface defects and frayed
      edges allows CO2 to enter the interlayers under elevated pressure and
      temperature, rather than by diffusing solely from edges deeply into interlayers.
      This unexpected uptake of CO2, can increase CO2 storage capacity by up to ~30%
      relative to the capacity associated with residual trapping in a 0.2-porosity
      sandstone reservoir containing up to 18 mass % of illite/muscovite. This excess
      CO2 uptake constitutes a previously unrecognized potential trapping mechanism.

PMID- 29339498
TI  - MAFA missense mutation causes familial insulinomatosis and diabetes mellitus.
AB  - The beta-cell-enriched MAFA transcription factor plays a central role in
      regulating glucose-stimulated insulin secretion while also demonstrating
      oncogenic transformation potential in vitro. No disease-causing MAFA variants
      have been previously described. We investigated a large pedigree with autosomal
      dominant inheritance of diabetes mellitus or insulinomatosis, an adult-onset
      condition of recurrent hyperinsulinemic hypoglycemia caused by multiple insulin
      secreting neuroendocrine tumors of the pancreas. Using exome sequencing, we
      identified a missense MAFA mutation (p.Ser64Phe, c.191C>T) segregating with both
      phenotypes of insulinomatosis and diabetes. This mutation was also found in a
      second unrelated family with the same clinical phenotype, while no germline or
      somatic MAFA mutations were identified in nine patients with sporadic
      insulinomatosis. In the two families, insulinomatosis presented more frequently
      in females (eight females/two males) and diabetes more often in males (12
      males/four females). Four patients from the index family, including two
      homozygotes, had a history of congenital cataract and/or glaucoma. The p.Ser64Phe
      mutation was found to impair phosphorylation within the transactivation domain of
      MAFA and profoundly increased MAFA protein stability under both high and low
      glucose concentrations in beta-cell lines. In addition, the transactivation
      potential of p.Ser64Phe MAFA in beta-cell lines was enhanced compared with wild
      type MAFA. In summary, the p.Ser64Phe missense MAFA mutation leads to familial
      insulinomatosis or diabetes by impacting MAFA protein stability and
      transactivation ability. The human phenotypes associated with the p.Ser64Phe MAFA
      missense mutation reflect both the oncogenic capacity of MAFA and its key role in
      islet beta-cell activity.

PMID- 29339501
TI  - Correction to Supporting Information for Carlson et al., Effect of oil palm
      sustainability certification on deforestation and fire in Indonesia.

PMID- 29339500
TI  - Regulation of the stability of RGF1 receptor by the ubiquitin-specific proteases
      UBP12/UBP13 is critical for root meristem maintenance.
AB  - ROOT MERISTEM GROWTH FACTOR (RGF) 1 is an important peptide hormone that
      regulates root growth. Upon binding to its receptor, RGFR1, RGF1 regulates the
      expression of two transcription factors, PLETHORA 1 and 2 (PLT1/2), to influence
      root meristem development. Here, we show that the ubiquitin-specific proteases
      UBP12 and UBP13 are positive regulators of root meristem development and that
      UBP13 interacts directly with RGF1 receptor (RGFR1) and its close homolog RGFR2.
      The ubp12,13 double-mutant root is completely insensitive to exogenous applied
      RGF1. Consistent with this result, RGF1-induced ubiquitination and turnover of
      RGFR1 protein were accelerated in ubp12,13-mutant plants but were delayed in
      transgenic plants overexpressing UBP13 Genetic analysis showed that PLT2 or RGFR1
      overexpression partially rescued the short-root phenotype and the reduced
      cortical root meristem cell number in ubp12,13 plants. Together, our results
      demonstrate that UBP12/13 are regulators of the RGF1-RGFR1-PLT1/2 signaling
      pathway and that UBP12/13 can counteract RGF1-induced RGFR1 ubiquitination,
      stabilize RGFR1, and maintain root cell sensitivity to RGF1.

PMID- 29339502
TI  - Protein aggregation of the p63 transcription factor underlies severe skin
      fragility in AEC syndrome.
AB  - The p63 gene encodes a master regulator of epidermal commitment, development, and
      differentiation. Heterozygous mutations in the C-terminal domain of the p63 gene
      can cause ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome, a
      life-threatening disorder characterized by skin fragility and severe, long
      lasting skin erosions. Despite deep knowledge of p63 functions, little is known
      about mechanisms underlying disease pathology and possible treatments. Here, we
      show that multiple AEC-associated p63 mutations, but not those causative of other
      diseases, lead to thermodynamic protein destabilization, misfolding, and
      aggregation, similar to the known p53 gain-of-function mutants found in cancer.
      AEC mutant proteins exhibit impaired DNA binding and transcriptional activity,
      leading to dominant negative effects due to coaggregation with wild-type p63 and
      p73. Importantly, p63 aggregation occurs also in a conditional knock-in mouse
      model for the disorder, in which the misfolded p63 mutant protein leads to severe
      epidermal defects. Variants of p63 that abolish aggregation of the mutant
      proteins are able to rescue p63's transcriptional function in reporter assays as
      well as in a human fibroblast-to-keratinocyte conversion assay. Our studies
      reveal that AEC syndrome is a protein aggregation disorder and opens avenues for
      therapeutic intervention.

PMID- 29339503
TI  - Heteromeric interactions regulate butyrophilin (BTN) and BTN-like molecules
      governing gammadelta T cell biology.
AB  - The long-held view that gamma delta (gammadelta) T cells in mice and humans are
      fundamentally dissimilar, as are gammadelta cells in blood and peripheral
      tissues, has been challenged by emerging evidence of the cells' regulation by
      butyrophilin (BTN) and butyrophilin-like (BTNL) molecules. Thus, murine Btnl1 and
      the related gene, Skint1, mediate T cell receptor (TCR)-dependent selection of
      murine intraepithelial gammadelta T cell repertoires in gut and skin,
      respectively; BTNL3 and BTNL8 are TCR-dependent regulators of human gut
      gammadelta cells; and BTN3A1 is essential for TCR-dependent activation of human
      peripheral blood Vgamma9Vdelta2+ T cells. However, some observations concerning
      BTN/Btnl molecules continue to question the extent of mechanistic conservation.
      In particular, murine and human gut gammadelta cell regulation depends on
      pairings of Btnl1 and Btnl6 and BTNL3 and BTNL8, respectively, whereas blood
      gammadelta cells are reported to be regulated by BTN3A1 independent of other
      BTNs. Addressing this paradox, we show that BTN3A2 regulates the subcellular
      localization of BTN3A1, including functionally important associations with the
      endoplasmic reticulum (ER), and is specifically required for optimal BTN3A1
      mediated activation of Vgamma9Vdelta2+ T cells. Evidence that BTNL3/BTNL8 and
      Btnl1/Btnl6 likewise associate with the ER reinforces the prospect of broadly
      conserved mechanisms underpinning the selection and activation of gammadelta
      cells in mice and humans, and in blood and extralymphoid sites.

PMID- 29339504
TI  - Complement pathway gene activation and rising circulating immune complexes
      characterize early disease in HIV-associated tuberculosis.
AB  - The transition between latent and active tuberculosis (TB) occurs before symptom
      onset. Better understanding of the early events in subclinical disease will
      facilitate the development of diagnostics and interventions that improve TB
      control. This is particularly relevant in the context of HIV-1 coinfection where
      progression of TB is more likely. In a recent study using [18F]-fluoro-2-deoxy-d
      glucose positron emission/computed tomography (FDG-PET/CT) on 35 asymptomatic,
      HIV-1-infected adults, we identified 10 participants with radiographic evidence
      of subclinical disease, significantly more likely to progress than the 25
      participants without. To gain insight into the biological events in early
      disease, we performed blood-based whole genome transcriptomic analysis on these
      participants and 15 active patients with TB. We found transcripts representing
      the classical complement pathway and Fcgamma receptor 1 overabundant from
      subclinical stages of disease. Levels of circulating immune (antibody/antigen)
      complexes also increased in subclinical disease and were highly correlated with
      C1q transcript abundance. To validate our findings, we analyzed transcriptomic
      data from a publicly available dataset where samples were available in the 2 y
      before TB disease presentation. Transcripts representing the classical complement
      pathway and Fcgamma receptor 1 were also differentially expressed in the 12 mo
      before disease presentation. Our results indicate that levels of antibody/antigen
      complexes increase early in disease, associated with increased gene expression of
      C1q and Fcgamma receptors that bind them. Understanding the role this plays in
      disease progression may facilitate development of interventions that prevent
      this, leading to a more favorable outcome and may also be important to diagnostic
      development.

PMID- 29339505
TI  - Nonenzymatic release of N7-methylguanine channels repair of abasic sites into an
      AP endonuclease-independent pathway in Arabidopsis.
AB  - Abasic (apurinic/apyrimidinic, AP) sites in DNA arise from spontaneous base loss
      or by enzymatic removal during base excision repair. It is commonly accepted that
      both classes of AP site have analogous biochemical properties and are equivalent
      substrates for AP endonucleases and AP lyases, although the relative roles of
      these two types of enzymes are not well understood. We provide here genetic and
      biochemical evidence that, in Arabidopsis, AP sites generated by spontaneous loss
      of N7-methylguanine (N7-meG) are exclusively repaired through an AP endonuclease
      independent pathway initiated by FPG, a bifunctional DNA glycosylase with AP
      lyase activity. Abasic site incision catalyzed by FPG generates a single
      nucleotide gap with a 3'-phosphate terminus that is processed by the DNA 3'
      phosphatase ZDP before repair is completed. We further show that the major AP
      endonuclease in Arabidopsis (ARP) incises AP sites generated by enzymatic N7-meG
      excision but, unexpectedly, not those resulting from spontaneous N7-meG loss.
      These findings, which reveal previously undetected differences between products
      of enzymatic and nonenzymatic base release, may shed light on the evolution and
      biological roles of AP endonucleases and AP lyases.

PMID- 29339506
TI  - Development and retention of a primordial moonlighting pathway of protein
      modification in the absence of selection presents a puzzle.
AB  - Lipoic acid is synthesized by a remarkably atypical pathway in which the cofactor
      is assembled on its cognate proteins. An octanoyl moiety diverted from fatty acid
      synthesis is covalently attached to the acceptor protein, and sulfur insertion at
      carbons 6 and 8 of the octanoyl moiety form the lipoyl cofactor. Covalent
      attachment of this cofactor is required for function of several central
      metabolism enzymes, including the glycine cleavage H protein (GcvH). In Bacillus
      subtilis, GcvH is the sole substrate for lipoate assembly. Hence lipoic acid
      requiring 2-oxoacid dehydrogenase (OADH) proteins acquire the cofactor only by
      transfer from lipoylated GcvH. Lipoyl transfer has been argued to be the
      primordial pathway of OADH lipoylation. The Escherichia coli pathway where
      lipoate is directly assembled on both its GcvH and OADH proteins, is proposed to
      have arisen later. Because roughly 3 billion years separate the divergence of
      these bacteria, it is surprising that E. coli GcvH functionally substitutes for
      the B. subtilis protein in lipoyl transfer. Known and putative GcvHs from other
      bacteria and eukaryotes also substitute for B. subtilis GcvH in OADH
      modification. Because glycine cleavage is the primary GcvH role in ancestral
      bacteria that lack OADH enzymes, lipoyl transfer is a "moonlighting" function:
      that is, development of a new function while retaining the original function.
      This moonlighting has been conserved in the absence of selection by some, but not
      all, GcvH proteins. Moreover, Aquifex aeolicus encodes five putative GcvHs, two
      of which have the moonlighting function, whereas others function only in glycine
      cleavage.

PMID- 29339508
TI  - Human ectoparasites and the spread of plague in Europe during the Second
      Pandemic.
AB  - Plague, caused by the bacterium Yersinia pestis, can spread through human
      populations by multiple transmission pathways. Today, most human plague cases are
      bubonic, caused by spillover of infected fleas from rodent epizootics, or
      pneumonic, caused by inhalation of infectious droplets. However, little is known
      about the historical spread of plague in Europe during the Second Pandemic (14
      19th centuries), including the Black Death, which led to high mortality and
      recurrent epidemics for hundreds of years. Several studies have suggested that
      human ectoparasite vectors, such as human fleas (Pulex irritans) or body lice
      (Pediculus humanus humanus), caused the rapidly spreading epidemics. Here, we
      describe a compartmental model for plague transmission by a human ectoparasite
      vector. Using Bayesian inference, we found that this model fits mortality curves
      from nine outbreaks in Europe better than models for pneumonic or rodent
      transmission. Our results support that human ectoparasites were primary vectors
      for plague during the Second Pandemic, including the Black Death (1346-1353),
      ultimately challenging the assumption that plague in Europe was predominantly
      spread by rats.

PMID- 29339507
TI  - Large-scale comparative epigenomics reveals hierarchical regulation of non-CG
      methylation in Arabidopsis.
AB  - Genome-wide characterization by next-generation sequencing has greatly improved
      our understanding of the landscape of epigenetic modifications. Since 2008, whole
      genome bisulfite sequencing (WGBS) has become the gold standard for DNA
      methylation analysis, and a tremendous amount of WGBS data has been generated by
      the research community. However, the systematic comparison of DNA methylation
      profiles to identify regulatory mechanisms has yet to be fully explored. Here we
      reprocessed the raw data of over 500 publicly available Arabidopsis WGBS
      libraries from various mutant backgrounds, tissue types, and stress treatments
      and also filtered them based on sequencing depth and efficiency of bisulfite
      conversion. This enabled us to identify high-confidence differentially methylated
      regions (hcDMRs) by comparing each test library to over 50 high-quality wild-type
      controls. We developed statistical and quantitative measurements to analyze the
      overlapping of DMRs and to cluster libraries based on their effect on DNA
      methylation. In addition to confirming existing relationships, we revealed
      unanticipated connections between well-known genes. For instance, MET1 and CMT3
      were found to be required for the maintenance of asymmetric CHH methylation at
      nonoverlapping regions of CMT2 targeted heterochromatin. Our comparative
      methylome approach has established a framework for extracting biological insights
      via large-scale comparison of methylomes and can also be adopted for other
      genomics datasets.

PMID- 29339509
TI  - Biodegradable Piezoelectric Force Sensor.
AB  - Measuring vital physiological pressures is important for monitoring health
      status, preventing the buildup of dangerous internal forces in impaired organs,
      and enabling novel approaches of using mechanical stimulation for tissue
      regeneration. Pressure sensors are often required to be implanted and directly
      integrated with native soft biological systems. Therefore, the devices should be
      flexible and at the same time biodegradable to avoid invasive removal surgery
      that can damage directly interfaced tissues. Despite recent achievements in
      degradable electronic devices, there is still a tremendous need to develop a
      force sensor which only relies on safe medical materials and requires no complex
      fabrication process to provide accurate information on important biophysiological
      forces. Here, we present a strategy for material processing, electromechanical
      analysis, device fabrication, and assessment of a piezoelectric Poly-l-lactide
      (PLLA) polymer to create a biodegradable, biocompatible piezoelectric force
      sensor, which only employs medical materials used commonly in Food and Drug
      Administration-approved implants, for the monitoring of biological forces. We
      show the sensor can precisely measure pressures in a wide range of 0-18 kPa and
      sustain a reliable performance for a period of 4 d in an aqueous environment. We
      also demonstrate this PLLA piezoelectric sensor can be implanted inside the
      abdominal cavity of a mouse to monitor the pressure of diaphragmatic contraction.
      This piezoelectric sensor offers an appealing alternative to present
      biodegradable electronic devices for the monitoring of intraorgan pressures. The
      sensor can be integrated with tissues and organs, forming self-sensing bionic
      systems to enable many exciting applications in regenerative medicine, drug
      delivery, and medical devices.

PMID- 29339510
TI  - Artificial intelligence exploration of unstable protocells leads to predictable
      properties and discovery of collective behavior.
AB  - Protocell models are used to investigate how cells might have first assembled on
      Earth. Some, like oil-in-water droplets, can be seemingly simple models, while
      able to exhibit complex and unpredictable behaviors. How such simple oil-in-water
      systems can come together to yield complex and life-like behaviors remains a key
      question. Herein, we illustrate how the combination of automated experimentation
      and image processing, physicochemical analysis, and machine learning allows
      significant advances to be made in understanding the driving forces behind oil-in
      water droplet behaviors. Utilizing >7,000 experiments collected using an
      autonomous robotic platform, we illustrate how smart automation cannot only help
      with exploration, optimization, and discovery of new behaviors, but can also be
      core to developing fundamental understanding of such systems. Using this process,
      we were able to relate droplet formulation to behavior via predicted physical
      properties, and to identify and predict more occurrences of a rare collective
      droplet behavior, droplet swarming. Proton NMR spectroscopic and qualitative pH
      methods enabled us to better understand oil dissolution, chemical change, phase
      transitions, and droplet and aqueous phase flows, illustrating the utility of the
      combination of smart-automation and traditional analytical chemistry techniques.
      We further extended our study for the simultaneous exploration of both the oil
      and aqueous phases using a robotic platform. Overall, this work shows that the
      combination of chemistry, robotics, and artificial intelligence enables
      discovery, prediction, and mechanistic understanding in ways that no one approach
      could achieve alone.

PMID- 29339511
TI  - The role of obesity in exceptionally slow US mortality improvement.
AB  - Recent studies have described a reduction in the rate of improvement in American
      mortality. The pace of improvement is also slow by international standards. This
      paper attempts to identify the extent to which rising body mass index (BMI) is
      responsible for reductions in the rate of mortality improvement in the United
      States. The data for this study were obtained from subsequent cohorts of the
      National Health and Nutrition Examination Survey (NHANES III, 1988-1994; NHANES
      continuous, 1999-2010) and from the NHANES linked mortality files, which include
      follow-up into death records through December 2011. The role of BMI was estimated
      using Cox models comparing mortality trends in the presence and absence of
      adjustment for maximum lifetime BMI (Max BMI). Introducing Max BMI into a Cox
      model controlling for age and sex raised the annual rate of mortality decline by
      0.54% (95% confidence interval 0.45-0.64%). Results were robust to the inclusion
      of other variables in the model, to differences in how Max BMI was measured, and
      to how trends were evaluated. The effect of rising Max BMI is large relative to
      international mortality trends and to alternative mortality futures simulated by
      the Social Security Administration. The increase in Max BMI over the period 1988
      2011 is estimated to have reduced life expectancy at age 40 by 0.9 years in 2011
      (95% confidence interval 0.7-1.1 years) and accounted for 186,000 excess deaths
      that year. Rising levels of BMI have prevented the United States from enjoying
      the full benefits of factors working to improve mortality.

PMID- 29339512
TI  - Neural preservation underlies speech improvement from auditory deprivation in
      young cochlear implant recipients.
AB  - Although cochlear implantation enables some children to attain age-appropriate
      speech and language development, communicative delays persist in others, and
      outcomes are quite variable and difficult to predict, even for children implanted
      early in life. To understand the neurobiological basis of this variability, we
      used presurgical neural morphological data obtained from MRI of individual
      pediatric cochlear implant (CI) candidates implanted younger than 3.5 years to
      predict variability of their speech-perception improvement after surgery. We
      first compared neuroanatomical density and spatial pattern similarity of CI
      candidates to that of age-matched children with normal hearing, which allowed us
      to detail neuroanatomical networks that were either affected or unaffected by
      auditory deprivation. This information enables us to build machine-learning
      models to predict the individual children's speech development following CI. We
      found that regions of the brain that were unaffected by auditory deprivation, in
      particular the auditory association and cognitive brain regions, produced the
      highest accuracy, specificity, and sensitivity in patient classification and the
      most precise prediction results. These findings suggest that brain areas
      unaffected by auditory deprivation are critical to developing closer to typical
      speech outcomes. Moreover, the findings suggest that determination of the type of
      neural reorganization caused by auditory deprivation before implantation is
      valuable for predicting post-CI language outcomes for young children.

PMID- 29339513
TI  - Projecting one's own spatial bias onto others during a theory-of-mind task.
AB  - Many people show a left-right bias in visual processing. We measured spatial bias
      in neurotypical participants using a variant of the line bisection task. In the
      same participants, we measured performance in a social cognition task. This
      theory-of-mind task measured whether each participant had a processing-speed bias
      toward the right of, or left of, a cartoon agent about which the participant was
      thinking. Crucially, the cartoon was rotated such that what was left and right
      with respect to the cartoon was up and down with respect to the participant.
      Thus, a person's own left-right bias could not align directly onto left and right
      with respect to the cartoon head. Performance on the two tasks was significantly
      correlated. People who had a natural bias toward processing their own left side
      of space were quicker to process how the cartoon might think about objects to the
      left side of its face, and likewise for a rightward bias. One possible
      interpretation of these results is that the act of processing one's own personal
      space shares some of the same underlying mechanisms as the social cognitive act
      of reconstructing someone else's processing of their space.

PMID- 29339514
TI  - Flexibility of thought in high creative individuals represented by percolation
      analysis.
AB  - Flexibility of thought is theorized to play a critical role in the ability of
      high creative individuals to generate novel and innovative ideas. However, this
      has been examined only through indirect behavioral measures. Here we use network
      percolation analysis (removal of links in a network whose strength is below an
      increasing threshold) to computationally examine the robustness of the semantic
      memory networks of low and high creative individuals. Robustness of a network
      indicates its flexibility and thus can be used to quantify flexibility of thought
      as related to creativity. This is based on the assumption that the higher the
      robustness of the semantic network, the higher its flexibility. Our analysis
      reveals that the semantic network of high creative individuals is more robust to
      network percolation compared with the network of low creative individuals and
      that this higher robustness is related to differences in the structure of the
      networks. Specifically, we find that this higher robustness is related to
      stronger links connecting between different components of similar semantic words
      in the network, which may also help to facilitate spread of activation over their
      network. Thus, we directly and quantitatively examine the relation between
      flexibility of thought and creative ability. Our findings support the associative
      theory of creativity, which posits that high creative ability is related to a
      flexible structure of semantic memory. Finally, this approach may have further
      implications, by enabling a quantitative examination of flexibility of thought,
      in both healthy and clinical populations.

PMID- 29339515
TI  - MERS-CoV and H5N1 influenza virus antagonize antigen presentation by altering the
      epigenetic landscape.
AB  - Convergent evolution dictates that diverse groups of viruses will target both
      similar and distinct host pathways to manipulate the immune response and improve
      infection. In this study, we sought to leverage this uneven viral antagonism to
      identify critical host factors that govern disease outcome. Utilizing a systems
      based approach, we examined differential regulation of IFN-gamma-dependent genes
      following infection with robust respiratory viruses including influenza viruses
      [A/influenza/Vietnam/1203/2004 (H5N1-VN1203) and A/influenza/California/04/2009
      (H1N1-CA04)] and coronaviruses [severe acute respiratory syndrome coronavirus
      (SARS-CoV) and Middle East respiratory syndrome CoV (MERS-CoV)]. Categorizing by
      function, we observed down-regulation of gene expression associated with antigen
      presentation following both H5N1-VN1203 and MERS-CoV infection. Further
      examination revealed global down-regulation of antigen-presentation gene
      expression, which was confirmed by proteomics for both H5N1-VN1203 and MERS-CoV
      infection. Importantly, epigenetic analysis suggested that DNA methylation,
      rather than histone modification, plays a crucial role in MERS-CoV-mediated
      antagonism of antigen-presentation gene expression; in contrast, H5N1-VN1203
      likely utilizes a combination of epigenetic mechanisms to target antigen
      presentation. Together, the results indicate a common mechanism utilized by H5N1
      VN1203 and MERS-CoV to modulate antigen presentation and the host adaptive immune
      response.

PMID- 29339516
TI  - Human airway branch variation and chronic obstructive pulmonary disease.
AB  - Susceptibility to chronic obstructive pulmonary disease (COPD) beyond cigarette
      smoking is incompletely understood, although several genetic variants associated
      with COPD are known to regulate airway branch development. We demonstrate that in
      vivo central airway branch variants are present in 26.5% of the general
      population, are unchanged over 10 y, and exhibit strong familial aggregation. The
      most common airway branch variant is associated with COPD in two cohorts (n =
      5,054), with greater central airway bifurcation density, and with emphysema
      throughout the lung. The second most common airway branch variant is associated
      with COPD among smokers, with narrower airway lumens in all lobes, and with
      genetic polymorphisms within the FGF10 gene. We conclude that central airway
      branch variation, readily detected by computed tomography, is a biomarker of
      widely altered lung structure with a genetic basis and represents a COPD
      susceptibility factor.

PMID- 29339517
TI  - Infected erythrocytes expressing DC13 PfEMP1 differ from recombinant proteins in
      EPCR-binding function.
AB  - Recent advances have identified a new paradigm for cerebral malaria pathogenesis
      in which endothelial protein C receptor (EPCR) is a major host receptor for
      sequestration of Plasmodium falciparum-infected erythrocytes (IEs) in the brain
      and other vital organs. The parasite adhesins that bind EPCR are members of the
      IE variant surface antigen family Plasmodium falciparum erythrocyte membrane
      protein 1 (PfEMP1) containing specific adhesion domains called domain cassette
      (DC) 8 and DC13. The binding interaction site between PfEMP1 and EPCR has been
      mapped by biophysical and crystallography studies using recombinant proteins.
      However, studies examining the interaction of native PfEMP1 on the IE surface
      with EPCR are few. We aimed to study binding to EPCR by IEs expressing DC8 and
      DC13 PfEMP1 variants whose recombinant proteins have been used in key prior
      functional and structural studies. IE binding to EPCR immobilized on plastic and
      on human brain endothelial cells was examined in static and flow adhesion assays.
      Unexpectedly, we found that IEs expressing the DC13 PfEMP1 variant HB3var03 or
      IT4var07 did not bind to EPCR on plastic and the binding of these variants to
      brain endothelial cells was not dependent on EPCR. IEs expressing the DC8 variant
      IT4var19 did bind to EPCR, but this interaction was inhibited if normal human
      serum or plasma was present, raising the possibility that IE-EPCR interaction may
      be prevented by plasma components under physiological conditions. These data
      highlight a discrepancy in EPCR-binding activity between PfEMP1 recombinant
      proteins and IEs, and indicate the critical need for further research to
      understand the pathophysiological significance of the PfEMP1-EPCR interaction.

PMID- 29339518
TI  - Iterative optimization yields Mcl-1-targeting stapled peptides with selective
      cytotoxicity to Mcl-1-dependent cancer cells.
AB  - Bcl-2 family proteins regulate apoptosis, and aberrant interactions of
      overexpressed antiapoptotic family members such as Mcl-1 promote cell
      transformation, cancer survival, and resistance to chemotherapy. Discovering
      potent and selective Mcl-1 inhibitors that can relieve apoptotic blockades is
      thus a high priority for cancer research. An attractive strategy for disabling
      Mcl-1 involves using designer peptides to competitively engage its binding
      groove, mimicking the structural mechanism of action of native sensitizer BH3
      only proteins. We transformed Mcl-1-binding peptides into alpha-helical, cell
      penetrating constructs that are selectively cytotoxic to Mcl-1-dependent cancer
      cells. Critical to the design of effective inhibitors was our introduction of an
      all-hydrocarbon cross-link or "staple" that stabilizes alpha-helical structure,
      increases target binding affinity, and independently confers binding specificity
      for Mcl-1 over related Bcl-2 family paralogs. Two crystal structures of complexes
      at 1.4 A and 1.9 A resolution demonstrate how the hydrophobic staple induces an
      unanticipated structural rearrangement in Mcl-1 upon binding. Systematic sampling
      of staple location and iterative optimization of peptide sequence in accordance
      with established design principles provided peptides that target intracellular
      Mcl-1. This work provides proof of concept for the development of potent,
      selective, and cell-permeable stapled peptides for therapeutic targeting of Mcl-1
      in cancer, applying a design and validation workflow applicable to a host of
      challenging biomedical targets.

PMID- 29339519
TI  - Evidence for convergent evolution of SINE-directed Staufen-mediated mRNA decay.
AB  - Primate-specific Alu short interspersed elements (SINEs) as well as rodent
      specific B and ID (B/ID) SINEs can promote Staufen-mediated decay (SMD) when
      present in mRNA 3'-untranslated regions (3'-UTRs). The transposable nature of
      SINEs, their presence in long noncoding RNAs, their interactions with Staufen,
      and their rapid divergence in different evolutionary lineages suggest they could
      have generated substantial modification of posttranscriptional gene-control
      networks during mammalian evolution. Some of the variation in SMD regulation
      produced by SINE insertion might have had a similar regulatory effect in separate
      mammalian lineages, leading to parallel evolution of the Staufen network by
      independent expansion of lineage-specific SINEs. To explore this possibility, we
      searched for orthologous gene pairs, each carrying a species-specific 3'-UTR SINE
      and each regulated by SMD, by measuring changes in mRNA abundance after
      individual depletion of two SMD factors, Staufen1 (STAU1) and UPF1, in both human
      and mouse myoblasts. We identified and confirmed orthologous gene pairs with 3'
      UTR SINEs that independently function in SMD control of myoblast metabolism.
      Expanding to other species, we demonstrated that SINE-directed SMD likely emerged
      in both primate and rodent lineages >20-25 million years ago. Our work reveals a
      mechanism for the convergent evolution of posttranscriptional gene regulatory
      networks in mammals by species-specific SINE transposition and SMD.

PMID- 29339520
TI  - Targeted knockout of a chemokine-like gene increases anxiety and fear responses.
AB  - Emotional responses, such as fear and anxiety, are fundamentally important
      behavioral phenomena with strong fitness components in most animal species.
      Anxiety-related disorders continue to represent a major unmet medical need in our
      society, mostly because we still do not fully understand the mechanisms of these
      diseases. Animal models may speed up discovery of these mechanisms. The zebrafish
      is a highly promising model organism in this field. Here, we report the
      identification of a chemokine-like gene family, samdori (sam), and present
      functional characterization of one of its members, sam2 We show exclusive mRNA
      expression of sam2 in the CNS, predominantly in the dorsal habenula,
      telencephalon, and hypothalamus. We found knockout (KO) zebrafish to exhibit
      altered anxiety-related responses in the tank, scototaxis and shoaling assays,
      and increased crh mRNA expression in their hypothalamus compared with wild-type
      fish. To investigate generalizability of our findings to mammals, we developed a
      Sam2 KO mouse and compared it to wild-type littermates. Consistent with zebrafish
      findings, homozygous KO mice exhibited signs of elevated anxiety. We also found
      bath application of purified SAM2 protein to increase inhibitory postsynaptic
      transmission onto CRH neurons of the paraventricular nucleus. Finally, we
      identified a human homolog of SAM2, and were able to refine a candidate gene
      region encompassing SAM2, among 21 annotated genes, which is associated with
      intellectual disability and autism spectrum disorder in the 12q14.1 deletion
      syndrome. Taken together, these results suggest a crucial and evolutionarily
      conserved role of sam2 in regulating mechanisms associated with anxiety.

PMID- 29339521
TI  - Immunogenetic novelty confers a selective advantage in host-pathogen coevolution.
AB  - The major histocompatibility complex (MHC) is crucial to the adaptive immune
      response of vertebrates and is among the most polymorphic gene families known.
      Its high diversity is usually attributed to selection imposed by fast-evolving
      pathogens. Pathogens are thought to evolve to escape recognition by common immune
      alleles, and, hence, novel MHC alleles, introduced through mutation,
      recombination, or gene flow, are predicted to give hosts superior resistance.
      Although this theoretical prediction underpins host-pathogen "Red Queen"
      coevolution, it has not been demonstrated in the context of natural MHC
      diversity. Here, we experimentally tested whether novel MHC variants (both
      alleles and functional "supertypes") increased resistance of guppies (Poecilia
      reticulata) to a common ectoparasite (Gyrodactylus turnbulli). We used exposure
      controlled infection trials with wild-sourced parasites, and Gyrodactylus-naive
      host fish that were F2 descendants of crossed wild populations. Hosts carrying
      MHC variants (alleles or supertypes) that were new to a given parasite population
      experienced a 35-37% reduction in infection intensity, but the number of MHC
      variants carried by an individual, analogous to heterozygosity in single-locus
      systems, was not a significant predictor. Our results provide direct evidence of
      novel MHC variant advantage, confirming a fundamental mechanism underpinning the
      exceptional polymorphism of this gene family and highlighting the role of
      immunogenetic novelty in host-pathogen coevolution.

PMID- 29339523
TI  - DNA synthesis from diphosphate substrates by DNA polymerases.
AB  - The activity of DNA polymerase underlies numerous biotechnologies, cell division,
      and therapeutics, yet the enzyme remains incompletely understood. We demonstrate
      that both thermostable and mesophilic DNA polymerases readily utilize
      deoxyribonucleoside diphosphates (dNDPs) for DNA synthesis and inorganic
      phosphate for the reverse reaction, that is, phosphorolysis of DNA. For Taq DNA
      polymerase, the KMs of the dNDP and phosphate substrates are ~20 and 200 times
      higher than for dNTP and pyrophosphate, respectively. DNA synthesis from dNDPs is
      about 17 times slower than from dNTPs, and DNA phosphorolysis about 200 times
      less efficient than pyrophosphorolysis. Such parameters allow DNA replication
      without requiring coupled metabolism to sequester the phosphate products, which
      consequently do not pose a threat to genome stability. This mechanism contrasts
      with DNA synthesis from dNTPs, which yield high-energy pyrophosphates that have
      to be hydrolyzed to phosphates to prevent the reverse reaction. Because the last
      common ancestor was likely a thermophile, dNDPs are plausible substrates for
      genome replication on early Earth and may represent metabolic intermediates later
      replaced by the higher-energy triphosphates.

PMID- 29339522
TI  - Effect of beta-agonists on LAM progression and treatment.
AB  - Lymphangioleiomyomatosis (LAM), a rare disease of women, is associated with
      cystic lung destruction resulting from the proliferation of abnormal smooth
      muscle-like LAM cells with mutations in the tuberous sclerosis complex (TSC)
      genes TSC1 and/or TSC2 The mutant genes and encoded proteins are responsible for
      activation of the mechanistic target of rapamycin (mTOR), which is inhibited by
      sirolimus (rapamycin), a drug used to treat LAM. Patients who have LAM may also
      be treated with bronchodilators for asthma-like symptoms due to LAM. We observed
      stabilization of forced expiratory volume in 1 s over time in patients receiving
      sirolimus and long-acting beta-agonists with short-acting rescue inhalers
      compared with patients receiving only sirolimus. Because beta-agonists increase
      cAMP and PKA activity, we investigated effects of PKA activation on the mTOR
      pathway. Human skin TSC2+/- fibroblasts or LAM lung cells incubated short-term
      with isoproterenol (beta-agonist) showed a sirolimus-independent increase in
      phosphorylation of S6, a downstream effector of the mTOR pathway, and increased
      cell growth. Cells incubated long-term with isoproterenol, which may lead to beta
      adrenergic receptor desensitization, did not show increased S6 phosphorylation.
      Inhibition of PKA blocked the isoproterenol effect on S6 phosphorylation. Thus,
      activation of PKA by beta-agonists increased phospho-S6 independent of mTOR, an
      effect abrogated by beta-agonist-driven receptor desensitization. In agreement,
      retrospective clinical data from patients with LAM suggested that a combination
      of bronchodilators in conjunction with sirolimus may be preferable to sirolimus
      alone for stabilization of pulmonary function.

PMID- 29339524
TI  - Communication in context: Interpreting promises in an experiment on competition
      and trust.
AB  - How much do people lie, and how much do people trust communication when lying is
      possible? An important step toward answering these questions is understanding how
      communication is interpreted. This paper establishes in a canonical experiment
      that competition can alter the shared communication code: the commonly understood
      meaning of messages. We study a sender-receiver game in which the sender dictates
      how to share $10 with the receiver, if the receiver participates. The receiver
      has an outside option and decides whether to participate after receiving a
      nonbinding offer from the sender. Competition for play between senders leads to
      higher offers but has no effect on actual transfers, expected transfers, or
      receivers' willingness to play. The higher offers signal that sharing will be
      equitable without the expectation that they should be followed literally: Under
      competition "6 is the new 5."

PMID- 29339525
TI  - Pulsating dissolution of crystalline matter.
AB  - Fluid-solid reactions result in material flux from or to the solid surface. The
      prediction of the flux, its variations, and changes with time are of interest to
      a wide array of disciplines, ranging from the material and earth sciences to
      pharmaceutical sciences. Reaction rate maps that are derived from sequences of
      topography maps illustrate the spatial distribution of reaction rates across the
      crystal surface. Here, we present highly spatially resolved rate maps that reveal
      the existence of rhythmic pulses of the material flux from the crystal surface.
      This observation leads to a change in our understanding of the way crystalline
      matter dissolves. Rhythmic fluctuations of the reactive surface site density and
      potentially concomitant oscillations in the fluid saturation imply spatial and
      temporal variability in surface reaction rates. Knowledge of such variability
      could aid attempts to upscale microscopic rates and predict reactive transport
      through changing porous media.

PMID- 29339526
TI  - The diversity of gestational diabetes: a therapeutic challenge.
AB  - Metformin as the first drug of choice for glucose lowering in gestational
      diabetes (GDM) is still controversial, despite recent publications reporting
      similar outcomes in comparison to insulin, both for offspring and mothers. The
      use of metformin during pregnancy is increasing and several recent guidelines
      recommend metformin use in GDM pregnancies. Background, current metformin use and
      unresolved concerns are discussed in the context of the article from Gante and
      coworkers.

PMID- 29339527
TI  - Diminished androgen and estrogen receptors and aromatase levels in hypogonadal
      diabetic men: reversal with testosterone.
AB  - AIMS: One-third of males with type 2 diabetes (T2DM) have hypogonadism,
      characterized by low total and free testosterone concentrations. We hypothesized
      that this condition is associated with a compensatory increase in the expression
      of androgen receptors (AR) and that testosterone replacement reverses these
      changes. We also measured estrogen receptor and aromatase expression. MATERIALS
      AND METHODS: This is a randomized double-blind placebo-controlled trial. Thirty
      two hypogonadal and 32 eugonadal men with T2DM were recruited. Hypogonadal men
      were randomized to receive intramuscular testosterone or saline every 2 weeks for
      22 weeks. We measured AR, ERalpha and aromatase expression in peripheral blood
      mononuclear cells (MNC), adipose tissue and skeletal muscle in hypogonadal and
      eugonadal males with T2DM at baseline and after 22 weeks of treatment in those
      with hypogonadism. RESULTS: The mRNA expression of AR, ERalpha (ESR1) and
      aromatase in adipose tissue from hypogonadal men was significantly lower as
      compared to eugonadal men, and it increased significantly to levels comparable to
      those in eugonadal patients with T2DM following testosterone treatment. AR mRNA
      expression was also significantly lower in MNC from hypogonadal patients compared
      to eugonadal T2DM patients. Testosterone administration in hypogonadal patients
      also restored AR mRNA and nuclear extract protein levels from MNC to that in
      eugonadal patients. In the skeletal muscle, AR mRNA and protein expression are
      lower in men with hypogonadism. Testosterone treatment restored AR expression
      levels to that comparable to levels in eugonadal men. CONCLUSIONS: We conclude
      that, contrary to our hypothesis, the expression of AR, ERalpha and aromatase is
      significantly diminished in hypogonadal men as compared to eugonadal men with
      type 2 diabetes. Following testosterone replacement, there is a reversal of these
      deficits.

PMID- 29339529
TI  - MANAGEMENT OF ENDOCRINE DISEASE: Atypical femoral fractures: risks and benefits
      of long-term treatment of osteoporosis with anti-resorptive therapy.
AB  - Modern osteoporosis treatment began in the mid-1990s with the approval of amino
      bisphosphonates, anti-resorptive agents that have been shown to decrease
      osteoporotic fracture risk by about half. In 2005, the first cases of atypical
      femoral fractures (AFF), occurring in the shaft of the femur, were reported.
      Since then, more cases have been found, leading to great concern among patients
      and a dramatic decrease in bisphosphonate prescribing. The pathogenesis and
      incidence of AFF are reviewed herein. Management and an approach to prevention or
      early detection of AFF are also provided. Denosumab, a more recently approved
      anti-resorptive medication has also been associated with AFF. Long-term
      management of osteoporosis and prevention of fracture are challenging in light of
      this serious but uncommon side effect, yet with an aging population osteoporotic
      fracture is destined to increase in frequency.

PMID- 29339528
TI  - Gonadal function in adult male patients with congenital adrenal hyperplasia.
AB  - CONTEXT: Current knowledge on gonadal function in congenital adrenal hyperplasia
      (CAH) is mostly limited to single-center/country studies enrolling small patient
      numbers. Overall data indicate that gonadal function can be compromised in men
      with CAH. OBJECTIVE: To determine gonadal function in men with CAH within the
      European 'dsd-LIFE' cohort. DESIGN: Cross-sectional clinical outcome study,
      including retrospective data from medical records. METHODS: Fourteen academic
      hospitals included 121 men with CAH aged 16-68 years. Main outcome measures were
      serum hormone concentrations, semen parameters and imaging data of the testes.
      RESULTS: At the time of assessment, 14/69 patients had a serum testosterone
      concentration below the reference range; 7 of those were hypogonadotropic, 6
      normogonadotropic and 1 hypergonadotropic. In contrast, among the patients with
      normal serum testosterone (55/69), 4 were hypogonadotropic, 44 normogonadotropic
      and 7 hypergonadotropic. The association of decreased testosterone with reduced
      gonadotropin concentrations (odds ratio (OR) = 12.8 (2.9-57.3)) was weaker than
      the association between serum androstenedione/testosterone ratio >=1 and reduced
      gonadotropin concentrations (OR = 39.3 (2.1-732.4)). Evaluation of sperm quality
      revealed decreased sperm concentrations (15/39), motility (13/37) and abnormal
      morphology (4/28). Testicular adrenal rest tumor (TART)s were present in 39/80
      patients, with a higher prevalence in patients with the most severe genotype
      (14/18) and in patients with increased current 17-hydroxyprogesterone 20/35) or
      androstenedione (12/18) serum concentrations. Forty-three children were fathered
      by 26/113 patients. CONCLUSIONS: Men with CAH have a high risk of developing
      hypothalamic-pituitary-gonadal disturbances and spermatogenic abnormalities.
      Regular assessment of endocrine gonadal function and imaging for TART development
      are recommended, in addition to measures for fertility protection.

PMID- 29339530
TI  - MANAGEMENT OF ENDOCRINE DISEASE: Personalized medicine in the treatment of
      acromegaly.
AB  - Acromegaly is associated with high morbidity and elevated mortality when not
      adequately treated. Surgery is the first-line treatment for most patients as it
      is the only one that can lead to immediate cure. In patients who are not cured by
      surgery, treatment is currently based on a trial-and-error approach. First
      generation somatostatin receptor ligands (fg-SRL) are initiated for most
      patients, although approximately 25% of patients present resistance to this drug
      class. Some biomarkers of treatment outcome are described in the literature, with
      the aim of categorizing patients into different groups to individualize their
      treatments using a personalized approach. In this review, we will discuss the
      current status of precision medicine for the treatment of acromegaly and future
      perspectives on the use of personalized medicine for this purpose.

PMID- 29339531
TI  - EMA calls for hydroxyethyl starch solutions to be taken off market.

PMID- 29339532
TI  - Football headers and dementia: five minutes with Willie Stewart.

PMID- 29339533
TI  - Learning-dependent chromatin remodeling highlights noncoding regulatory regions
      linked to autism.
AB  - Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder that is
      associated with genetic risk factors. Most human disease-associated single
      nucleotide polymorphisms (SNPs) are not located in genes but rather are in
      regulatory regions that control gene expression. The function of regulatory
      regions is determined through epigenetic mechanisms. Parallels between the
      cellular basis of development and the formation of long-term memory have long
      been recognized, particularly the role of epigenetic mechanisms in both
      processes. We analyzed how learning alters chromatin accessibility in the mouse
      hippocampus using a new high-throughput sequencing bioinformatics strategy we
      call DEScan (differential enrichment scan). DEScan, which enabled the analysis of
      data from epigenomic experiments containing multiple replicates, revealed changes
      in chromatin accessibility at 2365 regulatory regions-most of which were
      promoters. Learning-regulated promoters were active during forebrain development
      in mice and were enriched in epigenetic modifications indicative of bivalent
      promoters. These promoters were disproportionally intronic, showed a complex
      relationship with gene expression and alternative splicing during memory
      consolidation and retrieval, and were enriched in the data set relative to known
      ASD risk genes. Genotyping in a clinical cohort within one of these promoters
      (SHANK3 promoter 6) revealed that the SNP rs6010065 was associated with ASD. Our
      data support the idea that learning recapitulates development at the epigenetic
      level and demonstrate that behaviorally induced epigenetic changes in mice can
      highlight regulatory regions relevant to brain disorders in patients.

PMID- 29339535
TI  - Functional changes of AMPA responses in human induced pluripotent stem cell
      derived neural progenitors in fragile X syndrome.
AB  - Altered neuronal network formation and function involving dysregulated excitatory
      and inhibitory circuits are associated with fragile X syndrome (FXS). We examined
      functional maturation of the excitatory transmission system in FXS by
      investigating the response of FXS patient-derived neural progenitor cells to the
      glutamate analog (AMPA). Neural progenitors derived from induced pluripotent stem
      cell (iPSC) lines generated from boys with FXS had augmented intracellular Ca2+
      responses to AMPA and kainate that were mediated by Ca2+-permeable AMPA receptors
      (CP-AMPARs) lacking the GluA2 subunit. Together with the enhanced differentiation
      of glutamate-responsive cells, the proportion of CP-AMPAR and N-methyl-d
      aspartate (NMDA) receptor-coexpressing cells was increased in human FXS
      progenitors. Differentiation of cells lacking GluA2 was also increased and
      paralleled the increased inward rectification in neural progenitors derived from
      Fmr1-knockout mice (the FXS mouse model). Human FXS progenitors had increased the
      expression of the precursor and mature forms of miR-181a, a microRNA that
      represses translation of the transcript encoding GluA2. Blocking GluA2-lacking,
      CP-AMPARs reduced the neurite length of human iPSC-derived control progenitors
      and further reduced the shortened length of neurites in human FXS progenitors,
      supporting the contribution of CP-AMPARs to the regulation of progenitor
      differentiation. Furthermore, we observed reduced expression of Gria2 (the GluA2
      encoding gene) in the frontal lobe of FXS mice, consistent with functional
      changes of AMPARs in FXS. Increased Ca2+ influx through CP-AMPARs may increase
      the vulnerability and affect the differentiation and migration of distinct cell
      populations, which may interfere with normal circuit formation in FXS.

PMID- 29339534
TI  - Inactivating mutations in Drosha mediate vascular abnormalities similar to
      hereditary hemorrhagic telangiectasia.
AB  - The transforming growth factor-beta (TGF-beta) and bone morphogenetic protein
      (BMP) family of cytokines critically regulates vascular morphogenesis and
      homeostasis. Impairment of TGF-beta or BMP signaling leads to heritable vascular
      disorders, including hereditary hemorrhagic telangiectasia (HHT). Drosha, a key
      enzyme for microRNA (miRNA) biogenesis, also regulates the TGF-beta and BMP
      pathway through interaction with Smads and their joint control of gene expression
      through miRNAs. We report that mice lacking Drosha in the vascular endothelium
      developed a vascular phenotype resembling HHT that included dilated and
      disorganized vasculature, arteriovenous fistulae, and hemorrhages. Exome
      sequencing of HHT patients who lacked known pathogenic mutations revealed an
      overrepresentation of rare nonsynonymous variants of DROSHA Two of these DROSHA
      variants (P100L and R279L) did not interact with Smads and were partially
      catalytically active. In zebrafish, expression of these mutants or morpholino
      directed knockdown of Drosha resulted in angiogenesis defects and abnormal
      vascular permeability. Together, our studies point to an essential role of Drosha
      in vascular development and the maintenance of vascular integrity, and reveal a
      previously unappreciated link between Drosha dysfunction and HHT.

PMID- 29339536
TI  - Length of Stay and Hospital Revisit After Bacterial Tracheostomy-Associated
      Respiratory Tract Infection Hospitalizations.
AB  - OBJECTIVES: To identify factors associated with longer length of stay (LOS) and
      higher 30-day hospital revisit rates for children hospitalized with bacterial
      tracheostomy-associated respiratory tract infections (bTARTIs). METHODS: This was
      a multicenter, retrospective cohort study using administrative data from the
      Pediatric Health Information System database between 2007 and 2014 of patients 30
      days to 17 years old with a principal discharge diagnosis of bTARTI or a
      principal discharge diagnosis of bTARTI symptoms with a secondary diagnosis of
      bTARTI. Primary outcomes of LOS (in days) and 30-day all-cause revisit rates
      (inpatient, observation, or emergency department visit) were analyzed by using a
      3-level hierarchical regression model (discharges within patients within
      hospital). RESULTS: We included 3715 unique patients and 7355 discharges. The
      median LOS was 4 days (interquartile range: 3-8 days), and the 30-day revisit
      rate was 30.5%. Compared with children 1 to 4 years old, children aged 30 days to
      12 months had both longer LOS (adjusted length of stay [aLOS] = +0.9 days; 95%
      confidence interval [CI]: 0.6 to 1.3) and increased hospital revisit risk
      (adjusted odds ratio [aOR] = 1.5; 95% CI: 1.3 to 1.7). Other factors associated
      with longer LOS included public insurance (aLOS = +0.5 days; 95% CI: 0.2 to 0.8),
      3 or more complex chronic conditions (CCCs), mechanical ventilation (acute or
      chronic), and empirical anti-Pseudomonas aeruginosa antibiotics (aLOS = +0.6
      days; 95% CI: 0.3 to 0.9). Other factors associated with 30-day revisit included
      4 or more CCCs (aOR = 1.3; 95% CI: 1.1 to 1.6) and chronic ventilator dependency
      (aOR = 1.1; 95% CI: 1.0 to 1.3). CONCLUSIONS: Ventilator-dependent patients <12
      months old with at least 4 CCCs are at highest risk for both longer LOS and 30
      day revisit after discharge for bTARTIs. They may benefit from bTARTI prevention
      strategies and intensive care coordination while hospitalized.

PMID- 29339537
TI  - STAT3/PIAS3 Levels Serve as "Early Signature" Genes in the Development of High
      Grade Serous Carcinoma from the Fallopian Tube.
AB  - The initial molecular events that lead to malignant transformation of the fimbria
      of the fallopian tube (FT) through high-grade serous ovarian carcinoma (HGSC)
      remain poorly understood. In this study, we report that increased expression of
      signal transducer and activator of transcription 3 (pSTAT3 Tyr705) and
      suppression or loss of protein inhibitor of activated STAT3 (PIAS3) in FT likely
      drive HGSC. We evaluated human tissues-benign normal FT, tubal-peritoneal
      junction (TPJ), p53 signature FT tissue, tubal intraepithelial lesion in
      transition (TILT), serous tubal intraepithelial carcinoma (STIC) without ovarian
      cancer, and HGSC for expression of STAT3/PIAS3 (compared with their known TP53
      signature) and their target proliferation genes. We observed constitutive
      activation of STAT3 and low levels or loss of PIAS3 in the TPJ, p53 signature,
      TILT, and STIC through advanced stage IV (HGSC) tissues. Elevated expression of
      pSTAT3 Tyr705 and decreased levels of PIAS3 appeared as early as TPJ and the
      trend continued until very advanced stage HGSC (compared with high PIAS3 and low
      pSTAT3 expression in normal benign FT). Exogenous expression of STAT3 in FT cells
      mediated translocation of pSTAT3 and c-Myc into the nucleus. In vivo experiments
      demonstrated that overexpression of STAT3 in FT secretory epithelial cells
      promoted tumor progression and metastasis, mimicking the clinical disease
      observed in patients with HGSC. Thus, we conclude that the STAT3 pathway plays a
      role in the development and progression of HGSC from its earliest premalignant
      states.Significance: Concomitant gain of pSTAT3 Tyr705 and loss of PIAS3 appear
      critical for initiation and development of high-grade serous carcinoma. Cancer
      Res; 78(7); 1739-50. (c)2018 AACR.

PMID- 29339538
TI  - E6 Protein Expressed by High-Risk HPV Activates Super-Enhancers of the EGFR and c
      MET Oncogenes by Destabilizing the Histone Demethylase KDM5C.
AB  - The high-risk (HR) human papillomaviruses (HPV) are causative agents of
      anogenital tract dysplasia and cancers and a fraction of head and neck cancers.
      The HR HPV E6 oncoprotein possesses canonical oncogenic functions, such as p53
      degradation and telomerase activation. It is also capable of stimulating
      expression of several oncogenes, but the molecular mechanism underlying these
      events is poorly understood. Here, we provide evidence that HPV16 E6 physically
      interacts with histone H3K4 demethylase KDM5C, resulting in its degradation in an
      E3 ligase E6AP- and proteasome-dependent manner. Moreover, we found that HPV16
      positive cancer cell lines exhibited lower KDM5C protein levels than HPV-negative
      cancer cell lines. Restoration of KDM5C significantly suppressed the
      tumorigenicity of CaSki cells, an HPV16-positive cervical cancer cell line. Whole
      genome ChIP-seq and RNA-seq results revealed that CaSki cells contained super
      enhancers in the proto-oncogenes EGFR and c-MET Ectopic KDM5C dampened these
      super-enhancers and reduced the expression of proto-oncogenes. This effect was
      likely mediated by modulating H3K4me3/H3K4me1 dynamics and decreasing
      bidirectional enhancer RNA transcription. Depletion of KDM5C or HPV16 E6
      expression activated these two super-enhancers. These results illuminate a
      pivotal relationship between the oncogenic E6 proteins expressed by HR HPV
      isotypes and epigenetic activation of super-enhancers in the genome that drive
      expression of key oncogenes like EGFR and c-METSignificance: This study suggests
      a novel explanation for why infections with certain HPV isotypes are associated
      with elevated cancer risk by identifying an epigenetic mechanism through which E6
      proteins expressed by those isotypes can drive expression of key oncogenes.
      Cancer Res; 78(6); 1418-30. (c)2018 AACR.

PMID- 29339539
TI  - The Hippo Pathway Component TAZ Promotes Immune Evasion in Human Cancer through
      PD-L1.
AB  - The Hippo pathway component WW domain-containing transcription regulator 1 (TAZ)
      is a transcriptional coactivator and an oncogene in breast and lung cancer.
      Transcriptional targets of TAZ that modulate immune cell function in the tumor
      microenvironment are poorly understood. Here, we perform a comprehensive screen
      for immune-related genes regulated by TAZ and its paralog YAP using NanoString
      gene expression profiling. We identify the immune checkpoint molecule PD-L1 as a
      target of Hippo signaling. The upstream kinases of the Hippo pathway, mammalian
      STE20-like kinase 1 and 2 (MST1/2), and large tumor suppressor 1 and 2 (LATS1/2),
      suppress PD-L1 expression while TAZ and YAP enhance PD-L1 levels in breast and
      lung cancer cell lines. PD-L1 expression in cancer cell lines is determined by
      TAZ activity and TAZ/YAP/TEAD increase PD-L1 promoter activity. Critically, TAZ
      induced PD-L1 upregulation in human cancer cells is sufficient to inhibit T-cell
      function. The relationship between TAZ and PD-L1 is not conserved in multiple
      mouse cell lines, likely due to differences between the human and mouse PD-L1
      promoters. To explore the extent of divergence in TAZ immune-related targets
      between human and mouse cells, we performed a second NanoString screen using
      mouse cell lines. We show that many targets of TAZ may be differentially
      regulated between these species. These findings highlight the role of Hippo
      signaling in modifying human/murine physiologic/pathologic immune responses and
      provide evidence implicating TAZ in human cancer immune evasion.Significance:
      Human-specific activation of PD-L1 by a novel Hippo signaling pathway in cancer
      immune evasion may have a significant impact on research in immunotherapy. Cancer
      Res; 78(6); 1457-70. (c)2018 AACR.

PMID- 29339540
TI  - Radioresistant Cervical Cancers Are Sensitive to Inhibition of Glycolysis and
      Redox Metabolism.
AB  - Highly glycolytic cervical cancers largely resist treatment by cisplatin and
      coadministered pelvic irradiation as the present standard of care. In this study,
      we investigated the effects of inhibiting glycolysis and thiol redox metabolism
      to evaluate them as alternate treatment strategies in these cancers. In a panel
      of multiple cervical cancer cell lines, we evaluated sensitivity to inhibition of
      glycolysis (2-deoxyglucose, 2-DG) with or without simultaneous inhibition of
      glutathione and thioredoxin metabolism (BSO/AUR). Intracellular levels of total
      and oxidized glutathione, thioredoxin reductase activity, and indirect measures
      of intracellular reactive oxygen species were compared before and after
      treatment. Highly radioresistant cells were the most sensitive to 2-DG, whereas
      intermediate radioresistant cells were sensitive to 2-DG plus BSO/AUR. In
      response to 2-DG/BSO/AUR treatment, we observed increased levels of intracellular
      oxidized glutathione, redox-sensitive dye oxidation, and decreased glucose
      utilization via multiple metabolic pathways including the tricarboxylic acid
      cycle. 2-DG/BSO/AUR treatment delayed the growth of tumors composed of
      intermediate radioresistant cells and effectively radiosensitized these tumors at
      clinically relevant radiation doses both in vitro and in vivo Overall, our
      results support inhibition of glycolysis and intracellular redox metabolism as an
      effective alternative drug strategy for the treatment of highly glycolytic and
      radioresistant cervical cancers.Significance: This study suggests a simple
      metabolic approach to strike at an apparent Achilles' heel in highly glycolytic,
      radioresistant forms of cervical cancers, possibly with broader applications in
      cancer therapy. Cancer Res; 78(6); 1392-403. (c)2018 AACR.

PMID- 29339541
TI  - PHD3 Controls Lung Cancer Metastasis and Resistance to EGFR Inhibitors through
      TGFalpha.
AB  - Lung cancer is the leading cause of cancer-related death worldwide, in large part
      due to its high propensity to metastasize and to develop therapy resistance.
      Adaptive responses to hypoxia and epithelial-mesenchymal transition (EMT) are
      linked to tumor metastasis and drug resistance, but little is known about how
      oxygen sensing and EMT intersect to control these hallmarks of cancer. Here, we
      show that the oxygen sensor PHD3 links hypoxic signaling and EMT regulation in
      the lung tumor microenvironment. PHD3 was repressed by signals that induce EMT
      and acted as a negative regulator of EMT, metastasis, and therapeutic resistance.
      PHD3 depletion in tumors, which can be caused by the EMT inducer TGFbeta or by
      promoter methylation, enhanced EMT and spontaneous metastasis via HIF-dependent
      upregulation of the EGFR ligand TGFalpha. In turn, TGFalpha stimulated EGFR,
      which potentiated SMAD signaling, reinforcing EMT and metastasis. In clinical
      specimens of lung cancer, reduced PHD3 expression was linked to poor prognosis
      and to therapeutic resistance against EGFR inhibitors such as erlotinib.
      Reexpression of PHD3 in lung cancer cells suppressed EMT and metastasis and
      restored sensitivity to erlotinib. Taken together, our results establish a key
      function for PHD3 in metastasis and drug resistance and suggest opportunities to
      improve patient treatment by interfering with the feedforward signaling
      mechanisms activated by PHD3 silencing.Significance: This study links the oxygen
      sensor PHD3 to metastasis and drug resistance in cancer, with implications for
      therapeutic improvement by targeting this system. Cancer Res; 78(7); 1805-19.
      (c)2018 AACR.

PMID- 29339542
TI  - AMPK-Akt Double-Negative Feedback Loop in Breast Cancer Cells Regulates Their
      Adaptation to Matrix Deprivation.
AB  - Cell detachment from the extracellular matrix triggers anoikis. Disseminated
      tumor cells must adapt to survive matrix deprivation, while still retaining the
      ability to attach at secondary sites and reinitiate cell division. In this study,
      we elucidate mechanisms that enable reversible matrix attachment by breast cancer
      cells. Matrix deprival triggered AMPK activity and concomitantly inhibited AKT
      activity by upregulating the Akt phosphatase PHLPP2. The resultant
      pAMPKhigh/pAktlow state was critical for cell survival in suspension, as PHLPP2
      silencing also increased anoikis while impairing autophagy and metastasis. In
      contrast, matrix reattachment led to Akt-mediated AMPK inactivation via PP2C
      alpha-mediated restoration of the pAkthigh/pAMPKlow state. Clinical specimens of
      primary and metastatic breast cancer displayed an Akt-associated gene expression
      signature, whereas circulating breast tumor cells displayed an elevated AMPK
      dependent gene expression signature. Our work establishes a double-negative
      feedback loop between Akt and AMPK to control the switch between matrix-attached
      and matrix-detached states needed to coordinate cell growth and survival during
      metastasis.Significance: These findings reveal a molecular switch that regulates
      cancer cell survival during metastatic dissemination, with the potential to
      identify targets to prevent metastasis in breast cancer. Cancer Res; 78(6); 1497
      510. (c)2018 AACR.

PMID- 29339543
TI  - Genes Predisposed to DNA Hypermethylation during Acquired Resistance to
      Chemotherapy Are Identified in Ovarian Tumors by Bivalent Chromatin Domains at
      Initial Diagnosis.
AB  - Bivalent chromatin domains containing both active H3K4me3 and repressive H3K27me3
      histone marks define gene sets poised for expression or silencing in
      differentiating embryonic stem (ES) cells. In cancer cells, aberrantly poised
      genes may facilitate changes in transcriptional states after exposure to
      anticancer drugs. In this study, we used ChIP-seq to characterize genome-wide
      positioning of H3K4me3- and H3K27me3-associated chromatin in primary high-grade
      serous ovarian carcinomas and in normal ovarian surface and fallopian tube
      tissue. Gene sets with proximal bivalent marks defined in this manner were
      evaluated subsequently as signatures of systematic change in DNA methylation and
      gene expression, comparing pairs of tissue samples taken from patients at primary
      presentation and relapse following chemotherapy. We found that gene sets
      harboring bivalent chromatin domains at their promoters in tumor tissue, but not
      normal epithelia, overlapped with Polycomb-repressive complex target genes as
      well as transcriptionally silenced genes in normal ovarian and tubal stem cells.
      The bivalently marked genes we identified in tumors before chemotherapy displayed
      increased promoter CpG methylation and reduced gene expression at relapse after
      chemotherapy of ovarian cancer. Overall, our results support the hypothesis that
      preexisting histone modifications at genes in a poised chromatin state may lead
      to epigenetic silencing during acquired drug resistance.Significance: These
      results suggest epigenetic targets for intervention to prevent the emergence of
      cancer drug resistance. Cancer Res; 78(6); 1383-91. (c)2018 AACR.

PMID- 29339544
TI  - Role of Chromatin Damage and Chromatin Trapping of FACT in Mediating the
      Anticancer Cytotoxicity of DNA-Binding Small-Molecule Drugs.
AB  - Precisely how DNA-targeting chemotherapeutic drugs trigger cancer cell death
      remains unclear, as it is difficult to separate direct DNA damage from other
      effects in cells. Recent work on curaxins, a class of small-molecule drugs with
      broad anticancer activity, shows that they interfere with histone-DNA
      interactions and destabilize nucleosomes without causing detectable DNA damage.
      Chromatin damage caused by curaxins is sensed by the histone chaperone FACT,
      which binds unfolded nucleosomes becoming trapped in chromatin. In this study, we
      investigated whether classical DNA-targeting chemotherapeutic drugs also
      similarly disturbed chromatin to cause chromatin trapping of FACT (c-trapping).
      Drugs that directly bound DNA induced both chromatin damage and c-trapping.
      However, chromatin damage occurred irrespective of direct DNA damage and was
      dependent on how a drug bound DNA, specifically, in the way it bound
      chromatinized DNA in cells. FACT was sensitive to a plethora of nucleosome
      perturbations induced by DNA-binding small molecules, including displacement of
      the linker histone, eviction of core histones, and accumulation of negative
      supercoiling. Strikingly, we found that the cytotoxicity of DNA-binding small
      molecules correlated with their ability to cause chromatin damage, not DNA
      damage. Our results suggest implications for the development of chromatin
      damaging agents as selective anticancer drugs.Significance: These provocative
      results suggest that the anticancer efficacy of traditional DNA-targeting
      chemotherapeutic drugs may be based in large part on chromatin damage rather than
      direct DNA damage. Cancer Res; 78(6); 1431-43. (c)2018 AACR.

PMID- 29339545
TI  - Perioperative Implementation of Noninvasive Positive Airway Pressure Therapies.
AB  - Noninvasively applied positive airway pressure therapy (PAP) is available in 3
      basic modes: continuous positive airway pressure (CPAP), bi-level positive airway
      pressure (BPAP), and adaptive servo-ventilation. These are in widespread use in
      home and hospital settings to treat a variety of disorders of ventilation or gas
      exchange, including obstructive sleep apnea, sleep-related hypoventilation,
      periodic breathing, acute and chronic hypercapnic respiratory failure, and acute
      respiratory failure. They are increasingly being used perioperatively to prevent
      or treat upper airway obstruction, hypoventilation, and periodic breathing, and
      they have been found to improve postoperative outcomes in the case of obstructive
      sleep apnea. An impediment to their use in this setting is a lack of familiarity
      with their application by hospital clinical staff. This review describes the
      modes of PAP therapy available, their indications, how therapy is initiated, how
      efficacy is assessed, common problems encountered with its use, and how these
      problems can be addressed.

PMID- 29339546
TI  - Correction: Interventions that improve maternity care for immigrant women in the
      UK: protocol for a narrative synthesis systematic review.

PMID- 29339547
TI  - Opinion: Measuring how countries adapt to societal aging.

PMID- 29339549
TI  - APOL1 Genotype and Renal Function of Black Living Donors.
AB  - Black living kidney donors are at higher risk of developing kidney disease than
      white donors. We examined the effect of the APOL1 high-risk genotype on
      postdonation renal function in black living kidney donors and evaluated whether
      this genotype alters the association between donation and donor outcome. We
      grouped 136 black living kidney donors as APOL1 high-risk (two risk alleles;
      n=19; 14%) or low-risk (one or zero risk alleles; n=117; 86%) genotype.
      Predonation characteristics were similar between groups, except for lower mean+/
      SD baseline eGFR (CKD-EPI equation) in donors with the APOL1 high-risk genotype
      (98+/-17 versus 108+/-20 ml/min per 1.73 m2; P=0.04). At a median of 12 years
      after donation, donors with the APOL1 high-risk genotype had lower eGFR (57+/-18
      versus 67+/-15 ml/min per 1.73 m2; P=0.02) and faster decline in eGFR after
      adjusting for predonation eGFR (1.19; 95% confidence interval, 0 to 2.3 versus
      0.4; 95% confidence interval, 0.1 to 0.7 ml/min per 1.73 m2 per year, P=0.02).
      Two donors developed ESRD; both carried the APOL1 high-risk genotype. In a
      subgroup of 115 donors matched to 115 nondonors by APOL1 genotype, we did not
      find a difference between groups in the rate of eGFR decline (P=0.39) or any
      statistical interaction by APOL1 status (P=0.92). In conclusion, APOL1 high-risk
      genotype in black living kidney donors associated with greater decline in
      postdonation kidney function. Trajectory of renal function was similar between
      donors and nondonors. The association between APOL1 high-risk genotype and poor
      renal outcomes in kidney donors requires validation in a larger study.

PMID- 29339550
TI  - Relative Target Affinities of T-Cell-Dependent Bispecific Antibodies Determine
      Biodistribution in a Solid Tumor Mouse Model.
AB  - Anti-HER2/CD3, a T-cell-dependent bispecific antibody (TDB) construct, induces T
      cell-mediated cell death in cancer cells expressing HER2 by cross-linking tumor
      HER2 with CD3 on cytotoxic T cells, thereby creating a functional cytolytic
      synapse. TDB design is a very challenging process that requires consideration of
      multiple parameters. Although therapeutic antibody design strategy is commonly
      driven by striving for the highest attainable antigen-binding affinity, little is
      known about how the affinity of each TDB arm can affect the targeting ability of
      the other arm and the consequent distribution and efficacy. To our knowledge, no
      distribution studies have been published using preclinical models wherein the T
      cell-targeting arm of the TDB is actively bound to T cells. We used a combined
      approach involving radiochemistry, invasive biodistribution, and noninvasive
      single-photon emission tomographic (SPECT) imaging to measure TDB distribution
      and catabolism in transgenic mice with human CD3epsilon expression on T cells.
      Using CD3 affinity variants, we assessed the impact of CD3 affinity on short-term
      pharmacokinetics, tissue distribution, and cellular uptake. Our experimental
      approach determined the relative effects of (i) CD3 targeting to normal tissues,
      (ii) HER2 targeting to HER2-expressing tumors, and (iii) relative HER2/CD3
      affinity, all as critical drivers for TDB distribution. We observed a strong
      correlation between CD3 affinity and distribution to T-cell-rich tissues, with
      higher CD3 affinity reducing systemic exposure and shifting TDB distribution away
      from tumor to T-cell-containing tissues. These observations have important
      implications for clinical translation of bispecific antibodies for cancer
      immunotherapy. Mol Cancer Ther; 17(4); 776-85. (c)2018 AACR.

PMID- 29339551
TI  - Inhibition of FLT3 and PIM Kinases by EC-70124 Exerts Potent Activity in
      Preclinical Models of Acute Myeloid Leukemia.
AB  - Internal tandem duplication (ITD) or tyrosine kinase domain mutations of FLT3 is
      the most frequent genetic alteration in acute myelogenous leukemia (AML) and are
      associated with poor disease outcome. Despite considerable efforts to develop
      single-target FLT3 drugs, so far, the most promising clinical response has been
      achieved using the multikinase inhibitor midostaurin. Here, we explore the
      activity of the indolocarbazole EC-70124, from the same chemical space as
      midostaurin, in preclinical models of AML, focusing on those bearing FLT3-ITD
      mutations. EC-70124 potently inhibits wild-type and mutant FLT3, and also other
      important kinases such as PIM kinases. EC-70124 inhibits proliferation of AML
      cell lines, inducing cell-cycle arrest and apoptosis. EC-70124 is orally
      bioavailable and displays higher metabolic stability and lower human protein
      plasma binding compared with midostaurin. Both in vitro and in vivo
      pharmacodynamic analyses demonstrate inhibition of FLT3-STAT5, Akt-mTOR-S6, and
      PIM-BAD pathways. Oral administration of EC-70124 in FLT3-ITD xenograft models
      demonstrates high efficacy, reaching complete tumor regression. Ex vivo, EC-70124
      impaired cell viability in leukemic blasts, especially from FLT3-ITD patients.
      Our results demonstrate the ability of EC-70124 to reduce proliferation and
      induce cell death in AML cell lines, patient-derived leukemic blast and xenograft
      animal models, reaching best results in FLT3 mutants that carry other molecular
      pathways' alterations. Thus, its unique inhibition profile warrants EC-70124 as a
      promising agent for AML treatment based on its ability to interfere the complex
      oncogenic events activated in AML at several levels. Mol Cancer Ther; 17(3); 614
      24. (c)2018 AACR.

PMID- 29339552
TI  - Mechanisms of redox metabolism and cancer cell survival during extracellular
      matrix detachment.
AB  - Nontransformed cells that become detached from the extracellular matrix (ECM)
      undergo dysregulation of redox homeostasis and cell death. In contrast, cancer
      cells often acquire the ability to mitigate programmed cell death pathways and
      recalibrate the redox balance to survive after ECM detachment, facilitating
      metastatic dissemination. Accordingly, recent studies of the mechanisms by which
      cancer cells overcome ECM detachment-induced metabolic alterations have focused
      on mechanisms in redox homeostasis. The insights into these mechanisms may inform
      the development of therapeutics that manipulate redox homeostasis to eliminate
      ECM-detached cancer cells. Here, we review how ECM-detached cancer cells balance
      redox metabolism for survival.

PMID- 29339553
TI  - Engineering abiotic stress response in plants for biomass production.
AB  - One of the major challenges in today's agriculture is to achieve enhanced plant
      growth and biomass even under adverse environmental conditions. Recent
      advancements in genetics and molecular biology have enabled the identification of
      a complex signaling network contributing toward plant growth and development on
      the one hand and abiotic stress response on the other hand. As an outcome of
      these studies, three major approaches have been identified as having the
      potential to improve biomass production in plants under abiotic stress
      conditions. These approaches deal with having changes in the following: (i) plant
      microbe interactions; (ii) cell wall biosynthesis; and (iii) phytohormone levels.
      At the same time, employing functional genomics and genetics-based approaches, a
      very large number of genes have been identified that play a key role in abiotic
      stress tolerance. Our Minireview is an attempt to unveil the cross-talk that has
      just started to emerge between the transcriptional circuitries for biomass
      production and abiotic stress response. This knowledge may serve as a valuable
      resource to eventually custom design the crop plants for higher biomass
      production, in a more sustainable manner, in marginal lands under variable
      climatic conditions.

PMID- 29339554
TI  - Synthetic biology strategies for improving microbial synthesis of "green"
      biopolymers.
AB  - Polysaccharide-based biopolymers have many material properties relevant to
      industrial and medical uses, including as drug delivery agents, wound-healing
      adhesives, and food additives and stabilizers. Traditionally, polysaccharides are
      obtained from natural sources. Microbial synthesis offers an attractive
      alternative for sustainable production of tailored biopolymers. Here, we review
      synthetic biology strategies for select "green" biopolymers: cellulose, alginate,
      chitin, chitosan, and hyaluronan. Microbial production pathways, opportunities
      for pathway yield improvements, and advances in microbial engineering of
      biopolymers in various hosts are discussed. Taken together, microbial engineering
      has expanded the repertoire of green biological chemistry by increasing the
      diversity of biobased materials.

PMID- 29339555
TI  - The redox requirements of proliferating mammalian cells.
AB  - Cell growth and division require nutrients, and proliferating cells use a variety
      of sources to acquire the amino acids, lipids, and nucleotides that support
      macromolecule synthesis. Lipids are more reduced than other nutrients, whereas
      nucleotides and amino acids are typically more oxidized. Cells must therefore
      generate reducing and oxidizing (redox) equivalents to convert consumed nutrients
      into biosynthetic precursors. To that end, redox cofactor metabolism plays a
      central role in meeting cellular redox requirements. In this Minireview, we
      highlight the biosynthetic pathways that involve redox reactions and discuss
      their integration with metabolism in proliferating mammalian cells.

PMID- 29339556
TI  - Evidence of a sequestered imine intermediate during reduction of nitrile to amine
      by the nitrile reductase QueF from Escherichia coli.
AB  - In the biosynthesis of the tRNA-inserted nucleoside queuosine, the nitrile
      reductase QueF catalyzes conversion of 7-cyano-7-deazaguanine (preQ0) to 7
      aminomethyl-7-deazaguanine (preQ1), a biologically unique four-electron reduction
      of a nitrile to an amine. The QueF mechanism involves a covalent thioimide adduct
      between the enzyme and preQ0 that undergoes reduction to preQ1 in two NADPH
      dependent steps, presumably via an imine intermediate. Protecting a labile imine
      from interception by water is fundamental to QueF catalysis for proper enzyme
      function. In the QueF from Escherichia coli, the conserved Glu89 and Phe228
      residues together with a mobile structural element composing the catalytic Cys190
      form a substrate-binding pocket that secludes the bound preQ0 completely from
      solvent. We show here that residue substitutions (E89A, E89L, and F228A) targeted
      at opening up the binding pocket weakened preQ0 binding at the preadduct stage by
      up to +10 kJ/mol and profoundly affected catalysis. Unlike wildtype enzyme, the
      QueF variants, including L191A and I192A, were no longer selective for preQ1
      formation. The E89A, E89L, and F228A variants performed primarily (>=90%) a two
      electron reduction of preQ0, releasing hydrolyzed imine (7-formyl-7-deazaguanine)
      as the product. The preQ0 reduction by L191A and I192A gave preQ1 and 7-formyl-7
      deazaguanine at a 4:1 and 1:1 ratio, respectively. The proportion of 7-formyl-7
      deazaguanine in total product increased with increasing substrate concentration,
      suggesting a role for preQ0 in a competitor-induced release of the imine
      intermediate. Collectively, these results provide direct evidence for the
      intermediacy of an imine in the QueF-catalyzed reaction. They reveal determinants
      of QueF structure required for imine sequestration and hence for a complete
      nitrile-to-amine conversion by this class of enzymes.

PMID- 29339557
TI  - Chronic dietary creatine enhances hippocampal-dependent spatial memory,
      bioenergetics, and levels of plasticity-related proteins associated with NF
      kappaB.
AB  - The brain has a high demand for energy, of which creatine (Cr) is an important
      regulator. Studies document neurocognitive benefits of oral Cr in mammals, yet
      little is known regarding their physiological basis. This study investigated the
      effects of Cr supplementation (3%, w/w) on hippocampal function in male C57BL/6
      mice, including spatial learning and memory in the Morris water maze and oxygen
      consumption rates from isolated mitochondria in real time. Levels of
      transcription factors and related proteins (CREB, Egr1, and IkappaB to indicate
      NF-kappaB activity), proteins implicated in cognition (CaMKII, PSD-95, and Egr2),
      and mitochondrial proteins (electron transport chain Complex I, mitochondrial
      fission protein Drp1) were probed with Western blotting. Dietary Cr decreased
      escape latency/time to locate the platform (P < 0.05) and increased the time
      spent in the target quadrant (P < 0.01) in the Morris water maze. This was
      accompanied by increased coupled respiration (P < 0.05) in isolated hippocampal
      mitochondria. Protein levels of CaMKII, PSD-95, and Complex 1 were increased in
      Cr-fed mice, whereas IkappaB was decreased. These data demonstrate that dietary
      supplementation with Cr can improve learning, memory, and mitochondrial function
      and have important implications for the treatment of diseases affecting memory
      and energy homeostasis.

PMID- 29339558
TI  - Does sleep facilitate the consolidation of allocentric or egocentric
      representations of implicitly learned visual-motor sequence learning?
AB  - Sleep facilitates the consolidation (i.e., enhancement) of simple, explicit
      (i.e., conscious) motor sequence learning (MSL). MSL can be dissociated into
      egocentric (i.e., motor) or allocentric (i.e., spatial) frames of reference. The
      consolidation of the allocentric memory representation is sleep-dependent,
      whereas the egocentric consolidation process is independent of sleep or wake for
      explicit MSL. However, it remains unclear the extent to which sleep contributes
      to the consolidation of implicit (i.e., unconscious) MSL, nor is it known what
      aspects of the memory representation (egocentric, allocentric) are consolidated
      by sleep. Here, we investigated the extent to which sleep is involved in
      consolidating implicit MSL, specifically, whether the egocentric or the
      allocentric cognitive representations of a learned sequence are enhanced by
      sleep, and whether these changes support the development of explicit sequence
      knowledge across sleep but not wake. Our results indicate that egocentric and
      allocentric representations can be behaviorally dissociated for implicit MSL.
      Neither representation was preferentially enhanced across sleep nor were
      developments of explicit awareness observed. However, after a 1-wk interval
      performance enhancement was observed in the egocentric representation. Taken
      together, these results suggest that like explicit MSL, implicit MSL has
      dissociable allocentric and egocentric representations, but unlike explicit
      sequence learning, implicit egocentric and allocentric memory consolidation is
      independent of sleep, and the time-course of consolidation differs significantly.

PMID- 29339559
TI  - Evidence of structure and persistence in motivational attraction to serial
      Pavlovian cues.
AB  - Sign-tracking is a form of autoshaping where animals develop conditioned
      responding directed toward stimuli predictive of an outcome even though the
      outcome is not contingent on the animal's behavior. Sign-tracking behaviors are
      thought to arise out of the attribution of incentive salience (i.e., motivational
      value) to reward-predictive cues. It is not known how incentive salience would be
      attributed to serially occurring cues, despite cues often occurring in a sequence
      in the real world as reward approaches. The experiments presented here
      demonstrate that reward-proximal cue responding is not altered by the presence of
      a distal reward cue (Experiment 1), and similarly that reward-distal cue
      responding which animals favor, is not altered by the presence of a reward
      proximal cue (Experiment 2). Extinction of reward-proximal cues after training of
      the serial sequence leads to a generalized reduction in lever responding
      (Experiment 3). Together, we show that both Pavlovian serial lever cues acquire
      motivational value. These experiments also provide support to the notion that
      sign-tracking responses are insensitive to changes in outcome value, and that
      responding to serial cues creates a distinct context for outcome value.

PMID- 29339560
TI  - Molecular correlates of separate components of training that contribute to long
      term memory formation after learning that food is inedible in Aplysia.
AB  - Training Aplysia with inedible food for a period that is too brief to produce
      long-term memory becomes effective in producing memory when training is paired
      with a nitric oxide (NO) donor. Lip stimulation for the same period of time
      paired with an NO donor is ineffective. Using qPCR, we examined molecular
      correlates of brief training versus lip stimulation, of treatment with an NO
      donor versus saline, and of the combined stimuli producing long-term memory.
      Changes were examined in mRNA expression of Aplysia homologs of C/EBP, CREB1,
      CREB1alpha, CREB1beta, and CREB2, in both the buccal and cerebral ganglia
      controlling feeding. Both the brief training and the NO donor increased
      expression of C/EBP, CREB1, CREB1alpha, and CREB1beta, but not CREB2 in the
      buccal ganglia. For CREB1alpha, there was a significant interaction between the
      effects of the brief training and of the NO donor. In addition, the NO donor, but
      not brief training, increased expression of all of the genes in the cerebral
      ganglion. These findings show that the components of learning that alone do not
      produce memory produce molecular changes in different ganglia. Thus, long-term
      memory is likely to arise by both additive and interactive increases in gene
      expression.

PMID- 29339561
TI  - Prepared stimuli enhance aversive learning without weakening the impact of verbal
      instructions.
AB  - Fear-relevant stimuli such as snakes and spiders are thought to capture attention
      due to evolutionary significance. Classical conditioning experiments indicate
      that these stimuli accelerate learning, while instructed extinction experiments
      suggest they may be less responsive to instructions. We manipulated stimulus type
      during instructed aversive reversal learning and used quantitative modeling to
      simultaneously test both hypotheses. Skin conductance reversed immediately upon
      instruction in both groups. However, fear-relevant stimuli enhanced dynamic
      learning, as measured by higher learning rates in participants conditioned with
      images of snakes and spiders. Results are consistent with findings that
      dissociable neural pathways underlie feedback-driven and instructed aversive
      learning.

PMID- 29339562
TI  - Sleep-dependent reductions in reality-monitoring errors arise from more
      conservative decision criteria.
AB  - Reality-monitoring errors occur when internally generated thoughts are remembered
      as external occurrences. We hypothesized that sleep-dependent memory
      consolidation could reduce them by strengthening connections between items and
      their contexts during an afternoon nap. Participants viewed words and imagined
      their referents. Pictures of the referents also accompanied half of the words.
      After a 2-h break filled with sleep (n = 31) or wakefulness (n = 32),
      participants indicated if they previously viewed a picture of each word. Nap
      participants made fewer reality-monitoring errors than wake participants by
      adopting more stringent response criteria, suggesting that sleep reduces reality
      monitoring errors primarily by influencing post-retrieval decision processes.

PMID- 29339563
TI  - The Diagnosis of UTI: Colony Count Criteria Revisited.

PMID- 29339564
TI  - Accuracy of the Urinalysis for Urinary Tract Infections in Febrile Infants 60
      Days and Younger.
AB  - OBJECTIVES: Reports of the test accuracy of the urinalysis for diagnosing urinary
      tract infections (UTIs) in young febrile infants have been variable. We evaluated
      the test characteristics of the urinalysis for diagnosing UTIs, with and without
      associated bacteremia, in young febrile infants. METHODS: We performed a planned
      secondary analysis of data from a prospective study of febrile infants <=60 days
      old at 26 emergency departments in the Pediatric Emergency Care Applied Research
      Network. We evaluated the test characteristics of the urinalysis for diagnosing
      UTIs, with and without associated bacteremia, by using 2 definitions of UTI:
      growth of >=50 000 or >=10 000 colony-forming units (CFUs) per mL of a
      uropathogen. We defined a positive urinalysis by the presence of any leukocyte
      esterase, nitrite, or pyuria (>5 white blood cells per high-power field).
      RESULTS: Of 4147 infants analyzed, 289 (7.0%) had UTIs with colony counts >=50
      000 CFUs/mL, including 27 (9.3%) with bacteremia. For these UTIs, a positive
      urinalysis exhibited sensitivities of 0.94 (95% confidence interval [CI]: 0.91
      0.97), regardless of bacteremia; 1.00 (95% CI: 0.87-1.00) with bacteremia; and
      0.94 (95% CI: 0.90-0.96) without bacteremia. Specificity was 0.91 (95% CI: 0.90
      0.91) in all groups. For UTIs with colony counts >=10 000 CFUs/mL, the
      sensitivity of the urinalysis was 0.87 (95% CI: 0.83-0.90), and specificity was
      0.91 (95% CI: 0.90-0.92). CONCLUSIONS: The urinalysis is highly sensitive and
      specific for diagnosing UTIs, especially with >=50 000 CFUs/mL, in febrile
      infants <=60 days old, and particularly for UTIs with associated bacteremia.

PMID- 29339566
TI  - Graphene Dirac point tuned by ferroelectric polarization field.
AB  - Graphene has received numerous attention for future nanoelectronics and
      optoelectronics. The Dirac point is a key parameter of graphene that provides
      information about its carrier properties. There are lots of methods to tune the
      Dirac point of graphene, such as chemical doping, impurities, defects, and
      disorder. In this study, we report a different approach to tune the Dirac point
      of graphene using a ferroelectric polarization field. The Dirac point can be
      adjusted to near the ferroelectric coercive voltage regardless its original
      position. We have ensured this phenomenon by temperature-dependent experiments,
      and analyzed its mechanism with the theory of impurity correlation in graphene.
      Additionally, with the modulation of ferroelectric polymer, the current on/off
      ratio and mobility of graphene transistor both have been improved. This work
      provides an effective method to tune the Dirac point of graphene, which can be
      readily used to configure functional devices such as p-n junctions and inverters.

PMID- 29339565
TI  - A Home Visiting Parenting Program and Child Obesity: A Randomized Trial.
AB  - BACKGROUND: Young children living in historically marginalized families are at
      risk for becoming adolescents with obesity and subsequently adults with increased
      obesity-related morbidities. These risks are particularly acute for Hispanic
      children. We hypothesized that the prevention-focused, socioecological approach
      of the "Minding the Baby" (MTB) home visiting program might decrease the rate of
      childhood overweight and obesity early in life. METHODS: This study is a
      prospective longitudinal cohort study in which we include data collected during 2
      phases of the MTB randomized controlled trial. First-time, young mothers who
      lived in medically underserved communities were invited to participate in the MTB
      program. Data were collected on demographics, maternal mental health, and
      anthropometrics of 158 children from birth to 2 years. RESULTS: More children in
      the intervention group had a healthy BMI at 2 years. The rate of obesity was
      significantly higher (P < .01) in the control group (19.7%) compared with the
      intervention group (3.3%) at this age. Among Hispanic families, children in the
      MTB intervention were less likely to have overweight or obesity (odds ratio =
      0.32; 95% confidence interval: 0.13-0.78). CONCLUSIONS: Using the MTB program, we
      significantly lowered the rate of obesity among 2-year-old children living in low
      socioeconomic-status communities. In addition, children of Hispanic mothers were
      less likely to have overweight or obesity at 2 years. Given the high and
      disproportionate national prevalence of Hispanic young children with overweight
      and obesity and the increased costs of obesity-related morbidities, these
      findings have important clinical, research, and policy implications.

PMID- 29339567
TI  - Erythrocyte membrane-coated gold nanocages for targeted photothermal and chemical
      cancer therapy.
AB  - Recently, red blood cell (RBC) membrane-coated nanoparticles have attracted much
      attention because of their excellent immune escapability; meanwhile, gold
      nanocages (AuNs) have been extensively used for cancer therapy due to their
      photothermal effect and drug delivery capability. The combination of the RBC
      membrane coating and AuNs may provide an effective approach for targeted cancer
      therapy. However, few reports have shown the utilization of combining these two
      technologies. Here, we design erythrocyte membrane-coated gold nanocages for
      targeted photothermal and chemical cancer therapy. First, anti-EpCam antibodies
      were used to modify the RBC membranes to target 4T1 cancer cells. Second, the
      antitumor drug paclitaxel (PTX) was encapsulated into AuNs. Then, the AuNs were
      coated with the modified RBC membranes. These new nanoparticles were termed EpCam
      RPAuNs. We characterized the capability of the EpCam-RPAuNs for selective tumor
      targeting via exposure to near-infrared irradiation. The experimental results
      demonstrate that EpCam-RPAuNs can effectively generate hyperthermia and precisely
      deliver the antitumor drug PTX to targeted cells. We also validated the
      biocompatibility of the EpCam-RAuNs in vitro. By combining the molecularly
      modified targeting RBC membrane and AuNs, our approach provides a new way to
      design biomimetic nanoparticles to enhance the surface functionality of
      nanoparticles. We believe that EpCam-RPAuNs can be potentially applied for cancer
      diagnoses and therapies.

PMID- 29339568
TI  - Bone surface enhancement in ultrasound images using a new Doppler-based
      acquisition/processing method.
AB  - Ultrasound (US) imaging has long been considered as a potential aid in orthopedic
      surgeries. US technologies are safe, portable and do not use radiations. This
      would make them a desirable tool for real-time assessment of fractures and to
      monitor fracture healing. However, image quality of US imaging methods in bone
      applications is limited by speckle, attenuation, shadow, multiple reflections and
      other imaging artifacts. While bone surfaces typically appear in US images as
      somewhat 'brighter' than soft tissue, they are often not easily distinguishable
      from the surrounding tissue. Therefore, US imaging methods aimed at segmenting
      bone surfaces need enhancement in image contrast prior to segmentation to improve
      the quality of the detected bone surface. In this paper, we present a novel
      acquisition/processing technique for bone surface enhancement in US images.
      Inspired by elastography and Doppler imaging methods, this technique takes
      advantage of the difference between the mechanical and acoustic properties of
      bones and those of soft tissues to make the bone surface more easily
      distinguishable in US images. The objective of this technique is to facilitate US
      based bone segmentation methods and improve the accuracy of their outcomes. The
      newly proposed technique is tested both in in vitro and in vivo experiments. The
      results of these preliminary experiments suggest that the use of the proposed
      technique has the potential to significantly enhance the detectability of bone
      surfaces in noisy ultrasound images.

PMID- 29339569
TI  - Experimental determination of configurational entropy in a two-dimensional liquid
      under random pinning.
AB  - A quasi two-dimensional colloidal suspension is studied under the influence of
      immobilisation (pinning) of a random fraction of its particles. We introduce a
      novel experimental method to perform random pinning and, with the support of
      numerical simulation, we find that increasing the pinning concentration smoothly
      arrests the system, with a cross-over from a regime of high mobility and high
      entropy to a regime of low mobility and low entropy. At the local level, we study
      fluctuations in area fraction and concentration of pins and map them to entropic
      structural signatures and local mobility, obtaining a measure for the local
      entropic fluctuations of the experimental system.

PMID- 29339570
TI  - Comparison of Monte Carlo and analytical dose computations for intensity
      modulated proton therapy.
AB  - To evaluate the effect of approximations in clinical analytical calculations
      performed by a treatment planning system (TPS) on dosimetric indices in intensity
      modulated proton therapy. TPS calculated dose distributions were compared with
      dose distributions as estimated by Monte Carlo (MC) simulations, calculated with
      the fast dose calculator (FDC) a system previously benchmarked to full MC. This
      study analyzed a total of 525 patients for four treatment sites (brain, head-and
      neck, thorax and prostate). Dosimetric indices (D02, D05, D20, D50, D95, D98, EUD
      and Mean Dose) and a gamma-index analysis were utilized to evaluate the
      differences. The gamma-index passing rates for a 3%/3 mm criterion for voxels
      with a dose larger than 10% of the maximum dose had a median larger than 98% for
      all sites. The median difference for all dosimetric indices for target volumes
      was less than 2% for all cases. However, differences for target volumes as large
      as 10% were found for 2% of the thoracic patients. For organs at risk (OARs), the
      median absolute dose difference was smaller than 2 Gy for all indices and
      cohorts. However, absolute dose differences as large as 10 Gy were found for some
      small volume organs in brain and head-and-neck patients. This analysis concludes
      that for a fraction of the patients studied, TPS may overestimate the dose in the
      target by as much as 10%, while for some OARs the dose could be underestimated by
      as much as 10 Gy. Monte Carlo dose calculations may be needed to ensure more
      accurate dose computations to improve target coverage and sparing of OARs in
      proton therapy.

PMID- 29339571
TI  - Infrared photoconductivity and photovoltaic response from nanoscale domains of
      PbS alloyed with thorium and oxygen.
AB  - Thin films of lead sulfide alloyed with thorium and oxygen were deposited on GaAs
      substrates and processed to produce a photo-diode structure. Structural, optical
      and electrical characterizations indicate the presence of small nanoscale domains
      (NDs) that are characterized by dense packaging, high quality interfaces and a
      blue-shift of the energy bandgap toward the short wavelength infrared range of
      the spectrum. Photocurrent spectroscopy revealed a considerable photoconductivity
      that is correlated with excitation of carriers in the NDs of lead sulfide alloyed
      with thorium and oxygen. Furthermore, the appearance of a photovoltaic effect
      under near infrared illumination indicates a quasi-type II band alignment at the
      interface of the GaAs and the film of NDs.

PMID- 29339572
TI  - Three-dimensional cross-linking composite of graphene, carbon nanotube and Si
      nanoparticles for lithium ion batteries anode.
AB  - Various graphene-based Si nanocomposites have been reported to improve the
      performance of active materials in &#13; Li ion battery. However, these
      candidates still yield severe capacity fading due to the electrical disconnection
      and &#13; fracture caused by huge volume changes with extended cycles.Therefore,
      we design a novel three-dimensional &#13; cross-linking structure of graphene and
      single-wall carbon nanotube to encapsulate Si nanoparticles. The &#13;
      synthesized three-dimensional structure is ascribed to the excellent self
      assembly of carbon nanotube with &#13; graphene oxide and a thermal treatment
      process at 900 oC. This special structure provides sufficient void spaces &#13;
      for volume expansion of Si nanoparticles and channels for the diffusion of ions
      and electrons, and the &#13; cross-linking of graphene and single wall carbon
      nanotube also strengthens the stability of structure. As a result, &#13; the
      volume expansion of Si nanoparticles is restrained. The specific capacity remains
      1450 mAh g-1 after 100 &#13; cycles at 200 mA g-1. This well-defined three
      dimensional structure facilitates superior capacity and cycling &#13; stability
      in comparison with bare Si and mechanically mixed composite electrode of
      graphene, single-wall &#13; carbon nanotube and silicon nanoparticles.

PMID- 29339573
TI  - 18F-choline PET/CT for parathyroid scintigraphy: significantly lower radiation
      exposure of patients in comparison to conventional nuclear medicine imaging
      approaches.
AB  - BACKGROUND: Parathyroid subtraction scintigraphy (PSS) is the most commonly used
      imaging method for localisation of hyperfunctioning parathyroid glands (HPGs) in
      primary hyperparathyroidism (PHP), a common endocrine disorder. Hybrid (SPECT/CT)
      imaging with 99mTc-sestaMIBI (MIBI) at an early and delayed phase (dual-phase
      imaging) may be the most accurate conventional imaging approach, but includes
      additional radiation exposure due to added CT imaging. Recently, 18F-choline
      (FCH) PET/CT was introduced for HPG imaging, which can also be performed using
      the dual-phase approach. To date, no studies have compared organ doses and the
      effective dose (ED) from conventional subtraction scintigraphy, dual-phase MIBI
      SPECT/CT, and FCH PET/CT in the localisation of HPGs. AIM: In addition to the
      comparison of the diagnostic performance of FCH PET/CT and conventional
      scintigraphic imaging methods, the aim of the study was to measure the organ
      doses and the ED for conventional subtraction parathyroid imaging protocols,
      using dual-phase MIBI SPECT/CT as a potential conventional imaging method of
      choice and FCH dual-phase PET/CT as a potential future imaging method of choice
      for the localisation of HPGs. Materials, methods. Thirty-six patients referred
      for parathyroid imaging with a clinical indication of PHP underwent preoperative
      PSS and dual-phase SPECT/CT imaging with the addition of FCH PET/CT. The
      diagnostic performance of the imaging modalities was assessed by using histology
      results as a gold standard. Radiation exposure was calculated for the
      administered activities of radiopharmaceuticals using ICRP80 weighting factors
      and for CT exposure at hybrid imaging using dose-length products and the ImPACT
      CT Patient Dosimetry Calculator. RESULTS: The diagnostic performance of FCH
      PET/CT was significantly better than that of conventional imaging modalities
      (sensitivity of 97% vs 64% and 46% for MIBI SPECT/CT and PSS, respectively, with
      comparable specificity of over 95% for all modalities). The highest radiation
      exposure was caused by conventional PSS (7.4 mSv), followed by dual-phase MIBI
      SPECT/CT (6.8 mSv). The radiation exposure was the lowest for dual-phase FCH
      PET/CT imaging (2.8 mSv). The added CT imaging for both hybrid approaches did not
      cause significant additional radiation exposure (1.4 mSv for MIBI SPECT/CT,
      additional 26.4% to overall exposure; 0.8 mSv for FCH PET/CT, additional 42.4% to
      overall exposure). CONCLUSION: In comparison to conventional scintigraphic
      imaging of HPGs, emerging hybrid (SPECT/CT, PET/CT) imaging techniques combine
      superior diagnostic performance with lower radiation exposure to patients.

PMID- 29339574
TI  - Phase diagram of carbon and the factors limiting the quantity and size of natural
      diamonds.
AB  - Phase diagrams of carbon, and those focusing on the graphite-to-diamond
      transitional conditions in particular, are of great interest for fundamental and
      applied research. The present study introduces a number of experiments carried
      out to convert graphite under high-pressure conditions, showing a formation of
      stable phase of fullerene-type onions cross-linked by sp3-bonds in the 55-115 GPa
      pressure range instead of diamonds formation (even at temperature 2000-3000 K)
      and the already formed diamonds turn into carbon onions. Our results refute the
      widespread idea that diamonds can form at any pressure from 2.2 to 1000 GPa. The
      phase diagram built within this study allows us not only to explain the existing
      numerous experimental data on the formation of diamond from graphite, but also to
      make assumptions about the conditions of its growth in Earth's crust.

PMID- 29339575
TI  - Dynamic PET image reconstruction integrating temporal regularization associated
      with respiratory motion correction for applications in oncology.
AB  - Respiratory motion reduces both the qualitative and quantitative accuracy of PET
      images in oncology. This impact is more significant for quantitative applications
      based on kinetic modeling, where dynamic acquisitions are associated with limited
      statistics due to the necessity of enhanced temporal resolution. The aim of this
      study is to address these drawbacks, by combining a respiratory motion correction
      approach with temporal regularization in a unique reconstruction algorithm for
      dynamic PET imaging. Elastic transformation parameters for the motion correction
      are estimated from the non-attenuation-corrected PET images. The derived
      displacement matrices are subsequently used in a list-mode based OSEM
      reconstruction algorithm integrating a temporal regularization between the 3D
      dynamic PET frames, based on temporal basis functions. These functions are
      simultaneously estimated at each iteration, along with their relative
      coefficients for each image voxel. Quantitative evaluation has been performed
      using dynamic FDG PET/CT acquisitions of lung cancer patients acquired on a GE
      DRX system. The performance of the proposed method is compared with that of a
      standard multi-frame OSEM reconstruction algorithm. The proposed method achieved
      substantial improvements in terms of noise reduction while accounting for loss of
      contrast due to respiratory motion. Results on simulated data showed that the
      proposed 4D algorithms led to bias reduction values up to 40% in both tumor and
      blood regions for similar standard deviation levels, in comparison with a
      standard 3D reconstruction. Patlak parameter estimations on reconstructed images
      with the proposed reconstruction methods resulted in 30% and 40% bias reduction
      in the tumor and lung region respectively for the Patlak slope, and a 30% bias
      reduction for the intercept in the tumor region (a similar Patlak intercept was
      achieved in the lung area). Incorporation of the respiratory motion correction
      using an elastic model along with a temporal regularization in the reconstruction
      process of the PET dynamic series led to substantial quantitative improvements
      and motion artifact reduction. Future work will include the integration of a
      linear FDG kinetic model, in order to directly reconstruct parametric images.

PMID- 29339576
TI  - A thermodynamics model for morphology prediction of aluminum nano crystals
      fabricated by the inert gas condensation method.
AB  - The purpose of this study is to provide scientific guidance for the morphological
      control of nanoparticle synthesis using the gas phase method. A universal
      thermodynamics model is developed to predict the morphology of nanoparticles
      fabricated using the inert gas condensation method. By using this model, the
      morphologies of aluminum nanocrystals are predicted under various preparation
      conditions. There are two types of energy that jointly determine the formation of
      nanoparticle morphology-Gibbs free energy for nanoparticles and energy variation
      during the process. The results show that energy variation dominates morphology
      formation when the cooling rate is less than 2 * 1011 K s-1 in the aluminum
      nanocrystal production process. At the beginning of the nanoparticle growth, the
      most stable morphology is predicted to be spherical, but the energetically
      preferred morphology becomes cubic as the particle grows. The turning point in
      the particle size at which spherical morphology is no longer the most stable
      morphology is exhibited as a function of pressure in a condensation chamber for
      different cooling rates. In this paper, we focus on the need for morphology
      prediction based on preparation conditions. It is concluded that nanoparticles
      with various morphologies could be obtained by adjusting the cooling rate and
      pressure in the condensation chamber.

PMID- 29339577
TI  - A wearable pressure sensor based on ultra-violet/ozone microstructured carbon
      nanotube/polydimethylsiloxane arrays for electronic skins.
AB  - Pressure sensors with high performance (e.g., a broad pressure sensing range,
      high sensitivities, rapid response/relaxation speeds, temperature-stable
      sensing), as well as a cost-effective and highly efficient fabrication method are
      highly desired for electronic skins. In this research, a high-performance
      pressure sensor based on microstructured carbon nanotube/polydimethylsiloxane
      arrays was fabricated using an ultra-violet/ozone (UV/O3) microengineering
      technique. The UV/O3 microengineering technique is controllable, cost-effective,
      and highly efficient since it is conducted at room temperature in an ambient
      environment. The pressure sensor offers a broad pressure sensing range (7 Pa-50
      kPa), a sensitivity of ~ -0.101 +/- 0.005 kPa-1 (<1 kPa), a fast
      response/relaxation speed of ~10 ms, a small dependence on temperature variation,
      and a good cycling stability (>5000 cycles), which is attributed to the UV/O3
      engineered microstructures that amplify and transfer external applied forces and
      rapidly store/release the energy during the PDMS deformation. The sensors
      developed show the capability to detect external forces and monitor human health
      conditions, promising for the potential applications in electronic skin.

PMID- 29339578
TI  - Functional metasurfaces based on metallic and dielectric subwavelength slits and
      stripes array.
AB  - Starting with the early works of extraordinary optical transmission and
      extraordinary Young's interference, researchers have been fascinated by the
      unusual optical properties displayed by metallic holes/slits and subsequently
      found similar abnormities in dielectric counterparts. Benefiting from the
      shrinking wavelength of surface plasmon polaritons excited in metallic slits and
      high refractive index of dielectric stripes, one can realize local phase
      modulation and approach desired dispersion by engineering the geometries of a
      slits and stripes array. In this review, we review recent developments in
      functional metasurfaces composed of various metallic and dielectric subwavelength
      slits and stripes arrays, with special emphasis on achromatic, ultra-broadband,
      quasi-continuous, multifunctional and reconfigurable metasurfaces. Particular
      attention is paid to provide insight into the design strategies for these
      devices. Finally, we give an outlook of the development in this fascinating area.

PMID- 29339579
TI  - Conclusions and recommendations from the 17th Workshop of the European ALARA
      Network 'ALARA in emergency exposure situations'.
AB  - The European ALARA Network regularly organises workshops on topical issues in
      radiation protection. In light of the Fukushima accident, the most recent
      workshop questioned the application of the ALARA principle in emergency exposure
      situations. This memorandum presents the conclusions and recommendations of this
      workshop. One of the outcomes is that the process of optimisation in emergency
      exposure situations should be flexible enough to be able to modify or refine
      decisions over the course of an accident. In the urgent phase, decisions must be
      made in a very time-constrained environment, based on scarce, uncertain and
      sometimes unreliable information. In this phase, optimisation and protection
      strategies are therefore developed and applied on the basis of conservative
      assumptions or 'reasonably foreseeable worst-case scenario' which could lead to
      an overestimation of the consequences. In the intermediate phase, knowledge of
      the situation improves, and more time is available to make the decision. This is
      reflected by adopting a less conservative approach, and transitioning to a more
      appropriate optimisation adapted as effectively as possible to the various
      exposure situations. When the situation is eventually stabilized (transition
      phase), there is time to shape the measures taken previously to reflect local
      conditions in the affected territories. In every phase, consideration should be
      given to the stakeholders, so that their needs and requirements can be
      incorporated as effectively as possible.

PMID- 29339580
TI  - Advantages of soft subdural implants for the delivery of electrochemical
      neuromodulation therapies to the spinal cord.
AB  - OBJECTIVE: We recently developed soft neural interfaces enabling the delivery of
      electrical and chemical stimulation to the spinal cord. These stimulations
      restored locomotion in animal models of paralysis. Soft interfaces can be placed
      either below or above the dura mater. Theoretically, the subdural location
      combines many advantages, including increased selectivity of electrical
      stimulation, lower stimulation thresholds, and targeted chemical stimulation
      through local drug delivery. However, these advantages have not been documented,
      nor have their functional impact been studied in silico or in a relevant animal
      model of neurological disorders using a multimodal neural interface. APPROACH: We
      characterized the recruitment properties of subdural interfaces using a realistic
      computational model of the rat spinal cord that included explicit representation
      of the spinal roots. We then validated and complemented computer simulations with
      electrophysiological experiments in rats. We additionally performed behavioral
      experiments in rats that received a lateral spinal cord hemisection and were
      implanted with a soft interface. MAIN RESULTS: In silico and in vivo experiments
      showed that the subdural location decreased stimulation thresholds compared to
      the epidural location while retaining high specificity. This feature reduces
      power consumption and risks of long-term damage in the tissues, thus increasing
      the clinical safety profile of this approach. The hemisection induced a transient
      paralysis of the leg ipsilateral to the injury. During this period, the delivery
      of electrical stimulation restricted to the injured side combined with local
      chemical modulation enabled coordinated locomotor movements of the paralyzed leg
      without affecting the non-impaired leg in all tested rats. Electrode properties
      remained stable over time, while anatomical examinations revealed excellent bio
      integration properties. SIGNIFICANCE: Soft neural interfaces inserted subdurally
      provide the opportunity to deliver electrical and chemical neuromodulation
      therapies using a single, bio-compatible and mechanically compliant device that
      effectively alleviates locomotor deficits after spinal cord injury.

PMID- 29339581
TI  - Strain-induced bi-thermoelectricity in tapered carbon nanotubes.
AB  - We show that carbon-based nanostructured materials are a novel testbed for
      controlling thermoelectricity and have the potential to underpin the development
      of new cost-effective environmentally-friendly thermoelectric materials. In
      single-molecule junctions, it is known that transport resonances associated with
      the discrete molecular levels play a key role in the thermoelectric performance,
      but such resonances have not been exploited in carbon nanotubes (CNTs). Here we
      study junctions formed from tapered CNTs and demonstrate that such structures
      possess transport resonances near the Fermi level, whose energetic location can
      be varied by applying strain, resulting in an ability to tune the sign of their
      Seebeck coefficient. These results reveal that tapered CNTs form a new class of
      bi-thermoelectric materials, exhibiting both positive and negative thermopower.
      This ability to change the sign of the Seebeck coefficient allows the
      thermovoltage in carbon-based thermoelectric devices to be boosted by placing
      CNTs with alternating-sign Seebeck coefficients in tandem.

PMID- 29339582
TI  - Oxidation of copper nanowire based transparent electrodes in ambient conditions
      and their stabilization by encapsulation: application to transparent film
      heaters.
AB  - Whereas the integration of silver nanowires in functional devices has reached a
      fair level of maturity, the integration of copper nanowires still remains
      difficult, mainly due to the intrinsic instability of copper nanowires in ambient
      conditions. In this paper, copper nanowire based transparent electrodes with good
      performances (33 Omega sq-1 associated with 88% transparency) were obtained, and
      their degradation in different conditions was monitored, in particular by
      electrical measurements, transmission electron microscopy, x-ray photoelectron
      spectrometry and Auger electron spectroscopy. Several routes to stabilize the
      random networks of copper nanowires were evaluated. Encapsulation through
      laminated barrier film with optical clear adhesive and atmospheric pressure
      spatial atomic layer deposition were found to be efficient and were used for the
      fabrication of transparent film heaters.

PMID- 29339583
TI  - Echocolor Doppler morpho-functional study of the jugulo-subclavian confluence in
      chronic cerebro-spinal venous insufficiency and multiple sclerosis patients.
AB  - OBJECTIVES: The aim of this work is to measure the mean diameter of the
      confluence jugulo- subclavian, the impact of different types of jugular
      confluences and the correlation between the types of confluences and the Valsalva
      maneuver (jugular reflux) in subjects with Chronic Cerebro-Spinal Venous
      Insufficiency (CCSVI) and Multiple Sclerosis. METHOD: We investigated by Echo
      Color-Doppler (ECD) 103 subjects (67 F 36M) of mean age 45 +/- 12 years (a
      minimum of 22 to a maximum of 79 years, with a median of 44 and a modal value 42
      years), mean EDSS of 4.7 and average disease duration of 12 years. RESULTS: The
      103 right jugular veins investigated had an average diameter of 8.4 +/- 2.4 mm
      (minimum 4.0, maximum 14.9 mm; median 7.9; modal value 7.6 mm). Three form types
      were found: 56 cylindrical, 29 conical and 18 funnel. Valsalva maneuver was
      positive in 30 patients. The 103 left jugular investigated had an average
      diameter of 8.9 +/- 2.4 mm (minimum 2.8, maximum 14.4 mm; median of 8.8; modal
      value 8.7 mm). The form types were found: 42 cylindrical, 45 conical and 16
      funnel. Valsalva maneuver was positive in 30 patients. CONCLUSIONS: The mean
      diameter of the jugular veins was 8.7 mm. Internal jugular veins with cylindrical
      morphology have a diameter smaller than other forms; this difference is
      statistically significant. The different morphology of the jugular vein
      confluence does not increase the possibility of a reflux because the positive
      Valsalva maneuvers are not statistically significant when compared to the various
      types. KEY WORDS: CCSVI, EchoColorDoppler Map, Jugulo-Subclavian Confluence
      Diameter.

PMID- 29339584
TI  - Delayed diagnosis and treatment of high grade blunt pancreatic trauma. Case
      report and review of literature.
AB  - INTRODUCTION: Despite technological advancement, high grade pancreatic injuries
      following blunt abdominal trauma continues to remain a disease that is associated
      with high morbidity and mortality rates, particularly in cases of delayed
      diagnosis. The aim of this paper was the presentation of delayed diagnosis and
      treatment peculiarities of high grade pancreatic trauma and a review of
      literature. CASE REPORT: A 55-years old man, involved in motor vehicle crashes,
      was referred to our level I trauma center. Hemodynamically stable. Abdominal
      physical exam, laboratory and focused abdominal sonography for trauma were
      normal. First total body multidetector CT scan, performed only after 24 hours,
      showed almost complete left pneumothorax, left third to fifth rib fractures and
      subcutaneous emphysema. Left chest tube was applied. On the eighth post-traumatic
      day, the general condition of the patient started to deteriorate. The patient
      showed abdominal pain, fever, nausea, vomiting, and bilateral flank ecchymosis.
      Only the third CT scan performed, on twelfth day, after the peritoneal signs,
      changes in blood and biochemical parameters appear, we revealed linear laceration
      and hypo-attenuation area of the neck and a part of distal body pancreas. In
      laparotomy fat necrosis, giant retroperitoneal abscess, necrosis of the neck and
      distal body of the pancreas, was found. Distal pancreatectomy with splenectomy
      was performed. Postoperative course with extensive wound infection and necrotic
      leakage from peripancreatic drain was complicated. The patient was discharged two
      months after his operation without any events. CONCLUSION: On time diagnosis of
      pancreatic trauma, especially in polytrauma patients, continues to remain a
      challenge for trauma surgeons. Main pancreatic duct injury is an important
      prognostic factor and the major one determining therapeutic approaches. Adequate
      surgical approaches decrease morbidity and mortality in pancreatic trauma. KEY
      WORDS: Delayed diagnosis, Distal pancreatectomy, Pancreatic blunt trauma.

PMID- 29339585
TI  - Can ultrasonic surgical devices be used to close the appendicular stump?
AB  - : Laparoscopic appendectomy is increasingly being performed because of its quick
      recovery time, low instance of wound infection, and early return of patients to
      home and work. Operating time should be short yet safe. Therefore, in this study,
      we compared the effects of various sealing systems on the length of surgery and
      examined whether these systems could be used to separate the appendix from its
      stump successfully. This prospective and randomized ex vivo study was conducted
      on 20 consecutive patients diagnosed with acute appendicitis. All patients
      underwent classical open appendectomy. The patients were classified into two
      groups according to the type of sealing system used. The LigaSure(r) system was
      used for coagulation in Group L and the Harmonic(r) system in Group H. After
      coagulation, a pressure system was used to evaluate the closure of the appendix.
      Results showed that the use of ultrasonic instruments alone to close the
      appendiceal stump caused an incomplete closure. KEY WORDS: Appendicular stump,
      Laparoscopic appendectomy.

PMID- 29339586
TI  - Validation of COLA score for predicting wound infection in patients undergoing
      surgery for rectal cancer.
AB  - AIM: The purpose of our study was to estimate the incidence of SSI (Surgical site
      infection) and the effect of COLA (contamination, obesity, laparotomy and ASA
      grade) score on SSI in patients undergoing rectal surgical procedures for rectal
      cancer. MATERIAL OF STUDY: A total of 92 patients who underwent operation for
      rectum cancer were enrolled in this study. Wound surveillance was performed in
      all patients by a staff surgeon identified infected wounds during the hospital
      stay, and collected information for up to 30 days after operation. RESULTS: The
      overall rate of incisional SSI and organ/space SSI was 22.8% and 7.6%
      respectively. Surgical site infection rates were 14.2%, 20.58%, 40.7%, 57.1% for
      COLA 1,2,3 and 4 scores respectively. The area under the receiver/ operator
      characteristic curve for the score was 0,660. CONCLUSION: COLA scoring systems
      predict, with reasonable accuracy, the risk of SSI in rectal cancer patients
      undergoing elective rectal surgery. KEY WORDS: COLA score Rectal surgery,
      Surgical site infection, Risk prediction, Wound infection.

PMID- 29339587
TI  - Microscopically positive (R1) resections do not affect survival in pancreatic
      head cancer.
AB  - BACKGROUND: Obtaining negative microscopic resection margins (R0) in cephalic
      duodenopancreatectomy (CDP) is the gold standard. Resection line involvement at
      microscopic histopathological examination (R1) could change prognostic
      unfavorable. Regarding R1 resections in CDP (data from the literature show rates
      between 20-80%), we considered it necessary to perform a study in Regional
      Institute of Gastroenterology and Hepatology "Prof. Dr. O. Fodor'' Cluj-Napoca.
      METHODS: Here we present the results of a retrospective study carried out between
      January 2012 - December 2013 in our Institute. This study includes 63 patients
      with pancreatic head resections for pancreatic cancer. The circumferential soft
      tissue margin, the pancreatic transection margin, the bile duct and
      duodenum/stomach margins were analyzed. We investigated the incidence of R1 and
      its impact on the survival rates after oncologic pancreatic resections using a
      nonstandardized pathologic routine protocol. R1 status was defined as the
      distance of the tumor from the resection margin of <= 1 mm. RESULTS: Pancreatic
      ductal adenocarcinoma (PDAC) was diagnosed in 93.65 %. The R1 rate was 36.5 % (23
      cases). The circumferential margins were most commonly involved as R1 (91,3%). No
      statistically significant differences were found between patients with R1 to
      those with R0 (p >= 0.1) regarding 3-year survival. CONCLUSIONS: Survival for
      pancreatic head cancer at 3 years is not influenced by the margins of resection
      (R1/R0). Microscopic resection margin involvement is not an independent marker of
      survival. KEY WORDS: Circumferential margins, Nonstandardized pathologic
      protocol, Pancreatic ductal adenocarcinoma, Positive margins R1 Survival.

PMID- 29339588
TI  - Recurrent residual or progressive varicose veins: postoperative long term follow
      up of 353 patients.
AB  - AIM: This study aimed to evaluate the postoperative incidence of recurrent
      varicose veins (vv) and the possibility to differentiate the different types of
      recurrence. MATERIAL OF STUDY: Patients who underwent surgery for saphenofemoral
      junction (SFJ) incompetence, great saphenous vein (GSV) varicosity and at least
      one perforator incompetence and varicosity of tributaries between January 1998
      and December 2003 were selected for the study. Surgery consisted in SFJ flush
      ligation, GSV stripping, perforator vein ligature, and phlebectomies. Patients
      were assessed by detailed interview, clinical examination, and color duplex
      imaging after 10 years. The differentiation in recurrent, residual and
      progressive vv was done by comparison of the pre-and intraoperative and the
      phlebographic documentation in particular with the findings on follow-up..
      RESULTS: 353 patients (400 legs) were analyzed at 120 +/- 21 months. At follow up
      the vv were classified as recurrent in 23,75%, residual in 23,25%, and
      progressive in 21% of cases. Nine patients (1.9%) were reoperated after 70 +/- 33
      months, and 17 (3.5%) underwent sclerotherapy during follow-up. CONCLUSIONS:
      Recurrent, residual, and progressive vv can be clearly differentiated with the
      presented methodology. The authors suggest a revised definition (NEVVAS- new vv
      after surgery) because the term recurrent and the known acronyms do not embrace
      exactly the three types of vv after surgery. Since residual and many recurrent vv
      are due to avoidable technical or tactical errors, it is important to classify
      them properly in order to avoid these complications. KEY WORDS: Neovarices,
      NEVVAS (New Varicose Veins After Surgery), Neovascularization, Recurrent varicose
      veins, Residual varicose veins, Progressive varicose veins.

PMID- 29339589
TI  - Patient-perceived outcomes of different anaesthetic techniques in classical
      surgical treatment of varicose veins of lower limbs.
AB  - AIM OF THE STUDY: To evaluate the effects of spinal or locoregional anaesthesia
      versus local tumescent anesthesia during traditional surgical treatment of
      saphenous reflux, in terms of pain and postoperative functional recovery.
      MATERIALS AND METHODS: From January to December 2014, 195 consecutive
      interventions of stripping of the greater saphenous vein for valvular
      incompetence were performed. In 114 cases spinal or locoregional anaesthesia was
      performed (group 1), in the remaining 81 cases local anaesthesia with the
      tumescence technique was carried out (group 2). All patients underwent an
      assessment of perceived pain by means of verbal rating scale before and at the
      end of surgery, at discharge and after a month. The times of recovery of
      ambulation during hospital stay and at the discharge were recorded and use of
      analgesic drugs during hospitalization and at home. At the end of the study,
      patients were asked to express their approval rating on the type of anaesthesia.
      RESULTS: Patients in group 2 experienced mild to moderate intraoperative pain
      more frequently than patients in group 1 (p<0.001), while patients in group 1 had
      more mild adverse anaesthesia-related events than patients in group 2. Patients
      in group 2 had faster recovery of ambulation and earlier discharge than patients
      in group 1.Thirty-day results were similar in the two groups; however, patients
      in group 2 had a higher degree of satisfaction than patients in group 1 with
      regard to the type of anaesthesia (p<0.001) CONCLUSIONS: Both locoregional and
      local tumescent anaesthesia are effective and well accepted by the patients, with
      similar intra-hospital and 30-day results. KEY WORDS: Great Saphenous Vein, Local
      tumescent anaesthesia, Pain, Stripping.

PMID- 29339590
TI  - Rectal cancer: factors predicting short outcomes after radical anterior
      resection.
AB  - AIM: This study analyzes risk factors implicated in postoperative complications
      and mortality after anterior resection in rectal cancer. MATERIAL AND METHODS: A
      total number of 378 patients with anterior rectal resection, diagnosed with
      rectal cancer and admitted at the IIIrd Surgery Clinic, "Octavian Fodor" Regional
      Institute of Gastroenterology and Hepatology, Romania, between 2009 and 2016. The
      inclusion criteria were anterior rectal resections with curative visa for rectal
      cancer. The complications we assessed are the following: anastomotic fistula,
      intra-abdominal infections, postoperative bowel obstruction and wound infection.
      RESULTS: There was statistical significance regarding male gender, emergency
      hospitalization, hypoproteinemia and the resumption of intestinal transit.
      Anterior rectal resection of tumors located on the middle rectum was associated
      with high rate of anastomotic fistula. Patients with manual suture of anastomosis
      developed intraabdominal abscess more frequently. In the multivariate analysis,
      hypoproteinemia and a number of lymph nodes >1 remained independently associated
      with the occurrence of wound infection. The 30-day mortality rate was 4.8% with
      18 deaths and morbidity rate 20.6% with 78 cases. CONCLUSIONS: Major
      complications after radical resection for rectal cancer are dependent on multiple
      variables such as male patients, those admitted in emergency and patients with
      hypoproteinemia. Location of tumor on middle rectum, manual suture of
      anastomosis, number of lymph nodes > 1 were associated with high rate of
      morbidity. Patients with coronary heart disease and diabetes mellitus didn't had
      statistical significance, but the rate of morbidity and mortality remains high in
      this groups. KEY WORDS: Complications, Radical anterior resection, Rectal cancer,
      Risk factors.

PMID- 29339591
TI  - Perineural infiltration as a prognostic factor in surgically treated gallbladder
      cancer A single center experience and literature review.
AB  - INTRODUCTION: Gallbladder cancer (GBC) is the most incident cancer of the biliary
      tract with only 5-13% of the sufferers surviving for five years. The aim of this
      study was to evaluate the prognostic role of perineural invasion (PNI) and its
      association with several clinicopathological variables in a cohort of surgically
      treated patients, and through a comprehensive review of the scientific
      literature. MATERIALS AND METHODS: Twenty-five consecutive patients submitted to
      curative surgery for GBC from 2008 through 2016 were enrolled. Demographic,
      clinical and pathological data were retrieved from medical files, and specimens
      were re-examined by two experienced pathologists. The Pubmed database was
      searched for articles reporting on perineural infiltration on gallbladder cancer.
      RESULTS: Perineural invasion was observed in 14 (56%) cases, and it was more
      frequent in higher pathological stages. A statistically significant association
      was found with high preoperative serum Ca 19-9 levels. Fourteen (56%) patients
      died during the follow-up; survival was lower in patients with perineural
      invasion in comparison to those without, but not statistically significant.
      Twelve English-language articles reporting on PNI were retrieved and discussed.
      CONCLUSIONS: Perineural invasion is associated with higher stage and poorer
      survival in surgically treated GBC patients. In patients with locally advanced
      GBC resection of the extrahepatic biliary duct and frozen section examination of
      the distal stump must be taken into consideration, especially in cases of tumor
      arising from the hepatic side of the gallbladder. In cases without residual
      disease but with pathological evidence of PNI, a careful follow-up is suggested
      to early detect recurrences. KEY WORDS: Adenocarcinoma, Cancer, Gallbladder,
      Perineural infiltration, Surgery.

PMID- 29339592
TI  - Day surgery in Romania.
AB  - AIM: Well know in USA, Australia and then in western European countries, day
      surgery is still at the beginning in Romania and eastern European countries. In
      this paper we want to analyze the evolution and actual situation of day surgery
      in Romania and in County Emergency Hospital Timisoara (CEHT). MATERIAL AND
      METHODS: In the implementation of day surgery in our country there were two
      distinct periods. Between 2007- 2013 the CEHT negotiated its own day surgery
      baskets with Local Health Insurance Company (LHIC). Starting from 2014 until now,
      the National Health Insurance Company has established new day surgery baskets
      which can be negotiated between CEHT and LHIC. RESULTS: Our study shows that day
      surgery in CEHT has had an undulating evolution - after a rising development at
      the beginning it stopped for a few years and now it has an ascendant evolution.
      DISCUSSION: In this context, International Association for Ambulatory Surgery
      (IAAS) has initiated a series of actions to support implementation and
      development of day surgery in Romania and Eastern European countries. The first
      action was the support that the International Association for Ambulatory Surgery
      gave to the Romanian Society of Ambulatory Surgery in organizing on 15-16
      September 2013 in Timisoara the course "Day Surgery - Making it Happen Overcoming
      Obstacles and Barriers". Discussions after the presentation of local realities in
      Eastern and Western Europe were particularly creative, being the stand in the
      accelerated development of day surgery in Romania. CONCLUSIONS: Day surgery and
      ambulatory surgery have many advantages for patients (increased comfort, lower
      surgical risk, minimal stress and low anxiety, high satisfaction rate), for
      hospital (reducing congestion in hospital, enabling it to have a better capacity
      to deal with serious cases), and for healthcare (increased economic efficiency,
      cost / patient / surgery is lower than for continuous admissions). Known in our
      country from 2000, the implementation of day surgery still faces many hardships.
      KEY WORDS: Day surgery, ambulatory surgery, Short hospitalization.

PMID- 29339593
TI  - The prognostic role of tumor size in patients with gastric cancer.
AB  - AIM: The identification of prognostic factors in gastric cancer is important for
      predicting patients' survival and determining therapeutic strategies. MATERIALS
      OF STUDY: A retrospective analysis ofpatients who underwent surgery for gastric
      cancer between 1996 and 2010. The appropriate cut-off value of tumor size related
      to survival was determined using receiver-operating characteristic (ROC) curves
      and it was 2,5 cm. Patients were divided into three groups: a small size group
      (SSG, < 2,5 cm), a medium size group (MSG, between 2,5 and 5 cm) and a large size
      group (LSG, >= 5 cm). RESULTS: Depth of invasion and lymph node metastasis
      resulted significantly related to tumor size (p < 0.05). Kaplan- Meier survival
      curves showed that OS rate was significantly higher in SSG patients. The
      prognosis of patients with tumor size < 2,5 cm was better than patients with
      tumors >= 2.5 cm in size (p < 0.01). DISCUSSION: The tumor size resulted
      significantly related to OS and it was related to depth of invasion and lymph
      node metastasis that are themselves prognostic factors. These results confirm and
      reinforced literature and suggest that at diagnostic pre-operative work-up we can
      yet define a prognostic value based on tumor size and underline the primary role
      of complete resection with free surgical margins and D2 lymphadenectomy.
      CONCLUSION: In patients with gastric cancer tumor size suggests information about
      the malignancy of the tumor: it is an important predictor of survival and 2,5 cm
      may be considered as a valid cut-off to define a better or worse prognosis. KEY
      WORDS: Gastric cancer, Prognosis,Survival, Tumor size.

PMID- 29339594
TI  - The effects of Crenotherapy and exercise in peripheral arterial occlusive
      disease. A comparison with simple exercise training.
AB  - BACKGROUND: Conservative therapies for patients affected by Peripheral Arterial
      Occlusive Disease (PAOD) aim first to correct the risk factors and to slow down
      the disease progression. Among these, exercise has positive effects on blood
      flow, muscle metabolism and well demonstrated systemic effects. These include
      reduction of chronic inflammation markers, improvement of walking mechanics and
      heart function. Controlled physical training increases the ability to perform the
      daily activities improving life expectancy of these patients. The aim of this
      study is to evaluate the effects and the effectiveness of physical training
      performed in thermal water compared to traditional treadmill walking exercise.
      METHODS: 98 patients affected by IIb stage PAOD, according to Leriche-Fontaine
      classification, were enrolled. Patients were randomized into two groups: the
      first arm carried out an intensive training program under medical supervision
      (group A); the second one carried out a rehabilitative exercise associated with
      crenotherapy (group B). The following parameters were detected: Ankle-Brachial
      pressure index (ABI), actual claudication distance (ACD), maximum walking
      distance (MWD), flow mediated dilatation (FMD) and the intima-media thickness
      (IMT). All patients underwent Doppler echocardiography and complete biochemical
      assay. RESULTS: In both groups, there was a statistically significant improvement
      of lipidaemia compared to baseline. When compared with each other, the two groups
      did not show statistically significant differences. There were no significant
      differences between the two groups regarding echocardiographic findings. Vascular
      reactivity study showed a statistically significant improvement of FMD after 3
      months of exercise in both groups. In crenotherapy group (B) FMD values were
      significantly higher than the treadmill ones (A). In both groups a statistically
      significant improvement in ACD was observed CONCLUSIONS: Our experience shows
      that crenotherapy has similar effects compared to traditional physical training
      in the treatment of PAOD, being equally well tolerated and safe; it gives an
      advantage over conventional physical training in terms of ACD and MWD
      improvement, although not statistically significant, and it is extremely welcome
      to patients compared to traditional physical training. KEY WORDS:
      Arterioscleroses, Intermittent Claudicatio, Peripheral Arterial Diseasen,
      Physical Exercise, Rehabilitation.

PMID- 29339595
TI  - Surgical outcomes in patients with hepatic synchronous and metachronous
      colorectal metastases.
AB  - AIM: To evaluate the impact of several clinical and pathological factors on the
      outcomes of surgery for hepatic colorectal cancer metastasis. METHODS: Eighty
      four liver metastasectomies in 77 consecutive patients with 90 colorectal cancer
      hepatic metastases were performed in our institution from 2009 to 2014. Surgery
      was carried out in 75 cases, as two patients were not eligible for surgery. Among
      them 43 (Group A) were affected by synchronous, and 32 (Group B) by metachronous
      lesions. Furthermore, 9 reoperations were performed in patients with initially
      synchronous lesions. The follow-up after surgery included total body CT scan
      every 3 months for the first year, and every 6 months for 4 years thereafter.
      Blood level of CEA was determined every 3 months. RESULTS: The univariate
      analysis evidenced significantly more recurrences in patients with synchronous
      lesions (p=0.011), and higher grade, pN stage and CEA blood levels. In
      multivariate logistic regression analysis the statistically significant
      parameters found were: the pT stage (OR: 3.92, p = 0.039), the use of adjuvant
      chemotherapy for the colonic tumor (OR: 0.19, p = 0.025), and the adjuvant
      chemotherapy (OR: 4.11, p = 0.048). The global survival was 32 patients (41.5%),
      17 with synchronous and 15 with metachronous lesions, and a significant
      difference in long-term survival between these two groups was found (p = 0.008).
      CONCLUSIONS: The most relevant prognostic factor in patients with hepatic
      colorectal cancer dissemination is the timing of metastasis; the metachronous
      lesions present better survival when surgically treated. KEY WORDS: Colorectal
      cancer, Liver, Metastasis, Surgery.

PMID- 29339596
TI  - Is ultrasound a reliable diagnostic tool for acute appendicitis? A single centre
      experience.
AB  - AIM: Aim of the present study is to evaluate the utility of US as a diagnostic
      method for acute appendicitis (AA) in a district general hospital, by use of
      accurate quality indices. MATERIAL AND METHODS: The records of all patients who
      underwent an appendicectomy in a one year period in a single centre were
      reviewed. The patients who underwent a preoperative US scan were included in the
      study in accordance to specific criteria and the results were statistically
      compared to the final surgical histology. RESULTS: 137 patients who underwent an
      US were included in the study, with 69 patients (23%) presenting a negative
      histology result. Overall, the US results correlated statistically significantly
      with the final histology results, with a specificity of 0.87, a sensitivity of
      0.34 and an overall diagnostic accuracy of 0.51. DISCUSSION: The results of the
      study are comparable with the reported literature, presenting high specificity
      but a relatively low sensitivity, although great variability exists in the
      literature. US seems useful in confirming rather than excluding AA. CONCLUSION:
      In view of its advantages, the incorporation of ultrasonography into routine
      clinical practice when performed by an expert is recommended, but only in support
      of other diagnostic elements. The issue of low sensitivity should be further
      addressed. KEY WORDS: Appendicectomy, Diagnostic accuracy, Histology.

PMID- 29339597
TI  - Unexpected findings in the routine histopathological examinations of appendectomy
      specimens A retrospective analysis of 1,970 patients.
AB  - INTRODUCTION: 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. METHODS: The files of 1,970 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 post-operation follow-ups were recorded. RESULTS: 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. CONCLUSION:
      Although all of the appendectomy samples were normal macroscopically, data from
      this study suggest that all specimens should be sent for routine investigation.
      KEY WORDS: Appendicitis, Appendectomy, Carcinoid, Mucocele, Endometriosis.

PMID- 29339598
TI  - Design parameter estimations for adjustable bubble size in bubble generating
      system.
AB  - In this study, we developed a customized low cost and low energy bubble generator
      that can control bubble size. Hence, it can be used not only in the water
      treatment process but also in various other processes. This device was able to
      generate bubbles with a very simple system using only a general pump and a mixing
      chamber. Increasing the number of partition walls in the mixing chamber reduced
      the bubble size. Furthermore, bubbles of a few hundred nanometers were produced
      by the shear stress caused by increasing the thickness of the partition wall.
      Although the generated sub-micron bubbles were too small for their exact size to
      be measured using an image analysis and particle counting method, it was possible
      to confirm their existence indirectly through the coalescence arising from
      ultrasonic irradiation. The device used in this research is simple and allows
      bubble size to be adjusted easily by controlling the design of the mixing
      chamber. Therefore, it can be applied to a water treatment process, as well as a
      variety of other processes.

PMID- 29339599
TI  - Full-scale performance of selected starch-based biodegradable polymers in sludge
      dewatering and recommendation for applications.
AB  - Agricultural reuse of dewatered sludge is a valid route for sludge valorization
      for small and mid-size wastewater treatment plants (WWTPs) due to the direct
      utilization of nutrients. A more stringent of German fertilizer ordinance
      requires the degradation of 20% of the synthetic additives like polymeric
      substance within two years, which came into force on 1 January 2017. This study
      assessed the use of starch-based polymers for full-scale dewatering of municipal
      sewage sludge. The laboratory-scale and pilot-scale trials paved the way for full
      scale trials at three WWTPs in Germany. The general feasibility of applying
      starch-based 'green' polymers in full-scale centrifugation was demonstrated.
      Depending on the sludge type and the process used, the substitution potential was
      up to 70%. Substitution of 20-30% of the polyacrylamide (PAM)-based polymer was
      shown to achieve similar total solids (TS) of the dewatered sludge. Optimization
      of operational parameters as well as machinery set up in WWTPs is recommended in
      order to improve the shear stability force of sludge flocs and to achieve higher
      substitution potential. This study suggests that starch-based biodegradable
      polymers have great potential as alternatives to synthetic polymers in sludge
      dewatering.

PMID- 29339600
TI  - Scaling up and kinetic model validation of Direct Black 22 degradation by
      immobilized Penicillium chrysogenum.
AB  - This research was undertaken to develop tools that facilitate the industrial
      application of an immobilized loofah-fungi system to degrade Direct Black 22
      (DB22) azo dye. In laboratory-scale tests, the DB22, and loofah as support, were
      used. Assays without loofah were used as a free-cells control. The use of natural
      carriers to facilitate adhesion and growth of the fungi has shown favorable
      results. The degradation rate of immobilized cells increased twice as compared to
      free-cells control. At day 5 the decolorization was almost complete, while
      without loofah the total decolorization took more than 10 days. After 10 days,
      the extent of growth was nine times higher for the immobilized assays in
      comparison with the control flask. In subsequent experiments decolorization of
      DB22 was proven in a bench-scale reactor. A previously developed kinetic model
      was validated during the process. The model validation over free-cells assays
      gives an average normalized root mean squared error (ANRMSE) of 0.1659.
      Recalibration steps allowed prediction of the degradation with immobilized cells,
      resulting in an ANRMSE of 0.1891. A new calibration of the model during the
      scaling-up process yielded an ANRMSE of 0.1136 for DB22. The results presented
      encourage the use of this modeling tool in industrial scale facilities.

PMID- 29339601
TI  - Ammonium removal in landfill leachate using SBR technology: dispersed versus
      attached biomass.
AB  - Large concentrations and oscillations of ammonium nitrogen (NH4+-N) in municipal
      landfill leachate pose considerable constraints to its further treatment in
      central wastewater treatment plants. The aim of this study was to evaluate and
      optimize two technologies for the pre-treatment of 600 L/day of landfill
      leachate: in particular, to optimize their operational conditions for NH4+-N
      removal up to a level appropriate for discharge to sewers, i.e. <200 mg/L. Both
      technologies were based on a sequencing batch reactor (SBR), with two different
      biomass processes: (A) SBR with dispersed/flocculated biomass and (B) SBR with
      biomass attached to carriers. The results revealed that both technologies
      successfully reduced the NH4+-N from 666 mg/L (on average) at the inflow to below
      10 mg/L at the outflow with alkalinity adjustment in a 12-hour cycle. Both
      technologies achieved 96% removal efficiencies for NH4+-N. However, SBR with
      dispersed biomass showed higher flexibility under varying conditions due to the
      shorter adaptation time of the biomass.

PMID- 29339602
TI  - Performance and stability of an expanded granular sludge bed reactor modified
      with zeolite addition subjected to step increases of organic loading rate (OLR)
      and to organic shock load (OSL).
AB  - This paper shows the effect of organic shock loads (OSLs) on the anaerobic
      digestion (AD) of synthetic swine wastewater using an expanded granular sludge
      bed (EGSB) reactor modified with zeolite. Two reactors (R1 and R2), each with an
      effective volume of 3.04 L, were operated for 180 days at a controlled
      temperature of 30  degrees C and hydraulic retention time of 12 h. In the case of
      R2, 120 g of zeolite was added. The reactors were operated with an up-flow
      velocity of 6 m/h. The evolution of pH, total Kjeldahl nitrogen, chemical oxygen
      demand (COD) and volatile fatty acids (VFAs) was monitored during the AD process
      with OSL and increases in the organic loading rate (OLR). In addition, the
      microbial composition and changes in the structure of the bacterial and archaeal
      communities were assessed. The principal results demonstrate that the presence of
      zeolite in an EGSB reactor provides a more stable process at higher OLRs and
      after applying OSL, based on both COD and VFA accumulation, which presented with
      significant differences compared to the control. Denaturing gradient gel
      electrophoresis band profiles indicated differences in the populations of
      Bacteria and Archaea between the R1 and R2 reactors, attributed to the presence
      of zeolite.

PMID- 29339603
TI  - Simultaneous organic matter removal and nitrification of an inert self-supporting
      immersed media to upgrade aerated lagoons.
AB  - A pilot study was performed to evaluate the potential of an inert self-supported
      immersed fixed film media to upgrade aerated lagoons. Simultaneous organic matter
      removal and nitrification was assessed under different loading rates and
      temperatures (near 0  degrees C) using 12 laboratory-scale reactors operated in
      parallel. Test results showed that both the temperature and the load have an
      influence on organic matter effluent concentrations. Effluent quality seemed
      related to the observed biofilm thickness. Thicker biofilm is believed to have
      contributed to biomass detachment and increased particulate organic matter
      concentrations in the effluent. Simultaneous organic removal and nitrification
      was obtained at loads above 5 g CBOD5/m2.d. The highest nitrification rate at 0.4
      degrees C was obtained for the smallest load, which showed a nitrification
      limitation close to freezing point.

PMID- 29339604
TI  - Modeling biosorption of Cr(VI) onto Ulva compressa L. from aqueous solutions.
AB  - The marine biomass Ulva compressa L. (ECL) was used as a low-cost biosorbent for
      the removal of Cr(VI) from contaminated aqueous solutions. The operating
      variables were optimized: pH ~ 2, initial concentration of 25 mg/L, solid/liquid
      ratio of 6 g/L and a temperature of 50  degrees C, leading to an uptake
      elimination of 96%. A full factorial experimental design technique enabled us to
      obtain a mathematical model describing the Cr(VI) biosorption and to study the
      main effects and interactions among operational parameters. The equilibrium
      isotherm was analyzed by the Langmuir, Freundlich and Dubinin-Radushkevich (D-R)
      models; it has been found that the adsorption process follows well the Langmuir
      model. Kinetic studies showed that the pseudo-second order model describes
      suitably the experimental data. The thermodynamic parameters indicated an
      endothermic heat and a spontaneity of the Cr(VI) biosorption onto ECL.

PMID- 29339605
TI  - Enhancing nitrogen removal efficiency in a dyestuff wastewater treatment plant
      with the IFFAS process: the pilot-scale and full-scale studies.
AB  - The activated sludge (AS) process is widely applied in dyestuff wastewater
      treatment plants (WWTPs); however, the nitrogen removal efficiency is relatively
      low and the effluent does not meet the indirect discharge standards before being
      discharged into the industrial park's WWTP. Hence it is necessary to upgrade the
      WWTP with more advanced technologies. Moving bed biofilm processes with suspended
      carriers in an aerobic tank are promising methods due to enhanced nitrification
      and denitrification. Herein, a pilot-scale integrated free-floating biofilm and
      activated sludge (IFFAS) process was employed to investigate the feasibility of
      enhancing nitrogen removal efficiency at different hydraulic retention times
      (HRTs). The results showed that the effluent chemical oxygen demand (COD),
      ammonium nitrate (NH4+-N) and total nitrogen (TN) concentrations of the IFFAS
      process were significantly lower than those of the AS process, and could meet the
      indirect discharge standards. PCR-DGGE and FISH results indicated that more
      nitrifiers and denitrifiers co-existed in the IFFAS system, promoting
      simultaneous nitrification and denitrification. Based on the pilot results, the
      IFFAS process was used to upgrade the full-scale AS process, and the effluent
      COD, NH4+-N and TN of the IFFAS process were 91-291 mg/L, 10.6-28.7 mg/L and 18.9
      48.6 mg/L, stably meeting the indirect discharge standards and demonstrating the
      advantages of IFFAS in dyestuff wastewater treatment.

PMID- 29339606
TI  - Study of aggregation in surface sludge deposits from 14 full-scale French
      constructed wetlands using particle size distribution and dynamic vapor sorption
      analyses.
AB  - French vertical flow constructed wetlands (French VFCWs) are widely used for the
      treatment of wastewaters from small communities. In the system, unsettled
      wastewater is percolated through two successive stages of filter-cells planted
      with reeds. This causes the formation of a surface sludge layer. This layer plays
      positive roles in the treatment performance, but also leads to clogging. The
      objective of this study was to contribute to the description of the sludge
      deposits characteristics and their dynamics of evolution, which may control the
      development of clogging. Representative samples of sludge deposits were taken
      from 14 French VFCWs full-scale plants and analyzed for particle size, dynamic
      vapor sorption and other parameters of composition to compare their structure and
      evaluate the factors of influence. Results showed that ageing of the surface
      deposits layer over the years of operation in each plant induced the formation
      and integration of microaggregates within the initial macrostructure of fresh
      organic matter (OM). The humification process of the OM was found to play a key
      role in the aggregation process. The injection of FeCl3 operated to precipitate
      phosphates before filtration was found to accelerate the aggregation process in
      the early phase (<1 year) of operation of the sludge.

PMID- 29339607
TI  - Batch and fixed-bed column study for p-nitrophenol, methylene blue, and U(VI)
      removal by polyvinyl alcohol-graphene oxide macroporous hydrogel bead.
AB  - There is an increasing need to explore effective and clean approaches for
      hazardous contamination removal from wastewaters. In this work, a novel bead
      adsorbent, polyvinyl alcohol-graphene oxide (PVA-GO) macroporous hydrogel bead
      was prepared as filter media for p-nitrophenol (PNP), dye methylene blue (MB),
      and heavy metal U(VI) removal from aqueous solution. Batch and fixed-bed column
      experiments were carried out to evaluate the adsorption capacities of PNP, MB,
      and U(VI) on this bead. From batch experiments, the maximum adsorption capacities
      of PNP, MB, and U(VI) reached 347.87, 422.90, and 327.55 mg/g. From the fixed-bed
      column experiments, the adsorption capacities of PNP, MB, and U(VI) decreased
      with initial concentration increasing from 100 to 400 mg/L. The adsorption
      capacities of PNP, MB, and U(VI) decreased with increasing flow rate. Also, the
      maximum adsorption capacity of PNP decreased as pH increased from 3 to 9, while
      MB and U(VI) presented opposite tendencies. Furthermore, the bed depth service
      Time (BDST) model showed good linear relationships for the three ions' adsorption
      processes in this fixed-bed column, which indicated that the BDST model
      effectively evaluated and optimized the adsorption process of PVA-GO macroporous
      hydrogel bead in fixed-bed columns for hazardous contaminant removal from
      wastewaters.

PMID- 29339608
TI  - Pilot study of oilfield wastewater treatment by micro-flocculation filtration
      process.
AB  - In order to meet the latest Environmental Protection Law of China on wastewater
      discharge standards, this paper studied a pilot-scale micro-flocculation
      filtration pretreatment process for the treatment of oilfield wastewater. The
      experiment showed that the removal rate of oil and suspended solids (SS)
      respectively increased from 91.52% to 95.38% and from 66.42% to 97.19%. After the
      treatment by the micro-flocculation filtration device, the relevant
      characteristics of the discharge wastewater satisfied the latest standards
      continuously. Moreover, the polyaluminum chloride (PAC) dosage was reduced from
      200 mg/L to 100 mg/L (50 mg/L in micro-flocculation device and 50 mg/L in the
      cyclone reactor) at the same time. In order to decrease the degree of scaling in
      the filter, ceramsite was chosen as the filter material instead of quartz sand
      that is widely applied in the oilfields. The scaling experiment showed that the
      HCO3-, Ca2+ and Mg2+ contents in the extract from quartz sand after the scaling
      study were increased by 38.05, 35.91 and 0.28 mg/L, respectively. Meanwhile, the
      HCO3-, Ca2+ and Mg2+ contents in the extract from ceramsite were only increased
      by 13.14, 6.26 and 0.27 mg/L, respectively. Therefore, the ceramsite is not so
      prone to scaling as compared to quartz sand under identical test conditions,
      which avoided a hardened and impervious filter after operating for some time.
      These results suggest that the micro-flocculation filtration with the ceramsite
      as filter media is a suitable pretreatment process for the oilfield wastewater
      treatment.

PMID- 29339609
TI  - Effects of pH and coexisting chemicals on photolysis of perfluorooctane sulfonate
      using an excited xenon dimer lamp.
AB  - Vacuum ultraviolet (VUV) photolysis at the wavelength of 172 nm in a sulfate
      solution was introduced as a more efficient process for perfluorooctane sulfonate
      (PFOS) degradation than ultraviolet (UV) photolysis at 254 nm. The effects of pH
      and coexisting chemicals on VUV photolysis under the coexistence of 100 mM
      sulfate were investigated. VUV irradiation successfully degraded PFOS, and the
      degradation rate was 5.5 times higher than by UV photolysis. Direct VUV
      photolysis was inferred to mainly contribute to PFOS degradation. PFOS
      degradation by VUV irradiation was enhanced at pH less than 2 due to sulfate
      radicals generated via VUV photolysis of sulfate ions. Consequently, VUV
      photolysis was superior to UV photolysis for PFOS removal on both the removal
      rate and energy efficiency. However, the inorganic chemicals phosphoric acid and
      nitric acid strongly inhibited PFOS degradation, probably by masking PFOS from
      VUV rays by their VUV absorption. Accordingly, PFOS separation from inorganic
      materials such as phosphate and nitrate will be recommended for the application
      of VUV techniques for PFOS removal. In this research, organic solvent abstraction
      was inferred to be one of candidates for PFOS separation.

PMID- 29339610
TI  - Effect of precursor type on the reduction of concentrated nitrate using zero
      valent copper and sodium borohydride.
AB  - In this study, we demonstrated that the choice of precursor has a strong effect
      on the reduction of nitrate (NO3-) using zero-valent copper (Cu0) synthesized by
      sodium borohydride (NaBH4). Different precursors: CuSO4, CuO, Cu2O, Cu powder,
      and Cu mesh were used to reduce NO3- at 677 mg-N/L under the reducing conditions
      of NaBH4. Compared with the prehydrolyzed samples, those prepared without
      prehydrolysis exhibited lower reduction rates, longer times and higher
      concentrations of nitrite (NO2-) intermediate. It was found that one-time
      addition of NaBH4 resulted in higher reduction rate and less NO2- intermediate
      than two-step addition. Results showed that Cu0 from CuSO4 possessed the smallest
      particle size (890.9 nm), highest surface area (26.0 m2/g), and highest reaction
      rate (0.166 min-1). Values of pseudo-first-order constant (kobs) were in the
      order: CuSO4 > CuO > Cu2O > Cu powder >Cu mesh. However, values of surface area
      normalized reaction rate (kSA) were approximately equal. It was proposed that NO3
      was reduced to NO2- on Cu0, and then converted to NH4+ and N2, respectively; H2
      generated from both NaBH4 hydration and Cu (II) reduction contributed to NO3-
      reduction as well.

PMID- 29339611
TI  - Mechanism of 1,4-dioxane microbial degradation revealed by 16S rRNA and
      metatranscriptomic analyses.
AB  - 1,4-Dioxane (dioxane), a probable human carcinogen, often exists in industrial
      wastewater and domestic sewage. In this study, we applied 16S rRNA and
      metatranscriptomic methods to analyze the dioxane biodegradation mechanism by
      activated sludge. Tetrahydrofuran (THF) was added as an essential co-metabolite
      to promote the degradation of dioxane. We found the dioxane removal ratio
      increased with increasing THF concentrations. When the THF concentration
      increased from 60.0 to 200.0 mg/L, the dioxane degradation rate was stable. Three
      additions of ~60.0 mg/L THF resulted in better dioxane degradation than one
      addition of 200 mg/L THF. Ammonia-oxidizing and denitrifying bacteria with
      methane monooxygenases (MOs) and ammonia MOs played the most important roles
      during the degradation of dioxane. Kyoto Encyclopedia of Genes and Genomes
      metabolic pathway and functional genes analyses showed that the activated sludge
      system was complex and stable when dioxane was added. In future studies, primers
      should be designed to identify specific bacteria and functional MO genes, which
      would help reveal the function of various bacteria and their MOs during dioxane
      degradation.

PMID- 29339612
TI  - Industrial wastewater treatment with a bioelectrochemical process: assessment of
      depuration efficiency and energy production.
AB  - Development of renewable energy sources, efficient industrial processes,
      energy/chemicals recovery from wastes are research issues that are quite
      contemporary. Bioelectrochemical processes represent an eco-innovative technology
      for energy and resources recovery from both domestic and industrial wastewaters.
      The current study was conducted to: (i) assess bioelectrochemical treatability of
      industrial (dairy) wastewater by microbial fuel cells (MFCs); (ii) determine the
      effects of the applied organic loading rate (OLR) on MFC performance; (iii)
      identify factors responsible for reactor energy recovery losses (i.e.
      overpotentials). For this purpose, an MFC was built and continuously operated for
      72 days, during which the anodic chamber was fed with dairy wastewater and the
      cathodic chamber with an aerated mineral solution. The study demonstrated that
      industrial effluents from agrifood facilities can be treated by
      bioelectrochemical systems (BESs) with >85% (average) organic matter removal,
      recovering power at an observed maximum density of 27 W m-3. Outcomes were better
      than in previous (shorter) analogous experiences, and demonstrate that this type
      of process could be successfully used for dairy wastewater with several
      advantages.

PMID- 29339613
TI  - Sorption of Cr, Pb, Cu, Zn, Cd, Ni, and Co to nano-TiO2 in seawater.
AB  - In this study, the role of nanoparticles in complex aqueous matrices such as the
      Baltic Sea was investigated in batch-mode experiments in which titanium dioxide
      nanoparticles (nano-TiO2) were tested for their ability to remove heavy metals
      (Cr, Pb, Cu, Zn, Cd, Ni, Co) from multicomponent spiked and non-spiked Baltic Sea
      water. The experimental data were analyzed using different isotherms (Langmuir,
      Freundlich, Dubinin-Kaganer-Radushkevich (DKR)) and models (pseudo-first-order
      and pseudo-second-order models, the double-exponential model, and the Weber
      Morris model). The equilibria and kinetic investigations showed that metal
      sorption to nano-TiO2 occurs in a two-step, multilayer process and that there is
      strong competition for sorption sites. The results of the DKR isotherm and
      dilution experiment indicated weak electrostatic bonds, except for Pb. The
      distribution coefficient values (1.8 * 103 to 2.8 * 105 ml g-1) were consistent
      with the good sorbent properties of nano-TiO2 and supported the use of the
      particles in seawater purification technologies. However, metal-enriched nano
      TiO2 may also act as an effective carriers of metals to marine sediments, which
      could increase their availability to benthic organisms.

PMID- 29339614
TI  - Application of image processing on struvite recovery from swine wastewater by
      using the fluidized bed.
AB  - Fluidized granulation is one of the common methods used in wastewater treatment
      and resource recovery with harvesting millimeter-scale large particles.
      Presently, effective methods are lacking to measure the fluidized granules
      ranging from micro- to millimeter scales, with the consequence of ineffectively
      controlling and optimizing the granulation process. In this work, recovering
      struvite (MgNH4PO4.6H2O) from swine wastewater by using a fluidized bed was taken
      as an example. Image processing was applied to analyze the properties of
      different types of struvite granules, including morphology, particle size
      distribution, number density and mass concentration. Four stages of the struvite
      crystal evolution were therefore defined: aggregation, aggregate compaction,
      cluster-agglomerating and coating growth. These stages could occur simultaneously
      or sequentially. Up-flow rates of 30-80 mm/s in the fluidized bed sustained 600
      876 g/L granular solids. Results revealed that the coating-growth granules were
      formed with compact aggregates or cluster-agglomerating granules as the nuclei.
      The growth rates for the different types of particles, including population
      growth, mass increase and particle size enlargement, were determined. In final, a
      schematic illustration for struvite granulation process is also presented.

PMID- 29339615
TI  - Adsorption performance of polydopamine-modified attapulgite granular adsorbent
      for methylene blue.
AB  - Polydopamine-modified granule organo-attapulgite adsorbent (PDA-GOAT) was
      facilely prepared via a dip-coating approach. The samples were characterized by
      scanning electron microscopy, X-ray photoelectron spectroscopy and Fourier
      transform infrared spectroscopy. Surface area and pore size were calculated from
      the Brunauer-Emmett-Teller method by N2 adsorption-desorption isotherm. The
      adsorption behaviour of methylene blue (MB) onto PDA-GOAT was systematically
      investigated. The experimental data revealed that the adsorption process fitted
      well with the pseudo-second-order kinetics equation and the adsorption isotherm
      fitted better with the Langmuir model. Thermodynamic analyses illustrated that MB
      adsorption onto PDA-GOAT was a physisorption endothermic process. Importantly,
      PDA-GOAT can be regenerated by NaBH4 aqueous solution. The obtained results prove
      that PDA-GOAT can be a superior reusable adsorbent for the removal of MB from
      effluent.

PMID- 29339616
TI  - COD removal from leachate by electrocoagulation process: treatment with monopolar
      electrodes in parallel connection.
AB  - This study examines the removal of chemical oxygen demand (COD) from landfill
      leachate generated from the municipal landfill site of Bingol, Turkey. The effect
      of parameters such as current density, pH, and inter-electrode distance during
      the electrocoagulation (EC) process on COD removal of the process was
      investigated. Moreover, for COD removal, the energy consumption and operating
      costs were calculated for iron electrode under the EC conditions. COD removal
      efficiency was 72.13% at the current density of 16 mA m-2, pH of 8.05, and the
      inter-electrode distance of 9 mm at the detention time of 60 min with iron
      electrode and the COD concentration was reduced from 6,100 mg L-1 to 1,700 mg L-1
      by EC. The highest value of the electrical energy and electrode consumptions per
      kg of COD in the optimum conditions were determined as 0.055 kWh kg-1 COD and
      3.43 kg kg-1 COD and the highest operating cost value was found to be 1.41 US$ kg
      1 COD for 0-60 min time intervals.

PMID- 29339617
TI  - Characteristics of N2O production and hydroxylamine variation in short-cut
      nitrification SBR process.
AB  - In order to study the characteristics of nitrous oxide (N2O) production and
      hydroxylamine (NH2OH) variation under oxic conditions, concentrations of NH2OH
      and N2O were simultaneously monitored in a short-cut nitrification sequencing
      batch reactor (SBR) operated with different influent ammonia concentrations. In
      the short-cut nitrification process, N2O production was increased with the
      increasing of ammonia concentration in influent. The maximum concentrations of
      dissolved N2O-N in the reactor were 0.11 mg/L and 0.52 mg/L when ammonia
      concentrations in the influent were 50 mg/L and 70 mg/L respectively. Under the
      low and medium ammonia load phases, the concentrations of NH2OH-N in the reactor
      were remained at a low level which fluctuated around 0.06 mg/L in a small range,
      and did not change with the variation of influent NH4+-N concentration. Based on
      the determination results, the half-saturation of NH2OH in the biochemical
      conversion process of NH2OH to NO2--N was very small, and the value of 0.05 mg
      NH2OH-N/L proposed in the published literature was accurate. NH2OH is an
      important intermediate in the nitrification process, and the direct determination
      of NH2OH in the nitrification process was beneficial for revealing the kinetic
      process of NH2OH production and consumption as well as the effects of NH2OH on
      N2O production in the nitrification process.

PMID- 29339618
TI  - Rheological and electrical properties used to investigate the coagulation process
      during sludge treatment.
AB  - Analyses of rheological properties and electrical conductivity (sigmadc) at
      direct current have been employed in order to investigate the effects of calcium
      oxide on the coagulation process during sludge treatment in the textile industry.
      In this context, rheological and electrical measurements were performed on five
      samples - one that contained raw sludge and the other four that were prepared
      from the raw sludge and different amounts of calcium oxide: 2, 3, 4, 5% (w/w).
      Rheological behavior of these samples was analyzed using the Herschel-Bulkley
      modified model. The influence of calcium oxide content on the rheological
      parameters such as infinite viscosity, the yield stress, the consistency
      coefficient, and the consistency index, are presented and discussed. The impact
      of the calcium oxide content on pH and conductivity were also examined. Similar
      behaviors have been seen in the evolution of conductivity and infinite viscosity
      as a function of the calcium oxide content. These latter characteristics were
      modeled by an equation using two power laws. This equation was able to fit very
      well the evolution of electrical conductivity and also the viscosity versus the
      percentage of calcium oxide to predict the optimal amount of calcium oxide (3%)
      to achieve the coagulation step during sludge treatment.

PMID- 29339619
TI  - Improved sludge dewaterability and hydrolysis performance after pretreatment with
      Fenton's reagent.
AB  - The dewaterability of excess sludge significantly improved upon pretreatment with
      Fenton's reagent in this study. After 0.9 g/L of Fe2+ and 5.0 g/L of H2O2 were
      added to the sludge, and reacted for 2 h at pH = 4, the specific resistance to
      filtration (SRF) of the excess sludge decreased from an initial value of 29.74 *
      1012 m/kg to 6.49 * 1012 m/kg. The factors that affected this improvement in
      sludge dewaterability as evaluated by SRF reduction showed the following order:
      H2O2 > pH > Fe2+ > reaction time. Furthermore, the hydrolysis performance of the
      sludge under the optimal reaction conditions was investigated. The results
      indicated that the concentration of soluble chemical oxygen demand in the
      supernatant increased almost 14 times compared to raw sludge, and the contents of
      soluble protein and soluble polysaccharide were more than 8 and 17 times higher,
      respectively, than for the untreated situation. However, the amounts of ammonia
      nitrogen (NH4+-N) and phosphate (PO43--P) released from the sludge showed
      different trends: NH4+-N increased by 200%, while PO43--P decreased by 82%. The
      production of volatile fatty acids (VFAs) from the treated sludge showed that
      total VFAs increased by 66%, and iso-butylacetic acid was the dominant product
      among the total VFAs.

PMID- 29339620
TI  - The membrane fouling mechanisms of the PAC/BPAC-UF combined process used to treat
      the secondary effluent from municipal wastewater treatment plant.
AB  - The combined processes of powdered activated carbon/biological powdered activated
      carbon- ultrafiltration (PAC/BPAC-UF) were used to treat secondary effluent. In
      this study, the effect of PAC and BPAC on membrane flux, membrane resistance and
      the removal of different molecular weight organic compounds were investigated. In
      addition, the structure characteristics of the microorganisms of the BPAC were
      analyzed. The results showed that the optimum dosage of PAC and BPAC was 10 mg/L
      and 40 mg/L respectively. The reversible membrane fouling resistance of BPAC-UF
      was higher than that of PAC-UF, and the two processes had the least irreversible
      resistance at the best dosage. The biodegradation of BPAC increased the
      concentration of small molecular weight organic matter up to 10,000 Da in the
      membrane effluent. So the dissolved organic carbon (DOC) removal effect of BPAC
      UF process worsened. Microorganisms such as Proteobacteria, Bacteroidetes,
      Planctomycetes and other microorganisms on the surface of the BPAC enhanced the
      removal of organic matter in water. The results of scanning electron microscopy
      (SEM) scans showed that there was net mucus membrane on the UF membrane surface
      before the backwashing of the BPAC-UF process which increased the proportion of
      reversible pollution resistance. The physical flushing effect of BPAC-UF was
      better than that of direct UF and PAC-UF processes.

PMID- 29339621
TI  - Highly enhanced adsorption of Congo red by functionalized finger-citron-leaf
      based porous carbon.
AB  - A novel high-performance porous carbon material, lanthanum(III)-doped finger
      citron-leaf-based porous carbon (La/FPC), has been synthesized and used as an
      adsorbent for anion dye Congo red (CR). The La/FPC was characterized by nitrogen
      adsorption and desorption isotherms, scanning electron microscopy, transmission
      electron microscopy and X-ray photoelectron spectroscopy. The adsorption
      performance of CR by the FPC and La/FPC composites with different contents of
      lanthanum(III) were evaluated in fixed-bed breakthrough experiments and batch
      tests at room temperature (298 K). The La/FPC had a high CR uptake capacity,
      which was superior to those previously reported for other adsorbents. The La/FPC
      sorbents can be easily regenerated using an ethanol elution technique, and after
      five cycles the reused La/FPC maintained about 98% of its original CR adsorption
      capacity. The adsorption kinetics of CR onto the lanthanum(III)-doped FPCs
      followed a pseudo-second-order kinetic model and fitted well with a Langmuir
      adsorption isotherm. La/FPC is a promising adsorbent for the removal of the
      anionic dyes from wastewater.

PMID- 29339622
TI  - Identification of fouling mechanisms in MBRs at constant flowrate: model
      applications and SEM-EDX characterizations.
AB  - A fundamental understanding of fouling mechanisms is critical to improving
      filtration operations. The performance of four parallel membrane bioreactors
      (MBRs) with different sludge retention times (SRTs) was monitored during long
      term constant flowrate filtration. The characteristics of the membrane and
      transmembrane pressure (TMP) profiles obtained were studied to demonstrate
      fouling mechanisms. Both classical blocking models and their combined models were
      evaluated. The intermediate model provided very good agreement with all the TMP
      data. However, the combined cake-intermediate and intermediate-standard models
      were more effective in the description of the experimental data. Contributions
      analysis indicated that the cake, intermediate and standard blocking models were
      the dominant fouling mechanisms. Scanning electron microscopy and energy
      dispersive X-ray (SEM-EDX) imaging showed that cake blocking by organic matter
      and standard blocking by inorganic matter made the main contributions to membrane
      fouling. The combined cake-intermediate and intermediate-standard models may be
      applicable to systems where these two models are consistent with the
      experimentally observed fouling mechanisms in an MBR.

PMID- 29339623
TI  - Effects of scale and Froude number on the hydraulics of waste stabilization
      ponds.
AB  - This paper presents the findings from a series of computational fluid dynamics
      simulations to estimate the effect of scale and Froude number on hydraulic
      performance and effluent pollutant fraction of scaled waste stabilization ponds
      designed using Froude similarity. Prior to its application, the model was
      verified by comparing the computational and experimental results of a model
      scaled pond, showing good agreement and confirming that the model accurately
      reproduces the hydrodynamics and tracer transport processes. Our results showed
      that the scale and the interaction between scale and Froude number has an effect
      on the hydraulics of ponds. At 1:5 scale, the increase of scale increased short
      circuiting and decreased mixing. Furthermore, at 1:10 scale, the increase of
      scale decreased the effluent pollutant fraction. Since the Reynolds effect cannot
      be ignored, a ratio of Reynolds and Froude numbers was suggested to predict the
      effluent pollutant fraction for flows with different Reynolds numbers.

PMID- 29339624
TI  - The combined effects of carbon/nitrogen ratio, suspended biomass, hydraulic
      retention time and dissolved oxygen on nutrient removal in a laboratory-scale
      anaerobic-anoxic-oxic activated sludge biofilm reactor.
AB  - The current trend in sustainable development deals mainly with environmental
      management. There is a need for economically affordable, advanced treatment
      methods for the proper treatment and management of domestic wastewater containing
      excess nutrients (such as nitrogen and phosphorus) which can cause
      eutrophication. The reduction of the excess nutrient content of wastewater by
      appropriate technology is of much concern to the environmentalist. In the current
      study, a novel integrated anaerobic-anoxic-oxic activated sludge biofilm (A2O-AS
      biofilm) reactor was designed and operated to improve the biological nutrient
      removal by varying reactor operating conditions such as carbon to nitrogen (C/N)
      ratio, suspended biomass, hydraulic retention time (HRT) and dissolved oxygen
      (DO). Based on various trials, it was seen that the A2O-AS-biofilm reactor
      achieved good removal efficiencies with regard to chemical oxygen demand (95.5%),
      total phosphorus (93.1%), ammonia nitrogen concentration (NH4+-N) (98%) and total
      nitrogen (80%) when the reactor was maintained at C/N ratio of 4, suspended
      biomass of 3 to 3.5 g/L, HRT of 10 h, and DO of 1.5 to 2.5 mg/L. Scanning
      electron microscopy (SEM) of suspended and attached biofilm showed a dense
      structure of coccus and bacillus bacteria with the diameter ranging from 0.3 to
      1.2 MUm. The Fourier transform infrared (FTIR) spectroscopy results indicated
      phosphorylated macromolecules and carbohydrates mix or bind with extracellular
      proteins in exopolysaccharides.

PMID- 29339625
TI  - Acid production potentials of massive sulfide minerals and lead-zinc mine
      tailings: a medium-term study.
AB  - Weathering of sulfide minerals is a principal source of acid generation. To
      determine acid-forming potentials of sulfide-bearing materials, two basic
      approaches named static and kinetic tests are available. Static tests are short
      term, and easily undertaken within a few days and in a laboratory. In contrast,
      kinetic tests are long-term procedures and mostly carried out on site. In this
      study, experiments were conducted over a medium-term period of 2 months, not as
      short as static tests and also not as long as kinetic tests. As a result, pH and
      electrical conductivity oscillations as a function of time, acid-forming
      potentials and elemental contents of synthetically prepared rainwater leachates
      of massive sulfides and sulfide-bearing lead-zinc tailings from abandoned and
      currently used deposition areas have been determined. Although the lowest final
      pH of 2.70 was obtained in massive pyrite leachate, massive chalcopyrite leachate
      showed the highest titrable acidity of 1.764 g H2SO4/L. On the other hand, a
      composite of currently deposited mine tailings showed no acidic characteristic
      with a final pH of 7.77. The composite abandoned mine tailing leachate had a
      final pH of 6.70, close to the final pH of massive galena and sphalerite
      leachates, and produced a slight titrable acidity of 0.130 g H2SO4/L.

PMID- 29339626
TI  - Estimation of the dilution field near a marine outfall by using effluent
      turbidity as an environmental tracer and comparison with dye tracer data.
AB  - The alternative use of effluent turbidity to determine the dilution field of a
      domestic marine outfall located off the city of Rio de Janeiro was evaluated
      through field work comprising fluorescent dye tracer injection and tracking with
      simultaneous monitoring of sea water turbidity. A preliminary laboratory
      assessment was carried out with a sample of the outfall effluent whose turbidity
      was measured by the nephelometric method before and during a serial dilution
      process. During the field campaign, the dye tracer was monitored with field
      fluorometers and the turbidity was observed with an optical backscattering sensor
      interfaced to an OEM data acquisition system. About 4,000 samples were gathered,
      covering an area of 3 km * 3 km near the outfall diffusers. At the far field -
      where a drift towards the coastline was observed - the effluent plume was
      adequately labeled by the dye tracer. The turbidity plume was biased due to the
      high and variable background turbidity of sea water. After processing the
      turbidity dataset with a baseline detrending method, the plume presented high
      correlation with the dye tracer plume drawn on the near dilution field. However,
      dye tracer remains more robust than effluent turbidity.

PMID- 29339627
TI  - Corrigendum: Water Science and Technology 76 (2), 323-336 Detoxification of photo
      catalytically treated 2-chlorophenol: optimization through response surface
      methodology, doi: 10.2166/wst.2017.152.

PMID- 29339629
TI  - Utility of Routine Surveillance Imaging for Hodgkin Disease following Autologous
      Transplant: Experiences from a Single Institution.
AB  - BACKGROUND: Surveillance scans performed after autologous stem cell transplant
      (auto-HCT) for patients with Hodgkin disease (HD) have no proven survival
      benefit. METHODS: We studied survival differences among patients with HD after
      auto-HCT whose recurrences were detected on clinical history and exam, versus
      those detected on routine surveillance scan. RESULTS: Among the 98 patients with
      HD that underwent auto-HCT from 2000 to 2014 at our institution, 30 relapsed, of
      which 21 were detected radiologically and 9 clinically. There were no
      statistically significant differences in patient characteristics between the 2
      groups. The median time to progression was 118 days for the clinical cohort and
      284 days for the radiological cohort (p = 0.05). Median overall survival (OS) was
      728 days for the clinical cohort, and was not reached for the radiological cohort
      (p = 0.02). DISCUSSION: In our review, most patients with HD after auto-HCT were
      diagnosed radiologically. Patients whose relapse was diagnosed clinically were
      likely to be detected earlier and have a shorter OS. Patients with aggressive
      disease may be detected when clinically relevant, regardless of scanning. Routine
      scanning may not be necessary in the majority of patients with HD following auto
      HCT.

PMID- 29339628
TI  - Downregulation of Long Non-Coding RNA Kcnq1ot1: An Important Mechanism of Arsenic
      Trioxide-Induced Long QT Syndrome.
AB  - BACKGROUND/AIMS: Arsenic trioxide (ATO) is a known anti-acute promyelocytic
      leukemia (APL) reagent, whose clinical applications are limited by its serious
      cardiac toxicity and fatal adverse effects, such as sudden cardiac death
      resulting from long QT syndrome (LQTS). The mechanisms of cardiac arrhythmia due
      to ATO exposure still need to be elucidated. Long non-coding RNAs (lncRNAs) are
      emerging as major regulators of various pathophysiological processes. This study
      aimed to explore the involvement of lncRNAs in ATO-induced LQTS in vivo and in
      vitro. METHODS: For in vivo experiments, mice were administered ATO through the
      tail vein. For in vitro experiments, ATO was added to the culture medium of
      primary cultured neonatal mouse cardiomyocytes. To evaluate the effect of lncRNA
      Kcnq1ot1, siRNA and lentivirus-shRNA were synthesized to knockdown lncRNA
      Kcnq1ot1. RESULTS: After ATO treatment, the Kcnq1ot1 and Kcnq1 expression levels
      were down regulated. lncRNA Kcnq1ot1 knockdown prolonged the action potential
      duration (APD) in vitro and exerted LQTS in vivo. Correspondingly, Kcnq1
      expression was decreased after silencing lncRNA Kcnq1ot1. However, the knockdown
      of Kcnq1 exerted no effect on lncRNA Kcnq1ot1 expression. CONCLUSIONS: To our
      knowledge, this report is the first to demonstrate that lncRNA Kcnq1ot1
      downregulation is responsible for QT interval prolongation induced by ATO at
      least partially by repressing Kcnq1 expression. lncRNA Kcnq1ot1 has important
      pathophysiological functions in the heart and could become a novel antiarrhythmic
      target.

PMID- 29339631
TI  - Abstracts of Award-Winning Posters, 22nd Annual Health Sciences Poster
      Conference, Faculty of Medicine, Health Sciences Centre, Kuwait University,
      Kuwait, March 7-9, 2017: Abstracts.

PMID- 29339630
TI  - Comparison of the Efficacy of Different Drugs on Non-Motor Symptoms of
      Parkinson's Disease: a Network Meta-Analysis.
AB  - BACKGROUND/AIMS: A network meta-analysis is used to compare the efficacy of
      ropinirole, rasagiline, rotigotine, entacapone, apomorphine, pramipexole,
      sumanirole, bromocriptine, piribedil and levodopa, with placebo as a control, for
      non-motor symptoms in Parkinson's disease (PD). METHODS: PubMed, Embase and the
      Cochrane Library were searched from their establishment dates up to January 2017
      for randomized controlled trials (RCTs) investigating the efficacy of the above
      ten drugs on the non-motor symptoms of PD. A network meta-analysis combined the
      evidence from direct comparisons and indirect comparisons and evaluated the
      pooled weighted mean difference (WMD) values and surfaces under the cumulative
      ranking curves (SUCRA). The network meta-analysis included 21 RCTs. RESULTS: The
      analysis results indicated that, using the United Parkinson's Disease Rating
      Scale (UPDRS) III, the efficacies of placebo, ropinirole, rasagiline, rotigotine,
      entacapone, pramipexole, sumanirole and levodopa in treating PD were lower than
      that of apomorphine (WMD = -10.90, 95% CI = -16.12~-5.48; WMD = -11.85, 95% CI = 
      17.31~-6.16; WMD = -11.15, 95% CI = -16.64~-5.04; WMD = -11.70, 95% CI = -16.98~
      5.60; WMD = -11.04, 95% CI = -16.97~-5.34; WMD = -13.27, 95% CI = -19.22~-7.40;
      WMD = -10.25, 95% CI = -15.66~-4.32; and WMD = -11.60, 95% CI = -17.89~-5.57,
      respectively). Treatment with ropinirole, rasagiline, rotigotine, entacapone,
      pramipexole, sumanirole, bromocriptine, piribedil or levodopa, with placebo as a
      control, on PD exhibited no significant differences on PD symptoms when the UPDRS
      II was used for evaluation. Moreover, using the UPDRS III, the SUCRA values
      indicated that a pomorphine had the best efficacy on the non-motor symptoms of PD
      (99.0%). Using the UPDRS II, the SUCRA values for ropinirole, rasagiline,
      rotigotine, entacapone, pramipexole, sumanirole, bromocriptine, piribedil and
      levodopa treatments, with placebo as a control, indicated that bromocriptine
      showed the best efficacy on the non-motor symptoms of PD (75.6%). CONCLUSION:
      Among ropinirole, rasagiline, rotigotine, entacapone, apomorphine, pramipexole,
      sumanirole, bromocriptine, piribedil and levodopa, with placebo as a control,
      apomorphine may be the most efficacious drug for therapy in treating the non
      motor symptoms of PD.

PMID- 29339632
TI  - Identification of Rifampicin Resistance Mutations in Escherichia coli, Including
      an Unusual Deletion Mutation.
AB  - Rifampicin is an effective antibiotic against mycobacterial and other bacterial
      infections, but resistance readily emerges in laboratory and clinical settings.
      We screened Escherichia coli for rifampicin resistance and identified numerous
      mutations to the gene encoding the beta-chain of RNA polymerase (rpoB), including
      an unusual 9-nucleotide deletion mutation. Structural modeling of the deletion
      mutant indicates locations of potential steric clashes with rifampicin. Sequence
      conservation in the region near the deletion mutation suggests a similar mutation
      may also confer resistance during the treatment of tuberculosis.

PMID- 29339634
TI  - Abstracts of Theses Approved for MSc Degrees at the Faculty of Medicine, Health
      Sciences Center, Kuwait University, Kuwait: Abstracts.

PMID- 29339633
TI  - Multiple Sclerosis Mortality by Race/Ethnicity, Age, Sex, and Time Period in the
      United States, 1999-2015.
AB  - BACKGROUND: Multiple sclerosis (MS) carries high morbidity and shortens life
      span. While there is recent recognition of other US minority populations such as
      blacks and Hispanics being affected with MS, examination of MS-specific mortality
      trends by race/ethnicity has been lacking. OBJECTIVE: To investigate MS mortality
      rates and trends in the United States by sex, age, and race/ethnicity. METHODS:
      We used the Compressed Mortality data file for 1999-2015 in the Wide-ranging
      online Data for Epidemiological Research system developed by the Center for
      Disease Control and Prevention to calculate the age-adjusted (US 2000 standard
      population) and age-specific MS mortality rate (per 100,000) by race/ethnicity
      and sex over time. Five mutually exclusive racial/ethnic groups were included in
      the analysis: non-Hispanic (NH) white, NH black, NH Asian or Pacific Islander
      (API), NH American Indian or Alaska Native, and Hispanic. RESULTS: The average
      annual age-adjusted MS mortality rate was highest among NH whites (0.90 for males
      and 1.50 for females) immediately followed by NH blacks (0.75 for males and 1.42
      for females), and lowest among APIs (0.05 for males and 0.12 for females).
      Statistically significant, increasing trend in age-adjusted MS mortality was
      observed during 1999-2015 among NH whites and NH blacks regardless of sex, more
      substantially in the latter. Age-specific MS mortality patterns showed NH blacks
      had the highest rate under age 55 and NH whites had the highest rate after that
      age point. For these 2 groups, MS mortality increased with age in both sexes and
      peaked at ages 55-64 for NH blacks and 65-74 for NH whites before declining
      substantially, while for Hispanic and API groups the risk plateaued after age 55.
      CONCLUSION: MS-specific mortality trends demonstrate distinctive differences by
      race/ethnicity and age. The observations that whites and females are more likely
      to die from MS is in line with the overall understanding that these groups are
      affected more by MS. However, the findings of blacks dying at an earlier age and
      having more substantially increasing mortality trends than whites suggest that MS
      burden weighs unequally by race. Further investigation into these trends may
      provide additional evidence into risk or protective factors within each group.

PMID- 29339635
TI  - Response to the Letter to the Editor Regarding "Micronutrients, Essential Fatty
      Acids and Bone Health in Phenylketonuria".

PMID- 29339636
TI  - Successful Treatment of Autoimmune Urticaria with Low-Dose Prednisolone Therapy
      Administered for a Few Months: A Case Series of 42 Patients.
AB  - BACKGROUND: Chronic spontaneous urticaria (CSU) is defined as symptoms of
      urticaria persisting for 6 weeks or more without obvious cause. Autologous serum
      skin test (ASST) positivity in patients with CSU is considered to be associated
      with autoimmune urticaria (AIU). METHODS: In this retrospective study we
      retrieved the medical records of 1,073 urticaria patients seen at the Department
      of Dermatology and Allergology of Szeged University between January 2005 and
      February 2014. Forty-two patients (36 female and 6 male) met the study criteria
      by having CSU and giving positive results in the ASST. Our aim was to assess the
      clinical efficacy and safety of low-dose oral prednisolone therapy administered
      to patients with antihistamine-refractory ASST-positive CSU for a few months.
      Patients were given an initial dose (40 mg/day) of prednisolone until the
      complete resolution of the symptoms, usually 7-10 days, and then the dose was
      gradually decreased, as in other autoimmune diseases. RESULTS: Prednisolone
      therapy lasted for an average of 3.6 months and a complete long-lasting response
      was achieved in 35 of 42 AIU patients (83.3%). The follow-up period was at least
      36 months (3 years) for each AIU patient; the longest follow-up time was 139
      months (11.5 years). None of the patients reported any considerable side effects.
      CONCLUSION: Based on our results, we suggest that the use of this treatment could
      be an alternative for the treatment of AIU. Our present results also highlight
      the need for other therapies in a small percentage of AIU patients. Our results
      suggest that AIU represents a transient autoimmunity that can be successfully
      treated with low-dose steroid therapy administered for a few months.

PMID- 29339637
TI  - Corneal Collagen Crosslinking Combined with Phototherapeutic Keratectomy and
      Photorefractive Keratectomy for Corneal Ectasia after Laser in situ
      Keratomileusis.
AB  - PURPOSE: The aim of this study was to analyze the effects of corneal crosslinking
      (CXL) combined with phototherapeutic keratectomy (PTK) and photorefractive
      keratectomy (PRK) in halting the progression and improving the visual function of
      corneal ectasia after laser in situ keratomileusis (LASIK). METHODS: PTK-PRK-CXL
      was performed on 14 eyes of 14 patients who developed corneal ectasia after
      LASIK. The visual acuity, spherical refraction and cylinder, corneal topography
      indices, thinnest corneal thickness (TCT), and endothelial cell count were
      evaluated at baseline and at 1, 3, 6, and 12 months postoperatively. RESULTS: The
      mean uncorrected visual acuity improved significantly from 0.64 +/- 0.36 logMAR
      preoperatively to 0.19 +/- 0.12 logMAR at 12 months of follow-up (p < 0.001),
      while the mean best corrected visual acuity improved from 0.21 +/- 0.14 logMAR at
      baseline to 0.04 +/- 0.10 logMAR at 12 months postoperatively (p < 0.001). A
      significant decrease was observed in Kmax and Kmean values from 52.51 +/- 6.74
      and 43.55 +/- 3.37 D at baseline to 45.72 +/- 5.18 (p < 0.001) and 40.60 +/- 3.05
      D (p < 0.001) at the 1-year follow-up. The mean TCT decreased significantly from
      419.07 +/- 36.56 um before treatment to 320.93 +/- 39.78 um at 12 months of
      follow-up (p < 0.001), and there was no significant endothelial cell loss (p >
      0.05) beyond 6 months after treatment. CONCLUSION: PTK-PRK-CXL is a promising
      procedure to halt the progression of post-LASIK keratectasia with significant
      visual quality improvement.

PMID- 29339638
TI  - A Nomogram to Characterize the Severity of Detrusor Overactivity during the Ice
      Water Test: Description of the Method and Proof of Concept.
AB  - AIMS: To develop a nomogram with severity categories for detrusor overactivity
      (DO). METHODS: By conducting ice water tests (IWT) in 55 patients with
      Parkinson's disease, we identified criteria to describe characteristics of the
      detrusor pressure curves: (1) a gradient of Deltapdet over Deltat at the maximum
      detrusor pressure and (2) the area under the curve. In a nomogram, 10 severity
      categories of DO were established: 1 and 2 were assigned to group A (mild), 3 and
      4 to group B (moderate) and 5-10 to group C (severe). RESULTS: In the nomogram,
      negative IWT (20) appeared in category 1. Positive IWT (35) spread over the
      categories 1-8, 17 in group A, 11 in group B and 7 in categories 5-10. A
      relationship of incontinence episodes and nomogram category was observed. The
      nomogram category was reproducible in repeated IWT. Therapeutic interventions to
      treat DO lowered the nomogram category. CONCLUSION: From the relationship of
      detrusor pressure and time in the IWT, a nomogram with 10 severity categories of
      DO was developed. First observations show a relationship of nomogram category and
      the number of incontinence episodes, reproducibility in repeated tests and the
      representation of effects of therapeutic interventions to treat DO.

PMID- 29339639
TI  - MRI-Guided Interstitial Laser Ablation for Intracranial Lesions: A Large Single
      Institution Experience of 133 Cases.
AB  - BACKGROUND: Managing difficult-to-access lesions or surgically accessible lesions
      in fragile patients is a central problem in neurosurgery. MRI-guided interstitial
      laser ablation (ILA) is a minimally invasive option that may provide a safe means
      of treating these challenging patients. OBJECTIVE: We aim to (1) evaluate safety,
      efficacy, and preliminary outcomes within a diverse and large series of ILA
      treatments; and (2) report technical details and operative trends that proved
      useful over time in the authors' experience and that may be of use to
      neurosurgeons who perform ILA. METHODS: A retrospective evaluation of ILA
      patients was performed in terms of demographics, surgical techniques, and
      clinical outcomes. RESULTS: A total of 133 intracranial lesions in 120 patients
      were treated with ILA, including glioblastomas (GBM), other gliomas, metastases,
      epilepsy foci, and radionecrosis. The rate of complications/unexpected
      readmission was 6.0%, and the mortality rate was 2.2%. With high-grade tumors,
      tumor volumes >3 cm in diameter trended toward a higher rate of complication (p =
      0.056). Median progression-free survival (PFS) and overall survival (OS) for
      recurrent GBM were 7.4 and 11.6 months, respectively. As a frontline treatment
      for newly diagnosed GBM, median PFS and OS were 5.9 and 11.4 months,
      respectively. For metastases, median PFS was not yet reached, and OS was 17.2
      months. CONCLUSION: Our series suggests that ILA is a safe and efficacious
      treatment for a variety of intracranial pathologies, can be tailored to treat
      difficult-to-access lesions, and may offer a novel alternative to open craniotomy
      in properly selected patients.

PMID- 29339640
TI  - Application of Immunocytochemistry on Cell Block Sections for the Investigation
      of Thyroid Lesions.
AB  - OBJECTIVE: To investigate the potential of Classification and Regression Trees
      (CARTs) for the diagnosis of thyroid lesions based on cell block
      immunocytochemistry and cytological outcome. STUDY DESIGN: A total of 956
      histologically confirmed cases (673 benign and 283 malignant) from patients with
      thyroid nodules were prepared via liquid-based cytology and evaluated; 4
      additional slides were stained for cytokeratin 19 (CK-19), galectin 3 (Gal-3),
      Hector Battifora mesothelial cell 1 (HBME-1), and thyroglobulin. On the basis of
      immunocytochemistry and the cytological diagnosis, a CART algorithm was
      constructed and used for evaluation. RESULTS: The major important factors
      contributing to the diagnostic CART model were: cytological outcome, CK-19, Gal
      3, and HBME-1. The sensitivity and specificity of the cytological diagnosis were
      96.27% and 88.26%, respectively (cut-off: category 3 of The Bethesda System [TBS
      3]). The introduction of immunocytochemistry and the CART model increased the
      sensitivity and specificity to 98.88% and 99.11%, respectively. CK-19 presented
      the best performance for discriminating papillary thyroid carcinomas, followed by
      HBME-1 and Gal-3. In the TBS-2 cases, CK-19 and, subsequently, Gal-3 were
      important immunocytochemistry markers. Ultimately, CK-19 and HBME-1 on TBS-5 or
      TBS-6 cases demonstrated the best results. CONCLUSIONS: The hierarchical
      structure of the CART model provides a diagnostic algorithm linked with the risk
      of malignancy at every step of the procedure. It also provides guidance on the
      use of ancillary examinations as it goes by simple, human understandable rules.

PMID- 29339641
TI  - Longitudinal Assessment of Abdominal Circumference versus Estimated Fetal Weight
      in the Detection of Late Fetal Growth Restriction.
AB  - OBJECTIVES: To perform a longitudinal assessment comparison between estimated
      fetal weight (EFW) and abdominal circumference (AC) in the prediction of late
      fetal growth restriction (FGR) as opposed to small for gestational age (SGA).
      PATIENTS AND METHODS: A cohort of unselected singleton pregnancies scanned at
      32+/-2 and 37+/-1 weeks was created. Longitudinal growth assessment by
      calculating the conditional AC and conditional EFW was performed, and both
      parameters were compared for their prediction capacity for late FGR and SGA.
      Conditional standards set an expected size (EFW or AC) given a first measurement
      performed earlier. A declining growth was defined as a conditional growth of
      <10th centile. RESULTS: A total of 938 pregnancies were included. As expected,
      declining growth between 32+/-2 and 37+/-1 weeks was associated with late FGR and
      SGA, but the predictive capacity of both conditional AC and conditional EFW was
      comparably poor, with detection rates of 28% at a 10% rate of false positives for
      late FGR. CONCLUSIONS: Longitudinal assessment of fetal growth during the third
      trimester has a low predictive capacity for late FGR, with no differences between
      conditional AC and conditional EFW.

PMID- 29339642
TI  - Significance of Salvage Autologous Stem Cell Transplantation for Relapsed
      Multiple Myeloma: A Nationwide Retrospective Study in Japan.
AB  - Autologous stem cell transplantation (ASCT) has been employed for patients with
      relapsed multiple myeloma (MM) after up-front ASCT. The present retrospective
      study aimed to examine the survival benefit from salvage ASCT. Among 446 patients
      with relapsed MM after up-front single ASCT, 70 patients received salvage ASCT,
      the employment of which reduced the risk of mortality after relapse (p = 0.041).
      Using the parameters before initial ASCT, the advantage of salvage ASCT compared
      to standard therapy was confirmed in the subgroup with an international staging
      system stage of I or II (p = 0.040), good performance status (PS; p = 0.043), or
      no/mild renal comorbidity (p = 0.029). The advantage of salvage ASCT was also
      confirmed in the subgroup excluding those with early relapse within 7 months
      after initial ASCT (p = 0.026). Among patients who received salvage ASCT, a
      favorable prognosis is apparent for those with a time to relapse after initial
      ASCT of longer than 24 months. The overall survival after salvage ASCT was
      favorable excluding patients with the following factors: early relapse, poor PS,
      moderate/severe renal comorbidity, and progressive disease (p < 0.001). In
      conclusion, our results reinforced the evidence for encouraging salvage ASCT for
      eligible patients.

PMID- 29339643
TI  - Effect of Remote Ischemic Preconditioning on Systemic Toxicity and Ototoxicity
      Induced by Cisplatin in Rats: Role of TNF-alpha and Nitric Oxide.
AB  - BACKGROUND/AIMS: Cisplatin is a chemotherapeutic agent. The use of remote
      ischemic preconditioning (RIPC) was proposed after the observation that ischemic
      preconditioning of a cardiac vascular area could protect another completely
      distinctly. METHODS: This is an experimental study. Male Wistar rats were
      anesthetized, and they underwent a hearing evaluation via measurement of the
      brainstem auditory evoked potential (BSAEP). Then, cisplatin was administered
      intraperitoneally (IP) at a dose of 8 mg/kg/day for 4 consecutive days to group
      1, whereas saline solution was administered IP to group 2. In groups 3 and 4,
      ischemia of the right hind paw was performed for 10 min, followed by reperfusion
      for 30 min, after which cisplatin or saline was administered IP to group 3 or
      group 4, respectively. Afterwards, all animals were evaluated via the BSAEP. The
      right cochlea was dissected for immunohistochemistry. RESULTS: RIPC lowered the
      increase in BSAEP of the animals treated with cisplatin (p = 0.0146). Weight loss
      decreased in the animals subjected to RIPC (p < 0.005). In group 3, RIPC reversed
      immunostaining for tumor necrosis factor-alpha and inducible nitric oxide
      synthase in the stria vascularis injured by cisplatin (p < 0.05). CONCLUSION:
      RIPC protects against systemic toxicity and ototoxicity induced by cisplatin in
      rats.

PMID- 29339644
TI  - Changes in Central Macular Thickness and Retinal Nerve Fiber Layer Thickness in
      Eyes with Vogt-Koyanagi-Harada Disease: A 2-Year Follow-Up Study.
AB  - PURPOSE: To investigate the central macular thickness (CMT) and retinal nerve
      fiber layer (RNFL) thickness in eyes with Vogt-Koyanagi-Harada (VKH) disease
      associated with optic disc swelling and serous retinal detachment through a 24
      month follow-up period. METHODS: We prospectively investigated 28 eyes of 14
      treatment-naive patients with acute VKH disease associated with optic disc
      swelling and serous retinal detachment and 30 eyes of 15 normal individuals to
      compare changes in the CMT and average RNFL thickness. RESULTS: The CMT was
      significantly lower in the eyes of the VKH group at 12 and 24 months. The RNFL
      thickness was significantly higher in the eyes of the VKH group at the initial
      visit and at the 6- and 12-month follow-up visits, but no significant difference
      was found between the VKH group and control group at the 24-month follow-up
      visit. CONCLUSION: Significant changes in the CMT and RNFL thickness in the eyes
      with VKH disease were observed during the 24-month follow-up period. When
      diagnosing or monitoring diseases including glaucoma and neuro-ophthalmic
      diseases that affect the retinal thickness in patients with VKH disease, we
      recommend considering longitudinal changes in the retinal thickness.

PMID- 29339645
TI  - Multi Matrix System Mesalazine Plus Rectal Mesalazine in the Treatment of Mild to
      Moderately Active Ulcerative Proctitis.
AB  - BACKGROUND: Mesalazine 1 g suppository/die is used for mild to moderately active
      ulcerative proctitis (UP). Whether addiction of Multi Matrix System (MMX)
      mesalazine increases the remission rate of UP and prevents proximal extension of
      disease is unknown. METHODS: This is a retrospective study on 116 outpatients
      with UP who had been treated with one of the following regimens: (1) MMX
      mesalazine 1.2 g/die plus mesalazine suppositories for 8 +/- 2 weeks and,
      subsequently, MMX mesalazine 1.2 g/die plus rectal mesalazine 1 g every other day
      for at least 6 months; (2) mesalazine 1 g suppositories/die alone for 8 +/- 2
      weeks and, subsequently, rectal mesalazine 1 g every other day for 6 more months.
      Patients were evaluated clinically at 2 months (+/-2 weeks) and endoscopically at
      6 months (+/-2 weeks). For categorical variables, Pearson chi-square test was
      used. RESULTS: A total of 46 of 55 patients (84%) on combined therapy and 49 of
      61 patients (80%) on rectal mesalazine reached clinical remission (p > 0.05; OR
      0.79, 95% CI 0.30-2.07). At 6 months follow-up, proximal extension of disease was
      observed in 7 of 55 (14%) patients on combined therapy and in 18 of 61 (29%)
      patients on rectal mesalazine alone (p < 0.05; OR 2.87, 95% CI 1.09-7.53).
      CONCLUSIONS: Oral MMX mesalazine plus rectal mesalazine combined treatment is
      associated with prevention of proximal extension of the disease compared with
      rectal mesalazine alone.

PMID- 29339646
TI  - Automated Screening for Diabetic Retinopathy - A Systematic Review.
AB  - PURPOSE: Worldwide ophthalmologists are challenged by the rapid rise in the
      prevalence of diabetes. Diabetic retinopathy (DR) is the most common complication
      in diabetes, and possible consequences range from mild visual impairment to
      blindness. Repetitive screening for DR is cost-effective, but it is also a costly
      and strenuous affair. Several studies have examined the application of automated
      image analysis to solve this problem. Large populations are needed to assess the
      efficacy of such programs, and a standardized and rigorous methodology is
      important to give an indication of system performance in actual clinical
      settings. METHODS: In a systematic review, we aimed to identify studies with
      methodology and design that are similar or replicate actual screening scenarios.
      A total of 1,231 publications were identified through PubMed, Cochrane Library,
      and Embase searches. Three manual search strategies were carried out to identify
      publications missed in the primary search. Four levels of screening identified 7
      studies applicable for inclusion. RESULTS: Seven studies were included. The
      detection of DR had high sensitivities (87.0-95.2%) but lower specificities (49.6
      68.8%). False-negative results were related to mild DR with a low risk of
      progression within 1 year. Several studies reported missed cases of diabetic
      macular edema. A meta-analysis was not conducted as studies were not suitable for
      direct comparison or statistical analysis. CONCLUSION: The study demonstrates
      that despite limited specificity, automated retinal image analysis may
      potentially be valuable in different DR screening scenarios with a relatively
      high sensitivity and a substantial workload reduction.

PMID- 29339647
TI  - Proceedings of the 11th Congress of the International Society of Nutrigenetics
      and Nutrigenomics (ISNN 2017).
AB  - The International Society of Nutrigenetics and Nutrigenomics (ISNN) held its 11th
      annual Congress in Los Angeles, California, between September 16 and 19, 2017. In
      addition to 2 keynote lectures, 4 plenary sessions included presentations by
      internationally renowned speakers on cutting-edge areas of research and new
      discoveries in genetics/genomics, the microbiome, and nutrition. Scientific
      topics included multi-omics approaches; diet and the microbiome; cancer,
      longevity, and metabolism; moving the field forward; and
      translational/educational aspects and the future of medicine. There was also an
      accepted oral abstracts session designed specifically to provide young
      investigators and trainees with the opportunity to present their work, as well as
      a session focused on industry-academic partnerships, which included a roundtable
      discussion afterwards. Overall, the 11th ISNN Congress was an exciting and
      intellectually stimulating meeting focused on understanding the impact of
      biological interactions between genes and nutrients on health and disease. These
      efforts continued the decade-long tradition of the annual ISNN Congress to
      provide an interdisciplinary platform for scientists from various disciplines to
      discuss research ideas and advance the fields of nutrigenetics and nutrigenomics.

PMID- 29339648
TI  - Caries-Preventive Effect of NaF, NaF plus TCP, NaF plus CPP-ACP, and SDF
      Varnishes on Sound Dentin and Artificial Dentin Caries in vitro.
AB  - The aim of this study was to compare the caries-preventive effect of different
      fluoride varnishes on sound dentin as well as on artificial dentin caries-like
      lesions. Bovine dentin specimens (n = 220) with one sound surface (ST) and one
      artificial caries lesion (DT) were prepared and randomly allocated to 11 groups.
      The interventions before pH cycling were as follows: application of a varnish
      containing NaF (22,600 ppm F-; Duraphat [NaF0/NaF1]), NaF plus tricalcium
      phosphate (22,600 ppm F-; Clinpro White Varnish Mint [TCP0/TCP1]), NaF plus
      casein phosphopeptide-stabilized amorphous calcium phosphate complexes (CPP-ACP;
      22,600 ppm F-; MI Varnish [CPP0/CPP1]), or silver diamine fluoride (SDF; 35,400
      ppm F-; Cariestop 30% [SDF0/SDF1]) and no intervention (NNB/N0/N1). During pH
      cycling (14 days, 6 * 120 min demineralization/day) half of the specimens in each
      group were brushed (10 s; 2 times/day) with either fluoride-free ("0"; e.g.,
      TCP0) or 1,100 ppm F- ("1"; e.g., TCP1) dentifrice slurry. In another subgroup,
      the specimens were pH cycled but not brushed (NNB). Differences in integrated
      mineral loss (DeltaDeltaZ), lesion depth (DeltaLD), and colorimetric values
      (DeltaDeltaE) were calculated between the values after initial demineralization
      and those after pH cycling, using transversal microradiography and photographic
      images. After pH cycling, no discoloration could be observed. Furthermore, NNB,
      N0, and N1 showed significantly increased DeltaZDT/LDDT and DeltaZST/LDST values,
      indicating further demineralization. In contrast, CPP0, CPP1, SDF0, and SDF1
      showed significantly decreased DeltaZDT/LDDT values, indicating remineralization
      (p <= 0.004; paired t test). CPP0, CPP1, SDF0, and SDF1 showed significantly
      higher changes in DeltaDeltaZDT/DeltaLDDT and DeltaDeltaZST/DeltaLDST than NNB,
      N0, and N1 (p < 0.001; Bonferroni post hoc test). In conclusion, under the
      conditions chosen, all fluoride varnishes prevented further demineralization.
      However, only NaF plus CPP-ACP and SDF could remineralize artificial dentin
      caries-like lesions under net-demineralizing conditions, thereby indicating that
      NaF plus CPP-ACP and SDF may be helpful to high-caries-risk patients.

PMID- 29339649
TI  - Cardiovascular Risk Factors and Insulin Resistance after Two Hypocaloric Diets
      with Different Fat Distribution in Obese Subjects: Effect of the rs10767664 Gene
      Variant in Brain-Derived Neurotrophic Factor.
AB  - BACKGROUND: The role of brain-derived neurotrophic factor (BDNF) variants on
      change in body weight and cardiovascular risk factors after weight loss remains
      unclear in obese patients. OBJECTIVE: Our aim was to analyze the effects of the
      rs10767664 BDNF gene polymorphism on body weight, cardiovascular risk factors,
      and serum adipokine levels after a high monounsaturated fatty acids (MUFAs)
      hypocaloric diet (diet M) versus a high polyunsaturated fatty acids (PUFAs)
      hypocaloric diet (diet P). METHODS: A Caucasian population of 361 obese patients
      was enrolled. Subjects who met the inclusion criteria were randomly allocated to
      one of two diets for a period of 3 months. RESULTS: Two hundred and sixteen
      subjects (59.8%) had the genotype AA (wild-type group), and 145 (40.2%) patients
      had the genotypes AT (122 patients, 33.8%) or TT (23 patients, 6.4%) (mutant-type
      group). After weight loss with diet P and diet M and in both genotype groups,
      body mass index, weight, fat mass, waist circumference, systolic blood pressure,
      serum leptin levels, low-density lipoprotein cholesterol, and total cholesterol
      decreased in a significant way. Secondary to weight loss with diet M and only in
      the wild-type group, insulin levels (-2.1 +/- 2.0 vs. -0.7 +/- 2.9 IU/L, p <
      0.05) and homeostatic model assessment of insulin resistance (-0.7 +/- 0.9 vs. 
      0.3 +/- 1.0 U, p < 0.05) decreased. CONCLUSION: Our data show that the rs10767664
      variant of the BDNF gene modifies insulin resistance and insulin levels after
      weight loss with a hypocaloric diet enriched with MUFAs.

PMID- 29339650
TI  - Oral Immunotherapy in Japanese Children with Anaphylactic Peanut Allergy.
AB  - BACKGROUND: Reports on oral immunotherapy (OIT) for anaphylactic food allergy are
      lacking. We investigated the efficacy and safety of peanut OIT for anaphylactic
      patients. METHODS: We enrolled 22 peanut anaphylactic patients who underwent OIT
      between 2011 and 2013, all of whom demonstrated anaphylaxis during a baseline
      double-blind, placebo-controlled food challenge. After starting in-hospital OIT,
      participants gradually increased ingestion to 795 mg of peanut protein per day at
      home and then took a maintenance dose (795 mg) daily. After 3 asymptomatic
      months, participants underwent an oral food challenge (OFC) of 795 mg after 2
      weeks of peanut avoidance to confirm sustained unresponsiveness. The historical
      control group consisted of 11 patients with anaphylaxis by OFC and underwent the
      second OFC after 2 years. RESULTS: All patients (22/22) achieved desensitization
      by 8 months after starting OIT and completed the protocol within 2 years. Two
      years later, 15/22 patients (68.1%) in the OIT group achieved sustained
      unresponsiveness, whereas only 2 (18.1%) in the control group passed the second
      OFC. After 2 years, the median peanut-specific IgE had significantly decreased
      (from 38.5 to 12.4 kUA/L) in the OIT group, but not in the control group. Median
      peanut- and Ara h 2-specific IgG4 in the OIT group had significantly increased
      from baseline after 1 month. The adverse reaction rate per ingestion was 43% in
      hospital and 5% at home. Three patients received adrenaline at the hospital and 2
      at home. CONCLUSIONS: These data suggest that for patients with peanut
      anaphylaxis, OIT can increase the threshold and support achieving sustained
      unresponsiveness with relative safety.

PMID- 29339651
TI  - Albumin-Indocyanine Green Evaluation Grading System Predicts Post-Hepatectomy
      Liver Failure for Biliary Tract Cancer.
AB  - BACKGROUND: In biliary tract cancer treatment, a precise preoperative evaluation
      of the patient's liver function is essential to avoid post-hepatectomy liver
      failure (PHLF) and mortality. The present study aimed to evaluate the role of the
      Albumin-Indocyanine Green Evaluation (ALICE) grading system in predicting PHLF in
      biliary tract cancer patients. METHODS: Data from 166 patients who underwent
      hepatectomy for biliary tract cancer between 2000 and 2016 were retrospectively
      analyzed. Univariate and multivariate analyses were performed to identify the
      risk factors for PHLF. RESULTS: Among the 166 patients, major hepatectomy was
      performed in 101 (61%) and bile duct resection was performed in 99 (60%)
      patients. Thirteen (8%) patients developed PHLF. Furthermore, PHLF, major
      complications, and mortality were significantly higher in patients with high
      ALICE grades (>=2b) than in those with low ALICE grades (<2b) (PHLF, 42 vs. 18%,
      p = 0.002; major complications, 35 vs. 19%, p = 0.036; mortality, 9.3 vs. 0%, p =
      0.001). In multivariate analysis, high ALICE grade (p = 0.016) and blood loss
      >=1,500 mL (p = 0.009) were identified as independent risk factors for PHLF.
      CONCLUSIONS: The ALICE grading system effectively stratified the risks for PHLF
      for biliary tract cancer.

PMID- 29339652
TI  - Smoking and Promoter-Specific Deoxyribonucleic Acid Methylation of the Atrial
      Natriuretic Peptide Gene: Methylation of Smokers and Non-Smokers Differs
      Significantly during Withdrawal.
AB  - BACKGROUND: Atrial natriuretic peptide (ANP) is well known in psychiatric
      disorders to modulate hypothalamic-pituitary-adrenal axis activity. Disturbances
      of ANP have been described in early abstinent alcohol-dependent patients. This is
      the first longitudinal investigation on cytosine-phosphatidyl-guanine (CpG)
      island promoter methylation of the ANP gene in the blood of tobacco-dependent
      patients. METHODS: In a longitudinal approach, we investigated whether changes in
      ANP serum levels correlated to CpG methylation of the respective gene promoters
      on days 1, 7, and 14 of tobacco withdrawal. RESULTS AND CONCLUSION: Compared to
      non-smokers, promoter-related deoxyribonucleic acid methylation of the ANP
      promoter was significantly elevated on days 7 and 14 of withdrawal in tobacco
      dependent patients. Baseline methylation status of the ANP promoter was not
      significantly different from controls, arguing for an impaired regulation during
      withdrawal.

PMID- 29339653
TI  - Adherence to the European Association of Urology Guidelines: A National Survey
      among Italian Urologists.
AB  - OBJECTIVE: The study aimed to explore adherence to the European Urological
      Association (EAU) Guidelines (GLs) grade A recommendation among Italian
      urologists. MATERIALS AND METHODS: A 13-item multiple-choice questionnaire
      covering oncological and non-oncological urological diseases was e-mailed to all
      Italian Urologist Society (Societa Italiana di Urologia or SIU) members. We asked
      members to provide an explanation for their answer choice where needed. The
      quantitative data were tested using the Pearson's chi-square test. For all
      statistical comparisons, significance was considered as p < 0.05. RESULTS: Of the
      2011 invited SIU members, 210 (10.4%) completed the survey. The sample was
      composed of 22 (10.5%) Academic Urologists (AcUs), 110 (52.4%) Attending
      Urologists (AtUs), 32 (15.2%) Private Practice Urologists (PPUs), and 41 (19.5%)
      Residents in Urology (RUs). The mean adherence to the EAU Oncologic GLs ranged
      from 54.5 to 97.1%, while the adherence to the non-oncologic GLs ranged from 45
      to 87.6%. We found that adherence differed across the working categories
      assessed. CONCLUSION: Our survey showed that professional role, updates, and
      local facilities seem to be the drivers that influence the non-adherence to the
      GLs. Urologists who work in university hospital would be more inclined to adopt
      the GLs compared to those who practice in non-academic centers.

PMID- 29339654
TI  - Comparative Burden of Subclinical Tremor in a Cohort of Normal Individuals
      Stratified by Familial Risk for Essential Tremor.
AB  - BACKGROUND: The burden of mild (i.e., subclinical) tremor within essential tremor
      (ET) families is not fully understood. We assessed the burden of mild tremor in a
      cohort of 287 adults, none of whom reported tremor or were diagnosed with ET.
      METHODS: We recruited adults in 2 groups based on the familial risk for ET: 244
      high-risk individuals (i.e., reporting one or more first-degree relative with ET)
      and 43 low-risk individuals (i.e., reporting no relatives with ET). Tremor was
      objectively assessed on 4 hand-drawn spirals (total spiral score = 0-12). Mild
      tremor was defined using 3 different cut points. RESULTS: The prevalence rates of
      mild tremor among high-risk individuals ranged from 41.4 to 98.4% and were highly
      dependent on the cut point. Above a certain threshold (i.e., a total spiral score
      >=5), 1-in-5 (i.e., 19.7%) high-risk individuals exhibited mild tremor, whereas
      no low-risk individuals did. High-risk individuals were 3.09-4.50 times more
      likely than low-risk individuals to exhibit mild tremor. CONCLUSION: The burden
      of ET extends beyond the boundaries of the clinically defined disease, and
      partially expressed forms of ET are abundant in ET families. This fact greatly
      complicates gene-finding studies and epidemiological studies whose goal is to
      detect disease-linked associations.

PMID- 29339655
TI  - The Impact of Arterial Clamping Technique in Robot-Assisted Partial Nephrectomy
      on Renal Function and Surgical Outcomes: Six-Year Experience at Siriraj Hospital,
      Thailand.
AB  - INTRODUCTION: Robot-assisted partial nephrectomy (RAPN) with different arterial
      clamping techniques has increasingly been performed to avoid ischemic injury to
      nephron. However, postoperative renal function remains controversial. We
      determine the impact of each renal arterial clamping on surgical and renal
      outcomes after RAPN. MATERIALS AND METHODS: Patients who underwent RAPN at
      Siriraj Hospital from 2010 to 2016 were retrospectively reviewed and stratified
      into 3 cohorts: main-clamp (MAC), selective-clamp, and off-clamp. RESULTS: Main,
      selective, and off-clamping were performed in 27, 38, and 12, respectively.
      Median tumor size and Radius, Exophytic or endophytic, Nearness to collecting
      system or sinus, Anterior or posterior, and Location relative to polar lines
      (RENAL) score were 3 cm and 7, respectively. Longer operative time was observed
      in MAC (p = 0.002) although estimated blood loss, transfusion rate, and
      complication were comparable. Warm ischemia time was not different between
      cohorts. However, number of patients with prolonged ischemia time in MAC were
      greater (p <= 0.01). All margins were negative. Median postoperative and latest
      glomerular filtration rate reduction were 3.8 and 5.3 mL/min/1.73 m2,
      respectively without significant difference between cohorts. On multivariable
      analysis, hypertension independently associated with reduced renal function
      preserved (p = 0.03). Median follow-up was 18 months. CONCLUSIONS: Our study is
      the first to report surgical and renal functional outcomes after RAPN in
      Southeast-Asian population. Based on our experience, clamping techniques does not
      impact on renal functions and complication rate was low even in small-volume
      center.

PMID- 29339656
TI  - New: The European Addiction Research Award.

PMID- 29339657
TI  - The Practical Management of Chronic Pancreatitis: A Multidisciplinary Symposium
      Held at the Annual Meeting of the Pancreatic Society of Great Britain and
      Ireland, Manchester 2016.
AB  - AIM: This study is about a questionnaire survey of delegates attending the
      chronic pancreatitis symposium at the 2016 meeting of the Pancreatic Society of
      Great Britain and Ireland and seeks a multidisciplinary "snapshot" overview of
      practice. METHODS: A questionnaire was developed with multidisciplinary input.
      Questions on access to specialist care, methods of diagnosis and treatment
      including specific scenarios were incorporated. Eighty-three (66%) of 125
      delegates effectively participated in this survey. RESULTS: Twenty-four (29%) had
      neither a chronic pancreatitis MDT in their hospital nor a chronic pancreatitis
      referral MDT. Most frequently utilised diagnostic modalities were CT, MR and EUS
      with no respondents utilising duodenal intubation tests. Initial treatment was
      provided through non-opiate analgesia by 69 (93%), through the use of opiates by
      56 (76%) and through the use of co-analgesics by 49 (66%). Fifty two (68%)
      routinely referred patients with alcohol-related disease for counselling.
      Preferred treatment for large duct disease without mass was endoscopic therapy.
      In older patients with a mass, pancreaticoduodenectomy was preferred. CONCLUSION:
      This is a small study likely to be skewed by sampling bias but is thought to be
      the first multidisciplinary survey of the management of chronic pancreatitis in
      the United Kingdom and Ireland. The results show a need for comprehensive access
      to specialist pancreatitis MDT care and there remains substantial variation in
      management.

PMID- 29339658
TI  - Survey Results of the Expert Meeting on Laparoscopic Surgery for Gallbladder
      Cancer and a Review of Relevant Literature.
AB  - BACKGROUND: Favorable outcomes of laparoscopic surgery for gallbladder cancer
      (GBC) have been reported; yet consensus on the indications and surgical
      techniques for laparoscopic surgery for GBC is lacking. OBJECTIVE: To evaluate
      the current status of laparoscopic surgery for GBC by analyzing the results of a
      survey of experts and by reviewing the relevant published literature. METHODS:
      Before an expert meeting was held on September 10, 2016 in Seoul, Korea, an
      international survey was undertaken of expert surgeons in the field of GBC
      surgery. RESULTS: The majority of surgeons who responded agreed that laparoscopic
      surgery has an acceptable role for suspicious or early GBC, and that laparoscopic
      extended cholecystectomy has a value comparable to that of open surgery in
      selected patients with GBC. However, the selection criteria for laparoscopic
      surgery for overt GBC and the details of the surgical techniques varied among
      surgeons. CONCLUSIONS: This survey and literature review revealed that
      laparoscopic surgery for GBC is performed in highly selected cases. However, the
      favorable outcomes in the published reports and the positive view of experienced
      surgeons for this operative procedure suggest a high likelihood that laparoscopic
      surgery will be more frequently performed for GBC in the future.

PMID- 29339659
TI  - FcgammaR/ROS/CK2alpha Is the Key Inducer of NF-kappaB Activation in a Murine
      Model of Asthma.
AB  - BACKGROUND: The transcription factor nuclear factor (NF)-kappaB plays a pivotal
      role in the development of allergic airway inflammation. However, the mechanism
      of NF-kappaB activation in asthma remains to be elucidated. METHODS: CK2alpha
      activation was assessed by CK2alpha phosphorylation and protein expression.
      Airway levels of histamine and cytokines were determined by ELISA. We used 2
      (active and passive) forms of allergic pulmonary inflammation models. In the
      active form, the animals were immunized with ovalbumin (OVA) intraperitoneally,
      followed by an airway challenge with OVA. In the passive form, the animals were
      passively sensitized by intratracheal instillation with either anti-OVA IgE or
      anti-OVA IgG, followed by an airway challenge with OVA. The role of NADPH oxidase
      (NOX) in CK2alpha activation was assessed using NOX2-/- and NOX4-/- mice because
      NOX2 and NOX4 contribute to many inflammatory diseases. RESULTS: The second
      airway challenge increased CK2alpha phosphorylation and protein expression in
      airway epithelial cells as well as nuclear translocation of the p50 and p65
      subunits of NF-kappaB, all of which were inhibited by the CK2alpha inhibitor
      4,5,6,7-tetrabromobenzotriazole and the antioxidant N-acetyl-L-cysteine. CK2alpha
      phosphorylation and protein expression were significantly impaired in NOX2-/-,
      but not in NOX4-/-, mice. Induction of passive sensitization using anti-OVA IgE
      activated neither CK2alpha nor NF-kappaB. In contrast, induction of passive
      sensitization using anti-OVA IgG activated both CK2alpha and NF-kappaB.
      CONCLUSIONS: These data suggest that Fcgamma receptor/reactive oxygen
      species/CK2alpha is a key inducer of NF-kappaB activation in airway epithelial
      cells in a murine model of asthma.

PMID- 29339660
TI  - Laparoscopic Surgery for Gallbladder Cancer: An Expert Consensus Statement.
AB  - BACKGROUND: Despite the increasing number of reports on the favorable outcomes of
      laparoscopic surgery for gallbladder cancer (GBC), there is no consensus
      regarding this surgical procedure. OBJECTIVE: The study aimed to develop a
      consensus statement on the application of laparoscopic surgery for GBC based on
      expert opinions. METHODS: A consensus meeting among experts was held on September
      10, 2016, in Seoul, Korea. RESULTS: Early concerns regarding port site/peritoneal
      metastasis after laparoscopic surgery have been abated by improved preoperative
      recognition of GBC and careful manipulation to avoid bile spillage. There is no
      evidence that laparoscopic surgery is associated with decreased survival compared
      with open surgery in patients with early-stage GBC if definitive resection
      during/after laparoscopic cholecystectomy is performed. Although experience with
      laparoscopic extended cholecystectomy for GBC has been limited to a few experts,
      the postoperative and survival outcomes were similar between laparoscopic and
      open surgeries. Laparoscopic reoperation for postoperatively diagnosed GBC is
      technically challenging, but its feasibility has been demonstrated by a few
      experts. CONCLUSIONS: Laparoscopic surgery for GBC is still in the early phase of
      the adoption curve, and more evidence is required to assess this procedure.

PMID- 29339661
TI  - A Novel FOXL2 Mutation Implying Blepharophimosis-Ptosis-Epicanthus Inversus
      Syndrome Type I.
AB  - BACKGROUND/AIMS: Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is a
      rare autosomal dominant disease caused by FOXL2 gene mutations, and it is
      clinically characterized by an eyelid malformation associated (type I) or not
      (type II) with premature ovarian failure (POF). Functional study of novel
      mutations is especially critical for female patients, as it may allow the
      prediction of infertility and early planning of an appropriate therapy. METHODS:
      A clinical and molecular genetic investigation was performed in all members of a
      Chinese family with BPES. Genomic DNA was extracted, and the FOXL2 coding region
      was sequenced. Subcellular localization was performed by confocal microscopy.
      Transactivation studies were performed by real-time PCR, dual luciferase reporter
      assays and electrophoretic mobility shift assays. RESULTS: A novel deletion
      mutation (C.634_641 del, CCCATGC) between the forkhead domain and the polyalanine
      domain was found, resulting in a frameshift mutation and a truncated protein.
      Functional studies showed a strong cytoplasmic mislocalization and abnormal
      transactivation activity, implying a type I kind mutation with a large chance of
      infertility. CONCLUSION: This study identifies that this mutation indicates the
      probability of developing into POF and shows the importance and necessity of
      early recognition of BPES type through mutation testing for female patients.
      Prompt personalized therapy and follow-up is of great clinical significance for
      female patients carrying this kind of mutation.

PMID- 29339662
TI  - Cytogenetic Characterization of Eight Odonata Species Originating from the
      Curonian Spit (the Baltic Sea, Russia) Using C-Banding and FISH with 18S rDNA and
      Telomeric (TTAGG)n Probes.
AB  - We studied the karyotypes of 8 dragonfly species originating from the Curonian
      Spit (the Baltic Sea, Russia) using C-banding and FISH with 18S rDNA and "insect"
      telomeric (TTAGG)n probes. Our results show that Leucorrhinia rubicunda,
      Libellula depressa, L. quadrimaculata, Orthetrum cancellatum, Sympetrum danae,
      and S. vulgatum from the family Libellulidae, as well as Cordulia aenea and
      Epitheca bimaculata from the family Corduliidae share 2n = 25 (24 + X) in males,
      with a minute pair of m-chromosomes being present in every karyotype except for
      that of C. aenea. Major rDNA clusters are located on one of the large pairs of
      autosomes in all the species. No hybridization signals were obtained by FISH with
      the (TTAGG)n probe in the examined species with the only exception of S.
      vulgatum. In this species, clear signals were detected at the ends of almost all
      chromosomes. This finding raises the possibility that in Odonata the canonical
      "insect" (TTAGG)n telomeric repeat is in fact present but in very low copy number
      and is consequently difficult to detect by in situ hybridization. We conclude
      that more work needs to be done to answer questions about the organization of
      telomeres in this very ancient and thus phylogenetically important insect order.

PMID- 29339663
TI  - Evaluation of Magnetic Resonance Imaging/Ultrasound-Fusion Biopsy in Patients
      with Low-Risk Prostate Cancer Under Active Surveillance Undergoing Surveillance
      Biopsy.
AB  - INTRODUCTION: Targeted biopsy of tumour-suspicious lesions detected in
      multiparametric magnetic resonance imaging (mpMRI) plays an increasing role in
      the active surveillance (AS) of patients with low-risk prostate cancer (PCa). The
      aim of this study was to compare MRI/ultrasound-fusion biopsy (fusPbx) with
      systematic biopsy (sysPbx) in patients undergoing biopsy for AS. METHODS:
      Patients undergoing mpMRI and transperineal fusPbx combined with transrectal
      sysPbx (comPbx) as surveillance biopsy were investigated. The detection of
      Gleason score upgrading and reclassification according to Prostate Cancer
      Research International Active Surveillance criteria were evaluated. RESULTS:
      Eighty-three patients were enrolled. PCa upgrading was detected in 39% by fusPbx
      and in 37% by sysPbx (p = 1.0). The percentage of patients who were reclassified
      in fusPbx and sysPbx (p = 0.45) were 64 and 59% respectively. ComPbx detected
      more frequently tumour upgrading than fusPbx (71 vs. 64%, p = 0.016) and sysPbx
      (71 vs. 59%, p < 0.001) and more patients had to be reclassified after comPbx
      than after fusPbx or sysPbx alone. CONCLUSIONS: The combination of fusPbx and
      sysPbx outperforms both modalities alone with regard to the detection of
      upgrading and reclassification in patients under AS. Because a high missing rate
      of significant PCa still exists in both biopsy modalities, a combination of
      fusPbx and sysPbx should be recommended in these patients.

PMID- 29339664
TI  - Cenesthopathy and Subjective Cognitive Complaints: An Exploratory Study in
      Schizophrenia.
AB  - BACKGROUND/AIMS: Cenesthopathy is mainly associated with schizophrenia; however,
      its neurobiological basis is nowadays unclear. The general objective was to
      explore clinical correlates of cenesthopathy and subjective cognitive complaints
      in schizophrenia. METHODS: Participants (n = 30) meeting DSM-IV criteria for
      psychotic disorder were recruited from a psychiatry unit and assessed with:
      Association for Methodology and Documentation in Psychiatry (AMDP) system,
      Positive and Negative Syndrome Scale, Frankfurt Complaint Questionnaire (FCQ),
      and the Bonn Scale for the Assessment of Basic Symptoms (BSABS). For quantitative
      variables, means and Spearman correlation coefficients were calculated. Linear
      regression following backward method and principal component analysis with
      varimax rotation were used. RESULTS: 83.3% of subjects (73.3% male, mean age,
      31.5 years) presented any type of cenesthopathy; all types of cenesthetic basic
      symptoms were found. Cenesthetic basic symptoms significantly correlated with the
      AMDP category "fear and anancasm," FCQ total score, and BSABS cognitive thought
      disturbances. In the regression analysis only 1 predictor, cognitive thought
      disturbances, entered the model. In the principal component analysis, a main
      component which accounted for 22.69% of the variance was found. CONCLUSIONS:
      Cenesthopathy, as assessed with the Bonn Scale (BSABS), is mainly associated with
      cog-nitive abnormalities including disturbances of thought initiative and mental
      intentionality, of receptive speech, and subjective retardation or pressure of
      thoughts.

PMID- 29339665
TI  - Novel Translational Research Methodology and the Prospect to a Better
      Understanding of Neurodegenerative Disease.

PMID- 29339666
TI  - Preventive Cold Acclimation Augments the Reparative Function of Endothelial
      Progenitor Cells in Mice.
AB  - BACKGROUND/AIMS: Chronic cold exposure may increase energy expenditure and
      contribute to counteracting obesity, an important risk factor for
      cerebrocardiovascular diseases. This study sought to evaluate whether preventive
      cold acclimation before ischemia onset might be a promising option for preventing
      cerebral ischemic injury. METHODS: After a 14-day cold acclimation period, young
      and aged mice were subjected to permanent cerebral ischemia, and histological
      analyses and behavioral tests were performed. Mouse endothelial progenitor cells
      (EPCs) were isolated, their function and number were determined, and the effects
      of EPC transplantation on cerebral ischemic injury were investigated. RESULTS:
      Preventive cold acclimation before ischemia onset increased EPC function,
      promoted ischemic brain angiogenesis, protected against cerebral ischemic injury,
      and improved long-term stroke outcomes in young mice. In addition, transplanted
      EPCs from cold-exposed mice had a greater ability to reduce cerebral ischemic
      injury and promote local angiogenesis compared to those from control mice, and
      EPCs from donor animals could integrate into the recipient ischemic murine brain.
      Furthermore, transplanted EPCs might exert paracrine effects on cerebral ischemic
      injury, which could be improved by preventive cold acclimation. Moreover,
      preventive cold acclimation could also enhance EPC function, promote local
      angiogenesis, and protect against cerebral ischemic injury in aged mice.
      CONCLUSIONS: Preventive cold acclimation before ischemia onset improved long-term
      stroke outcomes in mice at least in part via promoting the reparative function of
      EPC. Our findings imply that a variable indoor environment with frequent cold
      exposure might benefit individuals at high risk for stroke.

PMID- 29339667
TI  - Improving Laboratory Assessment in Disorders of Sex Development through a
      Multidisciplinary Network.
AB  - The aim of the European Reference Network for Rare Endocrine Disorders (Endo-ERN)
      is to ensure equal access to high-quality care for all those affected by a rare
      endocrine condition across Europe, such as a disorder/difference of sex
      development (DSD), both for children and adults. Although differences in
      resources, health care systems, and health insurances between the European
      countries are challenging and require political action, a European laboratory
      network within Endo-ERN could improve the diagnostic process in individuals with
      DSD, building on the work done by previous European collaborations such as the
      COST action DSDnet. In close collaboration, clinicians and laboratory specialists
      must make every effort to standardize diagnostic protocols, achieve necessary
      harmonization of various laboratory tests, e.g., the hCG stimulation test, and
      implement an external quality control system. This should ideally result in
      comparable quality across the network centers allowing the sharing of reference
      values. This would not only improve patient care but also greatly facilitate
      research.

PMID- 29339668
TI  - Proinflammatory Cytokines and Oxidative Stress Decrease the Transport of Dopamine
      Precursor Tyrosine in Human Fibroblasts.
AB  - BACKGROUND: Proinflammatory cytokines and oxidative stress responses have been
      extensively implicated in the pathophysiology of neuropsychiatric disorders over
      the past 2 decades. Moreover, disturbed transport of the dopamine precursor
      (i.e., the amino acid tyrosine) has been demonstrated, in different studies,
      across fibroblast cell membranes obtained from neuropsychiatric patients.
      However, the role and influences of proinflammatory cytokines and oxidative
      stress, and the reasons for disturbed tyrosine transport in neuropsychiatric
      disorders, are still not evaluated. AIMS: The present study aimed to assess the
      role of proinflammatory cytokines and oxidative stress, indicated in many
      neuropsychiatric disorders, in tyrosine transportation, by using human skin
      derived fibroblasts. METHODS: Fibroblasts obtained from a healthy control were
      used in this study. Fibroblasts were treated with proinflammatory cytokines (IL
      1beta, IFN-gamma, IL-6, TNF-alpha), their combinations, and oxidative stress,
      optimized for concentrations and incubation time, to analyze the uptake of 14C
      tyrosine compared to untreated controls. RESULTS AND CONCLUSION: This study
      demonstrates that proinflammatory cytokines and oxidative stress decrease the
      transport of tyrosine (47% and 33%, respectively), which can alter dopamine
      synthesis. The functionality of the tyrosine transporter could be a new potential
      biomarker to target for discovering new drugs to counteract the effects of
      proinflammatory cytokines and oxidative stress in the pathophysiology of
      neuropsychiatric disorders.

PMID- 29339669
TI  - Signalling molecules in jaw bones and gingival tissues of patients with Class II
      and Class III dentofacial deformities.
AB  - OBJECTIVES: To detect signalling molecule specificities in jaw bone growth zones
      in skeletal class II and class III patients and compare them to those of a
      control group. MATERIAL AND METHODS: Twenty skeletal Class II and 20 skeletal
      Class III patients who underwent orthognathic surgery treatment were in the study
      group and five skeletal Class I patients who had impacted third molars extracted
      were in the control group. During the orthognathic surgery, tissue samples were
      taken from the tuber maxillae, ramus mandibulae anterior and posterior part
      together with mucosa from the gingival transitory fold in the second molar region
      of the lower jaw. The samples were stained to detect TGF-beta, BMP2/4, FGFR1,
      VEGF, OC, OP and MMP2 expression. The distributions of these factors were
      assessed semiquantitatively. RESULTS: We observed significant expression of TGF
      beta, BMP2/4, OC and OP in the bone tissue of the study group. FGFR1 expression
      was more pronounced only in mucosa. VEGF and MMP2 were found only in some tissue
      samples. More apoptotic cells were observed in the bone tissue and soft tissue of
      the control patients than in those of the skeletal Class II and Class III
      patients, in which apoptotic cell frequencies were relatively equal. CONCLUSION:
      From bone tissue in tuber maxillae region the greater TGF-beta and BMP2/4
      expression is seen in Class III and control groups, comparing to Class II. In
      ramus mandibulae anterior part the expression of significant factors in bone
      tissue growth (TGF-beta un BMP2/4) is higher in the control group and Class II
      patients, while in ramus mandibulae posterior part higher expression of TGF-beta
      and BMP2/4 is in Class III patients, comparing to Class II, which indicates to a
      preserved growth potential in these jaw bone regions. More active bone
      extracellular matrix protein (osteocalcin and osteopontin) expression in tuber
      maxillae region both in class II and class III patient groups and different
      expression in ramus mandibulae anterior part, prove to the bone mineralization
      and metabolism activity changes, which, perhaps, characterize just these
      dentofacial deformations.

PMID- 29339670
TI  - Family history and risk factors for cleft lip and palate patients and their
      associated anomalies.
AB  - BACKGROUND AND AIMS: Several environmental and genetic issues have been suspected
      as risk factors for oral clefts; and many studies have been conducted in this
      regard; however, large socioeconomic impacts of cleft lip and or palate (CL/P)
      justifies the need for further multifactorial researches. Current study aimed to
      assess parental risk factors for CL/P and its associated malformations. MATERIAL
      AND METHODS: Hospital records of 187 consecutive syndromic and non-syndromic
      children with cleft lip and or palate (103 boys and 84 girls) with a mean age of
      1.7 (SD 2.2) years and 190 consecutive non-cleft children (103 boys and 87 girls)
      with a mean age of 2.8 (SD 2.2) years formed this study. Parental risk factors
      and abnormalities and physical problems and anomalies were evaluated in all
      subjects. RESULTS: Family history of clefts (OR 7.4; 95% CI), folic acid
      consumption (OR 7.3; 95% CI) and consanguineous marriage (OR 3.2; 95% CI) were
      quite strongly associated with increased risk of CL/P. In addition, all
      congenital abnormalities and physical problems had significantly higher incidence
      in CL/P patients. CONCLUSIONS: The findings of this study suggest that expecting
      mothers of consanguineous marriage and families with a history of CL/P should be
      extra cautious about the occurrence of CL/P.

PMID- 29339671
TI  - Psychosocial factors correlated with children's dental anxiety.
AB  - Authors developed an idea of seven blocks with different psychosocial factors
      that could correlate with children's dental anxiety and explain its variance. Aim
      of the study was to evaluate correlation between psychosocial factors and
      children's dental anxiety. Totally, 240 randomly selected children (mean age
      M=7.96, SD=2.61, range 4 to 12) and their parents took part in the study. Parents
      evaluated their own (MDAS) and their children's anxiety (CFSS-DS). Psychosocial
      factors were evaluated by a large questionnaire, developed for this study. Dental
      status was fixed and child's behavior in dental setting was evaluated with
      Frankl's scale. Pearson's correlation of CDA with all variables and stepwise
      linear regression with the correlating variables within the seven psychosocial
      factor blocks was performed. Dental experience and attitude factors (crying at
      dentist and dental treatment with difficulties) as well as Children's personality
      and behavior factors (general anxiety and children's behavior at dentist) gave
      the most effect on CDA, totally explaining 56% and 54% of variance, respectively.
      Children's medical experience and attitude factors (anxiety and caution towards
      doctors) as well as Parental/information factors (parental dental anxiety,
      promising prizes before treatment) explained 34% and 31% of CDA variance,
      respectively. Socio-economic factors (number of children and mother's age)
      explained 15%, but oral care habits and attitude (brushing as obligation) - 14%
      of CDA variance. Family distress factors had no correlation with CDA and were
      excluded of further analysis. Children's dental anxiety variance is at best
      explained by Child's dental experience and attitude factors and Child's
      personality and behavior factors.

PMID- 29339672
TI  - Serum and salivary lactate dehydrogenase levels as biomarkers of tissue damage
      among cigarette smokers. A biochemical study.
AB  - OBJECTIVE: To estimate the serum and salivary lactate dehydrogenase levels in
      cigarette smokers and non-smokers. MATERIALS AND METHODS: In this study lactate
      dehydrogenase levels were estimated in 30 healthy individuals with no tobacco
      related habits and in 30 patients with history of smoking cigarettes for a
      minimum of 2 years using Spectrophotometry. RESULTS: The mean values for serum
      and salivary lactate dehydrogenase levels were higher in cigarette smokers when
      compared to non-smokers. Serum lactate dehydrogenase levels on comparison between
      the groups was statistically significant (p=0.04). The values of salivary lactate
      dehydrogenase levels between the groups was highly significant (p<0.001).
      CONCLUSION: Cigarette smoking leads to an increase in serum as well as salivary
      Lactate dehydrogenase levels as indicator of tissue damage in the oral cavity.
      The present study indicates saliva as a better test medium than serum in
      determination of lactate dehydrogenase levels.

PMID- 29339673
TI  - Histopathological and microradiological features of peri-implantitis. A case
      report.
AB  - AIM: The aim of this study was to describe the histological characteristics of a
      peri-implantitis case in the anterior maxilla. CASE REPORT: A dental implant
      inserted in the missing upper right lateral incisor region has been removed with
      its adjacent tissues. The samples were placed in 4% formalin for 10 days and,
      were embedded in methacrylate prior to sawing and grinding. The samples were
      processed with Donath's sawing and grinding technique, stained with toluidine
      blue and mounted on high-sensitivity plates for histology and microradiography.
      The structure of the connective tissue revealed that there was a lack of collagen
      fibers running parallel to the implant surface. The connective tissue showed a
      loose granulation tissue with medium-density lymphocyte infiltration and
      neutrophilic leukocytes. In addition to the collagen loss in the infiltrated
      tissue, an excessive bone resorption was present. Peripherally, the light
      microscopy showed the osteoclasts and their adhesive apparatus which promote bone
      resorption. CONCLUSION: With the increasing number of implants being placed, peri
      implantitis has become much more prevalent. Every additional study focusing on
      the characteristics of peri-implantitis would be beneficial to gain an
      understanding of bone and soft tissue behavior around the implant and could help
      to develop appropriate therapeutic approaches for peri-implant disease.

PMID- 29339674
TI  - Relation between high serum hepcidin-25 level and subclinical atherosclerosis and
      cardiovascular mortality in hemodialysis patients.
AB  - OBJECTIVE: In hemodialysis (HD) patients, cardiovascular disease (CVD) is the
      major cause of mortality and morbidity. In atherosclerotic diseases, iron gets
      accumulated in the arterial wall. Hepcidin is an important hormone in iron
      metabolism. Furthermore, hepcidin is associated with atherosclerotic disease.
      Therefore, this study aims to investigate the relation of serum hepcidin-25 (SH
      25) and sub-clinic atherosclerosis measured by carotid intima-media thickness
      (CIMT) and mortality in HD patients. METHODS: We enrolled 82 HD patients in a
      cross-control study. We measured SH-25 using ELISA kit and CIMT using high
      resolution real-time ultrasonography. After 4 years of first assessment, we
      investigated the relation between all-cause and cardiovascular mortality and SH
      25 and CIMT. RESULTS: Two patients were excluded because of renal
      transplantation. The survivors were younger (53.7+/-15.1 vs. 65.2+/-15.5; p<0.05)
      and CIMT was lower (0.83+/-0.2 vs. 0.95+/-0.2; p<0.05); however, there was no
      significant difference in SH-25 levels between the groups (29.1+/-13 vs. 32.4+/
      22.4; p=0.767). The patients who died of CVD were significantly older (63.7+/
      16.1 vs. 53.7+/-15.1; p<0.05) and had significantly higher CIMT (0.94+/-0.2 vs.
      83+/-0.2; p<0.05). The SH-25 levels were statistically significantly higher in
      patients who died of CVD (40.3+/-25 vs. 29.1+/-13; p<0.05). Linear regression
      analysis showed a positive correlation between CIMT and SH-25 in the study
      population and in those who died from CVD (r=0.41; p<0.05 and r=0.606; p<0.05,
      respectively). CONCLUSION: This study suggests that hepcidin is effective in
      cardiovascular mortality and pathophysiology of subclinical atherosclerosis in HD
      patients.

PMID- 29339675
TI  - Association of serum prolidase activity in patients with isolated coronary artery
      ectasia.
AB  - OBJECTIVE: Coronary artery ectasia (CAE) is defined as an angiographic
      enlargement of a portion of the coronary artery between 1.5 and 2 times the
      diameter of the adjacent normal coronary artery. It has been demonstrated that
      increased serum prolidase activity (SPA) is associated with increased collagen
      turnover. We aimed to analyze the relationship between CAE and serum SPA levels.
      METHODS: This study used a prospective case protocol design. A total of 40
      consecutive patients with isolated right CAE and normal coronary arteries (23
      men, 17 women; mean age, 62.4+/-10.8 years) were evaluated. The control group
      included the same number of consecutive patients with angiographically normal
      coronary arteries (20 men, 20 women; mean age, 63.8+/-11.1 years). Clinical
      characteristics, laboratory results, cardiovascular risk factors, and medication
      use were recorded. SPA was measured using a spectrophotometer. Student's t-test,
      Mann-Whitney U test, chi-square test, Pearson's and Spearman's correlations,
      logistic regression analysis, and ROC curve analysis were used for statistical
      analysis. RESULTS: SPA was significantly higher in the CAE group compared with
      the control group (1635.2+/-492.0 U/L and 986.2+/-422.3 U/L, respectively;
      p<0.001). The relationship of SPA with CAE proved to be significant (r=0.512;
      p<0.001). SPA also served as an independent predictor of CAE (OR=1.003; 95% CI,
      1.001-1.005; p=0.002). The SPA value of 1170 U/L was predictive of CAE, with a
      sensitivity of 85% and specificity of 60% (AUC=0.854; 95% CI, 0.763-0.944;
      p<0.001). CONCLUSION: The activity of this enzyme was significantly correlated
      with CAE.

PMID- 29339676
TI  - Electrical and histological remodeling of the pulmonary vein in 2K1C hypertensive
      rats: Indication of initiation and maintenance of atrial fibrillation.
AB  - OBJECTIVE: Hypertension is a significant risk factor for atrial fibrillation
      (AF). The role of pulmonary vein (PV) remodeling in the mechanistic association
      between hypertension and AF is not definitive. In this study, we aimed to
      identify changes in the electrophysiology and histology in PVs in two-kidney, one
      clip (2K1C) hypertensive rats. METHODS: Fifty male Sprague-Dawley rats were
      classified into the 2K1C and sham-operated groups. The systolic blood pressure
      was measured every 2 weeks. The left atrial diameter was measured by
      transthoracic echocardiography. Left superior PV (LSPV) and left atrial (LA)
      fibrosis was evaluated by Masson's trichrome staining. The expression of fibrosis
      markers [angiotensin II (Ang II), transforming growth factor-beta1 (TGF-beta1),
      matrix metalloproteinase-2 (MMP-2), and collagen I (Col I)] and ion channels
      [Kir2.1, Kir2.3, Cav1.2, and Nav1.5] in LSVP was quantified by western blot.
      Conventional microelectrodes were used to record the action potential duration at
      90% repolarization (APD90) and effective refractory period (ERP) in isolated LA.
      RESULTS: At 4 months, the 2K1C hypertensive rats developed LA dilation. Col
      deposition in LSPV and left atrium and expression of TGF-beta1, MMP-2, and Col I
      in LSPV were significantly increased in 2K1C hypertensive rats. In addition,
      hypertension reduced the expression of Nav1.5 and Kir2.1, although there were no
      significant differences in APD90; ERP; and expression of Ang II, Kir2.3, and
      Cav1.2 between the two groups. CONCLUSION: Hypertension may lead to changes in
      the electrophysiology and histology of rats PVs, which is characterized by
      significant reduction in the expression of Nav1.5 and Kir2.1 and increase in
      interstitial fibrosis. These observations may clarify the role of PVs in the
      mechanistic association between hypertension and AF.

PMID- 29339677
TI  - Acute myocardial infarction shortly after valve-in-valve transcatheter aortic
      valve implantation successfully managedwith challenging percutaneous coronary
      intervention.
AB  - In recent years, transcatheter aortic valve implantation (TAVI) has been
      considered a novel option for the management of surgically high-risk patients
      requiring aortic valve replacement. Presently described is a case of acute
      coronary syndrome (ACS) managed with a challenging primary percutaneous coronary
      intervention (PCI) shortly after a valve-in-valve TAVI intervention. This case
      highlights 2 important issues: PCI may be an option for the management of
      coronary heart disease in patients after TAVI even in the setting of demanding
      features associated with coronary osteal engagement, and secondly, TAVI may serve
      as a potential risk factor for future coronary ischemic syndromes, largely due to
      its potential adverse effects on coronary flow dynamics, etc. However, the latter
      notion is quite speculative, and should be tested in further studies.

PMID- 29339678
TI  - Endarteritis of coarctation of the aorta diagnosed with PET-CT.
AB  - Infective endocarditis (IE) is an infectious disease that affects the endothelium
      of the large intrathoracic vessels, heart valves, and intra-cardiac foreign body
      material. A 20-year-old woman was admitted to the cardiology department with
      complaints of fever and palpitations. Transthoracic echocardiography revealed a
      bicuspid aortic valve, aortic root enlargement, and aortic coarctation.
      Transesophageal echocardiography revealed a bicuspid aortic valve, but there was
      no vegetation. Methicillin-sensitive Staphylococcus aureus was identified on a
      blood culture. 18F-fluorodeoxyglucose positron emission tomography-computed
      tomography (18F-FDG PET-CT) revealed increased intensive glucose uptake on the
      dilated aortic segment adjacent to the distal coarctation zone. Several reports
      have shown promising results for radio-labelled white blood cell single-photon
      emission computed tomography and 18F-FDG PET-CT imaging in IE. To our knowledge,
      this is the first described case in which PET-CT revealed endarteritis of the
      descending aorta in a patient without prosthetic material.

PMID- 29339679
TI  - A rare complication in a patient taking rivaroxaban: Alveolar hemorrhage.
AB  - Alveolar hemorrhage (AH) is a heterogeneous clinical syndrome with a high
      mortality rate that is characterized by extensive bleeding into the alveolar
      spaces. AH usually develops secondary to immunological disease and, less
      frequently, to drug use. Presently described is the case of an 86-year-old woman
      with AH who had been using rivaroxaban for 6 months.

PMID- 29339680
TI  - Case Image: Percutaneous approach to giant coronary artery aneurysm: successful
      implantation of covered stent graft.

PMID- 29339681
TI  - Case Image: Superdominant right coronary artery and left anterior descending
      artery arising from the right coronary sinus: a rare coronary artery anomaly.

PMID- 29339682
TI  - Case Image: A rare angiographic image of Vieussens' arterial ring associated with
      coronary to pulmonary artery fistula.

PMID- 29339683
TI  - Case Image: Double aortic arch presenting with respiratory disorders.

PMID- 29339684
TI  - [2017 ESC focused update on dual antiplatelet therapy in coronary artery disease
      developed in collaboration with EACTS: What is new?]

PMID- 29339685
TI  - Intra-aortic balloon pump use in acute coronary syndrome: One size does not fit
      all!

PMID- 29339686
TI  - Clinical characteristics and outcomes of acute coronary syndrome patients with
      intra-aortic balloon pump inserted in intensive cardiac care unit of a tertiary
      clinic.
AB  - OBJECTIVE: An intra-aortic balloon pump (IABP) is a mechanical support device
      that is used in addition to pharmacological treatment of the failing heart in
      intensive cardiac care unit (ICCU) patients. In the literature, there are limited
      data regarding the clinical characteristics and in-hospital outcomes of acute
      coronary syndrome patients in Turkey who had an IABP inserted during their ICCU
      stay. This study is an analysis of the clinical characteristics and outcomes of
      these acute coronary syndrome patients. METHODS: The data of patients who were
      admitted to the ICCU between September 2014 and March 2017 were analyzed
      retrospectively. The data were retrieved from the ICCU electronic database of the
      clinic. A total of 142 patients treated with IABP were evaluated in the study.
      All of the patients were in cardiogenic shock following percutaneous coronary
      intervention, at the time of IABP insertion. RESULTS: The mean age of the
      patients was 63.0+/-9.7 years and 66.2% were male. In-hospital mortality rate of
      the study population was 54.9%. The patients were divided into 2 groups,
      consisting of survivors and non-survivors of their hospitalization period.
      Multivariate analysis after adjustment for the parameters in univariate analysis
      revealed that ejection fraction, Thrombolysis in Myocardial Infarction flow score
      of <=2 after the intervention, chronic renal failure, and serum lactate and
      glucose levels were independent predictors of in-hospital mortality. CONCLUSION:
      The mortality rate remains high despite IABP support in patients with acute
      coronary syndrome. Patients who are identified as having a greater risk of
      mortality according to admission parameters should be further treated with other
      mechanical circulatory support devices.

PMID- 29339687
TI  - Subclinical left ventricular systolic dysfunction in patients with severe aortic
      stenosis: A speckle-tracking echocardiography study.
AB  - OBJECTIVE: In patients with aortic stenosis (AS), the left ventricular (LV)
      geometry changes due to the increased LV afterload. However, subclinical
      myocardial dysfunction can develop despite a normal LV ejection fraction (EF).
      This study was an investigation of subclinical LV systolic dysfunction in
      patients with severe AS with a normal LV EF using a strain imaging method,
      speckle-tracking echocardiography (STE), and an evaluation of its correlation
      with novel indices to assess the severity of AS. METHODS: A total of 45
      asymptomatic patients with severe AS and 25 age- and sex-matched controls without
      any cardiac disease and with preserved LV EF (EF >=60%) were studied. In addition
      to performing conventional echocardiography and STE-based strain imaging, novel
      indices (energy loss index [ELI], valvulo-arterial impedance, systemic arterial
      compliance) were also measured. RESULTS: The LV EF, and the LV end-diastolic and
      end-systolic diameters were similar in the 2 groups. The LV longitudinal peak
      systolic strain (10.66+/-1.15% to 19.66+/-2.62%; p=0.0001) and strain rate
      (0.32+/-0.07 s-1 to 1.85+/-0.32 s-1; p=0.0001) were significantly impaired in the
      study patients compared to the controls, demonstrating subclinical ventricular
      systolic dysfunction. A significant positive correlation was observed between the
      ELI and the LV strain/strain rate (r=0.45, p=0.002; r=0.55, p=0.0001,
      respectively). CONCLUSION: Patients with severe AS develop subclinical LV
      systolic dysfunction, despite a preserved EF. Novel strain imaging-based
      echocardiographic techniques may provide additional data that can detect early
      myocardial systolic deterioration in these patients.

PMID- 29339688
TI  - Choice of treatment based on Turkish hypertension consensus report: Do we follow
      the recommendations?
AB  - OBJECTIVE: The aim of this study was to determine how often the recommendations
      of the Turkish Hypertension Consensus Report are followed, and to draw attention
      to the report. METHODS: The demographic information of 1000 patients diagnosed
      with hypertension and the details of the antihypertensive medications prescribed
      at the outpatient service of a tertiary care hospital were recorded, and the data
      were compared with the recommendations of the report. RESULTS: The mean age of
      the patients was 62+/-11 years. In all, 623 (62.3%) of the 1000 patients were
      women, and 377 (37.7%) were men. A combination of an angiotensin II receptor
      blocker (ARB) and a diuretic was the most frequently observed prescription. A
      diuretic was the most used antihypertensive drug (58.7%), followed by an ARB
      (48.8%). However, as a monotherapy, a calcium channel blocker (CCB) was the most
      commonly used antihypertensive drug (19.2%). The most frequently used
      antihypertensive drug group in older patients was diuretics (63.6%), as proposed
      in the report. Beta blockers (49.1%) were used more often than expected. For the
      diabetic group also, a diuretic (60.7%) was the most frequently used
      antihypertensive drug, followed by an ARB (51.1%) and a CCB (45.2%). Angiotensin
      converting enzyme (ACE) inhibitors (34.6%) were the fifth most preferred
      antihypertensive drug class. However, when ACE inhibitors and ARBs were
      considered as a single group, known as renin-angiotensin system (RAS) blockers,
      these RAS blockers were the most prescribed antihypertensive drug class, followed
      by diuretics. In the group of patients with coronary artery disease, treatment
      was found to be generally consistent with the report, but the use of diuretics
      was greater than expected. Lastly, 124 of 160 patients who had chronic kidney
      disease were given RAS blocker therapy, which was in line with the consensus
      report recommendations. CONCLUSION: Antihypertensive therapies were
      individualized, as suggested by the consensus report. However, there are
      proposals still to be considered in special patient groups.

PMID- 29339689
TI  - Atherogenic index of plasma as a cardiovascular risk marker in manic, depressive,
      and euthymic stages of bipolar disorder.
AB  - OBJECTIVE: Individuals with bipolar disorder (BD) frequently suffer from
      cardiovascular disease (CVD), and it is a leading cause of mortality. Clinicians
      use routine laboratory tests, including a lipid profile, to predict
      cardiovascular risk. In addition, a particular lipid ratio, the atherogenic index
      of plasma (AIP), is a sensitive, new parameter that can be used to assess
      highrisk groups. To our knowledge, this is the first study evaluating
      cardiovascular risk via AIP in different stages of BD. METHODS: The study group
      consisted of male patients with BD who were in a manic, depressive, or euthymic
      state, and age- and gender-matched healthy controls. Lipid profiles were analyzed
      and the AIP parameter of logarithm of triglyceride (TG) / high-density
      lipoprotein cholesterol (HDLc) was calculated for all of the participants. The
      significance level was set at p<0.05. RESULTS: A total of 44 BD patients
      experiencing a manic episode, 35 depressive BD patients, 42 euthymic patients,
      and 41 healthy controls matched for age, gender, and smoking status were enrolled
      in the study. The AIP level was significantly different between groups (p=0.009).
      Pairwise comparisons of the groups revealed that the AIP level of depressive
      patients was significantly higher than that of the manic, euthymic, and control
      groups (p=0.013, p=0.048, and p=0.021, respectively). The AIP level was
      positively correlated with body mass index, waist circumference, metabolic
      syndrome, total cholesterol, low-density lipoprotein, and triglyceride level, and
      was negatively correlated with the HDLc level. CONCLUSION: In this study, male BD
      patients in a depressive episode demonstrated an increase in cardiovascular risk.
      The significant correlations between AIP and other conventional cardiovascular
      risk factors indicate that AIP may be more useful to identify individuals with BD
      at high risk for CVD than absolute lipid parameters.

PMID- 29339690
TI  - The rationale and design of the national peripartum cardiomyopathy registries in
      Turkey: The ARTEMIS-I and ARTEMIS-II studies.
AB  - OBJECTIVE: Peripartum cardiomyopathy (PPCM) is left ventricular (LV) systolic
      dysfunction with an ejection fraction of <=45% occurring in the later stages of
      pregnancy or soon after delivery. Although various risk factors have been
      identified, the exact cause of the disease is unknown. Unlike most countries in
      the European region, Turkey has yet to determine the current PPCM burden. A
      registry for this purpose does not exist. To close this gap, the A RegisTry of
      pEripartuM cardIomyopathy in Turkish patientS (ARTEMIS-I and ARTEMIS-II), was
      planned and endorsed by the Turkish Society of Cardiology. The aim of this
      manuscript is to describe the rationale and design of the ARTEMIS-I and ARTEMIS
      II registries. METHODS: ARTEMIS was designed to be the nationwide PPCM registry
      of Turkey, with the goal of identifying problems and opportunities while
      improving quality and consistency in the medical care of PPCM patients. A second
      goal is to determine the clinical characteristics pertinent to patients in this
      region. The ARTEMIS registry will consist of 2 arms. All secondary and tertiary
      cardiology centers have been electronically invited to participate in ARTEMIS-I,
      which will be conducted to assess the current standard of care and outcome
      measures. Centers will be asked to enroll PPCM patients admitted to their clinic
      in last 5 years retrospectively. Eligibility criteria will consist of pregnant or
      early postpartum woman without a previous history of heart failure (HF) or known
      pathology associated with HF, LV ejection fraction <=45%, and exclusion of other
      causes of LV systolic dysfunction. ARTEMIS-II will consist of the prospective
      enrollment of patients. CONCLUSION: The nationwide PPCM registries, ARTEMIS-I and
      ARTEMIS-II, are designed to determine the current status of medical care, provide
      insights into nature of the disease, and suggest solutions on how to improve care
      and outcomes in these patients.

PMID- 29339691
TI  - Rationale, design, and methodology of the Evaluation of Perceptions, Knowledge,
      and Compliance with the Guidelines in Real Life Practice: A Survey on the Under
      treatment of Hypercholesterolemia.
AB  - OBJECTIVE: A wide gap exists between dyslipidemia guidelines and their
      implementation in the real world, which is primarily attributed to physician and
      patient compliance. The aim of this study is to determine physician and patient
      adherence to dyslipidemia guidelines and various influential factors. METHODS:
      The Evaluation of Perceptions, Knowledge, and Compliance with the Guidelines in
      Real Life Practice: A Survey on the Under-treatment of Hypercholesterolemia
      (EPHESUS) trial (ClinicalTrials.gov number NCT02608645) will be an observational,
      multicenter, non-interventional study. The study targets enrollment of 2000
      patients from 50 locations across Turkey. All of the data will be collected in a
      single visit and current clinical practice will be evaluated. A cross-sectional
      survey of public perception and knowledge of cholesterol treatment among Turkish
      adults will be performed. All consecutive patients admitted to cardiology clinics
      who are in the secondary prevention group (coronary heart disease, peripheral
      artery disease, atherosclerotic cerebrovascular disease) and who are in the high
      risk primary prevention group (type 2 diabetes mellitus with no prior known
      coronary heart disease; patients who had markedly elevated single risk factors,
      in particular, cholesterol >8 mmol/L [>310 mg/dL], blood pressure >=180/110 mmHg,
      a calculated Systematic Coronary Risk Evaluation [SCORE] >=5%, or <10% 10-year
      risk of fatal cardiovascular disease) will be included. Demographic, lifestyle,
      medical, and therapeutic data will be collected with a survey designed for the
      study. CONCLUSION: The EPHESUS registry will be the largest study conducted in
      Turkey evaluating the adherence to dyslipidemia guidelines both in secondary and
      high-risk primary prevention patients.

PMID- 29339692
TI  - Transvenous extraction of a 26-year-old Accufix atrial lead using TightRail
      rotating dilator sheath.
AB  - With the increasing number of implanted pacemakers and implantable cardioverter
      defibrillators, removal is required more frequently. Presently described is the
      transvenous extraction of a 26-year-old Accufix atrial lead using a mechanical
      dilator sheath. A 50-year-old male patient was admitted to the clinic with a
      pacemaker pocket infection. The atrial lead was an Accufix Bipolar J-Atrial
      active fixation lead, a model that was recalled in 1994, after reports of 2
      deaths and 2 nonfatal injuries related to protrusion of the J retention wire.
      Both the atrial and ventricular leads were extracted using a mechanical dilator
      sheath. The Pacemaker Lead Extraction with the Excimer Sheath (PLEXES) Trial
      reported that of the 57 Accufix leads randomized to a non-laser approach, only
      47% were removed successfully, compared with 96% of laser-randomized cases. Since
      laser sheaths are not available in Turkey, use of a mechanical dilator sheath was
      required. To our knowledge, this is the oldest Accufix lead extracted with a non
      laser sheath. During the extraction of the ventricular lead, the tip of the lead
      broke off inside the right ventricle and the residual part was left inside the
      heart. During 3 months of follow-up, no signs of infection or any other
      undesirable events were encountered.

PMID- 29339693
TI  - Simultaneous total occlusion of two coronary arteries associated with use of
      drospirenone-ethinyl estradiol (oral contraceptive).
AB  - Although the use of oral contraceptives is associated with an increased risk of
      venous thromboembolic disease, the risk of myocardial infarction (MI) is unclear.
      A new, third-generation contraceptive agent, drospirenone-ethinyl estradiol,
      which contains less estrogen and a new progestogen, drospirenone, in a different
      combination, has been considered more reliable in terms of risk of MI. However,
      there have been some cases of MI associated with the use of drospirenone-ethinyl
      estradiol, despite the protective effects of this oral contraceptive. In this
      report, a 33-year-old woman who had used drospirenone-ethinyl estradiol for 6
      months was admitted with MI and symptoms of cardiogenic shock. Coronary
      angiography revealed the total occlusion of 2 coronary arteries and so
      percutaneous coronary intervention was performed. To the best of our knowledge,
      this is the first case report of simultaneous total occlusion of 2 coronary
      arteries associated with the use of drospirenone-ethinyl estradiol in the English
      language medical literature.

PMID- 29339694
TI  - Aortic alpha-smooth muscle actin expressions in aortic disorders and coronary
      artery disease: An immunohistochemical study.
AB  - OBJECTIVE: The is to report immunohistochemical observations of aortic alpha
      smooth muscle actin (SMA) expressions in patients with aortic aneurysm, acute
      aortic dissection, and coronary artery disease and to discuss phenotypic
      switching of smooth muscle cells (SMCs) of these lesions. METHODS: Forty-nine
      consecutive patients scheduled for surgical treatment for acute type A aortic
      dissection (20 patients), aortic aneurysm (9 patients), and coronary artery
      disease (20 patients) were included. Surgical specimens of the aorta were
      obtained and prepared for hematoxylin and eosin and immunohistochemical
      stainings. RESULTS: A comparison of aortic structural changes between the three
      groups showed that patients with coronary artery disease had the least severe
      aorta degeneration with the most intense alpha-SMA positivity. Aortic structural
      impairment was the most severe in patients with aortic dissection, whereas alpha
      SMA positivity was more intense in patients with aortic dissection than in those
      with aortic aneurysm. CONCLUSION: Disparities in alpha-SMA expressions in the
      aortic tissues of the three groups represent the extent of SMC degenerations or a
      phenotypic switching between contractile and synthetic SMCs. The results imply
      severe SMC degenerations in patients with aortic aneurysm, which may be
      beneficial because of the production of extracellular matrix necessary for
      healing of the vascular wall, but severe disruptions in elastic fibers in
      patients with aortic dissection. Patients with coronary artery disease show
      slight SMC degeneration and phenotypic switching among the three groups. The
      possible apoptotic and genetic mechanisms of aortic structural impairments
      warrant further elaborations.

PMID- 29339695
TI  - Smooth muscle phenotype in aortic diseases: Are there other histopathological
      markers besides contractile myofibrils?

PMID- 29339696
TI  - Chronic ethanol increases calcium/calmodulin-dependent protein kinaseIIdelta gene
      expression and decreases monoamine oxidase amount in rat heart muscles: Rescue
      effect of Zingiber officinale (ginger) extract.
AB  - OBJECTIVE: Association between chronic alcohol intake and cardiac abnormality is
      well known; however, the precise underlying molecular mediators involved in
      ethanol-induced heart abnormalities remain elusive. This study investigated the
      effect of chronic ethanol exposure on calcium/calmodulin-dependent protein kinase
      IIdelta (CaMKIIdelta) gene expression and monoamine oxidase (MAO) levels and
      histological changes in rat heart. It was also planned to find out whether
      Zingiber officinale (ginger) extract mitigated the abnormalities induced by
      ethanol in rat heart. METHODS: Male wistar rats were divided into three groups of
      eight animals each: control, ethanol, and ginger extract treated-ethanol (GETE)
      groups. RESULTS: After 6 weeks of treatment, the results revealed a significant
      increase in CaMKIIdeltatotal and isoforms delta2 and delta3 of CaMKIIdelta gene
      expression as well as a significant decrease in the MAO levels in the ethanol
      group compared to that in the control group. Moreover, compared to the control
      group, the ethanol group showed histological changes, such as fibrosis, heart
      muscle cells proliferation, myocyte hypertrophy, vacuolization, and focal
      lymphocytic infiltration. Consumption of ginger extract along with ethanol
      ameliorated CaMKIIdeltatotal. In addition, compared to the ethanol group,
      isoforms gene expression changed and increased the reduced MAO levels and
      mitigated heart structural changes. CONCLUSION: These findings indicate that
      ethanol-induced heart abnormalities may, in part, be associated with Ca2+
      homeostasis changes mediated by overexpression of CaMKIIdelta gene and the
      decrease of MAO levels and that these effects can be alleviated by using ginger
      extract as an antioxidant and anti-inflammatory agent.

PMID- 29339697
TI  - The value of real-time myocardial contrast echocardiography for detecting
      coronary microcirculation function in coronary artery disease patients.
AB  - OBJECTIVE: The aim of this study was to evaluate the value of real-time
      myocardial contrast echocardiography (RT-MCE) for detecting coronary
      microcirculation (CM) function in coronary artery disease (CAD) patients.
      METHODS: Sixty-five consecutive patients were divided into CAD (n=52) and no-CAD
      (n=13) groups using coronary angiography (CAG). All patients underwent RT-MCE at
      rest and CAG within 1 week after RT-MCE. The ventricular segments in CAD patients
      were divided semi-quantitatively into ischemic and non-ischemic myocardial groups
      based on RT-MCE images. Myocardial blood volume (A), myocardial blood flow
      velocity (beta), and mean myocardial blood flow (Axbeta) were obtained. The
      Gensini scores were calculated for CAD patients. The receiver operating
      characteristic (ROC) curve areas of A, beta, and Axbeta were calculated to assess
      CM function in CAD patients. RESULTS: A total of 798 and 204 segments were
      investigated in the CAD and non-CAD groups, respectively. In CAD patients, 332
      ischemic and 466 non-ischemic segments were identified. The values of A, beta,
      and Axbeta were significantly different among non-CAD, CAD, ischemic, and
      nonischemic groups. ROC curve areas of A, beta, and Axbeta were 0.85, 0.79, and
      0.83, respectively, and significant differences were observed in these values
      among three Gensini score groups of the CAD patients. CONCLUSION: Varying degrees
      of CM function deterioration was observed in CAD patients both in ischemic and
      non-ischemic areas, with the deterioration being more sever in the former.

PMID- 29339698
TI  - Association of Interleukin-1 Gene cluster polymorphisms with coronary slow flow
      phenomenon.
AB  - OBJECTIVE: Coronary slow flow phenomenon (CSFP) is characterized by the decreased
      rate of contrast progression in epicardial coronary arteries in the absence of
      significant coronary stenosis. Mounting evidence has showed a significant
      association between inflammation and CSFP severity. This study aimed to evaluate
      possible associations between interleukin-1 receptor antagonist (IL-1ra) gene
      variable number tandem repeat (VNTR), IL-1beta -511 single nucleotide (SNP), and
      IL-1beta+3954 SNP mutations with CSFP. METHODS: Forty-eight patients with CSFP
      and 62 controls with angiographically normal coronary arteries were prospectively
      enrolled in the study. Genotypes were assessed using the polymerase chain
      reaction (PCR)-based restriction fragment length polymorphism (PCR-RFLP)
      technique. RESULTS: Homozygote genotype for allele 2 of+3954 C>T 2/2 genotype was
      significantly more frequent in patients with CSFP than in the control group,
      whereas 1/2 genotype was more frequent in the control group (35.4% versus 14.5%
      for 2/2 genotype and 25% versus 35.5% for 1/2 genotype in CSFP and control
      groups, respectively, X2=6.6; p=0.04). The allelic frequency of allele 2 of this
      polymorphism was significantly higher in the CSFP group than in the control group
      (47.9% versus 28.6% in the control group, X2=5.6; p=0.02). However, there was no
      significant difference with regard to genotype or allelic frequencies of IL-1ra
      VNTR or IL-1beta -511 SNP polymorphisms between patients with CSFP and controls.
      CONCLUSION: IL-1beta+3954 SNP mutations are significantly more common in patients
      with CSFP. It may suggest that the tendency for inflammation may contribute to
      the presence of this phenomenon.

PMID- 29339699
TI  - Impact of gender and age on the association of the BUD13-ZNF259 rs964184
      polymorphism with coronary heart disease.
AB  - OBJECTIVE: Coronary heart disease (CHD) is the most common cause of death
      worldwide. This study aimed to validate the association of the rs964184
      polymorphism with the CHD risk and included 874 CHD patients and 776 controls.
      METHODS: rs964184 polymorphism genotyping was performed using Tm-shift polymerase
      chain reaction. RESULTS: A strong association of the rs964184 polymorphism with
      CHD was found (genotype: X2=14.365, p=0.001; allele: X2=14.191, p=1.67x10-4;
      power=0.965). Gender analysis revealed a significant association only in males
      (genotype: X2=12.387, p=0.002; allele: X2=12.404, p=4.32x10-4; OR=1.467, 95%
      CI=1.185-1.817, power=0.945). Age and gender analyses revealed significant
      associations of the rs964184 polymorphism with CHD in males between the ages of
      55 and 65 years (genotype: X2=10.070, p=0.007; allele: X2=10.077, p=0.002;
      OR=1.706, 95% CI=1.224-2.377, power=0.996) and in females older than 65 years
      (genotype: X2=9.462, p=0.009; allele: X2=9.560, p=0.002; OR=2.112, 95% CI=1.308
      3.412, power=0.994). Further subgroup analysis suggested that rs964184 genotypes
      were significantly associated with TG levels in the patients (r=0.191, adjusted
      p=1.05x10-5) and controls (r=0.101, adjusted p=0.026). CONCLUSION: Our results
      indicate that both gender and age have great impacts on the association of the
      rs964184 polymorphism with CHD among Chinese.

PMID- 29339700
TI  - Assessment of the relationship between reperfusion success and T-peak to T-end
      interval in patients with ST elevation myocardial infarction treated with
      percutaneous coronary intervention.
AB  - OBJECTIVE: T-peak-T-end (TPE) interval, which represents the dispersion of
      repolarization, is defined as the interval between the peak and end of the T
      wave, and is associated with increased malignant ventricular arrhythmia and
      sudden cardiac death (SCD) in patients with ST elevation myocardial infarction
      (STEMI). Although prolonged TPE interval is associated with poor short- and long
      term outcomes, even in patients with STEMI treated with successful primary
      percutaneous coronary intervention (pPCI), clinical, angiographic, and laboratory
      parameters that affect TPE remain to be elucidated. The aim of our study was to
      evaluate the potential relationship between prolonged TPE interval and
      reperfusion success using ST segment resolution (STR) in patients with STEMI
      undergoing pPCI. METHODS: In the current study, 218 consecutive patients with
      STEMI who underwent pPCI were enrolled; after exclusion, 164 patients were
      included in the study population. RESULTS: Patients were divided into two groups
      according to the presence of complete (STR%>=70) or incomplete (STR%<70) STR.
      Preprocedural corrected TPE (cTPEPRE;116+/-21 ms vs. 108+/-21 ms; p=0.027),
      postprocedural TPE (TPEPOST; 107+/-16 ms vs. 92+/-21 ms; p<0.001), and
      postprocedural cTPE (cTPEPOST; 119+/-19 ms vs. 102+/-17 ms; p<0.001) intervals
      were significantly longer in patients with incomplete STR than in patients with
      complete STR, whereas there was no statistically significant difference between
      the two groups in terms of pre- and postprocedural and corrected QT intervals.
      cTPEPRE and cTPEPOST were found to be independent predictors for incomplete STR.
      CONCLUSION: To our knowledge, this is the first study that evaluated the
      relationship between TPE interval and no-reflow defined by STR in patients with
      STEMI who were treated with pPCI.

PMID- 29339701
TI  - Subclinical reduction in left ventricular function using triplane and 2D speckle
      tracking echocardiography after anthracycline exposure in children.
AB  - OBJECTIVE: Speckle tracking echocardiography (STE) enables global and regional
      evaluation of the left ventricle (LV); therefore, it is the most useful method
      for detecting subclinical dysfunction in patients exposed to cardiotoxic agents.
      A novel technique triplane (3P) echocardiography also allows single beat
      assessment of LV global longitudinal strain values. We firstly aimed to
      demonstrate both two-dimensional (2D)- and 3PSTE-derived LV global longitudinal
      strain measurements in children after anthracycline exposure. METHODS: This study
      included 23 cross-sectionally enrolled asymptomatic pediatric cancer patients who
      received anthracycline chemotherapy and 17 healthy controls matched by age,
      gender, and body surface area. All subjects underwent detailed 2D, Doppler, 2D
      STE, and 3P-STE for assessment of LV function. The patients had received a median
      cumulative dose of 150 mg/m2. RESULTS: 1. From "Pulsed" Doppler-based
      measurements, only pulmonary vein flow ratio showed a significant difference
      between the groups. 2. When measurements were taken from the interventricular
      septum, the patients' ejection time values decreased significantly and their
      myocardial performance index values increased significantly; when the
      measurements were taken from the LV free wall, the peak systolic velocities
      showed a statistically significant difference. 3. Both 2D- and 3P-STE-derived
      longitudinal myocardial deformation values of LV were lower in the patient group.
      4. 2D-STE-derived LV circumferential strain values were decreased in the patient
      group, whereas radial strain values were not significantly different compared
      with matched controls. CONCLUSION: Using Doppler and 2D- and 3P-STE methods, this
      study confirmed the subclinical LV dysfunction in patients after anthracycline
      exposure.

PMID- 29339702
TI  - Efficacy and safety of oral anticoagulation in elderly patients with atrial
      fibrillation.
AB  - Elderly patients with atrial fibrillation are at a higher risk of both ischemic
      and bleeding events compared with younger patients; therefore, balancing risks
      and benefits of antithrombotic strategies in this population is crucial. Recent
      studies have shown that because the risk of stroke increases with age more than
      the risk of bleeding, the absolute benefit of oral anticoagulation is the highest
      in elderly patients in whom it outweighs the risk of bleeding. Direct oral
      anticoagulants (DOACs) have been developed as a treatment for the prevention of
      cardioembolic stroke to overcome some limitations of warfarin, such as the need
      for frequent monitoring, labile INR values requiring frequent dose adjustment,
      dietary and drugs interactions, and increased risk of intracranial bleeding.
      Despite the better safety profiles of DOACs compared with warfarin, elderly
      patients often remain undertreated because of the fear of bleeding complications.
      This review summarizes current evidence regarding the risks of thromboembolisms
      and bleeding in different antithrombotic strategies in elderly patients (aged
      >=75 years) with atrial fibrillation, including data from the warfarin-controlled
      phase 3 DOACs trials.

PMID- 29339703
TI  - A case of asymptomatic large aortopulmonary window in an adult: Role of cardiac
      CT, CMRI, and 3D printing technology.

PMID- 29339704
TI  - Valve-sparing aortic root replacement in Loeys-Dietz syndrome and a novel
      mutation in TGFBR2.

PMID- 29339705
TI  - A sad story of a man with two ventricles.

PMID- 29339706
TI  - Tolvaptan should be used very carefully in very elderly patients.

PMID- 29339707
TI  - Author's Reply.

PMID- 29339708
TI  - Simultaneous subacute thrombosis in two new-generation drug-eluting stents in
      different vessels.

PMID- 29339709
TI  - Short-term evolution of cardiac structure and function in patients on maintenance
      hemodialysis for end-stage renal disease: A quasi-experimental, non-randomized,
      evaluation echocardiography study in Cameroon, sub-Saharan Africa.

PMID- 29339710
TI  - A case of acute intrastent thrombosis accompanied by arterial thrombosis in the
      lower extremities after percutaneous coronary intervention.

PMID- 29339711
TI  - Unusual combination of mitral valve prolapse, bicuspid aortic valve, and
      ventricular septal defect restricted by the tricuspid septal leaflet.

PMID- 29339712
TI  - A New Year, A New Time.

PMID- 29339713
TI  - Neuroprotective effect of selective antegrade cerebral perfusion during prolonged
      deep hypothermic circulatory arrest: Cerebral metabolism evidence in a pig model.
AB  - OBJECTIVE: The aim of this study was to elucidate the mechanism of cerebral
      injury and to evaluate selective antegrade cerebral perfusion (SACP) as a
      superior neuroprotective strategy for prolonged deep hypothermic circulatory
      arrest (DHCA). METHODS: Twelve pigs (6-8-week old) were randomly assigned to DHCA
      alone (n=6) and DHCA with SACP (n=6) at 18 degrees C for 80 min groups. Serum
      S100 was determined using an immunoassay analyzer. The concentrations of cerebral
      dialysate glucose, lactate, pyruvate, glycerol, and glutamate were measured using
      a microdialysis analyzer. RESULTS: Compared with a peak at T4 (after 60 min of
      rewarming) in the DHCA group, the serum S100 in the SACP group was significantly
      lower throughout the study. The DHCA group was susceptible to significant
      increases in the levels of lactate, glycerol, and glutamate and the ratio of
      lactate/pyruvate as well as decreases in the level of glucose. These
      microdialysis variables showed only minor changes in the SACP group. There was a
      positive correlation between cerebral lactate and intracranial pressure during
      reperfusion in the DHCA group. However, the apoptosis index and C-FOS protein
      levels were lower in the SACP group. CONCLUSION: Metabolic dysfunction is
      involved in the mechanism of cerebral injury. SACP is a superior neuroprotective
      strategy for both mild and prolonged DHCA.

PMID- 29339714
TI  - Stent thrombosis in patients with drug--eluting stents and bioresorbable vascular
      scaffolds: the feared complication.
AB  - The percutaneous coronary intervention (PCI) has undergone rapid evolution over
      the last 40 years and has become one of the most widely performed medical
      procedures. The introduction of intracoronary stents has improved the safety and
      efficacy of PCI. However, with the advent of stenting, a new potentially fatal
      enemy has emerged: stent thrombosis. Ever since, adjunct pharmacological therapy,
      stent technique, and technology have been adjusted to reduce the risk of stent
      thrombosis. The aim of the present article is to provide an overview of the past,
      present, and future aspects of PCI in relation to stent thrombosis.

PMID- 29339715
TI  - Caveolin-1 Inhibits Proliferation, Migration, and Invasion of Human Colorectal
      Cancer Cells by Suppressing Phosphorylation of Epidermal Growth Factor Receptor.
AB  - BACKGROUND Although downregulation of caveolin-1 (Cav-1), which is a key
      constituent of membrane caveolae and a regulator of cellular processes, is
      associated with colorectal cancer (CRC), its involvement in the disease
      progression is largely unknown. This study aimed to explore the role of Cav-1 in
      CRC and the associated mechanisms. MATERIAL AND METHODS Fresh tissues from
      patients with CRC and human CRC SW480 cells were used to evaluate Cav-1 and Ki-67
      expression using immunohistochemistry and Western blotting. The MTS and Transwell
      assays were performed to determine the effects of Cav-1 overexpression via
      pcDNA3.1/Cav-1 plasmid on cell proliferation and metastasis. The effect of Cav-1
      on the epidermal growth factor receptor (EGFR) activation was evaluated by
      Western blotting. The correlation of Cav-1 expression with clinicopathological
      factors was statistically analyzed. RESULTS Overexpression of Cav-1 significantly
      reduced proliferation, migration, and invasion of SW480 cancer cells in vitro.
      The EGF-induced phosphorylation of EGFR and activations of the RAF-MEK-ERK and
      PI3K-AKT pathways were adversely regulated by Cav-1 overexpression in vitro. In
      76 cases of CRC patients with EGFR expression, a negative correlation was
      observed between the level of Cav-1 and tumor-node-metastasis stage, lymph node
      metastasis, and distant metastasis (All p<0.05). Finally, the expression level of
      Cav-1 was negatively correlated with that of Ki-67. CONCLUSIONS This report is
      the first to show that overexpression of Cav-1significantly inhibits the
      proliferation, migration, and invasion potential of SW480 cells, possibly through
      reducing EGF-induced EGFR activation. High Cav-1 expression level may be a
      predictor of positive outcomes in patients with colorectal cancer.

PMID- 29339716
TI  - To Explore the Mechanism of the GRM4 Gene in Osteosarcoma by RNA Sequencing and
      Bioinformatics Approach.
AB  - BACKGROUND Glutamate metabotropic receptor 4 (GRM4) has been correlated with the
      pathogenesis of osteosarcoma. The objective of this study was to explore the
      underlying molecular mechanism of GRM4 in osteosarcoma. MATERIAL AND METHODS The
      expression levels of GRM4 in four human osteosarcoma cell lines and hFOB1.19
      cells were examined by real-time quantitative PCR (RT-qPCR). The U2OS cells of
      the highest GRM4 expression were transfected with lentivirus-mediated small
      interfering RNA (siRNA). The differentially expressed genes (DEGs) after GRM4
      gene silencing were screened through RNA sequencing, and analyzed by
      bioinformatics. Additionally, the transcription factors (TFs) targeting GRM4 were
      predicted and the downstream protein-protein interaction (PPI) network was
      constructed using the bioinformatics approach. RESULTS A total of 51 significant
      DEGs were obtained, including 14 upregulated and 37 downregulated DEGs. The Kyoto
      Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the DEGs
      indicated that four significant enrichment pathways were obtained. A total of six
      TFs that could be involved in the transcriptional regulation of GRM4 were
      detected. The results showed that 182 genes in the PPI network were significantly
      enriched in 14 pathways. The chemokines and chemokine receptors were found to be
      significantly enriched in three pathways. CONCLUSIONS The DEGs in the four
      significant enrichment pathways might participate in the development and
      progression of osteosarcoma through GRM4. The results revealed that EGR1 and CTCF
      are probably involved in the transcriptional regulation of GRM4, which
      participates in the progress of osteosarcoma by interacting with chemokines and
      their receptors.

PMID- 29339717
TI  - Complex Reconstruction with Flaps After Abdominoperineal Resection and Groin
      Dissection for Anal Squamous Cell Carcinoma: A Difficult Case Involving Many
      Specialities.
AB  - BACKGROUND Anal squamous cell carcinoma accounts for about 2-4% of all lower
      gastrointestinal malignancies, with a distant disease reported in less than 5%.
      Although surgical treatment is rarely necessary, this often involve large
      dissections and difficult reconstructive procedures. CASE REPORT We present a
      complex but successful case of double-flap reconstruction after abdominoperineal
      resection and groin dissection for anal squamous cell carcinoma (cT3N3M0) with
      metastatic right inguinal lymph nodes and ipsilateral threatening of femoral
      vessels. A multi-specialty team was involved in the operation. A vascular and
      plastic surgeon performed the inguinal dissection with en bloc excision of the
      saphenous magna and a cuff of the femoral vein, while colorectal surgeons carried
      out the abdominoperineal excision. The 2 large tissue gaps at the groin and
      perineum were covered with an oblique rectus abdominis myocutaneous flap and a
      gluteal lotus flap, respectively. A partially absorbable mesh was placed at the
      level of the anterior sheath in order to reinforce the abdominal wall, whereas an
      absorbable mesh was used as a bridge for the dissected pelvic floor muscles. The
      post-operative period was uneventful and the follow-up at 5 months showed good
      results. CONCLUSIONS An early diagnosis along with new techniques of
      radiochemotherapy allow patients to preserve their sphincter function. However, a
      persistent or recurrent disease needs major operations, which often involve a
      complex reconstruction. Good team-work and experience in specialized fields give
      the opportunity to make the best choices to perform critical steps during the
      management of complex cases.

PMID- 29339718
TI  - Injury-activated glial cells promote wound healing of the adult skin in mice.
AB  - Cutaneous wound healing is a complex process that aims to re-establish the
      original structure of the skin and its functions. Among other disorders,
      peripheral neuropathies are known to severely impair wound healing capabilities
      of the skin, revealing the importance of skin innervation for proper repair.
      Here, we report that peripheral glia are crucially involved in this process.
      Using a mouse model of wound healing, combined with in vivo fate mapping, we show
      that injury activates peripheral glia by promoting de-differentiation, cell-cycle
      re-entry and dissemination of the cells into the wound bed. Moreover, injury
      activated glia upregulate the expression of many secreted factors previously
      associated with wound healing and promote myofibroblast differentiation by
      paracrine modulation of TGF-beta signalling. Accordingly, depletion of these
      cells impairs epithelial proliferation and wound closure through contraction,
      while their expansion promotes myofibroblast formation. Thus, injury-activated
      glia and/or their secretome might have therapeutic potential in human wound
      healing disorders.

PMID- 29339719
TI  - miR-181a-5p suppresses invasion and migration of HTR-8/SVneo cells by directly
      targeting IGF2BP2.
AB  - Pre-eclampsia is a pregnancy-related disease that may cause maternal, neonatal
      and fetal morbidity and mortality and exists in 3-5% of pregnancies worldwide.
      The discovery of dysregulated microRNAs and their roles in placental development
      has provided a new avenue for elucidating the mechanism involved in this
      pregnancy-specific disorder. Here, the roles of human miR-181a-5p, a microRNA
      that is increased in both the plasma and placenta of severe pre-eclamptic
      patients, in invasion and migration of trophoblasts were investigated. Ectopic
      expression of miR-181a-5p impaired the invasion and migration of HTR-8/SVneo
      cells, whereas miR-181a-5p inhibition had the opposite effects. IGF2BP2, which
      harbors a highly conserved miR-181a-5p-binding site within its 3'-UTR, was
      identified to be directly inhibited by miR-181a-5p. Moreover, siRNAs targeting
      IGF2BP2 imitated the effects of overexpressed miR-181a-5p on HTR-8/SVneo cell
      invasion and migration, whereas restoring IGF2BP2 expression by overexpressing a
      plasmid encoding IGF2BP2 partially reversed the studied inhibitory functions of
      miR-181a-5p. Thus, we demonstrated here that miR-181a-5p suppresses the invasion
      and migration of cytotrophoblasts, and its inhibitory effects were at least
      partially mediated by the suppression of IGF2BP2 expression, thus shedding new
      light on the roles of miR-181a-5p in the pathogenesis of severe pre-eclampsia.

PMID- 29339720
TI  - Plumbagin inhibits the proliferation and survival of esophageal cancer cells by
      blocking STAT3-PLK1-AKT signaling.
AB  - Esophageal squamous cell carcinoma (ESCC) is one of the deadliest cancers, and it
      requires novel treatment approaches and effective drugs. In the present study, we
      found that treatment with plumbagin, a natural compound, reduced proliferation
      and survival of the KYSE150 and KYSE450 ESCC cell lines in a dose-dependent
      manner in vitro. The drug also effectively inhibited the viability of primary
      ESCC cells from fresh biopsy specimens. Furthermore, plumbagin-induced mitotic
      arrest and massive apoptosis in ESCC cells. Notably, the drug significantly
      suppressed the colony formation capacity of ESCC cells in vitro and the growth of
      KYSE150 xenograft tumors in vivo. At the molecular level, we found that exposure
      to plumbagin decreased both polo-like kinase 1 (PLK1) and phosphorylated protein
      kinase B (p-AKT) expression in both ESCC cell lines. Enforced PLK1 expression in
      ESCC cells not only markedly rescued cells from plumbagin-induced apoptosis and
      proliferation inhibition but also restored the impaired AKT activity.
      Furthermore, signal transducer and activator of transcription 3 (STAT3), a
      transcription factor of PLK1, was also inactivated in plumbagin-treated ESCC
      cells; however, the overexpression of a constitutively activated STAT3 mutant,
      STAT3C, reinstated the plumbagin-elicited blockade of PLK1-AKT signaling in ESCC
      cells. Taken together, these findings indicate that plumbagin inhibits
      proliferation and potentiates apoptosis in human ESCC cells in vitro and in vivo.
      Plumbagin may exert these antitumor effects by abrogating STAT3-PLK1-AKT
      signaling, which suggests that plumbagin may be a novel, promising anticancer
      agent for the treatment of ESCC.

PMID- 29339721
TI  - Single-molecule FRET reveals multiscale chromatin dynamics modulated by HP1alpha.
AB  - The dynamic architecture of chromatin fibers, a key determinant of genome
      regulation, is poorly understood. Here, we employ multimodal single-molecule
      Forster resonance energy transfer studies to reveal structural states and their
      interconversion kinetics in chromatin fibers. We show that nucleosomes engage in
      short-lived (micro- to milliseconds) stacking interactions with one of their
      neighbors. This results in discrete tetranucleosome units with distinct
      interaction registers that interconvert within hundreds of milliseconds.
      Additionally, we find that dynamic chromatin architecture is modulated by the
      multivalent architectural protein heterochromatin protein 1alpha (HP1alpha),
      which engages methylated histone tails and thereby transiently stabilizes stacked
      nucleosomes. This compacted state nevertheless remains dynamic, exhibiting
      fluctuations on the timescale of HP1alpha residence times. Overall, this study
      reveals that exposure of internal DNA sites and nucleosome surfaces in chromatin
      fibers is governed by an intrinsic dynamic hierarchy from micro- to milliseconds,
      allowing the gene regulation machinery to access compact chromatin.

PMID- 29339722
TI  - The deep-subsurface sulfate reducer Desulfotomaculum kuznetsovii employs two
      methanol-degrading pathways.
AB  - Methanol is generally metabolized through a pathway initiated by a cobalamine
      containing methanol methyltransferase by anaerobic methylotrophs (such as
      methanogens and acetogens), or through oxidation to formaldehyde using a methanol
      dehydrogenase by aerobes. Methanol is an important substrate in deep-subsurface
      environments, where thermophilic sulfate-reducing bacteria of the genus
      Desulfotomaculum have key roles. Here, we study the methanol metabolism of
      Desulfotomaculum kuznetsovii strain 17T, isolated from a 3000-m deep geothermal
      water reservoir. We use proteomics to analyze cells grown with methanol and
      sulfate in the presence and absence of cobalt and vitamin B12. The results
      indicate the presence of two methanol-degrading pathways in D. kuznetsovii, a
      cobalt-dependent methanol methyltransferase and a cobalt-independent methanol
      dehydrogenase, which is further confirmed by stable isotope fractionation. This
      is the first report of a microorganism utilizing two distinct methanol conversion
      pathways. We hypothesize that this gives D. kuznetsovii a competitive advantage
      in its natural environment.

PMID- 29339723
TI  - Fasoracetam in adolescents with ADHD and glutamatergic gene network variants
      disrupting mGluR neurotransmitter signaling.
AB  - The glutamatergic neurotransmitter system may play an important role in attention
      deficit hyperactivity disorder (ADHD). This 5-week, open-label, single-blind,
      placebo-controlled study reports the safety, pharmacokinetics and responsiveness
      of the metabotropic glutamate receptor (mGluR) activator fasoracetam (NFC-1), in
      30 adolescents, age 12-17 years with ADHD, harboring mutations in mGluR network
      genes. Mutation status was double-blinded. A single-dose pharmacokinetic
      profiling from 50-800 mg was followed by a single-blind placebo at week 1 and
      subsequent symptom-driven dose advancement up to 400 mg BID for 4 weeks. NFC-1
      treatment resulted in significant improvement. Mean Clinical Global Impressions
      Improvement (CGI-I) and Severity (CGI-S) scores were, respectively, 3.79 at
      baseline vs. 2.33 at week 5 (P < 0.001) and 4.83 at baseline vs. 3.86 at week 5
      (P < 0.001). Parental Vanderbilt scores showed significant improvement for
      subjects with mGluR Tier 1 variants (P < 0.035). There were no differences in the
      incidence of adverse events between placebo week and weeks on active drug. The
      trial is registered at https://clinicaltrials.gov/ct2/show/study/NCT02286817 .

PMID- 29339724
TI  - Granulocyte-colony stimulating factor controls neural and behavioral plasticity
      in response to cocaine.
AB  - Cocaine addiction is characterized by dysfunction in reward-related brain
      circuits, leading to maladaptive motivation to seek and take the drug. There are
      currently no clinically available pharmacotherapies to treat cocaine addiction.
      Through a broad screen of innate immune mediators, we identify granulocyte-colony
      stimulating factor (G-CSF) as a potent mediator of cocaine-induced adaptations.
      Here we report that G-CSF potentiates cocaine-induced increases in neural
      activity in the nucleus accumbens (NAc) and prefrontal cortex. In addition, G-CSF
      injections potentiate cocaine place preference and enhance motivation to self
      administer cocaine, while not affecting responses to natural rewards. Infusion of
      G-CSF neutralizing antibody into NAc blocks the ability of G-CSF to modulate
      cocaine's behavioral effects, providing a direct link between central G-CSF
      action in NAc and cocaine reward. These results demonstrate that manipulating G
      CSF is sufficient to alter the motivation for cocaine, but not natural rewards,
      providing a pharmacotherapeutic avenue to manipulate addictive behaviors without
      abuse potential.

PMID- 29339725
TI  - TGR5 signalling promotes mitochondrial fission and beige remodelling of white
      adipose tissue.
AB  - Remodelling of energy storing white fat into energy expending beige fat could be
      a promising strategy to reduce adiposity. Here, we show that the bile acid
      responsive membrane receptor TGR5 mediates beiging of the subcutaneous white
      adipose tissue (scWAT) under multiple environmental cues including cold exposure
      and prolonged high-fat diet feeding. Moreover, administration of TGR5-selective
      bile acid mimetics to thermoneutral housed mice leads to the appearance of beige
      adipocyte markers and increases mitochondrial content in the scWAT of Tgr5 +/+
      mice but not in their Tgr5 -/- littermates. This phenotype is recapitulated in
      vitro in differentiated adipocytes, in which TGR5 activation increases free fatty
      acid availability through lipolysis, hence fuelling beta-oxidation and
      thermogenic activity. TGR5 signalling also induces mitochondrial fission through
      the ERK/DRP1 pathway, further improving mitochondrial respiration. Taken
      together, these data identify TGR5 as a druggable target to promote beiging with
      potential applications in the management of metabolic disorders.

PMID- 29339726
TI  - Publisher Correction: Identification and characterization of two functional
      variants in the human longevity gene FOXO3.
AB  - The original version of this Article contained an error in the spelling of the
      author Robert Hasler, which was incorrectly given as Robert Haesler. This has now
      been corrected in both the PDF and HTML versions of the Article.

PMID- 29339727
TI  - Analysis of criteria for treatment initiation in patients with progressive
      chronic lymphocytic leukemia.

PMID- 29339728
TI  - How BMP-2 induces EMT and breast cancer stemness through Rb and CD44?

PMID- 29339729
TI  - Ecotropic viral integration site 1 promotes metastasis independent of epithelial
      mesenchymal transition in colon cancer cells.
AB  - The most indecipherable component of solid cancer is the development of
      metastasis which accounts for more than 90% of cancer-related mortalities. A
      developmental program termed epithelial-mesenchymal transition (EMT) has also
      been shown to play a critical role in promoting metastasis in epithelium-derived
      solid tumors. By analyzing publicly available microarray datasets, we observed
      that ecotropic viral integration site 1 (EVI1) correlates negatively with SLUG, a
      master regulator of EMT. This correlation was found to be relevant as we
      demonstrated that EVI1 binds to SLUG promoter element directly through the distal
      set of zinc fingers and downregulates its expression. Many studies have shown
      that the primary role of SLUG during EMT and EMT-like processes is the regulation
      of cell motility in most of the cancer cells. Knockdown of EVI1 in metastatic
      colon cancer cell and subsequent passage through matrigel not only increased the
      invading capacity but also induced an EMT-like morphological feature of the
      cells, such as spindle-shaped appearance and led to a significant reduction in
      the expression of the epithelial marker, E-CADHERIN and increase in the
      expression of the mesenchymal marker, N-CADHERIN. The cells, when injected into
      immunocompromised mice, failed to show any metastatic foci in distant organs
      however the ones with EVI1, metastasized in the intraperitoneal layer and also
      showed multiple micro metastatic foci in the lungs and spleen. These findings
      suggest that in colon cancer EVI1 is dispensable for epithelial-mesenchymal
      transition, however, is required for metastasis.

PMID- 29339730
TI  - Mutational heterogeneity of angioimmunoblastic T-cell lymphoma indicates distinct
      lymphomagenic pathways.

PMID- 29339731
TI  - Electron affinity of liquid water.
AB  - Understanding redox and photochemical reactions in aqueous environments requires
      a precise knowledge of the ionization potential and electron affinity of liquid
      water. The former has been measured, but not the latter. We predict the electron
      affinity of liquid water and of its surface from first principles, coupling path
      integral molecular dynamics with ab initio potentials, and many-body perturbation
      theory. Our results for the surface (0.8 eV) agree well with recent pump-probe
      spectroscopy measurements on amorphous ice. Those for the bulk (0.1-0.3 eV)
      differ from several estimates adopted in the literature, which we critically
      revisit. We show that the ionization potential of the bulk and surface are almost
      identical; instead their electron affinities differ substantially, with the
      conduction band edge of the surface much deeper in energy than that of the bulk.
      We also discuss the significant impact of nuclear quantum effects on the
      fundamental gap and band edges of the liquid.

PMID- 29339732
TI  - Glyburide and retinoic acid synergize to promote wound healing by anti
      inflammation and RIP140 degradation.
AB  - Chronic inflammation underlies the development of metabolic diseases and
      individuals with metabolic disease often also suffer from delayed wound healing
      due to prolonged inflammation. Resolving inflammation provides a therapeutic
      strategy in treating metabolic diseases. We previously showed that during an anti
      inflammatory response when macrophages were alternatively (M2) polarized,
      retinoic acid (RA) dramatically activated arginase 1 gene (Arg1), a gene crucial
      for wound healing. Here we report that a widely used sulfonylurea drug for type 2
      diabetes mellitus (T2DM), glyburide, enhances the anti-inflammatory response and
      synergizes with RA to promote wound healing. Our data also delineate the
      mechanism underlying glyburide's anti-inflammatory effect, which is to stimulate
      the degradation of a pro-inflammatory regulator, Receptor Interacting Protein 140
      (RIP140), by activating Ca2+/calmodulin-dependent protein kinase II (CamKII) that
      triggers specific ubiquitination of RIP140 for degradation. By stimulating RIP140
      degradation, glyburide enhances M2 polarization and anti-inflammation. Using a
      high-fat diet induced obesity mouse model to monitor wound healing effects, we
      provide a proof-of-concept for a therapeutic strategy that combining glyburide
      and RA can significantly improve wound healing. Mechanistically, this study
      uncovers a new mechanism of action of glyburide and a new pathway modulating
      RIP140 protein degradation that is mediated by CamKII signaling.

PMID- 29339733
TI  - Role of Macromolecular Crowding on the Intracellular Diffusion of DNA Binding
      Proteins.
AB  - Recent experiments suggest that cellular crowding facilitates the target search
      dynamics of proteins on DNA, the mechanism of which is not yet known. By using
      large scale computer simulations, we show that two competing factors, namely the
      width of the depletion layer that separates the crowder cloud from the DNA
      molecule and the degree of protein-crowder crosstalk, act in harmony to affect
      the target search dynamics of proteins. The impacts vary from nonspecific to
      specific target search regime. During a nonspecific search, dynamics of a protein
      is only minimally affected, whereas, a significantly different behaviour is
      observed when the protein starts forming a specific protein-DNA complex. We also
      find that the severity of impacts largely depends upon physiological crowder
      concentration and deviation from it leads to attenuation in the binding kinetics.
      Based on extensive kinetic study and binding energy landscape analysis, we
      further present a comprehensive molecular description of the search process that
      allows us to interpret the experimental findings.

PMID- 29339734
TI  - Au@Nb@H x K1-xNbO3 nanopeapods with near-infrared active plasmonic hot-electron
      injection for water splitting.
AB  - Full-spectrum utilization of diffusive solar energy by a photocatalyst for
      environmental remediation and fuel generation has long been pursued. In contrast
      to tremendous efforts in the UV-to-VIS light regime of the solar spectrum, the
      NIR and IR areas have been barely addressed although they represent about 50% of
      the solar flux. Here we put forward a biomimetic photocatalyst blueprint that
      emulates the growth pattern of a natural plant-a peapod-to address this issue.
      This design is exemplified via unidirectionally seeding core-shell Au@Nb
      nanoparticles in the cavity of semiconducting H x K1-xNbO3 nanoscrolls. The
      biomimicry of this nanopeapod (NPP) configuration promotes near-field plasmon
      plasmon coupling between bimetallic Au@Nb nanoantennas (the peas), endowing the
      UV-active H x K1-xNbO3 semiconductor (the pods) with strong VIS and NIR light
      harvesting abilities. Moreover, the characteristic 3D metal-semiconductor
      junction of the Au@Nb@H x K1-xNbO3 NPPs favors the transfer of plasmonic hot
      carriers to trigger dye photodegradation and water photoelectrolysis as proofs-of
      concept. Such broadband solar spectral response renders the Au@Nb@H x K1-xNbO3
      NPPs highly promising for widespread photoactive devices.

PMID- 29339735
TI  - Phenotype and Functional Features of Human Telomerase Reverse Transcriptase
      Immortalized Human Airway Smooth Muscle Cells from Asthmatic and Non-Asthmatic
      Donors.
AB  - Asthma is an obstructive respiratory disease characterised by chronic
      inflammation with airway hyperresponsiveness. In asthmatic airways, there is an
      increase in airway smooth muscle (ASM) cell bulk, which differs from non
      asthmatic ASM in characteristics. This study aimed to assess the usefulness of
      hTERT immortalisation of human ASM cells as a research tool. Specifically we
      compared proliferative capacity, inflammatory mediator release and extracellular
      matrix (ECM) production in hTERT immortalised and parent primary ASM cells from
      asthmatic and non-asthmatic donors. Our studies revealed no significant
      differences in proliferation, IL-6 and eotaxin-1 production, or CTGF synthesis
      between donor-matched parent and hTERT immortalised ASM cell lines. However,
      deposition of ECM proteins fibronectin and fibulin-1 was significantly lower in
      immortalised ASM cells compared to corresponding primary cells. Notably,
      previously reported differences in proliferation and inflammatory mediator
      release between asthmatic and non-asthmatic ASM cells were retained, but
      excessive ECM protein deposition in asthmatic ASM cells was lost in hTERT ASM
      cells. This study shows that hTERT immortalised ASM cells mirror primary ASM
      cells in proliferation and inflammatory profile characteristics. Moreover, we
      demonstrate both strengths and weaknesses of this immortalised cell model as a
      representation of primary ASM cells for future asthma pathophysiological
      research.

PMID- 29339736
TI  - Groups clapping in unison undergo size-dependent error-induced frequency
      increase.
AB  - Humans clapping together in unison is a familiar and robust example of emergent
      synchrony. We find that in experiments, such groups (from two to a few hundred)
      always increase clapping frequency, and larger groups increase more quickly.
      Based on single-person experiments and modeling, an individual tendency to rush
      is ruled out as an explanation. Instead, an asymmetric sensitivity in aural
      interactions explains the frequency increase, whereby individuals correct more
      strongly to match neighbour claps that precede their own clap, than those that
      follow it. A simple conceptual coupled oscillator model based on this interaction
      recovers the main features observed in experiments, and shows that the collective
      frequency increase is driven by the small timing errors in individuals, and the
      resulting inter-individual interactions that occur to maintain unison.

PMID- 29339737
TI  - Breakdown of Kasha's Rule in a Ubiquitous, Naturally Occurring, Wide Bandgap
      Aluminosilicate (Feldspar).
AB  - Excitation-energy-dependent emission (EDE) is well known from photoluminescence
      (PL) studies of polar solvents and carbon-based nanostructures. In polar
      solvents, this effect known as the 'red edge effect' (REE) is understood to arise
      from solute-solvent interactions, whereas, in case of carbon-based
      nanostructures, the origin is highly debated. Understanding this effect has
      important bearings on the potential applications of these materials. EDE has
      never been reported from large crystalline materials, except very recently by our
      group. Here, we make detailed investigations to understand the universality and
      the mechanism behind the EDE in a wide band gap aluminosilicate (feldspar), which
      comprises more than half of the Earth's crust, and is widely used in geophotonics
      (e.g., optical dating). We observe EDE up to 150 nm at room temperature in our
      samples, which is unprecedented in rigid macroscopic structures. Based on PL
      investigations at 295 K and 7 K, we present a novel model that is based on
      photoionisation of a deep lying defect and subsequent transport/relaxation of
      free electrons in the sub-conduction band tail states. Our model has important
      implications for potential photonic applications using feldspar, measurement of
      band tail width in wide bandgap materials, and understanding the EDE effect in
      other materials.

PMID- 29339738
TI  - DNA methyltransferase inhibition upregulates MHC-I to potentiate cytotoxic T
      lymphocyte responses in breast cancer.
AB  - Potentiating anti-tumor immunity by inducing tumor inflammation and T cell
      mediated responses are a promising area of cancer therapy. Immunomodulatory
      agents that promote these effects function via a wide variety of mechanisms,
      including upregulation of antigen presentation pathways. Here, we show that major
      histocompatibility class-I (MHC-I) genes are methylated in human breast cancers,
      suppressing their expression. Treatment of breast cancer cell lines with a next
      generation hypomethylating agent, guadecitabine, upregulates MHC-I expression in
      response to interferon-gamma. In murine tumor models of breast cancer,
      guadecitabine upregulates MHC-I in tumor cells promoting recruitment of CD8+ T
      cells to the microenvironment. Finally, we show that MHC-I genes are upregulated
      in breast cancer patients treated with hypomethylating agents. Thus, the
      immunomodulatory effects of hypomethylating agents likely involve upregulation of
      class-I antigen presentation to potentiate CD8+ T cell responses. These
      strategies may be useful to potentiate anti-tumor immunity and responses to
      checkpoint inhibition in immune-refractory breast cancers.

PMID- 29339740
TI  - Understanding turbulent free-surface vortex flows using a Taylor-Couette flow
      analogy.
AB  - Free-surface vortices have long been studied to develop an understanding of
      similar rotating flow phenomena observed in nature and technology. However, a
      complete description of its turbulent three-dimensional flow field still remains
      elusive. In contrast, the related Taylor-Couette flow system has been well
      explicated which classically exhibits successive instability phases manifested in
      so-called Taylor vortices. In this study, observations made on the turbulent free
      surface vortex revealed distinguishable, time-dependent "Taylor-like" vortices in
      the secondary flow field similar to the Taylor-Couette flow system. The
      observations were enabled by an original application of 2D ultrasonic Doppler
      velocity profiling complemented with laser induced fluorescence dye observations.
      Additional confirmation was provided by three-dimensional numerical simulations.
      Using Rayleigh's stability criterion, we analytically show that a wall bounded
      free-surface vortex can indeed become unstable due to a centrifugal driving force
      in a similar manner to the Taylor-Couette flow. Consequently, it is proposed that
      the free-surface vortex can be treated analogously to the Taylor-Couette flow
      permitting advanced conclusions to be drawn on its flow structure and the various
      states of free-surface vortex flow stability.

PMID- 29339739
TI  - Newborn screening of glucose-6-phosphate dehydrogenase deficiency in Guangxi,
      China: determination of optimal cutoff value to identify heterozygous female
      neonates.
AB  - The aim of this study is to assess the disease incidence and mutation spectrum of
      glucose-6-phosphate dehydrogenase (G6PD) deficiency in Guangxi, China, and to
      determine an optimal cutoff value to identify heterozygous female neonates. A
      total of 130, 635 neonates were screened from the year of 2013 to 2017. Neonates
      suspected for G6PD deficiency were further analyzed by quantitatively enzymatic
      assay and G6PD mutation analysis. The overall incidence of G6PD deficiency was
      7.28%. A total of 14 G6PD mutations were identified, and different mutations lead
      to varying levels of G6PD enzymatic activities. The best cut-off value of G6PD
      activity in male subjects is 2.2 U/g Hb, same as conventional setting. In female
      population, however, the cut-off value is found to be 2.8 U/g Hb (sensitivity:
      97.5%, specificity: 87.7%, AUC: 0.964) to best discriminate between normal and
      heterozygotes, and 1.6 U/g Hb (sensitivity: 82.2%, specificity: 85.9%, AUC:
      0.871) between heterozygotes and deficient subjects. In conclusion, we have
      conducted a comprehensive newborn screening of G6PD deficiency in a large cohort
      of population from Guangxi, China, and first established a reliable cut-off value
      of G6PD activity to distinguish heterozygous females from either normal or
      deficient subjects.

PMID- 29339741
TI  - Mesoscale Dzyaloshinskii-Moriya interaction: geometrical tailoring of the
      magnetochirality.
AB  - Crystals with broken inversion symmetry can host fundamentally appealing and
      technologically relevant periodical or localized chiral magnetic textures. The
      type of the texture as well as its magnetochiral properties are determined by the
      intrinsic Dzyaloshinskii-Moriya interaction (DMI), which is a material property
      and can hardly be changed. Here we put forth a method to create new artificial
      chiral nanoscale objects with tunable magnetochiral properties from standard
      magnetic materials by using geometrical manipulations. We introduce a mesoscale
      Dzyaloshinskii-Moriya interaction that combines the intrinsic spin-orbit and
      extrinsic curvature-driven DMI terms and depends both on the material and
      geometrical parameters. The vector of the mesoscale DMI determines magnetochiral
      properties of any curved magnetic system with broken inversion symmetry. The
      strength and orientation of this vector can be changed by properly choosing the
      geometry. For a specific example of nanosized magnetic helix, the same material
      system with different geometrical parameters can acquire one of three zero
      temperature magnetic phases, namely, phase with a quasitangential magnetization
      state, phase with a periodical state and one intermediate phase with a periodical
      domain wall state. Our approach paves the way towards the realization of a new
      class of nanoscale spintronic and spinorbitronic devices with the geometrically
      tunable magnetochirality.

PMID- 29339742
TI  - SLAF-based high-density genetic map construction and QTL mapping for major
      economic traits in sea urchin Strongylocentrotus intermedius.
AB  - Sea urchin (Strongylocentrotus intermedius) has long been a model species for
      developmental and evolutionary research, but only a few studies have focused on
      gene mapping. Here, we reported a high-density genetic map containing 4,387
      polymorphism specific-length amplified fragment (SLAF) markers spanning 21
      linkage groups (LG) for sea urchin. Based on this genetic map and phenotyping
      data for eight economic traits, 33 potentially significant QTLs were detected on
      ten different LGs with explanations ranging from 9.90% to 46.30%, partly
      including 10 QTLs for test diameter, six QTLs for body weight and eight QTLs for
      Aristotle's lantern weight. Moreover, we found a QTL enrichment LG, LG15,
      gathering QTLs for test diameter, body weight, gonad weight, light orange-yellow
      color difference (>=E1) and light yellow color difference (>=E2). Among all QTLs,
      we genotyped four QTLs for test diameter, Aristotle's lantern weight and body
      weight using High Resolution Melting (HRM) technology. Finally, we used the
      verified SNP marker (detected using SLAF sequencing) to explore their marker
      assisted selection (MAS) breeding application potential and found that SNP-29
      associated tightly with body weight and that heterozygous genotype was a dominant
      genotype, indicating that SNP-29 was a promising marker for MAS.

PMID- 29339743
TI  - A deep study of the protection of Lithium Cobalt Oxide with polymer surface
      modification at 4.5 V high voltage.
AB  - Charging the cells above a conventional voltage of 4.2 V is a promising attempt
      to increase the energy density of Lithium Cobalt Oxide (LCO), however, the
      problem of crystal instability at high voltage that leading deterioration of
      cycle performance needs to be urgently resolved. In this work, as an effective
      and easy approach to improve the cycle performance and crystal stability of LCO
      cycling at 4.5 V high voltage, we demonstrate direct surface modification of a
      LCO cathode by poly [N,N-bis(2-cryano-ethyl)-acrylamide]. The results of SEM, TEM
      and XRD all indicate that the crystal structure of polymer coating LCO remains
      unchanged after cycling at 4.5 V high voltage for 60 times. Furthermore, the XPS
      study of valence of cobalt on the surface of LCO demonstrates that cobaltic ion
      of polymer coating LCO can be reduced to cobaltous ion after charging the cell.
      Thus, the activity of the crystal surface can be weakened, as a result, the
      stability is improved, leading to the performance improvement.

PMID- 29339744
TI  - Human caspase-4 detects tetra-acylated LPS and cytosolic Francisella and
      functions differently from murine caspase-11.
AB  - Caspase-4/5 in humans and caspase-11 in mice bind hexa-acylated lipid A, the
      lipid moeity of lipopolysaccharide (LPS), to induce the activation of non
      canonical inflammasome. Pathogens such as Francisella novicida express an under
      acylated lipid A and escape caspase-11 recognition in mice. Here, we show that
      caspase-4 drives inflammasome responses to F. novicida infection in human
      macrophages. Caspase-4 triggers F. novicida-mediated, gasdermin D-dependent
      pyroptosis and activates the NLRP3 inflammasome. Inflammasome activation could be
      recapitulated by transfection of under-acylated LPS from different bacterial
      species or synthetic tetra-acylated lipid A into cytosol of human macrophage. Our
      results indicate functional differences between human caspase-4 and murine
      caspase-11. We further establish that human Guanylate-binding proteins promote
      inflammasome responses to under-acylated LPS. Altogether, our data demonstrate a
      broader reactivity of caspase-4 to under-acylated LPS than caspase-11, which may
      have important clinical implications for management of sepsis.

PMID- 29339746
TI  - Zika Virus in Salivary Glands of Five Different Species of Wild-Caught Mosquitoes
      from Mexico.
AB  - Zika virus (ZIKV) is a mosquito-borne pathogen, and Aedes aegypti has been
      identified as the main vector of the disease. Other mosquito species in the Aedes
      and Culex genera have been suggested to have the potential for being competent
      vectors based on experimental exposition of mosquitoes to an infectious blood
      meal containing ZIKV. Here, we report the isolation in cell culture of ZIKV
      obtained from different body parts of wild-caught female mosquitoes (Ae. aegypti,
      Ae. vexans, Cx. quinquefasciatus, Cx. coronator, and Cx. tarsalis) and whole male
      mosquitoes (Ae. aegypti and Cx. quinquefasciatus) in Mexico. Importantly, this is
      the first report that shows the presence of the virus in the salivary glands of
      the wild-caught female mosquitoes species, Cx. coronator, Cx. tarsalis, and Ae.
      vexans. Our findings strongly suggest that all the species reported herein are
      potential vectors for ZIKV.

PMID- 29339745
TI  - Genomic and transcriptomic analysis of the Asian honeybee Apis cerana provides
      novel insights into honeybee biology.
AB  - The Asian honeybee Apis cerana is one of two bee species that have been
      commercially kept with immense economic value. Here we present the analysis of
      genomic sequence and transcriptomic exploration for A. cerana as well as the
      comparative genomic analysis of the Asian honeybee and the European honeybee A.
      mellifera. The genome and RNA-seq data yield new insights into the behavioral and
      physiological resistance to the parasitic mite Varroa the evolution of
      antimicrobial peptides, and the genetic basis for labor division in A. cerana.
      Comparison of genes between the two sister species revealed genes specific to A.
      cerana, 54.5% of which have no homology to any known proteins. The observation
      that A. cerana displayed significantly more vigilant grooming behaviors to the
      presence of Varroa than A. mellifera in conjunction with gene expression analysis
      suggests that parasite-defensive grooming in A. cerana is likely triggered not
      only by exogenous stimuli through visual and olfactory detection of the parasite,
      but also by genetically endogenous processes that periodically activates a bout
      of grooming to remove the ectoparasite. This information provides a valuable
      platform to facilitate the traits unique to A. cerana as well as those shared
      with other social bees for health improvement.

PMID- 29339747
TI  - An orthotopic mouse model of gastric cancer invasion and metastasis.
AB  - Gastric cancer is a leading cause of cancer death worldwide, with advanced stage
      being correlated to the level of tumour invasion and metastasis. Current research
      is heavily focused on the identification and development of efficacious
      therapeutics targeting these fundamental hallmarks of cancer, however there are
      currently no animal models that mimic the invasive phenotypes observed in humans.
      To address this we have developed an orthotopic mouse model whereby gastric
      cancer cell lines are tagged with luciferase and injected into the subserosal
      layer of the stomach. This allows for the monitoring of primary tumour growth and
      metastasis in real-time as well as quantitation of the degree of tumour invasion
      through the stomach wall by immunohistochemistry. We have three models based on
      the degree of invasion and metastasis that are cell line specific: The AGS cells
      develop into invasive tumours by 4-weeks with no evidence of metastases, MKN45
      cells are moderately metastatic with minimal invasion till week 2 and MKN28 cells
      are highly metastatic and fully invasive by week 1. These models have utility as
      a tool for testing the efficacy of anti-tumour, anti-invasive and anti-metastatic
      therapies in the setting of gastric cancer, which currently has poor treatment
      options.

PMID- 29339748
TI  - Dot1 regulates nucleosome dynamics by its inherent histone chaperone activity in
      yeast.
AB  - Dot1 (disruptor of telomeric silencing-1, DOT1L in humans) is the only known
      enzyme responsible for histone H3 lysine 79 methylation (H3K79me) and is
      evolutionarily conserved in most eukaryotes. Yeast Dot1p lacks a SET domain and
      does not methylate free histones and thus may have different actions with respect
      to other histone methyltransferases. Here we show that Dot1p displays histone
      chaperone activity and regulates nucleosome dynamics via histone exchange in
      yeast. We show that a methylation-independent function of Dot1p is required for
      the cryptic transcription within transcribed regions seen following disruption of
      the Set2-Rpd3S pathway. Dot1p can assemble core histones to nucleosomes and
      facilitate ATP-dependent chromatin-remodeling activity through its nucleosome
      binding domain, in vitro. Global analysis indicates that Dot1p appears to be
      particularly important for histone exchange and chromatin accessibility on the
      transcribed regions of long-length genes. Our findings collectively suggest that
      Dot1p-mediated histone chaperone activity controls nucleosome dynamics in
      transcribed regions.

PMID- 29339749
TI  - Volatile molecules from bronchoalveolar lavage fluid can 'rule-in' Pseudomonas
      aeruginosa and 'rule-out' Staphylococcus aureus infections in cystic fibrosis
      patients.
AB  - Respiratory infections caused by Pseudomonas aeruginosa and Staphylococcus aureus
      are the leading cause of morbidity and mortality in cystic fibrosis (CF)
      patients. The authors aimed to identify volatile biomarkers from bronchoalveolar
      lavage (BAL) samples that can guide breath biomarker development for pathogen
      identification. BAL samples (n = 154) from CF patients were analyzed using two
      dimensional gas chromatography time-of-flight mass spectrometry. Random Forest
      was used to select suites of volatiles for identifying P. aeruginosa-positive and
      S. aureus-positive samples using multiple infection scenarios and validated using
      test sets. Using nine volatile molecules, we differentiated P. aeruginosa
      positive (n = 7) from P. aeruginosa-negative (n = 53) samples with an area under
      the receiver operating characteristic curve (AUROC) of 0.86 (95% CI 0.71-1.00)
      and with positive and negative predictive values of 0.67 (95% CI 0.38-0.75) and
      0.92 (95% CI 0.88-1.00), respectively. We were also able to discriminate S.
      aureus-positive (n = 15) from S. aureus-negative (n = 45) samples with an AUROC
      of 0.88 (95% CI 0.79-1.00) using eight volatiles and with positive and negative
      predictive values of 0.86 (95% CI 0.61-0.96) and 0.70 (95% CI 0.61-0.75),
      respectively. Prospective validation of identified biomarkers as screening tools
      in patient breath may lead to clinical application.

PMID- 29339750
TI  - A Single Dose of Modified Vaccinia Ankara expressing Ebola Virus Like Particles
      Protects Nonhuman Primates from Lethal Ebola Virus Challenge.
AB  - Ebola virus (EBOV), isolate Makona, was the causative agent of the West African
      epidemic devastating predominantly Guinea, Liberia and Sierra Leone from 2013
      2016. While several experimental vaccine and treatment approaches have been
      accelerated through human clinical trials, there is still no approved
      countermeasure available against this disease. Here, we report the construction
      and preclinical efficacy testing of a novel recombinant modified vaccinia Ankara
      (MVA)-based vaccine expressing the EBOV-Makona glycoprotein GP and matrix protein
      VP40 (MVA-EBOV). GP and VP40 form EBOV-like particles and elicit protective
      immune responses. In this study, we report 100% protection against lethal EBOV
      infection in guinea pigs after prime/boost vaccination with MVA-EBOV.
      Furthermore, this MVA-EBOV protected macaques from lethal disease after a single
      dose or prime/boost vaccination. The vaccine elicited a variety of antibody
      responses to both antigens, including neutralizing antibodies and antibodies with
      antibody-dependent cellular cytotoxic activity specific for GP. This is the first
      report that a replication-deficient MVA vector can confer full protection against
      lethal EBOV challenge after a single dose vaccination in macaques.

PMID- 29339751
TI  - JmjC domain proteins modulate circadian behaviors and sleep in Drosophila.
AB  - Jumonji (JmjC) domain proteins are known regulators of gene expression and
      chromatin organization by way of histone demethylation. Chromatin modification
      and remodeling provides a means to modulate the activity of large numbers of
      genes, but the importance of this class of predicted histone-modifying enzymes
      for different aspects of post-developmental processes remains poorly understood.
      Here we test the function of all 11 non-lethal members in the regulation of
      circadian rhythms and sleep. We find loss of every Drosophila JmjC gene affects
      different aspects of circadian behavior and sleep in a specific manner. Together
      these findings suggest that the majority of JmjC proteins function as regulators
      of behavior, rather than controlling essential developmental programs.

PMID- 29339752
TI  - Prognostic Performance of Ten Liver Function Models in Patients with
      Hepatocellular Carcinoma Undergoing Radiofrequency Ablation.
AB  - Liver functional capacity is a crucial survival determinant for hepatocellular
      carcinoma (HCC). Noninvasive models were proposed to assess hepatic reserve, but
      their performance in outcome prediction is unclear. We aimed to investigate 10
      currently used liver function models in HCC patients undergoing radiofrequency
      ablation (RFA). A total 499 HCC patients were prospectively identified.
      Homogeneity and corrected Akaike information criteria (AICc) were compared. Cox
      proportional hazards model was used to identify independent survival predictors.
      Significance survival differences were found across 10 noninvasive models (all p
      < 0.001) except for GUCI and APRI grade 2 vs 3, and King's score grade 1 vs 2.
      Among these models, ALBI grade showed the highest homogeneity and lowest AICs
      value, indicating a better prognostic performance. Within Child-Turcotte-Pugh
      (CTP) score 5 group, significant survival difference was demonstrated between
      ALBI grade 1 and 2 (p < 0.001); for those with CTP score 6 or higher, only ALBI
      grade 2 and 3 showed survival difference (p < 0.001). Cox analysis disclosed that
      ALBI grade, tumor size and performance status were independent prognostic
      predictors. There was significant correlation between CTP score and other 9
      models. We conclude that ALBI grade may serve as objective and feasible surrogate
      for prognostic prediction in HCC patients undergoing RFA.

PMID- 29339753
TI  - Efficient isolation on Vero.DogSLAMtag cells and full genome characterization of
      Dolphin Morbillivirus (DMV) by next generation sequencing.
AB  - The Dolphin Morbillivirus (DMV) genome from the first Mediterranean epidemic
      (1990-'92) is the only cetacean Morbillivirus that has been completely sequenced.
      Here, we report the first application of next generation sequencing (NGS) to
      morbillivirus infection of aquatic mammals. A viral isolate, representative of
      the 2006-'08 Mediterranean epidemic (DMV_IZSPLV_2008), efficiently grew on
      Vero.DogSLAMtag cells and was submitted to whole genome characterization by NGS.
      The final genome length was 15,673 nucleotides, covering 99.82% of the DMV
      reference genome. Comparison of DMV_IZSPLV_2008 and 1990-'92 DMV strain sequences
      revealed 157 nucleotide mutations and 47 amino acid changes. The sequence
      similarity was 98.7% at the full genome level. Whole-genome phylogeny suggested
      that the DMV strain circulating during the 2006-'08 epidemics emerged from the
      1990-'92 DMV strain. Viral isolation is considered the "gold standard" for
      morbillivirus diagnostics but efficient propagation of infectious virus is
      difficult to achieve. The successful cell replication of this strain allowed
      performing NGS directly from the viral RNA, without prior PCR amplification. We
      therefore provide to the scientific community a second DMV genome, representative
      of another major outbreak. Interestingly, genome comparison revealed that the
      neglected L gene encompasses 74% of the genetic diversity and might serve as
      "hypervariable" target for strain characterization.

PMID- 29339754
TI  - Baicalin modulates NF-kappaB and NLRP3 inflammasome signaling in porcine aortic
      vascular endothelial cells Infected by Haemophilus parasuis Causing Glasser's
      disease.
AB  - Haemophilus parasuis (H. parasuis) can cause vascular inflammatory injury, but
      the molecular basis of this effect remains unclear. In this study,we investigated
      the effect of the anti-inflammatory, anti-microbial and anti-oxidant agent,
      baicalin, on the nuclear factor (NF)-kappaB and NLRP3 inflammasome signaling
      pathway in pig primary aortic vascular endothelial cells. Activation of the NF
      kappaB and NLRP3 inflammasome signaling pathway was induced in H. parasuis
      infected cells. However, baicalin reduced the production of reactive oxygen
      species, apoptosis, and activation of the NF-kappaB and NLRP3 inflammasome
      signaling pathway in infected cells. These results revealed that baicalin can
      inhibit H. parasuis-induced inflammatory responses in porcine aortic vascular
      endothelial cells, and may thus offer a novel strategy for controlling and
      treating H. parasuis infection. Furthermore, the results suggest that piglet
      primary aortic vascular endothelial cells may provide an experimental model for
      future studies of H. parasuis infection.

PMID- 29339755
TI  - A prebiotic template-directed peptide synthesis based on amyloids.
AB  - The prebiotic replication of information-coding molecules is a central problem
      concerning life's origins. Here, we report that amyloids composed of short
      peptides can direct the sequence-selective, regioselective and stereoselective
      condensation of amino acids. The addition of activated DL-arginine and DL
      phenylalanine to the peptide RFRFR-NH2 in the presence of the complementary
      template peptide Ac-FEFEFEFE-NH2 yields the isotactic product FRFRFRFR-NH2, 1 of
      64 possible triple addition products, under conditions in which the absence of
      template yields only single and double additions of mixed stereochemistry. The
      templating mechanism appears to be general in that a different amyloid formed by
      (Orn)V(Orn)V(Orn)V(Orn)V-NH2 and Ac-VDVDVDVDV-NH2 is regioselective and
      stereoselective for N-terminal, L-amino-acid addition while the ornithine-valine
      peptide alone yields predominantly sidechain condensation products with little
      stereoselectivity. Furthermore, the templating reaction is stable over a wide
      range of pH (5.6-8.6), salt concentration (0-4 M NaCl), and temperature (25-90 
      degrees C), making the amyloid an attractive model for a prebiotic peptide
      replicating system.

PMID- 29339756
TI  - Shot-by-shot characterization of focused X-ray free electron laser pulses.
AB  - X-ray free electron lasers (XFEL) provide intense and almost coherent X-ray
      pulses. They are used for various experiments investigating physical and chemical
      properties in materials and biological science because of their complete
      coherence, high intensity, and very short pulse width. In XFEL experiments,
      specimens are irradiated by XFEL pulses focused by mirror optics. The focused
      pulse is too intense to measure its coherence by placing an X-ray detector on the
      focal spot. Previously, a method was proposed for evaluating the coherence of
      focused pulses from the visibility of the diffraction intensity of colloidal
      particles by the speckle visibility spectroscopy (SVS). However, the visibility
      cannot be determined exactly because the diffraction intensity is integrated into
      each finite size detector pixel. Here, we propose a method to evaluate the
      coherence of each XFEL pulse by using SVS in combination with a theory for exact
      sampling of the diffraction pattern and a technique of multiplying the
      diffraction data by a Gaussian masks, which reduces the influence of data missing
      in small-angle regions due to the presence of a direct beamstop. We also
      introduce a method for characterizing the shot-by-shot size of each XFEL pulse by
      analysing the X-ray irradiated area.

PMID- 29339757
TI  - Melatonin increases chilling tolerance in postharvest peach fruit by alleviating
      oxidative damage.
AB  - Melatonin has been reported to alleviate chilling symptoms in postharvest peach
      fruit during cold storage, however, the mechanism involved is largely unknown. To
      better understand its role in chilling tolerance, here we investigated the
      effects of melatonin on oxidative damage in peach fruit subjected to chilling
      after harvest. Chilling injury of peaches was dramatically reduced by melatonin
      treatment. Melatonin induced hydrogen peroxide (H2O2) content at the early stage
      of storage but inhibited its accumulation thereafter. Meanwhile, melatonin also
      up-regulated the expression of genes involved in antioxidant responses in
      peaches. In addition, compared to the control fruit, peaches treated with
      melatonin displayed higher transcript abundance of ascorbic acid (AsA)
      biosynthetic genes and consequently increased the AsA content. Our results
      suggested that in response to melatonin during chilling, the high H2O2 level in
      the treated peaches at the initial time of storage, may work as a signaling
      molecule to induce protective mechanisms via up-regulating the expression of
      antioxidative genes and increasing AsA content. On the other hand, after the
      transient increase in the treated peaches, H2O2 was efficiently removed because
      of the activated antioxidant systems, which was associated with the higher
      chilling tolerance induced by melatonin.

PMID- 29339758
TI  - MiRNA-seq-based profiles of miRNAs in mulberry phloem sap provide insight into
      the pathogenic mechanisms of mulberry yellow dwarf disease.
AB  - A wide range of miRNAs have been identified as phloem-mobile molecules that play
      important roles in coordinating plant development and physiology. Phytoplasmas
      are associated with hundreds of plant diseases, and the pathogenesis involved in
      the interactions between phytoplasmas and plants is still poorly understood. To
      analyse the molecular mechanisms of phytoplasma pathogenicity, the miRNAs
      profiles in mulberry phloem saps were examined in response to phytoplasma
      infection. A total of 86 conserved miRNAs and 19 novel miRNAs were identified,
      and 30 conserved miRNAs and 13 novel miRNAs were differentially expressed upon
      infection with phytoplasmas. The target genes of the differentially expressed
      miRNAs are involved in diverse signalling pathways showing the complex
      interactions between mulberry and phytoplasma. Interestingly, we found that mul
      miR482a-5p was up-regulated in the infected phloem saps, and grafting experiments
      showed that it can be transported from scions to rootstock. Based on the results,
      the complexity and roles of the miRNAs in phloem sap and the potential molecular
      mechanisms of their changes were discussed. It is likely that the phytoplasma
      responsive miRNAs in the phloem sap modulate multiple pathways and work
      cooperatively in response to phytoplasma infection, and their expression changes
      may be responsible for some symptoms in the infected plants.

PMID- 29339759
TI  - Optimized chaotic Brillouin dynamic grating with filtered optical feedback.
AB  - Chaotic Brillouin dynamic gratings (BDGs) have special advantages such as the
      creation of single, permanent and localized BDG. However, the periodic signals
      induced by conventional optical feedback (COF) in chaotic semiconductor lasers
      can lead to the generation of spurious BDGs, which will limit the application of
      chaotic BDGs. In this paper, filtered optical feedback (FOF) is proposed to
      eliminate spurious BDGs. By controlling the spectral width of the optical filter
      and its detuning from the laser frequency, semiconductor lasers with FOF operate
      in the suppression region of the time-delay signature, and chaotic outputs
      serving as pump waves are then utilized to generate the chaotic BDG in a
      polarization maintaining fiber. Through comparative analysis of the COF and FOF
      schemes, it has been demonstrated that spurious BDGs are effectively eliminated
      and that the reflection characterization of the chaotic BDG is improved. The
      influence of FOF on the reflection and gain spectra of the chaotic BDG is
      analyzed as well.

PMID- 29339760
TI  - Biochemical and genetic characterization of a novel metallo-beta-lactamase from
      marine bacterium Erythrobacter litoralis HTCC 2594.
AB  - Metallo-beta-lactamases (MBLs) are a group of enzymes that can inactivate most
      commonly used beta-lactam-based antibiotics. Among MBLs, New Delhi metallo-beta
      lactamase-1 (NDM-1) constitutes an urgent threat to public health as evidenced by
      its success in rapidly disseminating worldwide since its first discovery. Here we
      report the biochemical and genetic characteristics of a novel MBL, ElBla2, from
      the marine bacterium Erythrobacter litoralis HTCC 2594. This enzyme has a higher
      amino acid sequence similarity to NDM-1 (56%) than any previously reported MBL.
      Enzymatic assays and secondary structure alignment also confirmed the high
      similarity between these two enzymes. Whole genome comparison of four
      Erythrobacter species showed that genes located upstream and downstream of elbla2
      were highly conserved, which may indicate that elbla2 was lost during evolution.
      Furthermore, we predicted two prophages, 13 genomic islands and 25 open reading
      frames related to insertion sequences in the genome of E. litoralis HTCC 2594.
      However, unlike NDM-1, the chromosome encoded ElBla2 did not locate in or near
      these mobile genetic elements, indicating that it cannot transfer between
      strains. Finally, following our phylogenetic analysis, we suggest a
      reclassification of E. litoralis HTCC 2594 as a novel species: Erythrobacter sp.
      HTCC 2594.

PMID- 29339761
TI  - New virulence factor CSK29544_02616 as LpxA binding partner in Cronobacter
      sakazakii.
AB  - Cronobacter sakazakii is an opportunistic pathogen that can cause meningitis and
      necrotizing enterocolitis in premature infants, but its virulence determinants
      remain largely unknown. In this study, a transposon-mediated random-mutant
      library of C. sakazakii was used to identify new virulence factors. Compared to
      wild-type bacteria, a mutant lacking CSK29544_02616 (referred to as labp) was
      defective in invasion into intestinal epithelial cells (by at least 1000-fold)
      and showed less phagocytosis by macrophages (by at least 50-fold). The lack of
      labp in C. sakazakii changed the profile of outer membrane proteins, decreased
      the production of lipopolysaccharides, and increased the production of membrane
      phospholipids. Bacterial physiological characteristics including surface
      hydrophobicity and motility were also altered in the absence of labp, presumably
      because of changes in the bacterial-envelope structure. To systematically
      determine the role of labp, ligand fishing was conducted using Labp as a bait,
      which revealed LpxA as a binding partner of Labp. LpxA is UDP-N-acetylglucosamine
      (GlcNAc) acyltransferase, the first enzyme in the pathway of lipid A
      biosynthesis. Labp increased the enzymatic activity of LpxA without influencing
      lpxA expression. Considering multifaceted roles of lipopolysaccharides in
      virulence regulation, Labp is a novel virulence factor that promotes the
      production of lipid A by LpxA in Cronobacter.

PMID- 29339764
TI  - Four-dimensional entanglement distribution over 100 km.
AB  - High-dimensional quantum entanglement can enrich the functionality of quantum
      information processing. For example, it can enhance the channel capacity for
      linear optic superdense coding and decrease the error rate threshold of quantum
      key distribution. Long-distance distribution of a high-dimensional entanglement
      is essential for such advanced quantum communications over a communications
      network. Here, we show a long-distance distribution of a four-dimensional
      entanglement. We employ time-bin entanglement, which is suitable for a fibre
      transmission, and implement scalable measurements for the high-dimensional
      entanglement using cascaded Mach-Zehnder interferometers. We observe that a pair
      of time-bin entangled photons has more than 1 bit of secure information capacity
      over 100 km. Our work constitutes an important step towards secure and dense
      quantum communications in a large Hilbert space.

PMID- 29339762
TI  - Supra-pharmacological concentration of capsaicin stimulates brown adipogenesis
      through induction of endoplasmic reticulum stress.
AB  - We previously showed that brown (pre)adipocytes express Trpv1, a capsaicin
      receptor, and that capsaicin stimulates differentiation of brown preadipocytes in
      the late stages of brown adipogenesis. The present study revealed that treatment
      with 100 MUM capsaicin stimulates brown adipogenesis by inducing endoplasmic
      reticulum (ER) stress. Treatment with capsaicin (100 MUM) during brown
      adipogenesis enhanced lipid accumulation and the expression of Ucp1, a gene
      selectively expressed in brown adipocytes. Capsaicin treatment also caused an
      increase in the cytosolic calcium concentration even when extracellular calcium
      was removed. I-RTX, a Trpv1 inhibitor, did not modulate the increase in cytosolic
      calcium concentration, lipid accumulation or Ucp1 expression. Previous studies
      revealed that the release of calcium from the ER induces ER stress, leading to
      the conversion of X-box binding protein 1 (Xbp1) pre-mRNA to spliced Xbp1 (sXbp1)
      as well as the up-regulation of Chop expression. Capsaicin treatment increased
      the expression of sXbp1 and Chop in brown preadipocytes and did not enhance lipid
      accumulation or Ucp1 expression in Xbp1 knockdown cells. The present results
      describe a novel mechanism of brown adipogenesis regulation via ER stress that is
      induced by a supra-pharmacological concentration of capsaicin.

PMID- 29339763
TI  - Glucocorticoid receptor GRbeta regulates glucocorticoid-induced ocular
      hypertension in mice.
AB  - Prolonged glucocorticoid (GC) therapy can cause GC-induced ocular hypertension
      (OHT), which if left untreated progresses to iatrogenic glaucoma and permanent
      vision loss. The alternatively spliced isoform of glucocorticoid receptor GRbeta
      acts as dominant negative regulator of GR activity, and it has been shown that
      overexpressing GRbeta in trabecular meshwork (TM) cells inhibits GC-induced
      glaucomatous damage in TM cells. The purpose of this study was to use viral
      vectors to selectively overexpress the GRbeta isoform in the TM of mouse eyes
      treated with GCs, to precisely dissect the role of GRbeta in regulating steroid
      responsiveness. We show that overexpression of GRbeta inhibits GC effects on MTM
      cells in vitro and GC-induced OHT in mouse eyes in vivo. Ad5 mediated GRbeta
      overexpression reduced the GC induction of fibronectin, collagen 1, and myocilin
      in TM of mouse eyes both in vitro and in vivo. GRbeta also reversed DEX-Ac
      induced IOP elevation, which correlated with increased conventional aqueous humor
      outflow facility. Thus, GRbeta overexpression reduces effects caused by GCs and
      makes cells more resistant to GC treatment. In conclusion, our current work
      provides the first evidence of the in vivo physiological role of GRbeta in
      regulating GC-OHT and GC-mediated gene expression in the TM.

PMID- 29339765
TI  - Mutations in bassoon in individuals with familial and sporadic progressive
      supranuclear palsy-like syndrome.
AB  - Clinical diagnosis of progressive supranuclear palsy (PSP) is sometimes difficult
      because various phenotypes have been identified. Here, we report a mutation in
      the bassoon (BSN) gene in a family with PSP-like syndrome. Their clinical
      features resembled not only those of PSP patients but also those of individuals
      with multiple system atrophy and Alzheimer's disease. The neuropathological
      findings showed a novel three + four repeat tauopathy with pallido-luysio-nigral
      degeneration and hippocampal sclerosis. Whole-exome analysis of this family
      identified a novel missense mutation in BSN. Within the pedigree, the detected
      BSN mutation was found only in affected individuals. Further genetic analyses
      were conducted in probands from four other pedigrees with PSP-like syndrome and
      in 41 sporadic cases. Three missense mutations in BSN that are very rarely listed
      in databases of healthy subjects were found in four sporadic cases. Western blot
      analysis of tau following the overexpression of wild-type or mutated BSN revealed
      the possibility that wild-type BSN reduced tau accumulation, while mutated BSN
      lost this function. An association between BSN and neurological diseases has not
      been previously reported. Our results revealed that the neurodegenerative
      disorder associated with the original proband's pedigree is a novel tauopathy,
      differing from known dementia and parkinsonism syndromes, including PSP.

PMID- 29339766
TI  - The crystal structure of D-xylonate dehydratase reveals functional features of
      enzymes from the Ilv/ED dehydratase family.
AB  - The Ilv/ED dehydratase protein family includes dihydroxy acid-, gluconate-, 6
      phosphogluconate- and pentonate dehydratases. The members of this family are
      involved in various biosynthetic and carbohydrate metabolic pathways. Here, we
      describe the first crystal structure of D-xylonate dehydratase from Caulobacter
      crescentus (CcXyDHT) at 2.7 A resolution and compare it with other available
      enzyme structures from the IlvD/EDD protein family. The quaternary structure of
      CcXyDHT is a tetramer, and each monomer is composed of two domains in which the N
      terminal domain forms a binding site for a [2Fe-2S] cluster and a Mg2+ ion. The
      active site is located at the monomer-monomer interface and contains residues
      from both the N-terminal recognition helix and the C-terminus of the dimeric
      counterpart. The active site also contains a conserved Ser490, which probably
      acts as a base in catalysis. Importantly, the cysteines that participate in the
      binding and formation of the [2Fe-2S] cluster are not all conserved within the
      Ilv/ED dehydratase family, which suggests that some members of the IlvD/EDD
      family may bind different types of [Fe-S] clusters.

PMID- 29339767
TI  - Regulatory T cells trigger effector T cell DNA damage and senescence caused by
      metabolic competition.
AB  - Defining the suppressive mechanisms used by regulatory T (Treg) cells is critical
      for the development of effective strategies for treating tumors and chronic
      infections. The molecular processes that occur in responder T cells that are
      suppressed by Treg cells are unclear. Here we show that human Treg cells initiate
      DNA damage in effector T cells caused by metabolic competition during cross-talk,
      resulting in senescence and functional changes that are molecularly distinct from
      anergy and exhaustion. ERK1/2 and p38 signaling cooperate with STAT1 and STAT3 to
      control Treg-induced effector T-cell senescence. Human Treg-induced T-cell
      senescence can be prevented via inhibition of the DNA damage response and/or STAT
      signaling in T-cell adoptive transfer mouse models. These studies identify
      molecular mechanisms of human Treg cell suppression and indicate that targeting
      Treg-induced T-cell senescence is a checkpoint for immunotherapy against cancer
      and other diseases associated with Treg cells.

PMID- 29339768
TI  - The characterization of the circadian clock in the olive fly Bactrocera oleae
      (Diptera: Tephritidae) reveals a Drosophila-like organization.
AB  - The olive fruit fly, Bactrocera oleae, is the single most important pest for the
      majority of olive plantations. Oxitec's self-limiting olive fly technology
      (OX3097D-Bol) offers an alternative management approach to this insect pest.
      Because of previously reported asynchrony in the mating time of wild and
      laboratory strains, we have characterized the olive fly circadian clock applying
      molecular, evolutionary, anatomical and behavioural approaches. Here we
      demonstrate that the olive fly clock relies on a Drosophila melanogaster-like
      organization and that OX3097D-Bol carries a functional clock similar to wild-type
      strains, confirming its suitability for operational use.

PMID- 29339769
TI  - Universal Transient Dynamics of Electrowetting Droplets.
AB  - Droplet spreading on substrates by electrowetting exhibits either of the two
      transient behaviours: one characterised by contact line oscillation, and the
      other one by slow spreading dynamics. The transition between these behaviours
      remains elusive due to the current limited understanding of the spreading
      dynamics on the hydrodynamical and electrical properties of electrowetting
      systems. To understand this transition we propose a model capturing the
      transition's occurrence based on both the hydrodynamical and electrical
      parameters. We derive the critical viscosity at which the transition occurs and
      reveal its subtle and often hidden dependence on the electrowetting dynamics. We
      find and experimentally verify that the condition for minimization of droplets'
      actuation time is only achieved at the transition. Particularly, the transition
      time as a function of damping ratio exhibits the general feature of Kramers'
      reaction-rate theory.

PMID- 29339770
TI  - Reversing Cocaine-Induced Adaptations and Reducing Relapse: An Opportunity for
      Repurposing Riluzole.

PMID- 29339771
TI  - Etiology of language network changes during recovery of aphasia after stroke.
AB  - Knowledge of spatiotemporal patterns of language network changes may help in
      predicting outcome in aphasic stroke patients. Here we assessed language function
      and performed functional MRI four times during one year to measure language
      network activation and cerebrovascular reactivity (with breath-holding) in twelve
      left-hemispheric stroke patients, of whom two dropped out before the final
      measurement, and eight age-matched controls. Language outcome was related to
      increase of activation in left and right posterior inferior temporal gyrus over
      the first year, while activation increase in right inferior frontal gyrus was
      inversely correlated to language recovery. Outcome prediction improved by
      addition of early language-induced activation of the left posterior inferior
      temporal gyrus to a regression model with baseline language performance as first
      predictor. Variations in language-induced activation in right inferior frontal
      gyrus were primarily related to differences in vascular reactivity. Furthermore,
      several language-activation changes could not be linked to alterations in
      language proficiency nor vascular reactivity, and were assumed to be caused by
      unspecified intersession variability. In conclusion, early functional
      neuroimaging improves outcome prediction of aphasia after stroke. Controlling for
      cerebrovascular reactivity and unspecified intersession variability may result in
      more accurate assessment of the relationship between activation pattern shifts
      and function after stroke.

PMID- 29339772
TI  - Foxo1 Promotes Th9 Cell Differentiation and Airway Allergy.
AB  - T helper 9 (Th9) cells are effector CD4+ T cells that are characterized by the
      production of interleukin-9 (IL-9) and have been associated with allergic
      responses. Here, we found that the expression of the transcription factor
      forkhead box O1 (Foxo1) was induced in Th9 and Foxo1 plays a crucial role in the
      differentiation of Th9 cells. Pharmacological inhibition of Foxo1 or genetic
      disruption of Foxo1 in CD4+ T cells caused a reduction in IL-9 expression while
      upregulating IL-17A and IFNgamma production. Furthermore, chromatin
      immunoprecipitation (ChIP) followed by luciferase assays revealed direct binding
      of Foxo1 to both the Il9 and Irf4 promoters and induces their transactivation.
      Lastly, adoptive transfer of Th9 cells into lungs induced asthma-like symptoms
      that were ameliorated by Foxo1 inhibitor, AS1842856. Together, our findings
      demonstrate a novel regulator of Th9 cells with a direct implication in allergic
      inflammation.

PMID- 29339774
TI  - Erratum: Sensory augmentation: integration of an auditory compass signal into
      human perception of space.
AB  - This corrects the article DOI: 10.1038/srep42197.

PMID- 29339773
TI  - Postural adaptations to unilateral knee joint hypomobility induced by orthosis
      wear during gait initiation.
AB  - Balance control and whole-body progression during gait initiation (GI) involve
      knee-joint mobility. Single knee-joint hypomobility often occurs with aging,
      orthopedics or neurological conditions. The goal of the present study was to
      investigate the capacity of the CNS to adapt GI organization to single knee-joint
      hypomobility induced by the wear of an orthosis. Twenty-seven healthy adults
      performed a GI series on a force-plate in the following conditions: without
      orthosis ("control"), with knee orthosis over the swing leg ("orth-swing") and
      with the orthosis over the contralateral stance leg ("orth-stance"). In orth
      swing, amplitude of mediolateral anticipatory postural adjustments (APAs) and
      step width were larger, execution phase duration longer, and anteroposterior APAs
      smaller than in control. In orth-stance, mediolateral APAs duration was longer,
      step width larger, and amplitude of anteroposterior APAs smaller than in control.
      Consequently, step length and progression velocity (which relate to the "motor
      performance") were reduced whereas stability was enhanced compared to control.
      Vertical force impact at foot-contact did not change across conditions, despite a
      smaller step length in orthosis conditions compared to control. These results
      show that the application of a local mechanical constraint induced profound
      changes in the global GI organization, altering motor performance but ensuring
      greater stability.

PMID- 29339775
TI  - Anti-apoptotic A1 is not essential for lymphoma development in Eu-Myc mice but
      helps sustain transplanted Eu-Myc tumour cells.
AB  - The transcription factor c-MYC regulates a multiplicity of genes involved in
      cellular growth, proliferation, metabolism and DNA damage response and its
      overexpression is a hallmark of many tumours. Since MYC promotes apoptosis under
      conditions of stress, such as limited availability of nutrients or cytokines, MYC
      driven cells are very much dependent on signals that inhibit cell death. Stress
      signals trigger apoptosis via the pathway regulated by opposing fractions of the
      BCL-2 protein family and previous genetic studies have shown that the development
      of B lymphoid tumours in Eu-Myc mice is critically dependent on expression of pro
      survival BCL-2 relatives MCL-1, BCL-W and, to a lesser extent, BCL-XL, but not
      BCL-2 itself, and that sustained growth of these lymphomas is dependent on MCL-1.
      Using recently developed mice that lack expression of all three functional pro
      survival A1 genes, we show here that the kinetics of lymphoma development in Eu
      Myc mice and the competitive repopulation capacity of Eu-Myc haemopoietic stem
      and progenitor cells is unaffected by the absence of A1. However, conditional
      loss of a single remaining functional A1 gene from transplanted A1-a-/-A1-b fl/fl
      A1-c-/- Eu-Myc lymphomas slowed their expansion, significantly extending the life
      of the transplant recipients. Thus, A1 contributes to the survival of malignant
      Eu-Myc-driven B lymphoid cells. These results strengthen the case for BFL-1, the
      human homologue of A1, being a valid target for drug development for MYC-driven
      tumours.

PMID- 29339776
TI  - The experience of spasticity after spinal cord injury: perceived characteristics
      and impact on daily life.
AB  - STUDY DESIGN: Cross-sectional survey. OBJECTIVES: Determine the impact of motor
      control characteristics attributed to spasticity, such as spasms, stiffness, and
      clonus on the daily life of people with spinal cord injury (SCI). SETTING:
      Nationwide, United States. METHODS: Internet-administered questionnaire, the
      Patient Reported Impact of Spasticity Measure (PRISM) and items describing
      characteristics of spasticity including stiffness, spasms, clonus, and pain.
      RESULTS: Of the 145 respondents, 113 (78%) reported a PRISM score of at least
      5/164, indicating spasticity had some impact on their daily lives. Stiffness
      impact was highly correlated (rho = 0.84; p < 0.01) with the PRISM negative
      impact on Daily Activities subscale and moderately correlated with the other
      PRISM subscales (rho = 0.55-0.63; p < 0.01). Spasm presence had a negligible or
      low correlation with PRISM negative impact subscales (rho = 0.29-0.47; p < 0.01).
      Trunk muscle stiffness and spasms had a low correlation with PRISM Need for
      Assistance and Daily activities (rho = 0.42 and rho = 0.41, p < 0.01,
      respectively). Anti-spasticity medications were ineffective for 58% of
      respondents. Pain in the legs was reported by 57% of respondents. CONCLUSIONS:
      The experience of spasticity is highly individualized, and is often distributed
      differently across arms, trunk, and legs. Despite the fact that traditional
      definitions of spasticity focus on reflex responsiveness, the stiffness
      associated with spasticity appears to be more problematic than spasms or clonus.
      The self-described characteristics of spasticity and its physiological
      presentation are complex and related to pain. This varied presentation lends
      support to the concept that management of spasticity may be best achieved by
      multimodality strategies.

PMID- 29339777
TI  - Regulation of the Response of Caenorhabditis elegans to Simulated Microgravity by
      p38 Mitogen-Activated Protein Kinase Signaling.
AB  - The in vivo function of p38 mitogen-activated protein kinase (MAPK) signaling in
      regulating the response to simulated microgravity is still largely unclear. Using
      Caenorhabditis elegans as an assay system, we investigated the in vivo function
      of p38 MAPK signaling in regulating the response of animals to simulated
      microgravity and the underlying molecular mechanism. Simulated microgravity
      treatment significantly increased the transcriptional expressions of genes (pmk
      1, sek-1, and nsy-1) encoding core p38 MAPK signaling pathway and the expression
      of phosphorylated PMK-1/p38 MAPK. The pmk-1, sek-1, or nsy-1 mutant was
      susceptible to adverse effects of simulated microgravity. The intestine-specific
      activity of PMK-1 was required for its function in regulating the response to
      simulated microgravity, and the entire p38 MAPK signaling pathway could act in
      the intestine to regulate the response to simulated microgravity. In the
      intestine, SKN-1 and ATF-7, two transcriptional factors, were identified as
      downstream targets for PMK-1 in regulating the response to simulated
      microgravity. Therefore, the activation of p38 MAPK signaling may mediate a
      protection mechanism for nematodes against the adverse effects of simulated
      microgravity. Additionally, our results highlight the potential crucial role of
      intestinal cells in response to simulated microgravity in nematodes.

PMID- 29339778
TI  - A novel human muscle cell model of Duchenne muscular dystrophy created by
      CRISPR/Cas9 and evaluation of antisense-mediated exon skipping.
AB  - Oligonucleotide-mediated splicing modulation is a promising therapeutic approach
      for Duchenne muscular dystrophy (DMD). Recently, eteplirsen, a phosphorodiamidate
      morpholino oligomer-based splice-switching oligonucleotide (SSO) targeting DMD
      exon 51, was approved by the U.S. Food and Drug Administration as the first
      antisense-based drug for DMD patients. For further exploring SSOs targeting other
      exons in the DMD gene, the efficacy of exon skipping and protein rescue with each
      SSO sequence needs evaluations in vitro. However, only a few immortalized muscle
      cell lines derived from DMD patients have been reported and are available to test
      the efficacy of exon skipping in vitro. To solve this problem, we generated a
      novel immortalized DMD muscle cell line from the human rhabdomyosarcoma (RD) cell
      line. We removed DMD exons 51-57 (~0.3 Mb) in the RD cell line using the
      CRISPR/Cas9 system. Additionally, in this DMD model cell line, we evaluated the
      exon 50 skipping activity of previously reported SSOs at both the mRNA and
      protein levels. CRISPR/Cas9-mediated gene editing of the DMD gene in the RD cell
      line will allow for assessment of SSOs targeting most of the rare mutations in
      the DMD gene.

PMID- 29339779
TI  - Novel recessive mutations in MSTO1 cause cerebellar atrophy with pigmentary
      retinopathy.
AB  - Misato 1, mitochondrial distribution and morphology regulator (encoded by the
      MSTO1 gene), is involved in mitochondrial distribution and morphology. Recently,
      MSTO1 mutations have been shown to cause clinical manifestations suggestive of
      mitochondrial dysfunction, such as muscle weakness, short stature, motor
      developmental delay, and cerebellar atrophy. Both autosomal dominant and
      recessive modes of inheritance have been suggested. We performed whole-exome
      sequencing in two unrelated patients showing cerebellar atrophy, intellectual
      disability, and pigmentary retinopathy. Three novel mutations were identified:
      c.836 G > A (p.Arg279His), c.1099-1 G > A (p.Val367Trpfs*2), and c.79 C > T
      (p.Gln27*). Both patients had compound heterozygous mutations with a combination
      of protein-truncation mutation and missense mutation, the latter shared by them
      both. This survey of two patients with recessive and novel MSTO1 mutations
      provides additional clinical and genetic information on the pathogenicity of
      MSTO1 in humans.

PMID- 29339780
TI  - Extractable pool of biochar controls on crop productivity rather than greenhouse
      gas emission from a rice paddy under rice-wheat rotation.
AB  - The role of extractable pool of biochar in crop productivity and soil greenhouse
      gas (GHGs) emission is not yet clear. In this study, two biochars with and
      without extraction was added to a paddy before rice transplantation at 20 t.ha-1.
      Crop yield, plant traits and greenhouse gas emission monitored throughout a rice
      wheat rotation. Between the biochar treatments, changes in bulk density and
      microbial biomass carbon were insignificant. However, the increase in organic
      carbon was similar between maize and wheat biochars while higher under bulk wheat
      biochar than extracted one. The increase in available P and K was higher under
      wheat than maize biochar regardless of extraction. Moreover, the increase in
      plant traits and grain yield, in rice season only, was higher under bulk than
      extracted biochars. Yet, there was no difference in changes in GHGs emission
      between bulk and extracted biochars regardless of feedstock. Nevertheless,
      increased methane emission for rice season was lower under extracted biochars
      than bulk ones. Overall, crop productivity rather than GHGs emission was affected
      by treatment of extraction of biochars. Thus, use of unextracted biochar is
      recommended for improving soil crop productivity in the paddy soils.

PMID- 29339781
TI  - Draxin regulates hippocampal neurogenesis in the postnatal dentate gyrus by
      inhibiting DCC-induced apoptosis.
AB  - Hippocampal neurogenesis in the dentate gyrus (DG) is controlled by diffusible
      molecules that modulate neurogenic processes, including cell proliferation,
      differentiation and survival. To elucidate the mechanisms underlying hippocampal
      neurogenesis, we investigated the function of draxin, originally identified as a
      neural chemorepellent, in the regulation of neuronal survival in the DG. Draxin
      was expressed in Tbr2 (+) late progenitors and NeuroD1 (+) neuroblasts in the
      dentate granule cell lineage, whereas expression of its receptor DCC (deleted in
      colorectal cancer) was mainly detectable in neuroblasts. Our phenotypic analysis
      revealed that draxin deficiency led to enhanced apoptosis of DCC-expressing
      neuroblasts in the neurogenic areas. Furthermore, in vitro assays using a
      hippocampal neural stem/progenitor cell (HNSPC) line indicated that draxin
      inhibited apoptosis in differentiating HNSPCs, which express DCC. Taken together,
      we postulate that draxin plays a pivotal role in postnatal DG neurogenesis as a
      dependence receptor ligand for DCC to maintain and promote survival of
      neuroblasts.

PMID- 29339782
TI  - Loss of disease tolerance during Citrobacter rodentium infection is associated
      with impaired epithelial differentiation and hyperactivation of T cell responses.
AB  - Citrobacter rodentium is an intestinal mouse pathogen widely used as a model to
      study the mucosal response to infection. Inbred mouse strains suffer one of two
      fates following infection: self-limiting colitis or fatal diarrheal disease. We
      previously reported that Rspo2 is a major genetic determinant of the outcome of
      C. rodentium infection; Rspo2 induction during infection of susceptible mice
      leads to loss of intestinal function and mortality. Rspo2 induction does not
      impact bacterial colonization, but rather, impedes the ability of the host to
      tolerate C. rodentium infection. Here, we performed deep RNA sequencing and
      systematically analyzed the global gene expression profiles of C. rodentium
      infected colon tissues from susceptible and resistant congenic mice strains to
      determine the common responses to infection and the Rspo2-mediated dysfunction
      pathway signatures associated with loss of disease tolerance. Our results
      highlight changes in metabolism, tissue remodeling, and host defence as common
      responses to infection. Conversely, increased Wnt and stem cell signatures, loss
      of epithelial differentiation, and exaggerated CD4+ T cell activation through
      increased antigen processing and presentation were specifically associated with
      the response to infection in susceptible mice. These data provide insights into
      the molecular mechanisms underlying intestinal dysfunction and disease tolerance
      during C. rodentium infection.

PMID- 29339783
TI  - Global and regional importance of the direct dust-climate feedback.
AB  - Feedbacks between the global dust cycle and the climate system might have
      amplified past climate changes. Yet, it remains unclear what role the dust
      climate feedback will play in future anthropogenic climate change. Here, we
      estimate the direct dust-climate feedback, arising from changes in the dust
      direct radiative effect (DRE), using a simple theoretical framework that combines
      constraints on the dust DRE with a series of climate model results. We find that
      the direct dust-climate feedback is likely in the range of -0.04 to +0.02 Wm -2 K
      1, such that it could account for a substantial fraction of the total aerosol
      feedbacks in the climate system. On a regional scale, the direct dust-climate
      feedback is enhanced by approximately an order of magnitude close to major source
      regions. This suggests that it could play an important role in shaping the future
      climates of Northern Africa, the Sahel, the Mediterranean region, the Middle
      East, and Central Asia.

PMID- 29339784
TI  - Anisotropic sensor and memory device with a ferromagnetic tunnel barrier as the
      only magnetic element.
AB  - Multiple spin functionalities are probed on Pt/La2Co0.8Mn1.2O6/Nb:SrTiO3, a
      device composed by a ferromagnetic insulating barrier sandwiched between non
      magnetic electrodes. Uniquely, La2Co0.8Mn1.2O6 thin films present strong
      perpendicular magnetic anisotropy of magnetocrystalline origin, property of major
      interest for spintronics. The junction has an estimated spin-filtering efficiency
      of 99.7% and tunneling anisotropic magnetoresistance (TAMR) values up to 30% at
      low temperatures. This remarkable angular dependence of the magnetoresistance is
      associated with the magnetic anisotropy whose origin lies in the large spin-orbit
      interaction of Co2+ which is additionally tuned by the strain of the crystal
      lattice. Furthermore, we found that the junction can operate as an electrically
      readable magnetic memory device. The findings of this work demonstrate that a
      single ferromagnetic insulating barrier with strong magnetocrystalline anisotropy
      is sufficient for realizing sensor and memory functionalities in a tunneling
      device based on TAMR.

PMID- 29339785
TI  - The lncRNA GATA6-AS epigenetically regulates endothelial gene expression via
      interaction with LOXL2.
AB  - Impaired or excessive growth of endothelial cells contributes to several
      diseases. However, the functional involvement of regulatory long non-coding RNAs
      in these processes is not well defined. Here, we show that the long non-coding
      antisense transcript of GATA6 (GATA6-AS) interacts with the epigenetic regulator
      LOXL2 to regulate endothelial gene expression via changes in histone methylation.
      Using RNA deep sequencing, we find that GATA6-AS is upregulated in endothelial
      cells during hypoxia. Silencing of GATA6-AS diminishes TGF-beta2-induced
      endothelial-mesenchymal transition in vitro and promotes formation of blood
      vessels in mice. We identify LOXL2, known to remove activating H3K4me3 chromatin
      marks, as a GATA6-AS-associated protein, and reveal a set of angiogenesis-related
      genes that are inversely regulated by LOXL2 and GATA6-AS silencing. As GATA6-AS
      silencing reduces H3K4me3 methylation of two of these genes, periostin and
      cyclooxygenase-2, we conclude that GATA6-AS acts as negative regulator of nuclear
      LOXL2 function.

PMID- 29339786
TI  - Integrated miRNA-mRNA spatial signature for oral squamous cell carcinoma: a
      prospective profiling study of Narrow Band Imaging guided resection.
AB  - Oral squamous cell carcinoma (OSCC) is a common malignancy for which there is
      poor prognosis and limited therapeutic options. The objective was to identify
      mRNA targets of dysregulated miRNAs in OSCC using integrated analysis and
      understand molecular abnormality in surgical margins. We used biopsies along the
      spatial axis from normal tissue defined by narrow band imaging (NBI) through
      conventional white light (WL) margins to tumour from 18 patients undergoing
      surgical resection for OSCC. Overall 119 miRNA and 4794 mRNA were differentially
      expressed along the adjacent normal tissue to tumour axis. Analysis of miRNA
      profiles demonstrated the NBI margins were molecularly distinct from both the
      tumour and WL margin. Integrated analysis identified 193 miRNA-mRNA interactions
      correlated to the spatial axis of NBI-WL-T. We used cross-validation analysis to
      derive a spatial interactome signature of OSCC comprising 100 putative miRNA-mRNA
      interactions between 40 miRNA and 96 mRNA. Bioinformatic analysis suggests that
      miRNA dysregulation in OSCC may contribute to activation of the oncostatin M,
      BDNF and TGF-beta pathways. Our data demonstrates that surgical margins defined
      by NBI leave less potentially malignant residual tissue. The miRNA-mRNA
      interactome provides insight into dysregulated miRNA signalling in OSCC and
      supports molecular definition of tumour margins.

PMID- 29339787
TI  - Cilia-related protein SPEF2 regulates osteoblast differentiation.
AB  - Sperm flagellar protein 2 (SPEF2) is essential for motile cilia, and lack of
      SPEF2 function causes male infertility and primary ciliary dyskinesia. Cilia are
      pointing out from the cell surface and are involved in signal transduction from
      extracellular matrix, fluid flow and motility. It has been shown that cilia and
      cilia-related genes play essential role in commitment and differentiation of
      chondrocytes and osteoblasts during bone formation. Here we show that SPEF2 is
      expressed in bone and cartilage. The analysis of a Spef2 knockout (KO) mouse
      model revealed hydrocephalus, growth retardation and death prior to five weeks of
      age. To further elucidate the causes of growth retardation we analyzed the bone
      structure and possible effects of SPEF2 depletion on bone formation. In Spef2 KO
      mice, long bones (tibia and femur) were shorter compared to wild type, and X-ray
      analysis revealed reduced bone mineral content. Furthermore, we showed that the
      in vitro differentiation of osteoblasts isolated from Spef2 KO animals was
      compromised. In conclusion, this study reveals a novel function for SPEF2 in bone
      formation through regulation of osteoblast differentiation and bone growth.

PMID- 29339788
TI  - Band gap maps beyond the delocalization limit: correlation between optical band
      gaps and plasmon energies at the nanoscale.
AB  - Recent progresses in nanoscale semiconductor technology have heightened the need
      for measurements of band gaps with high spatial resolution. Band gap mapping can
      be performed through a combination of probe-corrected scanning transmission
      electron microscopy (STEM) and monochromated electron energy-loss spectroscopy
      (EELS), but are rare owing to the complexity of the experiments and the data
      analysis. Furthermore, although this method is far superior in terms of spatial
      resolution to any other techniques, it is still fundamentally resolution-limited
      due to inelastic delocalization of the EELS signal. In this work we have
      established a quantitative correlation between optical band gaps and plasmon
      energies using the Zn1-xCd x O/ZnO system as an example, thereby side-stepping
      the fundamental resolution limits of band gap measurements, and providing a
      simple and convenient approach to achieve band gap maps with unprecedented
      spatial resolution.

PMID- 29339790
TI  - Decoding the dynamic representation of musical pitch from human brain activity.
AB  - In music, the perception of pitch is governed largely by its tonal function given
      the preceding harmonic structure of the music. While behavioral research has
      advanced our understanding of the perceptual representation of musical pitch,
      relatively little is known about its representational structure in the brain.
      Using Magnetoencephalography (MEG), we recorded evoked neural responses to
      different tones presented within a tonal context. Multivariate Pattern Analysis
      (MVPA) was applied to "decode" the stimulus that listeners heard based on the
      underlying neural activity. We then characterized the structure of the brain's
      representation using decoding accuracy as a proxy for representational distance,
      and compared this structure to several well established perceptual and acoustic
      models. The observed neural representation was best accounted for by a model
      based on the Standard Tonal Hierarchy, whereby differences in the neural encoding
      of musical pitches correspond to their differences in perceived stability. By
      confirming that perceptual differences honor those in the underlying neuronal
      population coding, our results provide a crucial link in understanding the
      cognitive foundations of musical pitch across psychological and neural domains.

PMID- 29339789
TI  - Exosome-mediated breast cancer chemoresistance via miR-155 transfer.
AB  - Breast cancer remains the most prevalent cause of cancer mortality in woman
      worldwide due to the metastatic process and therapy resistance. Resistance
      against cancer therapy is partially attributed to cancer stem cells (CSCs). These
      cells arise from epithelial cells undergoing epithelial-to-mesenchymal transition
      (EMT) and might be responsible for tumor recurrence. In this study, we reported
      the relevance of miR-155 upregulation in chemoresistant cells associated with
      EMT. Notably, we found miR-155 induction in exosomes isolated from CSCs and
      resistant cells, followed by resistant cells' exosome transfer to the recipient
      sensitive cells. Functionally, miR-155 mimic assay showed an enrichment in miR
      155 from exosome concomitant with miR-155 exosome transfer to breast cancer
      cells. In parallel to these effects, we also observed EMT change in miR-155
      transfected cells. The chemoresistance phenotype transfer to sensitive cells and
      the migration capability was analyzed by MTT and scratch assays and our results
      suggest that exosomes may intermediate resistance and migration capacity to
      sensitive cells partly through exosome transfer of miR-155. Taken together, our
      findings establish the significance of exosome-mediate miR-155 chemoresistance in
      breast cancer cells, with implications for targeting miR-155 signaling as a
      possible therapeutic strategy.

PMID- 29339792
TI  - Assemble-And-Match: A Novel Hybrid Tool for Enhancing Education and Research in
      Rational Structure Based Drug Design.
AB  - Rational drug design is the process of finding new medication that can activate
      or inhibit the biofunction of a target molecule by binding to it and forming a
      molecular complex. Here, shape and charge complementarities between drug and
      target are key. To help find effective drug molecules out of a huge pool of
      possibilities, physical and computer aided tools have been developed. Former
      offers a tangible experience of the molecular interactions yet lacks measurement
      and evaluation capabilities. Latter enables accurate and fast evaluations, but
      does not deliver the interactive tangible experience of physical models. We
      introduce a novel hybrid model called "Assemble-And-Match" where, we enhance and
      combine the unique features of the two categories. Assemble-And-Match works based
      on fabrication of customized molecular fragments using our developed software and
      a 3D printer. Fragments are hinged to each other in different combinations and
      form flexible peptide chains, conformable to tertiary structures, to fit in the
      binding pocket of a (3D printed) target molecule. Through embedded measurement
      marks, the molecular model is reconstructed in silico and its properties are
      evaluated. We expect Assemble-And-Match tool can enable combination of
      visuospatial perception with in silico computational power to aid research and
      education in drug design.

PMID- 29339791
TI  - The GluN2A Subunit Regulates Neuronal NMDA receptor-Induced Microglia-Neuron
      Physical Interactions.
AB  - Microglia are known to engage in physical interactions with neurons. However, our
      understanding of the detailed mechanistic regulation of microglia-neuron
      interactions is incomplete. Here, using high resolution two photon imaging, we
      investigated the regulation of NMDA receptor-induced microglia-neuron physical
      interactions. We found that the GluN2A inhibitor NVPAAM007, but not the GluN2B
      inhibitor ifenprodil, blocked the occurrence of these interactions. Consistent
      with the well-known developmental regulation of the GluN2A subunit, these
      interactions are absent in neonatal tissues. Furthermore, consistent with a
      preferential synaptic localization of GluN2A subunits, there is a differential
      sensitivity of their occurrence between denser (stratum radiatum) and less dense
      (stratum pyramidale) synaptic sub-regions of the CA1. Finally, consistent with
      differentially expressed GluN2A subunits in the CA1 and DG areas of the
      hippocampus, these interactions could not be elicited in the DG despite robust
      microglial chemotactic capabilities. Together, these results enhance our
      understanding of the mechanistic regulation of NMDA receptor-dependent microglia
      neuronal physical interactions phenomena by the GluN2A subunit that may be
      relevant in the mammalian brain during heightened glutamatergic neurotransmission
      such as epilepsy and ischemic stroke.

PMID- 29339793
TI  - Skin-inspired highly stretchable and conformable matrix networks for
      multifunctional sensing.
AB  - Mechanosensation electronics (or Electronic skin, e-skin) consists of
      mechanically flexible and stretchable sensor networks that can detect and
      quantify various stimuli to mimic the human somatosensory system, with the
      sensations of touch, heat/cold, and pain in skin through various sensory
      receptors and neural pathways. Here we present a skin-inspired highly stretchable
      and conformable matrix network (SCMN) that successfully expands the e-skin
      sensing functionality including but not limited to temperature, in-plane strain,
      humidity, light, magnetic field, pressure, and proximity. The actualized specific
      expandable sensor units integrated on a structured polyimide network, potentially
      in three-dimensional (3D) integration scheme, can also fulfill simultaneous multi
      stimulus sensing and achieve an adjustable sensing range and large-area
      expandability. We further construct a personalized intelligent prosthesis and
      demonstrate its use in real-time spatial pressure mapping and temperature
      estimation. Looking forward, this SCMN has broader applications in humanoid
      robotics, new prosthetics, human-machine interfaces, and health-monitoring
      technologies.

PMID- 29339794
TI  - HPV-16 virions can remain infectious for 2 weeks on senescent cells but require
      cell cycle re-activation to allow virus entry.
AB  - Successful infection with Human Papillomaviruses requires mitosis, when incoming
      viral genomes gain access to nuclear components. However, very little is known
      about how long HPV particles can remain infectious in non-dividing cells or in
      which cellular compartments these viruses may reside. To investigate these
      questions we have used BJ cells as a reversible model of senescence and show that
      HPV-16 can only infect early-passage proliferating cells. Late-passage senescent
      cells are resistant to HPV infection, but this can be reversed by inducing cell
      cycle re-entry with a p53 siRNA. In senescent cells we find that efficient virus
      entry can be attained upon cell cycle re-entry 16 days after infection,
      demonstrating that HPV can persist for 2 weeks prior to induction of mitosis.
      However, exposing cells to anti-HPV-16 L1 neutralising antibody blocks infection
      at these late time points, suggesting that the virions reside near the cell
      surface. Indeed, immunofluorescence analysis shows that virions accumulate on the
      cell surface of senescent cells and only enter endocytic vesicles upon
      stimulation with p53 siRNA. These results demonstrate that HPV-16 virions can
      remain viable on a non-dividing cell for extended periods of time, but are
      nonetheless vulnerable to antibody-induced neutralisation throughout.

PMID- 29339795
TI  - Lipidized prolactin-releasing peptide improved glucose tolerance in metabolic
      syndrome: Koletsky and spontaneously hypertensive rat study.
AB  - BACKGROUND/OBJECTIVES: Prolactin-releasing peptide (PrRP) has a potential to
      decrease food intake and ameliorate obesity, but is ineffective after peripheral
      administration. We have previously shown that our novel lipidized analogs PrRP
      enhances its stability in the circulation and enables its central effect after
      peripheral application. The purpose of this study was to explore if sub-chronic
      administration of novel PrRP analog palmitoylated in position 11 (palm11-PrRP31)
      to Koletsky-spontaneously hypertensive obese rats (SHROB) could lower body weight
      and glucose intolerance as well as other metabolic parameters. SUBJECTS/METHODS:
      The SHROB rats (n = 16) were used for this study and age-matched hypertensive
      lean SHR littermates (n = 16) served as controls. Palm11-PrRP31 was administered
      intraperitoneally to SHR and SHROB (n = 8) at a dose of 5 mg/kg once-daily for 3
      weeks. During the dosing period food intake and body weight were monitored. At
      the end of the experiment the oral glucose tolerance test was performed; plasma
      and tissue samples were collected. Thereafter, arterial blood pressure was
      measured. RESULTS: At the end of the experiment, vehicle-treated SHROB rats
      showed typical metabolic syndrome parameters, including obesity, glucose
      intolerance, dyslipidemia, and hypertension. Peripheral treatment with palm11
      PrRP31 progressively decreased the body weight of SHR rats but not SHROB rats,
      though glucose tolerance was markedly improved in both strains. Moreover, in
      SHROB palm11-PrRP31 ameliorated the HOMA index, insulin/glucagon ratio, and
      increased insulin receptor substrate 1 and 2 expression in fat and insulin
      signaling in the hypothalamus, while it had no effect on blood pressure.
      CONCLUSIONS: We demonstrated that our new lipidized PrRP analog is capable of
      improving glucose tolerance in obese SHROB rats after peripheral application,
      suggesting that its effect on glucose metabolism is independent of leptin
      signaling and body weight lowering. These data suggest that this analog has the
      potential to be a compound with both anti-obesity and glucose-lowering
      properties.

PMID- 29339796
TI  - A user's guide to the ambiguous word 'epigenetics'.

PMID- 29339799
TI  - Complementary therapies for fatigue after hematopoietic stem cell
      transplantation: an integrative review.
AB  - Fatigue after hematopoietic stem cell transplantation (HSCT) is a persistent
      problem that limits activities and causes distress. Complementary therapies have
      shown promising results in improving fatigue in several patient populations.
      However, it is unknown whether they have the same effect on fatigue in the HSCT
      population. This integrative review aimed to explore the literature that
      evaluated complementary therapies for fatigue among HSCT patients. Only eight
      studies were considered eligible for inclusion in this review. The eight studies
      evaluated music therapy, relaxation, mindfulness, and massage techniques with
      mixed results. These studies had major methodological limitations, such as the
      small sample sizes and not blinding participants to the treatment allocation,
      introducing possible bias. Furthermore, most of these studies used 'usual care'
      control groups, leaving it unclear to what extent the observed effects are based
      on the effects of complementary therapies, or rather on psychosocial factors such
      as personal attention. More research is needed to more rigorously evaluate these
      and other complementary therapies for the prevalent problem of fatigue in the
      HSCT population.

PMID- 29339797
TI  - A brave new world of RNA-binding proteins.
AB  - RNA-binding proteins (RBPs) are typically thought of as proteins that bind RNA
      through one or multiple globular RNA-binding domains (RBDs) and change the fate
      or function of the bound RNAs. Several hundred such RBPs have been discovered and
      investigated over the years. Recent proteome-wide studies have more than doubled
      the number of proteins implicated in RNA binding and uncovered hundreds of
      additional RBPs lacking conventional RBDs. In this Review, we discuss these new
      RBPs and the emerging understanding of their unexpected modes of RNA binding,
      which can be mediated by intrinsically disordered regions, protein-protein
      interaction interfaces and enzymatic cores, among others. We also discuss the RNA
      targets and molecular and cellular functions of the new RBPs, as well as the
      possibility that some RBPs may be regulated by RNA rather than regulate RNA.

PMID- 29339800
TI  - Haploidentical hematopoietic stem cell transplant for patients with sickle cell
      disease using thiotepa, fludarabine, thymoglobulin, low dose cyclophosphamide,
      200 cGy tbi and post transplant cyclophosphamide.

PMID- 29339798
TI  - Shedding light on the cell biology of extracellular vesicles.
AB  - Extracellular vesicles are a heterogeneous group of cell-derived membranous
      structures comprising exosomes and microvesicles, which originate from the
      endosomal system or which are shed from the plasma membrane, respectively. They
      are present in biological fluids and are involved in multiple physiological and
      pathological processes. Extracellular vesicles are now considered as an
      additional mechanism for intercellular communication, allowing cells to exchange
      proteins, lipids and genetic material. Knowledge of the cellular processes that
      govern extracellular vesicle biology is essential to shed light on the
      physiological and pathological functions of these vesicles as well as on clinical
      applications involving their use and/or analysis. However, in this expanding
      field, much remains unknown regarding the origin, biogenesis, secretion,
      targeting and fate of these vesicles.

PMID- 29339802
TI  - Biases of STRUCTURE software when exploring introduction routes of invasive
      species.
AB  - Population genetic methods are widely used to retrace the introduction routes of
      invasive species. The unsupervised Bayesian clustering algorithm implemented in
      STRUCTURE is amongst the most frequently used of these methods, but its ability
      to provide reliable information about introduction routes has never been
      assessed. We simulated microsatellite datasets to evaluate the extent to which
      the results provided by STRUCTURE were misleading for the inference of
      introduction routes. We focused on an invasion scenario involving one native and
      two independently introduced populations, because it is the sole scenario that
      can be rejected when obtaining a particular clustering with a STRUCTURE analysis
      at K = 2 (two clusters). Results were classified as "misleading" or "non
      misleading". We investigated the influence of effective size, bottleneck severity
      and number of loci on the type and frequency of misleading results. We showed
      that misleading STRUCTURE results were obtained for 10% of all simulated
      datasets. Our results highlighted two categories of misleading output. The first
      occurs when the native population has a low level of diversity. In this case, the
      two introduced populations may be very similar, despite their independent
      introduction histories. The second category results from convergence issues in
      STRUCTURE for K = 2, with strong bottleneck severity and/or large numbers of loci
      resulting in high levels of differentiation between the three populations.
      Overall, the risk of being misled by STRUCTURE in the context of introduction
      routes inferences is moderate, but it is important to remain cautious when low
      genetic diversity or genuine multimodality between runs are involved.

PMID- 29339801
TI  - Cardiac glycoside/aglycones inhibit HIV-1 gene expression by a mechanism
      requiring MEK1/2-ERK1/2 signaling.
AB  - The capacity of HIV-1 to develop resistance to current drugs calls for innovative
      strategies to control this infection. We aimed at developing novel inhibitors of
      HIV-1 replication by targeting viral RNA processing-a stage dependent on
      conserved host processes. We previously reported that digoxin is a potent
      inhibitor of this stage. Herein, we identify 12 other cardiac glycoside/aglycones
      or cardiotonic steroids (CSs) that impede HIV growth in HIV-infected T cells from
      clinical patients at IC50s (1.1-1.3 nM) that are 2-26 times below concentrations
      used in patients with heart conditions. We subsequently demonstrate that CSs
      inhibit HIV-1 gene expression in part through modulation of MEK1/2-ERK1/2
      signaling via interaction with the Na+/K+-ATPase, independent of alterations in
      intracellular Ca2+. Supporting this hypothesis, depletion of the Na+/K+-ATPase or
      addition of a MEK1/2-ERK1/2 activator also impairs HIV-1 gene expression. Similar
      to digoxin, all CSs tested induce oversplicing of HIV-1 RNAs, reducing unspliced
      (Gag) and singly spliced RNAs (Env/p14-Tat) encoding essential HIV-1
      structural/regulatory proteins. Furthermore, all CSs cause nuclear retention of
      genomic/unspliced RNAs, supporting viral RNA processing as the underlying
      mechanism for their disruption of HIV-1 replication. These findings call for
      further in vivo validation and supports the targeting of cellular processes to
      control HIV-1 infection.

PMID- 29339803
TI  - Carbohydrates protect protein against abiotic fragmentation by soil minerals.
AB  - The degradation and turnover of soil organic matter is an important part of
      global carbon cycling and of particular importance with respect to attempts to
      predict the response of ecosystems to global climate change. Thus, it is
      important to mechanistically understand the processes by which organic matter can
      be degraded in the soil environment, including contact with reactive or catalytic
      mineral surfaces. We have characterized the outcome of the interaction of two
      minerals, birnessite and kaolinite, with two disaccharides, cellobiose and
      trehalose. These results show that birnessite reacts with and degrades the
      carbohydrates, while kaolinite does not. The reaction of disaccharides with
      birnessite produces Mn(II), indicating that degradation of the disaccharides is
      the result of their oxidation by birnessite. Furthermore, we find that both
      sugars can inhibit the degradation of a model protein by birnessite,
      demonstrating that the presence of one organic constituent can impact abiotic
      degradation of another. Therefore, both the reactivity of the mineral matrix and
      the presence of certain organic constituents influence the outcomes of abiotic
      degradation. These results suggest the possibility that microorganisms may be
      able to control the functionality of exoenzymes through the concomitant excretion
      of protective organic substances, such as those found in biofilms.

PMID- 29339805
TI  - First description of behavior and immune system relationship in fish.
AB  - Considering the intriguing relationship between immune system and behavior
      recently described in mammals, and the lack of information of this relationship
      in fish, here we describe for the first time the interaction between the immune
      system and social and exploratory behavior in zebrafish. Fish high responders to
      novelty (HRN) presented a proinflammatory profile, with increased IL-1beta and
      reduced IL-10 expression compared to fish low responders to novelty (LRN).
      Likewise, fish less responsive to social stimuli have a reduced expression of INF
      gamma. We show that fish with different behavior patterns have differences in the
      immune response. Our findings indicate that the interplay between immune system
      and behavior in zebrafish is similar to that found in mammalian models and that
      zebrafish should be considered as a potential model organism to study the
      relationship between immune system and behavior.

PMID- 29339804
TI  - EPHB6 and testosterone in concert regulate epinephrine release by adrenal gland
      chromaffin cells.
AB  - Erythropoietin-producing human hepatocellular receptor (EPH) B6 (EPHB6) is a
      member of the receptor tyrosine kinase family. We previously demonstrated that
      EPHB6 knockout reduces catecholamine secretion in male but not female mice, and
      castration reverses this phenotype. We showed here that male EPHB6 knockout
      adrenal gland chromaffin cells presented reduced acetylcholine-triggered Ca2+
      influx. Such reduction depended on the non-genomic effect of testosterone.
      Increased large conductance calcium-activated potassium channel current densities
      were recorded in adrenal gland chromaffin cells from male EPHB6 knockout mice but
      not from castrated knockout or female knockout mice. Blocking of the large
      conductance calcium-activated potassium channel in adrenal gland chromaffin cells
      from male knockout mice corrected their reduced Ca2+ influx. We conclude that the
      absence of EPHB6 and the presence of testosterone would lead to augmented large
      conductance calcium-activated potassium channel currents, which limit voltage
      gated calcium channel opening in adrenal gland chromaffin cells. Consequently,
      acetylcholine-triggered Ca2+ influx is reduced, leading to lower catecholamine
      release in adrenal gland chromaffin cells from male knockout mice. This explains
      the reduced resting-state blood catecholamine levels, and hence the blood
      pressure, in male but not female EPHB6 knock mice. These findings have certain
      clinical implications.

PMID- 29339806
TI  - Tumor characteristics, treatments, and oncological outcomes of prostate cancer in
      men aged <=50 years: a population-based study.
AB  - BACKGROUND: To examine clinical characteristics, treatment modalities and
      oncological outcomes of prostate cancer (PCa) according to young (<=50) vs. old
      age. METHODS: Of 407,599 men with primary adenocarcinoma of the prostate within
      the Surveillance, Epidemiology and End Results (SEER)-database (2004 to 2013),
      18,387 were aged <=50 years (4.5%). Time trends, cumulative incidence, and
      competing risks regression (CRR) analyses tested for differences between young
      and old patients. Multi-variable analyses were adjusted for year of diagnosis,
      race, marital status, Gleason Score, clinical tumor stage, and lymph node status.
      RESULTS: Younger men had more favorable tumor characteristics: lower Gleason
      Score, lower median PSA, and lower rates of metastases at diagnosis compared to
      their older counterparts. Over time, no local treatment (NLT) rates increased,
      radical prostatectomy (RP), and brachytherapy (BT) rates decreased and external
      beam radiation (EBRT) rates remained unchanged. Moreover, the rate of de novo
      metastatic prostate cancer increased in young patients from 2% (2004) to 3.2%
      (2013) (p = 0.004). CRR models showed no difference in prostate cancer-specific
      mortality (PCSM) between young and old, across all local treatment types.
      CONCLUSIONS: Young PCa patients have more favorable disease characteristics at
      presentation, are less frequently treated with RP or BT and more frequently
      benefit of NLT. PCSM did not differ between young and old patients. However, it
      is worrisome that recently more young PCa patients are diagnosed at a metastatic
      stage.

PMID- 29339808
TI  - Gut microbiota: Filling up on fibre for a healthy gut.

PMID- 29339807
TI  - Overexpression of alpha (1,6) fucosyltransferase in the development of castration
      resistant prostate cancer cells.
AB  - Glycosylation is recognized as one of the most common modifications on proteins.
      Recent studies have shown that aberrant expression of alpha (1,6)
      fucosyltransferase (FUT8), which catalyzes the transfer of fucose from GDP-fucose
      to core-GlcNAc of the N-linked glycoproteins, modulates cellular behavior that
      could lead to the development of aggressive prostate cancer. While the
      relationship between the abnormal expression of FUT8 and glycoprotein
      fucosylation in different prostate cancer cells has been demonstrated, there is
      no evidence that shows dysregulated fucosylation might be involved in prostate
      cancer progression from androgen-dependent to castration-resistant prostate
      cancer. In this study, using a proteomics approach, we analyzed androgen
      dependent and androgen-resistant LAPC4 cells and identified FUT8 to be
      significantly overexpressed in the androgen-resistant LAPC4 cells. These findings
      were independently confirmed in LAPC4 cells that were treated with non-steroidal
      anti-androgen (bicalutamide) and in the in vivo castrated tumor xenograft models.
      Similarly, we also demonstrated that overexpression of FUT8 might be responsible
      for the decreased PSA expression in prostate cancer specimens. To our knowledge,
      this is the first study reporting the functional role of fucosylated enzyme in
      the development of castration-resistant prostate cancer.

PMID- 29339809
TI  - Gut microbiota: Targeting of specific microbial species mitigates colitis.

PMID- 29339811
TI  - Diagnosis: Gas-sensing gut capsules.

PMID- 29339810
TI  - Extrahepatic cancers and chronic HCV infection.
AB  - Infectious agents, such as HCV, account for ~15% of human cancers. HCV infects
      not only hepatocytes but also extrahepatic cells. Chronic HCV infection can
      induce chronic inflammation with qualitative and quantitative alterations of the
      immune repertoire and tissue microenvironment, which could induce various
      neoplasias. Epidemiological studies and meta-analyses suggest an increased rate
      of extrahepatic cancers in patients with chronic HCV infection along with a
      higher risk of intrahepatic cholangiocarcinoma, pancreatic cancer and non-Hodgkin
      lymphoma (NHL), highlighting the need to screen for HCV infection in patients
      with these cancers. Development of B cell NHL has been associated with HCV
      infection, with a relative risk of ~1.5. Direct transformation related to the
      presence of the virus and chronic antigenic stimulation are the two major non
      exclusive mechanisms involved in HCV-related lymphomagenesis. HCV infection
      alters survival of patients with lymphoma, and sustained virologic response (SVR)
      substantially improves prognosis. Antiviral treatments might induce remission of
      indolent lymphoma when SVR is achieved even without chemotherapy, emphasizing the
      role of HCV in lymphomagenesis in this context. However, studies are needed to
      provide prospective evidence of a causal relationship between chronic HCV
      infection and other extrahepatic cancers and to determine whether the risk of
      extrahepatic cancers is reduced with SVR. In this Review, we report on recent
      studies analysing the risk of extrahepatic cancers associated with chronic HCV
      infection. Although there is no doubt regarding the direct and indirect causality
      between HCV and NHL, an increased risk of other cancers is less clear, with the
      exception of cholangiocarcinoma.

PMID- 29339812
TI  - Colorectal cancer: Hand-in-hand - colorectal cancer metastasizes with
      microorganisms.

PMID- 29339813
TI  - A new group of synthetic phenolic-containing amphiphilic molecules for
      multipurpose applications: Physico-chemical characterization and cell-toxicity
      study.
AB  - Nine synthetic amphiphilic phenolic lipids, varied in phenolic moiety
      (caffeoyl/dimethylcaffeoyl) and fatty acid chain lengths (8-18) were
      characterized by differential scanning calorimetry (DSC), temperature-ramp
      Fourier transform infra-red spectroscopy (FT-IR) and atomic force microscopy
      (AFM). FT-IR and DSC results revealed that the physical state and lateral packing
      of synthetic molecules were largely governed by fatty acyls. The critical micelle
      concentrations (CMC) of synthetic lipids was in the range of 0.1 mM to 2.5 mM,
      affording generation of stable oil-in-water emulsions; as evidenced by the
      creaming index (<5%) of emulsions stabilized by compounds C12-C16, and C12a-C16a
      after 7 days' storage. AFM analysis revealed that compound C14 formed stable
      double-layers films of 5.2 nm and 6.7 nm. Application studies showed that
      formulations stabilized by synthesized compounds containing 30% fish oil had
      superior physical and oxidative stability compared to formulations containing
      commercial emulsifiers or their mixtures with phenolic acids. Moreover, the
      synthetic compounds were non-toxic against in vitro transformed keratinocytes
      from histologically normal skin and Caco-2 cell lines. This study demonstrates
      the relevance of using a natural hydroxycarboxylic acid as a flexible linker
      between natural antioxidants, glycerol and fatty acids to generate
      multifunctional amphiphiles with potential applications in food, pharmaceutical
      and cosmetic industry.

PMID- 29339814
TI  - Long-lived hot-carrier light emission and large blue shift in formamidinium tin
      triiodide perovskites.
AB  - A long-lived hot carrier population is critical in order to develop working hot
      carrier photovoltaic devices with efficiencies exceeding the Shockley-Queisser
      limit. Here, we report photoluminescence from hot-carriers with unexpectedly long
      lifetime (a few ns) in formamidinium tin triiodide. An unusual large blue shift
      of the time-integrated photoluminescence with increasing excitation power (150
      meV at 24 K and 75 meV at 293 K) is displayed. On the basis of the analysis of
      energy-resolved and time-resolved photoluminescence, we posit that these
      phenomena are associated with slow hot carrier relaxation and state-filling of
      band edge states. These observations are both important for our understanding of
      lead-free hybrid perovskites and for an eventual future development of efficient
      lead-free perovskite photovoltaics.

PMID- 29339815
TI  - MCL-1 is a prognostic indicator and drug target in breast cancer.
AB  - Analysis of publicly available genomic and gene expression data demonstrates that
      MCL1 expression is frequently elevated in breast cancer. Distinct from other pro
      survival Bcl-2 family members, the short half-life of MCL-1 protein led us to
      investigate MCL-1 protein expression in a breast cancer tissue microarray and
      correlate this with clinical data. Here, we report associations between high MCL
      1 and poor prognosis in specific subtypes of breast cancer including triple
      negative breast cancer, an aggressive form that lacks targeted treatment options.
      Deletion of MCL-1 in the mammary epithelium of genetically engineered mice
      revealed an absolute requirement for MCL-1 in breast tumorigenesis. The clinical
      applicability of these findings was tested through a combination of approaches
      including knock-down or inhibition of MCL-1 to show triple-negative breast cancer
      cell line dependence on MCL-1 in vitro and in vivo. Our data demonstrate that
      high MCL-1 protein expression is associated with poor outcome in breast cancer
      and support the therapeutic targeting of MCL-1 in this disease.

PMID- 29339816
TI  - Dinuclear PhosphoiminoBINOL-Pd Container for Malononitrile: Catalytic Asymmetric
      Double Mannich Reaction for Chiral 1,3-Diamine Synthesis.
AB  - A phosphoiminoBINOL ligand was designed to form a dinuclear metal complex that
      could hold a malononitrile molecule. The dinuclear bis(phosphoimino)binaphthoxy
      Pd2(OAc)2 complex catalyzed a double Mannich reaction of N-Boc-imines with
      malononitrile to give chiral 1,3-diamines with high enantioselectivity. The
      rational asymmetric catalyst, which smoothly introduces the first coupling
      product to the second coupling reaction while avoiding the reverse reaction,
      facilitates the over-reaction into a productive reaction process.

PMID- 29339817
TI  - Cooperating with machines.
AB  - Since Alan Turing envisioned artificial intelligence, technical progress has
      often been measured by the ability to defeat humans in zero-sum encounters (e.g.,
      Chess, Poker, or Go). Less attention has been given to scenarios in which human
      machine cooperation is beneficial but non-trivial, such as scenarios in which
      human and machine preferences are neither fully aligned nor fully in conflict.
      Cooperation does not require sheer computational power, but instead is
      facilitated by intuition, cultural norms, emotions, signals, and pre-evolved
      dispositions. Here, we develop an algorithm that combines a state-of-the-art
      reinforcement-learning algorithm with mechanisms for signaling. We show that this
      algorithm can cooperate with people and other algorithms at levels that rival
      human cooperation in a variety of two-player repeated stochastic games. These
      results indicate that general human-machine cooperation is achievable using a non
      trivial, but ultimately simple, set of algorithmic mechanisms.

PMID- 29339818
TI  - Development and optimization of a differentiated airway epithelial cell model of
      the bovine respiratory tract.
AB  - Cattle are subject to economically-important respiratory tract infections by
      various bacterial and viral pathogens and there is an urgent need for the
      development of more realistic in vitro models of the bovine respiratory tract to
      improve our knowledge of disease pathogenesis. In the present study, we have
      optimized the culture conditions in serum-free medium that allow bovine bronchial
      epithelial cells (BBECs) grown at an air-liquid interface to differentiate into a
      three-dimensional epithelium that is highly representative of the bovine airway.
      Epidermal growth factor was required to trigger both proliferation and
      differentiation of BBECs whilst retinoic acid was also essential for mucociliary
      differentiation. Triiodothyronine was demonstrated not to be important for the
      differentiation of BBECs. Oxygen concentration had a minimal effect although
      optimal ciliation was achieved when BBECs were cultured at 14% oxygen tension.
      Insert pore-density had a significant effect on the growth and differentiation of
      BBECs; a high-pore-density was required to trigger optimum differentiation. The
      established BBEC model will have wide-ranging applications for the study of
      bacterial and viral infections of the bovine respiratory tract; it will
      contribute to the development of improved vaccines and therapeutics and will
      reduce the use of cattle in in vivo experimentation.

PMID- 29339819
TI  - Ancient Human Migrations to and through Jammu Kashmir- India were not of Males
      Exclusively.
AB  - Jammu and Kashmir (J&K), the Northern most State of India, has been under
      represented or altogether absent in most of the phylogenetic studies carried out
      in literature, despite its strategic location in the Himalayan region.
      Nonetheless, this region may have acted as a corridor to various migrations to
      and from mainland India, Eurasia or northeast Asia. The belief goes that most of
      the migrations post-late-Pleistocene were mainly male dominated, primarily
      associated with population invasions, where female migration may thus have been
      limited. To evaluate female-centered migration patterns in the region, we
      sequenced 83 complete mitochondrial genomes of unrelated individuals belonging to
      different ethnic groups from the state. We observed a high diversity in the
      studied maternal lineages, identifying 19 new maternal sub-haplogroups (HGs).
      High maternal diversity and our phylogenetic analyses suggest that the migrations
      post-Pleistocene were not strictly paternal, as described in the literature.
      These preliminary observations highlight the need to carry out an extensive study
      of the endogamous populations of the region to unravel many facts and find links
      in the peopling of India.

PMID- 29339820
TI  - Histone Variant MacroH2A1 Plays an Isoform-Specific Role in Suppressing
      Epithelial-Mesenchymal Transition.
AB  - Epithelial-Mesenchymal Transition (EMT) is a biological program that plays key
      roles in various developmental and pathological processes. Although much work has
      been done on signaling pathways and transcription factors regulating EMT, the
      epigenetic regulation of EMT remains not well understood. Histone variants have
      been recognized as a key group of epigenetic regulators. Among them, macroH2A1 is
      involved in stem cell reprogramming and cancer progression. We postulated that
      macroH2A1 may play a role in EMT, a process involving reprogramming of cellular
      states. In this study, we demonstrate that expression of macroH2A1 is
      dramatically reduced during EMT induction in immortalized human mammary
      epithelial cells (HMLE). Moreover, ectopic expression of the macroH2A1.1 isoform,
      but not macroH2A1.2, can suppress EMT induction and reduce the stem-like cell
      population in HMLE. Interestingly, macroH2A1.1 overexpression cannot revert
      stable mesenchymal cells back to the epithelial state, suggesting a stage
      specific role of macroH2A1.1 in EMT. We further pinpointed that the function of
      macroH2A1.1 in EMT suppression is dependent on its ability to bind the NAD+
      metabolite PAR, in agreement with the inability to suppress EMT by macroH2A1.2,
      which lacks the PAR binding domain. Thus, our work discovered a previously
      unrecognized isoform-specific function of macroH2A1 in regulating EMT induction.

PMID- 29339823
TI  - Phosphate insensitive aminophosphonate mineralisation within oceanic nutrient
      cycles.
AB  - Many areas of the ocean are nutrient-poor yet support large microbial
      populations, leading to intense competition for and recycling of nutrients.
      Organic phosphonates are frequently found in marine waters, but require
      specialist enzymes for catabolism. Previous studies have shown that the genes
      that encode these enzymes in marine systems are under Pho regulon control and so
      are repressed by inorganic phosphate. This has led to the conclusion that
      phosphonates are recalcitrant in much of the ocean, where phosphorus is not
      limiting despite the degradative genes being common throughout the marine
      environment. Here we challenge this paradigm and show, for the first time, that
      bacteria isolated from marine samples have the ability to mineralise 2
      aminoethylphosphonate, the most common biogenic marine aminophosphonate, via
      substrate-inducible gene regulation rather than via Pho-regulated metabolism.
      Substrate-inducible, Pho-independent 2-aminoethylphosphonate catabolism therefore
      represents a previously unrecognised component of the oceanic carbon, nitrogen
      and phosphorus cycles.

PMID- 29339822
TI  - Relationship between brachial-ankle and heart-femoral pulse wave velocities and
      the rapid decline of kidney function.
AB  - The impact of brachial-ankle pulse wave velocity (baPWV) and heart-femoral pulse
      wave velocity (hfPWV) on rapid decline of estimated glomerular filtration rate
      (eGFR) has been inconclusive. The database of a multicenter prospective study of
      2238 patients in Korea enrolled from 2011 to 2016 was reviewed. After excluding
      patients with missing baPWV (n = 257) and eGFR change (n = 180), the study
      included 1801 non-dialysis chronic kidney disease (CKD) patients. The eGFR change
      <-5ml/min/1.73 m2/year was defined as rapid decline. During a mean of 2.2 years,
      the mean eGFR change was -3.6 ml/min/1.73 m2/year, and 31.6% of patients were
      classified as having rapid decline. Older age, causes of CKD, increased heart
      rate, systolic blood pressures, and proteinuria were associated with the highest
      baPWV quintile. In multivariate logistic regression analyses, the odds of a rapid
      decline in eGFR was 1.9 times higher in the fifth quintile than in the first
      quintile (P = 0.013). In a subset with baPWV and hfPWV (n = 1182), high baPWV was
      associated with rapid eGFR decline only when accompanied by a high hfPWV. These
      findings suggest that central and peripheral PWVs may simultaneously affect rapid
      eGFR decline.

PMID- 29339821
TI  - Cigarette smoking is associated with an altered vaginal tract metabolomic
      profile.
AB  - Cigarette smoking has been associated with both the diagnosis of bacterial
      vaginosis (BV) and a vaginal microbiota lacking protective Lactobacillus spp. As
      the mechanism linking smoking with vaginal microbiota and BV is unclear, we
      sought to compare the vaginal metabolomes of smokers and non-smokers (17
      smokers/19 non-smokers). Metabolomic profiles were determined by gas and liquid
      chromatography mass spectrometry in a cross-sectional study. Analysis of the 16S
      rRNA gene populations revealed samples clustered into three community state types
      (CSTs) ---- CST-I (L. crispatus-dominated), CST-III (L. iners-dominated) or CST
      IV (low-Lactobacillus). We identified 607 metabolites, including 12 that differed
      significantly (q-value < 0.05) between smokers and non-smokers. Nicotine, and the
      breakdown metabolites cotinine and hydroxycotinine were substantially higher in
      smokers, as expected. Among women categorized to CST-IV, biogenic amines,
      including agmatine, cadaverine, putrescine, tryptamine and tyramine were
      substantially higher in smokers, while dipeptides were lower in smokers. These
      biogenic amines are known to affect the virulence of infective pathogens and
      contribute to vaginal malodor. Our data suggest that cigarette smoking is
      associated with differences in important vaginal metabolites, and women who
      smoke, and particularly women who are also depauperate for Lactobacillus spp.,
      may have increased susceptibilities to urogenital infections and increased
      malodor.

PMID- 29339824
TI  - Oral microbiota of periodontal health and disease and their changes after
      nonsurgical periodontal therapy.
AB  - This study examined the microbial diversity and community assembly of oral
      microbiota in periodontal health and disease and after nonsurgical periodontal
      treatment. The V4 region of 16S rRNA gene from DNA of 238 saliva and subgingival
      samples of 21 healthy and 48 diseased subjects was amplified and sequenced. Among
      1979 OTUs identified, 28 were overabundant in diseased plaque. Six of these taxa
      were also overabundant in diseased saliva. Twelve OTUs were overabundant in
      healthy plaque. There was a trend for disease-associated taxa to decrease and
      health-associated taxa to increase after treatment with notable variations among
      individual sites. Network analysis revealed modularity of the microbial
      communities and identified several health- and disease-specific modules.
      Ecological drift was a major factor that governed community turnovers in both
      plaque and saliva. Dispersal limitation and homogeneous selection affected the
      community assembly in plaque, with the additional contribution of homogenizing
      dispersal for plaque within individuals. Homogeneous selection and dispersal
      limitation played important roles, respectively, in healthy saliva and diseased
      pre-treatment saliva between individuals. Our results revealed distinctions in
      both taxa and assembly processes of oral microbiota between periodontal health
      and disease. Furthermore, the community assembly analysis has identified
      potentially effective approaches for managing periodontitis.

PMID- 29339826
TI  - Using intracellular markers to identify a novel set of surface markers for live
      cell purification from a heterogeneous hIPSC culture.
AB  - Human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) can
      provide sources for midbrain dopaminergic (mDA) neural progenitors (NPCs) for
      cell therapy to treat Parkinson's disease (PD) patients. However, the well-known
      line-to-cell line variability in the differentiation capacity of individual cell
      lines needs to be improved for the success of this therapy. To address this
      issue, we sought to identify mDA NPC specific cell surface markers for
      fluorescence activated cell sorting (FACS). Through RNA isolation after sorting
      for NPCs based on staining for cell-specific transcription factors followed by
      microarray, we identified two positive cell surface markers (CORIN and CD166) and
      one negative cell surface marker (CXCR4) for mDA NPC sorting. These three markers
      can enrich floor plate NPCs to 90% purity, and the sorted NPCs more efficiently
      differentiate to mature dopaminergic neurons compared to unsorted or CORIN+ alone
      mDA NPCs. This surface marker identification strategy can be used broadly to
      facilitate isolation of cell subtypes of interest from heterogeneous cultures.

PMID- 29339825
TI  - Corallivory and the microbial debacle in two branching scleractinians.
AB  - The grazing activity by specific marine organisms represents a growing threat to
      the survival of many scleractinian species. For example, the recent proliferation
      of the corallivorous gastropod Drupella now constitutes a critical case in all
      South-East Asian waters. If the damaging effects caused by this marine snail on
      coral polyps are relatively well known, the indirect incidence of predation on
      coral microbial associates is still obscure and might also potentially impair
      coral health. In this study, we compared the main ecological traits of coral
      associated bacterial and viral communities living in the mucus layer of Acropora
      formosa and Acropora millepora, of healthy and predated individuals (i.e.,
      colonized by Drupella rugosa), in the Bay of Van Phong (Vietnam). Our results
      show a substantial impact of the gastropod on a variety of microbiological
      markers. Colonized corals harbored much more abundant and active epibiotic
      bacteria whose community composition shifted toward more pathogenic taxa
      (belonging to the Vibrionales, Clostridiales, Campylobacterales, and
      Alteromonadales orders), together with their specific phages. Viral epibionts
      were also greatly influenced by Drupella corallivory with spectacular
      modifications in their concentrations, life strategies, genotype richness, and
      diversity. Novel and abundant circular Rep-encoding ssDNA viruses (CRESS-DNA
      viruses) were detected and characterized in grazed corals and we propose that
      their occurrence may serve as indicator of the coral health status. Finally, our
      results reveal that corallivory can cause severe dysbiosis by altering virus
      bacteria interactions in the mucus layer, and ultimately favoring the development
      of local opportunistic infections.

PMID- 29339827
TI  - The impact of SO2 on wine flavanols and indoles in relation to wine style and
      age.
AB  - Wine has one of the broadest chemical profiles, and the common oenological
      practice of adding the antioxidant and antimicrobial sulfur dioxide has a major
      impact on its metabolomic fingerprint. In this study, we investigated novel
      discovered oenological reactions primarily occurring between wine metabolites and
      sulfur dioxide. The sulfonated derivatives of epicatechin, procyanidin B2, indole
      acetic acid, indole lactic acid and tryptophol were synthesized and for the first
      time quantified in wine. Analysis of 32 metabolites in 195 commercial wines (1986
      2016 vintages) suggested that sulfonation of tryptophan metabolites characterised
      white wines, in contrast to red wines, where sulfonation of flavanols was
      preferred. The chemical profile of the oldest wines was strongly characterised by
      sulfonated flavanols and indoles, indicating that could be fundamental
      metabolites in explaining quality in both red and white aged wines. These
      findings offer new prospects for more precise use of sulfur dioxide in
      winemaking.

PMID- 29339828
TI  - Fish consumption and depression in Korean adults: the Korea National Health and
      Nutrition Examination Survey, 2013-2015.
AB  - BACKGROUND/OBJECTIVES: There is a growing body of evidence that supports the
      potential role of fish consumption in relation to depression, but the data in
      Korean population is scarce. Thus, we examined the association between fish
      consumption and depression in Korean adults. SUBJECTS/METHODS: We conducted a
      cross-sectional study in 9183 Korean adults aged 19-64 years who participated in
      the 6TH Korea National Health and Nutrition Examination Survey (2013-2015), which
      is a large nationally representative study of Korean population. Fish consumption
      and depression status were assessed using questionnaires. Multivariable logistic
      regression models were used to compute odds ratios (ORs) and 95% confidence
      intervals (CIs) for physician-diagnosed clinical depression. RESULTS: Out of the
      9183 subjects, 389 (4.2%) were diagnosed with depression. After adjusting for
      potential confounders, the multivariable-adjusted ORs for clinical depression
      across fish consumption were 1.00 (reference) for <1 time/week, 0.76 (95% CI:
      0.56-1.04) for 1-3 times/week and 0.52 (95% CI: 0.37-0.74) for >=4 times/week (P
      for trend = 0.0005). The inverse association for >=4 times/week of fish
      consumption was stronger in women (OR = 0.44, 95% CI: 0.29-0.67, P for trend <
      .0001), but there was no significant association in men. CONCLUSIONS: Our
      findings suggest that high consumption of fish is associated with lower odds of
      depression in Korean adults, particularly in women. These results warrant further
      prospective studies to verify the association between fish consumption and risk
      of depression in Korean adults.

PMID- 29339829
TI  - Associations of the dietary approaches to stop hypertension (DASH) diet with
      pregnancy complications in Project Viva.
AB  - BACKGROUND/OBJECTIVES: The Dietary Approaches to Stop Hypertension (DASH) diet
      has been shown to improve cardiometabolic outcomes in non-pregnant populations.
      Little is known regarding the impact of this diet on health during pregnancy. The
      objective of this research is to examine associations of adherence to the DASH
      diet with hypertensive disorders of pregnancy (HDP) and other pregnancy outcomes.
      SUBJECTS/METHODS: We conducted analyses with data that came from 1760 women in
      Project Viva, a Boston-area longitudinal cohort recruited in early pregnancy 1999
      2002. We derived a DASH score using data from a food frequency questionnaire
      (FFQ) administered at median 11.1 weeks gestation. Next, we used multivariable
      linear regression models that accounted for the woman's age at enrollment, pre
      pregnancy body mass index (BMI), education, smoking habits, race/ethnicity,
      gestational weight gain (GWG) up until the time of the FFQ, and total energy
      intake to examine associations of the DASH score with HDP, gestational diabetes,
      preterm delivery (<37 weeks), birth size, and GWG from FFQ to delivery. Models
      for HDP and GDM were additionally mutually adjusted for each other. Because pre
      pregnancy weight status may modify these relationships, we tested for
      interactions between pre-pregnancy BMI and the DASH score. RESULTS: Mean +/- SD
      age of the women was 32.2 +/- 4.9 years; 71.9% were white. Overall, the DASH diet
      score (mean: 24.0, SD: 5.0) was not associated with any of the pregnancy outcomes
      or complications. However, we found a positive association between the DASH diet
      and subsequent GWG among women who were obese before pregnancy (0.19 [95% CI:
      0.05, 0.34], P <= 0.05 kg higher GWG per 1 unit DASH score). CONCLUSIONS:
      Adherence to DASH diet during early pregnancy does not appear to be protective
      against HDP or other adverse pregnancy outcomes.

PMID- 29339830
TI  - Differential association of dietary carbohydrate intake with metabolic syndrome
      in the US and Korean adults: data from the 2007-2012 NHANES and KNHANES.
AB  - BACKGROUND/OBJECTIVES: The risk factors for metabolic syndrome may differ between
      Western and Asian countries due to their distinct dietary cultures. However, few
      studies have directly compared macronutrient intake and its association with the
      risk of metabolic syndrome in the US and Korean adults using national survey
      data. SUBJECT/METHODS: Based on the data from the US and Korean versions of the
      2007-2012 National Health and Nutrition Examination Survey (NHANES, KNHANES), a
      total of 3,324 American and 20,515 Korean adults were included. In both
      countries, dietary intake was measured using a 24-h dietary recall method and
      metabolic syndrome was defined using the National Cholesterol Education Program
      Adult Treatment Panel III criteria. RESULTS: The percentages of energy intake
      from carbohydrate, protein, and fat were 50:16:33 in the US adults and 66:15:19
      in the Korean adults. Regarding metabolic abnormalities, Korean adults in the
      highest quintile of carbohydrate intake showed an increased risk of metabolic
      syndrome in men and women, with abnormalities of reduced HDL cholesterol and
      elevated triglyceride levels. In contrast, the US men showed no significant
      association with metabolic syndrome and its abnormalities, while the US women
      showed an increased risk of reduced HDL cholesterol and elevated triglycerides.
      CONCLUSIONS: A high carbohydrate intake is associated with metabolic
      abnormalities. As Korean adults consume more carbohydrate than American adults,
      stronger associations of dietary carbohydrate with metabolic syndrome were
      observed. Thus, further studies are necessary to elucidate the underlying
      mechanisms of different contributors to developing metabolic disease in Western
      and Asian populations.

PMID- 29339831
TI  - Detection of antimicrobial resistance genes associated with the International
      Space Station environmental surfaces.
AB  - Antimicrobial resistance (AMR) is a global health issue. In an effort to minimize
      this threat to astronauts, who may be immunocompromised and thus at a greater
      risk of infection from antimicrobial resistant pathogens, a comprehensive study
      of the ISS "resistome' was conducted. Using whole genome sequencing (WGS) and
      disc diffusion antibiotic resistance assays, 9 biosafety level 2 organisms
      isolated from the ISS were assessed for their antibiotic resistance. Molecular
      analysis of AMR genes from 24 surface samples collected from the ISS during 3
      different sampling events over a span of a year were analyzed with Ion AmpliSeqTM
      and metagenomics. Disc diffusion assays showed that Enterobacter bugandensis
      strains were resistant to all 9 antibiotics tested and Staphylococcus
      haemolyticus being resistant to none. Ion AmpliSeqTM revealed that 123 AMR genes
      were found, with those responsible for beta-lactam and trimethoprim resistance
      being the most abundant and widespread. Using a variety of methods, the genes
      involved in antimicrobial resistance have been examined for the first time from
      the ISS. This information could lead to mitigation strategies to maintain
      astronaut health during long duration space missions when return to Earth for
      treatment is not possible.

PMID- 29339833
TI  - The 'known-knowns', and 'known-unknowns' of extracellular Nm23-H1/NDPK proteins.
AB  - Nucleoside diphosphate kinases (NDPKs/NDK/NME) are a multifunctional class of
      proteins conserved throughout evolution. Whilst many of the functions of NDPKs
      have been identified as intracellular, extracellular eukaryotic and prokaryotic
      NDPK proteins are also detected in multiple systems and have been implicated in
      both normal physiology and disease. This review provides an overview of where the
      field stands on our developing understanding of how NDPK proteins get out of
      cells, the physiological role of extracellular NDPKs, and how extracellular NDPKs
      may signal to cells. We will also discuss some of the unanswered questions, the
      'known-unknowns' that particularly warrant further investigation.

PMID- 29339832
TI  - CLOCKDelta19 mutation modifies the manner of synchrony among oscillation neurons
      in the suprachiasmatic nucleus.
AB  - In mammals, the principal circadian oscillator exists in the hypothalamic
      suprachiasmatic nucleus (SCN). In the SCN, CLOCK works as an essential component
      of molecular circadian oscillation, and ClockDelta19 mutant mice show unique
      characteristics of circadian rhythms such as extended free running periods,
      amplitude attenuation, and high-magnitude phase-resetting responses. Here we
      investigated what modifications occur in the spatiotemporal organization of clock
      gene expression in the SCN of ClockDelta19 mutants. The cultured SCN, sampled
      from neonatal homozygous ClockDelta19 mice on an ICR strain comprising
      PERIOD2::LUCIFERASE, demonstrated that the Clock gene mutation not only extends
      the circadian period, but also affects the spatial phase and period distribution
      of circadian oscillations in the SCN. In addition, disruption of the
      synchronization among neurons markedly attenuated the amplitude of the circadian
      rhythm of individual oscillating neurons in the mutant SCN. Further, with
      numerical simulations based on the present studies, the findings suggested that,
      in the SCN of the ClockDelta19 mutant mice, stable oscillation was preserved by
      the interaction among oscillating neurons, and that the orderly phase and period
      distribution that makes a phase wave are dependent on the functionality of CLOCK.

PMID- 29339834
TI  - Use of multicolor fluorescence in situ hybridization to detect deletions in
      clinical tissue sections.
AB  - A variety of laboratory methods are available for the detection of deletions of
      tumor suppressor genes and losses of their proteins. The clinical utility of
      fluorescence in situ hybridization (FISH) for the identification of deletions of
      tumor suppressor genes has previously been limited by difficulties in the
      interpretation of FISH signal patterns. The first deletion FISH assays using
      formalin-fixed paraffin-embedded tissue sections had to deal with a significant
      background level of signal losses affecting nuclei that are truncated by the
      cutting process of slide preparation. Recently, more efficient probe designs,
      incorporating probes adjacent to the tumor suppressor gene of interest, have
      increased the accuracy of FISH deletion assays so that true chromosomal deletions
      can be readily distinguished from the false signal losses caused by sectioning
      artifacts. This mini-review discusses the importance of recurrent tumor
      suppressor gene deletions in human cancer and reviews the common FISH methods
      being used to detect the genomic losses encountered in clinical specimens. The
      use of new probe designs to recognize truncation artifacts is illustrated with a
      four-color PTEN FISH set optimized for prostate cancer tissue sections. Data are
      presented to show that when section thickness is reduced, the frequency of signal
      truncation losses is increased. We also provide some general guidelines that will
      help pathologists and cytogeneticists run routine deletion FISH assays and
      recognize sectioning artifacts. Finally, we summarize how recently developed
      sequence-based approaches are being used to identify recurrent deletions using
      small DNA samples from tumors.

PMID- 29339835
TI  - Obtaining high quality transcriptome data from formalin-fixed, paraffin-embedded
      diagnostic prostate tumor specimens.
AB  - Prognostic genomic biomarkers that can be measured at diagnosis to aid choice of
      treatment options are unavailable for most common cancers. This is due in part to
      the poor quality and quantity of available diagnostic specimens for discovery
      research and to limitations in genomic technologies. Recent technical advances
      now enable high-density molecular analyses using suboptimal biological specimens.
      Here we describe the optimization of a transcriptome-specific protocol for use
      with formalin-fixed, paraffin-embedded (FFPE) diagnostic prostate cancer (PrCa)
      specimens. We applied the Ion AmpliSeq Transcriptome Human Gene Expression Kit
      (AmpliSeq Kit) to RNA samples extracted from 36 tumor-enriched and 16 adjacent
      normal tissues (ADJNT) from 37 FFPE PrCa specimens over a series of eight pilot
      studies, incorporating protocol modifications from Pilots 2 to 5. Data quality
      were measured by (1) the total number of mapped reads; (2) the percentage of
      reads that mapped to AmpliSeq target regions (OnTarget%); (3) the percentage of
      genes on the AmpliSeq panel with a read count >=10 (TargetsDetected%); and (4)
      comparing the gene read-count distribution of the prostate tissue samples with
      the median gene read-count distribution of cell line-derived RNA samples.
      Modifications incorporated into Pilot study 5 provided gene expression data
      equivalent to cell line-derived RNA samples. These modifications included the use
      of freshly cut slides for macrodissection; increased tissue section thickness (8
      um); RNA extraction using the RecoverAll Total Nucleic Acid Isolation Kit for
      FFPE (ThermoFisher); 18 target amplification cycles; and processing six samples
      per Ion PI chip. This protocol will facilitate the discovery of prognostic
      biomarkers for cancer by allowing researchers to exploit previously underutilized
      diagnostic FFPE specimens.

PMID- 29339836
TI  - The role of metabolic enzymes in mesenchymal tumors and tumor syndromes:
      genetics, pathology, and molecular mechanisms.
AB  - The discovery of mutations in genes encoding the metabolic enzymes isocitrate
      dehydrogenase (IDH), succinate dehydrogenase (SDH), and fumarate hydratase (FH)
      has expanded our understanding not only of altered metabolic pathways but also
      epigenetic dysregulation in cancer. IDH1/2 mutations occur in enchondromas and
      chondrosarcomas in patients with the non-hereditary enchondromatosis syndromes
      Ollier disease and Maffucci syndrome and in sporadic tumors. IDH1/2 mutations
      result in excess production of the oncometabolite (D)-2-hydroxyglutarate. In
      contrast, SDH and FH act as tumor suppressors and genomic inactivation results in
      succinate and fumarate accumulation, respectively. SDH deficiency may result from
      germline SDHA, SDHB, SDHC, or SDHD mutations and is found in autosomal-dominant
      familial paraganglioma/pheochromocytoma and Carney-Stratakis syndrome, describing
      the combination of paraganglioma and gastrointestinal stromal tumor (GIST). In
      contrast, patients with the non-hereditary Carney triad, including paraganglioma,
      GIST, and pulmonary chondroma, usually lack germline SDH mutations and instead
      show epigenetic SDH complex inactivation through SDHC promoter methylation.
      Inactivating FH germline mutations are found in patients with hereditary
      leiomyomatosis and renal cell cancer (HLRCC) syndrome comprising benign
      cutaneous/uterine leiomyomas and renal cell carcinoma. Mutant IDH, SDH, and FH
      share common inhibition of alpha-ketoglutarate-dependent oxygenases such as the
      TET family of 5-methylcytosine hydroxylases preventing DNA demethylation, and
      Jumonji domain histone demethylases increasing histone methylation, which
      together inhibit cell differentiation. Ongoing studies aim to better characterize
      these complex alterations in cancer, the different clinical phenotypes, and
      variable penetrance of inherited and sporadic cancer predisposition syndromes. A
      better understanding of the roles of metabolic enzymes in cancer may foster the
      development of therapies that specifically target functional alterations in tumor
      cells in the future. Here, the physiologic functions of these metabolic enzymes,
      the mutational spectrum, and associated functional alterations will be discussed,
      with a focus on mesenchymal tumor predisposition syndromes.

PMID- 29339837
TI  - Validation of the Brief International Cognitive Assessment for Multiple Sclerosis
      in Japan.
AB  - Background: The Brief International Cognitive Assessment for MS (BICAMS) is a
      practical battery for measuring cognitive function in multiple sclerosis (MS).
      Objectives: We aimed to validate a Japanese version of the BICAMS in patients
      with MS and healthy controls. Methods: The Symbol Digit Modalities Test (SDMT),
      the California Verbal Learning Test-Second Edition (CVLT2) and the Brief
      Visuospatial Memory Test Revised (BVMTR) were administered to 156 patients with
      MS and 126 healthy controls (HCs). The BICAMS was re-administered in a subset of
      27 MS patients and 30 HCs. Results: The mean (+/-SD) raw scores in the MS and HC
      groups were as follows: SDMT: MS 47.9 +/- 14.0, HC 61.0 +/- 9.5; CVLT2: MS 48.6
      +/- 12.6, HC 55.7 +/- 10.5; BVMTR: MS 23.5 +/- 8.4, HC 28.3 +/- 5.4,
      respectively, and significant differences were found between the two groups on
      all tests (p < 0.0001). Cohen's d values were 1.07, 0.60, and 0.67 in SDMT,
      CVLT2, and BVMTR, respectively. The test-retest reliability coefficients for each
      test were as follows: SDMT: r = 0.93; CVLT2: r = 0.82; and BVMTR: r = 0.77 (p <
      0.0001). Conclusions: This study provides results that support the reliability
      and validity of the BICAMS in Japan.

PMID- 29339838
TI  - Force and Scale Dependence of the Elasticity of Self-Assembled DNA Bottle
      Brushes.
AB  - As a model system to study the elasticity of bottle-brush polymers, we here
      introduce self-assembled DNA bottle brushes, consisting of a DNA main chain that
      can be very long and still of precisely defined length, and precisely
      monodisperse polypeptide side chains that are physically bound to the DNA main
      chains. Polypeptide side chains have a diblock architecture, where one block is a
      small archaeal nucleoid protein Sso7d that strongly binds to DNA. The other block
      is a net neutral, hydrophilic random coil polypeptide with a length of exactly
      798 amino acids. Light scattering shows that for saturated brushes the grafting
      density is one side chain per 5.6 nm of DNA main chain. According to small-angle
      X-ray scattering, the brush diameter is D = 17 nm. By analyzing configurations of
      adsorbed DNA bottle brushes using AFM, we find that the effective persistence of
      the saturated DNA bottle brushes is Peff = 95 nm, but from force-extension curves
      of single DNA bottle brushes measured using optical tweezers we find Peff = 15
      nm. The latter is equal to the value expected for DNA coated by the Sso7d binding
      block alone. The apparent discrepancy between the two measurements is
      rationalized in terms of the scale dependence of the bottle-brush elasticity
      using theory previously developed to analyze the scale-dependent electrostatic
      stiffening of DNA at low ionic strengths.

PMID- 29339839
TI  - Trends in trauma-related mortality among adolescents: A 6 year snapshot from a
      teaching hospital's post mortem data.
AB  - Introduction: The aim is to explore the trends in trauma mortality in children
      aged 0-18 years can help to co-ordinate resources toward research and programs to
      reduce the burden. Methods: This is a retrospective study carried out on
      adolescents <=18 years of age autopsied according to the attorney request at
      Forensic Medicine & Toxicology department of King George's Medical University,
      Lucknow, India in the period from January 1st, 2009 to December 31st, 2014.
      Results: There were 9160 deaths from all causes in children <=18 years old, 7747
      of which were due to trauma related causes, with a female predominance of 1.3:1.
      The age distribution revealed that 65.8% of deaths occurred in the 10-18 age
      group. Road traffic accidents (RTA) was the most prevalent cause (3635 deaths -
      46.92%), followed by asphyxia (1128 deaths - 14.56%) and sexual assault (649
      deaths - 8.37%). Asphyxia/suffocation was the major cause of injury with 31.96%
      of deaths within group <1 year; asphyxia (28.66%) and transport-related injuries
      (32.27%) were more predominant in the 1-4 age group; transport-related deaths
      were frequent in the 5-9 age group (45.14%), 10-14 age group (55.68%) and in the
      group 15-18 age group (51.69%). Regarding times of death, 61% occurred at the
      scene, 5.6% during pre-hospital care, 26.2% occurred at the hospital within the
      first 24 h after admission, and the remaining 7.6% of deaths occurred after 24 h
      after admission to the hospital. When we analyzed the deaths according to the
      intent, homicides occurred in 16% of cases. Unintentional injuries occurred in
      69% of deaths and self-inflicted injuries were identified in 15% cases.
      Conclusions: Findings show that there was a predominance of deaths in children
      and adolescents males, between 15 and 18 years old, mainly from road traffic
      accidents. This study highlights the burden of trauma caused mortalities in
      children, which requires instant action.

PMID- 29339840
TI  - Complex knee injury scenario in tertiary level care in North India: An
      epidemiological study.
AB  - : Floating knee injury has been considered as one of the severe orthopedic
      injury, and is often associated with major systemic trauma involving other
      organs. Objective: To identify the incidence of floating knee injury, severity of
      injury and associated orthopaedic and non-orthopaedic injury. Methods:
      Epidemiologic study conducted from 1 Jan 2014 to 31 Dec 2014. Results: A total of
      136 cases with floating knee injury were registered. Modified Fraser
      classification showed 58 patients had type 1, 74 had type 2 and 4 had type 3
      floating knees. 119(87.5%) patients had open fractures and Gustilo-Anderson type
      IIIA(29.4%) being the commonest. No Mortality was found. 16 (11.76%) of floating
      knees had to undergo amputation of afflicted limb. Conclusion: Statics of such
      data would be helpful in planning and preparing ourselves as healthcare
      professionals to prevent high mortality and morbidity/disability in floating knee
      injury. Study design: Retrospective Epidemiological. Level of Evidence: Level 4
      (Case Study).

PMID- 29339841
TI  - Role of autologous non-vascularised intramedullary fibular strut graft in humeral
      shaft nonunions following failed plating.
AB  - Background: Non-union humeral shaft fractures are seen frequently in clinical
      practice at about 2-10% in conservative management and 30% in surgically operated
      patients. Osteosynthesis using dynamic compression plate (DCP), intramedullary
      nailing, locking compression plate (LCP), Ilizarov technique along with bone
      grafting have been reported previously. In cases of prior failed plate-screw
      osteosynthesis the resultant osteopenia, cortical defect, bone loss, scalloping
      around screws and metallosis, make the management of non-union more complicated.
      Fibular graft as an intramedullary strut is useful in these conditions by
      increasing screw purchase, union and mechanical stability. This study is a
      retrospective and prospective follow up of revision plating along with autologous
      non-vascularised intramedullary fibular strut graft (ANVFG) for humeral non
      unions following failed plate osteosynthesis. Materials and methods: Seventy
      eight cases of nonunion humeral shaft fractures were managed in our institute
      between 2008 and 2015. Of these, 57 cases were failed plate osteosynthesis, in
      which 15 cases were infected and 42 cases were noninfected. Out of the 78 cases,
      bone grafting was done in 55 cases. Fibular strut graft was used in 22 patients,
      of which 4 cases were of primary nonunion with osteoporotic bone. Applying the
      exclusion criteria of infection and inclusion criteria of failed plate
      osteosynthesis managed with revision plating using either LCP or DCP and ANVFG,
      17 cases were studied. The mean age of the patients was 40.11 yrs (range: 26-57
      yrs). The mean duration of non-union was 4.43 yrs (range: 0.5-14 yrs). The mean
      follow-up period was 33.41 months (range: 12-94 months). The average length of
      fibula was 10.7 cm (range: 6-15 cm). Main outcome measurements included bony
      union by radiographic assessment and pre- and postoperative functional evaluation
      using the DASH (Disabilities of the Arm, Shoulder and Hand) score. Results:
      Sixteen out of 17 fractures united following revision plating and fibular strut
      grafting. Average time taken for union was 3.5 months (range: 3-5 months).
      Complications included one each of implant failure with bending, transient radial
      nerve palsy and transient ulnar nerve palsy. No case had infection, graft site
      morbidity or peroneal nerve palsy. Functional assessment by DASH score improved
      from 59.14 (range: 43.6-73.21) preoperatively to 23.39 (range: 8.03-34.2)
      postoperatively (p = 0.0003). Conclusion: The results of our study indicate that
      revision plating along with ANVFG is a reliable option in humeral diaphyseal non
      unions with failed plate-screw osteosynthesis providing adequate screw purchase,
      mechanical stability and high chances of union with good functional outcome.

PMID- 29339842
TI  - The clinico-radiological outcome of open reduction and internal fixation of
      displaced scaphoid fractures in the adult age group.
AB  - Background: Scaphoid fracture is the most common among carpal bone fractures,
      frequently imperceptible on initial radiographs. Tendency of scaphoid fracture to
      undergo in non-union makes it an important challenging injury for all orthopaedic
      surgeons. Displaced scaphoid fracture has high non-union rate in conservative
      management asserting the need to explore operative treatment. Materials and
      method: A prospective study was conducted in our institution in thirty patients
      in 20 to 50 year age group, for displaced scaphoid fracture (<30 days duration).
      Patient were followed up at every 4 week interval for 6 month and then three
      monthly for total duration of 18 months. At each follow up clinical and
      functional outcome was measured by Mayo wrist score and Patient rated wrist
      evaluation, and radiological outcome was measured in terms of union. Results:
      Mayo wrist score showed satisfactory outcome at 8 week, and good and excellent
      outcome at 12 week and 16 week period. Patient rated wrist score showed
      improvement in clinical and functional result at three month period. Conclusions:
      The use of open reduction and internal fixation by Herbert screw in acute
      displaced scaphoid fracture has good clinical, functional, and radiological
      outcome, and associated with early recovery.

PMID- 29339843
TI  - Distal radius re-fracture with bending of implant and neurovascular compromise.
AB  - Peri-implant fractures of the wrist are uncommon, and usually present as stress
      fractures distal to the site of the implant. We report an unusual case where the
      radius has fractured beneath a plate, causing bending and deformity of the
      implant. This prevented reduction of the fracture under sedation, so urgent
      intervention became necessary due to neurovascular compromise.

PMID- 29339844
TI  - The risk of deep vein thrombosis in total joint patients compared to orthopaedic
      trauma patients: Need for new prevention guidelines.
AB  - Background: The development of Deep Vein Thrombosis (DVT) is a major concern
      following orthopaedic surgery. No study has yet to compare the rate and risk
      factors for DVT between total joint and orthopaedic trauma patients. To evaluate
      if DVT prophylaxis for trauma should differ from total joints, we explored the
      rate and risk factors for DVT between both cohorts. Methods: Using a CPT code
      search from 2005 to 2013 in the ACS-NSQIP database, 150,657 orthopaedic total
      joint patients and 44,594 orthopaedic trauma patients were identified. DVT
      complications, patient demographics, preoperative comorbidities, and surgical
      characteristics were collected for each patient. A chi-squared test was used to
      compare the risk factors for DVT between orthopaedic trauma and total joint
      patients. A multivariable logistic regression model was built to adjust for
      comorbidities for each cohort. Results: The rate of DVT diagnosis in the total
      joint population was 0.8% (N = 1186) and 0.98% (N = 432) in the orthopaedic
      trauma population (p = 0.57). After controlling for individual comorbidities,
      dyspnea, peripheral vascular disease, and renal failure were significant risk
      factors for DVT in total joint patients (p < 0.05), whereas age, ascites and
      steroid use were significant risk factors for DVT in orthopaedic trauma patients
      (p < 0.05). Conclusions: Historically, the risks for DVT in total joints have
      been emphasized, yet based on our results, the incidence of DVT is the same for
      orthopaedic trauma. However, the risk factors varied. It is therefore important
      to consider specialty-specific DVT prophylaxis for orthopaedic trauma patients in
      order to improve care and reduce postoperative complications.

PMID- 29339845
TI  - Incidence of spinal fractures in the Netherlands 1997-2012.
AB  - : : To determine time trends of emergency department (ED) visits, hospitalization
      rates, spinal cord lesions and characteristics of patients with spinal fractures
      in the Netherlands. METHODS: In an observational database study we used the Dutch
      Injury Surveillance System to analyse spinal fracture-related ED visits,
      hospitalization rates and spinal cord lesions between 1997 and 2012. RESULTS: The
      total number of ED visits associated with spinal fractures increased from 4,507
      in 1997 to 9,690 in 2012 (115% increase). The increase in the total number of
      fractures occurred in all age groups independently of gender. However, incidence
      rates increased more strongly with age and were higher in young males and ageing
      females. The hospitalization rate of diagnosed spinal fractures remained stable
      between 62 and 67%. The incidence of spinal cord lesions varied between 13.8 and
      20.3 per million of the population over a period of 15 years. CONCLUSION: Spinal
      fracture-related ED visits are increasing in the Dutch population, independently
      of age or gender. The hospitalization rate and the absolute numbers of spinal
      cord lesions have remained stable over a period of 15 years. These findings are
      relevant for public health decision-making and resource allocation.

PMID- 29339846
TI  - Ankle arthrodesis-Open versus arthroscopic: A systematic review and meta
      analysis.
AB  - Objectives: Our objective was to perform a systematic review of the literature
      and conduct a meta-analysis to investigate the outcomes of open versus
      arthroscopic methods of ankle fusion. Methods: In accordance with Preferred
      Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement
      standards, we performed a systematic review. Electronic databases MEDLINE,
      EMBASE, CINAHL and the Cochrane Central Register of Controlled Trials (CENTRAL)
      were searched to identify randomised and non-randomised studies comparing
      outcomes of arthroscopic and open ankle arthrodesis. The Newcastle-Ottawa scale
      was used to assess the methodological quality and risk of bias of the selected
      studies. Fixed-effect or random-effects models were applied to calculate pooled
      outcome data. Results: We identified one prospective cohort study and 5
      retrospective cohort studies, enrolling a total of 286 patients with ankle
      arthritis. Our analysis showed that open ankle fusion was associated with a lower
      fusion rate (OR 0.26, 95% CI 0.13-0.52, P = 0.0002), longer tourniquet time (MD
      16.49, 95% CI 9.46-23.41, P < 0.00001), and longer length of stay (MD 1.60,95% CI
      1.10-2.10, P < 0.00001) compared to arthroscopic ankle fusion; however, there was
      no significant difference between two groups in terms of infection rate (OR 2.41,
      95% CI 0.76-7.64, P = 0.14), overall complication rate (OR: 1.54, 95% CI 0.80
      2.96, P = 0.20), and operation time (MD 4.09, 95% CI -2.49-10.66, P = 0.22). The
      between-study heterogeneity was high for tourniquet time but low or moderate for
      other outcomes. The direction of the effect sizes remains unchanged throughout
      sensitivity analyses. Conclusions: The best available evidence demonstrates that
      arthroscopic ankle fusion may be associated with a higher fusion rate, shorter
      tourniquet time, and shorter length of stay compared to open ankle fusion. We
      found no significant difference between two groups in terms of infection rate,
      overall complication rate, and operation time. The best available evidence is not
      adequately robust to make definitive conclusions. Long-term results of the
      comparative efficacy of arthroscopic ankle fusion over open ankle fusion are not
      currently available. Further high quality randomised controlled trials that are
      adequately powered are required.

PMID- 29339847
TI  - Giant extraskeletal osteochondroma of foot. A case report with review of
      literature.

PMID- 29339848
TI  - Habitual patellar dislocation in children: Results of surgical treatment by
      modified four in one technique.
AB  - Background: Habitual patellar dislocation is a rare condition affecting children.
      The growth plates are open in children and any surgical intervention should take
      that in to consideration. We are describing a modified four in one technique for
      habitual patellar dislocation, which is a soft tissue procedure without the use
      of any implant. Method: In this study we included 6 children (4 females and 2
      males) with open growth plates, which were diagnosed with habitual patellar
      dislocation. The average age of the patients were 9.6 years (range 5-13 years).
      Our technique included lateral retinaculum release, vastus medialis obliques
      (VMO) advancement, partial patellar tendon transposition and reconstruction of
      medial patellofemoral ligament (MPFL). Patients were evaluated with Kujala
      scoring pre and post operatively. The average follow up period was 12 months
      (range 7-24 months). Results: There were no recurrence of patellar instability in
      any of the cases. The mean Kujala score was 48 before surgery and it improved to
      95 after 12 months of average follow-up after surgery. Conclusion: We conclude
      that our method of treatment of habitual patellar dislocation by using modified
      four in one technique in children with open physis reproduced excellent
      functional outcome. It is simple, cheap and does not require any image guidance.
      Therapeutic study: Level of evidence IV.

PMID- 29339849
TI  - Can an exostosis be free floating without any continuity to the underlying bone:
      A diagnostic dilemma.
AB  - : Osteochondroma or exostosis is the most common primary bone tumor containing
      both bone and cartilage. Soft tissue osteochondromas have been described at
      various locations, however, to the best of our knowledge, there is only a single
      case report of a soft tissue osteochondroma around the femoral neck. We, hereby
      report second such case. CASE REPORT: A forty year old female presented with
      swelling on medial aspect of left thigh since four years. Radiographs showed a
      large mass at the inferior surface of the left femoral neck. CT scan revealed a
      well defined lobulated mass lesion involving muscles of adductor compartment of
      thigh. MRI showed lobulated periarticular, intramuscular, non enhancing lesion
      isointense to the bone, but without any continuity to the adjacent femur.
      Histopathology of the excised lesion turned out to be osteochondroma with origin
      from soft tissue. This case highlights an important differential diagnosis to be
      considered whenever an ossified mass is located in soft tissue.

PMID- 29339850
TI  - Giant cell tumour of tendon sheath and synovial membrane: A review of 26 cases.
AB  - Aim: Aim of our study is to highlight the incidence and benign nature of Giant
      cell tumour of tendon sheath and need for complete removal, thus minimizing the
      chances of recurrence. Material and methods: A total of 26 cases of Giant cell
      tumour of tendon sheath operated in the department of Orthopaedics, Patna Medical
      College & Hospital, Patna from 2003 to 2010 were included in this study. The
      surgery was performed after clinical evaluation of the lesion and Fine Needle
      Aspiration Cytology (FNAC). The tumour underwent en bloc marginal excision. The
      patients were followed up for minimum two year. Results: Our study population
      consisted of 18 females and 8 males. The mean age at the time of surgery was 38.3
      years (range, 18-62 years). Twenty three cases were found in the 3rd and 4th
      decade. Twenty two cases involved upper extremity and only 4 cases in lower
      extremity. MRI was done in 2 cases where diagnosis was in doubt. Bony indentation
      on X-ray film was found in 7 cases and thorough curettage of cortical shell was
      done. All the cases were treated by marginal excision. Three cases developed post
      operative stiffness but regained full range of movement with physiotherapy.
      Sensory impairment was seen in 3 cases. Recurrence occurred in 2 case and they
      were treated by repeat marginal excision. Conclusion: Meticulous en-masse
      marginal excision of the giant cell tumour of tendon sheath in blood less field
      using magnification is the treatment of choice.

PMID- 29339851
TI  - Self-Report of Behaviors to Manage Neurogenic Bowel and Bladder by Individuals
      with Chronic Spinal Cord Injury: Frequency and Associated Outcomes.
AB  - Background: The management of neurogenic bowel and bladder by individuals with
      spinal cord injury (SCI) often requires a complicated set of behaviors to
      optimize functioning and reduce complications. However, limited research is
      available to support the many recommendations that are made. Objective: To
      describe the occurrence of behaviors associated with the management of neurogenic
      bowel and bladder among individuals with chronic SCI and to explore whether
      relationships exist between the performance of those behaviors and outcomes
      related to health and quality of life. Methods: A survey was developed based on
      clinical guidelines to collect self-report information about the performance of
      specific behaviors associated with the management of neurogenic bowel and bladder
      by individuals with SCI. It was administered to 246 individuals with chronic SCI
      living in the community as part of a larger ongoing study. Results: Results
      suggest that the methods that those with SCI use to manage neurogenic bowel and
      bladder are multifaceted. Many methods are performed with significant
      consistency, but significant variations exist for some and are often associated
      with neurological status, methods of evacuation, and quality of life. Conclusion:
      Many people with SCI of long duration are not sure of the sources of
      recommendations for some of the management activities that they or their personal
      care assistants conduct. It is prudent for clinicians working with these people
      to review their recommendations periodically to ensure that they are current and
      understood.

PMID- 29339852
TI  - Resilience and Happiness After Spinal Cord Injury: A Qualitative Study.
AB  - Objective: The purpose of this study was to identify factors associated with
      resilience among individuals with spinal cord injury (SCI). Methods: Qualitative
      analyses were conducted of the written comments that were completed as part of a
      cross-sectional survey of individuals with SCI living in the community. More than
      1,800 mail surveys were distributed to individuals identified as having a
      traumatic SCI through the records and/or membership lists of 4 organizations.
      Four hundred and seventy-five individuals completed and returned the survey, with
      approximately half (48.6%; n = 231) of respondents answering the open-ended
      question "Is there anything else you would like to tell us about your resilience
      or ability to 'bounce back' when you face a challenge?" Results: Analyses of
      these responses identified both specific resources and cognitive perspectives
      that are associated with perceived happiness. Responses fell within 8 general
      categories: resilience, general outlook on life, social support and social
      relationships, religion or faith in a higher power, mood, physical health and
      functioning (including pain), social comparisons, and resources. Nuanced themes
      within these categories were identified and were generally concordant with self
      reported level of happiness. Conclusion: A majority of respondents with SCI
      identified themselves as happy and explained their adjustment and resilience as
      related to personality, good social support, and a spiritual connection. In
      contrast, pain and physical challenges appeared to be associated with limited
      ability to bounce back.

PMID- 29339853
TI  - Impact of Health Behaviors and Health Management on Employment After SCI:
      Psychological Health and Health Management.
AB  - Objective: The purpose of this study was to examine the relationship between
      employment and psychological health and health management as described by
      individuals with spinal cord injury (SCI) who were employed at least once
      following injury. Methods: A qualitative approach used 6 focus groups at 2 sites
      with 44 participants who were at least 10 years post SCI. All had been employed
      at some point since injury. Heterogeneous and homogeneous groups were delineated
      based on specific characteristics, such as education, gender, or race. Group
      sessions followed a semi-structured interview format with questions about
      personal, environmental, and policy related factors influencing employment
      following SCI. All group sessions were recorded, transcribed, and coded into
      conceptual categories to identify topics, themes, and patterns. Inferences were
      drawn about their meaning. NVivo 10 software using the constant comparative
      method was used for data analysis. Results: Narratives discussed the relationship
      between employment and psychological and emotional health and health management.
      Four themes were identified: (1) adjustment and dealing with emotional reactions,
      (2) gaining self-confidence, (3) preventing burnout, and (4) attitudes and
      perspectives. Most themes reflected issues that varied based on severity of
      injury as well as stage of employment. Conclusions: Individuals with SCI who are
      successful in working following injury must determine how to perform the
      behaviors necessary to manage their health and prevent emotional or physical
      complications. The emotional consequences of SCI must be recognized and addressed
      and specific behaviors enacted in order to optimize employment outcomes.

PMID- 29339854
TI  - Development and Feasibility of Health Mechanics: A Self-Management Program for
      Individuals with Spinal Cord Injury.
AB  - Objective: We conducted a pilot study to examine the feasibility of administering
      an individual, in-person version of Health Mechanics, an innovative self
      management program designed to teach individuals with spinal cord injury (SCI) to
      maintain physical health and prevent secondary conditions. Methods: After
      baseline assessments, 27 participants were randomized using a 2:1 block design to
      either the experimental intervention or a usual care group. Thirteen of the 19
      participants in the intervention group completed the program. Follow-up
      assessments were completed at 3 and 6 months after baseline. Results: Results
      suggest that the Health Mechanics intervention delivered in an in-person format
      was perceived as useful and relevant in addressing a diverse range of health
      issues with participants with a wide range of personal and impairment
      characteristics. However, attrition rates and barriers to recruitment suggested
      limitations in the acceptability of the format for this population. Conclusion:
      Additional research is needed to identify the populations that would most benefit
      from the program and the most efficacious context for administration.

PMID- 29339855
TI  - Locomotor Training in the Pediatric Spinal Cord Injury Population: A Systematic
      Review of the Literature.
AB  - Background: The restoration of walking ability in the spinal cord injury (SCI)
      population is an increasingly important goal in physical therapy. Locomotor
      training (LT) is often implemented with the aim to restore ambulation. At this
      point, there are no guidelines for LT in the pediatric SCI population.
      Objectives: The aim of this review is to further narrow the effects of LT to the
      pediatric SCI population and develop recommendations for pediatric LT. Methods: A
      thorough search was performed using the following databases: Scopus, CINAHL,
      PubMed, and Ovid. Studies were selected based on the following inclusion
      criteria: pediatric SCI population, articles published within last 10 years,
      human subjects, and LT. Studies looking at other neurological disorders and
      subjects who were not previously ambulatory were excluded. Five students and one
      Faculty Research Advisor from the university's Doctor of Physical Therapy Program
      evaluated the inclusion criteria, conducted a risk of bias assessment using the
      Downs and Black checklist, and extracted the results. Results: Six studies were
      selected for this review. They showed gains in distance, gait speed, walking
      independence, and participation. There were variations in results when comparing
      gains in injury level based on the International Standards for Neurological
      Classification of Spinal Cord Injury (ISNCSCI). Conclusions: Currently there is
      insufficient evidence to determine the best clinical practice guidelines for
      rehabilitation using LT within the pediatric SCI population.

PMID- 29339856
TI  - Relationships Between Caregiver Characteristics and Health-Related Quality of
      Life Among Youth with Spinal Cord Injury.
AB  - Background: Past research has found a relationship between the mental health of
      parental caregivers and their children with spinal cord injury (SCI), but little
      is known about how other aspects of caregiver health and functioning impact
      health-related quality of life (HRQOL) of youth. Objective: The purpose of this
      study was to explore the importance of caregiver mental health, physical health,
      burden, and problem-solving skills in relation to children's physical and
      psychosocial HRQOL. Methods: Forty youths with SCI ages 7 to 17 years completed
      the PedsQLTM; primary caregivers completed standardized measures of mental and
      physical health, burden, and problem solving. We evaluated 2 hierarchical linear
      regression models predicting children's physical and psychosocial HRQOL. Results:
      The 40 youths were an average of 11.48 years (SD = 3.21), 62.5% were male, and
      80% Caucasian. They had been injured an average of 6.90 years (SD = 3.92); 75%
      had paraplegia, and 61.5% had complete injuries. Most caregivers were mothers
      (85%), were married (60%), and had at least some college education (87.5%).
      Univariate analyses revealed that caregiver problem solving alone was related to
      children's physical HRQOL, and caregiver mental health, burden, and problem
      solving were related to children's psychosocial HRQOL. Regression analyses
      controlling for child age and injury level revealed effective caregiver problem
      solving (P < .01) was significantly related to greater child physical (Model R2 =
      0.440) and psychosocial (Model R2 = 0.547) HRQOL. Conclusions: Although
      relationships should be explored longitudinally with larger samples, results
      indicate caregiver problem solving may be a reasonable target for intervention to
      improve HRQOL among youth with SCI.

PMID- 29339857
TI  - Comparison of Soleus H-Reflexes in Two Groups of Individuals With Motor
      Incomplete Spinal Cord Injury Walking With and Without a Walker.
AB  - Objective: To compare phase- and task-dependent H-reflex modulation in standing
      and walking in 2 spinal cord injury (SCI) groups with and without a walker.
      Methods: Fourteen subjects with American Spinal Injury Association Impairment
      Scale D SCI (40+/-10 years) participated. Tibial nerve was stimulated to evoke 15
      H-reflexes (at M-wave 7%-13% of maximum-M). Results: H-reflex was greater in the
      walker group during stance (but not standing/swing). Conclusion: Differences in H
      reflex modulation between groups walking with and without a walker may be
      explained by sensory mechanism that enhances central excitation, difference in
      motor activation levels between groups, and other complex mechanisms that
      influence balance or stability.

PMID- 29339858
TI  - Examining How the Perception of Health Can Impact Participation and Autonomy
      Among Adults with Spinal Cord Injury.
AB  - Background: Studies examining participation as defined by the International
      Classification of Functioning, Disability and Health (ICF) as well as autonomy
      among the spinal cord injury population (SCI) are only starting to emerge. Little
      research has looked at how this population perceives their health status and the
      role this plays in active participation within their lives. Objective: This
      exploratory study was developed to determine whether the perception of health has
      an impact on participation and autonomy among adults with SCI. Methods: A
      convenience sample of adults with SCI currently receiving outpatient services
      from a rehabilitation hospital completed the online questionnaire. Forty-two
      subjects responded and were categorized into 2 groups: Group 1, positive
      perceived health, and Group 2, negative perceived health. The sample completed
      the Impact on Autonomy and Participation (IPA) that has 5 subscales (autonomy
      indoors, family role, autonomy outdoors, social life, and work/education) and
      demographic questions. Results: Multivariate analysis of variance (MANOVA)
      revealed that perceived health had a significant impact on family roles, autonomy
      outdoors, social life, and work/education. Perceived health did not have a
      significant impact on autonomy indoors. Conclusion: The perception of health may
      have an impact on participation and autonomy within the areas of family role,
      outdoors, work/education, and social life. Implications for rehabilitation are
      included.

PMID- 29339859
TI  - Life Space Assessment in Spinal Cord Injury.
AB  - Objectives: To examine the Life Space Assessment (LSA) in persons with spinal
      cord injury (SCI), exploring its psychometric properties, differences between
      persons with cervical versus thoracolumbar injuries, and cutoff score
      differentiating a restricted from an unrestricted life space. Method: We
      conducted a test-retest reliability study in a community setting involving 50
      persons with SCI (25 injured above C7, 25 injured below T1). Data were collected
      in 2 phone interviews approximately 9 days apart using the LSA. Results: Mean LSA
      scores were 66 +/- 25 (n = 50): 62 +/- 23 for the cervical group, and 70 +/- 25
      for the thoracolumbar group. Scores were not significantly different between
      phone interviews [t(49) = 0.379, p = .706] or between groups [t(48) = -1.214, p =
      .231]. Test-retest reliability intraclass correlation coefficient (ICC) was 0.876
      (95% CI, 0.792-0.928). Spearman's rho correlations between the LSA and
      Reintegration to Normal Living Index total and subscores ranged from .509 to .538
      (p < .001). LSA scores were normally distributed. The minimum detectable change
      was approximately 23 points. A cutoff score of 78.5 (sensitivity 76.9%,
      specificity 81.1%) differentiated between persons with a restricted from an
      unrestricted life space if equipment and personal assistance were not needed for
      mobility. If equipment was needed, the cutoff score was found to be 49
      (sensitivity of 90%, specificity of 90%). Conclusions: The LSA is a reliable and
      valid measure of life space in persons with SCI and can be used to identify
      persons with a restricted life space who may be at increased risk of mobility
      disability.

PMID- 29339860
TI  - Early Access to Vocational Rehabilitation for Inpatients with Spinal Cord Injury:
      A Qualitative Study of Patients' Perceptions.
AB  - Background: A pilot early-intervention vocational rehabilitation program was
      conducted in Sydney, Australia, over a 2-year period. It was postulated that the
      early provision of integrated vocational rehabilitation services in the hospital
      settings for newly injured individuals would be well received and result in
      better employment and psychosocial health outcomes. Objective: The objective of
      this qualitative inquiry was to examine the perspectives of program participants
      who had completed the intervention about the timeliness, perceived value, and
      critical elements of the early intervention. Methods: A convenience sample of
      participants was selected by accessibility; participants were interviewed
      individually after discharge using a semi-structured approach. Transcripts of the
      interviews were created via audio recordings; interviews were transcribed
      verbatim, and the contents were analyzed thematically. Results: Thirteen
      participants aged from 19 to 60 years with varying levels of impairment and
      vocational backgrounds were interviewed from 7 to 21 months post injury. Overall,
      the early introduction of vocational rehabilitation services was well received
      and viewed positively. Emerging themes include sense of direction and
      distraction, advocacy, and support, with "hope" (early after injury) emerging as
      the overarching theme. Criticisms voiced about the program were that it was
      offered too early in the intensive care unit and there were competing interests
      and information overload in the early recovery phase. Conclusions: Vocational
      rehabilitation provided during inpatient rehabilitation appears appropriate,
      important, and valuable from patients' perspective. Early engagement results in
      feelings of hope and encourages patients to see the possibility of returning to
      work or education very early after injury, and it allows rehabilitation to be
      directed accordingly.

PMID- 29339861
TI  - Perceptions of Shared Decision Making Among Patients with Spinal Cord
      Injuries/Disorders.
AB  - Background: Individuals with spinal cord injuries/disorders (SCI/D) are
      interested in, and benefit from, shared decision making (SDM). Objective: To
      explore SDM among individuals with SCI/D and how demographics and health and
      SCI/D characteristics are related to SDM. Method: Individuals with SCI/D who were
      at least 1 year post injury, resided in the Chicago metropolitan area, and
      received SCI care at a Veterans Affairs (VA; n = 124) or an SCI Model Systems
      facility (n = 326) completed a mailed survey measuring demographics, health and
      SCI/D characteristics, physical and mental health status, and perceptions of
      care, including SDM, using the Combined Outcome Measure for Risk Communication
      and Treatment Decision-Making Effectiveness (COMRADE) that assesses decision
      making effectiveness (effectiveness) and risk communication (communication).
      Bivariate analyses and multiple linear regression were used to identify variables
      associated with SDM. Results: Participants were mostly male (83%) and White (70%)
      and were an average age of 54 years (SD = 14.3). Most had traumatic etiology, 44%
      paraplegia, and 49% complete injury. Veteran/civilian status and demographics
      were unrelated to scores. Bivariate analyses showed that individuals with
      tetraplegia had better effectiveness scores than those with paraplegia. Better
      effectiveness was correlated with better physical and mental health; better
      communication was correlated with better mental health. Multiple linear
      regressions showed that tetraplegia, better physical health, and better mental
      health were associated with better effectiveness, and better mental health was
      associated with better communication. Conclusion: SCI/D and health
      characteristics were the only variables associated with SDM. Interventions to
      increase engagement in SDM and provider attention to SDM may be beneficial,
      especially for individuals with paraplegia or in poorer physical and mental
      health.

PMID- 29339862
TI  - Posttraumatic Stress Symptoms Among Spinal Cord Injury Patients in Trauma: A
      Brief Report.
AB  - Background: Attention has recently focused on posttraumatic stress disorder
      (PTSD) among individuals with traumatic spinal cord injury (SCI). Purpose: To
      examine characteristics of individuals with and without symptoms of PTSD
      following acute SCI. Methods: Data were collected on 23 patients (age, 34.5 +/-
      14.4 years) at a Level I trauma center (14.35 +/- 18.48 days following injury).
      Results: There were 52.2% (n = 12) who experienced symptoms of PTSD post injury,
      with a significant association in patients with a history of psychological
      disorders (p = .0094). Conclusion: Findings suggest that patients with SCI who
      present with PTSD symptoms in the acute trauma care settting should be provided
      with specific cognitive behavioral interventions.

PMID- 29339864
TI  - Current Management Strategies of Hydrocephalus in the Child With Open Spina
      Bifida.
AB  - Symptomatic hydrocephalus is a common condition associated with myelomeningocele
      (open spina bifida). Traditionally, hydrocephalus was treated with insertion of a
      ventriculo-peritoneal (VP) shunt. This has been the standard of treatment since
      the introduction of the Holter shunt valve for the VP shunt in the late 1950s.
      Now there are other treatments that offer alternatives to VP shunt diversion for
      hydrocephalus. This article is a review of hydrocephalus associated with
      myelomeningocele and its treatment options. Treatment in the form of a VP shunt,
      endoscopic third ventriculostomy (ETV), and conservative management are
      discussed.

PMID- 29339865
TI  - Response of Scoliosis in Children with Myelomeningocele to Surgical Release of
      Tethered Spinal Cord.
AB  - Objective: To examine the effect of surgical tethered cord release (TCR) on
      scoliosis in children with myelomeningocele. Methods: A retrospective review of
      65 pediatric patients with myelomeningocele and TCR. The final sample consisted
      of 20 patients with scoliosis who were managed conservatively after TCR. Results:
      Average age at TCR was 6.2 years with average follow-up of 3.8 years. Scoliosis
      of 1 (5%) patient improved, 7 (35%) were stable, and 12 (60%) worsened (>=10
      degrees ). Fifty percent of patients ultimately required definitive spinal
      surgery. TCR release delayed definitive spine surgery for an average of 3.2
      years. Sixty-four percent of patients with curves less than or equal to 45
      degrees  had progression of their curves compared to 50% with curves greater than
      45 degrees . For patients with curves less than or equal to 45 degrees , curves
      progressed in 80% of those younger than 10 years as compared to 25% of those
      older than 10 years. For patients with curves less than or equal to 45 degrees ,
      43% required definitive spine surgery as opposed to 83% with curves greater than
      45 degrees . Level of neurological involvement (ie, lumbar versus thoracic) and
      age at untethering emerged as factors influencing the effects of TCR for patients
      with curves less than or equal to 45 degrees . Lumbar curves had more favorable
      results. Conclusion: Pediatric patients with myelomeningocele and scoliosis
      should be closely assessed and monitored. A selective approach for youth with
      lumbosacral level myelomeningocele and progressive curves less than or equal to
      45 degrees  may result in scoliosis stabilization and avoidance of definitive
      surgery.

PMID- 29339863
TI  - Prevention of Venous Thromboembolism in Individuals with Spinal Cord Injury:
      Clinical Practice Guidelines for Health Care Providers, 3rd ed.: Consortium for
      Spinal Cord Medicine.

PMID- 29339866
TI  - ADHD and Attention Problems in Children With and Without Spina Bifida.
AB  - Objectives: To identify differences in the diagnosis and treatment of attention
      deficit/hyperactivity disorder (ADHD) between typically developing children and
      children with spina bifida. Method: Sixty-eight children with spina bifida and 68
      demographically matched, typically developing children participated in a larger,
      longitudinal study. Rates of maternal, paternal, and teacher reports of attention
      problems, as well as rates of maternal reports of ADHD diagnosis, diagnosing
      provider, pharmaceutical treatment, mental health treatment, and academic
      accommodations were obtained at 5 time points over a period of 8 years and were
      compared across groups. Results: Children with spina bifida were more likely to
      have an ADHD diagnosis and attention problems. Attention problems and ADHD
      diagnoses were first reported at earlier time points for children with spina
      bifida than typically developing children. Among children with ADHD or attention
      problems, children with spina bifida were more likely to be treated with
      medication, but they were just as likely to use mental health services and
      receive resource services at school. Conclusions: Children with spina bifida were
      diagnosed with ADHD and identified as having attention problems more frequently
      and at an earlier age. This finding could be due to earlier symptom development,
      greater parental awareness, or more contact with providers. Among those with ADHD
      or attention problems, stimulant medication was more likely to be prescribed to
      children with spina bifida, despite research that suggests it may not be as
      beneficial for them. Further research on the effectiveness of ADHD
      pharmacological treatment for children with spina bifida is recommended.

PMID- 29339867
TI  - Does the CDC Definition of Fever Accurately Predict Inflammation and Infection in
      Persons With SCI?
AB  - Background: Pneumonia and septicemia have the greatest impact on reduced life
      expectancy in persons with spinal cord injury (SCI). Fever is often the first
      presenting symptom of infection or inflammation. Thermoregulatory dysfunction in
      persons with SCI may preclude a typical febrile response to infection or
      inflammation and thus delay diagnostic workup. Objective: To determine the core
      temperature of persons with SCI in the setting of infection or inflammation and
      the frequency with which it meets criteria for the CDC definition of fever
      (>100.4 degrees F). Methods: Retrospective review of hospitalized SCI patients
      over 5 years with a diagnosis of infection or inflammation (DI), defined by serum
      leukocytosis. In this study, 458 persons with paraplegia (PP) and 483 persons
      with tetraplegia (TP) had 4,191 DI episodes. Aural temperatures (Tau) on the day
      of DI, 7 days prior, and 14 days afterwards were abstracted from medical records.
      Main outcome measures were average Tau at DI, frequency of temperatures >100.4
      degrees F at DI, and average baseline temperatures before and after DI. Results:
      Average Tau at DI was 98.2 degrees F (+/-1.5) and 98.2 degrees F (+/-1.4) in the
      TP and PP groups, respectively, with only 11.6% to 14% of DI resulting in Tau
      >100.4 degrees F. Baseline temperatures ranged from 97.9 degrees F (+/-0.7) to
      98.0 degrees F (+/-0.8). Conclusion: SCI persons with leukocytosis infrequently
      mount a fever as defined by the CDC, and baseline temperatures were subnormal
      (<98.6 degrees F). Thermoregulatory dysfunction likely accounts for these
      findings. Tau >100.4 degrees F is not a sensitive predictor of infection or
      inflammation in persons with SCI. Clinicians should be vigilant for alternative
      symptoms of infection and inflammation in these patients, so diagnostic workup is
      not delayed.

PMID- 29339868
TI  - Feasibility and Acceptability of Implementing Indirect Calorimetry Into Routine
      Clinical Care of Patients With Spinal Cord Injury.
AB  - Background: In the absence of reliable predictive equations, indirect calorimetry
      (IC) remains the gold standard for assessing energy requirements after spinal
      cord injury (SCI), but it is typically confined to a research setting. The
      purpose of this study is to assess the feasibility and acceptability of
      implementing IC into routine clinical care in an Australian SCI rehabilitation
      facility. Methods: Bedside IC (canopy hood) was performed, and patients completed
      an IC acceptability questionnaire (open-ended; yes/no; 5-point Likert scale).
      Fasted resting energy expenditure (REE) steady-state criteria were applied to
      assess data quality, and adherence to a test >=20 minutes was recorded. Staff
      were surveyed to assess impact of IC on usual care. Results: Of 35 eligible
      patients, 9 declined (7 reported claustrophobia). One patient could not be tested
      before discharge and 25 underwent IC (84% male, injury level C2-L2, AIS A-D).
      Anxiety prevented one patient from completing IC, while another failed to fast.
      The remaining 23 patients achieved a steady-state REE (>=5 consecutive minutes
      with <=10% coefficient of variation for VO2 and VCO2). Test-retest (n = 5) showed
      <10% variation in REE. Patients deemed the procedure acceptable, with 88%
      reporting a willingness to repeat IC. Eighty percent of patients and 90% of staff
      agreed it was acceptable for IC to be integrated into usual care. Conclusion:
      This study found that IC is a feasible and acceptable addition to the routine
      clinical care of patients recovering from SCI and may serve to improve accuracy
      of nutrition interventions for this patient population.

PMID- 29339869
TI  - Developing a Model of Care for Healing Pressure Ulcers With Electrical
      Stimulation Therapy for Persons With Spinal Cord Injury.
AB  - Background: Electrical stimulation therapy (EST) has been shown to be an
      effective therapy for managing pressure ulcers in individuals with spinal cord
      injury (SCI). However, there is a lack of uptake of this therapy, and it is often
      not considered as a first-line treatment, particularly in the community.
      Objective: To develop a pressure ulcer model of care that is adapted to the local
      context by understanding the perceived barriers and facilitators to implementing
      EST, and to describe key initial phases of the implementation process. Method:
      Guided by the Knowledge-to-Action (KTA) and National Implementation Research
      Network (NIRN) frameworks, a community-based participatory research (CBPR)
      approach was used to complete key initial implementation processes including (a)
      defining the practice, (b) identifying the barriers and facilitators to EST
      implementation and organizing them into implementation drivers, and (c)
      developing a model of care that is adapted to the local environment. Results: A
      model of care for healing pressure ulcers with EST was developed for the local
      environment while taking into account key implementation barriers including lack
      of interdisciplinary collaboration and communication amongst providers between
      and across settings, inadequate training and education, and lack of resources,
      such as funding, time, and staff. Conclusions: Using established implementation
      science frameworks with structured planning and engaging local stakeholders are
      important exploratory steps to achieve a successful sustainable best practice
      implementation project.

PMID- 29339870
TI  - The Spinal Cord Outcomes Partnership Endeavor (SCOPE) SCI Clinical Trials Tables.

PMID- 29339871
TI  - Foreword.

PMID- 29339872
TI  - Neural Control and Physiology of Sexual Function: Effect of Spinal Cord Injury.
AB  - Objective: To present the current understanding of normal anatomy, physiology,
      sexual physiology, pathophysiology and the consequential sexual changes and
      dysfunctions following a spinal cord injury (SCI). Methods: Narrative review of
      the latest literature. Results: Peripheral innervations of the pelvis involve 3
      sets of efferent neurons coordinated though the pelvic plexus (somatic,
      thoracolumbar sympathetic, and sacral parasympathetic), and these are under
      cerebral descending excitatory and inhibitory control. SCI, depending on the
      level of lesion and completeness, can alter this cerebral control, affecting the
      psychological and reflexogenic potential for genital arousal and also ejaculation
      and orgasm. During arousal, nitric oxide is the main neurotransmitter for smooth
      muscle relaxation in both male and female erectile tissue. In men, erection,
      ejaculation, and orgasm are under separate neurological control and can be
      individually affected by SCI. Conclusions: Since sexual function is rated amongst
      the highest priorities by individuals living with SCI, methods employed to affect
      the neurological changes to maximize sexual neurophysiology prior to initiating
      medical therapies including paying attention to sexual sensate areas and visceral
      signals with mindfulness techniques, practicing body mapping, and sexual
      stimulation of sensate areas to encourage neuroplasticity. Attention should be
      paid to the biopsychosocial sexual contexts within which persons with SCI live to
      maximize their sexual and fertility rehabilitation.

PMID- 29339873
TI  - Cardiovascular Physiology and Responses to Sexual Activity in Individuals Living
      with Spinal Cord Injury.
AB  - Background: Spinal cord injury (SCI) may profoundly impact autonomic function
      producing a variable degree of dysfunction in cardiovascular, bronchopulmonary,
      sweating, bladder, bowel, and sexual function. The cardiovascular system is
      crucially important for sexual function, as it is responsible for blood flow
      shifts to cavernous and musculoskeletal tissue during sexual activity. This
      system is prone to 3 main abnormalities after SCI including low resting blood
      pressure (LRBP), orthostatic hypotension (OH), and autonomic dysreflexia (AD),
      all of which have important effects on sexual function. Methods: We review the
      current etiological mechanisms and manifestations of cardiovascular dysfunction
      after SCI and discuss how this is documented to impact sexual function in
      individuals living with SCI. Conclusions: All individuals with SCI at or above
      the T6 neurologic level have an increased risk of AD during sexual stimulation,
      with increasing risk associated with higher levels of injury and greater
      completeness of injury. AD can be silent, and individuals living with SCI should
      be aware of blood pressure values at baseline and during sexual activity.
      Clinicians performing vibrostimulation fertility procedures need to be aware of
      the risk of AD and consider pretreatment if needed. Researchers studying the
      cardiovascular response to sexual stimulation should consider continuous
      monitoring of blood pressure, as intermittent monitoring may underestimate true
      blood pressure values.

PMID- 29339874
TI  - Women's Sexual Health and Reproductive Function After SCI.
AB  - Sexual function and to a lesser extent reproduction are often disrupted in women
      with spinal cord injuries (SCI), who must be educated to better understand their
      sexual and reproductive health. Women with SCI are sexually active; they can use
      psychogenic or reflexogenic stimulation to obtain sexual pleasure and orgasm.
      Treatment should consider a holistic approach using autonomic standards to
      describe remaining sexual function and to assess both genital function and
      psychosocial factors. Assessment of genital function should include thoracolumbar
      dermatomes, vulvar sensitivity (touch, pressure, vibration), and sacral reflexes.
      Self-exploration should include not only clitoral stimulation, but also
      stimulation of the vagina (G spot), cervix, and nipples conveyed by different
      innervation sources. Treatments may consider PDE5 inhibitors and flibanserin on
      an individual basis, and secondary consequences of SCI should address concerns
      with spasticity, pain, incontinence, and side effects of medications.
      Psychosocial issues must be addressed as possible contributors to sexual
      dysfunctions (eg, lower self-esteem, past sexual history, depression, dating
      habits). Pregnancy is possible for women with SCI; younger age at the time of
      injury and at the time of pregnancy being significant predictors of successful
      pregnancy, along with marital status, motor score, mobility, and occupational
      scores. Pregnancy may decrease the level of functioning (eg, self-care,
      ambulation, upper-extremity tasks), may involve complications (eg, decubitus
      ulcers, weight gain, urological complications), and must be monitored for
      postural hypotension and autonomic dysreflexia. Taking into consideration the
      physical and psychosocial determinants of sexuality and childbearing allows women
      with SCI to achieve positive sexual and reproductive health.

PMID- 29339875
TI  - Reproductive Health of Men with Spinal Cord Injury.
AB  - Most men with spinal cord injury (SCI) are infertile due to a combination of
      erectile dysfunction, ejaculatory dysfunction, and abnormal semen quality. This
      article addresses issues that should be considered when managing the reproductive
      health of men with SCI. The authors present recommendations based on their
      decades of experience in managing the reproductive health of more than 1,000 men
      with SCI. Men with SCI face obstacles when pursuing sexual activity and/or
      biologic fatherhood. Hypogonadism and premature symptoms of aging may interfere
      with sexual function. Erectile dysfunction is prevalent in the SCI population,
      and treatments for erectile dysfunction in the general population are also
      effective in the SCI population. Most men with SCI cannot ejaculate with sexual
      intercourse. The procedures of penile vibratory stimulation (PVS) and/or
      electroejaculation (EEJ) are effective in obtaining an ejaculate from 97% of men
      with SCI. The ejaculate often contains sufficient total motile sperm to consider
      the assisted conception procedures of intrauterine insemination or even
      intravaginal insemination at home. If PVS and/or EEJ fail, sperm may be retrieved
      surgically from the testis or epididymis. Surgical sperm retrieval typically
      yields enough motile sperm only for in vitro fertilization with intracytoplasmic
      sperm injection. The majority of new cases of SCI occur in young men at the peak
      of their reproductive health. With proper medical management, these men can
      expect to experience active sexual lives and biologic fatherhood, if these are
      their goals. Numerous tools are available to physicians for helping these
      patients reach their goals.

PMID- 29339876
TI  - Sexuality in Pediatric Spinal Cord Injury.
AB  - Sexual development and sexuality in youth with pediatric spinal cord injury (SCI)
      are critical areas clinicians must be aware of and discuss when working with
      youth and their families. In addition to the general sexuality issues and
      challenges of adolescence and adult development, youth with SCI face unique
      physical and psychosocial issues. The goal of this article is to provide a
      developmentally based discussion of sexuality in individuals with SCI from
      infancy through emerging adulthood. An overview of psychosocial issues related to
      sexual development and sexuality are presented for each stage of sexual
      development along with recommendations for clinical practice, including patient
      and caregiver education and counseling. In order to establish expectations for
      youth with SCI, long-term outcomes related to sexuality and fertility of adults
      with pediatric-onset SCI are presented.

PMID- 29339877
TI  - A Multidisciplinary Approach to Sexual and Fertility Rehabilitation: The Sexual
      Rehabilitation Framework.
AB  - Many studies have identified improvement in sexual function as a priority for
      persons with spinal cord injury (SCI). Due to the various secondary sensory,
      motor, and autonomic consequences following SCI and due to the complexity of
      sexuality per se, this area can be overwhelming to many health care
      professionals. The literature indicate that sexual and fertility rehabilitation
      must be addressed in a biopsychosocial manner and include various disciplines.
      The multidisciplinary utilization of a Sexual Rehabilitation Framework (SRF)
      allows the medical and/or psychosocial factors that impede or improve sexual and
      reproductive function to be examined. The SRF is a user-friendly and simplified
      way to proactively address the major biopsychosocial areas of sexuality and to
      create a plan of action for the person with SCI. It is an adjunct tool to the
      full sexual history, and it encourages all disciplines involved in SCI
      rehabilitation to address the issue of sexual function in the same manner as they
      would other activities of daily living. Eight areas are included in the SRF:
      sexual drive/interest, sexual functioning, fertility and contraception, factors
      associated with the condition, motor and sensory influences, bladder and bowel
      influences, sexual self-view and self-esteem, and partnership issues. The use of
      the SRF is encouraged in both inpatient and outpatient settings.
      Multidisciplinary or interdisciplinary team work is encouraged in sexual and
      fertility rehabilitation to move clinicians toward providing proactive and
      comprehensive care for individuals with SCI or other chronic disabilities.

PMID- 29339878
TI  - Improving Sexual Satisfaction in Persons with Spinal Cord Injuries: Collective
      Wisdom.
AB  - Sexuality is an important part of life, and it is necessary for clinicians to
      have a specific format in which to address sexual issues with their patients. A
      systematic approach to working with patients with spinal cord injury (SCI) to
      improve their sexual functioning and response is presented. Nonjudgmental
      communication about sexual concerns is followed by a detailed pre- and postinjury
      medical, psychosocial, and sexual history. If preexisting sexual issues are
      present, it is recommended that the patient be referred for assessment and
      treatment of these separate from the patient's SCI-related concerns. Physical
      examination, with special attention to issues that could impact the patient's
      sexuality, is followed by a detailed neurologic assessment with specific
      attention to the T11-L2 and S3-5 spinal segments. Education of the patient with
      regard to his or her sexual potential and the need to be flexible in his or her
      sexual repertoire is followed by self-exploration and practice. Routine follow-up
      is suggested after patient's initial sexual exploration. Treatment of confounding
      and iatrogenic factors related to SCI is followed by more sexual experience.
      Afterwards the clinician is encouraged to use simple techniques to treat sexual
      issues and follow-up with the patient to assess the outcome. A structured program
      utilizing vibratory stimulation with or without midodrine is described as a way
      to achieve ejaculation and potentially orgasm, and techniques for treating severe
      autonomic dysreflexia are discussed. If these interventions do not alleviate the
      patient's sexual concerns, the clinician should refer the patient for more
      specialized consultation.

PMID- 29339879
TI  - How Do Iranian People with Spinal Cord Injury Understand Marriage?
AB  - Background: Spinal cord injury (SCI) is a life-altering experience. There is
      little information about the perspectives of people with SCI toward marriage.
      Purpose: To explore the understandings of Iranian adults with SCI about marriage.
      Methods: In this qualitative inquiry, using a semi-structured interview guide, we
      collected data from 53 single adults with SCI (41 men and 12 women) who were
      referred to the Brain and Spinal Cord Injury Research Center, Tehran University
      of Medical Sciences in Tehran. Barun and Clarke's thematic analysis approach was
      applied for data analysis. Results: "Marriage" was thematized in outer and inner
      scenarios. The outer scenario was explored in terms of physical disability
      identified as a seminal determinant in successful marriage. "Attractiveness,"
      "able body for breadwinning," "sexually active," and "reproduction" were dominant
      concepts extracted from the participants' narratives. The participants' inner
      scenarios revealed that marriage would be welcomed if a potential partner
      accepted them as a "whole person" regardless of their SCI condition. Conclusion:
      The findings suggest that adults with SCI do not ignore or reject marriage,
      however it was not their life priority due to major concerns that they had
      internalized. Considering the quality of care, people with SCI must be reassured
      about their potential to get married. SCI-based sexuality education and
      premarital counseling support the patients in their postmarital lives. Our
      findings will provide decision makers and health providers with significant
      insight for utilizing culturally appropriate services for people with SCI.

PMID- 29339881
TI  - Erratum.
AB  - [This corrects the article on p. 247 in vol. 22.].

PMID- 29339880
TI  - Description of Urological Surveillance and Urologic Ultrasonography Outcomes in a
      Cohort of Individuals with Long-Term Spinal Cord Injury.
AB  - Background: Individuals with spinal cord injury (SCI) have an increased risk of
      developing urological complications. Therefore, long-term routine urological
      surveillance is recommended. Objective: To describe urological surveillance in
      individuals with long-term SCI and to determine factors associated with urologic
      ultrasonography (UU) outcome. Methods: Wheelchair-dependent individuals with an
      SCI for 10 years or more were included. A medical assessment was done in 8
      participating rehabilitation centers. The International Lower Urinary Tract
      Function Basic SCI Data Set was used to assess bladder-emptying methods and
      previous surgical procedures on the urinary tract. We studied urological
      surveillance: whether participants had routine urological checkups (including UU)
      and when latest urodynamic study was performed. Latest UU (performed <1 year ago)
      was retrieved or, when lacking, UU was performed as part of our study. Results:
      Median time since injury (TSI) was 22.0 years. Overall, 39% of the 282
      participants did not have routine urological checkups and 33% never had a
      urodynamic study performed. UU data (N = 243) revealed dilatation of the upper
      urinary tract (UUT) in 4.5% of the participants and urinary stones in 5.7%.
      Abnormal UU outcome was associated with increasing TSI, nontraumatic SCI, and
      previous surgical bladder or UUT stone removal. UU outcome was not associated
      with routine urological checkups or type of bladder-emptying method. Conclusions:
      Over one-third of Dutch individuals with long-term SCI did not receive routine
      urological surveillance. UU outcome was not associated with routine urological
      checkups or type of bladder-emptying method. Further research on the indication
      and frequency of urological surveillance is recommended.

PMID- 29339882
TI  - Foreword.

PMID- 29339885
TI  - Consumer Feedback to Steer the Future of Assistive Technology Research and
      Development: A Pilot Study.
AB  - Objective: The overall objective of this project was to identify consumers'
      opinions of their needs and wants related to assistive technology (AT) in a
      systematic and quantitative manner via a questionnaire that can be used to
      validate existing and establish new research priorities. Methods: This pilot
      study describes questionnaire development, online implementation, and revisions
      considered to the questionnaire in preparation for conducting a nationwide
      survey. Data from a sample (N = 112) are presented. The pilot study was critical
      to refine the questions and ensure that meaningful information was being
      collected. Results: It was identified that revisions were warranted to provide
      more structure and allow for consumers to prioritize AT research efforts.
      Conclusion: The questionnaire results, although positively in favor of many of
      the technologies presented, are inconclusive to identify generalizable research
      priorities, thus expansion to a nationwide population is warranted.

PMID- 29339886
TI  - Step-Climbing Power Wheelchairs: A Literature Review.
AB  - Background: Power wheelchairs capable of overcoming environmental barriers, such
      as uneven terrain, curbs, or stairs, have been under development for more than a
      decade. Method: We conducted a systematic review of the scientific and
      engineering literature to identify these devices, and we provide brief
      descriptions of the mechanism and method of operation for each. We also present
      data comparing their capabilities in terms of step climbing and standard
      wheelchair functions. Results: We found that all the devices presented allow for
      traversal of obstacles that cannot be accomplished with traditional power
      wheelchairs, but the slow speeds and small wheel diameters of some designs make
      them only moderately effective in the basic area of efficient transport over
      level ground and the size and configuration of some others limit maneuverability
      in tight spaces. Conclusion: We propose that safety and performance test methods
      more comprehensive than the International Organization for Standards (ISO)
      testing protocols be developed for measuring the capabilities of advanced
      wheelchairs with step-climbing and other environment-negotiating features to
      allow comparison of their clinical effectiveness.

PMID- 29339887
TI  - Kinematics and Stability Analysis of a Novel Power Wheelchair When Traversing
      Architectural Barriers.
AB  - Background: Electric-powered wheelchairs (EPWs) are essential devices for people
      with disabilities for mobility and quality of life. However, the design of common
      EPWs makes it challenging for users to overcome architectural barriers, such as
      curbs and steep ramps. Current EPWs lack stability, which may lead to tipping the
      EPW causing injury to the user. An alternative Mobility Enhancement Robotic
      Wheelchair (MEBot), designed at the Human Engineering Research Laboratories
      (HERL), was designed to improve the mobility of, and accessibility for, EPW users
      in a wide variety of indoor and outdoor environments. Seat height and seat
      inclination can be adjusted using pneumatic actuators connected to MEBot's 6
      wheels. Method: This article discusses the design and development of MEBot,
      including its kinematics, stability margin, and calculation of the center of mass
      location when performing its mobility applications of curb climbing/descending
      and attitude control. Motion capture cameras recorded the seat angle and joint
      motion of the 6 wheel arms during the curb climbing/descending process. The
      center of mass location was recorded over a force plate for different footprint
      configurations. Results: Results showed that the area of the footprint changed
      with the location of the wheels during the curb climbing/descending and attitude
      control applications. The location of the center of mass moved +/-30 mm when the
      user leaned sideways, and the seat roll and pitch angle were 0 degrees  and +/
      4.0 degrees , respectively, during curb climbing and descending. Conclusion:
      Despite the user movement and seat angle change, MEBot maintained its stability
      as the center of mass remained over the wheelchair footprint when performing its
      mobility applications.

PMID- 29339888
TI  - Integration of Pneumatic Technology in Powered Mobility Devices.
AB  - Advances in electric motors, electronics, and control systems have enhanced the
      capability and drivability of electric power mobility devices over the last 60
      years. Yet, battery technologies used in powered mobility devices (PMDs) have not
      kept pace. Recent advances in pneumatic technology, primarily the high torque,
      low speed design of rotary piston air motors, directly align with the needs of
      PMD. Pneumatic technology has advantages over battery-powered technology,
      including lighter weight, lower operating costs, decreased environmental impact,
      better reliability, and increased safety. Two prototypes were created that
      incorporated rotary piston air motors, high-pressure air tanks, and air-pressure
      regulators. Prototype 1 was created by modifying an existing electric PMD. Range
      tests were performed to determine the feasibility of pneumatic technology and the
      optimal combination of components to allow the longest range possible at
      acceptable speeds over ideal conditions. Using a 1.44 L air tank for feasibility
      testing, prototype 1 was capable of traveling 800 m, which confirmed the
      feasibility of pneumatic technology usage in PMDs. Prototype 2 was designed based
      on the testing results from prototype 1. After further optimization of prototype
      2, the average maximum range was 3,150 m. Prototype 2 is up to 28.3% lighter than
      an equivalent size electric PMD and can be fully recharged in approximately 2
      minutes. It decreases the cost of PMDs by approximately $1,500, because batteries
      do not need to be replaced over the lifetime of the device. The results provide
      justification for the use of pneumatic technology in PMDs.

PMID- 29339889
TI  - Performance Evaluation of a Mobile Touchscreen Interface for Assistive Robotic
      Manipulators: A Pilot Study.
AB  - Background: Assistive robotic manipulators (ARMs) have been developed to provide
      enhanced assistance and independence in performance of daily activities among
      people with spinal cord injury when a caregiver is not on site. However, the
      current commercial ARM user interfaces (UIs) may be difficult to learn and
      control. A touchscreen mobile UI was developed to overcome these challenges.
      Objective: The object of this study was to evaluate the performance between 2 ARM
      UIs, touchscreen and the original joystick, using an ARM evaluation tool (ARMET).
      Methods: This is a pilot study of people with upper extremity impairments (N =
      8). Participants were trained on 2 UIs, and then they chose one to use when
      performing 3 tasks on the ARMET: flipping a toggle switch, pushing down a door
      handle, and turning a knob. Task completion time, mean velocity, and open
      interviews were the main outcome measurements. Results: Among 8 novice
      participants, 7 chose the touchscreen UI and 1 chose the joystick UI. All
      participants could complete the ARMET tasks independently. Use of the touchscreen
      UI resulted in enhanced ARMET performance (higher mean moving speed and faster
      task completion). Conclusions: Mobile ARM UIs demonstrated easier learning
      experience, less physical effort, and better ARMET performance. The improved
      performance, the accessibility, and lower physical effort suggested that the
      touchscreen UI might be an efficient tool for the ARM users.

PMID- 29339890
TI  - Further Development of a Robotic-Assisted Transfer Device.
AB  - Background: The task of performing transfers, such as from a wheelchair to a bed,
      has a high risk of injury to both the caregiver and the person being transferred.
      Although mechanical transfer devices can reduce these risks, these devices are
      not meant for use in the community and they still place strain on the caregiver
      when used. Purpose: The aim of this study is to describe feedback gathered from
      focus groups of potential users of the Robotic-Assisted Transfer Device (RATD)
      and describe design changes aimed at preparing the device for the next step in
      the development process. Method: The RATD was transferred to a newer electric
      powered wheelchair (EPW), key components were redesigned, and the control program
      was updated to increase the safety of the device. Two focus groups, one
      consisting of people with disabilities and the other consisting of clinicians and
      caregivers, were conducted to gather feedback from potential users. Results:
      Error checking, safety zones, a motor brake, and a new track helped increase the
      safety of the device. Sixty-three percent of the people with disabilities and 83%
      of caregivers surveyed said they would use the device. Conclusions: The results
      from the focus groups were positive and the design changes were successful, but
      more development is needed before the RATD can be marketed.

PMID- 29339891
TI  - Effect of Orthotic Gait Training with Isocentric Reciprocating Gait Orthosis on
      Walking in Children with Myelomeningocele.
AB  - Background: Mechanical orthoses are used to assist in standing and walking after
      neurological injury in children with myelomeningocele (MMC). Objectives: To
      evaluate the influence of orthotic gait training with an isocentric reciprocating
      gait orthosis (IRGO) on the kinematics and temporal-spatial parameters of walking
      in children with MMC. Methods: Five children with MMC were fitted with an IRGO.
      They walked at their own comfortable cadence using the orthosis. The hip joint
      angle, spatial temporal parameters, and compensatory motions were measured and
      analyzed. Results: Significant increases in walking speed and step length were
      demonstrated following orthotic gait training during walking with the IRGO. The
      sagittal plane hip range of motion was also significantly increased; however, the
      vertical and horizontal compensatory motions were significantly decreased.
      Conclusion: This study evaluated the influence of gait training with an IRGO on
      the kinematics and temporal spatial parameters in MMC children. The findings
      showed that orthotic gait training improved hip joint range of motion, increased
      walking speed and step length, and decreased lateral and vertical compensatory
      motions during level-ground walking trials.

PMID- 29339892
TI  - Care for Adults with Spina Bifida: Current State and Future Directions.
AB  - The care for adults with spina bifida is an important area to study. As
      increasing numbers of patients with spina bifida survive into adulthood, they
      expect to thrive and receive the best possible care into adulthood to maintain
      their health. Understanding the health needs in this emerging and changing
      population will help clinicians provide the best anticipatory care for adults
      with spina bifida and continue to improve outcomes. This will also impact
      pediatric care by improving the ability to determine preventive methods from
      early on and understand the impacts of pediatric care and decisions over the
      lifespan.

PMID- 29339893
TI  - Shoulder Functional Electrical Stimulation During Wheelchair Propulsion in Spinal
      Cord Injury Subjects.
AB  - Background: Subjects with spinal cord injury (SCI) propel their wheelchairs by
      generating a different level of muscle activity given their multiple deficits in
      muscle strength. Exercise training programs seem to be effective in improving
      wheelchair propulsion capacity. Functional electrical stimulation (FES) therapy
      is a complementary tool for rehabilitation programs. Objectives: To determine the
      accuracy of the synchronization between the FES activation and the push phase of
      the propulsion cycle by using hand pressure sensors that allow anterior deltoids
      activation when the hand is in contact with the pushrim. Methods: We analyzed 2
      subjects, with injuries at C6 American Spinal Injury Association Impairment Scale
      (AIS) A and T12 AIS A. The stimulation parameters were set for a 30 Hz frequency
      symmetrical biphasic wave, 300 MUs pulse width. Data were collected as
      participants propelled the wheelchair over a 10-m section of smooth, level vinyl
      floor. Subjects were evaluated in a motion analysis laboratory (ELITE; BTS,
      Milan, Italy). Results: Subject 1 showed synchronization between the FES
      activation and the push phase of 87.5% in the left hand and of 80% in the right
      hand. Subject 2 showed synchronization of 95.1% in the left and of hand 94.9% in
      the right hand. Conclusion: Our study determined a high accuracy of a novel FES
      therapeutic option, showing the synchronization between the electrical
      stimulation and the push phase of the propulsion cycle.

PMID- 29339894
TI  - Exercise and Health-Related Risks of Physical Deconditioning After Spinal Cord
      Injury.
AB  - A sedentary lifestyle occurring soon after spinal cord injury (SCI) may be in
      contrast to a preinjury history of active physical engagement and is thereafter
      associated with profound physical deconditioning sustained throughout the
      lifespan. This physical deconditioning contributes in varying degrees to lifelong
      medical complications, including accelerated cardiovascular disease, insulin
      resistance, osteopenia, and visceral obesity. Unlike persons without disability
      for whom exercise is readily available and easily accomplished, exercise options
      for persons with SCI are more limited. Depending on the level of injury, the
      metabolic responses to acute exercise may also be less robust than those
      accompanying exercise in persons without disability, the training benefits more
      difficult to achieve, and the risks of ill-considered exercise both greater and
      potentially irreversible. For exercise to ultimately promote benefit and not
      impose additional impairment, an understanding of exercise opportunities and
      risks if exercise is undertaken by those with SCI is important. The following
      monograph will thus address common medical challenges experienced by persons with
      SCI and typical modes and benefits of voluntary exercise conditioning.

PMID- 29339897
TI  - Exploration of the Personal Health Record as a Tool for Spinal Cord Injury Health
      Self-Management and Coordination of Care.
AB  - Background: A personal health record (PHR) is a collection of electronic health
      data drawn from multiple sources but managed by the patient. The PHR is a
      strategy that enables patients to be proactive in the coordination of their care.
      Objective: The purpose of this clinical improvement study was to discover what
      worked, what did not work, and what could be improved in the initial
      implementation of MyPHR, a PHR tailored to patients with spinal cord injury
      (SCI), to make it a useful tool for care coordination and health self-management.
      Methods: Five individuals with chronic (>1 year) SCI carried out trial use of
      MyPHR. Twelve hours of interactions, including screen navigation and think-aloud
      reflection, were recorded and analyzed using formative research, a qualitative
      method and type of case study research. Results: Two key themes emerged to guide
      the implementation of PHR technology: selectivity in the identification of
      information for the patient to track, and continual support and communication
      with the clinical team. Conclusion: Given the volume of electronic data available
      to patients with SCI, the data identified to import, manage, and keep current in
      a PHR have to be thoughtfully selected to make sure the patient is convinced of
      the worth of this data record and is willing to invest the time and effort it
      will take to maintain it. A PHR should be implemented with a deliberate focus on
      its function as a tool that patients and providers use together to expand
      communication as they work toward their common goal of optimizing health after
      SCI.

PMID- 29339896
TI  - Inflammatory Stress Effects on Health and Function After Spinal Cord Injury.
AB  - Background: Injury to the spinal cord produces immediate, adaptive inflammatory
      responses that can exacerbate the initial injury and lead to secondary damage.
      Thus far, researchers and clinicians have focused on modulating acute
      inflammation to preserve sensorimotor function. However, this singular approach
      risks overlooking how chronic inflammation negatively impacts the broader health
      of persons with a spinal cord injury (SCI). Objective: The aim of this monograph
      was to discuss interrelated processes causing persistent inflammatory stress
      after SCI, along with associated health risks. We review archetypal factors that
      contribute to a chronic inflammatory state, including response to injury, acute
      infection, and autonomic dysreflexia. Secondary complications producing and
      exacerbating inflammation are also discussed, including pain, depression,
      obesity, and injury to the integumentary and skeletal systems. Finally, we
      discuss the role of bacteria and the gut microbiome in this process and then
      conclude with a discussion on how a pro-inflammatory phenotype promotes an
      elevated risk for cardiovascular disease after injury. Conclusions: Effectively
      managing chronic inflammation should be a high priority for clinicians and
      researchers who seek to improve the health and life quality of persons with SCI.
      Chronic inflammation worsens secondary medical complications and amplifies the
      risk for cardiometabolic disorders after injury, directly impacting both the
      quality of life and mortality risk after SCI. Inflammation can worsen pain and
      depression and even hinder neurological recovery. It is, therefore, imperative
      that countermeasures to chronic inflammation are routinely considered from the
      point of initial injury and proceeding throughout the lifespan of the individual
      with SCI.

PMID- 29339898
TI  - Overground Locomotor Training in Spinal Cord Injury: A Performance-Based
      Framework.
AB  - Background: Locomotor training (LT) is the most commonly used treatment to
      improve walking performance following spinal cord injury (SCI). The advancement
      of LT treatments requires the addition of integrative models accounting for the
      numerous systems responsible for the recovery of walking function following SCI.
      Objective: This perspective monograph aims to (a) describe a performance-based
      framework for overground LT (OLT), (b) describe principles of adaptation and
      motor learning used to inform OLT program design, and (c) present an example OLT
      program based on the proposed framework. Methods: Individuals with chronic motor
      incomplete SCI (7 male, 1 female) classified according to the American Spinal
      Injury Association Impairment Scale (AIS) as C and D were included. OLT included
      two 90-minute sessions performed over 12 weeks for a total of 24 sessions.
      Outcomes measures included overground walking speed, walking economy, pulmonary
      oxygen uptake, and muscle oxygen extraction measured via near-infrared
      spectroscopy. Results: Preliminary findings demonstrate the potential of OLT, as
      describe here, to increase overground walking speed, improve walking economy,
      accelerate processes associated with oxygen delivery and utilization at the rest
      to-work transition, and lower oxygen extraction requirements of skeletal muscle
      during walking in individuals with chronic motor-incomplete SCI. Conclusion: The
      proposed framework offers a valuable template for LT program design in both
      clinical and research settings. Further research is necessary to better
      understand the effects of OLT and how principles of specificity, progressive
      overload, and variation within the performance-based framework can be manipulated
      to maximize function, health, and quality of life in SCI.

PMID- 29339895
TI  - Nutritional Health Considerations for Persons with Spinal Cord Injury.
AB  - Chronic spinal cord injury (SCI) often results in morbidity and mortality due to
      all-cause cardiovascular disease (CVD) and comorbid endocrine disorders. Several
      component risk factors for CVD, described as the cardiometabolic syndrome (CMS),
      are prevalent in SCI, with the individual risks of obesity and insulin resistance
      known to advance the disease prognosis to a greater extent than other established
      risks. Notably, adiposity and insulin resistance are attributed in large part to
      a commonly observed maladaptive dietary/nutritional profile. Although there are
      no evidence-based nutritional guidelines to address the CMS risk in SCI,
      contemporary treatment strategies advocate more comprehensive lifestyle
      management that includes sustained nutritional guidance as a necessary component
      for overall health management. This monograph describes factors in SCI that
      contribute to CMS risks, the current nutritional profile and its contribution to
      CMS risks, and effective treatment strategies including the adaptability of the
      Diabetes Prevention Program (DPP) to SCI. Establishing appropriate nutritional
      guidelines and recommendations will play an important role in addressing the CMS
      risks in SCI and preserving optimal long-term health.

PMID- 29339899
TI  - Clinician-Focused Overview of Bionic Exoskeleton Use After Spinal Cord Injury.
AB  - Spinal cord injury (SCI) resulting in paralysis of lower limbs and trunk
      restricts daily upright activity, work capacity, and ambulation ability, putting
      persons with an injury at greater risk of developing a myriad of secondary
      medical issues. Time spent in the upright posture has been shown to decrease the
      risk of these complications in SCI. Unfortunately, the majority of ambulation
      assistive technologies are limited by inefficiencies such as high energy demand,
      lengthy donning and doffing time, and poor gait pattern precluding widespread
      use. These limitations spurred the development of bionic exoskeletons. These
      devices are currently being used in rehabilitation settings for gait retraining,
      and some have been approved for home use. This overview will address the current
      state of available devices and their utility.

PMID- 29339900
TI  - Exoskeleton Training May Improve Level of Physical Activity After Spinal Cord
      Injury: A Case Series.
AB  - Objectives: To determine whether the use of a powered exoskeleton can improve
      parameters of physical activity as determined by walking time, stand up time, and
      number of steps in persons with spinal cord injury (SCI). Methods: Three men with
      complete (1 C5 AIS A and 2 T4 AIS A) and one man with incomplete (C5 AIS D) SCI
      participated in a clinical rehabilitation program. In the training program, the
      participants walked once weekly using a powered exoskeleton (Ekso) for
      approximately 1 hour over the course of 10 to 15 weeks. Walking time, stand up
      time, ratio of walking to stand up time, and number of steps were determined.
      Oxygen uptake (L/min), energy expenditure, and body composition were measured in
      one participant after training. Results: Over the course of 10 to 15 weeks, the
      maximum walking time increased from 12 to 57 minutes and the number of steps
      increased from 59 to 2,284 steps. At the end of the training, the 4 participants
      were able to exercise for 26 to 59 minutes. For one participant, oxygen uptake
      increased from 0.27 L/min during rest to 0.55 L/min during walking. Maximum
      walking speed was 0.24 m/s, and delta energy expenditure increased by 1.4
      kcal/min during walking. Body composition showed a modest decrease in absolute
      fat mass in one participant. Conclusion: Exoskeleton training may improve
      parameters of physical activity after SCI by increasing the number of steps and
      walking time. Other benefits may include increasing energy expenditure and
      improving the profile of body composition.

PMID- 29339901
TI  - Influence of Reciprocating Link When Using an Isocentric Reciprocating Gait
      Orthosis (IRGO) on Walking in Patients with Spinal Cord Injury: A Pilot Study.
AB  - Background: Studies collectively imply that the reciprocal link has no effect on
      walking when using reciprocating gait orthoses (RGOs). There may be differences
      between the 2 configurations of the RGO (eg, isocentric reciprocating gait
      orthosis [IRGO] and IRGO without reciprocating link), but the specific benefits
      and problems encountered in their use must be understood. Purpose: To highlight
      more evidence for the mechanical function of the reciprocal link in RGOs used for
      walking by individuals with spinal cord injury (SCI). Methods: Nine people with
      SCI participated in this study. Gait analysis was performed in 2 conditions
      (walking with IRGO and walking with IRGO without reciprocating link) in a random
      order. The Vicon digital capture system was used to obtain kinematic data.
      Results: There were significant differences between each orthotic configuration
      in terms of speed of walking (p = .029), step length (p = .048), hip joint range
      of motion (ROM) (p <= .001), and lateral and vertical compensatory motions (p <=
      .001). There was no significant difference between each orthotic configuration in
      cadence (p = .162). Conclusion: The reciprocating link in IRGO improved the
      walking parameters in SCI patients.

PMID- 29339902
TI  - Study on the Effectiveness of Virtual Reality Game-Based Training on Balance and
      Functional Performance in Individuals with Paraplegia.
AB  - Objective: To determine whether there is any difference between virtual reality
      game-based balance training and real-world task-specific balance training in
      improving sitting balance and functional performance in individuals with
      paraplegia. Methods: The study was a pre test-post test experimental design.
      There were 30 participants (28 males, 2 females) with traumatic spinal cord
      injury randomly assigned to 2 groups (group A and B). The levels of spinal injury
      of the participants were between T6 and T12. The virtual reality game-based
      balance training and real-world task-specific balance training were used as
      interventions in groups A and B, respectively. The total duration of the
      intervention was 4 weeks, with a frequency of 5 times a week; each training
      session lasted 45 minutes. The outcome measures were modified Functional Reach
      Test (mFRT), t-shirt test, and the self-care component of the Spinal Cord
      Independence Measure-III (SCIM-III). Results: There was a significant difference
      for time (p = .001) and Time * Group effect (p = .001) in mFRT scores, group
      effect (p = .05) in t-shirt test scores, and time effect (p = .001) in the self
      care component of SCIM-III. Conclusions: Virtual reality game-based training is
      better in improving balance and functional performance in individuals with
      paraplegia than real-world task-specific balance training.

PMID- 29339903
TI  - Economic Consequences of an Implanted Neuroprosthesis in Subjects with Spinal
      Cord Injury for Restoration of an Effective Cough.
AB  - Objective: To determine if an implanted neuroprosthesis for restoration of an
      effective cough is less costly than conventional methods of respiratory
      management. Methods: Nonrandomized clinical trial of participants (N = 14) with
      spinal cord injury (SCI) using the Cough Stimulator device in the inpatient
      hospital setting for Cough Stimulator implantation and outpatient hospital or
      residence for follow-up. A neuroprosthesis was implanted for restoration of an
      effective cough. The annual costs associated with respiratory management, without
      (pre implantation) and with (post implantation) the neuroprosthesis, were
      examined over a 4-year period. Results: The total cost related to implantation of
      the Cough Stimulator was $59,891, with no maintenance costs over subsequent
      years. The incidence of respiratory tract infections and the need for caregiver
      support fell significantly following implantation. The costs associated with
      respiratory tract infections fell significantly from a mean of $36,406 +/-
      11,855/year to $13,284 +/- 7,035/year (p < .05) pre and post implantation,
      respectively. Costs fell further to $8,817 +/- 5,990 and $4,467 +/- 4,404
      following the 2nd and 3rd years post implantation (p < .05), respectively. The
      costs associated with caregiver support fell significantly from $25,312 +/-
      8,019/year to $2,630 +/- 2,233/year (p < .05) pre and post implantation,
      respectively, and remained low in subsequent years (p < .05). Other costs related
      to secretion management fell significantly and remained low in subsequent years
      (p < .05). Break-even analysis demonstrated that this point was reached in the
      first year. Conclusion: The results of this investigation demonstrate that
      implantation and use of the Cough Stimulator resulted in significant reductions
      in the overall costs of respiratory management in this patient population.

PMID- 29339904
TI  - Epidemiology of Pediatric Traumatic and Acquired Nontraumatic Spinal Cord Injury
      in Ireland.
AB  - Objective: To examine the epidemiology of pediatric traumatic (TSCI) and acquired
      nontraumatic spinal cord injury (NTSCI) in Ireland. There are few studies
      reporting pediatric TSCI incidence and fewer of pediatric NTSCI incidence,
      although there are several case reports. As there is a single specialist
      rehabilitation facility for these children, complete population-level data can be
      obtained. Method: Retrospective review of prospectively gathered data in the
      Patient Administration System of the National Rehabilitation Hospital of patients
      age 15 years or younger at the time of SCI onset. Information was retrieved on
      gender, age, etiology, level of injury/AIS. Population denominator was census
      results from 1996, 2002, 2006, and 2011, rolled forward. Results: Since 2000, 22
      children have sustained TSCI and 26 have sustained NTSCI. Median (IQR) age at
      TSCI onset was 6.3 (4.4) years, and at NTSCI onset it was 7.3 (8.1) years. Most
      common TSCI etiology was transportation (n = 10; 45.5%), followed by surgical
      complications (n = 8; 36.4%); most common injury type was complete paraplegia (n
      = 12; 54.5%) followed by incomplete paraplegia (n = 5; 22.7%). Most common NTSCI
      etiology was transverse myelitis (n = 11; 42.3%) followed by vascular (n = 5;
      20%); most common injury type was incomplete paraplegia (n = 17; 65.4%) followed
      by incomplete tetraplegia (n = 6; 24%). Incidence of TSCI ranged from 0 to 3.1
      per million per year; incidence of NTSCI ranged from 0 to 6.5 per million per
      year. Conclusion: Incidence of SCI in Ireland seems similar to or slightly lower
      than other developed countries. Injury patterns are also similar, considering
      variations in reporting methods.

PMID- 29339905
TI  - Review of the History of Non-traumatic Spinal Cord Dysfunction.
AB  - Background: The incidence of non-traumatic spinal cord dysfunction (SCDys) is
      reported to be higher than traumatic spinal cord injury (SCI) in many countries.
      No formal review of the history of SCDys has been published. Objective: This
      article aims to identify key highlights in the history of SCDys. Method: An
      electronic literature search was conducted (January 2017) using MEDLINE (1946
      2016) and Embase (1974-2016) databases for publications regarding the history of
      SCDys. Publications on the history of SCI and a selection of neurology textbooks
      and books on the history of neurology were reviewed for potentially relevant
      references. The focus of the literature search was on identifying publications
      that detail key highlights regarding the history of the diagnosis and management
      of the most common SCDys conditions, as well as those of historical significance.
      Results: The electronic search of MEDLINE and Embase identified 11 relevant
      publications. The majority of publications included were identified from the
      authors' libraries and a selection of books on neurology and the history of
      neurology. Conclusions: This review outlines the history of SCDys, taking a
      broader historical perspective and covering the increasing awareness of the role
      of the spinal cord and knowledge of neuroanatomy. Key milestones in the history
      of the diagnosis and management of the most common SCDys conditions are
      presented. An appreciation of the history of SCDys increases our understanding of
      the large number of people who contributed to our current knowledge of these
      conditions and in some situations helps guide efforts regarding prevention of
      SCDys.

PMID- 29339906
TI  - Important Clinical Rehabilitation Principles Unique to People with Non-traumatic
      Spinal Cord Dysfunction.
AB  - Background: Non-traumatic spinal cord dysfunction (SCDys) is caused by a large
      range of heterogeneous etiologies. Although most aspects of rehabilitation for
      traumatic spinal cord injury and SCDys are the same, people with SCDys have some
      unique rehabilitation issues. Purpose: This article presents an overview of
      important clinical rehabilitation principles unique to SCDys. Methods: Electronic
      literature search conducted (January 2017) using MEDLINE and Embase (1990-2016)
      databases for publications regarding SCDys. The focus of the literature search
      was on identifying publications that present suggestions regarding the clinical
      rehabilitation of SCDys. Results: The electronic search of MEDLINE and Embase
      identified no relevant publications, and the publications included were from the
      authors' libraries. A number of important clinical rehabilitation principles
      unique to people with SCDys were identified, including classification issues,
      general rehabilitation issues, etiology-specific issues, and a role for the
      rehabilitation physician as a diagnostic clinician. The classification issues
      were regarding the etiology of SCDys and the International Standards for
      Neurological Classification of Spinal Cord Injury. The general rehabilitation
      issues were predicting survival, improvement, and rehabilitation outcomes;
      admission to spinal rehabilitation units, including selection decision issues;
      participation in rehabilitation; and secondary health conditions. The etiology
      specific issues were for SCDys due to spinal cord degeneration, tumors, and
      infections. Conclusions: Although there are special considerations regarding the
      rehabilitation of people with SCDys, such as the potential for progression of the
      underlying condition, functional improvement is typically significant with
      adequate planning of rehabilitation programs and special attention regarding the
      clinical condition of patients with SCDys.

PMID- 29339907
TI  - Trends, Challenges, and Opportunities Regarding Research in Non-traumatic Spinal
      Cord Dysfunction.
AB  - Background: Spinal cord dysfunction (SCDys) is caused by heterogeneous health
      conditions, and the incidence is increasing. Despite the growing interest in
      rehabilitation research for SCDys, research into SCDys faces many challenges.
      Objective: The objective of this project was to perform a clinical review of
      changes in SCDys research over the last 4 decades; identify challenges to
      conducting research in SCDys; and propose opportunities for improving research in
      SCDys. Methods: A triangulation approach was used for obtaining evidence:
      literature search (January 2017) using MEDLINE and Embase databases for
      publications in English (1974-2016) regarding SCDys; workshop discussions at the
      International Spinal Cord Society annual meeting, September 16, 2016, Vienna,
      Austria; and our collective expertise in SCDys clinical rehabilitation research.
      Results: There has been a substantial increase in publications on SCDys over the
      4 decades, from 1,825 in 1974-1983 to 11,887 in the decade 2004-2013, along with
      an improvement in research methodology. Numerous challenges to research in SCDys
      rehabilitation were grouped into the following themes: (a) identification of
      cases; (b) study design and data collection; and (c) funding, preclinical, and
      international research. Opportunities for addressing these were identified.
      Conclusions: The increase in scientific publications on SCDys highlights the
      importance of this heterogeneous group among the research community. The overall
      lack of good quality epidemiological studies regarding incidence, prevalence, and
      survival in these patients serves as a benchmark for guiding improvements to
      inform evidence-based care and policy.

PMID- 29339908
TI  - Creation of an Algorithm to Identify Non-traumatic Spinal Cord Dysfunction
      Patients in Canada Using Administrative Health Data.
AB  - Background: The lack of consensus on the best methodology for identifying cases
      of non-traumatic spinal cord dysfunction (NTSCD) in administrative health data
      limits the ability to determine the burden of disease and provide evidence
      informed services. Objective: The purpose of this study is to develop an
      algorithm for identifying cases of NTSCD with Canadian health administrative
      databases using a case-based approach. Method: Data were provided by the Canadian
      Institute for Health Information that included all acute care hospital and day
      surgery (Discharge Abstract Database), ambulatory (National Ambulatory Care
      Reporting System), and inpatient rehabilitation records (National Rehabilitation
      Reporting System) of patients with neurological impairment (paraplegia,
      tetraplegia, and cauda equina syndrome) between April 1, 2004 and March 31, 2011.
      The approach to identify cases of NTSCD involved using a combination of
      diagnostic codes for neurological impairment and NTSCD etiology. Results: Of the
      initial cohort of 23,703 patients with neurological impairment, we classified
      6,362 as the "most likely NTSCD" group (had a most responsible diagnosis or pre
      existing diagnosis of NTSCD and diagnosis of neurological impairment); 2,777 as
      "probable NTSCD" defined as having a secondary diagnosis of NTSCD, and 11,179 as
      "possible NTSCD" who had no NTSCD etiology diagnoses but neurological impairment
      codes. Conclusion: The proposed algorithm identifies an inpatient NTSCD cohort
      that is limited to patients with significant paralysis. This feasibility study is
      the first in a series of 3 that has the potential to inform future research
      initiatives to accurately determine the incidence and prevalence of NTSCD.

PMID- 29339909
TI  - Validation of Algorithm to Identify Persons with Non-traumatic Spinal Cord
      Dysfunction in Canada Using Administrative Health Data.
AB  - Background: Administrative health data, such as the hospital Discharge Abstract
      Database (DAD), can potentially be used to identify patients with non-traumatic
      spinal cord dysfunction (NTSCD). Algorithms utilizing administrative health data
      for this purpose should be validated before clinical use. Objective: To validate
      an algorithm designed to identify patients with NTSCD through DAD. Method: DAD
      between 2006 and 2016 for Southern Alberta in Canada were obtained through
      Alberta Health Services. Cases of NTSCD were identified using the algorithm
      designed by the research team. These were then validated by chart review using
      electronic medical records where possible and paper records where electronic
      records were unavailable. Measures of diagnostic accuracy including sensitivity,
      specificity, and positive and negative predictive values and 95% confidence
      intervals (CI) were computed. Results: Two hundred and eighty cases were
      identified to have both the administrative codes for neurological impairments and
      NTSCD etiology. Twenty-eight cases were excluded from analysis as 5 had
      inadequate medical record information, 17 had traumatic spinal cord injury, and 6
      were considered "other" non-spinal cord conditions. Measures of diagnostic
      accuracy that were computed were sensitivity 97% (95% CI, 94%-98%), specificity
      60% (95% CI, 47%-73%), positive predictive value (PPV) 92% (95% CI, 88%-95%), and
      negative predictive value (NPV) 80% (95% CI, 65%-90%). The most prevalent
      etiologies were degenerative (36.9%), infection (19.0%), oncology malignant
      (15.1%), and vascular (10.3%). Conclusion: Our algorithm has high sensitivity and
      PPV and satisfactory specificity and NPV for the identification of persons with
      NTSCD using DAD, though the limitations for using this method should be
      recognized.

PMID- 29339910
TI  - Characteristics of Non-traumatic Spinal Cord Dysfunction in Canada Using
      Administrative Health Data.
AB  - Background: There is a paucity of studies using administrative health data to
      examine the epidemiology, health care utilization, and outcomes for non-traumatic
      spinal cord dysfunction (NTSCD). Objective: The purpose of this study is to
      characterize discrete NTSCD cohorts using decision algorithms with Canadian
      health administrative databases. Method: Data were provided by the Canadian
      Institute for Health Information that included all acute care hospital, day
      surgery, ambulatory, and inpatient rehabilitation records of patients with
      neurological impairment between April 1, 2004 and March 31, 2011. Diagnostic
      codes for neurological impairment and NTSCD etiology were used to identify cases
      and classify 3 NTSCD groups (most likely, probable, and possible). Logistic
      regression identified factors related to inpatient rehabilitation admission
      within 7 days of discharge among the preferred group. Results: The most likely
      NTSCD group (n = 6,362) was significantly older and had a greater proportion of
      women and individuals with cauda equina lesions compared to the other 2 NTSCD
      groups (probable [n = 2,777] and possible [n = 11,179]; ps < .001). Factors
      associated with the likelihood of an inpatient rehabilitation admission included
      being older (odds ratio [OR], 1.01; 95% CI, 1.00-1.01), being female (OR, 1.18;
      95% CI, 1.06-1.32), having paraplegia diagnosis compared to cauda equina (OR,
      1.24; 95% CI, 1.09-1.41), residing in an urban area compared to a rural area (OR,
      1.34; 95% CI, 1.13-1.58), having degenerative etiology compared to other (OR,
      1.59; 95% CI, 1.41-1.80), and having an MRI on record compared to not (OR = 1.57;
      95% CI, 1.39-1.76). Conclusion: Administrative data allow for ongoing
      surveillance of a population in a relatively cost-effective manner. Advancing our
      knowledge of NTSCD epidemiology, health outcomes, and system performance can
      inform policy and system planning.

PMID- 29339911
TI  - Nature of the Non-traumatic Spinal Cord Injury Literature: A Systematic Review.
AB  - Background: Non-traumatic SCI (NTSCI) etiologies represent a markedly
      heterogeneous cluster of conditions defined within the consensus NTSCI taxonomy.
      This meta-analysis assembles evidence about the occurrence of NTSCI and its
      clinical outcomes with respect to 6 research domains. Purpose: To investigate the
      quality and quantity of clinical NTSCI evidence published in the peer reviewed
      literature with reference to prognosis, diagnosis, intervention, process of care,
      methodology, and qualitative approaches. Methods: PubMed and MEDLINE OVID MeSH
      heading searches were conducted for 5 common-language NTSCI descriptors. Filters
      were English language and Entrez date (1997-2016). Filters also controlled for
      case reports, editorials or errata, and invited reviews. NTSCI etiologies
      incorrectly classified, animal studies, and multidimensional mapping studies were
      excluded. Full texts were retrieved and ranked for evidence quality according to
      PRISMA statement guidelines, or PEDro criteria. Data were extracted and simple
      descriptive statistics applied. Results: The search terms non traumatic and non
      traumatic SCI retrieved 282 articles, with 39 duplicates. After exclusion of 117
      articles: Level 1V (60); NTSCI incorrectly evaluated (14); publication bias (2);
      non-English language (1); and animal experiments (1), 126 titles/abstracts were
      screened and ranked against criteria. Of the 8 papers allocated for full-text
      review, a subset of 3 articles was ranked level 1A (1) or level 11A (2); mean
      PEDro score 5.75+/-0.5. Reasons for full-text exclusions (5) were NTSCI
      incorrectly classified (1) and statistical limitations (4). Of the 6 domains,
      prognostics had adequate data yield (86) for evidence synthesis (4.8% ranked
      level 1A, or 11A). Notable evidence gaps were identified in qualitative (1),
      methodological (2), and diagnostic (8) domains. Conclusion: Therapeutic
      approaches require an evidence-based understanding of the distinct contexts in
      which NTSCI occurs, especially in less resourced settings. Our findings
      underscore the need for qualitative and quantitative research on the occurrence
      of NTSCI in all contexts.

PMID- 29339912
TI  - Outcomes Following Ischemic Myelopathies and Traumatic Spinal Injury.
AB  - Background: As the general population ages, the rising prevalence of vascular
      lesions of the spinal cord will become significant. Purpose: The aim of this
      study was to compare the neurological and functional outcomes of patients with
      ischemic spinal cord injury (ISCI) and traumatic spinal cord injury (TSCI).
      Methods: We conducted a retrospective study in a spinal cord unit of 2
      rehabilitation hospitals. We studied 168 patients with a TSCI and 72 with an
      ISCI. At admission and discharge, patients were evaluated by American Spinal
      Injury Association Impairment Scale (AIS) standards and Spinal Cord Independence
      Measure (SCIM). Length of stay, occurrence of complications, and discharge
      dispositions were also recorded. Linear and logistic regression models were used
      to analyze the effects of the etiology of the lesion, AIS level at admission, and
      level of the lesion. Results: Patients with an ISCI were older and experienced
      fewer cervical lesions and fewer complete lesions than patients with TSCI. By
      linear and logistic regression, etiology was a predictor (together with lesion
      features) of functional (SCIM improvement and SCIM at discharge) outcome, with
      traumatic patients having better outcome than ischemic ones. Age, AIS level, and
      lesion level were the chief predictors of length of stay, occurrence of
      complications, and discharge dispositions. Conclusions: A diagnosis of ischemia
      and trauma could be a determinant of functional recovery in SCI patients.

PMID- 29339913
TI  - The Influence of Chronic Inflammation on Peripheral Motor Nerve Conduction
      Following Spinal Cord Injury: A Randomized Clinical Trial.
AB  - Objective: To examine the potential influence of chronic inflammation on
      peripheral motor nerve function in vivo following spinal cord injury (SCI).
      Methods: This study was part of a randomized, parallel-group, controlled clinical
      trial. The study included 20 participants with varying levels and severities of
      SCI randomized (3:2) to either a treatment group, consisting of a 12-week anti
      inflammatory diet program, or control group. Outcome measures were assessed at
      baseline, 1 month, and 3 months and consisted of measures of motor nerve
      conduction velocity (NCV) and amplitude as well as markers of inflammation as
      assessed by various pro- and anti-inflammatory cytokines. Results: Despite a
      significant reduction in inflammation in the treatment group, 2-way repeated
      measures analysis of variance (ANOVA) showed no significant Group * Time
      interaction for motor NCV (p = .77) or M-wave amplitude (p = .61). Further, the
      change in motor NCV and M-wave amplitude were not shown to be associated with the
      change in inflammatory mediators as assessed via a backwards elimination multiple
      regression analysis. Conclusion: These results suggest that at physiologically
      relevant concentrations, inflammatory mediators may not have a substantial
      influence on peripheral motor nerve conduction in vivo following SCI. Future
      studies may still be warranted to examine the potential for central effects.

PMID- 29339914
TI  - Perinatal Care for Women with Spinal Cord Injuries: A Collaborative Workshop for
      Consensus on Care in Canada.
AB  - Background: In North America, there are currently no clearly defined standards of
      care for women with spinal cord injury (SCI) during the perinatal periods of
      preconception, pregnancy, labour/delivery, and postpartum. Women with SCI and
      their partners say resources specific to their needs are hard to find. Little
      evidence-informed research exists to guide clinicians in the care of women with
      SCI during pregnancy. Objectives: To further explore these gaps in knowledge and
      practices for perinatal care for women with SCI, a 1-day workshop was held in
      Vancouver, British Columbia (BC), Canada in November 2013. Methods: Twenty-nine
      attendees included women with SCI, SCI-community service providers, researchers,
      and health care providers from maternal/fetal medicine, rehabilitation,
      anesthesiology, and psychiatry. A pre-meeting online survey of stakeholders
      elucidated 3 themes: lack of knowledge for both consumers and care providers,
      gaps in access to services and information, and a need for collaboration
      throughout the perinatal journey. The workshop addressed issues of care
      providers' lack of knowledge of nonmedical issues during the perinatal period,
      physical and attitudinal barriers to access to care for women with SCI, and the
      need for better collaboration and communication between care providers, the
      latter potentially initiated by providing information to care providers through
      the women with SCI themselves. Results: Content experts attending the workshop
      collectively made recommendations for knowledge generation and research
      priorities, clinical application priorities, and the need for policy and
      guideline development in this field. Conclusion: Two information sources for
      women have since been developed and are available online.

PMID- 29339915
TI  - Minimal water-jet hydrodissection.
AB  - This paper presents a hydrodissection technique performed with high-speed pulse
      injection of only 0.1 cc liquid and assess its efficacy, safety, and the level of
      reduction in posterior capsule rupture complications in phacoemulsification
      cataract surgery. The kinetic energy of moving objects is directly proportional
      to the mass and to the square of its velocity. The high energy obtained by high
      speed pulse injection of a small amount of liquid ensures highly effective
      dissection. Since the amount of liquid is very small, the increase in intraocular
      pressure and the risk of rupture in the posterior capsule due to anterior
      capsular block are greatly reduced. More importantly, several rotations of the
      lens material in the capsule with effective hydrodissection facilitate the phases
      of phacoemulsification and irrigation/aspiration. As most capsule ruptures occur
      during these phases, the complication rate is thus reduced.

PMID- 29339916
TI  - Pediatric cataract surgery with hydrophilic acrylic intraocular lens implantation
      in Nepalese children.
AB  - Purpose: To assess the outcome of cataract surgery with hydrophilic acrylic
      intraocular lens (IOL) implantation in children with congenital and developmental
      cataracts. Method: A retrospective review of medical records of children with
      congenital or developmental cataracts who underwent cataract surgery with
      hydrophilic IOL implantation, from January 2011 to December 2014 in a tertiary
      eye hospital in Nepal. Primary posterior capsulotomy, anterior vitrectomy, and
      IOL implantation was done in children 8 years or younger, while older children
      underwent only lens aspiration and IOL implantation. Results: A total of 178 eyes
      of 120 children underwent cataract surgery with primary IOL implantation. Mean
      age at the time of surgery was 6.9 years (range: 3 months to 15 years). Average
      follow-up time was 13.7 (+/-5.9) months. Associated ocular anomalies were present
      in 84 (47.1%) eyes. Postoperative complications were found in 33 eyes (18.13%)
      with inflammatory membrane being the most common (10.1%). Two eyes (1.1%)
      developed endophthalmitis. Second intervention was needed in 12 (6.5%) eyes.
      Preoperative vision of less than 6/60 was present in 105 eyes (57.69%). Final
      best corrected visual acuity of 6/12 or better was found in 81 (44.5%) eyes.
      Conclusion: Our study shows that hydrophilic IOL is suitable for use in children.
      Results of this study are comparable with other studies on pediatric cataract
      surgeries using hydrophobic acrylic intraocular lenses. Low cost hydrophilic lens
      implantation is an effective approach in managing pediatric cataract surgery in
      developing countries like Nepal.

PMID- 29339917
TI  - Association of treatment adherence with real-life VA outcomes in AMD, DME, and
      BRVO patients.
AB  - Purpose: Real-life clinical outcomes of patients treated with anti-VEGF drugs for
      neovascular age-related macular degeneration (nAMD), diabetic macular edema
      (DME), or macular edema secondary to branch retinal vein occlusion (BRVO) are
      often inferior to results from randomized clinical trials. This observational
      cohort study investigates treatment adherence and real-life clinical outcomes
      within the first year of treatment. Patients and methods: A total of 708
      treatment-naive patients (466 nAMD, 134 DME, and 108 BRVO) were included.
      Patients were followed with a PRN treatment protocol with three intravitreal
      injections (IVIs) and a series of 3 monthly injections in case of persistent or
      recurrent disease activity, as determined by monthly follow-up exams including
      optical coherence tomographies. Occurrence of gaps of >56 days between treatments
      or follow-up (nonadherence [NA]) and the reasons for NA (patient- or center
      associated) as well as disease activity within the first 12 months of treatment
      were analyzed. Visual acuity (VA) as well as numbers and dates of optical
      coherence tomography and IVI were extracted from medical records. Results: NA
      occurred significantly more often in patients with DME (44%) than nAMD (32%) or
      BRVO (25%, p<0.01 between groups). NA was mainly patient-associated (nAMD: 80.0%,
      DME: 83.1%, BRVO: 70.4%, p=0.38 between groups). Patients with nAMD and DME and
      appropriate treatment/follow-up adherence had a better chance of significantly
      gaining or maintaining VA, respectively (19.9% vs 12.0% with 3-line-gain in nAMD
      and 1.3% vs 15.3% 3-line loss in DME; each p<0.05). NA did not correlate with VA
      outcomes in BRVO (3-line gain 30.9% vs 48.1% and 3-line loss 8.6% vs 7.4%;
      p>0.05). Conclusion: NA to treatment and follow-up regimens is a common problem
      in the management of patients with AMD and DME and limits clinical treatment
      outcomes under real-life conditions. Patients with DME have the highest risk of
      patient-associated NA, associated with a higher risk for significant VA loss.

PMID- 29339918
TI  - Comparability and repeatability of different methods of corneal astigmatism
      assessment.
AB  - Purpose: To assess the comparability and repeatability of keratometric and
      astigmatism values measured by four techniques: Orbscan IIz(r) (Bausch and Lomb),
      Lenstar LS 900(r) (Haag-Streit), Cassini(r) (i-Optics), and Total Cassini
      (anterior + posterior surface), in healthy volunteers. Patients and methods:
      Fifteen healthy volunteers (30 eyes) were assessed by the four techniques. In
      each eye, three consecutive measures were performed by the same operator.
      Keratometric and astigmatism values were recorded. The intraclass correlation
      coefficient (ICC) was used to assess comparability and repeatability. Agreement
      between measurement techniques was evaluated with Bland-Altman plots. Results:
      Comparability was high between all measurement techniques for minimum keratometry
      (K1), maximum keratometry (K2), astigmatism magnitude, and astigmatism axis, with
      ICC >0.900, except for astigmatism magnitude measured by Cassini compared to
      Lenstar (ICC =0.798) and Orbscan compared to Lenstar (ICC =0.810). However, there
      were some differences in the median values of K1 and K2 between measurement
      techniques, and the Bland-Altman plots showed a wide data spread for all
      variables, except for astigmatism magnitude measured by Cassini and Total
      Cassini. For J0 and J45, comparability was only high for J0 between Cassini and
      Orbscan. Repeatability was also high for all measurement techniques except for K2
      (ICC =0.814) and J45 (ICC =0.621) measured by Cassini. Conclusion: All
      measurement techniques showed high comparability regarding K1, K2, and
      astigmatism axis. Although posterior corneal surface is known to influence these
      measurements, comparability was high between Cassini and Total Cassini regarding
      astigmatism magnitude and axis. However, the wide data spread suggests that none
      of these devices should be used interchangeably.

PMID- 29339919
TI  - Effect of oral tranexamic acid on macular edema associated with retinal vein
      occlusion or diabetes.
AB  - Purpose: Tranexamic acid (TXA) is a widely used antifibrinolytic agent that can
      also cause a decrease in vascular permeability. We hypothesized that TXA could
      improve macular edema (ME) that is caused by an increase in retinal vascular
      permeability. The aim of this study is to evaluate the efficacy of oral TXA for
      ME associated with retinal vein occlusion (RVO) or diabetic ME (DME). Patients
      and methods: Oral TXA (1,500 mg daily for 2 weeks) was administered to patients
      with persistent ME secondary to RVO (7 eyes) and DME (7 eyes). After 2 weeks (ie,
      the final day of administration) and 6 weeks (ie, 4 weeks after the final
      administration), best-corrected visual acuity and central macular thickness (CMT)
      were measured and compared with baseline. Analyses were performed for RVO and DME
      cases. No other treatment was performed during the study period. Results: In RVO
      cases, significant improvement in CMT was found between baseline (467.7+/-121.4
      MUm) and 2-week measurements after treatment (428.7+/-110.5 MUm, p=0.024). No
      significant change was found in CMT between measurements taken at baseline and 6
      weeks after treatment. In DME cases, no significant change was found in CMT
      between measurements taken at baseline and 2 or 6 weeks after treatment. In all
      analyses of best-corrected visual acuity, no significant change was observed.
      Conclusion: The results support the hypothesis that plasmin plays a role in the
      development of ME associated with RVO, and oral TXA administration may be useful
      as an adjuvant treatment when combined with other agents such as anti-vascular
      endothelial growth factor.

PMID- 29339920
TI  - Microhook ab interno trabeculotomy, a novel minimally invasive glaucoma surgery.
AB  - Trabeculotomy (LOT) is performed to reduce the intraocular pressure in patients
      with glaucoma, both in children and adults. It relieves the resistance to aqueous
      flow by cleaving the trabecular meshwork and the inner walls of Schlemm's canal.
      Microhook ab interno LOT (uLOT), a novel minimally invasive glaucoma surgery,
      incises trabecular meshwork using small hooks that are inserted through corneal
      side ports. An initial case series reported that both uLOT alone and combination
      of uLOT and cataract surgery normalize the intraocular pressure during the early
      postoperative period in Japanese patients with glaucoma. Microhook can incise the
      inner wall of Schlemm's canal without damaging its outer wall easier than the
      regular straight knife that is used during goniotomy. Advantages of uLOT include:
      a wider extent of LOT (two-thirds of the circumference), a simpler surgical
      technique, being less invasiveness to the ocular surface, a shorter surgical time
      than traditional ab externo LOT, and no requirement for expensive devices. In
      this paper, the surgical technique of uLOT and tips of the technique are
      introduced.

PMID- 29339921
TI  - Cardiopulmonary exercise test and PaO2 in evaluation of pulmonary hypertension in
      COPD.
AB  - Background: Exercise tolerance decreases as COPD progresses. Pulmonary
      hypertension (PH) is common in COPD and may reduce performance further. COPD
      patients with and without PH could potentially be identified by cardiopulmonary
      exercise test (CPET). However, results from previous studies are diverging, and a
      unified conclusion is missing. We hypothesized that CPET combined with arterial
      blood gases is useful to discriminate between COPD outpatients with and without
      PH. Methods: In total, 93 COPD patients were prospectively included. Pulmonary
      function tests, right heart catheterization, and CPET with blood gases were
      performed. The patients were divided, by mean pulmonary artery pressure, into
      COPD-noPH (<25 mmHg) and COPD-PH (>=25 mmHg) groups. Linear mixed models (LMMs)
      were fitted to estimate differences when repeated measurements during the course
      of exercise were considered and adjusted for gender, age, and airway obstruction.
      Results: Ventilatory and/or hypoxemic limitation was the dominant cause of
      exercise termination. In LMM analyses, significant differences between COPD-noPH
      and COPD-PH were observed for PaO2, SaO2, PaCO2, ventilation, respiratory
      frequency, and heart rate. PaO2 <61 mmHg (8.1 kPa) during unloaded pedaling, the
      only load level achieved by all the patients, predicted PH with a sensitivity of
      86% and a specificity of 78%. Conclusion: During CPET, low exercise performance
      and PaO2 strongly indicated PH in COPD patients.

PMID- 29339922
TI  - Effect of rhythmic auditory cueing on gait in cerebral palsy: a systematic review
      and meta-analysis.
AB  - Auditory entrainment can influence gait performance in movement disorders. The
      entrainment can incite neurophysiological and musculoskeletal changes to enhance
      motor execution. However, a consensus as to its effects based on gait in people
      with cerebral palsy is still warranted. A systematic review and meta-analysis
      were carried out to analyze the effects of rhythmic auditory cueing on
      spatiotemporal and kinematic parameters of gait in people with cerebral palsy.
      Systematic identification of published literature was performed adhering to
      Preferred Reporting Items for Systematic Reviews and Meta-Analyses and American
      Academy for Cerebral Palsy and Developmental Medicine guidelines, from inception
      until July 2017, on online databases: Web of Science, PEDro, EBSCO, Medline,
      Cochrane, Embase and ProQuest. Kinematic and spatiotemporal gait parameters were
      evaluated in a meta-analysis across studies. Of 547 records, nine studies
      involving 227 participants (108 children/119 adults) met our inclusion criteria.
      The qualitative review suggested beneficial effects of rhythmic auditory cueing
      on gait performance among all included studies. The meta-analysis revealed
      beneficial effects of rhythmic auditory cueing on gait dynamic index (Hedge's
      g=0.9), gait velocity (1.1), cadence (0.3), and stride length (0.5). This review
      for the first time suggests a converging evidence toward application of rhythmic
      auditory cueing to enhance gait performance and stability in people with cerebral
      palsy. This article details underlying neurophysiological mechanisms and use of
      cueing as an efficient home-based intervention. It bridges gaps in the
      literature, and suggests translational approaches on how rhythmic auditory cueing
      can be incorporated in rehabilitation approaches to enhance gait performance in
      people with cerebral palsy.

PMID- 29339923
TI  - An acute bout of housework activities has beneficial effects on executive
      function.
AB  - Purpose: Although acute bouts of exercise reportedly have beneficial effects on
      executive function, inactive people may find it difficult to start exercising. In
      this study, we focused on housework activities (HAs) that generate a sense of
      accomplishment and require a mild intensity of physical activity. We examined the
      impact of an acute bout of HA on executive function and oxygenated hemoglobin
      (oxy-Hb) flow to related cortical regions. Materials and methods: Twenty-five
      participants (age, 18-21 years; mean, 19.88+/-0.60 years; six males and 19
      females) underwent two experiments, ie, HA and control experiments, which were
      conducted on different days. Participants vacuumed a dirty floor in the HA
      experiment and mimicked the same motion with an unplugged vacuum cleaner on a
      clean floor in the control experiment. Results: Heart rate recorded during the
      experiments showed no significant difference in the intensity of physical
      activity between control and HA groups. A questionnaire revealed a sense of
      accomplishment after completing the HA experiment. Participants performed the
      Stroop color-word task (SCWT) pre- and post-experiments; cortical hemodynamic
      changes were simultaneously monitored using functional near-infrared
      spectroscopy. Variation in Stroop interference scores for SCWT total response
      between pre- and post-experiments was signifi-cantly higher in the HA group than
      in the control group, and that for SCWT correct response showed a similar trend.
      Variation in the Stroop interference score for oxy-Hb flow to the right
      ventrolateral prefrontal cortex (R-VLPFC) showed the same trend. Conclusion:
      Thus, HAs may have a greater beneficial effect on executive function than other
      physical activities through the activation of PFC, including R-VLPFC.

PMID- 29339924
TI  - Quality of life and coping strategies of outpatients with a depressive disorder
      in maintenance therapy - a cross-sectional study.
AB  - Background: The quality of life (QoL) is a multidimensional view that represents
      all aspects of patient well-being in various areas of patient life. Specific
      coping strategies may be connected to both the QoL and the severity of mental
      disorder. The aim of this investigation was to examine the relationship between
      the QoL and the coping strategies of outpatients with a depressive disorder.
      Methods: Eighty-two outpatients, who met the criteria of the International
      Classification of Diseases, Tenth Revision, for a depressive disorder, were
      enrolled in the cross-sectional study. Data on sociodemographic and clinical
      variables were obtained from the medical records. Individuals filled the
      following standardized questionnaires: Quality of Life Satisfaction and Enjoyment
      Questionnaire, Stress Coping Style Questionnaire, and Clinical Global Impression.
      Multiple regression analyses with backward elimination were performed to discover
      the most influential factors contributing to QoL. Results: The participants with
      a depressive disorder showed an overuse of negative coping strategies, especially
      escape tendency and resignation. A positive self-instruction strategy was used by
      the patients less often. The coping strategies were significantly associated with
      the QoL. A more frequent use of positive coping strategies had a positive
      association with the QoL. The main factors related to QoL were the subjective
      severity of the disorder, employment, and positive coping strategies. Conclusion:
      The study confirmed the relationship between QoL and the coping strategies of
      outpatients with a depressive disorder.

PMID- 29339925
TI  - miR-136 targets MIEN1 and involves the metastasis of colon cancer by suppressing
      epithelial-to-mesenchymal transition.
AB  - MIEN1 is a novel oncogene, and it involves tumor progression in various cancer
      types, including colon cancer. However, the definite molecular mechanisms of
      MIEN1 in colon cancer progression remain to be completely elucidated. In the
      present study, bioinformatics prediction showed that miR-136 could be an upstream
      regulator of MIEN1; a luciferase assay and Western blot assay revealed that miR
      136 negatively regulates MIEN1 expression via directly targeting its 3'
      untranslated region sequence. Moreover, a functional assay using wound healing
      and transwell invasion showed that overexpressed miR-136 inhibited cell migration
      and invasion, and overexpression of MIEN1 partly rescued the above-mentioned
      effects of miR-136 in colon cancer cells. Additionally, a clinical sample assay
      showed that miR-136 expression was generally downregulated in colon cancer
      tissue, which was inversely correlated with MIEN1 expression. Furthermore, we
      found that miR-136 suppressed the Akt/NF-kappaB signaling pathway and epithelial
      to-mesenchymal transition in colon cancer. These results suggest that miR-136, as
      a tumor suppressor, acts in tumor metastasis by suppressing MIEN1 expression in
      colon cancer, providing a novel target for the treatment of colon cancer.

PMID- 29339926
TI  - Using a chronic hepatitis B Registry to support population-level liver cancer
      prevention in Sydney, Australia.
AB  - Background: Approximately 1% of Australians have chronic hepatitis B (CHB), which
      disproportionately affects people born in hepatitis B-endemic countries.
      Currently, approximately half of the people affected remain undiagnosed and
      antiviral treatment uptake is suboptimal (~5%). This increases the likelihood of
      developing end-stage disease complications, particularly hepatocellular cancer
      (HCC), and largely accounts for the significant increases in HCC incidence and
      mortality in Australia over the last decades. As our previous economic modeling
      suggested that CHB screening and treatment is cost-effective, we tested the
      feasibility of a primary care-based model of CHB diagnosis and management to
      prevent HCC. Materials and methods: From 2009 to 2016, the B Positive program
      trialed a CHB screening and management program in an area of high disease
      prevalence in Sydney, Australia. Trained local primary care providers (general
      practitioners) screened and managed their CHB patients using a purpose-built CHB
      Registry and a risk stratification algorithm, which allocated patients to ongoing
      primary care-based management or specialist referral. Results: The program
      enrolled and followed up >1,500 people (25% of the target population). Their
      median age was 48 years, with most participants being born in China (50%) or
      Vietnam (32%). The risk stratification algorithm allocated most Registry
      participants (n=847 or 79%) to primary care-based management, reducing
      unnecessary specialist referrals. The level of antiviral treatment uptake in
      Registry patients was 18%, which was the optimal level in this population group.
      Conclusion: This pilot program demonstrated that primary care-based hepatitis B
      diagnosis and management is acceptable to patients and their care providers and
      significantly increases compliance with treatment guidelines. This would suggest
      that scaling up access to hepatitis B treatment is achievable and can provide a
      means to operationalize a population-level approach to CHB management and liver
      cancer prevention.

PMID- 29339927
TI  - Factors affecting the cultural competence of visiting nurses for rural
      multicultural family support in South Korea.
AB  - Background: With the recent growth of multicultural families in the Korean
      society, the importance of the role of qualified visiting nurses in the delivery
      of culturally sensitive health care has grown dramatically. As the primary health
      care provider for multicultural families enrolled in public community-based
      health care centers, the cultural competence of visiting nurses is an essential
      qualification for the provision of quality health care for multicultural
      families, especially in rural areas. Cultural competence of visiting nurses is
      based on their cultural awareness and empathetic attitude toward multicultural
      families. This study aimed to examine the levels of cultural competence,
      empowerment, and empathy in visiting nurses, and to verify the factors that
      affect the cultural competence of visiting nurses working with rural
      multicultural families in South Korea. Methods: Employing a cross-sectional
      descriptive study design, data from 143 visiting nurses working in rural areas
      were obtained. Data collection took place between November 2011 and August 2012.
      The measurement tools included the modified Korean version of the Cultural
      Awareness Scale, the Text of Items Measuring Empowerment, and the Interpersonal
      Reactivity Index to measure the level of empathy of visiting nurses. Analyses
      included descriptive statistics, a t-test, an ANOVA, a Pearson correlation
      coefficient analysis, and a multiple linear regression analysis. Results: The
      cultural competence score of the visiting nurses was 3.07 on a 5-point Likert
      scale (SD = 0.30). The multiple regression analysis revealed that the cultural
      competence of visiting nurses was significantly influenced by experience of
      cultural education, empathy, and scores on the meaning subscale of the
      empowerment tool (R2 = 10.2%). Conclusions: Institutional support to enhance
      visiting nurses' empowerment by assuring the significance of their job and
      specific strategies to enhance their empathy would be helpful to improve the
      cultural competence of visiting nurses. Additionally, regular systematic
      education on culturally sensitive care would be helpful to enable visiting nurses
      to provide culturally sensitive care for multicultural families.

PMID- 29339928
TI  - Chemical proteomics, an integrated research engine for exploring drug-target
      phenotype interactions.

PMID- 29339930
TI  - Research evaluation support services in biomedical libraries.
AB  - Objective: The paper provides a review of current practices related to evaluation
      support services reported by seven biomedical and research libraries. Methods: A
      group of seven libraries from the United States and Canada described their
      experiences with establishing evaluation support services at their libraries. A
      questionnaire was distributed among the libraries to elicit information as to
      program development, service and staffing models, campus partnerships, training,
      products such as tools and reports, and resources used for evaluation support
      services. The libraries also reported interesting projects, lessons learned, and
      future plans. Results: The seven libraries profiled in this paper report a
      variety of service models in providing evaluation support services to meet the
      needs of campus stakeholders. The service models range from research center
      cores, partnerships with research groups, and library programs with staff
      dedicated to evaluation support services. A variety of products and services were
      described such as an automated tool to develop rank-based metrics, consultation
      on appropriate metrics to use for evaluation, customized publication and citation
      reports, resource guides, classes and training, and others. Implementing these
      services has allowed the libraries to expand their roles on campus and to
      contribute more directly to the research missions of their institutions.
      Conclusions: Libraries can leverage a variety of evaluation support services as
      an opportunity to successfully meet an array of challenges confronting the
      biomedical research community, including robust efforts to report and demonstrate
      tangible and meaningful outcomes of biomedical research and clinical care. These
      services represent a transformative direction that can be emulated by other
      biomedical and research libraries.

PMID- 29339929
TI  - Inositol depletion, GSK3 inhibition and bipolar disorder.
AB  - Valproic acid and lithium are widely used to treat bipolar disorder, a severe
      illness characterized by cycles of mania and depression. However, their efficacy
      is limited, and treatment is often accompanied by serious side effects. The
      therapeutic mechanisms of these drugs are not understood, hampering the
      development of more effective treatments. Among the plethora of biochemical
      effects of the drugs, those that are common to both may be more related to
      therapeutic efficacy. Two common outcomes include inositol depletion and GSK3
      inhibition, which have been proposed to explain the efficacy of both valproic
      acid and lithium. Here, we discuss the inositol depletion and GSK3 inhibition
      hypotheses, and introduce a unified model suggesting that inositol depletion and
      GSK3 inhibition are inter-related.

PMID- 29339931
TI  - Assessment of knowledge and skills in information literacy instruction for
      rehabilitation sciences students: a scoping review.
AB  - Objective: This scoping review investigates how knowledge and skills are assessed
      in the information literacy (IL) instruction for students in physical therapy,
      occupational therapy, or speech-language pathology, regardless of whether the
      instruction was given by a librarian. The objectives were to discover what
      assessment measures were used, determine whether these assessment methods were
      tested for reliability and validity, and provide librarians with guidance on
      assessment methods to use in their instruction in evidence-based practice
      contexts. Methods: A scoping review methodology was used. A systematic search
      strategy was run in Ovid MEDLINE and adapted for CINAHL; EMBASE; Education
      Resources Information Center (ERIC) (EBSCO); Library and Information Science
      Abstracts (LISA); Library, Information Science & Technology Abstracts (LISTA);
      and Proquest Theses and Dissertations from 1990 to January 16, 2017. Forty
      articles were included for data extraction. Results: Three major themes emerged:
      types of measures used, type and context of librarian involvement, and skills and
      outcomes described. Thirty-four measures of attitude and thirty-seven measures of
      performance were identified. Course products were the most commonly used type of
      performance measure. Librarians were involved in almost half the studies, most
      frequently as instructor, but also as author or assessor. Information literacy
      skills such as question formulation and database searching were described in
      studies that did not involve a librarian. Conclusion: Librarians involved in
      instructional assessment can use rubrics such as the Valid Assessment of Learning
      in Undergraduate Education (VALUE) when grading assignments to improve the
      measurement of knowledge and skills in course-integrated IL instruction. The
      Adapted Fresno Test could be modified to better suit the real-life application of
      IL knowledge and skills.

PMID- 29339932
TI  - Computerized versus hand-scored health literacy tools: a comparison of Simple
      Measure of Gobbledygook (SMOG) and Flesch-Kincaid in printed patient education
      materials.
AB  - Objective: The research compared and contrasted hand-scoring and computerized
      methods of evaluating the grade level of patient education materials that are
      distributed at an academic medical center in east Tennessee and sought to
      determine if these materials adhered to the American Medical Association's
      (AMA's) recommended reading level of sixth grade. Methods: Librarians at an
      academic medical center located in the heart of Appalachian Tennessee initiated
      the assessment of 150 of the most used printed patient education materials. Based
      on the Flesch-Kincaid (F-K) scoring rubric, 2 of the 150 documents were excluded
      from statistical comparisons due to the absence of text (images only).
      Researchers assessed the remaining 148 documents using the hand-scored Simple
      Measure of Gobbledygook (SMOG) method and the computerized F-K grade level
      method. For SMOG, 3 independent reviewers hand-scored each of the 150 documents.
      For F-K, documents were analyzed using Microsoft Word. Reading grade levels
      scores were entered into a database for statistical analysis. Inter-rater
      reliability was calculated using intra-class correlation coefficients (ICC).
      Paired t-tests were used to compare readability means. Results: Acceptable inter
      rater reliability was found for SMOG (ICC=0.95). For the 148 documents assessed,
      SMOG produced a significantly higher mean reading grade level (M=9.6, SD=1.3)
      than F-K (M=6.5, SD=1.3; p<0.001). Additionally, when using the SMOG method of
      assessment, 147 of the 148 documents (99.3%) scored above the AMA's recommended
      reading level of sixth grade. Conclusions: Computerized health literacy
      assessment tools, used by many national patient education material providers,
      might not be representative of the actual reading grade levels of patient
      education materials. This is problematic in regions like Appalachia because
      materials may not be comprehensible to the area's low-literacy patients. Medical
      librarians have the potential to advance their role in patient education to
      better serve their patient populations.

PMID- 29339933
TI  - Roles for librarians in systematic reviews: a scoping review.
AB  - Objective: What roles do librarians and information professionals play in
      conducting systematic reviews? Librarians are increasingly called upon to be
      involved in systematic reviews, but no study has considered all the roles
      librarians can perform. This inventory of existing and emerging roles aids in
      defining librarians' systematic reviews services. Methods: For this scoping
      review, the authors conducted controlled vocabulary and text-word searches in the
      PubMed; Library, Information Science & Technology Abstracts; and CINAHL
      databases. We separately searched for articles published in the Journal of the
      European Association for Health Information and Libraries, Evidence Based Library
      and Information Practice, the Journal of the Canadian Heath Libraries
      Association, and Hypothesis. We also text-word searched Medical Library
      Association annual meeting poster and paper abstracts. Results: We identified 18
      different roles filled by librarians and other information professionals in
      conducting systematic reviews from 310 different articles, book chapters, and
      presented papers and posters. Some roles were well known such as searching,
      source selection, and teaching. Other less documented roles included planning,
      question formulation, and peer review. We summarize these different roles and
      provide an accompanying bibliography of references for in-depth descriptions of
      these roles. Conclusion: Librarians play central roles in systematic review
      teams, including roles that go beyond searching. This scoping review should
      encourage librarians who are fulfilling roles that are not captured here to
      document their roles in journal articles and poster and paper presentations.

PMID- 29339934
TI  - Publication outcome of abstracts submitted to the American Academy of
      Ophthalmology meeting.
AB  - Objective: Abstracts submitted to meetings are subject to less rigorous peer
      review than full-text manuscripts. This study aimed to explore the publication
      outcome of abstracts presented at the American Academy of Ophthalmology (AAO)
      annual meeting. Methods: Abstracts presented at the 2008 AAO meeting were
      analyzed. Each presented abstract was sought via PubMed to identify if it had
      been published as a full-text manuscript. The publication outcome, journal impact
      factor (IF), and time to publication were recorded. Results: A total of 690
      abstracts were reviewed, of which 39.1% were subsequently published. They were
      published in journals with a median IF of 2.9 (range 0-7.2) and a median
      publication time of 426 days (range 0-2,133 days). A quarter were published in
      the journal Ophthalmology, with a shorter time to publication (median 282 vs. 534
      days, p=0.003). Oral presentations were more likely to be published than poster
      presentations (57.8% vs. 35.9%, p<0.001) and in journals with higher IFs (3.2 vs.
      2.8, p=0.02). Abstracts describing rare diseases had higher publication rates
      (49.4% vs. 38.0%, p=0.04) and were published in higher IF journals (3.7 vs. 2.9,
      p=0.03), within a shorter period of time (358 vs. 428 days, p=0.03). In
      multivariate analysis, affiliation with an institute located in the United States
      (p=0.002), abstracts describing rare diseases (p=0.03), and funded studies
      (p=0.03) were associated with publication in higher IF journals. Conclusions:
      Almost 40% of abstracts were published. Factors that correlated with publication
      in journals with higher IF were a focus on rare diseases, affiliation with a US
      institute, and funding.

PMID- 29339935
TI  - Dietetic interns' perceptions and use of evidence-based practice: an exploratory
      study.
AB  - Objective: This study explored dietetic interns' perceptions and knowledge of
      evidence-based practice (EBP), their use and observation of EBP principles during
      their clinical rotations, and their intentions to use EBP in their careers.
      Methods: A mixed methods design combining a survey and focus group was employed.
      Dietetic interns (n=16) from a large Midwestern university were recruited in
      person and via email to participate in the survey, focus group, or both.
      Perceptions and experiences of EBP were analyzed through the focus group
      (qualitative), and EBP knowledge and clinical practice behaviors were analyzed
      through the survey (quantitative). The focus group discussion was recorded,
      transcribed, and analyzed using thematic analysis. Results: Four major themes
      emerged from the focus group data: (1) observations of EBP in clinical practice,
      (2) use of EBP during clinical rotations, (3) barriers to EBP, and (4) perceived
      use of EBP as future registered dietitians. Interns considered EBP important for
      their profession and future careers. They struggled, however, with the
      discrepancies between current research and practice, and highlighted differences
      that they observed and barriers that they experienced across different clinical
      settings. Conclusions: This exploratory study is the first to examine dietetic
      interns' perceptions of and experiences with EBP in the clinical setting. Future
      research is needed to identify how dietetics educators, librarians, and
      preceptors can address the barriers that interns perceive in applying EBP in
      their internships.

PMID- 29339936
TI  - Satellite stories: capturing professional experiences of academic health sciences
      librarians working in delocalized health sciences programs.
AB  - Objective: Health sciences training programs have progressively expanded onto
      satellite campuses, allowing students the opportunity to learn in communities
      away from an academic institution's main campus. This expansion has encouraged a
      new role for librarians to assume, in that a subset of health sciences librarians
      identify as "satellite librarians" who are permanently located at a distance from
      the main campus. Due to the unique nature of this role and lack of existing data
      on the topic, the authors investigated the experiences and perceptions of this
      unique group of information professionals. Methods: An electronic survey was
      distributed to health sciences librarians via two prominent North American email
      discussion lists. Questions addressed the librarians' demographics, feelings of
      social inclusion, technological support, autonomy, professional support, and
      more. Results: Eighteen surveys were analyzed. While several respondents stated
      that they had positive working relationships with colleagues, many cited issues
      with technology, scheduling, and lack of consideration as barriers to feeling
      socially included at both the parent and local campuses. Social inclusion, policy
      creation, and collection management issues were subject to their unique
      situations and their colleagues' perceptions of their roles as satellite
      librarians. Conclusions: The results from this survey suggest that the role of
      the academic health sciences librarian at the satellite campus needs to be
      clearly communicated and defined. This, in turn, will enhance the experience for
      the librarian and provide better service to the client.

PMID- 29339937
TI  - Discrepancies among Scopus, Web of Science, and PubMed coverage of funding
      information in medical journal articles.
AB  - Objective: The overall aim of the present study was to compare the coverage of
      existing research funding information for articles indexed in Scopus, Web of
      Science, and PubMed databases. Methods: The numbers of articles with funding
      information published in 2015 were identified in the three selected databases and
      compared using bibliometric analysis of a sample of twenty-eight prestigious
      medical journals. Results: Frequency analysis of the number of articles with
      funding information showed statistically significant differences between Scopus,
      Web of Science, and PubMed databases. The largest proportion of articles with
      funding information was found in Web of Science (29.0%), followed by PubMed
      (14.6%) and Scopus (7.7%). Conclusion: The results show that coverage of funding
      information differs significantly among Scopus, Web of Science, and PubMed
      databases in a sample of the same medical journals. Moreover, we found that,
      currently, funding data in PubMed is more difficult to obtain and analyze
      compared with that in the other two databases.

PMID- 29339938
TI  - Understanding cancer survivors' information needs and information-seeking
      behaviors for complementary and alternative medicine from short- to long-term
      survival: a mixed-methods study.
AB  - Objective: The research examined complementary and alternative medicine (CAM)
      information-seeking behaviors and preferences from short- to long-term cancer
      survival, including goals, motivations, and information sources. Methods: A mixed
      methods approach was used with cancer survivors from the "Assessment of Patients'
      Experience with Cancer Care" 2004 cohort. Data collection included a mail survey
      and phone interviews using the critical incident technique (CIT). Results:
      Seventy survivors from the 2004 study responded to the survey, and eight
      participated in the CIT interviews. Quantitative results showed that CAM usage
      did not change significantly between 2004 and 2015. The following themes emerged
      from the CIT: families' and friends' provision of the initial introduction to a
      CAM, use of CAM to manage the emotional and psychological impact of cancer,
      utilization of trained CAM practitioners, and online resources as a prominent
      source for CAM information. The majority of participants expressed an interest in
      an online information-sharing portal for CAM. Conclusion: Patients continue to
      use CAM well into long-term cancer survivorship. Finding trustworthy sources for
      information on CAM presents many challenges such as reliability of source,
      conflicting information on efficacy, and unknown interactions with conventional
      medications. Study participants expressed interest in an online portal to meet
      these needs through patient testimonials and linkage of claims to the scientific
      literature. Such a portal could also aid medical librarians and clinicians in
      locating and evaluating CAM information on behalf of patients.

PMID- 29339939
TI  - Library instruction in medical education: a survey of current practices in the
      United States and Canada.
AB  - Objective: The most recent survey on instruction practices in libraries
      affiliated with accredited medical institutions in the United States was
      conducted in 1996. The present study sought to update these data, while expanding
      to include Canadian libraries. Additional analysis was undertaken to test for
      statistically significant differences between library instruction in the United
      States and Canada and between libraries affiliated with highly ranked and
      unranked institutions. Methods: A twenty-eight-question survey was distributed to
      libraries affiliated with accredited US and Canadian medical schools to assess
      what and how often librarians teach, as well as how librarians are involved in
      the curriculum committee and if they are satisfied with their contact with
      students and faculty. Quantitative data were analyzed with SAS, R, and MedCalc.
      Results: Most of the seventy-three responding libraries provided instruction,
      both asynchronously and synchronously. Library instruction was most likely to be
      offered in two years of medical school, with year one seeing the most activity.
      Database use was the most frequently taught topic, and libraries reported a
      median of five librarians providing instruction, with larger staffs offering
      slightly more education sessions per year. Libraries associated with highly
      ranked schools were slightly more likely to offer sessions that were integrated
      into the medical school curriculum in year four and to offer sessions in more
      years overall. Conclusions: In US and Canadian libraries, regardless of the rank
      of the affiliated medical school, librarians' provision of instruction in
      multiple formats on multiple topics is increasingly common.

PMID- 29339940
TI  - Applying an information literacy rubric to first-year health sciences student
      research posters.
AB  - Objective: This article describes the collection and analysis of annotated
      bibliographies created by first-year health sciences students to support their
      final poster projects. The authors examined the students' abilities to select
      relevant and authoritative sources, summarize the content of those sources, and
      correctly cite those sources. Methods: We collected images of 1,253 posters, of
      which 120 were sampled for analysis, and scored the posters using a 4-point
      rubric to evaluate the students' information literacy skills. Results: We found
      that 52% of students were proficient at selecting relevant sources that directly
      contributed to the themes, topics, or debates presented in their final poster
      projects, and 64% of students did well with selecting authoritative peer-reviewed
      scholarly sources related to their topics. However, 45% of students showed
      difficulty in correctly applying American Psychological Association (APA)
      citation style. Conclusion: Our findings demonstrate a need for instructors and
      librarians to provide strategies for reading and comprehending scholarly articles
      in addition to properly using APA citation style.

PMID- 29339941
TI  - Building capacity to encourage research reproducibility and #MakeResearchTrue.
AB  - Background: Research into study replication and reporting has led to wide concern
      about a reproducibility crisis. Reproducibility is coming to the attention of
      major grant funders, including the National Institutes of Health, which launched
      new grant application instructions regarding rigor and reproducibility in 2015.
      Study Purpose: In this case study, the authors present one library's work to help
      increase awareness of reproducibility and to build capacity for our institution
      to improve reproducibility of ongoing and future research. Case Presentation:
      Library faculty partnered with campus research leaders to create a daylong
      conference on research reproducibility, followed by a post-conference day with
      workshops and an additional seminar. Attendees came from nearly all schools and
      colleges on campus, as well as from other institutions, nationally and
      internationally. Feedback on the conference was positive, leading to efforts to
      sustain the momentum achieved at the conference. New networking and educational
      opportunities are in development. Discussion: Libraries are uniquely positioned
      to lead educational and capacity-building efforts on campus around research
      reproducibility. Costs are high and partnerships are required, but such efforts
      can lead to positive change institution-wide.

PMID- 29339942
TI  - A new hat for librarians: providing REDCap support to establish the library as a
      central data hub.
AB  - Background: REDCap, an electronic data capture tool, supports good research data
      management, but many researchers lack familiarity with the tool. While a REDCap
      administrator provided technical support and a clinical data management support
      unit provided study design support, a service gap existed. Case Presentation:
      Librarians with REDCap expertise sought to increase and improve usage through
      outreach, workshops, and consultations. In collaboration with a REDCap
      administrator and the director of the clinical data management support unit, the
      role of the library was established in providing REDCap training and
      consultations. REDCap trainings were offered to the medical center during the
      library's quarterly data series, which served as a springboard for offering
      tailored REDCap support to researchers and research groups. Conclusions:
      Providing REDCap support has proved to be an effective way to associate the
      library with data-related activities in an academic medical center and identify
      new opportunities for offering data services in the library. By offering REDCap
      services, the library established strong partnerships with the Information
      Technology Department, Clinical Data Support Department, and Compliance Office by
      filling in training gaps, while simultaneously referring users back to these
      departments when additional expertise was required. These new partnerships
      continue to grow and serve to position the library as a central data hub in the
      institution.

PMID- 29339943
TI  - The case for consistent use of medical eponyms by eliminating possessive forms.

PMID- 29339944
TI  - Building a body of knowledge: sickle cell and libraries.

PMID- 29339946
TI  - Functional Heartburn.

PMID- 29339945
TI  - Correction.
AB  - [This corrects the article on p. 240 in vol. 105, PMID: 28670211.].

PMID- 29339947
TI  - Vaccination and Health Maintenance Issues to Consider in Patients With
      Inflammatory Bowel Disease.
AB  - Patients with inflammatory bowel disease (IBD) do not receive routine preventive
      care at the same rate as the general population. IBD places patients at increased
      risk for developing vaccine-preventable illnesses. This risk is further
      exacerbated by immunosuppressive therapy. This article highlights the necessary
      vaccinations for IBD patients and the timing of vaccination for immunosuppressed
      patients, and discusses the health maintenance needs and preventive care issues
      related to heart disease, smoking, osteoporosis, mental health, cervical cancer,
      and skin cancer.

PMID- 29339949
TI  - Intragastric Balloons for Obesity Management.

PMID- 29339948
TI  - Update on Functional Heartburn.
AB  - The definition of functional heartburn has been refined over the years. It is
      currently described, based upon Rome IV criteria, as typical heartburn symptoms
      in the presence of normal upper endoscopy findings (including normal biopsies),
      normal esophageal pH testing, and a negative association between symptoms and
      reflux events. Functional heartburn is very common, affecting women more than
      men, and with reflux hypersensitivity makes up the majority of heartburn patients
      who fail twice-daily proton pump inhibitor therapy. These disorders overlap with
      other functional gastrointestinal disorders and are often accompanied by
      psychological comorbidities. Diagnosis is made by using endoscopy with esophageal
      biopsies, wireless pH capsule, pH-impedance monitoring, and high-resolution
      esophageal manometry. Additional diagnostic tools that may be of value include
      magnification endoscopy, chromoendoscopy, narrow-band imaging, autofluorescence
      imaging, mucosal impedance, impedance baseline values, and histopathology scores.
      Functional heartburn is primarily treated with neuromodulators. Psychological
      intervention and complementary and alternative medicine may also play important
      roles in the treatment of these patients.

PMID- 29339950
TI  - Beta-Catenin Staining of Hepatocellular Adenomas.

PMID- 29339951
TI  - Benefits, Concerns, and Future Directions of Biosimilars in Inflammatory Bowel
      Disease.

PMID- 29339952
TI  - Narrow-Band Imaging for Diagnosing Gastroesophageal Reflux Disease.

PMID- 29339954
TI  - Highlights in Clostridium difficile Infection From the World Congress of
      Gastroenterology at ACG 2017: October 13-18, 2017 * Orlando, Florida.

PMID- 29339953
TI  - Overview of the Updated AASLD Guidelines for the Management of HCC.

PMID- 29339955
TI  - Highlights in Functional Dyspepsia Treatment From Digestive Disease Week 2017:
      May 6-9, 2017 * Chicago, Illinois.

PMID- 29339956
TI  - CSACI position statement: prescribing sublingual immunotherapy tablets for
      aeroallergens.

PMID- 29339957
TI  - A Case of Synchronised Pupillary and Nasal Cycling: Evidence for a Central
      Autonomic Pendulum?
AB  - We previously reported that some healthy individuals show alternating anisocoria.
      We now describe one such individual who also exhibits a classic nasal cycle
      (alternating periods of nasal congestion and decongestion). We made measurements
      of his pupil asymmetry and nasal asymmetry at 21 different time points and found
      that these variables were always synchronised such that greater nasal airflow was
      invariably found on the same side as the larger pupil. We hypothesise that a
      common central oscillator may be responsible for co-modulating the sympathetic
      outflow to both nasal vessels and iris dilator muscles in some healthy
      individuals.

PMID- 29339959
TI  - Medical Cannabis, a Beneficial High in Treatment of Blepharospasm? An Early
      Observation.
AB  - The objective of this study was to observe the effect of medical cannabis in
      benign essential blepharospasm (BEB) as an adjunct to botulinum toxin. A
      retrospective chart review was performed on patients certified for medical
      cannabis use for BEB from September 2015 to May 2016. Patient demographics and
      responses, cannabis history, and severity indices were collected. Ten patients
      were certified for medical cannabis use. Five met the inclusion criteria, which
      was any patient with a diagnosis of BEB receiving standard botulinum toxin
      treatment who had started medical cannabis treatment by a registered distributor
      within the state, and was contactable by phone. Four patients discontinued use.
      Three out of four patients (75%) reported symptomatic improvement. Medical
      cannabis is an accepted therapy for muscle spastic disorders. Its potential as an
      adjunctive therapy for BEB remains unknown, and further investigations would be
      of benefit.

PMID- 29339958
TI  - Validation of Simplified Visual Acuity Testing Protocols in Amyotrophic Lateral
      Sclerosis.
AB  - High- and low-contrast visual acuity (HCVA, LCVA) are potential quantitative
      markers of neurological dysfunction in amyotrophic lateral sclerosis (ALS). The
      complex nature and duration of gold standard (GS) protocols precludes widespread
      use in neurology settings. This study compares simplified to GS visual acuity
      (VA) protocols. Monocular HCVA and LCVA were measured in ALS (n = 10) and control
      (n = 4) subjects using six protocols, varying by two chart and three refraction
      methods. Intraclass correlation coefficients between simplified and GS protocols
      ranged from 0.83 to 0.98 (HCVA, excellent agreement) and 0.56 to 0.75 (LCVA,
      moderate agreement). Differences between LCVA and GS protocols exceeded test
      retest reliability. Simplified HCVA protocols using LCD (liquid crystal display)
      tablet charts and/or pinhole correction produced valid measurements. None of the
      modified LCVA testing protocols produced valid measurements.

PMID- 29339960
TI  - Which Differences in Priming Effect Between Neglect and Hemianopia? A Case
      Description of a Bilateral Brain-Lesioned Patient.
AB  - It is widely known that visuospatial neglect and hemianopia maybe superimposed.
      We considered the differences in implicit information processing which is
      effective in patients with neglect but not with hemianopia. We then hypothesize
      that a prime-word in the neglected field should determine a semantic activation
      effect but not in a blind hemifield. Moreover eye movements could provide further
      details. In this work we considered a patient with a bilateral with the presence
      of either a left visual neglect and a right homonymous hemianopia. Our results
      supported implicit information processing in the space affected by neglect but
      not by hemianopia.

PMID- 29339961
TI  - Skew Deviation and Partial Ocular Tilt Reaction Due to Intratympanic Gentamicin
      Injection, with Review of the Literature.
AB  - Skew deviation is a rare side effect of intratympanic gentamicin injection for
      intractable Meniere's disease. When the skew deviation is accompanied by
      pathologic head tilt and ocular torsion, the result is an ocular tilt reaction
      (OTR). The authors report the case of a 56-year-old man with refractory Meniere's
      disease who developed binocular vertical diplopia following intratympanic
      gentamicin injection and was found to have skew deviation and a partial ocular
      tilt reaction. The authors also review the reported cases of skew deviation
      following intratympanic gentamicin and confirm this phenomenon, which has only
      rarely been reported in the literature.

PMID- 29339962
TI  - Three New PAX2 Gene Mutations in Patients with Papillorenal Syndrome.
AB  - Papillorenal syndrome (PAPRS; Mendelian Inheritance in Man [MIM] 120330) is an
      autosomal dominant disease characterised by the presence of congenital renal and
      optic nerve abnormalities associated with mutations of the PAX2 gene. In this
      article, the authors present four patients with PAPRS who are carriers of three
      new PAX2 mutations, as well as another patient with a possible non-pathogenic
      variant of the PAX2 gene. All patients were given a full neurophthalmological
      examination, and all patients underwent a genetic test for PAX2. Patients 1 and 2
      presented with the classic signs of PAPRS: renal disease associated with a
      congenitally abnormal optic disc, whereas patients 3 and 4 only presented with a
      congenital optic nerve abnormality and no renal involvement. In patients 1 and 2,
      the optic nerves were affected by the presence of a central excavation within the
      optic disc, absence of the central retinal artery, as well as multiple
      cilioretinal arteries radiating from the periphery of the optic disc. Bilateral
      optic nerve pits were seen in patient 3, and lastly, in patient 4 there was the
      presence of superficial gliotic tissue on the left optic disc. All patients
      presented with a missense mutation in the PAX2 gene, where in patient 4 possibly
      being only a non-pathogenic variant of the gene. In conclusion, the authors
      present two patients with classic clinical signs of PAPRS, having two new PAX2
      mutations, which until now have not been described in the current literature;
      another patient with a new PAX2 mutation showing only ocular manifestations of
      the disease, and lastly, a patient who is a carrier of a variant of the PAX2 gene
      has a congenitally abnormal optic disc, which is probably not related to PAPRS.

PMID- 29339963
TI  - Infiltrative Optic Neuropathies: Opening Doors to Sinister Pathologies.
AB  - Optic disc edema may be caused by a number of conditions. A commonly ignored but
      important aspect is the presence of "infiltration" of disc; that may closely
      mimic disc edema. Disc edema, optic nerve dysfunction and a normal appearing disc
      in any combination may occur in infiltrative optic neuropathies. Identifying disc
      infiltration can aid in diagnosis of many sinister pathologies even in the
      absence of other specific clinical features. We describe two patients presenting
      with optic nerve dysfunction and infiltrated disc appearance, which on
      investigations were found to have underlying malignancies thereby underscoring
      the importance of detecting infiltrative optic neurpathies.

PMID- 29339964
TI  - Cerebral Venous Thrombosis with Papilloedema Secondary to Skull Base
      Plasmacytoma.
AB  - A 60-year-old woman with history of multiple myeloma was in remission after stem
      cell transplant 6 years prior. She was undergoing work-up for headaches that were
      thought to be secondary to a right mastoiditis seen on magnetic resonance imaging
      (MRI). On routine eye exam, papilloedema was noted. A lumbar puncture was
      performed, with elevated opening pressure with normal constituents. She was an
      atypical age for idiopathic intracranial hypertension, and her mastoiditis raised
      concern for secondary cerebral venous sinus thrombosis. Magnetic resonance
      venography (MRV) was performed showing poor flow in the right sigmoid sinus, and
      computed tomography venography (CTV) showed lack of contrast enhancement distal
      to the right sigmoid sinus, consistent with occlusion. There was also an
      enhancing mass inferior to the right occipital bone. Biopsy confirmed recurrent
      plasma cell myeloma. She was treated with chemotherapy, radiation, and warfarin
      for presumed cerebral venous sinus thrombosis.

PMID- 29339965
TI  - Bilateral Radiation Optic Neuropathy Following Concurrent Chemotherapy and
      Radiation in Glioblastoma.
AB  - Radiation optic neuropathy (RON) is an iatrogenic complication that causes
      severe, irreversible vision loss within months to years following radiation to
      lesions close to the visual pathway. The authors describe a case of RON in
      glioblastoma after radio-sensitisation with temozolomide with sequential
      involvement of both optic nerves. This case provides a timeline for clinical and
      imaging findings with RON and specifically resolution of nerve enhancement. The
      authors also highlight the potential of an increase in incidence of RON in
      glioblastoma with advances in survival seen with greater use of second-line
      chemotherapy and even re-radiation.

PMID- 29339966
TI  - Acute diesel exhaust exposure and postural stability: a controlled crossover
      experiment.
AB  - Recent epidemiological evidence connects ambient air pollutants to adverse
      neurobehavioural effects in adults. In animal models, subchronic controlled
      exposures to diesel exhaust (DE) have also showed evidence of neuroinflammation.
      Evidence suggests that DE not only affects outcomes commonly associated with
      cognitive dysfunction, but also balance impairment. We conducted a controlled
      human exposure experiment with 28 healthy subjects (average age = 28 years (SD =
      7.1; range = 21-49); and 40% female) who were exposed to two conditions, filtered
      air (FA) and DE (300 MUg PM2.5/m3) for 120 min, in a double-blinded crossover
      study with randomized exposures separated by four weeks. Postural stability was
      assessed by the Balance Error Scoring System (BESS), a brief, easily-administered
      test of static balance. The BESS consists of a sequence of three stances
      performed on two surfaces. With hands on hips and eyes closed, each stance is
      held for 20 s. "Error" points are awarded for deviations from those stances. Pre-
      and immediately post-exposure BESS "error" point totals were calculated and the
      difference between the two timepoints were compared for each of the two exposure
      conditions. A mixed effect model assessed the significance of the association.
      While our data demonstrates a trend of reduced postural stability in response to
      exposure to DE, exposure was not significantly associated with BESS value. This
      is the first study to investigate changes in postural stability as a result of
      exposure to DE in human subjects.

PMID- 29339967
TI  - Preventing neonatal herpes infections through maternal immunization.

PMID- 29339968
TI  - Analysis of questions about use of drugs in breastfeeding to Norwegian drug
      information centres.
AB  - Background: Health professionals may advise women to either stop breastfeeding or
      drug treatment due to restrictive advice in drug monographs. Regional medicines
      information and pharmacovigilance centres in Norway (RELIS) provide free and
      industry-independent answers to questions about drugs and breastfeeding
      documented in a full-text, searchable database (RELIS database). We used the
      RELIS database to describe which health care practitioners sought information
      about medication safety in lactation, most common drugs involved, advice provided
      and which resources were used to provide the advice. Methods: A random selection
      of 100 question-answer pairs (QAPs) from the RELIS database indexed with
      "BREASTFEEDING" in the period from January 2011 to December 2015 was analysed.
      Inclusion criteria were queries from health professionals about drugs. Questions
      about herbal supplements and other exposures not classified as drugs were
      excluded. The QAPs were manually analysed for compatibility of one or several
      drugs with breastfeeding, health care profession and workplace of enquirer in
      addition to advice and search strategy used. Results: In the 100 QAPs there were
      enquires about 152 drugs. Seventy-four questions concerned a single drug, but the
      number of drugs evaluated varied between 1 and 16. Fifty-nine questions were from
      physicians, 34 from nurses or midwives, two from pharmacists and two from other
      health professionals. Questions from physicians contained 93 drug evaluations
      (61%), nurses or midwives 47 (31%) and pharmacists seven (5%). The most frequent
      categories of drugs were antidepressants, antiepileptics and immunosuppressants.
      The most asked about drugs were lamotrigine, codeine, quetiapine and
      escitalopram. Fifty-nine percent of the drugs were deemed safe while
      breastfeeding, 16% if precautions were taken and 12% not recommended. Thirty-nine
      percent of the drug evaluations used an advanced literature search strategy, and
      this was significantly (p < 0.05) more likely when the enquirer was a physician.
      Conclusions: This analysis of questions to Norwegian medicines information
      centres about medicine use in breastfeeding indicates the need for communication
      about safety of drugs affecting the nervous system, primarily to medical doctors
      and midwives. In the majority of cases the medicine information centre can
      reassure about the safety of breastfeeding while taking a drug.

PMID- 29339969
TI  - A new toolset for protein expression and subcellular localization studies in
      citrus and its application to citrus tristeza virus proteins.
AB  - Background: Transient gene expression is a powerful tool to study gene function
      in plants. In citrus, Agrobacterium transformation is the method of choice for
      transient expression studies, but this method does not work efficiently with many
      gene constructs, and there is a need for a more robust transient expression
      system in citrus leaves. Biolistic particle delivery is an alternative to
      Agrobacterium transformation, and in some plants, such as Arabidopsis, gives
      higher transformation rates in leaf tissues than Agrobacterium. Results: Here we
      describe an improved method for gene expression in epidermal cells of citrus
      leaves, using the Bio-Rad Helios gene-gun. Gene-gun bombardment of GFP-HDEL
      produced highly efficient gene expression in large number of cells and in
      different citrus varieties. We show here that transiently expressed proteins have
      maintained their functions in plants, and this is demonstrated by the subcellular
      localization of different organelle markers, and by a functional assay of
      Xanthomonas citri effector AvrGF1. To further expand the available tools for
      subcellular localization studies in citrus, we also generated a new set of
      transgenic citrus plants that contain organelle markers labelling the nuclei,
      actin and endoplasmic reticulum. Using these new tools, we were able to show that
      the coat protein of citrus tristeza virus localizes to the cytoplasm and nuclei
      when expressed in epidermal cells fused to GFP. Conclusion: We have optimized a
      new method for transient expression in citrus leaves, to give highly reproducible
      and efficient transformation without producing a high level of injury or
      artifacts to the bombarded tissue. We also generated the first set organelle
      markers for use in citrus. These fluorescent protein markers label the nucleus
      and the actin. With these new resources, protein activity and subcellular
      localization can be studied in citrus rapidly and in high throughput. The
      handheld gene-gun device can also be used in the grove to deliver therapies for
      citrus diseases, such as canker and Huanglongbing, into trees.

PMID- 29339970
TI  - A new image-based tool for the high throughput phenotyping of pollen viability:
      evaluation of inter- and intra-cultivar diversity in grapevine.
AB  - Background: Low pollen viability may limit grapevine yield under certain
      conditions, causing relevant economic losses to grape-growers. It is usually
      evaluated by the quantification of the number of viable and non-viable pollen
      grains that are present in a sample after an adequate pollen grain staining
      procedure. Although the manual counting of both types of grains is the simplest
      and most sensitive approach, it is a laborious and time-demanding process. In
      this regard, novel image-based approaches can assist in the objective, accurate
      and cost-effective phenotyping of this trait. Results: Here, we introduce
      PollenCounter, an open-source macro implemented as a customizable Fiji tool for
      the high-throughput phenotyping of pollen viability. This tool splits RGB images
      of stained pollen grains into its primary channels, retaining red and green color
      fractionated images (which contain information on total and only viable pollen
      grains, respectively) for the subsequent isolation and counting of the regions of
      interest (pollen grains). This framework was successfully used for the analysis
      of pollen viability of a high number of samples collected in a large collection
      of grapevine cultivars. Results revealed a great genetic variability, from
      cultivars having very low pollen viability (like Corinto Bianco; viability: 14.1
      +/- 1.3%) to others with a very low presence of sterile pollen grains (Cuelga;
      viability: 98.2 +/- 0.5%). A wide range of variability was also observed among
      several clones of cv. Tempranillo Tinto (from 97.9 +/- 0.9 to 60.6 +/- 5.9%, in
      the first season). Interestingly, the evaluation of this trait in a second season
      revealed differential genotype-specific sensitivity to environment. Conclusions:
      The use of PollenCounter is expected to aid in different areas, including
      genetics research studies, crop improvement and breeding strategies that need of
      fast, precise and accurate results. Considering its flexibility, it can be used
      not only in grapevine, but also in other species showing a differential staining
      of viable and non-viable pollen grains. The wide phenotypic diversity observed at
      a species level, together with the identification of specific cultivars and
      clones largely differing in this trait, pave the way of further analyses aimed to
      understand the physiological and genetic causes driving to male sterility in
      grapevine.

PMID- 29339971
TI  - Terzyme: a tool for identification and analysis of the plant terpenome.
AB  - Background: Terpenoid hydrocarbons represent the largest and most ancient group
      of phytochemicals, such that the entire chemical library of a plant is often
      referred to as its 'terpenome'. Besides having numerous pharmacological
      properties, terpenes contribute to the scent of the rose, the flavors of cinnamon
      and the yellow of sunflowers. Rapidly increasing -omics datasets provide an
      unprecedented opportunity for terpenome detection, paving the way for automated
      web resources dedicated to phytochemical predictions in genomic data. Results: We
      have developed Terzyme, a predictive algorithm for identification, classification
      and assignment of broad substrate unit to terpene synthase (TPS) and prenyl
      transferase (PT) enzymes, known to generate the enormous structural and
      functional diversity of terpenoid compounds across the plant kingdom. Terzyme
      uses sequence information, plant taxonomy and machine learning methods for
      predicting TPSs and PTs in genome and proteome datasets. We demonstrate a
      significant enrichment of the currently identified terpenome by running Terzyme
      on more than 40 plants. Conclusions: Terzyme is the result of a rigorous analysis
      of evolutionary relationships between hundreds of characterized sequences of TPSs
      and PTs with known specificities, followed by analysis of genome-wide gene
      distribution patterns, ontology based clustering and optimization of various
      parameters for building accurate profile Hidden Markov Models. The predictive
      webserver and database is freely available at http://nipgr.res.in/terzyme.html
      and would serve as a useful tool for deciphering the species-specific
      phytochemical potential of plant genomes.

PMID- 29339972
TI  - Evaluation of green tea extract as a safe personal hygiene against viral
      infections.
AB  - Background: Viral infections often pose tremendous public health concerns as well
      as economic burdens. Despite the availability of vaccines or antiviral drugs,
      personal hygiene is considered as effective means as the first-hand measure
      against viral infections. The green tea catechins, in particular,
      epigallocatechin-3-gallate (EGCG), are known to exert potent antiviral activity.
      In this study, we evaluated the green tea extract as a safe personal hygiene
      against viral infections. Results: Using the influenza virus A/Puerto Rico/8/34
      (H1N1) as a model, we examined the duration of the viral inactivating activity of
      green tea extract (GTE) under prolonged storage at various temperature
      conditions. Even after the storage for 56 days at different temperatures, 0.1%
      GTE completely inactivated 106 PFU of the virus (6 log10 reduction), and 0.01%
      and 0.05% GTE resulted in 2 log10 reduction of the viral titers. When
      supplemented with 2% citric acid, 0.1% sodium benzoate, and 0.2% ascorbic acid as
      anti-oxidant, the inactivating activity of GTE was temporarily compromised during
      earlier times of storage. However, the antiviral activity of the GTE was steadily
      recovered up to similar levels with those of the same concentrations of GTE
      without the supplements, effectively prolonging the duration of the virucidal
      function over extended period. Cryo-EM and DLS analyses showed a slight increase
      in the overall size of virus particles by GTE treatment. The results suggest that
      the virucidal activity of GTE is mediated by oxidative crosslinking of catechins
      to the viral proteins and the change of physical properties of viral membranes.
      Conclusions: The durability of antiviral effects of GTE was examined as solution
      type and powder types over extended periods at various temperature conditions
      using human influenza A/H1N1 virus. GTE with supplements demonstrated potent
      viral inactivating activity, resulting in greater than 4 log10 reduction of viral
      titers even after storage for up to two months at a wide range of temperatures.
      These data suggest that GTE-based antiviral agents could be formulated as a safe
      and environmentally friendly personal hygiene against viral infections.

PMID- 29339973
TI  - One-step production of C6-C8 carboxylates by mixed culture solely grown on CO.
AB  - Background: This study aimed at producing C6-C8 medium-chain carboxylates (MCCAs)
      directly from gaseous CO using mixed culture. The yield and C2-C8 product
      composition were investigated when CO was continuously fed with gradually
      increasing partial pressure. Results: The maximal concentrations of n-caproate, n
      heptylate, and n-caprylate were 1.892, 1.635, and 1.033 mmol L-1, which were
      achieved at the maximal production rates of 0.276, 0.442, and 0.112 mmol L-1 day
      1, respectively. Microbial analysis revealed that long-term acclimation and high
      CO partial pressure were important to establish a CO-tolerant and CO-utilizing
      chain-elongating microbiome, rich in Acinetobacter, Alcaligenes, and
      Rhodobacteraceae and capable of forming MCCAs solely from CO. Conclusions: These
      results demonstrated that carboxylate and syngas platform could be integrated in
      a shared growth vessel, and could be a promising one-step technique to convert
      gaseous syngas to preferable liquid biochemicals, thereby avoiding the necessity
      to coordinate syngas fermentation to short-chain carboxylates and short-to-medium
      chain elongation. Thus, this method could provide an alternative solution for the
      utilization of waste-derived syngas and expand the resource of promising
      biofuels.

PMID- 29339974
TI  - Multidisciplinary treatment of patients with diabetes and hypertension:
      experience of a Brazilian center.
AB  - Background: Although multidisciplinary treatment is recommended for type 2
      diabetes mellitus and hypertension (HTN), there is a lack of scientific
      literature supporting the hypothesis of extending this treatment strategy to
      patients with both diabetes and HTN. Aiming to report results of long-term
      multidisciplinary treatment for these patients and identify strategies to improve
      their management, we conducted this study. Methods: Data of patients with
      diabetes and HTN with regular follow-up visits in a multidisciplinary HTN
      treatment center from Brazil's Midwest were retrospectively assessed. Patients >=
      18 years enrolled in the service by June 2017 with a minimum of three visits were
      included. Anthropometric, blood pressure (BP), laboratory, pharmacological
      treatment, lifestyle, and cardiovascular events data were collected from first
      (V1), intermediate (V2) and most recent (V3) visits to the service. BP < 130 * 80
      mmHg, LDL-cholesterol (LDL-C) < 70 mg/dL and HbA1C < 7.0% were defined as
      treatment targets. Wilcoxon signed-rank test was used to compare variables along
      study visits. A linear regression model was built to identify variables
      associated with better overall patient control. Results: A total of 162 patients
      were included (mean age of 56.5 +/- 10.8 years). Median follow-up time was 60
      (IQR 40-109) months, 80.2% of the sample was female and 83.3% had no
      cardiovascular event history. BP, total cholesterol, LDL-C, triglycerides and
      HbA1C values showed a significant trend to improve along the study visits (p <
      0.001). Growing trend in aspirin (p = 0.045) and statins (p < 0.001) use was
      found, in addition to treatment compliance increase (p < 0.001). Significant
      improvement trends in BP (p < 0.001), LDL-C (p = 0.004) and HbA1C (p = 0.002)
      control were also found across visits. Control rates of BP, LDL-C and HbA1C in
      combination were low in V1, V2 and V3 (1.2, 1.9 and 6.8%, respectively), but
      showed significant improvement trend (p < 0.001). Treatment compliance (beta
      coefficient = 1.20; 95% CI 1.07-1.34; p < 0.001) was positively associated with
      better overall patients control. Conclusions: Multidisciplinary treatment of
      patients with diabetes and HTN significantly improved clinical and laboratory
      parameters, despite ageing of population evaluated. Although combined control of
      HbA1C, BP and LDL-cholesterol increased along follow-up, management of all these
      three conditions needs to improve, and focus on treatment compliance should be
      given to attain this goal.

PMID- 29339975
TI  - Genetic polymorphisms of antioxidant enzymes CAT and SOD affect the outcome of
      clinical, biochemical, and anthropometric variables in people with obesity under
      a dietary intervention.
AB  - Background: Genetic polymorphisms of antioxidant enzymes CAT, GPX, and SOD are
      involved in the etiology of obesity and its principal comorbidities. The aim of
      the present study was to analyze the effect of aforementioned SNPs over the
      output of several variables in people with obesity after a nutritional
      intervention. The study included 92 Mexican women, which received a dietary
      intervention by 3 months. Participants were genotyped and stratified into two
      groups: (1) carriers; mutated homozygous plus heterozygous (CR) and (2)
      homozygous wild type (WT). A comparison between CR and WT was done in clinical
      (CV), biochemical (BV), and anthropometric variables (AV), at the beginning and
      at the end of the intervention. Results: Participants (n = 92) showed
      statistically significant differences (p < 0.05) at the end of the nutritional
      intervention in several CV, BV, and AV. However, two kinds of responses were
      observed after genotyping participants: (A) CR and WT showed statistically
      significant differences (p < 0.05) in several CV, BV, and AV for the SNPs 599C>T
      GPX1 (rs1050450), - 251A>G SOD1 (rs2070424), and - 262C>T CAT (rs1001179). (B)
      Only CR showed statistically changes (p < 0.05) in several CV, BV, and AV for the
      SNPs - 21A>T CAT (rs7943316) and 47C>T SOD2 (rs4880). The dietary intervention
      effect was statistically significantly between the polymorphisms of 47C>T SOD2
      and BMI, SBP, TBARS, total cholesterol, and C-LCL (p < 0.05) and between the
      polymorphisms of - 21A>T CAT (rs7943316) and SBP, DBP, total cholesterol, and
      atherogenic index (p < 0.05). Conclusion: People with obesity display different
      response in several CV, BV, and AV after a nutritional intervention, depending on
      the antioxidant genetic background of SOD and CAT enzymes.

PMID- 29339976
TI  - Detection of dioxin-induced demethylation of mouse Cyp1a1 gene promoter by a new
      labeling method for short DNA fragments possessing 5'-methylcytosine at the end.
AB  - Environmental factors stimulate alteration of DNA methylation level.
      Investigation of the genome-wide DNA methylation status is important for
      environmental health studies. We here designed a genomic DNA amplification and
      labeling protocol using a methylation-sensitive restriction enzyme HinP1 I. This
      method can specifically amplify genomic DNA fragments possessing methyl-CpG at
      the end. The fragments are a relatively short size and dominantly located on CpG
      islands. By using the samples prepared by this method, a dioxin-induced change in
      the methylation level of the mouse Cyp1a1 promoter was successfully evaluated
      using oligonucleotide probes covalently bound onto a glass plate. The method
      developed in this paper would be useful for other genome-wide analysis platforms
      for the large scale epigenome-wide association studies (EWAS) including human
      epidemiological samples.

PMID- 29339977
TI  - Necessity for retrospective evaluation of past-positive chemicals in in vitro
      chromosomal aberration tests using recommended cytotoxicity indices.
AB  - We have demonstrated that retrospective evaluation of existing data of in vitro
      chromosomal aberration test using the new cytotoxicity indices RICC (relative
      increase in cell count) or RPD (relative population doubling) reduces the false
      positive rate. We have constructed an algorithm to predict the likelihood that
      past-positive results would differ when retested accordingly. Here, we emphasize
      the importance of reviewing existing in vitro chromosomal aberration test
      results. The present Letter not only supports the rediscovery of potentially
      useful chemicals excluded from further development as a result of
      misclassification due to in vitro false-positive results, but also contributes to
      the development of a precise Quantitative Structure-Activity Relationship (QSAR)
      model by providing an appropriate training data-set. Furthermore, re-evaluation
      is expected to provide novel insights into underlying mechanisms and/or key
      structures involved in the development of chromosomal aberrations.

PMID- 29339978
TI  - Increase of somatic cell mutations in oxidative damage-sensitive drosophila.
AB  - Background: Oxidative damage is an important genotoxic source for almost all
      organisms. To efficiently detect mutations induced by oxidative damage, we
      previously developed a urate-null Drosophila strain. Using this Drosophila
      strain, we showed the mutagenic activity of environmental cigarette smoke (ECS)
      and the herbicide paraquat, which are known to produce reactive oxygen species
      (ROS). In the present study, we examined the mutagenic activities of carcinogenic
      mutagens that are considered to cause mutations by adduct formation, alkylation,
      or crosslinking of cellular DNA in the oxidative damage-sensitive Drosophila to
      evaluate how the oxidative damage induced by these mutagens is involved in
      causing mutations. In addition, we evaluated whether these oxidative damage
      sensitive flies may be useful for mutation assays. Methods: We performed the wing
      spot test in oxidative damage-sensitive Drosophila (urate-null strains) to
      examine the mutagenicity of 2-amino-3,8-dimethylimidazo[4,5-f]-quinoxaline
      (MeIQx), mitomycin C (MMC), 4-nitroquinoline N-oxide (4NQO), N-nitrosodimethyl
      amine (NDMA), and N-nitrosodiethylamine (NDEA). We also observed the mutagenicity
      of X-ray irradiation as a control in which mutations should be mainly caused by
      oxidative damage. Results: As expected, the mutagenic activity of X-ray
      irradiation was higher in the urate-null Drosophila than in the wild-type
      Drosophila. The mutagenic activities of the tested compounds were also higher in
      the urate-null Drosophila than in the wild-type Drosophila. In experiments using
      another urate-null strain, the mutagenicity of N-nitrosodialkylamines was also
      higher in the urate-null flies than in the wild-type ones. Conclusions: The
      tested compounds in this study were more mutagenic in urate-null Drosophila than
      in wild-type Drosophila. It was supposed that ROS were generated and that the ROS
      might be involved in mutagenesis. The present results support the notion that in
      addition to causing DNA lesions via adduct formation, alkylation, or DNA
      crosslinking, these mutagens also cause mutations via ROS-induced DNA damage. As
      such, urate-null Drosophila appear to be useful for detecting the mutagenic
      activity of various mutagens, especially those that produce reactive oxygen. If
      the mutation rate increases on a mutation assay using urate-null Drosophila, it
      might suggest that the mutagen generates ROS, and that the produced ROS is
      involved in causing mutations.

PMID- 29339980
TI  - Re: The Integration of Internal and External Training Load Metrics in Hurling -
      Interpretation Beyond a Significant Relationship Required.

PMID- 29339979
TI  - BRCA1 and BRCA2 mutation spectrum - an update on mutation distribution in a large
      cancer genetics clinic in Norway.
AB  - Background: Founder mutations in the two breast cancer genes, BRCA1 and BRCA2,
      have been described in many populations, among these are Ashkenazi-Jewish,
      Polish, Norwegian and Icelandic. Founder mutation testing in patients with
      relevant ancestry has been a cost-efficient approach in such populations. Four
      Norwegian BRCA1 founder mutations were defined by haplotyping in 2001, and
      accounted for 68% of BRCA1 mutation carriers at the time. After 15 more years of
      genetic testing, updated knowledge on the mutation spectrum of both BRCA1 and
      BRCA2 in Norway is needed. In this study, we aim at describing the mutation
      spectrum and frequencies in the BRCA1/2 carrier population of the largest clinic
      of hereditary cancer in Norway. Methods: A total of 2430 BRCA1 carriers from 669
      different families, and 1092 BRCA2 carriers from 312 different families were
      included in a quality of care study. All variants were evaluated regarding
      pathogenicity following ACMG/ENIGMA criteria. The variants were assessed in
      AlaMut and supplementary databases to determine whether they were known to be
      founder mutations in other populations. Results: There were 120 different BRCA1
      and 87 different BRCA2 variants among the mutation carriers. Forty-six per cent
      of the registered BRCA1/2 families (454/981) had a previously reported Norwegian
      founder mutation. The majority of BRCA1/2 mutations (71%) were rare, each found
      in only one or two families. Fifteen per cent of BRCA1 families and 25% of BRCA2
      families had one of these rare variants. The four well-known Norwegian BRCA1
      founder mutations previously confirmed through haplotyping were still the four
      most frequent mutations in BRCA1 carriers, but the proportion of BRCA1 mutation
      carriers accounted for by these mutations had fallen from 68 to 52%, and hence
      the founder effect was weaker than previously described. Conclusions: The
      spectrum of BRCA1 and BRCA2 mutations in the carrier population at Norway's
      largest cancer genetics clinic is diverse, and with a weaker founder effect than
      previously described. As a consequence, retesting the families that previously
      have been tested with specific tests/founder mutation tests should be a
      prioritised strategy to find more mutation positive families and possibly prevent
      cancer in healthy relatives.

PMID- 29339981
TI  - Using Bilateral Functional and Anthropometric Tests to Define Symmetry in Cross
      Country Skiers.
AB  - The aim of this study was to evaluate the symmetry of anthropometry and muscle
      function in cross-country skiers and their association to vertical jumping power.
      Twenty cross-country skiers were recruited (21.7 +/- 3.8 yrs, 180.6 +/- 7.6 cm,
      73.2 +/- 7.6 kg). Anthropometric data was obtained using an iDXA scan. VO2max was
      determined using the diagonal stride technique on a ski treadmill. Bilateral
      functional tests for the upper and lower body were the handgrip and standing heel
      rise tests. Vertical jump height and power were assessed with a counter movement
      jump. Percent asymmetry was calculated using a symmetry index and four absolute
      symmetry index levels. At a group level the upper body was more asymmetrical with
      regard to lean muscle mass (p = 0.022, d = 0.17) and functional strength (p =
      0.019, d = 0.51) than the lower body. At an individual level the expected
      frequencies for absolute symmetry level indexes showed the largest deviation from
      zero for the heel-rise test (chi2 = 16.97, p = 0.001), while the leg lean mass
      deviated the least (chi2 = 0.42, p = 0.517). No relationships were observed
      between absolute symmetry level indexes of the lower body and counter movement
      jump performance (p > 0.05). As a group the skiers display a more asymmetrical
      upper body than lower body regarding muscle mass and strength. Interestingly at
      the individual level, despite symmetrical lean leg muscle mass the heel-rise test
      showed the largest asymmetry. This finding indicates a mismatch in muscle
      function for the lower body.

PMID- 29339982
TI  - Relationships between Mechanical Variables in the Traditional and Close-Grip
      Bench Press.
AB  - The study aim was to determine relationships between mechanical variables in the
      one-repetition maximum (1RM) traditional bench press (TBP) and close-grip bench
      press (CGBP). Twenty resistance-trained men completed a TBP and CGBP 1RM. The TBP
      was performed with the preferred grip; the CGBP with a grip width of 95%
      biacromial distance. A linear position transducer measured: lift distance and
      duration; work; and peak and mean power, velocity, and force. Paired samples t
      tests (p < 0.05) compared the 1RM and mechanical variables for the TBP and CGBP;
      effect sizes (d) were also calculated. Pearson's correlations (r; p < 0.05)
      computed relationships between the TBP and CGBP. 1RM, lift duration, and mean
      force were greater in the TBP (d = 0.30-3.20). Peak power and velocity was
      greater for the CGBP (d = 0.50-1.29). The 1RM TBP correlated with CGBP 1RM,
      power, and force (r = 0.685-0.982). TBP work correlated with CGBP 1RM, lift
      distance, power, force, and work (r = 0.542-0.931). TBP power correlated with
      CGBP 1RM, power, force, velocity, and work (r = 0.484-0.704). TBP peak and mean
      force related to CGBP 1RM, power, and force (r = 0.596-0.980). Due to
      relationships between the load, work, power, and force for the TBP and CGBP, the
      CGBP could provide similar strength adaptations to the TBP with long-term use.
      The velocity profile for the CGBP was different to that of the TBP. The CGBP
      could be used specifically to improve high-velocity, upper-body pushing
      movements.

PMID- 29339983
TI  - Analysis of the Hamstring Muscle Activation During two Injury Prevention
      Exercises.
AB  - The aim of this study was to perform an electromyographic and kinetic comparison
      of two commonly used hamstring eccentric strengthening exercises: Nordic Curl and
      Ball Leg Curl. After determining the maximum isometric voluntary contraction of
      the knee flexors, ten female athletes performed 3 repetitions of both the Nordic
      Curl and Ball Leg Curl, while knee angular displacement and electromyografic
      activity of the biceps femoris and semitendinosus were monitored. No significant
      differences were found between biceps femoris and semitendinosus activation in
      both the Nordic Curl and Ball Leg Curl. However, comparisons between exercises
      revealed higher activation of both the biceps femoris (74.8 +/- 20 vs 50.3 +/-
      25.7%, p = 0.03 d = 0.53) and semitendinosus (78.3 +/- 27.5 vs 44.3 +/- 26.6%, p
      = 0.012, d = 0.63) at the closest knee angles in the Nordic Curl vs Ball Leg
      Curl, respectively. Hamstring muscles activation during the Nordic Curl
      increased, remained high (>70%) between 60 to 40 degrees  of the knee angle and
      then decreased to 27% of the maximal isometric voluntary contraction at the end
      of movement. Overall, the biceps femoris and semitendinosus showed similar
      patterns of activation. In conclusion, even though the hamstring muscle
      activation at open knee positions was similar between exercises, the Nordic Curl
      elicited a higher hamstring activity compared to the Ball Leg Curl.

PMID- 29339984
TI  - Functional vs. Traditional Analysis in Biomechanical Gait Data: An Alternative
      Statistical Approach.
AB  - In human motion studies, discrete points such as peak or average kinematic values
      are commonly selected to test hypotheses. The purpose of this study was to
      describe a functional data analysis and describe the advantages of using
      functional data analyses when compared with a traditional analysis of variance
      (ANOVA) approach. Nineteen healthy participants (age: 22 +/- 2 yrs, body height:
      1.7 +/- 0.1 m, body mass: 73 +/- 16 kg) walked under two different conditions:
      control and pain+effusion. Pain+effusion was induced by injection of sterile
      saline into the joint capsule and hypertonic saline into the infrapatellar fat
      pad. Sagittal-plane ankle, knee, and hip joint kinematics were recorded and
      compared following injections using 2*2 mixed model ANOVAs and FANOVAs. The
      results of ANOVAs detected a condition * time interaction for the peak ankle
      (F1,18 = 8.56, p = 0.01) and hip joint angle (F1,18 = 5.77, p = 0.03), but did
      not for the knee joint angle (F1,18 = 0.36, p = 0.56). The functional data
      analysis, however, found several differences at initial contact (ankle and knee
      joint), in the mid-stance (each joint) and at toe off (ankle). Although a
      traditional ANOVA is often appropriate for discrete or summary data, in
      biomechanical applications, the functional data analysis could be a beneficial
      alternative. When using the functional data analysis approach, a researcher can
      (1) evaluate the entire data as a function, and (2) detect the location and
      magnitude of differences within the evaluated function.

PMID- 29339985
TI  - Butterfly Sprint Swimming Technique, Analysis of Somatic and Spatial-Temporal
      Coordination Variables.
AB  - The aim of this study was to investigate somatic properties and force production
      of leg extensor muscles measured in the countermovement jump test (CMJ), as well
      as to analyse kinematic variables of sprint surface butterfly swimming. Thirty
      four male competitive swimmers were recruited with an average age of 19.3 +/-
      1.83 years. Their average body height (BH) was 183.7 +/- 5.93 cm, body fat
      content 10.8 +/- 2.64% and body mass (BM) 78.3 +/- 5.0 kg. Length measurements of
      particular body segments were taken and a counter movement jump (CMJ) as well as
      an all-out 50 m butterfly speed test were completed. The underwater movements of
      the swimmers' bodies were recorded with a digital camera providing side-shots. We
      registered a significant relationship between body mass (r = 0.46), lean body
      mass (r = 0.48) and sprint surface butterfly swimming (VSBF). The anaerobic power
      measured in the CMJ test, total body length (TBL) as well as upper and lower
      extremity length indices did not influence swimming speed significantly. The
      temporal entry-kick index (the time ratio between the first kick and arm entry)
      significantly influenced VSBF (r = -0.45). Similarly, medium power of the
      coefficient was indicated between a) stroke rate kinematics (SR), b) duration of
      the first leg kick (LP1), c) air phase duration of arm recovery (Fly-arm), and
      VSBF (r = 0.40; r = 0.40 and r = 0.41, respectively). The entry-kick temporal
      index showed that, in the butterfly cycle, an appropriately early executed
      initial kick when compared to arm entry was associated with a longer arm
      propulsion phase, which in turn was associated with minimizing resistive gliding
      phases and enabled relatively longer and less resistive air arm recovery (higher
      value of the fly-arm index). The higher value of SR kinematic was another
      important element of the best butterfly results in this study.

PMID- 29339987
TI  - Physiological Demands, Morphological Characteristics, Physical Abilities and
      Injuries of Female Soccer Players.
AB  - The popularity of female soccer is increasing as well as the number of females
      playing soccer. Similarly, over the last twenty or so years, research in soccer
      has increased significantly, but a large disparity exists in the volume of
      studies involving male and female players. As a consequence of this, female
      players remain less well understood compared to males. The purpose of the present
      narrative review was to describe morphological characteristics, physiological
      demands, physical abilities and injuries in female soccer players. Physiological
      demands are similar between men's and women's soccer, but competitive women's
      matches were characterized by nearly 33% less distance covered, although at
      higher intensity levels (maximum speeds greater than 15 km/h) than typically
      found in the men's game. Sub-elite female players also tended to run less at
      higher intensity levels at the end of both halves in comparison with elite female
      players. High intensity running is an important factor of success in soccer since
      many critical moments of the game occur under this condition. The ability to
      rapidly change direction also determined elite, sub-elite and amateur levels. The
      implementation of functional training, which focused on soccer-specific drills
      and plyometric exercises, to improve explosive power, may improve conditioning in
      female soccer players as well as decrease the risk of injuries which was 3-8
      times higher in females compared to males. This review presents an in-depth
      overview of the most influential factors for determining success in female
      soccer.

PMID- 29339986
TI  - Seeking Optimal Nutrition for Healthy Body Mass Reduction among Former Athletes.
AB  - The aim of the study was to investigate the efficacy of 6 week Mediterranean diet
      or 30% calorie restriction on the fatty acid profile and eicosanoids
      (hydroxyoctadecadienoi acids and hydroxyeicosatetraenoic acids) concentration.
      Furthermore, basic biochemical variables such as insulin, glucose, HOMA-IR, and a
      lipid profile were estimated. The study enrolled 94 Caucasian former athletes
      aged 20-42, with body height of 179 +/- 16.00 cm and body mass of 89.26 +/- 13.25
      kg who had not been active for at least 5 years. The subjects were randomly
      assigned to one of the three intervention groups: CR group - the 30% calorie
      restriction (n = 32), MD group - the Mediterranean diet (n = 34), and C group - a
      control group (n = 28). The pattern of nutrition was analysed before and after
      the experiment using the 72 h food diaries. In order to evaluate the effect of
      diet intervention, the following variables were measured: anthropometrics, basic
      biochemical variables (insulin, fasting glucose, HOMA-IR, lipid profile), fatty
      acids and their blood derivatives profiles. The CR group showed significantly
      lower levels of several biochemical variables, i.e., BMI, total cholesterol LDL,
      TG, total lipids, insulin and HOMA - IR (p < 0.05). Subjects consuming the MD
      diet significantly decreased their BMI and reduced the level of total lipids (p <
      0.05). We did not find any significant changes in the C group. The analysis of
      the fatty acid profile revealed that the CR group had a significantly decreased
      EPA level (p < 0.05). The MD group showed a significantly increased level of the
      DHA (p < 0.05) and improvement in the omega - 3 index (p < 0.05). Subjects
      following the MD also showed significantly lower concentrations of 15 -
      hydroxyicosatetraenoic acid (15-HETE). We did not observe any significant
      differences between the CR and C groups. Within short time, calorie restriction
      helps to improve lipid variables and insulin resistance. The MD diet seems to be
      more advantageous in the decrease of inflammation, but does not improve basic
      biochemical variables. We can conclude that calorie restriction can be a good
      choice for former athletes, although EPA and DHA supplementation is needed.

PMID- 29339988
TI  - Impact of Futsal and Swimming Participation on Bone Health in Young Athletes.
AB  - Physical activity plays a crucial role in bone mass acquisition during childhood
      and adolescence, with weightbearing and high-impact sport activities being more
      beneficial. This study sought to evaluate the impact of different sports
      activities on bone mineral density and content in male Portuguese athletes.
      Seventy adolescent boys (aged 12-15 years) including 28 futsal players (FG), 20
      swimmers (SG) and 22 non-athletic adolescents used as control subjects (CG),
      participated in the current study. Areal bone mineral density (aBMD) and areal
      bone mineral content (aBMC) were measured by dual energy x-ray absorptiometry
      (DEXA). Futsal players had significantly higher aBMD (lumbar spine - FG: 0.95 +/-
      0.18, SG: 0.80 +/- 0.13, CG: 0.79 +/- 0.13 g/cm2, p = 0.001; pelvis - FG: 1.17 +/
      0.21, SG: 0.91 +/- 0.12, CG: 0.98 +/- 0.10 g/cm2, p < 0.001; lower limbs - FG:
      1.21 +/- 0.19, SG: 0.97 +/- 0.10, CG: 0.99 +/- 0.09 g/cm2, p < 0.001) and aBMC
      (lumbar spine - FG: 51.07 +/- 16.53, SG: 40.19 +/- 12.47, CG: 40.50 +/- 10.53 g,
      p = 0.013; pelvis - FG: 299.5 +/- 110.61, SG: 170.02 +/- 55.82, CG: 183.11 +/-
      46.78 g, p < 0.001; lower limbs - FG: 427.21 +/- 117.11, SG: 300.13 +/- 76.42,
      CG: 312.26 +/- 61.86 g/cm2, p < 0.001) than swimmers and control subjects. Data
      suggest that futsal, as a weightbearing and high or odd-impact sport, may improve
      bone mass during childhood and adolescence.

PMID- 29339989
TI  - Association between Match Activity Variables, Measures of Fatigue and
      Neuromuscular Performance Capacity Following Elite Competitive Soccer Matches.
AB  - The aim of the study was to assess the relationships between match activity
      variables, subsequent fatigue and neuromuscular performance capacity in elite
      soccer players. Subjects (n = 10) were professional soccer players participating
      in the English Championships. Match activity variables and markers of fatigue
      status were measured before and following two matches. Creatine kinase (CK) and
      muscle soreness were measured at baseline, immediately following, as well as 40
      and 64 h post-match. Countermovement jump performance and perceived ratings of
      wellness were measured at baseline, then 40 and 64 h post-match. Relationships
      were shown between CK and the total number of accelerations and decelerations
      immediately (r = 0.63; large), 40 h (r = 0.45; moderate) and 64 h post-match (r =
      0.35; moderate) (p < 0.05). Relationships between CK and total sprint distance (r
      = 0.39; moderate) and the number of sprints (r = 0.35; moderate) 40 h post-match
      (p < 0.05) were observed. Furthermore, relationships were shown between the
      perceived rating of wellness and number of accelerations 40 (r = 0.52; large) and
      64 h (r = 0.40; moderate) post-match, sprint distance 40 h post-match (r = 0.40;
      moderate) and the total number of sprints 40 h post-match (r = 0.51; large) (p <
      0.05). The quantification of match activity variables, particularly the total
      number of accelerations and decelerations and the number of sprints, provides
      insights into the fatigue status in elite soccer players 40 and 64 h post-match.

PMID- 29339990
TI  - High-Intensity Small-Sided Games versus Repeated Sprint Training in Junior Soccer
      Players.
AB  - The aim of this study was to compare the effects of high-intensity small-sided
      games training (SSGT) versus repeated-sprint training (RST) on repeated-sprint
      ability (RSA), soccer specific endurance performance and short passing ability
      among junior soccer players. The junior soccer players were recruited from of a
      professional team (age 16.9 +/- 1.1 years). The tests included the repeated
      shuttle-sprint ability test (RSSAT), Yo-Yo Intermittent Recovery Test level 1 (Yo
      Yo IR1) and Loughborough Soccer Passing Test (LSPT). Nineteen participants were
      randomly assigned to either the small-sided games training (SSGTG) (n = 10) or
      repeated-sprint training group (RSTG) (n = 9). Small-sided games or repeated
      sprint training were added to the regular training sessions for two days of the
      regular practice week. The Wilcoxon signed-rank and Mann-Whitney U tests were
      used to examine differences in groups and training effects. A time x training
      group effect was found in the improvement of short-passing ability for the
      smallsided games training group which showed significantly better scores than the
      repeated-sprint training group (p <= 0.05). Both groups showed similar
      improvements in RSAdecrement (p < 0.05). Only the repeated-sprint training group
      improved in the Yo-Yo IR1 (p < 0.05). This study clearly shows that high
      intensity small-sided games training can be used as an effective training mode to
      enhance both repeated sprint ability and short-passing ability.

PMID- 29339991
TI  - Multivariate Profiles of Selected versus Non-Selected Elite Youth Brazilian
      Soccer Players.
AB  - This study determined whether a multivariate profile more effectively
      discriminated selected than non-selected elite youth Brazilian soccer players.
      This examination was carried out on 66 youth soccer players (selected, n = 28,
      mean age 16.3 +/- 0.1; non-selected, n = 38, mean age 16.7 +/- 0.4) using
      objective instruments. Multivariate profiles were assessed through anthropometric
      characteristics, biological maturation, tactical-technical skills, and motor
      performance. The Student's t-test identified that selected players exhibited
      significantly higher values for height (t = 2.331, p = 0.02), lean body mass (t =
      2.441, p = 0.01), and maturity offset (t = 4.559, p < 0.001), as well as
      performed better in declarative tactical knowledge (t = 10.484, p < 0.001),
      shooting (t = 2.188, p = 0.03), dribbling (t = 5.914, p < 0.001), speed - 30 m (t
      = 8.304, p < 0.001), countermovement jump (t = 2.718, p = 0.008), and peak power
      tests (t = 2.454, p = 0.01). Forward stepwise discriminant function analysis
      showed that declarative tactical knowledge, running speed -30 m, maturity offset,
      dribbling, height, and peak power correctly classified 97% of the selected
      players. These findings may have implications for a highly efficient selection
      process with objective measures of youth players in soccer clubs.

PMID- 29339992
TI  - Effects of Passive and Active Rest on Physiological Responses and Time Motion
      Characteristics in Different Small Sided Soccer Games.
AB  - The purpose of this study was to investigate the effects of resting regimes on
      physiological responses and time motion characteristics between bouts during
      small sided games (SSGs) in young soccer players. Sixteen players (average age
      16.87 +/- 0.34 years; body height 176.69 +/- 3.21 cm; body mass 62.40 +/- 2.59
      kg; training experience 3.75 +/- 0.44 years) performed four bouts 2-a-side, 3-a
      side and 4-a-side games with three minutes active (SSGar: Running at 70% of
      HRmax) and passive (SSGpr) rest between bouts at two-day intervals. The heart
      rate (HR) along with total distance covered in different speed zones - walking
      (W, 0-6.9 km.h-1), low-intensity running (LIR, 7.0-12.9 km.h-1), moderate
      intensity running (MIR, 13.0-17.9 km.h-1) and high-intensity running (HIR,
      >18km.h-1), were monitored during all SSGs, whereas the rating of perceived
      exertion (RPE, CR-20) and venous blood lactate (La-) were determined at the end
      of the last bout of each SSG. The results demonstrated that all SSGpr elicited
      significantly higher physiological responses compared to SSGar in terms of the
      RPE and La- (p < 0.05). In addition, 2-a-side SSGpr induced significantly lower
      %HRmax responses and total distance covered than 2-a-side SSGar (p < 0.05).
      Moreover, the distance covered at HIR was significantly higher in 4-a-side SSGar
      than 4-side SSGpr. The results of this study indicate that both SSGs with passive
      and active rest can be used for soccer specific aerobic endurance training.
      Furthermore, all SSGs with active recovery should be performed in order to
      increase players and teams' performance capacity for subsequent bouts.

PMID- 29339993
TI  - Functional and Muscle-Size Effects of Flywheel Resistance Training with Eccentric
      Overload in Professional Handball Players.
AB  - The aim of the study was to analyse the effects of 6 week (15 sessions) flywheel
      resistance training with eccentric-overload (FRTEO) on different functional and
      anatomical variables in professional handball players. Twenty-nine athletes were
      recruited and randomly divided into two groups. The experimental group (EXP, n =
      15) carried out 15 sessions of FRTEO in the leg-press exercise, with 4 sets of 7
      repetitions at a maximum-concentric effort. The control group (CON, n = 14)
      performed the same number of training sessions including 4 sets of 7 maximum
      repetitions (7RM) using a weight-stack leg-press machine. The results which were
      measured included maximal dynamic strength (1RM), muscle power at different
      submaximal loads (PO), vertical jump height (CMJ and SJ), 20 m sprint time (20
      m), T-test time (T-test), and Vastus-Lateralis muscle (VL) thickness. The results
      of the EXP group showed a substantially better improvement (p < 0.05-0.001) in
      PO, CMJ, 20 m, T-test and VL, compared to the CON group. Moreover, athletes from
      the EXP group showed significant improvements concerning all the variables
      measured: 1RM (ES = 0.72), PO (ES = 0.42 - 0.83), CMJ (ES = 0.61), SJ (ES =
      0.54), 20 m (ES = 1.45), T-test (ES = 1.44), and VL (ES = 0.63 - 1.64). Since
      handball requires repeated short, explosive effort such as accelerations and
      decelerations during sprints with changes of direction, these results suggest
      that FRTEO affects functional and anatomical changes in a way which improves
      performance in well-trained professional handball players.

PMID- 29339994
TI  - The Second to Fourth Digit Ratio in Elite and Non-Elite Greco-Roman Wrestlers.
AB  - A low second-to-fourth digit ratio (2D:4D) has been reported to correlate with
      high performance and athletic potential of an individual in sport. It has been
      suggested that 2D:4D is a relatively weak predictor of strength and a stronger
      predictor of efficiency in aerobic exercise. Comparing extreme groups on a
      continuum of sports performance requiring high power (physical strength) output
      would be helpful to resolve this issue. Therefore, the purpose of the present
      study was to compare the 2D:4D ratio of world-class elite Greco-Roman wrestlers
      (n = 10) taking part in Olympic fitness camps in 2013 with the 2D:4D ratio of non
      elite collegiate wrestlers (n = 20), and age-matched sedentary males (n = 40).
      The 2D:4D ratios of elite wrestlers were lower compared to non-elite athletes (p
      < 0.01, right hand d = 1.70, left hand d = 1.67) and the control group (p <
      0.0001, right hand d = 3.16, left hand d = 2.00). No significant differences were
      noted among the groups for right - left 2D:4D. We concluded that 2D:4D may
      discriminate between non-elite and world-class wrestlers. We also suggest that a
      low 2D:4D ratio could be linked to performance potential in wrestlers. As such,
      2D:4D may provide additional information, which is valuable in determining the
      potential athleticism of an individual, when it is used in conjunction with other
      measures.

PMID- 29339995
TI  - Physical Performance and Anthropometric Characteristics of Male South African
      University Soccer Players.
AB  - Soccer is the most popular sport worldwide. Despite its global acclaim,
      scientific studies of soccer have tended to focus on tactics and techniques,
      thereby neglecting the physical and physiological profile of the players.
      Therefore, the purpose of this study was to examine physical and anthropometric
      characteristics of male South African university soccer players. Twenty-seven
      male soccer players aged 19 to 24 (mean age: 22.1 years; s = 1.5 years)
      volunteered to participate in the study. The results showed that goalkeepers
      (77.5 +/- 9.7 kg) and defenders (68.2 +/- 6.5 kg) were the heaviest compared to
      players in other playing positions. The goalkeepers also had the highest
      percentage of body fat (11.3 +/- 2.3%), in contrast to midfielders who had the
      lowest body fat content (9.1 +/- 0.9%). With regard to flexibility, defenders
      (45.1 +/- 4.9 cm) and midfielders (45.9 +/- 5.4 cm) performed better than
      goalkeepers (37.1 +/- 4.3 cm) and strikers (40.1 +/- 3.4 cm). Midfielders (57.2
      +/- 3.1 ml1.kg-1.min1) and defenders (56.1 +/- 5.1 ml1.kg-1.min1) had
      significantly higher values of maximal oxygen uptake (VO2max) than goalkeepers
      (47.9 +/- 0.2 ml-1.kg-1.min-1) and strikers (49.8 +/- 6.2 ml-1.kg-1.min-1). No
      significant (p > 0.05) differences were observed for all other variables, with
      the exception of body height, body mass, and VO2max. It was therefore concluded
      that sports scientists and coaches should tailor conditioning programmes in
      soccer according to players' positions in view of the implications for successful
      performance.

PMID- 29339996
TI  - Judging in Rhythmic Gymnastics at Different Levels of Performance.
AB  - This study aimed to analyse the quality of difficulty judging in rhythmic
      gymnastics, at different levels of performance. The sample consisted of 1152
      difficulty scores concerning 288 individual routines, performed in the World
      Championships in 2013. The data were analysed using the mean absolute judge
      deviation from the final difficulty score, a Cronbach's alpha coefficient and
      intra-class correlations, for consistency and reliability assessment. For
      validity assessment, mean deviations of judges' difficulty scores, the Kendall's
      coefficient of concordance W and ANOVA eta-squared values were calculated.
      Overall, the results in terms of consistency (Cronbach's alpha mostly above 0.90)
      and reliability (intra-class correlations for single and average measures above
      0.70 and 0.90, respectively) were satisfactory, in the first and third parts of
      the ranking on all apparatus. The medium level gymnasts, those in the second part
      of the ranking, had inferior reliability indices and highest score dispersion. In
      this part, the minimum of corrected item-total correlation of individual judges
      was 0.55, with most values well below, and the matrix for between-judge
      correlations identified remarkable inferior correlations. These findings suggest
      that the quality of difficulty judging in rhythmic gymnastics may be compromised
      at certain levels of performance. In future, special attention should be paid to
      the judging analysis of the medium level gymnasts, as well as the Code of Points
      applicability at this level.

PMID- 29339997
TI  - The Relative Age Effect on Soccer Players in Formative Stages with Different
      Sport Expertise Levels.
AB  - The Relative Age Effect (RAE) in sport has been targeted by many research
      studies. The objective of this study was to analyze, in amateur clubs, the RAE of
      soccer players, according to the sport expertise level of the team (e.g., A, B, C
      and subsequent) that they belong to within the same game category. 1,098 soccer
      players in formative stages took part in the study, with ages varying between 6
      and 18 years old (U8 to U19 categories). All of them were members of 4 Spanish
      federated clubs. The birth dates were classified into 4 quartiles (Q1 = Jan-Mar;
      Q2 = Apr-Jun; Q3 = Jul-Sept; Q4 = Oct-Dec)according to the team they belonged to.
      The results obtained in the chi-squared test and d value (effect size) revealed
      the existence of RAE in the teams with the highest expertise level, "A" (X2 =
      15.342, p = .002, d = 0.4473) and "B" (X2 = 10.905, p = .012, d = 0.3657).
      However, in the lower level teams, "C and subsequent", this effect was not
      observed. Present findings show that players born during the first months of the
      year tend to be selected to play in teams with a higher sport expertise level of
      each category, due to their physical maturity. Consequently, this causes
      differences in terms of the experience they accumulate and the motivation that
      this creates in these players.

PMID- 29339998
TI  - Planning Training Loads for the 400 M Hurdles in Three-Month Mesocycles using
      Artificial Neural Networks.
AB  - This paper presents a novel approach to planning training loads in hurdling using
      artificial neural networks. The neural models performed the task of generating
      loads for athletes' training for the 400 meters hurdles. All the models were
      calculated based on the training data of 21 Polish National Team hurdlers, aged
      22.25 +/- 1.96, competing between 1989 and 2012. The analysis included 144
      training plans that represented different stages in the annual training cycle.
      The main contribution of this paper is to develop neural models for planning
      training loads for the entire career of a typical hurdler. In the models, 29
      variables were used, where four characterized the runner and 25 described the
      training process. Two artificial neural networks were used: a multi-layer
      perceptron and a network with radial basis functions. To assess the quality of
      the models, the leave-one-out cross-validation method was used in which the
      Normalized Root Mean Squared Error was calculated. The analysis shows that the
      method generating the smallest error was the radial basis function network with
      nine neurons in the hidden layer. Most of the calculated training loads
      demonstrated a non-linear relationship across the entire competitive period. The
      resulting model can be used as a tool to assist a coach in planning training
      loads during a selected training period.

PMID- 29339999
TI  - Reliability and Usefulness of the 30-15 Intermittent Fitness Test in Male and
      Female Professional Futsal Players.
AB  - The purpose of this study was to determine the reliability and usefulness of the
      30-15 Intermittent Fitness Test (30-15IFT) in professional male and female futsal
      players. Thirteen male (24.4 +/- 5.6 years; 174.5 +/- 10.3 cm; 70.3 +/- 9.9 kg)
      and fourteen female (23.3 +/- 4.5 years; 165.8 +/- 6.2 cm; 61.7 +/- 5.5 kg)
      professional futsal players performed the 30-15IFT on two occasions, separated by
      5 days. Maximal intermittent running velocity (VIFT) and heart rate at exhaustion
      (HRpeak) data were collected for both tests. Reliability was assessed by the
      intraclass correlation coefficient (ICC), typical error (TE) expressed as a
      coefficient of variation (CV), and smallest worthwhile change (SWC). VIFT
      demonstrated very good reliability between sessions, both for male (ICC = 0.92)
      and female (ICC = 0.96) players. As the TE for VIFT and HRpeak was similar to the
      calculated SWC for both male and female players, the usefulness of the test was
      rated as "medium". A change in performance of at least 2 stages in male players,
      or a change of more than 1 stage in female players could be interpreted as a
      meaningful change in aerobic futsal fitness. The results of this study
      demonstrate that the 30-15IFT is both a reliable and useful test for male and
      female professional futsal players.

PMID- 29340000
TI  - Sprinting, Change of Direction Ability and Horizontal Jump Performance in Youth
      Runners According to Gender.
AB  - The purpose of the study was to assess straight sprinting, change of direction
      ability and horizontal jump performance in youth runners according to age and
      gender. Two hundred and fifty-five youth runners (116 boys and 139 girls)
      participated in this study. The athletes were divided according to their age into
      five groups: under 8 yr (U8), under 10 yr (U10), under 12 yr (U12), under 14 yr
      (U14) and under 16 yr (U16). Significant differences (p < 0.01) were found
      between U8 and U10 in the 5 m sprint (d = 1.22), 505 agility test (505, d =
      0.96), modified agility test (MAT, d = 1.43), horizontal countermovement jump
      (HCMJ, d = 1.06) and arm swing HCMJ (HCMJAS, d = 1.44); between U10 and U12 in
      the 505 (d = 0.39), MAT (d = 0.74), HCMJ (d = 0.96) and HCMJAS (d = 0.75); and
      between U12 and U14 in 5 m (d = 0.84), HCMJ (d = 0.88) and HCMJAS (d = 0.79).
      However, no significant differences (p > 0.05, d = 0.29-1.17) between U14 and U16
      were observed in any of the tests. With regard to age and gender, in U8 and U10
      groups there were no significant differences (p > 0.05, d = 0.02-0.76) between
      boys and girls in any test. However, in U12 and U14 groups, significant gender
      differences (p < 0.05, d = 0.85-1.24) were found in the MAT. Likewise, the boys
      obtained better results than girls in the horizontal jump tests (p < 0.05, d =
      1.01-1.26). After the classification by age, some differences were observed
      between both genders, depending on the fitness variable evaluated.

PMID- 29340001
TI  - Neuromuscular Control During the Bench Press Movement in an Elite Disabled and
      Able-Bodied Athlete.
AB  - The disabled population varies significantly in regard to physical fitness, what
      is conditioned by the damage to the locomotor system. Recently there has been an
      increased emphasis on the role of competitive sport in enhancing health and the
      quality of life of individuals with disability. One of the sport disciplines of
      Paralympics is the flat bench press. The bench press is one of the most popular
      resistance exercises used for the upper body in healthy individuals. It is used
      not only by powerlifters, but also by athletes in most strength-speed oriented
      sport disciplines. The objective of the study was to compare neuromuscular
      control for various external loads (from 60 to 100% 1RM) during the flat bench
      press performed by an elite able-bodied athlete and an athlete with lower limb
      disability. The research project is a case study of two elite bench press
      athletes with similar sport results: an able-bodied athlete (M.W., age 34 years,
      body mass 103 kg, body height 1.72 m, 1RM in the flat bench press 200 kg) and a
      disabled athlete (M.T., age 31 years, body mass 92 kg, body height 1.70 m, 1RM in
      the flat bench press 190 kg). The activity was recorded for four muscles:
      pectoralis major (PM), anterior deltoid (AD), as well as for the lateral and long
      heads of the triceps brachii (TBlat and TBlong). The T-test revealed
      statistically significant differences between peak activity of all the considered
      muscles (AD with p = 0.001; PM with p = 0.001; TBlat with p = 0.0021 and TBlong
      with p = 0.002) between the 2 athletes. The analysis of peak activity differences
      of M.W and M.T. in relation to the load revealed statistically significant
      differences for load changes between: 60 to 100% 1RM (p = 0.007), 70 to 100% 1RM
      (p = 0.016) and 80 to 100% 1RM (p = 0.032). The flat bench press performed
      without legs resting firmly on the ground leads to the increased engagement of
      upper body muscles and to their greater activation. Isolated initial positions
      can be used to generate greater engagement of muscle groups during the bench
      press exercise and evoke their higher activation.

PMID- 29340002
TI  - Performance Changes of Elite Paralympic Judo Athletes During a Paralympic Games
      Cycle: A Case Study with the Brazilian National Team.
AB  - The aim of this study was to describe the variations in power performance of
      elite Paralympic judo athletes across three consecutive training cycles of
      preparation for the ParaPan American Games, the World Championship and the
      Paralympic Games. Eleven Paralympic judokas from the Brazilian National team
      participated in this study. They were repeatedly assessed using squat and
      countermovement jumps, mean propulsive power (MPP) in the jump-squat (JS), the
      bench press and prone bench pull at several moments of the preparation. Training
      supervision based on the optimum power zone (range of loads where power
      production is maximized) was provided in the final cycle, prior to the Paralympic
      Games. Magnitude-based inference was used to compare the repeated measurements of
      power performance. Lower and upper limb muscle power gradually increased
      throughout the cycles; however, the best results in all exercises were observed
      prior to the Paralympic Games, during which the team won four silver medals. As
      an illustration, prior to participation in the Paralympic Games the MPP in the JS
      was likely to very likely higher than prior to the World Championship (effect
      size [ES] = 0.77) and ParaPan American Games (ES = 0.53), and in January and
      March 2016 (ES = 0.98 and 0.92, respectively; months preceding the Paralympic
      Games). Power performance assessments can provide information about the evolution
      of Paralympic judokas, and training at the optimum power zone seems to constitute
      an effective method to improve lower and upper limb power in these athletes.

PMID- 29340003
TI  - Sports Activity Following Cementless Metaphyseal Hip Joint Arthroplasty.
AB  - An adequate level of physical activity has a substantial effect on both mental
      and physical human health. Physical activity is largely dependent on the function
      of the musculoskeletal and articular system. One of the most frequent diseases of
      this system is degenerative joint disease. Due to the changing and more demanding
      lifestyles and patients' willingness to be involved in sports activity, the
      expectations of hip joint arthroplasty are becoming increasingly high.
      Alleviating pain ceases to be the only reason for which patients choose surgical
      interventions, while the expectations often include involvement in various
      sports. Only few studies contain recommendations concerning the frequency, type
      and intensity of sports activity which are acceptable after hip joint
      arthroplasty. The aim of the study was to evaluate function and physical activity
      of people following cementless short-stem hip joint arthroplasty in the
      observation of at least five years. The study group comprised 106 patients who
      underwent total hip arthroplasty due to degenerative joint diseases, chosen
      according to inclusion criteria. Patients underwent routine physical examinations
      following the Harris Hip Score protocol, responded to the UCLA scale and
      questionnaires concerning pre-surgical and current physical activity. Our results
      demonstrated that hip joint arthroplasty in people suffering from degenerative
      joint diseases has a beneficial effect on their level of functioning and physical
      activity. Although physical activity and the level of functioning obviously
      reduced as a person aged, the level of physical activity continued to be very
      high in both groups, with function of the hip joint evaluated as very good.

PMID- 29340004
TI  - Performance and Kinematic Differences in Putting between Healthy and Disabled
      Elite Golfers.
AB  - Golfers with disability are limited in the execution of the full golf swing, but
      their performance in putting may be comparable because this stroke does not
      demand significant strength, balance and range of motion. Therefore, the aim of
      this study was to compare putting performance, kinetic and kinematic consistency
      between golfers with different disabilities and healthy athletes. The
      participants consisted of three disabled athletes (perinatal cerebral palsy,
      multiple sclerosis, below knee lower limb amputee) and three healthy golfers (age
      34 +/- 4.5 years, body height 178 +/- 3.3 cm, body mass 83 +/- 6.2 kg). The
      golfers' movements were recorded by active 3D markers for kinematic analyses; the
      subjects performed 10 trials of a 6 m putting task while standing on separate
      force platforms placed under each lower limb. Putting performance was measured by
      the distance of the final ball position to the centre of the hole. ANOVA analyses
      did not show any differences in clubhead speed and total ball distance from the
      hole. The consistency of those two parameters expressed by the coefficient of
      variation (CV) was CV = 0.5% or better in both groups for clubhead speed and
      ranged from CV = 0.40 to 0.61% in healthy and CV = 0.21 to 0.55% in disabled
      athletes for total error distance. The main effect ANOVA showed differences in
      weight shift, hip and shoulder kinematics (p < 0.05) between healthy players and
      all players with disability. All disabled athletes shifted their weight toward
      the healthy side (towards the healthy lower limb) and alternated the end of the
      swing. The player with below knee amputation had the lowest range of motion in
      the shoulder joint during the putting stroke. The players with perinatal cerebral
      palsy and multiple sclerosis had the largest range of motion in the hips. Putting
      performance of disabled golfers was similar to healthy athletes. During training
      of disabled players, coaches should pay attention to the specificity of a
      particular disability when focused on putting performance. However, individual
      technique should achieve the same consistency as observed in healthy players.

PMID- 29340005
TI  - Comparison of Aerobic Performance Testing Protocols in Elite Male Wheelchair
      Basketball Players.
AB  - In wheelchair sports, aerobic performance is commonly assessed with the use of an
      arm crank ergometer (ACE), a wheelchair ergometer (WCE) or a wheelchair treadmill
      (WCT). There are different protocols to identify peak oxygen uptake in wheelchair
      sports; however, only a few protocols have been applied to evaluate these
      conditions in wheelchair basketball players. The purpose of this study was to
      compare physiological responses during maximal exercise testing with the use of
      ACE and WCT in wheelchair basketball players. Twelve elite male wheelchair
      basketball players participated in this study. The research was performed during
      a training camp of the Polish National Wheelchair Basketball Team. The study
      participants were divided into two functional categories: A (players with class
      1.0 - 2.5) and B (players with class 3.0 - 4.5). Two main maximal exercise tests,
      i.e. wheelchair treadmill stress test (WCT test) and arm crank ergometer stress
      test (ACE test) were used to evaluate aerobic performance of the players. There
      were no statistically significant differences in aerobic tests between the
      players from both groups. The comparison of results achieved in two aerobic tests
      performed on WCT and ACE did not reveal any significant differences between the
      analyzed variables (peak heart rate (HRpeak), peak oxygen uptake (VO2peak),
      minute ventilation (VE), anaerobic threshold (AT), lactate concentration
      (LApeak), and a drop in lactate concentration (%LA)). Strong correlations between
      results achieved in WCT and ACE tests were found for VO2peak, VE and LApeak. The
      main conclusion of the study is that both WCT and ACE tests may be useful when
      determining aerobic capacity of wheelchair basketball players. Moreover, both
      protocols can be used by athletes regardless of their functional capabilities and
      types of impairment.

PMID- 29340006
TI  - The Impact of the Progressive Efficiency Test on a Rowing Ergometer on White
      Blood Cells Distribution and Clinical Chemistry Changes in Paralympic Rowers
      During the Preparatory Stage Before the Paralympic Games in Rio, 2016 - A Case
      Report.
AB  - There is a large gap in knowledge regarding research on post-exercise blood
      changes in disabled athletes. There are relatively few data on adaptive
      mechanisms to exercise in disabled athletes, including disabled rowers. Two
      rowers from a Polish adaptive rowing settle TAMix2x that qualified for the
      Paralympic Games in Rio, 2016 took part in this study. They performed a
      progressive test on a rowing ergometer until exhaustion. The cardiorespiratory
      fitness measures, complete blood count, white blood cells' distribution and 30
      clinical chemistry variables describing laboratory diagnostic profiles and
      general health were determined. The extreme effort induced changes in all studied
      metabolites (glucose, creatinine, urea, uric acid, total and direct bilirubin),
      albumin, total protein levels in both participants. Furthermore, a post-exercise
      increase in aspartate transaminase activity, yet a 2-fold decrease during the
      recovery time in both rowers were found. White blood cell count increased 2-fold
      after the test. The percentages of natural killer cells were higher and total T
      lymphocytes were lower after the exercise protocol. There were higher percentages
      of suppressor/cytotoxic and lower percentages of helper/inducer T lymphocyte
      subsets in both studied rowers. No changes in B lymphocytes distribution were
      observed. Lack of inflammatory symptoms during the experiment suggests a high
      level of rowers' biological adaptation to the physical effort. The different
      changes in physiological, biochemical and immunological variables are related to
      the adaptive mechanism to physical exercise allowing for improvement of
      performance.

PMID- 29340008
TI  - Chemotherapy-induced metastasis in breast cancer.

PMID- 29340007
TI  - Genomic insights into Mycobacterium simiae human colonization.
AB  - Mycobacterium simiae (Karassova V, Weissfeiler J, Kraszanay E, Acta Microbiol
      Acad Sci Hung 12:275-82, 1965) is a slow-growing nontuberculous Mycobacterium
      species found in environmental niches, and recently evidenced as an opportunistic
      Human pathogen. We report here the genome of a clinical isolate of M. simiae
      (MsiGto) obtained from a patient in Guanajuato, Mexico. With a size of 6,684,413
      bp, the genomic sequence of strain MsiGto is the largest of the three M. simiae
      genomes reported to date. Gene prediction revealed 6409 CDSs in total, including
      6354 protein-coding genes and 52 RNA genes. Comparative genomic analysis
      identified shared features between strain MsiGto and the other two reported M.
      simiae genomes, as well as unique genes. Our data reveals that M. simiae MsiGto
      harbors virulence-related genes, such as arcD, ESAT-6, and those belonging to the
      antigen 85 complex and mce clusters, which may explain its successful transition
      to the human host. We expect the genome information of strain MsiGto will provide
      a better understanding of infective mechanisms and virulence of this emergent
      pathogen.

PMID- 29340009
TI  - What is changing in the adjuvant treatment of melanoma?

PMID- 29340010
TI  - Elongation vs stalling: place your BET.

PMID- 29340011
TI  - Capecitabine for primary breast cancer.

PMID- 29340012
TI  - Biomarkers in colorectal cancer screening.

PMID- 29340013
TI  - The small molecule SI113 synergizes with mitotic spindle poisons in arresting the
      growth of human glioblastoma multiforme.
AB  - Glioblastoma multiforme (GBM) is the deadliest brain tumor. State-of-art GBM
      therapy often fails to ensure control of a disease characterized by high
      frequency of recurrences and progression. In search for novel therapeutic
      approaches, we assayed the effect of compounds from a cancer drug library on the
      ADF GBM cell line, establishing their elevated sensitivity to mitotic spindle
      poisons. Our previous work showed that the effectiveness of the spindle poison
      paclitaxel in inhibiting cancer cell growth was dependent on the expression of
      RANBP1, a regulatory target of the serine/threonine kinase SGK1. Recently, we
      developed the small molecule SI113 to inhibit SGK1 activity. Therefore, we
      explored the outcome of the association between SI113 and selected spindle
      poisons, finding that these drugs generated a synergistic cytotoxic effect in GBM
      cells, drastically reducing their viability and clonogenic capabilities in vitro,
      as well as inhibiting tumor growth in vivo. We also defined the molecular bases
      of such a synergistic effect. Because SI113 displays low systemic toxicity, yet
      strong activity in potentiating the effect of radiotherapy in GBM cells, we
      believe that this drug could be a strong candidate for clinical trials, with the
      aim to add it to the current GBM therapeutic approaches.

PMID- 29340014
TI  - Cymbopogon citratus and Camellia sinensis extracts selectively induce apoptosis
      in cancer cells and reduce growth of lymphoma xenografts in vivo.
AB  - Cancer cells are reported to have elevated levels of reactive oxygen species
      (ROS) and are highly dependent on cellular defense mechanisms against oxidative
      stress. Numerous nutraceuticals and natural polyphenolic compounds have a wide
      range of abilities to alter cellular redox states with potential implications in
      various diseases. Furthermore, therapeutic options for cancers are mostly
      nonselective treatments including genotoxic or tubulin-targeting compounds. Some
      of the natural extracts, containing multiple bioactive compounds, could target
      multiple pathways in cancer cells to selectively induce cell death. Cymbopogon
      citratus (lemongrass) and Camellia sinensis (white tea) extracts have been shown
      to have medicinal properties, however, their activity against lymphoma and
      leukemia, as well as mechanistic details, have not been fully characterized.
      Herein, we report potent anti-cancer properties in dose and time-dependent
      manners of ethanolic lemongrass and hot water white tea extracts in lymphoma and
      leukemia models. Both extracts were able to effectively induce apoptosis
      selectively in these human cancer cell types. Interestingly, ethanolic lemongrass
      extract induces apoptosis primarily by the extrinsic pathway and was found to be
      dependent on the generation of ROS. Conversely, apoptotic induction by hot water
      white tea extract was independent of ROS. Furthermore, both of these extracts
      caused mitochondrial depolarization and decreased rates of oxygen consumption in
      lymphoma and leukemia cells, leading to cell death. Most importantly, both these
      extracts were effective in reducing tumor growth in human lymphoma xenograft
      models when administered orally. Thus, these natural extracts could have
      potential for being nontoxic alternatives for the treatment of cancer.

PMID- 29340015
TI  - Apatinib alone or combined with radiotherapy in metastatic prostate cancer:
      Results from a pilot, multicenter study.
AB  - Background: To study safety and efficacy of apatinib in combination of
      radiotherapy in patients with symptomatic bony disease prostate cancer(SBPC),
      based on the potential synergistic antitumor activity between apatinib and
      Radiation Therapy (RT). Patients and methods: In phase I dose escalation part, 18
      patients received apatinib dose at 250 mg every other day, 250 mg daily and 500
      mg daily. In phase II part, the 250 mg daily cohorts were expanded to 20 patients
      in combination of RT (6 Gy/fraction, 5 fraction in total), one patient lost
      followed up and excluded the study, comparing with RT alone cohort with 10
      patients, ratio of RT to RT + apatinib was 1 to 2. Evaluations included adverse
      events (AEs), prostate specific antigen (PSA) changes, radiographic evaluation
      and pain relief. Results: In phase I study, common apatinib-related AEs (arAEs)
      were fatigue, anorexia, hand foot syndrome, proteinuria, and hypertension (HTN).
      Grade 3arAEs included HTN, proteinuria, liver dysfunction. In phase II study,
      combination apatinib with RT cohorts, AEs events increased comparing with either
      apatinib alone or RT alone; at the same time, combination cohorts showed PSA
      declines of >=50% in 12 patients, and stable disease in 6 patients. Combination
      cohorts had pain control significantly improved in both level and duration
      comparing with RT alone. Conclusions: In SBPC patients, apatinib at less than 500
      mg daily dose as mono-therapy had tolerable toxicity. Apatinib at dose of 250 mg
      daily in combining with RT synergized pain control, the overall AEs were
      manageable. Further studies are needed in large sample size future trials.

PMID- 29340016
TI  - MiR-19 regulates the proliferation and invasion of glioma by RUNX3 via beta
      catenin/Tcf-4 signaling.
AB  - Accumulating data demonstrates that the network dysregulation of microRNA
      medicated target genes is involved in glioma. We have previously found miR-19a/b
      overexpression in glioma cell lines and specimens with various tumour grades.
      However, there was no report on the function and regulatory mechanism of miR
      19a/b in glioma. In this study, based on our previous research data, we first
      determine the inverse relationship between miR-19 (miR-19a and miR-19b) and RUNX3
      which is also identified the reduced expression in tumour tissues by real-time
      PCR and IHC. Luciferase reporter assay and western blot analysis revealed that
      RUNX3 was a direct target of miR-19. Down-regulation of miR-19 dramatically
      inhibited proliferation, invasion and induced the cell cycle G1 arrest and
      apoptosis, at least partly via the up-regulation of RUNX3. Furthermore,
      Mechanistic investigation indicated that knockdown of miR-19 repressed the beta
      catenin/TCF4 transcription activity. In conclusion, our study validates a
      pathogenetic role of miR-19 in glioma and establishes a potentially regulatory
      and signaling involving miR-19 /RUNX3/beta-catenin, also suggesting miR-19 may be
      a candidate therapeutic target in glioma.

PMID- 29340017
TI  - Altered GNAS imprinting due to folic acid deficiency contributes to poor embryo
      development and may lead to neural tube defects.
AB  - Disturbed epigenetic modifications have been linked to the pathogenesis of Neural
      Tube Defects (NTDs) in those with folate deficiency during pregnancy. However,
      evidence is lacking to delineate the critical region in epigenome regulated by
      parental folic acid and mechanisms by which folate deficiency affects normal
      embryogenesis. Our data from clinical samples revealed the presence of aberrant
      DNA methylation in GNAS imprinting cluster in NTD samples with low folate
      concentrations. Results from mouse models indicated that the establishment of
      GNAS imprinting was influenced by both maternal and paternal folate-deficient
      diets. Such aberrant GNAS imprinting was present prior to the gametogenesis
      period. Imprinting in Exon1A/GNAS gDMR was abolished in both spermatozoa and
      oocytes upon treating with a parental folate-deficient diet (3.6% in spermatozoa,
      9.8% in oocytes). Interestingly, loss of imprinting in the GNAS gene cluster
      altered chromatin structure to an overwhelmingly open structure (58.48% in the
      folate-free medium group vs. 39.51% in the folate-normal medium group; P < 0.05),
      and led to a disturbed expression of genes in this region. Furthermore, an
      elevated cyclic AMP levels was observed in folate acid deficiency group. Our
      results imply that GNAS imprinting plays major roles in folic acid metabolism
      regulation during embryogenesis. Aberrant GNAS imprinting is an attribute to
      NTDs, providing a new perspective for explaining the molecular mechanisms by
      which folate supplementation in human pregnancy provides protection from NTDs.

PMID- 29340018
TI  - Survival prediction of kidney renal papillary cell carcinoma by comprehensive
      LncRNA characterization.
AB  - Kidney renal papillary cell carcinoma (KIRP) accounts for 10%-15% of renal cell
      carcinoma (RCC), patients with KIRP tend to have a poor prognosis, and there was
      a lack of effective prognostic indicators for this type of cancer. Currently,
      owing to the availability of The Cancer Genome Atlas (TCGA), long non-coding RNAs
      (LncRNAs) have been discovered to indicate a prognostic value in some tumors. In
      that regard, we analyzed lncRNA-sequencing data of KIRP in TCGA, and among 780
      differentially-expressed lncRNAs, we selected 37 lncRNAs which were able to
      assist the prognosis. In addition, by using the multivariate cox regression
      analysis, the prognosis index (PI) that consisted of 7 lncRNAs (including AFAP1
      AS1, GAS6-AS1, RP11-1C8.7, RP11-21L19.1, RP11-503C24.1, RP11-536I6.2, and RP11
      63A11.1) could predict the progression and outcomes of KIRP with accuracy. More
      importantly, the PI was considered an independent indicator for prognostication
      of KIRP. Moreover, having categorized patients with KIRP into cohorts of high
      risk and low risk, according to the PI, we found that the key genes and pathways
      varied in these two groups. Overall, these LncRNAs, especially the PI, may be
      conceived as biomarkers and helpful for determining the different pathological
      stages for KIRP patients. However, their biological functions need to be further
      confirmed.

PMID- 29340019
TI  - Yonsei criteria: a clinical reflection of stage I left-sided pancreatic cancer.
AB  - In this study, we examined associations between pancreatic cancer that met the
      Yonsei criteria (YC) and classifications from the 8th edition of the American
      Joint Committee on Cancer (AJCC) staging system. Clinicopathological and survival
      data were collected from132 patients who underwent distal pancreatectomy for left
      sided pancreatic ductal adenocarcinoma between January 2000 and December 2015,
      and the utility of the YC for selecting treatment and predicting survival was
      evaluated using the 8th AJCC staging manual. Of the 102 patients who ultimately
      qualified for the study, 45 patients were reclassified as stage I based on the
      8th AJCC cancer staging system. Disease-free survival and disease-specific
      survival periods were longer in stage I patients who met the YC than in those who
      did not. Clinicopathological characteristics did not differ between stage I
      patients who did and did not meet the YC. These results suggest that meeting the
      YC criteria may be a clinical indicator that left-sided pancreatic cancer
      patients who are candidates for resection have early-stage disease according to
      the 8th edition of the AJCC staging manual.

PMID- 29340020
TI  - EYA2 promotes lung cancer cell proliferation by downregulating the expression of
      PTEN.
AB  - Lung cancer is the leading cause of cancer-related death worldwide. Despite
      advances have been made in diagnosis and therapeutic strategies, the prognosis of
      lung cancer is still very poor. Eyes absent transcriptional cofactor EYA2 has
      been shown to promote lung cancer cell growth, however, the underlying molecular
      mechanism is still not fully understood. In the present study, we found that EYA2
      was up-regulated in lung cancer, and EYA2 led to increased cell proliferation by
      inhibiting Phosphatase and tensin homologue (PTEN) expression via modulation of
      miR-93. Additionally, survival analysis showed that lung cancer patients with
      higher EYA2 expression predicted a worse prognosis. Therefore, these findings
      demonstrate that EYA2 may play an important role in lung cancer occurrence and
      progression. Targeting EYA2 may provide a feasible approach in developing novel
      anticancer therapeutics.

PMID- 29340022
TI  - A functional polymorphism of SSBP1 gene predicts prognosis and response to
      chemotherapy in resected gastric cancer patients.
AB  - Growing evidence has indicated that single-stranded DNA-binding proteins 1
      (SSBP1) is involved in tumor initiation and progression. However, effects of
      single nucleotide polymorphisms (SNPs) in SSBP1 gene on gastric cancer (GC)
      prognosis are still unknown. In present study, two functional SNPs from SSBP1
      were selected and genotyped in a large cohorts of 1030 resected GC patients (326
      in the training set, 704 in the validation set) to explore the association of
      SNPs with patients' survival. The rs6976500 G allele (CG/GG) genotypes were found
      significantly associated with both worse overall survival (OS) and recurrence
      free survival (RFS) in the training and the independent validation set when
      compared to C allele genotype, which reaching a more robust statistical
      significance in the pooled analysis. Furthermore, integration of rs6976500
      genotypes and TNM stage significantly improved the prognosis prediction models
      based on TNM stage alone. In addition, only carriers with at least one G allele
      of rs6976500 gained significant survival benefit from FOLFOX-based ACT.
      Mechanistically, SNP rs6976500 G allele genotype could significantly decrease
      promoter transcriptional activity and markedly reduce expression level of SSBP1
      compared with the C allele genotype in GC cells. This was further substantiated
      by immunohistochemical assay in 70 GC tissue samples. Our study presents the
      first evidence that SNP rs6976500 G allele genotypes might contribute to GC
      prognosis by attenuating SSBP1 promoter activity and gene expression, and
      provides the guidance in refining therapeutic decisions of GC patients. Further
      exploration on its function is needed to clarify the exact biological mechanism
      behind.

PMID- 29340023
TI  - Role and regulation of Yap in KrasG12D-induced lung cancer.
AB  - The Hippo pathway and its downstream transcriptional co-activator Yap influence
      lung cancer, but the nature of the Yap contribution has been unclear. Using a
      genetically engineered mouse lung cancer model, we show that Yap deletion
      completely blocks KrasG12D and p53 loss-driven adenocarcinoma initiation and
      progression, whereas heterozygosity for Yap partially suppresses lung cancer
      growth and progression. We also characterize Yap expression during tumor
      progression and find that nuclear Yap can be detected from the earliest stages of
      lung carcinogenesis, but at levels comparable to that in aveolar type II cells,
      which are a cell of origin for lung adenocarcinoma. At later stages of
      tumorigenesis, variations in Yap levels are detected, which correlate with
      differences in cell proliferation within tumors. Our observations imply that Yap
      is not directly activated by oncogenic Kras during lung tumorigenesis, but is
      nonetheless absolutely required for this tumorigenesis, and support Yap as a
      therapeutic target in lung adenocarcinoma.

PMID- 29340021
TI  - A novel messenger RNA signature as a prognostic biomarker for predicting relapse
      in pancreatic ductal adenocarcinoma.
AB  - Pancreatic ductal adenocarcinoma (PDAC) death rate and recurrence rate have
      remained obstinately high. Current methods can not satisfy the need of predicting
      cancer relapse accurately. Utilizing expression profiles of 10 GEO datasets (N =
      774), we identified 154 differentially expressed genes (DEGs) between PDAC and
      normal pancreas tissue or paracancerous tissue. Next we built a 16-mRNA-based
      signature by means of the LASSO COX regression model. We also validated the
      prognostic value of the signature. Patients were classified into high-risk and
      low-risk group according to the signature risk score; 1 year RFS was 45% (95% CI:
      31.6%-63.9%) for high-risk group in contrast to 92.5% (95% CI: 86.3%-99.1%) for
      low-risk group. Moreover, it could predict RFS well in cases with the receipt of
      different treatment modalities. The 16-mRNA-based signature was an independent
      and powerful prognostic biomarker for RFS for PDAC patients (HR = 7.74, 95% CI:
      3.25-18.45, p < 0.0001).

PMID- 29340024
TI  - Chitosan composite scaffold combined with bone marrow-derived mesenchymal stem
      cells for bone regeneration: in vitro and in vivo evaluation.
AB  - The study aimed to develop a chitosan (CS)-based scaffold for repairing calvarial
      bone defects. We fabricated composite scaffolds made of CS and bovine-derived
      xenograft (BDX), characterized their physicochemical properties including pore
      size and porosity, absorption, degradation, and compressive strength, compared
      their efficacy to support in vitro proliferation and differentiation of human jaw
      bone marrow-derived mesenchymal stem cells (hJBMMSCs), and evaluated their bone
      regeneration capacity in critical-size rat calvarial defects. The CS/BDX (mass
      ratio of 40:60) composite scaffold with porosity of 46.23% and pore size of 98.23
      MUm exhibited significantly enhanced compressive strength than the CS scaffold
      (59.33 +/- 4.29 vs. 18.82 +/- 2.49 Kpa). The CS/BDX (40:60) scaffold induced
      better cell attachment and promoted more osteogenic differentiation of hJBMMSCs
      than the CS scaffold. The CS/BDX (40:60) scaffold seeded with hJBMMSCs was the
      most effective in supporting new bone formation, as evidenced by better
      histomorphometry results, larger new bone area, and more obvious mature lamellar
      bone formation compared to other groups in rat calvarial defects 8 weeks after
      implantation. These results suggest that CS/BDX composite scaffold combining with
      hJBMMSCs has the potential for bone defect regeneration.

PMID- 29340025
TI  - The novel ATM inhibitor (AZ31) enhances antitumor activity in patient derived
      xenografts that are resistant to irinotecan monotherapy.
AB  - Irinotecan, a standard of care therapy for CRC, elicits cytotoxic effects by
      generating double strand breaks resulting in DNA damage. The activation of the
      ATM pathway plays a fundamental role in regulating the cellular response and
      repair to DNA damage. The objective of this preclinical study was to determine
      whether ATM inhibition would enhance sensitivity to irinotecan treatment.
      Treatment effects of AZ31, irinotecan or AZ31 + irinotecan were investigated in
      CRC cell lines and CRC patient derived xenografts. Activation of ATM and
      downstream targets p-RAD50 and p-H2AX were evaluated by immunohistochemistry.
      Combinational effects were demonstrated in 4 out of 8 CRC explants.
      Interestingly, each of the combinational sensitive CRC PDX models were shown to
      be more resistant to irinotecan single agent therapy. Treatment with irinotecan
      significantly elevated the ATM pathway evident by an increase in the activation
      of H2AX and RAD50. Combinational therapy reduced the activation of H2AX and RAD50
      when compared to irinotecan alone in the combination sensitive CRC098. AZ31 +
      irinotecan was effective at reducing tumor growth in tumors that exhibited
      resistance to irinotecan in our CRC PDX model. These findings support further
      investigation of this combinational therapy for the treatment of CRC patients.

PMID- 29340026
TI  - Evaluating the bias of circRNA predictions from total RNA-Seq data.
AB  - CircRNAs are a group of endogenous noncoding RNAs. The quickly developing high
      throughput RNA sequencing technologies along with novel bioinformatics approaches
      have enabled researchers to systematically identify circRNAs and their biological
      functions in cells. Deep sequencing of rRNA-depleted RNAs treated with RNase R,
      which digests linear RNAs and leaves circRNAs enriched, is an efficient way to
      identify circRNAs. However, very few of RNase R treated data are at hand but a
      large amount of total RNA-Seq data with no sequencing costs is available, for
      circRNA predictions. In this study, we systematically investigated the prediction
      bias from total RNA-Seq data as well as the influence of sequencing depth,
      sequencing quality and single-end or paired-end sequencing strategy on the
      predictions. We also identified circRNA properties that may contribute to the
      improved prediction performance. Our analysis shows that circRNA predictions from
      total RNA-Seq data gain ~50% true positive. Sequencing error dramatically worsens
      the predictions, rather than single-end sequencing strategy or low sequencing
      depth. However, false positive can be carefully controlled by using data with
      good quality and narrowing down circRNAs guided by their properties.

PMID- 29340027
TI  - Dual SIRT1 expression patterns strongly suggests its bivalent role in human
      breast cancer.
AB  - Breast cancer is the most common cancer in women, and the leading cause of cancer
      death in women worldwide. SIRT1 (silent mating type information regulation 2
      homolog) 1 is a class-III histone deacetylase involved in apoptosis regulation,
      DNA repair and tumorigenesis. However, its role in breast carcinoma remains
      controversial, as both tumor-suppressive and tumor-promoting functions have been
      reported. Also, there are very few reports available where expression of SIRT1 is
      comprehensively analyzed in breast tumors classified by molecular subtype. Here,
      using a cohort of 50 human breast tumors and their matched normal tissues, we
      investigated SIRT1 expression levels in the 5 molecular subtypes of breast cancer
      according to the St Gallen classification (2013). Tumors and their corresponding
      normal tissue samples were collected from all patients, and SIRT1 mRNA and
      protein expression levels were then examined by real-time quantitative polymerase
      chain reaction and immunoblotting, respectively. After statistical analysis, the
      results showed a dual expression profile of SIRT1 in human breast carcinoma, with
      significant overexpression in luminal and HER2-enriched subtypes and
      significantly reduced expression in the triple-negative subtype. We also found an
      inverse correlation between SIRT1 expression and breast cancer aggressivity.
      These novel findings suggest that SIRT1 plays a dual role in breast tumors
      depending on its expression rate and the molecular subtype of the cancer. Our
      data also point to a potential role for SIRT1 as a prognostic biomarker in breast
      cancer.

PMID- 29340029
TI  - Selenium suppresses inflammation by inducing microRNA-146a in Staphylococcus
      aureus-infected mouse mastitis model.
AB  - We studied the effects of selenium (Se) on the inflammatory response in
      Staphylococcus aureus (S. aureus)-infected mastitis-model mice and mammary
      epithelial cells. In infected mice, Se elicited a dose-dependent decrease in
      mammary gland pathology that included inflammatory cell infiltration,
      disorganized acinar structure and mammary cell necrosis. Se decreased
      inflammation by increasing miR-146a and decreasing TLR2/6 as well as NF-kappaB
      and MAPK signaling pathways in mammary tissue from infected mice and mammary
      epithelial cells. A miR-146a inhibitor suppressed the anti-inflammatory effects
      of Se in infected mammary epithelial cells. Se, miR-146a and TLR2 were associated
      in determining the inflammatory response in mouse with infection-induced
      mastitis. Thus, Se inhibits pro-inflammatory responses in mammary tissues from S.
      aureus-infected mice by inducing miR-146a.

PMID- 29340028
TI  - High-resolution microbiome profiling uncovers Fusobacterium nucleatum,
      Lactobacillus gasseri/johnsonii, and Lactobacillus vaginalis associated to oral
      and oropharyngeal cancer in saliva from HPV positive and HPV negative patients
      treated with surgery and chemo-radiation.
AB  - Microbiome studies show altered microbiota in head and neck squamous cell
      carcinoma (HNSCC), both in terms of taxonomic composition and metabolic capacity.
      These studies utilized a traditional bioinformatics methodology, which allows for
      accurate taxonomic assignment down to the genus level, but cannot accurately
      resolve species level membership. We applied Resphera Insight, a high-resolution
      methodology for 16S rRNA taxonomic assignment that is able to provide species
      level context in its assignments of 16S rRNA next generation sequencing (NGS)
      data. Resphera Insight applied to saliva samples from HNSCC patients and healthy
      controls led to the discovery that a subset of HNSCC saliva samples is
      significantly enriched with commensal species from the vaginal flora, including
      Lactobacillus gasseri/johnsonii (710x higher in saliva) and Lactobacillus
      vaginalis (52x higher in saliva). These species were not observed in normal
      saliva from Johns Hopkins patients, nor in 16S rRNA NGS saliva samples from the
      Human Microbiome Project (HMP). Interestingly, both species were only observed in
      saliva from Human Papilloma Virus (HPV) positive and HPV negative oropharyngeal
      cancer patients. We confirmed the representation of both species in HMP data
      obtained from mid-vagina (n=128) and vaginal introitus (n=121) samples. Resphera
      Insight also led to the discovery that Fusobacterium nucleatum, an oral cavity
      flora commensal bacterium linked to colon cancer, is enriched (600x higher) in
      saliva from a subset of HNSCC patients with advanced tumors stages. Together,
      these high-resolution analyses on 583 samples suggest a possible role for
      bacterial species in the therapeutic outcome of HPV positive and HPV negative
      HNSCC patients.

PMID- 29340031
TI  - Analyzing the influence of kinase inhibitors on DNA repair by differential
      proteomics of chromatin-interacting proteins and nuclear phospho-proteins.
AB  - The combination of radiotherapy and pharmacological inhibition of cellular signal
      transduction pathways offers promising strategies for enhanced cancer cell
      inactivation. However, the molecular effects of kinase inhibitors especially on
      DNA damage detection and repair after X-irradiation have to be understood to
      facilitate the development of efficient and personalized treatment regimens.
      Therefore, we applied differential proteomics for analyzing inhibitor-induced
      changes in either chromatin-bound or phosphorylated nuclear proteins. The effect
      of the multi kinase inhibitor sorafenib on DNA repair, chromatin binding and
      phosphorylation of nuclear proteins was analyzed in UT-SCC 42B head and neck
      cancer cells using metabolic labeling based differential proteomics (SILAC).
      Sorafenib significantly inhibited DNA repair but failed to significantly affect
      chromatin interactions of 90 quantified proteins. In contrast, analyzing nuclear
      phospho-proteins following sorafenib treatment, we detected quantitative changes
      in 9 out of 59 proteins, including DNA-repair proteins. In conclusion, the
      analysis of nuclear phospho-proteins by differential proteomics is an effective
      tool for determining the molecular effects of kinase inhibitors on X-irradiated
      cells. Analyzing chromatin binding might be less promising.

PMID- 29340030
TI  - Increased efficacy of metformin corresponds to differential metabolic effects in
      the ovarian tumors from obese versus lean mice.
AB  - Obesity is a significant risk factor for ovarian cancer (OC) and associated with
      worse outcomes for this disease. We assessed the anti-tumorigenic effects of
      metformin in human OC cell lines and a genetically engineered mouse model of high
      grade serous OC under obese and lean conditions. Metformin potently inhibited
      growth in a dose-dependent manner in all four human OC cell lines through
      AMPK/mTOR pathways. Treatment with metformin resulted in G1 arrest, induction of
      apoptosis, reduction of invasion and decreased hTERT expression. In the K18
      gT121+/-; p53fl/fl; Brca1fl/fl (KpB) mouse model, metformin inhibited tumor
      growth in both lean and obese mice. However, in the obese mice, metformin
      decreased tumor growth by 60%, whereas tumor growth was only decreased by 32% in
      the lean mice (p=0.003) compared to vehicle-treated mice. The ovarian tumors from
      obese mice had evidence of impaired mitochondrial complex 2 function and energy
      supplied by omega fatty acid oxidation rather than glycolysis as compared to lean
      mice, as assessed by metabolomic profiling. The improved efficacy of metformin in
      obesity corresponded with inhibition of mitochondrial complex 1 and fatty acid
      oxidation, and stimulation of glycolysis in only the OCs of obese versus lean
      mice. In conclusion, metformin had anti-tumorigenic effects in OC cell lines and
      the KpB OC pre-clinical mouse model, with increased efficacy in obese versus lean
      mice. Detected metabolic changes may underlie why ovarian tumors in obese mice
      have heightened susceptibility to metformin.

PMID- 29340032
TI  - C3G promotes a selective release of angiogenic factors from activated mouse
      platelets to regulate angiogenesis and tumor metastasis.
AB  - Previous observations indicated that C3G (RAPGEF1) promotes alpha-granule
      release, evidenced by the increase in P-selectin exposure on the platelet surface
      following its activation. The goal of the present study is to further
      characterize the potential function of C3G as a modulator of the platelet
      releasate and its implication in the regulation of angiogenesis. Proteomic
      analysis revealed a decreased secretion of anti-angiogenic factors from activated
      transgenic C3G and C3G?Cat platelets. Accordingly, the secretome from both
      transgenic platelets had an overall pro-angiogenic effect as evidenced by an in
      vitro capillary-tube formation assay with HUVECs (human umbilical vein
      endothelial cells) and by two in vivo models of heterotopic tumor growth. In
      addition, transgenic C3G expression in platelets greatly increased mouse melanoma
      cells metastasis. Moreover, immunofluorescence microscopy showed that the pro
      angiogenic factors VEGF and bFGF were partially retained into alpha-granules in
      thrombin- and ADP-activated mouse platelets from both, C3G and C3GDeltaCat
      transgenic mice. The observed interaction between C3G and Vesicle-associated
      membrane protein (Vamp)-7 could explain these results. Concomitantly, increased
      platelet spreading in both transgenic platelets upon thrombin activation supports
      this novel function of C3G in alpha-granule exocytosis. Collectively, our data
      point out to the co-existence of Rap1GEF-dependent and independent mechanisms
      mediating C3G effects on platelet secretion, which regulates pathological
      angiogenesis in tumors and other contexts. The results herein support an
      important role for platelet C3G in angiogenesis and metastasis.

PMID- 29340033
TI  - CXCR4-expressing Mist1+ progenitors in the gastric antrum contribute to gastric
      cancer development.
AB  - Mist1 was recently shown to identify a discrete population of stem cells within
      the isthmus of the oxyntic gland within the gastric corpus. Chief cells at the
      base of the gastric corpus also express Mist1. The relevance of Mist1 expression
      as a marker of specific cell populations within the antral glands of the distal
      stomach, however, is unknown. Using Mist1-CreERT mice, we revealed that Mist1+
      antral cells, distinct from the Mist1+ population in the corpus, comprise long
      lived progenitors that reside within the antral isthmus above Lgr5+ or CCK2R+
      cells. Mist1+ antral progenitors can serve as an origin of antral tumors induced
      by loss of Apc or MNU treatment. Mist1+ antral progenitors, as well as other
      antral stem/progenitor population, express Cxcr4, and are located in close
      proximity to Cxcl12 (the Cxcr4 ligand)-expressing endothelium. During antral
      carcinogenesis, there is an expansion of Cxcr4+ epithelial cells as well as the
      Cxcl12+ perivascular niche. Deletion of Cxcl12 in endothelial cells or
      pharmacological blockade of Cxcr4 inhibits antral tumor growth. Cxcl12/Cxcr4
      signaling may be a potential therapeutic target.

PMID- 29340034
TI  - Prexasertib, a cell cycle checkpoint kinases 1 and 2 inhibitor, increases in
      vitro toxicity of PARP inhibition by preventing Rad51 foci formation in BRCA wild
      type high-grade serous ovarian cancer.
AB  - PARP inhibitors (PARPi) have been effective in high-grade serous ovarian cancer
      (HGSOC), although clinical activity is limited against BRCA wild type HGSOC. The
      nearly universal loss of normal p53 regulation in HGSOCs causes dysfunction in
      the G1/S checkpoint, making tumor cells reliant on Chk1-mediated G2/M cell cycle
      arrest for DNA repair. Therefore, Chk1 is a reasonable target for a combination
      strategy with PARPi in treating BRCA wild type HGSOC. Here we investigated the
      combination of prexasertib mesylate monohydrate (LY2606368), a Chk1 and Chk2
      inhibitor, and a PARP inhibitor, olaparib, in HGSOC cell lines (OVCAR3, OV90,
      PEO1 and PEO4) using clinically attainable concentrations. Our findings showed
      combination treatment synergistically decreased cell viability in all cell lines
      and induced greater DNA damage and apoptosis than the control and/or
      monotherapies (p<0.05). Treatment with olaparib in BRCA wild type HGSOC cells
      caused formation of Rad51 foci, whereas the combination treatment with
      prexasertib inhibited transnuclear localization of Rad51, a key protein in
      homologous recombination repair. Overall, our data provide evidence that
      prexasertib and olaparib combination resulted in synergistic cytotoxic effects
      against BRCA wild type HGSOC cells through reduced Rad51 foci formation and
      greater induction of apoptosis. This may be a novel therapeutic strategy for
      HGSOC.

PMID- 29340035
TI  - ABCB1 3435TT and ABCG2 421CC genotypes were significantly associated with longer
      progression-free survival in Chinese breast cancer patients.
AB  - Objective: To investigate the distribution of ABCB1 C3435T and ABCG2 C421A gene
      polymorphisms in Chinese Han population and their influences on the
      susceptibility and prognosis of breast carcinoma. Methods: A total of 200 female
      subjects were enrolled in this study, comprising 100 breast cancer patients and
      100 healthy controls. Carcinoma and para-carcinoma tissues were collected from
      the breast cancer patients, while peripheral blood was collected from healthy
      controls. Single nucleotide polymorphisms (SNPs) were detected by the Taqman
      method. Progression-free survival (PFS) and 5-year survival rate of the patients
      were calculated. Results: ABCB1 C3435T and ABCG2 C421A polymorphisms were not
      associated with disease susceptibility and 5-year survival rate in the study
      population (p>0.05). However, a high mutation rate of both ABCB1 C3435T and ABCG2
      C421A (16% and 17%, respectively) was observed in breast cancer tissues. Patients
      with ABCB1 3435TT genotype or ABCG2 421CC genotype had longer PFS (p<0.05).
      Conclusion: ABCB1 3435TT and ABCG2 421CC were significantly associated with
      longer PFS in Chinese breast cancer patients.

PMID- 29340036
TI  - The association between elevated fasting plasma glucose levels and carotid intima
      media thickness in non-diabetic adults: a population-based cross-sectional study.
AB  - We assessed the association between the mean carotid intima-media thickness
      (CIMT) and fasting plasma glucose (FPG) levels in a low-income population in
      rural China. Adults aged >=45 years without a history of diabetes, stroke, or
      cardiovascular disease were recruited. All participants were categorized into
      four groups according to FPG level. A total of 3509 participants were analyzed in
      this study. In the univariate analysis, sex, age, education level, hypertension,
      central obesity, current smoking, alcohol consumption, and higher levels of FPG,
      total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol
      (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were associated with
      mean CIMT and frequency of increased CIMT. FPG levels were significantly
      associated with mean CIMT; each 1-mmol/L increase in FPG resulted in a 2.75-MUm
      increase in mean CIMT when adjusted by age, sex, education level, current smoking
      status, alcohol consumption, hypertension, and the levels of TC, TG, HDL-C, and
      LDL-C (P = 0.044). However, the association between FPG and the frequency of
      increased CIMT disappeared after adjusting by covariates. These findings indicate
      that FPG is an independent determinant of mean CIMT in a non-diabetic population.
      Management and control of FPG levels is crucial for preventing atherosclerosis in
      populations with high stroke risks in China.

PMID- 29340037
TI  - Systemic bioinformatics analysis of recurrent aphthous stomatitis gene expression
      profiles.
AB  - Recurrent aphthous stomatitis (RAS) represents the most common chronic oral
      diseases with the prevalence ranges from 5% to 25% for different populations. Its
      pathogenesis remains poorly understood, which limits the development of effective
      drugs and treatment methods. In this study, we conducted systemic bioinformatics
      analysis of gene expression profiles from the Gene Expression Omnibus (GEO) to
      identify potential drug targets for RAS. We firstly downloaded the gene
      microarray datasets with the accession number of GSE37265 from GEO and performed
      robust multi-array (RMA) normalization with affy R programming package. Secondly,
      differential expression genes (DEGs) in RAS samples compared with control samples
      were identified based on limma package. Enriched gene ontology (GO) terms and
      Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of DEGs were obtained
      through the Database for Annotation, Visualization and Integrated Discovery
      (DAVID). Finally, protein-protein interaction (PPI) network was constructed based
      on the combination of HPRD and BioGrid databases. What's more, we identified
      modules of PPI network through MCODE plugin of Cytoscape for the purpose of
      screening of valuable targets. As a result, 915 genes were found to be
      significantly differential expression in RAS samples and biological processes
      related to immune and inflammatory response were significantly enriched in those
      genes. Network and module analysis identified FBXO6, ITGA4, VCAM1 and etc as
      valuable therapeutic targets for RAS. Finally, FBXO6, ITGA4, and VCAM1 were
      further confirmed by real time RT-PCR and western blot. This study should be
      helpful for the research and treatment of RAS.

PMID- 29340038
TI  - Diagnostic performance of 68Gallium-PSMA-11 PET/CT to detect significant prostate
      cancer and comparison with 18FEC PET/CT.
AB  - Background: Radiolabeled prostate-specific membrane antigen (PSMA) has proven to
      be a highly accurate method to detect recurrence and metastases of prostate
      cancer, but only sparse data is available about its performance in the diagnosis
      of clinically significant primary prostate cancer. Methods: We compared 68Ga-PSMA
      11 PET/CT in 25 patients with 18FEC PET/CT in 40 patients with suspected prostate
      carcinoma based on an increased PSA level.The PET/CT results were compared with
      the histopathologic Gleason Score (GS) of biopsies. Results: The 68Ga-PSMA-11
      PET/CT revealed highly suspect prostatic lesions (maximum standardized uptake
      value/SUVmax >2.5) in 21/25 patients (84%), associated with GS>=6 (low-grade/high
      grade carcinoma). Two histopathologic non-malignancy-relevant cases (GS<6) had
      PSMA-SUVmax <=2.5; all histopathologic high-grade cases (GS>=7b) showed PSMA
      SUVmax >12.0 which further increased with rising GS. There were 2 false positives
      and no false negative findings for high-grade prostate cancer using a cut off
      level for SUVmax of 2.5.In contrast, the 18FEC PET/CT showed suspected malignant
      lesions in 38/40 patients (95%), which included 3 lesions with GS<6. The mean
      SUVmax values did not differ with different GS. There were 11 false positives and
      1 false negative for detection of high-grade prostate cancer (cut off 2.5).By
      means of ROC analysis a SUVmax of 5.4 was found to be an optimal cut off-level to
      distinguish between low- and high-grade carcinoma in 68Ga-PSMA-11 PET/CT
      (AUC=0.9692; 95% CI 0.9086;1.0000;SD(AUC)=0.0309)). Choosing a cut off-level of
      SUVmax5.4, 68Ga-PSMA-11 PET/CT was able to distinguish between GS <=7a/>=7b with
      a sensitivity of 84%, a specificity of 100%, a negative predictive value (NPV) of
      67%, and an efficiency of 88% (p<0.001).The ROC analysis revealed a SUVmax 6.5 as
      an optimal cut off-level to distinguish between low- and high-grade carcinoma in
      18FEC PET/CT (AUC=0.7470; 95% CI 0.5919;0.9020;SD(AUC)=0.0791) with a sensitivity
      of 61% and a specificity of 92%; but the efficiency was only 70% and the NPV 50%
      (p=0.01). Conclusion: 68Ga-PSMA-11 PET/CT guided biopsy of the prostate increases
      diagnostic precision and is likely to help to reduce overtreatment of low-grade
      malignant disease as well as detect the foci of the highest Gleason pattern. Both
      methods (68Ga-PSMA-11,18FEC) were suitable to detect primary prostate cancer, but
      the excellent image quality, the higher specificity and the good correlation of
      positive scans with GS are advantages of 68Ga-PSMA-11.

PMID- 29340039
TI  - Integrative molecular network analysis identifies emergent enzalutamide
      resistance mechanisms in prostate cancer.
AB  - Recent work demonstrates that castration-resistant prostate cancer (CRPC) tumors
      harbor countless genomic aberrations that control many hallmarks of cancer. While
      some specific mutations in CRPC may be actionable, many others are not. We
      hypothesized that genomic aberrations in cancer may operate in concert to promote
      drug resistance and tumor progression, and that organization of these genomic
      aberrations into therapeutically targetable pathways may improve our ability to
      treat CRPC. To identify the molecular underpinnings of enzalutamide-resistant
      CRPC, we performed transcriptional and copy number profiling studies using paired
      enzalutamide-sensitive and resistant LNCaP prostate cancer cell lines. Gene
      networks associated with enzalutamide resistance were revealed by performing an
      integrative genomic analysis with the PAthway Representation and Analysis by
      Direct Reference on Graphical Models (PARADIGM) tool. Amongst the pathways
      enriched in the enzalutamide-resistant cells were those associated with MEK,
      EGFR, RAS, and NFKB. Functional validation studies of 64 genes identified 10
      candidate genes whose suppression led to greater effects on cell viability in
      enzalutamide-resistant cells as compared to sensitive parental cells. Examination
      of a patient cohort demonstrated that several of our functionally-validated gene
      hits are deregulated in metastatic CRPC tumor samples, suggesting that they may
      be clinically relevant therapeutic targets for patients with enzalutamide
      resistant CRPC. Altogether, our approach demonstrates the potential of
      integrative genomic analyses to clarify determinants of drug resistance and
      rational co-targeting strategies to overcome resistance.

PMID- 29340040
TI  - Identifying the dynamics of actin and tubulin polymerization in iPSCs and in iPSC
      derived neurons.
AB  - The development of the nervous system requires cytoskeleton-mediated processes
      coordinating self-renewal, migration, and differentiation of neurons. It is not
      surprising that many neurodevelopmental problems and neurodegenerative disorders
      are caused by deficiencies in cytoskeleton-related genes. For this reason, we
      focus on the cytoskeletal dynamics in proliferating iPSCs and in iPSC-derived
      neurons to better characterize the underpinnings of cytoskeletal organization
      looking at actin and tubulin repolymerization studies using the cell permeable
      probes SiR-Actin and SiR-Tubulin. During neurogenesis, each neuron extends an
      axon in a complex and changing environment to reach its final target. The dynamic
      behavior of the growth cone and its capacity to respond to multiple spatial
      information allows it to find its correct target. We decided to characterize
      various parameters of the actin filaments and microtubules. Our results suggest
      that a rapid re-organization of the cytoskeleton occurs 45 minutes after
      treatments with de-polymerizing agents in iPSCs and 60 minutes in iPSC-derived
      neurons in both actin filaments and microtubules. The quantitative data confirm
      that the actin filaments have a primary role in the re-organization of the
      cytoskeleton soon after de-polymerization, while microtubules have a major
      function following cytoskeletal stabilization. In conclusion, we investigate the
      possibility that de-polymerization of the actin filaments may have an impact on
      microtubules organization and that de-polymerization of the microtubules may
      affect the stability of the actin filaments. Our results suggest that a
      reciprocal influence of the actin filaments occurs over the microtubules and vice
      versa in both in iPSCs and iPSC-derived neurons.

PMID- 29340041
TI  - Discovery of a highly selective KIT kinase primary V559D mutant inhibitor for
      gastrointestinal stromal tumors (GISTs).
AB  - KIT kinase V559D mutation is the most prevalent primary gain-of-function mutation
      in Gastrointestinal Stromal Tumors (GISTs). Here we reported a highly selective
      KIT V559D inhibitor CHMFL-KIT-031, which displayed about 10-20 fold selectivity
      over KIT wt in the biochemical assay (IC50: 28 nM over 168 nM; Kd: 266 nM versus
      6640 nM) and in cell (EC50: 176 nM versus 2000 nM for pY703) examination. It also
      displayed 15~400-fold selectivity over other primary mutants such as L576P and
      secondary mutants including T670I, V654A (ATP binding pocket) as well as N822K
      and D816V (activation loop). In addition, it exhibited a selectivity S score (1)
      of 0.01 among 468 kinases/mutants in the KINOMEScanTM assay. CHMFL-KIT-031 showed
      potent inhibitory efficacy for KIT V559D mediated signaling pathways in cell and
      anti-tumor activity in vivo (Tumor Growth Inhibition: 68.5%). Its superior
      selectivity would make it a good pharmacological tool for further dissection of
      KIT V559D mediated pathology in the GISTs.

PMID- 29340042
TI  - Identification of potential genetic causal variants for rheumatoid arthritis by
      whole-exome sequencing.
AB  - Rheumatoid arthritis (RA) is a highly prevalent chronic autoimmune disease.
      However, genetic and environmental factors involved in RA pathogenesis are still
      remained largely unknown. To identify the genetic causal variants underlying
      pathogenesis and disease progression of RA patients, we undertook the first
      comprehensive whole-exome sequencing (WES) study in a total of 124 subjects
      including 58 RA cases and 66 healthy controls in Han Chinese population. We
      identified 378 novel genes that were enriched with deleterious variants in RA
      patients using a gene burden test. The further functional effects of associated
      genetic genes were classified and assessed, including 21 newly identified genes
      that were involved in the extracellular matrix (ECM)-receptor interaction,
      protein digestion and absorption, focal adhesion and glycerophospholipid
      metabolism pathways relevant to RA pathogenesis. Moreover, six pathogenic
      variants were investigated and structural analysis predicted their potentially
      functional alteration by homology modeling. Importantly, five novel and rare
      homozygous variants (NCR3LG1, RAP1GAP, CHCHD5, HIPK2 and DIAPH2) were identified,
      which may exhibit more functional impact on RA pathogenesis. Notably, 7 genes
      involved in the olfactory transduction pathway were enriched and associated with
      RA disease progression. Therefore, we performed an efficient and powerful
      technique WES in Chinese RA patients and identified novel, rare and common
      disease causing genes that alter innate immunity pathways and contribute to the
      risk of RA. Findings in this study may provide potential diagnostic tools and
      therapeutic strategies for RA patients.

PMID- 29340043
TI  - Clinical significance of YAP1 activation in head and neck squamous cell
      carcinoma.
AB  - By analyzing the genomic data of head and neck squamous cell cancer (HNSCC), we
      investigated clinical significance of YAP1 activation. Copy number and mRNA
      expression of YAP1 were analyzed together to assess clinical relevance of YAP1
      activation in HNSCC. The clinical significance of YAP1 activation was further
      validated in four independent test cohorts. We also assessed the correlation of
      YAP1 activation with genomic alterations such as copy number alteration, somatic
      mutation, and miRNA expression. The YAP1-activated (YA) subgroup showed worse
      prognosis for HNSCC as tested and validated in five cohorts. In a multivariate
      risk analysis, the YAP1 signature was the most significant predictor of overall
      survival. The YAP1-inactivated (YI) subgroup was associated with HPV-positive
      status. In multiplatform analysis, YA tumors had gain of EGFR and SNAI2; loss of
      tumor-suppressor genes such as CSMD1, CDKN2A, NOTCH1, and SMAD4; and high
      mutation rates of TP53 and CDKN2A. YI tumors were characterized by gain of
      PIK3CA, SOX2, and TP63; deletion of 11q23.1; and high mutation rates of NFE2L2,
      PTEN, SYNE1, and NSD1. YA tumors also showed weaker immune activity as reflected
      in low IFNG composite scores and YAP1 activity is negatively associated with
      potential response to treatment of pembrolizumab. In conclusion, activation of
      YAP1 is associated with worse prognosis of patients with HNSCC and potential
      resistance to immunotherapy.

PMID- 29340045
TI  - RIP140 and LCoR expression in gastrointestinal cancers.
AB  - The transcription coregulators RIP140 and LCoR are part of a same complex which
      controls the activity of various transcription factors and cancer cell
      proliferation. In this study, we have investigated the expression of these two
      genes in human colorectal and gastric cancers by immunohistochemistry. In both
      types of tumors, the levels of RIP140 and LCoR appeared highly correlated. Their
      expression tended to decrease in colorectal cancer as compared to adjacent normal
      tissues but was found higher in gastric cancer as compared to normal stomach.
      RIP140 and LCoR expression correlated with TNM and tumor differentiation.
      Significant correlations were observed with expression levels of key proteins
      involved in tumor progression and invasion namely E-cadherin and Cyclooxygenase
      2. Survival analysis showed that patients with LCoRlow/RIP140high colorectal
      tumors have a significant prolonged overall and disease-free survival. In gastric
      cancer, high LCoR expression was identified as an independent marker of poor
      prognosis suggesting a key role in this malignancy. Altogether, these results
      demonstrate that RIP140 and LCoR have a prognostic relevance in gastrointestinal
      cancers and could represent new potential biomarkers in these tumors.

PMID- 29340044
TI  - Cepharanthine hydrochloride reverses the mdr1 (P-glycoprotein)-mediated
      esophageal squamous cell carcinoma cell cisplatin resistance through JNK and p53
      signals.
AB  - Esophageal squamous cell carcinoma (ESCC) is an aggressive malignancy that is
      often resistant to therapy. Nowadays, chemotherapy is still one of the main
      methods for the treatment of ESCC. However, the multidrug resistance (MDR)
      mediated chemotherapy resistance is one of the leading causes of death. Exploring
      agents able to reverse MDR, which thereby increase the sensitivity with clinical
      first-line chemotherapy drugs, could significantly improve cancer treatment.
      Cepharanthine hydrochloride (CEH) has the ability to reverse the MDR in ESCC and
      the mechanism involved have not been reported. The aim of the study was to
      investigate the potential of CEH to sensitize chemotherapeutic drugs in ESCC and
      explore the underlying mechanisms by in vitro and in vivo studies. Our data
      demonstrated that CEH significantly inhibited ESCC cell proliferation in a dose
      dependent manner, induced G2/M phase cell cycle arrest and apoptosis, and
      increased the sensitivity of cell lines resistant to cisplatin (cDDP).
      Mechanistically, CEH inhibited ESCC cell growth and induced apoptosis through
      activation of c-Jun, thereby inhibiting the expression of P-gp, and enhancing p21
      expression via activation of the p53 signaling pathway. In this study, we
      observed that growth of xenograft tumors derived from ESCC cell lines in nude
      mice was also significantly inhibited by combination therapy. To our knowledge,
      we demonstrate for the first time that CEH is a potentially effective MDR
      reversal agent for ESCC, based on downregulation of the mRNA expression of MDR1
      and P-gp. Together, these results reveal emphasize CEH putative role as a
      resistance reversal agent for ESCC.

PMID- 29340046
TI  - Sampling from single-cell observations to predict tumor cell growth in-vitro and
      in-vivo.
AB  - Cancer stem-like cells (CSCs) are a topic of increasing importance in cancer
      research, but are difficult to study due to their rarity and ability to rapidly
      divide to produce non-self-cells. We developed a simple model to describe
      transitions between aldehyde dehydrogenase (ALDH) positive CSCs and ALDH(-) bulk
      ovarian cancer cells. Microfluidics device-isolated single cell experiments
      demonstrated that ALDH+ cells were more proliferative than ALDH(-) cells. Based
      on our model we used ALDH+ and ALDH(-) cell division and proliferation properties
      to develop an empiric sampling algorithm and predict growth rate and CSC
      proportion for both ovarian cancer cell line and primary ovarian cancer cells, in
      vitro and in-vivo. In both cell line and primary ovarian cancer cells, the
      algorithm predictions demonstrated a high correlation with observed ovarian
      cancer cell proliferation and CSC proportion. High correlation was maintained
      even in the presence of the EGF-like domain multiple 6 (EGFL6), a growth factor
      which changes ALDH+ cell asymmetric division rates and thereby tumor growth
      rates. Thus, based on sampling from the heterogeneity of in-vitro cell growth and
      division characteristics of a few hundred single cells, the simple algorithm
      described here provides rapid and inexpensive means to generate predictions that
      correlate with in-vivo tumor growth.

PMID- 29340047
TI  - Inhibition of polo-like kinase 4 (PLK4): a new therapeutic option for rhabdoid
      tumors and pediatric medulloblastoma.
AB  - Rhabdoid tumors (RT) are highly aggressive and vastly unresponsive embryonal
      tumors. They are the most common malignant CNS tumors in infants below 6 months
      of age. Medulloblastomas (MB) are embryonal tumors that arise in the cerebellum
      and are the most frequent pediatric malignant brain tumors. Despite the advances
      in recent years, especially for the most favorable molecular subtypes of MB, the
      prognosis of patients with embryonal tumors remains modest with treatment related
      toxicity dreadfully high. Therefore, new targeted therapies are needed. The polo
      like kinase 4 (PLK4) is a critical regulator of centriole duplication and
      consequently, mitotic progression. We previously established that PLK4 is
      overexpressed in RT and MB. We also demonstrated that inhibiting PLK4 with a
      small molecule inhibitor resulted in impairment of proliferation, survival,
      migration and invasion of RT cells. Here, we showed in MB the same effects that
      we previously described for RT. We also demonstrated that PLK4 inhibition induced
      apoptosis, senescence and polyploidy in RT and MB cells, thereby increasing the
      susceptibility of cancer cells to DNA-damaging agents. In order to test the
      hypothesis that PLK4 is a CNS druggable target, we demonstrated efficacy with
      oral administration to an orthotropic xenograft model. Based on these results, we
      postulate that targeting PLK4 with small-molecule inhibitors could be a novel
      strategy for the treatment of RT and MB and that PLK4 inhibitors (PLK4i) might be
      promising agents to be used solo or in combination with cytotoxic agents.

PMID- 29340048
TI  - Alteration of mitochondrial biogenesis promotes disease progression in multiple
      myeloma.
AB  - Many cancers, including multiple myeloma (MM), retain more cytosolic iron to
      promote tumor cell growth and drug resistance. Higher cytosolic iron promotes
      oxidative damage due to its interaction with reactive oxygen species generated by
      mitochondria. The variation of mitochondrial biogenesis in different stages of MM
      disease was evaluated using gene expression profiles in a large clinical dataset.
      Sixteen of 18mitochondrial biogenesis related gene sets, including mitochondrial
      biogenesis signature and oxidative phosphorylation, were increased in myeloma
      cells compared with normal plasma cells and high expression was associated with
      an inferior patient outcome. Relapsed and drug resistant myeloma samples had
      higher expression of mitochondrial biogenesis signatures than newly diagnosed
      patient samples. The expression of mitochondrial biogenesis genes was regulated
      by the cellular iron content, which showed a synergistic effect in patient
      outcome in MM. Pharmacological ascorbic acid induced myeloma cell death by
      inhibition of mitochondria oxidative phosphorylation in an in vivo model. Here,
      we identify that dysregulated mitochondrial biogenesis and iron homeostasis play
      a major role in myeloma progression and patient outcome and that pharmacological
      ascorbic acid, through cellular iron content and mitochondrial oxidative species,
      should be considered as a novel treatment in myeloma including drug-resistant and
      relapsed patients.

PMID- 29340050
TI  - Molecular characteristics and clinical outcomes of EGFR exon 19 indel subtypes to
      EGFR TKIs in NSCLC patients.
AB  - Patients with non-small cell lung cancer (NSCLC) with activating epidermal growth
      factor receptor (EGFR) mutations (exon 19 deletions and L858R) benefit from EGFR
      tyrosine kinase inhibitors (TKIs). However, some researchers have reported that
      responses to TKIs differ by subtypes of EGFR exon 19 mutations. We
      retrospectively analyzed EGFR exon 19 deletion subtypes and their correlation
      with clinical outcomes of treatment with TKIs. A cohort of 2664 consecutive
      patients with NSCLC was enrolled. A total of 440 EGFR exon 19 deletions were
      defined as 39 subtypes. Among them, 158 patients with advanced lung
      adenocarcinoma with EGFR exon 19 deletion mutations received EGFR-TKIs. There
      were no significant differences in progression-free survival or overall survival
      among patients with non-LRE deletions, delE746, or delL747 (P = 0.463 and P =
      0.464, respectively). Furthermore, two patients with EGFR exon19 insertion had
      durable response to EGFR-TKIs. In conclusion, EGFR exon 19 is highly fragile,
      resulting in many different deletion and insertion subtypes. There were no
      significant differences in clinical outcomes after TKI treatment across the
      different subtypes. It is necessary to attempt to identify all patients with exon
      19 deletions so that they can be offered TKI treatment.

PMID- 29340049
TI  - Pharmacological treatment with inhibitors of nuclear export enhances the
      antitumor activity of docetaxel in human prostate cancer.
AB  - Background and aims: Docetaxel (DTX) modestly increases patient survival of
      metastatic castration-resistant prostate cancer (mCRPC) due to insurgence of
      pharmacological resistance. Deregulation of Chromosome Region Maintenance (CRM
      1)/ exportin-1 (XPO-1)-mediated nuclear export may play a crucial role in this
      phenomenon. Material and methods: Here, we evaluated the effects of two Selective
      Inhibitor of Nuclear Export (SINE) compounds, selinexor (KPT-330) and KPT-251, in
      association with DTX by using 22rv1, PC3 and DU145 cell lines with their. DTX
      resistant derivatives. Results and conclusions: We show that DTX resistance may
      involve overexpression of beta-III tubulin (TUBB3) and P-glycoprotein as well as
      increased cytoplasmic accumulation of Foxo3a. Increased levels of XPO-1 were also
      observed in DTX resistant cells suggesting that SINE compounds may modulate DTX
      effectiveness in sensitive cells as well as restore the sensitivity to DTX in
      resistant ones. Pretreatment with SINE compounds, indeed, sensitized to DTX
      through increased tumor shrinkage and apoptosis by preventing DTX-induced cell
      cycle arrest. Basally SINE compounds induce FOXO3a activation and nuclear
      accumulation increasing the expression of FOXO-responsive genes including p21,
      p27 and Bim causing cell cycle arrest. SINE compounds-catenin and survivin
      supporting apoptosis. betadown-regulated Cyclin D1, c-myc, Nuclear sequestration
      of p-Foxo3a was able to reduce ABCB1 and TUBB3 H2AX levels, prolonged gamma
      expression. Selinexor treatment increased DTX-mediated double strand breaks
      (DSB), and reduced the levels of DNA repairing proteins including DNA PKc and
      Topo2A. Our results provide supportive evidence for the therapeutic use of SINE
      compounds in combination with DTX suggesting their clinical use in mCRPC
      patients.

PMID- 29340051
TI  - MicroRNA-34a inhibits cells proliferation and invasion by downregulating Notch1
      in endometrial cancer.
AB  - MicroRNAs (miRNAs) are small non-coding RNAs composed of 18-25 nucleotides that
      regulate the expression of approximately 30% of human protein coding genes.
      Dysregulation of miRNAs plays a pivotal role in the initiation and progression of
      malignancies. Our study has shown that microRNA-34a (miR-34a) was upregulated in
      human endometrial cancer stem cells (ECSCs). However, it is unknown how miR-34a
      regulates endometrial cancer itself. Here, we report that miR-34a directly and
      functionally targeted Notch1. MiR-34a inhibited the proliferation, migration,
      invasion, EMT-associated phenotypes by downregulating Notch1 in endometrial
      cancer cells. Overexpression of miR-34a also suppressed tumor growth in nude
      mice. Importantly, further results suggested miR-34a was significantly
      downregulated in endometrial cancer tissues and negatively correlated with Notch1
      expression. There was a significant association between decreased miR-34a
      expression and worse patient prognosis. Taken together, our results suggest that
      miR-34a plays tumor-suppressive roles in endometrial cancer through
      downregulating Notch1. Thus miR-34a could be a potential therapeutic target for
      prevention and treatment of endometrial cancer.

PMID- 29340052
TI  - Gene expression profiling and construction of a putative gene regulatory network
      of bladder cancer tumor-initiating cells.
AB  - Human bladder cancer tumors have been shown to contain a subpopulation of cells
      with stem-like characteristics that may trigger tumor growth, recurrence, and
      metastasis. These cells, known as tumor-initiating cells (TICs), would be
      effective diagnostic tools and valuable therapeutic targets. Here, we report the
      isolation of TICs from seven bladder cancer cell lines and show that TICs from
      different sources vary on their ability to form tumorspheres in vitro and
      generate xenografts in vivo, which suggest they are remarkably heterogeneous. We
      used the Affymetrix PrimeViewTM Human Gene Expression Array to analyze gene
      expression profiles of bladder TICs, which may help understand their tumorigenic
      capacities and develop novel treatments specifically targeted toward these cells.
      We then constructed a transcription factor-gene regulatory network that includes
      three key transcription factors that are involved in cell survival,
      differentiation, proliferation, and apoptosis. We validated our findings by
      analyzing mRNA expression of the key genes in this network in 24 clinical
      tissues. Our results suggest that this transcription factor-gene regulatory
      network could be useful in the development of clinical diagnostic tools and
      therapy approaches for bladder cancer.

PMID- 29340053
TI  - Indomethacin-based stimuli-responsive micelles combined with paclitaxel to
      overcome multidrug resistance.
AB  - Development of multidrug resistance against antitumor agents is a major limiting
      factor for the successful chemotherapy. Currently, both amphiphilic polymeric
      micelles and chemosensitizers have been proposed to overcome MDR during
      chemotherapy. Herein, the redox-responsive polymeric micelles composed of dextran
      and indomethacin (as chemosensitizer) using a disulfide bond as the linker are
      prepared (DEX-SS-IND) for delivery of antitumor agent paclitaxel (PTX). The high
      level of glutathione in tumor cells selectively breaks the disulfide bond,
      leading to the rapid breakdown and deformation of redox-responsive polymeric
      micelles. The data show that DEX-SS-IND can spontaneously form the stable
      micelles with high loading content (9.48 +/- 0.41%), a favorable size of 45 nm
      with a narrow polydispersity (0.157), good stability, and glutathione-triggered
      drug release behavior due to the rapid breakdown of disulfide bond between DEX
      and IND. In vitro antitumor assay shows DEX-SS-IND/PTX micelles effectively
      inhibit the proliferation of PTX-resistant breast cancer (MCF-7/PTX) cells. More
      impressively, DEX-SS-IND/PTX micelles possess the improved plasma
      pharmacokinetics, enhanced antitumor efficacy on tumor growth in the xenograft
      models of MCF-7/PTX cells, and better in vivo safety. Overall, DEX-SS-IND/PTX
      micelles display a great potential for cancer treatment, especially for multidrug
      resistance tumors.

PMID- 29340054
TI  - Febuxostat attenuates ER stress mediated kidney injury in a rat model of
      hyperuricemic nephropathy.
AB  - Hyperuricemia contributes to kidney tubular injury and kidney fibrosis. However,
      the underlying mechanism remains unclear. Here we examined the role of RTN1A, a
      novel endoplasmic reticulum (ER)-associated protein and ER stress in
      hyperuricemic nephropathy. We first found the expression of RTN1A and ER stress
      markers was significantly increased in kidney biopsies of hyperuricemia patients
      with kidney injury. In a rat model of hyperuricemic nephropathy (HN) established
      by oral administration of a mixture of adenine and potassium oxonate, increased
      expression of RTN1A and ER stress was shown in tubular and interstitial
      compartment of rat kidneys. Treatment of Febuxostat, a new selective inhibitor of
      xanthine oxidase (XO), not only attenuated renal tubular injury and
      tubulointerstitial fibrosis, but also reduced uric acid crystals deposition in HN
      rat kidneys. In vitro, Febuxostat also reduced ER stress and apoptosis in uric
      acid treated tubular epithelial cells. Our data suggest that RTN1A and ER stress
      mediate tubular cell injury and kidney fibrosis in HN. Urate-lowering therapy
      (ULT) with Febuxostat attenuates uric-acid induced ER stress in renal tubular
      cells and the progression of HN.

PMID- 29340055
TI  - Concurrent brain radiotherapy and EGFR-TKI may improve intracranial metastases
      control in non-small cell lung cancer and have survival benefit in patients with
      low DS-GPA score.
AB  - Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) has
      intracranial activity in EGFR-mutant Non-Small Cell Lung Cancer (NSCLC). The
      optimal timing of brain radiotherapy (RT) and appropriate patients who need early
      brain RT remains undetermined. This is a retrospective study of EGFR-mutant NSCLC
      patients with newly diagnosed brain metastases (BMs) before EGFR-TKI initiation.
      Intra-cranial progression free survival (IC-PFS) and overall survival (OS) were
      measured from the date of EGFR-TKI treatment. A total of 113 patients were
      eligible, 49 received concurrent early brain RT with EGFR-TKI and 64 were treated
      with EGFR-TKI alone as initial therapy, including 27 with salvage RT upon BM
      progression. The patients with early brain RT had superior IC-PFS than those
      without early brain RT (21.4 vs 15.0 months, P=0.001), which remained significant
      in multivariate analysis (HR 0.30, P<0.001). The median overall survival (OS) for
      early RT, EGFR-TKI alone and salvage RT groups was 28.1, 24.5, and 24.6 months,
      respectively (P=0.604). Similar IC-PFS (23.6 vs 21.4 months, P=0.253) and OS
      (24.6 vs 28.1 months, P=0.385) were observed between salvage RT and early RT
      groups. For patients with Diagnosis-Specific Graded Prognostic Assessment (DS
      GPA) score of 0 to 2, early brain RT was the independent factor for improved OS
      (HR 0.33, P=0.025). In conclusion, concurrent early brain RT with EGFR-TKI may
      improve intracranial disease control in EGFR-mutant NSCLC with BM and have
      survival benefit in patients with low DS-GPA score. Salvage brain RT upon BM
      progression may be acceptable in some patients.

PMID- 29340056
TI  - Temozolomide encapsulated and folic acid decorated chitosan nanoparticles for
      lung tumor targeting: improving therapeutic efficacy both in vitro and in vivo.
AB  - Folic acid-conjugated temozolomide (TMZ)-loaded chitosan nanoparticles (CS-TMZ
      FLA-NP) were developed to target lung cancer in the anticipation that folic acid
      would increase the affinity of nanoparticles for cancer cells. CS-TMZ-FLA-NP
      showed the highest anti-proliferative effect on the lung cancer cells in
      comparison to free TMZ and CS-TMZ-NP (nanoparticles without folic acid). A
      cellular uptake assay was performed on two different cell lines, L132 and A549.
      Cellular uptake efficiencies of CS-TMZ-NP and CS-TMZ-FLA-NP were found to be
      concentration-dependent in both cell lines. CS-TMZ-FLA-NP produced a 2.5 fold
      greater accumulation of TMZ than CS-TMZ-NP in both cell lines. CS-TMZ-FLA-NP
      maintained a significantly higher deposition of TMZ in lung tissue (approximately
      7.5 MUg/g of lung tissue) when compared to free TMZ and CS-TMZ-NP. Mice treated
      with CS-TMZ-FLA-NP had a 100% survival rate with significant suppression of tumor
      growth. Histopathological and immunohistochemical studies also demonstrated that
      CS-TMZ-FLA-NP had superior anticancer activity compared to the other two
      treatments. Our results indicate that CS-TMZ-FLA-NP can effectively facilitate
      targeting to human lung cancer cell lines in vitro and to lung tumors in vivo in
      a sustained manner and so improve the therapeutic efficacy of TMZ.

PMID- 29340057
TI  - Aberrant expression of STYK1 and E-cadherin confer a poor prognosis for
      pancreatic cancer patients.
AB  - Previous studies showed that aberrant Serine/threonine/tyrosine kinase 1 (STYK1,
      also known as NOK) or/and E-cadherin were involved in the progression of some
      types of human cancers. However, whether they contributed to the development of
      pancreatic cancer was unknown. Here, we investigated the prognostic significance
      of aberrant STYK1 and E-cadherin in pancreatic cancer. Our results showed that
      STYK1 expression increased while E-cadherin decreased in pancreatic cancer
      tissues compared with normal pancreas tissues. STYK1 level was positively
      correlated with lymph node metastasis and clinical stage in pancreatic cancer
      patients. E-cadherin expression was inversely correlated with STYK1 expression in
      pancreatic cancer tissue samples. Patients with high STYK1 and low E-cadherin
      expression had the worst prognosis. In addition, STYK1 knockdown in pancreatic
      cancer cell lines inhibited cell proliferation, enhanced cell apoptosis, induced
      cell cycle arrest, and prohibited cell migration, while STYK1 over-expression
      showed the opposite effects. Silencing STYK1 also increased E-cadherin expression
      and inhibited epithelial-to-mesenchymal transition (EMT) and p-p38 expression in
      vitro. Over-expression had showed the opposite trends, and treatment with p38
      inhibitor, SB203580, could reverse the trends. Thus, STYK1 repressed E-cadherin
      expression and promoted EMT, mediated by p38 MAPK signaling pathway, which was
      the possible mechanism for STYK1-mediated pancreatic cancer cell proliferation
      and migration. In summary, our results showed that STYK1 might be a prognostic
      marker for pancreatic cancer patients and might be a novel strategy for the
      treatment of pancreatic cancer.

PMID- 29340058
TI  - A multicenter prospective phase II study of first-line modified FOLFIRINOX for
      unresectable advanced pancreatic cancer.
AB  - Background: FOLFIRINOX (FX) has been reported as an effective treatment for
      unresectable advanced pancreatic cancer. However, FX is associated with a high
      incidence of adverse events (AEs). A previous phase II study in Japan showed high
      incidences of hematological AEs, including febrile neutropenia (22.2%). A
      modified FX regimen (mFX) may decrease the rates of AEs and be more effective
      than FX by improving the treatment compliance. Aims: To assess the safety and
      efficacy of first-line mFX for unresectable advanced pancreatic cancer. Patients
      and methods: This was as a multicenter prospective phase II study in chemotherapy
      naive Japanese patients with pathologically confirmed unresectable advanced
      pancreatic adenocarcinoma or adenosquamous carcinoma. Treatment with mFX (85
      mg/m2 oxaliplatin, 150 mg/m2 irinotecan, and 200 mg/m2 l-leucovorin, followed by
      46-h continuous infusion of 2400 mg/m2 5-fluorouracil) was administered every 2
      weeks. The primary endpoint was the response rate. The secondary endpoints were
      overall survival, progression-free survival, and safety. Results: Thirty-one
      patients (18 men; median age, 64 years) were enrolled. A median of 13 treatment
      cycles were administered during a median follow-up period of 14.2 months. The
      response rate, median overall survival, and median progression-free survival were
      38.7%, 14.9 months, and 7.0 months, respectively. Grade 3 or 4 AEs included
      neutropenia (83.9%), febrile neutropenia (16.1%), peripheral sensory neuropathy
      (9.7%), thrombocytopenia (6.5%), diarrhea (6.5%), anorexia (6.5%), and vomiting
      (3.2%). Conclusion: Compared to FX, mFX may result in fewer Grade 3 or 4 non
      hematological AEs, with a comparable response rate. However, further efforts
      might be required to reduce hematological AEs.

PMID- 29340059
TI  - MicroRNA-95 promotes myogenic differentiation by down-regulation of aminoacyl
      tRNA synthase complex-interacting multifunctional protein 2.
AB  - MicroRNA-95 (miR-95) is well known for its ability to promote the proliferation
      of a variety of cancer cells, but its function in skeletal muscle development has
      not been reported so far. Our laboratory has recently generated genetically
      engineered Meishan pigs containing a loss-of-function myostatin (MSTN) mutant
      (MSTN-/-). These MSTN-/- pigs grow and develop normally but show clear double
      muscle phenotype as observed in Belgian cattle. We observed that the expression
      of miR-95 was up-regulated in the longissimus dorsi from MSTN-/- Meishan pigs at
      day 65 during embryo development. In this study, we investigated the role of miR
      95 in the myogenic differentiation using a murine myoblast cell line C2C12. Our
      results revealed that miR-95 may play a very important role in regulating the
      expression of myogenic differentiation marker genes myosin heavy chain (MHC) and
      myogenin. By use of bioinformatical analysis and luciferase reporter gene assay,
      aminoacyl-tRNA synthase complex-interacting multifunctional protein 2 (AIMP2)
      gene was identified as a miR-95 target gene involved in myogenic differentiation.
      Our results indicated that higher miR-95 expression level leads to lower level of
      AIMP2 protein expression. When the endogenous expression of AIMP2 is inhibited by
      siRNA, the expression levels of myogenic differentiation marker genes MHC and
      myogenin increased, implying that AIMP2 negatively regulates myogenic
      differentiation. Taken together, it is likely that miR-95 promotes myogenic
      differentiation in C2C12 myoblasts and may play a positive functional role in
      skeletal muscle development by down regulating the expression of AIMP2 at protein
      level.

PMID- 29340060
TI  - Assessment of antimicrobial and wound healing effects of Brevinin-2Ta against the
      bacterium Klebsiella pneumoniae in dermally-wounded rats.
AB  - Antimicrobial peptides (AMPs) are regarded as promising alternatives for
      antibiotics due to their inherent capacity to prevent microbial drug resistance.
      Amphibians are rich source of bioactive molecules, which provide numerous AMPs
      with various structures as drug candidates. Here, we isolated and identified a
      novel AMP Brevinin-2Ta (B-2Ta) from the skin secretion of the European frog,
      Pelophylax kl. esculentus. In vitro studies revealed that it showed broad
      antimicrobial activities against S. aureus, E. coli and C. albicans with low
      cytotoxicity to erythrocytes. Furthermore, we examined the anti-inflammation
      effect in vivo by using Klebsiella pneumoniae-infected Sprague-Dawley (SD) rats.
      The wound closure outcomes revealed that B-2Ta effectively restrained the
      bacterial infection at a dose of 10 times minimal inhibitory concentration (MIC)
      during the 14 days of the wound healing process. Ultra-structure analyses showed
      that B-2Ta caused structural damage to the microorganism, and bacterial culture
      found that the number of microbes was significantly reduced by the end of
      treatment. Immunohistochemistry for the inflammatory marker IL-10 and the
      endothelial cell marker CD31 suggested positive effects on inflammatory status
      and epithelial migration and angiogenesis following treatment of the infected
      granulation tissues with B-2Ta. These results exhibited the continuous phase of
      inflammation reduction and wound healing acceleration in the B-2Ta-modulated re
      epithelialisation of K. pneumoniae infected rats. Taken together, these data
      demonstrated that B-2Ta has great potential to be developed as antibacterial
      agents in clinic.

PMID- 29340062
TI  - Correlation of psychooncological distress- screening and quality of life
      assessment in neurosurgical patients.
AB  - Background: Cerebral tumors are associated with high rates of anxiety, depression
      and reduced health related quality of life. But still psychooncological screening
      instruments are not implemented in the daily routine of neurosurgical
      departments. In contrast the EORTC QLQ-C30/ EORTC QLQ- BN20 questionnaire is
      often used to evaluate quality of life in the framework of clinical studies. We
      were therefore interested, if conspicuous distress screening results are also
      reflected by HRQOL assessment. Patients and Methods: Patients who were electively
      admitted for surgery of intracranial lesions were screened for their
      psychooncological distress using two self-assessment instruments (Hospital
      Anxiety and Depression Scale (HADS) and Distress Thermometer (DT)) and one
      external assessment questionnaire (Psychooncological base documentation (PO
      Bado). Results were correlated with three subscales of the EORTC-QLQ-C30 and
      EORTC-QLQ-BN20 questionnaire. Results: From October 2013 to March 2015, 594
      patients were admitted for elective cranial neurosurgical procedure. 489
      neurosurgical patients were screened for increased distress. Data from 450
      patients could be correlated with the EORTC-QLQ-C30 and EORTC-QLQ-BN20. In 265
      patients screening revealed increased distress. A concurrent reduced global
      health /higher rates of future uncertainty and conspicuous distress screening
      results are found in 173 patients (69.5%) compared to 30.5% of patients (n= 76)
      with unremarkable screening. Increased distress screening was highly significant
      with increased level of future uncertainty as well as decreased level of quality
      of life and global health (p<0.0001). Conclusion: Psychooncological distress is
      accompanied by reduced quality of life, global heath and increased future
      uncertainty. Therefore HQOL assessment can be helpful identifying patients with
      increased distress.

PMID- 29340061
TI  - Analysis of the mutational landscape of classic Hodgkin lymphoma identifies
      disease heterogeneity and potential therapeutic targets.
AB  - Defining the mutational landscape of classic Hodgkin lymphoma is still a major
      research goal. New targeted next-generation sequencing (NGS) techniques may
      identify pathogenic mechanisms and new therapeutic opportunities related to this
      disease. We describe the mutational profile of a series of 57 cHL cases, enriched
      in Hodgkin and Reed-Sternberg (HRS) cells. Overall, the results confirm the
      presence of strong genomic heterogeneity. However, several variants were
      consistently detected in genes related to relevant signaling pathways, such as GM
      CSF/IL-3, CBP/EP300, JAK/STAT, NF-kappaB, and numerous variants of genes
      affecting the B-cell receptor (BCR) pathway, such as BTK, CARD11, BCL10, among
      others. This unexpectedly high prevalence of mutations affecting the BCR pathway
      suggests some requirement for active BCR signaling for cHL cell viability.
      Additionally, incubation of a panel of cHL cellular models with selective BTK
      inhibitors in vitro constrains cell proliferation and causes cell death. Our
      results indicate new pathogenic mechanisms and therapeutic opportunities in this
      disease.

PMID- 29340064
TI  - Antitumor activity of resveratrol against human osteosarcoma cells: a key role of
      Cx43 and Wnt/beta-catenin signaling pathway.
AB  - Osteosarcoma is a high-grade bone sarcoma with strong invasive ability. However,
      treatment with traditional chemotherapeutic drugs is limited by low tolerability
      and side effects. Resveratrol has been reported previously to have selective
      antitumor effect on various tumor cells while little is known about its effects
      and underlying mechanism in osteosarcoma biology. In this study, we found that
      resveratrol inhibits proliferation and glycolysis, induces apoptosis and reduces
      the invasiveness of U2-OS cells in vitro. After treatment with resveratrol, the
      expression of related Wnt/beta-catenin signaling pathway target genes, such as
      beta-catenin, c-myc, cyclin D1, MMP-2 and MMP-9, was downregulated and an
      increased E-cadherin level was observed as well. Additionally, the dual
      luciferase assay results also indicated that resveratrol suppressed the activity
      of Wnt/beta-catenin signaling pathway. Interestingly, we noticed that the
      expression of connexin 43 (Cx43) increased with the prolongation of resveratrol
      treatment time. To further investigate the relationship between Cx43 and the
      Wnt/beta-catenin signaling pathway in osteosarcoma, we used lentiviral-mediated
      shRNA to knockdown the expression of Cx43. Knockdown of Cx43 activated the
      Wnt/beta-catenin signaling pathway, promoted proliferation and invasion, and
      inhibited apoptosis of U2-OS cells. Taken together, our results demonstrate that
      the antitumor activity of resveratrol against U2-OS cells in vitro occurs through
      up-regulating Cx43 and E-cadherin, and suppressing the Wnt/beta-catenin signaling
      pathway. Moreover, Cx43 expression is negatively related to the activity of the
      Wnt/beta-catenin pathway in U2-OS cells.

PMID- 29340063
TI  - A molecular signature of dormancy in CD34+CD38- acute myeloid leukaemia cells.
AB  - Dormant leukaemia initiating cells in the bone marrow niche are a crucial
      therapeutic target for total eradication of acute myeloid leukaemia. To study
      this cellular subset we created and validated an in vitro model employing the
      cell line TF-1a, treated with Transforming Growth Factor beta1 (TGFbeta1) and a
      mammalian target of rapamycin inhibitor. The treated cells showed decreases in
      total RNA, Ki-67 and CD71, increased aldehyde dehydrogenase activity, forkhead
      box 03A (FOX03A) nuclear translocation and growth inhibition, with no evidence of
      apoptosis or differentiation. Using human genome gene expression profiling we
      identified a signature enriched for genes involved in adhesion,
      stemness/inhibition of differentiation and tumour suppression as well as
      canonical cell cycle regulation. The most upregulated gene was the osteopontin
      coding gene SPP1. Dormant cells also demonstrated significantly upregulated beta
      3 integrin (ITGB3) and CD44, as well as increased adhesion to their ligands
      vitronectin and hyaluronic acid as well as to bone marrow stromal cells.
      Immunocytochemistry of bone marrow biopsies of AML patients confirmed the
      positive expression of osteopontin in blasts near the para-trabecular bone
      marrow, whereas osteopontin was rarely detected in mononuclear cell isolates.
      Unsupervised hierarchical clustering of the dormancy gene signature in primary
      acute myeloid leukaemia samples from the Cancer Genome Atlas identified a cluster
      enriched for dormancy genes associated with poor overall survival.

PMID- 29340065
TI  - Integrating gene and lncRNA expression to infer subpathway activity for tumor
      analyses.
AB  - LncRNAs acting as miRNA sponges to indirectly regulate mRNAs is a novel layer of
      gene regulation, therefore, it is necessary to integrate lncRNA and gene levels
      for interpreting tumor biological mechanism. In this study, we developed a lncRNA
      gene integrated strategy to infer functional activities for tumor analyses at the
      subpathway level. In this strategy, we reconstructed subpathway graphs by
      embedding lncRNA components and considered the expression levels of both genes
      and lncRNAs to infer subpathway activities for each tumor sample. And the
      activities were applied to three aspects of tumor analyses; First, the subpathway
      activities across tumor samples of five tumor types were analyzed, and it was
      observed that the samples with consistent subpathway activities were derived from
      the same or similar tumor types. Also, the subpathway activities could stratify
      samples into several subtypes which has different clinical characterization, e.g.
      survival status. Second, the subpathway activities between tumor and normal
      samples were analyzed, and the comparative results showed that subpathway
      activities displayed more specificities than entire pathway activities. Finally,
      based on the subpathway activities, we identified prognostic subpathways for lung
      cancer. Our subpathway-based signatures shared significant overlap with
      enrichment analysis results and displayed predictive power in the independent
      testing sets. In conclusion, our integrated strategy provided a framework to
      infer subpathway activities for tumor analyses and identify subpathway signatures
      for clinical use.

PMID- 29340066
TI  - Clinicopathological and prognostic significance of SDC1 overexpression in breast
      cancer.
AB  - Background: Breast cancer is the leading cause of cancer death among global
      women, and its early diagnosis and treatment are very urgent. Syndecan-1 (SDC1)
      is a heparin sulfate proteoglycan, which has been linked with the prognosis and
      treatment response in a various tumor type. To investigate whether SDC1 can serve
      as a prognostic indictor in breast cancer, bioinformatic analyses were performed
      in the present study. Methods: SDC1 expression was assessed using Oncomine
      analysis. Kaplan-Meier Plotter and bc-GenExMiner were performed to identify the
      prognostic roles of SDC1 in breast cancer. COSMIC analysis and cBioPortal
      database were performed to analysis the mutations of SDC1. The heat map and
      methylation status of SDC1 were identified by performing the UCSC. Results: We
      found that SDC1 was more frequently overexpressed in breast cancer than their
      normal tissues and its expression might be negatively related with some CpG
      sites. Meanwhile, pooled data suggested that SDC1 mRNA expression is associated
      worse prognosis of breast cancer. Following data mining in multiple big databases
      confirmed a positive correlation between SDC1 mRNA expression and PLAU mRNA
      expression in breast cancer tissues. In addition, high SDC1 expression is
      associated with increased risked of age, nodal, HER2 and higher SBR grade status.
      Conclusion: Our findings suggest that overexpressed SDC1 was identified in breast
      cancer than in matched normal tissues and is associated with methylation status
      of SDC1 promoter. Additionally, SDC1 is positively associated with PLAU and might
      act as a potential prognostic indicator for breast cancer.

PMID- 29340067
TI  - The effects of tumor necrosis factor-alpha (TNF-alpha) rs1800629 and rs361525
      polymorphisms on sepsis risk.
AB  - This meta-analysis of 23 eligible articles comprehensively and quantitatively
      evaluated the effects of tumor necrosis factor-alpha (TNF-alpha) rs1800629 and
      rs361525 polymorphisms on sepsis risk. We found that TNF-alpha rs1800629 was
      associated with increased sepsis risk in the overall population in four genetic
      models, including A vs. G (P<0.001, odds ratio (OR)=1.32), GA vs. GG (P<0.001,
      OR=1.46), GA+AA vs. GG (P<0.001, OR=1.46), and carrier A vs. carrier G (P<0.001,
      OR=1.32). Subgroup analyses showed a similar result for Asian patients (all
      P<0.05, OR>1). TNF-alpha rs361525 was also associated with increased sepsis risk
      in Asian patients in the four genetic models (all P<0.05, OR>1). Begg's and
      Egger's tests excluded large publication bias, and sensitivity analysis indicated
      stable results. Our results suggest that the G/A genotype of TNF-alpha rs1800629
      and rs361525 increases sepsis risk in an Asian population.

PMID- 29340068
TI  - Chaperonin containing TCP-1 subunit 3 is critical for gastric cancer growth.
AB  - Background: Members of eukaryotic chaperonin family are essential for cell
      survival. Dysregulation of Chaperonin containing TCP-1 subunit 3 (CCT3) has been
      implicated in the development of several types of cancers. However, the role of
      CCT3 in the development of gastric cancer has yet to be determined. Methods: The
      expression patterns of CCT3 in the surgical specimens from 26 gastric cancer
      patients were evaluated using immunohistochemistry methods. To study the possible
      roles of CCT3 in the growth and survival of gastric cancer cells, RNA
      interference was used to knockdown CCT3 expression in gastric cancer cell lines
      BGC-823 and MGC-803. The effects of CCT3 knockdown on cancer cell proliferation,
      apoptosis and in vivo growth were examined. Finally, gene expression changes
      related to CCT3 knockdown were studied using gene array analysis and western
      blotting. Results: Higher level of CCT3 expression was detected in the gastric
      cancer tissue compared to adjacent non-cancerous epithelium. Knockdown of CCT3
      inhibited proliferation and colony formation while promoted apoptosis of gastric
      cancer cells in vitro. Gastric cancer cells exhibited lower growth potential in
      nude mice when CCT3 expression was suppressed. Gene expression analysis showed
      that CCT3 knockdown was associated with down-regulation of mitogen-activated
      protein kinase kinase kinase 7, cell division cycle 42, cyclin D3 and up
      regulation of cyclin-dependent kinase 2 and 6. Conclusion: Our results suggested
      that CCT3 played a critical role in gastric cancer growth and survival. Further
      studies on the mechanisms of CCT3 function is mandated to develop novel cancer
      treatment targeting CCT3.

PMID- 29340069
TI  - Methylenetetrahydrofolate reductase tagging polymorphisms are associated with
      risk of esophagogastric junction adenocarcinoma: a case-control study involving
      2,740 Chinese Han subjects.
AB  - In this study, we aimed to determine the potential association of MTHFR tagging
      single nucleotide polymorphisms (SNPs) with risk of developing esophagogastric
      junction adenocarcinoma (EGJA). MTHFR rs1801133 G>A, rs3753584 T>C, rs4845882
      G>A, rs4846048 A>G and rs9651118 T>C polymorphisms were genotyped in 1,677
      healthy individuals and 1,063 patients with EGJA. We found that MTHFR rs1801133
      G>A polymorphism was significantly associated with the risk of developing EGJA
      (AA vs. GG: adjusted P = 0.001; GA/AA vs. GG: adjusted P = 0.007 and AA vs.
      GA/GG: adjusted P = 0.001). However, for MTHFR rs4845882 G>A polymorphism, the
      decreased risk of EGJA was found in two genetic models (AA vs. GG: adjusted P =
      0.002 and AA vs. GA/GG: adjusted P = 0.005). In addition, for MTHFR rs3753584 T>C
      and rs9651118 T>C polymorphisms, a tendency to decreased risk of EGJA was noted.
      In a subgroup analysis, a significantly decreased risk of EGJA in <64 years
      subgroup was identified. We found that MTHFR
      Grs1801133Trs3753584Grs4845882Ars4846048Crs9651118,
      Grs1801133Crs3753584Ars4845882Ars4846048Trs9651118 and
      Grs1801133Trs3753584Ars4845882Grs4846048Trs9651118 haplotypes significantly
      decreased the risk of EGJA (P = 0.002, P < 0.001 and P = 0.038, respectively). In
      conclusion, our study demonstrates that MTHFR rs1801133 G>A may be associated
      with the increased risk of EGJA. Meanwhile, MTHFR rs3753584 T>C, rs4845882 G>A
      and rs9651118 T>C polymorphisms and haplotypes may decrease the risk of EGJA in
      Eastern Chinese Han population. Further studies with large sample size and
      detailed gene-environmental data are needed to validate our conclusion.

PMID- 29340070
TI  - A novel orally available Syk/Src/Jak2 inhibitor, SKLB-850, showed potent anti
      tumor activities in B cell lymphoma (BCL) models.
AB  - B cell lymphoma (BCL) is the most frequently diagnosed type of non-Hodgkin
      lymphoma (NHL), and accounts for about 4% of all cancers in the USA. Kinases
      spleen tyrosine kinase (Syk), Src, and Janus kinase 2 (JAK2) have been thought as
      potential targets for the treatment of BCL. We have recently developed a
      multikinase inhibitor, SKLB-850, which potently inhibits Syk, Src, and JAK2. The
      aim of this study is to investigate the anti-BCL activities and mechanisms of
      action of SKLB-850 both in vitro and in vivo. Our results showed that SKLB-850
      significantly inhibited BCL cell proliferation, and induced apoptosis of BCL
      cells. It could considerably decrease the secretion of chemokines CCL3, CCL4, and
      CXCL12. Oral administration of SKLB-850 considerably suppressed the tumor growth
      in BCL xenograft models (Ramos and HBL-1) in a dose-dependent manner.
      Immunohistochemistry of tumor tissues showed that SKLB-850 efficiently inhibited
      the activation of Syk/ERK, Src/FAK and JAK2/Stat3 pathways. Collectively, SKLB
      850 could be a promising agent for the treatment of BCL, hence deserving further
      study.

PMID- 29340071
TI  - Hypoxia-inducible factor-1alpha regulates microglial functions affecting neuronal
      survival in the acute phase of ischemic stroke in mice.
AB  - Cells universally adapt to ischemic conditions by turning on a transcription
      factor hypoxia-inducible factor (HIF), in which its role is known to differ
      widely across many different types of cells. Given that microglia have been
      reported as an essential mediator of neuroinflammation in many brain diseases, we
      examined the role of HIF in microglia in the progression of an acute phase of
      ischemic stroke by challenging our novel strains of myeloid-specific Hif-1alpha
      or Hif-2alpha knockout (KO) mice created by Cre-loxP system via middle cerebral
      artery occlusion (MCAO). We observed that Hif-1alpha but not Hif-2alpha KO mice
      exhibited an improved recovery compared to wild-type (WT) mice determined by
      behavioral tests. Immunostaining analyses revealed that there were increased
      numbers of both mature and immature neurons while microglia and apoptotic cells
      were significantly decreased in the dentate gyrus of Hif-1alpha KO mice following
      MCAO. By isolating microglia with fluorescence-activated cell sorter, we found
      that HIF-1alpha-deficient microglia were impaired in phagocytosis, reactive
      oxygen species (ROS) production, and tumor necrosis factor-alpha (TNF-alpha)
      secretion. We further observed a significant decrease in the expression of Cd36
      and milk fat globule-epidermal growth factor 8 (Mfg-e8) genes, both of which
      contain hypoxia-responsive element (HRE). Knocking down either of these genes in
      BV2 microglial cells was sufficient to abrogate HIF-mediated increase in
      phagocytosis, production of intracellular ROS, or TNF-alpha secretion. Our
      results therefore suggest that HIF-1alpha in microglia is a novel therapeutic
      target to protect neuronal survival following an acute phase of ischemic stroke.

PMID- 29340072
TI  - Hyperbaric oxygen protects against myocardial reperfusion injury via the
      inhibition of inflammation and the modulation of autophagy.
AB  - Our previous study demonstrated that hyperbaric oxygen (HBO) preconditioning
      protected against myocardial ischemia reperfusion injury (MIRI) and improved
      myocardial infarction. However, HBO's effect on MIRI-induced inflammation and
      autophagy remains unclear. In this study, we investigate the potential impact and
      underlying mechanism of HBO preconditioning on an MIRI-induced inflammatory
      response and autophagy using a ligation of the left anterior descending (LAD)
      coronary artery rat model. Our results showed that HBO restored myocardial enzyme
      levels and decreased the apoptosis of cardiomyocytes, which were induced by MIRI.
      Moreover, HBO significantly suppressed MIRI-induced inflammatory cytokines. This
      effect was associated with the inhibition of the TLR4-nuclear factor kappa-B (NF
      kappaB) pathway. Interestingly, lower expression levels of microtubule-associated
      protein 1 light chain 3B (LC3B) and Beclin-1 were observed in the HBO-treatment
      group. Furthermore, we observed that HBO reduced excessive autophagy by
      activating the mammalian target of the rapamycin (mTOR) pathway, as evidenced by
      higher expression levels of threonine protein kinase (Akt) and phosphorylated
      mTOR. In conclusion, HBO protected cardiomocytes during MIRI by attenuating
      inflammation and autophagy. Our results provide a new mechanistic insight into
      the cardioprotective role of HBO against MIRI.

PMID- 29340073
TI  - YM155 exerts potent cytotoxic activity against quiescent (G0/G1) multiple myeloma
      and bortezomib resistant cells via inhibition of survivin and Mcl-1.
AB  - YM155, a novel small molecule inhibitor of survivin, shows broad anticancer
      activity. Here, we have focused on the cytotoxic activity of YM155 against
      multiple myeloma (MM) including cytokinetically quiescent (G0/G1) cells and
      bortezomib resistant cells. YM155 strongly inhibited the growth of MM cell lines
      with the IC50 value of below 10 nM. YM155 also showed potent anti-myeloma
      activity in mouse xenograft model. YM155 suppressed the expression of survivin
      and rapidly directed Mcl-1 protein for proteasome degradation. YM155 abrogated
      the interleukin-6-induced STAT3 phosphorylation, subsequently blocked Mcl-1
      expression and induced apoptosis in MM cells. Triple-color flow cytometric
      analysis revealed that YM155 potently induced cell death of MM cells in G0 phase.
      Quiescent primary MM cells were also sensitive to YM155. We established
      bortezomib-resistant MM cell line, U266/BTZR1, which possess a point mutation
      G322A. YM155 exhibited similar cytotoxic potency against U266/BTZR1 compared with
      parental cells. Interestingly, survivin expression was markedly elevated in
      U266/BTZR1 cells. Treatment with YM155 significantly down-regulated this
      increased survivin and Mcl-1 expression in U266/BTZR1 cells. In conclusion, our
      data indicate that YM155 exhibits potent cytotoxicity against quiescent (G0/G1)
      MM cells and bortezomib-resistant cells. These unique features of YM155 may be
      beneficial for the development of new therapeutic strategies to eliminate
      quiescent MM cells and overcome bortezomib resistance.

PMID- 29340074
TI  - Identification of novel diagnostic biomarkers for thyroid carcinoma.
AB  - Thyroid carcinoma (THCA) is the most universal endocrine malignancy worldwide.
      Unfortunately, a limited number of large-scale analyses have been performed to
      identify biomarkers for THCA. Here, we conducted a meta-analysis using 505 THCA
      patients and 59 normal controls from The Cancer Genome Atlas. After identifying
      differentially expressed long non-coding RNA (lncRNA) and protein coding genes
      (PCG), we found vast difference in various lncRNA-PCG co-expressed pairs in THCA.
      A dysregulation network with scale-free topology was constructed. Four molecules
      (LA16c-380H5.2, RP11-203J24.8, MLF1 and SDC4) could potentially serve as
      diagnostic biomarkers of THCA with high sensitivity and specificity. We further
      represent a diagnostic panel with expression cutoff values. Our results
      demonstrate the potential application of those four molecules as novel
      independent biomarkers for THCA diagnosis.

PMID- 29340075
TI  - Extracting microtentacle dynamics of tumor cells in a non-adherent environment.
AB  - During metastasis, tumor cells dynamically change their cytoskeleton to traverse
      through a variety of non-adherent microenvironments, including the vasculature or
      lymphatics. Due to the challenges of imaging drift in non-adhered tumor cells,
      the dynamic cytoskeletal phenotypes are poorly understood. We present a new
      approach to analyze the dynamic cytoskeletal phenotypes of non-adhered cells that
      support microtentacles (McTNs), which are cell surface projections implicated in
      metastatic reattachment. Combining a recently-developed cell tethering method
      with a novel image analysis framework allowed McTN attribute extraction. Full
      cell outlines, number of McTNs, and distance of McTN tips from the cell body
      boundary were calculated by integrating a rotating anisotropic filtering method
      for identifying thin features with retinal segmentation and active contour
      algorithms. Tethered cells behave like free-floating cells; however tethering
      reduces cell drift and improves the accuracy of McTN measurements. Tethering
      cells does not significantly alter McTN number, but rather allows better
      visualization of existing McTNs. In drug treatment experiments, stabilizing
      tubulin with paclitaxel significantly increases McTN length, while destabilizing
      tubulin with colchicine significantly decreases McTN length. Finally, we quantify
      McTN dynamics by computing the time delay autocorrelations of 2 composite
      phenotype metrics (cumulative McTN tip distance, cell perimeter:cell body ratio).
      Our automated analysis demonstrates that treatment with paclitaxel increases
      total McTN amount and colchicine reduces total McTN amount, while paclitaxel also
      reduces McTN dynamics. This analysis method enables rapid quantitative
      measurement of tumor cell drug responses within non-adherent microenvironments,
      using the small numbers of tumor cells that would be available from patient
      samples.

PMID- 29340076
TI  - Mitochondrial ROS activates ERK/autophagy pathway as a protected mechanism
      against deoxypodophyllotoxin-induced apoptosis.
AB  - Deoxypodophyllotoxin (DPT) is a naturally occurring flavolignan isolated from
      Anthriscus sylvestris. Recently, it has been reported that DPT inhibits tubulin
      polymerization and induces G2/M cell cycle arrest followed by apoptosis through
      multiple cellular processes. Despite these findings, details regarding the
      cellular and molecular mechanisms underlying the DPT-mediated cell death have
      been poorly understood. To define a mechanism of DPT-mediated cell death
      response, we examined whether DPT activates signaling pathways for autophagy and
      apoptosis. We demonstrated that DPT inhibited cell viability and induced
      apoptosis in prostate cancer cell lines, as evidenced by a mitochondrial membrane
      potential and expression of apoptosis-related proteins. Reactive oxygen species
      (ROS), primarily generated from the mitochondria, play an important role in
      various cellular responses, such as apoptosis and autophagy. DPT significantly
      triggered mitochondrial ROS, which were detected by MitoSOX, a selective
      fluorescent dye of mitochondria-derived ROS. Furthermore, DPT induced autophagy
      through an up-regulation of autophagic biomarkers, including a conversion of
      microtubule-associated protein 1 light chain 3 - I (LC3-I) into LC3-II and a
      formation of acidic vesicular organelles. Moreover, mitochondrial ROS promoted
      AKT-independent autophagy and ERK signaling. The inhibition of autophagy with 3
      methyladenine or LC3 knockdown enhanced DPT-induced apoptosis, suggesting that an
      autophagy plays a protective role in cell survival against apoptotic prostate
      cancer cells. Additionally, the results from an in vivo xenograft model confirmed
      that DPT inhibited tumor growth by regulating the apoptosis- and autophagy
      related proteins.

PMID- 29340077
TI  - LRP6 targeting suppresses gastric tumorigenesis via P14ARF-Mdm2-P53-dependent
      cellular senescence.
AB  - NLRP6, a member of the Nod-like receptor family, protects against chemically
      induced intestinal injury and colitis-associated colon cancer. However, the
      cellular mechanisms involved in this NLRP6-mediated protection remain unclear.
      Here, we show that NLRP6 was down-regulated in approximately 75% of primary
      gastric cancer cases and exhibited significant associations with advanced
      clinical-stage lymph node metastasis and poor overall survival. Functional
      studies established that ectopic overexpression or down-regulation of NLRP6
      inhibited cancer cell proliferation by inducing cell cycle arrest at the G1 phase
      via P21 and Cyclin D1 both in vitro and in vivo. Activation of the P14ARF-P53
      pathway played a crucial role in the observed cellular senescence. We further
      demonstrated that ectopic overexpression of NLRP6 combined with inactivation of
      NF-kappaB(p65) and Mdm2 activates P14ARF-P53 to promote the senescence of gastric
      cancer cells. These findings indicate that NLRP6 functions as a negative
      regulator of gastric cancer and offer a potential new option for preventing
      gastric cancer.

PMID- 29340078
TI  - Differential gene expression profiles between two subtypes of ischemic stroke
      with blood stasis syndromes.
AB  - Ischemic stroke is a cerebrovascular thrombotic disease with high morbidity and
      mortality. Qi deficiency blood stasis (QDBS) and Yin deficiency blood stasis
      (YDBS) are the two major subtypes of ischemic stroke according to the theories of
      traditional Chinese medicine. This study was conducted to distinguish these two
      syndromes at transcriptomics level and explore the underlying mechanisms. Male
      rats were randomly divided into three groups: sham group, QDBS/MCAO group and
      YDBS/MCAO group. Morphological changes were assessed after 24 h of reperfusion.
      Microarray analysis with circulating mRNA was then performed to identify
      differential gene expression profile, gene ontology and pathway enrichment
      analyses were carried out to predict the gene function, gene co-expression and
      pathway networks were constructed to identify the hub biomarkers, which were
      further validated by western blotting and Tunel staining analysis. Three subsets
      of dysregulated genes were acquired, including 445 QDBS-specific genes, 490 YDBS
      specific genes and 1676 blood stasis common genes. Our work reveals for the first
      time that T cell receptor, MAPK and apoptosis pathway were identified as the hub
      pathways based on the pathway networks, while Nfkappab1, Egfr and Casp3 were
      recognized as the hub genes by co-expression networks. This research helps
      contribute to a clearer understanding of the pathological characteristics of
      ischemic stroke with QDBS and YDBS syndrome, the proposed biomarkers might
      provide insight into the accurate diagnose and proper treatment for ischemic
      stroke with blood stasis syndrome.

PMID- 29340079
TI  - High expression of angiogenic factor AGGF1 is an independent prognostic factor
      for hepatocellular carcinoma.
AB  - Background: Angiogenesis plays a critical role in tumor growth and metastasis.
      Angiogenic factor with G patch and FHA domains 1 (AGGF1) has been recently
      identified as a novel initiator of angiogenesis. However, the function and the
      prognostic values of AGGF1 in hepatocellular carcinoma remain poorly understood.
      Our aim is to provide more information to assist design the angiogenesis therapy
      that targets AGGF1 in HCC. Results: AGGF1-positive frequency in HCC tissues was
      significantly higher than in peritumor tissues. The high expression of AGGF1
      expression in HCC tissue was well associated with the increased expression of
      VEGF and the high microvessel density (MVD). AGGF1 expression predicts a poor
      prognosis and AGGF1 was an independent prognostic factor for DFS. Methods: The
      expression levels of AGGF1, vascular endothelial growth factor (VEGF) and
      microvessel density (MVD) were identified by immunohistochemistry in 79 HCC tumor
      tissues and 24 corresponding peritumor tissues. The expression level of AGGF1 and
      MVD were quantified by counting the positively stained endothelial cells in the
      HCC and the peritumor tissue on the immunohistochemically stained tissue slides.
      The prognostic value of AGGF1 was evaluated by survival analysis. Conclusions:
      Our study shows that AGGF1 is identified as the independent prognostic factor for
      the disease-free survival (DFS) of patients after the surgical resection.
      contribute to tumor angiogenesis in HCC, which indicates that AGGF1 may be a new
      potential therapeutic target for anti-angiogenesis treatment for patients with
      HCC.

PMID- 29340080
TI  - Inhibition of tumor necrosis factor signaling attenuates renal immune cell
      infiltration in experimental membranous nephropathy.
AB  - Idiopathic membranous nephropathy (MN) is an autoimmune-mediated
      glomerulonephritis and the most common cause of idiopathic nephrotic syndrome in
      adult humans. A tumor necrosis factor alpha (TNF-alpha)-mediated inflammatory
      response via TNF receptor 1 (TNFR1) and TNFR2 has been proposed as a pathogenic
      factor. In this study, we assessed the therapeutic response to blocking TNF
      signaling in experimental MN. Murine MN was induced experimentally by cationic
      bovine serum albumin (cBSA); phosphate-buffered saline was used in control mice.
      In MN mice, TNF was inhibited by etanercept blocking of TNFR1/TNFR2 or the
      preligand assembly domain fusion protein (PLAD.Fc), a small fusion protein that
      can preferentially block TNFR1 signaling. Disease severity and possible
      mechanisms were assessed by analyzing the metabolic and histopathology profiles,
      lymphocyte subsets, immunoglobulin production, oxidative stress, and apoptosis.
      cBSA-induced MN mice exhibited typical nephrotic syndrome and renal
      histopathology. MN mice given etanercept or PLAD.Fc did not exhibit significant
      reduction of proteinuria, amelioration of glomerular lesions, or attenuation of
      immune complex deposition. Immune cell subsets, serum immunoglobulin levels,
      production of reactive oxygen species, and cell apoptosis in the kidney were not
      altered by TNF inhibition. By contrast, MN mice receiving etanercept or PLAD.Fc
      exhibited significantly decreased infiltration of immune cells into the kidney.
      These results show that the therapeutic effects of blocking TNFR1 and/or TNFR2
      signaling in experimental MN are not clinically effective. However, TNF signaling
      inhibition significantly attenuated renal immune cell infiltration in
      experimental MN.

PMID- 29340081
TI  - PCPA protects against monocrotaline-induced pulmonary arterial remodeling in
      rats: potential roles of connective tissue growth factor.
AB  - The purpose of this study was to investigate the mechanism of monocrotaline (MCT)
      induced pulmonary artery hypertension (PAH) and determine whether 4-chloro-DL
      phenylalanine (PCPA) could inhibit pulmonary arterial remodeling associated with
      connective tissue growth factor (CTGF) expression and downstream signal pathway.
      MCT was administered to forty Sprague Dawley rats to establish the PAH model.
      PCPA was administered at doses of 50 and 100 mg/kg once daily for 3 weeks via
      intraperitoneal injection. On day 22, the pulmonary arterial pressure (PAP),
      right ventricle hypertrophy index (RVI) and pulmonary artery morphology were
      assessed and the serotonin receptor-1B (SR-1B), CTGF, p-ERK/ERK were measured by
      western blot or immunohistochemistry. The concentration of serotonin in plasma
      was checked by ELISA. Apoptosis and apoptosis-related indexes were detected by
      TUNEL and western blot. In the MCT-induced PAH models, the PAP, RVI, pulmonary
      vascular remodeling, SR-1B index, CTGF index, anti-apoptotic factors bcl-xl and
      bcl-2, serotonin concentration in plasma were all increased and the pro-apoptotic
      factor caspase-3 was reduced. PCPA significantly ameliorated pulmonary arterial
      remodeling induced by MCT, and this action was associated with accelerated
      apoptosis and down-regulation of CTGF, SR-1B and p-ERK/ERK. The present study
      suggests that PCPA protects against the pathogenesis of PAH by suppressing
      remodeling and inducing apoptosis, which are likely associated with CTGF and
      downstream ERK signaling pathway in rats.

PMID- 29340082
TI  - Reciprocal sensitivity of diffuse large B-cell lymphoma cells to Bcl-2 inhibitors
      BIRD-2 versus venetoclax.
AB  - Bcl-2 is often upregulated in cancers to neutralize the BH3-only protein Bim at
      the mitochondria. BH3 mimetics (e.g. ABT-199 (venetoclax)) kill cancer cells by
      targeting Bcl-2's hydrophobic cleft and disrupting Bcl-2/Bim complexes. Some
      cancers with elevated Bcl-2 display poor responses towards BH3 mimetics,
      suggesting an additional function for anti-apoptotic Bcl-2 in these cancers.
      Indeed, Bcl-2 via its BH4 domain prevents cytotoxic Ca2+ release from the
      endoplasmic reticulum (ER) by directly inhibiting the inositol 1,4,5
      trisphosphate receptor (IP3R). The cell-permeable Bcl-2/IP3R disruptor-2 (BIRD-2)
      peptide can kill these Bcl-2-dependent cancers by targeting Bcl-2's BH4 domain,
      unleashing pro-apoptotic Ca2+-release events. We compared eight "primed to death"
      diffuse large B-cell lymphoma cell lines (DLBCL) for their apoptotic sensitivity
      towards BIRD-2 and venetoclax. By determining their IC50 using cytometric cell
      death analysis, we discovered a reciprocal sensitivity towards venetoclax versus
      BIRD-2. Using immunoblotting, we quantified the expression levels of IP3R2 and
      Bim in DLBCL cell lysates, revealing that BIRD-2 sensitivity correlated with
      IP3R2 levels but not with Bim levels. Moreover, the requirement of intracellular
      Ca2+ for BIRD-2- versus venetoclax-induced cell death was different. Indeed,
      BAPTA-AM suppressed BIRD-2-induced cell death, but promoted venetoclax-induced
      cell death in DLBCL cells. Finally, compared to single-agent treatments,
      combining BIRD-2 with venetoclax synergistically enhanced cell-death induction,
      correlating with a Ca2+-dependent upregulation of Bim after BIRD-2 treatment. Our
      findings suggest that some cancer cells require Bcl-2 proteins at the
      mitochondria, preventing Bax activation via its hydrophobic cleft, while others
      require Bcl-2 proteins at the ER, preventing cytotoxic Ca2+-signaling events via
      its BH4 domain.

PMID- 29340083
TI  - Next-generation sequencing-based microRNA profiling of mice testis subjected to
      transient heat stress.
AB  - This study aimed to investigate the role of microRNA (miRNA) in heat stress
      induced spermatogenic impairment. Testes from 15 adult ICR mice subjected to
      testicular hyperthermia at 43 degrees C for 30 min and from 15 control mice were
      collected and pooled into 3 samples. Isolated RNA from these samples was
      subjected to small RNA high-throughput sequencing, and differentially expressed
      miRNAs were identified and validated using RT-PCR. The identified miRNAs were
      further subjected to Gene Ontology and KEGG analyses, which revealed significant
      enrichment for pathways potentially involved in heat stress-induced spermatogenic
      impairment. Additionally, a correlation analysis of the relative levels of
      validated miRNAs with germ cell apoptosis was performed. Of the 11 miRNAs
      identified as differentially expressed, 8 were validated as consistent with
      sequencing data. Further analyses suggested that the target genes of those miRNAs
      were involved in various pathways (e.g., ribosomal, HIF-1, MAPK) that may be
      critical to heat stress-induced testicular damage. Some identified miRNAs,
      including miR-449a-3p, miR-92a-1-5p, miR-423-3p, and miR-128-3p, correlated
      closely with germ cell apoptosis. The study results reveal a detailed miRNA
      profile of heat stress-induced testicular damage and highlight new and
      potentially important candidate targets in the process of male infertility.

PMID- 29340084
TI  - CRISPR-Cas9 HDR system enhances AQP1 gene expression.
AB  - Ionizing radiation (IR) isthe primarytherapeutic tool to treat patients with
      cancerous lesions located in the head and neck. In many patients, IR results in
      irreversible and severe salivary gland dysfunction or xerostomia. Currently there
      are no effective treatment options to reduce the effects of xerostomia. More
      recently, salivary gland gene therapy utilizing the water-specific protein
      aquaporin 1 (AQP1) has been of great interest to potentially correct salivary
      dysfunction. In this study, we used CRISPR-Cas9 gene editing along with the
      endogenous promoter of AQP1 within theHEK293 and MDCK cell lines. The successful
      integration of the cytomegalovirus (CMV) promoterresultedin a significant
      increase of AQP1 gene transcription and translation. Additionalfunctional
      experiments involvingthe MDCK cell line confirmedthat over-expressed
      AQP1increasedtransmembrane fluid flux indicative of increased intracellular fluid
      flux. The off-target effect of designed guided RNA sequence was analyzed and
      demonstrateda high specificity for the Cas9 cleavage. Considering the development
      of new methods for robust DNA knock-in, our results suggest that endogenous
      promoter replacement may be a potential treatment forsalivary gland dysfunction.

PMID- 29340085
TI  - 6-(Methylsulfonyl) hexyl isothiocyanate as potential chemopreventive agent:
      molecular and cellular profile in leukaemia cell lines.
AB  - Numerous laboratory and epidemiological studies show that the risk of developing
      several types of cancer can be reduced with the employment of natural substances
      that act with multiple mechanisms. In this context, an important role is played
      by the isothiocyanates. Recently, 6-(methylsulfonyl)hexyl isothiocyanate (6
      MITC), present in the root of Wasabia Japonica, has stimulated the interest of
      researchers as a chemopreventive agent. In this particular study we have focused
      on evaluating 6-MITC's in vitro cytotoxic, cytostatic and cytodifferentiating
      activities, as well as its pro-apoptotic potential. These effects were
      investigated by way of flow cytometric analysis of Jurkat and HL-60 cells as well
      as of healthy lymphocytes extracted from the blood of AVIS donors, in order to
      verify a potential selectivity of action. The results demonstrate that 6-MITC
      exerts a stronger cytotoxic effect on tumour cells than on healthy cells. The
      apoptosis induction exerted by 6-MITC on transformed cells is triggered by an
      extrinsic pathway, as demonstrated by the statistically significant increase in
      the percentage of cells with activated caspase-8. It was also observed that 6
      MITC is able to limit tumour growth by slowing down and blocking the cell cycle
      of Jurkat and HL-60 cells respectively, in a dose- and time-related manner, while
      exerting no activity of any kind on the replication of healthy cells. Finally, by
      measuring the expression levels of CD-14 and CD-15, 6-MITC showed the ability to
      induce cytodifferentiation of HL-60 cells into macrophage and granulocytic
      phenotypes.

PMID- 29340086
TI  - Up-regulation of lncRNA SNHG1 indicates poor prognosis and promotes cell
      proliferation and metastasis of colorectal cancer by activation of the Wnt/beta
      catenin signaling pathway.
AB  - Recently, the lncRNA small nucleolar RNA host gene (SNHG1) has been exhibited to
      be upregulated, which plays a crucial role in the development and prognosis of
      several cancers. However, the role of the biology and clinical significance of
      SNHG1 in the tumorigenesis of colorectal cancer (CRC) has rarely been reported.
      In this work, we firstly found that SNHG1 expression levels were upregulated
      aberrantly in colorectal cancer tissues and colorectal cancer cell lines. By
      Kaplan-Meier survival analysis, patients with high SNHG1 expression level had
      poorer overall survival (OS) and progression-free survival (PFS) than those with
      low SNHG1 expression. In multivariate analysis, increased SNHG1 expression was
      proved to be an independent unfavorable prognostic indicator for CRC. In vitro
      experiments revealed that SNHG1 silencing inhibited the growth and metastasis and
      induced apoptosis of CRC cell lines. Finally, we found that SNHG1 may induce the
      activation of the WNT/beta-catenin pathway through regulating beta-catenin
      expression and transcription factor-4 (TCF-4), cyclin D1 and MMP-9. Altogether,
      our findings demonstrated that lncRNA SNHG1, was high expressed in colorectal
      cancer tissues and may serve as a tumor oncogene through regulating WNT/beta
      catenin signal pathway, which provided a candidate diagnostic biomarker and a
      promising therapeutic target for patients with CRC.

PMID- 29340087
TI  - Identification of antipsychotic drug fluspirilene as a potential anti-glioma stem
      cell drug.
AB  - Glioma stem cell (GSC)-targeted therapy is expected to be one of the most
      innovative approaches to treat patients with glioblastoma (GBM). A number of the
      drugs that restrain the signaling pathway essential for GSC maintenance have been
      under clinical trials. Here, we identified fluspirilene, a traditional
      antipsychotic drug, as a GSC-targeting agent, selected from thousands of existing
      drugs, and investigated its therapeutic effects against GBM with the purpose of
      drug repositioning. To develop novel therapeutics targeting GSCs, we initially
      screened drug libraries for small-molecule compounds showing a greater efficacy,
      compared to that of controls, in inhibiting the proliferation and survival of
      different GSC lines using cell proliferation assay. Drugs already reported to
      show therapeutic effects against GBM or those under clinical trials were excluded
      from subsequent screening. Finally, we found three drugs showing remarkable
      antiproliferative effects on GSCs at low concentrations and investigated their
      therapeutic effects on GSCs, glioma cell lines, and in a GBM mouse model. Of the
      three compounds, fluspirilene demonstrated a significant inhibitory effect on the
      proliferation and invasion of glioma cells as well as in the model mice treated
      with the drug. These effects were associated with the inactivation of the signal
      transducer and activator of transcription 3 (STAT3). Redeveloping of fluspirilene
      is a promising approach for the treatment of GBM.

PMID- 29340088
TI  - Identification of bladder cancer prognostic biomarkers using an ageing gene
      related competitive endogenous RNA network.
AB  - Competitive endogenous RNAs (ceRNAs) are a newly proposed RNA interaction
      mechanism that has been associated with the initiation and progression of various
      cancers. In this study, we constructed an ageing gene related ceRNA network
      (AgeingCeNet) in bladder cancer. Network analysis revealed that ageing gene
      ceRNAs have a larger degree and closeness centrality than ageing genes
      themselves. Notably, the difference of betweenness centrality of ageing genes and
      their ceRNAs is not significant, suggesting that the ceRNAs of ageing genes and
      ageing genes themselves both play important communication roles in AgeingCeNet.
      KEGG pathway enrichment analysis for genes in AgeingCeNet revealed that
      AgeingCeNet genes are enriched in cancer pathways and several cancer related
      singaling pathways. We also identified 37 core modules from AgeingCeNet using
      CFinder software. Next, we identified 2 potential prognostic modules, named
      K11M14 and K13M4, whose prognostic ability is better than that of age and gender.
      Finally, we identified microRNAs (miRNAs) regulating the two modules, which
      include miR-15b-5p, miR-195-5p, miR-30 family members, and several other cancer
      related miRNAs. Our study demonstrated that constructing an ageing gene related
      ceRNA network is a feasible strategy to explore the mechanism of initiation and
      progression of bladder cancer, which might benefit the treatment of this disease.

PMID- 29340089
TI  - LncRNA RNCR3 promotes Chop expression by sponging miR-185-5p during MDSC
      differentiation.
AB  - Myeloid-derived suppressor cells (MDSCs) play a critical role in regulating
      immune responses in cancer and other pathological conditions. Mechanism(s)
      regulating MDSC differentiation and function is not completely clear, especially
      epigenetic regulation. In this study, we found that MDSCs express retinal non
      coding RNA3 (RNCR3), and the expression in MDSCs is upregulated by inflammatory
      and tumor associated factors. RNCR3 may function as a competing endogenous RNA
      (ceRNA) to promote Chop expression by sponging miR-185-5p during MDSC
      differentiation. RNCR3 knockdown suppressed differentiation and function of MDSCs
      in vitro and in vivo. Quantitative RT-PCR showed that RNCR3 was negatively
      regulated by miR-185-5p in MDSCs. MiR-185-5p affected the expansion of MDSCs and
      reversed the effect of RNCR3 on MDSC differentiation and function through
      directly targeting Chop. Thus, our results suggest a RNCR3/miR-185-5p/Chop
      autologously strengthening network to promote MDSC differentiation and
      suppressive function in response to extracellular inflammatory and tumor
      associated signals.

PMID- 29340090
TI  - High glucose enhances the metastatic potential of tongue squamous cell carcinoma
      via the PKM2 pathway.
AB  - Previous evidence has indicated an increased cancer risk in individuals with
      diabetes mellitus (DM). The aim of this study was to investigate the relationship
      between DM (high glucose) and tongue squamous cell carcinoma (TSCC) and how high
      glucose mediated the metastatic potential of TSCC. The relationship between DM
      and TSCC was assessed in a retrospective study. The role and its mechanism of
      high glucose on the proliferation, metastatic potential of TSCC were investigated
      in vitro and in vivo. The prevalence rate of DM in patients with TSCC was 12.84%,
      which was significantly higher than that (9.7%) in the general population in
      China. Although no significant difference was observed in the overall survival
      (OS) rate, TSCC patients with DM have a 1.38-fold increase in relative risk
      affecting 5-year OS compared to patients without DM. High glucose enhanced the
      TSCC cell proliferation, migration, invasion and upregulated PKM2 (pyruvate
      kinase M2) expression. Whereas, these effect was abolished after knockdown of
      PKM2 in TSCC cells. High glucose promoted tumour growth and lung metastasis of
      TSCC in a DM animal model. Our results confirm DM as a risk factor for the
      development of TSCC. High glucose enhances the metastatic potential of TSCC
      through stimulation of the PKM2 pathway.

PMID- 29340091
TI  - Fatty acid binding protein 4 enhances prostate cancer progression by upregulating
      matrix metalloproteinases and stromal cell cytokine production.
AB  - Fatty acid binding protein 4 (FABP4) is an abundant protein in adipocytes, and
      its production is influenced by high-fat diet (HFD) or obesity. The prostate
      stromal microenvironment induces proinflammatory cytokine production, which is
      key for the development and progression of prostate cancer (PCa). Here, we show
      that high FABP4 expression and its secretion by PCa cells directly stimulated PCa
      cell invasiveness by upregulating matrix metalloproteinases through
      phosphatidylinositol 3-kinase and mitogen-activated protein kinase signaling
      pathways. In addition, prostate stromal cells augmented PCa cell invasiveness by
      secreting interleukin-8 and -6 in response to FABP4. This was abrogated by the
      FABP4 specific inhibitor, BMS309403. Furthermore, a mouse xenograft experiment
      showed HFD enhanced PCa metastasis and invasiveness by the upregulation of FABP4
      and interleukin-8. Clinically, the serum level of FABP4 was significantly
      associated with an aggressive type of PCa rather than obesity. Taken together,
      FABP4 may enhance PCa progression and invasiveness by upregulating matrix
      metalloproteinases and cytokine production in the PCa stromal microenvironment,
      especially under HFD or obesity.

PMID- 29340092
TI  - First-line dose-dense chemotherapy with docetaxel, cisplatin, folinic acid and 5
      fluorouracil (DCF) plus panitumumab in patients with locally advanced or
      metastatic cancer of the stomach or gastroesophageal junction: final results and
      biomarker analysis from an Italian oncology group for clinical research (GOIRC)
      phase II study.
AB  - Background: Survival for patients with advanced gastroesophageal cancer (AGC)
      using standard treatment regimens is poor. EGFR overexpression is common in AGC
      and associated with poor prognosis. We hypothesized that increasing the dose
      intensity of chemotherapy and adding panitumumab could improve efficacy. Methods:
      HER2 negative, PS 0-1 patients, received up to 4 cycles of panitumumab 6 mg/kg d
      1, docetaxel 60 mg/m2 d 1, cisplatin 50 mg/m2 d 1, l-folinic acid 100 mg/m2 d 1
      2, followed by 5-FU 400 mg/m2 bolus d 1-2, and then 600 mg/m2 as a 22 h c.i. on d
      1-2, q15 d, plus pegfilgrastim 6 mg on d 3. Patients with disease control after 4
      cycles received panitumumab until progression. Results: From 05/2010 to 01/2014,
      52 patients (75% male; median age 64.5 y; metastatic 90%, locally advanced 10%;
      96% adenocarcinoma; 25% GEJ) were recruited. Three CR, 29 PR, 10 SD and 8 PD were
      observed, for an ORR by ITT (primary endpoint) of 62% (95% CI, 48%-75%) and a DCR
      of 81%. Median TTP was 4.9 months (95% CI, 4.2-7.0) and mOS 10 months (95% CI,
      8.2- 13.5). Most frequent G3-4 toxicities: leucopenia (29%), asthenia (27%), skin
      rash (25%), neutropenia (19%), anorexia (17%), febrile neutropenia (13%), and
      diarrhea (15%). EGFR expression tested both with dd-PCR and FISH was not
      associated with any significant clinical benefit from treatment. Conclusions:
      Dose-dense DCF plus panitumumab is an active regimen. However, the toxicity
      profile of this limits further development. Further research on predictive
      biomarkers for treatment efficacy in AGC is required.Clinical trial information:
      2009-016962-10.

PMID- 29340093
TI  - Leucine mediates autophagosome-lysosome fusion and improves sperm motility by
      activating the PI3K/Akt pathway.
AB  - Amino acid supplementation is an efficient and effective strategy to increase
      sperm quality. In our research, a comparative study was conducted to screen free
      amino acids to improve sperm motility, and we found that leucine was the most
      efficient one. Leucine treatment increases sperm motility depending on the
      activation of PI3K/Akt signaling pathway, while the chemical inhibitor of
      PI3K/Akt signal could reduce the amount of pAkt activated by leucine treatment.
      Moreover, leucine treatment improved the expression of P62 and LC3-II,
      substantially suppressed the autophagy process in zebrafish testis. In vitro
      studies showed that leucine could reduce the fusion of autophagosome and lysosome
      that was indicated by the co-localization of EGFP-LC3 and lysosome marker. Two
      chemical modulators of autophagy, such as LY294002 (the inhibitor of PI3K/Akt
      signal) and chloroquine were administered to investigate the process of autophagy
      on zebrafish sperm motility. LY294002 inhibited autophagosome formation to
      reduced sperm motility, while chloroquine inhibited the fusion of autophagosome
      and lysosome to improve sperm motility. Our data suggest that short-term
      treatment with leucine could increase zebrafish sperm motility by affecting the
      autophagy and inhibiting the fusion of autophagosome and lysosomes, depending on
      the activation of PI3K/Akt signaling pathway.

PMID- 29340094
TI  - Can urologists introduce the concept of "oligometastasis" for metastatic bladder
      cancer after total cystectomy?
AB  - We investigated whether the concept of oligometastasis may be introduced to the
      clinical management of metastatic bladder cancer patients. Our study population
      comprised 128 patients diagnosed with metastatic bladder cancer after total
      cystectomy at our 6 institutions between 2004 and 2014. We extracted independent
      predictors for identifying a favorable. Occurrence that fulfilled all 4 criteria
      which were independently associated with cancer-specific death was defined as
      oligometastasis: a solitary metastatic organ; number of metastatic lesions of 3
      or less; the largest diameter of metastatic foci of 5cm or less; and no liver
      metastasis. We evaluated differences in clinical outcomes between patients with
      oligometastasis (oligometastasis group) and those without oligometastasis (non
      oligometastasis group). Overall, there were 43 patients in the oligometastasis
      group. The 2-year cancer-specific survival rate in the oligometastasis group was
      53.3%, which was significantly higher than that in the non-oligometastasis group
      (16.1%, p<0.001). A multivariate analysis revealed that non-oligometastasis
      (p<0.001), not performing salvage chemotherapy (p<0.001), and not performing
      metastatectomy (p=0.028) were independent risk factors for cancer-specific death.
      In the subgroup of 83 patients who received salvage chemotherapy, 30 were in the
      oligometastasis group. The 2-year cancer-specific survival rate in the
      oligometastasis group was 55.0%, which was significantly higher than that in the
      non-oligometastasis group (22.0%, p=0.005). Non-oligometastasis (p=0.009) was the
      only independent risk factor for cancer-specific death. We presented that
      urothelial carcinoma with oligometastasis had a favorable prognosis and responded
      to systemic chemotherapy. Oligometastasis may be treated as a separate entity in
      the field of metastatic urothelial carcinoma.

PMID- 29340095
TI  - Tumoral immune-infiltrate (IF), PD-L1 expression and role of CD8/TIA-1
      lymphocytes in localized osteosarcoma patients treated within protocol ISG-OS1.
AB  - Background: We hypothesized that immune-infiltrates were associated with superior
      survival, and examined a primary osteosarcoma tissue microarrays (TMAs) to test
      this hypothesis. Methods: 129 patients (pts) with localized osteosarcoma treated
      within protocol ISG-OS1 were included in the study. Clinical characteristics,
      expression of CD8, CD3, FOXP3, CD20, CD68/CD163 (tumor associated macrophage,
      TAM), Tia-1 (cytotoxic T cell), CD303 (plasmacytoid dendritic cells: pDC),
      Arginase-1 (myeloid derived suppressor cells: MDSC), PD-1 on immune-cells (IC),
      and PD-L1 on tumoral cells (TC) and IC were analysed and correlated with outcome.
      Results: Most of the cases presented tumor infiltrating lymphocytes (TILs) (CD3+
      90%; CD8+ 86%). Tia-1 was detected in 73% of the samples. PD-L1 expression was
      found in 14% patients in IC and 0% in TC; 22% showed PD-1 expression in IC.With a
      median follow-up of 8 years (range 1-13), the 5-year overall survival (5-year OS)
      was 74% (95% CI 64-85). Univariate analysis showed better 5-year OS for: a) pts
      with a good histologic response to neoadjuvant chemotherapy (p = 0.0001); b) pts
      with CD8/Tia1 tumoral infiltrates (p = 0.002); c) pts with normal alkaline
      phosphatas (sALP) (p = 0.04). After multivariate analysis, histologic response (p
      = 0.007) and CD8/Tia1 infiltration (p = 0.01) were independently correlated with
      survival. In the subset of pts with CD8+ infiltrate, worse (p 0.02) OS was
      observed for PD-L1(IC)+ cases. Conclusions: Our findings support the hypothesis
      that CD8/Tia1 infiltrate in tumor microenvironment at diagnosis confers superior
      survival for pts with localized osteosarcoma, while PD-L1 expression is
      associated with worse survival.

PMID- 29340097
TI  - S-adenosyl-methionine (SAM) alters the transcriptome and methylome and
      specifically blocks growth and invasiveness of liver cancer cells.
AB  - S-adenosyl methionine (SAM) is a ubiquitous methyl donor that was reported to
      have chemo- protective activity against liver cancer, however the molecular
      footprint of SAM is unknown. We show here that SAM selectively inhibits growth,
      transformation and invasiveness of hepatocellular carcinoma cell lines but not
      normal primary liver cells. Analysis of the transcriptome of SAM treated and
      untreated liver cancer cell lines HepG2 and SKhep1 and primary liver cells
      reveals pathways involved in cancer and metastasis that are upregulated in cancer
      cells and are downregulated by SAM. Analysis of the methylome using bisulfite
      mapping of captured promoters and enhancers reveals that SAM hyper-methylates and
      downregulates genes in pathways of growth and metastasis that are upregulated in
      liver cancer cells. Depletion of two SAM downregulated genes STMN1 and TAF15
      reduces cellular transformation and invasiveness, providing evidence that SAM
      targets are genes important for cancer growth and invasiveness. Taken together
      these data provide a molecular rationale for SAM as an anticancer agent.

PMID- 29340098
TI  - ICAM-1 regulates macrophage polarization by suppressing MCP-1 expression via miR
      124 upregulation.
AB  - Intercellular adhesion molecule-1 is the adhesion molecule mediating leukocyte
      firm adhesion to endothelial cells, plays a critical role in subsequent leukocyte
      transmigration. ICAM-1 is also expressed in other cells including macrophages;
      however, the role of this adhesion molecule in mediating macrophage functions
      remains enigmatic. We report that ICAM-1 regulates macrophage polarization by
      positively modulating miR-124 expression. We found higher expression levels of
      monocyte chemotactic protein-1 in lungs of mice lacking ICAM-1. Consistent with
      this result, siRNA mediated depletion of ICAM-1 in macrophage resulted in
      increased expression levels of MCP-1. Moreover, ICAM-1 controlled miR-124
      expression and downregulated MCP-1 mRNA and protein expression by binding of miR
      124 to MCP-1 3' untranslated region. ICAM-1 also induced the transcription factor
      Sp1 expression, which is important for miR-124 expressing in macrophages.
      Furthermore, ICAM-1 depletion led to M1 macrophage polarization, in contrast, miR
      124 mimics promoted M2 macrophage polarization. Exogenous administration of miR
      124 mimics into the lungs prevented lipopolysaccharide-induced myeloperoxidase
      activity in vivo, suggesting that miR-124 is important for dampening acute lung
      injury. These results collectively show that adhesion molecule ICAM-1
      downregulates MCP-1 expression by controlling Sp1 mediated miR-124 levels, which
      in turn regulate M2 macrophage polarization. Targeting ICAM-1 and downstream miR
      124 may present a new therapeutic strategy for acute lung injury.

PMID- 29340096
TI  - CRISPR/Cas9-mediated reversibly immortalized mouse bone marrow stromal stem cells
      (BMSCs) retain multipotent features of mesenchymal stem cells (MSCs).
AB  - Mesenchymal stem cells (MSCs) are multipotent non-hematopoietic progenitor cells
      that can undergo self-renewal and differentiate into multi-lineages. Bone marrow
      stromal stem cells (BMSCs) represent one of the most commonly-used MSCs. In order
      to overcome the technical challenge of maintaining primary BMSCs in long-term
      culture, here we seek to establish reversibly immortalized mouse BMSCs (imBMSCs).
      By exploiting CRISPR/Cas9-based homology-directed-repair (HDR) mechanism, we
      target SV40T to mouse Rosa26 locus and efficiently immortalize mouse BMSCs (i.e.,
      imBMSCs). We also immortalize BMSCs with retroviral vector SSR #41 and establish
      imBMSC41 as a control line. Both imBMSCs and imBMSC41 exhibit long-term
      proliferative capability although imBMSC41 cells have a higher proliferation
      rate. SV40T mRNA expression is 130% higher in imBMSC41 than that in imBMSCs.
      However, FLP expression leads to 86% reduction of SV40T expression in imBMSCs,
      compared with 63% in imBMSC41 cells. Quantitative genomic PCR analysis indicates
      that the average copy number of SV40T and hygromycin is 1.05 for imBMSCs and 2.07
      for imBMSC41, respectively. Moreover, FLP expression removes 92% of SV40T in
      imBMSCs at the genome DNA level, compared with 58% of that in imBMSC41 cells,
      indicating CRISPR/Cas9 HDR-mediated immortalization of BMSCs can be more
      effectively reversed than that of retrovirus-mediated random integrations.
      Nonetheless, both imBMSCs and imBMSC41 lines express MSC markers and are highly
      responsive to BMP9-induced osteogenic, chondrogenic and adipogenic
      differentiation in vitro and in vivo. Thus, the engineered imBMSCs can be used as
      a promising alternative source of primary MSCs for basic and translational
      research in the fields of MSC biology and regenerative medicine.

PMID- 29340099
TI  - A plasma miRNA signature for lung cancer early detection.
AB  - The early detection of lung cancer continues to be a major clinical challenge.
      Using whole-transcriptome next-generation sequencing to analyze lung tumor and
      the matched noncancerous tissues, we previously identified 54 lung cancer
      associated microRNAs (miRNAs). The objective of this study was to investigate
      whether the miRNAs could be used as plasma biomarkers for lung cancer. We
      determined expressions of the lung tumor-miRNAs in plasma of a development cohort
      of 180 subjects by using reverse transcription PCR to develop biomarkers. The
      development cohort included 92 lung cancer patients and 88 cancer-free smokers.
      We validated the biomarkers in a validation cohort of 64 individuals comprising
      34 lung cancer patients and 30 cancer-free smokers. Of the 54 miRNAs, 30
      displayed a significant different expression level in plasma of the lung cancer
      patients vs. cancer-free controls (all P < 0.05). A plasma miRNA signature (miRs
      126, 145, 210, and 205-5p) with the best prediction was developed, producing
      91.5% sensitivity and 96.2% specificity for lung cancer detection. Diagnostic
      performance of the plasma miRNA signature had no association with stage and
      histological type of lung tumor, and patients' age, sex, and ethnicity (all p >
      0.05). The plasma miRNA signature was reproducibly confirmed in the validation
      cohort. The plasma miRNA signature may provide a blood-based assay for diagnosing
      lung cancer at the early stage, and thereby reduce the associated mortality and
      cost.

PMID- 29340100
TI  - The inhibition of cordycepin on cancer stemness in TGF-beta induced chemo
      resistant ovarian cancer cell.
AB  - Chemotherapy is one of the main approach for ovarian cancer. Cancer stem cells
      (CSCs) escape chemotherapy and lead to chemoresistance. We previously
      demonstrated that cordycepin (Cd) inhibited metastasis in human ovarian carcinoma
      cells, the aim of this study is to investigate the effects of Cd on ovarian
      cancer stemness. TGF-beta was used to induce chemoresistance of chemotherapeutic
      agent cisplatin in SKOV-3 ovarian cancer cells. After treating with 100 MUM of
      Cd, cell viability, the percentage of cancer stem cells, and the levels of matrix
      metalloproteinases (MMPs) were decreased in TGF-beta-induced SKOV-3 cells.
      Treatment of Cd recovered E-cadherin levels and inhibited vimentin levels while
      TGF-beta treatment significantly increased the expression of vimentin and PGC
      1alpha, and decreased E-cadherin levels in SKOV-3 cells, indicating that the
      action of Cd on cancer stemness may contribute to the regulation of epithelial
      mesenchymal transition (EMT). Cd efficiently attenuated chemoresistance caused by
      TGF-beta in SKOV-3 cancer stem cells to promote the cytotoxicity of cisplatin.

PMID- 29340101
TI  - IGF-1 induces the epithelial-mesenchymal transition via Stat5 in hepatocellular
      carcinoma.
AB  - It has been reported that the epithelial-mesenchymal transition (EMT) plays an
      important role in hepatocellular carcinoma (HCC). However, the relationship
      between the insulin-like growth factor-1 (IGF-1) and EMT of HCC was not fully
      elucidated. In the present work, we found that the expression of N-cadherin,
      Vimentin, Snail1, Snail2, and Twist1 was positively associated with IGF-1R
      expression, while E-cadherin expression was negatively associated with IGF-1
      expression in human HCC samples. Furthermore, we observed that IGF-1 up-regulated
      the expression of N-cadherin, Vimentin, Snail1, Snail2 and Twist1, and down
      regulated the expression of E-cadherin. In addition, Stat5 was induced in IGF-1
      treated HepG2 and Hep3B cells, and Stat5 inhibition or siRNA significantly
      affected IGF-1-induced EMT in HepG2 and Hep3B cells. In conclusion, IGF-1 induces
      EMT of HCC via Stat5 signaling pathway. Thus, IGF-1/Stat5 can be recommended as a
      potential and novel therapeutic strategy for HCC patients.

PMID- 29340102
TI  - The impact of antibiotic usage on the efficacy of chemoimmunotherapy is
      contingent on the source of tumor-reactive T cells.
AB  - In recent years the combined use of chemotherapy and immunotherapy, collectively
      termed chemoimmunotherapy, has emerged as a promising treatment option for
      patients with cancer. Antibiotics are commonly used to reduce infection-related
      complications in patients undergoing chemotherapy. Intriguingly, accumulating
      evidence has implicated gut microbiota as a critical determinant of host
      antitumor immune responses, raising the question as to whether the use of broad
      spectrum antibiotics would invariably diminish tumor response to
      chemoimmunotherapies. We investigated the impact of antibiotics on the
      therapeutic outcomes of cyclophosphamide (CTX) chemotherapy and adoptive T-cell
      therapy (ACT) where CTX was used as the host-conditioning regimen in mice. We
      show that antibiotic prophylaxis dampened the endogenous T cell responses
      elicited by CTX, and reduced the efficacy of CTX against B-cell lymphoma. In the
      ACT setting, antibiotics administration impaired the therapeutic effects of
      adoptively transferred tumor-specific CD4+ T cells in mice with implanted
      colorectal tumors. In contrast, long-term antibiotic exposure did not affect the
      efficacy of ACT using CD19-targeting chimeric antigen receptor (CAR) T cells in
      mice with systemic B-cell lymphoma, although it correlated with prolonged CAR
      expression and sustained B-cell aplasia. Our study demonstrates that
      chemoimmunotherapies may have variable reliance on intestinal microbiota for T
      cell activation and function, and thus have different sensitivities to antibiotic
      prophylaxis. These findings may have implications for the judicial use of
      antibiotics in cancer patients receiving chemoimmunotherapies.

PMID- 29340103
TI  - Anti-neoplastic drugs increase caveolin-1-dependent migration, invasion and
      metastasis of cancer cells.
AB  - Expression of the scaffolding protein Caveolin-1 (CAV1) enhances migration and
      invasion of metastatic cancer cells. Yet, CAV1 also functions as a tumor
      suppressor in early stages of cancer, where expression is suppressed by
      epigenetic mechanisms. Thus, we sought to identify stimuli/mechanisms that revert
      epigenetic CAV1 silencing in cancer cells and evaluate how this affects their
      metastatic potential. We reasoned that restricted tissue availability of anti
      neoplastic drugs during chemotherapy might expose cancer cells to sub-therapeutic
      concentrations, which activate signaling pathways and the expression of CAV1 to
      favor the acquisition of more aggressive traits. Here, we used in vitro [2D,
      invasion] and in vivo (metastasis) assays, as well as genetic and biochemical
      approaches to address this question. Colon and breast cancer cells were
      identified where CAV1 levels were low due to epigenetic suppression and could be
      reverted by treatment with the methyltransferase inhibitor 5'-azacytidine.
      Exposure of these cells to anti-neoplastic drugs for short periods of time (24-48
      h) increased CAV1 expression through ROS production and MEK/ERK activation. In
      colon cancer cells, increased CAV1 expression enhanced migration and invasion in
      vitro via pathways requiring Src-family kinases, as well as Rac-1 activity.
      Finally, elevated CAV1 expression in colon cancer cells following exposure in
      vitro to sub-cytotoxic drug concentrations increased their metastatic potential
      in vivo. Therefore exposure of cancer cells to anti-neoplastic drugs at non
      lethal drug concentrations induces signaling events and changes in transcription
      that favor CAV1-dependent migration, invasion and metastasis. Importantly, this
      may occur in the absence of selection for drug-resistance.

PMID- 29340104
TI  - Somatic mutation dynamics in MDS patients treated with azacitidine indicate
      clonal selection in patients-responders.
AB  - Azacitidine (AZA) for higher risk MDS patients is a standard therapy with limited
      durability. To monitor mutation dynamics during AZA therapy we utilized massive
      parallel sequencing of 54 genes previously associated with MDS/AML pathogenesis.
      Serial sampling before and during AZA therapy of 38 patients (reaching median
      overall survival 24 months (Mo) with 60% clinical responses) identified 116
      somatic pathogenic variants with allele frequency (VAF) exceeding 5%. High
      accuracy of data was achieved via duplicate libraries from myeloid cells and T
      cell controls. We observed that nearly half of the variants were stable while
      other variants were highly dynamic. Patients with marked decrease of allelic
      burden upon AZA therapy achieved clinical responses. In contrast, early
      progressing patients on AZA displayed minimal changes of the mutation pattern. We
      modeled the VAF dynamics on AZA and utilized a joint model for the overall
      survival and response duration. While the presence of certain variants associated
      with clinical outcomes, such as the mutations of CDKN2A were adverse predictors
      while KDM6A mutations yield lower risk of dying, the data also indicate that
      allelic burden volatility represents additional important prognostic variable. In
      addition, preceding 5q- syndrome represents strong positive predictor of longer
      overall survival and response duration in high risk MDS patients treated with
      AZA. In conclusion, variants dynamics detected via serial sampling represents
      another parameter to consider when evaluating AZA efficacy and predicting
      outcome.

PMID- 29340105
TI  - Long-term effects of sitagliptin in patients with type 2 diabetes mellitus and
      hypertension: results from the PROLOGUE study.
AB  - Background: The effects of sitagliptin in patients with type 2 diabetes mellitus
      and hypertension are unclear. Therefore, we evaluated the long-term effects of
      sitagliptin in those patients. Methods: In the PROLOGUE study, 365 patients were
      diagnosed as type 2 diabetes mellitus and hypertension, and 189 patients in the
      sitagliptin group, 176 patients in the conventional group. Fasting blood glucose
      (FBG), HbA1c, systolic pressure (SP), diastolic pressure (DP), serum urea
      nitrogen (BUN) and serum creatinine (SCR) were measured at the beginning of the
      study and after 12 and 24 months of treatment. Results: FBS and HbA1c levels were
      not significantly decreased after treatment [12 months: OR: -3.1, 95% CI (-11.3,
      5.0); OR: 0.1, 95% CI (0.0, 0.3); 24 months: OR: -0.1, 95% CI (-9.1, 8.8); OR:
      0.1, 95% CI (0.0, 0.3), respectively]. BP and DP levels were not significantly
      decreased after treatment (12 months: OR: 0.9, 95% CI (-2.8, 4.6); OR: 0.6, 95%
      CI (-2.0, 3.2); 24 months: OR: -0.5, 95% CI (-4.2, 3.1); OR: -1.6, 95% CI (-41,
      0.9), respectively]. Furthermore, BUN and SCR levels were not significantly
      decreased after treatment (12 months: OR: 0.0, 95%CI (-1.2, 1.2); OR: 0.0, 95% CI
      (-0.1, 0.0); 24 months: OR: 0.4, 95% CI (-1.0, 1.8); OR: -80.8, 95% CI (-201.3,
      39.8), respectively]. After adjusting for confounding factors, our results did
      not change. Conclusions: In our study, there was no evidence that treatment with
      sitagliptin can improve FBS, BP, DP, BUN or SCR in patients with type 2 diabetes
      mellitus and hypertension. Trial Registration: University Hospital Medical
      Information Network Clinical Trials Registry UMIN000004490.

PMID- 29340106
TI  - A maternal high-fat diet during pregnancy and lactation, in addition to a
      postnatal high-fat diet, leads to metabolic syndrome with spatial learning and
      memory deficits: beneficial effects of resveratrol.
AB  - We tested the hypothesis that high-fat diet consumption during pregnancy,
      lactation, and/or post weaning, altered the expression of molecular mediators
      involved in hippocampal synaptic efficacy and impaired spatial learning and
      memory in adulthood. The beneficial effect of resveratrol was assessed. Dams were
      fed a rat chow diet or a high-fat diet before mating, during pregnancy, and
      throughout lactation. Offspring were weaned onto either a rat chow or a high-fat
      diet. Four experimental groups were generated, namely CC, HC, CH, and HH
      (maternal chow diet or high-fat diet; postnatal chow diet or high-fat diet). A
      fifth group fed with HH plus resveratrol (HHR) was generated. Morris water maze
      test was used to evaluate spatial learning and memory. Blood pressure and IPGTT
      was measured to assess insulin resistance. Dorsal hippocampal expression of
      certain biochemical molecules, including sirtuin 1, ERK, PPARgamma, adiponectin,
      and BDNF were measured. Rats in HH group showed impaired spatial memory, which
      was partly restored by the administration of resveratrol. Rats in HH group also
      showed impaired glucose tolerance and increased blood pressure, all of which was
      rescued by resveratrol administration. Additionally, SIRT1, phospho-ERK1/2, and
      phospho-PPARgamma, adiponectin and BDNF were all dysregulated in rats placed in
      HH group; administration of resveratrol restored the expression and regulation of
      these molecules. Overall, our results suggest that maternal high-fat diet during
      pregnancy and/or lactation sensitizes the offspring to the adverse effects of a
      subsequent high-fat diet on hippocampal function; however, administration of
      resveratrol is demonstrated to be beneficial in rescuing these effects.

PMID- 29340107
TI  - A comparison of ARMS-Plus and droplet digital PCR for detecting EGFR activating
      mutations in plasma.
AB  - In this study, we introduce a novel amplification refractory mutation system
      (ARMS)-based assay, namely ARMS-Plus, for the detection of epidermal growth
      factor receptor (EGFR) mutations in plasma samples. We evaluated the performance
      of ARMS-Plus in comparison with droplet digital PCR (ddPCR) and assessed the
      significance of plasma EGFR mutations in predicting efficacy of EGFR-tyrosine
      kinase inhibitor (TKI) regimen. A total of 122 advanced non-small cell lung
      cancer (NSCLC) patients were enrolled in this study. The tumor tissue samples
      from these patients were evaluated by conventional ARMS PCR method to confirm
      their EGFR mutation status. For the 116 plasma samples analyzed by ARMS-Plus, the
      sensitivity, specificity, and concordance rate were 77.27% (34/44), 97.22%
      (70/72), and 89.66% (104/116; kappa=0.77, P<0.0001), respectively. Among the 71
      plasma samples analyzed by both ARMS-Plus and ddPCR, ARMS-Plus showed a higher
      sensitivity than ddPCR (83.33% versus 70.83%). The presence of EGFR activating
      mutations in plasma was not associated with the response to EGFR-TKI, although
      further validation with a larger cohort is required to confirm the correlation.
      Collectively, the performance of ARMS-Plus and ddPCR are comparable. ARMS-Plus
      could be a potential alternative to tissue genotyping for the detection of plasma
      EGFR mutations in NSCLC patients.

PMID- 29340108
TI  - Effect of gene-lifestyle interaction on gestational diabetes risk.
AB  - We hypothesized that the association of certain lifestyle parameters with
      gestational diabetes mellitus (GDM) risk would depend on susceptibility loci. In
      total, 278 Russian women with GDM and 179 controls completed questionnaires about
      lifestyle habits (food consumption, physical activity and smoking). GDM was
      diagnosed according to the criteria of the International Association of Diabetes
      and Pregnancy Study Groups. Maternal blood was sampled for genotyping single
      nucleotide polymorphisms (SNPs) in MTNR1B (rs10830963 and rs1387153), GCK
      (rs1799884), KCNJ11 (rs5219), IGF2BP2 (rs4402960), TCF7L2 (rs7903146 and
      rs12255372), CDKAL1 (rs7754840), IRS1 (rs1801278) and FTO (rs9939609). Binary
      logistic regression revealed an interaction effect of sausage intake and the
      number of risk alleles of two SNPs (rs10830963 in MTNR1B and rs1799884 in GCK) on
      GDM risk (P < 0.001). Among women without risk alleles of these two SNPs, sausage
      consumption was positively associated with GDM risk (P trend = 0.045). This
      difference was not revealed in women carrying 1 or more risk alleles. The risk of
      GDM increased as the number of risk alles increased in participants with low and
      moderate sausage consumption (P trend <0.001 and 0.006, respectively), while the
      risk of GDM in women with high sausage consumption remained relatively high,
      independent of the number of risk alleles. These findings indicate that the
      association of sausage consumption with GDM risk can be determined based on the
      number of risk alleles of rs10830963 in MTNR1B and rs1799884 in GCK.

PMID- 29340110
TI  - Curcumin attenuates myocardial ischemia-reperfusion injury.
AB  - Background: Cardiovascular diseases (CVDs) are at a badly high-risk of morbidity
      and mortality in the world. Methods: Our study was attempted to investigate the
      cardioprotective role of curcumin. Hearts injury was assessed in isolated hearts
      and the rats of coronary artery ligated. Results and Conclusions: The inhibition
      of pro-inflammatory cytokines was observed by curcumin in coronary artery ligated
      rats. ST segment was also reduced by curcumin. Triphenyltetrazolium chloride
      staining (TTC) staining and pathological analysis were also showed that curcumin
      could dramatically alleviate myocardial injury. Besides, the results in vitro
      also demonstrated that curcumin could improved the function of isolated hearts.
      Besides, the expressions of inflammation-related pathway in both rats and
      isolated hearts treated with curcumin were significantly decreased. The present
      study investigated the protective effects of curcumin on myocardial injury and
      its mechanism.

PMID- 29340109
TI  - Development of a targeted sequencing approach to identify prognostic, predictive
      and diagnostic markers in paediatric solid tumours.
AB  - The implementation of personalised medicine in childhood cancers has been limited
      by a lack of clinically validated multi-target sequencing approaches specific for
      paediatric solid tumours. In order to support innovative clinical trials in high
      risk patients with unmet need, we have developed a clinically relevant targeted
      sequencing panel spanning 311 kb and comprising 78 genes involved in childhood
      cancers. A total of 132 samples were used for the validation of the panel,
      including Horizon Discovery cell blends (n=4), cell lines (n=15), formalin-fixed
      paraffin embedded (FFPE, n=83) and fresh frozen tissue (FF, n=30) patient
      samples. Cell blends containing known single nucleotide variants (SNVs, n=528)
      and small insertion-deletions (indels n=108) were used to define panel
      sensitivities of >=98% for SNVs and >=83% for indels [95% CI] and panel
      specificity of >=98% [95% CI] for SNVs. FFPE samples performed comparably to FF
      samples (n=15 paired). Of 95 well-characterised genetic abnormalities in 33
      clinical specimens and 13 cell lines (including SNVs, indels, amplifications,
      rearrangements and chromosome losses), 94 (98.9%) were detected by our approach.
      We have validated a robust and practical methodology to guide clinical management
      of children with solid tumours based on their molecular profiles. Our work
      demonstrates the value of targeted gene sequencing in the development of
      precision medicine strategies in paediatric oncology.

PMID- 29340111
TI  - Effect of dihydropyrimidine dehydrogenase single nucleotide polymorphisms on
      prognosis of breast cancer patients with chemotherapy.
AB  - Defining biomarkers that predict therapeutic effects and adverse events is a
      crucial mandate to guide patient selection for personalized cancer treatments.
      DPD (dihydropyrimidine dehydrogenase, encoded by DPYD gene) is the initial and
      rate-limiting enzyme of metabolic pathway of fluoropyrimidines, and
      fluoropyrimidines are common used drug therapies for breast cancer. Previous
      studies on DPYD polymorphism were mainly focused on its association with
      fluoropyrimidines toxicity. In our present study, 5 DPYD single nucleotide
      polymorphisms status was detected from tumor tissues of 331 invasive breast
      cancer patients using standard techniques. We for the first time investigated the
      prognostic significance of DPYD polymorphisms in breast cancer. We demonstrated
      non-luminal breast cancer patients carrying DPYD c.1627A>G AG/GG treated with
      fluoropyrimidine-based regimen presented a shorter overall survival and
      progression-free survival than carriers treated with non-fluoropyrimidine
      regimen. However, non-luminal DPYD c.1627A>G AG/GG carriers treated with TE
      (taxane and anthracycline)-based regimen showed a better prognosis compared with
      carriers treated with non-TE regimen. Our results suggested TE-based chemotherapy
      was a suitable regimen for non-luminal patients with DPYD c.1627A>G AG/GG
      genotype and fluoropyrimidine-based regimen should not be recommended for those
      patients. Our findings provided a novel strategy, which will guide clinicians to
      choose more precise chemotherapy treatment for breast cancer patients.

PMID- 29340112
TI  - Incidence and relative risk of peripheral neuropathy in cancer patients treated
      with eribulin: a meta-analysis.
AB  - Background: Eribulin is a microtubule inhibitor, which is approved for the
      treatment of breast cancer. Peripheral neuropathy has been reported in the
      studies of eribulin, but the incidence and relative risk (RR) of eribulin
      associated peripheral neuropathy varied greatly in cancer patients. The purpose
      of this meta-analysis was to determine the overall incidence and RR of eribulin
      associated peripheral neuropathy in cancer patients. Materials and Methods:
      Pubmed database and Embase and abstracts presented at the American Society of
      Clinical Oncology (ASCO) meetings were systematically reviewed for primary
      studies. Eligible studies included prospective clinical trials and expanded
      access programs of cancer patients treated with eribulin. Statistical analyses
      were performed to calculate the incidences, RRs, and 95% confidence intervals
      (CIs). Results: Altogether, 4,849 patients from 19 clinical trials were selected
      for this meta-analysis. The incidences of all-grade and high-grade peripheral
      neuropathy were 27.5% (95% CI: 23.3-32.4%) and 4.7% (95% CI: 3.6-6.2%),
      respectively. The relative risks of peripheral neuropathy of eribulin compared to
      control were increased for all-grade (RR = 1.89, 95% CI: 1.10-3.25) but not
      statistically significant for high-grade (RR = 2.98, 95% CI: 0.71-12.42).
      Conclusions: The use of eribulin is associated with an increased incidence of
      peripheral neuropathy. The RR is increased for all-grade peripheral neuropathy.

PMID- 29340113
TI  - Prognostic role of platelet to lymphocyte ratio in esophageal cancer: A meta
      analysis.
AB  - Purpose: The prognostic role of inflammation index like platelet to lymphocyte
      ratio (PLR) in esophageal cancer remains controversial. We evaluated the
      prognostic significance of PLR in esophageal cancer patients. Methods: We
      searched databases to identify relevant literatures. Pooled hazard ratios (HRs)
      and 95% confidence intervals (CIs) were calculated. A meta-analysis was performed
      to evaluate the prognostic value of PLR in patients with esophageal cancer.
      Results: A total of 6,699 patients from 16 studies (17 cohorts) were finally
      enrolled in the meta-analysis. The results demonstrate that the elevated PLR
      predicted poorer overall survival (OS) (HR: 1.389, 95% CI: 1.161-1.663) and
      disease-free survival (DFS) (HR: 1.404, 95% CI: 1.169-1.687) and cancer-specific
      survival (CSS) (HR: 1.686, 95% CI: 1.146-2.480) in patients with esophageal
      cancer. Subgroup analysis revealed that the elevated PLR was also associated with
      poor OS in esophageal cancer treated by surgery (HR: 1.492, 95%CI: 1.149-1.938,
      P<0.05) and mixed treatment (HR: 1.222, 95%CI: 1.009-1.479, P<0.05). In addition,
      PLR Cut-off value<=160 (HR: 1.484, 95%CI: 1.088-2.024, P<0.05) and PLR Cut-off
      value>160 (HR: 1.391, 95%CI: 1.161-1.666, P<0.05). Conclusion: This meta-analysis
      result suggested that PLR might be a significant predicative biomarker of poor
      prognosis for esophageal cancer patients.

PMID- 29340114
TI  - Survival benefit evaluation of radiotherapy in esophageal cancer patients aged 80
      and older.
AB  - Purpose: To evaluate the survival benefit of radiotherapy (RT) in esophageal
      cancer (EC) patients aged >= 80. Materials and Methods: Records for all EC
      patients aged >= 65 years were extracted from the Surveillance, Epidemiology, and
      End Results database. Chi-square test compared the characteristic and treatment
      between patients aged >= 80 with those aged 65-79. Focusing on patients aged >=
      80, we employed multivariable logistic regression to identify the association
      between selection of RT and patients' characteristics. Survival curve was
      employed to visualize the survival rate and multivariable Cox proportional hazard
      model was established to quantify the effect of RT on overall survival (OS) and
      cancer special survival (CSS). Results: Patients aged >= 80 were more likely to
      be white male and have localized EC (all P < 0.001). Selection of RT in patients
      aged >= 80 were associated with cancer histology (P < 0.001), grade (P = 0.024)
      and stage (P < 0.001). RT significantly improved the OS (hazard ratio(HR) =
      0.717) and CSS (HR = 0.722) (all P < 0.001). Further stratified analysis found
      the improvement were only significant in the localized (OS HR = 0.662; CSS
      HR=0.652) and regional stage patients (OS HR = 0.571; CSS HR = 0.581) (all P <
      0.001). Conclusions: Our study suggested EC patients aged >= 80 benefit from RT
      only if the cancer is in localized/regional stage.

PMID- 29340115
TI  - Hypermutation and microsatellite instability in gastrointestinal cancers.
AB  - Recent progress in cancer genome analysis using next-generation sequencing has
      revealed a high mutation burden in some tumors. The particularly high rate of
      somatic mutation in these tumors correlates with the generation of neo-antigens
      capable of eliciting an immune response. Identification of hypermutated tumors is
      therefore clinically valuable for selecting patients suitable for immunotherapy
      treatment. There are several known causes of hypermutation in tumors, such as
      ultraviolet light in melanoma, tobacco smoke in lung cancer, and excessive APOBEC
      (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like) activity in
      breast and gastric cancer. In gastrointestinal cancers, one of the leading causes
      of hypermutation is a defect in DNA mismatch repair, which results in
      microsatellite instability (MSI). This review will focus on the frequency,
      characteristics and genomic signature of hypermutated gastrointestinal cancers
      with MSI. Detection of tumor hypermutation in cancer is expected to not only
      predict the clinical benefit of immune checkpoint inhibitor treatment, but also
      to provide better surgical strategies for the patients with hypermutated tumors.
      Thus, in an era of precision medicine, identification of hypermutation and MSI
      will play an important role directing surgical and chemotherapeutic treatment.

PMID- 29340116
TI  - T follicular helper cells: a potential therapeutic target in follicular lymphoma.
AB  - Follicular lymphoma (FL), the most common indolent B-cell non-Hodgkin lymphoma (B
      NHL), is a germinal center (GC)-derived lymphoma. The mechanisms underlying B
      cell differentiation/maturation in GCs could be also involved in their malignant
      transformation. Moreover, the non-malignant cell composition and architecture of
      the tumor microenvironment can influence FL development and outcome. Here, we
      review recent research advances on CD4 helper T cells in FL that highlight the
      pivotal role of T follicular helper (TFH) cells in a complex multicellular system
      where they interact with B cells during GC dynamics. After describing the
      mechanism of FL lymphomagenesis, we discuss the emerging evidence about TFH cell
      enrichment and involvement in FL tumorigenesis and in B-T cell interaction, TFH
      regulation by T follicular regulatory cells (TFR) and its potential effect on FL.
      Then, we provide an overview on the flexible interplay between the different CD4
      T-cell subtypes and how this may be predicted in normal and pathologic contexts,
      according to the cell epigenetic state. Finally, we highlight the importance of
      targeting TFH cells in the clinic, summarize the main outstanding questions about
      TFH and TFR cells in FL, and describe strategies to potentiate FL therapy by
      taking into account TFH cells.

PMID- 29340118
TI  - Apelin/APJ system: A key therapeutic target for liver disease.
AB  - Apelin, a new bioactive peptide, was identified as an endogenous ligand for APJ
      (Angiotensin II receptor-like 1). Apelin and its receptor have an abundant
      distribution in central nervous system and peripheral tissues, including liver.
      Apelin/APJ has diverse physiological and pathological effects, including
      regulation of cardiovascular function, angiogenesis, fluid homeostasis and so on.
      Apelin/APJ system may act as a novel potential therapeutic target for liver
      disease. In this article, we review the role of apelin/APJ system in liver
      fibrosis, hepatitis, hepatic cirrhosis, liver injury and metabolic liver disease.

PMID- 29340117
TI  - The regulation of pre-metastatic niche formation by neutrophils.
AB  - Metastasis is a multistep process requiring tumor cell detachment from the
      primary tumor and migration to target organs through the lymphatic or blood
      circulatory systems. Specific organs are predisposed to metastases in certain
      cancers and the formation of supportive metastatic microenvironment determines
      tumor cell homing. Such an environment is provided by a pre-metastatic niche that
      is formed through the recruitment of bone marrow-derived myeloid cells, however
      the mechanisms of its formation are not fully understood. Recent evidence
      suggests that the primary tumor itself modulates the environment of secondary
      organs prior to tumor cell dissemination. The contribution of neutrophils to the
      formation of the pre-metastatic niche is getting growing attention. Obviously,
      neutrophils can affect the development of metastasis in two contradicting ways,
      by either stimulation or inhibition of this process, depending on the activation
      status. Pro-tumor neutrophils actively support metastasis formation by different
      mechanisms, including the formation of pre-metastatic niche, tumor cell
      attraction, and the direct support of tumor cell proliferation. Moreover,
      suppressive neutrophils, which are the granulocytic arm of MDSC, promote tumor
      progression by dampening anti-tumor T cell immunity. On the other hand, anti
      tumor neutrophils can inhibit metastasis formation by the cytotoxicity towards
      tumor cells in the circulation or at the pre-metastatic site, and even via
      stimulation of T cell proliferation. Apparently, the regulation of the pro- or
      anti-tumor neutrophil properties has significant implications on metastatic
      spread in the host. Here we provide an up to date overview of the different roles
      neutrophils play in regulating the metastatic processes.

PMID- 29340120
TI  - Effect of Short Hydration on Cisplatin-Induced Nephrotoxicity in Cancer Patients:
      A Retrospective Study.
AB  - Background: The aim of this study was to evaluate the protective role of short
      hydration against nephrotoxicity induced by cisplatin (CDDP). Materials and
      Methods: Twenty-two patients (13 men and 9 women) under CDDP therapy were
      enrolled in this retrospective study between 2009 and 2014. The CDDP was given in
      500 ml of isotonic solution, and before and after CDDP administration, the
      patients received 10mEq potassium chloride15% and 1gr magnesium sulfate in 1000
      ml isotonic saline. Renal parameters were evaluated on the first day of each
      cycle of CDDP therapy. Results: Median cumulative CDDP dose was 465 mg/m2. Based
      on renal parameters, the prevalence of CDDP-induced nephrotoxicity (CIN) was
      22.7%, while no hypokalemia and hypomagnesemia were observed. Conclusion: Short
      hydration accompanied with potassium chloride and magnesium sulfate may decrease
      the risk of CIN.

PMID- 29340119
TI  - MEF2 signaling and human diseases.
AB  - The members of myocyte Enhancer Factor 2 (MEF2) protein family was previously
      believed to function in the development of heart and muscle. Recent reports
      indicate that they are also closely associated with development and progression
      of many human diseases. Although their role in cancer biology is well
      established, the molecular mechanisms underlying their action is yet largely
      unknown. MEF2 family is closely associated with various signaling pathways,
      including Ca2+ signaling, MAP kinase signaling, Wnt signaling, PI3K/Akt
      signaling, etc. microRNAs also contribute to regulate the activities of MEF2. In
      this review, we summarize the known molecular mechanism by which MEF2 family
      contribute to human diseases.

PMID- 29340121
TI  - Complications of Transfusion-Dependent beta-Thalassemia Patients in Sistan and
      Baluchistan, South-East of Iran.
AB  - Background: Thalassemia syndromes are among prevalent hereditary disorders
      imposing high expenses on health-care system worldwide and in Iran. Organ failure
      represents a life-threatening challenge in transfusion- dependent beta
      thalassemia (TDT) patients. The purpose of the present study was to determine the
      frequency of organ dysfunctions among TDT patients in Sistan and Baluchistan
      province in South-East of Iran. Materials and Methods: Laboratory and clinical
      data were extracted from medical records as well as by interviews. Standard
      criteria were applied to recognize cardiac, gonadal, endocrine and renal
      dysfunctions. The collected data were analyzed using the SPSS statistics software
      (Ver.19). Results: A total of 613 TDT patients (54.3% males and 45.7% females)
      were included in this study. The mean age of patients was 13.3 +/-7.7 years old.
      Cardiac events comprised the most encountered complications (76.4%), following by
      hypogonadism (46.8%), parathyroid dysfunction (22%), thyroid abnormalities
      (8.3%), diabetes (7.8%) and renal disease (1.8%). Hypogonadism comprised the most
      identified complication in patient <15 years old, while the cardiac complications
      were the most frequent sequela in patients >15 years old (P<0.01). Conclusion: As
      cardiac events are significantly more common among TDT patients, close monitoring
      of the heart function is recommended for identifying patients with cardiac
      problems.

PMID- 29340122
TI  - A Cross-Sectional Study of Glycemic Status and Zinc Level in Patients with Beta
      Thalassemia Major.
AB  - Background: Endocrinopathies and diabetes mellitus are prevalent in patients with
      beta-thalassemia major Recently some studies demonstrate a link between low
      levels of serum zinc level and higher prevalence of diabetes. The aim of this
      study was to evaluate the glucose tolerance in patients suffered from beta
      thalassemia major and determine the association of Homeostasis Model Assessment
      (HOMA) parameters with zinc status among these patients. Materials andMethods: In
      this cross sectional study, clinical data of patients who were suffered from
      thalassemia major, aged>=10 years were collected. Serum ferritin concentration,
      fasting blood sugar, fasting blood insulin and serum zinc level were assessed
      after overnight fasting. Moreover, oral glucose tolerance test was performed.
      Homeostasis Model Assessment (HOMA-2) was used for calculating beta-cell
      function, insulin resistance and sensitivity for normoglycemic and pre-diabetic
      subjects. Results: of the 163 patients diagnosed with beta-thalassemia major,
      10%, 53% and 37% were diabetic, pre-diabetic and normal, respectively. Mean serum
      zinc concentration was equal to 18.90+/-10.93ug/dl, and it was not significantly
      different across diabetic, pre-diabetic and normal groups. Pre-diabetic patients
      had significantly lower beta-cell function compared to normal subjects
      (P=0.0001). An inverse relation was documented between beta-cell function on one
      hand and total units of blood transfusion and ferritin level on the other hand
      (r=-0.29, P=0.004 and r=-0.27, P=0.03, respectively). The analysis adjusted for
      multiple possible confounders showed that there is no significant association
      between HOMA parameters and serum zinc level. Conclusion: Impaired glucose
      metabolism and low serum zinc level were quite common among our study
      participants. The findings of the study also signifies the substantial role of
      follow-up in early detection and appropriate treatment.

PMID- 29340123
TI  - Multiple Extramedullary Plasmacytoma in a Setting of Complete Bone Marrow
      Remission: Food for Thought.
AB  - Extramedullary plasmacytoma as a mode of relapse in multiple myeloma (MM) is
      unusual. Current recommendations do not incorporate the routine use of 18
      fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET/CT)
      imaging prior to haematopoietic stem cell transplant (HSCT) in MM. We report a
      case of relapsed MM with complete remission as per IMWG criteria. In the interim
      period, before the HSCT, the patient had localizing neurological signs and
      symptoms attributed to multiple extramedullary plasmacytomas. The uniqueness of
      this case is that this patient after complete marrow remission with no obvious
      external masses had unexpected, symptomatic multiple extramedullary
      plasmacytomas. This case illustrates the need for integration of FDG PET/CT
      imaging into routine pre-HSCT investigations in relapsed MM to prevent missing
      any asymptomatic extramedullary plasmacytomas.

PMID- 29340124
TI  - The Use of Filgrastim in Patients with Hodgkin Lymphoma Receiving ABVD.
AB  - Background: There is conflicting data about the increased risk of pulmonary
      toxicity when granulocyte-stimulating factor (G-CSF) is given in combination with
      bleomycin. No clear consensus for management of patients with Hodgkin lymphoma
      (HL) who require G-CSF support exists. Our objective was to evaluate whether
      there is an increase in pulmonary toxicity in patients who receive bleomycin and
      G-CSF during treatment for HL. Materials and Methods: We conducted a single
      center retrospective analysis of patients with Hodgkin Lymphoma from January 2003
      until July 2015. All patients who received at least 1 dose of bleomycin and
      followed at our institution were included. Patients were evaluated for pulmonary
      toxicity starting from the day of first dose of bleomycin until 1 year after
      initiation of bleomycin. Data on pre-identified risk factors for pulmonary
      toxicity were also collected. Results: Fifty-four patients met inclusion
      criteria. Twenty-one patients received bleomycin alone, and 33 patients received
      bleomycin and G-CSF. There was no statistically significant (p = 0.50) difference
      in the development of pulmonary toxicity between the two groups. Crude hazard
      ratio for development of pulmonary toxicity in the bleomycin and G-CSF cohort was
      1.58 (95% confidence interval, CI: 0.41-6.12). On multivariate analysis, the
      hazard ratio for development of pulmonary toxicity was 1.71 (95% CI: 0.43-6.81).
      Conclusion: This study does not find evidence that the combination of bleomycin
      and G-CSF increases the risk for bleomycin- induced pulmonary toxicity. We
      recommend G-CSF use in HL patients receiving bleomycin when needed to maintain
      dose intensity.

PMID- 29340125
TI  - Rare Presentation of Refractory Thrombotic Thrombocytopenic Purpura: Jejunal
      Stricture.
AB  - Thrombotic thrombocytopenic purpura is a rare thrombotic disease characterized by
      episodes of thrombocytopenia and microangiopathic hemolytic anemia due to
      disseminated microvascular thrombosis. Thrombotic thrombocytopenic purpura was
      first described in 1924 by Moschowitz as a disease presenting with a pentad of
      signs and symptoms (anemia, thrombocytopenia, fever, hemiparesis and hematuria).
      Previous studies have described atypical manifestations of thrombotic
      thrombocytopenic purpura such as hemolysis, anemia and thrombosis.

PMID- 29340126
TI  - Hepatosplenic Gamma Delta T-Cell Lymphoma (HSGDTCL): Two Rare Case Reports from
      Western India.
AB  - Peripheral T cell lymphomas are a heterogeneous group of post-thymic, mature
      lymphoid malignancies, accounting for approximately 10-15% of all non-Hodgkin's
      lymphomas. Hepatosplenic T-cell lymphoma (HSGDTCL) is a rare entity, which is
      characterized by primary extra nodal disease with typical sinusoidal or sinusal
      infiltration of the liver and the spleen, respectively by expression of the T
      cell receptor gammadelta chain, and by a number of other frequent
      clinicopathologic features, including aggressive course of disease. Secondary
      involvement of liver by hematopoietic malignancies is much more common as
      compared to primary liver involvement. Primary involvement of liver by non-
      Hodgkin's lymphoma (NHL) is documented and mostly DLBCL (diffuse large B cell
      lymphoma) type. But, T cell lymphoma primarily arising from liver is very rare.
      It occurred commonly in immunocompromised patients and prognosis is very poor.
      Here, we present two case reports of Hepatosplenic gamma-delta T-cell lymphoma
      (HSGDTCL) and both are immunocompetent patients. Liver biopsy from the mass and
      subsequent IHC (immunohistochemistry) were performed for the purpose of
      diagnosis, which were positive for LCA (leukocyte common antigen), CD2 and
      negative for CD5, CD20 and CD79a. First patient was a 63-year-old female with
      hepatitis C virus seropositivity presented with liver mass simulating
      hepatocellular carcinoma. Second patient was a 60-year- old male, chronic
      alcoholic patient, presented with liver mass and lytic bony lesion in pelvis.
      Both patients were managed with conventional CHOP (cyclophosphamide,
      hydroxydaunorubicin, vincristine, and prednisolone) and showed complete response
      after 4 cycles of chemotherapy. After completion of 6 cycles of chemotherapy,
      both patients remained under 6-month surveillance period for any recurrence of
      the disease.

PMID- 29340127
TI  - Restarting Thalidomide-Dexamethasone Regimen in a Post-Abortive Female with
      Multiple Myeloma: Effective Clinical Response Possible.
AB  - Nowadays, the prevalence of Multiple Myeloma (MM) seems to have been increasing
      among young females. Here, we report that thalidomide is contraindicated in
      pregnant women diagnosed with MM and those desirous of subsequent pregnancy. In
      this case report, we compared the clinical response of Thalidomide-Dexamethasone
      therapy in a post-abortive woman with persistently elevated beta-hCG levels due
      to retained products of conception, undergoing hysterectomy later. This case
      report underlines the clinical significance of age, the effect of Thalidomide
      Dexamethasone therapy even after initial discontinuation and the response to high
      beta-hCG levels.

PMID- 29340128
TI  - Hematological Reference Intervals for Healthy Iranian Blood Donors.
AB  - Background: Development of locally-derived hematological reference intervals is
      necessary for improving the quality of health care and clinical trials. However
      hematological reference intervals are affected by several variables including
      age, gender and environmental factors. Therefore this study was conducted to
      determine the gender and age-specific hematological reference intervals of
      healthy Iranian blood donors. Materials and Methods: Selected hematological
      indices of 394 healthy blood donor volunteers, donating blood at Tehran Blood
      Transfusion Center were analyzed. Hematological reference intervals, stratified
      by age and gender were compared. The results of current study were also compared
      with those of US population. Results: There were significant gender-related
      differences for mean values of hematological indices, with males having higher
      mean values of RBC, HCG, HCT and MCV than females. While the mean of PLT and MCH
      were higher in women. Age-related differences for mean values of RBC and MCH were
      also significant. The comparison of reference intervals, stratified by both
      gender and age showed that RBC, HGB and HCT values were higher in males than
      females in all age groups. But MCH values of females in all age groups and WBC
      and PLT counts in females older than 30 years were higher compared to the males
      in the same age group. The results of this study showed some similarity with US
      population, with narrower intervals. Conclusion: This study suggests that gender
      and age-specific, locally derived hematological reference intervals should be
      referred to, before interpretation of any laboratory test result.

PMID- 29340129
TI  - Protective Isolation for Patients with Haematological Malignancies: A Pilot Study
      Investigating Patients' Distress and Use of Time.
AB  - Background: Patients with haematological malignancies are often hospitalized in
      protective isolation until full neutrophil recovery in order to prevent
      infections. This descriptive pilot study evaluate the level of isolation-related
      distress and the use of free time in a sample of Italian onco-haematological
      patients who were hospitalized in protective isolation. Materials and Methods:
      Participants were 18 patients hospitalized in hematologic ward to receive
      induction therapy (n=12) or autologous stem cell transplant (n=6). They completed
      a self-report questionnaire before discharge. Results: Participants reported a
      moderate level of isolation-related distress, anxiety, and boredom: the more the
      anxiety and the boredom, the more the distress (r=.77; P<.001), (r=.79; P<.001),
      respectively. The activities performed during isolation were: watching TV
      (72.2%), reading (55.6%), thinking (33.3%), surfing in Internet or using PC
      (33.3%), and playing games or making cross-words (16.7%). Participants who
      reported pessimistic thinking had higher isolation-related distress (P=.004) as
      well as anxiety (P<.001) and boredom (P=.001). Conclusion: Haematology Units
      should support isolated patients in spending their time in recreational
      activities, allowing more contacts with immediate relatives and friends,
      providing free TV and Wi-Fi connection inside the room. In addition, patients
      should have to keep themselves physically active. Isolation-related distress
      could also be reduced by providing psychological support.

PMID- 29340130
TI  - Mechanism Action of Platelets and Crucial Blood Coagulation Pathways in
      Hemostasis.
AB  - Blood is considered to be precious because it is the basic necessity for health;
      our body needs a steady provision of oxygen, supplied via blood, to reach
      billions of tissues and cells. Hematopoiesis is the process that generates blood
      cells of all lineages. However, platelets are the smallest blood component
      produced from the very large bone marrow cells called megakaryocytes and they
      play a fundamental role in thrombosis and hemostasis. Platelets contribute their
      hemostatic capacity via adhesion, activation and aggregation, which are triggered
      upon tissue injury, and these actions stimulate the coagulation factors and other
      mediators to achieve hemostasis. In addition, these coordinated series of events
      are the vital biological processes for wound healing phases. The aim of this
      review is to summarize and highlight the important pathways involved in achieving
      hemostasis that are ruled by platelets. In addition, this review also describes
      the mechanism action of platelets, including adhesion, activation, aggregation,
      and coagulation, as well as the factors that aid in hemostasis and wound healing.

PMID- 29340131
TI  - Acute Myeloid Leukemia-Genetic Alterations and Their Clinical Prognosis.
AB  - Acute myeloid leukemia (AML) is a group of hematological diseases, phenotypic and
      genetically heterogeneous, characterized by abnormal accumulation of blast cells
      in the bone marrows and peripheral blood. Its incidence rate is approximately 1.5
      per 100,000 in infants younger than 1 year of age and 25 per 100,000 persons in
      octogenarians. Traditionally, cytogenetic markers are used to stratify patients
      in three risk categories: favorable, intermediate and unfavorable. However, the
      forecast stratification and the treatment decision for patients with normal
      karyotype shows difficulties due to the high clinical heterogeneity. The
      identification of several genetic mutations additional to classical molecular
      markers has been useful in identifying new entities. Nowadays, many different
      mutations and epigenetic aberrations have been implicated in the diagnostic,
      prognostic and treatment of AML. This review is focused on describing the most
      important molecular markers with implications for clinical practice.

PMID- 29340132
TI  - Effect of epilepsy on autism symptoms in Angelman syndrome.
AB  - Background: Autism spectrum disorder and epilepsy often co-occur; however, the
      extent to which the association between autism symptoms and epilepsy is due to
      shared aetiology or to the direct effects of seizures is a topic of ongoing
      debate. Angelman syndrome (AS) is presented as a suitable disease model to
      explore this association. Methods: Data from medical records and questionnaires
      were used to examine the association between age of epilepsy onset, autism
      symptoms, genetic aberration and communication level. Forty-eight participants
      had genetically verified AS (median age 14.5 years; range 1-57 years). A measure
      of autism symptoms (the Social Communication Questionnaire; SCQ) was completed
      for 38 individuals aged >= 4 years. Genetic cause was subgrouped into deletion
      and other genetic aberrations of the 15q11-q13 area. The number of signs used to
      communicate (< 20 sign and >= 20 signs) was used as a measure of nonverbal
      communication. Results: Mean age of epilepsy onset was 3.0 years (range 3 months
      7.8 years). Mean SCQ score for individuals without epilepsy was 13.6 (SD = 6.7)
      and with epilepsy 17.0 (SD = 5.6; p = 0.17); 58% used fewer than 20 signs to
      communicate. There were no age differences between groups according to presence
      of epilepsy, level of nonverbal communication or type of genetic aberration. SCQ
      scores were higher in individuals with the deletion than in those with other
      genetic aberrations (18.7 vs 10.8 p = 0.008) and higher in the group who used <
      20 signs to communicate (19.4 vs 14.1 p = 0.007). Age of epilepsy onset was
      correlated with SCQ (r = - 0.61, p < 0.001). Multiple regression showed that age
      of seizure onset was significantly related to SCQ score (beta = - 0.90; p =
      0.006), even when the type of genetic abnormality was controlled (R2 = 0.53; F =
      10.7; p = 0.001). Conclusions: The study provides support for the notion that
      seizures themselves contribute more to autism symptoms than expected from the
      underlying genetic pathology alone. The study demonstrates how a rare genetic
      syndrome such as Angelman syndrome may be used to study the relation between
      epilepsy and autism symptomatology.

PMID- 29340133
TI  - A regional assessment of white-tailed deer effects on plant invasion.
AB  - Herbivores can profoundly influence plant species assembly, including plant
      invasion, and resulting community composition. Population increases of native
      herbivores, e.g. white-tailed deer (Odocoileus virginianus), combined with
      burgeoning plant invasions raise concerns for native plant diversity and forest
      regeneration. While individual researchers typically test for the impact of deer
      on plant invasion at a few sites, the overarching influence of deer on plant
      invasion across regional scales is unclear. We tested the effects of deer on the
      abundance and diversity of introduced and native herbaceous and woody plants
      across 23 white-tailed deer research sites distributed across the east-central
      and north-eastern USA and representing a wide range of deer densities and
      invasive plant abundance and identity. Deer access/exclusion or deer population
      density did not affect introduced plant richness or community-level abundance.
      Native and total plant species richness, abundance (cover and stem density) and
      Shannon diversity were lower in deer-access vs. deer-exclusion plots. Among deer
      access plots, native species richness, native and total cover, and Shannon
      diversity (cover) declined as deer density increased. Deer access increased the
      proportion of introduced species cover (but not of species richness or stem
      density). As deer density increased, the proportion of introduced species
      richness, cover and stem density all increased. Because absolute abundance of
      introduced plants was unaffected by deer, the increase in proportion of
      introduced plant abundance is likely an indirect effect of deer reducing native
      cover. Indicator species analysis revealed that deer access favoured three
      introduced plant species, including Alliaria petiolata and Microstegium vimineum,
      as well as four native plant species. In contrast, deer exclusion favoured three
      introduced plant species, including Lonicera japonica and Rosa multiflora, and 15
      native plant species. Overall, native deer reduced community diversity, lowering
      native plant richness and abundance, and benefited certain invasive plants,
      suggesting pervasive impacts of this keystone herbivore on plant community
      composition and ecosystem services in native forests across broad swathes of the
      eastern USA.

PMID- 29340134
TI  - Does mycorrhizal status alter herbivore-induced changes in whole-plant resource
      partitioning?
AB  - Both mycorrhizae and herbivore damage cause rapid changes in source-sink dynamics
      within a plant. Mycorrhizae create long-term sinks for carbon within the roots
      while damage by leaf-chewing herbivores causes temporary whole-plant shifts in
      carbon and nitrogen allocation. Thus, induced responses to herbivory might depend
      on the presence or absence of mycorrhizae. We examined the effects of mycorrhizal
      presence on induced resource partitioning in tomato (Solanum lycopersicon) in
      response to cues from a specialist herbivore Manduca sexta. Differences in plant
      size, growth and in the concentrations of carbon-based (soluble sugars and
      starch) and nitrogen-based (protein and total nitrogen) resources in three tissue
      types (apex, stem and roots) were quantified. Both mycorrhizae and simulated
      herbivory altered the concentrations of carbon- and nitrogen-based resources.
      Mycorrhizae promoted plant growth, altered sugar and starch levels. Simulated
      herbivory resulted in lower concentrations of most resources (sugar, starch and
      protein) in the rapidly growing apex tissue, while causing an increase in stem
      protein. There was only one interactive effect; the effects of simulated
      herbivory were much stronger on the sugar concentration in the apex of non
      mycorrhizal plants. This clearly demonstrates that both mycorrhizal colonization
      and herbivore cues cause shifts in carbon- and nitrogen-based resources and
      further shows there is little interference by mycorrhizae on the direction and
      magnitude of plant responses to herbivory. Overall, our results suggest that
      herbivore cues, regardless of mycorrhizal status, reduce allocation to the
      growing apex while inducing protein storage in the stem, a possible mechanism
      that could increase the tolerance of plants to damage.

PMID- 29333233
TI  - On the primacy and irreducible nature of first-person versus third-person
      information.
AB  - In this essay, we will support the claim that at the current level of scientific
      advancement a) some first-person accounts cannot be reduced to their third-person
      neural and psychophysiological correlates and b) that these first-person accounts
      are the only information to reckon when it is necessary to analyse qualia
      contents. Consequently, for many phenomena, first-person accounts are the only
      reliable source of information available and the knowledge of their neural and
      psychophysical correlates don't offer any additional information about them.

PMID- 29333234
TI  - Case Report: Laparoscopic hepatectomy in an elderly patient with major
      comorbidities.
AB  - Surgeons have been hesitant to proceed to hepatectomy in elderly patients, due to
      the higher rate of comorbidities and the reduced reserves. An 81-year-old male
      with hepatocellular carcinoma in the segment VI of the liver and several major
      cardiovascular, pulmonary and metabolic comorbid illnesses was referred to our
      department for treatment. He underwent transarterial chemoembolization of the
      liver tumor and afterwards he underwent laparoscopic resection of the hepatic
      segment VI, with an uneventful postoperative course. This case indicates that
      laparoscopic liver resections could be applied even to elderly patients with
      major comorbidities after optimization of their medical status.

PMID- 29333233
TI  - On the primacy and irreducible nature of first-person versus third-person
      information.
AB  - In this essay, we will support the claim that at the current level of scientific
      advancement a) some first-person accounts cannot be reduced to their third-person
      neural and psychophysiological correlates and b) that these first-person accounts
      are the only information to reckon when it is necessary to analyse qualia
      contents. Consequently, for many phenomena, first-person accounts are the only
      reliable source of information available and the knowledge of their neural and
      psychophysical correlates don't offer any additional information about them.

PMID- 29333235
TI  - Case Report: Synchronous primary malignancy including the breast and endometrium.
AB  - Breast and endometrial cancer are the most common types of female cancers, but
      the incidence of both of these malignancies in a single patient is a rare event.
      Multiple primary malignancy has been increasingly reported over the past decade,
      and double primary cancer is considered as the most common type.  In this study,
      we present a 53-year-old woman with synchronous primary malignancy of breast and
      endometrium. This patient had a history of breast and endometrial cancer in her
      family. Mammography and chest CT of the patient revealed a mass in the right
      breast and left supraclavicular region. However, the patient did not want to
      initiate treatment. Subsequently, the patient returned with a chief complaint of
      persistent abnormal vaginal bleeding. Abdominopelvic CT scan of the patient
      revealed a huge soft tissue mass in the pelvic cavity. She underwent
      hysterectomy, and pathology revealed endometrioid carcinoma, which had invaded
      the full thickness of uterine wall. Since this type of malignancy is rare and
      several risk factors are associated with it, it is worth being considered by
      clinicians when making decisions about screening or strategy for prevention.

PMID- 29333237
TI  - Draft genome of tule elk Cervus canadensis nannodes.
AB  - This paper presents the first draft genome of the tule elk ( Cervus elaphus
      nannodes), a subspecies native to California that underwent an extreme genetic
      bottleneck in the late 1800s.  The genome was generated from Illumina HiSeq 3000
      whole genome sequencing of four individuals, resulting in the assembly of 2.395
      billion base pairs (Gbp) over 602,862 contigs over 500 bp and N50 = 6,885 bp.
      This genome provides a resource to facilitate future genomic research on elk and
      other cervids.

PMID- 29333236
TI  - In silico analysis of natural compounds targeting structural and nonstructural
      proteins of chikungunya virus.
AB  - Background: Chikungunya fever presents as a high-grade fever during its acute
      febrile phase and can be prolonged for months as chronic arthritis in affected
      individuals. Currently, there are no effective drugs or vaccines against this
      virus. The present study was undertaken to evaluate protein-ligand interactions
      of all chikungunya virus (CHIKV) proteins with natural compounds from a MolBase
      library in order to identify potential inhibitors of CHIKV. Methods: Virtual
      screening of the natural compound library against four non-structural and five
      structural proteins of CHIKV was performed. Homology models of the viral proteins
      with unknown structures were created and energy minimized by molecular dynamic
      simulations. Molecular docking was performed to identify the potential inhibitors
      for CHIKV. The absorption, distribution, metabolism and excretion (ADME) toxicity
      parameters for the potential inhibitors were predicted for further prioritization
      of the compounds. Results: Our analysis predicted three compounds, Catechin-5-O
      gallate, Rosmarinic acid and Arjungenin, to interact with CHIKV proteins; two
      (Catechin-5-O-gallate and Rosmarinic acid) with capsid protein, and one
      (Arjungenin) with the E3. Conclusion: The compounds identified show promise as
      potential antivirals, but further in vitro studies are required to test their
      efficacy against CHIKV.

PMID- 29333239
TI  - The peer review process for awarding funds to international science research
      consortia: a qualitative developmental evaluation.
AB  - Background: Evaluating applications for multi-national, multi-disciplinary, dual
      purpose research consortia is highly complex. There has been little research on
      the peer review process for evaluating grant applications and almost none on how
      applications for multi-national consortia are reviewed. Overseas development
      investments are increasingly being channelled into international science
      consortia to generate high-quality research while simultaneously strengthening
      multi-disciplinary research capacity. We need a better understanding of how such
      decisions are made and their effectiveness. Methods: An award-making institution
      planned to fund 10 UK-Africa research consortia. Over two annual rounds, 34 out
      of 78 eligible applications were shortlisted and reviewed by at least five
      external reviewers before final selections were made by a face-to-face panel. We
      used an innovative approach involving structured, overt observations of award
      making panel meetings and semi-structured interviews with panel members to
      explore how assessment criteria concerning research quality and capacity
      strengthening were applied during the peer review process. Data were coded and
      analysed using pre-designed matrices which incorporated categories relating to
      the assessment criteria. Results: In general the process was rigorous and well
      managed. However, lack of clarity about differential weighting of criteria and
      variations in the panel's understanding of research capacity strengthening
      resulted in some inconsistencies in use of the assessment criteria. Using the
      same panel for both rounds had advantages, in that during the second round
      consensus was achieved more quickly and the panel had increased focus on
      development aspects. Conclusion: Grant assessment panels for such complex
      research applications need to have topic- and context-specific expertise. They
      must also understand research capacity issues and have a flexible but equitable
      and transparent approach. This study has developed and tested an approach for
      evaluating the operation of such panels and has generated lessons that can
      promote coherence and transparency among grant-makers and ultimately make the
      award-making process more effective.

PMID- 29333240
TI  - The use of dexmedetomidine and intravenous acetaminophen for the prevention of
      postoperative delirium in cardiac surgery patients over 60 years of age: a pilot
      study.
AB  - Background: Delirium is associated with many negative health outcomes.
      Postoperative sedation and opioid administration may contribute to delirium. We
      hypothesize that the use of dexmedetomidine and Intravenous acetaminophen (IVA)
      may lead to reduced opioid consumption and decreased incidence of postoperative
      delirium. This pilot study aims to assess feasibility of using dexmedetomidine
      and IVA in cardiac surgical patients, and estimate the effect size for incidence
      and duration of delirium. Methods: A total of 12 adult patients >60 years of age
      undergoing cardiac surgery were recruited and randomized into 4 groups: Propofol
      only (P), Propofol with IVA (P+A), Dexmedetomidine only (D), Dexmedetomidine with
      IVA (D+A). Preoperative baseline cognition and postoperative delirium was
      assessed daily until discharge. The feasibility was assessed by the number of
      patients who completed the study. Results: All patients completed the study
      successfully. The total incidence of delirium in the study population was 42%
      (5/12):  67% (2/3) in the group P, and 67% (2/3) in the group D, 33% (1/3) in 
      D+A group and 0%(0/3)  P+A group. The incidence of delirium was 17% (1/6) in the
      group receiving IVA compared to 67% (4/6) that did not receive IVA. The mean
      range of duration of delirium was 0-1 days. One patient expired after surgery,
      unrelated to the study protocol. One patient in the D group experienced
      hypotension (systolic blood pressure <90 mm of Hg.) Conclusions: The feasibility
      of performing a  project is ascertained by the study. Patients receiving IVA had
      lower incidence of delirium compared to patients not receiving IVA which suggests
      that IVA may have a role in reducing the incidence of delirium. A prospective
      randomized, placebo-controlled trial will be the next step in investigating the
      role of dexmedetomidine and IVA in reducing the incidence of delirium.

PMID- 29333241
TI  - Developing data interoperability using standards: A wheat community use case.
AB  - In this article, we present a joint effort of the wheat research community, along
      with data and ontology experts, to develop wheat data interoperability
      guidelines. Interoperability is the ability of two or more systems and devices to
      cooperate and exchange data, and interpret that shared information.
      Interoperability is a growing concern to the wheat scientific community, and
      agriculture in general, as the need to interpret the deluge of data obtained
      through high-throughput technologies grows. Agreeing on common data formats,
      metadata, and vocabulary standards is an important step to obtain the required
      data interoperability level in order to add value by encouraging data sharing,
      and subsequently facilitate the extraction of new information from existing and
      new datasets. During a period of more than 18 months, the RDA Wheat Data
      Interoperability Working Group (WDI-WG) surveyed the wheat research community
      about the use of data standards, then discussed and selected a set of
      recommendations based on consensual criteria. The recommendations promote
      standards for data types identified by the wheat research community as the most
      important for the coming years: nucleotide sequence variants, genome annotations,
      phenotypes, germplasm data, gene expression experiments, and physical maps. For
      each of these data types, the guidelines recommend best practices in terms of use
      of data formats, metadata standards and ontologies. In addition to the best
      practices, the guidelines provide examples of tools and implementations that are
      likely to facilitate the adoption of the recommendations. To maximize the
      adoption of the recommendations, the WDI-WG used a community-driven approach that
      involved the wheat research community from the start, took into account their
      needs and practices, and provided them with a framework to keep the
      recommendations up to date. We also report this approach's potential to be
      generalizable to other (agricultural) domains.

PMID- 29333243
TI  - Unexpected results in Chernozem soil respiration while measuring the effect of a
      bio-fertilizer on soil microbial activity.
AB  - The number of studies investigating the effect of bio-fertilizers is increasing
      because of their importance in sustainable agriculture and environmental quality.
      In our experiments, we measured the effect of different fertilizers on soil
      respiration. In the present study, we were looking for the cause of unexpected
      changes in CO2 values while examining Chernozem soil samples. We concluded that
      CO2 oxidizing microbes or methanotrophs may be present in the soil that
      periodically consume CO2 . This is unusual for a sample taken from the upper
      layer of well-ventilated Chernozem soil with optimal moisture content.

PMID- 29333242
TI  - Predictive value of early postoperative IOP and bleb morphology in Mitomycin-C
      augmented trabeculectomy.
AB  - Background: To determine the predictive value of postoperative bleb morphological
      features and intraocular pressure (IOP) on the success rate of trabeculectomy.
      Methods: In this prospective interventional case series, we analyzed for one year
      80 consecutive primary open angle glaucoma patients who underwent mitomycin
      augmented trabeculectomy. Bleb morphology was scored using the Indiana bleb
      appearance grading scale (IBAGS). Success was defined as IOP <=15 mmHg at 12
      months. We applied a multivariable regression analysis and determined the area
      under the receiver operating characteristic curve (AUC). Results: The mean age of
      participants was 62+/-12.3 years in the success and 63.2+/-16.3 years in the
      failure group (P= 0.430) with equal gender distribution (P=0.911). IOPs on day 1,
      7 and 30 were similar in both (P= 0.193, 0.639, and 0.238, respectively.) The AUC
      of IOP at day 1, day 7 and 30 for predicting a successful outcome was 0.355,
      0.452, and 0.80, respectively. The AUC for bleb morphology parameters of bleb
      height, extension, and vascularization, on day 14 were 0.368, 0.408, and 0.549,
      respectively. Values for day 30 were 0.428, 0.563, and 0.654. IOP change from day
      1 to day 30 was a good predictor of failure (AUC=0.838, 95% CI: 0.704 to 0.971)
      with a change of more than 3 mmHg predicting failure with a sensitivity of 82.5%
      (95% CI: 68 to 91%) and a specificity of 87.5% (95% CI: 53 to 98%). Conclusions:
      IOP on day 30 had a fair to good accuracy while bleb features failed to predict
      success except bleb vascularity that had a poor to fair accuracy.  An IOP
      increase more than 3 mmHg during the first 30 days was a good predictor of
      failure.

PMID- 29333244
TI  - Infectious pancreatic necrosis virus triggers antiviral immune response in
      rainbow trout red blood cells, despite not being infective.
AB  - Background: Some fish viruses, such as piscine orthoreovirus and infectious
      salmon anemia virus, target red blood cells (RBCs), replicate inside them and
      induce an immune response. However, the roles of RBCs in the context of
      infectious pancreatic necrosis virus (IPNV) infection  have not been studied yet.
      Methods: Ex vivo rainbow trout RBCs were obtained from peripheral blood, Ficoll
      purified and exposed to IPNV in order to analyze infectivity and immune response
      using RT-qPCR, immune fluorescence imaging, flow cytometry and western-blotting
      techniques. Results: IPNV could not infect RBCs; however, IPNV increased the
      expression of the INF1-related genes ifn-1, pkr and mx genes. Moreover,
      conditioned media from IPNV-exposed RBCs conferred protection against IPNV
      infection in CHSE-214 fish cell line. Conclusions: Despite not being infected,
      rainbow trout RBCs could respond to IPNV with increased expression of antiviral
      genes. Fish RBCs could be considered as mediators of the antiviral response and
      therefore targets of new strategies against fish viral infections. Further
      research is ongoing to completely understand the molecular mechanism that
      triggers this antiviral response in rainbow trout RBCs.

PMID- 29333245
TI  - The impact of fresh gas flow on wash-in, wash-out time and gas consumption for
      sevoflurane and desflurane, comparing two anaesthesia machines, a test-lung
      study.
AB  - Low-flow anaesthesia is considered beneficial for the patient and the
      environment, and it is cost reducing due to reduced anaesthetic gas consumption.
      An initial high-flow to saturate the circle system ( wash-in) is desirable from a
      clinical point of view. We measured the wash-in and wash-out times (time to
      saturate and to eliminate the anaesthetic agent, AA), for sevoflurane and
      desflurane, in a test-lung with fixed 3 MAC vaporizer setting at different fresh
      gas flow (FGF) and calculated the consumption of AA. We tried to find an optimal
      flow rate for speed and gas consumption, comparing two anaesthesia machines
      (AMs): Aisys and Flow-i. Time to reach 1 minimal alveolar concentration (MAC)
      (wash-in) decreased (p<0.05) at higher flow rates (1 - 2 - 4) but plateaued at 4
      4.8 l/min. The consumption of AA was at its lowest around 4-4.8 l/min (optimal
      flow) for all but the Aisys /desflurane group. Wash-out times decreased as FGF
      increased, until reaching plateau at FGF of 4-6 l/min. Aisys had generally
      shorter wash-in times at flow rates < 4 l/min as well as lower consumption of AA.
      At higher flow rates there were little difference between the AMs. The "optimal
      FGF" for wash-out, elimination of gas from the test-lung and circle system,
      plateaued with no increase in speed beyond 6 l/min. A fresh gas flow of 4 l/min.
      seems "optimal" taking speed to reach a 1 MAC ET and gas consumption into account
      during wash-in with a fixed 3 MAC vaporizer setting, and increasing fresh gas
      flow beyond 6 l/min does not seem to confirm major benefit during wash-out.

PMID- 29340148
TI  - Reducing unnecessary culturing: a systems approach to evaluating urine culture
      ordering and collection practices among nurses in two acute care settings.
AB  - Background: Inappropriate ordering and acquisition of urine cultures leads to
      unnecessary treatment of asymptomatic bacteriuria (ASB). Treatment of ASB
      contributes to antimicrobial resistance particularly among hospital-acquired
      organisms. Our objective was to investigate urine culture ordering and collection
      practices among nurses to identify key system-level and human factor barriers and
      facilitators that affect optimal ordering and collection practices. Methods: We
      conducted two focus groups, one with ED nurses and the other with ICU nurses.
      Questions were developed using the Systems Engineering Initiative for Patient
      Safety (SEIPS) framework. We used iterative categorization (directed content
      analysis followed by summative content analysis) to code and analyze the data
      both deductively (using SEIPS domains) and inductively (emerging themes).
      Results: Factors affecting optimal urine ordering and collection included
      barriers at the person, process, and task levels. For ED nurses, barriers
      included patient factors, physician communication, reflex culture protocols, the
      electronic health record, urinary symptoms, and ED throughput. For ICU nurses,
      barriers included physician notification of urinalysis results, personal
      protective equipment, collection technique, patient body habitus, and Foley
      catheter issues. Conclusions: We identified multiple potential process barriers
      to nurse adherence with evidence-based recommendations for ordering and
      collecting urine cultures in the ICU and ED. A systems approach to identifying
      barriers and facilitators can be useful to design interventions for improving
      urine ordering and collection practices.

PMID- 29340149
TI  - Acute kidney injury due to multiple Hymenoptera stings-a clinicopathological
      study.
AB  - Background: Acute kidney injury (AKI) after multiple Hymenoptera stings is well
      known but still a rare phenomenon. Methods: We conducted a retrospective study of
      the clinicopathological spectrum of AKI due to multiple Hymenoptera stings over
      13 years (July 2003-June 2016). Results: A total of 35 patients were diagnosed
      with AKI due to multiple Hymenoptera stings. The mean age of the patients was
      44.7 +/- 17.4 years and the majority (60%) were men. Haematological and
      biochemical laboratory abnormalities included anaemia (97.1%), leucocytosis
      (54.3%), hyperkalaemia (68.6%), severe metabolic acidosis (51.4%), hepatic
      dysfunction (74.3%), haemolysis (91.4%) and rhabdomyolysis (62.9%). The main
      complications included acute respiratory distress syndrome (ARDS) and
      encephalopathy in four (11.4%) patients each; gastrointestinal bleeding,
      hypertension and panniculitis in two (5.7%) patients each and one (2.9%) patient
      each developed intra-abdominal bleeding, stroke and polyserositis. Twenty-nine
      (83%) patients required dialysis. Ten (29%) patients died. A higher white blood
      cell count (P = 0.05) and the complications of ARDS (P = 0.004) and
      encephalopathy (P = 0.004) were associated with mortality. The kidney functions
      normalized at 5.5 +/- 2.6 weeks in patients who survived. Kidney biopsy was done
      in 13 patients. The predominant lesion was acute tubular necrosis (ATN) with or
      without pigmented granular cast in 10 (77%) patients. In four (30.8%) patients,
      the kidney biopsy showed severe ATN and in the other six (46.2%), the kidney
      biopsy showed features of ATN associated with mild to moderate acute interstitial
      nephritis (AIN). In three (23%) patients the histopathological examination
      revealed only moderate AIN and these patients were treated with a short course of
      steroids. Conclusions: AKI due to multiple Hymenoptera stings is severe and is
      associated with high mortality. On renal histology, ATN and AIN are common.

PMID- 29340150
TI  - Xylose: absorption, fermentation, and post-absorptive metabolism in the pig.
AB  - Xylose, as beta-1,4-linked xylan, makes up much of the hemicellulose in cell
      walls of cereal carbohydrates fed to pigs. As inclusion of fibrous ingredients in
      swine diets continues to increase, supplementation of carbohydrases, such as
      xylanase, is of interest. However, much progress is warranted to achieve
      consistent enzyme efficacy, including an improved understanding of the
      utilization and energetic contribution of xylanase hydrolysis product (i.e.
      xylooligosaccharides or monomeric xylose). This review examines reports on xylose
      absorption and metabolism in the pig and identifies gaps in this knowledge that
      are essential to understanding the value of carbohydrase hydrolysis products in
      the nutrition of the pig. Xylose research in pigs was first reported in 1954,
      with only sporadic contributions since. Therefore, this review also discusses
      relevant xylose research in other monogastric species, including humans. In both
      pigs and poultry, increasing purified D-xylose inclusion generally results in
      linear decreases in performance, efficiency, and diet digestibility. However,
      supplementation levels studied thus far have ranged from 5% to 40%, while
      theoretical xylose release due to xylanase supplementation would be less than 4%.
      More than 95% of ingested D-xylose disappears before the terminal ileum but
      mechanisms of absorption have yet to be fully elucidated. Some data support the
      hypothesis that mechanisms exist to handle low xylose concentrations but become
      overwhelmed as luminal concentrations increase. Very little is known about xylose
      metabolic utilization in vertebrates but it is well recognized that a large
      proportion of dietary xylose appears in the urine and significantly decreases the
      metabolizable energy available from the diet. Nevertheless, evidence of labeled D
      xylose-1-14C appearing as expired 14CO2 in both humans and guinea pigs suggests
      that there is potential, although small, for xylose oxidation. It is yet to be
      determined if pigs develop increased xylose metabolic capacity with increased
      adaptation time to diets supplemented with xylose or xylanase. Overall, xylose
      appears to be poorly utilized by the pig, but it is important to consider that
      only one study has been reported which supplemented D-xylose dietary
      concentrations lower than 5%. Thus, more comprehensive studies testing xylose
      metabolic effects at dietary concentrations more relevant to swine nutrition are
      warranted.

PMID- 29340151
TI  - Reference values for spirometry in elderly individuals: a cross-sectional study
      of different reference equations.
AB  - Background: Spirometry is the single most important test for the evaluation of
      respiratory function. The results are interpreted by comparing measured data with
      predicted values previously obtained from a reference population. Reference
      equations for spirometry have been discussed previously. The aim of this study
      was to compare reference values based on National Health and Nutrition Assessment
      Survey (NHANES III), European Community of Steel and Coal (ECSC), and Global Lung
      Initiative (GLI) equations in an elderly sample population. Methods: Subjects
      from the Geriatric Study on Health Effects of Air Quality in elder care centres
      who met the inclusion criteria were enrolled. Spirometry was performed according
      to international guidelines. The forced vital capacity, forced expiratory volume
      in 1 s, and FEV1/FVC ratio were reported as percentages of the predicted value,
      and the lower limit of normality was calculated. Results: Out of 260 elderly
      patients, 69.6% were women; the mean age was 83.0 +/- 6.46 years with an age
      range of 65-95 years. The lowest %FVC and %FEV1 values were obtained using the
      GLI reference equations. However, when NHANES III equations were used, the
      FEV1/FVC ratio was higher than ratios obtained from GLI and ECSC equations. The
      prevalence of airway obstruction was highest using ECSC equations, while GLI
      equations demonstrated more restrictive defects. Conclusions: The present study
      showed meaningful differences in the reference values, and consequently, in the
      results obtained using NHANES III, ECSC, and GLI reference equations. The
      spirometry interpretation was also influenced by the reference equations used.

PMID- 29340152
TI  - Impact of gas emboli and hyperbaric treatment on respiratory function of
      loggerhead sea turtles (Caretta caretta).
AB  - Fisheries interactions are the most serious threats for sea turtle populations.
      Despite the existence of some rescue centres providing post-traumatic care and
      rehabilitation, adequate treatment is hampered by the lack of understanding of
      the problems incurred while turtles remain entrapped in fishing gears. Recently
      it was shown that bycaught loggerhead sea turtles (Caretta caretta) could
      experience formation of gas emboli (GE) and develop decompression sickness (DCS)
      after trawl and gillnet interaction. This condition could be reversed by
      hyperbaric O2 treatment (HBOT). The goal of this study was to assess how GE
      alters respiratory function in bycaught turtles before recompression therapy and
      measure the improvement after this treatment. Specifically, we assessed the
      effect of DCS on breath duration, expiratory and inspiratory flow and tidal
      volume (VT), and the effectiveness of HBOT to improve these parameters. HBOT
      significantly increased respiratory flows by 32-45% while VT increased by 33-35%
      immediately after HBOT. Repeated lung function testing indicated a temporal
      increase in both respiratory flow and VT for all bycaught turtles, but the
      changes were smaller than those seen immediately following HBOT. The current
      study suggests that respiratory function is significantly compromised in bycaught
      turtles with GE and that HBOT effectively restores lung function. Lung function
      testing may provide a novel means to help diagnose the presence of GE, be used to
      assess treatment efficacy, and contribute to sea turtle conservation efforts.

PMID- 29340153
TI  - Temporal migration patterns between natal locations of ruby-throated hummingbirds
      (Archilochus colubris) and their Gulf Coast stopover site.
AB  - Background: Autumn latitudinal migrations generally exhibit one of two different
      temporal migration patterns: type 1 where southern populations migrate south
      before northern populations, or type 2 where northern populations overtake
      southern populations en route. The ruby-throated hummingbird (Archilochus
      colubris) is a species with an expansive breeding range, which allows
      opportunities to examine variation in the timing of migration. Our objective was
      to determine a relationship between natal origin of ruby-throated hummingbirds
      and arrival at a Gulf coast stopover site; and if so, what factors, such as
      differences in body size across the range as well as the cost of migration, might
      drive such a pattern. To carry out our objectives, we captured hummingbirds at a
      coastal stopover site during autumn migration, at which time we collected
      feathers from juveniles for analysis of hydrogen stable isotopes. Using the
      hydrogen stable isotope gradient of precipitation across North America and
      published hydrogen isotope values of feathers from populations of breeding ruby
      throated hummingbirds, we assigned migrants to probable natal latitudes. Results:
      Our results confirm that individuals from across the range (30-50 degrees  N)
      stopover along the Gulf of Mexico and there is a positive relationship between
      arrival day and latitude, suggesting a type 1 migration pattern. We also found no
      relationship between fuel load (proxy for migration cost) or fat-free body mass
      (proxy for body size) and natal latitude. Conclusions: Our results, coupled with
      previous work on the spatial migration patterns of hummingbirds, show a type 1
      chain migration pattern. While the mechanisms we tested do not seem to influence
      the evolution of migratory patterns, other factors such as resource availability
      may play a prominent role in the evolution of this migration system.

PMID- 29340154
TI  - The impact of sepsis, delirium, and psychological distress on self-rated
      cognitive function in ICU survivors-a prospective cohort study.
AB  - Background: Many intensive care unit (ICU) survivors develop psychological
      problems and cognitive impairment. The relation between sepsis, delirium, and
      later cognitive problems is not fully elucidated, and the impact of psychological
      symptoms on cognitive function is poorly studied in ICU survivors. The primary
      aim of this study was to examine the relationship between sepsis, ICU delirium,
      and later self-rated cognitive function. A second aim was to investigate the
      association between psychological problems and self-rated cognitive function 3
      months after the ICU stay. Methods: Patients staying more than 24 h at the
      general ICU at the Karolinska University Hospital Solna, Stockholm, Sweden, were
      screened for delirium with the Confusion Assessment Method-ICU (CAM-ICU) during
      their ICU stay. Sepsis incidence and severity were recorded. Three months later,
      216 patients received the Cognitive Failures Questionnaire (CFQ), Hospital
      Anxiety and Depression Scale (HADS), and Post-Traumatic Stress Symptoms-10 (PTSS
      10) questionnaires via postal mail. Results: One hundred twenty-five patients
      (60%) responded to all questionnaires. Among respondents, the incidence of severe
      sepsis or septic shock was 42%. The overall incidence of delirium was 34%.
      Patients with severe sepsis/septic shock had a higher incidence of delirium, with
      an odds ratio (OR) of 3.7 (95% confidence interval (CI), 1.7-8.1). Self-rated
      cognitive problems 3 months post-ICU were found in 58% of the patients. We did
      not find any association between sepsis or delirium and late self-rated cognitive
      function. However, there was a correlation between psychological symptoms and
      self-rated cognitive function, with the strongest correlation between PTSS-10
      scores and CFQ scores (r = 0.53; p < 0.001). Conclusions: ICU delirium is more
      common in severely septic/septic shock patients. In our cohort, neither severe
      sepsis nor ICU delirium was associated with self-rated cognitive function 3
      months after the ICU stay. Ongoing psychological symptoms, particularly post
      traumatic stress was associated with worse self-rated cognitive function.
      Psychological symptoms need to be taken into account when assessing cognitive
      function in ICU survivors.

PMID- 29340155
TI  - Preservation of renal function by intensive glycemic control.
AB  - : We report the case of a 67-year-old Japanese woman with type 1 diabetes
      mellitus. At 47 years of age, her hemoglobin A1c (HbA1c) was 10.0%, and she had
      overt nephropathy. The first renal biopsy yielded a diagnosis of diabetic
      nephropathy. Intensive glycemic control was initiated and her HbA1c improved to
      6.0%. Renal dysfunction showed no progression for 15 years. At 62 years of age, a
      second renal biopsy was performed. Glomerular lesions did not show progression
      but tubulointerstitial fibrosis and vascular lesions showed progression compared
      with the first biopsy. Intensive glycemic control can prevent the progression of
      glomerular lesions, but might not be effective for interstitial and vascular
      lesions. Learning points: Intensive control of blood glucose can prevent the
      progression of glomerular lesions.Intensive control of blood glucose may not be
      able to prevent progression of interstitial and vascular lesions.CSII reduces
      HbA1c without increasing the risk of hypoglycemia.

PMID- 29340156
TI  - Hepatotoxicity in hyperthyroid patient after consecutive methimazole and
      propylthiouracil therapies.
AB  - : Methimazole (MMI) and propylthiouracil (PTU) are widely used antithyroid drugs
      (ATD) that have been approved for the treatment of hyperthyroidism.
      Hepatotoxicity may be induced by these drugs, though they exert dissimilar
      incidence rates of hepatotoxicity and, possibly, with different underlying
      pathogenic mechanisms. We report the case of a 55-year-old woman with no relevant
      medical history diagnosed with hyperthyroidism due to Graves' disease, who
      developed two episodes of acute hepatitis concurrent with the consecutive
      administration of two different ATDs, first MMI and then PTU. Given the
      impossibility of administering ATDs, it was decided to perform a total
      thyroidectomy because the patient was found to be euthyroid at that point.
      Pathological anatomy showed diffuse hyperplasia and a papillary thyroid
      microcarcinoma of 2 mm in diameter. Subsequent clinical check-ups were normal.
      This case suggests the importance of regular monitoring of liver function for
      hyperthyroid patients. Due to the potential severity of this side effect, it is
      recommended to determine baseline liver function prior to initiation of
      treatment. Learning points: We present a rare case of two acute hepatitis
      episodes concurrent with two different consecutive ATD therapies.Our results
      highlight the relevance of a liver function monitoring during the treatment with
      MMI or PTU.A baseline assessment of the liver function before starting an ATD
      treatment should be recommendable.

PMID- 29340157
TI  - Hypocalcemia due to 22q11.2 deletion syndrome diagnosed in adulthood.
AB  - : Chromosome 22q11.2 deletion syndrome (22q11.2DS) is a genetic syndrome that may
      present with hypocalcemia due to primary hypoparathyroidism (PH) at any age. We
      report a new diagnosis of 22q11.2DS in a 57-year-old man who presented with
      symptomatic hypocalcemia. It is important to consider genetic causes of
      hypocalcemia due to PH regardless of age. Learning points: It is important to
      discard genetic cause of primary hypoparathyroidism in a patient without
      autoimmune disease or prior neck surgery.A new diagnosis of a hereditary disease
      has familial implications and needs genetic counselling.It is also important to
      discard other syndrome's comorbidities.

PMID- 29340158
TI  - Follicular thyroid cancer avid on C-11 Methionine PET/CT.
AB  - : A case of follicular thyroid cancer with intense focal Methionine uptake on 11C
      Methionine PET/CT is reported here. The use of 11C-Methionine PET in
      differentiated thyroid cancer is currently being investigated as a surrogate
      tracer compared to the more widely used 18F-FDG PET. This case illustrates the
      potential incremental value of this modality, not only in the localizing of
      parathyroid adenoma, but also indicating that 11C-Methionine PET might have a
      potential of increasing the pretest likelihood of thyroid malignancy in a cold
      nodule with highly increased Sestamibi uptake. Learning points: 11C-Methionine
      PET/CT and 18F-Fluorocholine PET/CT often visualizes the parathyroid adenoma in
      case of negative Tc-99m-MIBI SPECT/CT.A cold nodule in Tc-99m Pertechnetat
      thyroid scintigraphy with a negative Sestamibi scintigraphy has a very low
      probability of being malignant.However, the pretest likelihood of thyroid cancer
      in a cold nodule with increased Sestamibi uptake is low.11C-Methionine PET might
      have a potential incremental value in increasing the pretest likelihood of
      thyroid malignancy in a cold nodule with highly increased Sestamibi uptake.

PMID- 29340159
TI  - Recurrent lactic acidosis and hypoglycemia with inadvertent metformin use: a case
      of look-alike pills.
AB  - : Metformin is recommended as the first-line agent for the treatment of type 2
      diabetes. Although this drug has a generally good safety profile, rare but
      potentially serious adverse effects may occur. Metformin-associated lactic
      acidosis, although very uncommon, carries a significant risk of mortality. The
      relationship between metformin accumulation and lactic acidosis is complex and is
      affected by the presence of comorbid conditions such as renal and hepatic
      disease. Plasma metformin levels do not reliably correlate with the severity of
      lactic acidosis. We present a case of inadvertent metformin overdose in a patient
      with both renal failure and hepatic cirrhosis, leading to two episodes of lactic
      acidosis and hypoglycemia. The patient was successfully treated with hemodialysis
      both times and did not develop any further lactic acidosis or hypoglycemia, after
      the identification of metformin tablets accidentally mixed in with his supply of
      sevelamer tablets. Early initiation of renal replacement therapy is key in
      decreasing lactic acidosis-associated mortality. Learning points: When a toxic
      ingestion is suspected, direct visualization of the patient's pills is advised in
      order to rule out the possibility of patient- or pharmacist-related medication
      errors.Though sending a specimen for determination of the plasma metformin
      concentration is important when a metformin-treated patient with diabetes
      presents with lactic acidosis, complex relationships exist between metformin
      accumulation, hyperlactatemia and acidosis, and the drug may not always be the
      precipitating factor.Intermittent hemodialysis is recommended as the first-line
      treatment for metformin-associated lactic acidosis (MALA).An investigational
      delayed-release form of metformin with reduced systemic absorption may carry a
      lower risk for MALA in patients with renal insufficiency, in whom metformin
      therapy may presently be contraindicated.

PMID- 29340160
TI  - Stereotactic body radiation therapy for the treatment of oligoprogression on
      androgen receptor targeted therapy in castration-resistant prostate cancer.
AB  - Castration-resistant prostate cancer is an incurable disease. To date, six agents
      abiraterone, enzalutamide, docetaxel, cabazitaxel, radium-223 and sipuleucel-T-
      have shown clinical efficacy in phase III clinical trials, leading to their FDA
      approval. Patients are typically sequenced through most or all of these agents,
      and then eventually succumb to their disease. Development of new treatments
      remains an unmet need. We report a case of a patient who progressed on
      enzalutamide with a single enlarging metastatic lesion, was treated with ablative
      stereotactic body radiation therapy while maintaining the same systemic
      treatment, who then had durable complete remission. Our findings have important
      clinical implications and suggest novel clinical trials for this difficult to
      treat disease.

PMID- 29340161
TI  - Direct ICE imaging from inside the left atrial appendage during ablation of
      persistent atrial fibrillation.
AB  - We present the case of a 59-year-old patient with persistent atrial fibrillation,
      referred for atrial fibrillation ablation. The procedure was performed with the
      help of NAVX 3D mapping system (Saint Jude Medical) and iLAB Ultra ICE Plus
      ultrasound imaging catheter (Boston Scientific). The catheter permits cross
      sectional images perpendicular to catheter's long axis. From inside left atrial
      appendage (LAA) looks trabeculated, due to pectinate muscles running parallel to
      each other. The presence of a thrombus was excluded from the appendage. The
      contractility of LAA was also assessed using multiple frames recorded on
      videotape. Our case demonstrates that LAA's morphology and function can be
      directly assessed by intracardiac ultrasound with the probe inserted inside the
      appendage.

PMID- 29340162
TI  - Iatrogenic myocarditis-biomarkers, cardiovascular MRI and the need for early
      diagnosis.

PMID- 29340163
TI  - The simplest method to classify CAM lesions.
AB  - CAM lesions are now seen as a significant pathology that could cause
      osteoarthritis of the hip joint. Currently there is no gold standard for
      classifying these lesions. We aim to show a simple method for classifying these
      lesions based on shape and position. Using CT 3D reconstruction, 91 preoperative
      CT scans from patients who had undergone hip arthroscopy for femoroacetabular
      impingement, were reconstructed to produce 3D images. Two senior hip surgeons
      have devised a simple four type classification system from previous experience.
      The system highlights the position and shape of different CAM lesions present in
      patients. The two senior surgeons and one junior surgeon reviewed the scans
      individually to assess whether the system could be used at all levels of surgical
      experience. The two senior surgeons agreed on which type of CAM lesion was
      present in all 91 cases. Intra observer reliability scores for the senior
      surgeons were 0.90 and 0.91. The junior surgeon reviewed the scans and disagreed
      on eight cases. This gave a Kappa co-efficient score of 0.87, which confirms a
      reliable system. We believe this classification system is simple and
      reproducible. It will aid surgeons in pre and intra-operative management of CAM
      lesions. Surgeons will be able to select the optimal portal placement and resect
      less capsule depending on the exact CAM lesion identified. This will potentially
      reduce complications and improve outcomes in junior hip arthroscopy surgeons.

PMID- 29340164
TI  - The 'Hip Vacuum Sign'-a new radiographic phenomenon in femoro-acetabular
      impingement.
AB  - Femoro-acetabular impingement (FAI) is a frequent cause for groin pain in young
      and active patients. We discovered a so far undescribed radiographic phenomenon
      only visible in frog-leg lateral radiographs. The aim of this study was to
      describe this new radiological sign, to determine its prevalence in a symptomatic
      population and to investigate the correlation to a potential underlying
      pathology. We retrospectively reviewed all patients, who had been sent to our
      clinic between 2010 and 2012 for hip complaints. We excluded patients older than
      50 years and patients with advanced osteoarthritis. Two independent investigators
      blinded to clinical data independently examined all images for the presence,
      location and dimension of a vacuum phenomenon and a potential underlying hip
      pathology. We included 242 patients. 137 of them showed clinical and radiological
      signs of FAI. A hip vacuum phenomenon was identified in 20 of 242 patients (8%).
      Interestingly, all these patients showed distinct signs of femoro-acetabular
      impingement. In reference to this, the prevalence of the "Hip Vacuum Sign" was
      15% (20/137) in symptomatic patients with FAI. There was no correlation with age
      or gender. We identified a new radiological sign, the "Hip Vacuum Sign", in 15%
      of symptomatic patients with FAI. It was only visible in frog-leg lateral
      radiographs. We suggest that it represents a subluxation of the femoral head due
      to a lever mechanism between the femoral neck and the acetabular rim and is,
      therefore, a hint for a relevant femoro-acetabular impingement mechanism.

PMID- 29340165
TI  - Nitric oxide induced by Indian ginseng root extract inhibits Infectious Bursal
      Disease virus in chicken embryo fibroblasts in vitro.
AB  - Infectious Bursal Disease is a severe viral disease of chicken responsible for
      serious economic losses to poultry farmers. The causative agent, Infectious
      Bursal Disease virus, is inhibited by nitric oxide. Root extract of the Indian
      ginseng, Withania somnifera, inhibits Infectious Bursal Disease virus in vitro.
      Also, Withania somnifera root extract is known to induce nitric oxide production
      in vitro. Therefore, the present study was undertaken to determine if the
      inhibitory activity of Withania somnifera against Infectious Bursal Disease virus
      was based on the production of nitric oxide. We show that besides other
      mechanisms, the inhibition of Infectious Bursal Disease virus by Withania
      somnifera involves the production of nitric oxide. Our results also highlight the
      paradoxical role of nitric oxide in the pathogenesis of Infectious Bursal
      Disease.

PMID- 29340166
TI  - Withdrawal of antihypertensive therapy in people with dementia: feasibility
      study.
AB  - Background: This study explored the feasibility of a randomised controlled
      withdrawal trial of antihypertensive medication in normotensive people with
      dementia. Feasibility aspects included response, recruitment, exclusion and drop
      out rates, suitability of outcome measures, acceptability of study procedures and
      an indicative economic evaluation for a randomised controlled trial. Methods: A
      cohort study attempting the withdrawal of antihypertensive drugs where
      appropriate and a feasibility study of home-based blood pressure monitoring, in
      people with dementia treated for hypertension, was undertaken. Interviews with
      participants and carers and an indicative economic evaluation were also
      undertaken. Results: Three hundred and sixty-two primary care practices in the
      East Midlands were contacted of which only 41 (11% (95%CI 8-15%)) agreed to
      support the study. These 41 practices posted 940 letters to potential
      participants. Thirty participants were enrolled in the cohort study of whom 9
      were eligible for the antihypertensive withdrawal programme, 20 participated in a
      home blood pressure monitoring sub-group analysis and 12 took part in an
      interview study. Twenty-two of those enrolled in the cohort study were followed
      up at 6 months. The withdrawal programme was acceptable to participants and
      general practitioners (GPs). The study procedures including assessments and home
      blood pressure monitoring were acceptable to the participants and their carers.
      The economic evaluation was not possible. Conclusion: A withdrawal trial of
      antihypertensive medication in normotensive people with dementia may not be
      feasible in the UK because of low recruitment rates.

PMID- 29340167
TI  - Subcutaneous glucagon infusion and continuous glucose monitoring enable effective
      management of hypoglycemia in a patient with IGF-2-producing hemangiopericytoma.
AB  - Background: Ectopic insulin-like growth factor (IGF)-2 production is a rare
      complication of an array of epithelial and mesenchymal tumors, and can clinically
      manifest as life-threatening hypoglycemia. Case presentation: A 49-year-old woman
      with 13-year history of metastatic hemangiopericytoma, previously treated with
      multiple rounds of chemotherapy and palliative radiation, presented to the
      emergency department after a hypoglycemic seizure. On arrival, glucose was 18
      mg/dL (1.0 mmol/L) and required continuous dextrose infusion for maintenance
      within normal limits. Insulin was <2.0 MUU/mL, C-peptide 0.1 ng/mL, and beta
      hydroxybutyrate <0.2 mmol/L. Random cortisol was 21 MUg/dL; sulfonylurea screen,
      and insulin antibodies were negative. IGF-2 level was 1320 ng/mL; IGF-1 was
      within normal limits and IGF binding protein (BP)-3 suppressed. Dexamethasone,
      started at 6 mg twice daily, allowed discontinuation of the glucose infusion.
      Given concern for nocturnal hypoglycemia, and patient interest in steroid-sparing
      anti-hypoglycemic regimen, she was also started on overnight continuous
      subcutaneous glucagon infusion via insulin pump. She was discharged with
      instructions to maintain a diet high in complex carbohydrates during the day,
      while utilizing glucagon pump at night. She was also started on continuous
      glucose monitoring system (CGMS) with an alarm to warn of hypoglycemia. Glucagon
      infusion rate was later titrated based on CGMS readings. Abdominal CT revealed
      increasing size of a right upper quadrant mass not previously subjected to
      radiotherapy. After radiation to this area, hypoglycemia improved, allowing
      further glucagon titration. In parallel, IGF-2 level declined to 380 ng/mL.
      Conclusions: Ectopic IGF-2 production is a rare but often fatal complication of
      many cancers, and should be considered on the differential diagnosis in patients
      with malignancy and unexplained hypoglycemia. Once hypoglycemia is diagnosed,
      patients often have end-stage disease. While treatment of the causative tumor is
      the only definitive intervention, anti-hypoglycemia therapy is a life-saving,
      temporizing measure. In this case, the patient attained euglycemia and survived 3
      months after presentation before ultimately succumbing to other malignancy
      related complications. Given efficacy in management of hypoglycemia while
      awaiting definitive tumor-directed therapy, we submit nighttime subcutaneous
      glucagon infusion and CGMS are valuable additions to the physician's
      armamentarium in managing this condition.

PMID- 29340168
TI  - Evolution of the vertebrate neurocranium: problems of the premandibular domain
      and the origin of the trabecula.
AB  - The subdivision of the gnathostome neurocranium into an anterior neural crest
      derived moiety and a posterior mesodermal moiety has attracted the interest of
      researchers for nearly two centuries. We present a synthetic scenario for the
      evolution of this structure, uniting developmental data from living cyclostomes
      and gnathostomes with morphological data from fossil stem gnathostomes in a
      common phylogenetic framework. Ancestrally, vertebrates had an anteroposteriorly
      short forebrain, and the neurocranium was essentially mesodermal; skeletal
      structures derived from premandibular ectomesenchyme were mostly anterior to the
      brain and formed part of the visceral arch skeleton. The evolution of a one-piece
      neurocranial 'head shield' in jawless stem gnathostomes, such as galeaspids and
      osteostracans, caused this mesenchyme to become incorporated into the
      neurocranium, but its position relative to the brain and nasohypophyseal duct
      remained unchanged. Basically similar distribution of the premandibular
      ectomesenchyme is inferred, even in placoderms, the earliest jawed vertebrates,
      in which the separation of hypophyseal and nasal placodes obliterated the
      nasohypophyseal duct, leading to redeployment of this ectomesenchyme between the
      separate placodes and permitting differentiation of the crown gnathostome
      trabecula that floored the forebrain. Initially this region was very short, and
      the bulk of the premandibular cranial part projected anteroventral to the nasal
      capsule, as in jawless stem gnathostomes. Due to the lengthening of the
      forebrain, the anteriorly projecting 'upper lip' was lost, resulting in the
      modern gnathostome neurocranium with a long forebrain cavity floored by the
      trabeculae.

PMID- 29340169
TI  - Autoimmune retinopathy: A Review.
AB  - Autoimmune retinopathy (AIR) is a rare and still poorly understood immune
      mediated disease that may cause inflammation from circulating autoantibodies
      against the retina. It may be related to history of autoimmune disease in the
      patient or in a family member or the presence of neoplastic disease in the
      individual. The disease may be subdivided into paraneoplastic and non
      paraneoplastic AIR. When related to melanoma, it is referred to as MAR, and when
      related to other cancers, it is called CAR. The exact prevalence of AIR is
      unknown. It mainly affects older adults. Patients present with bilateral and
      asymmetric scotomas, photopsias, visual field defects, with rapidly progressive
      visual loss in late onset. In the initial stage, fundus examination is
      unremarkable, and in late stages, there is limited retinal epitheliopathy and
      vascular attenuation, with or without optic disc pallor, associated or not with
      intraocular inflammation and with no evidence of degenerative retinal disease. A
      clinical investigation with detailed anamnesis and laboratory tests should be
      performed to search for an associated neoplasm. Ophthalmologic and complementary
      examinations such as full-field electroretinogram, optical coherence tomography,
      visual field and fundus autofluorescence, help the diagnosis. Blood tests to
      search for autoantibodies should be requested. Management consists of prolonged
      immunosuppression, which may be combined with antioxidant vitamins. In general,
      the prognosis is uncertain, so the disease still needs to be better understood.
      More studies should be performed to improve diagnostic measures and define
      specific management that could preserve or even restore vision.

PMID- 29340170
TI  - From a national to an international journal: a new opportunity for the
      physiotherapy community.

PMID- 29340171
TI  - Passive standing as an adjunct rehabilitation intervention after stroke: a
      randomized controlled trial.
AB  - Background: Early physical rehabilitation enhances functional recovery in stroke
      survivors. Supported standing is a common adjunctive therapeutic practice in
      subjects with several central nervous diseases who are unable to stand actively.
      Data on the effect of supported positioning on standing frames in individuals
      with recent stroke are scarce and contradictory. Objectives: To verify if the
      addition of supported standing practice (SSP), delivered by means of a standing
      frame in two durations, to conventional physical therapy (CPT), may improve motor
      function, autonomy, and mobility in individuals with disability due to recent
      stroke. Methods: After baseline assessment, 75 participants with severe
      disability due to stroke, all receiving CPT, were randomly assigned to adjunctive
      20 or 40 min of SSP, or CPT only (control). Motor function, autonomy, and
      mobility were assessed before and after training, and three months later.
      Results: All participants assessed received the planned dose of intervention. No
      adverse events of SSP were detected. Most outcome measures improved from baseline
      through the end of treatment and in the follow-up in all groups; the extent of
      change was comparable across the three randomization groups. Conclusions: In this
      randomized trial, SSP was unable to provide any sizeable adjunctive benefit,
      above and beyond CPT, in subjects with recent stroke.

PMID- 29340172
TI  - Can experienced physiotherapists identify which patients are likely to succeed
      with physical therapy treatment?
AB  - Background: The purpose of the study was to determine if clinician predicted
      prognosis is associated with patient outcomes. Methods: The study was a secondary
      analysis of data that were collected in 8 physiotherapy outpatient clinics. Nine
      physiotherapists with post-graduate training in manual therapy (mean 20.3 years
      of experience) were asked at baseline to project the outcome of the patients
      evaluated. In total, 112 patients with low back (74 %) or neck (26 %) pain were
      treated pragmatically with interventions consisting of manual therapy,
      strengthening, and patient-specific education. Outcomes measures consisted of
      percent change in disability (Oswestry or Neck Disability Index), self-reported
      rate of recovery (0-100 %), and percent change in pain (numerical pain rating
      scale). Hierarchical logistic regression determined potential factors (clinician
      predicted prognosis score (1-10) at baseline, dichotomised as poor (1-6) and good
      (7-10); symptom duration categorised as acute, subacute or chronic; same previous
      injury (yes/no); baseline pain and disability scores; within-session improvement
      at initial visit (yes/no); and presence of >= one psychological factor)
      associated with meaningful changes in each of the three outcomes at discharge
      (disability and pain > 50 % improvement, rate of recovery >=82.5 % improvement).
      Results: Clinician predicted prognosis (OR 4.15, 95%CI = 1.31, 13.19, p = 0.02)
      and duration of symptoms (OR subacute 0.24, 95%CI = 0.07, 0.89, p = 0.03; chronic
      0.21, 95%CI = 0.05, 0.90, p = 0.04) were associated with rate of recovery,
      whereas only clinician predicted prognosis was associated with disability
      improvement (OR 4.28, 95 % CI 1.37, 13.37, p = 0.01). No variables were
      associated with pain improvement. Conclusions: Clinician predicted prognosis is
      potentially valuable for patients, as a good predicted prognosis is associated
      with improvements in disability and rate of recovery.

PMID- 29340173
TI  - Scoliosis: lower limb asymmetries during the gait cycle.
AB  - Background: Several studies indicate that the gait pattern of subjects suffering
      from scoliosis differs from the norm. However, there is conflicting evidence
      regarding the source of this discrepancy. Objective: To evaluate lower limb
      asymmetries in selected gait variables. Study design: A case-control study on
      lower limb asymmetries during gait which can be related to scoliosis. Methods: 31
      subjects with scoliosis (Study Group - SG) and an equal comparative control
      sample (Control Group - CG) of subjects underwent objective gait analysis with
      the Vicon(r) motion caption system whilst walking at a comfortable speed along
      the gait laboratory walkway. Analysis was performed at three levels: (1)
      Asymmetry in the SG against asymmetry in the CG, (2) Difference in magnitude of
      asymmetry between the SG and CG, and (3) Global mean values in the SG vs. CG. The
      Paired Student T-Test was used for intra-group analysis whilst the Independent
      Student T-Test was used for inter-group analysis of the selected parameters,
      which include temporal parameters (stride length, stride time, step length,
      individual step speed, speed of gait, cadence, swing-to-stance ratio), ground
      reaction force (peak GRF values during Loading and Propulsion phases, vertical
      component only) and electromyography (peak EMG values and their time of onset, as
      a percentage of the gait cycle) of two lower limb muscles (Gastronemius and
      Vastus Medialis). Results: No intra-group variation was found to be significant.
      However, the speed of gait was found to be significantly slower (p = 0.03) in
      scoliotic subjects when compared to the norm, as a result of the shorter stride
      length (p = 0.002 and longer stride time (p = 0.001) in the SG. Furthermore,
      there was statistical significance in the time of onset of EMG peaks for the
      Lateral Gastrocnemius (p = 0.02) with regards to inter-group difference in
      magnitude of lower limb asymmetry and global mean values. Conclusions: Scoliosis
      is a tri-planar deformity which has some impact on the gait pattern. This
      research study concludes that scoliotic subjects have a slower speed of gait due
      to a shorter stride length and a longer stride time, together with variations in
      the timing of muscle activation.

PMID- 29340174
TI  - Daily functional electrical stimulation during everyday walking activities
      improves performance and satisfaction in children with unilateral spastic
      cerebral palsy: a randomized controlled trial.
AB  - Background: The aim of this paper is to determine whether daily functional
      electrical stimulation (FES) is effective in improving self-perceptions of
      individually identified mobility performance problems in children with unilateral
      spastic cerebral palsy (USCP). We hypothesized that children receiving 8 weeks of
      FES treatment would have higher scores for self-perceived performance and
      satisfaction on the Canadian Occupational Performance Measure (COPM) for
      individually identified priorities than children not receiving FES. Methods:
      Thirty-two children (mean age 10 y 8 mo SD 3y 3mo) with USCP and a Gross Motor
      Function Classification System I or II were randomly assigned to the FES
      treatment group (8 weeks of daily FES) and control group (usual treatments).
      Participants were assessed at baseline (week 0), post treatment (week 8) and 6
      weeks follow-up (week 14). The primary outcome measures were self-perceived
      scores for performance and satisfaction of child- and parent-identified
      priorities assessed using the COPM post treatment and at follow-up. The secondary
      outcome measures were the categorization of the performance problems from the
      COPM and self-report responses according to the International Classification of
      Functioning Child and Youth version (ICF-CY). This was clinically important
      because an understanding of mobility performance problems for children with USCP
      is needed for family-centred service planning. Results: Performance scores (mean
      difference 1.6, 95 % CI 0.1 to 3.2, p = 0.034) and satisfaction scores post
      treatment (mean difference 2.4, 95 % CI 0.5 to 4.2, p = 0.004) were significantly
      higher in the treatment group than in the control group. There were no
      significant differences between the groups for performance scores at follow up,
      however there was a significant difference between the groups for satisfaction
      (mean difference 1.9, 95 % CI 0.1 to 3.8, p = 0.03) in favour of the treatment
      group. Priorities were identified across all levels of the ICF-CY but were most
      commonly identified in the activity and participation domains of the ICF-CY (79.5
      %). Conclusions: Daily FES applied during everyday walking is effective in
      addressing self-perceptions of individually identified priorities by improving
      the performance and satisfaction of functional skills after treatment. Trial
      registration: Australian New Zealand Clinical Trials Register
      ACTRN12614000949684. Registered 4 September 2014.

PMID- 29340175
TI  - Proprioceptive Based Training for stroke recovery. Proposal of new treatment
      modality for rehabilitation of upper limb in neurological diseases.
AB  - Background: The central nervous system (CNS) has plastic properties allowing its
      adaptation through development. These properties are still maintained in the
      adult age and potentially activated in case of brain lesion. In the present study
      authors hypothesized that a significant recovery of voluntary muscle contraction
      in post stroke patients experiencing severe upper limb paresis can be obtained,
      when proprioceptive based stimulations are provided. Proprioceptive based
      training (PBT) is based on performing concurrent movements with both unaffected
      and affected arm, with the aim to foster motor recovery through some mutual
      connections of interhemispheric and transcallosal pathways. The aim of this pre
      post pilot study was to evaluate the feasibility of PBT on recovery of voluntary
      muscle contraction in subacute phase after stroke. Methods: The treatment lasted
      1 h daily, 5 days per week for 3 weeks. The PBT consisted of multidirectional
      exercises executed synchronously with unaffected limb and verbal feedback. The
      Medical Research Council scale (MRC), Dynamometer, Fugl-Meyer Upper Extremity
      scale (F-M UE), Functional Independence Measure scale (FIM) and modified Ashworth
      scale were administered at the beginning and at the end of training. Statistical
      significance was set at p < 0.05. Results: Six patients with severe paresis of
      the upper limb within 6 months after stroke were enrolled in the study (5
      ischemic and 1 hemorrhagic stroke, 3 men and 3 women, mean age 65.7 +/- 8.7
      years, mean distance from stroke 4.1 +/- 1.5 months) and all of them well
      tolerated the training. The clinical changes of voluntary muscle contraction
      after PBT were statistically significant at the MRC scale overall (p = 0.028),
      and dynamometer assessment overall (p = 0.028). Each patient improved muscle
      contraction of one or more muscles and in 4 out of 6 patients voluntary active
      movement emerged after therapy. The functional outcomes (i.e. F-M UE and FIM) did
      not show significant change within group. Conclusions: The findings of this
      preliminary research revealed that PBT may be a feasible intervention to improve
      the motricity of upper limb in stroke survivors.

PMID- 29340176
TI  - To sit or stand? A preliminary, cross sectional study to investigate if there is
      a difference in glenohumeral subluxation in sitting or standing in people
      following stroke.
AB  - Background: Glenohumeral subluxation (GHS) is a common symptom following stroke.
      Many therapists postulate that GHS may be reduced if the base of support (BOS) is
      reduced and the centre of mass (COM) is raised as this requires greater postural
      muscle activity. However, there is little empirical evidence to support this
      practice. Objective: The aim of this preliminary study was to investigate if the
      amount of GHS alters from sitting to standing. Study design: A cross sectional,
      within-subject design in a convenience sample of 15 stroke patients with GHS was
      utilised. Methods: A prospective design was used with a single blinded tester who
      assessed GHS using the calliper method in sitting, standing and on return to
      sitting. Friedman and post hoc Wilcoxon tests showed that GHS was significantly
      reduced in standing compared to sitting (p <0.05) but this reduction was not
      maintained on return to sitting (p = 0.25). Conclusions: The results of this
      study are limited by its small size. However, these results indicate that
      reducing BOS during rehabilitation may improve GHS after stroke. Whilst the
      maintenance of benefit is not established, these findings suggest that reducing
      BOS as part of treatment may help patients with GHS. Further research is now
      required to replicate these results in a larger sample and to directly examine
      shoulder muscle activity to investigate which muscles may influence GHS in
      response to changing BOS. Future work could also aim to determine whether the
      reduction in GHS was directly attributable to a reduced BOS or the effort
      associated with moving from sitting to standing.

PMID- 29340177
TI  - Finite helical axis for the analysis of joint kinematics: comparison of an
      electromagnetic and an optical motion capture system.
AB  - Background: The analysis of joints kinematics is important in clinical practice
      and in research. Nowadays it is possible to evaluate the mobility of joints in
      vivo with different motion capture techniques available in the market. Optical
      systems use infrared cameras and reflective markers to evaluate body movements,
      while other systems use electromagnetic fields to detect position and orientation
      of sensors. The aim of this study was the evaluation of two motion capture
      systems based on different technologies (optical and electromagnetic) by
      comparing the distribution of finite helical axis (FHA) of rotation during
      controlled rotations of an object in different positions. Methods: The
      distribution of position and angle errors of the FHA were extracted by optical
      and electromagnetic system recordings during a controlled rotation of a low
      friction stool in different positions in a controlled environment. Results: The
      optical motion capture system showed lower angle and position errors in the
      distribution of FHA while the electromagnetic system had higher errors that
      increased with increasing distance from the antenna. Conclusions: The optical
      system showed lower errors in the estimation of FHA that could make it preferable
      with respect to electromagnetic systems during joint kinematics.

PMID- 29340178
TI  - Factors associated with citation rate of randomised controlled trials in
      physiotherapy.
AB  - Background: Despite the use of citation rate as a measure of quality of research
      is strongly criticized and debated, it remain a widely used method to evaluate
      performances of researchers, articles and journals. The aim of this study was to
      test which factors are associated with citation rate of Randomised Controlled
      Trials (RCTs) published on the physiotherapy field. Methods: All RCTs abstracted
      in the Physiotherapy Evidence Database (PEDro), indexed in Scopus database and
      published in 2008 were included. PEDro score, language of publication, indexing
      in PubMed database, type of access to articles, subdiscipline, the number of
      authors, the country where the study was performed, the type of institution where
      the study was conducted and the number of centres involved in the study
      (multicentric vs single-centre). and the 2013 5-year impact factor of the
      publishing journals were considered as independent variables. Citation rate until
      December 2013 was extracted from Scopus database and used as dependent variable.
      Results: Six hundred and nineteen RCTs, published in 283 journals, were included
      and analysed. The 5-year impact factor was the strongest variable associated with
      the citation rate and explained approximately 50 % of the variance, and the
      number of authors explained an additional small part (about 1 %) of variability.
      The other variables were excluded from the model. Conclusions: The study
      highlights that 5-year Impact Factor, not accessibility (language of publication,
      indexing in PubMed database or the type of access to articles) or reported
      quality (PEDro score), is a strong predictor of the number of citations for RCTs
      in the physiotherapy field. Our findings support the increasingly widespread idea
      that citation analysis does not reflect the scientific merit of the cited work,
      at least in terms of reported quality.The results of this study need to be
      confirmed with a publication window larger than one year.

PMID- 29340179
TI  - Comparative efficacy of three active treatment modules on psychosocial variables
      in patients with long-term mechanical low-back pain: a randomized-controlled
      trial.
AB  - Background: Psychosocial factors precipitate and perpetuate the risk of
      developing long-term Low-Back Pain (LBP) with resultant disability. However,
      management of psychosocial aspects of LBP still remains a major challenge. This
      study investigated the effect of static or dynamic back extensors endurance
      exercise on psychosocial variables of Fear-Avoidance Behaviour (FAB), Pain Self
      Efficacy Belief (PSEB) and Back Pain Consequences Belief (BPCB) in patients with
      LBP. Methods: A randomized-controlled trial of 67 patients assigned into McKenzie
      Protocol (MP) group (n = 25), MP and Static Endurance Exercise Group (MPSEEG; n =
      22); and MP and Dynamic Endurance Exercise Group (MPDEEG; n = 20) was carried
      out. Treatment was applied thrice weekly for eight weeks. Results: The groups
      were comparable in general and baseline psychosocial parameters (p > 0.05). The
      different regimens had significant effects on all outcome parameters across
      baseline, 4th and 8th week (p < 0.05). The regimens were comparable in mean
      change scores on BPCB and FAB at the 4th and 8th week respectively (p > 0.05).
      MPDBEEG had higher mean change in PSEB at the 4th and 8th week respectively.
      Conclusions: McKenzie Protocol alone, or in combination with static or dynamic
      back extensors endurance exercise has comparable effect on FAB, PSEB and BPCB in
      patients with LBP. The addition of dynamic endurance exercise to the MP led to
      significantly higher positive effects on PSEB.

PMID- 29340180
TI  - Interrater and intrarater reliability and minimal detectable change of the
      Wisconsin Gait Scale when used to examine videotaped gait in individuals post
      stroke.
AB  - Background: Often, interventions targeting the kinematic and temporal and spatial
      changes in gait commonly seen after a stroke are based on observations of
      walking. Having the capacity to objectively identify such changes and track
      improvements over time using reliable and valid measures is important. The
      Wisconsin Gait Scale (WGS), which is comprised of 14 items, was developed
      specifically to examine and document gait changes occurring after a stroke. The
      purpose of the study was to explore the interrater and intrarater reliability and
      minimal detectable change (MDC) of the WGS when used by physical therapists to
      examine gait in adults post-stroke. Methods: Fourteen physical therapists from 3
      different acute inpatient rehabilitation centers rated videotapes of the gait of
      6 adults post-stroke using the WGS. To minimize subject variability from fatigue,
      videotapes created by using 4 cameras provided right and left lateral, anterior,
      and posterior views of walking on a level surface. One complete ambulation trial
      from each subject post-stroke, which included 4 views of the same ambulation
      trial, was examined by the licensed physical therapists using the WGS. An
      opportunity was provided to review the tool and a practice trial was performed
      using an additional videotape not included in the analysis. Gait was examined on
      2 different occasions separated by a period of approximately 21 days to minimize
      the effects of recall bias. Intraclass Correlation Coefficients (ICC) were used
      to examine the interrater and intrarater reliability of the WGS. Results:
      Interrater (ICC = 0.83) and intrarater (ICC = 0.91) reliability were both good.
      The standard error of the measurement (SEM) was 1.47 and the MDC95 was 4.24.
      There was no statistically significant difference between the scores on the WGS
      when comparing the 2 different sessions. Conclusions: The WGS shows promise as an
      instrument that can make observational gait analysis more reliable. High
      intrarater reliability and low SEM suggests that the WGS is stable when
      administered across multiple sessions by the same rater. The ICC for interrater
      reliability was also good, which suggests that multiple examiners can effectively
      use the instrument. With minimal training, the physical therapists in the study
      were able to produce highly reliable results using the WGS to objectively
      document gait dysfunction.

PMID- 29340181
TI  - Effects of walking on bilateral differences in spatial attention control: a cross
      over design.
AB  - Background: Walking requires a high attentional cost for balance control and
      interferes with the control of attention. However, it is unclear whether the
      performance of visual spatial attention control, which is one of the functions of
      attention control, is also decreased during walking. In addition, although
      previous studies have shown right-hemispheric dominance and lower ability of left
      side visual spatial attention control during sitting, it remains unknown whether
      walking accentuates bilateral differences in visual spatial attention control. We
      tested the hypothesis that walking interferes with visual spatial attention
      control on both sides and accentuates its bilateral differences. Methods: Twenty
      healthy right-handed subjects (24.3 +/- 2.0 years) participated in this study.
      Subjects performed a random stimulus-response compatibility (SRC) task during
      both sitting and walking situations. To evaluate the effects of walking, reaction
      time was measured on both sides for the two situations. In comparison to the both
      situations (sitting and walking), the amount of change of the SRC effect on both
      sides was used. In the comparing the bilateral difference (left and right), the
      difference of the SRC effect was evaluated in each situation. The paired t-test
      was applied to both comparisons for statistical analysis. Results: The SRC effect
      on both sides during walking was significantly larger than during sitting (P <
      0.05). In addition, walking significantly accentuated the bilateral differences
      in visual spatial attention control (P < 0.05). Conclusions: These results
      suggest that walking affects the performance of visual spatial attention control
      on both sides and accentuates its bilateral differences. These results have
      implications for development of practice methods of gait disorder with higher
      brain dysfunction.

PMID- 29340182
TI  - Differences in personal and lifestyle characteristics among Zimbabwean high
      school adolescents with and without recurrent non-specific low back pain: a two
      part cross-sectional study.
AB  - Background: Recurrent non-specific low back pain (NSLBP) is increasingly becoming
      common among adolescents worldwide. A recent study in Zimbabwe showed a
      relatively high prevalence (28.8 %) among high school students. Influential
      associated factors, however, remain unclear. This is a significant shortcoming.
      The aim was to determine personal or lifestyle-related factors associated with
      recurrent NSLBP among high school adolescents in Harare, Zimbabwe. Methods: This
      study was part of a large epidemiological study conducted in two continuous
      parts. Part one sought to determine self-reported associated factors among 532
      participants (mean age =16 +/- 1.72 years) drawn randomly from selected
      government schools using a reliable and content-validated questionnaire (Kappa
      coefficient, k = 0.32-1). Part two purposively identified adolescents (N = 64,
      median age =17 years, interquartile range, IQR = 15-18 years) with a history of
      'severe' recurrent NSLBP from part one based on a specific eligibility criteria
      and compared body mass index, relative school bag weight and hamstring
      flexibility with matched adolescents without NSLBP. Data was analysed using
      Statistica version 11. Independent t-tests or chi2 tests of association were used
      for continuous and categorical data, respectively. The statistical significance
      was set at p < .05. Results: Recurrent NSLBP was associated with self-reported
      factors such as perceptions of a heavy school bag [chi2 (1) = 85.9, p < 0.001]. A
      significant proportion of adolescents with recurrent NSLBP spent over 30 min
      carrying the school bag to and from school [chi2 (1) =32.2, p < 0.001]. It was
      also associated with prolonged sitting (p < 0.001), not playing sports [chi2 (1)
      =5.85, p = 0.02] and tight hamstrings [chi2 (1) =7.6, p = 0.006]. Conclusions:
      Although conclusions from this study are hesitant because of the cross-sectional
      nature of the study and the relatively small sample size in follow-up study,
      recurrent NSLBP is associated with perceptions of a heavy school bag, duration of
      school bag carriage, no sports participation, prolonged sitting on entertainment
      activities, and tight hamstrings. These findings add to the importance of
      promoting physical activity at school or home especially aimed at improving
      muscle flexibility.

PMID- 29340183
TI  - Action observation training to improve motor function recovery: a systematic
      review.
AB  - Following the discovery of Mirror Neuron System (MNS), Action Observation
      Training (AOT) has become an emerging rehabilitation tool to improve motor
      functions both in neurologic and orthopedic pathologies. The aim of this study is
      to present the state of the art on the use of AOT in experimental studies to
      improve motor function recovery in any disease. The research was performed in
      PubMed, PEDro, Embase, CINAHL and Cochrane Central Register of Controlled Trials
      (last search July 2015). Randomized controlled trials (RCTs) that analyse
      efficacy of AOT for recovery of motor functions, regardless of the kind of
      disease, were retrieved. The validity of the included studies was assessed using
      the Cochrane Collaboration tool for evaluating risk of bias. Twenty RCTs were
      eligible. Four studies showed AOT efficacy in improving upper limb functional
      recovery in participants with chronic stroke, two studies in sub-acute ones and
      one in acute ones. Six articles suggested its effectiveness on walking
      performance in chronic stroke individuals, and three of them also suggested an
      efficacy in improving balance. The use of AOT was also recommended in individuals
      with Parkinson's disease to improve autonomy in activities of daily living, to
      improve spontaneous movement rate of self-paced finger movements and to reduce
      freezing of gait. Other two studies also indicated that AOT improves upper limb
      motor function in children with cerebral palsy. The last two studies, showed the
      efficacy of AOT in improving motor recovery in postsurgical orthopedic
      participants. Overall methodological quality of the considered studies was
      medium. The majority of analyzed studies suggest the efficacy of AOT, in addition
      to conventional physiotherapy, to improve motor function recovery in individuals
      with neurological and orthopedic diseases. However, the application of AOT is
      very heterogeneous in terms of diseases and outcome measures assessed, which
      makes it difficult to reach, to date, any conclusion that might influence
      clinical practice.

PMID- 29340184
TI  - Aerosol delivery practice in Italian Cystic Fibrosis centres: a national survey.
AB  - Background: Physiotherapists (PTs) are ideally positioned to assist patients and
      families with inhalation therapies through monitoring, communication and
      education about available therapies and their proper use; indeed aerosoltherapy
      management is listed as part of Italian PTs' core competence and in the core
      syllabus for post-graduate training in respiratory physiotherapy. The aim of this
      study was to outline the involvement of Italian PTs working in Cystic Fibrosis
      (CF) centres in the aerosol delivery practice. Methods: Physiotherapist
      coordinators (n = 29) of all Italian CF centres were invited to participate in a
      cross-sectional survey and a semi-structured questionnaire was developed and sent
      by e-mail. Results: A response rate of 69 % was achieved. The majority of
      participants were woman and the overall mean professional experience was twenty
      years. Italian PTs are involved in the aerosol delivery practice, managing
      education, drug-device combination, dilution and mixing of drugs. Conclusions:
      Physiotherapists play a key role in the care of Italian CF patients; nevertheless
      the Italian Group of Physiotherapists might plan interventions to harmonize the
      aerosol delivery practice in Italian CF centres and to sustain continuing
      education.

PMID- 29340185
TI  - Physical fitness of Ghanaian physiotherapists and its correlation with age and
      exercise engagement: a pilot study.
AB  - Background: The physical job demands of physiotherapists require optimal level of
      physical fitness (PF), which is often not evaluated in practice. In this study,
      we assessed selected components of physical fitness of Ghanaian physiotherapists
      in relation to their sex, age and frequency of exercise participation. Methods:
      Physiotherapists practicing in four major hospitals within the Accra Metropolis
      of Ghana were enrolled into this cross-sectional survey. Three major components
      of physical fitness (flexibility, cardiorespiratory endurance and body
      composition) were assessed with sit and reach test, 3-min step test and BMI
      respectively. Unpaired sample t-test was used to determine differences in means
      of the three components of physical fitness betwwen males and females. Pearson
      correlation coefficient showed that frequency of exercise engagement and age of
      the participants correlated with the three components of physical fitness at p <
      0.05. Results: The study sample consisted of 40 participants, out of which 23 (58
      %) were females. The mean age was (31.5 +/- 1.4) years and majority 21 (52.5 %)
      was within the age range of 20-29 years. Respective mean scores for
      cardiorespiratory endurance, flexibility and BMI were (98.2 +/- 12.9 beat/min),
      (4.03 +/- 6.15 cm) and (23.3 +/- 3.4 kg/m2). Female participants were
      significantly more flexible than their male counterparts (5.7 +/- 5.3; 1.6 +/-
      6.6, p = 0.034). There was a positive and significant correlation between the age
      of the participants and BMI (r = 0.614 and p = 0.017). However, cardiorespiratory
      endurance was not significantly correlated with age and frequency of exercise
      engagement. Conclusions: The sampled physiotherapists had relatively low physical
      fitness compared to the age adjusted values. Age and sex are therefore crucial
      determinants whilst designing programmes aimed at promoting physical fitness in
      this group.

PMID- 29340187
TI  - Motor rehabilitation should be based on knowledge of motor control.
AB  - Neurorehabilitation is at a crossroads. Indeed, there is inconclusive, but
      promising evidence about clinical effectiveness of rehabilitation in the field of
      neurological impairments. Translating the new theories on motor control into
      clinical research may help to develop new treatment strategies and guide
      rehabilitation approaches. The concepts of synergy and the uncontrolled manifold
      hypothesis provide a strong theoretical framework to explain how the nervous
      system controls and coordinates movements, ensuring stability during daily
      actions. Moreover, this approach can increase the understanding of the neural
      control of action stability with implications for clinical practice and may help
      the development of new treatment strategies.

PMID- 29340188
TI  - At discharge gait speed and independence of patients provides a challenges for
      rehabilitation after total joint arthroplasty: an observational study.
AB  - Background: The level of functioning in people discharged from hospital after hip
      arthroplasty is very heterogeneous and prognostic factors are not fully
      understood. The aim of this study was to determine the mean level of autonomy
      achieved by such patients at discharge from hospital using the Iowa Level of
      Assistence (ILOA) scale as a measurement tool and to investigate the possible
      predictive factors of this autonomy. Methods: It was conducted a prospective
      cohort study including hip arthroplasty patients treated consecutively in 2012.
      Hip arthroplasty patients following fractures, revision surgery and partial
      replacement were excluded, as well as patients with concomitant neurologic or
      rheumatologic diseases or postoperative complications that did not allow to
      continue the rehabilitation program, and patients with a hospitalization of more
      than 7 days. During the last 24 h of hospital stay the physiotherapist filled in
      the ILOA scale and collected all data (age, gender, number of physiotherapy
      treatments, length of hospitalization). Statistical analysis (univariate and
      multivariate analysis) was performed between the variables collected and the ILOA
      Score. Results: The sample was composed of 167 patients. The mean score of the
      ILOA was 16.6 (+/-6.5) and gait speed had the poorest outcome 0.19 m/s - 0.43
      m/s. Multivariate analysis showed that older women are most at risk of not
      achieving good levels of autonomy. Conclusions: In hip arthroplasty patients at
      discharge from hospital gait speed is severely impaired. The challenge for
      rehabilitation should be to recover walking ability and efficiency starting from
      the early post-operative period. Gender- and age-tailored rehabilitation programs
      should be considered by placing particular attention on elderly women.

PMID- 29340189
TI  - A cross-sectional study investigating impressions and opinions of medical
      rehabilitation professionals on the effectiveness of the Ponseti method for
      treatment of clubfoot in Harare, Zimbabwe.
AB  - Background: The Ponseti method of managing clubfoot was introduced in Zimbabwe in
      2011. This followed massive training of health workers such as medical
      rehabilitation practitioners through a programme called the Zimbabwe Sustainable
      Clubfoot Programme. Today, the Ponseti method is the technique of choice for
      managing clubfoot in hospitals. However, since then, there is no published
      evidence documenting the efficacy and the relevance of the technique especially
      comparing to previously used methods. This is a significant shortcoming if
      sustainability issues are to be considered. Therefore, this study was designed to
      investigate the impressions and opinions of medical rehabilitation practitioners
      on the method in terms of its effectiveness, perceived challenges and possible
      recommendations for improvement of the technique application in their setting.
      Methods: A descriptive cross-sectional study was conducted targeting medical
      rehabilitation practitioners previously trained on the method and working in
      public or private clinics that offer clubfoot management in Harare. A
      questionnaire was self-administered to 41 participants who volunteered to
      participate in the study. Data from open-ended questions was analysed
      thematically. Statistica version 12 was used for analysis for quantitative data.
      Results: The Ponseti method was perceived as an effective method in the treatment
      of children with clubfoot by all the participants. All the participants 41 (100
      %) felt that the method was relevant because of better clinical outcomes. Amongst
      challenges faced when using Ponseti method, 25 (61 %) participants agreed that
      caregivers to the children with clubfoot were not compliant to treatment. A total
      of 22 (54 %) participants felt that lack of adequate insight by the caregivers of
      this new method was a challenge which hinder progress in treating clubfoot.
      Conclusions: The medical rehabilitation professionals in Harare, Zimbabwe trained
      to use the Ponseti technique for the management of clubfoot, perceived the method
      as an effective method resulting in better clinical outcome than previous
      methods. This probably highlights the need to continue training medical
      rehabilitation professionals so that there is widespread use of the technique in
      the country. However, there is need to increase awareness of the method among
      caregivers to improve compliance, which is key to successful rehabilitation of
      the clubfoot.

PMID- 29340190
TI  - Consequences and management of neck pain by female office workers: results of a
      survey and clinical assessment.
AB  - Background: Neck pain is common in office workers. However, the functional
      consequences of this pain to the individual and how they are managed are not well
      known. The objective of this study is understand the impact of neck pain and the
      strategies female office workers use to manage their pain while remaining at
      work. Methods: Female office workers with neck pain (n = 174) completed a survey
      about the impact of their neck pain, with 51 attending a university clinic for
      further assessment. Consequences of neck pain were evaluated with questions on
      self-reported work absence, workers' compensation claims, health care use, impact
      on work and leisure activity, and management strategies. Responses to survey
      questions were analysed using descriptive analyses. Results: The results showed
      that during the preceding 12 months, 57.5 % of participants had consulted a
      health professional due to neck pain; 42 % had reduced their leisure activities;
      22.4 % had reduced their work activity and 20.7 % had been absent from work. Only
      5.2 % had ever submitted a workers' compensation claim and 9 % indicated changing
      jobs due to neck pain. Of the 51 participants who attended for further
      assessment, 35.3 % indicated they 'self-managed' their neck pain with
      conventional medical strategies. Common strategies utilized were: prescription or
      over-the-counter medications (82.5 %), physiotherapy (64.7 %) and visiting their
      general medical practitioner (54.9 %). Conclusions: Although the severity of neck
      pain experienced by female office workers in this study was low, the impact on
      work and leisure was substantial. These workers tended to self-manage their pain
      by reducing work and/or leisure activity and utilizing passive coping strategies
      to remain at work. Physiotherapists are ideally suited to provide self-management
      strategies to ensure workers remain healthy while working.

PMID- 29340192
TI  - Use of social media among Italian physiotherapists: a new opportunity for the
      profession or an unfavorable trend toward guruism?
AB  - The advent of social media such as Facebook has introduced new opportunities for
      knowledge sharing and professional networking. Currently, little is known on how
      physiotherapists participate in virtual communities, and there are opposing views
      regarding the benefits and pitfalls of professional use of social media. In this
      letter, theoretical frameworks are proposed by analyzing the behavior of users
      and the post contents on Italian pages dedicated to physiotherapy. There is also
      an urgent need to evaluate whether virtual communities may improve final patient
      outcomes.

PMID- 29340191
TI  - Patient-reported outcome measures for non-specific neck pain validated in the
      Italian-language: a systematic review.
AB  - Background: Patient-reported outcome measures can improve the management of
      patients with non-specific neck pain. The choice of measure greatly depends on
      its content and psychometric properties. Most questionnaires were developed for
      English-speaking people, and need to undergo cross-cultural validation for use in
      different language contexts. To help Italian clinicians select the most
      appropriate tool, we systematically reviewed the validated Italian-language
      outcome measures for non-specific neck pain, and analyzed their psychometric
      properties and clinical utility. Methods: The search was performed in MEDLINE,
      EMBASE, CINAHL, Scopus, Web of Science, and Cochrane Library. All articles
      published in English or Italian regarding the development, translation, or
      validation of patient-reported outcome measures available in the Italian language
      were included. Two reviewers independently selected the studies, extracted data,
      and assessed methodological quality using the COSMIN checklist. Results: Out of
      4891articles screened, 66 were eligible. Overall, they were of poor or fair
      methodological quality. Four instruments measuring function and disability (Neck
      Disability Index, Neck Pain and Disability Scale, Neck Bournemouth Questionnaire,
      and Core Outcome Measures Index), and one measuring activity-related fear of
      movement (NeckPix(c)) were identified. Each scale showed some psychometric
      weaknesses or problems with functioning, and none emerged as a gold standard.
      Conclusions: Several patient-reported outcome measures are now available for
      assessing Italian people with non-specific neck pain. While the Neck Disability
      Index is the one most widely used, the Neck Bournemouth Questionnaire appears the
      most promising tool from a psychometric point of view.

PMID- 29340193
TI  - Implementation of the physical function ICU test tool in a resource constrained
      intensive care unit to promote early mobilisation of critically ill patients- a
      feasibility study.
AB  - Background: The shift of focus in outcome measures from mortality to assessment
      of functional status in intensive care unit (ICU) patients has resulted in the
      emergence of mobilisation of critically ill patients as a standard physiotherapy
      practice in most medium and high income countries. The aim of this study was to
      determine the feasibility of an early mobilisation program and to report on the
      changes in patient clinical outcomes following the intervention in a low income
      country. Methods: A prospective cohort study was carried out at one public
      hospital. An adult cohort of 35 patients was recruited within 24 h of being
      admitted into the unit, irrespective of ventilation method over a period of three
      months. An early mobilisation programme was implemented and prescribed using the
      Physical Function ICU Test (PFIT-s) which commenced in either the ICU or high
      dependent unit. Results: The median age of the 35 patients was 29 years (IQR = 24
      45 years). More than half of the patients had undergone surgery due to either
      gastrointestinal problems or obstetrical complications. A total of 94 out of a
      possible of 219 exercise sessions were delivered to the patients (43.0 %). The
      tool was implemented in 32 (91.4 %) patients on the initial PFIT-s measurement
      and 16 (45.7 %) of the patients required the assistance of two people to stand.
      The Initial PFIT-s mean score was 5.3 +/- 1.8. On final PFIT-s measurement, out
      of the 30 (85.7 %) patients seen, 15 (42.9 %) of the patients did not require any
      assistance to stand and the final PFIT-s mean score was 7.0 +/- 1.9. There was a
      significant difference in both the initial PFIT-s total score (t-value = 2.34, df
      = 30, p = .03) and the final PFIT-s score (t-value = 3.66, df = 28, p = .001)
      between males and females. During the treatment, no adverse event occurred in any
      of the patients. Conclusion: An early mobilisation program using PFIT-s was
      feasible and safe. There was a difference in functional capability based on
      gender, with males being more functionally active. Specific inclusion and
      exclusion criteria can lead to a delayed early mobilisation activities in ICU
      patients. Trial registration: Pan African Clinical Trials Registry
      PACTR201408000829202. Registered 15 August 2014.

PMID- 29340194
TI  - Measurement properties of the upright motor control test for adults with stroke:
      a systematic review.
AB  - Background: The Upright Motor Control Test (UMCT) has been used in clinical
      practice and research to assess functional strength of the hemiparetic lower limb
      in adults with stroke. It is unclear if evidence is sufficient to warrant its
      use. The purpose of this systematic review was to synthesize available evidence
      on the measurement properties of the UMCT for stroke rehabilitation. Methods:
      Electronic databases that indexed biomedical literature were systematically
      searched from inception until October 2015 (week 4): Embase, PubMed, Web of
      Science, CINAHL, PEDro, Cochrane Library, Scopus, ScienceDirect, SPORTDiscus,
      LILACS, DOAJ, and Google Scholar. All studies that had used the UMCT in the time
      period covered underwent hand searching for any additional study. Observational
      studies involving adults with stroke that explored any measurement property of
      the UMCT were included. The COnsensus-based Standards for the selection of health
      Measurement INstruments was used to assess the methodological quality of included
      studies. The CanChild Outcome Measures Rating Form was used for extracting data
      on measurement properties and clinical utility. Results: The search yielded three
      methodologic studies that addressed criterion-related validity and contruct
      validity. Two studies of fair methodological quality demonstrated moderate-level
      evidence that Knee Extension and Knee Flexion subtest scores were predictive of
      community-level and household-level ambulation. One study of fair methodological
      quality provided limited-level evidence for the correlation of Knee Extension
      subtest scores with a laboratory measure of ground reaction forces. No published
      studies formally assessed reliability, responsiveness, or clinical utility.
      Limited information on responsiveness and clinical utility dimensions could be
      inferred from the included studies. Conclusions: The UMCT is a practical
      assessment tool for voluntary control or functional strength of the hemiparetic
      lower limb in standing in adults with stroke. Although different levels of
      evidence suggest that the Knee Extension and Knee Flexion subtests may possess
      criterion and construct validity, the lack of published literature examining
      content validity, reliability, and responsiveness raises questions regarding the
      use of the UMCT in routine clinical practice. These key findings highlight the
      need to further investigate the UMCT's measurement properties toward enhancing
      its standardization.

PMID- 29340195
TI  - Combined treatment with paraffin, manual therapy, pegboard and splinting in a
      patient with post-traumatic stiff hand.
AB  - Background: The stiff hand is a still common, severe complication of hand
      injuries. Case presentation: We report here the case of a 56 year-old woman,
      professional goldsmith, who suffered a distal radius fracture of her right hand.
      The patient was treated with surgery followed by four weeks of immobilization,
      and developed a stiff hand. Physical examination showed mild inflammatory signs,
      pain and a major limitation in the extension and supination of the wrist, and in
      the mobility of the II, III, IV and V metacarpophalangeal (-5 degrees  and 32
      degrees  of average passive extension and flexion, respectively) and
      interphalangeal (-35 degrees  and 73 degrees  of average passive extension and
      flexion, respectively) joints. There was a lack of slip of the flexor tendons.
      The diagnosis of complex regional pain syndrome was considered although it could
      not be definitely established. After five months of adverse evolution the patient
      was referred to our center where a combined intervention with paraffin, manual
      therapy, prolonged active and passive stretch on a pegboard, and splinting was
      applied. After initiation of this therapy, a marked change in the evolution of
      the pain, the mobility and functionality of the hand was observed. At the end of
      the rehabilitation program the patient was able to fully resume her job.
      Conclusion: The present case illustrates the need of intensive treatment for post
      traumatic hand stiffness, and describes, as an original contribution, a combined
      intervention therapy including paraffin, manual therapy, pegboard and splinting.

PMID- 29340196
TI  - A therapist-focused knowledge translation intervention for improving patient
      adherence in musculoskeletal physiotherapy practice.
AB  - Background: Nonadherence to treatment remains high among patients with
      musculoskeletal conditions with negative impact on the treatment outcomes, use of
      personal and cost of care. An active knowledge translation (KT) strategy may be
      an effective strategy to support practice change. The purpose of this study was
      to deliver a brief, interactive, multifaceted and targeted KT program to improve
      physiotherapist knowledge and confidence in performing adherence enhancing
      activities related to risk, barriers, assessment and interventions. Methods: We
      utilised a 2-phase approach in this KT project. Phase 1 involved the development
      of an adherence tool kit following a synthesis of the literature and an iterative
      process involving 47 end-users. Clinicians treating patients with musculoskeletal
      conditions were recruited from two Physiotherapy and Occupational therapy
      national conferences in Canada. The intervention, based on the acronym SIMPLE
      TIPS was tested on 51 physiotherapists in phase 2. A pre- and post-repeated
      measures design was used in Phase 2. Graham's knowledge-to-action cycle was used
      as the conceptual framework. Participants completed a pre-intervention
      assessment, took part in a 1-h educational session and completed a post
      intervention assessment. A questionnaire was used to measure knowledge of
      evidence-based treatment adherence barriers, interventions and measures and
      confidence to perform evidence-based adherence practice activities. Data was
      analysed using descriptive statistics (frequency and percentage), Fisher's exact
      test and Wilcoxon Sign-Ranked tests. Results: Barriers and facilitators of
      adherence were identified under three domains (therapist, patient, health system)
      in phase 1. Seventy percent of the participants completed the questionnaire.
      Results indicated that 46.8% of respondents explored barriers including the use
      of behaviour change strategies and 45.7% reported that they measured adherence
      but none reported the use of validated outcomes. A significant improvement in
      post-self-efficacy scores for the four adherence enhancing activities was
      observed immediately after the workshop. Conclusion: The use of a multi-modal KT
      intervention is feasible in an educational setting. A brief interactive
      educational session was successfully implemented using a toolkit and caused a
      significant increase in physiotherapists' knowledge and confidence at performing
      adherence enhancing activities in the very short-term. Further testing of SIMPLE
      TIPS on long-term adherence practices could help advance best practices specific
      to treatment adherence in MSK practice.

PMID- 29340197
TI  - Hemodynamics and tissue oxygenation effects after increased in positive end
      expiratory pressure in coronary artery bypass surgery.
AB  - Background: Cardiac surgery is widely used in the treatment of cardiovascular
      diseases. However, several complications can be observed during the postoperative
      period. Positive end expiratory pressure (PEEP) improves gas exchange, but it
      might be related to decreased cardiac output and possible impairment of tissue
      oxygenation. The aim of this study was to investigate the hemodynamic effects and
      oxygen saturation of central venous blood (ScvO2) after increasing PEEP in
      hypoxemic patients after coronary artery bypass (CAB) surgery. Methods: Seventy
      post-cardiac surgery patients (CAB), 61 +/- 7 years, without ventricular
      dysfunction (left ventricular ejection fraction 57 +/- 2%), with hypoxemia
      (PaO2/FiO2 ratio <200) were enrolled. Heart rate, mean arterial pressure,
      arterial and venous blood samples were measured at intensive care unit and PEEP
      was increased to 12 cmH2O for 30 min. Results: As expected, PEEP12 improved
      arterial oxygenation and PaO2/FiO2 ratio (p < 0.0001). Reduction in ScvO2 was
      observed between PEEP5 (63 +/- 2%) and PEEP12 (57 +/- 1%; p = 0.01) with higher
      values of blood lactate in PEEP12 (p < 0.01). No hemodynamic effects (heart rate,
      mean arterial pressure, SpO2; p > 0.05) were related. Conclusion: Increased PEEP
      after cardiac surgery decreased ScvO2 and increased blood lactate, even with
      higher O2 delivery. PEEP did not interfere in hemodynamics status in CAB
      patients, suggesting that peripheral parameters must be controlled and measured
      during procedures involving increased PEEP in post-cardiac surgery patients in
      the intensive care unit.

PMID- 29340198
TI  - Content validity and test-retest reliability of a low back pain questionnaire in
      Zimbabwean adolescents.
AB  - Background: In Zimbabwe, a recent increase in the volume of research on recurrent
      non-specific low back pain (NSLBP) has revealed that adolescents are commonly
      affected. This is alarming to health professionals and parents and calls for
      serious primary preventative strategies to be developed and implemented
      forthwith. Early identification initiatives should be prioritised in order to
      curtail the condition and its progression. In an attempt to be proactive in
      minimising the prevalence of recurrent NSLBP, this study was conducted to
      evaluate the content validity and test-retest reliability of a survey
      questionnaire with the aim of proffering a valid and reliable questionnaire which
      can be used in non-clinical settings to identify adolescents with recurrent NSLBP
      in Harare, Zimbabwe and determine the possible factors associated with the
      condition. Methods: The study was conducted in two parts. The first part assessed
      content validity of the questionnaire using four experts derived from academia
      and clinical practice. The second part evaluated the reliability of the
      questionnaire among 125 high school-children aged between 13 and 19 years in a
      test-retest study. Results: Twenty-six (26) out of thirty questions in the
      questionnaire had an Item Content Validity index of 1.00, demonstrating complete
      agreement among content experts. Overall, the Scale Content Validity Index for
      the questionnaire was 0.97. Item completion for the reliability study was
      satisfactory. The questionnaire items had kappa values ranging from 0.17 (slight
      agreement) to 1 (perfect agreement). High levels of reliability were found for
      the questions on school bag use (k=0.94), sports participation (k=0.97), and
      lifetime prevalence (k=0.89). Conclusion: Excellent content validity and slight
      to perfect test-retest reliability was found for the Low Back Pain (LBP)
      questionnaire. These results are comparable to findings of other studies
      evaluating the psychometric properties of LBP questionnaires. Cognisant of the
      limitations of the study, the results of this study suggest that the LBP
      questionnaire could be used in local studies investigating LBP among adolescents
      although questions enquiring on functional limitations and sciatica may need
      further consideration.

PMID- 29340199
TI  - Depicting individual responses to physical therapist led chronic pain self
      management support with pain science education and exercise in primary health
      care: multiple case studies.
AB  - Background: Previous evidence suggests self-management programs for people with
      chronic pain improve knowledge and self-efficacy, but result in small to
      negligible changes in function. The purpose of this multiple case studies design
      was to describe the unique responses of six participants to a new self-management
      program aimed at improving function, to detail each component of the program, and
      to explore potential explanations for the varied trajectories of each of the
      participants. Case Presentation: Six participants who had been experiencing
      chronic pain for at least 5 years were included. All participants were enrolled 6
      weeks of ChrOnic pain self-ManageMent support with pain science EducatioN and
      exercise (COMMENCE). Participants completed an assessment at baseline, 7 weeks (1
      week follow-up), and 18 weeks (12-week follow-up). Each participant had a unique
      initial presentation and goals. Assessments included: function as measured by the
      Short Musculoskeletal Function Assessment - Dysfunction Index, how much
      participants are bothered by functional difficulties, pain intensity, fatigue,
      pain interference, cognitive and psychological factors associated with pain and
      disability, pain neurophysiology, self-efficacy, satisfaction, and perceived
      change. The self-management program was 6-weeks in length, consisting of one
      individual visit and one group visit per week. The program incorporated three
      novel elements not commonly included in self-management programs: pain
      neurophysiology education, individualized exercises determined by the
      participants' goals, and additional cognitive behavioural approaches.
      Participants were all satisfied with self-management support received. Change in
      function was variable ranging from 59% improvement to 17% decline. Two potential
      explanations for variances in response, attendance and social context, are
      discussed. Several challenges were identified by participants as barriers to
      attendance. Conclusions: A primary care self-management intervention including
      pain education and individualized exercise has potential to improve function for
      some people with chronic pain, although strategies to improve adherence and
      reduce barriers to participation may be needed to optimize the impact.

PMID- 29340200
TI  - A survey of physicians and physiotherapists on physical activity promotion in
      Nigeria.
AB  - Background: Effective control of non-communicable diseases and promotion of
      population-wide physical activity participation require the active engagement of
      health professionals. Physiotherapists and physicians, as part of their practice,
      routinely screen and assess physical activity status, and recommend health
      enhancing physical activity participation for their patients. This study aims to
      compare Nigerian physiotherapists and physicians' knowledge of physical activity
      message, role perception and confidence, perceived feasibility and barriers, and
      overall disposition to promoting physical activity in their practice. Methods: A
      total of 153 physicians and 94 physiotherapists recruited from 10 government
      hospitals in five states in Northern Nigeria completed a standardized physical
      activity promotion questionnaire that elicited information on the knowledge of
      physical activity, role perception and confidence, feasibility, and barriers to
      physical activity promotion. Descriptive and inferential statistics were used to
      analyze the data. Results: The physiotherapists and physicians were fairly
      knowledgeable on physical activity message (14.2 +/- 2.1/20), reported minimal or
      little barrier to physical activity promotion (23.7 +/- 3.1/30), perceived
      physical activity promotion as their role (13.0 +/- 1.8/15), were confident in
      their ability to discuss and recommend physical activity promotion (7.6 +/-
      1.6/10) and believed promoting physical activity was feasible for them (15.6 +/-
      2.6/20). However, over 40% of the physiotherapists and physicians do not know the
      correct dosage of physical activity that could confer health benefits to
      patients. The physicians showed better overall disposition to physical activity
      promotion than the physiotherapists (P = 0.048), but more physiotherapists than
      the physicians believed 'it is part of their role to suggest to patients to
      increase their daily physical activity' (95.7% vs 88.2%, P = 0.043) and were more
      'confident in suggesting specific physical activity programs for their patients'
      (87.2% vs 64.5%, P < 0.001). Conclusion: Physiotherapists and physicians in
      Nigeria demonstrated good disposition to promoting physical activity but many of
      them have knowledge deficits on the correct dosage required for better health for
      their patients. These health professionals can serve as good advocates for
      physical activity promotion in Nigeria, but many of them may require knowledge
      update on health enhancing physical activity for effective health promotion and
      primary prevention of non-communicable diseases.

PMID- 29340201
TI  - Developing the content of a locomotor disability scale for adults in Bangladesh:
      a qualitative study.
AB  - Background: Bangladesh has an estimated 17 million adults with disabilities. A
      significant proportion of them are believed to have locomotor disabilities. There
      are over 300 non-governmental organizations providing different types of
      rehabilitation services to them. However, there is no locally developed and
      validated locomotor disability measurement scale in Bangladesh. The purpose of
      this study was to develop a locomotor disability scale with disability indicators
      suitable for adults in Bangladesh. Methods: Semi-structured interviews were
      conducted with 25 purposively selected adults with locomotor disabilities to
      generate scale items. At the second stage, cognitive interviews were conducted
      with 12 purposively selected adults with locomotor disabilities in order to
      refine the measurement questions and response categories. Data were analysed
      using the framework technique- identifying, abstracting, charting and matching
      themes across the interviews. Results: For a locomotor disability scale, 70
      activities (disability indicators) were identified: 37 mobility activities, 9
      activities of daily living, 17 work/productivity activities and 7 leisure
      activities. Cognitive interviews revealed that when asking the respondents to
      rate their difficulty in performing the activities, instead of just mentioning
      the activity name, such as taking a bath or shower, a detailed description of the
      activity and response options were necessary to ensure consistent interpretation
      of the disability indicators and response options across all respondents.
      Conclusions: Identifying suitable disability indicators was the first step in
      developing a locomotor disability scale for adults in Bangladesh. Interviewing
      adults with locomotor disabilities in Bangladesh ensured that the locomotor
      disability scale is of relevance to them and consequently it has excellent
      content validity. Further research is needed to evaluate the psychometric
      properties of this scale.

PMID- 29340202
TI  - Exploring barriers to accessing physiotherapy services for stroke patients at
      Tema general hospital, Ghana.
AB  - Background: Physiotherapy has been shown to reduce the risk of disability among
      stroke patients. Poor adherence to physiotherapy can negatively affect outcomes
      and healthcare cost. However, very little is known about barriers especially to
      physiotherapy services in Ghana. The objective of this study was to assess the
      barriers to physiotherapy services for stroke patients at Tema General Hospital
      (TGH). The individual/personal and health system barriers to physiotherapy
      services at TGH were determined. Method: A cross-sectional study design was
      employed. A simple random sampling technique was used to recruit 207 respondents
      for a face-to-face interview. Interviewer-administered questionnaires were used
      to collect data on individual/personal barriers of respondents to physiotherapy
      services and were described using the Likert's scale. Health system barriers were
      assessed using a self-structured questionnaire which had section under the
      following heading: human factors, physiotherapy modalities, physical barriers and
      material/equipment factors. The time spent waiting for physiotherapy and attitude
      of physiotherapist towards patients; physiotherapy modality such as
      electrotherapy, exercise therapy and massage therapy among others were some of
      the indices measured. Respondents' adherence to Medication was assessed with the
      Morisky 8-item medication adherence questionnaire. Data were entered and analysed
      using Epi info 7 and STATA 12.0. Associations between the variables were
      determined using a chi-square test and logistic regression model was used to test
      the strength of associations between the independent and the dependent variables.
      The level of statistical significance was set at p < 0.05. Results: The results
      showed that majority (76.3%) of the respondents had economic barrier as their
      main individual/personal barrier to physiotherapy services. For medication
      adherence level, patients with low medication adherence level were about 21 times
      the odds of defaulting on accessing physiotherapy services five times or more as
      compared to those with medium adherence level (OR 20.63, 95% CI 8.96, 42.97). It
      was concluded in the study that individual/personal barriers of stroke patients
      were the significant barriers to accessing physiotherapy services at Tema General
      Hospital.

PMID- 29340203
TI  - Effectiveness of three modes of kinetic-chain exercises on quadriceps muscle
      strength and thigh girth among individuals with knee osteoarthritis.
AB  - Background: The study was designed to evaluate and compare the effectiveness of
      12-week open, closed and combined kinetic-chain exercises (OKCE, CKCE and CCE) on
      quadriceps muscle strength and thigh girth of patients with knee osteoarthritis
      (OA). Method: The randomized clinical trial involved ninety-six consecutive
      patients with knee OA who were randomly assigned to one of OKCE, CKCE or CCE
      groups. Participants' static quadriceps muscle strength (SQS), dynamic quadriceps
      muscle strength (DQS) and thigh girth (TG) were assessed using cable tensiometer,
      one repetition method and inelastic tape measure respectively at baseline and at
      the end of weeks 4, 8 and 12 of study. Results: The three groups were comparable
      regarding their demographic and dependent variables at baseline; there was
      significant time effect (p < 0.001each) as all three measures significantly
      increased over time from baseline to week 12 [mean difference: SQS: 3.30 (95% CI:
      2.52-4.08) N; DQS: 0.74 (95% CI: 0.45-1.02) N; TG: 1.32 (95% CI: 0.93-1.71) cm].
      The effect of intervention-time interaction was not significant (p > 0.05) for
      all three measures. Changes in SQS, DQS and TG between baseline and week 12 were
      also not significantly different (p > 0.05) among the three groups. Conclusion:
      All three exercise regimens are effective and demonstrate similar effects on
      quadriceps muscle strength and muscular trophism. Trial registration:
      NHREC/05/01/2008a. Registered 20th March, 2014 Retrospectively.

PMID- 29340204
TI  - Side alternating vibration training in patients with mitochondrial disease: a
      pilot study.
AB  - Background: Side alternating vibration training (SAVT) is a mechanical
      oscillation using a vibrating platform that simulates exercise. We hypothesized
      that patients with mitochondrial myopathies, who experience muscle weakness, may
      see an improvement in muscle power with SAVT. Methods: Patients with
      mitochondrial disease started either a treatment (SAVT) or control phase
      (standing without vibration) for 12 weeks, then 12 weeks of washout, and then a
      12-week cross-over. The main outcome measure was peak jump power (PJP). We
      compared this to a natural history cohort from clinic. Results: Seven out of 13
      patients completed at least 80% of their SAVT sessions and were analyzed. The
      DeltaPJP after the control phase was -2.7 +/- 1.7 W/kg (mean +/- SEM), SAVT was
      +2.8 +/- 0.6 W/kg (p < 0.05) and from the natural history cohort was -2.4 +/- 0.8
      W/kg/year. Conclusions: SAVT is well tolerated and may improve muscle power in
      mitochondrial disease patients.

PMID- 29340205
TI  - Physiotherapy in upper abdominal surgery - what is current practice in Australia?
AB  - Background: Upper abdominal surgery (UAS) has the potential to cause post
      operative pulmonary complications (PPCs). In the absence of high-quality research
      regarding post-operative physiotherapy management, consensus-based best practice
      guidelines formulated by Hanekom et al. (2012) are available to clinicians
      providing recommendations for post-UAS treatment. Such best practice guidelines
      have recommended that physiotherapists should be using early mobilisation and
      respiratory intervention to minimise risk of PPCs. However, recent evidence
      supports the implementation of mobilisation as a standalone treatment in PPC
      prevention, though the diversity in literature poses questions regarding ideal
      current practice. This project aimed to document and report the assessment
      measures and interventions physiotherapists are utilising following UAS,
      establishing whether current management is reflective of best practice guidelines
      and recent evidence. Results: An online survey was completed by 57 experienced
      Australian physiotherapists working with patients following UAS (35% survey
      response rate, 63% completion rate). On day one following UAS, when a patient's
      condition is not medically limited, most physiotherapists routinely mobilise.
      Additionally, routine chest treatment continues to be implemented, with only 23%
      (n = 11/47) of physiotherapists mobilising patients without accompanying specific
      respiratory intervention. Variability of screening tools used to identify post
      operative patients at high risk of PPC development was evident. Patient-dependent
      factors such as 'fatigue' and 'non-compliance' were among those identified as
      barriers to treatment, all influencing the commencement of treatment.
      Conclusions: Physiotherapists indicated that early mobilisation away from the
      bedside was the preferred post-operative treatment within the UAS patient
      population. Many continue to perform routine respiratory interventions despite
      recent literature suggesting it may provide no additional benefit to preventing
      PPCs. Current intervention choice is reflective of guidelines [1], however,
      recent literature has called this into question and more research needs to be
      done to establish if these recommendations are the most effective at reducing
      PPCs. Continued research is necessary to promote translation of knowledge to
      ensure physiotherapists are mobilising patients day one post-UAS. Likewise,
      future work should focus on identification of barriers, the strategies used to
      overcome limitations and the creation of a reliable and validated screening tool
      to ensure appropriate prioritisation and allocation of physiotherapy resources
      within the UAS patient population.

PMID- 29340206
TI  - How to diagnose cervicogenic dizziness.
AB  - Cervicogenic dizziness (CGD) is a clinical syndrome characterized by the presence
      of dizziness and associated neck pain. There are no definitive clinical or
      laboratory tests for CGD and therefore CGD is a diagnosis of exclusion. It can be
      difficult for healthcare professionals to differentiate CGD from other
      vestibular, medical and vascular disorders that cause dizziness, requiring a high
      level of skill and a thorough understanding of the proper tests and measures to
      accurately rule in or rule out competing diagnoses. Consequently, the purpose of
      this paper is to provide a systematic diagnostic approach to enable healthcare
      providers to accurately diagnose CGD. This narrative will outline a stepwise
      process for evaluating patients who may have CGD and provide steps to exclude
      diagnoses that can present with symptoms similar to those seen in CGD, including
      central and peripheral vestibular disorders, vestibular migraine, labyrinthine
      concussion, cervical arterial dysfunction, and whiplash associated disorder.

PMID- 29340207
TI  - Participation in physical activities for children with cerebral palsy:
      feasibility and effectiveness of physical activity on prescription.
AB  - Background: Children with cerebral palsy (CP) are less physically active and more
      sedentary than other children which implies risk factors for their physical and
      mental health. Physical activity on prescription (PAP) is an effective
      intervention to promote a lifestyle change towards increased physical activity in
      adults in general. Knowledge is lacking about the use of PAP in children with CP.
      Therefore, the aim of this study was to evaluate the feasibility of PAP for
      children with CP and its effectiveness on participation in physical activity and
      sedentary behaviour. Methods: Eleven children with CP, aged 7-11 years,
      participated in PAP, consisting of a written agreement between each child, their
      parents and the physiotherapist and based on Motivational Interviewing (MI),
      Canadian Occupational Performance Measure (COPM) and Goal Attainment Scaling
      (GAS). Individual goals, gross motor function and physical activity were assessed
      at baseline, at 8 and/or 11 months using COPM, GAS, logbooks, Gross Motor
      Function Measure (GMFM-66), physical activity questionnaires, physical activity
      and heart rate monitors and time-use diaries. At 8 and 11 months the feasibility
      of the intervention and costs and time spent for the families and the
      physiotherapist were evaluated by questionnaires. Results: The intervention was
      feasible according to the feasibility questionnaire. Each child participated in 1
      3 self-selected physical activities during 3-6 months with support from the
      physiotherapist, and clinically meaningful increases from baseline of COPM and
      GAS scores were recorded. Being physically active at moderate-vigorous levels
      varied between less than 30 and more than 240 minutes/day, and the median for the
      whole group was 84 minutes/day at baseline and 106 minutes/day at 8 months.
      Conclusions: The intervention PAP seems to be feasible and effective for children
      with CP, involving both every day and organised physical activities to promote an
      active lifestyle through increased participation, motivation, and engagement in
      physical activities. Further research of PAP is needed, preferably in a long term
      randomised controlled trial and including health economic analysis to show costs
      and benefits. Trial Registration: ISRCTN76366356, retrospectively registered.

PMID- 29340208
TI  - Are they publishing? A descriptive cross-sectional profile and bibliometric
      analysis of the journal publication productivity of Italian physiotherapists.
AB  - Background: In a clinical science-based profession such as physiotherapy,
      research is mandatory to update knowledge and to provide cost-effective, high
      quality treatments. This study aimed to provide point prevalence of Italian
      physiotherapists who are academics, holding a PhD degree, or being authors of
      scientific papers. The scientific journal productivity of physiotherapists was
      also thoroughly analyzed. Methods: A descriptive cross-sectional study was
      carried out on all Italian physiotherapists. Academics, postdoctoral research
      fellows, and PhD graduates were identified by searching the Italian Ministry of
      Education, University and Research (MIUR), Italian Society of Physiotherapy, and
      university websites. Then, authors of articles indexed in Scopus were searched.
      The following data were extracted: type of affiliation, authorship order, H
      index, number of publications and citations, name of journals, year of
      publication, and journal's Impact Factor. Results: The prevalence of academics,
      physiotherapists holding a PhD, or being author was 0.01%, 0.05%, and 0.56%,
      respectively. We identified 1083 papers co-authored by Italian physiotherapists,
      and their number has progressively increased over the years (p < 0.001). There
      was a significant difference between researchers and clinicians in both
      publication productivity (p < 0.01), citations (p < 0.01), and H-Index (p =
      0.05). Articles were published in 359 different journals, receiving a total of
      13,373 citations. Conclusions: Despite the low prevalence of faculty members and
      the reduced availability of PhD programs in Italy (forcing some students to study
      abroad), the quantity and quality of journal productivity is growing fast, and an
      increasing number of physiotherapists are involved in research activities.

PMID- 29340210
TI  - TreeTime: Maximum-likelihood phylodynamic analysis.
AB  - Mutations that accumulate in the genome of cells or viruses can be used to infer
      their evolutionary history. In the case of rapidly evolving organisms, genomes
      can reveal their detailed spatiotemporal spread. Such phylodynamic analyses are
      particularly useful to understand the epidemiology of rapidly evolving viral
      pathogens. As the number of genome sequences available for different pathogens
      has increased dramatically over the last years, phylodynamic analysis with
      traditional methods becomes challenging as these methods scale poorly with
      growing datasets. Here, we present TreeTime, a Python-based framework for
      phylodynamic analysis using an approximate Maximum Likelihood approach. TreeTime
      can estimate ancestral states, infer evolution models, reroot trees to maximize
      temporal signals, estimate molecular clock phylogenies and population size
      histories. The runtime of TreeTime scales linearly with dataset size.

PMID- 29340211
TI  - Differences in adaptive dynamics determine the success of virus variants that
      propagate together.
AB  - Virus fitness is a complex parameter that results from the interaction of virus
      specific characters (e.g. intracellular growth rate, adsorption rate, virion
      extracellular stability, and tolerance to mutations) with others that depend on
      the underlying fitness landscape and the internal structure of the whole
      population. Individual mutants usually have lower fitness values than the complex
      population from which they come from. When they are propagated and allowed to
      attain large population sizes for a sufficiently long time, they approach
      mutation-selection equilibrium with the concomitant fitness gains. The
      optimization process follows dynamics that vary among viruses, likely due to
      differences in any of the parameters that determine fitness values. As a
      consequence, when different mutants spread together, the number of generations
      experienced by each of them prior to co-propagation may determine its particular
      fate. In this work we attempt a clarification of the effect of different levels
      of population diversity in the outcome of competition dynamics. To this end, we
      analyze the behavior of two mutants of the RNA bacteriophage Qbeta that co
      propagate with the wild-type virus. When both competitor viruses are clonal, the
      mutants rapidly outcompete the wild type. However, the outcome in competitions
      performed with partially optimized virus populations depends on the distance of
      the competitors to their clonal origin. We also implement a theoretical
      population dynamics model that describes the evolution of a heterogeneous
      population of individuals, each characterized by a fitness value, subjected to
      subsequent cycles of replication and mutation. The experimental results are
      explained in the framework of our theoretical model under two non-excluding,
      likely complementary assumptions: (1) The relative advantage of both competitors
      changes as populations approach mutation-selection equilibrium, as a consequence
      of differences in their growth rates and (2) one of the competitors is more
      robust to mutations than the other. The main conclusion is that the nearness of
      an RNA virus population to mutation-selection equilibrium is a key factor
      determining the fate of particular mutants arising during replication.

PMID- 29340209
TI  - Discovery of Culex pipiens associated tunisia virus: a new ssRNA(+) virus
      representing a new insect associated virus family.
AB  - In the global context of arboviral emergence, deep sequencing unlocks the
      discovery of new mosquito-borne viruses. Mosquitoes of the species Culex pipiens,
      C. torrentium, and C. hortensis were sampled from 22 locations worldwide for
      transcriptomic analyses. A virus discovery pipeline was used to analyze the
      dataset of 0.7 billion reads comprising 22 individual transcriptomes. Two closely
      related 6.8 kb viral genomes were identified in C. pipiens and named as Culex
      pipiens associated tunisia virus (CpATV) strains Ayed and Jedaida. The CpATV
      genome contained four ORFs. ORF1 possessed helicase and RNA-dependent RNA
      polymerase (RdRp) domains related to new viral sequences recently found mainly in
      dipterans. ORF2 and 4 contained a capsid protein domain showing strong homology
      with Virgaviridae plant viruses. ORF3 displayed similarities with eukaryotic
      Rhoptry domain and a merozoite surface protein (MSP7) domain only found in
      mosquito-transmitted Plasmodium, suggesting possible interactions between CpATV
      and vertebrate cells. Estimation of a strong purifying selection exerted on each
      ORFs and the presence of a polymorphism maintained in the coding region of ORF3
      suggested that both CpATV sequences are genuine functional viruses. CpATV is part
      of an entirely new and highly diversified group of viruses recently found in
      insects, and that bears the genomic hallmarks of a new viral family.

PMID- 29340212
TI  - 40 Years without Smallpox.
AB  - The last case of natural smallpox was recorded in October, 1977. It took humanity
      almost 20 years to achieve that feat after the World Health Organization had
      approved the global smallpox eradication program. Vaccination against smallpox
      was abolished, and, during the past 40 years, the human population has managed to
      lose immunity not only to smallpox, but to other zoonotic orthopoxvirus
      infections as well. As a result, multiple outbreaks of orthopoxvirus infections
      in humans in several continents have been reported over the past decades. The
      threat of smallpox reemergence as a result of evolutionary transformations of
      these zoonotic orthopoxviruses exists. Modern techniques for the diagnostics,
      prevention, and therapy of smallpox and other orthopoxvirus infections are being
      developed today.

PMID- 29340213
TI  - Non-Coding RNAs As Transcriptional Regulators In Eukaryotes.
AB  - Non-coding RNAs up to 1,000 nucleotides in length are widespread in eukaryotes
      and fulfil various regulatory functions, in particular during chromatin
      remodeling and cell proliferation. These RNAs are not translated into proteins:
      thus, they are non-coding RNAs (ncRNAs). The present review describes the
      eukaryotic ncRNAs involved in transcription regulation, first and foremost,
      targeting RNA polymerase II (RNAP II) and/or its major proteinaceous
      transcription factors. The current state of knowledge concerning the regulatory
      functions of SRA and TAR RNA, 7SK and U1 snRNA, GAS5 and DHFR RNA is summarized
      herein. Special attention is given to murine B1 and B2 RNAs and human Alu RNA,
      due to their ability to bind the active site of RNAP II. Discovery of bacterial
      analogs of the eukaryotic small ncRNAs involved in transcription regulation, such
      as 6S RNAs, suggests that they possess a common evolutionary origin.

PMID- 29340214
TI  - The Contribution of Ribosomal Protein S1 to the Structure and Function of Qbeta
      Replicase.
AB  - The high resolution crystal structure of bacterial ribosome was determined more
      than 10 years ago; however, it contains no information on the structure of the
      largest ribosomal protein, S1. This unusual protein comprises six flexibly linked
      domains; therefore, it lacks a fixed structure and this prevents the formation of
      crystals. Besides being a component of the ribosome, protein S1 also serves as
      one of the four subunits of Qbeta replicase, the RNA-directed RNA polymerase of
      bacteriophage Qbeta. In each case, the role of this RNA-binding protein has been
      thought to consist in holding the template close to the active site of the
      enzyme. In recent years, a breakthrough was made in studies of protein S1 within
      Qbeta replicase. This includes the discovery of its paradoxical ability to
      displace RNA from the replicase complex and determining the crystal structure of
      its fragment capable of performing this function. The new findings call for a re
      examination of the contribution of protein S1 to the structure and function of
      the ribosome.

PMID- 29340215
TI  - Genome Stability Maintenance in Naked Mole-Rat.
AB  - The naked mole-rat (Heterocephalus glaber) is one of the most promising models
      used to study genome maintenance systems, including the effective repair of
      damage to DNA. The naked mole-rat is the longest lived rodent species, which is
      extraordinarily resistant to cancer and has a number of other unique phenotypic
      traits. For at least 80% of its lifespan, this animal shows no signs of aging or
      any increased likelihood of death and retains the ability to reproduce. The naked
      mole-rat draws the heightened attention of researchers who study the molecular
      basis of lengthy lifespan and cancer resistance. Despite the fact that the naked
      mole-rat lives under genotoxic stress conditions (oxidative, etc.), the main
      characteristics of its genome and proteome are a high stability and effective
      functioning. Replicative senescence in the somatic cells of naked mole-rats is
      missing, while an additional p53/pRb-dependent mechanism of early contact
      inhibition has been revealed in its fibroblasts, which controls cell
      proliferation and its mechanism of arf-dependent aging. The unique traits of
      phenotypic and molecular adaptations found in the naked mole-rat speak to a high
      stability and effective functioning of the molecular machinery that counteract
      damage accumulation in its genome. This review analyzes existing results in the
      study of the molecular basis of longevity and high cancer resistance in naked
      mole-rats.

PMID- 29340217
TI  - Translational Cross-Activation of the Encapsidated RNA of Potexviruses.
AB  - We had shown the genomic RNA of potexviruses potato virus X and the alternanthera
      mosaic virus to be inaccessible in vitro to ribosomes while in intact virion
      form, but the RNAs can be translationally activated following the binding of
      movement protein 1 (MP1) to virus particles. Here, we present the results of the
      follow-up study targeting two more potexvirus species - the Narcissus mosaic
      virus and the Potato aucuba mosaic virus. We found encapsidated potexviral RNA to
      share common translational features in vitro and the MP1 to be potent over
      homological virions of its "own" species and over heterological virions of other
      species, as well exhibiting selective specificity. Reciprocal cross-activation is
      observed among viral species phylogenetically either close or distant. There is
      direct evidence that MP1 binding to the end of the virion is necessary, but not
      sufficient, for translational activation of encapsidated RNA.

PMID- 29340218
TI  - Synthesis and Characterization of Hybrid Core-Shell Fe3O4/SiO2 Nanoparticles for
      Biomedical Applications.
AB  - The creation of markers that provide both visual and quantitative information is
      of considerable importance for the mapping of tissue macrophages and other cells.
      We synthesized magnetic and magneto-fluorescent nanomarkers for the labeling of
      cells which can be detected with high sensitivity by the magnetic particle
      quantification (MPQ) technique. For stabilization under physiological conditions,
      the markers were coated with a dense silica shell. In this case, the size and
      zeta-potential of nanoparticles were controlled by a modified Stober reaction.
      Also, we developed a novel facile two-step synthesis of carboxylic acid
      functionalized magnetic SiO2 nanoparticles, with a carboxyl polymer shell forming
      on the nanoparticles before the initiation of the Stober reaction. We extensively
      characterized the nanomarkers by transmission electron microscopy, electron
      microdiffraction, and dynamic and electrophoretic light scattering. We also
      studied the nanoparticle cellular uptake by various eukaryotic cell lines.

PMID- 29340216
TI  - Super-Resolution Microscopy in Studying the Structure and Function of the Cell
      Nucleus.
AB  - In recent decades, novel microscopic methods commonly referred to as super-
      resolution microscopy have been developed. These methods enable the visualization
      of a cell with a resolution of up to 10 nm. The application of these methods is
      of great interest in studying the structure and function of the cell nucleus. The
      review describes the main achievements in this field.

PMID- 29340219
TI  - A Novel Hybrid Promoter ARE-hTERT for Cancer Gene Therapy.
AB  - describe a novel hybrid tumor-specific promoter, ARE-hTERT, composed of the human
      TERT gene promoter (hTERT) and the antioxidant response element (ARE) from the
      human GCLM gene promoter. The hybrid promoter retains the tumor specificity of
      the basal hTERT promoter but is characterized by an enhanced transcriptional
      activity in cancer cells with abnormal activation of the Nrf2 transcription
      factor and upon induction of oxidative stress. In the in vitro enzyme-prodrug
      cancer gene therapy scheme, ARE-hTERT promoter-driven expression of CD : UPRT
      (yeast cytosine deaminase : uracil phosphoribosyltransferase) chimeric protein
      induced a more pronounced death of cancer cells either upon treatment with 5
      fluorouracil (5FC) alone or when 5FC was combined with chemotherapeutic drugs as
      compared to the hTERT promoter. The developed hybrid promoter can be considered a
      better alternative to the hTERT promoter in cancer gene therapy schemes.

PMID- 29340220
TI  - Multilocus Analysis of Genetic Susceptibility to Myocardial Infarction in
      Russians: Replication Study.
AB  - In search of genetic markers of myocardial infarction (MI) risk, which have
      prognostic significance for Russians, we performed a replication study of MI
      association with genetic variants of PCSK9 (rs562556), APOE (epsilon
      polymorphism, rs7412 and rs429358), LPL (rs320), MTHFR (rs1801133), eNOS
      (rs2070744), and the 9p21 region (rs1333049) in 405 patients with MI and 198
      controls. Significant MI association was observed with variants of the lipid
      metabolism genes (PCSK9, APOE and LPL), and of eNOS. The SNPs in the MTHFR gene
      and the 9p21 region were not significantly associated with MI one by one but were
      included in several different MI-associated allelic combinations identified by
      multilocus analysis. Since we have not revealed nonlinear epistatic interactions
      between the components of the identified combinations, we postulate that the
      cumulative effect of genes that form a combination arises from the summation of
      their small independent contributions. The prognostic significance of the
      additive composite model built from the PCSK9, APOE, LPL, and eNOS genes as
      genetic markers was assessed using ROC analysis. After we included these markers
      in the previously published composite model of individual genetic risk of MI, the
      prognostic efficacy in our sample reached AUC = 0.676. However, the results
      obtained in this study certainly need to be replicated in an independent sample
      of Russians.

PMID- 29340221
TI  - Recombinant Antibodies to the Ebola Virus Glycoprotein.
AB  - Currently, there are no approved therapies for targeted prevention and treatment
      of Ebola hemorrhagic fever. In the present work, we describe the development of a
      eukaryotic expression system for the production of three full-length chimeric
      antibodies (IgG1-kappa isotypes) GPE118, GPE325, and GPE534 to the recombinant
      glycoprotein of the Ebola virus (EBOV GP), which is a key factor in the
      pathogenicity of the disease. The immunochemical properties of the obtained
      antibodies were studied by immunoblotting and indirect, direct, and competitive
      ELISA using the recombinant EBOV proteins rGPdTM, NP, and VP40. The authenticity
      of the antibodies and the absence of cross-specificity with respect to the
      structural proteins NP and VP40 of the Ebola virus were proved. The epitope
      specificity of the resulting recombinant antibodies was studied using commercial
      neutralizing antibodies against the viral glycoprotein. The recombinant
      antibodies GPE118, GPE325, and GPE534 were shown to recognize glycoprotein
      epitopes that coincide or overlap with the epitopes of three well-studied
      neutralizing anti-Ebola virus antibodies.

PMID- 29340222
TI  - Direct Molecular Fishing of New Protein Partners for Human Thromboxane Synthase.
AB  - Thromboxane synthase (TBXAS1) catalyzes the isomerization reaction of
      prostaglandin H2 producing thromboxane A2, the autocrine and paracrine factor in
      many cell types. A high activity and metastability by these arachidonic acid
      derivatives suggests the existence of supramolecular structures that are involved
      in the regulation of the biosynthesis and directed translocation of thromboxane
      to the receptor. The objective of this study was to identify TBXAS1 protein
      partners from human liver tissue lysate using a complex approach based on the
      direct molecular fishing technique, LC-MS/MS protein identification, and protein
      protein interaction validation by surface plasmon resonance (SPR). As a result,
      12 potential TBXAS1 protein partners were identified, including the components
      regulating cytoskeleton organization (BBIP1 and ANKMY1), components of the
      coagulation cascade of human blood (SERPINA1, SERPINA3, APOH, FGA, and FN1), and
      the enzyme involved in the metabolism of xenobiotics and endogenous bioregulators
      (CYP2E1). SPR validation on the Biacore 3000 biosensor confirmed the
      effectiveness of the interaction between CYP2E1 (the enzyme that converts
      prostaglandin H2 to 12-HHT/thromboxane A2 proantagonist) and TBXAS1 (Kd = (4.3 +/
      0.4) * 10-7 M). Importantly, the TBXAS1*CYP2E1 complex formation increases
      fivefold in the presence of isatin (indole-2,3-dione, a low-molecular nonpeptide
      endogenous bioregulator, a product of CYP2E1). These results suggest that the
      interaction between these hemoproteins is important in the regulation of the
      biosynthesis of eicosanoids.

PMID- 29340223
TI  - YABBY3-Orthologous Genes in Wild Tomato Species: Structure, Variability, and
      Expression.
AB  - Evolution of the genes encoding YABBY transcription factors is believed to be one
      of the key reasons for flat leaf emergence from the radially symmetrical stem and
      gynoecium diversity. YABBY genes determine the identity of the abaxial surface of
      all aboveground lateral organs in seed plants. In the present study, complete
      sequences of YABBY3-orthologous genes were identified and characterized in 13
      accessions of cultivated and wild tomato species with diverse morphophysiology of
      leaves, flowers, and fruits. The obtained gene sequences showed high homology (95
      99%) and an identical exon-intron structure with the known S. lycopersicum YABBY3
      gene, and they contained sequences that encode the conserved HMG-like YABBY and
      Cys2Cys2-zinc-finger domains. In total, in the analyzed YABBY3 genes, 317
      variable sites were found, wherein 8 of 24 exon-specific SNPs were nonsynonymous.
      In the vegetative and reproductive organs of red-fruited and green-fruited tomato
      species, YABBY3 gene expression was similar to that in S. pimpinellifolium
      described earlier, but it demonstrated interspecies differences at the leaf-, bud
      and flower-specific expression levels.

PMID- 29340224
TI  - CaMKII Is Involved in the Choline-Induced Downregulation of Acetylcholine Release
      in Mouse Motor Synapses.
AB  - We investigated the involvement of calcium-dependent enzymes, protein kinase C
      (PKC) and calcium-calmodulin-dependent protein kinase II (CaMKII), in the
      signaling pathway triggered by the activation of presynaptic alpha7-type
      nicotinic acetylcholine receptors by exogenous choline, leading to downregulation
      of the evoked acetylcholine (ACh) release in mouse motor synapses. Blockade of
      PKC with chelerythrine neither changed the evoked release of ACh by itself nor
      prevented the inhibitory effect of choline. The CaMKII blocker KN-62 did not
      affect synaptic activity but fully prevented the choline-induced downregulation
      of ACh release.

PMID- 29340225
TI  - Effects of Calcium on Drinking Fluorosis-induced Hippocampal Synaptic Plasticity
      Impairment in the Offspring of Rats.
AB  - Objective: This study investigated the effects of calcium on fluorosis-induced
      impairment in learning and memory of offspring rats. Methods Seventy-five newly
      weaned female Sprague-Dawley (SD) rats were randomly divided into five groups as
      follows: Control group (Control) drank tap water, and ate the normal diet
      (calcium content of 0.79%); fluoride group (F) drank 100 mg/L NaF solution, and
      ate the normal diet; low calcium group (LCa) drank tap water, and ate the low
      calcium diet (calcium content of 0.063%); low calcium fluoride group (F+LCa)
      drank 100 mg/L NaF solution, and ate the low calcium diet; high calcium fluoride
      group (F+HCa) drank 100 mg/L NaF solution, and ate the high calcium diet (calcium
      content of 7%). After exposing rats to fluoride for three months, male and female
      rats were mated and 14 and 28 days old offspring were obtained as experimental
      subjects. Examinations determined the submicroscopic parameters of the synaptic
      interface and expression levels of specific proteins: doublecortin (DCX) and
      synaptophysin (p38). Results: (1) High fluorosis significantly reduced synapse
      density, length of synaptic active zone, thickness of postsynaptic density, and
      led to abnormal changes in the structural parameter of synaptic gap width, which
      was significantly reduced or increased. High dietary calcium significantly
      reversed the abnormal changes in structural parameters, and low calcium
      aggravated these variations. (2) Dietary calcium resulted in nonsignificant
      effect on expression levels of DCX and p38. Conclusion: The results suggested
      that dietary calcium significantly affected hippocampal synaptic plasticity of
      offspring of mothers exposed to water fluorosis, but its molecular mechanism may
      not be related to the expression of DCX and p38 in the brain. The findings also
      demonstrate the important effects of maternal exposure to water fluorosis on
      offspring brain functions before water improvement.

PMID- 29340226
TI  - Depression is Associated with CRP SNPs in Patients with Family History.
AB  - Objective: The pathogenesis of depression is not fully understood, but studies
      have suggested that higher circulating levels of C reactive protein (CRP) might
      relate to depression occurrence. However, due to the highly variability of
      individual patients' conditions, the results to date are inconsistent.
      Considering Single nucleotide polymorphisms (SNPs) of CRP gene have also been
      suggested to predict plasma CRP levels. In the present study, we hypothesize that
      inherited CRP allelic variations may co-vary with depressive symptomatology.
      Methods: We recruited patients with a diagnosis of depression, with or without
      family depression history. We then detected serum CRP levels, as well as genome
      CRP SNPs from participants of this project. Results: We found a significantly
      higher circulating CRP levels in patients with a positive family history.
      Furthermore, we also identified certain inherited CRP SNPs (A allele in rs1417938
      and C allele in rs1205) which could up-regulate serum CRP levels and thus be
      associated with depression occurrence. Conclusion: Our findings raise new
      evidence for the relationship between circulating CRP level and depression
      occurrence.

PMID- 29340227
TI  - Keyhole Surgery of Pineal Area Tumors - Personal Experience in 22 Patients.
AB  - Background: Pineal area tumors are challenging for surgery due to their location.
      However, the removal of the lesion is critical for further treatment and survival
      of the patients. Material and methods: 22 patients with pineal area tumors were
      surgically treated via keyhole medial suboccipital craniotomy and supracerebellar
      midline approach All the patients were operated in the sitting position with the
      use of operating microscope and microsurgical technique. Results: All patients
      survived surgery in a perfect condition, and no one patient worsened after
      surgery. No complications due to the sitting position were noted. Conclusions:
      Surgical removal of pineal area tumors via small suboccipital craniotomy is safe
      and with the use of microsurgical techniques the results of surgical treatment
      are excellent. The sitting position of the patients gives a better view to the
      surgeon. We did not observe any intraoperational complications due to the sitting
      position.

PMID- 29340228
TI  - A new small-bodied ornithopod (Dinosauria, Ornithischia) from a deep, high-energy
      Early Cretaceous river of the Australian-Antarctic rift system.
AB  - A new small-bodied ornithopod dinosaur, Diluvicursor pickeringi, gen. et sp.
      nov., is named from the lower Albian of the Eumeralla Formation in southeastern
      Australia and helps shed new light on the anatomy and diversity of Gondwanan
      ornithopods. Comprising an almost complete tail and partial lower right hindlimb,
      the holotype (NMV P221080) was deposited as a carcass or body-part in a log
      filled scour near the base of a deep, high-energy river that incised a faunally
      rich, substantially forested riverine floodplain within the Australian-Antarctic
      rift graben. The deposit is termed the 'Eric the Red West Sandstone.' The
      holotype, interpreted as an older juvenile ~1.2 m in total length, appears to
      have endured antemortem trauma to the pes. A referred, isolated posterior caudal
      vertebra (NMV P229456) from the holotype locality, suggests D. pickeringi grew to
      at least 2.3 m in length. D. pickeringi is characterised by 10 potential
      autapomorphies, among which dorsoventrally low neural arches and transversely
      broad caudal ribs on the anterior-most caudal vertebrae are a visually defining
      combination of features. These features suggest D. pickeringi had robust anterior
      caudal musculature and strong locomotor abilities. Another isolated anterior
      caudal vertebra (NMV P228342) from the same deposit, suggests that the fossil
      assemblage hosts at least two ornithopod taxa. D. pickeringi and two
      stratigraphically younger, indeterminate Eumeralla Formation ornithopods from
      Dinosaur Cove, NMV P185992/P185993 and NMV P186047, are closely related. However,
      the tail of D. pickeringi is far shorter than that of NMV P185992/P185993 and its
      pes more robust than that of NMV P186047. Preliminary cladistic analysis,
      utilising three existing datasets, failed to resolve D. pickeringi beyond a large
      polytomy of Ornithopoda. However, qualitative assessment of shared anatomical
      features suggest that the Eumeralla Formation ornithopods, South American
      Anabisetia saldiviai and Gasparinisaura cincosaltensis, Afro-Laurasian
      dryosaurids and possibly Antarctic Morrosaurus antarcticus share a close
      phylogenetic progenitor. Future phylogenetic analysis with improved data on
      Australian ornithopods will help to test these suggested affinities.

PMID- 29340229
TI  - Acquired melanocytic naevus phenotypes and MC1R genotypes in Han Chinese: a cross
      sectional study.
AB  - Background: Early detection and treatment are the most important elements in
      reducing the incidence of melanoma deaths. Acquired melanocytic naevi (AMN) are
      well-known precursors of melanoma but most of our knowledge on the clinico
      dermoscopic phenotypes of AMN is based on studies in European-background
      populations, particularly American and Australian populations. There has been
      little research in Chinese Han populations on clinico-dermoscopic variability of
      naevi or how naevi are affected by melanoma-linked variants of the melanocortin 1
      receptor (MC1R) gene. Methods: Clinical and dermoscopic features of 448 AMN in
      115 patients from the Han ethnic group in mainland China were described. Germline
      polymorphisms in MC1R were determined for 98 of these patients. Results: AMN were
      predominantly found on the head and neck. Dermoscopic patterns observed were
      nonspecific, reticular, globular, and parallel furrow, with most AMN having a
      nonspecific pattern. There were no associations between MC1R polymorphisms and
      clinical or dermoscopic features of AMN. Discussion: Our results provide evidence
      that AMN in the Han population in China have similar dermoscopic patterns to
      those in European populations, but are present in much lower numbers. As there
      were no associations between clinical or dermoscopic features of AMN and MC1R
      polymorphisms, further studies should focus on candidate gene associations with
      AMN features and the risk of melanoma, with larger sample sizes and comparisons
      to AMN in other populations.

PMID- 29340230
TI  - Arbutin increases Caenorhabditis elegans longevity and stress resistance.
AB  - Arbutin (p-hydroxyphenyl-beta-D-glucopyranoside), a well-known tyrosinase
      inhibitor, has been widely used as a cosmetic whitening agent. Although its
      natural role is to scavenge free radicals within cells, it has also exhibited
      useful activities for the treatment of diuresis, bacterial infections and cancer,
      as well as anti-inflammatory and anti-tussive activities. Because function of
      free radical scavenging is also related to antioxidant and the effects of arbutin
      on longevity and stress resistance in animals have not yet been confirmed, here
      the effects of arbutin on Caenorhabditis elegans were investigated. The results
      demonstrated that optimal concentrations of arbutin could extend lifespan and
      enhance resistance to oxidative stress. The underlying molecular mechanism for
      these effects involves decreased levels of reactive oxygen species (ROS),
      improvement of daf-16 nuclear localization, and up-regulated expression of daf-16
      and its downstream targets, including sod-3 and hsp16.2. In this work the roles
      of arbutin in lifespan and health are studied and the results support that
      arbutin is an antioxidant for maintaining overall health.

PMID- 29340232
TI  - The effects of arbuscular mycorrhizal fungi and root interaction on the
      competition between Trifolium repens and Lolium perenne.
AB  - Understanding the factors that alter competitive interactions and coexistence
      between plants is a key issue in ecological research. A pot experiment was
      conducted to test the effects of root interaction and arbuscular mycorrhizal
      fungi (AMF) inoculation on the interspecies competition between Trifolium repens
      and Lolium perenne under different proportions of mixed sowing by the combination
      treatment of two levels of AMF inoculation (inoculation and non-inoculation) and
      two levels of root interaction (root interaction and non-root interaction).
      Overall, the aboveground and belowground biomass of T. repens and L. perenne were
      not altered by AMF inoculation across planting ratios, probably because the
      fertile soil reduced the positive effect of AMF on plant growth. Both inter- and
      intraspecies root interaction significantly decreased the aboveground biomass of
      T. repens, but tended to increase the aboveground biomass of L. perenne across
      planting ratios, and thus peaked at the 4:4 polyculture. These results showed
      that T. repens competed poorly with L. perenne because of inter and intraspecies
      root interaction. Our results indicate that interspecies root interaction
      regulates the competitive ability of grass L. perenne and legume T. repens in
      mixtures and further makes great contribution for overyielding. Furthermore, AMF
      may not be involved in plant-plant interaction in fertile condition.

PMID- 29340231
TI  - ksrMKL: a novel method for identification of kinase-substrate relationships using
      multiple kernel learning.
AB  - Phosphorylation exerts a crucial role in multiple biological cellular processes
      which is catalyzed by protein kinases and closely related to many diseases.
      Identification of kinase-substrate relationships is important for understanding
      phosphorylation and provides a fundamental basis for further disease-related
      research and drug design. In this study, we develop a novel computational method
      to identify kinase-substrate relationships based on multiple kernel learning. The
      comparative analysis is based on a 10-fold cross-validation process and the
      dataset collected from the Phospho.ELM database. The results show that ksrMKL is
      greatly improved in various measures when compared with the single kernel support
      vector machine. Furthermore, with an independent test dataset extracted from the
      PhosphoSitePlus database, we compare ksrMKL with two existing kinase-substrate
      relationship prediction tools, namely iGPS and PKIS. The experimental results
      show that ksrMKL has better prediction performance than these existing tools.

PMID- 29340233
TI  - Crustacean amphipods from marsh ponds: a nutritious feed resource with potential
      for application in Integrated Multi-Trophic Aquaculture.
AB  - Coastal protection, nutrient cycling, erosion control, water purification, and
      carbon sequestration are ecosystem services provided by salt marshes.
      Additionally, salt ponds offer coastal breeding and a nursery habitat for fishes
      and they provide abundant invertebrates, such as amphipods, which are potentially
      useful as a resource in aquaculture. Fishmeal and fish oil are necessary food
      resources to support aquaculture of carnivorous species due to their omega-3 long
      chain polyunsaturated fatty acids (n-3 LC-PUFA). Currently, aquaculture depends
      on limited fisheries and feed with elevated n-3 LC-PUFA levels, but the
      development of more sustainable food sources is necessary. Amphipods appear to be
      a potential high quality alternative feed resource for aquaculture. Hence, a
      nutritional study was carried out for several main amphipod species-Microdeutopus
      gryllotalpa, Monocorophium acherusicum, Gammarus insensibilis, Melita palmata and
      Cymadusa filosa-in terrestrial ponds in the South of Spain. These species showed
      high protein content (up to 40%), high n-3 PUFA and phospholipid levels, and high
      levels of phophatidylcholine (PC), phosphatidylethanolamine (PE) and
      triacylglycerols (TAG), the latter being significantly high for M. acherusicum.
      M. gryllotalpa and M. acherusicum showed the highest proportion of lipids (19.15%
      and 18.35%, respectively). Isoleucine, glycine and alanine were the dominant
      amino acids in all species. In addition, amphipods collected from ponds showed
      low levels of heavy metals. Furthermore, the biochemical profiles of the five
      species of amphipods have been compared with other studied alternative prey.
      Therefore, pond amphipods are good candidates to be used as feed, and are
      proposed as a new sustainable economic resource to be used in aquaculture. G.
      insensibilis may be the best for intensive culture as an alternative feed
      resource because it shows: (1) adequate n-3 PUFA and PL composition; (2) high
      levels of glycine, alanine, tyrosine, isoleucine and lysine; (3) high natural
      densities; (4) large body size (>=1 cm), and (5) high concentration of calcium.
      Moreover, a combined culture of amphipods and fishes in these marsh ponds seems a
      promising and environmentally sustainable way to develop Integrate Multi-Trophic
      Aquaculture (IMTA) in these ecosystems.

PMID- 29340234
TI  - Achilles heel of a powerful invader: restrictions on distribution and
      disappearance of feral pigs from a protected area in Northern Pantanal, Western
      Brazil.
AB  - This paper focuses on a rare case of natural disappearance of feral pigs (Sus
      scrofa) in an extensive area without using traditional methods of eradication
      programs. The study was conducted both in the Private Reserve of Natural Heritage
      (PRNH) Sesc Pantanal and in an adjacent traditional private cattle ranch. In
      1998, feral pigs were abundant and widely distributed in the PRNH. However, the
      feral pigs gradually disappeared from the area and currently, the absence of pigs
      in the PRNH contrasts with the adjacent cattle ranch where the species is
      abundant. To understand the current distribution of the species in the region we
      partitioned the effects of variation of feral pigs' presence considering the
      habitat structure (local), landscape composition and the occurrence of potential
      predators. Additionally, we modeled the distributions of the species in Northern
      Pantanal, projecting into the past using the classes of vegetation cover before
      the PRNH implementation (year 1988). Our results show areas with more suitability
      for feral pigs in regions where the landscape is dominated by pastures and
      permeated by patches of Seasonal Dry Forest. The species tends to avoid
      predominantly forested areas. Additionally, we recorded that the environmental
      suitability decreases exponentially as the distance from water bodies increases.
      The disappearance of feral pigs in the PRNH area seems to be associated with
      changes in the landscape and vegetation structure after the removal of the
      cattle. In the Brazilian Pantanal, the feral pigs' occurrence seems strongly
      conditioned to environmental changes associated to livestock activity.

PMID- 29340235
TI  - Evidence-based design and evaluation of a whole genome sequencing clinical report
      for the reference microbiology laboratory.
AB  - Background: Microbial genome sequencing is now being routinely used in many
      clinical and public health laboratories. Understanding how to report complex
      genomic test results to stakeholders who may have varying familiarity with
      genomics-including clinicians, laboratorians, epidemiologists, and researchers-is
      critical to the successful and sustainable implementation of this new technology;
      however, there are no evidence-based guidelines for designing such a report in
      the pathogen genomics domain. Here, we describe an iterative, human-centered
      approach to creating a report template for communicating tuberculosis (TB)
      genomic test results. Methods: We used Design Study Methodology-a human centered
      approach drawn from the information visualization domain-to redesign an existing
      clinical report. We used expert consults and an online questionnaire to discover
      various stakeholders' needs around the types of data and tasks related to TB that
      they encounter in their daily workflow. We also evaluated their perceptions of
      and familiarity with genomic data, as well as its utility at various clinical
      decision points. These data shaped the design of multiple prototype reports that
      were compared against the existing report through a second online survey, with
      the resulting qualitative and quantitative data informing the final, redesigned,
      report. Results: We recruited 78 participants, 65 of whom were clinicians,
      nurses, laboratorians, researchers, and epidemiologists involved in TB diagnosis,
      treatment, and/or surveillance. Our first survey indicated that participants were
      largely enthusiastic about genomic data, with the majority agreeing on its
      utility for certain TB diagnosis and treatment tasks and many reporting some
      confidence in their ability to interpret this type of data (between 58.8% and
      94.1%, depending on the specific data type). When we compared our four prototype
      reports against the existing design, we found that for the majority (86.7%) of
      design comparisons, participants preferred the alternative prototype designs over
      the existing version, and that both clinicians and non-clinicians expressed
      similar design preferences. Participants showed clearer design preferences when
      asked to compare individual design elements versus entire reports. Both the
      quantitative and qualitative data informed the design of a revised report,
      available online as a LaTeX template. Conclusions: We show how a human-centered
      design approach integrating quantitative and qualitative feedback can be used to
      design an alternative report for representing complex microbial genomic data. We
      suggest experimental and design guidelines to inform future design studies in the
      bioinformatics and microbial genomics domains, and suggest that this type of
      mixed-methods study is important to facilitate the successful translation of
      pathogen genomics in the clinic, not only for clinical reports but also more
      complex bioinformatics data visualization software.

PMID- 29340236
TI  - DNA barcode-based survey of Trichoptera in the Crooked River reveals three new
      species records for British Columbia.
AB  - Anthropogenic pressures on aquatic systems have placed a renewed focus on
      biodiversity of aquatic macroinvertebrates. By combining classical taxonomy and
      DNA barcoding we identified 39 species of caddisflies from the Crooked River, a
      unique and sensitive system in the southernmost arctic watershed in British
      Columbia. Our records include three species never before recorded in British
      Columbia: Lepidostoma togatum (Lepidostomatidae), Ceraclea annulicornis
      (Leptoceridae), and possibly Cheumatopsyche harwoodi (Hydropsychidae). Three
      other specimens may represent new occurrence records and a number of other
      records seem to be substantial observed geographic range expansions within
      British Columbia.

PMID- 29340237
TI  - Using underwater video to evaluate the performance of the Fukui trap as a
      mitigation tool for the invasive European green crab (Carcinus maenas) in
      Newfoundland, Canada.
AB  - The European green crab (Carcinus maenas) is a destructive marine invader that
      was first discovered in Newfoundland waters in 2007 and has since become
      established in nearshore ecosystems on the south and west coast of the island.
      Targeted fishing programs aimed at removing green crabs from invaded Newfoundland
      ecosystems use Fukui traps, but the capture efficiency of these traps has not
      been previously assessed. We assessed Fukui traps using in situ observation with
      underwater video cameras as they actively fished for green crabs. From these
      videos, we recorded the number of green crabs that approached the trap, the
      outcome of each entry attempt (success or failure), and the number of exits from
      the trap. Across eight videos, we observed 1,226 green crab entry attempts, with
      only a 16% rate of success from these attempts. Based on these observations we
      believe there is scope to improve the performance of the Fukui trap through
      modifications in order to achieve a higher catch per unit effort (CPUE),
      maximizing trap usage for mitigation. Ultimately, a more efficient Fukui trap
      will help to control green crab populations in order to preserve the function and
      integrity of ecosystems invaded by the green crab.

PMID- 29340238
TI  - A revised cranial description of Massospondylus carinatus Owen (Dinosauria:
      Sauropodomorpha) based on computed tomographic scans and a review of cranial
      characters for basal Sauropodomorpha.
AB  - Massospondylus carinatus is a basal sauropodomorph dinosaur from the early
      Jurassic Elliot Formation of South Africa. It is one of the best-represented
      fossil dinosaur taxa, known from hundreds of specimens including at least 13
      complete or nearly complete skulls. Surprisingly, the internal cranial anatomy of
      M. carinatus has never been described using computed tomography (CT) methods.
      Using CT scans and 3D digital representations, we digitally reconstruct the bones
      of the facial skeleton, braincase, and palate of a complete, undistorted cranium
      of M. carinatus (BP/1/5241). We describe the anatomical features of the cranial
      bones, and compare them to other closely related sauropodomorph taxa such as
      Plateosaurus erlenbergiensis, Lufengosaurus huenei, Sarahsaurus aurifontanalis
      and Efraasia minor. We identify a suite of character states of the skull and
      braincase for M. carinatus that sets it apart from other taxa, but these remain
      tentative due to the lack of comparative sauropodomorph braincase descriptions in
      the literature. Furthermore, we hypothesize 27 new cranial characters useful for
      determining relationships in non-sauropodan Sauropodomorpha, delete five pre
      existing characters and revise the scores of several existing cranial characters
      to make more explicit homology statements. All the characters that we
      hypothesized or revised are illustrated. Using parsimony as an optimality
      criterion, we then test the relationships of M. carinatus (using BP/1/5241 as a
      specimen-level exemplar) in our revised phylogenetic data matrix.

PMID- 29340239
TI  - FastViromeExplorer: a pipeline for virus and phage identification and abundance
      profiling in metagenomics data.
AB  - With the increase in the availability of metagenomic data generated by next
      generation sequencing, there is an urgent need for fast and accurate tools for
      identifying viruses in host-associated and environmental samples. In this paper,
      we developed a stand-alone pipeline called FastViromeExplorer for the detection
      and abundance quantification of viruses and phages in large metagenomic datasets
      by performing rapid searches of virus and phage sequence databases. Both
      simulated and real data from human microbiome and ocean environmental samples are
      used to validate FastViromeExplorer as a reliable tool to quickly and accurately
      identify viruses and their abundances in large datasets.

PMID- 29340240
TI  - Refining amino acid hydrophobicity for dynamics simulation of membrane proteins.
AB  - Coarse-grained (CG) models have been successful in simulating the chemical
      properties of lipid bilayers, but accurate treatment of membrane proteins and
      lipid-protein molecular interactions remains a challenge. The CgProt force field,
      original developed with the multiscale coarse graining method, is assessed by
      comparing the potentials of mean force for sidechain insertion in a DOPC bilayer
      to results reported for atomistic molecular dynamics simulations. Reassignment of
      select CG sidechain sites from the apolar to polar site type was found to improve
      the attractive interfacial behavior of tyrosine, phenylalanine and asparagine as
      well as charged lysine and arginine residues. The solvation energy at membrane
      depths of 0, 1.3 and 1.7 nm correlates with experimental partition coefficients
      in aqueous mixtures of cyclohexane, octanol and POPC, respectively, for sidechain
      analogs and Wimley-White peptides. These experimental values serve as important
      anchor points in choosing between alternate CG models based on their observed
      permeation profiles, particularly for Arg, Lys and Gln residues where the all
      atom OPLS solvation energy does not agree well with experiment. Available
      partitioning data was also used to reparameterize the representation of the
      peptide backbone, which needed to be made less attractive for the bilayer
      hydrophobic core region. The newly developed force field, CgProt 2.4, correctly
      predicts the global energy minimum in the potentials of mean force for insertion
      of the uncharged membrane-associated peptides LS3 and WALP23. CgProt will find
      application in studies of lipid-protein interactions and the conformational
      properties of diverse membrane protein systems.

PMID- 29340241
TI  - Risk factors for osteoporosis in male patients with chronic obstructive pulmonary
      disease in Taiwan.
AB  - Objective: To investigate the risk factors for osteoporosis in male Taiwanese
      patients with chronic obstructive pulmonary disease (COPD). Methods: This cross
      sectional study evaluated male COPD outpatients and age-matched male subjects at
      a regional teaching hospital. The following data were obtained and analyzed: bone
      mineral density of the lumbar spine and hip on dual-energy X-ray absorptiometry,
      demographic characteristics, questionnaire interview results, pulmonary function
      test results, chest posterior-anterior radiographic findings, and biochemical and
      high-sensitivity C-reactive protein (hs-CRP) levels. Results: Fifty-nine male
      COPD patients and 36 age-matched male subjects were enrolled. COPD patients had
      lower body mass index (BMI) (23.6 +/- 4.1 vs. 25.2 +/- 3.0 kg/m2) and higher
      total prevalence for osteoporosis and osteopenia than controls. Among COPD
      patients, patients with osteoporosis had lower BMI, body weight, waist
      circumference, and triglyceride level but higher hs-CRP level, and tended to have
      lower creatinine level. Binary logistic regression analysis for factors including
      age, BMI, creatinine, hs-CRP, smoking, steroid use, and forced expiratory volume
      in one second (FEV1) revealed that an hs-CRP level >=5 and decreased creatinine
      level were independent risk factors for osteoporosis in COPD patients. Lower BMI
      tended to be associated with osteoporosis development, although it did not reach
      statistical significance, and hs-CRP was associated with COPD severity and
      steroid use history. Conclusion: The total prevalence of osteoporosis and
      osteopenia in male Taiwanese COPD patients is higher than that in age-matched
      male subjects and systemic inflammation is an independent risk factors for
      osteoporosis. Low creatinine level in COPD patients should raise the suspicion of
      sarcopenia and associated increased risk of osteoporosis.

PMID- 29340242
TI  - A diagnostic model for minimal change disease based on biological parameters.
AB  - Background: Minimal change disease (MCD) is a kind of nephrotic syndrome (NS). In
      this study, we aimed to establish a mathematical diagnostic model based on
      biological parameters to classify MCD. Methods: A total of 798 NS patients were
      divided into MCD group and control group. The comparison of biological indicators
      between two groups were performed with t-tests. Logistic regression was used to
      establish the diagnostic model, and the diagnostic value of the model was
      estimated using receiver operating characteristic (ROC) analysis. Results:
      Thirteen indicators including Anti-phospholipase A2 receptor (anti-PLA2R) (P =
      0.000), Total protein (TP) (P = 0.000), Albumin (ALB) (P = 0.000), Direct
      bilirubin (DB) (P = 0.002), Creatinine (Cr) (P = 0.000), Total cholesterol (CH)
      (P = 0.000), Lactate dehydrogenase (LDH) (P = 0.007), High density lipoprotein
      cholesterol (HDL) (P = 0.000), Low density lipoprotein cholesterol (LDL) (P =
      0.000), Thrombin time (TT) (P = 0.000), Plasma fibrinogen (FIB) (P = 0.000),
      Immunoglobulin A (IgA) (P = 0.008) and Complement 3 (C3) (P = 0.019) were
      significantly correlated with MCD. Furthermore, the area under ROC curves of CH,
      HDL, LDL, TT and FIB were more than 0.70. Logistic analysis demonstrated that CH
      and TT were risk factors for MCD. According to the ROC of "CH+TT", the AUC was
      0.827, with the sensitivity of 83.0% and the specificity of 69.8% (P = 0.000).
      Conclusion: The established diagnostic model with CH and TT could be used for
      classified diagnosis of MCD.

PMID- 29340243
TI  - Urban heat island effect on cicada densities in metropolitan Seoul.
AB  - Background: Urban heat island (UHI) effect, the ubiquitous consequence of
      urbanization, is considered to play a major role in population expansion of
      numerous insects. Cryptotympana atrata and Hyalessa fuscata are the most abundant
      cicada species in the Korean Peninsula, where their population densities are
      higher in urban than in rural areas. We predicted a positive relationship between
      the UHI intensities and population densities of these two cicada species in
      metropolitan Seoul. Methods: To test this prediction, enumeration surveys of
      cicada exuviae densities were conducted in 36 localities located within and in
      the vicinity of metropolitan Seoul. Samples were collected in two consecutive
      periods from July to August 2015. The abundance of each species was estimated by
      two resource-weighted densities, one based on the total geographic area, and the
      other on the total number of trees. Multiple linear regression analyses were
      performed to identify factors critical for the prevalence of cicada species in
      the urban habitat. Results: C. atrata and H. fuscata were major constituents of
      cicada species composition collected across all localities. Minimum temperature
      and sampling period were significant factors contributing to the variation in
      densities of both species, whereas other environmental factors related to
      urbanization were not significant. More cicada exuviae were collected in the
      second rather than in the first samplings, which matched the phenological pattern
      of cicadas in metropolitan Seoul. Cicada population densities increased
      measurably with the increase in temperature. Age of residential complex also
      exhibited a significantly positive correlation to H. fuscata densities, but not
      to C. atrata densities. Discussion: Effects of temperature on cicada densities
      have been discerned from other environmental factors, as cicada densities
      increased measurably in tandem with elevated temperature. Several mechanisms may
      contribute to the abundance of cicadas in urban environments, such as higher
      fecundity of females, lower mortality rate of instars, decline in host plant
      quality, and local adaptation of organisms, but none of them were tested in the
      current study. Conclusions: In sum, results of the enumeration surveys of cicada
      exuviae support the hypothesis that the UHI effect underlies the population
      expansion of cicadas in metropolitan Seoul. Nevertheless, the underlying
      mechanisms for this remain untested.

PMID- 29340244
TI  - An exploratory study of adolescent response to fluoxetine using psychological and
      biological predictors.
AB  - Background: Not enough is known about predicting therapeutic response to
      serotonin-specific reuptake inhibitors, and specifically to fluoxetine. This
      exploratory study used psychological and biological markers for (retrospective)
      prediction of treatment-response to fluoxetine in depressed and/or anxious
      adolescents. Methods: Forty-one consecutive adolescent outpatients with a primary
      diagnosis of severe affective and/or anxiety disorders were assessed and treated
      with an open-label 8-week trial of fluoxetine. Type D personality was assessed
      with the 14-item questionnaire, the DS14. In addition, TNFalpha, IL-6, and IL-1b
      were measured pre- and post-treatment. Results: There was an elevation of Type D
      personality in patients, compared to the adolescent population rate. Post
      treatment, 44% of patients were classified as non-responders; the relative risk
      of non-response for Type D personality patients was 2.8. Binary logistic
      regression predicting response vs. non-response showed a contribution of initial
      TNFalpha levels as well as Type D personality to non-response. Conclusions: In
      this exploratory study, the most significant contributor to non-response was Type
      D personality. However, the measurement of Type D was not prospective, and thus
      may be confounded with psychiatric morbidity. The measurement of personality in
      psychiatric settings may contribute to the understanding of treatment response
      and have clinical utility.

PMID- 29340245
TI  - Effects of the visual-feedback-based force platform training with functional
      electric stimulation on the balance and prevention of falls in older adults: a
      randomized controlled trial.
AB  - Background: Force platform training with functional electric stimulation aimed at
      improving balance may be effective in fall prevention for older adults. Aim of
      the study is to evaluate the effects of the visual-feedback-based force platform
      balance training with functional electric stimulation on balance and fall
      prevention in older adults. Methods: A single-centre, unblinded, randomized
      controlled trial was conducted. One hundred and twenty older adults were randomly
      allocated to two groups: the control group (n = 60, one-leg standing balance
      exercise, 12 min/d) or the intervention group (n = 60, force platform training
      with functional electric stimulation, 12 min/d). The training was provided 15
      days a month for 3 months by physical therapists. Medial-lateral and anterior
      posterior maximal range of sway with eyes open and closed, the Berg Balance
      Scale, the Barthel Index, the Falls Efficacy scale-International were assessed at
      baseline and after the 3-month intervention. A fall diary was kept by each
      participant during the 6-month follow-up. Results: On comparing the two groups,
      the intervention group showed significantly decreased (p < 0.01) medial-lateral
      and anterior-posterior maximal range of sway with eyes open and closed. There was
      significantly higher improvement in the Berg Balance Scale (p < 0.05), the
      Barthel Index (p < 0.05) and the Falls Efficacy Scale-International (p < 0.05),
      along with significantly lesser number of injurious fallers (p < 0.05), number of
      fallers (p < 0.05), and fall rates (p < 0.05) during the 6-month follow-up in the
      intervention group. Conclusion: This study showed that the visual feedback-based
      force platform training with functional electric stimulation improved balance and
      prevented falls in older adults.

PMID- 29340246
TI  - Stat-tracks and mediotypes: powerful tools for modern ichnology based on 3D
      models.
AB  - Vertebrate tracks are subject to a wide distribution of morphological types. A
      single trackmaker may be associated with a range of tracks reflecting individual
      pedal anatomy and behavioural kinematics mediated through substrate properties
      which may vary both in space and time. Accordingly, the same trackmaker can leave
      substantially different morphotypes something which must be considered in
      creating ichnotaxa. In modern practice this is often captured by the collection
      of a series of 3D track models. We introduce two concepts to help integrate these
      3D models into ichnological analysis procedures. The mediotype is based on the
      idea of using statistically-generated three-dimensional track models (median or
      mean) of the type specimens to create a composite track to support formal
      recognition of a ichno type. A representative track (mean and/or median) is
      created from a set of individual reference tracks or from multiple examples from
      one or more trackways. In contrast, stat-tracks refer to other digitally
      generated tracks which may explore variance. For example, they are useful in:
      understanding the preservation variability of a given track sample; identifying
      characteristics or unusual track features; or simply as a quantitative comparison
      tool. Both concepts assist in making ichnotaxonomical interpretations and we
      argue that they should become part of the standard procedure when instituting new
      ichnotaxa. As three-dimensional models start to become a standard in publications
      on vertebrate ichnology, the mediotype and stat-track concepts have the potential
      to help guiding a revolution in the study of vertebrate ichnology and
      ichnotaxonomy.

PMID- 29340247
TI  - Weekend effect in upper gastrointestinal bleeding: a systematic review and meta
      analysis.
AB  - Aim: To perform a systematic review and meta-analysis of the weekend effect on
      the mortality of patients with upper gastrointestinal bleeding(UGIB). Methods:
      The review protocol has been registered in the PROSPERO International Prospective
      Register of Systematic Reviews (registration number: CRD42017073313) and was
      written according to the Preferred Reporting Items for Systematic Reviews and
      Meta-Analyses (PRISMA) statement. We conducted a search of the PUBMED, COCHRANE,
      EMBASE and CINAHL databases from inception to August 2017. All observational
      studies comparing mortality between UGIB patients with weekend versus weekday
      admissions were included. Articles that were published only in abstract form or
      not published in a peer-reviewed journal were excluded. The quality of articles
      was assessed using the Newcastle-Ottawa Scale. We pooled results from the
      articles using random-effect models. Heterogeneity was evaluated by the chi
      square-based Q-test and I2 test. To address heterogeneity, we performed
      sensitivity and subgroup analyses. Potential publication bias was assessed via
      funnel plot. Results: Eighteen observational cohort studies involving 1,232,083
      study patients were included. Weekend admission was associated with significantly
      higher 30-day or in-hospital mortality in all studies (OR = 1.12, 95% CI [1.07
      1.17], P < 0.00001). Increased in-hospital mortality was also associated with
      weekend admission (OR = 1.12, 95% CI [1.08-1.17], P < 0.00001). No significant
      difference in in-hospital mortality was observed between patients admitted with
      variceal bleeding during the weekend or on weekdays (OR = 0.99, 95% CI [0.91
      1.08], P = 0.82); however, weekend admission was associated with a 15% increase
      in in-hospital mortality for patients with non-variceal bleeding (OR = 1.15, 95%
      CI [1.09-1.21], P < 0.00001). The time to endoscopy for weekday admission was
      significantly less than that obtained for weekend admission (MD = -2.50, 95% CI [
      4.08--0.92], P = 0.002). Conclusions: The weekend effect is associated with
      increased mortality of UGIB patients, particularly in non-variceal bleeding. The
      timing of endoscopic intervention might be a factor that influences mortality of
      UGIB patients.

PMID- 29340248
TI  - Depth- and range-dependent variation in the performance of aquatic telemetry
      systems: understanding and predicting the susceptibility of acoustic tag-receiver
      pairs to close proximity detection interference.
AB  - Background: Passive acoustic telemetry using coded transmitter tags and
      stationary receivers is a popular method for tracking movements of aquatic
      animals. Understanding the performance of these systems is important in array
      design and in analysis. Close proximity detection interference (CPDI) is a
      condition where receivers fail to reliably detect tag transmissions. CPDI
      generally occurs when the tag and receiver are near one another in acoustically
      reverberant settings. Here we confirm transmission multipaths reflected off the
      environment arriving at a receiver with sufficient delay relative to the direct
      signal cause CPDI. We propose a ray-propagation based model to estimate the
      arrival of energy via multipaths to predict CPDI occurrence, and we show how
      deeper deployments are particularly susceptible. Methods: A series of experiments
      were designed to develop and validate our model. Deep (300 m) and shallow (25 m)
      ranging experiments were conducted using Vemco V13 acoustic tags and VR2-W
      receivers. Probabilistic modeling of hourly detections was used to estimate the
      average distance a tag could be detected. A mechanistic model for predicting the
      arrival time of multipaths was developed using parameters from these experiments
      to calculate the direct and multipath path lengths. This model was retroactively
      applied to the previous ranging experiments to validate CPDI observations. Two
      additional experiments were designed to validate predictions of CPDI with respect
      to combinations of deployment depth and distance. Playback of recorded tags in a
      tank environment was used to confirm multipaths arriving after the receiver's
      blanking interval cause CPDI effects. Results: Analysis of empirical data
      estimated the average maximum detection radius (AMDR), the farthest distance at
      which 95% of tag transmissions went undetected by receivers, was between 840 and
      846 m for the deep ranging experiment across all factor permutations. From these
      results, CPDI was estimated within a 276.5 m radius of the receiver. These
      empirical estimations were consistent with mechanistic model predictions. CPDI
      affected detection at distances closer than 259-326 m from receivers. AMDR
      determined from the shallow ranging experiment was between 278 and 290 m with
      CPDI neither predicted nor observed. Results of validation experiments were
      consistent with mechanistic model predictions. Finally, we were able to predict
      detection/nondetection with 95.7% accuracy using the mechanistic model's
      criterion when simulating transmissions with and without multipaths. Discussion:
      Close proximity detection interference results from combinations of depth and
      distance that produce reflected signals arriving after a receiver's blanking
      interval has ended. Deployment scenarios resulting in CPDI can be predicted with
      the proposed mechanistic model. For deeper deployments, sea-surface reflections
      can produce CPDI conditions, resulting in transmission rejection, regardless of
      the reflective properties of the seafloor.

PMID- 29340249
TI  - A streptomycin resistance marker in H. parasuis based on site-directed mutations
      in rpsL gene to perform unmarked in-frame mutations and to verify natural
      transformation.
AB  - Haemophilus parasuis is a member of the family Pasteurellaceae and a major
      causative agent of Glasser's disease. This bacterium is normally a benign swine
      commensal but may become a deadly pathogen upon penetration into multiple
      tissues, contributing to severe lesions in swine. We have established a
      successive natural transformation-based markerless mutation system in this
      species. However, the two-step mutation system requires screening of natural
      competent cells, and cannot delete genes which regulate natural competence per
      se. In this study, we successfully obtained streptomycin-resistant derivatives
      from H. parasuis wild type strain SC1401 by using ethyl methane sulfonate (EMS,
      CH3SO2OC2H5). Upon sequencing and site-directed mutations, we uncovered that the
      EMS-induced point mutation in rpsL at codon 43rd (AAA -> AGA; K43R) or at 88th
      (AAA -> AGA; K88R) confers a much higher streptomycin resistance than clinical
      isolates. We have applied the streptomycin resistance marker as a positive
      selection marker to perform homologous recombination through conjugation and
      successfully generated a double unmarked in-frame targeted mutant
      1401D88?tfox?arcA. Combined with a natural transformation-based knockout system
      and this genetic technique, multiple deletion mutants or attenuated strains of H.
      parasuis can be easily constructed. Moreover, the mutant genetic marker rpsL and
      streptomycin resistant phenotypes can serve as an effective tool to select
      naturally competent strains, and to verify natural transformation quantitatively.

PMID- 29340250
TI  - Integrated genomic analyses of lung squamous cell carcinoma for identification of
      a possible competitive endogenous RNA network by means of TCGA datasets.
AB  - The etiology of cancer includes aberrant cellular homeostasis where a compromised
      RNA regulatory network is a prominent contributing factor. In particular,
      noncoding RNAs including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs)
      were recently shown to play important roles in the initiation, progression, and
      metastasis of human cancers. Nonetheless, a mechanistic understanding of
      noncoding RNA functions in lung squamous cell carcinoma (LUSC) is lacking. To
      fill this critical gap in knowledge, we obtained mRNA, miRNA, and lncRNA
      expression data on patients with LUSC from the updated Cancer Genome Atlas (TCGA)
      database (2016). We successfully identified 3,366 mRNAs, 79 miRNAs, and 151
      lncRNAs as key contributing factors of a high risk of LUSC. Furthermore, we
      hypothesized that the lncRNA-miRNA-mRNA regulatory axis positively correlates
      with LUSC and constructed a competitive endogenous RNA (ceRNA) network of LUSC by
      targeting interrelations with significantly aberrant expression data between
      miRNA and mRNA or lncRNA. Six ceRNAs (PLAU, miR-31-5p, miR-455-3p, FAM83A-AS1,
      MIR31HG, and MIR99AHG) significantly correlated with survival (P < 0.05).
      Finally, real-time quantitative PCR analysis showed that PLAU is significantly
      upregulated in SK-MES-1 cells compared with 16-BBE-T cells. Taken together, our
      findings represent new knowledge for a better understanding the ceRNA network in
      LUSC biology and pave the way to improved diagnosis and prognosis of LUSC.

PMID- 29340251
TI  - The relationships between exercise and affective states: a naturalistic,
      longitudinal study of recreational runners.
AB  - Background: Although people generally feel more positive and more energetic in
      the aftermath of exercise than before, longitudinal research on how exercise
      relates to within-person fluctuations in affect over the course of everyday life
      is still relatively limited. One constraint on doing such research is the need to
      provide participants with accelerometers to objectively record their exercise,
      and pagers to capture affective reports. Aims: We aimed to develop a methodology
      for studying affect and exercise using only technology that participants already
      possess, namely GPS running watches and smartphones. Using this methodology, we
      aimed to characterize within-individual fluctuations in affective valence and
      arousal in relation to bouts of exercise, and explore possible moderators of
      these fluctuations. Methods: We recruited a sample of 38 recreational runners.
      Participants provided daily affective reports for six weeks using their
      smartphones. Information on their runs was harvested from their own GPS devices
      via an online platform for athletes. Results: Average valence and arousal were
      higher on days when the person had run than on the next day, and higher the day
      after a run than on the days after that. Over the course of the day of a run,
      valence and arousal declined significantly as the time since the run increased.
      Physically fitter participants had more positive valence overall, and this was
      particularly true when they had not run recently. There was some evidence of
      higher-dose (i.e., longer and faster) runs being associated with lower arousal on
      the next and subsequent days. Gender did not moderate associations between
      running and valence or arousal. Discussion: Our study demonstrated the potential
      for studying the associations between affect and exercise in a way that is
      precise, undemanding for participants, and convenient for researchers, using
      technologies that participants already own and use.

PMID- 29340253
TI  - RBiomirGS: an all-in-one miRNA gene set analysis solution featuring target mRNA
      mapping and expression profile integration.
AB  - Background: With the continuous discovery of microRNA's (miRNA) association with
      a wide range of biological and cellular processes, expression profile-based
      functional characterization of such post-transcriptional regulation is crucial
      for revealing its significance behind particular phenotypes. Profound advancement
      in bioinformatics has been made to enable in depth investigation of miRNA's role
      in regulating cellular and molecular events, resulting in a huge quantity of
      software packages covering different aspects of miRNA functional analysis.
      Therefore, an all-in-one software solution is in demand for a comprehensive yet
      highly efficient workflow. Here we present RBiomirGS, an R package for a miRNA
      gene set (GS) analysis. Methods: The package utilizes multiple databases for
      target mRNA mapping, estimates miRNA effect on the target mRNAs through miRNA
      expression profile and conducts a logistic regression-based GS enrichment.
      Additionally, human ortholog Entrez ID conversion functionality is included for
      target mRNAs. Results: By incorporating all the core steps into one package,
      RBiomirGS eliminates the need for switching between different software packages.
      The modular structure of RBiomirGS enables various access points to the analysis,
      with which users can choose the most relevant functionalities for their workflow.
      Conclusions: With RBiomirGS, users are able to assess the functional significance
      of the miRNA expression profile under the corresponding experimental condition by
      minimal input and intervention. Accordingly, RBiomirGS encompasses an all-in-one
      solution for miRNA GS analysis. RBiomirGS is available on GitHub
      (http://github.com/jzhangc/RBiomirGS). More information including instruction and
      examples can be found on website (http://kenstoreylab.com/?page_id=2865).

PMID- 29340252
TI  - Positive selection on human gamete-recognition genes.
AB  - Coevolution of genes that encode interacting proteins expressed on the surfaces
      of sperm and eggs can lead to variation in reproductive compatibility between
      mates and reproductive isolation between members of different species. Previous
      studies in mice and other mammals have focused in particular on evidence for
      positive or diversifying selection that shapes the evolution of genes that encode
      sperm-binding proteins expressed in the egg coat or zona pellucida (ZP). By
      fitting phylogenetic models of codon evolution to data from the 1000 Genomes
      Project, we identified candidate sites evolving under diversifying selection in
      the human genes ZP3 and ZP2. We also identified one candidate site under positive
      selection in C4BPA, which encodes a repetitive protein similar to the mouse
      protein ZP3R that is expressed in the sperm head and binds to the ZP at
      fertilization. Results from several additional analyses that applied population
      genetic models to the same data were consistent with the hypothesis of selection
      on those candidate sites leading to coevolution of sperm- and egg-expressed
      genes. By contrast, we found no candidate sites under selection in a fourth gene
      (ZP1) that encodes an egg coat structural protein not directly involved in sperm
      binding. Finally, we found that two of the candidate sites (in C4BPA and ZP2)
      were correlated with variation in family size and birth rate among Hutterite
      couples, and those two candidate sites were also in linkage disequilibrium in the
      same Hutterite study population. All of these lines of evidence are consistent
      with predictions from a previously proposed hypothesis of balancing selection on
      epistatic interactions between C4BPA and ZP3 at fertilization that lead to the
      evolution of co-adapted allele pairs. Such patterns also suggest specific
      molecular traits that may be associated with both natural reproductive variation
      and clinical infertility.

PMID- 29340254
TI  - Response of methane production via propionate oxidation to carboxylated
      multiwalled carbon nanotubes in paddy soil enrichments.
AB  - Carboxylated multiwalled carbon nanotubes (MWCNTs-COOH) have become a growing
      concern in terms of their fate and toxicity in aqueous environments. Methane
      (CH4) is a major product of organic matter degradation in waterlogged
      environments. In this study, we determined the effect of MWCNTs-COOH on the
      production of CH4 from propionate oxidation in paddy soil enrichments. The
      results showed that the methanogenesis from propionate degradation was
      accelerated in the presence of MWCNTs-COOH. In addition, the rates of CH4
      production and propionate degradation increased with increasing concentrations of
      MWCNTs-COOH. Scanning electron microscopy (SEM) observations showed that the
      cells were intact and maintained their structure in the presence of MWCNTs-COOH.
      In addition, SEM and fluorescence in situ hybridization (FISH) images revealed
      that the cells were in direct contact with the MWCNTs and formed cell-MWCNTs
      aggregates that contained both bacteria and archaea. On the other hand, nontoxic
      magnetite nanoparticles (Fe3O4) had similar effects on the CH4 production and
      cell integrity as the MWCNTs-COOH. Compared with no nanomaterial addition, the
      relative abundances of Geobacter and Methanosarcina species increased in the
      presence of MWCNTs-COOH. This study suggests that MWCNTs-COOH exerted positive
      rather than cytotoxic effects on the syntrophic oxidation of propionate in paddy
      soil enrichments and affected the bacterial and archaeal community structure at
      the test concentrations. These findings provide novel insight into the
      consequences of nanomaterial release into anoxic natural environments.

PMID- 29340255
TI  - Habitat use in south-west European skinks (genus Chalcides).
AB  - Background: Congeneric species of reptiles frequently exhibit partitioning in
      terms of their use of habitats or trophic resources in order to reduce
      competition. In this study, we investigated habitat use by two species of
      European skinks: Chalcides bedriagai and Chalcides striatus, based on 49 records
      from southern France, Spain, and Portugal. Methods: We measured three levels of
      niche descriptors: macroscale (climate, topography, and substrate), mesoscale
      (plant associations), and microscale (vegetation cover and shelters). We assessed
      the associations between these environmental descriptors and the occurrence of
      the skinks. Results: Our results showed that the two species occupied opposite
      extremes of the ecological gradient i.e., C. bedriagai in semi-arid environments
      and C. striatus in temperate-oceanic environments, but there was broad ecological
      overlap in transitional climates at all of the habitat scales examined. This
      overlap was demonstrated by the presence of syntopy in geographically distant
      sites with different environmental characteristics. Discussion: The morphological
      differences between the two species, and possibly their different use of
      microhabitats, might favor this mesoscale overlap between congeneric species,
      which is relatively unusual in Mediterranean lizards.

PMID- 29340256
TI  - Clinical Cholecystitis in the Absence of the Gallbladder.
AB  - The congenital absence of the gallbladder (CAG) is a rare condition with an
      incidence of 13-65 cases/ 100,000 in the general population. This occurs when the
      gallbladder and the cystic duct fail to bud from the common bile duct during the
      fifth week of gestation. Most commonly, the patients with congenital absence of
      the gallbladder are asymptomatic. When symptomatic, they present as biliary
      colic, dyspepsia, jaundice or very rarely as acute cholecystitis. We present a
      case of a 27-year-old female who presented with acute right upper quadrant
      abdominal pain. Further evaluation with an ultrasound revealed a contracted
      gallbladder with stones. The hepatobiliary iminodiacetic acid scan was
      significant for non-visualization of the gallbladder, consistent with cystic duct
      obstruction. The laparoscopic cholecystectomy was attempted, however, the
      gallbladder was not visualized, and the procedure was aborted. The post-operative
      magnetic resonant cholangiopancreatography was consistent with the diagnosis of
      congenital absence of gallbladder.

PMID- 29340257
TI  - Symmetrical Drug-related Intertriginous and Flexural Exanthema Induced by
      Doxycycline.
AB  - Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) is a
      cutaneous drug reaction characterized by erythema over the buttocks, thighs,
      groin, and flexural regions most commonly associated with the use of beta-lactam
      antibiotics. Although the exact pathophysiology of this disease remains unknown,
      it is theorized to be the result of a delayed hypersensitivity response
      presenting as a cutaneous eruption days to weeks after exposure to the drug. The
      treatment involves discontinuation of the suspected medication, symptomatic
      control of pruritus, and topical steroid therapy. A 51-year-old woman with
      homocystinuria and fibromyalgia was admitted with fevers, pancytopenia (later
      diagnosed to be acute myelogenous leukemia), and a targetoid cutaneous eruption
      in the setting of a recent tick bite. She was subsequently noted to have
      symmetric, pruritic, erythematous papules over the lateral neck, retroauricular
      regions, lateral aspects of the inframammary regions, medial upper arms, axillae,
      and the lower abdomen two weeks after starting doxycycline. Considering the
      morphology, distribution, and intense pruritis associated with the eruption, a
      diagnosis of SDRIFE was made. Doxycycline discontinuation along with topical
      steroid therapy resulted in the resolution of the eruption and pruritus. Given
      the widespread use of doxycycline, clinicians should be aware of this possible
      side effect.

PMID- 29340258
TI  - Atypical Initial Presentation of Painful Muscle Cramps in a Patient with
      Amyotrophic Lateral Sclerosis: A Case Report and Brief Review of the Literature.
AB  - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized
      clinically by progressive muscle weakness that can occur proximally or distally
      in either the upper or lower extremities. It includes both upper motor neuron
      signs (spasticity, hyperreflexia, clonus, and Babinski sign) and lower motor
      neuron signs (atrophy, weakness, and muscle fasciculation). Initial presentation
      of progressively painful muscle cramps should lead the physician to screen for
      other signs of amyotrophic lateral sclerosis. We report the case of a 51-year-old
      male, who presented with dull muscle cramps in the right upper shoulder and arm.
      After a careful history and physical exam, it was found that patient had both
      upper and lower motor neuron signs; therefore, a diagnosis of amyotrophic lateral
      sclerosis was made. Amyotrophic lateral sclerosis should strongly be considered
      in the differential diagnosis of patients presenting with an atypical initial
      presentation of progressively painful muscle cramps.

PMID- 29340260
TI  - Nutritional status is associated with the return home in a long-term care health
      facility.
AB  - Background: The purpose of this study was to determine the association between
      nutritional status and the return home of older people living in a long-term care
      health facility (LCHF). Methods: A nested case control study was performed in 116
      people >=65 years of age in a single LCHF. Nutritional status was assessed using
      the Mini Nutritional Assessment Short Form (MNA-SF) and activities of daily
      living by the Functional Independence Measure (FIM). The return home, duration of
      rehabilitation, and the family wanting the patient to return home were obtained
      from clinical records. Multivariate logistic regression analysis was used to
      assess whether malnutrition had independent effects on the return home. Results:
      The participants included 36 males and 80 females with a mean age of 82 years.
      Thirty-seven people returned home while 79 did not. The MNA-SF showed that 80
      subjects were malnourished. Sixty-six of the participants received rehabilitation
      for longer than 1 hour per week, while 50 received rehabilitation for <1 hour.
      The proportion of subjects with malnutrition who returned home was significantly
      lower (P = .003) than in participants who did not return home. Multivariate
      logistic regression analysis showed that malnutrition (adjusted odds ratio [AOR],
      0.23; 95% confidence interval [CI], 0.08-0.65; P = .006), total FIM score (AOR,
      1.03; 95% CI, 1.01-1.06; P = .012), and the family wanting the patient to return
      home (AOR, 9.46; 95% CI, 3.19-28.12; P < .001) were independently associated with
      the return home. Conclusions: Nutritional status is associated with the return
      home in older people living in LCHF.

PMID- 29340259
TI  - Relationships between road-distance to primary care facilities and ischemic heart
      disease and stroke mortality in Hokkaido, Japan: A Bayesian hierarchical approach
      to ecological count data.
AB  - Objective: Poor access to a primary care physician may lead to poor control of
      risk factors for disease. This study investigated whether geographic access to a
      primary care physician was related to ischemic heart disease and stroke
      mortality. Methods: Road-distances from the centroids of the basic unit blocks of
      the 2010 Japanese Census to the nearest primary care facilities in Hokkaido,
      northern Japan, were measured using geographic information system (GIS) software.
      Next, block population-weighted mean road-distances to primary care facilities in
      all municipalities were calculated. The numbers of deaths from ischemic heart
      disease and stroke were obtained from the Vital Statistics Bureau. A Bayesian
      spatial conditional autoregressive (CAR) model was used to analyze relative risk
      (RR) by road-distance with the numbers of physicians in the municipality included
      as a covariate. Results: Relative risk (per 1 kilometer increased) of death from
      ischemic heart disease to road-distance to the nearest primary care facility was
      not significantly higher in men (1.108: 95% credible interval [CI] 0.999-1.037)
      and women (1.023: 95% CI 1.000-1.046). However, RR of death from stroke was
      significantly higher in men (1.019: 95% CI 1.005-1.032) and women (1.019: 95% CI
      1.006-1.033). Conclusion: Longer road-distance to a primary care facility may
      increase the risk of stroke mortality.

PMID- 29340261
TI  - Medical support with acupuncture and massage therapies for disaster victims.
AB  - Background: After the Great East Japan Earthquake and Tsunami Disaster (GEJED)
      and Joso City Flood (JCF), a number of people were relocated to evacuation
      centers. In situations following a large-scale disaster, acupuncture can be
      applied for various health problems in evacuation centers. In this study, we
      report the medical support operation for evacuees with acupuncture and massage
      therapy (AP/MT) and its effectiveness. In addition, we propose an experience
      based guideline for AP/MT in such situations. Methods: We retrospectively
      investigated the treatment with AP/MT after GEJED and JCF based on the medical
      records that were coded. We performed AP/MT for evacuees or supporters in Iwanuma
      City, Shiogama City, and Natori City after the GEJED (total number of 1042), and
      in Joso City after the JCF (total number of 110). Results: The most common
      complaints, shoulder, back, and knee pain, were reported in 67.6% of patients
      after the GEJED and 80.9% of patients after the JCF. Acupuncture and massage
      therapy (AP/MT) significantly decreased the median Face Scale score of subjective
      symptoms in evacuees (before, 3.0 vs after, 1.0, P < .001) and supporters
      (before, 3.0 vs after, 1.0, P < .001) in the JCF. Conclusions: Evacuees and
      supporters in affected areas could benefit from AP/MT for relief of subjective
      symptoms. For proper management and safety support, we proposed a guideline of
      AP/MT for postdisaster situations.

PMID- 29340262
TI  - Recovery from a depressive episode during postgraduate residency training is
      associated with senior doctors' support.
AB  - Background: Depression among doctors in residency training can have significant
      impacts on the health of the residents and on patient safety. This study aimed to
      investigate factors associated with recovery from a depressive episode
      experienced during postgraduate residency training. Methods: A questionnaire was
      administered to 2935 first-year residents at the beginning of residency training
      in 2011; follow-up surveys were conducted after 3 months and at the end of the
      training in 2013. The questionnaire included the Center for Epidemiologic Studies
      Depression Scale and the Senior Doctor's Support Scale (SDSS). Logistic
      regression was used to identify associations between factors that may have been
      related to recovery from depressive episodes. Results: A total 182 residents
      experienced a depressive episode in the 3 months after starting residency
      training. When reassessed at the end of the 2-year training, 102 (56%) residents
      had recovered from the episode and 80 (44%) had not. Increased odds of recovery
      were associated with a middle or high score on the SDSS (middle score odds ratios
      [OR] 4.45, 95% confidence interval [CI] 1.0-18.0, P = .04; and high score OR
      5.70, 95% CI 1.4-23.4, P = .02). Conclusions: Support from senior doctors should
      be enhanced to optimize recovery from depressive episodes experienced after the
      start of residency training.

PMID- 29340263
TI  - Diagnostic delay for imported malaria: A case of Plasmodium falciparum malaria
      misdiagnosed as common cold.
AB  - A 37-year-old Japanese man experienced fever and headache 8 days after returning
      to Japan following a 6-month stay in Nigeria. He visited two clinics but was sent
      home from each with a diagnosis of common cold. He was eventually brought to the
      emergency department with an altered mental status. Severe P. falciparum malaria
      was confirmed; his initial parasitemia index was 5.4%. He recovered fully with
      antimalarial treatment. This case suggests that primary care physicians should
      obtain recent travel history and consider malaria for any febrile patient who has
      returned from a malaria-endemic area.

PMID- 29340264
TI  - Reactive nonsexually related acute genital ulcers.
AB  - The case of a 19-year-old Japanese woman with reactive nonsexually related acute
      genital ulcers.

PMID- 29340265
TI  - Acute generalized pustular bacterid.
AB  - The case of a 70-year-old Japanese man with acute generalized pustular bacterid.

PMID- 29340266
TI  - 18F-FDG PET-CT in a patient with methotrexate-associated lymphoproliferative
      disorder.
AB  - 18F-FDG PET-CT clearly demonstrated the disease activity of MTX-LPD.

PMID- 29340267
TI  - Postherpetic abdominal pseudohernia: A diagnostic pitfall.
AB  - The accurate diagnosis of postherpetic abdominal pseudohernia, the rare
      complication of herpes zoster, is essential to avoid unnecessary imaging studies
      or surgery. Close observation and waiting for complete recovery are warranted
      considering the disease's self-resolving nature and favorable prognosis.

PMID- 29340268
TI  - Out with the old, in with the new: Assessing change in screen time when
      measurement changes over time.
AB  - We examined if screen time can be assessed over time when the measurement
      protocol has changed to reflect advances in technology. Beginning in 2011, 929
      youth (9-12 years at time one) living in in New Brunswick (Canada) self-reported
      the amount of time spent watching television (cycles 1-13), using computers
      (cycles 1-13), and playing video games (cycles 3-13). Using longitudinal
      invariance to test a shifting indicators model of screen time, we found that the
      relationships between the latent variable reflecting overall screen time and the
      indicators used to assess screen time were invariant across cycles (weak
      invariance). We also found that 31 out of 37 indicator intercepts were invariant,
      meaning that most indicators were answered similarly (i.e., on the same metric)
      across cycles (partial strong invariance), and that 28 out of 37 indicator
      residuals were invariant indicating that similar sources of error were present
      over time (partial strict invariance). Overall, across all survey cycles, 76% of
      indicators were fully invariant. Whereas issues were noted when new examples of
      screen-based technology (e.g., iPads) were added, having established partial
      invariance, we suggest it is still possible to assess change in screen time
      despite having changing indicators over time. Although it is not possible to draw
      definitive conclusions concerning other self-report measures of screen time, our
      findings may assist other researchers considering modifying self-report measures
      in longitudinal studies to reflect technological advancements and increase the
      precision of their results.

PMID- 29340269
TI  - Examining relationships between perceptions and objective assessments of
      neighborhood environment and sedentary time: Data from the Washington, D.C.
      Cardiovascular Health and Needs Assessment.
AB  - Sedentary time (ST) and neighborhood environment (NE) are predictors of
      cardiovascular (CV) health. However, little is known about ST's relationship with
      NE. We examined associations of perceived and objective NE with ST in the
      predominantly African American faith-based population of the Washington, D.C. CV
      Health and Needs Assessment. After using community-based research principles,
      participants reported NE perceptions, including sidewalks, recreational areas,
      and crime presence. Factor analysis was conducted to explore pertinent
      constructs; factor sums were created and combined as Total Perception Score (TPS)
      (higher score = more favorable perception). Objective NE was assessed using
      Google Maps and the Active Neighborhood Checklist (ANC). ST was self-reported.
      Linear regression determined relationships between TPS and ST, and ANC scores and
      ST, for 1) overall population, 2) lower median-income D.C. areas, and 3) higher
      median-income DC and Maryland areas. For the sample (N = 98.9% African-American,
      78% female), lower median-income areas had significantly lower mean TPS and ANC
      scores than higher median-income areas (p < 0.001). Three factors (neighborhood
      violence, physical/social environment, and social cohesion) were associated with
      overall NE perception. Among those in lower median-income areas, there was a
      negative association between TPS and ST that remained after covariate adjustment;
      this was not observed in higher median-income areas. There was no association
      between ANC scores and ST. Poorer NE perception is associated with greater ST for
      those in lower income areas, while objective environment is not related to ST.
      Multi-level interventions are needed to improve NE perceptions in lower-median
      income areas, reduce ST, and improve CV health.

PMID- 29340270
TI  - Outpatient, combined use of opioid and benzodiazepine medications in the United
      States, 1993-2014.
AB  - The combined use of opioid and benzodiazepine medications increases the risk of
      hazardous effects, such as respiratory depression. Although recent increases in
      outpatient use of opioid prescriptions have been documented, there are limited
      data regarding rates and correlates of combined opioid and benzodiazepines among
      adults in outpatient settings. Our objective was to examine annual trends in
      outpatient visits including opioids, benzodiazepines, and their combination among
      adults as well as clinical and demographic correlates. We used data from the 1993
      2014 National Ambulatory Medical Care Survey (NAMCS) among non-elderly (i.e.,
      ages 18-64 years) adults to examine the probability of a visit including an
      opioid, benzodiazepine, or their combination, in addition to clinical and
      demographic correlates. From 1993 to 2014, benzodiazepines-with-opioids visits
      increased from 9.8 to 62.5 (OR = 9.23, 95% CI = 5.45-15.65) per 10,000 visits.
      Highest-represented groups among benzodiazepines-with-opioids visits were older
      (50-64 years) (49.1%), white (88.8%), commercially insured (58.0%) patients
      during their first visit (87.6%) to a primary-care physician (41.9%). We
      identified a significant increase in the outpatient co-prescription of opioids
      and benzodiazepines, notably among adults aged 50-64 years during primary-care
      visits. Educational and policy changes to provide alternatives to benzodiazepine
      with-opioid co-prescription and limiting opioid prescription to pain specialists
      may reduce rates of this potentially hazardous combination.

PMID- 29340271
TI  - Transit use and physical activity: Findings from the Houston travel-related
      activity in neighborhoods (TRAIN) study.
AB  - Transportation-related physical activity can significantly increase daily total
      physical activity through active transportation or walking/biking to transit
      stops. The purpose of this study was to assess the relations between transit-use
      and self-reported and monitor-based physical activity levels in a predominantly
      minority population from the Houston Travel-Related Activity in Neighborhoods
      (TRAIN) Study. This was a cross-sectional analysis of 865 adults living in
      Houston, Texas between 2013 and 2015. The exposure variable was transit-use (non
      users, occasional users, and primary users). Self-reported and accelerometer
      determined physical activity were the outcomes of interest. Regression models
      adjusting for age, sex, race/ethnicity, and other covariates of interest were
      built to test the hypothesis that transit user status was directly associated
      with 1) minutes of moderate-intensity physical activity and 2) the prevalence of
      achieving the physical activity guidelines. The majority of participants were
      female, non-Hispanic black, and almost one-third had a high school education or
      less. After adjustment, primary transit-use was associated with 134.2 (p < 0.01)
      additional mean minutes per week of self-reported moderate-intensity
      transportation-related physical activity compared to non-users. Further, primary
      users had 7.3 (95% CI: 2.6-20.1) times the relative adjusted odds of meeting
      physical activity recommendations than non-users based on self-reported
      transportation-related physical activity. There were no statistically significant
      associations of transit-use with self-reported leisure-time or accelerometer
      derived physical activity. Transit-use has the potential for a large public
      health impact due to its sustainability and scalability. Therefore, encouraging
      the use of transit as a means to promote physical activity should be examined in
      future studies.

PMID- 29340272
TI  - Migraine-preventive prescription patterns by physician specialty in ambulatory
      care settings in the United States.
AB  - Many adults with migraine who require preventive therapy are often not prescribed
      the proper medications. The most likely reason is that primary care physicians
      are unacquainted with preventive medications for migraine. The present study
      assessed the migraine-preventive prescription patterns in office visits using
      data from the National Ambulatory Medical Care Survey from 2006 to 2009 in the
      United States. Patients who were 18 years or older and diagnosed with migraine
      were included in the analysis. In accordance with the recommendations of the
      headache guidelines, we included beta-blockers, antidepressants, triptans for
      short-term prevention of menstrual migraine, and other triptans for acute
      treatment. Weighted visits of adults with migraine prescribed with preventive
      medication ranged from 32.8% in 2006 to 38.6% in 2009. Visits to primary care
      physicians accounted for 72.6% of the analyzed adult migraine visits.
      Anticonvulsants (odds ratio [OR] 0.29, 95% confidence interval [CI] 0.14-0.57, p
      < 0.001) and triptans for menstrual migraine (OR 0.50, 95% CI 0.28-0.91, p =
      0.025) were less frequently prescribed by primary care physicians compared with
      specialty care physicians, such as neurologists and psychiatrists. There were no
      significant differences in the prescription patterns of antidepressants and beta
      blockers between primary and specialty care physicians. Beta-blockers were
      prescribed to patients with comorbidity of hypertension, and antidepressants were
      used by patients with comorbidity of depression. There are differences in the
      prescription patterns of certain type of preventive medications between primary
      care physicians and specialty care physicians.

PMID- 29340273
TI  - Effects of Portal Vein Thrombosis on the Outcomes of Liver Cirrhosis: A Mexican
      Perspective.

PMID- 29340274
TI  - Breaking through Restricting Bottleneck for Better Asthma Control.

PMID- 29340276
TI  - Clinical Value of Ultrasonography in Diagnosis of Pulmonary Embolism in
      Critically Ill Patients.
AB  - Pulmonary embolism (PE) is a clinical emergency that will increase the mortality
      if complicated with unstable hemodynamics. Because of its nonspecific clinical
      symptoms, it's a great challenge to make a PE diagnosis. The golden standard to
      diagnose PE is computed tomography of pulmonary artery (CTPA), but a diagnosis of
      PE also composed of evaluation of PE risk factors, possibilities, and risk
      stratification. Ultrasonography may detect right ventricle strain related to
      hemodynamic change, intravascular thrombosis, thrombosis in right heart or
      pulmonary arteries, pulmonary infarction, and local pleural effusion. Combination
      of ultrasound and traditional PE possibility evaluation score may further improve
      the pretest probability of CTPA. A comprehensive ultrasonography may sometimes
      rule out PE and may disclose other causes for the clinical situations. A heart
      lung-vessel-integrated multiorgan ultrasonography can help with the diagnosis of
      PE and so should be a necessary weapon for the physicians.

PMID- 29340275
TI  - Timing of Transjugular Intrahepatic Portosystemic Shunt for Budd-Chiari Syndrome:
      An Italian Hepatologist's Perspective.
AB  - Budd-Chiari syndrome (BCS) management flow-chart is derived from experts' opinion
      and is not evidence-based. Guidelines suggest BCS management should follow a
      stepwise strategy: medical therapy as first-line treatment, revascularization or
      transjugular intrahepatic portosystemic shunt (TIPS) if no response to medical
      therapy, and liver transplant as rescue therapy. Recent evidence suggests that
      only medical therapy results in a bad long-term outcome. The biggest criticism of
      guidelines is the indication that BCS should receive further treatment only when
      hemodynamic consequences of portal hypertension become clinically evident. Recent
      data support that in BCS liver fibrosis could arise from chronic microvascular
      ischemia. A reasoning model of BCS physiopathology is that impaired hepatic vein
      outflow has hemodynamic consequences on portal hypertension development and
      causes hepatic fibrosis and liver failure through chronic ischemic damage. On
      this assumption is the concept that relieving liver congestion could ameliorate
      liver function and prevent development of BCS complications. Recently, early
      interventional treatment with TIPS for BCS has been reported to be effective.
      Early TIPS seems to be the best option for BCS management. Future multicenter
      controlled studies should compare the outcome of BCS treated with early
      interventional treatment compared with stepwise strategy.

PMID- 29340277
TI  - Comparative Computed Flow Dynamic Analysis of Different Optimization Techniques
      in Left Main Either Provisional or Culotte Stenting.
AB  - Background and Objectives: Provisional and culotte are the most commonly used
      techniques in left main (LM) stenting. The impact of different post-dilation
      techniques on fluid dynamic of LM bifurcation has not been yet investigated. The
      aim of this study is to evaluate, by means of computational fluid dynamic
      analysis (CFD), the impact of different post-dilation techniques including
      proximal optimization technique (POT), kissing balloon (KB), POT-Side-POT and POT
      KB-POT, 2-steps Kissing (2SK) and Snuggle Kissing balloon (SKB) on flow dynamic
      profile after LM provisional or culotte stenting. Methods: We considered an LM
      LCA-LCX bifurcation reconstructed after reviewing 100 consecutive patients (mean
      age 71.4 +/- 9.3 years, 49 males) with LM distal disease. The diameters of LAD
      and LCX were modelled according to the Finnet's law as following: LM 4.5 mm, LAD
      3.5 mm, LCX 2.75 mm, with bifurcation angle set up at 55 degrees . Xience third
      generation stent (Abbot Inc., USA) was reconstructed and virtually implanted in
      provisional/cross-over and culotte fashion. POT, KB, POT-side-POT, POT-KB-POT,
      2SK and SKB were virtually applied and analyzed in terms of the wall shear stress
      (WSS). Results: Analyzing the provisional stenting, the 2SK and KB techniques had
      a statistically significant lower impact on the WSS at the carina, while POT
      seemed to obtain a neutral effect. In the wall opposite to the carina, the more
      physiological profile has been obtained by KB and POT with higher WSS value and
      smaller surface area of the lower WSS. In culotte stenting, at the carina, POT-KB
      POT and 2SK had a very physiological profile; while at the wall opposite to the
      carina, 2SK and POT-KB-POT decreased significantly the surface area of the lower
      WSS compared to the other techniques. Conclusion: From the fluid dynamic point of
      view in LM provisional stenting, POT, 2SK and KB showed a similar beneficial
      impact on the bifurcation rheology, while in LM culotte stenting, POT-KB-POT and
      2SK performed slightly better than the other techniques, probably reflecting a
      better strut apposition.

PMID- 29340278
TI  - Endoscopic Ultrasound-guided Pancreatic Pseudocyst Drainage with Lumen-apposing
      Metal Stents or Plastic Double-pigtail Stents: A Multifactorial Analysis.
AB  - Objective: To compare the efficiency of plastic and metal stents for symptomatic
      pancreatic pseudocyst (PP) drainage and analyze other main associated factors
      that affect the outcome of drainage therapy. Method: Rates of technical and
      clinical success, procedure-related side effects (hemorrhage, stent migration,
      and cyst rupture), reinterventions, and duration of hospital stay. Results: There
      were 52 patients, 40 patients underwent plastic stent placement and 12 patients
      underwent lumen-apposing metal stent (LAMS) placement. The total rate of
      technical success was 100%. The total rate of clinical success was 100%. The
      total rate of adverse events was 7.7% (4/52). On multiple logistic regression
      analysis, the use of plastic stents (P < 0.05, Exp B = 12.168) and the presence
      of a large cyst (P < 0.05, Exp B = 1.036) were shown to significantly increase
      the risk of reintervention. On multivariate linear regression analysis, etiology
      of pseudocyst (P < 0.05, B = -8.427, -9.785, -5.514) was associated with
      prolonged hospital stent, while stent type was not shown be a factor (P > 0.05).
      Conclusion: Both plastic and LAMSs are proven to be highly efficient in PP
      drainage. The LAMS is superior in preventing complications such as migration and
      cyst leakage and reducing the rate of reintervention.

PMID- 29340279
TI  - Effect of MTHFR A1298C and MTRR A66G Genetic Mutations on Homocysteine Levels in
      the Chinese Population: A Systematic Review and Meta-analysis.
AB  - Background and Objectives: The Chinese population typically has inadequate folate
      intake and no mandatory folic acid fortification. Methylenetetrahydrofolate
      reductase (MTHFR) and methionine synthase reductase (MTRR) are the two key
      regulatory enzymes in the folate/homocysteine (Hcy) metabolism. Hcy has been
      implicated in the pathogenesis of cardiovascular disease. We conducted a meta
      analysis to assess whether the MTHFR gene A1298C and the MTRR gene A66G
      polymorphisms affect Hcy levels in the Chinese population. Methods: This analysis
      included 13 studies with Hcy levels reported as one of the study measurements.
      Summary estimates of weighted mean differences and 95% confidence intervals (CIs)
      were obtained using random-effect models. Results: Overall, there were no
      significant differences in Hcy concentrations between participants with the MTHFR
      1298 CC (12 trials, n = 129), AA (n = 2166; beta, -0.51 MUmol/L; 95%CI: -2.14,
      1.11; P = 0.53), or AC genotype (n = 958; beta, 0.55 MUmol/L; 95%CI: -0.72, 1.82;
      P = 0.40). Consistently, compared to those with the MTRR 66 GG genotype (6
      trials, n = 156), similar Hcy concentrations were found in participants with the
      AA (n = 832; beta, -0.43 MUmol/L; 95%CI: -1.04, 0.17; P = 0.16) or AG (n =743;
      beta, -0.57 MUmol/L; 95%CI: -1.46, 0.31; P = 0.21) genotype. Similar results were
      observed for the dominant and recessive models. Conclusions: Neither the MTHFR
      A1298C polymorphism nor the MTRR A66G polymorphism affects Hcy levels in the
      Chinese population.

PMID- 29340280
TI  - Serum Vitamin D Levels in Treatment-naive Chronic Hepatitis B Patients.
AB  - Background and Objectives: According to the demographic health survey conducted
      in 2015, Egypt had 10% documented prevalence of anti-HBc positive patients aged 1
      59 and 1% viremic patients amongst the population in the same age group, with a
      domination of genotype D. Several studies claimed the possible role of vitamin D
      deficiency in hepatitis B virus (HBV) replication and disease progression.
      Patients and Methods: Serum vitamin D levels [25(OH D3] were assessed in 96 HBeAg
      negative non-cirrhotic chronic HBV patients and 25 healthy subjects classified as
      following: Group I: 48 chronic HBV patients with persistently normal ALT levels
      and HBV DNA level < 2000 IU/mL for >= 6 months; Group II: 48 chronic HBV patients
      with CHB with persistently elevated ALT and HBV DNA level >= 2000 IU/mL for >= 6
      months; and Group III: 25 apparently healthy subjects with normal liver enzymes
      and negative hepatitis viral markers were taken as the control group. Results:
      Vitamin D was much more deficient in group II than in group I and group III being
      11.55 +/- 3.97 ng/mL, 15.03 +/- 3.45, 27.00 +/- 6.76 ng/mL (P < 0.001),
      respectively, and a strong negative correlation was observed between vitamin D
      levels and HBV DNA levels (P = 0.043) in groups I and II. Conclusion: The current
      study showed high HBV DNA replication in patients with vitamin D deficiency
      suggesting the antimicrobial immunomodulatory role of vitamin D.

PMID- 29340281
TI  - Urgent Need to Define Pretreatment Predictors of Immune Check Point Inhibitors
      Related Endocrinopathies: A Case Report and Review of Literature.
AB  - Immune check point inhibitors have revolutionized the treatment of metastatic
      malignancies. They are a promising area in oncology and more drugs are likely to
      be available in the coming years. Along with the promise of better response
      oncologically, there is an increased incidence of endocrinopathies related to
      autoimmunity. This case report illustrates the dramatic development of
      hypothyroidism in a patient with underlying subclinical hyperthyroidism. It also
      suggests the potential pretreatment predictors of endocrinopathies related to
      these immune check point inhibitors.

PMID- 29340282
TI  - Should Vasoconstrictors be Considered in a Cirrhotic Patient with Acute Non
      variceal Upper Gastrointestinal Bleeding?
AB  - Varices manifest as a major etiology of upper gastrointestinal bleeding in
      patients with chronic liver diseases, such as liver cirrhosis and hepatocellular
      carcinoma. By contrast, non-variceal upper gastrointestinal bleeding is rare.
      Pharmacological treatment differs between patients with variceal and non-variceal
      bleeding. Vasoconstrictors are recommended for the treatment of variceal
      bleeding, rather than non-variceal bleeding. In contrast, pump proton inhibitors
      are recommended for the treatment of non-variceal bleeding, rather than variceal
      bleeding. Herein, we present a case with liver cirrhosis and acute upper
      gastrointestinal bleeding who had a high risk of rebleeding (i.e., Child-Pugh
      class C, hepatocellular carcinoma, portal vein thrombosis, low albumin, and high
      international normalized ratio and D-dimer). As the source of bleeding was
      obscure, only terlipressin without pump proton inhibitors was initially
      administered. Acute bleeding episode was effectively controlled. After that, an
      elective endoscopic examination confirmed that the source of bleeding was
      attributed to peptic ulcer, rather than varices. Based on this preliminary case
      report, we further discussed the potential role of vasoconstrictors in a patient
      with cirrhosis with acute non-variceal upper gastrointestinal bleeding.

PMID- 29340283
TI  - European Respiratory Society International Congress 2017: highlights from the
      Clinical Assembly.
AB  - This article contains highlights and a selection of the scientific advances from
      the European Respiratory Society's Clinical Assembly (Assembly 1 and its six
      respective groups) that were presented at the 2017 European Respiratory Society
      International Congress in Milan, Italy. The most relevant topics from each of the
      groups will be discussed, covering a wide range of areas including clinical
      problems, rehabilitation and chronic care, thoracic imaging, interventional
      pulmonology, diffuse and parenchymal lung diseases, and general practice and
      primary care. In this comprehensive review, the newest research and actual data
      as well as award-winning abstracts and highlight sessions will be discussed.

PMID- 29340284
TI  - Optical imaging during toddlerhood: brain responses during naturalistic social
      interactions.
AB  - Despite the importance of our ability to interact and communicate with others,
      the early development of the social brain network remains poorly understood. We
      examined brain activity in 12- to 14-month-old infants while they were
      interacting live with an adult in two different naturalistic social scenarios
      (i.e., reading a picture book versus singing nursery rhymes with gestures), as
      compared to baseline (i.e., showing infants a toy without eye contact or speech).
      We used functional near-infrared spectroscopy (fNIRS) recorded over the right
      temporal lobe of infants to assess the role of the superior temporal sulcus
      temporoparietal junction (STS-TPJ) region during naturalistic social
      interactions. We observed increased cortical activation in the STS-TPJ region to
      live social stimuli in both socially engaging conditions compared to baseline
      during real life interaction, with greater activation evident for the joint
      attention (reading book) condition relative to the social nursery rhymes. These
      results supported the view that the STS-TPJ region, engaged in the cortical
      social brain network, is already specialized in infants for processing social
      signals and is sensitive to communicative situations. This study also highlighted
      the potential of fNIRS for studying brain function in infants entering
      toddlerhood during live social interaction.

PMID- 29340285
TI  - Quantitative bone scan lesion area as an early surrogate outcome measure
      indicative of overall survival in metastatic prostate cancer.
AB  - A clinical validation of the bone scan lesion area (BSLA) as a quantitative
      imaging biomarker was performed in metastatic castration-resistant prostate
      cancer (mCRPC). BSLA was computed from whole-body bone scintigraphy at baseline
      and week 12 posttreatment in a cohort of 198 mCRPC subjects (127 treated and 71
      placebo) from a clinical trial involving a different drug from the initial
      biomarker development. BSLA computation involved automated image normalization,
      lesion segmentation, and summation of the total area of segmented lesions on bone
      scan AP and PA views as a measure of tumor burden. As a predictive biomarker,
      treated subjects with baseline BSLA [Formula: see text] had longer survival than
      those with higher BSLA ([Formula: see text] and [Formula: see text]). As a
      surrogate outcome biomarker, subjects were categorized as progressive disease
      (PD) if the BSLA increased by a prespecified 30% or more from baseline to week 12
      and non-PD otherwise. Overall survival rates between PD and non-PD groups were
      statistically different ([Formula: see text] and [Formula: see text]). Subjects
      without PD at week 12 had longer survival than subjects with PD: median 398 days
      versus 280 days. BSLA has now been demonstrated to be an early surrogate outcome
      for overall survival in different prostate cancer drug treatments.

PMID- 29340286
TI  - Cancer imaging phenomics toolkit: quantitative imaging analytics for precision
      diagnostics and predictive modeling of clinical outcome.
AB  - The growth of multiparametric imaging protocols has paved the way for
      quantitative imaging phenotypes that predict treatment response and clinical
      outcome, reflect underlying cancer molecular characteristics and spatiotemporal
      heterogeneity, and can guide personalized treatment planning. This growth has
      underlined the need for efficient quantitative analytics to derive high
      dimensional imaging signatures of diagnostic and predictive value in this
      emerging era of integrated precision diagnostics. This paper presents cancer
      imaging phenomics toolkit (CaPTk), a new and dynamically growing software
      platform for analysis of radiographic images of cancer, currently focusing on
      brain, breast, and lung cancer. CaPTk leverages the value of quantitative imaging
      analytics along with machine learning to derive phenotypic imaging signatures,
      based on two-level functionality. First, image analysis algorithms are used to
      extract comprehensive panels of diverse and complementary features, such as
      multiparametric intensity histogram distributions, texture, shape, kinetics,
      connectomics, and spatial patterns. At the second level, these quantitative
      imaging signatures are fed into multivariate machine learning models to produce
      diagnostic, prognostic, and predictive biomarkers. Results from clinical studies
      in three areas are shown: (i) computational neuro-oncology of brain gliomas for
      precision diagnostics, prediction of outcome, and treatment planning; (ii)
      prediction of treatment response for breast and lung cancer, and (iii) risk
      assessment for breast cancer.

PMID- 29340287
TI  - Fully automated detection of breast cancer in screening MRI using convolutional
      neural networks.
AB  - Current computer-aided detection (CADe) systems for contrast-enhanced breast MRI
      rely on both spatial information obtained from the early-phase and temporal
      information obtained from the late-phase of the contrast enhancement. However,
      late-phase information might not be available in a screening setting, such as in
      abbreviated MRI protocols, where acquisition is limited to early-phase scans. We
      used deep learning to develop a CADe system that exploits the spatial information
      obtained from the early-phase scans. This system uses three-dimensional (3-D)
      morphological information in the candidate locations and the symmetry information
      arising from the enhancement differences of the two breasts. We compared the
      proposed system to a previously developed system, which uses the full dynamic
      breast MRI protocol. For training and testing, we used 385 MRI scans, containing
      161 malignant lesions. Performance was measured by averaging the sensitivity
      values between 1/8-eight false positives. In our experiments, the proposed system
      obtained a significantly ([Formula: see text]) higher average sensitivity
      ([Formula: see text]) compared with that of the previous CADe system ([Formula:
      see text]). In conclusion, we developed a CADe system that is able to exploit the
      spatial information obtained from the early-phase scans and can be used in
      screening programs where abbreviated MRI protocols are used.

PMID- 29340288
TI  - 7T MRI subthalamic nucleus atlas for use with 3T MRI.
AB  - Deep brain stimulation (DBS) of the subthalamic nucleus (STN) reduces motor
      symptoms in most patients with Parkinson disease (PD), yet may produce untoward
      effects. Investigation of DBS effects requires accurate localization of the STN,
      which can be difficult to identify on magnetic resonance images collected with
      clinically available 3T scanners. The goal of this study is to develop a high
      quality STN atlas that can be applied to standard 3T images. We created a high
      definition STN atlas derived from seven older participants imaged at 7T. This
      atlas was nonlinearly registered to a standard template representing 56 patients
      with PD imaged at 3T. This process required development of methodology for
      nonlinear multimodal image registration. We demonstrate mm-scale STN localization
      accuracy by comparison of our 3T atlas with a publicly available 7T atlas. We
      also demonstrate less agreement with an earlier histological atlas. STN
      localization error in the 56 patients imaged at 3T was less than 1 mm on average.
      Our methodology enables accurate STN localization in individuals imaged at 3T.
      The STN atlas and underlying 3T average template in MNI space are freely
      available to the research community. The image registration methodology developed
      in the course of this work may be generally applicable to other datasets.

PMID- 29340289
TI  - Automatic segmentation method of pelvic floor levator hiatus in ultrasound using
      a self-normalizing neural network.
AB  - Segmentation of the levator hiatus in ultrasound allows the extraction of
      biometrics, which are of importance for pelvic floor disorder assessment. We
      present a fully automatic method using a convolutional neural network (CNN) to
      outline the levator hiatus in a two-dimensional image extracted from a three
      dimensional ultrasound volume. In particular, our method uses a recently
      developed scaled exponential linear unit (SELU) as a nonlinear self-normalizing
      activation function, which for the first time has been applied in medical imaging
      with CNN. SELU has important advantages such as being parameter-free and mini
      batch independent, which may help to overcome memory constraints during training.
      A dataset with 91 images from 35 patients during Valsalva, contraction, and rest,
      all labeled by three operators, is used for training and evaluation in a leave
      one-patient-out cross validation. Results show a median Dice similarity
      coefficient of 0.90 with an interquartile range of 0.08, with equivalent
      performance to the three operators (with a Williams' index of 1.03), and
      outperforming a U-Net architecture without the need for batch normalization. We
      conclude that the proposed fully automatic method achieved equivalent accuracy in
      segmenting the pelvic floor levator hiatus compared to a previous semiautomatic
      approach.

PMID- 29340290
TI  - Tailoring four-dimensional cone-beam CT acquisition settings for fiducial marker
      based image guidance in radiation therapy.
AB  - Use of four-dimensional cone-beam CT (4D-CBCT) and fiducial markers for image
      guidance during radiation therapy (RT) of mobile tumors is challenging due to the
      trade-off among image quality, imaging dose, and scanning time. This study aimed
      to investigate different 4D-CBCT acquisition settings for good visibility of
      fiducial markers in 4D-CBCT. Using these 4D-CBCTs, the feasibility of marker
      based 4D registration for RT setup verification and manual respiration-induced
      motion quantification was investigated. For this, we applied a dynamic phantom
      with three different breathing motion amplitudes and included two patients with
      implanted markers. Irrespective of the motion amplitude, for a medium field of
      view (FOV), marker visibility was improved by reducing the imaging dose per
      projection and increasing the number of projection images; however, the scanning
      time was 4 to 8 min. For a small FOV, the total imaging dose and the scanning
      time were reduced (62.5% of the dose using a medium FOV, 2.5 min) without losing
      marker visibility. However, the body contour could be missing for a small FOV,
      which is not preferred in RT. The marker-based 4D setup verification was feasible
      for both the phantom and patient data. Moreover, manual marker motion
      quantification can achieve a high accuracy with a mean error of [Formula: see
      text].

PMID- 29340291
TI  - Erratum: Endoscopic esophagogastric anastomosis with luminal apposition Axios
      stent (LAS) approach: a new concept for hybrid "Lewis Santy".
AB  - [This corrects the article DOI: 10.1055/s-0043-106577.].

PMID- 29340293
TI  - Can sedation using a combination of propofol and dexmedetomidine enhance the
      satisfaction of the endoscopist in endoscopic submucosal dissection?
AB  - Background and study aims:  The aim of this pilot randomized controlled trial was
      to evaluate and compare the satisfaction of the endoscopist along with the
      effectiveness and safety of sedation between sedation protocol using a
      combination of propofol (PF) and dexmedetomidine (DEX) (Combination group) and
      sedation protocol using PF alone (PF group) during gastric endoscopic submucosal
      dissection (ESD). Patients and methods : Fifty-eight patients with gastric
      neoplasias scheduled for gastric ESD were enrolled and randomly assigned to the
      two groups. The satisfaction scores of the endoscopists and the parameters for
      the effectiveness and safety of sedation were evaluated by comparisons between
      the two groups. Results : The satisfaction scores of the endoscopists, which were
      measured using a visual analogue scale, were significantly higher in the
      Combination group than in the PF group (88 vs. 69, P  = 0.003). The maintenance
      dose of PF was lower in the Combination group than in the PF group (2 mg/kg/h vs.
      5 mg/kg/h, P  < 0.001), and the number of rescue PF injections was fewer in the
      Combination group than in the PF group (2 times vs. 6 times, P  < 0.001). The
      incidence of bradycardia (defined as a pulse rate <= 45 bpm) in the Combination
      group was higher than that in the PF group (37.9 % vs. 10.3 %, P  = 0.029).
      Conclusions : This study suggests that gastroenterologist-directed sedation using
      a combination of PF and DEX during gastric ESD can enhance the satisfaction
      levels of endoscopists by providing stable sedation with an acceptable safety
      profile.

PMID- 29340294
TI  - A comparison of endoscopic and non-endoscopic biliary intervention outcomes in
      patients with prior bariatric surgery.
AB  - Background and study aims : Endoscopic biliary intervention (BI) is often
      difficult to perform in patients with prior bariatric surgery (BRS). We sought to
      analyze outcomes of patients with prior BRS undergoing endoscopic and non
      endoscopic BI. Patients and methods:  The Nationwide Inpatient Sample (2007 -
      2011) was reviewed to identify all adult inpatients (>= 18 years) with a history
      of BRS undergoing BI. The clinical outcomes of interest were in-patient
      mortality, length of stay (LOS), and total hospital charges. Results:  There were
      7,343 patients with prior BRS who underwent BIs where a majority were endoscopic
      (4,482 vs. 2,861, P  < 0.01). The mean age was 50+/-30.8 years and the majority
      were females (80.5 %). Gallstone-related disease was the most common indication
      for BI and managed more often with primary endoscopic management (2,146 vs.
      1,132, P  < 0.01). Inpatient mortality was not significantly different between
      patients undergoing primary endoscopic versus non-endoscopic BI (0.2 % vs. 0.7 %,
      P  = 0.2). Patients with sepsis were significantly more likely to incur failed
      primary endoscopic BI (OR 2.74, 95 % CI 1.15, 6.53) and were more likely to be
      managed with non-endoscopic BI (OR 2.13, 95 % CI 1.3, 3.5). Primary non
      endoscopic BI and failed endoscopic BI were both associated with longer LOS (by
      1.77 days, P  < 0.01 and by 2.17 days, P  < 0.01, respectively) and higher
      hospitals charges (by $11,400, P  < 0.01 and by $ 14,200, P  < 0.01,
      respectively). Conclusion:  Primary endoscopic management may be a safe and cost
      effective approach for patients with prior BRS who need BI. While primary
      endoscopic biliary intervention is more common, primary non-endoscopic
      intervention may be used more often for sepsis.

PMID- 29340295
TI  - Usage characteristics and adverse event rates of the direct puncture and pull
      techniques for percutaneous endoscopic gastrostomy in patients with malignant
      tumors of the upper aerodigestive tract.
AB  - Background and study aims:  Patients with malignant tumors of the upper
      gastrointestinal tract are at risk of weight loss. Early supportive nutrition
      therapy is therefore recommended and usually requires placement of a percutaneous
      endoscopic gastrostomy (PEG). The aim of this study was to compare adverse events
      and usage characteristics of the direct puncture technique with those of the
      traditional pull technique when used in patients with endoscopically passable
      tumors. The primary endpoint was the rate of inflammatory adverse events (AEs) at
      the gastrostomy fistula. The secondary endpoint was the long-term rate of
      puncture-site metastases. Patients and methods:  One hundred twenty patients
      (median age 56; IQR 36, 86 years) were randomized and treated per protocol in
      this prospective open randomized single-center study. Follow-ups were conducted
      on the third and seventh post-interventional days, after 1, 3 and 6 months and
      the last follow-up 5 years after intervention. Results:  Within the short-term
      follow-up period of 6 months after PEG placement, AEs were noted in 47 patients
      (39.2 %). These included 22 inflammations and 16 device dislocations and were
      mainly found in the puncture group (33 vs. 14 in the pull group) with a
      significantly increased incidence in the first month after PEG insertion ( P  =
      0.001). Evaluation of the 5-year data did not reveal any significant differences.
      The gastrostomy tube was used in 101 patients (84.2 %) (range 18 days to 5
      years). Conclusions:  Our results favor the pull technique for patients with
      endoscopically passable tumors of the upper gastrointestinal tract due to less
      short-term adverse events. Both systems contributed equally to secure long-term
      use.

PMID- 29340296
TI  - Risk of colonic diverticular rebleeding according to endoscopic appearance.
AB  - Background and study aims:  Re-commencement of bleeding (rebleeding) of colonic
      diverticula after endoscopic hemostasis is a clinical problem. This study aimed
      to examine whether endoscopic visibility of colonic diverticular bleeding affects
      the risk of rebleeding after endoscopic hemostasis. Patients and methods:  We
      performed a retrospective review of endoscopic images and medical charts of
      patients with colonic diverticular bleeding who underwent endoscopic hemostasis.
      Endoscopic visibility was classified into two types according to visibility of
      the source of bleeding; source invisibility due to bleeding or attached hematin
      (type 1), or endoscopically visible responsive vessels (type 2). Rebleeding rates
      within one year after initial hemostasis were examined. Results:  Of 93 patients
      with successful endoscopic hemostasis, 38 (41 %) showed type 1 visibility, while
      the remaining presented type 2. All patients received hemostasis with clipping,
      rebleeding developed in 20 patients (22 %). Type 1 visibility was more likely to
      be observed in patients with rebleeding (65 % vs. 34 %, P  = 0.013). Multivariate
      analysis revealed that after endoscopic hemostasis, type 1 visibility (invisible
      source) was the only independent risk factor for colonic diverticular rebleeding
      (odds ratio, 3.05; 95 % confidence interval, 1.03 - 9.59, P  = 0.044). Kaplan
      Meier curve showed the cumulative incidence of rebleeding was significantly
      higher in patients with type 1 visibility than those with type 2 visibility ( P 
      = 0.0033, log-rank test). Conclusion:  Hemostasis by clipping for colonic
      diverticular bleeding without definite observation of the source of bleeding may
      not be sufficiently effective. Other hemostatic methods, including band ligation,
      should be considered when the source of bleeding is unclear.

PMID- 29340297
TI  - Acetic acid-guided biopsies in Barrett's surveillance for neoplasia detection
      versus non-targeted biopsies (Seattle protocol): A feasibility study for a
      randomized tandem endoscopy trial. The ABBA study.
AB  - Background and study aims : Barrett's esophagus is a potentially pre-cancerous
      condition, affecting 375,000 people in the UK. Patients receive a 2-yearly
      endoscopy to detect cancerous changes, as early detection and treatment results
      in better outcomes. Current treatment requires random mapping biopsies along the
      length of Barrett's, in addition to biopsy of visible abnormalities. As only 13 %
      of pre-cancerous changes appear as visible nodules or abnormalities, areas of
      dysplasia are often missed. Acetic acid chromoendoscopy (AAC) has been shown to
      improve detection of pre-cancerous and cancerous tissue in observational studies,
      but no randomized controlled trials (RCTs) have been performed to date. Patients
      and methods : A "tandem" endoscopy cross-over design. Participants will be
      randomized to endoscopy using mapping biopsies or AAC, in which dilute acetic
      acid is sprayed onto the surface of the esophagus, highlighting tissue through an
      whitening reaction and enhancing visibility of areas with cellular changes for
      biopsy. After 4 to 10 weeks, participants will undergo a repeat endoscopy, using
      the second method. Rates of recruitment and retention will be assessed, in
      addition to the estimated dysplasia detection rate, effectiveness of the
      endoscopist training program, and rates of adverse events (AEs). Qualitative
      interviews will explore participant and endoscopist acceptability of study design
      and delivery, and the acceptability of switching endoscopic techniques for
      Barrett's surveillance. Results : Endoscopists' ability to diagnose dysplasia in
      Barrett's esophagus can be improved. AAC may offer a simple, universally
      applicable, easily-acquired technique to improve detection, affording patients
      earlier diagnosis and treatment, reducing endoscopy time and pathology costs. The
      ABBA study will determine whether a crossover "tandem" endoscopy design is
      feasible and acceptable to patients and clinicians and gather outcome data to
      power a definitive trial.

PMID- 29340298
TI  - Efficacy and safety of sedation during endoscopic submucosal dissection of
      gastric cancers using a comparative trial of propofol versus midazolam.
AB  - Background and study aims : Proper sedation is necessary for the safe and
      satisfactory completion of endoscopic submucosal dissection (ESD) for early
      gastric cancer. This study was conducted as a comparative trial of efficacy and
      safety, comparing propofol-based sedation and midazolam-based sedation during ESD
      of early gastric cancer patients. Patients and methods : This study examined 64
      lesions in 58 patients treated using ESD with midazolam plus pentazocine between
      July 2013 and January 2014 (group M) and 237 lesions in 216 patients treated by
      ESD using propofol plus pentazocine between February 2014 and December 2015
      (group P). The two groups were compared in terms of the frequency of body
      movement during ESD as the primary outcome and in terms of the procedure time, en
      bloc resection rate, intraoperative change in cardiorespiratory dynamics, and
      postoperative awareness as the secondary outcomes. Body movement was defined as
      movement by a patient that required interruption of the procedure or restraint of
      the patient's body trunk, and addition of a sedative agent. Results : The median
      frequency of body movement during ESD was significantly lower in group P (0
      times) than in group M (3 times) ( P  < 0.001). No significant difference was
      found for the mean procedure time (117 min in group P; 127 min in group M).
      Although no significant difference was found in the incidence of hypoxemia,
      bradycardia, or bradypnea, the incidence of hypotension was significantly higher
      in group P (31.5 %) than in group M (6.9 %) ( P  = 0.004). Patients in group P
      had significantly higher postoperative awareness immediately after ESD and at 1
      hour after ESD ( P  = 0.002 and 0.022, respectively). Conclusion : These results
      demonstrate the efficacy and safety of propofol-based sedation for gastric ESD.

PMID- 29340299
TI  - Prospective study of the feasibility of point-of-care testing strategy for
      carbapenem-resistant organism detection.
AB  - Background/aims:  In an investigator-initiated, prospective study, we evaluated
      the feasibility of a five-gene sequence point-of-care (POC) testing strategy
      (Xpert CARBA-R Assay, Cepheid Inc., Sunnyvale, CA, USA), compared to reference
      laboratory PCR (48 - 72 hours turnaround time, two gene sequences), in patients
      undergoing endoscopic retrograde cholangiopancreatography (ERCP) and in a
      hospital outbreak investigation. Methods:  After informed consent, patients
      undergoing ERCP (September 2015 - April 2016, n = 191) at Mayo Clinic and
      potential hospital contacts (n = 9) of an index carbapenem-resistant organism
      (CRO)-positive inpatient were included. Two rectal swabs, one each for reference
      and POC assays were obtained. The Xpert CARBA-R Assay enables qualitative rapid
      detection of five beta-lactamase gene sequences associated with carbapenem-non
      susceptibility in Gram-negative bacteria. Feasibility parameters (specimen
      processing and assay run time, ease of use) and percent agreement between the
      tests were calculated using JMP Pro11 (SAS Corp, Cary, NC, USA). Results:  Mean
      age was 62 +/- 15 years; 108 (54 %) were male. Both tests were successfully
      performed in all patients. The POC test was rated by endoscopy nurses as
      easy/very easy to conduct in 193 patients (97 %); median assay run time and
      median time for specimen collection and processing were 55 minutes (interquartile
      range IQR: 53 - 55 minutes) and 3 minutes (IQR: 3 - 6 minutes), respectively. In
      200/201 (99.5 %) tests, there was agreement between the POC and reference PCR.
      Conclusions:  The more comprehensive POC CRO testing of patients in the endoscopy
      suite is feasible and results are available in < 1 hour. This strategy may enable
      rapid risk stratification of duodenoscope exposure to CRO and potentially improve
      operational efficiency and decrease costs.

PMID- 29340301
TI  - Stable organic thin-film transistors.
AB  - Organic thin-film transistors (OTFTs) can be fabricated at moderate temperatures
      and through cost-effective solution-based processes on a wide range of low-cost
      flexible and deformable substrates. Although the charge mobility of state-of-the
      art OTFTs is superior to that of amorphous silicon and approaches that of
      amorphous oxide thin-film transistors (TFTs), their operational stability
      generally remains inferior and a point of concern for their commercial
      deployment. We report on an exhaustive characterization of OTFTs with an
      ultrathin bilayer gate dielectric comprising the amorphous fluoropolymer CYTOP
      and an Al2O3:HfO2 nanolaminate. Threshold voltage shifts measured at room
      temperature over time periods up to 5.9 * 105 s do not vary monotonically and
      remain below 0.2 V in microcrystalline OTFTs (MUc-OTFTs) with field-effect
      carrier mobility values up to 1.6 cm2 V-1 s-1. Modeling of these shifts as a
      function of time with a double stretched-exponential (DSE) function suggests that
      two compensating aging mechanisms are at play and responsible for this high
      stability. The measured threshold voltage shifts at temperatures up to 75 degrees
      C represent at least a one-order-of-magnitude improvement in the operational
      stability over previous reports, bringing OTFT technologies to a performance
      level comparable to that reported in the scientific literature for other
      commercial TFTs technologies.

PMID- 29340300
TI  - Shared Mechanisms in the Estimation of Self-Generated Actions and the Prediction
      of Other's Actions by Humans.
AB  - The question of how humans predict outcomes of observed motor actions by others
      is a fundamental problem in cognitive and social neuroscience. Previous
      theoretical studies have suggested that the brain uses parts of the forward model
      (used to estimate sensory outcomes of self-generated actions) to predict outcomes
      of observed actions. However, this hypothesis has remained controversial due to
      the lack of direct experimental evidence. To address this issue, we analyzed the
      behavior of darts experts in an understanding learning paradigm and utilized
      computational modeling to examine how outcome prediction of observed actions
      affected the participants' ability to estimate their own actions. We recruited
      darts experts because sports experts are known to have an accurate outcome
      estimation of their own actions as well as prediction of actions observed in
      others. We first show that learning to predict the outcomes of observed dart
      throws deteriorates an expert's abilities to both produce his own darts actions
      and estimate the outcome of his own throws (or self-estimation). Next, we
      introduce a state-space model to explain the trial-by-trial changes in the darts
      performance and self-estimation through our experiment. The model-based analysis
      reveals that the change in an expert's self-estimation is explained only by
      considering a change in the individual's forward model, showing that an
      improvement in an expert's ability to predict outcomes of observed actions
      affects the individual's forward model. These results suggest that parts of the
      same forward model are utilized in humans to both estimate outcomes of self
      generated actions and predict outcomes of observed actions.

PMID- 29340302
TI  - Localized concentration reversal of lithium during intercalation into
      nanoparticles.
AB  - Nanoparticulate electrodes, such as Li x FePO4, have unique advantages over their
      microparticulate counterparts for the applications in Li-ion batteries because of
      the shortened diffusion path and access to nonequilibrium routes for fast Li
      incorporation, thus radically boosting power density of the electrodes. However,
      how Li intercalation occurs locally in a single nanoparticle of such materials
      remains unresolved because real-time observation at such a fine scale is still
      lacking. We report visualization of local Li intercalation via solid-solution
      transformation in individual Li x FePO4 nanoparticles, enabled by probing sub
      angstrom changes in the lattice spacing in situ. The real-time observation
      reveals inhomogeneous intercalation, accompanied with an unexpected reversal of
      Li concentration at the nanometer scale. The origin of the reversal phenomenon is
      elucidated through phase-field simulations, and it is attributed to the presence
      of structurally different regions that have distinct chemical potential
      functions. The findings from this study provide a new perspective on the local
      intercalation dynamics in battery electrodes.

PMID- 29340303
TI  - Highly mobile charge-transfer excitons in two-dimensional WS2/tetracene
      heterostructures.
AB  - Charge-transfer (CT) excitons at heterointerfaces play a critical role in light
      to electricity conversion using organic and nanostructured materials. However,
      how CT excitons migrate at these interfaces is poorly understood. We investigate
      the formation and transport of CT excitons in two-dimensional WS2/tetracene van
      der Waals heterostructures. Electron and hole transfer occurs on the time scale
      of a few picoseconds, and emission of interlayer CT excitons with a binding
      energy of ~0.3 eV has been observed. Transport of the CT excitons is directly
      measured by transient absorption microscopy, revealing coexistence of delocalized
      and localized states. Trapping-detrapping dynamics between the delocalized and
      localized states leads to stretched-exponential photoluminescence decay with an
      average lifetime of ~2 ns. The delocalized CT excitons are remarkably mobile with
      a diffusion constant of ~1 cm2 s-1. These highly mobile CT excitons could have
      important implications in achieving efficient charge separation.

PMID- 29340304
TI  - Pressure-induced shear and interlayer expansion in Ti3C2 MXene in the presence of
      water.
AB  - Pseudo-negative compressibility in layered materials is a phenomenon typically
      limited to in situ high-pressure experiments in some clay minerals and carbon
      based materials. We show that the MXene Ti3C2T x expands along its
      crystallographic c direction when compressed in the presence of H2O. This
      expansive effect occurs when a mixture of powders and excess water is quasi
      hydrostatically compressed in a diamond anvil cell; it also occurs to a much
      larger extent when powders are pressed uniaxially into discs and, notably,
      persists after pressure is released. We attribute the expansion to the insertion
      of H2O molecules and have identified shear-induced slipping of the nanosheets
      comprising multilayered MXene particles as a possible cause of this behavior in
      the latter case. This both has implications for the processing of MXenes and
      contributes to the field of materials with pseudo-negative compressibility by
      adding a new member for further investigation.

PMID- 29340305
TI  - Successful Drug-eluting Stent Implantation in a Male Patient with Dextrocardia: A
      Case Report.
AB  - Situs inversus with dextrocardia is a rare condition, with complete transposition
      of all the body organs, including the heart. Percutaneous coronary intervention
      (PCI) in these patients is technically difficult because of the mirror image of
      organs. Here, we describe a 56-year-old man with coronary heart disease with
      known situs inversus with dextrocardia and coronary percutaneous intervention was
      performed for stenosis in the right coronary artery. A drug eluting stent was
      implanted at this site successfully. This case suggested that the interventional
      management of such patients follows the same general rules as for non
      dextrocardia patients, but the manipulation of the catheter and projection
      position choices need to be taken into consideration to obtain optimal benefits
      for the patient.

PMID- 29340306
TI  - Iron Chelation Resulting in Renal Phosphate Wasting.

PMID- 29340307
TI  - A Patient With CKD Develops Cholestatic Liver Injury During a Clinical Trial.

PMID- 29340308
TI  - Noninfectious Peritoneal Dialysis Exit Site Rash-An Unusual Case Report and
      Review of the Literature.

PMID- 29340309
TI  - Strongyloides stercoralis-Associated Tip Variant Focal Segmental
      Glomerulosclerosis.

PMID- 29340310
TI  - Disseminated Adenovirus Nephritis After Kidney Transplantation.

PMID- 29340311
TI  - Hyponatremia and the Brain.
AB  - Hyponatremia is defined by low serum sodium concentration and is the most common
      electrolyte disorder encountered in clinical practice. Serum sodium is the main
      determinant of plasma osmolality, which, in turn, affects cell volume. In the
      presence of low extracellular osmolality, cells will swell if the adaptation
      mechanisms involved in the cell volume maintenance are inadequate. The most
      dramatic effects of hyponatremia on the brain are seen when serum sodium
      concentration decreases in a short period, allowing little or no adaptation. The
      brain is constrained inside a nonextensible envelope; thus, brain swelling
      carries a significant morbidity because of the compression of brain parenchyma
      over the rigid skull. Serum sodium concentration is an important determinant of
      several biological pathways in the nervous system, and recent studies have
      suggested that hyponatremia carries a significant risk of neurological impairment
      even in the absence of brain edema. The brain can also be affected by the
      treatment of hyponatremia, which, if not undertaken cautiously, could lead to
      osmotic demyelination syndrome, a rare demyelinating brain disorder that occurs
      after rapid correction of severe hyponatremia. This review summarizes the
      pathophysiology of brain complications of hyponatremia and its treatment.

PMID- 29340312
TI  - CKD Screening and Surveillance in Australia: Past, Present, and Future.
AB  - Chronic kidney disease (CKD) was largely a hidden health problem until the
      publication of an internationally agreed approach to its identification,
      monitoring, and treatment. The 2002 National Kidney Foundation CKD classification
      and the subsequent 2006 Kidney Disease Improving Global Outcomes (KDIGO)
      recommendations are powerful tools for translating thinking about CKD into
      clinical practice. These guidelines were strongly endorsed by the international
      community, including Australia, and were incorporated into CKD practice
      guidelines. In the past, CKD research studies in Australia focused on screening
      the general population, and more specifically, individuals at risk for CKD.
      Information from these studies led to the recognition that the CKD burden in
      Australia is a public health problem and contributed to the development of
      national health policies and priorities. At present, apart from the Australia and
      New Zealand Dialysis and Transplant Registry (ANZDATA) that reports on CKD
      patients undergoing renal replacement therapy (RRT), long-term surveillance to
      describe the natural history of the CKD population not on RRT has only recently
      started. Entities such as CKD. Queensland and the Western Australian Nephrology
      Database are able to fill the gap and provide opportunities for collaborative
      research of CKD in Australia. Establishment of a National Health and Medical
      Research Centre-funded CKD Centre of Excellence in 2015 and the Better Evidence
      and Translation-Chronic Kidney Disease in 2016 are likely to change the future of
      CKD surveillance and research in Australia.

PMID- 29340313
TI  - Treatment of Severe Hyperkalemia: Confronting 4 Fallacies.
AB  - Severe hyperkalemia is a medical emergency that can cause lethal arrhythmias.
      Successful management requires monitoring of the electrocardiogram and serum
      potassium concentrations, the prompt institution of therapies that work both
      synergistically and sequentially, and timely repeat dosing as necessary. It is of
      concern then that, based on questions about effectiveness and safety, many
      physicians no longer use 3 key modalities in the treatment of severe
      hyperkalemia: sodium bicarbonate, sodium polystyrene sulfonate (Kayexalate
      [Concordia Pharmaceuticals Inc., Oakville, ON, Canada], SPS [CMP Pharma,
      Farmville, NC]), and hemodialysis with low potassium dialysate. After reviewing
      older reports and newer information, I believe that these exclusions are ill
      advised. In this article, I briefly discuss the treatment of severe hyperkalemia
      and detail why these modalities are safe and effective and merit inclusion in the
      treatment of severe hyperkalemia.

PMID- 29340314
TI  - DNAJB9 Is a Specific Immunohistochemical Marker for Fibrillary
      Glomerulonephritis.
AB  - Introduction: Fibrillary glomerulonephritis (FGN) is a rare disease with unknown
      pathogenesis and a poor prognosis. Until now, the diagnosis of this disease has
      required demonstration of glomerular deposition of randomly oriented fibrils by
      electron microscopy that are Congo red negative and stain with antisera to Igs.
      We recently discovered a novel proteomic tissue biomarker for FGN, namely,
      DNAJB9. Methods: In this work, we developed DNAJB9 immunohistochemistry and
      tested its sensitivity and specificity for the diagnosis of FGN. This testing was
      performed on renal biopsy samples from patients with FGN (n = 84), amyloidosis (n
      = 21), a wide variety of non-FGN glomerular diseases (n = 98), and healthy
      subjects (n = 11). We also performed immunoelectron microscopy to determine
      whether DNAJB9 is localized to FGN fibrils. Results: Strong, homogeneous, smudgy
      DNAJB9 staining of glomerular deposits was seen in all but 2 cases of FGN. The 2
      cases that did not stain for DNAJB9 were unique, as they had glomerular staining
      for IgG only (without kappa or lambda) on immunofluorescence. DNAJB9 staining was
      not observed in cases of amyloidosis, in healthy subjects, or in non-FGN
      glomerular diseases (with the exception of very focal staining in 1 case of
      smoking-related glomerulopathy), indicating 98% sensitivity and > 99%
      specificity. Immunoelectron microscopy showed localization of DNAJB9 to FGN
      fibrils but not to amyloid fibrils or immunotactoid glomerulopathy microtubules.
      Conclusion: DNAJB9 immunohistochemistry is sensitive and specific for FGN.
      Incorporation of this novel immunohistochemical biomarker into clinical practice
      will now allow more rapid and accurate diagnosis of this disease.

PMID- 29340315
TI  - Contrast-Induced Nephropathy and Oxygen Pretreatment in Patients With Impaired
      Renal Function.
AB  - Introduction: Contrast-induced nephropathy is a complication following coronary
      angiography and percutaneous coronary intervention. Because contrast-induced
      nephropathy is a predictor of long-term mortality in patients with ischemic heart
      disease undergoing percutaneous coronary intervention, preventive strategies are
      required. We assessed the effects of periprocedural oxygenation on contrast
      induced nephropathy among patients with pre-existing renal dysfunction. Methods:
      A total of 200 consecutive patients with impaired renal function (estimated
      glomerular filtration < 60 ml/min per 1.73 m2) undergoing elective cardiovascular
      angiography were randomly assigned to an oxygenation treatment (n = 100) or
      control group (n = 100). In oxygenation treatment, pure oxygen (2 L/min) was
      administered for 10 minutes before exposure to contrast medium. The primary
      endpoint was the incidence of contrast-induced nephropathy, defined as a >= 25%
      increase in serum creatinine levels from baseline within 48 hours of exposure.
      Results: In the oxygenation treatment group, partial pressure of arterial oxygen
      was higher (135 +/- 25 mm Hg vs. 84 +/- 10 mm Hg, P < 0.001); contrast-induced
      nephropathy incidence was lower (1% vs. 8%, odds ratio [OR] = 0.12, 95%
      confidence interval [CI] = 0.01-0.95, P = 0.02); and partial pressure of arterial
      carbon dioxide and bicarbonate base lactate levels were similar compared with
      those in the control group. Upon univariate analysis, excess and absence of
      oxygenation treatment (OR = 9.18, CI = 1.13-74.86, P = 0.03) and anemia (OR =
      4.30, CI = 1.04-17.78, P = 0.04) were shown to be associated with contrast
      induced nephropathy incidence. Conclusion: Oxygenation, a simple,
      nonpharmacological strategy, may be beneficial when using contrast media in
      patients with impaired renal function from noninvasive angiography to emergency
      catheterization.

PMID- 29340316
TI  - NPT-IIb Inhibition Does Not Improve Hyperphosphatemia in CKD.
AB  - Introduction: Serum phosphate levels are insufficiently controlled in many
      patients with end-stage renal disease (ESRD), and novel therapeutic strategies
      are needed. Blocking intestinal phosphate absorption mediated by sodium-dependent
      phosphate co-transporter type 2b (NPT-IIb) holds promise; thus, we evaluated the
      efficacy, safety, tolerability, and pharmacokinetics of the novel and specific
      small molecule NPT-IIb inhibitor ASP3325 for the first time in humans. Methods:
      We conducted a randomized, double-blind, placebo-controlled, phase 1a single (n =
      88) and multiple (n = 36) ascending dose study in healthy subjects, and a
      randomized, open-label, uncontrolled, phase 1b study in hyperphosphatemic ESRD
      patients on hemodialysis (single oral dose, n = 5; multiple oral doses, n = 17).
      Primary efficacy measures were urinary phosphate and fecal phosphorous excretion
      (healthy subjects) and serum phosphate level (ESRD patients). Results: No time-
      or dose-dependent changes in urinary phosphate or fecal phosphorous excretion
      were observed following single/multiple ASP3325 doses for 7 days in healthy
      subjects. In ESRD patients, ASP3325 administered 3 times daily for 2 weeks before
      or after a meal did not reduce serum phosphate levels. ASP3325 was safe and well
      tolerated in both populations. Conclusion: NPT-IIb inhibition with ASP3325 was
      not effective in reducing serum phosphate levels in ESRD patients. The relevance
      of NPT-IIb in humans and feasibility of oral NPT-IIb inhibitors for treatment of
      hyperphosphatemia in ESRD remain uncertain.

PMID- 29340318
TI  - APOL1 Risk Variants Independently Associated With Early Cardiovascular Disease
      Death.
AB  - Introduction: The relationship of APOL1 renal risk variants to cardiovascular
      disease (CVD) is controversial and was the subject of this investigation.
      Methods: Age, cause of death, and nephrosclerosis (the latter defined by
      glomerulosclerosis) were analyzed in the autopsies of 162 African Americans and
      136 whites genotyped for APOL1 risk alleles. Results: Sudden deaths represented
      >75% of CVD autopsies for both races and all-risk genotypes. The average ages of
      CVD deaths for African Americans with 1 and 2 APOL1 risk alleles were,
      respectively, 7.0 years (P = 0.02) and 12.2 years (P < 0.01) younger than African
      Americans with 0 risk alleles and 8.7 years (P = 0.01) and 13.9 years (P = 0.01)
      younger than whites. Age differences were not significant between African
      Americans and whites with 0 risk alleles (P = 0.61). The younger CVD deaths of
      African Americans were associated with less severe glomerulosclerosis with 2 (P =
      0.01), although not 1 (P = 0.09), compared with 0 APOL1 risk alleles.
      Cardiomyopathy was found in 23% of African Americans with 1 and 2 risk alleles
      and significantly contributed to the lower age (P = 0.01). For non-CVD deaths,
      age differences were not seen by race (P = 0.28) or among African Americans by
      risk allele status (P = 0.38). Conclusion: Carriage of 1 or 2 APOL1 risk alleles
      in African Americans was associated with earlier age deaths due to coronary
      artery disease and cardiomyopathy. For 2 risk alleles, the early age was
      independent of nephrosclerosis.

PMID- 29340317
TI  - Intradialytic Cognitive and Exercise Training May Preserve Cognitive Function.
AB  - Introduction: Cognitive decline is common and increases mortality risk in
      hemodialysis patients. Intradialytic interventions like cognitive training (CT)
      and exercise training (ET) may preserve cognitive function. Methods: We conducted
      a pilot randomized controlled trial of 20 hemodialysis patients to study the
      impact of 3 months of intradialytic CT (tablet-based brain games) (n = 7), ET
      (foot peddlers) (n = 6), or standard of care (SC) (n = 7) on cognitive function.
      Global cognitive function was measured by the Modified Mini Mental Status Exam
      (3MS), psychomotor speed was measured by Trail Making Tests A and B (TMTA and
      TMTB), and executive function was assessed by subtracting (TMTB - TMTA). Lower
      3MS scores and slower TMTA and TMTB times reflected worse cognitive function. P
      values for differences were generated using analysis of variance, and 95%
      confidence intervals (CIs) and P values were generated from linear regression.
      Results: Patients with SC experienced a decrease in psychomotor speed and
      executive function by 3 months (TMTA: 15 seconds; P = 0.055; TMTB: 47.4 seconds;
      P = 0.006; TMTB - TMTA; 31.7 seconds; P = 0.052); this decline was not seen among
      those with CT or ET (all P > 0.05). Compared with SC, the difference in the mean
      change in 3MS score was -3.29 points (95% CI: -11.70 to 5.12; P = 0.42) for CT
      and 4.48 points (95% CI: -4.27 to 13.22; P = 0.30) for ET. Compared with SC, the
      difference in mean change for TMTA was -15.13 seconds (95% CI: -37.64 to 7.39; P
      = 0.17) for CT and -17.48 seconds (95% CI: -41.18 to 6.22; P = 0.14) for ET, for
      TMTB, the difference was -46.72 seconds (95% CI: -91.12 to -2.31; P = 0.04) for
      CT and -56.21 seconds (95% CI: -105.86 to -6.56; P = 0.03) for ET, and for TMTB -
      TMTA, the difference was -30.88 seconds (95% CI: -76.05 to 14.28; P = 0.16) for
      CT and -34.93 seconds (95% CI: -85.43 to 15.56; P = 0.16) for ET. Conclusion:
      Preliminary findings of our pilot study suggested that cognitive decline in
      psychomotor speed and executive function is possibly prevented by intradialytic
      CT and ET. These preliminary pilot findings should be replicated.

PMID- 29340319
TI  - Life Expectancy for Patients From the Southeastern United States With IgA
      Nephropathy.
AB  - Introduction: Although end-stage renal disease (ESRD) and surrogate markers for
      renal dysfunction are frequently used as outcome markers for IgA nephropathy, the
      clinical course after reaching ESRD is not well documented. This study examined
      outcomes of progression to ESRD and age at death in a cohort of adults with IgA
      nephropathy with a long duration of follow-up. Methods: Patient and kidney
      survival of 251 adult patients with IgA nephropathy from the southeastern United
      States diagnosed between January 1, 1976 and December 31, 2005 were analyzed.
      Results: Median age at diagnosis was 36.9 years. Most patients were men (69%) and
      Caucasian (95%). Only 46% had an estimated glomerular filtration rate >60 ml/min
      per 1.73 m2 at diagnosis. Mean follow-up time from time of diagnostic biopsy to
      death or end of study was 19.3 years. Of 251 patients, 132 (53%) progressed to
      ESRD and 97 (39%) died. Life expectancy was reduced by 10.1 years, with a median
      observed age of death at 65.7 years and a median expected age at death of 75.8
      years. Eighty-three percent of the deaths occurred after progression to ESRD.
      Conclusion: Life expectancy is substantially reduced for patients diagnosed with
      IgA nephropathy in the southeastern United States.

PMID- 29340320
TI  - Association of a Low-Protein Diet With Slower Progression of CKD.
AB  - Introduction: Reducing protein intake is recommended for slowing chronic kidney
      disease (CKD) progression, but assessment of its true effectiveness is sparse.
      Methods: Using the Maroni formula, we assessed dietary protein intake (DPI) from
      24-hour urinary urea excretion in 1594 patients (67% men and 33% women) with CKD,
      784 of whom also had 7-day food records. Cause-specific hazard ratios (HRs) and
      95% confidence intervals for the competing risks of DPI-associated end-stage
      renal disease (ESRD) or death were estimated in 1412 patients with baseline
      glomerular filtration rate >=15 ml/min per 1.73 m2, measured by 51Cr-EDTA renal
      clearance (mGFR). Results: Overall, mean DPI estimated from urea excretion was
      1.09 +/- 0.30 g/kg of body weight per day (range = 0.34-2.76); 20% of patients
      had values > 1.3 g/kg per day, and 1.9% had values < 0.6 g/kg per day. Urea
      excretion and food records produced similar estimates of mean DPI. The lower the
      mGFR, the lower the mean DPI. Over a median follow-up of 5.6 years, there were
      319 ESRD events and 189 pre-ESRD deaths. After adjusting for relevant covariates,
      each 0.1 g/kg daily higher baseline urea excretion-based DPI or food record-based
      DPI was associated with an HR for ESRD of 1.05 (95% confidence interval 1.01
      1.10) or 1.09 (95% confidence interval 1.04-1.14), respectively. HRs were
      stronger in patients with baseline mGFR < 30 ml/min per 1.73 m2. There was no
      association with mortality. The mean age of the patients was 59 +/- 15 years, and
      mean body mass index was 26.6 +/- 5.2 kg/m2. Conclusion: In this prospective
      observational study, the lower the baseline DPI, the slower the progression
      toward ESRD. Most importantly, the absence of threshold for the relation between
      DPI and ESRD risk indicates that there is no optimal DPI in the range observed in
      this cohort.

PMID- 29340321
TI  - Randomized Clinical Trial Design to Assess Abatacept in Resistant Nephrotic
      Syndrome.
AB  - Introduction: Treatment-resistant nephrotic syndrome is a rare form of glomerular
      disease that occurs in children and adults. No Food and Drug Administration
      approved treatments consistently achieve remission of proteinuria and
      preservation of kidney function. CD80 (B7-1) can be expressed on injured
      podocytes, and administration of abatacept (modified CTLA4-Ig based on a natural
      ligand to CD80) has been associated with sustained normalization of urinary
      protein excretion and maintenance of glomerular filtration rate in experimental
      and clinical settings. Methods: In this report, we describe the rationale for and
      design of a randomized, placebo-controlled, clinical trial of abatacept in
      patients with treatment-resistant nephrotic syndrome caused by focal segmental
      glomerulosclerosis or minimal change disease. The design is a hybrid of a
      parallel-group and crossover design (switchover) with the primary objectives
      assessed in the first period of the study and the secondary objectives assessed
      using data from both periods. All participants will receive the active agent in 1
      of the periods. The duration of treatment will be 4 months per period. Results:
      The primary outcome will be improvement in nephrotic-range proteinuria to
      subnephrotic range, that is, reduction from baseline to 4 months in urine
      protein:creatinine ratio >= 50% and to a level < 3. The projected sample size is
      90 patients, which has 80% power to detect a treatment difference of 28%.
      Conclusion: This study advances efforts to validate CD80 as a therapeutic target
      for treatment-resistant nephrotic syndrome, and implements a precision medicine
      based approach to this serious kidney condition in which the selection of a
      therapeutic agent is guided by the underlying disease mechanism operating in
      individual patients.

PMID- 29340322
TI  - Paricalcitol Versus Calcifediol for Treating Hyperparathyroidism in Kidney
      Transplant Recipients.
AB  - Introduction: Secondary hyperparathyroidism (SHPT) and vitamin D deficiency are
      common at kidney transplantation and are associated with some early and late
      complications. This study was designed to evaluate whether paricalcitol was more
      effective than nutritional vitamin D for controlling SHPT in de novo kidney
      allograft recipients. Methods: This was a 6-month, investigator-initiated,
      multicenter, open-label, randomized clinical trial. Patients with
      pretransplantation iPTH between 250 and 600 pg/ml and calcium <10 mg/dl were
      randomized to paricalcitol (PAR) or calcifediol (CAL). The intention-to-treat
      population (PAR: n = 46; CAL: n = 47) was used for the analysis. The primary
      endpoint was the percentage of patients with serum iPTH >110 pg/ml at 6 months.
      Secondary endpoints were bone mineral metabolism, renal function, and allograft
      protocol biopsies. Results: The primary outcome occurred in 19.6% of patients in
      the PAR group and 36.2% of patients in the CAL group (P = 0.07). However, there
      was a higher percentage of patients with iPTH <70 pg/ml in the PAR group than in
      the CAL group (63.4% vs. 37.2%; P = 0.03). No differences were observed in bone
      turnover biomarkers and bone mineral density. The estimated glomerular filtration
      rate was significantly higher in the CAL group than in the PAR group without
      differences in albuminuria. In protocol biopsies, interstitial fibrosis and
      tubular atrophy tended to be higher in the PAR group than in the CAL group (48%
      vs. 23.8%; P = 0.09). Both medications were well tolerated. Conclusion: Both PAR
      and CAL reduced iPTH, but PAR was associated with a higher proportion of patients
      with iPTH <70 pg/ml. These results do not support the use of PAR to treat
      posttransplantation hyperparathyroidism.

PMID- 29340323
TI  - Clinical and Pathological Significance of Autoantibodies to Erythropoietin
      Receptor in Type 2 Diabetic Patients With CKD.
AB  - Introduction: We examined the impact of autoantibodies on the erythropoietin
      receptor (EPOR) in type 2 diabetic patients with chronic kidney disease (CKD).
      Methods: A total of 112 Japanese patients with type 2 diabetes who had CKD were
      enrolled in this study and followed for a mean of 45 months. Sera from these
      patients were screened for anti-EPOR antibodies using enzyme-linked immunosorbent
      assays. Results: Anti-EPOR antibodies were detected in 26 patients (23%). Anti
      EPOR antibodies were associated with low hemoglobin concentrations and decreased
      renal function. In patients with biopsy-proven diabetic nephropathy, anti-EPOR
      antibodies were associated with increased levels of interstitial inflammation. A
      decrease in renal function was observed more frequently in patients with
      antibodies than in those without antibodies, and the presence of the antibodies
      together with well-known clinical parameters, including proteinuria and low
      glomerular filtration rate, was a significant risk factor for end-stage renal
      disease. In human tubular epithelial HK-2 cells, IgG fractions containing anti
      EPOR antibodies upregulated the expression of monocyte chemoattractant protein-1
      mRNA under a high concentration of glucose. Conclusion: Anti-EPOR antibodies
      might be involved in the progression of renal lesions and in the impaired
      erythropoiesis in type 2 diabetic patients with CKD. Furthermore, the presence of
      anti-EPOR antibodies may be an additional predictor for end-stage renal disease
      in type 2 diabetes.

PMID- 29340324
TI  - Temporal Association Between PLA2R Antibodies and Clinical Outcomes in Primary
      Membranous Nephropathy.
AB  - Introduction: Autoantibodies to M-type phospholipase A2 receptor (aPLA2R) are
      seen in two-thirds of patients with primary membranous nephropathy (PMN) and are
      associated with disease activity. However, the precise temporal dynamics between
      the presence and amount of aPLA2R in circulation, as well as the clinical
      activity, are not known. We evaluated the temporal association between disease
      activity and serum aPLA2R during and after treatment in PMN. Methods: The study
      included all patients with PMN and elevated aPLA2R who were started on
      immunosuppressive therapy for persistent nephrotic syndrome at a single center
      between December 2014 and December 2015. Serum samples were tested for aPLA2R at
      baseline and at monthly intervals for 6 months. Clinical details were collected
      monthly for 9 months. Serological remission was defined as negative aPLA2R in 2
      consecutive samples. Clinical remission was defined by standard criteria.
      Results: A total of 30 patients with PMN were studied. Of these, 28 (93%) had
      elevated levels at baseline, whereas 2 (7%) became positive after 1 month. The
      mean age was 33.2 +/- 1 (range, 13-52) years. Median baseline aPLA2R titer was
      163.41 (range, 70-291.01) RU/ml. A total of 24 patients (80%) achieved
      serological remission by 6 months. Among all the serological responders, 54% had
      achieved negative aPLA2R by the end of the first month. Clinical remission was
      observed in 20 patients (67%). Serological and clinical remission were noted at
      2.7 +/- 1.71 and 5.05 +/- 2.64 months, respectively. Conclusion: In patients with
      aPLA2R-associated PMN, reduction in circulating aPLA2R precedes clinical
      remission. Persistence of aPLA2R at the end of therapy is associated with
      clinical resistance.

PMID- 29340325
TI  - End-Stage Kidney Disease From Scleroderma in the United States, 1996 to 2012.
AB  - Introduction: Although the management of scleroderma continues to evolve, it is
      unknown whether the burden of end-stage kidney disease (ESKD) treated with
      maintenance renal replacement therapy from SD has changed. Methods: We examined
      United States Renal Data System data (n = 1,677,303) for the years 1996 to 2012
      to quantify the incidence and outcomes of ESKD from scleroderma treated with
      renal replacement therapy (n = 2398). Outcomes assessed through demography
      matched scleroderma-positive/scleroderma-negative comparisons included recovery
      of kidney function, mortality, listing for transplant, renal transplantations,
      and graft failure. Results: Overall ESKD rates from scleroderma were 0.5 per
      million per year. Adjusted incidence ratios fell over time, to 0.42 in 2012 (vs.
      1996, 95% confidence interval [CI] = 0.32-0.54, P < 0.001). Adjusted incidence
      ratios for ESKD from scleroderma fell over time in both sexes, all age, race, and
      ethnicity categories except age < 20 years and Asian race, and in all regions of
      the United States. After initiating renal replacement therapy, patients with
      scleroderma had a greater likelihood of recovery of kidney function (hazards
      ratio [HR] = 2.67, 95% CI = 1.90-3.76, P < 0.001) and death (HR = 1.44, 95% CI =
      1.34-1.54, P < 0.001) and a lower likelihood of transplantation (HR = 0.51, 95%
      CI = 0.44-0.59, P < 0.001) than demography-matched patients without scleroderma.
      Conclusion: The incidence of ESKD from scleroderma appears to have declined in
      the United States since 1996. ESKD from scleroderma is associated with an
      enhanced likelihood of recovery of kidney function and death, a reduced
      likelihood of transplantation, and similar outcomes after transplantation.

PMID- 29340326
TI  - mTORC1 Inhibition Is an Effective Treatment for Sporadic Renal Angiomyolipoma.
AB  - Introduction: Renal angiomyolipoma (AML) is the most common benign renal tumor.
      Despite a generally benign histology, AML can result in significant morbidity,
      from intra-abdominal hemorrhage and reduction in kidney function. While
      classically associated with the autosomal dominant disorder tuberous sclerosis
      complex (TSC) or with pulmonary lymphangioleiomyomatosis, most AMLs are sporadic.
      Mammalian target of rapamycin complex 1 (mTORC1) inhibitors (e.g., sirolimus)
      have been found to be effective in treating TSC- or lymphangioleiomyomatosis
      associated AML, but to date it is unknown whether this strategy is effective for
      sporadic AML. Methods: We stained tumor specimens of sporadic AML patients for
      pS6 to assess for mTORC1 activation. Results: We detected strong activation of
      the mTORC1 pathway, similar to TSC-associated AML. Consequently, we showed that
      in vitro treatment with sirolimus results in significant growth inhibition of the
      human sporadic AML cell line SV7Tert, similar to the effect seen when the same
      treatment is applied to the human TSC-associated AML cell line UMBSV-tel. To
      further investigate the potential of mTORC1 inhibition for treating sporadic AML
      and assess whether the in vitro results are clinically relevant, we identified a
      patient with sporadic, bilateral AMLs, showing continued tumor growth following a
      partial nephrectomy. Using immunostaining, we detected strong mTORC1 activation
      in the patient's AML tissue. Accordingly, upon treatment with sirolimus, we noted
      significant reduction in the patient's tumor volume and resolution of
      hydronephrosis, without any significant side effects. Conclusion: We propose
      mTORC1 inhibition as an effective treatment option for patients with sporadic
      AML, which represents the vast majority of patients with this tumor.

PMID- 29340327
TI  - Trimethoprim+Sulfamethoxazole Reduces Rates of Melioidosis in High-Risk
      Hemodialysis Patients.
AB  - Introduction: Melioidosis causes sepsis and death in the Top End of Northern
      Australia during the monsoonal wet season. Dialysis-dependent adults suffer
      higher melioidosis rates compared to low rates among renal transplant patients
      who routinely receive trimethoprim+sulfamethoxazole prophylaxis. Methods: We
      performed a prospective interventional study to determine the efficacy and safety
      of daily trimethoprim+sulfamethoxazole prophylaxis in hemodialysis patients
      during the wet season, from 1 November 2014 to 30 April 2015. Hemodialysis (for
      >= 3 months) patients >= 18 years of age were offered treatment. A total of 269
      patients on hemodialysis were eligible. Eight of the 269 patients (3%) were
      excluded from the analysis for being on melioidosis treatment. In all, 169 of 261
      patients (64.8%) received the prophylaxis, and 92 of 261 patients (35.2%) did
      not, because of allergy history (n = 10), remoteness and logistical reasons (n =
      60), poor dialysis attendance (n = 11), and refusal (n = 11). We monitored for
      clinical side effects 3 times weekly and neutropenia, thrombocytopenia, and liver
      function monthly throughout treatment and for 2 months posttreatment. Results: In
      all, 169 of 261 patients (64.8%) received the prophylaxis. There was no age
      (years) difference by group (prophylaxis vs. nonprophylaxis, 54.7 [11.3] vs. 54.3
      [11.2] [P = 0.751]). Sixteen of 261 patients (6%) had melioidosis. The event
      frequency was 0% (0/169, prophylaxis, vs. 17.4% [16/92, nonprophylaxis], P <
      0.001). Higher thrombocytopenia and neutropenia rates were noted in the
      prophylaxis group. These did not warrant treatment stoppage. There was no
      difference in liver function. Three patients (1.8%) withdrew from the treatment
      because of side effects. Conclusion: Daily dosing was effective and safe.
      Posthemodialysis dosing in the subsequent seasons was effective and safer. We
      recommend this approach in melioidosis-prevalent regions.

PMID- 29340328
TI  - Nephrin Loss Can Be Used to Predict Remission and Long-term Renal Outcome in
      Patients With Minimal Change Disease.
AB  - Introduction: Minimal change disease is a common cause of nephrotic syndrome. In
      general, patients with minimal change disease respond to corticosteroids and have
      excellent long-term renal survival. However, some patients have less favorable
      outcome. These patients are often thought to have progressed to focal segmental
      glomerulosclerosis. We previously reported that a segmental loss of podocyte
      markers is present before the development of focal segmental glomerulosclerosis
      in a rat model. Here, we investigated whether loss of podocyte marker nephrin can
      serve as a biomarker for predicting poor outcome in patients with minimal change
      disease. Methods: We obtained 47 kidney biopsy samples from patients diagnosed
      with minimal change disease and stained sections with periodic acid-Schiff and
      for nephrin. Nephrin loss was scored by 2 independent researchers who were
      blinded to clinical outcome. Clinical data were collected retrospectively, and
      nephrin loss was correlated with clinical follow-up data. Results: Nephrin loss
      was present in 34% of the biopsy samples. During follow-up, patients with nephrin
      loss achieved remission less frequently (61%) compared to patients without (96%)
      (P = 0.002). Moreover, 5-year eGFR was lower in the patients with renal nephrin
      loss. The risk of eGFR decreasing to < 60 ml/min per 1.73m2 increased with each
      percentage of glomeruli with nephrin loss (hazard ratio = 1.044, 95% confidence
      interval = 1.02-1.07). Conclusion: These results indicate that nephrin loss in
      patients with minimal change disease can help predict both remission and long
      term renal outcome.

PMID- 29340329
TI  - A Salivary Urea Nitrogen Dipstick to Detect Obstetric-Related Acute Kidney
      Disease in Malawi.
AB  - Introduction: Obstetric-related acute kidney injury (AKI) is associated with
      adverse outcomes for mother and fetus, particularly in low-income countries.
      However, laboratory-independent tools to facilitate diagnosis are lacking. We
      assessed the diagnostic performance of a salivary urea nitrogen (SUN) dipstick to
      detect obstetric-related acute kidney disease in Malawi. Methods: Women at high
      risk for AKI admitted to an obstetric unit in Blantyre, Malawi, were recruited
      between 21 September and 11 December 2015. Patients underwent serum creatinine
      (SCr) testing alongside measurement of SUN using a dipstick on admission, and
      every 48 hours thereafter if evidence of kidney disease was found. Results: A
      total of 301 patients were included (mean age 25.9 years, 11% HIV positive). Of
      the patients, 23 (7.6%) had AKI, stage 1 in 47.8%, most commonly due to
      preeclampsia/eclampsia. Mean presenting SCr values were 108.8 +/- 21.8 MUmol/l
      (1.23 +/- 0.25 mg/dl), 118 +/- 34.45 MUmol/l (1.33 +/- 0.39 mg/dl), and 136.1 +/-
      30.4 MUmol/l (1.54 +/- 0.34 mg/dl) in AKI stages 1 to 3 respectively. SUN > 14
      mg/dl had a sensitivity of 12.82% and a specificity of 97.33% to detect acute
      kidney disease; the area under the receiver operating characteristic curve was
      0.551. In patients with normal SUN on admission, perinatal mortality was 11.8%,
      and was 25.0% if SUN was > 14 mg/dl (P = 0.18). Conclusion: The SUN dipstick was
      specific but insensitive when used to diagnose obstetric-related AKI. Limited
      biochemical derangement and low salivary urea concentrations due to physiological
      changes in pregnancy, as opposed to a technical limitation of the dipstick
      itself, are the likely reason for the lack of sensitivity in this study.

PMID- 29340330
TI  - Efficacy and Safety of Sucroferric Oxyhydroxide and Calcium Carbonate in
      Hemodialysis Patients.
AB  - Introduction: In this phase III, open-label, single-arm, multi-center 12-week
      study, we evaluated the efficacy and safety of combination therapy with
      sucroferric oxyhydroxide (PA21) and calcium carbonate for hemodialysis patients
      with hyperphosphatemia. Methods: We enrolled 35 subjects aged >= 20 years with
      end-stage kidney disease and serum phosphorus 3.5-6.0 mg/dl who were undergoing
      hemodialysis 3 times weekly and taking calcium carbonate and sevelamer
      hydrochloride. Patients switched from sevelamer hydrochloride and calcium
      carbonate to sucroferric oxyhydroxide and calcium carbonate. Sucroferric
      oxyhydroxide was orally administered 3 times daily within 750 mg/d (250 mg per
      dose) to 3000 mg/d (1000 mg per dose), immediately before every meal, for 12
      weeks. Calcium carbonate was orally administered 3 times daily after every meal.
      Outcomes were serum phosphorus concentration, safety, and satisfaction with bowel
      movements. Results: Mean (SD) serum phosphorus concentrations were 5.01 (0.63)
      mg/dl at week 0 and 4.89 (1.14) mg/dl at the end of treatment, after patients
      switched from sevelamer hydrochloride to sucroferric oxyhydroxide. The incidence
      of adverse drug reactions was 31.4% (11/35), with diarrhea being the most
      frequent (31.4%). More sucroferric oxyhydroxide-treated patients were satisfied
      with their bowel movements. More patients with constipation, as well as those who
      experienced diarrhea, were satisfied with their bowel movements at the end of the
      study. Conclusion: Combined administration of sucroferric oxyhydroxide and
      calcium carbonate at low doses was effective in maintaining serum phosphorus
      concentrations within the target range, and patients' gastrointestinal status
      improved. Sucroferric oxyhydroxide maintained its serum phosphorus-lowering
      effect with a decreased pill burden, and its concomitant administration with
      calcium carbonate was well tolerated.

PMID- 29340331
TI  - Location-Specific Oral Microbiome Possesses Features Associated With CKD.
AB  - Introduction: Chronic kidney disease (CKD), a progressive loss of renal function,
      can lead to serious complications if underdiagnosed. Many studies suggest that
      the oral microbiota plays important role in the health of the host; however,
      little is known about the association between the oral microbiota and CKD
      pathogenesis. Methods: In this study, we surveyed the oral microbiota in saliva,
      the left and right molars, and the anterior mandibular lingual area from 77
      participants (18 with and 59 without CKD), and tested their association with CKD
      to identify microbial features that may be predictive of CKD status. Results: The
      overall oral microbiota composition significantly differed by oral locations and
      was associated with CKD status in saliva and anterior mandibular lingual samples.
      In CKD patients, we observed a significant enrichment of Neisseria and depletion
      of Veillonella in both sample types and a lower prevalence of Streptococcus in
      saliva after adjustment for other comorbidities. Furthermore, we detected a
      negative association of Neisseria and Streptococcus genera with the kidney
      function as measured by estimated glomerular filtration rate. Neisseria abundance
      also correlated with plasma interleukin-18 levels. Conclusion: We demonstrate the
      association of the oral microbiome with CKD and inflammatory kidney biomarkers,
      highlighting a potential role of the commensal bacteria in CKD pathogenesis. A
      better understanding of the interplay between the oral microbiota and CKD may
      help in the development of new strategies to identify at-risk individuals or to
      serve as a novel target for therapeutic intervention.

PMID- 29340332
TI  - Endothelial Progenitor Cells and Vascular Health in Dialysis Patients.

PMID- 29340333
TI  - Acute Kidney Injury Ascertainment Is Affected by the Use of First Inpatient
      Versus Outpatient Baseline Serum Creatinine.

PMID- 29340334
TI  - The Authors Reply.

PMID- 29340335
TI  - Dialysis Should Be Started When Absolutely Necessary, Not Early and
      Incrementally.

PMID- 29340336
TI  - Re: Further Evidence Supporting the Accuracy of Quantitative Magnetic Resonance
      Imaging for Evaluating Iron Load in Dialysis Patients.

PMID- 29340337
TI  - The Author Replies.

PMID- 29340338
TI  - The Author Replies.

PMID- 29340339
TI  - Other Estimation of Blood Losses in Hemodialysis and Formula for Translating
      Liver Iron Concentration From Iron Balance Calculation Based on Iron Removal by
      Phlebotomy.

PMID- 29340340
TI  - American Geriatrics Society Beers Criteria and Anticoagulant Use in Older Adults
      With Renal Impairment.

PMID- 29340341
TI  - Credentialing of Hospitalists in Ultrasound-Guided Bedside Procedures: A Position
      Statement of the Society of Hospital Medicine.
AB  - Ultrasound guidance is used increasingly to perform the following 6 bedside
      procedures that are core competencies of hospitalists: abdominal paracentesis,
      arterial catheter placement, arthrocentesis, central venous catheter placement,
      lumbar puncture, and thoracentesis. Yet most hospitalists have not been certified
      to perform these procedures, whether using ultrasound guidance or not, by
      specialty boards or other institutions extramural to their own hospitals.
      Instead, hospital privileging committees often ask hospitalist group leaders to
      make ad hoc intramural certification assessments as part of credentialing. Given
      variation in training and experience, such assessments are not straightforward
      "sign offs." We thus convened a panel of experts to conduct a systematic review
      to provide recommendations for credentialing hospitalist physicians in ultrasound
      guidance of these 6 bedside procedures. Pathways for initial and ongoing
      credentialing are proposed. A guiding principle of both is that certification
      assessments for basic competence are best made through direct observation of
      performance on actual patients.

PMID- 29340342
TI  - Precision of the Connection Between Implant and Standard or Computer-Aided
      Design/Computer-Aided Manufacturing Abutments: A Novel Evaluation Method.
AB  - PURPOSE: The aim of this in vitro study was to verify whether or not stock and
      computer-aided design/computer-aided manufacturing (CAD/CAM) abutments show
      similar precision in the connection with the respective implants. MATERIALS AND
      METHODS: Ten CAD/CAM titanium abutments were compared with 10 stock titanium
      abutments. Each abutment fit a regular-platform implant (Institute Straumann).
      Implants and abutments were measured independently and then connected. During the
      connection procedure, the torque was measured using a six-axes load cell. Then,
      outer geometric features of the implant-abutment connection were measured again.
      Finally, the assembly was sectioned to provide the analysis of inner surfaces in
      contact. The geometric measurements were performed using a multisensored opto
      mechanical coordinate measuring machine. The following parameters were measured
      and compared for the CAD/CAM and stock titanium abutment groups, respectively:
      width of interference and interference length between the conical surfaces of the
      implant and abutment; and volume of material involved in the implant-abutment
      connection. RESULTS: Interference width mean +/- SD values of 18 +/- 0.5 and 14
      MU 0.5 MUm were calculated for the stock and CAD/CAM titanium abutment groups,
      respectively. The difference was statistically significant (P = .02).
      Furthermore, the interference length mean +/- SD values of 763 +/- 10 and 816 +/-
      43 MUm were calculated for stock and CAD/CAM titanium abutment groups,
      respectively. The difference was also statistically significant (P = .04).
      Finally, the volume of material involved in the implant-abutment connection was
      compared between stock and CAD/CAM titanium abutment groups; the mean +/- SD
      values of 0.134 +/- 0.014 and 0.108 +/- 0.023 mm3 were significantly different (P
      = .009). CONCLUSION: Both standard and CAD/CAM abutment groups showed a three
      dimensional (3D) seal activation after the screw tightening. Nevertheless, stock
      titanium abutments showed a significantly higher volume of material involved in
      the implant-abutment connection compared with that of CAD/CAM titanium abutments.

PMID- 29340343
TI  - What is the Impact of Epstein-Barr Virus in Peri-implant Infection?
AB  - PURPOSE: To compare the qualitative and quantitative profile of Epstein-Barr
      virus (EBV) at external and internal implant surfaces between participants with
      peri-implantitis and healthy peri-implant tissues and to quantitatively assess
      the relation between EBV and periopathogens inside the microbiologic profile
      associated with peri-implantitis. MATERIALS AND METHODS: Microbiologic specimens
      were retrieved from 84 patients wearing 190 implants to estimate the levels of
      EBV and 10 periopathogens in the peri-implant pocket and internal-implant
      connection using quantitative polymerase chain reaction. RESULTS: The study
      sample consisted of 113 healthy and 77 peri-implantitis-affected implants.
      Statistical significance was not reached in EBV prevalence between peri
      implantitis and healthy controls. EBV-positive participants demonstrated higher
      levels of Prevotella intermedia (Pi) and Campylobacter rectus (Cr) compared with
      EBV-negative participants. A positive correlation was demonstrated among EBV and
      Tannerella forsythia (Tf), Parvimonas micra (Pm), Fusobacterium nucleatum (Fn),
      and Cr levels in peri-implantitis-affected implants, while healthy controls
      demonstrated a positive correlation between EBV and Aggregatibacter
      actinomycetemcomitans (Aa), Pi, and Pm. CONCLUSION: EBV cannot be considered as a
      microbiologic marker of peri-implantitis. However, EBV could be considered as a
      risk factor and a peri-implantitis enhancer based on its positive correlations
      with pathogens associated with peri-implantitis.

PMID- 29340344
TI  - Biomechanical Comparison of Different Implant Inclinations and Cantilever Lengths
      in All-on-4 Treatment Concept by Three-Dimensional Finite Element Analysis.
AB  - PURPOSE: The aim of this study was to evaluate the effect of implant inclination
      and cantilever length on the stress distribution in mandibular cortical bone,
      implant, abutment, prosthetic framework, and prosthetic screw via three
      dimensional (3D) finite element analysis (FEA). MATERIALS AND METHODS: Four
      different finite element models (0-0, 17-17, 30-30, 45-30) were designed
      according to the tilting angle (0, 17, 30, and 45 degrees) of the posterior
      implant and angle of multiunit abutments (0, 17, and 30 degrees). Screw-retained
      fixed prostheses with different cantilever lengths in accordance with implant
      inclination were modeled. A foodstuff was used for the 100-N load application.
      Maximum principal (Pmax) and minimum principal (Pmin) stresses were calculated
      for cortical bone, and von Mises stress values were calculated for the implant,
      abutment, metal framework, and prosthetic screw. RESULTS: The highest stress
      values were observed in the anterior implant, surrounding bone, and prosthetic
      components of the 0-0 configuration. Pmin stress values in bone were gradually
      decreased with the increasing inclination of both anterior and posterior
      implants. Peak Pmax stress values were detected in the 0-0 group. For the
      cortical bone around the posterior implant, the 30-30 group showed the lowest
      Pmax value. The highest von Mises stress on implants was found at the posterior
      implant of the 30-30 group. The stress values on abutments gradually decreased
      with the increase of the angulation of the posterior implants. For prosthetic
      screws, the 30-30 and 45-30 groups exhibited lower stress values, and for the
      metal framework, the 30-30 group exhibited lower stress values. CONCLUSION:
      Biomechanical comparison via 3D FEA revealed that decreasing the cantilever
      length by tilting the posterior implants resulted in a reduction in stress values
      in the peri-implant bone, abutment, prosthetic screw, and metal framework. The
      groups with 30- and 45-degree tilted posterior implants and shorter cantilever
      lengths showed better stress distributions in comparison to the straight and 17
      degree tilted groups.

PMID- 29340345
TI  - Intraosseous Temperature Changes During Implant Site Preparation: In Vitro
      Comparison of Thermocouples and Infrared Thermography.
AB  - PURPOSE: Implant-supported dental prostheses are based on the principle of
      osseointegration, and the success of dental implantation depends on adequate
      formation of this intimate bone-to-implant contact. The application of heat
      during the drilling procedure leads to a rise in intraosseous temperature at the
      prospective implant site, which may result in various complications. The purpose
      of the present study was to compare the ability of thermocouples and infrared
      thermography to detect changes in intraosseous temperature during dental implant
      site preparation. MATERIALS AND METHODS: Standardized bovine costae bone blocks
      were used to simulate the cortical bone of the human mandible. Steel implant form
      drills with a diameter of 3.0 mm were used. Two types of irrigation systems were
      used (external cooling only and combined internal and external cooling). Drilling
      was performed at a constant speed (1,200 rpm). Changes in intraosseous
      temperature were evaluated using Type T Cu-CuNi thermocouples and an infrared
      thermography camera system at contact pressures of 5 and 20 N. RESULTS: Infrared
      thermography detected significantly greater increases in intraosseous temperature
      (DeltaT) than thermocouples for all tested combinations of cooling system and
      contact pressure (P <= .0001). CONCLUSION: These results suggest that
      thermography more accurately reflects intraosseous temperature changes during
      implant site preparation than thermocouples.

PMID- 29340346
TI  - Effects of Local Drug and Chemical Compound Delivery on Bone Regeneration Around
      Dental Implants in Animal Models: A Systematic Review and Meta-Analysis.
AB  - PURPOSE: One of the suggested methods for enhancing osseointegration is the local
      application of drug agents around implant surfaces. The aim of this review was to
      evaluate the methods most commonly used for local drug and chemical compound
      delivery to implant sites and assess their influence on osseointegration.
      MATERIALS AND METHODS: An electronic search was undertaken in three databases
      (PubMed, Scopus, Embase). The search was limited to animal experiments using
      endosseous implants combined with local drug delivery systems. Meta-analyses were
      performed for the outcome bone-to-implant contact (BIC). RESULTS: Sixty-one
      studies met the inclusion criteria. Calcium phosphate (CaP), bisphosphonates
      (BPs), and bone morphogenetic proteins (BMPs) were the most commonly used
      chemical compounds. There were two main methods for local drug delivery at the
      bone-implant interface: (1) directly from an implant surface by coating or
      immobilizing techniques, and (2) the local application of drugs to the implant
      site, using carriers. There was a statistically significant increase in BIC for
      both local drug delivery methods (P = .02 and P < .0001, respectively) compared
      with the control methods. There was a statistically significant increase in BIC
      when CaP (P = .0001) and BMPs (P = .02) were either coating implants or were
      delivered to the implant site, in comparison to when drugs were not used. The
      difference was not significant for the use of BPs (P = .15). CONCLUSION: It is
      suggested that the use of local chemical compound delivery systems around
      implants could significantly improve implant osseointegration in animal models.
      It is a matter of debate whether these in vivo results might have some
      significant effect in the human clinical setting in the long term.

PMID- 29340347
TI  - Effect of Attachment Type on Denture Strain in Maxillary Implant Overdentures:
      Part 2. Palateless Overdentures.
AB  - PURPOSE: The aim of this study was to examine the deformation modality of
      palateless maxillary implant overdentures using isolated attachments under
      various implant configurations. MATERIALS AND METHODS: A maxillary edentulous
      model with implants inserted in the anterior, premolar, and molar areas was
      fabricated, and three types of unsplinted attachments-ball, locator, and magnet
      were set on the implants distributed in various configurations. Experimental
      palateless dentures were fabricated, and two strain gauges were attached at the
      anterior midline of the labial and palatal sides. A vertical occlusal load of 98
      N was applied, and the shear strains of dentures were measured. The measurements
      of strains were compared with the Kruskal-Wallis test (P = .05). RESULTS: The
      strains of the labial side were much larger than those of the palatal side except
      for those using the ball attachment. The strains using the magnet attachment on
      anterior implants were significantly larger than those using other attachments (P
      < .05). Those using anterior implants were significantly smaller than those using
      premolar or molar implants (P < .05). CONCLUSION: The strains of palateless
      overdentures were different according to the attachments and implant
      distribution. However, when using molar implants, there was no significant
      difference among the three attachments.

PMID- 29340348
TI  - Peri-implant Tissues and Patient Satisfaction After Treatment of Vertically
      Augmented Atrophic Posterior Mandibles with Intraoral Onlay Block Bone Grafts: A
      Retrospective 3-Year Case Series Follow-up Study.
AB  - PURPOSE: To evaluate the peri-implant soft and hard tissues of dental implants
      placed in vertically regenerated posterior mandibles with intraoral onlay block
      bone grafts and patient satisfaction at 3-year follow-up. MATERIALS AND METHODS:
      A retrospective study of patients with dental implants placed in posterior
      mandibular sites vertically augmented with intraoral onlay block bone grafts was
      carried out between 2005 and 2009 at the University of Valencia. The outcomes
      assessed at the 3-year follow-up visit were the peri-implant soft tissues (Plaque
      Index and Bleeding Index, probing depth, keratinized mucosa width, and
      recession), implant survival and success rates, marginal bone loss, and patient
      satisfaction. RESULTS: Sixteen patients with 36 implants were included. The mean
      Plaque Index and Bleeding Index scores were <= 0.4. The mean band of facial
      keratinized mucosa was >= 3 mm in 52.7% of implants; 38.8% of the implants showed
      facial recession. The mean midfacial recession was -0.31 +/- 0.75 mm. Implant
      survival reached 100%, while the success rate was 85%, and the mean marginal bone
      loss was 1 +/- 1.03 mm (range: 0.1 to 5.3). Good quality of life (9.19 +/- 0.40)
      was reported for all patients, and the overall general satisfaction score was
      8.07 +/- 1.04 (mucosa esthetics: 7.71 +/- 1.45; prosthesis esthetics: 8.42 +/-
      0.6; chewing: 8.68 +/- 0.94; ease of cleaning: 8.01 +/- 1.03). CONCLUSION:
      Considering the limitations of the study, implants in vertically augmented
      posterior mandibular areas with intraoral onlay block bone grafts showed good
      soft tissue levels and high patient satisfaction. No implants were lost at 3
      years postloading, though one-fifth of the patients showed a statistically
      significant marginal bone loss.

PMID- 29340349
TI  - Prevalence of Dental Implants and Evaluation of Peri-implant Bone Levels in
      Patients Presenting to a Dental School: A Radiographic Cross-Sectional 2-Year
      Study.
AB  - PURPOSE: To evaluate the number of patients with dental implants who present to a
      dental school clinic for screening and to report the prevalence of peri-implant
      bone level change detected on digital panoramic radiographs of those subjects.
      MATERIALS AND METHODS: Patient screening files for 9,422 patients over a 2-year
      period were examined to see how many patients presented with dental implants.
      Those patients with at least one implant were further evaluated by measuring the
      bone level on the mesial and distal sides of the implant using the screening
      radiograph. RESULTS: A total of 187 patients (2%) had at least one implant. In
      regard to implants, 423 were examined and 146 (33%) had no detectable bone loss
      defined as bone level below the top of the implant. When thresholds of bone loss
      were evaluated, 109 implants (25%) had >= 2 mm of bone loss on either the mesial
      or distal sides or both. The median bone loss was 1.74 mm for the 277 implants
      with detectable bone loss and 2.97 mm for the 109 implants that had >= 2 mm bone
      loss. Interestingly, patients who were >= 70 years of age had significantly (P =
      .03) more bone loss in the mandible compared with the maxilla, while patients who
      were 60 to 69 years of age had significantly greater loss in the maxilla.
      CONCLUSION: These data reveal that for patients presenting to the dental school
      for a screening over a 2-year period, 1.98% had one or more dental implants.
      Furthermore, those patients with implants had a minimum amount of bone loss as
      measured from the top of the implant.

PMID- 29340350
TI  - Estimating the Importance of Significant Risk Factors for Early Dental Implant
      Failure: A Monte Carlo Simulation.
AB  - PURPOSE: The purpose of this study was to develop a probabilistic estimation of
      the strength of risk factors associated with early dental implant failure and
      rank them by importance. MATERIALS AND METHODS: A systematic literature search
      was performed on PubMed, Web of Knowledge, Scopus, Cochrane Central Register of
      Controlled Trials, and grey literature up to April 2017. A total of 368 records
      were identified. Following the removal of duplicate and irrelevant records, 56
      were screened. Eight studies met the inclusion criteria, in which seven
      statistically significant risk factors for early failure were selected and used
      to build a conceptual simulation model. Selected risk factors were, namely, "male
      sex," "smoking," "bone quality," "short implants," "wide implants," "adjacent
      teeth," and "periodontitis." Monte Carlo simulation with 100,000 iterations and a
      sensitivity analysis were performed to evaluate the risk estimates of these risk
      factors and to identify which of the risk factors are more important in
      influencing the model, respectively. RESULTS: The performed simulation model has
      shown a significant difference in terms of estimated effects of the risk factors
      on early failure rate. As a result, the most sensitive risk factor was found to
      be "periodontitis" with the second being "adjacent teeth" and the third
      "smoking." The least sensitive factor for early failure was "wide implants."
      CONCLUSION: This study develops a better understanding of the importance of risk
      factors for early dental implant failure by an estimated ranking.

PMID- 29340351
TI  - Effect of Low-Level Laser on the Healing of Bone Defects Filled with Autogenous
      Bone or Bioactive Glass: In Vivo Study.
AB  - PURPOSE: This study evaluated the effect of low-level laser therapy (LLLT) on the
      healing of bone defects filled with autogenous bone or bioactive glass. MATERIALS
      AND METHODS: A critical size defect with 5-mm diameter was created on the
      calvaria of 60 adult male rats divided into 6 groups (n = 10): group C (control),
      group LLLT (LLLT - GaAlAs, wavelength of 780 nm, power of 100 mW, energy density
      of 210 J/cm2 per point during 60 seconds/point, in five points, only once, after
      creation of the surgical defect), group AB (autogenous bone), group AB+LLLT
      (autogenous bone + LLLT), group BG (bioactive glass), group BG+LLLT (bioactive
      glass + LLLT). All animals were sacrificed at 30 days after surgery. The areas of
      newly formed bone (ANFB) and areas of remaining particles (ARP) were calculated
      in relation to the total area (TA). RESULTS: The highest mean +/- SD ANFB was
      observed for group LLLT (47.67% +/- 8.66%), followed by groups AB+LLLT (30.98% +/
      16.59%) and BG+LLLT (31.13% +/- 16.98%). There was a statistically significant
      difference in relation to ANFB between group C and the other groups, except for
      comparison with group BG (Tukey test, P > .05). There was no statistically
      significant difference in ANFB values between group AB and the other study groups
      (Tukey test, P > .05), group AB+LLLT and groups BG and BG+LLLT (Tukey test, P >
      .05), and between groups BG and BG+LLLT (Tukey test, P > .05). The highest mean
      +/- SD ARP was found for group BG (25.15% +/- 4.82%), followed by group BG+LLLT
      (17.06% +/- 9.01%), and there was no significant difference between groups (t
      test, P > .05). CONCLUSION: The LLLT, in the present application protocol, did
      not increase the area of new bone formation when associated with autogenous bone
      or bioactive glass.

PMID- 29340352
TI  - Bone Healing at Functionally Loaded and Unloaded Screw-Shaped Implants Supporting
      Single Crowns: A Histomorphometric Study in Humans.
AB  - PURPOSE: To evaluate histologically and histomorphometrically the effect of a
      delayed load on healing at implants with a moderately rough surface. MATERIALS
      AND METHODS: Two solid titanium screw-shaped devices, 5 mm long and 3.5 mm in
      diameter, were inserted in the distal segments of the alveolar ridge of 16
      volunteer patients in a nonsubmerged fashion. After 2 months, one implant was
      loaded, while the other was left unloaded. After 2 months, the two implants were
      collected from 10 patients using a sonic instrument, and ground sections were
      prepared from the biopsy specimens. Histomorphometric analyses were performed.
      RESULTS: After 4 months of healing, biopsy specimens from 10 patients were
      available for analyses (n = 10). The total bone-to-implant contact percentage was
      86.8% +/- 6.5% and 84.6% +/- 3.7% for loaded and unloaded implants, respectively.
      New bone was represented by 85.5% +/- 6.7% and 83.4% +/- 3.9% at the loaded and
      unloaded sites, respectively. A very small amount of old parent bone was found.
      The density of the mineralized bone was 76.8% +/- 8.3% for the loaded sites and
      74.1% +/- 10.5% for the unloaded sites. The percentages of new and old bone
      densities were 69.0% +/- 8.3% and 7.8% +/- 3.9% at the loaded sites, and 65.9% +/
      10.3% and 8.2% +/- 4.5% at the unloaded sites, respectively. No statistically
      significant differences were disclosed. CONCLUSION: Applying a delayed load to
      implants supporting single crowns did not yield statistically significant
      differences, and only a tendency of higher osseointegration and bone density was
      observed at loaded sites compared with the unloaded sites.

PMID- 29340353
TI  - Clinical Performance of One-Piece, Screw-Retained Implant Crowns Based on Hand
      Veneered CAD/CAM Zirconia Abutments After a Mean Follow-up Period of 2.3 Years.
AB  - PURPOSE: The aim of this study was to evaluate the clinical performance of one
      piece, screw-retained implant crowns based on hand-veneered computer-aided
      design/computer-aided manufacture (CAD/CAM) zirconium dioxide abutments with a
      crossfit connection at least 1 year after insertion of the crown. MATERIALS AND
      METHODS: Consecutive patients who had received at least one Straumann bone level
      implant and one-piece, screw-retained implant crowns fabricated with CARES
      zirconium dioxide abutments were reexamined. Patient satisfaction, occlusal and
      peri-implant parameters, mechanical and biologic complications, radiologic
      parameters, and esthetics were recorded. RESULTS: A total of 50 implant crowns in
      the anterior and premolar region were examined in 41 patients. The follow-up
      period of the definitive reconstructions ranged from 1.1 to 3.8 years. No
      technical and no biologic complications had occurred. At the reexamination, 100%
      of the implants and reconstructions were in situ. Radiographic evaluation
      revealed a mean distance from the implant shoulder to the first visible bone-to
      implant contact of 0.06 mm at the follow-up examination. CONCLUSION: Screw
      retained crowns based on veneered CAD/CAM zirconium dioxide abutments with a
      crossfit connection seem to be a promising way to replace missing teeth in the
      anterior and premolar region. In the short term, neither failures of components
      nor complications were noted, and the clinical and radiographic data revealed
      stable hard and soft tissue conditions.

PMID- 29340354
TI  - Implant Mandibular Overdentures Retained by Immediately Loaded Implants: A 1-Year
      Randomized Trial Comparing Patient-Based Outcomes Between Mini Dental Implants
      and Standard-Sized Implants.
AB  - PURPOSE: The aim of this 1-year randomized trial was to determine the stability
      and the magnitude of the effect of converting patients' conventional mandibular
      dentures to implant overdentures (IODs) on their satisfaction and oral health
      related quality of life (OHRQoL). The IODs were retained either with two
      immediately loaded interconnected standard-diameter implants or with four
      immediately loaded mini dental implants (MDIs). MATERIALS AND METHODS: Fifty
      completely edentulous subjects complaining about insufficient retention of their
      mandibular dentures were randomly assigned to two groups; 25 patients received
      IODs retained with four MDIs and 25 patients received IODs retained with two
      standard-sized tissue level (STL) interconnected implants. All IODs were opposed
      by conventional maxillary dentures. Patients rated their satisfaction on a 100-mm
      visual analog scale (VAS) and their quality of life on a denture-specific short
      version of the oral health impact profile (OHIP-20) before assignment, and after
      3 and 12 months. A two-way mixed analysis of variance (ANOVA) was conducted to
      assess the change in time and its interaction with treatment mode on patients'
      overall satisfaction ratings, the total OHIP-20, and their specific domain
      scores. RESULTS: Immediate loading was possible for all the patients who received
      the MDIs. By contrast, the immediate loading protocol could be followed for only
      15 of the patients allocated to the STL implant group. For the remaining
      patients, a delayed loading protocol was applied. There was a significant
      improvement in patients' general satisfaction between baseline and 3 months and
      between baseline and 12 months postoperatively (F2,44 = 81.006, P < .001). This
      increase did not differ between the treatment groups (F4,90 = 1.838, P = .128).
      The results also showed a decrease in mean overall OHIP score (F2,43 = 46.863, P
      < .001) between baseline and 3 months and between baseline and 12 months
      postoperatively, indicating a higher level of OHRQoL. In addition, patients
      scored lower 3 and 12 months after treatment than at baseline for all seven
      domains. This decrease did not differ between the treatment groups (F4,88 =
      0.608, P = .658). CONCLUSION: The results suggested that in terms of patient
      based outcomes, mandibular overdentures retained by immediately loaded MDIs can
      offer an improvement of equal magnitude with that achieved by overdentures
      retained by standard-sized implants.

PMID- 29340355
TI  - Human Histologic Evidence of New Bone Formation and Osseointegration Between Root
      Dentin (Unplanned Socket-Shield) and Dental Implant: Case Report.
AB  - The socket-shield technique described 7 years ago has since grown in its
      reporting in the literature as a valid method of ridge preservation at immediate
      implant placement. To date, large clinical cohorts with up-to-4-year follow-up
      have been reported. Additionally, evidence of tissue histology at the dental
      implant and socket-shield has been demonstrated in the animal model. However,
      human histologic evidence has not yet been available, and the clinician's
      uncertainty regarding the tissues that may form between the socket-shield and
      dental implant may remain unanswered until now. This case report presents the
      first human histologic evidence that bone may entirely fill the space between
      root dentin and an osseointegrated implant surface.

PMID- 29340356
TI  - Long-life sodium/carbon fluoride batteries with flexible, binder-free fluorinated
      mesocarbon microbead film electrodes.
AB  - Home-made fluorinated mesocarbon microbeads (F-MCMBs) were synthesised and
      employed in sodium batteries. Flexible, binder-free F-MCMB film electrodes were
      fabricated to enhance the cycle stability, and 65 cycles were achieved, which is
      the longest lifespan reported thus far. Nitrogen-doped graphene nanosheets (N
      GNS) were also introduced as a catalyst, with the aim of lowering the voltage
      gap.

PMID- 29340357
TI  - Expanding the chemical diversity of TNA with tUTP derivatives that are substrates
      for a TNA polymerase.
AB  - Expanding the chemical diversity of threose nucleic acid (TNA) beyond the natural
      bases would enable the development of TNA polymers with enhanced physicochemical
      properties. Here, we describe a versatile approach for increasing the chemical
      diversity of TNA using 5-alkynyl-modified alpha-l-threofuranosyl uridine
      triphosphates that are substrates for a TNA polymerase.

PMID- 29340358
TI  - A strategy for generating aryl radicals from arylborates through organic
      photoredox catalysis: photo-Meerwein type arylation of electron-deficient
      alkenes.
AB  - Photoinduced reactions of arylboronic acids with electron deficient alkenes under
      mild organic photoredox catalysis conditions lead to the formation of Meerwein
      arylation type adducts via the generation of aryl radicals.

PMID- 29340359
TI  - [UCl4(HCN)4] - a hydrogen cyanide complex of uranium tetrachloride.
AB  - The reaction of uranium tetrachloride with anhydrous liquid hydrogen cyanide
      yields a turquoise microcrystalline powder of
      tetrachloridotetraformonitrileuranium(iv), [UCl4(HCN)4]. We determined the
      crystal structure of this compound by powder neutron diffraction. The compound
      was further characterized by IR spectroscopy and thermogravimetric analysis as
      well as by magnetic measurements. The paramagnetic compound crystallizes in the
      tetragonal space group type I4[combining macron]. To the best of our knowledge
      this compound represents the first structurally elucidated uranium(iv) complex
      with HCN as a ligand.

PMID- 29340360
TI  - Saline hybrid nanoparticles with phthalocyanine and tetraphenylporphine anions
      showing efficient singlet-oxygen production and photocatalysis.
AB  - The inorganic-organic hybrid nanoparticles Gd43+[AlPCS4]34- and La43+[TPPS4]34-
      ([AlPCS4]4-: aluminium(iii) chlorido phthalocyanine tetrasulfonate; [TPPS4]4-:
      tetraphenylporphine sulfonate) are shown for the first time. Both were obtained
      via aqueous synthesis and contain extremely high contents of [AlPCS4]34- (81 wt%)
      and [TPPS4]34- (83 wt%). They show efficient singlet oxygen (1O2) production upon
      daylight and red-light irradiation. Photocatalysis is evidenced via dye
      degradation as a proof-of-the-concept and proceeds with daylight and even red
      light illumination.

PMID- 29340362
TI  - Synergetic topography and chemistry cues guiding osteogenic differentiation in
      bone marrow stromal cells through ERK1/2 and p38 MAPK signaling pathway.
AB  - Both the topographic surface and chemical composition modification can enhance
      rapid osteogenic differentiation and bone formation. Till now, the synergetic
      effects of topography and chemistry cues guiding biological responses have been
      rarely reported. Herein, the ordered micro-patterned topography and classically
      essential trace element of strontium (Sr) ion doping were selected to imitate
      topography and chemistry cues, respectively. The ordered micro-patterned
      topography on Sr ion-doped bioceramics was successfully duplicated using the
      nylon sieve as the template. Biological response results revealed that the micro
      patterned topography design or Sr doping could promote cell attachment, ALP
      activity, and osteogenic differentiation of bone marrow-derived mesenchymal stem
      cells (BMSCs). Most importantly, the samples both with micro-patterned topography
      and Sr doping showed the highest promotion effects, and could synergistically
      activate the ERK1/2 and p38 MAPK signaling pathways. The results suggested that
      the grafts with both specific topography and chemistry cues have synergetic
      effects on osteogenic activity of BMSCs and provide an effective approach to
      design functional bone grafts and cell culture substrates.

PMID- 29340361
TI  - A curcumin-loaded polymeric micelle as a carrier of a microRNA-21 antisense
      oligonucleotide for enhanced anti-tumor effects in a glioblastoma animal model.
AB  - A glioblastoma is a common primary brain tumor that expresses microRNA-21 (miR
      21), which inhibits the expression of pro-apoptotic genes such as phosphatase and
      tensin homologue (PTEN) and programmed cell death 4 (PDCD4). Therefore, an
      antisense-oligonucleotide against miR-21 (miR21ASO) could have therapeutic
      effects for glioblastomas. In this study, curcumin was loaded into deoxycholic
      acid-conjugated polyethylenimine (DP) micelles. The curcumin-loaded DP micelle
      (DP-Cur) was evaluated as a carrier for the combined delivery of curcumin and
      miR21ASO. Gel retardation and heparin competition assays showed that DP-Cur
      formed stable complexes with miR21ASO. The anti-tumor effects of the combined
      delivery of curcumin and miR21ASO were evaluated in C6 glioblastoma cells. In
      vitro transfection showed that DP-Cur had an miR21ASO delivery efficiency similar
      to that of polyethylenimine (25 kDa, PEI25k) and DP. In the C6 cells, the
      delivery of miR21ASO using DP-Cur effectively reduced the miR21 level. The
      miR21ASO/DP-Cur complex induced apoptosis more effectively than the single
      delivery of curcumin or miR21ASO. The therapeutic effect of the miR21ASO/DP-Cur
      complex was also evaluated in an intracranial glioblastoma animal model. The
      miR21ASO/DP-Cur complex reduced the tumor volume more effectively than single
      therapy of curcumin or miR21ASO. Immunohistochemistry showed that PDCD4 and PTEN
      were induced in the miR21ASO/DP and miR21ASO/DP-Cur complex groups. Therefore, DP
      Cur is an efficient carrier of miR21ASO and the combined delivery of miR21ASO and
      curcumin may be useful in the development of combination therapy for
      glioblastoma.

PMID- 29340363
TI  - Central-metal effect on intramolecular vibrational energy transfer of M(CO)5Br (M
      = Mn, Re) probed by two-dimensional infrared spectroscopy.
AB  - Vibrational energy transfer in transition metal complexes with flexible
      structures in condensed phases is of central importance to catalytical chemistry
      processes. In this work, two molecules with different metal atoms, M(CO)5Br
      (where M = Mn, Re), were used as model systems, and their axial and radial
      carbonyl stretching modes as infrared probes. The central-metal effect on
      intramolecular vibrational energy redistribution (IVR) in M(CO)5Br was
      investigated in polar and nonpolar solvents. The linear infrared (IR) peak
      splitting between carbonyl vibrations increases as the metal atom changes from Mn
      to Re. The waiting-time dependent two-dimensional infrared diagonal- and off
      diagonal peak amplitudes reveal a faster IVR process in Re(CO)5Br than in
      Mn(CO)5Br. With the aid of density functional theory (DFT) calculations, the
      central-metal effect on IVR time linearly correlates with the vibrational
      coupling strength between the two involved modes. In addition, the polar solvent
      is found to accelerate the IVR process by affecting the anharmonic vibrational
      potentials of a solute vibration mode.

PMID- 29340374
TI  - A well-defined unimolecular channel facilitates chloride transport.
AB  - A unimolecular ion channel was optimized by functionalization with a new type of
      rigid-rod oligomer. The macrocycle pendant endows chloride selectivity and the
      fluorescence feature and suitable length of the rod facilitates the visual
      insertion of channels into the lipid bilayer, resulting in efficient ion
      transport with an EC50 value of 0.36 MUM.

PMID- 29340375
TI  - Enhancement of BMP-2-mediated angiogenesis and osteogenesis by 2-N,6-O-sulfated
      chitosan in bone regeneration.
AB  - Sulfated polysaccharides are attractive semi-synthesized materials that can be
      used as a mimic of heparan sulfate to modulate the protein activity and other
      physiological processes. In this study, we employed sulfated chitosan to enhance
      the angiogenic capacity of bone morphogenic protein-2 (BMP-2). Bone marrow
      stromal cells (BMSCs) cultured in a combination of BMP-2 and 2-N,6-O-sulfated
      chitosan (SCS) group exhibited a higher cell viability and sprouting ability. The
      cells also secreted more VEGF and NO. The expression patterns of angiogenic and
      osteogenic genes were analyzed, and VEGFR2 signaling was found to play a role in
      the enhancing effect of SCS. The chick embryo chorioallantoic membrane (CAM)
      assay revealed an enhanced angiogenic effect of BMP-2 when SCS was involved. In
      addition, we investigated angiogenesis and osteogenesis in mouse using a BMP-2
      induced ectopic bone model. Histological and immune-staining analysis revealed
      that both bone and vascular tissue were enhanced when SCS was added. These data
      prove that SCS can improve the angiogenic potential of BMP-2 and thus lead to
      better bone regeneration.

PMID- 29340376
TI  - The second-harmonic generation intensification derived from localization
      conjugated pi-orbitals in O22.
AB  - Molecular construction with pi-conjugated groups is a favorable strategy to
      discover superior nonlinear optical (NLO) materials. Herein, a novel vanadium
      carbonate compound K3[V(O2)2O]CO3 (KVCO), which combines two different pi-orbital
      groups, delocalized (CO3)2- pi-orbital groups and localized (O2)2- pi-orbital
      groups, was synthesized. Benefiting from the well-arranged [V(O2)2OCO3] unit and
      dual-synergistic pi-d-pi interaction, KVCO has the largest second harmonic
      generation (SHG) effect (about 20 times that of KDP) among the current carbonate
      NLO materials. Moreover, first-principles calculation elucidated the coupling
      enhancement mechanism between (CO3)2-, (O2)2- and VOn groups.

PMID- 29340377
TI  - Metal-organic frameworks at interfaces of hybrid perovskite solar cells for
      enhanced photovoltaic properties.
AB  - In this study, metal-organic frameworks, as an interfacial layer, were introduced
      into perovskite solar cells (PSCs) for the first time. An interface modified with
      the metal-organic framework ZIF-8 efficiently enhanced perovskite crystallinity
      and grain sizes, and the photovoltaic performance of the PSCs was significantly
      improved, resulting in a maximum PCE of 16.99%.

PMID- 29340378
TI  - Chemical dynamics simulations of CID of peptide ions: comparisons between
      TIK(H+)2 and TLK(H+)2 fragmentation dynamics, and with thermal simulations.
AB  - Gas phase unimolecular fragmentation of the two model doubly protonated
      tripeptides threonine-isoleucine-lysine (TIK) and threonine-leucine-lysine (TLK)
      is studied using chemical dynamics simulations. Attention is focused on different
      aspects of collision induced dissociation (CID): fragmentation pathways, energy
      transfer, theoretical mass spectra, fragmentation mechanisms, and the possibility
      of distinguishing isoleucine (I) and leucine (L). Furthermore, discussion is
      given regarding the differences between single collision CID activation, which
      results from a localized impact between the ions and a colliding molecule N2, and
      previous thermal activation simulation results; Z. Homayoon, S. Pratihar, E.
      Dratz, R. Snider, R. Spezia, G. L. Barnes, V. Macaluso, A. Martin-Somer and W. L.
      Hase, J. Phys. Chem. A, 2016, 120, 8211-8227. Upon thermal activation
      unimolecular fragmentation is statistical and in accord with RRKM unimolecular
      rate theory. Simulations show that in collisional activation some non-statistical
      fragmentation occurs, including shattering, which is not present when the ions
      dissociate statistically. Products formed by non-statistical shattering
      mechanisms may be related to characteristic mass spectrometry peaks which
      distinguish the two isomers I and L.

PMID- 29340379
TI  - Enhanced photocatalytic efficiency of C3N4/BiFeO3 heterojunctions: the
      synergistic effects of band alignment and ferroelectricity.
AB  - As one of the most promising photocatalysts, graphitic carbon nitride (g-C3N4)
      shows a visible light response and great chemical stability. However, its
      relatively low photocatalytic efficiency is a major obstacle to actual
      applications. Here an effective and feasible method to dramatically increase the
      visible light photocatalytic efficiency by forming C3N4/BiFeO3 ferroelectric
      heterojunctions is reported, wherein the band alignment and piezo
      /ferroelectricity have synergistic positive effects in accelerating the
      separation of the photogenerated carriers. At the optimum composition of 10 wt%
      BiFeO3, the heterojunction shows 1.4 times improved photocatalytic efficiency
      than that of the pure C3N4. Most importantly, mechanical pressing and electrical
      poling can also improve the photocatalytic efficiencies by 1.3 times and 1.8
      times, respectively. The optimized photocatalytic efficiency is even comparable
      with that of some noble metal based compounds. These results not only prove the
      improved photocatalytic activity of the C3N4-ferroelectric heterojunctions, but
      also provide a new approach for designing high-performance photocatalysts by
      taking advantage of ferroelectricity.

PMID- 29340380
TI  - A DFT study of the adsorption of short peptides on Mg and Mg-based alloy
      surfaces.
AB  - Adsorption of short peptides, including three dipeptides: arginine-glycine (Arg
      Gly), glycine-aspartic acid (Gly-Asp), arginine-aspartic acid (Arg-Asp), and one
      tripeptide arginine-glycine-aspartic acid (RGD), on the surfaces of Mg and Mg
      alloys (Mg-Zn, Mg-Y, and Mg-Nd), was studied using the first-principles
      calculations based on density functional theory (DFT), considering van der Waals
      (vdW) correction. The calculated adsorption energies (Eads) of short peptides on
      the clean Mg(0001) surface are in the range of -1.73 to -2.80 eV per dipeptide,
      and -3.24 eV for RGD. The short peptides prefer to bond to Mg atoms at the
      surface by the O and N anions in their functional groups. For the clean Mg(0001)
      surface, the Eads of the short peptides are exclusively dominated by the number
      of functional groups binding to the surface. However, for the surface of the Mg
      Zn alloy (1% Zn), the adsorption of the peptides is clearly enhanced (by about
      0.3 eV per peptide) due to the enhanced N-Mg bond and the electrostatic
      interactions between the doped Zn at the surface and the backbone chains of the
      peptides. Furthermore, the attractive interactions are increased with the
      increase of doped Zn contents (up to 3%). In contrast, for the surfaces of Mg-Y
      (1% Y) and Mg-Nd (1% Nd) alloys, the adsorption of the peptides is slightly
      weakened compared to that on the clean Mg(0001) surfaces. Our results provide
      useful guidance in understanding the interactions between peptides and the Mg
      based biomedical alloy surfaces at the atomic scale in the biomimetic coating
      fields.

PMID- 29340381
TI  - Unraveling the mystery of "tech red" - a volatile technetium oxide.
AB  - We show that a Tc2O5 molecular species is the likely identity of an unknown
      volatile oxide which has remained uncharacterized for 50+ years. Exploration of
      this molecule's absorption spectra and intermolecular self-interactions provides
      a close match to experimental data and an explanation for volatility and
      resistance to crystallization.

PMID- 29340382
TI  - Tuning the indirect-direct band gap transition in the MoS2-xSex armchair nanotube
      by diameter modulation.
AB  - The application of the reported armchair transition-metal dichalcogenide (MoS2,
      MoTe2, MoSTe and WS2, etc.) nanotube is hindered for the optoelectronic devices
      due to the indirect band gap. By using first-principles calculations, the
      electronic structures of MoS2-xSex single-wall armchair nanotubes with respect to
      different diameters are investigated. The MoS2 armchair nanotube exhibits an
      indirect band gap as a function of nanotube diameters from 10 A to 50 A, whereas
      MoSSe and MoSe2 exhibit a surprising diameter-induced indirect-direct band gap
      crossover at the diameters of 25 A and 33 A, respectively. We also find that the
      optical properties of MoS2-xSex armchair nanotubes are anisotropic and strongly
      depend on the diameter.

PMID- 29340383
TI  - Alamethicin self-assembling in lipid membranes: concentration dependence from
      pulsed EPR of spin labels.
AB  - The antimicrobial action of the peptide antibiotic alamethicin (Alm) is commonly
      related to peptide self-assembling resulting in the formation of voltage
      dependent channels in bacterial membranes, which induces ion permeation. To
      obtain a deeper insight into the mechanism of channel formation, it is useful to
      know the dependence of self-assembling on peptide concentration. With this aim,
      we studied Alm F50/5 spin-labeled analogs in a model 1-palmitoyl-2-oleoyl-sn
      glycero-3-phosphocholine (POPC) membrane, for peptide-to-lipid (P/L) ratios
      varying between 1/1500 and 1/100. Pulsed electron-electron double resonance
      (PELDOR) spectroscopy reveals that even at the lowest concentration investigated,
      the Alm molecules assemble into dimers. Moreover, under these conditions,
      electron spin echo envelope modulation (ESEEM) spectroscopy of D2O-hydrated
      membranes shows an abrupt change from the in-plane to the trans-membrane
      orientation of the peptide. Therefore, we hypothesize that dimer formation and
      peptide reorientation are concurrent processes and represent the initial step of
      peptide self-assembling. By increasing peptide concentration, higher oligomers
      are formed. A simple kinetic model of equilibrium among monomers, dimers, and
      pentamers allows for satisfactorily describing the experimental PELDOR data. The
      inter-label distances in the oligomers obtained from PELDOR experiments become
      better resolved with increasing P/L ratio, thus suggesting that the
      supramolecular organization of the higher-order oligomers becomes more defined.

PMID- 29340384
TI  - Kinetics of the a-C3H5 + O2 reaction, investigated by photoionization using
      synchrotron radiation.
AB  - The kinetics of the combustion-relevant reaction of the allyl radical, a-C3H5,
      with molecular oxygen has been studied in a flow tube reactor at the vacuum
      ultraviolet (VUV) beamline of the Swiss Light Source storage ring, using the CRF
      PEPICO (Combustion Reactions Followed by Photoelectron Photoion Coincidence
      Spectroscopy) setup. The ability to measure threshold photoelectron spectra
      enables a background-free detection of reactive species as well as an isomer
      specific analysis of reaction products. Allyl was generated by direct
      photodissociation of allyl iodide at 266 nm and 213 nm and indirectly by the
      reaction of propene with Cl atoms, which were generated by photolysis from oxalyl
      chloride at 266 nm. Experiments were conducted at room temperature at low
      pressures between 0.8 and 3 mbar using Ar as the buffer gas and with excess O2 to
      maintain nearly pseudo-first-order reaction conditions. Whereas allyl was
      detected by photoionisation using synchrotron radiation, the main reaction
      product allyl peroxy was not observed due to dissociative ionisation of this
      weakly bound species. From the concentration-time profiles of the allyl signal,
      second-order rate constants between 1.35 * 1011 cm3 mol-1 s-1 at 0.8 mbar and
      1.75 * 1011 cm3 mol-1 s-1 at 3 mbar were determined. The rates obtained for the
      different allyl radical generation schemes agree well with each other, but are
      about a factor of 2 higher than the ones reported previously using He as a buffer
      gas. The discrepancy is partly attributed to the higher collision efficiency of
      Ar causing a varying fall-off behavior. When allyl is produced by the reaction of
      propene with Cl atom, an unexpected product is observed at m/z = 68, which was
      identified as 1,3-butadienal in the threshold photoelectron spectrum. It is
      formed in a secondary reaction of allyl with the OCCl radical, which is generated
      in the 266 nm photolysis of oxalyl chloride.

PMID- 29340385
TI  - Coordination supramolecular assemblies of a monohydroxycucurbit[7]uril and their
      potential applications in gas sorption.
AB  - Coordination supramolecular assemblies of monohydroxycucurbit[7]uril ((HO)Q[7])
      with alkaline earth metal ions (AE2+) have been formed in aqueous HCl solution in
      the presence of tetrachloride cadmium anions ([CdCl4]2-) as a structure directing
      agent. The driving force for the assembly could be attributed to the interaction
      of the positive electro-potential outer-surface of (HO)Q[7] molecules with
      [CdCl4]2- anions and ionic dipole interaction of the hydroxyl of (HO)Q[7]
      molecules with [CdCl4]2- anions. Moreover, the porous structure of the
      (HO)Q[7]/AE2+-based coordination supramolecular assemblies could result in
      potential applications in the selective sorption of polar volatile organic
      molecules, which may be useful in molecular sieves, sensors, absorption and
      separation.

PMID- 29340387
TI  - Pb3(SeO3)Br4: a new nonlinear optical material with enhanced SHG response
      designed via an ion-substitution strategy.
AB  - Using an ion-substitution strategy, herein, a new polar material, Pb3(SeO3)Br4,
      with a greatly enhanced SHG response has been successfully designed and
      synthesized through a hydrothermal reaction. Pb3(SeO3)Br4 crystallizes in the NCS
      space group P212121 and consists of a three-dimensional framework formed by
      interconnecting one-dimensional chains, with a good thermal stability up to 230 
      degrees C. This compound exhibits a phase-matchable SHG response as strong as
      that of KH2PO4 (KDP) and a relatively wide mid-infrared (mid-IR) transparent
      window. Moreover, the optical band gap of Pb3(SeO3)Br4 reaches about 3.35 eV,
      thus leading to a high laser damage threshold (LDT) of 67 MW cm-2, which is over
      12 times that of AgGaS2 (<5 MW cm-2) measured under the same condition. All these
      findings suggest that Pb3(SeO3)Br4 would be a candidate for an NLO material in
      the mid-IR region.

PMID- 29340386
TI  - On-chip functional neuroimaging with mechanical stimulation in Caenorhabditis
      elegans larvae for studying development and neural circuits.
AB  - Mechanosensation is fundamentally important for the abilities of an organism to
      experience touch, hear sounds, and maintain balance. Caenorhabditis elegans is a
      powerful system for studying mechanosensation as this worm is well suited for in
      vivo functional imaging of neurons. Many years of research using labor-intensive
      methods have generated a wealth of knowledge about mechanosensation in C.
      elegans, and the recent microfluidic-based platforms continue to push the
      boundary for this field. However, developmental aspects of sensory biology,
      including mechanosensation, are still not fully understood. One current
      bottleneck is the difficulty in assaying larvae because they are much smaller
      than adult worms. Microfluidic devices with features small enough for larvae,
      especially actuators for the delivery of mechanical stimulation, are difficult to
      design and fabricate. Here, we present a series of automatic microfluidic
      platforms that allow for in vivo functional imaging of C. elegans responding to
      controlled mechanical stimulation at different developmental stages. Using a
      novel fabrication method, we designed highly deformable pneumatically actuated on
      chip structures that can deliver mechanical stimulation to larval worms. The PDMS
      actuator allows for quantitatively controlled mechanical stimulation of both
      gentle and harsh touch neurons, by simply changing the actuation pressure, which
      makes this device easily translatable to other labs. We validated the design and
      utility of our systems with studies of the functional role of mechanosensory
      neurons in developing worms; we showed that gentle and harsh touch neurons
      function similarly in early larvae as they do in the adult stage, which would not
      have been possible previously. Finally, we investigated the effect of a sleep
      like state on neuronal responses by imaging C. elegans in the lethargus state.

PMID- 29340388
TI  - Recent progress of particle migration in viscoelastic fluids.
AB  - Recently, research on particle migration in non-Newtonian viscoelastic fluids has
      gained considerable attention. In a viscoelastic fluid, three dimensional (3D)
      particle focusing can be easily realized in simple channels without the need for
      any external force fields or complex microchannel structures compared with that
      in a Newtonian fluid. Due to its promising properties for particle precise
      focusing and manipulation, this field has been developed rapidly, and research on
      the field has been shifted from fundamentals to applications. This review will
      elaborate the recent progress of particle migration in viscoelastic fluids,
      especially on the aspect of applications. The hydrodynamic forces on the
      micro/nano particles in viscoelastic fluids are discussed. Next, we elaborate the
      basic particle migration in viscoelasticity-dominant fluids and elasto-inertial
      fluids in straight channels. After that, a comprehensive review on the
      applications of viscoelasticity-induced particle migration (particle separation,
      cell deformability measurement and alignment, particle solution exchange,
      rheometry-on-a-chip and others) is presented; finally, we thrash out some
      perspectives on the future directions of particle migration in viscoelastic
      fluids.

PMID- 29340389
TI  - The photocatalytic role of electrodeposited copper on pencil graphite.
AB  - We report on the ability of template-electrodeposited copper on pencil graphite
      as a novel and cost effective photocatalyst by considering the photodimerization
      of p-aminothiophenol (p-ATP) to 4,4'-dimercaptoazobenzene.

PMID- 29340390
TI  - Ultrafast stimulated emission of nitrophenolates in organic and aqueous
      solutions.
AB  - Early-time dynamics of nitroaromatics and its coressponding bases can give
      valuable insights into photo-induced reactions relevant to atmospheric and
      environmental processes. In this work, femtosecond broadband absorption
      spectroscopy between 350 and 700 nm has been applied to explore the ultrafast
      dynamics of o-, p- and m-nitrophenol anions (NP-) in basic organic and aqueous
      solution. Excitation at 400 nm promotes these compounds into the first bright
      electronic singlet state, which is a charge-transfer state. A surprising finding
      for all nitrophenolates was a characteristic, spectrally broad stimulated
      emission (SE) from the electronically excited state into the ground state. The
      corresponding lifetime was on the order of a few hundred femtoseconds for o- and
      p-NP- while it was roughly ten times larger for m-NP-. In line with earlier
      observations, the SE is governed by an out-of-plane torsional motion of the nitro
      group, leading to a close energetic approach of the relevant electronically
      excited singlet and ground states. Subsequent dynamics can be assigned to excited
      state absorption and ground state relaxation due to energy dissipation of the
      vibrational modes to the solvent that occur for up to several tens of
      picoseconds. No longer-lasting transient absorption (TA) was found; instead, a
      complete recovery of the ground state bleaching was observed indicating that
      triplet state relaxation is either not significantly involved in this spectral
      part or shifted to other regions. In the aqueous system, time constants for all
      processes are much smaller than in organic solution, a fact that can be explained
      by the larger dipole moment of the solvent and the correspondingly stronger
      intermolecular coupling between NP- and the aqueous solvent.

PMID- 29340391
TI  - Graphene on {116} faceted monocrystalline anatase nanosheet array for ultraviolet
      detection.
AB  - A structure composed of a nanosheet array may trap photons, which could be used
      to enhance the optical response via resonances; this may be highly useful in
      ultraviolet (UV) detection, photocatalysis, solar cells, etc. Moreover, anatase
      nanosheets exposed with the active {001}, {111}, and {116} facets are promising
      in applications such as Li-ion battery, photocatalysis, and electrochemistry.
      Therefore, in this study, the {116} faceted single-crystalline anatase nanosheet
      array with the sheet spacing in the range of several hundred nanometers was
      directly grown on the transparent conductive substrates. A photo-detector was
      fabricated by transferring a graphene electrode to the top of the anatase
      nanosheet array. The resultant device is inactive to visible-light irradiation
      and instantly responds to the UV light, which is due to the unique UV absorption
      property of the anatase nanosheet array and the advantage of the Schottky
      junction between the interfaces of graphene and anatase. The energy barrier
      between the two materials is 0.122 eV. We have provided a thorough research on
      graphene/monocrystal anatase-NSs.

PMID- 29340392
TI  - Enhancing the photoluminescence of surface anchored metal-organic frameworks:
      mixed linkers and efficient acceptors.
AB  - We present two approaches to enhance the photoluminescence quantum yield (PLQY)
      of surface-anchored metal-organic frameworks (SURMOFs). In the first approach we
      fabricate SURMOFs from a mix of an emissive linker with an optically-inert linker
      of equivalent length, diluting the emissive linker while maintaining the SURMOF
      structure. This approach enhances the internal PLQY. However, the increase in
      internal PLQY is achieved at the expense of a drastic reduction in optical
      absorption, thus the external PLQY remains low. To overcome this limitation, a
      second approach is explored wherein energy-accepting guest chromophores are
      infiltrated into the framework of the active linker. At the correct acceptor
      concentration, an internal PLQY of 52% - three times higher than the previous
      approach - is achieved. Additionally, the absorption remains strong leading to an
      external PLQY of 8%, an order of magnitude better than the previous approach.
      Using this strategy, we demonstrate that SURMOFs can achieve PLQYs similar to
      their precursor chromophores in solution. This is of relevance to SURMOFs as
      emitter layers in general, and we examine the optimized emitter layer as part of
      a photon upconversion (UC) SURMOF heterostructure. Surprisingly, the same PLQY is
      not observed after triplet-triplet annihilation in the UC heterostructure as
      after its normal photoexcitation (although the UC layers exhibit low thresholds
      consistent with those reported in our previous work). We discuss the potential
      bottlenecks in energy transport that could lead to this unexpected reduction in
      PLQY after excitation via triplet-triplet annihilation, and how future design of
      SURMOF UC multilayers could overcome these limitations.

PMID- 29340393
TI  - Ferrocenyl-sulfonium ionic liquids - synthesis, characterization and
      electrochemistry.
AB  - New ferrocenylsulfonium cation based ionic liquids were prepared by direct
      alkylation of the corresponding ferrocenyl-based thioethers with N
      alkylbis(trifluoromethanesulfonyl)imides (R'TFSI). This convenient direct access
      to organometallic sulfonium bis(trifluoromethanesulfonyl)imide (TFSI) salts
      without the need for ion exchange was chosen in order to obtain highly pure and
      reversibly redox active room temperature ILs in many cases. In other cases the
      anion cation interaction in the solid state was studied by XRD analyses. Moreover
      a diferrocenylmethylsulfonium tetrafluoroborate with two redox active centers was
      synthesized. The redox chemistry of these sulfonium salts was investigated via
      cyclic voltammetry. Furthermore, UV-Vis spectra and thermoanalytical data are
      discussed. The electron-withdrawing sulfonium group is directly bonded to the
      ferrocenyl unit, therefore this cationic group influences the potential of these
      ionic liquids in a more pronounced way than being anchored to the ferrocenyl unit
      via an organic spacer. With their low absorbance in the visible light and
      reversible, tunable redox potential, these room temperature ILs open perspectives
      as redox mediators in dye sensitized solar cells (DSSCs), as redox electrolytes
      in supercapacitors or as overcharge protection additives in batteries.

PMID- 29340394
TI  - Highly selective hydrosilylation of olefins and acetylenes by platinum(0)
      complexes bearing bulky N-heterocyclic carbene ligands.
AB  - Platinum complexes bearing bulky N-heterocyclic carbene (NHC) ligands, i.e.,
      [Pt(IPr*)(dvtms)] (where, IPr* = 1,3-bis{2,6-bis(diphenylmethyl)-4
      methylphenyl}imidazol-2-ylidene) and [Pt(IPr*OMe)(dvtms)] (where, IPr*OMe = 1,3
      bis{2,6-bis(diphenylmethyl)-4-methoxyphenyl}imidazol-2-ylidene, dvtms =
      divinyltetramethyldisiloxane) catalyse nearly quantitatively and highly or
      completely the selective hydrosilylation of terminal olefins as well as terminal
      or internal acetylenes.

PMID- 29340395
TI  - Boosting electrocatalytic hydrogen evolution by plasmon-driven hot-electron
      excitation.
AB  - High-performance catalysts for electrocatalytic and photoelectrochemical water
      splitting hold great promise for renewable energy conversion and storage. Herein,
      using porous N-doped carbon supported Au nanoparticles as catalysts, we
      demonstrate that the photon-induced localized surface plasmon resonance (LSPR)
      excitation on Au nanoparticles dramatically improves the hydrogen evolution
      reaction (HER), leading to a more than 4-fold increase of current and meanwhile
      affording a markedly decreased overpotential of 99 mV at a current density of 10
      mA cm-2. The HER enhancement can be largely attributed to the efficient charge
      transfer of N-doped carbon that fastens the injection of hot electrons from
      plasmonic Au nanoparticles. This study highlights the increase of HER catalysis
      efficiency by plasmonic excitation and could provide new avenues towards the
      design of higher energy conversion catalytic water splitting systems with the
      assistance of light energy.

PMID- 29340396
TI  - Synthesis and antiproliferative activity of a series of new platinum and
      palladium diphosphane complexes.
AB  - New organometallic complexes [M(dppe)(R)2] {where M = Pt or Pd, dppe = 1,2
      bis(diphenylphosphano)ethane, and R = C6F4H-x (x = 6,5,4), C6F3H2-3,5, C6F3H2
      5,6, C6F3H2-3,6, C6F4(OMe)-4, and C6F4(cyclo-C5H10N)-4, the numbers x refer to
      the positions of the protons in the polyfluoroaryl ligands} were synthesised
      either through transmetalation from the dichlorido complexes [M(dppe)Cl2] or
      through ligand exchange using [M(diene)Cl2] precursor complexes with diene = 1,5
      cyclooctadiene (cod) or 1,5-hexadiene (hex). Alternatively, [M(dppX)Cl(R)]
      complexes with dppX = dppm (1,1-bis(diphenylphosphano)methane), dppe, dppp (1,3
      bis(diphenylphosphano)propane), and dppb (1,4-bis(diphenylphosphano)butane) were
      prepared in decarboxylation reactions from thallium(i) carboxylates Tl(O2CR). The
      different preparative methods were compared in terms of yield and purity.
      Structural and spectroscopic data are reported for the new dppX- and diene-M(R)2
      complexes. Antiproliferative activity was investigated for these new complexes
      against the HT-29 (colon carcinoma) and MCF-7 (breast adenocarcinoma) cell lines,
      and the active compounds of this first series together with organometallic dppX
      or hex PtII or PdII complexes were then included in cell tests using L1210
      (leukaemia cells) and the cisplatin-resistant L1210/DDP cell line. Remarkably,
      promising antiproliferative results were found for a few PtII and PdII complexes,
      while structurally closely related compounds were essentially nontoxic.

PMID- 29340397
TI  - Ligand modification of UiO-66 with an unusual visible light photocatalytic
      behavior for RhB degradation.
AB  - A series of isostructural UiO-66-X (X = H, NH2, Br, (OH)2, (SH)2) catalysts have
      been successfully synthesized by modifying different functional groups on the
      ligand. The effects of the ligand modification of UiO-66 were investigated for
      their photocatalytic activity of Rhodamine B degradation under visible light.
      Surprisingly, UiO-66-NH2 and UiO-66-(OH)2 which have narrow bandgaps and
      excellent visible light absorption do not show outstanding photocatalytic
      performances compared to UiO-66 and UiO-66-Br. Electrochemical test results
      indicated that the conduction band potential of UiO-66-X and the separation
      efficiency of electrons were quite important in these photocatalytic reactions,
      other than the electronic effect as reported. Similar photocatalytic degradation
      behaviors were found for Congo red and methyl orange. Herein, we firstly reported
      different mechanisms of selective degradation in the case of UiO-66, which
      subverted the previous understanding of photodegradation behavior.

PMID- 29340398
TI  - Synthesis and crystal structure of Sr3Bi2O6 and structural change in the
      strontium-bismuth-oxide system.
AB  - The crystal structures and their changing trend in the strontium-bismuth-oxide
      system are critical for the studies of the related systems and their
      applications. The crystal structure of Sr3Bi2O6 was obtained for the first time
      in the space group of R3[combining macron] with a huge unit cell of a = b =
      25.1146(19) A and c = 18.3685(16) A and all bismuth ions are Bi3+ forming [BiO3]
      trigonal pyramids. Sr3Bi2O6 is a key compound for the structural change trend in
      the SrO-Bi2O3 binary oxide system at 1000  degrees C. With a decrease in the
      bismuth content, its valence state changes from +3 to +5 and Bi-O polyhedra
      changes from connected to isolated before Bi(v) appearance. In the system, the
      boundary of the solid solution beta-phase (Sr1-xBixO1+0.5x) at 900  degrees C was
      also determined accurately as 0.770 <= x <= 0.862, experimentally.

PMID- 29340399
TI  - Landscape of gene networks for random parameter perturbation.
AB  - Landscape approaches have been exploited to study the stochastic dynamics of gene
      networks. However, how to calculate the landscape with a wide range of parameter
      variations and how to investigate the influence of the network topology on the
      global properties of gene networks remain to be elucidated. Here, I developed an
      approach for the landscape of random parameter perturbation (LRPP) to address
      this issue. Based on a self-consistent approximation approach, by making
      perturbations to parameters in a given range, I obtained the landscape for gene
      network systems. I applied this approach to two biological models, one for the
      mutual repression model and the other for the embryonic stem (ES) cell
      differentiation network. For the mutual repression model, my results confirm
      quantitatively that positive feedback promotes the robustness of multistability.
      For the ES cell differentiation model, I identify three cell states, representing
      the ES cell, the differentiation cell, and the intermediate state cell,
      respectively. I propose that the intermediate states and the wide range of
      parameter values coming from inhomogeneous cellular environments provide possible
      explanations for the heterogeneity observed in single cell experiments. I also
      offer a counterintuitive result that noise could reduce heterogeneity and promote
      the stability of cell states. These results support that the network topology
      determines the operating principles of the genetic networks, reflected by the
      representative landscapes from LRPP. This work provides a new route to obtain the
      potential landscape for a gene network system given a wide range of parameter
      values and study the influences of the network topology on the global properties
      of the system.

PMID- 29340400
TI  - Femtosecond laser induced underwater superaerophilic and superaerophobic PDMS
      sheets with through microholes for selective passage of air bubbles and further
      collection of underwater gas.
AB  - Controlling underwater bubble behavior on a solid surface is of great research
      significance, particularly in extreme cases. However, the realization of
      artificial underwater superaerophobic or superaerophilic surfaces is still a
      challenge. Herein, a micro/nanoscale hierarchical rough structure was formed on
      polydimethylsiloxane (PDMS) surface by one-step femtosecond laser ablation. The
      as-prepared surface showed superhydrophobicity in air and superaerophilicity in
      water. Interestingly, the wettability of such a PDMS surface could be easily
      switched to in-air superhydrophilicity and underwater superaerophobicity once it
      was further irradiated by oxygen plasma because the surface chemistry changed.
      The original femtosecond laser-structured underwater superaerophilic PDMS surface
      could absorb/capture bubbles, while the plasma-treated underwater superaerophobic
      surface had excellent anti-bubble ability in water. A rough through-microhole
      array PDMS sheet was prepared by a mechanical drilling process and subsequent
      femtosecond laser ablation. The sheet could selectively allow bubbles to pass,
      that is, the porous underwater superaerophilic sheet allowed bubbles to pass
      through, while the porous underwater superaerophobic sheet was able to intercept
      bubbles in a water medium. Using the porous underwater superaerophilic PDMS sheet
      as the core component, a device that has great ability of collecting underwater
      bubbles/gas was also designed.

PMID- 29340401
TI  - A nanopaper-based artificial tongue: a ratiometric fluorescent sensor array on
      bacterial nanocellulose for chemical discrimination applications.
AB  - In the present study, a ratiometric fluorescent sensor array as an artificial
      tongue has been developed on a nanopaper platform for chemical discrimination
      applications. The bacterial cellulose (BC) nanopaper was utilized for the first
      time as a novel, flexible, and transparent substrate in the optical sensor arrays
      for developing high-performance artificial tongues. To fabricate this platform,
      the hydrophobic walls on the BC nanopaper substrates were successfully created
      using a laser printing technology. In addition, we have used the interesting
      photoluminescence (PL) properties of an immobilized ratiometric probe (carbon dot
      Rhodamine B (CD-RhB) nanohybrids) on the nanopaper platform to improve the visual
      discrimination analysis. Heavy metal ions were utilized as model analytes to
      verify the applicability of the fabricated nanopaper-based ratiometric
      fluorescent sensor array (NRFSA). Using the color variation of the NRFSA platform
      upon the addition of heavy metal ions, which have been obtained by a smartphone
      (under an UV irradiation), five heavy metal ions (i.e., Hg(ii), Pb(ii), Cd(ii),
      Fe(iii), and Cu(ii)) have been well-distinguished through the RGB analysis via
      production of the characteristic PL fingerprint-like response patterns for each
      of them. Moreover, the developed optical sensor array was successfully exploited
      to identify the heavy metal ions in the water and fish samples. We have also
      found that the PL spectra, which have been obtained by a spectrofluorometer, of
      the developed NRFSA can be exploited for discrimination applications. We believe
      that the nanopaper-based artificial tongues will provide innovative insights into
      the development of optical sensor arrays towards advanced (bio)chemical
      discrimination applications and can revolutionize the conventional optical sensor
      array technology.

PMID- 29340402
TI  - Palladium-catalysed stereoselective synthesis of 4-(diarylmethylidene)-3,4
      dihydroisoquinolin-1(2H)-ones: expedient access to 4-substituted isoquinolin
      1(2H)-ones and isoquinolines.
AB  - An efficient method has been developed for the stereoselective synthesis of 4
      (diarylmethylidene)-3,4-dihydroisoquinolin-1(2H)-ones 7 through tandem Heck
      Suzuki coupling at rt using easily available substrates. DBU easily converted the
      exocyclic double bond of these compounds to endo, furnishing 8 and 9. Reduction
      of the carbonyl group of 7 was smoothly carried out with borane dimethyl
      sulphide. Subsequent treatment with KOtBu provided an easy access to 4
      substituted isoquinolines 10a if carried out in refluxing 1,4-dioxane, while
      reaction in DMF at rt led to the incorporation of an extra hydroxyl group at the
      benzylic position of the isoquinolines to give 10b. This straightforward and
      metal free procedure would serve as a better alternative to the prevalent
      procedures. Few of the products could also be transformed into heterocyclic
      scaffolds structurally resembling known bioactive compounds.

PMID- 29340403
TI  - Triangular AgAu@Pt core-shell nanoframes with a dendritic Pt shell and enhanced
      electrocatalytic performance toward the methanol oxidation reaction.
AB  - Triangular AgAu@Pt nanoframes with a dendritic Pt shell were synthesized by
      employing Ag nanoprisms as sacrificial templates. Due to the unique frame-like
      nanostructure and ternary components, the AgAu@Pt nanoframes exhibit impressive
      electrocatalytic performance toward the methanol oxidation reaction with much
      higher activity, and better anti-poisoning capability than commercial Pt/C
      catalysts.

PMID- 29340404
TI  - A highly efficient nucleophilic substitution reaction between R2P(O)H and
      triarylmethanols to synthesize phosphorus-substituted triarylmethanes.
AB  - A highly efficient and general nucleophilic substitution reaction between dialkyl
      H-phosphonates or diarylphosphine oxides and triarylmethanols catalyzed by HOTf
      (trifluoromethanesulfonic acid) has been developed. It provides an atom
      economical protocol for the synthesis of various symmetrical and unsymmetrical
      phosphorus-substituted triarylmethanes that constitute an emerging family of
      potent anticancer agents in rich diversity with 40 to 96% yields. The synthetic
      applicability of this protocol is demonstrated by gram-scale preparations.

PMID- 29340405
TI  - Modulating interactions between ligand-coated nanoparticles and phase-separated
      lipid bilayers by varying the ligand density and the surface charge.
AB  - The interactions between nanoparticles and lipid bilayers are critical in
      applications of nanoparticles in nanomedicine, cell imaging, toxicology, and
      elsewhere. Here, we investigate the interactions between nanoparticles coated
      with neutral and/or charged ligands and phase-separated lipid bilayers using
      coarse-grained molecular dynamics simulation. Both penetration and adsorption
      processes as well as the final distribution of the nanoparticles can be readily
      modulated by varying the ligand density and the surface charge of the
      nanoparticles. Completely hydrophobic (neutral) nanoparticles with larger size
      initially preferentially penetrate into the liquid-disordered region of the lipid
      bilayer and finally transfer into the liquid-ordered region; partially
      hydrophilic nanoparticles with low or moderate surface charge tend to either
      distribute in the liquid-disordered region or be adsorbed on the surface of the
      lipid bilayer, while strongly hydrophilic nanoparticles with high surface charge
      always reside on the surface of the lipid bilayer. Interactions of the
      nanoparticles with the lipid bilayers are affected by the surface charge of
      nanoparticles, hydrophobic mismatch, bending of the ligands, and the packing
      state of the lipids. Insight in these factors can be used to improve the
      efficiency of designing nanoparticles for specific applications.

PMID- 29340406
TI  - Clarifying the high on/off ratio mechanism of nanowire UV photodetector by
      characterizing surface barrier height.
AB  - The response of semiconductor nanowire UV sensors represented by ZnO nanowire UV
      sensor is usually explained by the adsorption and desorption of oxygen molecules,
      but with the great increase of these sensors' on/off ratio in recent years, this
      explanation is inadequate and the inner mechanism for the large on/off ratio
      urgently needs to be explored. Here, the distribution of carrier concentration in
      a ZnO nanowire is found to be determined as a function of the radius of the
      nanowire, using a calibrated surface photovoltage method and space charge model.
      A critical radius is indicated which determines the carrier concentration and
      photoresponse behavior of the nanowire. When the radius is below this critical
      value, the carrier concentration in the dark decreases dramatically compared with
      that of the nanowire under UV light illumination. Specifically, a decrease of
      carrier concentration by 4-5 orders of magnitude occurs when the radius is below
      50 nm, which causes the on/off ratio to vary by the same orders of magnitude.
      When the radius is above the critical value, the influence of radius on carrier
      concentration is nonsignificant and the on/off ratio is below 100. Finally, we
      found that the high on/off ratio of the ZnO nanowire should be ascribed to the
      complete depletion of the nanowire led by the interplay of radius and surface
      band bending rather than the change in width of the depletion layer as most
      papers have suggested.

PMID- 29340407
TI  - t-BuONa-mediated direct C-H halogenation of electron-deficient (hetero)arenes.
AB  - An efficient halogenation of electron-deficient (hetero)arenes is described. The
      reaction utilizes common t-BuONa as a catalyst (for iodination) or a promoter
      (for bromination and chlorination), and perfluorobutyl iodide, CBr4 or CCl4 as
      the readily-available halogenating agents, respectively. The protocol features
      broad scope, high efficiency, mild conditions and gram scalability. An ionic
      pathway involving halogen bond formation and halophilic attack is proposed. The
      utility of the resulting iodinated heteroarenes is demonstrated in visible light
      mediated Caryl-Caryl cross-coupling reaction.

PMID- 29340408
TI  - Expanding pore sizes of ZIF-8-derived nitrogen-doped microporous carbon via C60
      embedding: toward improved anode performance for the lithium-ion battery.
AB  - Porous carbon and nanocarbons have been extensively applied as anode materials
      for high-energy density lithium-ion batteries (LIBs). However, as another
      representative nanocarbon, fullerenes, such as C60, have been scarcely utilized
      in LIBs because of their poor electrochemical reversibility. Herein, we designed
      a novel C60-embedded nitrogen-doped microporous carbon material (denoted as C60@N
      MPC), which was derived from a zeolitic imidazolate framework-8 (ZIF-8)
      precursor, demonstrating its promising application as a superior anode material
      for LIB. We first embedded C60in situ into a ZIF-8 matrix via a facile solid
      state mechanochemical route, which acted as a precursor and was transformed to
      C60@N-MPC after carbonization. The C60@N-MPC was applied as a novel anode for
      LIBs, showing an improved reversible specific capacity of ~1351 mA h g-1 at 0.1 A
      g-1 and a better rate capacity (~1077 mA h g-1 at 1 A g-1 after 400 cycles)
      relative to those based on the unmodified N-MPC anode. The role of C60 in the
      superior lithium storage performance of C60@N-MPC was elucidated, revealing that
      C60 functioned as a pore expander for N-MPC with 3-20 nm mesopores (versus sub-1
      nm micropores for the unmodified N-MPC), which facilitated the rapid diffusion of
      the organic electrolyte.

PMID- 29340410
TI  - Active textiles with Janus fibres.
AB  - We describe reshaping of active textiles actuated by bending of Janus fibres
      comprising both active and passive components. A great variety of shapes,
      determined by minimising the overall energy of the fabric, can be produced by
      varying bending directions determined by the orientation of Janus fibres. Under
      certain conditions, alternative equilibrium states, one absolutely stable and the
      other metastable coexist, and their relative energy may flip its sign as system
      parameters, such as the extension upon actuation, change. A snap-through
      reshaping in a specially structured textile reproduces the Venus flytrap effect.

PMID- 29340409
TI  - Dynamics of 3D carcinoma cell invasion into aligned collagen.
AB  - Carcinoma cells frequently expand and invade from a confined lesion, or
      multicellular clusters, into and through the stroma on the path to metastasis,
      often with an efficiency dictated by the architecture and composition of the
      microenvironment. Specifically, in desmoplastic carcinomas such as those of the
      breast, aligned collagen tracks provide contact guidance cues for directed cancer
      cell invasion. Yet, the evolving dynamics of this process of invasion remains
      poorly understood, in part due to difficulties in continuously capturing both
      spatial and temporal heterogeneity and progression to invasion in experimental
      systems. Therefore, to study the local invasion process from cell dense clusters
      into aligned collagen architectures found in solid tumors, we developed a novel
      engineered 3D invasion platform that integrates an aligned collagen matrix with a
      cell dense tumor-like plug. Using multiphoton microscopy and quantitative
      analysis of cell motility, we track the invasion of cancer cells from cell-dense
      bulk clusters into the pre-aligned 3D matrix, and define the temporal evolution
      of the advancing invasion fronts over several days. This enables us to identify
      and probe cell dynamics in key regions of interest: behind, at, and beyond the
      edge of the invading lesion at distinct time points. Analysis of single cell
      migration identifies significant spatial heterogeneity in migration behavior
      between cells in the highly cell-dense region behind the leading edge of the
      invasion front and cells at and beyond the leading edge. Moreover, temporal
      variations in motility and directionality are also observed between cells within
      the cell-dense tumor-like plug and the leading invasive edge as its boundary
      extends into the anisotropic collagen over time. Furthermore, experimental
      results combined with mathematical modeling demonstrate that in addition to
      contact guidance, physical crowding of cells is a key regulating factor
      orchestrating variability in single cell migration during invasion into
      anisotropic ECM. Thus, our novel platform enables us to capture spatio-temporal
      dynamics of cell behavior behind, at, and beyond the invasive front and reveals
      heterogeneous, local interactions that lead to the emergence and maintenance of
      the advancing front.

PMID- 29340411
TI  - Multiplexed detection of nucleic acids using 19F NMR chemical shift changes based
      on DNA photo-cross-linking of 3-vinylcarbazole derivatives.
AB  - The detection methodology for nucleic acids is a useful tool for the analysis of
      biological systems and diagnosis of diseases. We demonstrated the feasibility of
      the detection of any nucleic acids based on large chemical shifts via ultrafast
      DNA photo-cross-linking and the effects of substitution by 3-vinylcarbazole
      derivatives. These chemical shifts enable the sequence-specific detection of any
      strand using hybridization chain reaction.

PMID- 29340413
TI  - Stretch tuning of the Debye ring for 2D photonic crystals on a dielectric
      elastomer membrane.
AB  - The tunable diffracted pattern (Debye ring) of the well-ordered close-packed 2D
      photonic crystal (PC) is achieved via large deformation of the dielectric
      elastomer (DE) membrane for the first time. Two deformation models are proposed,
      the in-plane deformation driven by voltage and the out-of-plane deformation
      actuated by pressure. Both experimental and theoretical analyses are conducted to
      explore the tunability of the DE stretch on the Debye ring of the 2D PC, by
      voltage and pressure. An excellent agreement is found between the experimental
      and analytical results. This study shows that tuning the size of the Debye ring
      by voltage driven in-plane deformation is easy to operate and space-saving.
      However, it needs a high voltage and the adjustable range is relatively small. On
      the other hand, the pneumatic tuning by out-of-plane deformation has a widely
      adjustable range compared with the electric one and the pressure needed is only
      hundreds to less than two thousand pascal, which is energy-saving. This work may
      pave the way for the design of various smart sensors and soft displays with the
      combination of PCs and DEs.

PMID- 29340414
TI  - Nanoparticle separation based on size-dependent aggregation of nanoparticles due
      to the critical Casimir effect.
AB  - Nanoparticles typically have an inherent wide size distribution that may affect
      the performance and reliability of many nanomaterials. Because the synthesis and
      purification of nanoparticles with desirable sizes are crucial to the
      applications of nanoparticles in various fields including medicine, biology,
      health care, and energy, there is a great need to search for more efficient and
      generic methods for size-selective nanoparticle purification/separation. Here we
      propose and conclusively demonstrate the effectiveness of a size-selective
      particle purification/separation method based on the critical Casimir force. The
      critical Casimir force is a generic interaction between colloidal particles near
      the solvent critical point and has been extensively studied in the past several
      decades due to its importance in reversibly controlling the aggregation and
      stability of colloidal particles. Combining multiple experimental techniques, we
      found that the critical Casimir force-induced aggregation depends on relative
      particle sizes in a system with larger ones aggregating first and the smaller
      ones remaining in solution. Based on this observation, a new size-dependent
      nanoparticle purification/separation method is proposed and demonstrated to be
      very efficient in purifying commercial silica nanoparticles in the lutidine/water
      binary solvent. Due to the ubiquity of the critical Casimir force for many
      colloidal particles in binary solvents, this method might be applicable to many
      types of colloidal particles.

PMID- 29340415
TI  - Alkaline-earth metal phenylphosphonates and their intercalation chemistry.
AB  - The intercalation chemistry of layered alkaline-earth metal phenylphosphonates
      with the general formula MeC6H5PO3.2H2O (Ca, Sr, Ba) is reviewed. The preparation
      of the host materials is described and their behavior in dependence on the
      relative humidity and pH of the reaction medium is discussed. Mutual
      relationships between MeC6H5PO3.2H2O and Me(C6H5PO3H)2 were investigated using a
      method of computer-controlled addition of reagents. The MeC6H5PO3.2H2O compounds
      are able to intercalate species having a free electron pair through the so-called
      coordination intercalation. In this way, 1-alkylamines, 1-alkanols, 1,n-diols and
      1,2-diols were intercalated. In the case of the ethanol and methanol intercalates
      of strontium phenylphosphonate we were able to determine the structure of the
      host part by single-crystal X-ray diffraction. By combination of the data
      obtained from the diffraction with molecular modeling we suggested the
      arrangement of the host molecules in the interlayer space of the host. The
      arrangement of the shorter diols in the interlayer space of strontium
      phenylphosphonate was also proposed on the basis of molecular modeling
      calculations. These models help us to understand the structure of the prepared
      intercalates.

PMID- 29340416
TI  - Self-assembly of cationic gemini surfactants, alkanediyl-bis-(dimethyldodecyl
      ammonium bromide), in cyclohexane: effects of spacer length on their association
      into reverse lyotropic liquid crystalline or reverse vesicles.
AB  - Herein, homogeneous solutions of cationic gemini surfactants, alkanediyl
      alpha,omega-bis(dimethyldodecylammonium bromide), referred to as 12-s-12 where s
      = 2, 4, 6, 8, and 10, in cyclohexane have been prepared with the help of sodium
      hexanoate (SH) or sodium laurate (SL). These surfactants self-assembled in
      cyclohexane to form various aggregating structures, which were characterised by
      small-angle X-ray scattering (SAXS) together with polarised microscopy
      observations. The results showed that 12-2-12/SH, where the gemini had the
      shortest spacer among this series, formed an inverse micellar cubic liquid
      crystalline phase of the Fd3m structure. 12-s-12/SL, including s = 4, 6, and 8,
      which contained an adequate length spacer, formed an inverse hexagonal liquid
      crystalline phase packed by the cylindrical assemblies of surfactants. 12-10
      12/SL, in which the gemini had a longer spacer, formed dispersed reverse vesicles
      (a lamellar structure). The rheological properties of liquid crystalline phases
      in a linear visco-elastic regime were studied. 12-2-12/SH formed a hard gel,
      whereas 12-s-12/SL formed soft gels. Dynamic light scattering and steady-state
      viscosity analyses were performed for the reverse vesicle solutions formed by 12
      10-12/SL. In all these systems, the amount of added water W0, denoting the mole
      ratio of water to the gemini surfactant, was demonstrated to influence the
      properties.

PMID- 29340417
TI  - Rose Bengal catalysed photo-induced selenylation of indoles, imidazoles and
      arenes: a metal free approach.
AB  - In this report, the highly efficient Rose Bengal-catalysed C(sp2)-H selenylation
      of indoles, imidazoles and arenes was achieved using a half molar equiv. of
      diorganoyl diselenides. This metal-free, photo-induced protocol resulted in
      selenylated products in good to excellent yields. The reaction features are high
      yields, an atom-economic, gram-scalable and metal-free approach, and
      applicability to different biologically relevant (hetero)arenes.

PMID- 29340423
TI  - Total synthesis of five natural eremophilane-type sesquiterpenoids.
AB  - The first total syntheses of five natural eremophilane-type sesquiterpenoids were
      achieved in 4-12 steps via a common synthetic intermediate. The syntheses feature
      a double Michael addition, Robinson annulation, alpha-enolization of an
      unsaturated ketone, and Pd-catalyzed Suzuki coupling reaction to install the side
      chain. This synthetic strategy could be easily extended to other eremophilane
      type sesquiterpenoids with similar bicyclic skeletons.

PMID- 29340428
TI  - A synergic approach of X-ray powder diffraction and Raman spectroscopy for
      crystal structure determination of 2,3-thienoimide capped oligothiophenes.
AB  - This work presents a Raman based approach for the rapid identification of the
      molecular conformation in a series of new 2,3-thienoimide capped
      quaterthiophenes, whose crystal structures were determined by synchrotron
      radiation X-ray powder diffraction. These systems display two conformational
      polymorphs, known as forms A and B, as a result of the anti-anti-anti and syn
      anti-syn arrangements of the quaterthiophene cores. In a micro-Raman and
      computational study, the spectroscopic differences between the conformers were
      detected and proved to be suitable markers for polymorph identification. Thus,
      the synergic employment of diffraction and Raman spectroscopy techniques yields a
      full and reliable characterization of 2,3-thienoimide capped quaterthiophene
      compounds in their solid state.

PMID- 29340432
TI  - Capture of colloidal particles by a moving microfluidic bubble.
AB  - Foams can be stabilized for long periods by the adsorption of solid particles on
      the liquid-gas interfaces. Although such long-term observations are common,
      mechanistic descriptions of the particle adsorption process are scarce,
      especially in confined flows, in part due to the difficulty of observing the
      particles in the complex gas-liquid dispersion of a foam. Here, we characterise
      the adsorption of micron-scale particles onto the interface of a bubble flowing
      in a colloidal aqueous suspension within a microfluidic channel. Three parameters
      are systematically varied: the particle size, their concentration, and the mean
      velocity of the colloidal suspension. The bubble coverage is found to increase
      linearly with position in the channel for all conditions but with a slope that
      depends on all three parameters. The optimal coverage is found for 1 MUm
      particles at low flow rates and high concentrations. In this regime the particles
      pass the bubbles through the gutters between the interface and the channel
      corners, where the complex 3D flow leads them onto the interface. The largest
      particles cannot enter into the gutters and therefore provide very poor coverage.
      In contrast, particle aggregates can sediment onto the microchannel floor ahead
      of the bubble and get swept up by the advancing interface, thus improving the
      coverage for both large and medium particle sizes. These observations provide new
      insight on the influence of boundaries for particle adsorption at an air-liquid
      interface.

PMID- 29340434
TI  - Structure-induced switching of interpolymer adhesion at a solid-polymer melt
      interface.
AB  - Here we report a link between the interfacial structure and adhesive property of
      homopolymer chains physically adsorbed (i.e., via physisorption) onto solids.
      Polyethylene oxide (PEO) was used as a model and two different chain
      conformations of the adsorbed polymer were created on silicon substrates via the
      well-established Guiselin's approach: "flattened chains" which lie flat on the
      solid and are densely packed, and "loosely adsorbed polymer chains" which form
      bridges jointing up nearby empty sites on the solid surface and cover the
      flattened chains. We investigated the adhesion properties of the two different
      adsorbed chains using a custom-built adhesion testing device. Bilayers of a thick
      PEO overlayer on top of the flattened chains or loosely adsorbed chains were
      subjected to the adhesion test. The results revealed that the flattened chains do
      not show any adhesion even with the chemically identical free polymer on top,
      while the loosely adsorbed chains exhibit adhesion. Neutron reflectivity
      experiments corroborated that the difference in the interfacial adhesion is not
      attributed to the interfacial brodening at the free polymer-adsorbed polymer
      interface. Instead, coarse-grained molecular dynamics simulation results suggest
      that the tail parts of the loosely adsorbed chains act as "connector molecules",
      bridging the free chains and substrate surface and improving the interfacial
      adhesion. These findings not only shed light on the structure-property
      relationship at the interface, but also provide a novel approach for developing
      sticking/anti-sticking technologies through precise control of the interfacial
      polymer nanostructures.

PMID- 29340436
TI  - Dietary pectin and mango pulp effects on small intestinal enzyme activity levels
      and macronutrient digestion in grower pigs.
AB  - The effects of refined pectin and mango pulp on macronutrient digestion and small
      intestinal enzyme activity were studied in grower pigs. Diets based on wheat
      starch with and without apple pectin or dried mango fruit pulp were fed to 30
      grower pigs for 21 days. Pigs were euthanized two hours postprandially, and their
      gastrointestinal contents recovered. Starch and protein digestion as well as
      alpha-amylase activity were all increased in pigs fed pectin. In contrast, fat
      digestion, lipase and protease (trypsin) activities were all significantly
      reduced in these pigs. Pigs fed the mango fruit pulp diet had intermediate
      effects compared with pigs fed refined pectin and control diets. The data
      suggests that pectin has a significant effect on digestive enzyme activity and
      subsequent influence on macronutrient digestion. The fact that pectin caused
      either an increase (alpha-amylase) or decrease (lipase, protease) in enzyme
      activity in digesta, which either did (starch, lipid) or did not (protein)
      associate with residual nutrient differences illustrates the complexity of small
      intestinal responses to added fibre in diets.

PMID- 29340437
TI  - A novel lysosome-targeted fluorogenic probe based on 5-triazole-quinoline for the
      rapid detection of hydrogen sulfide in living cells.
AB  - A fluorogenic probe based on the novel fluorophore 5-triazole-quinoline was
      developed for the detection of hydrogen sulfide, an endogenous signaling molecule
      associated with the development of various diseases. The lysosome-targeted probe
      Lyso-HS was synthesized via C-H direct azidation from 8-aminoquinoline; it was
      able to detect H2S in 1 min and exhibited excellent turn-on ability with 95-fold
      fluorescence enhancement based on a new fluorochrome. The high quenching
      efficiency was further verified using time-dependent density functional theory
      (TDDFT). The probe also exhibited high selectivity and a low detection limit (as
      low as 214.5 nM), which has practical applications for disease detection and
      monitoring.

PMID- 29340438
TI  - [Human rights and democracy in Argentina: challenges for a future agenda].

PMID- 29340439
TI  - [Origin of the scientific arguments underlying qualitative research].
AB  - This article analyzes the origin of the primary arguments that underpin the
      qualitative approach, covering the birthplace of comprehensive and dialectical
      thought in Germany, its expansion into other countries such as France and the
      United States, and its spread into Latin America. The historical journey of the
      text starts with the development of modern science, examining the first empirical
      works in the Chicago School and the subsequent period of ostracism of qualitative
      research. The text also evidences a revival of comprehensive theoretical and
      empirical perspectives from the 1960s onwards, accompanying the cultural movement
      that came to question the great theoretical narratives and give rise to
      reflections on subjectivity. Theoretically, qualitative approaches are now
      considered a promising form of knowledge construction within the social and human
      sciences, with consolidated theories and a process of permanent internal
      critique. Such consolidation is ensured by the researchers' formation of
      conferences and university departments, the existence of books for the training
      of new researchers, and the increased presence of relevant spaces in scientific
      journals.

PMID- 29340440
TI  - [Administration: practices, myths and ideologies].
AB  - Administration in the social field is examined based on an analysis of its
      practices, the rationalist myth and its ideological dimensions. In this way, the
      article discusses the most frequently utilized concepts (administration,
      management, gerencia, gestion) and their etymologies; the limitations of teaching
      administration; the complexity of a practice marked by the dimensions of science,
      art and the social game; and the ideological question underlying the great
      thought factory that the general theory of administration has been since the
      start of the 19th century. The article reflects upon the need to construct a
      theory based in practice contextualized in the global south that goes beyond the
      classic frames of reference and, above all, to transform administration into a
      problem to be discussed outside of the knowledge that recognizes it as a
      technical practice.

PMID- 29340441
TI  - [Theoretical reflections regarding subjects of praxis and subjects of antithesis
      in Brazilian health reform].
AB  - The Brazilian Health Reform has been recognized as a project that transcends the
      sectoral dimension in that it considers an expanded concept of health and social
      determination, which distinguishes it from other health system reforms of the
      twentieth century. This article aims to contribute to the construction of the
      concepts subjects of praxis and subjects of antithesis by discussing certain
      challenges of praxis in the Brazilian Health Reform, the constitution of social
      subjects and the emergence of subjects of antithesis. The article argues that
      theoretical reflection can contribute to political analysis in health and discern
      the power of a praxis that destabilizes the conservative character of the passive
      revolution.

PMID- 29340442
TI  - [Psychological violence against women: What factors increase the risk of this
      kind of intimate partner abuse?]
AB  - Using data from Argentina's National Study on Violence Against Women [Estudio
      nacional sobre violencias contra las mujeres] carried out in 2015, the article
      identifies the risk factors that increase women's vulnerability to psychological
      abuse. Findings show that women who are more prone to be victims of this kind of
      partner violence are those who are less educated, older, do not earn a wage for
      their work, live with children at home, are involved in less "formal" long-term
      relationships, as well as those whose male partners have a lower educational
      level than their own and/or have alcohol problems and/or were victims or
      witnesses of violence during their childhood. The article suggests possible
      intervention strategies to eradicate abuse, which should be primarily targeted at
      empowering women and strengthening their independence from their partners.

PMID- 29340443
TI  - [Gender performativity, medicalization and health in transsexual women in Mexico
      City].
AB  - The World Health Organization and the American Psychological Association consider
      transsexuality a pathology and suggest sex-gender reassignment for the biopsychic
      adjustment of trans people. Through the discursive analysis of experience, this
      study describes the processes of medicalization and gender performativity in
      relation to the health of a group of trans women from Mexico City. For this
      purpose, a qualitative study was conducted in which 10 semi-structured interviews
      were carried out in 2015. As part of medicalization, the pathologization of
      transsexuality generated psychic suffering; on the other hand, sex-gender
      reassignment also entailed additional risks. It is possible to conclude that in
      trans women, violence and exclusion constitute the primary experiences explaining
      their foremost health problems. Therefore, it is suggested that it is necessary
      for discrimination be reduced and for advancements to be made in safer medical
      interventions.

PMID- 29340444
TI  - [Mortality due to hypertensive diseases: evidence from the southern border of
      Mexico in the period 1998-2014].
AB  - This article analyzes patterns of mortality due to hypertensive diseases in the
      southern border of Mexico, as well as the evolution of such mortality in the 1998
      2014 period. The emphasis is directed at the causes "Essential (primary)
      hypertension" (I10X) and "Hypertensive heart disease with heart failure" (I110).
      Using data from the mortality records of the National Health Information System,
      two types of analyses were carried out: cross-sectional analysis and time trends.
      Over the 16 years included in the study, the age-adjusted mortality rates show a
      clear increase. The findings suggest that the higher presence of indigenous
      populations is a trait of importance in the determination of the mortality
      pattern, with the state of Yucatan a case of particular interest. In addition, it
      is the female population that which exhibits the greatest adverse impact.

PMID- 29340445
TI  - [Health universalism in Argentina between 2003 and 2015: assessments and
      challenges based in a macro-institutional approach].
AB  - Debates about universalism in health have been gaining ground in Latin America
      and have entered the policy agenda with differing results. Notwithstanding the
      country's federalism, the most profound changes that took place in Argentina in
      the last decade occurred in the arena of national politics. Based on the
      theoretical contributions of historical neo-institutionalism and implementation
      studies, this paper aims to analyze, from a macro institutional approach, the
      scope of the national policy regarding health universalization. This descriptive
      study is based on secondary sources and the review of research results on the
      implementation of the programs Remediar, Sumar and Plan Nacer in relation to four
      variables: coverage, access, sets of benefits and rights included in the policy.
      Given the characteristics of the Argentine institutional matrix, program
      implementation in subnational scenarios can be expected to confront complex and
      heterogeneous terrain in which the programs acquire new meanings with respect to
      the goal of universality that each poses.

PMID- 29340446
TI  - [Tensions and contradictions in government interventions for the promotion of
      breastfeeding].
AB  - With the purpose of shedding light on the decrease in the practice of
      breastfeeding in rural areas of Mexico, this article looks at the current
      biomedical model and the policies and actions to promote breastfeeding derived
      from the model's theoretical approach. The article also discusses operational
      strategies of the governmental social welfare program Oportunidades. For this
      purpose, the study utilizes the testimonies of 39 young breastfeeding mothers, 11
      mothers and grandmothers and 12 members of the health staff in the Nahuatl
      population of Cuentepec, Morelos, Mexico, which were collected during a previous
      study in 2008 and 2009. It was found that the biomedical model, which permeates
      all actions to promote breastfeeding, reifies people, limits communication,
      devaluates women's traditional knowledge and imposes a discourse that gradually
      discourages the practice of breastfeeding. The article's proposal is to adopt an
      epistemic change in biomedical thought that shifts from a paradigm of simplicity
      to one of complexity, with the purpose of achieving a greater understanding of
      the bio-psycho-socio-cultural processes of human beings.

PMID- 29340447
TI  - [Why don't doctors use early insulinization therapy in patients with diabetes
      mellitus type 2?: A qualitative approach in a Mexican city].
AB  - Early insulinization therapy is regarded as an efficient aid to improve long term
      control and quality of life in patients with diabetes mellitus type 2 (DM2).
      Nevertheless, both patients and medical staff confront barriers in using this
      therapeutic tool. This study employs a qualitative approach to explore the
      barriers to early insulinization among medical staff from the public sector in
      the city of Xalapa, Veracruz, Mexico. Between 2015 and 2016, in-depth interviews
      were conducted with general and specialist physicians offering primary health
      care to patients with DM2. The transcribed interviews were analyzed to extract
      and organize categories and subcategories of barriers among medical staff. These
      barriers were then grouped into three categories and exemplified with interview
      excerpts: barriers coming from the medical staff itself, barriers emerging from
      the doctor-patient interaction, and institutional barriers. Uses for the
      classification obtained are discussed, as are some of the solutions proposed by
      study participants.

PMID- 29340448
TI  - [Uses of madness: towards the recognition of new interpretations of human
      suffering].
AB  - This article addresses the controversy associated with the construct
      schizophrenia/psychosis/madness, indicating the need to acknowledge the
      multiplicity of experiences and interpretations which arise through the use of
      the construct. The plurality and complexity intrinsic to the phenomenon, the
      discrepancies in its possible meanings and the value of first-hand experience are
      indicated as aspects whose recognition is indispensable to both understanding
      suffering and confronting it socio-educationally. Using interviews carried out in
      September 2013 and May 2014 with six people diagnosed at least with
      schizophrenia, who gave their informed consent to participate, these dimensions
      are explored. Additionally, madness is examined from a queer perspective as a
      possible space of political expression that permits new paths and forms of social
      circulation among those afflicted.

PMID- 29340449
TI  - The continuous challenge of Chagas disease treatment: bridging evidence-based
      guidelines, access to healthcare, and human rights.

PMID- 29340450
TI  - Therapeutic drug monitoring of benznidazole and nifurtimox: a systematic review
      and quality assessment of published clinical practice guidelines.
AB  - The pharmacological management of adults with chronic-phase Chagas disease is
      challenging despite it being the recent focus of extensive research. One of the
      challenges in the current clinical practice guidelines (CPGs) landscape is the
      existence of non-evidence-based recommendations for the use of laboratory tests
      in treatment monitoring. This study aimed to systematically assess the quality
      and consistency of recommendations of CPGs on the pharmacological management of
      adults with chronic-phase Chagas disease. Systematic literature searches were
      conducted in MEDLINE, EMBASE, SciELO and Google to identify all published CPGs
      relevant to the pharmacological management of Chagas disease, between January
      2010 and March 2016. Three independent reviewers assessed the quality of each CPG
      using the Appraisal of Guidelines Research and Evaluation (AGREE) II instrument.
      A total of five CPGs were included and the overall quality of the guidelines for
      therapeutic drug monitoring of Chagas disease was moderate-to-low. There was
      considerable variation in the quality of the CPGs across the AGREE II domains.
      The domains of scope/purpose, stakeholder involvement, and clarity of
      presentation were rated well, and the domains of applicability and editorial
      independence received poor ratings. This review showed that the methodological
      quality of CPGs for Chagas disease was generally inappropriate, and there was no
      explicit link between the best available evidence and current recommendations.

PMID- 29340451
TI  - Is waste collection associated with hepatitis B infection? A meta-analysis.
AB  - This meta-analysis, which is based on a previously published systematic review,
      aims to contribute to the scientific discussion on hepatitis B virus (HBV)
      infection in workers who are exposed to domestic and healthcare wastes.
      Publications were sought which had been made available on the data used by
      December 2013 and updated to December 2016. The quality of the included studies
      was assessed according to the guidelines of Loney et al. for the critical
      appraisal of studies on the prevalence or incidence of a health problem. To
      verify the presence of heterogeneity between the papers, we used the Chi-squared
      test based on a Q statistic. A funnel plot was used to test for publication bias.
      All included studies had across-sectional study design. The association between
      exposure to waste and positive serology for the HBV surface antigen (HBsAg)
      showed a significant association [odds ratio (OR) 1.89, 95% confidence interval
      (CI) 1.27-2.86; p = 0.0019]. The prevalence rates of HBsAg and anti-HBc
      seropositivity was 0.04 (95% CI 0.03-0.05) and 0.21 (95% CI 0.14-0.28),
      respectively (p <0.0001). We found no evidence of publication bias. The results
      of this meta-analysis indicate a statistically significant association between
      exposure to solid waste, whether healthcare or domestic, and positive HBV
      infection markers. Therefore, the working conditions of waste collectors should
      be analyzed more closely. Immunization against HBV is recommended as the chief
      preventive measure for all solid waste workers.

PMID- 29340452
TI  - Detection of multidrug-resistant Pseudomonas aeruginosa harboring bla GES-1 and
      bla GES-11 in Recife, Brazil.
AB  - INTRODUCTION: Pseudomonas aeruginosa, an important pathogen globally, presents
      several resistance mechanisms. This study aimed to investigate the presence of
      bla GES in clinical isolates of Pseudomonas aeruginosa obtained from various
      clinical specimens from patients admitted to three different hospitals in Recife,
      Brazil. The Guiana extended spectrum beta-lactamase (GES) enzymes are responsible
      for conferring broad spectrum resistance to beta-lactam drugs, including the
      carbapenems. METHODS: A total of 100 carbapenem-resistant P. aeruginosa isolates
      underwent polymerase chain reaction (PCR) testing to identify bla GES, bla KPC,
      bla SPM-1, bla IMP, and bla VIM. Additionally, PCR products positive for bla GES
      were sequenced. The clonal profiles of these same isolates were then determined
      by means of enterobacterial repetitive intergenic consensus (ERIC)-PCR analysis.
      RESULTS: PCR analysis revealed that four isolates harbored bla GES; DNA
      sequencing showed that two harbored bla GES-1 and two bla GES-11. Beta-lactamase
      genes bla SPM-1, bla IMP, bla VIM, and bla KPC were investigated; none of these
      genes was detected. Automated susceptibility testing methods (Vitek(r)2,
      bioMerieux) showed that the bla GES-1-positive isolates were only susceptible to
      polymyxin B. The patterns obtained with ERIC-PCR methods showed clonal
      relationship between the two isolates that harbored bla GES-11, whereas different
      clonal profiles were found in the isolates harboring bla GES-1. CONCLUSIONS: We
      detected the presence of bacterial isolates positive for two different variants
      of the enzyme GES in three different hospitals from Recife, Brazil. These enzymes
      have a great capacity for dissemination among Gram-negative bacteria and confer
      broad-spectrum resistance to beta-lactam antibiotics and to the carbapenems.

PMID- 29340453
TI  - Seroprevalence and spatial distribution dynamics of Yersinia pestis antibodies in
      dogs and cats from plague foci in the State of Ceara, Northeastern Brazil.
AB  - INTRODUCTION: In Brazil, the plague is established in several foci located mainly
      in the northeastern part of the country, where it alternates between active and
      quiescent periods. These foci in the State of Ceara have high epidemiological
      importance. In addition to other plague detection activities, plague areas can be
      monitored through serological surveys of dogs and cats (domestic carnivores),
      which, following feeding on plague-infected rodents, can develop mild to severe
      forms of the disease and produce long-lasting antibodies. This study aimed to
      characterize the circulation dynamics and spatial distribution of Yersinia pestis
      antibodies in dogs and cats in plague foci areas of Ceara. METHODS: An ecological
      study was conducted to analyze the temporal series and spatial distribution of
      secondary data obtained from domestic carnivore serum surveillance in Ceara's
      plague areas from 1990 to 2014. RESULTS: Joinpoint analysis revealed that the
      overall trend was a reduction in antibody-positive animals. The mean proportion
      of antibody-positivity during the whole study period was 1.5% (3,023/203,311) for
      dogs, and 0.7% (426/61,135) for cats, with more than 4% antibody-positivity in
      dogs in 1997 and 2002. Antibody titers ranging from 1/16 to 1/64 were frequent.
      Despite fluctuations and a significant reduction, in recent years, there were
      antibody-positive animals annually throughout the study period, and the
      localities containing antibody-positive animals increased in number. CONCLUSION:
      Yersinia pestis is actively circulating in the study areas, posing a danger to
      the human population.

PMID- 29340454
TI  - Human leptospirosis in the Federal District, Brazil, 2011-2015: eco
      epidemiological characterization.
AB  - INTRODUCTION: Leptospirosis is an infectious disease that affects more than 5,000
      people per year in Brazil. The Federal District (FD) lacks epidemiological
      studies of human leptospirosis and presents concerning rates of this disease,
      especially considering its lethality. METHODS: Seventy-nine autochthonous human
      cases of leptospirosis between 2011 and 2015 were analyzed, with the probable
      infection location serving as a basis for the collection and analysis of the
      environmental and epidemiological variables. RESULTS: The incidence of the
      disease ranged from 0.68-13.39 per 100,000 inhabitants in 21 of the 31
      administrative regions that compose the FD. The local profile of human
      leptospirosis was predominantly associated with urban areas during the rainy
      season, population access to the sewage network, the treated water network, and
      the public garbage collection service. The vast majority of cases had a strong
      association with synanthropic rodents at the infection sites. CONCLUSIONS: In
      order to prevent and control potentially lethal human leptospirosis infection,
      the eco-epidemiological characterization of this disease is a valuable tool for
      public policies of prevention, control, and surveillance. In addition to
      population awareness, the systematized control of synanthropic rodents could be
      the main health action to reduce the incidence of this disease in the FD.

PMID- 29340455
TI  - Central venous catheter-related infections in patients receiving short-term
      hemodialysis therapy: incidence, associated factors, and microbiological aspects.
AB  - INTRODUCTION: Bloodstream infections are the second most common cause of death
      among patients on hemodialysis. This study aimed to evaluate the incidence of and
      risk factors associated with central venous catheter-related infections in
      patients undergoing hemodialysis, and to identify and characterize the type and
      antimicrobial susceptibility profiles of the primary microorganisms isolated
      during one year of follow-up. METHODS: A prospective cohort study was conducted
      in 2014 in a hemodialysis referral center. We included 200 outpatients with acute
      kidney injury who had no permanent venous access. A nurse assessed the patients
      for signs of infection three times per week during dressing changes. The
      clinicopathologic characteristics of patients with and without local or systemic
      infection were compared. RESULTS: Fifty-five episodes of catheter-related
      infections occurred in 43 (22%) patients; 38 (69%) were bloodstream infections
      and 17 (31%) were local infections. Thirty-two (75%) patients with infection had
      femoral vein catheter placement. In total, 6,240 hemodialysis sessions were
      performed; the rates of primary bloodstream and local infection were 6.1 and 2.7
      episodes per 1,000 patients on daily dialysis, respectively. In the univariate
      analysis, diabetes was significantly associated with the development of
      infection, while level of education, ethnicity, age, and sex were not. Gram
      negative bacteria were primarily isolated from blood culture specimens (55% of
      samples). Of the Gram-negative isolates, 56% were resistant to the carbapenems.
      CONCLUSIONS: We identified a high incidence of catheter-related infections caused
      by resistant microorganisms in patients undergoing hemodialysis via central
      venous catheters.

PMID- 29340456
TI  - New strategy to improve quality control of Montenegro skin test at the production
      level.
AB  - INTRODUCTION: The production of the Montenegro antigen for skin test poses
      difficulties regarding quality control. Here, we propose that certain animal
      models reproducing a similar immune response to humans may be used in the quality
      control of Montenegro antigen production. METHODS: Fifteen Cavia porcellus
      (guinea pigs) were immunized with Leishmania amazonensis or Leishmania
      braziliensis , and, after 30 days, they were skin tested with standard Montenegro
      antigen. To validate C. porcellus as an animal model for skin tests, eighteen
      Mesocricetus auratus (hamsters) were infected with L. amazonensis or L.
      braziliensis , and, after 45 days, they were skin tested with standard Montenegro
      antigen. RESULTS: Cavia porcellus immunized with L. amazonensis or L.
      braziliensis , and hamsters infected with the same species presented induration
      reactions when skin tested with standard Montenegro antigen 48-72h after the
      test. CONCLUSIONS: The comparison between immunization methods and immune
      response from the two animal species validated C. porcellus as a good model for
      Montenegro skin test, and the model showed strong potential as an in vivo model
      in the quality control of the production of Montenegro antigen.

PMID- 29340457
TI  - Diet Quality of patients with chronic Chagas disease in a tertiary hospital: a
      case-control study.
AB  - INTRODUCTION: Nutritional status has been implicated in the modulation of the
      immune response, possibly augmenting the pathogenesis of Chagas disease (Cd). We
      evaluated diet quality and nutritional status in adults and elderly patients with
      chronic Cd in a tertiary hospital. METHODS: A case-control study of Cd patients
      was conducted, paired for gender, age, and co-morbidities with non-Cd patients.
      Anthropometric measurements and food frequency questionnaire was used, and diet
      quality was assessed by the Brazilian Healthy Eating Index-Revised (BHEI-R). The
      Estimated Average Requirement cut-off points were used to determine the dietary
      micronutrient adequacy. The Cd group was further grouped according to Los Andes
      classification. RESULTS: The study participants were 67 +/- 10 years old, 73.6%
      elderly and 63% female. The prevalence of overweight/obesity and abdominal fat
      was high in both groups; however, Cd group showed a lower prevalence of obesity
      and increased risk of disease according to waist circumference classification.
      There was no difference in BHEI-R score between groups (p=0.145). The Cd group
      had sodium and saturated fat intake above recommendations and low intake of
      unsaturated fat, vitamin D, E, selenium, magnesium, and dairy products; but
      higher intake of iron. According to Los Andes classification, group III presented
      lower intake of whole fruit and dietary fiber. CONCLUSIONS: Patients with Cd were
      overweight and the quality of their diet was unsatisfactory based on the
      recommended diet components for age and sex.

PMID- 29340458
TI  - Morbidity of schistosomiasis mansoni in a low endemic setting in Ouro Preto,
      Minas Gerais, Brazil.
AB  - INTRODUCTION: Despite the advances of disease control programs, severe forms of
      schistosomiasis are prevalent. The prevalence of the disease in areas frequented
      by tourists urges for permanent prevention and control. The aim of this study was
      to describe the morbidity of schistosomiasis in the district of Antonio Pereira,
      Ouro Preto, Minas Gerais, Brazil. METHODS: The proportion of positives was
      defined by Kato-Katz coproscopy and urinary POC-CCA rapid test. Hepatosplenic
      form was diagnosed using abdominal ultrasound. RESULTS: Out of 180
      participants,97 were examined by Kato-Katz, with 4 (4.1%) being positive. Thirty
      four (22.1%) out of 154 were positive by POC-CCA. Five (2.8%) of 177 examined by
      ultrasound had hepatosplenic form. One of them had undergone splenectomy. One
      (0.6%)participant had myeloradiculopathy. CONCLUSIONS: Severe forms of
      schistosomiasis are still prevalent in low endemic areas and should be thoroughly
      investigated.

PMID- 29340459
TI  - Ectopic forms of schistosomiasis mansoni in the second macroregion of Alagoas:
      case series report and review of the literature.
AB  - INTRODUCTION: Ectopic forms of schistosomiasis are those in which the parasitic
      element is localized outside the portal system, the natural habitat of the
      helminth. Although the prevalence rates of schistosomiasis are high in Brazil,
      clinical and epidemiological data on ectopic forms of the disease are still
      scarce. METHODS: Cross-sectional, retrospective and descriptive epidemiological
      study in which cases with a confirmed histopathological diagnosis of an ectopic
      form of schistosomiasis were analyzed. The cases were selected from a database of
      the anatomic pathology files of a referral center. RESULTS: Of the 21 cases
      identified, seven affected the female genital tract and five the male genital
      tract; four cases were identified in the peritoneum; two cases involved lymph
      nodes and two involved adipose tissue; and renal involvement was detected in one
      case. CONCLUSIONS: The lack of knowledge of the clinical presentation of ectopic
      forms of schistosomiasis makes the early identification and treatment of this
      form difficult, with direct implications in the reduction of morbidity and
      mortality in endemic areas.

PMID- 29340460
TI  - First serologic evidence of human hantavirus infection in Alagoas State in
      Northeastern Brazil.
AB  - INTRODUCTION: Hantavirus cardiopulmonary syndrome (HCPS) is rare in Northeastern
      Brazil. METHODS: Prospective surveillance was conducted over a two-year period in
      Alagoas State, Northeastern Brazil. The prevalence of anti-hantavirus N-antigen
      IgM and IgG in human serum samples was determined by enzyme-linked immunosorbent
      assay testing. RESULTS: High avidity IgG was found in nine of 476 serum samples
      tested (from 102 patients with clinical manifestations compatible with HCPS, 124
      patients with leptospirosis, and 250 healthy rural workers). CONCLUSIONS:
      Serologic evidence of past hantavirus infection in residents of Alagoas State
      indicates that hantaviruses are present in northeastern Brazil, even in areas
      silent for HCPS.

PMID- 29340461
TI  - Synanthropic triatomines as potential vectors of Trypanosoma cruzi in Central
      Brazil.
AB  - INTRODUCTION: Chagas disease surveillance requires current knowledge on
      synanthropic triatomines. We analyzed the occurrence and Trypanosoma cruzi
      infection rates of triatomine bugs in central Brazil, during 2012-2014. METHODS:
      Triatomines were collected inside or around houses, and T. cruzi infection was
      determined by optical microscopy and conventional/quantitative polymerase chain
      reaction. RESULTS: Of the 2706 triatomines collected, Triatoma sordida was the
      most frequent species in Goias State, whereas Panstrongylus megistus predominated
      in the Federal District. Parasites identified were T. cruzi, T. rangeli, and
      Blastocrithidia sp. CONCLUSIONS: P. megistus and T. sordida sustained the risk of
      T. cruzi transmission to humans in central Brazil.

PMID- 29340462
TI  - Rhodnius stali: new vector infected by Trypanosoma rangeli (Kinetoplastida,
      Trypanosomatidae).
AB  - INTRODUCTION: Rhodnius stali infection by Trypanosoma rangeli is reported in this
      study for the first time. METHODS: The triatomines were collected from the campus
      of the Federal University of Acre in Rio Branco, Acre, Brazil. The identification
      of T. rangeli was confirmed by multiplex polymerase chain reaction. RESULTS: The
      examinations of two specimens revealed R. stali infection by the epimastigote
      forms of T. rangeli. CONCLUSIONS: The encounter of R. stali infected by T.
      rangeli generates an alert for the state of Acre, since the simultaneous presence
      with Trypanosoma cruzi can make the differential diagnosis of Chagas disease
      difficult.

PMID- 29340463
TI  - Prevalence of and risk factors associated with the presence of Staphylococcus
      aureus in the chronic wounds of patients treated in primary health care settings
      in Brazil.
AB  - INTRODUCTION: Wounds can be colonized by methicillin-resistant Staphylococcus
      aureus (MRSA). METHODS: We evaluated the prevalence of S. aureus and MRSA in the
      wounds of patients treated at Basic Health Units in Brazil and identified risk
      factors associated with their presence. RESULTS: The prevalence rates of S.
      aureus and MRSA were 51.5% and 8.7%, respectively. There was a correlation
      between the presence of S. aureus in wounds and nostrils (p<0.01). A positive
      association was detected between S. aureus infection and previous
      benzylpenicillin use (p=0.02). No associations were observed for MRSA.
      CONCLUSIONS: Multidrug-resistant pathogens are present in primary healthcare
      settings in Brazil.

PMID- 29340464
TI  - Seroprevalence of human Trypanosoma cruzi infection in the North of Estado de
      Mexico.
AB  - INTRODUCTION: Chagas disease is a neglected public health problem in Mexico;
      however, detailed studies to determine the seroprevalence in some states have not
      been performed. METHODS: A total 1,504 human serum from thirteen communities in
      Estado de Mexico, were analyzed with three diagnostics techniques. RESULTS: The
      overall seroprevalence was 9.1%, with high prevalence among people aged 51-60
      years, while people aged 0-29 years were seronegative against T. cruzi.
      CONCLUSIONS: Our data demonstrated the seroprevalence of T. cruzi in the North of
      the Estado de Mexico, an area considered as non-endemic; however, epidemiological
      conditions necessary for natural transmission were found.

PMID- 29340465
TI  - Variability in the clinical distributions of Candida species and the emergence of
      azole-resistant non-Candida albicans species in public hospitals in the Midwest
      region of Brazil.
AB  - INTRODUCTION: Incidence and antifungal susceptibility of Candida spp. from two
      teaching public hospitals are described. METHODS: The minimum inhibitory
      concentrations of fluconazole, voriconazole, itraconazole, and amphotericin B
      were determined using Clinical Laboratory Standard Institute broth microdilution
      and genomic differentiation using PCR. RESULTS: Of 221 Candida isolates, 50.2%
      were obtained from intensive care unit patients; 71.5% were recovered from urine
      and 9.1% from bloodstream samples. Candida parapsilosis sensu stricto was the
      most common candidemia agent. CONCLUSIONS: We observed variations in Candida
      species distribution in hospitals in the same geographic region and documented
      the emergence of non-C. albicans species resistant to azoles.

PMID- 29340466
TI  - Schistosomiasis in the Amazon region: is the current diagnostic strategy still
      appropriate?
AB  - INTRODUCTION: This study analyzed the performance of the Kato Katz technique in
      detecting intestinal schistosomiasis in the State of Para. METHODS: Of three
      stool samples provided by each of 380 participants, a total of 16 Kato Katz
      slides were examined to define the reference value (RV) of positives for
      comparisons. RESULTS: The RV revealed 37 (9.7%) infected participants in contrast
      to 10 (2.6%) according to a single slide. CONCLUSIONS: This significant
      underestimation of the infection rate gives reason to discuss if the current
      classification of prevalence levels reflects the real situation, principally in
      low transmission areas, like the Amazon region.

PMID- 29340467
TI  - Prevalence of and risk factors for intestinal parasite infections in pediatric
      patients admitted to public hospitals in Southern Brazil.
AB  - INTRODUCTION: This study aimed to evaluate the prevalence of intestinal
      parasitosis and to identify risk factors associated therewith in hospitalized
      children. METHODS: Three fecal samples from each patient were evaluated using
      three different techniques. The patients' nutritional and socioeconomic status
      and hematologic profiles were evaluated. RESULTS: Of 106 children, 32.1% tested
      positive for intestinal parasitosis. The associated risk factors were low
      parental education levels and children's nail-biting habit. Eosinophilia,
      observed in 15 cases, was not associated with parasitosis. CONCLUSIONS: We
      recommend routine fecal parasitologic examination for hospitalized children and
      implementation of educational campaigns on the prevention of these diseases.

PMID- 29340468
TI  - Serosurvey of Leptospira spp. and Toxoplasma gondii in rats captured from two
      zoos in Southern Brazil.
AB  - INTRODUCTION: Norway rats (Rattus norvegicus) are zoonotic reservoirs for
      Leptospira spp. and Toxoplasma gondii, and influence diseases in urban areas.
      METHODS: Free-ranging and laboratory-raised rats from two zoos in southern Brazil
      were tested for Leptospira spp. and T. gondii using microscopic agglutination and
      modified agglutination tests, respectively. RESULTS: Overall, 25.6% and 4.6% free
      ranging rats tested positive for Leptospira spp. and T. gondii, respectively,
      with co-seropositivity occurring in two animals. For laboratory-raised rats, 20%
      tested positive for Leptospira spp. Also, Leptospira biflexa serovar Patoc and
      Leptospira noguchii serovar Panama were found. CONCLUSIONS: Serosurveys can show
      the environmental prevalence of zoonotic pathogens.

PMID- 29340469
TI  - Sofosbuvir and daclatasvir combination therapy for current hepatitis C virus
      genotype 4 achieves SVR: a case report of HCV genotype 4 from the Amazon.
AB  - Hepatitis C is a worldwide endemic disease. However, hepatitis C virus genotype 4
      (HCV GT-4) has rarely been reported in Brazil. HCV GT-4 demonstrates high
      sustained virological response (SVR). Here, we report the case of a 62-year-old
      HCV GT-4 positive woman complaining of a headache, nausea, and arthralgia. The
      patient was treated according to the protocol for genotype 4 (12 weeks
      administration of 400mg sofosbuvir and 60mg daclatasvir daily) and achieved SVR.
      Although this is not an Amazonas autochthonous case, the presence of genotype 4
      is rarely reported in the region.

PMID- 29340470
TI  - Traumatic rupture of liver hydatid cysts into the peritoneal cavity of an 11-year
      old boy: a case report from Iran.
AB  - This is the first published case report of an 11-year-old patient with a rupture
      of a liver hydatid cyst (HC) into the peritoneal cavity after an abdominal trauma
      in Iran. The disease was diagnosed using focused abdominal sonography for trauma.
      To date, no cases of traumatic ruptures of liver HCs in children have been
      reported in Iran. In the endemic regions of the world, where patients suffer from
      a history of trauma and constant abdominal symptoms or anaphylactic shock, early
      diagnosis of HC is crucial as it may disseminate to other organs. The condition
      needs conservative surgery and follow-up.

PMID- 29340471
TI  - Epididymo-orchitis caused by Histoplasma capsulatumin a Colombian patient.
AB  - Although histoplasmosis is generally a self-limited disease, disseminated
      infection can occur in patients lacking effective cell-mediated immunity,
      reaching virtually every organ, even the genitourinary tract in rare cases. We
      report a case of epididymo-orchitis in an immunocompetent 38-year-old bricklayer
      from the rural area of Villeta, Cundinamarca, Colombia. The patient presented
      with testicular pain and macroscopic scrotal changes requiring a left
      orchiectomy, with microbiological isolation and molecular confirmation of
      Histoplasma capsulatum.

PMID- 29340472
TI  - Disseminated cutaneous sporotrichosis in patient with alcoholism.
AB  - Sporotrichosis is the most prevalent subcutaneous mycosis and is characterized by
      a subacute or chronic development of a cutaneous or subcutaneous nodular lesion.
      It is caused by the dimorphic fungus Sporothrix spp, which may manifest in
      different clinical forms. The disseminated cutaneous form is uncommon and is more
      likely to occur in immunocompromised patients. We report a 47-year-old male
      patient with multiple cutaneous and subcutaneous nodules. The patient was
      diagnosed with disseminated cutaneous sporotrichosis based on the isolation and
      identification of Sporothrix spp. The patient was treated with potassium iodide,
      which resulted in clinical improvement of the lesions.

PMID- 29340473
TI  - A case of brucellar spondylitis with lumbar spondylolisthesis.

PMID- 29340474
TI  - Cryptococcosis in a transplanted kidney allograft.

PMID- 29340476
TI  - Erratum.
AB  - [This corrects the article doi: 10.1590/0037-8682-0258-2017].

PMID- 29340475
TI  - A proposal for the use of standardized abbreviations for the genera of triatomine
      bugs (Reduviidae: Triatominae) across the World.

PMID- 29340477
TI  - Occurrence of gastrointestinal parasites in wild animals in State of Parana,
      Brazil.
AB  - The objective of this study was to determine the prevalence and diversity of
      gastrointestinal parasites in fecal samples from wild birds and mammals from the
      State of Parana. In total, 220 stool samples were sent to Parasitic Diseases
      Laboratory of the Federal University of Parana during 13 months (Jan/2013
      Jan/2014). A total of 52.7% (116/220) of the animals were positive for cysts,
      oocysts, eggs and/or trophozoites. In birds, the positivity rate was 37.9%
      (25/66) and mammals was 59.1% (91/154). Strongyloidea superfamily eggs were
      observed in 37.3% (82/220) of the samples, Eimeria spp. in 10% (22/220), and
      Trichuris spp. in 4.5% (10/220). The most frequent mammal species were llamas
      (Lama glama), and dromedaries (Camelus bactrianus) with infection rate of 70.1%
      (54/77) and 60.8% (14/23), respectively. In other hand, cockatiels (Nymphicus
      hollandicus) and ring necks (Psittacula krameri), were the most researched birds,
      with infection rate of 20% (40/50) and 100% (6/6), respectively. A high
      prevalence of gastrointestinal parasites was observed in most of wildlife
      animals. Further investigations should be conducted focusing on parasite control
      strategies and the conservation measurements for harmonizing the human-animal
      interaction on the long-term, reducing associated health risks.

PMID- 29340478
TI  - The long and successful journey of electrochemically active amino acids. From
      fundamental adsorption studies to potential surface engineering tools.
AB  - Proteins have been the subject of electrochemical studies. It is possible to
      apply electrochemical techniques to obtain information about their structure due
      to the presence of five electroactive amino acids that can be oriented to the
      outside of the peptidic chain. These amino acids are L-Tryptophan (L-Trp), L
      Tyrosine (L-Tyr), L-Histidine (L-His), L-Methionine (L-Met) and L-Cysteine (L
      Cys); their electrochemical behavior being subject of extensive research, but it
      is still controversial. No spectroscopic investigations have been reported on L
      Trp, and due to the short life time of the intermediates, ex situ techniques
      cannot be employed, leading to a never-ending discussion about possible
      intermediates. In the L-Tyr and L-His cases, spectroelectrochemical studies were
      performed and different intermediates were observed, suggesting that some
      intermediates may be observed under specific conditions, as proposed for L-Cys.
      This amino acid is the most interesting among the electroactive ones because of
      the presence of a thiol moiety at its side chain, leading to a wide range of
      oxidation states. It can adsorb onto surfaces of different crystallographic
      orientation in stereoselective conformation, modifying the surface for different
      applications.as a surface engineering tool since it plays the role of as an
      anchor for the growing of nanocrystals inside proteic templates.

PMID- 29340479
TI  - Enzymes immobilized in Langmuir-Blodgett films: Why determining the surface
      properties in Langmuir monolayer is important?
AB  - In this review we discuss about the immobilization of enzymes in Langmuir
      Blodgett films in order to determine the catalytic properties of these
      biomacromolecules when adsorbed on solid supports. Usually, the conformation of
      enzymes depends on the environmental conditions imposed to them, including the
      chemical composition of the matrix, and the morphology and thickness of the film.
      In this review, we show an outline of manuscripts that report the immobilization
      of enzymes as LB films since the 1980's, and also some examples of how the
      surface properties of the floating monolayer prepared previously to the transfer
      to the solid support are important to determine the efficiency of the resulting
      device.

PMID- 29340480
TI  - Bone repair access of BoneCeramicTM in 5-mm defects: study on rat calvaria.
AB  - OBJECTIVE: The aim of this study was to evaluate the osteoconductive potential of
      BoneCeramicTM on bone healing in rat calvaria 5-mm defects. MATERIAL AND METHODS:
      A 5-mm calvaria bone defect was induced in three groups and the defect was not
      filled with biomaterial [Clot Group (CG)], autogenous bone (AG), or Bone Ceramic
      Group (BCG). Animals were euthanized after 14 or 28 days and the bone tissue
      within the central area of the bone defect was evaluated. Results were compared
      using ANOVA and Tukey test (p<0.05). Immunohistochemistry was performed using
      primary antibodies against osteocalcin, RUNX-2, TRAP, VEGF proteins, and 3
      dimensional images of the defects in MUCT were obtained to calculate bone mineral
      density (BMD). RESULTS: In BCG, the defect was completely filled with biomaterial
      and new bone formation, which was statistically superior to that in the GC group,
      at both time-points (p<0.001 for 14 days; p=0.002 for 28 days). TRAP protein
      showed weak, RUNX-2 showed a greater immunolabeling when compared with other
      groups, VEGF showed moderate immunostaining, while osteocalcin was present at all
      time-points analyzed. The MUCT images showed filling defect by BCG (BMD= 1337 HU
      at 28 days). CONCLUSION: Therefore, the biomaterial tested was found to be
      favorable to fill bone defects for the reporting period analyzed.

PMID- 29340481
TI  - Evaluation of the sealing ability of different root canal sealers: a combined SEM
      and micro-CT study.
AB  - OBJECTIVE: The purpose of this study was to analyze the ability of multiple
      compounds to seal the dental tubules using scanning electron microscopy (SEM) and
      micro-computed tomogra-phy (micro-CT). MATERIAL AND METHODS: Twenty-four single
      root human mandibular premolars were selected and instrumented with nickel
      titanium rotary file and the final file size was #40/06. They were then randomly
      allocated into 2 groups, and all samples were filled with single cone gutta
      percha (#40/06) and one of the tested sealers (AH Plus and EndoSequence BC
      sealers). All specimens were scanned using micro-CT and then three from each
      group were randomly selected for SEM analysis. RESULTS: According to SEM, both
      root canal sealers showed sufficient adaptation to dentin along the whole length
      of the root canal, though the coronal sections presented superior sealing than
      the apical sections. Micro porosity analyses revealed that the volume of closed
      pores and the surface of closed pores had the largest values in the coronal
      sections, followed by the middle and the apical sections for both sealants
      (p<0.05). However, no significant difference was observed for those two
      parameters between AH Plus and EndoSequence BC sealers in any of the three
      sections (p>0.05), whereas they were larger in the apical section when the AH
      Plus sealer was used. CONCLUSIONS: By using the single cone technique, neither
      EndoSequence or AH Plus pro-vides a porosity-free root canal filling. The
      EndoSequence BC sealer may have similar sealing abilities regarding the whole
      root canal as the AH Plus sealer. A better sealing effect could be obtained in
      the coronal and middle sections of a root canal than the apical part by using the
      tested sealers.

PMID- 29340482
TI  - Clear cell odontogenic carcinoma of the mandible: a treatment strategy.
AB  - Clear cell odontogenic carcinoma (CCOC) is a rare odontogenic tumor of the jaws,
      histologically characterized by the presence of agglomerates of cells with
      eosinophilic cytoplasm. The patient, a 62-year-old Caucasian woman, presented an
      intraosseous lesion in the mandibular symphysis. A clinical examination revealed
      a discrete volumetric increase with a hard consistency, palpable to extraoral and
      intraoral examinations. Imaging studies revealed an extensive radiolucent area,
      without defined limits, extending from the region of the right second premolar to
      the left canine. Incisional biopsy analysis indicated a diagnosis of CCOC. The
      treatment proposed was segmental resection of the mandible with a safety margin.
      After six months without recurrence, definitive mandibular reconstruction was
      performed using an iliac crest graft, followed by rehabilitation with implant
      supported denture after five months. After three years of post-resection follow
      up, the patient has shown no evidence of recurrence or metastasis. She continues
      to be under follow-up. To conclude, CCOC must be considered a malignant tumor
      with aggressive behavior. Previous studies have shown that resection with free
      margins is a treatment with a lower rate of recurrence. Nevertheless, long-term
      follow-up is necessary for such patients.

PMID- 29340483
TI  - Idiopathic pulmonary fibrosis in Brazil: challenges for epidemiological
      characterization and management.

PMID- 29340484
TI  - Evolution in the management of non-small cell lung cancer in Brazil.

PMID- 29340486
TI  - Tree-in-bud pattern.

PMID- 29340485
TI  - Noninvasive positive airway pressure: from critically ill patients to physical
      exercise in outpatients.

PMID- 29340487
TI  - Understanding diagnostic tests. Part 2.

PMID- 29340488
TI  - Impact of continuous positive airway pressure on the pulmonary changes promoted
      by immersion in water.
AB  - OBJECTIVE: To determine whether different levels of CPAP improve the lung volumes
      and capacities of healthy subjects immersed in water. METHODS: This was a
      randomized clinical trial, conducted between April and June of 2016, involving
      healthy female volunteers who were using oral contraceptives. Three 20-min
      immersion protocols were applied: control (no CPAP); CPAP5 (CPAP at 5 cmH2O); and
      CPAP10 (CPAP at 10 cmH2O). We evaluated HR, SpO2, FVC, FEV1, the FEV1/FVC ratio,
      peak expiratory flow rate (PEFR), and FEF25-75%) at three time points: pre
      immersion; 10 min after immersion; and 10 min after the end of each protocol.
      RESULTS: We evaluated 13 healthy volunteers. The CPAP10 protocol reversed the
      restrictive pattern of lung function induced by immersion in water, maintaining
      pulmonary volumes and capacities for a longer period than did the CPAP5 protocol.
      CONCLUSIONS: When the hemodynamic change causing a persistent lung disorder, only
      the application of higher positive pressures is effective in maintaining long
      term improvements in the pulmonary profile.

PMID- 29340489
TI  - Tuberculosis infection among primary health care workers.
AB  - OBJECTIVE: To estimate the prevalence of and determine the risk factors
      associated with latent Mycobacterium tuberculosis infection (LTBI) among primary
      health care workers in the city of Vitoria, Brazil. METHODS: This was a cross
      sectional study with data collected through a survey regarding socio-demographic,
      occupational, clinical, and exposure characteristics, as well as knowledge about
      tuberculosis, conducted between 2011 and 2012. All participants underwent a
      tuberculin skin test (TST), and TSTs were read at 72 h by a trained professional.
      RESULTS: A total of 218 primary health care workers participated in the study.
      The prevalence of TST positivity at the >= 10-mm and >= 5-mm cut-off points was,
      respectively, 39.4% (95% CI: 32.9-45.9) and 54.1% (95% CI: 47.4-60.7). Regarding
      occupational categories, community health agents had the highest proportion of
      TST positivity, regardless of the cut-off point (>= 10 mm: 47.5%; and >= 5 mm:
      60.5%). Regarding factors associated with TST results, "having had a previous
      TST" showed a statistically significant association with TST positivity at the >=
      10-mm and >= 5-mm cut-off points (OR = 2.5 [95% CI: 1.17-5.30] and OR = 2.18 [95%
      CI: 1.23-3.87], respectively). CONCLUSIONS: The prevalence of LTBI was found to
      be high among the primary health care workers in this sample. Therefore, we
      recommend the establishment of a periodic screening program for LTBI and
      implementation of effective biosafety policies for the prevention of this
      infection among primary health care workers.

PMID- 29340490
TI  - Accuracy of closed pleural biopsy in the diagnosis of malignant pleural effusion.
AB  - OBJECTIVE: Previous studies have demonstrated that closed pleural biopsy (CPB)
      has a sensitivity of less than 60% for diagnosing malignancy. Therefore,
      controversy has recently emerged regarding the value of CPB as a diagnostic test.
      Our objective was to assess the accuracy of CPB in diagnosing malignancy in
      patients with pleural effusion. METHODS: This was a prospective 8-year study of
      individuals who underwent CPB to establish the etiology of pleural effusion.
      Information on each patient was obtained from anatomopathological reports and
      medical records. When CPB findings showed malignancy or tuberculosis, the biopsy
      was considered diagnostic, and that was the definitive diagnosis. In cases in
      which biopsy histopathological findings were nonspecific, a definitive diagnosis
      was established on the basis of other diagnostic procedures, such as
      thoracoscopy, thoracotomy, fiberoptic bronchoscopy, biochemical and cellular
      measurements in pleural fluid, and/or microbiological tests. The accuracy of CPB
      was determined with 2 * 2 contingency tables. RESULTS: A total of 1034 biopsies
      from patients with pleural effusion were studied. Of those, 171 (16.54%) were
      excluded from the accuracy analysis either because of inadequate samples or
      insufficient information. The results of the accuracy analysis were as follows:
      sensitivity, 77%; specificity, 98%; positive predictive value, 99%; negative
      predictive value, 66%; positive likelihood ratio, 38.5; negative likelihood
      ratio, 0.23; pre-test probability, 2.13; and post-test probability, 82.
      CONCLUSIONS: CPB is useful in clinical practice as a diagnostic test, because
      there is an important change from pre-test to post-test probability.

PMID- 29340491
TI  - Survival in a cohort of patients with lung cancer: the role of age and gender in
      prognosis.
AB  - OBJECTIVE: To determine the demographic and clinical characteristics of patients
      with non-small cell lung cancer (NSCLC), as well as their disease course, by age
      group and gender. METHODS: This was a retrospective cohort study of patients
      diagnosed with NSCLC from 2000 to 2012 and followed until July 2015 in a tertiary
      referral hospital in the city of Sao Paulo, Brazil. Based on the 25th and 75th
      percentiles of the age distribution, patients were stratified into three age
      groups: < 55 years; >= 55 and < 72 years; and >= 72 years. Survival time was
      evaluated during the follow-up period of the study. Functions of overall and
      gender-specific survival stratified by age groups (event: all-cause mortality)
      were calculated using the Kaplan-Meier method. Differences among survival curves
      were assessed via the log-rank test. RESULTS: We included 790 patients with the
      following age distribution: < 55 years, 165 patients; >= 55 and < 72 years, 423;
      and >= 72 years, 202. In the entire sample, there were 493 men (62.4%).
      Adenocarcinoma was the most common histological pattern in the < 72-year age
      groups; 575 patients (73%) presented with advanced disease (stages IIIB-IV). The
      median 5-year survival was 12 months (95% CI: 4-46 months), with no significant
      differences among the age groups studied. CONCLUSIONS: NSCLC remains more common
      in men, although we found an increase in the proportion of the disease in women
      in the < 55-year age group. Adenocarcinoma predominated in women. In men,
      squamous cell carcinoma predominated in the >= 72-year age group. Most patients
      presented with advanced-stage disease at diagnosis. There were no statistical
      differences in survival between genders or among age groups.

PMID- 29340492
TI  - Evaluation of the impact that the changes in tuberculosis treatment implemented
      in Brazil in 2009 have had on disease control in the country.
AB  - OBJECTIVE: To analyze the impact that the 2009 changes in tuberculosis treatment
      in Brazil had on the rates of cure, tuberculosis recurrence, mortality, treatment
      abandonment, and multidrug-resistant tuberculosis (MDR-TB). METHODS: An ordinary
      least squares regression model was used in order to perform an interrupted time
      series analysis of secondary data collected from the Brazilian Tuberculosis Case
      Registry Database for the period between January of 2003 and December of 2014.
      RESULTS: The 2009 changes in tuberculosis treatment in Brazil were found to have
      no association with reductions in the total number of cases (beta = 2.17; 95% CI:
      -3.80 to 8.14; p = 0.47) and in the number of new cases (beta = -0.97; 95% CI: 
      5.89 to 3.94; p = 0.70), as well as having no association with treatment
      abandonment rates (beta = 0.40; 95% CI: -1.12 to 1.93; p = 0.60). The changes in
      tuberculosis treatment also showed a trend toward an association with decreased
      cure rates (beta = -4.14; 95% CI: -8.63 to 0.34; p = 0.07), as well as an
      association with increased mortality from pulmonary tuberculosis (beta = 0.77;
      95% CI: 0.16 to 1.38; p = 0.01). Although there was a significant increase in MDR
      TB before and after the changes (p < 0.0001), there was no association between
      the intervention (i.e., the changes in tuberculosis treatment) and the increase
      in MDR-TB cases. CONCLUSIONS: The changes in tuberculosis treatment were unable
      to contain the decrease in cure rates, the increase in treatment abandonment
      rates, and the increase in MDR-TB rates, being associated with increased
      mortality from pulmonary tuberculosis during the study period.Keywords:
      Tuberculosis, pulmonary/epidemiology; Tuberculosis, pulmonary/drug therapy;
      Tuberculosis, pulmonary/mortality; Interrupted time series analysis; Drug
      resistance, multiple; Drug compounding.

PMID- 29340493
TI  - Mortality from idiopathic pulmonary fibrosis: a temporal trend analysis in
      Brazil, 1979-2014.
AB  - OBJECTIVE: To analyze mortality from idiopathic pulmonary fibrosis (IPF) in
      Brazil over the period 1979-2014. METHODS: Microdata were extracted from the
      Brazilian National Ministry of Health Mortality Database. Only deaths for which
      the underlying cause was coded as International Classification of Diseases
      version 9 (ICD-9) 515 or 516.3 (until 1995) or as ICD version 10 (ICD-10) J84.1
      (from 1996 onward) were included in our analysis. Standardized mortality rates
      were calculated for the 2010 Brazilian population. The annual trend in mortality
      rates was analyzed by joinpoint regression. We calculated risk ratios (RRs) by
      age group, time period of death, and gender, using a person-years denominator.
      RESULTS: A total of 32,092 deaths were recorded in the study period. Standardized
      mortality rates trended upward, rising from 0.24/100,000 population in 1979 to
      1.10/100,000 population in 2014. The annual upward trend in mortality rates had
      two inflection points, in 1992 and 2008, separating three distinct time segments
      with an annual growth of 2.2%, 6.8%, and 2.4%, respectively. The comparison of
      RRs for the age groups, using the 50- to 54-year age group as a reference, and
      for the study period, using 1979-1984 as a reference, were 16.14 (14.44-16.36)
      and 6.71 (6.34-7.12), respectively. Men compared with women had higher
      standardized mortality rates (per 100,000 person-years) in all age groups.
      CONCLUSION: Brazilian IPF mortality rates are lower than those of other
      countries, suggesting underdiagnosis or underreporting. The temporal trend is
      similar to those reported in the literature and is not explained solely by
      population aging.

PMID- 29340494
TI  - Niemann-Pick disease type B: HRCT assessment of pulmonary involvement.
AB  - OBJECTIVE: To analyze HRCT findings in patients with Niemann-Pick disease (NPD)
      type B, in order to determine the frequency of HRCT patterns and their
      distribution in the lung parenchyma, as well as the most common clinical
      characteristics. METHODS: We studied 13 patients (3 males and 10 females) aged 5
      to 56 years. HRCT images were independently evaluated by two observers, and
      disagreements were resolved by consensus. The inclusion criteria were presence of
      abnormal HRCT findings and diagnosis of NPD type B confirmed by histopathological
      examination of a bone marrow, lung, or liver biopsy specimen. RESULTS: The most
      common clinical findings were hepatosplenomegaly and mild to moderate dyspnea.
      The most common HRCT patterns were smooth interlobular septal thickening and
      ground-glass opacities, which were both present in all patients. Intralobular
      lines were present in 12 patients (92.3%). A crazy-paving pattern was observed in
      5 patients (38.4%), and areas of air trapping were identified in only 1 case
      (7.6%). Pulmonary involvement was bilateral in all cases, with the most affected
      area being the lower lung zone. CONCLUSIONS: Smooth interlobular septal
      thickening, with or without associated ground-glass opacities, in patients with
      hepatosplenomegaly is the most common finding in NPD type B.

PMID- 29340495
TI  - Validation of the STOP-Bang questionnaire as a means of screening for obstructive
      sleep apnea in adults in Brazil.
AB  - OBJECTIVE: To validate the Portuguese-language version of the STOP-Bang (acronym
      for Snoring, Tiredness, Observed apnea, high blood Pressure, Body mass index,
      Age, Neck circumference, and Gender) questionnaire, culturally adapted for use in
      Brazil, as a means of screening for obstructive sleep apnea (OSA) in adults.
      METHODS: In this validation study, we enrolled patients >= 18 years of age,
      recruited between May of 2015 and November of 2016. All patients completed the
      STOP-Bang questionnaire and underwent overnight polysomnography. To evaluate the
      performance of the questionnaire, we used contingency tables and areas under the
      (receiver operating characteristic) curve (AUCs). RESULTS: We included 456
      patients. The mean age was 43.7 +/- 12.5 years, and 291 (63.8%) of the patients
      were male. On the basis of the apnea-hypopnea index (AHI), we categorized OSA as
      mild/moderate/severe (any OSA; AHI >= 5 events/h), moderate/severe (AHI >= 15
      events/h), or severe (AHI >= 30 events/h). The overall prevalence of OSA was
      78.3%, compared with 52.0%, and 28.5% for moderate/severe and severe OSA,
      respectively. The most common score on the STOP-Bang questionnaire was 4 points
      (n = 106), followed by 3 points (n = 85) and 5 points (n = 82). An increase in
      the score was paralleled by a reduction in sensitivity with a corresponding
      increase in specificity for all AHI cut-off points. The AUCs obtained for the
      identification of any, moderate/severe, and severe OSA were: 0.743, 0.731, and
      0.779, respectively. For any OSA, the score on the questionnaire (cut-off, >= 3
      points) presented sensitivity, specificity, and accuracy of 83.5%, 45.5%, and
      75.2%, respectively. CONCLUSIONS: The STOP-Bang questionnaire performed
      adequately for OSA screening, indicating that it could be used as an effective
      screening tool for the disorder.

PMID- 29340496
TI  - Effects of simple long-term respiratory care strategies in older men with COPD.
AB  - OBJECTIVE: To evaluate a 24-month supervised, community-based maintenance
      exercise program after 3 months of pulmonary rehabilitation (PR) in comparison
      with a 27-month physical activity counseling program, in terms of the effects on
      maximal muscle strength, muscle power output, and exercise capacity, in
      individuals with COPD. METHODS: Sixty-three men with moderate-to-severe COPD were
      recruited from two previous studies. Of those 63 participants, 31 were offered 3
      months of PR followed by a 24-month supervised maintenance exercise program
      (24MME group) and 32 were offered a 27-month physical activity counseling program
      (27MPAC group). Measurements at 3 months and at the end of the study period
      included maximal strength of the upper and lower limbs, power output of the lower
      limbs, six-minute walk distance (6MWD), and quality of life. RESULTS: At 27
      months, the improvements in maximal strength of the upper and lower limbs were
      greater in the 24MME group than in the 27MPAC group (37.6 +/- 28.3% and 28.4 +/-
      13.3%, respectively, vs. 8.8 +/- 16% and 13.6 +/- 16.4%, respectively; p < 0.05),
      as was the improvement in power output of the lower limbs (24.6 +/- 18.4% vs. 
      2.3 +/- 28.5%; p < 0.01). The increase in the 6MWD after 3 months was also
      greater in the 24MME group than in the 27MPAC group (33.2 +/- 36.6 m vs. 2.9 +/-
      34.7 m; p < 0.05), although there were no differences between the two groups in
      terms of the Delta6MWD at 27 months (vs. baseline). CONCLUSIONS: A supervised,
      community-based maintenance program is a successful long-term strategy to
      preserve the benefits of PR on peripheral muscle function and exercise capacity
      in individuals with COPD. However, physical activity counseling can maintain
      maximal muscle strength and exercise capacity in such individuals.

PMID- 29340498
TI  - Omalizumab in patients with severe uncontrolled asthma: well-defined eligibility
      criteria to promote asthma control.

PMID- 29340497
TI  - Tuberculosis treatment.
AB  - Tuberculosis treatment remains a challenge due to the need to consider, when
      approaching it, the context of individual and collective health. In addition,
      social and economic issues have been shown to be variables that need to be
      considered when it comes to treatment effectiveness. We conducted a critical
      review of the national and international literature on the treatment of
      tuberculosis in recent years with the aims of presenting health care workers with
      recommendations based on the situation in Brazil and better informing decision
      making regarding tuberculosis patients so as to minimize morbidity and interrupt
      disease transmission.

PMID- 29340499
TI  - Primary sclerosing epithelioid fibrosarcoma of the pleura.

PMID- 29340500
TI  - Respiratory evaluation through volumetric capnography among grade III obese and
      eutrophic individuals: a comparative study.
AB  - BACKGROUND: Excess trunk body fat in obese individuals influences respiratory
      physiological function. The aims of this study were to compare volumetric
      capnography findings (VCap) between severely obese patients and normal-weight
      subjects and to assess whether there is any association between neck
      circumference (NC), waist-hip ratio (WHR) and VCap among grade III obese
      individuals. DESIGN AND SETTING: Analytical observational case-matched cross
      sectional study, University of Campinas. METHODS: This cross-sectional study
      compared VCap variables between 60 stage III obese patients and 60 normal-weight
      individuals. RESULTS: In comparison with the normal-weight group, obese patients
      presented higher alveolar minute volume (8.92 +/- 4.94 versus 6.09 +/- 2.2; P = <
      0.0001), CO2 production (278 +/- 91.0 versus 209 +/- 60.23; P < 0.0001),
      expiratory tidal volume (807 +/- 365 versus 624 +/- 202; P = 0.005), CO2
      production per breath (21.1 +/- 9.7 versus 16.7 +/- 6.16; P = 0.010) and peak
      expiratory flow (30.9 +/- 11.9 versus 25.5 +/- 9.13; P = 0.004). The end
      expiratory CO2 (PetCO2) concentration (33.5 +/- 4.88 versus 35.9 +/- 3.79; P =
      0.013) and the phase 3 slope were normalized according to expired tidal volume
      (0.02 +/- 0.05 versus 0.03 +/- 0.01; P = 0.049) were lower in the obese group.
      CONCLUSIONS: The greater the NC was, the larger were the alveolar minute volume,
      anatomical dead space, CO2 production per minute and per breath and expiratory
      volume; whereas the smaller were the phase 2 slope (P2Slp), phase 3 slope (P3Slp)
      and pressure drop in the mouth during inspiration.

PMID- 29340501
TI  - Accidents involving motorcycles and potential years of life lost. An ecological
      and exploratory study.
AB  - CONTEXT AND OBJECTIVE: Traffic accidents have gained prominence as one of the
      modern epidemics that plague the world. The objective of this study was to
      identify the spatial distribution of potential years of life lost (PYLL) due to
      accidents involving motorcycles in the state of Sao Paulo, Brazil. DESIGN AND
      SETTING: Ecological and exploratory study conducted in Sao Paulo. METHODS: Data
      on deaths among individuals aged 20-39 years due to motorcycle accidents (V20-V29
      in the International Classification of Diseases, 10th revision) in the state of
      Sao Paulo in the years 2007-2011 were obtained from DATASUS. These data were
      stratified into a database for the 63 microregions of this state, according to
      where the motorcyclist lived. PYLL rates per 100,000 inhabitants were calculated.
      Spatial autocorrelations were estimated using the Global Moran index (IM).
      Thematic, Moran and Kernel maps were constructed using PYLL rates for the age
      groups of 20-29 and 30-39 years. The Terraview 4.2.2 software was used for the
      analysis. RESULTS: The PYLL rates were 486.9 for the ages of 20-29 years and
      199.5 for 30-39 years. Seventeen microregions with high PYLL rates for the age
      group of 20-29 years were identified. There was higher density of these rates on
      the Kernel map of the southeastern region (covering the metropolitan region of
      Sao Paulo). There were no spatial autocorrelations between rates. CONCLUSIONS:
      The data presented in this study identified microregions with high accident rates
      involving motorcycles and microregions that deserve special attention from
      regional managers and traffic experts.

PMID- 29340502
TI  - Recurrence of retroperitoneal localized perivascular epithelioid cell tumor two
      years after initial diagnosis: case report.
AB  - CONTEXT: Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal
      tumors. Adjuvant radiotherapy and/or chemotherapy are administered according to
      the patient's clinical characteristics. CASE REPORT: A 42-year-old female patient
      was operated to treat a retroperitoneal mass. The diagnosis was established as
      PEComa with benign behavior. Two years after the diagnosis, chest and abdominal
      computed tomography scans showed intra-abdominal recurrence and
      lymphangioleiomyomatosis in the lung. Treatment with everolimus was started. The
      disease stabilized in the third month of treatment, according to the response
      evaluation criteria in solid tumors. CONCLUSION: PEComas are tumors with
      unpredictable behavior. Therefore, these patients require long-term follow-up,
      even in cases of correct diagnosis and benign PEComa.

PMID- 29340503
TI  - Epidemiological situation of acquired immunodeficiency syndrome (AIDS)-related
      mortality in a municipality in northeastern Brazil. A retrospective cross
      sectional study.
AB  - CONTEXT AND OBJECTIVE: The number of acquired immunodeficiency syndrome (AIDS)
      related deaths covers different segments of the population differently, making
      monitoring of this mortality essential. The aim of this study was to describe the
      epidemiological situation of AIDS-related mortality in a municipality in the
      northeastern region of Brazil. DESIGN AND SETTING: Retrospective cross-sectional
      study based on data from death certificates in the mortality information system
      of the Health Information Center, Municipal Health Foundation, Brazil. METHODS:
      Between 2003 and 2013, we investigated death certificates on which AIDS-related
      mortality was reported. Sociodemographic data, year, place, type of establishment
      where death occurred and underlying and associated causes that led to AIDS
      related death were described. The Mann-Kendall test was used to verify the growth
      trend of the standardized mortality rate over the period studied. RESULTS: Among
      the 1,066 AIDS-related deaths, 69.7% were among men; 47.2% of the individuals
      were 28-41 years of age, 32.7% had had 4-7 years of schooling, 66.9% were pardos
      (mixed race), 55.7% were unmarried and 15.3% were housekeepers. Hospitals were
      the site of 97% of the deaths, and 91% occurred at public hospitals. Respiratory
      failure was the main cause of death. The prevalence of infectious and parasitic
      diseases was 99.0%. AIDS-related mortality increased by 160% over the period
      studied, from 5.5/100,000 inhabitants in 2003 to 14.3/100,000 in 2013.
      CONCLUSION: In the Brazilian municipality studied here, AIDS-related mortality
      was most prevalent among men and young adults of lower socioeconomic level. Over
      the period studied, the mortality rate increased.

PMID- 29340505
TI  - [Anthropology of Health in the Americas: Contextualizations and suggestions].

PMID- 29340504
TI  - Strategies to optimize MEDLINE and EMBASE search strategies for anesthesiology
      systematic reviews. An experimental study.
AB  - BACKGROUND: A high-quality electronic search is essential for ensuring accuracy
      and comprehensiveness among the records retrieved when conducting systematic
      reviews. Therefore, we aimed to identify the most efficient method for searching
      in both MEDLINE (through PubMed) and EMBASE, covering search terms with variant
      spellings, direct and indirect orders, and associations with MeSH and EMTREE
      terms (or lack thereof). DESIGN AND SETTING: Experimental study. UNESP, Brazil.
      METHODS: We selected and analyzed 37 search strategies that had specifically been
      developed for the field of anesthesiology. These search strategies were adapted
      in order to cover all potentially relevant search terms, with regard to variant
      spellings and direct and indirect orders, in the most efficient manner. RESULTS:
      When the strategies included variant spellings and direct and indirect orders,
      these adapted versions of the search strategies selected retrieved the same
      number of search results in MEDLINE (mean of 61.3%) and a higher number in EMBASE
      (mean of 63.9%) in the sample analyzed. The numbers of results retrieved through
      the searches analyzed here were not identical with and without associated use of
      MeSH and EMTREE terms. However, association of these terms from both controlled
      vocabularies retrieved a larger number of records than did the use of either one
      of them. CONCLUSIONS: In view of these results, we recommend that the search
      terms used should include both preferred and non-preferred terms (i.e. variant
      spellings and direct/indirect order of the same term) and associated MeSH and
      EMTREE terms, in order to develop highly-sensitive search strategies for
      systematic reviews.

PMID- 29340507
TI  - [Health care practices among people living with diabetes: an anthropological,
      ethnographical approach with a gender perspective].
AB  - Diabetes, a disease that constitutes a syndrome, is growing more quickly in
      societies with precarious living and working conditions. Daily care practices are
      fundamental in preventing it from progressing. This work shows the heuristic and
      interpretative value and the explanatory potential of an ethnographic approach
      and a gender perspective in the analysis of care practices in a group of elder
      adults living with type 2 diabetes. The research was carried out with diabetes
      group participants and health professionals in a primary healthcare center in
      Jose Leon Suarez, municipality of San Martin, province of Buenos Aires, during
      the period 2013-2016. We identified and analyzed care activities (including self
      care) that resulted from the authoritative knowledge of the group in connection
      with the healthcare center professionals. Such individual, group and collective
      actions generate care logics that promote care of oneself. The methodological
      proposal of this study is framed within the tradition of collaborative fieldwork.

PMID- 29340506
TI  - [On ethnographic positions in the anthropology of health in South America].
AB  - Ethnographies on health issues in populations that live in conditions of poverty,
      inequality and segregation have proliferated over the last decades in South
      America. The aim of this article is to problematize - preliminarily - certain
      patterns in the positions and relations of ethnographers with respect to study
      subjects and populations during their fieldwork and in the writing of study
      results. This paper examines the relationships between these ethnographic
      positions and the dominant theoretical perspectives in the region. In addition,
      this article explores briefly the resolution power as well as the sensibilities,
      theoretical maps, and meanings of such positions in light of power logics,
      symbolic economies, and diverse manners of accumulation by dispossession in this
      geographical area.

PMID- 29340508
TI  - [Space, time and power in hospital health care: Contributions based on the
      ethnography of an obstetric center].
AB  - This paper presents the results of an ethnographic study of an obstetric center
      within a hospital of Greater Buenos Aires and an analysis of the spatio-temporal
      dimension of hospital care. The fieldwork, carried out between 2007 and 2011,
      followed the everyday dynamics of the hospital and included observation in the
      obstetrics unit (waiting areas, the obstetric center where births and emergencies
      receive care, and the ambulatory care, ultrasound, and hospitalization rooms,
      among others) as well as spaces such as the appointments and statistics offices,
      the office of social services, the central hall, the pharmacy, and hallway
      waiting areas. Interviews were carried out with department heads, obstetricians,
      nurses, social workers, staff of the laboratory and the appointment and
      statistics offices, volunteers and patients. In this way, the article analyzes
      the medical-bureaucratic routines in the admission and hospitalization of women
      in the obstetrics center; the disputes, transactions and negotiations occurring
      among professionals, patients and families; the delimitation of spaces; and the
      temporal sequences and hierarchies involved in the passage from the "outside" to
      the "inside" of the hospital.

PMID- 29340509
TI  - Uncovering a tragic flaw in revolutionary health policies: From health and
      communicative inequities to communicative justice in health.
AB  - This article analyzes a contradiction facing efforts by left-leaning governments
      in Latin America to transform health into a fundamental social right. Policies
      and practices that confront health inequities generally fail to address
      health/communicative inequities, hierarchical distributions of rights to shape
      what counts as legitimate knowledge of health. This ethnographic analysis focuses
      on an epidemic of a mysterious disease - identified clinically as bat-transmitted
      rabies - in the Delta Amacuro rainforest of Venezuela in 2007-2008, tracing how
      parents who lost 1-3 children faced acute health/communicative inequities in
      clinical settings, epidemiological investigations, work with healers, news
      coverage, health policy, and health communication. Taking as a point of departure
      rainforest residents' demands for communicative justice in health, the analysis
      draws on Menendez's notion of autoatencion in exploring how health/communicative
      labor is co-produced with the labor of care.

PMID- 29340510
TI  - [Tradition, improvisation and modernity in Yucatecan Mayan shamanism: The suhuy
      art of Juan Cob, h-men of Yaxcaba].
AB  - Through the history of a Yucatecan Mayan shaman (h-men), this article analyzes
      the changes and continuities in Yucatecan shamanism and, more specifically, in
      one of its main functions: tsak, healing. The results presented here are part of
      fieldwork carried out over 40 years, from 1976 to 2016. The author lives in a
      community in central Yucatan (Tabi, Sotuta) and has carried out a number of
      research studies on Yucatecan shamanism in communities in the Mexican states of
      Yucatan, Campeche and Quintana Roo. Juan Cob, h-men of Yaxcaba, is not only an
      informant but also the author's friend and neighbor, with whom he has created a
      number of films.

PMID- 29340511
TI  - [A critical examination of public policies related to indigenous health,
      traditional medicine, and interculturality in Mexico (1990-2016)].
AB  - Over the last 26 years, the Mexican government has developed a number of
      activities and discourses around what has been called "intercultural health,"
      directed especially at indigenous peoples in Mexico (some 62, according to
      linguistic criteria). In this way, the government has built health care
      institutions (rural centers, clinics, and hospitals) in states like Puebla,
      Nayarit, Oaxaca, Chiapas, Queretaro, and Jalisco, proposing the implementation of
      cultural pertinence indicators (which are minimal and inadequate). Nevertheless,
      the health conditions among indigenous populations and the quality of health care
      provided by public institutions continue to be precarious in terms of human and
      material resources (health personnel, drugs, etc.) and discriminatory with
      respect to the form and content of the provided services. This paper describes
      some of the governmental interventions that purport to be institutional
      improvements in the field of interculturality, but that actually represent the
      continuity of arbitrary and exclusive policies.

PMID- 29340512
TI  - Articulation between health services and "indigenous medicine": Anthropological
      reflections on policies and reality in Brazil.
AB  - This paper contributes to the dialogue between the social sciences and social
      medicine in Latin America by exploring therapeutic pluralism in indigenous health
      policies and services in Brazil. It reviews recent anthropological research,
      concepts and current debates to critically examine Brazilian indigenous health
      policy and its concept of "differentiated care," which proposes articulation
      between official health practices and indigenous therapies. A number of
      contradictions and tensions are present in the structural organizational of the
      indigenous health subsystem at the national level and in the daily practices of
      health teams at the local level. Guided by the hegemonic ideology of biomedicine,
      health professionals fail to recognize the dynamics and agency expressed in
      indigenous health practices.

PMID- 29340513
TI  - [Family networks and the role of men in maternal health care among Mexican
      indigenous women].
AB  - This article reflects on maternal mortality among indigenous women in Mexico and
      the changes that have occurred in care practices during pregnancy and childbirth.
      Through ethnographic qualitative research in the state of Guerrero between 2008
      and 2012, which included over a year of fieldwork as well as in-depth interviews
      and surveys with indigenous women, the article analyzes the increasing
      medicalization of reproduction, the role of family networks in gestation,
      delivery and postpartum care, and the participation of men during childbirth, in
      dialogue with other anthropological research on maternal health in Mexico.
      Medical anthropology allows us to understand the medicalization of reproduction
      in indigenous contexts and identify the tension that characterizes family care
      networks, which both operate as protectors and mobilizers in seeking care and
      reproduce power relations marked by gender and generational conditions.

PMID- 29340514
TI  - Racial i(nter)dentification: The racialization of maternal health through the
      Oportunidades program and in government clinics in Mexico.
AB  - Using an ethnographic approach, this article examines the role of racialization
      in health-disease-care processes specifically within the realm of maternal
      health. It considers the experiences of health care administrators and providers,
      indigenous midwives and mothers, and recipients of conditional cash transfers
      through the Oportunidades program in Mexico. By detailing the delivery of
      trainings of the Mexican Social Security Institute (IMSS) [Instituto Mexicano del
      Seguro Social] for indigenous midwives and Oportunidades workshops to indigenous
      stipend recipients, the article critiques the deployment of "interculturality" in
      ways that inadvertently re-inscribe inequality. The concept of racial
      i(nter)dentification is offered as a way of understanding processes of
      racialization that reinforce discrimination without explicitly referencing race.
      Racial i(nter)dentification is a tool for analyzing the multiple variables
      contributing to the immediate mental calculus that occurs during quotidian
      encounters of difference, which in turn structures how individuals interact
      during medical encounters. The article demonstrates how unequal sociohistorical
      and political conditions and differential access to economic resources become
      determinants of health.

PMID- 29340515
TI  - [Illegitimate patients: Undocumented immigrants' access to health care in Chile].
AB  - In recent decades, Chile has become a destination for immigrants from other South
      American countries, which has significantly impacted public services -
      particularly the public health system - at the economic, social, and cultural
      levels. The aim of this paper is to provide substantiated information on issues
      concerning undocumented immigrants' access to health care in Chile. A qualitative
      methodology, fundamentally an ethnography of the clinical setting, was used.
      Results were then analyzed in relation to theories of power asymmetries and
      interethnic relations. The research results highlight the lack of compliance with
      existing regulations and the exercise of discretionary personal judgment as
      barriers to access. It is concluded that in Chile immigrants in general, and
      undocumented immigrants in particular, are considered to be illegitimate
      patients.

PMID- 29340516
TI  - [Screening program for cervical cancer: public policies and experiences of actors
      who implement the program in the state of Veracruz, Mexico].
AB  - The aim of this article is to analyze the way in which the Screening Program for
      Cervical Cancer is carried out in a dysplasia clinic and related health centers
      in the state of Veracruz, through the representations and practices of the social
      actors who implement the program. In order to do so, in-depth interviews and
      observations of the practices of health service providers were carried out during
      different periods over the course of three years, from 2009 to 2011. Through the
      information obtained, the article explores the difficulties, achievements and
      results of this program as part of a public policy. Although a priority of public
      health policy is to see the whole population benefit from preventive and curative
      health care services, evidence shows that marginalized populations are not
      benefitted by such programs; such information does not however seem to permeate
      popular and medical knowledge.

PMID- 29340517
TI  - [Indigenous peoples, HIV and public policy in Latin America: an exploration of
      the current situations of epidemiological prevalence, prevention, care and timely
      treatment].
AB  - This article aims to describe and analyze the situations of epidemiological
      prevalence, prevention, care and treatment of HIV in indigenous populations of
      Latin America. In order to do so, 304 published materials - including
      declarations, public policy and health program protocols, case studies and
      literature reviews with local, national and regional scopes - were identified,
      classified and analyzed. The differential social vulnerability to HIV infection
      and the inequity in health care access among indigenous populations can be
      attributed to the juxtaposition of factors such as structural violence, gender,
      racism, and discrimination due health condition (living with HIV) as well as the
      subordinated position of indigenous peoples in societies stratified not only
      socially and economically but also ethnically and culturally. The few studies
      done in the region on epidemiological prevalence, morbidity and mortality that
      are disaggregated by ethnicity reveal alarming data highlighting the need for
      further information on the epidemic in this population so as to address its
      repercussions in terms of prevention, care and timely follow-up.

PMID- 29340518
TI  - Rankl expression predicts poor prognosis in gastric cancer patients: results from
      a retrospective and single-center analysis.
AB  - The receptor activator of nuclear factor kappaB ligand (RANKL)/RANK pathway plays
      an important role in the prognosis of several solid tumor types, but its role in
      gastric cancer prognosis has been poorly characterized. A total of 116 gastric
      cancer patients who underwent surgical resection were enrolled in this study.
      Expressions of RANKL and RANK in gastric cancer tissues were detected using
      immunohistochemical staining. Thirty-eight patients (33%) showed a high level of
      RANKL expression and 61 patients (53%) showed a high level of RANK expression.
      There was a positive correlation between expressions of RANKL and RANK (P=0.014,
      r=0.221). A high level of RANKL expression indicated shorter overall survival
      (OS) (P=0.008), and was associated with a higher pathological tumor/lymph
      node/metastasis (pTNM) stage (P=0.035), while no significant correlation was
      detected between RANK expression and clinicopathological parameters. RANKL also
      predicted poor prognosis in patients with high RANK expression (P=0.008) and
      Bormann's type III/IV (P=0.002). Furthermore, RANKL expression correlated with
      pTNM stage according to high RANK expression (P=0.009), while no significance was
      found in patients with low RANK expression (P=1.000). Together, our results
      revealed that high expression of RANKL could predict worse outcomes in gastric
      cancer especially combined with RANK detection, and thereby this pathway could be
      a useful prognostic indicator of gastric cancer.

PMID- 29340519
TI  - Evaluating the current state of the art of Huntington disease research: a
      scientometric analysis.
AB  - Huntington disease (HD) is an incurable neurodegenerative disorder caused by a
      dominant mutation on the 4th chromosome. We aim to present a scientometric
      analysis of the extant scientific undertakings devoted to better understanding
      HD. Therefore, a quantitative study was performed to examine the current state-of
      the-art approaches that foster researchers' understandings of the current
      knowledge, research trends, and research gaps regarding this disorder. We
      performed literature searches of articles that were published up to September
      2016 in the "ISI Web of ScienceTM" (http://apps.webofknowledge.com/). The keyword
      used was "Huntington disease". Of the initial 14,036 articles that were obtained,
      7732 were eligible for inclusion in the study according to their relevance. Data
      were classified according to language, country of publication, year, and area of
      concentration. The country leader regarding the number of studies published on HD
      is the United States, accounting for nearly 30% of all publications, followed by
      England and Germany, who have published 10 and 7% of all publications,
      respectively. Regarding the language in which the articles were written, 98% of
      publications were in English. The first publication to be found on HD was
      published in 1974. A surge of publications on HD can be seen from 1996 onward. In
      relation to the various knowledge areas that emerged, most publications were in
      the fields of neuroscience and neurology, likely because HD is a
      neurodegenerative disorder. Publications written in areas such as psychiatry,
      genetics, and molecular biology also predominated.

PMID- 29340520
TI  - Analysis of serum microRNA expression in male workers with occupational noise
      induced hearing loss.
AB  - Occupational noise-induced hearing loss (ONIHL) is a prevalent occupational
      disorder that impairs auditory function in workers exposed to prolonged noise.
      However, serum microRNA expression in ONIHL subjects has not yet been studied. We
      aimed to compare the serum microRNA expression profiles in male workers of ONIHL
      subjects and controls. MicroRNA microarray analysis revealed that four serum
      microRNAs were differentially expressed between controls (n=3) and ONIHL subjects
      (n=3). Among these microRNAs, three were upregulated (hsa-miR-3162-5p, hsa-miR
      4484, hsa-miR-1229-5p) and one was downregulated (hsa-miR-4652-3p) in the ONIHL
      group (fold change >1.5 and Pbon value <0.05). Real time quantitative PCR was
      conducted for validation of the microRNA expression. Significantly increased
      serum levels of miR-1229-5p were found in ONIHL subjects compared to controls
      (n=10 for each group; P<0.05). A total of 659 (27.0%) genes were predicted as the
      target genes of miR-1229-5p. These genes were involved in various pathways, such
      as mitogen-activated protein kinase (MAPK) signaling pathway. Overexpression of
      miR-1229-5p dramatically inhibited the luciferase activity of 3' UTR segment of
      MAPK1 (P<0.01). Compared to the negative control, HEK293T cells expressing miR
      1229-5p mimics showed a significant decline in mRNA levels of MAPK1 (P<0.05).
      This preliminary study indicated that serum miR-1229-5p was significantly
      elevated in ONIHL subjects. Increased miR-1229-5p may participate in the
      pathogenesis of ONIHL through repressing MAPK1 signaling.

PMID- 29340521
TI  - Organic solvent exposure and contrast sensitivity: comparing men and women.
AB  - The goal of this study was to compare the visual contrast sensitivity (CS) of men
      and women exposed and not exposed to organic solvents. Forty-six volunteers of
      both genders aged between 18 and 41 years (mean+/-SD=27.72+/-6.28) participated.
      Gas station attendants were exposed to gas containing 46.30 ppm of solvents at a
      temperature of 304+/-274.39 K, humidity of 62.25+/-7.59% and ventilation of
      0.69+/-0.46 m/s (a passive gas chromatography-based sampling method was used
      considering the microclimate variables). Visual CS was measured via the
      psychophysical method of two-alternative forced choice using vertical sinusoidal
      gratings with spatial frequencies of 0.2, 0.5, 1.0, 2.0, 5.0, 10.0, and 16.0 cpd
      (cycles per degree) and an average luminance of 34.4 cd/m2. The results showed
      that visual CS was significantly lower (P<0.05) in the following groups: i)
      exposed men compared to unexposed men at frequencies of 0.2, 0.5, 1.0, and 2.0
      cpd; ii) exposed women compared to unexposed women at a frequency of 5.0 cpd; and
      iii) exposed women compared to exposed men at a frequency of 0.5 cpd, even at
      exposures below the tolerance limit (300 ppm). These results suggest that the
      visual CS of exposed men was impaired over a wider range of spatial frequencies
      than that of exposed women. This difference may have been due to the higher body
      fat content of women compared to that of men, suggesting that body fat in women
      can serve as a protective factor against neurotoxic effects.

PMID- 29340522
TI  - Penile microvascular endothelial function in hypertensive patients: effects of
      acute type 5 phosphodiesterase inhibition.
AB  - The primary aim of this study was to evaluate penile endothelial microvascular
      function in patients with primary arterial hypertension and age-matched
      normotensive subjects using laser speckle contrast imaging (LSCI). Additionally,
      we analyzed the acute penile microvascular effects induced by oral
      phosphodiesterase type 5 inhibitor (sildenafil; SIL) administration. Endothelium
      dependent microvascular reactivity was evaluated in the penises and forearms of
      hypertensive patients (aged 58.8+/-6.6 years, n=34) and age-matched healthy
      volunteers (n=33) at rest and 60 min following oral SIL (100 mg) administration.
      LSCI was coupled with cutaneous acetylcholine (ACh) iontophoresis using
      increasing anodal currents. Basal penile cutaneous vascular conductance (CVC)
      values were not significantly different between control subjects and hypertensive
      individuals. Penile CVC values increased significantly after SIL administration
      in control (P<0.0001) and hypertensive (P<0.0001) subjects. Peak CVC values were
      not different between the two groups during penile ACh iontophoresis before SIL
      administration (P=0.2052). Peak CVC values were higher in control subjects than
      in hypertensive subjects after SIL administration (P=0.0427). Penile endothelium
      dependent microvascular function is, to some extent, preserved in patients
      presenting with primary arterial hypertension under effective anti-hypertensive
      treatment. LSCI may be a valuable non-invasive tool for the evaluation of penile
      vascular responses to phosphodiesterase type 5 inhibitor.

PMID- 29340523
TI  - A case of severe glutathione synthetase deficiency with novel GSS mutations.
AB  - Glutathione synthetase deficiency (GSSD) is a rare inborn error of glutathione
      metabolism with autosomal recessive inheritance. The severe form of the disease
      is characterized by acute metabolic acidosis, usually present in the neonatal
      period with hemolytic anemia and progressive encephalopathy. A case of a male
      newborn infant who had severe metabolic acidosis with high anion gap, hemolytic
      anemia, and hyperbilirubinemia is reported. A high level of 5-oxoproline was
      detected in his urine and a diagnosis of generalized GSSD was made. DNA sequence
      analysis revealed the infant to be compound heterozygous with two mutations,
      c.738dupG in exon 8 of GSS gene resulting in p.S247fs and a repetitive sequence
      in exon 3 of GSS gene. Treatment after diagnosis of GSSD included supplementation
      with antioxidants and oral sodium hydrogen bicarbonate. However, he maintained a
      variable degree of metabolic acidosis and succumbed shortly after his parents
      requested discontinuation of therapy because of dismal prognosis and medical
      futility when he was 18 days old.

PMID- 29340524
TI  - Efficacy of removal of cariogenic bacteria and carious dentin by ablation using
      different modes of Er:YAG lasers.
AB  - The primary objective of this in vitro study was to evaluate the efficiency of
      removal of cariogenic bacteria and carious dentin by ablation using two lasers:
      fluorescence-feedback controlled (FFC) Er:YAG laser and different pulses of
      Er:YAG laser based on variable square pulse technology (VSPt). The secondary
      objective was to measure the temperature during laser ablation of carious tissue.
      Seventy-two extracted human molars were used in this study. Sixty teeth with
      carious dentin were randomly divided into four experimental groups according to
      the treatment for caries removal: group 1: 400 us (FFC group); group 2: super
      short pulse (SSP group, 50 us pulse); group 3: medium short pulse (MSP group, 100
      us pulse); group 4: short pulse (SP group, 300 us pulse) and one positive control
      group with no treatment. Twelve teeth without carious lesion were used as a
      negative control group. After caries removal, swabs were taken with cotton
      pellets and real-time PCR analysis was performed. During caries ablation, a
      thermal infrared camera was used to measure the temperature changes. In all
      experimental groups, specimens were free of bacterial contamination after the
      treatment. In the SSP, MSP and SP groups, temperatures measured during caries
      ablation were significantly higher compared to temperatures in the FFC group
      (P<0.001). In this in vitro study, laser treatment for removal of carious dentin
      and cariogenic bacteria was an efficient treatment modality without causing
      excessive temperatures that might adversely affect pulp vitality.

PMID- 29340525
TI  - Time collection and storage conditions of lipid profile.
AB  - The stability of samples is crucial for getting reliable concentrations of many
      analytes, including lipid profile. Thus, the goal of this study was to analyze
      lipid profile under different storage and temperature conditions. This was a
      prospective study with 809 patients of both genders. Total cholesterol,
      triglycerides, high-density lipoprotein cholesterol, low density lipoprotein
      cholesterol and non-high-density lipoprotein were measured within 1 h from
      collection at room temperature, after 2-3 h of refrigeration (8 degrees C) and
      after 4-5 h at room temperature. The processing time and storage conditions did
      not affect the analytes measured. These findings are important for multicenter
      studies, because of the difficulties related to centrifugation and freezing of
      samples immediately after collection.

PMID- 29340526
TI  - Simulating the behavior of patients who leave a public hospital emergency
      department without being seen by a physician: a cellular automaton and agent
      based framework.
AB  - The objective of this study was to develop an agent based modeling (ABM)
      framework to simulate the behavior of patients who leave a public hospital
      emergency department (ED) without being seen (LWBS). In doing so, the study
      complements computer modeling and cellular automata (CA) techniques to simulate
      the behavior of patients in an ED. After verifying and validating the model by
      comparing it with data from a real case study, the significance of four
      preventive policies including increasing number of triage nurses, fast-track
      treatment, increasing the waiting room capacity and reducing treatment time were
      investigated by utilizing ordinary least squares regression. After applying the
      preventing policies in ED, an average of 42.14% reduction in the number of
      patients who leave without being seen and 6.05% reduction in the average length
      of stay (LOS) of patients was reported. This study is the first to apply CA in an
      ED simulation. Comparing the average LOS before and after applying CA with actual
      times from emergency department information system showed an 11% improvement. The
      simulation results indicated that the most effective approach to reduce the rate
      of LWBS is applying fast-track treatment. The ABM approach represents a flexible
      tool that can be constructed to reflect any given environment. It is also a
      support system for decision-makers to assess the relative impact of control
      strategies.

PMID- 29340527
TI  - Cardiac protein expression patterns are associated with distinct inborn exercise
      capacity in non-selectively bred rats.
AB  - In the present study, we successfully demonstrated for the first time the
      existence of cardiac proteomic differences between non-selectively bred rats with
      distinct intrinsic exercise capacities. A proteomic approach based on two
      dimensional gel electrophoresis coupled to mass spectrometry was used to study
      the left ventricle (LV) tissue proteome of rats with distinct intrinsic exercise
      capacity. Low running performance (LRP) and high running performance (HRP) rats
      were categorized by a treadmill exercise test, according to distance run to
      exhaustion. The running capacity of HRPs was 3.5-fold greater than LRPs. Protein
      profiling revealed 29 differences between HRP and LRP rats (15 proteins were
      identified). We detected alterations in components involved in metabolism,
      antioxidant and stress response, microfibrillar and cytoskeletal proteins.
      Contractile proteins were upregulated in the LVs of HRP rats (alpha-myosin heavy
      chain-6, myosin light chain-1 and creatine kinase), whereas the LVs of LRP rats
      exhibited upregulation in proteins associated with stress response (aldehyde
      dehydrogenase 2, alpha-crystallin B chain and HSPbeta-2). In addition, the
      cytoskeletal proteins desmin and alpha-actin were upregulated in LRPs. Taken
      together, our results suggest that the increased contractile protein levels in
      HRP rats partly accounted for their improved exercise capacity, and that proteins
      considered risk factors to the development of cardiovascular disease were
      expressed in higher amounts in LRP animals.

PMID- 29340528
TI  - Synthesis and anti-myocarditis activity in a multifunctional lanthanide
      microporous metal-organic framework with 1D helical chain building units.
AB  - A new microporous lanthanide metal-organic framework, {[Yb(BTB)(H2O) (DEF)2}n (1,
      DEF=N,N-Diethylformamide), with 1D nano-sized channels has been constructed by
      bridging helical chain secondary building units with 1,3,5-benzenetrisbenzoic
      acid (H3BTB) ligand. Structural characterization suggests that this complex
      crystallizes in the hexagonal space group P6122 and possesses 1D triangular
      channels with coordinated water molecules pointing to the channel center. In
      addition, anti-myocarditis properties of compound 1 were evaluated in vivo. The
      results showed that compound 1 can improve hemodynamic parameters of, and it may
      be a good therapeutic option for heart failure in the future.

PMID- 29340529
TI  - Association between syndecan-1 and renal function in adolescents with excess
      weight: evidence of subclinical kidney disease and endothelial dysfunction.
AB  - Excess weight (overweight and obesity) is associated with kidney and
      cardiovascular disease. The aim of this study was to investigate the association
      between syndecan-1 and renal function among adolescents with excess weight. A
      total of 56 students from a public school at Fortaleza, CE, Brazil, were
      investigated. The adolescents were submitted to anthropometric evaluation,
      including weight, height, blood pressure and body mass index. Blood and urine
      samples were collected for the determination of serum lipids (total cholesterol,
      high density lipoprotein cholesterol, low density lipoprotein cholesterol,
      triglycerides), and the endothelial injury biomarker syndecan-1. Participants'
      mean age was 16+/-1 years (range 14-19 years), and 68% were females. Overweight
      was observed in 4 cases (7.1%) and obesity in 7 (12.5%). Changes in serum lipid
      levels were more frequent in the overweight group. A positive correlation between
      syndecan-1 and serum creatinine (r=0.5, P=0.001) and triglycerides (r=0.37,
      P=0.004), and a negative correlation with glomerular filtration rate (r=-0.33,
      P=0.02) were found. These findings suggest that adolescents with excess weight
      present incipient changes at the cellular level that make them more vulnerable to
      the development of kidney and cardiovascular diseases.

PMID- 29340530
TI  - The use of biosimilar medicines in oncology - position statement of the Brazilian
      Society of Clinical Oncology (SBOC).
AB  - A biosimilar is a biologic product that is similar to a reference
      biopharmaceutical product, the manufacturing process of which hinders the ability
      to identically replicate the structure of the original product, and therefore, it
      cannot be described as an absolute equivalent of the original medication. The
      currently available technology does not allow for an accurate copy of complex
      molecules, but it does allow the replication of similar molecules with the same
      activity. As biosimilars are about to be introduced in oncology practice, these
      must be evaluated through evidence-based medicine. This manuscript is a position
      paper, where the Brazilian Society of Clinical Oncology (SBOC) aims to describe
      pertinent issues regarding the approval and use of biosimilars in oncology. As a
      working group on behalf of SBOC, we discuss aspects related to definition,
      labeling/nomenclature, extrapolation, interchangeability, switching, automatic
      substitution, clinical standards on safety and efficacy, and the potential impact
      on financial burden in healthcare. We take a stand in favor of the introduction
      of biosimilars, as they offer a viable, safe, and cost-effective alternative to
      the biopharmaceutical products currently used in cancer. We hope this document
      can provide valuable information to support therapeutic decisions that maximize
      the clinical benefit for the thousands of cancer patients in Brazil and can
      contribute to expedite the introduction of this new drug class in clinical
      practice. We expect the conveyed information to serve as a basis for further
      discussion in Latin America, this being the first position paper issued by a
      Latin American Oncology Society.

PMID- 29340531
TI  - Prenatal development of the sound transmitting apparatus in different embryonic
      stages of Malpolon monsspesulanus (squamata-serpentes).
AB  - The developmental investigation of sound transmitting apparatus is important in
      understanding the ontogenetic processes behind morphological diversity. The
      development of sound conducting apparatus was studied in Montpellier snake;
      Malpolon monspessulanus at 6.5, 7.2, 8.3 and 9.3 cm total body lengths using
      light microscopy study. The columella auris firstly appeared as undifferentiated
      rod shape mesenchymal cells. As the growth proceeded, it chondrified and
      differentiates into two main parts. In addition, the viscerocranium components
      which participate in formation of sound transmitting apparatus undergo critical
      organization. In more advanced stages, procartilagenous stylohyal chondrified and
      fuse with the well organized quadrate. These data considered as a base for
      functional and molecular mechanisms of sound transmitting apparatus studies and
      identification of diseases that may infect them.

PMID- 29340532
TI  - Effects of light-dark cycle on the spatial distribution and feeding activity of
      fish larvae of two co-occurring species (Pisces: Hypophthalmidae and Sciaenidae)
      in a Neotropical floodplain lake.
AB  - Most studies on mechanisms regulating fish larvae processes have focused on
      assessing the isolated effects of food distribution and feeding behavior.
      However, in natural ecosystems, fish larvae may strongly interact with
      zooplankton organisms in an array of complex, direct and indirect
      interdependencies. This study analyzed the spatial distribution, diet and feeding
      behavior of early stages of Hypophthalmus edentatus and Plagioscion
      squamosissimus, two fish species co-occurring in an isolated floodplain lake,
      during the light-dark cycle. Larvae fed more actively during dark periods (dusk
      and night) when they migrated toward the surface of the lake, and remained on the
      bottom and fed less during light periods (day and dawn). Cladocerans represented
      the most frequent prey in the diet of H. edentatus larvae. In turn, P.
      squamosissimus larvae initially preferred cladocerans and, as they developed,
      included calanoid copepods in the diet. Significant differences were detected in
      the frequencies of food items consumed during larval development, which could be
      related to a better ability of the most developed stages to explore the
      environment in search of other prey.

PMID- 29340533
TI  - More than two decades after the introduction of Limnoperna fortunei (Dunker 1857)
      in La Plata Basin.
AB  - The golden mussel, Limnoperna fortunei, is an Asian freshwater bivalve introduced
      in South America in the beginning of the 1990's, probably through ballast water
      releases in La Plata River estuary. It dispersed north through Parana, Uruguay
      and Paraguay Rivers. The study evaluated the macroscale (18 degrees  to 34
      degrees  S; 45 degrees  to 60 degrees  W) distribution of L. fortunei (larval
      stages) in the main rivers and reservoirs of La Plata Basin. Samplings were
      performed through 68 um vertical plankton net hauls. Limnological variables were
      simultaneously determined. Larvae abundance correlated significantly with oxygen
      (positively) in summer, with temperature (positively) in winter and with total
      phosphorus and total nitrogen (both negatively) in winter. We expected densities
      to decrease towards north (latitudinal gradient) and increase in lentic
      conditions (reservoirs). Despite maximum density was found near the introduction
      point (La Plata River) similar value was also observed 2,000 km north (Paraguay
      River). The first hypothesis was refuted. The second hypothesis was partially
      accepted. Abundances were consistently higher in summer. Higher trophic
      conditions and fast flow seem to inhibit population growth. Food resources
      (chlorophyll a) locally influenced temporal variation. Limnoperna fortunei is
      widely distributed in La Plata basin, reaching high larval densities superior to
      10,000 ind. m-3, in all major sub-basins. The species exhibits a high intrinsic
      dispersal ability (free planktonic larvae), wide tolerance to environmental
      factors and dispersion is potentialized by natural dispersion processes (e.g.
      fauna displacement) and human facilitation (e.g. commercial navigation).

PMID- 29340534
TI  - What every intensivist should know about intensive care unit admission criteria.

PMID- 29340535
TI  - Prevalence of cytomegalovirus disease in kidney transplant patients in an
      intensive care unit.
AB  - OBJECTIVES: To define the frequency of cytomegalovirus disease among kidney
      transplant patients in an intensive care unit in which this complication was
      suspected and to identify predisposing factors and their possible impact on
      clinical outcome. METHODS: Retrospective observational study in which kidney
      transplant patients over the age of 18 years were hospitalized for any reason in
      an intensive care unit with at least one collection of samples to test for the
      presence of antigenemia or cytomegalovirus via polymerase chain reaction during
      hospitalization. Cytomegalovirus disease was defined as positive antigenemia or
      polymerase chain reaction above 500 copies/mL in the presence of symptoms and in
      the appropriate clinical setting, as judged by the attending physician. RESULTS:
      A total of 99 patients were included (age: 53.4 +/- 12.8 years, 71.6% male).
      Cytomegalovirus disease was diagnosed in 39 patients (39.4%). Respiratory
      symptoms (51%), non-specific clinical worsening (20%) or gastrointestinal
      symptoms (14%) were the main reasons for exam collection. Transplant time was
      lower in those with cytomegalovirus disease than in those without this diagnosis
      (6.5 months and 31.2 months, p = 0.001), along with pulse therapy in the last 6
      months (41% and 16.9%, p = 0.008) and previous use of thymoglobulin in the last
      year (35.9% and 6.8%, p < 0.001). In the logistic regression model, only the
      transplant time and the use of thymoglobulin were associated with a higher
      frequency of cytomegalovirus. There was no difference in clinical evolution
      between patients with and without cytomegalovirus disease. CONCLUSION: In kidney
      transplant patients suspected of cytomegalovirus disease, the prevalence was
      high. Transplant time less than 6 months, and the use of thymoglobulin in the
      last year should increase the intensivist's suspicion for this complication.

PMID- 29340536
TI  - Assessment of PIM-2 performance among surgical patients with heart disease and
      correlation of results with RACHS-1.
AB  - OBJECTIVE: To assess the performance of the Pediatric Index of Mortality (PIM) 2
      and the Risk Adjustment for Congenital Heart Surgery (RACHS) in the postoperative
      period of congenital heart disease patients. METHODS: Retrospective cross
      sectional study. Data were collected from patient records to generate the scores
      and predictions using recommended techniques, demographic data and outcomes. The
      Mann-Whitney test, Hosmer-Lemeshow test, standardized mortality rate, area under
      the receiver operating characteristic (ROC) curve, chi square test, Poisson
      regression with robust variance and Spearman's test were used for statistical
      analysis. RESULTS: A total of 263 patients were evaluated, and 72 died (27.4%).
      These patients presented significantly higher PIM-2 values than survivors (p <
      0.001). In the RACHS-1 classification, mortality was progressively higher
      according to the complexity of the procedure, with a 3.24-fold increase in the
      comparison between groups 6 and 2. The area under the ROC curve for PIM-2 was
      0.81 (95%CI 0.75 - 0.87), while for RACHS-1, it was 0.70 (95%CI 0.63 - 0.77). The
      RACHS presented better calibration power in the sample analyzed. A significantly
      positive correlation was found between the results of both scores (rs = 0.532; p
      < 0.001). CONCLUSION: RACHS presented good calibration power, and RACHS-1 and PIM
      2 demonstrated good performance with regard to their discriminating capacities
      between survivors and non-survivors. Moreover, a positive correlation was found
      between the results of the two risk scores.

PMID- 29340537
TI  - Bedside ultrasound is a practical measurement tool for assessing muscle mass.
AB  - OBJECTIVE: To evaluate the intra- and inter-reliability and the ease of measuring
      the quadriceps muscle thickness using bedside ultrasound. METHODS: This is a
      prospective, observational study. The assessment of quadriceps muscle thickness
      was performed at two reference points and was quantified using portable B-mode
      ultrasound in two healthy volunteers. For standardization of measurements and
      validation of image collections, the team was trained through theoretical and
      practical classes, with a 6-hour workload. RESULTS: A total of 112 images were
      examined by the coach and compared with the trainees. Pearson's correlation
      analysis found an excellent relationship between the coach and all trainees (R2 >
      0.90). The best association was between the coach and the dietitians (R2: 0.99; p
      < 0.001), and the worst association was between the coach and the medical
      trainees (R2: 0.92; p < 0.001). In the Bland-Altman comparison, the highest error
      rate found between coach and trainees was 5.12% (95% confidence interval [CI]
      3.64-12.37), and the lowest was 1.01% (95%CI 0.72 - 2.58); the highest bias of
      the values described was -0.12 +/- 0.19, and the lowest was -0.01 +/- 0.04.
      CONCLUSION: The data analyzed showed a good correlation between the measurements
      made by the coach and trainees, indicating that ultrasound of the quadriceps
      muscle is a viable and easily applicable tool.

PMID- 29340538
TI  - Autonomic nervous system monitoring in intensive care as a prognostic tool.
      Systematic review.
AB  - OBJECTIVE: To present a systematic review of the use of autonomic nervous system
      monitoring as a prognostic tool in intensive care units by assessing heart rate
      variability. METHODS: Literature review of studies published until July 2016
      listed in PubMed/Medline and conducted in intensive care units, on autonomic
      nervous system monitoring, via analysis of heart rate variability as a prognostic
      tool (mortality study). The following English terms were entered in the search
      field: ("autonomic nervous system" OR "heart rate variability") AND ("intensive
      care" OR "critical care" OR "emergency care" OR "ICU") AND ("prognosis" OR
      "prognoses" OR "mortality"). RESULTS: There was an increased likelihood of death
      in patients who had a decrease in heart rate variability as analyzed via heart
      rate variance, cardiac uncoupling, heart rate volatility, integer heart rate
      variability, standard deviation of NN intervals, root mean square of successive
      differences, total power, low frequency, very low frequency, low frequency/high
      frequency ratio, ratio of short-term to long-term fractal exponents, Shannon
      entropy, multiscale entropy and approximate entropy. CONCLUSION: In patients
      admitted to intensive care units, regardless of the pathology, heart rate
      variability varies inversely with clinical severity and prognosis.

PMID- 29340539
TI  - The spectrum of cardiovascular effects of dobutamine - from healthy subjects to
      septic shock patients.
AB  - Dobutamine is the inotrope most commonly used in septic shock patients to
      increase cardiac output and correct hypoperfusion. Although some experimental and
      clinical studies have shown that dobutamine can improve systemic and regional
      hemodynamics, other research has found that its effects are heterogenous and
      unpredictable. In this review, we analyze the pharmacodynamic properties of
      dobutamine and its physiologic effects. Our goal is to show that the effects of
      dobutamine might differ between healthy subjects, in experimental and clinical
      cardiac failure, in animal models and in patients with septic shock. We discuss
      evidence supporting the claim that dobutamine, in septic shock, frequently
      behaves as a chronotropic and vasodilatory drug, without evidence of inotropic
      action. Since the side effects are very common, and the therapeutic benefits are
      unclear, we suggest that dobutamine should be used cautiously in septic shock.
      Before a definitive therapeutic decision, the efficacy and tolerance of
      dobutamine should be assessed during a brief time with close monitoring of its
      positive and negative side effects.

PMID- 29340540
TI  - Toxic epidermal necrolysis: a paradigm of critical illness.
AB  - Toxic epidermal necrolysis is an adverse immunological skin reaction secondary in
      most cases to the administration of a drug. Toxic epidermal necrolysis, Stevens
      Johnson syndrome, and multiform exudative erythema are part of the same disease
      spectrum. The mortality rate from toxic epidermal necrolysis is approximately
      30%. The pathophysiology of toxic epidermal necrolysis is similar in many
      respects to that of superficial skin burns. Mucosal involvement of the ocular and
      genital epithelium is associated with serious sequelae if the condition is not
      treated early. It is generally accepted that patients with toxic epidermal
      necrolysis are better treated in burn units, which are experienced in the
      management of patients with extensive skin loss. Treatment includes support,
      elimination, and coverage with biosynthetic derivatives of the skin in affected
      areas, treatment of mucosal involvement, and specific immunosuppressive
      treatment. Of the treatments tested, only immunoglobulin G and cyclosporin A are
      currently used in most centers, even though there is no solid evidence to
      recommend any specific treatment. The particular aspects of the treatment of this
      disease include the prevention of sequelae related to the formation of synechiae,
      eye care to prevent serious sequelae that can lead to blindness, and specific
      immunosuppressive treatment. Better knowledge of the management principles of
      toxic epidermal necrolysis will lead to better disease management, higher
      survival rates, and lower prevalence of sequelae.

PMID- 29340542
TI  - Sepsis definitions.

PMID- 29340541
TI  - Safety criteria to start early mobilization in intensive care units. Systematic
      review.
AB  - Mobilization of critically ill patients admitted to intensive care units should
      be performed based on safety criteria. The aim of the present review was to
      establish which safety criteria are most often used to start early mobilization
      for patients under mechanical ventilation admitted to intensive care units.
      Articles were searched in the PubMed, PEDro, LILACS, Cochrane and CINAHL
      databases; randomized and quasi-randomized clinical trials, cohort studies,
      comparative studies with or without simultaneous controls, case series with 10 or
      more consecutive cases and descriptive studies were included. The same was
      performed regarding prospective, retrospective or cross-sectional studies where
      safety criteria to start early mobilization should be described in the Methods
      section. Two reviewers independently selected potentially eligible studies
      according to the established inclusion criteria, extracted data and assessed the
      studies' methodological quality. Narrative description was employed in data
      analysis to summarize the characteristics and results of the included studies;
      safety criteria were categorized as follows: cardiovascular, respiratory,
      neurological, orthopedic and other. A total of 37 articles were considered
      eligible. Cardiovascular safety criteria exhibited the largest number of
      variables. However, respiratory safety criteria exhibited higher concordance
      among studies. There was greater divergence among the authors regarding
      neurological criteria. There is a need to reinforce the recognition of the safety
      criteria used to start early mobilization for critically ill patients; the
      parameters and variables found might contribute to inclusion into service
      routines so as to start, make progress and guide clinical practice.

PMID- 29340543
TI  - COLOSTOMY CLOSURE: RISK FACTORS FOR COMPLICATIONS.
AB  - BACKGROUND: : The restoration of intestinal continuity is an elective procedure
      that is not free of complications; on the contrary, many studies have proven a
      high level of morbidity and mortality. It is multifactorial, and has factors
      inherent to the patients and to the surgical technique. AIM: : To identify
      epidemiological features of patients that underwent ostomy closure analyzing the
      information about the surgical procedure and its arising complications. METHOD: :
      It was realized a retrospective analysis of medical records of patients who
      underwent ostomy closure over a period of seven years (2009-2015). RESULTS: : A
      total of 39 patients were included, 53.8% male and 46.2% female, with mean age of
      52.4 years. Hartmann's procedure and ileostomy were the mainly reasons for
      restoration of intestinal continuity, representing together 87%. Termino-terminal
      anastomosis was performed in 71.8% of cases, by using mainly the manual
      technique. 25.6% developed complications, highlighting anastomotic leakage; there
      were three deaths (7.6%). The surgical time, the necessity of ICU and blood
      transfusion significantly related to post-operative complications. CONCLUSION: :
      It was found that the majority of the patients were male, with an average age of
      52 years. It was observed that the surgical time, the necessity of blood
      transfusion and ICU were factors significantly associated with complications.

PMID- 29340544
TI  - INTERESFINCTERIAL LIGATION OF FISTULA TRACT (LIFT) FOR PATIENTS WITH ANAL
      FISTULAS: A BRAZILIAN BI-INSTITUTIONAL EXPERIENCE.
AB  - BACKGROUND : The best treatment for anal fistula should extirpate infection and
      promote healing of the tract, whilst preserving the anal sphincter complex and
      full continence. AIM: To analyze the success rate after a modified technique for
      ligation of the intersphincteric fistula tract (LIFT) for patients with anal
      fistulas. METHODS: A prospective (observational cohort study) Brazilian bi
      institutional experience with a modified (ligation of the intersphincteric
      fistula tract without excision) LIFT technique was undertaken. A clinical
      database was settled for the following variables: age, gender, BMI,
      comorbidities, distance between external orifice and the anus, previous fistula
      surgery, type of fistula, operative time, intra- and postoperative complications,
      duration of follow-up, and success rate. RESULTS: Between November 2015 and
      January 2017, 38 patients with transsphincteric fistulas were operated on using
      the modified LIFT procedure. Seventeen (44.7%) were men. Median age was 41 (18
      67) years. Median BMI was 26.4 (22-38) kg/m2. Five (13.2%) had undergone previous
      surgery. The fistula was transsphincteric in all cases. Median follow-up was 32
      (range, 14-56) weeks. Success was observed in 30 (79%) patients. CONCLUSIONS: The
      LIFT technique without excision of the fistula tract proved to be safe and
      effective for transsphincteric anal fistulas.

PMID- 29340545
TI  - EFFECTS OF COLD ISCHEMIA TIME ON HEPATIC ALLOGRAFT FUNCTION.
AB  - BACKGROUND
						
						: Cold ischemia time is related to success
      of liver transplantation. 
						
							AIM
						
						: To compare the impact
      of cold ischemia time on allografts locally collected to those collected
      distantly. 
						
							METHODS
						
						: Were evaluated 83
      transplantations. The patients were divided in two groups: those who received
      liver grafts collected from cities out of Curitiba (n=42) and locally (n=41).
      From the donors were compared: cause of death, days at ICU, cardiac arrest,
      vasoactive drugs, lab exams, gender, age, and BMI. Were compared the subsequent
      information of receptors: cold ischemia time, warm ischemia time, length of
      surgery, lab exams, etiology of cirrhosis, MELD score, age, gender, histology of
      graft, use of vasoactive drugs, and blood components transfusion. Were evaluated
      the correlation between cold ischemia time and lab results.
      RESULTS
						
						: The liver grafts collected from other
      cities were submitted to a longer cold ischemia time (500+/-145 min) compared to
      those locally collected (317,85+/-105 min). Donors from other cities showed a
      higher serum sodium level at donation (154+/-16 mEq/dl) compared to those from
      Curitiba (144+/-10 mEq/dl). The length of cold ischemia time was related to serum
      levels of ALT and total bilirubin. 
						
							CONCLUSION
						
						: Liver
      grafts distantly collected underwent longer cold ischemia times, although it
      caused neither histologic injuries nor higher transfusion demands. There is a
      correlation between cold ischemia time and hepatic injury, translated by
      elevation of serum ALT and total bilirubin levels.

PMID- 29340546
TI  - PRE AND POSTOPERATIVE PH MONITORING AND WEIGHT LOSS ANALYSIS IN PATIENTS
      UNDERGOING GASTRIC PLICATION IN ASSOCIATION WITH FUNDOPLICATION.
AB  - BACKGROUND : Obese patients with gastroesophageal reflux disease with
      pathological pH monitoring result may benefit from surgical treatment which is
      based on the fundoplication technique in association with laparoscopic gastric
      plication. The Nissen surgery is the gold standard for surgical treatment of
      gastroesophageal reflux disease, whereas laparoscopic gastric plication is a
      restrictive surgery that consists of the invagination of the greater curvature,
      resulting in weight loss. AIM: To compare pre and postoperative pHmetry results
      and to evaluate weight loss in patients submitted to gastroplasty with
      fundoplication. METHOD: Sixteen patients with class I body mass index with
      symptoms of gastroesophageal reflux with changes of stomach pH and/or erosive
      esophagitis seen in endoscopy were selected The evaluation of the weight and 24-h
      pH monitoring was performed preoperatively and postoperatively. The weight, body
      mass index, percentage of excess weight loss and DeMeester score of patients that
      underwent the surgery were evaluated pre and postoperatively. RESULTS: Regarding
      pH monitoring, the average preoperative DeMeester index was 28.7, which was
      followed by a significant postoperative average reduction to 2.8 (p<0,001).
      Regarding the weight reduction, the average of weight loss was 13.6 kg and body
      mass index of 5.3 kg/m2 (p<0.001). Furthermore, the average percentage of excess
      weight loss was 53.9% (standard deviation=26.2). CONCLUSION: The combination of
      Nissen surgery and gastric plication is a viable procedure and appears to be an
      acceptable option for the treatment of gastroesophageal reflux disease in obese
      patients, especially patients with obesity class I.

PMID- 29340547
TI  - QUALITY OF LIFE AFTER VERTICAL GASTRECTOMY EVALUATED BY THE BAROS QUESTIONNAIRE.
AB  - BACKGROUND
						
						: The satisfactory outcome in the surgical
      treatment of obesity must include, in addition to weight loss, a significant
      change in the pre-existing comorbidities and in the quality of life of the
      patients. 
						
							AIM
						
						: To evaluate the quality of life in
      the late postoperative period in patients that underwent videolaparoscopic sleeve
      gastrectomy. 
						
							METHODS
						
						: Was applied the questionnaire
      "Bariatric Analysis and Reporting Outcome System" (BAROS) in patients that
      underwent videolaparoscopic sleeve gastrectomy.
      RESULTS
						
						: A total of 47 patients between 21-60 years
      old were evaluated. The total mean of the BMI before surgery was 43.06+/-5.87
      kg/m2. The average percentage of the reduction of excess weight after surgery was
      85.46+/-23.6%. The score obtained by patients in the questionnaire about the
      improvement in the quality of life showed excellent (36.17%), very good (40.43%),
      good (21.28%) and reasonable (2.13%) results. There was clinical improvement
      after surgery in all comorbidities investigated.
      CONCLUSION
						
						: BAROS showed excellent results in
      36.17%, very good in 40.43%, good in 21.28% and reasonable in 2.13%. The weight
      loss was critical to improve the quality of life and offered the resolution or
      clinical improvement in all of the investigated comorbidities.

PMID- 29340548
TI  - THE RELATION AMONG THE PHYSICAL ACTIVITY LEVEL DURING LEISURE TIME,
      ANTHROPOMETRY, BODY COMPOSITION, AND PHYSICAL FITNESS OF WOMEN UNDERWENT OF
      BARIATRIC SURGERY AND AN EQUIVALENT GROUP WITH NO SURGERY.
AB  - BACKGROUND: Bariatric surgery is an alternative to the obesity treatment. AIM:
      To compare anthropometric variables such as body composition and physical fitness
      of those who performed Roux-en-Y gastric bypass. METHODS: Were evaluated 108
      women. They were subdivided in three groups: those who performed the bariatric
      surgery by private health insurance (SAS, n=36); by the public health care (SUS,
      n=36), and an equivalent group which did not perform the surgery (NO, n=36). Were
      performed physical fitness, anthropometric and body composition tests. Was
      evaluated the level of physical activity during the leisure period. RESULTS:
      Statistically significant differences were observed between the groups sedentary
      operated (n=28) and sedentary non-operated (n=13) on anthropometry and fat
      percentage, being the highest indexes in the group operated. CONCLUSION: The
      level of physical activity showed a positive influence related to anthropometric
      variables, body composition of the individuals who performed the bariatric
      surgery when compared to the ones non-operated.

PMID- 29340549
TI  - TEACHING MODEL FOR EVALUATION OF THE ABILITY AND COMPETENCE PROGRESS IN
      ENDOSUTURE IN SURGICAL SKILL LABORATORY.
AB  - BACKGROUND : Laparoscopic manual suturing is probably the most difficult skill
      to be acquired in minimally invasive surgery. However, laparoscopic exercise endo
      sutures can be learned with a simulator and are of great practical importance and
      clinical applicability, absorbing concepts that are immediately transferred to
      the operating room. AIM : To assess the progression of skills competence in endo
      sutures through realistic simulation model of systematized education. METHOD :
      Evaluation of the progression of competence of students in three sequential
      stages of training in realistic simulation, pre-test (V.1), teaching concepts
      (V.2) and training station for absorption of video concepts in surgery -
      ergonomics, stereotaxia, ambidexterity, haptic touch, fucral effect, applied in
      the manufacture of points corresponding to a Nissen fundoplication, in endo
      suture for realistic simulation. RESULTS : All students who attended the course
      absorbed the video concepts in surgery; most participants showed steady and
      continued improvement and during the stages of training, obtained progression of
      appropriate skills, defining competence and validation of the teaching model to
      achieve proficiency. CONCLUSIONS : The teaching model was adequate, safe,
      revealed the profile of the student, the evolutionary powers of the endo-sutures
      performance and critical analysis of the training to achieve proficiency in
      bariatric procedures.

PMID- 29340550
TI  - MODIFIED HEIDELBERG TECHNIQUE FOR PANCREATIC ANASTOMOSIS.
AB  - BACKGROUND
						
						: Pancreatic fistula is a major cause of
      morbidity and mortality after pancreatoduodenectomy. To prevent this
      complication, many technical procedures have been described. 
						AIM: To
      present a novel technique based on slight modifications of the original
      Heidelberg technique, as new pancreatojejunostomy technique for reconstruction of
      pancreatic stump after pancreatoduodenectomy and present initial results.
      METHOD: The technique was used for patients with soft or hard pancreas and
      with duct size smaller or larger than 3 mm. The stitches are performed with 5-0
      double needle prolene at the 2 o'clock, 4 o'clock, 6 o'clock, 8 o'clock, 10
      o'clock, and 12 o'clock, positions, full thickness of the parenchyma. A running
      suture is performed with 4-0 single needle prolene on the posterior and anterior
      aspect the pancreatic parenchyma with the jejunal seromuscular layer. A plastic
      stent, 20 cm long, is inserted into the pancreatic duct and extended into the
      jejunal lumen. Two previously placed hemostatic sutures on the superior and
      inferior edges of the remnant pancreatic stump are passed in the jejunal
      seromuscular layer and tied. 
						
							RESULTS
						
						: Seventeen
      patients underwent pancreatojejunostomy after pancreatoduodenectomy for different
      causes. None developed grade B or C pancreatic fistula. Biochemical leak
      according to the new definition (International Study Group on Pancreatic Surgery)
      was observed in four patients (23.5%). No mortality was observed.
      CONCLUSION
						
						: Early results of this technique confirm
      that it is simple, reliable, easy to perform, and easy to learn. This technique
      is useful to reduce the incidence of pancreatic fistula after
      pancreatoduodenectomy.

PMID- 29340551
TI  - MINI-GASTRIC BYPASS: DESCRIPTION OF THE TECHNIQUE AND PRELIMINARY RESULTS.
AB  - BACKGROUND : In recent years, a surgical technique known as single-anastomosis
      gastric bypass or mini-gastric bypass has been developed. Its frequency of
      performance has increased considerably in the current decade. AIM : To describe
      the mini-gastric bypass technique, its implementation and preliminary results in
      a university hospital. METHODS : This is an ongoing prospective trial to evaluate
      the long-term effects of mini-gastric bypass. The main features of the operation
      were: a gastric pouch with about 15-18 cm (50-150 ml) with a gastroenteric
      anastomosis in the pre-colic isoperistaltic loop 200 cm from the duodenojejunal
      angle (biliopancreatic loop). RESULTS : Seventeen individuals have undergone
      surgery. No procedure needed to be converted to open approach. The overall 30-day
      morbidity was 5.9% (one individual had intestinal obstruction caused by
      adhesions). There was no mortality. CONCLUSION : Mini-gastric bypass is a
      feasible and safe bariatric surgical procedure.

PMID- 29340552
TI  - SINGLE ANASTOMOSIS GASTRIC BYPASS (ONE ANASTOMOSIS GASTRIC BYPASS OR MINI GASTRIC
      BYPASS): THE EXPERIENCE WITH BILLROTH II MUST BE CONSIDERED AND IS A CHALLENGE
      FOR THE NEXT YEARS.
AB  - INTRODUCTION: Single anastomosis gastric bypass (one anastomosis gastric bypass
      or mini-gastric bypass) has been presented as an option of surgical treatment for
      obese patients in order to reduce operation time and avoiding eventual
      postoperative complications after Roux-en-Y gastric bypass.The main late
      complication could be related to bile reflux. AIM: To report the experiences
      published after Billroth II anastomosis and its adverse effects regarding
      symptoms and damage on the gastric and esophageal mucosa . METHOD: For data
      recollection Medline, Pubmed, Scielo and Cochrane database were accessed, giving
      a total of 168 papers being chosen 57 of them. RESULTS: According the reported
      results during open era surgery for peptic disease and more recent results for
      gastric cancer surgery, bile reflux and its consequences are more frequent after
      Billroth II operation compared to Roux-en-Y gastrojejunal anastomosis.
      CONCLUSION: These findings must be considered for the indication of bariatric
      surgery.

PMID- 29340553
TI  - HEPATOCELLULAR CARCINOMA: DIAGNOSIS AND OPERATIVE MANAGEMENT.
AB  - INTRODUCTION: Hepatocellular carcinoma is an aggressive malignant tumor with high
      lethality. AIM: To review diagnosis and management of hepatocellular carcinoma.
      METHODS: Literature review using web databases Medline/PubMed. RESULTS:
      Hepatocellular carcinoma is a common complication of hepatic cirrhosis. Chronic
      viral hepatitis B and C also constitute as risk factors for its development. In
      patients with cirrhosis, hepatocelular carcinoma usually rises upon malignant
      transformation of a dysplastic regenerative nodule. Differential diagnosis with
      other liver tumors is obtained through computed tomography scan with intravenous
      contrast. Magnetic resonance may be helpful in some instances. The only
      potentially curative treatment for hepatocellular carcinoma is tumor resection,
      which may be performed through partial liver resection or liver transplantation.
      Only 15% of all hepatocellular carcinomas are amenable to operative treatment.
      Patients with Child C liver cirrhosis are not amenable to partial liver
      resections. The only curative treatment for hepatocellular carcinomas in patients
      with Child C cirrhosis is liver transplantation. In most countries, only patients
      with hepatocellular carcinoma under Milan Criteria are considered candidates to a
      liver transplant. CONCLUSION: Hepatocellular carcinoma is potentially curable if
      discovered in its initial stages. Medical staff should be familiar with
      strategies for early diagnosis and treatment of hepatocellular carcinoma as a way
      to decrease mortality associated with this malignant neoplasm.

PMID- 29340554
TI  - FUNDOPLICATION CONVERSION IN ROUX-EN-Y GASTRIC BYPASS FOR CONTROL OF OBESITY AND
      GASTROESOPHAGEAL REFLUX: SYSTEMATIC REVIEW.
AB  - INTRODUCTION    : Obesity is related with higher incidence of gastroesophageal
      reflux disease. Antireflux surgery has inadequate results when associated with
      obesity, due to migration and/or subsequent disruption of antireflux wrap.
      Gastric bypass, meanwhile, provides good control of gastroesophageal reflux.
      OBJECTIVE: To evaluate the technical difficulty in performing gastric bypass in
      patients previously submitted to antireflux surgery, and its effectiveness in
      controlling gastroesophageal reflux. METHODS: Literature review was conducted
      between July to October 2016 in Medline database, using the following search
      strategy: ("Gastric bypass" OR "Roux-en-Y") AND ("Fundoplication" OR "Nissen ')
      AND ("Reoperation" OR "Reoperative" OR "Revisional" OR "Revision" OR
      "Complications"). RESULTS: Were initially classified 102 articles; from them at
      the end only six were selected by exclusion criteria. A total of 121 patients
      were included, 68 women. The mean preoperative body mass index was 37.17 kg/m2
      and age of 52.60 years. Laparoscopic Nissen fundoplication was the main prior
      antireflux surgery (70.58%). The most common findings on
      esophagogastroduodenoscopy were esophagitis (n=7) and Barrett's esophagus (n=6);
      the most common early complication was gastric perforation (n=7), and most common
      late complication was stricture of gastrojejunostomy (n=9). Laparoscopic gastric
      bypass was performed in 99 patients, with an average time of 331 min. Most
      patients had complete remission of symptoms and efficient excess weight loss.
      CONCLUSION: Although technically more difficult, with higher incidence of
      complications, gastric bypass is a safe and effective option for controlling
      gastroesophageal reflux in obese patients previously submitted to antireflux
      surgery, with the added benefit of excess weight loss.

PMID- 29340556
TI  - AMYAND'S HERNIA: OUR EPERIENCE AND REVIEW OF LITERATURE.

PMID- 29340555
TI  - THE ROLE OF THE SLEEVE GASTRECTOMY AND THE MANAGEMENT OF TYPE 2 DIABETES.
AB  - BACKGROUND : Currently, bariatric surgery has promoted weight loss and improved
      glycemic control in obese patients through different techniques, including
      vertical sleeve gastrectomy. AIM : Present and update the different vertical
      sleeve gastrectomy ways of action, both in the treatment of obesity and diabetes,
      approaching its potential effect on gastrointestinal physiology, as well as the
      benefits achieved by this manipulation. METHODS : Pubmed database search was used
      crossing the headings: obesity, type 2 diabetes and sleeve gastrectomy. RESULTS :
      Published data have shown that short-term weight loss tends to be higher in
      patients undergoing vertical sleeve gastrectomy compared to Roux-en-Y gastric
      bypass. In relation to glycemic control, the procedure demonstrated remission of
      diabetes in up to 60% after one year of surgery. After three years, however,
      differences in remission rate between surgical and clinical group was not
      observed, questioning the durability of the technical in a long-term. CONCLUSION
      : Despite showing good results, both in the weight loss and co-morbidities,
      conflicting results reinforce the need for more studies to prove the efficiency
      of the vertical sleeve gastrectomy as well as to understand its action about the
      molecular mechanisms involved in the disease.

PMID- 29340557
TI  - AN UNUSUAL CAUSE OF ACUTE ABDOMEN: SPLENIC INFARCTION.

PMID- 29340558
TI  - LAPAROSCOPIC ABDOMINOPERINEAL RESECTION WITH SACRECTOMY: TECHNICAL DETAILS AND
      PITFALLS.

PMID- 29340559
TI  - Serial Magnetic Resonance Imaging Changes in a Patient With Late-Onset Cobalamin
      C Disease With a Misdiagnosis of Metachromatic Leukodystrophy.

PMID- 29340560
TI  - Physician-Scientist Career Awards and a Dilemma: National Institute of Child
      Health and Human Development K Awards-Individual, Institutional, or National?

PMID- 29340561
TI  - Generic Substitution Rates of Oral Contraceptives and Associated Out-of-Pocket
      Cost Savings Between January 2010 and December 2014.

PMID- 29340563
TI  - Citation Errors in Figure 2.

PMID- 29340562
TI  - Medicare Spending and Potential Savings on Brand-Name Drugs With Available
      Generic Substitutes Excluded by 2 Large Pharmacy Benefit Managers, 2012 Through
      2015.

PMID- 29340565
TI  - Using Chaplains to Facilitate Advance Care Planning in Medical Practice.

PMID- 29340564
TI  - Changes in Health Care Use Associated With the Introduction of Hospital Global
      Budgets in Maryland.
AB  - Importance: In 2014, the State of Maryland placed the majority of its hospitals
      under all-payer global budgets for inpatient, hospital outpatient, and emergency
      department care. Goals of the program included reducing unnecessary hospital
      utilization and encouraging greater use of primary care. Objective: To compare
      changes in hospital and primary care use through the first 2 years of Maryland's
      hospital global budget program among fee-for-service Medicare beneficiaries in
      Maryland vs matched control areas. Design, Setting, and Participants: We matched
      8 Maryland counties (94 967 beneficiaries) with hospitals in the program to 27
      non-Maryland control counties (206 389 beneficiaries). Using difference-in
      differences analysis, we compared changes in hospital and primary care use in
      Maryland vs the control counties from before (2009-2013) to after (2014-2015) the
      payment change, using 2 different assumptions. First, we assumed that
      preintervention differences between Maryland and the control counties would have
      remained constant past 2014 had Maryland not implemented global budgets (parallel
      trend assumption). Second, we assumed that differences in preintervention trends
      would have continued without the payment change (differential trend assumption).
      Main Outcomes and Measures: Hospital stays (defined as admissions and observation
      stays); return hospital stays within 30 days of a prior hospital stay; emergency
      department visits that did not result in admission; price-standardized hospital
      outpatient department (HOPD) utilization; and visits with primary care physicians
      (overall and within 7 days of a hospital stay). Results: We matched 8 Maryland
      counties with hospitals in the program (94 967 beneficiaries; 41.8% male; mean
      [SD] age, 72.3 [12.2] years) to 27 non-Maryland control counties (206 389
      beneficiaries; 42.8% male; mean [SD] age, 71.7 [12.5] years). Assuming parallel
      trends, we estimated a differential change in Maryland of -0.47 annual hospital
      stays per 100 beneficiaries (95% CI, -1.65 to 0.72; P = .43) from the
      preintervention period (2009-2013) to 2015, but assuming differential trends, we
      estimated a differential change in Maryland of -1.24 stays per 100 beneficiaries
      (95% CI, -2.46 to -0.02; P = .047). Assuming parallel trends, we found a
      significant increase in primary care visits (+10.6 annual visits/100
      beneficiaries; 95% CI, 4.6 to 16.6 annual visits/100 beneficiaries; P = .001),
      but assuming differential trends, we found no change (-0.8 visits/100
      beneficiaries; 95% CI, -10.6 to 9.0 visits/100 beneficiaries; P = .87). Comparing
      estimates with both trend assumptions, we found no consistent changes in
      emergency department visits, return hospital stays, HOPD use, or
      posthospitalization primary care visits associated with Maryland's program.
      Conclusions and Relevance: We did not find consistent evidence that Maryland's
      hospital global budget program was associated with reductions in hospital use or
      increases in primary care visits among fee-for-service Medicare beneficiaries
      after 2 years. Evaluations over longer periods should be pursued.

PMID- 29340566
TI  - Annals for Educators - 16 January 2018.

PMID- 29340567
TI  - Annals for Hospitalists - 16 January 2018.

PMID- 29340568
TI  - Maryland's All-Payer Health Reform-A Promising Work in Progress.

PMID- 29340570
TI  - Name and Characteristics of National Institutes of Health R01-Funded Pediatric
      Physician-Scientists: Hope and Challenges for the Vanishing Pediatric Physician
      Scientists.

PMID- 29340569
TI  - Associations of the Top 20 Alzheimer Disease Risk Variants With Brain
      Amyloidosis.
AB  - Importance: Late-onset Alzheimer disease (AD) is highly heritable. Genome-wide
      association studies have identified more than 20 AD risk genes. The precise
      mechanism through which many of these genes are associated with AD remains
      unknown. Objective: To investigate the association of the top 20 AD risk variants
      with brain amyloidosis. Design, Setting, and Participants: This study analyzed
      the genetic and florbetapir F 18 data from 322 cognitively normal control
      individuals, 496 individuals with mild cognitive impairment, and 159 individuals
      with AD dementia who had genome-wide association studies and 18F-florbetapir
      positron emission tomographic data from the Alzheimer's Disease Neuroimaging
      Initiative (ADNI), a prospective, observational, multisite tertiary center
      clinical and biomarker study. This ongoing study began in 2005. Main Outcomes and
      Measures: The study tested the association of AD risk allele carrier status
      (exposure) with florbetapir mean standard uptake value ratio (outcome) using
      stepwise multivariable linear regression while controlling for age, sex, and
      apolipoprotein E epsilon4 genotype. The study also reports on an exploratory 3
      dimensional stepwise regression model using an unbiased voxelwise approach in
      Statistical Parametric Mapping 8 with cluster and significance thresholds at 50
      voxels and uncorrected P < .01. Results: This study included 977 participants
      (mean [SD] age, 74 [7.5] years; 535 [54.8%] male and 442 [45.2%] female) from the
      ADNI-1, ADNI-2, and ADNI-Grand Opportunity. The adenosine triphosphate-binding
      cassette subfamily A member 7 (ABCA7) gene had the strongest association with
      amyloid deposition (chi2 = 8.38, false discovery rate-corrected P < .001), after
      apolioprotein E epsilon4. Significant associations were found between ABCA7 in
      the asymptomatic and early symptomatic disease stages, suggesting an association
      with rapid amyloid accumulation. The fermitin family homolog 2 (FERMT2) gene had
      a stage-dependent association with brain amyloidosis (FERMT2 * diagnosis chi2 =
      3.53, false discovery rate-corrected P = .05), which was most pronounced in the
      mild cognitive impairment stage. Conclusions and Relevance: This study found an
      association of several AD risk variants with brain amyloidosis. The data also
      suggest that AD genes might differentially regulate AD pathologic findings across
      the disease stages.

PMID- 29340572
TI  - Overuse of Percutaneous Coronary Interventions.

PMID- 29340571
TI  - Comparison of Physician Visual Assessment With Quantitative Coronary Angiography
      in Assessment of Stenosis Severity in China.
AB  - Importance: Although physician visual assessment (PVA) of stenosis severity is a
      standard clinical practice to support decisions for coronary revascularization,
      there are concerns about its accuracy. Objective: To compare PVA with
      quantitative coronary angiography (QCA) as a means of assessing stenosis severity
      among patients undergoing percutaneous coronary intervention (PCI) in China.
      Design, Setting, and Participants: A cross-sectional study (2012-2013) of a
      random subset of 1295 patients from the China Patient-centered Evaluative
      Assessment of Cardiac Events (PEACE) Prospective PCI Study was carried out. The
      PEACE Prospective PCI study recruited a consecutive sample of patients undergoing
      PCI at 35 hospitals in 18 provinces of China. The coronary angiograms of this
      subset of participants were reviewed using QCA by 2 independent core laboratories
      blinded to PVA readings. Main Outcomes and Measures: Differences between PVA and
      QCA assessments of stenosis severity for lesions for which PCI was performed and
      variation of these differences among hospitals and physicians, stratified by the
      diagnosis of acute myocardial infarction (AMI). Results: In patients without AMI,
      the mean (SD) age was 62 (10) years, and 217 (31.5%) were women; in patients with
      AMI, the mean (SD) age was 60 (11) years, and 153 (25.2%) were women. The mean
      (SD) percent diameter stenosis by PVA was 16.0% (11.5%) greater than that by QCA
      in patients without AMI and 10.2% (12.3%) in those with AMI (P < .001 for both
      comparisons). In patients without AMI, of 837 lesions with 70% or more stenosis
      by PVA, 427 (50.6%) were less than 70% by QCA; in patients with AMI, similar
      patterns were observed to a lesser extent. Among patients without AMI, only 4
      (0.47%) lesions were additionally assessed with fractional flow reserve. Among 30
      hospitals, the difference between PVA and QCA readings of stenosis severity
      varied from 7.6% (95% CI, 0.4%-14.7%) to 21.3% (95% CI, 17.1%-24.9%) among non
      AMI patients. Across 57 physicians, this difference varied from 6.9% (95% CI, 
      1.4%-15.3%) to 26.4% (95% CI, 21.5%-31.4%). Conclusions and Relevance: For
      coronary lesions treated with PCI in China, PVA reported substantially higher
      readings of stenosis severity than QCA, with large variation across hospitals and
      physicians. These findings highlight the need to improve the accuracy of
      information used to guide treatment decisions in catheterization laboratories.

PMID- 29340573
TI  - Challenges for Today's Pediatric Physician-Scientists.

PMID- 29340575
TI  - The Fragile State of the National Institutes of Health Pediatric Research
      Portfolio, 1992-2015: Doing More With Less?
AB  - In this article, we examine the status of the National Institutes of Health (NIH)
      pediatric research portfolio between start of federal fiscal year (FY) 1992 and
      end of FY 2015. The NIH experienced the greatest mean annual growth rate during
      the "doubling era" (FY 1998-2003): both the NIH budget (13.5%) and pediatric
      research portfolios (11.5%) increased annually by double digits. However, in the
      "postdoubling" era (FY 2004-2009), both the NIH (2.0%) and pediatric (-0.2%) mean
      annual growth rates decreased dramatically. In the most recent era (FY 2010
      2015), the NIH mean annual growth rate has been flat (-0.1%) and pediatric
      research funding has posted very modest gains (3.5%) without accounting for 1
      time increases under the 2009 American Recovery and Reinvestment Act. We offer
      recommendations to protect against further erosion of the pediatric research
      portfolio because continuation of these trends will have a negative effect on the
      health of children during their childhood and as adults. As capacity to conduct
      basic and applied research is further constrained, it will be a challenge for
      pediatric researchers to do more with less and less.

PMID- 29340574
TI  - Effect of General Anesthesia and Conscious Sedation During Endovascular Therapy
      on Infarct Growth and Clinical Outcomes in Acute Ischemic Stroke: A Randomized
      Clinical Trial.
AB  - Importance: Endovascular therapy (EVT) is the standard of care for select
      patients who had a stroke caused by a large vessel occlusion in the anterior
      circulation, but there is uncertainty regarding the optimal anesthetic approach
      during EVT. Observational studies suggest that general anesthesia (GA) is
      associated with worse outcomes compared with conscious sedation (CS). Objective:
      To examine the effect of type of anesthesia during EVT on infarct growth and
      clinical outcome. Design, Setting, and Participants: The General or Local
      Anesthesia in Intra Arterial Therapy (GOLIATH) trial was a single-center
      prospective, randomized, open-label, blinded end-point evaluation that enrolled
      patients from March 12, 2015, to February 2, 2017. Although the trial screened
      1501 patients, it included 128 consecutive patients with acute ischemic stroke
      caused by large vessel occlusions in the anterior circulation within 6 hours of
      onset; 1372 patients who did not fulfill inclusion criteria and 1 who did not
      provide consent were excluded. Primary analysis was unadjusted and according to
      the intention-to-treat principle. Interventions: Patients were randomized to
      either the GA group or the CS group (1:1 allocation) before EVT. Main Outcomes
      and Measures: The primary end point was infarct growth between magnetic resonance
      imaging scans performed before EVT and 48 to 72 hours after EVT. The hypothesis
      formulated before data collection was that patients who were under CS would have
      less infarct growth. Results: Of 128 patients included in the trial, 65 were
      randomized to GA, and 63 were randomized to CS. For the entire cohort, the mean
      (SD) age was 71.4 (11.4) years, and 62 (48.4%) were women. Baseline demographic
      and clinical variables were balanced between the GA and CS treatment arms. The
      median National Institutes of Health Stroke Scale score was 18 (interquartile
      range [IQR], 14-21). Four patients (6.3%) in the CS group were converted to the
      GA group. Successful reperfusion was significantly higher in the GA arm than in
      the CS arm (76.9% vs 60.3%; P = .04). The difference in the volume of infarct
      growth among patients treated under GA or CS did not reach statistical
      significance (median [IQR] growth, 8.2 [2.2-38.6] mL vs 19.4 [2.4-79.0] mL; P =
      .10). There were better clinical outcomes in the GA group, with an odds ratio for
      a shift to a lower modified Rankin Scale score of 1.91 (95% CI, 1.03-3.56).
      Conclusions and Relevance: For patients who underwent thrombectomy for acute
      ischemic stroke caused by large vessel occlusions in the anterior circulation, GA
      did not result in worse tissue or clinical outcomes compared with CS. Trial
      Registration: clinicaltrials.gov Identifier: NCT02317237.

PMID- 29340576
TI  - Association of National Institute of Child Health and Human Development Career
      Development Awards With Subsequent Research Project Grant Funding.
AB  - Importance: Investing in the next generation of researchers is essential, as
      recently highlighted in the 21st Century Cures Act. From its inception, the
      Eunice Kennedy Shriver National Institute of Child Health and Human Development
      (NICHD) has supported training and career development to ensure a robust pipeline
      of investigators who are prepared to lead their respective fields of inquiry. In
      recent years, the NICHD has emphasized institutional over individual training
      awards to a greater degree than many other National Institutes of Health
      institutes of similar size. Objective: To evaluate the success of individuals
      supported by NICHD career development and training awards, as measured by
      subsequent application and receipt of independent National Institutes of Health
      research project grant funding. Design, Setting, and Participants: This
      retrospective cohort study identified 417 physician-scholars who were supported
      by NICHD career development awards between October 1, 1999, and September 30,
      2001. This period was selected to allow adequate follow-up of research project
      grant applications and funding. Among these physician-scholars, 355 met inclusion
      criteria. Main Outcomes and Measures: The primary outcomes were the numbers of
      research project grant applications submitted and, of these, the numbers that
      were successfully funded. Results: Among 355 physician-scientists, scholars who
      had an MD degree only and received a K award or both an individual K award and
      institutional K12 support were more likely than those who received only K12
      support (individual K only vs institutional K12 only: odds ratio [OR], 4.86; 95%
      CI, 1.83-13.62; both K and K12 vs K12 only: OR, 3.19; 95% CI, 1.46-7.10) to apply
      for subsequent project grant funding (88.0% vs 82.8% vs 60.1%, respectively; P <
      .001) and to receive it (60.0% vs 60.9% vs 32.9%, respectively; P < .001). For
      physicians with both MD and PhD degrees, neither application nor funding rates
      were statistically significantly different whether their career development was
      supported by individual or institutional awards. Conclusions and Relevance:
      Physician-scholars are more likely to apply for and receive a National Institutes
      of Health research grant if they are trained on an individual career development
      award, with or without an institutional training award. Based on the data, the
      NICHD intends to provide a greater proportion of its career development fund
      allocation to individual awards. The NICHD recognizes the importance of
      institutional awards and will continue to support them. The NICHD remains
      committed to training and intends to maintain its investment in training and
      career development awards going forward.

PMID- 29340577
TI  - Lactation Duration and Progression to Diabetes in Women Across the Childbearing
      Years: The 30-Year CARDIA Study.
AB  - Importance: Lactation duration has shown weak protective associations with
      incident diabetes (3%-15% lower incidence per year of lactation) in older women
      based solely on self-report of diabetes, studies initiated beyond the
      reproductive period are vulnerable to unmeasured confounding or reverse causation
      from antecedent biochemical risk status, perinatal outcomes, and behaviors across
      the childbearing years. Objective: To evaluate the association between lactation
      and progression to diabetes using biochemical testing both before and after
      pregnancy and accounting for prepregnancy cardiometabolic measures, gestational
      diabetes (GD), and lifestyle behaviors. Design, Setting, and Participants: For
      this US multicenter, community-based 30-year prospective cohort study, there were
      1238 women from the Coronary Artery Risk Development in Young Adults (CARDIA)
      study of young black and white women ages 18 to 30 years without diabetes at
      baseline (1985-1986) who had 1 or more live births after baseline, reported
      lactation duration, and were screened for diabetes up to 7 times during 30 years
      after baseline (1986-2016). Exposures: Time-dependent lactation duration
      categories (none, >0 to 6 months, >6 to <12 months, and >=12 months) across all
      births since baseline through 30 years. Main Outcomes and Measures: Diabetes
      incidence rates per 1000 person-years and adjusted relative hazards (RH) with
      corresponding 95% CIs, as well as proportional hazards regression models adjusted
      for biochemical, sociodemographic, and reproductive risk factors, as well as
      family history of diabetes, lifestyle, and weight change during follow-up.
      Results: Overall 1238 women were included in this analysis (mean [SD] age, 24.2
      [3.7] years; 615 black women). There were 182 incident diabetes cases during 27
      598 person-years for an overall incidence rate of 6.6 cases per 1000 person-years
      (95% CI, 5.6-7.6); and rates for women with GD and without GD were 18.0 (95% CI,
      13.3-22.8) and 5.1 (95% CI, 4.2-6.0), respectively (P for difference < .001).
      Lactation duration showed a strong, graded inverse association with diabetes
      incidence: adjusted RH for more than 0 to 6 months, 0.75 (95% CI, 0.51-1.09);
      more than 6 months to less than 12 months, 0.52 (95% CI, 0.31-0.87), and 12
      months or more 0.53 (0.29-0.98) vs none (0 days) (P for trend = .01). There was
      no evidence of effect modification by race, GD, or parity. Conclusions and
      Relevance: This study provides longitudinal biochemical evidence that lactation
      duration is independently associated with lower incidence of diabetes. Further
      investigation is required to elucidate mechanisms that may explain this
      relationship.

PMID- 29340578
TI  - Clinical recommendations for high altitude exposure of individuals with pre
      existing cardiovascular conditions: A joint statement by the European Society of
      Cardiology, the Council on Hypertension of the European Society of Cardiology,
      the European Society of Hypertension, the International Society of Mountain
      Medicine, the Italian Society of Hypertension and the Italian Society of Mountain
      Medicine.
AB  - Take home figureAdapted from Bartsch and Gibbs2 Physiological response to
      hypoxia. Life-sustaining oxygen delivery, in spite of a reduction in the partial
      pressure of inhaled oxygen between 25% and 60% (respectively at 2500 m and 8000
      m), is ensured by an increase in pulmonary ventilation, an increase in cardiac
      output by increasing heart rate, changes in vascular tone, as well as an increase
      in haemoglobin concentration. BP, blood pressure; HR, heart rate; PaCO2, partial
      pressure of arterial carbon dioxide.

PMID- 29340579
TI  - Extracorporeal life support in thoracic surgery.

PMID- 29340580
TI  - Population Specific Biomarkers of Human Aging: A Big Data Study Using South
      Korean, Canadian, and Eastern European Patient Populations.
AB  - Accurate and physiologically meaningful biomarkers for human aging are key to
      assessing antiaging therapies. Given ethnic differences in health, diet,
      lifestyle, behavior, environmental exposures, and even average rate of biological
      aging, it stands to reason that aging clocks trained on datasets obtained from
      specific ethnic populations are more likely to account for these potential
      confounding factors, resulting in an enhanced capacity to predict chronological
      age and quantify biological age. Here, we present a deep learning-based
      hematological aging clock modeled using the large combined dataset of Canadian,
      South Korean, and Eastern European population blood samples that show increased
      predictive accuracy in individual populations compared to population specific
      hematologic aging clocks. The performance of models was also evaluated on
      publicly available samples of the American population from the National Health
      and Nutrition Examination Survey (NHANES). In addition, we explored the
      association between age predicted by both population specific and combined
      hematological clocks and all-cause mortality. Overall, this study suggests (a)
      the population specificity of aging patterns and (b) hematologic clocks predicts
      all-cause mortality. The proposed models were added to the freely-available
      Aging.AI system expanding the range of tools for analysis of human aging.

PMID- 29340581
TI  - Gene Turnover and Diversification of the alpha- and beta-Globin Gene Families in
      Sauropsid Vertebrates.
AB  - The genes that encode the alpha- and beta-chain subunits of vertebrate hemoglobin
      have served as a model system for elucidating general principles of gene family
      evolution, but little is known about patterns of evolution in amniotes other than
      mammals and birds. Here, we report a comparative genomic analysis of the alpha-
      and beta-globin gene clusters in sauropsids (archosaurs and nonavian reptiles).
      The objectives were to characterize changes in the size and membership
      composition of the alpha- and beta-globin gene families within and among the
      major sauropsid lineages, to reconstruct the evolutionary history of the
      sauropsid alpha- and beta-globin genes, to resolve orthologous relationships, and
      to reconstruct evolutionary changes in the developmental regulation of gene
      expression. Our comparisons revealed contrasting patterns of evolution in the
      unlinked alpha- and beta-globin gene clusters. In the alpha-globin gene cluster,
      which has remained in the ancestral chromosomal location, evolutionary changes in
      gene content are attributable to the differential retention of paralogous gene
      copies that were present in the common ancestor of tetrapods. In the beta-globin
      gene cluster, which was translocated to a new chromosomal location, evolutionary
      changes in gene content are attributable to differential gene gains (via lineage
      specific duplication events) and gene losses (via lineage-specific deletions and
      inactivations). Consequently, all major groups of amniotes possess unique
      repertoires of embryonic and postnatally expressed beta-type globin genes that
      diversified independently in each lineage. These independently derived beta-type
      globins descend from a pair of tandemly linked paralogs in the most recent common
      ancestor of sauropsids.

PMID- 29340582
TI  - Immune-Related Transcriptional Responses to Parasitic Infection in a Naturally
      Inbred Fish: Roles of Genotype and Individual Variation.
AB  - Parasites are strong drivers of evolutionary change and the genetic variation of
      both host and parasite populations can co-evolve as a function of parasite
      virulence and host resistance. The role of transcriptome variation in specific
      interactions between host and parasite genotypes has been less studied and can be
      confounded by differences in genetic variation. We employed two naturally inbred
      lines of a self-fertilizing fish to estimate the role of host genotype in the
      transcriptome response to parasite infection using RNA-seq. In addition, we
      targeted several differentially expressed immune-related genes to further
      investigate the relative role of individual variation in the immune response
      using RT-qPCR, taking advantage of the genomic uniformity of the self-fertilizing
      lines. We found significant differences in gene expression between lines in
      response to infection both in the transcriptome and in individual gene RT-qPCR
      analyses. Individual RT-qPCR analyses of gene expression identified significant
      variance differences between lines for six genes but only for three genes between
      infected and control fish. Our results indicate that although the genetic
      background plays an important role in the transcriptome response to parasites, it
      cannot fully explain individual differences within genetically homogeneous lines,
      which can be important for determining the response to parasites.

PMID- 29340583
TI  - Functional analysis of the Helicobacter pullorum N-linked protein glycosylation
      system.
AB  - N-linked protein glycosylation systems operate in species from all three domains
      of life. The model bacterial N-linked glycosylation system from Campylobacter
      jejuni is encoded by pgl genes present at a single chromosomal locus. This gene
      cluster includes the pglB oligosaccharyltransferase responsible for transfer of
      glycan from lipid carrier to protein. Although all genomes from species of the
      Campylobacter genus contain a pgl locus, among the related Helicobacter genus
      only three evolutionarily related species (H. pullorum, H. canadensis and H.
      winghamensis) potentially encode N-linked protein glycosylation systems.
      Helicobacter putative pgl genes are scattered in five chromosomal loci and
      include two putative oligosaccharyltransferase-encoding pglB genes per genome. We
      have previously demonstrated the in vitro N-linked glycosylation activity of H.
      pullorum resulting in transfer of a pentasaccharide to a peptide at asparagine
      within the sequon (D/E)XNXS/T. In this study, we identified the first H. pullorum
      N-linked glycoprotein, termed HgpA. Production of histidine-tagged HgpA in the
      background of insertional knockout mutants of H. pullorum pgl/wbp genes followed
      by analysis of HgpA glycan structures demonstrated the role of individual gene
      products in the PglB1-dependent N-linked protein glycosylation pathway.
      Glycopeptide purification by zwitterionic-hydrophilic interaction liquid
      chromatography coupled with tandem mass spectrometry identified six glycosites
      from five H. pullorum proteins, which was consistent with proteins reactive with
      a polyclonal antiserum generated against glycosylated HgpA. This study
      demonstrates functioning of a H. pullorum N-linked general protein glycosylation
      system.

PMID- 29340585
TI  - Spinal Tuberculosis: Clinicoradiological Findings in 274 Patients.
AB  - Background: Mycobacterium tuberculosis is a major cause of myelopathy and
      radiculopathy in settings with a high prevalence of tuberculosis/human
      immunodeficiency virus (HIV) coinfection. However, a paucity of publications
      exists on the spectrum of neurological and magnetic resonance (MR) imaging
      findings of spinal tuberculosis in these populations. Methods: We conducted a
      retrospective study of adults with spinal tuberculosis at a referral center in
      South Africa for patients with spinal disease without bony involvement seen at
      plain film radiography. We report the clinical, laboratory and spinal MR imaging
      findings, compare HIV-infected and HIV-uninfected patients, and correlate
      clinical and cerebrospinal fluid findings with those of MR imaging. Results: Of
      274 patients, 209 (76%) were HIV infected and 49 (18%) were HIV uninfected.
      Radiculomyelitis occurred in 77% (n = 210), and spondylitis in 39% (n = 106).
      Subdural abscess (n = 42) and intramedullary tuberculoma (n = 33) were common. In
      24% of HIV-infected and 14% of HIV-uninfected patients, spinal disease manifested
      as a paradoxical tuberculosis reaction, frequently following tuberculous
      meningitis. The triad of neurological deficit, fever, and back pain was similar
      in patients with spondylitis (24%), epi/subdural abscess without bony disease
      (14%), meningoradiculitis (17%), and isolated myelitis (17%) . Conclusions:
      Radiculomyelitis is a common manifestation of spinal tuberculosis in settings
      with high tuberculosis/HIV prevalence, often presenting as a paradoxical
      reaction. We describe a high frequency of rarely reported spinal tuberculosis
      manifestations, suggesting that these are more common than implied by the
      literature.

PMID- 29340586
TI  - Data Sharing.

PMID- 29340584
TI  - Long-interval intracortical inhibition as biomarker for epilepsy: a transcranial
      magnetic stimulation study.
AB  - Cortical excitability, as measured by transcranial magnetic stimulation combined
      with electromyography, is a potential biomarker for the diagnosis and follow-up
      of epilepsy. We report on long-interval intracortical inhibition data measured in
      four different centres in healthy controls (n = 95), subjects with refractory
      genetic generalized epilepsy (n = 40) and with refractory focal epilepsy (n =
      69). Long-interval intracortical inhibition was measured by applying two supra
      threshold stimuli with an interstimulus interval of 50, 100, 150, 200 and 250 ms
      and calculating the ratio between the response to the second (test stimulus) and
      to the first (conditioning stimulus). In all subjects, the median response ratio
      showed inhibition at all interstimulus intervals. Using a mixed linear-effects
      model, we compared the long-interval intracortical inhibition response ratios
      between the different subject types. We conducted two analyses; one including
      data from the four centres and one excluding data from Centre 2, as the methods
      in this centre differed from the others. In the first analysis, we found no
      differences in long-interval intracortical inhibition between the different
      subject types. In all subjects, the response ratios at interstimulus intervals
      100 and 150 ms showed significantly more inhibition than the response ratios at
      50, 200 and 250 ms. Our second analysis showed a significant interaction between
      interstimulus interval and subject type (P = 0.0003). Post hoc testing showed
      significant differences between controls and refractory focal epilepsy at
      interstimulus intervals of 100 ms (P = 0.02) and 200 ms (P = 0.04). There were no
      significant differences between controls and refractory generalized epilepsy
      groups or between the refractory generalized and focal epilepsy groups. Our
      results do not support the body of previous work that suggests that long-interval
      intracortical inhibition is significantly reduced in refractory focal and genetic
      generalized epilepsy. Results from the second analysis are even in sharper
      contrast with previous work, showing inhibition in refractory focal epilepsy at
      200 ms instead of facilitation previously reported. Methodological differences,
      especially shorter intervals between the pulse pairs, may have contributed to our
      inability to reproduce previous findings. Based on our results, we suggest that
      long-interval intracortical inhibition as measured by transcranial magnetic
      stimulation and electromyography is unlikely to have clinical use as a biomarker
      of epilepsy.

PMID- 29340587
TI  - Subclinical device-detected atrial fibrillation and stroke risk: a systematic
      review and meta-analysis.
AB  - Aims: To determine stroke risk in subclinical atrial fibrillation (AF) and
      temporal association between subclinical AF and stroke. Methods and results:
      Pubmed/Embase was searched for studies reporting stroke in subclinical AF in
      patients with cardiac implantable electronic devices (CIEDs). After exclusions,
      11 studies were analysed. Of these seven studies reported prevalence of
      subclinical AF, two studies reported association between subclinical and clinical
      AF, seven studies reported stroke risk in subclinical AF, and five studies
      reported temporal relationship between subclinical AF and stroke. Subclinical AF
      was noted after CIEDs implant in 35% [interquartile range (IQR) 34-42] of
      unselected patients with pacing indication over 1-2.5 years. The definition and
      cut-off duration (for stroke risk) of subclinical AF varied across studies.
      Subclinical AF was strongly associated with clinical AF (OR 5.7, 95% CI 4.0-8.0,
      P < 0.001, I2 = 0%). The annual stroke rate in patients with subclinical AF >
      defined cut-off duration was 1.89/100 person-year (95% CI 1.02-3.52) with 2.4
      fold (95% CI 1.8-3.3, P < 0.001, I2 = 0%) increased risk of stroke as compared to
      patients with subclinical AF < cut-off duration (absolute risk was 0.93/100
      person-year). Three studies provided mean CHADS2 score. In these studies, with
      mean CHADS2 score of 2.1 +/- 0.1, subclinical AF was associated with annual
      stroke rate of 2.76/100 person-years (95% CI 1.46-5.23). After excluding patients
      without AF, only 17% strokes occurred in presence of ongoing AF. Subclinical AF
      was noted in 29% [IQR 8-57] within 30 days preceding stroke. Conclusion:
      Subclinical AF strongly predicts clinical AF and is associated with elevated
      absolute stroke risk albeit lower than risk described for clinical AF.

PMID- 29340589
TI  - Risk prediction by non-invasive coronary imaging: we are not there yet!

PMID- 29340588
TI  - Antimicrobial-Resistant Klebsiella pneumoniae Carriage and Infection in
      Specialized Geriatric Care Wards Linked to Acquisition in the Referring Hospital.
AB  - Background: Klebsiella pneumoniae is a leading cause of extended-spectrum beta
      lactamase (ESBL)-producing hospital-associated infections, for which elderly
      patients are at increased risk. Methods: We conducted a 1-year prospective cohort
      study, in which a third of patients admitted to 2 geriatric wards in a
      specialized hospital were recruited and screened for carriage of K. pneumoniae by
      microbiological culture. Clinical isolates were monitored via the hospital
      laboratory. Colonizing and clinical isolates were subjected to whole-genome
      sequencing and antimicrobial susceptibility testing. Results: K. pneumoniae
      throat carriage prevalence was 4.1%, rectal carriage 10.8%, and ESBL carriage
      1.7%, and the incidence of K. pneumoniae infection was 1.2%. The isolates were
      diverse, and most patients were colonized or infected with a unique phylogenetic
      lineage, with no evidence of transmission in the wards. ESBL strains carried
      blaCTX-M-15 and belonged to clones associated with hospital-acquired ESBL
      infections in other countries (sequence type [ST] 29, ST323, and ST340). One also
      carried the carbapenemase blaIMP-26. Genomic and epidemiological data provided
      evidence that ESBL strains were acquired in the referring hospital. Nanopore
      sequencing also identified strain-to-strain transmission of a blaCTX-M-15
      FIBK/FIIK plasmid in the referring hospital. Conclusions: The data suggest the
      major source of K. pneumoniae was the patient's own gut microbiome, but ESBL
      strains were acquired in the referring hospital. This highlights the importance
      of the wider hospital network to understanding K. pneumoniae risk and infection
      prevention. Rectal screening for ESBL organisms on admission to geriatric wards
      could help inform patient management and infection control in such facilities.

PMID- 29340591
TI  - Interactions of Coccinella novemnotata (Coleoptera: Coccinellidae) and Coccinella
      septempunctata (Coleoptera: Coccinellidae) While Foraging for Aphids.
AB  - The importation and establishment of Coccinella septempunctata L. (Coleoptera:
      Coccinellidae) in North America purportedly caused the displacement and local
      extirpation of the native ninespotted lady beetle, Coccinella novemnotata Herbst
      (Coleoptera: Coccinellidae), across most of its former range, and several reports
      have shown that C. septempunctata maintains competitive advantages over C.
      novemnotata. We investigated the role of aphid density on the retention time of
      these two species on fava bean plants, and the effect of con- versus
      heterospecific pairings of adult beetles on the foraging behavior of C.
      novemnotata. We found that aphid density did not affect C. novemnotata's
      retention time, but did affect the retention time of C. septempunctata, which
      left plants without aphids significantly faster than C. novemnotata.
      Additionally, C. septempunctata females left plants significantly faster than
      their male counterparts, whereas we observed no difference between the two sexes
      for C. novemnotata. Our test of pairs of beetles showed that C. novemnotata were
      together on plants more frequently than conspecific pairs of C. septempunctata
      and heterospecific pairs of beetles, and that all beetles were more likely to be
      found together on the aphid-infested plant versus the non-infested plant
      regardless of the pairs' composition. These results show that C. novemnotata
      spend more time foraging for aphids when aphids are scarce compared with C.
      septempunctata, and that C. novemnotata is less tolerant of occupying plants
      inhabited by C. septempunctata versus a conspecific beetle, adding additional
      mechanisms whereby C. septempunctata could outcompete C. novemnotata in the
      field.

PMID- 29340592
TI  - Neuroimmunomodulators in Neuroborreliosis and Lyme Encephalopathy.
AB  - Background: Lyme encephalopathy, characterized by nonspecific neurobehavioral
      symptoms including mild cognitive difficulties, may occur in patients with
      systemic Lyme disease and is often mistakenly attributed to central nervous
      system (CNS) infection. Identical symptoms occur in many inflammatory states,
      possibly reflecting the effect of systemic immune mediators on the CNS. Methods:
      Multiplex immunoassays were used to measure serum and cerebrospinal fluid (CSF)
      cytokines in patients with or without Lyme disease to determine if there are
      specific markers of active CNS infection (neuroborreliosis), or systemic
      inflammatory mediators associated with neurobehavioral syndromes. Results: CSF
      CXCL13 levels were elevated dramatically in confirmed neuroborreliosis (n = 8),
      less so in possible neuroborreliosis (n = 11) and other neuroinflammatory
      conditions (n = 44). Patients with Lyme (n = 63) or non-Lyme (n = 8)
      encephalopathy had normal CSF findings, but had elevated serum levels of
      interleukins 7, 17A, and 17F, thymic stromal lymphopoietin and macrophage
      inflammatory protein-alpha. Conclusions: CSF CXCL13 is a sensitive and specific
      marker of neuroborreliosis in individuals with Borrelia-specific intrathecal
      antibody production. However, it does not distinguish individuals strongly
      suspected of having neuroborreliosis, but lacking confirmatory intrathecal
      antibodies, from those with other neuroinflammatory conditions. Patients with
      mild cognitive symptoms occurring during acute Lyme disease, and/or after
      appropriate treatment, have normal CSF but elevated serum levels of T-helper 17
      markers and T-cell growth factors, which are also elevated in patients without
      Lyme disease but with similar symptoms. In the absence of CSF abnormalities,
      neurobehavioral symptoms appear to be associated with systemic inflammation, not
      CNS infection or inflammation, and are not specific to Lyme disease.

PMID- 29340590
TI  - Efficacy and Safety of Deep Brain Stimulation in Tourette Syndrome: The
      International Tourette Syndrome Deep Brain Stimulation Public Database and
      Registry.
AB  - Importance: Collective evidence has strongly suggested that deep brain
      stimulation (DBS) is a promising therapy for Tourette syndrome. Objective: To
      assess the efficacy and safety of DBS in a multinational cohort of patients with
      Tourette syndrome. Design, Setting, and Participants: The prospective
      International Deep Brain Stimulation Database and Registry included 185 patients
      with medically refractory Tourette syndrome who underwent DBS implantation from
      January 1, 2012, to December 31, 2016, at 31 institutions in 10 countries
      worldwide. Exposures: Patients with medically refractory symptoms received DBS
      implantation in the centromedian thalamic region (93 of 163 [57.1%]), the
      anterior globus pallidus internus (41 of 163 [25.2%]), the posterior globus
      pallidus internus (25 of 163 [15.3%]), and the anterior limb of the internal
      capsule (4 of 163 [2.5%]). Main Outcomes and Measures: Scores on the Yale Global
      Tic Severity Scale and adverse events. Results: The International Deep Brain
      Stimulation Database and Registry enrolled 185 patients (of 171 with available
      data, 37 females and 134 males; mean [SD] age at surgery, 29.1 [10.8] years
      [range, 13-58 years]). Symptoms of obsessive-compulsive disorder were present in
      97 of 151 patients (64.2%) and 32 of 148 (21.6%) had a history of self-injurious
      behavior. The mean (SD) total Yale Global Tic Severity Scale score improved from
      75.01 (18.36) at baseline to 41.19 (20.00) at 1 year after DBS implantation (P <
      .001). The mean (SD) motor tic subscore improved from 21.00 (3.72) at baseline to
      12.91 (5.78) after 1 year (P < .001), and the mean (SD) phonic tic subscore
      improved from 16.82 (6.56) at baseline to 9.63 (6.99) at 1 year (P < .001). The
      overall adverse event rate was 35.4% (56 of 158 patients), with intracranial
      hemorrhage occurring in 2 patients (1.3%), infection in 4 patients with 5 events
      (3.2%), and lead explantation in 1 patient (0.6%). The most common stimulation
      induced adverse effects were dysarthria (10 [6.3%]) and paresthesia (13 [8.2%]).
      Conclusions and Relevance: Deep brain stimulation was associated with symptomatic
      improvement in patients with Tourette syndrome but also with important adverse
      events. A publicly available website on outcomes of DBS in patients with Tourette
      syndrome has been provided.

PMID- 29340593
TI  - The Clinical Utility of Methicillin-Resistant Staphylococcus aureus (MRSA) Nasal
      Screening to Rule Out MRSA Pneumonia: A Diagnostic Meta-analysis With
      Antimicrobial Stewardship Implications.
AB  - Background: Recent literature has highlighted methicillin-resistant
      Staphylococcus aureus (MRSA) nasal screening as a possible antimicrobial
      stewardship program tool for avoiding unnecessary empiric MRSA therapy for
      pneumonia, yet current guidelines recommend MRSA therapy based on risk factors.
      The objective of this meta-analysis was to evaluate the diagnostic value of MRSA
      nasal screening in MRSA pneumonia. Methods: PubMed and EMBASE were searched from
      inception to November 2016 for English studies evaluating MRSA nasal screening
      and development of MRSA pneumonia. Data analysis was performed using a bivariate
      random-effects model to estimate pooled sensitivity, specificity, positive
      predictive value (PPV), and negative predictive value (NPV). Results: Twenty-two
      studies, comprising 5163 patients, met our inclusion criteria. The pooled
      sensitivity and specificity of MRSA nares screen for all MRSA pneumonia types
      were 70.9% and 90.3%, respectively. With a 10% prevalence of potential MRSA
      pneumonia, the calculated PPV was 44.8%, and the NPV was 96.5%. The pooled
      sensitivity and specificity for MRSA community-acquired pneumonia (CAP) and
      healthcare-associated pneumonia (HCAP) were 85% and 92.1%, respectively. For CAP
      and HCAP both the PPV and NPV increased, to 56.8% and 98.1%, respectively. In
      comparison, for MRSA ventilated-associated pneumonia, the sensitivity,
      specificity, PPV, and NPV were 40.3%, 93.7%, 35.7%, and 94.8%, respectively.
      Conclusion: Nares screening for MRSA had a high specificity and NPV for ruling
      out MRSA pneumonia, particularly in cases of CAP/HCAP. Based on the NPV, MRSA
      nares screening is a valuable tool for AMS to streamline empiric antibiotic
      therapy, especially among patients with pneumonia who are not colonized with
      MRSA.

PMID- 29340595
TI  - Clinical impact of rotor ablation in atrial fibrillation: a systematic review.
AB  - Aims: Rotor mapping and ablation have gained favour over the recent years as an
      emerging ablation strategy targeting drivers of atrial fibrillation (AF). Their
      efficacy, however, has been a topic of great debate with variable outcomes across
      centres. The aim of this study was to systematically review the recent medical
      literature to determine the medium-term outcomes of rotor ablation in patients
      with paroxysmal atrial fibrillation (PAF) and persistent atrial fibrillation
      (PeAF). Methods and results: A systematic search of the contemporary scientific
      literature (PubMed and EMBASE) was performed in August 2017. Only studies
      assessing arrhythmia-free survival from rotor ablation of AF were included. We
      used the random-effects model to assess the primary outcome of pooled medium-term
      single-procedure AF-free survival for both PAF and PeAF. Success rates from
      multiple procedures and complication rates were also examined. We included 11
      observational studies (4 PAF and 10 PeAF) with a total of 556 patients (166 PAF
      and 390 PeAF). Pooled single-procedure freedom from AF was 37.8% [95% confidence
      interval 5.6-86.3%] at a mean follow-up period of 13.8 +/- 1.8 months for PAF and
      59.2% (95% CI 41.4-74.9%) at a mean follow-up period of 12.9 +/- 6 months for
      PeAF. There was a marked heterogeneity between studies (I2 = 93.8% for PAF and
      88.3% for PeAF). The mean complication rate of rotor ablation among the reported
      studies was 3.4%. Conclusion: The wide variability in success rate between
      different centres performing rotor ablations suggests that the optimal ablation
      strategy, particularly targeting rotors, is unclear. Results from randomized
      studies are necessary before this technique can be considered as an established
      clinical tool.

PMID- 29340596
TI  - Commentary on: Effect of Botulinum Toxin A on Muscle Healing and its Implications
      in Aesthetic and Reconstructive Surgery.

PMID- 29340597
TI  - Managing dose-, damage- and data-rates in multi-frame spectrum-imaging.
AB  - As an instrument, the scanning transmission electron microscope is unique in
      being able to simultaneously explore both local structural and chemical
      variations in materials at the atomic scale. This is made possible as both types
      of data are acquired serially, originating simultaneously from sample
      interactions with a sharply focused electron probe. Unfortunately, such scanned
      data can be distorted by environmental factors, though recently fast-scanned
      multi-frame imaging approaches have been shown to mitigate these effects. Here,
      we demonstrate the same approach but optimized for spectroscopic data; we offer
      some perspectives on the new potential of multi-frame spectrum-imaging (MFSI) and
      show how dose-sharing approaches can reduce sample damage, improve
      crystallographic fidelity, increase data signal-to-noise, or maximize usable
      field of view. Further, we discuss the potential issue of excessive data-rates in
      MFSI, and demonstrate a file-compression approach to significantly reduce data
      storage and transmission burdens.

PMID- 29340598
TI  - The Risk of Skin Necrosis Following Hyaluronic Acid Filler Injection in Patients
      with a History of Cosmetic Rhinoplasty.
AB  - Background: As the number of patients using dermal filler for face augmentation
      increases, the number of adverse events associated with injection may increase.
      Unpredictable repositioning of blood vessels and a more tenuous blood supply in
      the operated nose may increase the risk of ischemia, necrosis and vascular
      embolism following the filler injection. Objectives: To highlight the importance
      of the patient's history of previous cosmetic procedures including rhinoplasty in
      the emergence of vascular complications. Methods: Our medical records over a two
      year period were reviewed retrospectively to identify all patients who were
      treated at our center for vascular complications associated with facial
      hyaluronic acid filler injections. In each case, the subject's demographic data
      (gender and age), habitual status, past medical and surgical history, the
      symptoms and clinical presentation at the first visit, the time interval between
      the injection and the onset of symptoms, injected filler material and brand,
      injection sites, the introduced treatment, and photographs were reviewed
      carefully. Results: A total of seven patients were identified, each developing
      skin necrosis following injection of the hyaluronic acid filler. All patients
      reported a cosmetic rhinoplasty more than three years ago. Conclusions: Our
      finding confirms the conjecture previously made in the literature and suggests
      that the distinctive vascularity of the nose and the surrounding area may cause
      filler augmentation induced vascular complications in patients whose vascular
      circulation has already been compromised by a previous nose surgery.

PMID- 29340599
TI  - A benchmark study of scoring methods for non-coding mutations.
AB  - Motivation: Detailed knowledge of coding sequences has led to different candidate
      models for pathogenic variant prioritization. Several deleteriousness scores have
      been proposed for the non-coding part of the genome, but no large-scale
      comparison has been realized to date to assess their performance. Results: We
      compared the leading scoring tools (CADD, FATHMM-MKL, Funseq2 and GWAVA) and some
      recent competitors (DANN, SNP and SOM scores) for their ability to discriminate
      assumed pathogenic variants from assumed benign variants (using the ClinVar,
      COSMIC and 1000 genomes project databases). Using the ClinVar benchmark, CADD was
      the best tool for detecting the pathogenic variants that are mainly located in
      protein coding gene regions. Using the COSMIC benchmark, FATHMM-MKL, GWAVA and
      SOMliver outperformed the other tools for pathogenic variants that are typically
      located in lincRNAs, pseudogenes and other parts of the non-coding genome.
      However, all tools had low precision, which could potentially be improved by
      future non-coding genome feature discoveries. These results may have been
      influenced by the presence of potential benign variants in the COSMIC database.
      The development of a gold standard as consistent as ClinVar for these regions
      will be necessary to confirm our tool ranking. Availability and implementation:
      The Snakemake, C++ and R codes are freely available from
      https://github.com/Oncostat/BenchmarkNCVTools and supported on Linux. Contact:
      damien.drubay@gustaveroussy.fr or stefan.michiels@gustaveroussy.fr. Supplementary
      information: Supplementary data are available at Bioinformatics online.

PMID- 29340600
TI  - Development and impact of a massive open online course (MOOC) for antimicrobial
      stewardship.
AB  - Background: The University of Dundee and the BSAC developed a massive open online
      course (MOOC) to address the global need for education to support antimicrobial
      stewardship in low- and middle-income countries. Methods: An interactive course,
      Antimicrobial Stewardship: Managing Antibiotic Resistance, was developed and
      delivered via the FutureLearn(c) platform. The course ran over four 6 week
      periods during 2015 and 2016 supported by educators and was evaluated via data on
      uptake and feedback from learners on impact on clinical practice. Results: In
      total, 32 944 people, 70% of them healthcare professionals, from 163 countries
      joined the course from Europe (49%), Asia (16%), Africa (13%), North America
      (9%), Australia (8%) and South America (5%). Between 33% and 37% of joiners in
      each run completed at least one step in any week of the course and 219
      participants responded to a post-course survey. The course was rated good or
      excellent by 208 (95%) of the participants, and 83 (38%) intended to implement
      stewardship interventions in their own setting. A follow-up survey 6 months later
      suggested that 49% had implemented such interventions. Conclusions: The MOOC has
      addressed a global learning need by providing education free at the point of
      access, and learning from its development will help others embarking upon similar
      educational solutions. Initial quantitative and qualitative feedback suggests it
      has engaged participants and complements traditional educational methods.
      Measuring its real impact on clinical practice remains a challenge. The
      FutureLearn(c) platform offers flexibility for MOOCs to be sustainable through
      modification to remove educator facilitation but maintain active participant
      discussion.

PMID- 29340601
TI  - How to treat borderline resectable pancreatic cancer: current challenges and
      future directions.
AB  - Borderline resectable pancreatic cancer (BRPC) is an advanced tumor in contact
      with the surrounding major vessels, making R0 resection difficult to achieve.
      Neoadjuvant treatment is expected to provide substantial local control and
      prolong survival. However, there is no standard treatment. I therefore conducted
      a strategic literature search from January 2013 to September 2017 and identified
      37 clinical studies of pancreatic cancer, including BRPC, to evaluate treatment
      interventions. Twenty (54%) studies were prospective. Neoadjuvant regimens were
      as follows: chemotherapy (CT) followed by chemoradiotherapy (CRT) or radiotherapy
      (RT) (n = 16, 43%), CT alone (n = 11, 30%), CRT alone (n = 9, 24%) and RT alone
      (n = 1, 3%). Radiotherapy was employed in 70% of the studies. Phase II studies
      were most frequent (55%), and we were unable to identify a Phase III study. The
      National Comprehensive Cancer Network's classifications were most frequently used
      as criteria for BRPC, although resectability status is not standardized.
      Radiological central review was used in three of eight multi-institutional
      studies. Assessing on-going or planned clinical trials for BRPC, administration
      of oxaliplatin, irinotecan, fluorouracil and leucovorin therapy or albumin-bound
      paclitaxel plus gemcitabine therapy, and randomized trials that evaluate the
      significance of CRT or RT combined with CT were identified as important topics
      for further consideration. Although standardization of classifications and
      improvement of infrastructure are required, a standard treatment of BRPC will
      likely be developed, which will improve prognosis in the near future because
      several important randomized trials are running.

PMID- 29340602
TI  - Emergence of blaCTX-M-55 associated with fosA, rmtB and mcr gene variants in
      Escherichia coli from various animal species in France.
AB  - Objectives: In Asian countries, blaCTX-M-55 is the second most common ESBL
      encoding gene. blaCTX-M-55 frequently co-localizes with fosA and rmtB genes on
      epidemic plasmids, which remain sporadic outside Asia. During 2010-13, we
      investigated CTX-M-55-producing Escherichia coli isolates and their co-resistance
      to fosfomycin, aminoglycosides, fluoroquinolones and colistin as part of a global
      survey of ESBLs in animals in France. Methods: blaCTX-M-55, fosA, rmtB and
      plasmidic quinolone and colistin resistance genes were characterized by PCR,
      sequencing and hybridization experiments. Plasmids were classified according to
      their incompatibility groups and subtypes. Genotyping was performed by MLST and
      repetitive extragenic palindromic sequence-based PCR. Results: Twenty-one E. coli
      isolates from bovines (n = 16), dogs (n = 2), horses (n = 2) and a monkey
      harboured blaCTX-M-55, were MDR and belonged to ST744 (n = 9) and 10 other
      clones. blaCTX-M-55 was mostly located on IncF (n = 19), but also on IncI1 (n =
      2) plasmids. On IncF33:A1:B1 plasmids, blaCTX-M-55 co-localized with the rmtB and
      aac(6')-Ib genes and in one isolate with the fosA3 allele. Ten IncF46:A-:B20
      plasmids, which were found in different clones from unrelated animals, also
      carried the mcr-3 gene. blaCTX-M-55-carrying IncF18:A-:B1 plasmids were found in
      different animal species from distinct locations and periods, and one
      additionally carried the fosA4 gene. One isolate harboured the mcr-1 gene, which
      did not co-localize with blaCTX-M-55. Conclusions: A large diversity of E. coli
      clones and plasmid types supported the spread of blaCTX-M-55, together with
      atypical resistance genes, in various animal species in France. fosA and rmtB
      genes are emerging among animals in Europe and this issue is of concern for
      public health.

PMID- 29340594
TI  - Keratan sulfate, a complex glycosaminoglycan with unique functional capability.
AB  - From an evolutionary perspective keratan sulfate (KS) is the newest
      glycosaminoglycan (GAG) but the least understood. KS is a sophisticated molecule
      with a diverse structure, and unique functional roles continue to be uncovered
      for this GAG. The cornea is the richest tissue source of KS in the human body but
      the central and peripheral nervous systems also contain significant levels of KS
      and a diverse range of KS-proteoglycans with essential functional roles. KS also
      displays important cell regulatory properties in epithelial and mesenchymal
      tissues and in bone and in tumor development of diagnostic and prognostic
      utility. Corneal KS-I displays variable degrees of sulfation along the KS chain
      ranging from non-sulfated polylactosamine, mono-sulfated and disulfated
      disaccharide regions. Skeletal KS-II is almost completely sulfated consisting of
      disulfated disaccharides interrupted by occasional mono-sulfated N
      acetyllactosamine residues. KS-III also contains highly sulfated KS disaccharides
      but differs from KS-I and KS-II through 2-O-mannose linkage to serine or
      threonine core protein residues on proteoglycans such as phosphacan and abakan in
      brain tissue. Historically, the major emphasis on the biology of KS has focused
      on its sulfated regions for good reason. The sulfation motifs on KS convey
      important molecular recognition information and direct cell behavior through a
      number of interactive proteins. Emerging evidence also suggest functional roles
      for the poly-N-acetyllactosamine regions of KS requiring further investigation.
      Thus further research is warranted to better understand the complexities of KS.

PMID- 29340603
TI  - Characterization of Antibiosis to Diabrotica speciosa (Coleoptera: Chrysomelidae)
      in Brazilian Maize Landraces.
AB  - Resistance to insect pests can be found in several native, landrace plants and
      can be an important alternative to conventional control methods. Diabrotica
      speciosa (Germar) (Coleoptera: Chrysomelidae) larvae are important maize (Zea
      mays L.) (Cyperales: Poaceae) root pests and finding native resistance in
      landraces would greatly contribute to maize-breeding programs aimed at
      controlling this pest. This study investigated whether the growth, survival,
      oviposition rhythm, fecundity, and fertility of D. speciosa are negatively
      influenced by specific maize landraces, and the existence of any morphological
      barriers in the roots that may correlate with plant resistance to the larval
      attack. Nineteen genotypes (17 landraces and 2 cultivars) were screened for
      antibiosis in assays that were conducted in the laboratory using seedling maize
      plants where the development time, longevity, weight, total survival, and sex
      ratio of adults were evaluated. Out of nineteen genotypes, eight were selected
      according to their resistance levels for an additional rearing study evaluating
      oviposition and fecundity. Landrace Perola and cultivar SCS 154-Fortuna were
      classified as resistant because they increased the maturation period from larva
      to adult and decreased survivorship; and the landrace Palha Roxa was also
      classified as resistant for showing a lower fertility rate than other landraces.
      Resistant landraces that were infested by D. speciosa larvae showed greater
      amounts of some morphological barriers comparing with uninfested plants. The
      landraces classified as resistant may be considered in future plant-breeding
      programs, aiming to develop resistant maize cultivars to D. speciosa larval
      attack.

PMID- 29340605
TI  - We can do better: a fresh look at echinocandin dosing.

PMID- 29340604
TI  - Transient recruitment of M-Ras GTPase to phagocytic cups in RAW264 macrophages
      during FcgammaR-mediated phagocytosis.
AB  - M-Ras, a member of the Ras superfamily, is known to be involved in diverse
      cellular processes. However, its involvement in FcgammaR-mediated phagocytosis
      remains unknown. We examined the spatiotemporal localization of M-Ras during the
      engulfment of IgG-opsonized erythrocytes (IgG-Es) in RAW264 macrophages. By the
      live-cell imaging of fluorescent protein-fused M-Ras, we found that M-Ras was
      localized to the membrane of phagocytic cups during the early stage of phagosome
      formation. Notably, ratiometric image analysis revealed that M-Ras was
      concentrated in the membrane of forming phagosomes. Moreover, our analysis of M
      Ras mutant expression showed that phagosome formation was significantly inhibited
      in cells expressing GDP-locked mutant M-Ras-S27N. In contrast, the expression of
      wild-type M-Ras or GTP-locked mutant M-Ras-G22V facilitated the uptake of IgG-Es.
      These data suggest that M-Ras is a novel component of the FcgammaR-mediated
      phagocytic pathway and may regulate phagosome formation in macrophages.

PMID- 29340606
TI  - Leaves, not roots or floral tissue, are the main site of rapid, external pressure
      induced ABA biosynthesis in angiosperms.
AB  - Rapid biosynthesis of abscisic acid (ABA) in the leaf, triggered by a decrease in
      cell volume, is essential for a functional stomatal response. However, it is not
      known whether rapid biosynthesis of ABA is also triggered in other plant tissues.
      Through the application of external pressure to flower, root, and leaf tissues,
      we test whether a reduction in cell volume can trigger rapid increases in ABA
      levels across the plant body in two species, Solanum lycopersicum and Passiflora
      tarminiana. Our results show that, in contrast to rapid ABA synthesis in the
      leaf, flower and root tissue did not show a significant, increase in ABA level in
      response to a drop in cell volume over a short time frame, suggesting that rapid
      ABA biosynthesis occurs only in leaf, not in flower or root tissues. A gene
      encoding the key, rate-limiting carotenoid cleavage enzyme (9-cis-epoxycarotenoid
      dioxygenase, NCED) in the ABA biosynthetic pathway in S. lycopersicum, NCED1, was
      upregulated to a lesser degree in flowers and roots compared with leaves in
      response to applied pressure. In both species, floral tissues contained
      substantially lower levels of the NCED substrate 9'-cis-neoxanthin than leaves,
      and this ABA precursor could not be detected in roots. Slow and minimal ABA
      biosynthesis was detected after 2 h in petals, indicating that floral tissue is
      capable of synthesizing ABA in response to sustained water deficit. Our results
      indicate that rapid ABA biosynthesis predominantly occurs in the leaves, and not
      in other tissues.

PMID- 29340607
TI  - Collection efficiency and acceptance maps of electron detectors for understanding
      signal detection on modern scanning electron microscopy.
AB  - Collection efficiency and acceptance maps of typical detectors in modern scanning
      electron microscopes (SEMs) were investigated. Secondary and backscattered
      electron trajectories from a specimen to through-the-lens and under-the-lens
      detectors placed on an electron optical axis and an Everhart-Thornley detector
      mounted on a specimen chamber were simulated three-dimensionally. The acceptance
      maps were drawn as the relationship between the energy and angle of collected
      electrons under different working distances. The collection efficiency
      considering the detector sensitivity was also estimated for the various working
      distances. These data indicated that the acceptance maps and collection
      efficiency are keys to understand the detection mechanism and image contrast for
      each detector in the modern SEMs. Furthermore, the working distance is the
      dominant parameter because electron trajectories are drastically changed with the
      working distance.

PMID- 29340608
TI  - Could Increasing Cancer Incidence Be Tied to Human Adaptation of Living in
      Extreme Environments?

PMID- 29340609
TI  - Impact of antibiotic stewardship programmes in Asia: a systematic review and meta
      analysis.
AB  - Background: The use of antibiotic stewardship programmes (ASPs) is increasing in
      Asia, but their effectiveness in reducing antibiotic consumption and their impact
      on clinical outcomes is not known. Objectives: To determine the impact of ASPs
      conducted in Asia on the consumption of antibiotics and on patients' clinical
      outcomes. Methods: We systematically searched the Embase and Medline (PubMed)
      databases for studies that compared antibiotic consumption or clinical outcomes
      of patients in an Asian hospital or clinic with an ASP (intervention) with those
      in a similar setting without an ASP (control). Meta-analyses of all-cause
      mortality and hospital-acquired infection (HAI) were performed using random
      effects models. Results: The search identified 77 studies of which 22 and 19
      reported antibiotic usage and cost, respectively. Among these, 20 (91%) studies
      reported reduced antibiotic usage and 19 (100%) reported cost savings in the
      intervention group. Duration of antibiotic therapy was reduced in six of seven
      studies in association with an ASP. Rates of all-cause mortality and HAI were not
      significantly different between the intervention and control groups. However,
      mortality rates were significantly improved by ASPs using drug monitoring, while
      HAI rates were also improved by ASPs that included infection control or hand
      hygiene programmes. Conclusions: In Asia, ASPs reduce antibiotic consumption in
      hospital and clinic settings and do not worsen clinical outcomes. The findings
      strongly support the broad implementation of antimicrobial stewardship
      interventions in hospital and clinic settings in Asia.

PMID- 29340610
TI  - Preclinical [18F]tetrafluoroborate-PET/CT imaging of pituitary gland hyperplasia.

PMID- 29340611
TI  - Treatment of Nasal Deviation With Underlying Bony Asymmetry Secondary to
      Augmentation Rhinoplasty in Asian Patients.
AB  - Background: In Asian patients, nasal deviation secondary to augmentation
      rhinoplasty may result from underlying bony asymmetry that was not corrected
      intraoperatively. Diagnosis and treatment of this condition are complicated by
      the masking effect of dorsal implants. Objectives: The authors applied computed
      tomography (CT) to examine the causes of nasal deviation after augmentation
      rhinoplasty. CT results were utilized in preoperative planning for revisional
      surgery. Methods: Fifteen women with nasal deviation after augmentation
      rhinoplasty and CT-confirmed bony asymmetry were included in a retrospective
      study. To correct nasal deviation, the authors performed revisional rhinoplasty
      with paramedian osteotomy and unilateral placement of extended spreader grafts at
      the concave side of the keystone region. For patients with concomitant glabella
      radix deviation, implants comprising expanded polytetrafluoroethylene or
      autologous fascia were placed. Results: Of the 15 patients with nasal bony
      asymmetry, 14 had developmental keystone asymmetry, and 1 had osteotomy-induced
      keystone deviation. Six patients had developmental glabella asymmetry. Patients
      received follow-up for an average of 11.2 months (range, 6-24 months). Revisional
      procedures were considered successful in 13 patients; 2 patients required
      additional surgery to address residual nasal deviation. Conclusions: CT is
      valuable for the diagnosis of post-augmentation nasal deviation owing to
      underlying bony asymmetry. Paramedian osteotomy with extended spreader grafting
      at the concave side of the keystone area and correction of the glabella-radix
      deviation are effective procedures to reposition the nasal axis along the midline
      of the face.

PMID- 29340612
TI  - Rice Field Spiders in China: A Review of the Literature.
AB  - Many laboratory and field studies have been conducted on rice field spiders in
      China. There are 375 species, 108 genera, and 22 families of rice field spiders
      distributed within the major rice growing areas and 17 dominant species. The
      biological and ecological characteristics of 17 rice field spider species have
      been reported in detail. The biology and ecology of these species show
      significant differences among regions, farmland habitats, and agricultural
      practices. Future research should focus on rice field habitat diversity,
      enhancing the insecticide resistance of dominant spider populations, implementing
      large-scale breeding of spiders and augmentative release, breeding more leaf
      dominant species, conducting biosafety assessment of spiders in transgenic crops.

PMID- 29340613
TI  - Biomass increase under zinc deficiency caused by delay of early flowering in
      Arabidopsis.
AB  - Plants generally produce more biomass when all nutrients are available in
      sufficient amounts. In addition to environmental constraints, genetic and
      developmental factors, such as the transition from vegetative to reproductive
      growth, restrict maximal biomass yield. Here, we report the peculiar observation
      that a subset of Arabidopsis thaliana accessions produced larger shoot rosette
      diameters when grown in zinc (Zn)-deficient conditions, compared with Zn
      sufficient conditions. This was associated with early flowering that restricted
      the leaf length under Zn sufficiency. Zinc deficiency repressed the expression of
      FLOWERING LOCUS T (FT), which encodes a major regulator of flowering. Repression
      or loss of FT increased the rosette diameter via a delay of the transition to
      flowering, a longer phase of leaf growth, and an increased leaf number. The
      transition to flowering reduced, but did not terminate, the proliferation of
      established leaves. The size of individual leaf mesophyll cells was not affected
      by Zn deficiency or by loss of FT, indicating that the larger rosette diameter
      was caused by maintained proliferation of vegetative tissue. As a consequence,
      early-flowering accessions under Zn deficiency grew to have larger rosette
      diameters due to a delay of flowering, which explains the unusual increase of
      vegetative biomass under nutrient deficiency.

PMID- 29340614
TI  - Association of Polygenic Risk Score With Cognitive Decline and Motor Progression
      in Parkinson Disease.
AB  - Importance: Genetic factors have a well-known influence on Parkinson disease (PD)
      susceptibility. The largest genome-wide association study (GWAS) identified 26
      independent single-nucleotide polymorphisms (SNPs) associated with PD risk. Among
      patients, the course and severity of symptom progression is variable, and little
      is known about the potential association of genetic factors with phenotypic
      variance. Objective: To assess whether GWAS-identified PD risk SNPs also have a
      cumulative association with the progression of cognitive and motor symptoms in
      patients with PD. Design, Setting, and Participants: This longitudinal population
      based cohort study of 285 patients of European ancestry with incident PD
      genotyped 23 GWAS SNPs. One hundred ninety-nine patients were followed up for a
      mean (SD) of 5.3 (2.1) years for progression (baseline: June 1, 2001, through
      November 31, 2007; follow-up: June 1, 2007, through August 31, 2013, with
      mortality surveillance through December 31, 2016); 57 patients had died or were
      too ill for follow-up, and 29 withdrew or could not be contacted. Movement
      disorder specialists repeatedly assessed PD symptom progression. Main Outcomes
      Measures: The combined association of PD risk loci, after creating a weighted
      polygenic risk score (PRS), with cognitive decline, motor progression, and
      survival, relying on Cox proportional hazards regression models and inverse
      probability weights to account for censoring. Results: Of the 285 patients
      undergoing genotyping, 160 were men (56.1%) and 125 were women (43.9%); the mean
      (SD) age at diagnosis was 69.1 (10.4) years. The weighted PRS was associated with
      significantly faster cognitive decline, measured by change in the Mini-Mental
      State Examination (hazard ratio [HR] per 1 SD, 1.44; 95% CI, 1.00-2.07). The PRS
      was also associated with faster motor decline, measured by time to Hoehn & Yahr
      Scale stage 3 (HR, 1.34; 95% CI, 1.00-1.79) and change in Unified Parkinson's
      Disease Rating Scale part III score (HR, 1.42; 95% CI, 1.00-2.01). Conclusions
      and Relevance: Susceptibility SNPs for PD combined with a cumulative PRS were
      associated with faster motor and cognitive decline in patients. Thus, these
      genetic markers may be associated with not only PD susceptibility but also
      disease progression in multiple domains.

PMID- 29340615
TI  - A simple method to detect the tandem repeat of the cyp51A promoter in azole
      resistant strains of Aspergillus fumigatus.
AB  - We designed primers and cycling probes to detect the tandem repeat (TR) of cyp51A
      promoter in Aspergillus fumigatus. A control-probe was designed to anneal to the
      outside of the TR region, whereas a TR-probe was designed to anneal to the inside
      of the TR region. For amplification and probe-hydrolysis detection, the
      CycleavePCR system was used. Although the difference between Ct values of the
      wild-type genome for the control-probe and the TR-probe was around -0.1, the
      difference between Ct values of TR-harboring strains was around 0.7. These data
      indicate that this is a simple method to detect TR in azole-resistant A.
      fumigatus.

PMID- 29340616
TI  - PyChimera: use UCSF Chimera modules in any Python 2.7 project.
AB  - Motivation: UCSF Chimera is a powerful visualization tool remarkably present in
      the computational chemistry and structural biology communities. Built on a C++
      core wrapped under a Python 2.7 environment, one could expect to easily import
      UCSF Chimera's arsenal of resources in custom scripts or software projects.
      Nonetheless, this is not readily possible if the script is not executed within
      UCSF Chimera due to the isolation of the platform. UCSF ChimeraX, successor to
      the original Chimera, partially solves the problem but yet major upgrades need to
      be undergone so that this updated version can offer all UCSF Chimera features.
      Results: PyChimera has been developed to overcome these limitations and provide
      access to the UCSF Chimera codebase from any Python 2.7 interpreter, including
      interactive programming with tools like IPython and Jupyter Notebooks, making it
      easier to use with additional third-party software. Availability and
      implementation: PyChimera is LGPL-licensed and available at
      https://github.com/insilichem/pychimera. Contact: jaime.rodriguezguerra@uab.cat
      or jeandidier.marechal@uab.cat. Supplementary information: Supplementary data are
      available at Bioinformatics online.

PMID- 29340617
TI  - Facial Herpes Zoster Following Rhinoplasty: A Rare Complication.

PMID- 29340619
TI  - Recurrent serious infections in patients with rheumatoid arthritis-results from
      the British Society for Rheumatology Biologics Register.
AB  - Objectives: To establish the rate of recurrent infection in RA patients recruited
      to the British Society for Rheumatology Biologics Register - Rheumatoid
      Arthritis. Secondary objectives were to establish whether the organ class of
      index infection predicted future serious infection (SI). Methods: Using data from
      the British Society for Rheumatology Biologics Register - Rheumatoid Arthritis, a
      prospective observational cohort, we identified patients with at least one
      episode of SI. Incidence rates of SI, recurrent SI within the same organ class as
      the index infection and recurrent SI (of any class) were calculated. A Cox
      proportional hazards model was used to identify predictors of SI. Results: In
      total, 5289 subjects with at least one SI contributing 19 431 patient-years
      follow-up were studied. The baseline annual rate of first SI was 4.6% (95% CI:
      4.5, 4.7), increasing to 14.1% (95% CI: 13.5, 14.8) following an index infection.
      Respiratory infections were the most frequent (44% of all events). Recurrent
      infections mirrored the organ class of the index infection. Sepsis, increasing
      age and polypharmacy were significant predictors of infection recurrence in a
      fully adjusted model. The system class of index infection was associated with the
      risk of a recurrent event; subjects who experienced sepsis had the highest risk
      of subsequent SI within 12 months, 19.7% (95% CI: 15.1, 25.7). Conclusion:
      Recurrent infections in RA are common. Understanding patterns and predictors of
      recurrent infection together with the differential infection risk associated with
      immunosuppressive agents will help personalize RA care, tailor treatment choices
      better and mitigate against episodes of SI.

PMID- 29340618
TI  - Mitochondrial Toxicity.
AB  - Recent decades have seen a rapid increase in reported toxic effects of drugs and
      pollutants on mitochondria. Researchers have also documented many genetic
      differences leading to mitochondrial diseases, currently reported to affect ~1
      person in 4,300, creating a large number of potential gene-environment
      interactions in mitochondrial toxicity. We briefly review this history, and then
      highlight cutting-edge areas of mitochondrial research including the role of
      mitochondrial reactive oxygen species in signaling; increased understanding of
      fundamental biological processes involved in mitochondrial homeostasis (DNA
      maintenance and mutagenesis, mitochondrial stress response pathways, fusion and
      fission, autophagy and biogenesis, and exocytosis); systemic effects resulting
      from mitochondrial stresses in specific cell types; mitochondrial involvement in
      immune function; the growing evidence of long-term effects of mitochondrial
      toxicity; mitochondrial-epigenetic cross-talk; and newer approaches to test
      chemicals for mitochondrial toxicity. We also discuss the potential importance of
      hormetic effects of mitochondrial stressors. Finally, we comment on future areas
      of research we consider critical for mitochondrial toxicology, including
      increased integration of clinical, experimental laboratory, and epidemiological
      (human and wildlife) studies; improved understanding of biomarkers in the human
      population; and incorporation of other factors that affect mitochondria, such as
      diet, exercise, age, and nonchemical stressors.

PMID- 29340620
TI  - Delivery of Tapasin-modified CTL epitope peptide via cytoplasmic transduction
      peptide induces CTLs by JAK/STAT signaling pathway in vivo.
AB  - Hepatitis B virus (HBV)-specific cytotoxic T lymphocytes (CTLs) play a vital role
      in viral control and clearance. Recent studies have elucidated that Tapasin, an
      endoplasmic reticulum chaperone, is a well-known molecule that appears to be
      essential in peptide-loading process. The Janus kinase/signal transducers and
      activators of transcription (JAK/STAT) pathway plays an important role in immune
      response regulation and cytokines secretion. We have previously verified that
      fusion protein CTP-HBcAg18-27-Tapasin could facilitate the maturation of bone
      marrow derived dendritic cells and enhance specific CTLs responses in vitro,
      which might be associated with the activation of JAK/STAT signaling pathway. To
      further explore whether JAK/STAT signaling pathway participated in specific
      immune responses mediated by CTP-HBcAg18-27-Tapasin, we suppressed the JAK/STAT
      pathway with pharmacological inhibitor (AG490) in vivo. Our studies showed that
      the number of IFN-gamma+-CD8+ T cells was decreased significantly compared with
      other groups after being blocked by AG490. The percentage of IFN-gamma+-CD4+ T
      cells and IL-2-CD4+ T cells was also decreased. Moreover, lower expression levels
      of Jak2, Tyk2, STAT1, and STAT4 were detected in AG490 group. In addition, the
      secretion levels of Th1-like cytokines were decreased and a weaker specific T
      cell response was observed in AG490 group. Furthermore, the levels of HBV DNA and
      HBsAg in serum and expression levels of HBsAg and HBcAg in liver tissues were
      elevated after this pathway was inhibited in HBV transgenic mice. These results
      demonstrate that the JAK/STAT signaling pathway participates in Th1-oriented
      immune response induced by CTP-HBcAg18-27-Tapasin and this might provide a
      theoretical basis for HBV immunotherapy.

PMID- 29340621
TI  - Examining Exposure Assessment in Shift Work Research: A Study on Depression Among
      Nurses.
AB  - Introduction: Coarse exposure assessment and assignment is a common issue facing
      epidemiological studies of shift work. Such measures ignore a number of exposure
      characteristics that may impact on health, increasing the likelihood of biased
      effect estimates and masked exposure-response relationships. To demonstrate the
      impacts of exposure assessment precision in shift work research, this study
      investigated relationships between work schedule and depression in a large survey
      of Canadian nurses. Methods: The Canadian 2005 National Survey of the Work and
      Health of Nurses provided the analytic sample (n = 11450). Relationships between
      work schedule and depression were assessed using logistic regression models with
      high, moderate, and low-precision exposure groupings. The high-precision grouping
      described shift timing and rotation frequency, the moderate-precision grouping
      described shift timing, and the low-precision grouping described the
      presence/absence of shift work. Final model estimates were adjusted for the
      potential confounding effects of demographic and work variables, and bootstrap
      weights were used to generate sampling variances that accounted for the survey
      sample design. Results: The high-precision exposure grouping model showed the
      strongest relationships between work schedule and depression, with increased odds
      ratios [ORs] for rapidly rotating (OR = 1.51, 95% confidence interval [CI] = 0.91
      2.51) and undefined rotating (OR = 1.67, 95% CI = 0.92-3.02) shift workers, and a
      decreased OR for depression in slow rotating (OR = 0.79, 95% CI = 0.57-1.08)
      shift workers. For the low- and moderate-precision exposure grouping models, weak
      relationships were observed for all work schedule categories (OR range 0.95 to
      0.99). Conclusions: Findings from this study support the need to consider and
      collect the data required for precise and conceptually driven exposure assessment
      and assignment in future studies of shift work and health. Further research into
      the effects of shift rotation frequency on depression is also recommended.

PMID- 29340622
TI  - Comment on: Cryofibrinogenaemia-a neglected disease.

PMID- 29340624
TI  - Early and long-term outcomes of mitral valve repair for Barlow's disease: a
      single-centre 16-year experience.
AB  - OBJECTIVES: Following mitral valve repair for Barlow's disease, recurrent mitral
      regurgitation (MR) is believed to occur frequently and is mainly attributed to
      disease progression. METHODS: Between January 2000 and December 2015, 180
      patients (40% women, mean age 58.7 +/- 13.5 years) with Barlow's disease
      underwent mitral valve repair. To provide a longitudinal assessment of mitral
      valve repair durability, a multistate model for interval-censored observations (4
      states: 1, Grade 0/1+ MR; 2, Grade 2+ MR; 3, Grade 3+/4+ MR; 4,
      reintervention/death) was developed. The mechanism of recurrent MR was assessed
      echocardiographically. RESULTS: Early mortality was 1.7%. After hospital
      discharge, 6 late reinterventions were performed. With death as a competing risk,
      the 10-year overall reintervention-free survival and reintervention rates were
      79.8% (95% confidence interval 72.7-87.6%) and 4.5% (95% confidence interval 2.0
      10.2%), respectively. Echocardiographic follow-up was available for 165 (93%) of
      hospital survivors with a total of 480 examinations. The incidence of both
      recurrent Grade 2+ and Grade 3+/4+ MR was relatively low up to 10 years after
      surgery. Grade 2+ MR did not always progress to higher regurgitation grade during
      the follow-up period. Grade 3+/4+ regurgitation was highly associated with valve
      related morbidity and mortality. Recurrent MR (>=Grade 2+) was predominantly
      related to the technical aspects of valve repair. CONCLUSIONS: Despite the
      complex valve abnormalities observed in patients with Barlow's disease, mitral
      valve repair can be performed with good early and late outcomes and low rates of
      recurrence of MR up to 10 years after surgery. Early and late valve repair
      durability is good and remains stable over time, suggesting that underlying
      disease progression has limited clinical significance.

PMID- 29340623
TI  - Pharmacokinetics of rituximab and clinical outcomes in patients with anti
      neutrophil cytoplasmic antibody associated vasculitis.
AB  - Objectives: To study the determinants of the pharmacokinetics (PK) of rituximab
      (RTX) in patients with ANCA-associated vasculitis (AAV) and its association with
      clinical outcomes. Methods: This study included data from 89 patients from the
      RTX in AAV trial who received the full dose of RTX (four weekly infusions of 375
      mg/m2). RTX was quantified at weeks 2, 4, 8, 16 and 24, and summarized by
      computing the trapezoidal area under the curve. We explored potential
      determinants of the PK-RTX, and analysed its association with clinical outcomes:
      achievement of remission at 6 months, duration of B-cell depletion and time to
      relapse in patients who achieved complete remission. Results: RTX serum levels
      were significantly lower in males and in newly diagnosed patients, and negatively
      correlated with body surface area, baseline B-cell count and degree of disease
      activity. In multivariate analyses, the main determinants of PK-RTX were sex and
      new diagnosis. Patients reaching complete remission at month 6 had similar RTX
      levels compared with patients who did not reach complete remission. Patients with
      higher RTX levels generally experienced longer B-cell depletion than patients
      with lower levels, but RTX levels at the different time points and area under the
      curve were not associated with time to relapse. Conclusion: Despite the body
      surface-area-based dosing protocol, PK-RTX is highly variable among patients with
      AAV, its main determinants being sex and newly diagnosed disease. We did not
      observe any relevant association between PK-RTX and clinical outcomes. The
      monitoring of serum RTX levels does not seem clinically useful in AAV.

PMID- 29340625
TI  - Seen through the patients' eyes: surgical safety and checklists.
AB  - Objective: We sought to explore the views patients have towards surgical safety
      and checklists. As a secondary aim, we explored if previous experience of error
      or other patient characteristics influence these views. Design: A cross-sectional
      survey study design was applied. Participants: The Flemish Patients' Platform
      network and social media were used to recruit participants. Main outcome
      measure(s): An 11-item questionnaire was designed to assess the following
      constructs: perception of surgical safety, attitudes towards the WHO surgical
      safety checklist and attitudes regarding checklist usage. Results: Respondents'
      view (N = 444) on the risk of an adverse event showed considerable variation.
      Respondents were positive towards the checklist, strongly agreeing that it would
      impact positively on their safety. However, this positive perception did not
      translate into an attitude where patients will actively inform themselves whether
      a checklist is used. The majority of respondents have no difficulty with
      repetitive verification of identity, procedure and location of the surgery.
      Respondents with a clinical background were the least anxious. Views were divided
      regarding hearing discussions around blood loss or airway problems. Conclusions:
      Patients perceive the checklist as a reliable safety tool. They do not mind
      repetitive verification of identity and procedure. However, hearing staff
      discussing specific, explicit, risks could cause anxiousness in some patients.
      Building a supportive and collaborative environment is needed to involve and
      empower patients to contribute in the realization of a safe hospital environment.

PMID- 29340626
TI  - Suppression of NLRP3 inflammasome by oral treatment with sulforaphane alleviates
      acute gouty inflammation.
AB  - Objective: The aetiology of gout is closely linked to the deposition of
      monosodium uric acid (MSU) crystals and the consequent activation of the NOD-like
      receptor family, pyrin domain containing 3 (NLRP3) inflammasome. In this study,
      we investigated whether oral administration of an NLRP3 inhibitor would be
      effective to attenuate the symptoms of gout. Methods: The effects of oral
      administration with sulforaphane (SFN) were examined in two mouse models of acute
      gout induced by injection of MSU crystals into footpads or air pouch. The
      production of caspase-1 (p10) and IL-1beta was examined by immunoblotting and
      ELISA as hallmarks of NLRP3 inflammasome activation. Results: Oral administration
      of SFN attenuated MSU crystal-induced swelling and neutrophil recruitment in a
      mouse foot acute gout model, correlating with the suppression of the NLRP3
      inflammasome activation in foot tissues. Consistently, oral administration of SFN
      blocked MSU-crystal-induced activation of the NLRP3 inflammasome in a mouse air
      pouch gout model. SFN suppressed NLRP3 inflammasome activation induced by MSU
      crystals, adenosine triphosphate and nigericin but not by poly(dA:dT) in primary
      mouse macrophages, independent of the reactive oxygen species pathway. SFN
      inhibited ligand-independent activation of the NLRP3 inflammasome, suggesting
      that SFN may act directly on the NLRP3 inflammasome complex. Conclusion: Oral
      administration of SFN effectively alleviated acute gouty inflammation by
      suppression of the NLRP3 inflammasome. Our results provide a novel strategy in
      which oral treatment with SFN may be beneficial in preventing acute attacks of
      gout.

PMID- 29340627
TI  - In search of a diagnostic test for polymyalgia rheumatica: is positron emission
      tomography the answer?

PMID- 29340628
TI  - The Importance of Umbilical Blood Supply and Umbilical Delay in Secondary
      Abdominoplasty: A Case Report.
AB  - The umbilicus is an important aesthetic landmark of the abdomen. It possesses a
      dual blood supply that allows it to survive either on its stalk if the skin
      surrounding the umbilicus is incised, or through the surrounding subdermal
      circulation if the stalk is transected. This is an important concept to consider
      in order to avoid umbilical ischemia and necrosis during abdominoplasty,
      especially if there is any past surgical history suggesting alteration to its
      blood supply. This case study depicts this importance and the importance of the
      use of delay in order to improve perfusion to the umbilicus prior to secondary
      abdominoplasty. In this case, a 47-year-old woman had undergone abdominoplasty
      two years previously and requested further improvement of her abdominal contour.
      At her original operation, the umbilical stalk was transected during hernia
      repair and the umbilicus was "floated" inferiorly to its new position. Thus,
      during her second revisionary abdominoplasty, it was crucial to consider the
      adequacy of umbilical blood supply to minimize and avoid the possibility of
      ischemic necrosis of the umbilicus due to alteration of umbilical blood supply.
      Therefore, a delay procedure of the umbilicus was performed. This case report
      emphasizes the need for proper consideration of umbilical blood supply, and delay
      of the umbilicus if alterations to its normal blood supply are known to be
      present or suspected to exist.

PMID- 29340629
TI  - DEVELOPMENT OF A SET OF MESH-BASED AND AGE-DEPENDENT CHINESE PHANTOMS AND
      APPLICATION FOR CT DOSE CALCULATIONS.
AB  - Phantoms for organ dose calculations are essential in radiation protection
      dosimetry. This article describes the development of a set of mesh-based and age
      dependent phantoms for Chinese populations using reference data recommended by
      the Chinese government and by the International Atomic Energy Agency (IAEA).
      Existing mesh-based RPI adult male (RPI-AM) and RPI adult female (RPI-AF)
      phantoms were deformed to form new phantoms according to anatomical data for the
      height and weight of Chinese individuals of 5 years old male, 5 years old female,
      10 years old male, 10 years old female,15 years old male, 15 years old female,
      adult male and adult female-named USTC-5 M, USTC-5F, USTC-10M, USTC-10F, USTC
      15M, USTC-15F, USTC-AM and USTC-AF, respectively. Following procedures to ensure
      the accuracy, more than 120 organs/tissues in each model were adjusted to match
      the Chinese reference parameters and the mass errors were within 0.5%. To
      demonstrate the usefulness, these new set of phantoms were combined with a fully
      validated model of the GE LightSpeed Pro 16 multi-detector computed tomography
      (MDCT) scanner and the GPU-based ARCHER Monte Carlo code to compute organ doses
      from CT examinations. Organ doses for adult models were then compared with the
      data of RPI-AM and RPI-AF under the same conditions. The absorbed doses and the
      effective doses of RPI phantoms are found to be lower than these of the USTC
      adult phantoms whose body sizes are smaller. Comparisons for the doses among
      different ages and genders were also made. It was found that teenagers receive
      more radiation doses than adults do. Such Chinese-specific phantoms are clearly
      better suited in organ dose studies for the Chinese individuals than phantoms
      designed for western populations. As already demonstrated, data derived from age
      specific Chinese phantoms can help CT operators and designers to optimize image
      quality and doses.

PMID- 29340630
TI  - Sutureless prosthesis for failed small Mitroflow valves: the Perceval-after
      Mitroflow procedure.
AB  - Because of its favourable haemodynamic characteristics and easy implantability,
      Mitroflow aortic valve bioprosthesis has been the valve of choice for many
      surgeons in patients with small aortic annulus. Disappointingly, early structural
      valve deterioration and high transvalvular gradients have been reported mostly in
      older patients with small prostheses. Reimplanting a new stented prosthesis
      sutured in a narrow and damaged annulus is technically challenging and demanding
      mainly in high-risk patients. Valve-in-valve transcatheter aortic valve
      implantation has been proposed as a viable option; however, it presents
      significant limitations because of residual high transprosthetic pressure
      gradients and risk of coronary occlusion. We report a series of 8 patients, with
      medium-term follow-up, who underwent successful Perceval-S surgical sutureless
      aortic implant after the removal of a degenerated small Mitroflow valve. No early
      mortality occurred, but 1 patient died 4 months postoperatively due to
      gastrointestinal disease. No major complications occurred. Early and mid-term
      postoperative pressure gradients were low (mean gradients 13.1 +/- 3.3 mmHg and
      10.2 +/- 3.8 mmHg, respectively). In operable patients with a degenerated
      Mitroflow valve, these favourable clinical and haemodynamic results suggest that
      the sutureless solution is a simple, valid and safer alternative to conventional
      redo valve replacement or to valve-in-valve transcatheter aortic valve
      implantation.

PMID- 29340631
TI  - A better understanding of ambulance personnel's attitude towards real-time
      resuscitation feedback.
AB  - Objective: High-quality chest compressions during cardiopulmonary resuscitation
      (CPR) play a significant role in surviving cardiac arrest. Chest-compression
      quality can be measured and corrected by real-time CPR feedback devices, which
      are not yet commonly used. This article looks at the acceptance of such systems
      in comparison of equipped and unequipped personnel. Design: Two groups of
      emergency medical services' (EMS) personnel were interviewed using standardized
      questionnaires. Setting: The survey was conducted in the German cities Dortmund
      and Munster. Participants: Overall, 205 persons participated in the survey: 103
      paramedics and emergency physicians from the Dortmund fire service and 102
      personnel from the Munster service. Intervention: The staff of the Dortmund
      service were not equipped with real-time feedback systems. The test group of
      equipped personnel of the ambulance service of Munster Fire brigade uses real
      time feedback systems since 2007. Main outcome measure: What is the acceptance
      level of real-time feedback systems? Are there differences between equipped and
      unequipped personnel? Results: The total sample is receptive towards real-time
      feedback systems. More than 80% deem the system useful. However, this study
      revealed concerns and prejudices by unequipped personnel. Negative ratings are
      significantly lower at the Munster site that is experienced with the use of the
      real-time feedback system in contrast to the Dortmund site where no such
      experience exists-the system's use in daily routine results in better evaluation
      than the expectations of unequipped personnel. Conclusions: Real-time feedback
      systems receive overall positive ratings. Prejudices and concerns seem to
      decrease with continued use of the system.

PMID- 29340632
TI  - Developing a set of indicators to monitor quality in ambulatory diabetes care
      using a modified Delphi panel process.
AB  - Objective: There is a large evidence to practice gap in diabetes care with
      limited performance assessments that capture the full spectrum of care delivery.
      Our study aimed to develop a set of ambulatory diabetes quality indicators across
      six domains (effectiveness, safety, patient-centered, timely, equitable and
      efficient) to provide a broad view of quality. Design: A modified Delphi panel
      process was conducted. Phase I involved compiling a list of indicators through
      literature review and generation of patient and healthcare provider-derived
      indicators through interviews and surveys, respectively. Phase II involved
      panelists rating indicators using the Agency for Healthcare Research and Quality
      measure attributes on 9-point Likert scale, attending a face-to-face meeting
      followed by re-rating, and final ranking. Setting: This study was conducted
      across five adult academic medical centers affiliated with the University of
      Toronto. Participants: A multi-disciplinary Delphi panel (n = 16) including
      patients was assembled. Main Outcome measure: For indicator advancement for
      ranking, >=75% of panelists' responses in the top tertile (between 7 and 9) with
      a median composite score of >=7 was required. Results: There were 202 indicators
      included in the Delphi panel process including 171 from a comprehensive
      literature review, 14 from patient interviews, and 17 from healthcare provider
      surveys. Following the first round, 40 indicators proceeded directly to ranking,
      while 162 indicators were re-rated and distilled down to 12 for ranking. In the
      final ranking round, the 52 indicators were reduced to 35 including 13 effective,
      10 safe, 6 patient-centered, 1 equitable, 3 efficient and 2 timely indicators.
      Conclusion: Thirty-five selected indicators developed with broad stakeholder
      engagement can be used to monitor quality in diabetes care.

PMID- 29340633
TI  - Kinking of an open stent graft after total arch replacement with the frozen
      elephant technique for acute Type A aortic dissection.
AB  - Recently, in Japan, the J Graft Open Stent Graft (JOSG) was commercialized for
      surgical repair of an aortic aneurysm and aortic dissection and the frozen
      elephant trunk technique was applied. Kinking of the JOSG is a rare adverse event
      that requires additional intervention. We experienced 2 patients who developed
      kinking of a JOSG after translocated total arch replacement with the frozen
      elephant trunk technique for acute Type A aortic dissection. Both patients had
      intermittent claudication with a decreased ankle-brachial pressure index after
      the operation. Computed tomography angiography showed kinking between the non
      stent and stent parts of the JOSG. Therefore, we performed endovascular repair. A
      severely angulated arch preserved by a translocated technique may lead to kinking
      of a JOSG. This suggests that the removed non-stent part should be as short as
      possible to prevent kinking of the JOSG.

PMID- 29340634
TI  - Efficient decellularization for bovine pericardium with extracellular matrix
      preservation and good biocompatibility.
AB  - OBJECTIVES: In this study, we sought to explore an efficient decellularization
      protocol for bovine pericardia with better extracellular matrix preservation and
      good biocompatibility. METHODS: Bovine pericardia were decellularized by sodium
      dodecyl sulphate (SDS), SDS + sodium deoxycholate (SD), Triton X-100 (TX), TX +
      SD (TS), freeze-thaw cycles + SDS + SD (FSS) and freeze-thaw cycles + TX + SD
      (FTS), respectively. Untreated pericardia were used as native control.
      Histological examination, residual cellular content analysis, biochemical and
      biomechanical evaluations and cytotoxicity assay were performed to investigate
      decellularization efficiency, xenoantigens removal, extracellular matrix
      preservation and biocompatibility. In vivo biocompatibility was evaluated using a
      subcutaneous implantation method in rats. RESULTS: Among these protocols, FSS and
      FTS protocols were the most effective methods to remove both the DNA material and
      the galactose-alpha-1,3-galactose antigen. TX, TS and FTS bovine pericardia
      maintained the collagen content and had no cytotoxicity to human umbilical vein
      endothelial cells. The contents of elastin and glycosaminoglycan were lost to
      different degrees after decellularization, with the highest content of
      preservation with TX, followed by TS and FTS. Consistently, no significant
      difference was found between native bovine pericardia and TX, TS or FTS bovine
      pericardia. In vivo, FTS implants had minimal infiltration of macrophages and T
      lymphocytes, with no histological evidence of peri-implant necrosis and
      calcification. CONCLUSIONS: These results suggested that the FTS protocol showed
      optimal decellularization results with better extracellular matrix preservation
      and good biocompatibility. It may be a suitable protocol for producing a suitable
      scaffold for heart tissue engineering.

PMID- 29340635
TI  - Nutrient digestibility response to sugarcane bagasse addition and corn particle
      size in normal and high Na diets for broilers.
AB  - Improving diet digestibility is important to the broiler industry. Therefore,
      this study focused on optimizing the physical structure of feed ingredients and
      addition of dietary fiber as strategies to improve nutrient digestibility in low
      and high sodium diets. A total of 672 day-old Ross 308 male broilers was
      allocated to 48 pens using a 2 * 2 * 2 factorial arrangement of treatments with 2
      particle sizes of corn (coarse 3,576 MUm or fine 1,113 MUm geometric mean
      diameter), 2 levels of sugarcane bagasse (SB) (0 or 2%), and 2 levels of Na (0.16
      or 0.4%). Protein digestibility coefficient was measured using pooled distal
      ileal digesta of 3 birds per pen on d 24. Meanwhile, starch and gross energy
      digestibility coefficients were measured using pooled duodenal, distal jejunal,
      and distal ileal digesta of 3 birds per pen on d 24. Coarsely ground corn (CC)
      resulted in improved ileal protein digestibility (P < 0.05). Addition of 2% SB
      increased starch digestibility in the duodenum (P < 0.05), distal jejunum (P <
      0.001), and distal ileum (P < 0.001), and increased protein digestibility in
      distal ileum (P < 0.01). A significant particle size * SB * Na interaction was
      observed for ileal energy digestibility (P < 0.05). The SB increased ileal energy
      digestibility only in birds fed the diet with finely ground corn (FC) and 0.16%
      Na. These findings demonstrate that SB and CC are able to improve nutrient
      digestibility. It can be recommended for the poultry industry to use SB and
      coarsely ground corn in feed to improve the utilization of nutrients.

PMID- 29340636
TI  - Changes in Socioeconomic Differences in Hospital Days With Age: Cumulative
      Disadvantage, Age-as-Leveler, or Both?
AB  - Objectives: Length of hospital stay is inversely associated with socioeconomic
      status (SES). It is less clear whether socioeconomic disparities in numbers of
      hospital days diverge or converge with age. Method: Longitudinal linked Finnish
      registry data (1988-2007) from 137,653 men and women aged 50-79 years at the end
      of 1987 were used. Trajectories of annual total hospital days by education,
      household income, and occupational class were estimated using negative binomial
      models. Results: Men and women with higher education, household income, and
      occupational class had fewer hospital days in 1988 than those with lower SES.
      Hospital days increased between 1988 and 2007. For some age groups, higher SES
      was associated with a faster annual rate of increase, resulting in narrowing rate
      ratios of hospital days between SES groups (relative differences); the rate
      ratios remained stable for other groups. Absolute SES differences in numbers of
      hospital days appeared to diverge with age among those aged 50-69 years at
      baseline, but converge among those aged 70-79 years at baseline. Discussion: The
      hypotheses that socioeconomic disparities in health diverge or converge with age
      may not be mutually exclusive; we demonstrated convergence/maintenance in
      relative differences for all age groups, but divergence or convergence in
      absolute differences depending on age.

PMID- 29340637
TI  - Cohort Profile: The Swedish Longitudinal Occupational Survey of Health (SLOSH).

PMID- 29340638
TI  - Dietary energy, digestible lysine, and available phosphorus levels affect growth
      performance, carcass traits, and amino acid digestibility of broilers.
AB  - A 3-factor, 3-level Box-Behnken design was used to investigate the interaction
      effect of dietary digestible lysine (dLys, 9.5, 10.5, 11.5 g/kg), apparent
      metabolizable energy (AMEn, 12.77, 13.19, 13.61 MJ/kg) and available P (avP, 3.0,
      4.0, 5.0 g/kg) levels on performance and amino acid (AA) digestibility of Ross
      308 male broilers (n = 1,050) from d 14 to 34. The design consisted of 15
      treatments each replicated 5 times with 12 birds per replicate. On d 34, 3 birds
      were sampled from each pen to collect ileal digesta (pooled per pen) to analyze
      AA. Response surface was fitted by first-, second-, or third-degree polynomial
      regressions in JMP statistical software v. 12.0.1. Feed intake (FI), weight gain
      (WG) and feed conversion ratio (FCR) were affected by dLys (linear and quadratic,
      P < 0.01), AMEn (linear, P < 0.01) and AMEn * avP (P < 0.01). Increased dLys
      increased FI but increased AMEn decreased FI in the birds fed the low-avP diet.
      However, when the avP level in the diet was increased, FI decreased to 13 MJ/kg
      AMEn and remained constant thereafter. Increased dLys increased WG whereas an
      increase in AMEn decreased WG in the birds fed the low-avP diet but had no effect
      on WG in those fed the high-avP diet. Increased dLys decreased FCR whereas
      increased AMEn decreased FCR in the birds fed the low-avP diet but had no effect
      on FCR in those fed the high-avP diet. Increased dLys increased breast yield
      percentage (linear, P < 0.01 and quadratic, P < 0.05) whereas increased AMEn
      decreased breast yield percentage (linear, P < 0.01). Dietary levels of dLys or
      avP had positive, linear effects on apparent ileal digestibility (AID) of
      methionine (P < 0.01) and threonine (P < 0.01) but had no effect on other AA (P >
      0.05). These results indicate that increasing dLys levels above current industry
      standard would improve broiler performance irrespective of AMEn or avP levels of
      the diet.

PMID- 29340640
TI  - In Vivo Three-Dimensional Lamina Cribrosa Strains in Healthy, Ocular
      Hypertensive, and Glaucoma Eyes Following Acute Intraocular Pressure Elevation.
AB  - Purpose: To compare in vivo lamina cribrosa (LC) strains (deformations) following
      acute IOP elevation in healthy, glaucoma, and ocular hypertensive subjects.
      Methods: There were 20 healthy, 20 high-tension primary open-angle glaucoma
      (POAG), 16 primary angle-closure glaucoma (PACG), and 20 ocular hypertensive
      (OHT; with normal visual fields) eyes studied. For each test eye, the optic nerve
      head was imaged three times (at baseline IOP, following an acute elevation of IOP
      to approximately 35 then 45 mm Hg using an ophthalmodynamomter) using optical
      coherence tomography (OCT). A three-dimensional (3D) strain-mapping algorithm was
      applied to both sets of baseline and IOP-elevated OCT volumes to extract IOP
      induced 3D strains. Octant-wise LC strains were also extracted to study the
      pattern of local deformation. Results: The average LC strain in OHT subjects
      (3.96%) was significantly lower than that measured in healthy subjects (6.81%; P
      < 0.05). On average, POAG subjects experienced higher strain than the PACG
      subjects (4.05%), healthy subjects experienced higher strains than the POAG and
      PACG subjects, but these difference were not statistically significant. Local LC
      deformations showed lowest strain in the infero-temporal and temporal octant in
      the POAG and OHT subjects. Conclusions: We demonstrate measurable LC strains in
      vivo in humans as a response to acute IOP elevation. In this population, our data
      suggest that OHT LCs experience lower IOP-induced strains than healthy LCs.

PMID- 29340639
TI  - Biomechanical Rigidity and Quantitative Proteomics Analysis of Segmental Regions
      of the Trabecular Meshwork at Physiologic and Elevated Pressures.
AB  - Purpose: The extracellular matrix (ECM) of the trabecular meshwork (TM) modulates
      resistance to aqueous humor outflow, thereby regulating IOP. Glaucoma, a leading
      cause of irreversible blindness worldwide, is associated with changes in the ECM
      of the TM. The elastic modulus of glaucomatous TM is larger than age-matched
      normal TM; however, the biomechanical properties of segmental low (LF) and high
      flow (HF) TM regions and their response to elevated pressure, are unknown.
      Methods: We perfused human anterior segments at two pressures using an ex vivo
      organ culture system. After extraction, we measured the elastic modulus of HF and
      LF TM regions by atomic force microscopy and quantitated protein differences by
      proteomics analyses. Results: The elastic modulus of LF regions was 2.3-fold
      larger than HF regions at physiological (1*) pressure, and 7.4-fold or 3.5-fold
      larger than HF regions at elevated (2*) pressure after 24 or 72 hours,
      respectively. Using quantitative proteomics, comparisons were made between HF and
      LF regions at 1* or 2* pressure. Significant ECM protein differences were
      observed between LF and HF regions perfused at 2*, and between HF regions at 1*
      compared to 2* pressures. Decorin, TGF-beta-induced protein, keratocan, lumican,
      dermatopontin, and thrombospondin 4 were common differential candidates in both
      comparisons. Conclusions: These data show changes in biomechanical properties of
      segmental regions within the TM in response to elevated pressure, and levels of
      specific ECM proteins. Further studies are needed to determine whether these ECM
      proteins are specifically involved in outflow resistance and IOP homeostasis.

PMID- 29340641
TI  - Effects of Age-Related Macular Degeneration on Driving Performance.
AB  - Purpose: To explore differences in driving performance of older adults with age
      related macular degeneration (AMD) and age-matched controls, and to identify the
      visual determinants of driving performance in this population. Methods:
      Participants included 33 older drivers with AMD (mean age [M] = 76.6 +/- 6.1
      years; better eye Age-Related Eye Disease Study grades: early [61%] and
      intermediate [39%]) and 50 age-matched controls (M = 74.6 +/- 5.0 years). Visual
      tests included visual acuity, contrast sensitivity, visual fields, and motion
      sensitivity. On-road driving performance was assessed in a dual-brake vehicle by
      an occupational therapist (masked to drivers' visual status). Outcome measures
      included driving safety ratings (scale of 1-10, where higher values represented
      safer driving), types of driving behavior errors, locations at which errors were
      made, and number of critical errors (CE) requiring an instructor intervention.
      Results: Drivers with AMD were rated as less safe than controls (4.8 vs. 6.2; P =
      0.012); safety ratings were associated with AMD severity (early: 5.5 versus
      intermediate: 3.7), even after adjusting for age. Drivers with AMD had higher CE
      rates than controls (1.42 vs. 0.36, respectively; rate ratio 3.05, 95% confidence
      interval 1.47-6.36, P = 0.003) and exhibited more observation, lane keeping, and
      gap selection errors and made more errors at traffic light-controlled
      intersections (P < 0.05). Only motion sensitivity was significantly associated
      with driving safety in the AMD drivers (P = 0.005). Conclusions: Drivers with
      early and intermediate AMD can exhibit impairments in their driving performance,
      particularly during complex driving situations; motion sensitivity was most
      strongly associated with driving performance. These findings have important
      implications for assessing the driving ability of older drivers with visual
      impairment.

PMID- 29340642
TI  - Identifying Corneal Infections in Formalin-Fixed Specimens Using Next Generation
      Sequencing.
AB  - Purpose: We test the ability of next-generation sequencing, combined with
      computational analysis, to identify a range of organisms causing infectious
      keratitis. Methods: This retrospective study evaluated 16 cases of infectious
      keratitis and four control corneas in formalin-fixed tissues from the pathology
      laboratory. Infectious cases also were analyzed in the microbiology laboratory
      using culture, polymerase chain reaction, and direct staining. Classified
      sequence reads were analyzed with two different metagenomics classification
      engines, Kraken and Centrifuge, and visualized using the Pavian software tool.
      Results: Sequencing generated 20 to 46 million reads per sample. On average, 96%
      of the reads were classified as human, 0.3% corresponded to known vectors or
      contaminant sequences, 1.7% represented microbial sequences, and 2.4% could not
      be classified. The two computational strategies successfully identified the
      fungal, bacterial, and amoebal pathogens in most patients, including all four
      bacterial and mycobacterial cases, five of six fungal cases, three of three
      Acanthamoeba cases, and one of three herpetic keratitis cases. In several cases,
      additional potential pathogens also were identified. In one case with
      cytomegalovirus identified by Kraken and Centrifuge, the virus was confirmed by
      direct testing, while two where Staphylococcus aureus or cytomegalovirus were
      identified by Centrifuge but not Kraken could not be confirmed. Confirmation was
      not attempted for an additional three potential pathogens identified by Kraken
      and 11 identified by Centrifuge. Conclusions: Next generation sequencing combined
      with computational analysis can identify a wide range of pathogens in formalin
      fixed corneal specimens, with potential applications in clinical diagnostics and
      research.

PMID- 29340643
TI  - Association of Low Luminance Questionnaire With Objective Functional Measures in
      Early and Intermediate Age-Related Macular Degeneration.
AB  - Purpose: To determine whether Low Luminance Questionnaire (LLQ) scores are
      associated with objective measures of visual function in early and intermediate
      age-related macular degeneration (AMD). Methods: Cross-sectional study of
      subjects with early AMD Age-Related Eye Disease Study (AREDS) stage 2, N = 33),
      intermediate AMD (AREDS stage 3, N = 47), and age-matched healthy controls (N =
      21). Subjects were interviewed with the LLQ. Psychophysical tests performed
      included best-corrected visual acuity (BCVA), mesopic microperimetry, dark
      adaptometry (DA), low luminance visual acuity (LLVA), and cone contrast test
      (CCT). Low luminance deficit (LLD) was the difference in the number of letters
      read under photopic versus low luminance settings. The relationship between LLQ
      and visual function test scores was assessed with linear regression. Results:
      Subjects with intermediate AMD had significantly lower LLQ composite scores (mean
      = 75.8 +/- 16.7; median = 76, range [29, 97]) compared with early AMD (mean =
      85.3 +/- 13.3; median = 88, range [50, 100], P = 0.007) or controls (mean = 91.4
      +/- 6.5; median = 94, range [79, 99], P < 0.001) in the overall cohort. LLQ
      composite scores were associated with computerized BCVA (beta = 0.516),
      computerized LLVA at two background luminance (1.3 cd/m2, beta = 0.660; 0.5
      cd/m2, beta = 0.489) along with their respective computerized LLDs (beta = -0.531
      and -0.467), rod intercept (beta = -0.312), and CCT green (beta = 0.183) (all P <
      0.05). Only the computerized LLVAs and computerized LLDs remained statistically
      significant after adjusting for AMD versus control status (P < 0.05). Among AMD
      subjects, LLQ composite scores were significantly associated with the
      computerized LLVAs (beta = 0.622 and 0.441) and LLDs (beta = -0.795 and -0.477)
      at both the 1.3 and 0.5 cd/m2 luminance levels, respectively, and these
      associations remained significant after adjusting for AMD severity (P < 0.05).
      Conclusions: Among subjects with early and intermediate AMD, LLQ scores were
      significantly associated with computerized LLVA and LLD. LLQ is a useful patient
      centered functional measure of visual impairment in early and intermediate AMD.

PMID- 29340645
TI  - A Plasma Metabolomic Signature Involving Purine Metabolism in Human Optic Atrophy
      1 (OPA1)-Related Disorders.
AB  - Purpose: Dominant optic atrophy (DOA; MIM [Mendelian Inheritance in Man] 165500),
      resulting in retinal ganglion cell degeneration, is mainly caused by mutations in
      the optic atrophy 1 (OPA1) gene, which encodes a dynamin guanosine triphosphate
      (GTP)ase involved in mitochondrial membrane processing. This work aimed at
      determining whether plasma from OPA1 pathogenic variant carriers displays a
      specific metabolic signature. Methods: We applied a nontargeted clinical
      metabolomics pipeline based on ultra-high-pressure liquid chromatography coupled
      to high-resolution mass spectrometry (UHPLC-HRMS) allowing the exploration of 500
      polar metabolites in plasma. We compared the plasma metabolic profiles of 25
      patients with various OPA1 pathogenic variants and phenotypes to those of 20
      healthy controls. Statistical analyses were performed using univariate and
      multivariate (principal component analysis [PCA], orthogonal partial least
      squares discriminant analysis [OPLS-DA]) methods and a machine learning approach,
      the Biosigner algorithm. Results: A robust and relevant predictive model
      characterizing OPA1 individuals was obtained, based on a complex panel of
      metabolites with altered concentrations. An impairment of the purine metabolism,
      including significant differences in xanthine, hypoxanthine, and inosine
      concentrations, was at the foreground of this signature. In addition, the
      signature was characterized by differences in urocanate, choline, phosphocholine,
      glycerate, 1-oleoyl-rac-glycerol, rac-glycerol-1-myristate, aspartate, glutamate,
      and cystine concentrations. Conclusions: This first metabolic signature reported
      in the plasma of patient carrying OPA1 pathogenic variants highlights the
      unexpected involvement of purine metabolism in the pathophysiology of DOA.

PMID- 29340646
TI  - Visual Fixation Instability in Multiple Sclerosis Measured Using SLO-OCT.
AB  - Purpose: Precise measurements of visual fixation and its instability were
      recorded during optical coherence tomography (OCT) as a marker of neural network
      dysfunction in multiple sclerosis (MS), which could be used to monitor disease
      progression or response to treatment. Methods: A total of 16 MS patients and 26
      normal subjects underwent 30 seconds of scanning laser ophthalmoscope (SLO)-based
      eye tracking during OCT scanning of retinal layer thickness. Study groups
      consisted of normal eyes, MS eyes without prior optic neuritis (MS wo ON), and MS
      eyes with prior optic neuritis (MS + ON). Kernel density estimation quantified
      fixation instability from the distribution of fixation points on the retina. In
      MS wo ON eyes, fixation instability was compared to other measures of visual and
      neurologic function. Results: Fixation instability was increased in MS wo ON eyes
      (0.062 deg2) compared to normal eyes (0.030 deg2, P = 0.015). A further increase
      was seen for MS + ON eyes (0.11 deg2) compared to MS wo ON (P = 0.04) and normal
      (P = 0.006) eyes. Fixation instability correlated weakly with ganglion cell layer
      (GCL) volume and showed no correlation with low-contrast letter acuity, EDSS
      score, or SDMT score. Conclusions: Fixation instability reflects the integrity of
      a widespread neural network germane to visual processing and ocular motor
      control, and is disturbed in MS. Further study of visual fixation, including the
      contribution of microsaccades to fixation instability, may provide insight into
      the localization of fixation abnormalities in MS and introduce innovative and
      easily measured outcomes for monitoring progression and treatment response.

PMID- 29340644
TI  - Proteasome Inhibition Increases the Efficiency of Lentiviral Vector-Mediated
      Transduction of Trabecular Meshwork.
AB  - Purpose: To determine if proteasome inhibition using MG132 increased the
      efficiency of FIV vector-mediated transduction in human trabecular meshwork (TM)
      1 cells and monkey organ-cultured anterior segments (MOCAS). Methods: TM-1 cells
      were pretreated for 1 hour with 0.5% dimethyl sulfoxide (DMSO; vehicle control)
      or 5 to 50 MUM MG132 and transduced with FIV.GFP (green fluorescent protein)- or
      FIV.mCherry-expressing vector at a multiplicity of transduction (MOT) of 20. At
      24 hours, cells were fixed and stained with antibodies for GFP, and positive
      cells were counted, manually or by fluorescence-activated cell sorting (FACS).
      Cells transduced with FIV.GFP particles alone were used as controls. The effect
      of 20 MUM MG132 treatment on high- and low-dose (2 * 107 and 0.8 * 107
      transducing units [TU], respectively) FIV.GFP transduction with or without MG132
      was also evaluated in MOCAS using fluorescence microscopy. Vector genome
      equivalents in cells and tissues were quantified by quantitative (q)PCR on DNA.
      Results: In the MG132 treatment groups, there was a significant dose-dependent
      increase in the percentage of transduced cells at all concentrations tested.
      Vector genome equivalents were also increased in TM-1 cells treated with MG132.
      Increased FIV.GFP expression in the TM was also observed in MOCAS treated with 20
      MUM MG132 and the high dose of vector. Vector genome equivalents were also
      significantly increased in the MOCAS tissues. Increased transduction was not seen
      with the low dose of virus. Conclusions: Proteasome inhibition increased the
      transduction efficiency of FIV particles in TM-1 cells and MOCAS and may be a
      useful adjunct for delivery of therapeutic genes to the TM by lentiviral vectors.

PMID- 29340647
TI  - Fixation Instability: A New Measure of Neurologic Dysfunction in Multiple
      Sclerosis.

PMID- 29340648
TI  - A Novel Strategy for Quantifying Choriocapillaris Flow Voids Using Swept-Source
      OCT Angiography.
AB  - Purpose: To achieve reproducible imaging of the choriocapillaris and associated
      flow voids using swept-source OCT angiography (SS-OCTA). Methods: Subjects were
      enrolled and SS-OCTA was performed using the 3 * 3 mm scan pattern. Blood flow
      was identified using the complex optical microangiography (OMAG) algorithm. The
      choriocapillaris was defined as a slab from the outer boundary of Bruch's
      membrane (BM) to approximately 20 MUm below BM. Compensation for the shadowing
      effect caused by the RPE and BM complex on the choriocapillaris angiogram was
      achieved by using the structural information from the same slab. A thresholding
      method to calculate the percentage of flow voids from a region was developed
      based on a normal database. Results: Twenty normal subjects and 12 subjects with
      drusen were enrolled. SS-OCTA identified the choriocapillaris in normal subjects
      as a lobular plexus of capillaries in the central macula and the lobular
      arrangement became more evident toward the periphery. In all eyes, signal
      compensation resulted in fewer choriocapillaris flow voids with improved
      repeatability of measurements. The best repeatability for the measurement was
      achieved by using 1 standard deviation (SD) for the thresholding strategy.
      Conclusions: SS-OCTA can image the choriocapillaris in vivo, and the
      repeatability of flow void measurements is high in the presence of drusen. The
      ability to image the choriocapillaris and associated flow voids should prove
      useful in understanding disease onset, progression, and response to therapies.

PMID- 29340649
TI  - Optic Nerve Regeneration After Crush Remodels the Injury Site: Molecular Insights
      From Imaging Mass Spectrometry.
AB  - Purpose: Mammalian central nervous system axons fail to regenerate after injury.
      Contributing factors include limited intrinsic growth capacity and an inhibitory
      glial environment. Inflammation-induced optic nerve regeneration (IIR) is thought
      to boost retinal ganglion cell (RGC) intrinsic growth capacity through progrowth
      gene expression, but effects on the inhibitory glial environment of the optic
      nerve are unexplored. To investigate progrowth molecular changes associated with
      reactive gliosis during IIR, we developed an imaging mass spectrometry (IMS)
      based approach that identifies discriminant molecular signals in and around optic
      nerve crush (ONC) sites. Methods: ONC was performed in rats, and IIR was
      established by intravitreal injection of a yeast cell wall preparation. Optic
      nerves were collected at various postcrush intervals, and longitudinal sections
      were analyzed with matrix-assisted laser desorption/ionization (MALDI) IMS and
      data mining. Immunohistochemistry and confocal microscopy were used to compare
      discriminant molecular features with cellular features of reactive gliosis.
      Results: IIR increased the area of the crush site that was occupied by a dense
      cellular infiltrate and mass spectral features consistent with lysosome-specific
      lipids. IIR also increased immunohistochemical labeling for microglia and
      macrophages. IIR enhanced clearance of lipid sulfatide myelin-associated
      inhibitors of axon growth and accumulation of simple GM3 gangliosides in a
      spatial distribution consistent with degradation of plasma membrane from
      degenerated axons. Conclusions: IIR promotes a robust phagocytic response that
      improves clearance of myelin and axon debris. This growth-permissive molecular
      remodeling of the crush injury site extends our current understanding of IIR to
      include mechanisms extrinsic to the RGC.

PMID- 29340650
TI  - Colocalization of Galectin-3 With CD147 Is Associated With Increased
      Gelatinolytic Activity in Ulcerating Human Corneas.
AB  - Purpose: Galectin-3 is a carbohydrate-binding protein known to promote expression
      of matrix metalloproteinases, a hallmark of ulceration, through interaction with
      the extracellular matrix metalloproteinase inducer CD147. The aim of this study
      was to investigate the distribution of galectin-3 in corneas of patients with
      ulcerative keratitis and to determine its relationship to CD147 and the presence
      of gelatinolytic activity. Methods: This was an observational case series
      involving donor tissue from 13 patients with active corneal ulceration and 6
      control corneas. Fixed-frozen sections of the corneas were processed to localize
      galectin-3 and CD147 by immunofluorescence microscopy. Gelatinolytic activity was
      detected by in situ zymography. Results: Tissue from patients with active corneal
      ulceration showed a greater galectin-3 immunoreactivity in basal epithelia and
      stroma compared with controls. Immunofluorescence grading scores revealed
      increased colocalization of galectin-3 and CD147 in corneal ulcers at the
      epithelial-stromal junction and within fibroblasts. Quantitative analysis using
      the Manders' colocalization coefficient demonstrated significant overlap in
      corneas from patients with ulcerative keratitis (M1 = 0.29; M2 = 0.22) as opposed
      to control corneas (M1 = 0.01, P < 0.01; M2 = 0.02, P < 0.05). In these
      experiments, there was a significant positive correlation between the degree of
      galectin-3 and CD147 colocalization and the presence of gelatinolytic activity.
      Conclusions: Our results indicate that concomitant stimulation and colocalization
      of galectin-3 with CD147 are associated with increased gelatinolytic activity in
      the actively ulcerating human cornea and suggest a mechanism by which galectin-3
      may contribute to the degradation of extracellular matrix proteins during
      ulceration.

PMID- 29340651
TI  - Macular Perfusion Parameters in Different Angiocube Sizes: Does The Size Matter
      in Quantitative Optical Coherence Tomography Angiography?
AB  - Purpose: To investigate the macular quantitative parameters interchangeability of
      three different optical coherence tomography angiography (OCT-A) angiocubes
      (i.e., 3 * 3, 6 * 6, and 12 * 12 mm) on healthy subjects and patients affected by
      diabetic retinopathy (DR) and to assess the interrater reliability of such
      indices across the different scan protocols. Methods: Retrospective study
      involving 20 eyes of healthy subjects and 20 eyes with DR. All eyes underwent
      swept-source OCT-A with 3 * 3-, 6 * 6-, and 12 * 12-mm angiocubes centered on the
      fovea. Foveal avascular zone (FAZ) area and vessel density on 3 * 3-, 6 * 6-, and
      12 * 12-mm macular scans were calculated by three independent operators at all
      retina, superficial, deep, and choriocapillary vascular layers.
      Interchangeability and interrater reliabilities were estimated using intraclass
      correlation coefficient (ICC). Results: Interscan reproducibility of FAZ area was
      very strong (ICC > 0.85) at every plexus. On the contrary, vessel density values
      significantly varied across different scan sizes (ICC < 0.51). Intrascan
      interrater reliability was high for all retina and superficial FAZ areas, while
      it was satisfactory at deep capillary plexus only for 3 * 3-mm scan. Conclusions:
      FAZ area at all plexuses is a robust parameter even if calculated on angiocubes
      with different size. However, interrater reliability is higher when measured in
      smaller scans. Conversely, vessel density results depend on the size of
      angiocube, although their interrater reliability is extremely high. Studies
      involving OCT-A should take into consideration that scan size may influence
      macular perfusion parameters and interrater reliability.

PMID- 29340652
TI  - Pain Sensitivity Associated With the Length of the Maximum Interblink Period.
AB  - Purpose: Pain sensitivity has been identified as a factor that affects how
      individuals answer dry eye questionnaires, but it is unknown how it affects
      ocular discomfort. This study used the time that individuals could refrain from
      blinking as an indicator of ocular discomfort and set out to determine whether it
      was related to pain sensitivity, while adjusting for ocular surface conditions.
      Methods: Subjects first completed the Pain Sensitivity Questionnaire to quantify
      pain sensitivity levels. Exposed interpalpebral area, tear meniscus height, tear
      film lipid layer thickness, ocular surface cooling, and noninvasive tear breakup
      were assessed. Subjects were then asked to refrain from blinking until the
      initial onset of discomfort, which was termed "the maximum interblink period"
      (MIBP), while ocular surface cooling rate was simultaneously measured. Subjects
      were seen for four visits over a course of 2 days. Results: Forty-two subjects
      (36 females, 6 males) completed the study, with a mean (SD) age of 23.2 (3.8)
      years. A longer MIBP was associated with decreased pain sensitivity (P = 0.04),
      lower ocular surface cooling rate (P < 0.001), and Asian ethnicity (P = 0.005).
      Based on the results from the mixed-effect model, it is estimated that
      individuals would be able to refrain from blinking for an additional 4 seconds if
      they had the lowest (0.6) compared to the highest (6.1) pain sensitivity in the
      study cohort. Conclusions: The Pain Sensitivity Questionnaire was associated with
      the MIBP length even after adjusting for ocular surface conditions, which
      suggests that pain sensitivity plays a role in influencing how ocular discomfort
      is perceived.

PMID- 29340653
TI  - ATTED-II in 2018: A Plant Coexpression Database Based on Investigation of the
      Statistical Property of the Mutual Rank Index.

PMID- 29340654
TI  - Antioxidant, angiotensin-converting enzyme inhibitory activity and other
      functional properties of egg white proteins and their derived peptides - A
      review.
AB  - Egg white contains many functionally important proteins: ovalbumin (54%),
      ovotransferrin (12%), ovomucoid (11%), ovoglobulin (G2 and G3, 8%), ovomucin
      (3.5%), and lysozyme (3.5%) are major proteins, while ovoinhibitors,
      ovomacroglobulin, ovoglycoprotein, ovoflavoprotein, thiamine-binding proteins,
      and avidin are minor proteins present in egg white. These proteins, as well as
      the peptides derived from the proteins, have been recognized for their functional
      importance as antioxidant, antimicrobial, metal-chelating, anti-viral, anti
      tumour, and angiotensin-converting enzyme (ACE)-inhibitory activities. Among the
      functional properties of the peptides, antioxidant and antimicrobial activities
      are important characteristics for food processing while other properties such as
      ACE-inhibitory activity of the peptides can have important health-related
      functionalities. Bioactive peptides can be produced from egg white proteins by
      enzyme hydrolysis, chemical treatments, or thermal treatments at different pH
      conditions. The effective functional peptides produced from egg white proteins
      are usually smaller than 2 kDa in molecular size. However, these peptides are
      known for their beneficial activities in vitro only, and little work has been
      done to prove their beneficial effects in vivo. Therefore, further studies are
      needed to see if the bioactive peptides derived from egg white proteins are
      helpful for humans in the future.

PMID- 29340655
TI  - Effect of dietary synbiotic supplement on behavioral patterns and growth
      performance of broiler chickens reared under heat stress.
AB  - This study examined the effects of a dietary synbiotic supplement on the
      behavioral patterns and growth performance of broiler chickens exposed to heat
      stress (HS). Three hundred sixty 1-day-old male Ross 708 broiler chicks were
      distributed among 24 floor pens (15 chicks per pen); each pen was randomly
      assigned to one of 3 dietary treatments containing a synbiotic at 0 (control),
      0.5 (0.5X) and 1.0 (1.0X) g/kg. From d 15 to 42, birds were exposed to HS at 32
      degrees C daily from 08:00 to 17:00. Five broiler chickens were randomly marked
      in each pen for behavioral observation. Instantaneous scan sampling was used to
      record the birds' behavioral patterns. Performance parameters were measured on d
      7, 14, 28 and 42. The synbiotic fed birds exhibited more standing, sitting,
      walking, feeding, preening and less wing spreading and panting behaviors (P <
      0.05) compared to birds fed the control diet. The synbiotic group also had higher
      BW, BW gain and feed intake on d 7, 14 and 42 (P < 0.05), and higher BW, feed
      intake and feed conversion ratio at d 28 (P < 0.01). There were no treatment
      effects on drinking behavior, BW gain on d 28 and feed conversion ratio on d 42
      (P > 0.05). There were few dose-related differences of the synbiotic on
      production performance; namely, the 1.0X concentration resulted in the highest BW
      and feed intake on d 14 and 42 (P < 0.05), while BW gain was higher compared to
      the control group only on d 42 (P < 0.05). The results suggest that the synbiotic
      supplement may prove to be an important management tool for the broiler industry
      to diminish the negative effects of HS, potentially safeguarding the welfare and
      production of broiler chickens, particularly in areas that experience hot
      climates.

PMID- 29340656
TI  - Antagonistic effect of Saccharomyces cerevisiae KTP and Issatchenkia occidentalis
      ApC on hyphal development and adhesion of Candida albicans.
AB  - The morphological transition from yeast to a hyphal form, as well as the adhesion
      capability to the gastrointestinal tract, are implicated virulent determinant in
      Candida albicans and could be potential targets for prevention of the
      opportunistic pathogen. Based on this rationale, two yeast strains Saccharomyces
      cerevisiae KTP and Issatchenkia occidentalis ApC along with reference strain
      Saccharomyces boulardii NCDC 363 were screened for the probiotic potential.
      Characters like pH, temperature, bile, simulated gastrointestinal juice tolerance
      tests, and Caco-2 cell line adhesion assay were determined in the present study.
      Further, the evaluation of its impact on C. albicans morphological transition and
      adhesion was assessed using microtitre germ tube test. In terms of probiotic
      characteristics, both the strains were tolerant to pH 2.5 and the presence of
      bile (0.3 to 0.6%) with an optimum growth temperature of 37 degrees C. The strain
      KTP was also resistant to simulated gastric and intestinal juices as compared to
      control (13% and 41%, respectively) and NCDC 363 (55% and 35%, respectively). In
      contrast, both the yeasts had reduced adhesiveness to Caco-2 monolayer. Candida
      virulence in in vitro systems indicated that treatment of live probiotic yeast
      cells (108 ml) effectively reduced the filamentation and adhesion of C. albicans.
      The S. cerevisiae KTP had a profound effect on the hyphal development and
      adhesion when compared to the ApC and NCDC 363. The strain significantly reduced
      (P < .05) the hyphal growth in co-cultivated (93% and 94%, respectively) and pre
      existing hyphae (54% and 68%) of strains C. albicans 183 and 1151. Isolates KTP
      and ApC also reduced the adhesion (~ 22% and 41%, respectively) and transition of
      blastoconidia at two hours of incubation in abiotic surface. This study provides
      knowledge on the effect of potential probiotic yeasts such as Saccharomyces and
      non- Saccharomyces strains against virulence characteristic of Candida albicans.

PMID- 29340657
TI  - Ixodes scapularis (Acari: Ixodidae) Reservoir Host Diversity and Abundance
      Impacts on Dilution of Borrelia burgdorferi (Spirochaetales: Spirochaetaceae) in
      Residential and Woodland Habitats in Connecticut, United States.
AB  - The dilution effect in the zoonotic disease transmission cycle theorizes that an
      increased diversity of host species will alter transmission dynamics, result in a
      decrease in pathogen prevalence, and potentially lower human disease incidence.
      The interrelationship of Borrelia burgdorferi (Johnson, Schmid, Hyde,
      Steigerwalt, and Brenner) (Spirochaetales: Spirochaetaceae), the etiological
      agent of Lyme disease (LD), and its primary vector, blacklegged ticks (Ixodes
      scapularis Say) (Acari: Ixodidae), is a commonly used example of the dilution
      effect, suggesting that an increased diversity of host species will be found in
      large, undisturbed forested tracts and lower diversity in fragmented forests.
      Given that Connecticut woodlands are mature with heavy upper canopies and
      generally poor habitat quality, we hypothesized there would be higher diversity
      of host species resulting in lower prevalence of B. burgdorferi in white-footed
      mice (Peromyscus leucopus Rafinesque) (Rodentia: Cricetidae) in forested
      residential areas. Using camera and live small mammal trapping techniques, we
      determined there was a greater richness of reservoir host species, significantly
      higher encounters with hosts, and significantly lower B. burgdorferi host
      infection in residential areas as compared to large, intact forested stands.
      Furthermore, we determined that the driving factor of pathogen dilution was not
      host species diversity, but rather overall encounter abundance with alternative
      hosts, regardless of habitat type. Our study challenges major concepts of the
      dilution effect within the Connecticut landscape and calls for new managerial
      actions to address the current state of our woodlands and abundance of host
      species in the interest of both forest and public health.

PMID- 29340658
TI  - Cuticle and pore plug properties in the table egg.
AB  - Food safety of table eggs is vital since many pathogens can contaminate the
      unfertilized egg, leading to increased risk of foodborne illness for consumers.
      The eggshell cuticle is the first line of defense to restrict the entry of egg
      associated pathogens, such as Salmonella Enteritidis. The thickness and
      completeness of coverage of the cuticle layer are heritable traits that are
      strongly associated with egg resistance to bacterial penetration. The present
      study characterizes the chemical composition of the eggshell cuticle and
      structure of pore plugs from table eggs. Eggs collected from both brown and white
      egg laying Lohmann flocks (early, mid, and late lay) were either unwashed or
      washed. Pore plugs were characterized using scanning electron microscopy (SEM),
      and elemental composition was determined using energy-dispersive x-ray
      spectroscopy (EDS). SEM observations confirmed that the plug formed by the
      cuticle layer within the eggshell pore remains firmly lodged throughout the
      commercial washing process. The eggshell thickness and cuticle pore length
      visualized in brown eggs was significantly higher than in white eggs in hens of
      all ages. EDS analysis revealed that the pore inner surface was enriched in
      phosphorus and chemically different from the surrounding bulk eggshell mineral.
      Detailed assessment of the cuticle chemical composition was performed by Fourier
      transform infrared spectroscopy (FTIR). Washing of eggs removed cuticle from the
      eggshell surface. There was a trend of lower cuticle coverage with increasing hen
      age for white eggs. A significant reduction in the amount of proteins and
      phosphates and polysaccharides was observed in the cuticle of brown unwashed eggs
      with hen age. In white unwashed eggs, amides and lipids decreased with hen age;
      by contrast, the amount of sulfate was highest at mid-lay. The results from our
      research will assist selective breeding programs that target cuticle integrity
      and pore plug stability to enhance egg resistance to pathogen penetration and
      improve food safety.

PMID- 29340659
TI  - Comparing the Outcomes of Sleeve Gastrectomy and Roux-en-Y Gastric Bypass for
      Severe Obesity.

PMID- 29340660
TI  - Reimagining Obesity in 2018: A JAMA Theme Issue on Obesity.

PMID- 29340661
TI  - Second Cancer Biosimilar Approved.

PMID- 29340662
TI  - Regulatory Pathway for 3D Printing.

PMID- 29340663
TI  - Monthly Buprenorphine Injection Approved for Opioid Use Disorder.

PMID- 29340664
TI  - Long-term Outcomes Following Bariatric Surgery.

PMID- 29340665
TI  - Medical Care Use and Expenditures Associated With Adult Obesity in the United
      States.

PMID- 29340667
TI  - Appropriations for City Health Departments.

PMID- 29340668
TI  - Axillary vs Sentinel Lymph Node Dissection in Women With Invasive Breast Cancer.

PMID- 29340669
TI  - Risks of Statins for Lower-Risk Individuals.

PMID- 29340670
TI  - Trends in Carotid Revascularization Procedures.

PMID- 29340671
TI  - Trends in Carotid Revascularization Procedures.

PMID- 29340672
TI  - Axillary vs Sentinel Lymph Node Dissection in Women With Invasive Breast Cancer
      Reply.

PMID- 29340673
TI  - Risks of Statins for Lower-Risk Individuals-Reply.

PMID- 29340674
TI  - Trends in Carotid Revascularization Procedures-Reply.

PMID- 29340675
TI  - Interest in the Ketogenic Diet Grows for Weight Loss and Type 2 Diabetes.

PMID- 29340676
TI  - Effect of Laparoscopic Sleeve Gastrectomy vs Laparoscopic Roux-en-Y Gastric
      Bypass on Weight Loss at 5 Years Among Patients With Morbid Obesity: The
      SLEEVEPASS Randomized Clinical Trial.
AB  - Importance: Laparoscopic sleeve gastrectomy for treatment of morbid obesity has
      increased substantially despite the lack of long-term results compared with
      laparoscopic Roux-en-Y gastric bypass. Objective: To determine whether
      laparoscopic sleeve gastrectomy and laparoscopic Roux-en-Y gastric bypass are
      equivalent for weight loss at 5 years in patients with morbid obesity. Design,
      Setting, and Participants: The Sleeve vs Bypass (SLEEVEPASS) multicenter,
      multisurgeon, open-label, randomized clinical equivalence trial was conducted
      from March 2008 until June 2010 in Finland. The trial enrolled 240 morbidly obese
      patients aged 18 to 60 years, who were randomly assigned to sleeve gastrectomy or
      gastric bypass with a 5-year follow-up period (last follow-up, October 14, 2015).
      Interventions: Laparoscopic sleeve gastrectomy (n = 121) or laparoscopic Roux-en
      Y gastric bypass (n = 119). Main Outcomes and Measures: The primary end point was
      weight loss evaluated by percentage excess weight loss. Prespecified equivalence
      margins for the clinical significance of weight loss differences between gastric
      bypass and sleeve gastrectomy were -9% to +9% excess weight loss. Secondary end
      points included resolution of comorbidities, improvement of quality of life
      (QOL), all adverse events (overall morbidity), and mortality. Results: Among 240
      patients randomized (mean age, 48 [SD, 9] years; mean baseline body mass index,
      45.9, [SD, 6.0]; 69.6% women), 80.4% completed the 5-year follow-up. At baseline,
      42.1% had type 2 diabetes, 34.6% dyslipidemia, and 70.8% hypertension. The
      estimated mean percentage excess weight loss at 5 years was 49% (95% CI, 45%-52%)
      after sleeve gastrectomy and 57% (95% CI, 53%-61%) after gastric bypass
      (difference, 8.2 percentage units [95% CI, 3.2%-13.2%], higher in the gastric
      bypass group) and did not meet criteria for equivalence. Complete or partial
      remission of type 2 diabetes was seen in 37% (n = 15/41) after sleeve gastrectomy
      and in 45% (n = 18/40) after gastric bypass (P > .99). Medication for
      dyslipidemia was discontinued in 47% (n = 14/30) after sleeve gastrectomy and 60%
      (n = 24/40) after gastric bypass (P = .15) and for hypertension in 29% (n =
      20/68) and 51% (n = 37/73) (P = .02), respectively. There was no statistically
      significant difference in QOL between groups (P = .85) and no treatment-related
      mortality. At 5 years the overall morbidity rate was 19% (n = 23) for sleeve
      gastrectomy and 26% (n = 31) for gastric bypass (P = .19). Conclusions and
      Relevance: Among patients with morbid obesity, use of laparoscopic sleeve
      gastrectomy compared with use of laparoscopic Roux-en-Y gastric bypass did not
      meet criteria for equivalence in terms of percentage excess weight loss at 5
      years. Although gastric bypass compared with sleeve gastrectomy was associated
      with greater percentage excess weight loss at 5 years, the difference was not
      statistically significant, based on the prespecified equivalence margins. Trial
      Registration: clinicaltrials.gov Identifier: NCT00793143.

PMID- 29340677
TI  - Association of Bariatric Surgery Using Laparoscopic Banding, Roux-en-Y Gastric
      Bypass, or Laparoscopic Sleeve Gastrectomy vs Usual Care Obesity Management With
      All-Cause Mortality.
AB  - Importance: Bariatric surgery is an effective and safe approach for weight loss
      and short-term improvement in metabolic disorders such as diabetes. However,
      studies have been limited in most settings by lack of a nonsurgical group, losses
      to follow-up, missing data, and small sample sizes in clinical trials and
      observational studies. Objective: To assess the association of 3 common types of
      bariatric surgery compared with nonsurgical treatment with mortality and other
      clinical outcomes among obese patients. Design, Setting, and Participants:
      Retrospective cohort study in a large Israeli integrated health fund covering 54%
      of Israeli citizens with less than 1% turnover of members annually. Obese adult
      patients who underwent bariatric surgery between January 1, 2005, and December
      31, 2014, were selected and compared with obese nonsurgical patients matched on
      age, sex, body mass index (BMI), and diabetes, with a final follow-up date of
      December 31, 2015. A total of 33 540 patients were included in this study.
      Exposures: Bariatric surgery (laparoscopic banding, Roux-en-Y gastric bypass, or
      laparoscopic sleeve gastrectomy) or usual care obesity management only (provided
      by a primary care physician and which may include dietary counseling and behavior
      modification). Main Outcomes and Measures: The primary outcome, all-cause
      mortality, matched and adjusted for BMI prior to surgery, age, sex, socioeconomic
      status, diabetes, hyperlipidemia, hypertension, cardiovascular disease, and
      smoking. Results: The study population included 8385 patients who underwent
      bariatric surgery (median age, 46 [IQR, 37-54] years; 5490 [65.5%] women;
      baseline median BMI, 40.6 [IQR, 38.5-43.7]; laparoscopic banding [n = 3635],
      gastric bypass [n = 1388], laparoscopic sleeve gastrectomy [n = 3362], and 25 155
      nonsurgical matched patients (median age, 46 [IQR, 37-54] years; 16 470 [65.5%]
      women; baseline median BMI, 40.5 [IQR, 37.0-43.5]). The availability of follow-up
      data was 100% for all-cause mortality. There were 105 deaths (1.3%) among
      surgical patients during a median follow-up of 4.3 (IQR, 2.8-6.6) years
      (including 61 [1.7%] who underwent laparoscopic banding, 18 [1.3%] gastric
      bypass, and 26 [0.8%] sleeve gastrectomy), and 583 deaths (2.3%) among
      nonsurgical patients during a median follow-up of 4.0 (IQR, 2.6-6.2) years. The
      absolute difference was 2.51 (95% CI, 1.86-3.15) fewer deaths/1000 person-years
      in the surgical vs nonsurgical group. Adjusted hazard ratios (HRs) for mortality
      among nonsurgical vs surgical patients were 2.02 (95% CI, 1.63-2.52) for the
      entire study population; by surgical type, HRs were 2.01 (95% CI, 1.50-2.69) for
      laparoscopic banding, 2.65 (95% CI, 1.55-4.52) for gastric bypass, and 1.60 (95%
      CI, 1.02-2.51) for laparoscopic sleeve gastrectomy. Conclusions and Relevance:
      Among obese patients in a large integrated health fund in Israel, bariatric
      surgery using laparoscopic banding, gastric bypass, or laparoscopic sleeve
      gastrectomy, compared with usual care nonsurgical obesity management, was
      associated with lower all-cause mortality over a median follow-up of
      approximately 4.5 years. The evidence of this association adds to the limited
      literature describing beneficial outcomes of these 3 types of bariatric surgery
      compared with usual care obesity management alone.

PMID- 29340678
TI  - Lifestyle Intervention and Medical Management With vs Without Roux-en-Y Gastric
      Bypass and Control of Hemoglobin A1c, LDL Cholesterol, and Systolic Blood
      Pressure at 5 Years in the Diabetes Surgery Study.
AB  - Importance: The Roux-en-Y gastric bypass is effective in achieving established
      diabetes treatment targets, but durability is unknown. Objective: To compare
      durability of Roux-en-Y gastric bypass added to intensive lifestyle and medical
      management in achieving diabetes control targets. Design, Setting, and
      Participants: Observational follow-up of a randomized clinical trial at 4 sites
      in the United States and Taiwan, involving 120 participants who had a hemoglobin
      A1c (HbA1c) level of 8.0% or higher and a body mass index between 30.0 and 39.9
      (enrolled between April 2008 and December 2011) were followed up for 5 years,
      ending in November 2016. Interventions: Lifestyle-intensive medical management
      intervention based on the Diabetes Prevention Program and LookAHEAD trials for 2
      years, with and without (60 participants each) Roux-en-Y gastric bypass surgery
      followed by observation to year 5. Main Outcomes and Measures: The American
      Diabetes Association composite triple end point of hemoglobin A1c less than 7.0%,
      low-density lipoprotein cholesterol less than 100 mg/dL, and systolic blood
      pressure less than 130 mm Hg at 5 years. Results: Of 120 participants who were
      initially randomized (mean age, 49 years [SD, 8 years], 72 women [60%]), 98 (82%)
      completed 5 years of follow-up. Baseline characteristics were similar between
      groups: mean (SD) body mass index 34.4 (3.2) for the lifestyle-medical management
      group and 34.9 (3.0) for the gastric bypass group and had hemoglobin A1c levels
      of 9.6% (1.2) and 9.6% (1.0), respectively. At 5 years, 13 participants (23%) in
      the gastric bypass group and 2 (4%) in the lifestyle-intensive medical management
      group had achieved the composite triple end point (difference, 19%; 95% CI, 4%
      34%; P = .01). In the fifth year, 31 patients (55%) in the gastric bypass group
      vs 8 (14%) in the lifestyle-medical management group achieved an HbA1c level of
      less than 7.0% (difference, 41%; 95% CI, 19%-63%; P = .002). Gastric bypass had
      more serious adverse events than did the lifestyle-medical management
      intervention, 66 events vs 38 events, most frequently gastrointestinal events and
      surgical complications such as strictures, small bowel obstructions, and leaks.
      Gastric bypass had more parathyroid hormone elevation but no difference in B12
      deficiency. Conclusions and Relevance: In extended follow-up of obese adults with
      type 2 diabetes randomized to adding gastric bypass compared with lifestyle and
      intensive medical management alone, there remained a significantly better
      composite triple end point in the surgical group at 5 years. However, because the
      effect size diminished over 5 years, further follow-up is needed to understand
      the durability of the improvement. Trial Registration: clinicaltrials.gov
      Identifier: NCT00641251.

PMID- 29340679
TI  - Effect of Laparoscopic Sleeve Gastrectomy vs Laparoscopic Roux-en-Y Gastric
      Bypass on Weight Loss in Patients With Morbid Obesity: The SM-BOSS Randomized
      Clinical Trial.
AB  - Importance: Sleeve gastrectomy is increasingly used in the treatment of morbid
      obesity, but its long-term outcome vs the standard Roux-en-Y gastric bypass
      procedure is unknown. Objective: To determine whether there are differences
      between sleeve gastrectomy and Roux-en-Y gastric bypass in terms of weight loss,
      changes in comorbidities, increase in quality of life, and adverse events.
      Design, Setting, and Participants: The Swiss Multicenter Bypass or Sleeve Study
      (SM-BOSS), a 2-group randomized trial, was conducted from January 2007 until
      November 2011 (last follow-up in March 2017). Of 3971 morbidly obese patients
      evaluated for bariatric surgery at 4 Swiss bariatric centers, 217 patients were
      enrolled and randomly assigned to sleeve gastrectomy or Roux-en-Y gastric bypass
      with a 5-year follow-up period. Interventions: Patients were randomly assigned to
      undergo laparoscopic sleeve gastrectomy (n = 107) or laparoscopic Roux-en-Y
      gastric bypass (n = 110). Main Outcomes and Measures: The primary end point was
      weight loss, expressed as percentage excess body mass index (BMI) loss.
      Exploratory end points were changes in comorbidities and adverse events. Results:
      Among the 217 patients (mean age, 45.5 years; 72% women; mean BMI, 43.9) 205
      (94.5%) completed the trial. Excess BMI loss was not significantly different at 5
      years: for sleeve gastrectomy, 61.1%, vs Roux-en-Y gastric bypass, 68.3%
      (absolute difference, -7.18%; 95% CI, -14.30% to -0.06%; P = .22 after adjustment
      for multiple comparisons). Gastric reflux remission was observed more frequently
      after Roux-en-Y gastric bypass (60.4%) than after sleeve gastrectomy (25.0%).
      Gastric reflux worsened (more symptoms or increase in therapy) more often after
      sleeve gastrectomy (31.8%) than after Roux-en-Y gastric bypass (6.3%). The number
      of patients with reoperations or interventions was 16/101 (15.8%) after sleeve
      gastrectomy and 23/104 (22.1%) after Roux-en-Y gastric bypass. Conclusions and
      Relevance: Among patients with morbid obesity, there was no significant
      difference in excess BMI loss between laparoscopic sleeve gastrectomy and
      laparoscopic Roux-en-Y gastric bypass at 5 years of follow-up after surgery.
      Trial Registration: clinicaltrials.gov Identifier: NCT00356213.

PMID- 29340681
TI  - Sleeve Gastrectomy for Weight Loss.

PMID- 29340680
TI  - Association of Bariatric Surgery vs Medical Obesity Treatment With Long-term
      Medical Complications and Obesity-Related Comorbidities.
AB  - Importance: The association of bariatric surgery and specialized medical obesity
      treatment with beneficial and detrimental outcomes remains uncertain. Objective:
      To compare changes in obesity-related comorbidities in patients with severe
      obesity (body mass index >=40 or >=35 and at least 1 comorbidity) undergoing
      bariatric surgery or specialized medical treatment. Design, Setting, and
      Participants: Cohort study with baseline data of exposures from November 2005
      through July 2010 and follow-up data from 2006 until death or through December
      2015 at a tertiary care outpatient center, Vestfold Hospital Trust, Norway.
      Consecutive treatment-seeking adult patients (n = 2109) with severe obesity
      assessed (221 patients excluded and 1888 patients included). Exposures: Bariatric
      surgery (n = 932, 92% gastric bypass) or specialized medical treatment (n = 956)
      including individual or group-based lifestyle intervention programs. Main
      Outcomes and Measures: Primary outcomes included remission and new onset of
      hypertension based on drugs dispensed according to the Norwegian Prescription
      Database. Prespecified secondary outcomes included changes in comorbidities.
      Adverse events included complications retrieved from the Norwegian Patient
      Registry and a local laboratory database. Results: Among 1888 patients included
      in the study, the mean (SD) age was 43.5 (12.3) years (1249 women [66%]; mean
      [SD] baseline BMI, 44.2 [6.1]; 100% completed follow-up at a median of 6.5 years
      [range, 0.2-10.1]). Surgically treated patients had a greater likelihood of
      remission and lesser likelihood for new onset of hypertension (remission:
      absolute risk [AR], 31.9% vs 12.4%); risk difference [RD], 19.5% [95% CI, 15.8%
      23.2%], relative risk [RR], 2.1 [95% CI, 2.0-2.2]; new onset: AR, 3.5% vs 12.2%,
      RD, 8.7% [95% CI, 6.7%-10.7%], RR, 0.4 [95% CI, 0.3-0.5]; greater likelihood of
      diabetes remission: AR, 57.5% vs 14.8%; RD, 42.7% [95% CI, 35.8%-49.7%], RR, 3.9
      [95% CI, 2.8-5.4]; greater risk of new-onset depression: AR, 8.9% vs 6.5%; RD,
      2.4% [95% CI, 1.3%-3.5%], RR, 1.5 [95% CI, 1.4-1.7]; and treatment with opioids:
      AR, 19.4% vs 15.8%, RD, 3.6% [95% CI, 2.3%-4.9%], RR, 1.3 [95% CI, 1.2-1.4]).
      Surgical patients had a greater risk for undergoing at least 1 additional
      gastrointestinal surgical procedure (AR, 31.3% vs 15.5%; RD, 15.8% [95% CI, 13.1%
      18.5%]; RR, 2.0 [95% CI, 1.7-2.4]). The proportion of patients with low ferritin
      levels was significantly greater in the surgical group (26% vs 12%, P < .001).
      Conclusions and Relevance: Among patients with severe obesity followed up for a
      median of 6.5 years, bariatric surgery compared with medical treatment was
      associated with a clinically important increased risk for complications, as well
      as lower risks of obesity-related comorbidities. The risk for complications
      should be considered in the decision-making process.

PMID- 29340684
TI  - Evolving Societal Norms of Obesity: What Is the Appropriate Response?

PMID- 29340685
TI  - Can the Government Require Health Warnings on Sugar-Sweetened Beverage
      Advertisements?

PMID- 29340686
TI  - Taxes and Sugar-Sweetened Beverages.

PMID- 29340687
TI  - Toward Precision Approaches for the Prevention and Treatment of Obesity.

PMID- 29340688
TI  - Counting Calories as an Approach to Achieve Weight Control.

PMID- 29340689
TI  - Fitness or Fatness: Which Is More Important?

PMID- 29340690
TI  - Possible Biomarkers of Deadly Ebola.

PMID- 29340691
TI  - Dangers of Substandard or Falsified Medicines.

PMID- 29340692
TI  - Combination Strategy Associated With Reduced HIV Incidence in Uganda.

PMID- 29340693
TI  - Can granulomatosis with polyangiitis be diagnosed earlier in primary care? A case
      control study.
AB  - Background: People with granulomatosis with polyangiitis (GPA) commonly described
      long delays before diagnosis. Aim: To study the natural history of GPA prior to
      diagnosis using primary care data, and determine whether clinical features could
      be identified to help earlier diagnosis. Design: Case-control study using the
      Clinical Practice Research Datalink. Methods: We compared primary care activity
      and clinical features between cases and 10 matched controls. Results: We
      identified 757 cases and matched 7546 controls. Compared to controls, cases had
      more GP consultations and overall healthcare activity in the 5 years prior to
      their diagnosis, with a marked increase in the year before diagnosis, and
      particularly in the last 3 months. However, consultations were mostly for
      symptoms that were not specifically related to GPA. In the year prior to
      diagnosis, the most frequent and strongly predictive clinical features of GPA
      were Ear Nose and Throat (ENT) symptoms [34.5% of cases, odds ratio (OR) 10.5,
      95% confidence intervals (CI) 8.6-12.7], and general (constitutional) symptoms
      (21.5% of cases, OR 9.0, 95% CI 7.1-11.3). In the year before diagnosis a larger
      number of cases attended secondary care (382, 50.5%) than had records of clinical
      features of GPA. Conclusions: After discussing our findings, we conclude that it
      would be difficult to identify cases of GPA earlier in primary care. Our results
      support a need for heightened awareness of this condition among secondary care
      clinicians, especially those assessing emergency admissions, and in the clinics
      which were most frequently attended by cases 3-12 months prior to diagnosis.

PMID- 29340694
TI  - Death row prisoners-regret for the past and fear for the future?

PMID- 29340696
TI  - From Southeast Asia to the Sewers: Study Determines New Geographic Origins of
      Brown Rats.

PMID- 29340695
TI  - Development and psychometric properties of the Hookah Smoking Initiation for
      Women Questionnaire (HIWQ).
AB  - The aims of this study were to design the Hookah Smoking Initiation for Women
      Questionnaire (HIWQ) and determine its psychometric properties. This was a
      sequential exploratory mixed-methods design consisting of qualitative and
      quantitative phases. This study was conducted from August 2012 to July 2013 in
      Tehran. In the qualitative phase, semi-structured interviews were held with 36
      Iranian women for developing a preliminary item pool. Consequently, during the
      quantitative phase, the psychometric properties of the questionnaire were
      determined with the collaboration of 323 women living in various geographical
      locations in Tehran, Iran. Content validity of the questionnaire was examined by
      a panel of experts. The questionnaire's construct validity was assessed using
      exploratory factor analysis and confirmatory factor analyses. The Cronbach's
      alpha coefficient was calculated to check the questionnaire's internal
      consistency reliability. Moreover, its stability was tested using the test-retest
      method. Exploratory factor analysis indicated that the HIQW could best be
      explained by a six-factor solution: 'drawing the attention of other people', the
      need to having fun and being relaxed, 'hookah smoking in the family',
      'availability of hookah', 'curiosity' and 'having a positive attitude toward
      hookah'. It also was found that the construct and content validity, and the
      reliability of the questionnaire were satisfactory (alpha = 0.83, ICC = 0.94).
      The HIQW was valid and reliable. Therefore, healthcare professionals can use it
      for evaluating the hookah smoking initiation in women. Future studies are
      required to refine this questionnaire and assess its applicability in different
      cultures and contexts.

PMID- 29340697
TI  - Genetic and clinical evidence of mitochondrial dysfunction in autism spectrum
      disorder and intellectual disability.
AB  - Clinical conditions commonly associated with mitochondrial disorders (CAMDs) are
      often present in autism spectrum disorders (ASD) and intellectual disability
      (ID). Therefore, the mitochondrial dysfunction hypothesis has been proposed as a
      transversal mechanism that may function in both disorders. Here, we investigated
      the presence of conditions associated with mitochondrial disorders and
      mitochondrial DNA (mtDNA) alterations in 122 subjects who presented ASD with ID
      (ASD group), 115 subjects who presented ID but not ASD (ID group) and 112 healthy
      controls (HC group). We assessed in the three study groups the presence of the
      clinical conditions through a questionnaire and the mtDNA content of two
      mitochondrial genes, MT-ND1 and MT-ND4, by qPCR. The mtDNA sequences of 98 ASD
      and 95 ID subjects were obtained by mtDNA-targeted next generation sequencing and
      analysed through the MToolBox pipeline to identify mtDNA mutations. Subjects with
      ASD and ID showed higher frequencies of constipation, edema, seizures, vision
      alterations, strabismus and sphincter incontinence than HCs subjects. ASD and ID
      subjects showed significantly lower mtDNA content than HCs in both MT-ND1 and MT
      ND4 genes. In addition, we identified 49 putative pathogenic variants with a
      heteroplasmy level higher than 60%: 8 missense, 29 rRNA and 12 tRNA variants. A
      total of 28.6% of ASD and 30.5% of ID subjects carried at least one putative
      pathogenic mtDNA mutation. The high frequency of CAMDs, the low mtDNA content and
      the presence of putative pathogenic mtDNA mutations observed in both ASD and ID
      subjects are evidence of mitochondrial dysfunction in ASD and ID.

PMID- 29340698
TI  - Simultaneous detection of chicken cytokines in plasma samples using the Bio-Plex
      assay.
AB  - A chicken multiplex cytokine assay (Bio-Plex) to detect four different cytokines
      (IL-2, IL-12, IL-10, and interferon gamma) simultaneously in plasma samples was
      designed. Most standard curves range between 1 to 5 pg/mL and 5,000 pg/mL, except
      for IFNgamma with the range of 50 to 25,000 pg/mL. Such a chicken multiplex assay
      proved to be fast and reliable, and comparable in sensitivity, accuracy, and
      reproducibility to conventional enzyme-linked immunosorbent assays. Comparison of
      the multiplex assay with the ELISA technique using the same clones of detection
      and capture antibodies resulted in correlation coefficients for all cytokines
      ranging from 0.95 to 0.99. Lower limit of detection and limit of quantification
      values were obtained for all tested cytokines by the Bio-Plex assay compared with
      ELISA. To reduce the risk of cross-reaction with other proteins, the Bio-Plex
      system was used, combining the principle of sandwich immunoassay with the Luminex
      bead-based technology. The cytokine standard recoveries for each cytokine varied
      between 86 and 118% in dynamic concentration ranges. A chicken multiplex cytokine
      assay (Bio-Plex) provided a more complete picture of differences between the
      Th1/Th2 cytokine profiles of the immunized via a new system of antigen delivery
      into chicken antigen-presenting cells and control groups. This multiplexed
      fluorescent-bead-based detection assay can be used as a quantitative or
      comparative tool for the study of the chicken ex vivo cellular immune response.

PMID- 29340700
TI  - Finding Their Inner Bird: Using Modern Genomics to Turn Alligator Scales into
      Birdlike Feathers.

PMID- 29340699
TI  - Long-term expression of glomerular genes in diabetic nephropathy.
AB  - Background: Although diabetic nephropathy (DN) is the most common cause for end
      stage renal disease in western societies, its pathogenesis still remains largely
      unclear. A different gene pattern of diabetic and healthy kidney cells is one of
      the probable explanations. Numerous signalling pathways have emerged as important
      pathophysiological mechanisms for diabetes-induced renal injury. Methods:
      Glomerular cells, as podocytes or mesangial cells, are predominantly involved in
      the development of diabetic renal lesions. While many gene assays concerning DN
      are performed with whole kidney or renal cortex tissue, we isolated glomeruli
      from black and tan, brachyuric (BTBR) obese/obese (ob/ob) and wildtype mice at
      four different timepoints (4, 8, 16 and 24 weeks) and performed an mRNA
      microarray to identify differentially expressed genes (DEGs). In contrast to many
      other diabetic mouse models, these homozygous ob/ob leptin-deficient mice develop
      not only a severe type 2 diabetes, but also diabetic kidney injury with all the
      clinical and especially histologic features defining human DN. By functional
      enrichment analysis we were able to investigate biological processes and pathways
      enriched by the DEGs at different disease stages. Altered expression of nine
      randomly selected genes was confirmed by quantitative polymerase chain reaction
      from glomerular RNA. Results: Ob/ob type 2 diabetic mice showed up- and
      downregulation of genes primarily involved in metabolic processes and pathways,
      including glucose, lipid, fatty acid, retinol and amino acid metabolism. Members
      of the CYP4A and ApoB family were found among the top abundant genes. But more
      interestingly, altered gene loci showed enrichment for processes and pathways
      linked to angioneogenesis, complement cascades, semaphorin pathways, oxidation
      and reduction processes and renin secretion. Conclusion: The gene profile of BTBR
      ob/ob type 2 diabetic mice we conducted in this study can help to identify new
      key players in molecular pathogenesis of diabetic kidney injury.

PMID- 29340701
TI  - Impact of graft loss among kidney diseases with a high risk of post-transplant
      recurrence in the paediatric population.

PMID- 29340702
TI  - Risk and Protective Factors for Depressive Symptoms Among African American Men:
      An Application of the Stress Process Model.
AB  - Objectives: This study employs the stress process model (SPM) to identify
      risk/protective factors for mental health among adult African American men.
      Method: Using a community-based sample of Miami, FL residents linked to
      neighborhood Census data, this study identifies risk/protective factors for
      depressive symptomatology using a sample of 248 adult African American men.
      Results: The stress process variables independently associated with depressive
      symptoms were family support, mastery, self-esteem, chronic stressors, and daily
      discrimination. While mastery and self-esteem mediated the relationship between
      neighborhood income and depressive symptoms, perceived family support served as a
      buffer for stress exposure. Collectively, the SPM explains nearly half of the
      variability in depressive symptoms among African American men. Discussion: The
      SPM is a useful conceptual framework for identifying psychosocial risk/protective
      factors and directing health initiatives and policies aimed at improving the
      psychological health of African American men.

PMID- 29340703
TI  - Psychosocial Influences of African Americans Men's Health.

PMID- 29340704
TI  - Delayed conception in women with low-urinary iodine concentrations: a population
      based prospective cohort study.
AB  - STUDY QUESTION: Is iodine deficiency associated with decreased fecundability?
      SUMMARY ANSWER: Moderate to severe iodine deficiency is associated with a 46%
      decrease in fecundability. WHAT IS KNOWN ALREADY: Iodine deficiency is common in
      women of childbearing age but its effect on fecundability has not been
      investigated. STUDY DESIGN, SIZE, DURATION: The LIFE Study, a population-based
      prospective cohort study, enrolled 501 women who had discontinued contraception
      within 2 months to become pregnant between 2005 and 2009. PARTICIPANTS/MATERIALS,
      SETTING, METHODS: Women reported on risk factors for infertility by interview
      then kept daily journals of relevant information. Women used fertility monitors
      to time intercourse relative to ovulation then used home digital pregnancy tests
      to identify pregnancies on the day of expected menstruation. Urine samples for
      iodine analysis were collected on enrollment. MAIN RESULTS AND THE ROLE OF
      CHANCE: Samples were in the deficiency range in 44.3% of participants. The group
      whose iodine-creatinine ratios were below 50 MUg/g (moderate to severe
      deficiency) had a 46% reduction in fecundity (P = 0.028) compared with the group
      whose iodine-creatinine ratios were in the adequate range: adjusted fecundability
      odds ratio of becoming pregnant per cycle, 0.54 (95% confidence interval 0.31
      0.94). LIMITATIONS, REASONS FOR CAUTION: Iodine concentrations vary within
      individuals over time, so the data must be interpreted by group as we have done;
      residual confounding is possible. WIDER IMPLICATIONS OF THE FINDINGS: Significant
      delays in becoming pregnant occur at iodine concentrations that are common in
      women in the USA and parts of Europe. Replicating these findings will be
      important to determine whether improving iodine status could be beneficial in
      improving fecundability. STUDY FUNDING/COMPETING INTEREST(S): This study was
      funded by the Intramural Research Program, Eunice Kennedy Shriver National
      Institute of Child Health and Human Development, National Institutes of Health,
      USA. Contracts N01-HD-3-3355; N01-HD-3-3356; N01-HD-3-3358 and
      HHSN275201100001l/HHSN27500007. None of the authors has any conflict of interest
      to declare.

PMID- 29340705
TI  - Author Correction: Ouabain attenuates ovalbumin-induced airway inflammation.
AB  - In the original publication, author missed to include the financial support from
      CAPES/PROCAD-2013. The complete funding text should read as follows.

PMID- 29340706
TI  - Prognostic implications of the co-detection of the urokinase plasminogen
      activator system and osteopontin in patients with non-small-cell lung cancer
      undergoing radiotherapy and correlation with gross tumor volume.
AB  - BACKGROUND: The urokinase plasminogen activator system (uPA, uPAR, PAI-1) is
      upregulated in cancer and high plasma levels are associated with poor prognosis.
      Their interaction with hypoxia-related osteopontin (OPN) which is also
      overexpressed in malignant tumors suggests potential clinical relevance. However,
      the prognostic role of the uPA system in the radiotherapy (RT) of non-small-cell
      lung cancer (NSCLC), particularly in combination with OPN, has not been
      investigated so far. METHODS: uPA, uPAR, PAI-1 and OPN plasma levels of 81
      patients with locally advanced or metastasized NSCLC were prospectively analyzed
      by ELISA before RT and were correlated to clinical patient/tumor data and
      prognosis after RT. RESULTS: uPAR plasma levels were higher in M1; uPA and PAI-1
      levels were higher in M0 NSCLC patients. uPAR correlated with uPA (p < 0.001)
      which also correlated with PAI-1 (p < 0.001). The prognostic impact of OPN plasma
      levels in the RT of NSCLC was previously reported by our group. PAI-I plasma
      levels significantly impacted overall (OS) and progression-free survival (PFS).
      Low PAI-1 levels were associated with a significantly reduced OS and PFS with a
      nearly 2-fold increased risk of death (p = 0.029) and tumor progression (p =
      0.029). In multivariate analysis, PAI-1 levels remained an independent prognostic
      factor for OS and PFS with a 3-fold increased risk of death (p = 0.001). If PAI-1
      plasma levels were combined with OPN or tumor volume, we found an additive
      prognostic impact on OS and PFS with a 2.5- to 3-fold increased risk of death (p
      = 0.01). CONCLUSION: Our results suggest that PAI-1 but not uPA and uPAR might
      add prognostic information in patients with advanced NSCLC undergoing RT. High
      pretreatment PAI-1 plasma levels were found predominantly in M0-stage patients
      and indicate a favorable prognosis as opposed to OPN where high plasma levels are
      associated with poor survival and metastasis. In combination, PAI-1 and OPN
      levels successfully predicted outcome and additively correlated with prognosis.
      These findings support the notion of an antidromic prognostic impact of OPN and
      PAI-1 plasma levels in the RT of advanced NSCLC.

PMID- 29340707
TI  - VRK1 and AURKB form a complex that cross inhibit their kinase activity and the
      phosphorylation of histone H3 in the progression of mitosis.
AB  - Regulation of cell division requires the integration of signals implicated in
      chromatin reorganization and coordination of its sequential changes in mitosis.
      Vaccinia-related kinase 1 (VRK1) and Aurora B (AURKB) are two nuclear kinases
      involved in different steps of cell division. We have studied whether there is
      any functional connection between these two nuclear kinases, which phosphorylate
      histone H3 in Thr3 and Ser10, respectively. VRK1 and AURKB are able to form a
      stable protein complex, which represents only a minor subpopulation of each
      kinase within the cell and is detected following nocodazole release. Each kinase
      is able to inhibit the kinase activity of the other kinase, as well as inhibit
      their specific phosphorylation of histone H3. In locations where the two kinases
      interact, there is a different pattern of histone modifications, indicating that
      there is a local difference in chromatin during mitosis because of the local
      complexes formed by these kinases and their asymmetric intracellular
      distribution. Depletion of VRK1 downregulates the gene expression of BIRC5
      (survivin) that recognizes H3-T3ph, both are dependent on the activity of VRK1,
      and is recovered with kinase active murine VRK1, but not with a kinase-dead
      protein. The H3-Thr3ph-survivin complex is required for AURB recruitment, and
      their loss prevents the localization of ACA and AURKB in centromeres. The cross
      inhibition of the kinases at the end of mitosis might facilitate the formation of
      daughter cells. A sequential role for VRK1, AURKB, and haspin in the progression
      of mitosis is proposed.

PMID- 29340709
TI  - [Lichen sclerosus : Symptoms, diagnosis, therapeutic procedures].
AB  - Lichen sclerosus is a chronic, inflammatory dermatosis that usually affects the
      anogenital area. Early diagnosis and subsequent long-term anti-inflammatory
      treatment may reduce symptoms and signs and the risk of a mutilating course and
      the development of carcinomas.

PMID- 29340710
TI  - Production of plant-derived polyphenols in microorganisms: current state and
      perspectives.
AB  - Plants synthesize several thousand different polyphenols of which many have the
      potential to aid in preventing or treating cancer, cardiovascular, and
      neurodegenerative diseases. However, plants usually contain complex polyphenol
      mixtures impeding access to individual compounds in larger quantities. In
      contrast, functional integration of biosynthetic plant polyphenol pathways into
      microorganisms allows for the production of individual polyphenols as chemically
      distinct compounds, which can be synthesized in large amounts and can be more
      easily isolated. Over the last decade, microbial synthesis of many plant
      polyphenols could be achieved, and along the way, many decisive bottlenecks in
      the endogenous microbial host metabolism as well as in the heterologous plant
      pathways could be identified. In this review, we present recent advancements in
      metabolic engineering of microorganisms for the production of plant polyphenols
      and discuss how current challenges could be addressed in the future.

PMID- 29340708
TI  - Molecular recognition of microbial lipid-based antigens by T cells.
AB  - The immune system has evolved to protect hosts from pathogens. T cells represent
      a critical component of the immune system by their engagement in host defence
      mechanisms against microbial infections. Our knowledge of the molecular
      recognition by T cells of pathogen-derived peptidic antigens that are presented
      by the major histocompatibility complex glycoproteins is now well established.
      However, lipids represent an additional, distinct chemical class of molecules
      that when presented by the family of CD1 antigen-presenting molecules can serve
      as antigens, and be recognized by specialized subsets of T cells leading to
      antigen-specific activation. Over the past decades, numerous CD1-presented self-
      and bacterial lipid-based antigens have been isolated and characterized. However,
      our understanding at the molecular level of T cell immunity to CD1 molecules
      presenting microbial lipid-based antigens is still largely unexplored. Here, we
      review the insights and the molecular basis underpinning the recognition of
      microbial lipid-based antigens by T cells.

PMID- 29340711
TI  - Microbial degradation of triclosan by a novel strain of Dyella sp.
AB  - A novel strain capable of degrading triclosan was isolated from the acclimated
      activated sludge and identified to be Dyella sp. WW1 based on 16S rDNA analysis.
      The effect of initial concentration of triclosan (0.2, 1, 5, and 10 mg/L),
      temperature (15, 25, and 35  degrees C), pH (5, 7, and 9), and additional carbon
      source on the degradation of triclosan was investigated in a mineral medium. The
      results showed that Dyella sp. WW1 can use triclosan as sole carbon source and
      degrade it when initial triclosan concentration was in the range of 0.2-10 mg/L.
      The optimal condition for Dyella sp. WW1 to degrade triclosan was 15  degrees C
      and pH 7. TOC removal efficiency was more than 90%. Dyella sp. WW1 can degrade
      3,5-dichloro-4-hydrobenzoic via co-metabolism in the presence of triclosan, but
      cannot degrade trimethoprim, sulfamethoxazole, carbamazepine, and diclofenac. In
      the presence of glucose, Dyella sp. WW1 firstly utilized glucose to synthesize
      the biomass and then degraded triclosan. When triclosan concentration decreased
      to an extent (1.2 mg/L in this study), Dyella sp. WW1 started to use glucose
      again. The wastewater components did not significantly affect the activity of
      Dyella sp. WW1 to degrade triclosan. During the biodegradation process, six
      metabolite products were identified. Based on the metabolites, two degradation
      pathways were tentatively proposed. In summary, Dyella sp. WW1 could be used for
      degrading triclosan in the real wastewater.

PMID- 29340713
TI  - Annual Congress of the European Association of Nuclear Medicine Saturday October1
      Wednesday October 3, 2006, Athens Greece.

PMID- 29340712
TI  - Membrane Position Dependency of the pKa and Conductivity of the Protein Ion
      Channel.
AB  - The dependency of current-voltage characteristics of the alpha-hemolysin channel
      on the channel position within the membrane was studied using Poisson-Nernst
      Planck theory of ion conductivity with soft repulsion between mobile ions and
      protein atoms (SP-PNP). The presence of the membrane environment also influences
      the protonation state of the residues at the boundary of the water-lipid
      interface. In this work, we predict that Asp and Lys residues at the protein rim
      change their protonation state upon penetration to the lipid environment. Free
      energies of protein insertion in the membrane for different penetration depths
      were estimated using the Poisson-Boltzmann/solvent-accessible surface area
      (PB/SASA) model. The results show that rectification and reversal potentials are
      very sensitive to the relative position of channel in the membrane, which in turn
      contributes to alternative protonation states of lipid-penetrating ionizable
      groups. The prediction of channel position based on the matching of calculated
      rectification with experimentally determined rectification is in good agreement
      with recent neutron reflection experiments. Based on the results, we conclude
      that alpha-hemolysin membrane position is determined by a combination of factors
      and not only by the pattern of the surface hydrophobicity as is typically
      assumed.

PMID- 29340714
TI  - Taxonomical Resolution and Distribution of Bacterioplankton Along the Vertical
      Gradient Reveals Pronounced Spatiotemporal Patterns in Contrasted Temperate
      Freshwater Lakes.
AB  - We examined the relationship between viruses and co-occurring bacterial
      communities across spatiotemporal scale in two contrasting freshwater lakes,
      namely meromictic Lake Pavin and dimictic Lake Aydat (Central France). Next
      generation sequencing of 16S rRNA genes suggested distinct patterns in
      bacterioplankton community composition (BCC) between the lakes over depths and
      seasons. BCC were generally dominated by members of Actinobacteria,
      Proteobacteria, and Bacteroidetes covering about 95% of all sequences. Oxygen
      depletion at the bottom waters in Aydat and existence of permanent anoxia in the
      monimolimnion of Pavin resulted in the occurrence and dominance of lesser known
      members of lake communities such as Methylotenera, Methylobacter, Gallionella,
      Sulfurimonas, and Syntrophus in Pavin and Methylotenera and Sulfuritalea in
      Aydat. Differences in BCC appeared strongly related to dissolved oxygen
      concentration, temperature, viral infection, and virus-to-bacteria ratio. UniFrac
      analysis indicated a clear distinction in BCC when the percentage of viral
      infected bacterial cells and virus-to-bacteria ratio exceeded a threshold level
      of 10% and 5, respectively, suggesting a link between viruses and their potential
      bacterial host communities. Our study revealed that in both the lakes, the
      prevailing environmental factors across time and space structured and influenced
      the adaptation of bacterial communities to specific ecological niches.

PMID- 29340715
TI  - Postural control and the relation with cervical sensorimotor control in patients
      with idiopathic adult-onset cervical dystonia.
AB  - Cervical dystonia (CD) is a movement disorder characterized by involuntary muscle
      contractions leading to an abnormal head posture or movements of the neck.
      Dysfunctions in somatosensory integration are present and previous data showed
      enlarged postural sway in stance. Postural control during quiet sitting and the
      correlation with cervical sensorimotor control were investigated. Postural
      control during quiet sitting was measured via body sway parameters in 23 patients
      with CD, regularly receiving botulinum toxin treatment and compared with 36
      healthy controls. Amplitude and velocity of displacements of the center of
      pressure (CoP) were measured by two embedded force plates at 1000 Hz. Three
      samples of 30 s were recorded with the eyes open and closed. Disease-specific
      characteristics were obtained in all patients by the Tsui scale, Cervical
      Dystonia Impact Profile (CDIP-58) and Toronto Western Spasmodic Rating Scale
      (TWSTRS). Cervical sensorimotor control was assessed with an infrared Vicon
      system during a head repositioning task. Body sway amplitude and velocity were
      increased in patients with CD compared to healthy controls. CoP displacements
      were doubled in patients without head tremor and tripled in patients with a
      dystonic head tremor. Impairments in cervical sensorimotor control were
      correlated with larger CoP displacements (rs ranged from 0.608 to 0.748).
      Postural control is impaired and correlates with dysfunction in cervical
      sensorimotor control in patients with CD. Treatment is currently focused on the
      cervical area. Further research towards the potential value of postural control
      exercises is recommended.

PMID- 29340716
TI  - Congenital blindness limits allocentric to egocentric switching ability.
AB  - Many everyday spatial activities require the cooperation or switching between
      egocentric (subject-to-object) and allocentric (object-to-object) spatial
      representations. The literature on blind people has reported that the lack of
      vision (congenital blindness) may limit the capacity to represent allocentric
      spatial information. However, research has mainly focused on the selective
      involvement of egocentric or allocentric representations, not the switching
      between them. Here we investigated the effect of visual deprivation on the
      ability to switch between spatial frames of reference. To this aim, congenitally
      blind (long-term visual deprivation), blindfolded sighted (temporary visual
      deprivation) and sighted (full visual availability) participants were compared on
      the Ego-Allo switching task. This task assessed the capacity to verbally judge
      the relative distances between memorized stimuli in switching (from egocentric-to
      allocentric: Ego-Allo; from allocentric-to-egocentric: Allo-Ego) and non
      switching (only-egocentric: Ego-Ego; only-allocentric: Allo-Allo) conditions.
      Results showed a difficulty in congenitally blind participants when switching
      from allocentric to egocentric representations, not when the first anchor point
      was egocentric. In line with previous results, a deficit in processing
      allocentric representations in non-switching conditions also emerged. These
      findings suggest that the allocentric deficit in congenital blindness may
      determine a difficulty in simultaneously maintaining and combining different
      spatial representations. This deficit alters the capacity to switch between
      reference frames specifically when the first anchor point is external and not
      body-centered.

PMID- 29340717
TI  - Evaluation of left ventricular function after percutaneous recanalization of
      chronic coronary occlusions : The role of two-dimensional speckle tracking
      echocardiography.
AB  - BACKGROUND: This study evaluated the feasibility of using two-dimensional speckle
      tracking echocardiography (2D-STE) to monitor left ventricular (LV) and overall
      function after percutaneous recanalization. METHODS: LV function after
      percutaneous recanalization was monitored by 2D-STE and conventional
      echocardiography in 43 patients with coronary chronic total occlusion (CTO) who
      underwent primary percutaneous coronary intervention (PCI). Follow-ups were
      carried out 1 day as well as 3 and 6 months after CTO-PCI. At each time point, LV
      ejection fraction (LVEF) was examined by echocardiography, and LV global
      longitudinal strain (GLS) was measured by 2D-STE. RESULTS: It was found that the
      global longitudinal strain assessed with 2D-STE was improved as early as 1 day
      after CTO-PCI, whereas LVEF tended to improve up to 3 and 6 months after CTO-PCI.
      CONCLUSION: PCI can effectively improve LV function in patients with CTO. 2D-STE
      is a superior technique for objectively quantifying the functional change
      earlier.

PMID- 29340718
TI  - Drug treatment of heart failure in the elderly.
AB  - The prevalence of heart failure increases with age. Changes in the age
      distribution and growing life expectancy will lead to a further rise. However,
      data concerning drug treatment of heart failure especially in the elderly are
      scarce. Subgroup analyses of the heart failure trials suggest that drug therapy
      in older patients should follow the recommendations in the current guidelines. In
      doing so, several common comorbidities in these patients (e. g., impaired renal
      function) have to be considered and may have an influence on the therapy (e. g.,
      drug dose, choice of active pharmaceutical ingredient, etc.). Especially in old,
      multimorbid patients, possible interaction of drugs might play a substantial
      role. In many cases the main goal of the therapy, especially in the very elderly,
      is to improve symptoms and quality of life.

PMID- 29340719
TI  - Treatment with 48-mm everolimus-eluting stents : Procedural safety and 12-month
      patient outcome.
AB  - BACKGROUND: Lesion length is a major predictor of adverse outcomes after
      percutaneous coronary intervention. Long lesions often require multiple stents
      with variable overlap, which increases the probability of geographical miss and
      the incidence of mechanical complications, such as side-branch occlusion,
      restenosis, and stent thrombosis. These pitfalls may be avoided by use of an
      ultra-long device. METHODS: We retrospectively assessed the performance of the 48
      mm Xience Xpedition everolimus-eluting stent (EES) at our institution. RESULTS: A
      total of 123 patients (mean age: 60.94 years, n = 93 [76%] male) with 129 lesions
      were identified. Lesions (n = 69, 53.5%) were located in the left anterior
      descending artery, the right coronary artery (n = 47, 36.4%), and the circumflex
      artery (n = 8, 6.2%); 83 lesions involved a major side branch. The majority were
      treated with a provisional single-stent strategy. Other characteristics included
      significant tortuosity in 15 lesions (11.6%) and moderate-to-heavy calcification
      in 46 lesions (35.7%). In all cases, balloon pre-dilatation was performed before
      stent insertion. Successful delivery and deployment of the 48-mm EES device was
      achieved in 100% of the patients. The mean number of stents per lesion was 1.4,
      while the mean total stent length was 58 +/- 17.3 mm and mean stent diameter,
      3.00 +/- 0.67 mm. The procedural success rate was 99.2%. The 30-day major cardiac
      adverse event (MACE) rate was 0.8%, while the 12-month MACE was 3.3%. CONCLUSION:
      The Xience 48-mm EES device appears to be safe and efficacious with a low
      clinical event rate at the 12-month follow-up. Where feasible, this would support
      the use of the ultra-long 48-mm platform in lieu of multiple overlapping shorter
      devices.

PMID- 29340720
TI  - Correction to: Polymyxin B-immobilized hemoperfusion and mortality in critically
      ill adult patients with sepsis/septic shock: a systematic review with meta
      analysis and trial sequential analysis.
AB  - Owing to an oversight by the authors, Figure 2 in this article was not the
      version intended for publication. The correct Figure 2, reproduced here, features
      footnote symbols and Figure 2b includes three studies as described in the main
      text.

PMID- 29340721
TI  - Geochemical Assessment of Fluoride Pollution in Groundwater of Tribal Region in
      India.
AB  - This study assessed the fluoride (F-) pollution in groundwater samples (n = 170)
      of tribal regions around Bailadila Iron Ore Mines [BIOM] Complex of Dantewada
      District, India. Weathering of carbonate and silicate clays were important
      geogenic sources of dissolved ions. A Piper diagram showed a Ca-HCO3 water type,
      with positive chloro-alkaline indices illustrating the occurrence of direct base
      exchange reactions. The F- concentrations varied from 0.08 to 1.95 mg L-1 with a
      mean value of 0.9 +/- 0.3 mg L-1. Only two groundwater samples showed F-
      concentrations > 1.5 mg L-1, the drinking water guideline established by the
      World Health Organization (WHO) and Bureau of Indian Standards (BIS). Factor
      analysis showed high loadings of HCO3- and F-, indicating alkaline conditions,
      favoring the dissolution of F- in the groundwater. The K fluor value is less than
      10-10.6, indicating that the dissociation of fluorite is very slow. As a result,
      groundwater locations were under-saturated with respect to fluorite.

PMID- 29340722
TI  - New frontiers and cutting edge applications in ultra high performance liquid
      chromatography through latest generation superficially porous particles with
      particular emphasis to the field of chiral separations.
AB  - About ten years after their introduction to the market (happened in 2006), the so
      called second generation superficially porous particles (SPPs) have undoubtedly
      become the benchmark as well as, very often, the preferred choice for many
      applications in liquid chromatography (LC), when high efficiency and fast
      separations are required. This trend has interested practically all kinds of
      separations, with the only exception of chiral chromatography (at least so far).
      The technology of production of base SPPs is advanced, relatively simple and
      widely available. The deep investigation of mass transfer mechanisms under
      reversed-phase (RP) and normal-phase (NP) conditions for achiral separations has
      shown the advantages in the use of these particles over their fully porous
      counterparts. In addition, it has been demonstrated that SPPs are extremely
      suitable for the preparation of efficient packed beds through slurry packing
      techniques. However, the research in this field is in continual evolution. In
      this article, some of the most advanced concepts and modern applications based on
      the use of SPPs, embracing in particular ultrafast chiral chromatography and the
      design of SPPs with engineered pore structures or very reduced particle diameter,
      are revised. We describe modern trends in these fields and focus on those aspect
      where further innovation and research will be required. Graphical Abstract Word
      cloud of cutting edge applications of superficially porous particles in liquid
      chromatography.

PMID- 29340723
TI  - Veno-Venous Extracorporeal Membrane Oxygenation (VV ECMO) for Acute Respiratory
      Failure Following Injury: Outcomes in a High-Volume Adult Trauma Center with a
      Dedicated Unit for VV ECMO.
AB  - INTRODUCTION: The use of veno-venous extracorporeal membrane oxygenation (VV
      ECMO) has increased over the past decade. The purpose of this study was to
      evaluate outcomes in adult trauma patients requiring VV ECMO. METHODS: Data were
      collected on adult trauma patients admitted between January 1, 2015, and November
      1, 2016. Demographics, injury-specific data, ECMO data, and survival to discharge
      were recorded. Medians [interquartile range (IQR)] were reported. A p value
      <=0.05 was considered statistically significant. RESULTS: Eighteen patients
      required VV ECMO during the study period. Median age was 28.5 years (IQR 24-43).
      Median injury severity score (ISS) was 27 (IQR 21-41); median PaO2/FiO2 (P/F)
      prior to ECMO cannulation was 61 (IQR 50-70). Median time from injury to
      cannulation was 3 (IQR 0-6) days. Median duration of ECMO was 266 (IQR 177-379)
      hours. Survival to discharge was 78%. Survivors had a significantly higher ISS (p
      = 0.03), longer intensive care unit length of stay (ICU LOS) (p < 0.0004),
      hospital LOS (p < 0.000004), and time on the ventilator (p < 0.0003). Median time
      of injury to cannulation was significantly longer in patients who survived to
      discharge (p = 0.01). There was no difference in P/F ratio prior to cannulation
      (p = ns). CONCLUSION: We have demonstrated improved outcome of patients requiring
      VV ECMO following injury compared to historical data. Although shorter time from
      injury to cannulation for VV ECMO was associated with death, select patients who
      meet criteria for VV ECMO early following injury should be referred/transferred
      to a tertiary care facility that specializes in trauma and ECMO care.

PMID- 29340724
TI  - The Role of Surgery in Treating Resectable Limited Disease of Esophageal
      Neuroendocrine Carcinoma.
AB  - BACKGROUND: Esophageal neuroendocrine carcinoma (NEC) is a rare malignant tumor.
      The role of surgery in resectable limited disease of esophageal NEC remains
      unclear. How to select a specific group of limited disease of esophageal NEC who
      might benefit from surgery remains to be answered. METHODS: Patients undergoing
      esophagectomy for resectable limited disease of esophageal NEC in our department
      from January 2007 to June 2015 were analyzed. TNM staging system was applied to
      describe those patients, and according to their different long-term prognosis
      after surgery, those patients were subgrouped into surgery response limited
      disease (SRLD) group and surgery non-response limited disease (SNRLD) group. Both
      univariate and multivariate analyses were applied to identify potential
      prognostic factors. RESULTS: A total of 72 patients with resectable limited
      disease of esophageal NEC were identified for analysis. The median survival time
      of those patients was 21.5 months. There was no significant survival differences
      among stage I, stage IIA, and stage IIB patients, but all these patients had
      significantly longer survival than stage III patients. Therefore, stage I, stage
      IIA, and stage IIB patients were aggregated together as SRLD group, and stage III
      patients were aggregated as SNRLD group. SRLD patients obtained significantly
      longer survival than SNRLD patients in both univariate analysis and multivariate
      analysis. Moreover, adjuvant therapy could significantly benefit SRLD patients (P
      = 0.004) but could not benefit SNRLD patients (P = 0.136). CONCLUSIONS: Different
      responses to surgery existed in resectable limited disease of esophageal NEC
      indicating the need of further subgrouping for those patients. The resectable
      limited disease of esophageal NEC could be further subgrouped into SRLD group and
      SNRLD group according to the TNM staging system.

PMID- 29340725
TI  - Decision-Making in Management of the Complex Trauma Patient: Changing the Mindset
      of the non-trauma Surgeon.
AB  - BACKGROUND: European surgeons are frequently subspecialized and trained primarily
      in elective surgical techniques. As trauma leaders, they may occasionally have to
      deal with complex polytrauma, advanced management techniques, differing
      priorities, and the need for multidisciplinary care. There is a lack of
      expertise, experience, and a low trauma volume, as well as a lack of research,
      with limited support as to the decision-making and teaching challenges present.
      We studied what experienced trauma experts describe as the challenges that are
      specific to the advanced surgical decision-making required, whether civilian,
      humanitarian, or military. METHODS: Design-based research using combined methods
      including interviews, reviews of authentic trauma cases, and video-recorded
      resuscitations performed at a high-volume civilian academic trauma center.
      RESULTS: Several educational dilemmas were identified: (1) thinking
      physiologically, (2) the application of damage control resuscitation and surgery,
      (3) differing priorities and time management, (4) impact of environment, (5)
      managing limited resources, (6) lack of general surgical skills, (7) different
      cultural behavior, and (8) ethical issues. CONCLUSION: The challenges presented,
      and the educational domains identified, constitute a basis for improved
      development of education and training in complex surgical decision-making. This
      study contributes new knowledge about the mindset required for decision-making in
      patients with complex multisystem trauma and competing priorities of care. This
      is, especially important in countries having a low intensity of trauma in both
      military and civilian environments, and consequential limited skills, and lack of
      expertise. Guidelines focused on the same decision-making process, using virtual
      patients and blended learning, can be developed.

PMID- 29340726
TI  - Prognostic Prediction Models for Resection of Large Hepatocellular Carcinoma: A
      Korean Multicenter Study.
AB  - BACKGROUND: We developed a prognostic prediction model (PPM) using 4 factors for
      hepatic resection (HR) of large hepatic cellular carcinoma (HCC). Multiplication
      of alpha-fetoprotein (AFP), des-gamma-carboxy prothrombin, and tumor volume (TV)
      (ADV score) is a surrogate marker for post-resection prognosis. This study
      intended to validate the predictive power of 4-factor PPM and to develop new ADV
      score-based PPM. METHODS: A total of 526 patients who underwent HR for solitary
      HCC >= 8 cm were selected from 9 Korean institutions between 2008 and 2014.
      RESULTS: Median tumor diameter and TV were 11.0 cm and 398 mL, respectively.
      Tumor recurrence and patient survival rates were 53.0 and 78.4% at 1 year and
      70.2 and 49.3% at 5 years, respectively. Independent risk factors for both tumor
      recurrence and patient survival included AFP >= 100 ng/mL, hypermetabolic FDG
      positron emission tomography (PET), microvascular invasion and satellite nodules,
      which comprised 4 factors of the PPM. Five subgroups based on the number of
      involved risk factors exhibited significant differences in tumor recurrence and
      patient survival. ADV score cutoff was set at 7log (ADV7log) after cluster
      prognostic analysis. Patient grouping according to combination of ADV7log and FDG
      PET findings (ADV7log-PET) exhibited significant differences in tumor recurrence
      and patient survival, comparable to those of the 4-factor PPM. CONCLUSIONS: Two
      PPMs using 4 risk factors and ADV7log-PET could reliably predict the risk of
      early HCC recurrence and long-term survival outcomes in patients who underwent HR
      for large HCC. We believe that these PPMs can guide surgical treatment for large
      HCCs from preoperative HR planning to post-resection follow-up.

PMID- 29340727
TI  - Parastomal Hernia Repair with a 3D Funnel Intraperitoneal Mesh Device and Same
      Sided Stoma Relocation: Results of 56 Cases: Reply.

PMID- 29340729
TI  - Pulmonary Valve Morphology in Patients with Bicuspid Aortic Valves.
AB  - The aortic and pulmonary valve share a common developmental origin from the
      embryonic arterial trunk. Bicuspid aortic valve is the most common congenital
      anomaly and can occur isolated as well as in association with other congenital
      heart disease (CHD). Data on pulmonary valve morphology in these cases are
      scarce. In this study, we aimed to determine pulmonary valve morphology in hearts
      with BAV associated with CHD. In 83 post-mortem heart specimens with BAV and
      associated CHD, pulmonary valve morphology was studied and related to BAV
      morphology. In 14/83 (17%) hearts, the pulmonary valve was affected, bicuspid in
      8/83 (10%), dome-shaped in 3/83 (4%) and atretic in 3/83 (4%). In specimens with
      a bicuspid pulmonary valve, 5/8 (63%) had a strictly bicuspid aortic valve
      (without raphe), 2/3 hearts (67%) with dome-shaped pulmonary valves and 2/3
      hearts (67%) with atretic pulmonary valves had BAV without raphe. Six out of
      eight (75%) specimens with a bicuspid pulmonary valve had a perimembranous
      ventricular septal defect (VSD). 4/8 (50%) specimens with a bicuspid pulmonary
      valve were associated with chromosomal abnormalities: 3 (38%) had trisomy 18 and
      1 (13%) had trisomy 13. In BAV with associated CHD, abnormal pulmonary valve
      morphology was observed in 17% of the hearts. The majority of hearts with
      abnormal pulmonary valve morphology had a Type B bicuspid aortic valve (without
      raphe). Bilateral semilunar valvular disease is associated with Type B BAVs and
      in many cases related to chromosomal abnormalities. As this study was performed
      in post-mortem specimens with high frequency of associated CHD, caution is
      warranted with application of these results to the general BAV population.

PMID- 29340728
TI  - Indocyanine Green Retention Rates at 15 min Predicted Hepatic Decompensation in a
      Western Population.
AB  - BACKGROUND: ICGR15 is widely used in Asia to evaluate the liver reserve before
      hepatectomy, but not in Western countries where patients are selected using the
      MELD score and/or platelet count. Postoperative liver failure is rare nowadays,
      but hepatic decompensation (HD), defined by 3-month postoperative ascites,
      impairs quality of life and survival. The aim of this study was to evaluate the
      relevance of indocyanine green retention rate at 15 min (ICGR15) before liver
      resection in Western countries, in order to predict HD. METHODS: This
      prospectively designed study included consecutive adult patients undergoing
      hepatectomy for hepatocellular carcinoma (HCC) and intrahepatic
      cholangiocarcinoma (ICC) in three French HPB centres. RESULTS: Between 2012 and
      2014, 147 patients were included (80% of HCC and 20% of ICC). The Child-Pugh
      status was grade A for all patients. In the overall population and in F3/F4
      patients (n = 83), ICGR15 (P = 0.02) and platelet counts (P = 0.02) were
      predictive of HD under multivariate analysis. Among F3/F4 patients undergoing
      minor hepatectomy with preoperative ICGR15 > 15%, the rate of HD was 36%. In the
      overall population, ICGR15 was predictive of HD (P = 0.02) and postoperative
      ascites (P = 0.03). The ROC curve identified a cut-off point of 15% as being
      associated with increased HD, with good accuracy for ICGR15 in the study
      population (AUROC 0.73), mainly before minor hepatectomy (AUROC 0.79).
      CONCLUSIONS: In patients with HCC and ICC selected using the MELD score and
      platelet rate, an ICGR15 > 15% is a relevant, non-invasive and clearly accurate
      method to predict HD specially before minor hepatectomy.

PMID- 29340730
TI  - Age-Dependent Association Between Pre-transplant Blood Transfusion and Outcomes
      of Pediatric Heart Transplantation.
AB  - Avoidance of red blood cell (RBC) transfusions in patients awaiting heart
      transplantation (HTx) has been suggested to minimize the risk of
      allosensitization. Although recent studies have suggested that an immature immune
      system in younger HTx recipients may reduce risks associated with RBC
      transfusion, the role of age in moderating the influence of transfusion on HTx
      outcomes remains unclear. We used available data from a national transplant
      registry to explore whether the association between pre-transplant transfusions
      and outcomes of pediatric HTx varies by patient age. De-identified data were
      obtained from the United Network for Organ Sharing registry, including first-time
      recipients of isolated HTx performed at age 0-17 years in 1995-2015. The primary
      exposure was receiving blood transfusions within 2 weeks prior to HTx. Patient
      survival after HTx was evaluated using multivariable Cox proportional hazards,
      where age at transplant was interacted with exposure to pre-transplant
      transfusion. Age-specific hazard ratios (HRs) of pre-transplant transfusion were
      plotted across ages at transplant. There were 4883 patients meeting inclusion
      criteria, of whom 1258 died during follow-up (mean follow-up duration 6 +/- 5
      years). Patients receiving pre-transplant transfusions were distinguished by
      younger age, higher prevalence of prior cardiac surgery, greater likelihood of
      being in the intensive care unit, and greater use of left ventricular assist
      device bridge to transplant. In multivariable analysis, pre-transplant
      transfusions were associated with increased mortality hazard among infants < 1
      year of age (HR = 1.46; 95% CI 1.23, 1.74; p < 0.001). For each additional year
      of age, the excess hazard associated with pre-transplant transfusions decreased
      by 3% (interaction HR = 0.97; 95% CI 0.98, 0.99; p = 0.003). By age 8, the
      association between pre-transplant transfusions and post-transplant mortality was
      no longer statistically significant (HR = 1.15; 95% CI 0.99, 1.32; p = 0.060).
      Pre-transplant transfusions were associated with increased mortality hazard only
      among younger children (age < 8 years) undergoing HTx. These data support the
      current practices of transfusion avoidance prior to HTx, particularly in younger
      patients.

PMID- 29340732
TI  - [Electronic decision support to promote medication safety].
AB  - Because of its inherent complexity, it is a considerable challenge to tailor drug
      treatment to a prevalent disease and its subgroups, which are increasingly
      defined by genomic variability (personalized medicine) and require consideration
      of context information such as co-morbidity, co-medication, patient preferences,
      and the specific characteristics of the healthcare sector. Thus, optimum
      treatment decisions might not be taken intuitively any longer, because decisions
      must be made both rapidly and increasingly based on analyses of complex relations
      of numerous variables that exceed the processing performance of a human brain.
      Hence, computer support is indispensable to ensure error-free high-performance
      medicine. A key step in computer-supported medication safety is to implement a
      computerized physician order entry (CPOE) system that compiles a patient's
      medication in a structured and coded format enabling the link to clinical
      decision support (CDS) systems. Implementing a CPOE is hence a strategic step for
      a hospital, which is crucial to exhaustingly and consistently prevent medication
      errors. Thereby, the best performance of a CPOE is achieved if it is deeply
      integrated into an electronic patient record thus enabling access to relevant
      patient information, which again has to be structured to allow processing. To
      efficiently support drug treatment, CDS systems must fulfill high-quality
      standards with regard to underlying data, integration, and user-interaction to
      ensure that they support but do not impede the provision of care.

PMID- 29340731
TI  - Sensitive Cardiac Troponins: Could They Be New Biomarkers in Pediatric Pulmonary
      Hypertension Due to Congenital Heart Disease?
AB  - To analyze the role of sensitive cardiac troponin I (scTnI) and high-sensitive
      troponin T (hscTnT) in the determination of myocardial injury caused by volume
      and pressure load due to pulmonary hypertension (PH) and to investigate if these
      markers may be useful in the management of PH in childhood. Twenty-eight patients
      with congenital heart disease (CHD) with left to right shunt and PH, 29 patients
      with CHD with left to right shunt but without PH, and 18 healthy children, in
      total 75 individuals, were included in the study. All cases were aged between 4
      and 36 months. Echocardiographic evaluation was performed in all cases, and
      invasive hemodynamic investigation was performed in 33 cases. Blood samples were
      obtained from all cases, for the measurement of brain natriuretic peptide (BNP),
      pro-brain natriuretic peptide (pro-BNP), sensitive cardiac troponin I (scTnI),
      and high-sensitive troponin T (hscTnT) levels. The mean BNP, pro-BNP, scTnI, and
      hsTnT levels were statistically significantly higher in patients with PH than in
      the patients without PH (p < 0.001). A statistically significant positive
      correlation was determined between pulmonary artery systolic pressure and scTnI
      and hscTnT levels (r = 0.34 p = 0.01, r = 0.46 p < 0.001, respectively) levels.
      Pulmonary hypertension determined in congenital heart diseases triggers
      myocardial damage independently of increased volume or pressure load and
      resistance, occurring by disrupting the perfusion via increasing ventricular wall
      tension and the myocardial oxygen requirement. Serum scTnI and hscTnT levels may
      be helpful markers to determine the damage associated with PH in childhood.

PMID- 29340737
TI  - [Rhinoplasty-state of the art].

PMID- 29340736
TI  - Risk factors for early infection following hemiarthroplasty in elderly patients
      with a femoral neck fracture.
AB  - PURPOSE: Periprosthetic joint infections (PJI) after hemiarthroplasty for
      geriatric femoral neck fractures are a devastating complication that results in
      serious morbidity and increased mortality. Identifying risk factors associated
      with early infection after HA for hip fractures may offer an opportunity to
      address and prevent this complication in many patients. The aim of this study was
      to evaluate preoperative risk factors for early PJI after HA in hip fracture
      patients. METHODS: From January 2010 to December 2015, 312 femoral neck fractures
      (AO/OTA 31-B) in 305 patients were included in this single-center, retrospective
      study. PJI was defined according to the Centers for Disease Control (CDC)
      definition of deep incisional surgical site infection. Early infection referred
      to a postoperative period of 4 weeks. Binary univariable and multivariable
      regression analysis with backward elimination was applied to identify predictors
      of PJI. RESULTS: Median age of all patients was 83.0 (IQR 76-89) years. We
      identified 16 (5.1%) early PJI which all required surgical revision. Median
      length of in-hospital stay (LOS) was 20.0 (IQR 10-36) days after PJI compared to
      10.0 (8-15) days without deep wound infection. In-hospital mortality was 30.8 vs.
      6.6%, respectively. Preoperative CRP levels (OR 1.009; 95% CI 1.002-1.018; p =
      0.044), higher BMI (OR 1.092; 95% CI 1.002-1.189; p = 0.044) and prolonged
      surgery time (OR 1.013; 95% CI 1.000-1.025; p = 0.041) were independent risk
      factors for PJI. Excluding infection following major revision due to mechanical
      complications identified preoperative CRP levels (OR 1.012; 95% CI 1.003-1.021; p
      = 0.007) and chronic glucocorticoid therapy (OR 6.314; 95% CI 1.223-32.587; p =
      0.028) as risk factors, a clear trend was seen for higher BMI (OR 1.114; 95% CI
      1.000-1.242; p = 0.051). A cut-off value at CRP levels >= 14 mg/l demonstrated a
      sensitivity of 69% and a specificity of 70% with a fair accuracy (AUC 0.707).
      CONCLUSION: Preoperative serum CRP levels, higher BMI and prolonged surgery time
      are independent predictors of early PJI. Excluding PJI secondary to major
      revision surgery revealed chronic glucocorticoid use as a risk factor apart from
      preoperative CRP levels.

PMID- 29340733
TI  - Population pharmacokinetics of lamotrigine co-administered with valproic acid in
      Chinese epileptic children using nonlinear mixed effects modeling.
AB  - PURPOSE: The aims of this study were to develop a population pharmacokinetic
      (PPK) model of lamotrigine (LTG) in Chinese epileptic children by using nonlinear
      mixed effects modeling (NONMEM) and to investigate the effects of valproic acid
      (VPA) and genetic polymorphisms of the major metabolizing enzymes (UGT1A4,
      UGT2B7) on the pharmacokinetics of LTG. METHODS: A total of 182 epileptic
      children who were treated with LTG as monotherapy or as part of combination
      therapy were included in this study as the model group, and 61 patients were
      included as the validation group. The steady-state serum trough concentrations of
      LTG and VPA were determined using a high-performance liquid chromatography method
      and fluorescence polarization immunoassay, respectively. Patients were genotyped
      for three single nucleotide polymorphisms (UGT1A4 142T>G, UGT2B7 -161C>T, and
      UGT2B7 802C>T). PPK analysis was performed with NONMEM using first-order
      absorption and elimination. Bootstrap, normalized prediction distribution errors
      and external evaluations were performed to determine the stability and predictive
      performance of the model. RESULTS: For the final model, the oral clearance (CL/F)
      of LTG was estimated to be 0.705 L/h with inter-individual variability (IIV) of
      21.3%. The estimates generated by NONMEM indicated that the LTG CL/F was
      significantly influenced by patient body weight (increased with an exponent of
      0.574) and VPA concentration (decreased with linearity of 0.273 with co
      administration). However, no significant effects of UGT1A4 or UGT2B7
      polymorphisms on LTG CL/F were noted in this population of Chinese children.
      CONCLUSION: This study confirms the interaction of LTG with VPA, which likely
      depends on VPA concentration. The LTG PPK model developed in this study could be
      useful for individualizing LTG dosage regimens in pediatric patients receiving
      combination therapy, especially therapy that includes VPA.

PMID- 29340738
TI  - ?

PMID- 29340739
TI  - ?

PMID- 29340740
TI  - [Paraneoplastic syndromes in rheumatology].
AB  - Malignancies can present as inflammatory rheumatic diseases. These rheumatic
      paraneoplastic syndromes are rare, but characteristic in their pattern. This
      article focuses on epidemiology, clinical and diagnostic features as well as
      treatment of paraneoplasic rheumatic diseases such as paraneoplastic arthritides,
      vasculitides, myositis and hypertrophic osteoarthropathy. The knowledge of their
      clinical patterns is of utmost importance for early diagnosis and prognosis of
      yet undiagnosed malignancies.

PMID- 29340741
TI  - [Platelet inhibition in patients with coronary, cerebral and peripheral
      macroangiopathy : What, when and how long?]
AB  - BACKGROUND: Inhibition of platelet aggregation can reduce the rate of vascular
      events in patients with coronary artery disease, carotid artery stenosis and
      symptomatic peripheral arterial disease. The choice of platelet inhibitors in
      monotherapy and combination therapy as well as the duration of dual platelet
      inhibition depend on the clinical situation and individual patient
      characteristics. GOAL: The present review summarizes the latest data from
      clinical trials and recommendations regarding platelet inhibition in coronary,
      cerebral and peripheral arterial disease. DATA: A large number of randomized
      trials on platelet inhibition in different clinical situations have been
      performed, allowing evidence-based recommendations on the choice of drugs and
      duration of treatment. Moreover, new guidelines of European professional
      societies on platelet inhibition in patients with coronary, cerebral and
      peripheral arterial disease have been recently published. CONCLUSION: Based on
      latest randomized trials and major society guidelines, a number of
      recommendations on platelet inhibition in stable coronary artery disease, after
      stent implantation, after acute coronary syndromes and in cerebral and peripheral
      arterial disease can be made.

PMID- 29340742
TI  - [Wilson disease].
AB  - Wilson disease is a rare hereditary disorder of copper metabolism. The genetic
      defect is caused by various mutations in the copper-transporting enzyme ATP7B,
      located mainly in the liver and brain. Clinical symptoms are highly variable,
      with any combination of hepatic and/or neurological or psychiatric
      manifestations. The age of onset varies from early childhood to young adults and
      can even be manifested in later ages. The clinical diagnosis is based on a
      combination of clinical, biochemical and molecular markers. Treatment using
      chelating agents and zinc salts is effective when started early or even better at
      presymptomatic stages of the disease.

PMID- 29340743
TI  - Recent Trends and Advances in Cancer-Induced Bone Disease.

PMID- 29340744
TI  - Highlight report: 'Big data in the 3R's: outlook and recommendations', a
      roundtable summary.

PMID- 29340745
TI  - A 6-week warm-up injury prevention programme results in minimal biomechanical
      changes during jump landings: a randomized controlled trial.
AB  - PURPOSE: To examine the extent to which an ACL injury prevention programme
      modifies lower extremity biomechanics during single- and double-leg landing tasks
      in both the sagittal and frontal plane. It was hypothesized that the training
      programme would elicit improvements in lower extremity biomechanics, but that
      these improvements would be greater during a double-leg sagittal plane landing
      task than tasks performed on a single leg or in the frontal plane. METHODS:
      Ninety-seven competitive multi-directional sport athletes that competed at the
      middle- or high-school level were cluster randomized into intervention (n = 48,
      age = 15.4 +/- 1.0 years, height = 1.7 +/- 0.07 m, mass = 59.9 +/- 11.0 kg) and
      control (n = 49, age = 15.7 +/- 1.6 years, height = 1.7 +/- 0.06 m, mass = 60.4
      +/- 7.7 kg) groups. The intervention group participated in an established 6-week
      warm-up-based ACL injury prevention programme. Three-dimensional biomechanical
      analyses of a double- (SAG-DL) and single-leg (SAG-SL) sagittal, and double-
      (FRONT-DL) and single-leg (FRONT-SL) frontal plane jump landing tasks were tested
      before and after the intervention. Peak angles, excursions, and external joint
      moments were analysed for group differences using 2 (group) * 4 (task) repeated
      measures MANOVA models of delta scores (post-pre-test value) (alpha < 0.05).
      RESULTS: Relative to the control group, no significant biomechanical changes were
      identified in the intervention group for any of the tasks (n.s.). However, a
      group by task interaction was identified for knee abduction (lambda = 0.80, p =
      0.02), such that participants in the intervention group showed relative decreases
      in knee abduction moments during the SAG-DL compared to the SAG-SL (p = 0.005; d
      = 0.45, CI = 0.04-0.85) task. CONCLUSION: A 6-week warm-up-based ACL injury
      prevention programme resulted in no significant biomechanical changes during a
      variety of multi-directional jump landings. Clinically, future prevention
      programmes should provide a greater training stimulus (intensity, volume), more
      specificity to tasks associated with the mechanism of ACL injury (single-leg, non
      sagittal plane jump landings), and longer programme duration (> 6 weeks) to
      elicit meaningful biomechanical changes. LEVEL OF EVIDENCE: I.

PMID- 29340746
TI  - Similar clinical outcomes following collagen or polyurethane meniscal scaffold
      implantation: a systematic review.
AB  - PURPOSE: The purpose of this systematic review is to evaluate the current
      literature in an effort to assess specific clinical outcomes following meniscal
      scaffold implantation using the two available scaffolds: Collagen Meniscal
      Implant (CMI) and the Actifit polyurethane meniscal scaffold. METHODS: A
      systematic review was performed by searching PubMed, Embase, and Cochrane Library
      to find studies evaluating clinical outcomes of patients undergoing meniscal
      scaffold implantation. Search terms used were "meniscus", "meniscal", "scaffold",
      and "implant". Studies were evaluated based on scaffold type, treatment failure
      rates, patient-reported outcome scores, concomitant procedures, and radiological
      findings. Radiological findings were recorded using the Genovese scale to assess
      morphology and signal intensity and the Yulish score to assess articular
      cartilage. RESULTS: Nineteen studies (1 level I, 1 level II, 17 level IV
      evidence) were identified that met inclusion criteria, including a total of 658
      patients (347 Actifit, 311 CMI). The overall average follow-up was 45 months.
      Treatment failure occurred in 9.9% of patients receiving the Actifit scaffold at
      a mean follow-up of 40 months and 6.7% of patients receiving CMI at a mean follow
      up of 44 months (n.s.). However, the rate of failure ranged from 0 to 31.8%
      amongst the included studies with a variable definition of failure. Additionally,
      overlapping patients and presence of concomitant surgeries such as anterior
      cruciate ligament reconstruction (ACLR) and high tibial osteotomy (HTO) may have
      a significant influence on these results. Outcomes for the Visual Analog Scale
      (VAS) for pain, Lysholm knee score, and Tegner activity score improved from
      preoperatively to latest follow-up in both groups, while the Knee Injury and
      Osteoarthritis Outcome Score and International Knee Documentation Committee
      scores improved from preoperatively to latest follow-up for Actifit scaffold
      patients. Overall, patients receiving CMI scaffolds had higher grades for
      Genovese morphology and signal intensity when compared to Actifit scaffold
      patients. CONCLUSION: Patients undergoing meniscal scaffold implantation with
      either CMI or Actifit scaffold can both be expected to experience improvement in
      clinical outcomes when used in association with concomitant procedures such as
      ACLR and HTO. LEVEL OF EVIDENCE: IV, systematic review.

PMID- 29340747
TI  - The role of muscle function after anterior cruciate ligament rupture and
      treatment.

PMID- 29340749
TI  - In Pursuit of Effective Volume Reduction and Enhanced Aesthetics for Treatment of
      Gigantomastia Using Superior Dermoglandular Pedicle.
AB  - BACKGROUND: Gigantomastia is defined as extreme hypertrophy of the female breast.
      It is a disabling condition that presents unique challenges to plastic surgeons.
      Initial breast volume is an important factor affecting the success of the
      reduction. Usually, it is difficult to achieve small-sized breasts, and long-term
      results are often unsatisfactory, resulting in complications such as "bottoming
      out" deformities. METHODS: This paper presents a case series involving 40
      patients (mean age 44.2 +/- 12.5) with gigantomastia. Reductions were performed
      by superior nipple-areola complex pedicle with or without liposuction. Total
      resection weight ranged from 2050 to 5398 g (mean 3066 +/- 944.2). Generally, the
      literature emphasizes the unreliability of the long superior pedicle when used to
      reduce the size of very large breasts. The technical steps for this procedure
      have been clearly described, and ways in which to overcome technical difficulties
      and attain effective volume reduction with minimal complications were presented.
      RESULTS: The technique described here is applicable to all gigantomastia cases;
      even very large, pendulous breasts could be effectively reduced. Physical
      symptoms rapidly improved during the early postoperative period, patients'
      aesthetic satisfaction scores were high (4.6/5), and none of the patients
      complained of flat breasts. The rate of partial areola necrosis was 5%, and the
      rate of complete areola necrosis was 2.5%. These rates are comparable to those in
      the literature. CONCLUSION: Using the technique described above, superior pedicle
      can be applied to all gigantomastia cases and enhanced aesthetic results can be
      obtained with minimal complications. LEVEL OF EVIDENCE V: This journal requires
      that authors assign a level of evidence to each article. For a full description
      of these Evidence-Based Medicine ratings, please refer to the Table of Contents
      or the online Instructions to Authors www.springer.com/00266 .

PMID- 29340750
TI  - A Pilot Study Evaluating the Efficacy and Safety of ARTISS Human Fibrin Sealant
      in External Rhinoplasty.
AB  - BACKGROUND: Fibrin sealant application in rhytidectomy has previously
      demonstrated a reduction in adverse events and drainage volume. Fibrin sealant
      offers multiple potential benefits including decreasing downtime, reducing
      complication rates, and improving patient satisfaction. In this study, we
      evaluated the efficacy and safety of ARTISS [fibrin sealant (human)] in external
      rhinoplasty. METHODS: Nine healthy participants between the ages of 18 and 50
      seeking external rhinoplasty completed this study. All subjects were randomized
      into control and treatment groups and then underwent external rhinoplasty, with
      only the treatment group receiving ARTISS [fibrin sealant (Human)] during
      surgery. Photographs were taken before surgery and 1 day, 1 week, 1 month, 3
      months and 6 months after surgery and used in a blinded assessment of recovery
      time and esthetic improvement with ecchymosis and satisfaction scales. Subject
      recovery time, downtime, and self-esteem were evaluated at 1 day, 1 week, 1 month
      and 6 months after surgery. Recovery time was determined by live assessment of
      edema and ecchymosis using categorical scales. Subject downtime was assessed
      through a 30-day patient diary and a downtime questionnaire. Subject self-esteem
      was evaluated with the Heatherton & Polivy State Self-Esteem Scale. The degree of
      technical ease with the product was determined by the treating investigator with
      a 10-cm Visual Analog Scale. RESULTS: Patients treated with ARTISS intra
      operatively reported significantly higher self-esteem 1 month and 6 months
      following external rhinoplasty. The ARTISS EasysprayTM Spray Set was rated as
      technically easy to administer. CONCLUSION: The use of ARTISS fibrin sealant in
      external rhinoplasties is a safe and easy method and may enhance patient self
      esteem. Larger studies are warranted to either verify or challenge the validity
      of our findings. 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- 29340748
TI  - Lack of level I evidence on how to prevent infection after elective shoulder
      surgery.
AB  - PURPOSE: Infection is a concern after all orthopedic procedures, including
      shoulder surgery. This systematic review of literature aimed to determine risk
      factors for infection as well as the availability and effectiveness of measures
      utilized to prevent infection after elective shoulder surgery. METHODS: An
      electronic database search was performed using MEDLINE (1950-October 2017),
      EMBASE (1980-October 2017), CINAHL (1982-October 2017), and the Cochrane database
      to identify studies reporting a risk factor or preventive measure for infection
      after shoulder surgery. RESULTS: Fifty-one studies were eligible for inclusion.
      Risk factors identified for infection were male sex, the presence of hair,
      receiving an intra-articular cortisone injection within the 3 months prior to
      surgery, smoking, obesity, and several comorbidities. The only preventive measure
      with level I evidence was for the use of chlorhexidine wipes for cleansing the
      skin in the days prior to surgery and for the use of ChloraPrep or DuraPrep over
      povodine and iodine to prep the skin at the time of surgery. Level II-IV evidence
      was found for other infection prevention methods such as intravenous antibiotic
      prophylaxis. CONCLUSION: There are many risk factors associated with developing
      an infection after elective shoulder surgery. Many preventive measures have been
      described which may decrease the risk of infection; however, most lack a high
      level evidence to support them. The findings of this systematic review are
      clinically relevant as it has been shown that infection after shoulder surgery
      results in poor patient-reported outcomes and pose a significant financial
      burden. As surgeons the goal should be to prevent infections to avoid the
      morbidity for patients and the increased cost for society. LEVEL OF EVIDENCE: IV
      systematic review of literature.

PMID- 29340751
TI  - Correction to: Improving the baking quality of bread wheat by genomic selection
      in early generations.
AB  - Unfortunately, the co-author, Dr. Gungor was missed out in the authorship of
      original publication by mistake and it is updated now.

PMID- 29340752
TI  - The effect of INDEHISCENT point mutations on silique shatter resistance in
      oilseed rape (Brassica napus).
AB  - KEY MESSAGE: This study elucidates the influence of indehiscent mutations on
      rapeseed silique shatter resistance. A phenotype with enlarged replum-valve joint
      area and altered cell dimensions in the dehiscence zone is described. Silique
      shattering is a major factor reducing the yield stability of oilseed rape
      (Brassica napus). Attempts to improve shatter resistance often include the use of
      mutations in target genes identified from Arabidopsis (Arabidopsis thaliana). A
      variety of phenotyping methods assessing the level of shatter resistance were
      previously described. However, a comparative and comprehensive evaluation of the
      methods has not yet been undertaken. We verified the increase of shatter
      resistance in indehiscent double knock-down mutants obtained by TILLING with a
      systematic approach comparing three independent phenotyping methods. A positive
      correlation of silique length and shatter resistance was observed and accounted
      for in the analyses. Microscopic studies ruled out the influence of different
      lignification patterns. Instead, we propose a model to explain increased
      shattering resistance of indehiscent rapeseed mutants by altered cell shapes and
      sizes within the contact surfaces of replum and valves.

PMID- 29340753
TI  - Can spelt wheat be used as heterotic group for hybrid wheat breeding?
AB  - KEY MESSAGE: Spelt wheat is a distinct genetic group to elite bread wheat, but
      heterosis for yield and protein quality is too low for spelt to be recommended as
      heterotic group for hybrid breeding in wheat. The feasibility to switch from line
      to hybrid breeding is currently a hot topic in the wheat community. One
      limitation seems to be the lack of divergent heterotic groups within wheat
      adapted to a certain region. Spelt wheat is a hexaploid wheat that can easily be
      crossed with bread wheat and that forms a divergent genetic group when compared
      to elite bread wheat. The aim of this study was to investigate the potential of
      Central European spelt as a heterotic group for Central European bread wheat. We
      performed two large experimental field studies comprising in total 43 spelt
      lines, 14 wheat lines, and 273 wheat-spelt hybrids, and determined yield, heading
      time, plant height, resistance against yellow rust, leaf rust, and powdery
      mildew, as well as protein content and sedimentation volume. Heterosis of yield
      was found to be lower than that of hybrids made between elite wheat lines.
      Moreover, heterosis of the quality trait sedimentation volume was negative.
      Consequently, spelt wheat does not appear suited to be used as heterotic group in
      hybrid wheat breeding. Nevertheless, high combining abilities of a few spelt
      lines with elite bread wheat lines make them interesting resources for pre
      breeding in bread wheat. Thereby, the low correlation between line per se
      performance and combining ability of these spelt lines shows the potential to
      unravel the breeding value of genetic resources by crossing them to an elite
      tester.

PMID- 29340754
TI  - Preoperative evaluation of cochlear implantation through the round window
      membrane in the facial recess using high-resolution computed tomography.
AB  - PURPOSE: We evaluated the risk of cochlear implantation through the round window
      membrane in the facial recess through a preoperative analysis of the angle
      between the facial nerve-round window and the cranial midline using high
      resolution temporal bone CT. METHODS: Temporal bone CT films of 176 patients with
      profound sensorineural hearing loss at our hospital from 2013 to 2015 were
      reviewed. The preoperative temporal bone CT scans of the patients were
      retrospectively analysed. The vertical distance (d value) from the leading edge
      of the facial nerve to the posterior wall of the external auditory canal and the
      angle (alpha value) between the line from the leading edge of the facial nerve to
      the midpoint of the round window membrane and the median sagittal line on the
      round window membrane plane were measured. Based on intraoperative observation,
      the round window membrane was divided into complete round window membrane
      exposure (group A), partial exposure (group B), and unexposed (group C) groups,
      and statistical analysis was performed. RESULTS: The alpha value could be
      effectively measured for all 176 patients (62.60 +/- 7.12), and the d value could
      be effectively measured for 95 cases (5.53 +/- 1.00). An analysis of the
      correlation between the alpha and d values of these 95 cases found a negative
      correlation. Of the 176 cases, one-way analysis of variance (ANOVA) showed that
      the differences among the groups were significant [P = 0.000 (< 0.05)].
      CONCLUSION: The angle (alpha value) between the line connecting the leading edge
      of the facial nerve to the midpoint of the round window and the median sagittal
      line measured in preoperative CT scans was associated with the difficulty of
      intraoperatively exposing the round window membrane. When the alpha value was
      larger than a certain degree, the difficulty of exposing the round window
      membrane was increased. In such cases, the surgeon should fully expose the round
      window membrane during surgery, which could result decrease the likelihood of
      complications.

PMID- 29340755
TI  - Multiple invasion speeds in a two-species integro-difference competition model.
AB  - We study an integro-difference competition model for the case that two species
      consecutively invade a habitat. We show that if a species spreads into a
      traveling wave of its rival, or if two species expand their spatial ranges in
      both directions, in a direction where open space is available, the species with
      larger invasion speed can always establish a wave moving into open space with its
      own speed. We demonstrate that when one species is stronger in competition, under
      appropriate conditions, the speeds at which the boundaries between two species
      move can be analytically determined. We find that in general there are multiple
      invasion speeds in the model. It is possible for a species to develop two
      separate waves propagating with different invasion speeds. It is also possible
      for each species to establish a single wave spreading with distinct speeds in
      both directions. The mathematical analysis relies on linear determinacy and new
      techniques developed.

PMID- 29340756
TI  - Differential effect of a patient-education transition intervention in adolescents
      with IBD vs. diabetes.
AB  - : Patient education programs (PEPs) to improve disease management are part of
      standard and regular treatment in adolescents with diabetes. In Germany, youth
      with inflammatory bowel disease (IBD) receive individual counseling but not PEPs
      in group settings. Generic PEPs have been developed in order to improve
      transition from child-centered to adolescent health services. The aim of the
      study was to investigate the effects of a transition-oriented PEP on quality of
      life (QoL) and self-management in young patients with IBD (PEP naive), compared
      to patients with diabetes (familiar with PEPs). A 2-day transition workshop was
      oriented at improving psychosocial skills and addressed both generic as well as
      specific aspects of the condition. A controlled trial on the outcomes of a
      generic transition-oriented PEP was conducted in 14- to 20-year-old patients with
      IBD (n = 99) and diabetes (n = 153). Transition competence and QoL were assessed
      at baseline and 6-month follow-up. Results show that the intervention lead to a
      significant increase in QoL only in patients with IBD. The PEP significantly
      improved transition competence in both groups, however to a higher extent in
      subjects with IBD. CONCLUSION: Transition-oriented PEPs can have differential
      effects in different patient groups. However, this needs further longitudinal
      investigations. What is Known: * To date, evidence has accumulated concerning the
      effectiveness of patient education programs (PEPs) in pediatric health care for
      chronic conditions such as type 1 diabetes, asthma, atopic dermatitis, or obesity
      but is less documented in inflammatory bowel disease (IBD). In particular, PEPs
      in the transition period have not been investigated in youth with IBD. * The
      current study focuses on evaluating a PEP for transition preparation and
      management designed to be generically used across different chronic conditions
      since many aspects of managing chronic conditions share commonalities across
      conditions. The 2-day workshop included condition-specific modules adapted to the
      specific medical needs but was otherwise similar in quality and organization
      among different conditions. What is New: * The transition-oriented PEP was
      effective in enhancing self-management and transition management skills in both
      patients with IBD and diabetes; however, effects were higher in youth with IBD. A
      significant impact of the intervention on patients' QoL compared to the control
      group was only identified in youth with IBD. * We recommend that patients with
      IBD have access to PEP as a standard treatment as well as to a transition program
      during the course of illness.

PMID- 29340757
TI  - Comparing brain activity patterns during spontaneous exploratory and cue
      instructed learning using single photon-emission computed tomography (SPECT)
      imaging of regional cerebral blood flow in freely behaving rats.
AB  - Learning can be categorized into cue-instructed and spontaneous learning types;
      however, so far, there is no detailed comparative analysis of specific brain
      pathways involved in these learning types. The aim of this study was to compare
      brain activity patterns during these learning tasks using the in vivo imaging
      technique of single photon-emission computed tomography (SPECT) of regional
      cerebral blood flow (rCBF). During spontaneous exploratory learning, higher
      levels of rCBF compared to cue-instructed learning were observed in motor control
      regions, including specific subregions of the motor cortex and the striatum, as
      well as in regions of sensory pathways including olfactory, somatosensory, and
      visual modalities. In addition, elevated activity was found in limbic areas,
      including specific subregions of the hippocampal formation, the amygdala, and the
      insula. The main difference between the two learning paradigms analyzed in this
      study was the higher rCBF observed in prefrontal cortical regions during cue
      instructed learning when compared to spontaneous learning. Higher rCBF during cue
      instructed learning was also observed in the anterior insular cortex and in
      limbic areas, including the ectorhinal and entorhinal cortexes, subregions of the
      hippocampus, subnuclei of the amygdala, and the septum. Many of the rCBF changes
      showed hemispheric lateralization. Taken together, our study is the first to
      compare partly lateralized brain activity patterns during two different types of
      learning.

PMID- 29340758
TI  - Plants eavesdrop on cues produced by snails and induce costly defenses that
      affect insect herbivores.
AB  - Although induced defenses are widespread in plants, the degree to which plants
      respond to herbivore kairomones (incidental chemicals that herbivores produce
      independent of herbivory), the costs and benefits of responding to cues of
      herbivory risk, and the ecological consequences of induced defenses remain
      unclear. We demonstrate that undamaged tomatoes, Solanum lycopersicum, induce
      defenses in response to a kairomone (locomotion mucus) of snail herbivores (Helix
      aspersa). Induced defense had significant costs and benefits for plants: plants
      exposed to snail mucus or a standard defense elicitor (methyl jasmonate, MeJA)
      exhibited slower growth, but also experienced less herbivory by an insect
      herbivore (Spodoptera exigua). We also find that kairomones from molluscan
      herbivores lead to deleterious effects on insect herbivores mediated through
      changes in plant defense, i.e., mucus-induced defenses of Solanum lycopersicum
      reduced growth of S. exigua. These results suggest that incidental cues of
      widespread generalist herbivores might be a mechanism creating variation in plant
      growth, plant defense, and biotic interactions.

PMID- 29340759
TI  - Cecum ulcer is a reliable endoscopic finding in cytomegalovirus colitis
      concomitant with graft-versus-host disease after allogeneic hematopoietic stem
      cell transplantation.
AB  - Although graft-versus-host disease (GVHD) is the major complication of allogeneic
      hematopoietic stem cell transplantation (allo-HSCT), cytomegalovirus (CMV)
      reactivation also occurs in patients after allo-HSCT and these conditions often
      clinically overlap. The aim of this study was to determine reliable endoscopic
      findings of CMV colitis in patients with gastrointestinal graft-versus-host
      disease (GI-GVHD). Patients after allo-HSCT who were histologically confirmed to
      have GI-GVHD with or without CMV colitis and patients with an immunosuppressive
      condition were retrospectively analyzed. We divided the patients into three
      groups: GI-GVHD with CMV colitis (group A), GI-GVHD without CMV colitis (group
      B), and CMV colitis without undergoing allo-HSCT (group C). From medical records,
      the involved colorectal areas and endoscopic findings according to the groups
      were compared. A total of 70 patients were divided into three groups (group A: n
      = 19, group B: n = 28, group C: n = 23). Mucosal injuries in groups A and C
      frequently occurred in the cecum including ileocecal valves. On the other hand,
      there were no abnormal lesions on ileocecal valves in group B. Furthermore, ulcer
      lesions were more frequently observed in groups A and C than in group B (p <
      0.001). The sensitivity and specificity of mucosal injuries in the cecum for
      prediction of CMV colitis were 89.5 and 76.5%, respectively, and mucosal injuries
      in the cecum were more reliable findings than CMV antigenemia. Ulcer lesions in
      the cecum are reliable endoscopic findings for CMV colitis in patients with GI
      GVHD after allo-HSCT.

PMID- 29340760
TI  - Infections associated with ruxolitinib: study in the French Pharmacovigilance
      database.

PMID- 29340761
TI  - Long-term efficacy and toxicity of rituximab plus fludarabine and mitoxantrone (R
      FM) for gastric marginal zone lymphoma: a single-center experience and literature
      review.
AB  - There is no consensus about the best treatment option for patients with HP
      negative gastric MALT lymphomas or persistent disease after HP eradication.We
      have investigated fludarabine and mitoxantrone with rituximab (R-FM) as first
      line treatment. A cohort of 13 patients was analyzed. Induction treatment
      consisted of fludarabine (25 mg/m2 i.v. on days 2 to 4), mitoxantrone (10 mg/m2
      i.v. on day 2), and rituximab (375 mg/m2 i.v. on day 1), for up to six cycles
      every 28 days. All patients achieved a complete remission, a median of four
      cycles was given. Treatment-related toxicities were mainly hematologic, with
      grade 3-4 neutropenia observed in 11/13 patients (84.6%). One patient had grade 3
      febrile neutropenia, two patients developed prolonged pancytopenia (15%), and one
      patient experienced CMV reactivation at 2 months. After a median follow-up of 84
      months, 1/13 had disease relapse and received total gastrectomy; estimated 10
      year progression-free survival and overall survival were 92.4 and 100%,
      respectively. Our study suggests R-FM regimen has a high long-term efficacy for
      untreated HP-negative gastric MALT lymphoma patients and HP-positive patients who
      failed HP eradication. The elevated incidence of grade 3-4 hematological
      toxicity, yet manageable, makes this treatment less safe compared to rituximab in
      combination with chlorambucil or bendamustine.

PMID- 29340762
TI  - The role of endoscopy in the treatment of hydrocephalus associated with
      aneurysmal malformation of the vein of Galen.

PMID- 29340763
TI  - The retinal projection to the nucleus lentiformis mesencephali in zebra finch
      (Taeniopygia guttata) and Anna's hummingbird (Calypte anna).
AB  - In birds, the nucleus of the basal optic root (nBOR) and the nucleus lentiformis
      mesencephali (LM) are retinal recipient nuclei involved in the analysis of optic
      flow and the generation of the optokinetic response. In both pigeons and
      chickens, retinal inputs to the nBOR arise from displaced ganglion cells (DGCs),
      which are found at the margin of the inner nuclear and inner plexiform layers.
      The LM receives afferents from retinal ganglion cells, but whether DGCs also
      project to LM is a matter of debate. Previous work in chickens had concluded that
      DGCs do not project to LM, but a recent study in pigeons found that both retinal
      ganglion cells and DGCs project to LM. These findings leave open the question of
      whether there are species differences with respect to the DGC projection to LM.
      In the present study, we made small injections of retrograde tracer into the LM
      in a zebra finch and an Anna's hummingbird. In both cases, retrogradely labeled
      retinal ganglion cells and DGCs were observed. These results suggest that a
      retinal input to the LM arising from DGCs is characteristic of most, if not all,
      birds.

PMID- 29340764
TI  - Correction to: Population data of 21 autosomal STR loci in the Hausa, Igbo and
      Yoruba people of Nigeria.
AB  - In the original paper author Alani Sulaimon Akanmu was erroneously omitted from
      the author list. Prof. Akanmu has now been added as 4th author. Prof. Akanmu
      acted as an academic supervisor of the study and additionally contributed to the
      publication by reading, commenting and editing the manuscript.

PMID- 29340765
TI  - Orotracheal tube as a risk factor for lower respiratory tract infection:
      preliminary data from a randomised trial.
AB  - PURPOSE: The aim of the study was to investigate whether polyurethane (PU)
      endotracheal tubes, continuous measurements of cuff pressure and aspiration of
      the subglottic space as a bundle of parameters could reduce patients' risk for
      developing ventilator associated pneumonia (VAP). METHODS: Two groups of patients
      that differed only in terms of endotracheal tubes and intubation intervention
      were compared. Group A was ventilated using PU tubes a with conical cuff; they
      also had continuous cuff pressure measurement and continuous subglottic
      aspiration. Group B was ventilated using PVC tubes with a cylindrical cuff; the
      patients underwent intermittent cuff pressure measurement and intermittent
      subglottic aspiration. RESULTS: Seven patients in group A (13.2%) and 18 in group
      B (36.0%) out of 103 were diagnosed with VAP. VAP patients were in general older,
      stayed longer in the ICU and were ventilated significantly longer compared with
      the patients with no VAP. Eight more patients in group B died compared with group
      A. Moreover, subjects in group A survived longer. Patient age, hours on
      mechanical ventilation, and days on an ICU were all positively associated with
      the occurrence of VAP. CONCLUSIONS: Prevention parameters in ventilation (PU
      cuff, conical cuff, continuous subglottic drainage and continuous cuff pressure
      measurement) could prevent the incidence of VAP in ICU patients.

PMID- 29340766
TI  - Wanted: a better cut-off value for the Epworth Sleepiness Scale.
AB  - BACKGROUND: Excessive daytime sleepiness (EDS) is the main complaint in many
      neurological sleep disorders, such as idiopathic hypersomnia, narcolepsy, or
      obstructive sleep apnea/hypopnea syndrome (OSAS). The validity of the Epworth
      Sleepiness Scale (ESS) as a screening tool for EDS remains controversial. We
      therefore investigated (1) the interrelation of the ESS total score and the mean
      sleep latency (MSL) during the multiple sleep latency test (MSLT) and (2) the
      diagnostic accuracy of the ESS total score to detect EDS in patients with the
      chief complaint of subjective EDS. METHODS: A total of 94 patients (48 males)
      with subjective EDS were included in this study. Regression analyses and ROC
      curve analyses were carried out to assess the predictive value of the ESS score
      for MSL. RESULTS: The ESS score significantly predicted a shortened MSL (p =
      0.01, beta = -0.29). After dichotomizing into two groups, the ESS score predicted
      MSL only in patients with hypersomnia or narcolepsy (p = 0.01, beta = -0.33), but
      not in patients with other clinical diagnoses (e. g. OSAS; p = 0.36, beta = 
      0.15). The ROC curve analyses indicated an optimal ESS cut-off value of 16 with a
      sensitivity of 70%; however, specificity remained unsatisfactory (55.6%).
      CONCLUSIONS: Our results suggest that the predictive value of the ESS score in
      patients with subjective EDS is low and patient subgroup-specific (superior in
      hypersomnia/narcolepsy vs. other diagnoses) and that the commonly used cut-off of
      11 points may be insufficient for clinical practice.

PMID- 29340767
TI  - Analysis of prognostic factors after resection of solitary liver metastasis in
      colorectal cancer: a 22-year bicentre study.
AB  - PURPOSE: The investigation of the predictors of outcome after hepatic resection
      for solitary colorectal liver metastasis. METHODS: We recruited 350 patients with
      solitary colorectal liver metastasis at the University Hospitals of Jena and
      Magdeburg, who underwent curative liver resection between 1993 and 2014. All
      patients had follow-up until death or till summer 2016. RESULTS: The follow-up
      data concern 96.6% of observed patients. The 5- and 10-year overall survival
      rates were 47 and 28%, respectively. The 5- and 10-year disease-free survival
      rates were 30 and 20%, respectively. The analysis of the prognostic factors
      revealed that the pT category of primary tumour, size and grade of the metastasis
      and extension of the liver resection had no statistically significant impact on
      survival and recurrence rates. In multivariate analysis, age, status of lymph
      node metastasis at the primary tumour, location of primary tumour, time of
      appearance of the metastasis, the use of preoperative chemotherapy and the
      presence of extrahepatic tumour proved to be independent statistically
      significant predictors for the prognosis. Moreover, patients with rectal cancer
      had a lower intrahepatic recurrence rate, but a higher extrahepatic recurrence
      rate. CONCLUSION: The long-term follow-up of patients with R0-resected liver
      metastasis is multifactorially influenced. Age and comorbidity have a role only
      in the overall survival. More than three lymph node metastasis reduced both the
      overall and disease-free survival. Extrahepatic tumour had a negative influence
      on the extrahepatic recurrence and on the overall survival. Neither overall
      survival nor recurrence rates was improved using neoadjuvant chemotherapy.

PMID- 29340770
TI  - [A fresh look at the German Survey on Aging].

PMID- 29340768
TI  - The comparison of clinical outcomes in patients with acute myocardial infarction
      and advanced chronic kidney disease on chronic hemodialysis versus off
      hemodialysis.
AB  - Acute myocardial infarction (AMI) is more frequently observed in patients with
      chronic kidney disease (CKD) than in patients without CKD. Initial treatment
      strategy for AMI includes primary percutaneous coronary intervention (PCI), which
      requires substantial amount of contrast media. We hypothesized that the clinical
      outcomes are comparable or worse in patients with AMI and advanced CKD off
      chronic hemodialysis as compared to patients with AMI and advanced CKD on chronic
      hemodialysis. The purpose of this study was to compare the clinical outcomes of
      patients with AMI and advanced CKD on hemodialysis versus off hemodialysis. A
      total of 148 patients with estimated glomerular filtration rate < 30 ml/min/1.73
      m2 on admission were included and were divided into the HD group (n = 68) and non
      HD group (n = 80). The length of hospitalization was significantly less in the HD
      group (15.7 +/- 14.8 days) than in the non-HD group (22.4 +/- 21.3 days) (P =
      0.01). In-hospital death was significantly less in the HD group (10.3%) than in
      the non-HD group (25.0%) (P = 0.02). While the non-HD group was not significantly
      associated with in-hospital death after controlling clinical covariates, the non
      HD group (odd ratio 2.89, 95% confidence interval 1.03-8.12, P = 0.04) was
      significantly associated with long hospitalization even after controlling
      clinical covariates. In conclusion, as compared to advanced CKD on chronic
      hemodialysis, advanced CKD off hemodialysis had higher morbidity and mortality in
      patients with AMI. Advanced CKD off hemodialysis was closely associated with long
      hospitalization even after controlling clinical factors.

PMID- 29340772
TI  - The influence of passionate love on self-other discrimination during joint
      action.
AB  - Prior research on romantic relationships suggests that being in love involves a
      blurring of self-other cognitive boundaries. However, this research has focused
      so far on conceptual self-representation, related to the individual's traits or
      interests. The present study tested the hypothesis that passionate love involves
      a reduced discrimination between the self and the romantic partner at a bodily
      level, as indexed by an increased Joint Simon effect (JSE), and we further
      examined whether this self-other discrimination correlated with the passion felt
      for the partner. As predicted, we found an increased JSE when participants
      performed the Joint Simon Task with their romantic partner compared with a friend
      of the opposite sex. Providing support for the self-expansion model of love (Aron
      and Aron in Pers Relatsh 3(1):45-58, 1996), this result indicates that romantic
      relationships blur the boundaries between the self and the romantic partner at a
      bodily level. Furthermore, the strength of romantic feelings was positively
      correlated with the magnitude of the JSE when sharing the task with the romantic
      partner.

PMID- 29340771
TI  - Predictive factors for pharyngocutaneous fistulization after total laryngectomy:
      a Dutch Head and Neck Society audit.
AB  - BACKGROUND: Incidences of pharyngocutaneous fistulization (PCF) after total
      laryngectomy (TL) reported in the literature vary widely, ranging from 2.6 to
      65.5%. Comparison between different centers might identify risk factors, but also
      might enable improvements in quality of care. To enable this on a national level,
      an audit in the 8 principle Dutch Head and Neck Centers (DHNC) was initiated.
      METHODS: A retrospective chart review of all 324 patients undergoing laryngectomy
      in a 2-year (2012 and 2013) period was performed. Overall PCF%, PCF% per center
      and factors predictive for PCF were identified. Furthermore, a prognostic model
      predicting the PCF% per center was developed. To provide additional data, a
      survey among the head and neck surgeons of the participating centers was carried
      out. RESULTS: Overall PCF% was 25.9. The multivariable prediction model revealed
      that previous treatment with (chemo)radiotherapy in combination with a long
      interval between primary treatment and TL, previous tracheotomy, near total
      pharyngectomy, neck dissection, and BMI < 18 were the best predictors for PCF.
      Early oral intake did not influence PCF rate. PCF% varied quite widely between
      centers, but for a large extend this could be explained with the prediction
      model. PCF performance rate (difference between the PCF% and the predicted PCF%)
      per DHNC, though, shows that not all differences are explained by factors
      established in the prediction model. However, these factors explain enough of the
      differences that, compensating for these factors, hospital is no longer
      independently predictive for PCF. CONCLUSIONS: This nationwide audit has provided
      valid comparative PCF data confirming the known risk factors from the literature
      which are important for counseling on PCF risks. Data show that variations in
      PCF% in the DHNCs (in part) are explainable by the variations in these predictive
      factors. Since elective neck dissection is a major risk factor for PCF, it only
      should be performed on well funded indication.

PMID- 29340773
TI  - Feature codes in implicit sequence learning: perceived stimulus locations
      transfer to motor response locations.
AB  - An important question in implicit sequence learning research is how the learned
      information is represented. In earlier models, the representations underlying
      implicit learning were viewed as being either purely motor or perceptual. These
      different conceptions were later integrated by multidimensional models such as
      the Dual System Model of Keele et al. (Psychol Rev 110(2):316-339, 2003).
      According to this model, different types of sequential information can be learned
      in parallel, as long as each sequence comprised only one single dimension (e.g.,
      shapes, colors, or response locations). The term dimension, though, is
      underspecified as it remains an open question whether the involved learning
      modules are restricted to motor or to perceptual information. This study aims to
      show that the modules of the implicit learning system are not specific to motor
      or perceptual processing. Rather, each module processes an abstract feature code
      which represents both response- and perception-related information. In two
      experiments, we showed that perceiving a stimulus-location sequence transferred
      to a motor response-location sequence. This result shows that the mere perception
      of a sequential feature automatically leads to an activation of the respective
      motor feature, supporting the notion of abstract feature codes being the basic
      modules of the implicit learning system. This result could only be obtained,
      though, when the task instructions emphasized the encoding of the stimulus
      locations as opposed to an encoding of the color features. This limitation will
      be discussed taking into account the importance of the instructed task set.

PMID- 29340774
TI  - 'Exercise to me is a scary word': perceptions of fatigue, sleep dysfunction, and
      exercise in people with fibromyalgia syndrome-a focus group study.
AB  - Fibromyalgia syndrome (FMS) is a common and complex chronic pain condition.
      Exercise is recommended in the management of the FMS; however, people with FMS
      often find exercise exacerbates their condition and causes overwhelming fatigue.
      The objective of this study was to explore the perceptions of fatigue and sleep
      dysfunction, and exercise in people with FMS. Three, 60-90 min focus groups were
      conducted with people with FMS (n = 14). Participants were recruited from patient
      support groups who had experienced therapeutic exercise in the management of
      their condition. Focus groups were video and audio recorded and transcriptions
      analysed for thematic content by three independent evaluators. Fatigue, sleep
      dysfunction, and pain were universally reported by participants. The over-arching
      theme to emerge was a lack of understanding of the condition by others. A huge
      sense of loss was a major sub-theme and participants felt that they had
      fundamentally changed since the onset of FMS. Participants reported that they
      were unable to carry out their normal activities, including physical activity and
      exercise. The invisibility of FMS was associated with the lack of understanding
      by others, the sense of loss, and the impact of FMS. People with FMS perceive
      that there is a lack of understanding of the condition among health care
      professionals and the wider society. Those with FMS expressed a profound sense of
      loss of their former 'self'; part of this loss was the ability to engage in
      normal physical activity and exercise.

PMID- 29340776
TI  - Ectopic Cushing's syndrome secondary to olfactory neuroblastoma.
AB  - We present the case of a patient with Cushing's syndrome secondary to ectopic
      ACTH secretion. A MR of the head showed a left-sided nasal mass extending down
      from the cribriform plate. The patient underwent endoscopic resection with nearly
      complete removal of the mass. Histological examination showed an ACTH-secreting
      olfactory neuroblastoma (ONB). The patient's cortisol levels returned to normal
      range after surgery and have remained normal for over a year. ONB is a rare cause
      for ectopic ACTH secretion. This case highlights the diagnostic and management
      difficulties in patients with ectopic ACTH secretion, and provides a brief review
      of ONB.

PMID- 29340775
TI  - Global versus local mechanisms of temperature sensing in ion channels.
AB  - Ion channels turn diverse types of inputs, ranging from neurotransmitters to
      physical forces, into electrical signals. Channel responses to ligands generally
      rely on binding to discrete sensor domains that are coupled to the portion of the
      channel responsible for ion permeation. By contrast, sensing physical cues such
      as voltage, pressure, and temperature arises from more varied mechanisms. Voltage
      is commonly sensed by a local, domain-based strategy, whereas the predominant
      paradigm for pressure sensing employs a global response in channel structure to
      membrane tension changes. Temperature sensing has been the most challenging
      response to understand and whether discrete sensor domains exist for pressure and
      temperature has been the subject of much investigation and debate. Recent
      exciting advances have uncovered discrete sensor modules for pressure and
      temperature in force-sensitive and thermal-sensitive ion channels, respectively.
      In particular, characterization of bacterial voltage-gated sodium channel
      (BacNaV) thermal responses has identified a coiled-coil thermosensor that
      controls channel function through a temperature-dependent unfolding event. This
      coiled-coil thermosensor blueprint recurs in other temperature sensitive ion
      channels and thermosensitive proteins. Together with the identification of ion
      channel pressure sensing domains, these examples demonstrate that "local" domain
      based solutions for sensing force and temperature exist and highlight the
      diversity of both global and local strategies that channels use to sense physical
      inputs. The modular nature of these newly discovered physical signal sensors
      provides opportunities to engineer novel pressure-sensitive and thermosensitive
      proteins and raises new questions about how such modular sensors may have evolved
      and empowered ion channel pores with new sensibilities.

PMID- 29340777
TI  - Answer to the Letter to the Editor of Yi Liu et al. concerning "Spinal movement
      and dural sac compression during airway management in a cadaveric model with
      atlanto-occipital instability" by Liao S, Schneider NRE, Weilbacher F et al.
      (2017) Eur Spine J. doi:10.1007/s00586-017-5416-9.

PMID- 29340778
TI  - Successful surgery for a neuromuscular scoliosis patient by pulmonary
      rehabilitation with forced vital capacity below 30.
AB  - A rare case of a 15-year-old male patient with neuromuscular scoliosis with
      forced vital capacity (FVC) below 30%, who went through a successful surgery
      without any pulmonary complications, is reported herein. The patient had obvious
      asymmetric shoulders and poor exercise tolerance. The Cobb's angle of the main
      thoracic curve was 62.8 degrees , and FVC in sitting position was 18% of
      predictive value. After skull traction and pulmonary rehabilitation, the FVC was
      still below 30%, and he finally went through surgery under this serious
      condition. By early pulmonary rehabilitation using home ventilator, he
      successfully recovered without any pulmonary complications. The patient had
      complete symptom remission and no deterioration of Cobb's angle was found during
      follow-up.

PMID- 29340779
TI  - Dose, image quality and spine modeling assessment of biplanar EOS micro-dose
      radiographs for the follow-up of in-brace adolescent idiopathic scoliosis
      patients.
AB  - PURPOSE: The aim of this study was to compare the radiation dose, image quality
      and 3D spine parameter measurements of EOS low-dose and micro-dose protocols for
      in-brace adolescent idiopathic scoliosis (AIS) patients. METHODS: We
      prospectively included 25 consecutive patients (20 females, 5 males) followed for
      AIS and undergoing brace treatment. The mean age was 12 years (SD 2 years, range
      8-15 years). For each patient, in-brace biplanar EOS radiographs were acquired in
      a standing position using both the conventional low-dose and micro-dose
      protocols. Dose area product (DAP) was systematically recorded. Diagnostic image
      quality was qualitatively assessed by two radiologists for visibility of
      anatomical structures. The reliability of 3D spine modeling between two operators
      was quantitatively evaluated for the most clinically relevant 3D radiological
      parameters using intraclass correlation coefficient (ICC). RESULTS: The mean DAP
      for the posteroanterior and lateral acquisitions was 300 +/- 134 and 433 +/- 181
      mGy cm2 for the low-dose radiographs, and 41 +/- 19 and 81 +/- 39 mGy cm2 for
      micro-dose radiographs. Image quality was lower with the micro-dose protocol. The
      agreement was "good" to "very good" for all measured clinical parameters when
      comparing the low-dose and micro-dose protocols (ICC > 0.73). CONCLUSION: The
      micro-dose protocol substantially reduced the delivered dose (by a factor of 5-7
      compared to the low-dose protocol) in braced children with AIS. Although image
      quality was reduced, the micro-dose protocol proved to be adapted to radiological
      follow-up, with adequate image quality and reliable clinical measurements. These
      slides can be retrieved under Electronic Supplementary Material.

PMID- 29340780
TI  - Health-related quality of life in outpatients with schizophrenia: factors that
      determine changes over time.
AB  - PURPOSE: The objective of this study was to analyze the clinical factors
      associated with changes in HRQoL in outpatients with schizophrenia using both
      generic and condition-specific HRQoL scales. METHODS: Adult outpatients with
      schizophrenia at least 18 years of age who did not have an acute psychotic
      exacerbation in the 3 months prior to baseline were recruited. PANSS dimensions
      were calculated based on Lindenmayer et al.'s five factors. HRQoL data were
      assessed by patients using the Schizophrenia Quality of Life Scale (SQLS), the
      Short Form-36 (SF-36), and the EuroQol-5 Dimension (EQ-5D) questionnaires.
      RESULTS: Out of the 1345 patients included at baseline, 1196 (89%) were evaluated
      at 12 months. Regression models showed that the factor most consistently
      associated with HRQoL at endpoint was change in the PANSS negative symptoms
      score. A decrease in the PANSS negative symptoms score from baseline to 1 year
      was associated with a decrease in HRQoL during the same period. There were also
      significant associations of the change in PANSS excitatory factor with all the
      HRQoL scales except the SF-36 PCS. Female gender was associated with a decrease
      in all HRQoL ratings. There was also a relationship between years since onset and
      HRQoL. The longer the time since illness onset, the larger the decrease in HRQoL.
      CONCLUSIONS: This study has found that, in outpatients with schizophrenia,
      changes in negative and excitement symptoms may have a greater an association
      with HRQoL than changes in positive, cognitive and depressive symptoms.

PMID- 29340782
TI  - Strigeid parasites of Circus buffoni from Argentina, with the description of a
      new species of Parastrigea Szidat, 1928.
AB  - Studying the Helminthological Collection of Museo de La Plata (MLP-He), several
      specimens of digeneans, recovered parasitizing a long-winged harrier, Circus
      buffoni (Accipitridae) from Buenos Aires Argentina, were analysed. The
      morphological and morphometric analysis of these specimens revealed the presence
      of two strigeid species, one of them new for science. Parastrigea buffoni n. sp.
      is characterised by a forebody differentiated in a retractile cephalic region
      with a large opening and a balloon-shaped collar region or collerette, suckers
      located in cephalic region, holdfast organ with well development dorsal and
      ventral lips that can emerge through opening, a claviform hindbody, a large
      copulatory bursa with muscular ring (Ringnapf) and a genital cone well delimited,
      crossed by a sinuous hermaphroditic duct with internal rugae. The euryxenous
      parasite, Strigea falconis brasiliana, is briefly described, parasitizing a new
      host. This is the first record of helminths parasitizing long-winged harrier.

PMID- 29340781
TI  - Suicidal thoughts and behaviors among college students and same-aged peers:
      results from the World Health Organization World Mental Health Surveys.
AB  - PURPOSE: The primary aims are to (1) obtain representative prevalence estimates
      of suicidal thoughts and behaviors (STB) among college students worldwide and (2)
      investigate whether STB is related to matriculation to and attrition from
      college. METHODS: Data from the WHO World Mental Health Surveys were analyzed,
      which include face-to-face interviews with 5750 young adults aged 18-22 spanning
      21 countries (weighted mean response rate = 71.4%). Standardized STB prevalence
      estimates were calculated for four well-defined groups of same-aged peers:
      college students, college attriters (i.e., dropouts), secondary school graduates
      who never entered college, and secondary school non-graduates. Logistic
      regression assessed the association between STB and college entrance as well as
      attrition from college. RESULTS: Twelve-month STB in college students was 1.9%, a
      rate significantly lower than same-aged peers not in college (3.4%; OR 0.5; p <
      0.01). Lifetime prevalence of STB with onset prior to age 18 among college
      entrants (i.e., college students or attriters) was 7.2%, a rate significantly
      lower than among non-college attenders (i.e., secondary school graduates or non
      graduates; 8.2%; OR 0.7; p = 0.03). Pre-matriculation onset STB (but not post
      matriculation onset STB) increased the odds of college attrition (OR 1.7; p <
      0.01). CONCLUSION: STB with onset prior to age 18 is associated with reduced
      likelihood of college entrance as well as greater attrition from college. Future
      prospective research should investigate the causality of these associations and
      determine whether targeting onset and persistence of childhood-adolescent onset
      STB leads to improved educational attainment.

PMID- 29340783
TI  - Identification of bat trypanosomes from Minas Gerais state, Brazil, based on 18S
      rDNA and Cathepsin-L-like targets.
AB  - Several bat species can be infected by trypanosomes, but there is not much
      information about which of these parasites infect bats from Triangulo Mineiro and
      Alto Paranaiba, Minas Gerais state, Brazil, a formerly endemic region for
      Trypanosoma cruzi, the causative agent of Chagas disease. The aim of this study
      was to describe, characterize, and identify the presence of trypanosomes in bats.
      The captured bats (448) belong to four families and to 19 different species. Of
      those, 37 bats were found to be positive for trypanosomes by microhematocrit,
      (infection rate 8.3%) and 27 were positive after hemoculture analysis. Initially,
      the isolates were identified by PCR (18S rDNA, 24Salpha rDNA, spliced leader,
      COII RFLP-PCR) using primers originally designed for T. cruzi. PCRs (18S rDNA,
      24Salpha rDNA) showed compatible bands for TcI, whereas COII RFLP-PCR showed a
      similar pattern associated to TcII. However, there was no DNA amplification using
      spliced leader as a target, revealing a discrepancy between the results.
      Phylogenetic analysis of Cathepsin L-like and 18S rDNA sequences proved that 15
      of the isolates corresponded to Trypanosoma cruzi marinkellei and one to
      Trypanosoma dionisii. These results revealed that the diversity of trypanosome
      species in a region considered endemic for Chagas disease is greater than
      previous descriptions. All this can confirm the necessity of using DNA sequencing
      approaches in order to determinate trypanosomes species isolated from bats.

PMID- 29340784
TI  - A new flesh fly species (Diptera: Sarcophagidae) parasitic on leptodactylid
      frogs.
AB  - Here we describe a new species of sarcophagid fly reared from larvae found
      feeding on three species of leptodactylid frogs collected in subtropical
      Corrientes Province in northeastern Argentina. Our species description is based
      on adult male and female external morphology and genitalia. Adult males and
      females of the new species were associated with certainty because all specimens
      studied were reared from single clutches of larvae on each of three infested
      frogs. Thus, adult males and females reared from each clutch were siblings that
      emerged almost simultaneously. The paper provides line drawings, high-resolution
      photographs, and SEM images to aid in identifying Lepidodexia (Notochaeta)
      adelina sp. nov. and to distinguish the new species from its closely related
      congeners. We include brief notes on the host species and on larval feeding
      behavior of L. (N.) adelina. This is the first and only species in the genus
      Lepidodexia reported to parasitize leptodactylid frogs. Further, our observations
      reported here are the first to fully document a completed life cycle by
      sarcophagid fly larvae on three different species of leptodactylid frogs and the
      only well-documented case of myiasis of an amphibian in Argentina.

PMID- 29340785
TI  - Nitric oxide acts downstream of abscisic acid in molybdenum-induced oxidative
      tolerance in wheat.
AB  - KEY MESSAGE: Our study first reveals that Mo mediates oxidative tolerance through
      ABA signaling. Moreover, NO acts downstream of ABA signaling in Mo-induced
      oxidative tolerance in wheat under drought stress. Nitric oxide (NO) is related
      to the improvement of molybdenum (Mo)-induced oxidative tolerance. While the
      function of Mo in abscisic acid (ABA) synthesis and in mediating oxidative
      tolerance by the interaction of ABA and NO remain to be studied. The -Mo and +Mo
      treatment-cultivated wheat was separated and subsequently was pretreated with AO
      inhibitor, ABA synthesis inhibitor, exogenous ABA, NO scavenger, NO donor or
      their combinations under polyethylene glycol 6000 (PEG)-stimulated drought stress
      (PSD). The AO activity and ABA content were increased by Mo in wheat under PSD,
      however, AO inhibitor decreased AO activity, correspondingly reduced ABA
      accumulation, suggesting that AO involves in the regulation of Mo-induced ABA
      synthesis. Mo enhanced activities and expressions of antioxidant enzyme, while
      these effects of Mo were reversed by AO inhibitor and ABA synthesis inhibitor due
      to the decrease of ABA content, but regained by exogenous ABA, indicating that Mo
      induces oxidative tolerance through ABA. Moreover, NO scavenger inhibited
      activities of antioxidant enzyme caused by Mo and exogenous ABA, but the
      inhibitions were eliminated by NO donor, indicating that NO is involved in ABA
      pathway in the regulation of Mo-induced oxidative tolerance in wheat under PSD.
      Finally, we proposed a scheme for the mechanism of Mo-induced oxidative
      tolerance.

PMID- 29340786
TI  - In silico identification and experimental validation of amino acid motifs
      required for the Rho-of-plants GTPase-mediated activation of receptor-like
      cytoplasmic kinases.
AB  - KEY MESSAGE: Several amino acid motifs required for Rop-dependent activity were
      found to form a common surface on RLCKVI_A kinases. This indicates a unique
      mechanism for Rho-type GTPase-mediated kinase activation in plants. Rho-of-plants
      (Rop) G-proteins are implicated in the regulation of various cellular processes,
      including cell growth, cell polarity, hormonal and pathogen responses. Our
      knowledge about the signalling pathways downstream of Rops is continuously
      increasing. However, there are still substantial gaps in this knowledge. One
      reason for this is that these pathways are considerably different from those
      described for yeast and/or animal Rho-type GTPases. Among others, plants lack all
      Rho/Rac/Cdc42-activated kinase families. Only a small group of plant-specific
      receptor-like cytoplasmic kinases (RLCK VI_A) has been shown to exhibit Rop
      binding-dependent in vitro activity. These kinases do not carry any known GTPase
      binding motifs. Based on the sequence comparison of the Rop-activated RLCK VI_A
      and the closely related but constitutively active RLCK VI_B kinases, several
      distinguishing amino acid residues/motifs were identified. All but one of these
      were found to be required for the Rop-mediated regulation of the in vitro
      activity of two RLCK VI_A kinases. Structural modelling indicated that these
      motifs might form a common Rop-binding surface. Based on in silico data mining,
      kinases that have the identified Rop-binding motifs are present in Embryophyta
      but not in unicellular green algae. It can, therefore, be supposed that Rops
      recruited these plant-specific kinases for signalling at an early stage of land
      plant evolution.

PMID- 29340788
TI  - The impact of advanced maternal age on the outcome of twin pregnancies.
AB  - PURPOSE: To assess the effect of advanced maternal age on the obstetrics and
      neonatal outcome of twin pregnancies. METHODS: A retrospective study of 716
      dichorionic-diamniotic twin pregnancies delivered at our institute. The study
      population was divided into two groups: women aged 35-39 years (group A, n = 142)
      and women aged >= 40 years (Group B, n = 48). The control group consisted of
      women younger than 35 years (group C, n = 516). RESULTS: The rate of cesarean
      section (CS) was significantly higher among women older than 35 years compared to
      the control group (A 76.8% and B 87.5% vs C 65.7%, P = 0.001). Women older than
      35 years were also at higher risk for developing hypertensive disorders (A 7.0%,
      B 14.6%, vs C 5.4%, P = 0.04). On multivariate regression analysis, maternal age
      was found to be independently associated with a higher rate of CS (odds ratio vs
      reference group C: group A 1.6, 95% CI 1.08-2.6; group B 3.2, 95% CI 1.3-7.8).
      There was no difference between the groups in the rate of neonatal complications.
      CONCLUSION: Women with twin pregnancy, older than 35 years, have a significantly
      higher rate of CS and hypertensive disorder. This rate increases with maternal
      age, with no increased rate of neonatal complications.

PMID- 29340787
TI  - A profilin gene promoter from switchgrass (Panicum virgatum L.) directs strong
      and specific transgene expression to vascular bundles in rice.
AB  - KEY MESSAGE: A switchgrass vascular tissue-specific promoter (PvPfn2) and its 5'
      end serial deletions drive high levels of vascular bundle transgene expression in
      transgenic rice. Constitutive promoters are widely used for crop genetic
      engineering, which can result in multiple off-target effects, including
      suboptimal growth and epigenetic gene silencing. These problems can be
      potentially avoided using tissue-specific promoters for targeted transgene
      expression. One particularly urgent need for targeted cell wall modification in
      bioenergy crops, such as switchgrass (Panicum virgatum L.), is the development of
      vasculature-active promoters to express cell wall-affective genes only in the
      specific tissues, i.e., xylem and phloem. From a switchgrass expression atlas we
      identified promoter sequence upstream of a vasculature-specific switchgrass
      profilin gene (PvPfn2), especially in roots, nodes and inflorescences. When the
      putative full-length (1715 bp) and 5'-end serial deletions of the PvPfn2 promoter
      (shortest was 413 bp) were used to drive the GUS reporter expression in stably
      transformed rice (Oryza sativa L.), strong vasculature-specificity was observed
      in various tissues including leaves, leaf sheaths, stems, and flowers. The
      promoters were active in both phloem and xylem. It is interesting to note that
      the promoter was active in many more tissues in the heterologous rice system than
      in switchgrass. Surprisingly, all four 5'-end promoter deletions, including the
      shortest fragment, had the same expression patterns as the full-length promoter
      and with no attenuation in GUS expression in rice. These results indicated that
      the PvPfn2 promoter variants are new tools to direct transgene expression
      specifically to vascular tissues in monocots. Of special interest is the very
      compact version of the promoter, which could be of use for vasculature-specific
      genetic engineering in monocots.

PMID- 29340789
TI  - Fully sialylated alpha-chain of complement 4-binding protein (A2160): a novel
      prognostic marker for epithelial ovarian carcinoma.
AB  - PURPOSE: Fully sialylated alpha-chain of complement 4-binding protein (A2160) is
      a member of the glycoprotein family and has recently been identified as a
      diagnostic biomarker for epithelial ovarian cancer. This study examined the
      utility of A2160 as a prognostic biomarker for this disease. METHODS: This is a
      retrospective analysis of prospectively collected plasma samples from 93 women
      with stage I-IV epithelial ovarian cancer who underwent primary cytoreductive
      surgery between 2009 and 2014. Pretreatment A2160 levels were correlated to
      clinico-pathological factors and survival outcome. RESULTS: Women with advanced
      stage disease had significantly higher 2160 levels compared to those with early
      stage disease (stage I-II versus III-IV, median 2.17-2.70 versus 5.31-8.70 U/mL,
      P < 0.01). Women with high-grade serous ovarian carcinoma had higher A2160 levels
      compared to other histologies (6.60 versus 3.01 U/mL, P = 0.05). Women who had
      suboptimal cytoreduction had significantly higher A2160 levels than those who
      achieved optimal/complete cytoreduction (7.02 versus 2.30-3.17 U/mL, P < 0.01).
      On univariable analysis, higher A2160 levels were significantly associated with
      decreased progression-free survival (64-100 versus 1-33%ile, 5-year rates 53.4
      versus 78.9%, P = 0.029). After controlling for age, CA-125 level, cytoreductive
      status, histology, and stage, higher A2160 levels remained an independent
      prognostic factor for decreased progression-free survival (adjusted-hazard ratio
      (HR) 2.48, 95% confidence interval (CI) 1.01-6.11, P = 0.049). Similarly, higher
      A2160 levels were independently associated with decreased cause-specific survival
      on multivariable analysis (adjusted-HR 3.07, 95% CI 1.19-7.93, P = 0.021).
      CONCLUSION: Our study suggests that A2160 may be a useful prognostic biomarker
      for epithelial ovarian cancer, and higher pretreatment levels of A2160 predicts
      poor survival outcome.

PMID- 29340790
TI  - An automated framework for QSAR model building.
AB  - BACKGROUND: In-silico quantitative structure-activity relationship (QSAR) models
      based tools are widely used to screen huge databases of compounds in order to
      determine the biological properties of chemical molecules based on their chemical
      structure. With the passage of time, the exponentially growing amount of
      synthesized and known chemicals data demands computationally efficient automated
      QSAR modeling tools, available to researchers that may lack extensive knowledge
      of machine learning modeling. Thus, a fully automated and advanced modeling
      platform can be an important addition to the QSAR community. RESULTS: In the
      presented workflow the process from data preparation to model building and
      validation has been completely automated. The most critical modeling tasks (data
      curation, data set characteristics evaluation, variable selection and validation)
      that largely influence the performance of QSAR models were focused. It is also
      included the ability to quickly evaluate the feasibility of a given data set to
      be modeled. The developed framework is tested on data sets of thirty different
      problems. The best-optimized feature selection methodology in the developed
      workflow is able to remove 62-99% of all redundant data. On average, about 19% of
      the prediction error was reduced by using feature selection producing an increase
      of 49% in the percentage of variance explained (PVE) compared to models without
      feature selection. Selecting only the models with a modelability score above 0.6,
      average PVE scores were 0.71. A strong correlation was verified between the
      modelability scores and the PVE of the models produced with variable selection.
      CONCLUSIONS: We developed an extendable and highly customizable fully automated
      QSAR modeling framework. This designed workflow does not require any advanced
      parameterization nor depends on users decisions or expertise in machine
      learning/programming. With just a given target or problem, the workflow follows
      an unbiased standard protocol to develop reliable QSAR models by directly
      accessing online manually curated databases or by using private data sets. The
      other distinctive features of the workflow include prior estimation of data
      modelability to avoid time-consuming modeling trials for non modelable data sets,
      an efficient variable selection procedure and the facility of output availability
      at each modeling task for the diverse application and reproduction of historical
      predictions. The results reached on a selection of thirty QSAR problems suggest
      that the approach is capable of building reliable models even for challenging
      problems.

PMID- 29340791
TI  - Treatment of disabling headache with greater occipital nerve injections in a
      large population of childhood and adolescent patients: a service evaluation.
AB  - BACKGROUND: Pediatric headache disorders can be extremely disabling, with marked
      reduction in the quality of life of children and their carers. Evidenced-based
      options for the treatment of primary headache disorders with preventive
      medication is limited and clinical outcomes are often unsatisfactory. Greater
      occipital nerve injections represent a rapid and well-tolerated therapeutic
      option, which is widely used in clinical practice in adults, and has previously
      shown a good outcome in a pediatric population. METHODS: This service evaluation
      reviewed greater occipital nerve injections performed unilaterally with 30 mg 1%
      lidocaine and 40 mg methylprednisolone, to treat disabling headache disorders in
      children and adolescents. RESULTS: We analyzed a total of 159 patients who
      received 380 injections. Of the population, 79% had chronic migraine, 14% new
      daily persistent headache, 4% a trigeminal autonomic cephalalgia, 3% secondary
      headache and one patient had chronic tension-type headache. An improvement after
      injection was seen in 66% (n = 105) of subjects, lasting on average 9 +/- 4
      weeks. Improvement was seen in 68% of patients with chronic migraine, 67% with a
      trigeminal autonomic cephalalgia and 59% with new daily persistent headache. Side
      effects were reported in 8% and were mild and transient. Older age, female
      gender, chronic migraine, increased number of past preventive use, medication
      overuse and developing side effects were all associated with an increased
      likelihood of positive treatment outcome. CONCLUSIONS: This large single centre
      service evaluation confirms that unilateral injection of the greater occipital
      nerve is a safe, rapid-onset and effective treatment strategy in disabling
      headache disorders in children, with a range of diagnoses and severity of the
      condition, and with minimal side effects.

PMID- 29340792
TI  - Internal jugular vein variability predicts fluid responsiveness in cardiac
      surgical patients with mechanical ventilation.
AB  - BACKGROUND: To evaluate the efficacy of using internal jugular vein variability
      (IJVV) as an index of fluid responsiveness in mechanically ventilated patients
      after cardiac surgery. METHODS: Seventy patients were assessed after cardiac
      surgery. Hemodynamic data coupled with ultrasound evaluation of IJVV and inferior
      vena cava variability (IVCV) were collected and calculated at baseline, after a
      passive leg raising (PLR) test and after a 500-ml fluid challenge. Patients were
      divided into volume responders (increase in stroke volume >= 15%) and non
      responders (increase in stroke volume < 15%). We compared the differences in
      measured variables between responders and non-responders and tested the ability
      of the indices to predict fluid responsiveness. RESULTS: Thirty-five (50%)
      patients were fluid responders. Responders presented higher IJVV, IVCV and stroke
      volume variation (SVV) compared with non-responders at baseline (P < 0.05). The
      relationship between IJVV and SVV was moderately correlated (r = 0.51, P < 0.01).
      The areas under the receiver operating characteristic (ROC) curves for predicting
      fluid responsiveness were 0.88 (CI 0.78-0.94) for IJVV compared with 0.83 (CI
      0.72-0.91), 0.97 (CI 0.89-0.99), 0.91 (CI 0.82-0.97) for IVCV, SVV, and the
      increase in stroke volume in response to a PLR test, respectively. CONCLUSIONS:
      Ultrasound-derived IJVV is an accurate, easily acquired noninvasive parameter of
      fluid responsiveness in mechanically ventilated postoperative cardiac surgery
      patients, with a performance similar to that of IVCV.

PMID- 29340793
TI  - Neuroimaging Findings in Patients with Medication Overuse Headache.
AB  - Medication overuse headache (MOH) is a secondary headache syndrome defined as the
      deterioration of the headache associated with the overuse of analgesics. The
      prevalence of MOH is 1-2% in the general population and even up to 50% in special
      clinics. Overuse of abortive medications is highly associated with chronic daily
      headaches and also a known risk factor for headache evolution. Possible
      mechanisms include neural plasticity changes such as sensitization and defective
      endogenous pain inhibition. Psychological studies have suggested dependence, even
      addiction, in patients with MOH. Neuroimaging studies have provided valuable
      information concerning MOH pathophysiology. Magnetic resonance imaging analyzed
      by voxel-based morphometry showed gray matter volume changes in brain areas
      participating the pain modulations. Changes of brain function at similar areas
      have been revealed by positron emission tomography and functional magnetic
      resonance imaging studies. Many of these changes were correlated with either
      headache and/or analgesics parameters such as frequency and duration. These
      changes are typically reversible after successful treatment. Though the cause or
      consequence debate remains unsettled, we are more in favor of these findings as
      maladaptive changes to the frequent headaches or medication overuse. Of these
      brain areas involved in MOH, orbitofrontal cortex is of interest in several ways.
      In an early positron emission tomography study, the hypometabolism persists after
      successful treatment which implied a causal role. The following morphological
      studies showed the orbitofrontal cortex volume could predict treatment responses.
      Functional magnetic resonance imaging studies, task positive and also resting
      state ones, also reported changes within the mesocorticolimbic dopamine system,
      also known as reward system. Important brain areas of this system include ventral
      tegmental area, striatum, and orbitofrontal cortex. The system plays an important
      role in decision-making, dependence, and addiction, as implicated in
      psychological studies of MOH. Further studies on neuromodulation of this system
      may be considered in the treatment of MOH.

PMID- 29340794
TI  - A unified description of colloidal thermophoresis.
AB  - We use the dynamic length and time scale separation in suspensions to formulate a
      general description of colloidal thermophoresis. Our approach allows an
      unambiguous definition of separate contributions to the colloidal flux and
      clarifies the physical mechanisms behind non-equilibrium motion of colloids. In
      particular, we derive an expression for the interfacial force density that drives
      single-particle thermophoresis in non-ideal fluids. The issuing relations for the
      transport coefficients explicitly show that interfacial thermophoresis has a
      hydrodynamic character that cannot be explained by a purely thermodynamic
      consideration. Our treatment generalises the results from other existing
      approaches, giving them a clear interpretation within the framework of non
      equilibrium thermodynamics.

PMID- 29340795
TI  - The sesquiterpene botrydial from Botrytis cinerea induces phosphatidic acid
      production in tomato cell suspensions.
AB  - MAIN CONCLUSION: The phytotoxin botrydial triggers PA production in tomato cell
      suspensions via PLD and PLC/DGK activation. PLC/DGK-derived PA is partially
      required for botrydial-induced ROS generation. Phosphatidic acid (PA) is a
      phospholipid second messenger involved in the induction of plant defense
      responses. It is generated via two distinct enzymatic pathways, either via
      phospholipase D (PLD) or by the sequential action of phospholipase C and
      diacylglycerol kinase (PLC/DGK). Botrydial is a phytotoxic sesquiterpene
      generated by the necrotrophic fungus Botrytis cinerea that induces diverse plant
      defense responses, such as the production of reactive oxygen species (ROS). Here,
      we analyzed PA and ROS production and their interplay upon botrydial treatments,
      employing tomato (Solanum lycopersicum) cell suspensions as a model system.
      Botrydial induces PA production within minutes via PLD and PLC/DGK. Either
      inhibition of PLC or DGK diminishes ROS generation triggered by botrydial. This
      indicates that PLC/DGK is upstream of ROS production. In tomato, PLC is encoded
      by a multigene family constituted by SlPLC1-SlPLC6 and the pseudogene SlPLC7. We
      have shown that SlPLC2-silenced plants have reduced susceptibility to B. cinerea.
      In this work, we studied the role of SlPLC2 on botrydial-induced PA production by
      silencing the expression of SlPLC2 via a specific artificial microRNA. Upon
      botrydial treatments, SlPLC2-silenced-cell suspensions produce PA levels similar
      to wild-type cells. It can be concluded that PA is a novel component of the plant
      responses triggered by botrydial.

PMID- 29340797
TI  - Transcranial Doppler ultrasound in the ICU: it is not all sunshine and rainbows.

PMID- 29340796
TI  - The complete plastome of macaw palm [Acrocomia aculeata (Jacq.) Lodd. ex Mart.]
      and extensive molecular analyses of the evolution of plastid genes in Arecaceae.
AB  - MAIN CONCLUSION: The plastome of macaw palm was sequenced allowing analyses of
      evolution and molecular markers. Additionally, we demonstrated that more than
      half of plastid protein-coding genes in Arecaceae underwent positive selection.
      Macaw palm is a native species from tropical and subtropical Americas. It shows
      high production of oil per hectare reaching up to 70% of oil content in fruits
      and an interesting plasticity to grow in different ecosystems. Its domestication
      and breeding are still in the beginning, which makes the development of molecular
      markers essential to assess natural populations and germplasm collections.
      Therefore, we sequenced and characterized in detail the plastome of macaw palm. A
      total of 221 SSR loci were identified in the plastome of macaw palm.
      Additionally, eight polymorphism hotspots were characterized at level of
      subfamily and tribe. Moreover, several events of gain and loss of RNA editing
      sites were found within the subfamily Arecoideae. Aiming to uncover evolutionary
      events in Arecaceae, we also analyzed extensively the evolution of plastid genes.
      The analyses show that highly divergent genes seem to evolve in a species
      specific manner, suggesting that gene degeneration events may be occurring within
      Arecaceae at the level of genus or species. Unexpectedly, we found that more than
      half of plastid protein-coding genes are under positive selection, including
      genes for photosynthesis, gene expression machinery and other essential plastid
      functions. Furthermore, we performed a phylogenomic analysis using whole
      plastomes of 40 taxa, representing all subfamilies of Arecaceae, which placed the
      macaw palm within the tribe Cocoseae. Finally, the data showed here are important
      for genetic studies in macaw palm and provide new insights into the evolution of
      plastid genes and environmental adaptation in Arecaceae.

PMID- 29340798
TI  - Diagnostic implications of a small-voxel reconstruction for loco-regional lymph
      node characterization in breast cancer patients using FDG-PET/CT.
AB  - BACKGROUND: We evaluated the diagnostic implications of a small-voxel
      reconstruction for lymph node characterization in breast cancer patients, using
      state-of-the-art FDG-PET/CT. We included 69 FDG-PET/CT scans from breast cancer
      patients. PET data were reconstructed using standard 4 * 4 * 4 mm3 and small 2 *
      2 * 2 mm3 voxels. Two hundred thirty loco-regional lymph nodes were included, of
      which 209 nodes were visualised on PET/CT. All nodes were visually scored as
      benign or malignant, and SUVmax and TBratio(=SUVmax/SUVbackground) were measured.
      Final diagnosis was based on histological or imaging information. We determined
      the accuracy, sensitivity and specificity for both reconstruction methods and
      calculated optimal cut-off values to distinguish benign from malignant nodes.
      RESULTS: Sixty-one benign and 169 malignant lymph nodes were included. Visual
      evaluation accuracy was 73% (sensitivity 67%, specificity 89%) on standard-voxel
      images and 77% (sensitivity 78%, specificity 74%) on small-voxel images (p =
      0.13). Across malignant nodes visualised on PET/CT, the small-voxel score was
      more often correct compared with the standard-voxel score (89 vs. 76%, p < 
      0.001). In benign nodes, the standard-voxel score was more often correct (89 vs.
      74%, p = 0.04). Quantitative data were based on the 61 benign and 148 malignant
      lymph nodes visualised on PET/CT. SUVs and TBratio were on average 3.0 and 1.6
      times higher in malignant nodes compared to those in benign nodes (p <  0.001),
      on standard- and small-voxel PET images respectively. Small-voxel PET showed
      average increases in SUVmax and TBratio of typically 40% over standard-voxel PET.
      The optimal SUVmax cut-off using standard-voxels was 1.8 (sensitivity 81%,
      specificity 95%, accuracy 85%) while for small-voxels, the optimal SUVmax cut-off
      was 2.6 (sensitivity 78%, specificity 98%, accuracy 84%). Differences in accuracy
      were non-significant. CONCLUSIONS: Small-voxel PET/CT improves the sensitivity of
      visual lymph node characterization and provides a higher detection rate of
      malignant lymph nodes. However, small-voxel PET/CT also introduced more false
      positive results in benign nodes. Across all nodes, differences in accuracy were
      non-significant. Quantitatively, small-voxel images require higher cut-off
      values. Readers have to adapt their reference standards.

PMID- 29340799
TI  - Fully automated life support: an implementation and feasibility pilot study in
      healthy pigs.
AB  - BACKGROUND: Automated systems are available in various application areas all over
      the world for the purpose of reducing workload and increasing safety. However,
      such support systems that would aid caregivers are still lacking in the medical
      sector. With respect to workload and safety, especially, the intensive care unit
      appears to be an important and challenging application field. Whereas many closed
      loop subsystems for single applications already exist, no comprehensive system
      covering multiple therapeutic aspects and interactions is available yet. This
      paper describes a fully closed-loop intensive care therapy and presents a
      feasibility analysis performed in three healthy pigs over a period of 72 h each
      to demonstrate the technical and practical implementation of automated intensive
      care therapy. METHODS: The study was performed in three healthy, female German
      Landrace pigs under general anesthesia with endotracheal intubation. An arterial
      and a central venous line were implemented, and a suprapubic urinary catheter was
      inserted. Electrolytes, glucose levels, acid-base balance, and respiratory
      management were completely controlled by an automated fuzzy logic system based on
      individual targets. Fluid management by adaption of the respective infusion rates
      for the individual parameters was included. RESULTS: During the study, no manual
      modification of the device settings was allowed or required. Homoeostasis in all
      animals was kept stable during the entire observation period. All remote
      controlled parameters were maintained within physiological ranges for most of the
      time (free arterial calcium 73%, glucose 98%, arterial base excess 89%, and etCO2
      98%). Subsystem interaction was analyzed. CONCLUSIONS: In the presented study, we
      demonstrate the feasibility of a fully closed-loop system, for which we collected
      high-resolution data on the interaction and response of the different subsystems.
      Further studies should use big data approaches to analyze and investigate the
      interactions between the subsystems in more detail.

PMID- 29340800
TI  - Correction to: Psychiatric comorbidity and intimate partner violence among women
      who inject drugs in Europe: a cross-sectional study.
AB  - The original version of this article unfortunately missed the Acknowledgment.

PMID- 29340801
TI  - Maternal depression trajectories from pregnancy to 3 years postpartum are
      associated with children's behavior and executive functions at 3 and 6 years.
AB  - The objective of this study was to investigate how patterns of maternal
      depressive symptoms from mid-pregnancy to 3 years postpartum are associated with
      children's behavior at age 3 years and executive functions. Maternal depressive
      symptoms were measured from mid-pregnancy to 3 years postpartum. Growth mixture
      modeling was used on standardized maternal depression scores (n = 147) to
      identify trajectories. Children's behavioral problems and mental health
      symptomatology (internalizing, externalizing, and attention deficit hyperactivity
      disorder) were obtained at 3 and 6 years. EFs were assessed by a laboratory-based
      computerized task and maternal-report at 6 years. Multivariable linear
      regressions of children's outcomes against maternal depressive symptom
      trajectories were conducted (n = 103). Three distinct patterns of maternal
      depressive symptom trajectories were identified: low (n = 105), increasing (n =
      27), and decreasing (n = 15). Children of mothers whose depressive symptoms
      increased reported more problem behaviors at 3 years and poorer EFs at 6 years as
      assessed by both instruments, but no significant differences in mental health
      symptomatology at 6 years, relative to those whose mothers had consistently low
      depressive symptoms. Children whose mothers became less depressed over time had
      comparable levels of behavioral problems at age 3, executive functions, and
      internalizing and externalizing scores at age 6; and fewer reported ADHD
      behaviors at age 6, than those whose mothers remained less depressed over time.
      If mothers' depressive symptoms improve over the first 3 years postpartum, their
      children's outlook may be comparable to those whose mothers had consistently low
      depressive symptoms.

PMID- 29340802
TI  - Longitudinal trajectories of antidepressant use in pregnancy and the postnatal
      period.
AB  - Studies of antidepressant safety in pregnancy typically do not address complex
      patterns of use throughout pregnancy. We performed longitudinal trajectory
      modeling to describe patterns of antidepressant use in the first 32 weeks of
      pregnancy, and test whether these trajectories are associated with a reduction in
      birth weight or gestational age at delivery. Our study included 166 pregnant
      women with deliveries between 2011 and 2015 who were prescribed an antidepressant
      between 91 days prior to last menstrual period and 32 weeks of gestation. From
      electronic medical records, we estimated average daily dose and cumulative dose
      per week for the first 32 weeks of gestation and for the first 13 weeks
      postnatal. We clustered women with similar utilization patterns using k-means
      longitudinal modeling and assessed the associations between trajectory group and
      birth weight and gestational age at delivery. We identified four cumulative dose
      trajectory groups and three average daily dose trajectory groups in each period.
      Relative to the lowest trajectory group, the highest trajectory group during
      pregnancy was associated with reduced birth weight in multivariable analysis
      (average daily highest trajectory vs. lowest trajectory beta - 314.1 g, 95% CI -
      613.7, - 15.5) adjusted for depression severity score, maternal age, race, and
      pregnancy smoking. Trajectory groups were not associated with gestational age at
      delivery. The highest trajectory group of antidepressant use in pregnancy was
      associated with a modest reduction in birth weight but not with gestational age
      at delivery. Longitudinal trajectories allow for a dynamic visualization and
      quantification of medication use among pregnant women.

PMID- 29340803
TI  - Robust Exponential Memory in Hopfield Networks.
AB  - The Hopfield recurrent neural network is a classical auto-associative model of
      memory, in which collections of symmetrically coupled McCulloch-Pitts binary
      neurons interact to perform emergent computation. Although previous researchers
      have explored the potential of this network to solve combinatorial optimization
      problems or store reoccurring activity patterns as attractors of its
      deterministic dynamics, a basic open problem is to design a family of Hopfield
      networks with a number of noise-tolerant memories that grows exponentially with
      neural population size. Here, we discover such networks by minimizing probability
      flow, a recently proposed objective for estimating parameters in discrete maximum
      entropy models. By descending the gradient of the convex probability flow, our
      networks adapt synaptic weights to achieve robust exponential storage, even when
      presented with vanishingly small numbers of training patterns. In addition to
      providing a new set of low-density error-correcting codes that achieve Shannon's
      noisy channel bound, these networks also efficiently solve a variant of the
      hidden clique problem in computer science, opening new avenues for real-world
      applications of computational models originating from biology.

PMID- 29340804
TI  - Erratum to: Tc-99m methoxyisobutylisonitrile bone marrow imaging for predicting
      the levels of myeloma cells in bone marrow in multiple myeloma: correlation with
      CD38/CD138 expressing myeloma cells.

PMID- 29340805
TI  - Cardiorespiratory Fitness and Cardiovascular Disease Prevention: an Update.
AB  - PURPOSE OF REVIEW: Cardiovascular diseases account for nearly one third of all
      deaths globally. Improving exercise capacity and cardiorespiratory fitness (CRF)
      has been an important target to reduce cardiovascular events. In addition, the
      American Heart Association defined decreased physical activity as the fourth risk
      factor for coronary artery disease. Multiple large cohort studies have evaluated
      the impact of CRF on outcomes. In this review, we will discuss the role of CRF in
      reducing cardiovascular morbidity and mortality. RECENT FINDINGS: Recent data
      suggest that CRF has an important role in reducing not only cardiovascular and
      all-cause mortality, but also incident myocardial infarction, hypertension,
      diabetes, atrial fibrillation, heart failure, and stroke. Most recently, its role
      in cancer prevention started to emerge. CRF protective effects have also been
      seen in patients with prior comorbidities like prior coronary artery disease,
      heart failure, depression, end-stage renal disease, and stroke. The prognostic
      value of CRF has been demonstrated in various patient populations and
      cardiovascular conditions. Higher CRF is associated with improved survival and
      decreased incidence of cardiovascular diseases (CVD) and other comorbidities
      including hypertension, diabetes, heart failure, and atrial fibrillation.

PMID- 29340806
TI  - Distribution of IL28B and IL10 polymorphisms as genetic predictors of treatment
      response in Pakistani HCV genotype 3 patients.
AB  - There are over 10 million hepatitis C virus (HCV)-infected patients in Pakistan.
      For these patients, a combination of interferon with ribavirin is the most
      economical and easily available treatment. Single-nucleotide polymorphisms in
      interleukin genes have been reported to be associated with the pathogenesis and
      clearance of HCV, and sustained virologic response (SVR). An interleukin 28B
      (IL28B) gene polymorphism has been shown to modify treatment outcomes, but the
      effects of interleukin 10 (IL10) polymorphisms have not been previously assessed
      in the Pakistani population. The present study was conducted with 302 subjects
      categorized into two groups: 100 healthy volunteers (Group I) and 202 patients
      with chronic HCV (Group II). Patients within Group II were further divided into
      two subgroups according to therapeutic response: SVR (responders = 132) and NR
      (non-responders/relapsers = 70). IL28B (rs8099917, rs12979860) and IL10
      (rs1800872, rs1800871, rs1800896) gene polymorphisms were studied in all
      subjects. A significant difference in the distribution of IL28B rs12979860C/T
      genotypes between the two groups (p<0.05) was observed, while of the three IL10
      polymorphisms, a significant difference was only shown for rs1800896 A/G.
      Haplotype analysis (IL28B and IL10) showed a significant association of TTGTC and
      TTGTA when comparing the groups. There was a strong association of the favorable
      alleles rs8099917T and rs12979860C in the SVR group as compared with the NR group
      (p<0.05), and rs1800896 also showed an association with the SVR group as compared
      to the NR group (p<0.004). Haplotype analysis showed significant associations
      when comparing the SVR and NR subgroups, i.e. TCATC (p=0.009), TTGTA (p=0.005),
      TCATA (p<0.0005), TCACA (p=0.002), GTGCC (p=0.002) and TCGTC (p=0.005). IL28B
      (rs8099917 and rs12979860) and IL10 (rs1800896) polymorphisms alone, or in
      combination, are good predictors of therapeutic response in HCV-3a patients.

PMID- 29340807
TI  - Long-Term Outcome of Infliximab Optimization for Overcoming Immunogenicity in
      Patients with Inflammatory Bowel Disease.
AB  - BACKGROUND: Preliminary data suggest that treatment optimization can reverse
      immunogenicity and regain response in patients with IBD and secondary loss of
      response (SLR) to anti-TNF therapy due to antidrug antibodies. However, data
      regarding the long-term outcome of these patients are scarce. AIMS: We aimed to
      investigate drug retention in IBD patients of whom infliximab was optimized to
      overcome immunogenicity and variables associated with drug retention. METHODS:
      This was a retrospective, multicenter study of consecutive IBD patients with
      antibodies to infliximab (ATI), based on either proactive or reactive therapeutic
      drug monitoring, who underwent infliximab optimization (increasing dose,
      shortening interval, adding an immunomodulator, or combination) to overcome
      immunogenicity from September 2012 to July 2015; they were followed through
      December 2015. ATI were analyzed using the drug-tolerant Prometheus homogeneous
      mobility shift assay. Drug retention was defined as no need for drug
      discontinuation due to SLR or serious adverse event. RESULTS: Our cohort
      consisted of 22 patients (Crohn's disease, n = 15). At the end of follow-up
      [median, (IQR): 17.3 (10.5-32.8) months] 77% (15/22) of patients were still on
      drug. Univariable Cox proportional hazards regression analysis identified first
      detectable ATI titer as the only variable associated with drug retention (HR:
      0.89; 95% CI: 0.82-0.98, p = 0.016). Receiver-operating characteristic analysis
      identified an ATI titer < 8.8 U/mL associated with drug retention. CONCLUSIONS:
      In real-life clinical practice, optimization of infliximab therapy can prevent
      drug discontinuation in approximately 3/4 of patients with ATI, especially in
      those with low titers. Large prospective studies are needed to confirm these
      data.

PMID- 29340808
TI  - Does advancement in stapling technology with triple-row and enhanced staple
      configurations confer additional safety? A matched comparison of 340 stapled
      ileocolic anastomoses.
AB  - BACKGROUND: Over the past few decades, studies have focused on the safety of
      stapled anastomosis, especially when compared to that of the handsewn technique.
      However, studies on the improvement of stapling technology are limited. This
      study aimed to investigate whether linear triple-row staples (tri-staples) had
      any advantage over double-row staples. METHODS: This is a retrospective review of
      all cases of functional end-to-end anastomoses with linear staplers performed at
      two centers between 2005 and 2015. Data were retrieved from a prospectively
      maintained database. Cases of anastomoses performed with double-row (DS) and
      triple-row (TS) staples were matched according to propensity scores. The rates of
      anastomotic leakage, bleeding, reoperation, and 30-day mortality were compared.
      RESULTS: Functional end-to-end ileocolic anastomoses were performed in 563
      consecutive patients during the study period. Double- and triple-row stapling
      devices were used in 389 and 174 anastomoses, respectively. With propensity score
      matching, 170 cases were chosen from each group. Both groups showed comparable
      baseline characteristics. The anastomotic leakage, anastomotic bleeding, and
      intra-abdominal collection rates were 2.4 and 0% (p = 0.123), 1.2 and 0% (p =
      0.499), and 3.5 and 1.2% (p = 0.283) for DS and TS, respectively. The reoperation
      and 30-day mortality rates were 5.9 and 1.8% (p = 0.048) and 0.6 and 1.2% (p =
      1.000) for DS and TS, respectively. The median lengths of stay were 5 and 6 days
      (p = 0.072) for DS and TS, respectively. CONCLUSION: Anastomoses with triple-row
      staples tended to have a lower morbidity rate, but a significant advantage over
      double-row staples was not demonstrated in this study.

PMID- 29340809
TI  - Randomized controlled study of intraincisional infiltration versus
      intraperitoneal instillation of standardized dose of ropivacaine 0.2% in post
      laparoscopic cholecystectomy pain: Do we really need high doses of local
      anesthetics-time to rethink!
AB  - BACKGROUND: Earlier studies done to compare the efficacy of use of local
      anesthetics at intraperitoneal location versus intraincisional use had utilized
      equal amount of drugs at the two locations, usually 10-20 ml. Using this large
      amount of drug in the small space of intraincisional location as compared to
      similar amount of drug in large intraperitoneal space created an inadvertent bias
      in favor of patients receiving the drug intraincisionally so these patients
      naturally experienced less pain. AIMS AND OBJECTIVES: To conduct a randomized,
      triple-blind, placebo-controlled study by standardizing dose of local anesthetic,
      to compare the effectiveness of intraperitoneal against intraincisional use of
      ropivacaine 0.2% for post-laparoscopic cholecystectomy pain relief. MATERIALS AND
      METHODS: 294 patients underwent elective 4-port laparoscopic cholecystectomy.
      Patients were triple blindly randomized. All patients received ~ 23 ml of
      solution, of which 20 ml was given intraperitoneally (1 ml/cm; 16 ml along right
      hemi-dome and 4 ml in gall bladder fossa) and ~ 3 ml intraincisionally (1 ml/cm
      of length of incision). Solution was either normal saline or drug (0.2%
      ropivacaine) depending on the group [controls (n = 86), intraperitoneal group (n
      = 100), and intraincisional group (n = 108)]. 5 different pain scales were used
      for assessment of overall pain. Pain scores were assessed at 5 points of time.
      RESULTS: Patients in intraincisional group showed significantly less overall pain
      and rescue analgesia requirement (p < 0.05). Intraincisional group showed
      significantly less overall pain (p < 0.05) as compared to intraperitoneal group;
      however, use of rescue analgesia was comparable in the two groups (p > 0.05); and
      shoulder pain was significantly less in intraperitoneal group (p < 0.05).
      CONCLUSION: The intraincisional use of injection ropivacaine at its minimum
      concentration of 0.2% in minimal doses of 1 ml/cm at the end of procedure
      provides significantly more post-operative analgesia as compared to
      intraperitoneal group and controls. However, for controlling shoulder pain, the
      use of intraperitoneal ropivacaine is desirable.

PMID- 29340810
TI  - Ureteral stents increase risk of postoperative acute kidney injury following
      colorectal surgery.
AB  - BACKGROUND: Ureteral stents are commonly placed before colorectal resection to
      assist in identification of ureters and prevent injury. Acute kidney injury (AKI)
      is a common cause of morbidity and increased cost following colorectal surgery.
      Although previously associated with reflex anuria, prophylactic stents have not
      been found to increase AKI. We sought to determine the impact of ureteral stents
      on the incidence of AKI following colorectal surgery. METHODS: All patients
      undergoing colon or rectal resection at a single institution between 2005 and
      2015 were reviewed using American College of Surgeons National Surgical Quality
      Improvement Program dataset. AKI was defined as a rise in serum creatinine to >=
      1.5 times the preoperative value. Univariate and multivariate regression analyses
      were performed to identify independent predictors of AKI. RESULTS: 2910 patients
      underwent colorectal resection. Prophylactic ureteral stents were placed in 129
      patients (4.6%). Postoperative AKI occurred in 335 (11.5%) patients during their
      hospitalization. The stent group demonstrated increased AKI incidence (32.6% vs.
      10.5%; p < 0.0001) with bilateral having a higher rate than unilateral stents.
      Hospital costs were higher in the stent group ($23,629 vs. $16,091; p < 0.0001),
      and patients with bilateral stents had the highest costs. Multivariable logistic
      regression identified predictors of AKI after colorectal surgery including age,
      procedure duration, and ureteral stent placement. CONCLUSIONS: Prophylactic
      ureteral stents independently increased AKI risk when placed prior to colorectal
      surgery. These data demonstrate increased morbidity and hospital costs related to
      usage of stents in colorectal surgery, indicating that placement should be
      limited to patients with highest potential benefit.

PMID- 29340811
TI  - A word of caution: never use tacks for mesh fixation to the diaphragm!
AB  - BACKGROUND: The mesh fixation technique used in repair of hiatal hernias and
      subxiphoid ventral and incisional hernias must meet strenuous requirements. In
      the literature, there are reports of life-threatening complications with cardiac
      tamponade and a high mortality rate on using tacks. The continuing practice of
      tack deployment for mesh fixation to the diaphragm and esophageal hiatus should
      be critically reviewed. METHODS: In a systematic search of the available
      literature in May 2017, 23 cases of severe penetrating cardiac complications were
      identified. The authors became aware of two other cases in which they acted as
      medical experts. Furthermore, the instructions for use issued by the
      manufacturers of the tacks were reviewed with regard to their deployment in the
      diaphragm. RESULTS: Twenty-three of 25 cases (92%) with severe cardiac injuries
      and subsequent cardiac tamponade were triggered by the use of tacks in the
      diaphragm. In six cases (24%), these related to ventral and incisional hernias
      with extension to the subxiphoid area, and in 19 cases (76%) to mesh-augmented
      hiatoplasty. Twelve of 25 (48%) patients died as a result of pericardial and/or
      heart muscle injury with cardiac tamponade despite heart surgery intervention. In
      the tack manufacturers' instructions for use, their deployment in the diaphragm,
      in particular in the vicinity of the heart, is contraindicated. Likewise, the
      existing guidelines urgently advise against the use of tacks in the diaphragm,
      recommending instead alternative fixation techniques. CONCLUSIONS: Tacks should
      not be used for mesh fixation in the diaphragm above the costal arch.

PMID- 29340812
TI  - Partial amniotic carbon dioxide insufflation (PACI) during minimally invasive
      fetoscopic interventions on fetuses with spina bifida aperta.
AB  - BACKGROUND: Percutaneous partial amniotic carbon dioxide insufflation (PACI) is
      one of the most important means for improving visualization during minimally
      invasive fetoscopic surgery of fetal spina bifida. The purpose of the present
      study was to analyze maternal and fetal safety aspects of PACI in a recent
      patient cohort and to present management improvements. METHODS: PACI under
      general materno-fetal anesthesia was performed during 65 interventions for
      fetoscopic patch coverage of fetal spina bifida aperta between 21 + 0 and 29 + 1
      weeks of gestation. Filtered carbon dioxide was insufflated into the amniotic
      cavity via three percutaneously introduced trocars. Maternal ventilatory and
      hemodynamic parameters during PACI as well as insufflation pressures, BMI,
      parity, and placental position were recorded and statistically analyzed in order
      to detect potential risk groups. RESULTS: Maternal respiration parameters during
      PACI showed a typical variation over time, which was similar in patients with BMI
      <= 25 or BMI > 25. The necessary insufflation pressures were significantly higher
      in nulliparae than multiparae. There was no statistically significant
      relationship between insufflation pressure and maternal BMI, or between the
      expired maternal carbon dioxide concentration (etCO2) and the placental position.
      PACI was safe for all mothers and fetuses. Postnatal demise in one neonate, one
      fetus, and two infants occurred unrelated to PACI and resulted from trisomy 13,
      infection, and severe Chiari II malformations, respectively. CONCLUSION: PACI
      seems safe in order to improve visualization of intraamniotic contents during
      minimally invasive fetoscopic surgery. Nevertheless, continued assessments of its
      benefits and risks are important.

PMID- 29340813
TI  - Impact of laparoscopy in patients aged over 70 years requiring distal
      pancreatectomy: a French multicentric comparative study.
AB  - BACKGROUND: Few data are available concerning short-term results of minimally
      invasive surgery in patients > 70 years old requiring distal pancreatectomy. The
      aim of this study was to compare short-term results after laparoscopic (LDP)
      versus open distal pancreatectomy (ODP) in this subgroup of patients. METHODS:
      All patients > 70 years who underwent distal pancreatectomy in 3 expert centers
      between 1995 and 2017 were included and data were retrospectively analyzed.
      Demographic, intraoperative data and postoperative outcomes in LDP and ODP groups
      were compared. RESULTS: A distal pancreatectomy was performed in 109 elderly
      patients; LDP group included 53 patients while ODP group included 56. There were
      55 (50.5%) males and 54 (49.5%) women with a median age of 75 years (range 70
      87). Fifty (45.9%) patients were 70-74, 40 (36.7%) patients were 75-79, and 19
      (17.4%) patients were over 80 years. Nine (8.2%) patients required conversion to
      open surgery. The median operative time was not different between LDP and ODP
      (204 vs. 220 min, p = 0.62). The intraoperative blood loss was significantly
      lower in the LDP group (238 +/- 312 vs. 425 +/- 582 ml, p = 0.009) with no
      difference regarding the intraoperative transfusion rate. 90-day mortality (0 vs.
      5%, p = 0.42), overall complication (45.4 vs. 51.8%, p = 0.53), major
      complication (18.2 vs. 12.5%, p = 0.43), grade B/C pancreatic fistula (6.8 vs.
      7.1%, p = 0.71), were comparable in the 2 groups. Only postoperative confusion
      rate was significantly lower in the LDP group (4.5 vs. 25%, p = 0.01). Median
      length of stay was significantly lower in the LDP group (14 +/- 10 vs. 16 +/- 11
      days, p = 0.04). R0 resection was performed in 94% of LDP patients and 89% in ODP
      patients without significant difference (p = 0.73). CONCLUSIONS: The laparoscopic
      approach seems to reduce blood loss, postoperative confusion, and length of stay
      in elderly patients requiring distal pancreatectomy.

PMID- 29340814
TI  - Comparison of mesh fixation devices for laparoscopic ventral hernia repair: an
      experimental study on human anatomic specimens.
AB  - BACKGROUND: As there is a lack of clarity in terms of the tensile strength of
      mesh fixation for laparoscopic ventral hernia repair (LVHR), our aim was to
      investigate the immediate tensile strength of currently available mesh fixation
      devices on human anatomic specimens. METHODS: Sixteen recently deceased body
      donators (mean body mass index of 24.4 kg/m2) were used to test the immediate
      tensile strength (Newton) of 11 different LVHR mesh fixation devices. RESULTS:
      Each of the 11 different laparoscopic fixation devices was tested 44 times. Non
      articulating tackers provided higher fixation resistance to tensile stress in
      comparison to articulating tackers (5.1-mm ReliaTackTM: 16.9 +/- 8.7 N vs. 12.2
      +/- 5.6 N, p = 0.013; 7-mm ReliaTackTM: 19.8 +/- 9.4 N vs. 15.0 +/- 7.0 N, p =
      0.007). Absorbable tacks with a greater length, i.e. >=6 mm (7-mm ReliaTackTM, 6
      mm SorbaFixTM and 7.2-mm SecureStrapTM) had significantly higher fixation tensile
      strength than tacks with a shorter length, i.e. < 6 mm (5.1-mm ReliaTackTM and
      5.1-mm AbsorbaTackTM) (p < 0.001). Furthermore, transfascial sutures (PDS 2-0
      sutures 26.3 +/- 5.6 N) provided superior fixation tensile strength than 5.1-mm
      AbsorbaTackTM (13.6 +/- 7.3 N) and cyanoacrylate glues such as LiquiBand FIX8TM
      (3.5 +/- 2.4 N) (p < 0.001, respectively). There was a significant deterioration
      in fixation capacity in obese body donators with a body mass index > 30 kg/m2
      (13.8 +/- 8.0 vs. 17.9 +/- 9.7 N, p = 0.044). CONCLUSIONS: Although articulating
      laparoscopic tackers improve accessibility and facilitate the utilization of
      tacks within the fixation weak spot adjacent to the trocar placement, an
      articulating shaft that is not ergonomic to use may limit mechanisms of force
      transmission. For mesh fixation in LVHR, transfascial sutures and tacks with a
      longer length provide better immediate fixation tensile strength results.

PMID- 29340815
TI  - 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  - BACKGROUND AND AIMS: Surgical resection is considered the first treatment option
      for submucosal tumors (SMTs) originating from the muscularis propria layer while
      submucosal tunneling endoscopic resection (STER) is proved to be a safe and
      effective method for treating SMTs. This study aimed to compare video-assisted
      thoracoscopic enucleation (VATE) with STER for treating esophageal SMTs. METHODS:
      Sixty-six patients with small esophageal SMTs were prospectively randomized from
      July 2014 to December 2015. After exclusion of 8 patients, 58 subjects scheduled
      for STER or VATE were enrolled. Clinicopathological, endoscopic, and adverse
      events (AEs) data were collected and analyzed between STER and VATE. RESULTS:
      Forty-six males and 12 females with a mean age of 46.1 +/- 9.4 years were
      randomized to the STER (n = 30) and VATE (n = 28) groups, respectively.
      Demographics and lesion features were similar between the two groups. Median
      procedure time was shorter in the STER group than the VATE group (44.5 vs. 106.5
      min, P < 0.001); cost was lower in the STER group (4499.46 vs. 6137.32 USD, P =
      0.010). Median decrease in hemoglobin levels post-procedure was - 1.6 g/L in the
      STER group and 14.7 g/L after VATE (P = 0.001). Lower postoperative pain scores
      were found in the STER group compared with the VATE group (2 vs. 4, P < 0.001).
      No recurrent or residual tumors were found in either group. En bloc resection
      rates, complete resection rates, hospital times, and post-procedure AEs were
      similar between two groups. The en bloc resection rates for SMTs < 20.0 mm were
      100% in both groups while STER achieved only 71.4% en bloc resection rate for
      SMTs >= 20.0 mm. CONCLUSION: STER and VATE are comparably effective for
      esophageal SMTs; however, STER is superior to VATE with shorter operation time
      and decreased cost, and seems safer than VATE. STER is recommended for SMTs <
      20.0 mm while VATE is recommended for SMTs with a transverse diameter > 35.0 mm.
      Clinical trail registration statement: This study is registered at
      http://www.chictr.org.cn/showproj.aspx?proj=4814 . The registration
      identification number is ChiCTR-TRC-14004759. The registration date is April 30,
      2014.

PMID- 29340816
TI  - Expanding indications of robotic thyroidectomy.
AB  - BACKGROUND: Robotic thyroidectomy has many advantages with comparable oncologic
      safety over conventional open surgery in low-risk differentiated thyroid cancer
      cases. However, there have been few reports on the outcomes of patients who have
      been treated with robotic thyroidectomy for more advanced thyroid cancer. The aim
      of this study was to investigate the validity of expanding indications of robotic
      thyroidectomy for more advanced thyroid cancer. METHODS: The data of 80 patients
      with thyroid cancer who underwent robotic total thyroidectomy between January
      2013 and December 2014 performed by a single surgeon at Chung-Ang University
      Hospital were retrospectively reviewed. Among them, 40 patients who had cancer
      larger than 2 cm or suspicious capsular invasion, or central lymph node (LN)
      metastasis in preoperative pathologic and radiologic examinations were
      categorized into the more advanced thyroid cancer group and the remaining
      patients into the early thyroid cancer group. We compared surgical safety and
      surgical completeness parameters between the two groups. RESULTS: The patients in
      more advanced thyroid cancer group had larger tumors, more extrathyroidal
      extension, and higher T stages. Surgical safety parameters, such as
      hypoparathyroidism, vocal cord palsy, and other complications did not differ
      significantly between the two groups. Surgical completeness parameters, such as
      the mean number of retrieved LNs, median values of the stimulated thyroglobulin
      levels, and the proportion of patients with stimulated thyroglobulin levels less
      than 1 ng/mL, also did not differ significantly. CONCLUSIONS: The outcomes of the
      patients with more advanced thyroid cancer who were treated with robotic
      thyroidectomy were comparable to those of the early cancer group patients. Well
      designed investigations that are conducted at multiple centers are needed to
      affirm the validity of expanding indications of robotic thyroidectomy.

PMID- 29340817
TI  - Adenoma detection rate metrics in colorectal cancer surveillance colonoscopy.
AB  - BACKGROUND: A target goal for screening adenoma detection rate (S-ADR) of >= 25%
      has been set to define high-quality colonoscopy performance. However, there is no
      current accepted target goal for ADR in colorectal cancer (CRC) surveillance.
      This makes quality assessment challenging when physicians perform cancer
      surveillance colonoscopy but minimal screening procedures. METHODS: In this
      cohort study, consecutive colonoscopies performed at either Rush University
      Medical Center or Rush Oak Park Hospital by a gastroenterologist or colorectal
      surgeon in average risk screening population and CRC surveillance population were
      reviewed retrospectively from 2006 to 2012 and prospectively from 2013 to 2016.
      ADR in first surveillance colonoscopy following surgical resection of CRC (CRC
      ADR) was reported in high-quality detectors (HQD) or low-quality detectors (LQD)
      based on achievement of 25% ADR in consecutive screening colonoscopy in average
      risk patients. Pearson's correlation was used to describe the association between
      individual S-ADR and CRC-ADR for colonoscopists. RESULTS: There was a very strong
      positive correlation (r = 0.88, p = 0.002) between ADR in average risk screening
      and first time CRC surveillance. For HQD as defined by S-ADR >= 25% (n = 10
      colonoscopists), the CRC-ADR was 37.7% (78/207, SD 8%) which was very similar to
      their respective S-ADR of 33.4% (816/2440, p = 0.22). For LQD (n = 5
      colonoscopists), the CRC-ADR was 20.2% (40/198) which was similar to their
      respective S-ADR of 20.1% (119/591, p = 0.99). The CRC-ADR was significantly
      higher for HQD than for LQD (37.7 vs. 20.2%, p < 0.0001). CONCLUSIONS: The major
      finding of this study is a defined CRC-ADR for HQD based on the ability to
      achieve S-ADR >= 25%. S-ADR strongly correlates with CRC-ADR. CRC-ADR is quite
      similar to the colonoscopists' respective S-ADR for both HQD and LQD. For
      colonoscopists who perform limited screening colonoscopies but do perform CRC
      surveillance colonoscopies, ADR metrics similar to S-ADR to assess quality in
      colonoscopy could be considered.

PMID- 29340818
TI  - Changes in plasma albumin levels in early detection of infectious complications
      after laparoscopic colorectal cancer surgery with ERAS protocol.
AB  - BACKGROUND: Combination of laparoscopic approach with ERAS protocol in colorectal
      surgery allows for an early discharge. However there is a risk that some of the
      discharged patients are developing, asymptomatic at the time, infectious
      complications. This may lead to a delay in diagnostics and proper treatment
      introduction. We aimed to assess the usefulness of preoperative plasma albumin
      concentration and their changes as indicators of infectious complications in
      patients undergoing colorectal cancer surgery. METHODS: Prospective analysis
      included 105 consecutive patients who underwent laparoscopic colorectal cancer
      resection between August 2014 and September 2016. In all cases standardised 16
      item perioperative care ERAS protocol was used (mean compliance > 85%). Patients
      with IBD, distant metastases, undergoing emergency or multivisceral resection
      were excluded. Blood samples were collected preoperatively and on POD 1, 2, 3.
      Plasma albumin concentration was measured. Patients were divided into two groups
      depending on the presence of infectious complications. We analysed the
      differences in the levels of albumin and the dynamics of changes. RESULTS: Group
      1-82 not complicated patients, Group 2-23 patients with at least one infectious
      complication. Preoperatively, there were no significant differences in the levels
      of serum albumin between those groups (Group 1-38.7 +/- 4.9 g/l; Group 2-37.7 +/-
      5.0 g/l). In postoperative period, decrease was observed in both (POD 1: Group 1
      36.5 +/- 4.2 g/l, Group 2-34.7 +/- 4.2 g/l, p = 0.07; POD 2: Group 1-36.2 +/- 4.1
      g/l, Group 2-32.6 +/- 5.6 g/l, p = 0.01; POD 3: Group 1-36.0 +/- 4.4 g/l, Group 2
      30.9 +/- 3.5 g/l, p = 0.01). The decrease was significantly greater in Group 2 on
      POD 2 and 3. CONCLUSIONS: We showed that a regular measurement of albumin in the
      early postoperative days may be beneficial in the detection of postoperative
      infectious complications. Although changes in albumins are observed early after
      surgery, this parameter is relatively unspecific.

PMID- 29340819
TI  - Laparoscopic liver resection for colorectal liver metastasis patients allows
      patients to start adjuvant chemotherapy without delay: a propensity score
      analysis.
AB  - BACKGROUND: Although adjuvant chemotherapy (AC) is widely used after liver
      resection (LR) for colorectal liver metastasis (CRLM), surgical invasiveness may
      lead to delay in starting AC, which is preferably started within 8 weeks
      postoperative. We investigated whether laparoscopic liver resection (LLR) for
      CRLM facilitates AC start without delay. METHODS: Between November 2014 and
      December 2016, 117 consecutive CRLM patients underwent LR followed by AC. LLR and
      OLR were performed in 30 and 87 patients, respectively. After propensity score
      matching on clinical characteristics, oncologic features, and type of resection,
      the time interval between liver resection and AC start was compared between LLR
      (n = 22) and OLR (n = 44) groups. RESULTS: After propensity score matching, major
      LR was performed in 8/22 (36%) and 15/44 (34%) cases of LLR and OLR groups,
      respectively (P = 1.0). Clinical-pathological characteristic and intraoperative
      findings were comparable between two groups. There was no significant difference
      in postoperative complications between the two groups. The time interval between
      liver resection and AC start was significantly shorter in LLR than in OLR group
      (43 +/- 10 versus 55 +/- 18 days, P = 0.012). While 15/44 (34%) patients started
      AC after 8 weeks postoperative in OLR group, all patients in LLR group started AC
      within 8 weeks. CONCLUSIONS: LLR for CRLM is associated with quicker return to AC
      when compared to OLR. The delivery of AC without delay allows CRLM patients to
      optimize the oncologic treatment sequence.

PMID- 29340822
TI  - A preclinical animal study of a novel, simple, and secure duct and vessel
      occluder for laparoscopic surgery.
AB  - BACKGROUND: Secure occlusion of large blood vessels and ductal structures is
      critical to all surgeries and remains a challenge in many minimally invasive
      procedures. This study compares in vivo use of the Amsel Occluder (AO) for secure
      laparoscopic blood vessel and duct closure, with one of the many commercially
      available hemoclips (Ligaclip(r)), in the porcine model. METHODS: Laparoscopic
      closure of vessels and ducts was performed on 12 swine to compare the ease of
      use, safety and efficacy of the AO with a hemoclip, as well as the tissue
      response at > 30 days (10 swine). All vessels and ducts were occluded and then
      transected between the occluding clips. Any bleeding or leakage was noted. In the
      chronic study, confirmation of satisfactory vessel occlusion post nephrectomy was
      determined by laparotomy as well as by contrast angiography and venography. The
      tissue response and healing was evaluated by a histopathological study for the
      effects of any biological incompatibilities. RESULTS: In the acute laparoscopic
      study, a total of 24 occlusions between 2 and 10 mm were performed with the AO (n
      = 19) and hemoclip (n = 5). In the chronic study, 5 nephrectomies (AO n = 3,
      hemoclip N = 2) and 5 cholecystectomies (AO n = 3, hemoclip n = 2) were performed
      with survival ranging from 42 to 72 days. One pig who sustained a splenic injury
      at trocar insertion and suffered a delayed ruptured spleen with massive
      hemorrhage on postoperative day 22. Unlike occlusion with the AO, multiple
      hemoclips were used for each vessel occlusion. Histopathological examination
      showed no difference in the tissue response and healing of the AO and hemoclip.
      CONCLUSIONS: The Amsel Vessel occluder delivered laparoscopically provides an
      occlusion similar to a hand-sewn transfixion suture, is simple to use, and
      creates an occlusion which is not only more secure, but also as safe with respect
      to the health of the surrounding tissues, as that of the widely used hemoclip
      (Ligaclip(r)).

PMID- 29340821
TI  - A novel and safe approach: middle cranial approach for laparoscopic right
      hemicolon cancer surgery with complete mesocolic excision.
AB  - BACKGROUND: Mastering right hemicolectomy techniques using laparoscopy in
      colorectal cancer surgery is very difficult. Although the long-term prognosis of
      laparoscopic right hemicolectomy (LRH) and complete mesocolic excision is
      unquestionable, different surgeons have their own opinions on routes of
      conducting LRH. OBJECTIVES: LRH surgery is very complex due to the upper
      abdominal anatomical structure and vascular variation. Therefore, it has been
      considered the most difficult of all colorectal cancer surgeries. Our innovative
      middle cranial approach (MCA) was developed to avoid unnecessary injuries and
      minimize the operative time, thereby reducing the patient's hospital stay and
      improving their short-term prognosis. METHODS: We compared 90 colon cancer
      patients who underwent the MCA between January 2016 and January 2017 with 82
      patients who underwent the conventional central approach conducted by the same
      group of physicians (with Dr Cui as the surgeon) from 2011 to 2015. A short-term
      statistical analysis was performed. RESULTS: A total of 90 patients were
      included: 43 men and 47 women. Twenty-three patients underwent abdominal surgery
      (including stomach, rectum, and sigmoid colon surgery; appendectomy; and uterine
      attachment surgery). The median age of these patients was 62.6 (28-85) years; the
      median BMI was 22.9 (14.7-33.3) kg/m2; the mean bleeding volume was 53.9 (10-100)
      ml; the mean tumour diameter was 5.7 (0.8-9) cm, and the average number of lymph
      nodes detected was 19.2 (7-49). CONCLUSIONS: Our study showed that radical
      resection of right-sided colon cancer using the MCA was safe and feasible for the
      treatment of colorectal cancer patients.

PMID- 29340823
TI  - Endoscopic perforations: what are the indications for surgery?
AB  - BACKGROUND: Despite their low occurrence, endoscopic perforations (EPs) are
      concerning. Some predictive factors have been identified, and EP management is
      debated, whether non-surgical (medical and/or endoscopic) or surgical. The
      objective was to elaborate a predictive score for surgical management of EP.
      METHODS: All the patients addressed for upper and lower EP, except oesophageal
      EP, were retrospectively included (2004-2015). Demographic data, endoscopic
      features (indication, location, type), clinical, biological and radiological
      presentations of EP were reviewed. Management of EP and outcomes were recorded. A
      predictive score was constructed by multiple linear regression and a cut-off
      value for surgical management was identified. Additional subgroup analysis was
      performed according to the location of EP (upper and lower). RESULTS: Among 41150
      endoscopic procedures, 44 patients (22 males, median age = 65 years [22-87])
      presenting with EP were included (0.09%). Lower gastrointestinal (GI) endoscopy
      was mostly performed (66%). EP diagnosis was immediate in 73% of the cases (n =
      32). Non-surgical management was efficient in 2/3 cases treated medically alone,
      and 18/20 cases treated by endoscopy. Surgical management was always successful
      (n = 24/24). In case of peritonitis, surgery was systematically required, whereas
      easily required in case of delayed diagnostic of EP. The EP score was based on
      the presence of previous abdominal surgery, lower GI endoscopy and diagnostic
      endoscopy. A cut-off EP score of 22.8% for surgery was chosen; it was associated
      with a specificity and sensitivity of 40 and 100%, respectively. When subgroups
      were analysed according to EP location, the EP score was still based on the
      presence of previous abdominal surgery and diagnostic endoscopy. The cut-off was
      6.3 and 73.3% for upper (specificity: 73%, sensitivity: 100%) and lower (89 and
      45%) locations, respectively. CONCLUSION: The predictive EP score may avoid
      inappropriate surgical management, as well as delayed surgery after non-surgical
      management failure. Forthcoming study should prospectively validate this score.

PMID- 29340824
TI  - A software-based tool for video motion tracking in the surgical skills assessment
      landscape.
AB  - BACKGROUND: The use of motion tracking has been proved to provide an objective
      assessment in surgical skills training. Current systems, however, require the use
      of additional equipment or specialised laparoscopic instruments and cameras to
      extract the data. The aim of this study was to determine the possibility of using
      a software-based solution to extract the data. METHODS: 6 expert and 23 novice
      participants performed a basic laparoscopic cholecystectomy procedure in the
      operating room. The recorded videos were analysed using Kinovea 0.8.15 and the
      following parameters calculated the path length, average instrument movement and
      number of sudden or extreme movements. RESULTS: The analysed data showed that
      experts had significantly shorter path length (median 127 cm vs. 187 cm, p =
      0.01), smaller average movements (median 0.40 cm vs. 0.32 cm, p = 0.002) and
      fewer sudden movements (median 14.00 vs. 21.61, p = 0.001) than their novice
      counterparts. CONCLUSION: The use of software-based video motion tracking of
      laparoscopic cholecystectomy is a simple and viable method enabling objective
      assessment of surgical performance. It provides clear discrimination between
      expert and novice performance.

PMID- 29340825
TI  - Laparoscopic surgery in colon cancer patients treated with chronic anti
      thrombotic therapy.
AB  - BACKGROUND: Anti-thrombotic medications are commonly used for the treatment and
      prevention of cardiovascular diseases. Laparoscopic resection of colon cancer has
      generally been accepted with favorable outcomes being reported in randomized
      control trials. However, the safety and efficacy of laparoscopic surgery for
      colon cancer patients receiving chronic anti-thrombotic therapy (AT) remain
      unclear. METHODS: We identified 951 patients who underwent elective resection for
      colon cancer between 2009 and 2016 from our database. Patients were classified
      according to the surgical approach and chronic AT. Clinicopathological factors
      and surgical outcomes were analyzed between patient groups. Patients' backgrounds
      were matched using propensity scores in laparoscopic surgery. RESULTS: Anti
      thrombotic drugs were chronically used in 135 patients. Among 714 patients who
      underwent laparoscopy-assisted surgery, 96 received AT. The laparoscopic approach
      was superior to open surgery in terms of bleeding, surgical site infections, and
      hospital stay in patients receiving AT. In laparoscopy-assisted surgery, the AT
      group patients were older and showed lower hemoglobin and albumin levels than
      those not receiving AT (non-AT group), and were predominantly male. After
      propensity score matching, estimated blood loss and operative times were similar
      between the two groups (93 matched patients). The frequencies of postoperative
      bleeding (2.2%) and thrombotic complications (0%) in the AT group did not
      significantly differ from those in the non-AT group (1.1 and 0%, respectively).
      Moreover, AT did not affect survivals. CONCLUSION: Laparoscopic approach appears
      to be safer and beneficial for colonic cancer patients receiving long-term AT.
      Bleeding and thrombotic events associated with laparoscopic surgery were not
      significantly affected by AT.

PMID- 29340826
TI  - Single-port laparoscopic surgery in uncomplicated acute appendicitis: a
      randomized controlled trial.
AB  - BACKGROUND: Single-port laparoscopic surgery (SPLS) is an alternative, minimally
      invasive surgical approach for managing appendicitis. The aim of this randomized
      trial was to evaluate the safety and efficacy of SPLS in uncomplicated
      appendicitis. METHODS: Between December 2009 and November 2010, 194 patients with
      radiologically diagnosed acute appendicitis were randomly allocated to undergo
      either SPLS or multiport laparoscopic surgery (MPLS). Patients with
      intraoperative findings of perforated appendicitis were excluded from the
      analysis. The primary endpoint was perioperative morbidity. All data were
      analyzed according to the intention-to-treat principle. RESULTS: Fourteen cases
      were excluded from the analysis. Of the remaining 180 patients, 90 were assigned
      to the SPLS group, and 90 to the MPLS group. Baseline characteristics were well
      balanced between the groups. In the SPLS group, the rate of conversion to MPLS
      was 11.1%. The operation time was 14.5 min longer for SPLS than for MPLS (p <
      0.01), but there was no between-group difference in the rate of intraoperative
      complications (SPLS, 4.4%; MPLS, 0%; p = 0.12) or postoperative complications
      (SPLS, 4.4%; MPLS, 2.2%; p = 0.68). Compared to the MPLS group, the SPLS group
      had higher cumulative dose of analgesics (tramadol; 73.9 vs. 51.7 mg, p = 0.04),
      longer postoperative time to first passage of flatus (27.7 vs. 20.1 h, p < 0.01),
      longer postoperative hospitalization (2.5 vs. 2.1 days, p < 0.05), and higher
      total cost (1826.9 vs. 1662.4 USD, p < 0.01). CONCLUSIONS: This randomized trial
      indicates that, compared to MPLS, SPLS does not increase the rate of
      perioperative or postoperative complications in uncomplicated appendicitis, but
      may have disadvantages such as increased operation time, later postoperative
      functional recovery, longer hospital stay, and higher costs, although the
      difference is minimal (ClinicalTrials.gov Identifier: NCT01007318).

PMID- 29340827
TI  - Single-incision laparoscopic hepaticojejunostomy for children with perforated
      choledochal cysts.
AB  - BACKGROUND: Conventionally, perforated choledochal cyst (CDC) is a
      contraindication of laparoscopic treatment. The current study is to evaluate
      efficacy of single-incision laparoscopic hepaticojejunostomy (SILH) in children
      with perforated CDCs. METHODS: One hundred and thirty-three children with
      perforated CDCs who underwent SILHs in our hospital between August 2011 and
      August 2017 were reviewed. RESULTS: Fifteen (11.3%) patients were converted to
      open procedures due to severe adhesions and oozing. The mean age at SILH was 2.09
      years (range 2 days-12.37 years). The average operative time was 3.23 h (range 2
      5 h). The mean postoperative hospital stay was 6.25 days (range 4-16 days). The
      mean time to full diet resumption was 2.18 days (range 2-6 days). The mean
      duration of drainage was 3.71 days (range 3-10 days). The median follow-up period
      was 24 months. Postoperative liver function tests and serum amylase levels
      returned to normal within 1 year. Three (2.5%) patients required blood
      transfusions because of extensive oozing from intramural micro-vessels of CDCs.
      Two (1.7%) patients encountered duodenal injuries because of severe adhesions.
      The duodenum was repaired with double-layer 5-0 PDS running sutures. One (0.8%)
      patient with giant CDC had abdominal fluids because of extensive dissection of
      intrapancreatic segment of CDC. He recovered after 10 days of drainage. None of
      patients had bile leak, anastomotic stenosis, cholangitis, intrahepatic reflux,
      pancreatic leak, pancreatic calculi formation, pancreatitis, Roux-loop
      obstruction, or adhesive intestinal obstruction. CONCLUSIONS: Single-incision
      laparoscopic hepaticojejunostomy is safe and effective for selected patients with
      perforated CDCs in experienced hands.

PMID- 29340829
TI  - Trends and surgical outcomes of laparoscopic versus open pyloromyotomy.
AB  - BACKGROUND: Hypertrophic pyloric stenosis (HPS) is one of the most common
      pediatric illnesses necessitating surgical intervention. Controversy remains over
      the optimal surgical approach between laparoscopic pyloromyotomy (LP) and open
      pyloromyotomy (OP). LP has gained acceptance for management of HPS in an era of
      expanding minimal access surgical approaches to pediatric conditions. Several
      studies suggest advantages of LP over OP; however, selection bias and small
      sample sizes remain a concern. This study compares the outcomes of LP versus OP
      using propensity score methods. METHODS: The 2013-2015 ACS NSQIP Pediatric PUF
      was queried for all infants undergoing pyloromyotomy. The trend in the proportion
      of infants undergoing LP was described and perioperative outcomes between the OP
      and LP cohorts were compared using propensity score weighted regression models.
      RESULTS: 4847 infants were identified to have undergone surgical pyloromyotomy.
      The proportion of LP performed increased significantly from 59% in 2013 to 65.5%
      in 2015 (p < 0.001). LP was associated with lower overall complications (1.4% vs
      2.9%) (ORadj 0.52, 95% CI 0.34-0.80), surgical site-related complications (1.1%
      vs 2.1%) (ORadj 0.52, 95% CI 0.32-0.84), and post-operative length of stay (1.5
      days vs 1.9 days) (ORadj 0.89, 95% CI 0.81-0.98) without significant differences
      in related re-operation (0.9% vs 0.9%) (ORadj 1.01, 95% CI 0.52-1.93) or
      readmissions (1.4% vs 2.1%) (ORadj 0.73, 95% CI 0.46-1.17). CONCLUSIONS: Our
      study demonstrates that LP is increasingly utilized for management of
      hypertrophic pyloric stenosis and is associated with shorter length of stay, and
      lower odds of surgical site-specific and overall complications without
      differences in related re-operations. This study supports LP as a safe and
      effective method for management of HPS.

PMID- 29340830
TI  - Fabrication of SrGe2 thin films on Ge (100), (110), and (111) substrates.
AB  - Semiconductor strontium digermanide (SrGe2) has a large absorption coefficient in
      the near-infrared light region and is expected to be useful for multijunction
      solar cells. This study firstly demonstrates the formation of SrGe2 thin films
      via a reactive deposition epitaxy on Ge substrates. The growth morphology of
      SrGe2 dramatically changed depending on the growth temperature (300-700  degrees
      C) and the crystal orientation of the Ge substrate. We succeeded in obtaining
      single-oriented SrGe2 using a Ge (110) substrate at 500  degrees C. Development
      on Si or glass substrates will lead to the application of SrGe2 to high
      efficiency thin-film solar cells.

PMID- 29340828
TI  - Hiatal hernia recurrence following magnetic sphincter augmentation and posterior
      cruroplasty: intermediate-term outcomes.
AB  - BACKGROUND: We have previously reported short-term outcomes after hiatal hernia
      repair (HHR) at the time of magnetic sphincter augmentation (MSA) for
      gastroesophageal reflux disease (GERD). Here we report intermediate-term outcomes
      and hernia recurrence rate after concomitant MSA and HHR. METHODS: This is a
      retrospective cohort study of patients who underwent repair of a hiatal hernia 3
      cm or larger at the time of MSA implantation between May 2009 and December 2015.
      The primary endpoint was hiatal hernia recurrence identified by routine
      postoperative videoesophagography or endoscopy. Recurrence was defined by a 2 cm
      or greater upward displacement of the stomach through the diaphragmatic
      esophageal hiatus. Secondary endpoints included cessation of proton-pump
      inhibitor (PPI), persistent dysphagia requiring intervention, and GERD health
      related quality-of-life (HRQL) scores 1 year from surgery. RESULTS: During the
      study period, 47 of 53 (89%) patients underwent concomitant MSA with HHR and
      complied with surveillance. Hiatal hernias ranged from 3 to 7 cm (mean 4 +/- 1).
      Mean clinical follow-up time was 19 months (range 1-39). GERD-HRQL score
      decreased from 20.3 to 3.1 (p < .001), 89% of patients remained off PPIs, and 97%
      of patients reported improvement or resolution of symptoms. Two recurrent hiatal
      hernias were identified on surveillance imaging for a recurrence rate of 4.3% at
      a mean 18 (+/- 10) months after initial operation. Persistent dysphagia occurred
      in 13% (6/47) over the first year, which resolved after a single balloon dilation
      in 67% (4/6). Two patients elected for device removal due to dilation-refractory
      dysphagia and persistent reflux symptoms. CONCLUSION: Concomitant magnetic
      sphincter augmentation and hiatal hernia repair in patients with gastroesophageal
      reflux disease and a moderate-sized hiatal hernia demonstrates durable subjective
      reflux control and an acceptable hiatal hernia recurrence rate at 1- to 2-year
      follow-up.

PMID- 29340831
TI  - Noninvasive quantification of left-to-right shunt by phase contrast magnetic
      resonance imaging in secundum atrial septal defect: the effects of breath holding
      and comparison with invasive oximetry.
AB  - To investigate the effect of breath-holding on left-to-right shunts in patients
      with a secundum atrial septal defect (ASD). Thirty-five consecutive patients with
      secundum ASDs underwent right heart catheterization and invasive oximetry. Phase
      contrast magnetic resonance imaging (MRI) was performed for the main pulmonary
      artery and ascending aorta. All measurements were obtained during free breathing
      (FB) (quiet breathing; no breath-hold), expiratory breath-hold (EBH), and
      inspiratory breath-hold (IBH). Pulmonary circulation flow (Qp) and systemic
      circulation flow (Qs) were calculated by multiplying the heart rate by the stroke
      volume. Measurements during FB, EBH, and IBH were compared, and the differences
      compared to invasive oximetry were evaluated. There were significant differences
      among the measurements during FB, EBH, and IBH for Qp (FB, 7.70 +/- 2.68; EBH,
      7.18 +/- 2.34; IBH, 6.88 +/- 2.51 l/min); however, no significant difference was
      found for Qs (FB, 3.44 +/- 0.74; EBH, 3.40 +/- 0.83; IBH, 3.40 +/- 0.86 l/min).
      There were significant differences among the measurements during FB, EBH, and IBH
      for Qp/Qs (FB, 2.38 +/- 1.12; EBH, 2.24 +/- 0.95; IBH, 2.14 +/- 0.97). Qp/Qs
      during FB and EBH correlated better with Qp/Qs measured by invasive oximetry than
      did IBH. The limit of agreement was smaller for EBH than for FB and IBH. In
      patients with secundum ASDs, Qp/Qs significantly decreased with breath-holding.
      The accuracy of the Qp/Qs measurement by MRI compared with invasive oximetry
      during EBH was higher than during FB and IBH.

PMID- 29340832
TI  - Sacral neuromodulation in patients with congenital faecal incontinence. Special
      issues and review of the literature.
AB  - BACKGROUND: The aim of the present study was to evaluate the effectiveness of
      sacral neuromodulation (SNM) as a treatment for congenital faecal incontinence
      (FI). METHODS: A retrospective study was conducted on patients with congenital FI
      who had SNM surgery at our institution between October 2005 and June 2013. An
      initial percutaneous nerve evaluation was performed, and patients with an
      improvement of more than 50% in their symptoms had permanently implants for SNM
      treatment. RESULTS: There were 4 patients who received a permanent implant. Mean
      duration of follow-up was 67.5 months (range 45-135 months). At last follow-up, 2
      patients maintained significant improvement with SNM, 1 was explanted after 4
      years of treatment due to infection but remained asymptomatic and SNM failed in
      the remaining patient who went on to graciloplasty. CONCLUSIONS: SNM may be of
      value for treating FI in patients with anorectal malformations.

PMID- 29340833
TI  - Short-term outcomes of transanal haemorrhoidal dearterialization versus tissue
      selecting technique.

PMID- 29340834
TI  - Limited daily feeding and intermittent feeding have different effects on regional
      brain energy homeostasis during aging.
AB  - Albeit aging is an inevitable process, the rate of aging is susceptible to
      modifications. Dietary restriction (DR) is a vigorous nongenetic and
      nonpharmacological intervention that is known to delay aging and increase
      healthspan in diverse species. This study aimed to compare the impact of
      different restricting feeding regimes such as limited daily feeding (LDF, 60% AL)
      and intermittent feeding (IF) on brain energy homeostasis during aging. The
      analysis was focused on the key molecules in glucose and cholesterol metabolism
      in the cortex and hippocampus of middle-aged (12-month-old) and aged (24-month
      old) male Wistar rats. We measured the impact of different DRs on the expression
      levels of AMPK, glucose transporters (GLUT1, GLUT3, GLUT4), and the rate-limiting
      enzyme in the cholesterol synthesis pathway (HMGCR). Additionally, we assessed
      the changes in the amounts of cholesterol, its metabolite, and precursors
      following LDF and IF. IF decreased the levels of AMPK and pAMPK in the cortex
      while the increased levels were detected in the hippocampus. Glucose metabolism
      was more affected in the cortex, while cholesterol metabolism was more influenced
      in the hippocampus. Overall, the hippocampus was more resilient to the DRs, with
      fewer changes compared to the cortex. We showed that LDF and IF differently
      affected the brain energy homeostasis during aging and that specific brain
      regions exhibited distinct vulnerabilities towards DRs. Consequently, special
      attention should be paid to the DR application among elderly as different phases
      of aging do not respond equally to altered nutritional regimes.

PMID- 29340835
TI  - Repurposed FDA-approved drugs targeting genes influencing aging can extend
      lifespan and healthspan in rotifers.
AB  - Pharmaceutical interventions can slow aging in animals, and have advantages
      because their dose can be tightly regulated and the timing of the intervention
      can be closely controlled. They also may complement environmental interventions
      like caloric restriction by acting additively. A fertile source for therapies
      slowing aging is FDA approved drugs whose safety has been investigated. Because
      drugs bind to several protein targets, they cause multiple effects, many of which
      have not been characterized. It is possible that some of the side effects of
      drugs prescribed for one therapy may have benefits in retarding aging. We used
      computationally guided drug screening for prioritizing drug targets to produce a
      short list of candidate compounds for in vivo testing. We applied the virtual
      ligand screening approach FINDSITEcomb for screening potential anti-aging protein
      targets against FDA approved drugs listed in DrugBank. A short list of 31
      promising compounds was screened using a multi-tiered approach with rotifers as
      an animal model of aging. Primary and secondary survival screens and cohort life
      table experiments identified four drugs capable of extending rotifer lifespan by
      8-42%. Exposures to 1 uM erythromycin, 5 uM carglumic acid, 3 uM capecitabine,
      and 1 uM ivermectin, extended rotifer lifespan without significant effect on
      reproduction. Some drugs also extended healthspan, as estimated by mitochondria
      activity and mobility (swimming speed). Our most promising result is that rotifer
      lifespan was extended by 7-8.9% even when treatment was started in middle age.

PMID- 29340836
TI  - Primary culture of lung fibroblasts from hyperoxia-exposed rats and a
      proliferative characteristics study.
AB  - Lung fibrosis is an ultimate consequence of bronchopulmonary dysplasia (BPD)
      which shows the excessive proliferation of lung fibroblasts (LFs). To find a
      better model for studying the role of LFs in hyperoxia-induced lung fibrosis at
      the cellular level, we isolated LFs from the lung tissue of hyperoxia- and
      normoxia-exposed rat lungs on postnatal days 7, 14 and 21 for primary culture to
      study their proliferative behavior. In the present study, the LF predominance was
      > 95% in our culture method. The LFs isolated from rats exposed to hyperoxia in
      vivo showed significantly greater proliferation than that from normoxia-exposed
      rats. Flow cytometry revealed that percentage of LFs in S and G2/M stage
      increased, and proportion in the G0/G1 stage declined at the same time. A greater
      presence of myofibroblasts in LFs isolated from rats exposed to hyperoxia
      compared with those exposed to normoxia. In addition, elevated collagen level,
      transforming growth factor-beta and connective tissue growth factor protein
      expression in conditioned medium were also found in hyperoxia LFs. These data
      demonstrate that hyperoxia promotes LFs proliferation, myofibroblast
      transdifferentiation and collagen synthesis in a time-dependent manner. The
      primary culture of LFs from hyperoxia-exposed rats is a feasible method for
      studying the pathogenesis and treatment of lung fibrosis caused by BPD at the
      cellular level.

PMID- 29340837
TI  - Exacerbation of autoimmune hemolytic anemia induced by the first dose of
      programmed death-1 inhibitor pembrolizumab: a case report.
AB  - Immune checkpoint inhibitors (ICIs) have demonstrated efficacy against various
      types of cancers. In addition to immune-related adverse events (irAEs) induced by
      ICIs, exacerbation of baseline autoimmune disease has been occasionally reported.
      This is the first report of autoimmune hemolytic anemia (AIHA) exacerbated by
      pembrolizumab. An 82-year-old Japanese male was diagnosed with lung
      adenocarcinoma 2 years ago. The patient had chronic anemia with positive direct
      and indirect Coombs test prior to initiating pembrolizumab therapy at a nearby
      hospital. However, a definitive diagnosis of AIHA was not made at that time.
      Seventeen days after the first dose of pembrolizumab, the patient was admitted to
      the Kobe City Medical Center General Hospital with severe hemolytic anemia (Hb
      3.6 g/dL). After thorough examinations including bone marrow biopsy, the patient
      was diagnosed with pre-existing AIHA exacerbated by pembrolizumab therapy. Two
      weeks after treatment with prednisone, the levels of hemoglobin became stable
      with the reduced frequency of blood transfusion and improvements of hemolytic
      findings on blood tests and the patient was discharged from the hospital. This
      case report highlighted the importance of determining the patient's pre-existing
      autoimmune status associated with chronic anemia prior to initiating treatment
      with ICIs.

PMID- 29340838
TI  - Text-based phenotypic profiles incorporating biochemical phenotypes of inborn
      errors of metabolism improve phenomics-based diagnosis.
AB  - Phenomics is the comprehensive study of phenotypes at every level of biology:
      from metabolites to organisms. With high throughput technologies increasing the
      scope of biological discoveries, the field of phenomics has been developing rapid
      and precise methods to collect, catalog, and analyze phenotypes. Such methods
      have allowed phenotypic data to be widely used in medical applications, from
      assisting clinical diagnoses to prioritizing genomic diagnoses. To channel the
      benefits of phenomics into the field of inborn errors of metabolism (IEM), we
      have recently launched IEMbase, an expert-curated knowledgebase of IEM and their
      disease-characterizing phenotypes. While our efforts with IEMbase have realized
      benefits, taking full advantage of phenomics requires a comprehensive curation of
      IEM phenotypes in core phenomics projects, which is dependent upon contributions
      from the IEM clinical and research community. Here, we assess the inclusion of
      IEM biochemical phenotypes in a core phenomics project, the Human Phenotype
      Ontology. We then demonstrate the utility of biochemical phenotypes using a text
      based phenomics method to predict gene-disease relationships, showing that the
      prediction of IEM genes is significantly better using biochemical rather than
      clinical profiles. The findings herein provide a motivating goal for the IEM
      community to expand the computationally accessible descriptions of biochemical
      phenotypes associated with IEM in phenomics resources.

PMID- 29340839
TI  - The cumulative incidence and risk factors of postoperative inguinal hernia in
      patients undergoing radical prostatectomy.
AB  - BACKGROUND: The aim of this study is to investigate the cumulative incidence and
      risk factors of postoperative inguinal hernia (PIH) in patients undergoing
      radical prostatectomy, i.e., laparoscopic prostatectomy (LRP) and robot-assisted
      laparoscopic prostatectomy (RARP). METHODS: This study included 1124 patients who
      had undergone radical prostatectomy or transurethral resection of bladder tumor
      from 2011-2016. We compared the cumulative incidence of PIH in the radical
      prostatectomy groups (460; LRP 341, RARP 119) and the control group (664;
      transurethral resection of bladder tumor), and we then analyzed the risk factors
      (age, operative methods, previous abdominal operative history, thickness and
      width of external oblique muscle and rectus muscle, thickness of abdominal
      subcutaneous fat layer at Hesselbach's triangle level, body mass index, prostate
      specific antigen, operative time, specimen weight, Gleason score, and pathology T
      stage) of PIH in the radical prostatectomy groups. RESULTS: The median follow-up
      period in this study was 39.6 months. In Kaplan-Meier curve analysis, the
      cumulative incidence of PIH was 5.3, 4.2, and 0.5% for the LRP, RARP, and control
      groups, respectively (p < 0.001). Multiple logistic regressions showed that
      thickness of external oblique muscle and width of rectus muscle were significant
      risk factors (p < 0.001 and p = 0.027). CONCLUSIONS: PIH is considered to be one
      of the complications of LRP and RARP. Moreover, we suggest that if the thickness
      of the muscle is <7.3 mm, thoughtful surgical manipulation is needed for radical
      prostatectomy, and care should be taken to determine whether hernia occurs during
      follow-up.

PMID- 29340840
TI  - Application of gamma irradiation knowledge in tissue sterilisation: inactivation
      of malaria parasite.
AB  - Malaria is one of the exclusion criteria used in selecting tissue donors and the
      absence of this information can lead to rejection of tissues for transplant. The
      studies on the malaria parasite have been confined to low dose attenuation of
      parasites in blood for transfusion purposes. There is no published information
      relating to the inactivation of malaria parasites with irradiation for the
      sterilisation of tissues. A dose-surviving parasite population following
      radiation was replotted using D0 value from a published paper whereby D10 value
      of 41 Gy was obtained. Calculation of sterilisation dose for achieving SAL 10-6
      of malaria parasites demonstrated the effectiveness of the sterilisation dose of
      25 kGy being used in tissue banking.

PMID- 29340820
TI  - The development and validation of a scoring tool to predict the operative
      duration of elective laparoscopic cholecystectomy.
AB  - BACKGROUND: The ability to accurately predict operative duration has the
      potential to optimise theatre efficiency and utilisation, thus reducing costs and
      increasing staff and patient satisfaction. With laparoscopic cholecystectomy
      being one of the most commonly performed procedures worldwide, a tool to predict
      operative duration could be extremely beneficial to healthcare organisations.
      METHODS: Data collected from the CholeS study on patients undergoing
      cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used
      to study operative duration. A multivariable binary logistic regression model was
      produced in order to identify significant independent predictors of long (> 90
      min) operations. The resulting model was converted to a risk score, which was
      subsequently validated on second cohort of patients using ROC curves. RESULTS:
      After exclusions, data were available for 7227 patients in the derivation
      (CholeS) cohort. The median operative duration was 60 min (interquartile range 45
      85), with 17.7% of operations lasting longer than 90 min. Ten factors were found
      to be significant independent predictors of operative durations > 90 min,
      including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness
      and CBD diameter. A risk score was then produced from these factors, and applied
      to a cohort of 2405 patients from a tertiary centre for external validation. This
      returned an area under the ROC curve of 0.708 (SE = 0.013, p < 0.001), with the
      proportions of operations lasting > 90 min increasing more than eightfold from
      5.1 to 41.8% in the extremes of the score. CONCLUSION: The scoring tool produced
      in this study was found to be significantly predictive of long operative
      durations on validation in an external cohort. As such, the tool may have the
      potential to enable organisations to better organise theatre lists and deliver
      greater efficiencies in care.

PMID- 29340841
TI  - An efficient gene disruption method using a positive-negative split-selection
      marker and Agrobacterium tumefaciens-mediated transformation for Nomuraea rileyi.
AB  - Targeted gene disruption via Agrobacterium tumefaciens-mediated transformation
      (ATMT) and homologous recombination is the most common method used to identify
      and investigate the functions of genes in fungi. However, the gene disruption
      efficiency of this method is low due to ectopic integration. In this study, a
      high-efficiency gene disruption strategy based on ATMT and the split-marker
      method was developed for use in Nomuraea rileyi. The beta-glucuronidase (gus)
      gene was used as a negative selection marker to facilitate the screening of
      putative transformants. We assessed the efficacy of this gene disruption method
      using the NrCat1, NrCat4, and NrPex16 genes and found that the targeting
      efficiency was between 36.2 and 60.7%, whereas the targeting efficiency using
      linear cassettes was only 1.0-4.2%. The efficiency of negative selection assays
      was between 64.1 and 82.3%. Randomly selected deletion mutants exhibited a single
      copy of the hph cassette. Therefore, high-throughput gene disruption could be
      possible using the split-marker method and the majority of ectopic integration
      transformants can be eliminated using negative selection markers. This study
      provides a platform to study the function of genes in N. rileyi.

PMID- 29340842
TI  - Application of automated peritoneal dialysis in urgent-start peritoneal dialysis
      patients during the break-in period.
AB  - OBJECTIVE: Whether automated peritoneal dialysis (APD) is a feasible strategy for
      urgent-start peritoneal dialysis (PD) therapy during the break-in period remains
      unclear. This study was conducted to compare the efficacy as well as
      complications among three PD modes during the break-in period. METHODS: Ninety
      six patients treated with urgent-start PD after catheterization were
      retrospectively analyzed. Patients were divided into three groups, incremental
      continuous ambulatory PD (CAPD) group (n = 26); APD group (n = 42); and APD-CAPD
      group (n = 28). Clinical parameters at the end of the break-in period and 1 month
      after the initiation of PD treatment were collected and analyzed. RESULTS:
      Compared with the traditional incremental CAPD, APD and APD-CAPD were superior as
      they could effectively remove small-molecule uremic toxins and correct
      electrolyte imbalance (P < 0.05), while did not increase the incidence of early
      complications during the break-in period (P > 0.05). However, APD led to a
      significant decline in albumin and pre-albumin, as compared with APD-CAPD and
      CAPD (P < 0.05). A PD strategy consisting 6 days of APD and 3 days of CAPD showed
      a great advantage in preventing excessive protein loss. There were no significant
      differences in all tested biochemical parameters among the three groups at 1
      month after treatment (all P > 0.05). CONCLUSION: Application of APD for urgent
      start PD during the break-in period is feasible. A combination of APD and CAPD
      regimens seems to be a more reasonable mode.

PMID- 29340843
TI  - Phytoene production utilizing the isoprenoid biosynthesis capacity of
      Thermococcus kodakarensis.
AB  - Phytoene (C40H64) is an isoprenoid and a precursor of various carotenoids which
      are of industrial value. Archaea can be considered to exhibit a relatively large
      capacity to produce isoprenoids, as they are components of their membrane lipids.
      Here, we aimed to produce isoprenoids such as phytoene in the hyperthermophilic
      archaeon Thermococcus kodakarensis. T. kodakarensis harbors a prenyltransferase
      gene involved in the biosynthesis of farnesyl pyrophosphate and geranylgeranyl
      pyrophosphate, which are precursors of squalene and phytoene, respectively.
      However, homologs of squalene synthase and phytoene synthase, which catalyze
      their condensation reactions, are not found on the genome. Therefore, a
      squalene/phytoene synthase homolog from an acidothermophilic archaeon Sulfolobus
      acidocaldarius, Saci_1734, was introduced into the T. kodakarensis chromosome
      under the control of a strong promoter. Production of the Saci_1734 protein was
      confirmed in this strain, and the generation of phytoene was detected (0.08-0.75
      mg L-1 medium). We then carried out genetic engineering in order to increase the
      phytoene production yield. Disruption of an acetyl-CoA synthetase I gene involved
      in hydrolyzing acetyl-CoA, the precursor of phytoene, together with the
      introduction of a second copy of Saci_1734 led to a 3.4-fold enhancement in
      phytoene production.

PMID- 29340844
TI  - Comments on: insomnia, postpartum depression and estradiol in women after
      delivery.

PMID- 29340845
TI  - Dihydrotestosterone Treatment Accelerates Autograft Reversal Sciatic Nerve
      Regeneration in Rats.
AB  - Neuroactive steroids such as progesterone, testosterone, and their derivatives
      have been widely studied for their neuroprotective roles in the nervous system.
      Autologous nerve transplantation is considered as the gold standard repair
      technique when primary suture is impossible; nevertheless, this method is far
      from ideal. In this study, we aimed to explore the impact of dihydrotestosterone
      (DHT), a 5alpha-reduced derivative of testosterone, on the recovery of peripheral
      nerve injury treated with autologous nerve transplantation. Sprague-Dawley rats
      were subjected to a 10-mm right side sciatic nerve reversed autologous nerve
      transplantation and randomly divided into groups that received DHT or DHT +
      flutamide (an androgen receptor blocker) daily for 8 weeks after operation. Our
      results demonstrated that DHT could speed up the rate of axonal regeneration and
      increase the expression of myelin protein zero (P0) in autograft reversal sciatic
      nerves. Thus, our study provided new insights into improving the prognosis of
      patients with long gap peripheral nerve defects.

PMID- 29340846
TI  - Novel Isoforms of N16 and N19 Families Implicated for the Nacreous Layer
      Formation in the Pearl Oyster Pinctada fucata.
AB  - Although a wide variety of proteins and genes possibly related to the shell
      formation in bivalve have been identified, their functions have been only
      partially approved. We have recently performed deep sequencing of expressed
      sequence tags (ESTs) from the pearl oyster Pinctada fucata using a next
      generation sequencer, identifying a dozen of novel gene candidates which are
      possibly associated with the nacreous layer formation. Among the ESTs, we focused
      on three novel isoforms (N16-6, N16-7, and N19-2) of N16 and N19 families with
      reference to five known genes in the families and determined the full-length cDNA
      sequences of these isoforms. Reverse transcription-polymerase chain reaction
      revealed that N16-6 was expressed in gill, gonad, adductor muscle, and mantle,
      whereas N16-7 exclusively in mantle. N19-2 was expressed in all tissues examined.
      In situ hybridization demonstrated their regional expression in mantle and pearl
      sac, which well corresponded to those shown by EST analysis previously reported.
      Shells in the pearl oyster injected with dsRNAs of N16-7 and N19-2 showed
      abnormal surface appearance in the nacreous layer. Taken together, novel isoforms
      in N16 and N19 families shown in this study are essential to form the nacreous
      layer.

PMID- 29340847
TI  - Comparative analysis of aneurysm volume by different methods based on angiography
      and computed tomography angiography.
AB  - Endovascular treatment and prognosis of intracranial aneurysms are based on size
      and volume, which demand more accurate neuroimaging techniques. Aneurysm volume
      calculation is important to choose endovascular treatment modalities and packing
      density calculation. Of all these methods, it remains unknown which one is the
      most accurate to calculate aneurysm volume. The objective of this study is to
      compare the accuracy of three angiography-based versus three tomographic-based
      methods which calculate aneurysm volume. A retrospective study which included
      patients with ruptured and unruptured cerebral aneurysms diagnosed by angiogram
      and computed tomography angiography (CTA) was done. The accuracy of each method
      was assessed with an ellipsoid glass model of known volume, which helped us to
      adjust variation in volumetric measurements done with AngioSuite(c) and
      AngioCalc(c) softwares (based on angiographic and tomographic images), 3D
      rotational angiography and 3D-CTA (tridimensional computed tomography
      angiography), based on measurements of diameters such as maximal width and
      maximal height. Descriptive statistics, ANOVA for repetitive samples and t test
      were used. We included 89 patients (126 saccular intracraneal aneurysms).
      AngioSuite(c) software (angiography-based) showed more accuracy compared to other
      methods in our control model. The geometric system (AngioCalc) based on CTA
      images was statistically different from all other methods studied. AngioCalc (CTA
      based) demonstrated a significant difference compared with other methods hence,
      it may overestimate volume measurements. AngioSuite

PMID- 29340848
TI  - Validation of the Korean Munich Chronotype Questionnaire.
AB  - PURPOSE: The Munich Chronotype Questionnaire (MCTQ) assesses actual sleep-wake
      timing and has advantages compared to prior chronotype questionnaires in that it
      differentiates sleep-wake patterns between work days and free days and uses
      corrected mid-sleep time on free days after correcting for accumulated sleep debt
      over the week to categorize chronotype. The current study, we validated the
      Korean version of the MCTQ. METHODS: In this study, 310 participants (mean age =
      27.09 +/- 5.64; 78.1% females) completed the Korean version of the MCTQ. RESULTS:
      MCTQ parameters were significantly correlated with MEQ (Morningness-Eveningness
      Questionnaire) scores (?r? >= 0.48), and test-retest reliability was >= 0.72.
      Cutoff scores of 2.5%, which correlated to 2.36 and 8.57 mid-sleep times in our
      sample, showed the best convergence with MEQ when categorizing chronotype.
      CONCLUSIONS: Our study suggests that the MCTQ is a useful questionnaire in
      assessing chronotype in young adults.

PMID- 29340849
TI  - Risk factors associated with feline urolithiasis.
AB  - Urinary tract diseases are among the main reasons for consultation in veterinary
      clinics and hospitals. It affects animals of any age, breed and gender. Among the
      diseases that affect this system, urolithiasis is the second largest cause of
      clinical signs compatible with feline urinary tract disease. The term
      urolithiasis refers to the presence of uroliths in any region of the urinary
      tract, but it is more commonly seen in the bladder and urethra. Uroliths are
      classified based on the type of mineral present in their composition, therefore,
      quantitative and qualitative analyzes are important for a better therapeutic
      approach. The animals may suffer from the disease and be asymptomatic, or show
      nonspecific clinical signs, making the diagnosis difficult. The disease should
      not be seen as a single problem, but as a consequence of various disorders. As
      dietary, metabolic, genetic and infectious causes, as well as factors that
      potentiate the chance of development of uroliths such as breed, age, sex, age
      range, obesity, sedentary lifestyle, geographic region and climate. Thus, the
      knowledge of the factors that influence the formation of uroliths, as well as the
      understanding of the pathophysiology, are key elements for better alternatives of
      therapy and prevention. The recognition of these factors helps to identify
      susceptible populations, minimizing exposure and increasing the protection
      factors, which facilitates the diagnosis and treatment of patients with
      urolithiasis. The objective of this paper is to present the main risk factors
      involved in the formation of urinary lithiasis in felines.

PMID- 29340850
TI  - Drug-related problems among community-dwelling older adults in mainland China.
AB  - Background Little is known about the extent of drug-related problems (DRPs) in
      community-dwelling older adult patients with chronic diseases in mainland China.
      Setting A medication therapy review service at a community health center in
      Chongqing, China. Objective To identify and categorize DRPs along with
      pharmacists' recommendations in addressing the DRPs identified. Method The study
      was conducted between May 2015 and July 2016. A total of 102 community-dwelling
      older adults were included. MTR was carried out by clinical pharmacists. DRPs and
      pharmacotherapy recommendations were recorded and analyzed. Main outcome measure
      The number of drug-related problems and main problem categories. Results The
      average age of patients was 69.4 years. Patients took an average of 6.3
      medications. A total of 489 DRPs were identified (mean of 4.8 per patient). The
      most common category was under-treated (27.8%) followed by over- or under-dose
      (18.8%) and monitoring (17.8%). The number of medications taken was the
      significant associated factor for DRPs. Pharmacists made 526 recommendations to
      address the DRPs (mean of 1.1 recommendations per DRP). Primary care providers
      accepted 68.1% of these recommendations, and implemented 60.9% of them.
      Conclusion The prevalence of DRPs among studied patient population was high.
      Pharmacists may play a vital role in addressing the DRPs and optimize
      pharmacotherapy through MTR service located in community health centers.

PMID- 29340851
TI  - Comparison of antibiotic dosing recommendations for neonatal sepsis from
      established reference sources.
AB  - Background Incorrect dosing is the most frequent prescribing error in
      neonatology, with antibiotics being the most frequently prescribed medicines.
      Computer physician order entry and clinical decision support systems can create
      consistency contributing to a reduction of medication errors. Although evidence
      based dosing recommendations should be included in such systems, the evidence is
      not always available and subsequently, dosing recommendations mentioned in
      guidelines and textbooks are often based on expert opinion. Objective To compare
      dosage recommendations for antibiotics in neonates with sepsis provided by eight
      commonly used and well-established international reference sources. Setting An
      expert team from our Dutch tertiary care neonatal intensive care unit selected
      eight well-established international reference sources. Method Daily doses of the
      seven most frequently used antibiotics in the treatment of neonatal sepsis,
      classified by categories for birth weight and gestational age, were identified
      from eight well-respected reference sources in neonatology/pediatric infectious
      diseases. Main outcome measure Standardized average daily dosage. Results A
      substantial variation in dosage recommendations of antibiotics for neonatal
      sepsis between the reference sources was shown. Dosage recommendations of
      ampicillin, ceftazidime, meropenem and vancomycin varied more than
      recommendations for benzylpenicillin, cefotaxime and gentamicin. One reference
      source showed a larger variation in dosage recommendations in comparison to the
      average recommended daily dosage, compared to the other reference sources.
      Conclusion Antibiotic dosage recommendations for neonates with sepsis can be
      derived from important reference sources and guidelines. Further exploration to
      overcome variation in dosage recommendations is necessary to obtain standardized
      dosage regimens.

PMID- 29340852
TI  - A geochemical view into continental palaeotemperatures of the end-Permian using
      oxygen and hydrogen isotope composition of secondary silica in chert rubble
      breccia: Kaibab Formation, Grand Canyon (USA).
AB  - The upper carbonate member of the Kaibab Formation in northern Arizona (USA) was
      subaerially exposed during the end Permian and contains fractured and zoned chert
      rubble lag deposits typical of karst topography. The karst chert rubble has
      secondary (authigenic) silica precipitates suitable for estimating continental
      weathering temperatures during the end Permian karst event. New oxygen and
      hydrogen isotope ratios of secondary silica precipitates in the residual rubble
      breccia: (1) yield continental palaeotemperature estimates between 17 and 22 
      degrees C; and, (2) indicate that meteoric water played a role in the
      crystallization history of the secondary silica. The continental
      palaeotemperatures presented herein are broadly consistent with a global mean
      temperature estimate of 18.2  degrees C for the latest Permian derived from
      published climate system models. Few data sets are presently available that allow
      even approximate quantitative estimates of regional continental
      palaeotemperatures. These data provide a basis for better understanding the end
      Permian palaeoclimate at a seasonally-tropical latitude along the western
      shoreline of Pangaea.

PMID- 29340853
TI  - Do bioresorbable polyesters have antimicrobial properties?
AB  - Biodegradable and bioresorbable polyesters (BBPEs) are a widespread class of
      aliphatic polymers with a plethora of applications in the medical field. Some
      reports speculate that these polymers have intrinsic antibacterial activity as a
      consequence of their acidic degradation by-products. The release of organic acids
      as a result of the hydrolytic degradation of BBPEs in vivo and the resulting pH
      drop could be an effective inhibitor of the growth of pathogens in the local
      environment adjacent to BBPE-based devices. However, there is no clear and
      conclusive evidence in the literature concerning the antibacterial activity of
      BBPE to support or refute this hypothesis. In this communication we address this
      point through an assessment of the antibacterial properties of six well
      established commercially available BBPEs. Agar diffusion assays and optical
      density measurements at 600 nm were performed on all the polymer samples to
      characterize the growth of bacteria and any potential inhibition over an
      incubation period of 24 h. The results indicated that BBPEs do not possess an
      intrinsic and immediate antibacterial activity, which is consistent with the
      clear mismatch between the time-scales for bacterial growth and the rate of
      degradation of the polyesters.

PMID- 29340854
TI  - Therapeutic efficacy and safety of a 1927-nm fractionated thulium laser on
      pattern hair loss: an evaluator-blinded, split-scalp study.
AB  - Laser- or light-assisted therapies have been used to improve the perifollicular
      environment by upregulating the expression of growth factors and signaling
      molecules for hair restoration. The aim of our study was to preclinically and
      clinically evaluate the therapeutic efficacy and safety of a 1927-nm fractionated
      thulium laser on pattern hair loss (PHL). An in vivo hairless mouse study and an
      in vivo human skin environmental scanning electron microscopy (ESEM) study were
      performed with different power and energy settings. Thereafter, an evaluator
      blinded, split-scalp study was conducted to evaluate hair thickness and density
      in 10 PHL patients treated with 12 sessions of fractionated thulium laser
      treatment with or without post-laser treatment application of a growth factor
      containing (GF) solution. In in vivo hairless mouse skin, inverted cone-shaped
      zones of thulium laser-induced tissue coagulation (LITC) were noted immediately
      after treatment in the epidermis and upper to mid-dermis without remarkable
      ablative tissue injury. The ESEM study revealed round to oval-shaped zones of non
      ablative LITC on the surface of the stratum corneum of a human subject
      immediately after laser irradiation. In PHL patients, 12 sessions of thulium
      laser monotherapy at 1-week intervals resulted in significantly increased hair
      density and thickness. Post-laser treatment application of GF solution offered
      additional therapeutic efficacy by improving hair density and thickness on the
      split scalp. The use of a fractionated thulium laser with or without post-laser
      therapy application of GF solution to treat PHL elicited remarkable improvements
      in hair thickness and hair counts.

PMID- 29340855
TI  - The relationship between target joints and direct resource use in severe
      haemophilia.
AB  - OBJECTIVES: Target joints are a common complication of severe haemophilia. While
      factor replacement therapy constitutes the majority of costs in haemophilia, the
      relationship between target joints and non drug-related direct costs (NDDCs) has
      not been studied. METHODS: Data on haemophilia patients without inhibitors was
      drawn from the 'Cost of Haemophilia across Europe - a Socioeconomic Survey'
      (CHESS) study, a cost assessment in severe haemophilia A and B across five
      European countries (France, Germany, Italy, Spain, and the United Kingdom) in
      which 139 haemophilia specialists provided demographic and clinical information
      for 1285 adult patients. NDDCs were calculated using publicly available cost
      data, including 12-month ambulatory and secondary care activity: haematologist
      and other specialist consultant consultations, medical tests and examinations,
      bleed-related hospital admissions, and payments to professional care providers. A
      generalized linear model was developed to investigate the relationship between
      NDDCs and target joints (areas of chronic synovitis), adjusted for patient
      covariates. RESULTS: Five hundred and thirteen patients (42% of the sample) had
      no diagnosed target joints; a total of 1376 target joints (range 1-10) were
      recorded in the remaining 714 patients. Mean adjusted NDDCs for persons with no
      target joints were EUR 3134 (standard error (SE) EUR 158); for persons with one
      or more target joints, mean adjusted NDDCs were EUR 3913 (SE EUR 157; average
      mean effect EUR 779; p < 0.001). CONCLUSIONS: Our analysis suggests that the
      presence of one or more target joints has a significant impact on NDDCs for
      patients with severe haemophilia, ceteris paribus. Prevention and management of
      target joints should be an important consideration of managing haemophilia
      patients.

PMID- 29340856
TI  - Core point-of-care ultrasound curriculum: What does every anesthesiologist need
      to know?
AB  - Point-of-care ultrasound (POCUS) is becoming an integral part of anesthesia
      practice throughout the world. Despite the growing interest in POCUS among
      trainees and faculty, POCUS training is variable among universities across
      Canada. This suggests a need for curriculum development and standardization.
      International guidelines for Emergency Medicine and Critical Care have common
      frameworks and may be used as a reference to model anesthesia-specific curricula.
      The Royal College of Anaesthetists of the United Kingdom currently offers the
      only nationally approved POCUS curriculum for anesthesia and critical care
      trainees. Most curricula have in common a stepwise approach that consists of
      foundation of knowledge and skills and competency building through practice.
      Nevertheless, a significant variety of didactic modalities have been described,
      and online learning and simulation offer clear advantages. What constitutes the
      minimum number of studies necessary to achieve competence is still debated as are
      the most appropriate tools for assessment of POCUS competency.Availability of
      trained staff anesthesiologists remains a major limitation to curricula
      implementation in most centres. A National Curriculum should be modeled on the
      Competency By Design Approach, in line with the CanMEDS 2015 roles, and start
      with a focus on basic POCUS modalities and applications. Guidance for the
      training and certification of POCUS among practicing anesthesiologists is
      lacking.

PMID- 29340858
TI  - Critical care echocardiography: a certification pathway for advanced users.

PMID- 29340859
TI  - Comparative Proteomics of Chromium-Transformed Beas-2B Cells by 2D-DIGE and MALDI
      TOF/TOF MS.
AB  - Chromium (Cr) is a highly toxic, common heavy metal used in industrial
      production. There are two types of Cr in nature: hexavalent chromium (Cr(VI)) and
      chromium trichloride (Cr(III)). Cr(III) is involved in the metabolism of sugars
      and lipids, whereas Cr(VI) is absorbed through the respiratory tract and skin and
      generates free radicals that result in secondary toxicity. Cr(VI) leads to cancer
      in the occupational population and is therefore recognized as a human carcinogen
      by the International Agency for Research on Cancer. The specific mechanism
      underlying Cr-induced carcinogenesis is complex. In this study, two-dimensional
      fluorescence difference gel electrophoresis and matrix-assisted laser desorption
      ionization-time-of-flight/time-of-flight mass spectrometry-based techniques were
      performed to analyze differentially expressed proteins between Beas-2B human
      bronchial epithelial cells and Cr(VI)-transformed Beas-2B cells. Many
      differentially expressed proteins were identified in the cells after malignant
      transformation, including serine/threonine kinase 11, endothelial nitric oxide
      synthase 3, apolipoprotein A1, vinculin, and lamin A/C. These proteins are
      involved in many signaling and metabolic pathways, including apoptosis,
      autophagy, the PI3K/Akt signaling pathway, focal adhesion, cell motility, and
      actin cytoskeleton rearrangement.

PMID- 29340860
TI  - Trace element phytoextraction from contaminated soil: a case study under
      Mediterranean climate.
AB  - The current field study aims to assess the suitability of four different plant
      species (i.e. poplar, willow, hemp and alfalfa) to be used for trace element (TE)
      (i.e. Cd, Cu, Ni, Pb and Zn) phytoextraction under hot-arid Mediterranean climate
      conditions. Plants were grown for two consecutive years on a moderate TE
      contaminated soil, supplied with water and mineral nutrients. The growth and
      physiological parameters were assessed throughout the trial to compare the
      response of plants to the environmental pollution, and TE uptake rates were
      measured for aboveground plant tissues. The phytoextraction rate for each species
      was expressed as a function of aboveground biomass yield and the TE uptake and
      translocation within the plant. Alfalfa played a significant role in reducing
      extractable Ni (60.6%) and Zn (46%) in the soil, whereas hemp reduced 32% of
      extractable Cd and 46% of extractable Pb; poplar decreased extractable Cd (37%),
      Ni (49%), Pb (46%) and Zn (63%); and willow reduced the extractable Zn (73%)
      compared to the beginning of the trial. No change in total TE content was
      observed; however, poplar and willow were able to extract and accumulate the
      highest amount of Zn (3200 and 5200 g ha-1 year-1 respectively) and Cu (182 and
      116 g ha-1 year-1), whereas hemp, with 36 g ha-1 year-1, showed the best
      phytoextraction potential for Pb. Overall, we found a positive correlation
      between the phytoextraction rate and biomass yield, extractable TE concentration
      and translocation factor (TF) and a negative relationship with Ca concentration
      in the soil.

PMID- 29340861
TI  - Investigating the composition characteristics of dissolved and
      particulate/colloidal organic matter in effluent-dominated stream using
      fluorescence spectroscopy combined with multivariable analysis.
AB  - Fluorescence excitation-emission matrix (EEM) spectroscopy combined with
      principal component analysis (PCA) and parallel factor analysis (PARAFAC) were
      used to investigate the compositional characteristics of dissolved and
      particulate/colloidal organic matter and its correlations with nitrogen,
      phosphorus, and heavy metals in an effluent-dominated stream, Northern China. The
      results showed that dissolved organic matter (DOM) was comprised of fulvic-like,
      humic-like, and protein-like components in the water samples, and fulvic-like
      substances were the main fraction of DOM among them. Particulate/colloidal
      organic matter (PcOM) consisted of fulvic-like and protein-like matter. Fulvic
      like substances existed in the larger molecular form in PcOM, and they comprised
      a large amount of nitrogen and polar functional groups. On the other hand,
      protein-like components in PcOM were low in benzene ring and bound to heavy
      metals. It could be concluded that nitrogen, phosphorus, and heavy metals in
      effluent had an effect on the compositional characteristics of natural DOM and
      PcOM, which may deepen our understanding about the environmental behaviors of
      organic matter in effluent.

PMID- 29340862
TI  - Effect of brewery wastewater obtained from different phases of treatment plant on
      seed germination of chickpea (Cicer arietinum), maize (Zea mays), and pigeon pea
      (Cajanus cajan).
AB  - Brewing industry releases large quantities of wastewater after product
      generation. Brewery wastewater contains organic compounds which are biodegradable
      in nature. These biodegradable wastes can be recycled and reused and hence
      considered as suitable products for agriculture. But before using wastewater for
      agriculture, it is better to evaluate the phytotoxic effects of wastewater on
      crops. Hence, the main objective of this study is to evaluate the effects of
      brewery effluent on seed germination and growth parameters of selected crop
      species like chickpea (Cicer arietinum), maize (Zea mays), and pigeon pea
      (Cajanus cajan). Study comprised seven types of water treatments-tap water as
      control, diluted UASBR effluent (50% effluent + 50% distilled water): UASBR50,
      undiluted UASBR effluent: UASBR100, diluted TC effluent (50% effluent + 50%
      distilled water): ETP50,TC effluent without dilution: ETP100, 10% diluted reverse
      osmosis (RO10) reject (10% RO reject + 90% distilled water), and 25% diluted
      reverse osmosis(RO25) reject (25% RO reject + 75% distilled water) with three
      replications in completely randomized design. Germination test was performed in
      petri plates for 5 days. Parameters like germination percentage, germination rate
      index, seedling length, phytotoxicity index, seed vigor index, and biomass were
      calculated. All parameters decreased with increase in respective effluent
      concentration. Among all treatments, RO25 showed highest inhibitory effect on all
      three crops. Even though undiluted effluent of UASBR and ETP effluent showed
      positive effect on germination, seedling growth of three crops was promoted to
      the maximum by UASBR50 and ETP50. Hence, from the study, it was concluded that
      dilution of brewery effluent can be recommended before using it for irrigational
      purpose.

PMID- 29340863
TI  - Effects of urease and nitrification inhibitors on the soil mineral nitrogen
      dynamics and nitrous oxide (N2O) emissions on calcareous soil.
AB  - Urease inhibitors and nitrification inhibitors can reduce nitrogen (N) loss in
      agriculture soil. However, the effect of inhibitors on soil N2O emissions under
      the drip irrigation system remains unclear. A pot and a field experiment with two
      inhibitors were conducted to explore how inhibitors regulate soil nitrogen
      transformation and N2O emissions. In the pot experiment, three treatments
      included control, urea, and urea + N-(n-butyl)thiophosphoric triamide (NBPT,
      urease inhibitor). In the field experiment, three treatments included control,
      urea, and urea + NBPT + 2-chloro-6-(trichloromethyl)pyridine (nitrapyrin,
      nitrification inhibitor). The urease inhibition rate in the treatment of urea +
      NBPT was 27.5% at the 14th day of incubation (pot experiment), and NH4+-N was
      significantly decreased by 37-64% compared with urea alone treatment. In the
      field experiment, the nitrification inhibition rate in the treatment of urea +
      NBPT + nitrapyrin was 47.7 and 63.9% on the 3rd day after fertilization at the
      wheat heading and filling stages, respectively. Compared to urea treatment, NO3-
      N concentration in the double-inhibitor-added treatment was significantly
      decreased by 32 and 20% on the 5th day after fertilization at the heading and
      filling stages, respectively; N2O fluxes were also decreased by 30.9 and 33.3% at
      the two stages of wheat, respectively. In total, adding an inhibitor reduced N
      loss by 7.39 and 7.44% at the 14th and 35th day in the pot experiment and by
      10.53 and 6.65% at the two growing stages of wheat in the field experiment,
      respectively. Path and correlation analysis showed that N2O emissions were
      significantly correlated with soil NO3- in both pot and field experiments.

PMID- 29340864
TI  - Analysis of accumulation formation of sediment contamination in reservoirs after
      decades of running: a case study of nitrogen accumulation in Biliuhe Reservoir.
AB  - Sediment contamination is an important influencing factor for reservoir water
      quality. Investigations have shown that reservoirs are facing the risk of
      sediment contamination after running for several decades in China. This paper
      proposes that the accumulation of sediment contaminant is resulted from the
      difference between the input and output of contaminant. Further, an accumulation
      model of reservoir sediment nitrogen is established based on this theory. The
      calculation result of Biliuhe Reservoir shows that inflow rate of total nitrogen
      into the reservoir is 4521.47 t/a, the outflow rate is 1033.97 t/a, nitrogen
      removal by denitrification is 1465.81 t/a, and the accumulation rate is 1841.68
      t/a. The accumulation rate of total nitrogen is 77.84 t/a in water, 924.42 t/a in
      suspended solids, and 839.42 t/a in sediment. The accumulation of nitrogen
      resulted in the total nitrogen concentration in water increasing from 1.71 mg/L
      in 1995 to 3.78 mg/L in 2013, and that in sediment increasing from 779.10 mg/kg
      in 1993 to 2725.00 mg/kg in 2013. It is concluded that sediment contamination has
      the characteristics of significant accumulation trend, complex forms, and high
      security risks, which has been a hidden security risk for reservoirs after
      decades of running. Heterogeneity of the reservoir and complicated influencing
      factors of sediment contaminant accumulation should be concerned next.

PMID- 29340865
TI  - Design of a tripartite network for the prediction of drug targets.
AB  - Drug-target networks have aided in many target prediction studies aiming at drug
      repurposing or the analysis of side effects. Conventional drug-target networks
      are bipartite. They contain two different types of nodes representing drugs and
      targets, respectively, and edges indicating pairwise drug-target interactions. In
      this work, we introduce a tripartite network consisting of drugs, other bioactive
      compounds, and targets from different sources. On the basis of analog
      relationships captured in the network and so-called neighbor targets of drugs,
      new drug targets can be inferred. The tripartite network was found to have a
      stable structure and simulated network growth was accompanied by a steady
      increase in assortativity, reflecting increasing correlation between degrees of
      connected nodes leading to even network connectivity. Local drug environments in
      the tripartite network typically contained neighbor targets and revealed
      interesting drug-compound-target relationships for further analysis. Candidate
      targets were prioritized. The tripartite network design extends standard drug
      target networks and provides additional opportunities for drug target prediction.

PMID- 29340866
TI  - "In silico" study of the binding of two novel antagonists to the nociceptin
      receptor.
AB  - Antagonists of the nociceptin receptor (NOP) are raising interest for their
      possible clinical use as antidepressant drugs. Recently, the structure of NOP in
      complex with some piperidine-based antagonists has been revealed by X-ray
      crystallography. In this study, a multi-flexible docking (MF-docking) procedure,
      i.e. docking to multiple receptor conformations extracted by preliminary
      molecular dynamics trajectories, together with hybrid quantum mechanics/molecular
      mechanics (QM/MM) simulations have been carried out to provide the binding mode
      of two novel NOP antagonists, one of them selective (BTRX-246040, formerly named
      LY-2940094) and one non selective (AT-076), i.e. able to inactivate NOP as well
      as the classical u- k- and delta-opioid receptors (MOP KOP and DOP). According to
      our results, the pivotal role of residue D1303,32 (upper indexes are Ballesteros
      Weinstein notations) is analogous to that enlighten by the already known X-ray
      structures of opioid receptors: binding of the molecules are predicted to require
      a slight readjustment of the hydrophobic pocket (residues Y1313,33, M1343,36,
      I2195,43, Q2806,52 and V2836,55) in the orthosteric site of NOP, accommodating
      either the pyridine-pyrazole (BTRX-246040) or the isoquinoline (AT-076) moiety of
      the ligand, in turn allowing the protonated piperidine nitrogen to maximize
      interaction (salt-bridge) with residue D1303,32 of the NOP, and the aromatic head
      to be sandwiched in optimal pi-stacking between Y1313,33 and M1343,36. The QM/MM
      optimization after the MF-docking procedure has provided the more likely
      conformations for the binding to the NOP receptor of BTRX-246040 and AT-076,
      based on different pharmacophores and exhibiting different selectivity profiles.
      While the high selectivity for NOP of BTRX-246040 can be explained by
      interactions with NOP specific residues, the lack of selectivity of AT-076 could
      be associated to its ability to penetrate into the deep hydrophobic pocket of
      NOP, while retaining a conformation very similar to the one assumed by the
      antagonist JDTic into the K-opioid receptor. The proposed binding geometries fit
      better the binding pocket environment providing clues for experimental studies
      aimed to design selective or multifunctional opioid drugs.

PMID- 29340867
TI  - Photoluminescent and Thermoluminescent Studies of Dy3+ and Eu3+ Doped Y2O3
      Phosphors.
AB  - Eu3+ doped and Dy3+ codoped yttrium oxide (Y2O3) phosphors have been prepared
      using solid-state reaction technique (SSR). The prepared phosphors were
      characterized by X-ray diffractometer (XRD), energy dispersive X-ray (EDX)
      spectroscopy, scanning electron microscopy (SEM) and Fourier transforms infrared
      spectroscopy (FTIR) techniques. Photoluminescence (PL) and Thermoluminescence
      (TL) properties were studied in detail. PL emission spectra were recorded for
      prepared phosphors under excitation wavelength 254 nm, which show a high intense
      peak at 613 nm for Y2O3:Dy3+, Eu3+ (1:1.5 mol %) phosphor. The correlated color
      temperature (CCT) and CIE analysis have been performed for the synthesized
      phosphors. TL glow curves were recorded for Eu3+doped and Dy3+codoped phosphors
      to study the heating rate effect and dose response. The kinetic parameters were
      calculated using peak shape method for UV and gamma exposures through
      computerized glow curve deconvolution (CGCD) technique. The phosphors show second
      order kinetics and activation energies varying from 5.823 * 10- 1 to 18.608 * 10-
      1 eV.

PMID- 29340868
TI  - Recent Progress in Understanding the Mechanisms of Pain and Itch: the Second
      Special Issue.

PMID- 29340870
TI  - A Pilot Evaluation of the Rapid Response Program: A Home Based Family Therapy.
AB  - A pilot evaluation study of the implementation of the Rapid Response Program, a
      program utilizing the ecosystemic structural family therapy model, in a rural
      area of Pennsylvania was conducted. This approach was implemented in children's
      mental health to supplant a costly model of care that had not proven to break the
      cycle of dependency for children with severe behavioral problems and their
      families. Initial results show that the Rapid Response Program appears to improve
      problematic family patterns and children's behavioral problems. The study results
      are limited by small sample size; however, the outcomes suggest that the program
      warrants further study using a more rigorous research design with a larger
      sample.

PMID- 29340869
TI  - Intervention Effect of Repetitive TMS on Behavioral Adjustment After Error
      Commission in Long-Term Methamphetamine Addicts: Evidence From a Two-Choice
      Oddball Task.
AB  - Behavioral adjustment plays an important role in the treatment and relapse of
      drug addiction. Nonetheless, few studies have examined behavioral adjustment and
      its plasticity following error commission in methamphetamine (METH) dependence,
      which is detrimental to human health. Thus, we investigated the behavioral
      adjustment performance following error commission in long-term METH addicts and
      how it varied with the application of repetitive transcranial magnetic
      stimulation (rTMS) of the left dorsolateral prefrontal cortex (DLPFC). Twenty
      nine male long-term METH addicts (for > 3 years) were randomly assigned to high
      frequency (10 Hz, n = 15) or sham (n = 14) rTMS of the left DLPFC during a two
      choice oddball task. Twenty-six age-matched, healthy male adults participated in
      the two-choice oddball task pretest to establish normal performance for
      comparison. The results showed that 10 Hz rTMS over the left DLPFC significantly
      decreased the post-error slowing effect in response times of METH addicts. In
      addition, the 10 Hz rTMS intervention remarkably reduced the reaction times
      during post-error trials but not post-correct trials. While the 10 Hz rTMS group
      showed a more pronounced post-error slowing effect than the healthy participants
      during the pretest, the post-error slowing effect in the posttest of this sample
      was similar to that in the healthy participants. These results suggest that high
      frequency rTMS over the left DLPFC is a useful protocol for the improvement of
      behavioral adjustment after error commission in long-term METH addicts.

PMID- 29340871
TI  - Neurotoxicity of Prosopis juliflora: from Natural Poisoning to Mechanism of
      Action of Its Piperidine Alkaloids.
AB  - Prosopis juliflora was introduced in northeastern Brazil in the 1940s, and since
      then, it has been available as an alternative for animal nutrition. However, the
      consumption of P. juliflora as main or sole source of food causes an illness in
      animals known locally as "cara torta" disease. Cattle and goats experimentally
      intoxicated presents neurotoxic damage in the central nervous system. Histologic
      lesions were mainly characterized by vacuolation and loss of neurons in
      trigeminal motor nuclei. Furthermore, mitochondrial damage in neurons and gliosis
      was reported in trigeminal nuclei of intoxicated cattle. Studies, using neural
      cell cultures, have reproduced the main cellular alterations visualized in cara
      torta disease and contributed to understanding the mechanism of action piperidine
      alkaloids, the main neurotoxic compound in P. juliflora leaves and pods. Here, we
      will present aspects of the biological and toxicological properties of P.
      juliflora and its pharmacologically active compounds.

PMID- 29340872
TI  - Abstracts of the 2017 A-CURE Symposium.

PMID- 29340874
TI  - Lattice Boltzmann simulations of droplet dynamics in time-dependent flows.
AB  - We study the deformation and dynamics of droplets in time-dependent flows using
      3D numerical simulations of two immiscible fluids based on the lattice Boltzmann
      model (LBM). Analytical models are available in the literature, which assume the
      droplet shape to be an ellipsoid at all times (P.L. Maffettone, M. Minale, J. Non
      Newton. Fluid Mech 78, 227 (1998); M. Minale, Rheol. Acta 47, 667 (2008)). Beyond
      the practical importance of using a mesoscale simulation to assess "ab initio"
      the robustness and limitations of such theoretical models, our simulations are
      also key to discuss --in controlled situations-- some relevant phenomenology
      related to the interplay between the flow time scales and the droplet time scales
      regarding the "transparency" transition for high enough shear frequencies for an
      external oscillating flow. This work may be regarded as a step forward to discuss
      extensions towards a novel DNS approach, describing the mesoscale physics of
      small droplets subjected to a generic hydrodynamical strain field, possibly
      mimicking the effect of a realistic turbulent flow on dilute droplet suspensions.

PMID- 29340873
TI  - Fontan Surgical Planning: Previous Accomplishments, Current Challenges, and
      Future Directions.
AB  - The ultimate goal of Fontan surgical planning is to provide additional insights
      into the clinical decision-making process. In its current state, surgical
      planning offers an accurate hemodynamic assessment of the pre-operative
      condition, provides anatomical constraints for potential surgical options, and
      produces decent post-operative predictions if boundary conditions are similar
      enough between the pre-operative and post-operative states. Moving forward,
      validation with post-operative data is a necessary step in order to assess the
      accuracy of surgical planning and determine which methodological improvements are
      needed. Future efforts to automate the surgical planning process will reduce the
      individual expertise needed and encourage use in the clinic by clinicians. As
      post-operative physiologic predictions improve, Fontan surgical planning will
      become an more effective tool to accurately model patient-specific hemodynamics.

PMID- 29340875
TI  - Thromboelastography-based anticoagulation management during extracorporeal
      membrane oxygenation: a safety and feasibility pilot study.
AB  - BACKGROUND: There is no consensus on the management of anticoagulation during
      extracorporeal membrane oxygenation (ECMO). ECMO is currently burdened by a high
      rate of hemostatic complications, possibly associated with inadequate monitoring
      of heparin anticoagulation. This study aims to assess the safety and feasibility
      of an anticoagulation protocol for patients undergoing ECMO based on
      thromboelastography (TEG) as opposed to an activated partial thromboplastin time
      (aPTT)-based protocol. METHODS: We performed a multicenter, randomized,
      controlled trial in two academic tertiary care centers. Adult patients with acute
      respiratory failure treated with veno-venous ECMO were randomized to manage
      heparin anticoagulation using a TEG-based protocol (target 16-24 min of the R
      parameter, TEG group) or a standard of care aPTT-based protocol (target 1.5-2 of
      aPTT ratio, aPTT group). Primary outcomes were safety and feasibility of the
      study protocol. RESULTS: Forty-two patients were enrolled: 21 were randomized to
      the TEG group and 21 to the aPTT group. Duration of ECMO was similar in the two
      groups (9 (7-16) days in the TEG group and 11 (4-17) days in the aPTT group, p =
      0.74). Heparin dosing was lower in the TEG group compared to the aPTT group (11.7
      (9.5-15.3) IU/kg/h vs. 15.7 (10.9-21.3) IU/kg/h, respectively, p = 0.03). Safety
      parameters, assessed as number of hemorrhagic or thrombotic events and
      transfusions given, were not different between the two study groups. As for the
      feasibility, the TEG-based protocol triggered heparin infusion rate adjustments
      more frequently (p < 0.01) and results were less frequently in the target range
      compared to the aPTT-based protocol (p < 0.001). Number of prescribed TEG or aPTT
      controls (according to study groups) and protocol violations were not different
      between the study groups. CONCLUSIONS: TEG seems to be safely used to guide
      anticoagulation management during ECMO. Its use was associated with the
      administration of lower heparin doses compared to a standard of care aPTT-based
      protocol. Trial registration ClinicalTrials.gov, October 22,2014. Identifier:
      NCT02271126.

PMID- 29340876
TI  - Biomaterials and Regenerative Medicine in Urology.
AB  - Autologous gastrointestinal tissue is the gold standard biomaterial for urinary
      tract reconstruction despite its long-term neuromechanical and metabolic
      complications. Regenerative biomaterials have been proposed as alternatives;
      however many are limited by a poor host derived regenerative response and
      deficient supportive elements for effective tissue regeneration in vivo.
      Urological biomaterials are sub-classified into xenogenic extracellular matrices
      (ECMs) or synthetic polymers. ECMs are decellularised, biocompatible,
      biodegradable biomaterials derived from animal organs. Synthetic polymers vary in
      chemical composition but may have the benefit of being reliably reproducible from
      a manufacturing perspective. Urological biomaterials can be 'seeded' with
      regenerative stem cells in vitro to create composite biomaterials for grafting in
      vivo. Mesenchymal stem cells are advantageous for regenerative purposes as they
      self-renew, have long-term viability and possess multilineage differentiation
      potential. Currently, tissue-engineered biomaterials are developing rapidly in
      regenerative urology with many important clinical milestones achieved. To truly
      translate from bench to bedside, regenerative biomaterials need to provide better
      clinical outcomes than current urological tissue replacement strategies.

PMID- 29340877
TI  - Brief Report: Subjective Social Mobility and Depressive Symptoms in Syrian
      Refugees to Germany.
AB  - Previous findings indicate that refugees are at increased risk for mental health
      problems. In addition to stressful pre-migration experiences, post-migration
      factors may contribute to poor mental health outcomes. Among immigrants to the
      United States, downward mobility in subjective social status (SSS) was associated
      with depression, corroborating the potentially detrimental mental health
      consequences of a decline in one's perceived social position. The present study
      examined whether downward mobility in SSS among male refugees from Syria to
      Germany is associated with depression. We found that refugees who experience
      stronger downward mobility in SSS exhibit more severe depressive symptoms and
      were more likely to fulfill provisional DSM-IV criteria for a diagnosis of Major
      Depression. Our findings highlight the importance to consider the 'social pain'
      of downward social mobility during the post-migration phase.

PMID- 29340878
TI  - Core curriculum case illustration: tubo-ovarian abscess.
AB  - This is the 47th installment of a series that will highlight one case per
      publication issue from the bank of cases available online as part of the American
      Society of Emergency Radiology (ASER) educational resources. Our goal is to
      generate more interest in and use of our online materials. To view more cases
      online, please visit the ASER Core Curriculum and Recommendations for Study
      online at: http://www.erad.org/page/CCIP_TOC .

PMID- 29340880
TI  - GATA-3 is superior to GCDFP-15 and mammaglobin to identify primary and metastatic
      breast cancer.
AB  - PURPOSE: Despite numerous studies on the utility of GATA-3 as breast cancer
      marker, its comparison with other breast markers, its concordance between primary
      and metastatic tumors and its expression in primary cancers from sites with
      frequent breast metastases remains unclear. METHODS: To address these questions,
      totally 993 invasive breast cancers (IBC), 254 paired nodal metastases, 23
      distant metastases, and 208 lung carcinomas were included. GATA-3 expression was
      analyzed by immunohistochemistry and compared to other breast markers [gross
      cystic disease fluid protein 15 (GCDFP-15) and mammaglobin (MGB)]. RESULTS: GATA
      3 was expressed in 82.5% of IBC, predominantly in luminal (93.9%), and lower in
      non-luminal cancers [59.6% of HER2 overexpressing (HER2-OE) and 38.1% of triple
      negative breast cancer (TNBC) subtypes]. GATA-3 identified more IBC than GCDFP-15
      (23.9%) and MGB (46.6%). However, MGB showed a comparable sensitivity for non
      luminal cancers to GATA-3. Combining MGB and GATA-3 improved sensitivity for both
      HER2-OE (80.8%) and TNBC cases (55.4%). GATA-3 showed a high sensitivity for
      nodal metastases and distant metastases, with good concordance with primary
      tumors. GATA-3 was expressed in 1.0% of lung carcinomas, with sensitivity and
      specificity of 82.5 and 99.0% in differentiating IBC and lung carcinoma.
      CONCLUSIONS: GATA-3 expression was the highest in luminal breast carcinomas, and
      showed higher sensitivity than GCDFP-15 and MGB. However, in the poorly
      differentiated IBC, its utility was still limited. One should be aware of the
      possible GATA-3 expression in lung carcinomas.

PMID- 29340879
TI  - Diethylstilbestrol arrested spermatogenesis and somatic growth in the juveniles
      of yellow catfish (Pelteobagrus fulvidraco), a fish with sexual dimorphic growth.
AB  - In fish, spermatogenesis and somatic growth are mainly regulated by hypothalamic
      pituitary-gonadal (HPG) and hypothalamic-pituitary-somatic (HPS) axes,
      respectively. Xenoestrogens have been reported to impair spermatogenesis in some
      fishes, and arrest somatic growth in some others, whereas, whether xenoestrogens
      are capable of disrupting spermatogenesis and somatic growth simultaneously in
      fish that exhibits sexual dimorphic growth is little known, and the underlying
      mechanisms remain poorly understood. In this study, male juveniles of yellow
      catfish (Pelteobagrus fulvidraco), which exhibits a sexual dimorphic growth that
      favors males, were exposed to diethylstilbestrol (DES) for 28 days. After
      exposure, DES significantly disrupted the spermatogenesis (decreased gonadal
      somatic index (GSI) and germ cell number) and arrested the somatic growth
      (declined body weight) of the catfish juveniles. Gene expression and plasma
      steroid analyses demonstrated the suppressed mRNA levels of genes in HPG axis
      (gnrh-II, fshbeta, and lhbeta in the brain and dmrt1, sf1, fshr, cyp17a1,
      cyp19a1a, and cyp11b2 in the testis) and decreased 17beta-estrodial (E2) and 11
      ketotestosterone (11-KT) levels in plasma. Further analysis revealed the arrested
      germ cell proliferation (cyclin d1), meiosis (dmc1, sycp3), and enhanced
      apoptosis (decreased bcl-2 and elevated bax/bcl-2 ratio) in the testis. Besides,
      DES also suppressed the mRNA levels of genes in HPS axis (ghrh, gh, and prl in
      the brain and ghr, igf1, igf2a, and igf2b in the liver). The suppressed HPG and
      HPS axes were thus supposed to disturb spermatogenesis and arrest somatic growth
      in yellow catfish. The present study greatly extended our understanding on the
      mechanisms underlying the toxicity of DES on spermatogenesis and somatic growth
      of fish.

PMID- 29340881
TI  - Circulating free DNA integrity and concentration as independent prognostic
      markers in metastatic breast cancer.
AB  - PURPOSE: Non-invasive blood-based molecular markers have been investigated for
      cancer diagnosis and prognosis. Circulating free or cell-free DNA (cfDNA)
      variables have been shown to be putative markers in breast cancer prognosis.
      METHODS: Here, we investigated the potential prognostic ability of cfDNA
      concentration and cfDNA integrity (cfDI) in a study cohort of 268 patients by
      quantitative PCR. We compared cfDNA concentration and cfDI at baseline and after
      one cycle of therapy in metastatic breast cancer (MBC) patients. RESULTS: A
      significantly increased cfDI (P = 1.21E-7 for ALU and P = 1.87E-3 for LINE1) and
      decreased cfDNA concentration (P = 1.17E-3 for ALU and P = 1.60E-2 for LINE1) in
      both repetitive DNA elements after one cycle of therapy was observed. A multiple
      Cox regression model indicated that cfDI and cfDNA concentration can serve as
      independent prognostic markers in patients at baseline with HR (95% CI) of 0.70
      (0.48-1.01) for ALU cfDI, 0.63 (0.44-0.92) for LINE1 cfDI, 2.44 (1.68-3.53) for
      ALU cfDNA concentration, and 2.12 (1.47-3.06) for LINE1 cfDNA concentration and
      after one cycle of therapy with HR (95% CI) of 0.59 (0.42-0.84) for ALU cfDI,
      0.51 (0.36-0.74) for LINE1 cfDI, 1.59 (1.31-1.92) for ALU cfDNA concentration,
      and 1.30 (1.17-1.45) for LINE1 cfDNA concentration, respectively. By comparing
      integrated prediction error of different models, cfDNA variables were shown to
      improve the prognostic power of the CTC status. CONCLUSIONS: We hereby show that
      cfDNA variables, especially in combination with other markers, can serve as
      attractive prognostic markers for MBC patients at baseline and during the
      systematic therapy.

PMID- 29340882
TI  - Circulating small-sized endothelial microparticles as predictors of clinical
      outcome after chemotherapy for breast cancer: an exploratory analysis.
AB  - PURPOSE: Therapeutic exploitation of angiogenesis in breast cancer has been
      limited by the lack of reliable biomarkers. Circulating small-sized endothelial
      microparticles (sEMP) are likely to play a significant role as messengers of
      angiogenesis. Higher levels of EMP have been observed in cancer patients, but
      their prognostic value in breast cancer is unknown. Our aim was to determine the
      value of circulating sEMP as a marker of response to chemotherapy in breast
      cancer. METHODS: We included patients with breast cancer treated with neoadjuvant
      or first-line chemotherapy. Baseline and post-treatment circulating sEMP (CD144+)
      were quantified using a flow cytometer approach specifically designed for
      analysis of small-sized particles (0.1-0.5 MUm). Small-sized EMP response was
      defined as a post-treatment decrease of sEMP larger than the median decrease of
      sEMP after chemotherapy. Baseline and post-chemotherapy VEGFA levels were
      determined with ELISA. RESULTS: Forty-four breast cancer patients were included
      (19 with metastatic and 25 with locally advanced disease). Median levels of sEMP
      decreased after chemotherapy (P = 0.005). Response to chemotherapy showed a non
      significant trend to associate with sEMP response (P = 0.056). A sEMP response
      was observed in 51% of patients and was associated with better overall survival
      (HR 0.18; 95% CI 0.04-0.87; P = 0.02) and progression free survival (HR 0.30; 95%
      CI 0.09-0.99; P = 0.04) in the group of women with metastatic disease. Post
      chemotherapy decrease of VEGFA levels was not associated with breast cancer
      prognosis. CONCLUSIONS: Our results did not support sEMP as a marker of response
      to chemotherapy. However, our exploratory analysis suggests that in patients with
      metastatic breast cancer, the decrease of sEMP levels after chemotherapy is
      associated with better overall and disease free survival and might be superior to
      VEGFA levels as an angiogenesis-related prognostic marker.

PMID- 29340883
TI  - Associations of coffee consumption and caffeine intake with mammographic breast
      density.
AB  - PURPOSE: Previous studies suggest that coffee and caffeine intake may be
      associated with reduced breast cancer risk. We investigated the association of
      coffee and caffeine intake with mammographic breast density by woman's menopausal
      status and, in postmenopausal women, by hormone therapy (HT). METHODS: This study
      included 4130 cancer-free women within the Nurses' Health Study and Nurses'
      Health Study II cohorts. Percent breast density (PD) was measured from digitized
      film mammograms using a computer-assisted thresholding technique and square root
      transformed for the analysis. Average cumulative coffee/caffeine consumption was
      calculated using data from all food frequency questionnaires preceding the
      mammogram date. Information regarding breast cancer risk factors was obtained
      from questionnaires closest to the mammogram date. We used generalized linear
      regression to quantify associations of regular, decaffeinated, and total coffee,
      and energy-adjusted caffeine intake with percent density. RESULTS: In
      multivariable analyses, decaffeinated coffee was positively associated with PD in
      premenopausal women (2+ cups/day: beta = 0.23, p trend = 0.03). In postmenopausal
      women, decaffeinated and total coffee were inversely associated with PD
      (decaffeinated 2+ cups/day: beta = - 0.24, p trend = 0.04; total 4+ cups/day:
      beta = - 0.16, p trend = 0.02). Interaction of decaffeinated coffee with
      menopausal status was significant (p-interaction < 0.001). Among current HT
      users, regular coffee and caffeine were inversely associated with PD (regular
      coffee 4+ cups/day: beta = - 0.29, p trend = 0.01; caffeine 4th vs. 1st quartile:
      beta = - 0.32, p trend = 0.01). Among past users, decaffeinated coffee was
      inversely associated with PD (2+ cups/day beta = - 0.70, p trend = 0.02).
      CONCLUSIONS: Associations of decaffeinated coffee with percent density differ by
      woman's menopausal status. Associations of regular coffee and caffeine with
      percent density may differ by HT status.

PMID- 29340884
TI  - "I would like to discuss it further with an expert": a focus group study of
      Finnish adults' perspectives on genetic secondary findings.
AB  - Lowered costs of genomic sequencing facilitate analyzing large segments of
      genetic data. Ethical debate has focused on whether and what kind of incidental
      or secondary findings (SFs) to report, and how to obtain valid informed consent.
      However, people's support needs after receiving SFs have received less attention.
      We explored Finnish adults' perspectives on reporting genetic SFs. In this
      qualitative study which included four focus group discussions (N = 23) we used
      four vignette letters, each reporting a genetic SF predisposing to a different
      disease: familial hypercholesterolemia, long QT syndrome, Lynch syndrome, and Li
      Fraumeni syndrome. Transcribed focus group discussions were analyzed using
      inductive thematic analysis. Major themes were immediate shock, dealing with
      worry and heightened risk, fear of being left alone to deal with SFs, disclosing
      to family, and identified support needs. Despite their willingness to receive
      SFs, participants were concerned about being left alone to deal with them.
      Empathetic expert support and timely access to preventive care were seen as
      essential to coping with shock and worry, and disclosing SFs to family.
      Discussion around SFs needs to concern not only which findings to report, but
      also how healthcare systems need to prepare for providing timely access to
      preventive care and support for individuals and families.

PMID- 29340885
TI  - Quantifying Diastolic Function: From E-Waves as Triangles to Physiologic Contours
      via the 'Geometric Method'.
AB  - Conventional echocardiographic diastolic function (DF) assessment approximates
      transmitral flow velocity contours (Doppler E-waves) as triangles, with peak
      (Epeak), acceleration time (AT), and deceleration time (DT) as indexes. These
      metrics have limited value because they are unable to characterize the underlying
      physiology. The parametrized diastolic filling (PDF) formalism provides a
      physiologic, kinematic mechanism based characterization of DF by extracting
      chamber stiffness (k), relaxation (c), and load (x o ) from E-wave contours. We
      derive the mathematical relationship between the PDF parameters and Epeak, AT, DT
      and thereby introduce the geometric method (GM) that computes the PDF parameters
      using Epeak, AT, and DT as input. Numerical experiments validated GM by analysis
      of 208 E-waves from 31 datasets spanning the full range of clinical diastolic
      function. GM yielded indistinguishable average parameter values per subject vs.
      the gold-standard PDF method (k: R2 = 0.94, c: R2 = 0.95, x o : R2 = 0.95, p <
      0.01 all parameters). Additionally, inter-rater reliability for GM-determined
      parameters was excellent (k: ICC = 0.956 c: ICC = 0.944, x o : ICC = 0.993).
      Results indicate that E-wave symmetry (AT/DT) may comprise a new index of DF. By
      employing indexes (Epeak, AT, DT) that are already in standard clinical use the
      GM capitalizes on the power of the PDF method to quantify DF in terms of
      physiologic chamber properties.

PMID- 29340886
TI  - Use of Kerrison Rongeur for safe and effective removal of bone in
      temporomandibular joint ankylosis.

PMID- 29340888
TI  - Wet Cupping Therapy Improves Local Blood Perfusion and Analgesic Effects in
      Patients with Nerve-Root Type Cervical Spondylosis.
AB  - OBJECTIVE: To observe wet cupping therapy (WCT) on local blood perfusion and
      analgesic effects in patients with nerve-root type cervical spondylosis (NT-CS).
      METHODS: Fifty-seven NT-CS patients were randomly divided into WCT group and
      Jiaji acupoint-acupuncture (JA) group according a random number table. WCT group
      (30 cases) was treated with WCT for 10 min, and JA group (27 cases) was treated
      with acupuncture for 10 min. The treatment efficacies were evaluated with a
      Visual Analogue Scale (VAS). Blood perfusion at Dazhui (GV 14) and Jianjing (GB
      21) acupoints (affected side) was observed with a laser speckle flowmetry, and
      its variations before and after treatment in both groups were compared as well.
      RESULTS: In both groups, the VAS scores significantly decreased after the
      intervention (P<0.01), while the blood perfusion at the two acupoints
      significantly increased after intervention (P<0.05); however, the increasement
      magnitude caused by WCT was obvious compared with JA (P<0.05). CONCLUSIONS: WCT
      could improve analgesic effects in patients with NT-CS, which might be related to
      increasing local blood perfusion of acupunct points.

PMID- 29340887
TI  - Toward Evidence-Based Chinese Medicine: Status Quo, Opportunities and Challenges.
AB  - How to test the treatments of Chinese medicine (CM) and make them more widely
      accepted by practitioners of Western medicine and the international healthcare
      community is a major concern for practitioners and researchers of CM. For
      centuries, various approaches have been used to identify and measure the efficacy
      and safety of CM. However, the high-quality evidence related to CM that produced
      in China is still rare. Over the recent years, evidence-based medicine (EBM) has
      been increasingly applied to CM, strengthening its theoretical basis. This paper
      reviews the past and present state of CM, analyzes the status quo, challenges and
      opportunities of basic research, clinical trials, systematic reviews, clinical
      practice guidelines and clinical pathways and evidence-based education developed
      or conducted in China, pointing out how EBM can help to make CM more widely used
      and recognized worldwide.

PMID- 29340889
TI  - Quantification of Myocardial Perfusion Defect Size in Rats: Comparison between
      Quantitative Perfusion SPECT and Autoradiography.
AB  - PURPOSE: Ultra-high resolution single-photon emission computed tomography (SPECT)
      system, using multiple pinhole collimators, has been applied to the imaging of
      small rodents. We aimed to compare the myocardial infarction (MI) area on
      quantitative perfusion single-photon emission computed tomography (QPS; Cedars
      Sinai Medical Center, USA) with that on high-resolution autoradiography in rat
      model to determine the accuracy of perfusion defect measurement by QPS.
      PROCEDURES: After thoracotomy, rats (n = 9) had their left coronary arteries
      occluded and reperfused before injection with 185 MBq [99mTc]
      methoxyisobutylisonitrile ([99mTc]MIBI) for SPECT and autoradiography. Healthy
      rats (n = 28) were similarly scanned to create a normal database on which to base
      QPS. The MI area on SPECT images was analysed automatically by QPS software. For
      the autoradiography images, regions of interest for MI were set at 1 mm
      intervals. RESULTS: In normal rats, [99mTc]MIBI accumulated throughout the left
      ventricles, and a polar map of ventricular perfusion showed the lowest and
      highest uptakes in the inferior (68 % +/- 4 %) and anterior (92 % +/- 5 %) walls,
      respectively. In the rat MI model, the percentage of polar map with reduced
      [99mTc]MIBI uptake correlated strongly with the percentage of left ventricle with
      MI on autoradiography (r2 = 0.90). CONCLUSIONS: QPS can quantitatively evaluate
      MI severity on myocardial perfusion images in rats, with comparable results to
      autoradiography. This widely available software could promote the development of
      new techniques for analysing cardiac images in small animals.

PMID- 29340891
TI  - Mitomycin C 0.02 and 0.002% efficacy in preventing haze after photorefractive
      keratectomy.
AB  - PURPOSE: To compare MMC 0.002% efficacy in preventing haze after PRK in relation
      to MMC 0.02%. PATIENTS AND METHODS: We conducted a prospective study with
      patients with myopia or myopic astigmatism undergoing PRK in the same conditions.
      After PRK, MMC was applied for 30 s in a concentration of 0.02% on the right eye
      (group 1) and 0.002% on the left eye (group 2). Age, gender, spherical equivalent
      and haze intensity (1, 3, 6 and 12 months postoperatively) were assessed. Haze
      was quantified at biomicroscopy (0-4 +). P < 0.05 was considered statistical
      significant. RESULTS: We evaluated 130 patients, 77 women and 53 men, with a mean
      age of 30.2 +/- 9 years. The spherical equivalent was - 3.66 D in the group 1 and
      - 3.77 D in the group 2. In the 1st month after PRK, incidence of haze was 13.9%
      eyes in group 1 and 14.6% in group 2. In the 3rd month, incidence of haze was
      50.0% eyes in group 1 and 48.5% in group 2 which presented with 3 +/4 + traces of
      haze. In the 12th month, incidence of haze was 7.7% eyes in group 1 and 5.4% in
      group 2. There was no correlation between haze and age (p = 0.279/0.333), gender
      (p = 0.345/0.367) or spherical equivalent (p = 0.100/0.054) in groups 1 and 2,
      respectively. There was no difference in haze between groups 1 and 2 (p = 0.56).
      CONCLUSION: MMC 0.002% was effective in preventing haze after PRK. As MMC long
      term safety has not been proved, we suggest its use in a lower concentration, in
      order to prevent potential complications.

PMID- 29340890
TI  - Association between average daily television viewing time and the incidence of
      ovarian cancer: findings from the Japan Collaborative Cohort Study.
AB  - PURPOSE: Seventy-five percent of epidemiological studies have reported that
      sedentary behavior is associated with ovarian cancer incidence. Although Japan
      has one of the most sedentary populations, with median sitting times of 7 h/day,
      this association has not been investigated. This study aimed to elucidate the
      association between average daily television (TV) viewing time, which is a major
      sedentary behavior, and the incidence of ovarian cancer in a large-scale
      nationwide cohort study in Japan. METHODS: A total of 34,758 female participants
      aged 40-79 years without a history of cancer at baseline were included in the
      study. The inverse probability weighted competing risk model was used to
      calculate the hazard ratio (HR) and 95% confidence interval (CI) for the
      incidence of ovarian cancer. RESULTS: During a median follow-up of 19.4 years, 59
      participants developed ovarian cancer (ICD-10: C56), 2,706 participants developed
      other types of cancer, and 4,318 participants died. Participants who watched TV
      for >= 5 h/day were more likely to develop ovarian cancer than those who watched
      TV for < 2 h/day (HR 2.15; 95% CI 1.54-2.99). CONCLUSION: Our findings suggest
      that reducing the amount of time spent sedentarily may be beneficial for
      preventing ovarian cancer.

PMID- 29340892
TI  - A summer prematriculation program to help students succeed in medical school.
AB  - Medical schools with a diverse student body face the challenge of ensuring that
      all students succeed academically. Many medical schools have implemented
      prematriculation programs to prepare students from diverse backgrounds; however,
      evidence on their impact is largely lacking. In this study, we analyzed
      participants' demographics as well as the impact of the prematriculation program
      on Year 1 performance. Predictive validity of the program was assessed and
      compared to other traditional predictors, including grade point average (GPA) and
      Medical College Admission Test (MCAT) scores and subscores. Linear mixed effect
      models determined the impact of the prematriculation program, and linear
      regression analysis assessed the predictive value of the overall score in the
      prematriculation program and other traditional predictors. Demographics of
      students participating in the prematriculation program from 2013 to 2015 (n = 75)
      revealed a significantly higher prevalence of academically disadvantaged students
      including older students, students with lower GPA and MCAT scores and students of
      racial and ethnic populations that are underrepresented in medicine, compared to
      non-participants (n = 293). Participants performed significantly better in Year 1
      courses that were covered in the prematriculation program compared to courses
      that were not covered. The overall performance in the prematriculation program
      correlated significantly with Year 1 performance and was found to be a strong
      predictor for Year 1 performance. This study suggests that a prematriculation
      program can help students to succeed in the first year of medical school. The
      results have implications for medical schools seeking to implement or evaluate
      the effectiveness of their prematriculation program.

PMID- 29340894
TI  - Correction to: Burst Out of the Dead Land by the Help of Spirituality: A Case
      Study of Living with Blindness and Cancer.
AB  - In the original version of this article, there is a typo in the family name of
      the author. The co-author family name should be Seyed Bagheri; instead, it has
      been published as Seyed bagheri.

PMID- 29340893
TI  - A Prospective Study of Humoral and Cellular Immune Responses to Hepatitis B
      Vaccination in Habitual Marijuana Smokers.
AB  - Exposure to Delta9-tetrahydrocannabinol (THC) in vitro and in animal models can
      significantly impair the differentiation, activation and function of dendritic
      cells, T cells and B cells. However, studies directly assessing the impact of
      marijuana smoking on human immunity are lacking. A prospective study of immune
      responses to a standard hepatitis B vaccination was therefore carried out in a
      matched cohort of 9 marijuana smokers (MS) and 9 nonsmokers (NS). In addition to
      their regular marijuana use, MS smoked four marijuana cigarettes in a monitored
      setting on the day of each vaccination. Blood samples were collected over time to
      assess the development of hepatitis B-specific immunity. The majority of subjects
      from both the NS (8) and MS (6) groups developed positive hepatitis B surface
      antibody titers (>10 IU/L) and of these 6 NS and 5 MS were classified as high
      antibody (good) responders (>100 IU/L). The development of a good response
      correlated with the presence of hepatitis B-specific T cell proliferation and
      cytokine production, resulting in a clear distinction regarding the immune status
      of good responders versus non-responders. However, even though there were
      slighter more non-responders in the MS cohort, there were no significant
      differences between MS and NS with respect to peripheral blood cell phenotypes or
      vaccination-related changes in hepatitis B responses. While a larger cohort may
      be required to rule out a small suppressive effect, our findings do not suggest
      that habitual marijuana smoking exerts a major impact on the development of
      systemic immunity to hepatitis B vaccination.

PMID- 29340895
TI  - Confirming the Tripartite Structure of the Duke University Religion Index: A
      Methodological Approach.
AB  - The present study provided a methodological critique regarding psychometric
      investigations of the Duke University Religion Index (DUREL) and its variants.
      Nine hundred seventeen (630 females and 287 males) university students (M age =
      19.24) completed the DUREL, the Personal Religious Inventory, and the Daily
      Spiritual Experiences Scale online. Confirmatory factor analyses were performed
      to assess a three-factor (organizational religious activity; non-organizational
      religious activity; and intrinsic religiosity) and a unidimensional model of the
      DUREL. Chi-square difference tests were performed, and Akaike information
      criterion values and Bayesian information criterion values were compared between
      the models, each of which supported the three-factor model for the DUREL over the
      unidimensional model. Convergent validity for the three factors of the DUREL
      emerged through Spearman's rho correlations with measures of personal prayer,
      ritual religious attendance, religious integration, Closeness to the Divine. This
      study concluded that the DUREL is a multidimensional measurement of religion for
      use in English-speaking university students, and it provided a broad
      methodological note regarding future investigations of measures of religion or
      spirituality that possess an existing theoretical model.

PMID- 29340896
TI  - Analysis of fecal microbiota in patients with functional constipation undergoing
      treatment with synbiotics.
AB  - This study was performed to identify changes to microbial composition after
      treatment with synbiotics in patients with functional constipation and to define
      the key microbiota in the pathogenesis of functional constipation. Fecal samples
      from 53 patients diagnosed with chronic functional constipation according to the
      Rome III criteria were analyzed using 16S rRNA sequencing. After treatment with
      synbiotics for 1 month, fecal samples were collected from 36 patients; after a
      total of 3 months, fecal samples were collected from 15 patients. The outcomes
      were compared with the intestinal microbiota profiles of 53 healthy community
      volunteers. The microbiota in the constipation group differed from that in the
      treatment group and healthy group. After synbiotic treatment for 1 and 3 months,
      the abundance of Escherichia/Shigella decreased, whereas that of Prevotella_9 and
      Lactococcus increased. Comparison of the microbiota among the three groups showed
      that Prevotella_9 was the characteristic bacteria that decreased in the
      constipation group and increased in the treatment group. Synbiotic treatment can
      improve the microbiota in patients with constipation. Identification of the key
      bacterial genus is important to reveal the mechanism and provide a reliable
      theoretical basis of synbiotic treatment. It will also promote relevant research
      of microbiota treatment and individualized treatments.

PMID- 29340897
TI  - Invasion and translocation of uropathogenic Escherichia coli isolated from
      urosepsis and patients with community-acquired urinary tract infection.
AB  - Uropathogenic Escherichia coli (UPEC) strains are found in high numbers in the
      gut of patients with urinary tract infections (UTIs). We hypothesised that in
      hospitalised patients, UPEC strains might translocate from the gut to the blood
      stream and that this could be due to the presence of virulence genes (VGs) that
      are not commonly found in UPEC strains that cause UTI only. To test this, E. coli
      strains representing 75 dominant clonal groups of UPEC isolated from the blood of
      hospitalised patients with UTI (urosepsis) (n = 22), hospital-acquired (HA) UTI
      without blood infection (n = 24) and strains isolated from patients with
      community-acquired (CA)-UTIs (n = 29) were tested for their adhesion to, invasion
      and translocation through Caco-2 cells, in addition to the presence of 34 VGs
      associated with UPEC. Although there were no differences in the rate and degree
      of translocation among the groups, urosepsis and HA-UTI strains showed
      significantly higher abilities to adhere (P = 0.0095 and P < 0.0001 respectively)
      and invade Caco-2 cells than CA-UTI isolates (P = 0.0044, P = 0.0048
      respectively). Urosepsis strains also carried significantly more VGs than strains
      isolated from patients with only UTI and/or CA-UTI isolates. In contrast, the
      antigen 43 allele RS218 was found more commonly among CA-UTI strains than in the
      other two groups. These data indicate that UPEC strains, irrespective of their
      source, are capable of translocating through gut epithelium. However, urosepsis
      and HA-UTI strains have a much better ability to interact with gut epithelia and
      have a greater virulence potential than CA-UPEC, which allows them to cause blood
      infection.

PMID- 29340898
TI  - Epidemiological aspects of healthcare-associated infections and microbial
      genomics.
AB  - Hospital-acquired infections (HAIs) are a cause of continuously increasing
      morbidity and mortality. Most of these infections are caused by a limited set of
      bacterial species, which share the capability to efficiently spread from patient
      to patient and to easily acquire antibiotic resistance determinants. This renders
      correct and rapid species identification and antibiotic susceptibility testing
      (AST) important and underscores the relevance of bacterial epidemiological
      typing. The latter is needed for the sensitive detection and exact tracing of
      nosocomial spread of these potentially multidrug-resistant microorganisms (MDRO).
      Many microbial typing technologies have been developed and put to some level of
      executive practice, but it seems that the continued evolution in methodology has
      currently reached an apex: there is likely to be scientific and practical
      consensus on the ultimate typing potential of bacterial whole-genome sequencing
      (WGS). The possibility to perform pan-genomic nucleotide-to-nucleotide
      comparisons between strains belonging to a single species and to detect even
      minute changes in nucleotide order will identify closely related organisms, while
      upon accumulation of such mutations, independent descend can be assumed.
      Calibration of difference levels [i.e. number of single nucleotide polymorphisms
      (SNPs)] into categories of inter-strain relatedness needs to be performed in
      order to generate robust, portable typing schemes. Here, we will briefly discuss
      the state of affairs regarding bacterial epidemiology based upon WGS, its
      relatedness with the nomenclature of former typing approaches and the continuing
      need for a global typing language.

PMID- 29340899
TI  - Assessing sensorimotor excitability after spinal cord injury: a reflex testing
      method based on cycling with afferent stimulation.
AB  - : Several studies have examined spinal reflex modulation during leg cycling in
      healthy and spinal cord injury (SCI) subjects. However, the effect of cutaneous
      plantar afferent input on spinal excitability during leg cycling after SCI has
      not been characterised. The aim of the study was to test the feasibility of using
      controlled leg cycling in combination with plantar cutaneous electrical
      stimulation (ES) cycling to assess lower limb spinal sensorimotor excitability in
      subjects with motor complete or incomplete SCI. Spinal sensorimotor excitability
      was estimated by measuring cutaneomuscular-conditioned soleus H-reflex activity.
      Reflex excitability was tested before and after a 10-min ES cycling session in 13
      non-injured subjects, 6 subjects with motor incomplete SCI (iSCI) who had
      moderately impaired gait function, 4 subjects with motor iSCI who had severely
      impaired gait function, and 5 subjects with motor complete SCI (cSCI). No
      modulation of soleus H-reflex with plantar cutaneous stimuli was observed after
      either iSCI or cSCI when compared to non-injured subjects. However, after ES
      cycling, reflex excitability significantly increased in subjects with iSCI and
      moderately impaired gait function. ES cycling facilitated spinal sensorimotor
      excitability only in subjects with motor iSCI with residual gait function.
      Increased spinal excitability induced with a combination of exercise and afferent
      stimulation could be adopted with diagnostic and prognostic purposes to reveal
      the activity-based neurorehabilitation profile of individual subjects with motor
      iSCI. TRIAL REGISTRATION: ISRCTN 26172500 ; retrospectively registered on 15 July
      2016 Graphical abstract ?.

PMID- 29340900
TI  - Xenin: the oldest after insulin?
AB  - Xenin is a regulatory peptide first isolated from the human gastric mucosa. Using
      an open-access protein database MEDLINE (33 million molecules; 11 billion amino
      acid residues) and our original computer program, we conducted a search for the
      xenin motifs in the primary structure of proteins across almost the entire
      taxonomic range of evolution. Motifs with 40% homology to human xenin are already
      present in prokaryotes. Homology reaches 84-96% in single-cell algae and plants,
      becoming complete since bony fishes. We suppose that this regulatory peptide is
      more ancient and significant than is usually thought.

PMID- 29340901
TI  - Mental health-related quality of life and the timing of motherhood: a 16-year
      longitudinal study of a national cohort of young Australian women.
AB  - PURPOSE: We examine timing of motherhood in a longitudinal cohort of young
      Australian women, and its relationship with mental health-related quality of life
      (SF-36 MHI-5), and with sociodemographic, health behaviour and health-related
      variables. METHODS: We analysed longitudinal self-report data from a nationally
      representative cohort of 10,332 Australian women born 1973-1978, surveyed 6 times
      between 1996 (aged 18-23) and 2012 (aged 34-39). RESULTS: Group-based trajectory
      modelling identified four groups. Normative Mothers (46%, mean age at motherhood
      30.5 years) made the transition to motherhood close to the Australian median age.
      Early Mothers (25%, 25.2 years) and Very Early Mothers (7%, 20.0 years) made this
      transition earlier; Not Mothers (22%) had not given birth. Generalised linear
      mixed models showed that all groups improved mean MHI-5 scores over time.
      Patterns of group differences were complex: Normative and Early Mothers scored
      consistently highest; Very Early Mothers scored lowest at most surveys; Not
      Mothers' scores increased relative to others over time. Most effects disappeared
      after adjustment for confounders. Early and Very Early Mothers showed multiple
      indicators of social disadvantage, while Not Mothers had very low rates of
      marriage. CONCLUSIONS: Timing of motherhood is embedded in sociodemographic and
      personal contexts. Women with socioeconomic advantages were characterised by
      higher mental health-related quality of life and later transition to motherhood,
      but adjustment for relative advantage attenuated differences in mental health
      related quality of life. The overall findings suggest a pattern of positive
      adaptation to circumstances, with mental health-related quality of life improving
      through early adulthood regardless of timing of motherhood.

PMID- 29340902
TI  - Validation Study of the Abbreviated Version of the Lubben Social Network Scale
      Spanish Translation among Mexican and Mexican-American Older Adults.
AB  - PURPOSE: To perform a face validity study of the Spanish version of the Lubben
      Social Network Scale (LSNS-6) among Mexican and Mexican-American older adults.
      DESIGN AND METHODS: A cross-national qualitative descriptive approach, based on
      cognitive survey testing and cross-cultural equivalence analysis, was followed to
      assess the face validity of the Spanish version of the LSNS-6. Data were
      collected through 2 focus groups in Los Angeles (LA) and 4 in Mexico City (CDMX).
      Focus groups followed a semi-structured guide. Eligibility criteria included
      being 60 years and older, native Spanish speaking, and not suffering from
      significant cognitive impairments. Four initial focus groups were targeted at
      conducting a face validity assessment of the initial scale, which led to some
      modifications. The two remaining focus groups reassessed the face validity of the
      modified version of the Spanish LSNS-6. RESULTS: 56 older adults participated in
      the focus groups yielding 152 pages of verbatim transcripts. Analysis of the
      transcripts identified relevant themes affecting how Mexican and Mexican American
      older adults understood the items from the LSNS-6 Spanish version, among them:
      labelling of family members and friends, notions of neighborhood, identifying and
      counting people, and understanding of "private matters". This led to propose a
      modified Spanish version of the LSNS-6 following a name generating approach, as
      well as some language and instruction modifications. The face validity of the
      modified version suggested a better understanding. IMPLICATIONS: The study
      proposes that the LSNS-6 Spanish version needs to be adapted for its use among
      Mexican and Mexican American older adults, and we suggest a modified version.
      This potentially implies that social isolation may be more accurately measured in
      a vulnerable group of older adults. Further research is needed to ascertain the
      construct validity and psychometric properties of the modified version.

PMID- 29340904
TI  - Turkish Women's Knowledge, Attitudes, and Behaviors on Wet-Nursing, Milk Sharing
      and Human Milk Banking.
AB  - Purpose The aim of this study was to determine Turkish women's knowledge,
      attitudes, and behaviors on wet-nursing, milk sharing, and human milk banking in
      a primary care setting located in a semi-rural area. Description Donated human
      milk is a feasible option for feeding infants and children. Currently, there is a
      debate on the topic starts with the preparations to launch a human milk bank in a
      large city in Turkey. Several previous papers reported women's opinions in large
      hospital based studies. Little is known about women's views and practice on
      donated human milk in the rural areas of Turkey. Assessment The study sample was
      recruited among married women aged 15-49 years who had given birth within the
      past 5 years and who were in a family health center for any reason in Honaz,
      Denizli, Turkey. A total of 240 women were included in the study. The data were
      collected by questionnaire created by the researchers and consisting of two
      parts: sociodemographic characteristics, and women's knowledge, attitudes, and
      behaviors on wet-nursing, milk sharing and human milk banking. Results Thirty
      women (12.5%) had had a wet-nurse; 20 women (8.7%) wet-nursed babies before; and
      17 (7.2%) of the women's children had a wet-nurse. If necessary, 80.9 and 78.3%
      were willing to accept to do wet-nursing and milk sharing, respectively. 150
      (62.5%) heard of human milk banks; 55 (22.9%) approved of the establishment of
      milk banks. However, only 46 women (19.1%) were willing to donate to the bank.
      Possibility of marriages between milk siblings (76.8%) was the main reason for
      not considering the donation. Women's education was another factor affecting
      their opinion on breast milk sharing and donation to human milk banks. Less
      educated women were sympathetic to milk sharing (p = 0.02), however, more
      educated mothers had a propensity to donate to milk banks (p = 0.02). Conclusion
      Wet-nursing decreased over the years in Turkey, but still an ongoing small child
      feeding method. Most of the women tend to become a wet nurse or do milk sharing
      if it is needed, but they are hesitant to donate their milk to human milk banks,
      mostly due to religious concerns.

PMID- 29340903
TI  - Characterization of ent-kaurene synthase and kaurene oxidase involved in
      gibberellin biosynthesis from Scoparia dulcis.
AB  - Gibberellins (GAs) are ubiquitous diterpenoids in higher plants, whereas some
      higher plants produce unique species-specific diterpenoids. In GA biosynthesis,
      ent-kaurene synthase (KS) and ent-kaurene oxidase (KO) are key players which
      catalyze early step(s) of the cyclization and oxidation reactions. We have
      studied the functional characterization of gene products of a KS (SdKS) and two
      KOs (SdKO1 and SdKO2) involved in GA biosynthesis in Scoparia dulcis. Using an in
      vivo heterologous expression system of Escherichia coli, we found that SdKS
      catalyzed a cyclization reaction from ent-CPP to ent-kaurene and that the SdKOs
      oxidized ent-kaurene to ent-kaurenoic acid after modification of the N-terminal
      region for adaptation to the E. coli expression system. The real-time PCR results
      showed that the SdKS, SdKO1 and SdKO2 genes were mainly expressed in the root and
      lateral root systems, which are elongating tissues. Based on these results, we
      suggest that these three genes may be responsible for the metabolism of GAs in S.
      dulcis.

PMID- 29340905
TI  - Expression of VHL tumor suppressor mRNA and miR-92a in papillary thyroid
      carcinoma and their correlation with clinical and pathological parameters.
AB  - A growing body of evidence suggests a role of the von Hippel-Lindau (VHL) tumor
      suppressor gene in the progression of papillary thyroid carcinoma (PTC). Our
      previous study of VHL in PTCs showed that lower VHL expression was associated
      with aggressive tumor features, but we found no evidence for VHL downregulation
      through common genetic or epigenetic modifications. Several studies pointed to a
      role of microRNA-92a (miR-92a) in the regulation of VHL expression in different
      cancers. In the present study, we examined the expression levels of VHL mRNA and
      miR-92a in 42 pairs of PTCs and matched non-tumor thyroid tissues by means of
      quantitative RT-PCR. We explored the correlation between them and their
      association with clinicopathological parameters. The results revealed that both
      VHL and miR-92a were either up- or downregulated in PTCs compared to
      corresponding non-tumor tissues. On univariate analysis, lower VHL levels were
      significantly associated with extrathyroid spread (P = 0.022) and capsular
      invasion (P = 0.032). Multivariate analysis confirmed the association of low VHL
      with extrathyroid spread (OR 0.246, 95% CI 0.069-0.872, P = 0.038). Higher miR
      92a among PTC tissues associated with the presence of nodal metastases
      (univariate analysis: P = 0.012; multivariate: OR 4.703, 95% CI 1.109-19.938, P =
      0.036). A negative correlation between VHL and miR-92a was observed in a subgroup
      of PTCs having vascular invasion (P = 0.033, r = - 0.673). The data here reported
      demonstrate that the expression of both VHL and miR-92a is deregulated in PTC
      tissues and that in some PTCs they may have opposite roles. These roles, as well
      as their diagnostic and/or prognostic utility, remain to be clarified.

PMID- 29340906
TI  - An exploratory study on the intergenerational transmission of obesity and dieting
      proneness.
AB  - PURPOSE: There is a paucity of research exploring individuals' memories of
      parental dieting behavior, engagement in "fat talk", or criticism of weight or
      eating behavior in childhood. This exploratory study utilized a community sample
      to further characterize the retrospective report of parenting dieting behavior.
      METHODS: A total of 507 participants (78.1% females; 20.7% males; and 1.2%
      transgender) were recruited to participate in an online, self-administered
      survey. RESULTS: Forty percent (216) of participants reported maternal dieting in
      their family of origin and 34% (182) reported maternal fat talk, 24% (120)
      reported paternal dieting, and 11% recalled paternal 'fat talk' (58). Subgroup
      analyses suggest that both male and female participants had greater odds of
      remembering maternal rather than paternal weight or shape criticism and
      encouragement to diet (OR = 58.1; and OR = 3.12; p < 0.0001 for male and female
      participants, respectively). Retrospective report of indirect parental behaviors
      (e.g. parental dieting) also appears to be associated with direct parental
      behaviors (e.g. encouraging children to diet). Additionally, participants who
      recalled maternal encouragement to diet reported a significantly higher adult BMI
      (beta = 1.31, SE = 0.32, p < 0.0001). CONCLUSION: Results provide preliminary
      evidence that a sizeable percentage of both adult male and female participants
      recalled that their parents engaged in fat talk and dieting. In addition,
      participants recalled parental criticism of their own weight or eating behaviors,
      which was associated with recall of parental dieting and fat talk. LEVEL OF
      EVIDENCE: Level V, Descriptive Study.

PMID- 29340907
TI  - Harnessing a Different Dependency: How to Identify and Target Androgen Receptor
      Positive Versus Quadruple-Negative Breast Cancer.
AB  - The androgen receptor (AR) is a promising therapeutic target for a subset of
      triple-negative breast cancers (TNBCs) in which AR is expressed. However, the
      mechanistic action of AR and the degree to which primary and metastatic tumors
      depend on AR, both before and after conventional treatment, remain to be defined.
      We discuss preclinical and clinical data for AR+ TNBC, the difficulties in
      monitoring AR protein levels, new methods for determining AR status, the
      influence of AR on "stemness" in the context of TNBC, the role of combined
      inhibition of sex steroid production and AR, and the role of AR in regulation of
      the immune system. Although the exact role of AR in subsets of TNBC is still
      being characterized, new therapies that target AR and the production of androgens
      may provide additional options for patients with TNBC for whom chemotherapy is
      currently the sole treatment option.

PMID- 29340908
TI  - Fasting Blood Glucose Level in Locally Advanced Non-Small Cell Lung Cancer: a New
      Prognostic Factor?
AB  - Hyperglycemia may lead to proliferation, invasion, apoptosis inhibition,
      migration, and eventually metastasis of cancer cells by several mechanisms. In
      this study, the effect of hyperglycemia on overall survival (OS), disease-free
      survival (DFS), and locoregional recurrence (LRR) was investigated in NSCLC. One
      stage IIIA-IIIB NSCLC patient treated with chemoradiotherapy between 2010 and
      2015 was enrolled. Fasting blood glucose (FBG) levels were recorded in pre
      treatment, treatment, and post-treatment periods. Median age was 54 years (51
      62). Fifty-two patients had squamous cell carcinoma (SCC); 19 had adenocarcinoma.
      Median follow-up was 19 (11-30), median survival was 19 (13-24), and DFS was 9 (7
      11) months. Diabetic patients had shorter survival than non-diabetics 12 (95%CI,
      10-14) vs. 25 months (95%CI,18-32), p = 0.005. Number of patients with LRR was
      also higher in diabetics compared to non-diabetics (8/12 vs. 11/37, p = 0.039).
      OS was shorter in patients with hyperglycemic-FBG and diabetic-FBG levels in pre
      treatment period (log-rank p = 0.03 and 0.023, respectively). Diabetic-FBG level
      in pre-treatment period was found to be the only independent risk factor for
      survival. In subgroup analysis, these differences were apparent in SCC (log-rank
      p = 0.009 for hyperglicemic, log-rank p = 0.017 for diabetic-FBG). LRR was 68% in
      patients with diabetic-FBG, 36.5% in patients with non-diabetic-FBG in post
      treatment period (p = 0.015). Patients with LRR had significantly higher median
      FBG value in post-treatment period compared to non-relapsing patients, 138 mg/dL
      (119-228) and 111 mg/dL (99-164), respectively (p = 0.022). The patients with
      hyperglycemic and diabetic-FBG levels in pre-treatment period had shorter
      survival compared to normoglycemic ones. The patients with diabetic-FBG level in
      post-treatment period had higher LRR, and relapsing patients had higher FBG
      levels in post-treatment period.

PMID- 29340909
TI  - Liposomal Amphotericin B as Monotherapy in Relapsed Coccidioidal Meningitis.
AB  - Coccidioidal meningitis remains a difficult clinical problem, and despite life
      long therapy with triazole antifungals, relapses of disease and medication
      intolerance occur necessitating salvage treatment. We report two patients with
      recurrent coccidioidal meningitis who improved following a 2-week course of
      liposomal amphotericin B monotherapy and discuss potential advantages of this
      treatment option.

PMID- 29340910
TI  - Resistance Mechanism in a Terbinafine-Resistant Strain of Microsporum canis.
AB  - To clarify the terbinafine (TRF) resistance mechanism in a TRF-resistant strain
      of Microsporum canis, the expression of the pleiotropic drug resistance (PDR1),
      multidrug resistance (MDR1), MDR2 and MDR4 genes were investigated by real-time
      quantitative PCR (RT-qPCR) analysis, given the known interaction of the
      corresponding proteins with antifungals and with the efflux blocker FK506. The
      expression of the PDR1, MDR1, MDR2 and MDR4 genes was 2-4 times higher in the TRF
      resistant strain grown in the presence of 0.14 ug/mL of TRF than in TRF
      susceptible strains cultured in the absence of TRF. The TRF-resistant strain
      exhibited MICs of > 32 ug/mL for TRF alone; this resistance was attenuated to an
      MIC of 8 ug/mL in the presence of FK506, indicating that the TRF inhibitory
      concentration index value was < 0.75. The additive effect of the efflux blocker
      FK506 on TRF resistance was detected in the TRF-resistant strain. These results
      indicated that the TRF resistance in this strain reflects overexpression of genes
      encoding ABC transporter proteins.

PMID- 29340911
TI  - Prevalence of Sexual Violence and its Association with Depression among Male and
      Female Patients with Risky Drug Use in Urban Federally Qualified Health Centers.
AB  - Sexual violence (SV) is common; however, the prevalence of SV and its long term
      sequela vary geographically and among subpopulations within the USA. As such, the
      aims of this study are the following: (1) to determine the prevalence of SV, (2)
      to identify correlates of SV, and (3) to determine if SV is associated with
      depression among male and female risky drug users in urban Federally Qualified
      Health Centers (FQHCs) in Los Angeles. This study includes adult patients of five
      urban FQHCs who self-reported risky drug use. We identified survivors of SV and
      those experiencing depression through survey questions that queried, before or
      after age 18, "Were you ever sexually assaulted, molested or raped?" and with the
      RAND Mental Health Index (MHI-5). We utilized Pearson's chi-square tests to
      assess predictors of SV and logistic regression to assess for an association
      between SV and depression. Data collection took place from February 2011 to
      November 2012. Of the 334 study patients, 49% of females and 25% of males
      reported surviving SV. Exposure to SV, (both before 18 years of age and after 18
      years of age) was the strongest predictor of depression among men and women in
      this study (OR 4.7, p < 0.05). These data demonstrate that sexual violence is
      prevalent in this urban FQHC population and is strongly associated with
      depression. Providers should consider screening both men and women with risky
      drug use for SV while health systems should continue to align mental health and
      primary care services to appropriately care for these extremely vulnerable
      patients. Trial Registration Clinical Trials. gov ID NCT01942876, Protocol ID
      DESPR DA022445, http://www.clinicaltrials.gov.

PMID- 29340912
TI  - Predictors of hypoglycemia in hospitalized patients with diabetes mellitus.
AB  - Hypoglycemia is common among hospitalized patients with diabetes mellitus (DM),
      and is associated with increased morbidity and mortality. Identify pre-admission
      risk factors associated with in-hospital hypoglycemia. Historical prospectively
      collected data of adult DM patients hospitalized to medical wards between 2011
      and 2013. Hypoglycemia and serious hypoglycemia were defined as at least one
      blood glucose measurement <= 70 and < 54 mg/dl, respectively, during
      hospitalization. The primary outcome was in-hospital hypoglycemia. The cohort
      included 5301 patients (mean age 73 +/- 13 years, 51% male), including 792
      patients (15%) with hypoglycemia, among them 392 patients (7%) with serious
      hypoglycemia. Patients with hypoglycemia or serious hypoglycemia during
      hospitalization were older, compared to patients without hypoglycemia and more
      likely to have chronic renal failure and cerebrovascular disease. Malignancy and
      female gender were risk factors for hypoglycemia, but not for serious
      hypoglycemia, while congestive heart failure was associated with increased risk
      only for serious hypoglycemia. Diabetes mellitus' duration over 10 years was
      associated with an almost threefold increased risk for hypoglycemia, compared to
      DM duration less than a year. Insulin treatment and glycated hemoglobin > 9% were
      also more common in patients with hypoglycemia. Insulin treatment was associated
      with a fourfold increase in the risk for hypoglycemia among all glycated
      hemoglobin categories. Our results identified several risk factors for in
      hospital hypoglycemia in patients with DM. These findings may lead to appropriate
      monitoring and early intervention to prevent hypoglycemia and to reduce morbidity
      and mortality associated with in-hospital hypoglycemia.

PMID- 29340913
TI  - A Randomized Pilot Trial of a Novel Behavioral Intervention for Chronic Pain
      Tailored to Individuals with HIV.
AB  - Chronic pain is an important and understudied comorbidity in people living with
      HIV (PLWH). We conducted a pilot trial of Skills TO Manage Pain (STOMP), an
      innovative social cognitive theory-based pain self-management intervention
      tailored to PLWH, to assess feasibility, acceptability, and preliminary efficacy.
      Eligibility criteria included being HIV+, >= moderate pain for >= 3 months and a
      score of >= 4 on the three-item PEG pain severity and interference scale.
      Participants were randomized in a 1:1 fashion to STOMP or a usual care
      comparison. Among 22 participants randomized to STOMP, median session attendance
      was 9/12 (75%). Of 19 STOMP participants surveyed, 13 reported being "much
      better" overall since beginning treatment. Brief pain inventory-total scores
      decreased by 2 points in the intervention group and 0.9 in the control group (p =
      0.11). STOMP is feasible, acceptable, and shows preliminary evidence of efficacy
      and promise for a full-scale trial.

PMID- 29340915
TI  - Primed and unprimed rebounding illusory apparent motion.
AB  - Although sequences of uncorrelated random dots can yield a wide range of
      illusorily coherent motion percepts (including translation, rotation,
      contraction, expansion, shear, and rebounding motion), past priming studies have
      relied on two-alternative forced choice tasks that only measure unidirectional
      (positive or negative) priming effects. In Experiment 1 we showed that when
      participants are primed with unidirectional motion and given an additional option
      to report bidirectional (rebounding) motion, they do so frequently, suggesting
      that unidirectional motion can "default" to a rebounding percept. Furthermore,
      rebounding percepts are more prevalent during trials with long frame durations,
      suggesting a role for attention in forming and maintaining these illusory
      percepts. In Experiment 2 we compared rebounding percepts that followed
      unidirectional, drifting primes with rebounding percepts that followed
      bidirectional, rebounding primes, and found that these two types of illusory
      rebounding motion percepts differ systematically in their temporal structures. We
      argue that rebounding percepts following drifting primes can be understood as a
      breakdown of positive priming into an underlying oscillatory state, whereas
      rebounding percepts following rebounding primes may be understood either as (1)
      the initialization of the same oscillatory process, or (2) the entrainment of a
      two-step motion pattern by a higher-order mechanism.

PMID- 29340914
TI  - Structural Effects on HIV Risk Among Youth: A Multi-level Analysis.
AB  - We proposed a multilevel model of structural influences on HIV-risky sexual
      partnerships in a diverse sample of 1793 youth residing in 23 states and the
      District of Columbia. We examined the influence of concentrated disadvantage, HIV
      stigma, and sexual and gender minority stigma on engagement in HIV risky sexual
      partnerships and whether youth's participation in opportunity structures,
      anticipation of HIV stigma, and perceptions of their community as youth
      supportive settings mediated structural effects. After controlling for age, HIV
      status, and race, we found structural HIV stigma had deleterious indirect effects
      on youth's participation in HIV-risky sexual partnerships. Concentrated
      disadvantage and structural sexual and gender minority stigma had direct negative
      effects on youth's perceptions of their communities as supportive and on their
      participation in prosocial activity. Support perceptions had direct, protective
      effects on avoidance of HIV-risky sexual partnerships. Structural stigma
      undermines youth's belief that their communities invest in their safety and well
      being.

PMID- 29340916
TI  - Trapped in a tight spot: Scaling effects occur when, according to the action
      specific account, they should not, and fail to occur when they should.
AB  - The action-specific account of perception claims that what we see is perceptually
      scaled according to our action capacity. However, it has been argued that this
      account relies on an overly confirmatory research strategy-predicting the
      presence of, and then finding, an effect (Firestone & Scholl, 2014). A
      comprehensive approach should also test disconfirmatory predictions, in which no
      effect is expected. In two experiments, we tested one such prediction based on
      the action-specific account, namely that scaling effects should occur only when
      participants intend to act (Witt, Proffitt, & Epstein, 2005). All participants
      wore asymmetric gloves in which one glove was padded with extra material, so that
      one hand was wider than the other. Participants visually estimated the width of
      apertures. The action-specific account predicts that the apertures should be
      estimated as being narrower for the wider hand, but only when participants intend
      to act. We found this scaling effect when it should not have occurred (Exp. 1,
      for participants who did not intend to act), as well as no effect when it should
      have occurred (Exp. 2, for participants who intended to act but were given a
      cover story for the visibility and position of their hands). Thus, the cover
      story used in Experiment 2 eliminated the scaling effect found in Experiment 1.
      We suggest that the scaling effect observed in Experiment 1 likely resulted from
      demand characteristics associated with using a salient, unexplained manipulation
      (e.g., telling people which hand to use to do the task). Our results suggest that
      the action-specific account lacks predictive power.

PMID- 29340917
TI  - Biliary Bypass with Laparoscopic Choledochoduodenostomy.
AB  - Laparoscopic choledochoduodenostomy (LCDD) is employed to treat many benign
      biliary diseases when endoscopic or percutaneous techniques are not feasible. We
      describe our technique for LCDD, which utilizes common bile duct transection and
      an end-to-side biliary-enteric anastomosis. This procedure includes the following
      elements: isolation and transection of the common bile duct, mobilization of the
      duodenum (Kocher maneuver), inspection of the common bile duct, and end-to-side
      biliary-enteric anastomosis. Key details and pitfalls are discussed. Over a 5
      year period, LCDD was performed on 18 patients. Indications included intractable
      abdominal pain (10) and choledocholithiasis (8). The majority of patients, 83%,
      tolerated the operation well with no complications. There was one postoperative
      intra-abdominal abscess and two anastomotic strictures, one in the immediate
      postoperative period and the other 9 months after the operation. The median
      length of stay was 4 days (IQR 3.0-5.3), and there was minimal blood loss. Based
      on our experience, LCDD with transection and end-to-side biliary-enteric
      anastomosis is a safe and effective biliary bypass technique.

PMID- 29340919
TI  - No-Touch Concept Is Invalid for Left-Dominant Perihilar Cholangiocarcinoma.

PMID- 29340918
TI  - Validation of AAST EGS Grade for Acute Pancreatitis.
AB  - BACKGROUND: The AAST recently developed an emergency general surgery (EGS)
      disease grading system to measure anatomic severity. We aimed to validate this
      grading system for acute pancreatitis and compare cross sectional imaging-based
      AAST EGS grade and compare with several clinical prediction models. We
      hypothesize that increased AAST EGS grade would be associated with important
      physiological and clinical outcomes and is comparable to other severity grading
      methods. METHODS: Single institution retrospective review of adult patients
      admitted with acute pancreatitis during 10/2014-1/2016 was performed. Patients
      without imaging were excluded. Imaging, operative, and pathological AAST grades
      were assigned by two reviewers. Summary and univariate analyses were performed.
      AUROC analysis was performed comparing AAST EGS grade with other severity scoring
      systems. RESULTS: There were 297 patients with a mean (+/-SD) age of 55 +/- 17
      years; 60% were male. Gallstone pancreatitis was the most common etiology (28%).
      The overall complication, mortality, and ICU admission rates were 51, 1.3, and
      25%, respectively. The AAST EGS imaging grade was comparable to other severity
      scoring systems that required multifactorial data for readmission, mortality, and
      length of stay. CONCLUSIONS: The AAST EGS grade for acute pancreatitis
      demonstrates initial validity; patients with increasing AAST EGS grade
      demonstrated longer hospital and ICU stays, and increased rates of readmission.
      AAST EGS grades assigned using cross sectional imaging findings were comparable
      to other severity scoring systems. Further studies should determine the
      generalizability of the AAST system. LEVEL OF EVIDENCE: IV Study Type: Single
      institutional retrospective review.

PMID- 29340920
TI  - Pure Laparoscopic Transhepatic Enucleation of a Mucinous Cystic Neoplasm Abutting
      the Major Hepatic Veins at the Hepatocaval Confluence (with Video).
AB  - BACKGROUND: A mucinous cystic neoplasm (MCN) of the liver is a rare disease
      entity, occurring predominantly in the left hemiliver as reported by Simo et al.1
      Thomas et al.2 and Vogt et al.3 Surgical resection of tumors at the hepatocaval
      confluence is a technically demanding procedure. Enucleation procedures have been
      performed for the management of benign or premalignant lesions such as cystic
      tumors as previously described by Thomas et al.2 and Vogt et al.3. We present a
      patient who underwent pure laparoscopic transhepatic enucleation to treat a MCN
      abutting the major hepatic veins at the hepatocaval confluence. METHODS: We
      treated a 77-year-old man who presented with a 5-cm-sized cystic mass at the
      hepatocaval confluence. Using the Pringle maneuver, we performed liver
      parenchymal transection along the junction between the origin of the middle
      hepatic vein (MHV) and the inferior vena cava (IVC) as reported by Kim4. The MHV
      formed the left-sided boundary of the cystic mass. After dissection of the left
      boundary of the cystic wall, the dorsal side of the cystic mass was carefully
      dissected. Liver parenchymal transection was continued up to the right hepatic
      vein (RHV). Laparoscopic enucleation was performed to expose the RHV and MHV, as
      well as the IVC. RESULTS: The operation time was 270 min, the estimated blood
      loss was 80 mL, and no transfusion was necessary in this patient. The final
      histopathological diagnosis of the mass was MCN. Postoperatively, the patient
      recovered uneventfully, and he was discharged on postoperative day 5.
      CONCLUSIONS: Laparoscopic transhepatic enucleation for MCNs at the hepatocaval
      confluence is technically feasible and offers the benefits of a parenchyma
      sparing resection. However, this procedure requires a high level of technical
      skills and shows a steep learning curve.

PMID- 29340921
TI  - Hepatic Paragonimiasis Mimicking Hepatocellular Carcinoma.
AB  - Paragonimiasis is a parasitic lung infection caused by lung flukes of the genus
      Paragonimus. Ectopic infection may occur but rarely involves the liver. Here, we
      report a case of hepatic paragonimiasis in a Chinese man who was initially
      suspected to have hepatocellular carcinoma. He had been previously diagnosed with
      chronic hepatitis B. No specific symptoms or abnormal blood test results were
      observed, except for a significant rise in serum alfa-fetoprotein. Magnetic
      resonance imaging revealed a 12-cm mass with inhomogeneous signal intensity at
      the left lobe of the liver. Laparoscopic left hemihepatectomy was performed. He
      was finally diagnosed as hepatic paragonimiasis upon pathological examination and
      antibody serology. The postoperative course was uneventful. He received a
      standard course of praziquantel and recovered well. Our case is unique in its
      tumor-like characteristic and protrudes the difficulty of differential diagnosis
      with both benignant and malignant hepatic diseases by imaging studies or non
      specific symptoms. Hepatic paragonimiasis is unusual; however, it should be
      considered in the differential diagnosis of liver malignancy by clinicians.

PMID- 29340922
TI  - Prevention of Internal Hernia During Robotic Total Gastrectomy for Gastric
      Cancer.
AB  - BACKGROUND: Postoperative internal hernia (IH) is a potentially life-threatening
      acute protrusion of viscus through an iatrogenic mesenteric defect. In our
      retrospective study of 1943 consecutive gastric cancer (GC) patients who had
      undergone surgery, the incidence of IH after laparoscopic total gastrectomy (LTG)
      was 4.9%.1 This high incidence seems to be caused by decreased adhesion formation
      after LTG. There is no consensus regarding orifice management during robotic
      total gastrectomy (RTG). We therefore developed a new procedure for IH prevention
      during RTG. METHODS: We performed RTG with antecolic Roux-en-Y reconstruction
      using the da Vinci S system (Intuitive, Sunnyvale, CA). We chose an
      intracorporeal side-to-side esophagojejunostomy (overlap method).2 First,
      mesenteric defect of jejunojejunostomy was closed under direct vision following
      retrieval of the stomach. Second, the esophagus hiatus and Petersen's defect were
      closed under laparoscopic vision using robotic suture.3 Finally, the duodenal
      stump and the Roux limb were fixed to prevent torsion of the Roux limb. RESULTS:
      We performed this procedure on five patients between May and October 2017. The
      median duration of surgery was 395 min (range, 319-442 min), median bleeding was
      60 ml (range, 35-140 ml). There were no anastomosis-related complications higher
      than Clavien-Dindo grade II in any patients.4 Although the follow-up period is
      less than 1 year, no IH after RTG has been observed in any patients. CONCLUSION:
      Regarding short-term surgical outcomes, this procedure is recommended for GC
      patients who undergo RTG. However, more long-term follow-up for patients who have
      undergone RTG with closure of all mesenteric defects is required.

PMID- 29340923
TI  - CT Features of Calcifying Fibrous Tumor of the Stomach.

PMID- 29340924
TI  - Impact of Preoperative Opioid Use After Emergency General Surgery.
AB  - BACKGROUND: Preoperative exposure to narcotics has recently been associated with
      poor outcomes after elective major surgery, but little is known as to how
      preoperative opioid use impacts outcomes after common, emergency general surgical
      procedures (EGS). METHODS: A high-volume, single-center analysis was performed on
      patients who underwent EGS from 2012 to 2013. EGS was defined as the seven
      emergent operations that account for 80% of the national burden. Preoperative
      opioid use was defined as having an active opioid prescription within 7 days
      prior to surgery. Chronic opioid use was defined as having an opioid prescription
      concurrent with 90 days after discharge. RESULTS: A total of 377 patients
      underwent EGS during the study period. Preoperative opioid use was present in 84
      patients (22.3%). Preoperative opioid users had longer hospital LOS (10.5 vs 6
      days), higher costs of care ($25,331 vs $11,454), and higher 30-day readmission
      rates (22.6 vs 8.2%) compared with opioid-naive patients (p < 0.001 each). After
      covariate adjustment, preoperative opioid use was predictive of LOS (RR 1.19
      [1.01-1.41]) and 30-day hospital readmission (OR 2.69 [1.25-5.75]) (p < 0.05
      each). Total direct cost was not different after modeling. Preoperative opioid
      users required more narcotic refills compared with opioid-naive patients (5 vs 0
      refills, p < 0.001). After discharge, 15.4% of opioid-naive patients met criteria
      for chronic opioid use, vs 77.4% in preoperative opioid users (p < 0.001).
      CONCLUSIONS: Preoperative opioid use is associated with greater resource
      utilization after emergency general surgery, as well as vastly different
      postoperative opioid prescription patterns. These findings may help to inform the
      impact of preoperative opioid use on patient care, and its implications on
      hospital and societal cost.

PMID- 29340925
TI  - Response to Letter to the Editor on "Utility of Endoanal Ultrasonography in
      Assessment of Primary and Recurrent Anal Fistulas and for Detection of Associated
      Anal Sphincter Defects".

PMID- 29340926
TI  - Gastrointestinal histoplasmosis ileal stricture successfully treated with through
      the-scope balloon dilation in a patient with hyperimmunoglobulin M syndrome.
AB  - Gastrointestinal histoplasmosis is common in patients with disseminated disease
      affecting both immunocompetent and immunocompromised patients. However, it is
      often unrecognized due to a lack of specific signs and symptoms. It has only
      rarely been reported to cause small bowel obstruction, during which surgical
      treatment was nearly always necessary. Little is known about the usefulness of
      endoscopic therapy in gastrointestinal histoplasmosis associated strictures. We
      report the case of a 32-year-old man with a history of hyperimmunoglobulin M
      syndrome who presented with small bowel obstruction secondary to disseminated
      gastrointestinal histoplasmosis. Treatment was successful with a through-the
      scope balloon dilator in combination with medical therapy. This report adds to
      the limited data available on the benefit of endoscopic therapy in infectious
      strictures, particularly gastrointestinal histoplasmosis.

PMID- 29340927
TI  - Achalasia Cardia in a Young Infant.
AB  - Achalasia cardia is an esophageal motility disorder rarely reported in children
      and more so in young infants. Common clinical presentations include vomiting,
      dysphagia, regurgitation, recurrent pulmonary aspiration and failure to thrive.
      Diagnosis is made by barium swallow study and esophageal manometry, which is the
      gold standard test. Pharmocological management and endotherapy often fails and
      results in recurrence of symptoms. Laparoscopic Hellers myotomy, with or without
      anti-reflux procedure is the standard treatment of choice for children. Per-oral
      endoscopic myotomy is utilized for treatment of achalasia in adults, but its
      safety, efficacy, and feasibility is not studied in children.

PMID- 29340930
TI  - The Microbiome and Neurologic Disease: Past and Future of a 2-Way Interaction.

PMID- 29340928
TI  - Microbiota Signaling Pathways that Influence Neurologic Disease.
AB  - Though seemingly distinct and autonomous, emerging evidence suggests there is a
      bidirectional interaction between the intestinal microbiota and the brain. This
      crosstalk may play a substantial role in neurologic diseases, including anxiety,
      depression, autism, multiple sclerosis, Parkinson's disease, and, potentially,
      Alzheimer's disease. Long hypothesized by Metchnikoff and others well over 100
      years ago, investigations into the mind-microbe axis is now seeing a rapid
      resurgence of research. If specific pathways and mechanisms of interaction are
      understood, it could have broad therapeutic potential, as the microbiome is
      environmentally acquired and can be modified to promote health. This review will
      discuss immune, endocrine, and neural system pathways that interconnect the gut
      microbiota to central nervous system and discuss how these findings might be
      applied to neurologic disease.

PMID- 29340931
TI  - VascuTrainer: A Mobile and Disposable Bioreactor System for the Conditioning of
      Tissue-Engineered Vascular Grafts.
AB  - In vitro tissue engineering of vascular grafts requires dynamic conditioning in a
      bioreactor system for in vitro tissue maturation and remodeling to receive a
      mechanically adequate and hemocompatible implant. The goal of the current work
      was to develop a bioreactor system for the conditioning of vascular grafts which
      is (i) able to create a wide range of flow, pressure and frequency conditions,
      including physiological ones; (ii) compact and easy to assemble; (iii)
      transportable; (iv) disposable. The system is driven by a small centrifugal pump
      controlled via a custom-made control unit, which can also be operated on
      batteries to allow for autonomous transportation. To show the potential of the
      newly developed bioreactor system small-caliber vascular composite grafts (n = 5,
      internal diameter = 3 mm, length = 12.5 cm) were fabricated using a fibrin
      scaffold embedding human umbilical artery smooth muscle cells and a
      polyvinylidene fluoride warp-knitted macroporous mesh. Subsequently, the vascular
      grafts were endothelialized and mounted in the bioreactor system for
      conditioning. The conditioning parameters remained within the predefined range
      over the complete conditioning period and during operation on batteries as tested
      for up to 25 h. Fabrication and pre-conditioning under arterial pressure and
      shear stress conditions resulted in robust and hemocompatible tissue-engineered
      vascular grafts. Analysis of immunohistochemical stainings against extracellular
      matrix and cell-specific proteins revealed collagen I and collagen III
      deposition. The luminal surface was confluently covered with endothelial cells.
      The developed bioreactor system showed cytocompatibility and pH, pO2, pCO2,
      glucose and lactate stayed constant. Sterility was maintained during the complete
      fabrication process of the vascular grafts. The potential of a versatile and
      mobile system and its functionality by conditioning tissue-engineered vascular
      grafts under physiological pressure and flow conditions could be demonstrated.

PMID- 29340932
TI  - Robotic Scanning Device for Intraoperative Thyroid Gland Endomicroscopy.
AB  - Probe-based confocal laser endomicroscopy has a high potential to be a promising
      tool that can provide intraoperative high-resolution in vivo morphological
      imaging at cellular and subcellular levels for thyroidectomy, and allow real-time
      assessment of tumor margins. However, the typical images acquired with this
      technique cover a very small area limited by the field of view of the probe,
      accompanied by tissue deformation and inconsistent probe-tissue contact when
      operated manually. In this paper, a novel compact robotic device for large area
      scanning has been developed. The device can scan a large surface in a spiral
      trajectory by rotating the tip frame along the spiral groove of the base frame.
      The fiber Bragg grating sensor with a passive linear structure is used to detect
      and maintain a stable probe-tissue contact force during scanning. An active
      linear actuation is also integrated for adjusting the probe-tissue contact level
      prior to each scan. Results demonstrate that the scanning device ensures a
      suitable probe-tissue contact force and compensates for simulated hand tremor.
      Mosaicing results of lens tissue paper and porcine belly tissue with both bench
      and hand-held experiments show the effectiveness and usability of the device,
      demonstrating the potential clinical value of the system.

PMID- 29340933
TI  - Forces Generated by Vastus Lateralis and Vastus Medialis Decrease with Increasing
      Stair Descent Speed.
AB  - Stair descent (SD) is a common, difficult task for populations who are elderly or
      have orthopaedic pathologies. Joint torques of young, healthy populations during
      SD increase at the hip and ankle with increasing speed but not at the knee,
      contrasting torque patterns during gait. To better understand the sources of the
      knee torque pattern, we used dynamic simulations to estimate knee muscle forces
      and how they modulate center of mass (COM) acceleration across SD speeds (slow,
      self-selected, and fast) in young, healthy adults. The vastus lateralis and
      vastus medialis forces decreased from slow to self-selected speeds as the
      individual lowered to the next step. Since the vasti are primary contributors to
      vertical support during SD, they produced lower forces at faster speeds due to
      the lower need for vertical COM support observed at faster speeds. In contrast,
      the semimembranosus and rectus femoris forces increased across successive speeds,
      allowing the semimembranosus to increase acceleration downward and forward and
      the rectus femoris to provide more vertical support and resistance to forward
      progression as SD speed increased. These results demonstrate the utility of
      dynamic simulations to extend beyond traditional inverse dynamics analyses to
      gain further insight into muscle mechanisms during tasks like SD.

PMID- 29340929
TI  - S-Adenosyl Methionine and Transmethylation Pathways in Neuropsychiatric Diseases
      Throughout Life.
AB  - S-Adenosyl methionine (SAMe), as a major methyl donor, exerts its influence on
      central nervous system function through cellular transmethylation pathways,
      including the methylation of DNA, histones, protein phosphatase 2A, and several
      catecholamine moieties. Based on available evidence, this review focuses on the
      lifelong range of severe neuropsychiatric and neurodegenerative diseases and
      their associated neuropathologies, which have been linked to the deficiency/load
      of SAMe production or/and the disturbance in transmethylation pathways. Also
      included in this review are the present-day applications of SAMe in the treatment
      in these diseases in each age group.

PMID- 29340934
TI  - Impact Force, Polar Gap and Modal Parameters Predict Acetabular Cup Fixation: A
      Study on a Composite Bone.
AB  - The balanced initial fixation of an implant makes up a crucial condition for its
      long-term survival. However, the quantification of initial fixation is no easy
      task and, to date, only qualitative assessments can be made. Although the concept
      of measuring fixation by means of vibration analysis is already widely used in
      dental implantology, the rigorous application of this method for the assessment
      of the fixation of femoral and acetabular components remains a challenge.
      Moreover, most studies on this subject have tended to focus solely on the femoral
      stem even though acetabular cup fixation is also important and even more
      difficult with respect to qualitative measurement. This study describes a
      comprehensive experiment aimed at assessing acetabular cup fixation. Fixation is
      expressed in terms of the impact force and polar gap variables, which are
      correlated with the modal properties of the acetabular implant during the various
      insertion stages. The predictive capabilities of modal frequencies and frequency
      functions were investigated by means of surrogate models based on the Gaussian
      process and functional principal component analysis. The prediction accuracy of
      the proposed models was in the range 82-94%. The results indicate that natural
      frequencies, reduced frequency, impact force and polar gap features provide great
      potential in terms of the prediction of implant fixation.

PMID- 29340935
TI  - Endoscopic Treatments of GERD.
AB  - OPINION STATEMENT: PURPOSE OF REVIEW: Endoscopic therapies for gastroesophageal
      reflux disease (GERD) are minimally invasive techniques which fill the gap
      between the medical therapy with proton pump inhibitors (PPIs) and surgical
      fundoplication. The main endoscopic therapies currently available in the USA are
      transoral incisionless fundoplication (TIF) using EsophyX device or less
      commonly, Medigus Ultrasonic Surgical Endostapler, and radiofrequency energy
      delivery to lower esophageal sphincter using Stretta device. Our aim was to
      examine the available evidence for these therapies. RECENT FINDINGS: Consistent
      evidence for subjective improvement is available for fundoplication using EsophyX
      and Stretta, but improvement in objective parameters for GERD is not seen or
      evaluated in all the studies. There is a reduction in long-term efficacy seen
      with TIF and also to a lesser extent with Stretta. Endoscopic therapies do not
      replace surgical fundoplication and therefore are useful in patients with
      breakthrough symptoms on PPI such as regurgitation or those reluctant to take
      long-term PPI. An ideal patient is one who has symptoms and objective evidence of
      GERD such as abnormal pH study or erosive esophagitis without any significant
      anatomic distortion such as a hiatal hernia. Since these are endoluminal
      procedures, they do not address the hiatal hernia reduction or repair of crural
      defect. Adequate training in the technique and careful patient selection are
      essential prior to embarking on these procedures.

PMID- 29340936
TI  - Application of Color Transformation Techniques in Pediatric Spinal Cord MR
      Images: Typically Developing and Spinal Cord Injury Population.
AB  - The purpose of this study was to evaluate an improved and reliable visualization
      method for pediatric spinal cord MR images in healthy subjects and patients with
      spinal cord injury (SCI). A total of 15 pediatric volunteers (10 healthy subjects
      and 5 subjects with cervical SCI) with a mean age of 11.41 years (range 8-16
      years) were recruited and scanned using a 3.0T Siemens Verio MR scanner. T2
      weighted axial images were acquired covering entire cervical spinal cord level C1
      to C7. These gray-scale images were then converted to color images by using five
      different techniques including hue-saturation-value (HSV), rainbow, red-green
      blue (RGB), and two enhanced RGB techniques using automated contrast stretching
      and intensity inhomogeneity correction. Performance of these techniques was
      scored visually by two neuroradiologists within three selected cervical spinal
      cord intervertebral disk levels (C2-C3, C4-C5, and C6-C7) and quantified using
      signal to noise ratio (SNR) and contrast to noise ratio (CNR). Qualitative and
      quantitative evaluation of the color images shows consistent improvement across
      all the healthy and SCI subjects over conventional gray-scale T2-weighted
      gradient echo (GRE) images. Inter-observer reliability test showed moderate to
      strong intra-class correlation (ICC) coefficients in the proposed techniques (ICC
      > 0.73). The results suggest that the color images could be used for
      quantification and enhanced visualization of the spinal cord structures in
      addition to the conventional gray-scale images. This would immensely help towards
      improved delineation of the gray/white and CSF structures and further aid towards
      accurate manual or automatic drawings of region of interests (ROIs).

PMID- 29340937
TI  - Association between Electronic Medical Record Implementation of Default Opioid
      Prescription Quantities and Prescribing Behavior in Two Emergency Departments.

PMID- 29340939
TI  - The Influence of Financial Strain on Health Decision-Making.

PMID- 29340938
TI  - Pharmacologic Treatment of Hypertensive Urgency in the Outpatient Setting: A
      Systematic Review.
AB  - BACKGROUND: Hypertensive urgency (HU), defined as acute severe uncontrolled
      hypertension without end-organ damage, is a common condition. Despite its
      association with long-term morbidity and mortality, guidance regarding immediate
      management is sparse. Our objective was to summarize the evidence examining the
      effects of antihypertensive medications to treat. METHODS: We searched the
      PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Database of
      Abstracts of Reviews of Effects (DARE), Cochrane Database of Systematic Reviews,
      Web of Science, Google Scholar, and Embase through May 2016. STUDY SELECTION: We
      evaluated prospective controlled clinical trials, case-control studies, and
      cohort studies of HU in emergency room (ER) or clinic settings. We initially
      identified 11,223 published articles. We reviewed 10,748 titles and abstracts and
      identified 538 eligible articles. We assessed the full text for eligibility and
      included 31 articles written in English that were clinical trials or cohort
      studies and provided blood pressure data within 48 h of treatment. Studies were
      appraised for risk of bias using components recommended by the Cochrane
      Collaboration. The main outcome measured was blood pressure change with
      antihypertensive medications. Since studies were too diverse both clinically and
      methodologically to combine in a meta-analysis, tabular data and a narrative
      synthesis of studies are presented. RESULTS: We identified only 20 double-blind
      randomized controlled trials and 12 cohort studies, with 262 participants in
      prospective controlled trials. However, we could not pool the results of studies.
      In addition, comorbidities and their potential contribution to long-term
      treatment of these subjects were not adequately addressed in any of the reviewed
      studies. CONCLUSIONS: Longitudinal studies are still needed to determine how best
      to lower blood pressure in patients with HU. Longer-term management of
      individuals who have experienced HU continues to be an area requiring further
      study, especially as applicable to care from the generalist.

PMID- 29340940
TI  - Characterizing Potentially Preventable Admissions: A Mixed Methods Study of
      Rates, Associated Factors, Outcomes, and Physician Decision-Making.
AB  - BACKGROUND: Potentially preventable admissions are a target for healthcare cost
      containment. OBJECTIVE: To identify rates of, characterize associations with, and
      explore physician decision-making around potentially preventable admissions.
      DESIGN: A comparative cohort study was used to determine rates of potentially
      preventable admissions and to identify associated factors and patient outcomes. A
      qualitative case study was used to explore physicians' clinical decision-making.
      PARTICIPANTS: Patients admitted from the emergency department (ED) to the general
      medicine (GM) service over a total of 4 weeks were included as cases (N = 401).
      Physicians from both emergency medicine (EM) and GM that were involved in the
      cases were included (N = 82). APPROACH: Physicians categorized admissions as
      potentially preventable. We examined differences in patient characteristics,
      admission characteristics, and patient outcomes between potentially preventable
      and control admissions. Interviews with participating physicians were conducted
      and transcribed. Transcriptions were systematically analyzed for key concepts
      regarding potentially preventable admissions. KEY RESULTS: EM and GM physicians
      categorized 22.2% (90/401) of admissions as potentially preventable. There were
      no significant differences between potentially preventable and control admissions
      in patient or admission characteristics. Potentially preventable admissions had
      shorter length of stay (2.1 vs. 3.6 days, p < 0.001). There was no difference in
      other patient outcomes. Physicians discussed several provider, system, and
      patient factors that affected clinical decision-making around potentially
      preventable admissions, particularly in the "gray zone," including risk of
      deterioration at home, the risk of hospitalization, the cost to the patient, and
      the presence of outpatient resources. Differences in provider training, risk
      assessment, and provider understanding of outpatient access accounted for
      differences in decisions between EM and GM physicians. CONCLUSIONS: Collaboration
      between EM and GM physicians around patients in the gray zone, focusing on
      patient risk, cost, and outpatient resources, may provide an avenues for reducing
      potentially preventable admissions and lowering healthcare spending.

PMID- 29340941
TI  - Internal Medicine Residents' Attitudes Toward Simulated Depressed Cardiac
      Patients During an Objective Structured Clinical Examination: A Randomized Study.
AB  - BACKGROUND: Physician biases toward mental conditions such as depression have
      been shown to adversely affect medical outcomes. OBJECTIVE: To explore the
      relationship between residents' explicit bias toward depressed patients and their
      clinical skills on a cardiac case during an objective structured clinical exam
      (OSCE). DESIGN: Prospective parallel randomized controlled study. PARTICIPANTS:
      One hundred eighty-five internal medicine residents from three residency programs
      in two states. INTERVENTION: During October-November 2015, residents were
      randomized to either a depressed or non-depressed standardized patient (SP)
      presenting with acute chest pain. MAIN MEASURES: The Medical Condition Regard
      Scale (MCRS) assessed residents' explicit bias toward patients with depression.
      Their clinical skills (history-taking, physical examination, patient counseling,
      patient-physician interaction (PPI), differential diagnosis, and workup plan) and
      facial expressions were rated during an OSCE. KEY RESULTS: No significant
      relationships were found between resident explicit bias and clinical skill
      measurements. Residents who examined the depressed SP scored lower, on average,
      on history-taking (t [183] = -2.77, p < 0.01, Cohen's d = 0.41) and higher on PPI
      (t [183] = 2.24, p < 0.05, Cohen's d = 0.33) than residents examining the non
      depressed SP. There were no differences, on average, between stations on physical
      examination, counseling, correct diagnosis, workup plan, or overall SP
      satisfaction. Facial recognition software demonstrated that residents with a non
      depressed SP had more neutral expressions than depressed-SP residents (t [133] = 
      2.46, p < 0.05, Cohen's d = 0.46), and residents with a depressed SP had more
      disgusted expressions than non-depressed-SP residents (t [83.52] = 2.10, p <
      0.05, Cohen's d = 0.28). CONCLUSIONS: Extrinsic bias did not predict OSCE
      performance in this study. Some differences were noted in the OSCE performance
      between the two stations. Further study is needed to examine the effects of
      patient mental health conditions on physician examination procedures, diagnostic
      behaviors, and patient outcomes.

PMID- 29340942
TI  - Gluteal Augmentation-Associated Mycobacterial Infection.

PMID- 29340943
TI  - A prospective investigation of rumination and executive control in predicting
      overgeneral autobiographical memory in adolescence.
AB  - The CaR-FA-X model (Williams et al., 2007), or capture and rumination (CaR),
      functional avoidance (FA), and impaired executive control (X), is a model of
      overgeneral autobiographical memory (OGM). Two mechanisms of the model,
      rumination and executive control, were examined in isolation and in interaction
      in order to investigate OGM over time. Across two time points, six months apart,
      a total of 149 adolescents (13-16 years) completed the minimal-instruction
      autobiographical memory test, a measure of executive control with both emotional
      and nonemotional stimuli, and measures of brooding rumination and reflective
      pondering. The results showed that executive control for emotional information
      was negatively associated with OGM, but only when reflective pondering levels
      were high. Therefore, in the context of higher levels of reflective pondering,
      greater switch costs (i.e., lower executive control) when processing emotional
      information predicted a decrease in OGM over time.

PMID- 29340944
TI  - Persons with disability, social deprivation and an emergency medical admission.
AB  - BACKGROUND: The community level of disability and social deprivation may result
      in an emergency hospitalisation; we have examined the annual admission incidence
      rate for emergency medical conditions in relation to the community prevalence of
      such factors. METHODS: All emergency medical admissions (96,305 episodes in
      50,612 patients) within the institution's catchment area were examined between
      2002 and 2016. The frequency of disability, level of full-time carers and
      unemployment for the 74 electoral divisions of the catchment area was regressed
      against admission rates; incidence rate ratios (IRR) were calculated using
      truncated Poisson regression. RESULTS: Disability was present in 12.1% of the
      catchment area population (95% CI = 9.7-15.0). The annual admission incidence
      rates/1000 population across disability quintiles for the more affluent areas
      increased from Q1 7.6 (95% CI = 7.4-7.8) to Q5 27.3 (95% CI = 27.0-27.5) and for
      the more deprived area from Q1 16.6 (95% CI = 16.4, 16.8) to and Q5 40.4 (95% CI
      = 40.1-40.7). Disability status influenced the overall admission IRR (compared
      with Q1/Q3) for Q4/Q5 1.11 (95% CI = 1.09-1.13) showing an increased rate of
      hospitalisation for the more deprived areas. Community disability levels
      interacted with local area unemployment and frequency of full-time carers; as
      they increased, a linear relationship between disability and the admission rate
      incidence was demonstrated. CONCLUSION: Local catchment area disability
      prevalence rates in addition to social deprivation factors are an important
      determinant of the annual incidence rate of emergency medical admissions.

PMID- 29340945
TI  - Electromagnetic induction sensor for dynamic testing of coagulation process.
AB  - With the increasing demand for coagulation POCT for patients in the surgery
      department or the ICU, rapid coagulation testing techniques and methods have
      drawn widespread attention from scholars and businessmen. This paper proposes the
      use of electromagnetic induction sensor probe for detection of dynamic process
      causing changes in the blood viscosity and density before and after coagulation
      based on the damped vibration principle, in order to evaluate the coagulation
      status. Utilizing the dynamic principle, the differential equation of vibration
      system comprising elastic support and electromagnetic induction device is
      established through sensor dynamic modeling. The structural parameters of elastic
      support are optimized, and the circular sheet spring is designed. Furthermore,
      harmonic response analysis and vibration fatigue coupling analysis are performed
      on the elastic support of the sensor by considering the natural frequency of the
      system, and the electromagnetic induction sensor testing device is set up. Using
      the device and coagulation reagent, the standard curve for coagulation POCT is
      plotted, and the blood sample application in clinical patients is established,
      which are methodologically compared with the imported POCT coagulation analyzer.
      The results show that the sensor designed in this paper has a first-order natural
      frequency of 11.368 Hz, which can withstand 5.295 * 102 million times of
      compressions and rebounds. Its correlation with the results of SONOCLOT analyzer
      reaches 0.996, and the reproducibility 0.002. The electromagnetic induction
      coagulation testing sensor designed has good elasticity and anti-fatigue, which
      can meet the accuracy requirement of clinical detection. This study provides the
      core technology for developing the electromagnetic induction POCT instrument for
      dynamic testing of coagulation process.

PMID- 29340946
TI  - Standardisation of shielding of medical X-ray installations.

PMID- 29340947
TI  - The impact of depuration on mussel hepatopancreas bacteriome composition and
      predicted metagenome.
AB  - Due to the rapid elimination of bacteria through normal behaviour of filter
      feeding and excretion, the decontamination of hazardous contaminating bacteria
      from shellfish is performed by depuration. This process, under conditions that
      maximize shellfish filtering activity, is a useful method to eliminate
      microorganisms from bivalves. The microbiota composition in bivalves reflects
      that of the environment of harvesting waters, so quite different bacteriomes
      would be expected in shellfish collected in different locations. Bacterial
      accumulation within molluscan shellfish occurs primarily in the hepatopancreas.
      In order to assess the effect of the depuration process on these different
      bacteriomes, in this work we used 16S RNA pyrosequencing and metagenome
      prediction to assess the impact of 15 h of depuration on the whole hepatopancreas
      bacteriome of mussels collected in three different locations.

PMID- 29340948
TI  - A Case of Concomitant Pemphigus Foliaceus and Oral Pemphigus Vulgaris.
AB  - Pemphigus is a chronic autoimmune condition that can affect multiple areas of the
      body. The two main subtypes of pemphigus are pemphigus vulgaris (PV) and
      pemphigus foliaceus (PF) which can rarely occur concurrently or even transition
      from one to the other. The process of transition may be explained by qualitative
      changes in desmoglein autoantibody profile. We present a rare case of concomitant
      PF and oral PV and explore the literature on transitions between pemphigus
      subtypes and whether this case could represent a transition from PF to PV.
      Furthermore, the realities of multidisciplinary patient management are discussed.

PMID- 29340949
TI  - Hybrid Central Odontogenic Fibroma/Central Giant Cell Lesion: A Missing Report.

PMID- 29340950
TI  - Dermatologic Lesions Submitted to an Oral and Maxillofacial Pathology Biopsy
      Service: An Analysis of 2487 Cases.
AB  - Skin lesions are often submitted to oral and maxillofacial pathology practices.
      The purpose of this study is to evaluate the frequency, distribution,
      variability, and composition of dermatologic lesions within a large oral and
      maxillofacial pathology biopsy service. An IRB-approved retrospective search of
      skin lesions diagnosed at University of Florida oral and maxillofacial pathology
      biopsy service between 1994 and 2015 was performed. 2487 cases were included in
      the study. Gender was reported in 2466 cases, of which 59% were male and 41%
      female. Age was provided in 2367 cases and ranged from 2 weeks to 96 years with
      an average of 55 years. Location was indicated in 2473 cases. Lips were the most
      common (41.7%), followed by face (25.3%), neck (7.4%), nose (6.5%), periorbital
      (5.3%), ear (4.1%), and scalp (3.8%). Of the 2487 cases, five diagnoses (actinic
      keratosis/cheilitis, intradermal nevus, epidermal inclusion cyst, seborrheic
      keratosis, and basal cell carcinoma) constituted 84.4% of the cases. 69 of 2487
      cases (2.8%) resulted in dermatopathologic consultation prior to final reporting.
      Skin lesions accounted for ~ 1.0% of all lesions submitted to an oral and
      maxillofacial pathology biopsy service. This study found a large variation in the
      dermatologic lesions submitted to an oral pathology biopsy service. Although most
      were routine in complexity, dermatopathology consultation was an important tool
      in the diagnosis of the more challenging cases. This study may help pathologists
      gain a better understanding of the frequency and variability of dermatologic
      lesions submitted to an oral and maxillofacial pathology biopsy service and
      promote more interdisciplinary consultation within the field. This study
      evaluated the incidence and scope of dermatologic lesions submitted to a large
      oral and maxillofacial pathology biopsy service over a long time period. A wide
      scope of lesions was found, and dermatopathology consultation was important to
      quality assurance.

PMID- 29340952
TI  - RFAthM6A: a new tool for predicting m6A sites in Arabidopsis thaliana.
AB  - KEY MESSAGE: We curated a reliable dataset of m6A sites in Arabidopsis thaliana,
      built competitive models for predicting m6A sites, extracted predominant rules
      from the prediction models and analyzed the most important features. In
      biological RNA, approximately 150 chemical modifications have been discovered, of
      which N6-methyladenine (m6A) is the most prevalent and abundant. This
      modification plays an essential role in a myriad of biological mechanisms and
      regulates RNA localization, nuclear export, translation, stability, alternative
      splicing, and other processes. However, m6A-seq and other wet-lab techniques do
      not easily facilitate accurate and complete determination of m6A sites across the
      transcriptome. Therefore, the use of computational methods to establish accurate
      models for predicting m6A sites is essential. In this work, we manually curated a
      reliable dataset of m6A sites and non-m6A sites and developed a new tool called
      RFAthM6A for predicting m6A sites in Arabidopsis thaliana. Briefly, RFAthM6A
      consists of four independent models named RFPSNSP, RFPSDSP, RFKSNPF and RFKNF and
      strict benchmarks show that the AUC values of the four models reached 0.894,
      0.914, 0.920 and 0.926, respectively in a fivefold cross validation and the
      prediction performance of RFPSDSP, RFKSNPF and RFKNF exceeded that of three
      previously reported models (AthMethPre, M6ATH and RAM-NPPS). Linear combination
      of the prediction scores of RFPSDSP, RFKSNPF and RFKNF improved the prediction
      performance. We also extracted several predominant rules that underlie the m6A
      site identification from the trained models. Furthermore, the most important
      features of the predictors for the m6A site identification were also analyzed in
      depth. To facilitate use of our proposed models by interested researchers, all
      the source codes and datasets are publicly deposited at
      https://github.com/nongdaxiaofeng/RFAthM6A .

PMID- 29340951
TI  - A perspective on multi-target drug discovery and design for complex diseases.
AB  - Diseases of infection, of neurodegeneration (such as Alzheimer's and Parkinson's
      diseases), and of malignancy (cancers) have complex and varied causative factors.
      Modern drug discovery has the power to identify potential modulators for multiple
      targets from millions of compounds. Computational approaches allow the
      determination of the association of each compound with its target before chemical
      synthesis and biological testing is done. These approaches depend on the prior
      identification of clinically and biologically validated targets. This Perspective
      will focus on the molecular and computational approaches that underpin drug
      design by medicinal chemists to promote understanding and collaboration with
      clinical scientists.

PMID- 29340953
TI  - MdPIN1b encodes a putative auxin efflux carrier and has different expression
      patterns in BC and M9 apple rootstocks.
AB  - KEY MESSAGE: Lower promoter activity is closely associated with lower MdPIN1b
      expression in the M9 interstem, which might contribute to the dwarfing effect in
      apple trees. Apple trees grafted onto dwarfing rootstock Malling 9 (M9) produce
      dwarfing tree architecture with high yield and widely applying in production.
      Previously, we have reported that in Malus 'Red Fuji' (RF) trees growing on M9
      interstem and Baleng Crab (BC) rootstock, IAA content was relatively higher in
      bark tissue of M9 interstem than that in scion or rootstock. As IAA polar
      transportation largely depends on the PIN-FORMED (PIN) auxin efflux carrier.
      Herein, we identify two putative auxin efflux carrier genes in Malus genus,
      MdPIN1a and MdPIN1b, which were closely related to the AtPIN1. We found that
      MdPIN1b was expressed preferentially in BC and M9, and the expression of MdPIN1b
      was significantly lower in the phloem of M9 interstem than that in the scion and
      rootstock. The distinct expression of MdPIN1b and IAA content were concentrated
      in the cambium and adjacent xylem or phloem, and MdPIN1b protein was localized on
      cell plasma membrane in onion epidermal cells transiently expressing 35S:MdPIN1b
      GFP fusion protein. Interestingly, an MdPIN1b mutant allele in the promoter
      region upstream of M9 exhibited decreased MdPIN1b expression compared to BC.
      MdPIN1b over-expressing interstem in tobacco exhibited increased polar auxin
      transport. It is proposed that natural allelic differences decreased promoter
      activity is closely associated with lower MdPIN1b expression in the M9 interstem,
      which might limit the basipetal transport of auxin, and in turn might contribute
      to the dwarfing effect. Taken together, these results reveal allelic variation
      underlying an important apple rootstock trait, and specifically a novel molecular
      genetic mechanism underlying dwarfing mechanism.

PMID- 29340954
TI  - The Cultural Epigenesis of Gender-Based Violence in Cambodia: Local and Buddhist
      Perspectives.
AB  - Almost one in four women in Cambodia is a victim of physical, emotional or sexual
      violence. The study aims to provide a comprehensive understanding of the ways in
      which Cambodians see its causes and effects and to identify and analyse the
      cultural forces that underpin and shape its landscape. An ethnographic study was
      carried out with 102 perpetrators and survivors of emotional, physical and sexual
      violence against women and 228 key informants from the Buddhist and healing
      sectors. Their views and experiences of it were recorded-the popular idioms
      expressed and the symptoms of distress experienced by survivors and perpetrators.
      From these results, the eight cultural forces, or cultural attractors, that are
      seen to propel a person to violence were identified. Violence stemmed from
      blighted endowment, or 'bad building' (salphamnaan min l?alphaalpha) determined
      by deeds in a previous life (kam). Children with a vicious character (kmeen kaac
      or dosa-carita) might grow to be abusers, and particular birthmarks on boys were
      thought to be portents. Krupsiloneh, or mishap, especially when a female's
      horoscope predicted a zodiac house on the descent (riesey), explained
      vulnerability to violence and its timing. Astrological incompatibility (kuu kam)
      was a risk factor. Lust, anger and ignorance, the 'Triple Poison', fuelled it.
      'Entering the road to ruin' (apayamuk), including alcohol abuse, womanising and
      gambling, triggered it. Confusion and loss of judgement (moha) led to moral
      blindness (mo ban). These were the eight cultural attractors that shaped the
      landscape of violence against women. The cultural epigenesis of violence against
      women in Cambodia is an insight which can be used to build culturally responsive
      interventions and strengthen the primary prevention of violence against women. An
      understanding of the epigenesis of violence could strengthen the primary
      prevention of violence against women.

PMID- 29340955
TI  - Adult Atopic Dermatitis is Associated with Increased Aortic Stiffness.

PMID- 29340956
TI  - Semi-Targeted Analysis of Complex Matrices by ESI FT-ICR MS or How an
      Experimental Bias may be Used as an Analytical Tool.
AB  - Ammonia is well suited to favor deprotonation process in electrospray ionization
      mass spectrometry (ESI-MS) to increase the formation of [M - H]-. Nevertheless,
      NH3 may react with carbonyl compounds (aldehyde, ketone) and bias the composition
      description of the investigated sample. This is of significant importance in the
      study of complex mixture such as oil or bio-oil. To assess the ability of primary
      amines to form imines with carbonyl compounds during the ESI-MS process, two
      aldehydes (vanillin and cinnamaldehyde) and two ketones (butyrophenone and
      trihydroxyacetophenone) have been infused in an ESI source with ammonia and two
      different amines (aniline and 3-chloronaniline). The (+) ESI-MS analyses have
      demonstrated the formation of imine whatever the considered carbonyl compound and
      the used primary amine, the structure of which was extensively studied by tandem
      mass spectrometry. Thus, it has been established that the addition of ammonia, in
      the solution infused in an ESI source, may alter the composition description of a
      complex mixture and leads to misinterpretations due to the formation of imines.
      Nevertheless, this experimental bias can be used to identify the carbonyl
      compounds in a pyrolysis bio-oil. As we demonstrated, infusion of the bio-oil
      with 3-chloroaniline in ESI source leads to specifically derivatized carbonyl
      compounds. Thanks to their chlorine isotopic pattern and the high mass
      measurement accuracy, (+) ESI Fourier transform ion cyclotron resonance mass
      spectrometry (FT-ICR MS) unambiguously highlighted them from the numerous CxHyOz
      bio-oil components. These results offer a new perspective into the detailed
      molecular structure of complex mixtures such as bio-oils. Graphical Abstract ?.

PMID- 29340957
TI  - Spontaneous Isomerization of Peptide Cation Radicals Following Electron Transfer
      Dissociation Revealed by UV-Vis Photodissociation Action Spectroscopy.
AB  - Peptide cation radicals of the z-type were produced by electron transfer
      dissociation (ETD) of peptide dications and studied by UV-Vis photodissociation
      (UVPD) action spectroscopy. Cation radicals containing the Asp (D), Asn (N), Glu
      (E), and Gln (Q) residues were found to spontaneously isomerize by hydrogen atom
      migrations upon ETD. Canonical N-terminal [z4 + H]+? fragment ion-radicals of the
      R-C?H-CONH- type, initially formed by N-Calpha bond cleavage, were found to be
      minor components of the stable ion fraction. Vibronically broadened UV-Vis
      absorption spectra were calculated by time-dependent density functional theory
      for several [?DAAR + H]+ isomers and used to assign structures to the action
      spectra. The potential energy surface of [?DAAR + H]+ isomers was mapped by ab
      initio and density functional theory calculations that revealed multiple
      isomerization pathways by hydrogen atom migrations. The transition-state energies
      for the isomerizations were found to be lower than the dissociation thresholds,
      accounting for the isomerization in non-dissociating ions. The facile
      isomerization in [?XAAR + H]+ ions (X = D, N, E, and Q) was attributed to low
      energy intermediates having the radical defect in the side chain that can promote
      hydrogen migration along backbone Calpha positions. A similar side-chain mediated
      mechanism is suggested for the facile intermolecular hydrogen migration between
      the c- and [z + H]?-ETD fragments containing Asp, Asn, Glu, and Gln residues.
      Graphical Abstract ?.

PMID- 29340958
TI  - Robert C. Dunbar (June 26, 1943-October 31, 2017).

PMID- 29340959
TI  - Matrix Assisted and/or Laser Desorption Ionization Quadrupole Ion Trap Time-of
      Flight Mass Spectrometry of WO3 Clusters Formation in Gas Phase. Nanodiamonds,
      Fullerene, and Graphene Oxide Matrices.
AB  - The formation of W x O y+?/-? clusters in the gas phase was studied by laser
      desorption ionization (LDI) and matrix assisted laser desorption ionization
      (MALDI) of solid WO3. LDI produced (WO3) n+ ?/- ? (n = 1-7) clusters. In MALDI,
      when using nano-diamonds (NDs), graphene oxide (GO), or fullerene (C60) matrices,
      higher mass clusters were generated. In addition to (WO3) n-? clusters, oxygen
      rich or -deficient species were found in both LDI and MALDI (with the total
      number of clusters exceeding one hundred ~ 137). This is the first time that such
      matrices have been used for the generation of(WO3) n+?/-? clusters in the gas
      phase, while new high mass clusters (WO3) n-? (n = 12-19) were also detected.
      Graphical Abstract.

PMID- 29340960
TI  - Higher levels of progranulin in cerebrospinal fluid of patients with lymphoma and
      carcinoma with CNS metastasis.
AB  - Assessing central nervous system (CNS) involvement in patients with lymphoma or
      carcinoma is important in determining therapy and prognosis. Progranulin (PGRN)
      is a secreted glycosylated protein with roles in cancer growth and survival; it
      is highly expressed in aggressive cancer cell lines and specimens from many
      cancer types. We examined PRGN levels by Enzyme Immuno-Assay (EIA) in
      cerebrospinal fluid (CSF) samples from 230 patients, including 18 with lymphoma
      [12 with CNS metastasis (CNS+); 6 without CNS metastasis (CNS-)], 21 with
      carcinomas (10 CNS+; 11 CNS-), and 191 control patients with non-cancer
      neurological diseases, and compared PRGN levels among these disease groups.
      Median CSF PGRN levels in the CNS+ lymphoma group were significantly higher than
      in the CNS- lymphoma and control non-cancer groups; and were also significantly
      higher in the CNS+ carcinoma group than in the CNS- carcinoma and control groups,
      except for patients with infectious neurological disorders. Receiver operating
      characteristic curve analyses revealed that CSF PGRN levels distinguished CNS+
      lymphoma from CNS- lymphoma and non-cancer neurological diseases [area under
      curve (AUC): 0.969]; and distinguished CNS+ carcinomas from CNS- carcinomas and
      non-cancer neurological diseases (AUC: 0.918). We report here, for the first
      time, that CSF PGRN levels are higher in patients with CNS+ lymphoma and
      carcinomas compared to corresponding CNS- diseases. This would imply that
      measuring CSF PGRN levels could be used to monitor CNS+ lymphoma and metastasis.

PMID- 29340961
TI  - Metabolic syndrome and its components among Korean submariners: a retrospective
      cross-sectional study.
AB  - PURPOSE: Metabolic syndrome (MetS) is a cluster of inter-related risk factors for
      cardiovascular disease and diabetes. Although submariners tend to be exposed to
      unhealthy environmental factors, such as a confined work environment, physical
      inactivity, and circadian disruption, little is known regarding whether the risks
      of MetS and its components are associated with submarine service. The present
      study aimed to evaluate the risks of MetS and its components among submariners.
      METHODS: A total of 5090 subjects (513 submariners and 4577 non-submariners) were
      included in the present study. We calculated the age-standardized and age
      specific prevalences of MetS. The associations between submarine service and the
      risks of MetS and its components were evaluated using logistic regression
      analysis after adjusting for age, service rank, and lifestyle factors. RESULTS:
      The age-standardized prevalences of MetS were 17.6 and 15.1% among submariners
      and non-submariners, respectively. Compared to non-submariners, submariners had
      higher risks of MetS (odds ratio [OR] 1.31, 95% confidence interval [CI] 1.02,
      1.68), low high-density lipoprotein cholesterol (OR 1.73, 95% CI 1.36, 2.20), and
      impaired fasting glucose (OR 1.46, 95% CI 1.21, 1.76). When we stratified the
      subjects according to physical activity, an increased risk of elevated blood
      pressure associated with submarine service was evident only in the subgroup with
      moderate or vigorous physical activity (P for interaction = 0.006). CONCLUSION:
      Submariners had higher risks of MetS and some MetS components, compared to non
      submariners. These findings suggest that special efforts are needed to prevent
      and manage MetS among individuals who are expected to be exposed to submarine
      environment.

PMID- 29340962
TI  - Apoptotic and proliferative indexes in esophageal cancer: Predictors of response
      to neoadjuvant therapy apoptosis and proliferation in esophageal cancer.
AB  - Altered expression of the genes that control apoptosis and proliferation may
      influence the response of cancer cells to cytotoxic agents. The primary aim of
      this study was to determine the role of the novel an-tiapoptotic and cell cycle
      gene, survivin, in apoptotsis and proliferation in esophageal cancer and to
      evaluate whether the survivin, p53, and bcl-2 status were able to predict a
      patient's response to neoadjuvant therapy. A total of 104 patients with
      esophageal tumors were studied. Tumor tissue was immunostained for survivin, p53,
      and bcl-2 proteins. Proliferative and apoptotic activity was measured using ki-67
      immu-nohistochemical analysis and the TUNEL method, respectively. Forty-eight
      patients whose pretreat-ment biopsies were analyzed received neoadjuvant
      chemoradiation therapy or chemotherapy followed by surgery. Outcome was graded as
      a complete response, a partial response, or no response according to the results
      of histologic examination and CT imaging. Expression of survivin was found to
      correlate significantly with the proliferative index but not the apoptotic index.
      Patients who received neoadjuvant treatment were more likely to achieve a
      complete response if their tumors had high proliferative activity, and p53
      positive tumors were more likely to contain residual tumor after treatment. In
      conclusion, survivin expression appears to foster proliferative activity in
      esophageal cancer, and tumors with a high proliferative index or a functioning
      p53 gene are more responsive to neoadjuvant chemoradiation therapy.

PMID- 29340963
TI  - Interactions between drugs and geriatric syndromes in nursing home and home care:
      results from Shelter and IBenC projects.
AB  - AIM: Drugs may interact with geriatric syndromes by playing a role in the
      continuation, recurrence or worsening of these conditions. Aim of this study is
      to assess the prevalence of interactions between drugs and three common geriatric
      syndromes (delirium, falls and urinary incontinence) among older adults in
      nursing home and home care in Europe. METHODS: We performed a cross-sectional
      multicenter study among 4023 nursing home residents participating in the Services
      and Health for Elderly in Long-TERm care (Shelter) project and 1469 home care
      patients participating in the Identifying best practices for care-dependent
      elderly by Benchmarking Costs and outcomes of community care (IBenC) project.
      Exposure to interactions between drugs and geriatric syndromes was assessed by
      2015 Beers criteria. RESULTS: 790/4023 (19.6%) residents in the Shelter Project
      and 179/1469 (12.2%) home care patients in the IBenC Project presented with one
      or more drug interactions with geriatric syndromes. In the Shelter project,
      288/373 (77.2%) residents experiencing a fall, 429/659 (65.1%) presenting with
      delirium and 180/2765 (6.5%) with urinary incontinence were on one or more
      interacting drugs. In the IBenC project, 78/172 (45.3%) participants experiencing
      a fall, 80/182 (44.0%) presenting with delirium and 36/504 (7.1%) with urinary
      incontinence were on one or more interacting drugs. CONCLUSION: Drug-geriatric
      syndromes interactions are common in long-term care patients. Future studies and
      interventions aimed at improving pharmacological prescription in the long-term
      care setting should assess not only drug-drug and drug-disease interactions, but
      also interactions involving geriatric syndromes.

PMID- 29340964
TI  - Geriatric nutritional risk index as a simple tool for assessment of malnutrition
      among geriatrics in Northwest of Iran: comparison with mini nutritional
      assessment.
AB  - BACKGROUND: Older people are more likely to develop nutritional problems and
      timely diagnosis of malnutrition is crucial to prevent hazardous consequences
      following poor nutrition. AIMS: To evaluate the efficacy of Geriatric Nutritional
      Risk Index (GNRI) to assess nutritional status among non-hospitalized elderly,
      compared to mini nutritional assessment (MNA) among Iranian seniors. METHODS: One
      hundred and sixty-four subjects, aged >= 65 years old were recruited to our cross
      sectional study from various districts of Tabriz (Tabriz, Iran). Anthropometric
      and biochemical measurements were performed, short- and long-form MNAs and GNRI
      were assessed in our study subjects. Sensitivity, specificity and predictive
      values of the three indices, agreement between them, and their correlation with
      anthropometric and biochemical parameters were evaluated. Receiver-operating
      characteristic (ROC) curve analysis was performed to determine the optimal cut
      off point for GNRI in our study population. RESULTS: GNRI had lower sensitivity
      (50, 57%), but optimal specificity (94, 93%) and lower negative predictive value
      (NPV; 68, 71%) compared to MNA-LF and MNA-SF, respectively. We found a moderate
      agreement between GNRI and MNA-SF (K = 0.52) and MNA-LF (K = 0.46) scores.
      Significant correlations were observed between re-categorized MNAs as well as
      GNRI scores, and age, weight, MAC, CC, WC, albumin, and pre-albumin. The cut-off
      point of 110.33 was obtained for GNRI, according to the ROC curve. CONCLUSIONS:
      Although GNRI may not be an efficient tool for screening malnutrition due to its
      lower sensitivity, it is moderately correlated with MNAs and also more useful
      when limited funding needs to target the truly malnourished seniors.

PMID- 29340965
TI  - Emotional and social characteristics of stroke patients with low verbal memory.
AB  - BACKGROUND: Cognitive deficits, especially problems with memory observed after
      stroke often coexist with patients' experience of difficulties in everyday life
      situations. AIMS: The purposes of the study were to explore the relationships
      between verbal memory, emotional functioning and social competence in stroke
      patients, and to examine the emotional and social condition of stroke patients
      with low verbal memory. METHODS: Ninety-five participants were assessed with the
      Rey Auditory Verbal Learning Test, the Neuropsychology Behavior and Affect
      Profile, and the Social Competency Questionnaire. The participants' relatives (N
      = 95) also took part in the study evaluating patients' emotional and social
      functioning. RESULTS: Stroke patients with low verbal memory had higher scores in
      depression, indifference, and inappropriateness than the patients with normal
      memory. They also obtained higher scores in the self-reported intimacy and lower
      scores in objectively assessed social exposition than controls. DISCUSSION: It is
      worth considering patients' relationships with relatives that evolve after
      stroke, especially when the patients experience cognitive difficulties in gaining
      new information. Collecting verbal information seems to be important for the
      feeling of effectiveness in some dimensions of elders' social functioning.
      CONCLUSIONS: Because the social engagement may be treated as protective factor in
      the course of recovery we would recommend that during rehabilitation more
      attention should be paid to emotional and social functioning of stroke patients
      with low verbal memory.

PMID- 29340966
TI  - Cannabinomimetric Lipids: From Natural Extract to Artificial Synthesis.
AB  - Endocannabinoid system is related with various physiological and cognitive
      processes including fertility, pregnancy, during pre- and postnatal development,
      pain-sensation, mood, appetite, and memory. In the latest decades, an important
      milestone concerning the endocannabinoid system was the discovery of the
      existence of the cannabinoid receptors CB1 and CB2. Anandamide was the first
      reported endogenous metabolite, which adjusted the release of some
      neurotransmitters through binding to the CB1 or CB2 receptors. Then a series of
      cannabinomimetric lipids were extracted from marine organisms, which possessed
      similar structure with anandamide. This review will provide a short account about
      cannabinomimetric lipids for their extraction and synthesis.

PMID- 29340967
TI  - Testing the actual equivalence of automatically generated items.
AB  - If the automatic item generation is used for generating test items, the question
      of how the equivalence among different instances may be tested is fundamental to
      assure an accurate assessment. In the present research, the question was dealt by
      using the knowledge space theory framework. Two different ways of considering the
      equivalence among instances are proposed: The former is at a deterministic level
      and it requires that all the instances of an item template must belong to exactly
      the same knowledge states; the latter adds a probabilistic level to the
      deterministic one. The former type of equivalence can be modeled by using the
      BLIM with a knowledge structure assuming equally informative instances; the
      latter can be modeled by a constrained BLIM. This model assumes equality
      constraints among the error parameters of the equivalent instances. An approach
      is proposed for testing the equivalence among instances, which is based on a
      series of model comparisons. A simulation study and an empirical application show
      the viability of the approach.

PMID- 29340968
TI  - A novel blink detection method based on pupillometry noise.
AB  - Pupillometry (or the measurement of pupil size) is commonly used as an index of
      cognitive load and arousal. Pupil size data are recorded using eyetracking
      devices that provide an output containing pupil size at various points in time.
      During blinks the eyetracking device loses track of the pupil, resulting in
      missing values in the output file. The missing-sample time window is preceded and
      followed by a sharp change in the recorded pupil size, due to the opening and
      closing of the eyelids. This eyelid signal can create artificial effects if it is
      not removed from the data. Thus, accurate detection of the onset and the offset
      of blinks is necessary for pupil size analysis. Although there are several
      approaches to detecting and removing blinks from the data, most of these
      approaches do not remove the eyelid signal or can result in a relatively large
      amount of data loss. The present work suggests a novel blink detection algorithm
      based on the fluctuations that characterize pupil data. These fluctuations
      ("noise") result from measurement error produced by the eyetracker device. Our
      algorithm finds the onset and offset of the blinks on the basis of this
      fluctuation pattern and its distinctiveness from the eyelid signal. By comparing
      our algorithm to three other common blink detection methods and to results from
      two independent human raters, we demonstrate the effectiveness of our algorithm
      in detecting blink onset and offset. The algorithm's code and example files for
      processing multiple eye blinks are freely available for download (
      https://osf.io/jyz43 ).

PMID- 29340969
TI  - On the predictive validity of various corpus-based frequency norms in L2 English
      lexical processing.
AB  - The predictive validity of various corpus-based frequency norms in first-language
      lexical processing has been intensively investigated in previous research, but
      less attention has been paid to this issue in second-language (L2) processing. To
      bridge the gap, in the present study we took English as a case in point and
      compared the predictive power of a large set of corpus-based frequency norms for
      the performance of an L2 English visual lexical decision task (LDT). Our results
      showed that, in general, the frequency norms from SUBTLEX-US and WorldLex-Blog
      tended to predict L2 performance better in reaction times, whereas the frequency
      norms from corpora with a mixture of written and spoken genres (CELEX, WorldLex
      Blog, BNC, ANC, and COCA) tended to predict L2 accuracy better. Although
      replicated in both low- and high-proficiency L2 English learners, these patterns
      were not exactly the same as those found in LDT data from native English
      speakers. In addition, we only observed some limited advantages of the lemma
      frequency and contextual diversity measures over the wordform frequency measure
      in predicting L2 lexical processing. The results of the present study, especially
      the detailed comparisons among the different corpora, provide methodological
      implications for future L2 lexical research.

PMID- 29340970
TI  - Ultrahigh temporal resolution of visual presentation using gaming monitors and G
      Sync.
AB  - Vision unfolds as an intricate pattern of information processing over time.
      Studying vision and visual cognition therefore requires precise manipulations of
      the timing of visual stimulus presentation. Although standard computer display
      technologies offer great accuracy and precision of visual presentation, their
      temporal resolution is limited. This limitation stems from the fact that the
      presentation of rendered stimuli has to wait until the next refresh of the
      computer screen. We present a novel method for presenting visual stimuli with
      ultrahigh temporal resolution (<1 ms) on newly available gaming monitors. The
      method capitalizes on the G-Sync technology, which allows for presenting stimuli
      as soon as they have been rendered by the computer's graphics card, without
      having to wait for the next screen refresh. We provide software implementations
      in the three programming languages C++, Python (using PsychoPy2), and Matlab
      (using Psychtoolbox3). For all implementations, we confirmed the ultrahigh
      temporal resolution of visual presentation with external measurements by using a
      photodiode. Moreover, a psychophysical experiment revealed that the ultrahigh
      temporal resolution impacts on human visual performance. Specifically, observers'
      object recognition performance improved over fine-grained increases of object
      presentation duration in a theoretically predicted way. Taken together, the
      present study shows that the G-Sync-based presentation method enables researchers
      to investigate visual processes whose data patterns were concealed by the low
      temporal resolution of previous technologies. Therefore, this new presentation
      method may be a valuable tool for experimental psychologists and neuroscientists
      studying vision and its temporal characteristics.

PMID- 29340971
TI  - Denosumab or oral bisphosphonates in primary osteoporosis: a "real-life" study.
AB  - PURPOSE: To compare the response to denosumab (DMAb) therapy with that of oral
      bisphosphonate (BISPH) treatment in postmenopausal women with primary
      osteoporosis (PO). METHODS: In this retrospective study, we compared data of 75
      PO female patients treated for 24 months with DMab (DMAb Group, age 72.6 +/- 8.9
      years) with those of 75 PO patients treated with oral bisphosphonates (BISPH
      Group), matched for age, body mass index, femoral bone mineral density (BMD),
      prevalent fragility fractures and familiar history of hip fracture. In all
      subjects at baseline and after 24 months we assessed the calcium-phosphorous
      metabolism parameters, BMD at lumbar spine (LS-BMD) and femoral neck (FN-BMD) by
      dual X-ray absorptiometry and the morphometric vertebral fractures by radiograph.
      The patients were considered inadequate responders in the presence of >= 2
      incident fragility fractures and/or a decrease in BMD greater than the least
      significant change (LS 2.8%, FN 5.9%). RESULTS: After 24 months, the DMab Group
      showed a greater ALP decrease (- 22.8 +/- 18.2%), a higher LS-BMD and FN-BMD
      increase (6.6 +/- 6.9 and 4.4 +/- 8.2%, respectively) and a lower number of
      patients with an incident fracture (8%) and with an inadequate response (6.7%)
      than BISPH Group (- 14.9 +/- 15.3, 2.5 +/- 4.3, 1.9 +/- 4.5, 21.3 and 22.7%,
      respectively, p < 0.05 for all comparisons). The inadequate response was 4.5-fold
      more likely in BISPH Group than in DMab one (p = 0.027), regardless of possible
      confounders. CONCLUSIONS: In postmenopausal PO females, denosumab was more
      effective than oral bisphosphonates in increasing BMD and reducing bone turnover
      and the number of inadequate responder patients.

PMID- 29340972
TI  - Presence of diabetes-specific autoimmunity in women with gestational diabetes
      mellitus (GDM) predicts impaired glucose regulation at follow-up.
AB  - PURPOSE: Gestational diabetes mellitus (GDM) is the most frequent complication of
      pregnancy; around 10% of GDM cases may be determined by autoimmunity, and our
      aims were to establish the role of autoimmunity in a population of Sardinian
      women affected by GDM, to find predictive factors for autoimmune GDM, and to
      determine type 1 diabetes (T1D) auto-antibodies (Aabs) together with glucose
      tolerance after a mean 21.2 months of follow-up. METHODS: We consecutively
      recruited 143 women affected by GDM and 60 without GDM; clinical data and
      pregnancy outcomes were obtained by outpatient visit or phone recall. T1D auto
      antibodies GADA, IA2-A, IAA, ZnT8-A were measured in the whole population at
      baseline, and in the Aab-positive women at follow-up. RESULTS: The overall
      prevalence of autoimmunity was 6.4% (13/203). No significant difference was found
      in the prevalence of auto-antibodies between GDM (5.6%) and control (8.3%) women,
      neither in antibody titres. Highest titres for GADA and ZnT8-A were observed in
      the control group; no phenotypic factors were predictive for autoimmune GDM.
      Diabetes-related autoantibodies were still present in all the GDM women at follow
      up, and their presence was associated with a 2.65 (p < 0.0016) relative risk (RR)
      of glucose impairment. CONCLUSION: We observed a low prevalence (5.6%) of
      diabetes-related autoimmunity in our GDM cohort, consistent with the prevalence
      reported in previous studies. It was not possible to uncover features predictive
      of autoimmune GDM. However, given the significant risk of a persistent impaired
      glycemic regulation at follow-up, it is advisable to control for glucose
      tolerance in GDM women with diabetes-related autoimmunity.

PMID- 29340973
TI  - Reference intervals for thyrotropin in an area of Northern Italy: the Pordenone
      thyroid study (TRIPP).
AB  - PURPOSE: Thyrotropin (TSH) is the most accurate marker of thyroid dysfunction in
      the absence of pituitary or hypothalamic disease. Studies on TSH reference
      intervals (RIs) showed wide inter-individual variability and prompted an intense
      debate about the best estimation of TSH RIs. DESIGN: We performed a population
      study on TSH RIs, using current data stored in the laboratory information system
      (LIS), at the Hospital Department of Laboratory Medicine, Pordenone (Italy),
      historically an area of mild-moderate iodine deficiency with a relatively high
      goiter prevalence. METHODS: 136,650 individuals constituted the final sample. A
      TSH immunoassay was performed on fasting serum samples with the Dimension Vista
      1500 analyzer (Siemens Healthineers). We adopted the Kairisto's procedure to
      analyze TSH data downloaded by the LIS, applying the indirect strategy for
      deriving RIs. RESULTS: TSH RIs of the entire population were 0.32-3.36 mIU/L with
      a distribution skewed towards higher values. RIs were 0.26-3.61 mIU/L for
      females, and 0.32-3.01 mIU/L for males. Unlike other studies, TSH median levels
      progressively decreased from 0-4 to 85-104 years in the overall population, both
      in male and in female subgroups, showing an inverse correlation between TSH and
      age in all groups. CONCLUSIONS: This study is the first to analyze a high
      percentage (40%) of individuals from an ethnically homogenous Caucasian
      population. The results obtained emphasize the opportunity to define the TSH RIs
      according to age, gender and race, in addition to assay methods, and provide
      further insight about the possible role of iodine status.

PMID- 29340974
TI  - Inhibiting 6-phosphogluconate dehydrogenase selectively targets breast cancer
      through AMPK activation.
AB  - PURPOSE: 6-phosphogluconate dehydrogenase (6PGD), a key enzyme of the oxidative
      pentose phosphate pathway, is involved in tumor growth and metabolism. Although
      high 6PGD activity has been shown to be associated with poor prognosis, its role
      and therapeutic value in breast cancer remain unknown. METHODS: The levels and
      roles of 6PGD were analyzed in breast cancer cells and their normal counterparts.
      The underlying mechanisms of 6PGD's roles are also analyzed. RESULTS: We found
      that 6PGD is aberrantly activated in breast cancer as shown by its increased
      transcriptional and translational levels as well as enzyme activity in breast
      cancer tissues and cell lines compared to normal counterparts. Although similar
      degree of enzyme activity inhibition was achieved in both breast cancer and
      normal breast cells, 6PGD inhibition by siRNA-mediated knockdown or
      pharmacological inhibitor physcion is more effective in inhibiting growth and
      survival in breast cancer than normal breast cells. Moreover, inhibiting 6PGD
      significantly sensitizes breast cancer response to chemotherapeutic agents in in
      vitro cell culture system and in vivo xenograft breast cancer model. We further
      show that 6PGD inhibition activates AMPK and its downstream substrate ACC1,
      leading to reduction of ACC1 activity and lipid biosynthesis. AMPK depletion
      significantly reverses the inhibitory effects of physcion in breast cancer cells,
      confirming that 6PGD inhibition targets breast cancer cell via AMPK activation.
      CONCLUSIONS: Our work provides experimental evidence on the association of 6PGD
      with poor prognosis in breast cancer and suggests that 6PGD inhibition may
      represent a potential therapeutic strategy to augment chemotherapy efficacy in
      breast cancer.

PMID- 29340975
TI  - Epidemiology of injuries in tennis players.
AB  - PURPOSE OF REVIEW: To review the recent literature regarding the epidemiology of
      tennis injuries at all levels of play, and to discuss recent findings in injury
      surveillance by the Association of Tennis Professionals (ATP). RECENT FINDINGS:
      Following the release of a consensus statement in 2009 calling for standardized
      documentation and analysis of tennis-related injuries, multiple studies have been
      published describing longitudinal injury incidences at Grand Slam tournaments and
      the Davis Cup. Recent efforts by the ATP have further elucidated injury patterns
      on tour. There have also been recent high-quality studies on injury trends among
      collegiate and elite junior tennis players, bringing attention to musculoskeletal
      injuries and systemic illnesses that young tennis players may be susceptible to.
      Recent efforts in injury surveillance by the ATP and at the collegiate and junior
      levels have highlighted injury trends that will help guide injury prevention
      strategies at various levels of play.

PMID- 29340976
TI  - Erratum to: Apoptotic and proliferative indexes in esophageal cancer: Predictors
      of response to neoadjuvant therapy apoptosis and proliferation in esophageal
      cancer.

PMID- 29340977
TI  - New Strategies for Improving the Development and Performance of Amorphous Solid
      Dispersions.
AB  - The understanding of amorphous solid dispersions has grown significantly in the
      past decade. This is evident from the number of approved commercial amorphous
      solid dispersion products. While amorphous formulation is considered an enabling
      technology, it has become the norm for formulating poorly soluble compounds.
      Despite this success, improvements can still be made that enable early
      development formulation decisions, to develop a rationale for selecting a
      manufacturing process, to overcome degradation and phase separation during
      processing, to help achieve physical stability during storage, and to optimize
      dissolution behavior. The purpose of this literature review is to present
      recently reported strategies for improving the development and performance of
      ASDs. The benefits and limitations of each strategy as well as recent relevant
      case studies will be presented in this review. The strategies are presented from
      three different aspects: (a) prediction techniques that enable formulation
      decisions, (b) manufacturing considerations that help produce physically and
      chemically stable ASDs, and

PMID- 29340978
TI  - Methotrexate Aspasomes Against Rheumatoid Arthritis: Optimized Hydrogel Loaded
      Liposomal Formulation with In Vivo Evaluation in Wistar Rats.
AB  - Aspasomes of methotrexate with antioxidant, ascorbyl palmitate, were developed
      and optimized using factorial design by varying parameters such as lipid molar
      ratio, drug to lipid molar ratio, and type of hydration buffer for transdermal
      delivery for disease modifying activity in rheumatoid arthritis (RA). Aspasomes
      were characterized by drug-excipients interaction, particle size analysis,
      determination of zeta potential, entrapment efficiency, and surface properties.
      The best formulation was loaded into hydrogel for evaluation of in vitro drug
      release and tested in vivo against adjuvant induced arthritis model in wistar
      rats, by assessing various physiological, biochemical, hematological, and
      histopathological parameters. Optimized aspasome formulation exhibited smooth
      surface with particle size 386.8 nm, high drug loading (19.41%), negative surface
      potential, and controlled drug release in vitro over 24 h with a steady
      permeation rate. Transdermal application of methotrexate-loaded aspasome hydrogel
      for 12 days reduced rat paw diameter (21.25%), SGOT (40.43%), SGPT (54.75%),
      TNFalpha (33.99%), IL beta (34.79%), cartilage damage (84.41%), inflammation
      (82.37%), panus formation (84.38%), and bone resorption (80.52%) as compared to
      arthritic control rats. Free methotrexate-treated group showed intermediate
      effects. However, drug-free aspasome treatment did not show any effect. The
      experimental results indicate a positive outcome in development of drug-loaded
      therapeutically active carrier system which presents a non-invasive controlled
      release transdermal formulation with good drug loading, drug permeation rate, and
      having better disease modifications against RA than the free drug, thereby
      providing a more attractive therapeutic strategy for rheumatoid disease
      management.

PMID- 29340979
TI  - Effect of Moisture Content of Chitin-Calcium Silicate on Rate of Degradation of
      Cefotaxime Sodium.
AB  - Assessment of incompatibilities between active pharmaceutical ingredient and
      pharmaceutical excipients is an important part of preformulation studies. The
      objective of the work was to assess the effect of moisture content of chitin
      calcium silicate of two size ranges (two specific surface areas) on the rate of
      degradation of cefotaxime sodium. The surface area of the excipient was
      determined using adsorption method. The effect of moisture content of a given
      size range on the stability of the drug was determined at 40 degrees C in the
      solid state. The moisture content was determined at the beginning and the end of
      the kinetic study using TGA. The degradation in solution was studied for
      comparison. Increasing the moisture content of the excipient of size range 63-180
      MUm (surface area 7.2 m2/g) from 3.88 to 8.06% increased the rate of degradation
      of the drug more than two times (from 0.0317 to 0.0718 h-1). While an opposite
      trend was observed for the excipient of size range < 63 MUm (surface area 55.4
      m2/g). The rate of degradation at moisture content < 3% was 0.4547 h-1, almost
      two times higher than that (0.2594 h-1) at moisture content of 8.54%, and the
      degradation in solid state at both moisture contents was higher than that in
      solution (0.0871 h-1). In conclusion, the rate of degradation in solid should be
      studied taking into consideration the specific surface area and moisture content
      of the excipient at the storage condition and it may be higher than that in
      solution.

PMID- 29340980
TI  - Facile Synthesis of Chitosan Capped Mesoporous Silica Nanoparticles: A pH
      Responsive Smart Delivery Platform for Raloxifene Hydrochloride.
AB  - An encapsulation of model drug raloxifene hydrochloride (RAL) inside the chitosan
      decorated pH responsive mesoporous system has a greater potential for
      accumulating in the tumor cells. The present study involves synthesis of surface
      modified mesoporous silica nanoparticles (MSN) with the aim of achieving pH
      sensitive drug delivery system. A silanol skeleton of MSN has been productively
      modified to amine intermediate which served as a firm platform to adapt chitosan
      grafted assembly and systematically evaluated. RAL incorporation inside the
      featured mesopores was performed employing novel immersion solvent evaporation
      methodology and evaluated further. The pH responsive behavior of formulated nano
      framework was studied at three different pH of a phosphate buffer saline
      individually. The in vitro cell viability assay on MCF-7 breast carcinoma cells
      was performed in time and concentration dependent manner. Finally, the hemolysis
      assay of designed nanoparticle was accomplished to envisage the
      hemocompatibility. The outcome of characterization details unveiled a perfect 2D
      hexagonal spherical structure gifted with higher surface area and optimum pore
      size for designed nanoparticles. The higher percentage grafting of amine and
      chitosan residue, i.e., 4.01 and 28.51% respectively along with 31.89 and 33.57%
      RAL loading efficiency made MSNs more attractive and applicable. Eventually, in
      vitro release study exhibited higher RAL release in acidic media for extended
      time periods confirming successful formation of pH responsive nanoparticle having
      controlled release property. Conclusively potential of designed nanosystem to
      serve efficient anti-cancer remedy was confirmed by superior behaviour of
      chitosan grafted MSN towards MCF-7 cells with supreme hemocompatibility.

PMID- 29340981
TI  - Nanolipid Gel of an Antimycotic Drug for Treating Vulvovaginal Candidiasis
      Development and Evaluation.
AB  - This paper focuses on the development and evaluation of mucoadhesive vaginal gel
      of fluconazole using nanolipid carriers to enhance tissue deposition in treating
      vulvovaginal candidiasis. Treatment of vulvovaginal candidiasis includes
      antimycotic agents prescribed for 1 to 7 days or longer, in relapse either orally
      or topically. The delivery of fluconazole as nanolipid carriers in vaginal gel
      can be proposed as suitable alternative to the existing conventional formulations
      to improve the patient acceptability, compliance and localized drug action. The
      nanolipid carriers of fluconazole were prepared by phase inversion temperature
      technique and incorporated into Carbopol 974P as gelling polymer. GRAS excipients
      selected and optimized were Precirol ATO 5, oleic acid and Kolliphor RH 40 to
      produce nanolipid dispersions. Stable nanolipid dispersions were developed using
      sodium dodecyl sulfate as the charge inducer. The optimized nanolipid dispersion
      of fluconazole had particle size, polydispersity index and zeta potential value
      of 158.33 +/- 2.55 nm, 0.278 +/- 0.003 and - 27.33 +/- 0.40 mV, respectively and
      the average entrapment of fluconazole in the lipid carriers was found to be 67.24
      +/- 0.87%. The optimized vaginal gel had satisfactory mucoadhesive strength and
      rheological properties to facilitate vaginal application. The fluconazole release
      from the gel was sustained showing 30.69 +/- 1.02% drug deposition in the porcine
      vaginal mucosa at the end of 8 h with improved antifungal activity against
      Candida albicans during well diffusion studies. The optimized gel was non
      irritant to the vaginal mucosa of female Wistar rats with no signs of erythema or
      edema.

PMID- 29340982
TI  - Controlled Release of the Nimodipine-Loaded Self-Microemulsion Osmotic Pump
      Capsules: Development and Characterization.
AB  - The present study was intended to develop a controlled released osmotic pump
      capsule based on Nimodipine (NM)-loaded self-microemulsifying drug delivery
      systems (SMEDDSs) in order to improve the low oral bioavailability of NM. To
      optimize the NM-loaded SMEDDS composition, the experiments of NM solubility in
      different oils, the pseudo-ternary phase diagram experiments and the different
      drug loading experiments were conducted in the preliminary screening studies.
      Controlled release of NM required an osmotic pump capsule comprising a coated
      semi-permeable capsule shell, plasticizer, and pore-forming agent. NM release
      follows zero-order kinetics after oral administration. Polyethylene glycol
      content, used as a pore-forming agent, coating mass, and drug release orifice
      size were key factors affecting drug release behavior according to the single
      methods and were optimized through response surface methodology. The NM-loaded
      SMEDDS droplet size and the 1H NMR mass spectrogram of the novel capsule were
      determined. The droplet size of the reconstituted microemulsion was 39.9 nm and
      1H NMR analysis showed NM dissolution in the microemulsion. The dissolution test
      performed on three batches of NM-SMEDDS capsules-prepared using optimal
      preparation methods-indicated the capsule to deliver a qualified drug delivery
      with a zero-order release rate. The results demonstrated that NM-loaded SMEDDSs
      were successfully developed and displayed a qualified release rate in vitro.

PMID- 29340983
TI  - 18F-FDG PET/CT-imaging of left ventricular assist device infection: a
      retrospective quantitative intrapatient analysis.
AB  - BACKGROUND: Despite the use of 18F-fluorodeoxyglucose (18F-FDG) positron emission
      tomography/computed tomography (PET/CT), diagnosis of a driveline infection in
      ventricular assist device (LVAD) recipients remains challenging. Our aim was to
      evaluate the potential of a baseline 18F-FDG PET/CT (prior to an infection) for
      the diagnosis of an LVAD-related infection. METHODS: We retrospectively selected
      all LVAD recipients who had undergone two consecutive whole-body 18F-FDG PET/CT
      examinations between January 2010 and December 2016. PET/CT was analyzed
      qualitatively (uptake pattern) and semi-quantitatively (SUVmax and ?SUVmax).
      SUVmax was measured and compared in five distinctive volumes of interest along
      the LVAD driveline. An SUVmax threshold was calculated. Final diagnosis was made
      by clinical examination, microbiological parameters, and molecular imaging.
      RESULTS: Thirty patients were enrolled (mean age 54 +/- 12 years; 26 male). Mean
      difference in SUVmax for all five positions between the first and the second
      PET/CT along the driveline was significantly higher in patients with an LVAD
      related infection (mean ?SUVmax = 4.38 +/- 1.44) compared to those without a
      driveline infection (mean ?SUVmax = 0.03 +/- 0.43), P < 0.05. Applying ROC
      analysis, an SUVmax threshold of 3.88 resulted in a sensitivity and specificity
      of 100%, respectively. There were three distinctive uptake patterns in patients
      with a driveline infection. CONCLUSION: PET/CT diagnosis in the context of an
      LVAD-related infection can be improved by comparison to a baseline examination
      using a distinctive SUVmax threshold.

PMID- 29340984
TI  - Exercise-induced ST elevation with minimal ischemia by perfusion imaging.

PMID- 29340985
TI  - The mystery poor prognosticator! Pharmacologic stress MPI prevalence and
      predictors: Insights from the Middle East.

PMID- 29340986
TI  - Comparison of maximal Rubidium-82 activities for myocardial blood flow
      quantification between digital and conventional PET systems.
AB  - BACKGROUND: PET-based myocardial blood flow (MBF) quantification can be
      inaccurate when using high tracer activities. Our aim was to derive the maximal
      Rubidium-82 activity for MBF assessment using a new digital PET system and
      compare the results with conventional analog systems. METHODS: 1.8 GBq Rubidium
      82 was injected into the cardiac insert of an anthropomorphic torso phantom. Data
      were acquired for 10 min using an Ingenuity TF (Philips Healthcare), Discovery
      690 (D690, GE Healthcare), and digital PET prototype system (Philips Healthcare).
      The dynamic ranges, defined as the maximal measured activity in the reconstructed
      images deviating < 10% from the true present activity, were determined in all
      scans. RESULTS: The dynamic ranges were 312 MBq for Ingenuity TF, 650 MBq for
      D690, and 654 MBq for digital PET prototype. CONCLUSIONS: The maximal Rb-82
      activity for MBF assessment using digital PET prototype is higher than that for
      its analog counterpart (Ingenuity TF), but seems comparable to the D690.

PMID- 29340987
TI  - Lost in quantification...: The influence of different software packages on flow
      quantification measures.

PMID- 29340988
TI  - Interventricular septum involvement with complete atrioventricular block as first
      manifestation in Takayasu arteritis.

PMID- 29340989
TI  - Gated SPECT myocardial perfusion imaging with cadmium-zinc-telluride detectors
      allows real-time assessment of dobutamine-stress-induced wall motion
      abnormalities.
AB  - BACKGROUND: Left ventricular (LV) ejection fraction (EF) during high dobutamine
      stress (HD) by real-time gated-SPECT myocardial perfusion imaging (MPI) on a
      cadmium-zinc-telluride (CZT) gamma camera was validated versus cardiac magnetic
      resonance imaging (CMR). METHODS AND RESULTS: After injecting 99mTc-tetrofosmin
      (320 MBq) in 50 patients (mean age 64 +/- 11 years), EF at rest and post-stress
      as well as relevant changes in EF at HD (DeltaEF >= 5%) were assessed. CZT and
      CMR rest EF values yielded an excellent correlation and agreement (r = 0.96; P <
      0.001; Bland-Altman limits of agreement (BA): + 0 to 14.8%). HD EF acquisition
      was feasible using CZT and correlated better to HD CMR EF than did post-stress
      CZT EF (r = 0.85 vs 0.76, respectively, all P < 0.001). Agreement in DeltaEF
      detection between HD CMR and immediate post-stress CZT (reflecting standard
      acquisition using conventional SPECT camera unable to scan during stress) was
      45%, while this increased to 85% with real-time HD CZT scan. CONCLUSION: Real
      time ultrafast dobutamine gated-SPECT MPI with a CZT device is feasible and
      provides accurate measurements of HD LV performance.

PMID- 29340990
TI  - Role of myocardial perfusion scintigraphy in octogenarians: Time for reappraisal?

PMID- 29340991
TI  - Neoadjuvant Chemotherapy for Hypopharyngeal Squamous Cell Carcinoma and
      Personalized Medicine in Head and Neck Cancer.

PMID- 29340992
TI  - Prospective Comparative Study of Laparoscopic Narrow Band Imaging (NBI) Versus
      Standard Imaging in Gynecologic Oncology.
AB  - BACKGROUND: Narrow band imaging (NBI) is an optic filtration enhancement for
      endoscopy that uses two wavelengths of light (415 and 540 nm) to highlight
      superficial microvascular patterns. It has been successfully utilized to improve
      identification of lesions with abnormal vasculature, which is associated with
      endometriosis and endometrial cancer. Case studies suggest it may also facilitate
      surgical staging of gynecologic cancer, which is critical in determining
      appropriate adjuvant therapies. A technology that enhances the ability to
      identify metastatic disease during minimally invasive surgery (MIS) could make an
      important difference in patient outcomes. METHODS: A prospective comparative
      study was conducted to evaluate patients with clinical indication for diagnostic
      or operative laparoscopy. All received white light imaging followed by NBI during
      the same procedure. Suspicious lesions were examined and photographed, using both
      modalities, before excision. The two techniques were compared. Positive
      predictive value, negative predictive value, and diagnostic accuracy in
      identifying histologically confirmed metastatic lesions were assessed, using
      appropriate statistical methods. RESULTS: Of 124 patients enrolled in the study,
      94 were evaluable; 30 did not undergo MIS and were therefore excluded. A
      significantly higher number of peritoneal abnormalities were identified with NBI
      versus white light imaging (P = 0.0239). However, no statistically significant
      difference (P = 0.18, patient level) was observed in identification of
      histologically confirmed metastatic disease. CONCLUSIONS: NBI imaging provides a
      unique contrast between peritoneal surface and microvascular patterns. However,
      the results of this study suggest that NBI-enhanced laparoscopy does not provide
      superior detection of peritoneal surface malignancy compared with standard white
      light high-definition laparoscopy.

PMID- 29340993
TI  - Laparoscopic-Assisted Modified Intersphincter Resection for Ultralow Rectal
      Cancer.
AB  - BACKGROUND: Intersphincter resection (ISR) is considered to be a superior
      technique offering sphincter preservation in patients with ultralow rectal
      cancer.1 Because high-definition laparoscopy offers wider and clearer vision into
      the narrow pelvic cavity and intersphincteric space, ISR has been further
      refined.2 However, functional outcome after ISR has not been optimal. More than
      half of patients receiving ISR suffer partial or even complete anal
      incontinence.3 We therefore propose a laparoscopic-assisted modified ISR, with
      the aim of improving sphincter function following ISR. METHODS: The video
      describes the technique for performing such laparoscopic-assisted modified ISR in
      a 62-year-old woman with ultralow rectal cancer (3 cm from anal verge).
      Preoperative staging by endorectal ultrasound and pelvic magnetic resonance
      imaging revealed stage I rectal cancer (cT2N0M0). The operation consisted of an
      abdominal and a perineal phase. The abdominal phase routinely involved colonic
      mobilization with high ligation of inferior mesenteric vessels, total mesorectal
      excision (TME), as well as transabdominal intersphincteric dissection. The
      procedure for laparoscopic TME was performed according to our published method.4
      Along the TME dissection plane, the puborectalis could be reached and the
      intersphincteric space was entered posterolaterally. The hiatal ligament at the
      posterior side of the rectum was transected afterwards. The dissection of the
      intersphincteric space was continued caudally at the anterior side of the rectum.
      The distal bowel wall was mobilized for 2 cm from the lower edge of the tumor to
      obtain adequate distal margin. At this point, circular dissection of the
      intersphincteric space was completed. After the abdominal phase, perineal
      dissection was performed with wide exposure by use of a hooked self-retaining
      retractor. The lower margin of the tumor was identified under direct vision. We
      developed a modified ISR technique. Resection of the mucosa and internal
      sphincter was initiated 2 cm distal to the lower edge of the tumor at the tumor
      side to obtain the necessary distal margin. Meanwhile, at the opposite side of
      the tumor, the resection line was just above the dentate line so that partial
      dentate line could be preserved. After removal of the specimen en bloc per anus,
      the pelvic cavity was generously irrigated with diluted povidone iodine
      solutions. The distal margin of the specimen was then examined by frozen section
      for presence of cancer. If clear, coloanal anastomosis was performed using a
      handsewn technique. The colon was rotated 90 degrees  and anastomosed to the anal
      canal with interrupted absorbable 3-0 sutures. Finally, a pelvic suction drain
      was placed, and a temporary diverting stoma made in the terminal ileum. RESULTS:
      There were no intraoperative complications. The operating time was 180 min. Blood
      loss was 50 mL. The distal margin was clear, and the final pathology was pT2N0M0.
      The patient underwent an uneventful recovery. She began sphincter-strengthening
      exercises 2 weeks after surgery. The stoma was closed after examinations 3 months
      later. No local recurrence or distant metastasis was found. At 12-month follow
      up, in terms of sphincteric function, the patient was continent to solids,
      liquids, and flatus. CONCLUSIONS: Laparoscopic-assisted modified intersphincter
      resection for ultralow rectal cancer is safe and feasible. This technique should
      be considered whenever possible as a means to offer sphincter preservation and
      improve sphincter function in patients with ultralow rectal cancer.

PMID- 29340994
TI  - Erratum to: Detection of Ultrafine Anaphase Bridges.

PMID- 29340995
TI  - Is bacteremia the decisive factor for the duration of antimicrobial therapy in
      bacteremic urinary tract infections?

PMID- 29340996
TI  - Recent advances in the development of polycyclic skeletons via Ugi reaction
      cascades.
AB  - Isocyanide-based multicomponent reactions are among the most powerful synthetic
      tools available. Particularly, the isocyanide-based Ugi reaction can allow rapid
      preparation of [Formula: see text]-aminoacyl amide derivatives and
      polyazaheterocycles with extensive pharmaceutical applications. Moreover, bridged
      polyazaheterocycles, including one or more quaternary carbon centers, can be
      constructed via the Ugi cascade reaction in a few steps. This review will
      emphasize synthesis and bioactivities of bridged compounds with quaternary
      centers constructed through Ugi cascade reactions.

PMID- 29340998
TI  - On pacing trials while scanning brain hemodynamics: The case of the SNARC effect.
AB  - Experimental designs used to describe psychological effects on overt human
      behavior are seldom suited to localize their corresponding neural substrates
      based on the analysis of stimulus-evoked brain hemodynamic responses. This is
      because stimuli in behavioral studies are usually separated by intertrial
      intervals (ITIs) in the order of 1 second or so following a behavioral response,
      which is notoriously too brief a time to detect a corresponding hemodynamic
      response. In fact, a solution commonly adopted in neuroimaging studies is to
      prolong the ITI up to several seconds. In doing so, the consequences of ITI
      variations between behavioral and neuroimaging design variants are either
      benignly neglected or explicitly assumed to be negligible. Here, we provide a
      systematic investigation of the consequence of manipulating ITI in a design
      optimized to study a well-established and highly replicable psychological
      phenomenon-the spatial numerical association of response codes (SNARC). The
      present exploration encompassed standard estimates of the SNARC effect (i.e., on
      reaction times and accuracy), estimates of ITI effects on the emotional state of
      participants before and after performing the SNARC task, as well as the degree of
      perceived task difficulty. The results showed that, in striking contrast to the
      common wisdom about the nil role of ITI, the substantial number of parametric
      differences observed between the two ITI conditions suggests that ITI plays a
      critical role in shaping the meaning of hemodynamic correlate of a psychological,
      at least the SNARC, effect.

PMID- 29340999
TI  - Introduction to MRI Physics.
AB  - Magnetic resonance imaging (MRI) is an imaging technique derived from
      radiofrequency (RF) signals of proton that are magnetized by a strong magnetic
      field. These protons typically originate from water, fat, or metabolites. The
      application of RF pulses is used to excite the magnetization, whereas pulsed
      magnetic field gradients are used to provide spatial localization. This chapter
      describes the fundamental principles giving rise to MR images. Furthermore, the
      connection between relaxation and image contrast is discussed.

PMID- 29340997
TI  - Immunohistochemical Biomarkers of Mesenchymal Neoplasms in Endocrine Organs:
      Diagnostic Pitfalls and Recent Discoveries.
AB  - Mesenchymal neoplasms rarely present in or adjacent to endocrine organs. In this
      context, the recognition of these rare tumor types can be challenging, with
      significant potential for misdiagnosis as sarcomatoid carcinomas (i.e.,
      anaplastic thyroid carcinoma and sarcomatoid adrenal cortical carcinoma) or
      neuroendocrine carcinomas, depending upon the dominant histologic patterns. In
      this review, we address potential pitfalls in diagnosing selected mesenchymal
      neoplasms arising within or near endocrine organs, including dedifferentiated
      liposarcoma, synovial sarcoma, angiosarcoma, PEComa, proximal-type epithelioid
      sarcoma, Ewing sarcoma, and neuroblastoma. For each of these tumor types, we
      review clinical and pathologic features, histologic clues to distinguish them
      from endocrine neoplasms, and recently developed immunohistochemical markers that
      can be particularly useful for establishing the correct diagnosis.

PMID- 29341000
TI  - Basic Pulse Sequences in Magnetic Resonance Imaging.
AB  - Magnetic resonance images are obtained by a combination of different
      radiofrequency pulses and gradient waveforms applied to the subject inside a
      magnetic field. There are multiple pulse sequences used in clinical and
      preclinical studies adjusted to whatever physician or researches want to analyze,
      from basic anatomic images to accurate diagnostic techniques as diffusion,
      perfusion, or functional imaging. In this chapter, we present the most used
      radiofrequency pulse combinations of the two groups of sequences available in
      magnetic resonance imaging: spin-echo and gradient-echo sequences.

PMID- 29341001
TI  - Dynamic Susceptibility Contrast MRI in Small Animals.
AB  - The use of magnetic resonance imaging (MRI) for studying the cerebral perfusion
      mechanisms is well proved and contrasted in the clinical and research setups.
      This methodology is a promising tool in assessing numerous brain diseases like
      intracranial tumors, neurodegeneration processes, mental disorders, injuries and
      so on. In the preclinical environment, perfusion MRI offers a powerful resource
      for characterizing pathological models and specially identifying biomarkers to
      monitor the illness and validate the efficacy of therapeutical approaches. This
      chapter presents the theoretical bases and experimental protocols of dynamic
      susceptibility contrast MRI acquisitions for developing perfusion MRI studies in
      small animals.

PMID- 29341002
TI  - Preclinical Arterial Spin Labeling Measurement of Cerebral Blood Flow.
AB  - Magnetic resonance imaging has been utilized as a quantitative and noninvasive
      method to image blood flow. Arterial spin labeling (ASL) is an MRI technique that
      images blood flow using arterial blood water as an endogenous tracer. Herein we
      describe the use of ASL to measure cerebral blood flow completely noninvasively
      in rodents, including methods, analysis, and important considerations when
      utilizing this technique.

PMID- 29341003
TI  - Dynamic Contrast-Enhanced MRI.
AB  - Dynamic contrast-enhanced MRI in pre-clinical imaging allows the in-vivo
      monitoring of vascular, physiological properties in normal and diseased tissue.
      There is considerable variation in the methods employed owing to the different
      questions that can be asked and answered about the physiologic alterations as
      well as morphologic changes in tissue. Here we review the typical decisions in
      the design and execution of a dynamic contrast-enhanced MRI study in mice
      although the findings can easily be transferred to other species. Emphasis is
      placed on highlighting the many pitfalls that wait for the unaware pre-clinical
      MRI practitioner and that go often unmentioned in the abundant literature dealing
      with dynamic contrast-enhanced MRI in animal models.

PMID- 29341004
TI  - Diffusion-Weighted Magnetic Resonance Imaging.
AB  - Magnetic resonance imaging (MRI) is a technique based on the contents and
      relaxation features of water in tissues. In basic MRI sequences, diffusion
      phenomenon of water molecules is not taken into account although it has a notable
      influence in the relaxation times, and therefore in the signal intensity of
      images. In fact, MRI techniques that take advantage of water diffusion have
      experienced a huge development in last years. Diffusion-weighted imaging (DWI)
      has spectacularly evolved reaching nowadays a great impact both in clinical and
      preclinical imaging-especially in the neuroimaging field-and in basic research.
      We present here a protocol to perform DWI studies in a high-field preclinical
      setup.

PMID- 29341005
TI  - Diffusion Tensor Imaging (DTI).
AB  - Diffusion Tensor Imaging is an MRI technique that allows in vivo noninvasive
      measurement of the translational motion of water, providing information about its
      anisotropy (or lack of it) in different tissues. DTI has been commonly used to
      quantitatively measure the integrity of tissues which may be compromised by
      neurological disease, such as white matter tracks of the brain, which normally
      impart significant anisotropy to water motion in healthy brains. However, this
      anisotropic effect is diminished when axonal or neuronal damage is present. This
      chapter describes a standard protocol for DTI data acquisition in preclinical
      studies.

PMID- 29341006
TI  - Mapping Functional Connectivity in the Rodent Brain Using Electric-Stimulation
      fMRI.
AB  - Since its discovery in the early 90s, BOLD signal-based functional Magnetic
      Resonance Imaging (fMRI) has become a fundamental technique for the study of
      brain activity in basic and clinical research. Functional MRI signals provide an
      indirect but robust and quantitative readout of brain activity through the tight
      coupling between cerebral blood flow and neuronal activation, the so-called
      neurovascular coupling. Combined with experimental techniques only available in
      animal models, such as intracerebral micro-stimulation, optogenetics or
      pharmacogenetics, provides a powerful framework to investigate the impact of
      specific circuit manipulations on overall brain dynamics. The purpose of this
      chapter is to provide a comprehensive protocol to measure brain activity using
      fMRI with intracerebral electric micro-stimulation in murine models. Preclinical
      research (especially in rodents) opens the door to very sophisticated and
      informative experiments, but at the same time imposes important constrains (i.e.,
      anesthetics, translatability), some of which will be addressed here.

PMID- 29341007
TI  - Functional Diffusion Magnetic Resonance Imaging.
AB  - Functional diffusion magnetic resonance imaging (fDMRI) is a noninvasive
      technique that allows elucidating physiological and anatomical changes at a
      microscopic scale by detection of water molecular displacements in tissue
      structures. These displacements likely reflect microstructural changes associated
      with neuronal or glial cells activation. In this chapter, we will describe the
      physical and biological concepts of fDMRI and how images of brain activation can
      be acquired in a preclinical setup.

PMID- 29341008
TI  - In Vivo 1H Magnetic Resonance Spectroscopy.
AB  - In vivo Magnetic Resonance Spectroscopy (MRS) allows the non-invasive detection
      and quantification of a number of metabolites from localized volumes within a
      living organism. MRS localization techniques can be divided into two main groups,
      single voxel and multi-voxel. Single voxel techniques provide the metabolic
      profile from a specific small volume, whereas multi-voxel techniques are used to
      obtain the spatial distribution of metabolites throughout a large volume
      subdivided into small contiguous voxels. This chapter describes standard
      protocols for the acquisition and processing of in vivo single voxel1H MRS data
      from the rodent brain.

PMID- 29341009
TI  - In Vivo Heteronuclear Magnetic Resonance Spectroscopy.
AB  - Magnetic Resonance Spectroscopy is a technique that has the capability of
      measuring metabolites in vivo and, in appropriate conditions, to infer its
      metabolic rates. The success of MRS depends a lot on its sensitivity, which
      limits the usage of X-nuclei MRS. However, technological developments and
      refinements in methods have made in vivo heteronuclear MRS possible in humans and
      in small animals. This chapter provides detailed descriptions of the main
      procedures needed to perform successful in vivo heteronuclear MRS experiments,
      with a particular focus on experimental setup in 13C MRS experiments in rodents.

PMID- 29341010
TI  - 1H Spectroscopic Imaging of the Rodent Brain.
AB  - Proton MR spectroscopic imaging (MRSI) can provide a variety of "molecular
      images" from animal models of human disease, which are useful for different
      research purposes. This chapter describes a protocol for in vivo acquisition and
      analysis of MRSI data from the rodent brain.

PMID- 29341011
TI  - Susceptibility Weighted MRI in Rodents at 9.4 T.
AB  - Susceptibility Weighted Imaging (SWI) is an established part of the clinical
      neuroimaging toolbox and, since its inception, has also successfully been used in
      various preclinical studies. Exploiting the effect of variations of magnetic
      susceptibility between different tissues on the externally applied, static,
      homogeneous magnetic field, the method visualizes venous vasculature, hemorrhages
      and blood degradation products, calcifications, and tissue iron deposits. The
      chapter describes in vivo and ex vivo protocols for preclinical SWI in rodents.

PMID- 29341012
TI  - Biomedical 19F MRI Using Perfluorocarbons.
AB  - Background-free fluorine (19F) MR imaging exhibits an excellent degree of
      specificity, and facilitates among others the in vivo visualization of
      inflammatory processes. Merging19F MR images with morphologically matching1H MR
      images enables the exact anatomic localization of the observed19F signal.
      Biochemically inert nanoemulsions of perfluorocarbons, which are known to be
      taken up by the macrophage/monocyte system, are widely used as contrast agents
      for preclinical applications. Herein, the most common protocols are described to
      obtain high-resolution and artifact-free19F MR images even for compounds with
      complex19F MR spectra. In addition, we report on the utilization of
      perfluorocarbons with individual spectral identities and targeting approaches to
      specifically visualize thrombi by19F MRI.

PMID- 29341013
TI  - Rodent Abdominal Adipose Tissue Imaging by MR.
AB  - Rodents including rats and mice are important models to study obesity, diabetes,
      and metabolic syndrome in a preclinical setting. Translational and longitudinal
      imaging of these rodents permit investigation of metabolic diseases and
      identification of imaging biomarkers suitable for clinical translation. Here we
      describe the imaging protocols for achieving quantitative abdominal imaging in
      small animals followed by segmentation and quantification of fat volumes.

PMID- 29341014
TI  - Cardiac MRI in Small Animals.
AB  - Cardiac magnetic resonance (MR) imaging of mice is a valuable tool for the
      precise in vivo diagnosis and prognosis of heart defects. This detailed protocol
      describes the method of cardiac MR imaging in mice step by step. A series of MR
      images captures the contractile function of the mouse heart and post-processing
      of the image data yields morphometric parameters (myocardial mass, myocardial
      wall thickness, ventricular end-systolic and end-diastolic volume) as well as
      functional parameters (stroke volume and ejection fraction). This protocol may
      also serve as a starting point for MR imaging of rats, by using larger image
      dimensions (field-of-view) and MR hardware suitable for larger animals.

PMID- 29341015
TI  - In Utero MRI of Mouse Embryos.
AB  - Genetically engineered mouse models are used extensively as models of human
      development and developmental diseases. Conventional histological approaches are
      static and two-dimensional, and do not provide a full understanding of the
      dynamic, spatiotemporal changes in developing mouse embryos. Magnetic resonance
      imaging (MRI) offers a noninvasive and longitudinal approach for three
      dimensional in utero imaging of normal and mutant mouse embryos. In this chapter,
      we describe MRI approaches that have been developed for imaging the living
      embryonic mouse brain and vasculature. Details are provided on the animal
      preparation and setup, MRI equipment, acquisition and reconstruction methods that
      have been found to be most useful for in utero MRI, including examples of
      applications to fetal mouse neuroimaging.

PMID- 29341016
TI  - Oxygenation Imaging by Nuclear Magnetic Resonance Methods.
AB  - Oxygen monitoring is a topic of exhaustive research due to its central role in
      many biological processes, from energy metabolism to gene regulation. The ability
      to monitor in vivo the physiological distribution and the dynamics of oxygen from
      subcellular to macroscopic levels is a prerequisite to better understand the
      mechanisms associated with both normal and disease states (cancer,
      neurodegeneration, stroke, etc.). This chapter focuses on magnetic resonance
      imaging (MRI) based techniques to assess oxygenation in vivo. The first
      methodology uses injected fluorinated agents to provide quantitative pO2
      measurements with high precision and suitable spatial and temporal resolution for
      many applications. The second method exploits changes in endogenous contrasts,
      i.e., deoxyhemoglobin and oxygen molecules through measurements of T 2* and T 1,
      in response to an intervention to qualitatively evaluate hypoxia and its
      potential modulation.

PMID- 29341017
TI  - Molecular Magnetic Resonance Imaging (mMRI).
AB  - Molecular magnetic resonance imaging (mMRI) enables the detection of a protein of
      interest in vivo, in a noninvasive manner. The general concept of mMRI is to
      target a contrast agent to a protein of interest, and to perform a contrast
      sensitive MRI sequence. Typically, contrast agents are made of a "contrastophore"
      (the part of the construct responsible for the contrast on the images) and a
      targeting moiety ("pharmacophore"). Recently, the development of a new family of
      contrastophore carrying a high payload of iron oxide (micro-sized particles of
      iron oxide, MPIO) has led to a dramatic increase in the sensitivity of mMRI.
      Here, we describe the production of targeted MPIO using commercially available
      reagents and the MRI protocols to allow their detection in vivo.

PMID- 29341018
TI  - Magnetic Resonance Spectroscopy Studies of Mouse Models of Cancer.
AB  - Magnetic resonance spectroscopy (MRS) or spectroscopic imaging (MRSI) enables the
      detection of metabolites, amino acids, and lipids, among other biomolecules, in
      tumors of live mouse models of cancer. Tumor-bearing mice are anesthetized by
      breathing isoflurane in a magnetic resonance (MR) scanner dedicated to small
      animal MR. Here we describe the overall setup and steps for measuring 1H and 31P
      MRS and 1H MRSI of orthotopic breast tumor models in mice with surface coils.
      This protocol can be adapted to the use of volume coils to measure 1H and 31P
      MRS(I) of tumor models that grow inside the body. We address issues of animal
      handling, setting up the measurement, measurement options, and data analysis.

PMID- 29341019
TI  - MRI in the Study of Animal Models of Neurodegenerative Diseases.
AB  - Magnetic Resonance Imaging (MRI) is an important tool to study various animal
      models of degenerative diseases. This chapter describes routine protocols of T 1
      , T 2-, and T 2*-weighted and diffusion-weighted MRI for rodent brain and spinal
      cord. These protocols can be used to measure atrophy, axonal and myelin injury
      and changes in white matter connectivity.

PMID- 29341020
TI  - MRI in the Study of Animal Models of Stroke.
AB  - Stroke consists of the loss of cerebral functions resulting from the interruption
      of blood supply to a region of the brain, and represents the second cause of
      death and the leading cause of major disability in adults in Europe. Stroke is a
      very active field of research at preclinical and clinical levels, and Magnetic
      Resonance Imaging (MRI) is one of the most powerful tools that scientist and
      clinicians have for the study of the onset, evolution and consequences of this
      devastating disease, as well as for the monitoring of the success of available
      treatments, or for the development of novel therapeutic strategies.MRI can tackle
      the study of stroke from different points of view, and at scales ranging from
      subcellular to systems biology level. Magnetic resonance spectroscopy (MRS)
      allows the noninvasive measurement of the levels of principal metabolites in the
      brain, and how they change during the course of the disease, or in response to
      therapy. Glutamate, in particular, is very important in the field of stroke.
      Several anatomical MR techniques allow the characterization of the lesion
      volumes, the formation of cytotoxic and vasogenic edema, changes in cerebral
      blood flow and volume, structural changes in gray and white matter, the obtaining
      of the vascular architecture and status, etc. At functional level, diverse
      modalities of functional MRI (fMRI) allow the assessment of the alteration in the
      function and organization of neuronal networks of the subject under study, as a
      consequence of the disease or in response to treatment. Finally, emerging imaging
      modalities that include temperature and pH mapping of the brain, imaging by
      chemical exchange saturation transfer effect (CEST), all of them closely related
      to tissue status, or the use of contrast agents for the targeting of tissue in
      theranostic approaches or for cell tracking studies in cell-based therapies,
      etc., are only a few examples of the power and versatility of MRI as a definitive
      tool for the study of stroke.In this work we will set our focus on preclinical
      imaging of stroke models, emphasizing the most commonly used imaging modalities
      in a stroke-dedicated research laboratory. However, advanced techniques will be
      briefly discussed, providing references to specialized literature for more
      advanced readers. Thus, the aim of this chapter consist in the description of a
      simple imaging protocol for the study of the most important and common aspects of
      stroke in a research laboratory.

PMID- 29341021
TI  - Assessment of Blood Brain Barrier Leakage with Gadolinium-Enhanced MRI.
AB  - The integrity of the blood-brain barrier (BBB) can be noninvasively monitored by
      magnetic resonance imaging (MRI). Conventional MR contrast agents (CAs)
      containing gadolinium are used in association with MRI in routine clinical
      practice to detect and quantify BBB leakage. Under normal circumstances CAs do
      not cross the intact BBB. However due to their small size they extravasate from
      the blood into the brain tissue even when the BBB is partially compromised. Here
      we describe an MR method based on T1-weighted images taken prior to and after CA
      injection. This MR method is useful for investigating BBB permeability in in vivo
      mouse models and can be easily applied in a number of experimental disease
      conditions including neuroinflammation disorders, or to assess (un)wanted drug
      effects.

PMID- 29341022
TI  - In Vivo Pharmacokinetics of Magnetic Nanoparticles.
AB  - Over the past few years, many papers have been published on the nanomedical
      applications of magnetic nanoparticles. However, most studies lack important
      information about the in vivo behavior of these nanoparticles, which is a
      critical aspect for their rational design. In this chapter we describe a simple
      protocol for the in vivo characterization of the pharmacokinetics of magnetic
      nanoparticles intravenously injected in mice, using basic MRI sequences.

PMID- 29341023
TI  - Anesthesia and Monitoring of Animals During MRI Studies.
AB  - The use of imaging represents a major impact on the refinement and the reduction
      of in vivo studies in animal models, in particular for allowing longitudinal
      monitoring of the onset and the progression of disease within the same animal,
      and studying the biological effects of drug candidate and their therapeutic
      effectiveness. But the use of imaging procedures can affect animal physiology,
      and the need to anesthetize the animals for imaging entails potential health
      risks. During anesthesia, there is an inevitable autonomic nervous system
      depression which induces cardiovascular depression, respiratory depression, and
      hypothermia. Also other procedures associated with imaging such as animal
      preparation (e.g., fasting, premedication), blood sampling, and dosage/contrast
      agent injections can also affect physiology and animal welfare. All these factors
      are likely to have confounding effect on the outcome of the imaging studies and
      pose important concerns regarding the animal's well-being, particularly when
      imaging immune deprived animals or diseased animals. We will discuss these
      challenges and considerations during imaging to maximize efficacious data while
      promoting animal welfare.

PMID- 29341024
TI  - Advanced Contrast Agents for Multimodal Biomedical Imaging Based on
      Nanotechnology.
AB  - Clinical imaging modalities have reached a prominent role in medical diagnosis
      and patient management in the last decades. Different image methodologies as
      Positron Emission Tomography, Single Photon Emission Tomography, X-Rays, or
      Magnetic Resonance Imaging are in continuous evolution to satisfy the increasing
      demands of current medical diagnosis. Progress in these methodologies has been
      favored by the parallel development of increasingly more powerful contrast
      agents. These are molecules that enhance the intrinsic contrast of the images in
      the tissues where they accumulate, revealing noninvasively the presence of
      characteristic molecular targets or differential physiopathological
      microenvironments. The contrast agent field is currently moving to improve the
      performance of these molecules by incorporating the advantages that modern
      nanotechnology offers. These include, mainly, the possibilities to combine
      imaging and therapeutic capabilities over the same theranostic platform or
      improve the targeting efficiency in vivo by molecular engineering of the
      nanostructures. In this review, we provide an introduction to multimodal imaging
      methods in biomedicine, the sub-nanometric imaging agents previously used and the
      development of advanced multimodal and theranostic imaging agents based in
      nanotechnology. We conclude providing some illustrative examples from our own
      laboratories, including recent progress in theranostic formulations of
      magnetoliposomes containing omega-3 poly-unsaturated fatty acids to treat
      inflammatory diseases, or the use of stealth liposomes engineered with a pH
      sensitive nanovalve to release their cargo specifically in the acidic
      extracellular pH microenvironment of tumors.

PMID- 29341025
TI  - Multiple sclerosis: Prevalence and impact.
AB  - This article provides new information about multiple sclerosis (MS) using the
      2010/2011 Neurological Conditions Prevalence File, the 2011/2012 Survey of
      Neurological Conditions in Institutions in Canada, and the 2011 Survey on Living
      with Neurological Conditions in Canada. An estimated 93,500 Canadians living in
      private households and 3,800 residents of long-term care institutions had been
      diagnosed with MS. Prevalence estimates were 159 and 418 cases per 100,000
      population for men and women, respectively; 2.6 women reported MS for every man
      with the condition. Among the household population, MS was generally diagnosed
      between the ages of 20 and 49 (82%). For the majority (68%), MS was their only
      neurological condition. The impact of MS included pain that prevented activities,
      impairments in mobility, cognition or sleep, and limitations in social
      functioning. Almost two-thirds (64%) stated that MS affected their lives at least
      moderately.

PMID- 29341026
TI  - Trends and correlates of frequency of fruit and vegetable consumption, 2007 to
      2014.
AB  - BACKGROUND: Eating fruit and vegetables is recommended as part of a healthy diet.
      This study describes trends in the frequency of fruit and vegetable consumption
      in Canada, the contribution of fruit juice to these trends, and correlates of the
      frequency of fruit and vegetable consumption. DATA AND METHODS: The data are from
      the annual Canadian Community Health Survey for the 2007-to-2014 period and
      pertain to the household population aged 12 or older. Weighted frequencies and
      cross-tabulations were used to estimate the average frequency of fruit and
      vegetable consumption by socio-demographic characteristics and body mass index,
      age-standardized to the 2014 Canadian population. Multivariate logistic
      regressions were used to examine correlates of frequency of fruit and vegetable
      intake in 2014. RESULTS: In 2014, Canadians reported consuming fruit and
      vegetables an average of 4.7 times a day, a slight, but significant, decrease
      from 5.0 times a day in 2007. The decrease over time was no longer significant
      when fruit juice was excluded (dropping to an average of 4.1 times a day in both
      years). Canadians drank less juice in 2014 than in 2007, a decline that was
      apparent across all age, sex and household income quintiles, all regions, and all
      weight categories. In 2014, Canadians who reported consuming fruit and vegetables
      5 or more times a day tended to be female, in younger age groups, in the highest
      household income quintile, and neither overweight nor obese. DISCUSSION: Between
      2007 and 2014, Canadians' reported frequency of fruit and vegetable consumption
      was consistently low. Correlates of fruit and vegetable consumption can be used
      to target nutrition policy and education efforts to improve intake.

PMID- 29341027
TI  - Developing Deep Learning Applications for Life Science and Pharma Industry.
AB  - Deep Learning has boosted artificial intelligence over the past 5 years and is
      seen now as one of the major technological innovation areas, predicted to replace
      lots of repetitive, but complex tasks of human labor within the next decade. It
      is also expected to be 'game changing' for research activities in pharma and life
      sciences, where large sets of similar yet complex data samples are systematically
      analyzed. Deep learning is currently conquering formerly expert domains
      especially in areas requiring perception, previously not amenable to standard
      machine learning. A typical example is the automated analysis of images which are
      typically produced en-masse in many domains, e. g., in high-content screening or
      digital pathology. Deep learning enables to create competitive applications in so
      far defined core domains of 'human intelligence'. Applications of artificial
      intelligence have been enabled in recent years by (i) the massive availability of
      data samples, collected in pharma driven drug programs (='big data') as well as
      (ii) deep learning algorithmic advancements and (iii) increase in compute power.
      Such applications are based on software frameworks with specific strengths and
      weaknesses. Here, we introduce typical applications and underlying frameworks for
      deep learning with a set of practical criteria for developing production ready
      solutions in life science and pharma research. Based on our own experience in
      successfully developing deep learning applications we provide suggestions and a
      baseline for selecting the most suited frameworks for a future-proof and cost
      effective development.

PMID- 29341028
TI  - Ameliorative Effects of Zataria Multiflora Hydro-Alcoholic extract on Gentamicin
      Induced Nephrotoxicity in Rats.
AB  - BACKGROUND: Nephrotoxicity is the major side effects of aminoglycoside
      antibiotics such as gentamicin. The aim of this study was to investigate the
      therapeutic effects of Z.multiflora (ZM) hydroalcoholic extract on gentamicin
      induced nephrotoxicity. METHODS: Twenty-eight male Wistar rats categorized into
      four groups: 1) the control group without injection, 2) the gentamicin treated
      group (100 mg/kg, i.p) 3) the gentamicin and Z. Multiflora treated group; Z.
      Multiflora extract(0.8 mg/ml in the drinking water) administered after gentamicin
      (100 mg/kg, i.p) 4) the normal saline and Z. Multiflora treated group; Z.
      Multiflora extract (0.8 mg/ml in the drinking water) administered after normal
      saline injection (2 ml/kg,i.p ). RESULTS: Post-treatment with ZM extract caused a
      significant reduction in the levels of plasma creatinine and blood urea nitrogen
      (BUN), absolute and fractional excretion of sodium, malondialdehyed (MDA) level
      in comparison to gentamicin group. In addition, ZM extract significantly
      increased creatinine clearance, urine osmolarity, and Renal blood flow (RBF) and
      the Ferric reducing ability of plasma (FRAP) level which had decreased compared
      to the control group as a result of treatment with gentamicin. CONCLUSION: The
      above result indicated that ZM extract improved renal toxicity of gentamicin via
      reducing oxidative stress, oxygen-free radicals, and lipid peroxidation.

PMID- 29341029
TI  - In Vitro and In Situ Absorption and Metabolism of Sesquiterpenes from Petasites
      hybridus Extracts.
AB  - Petasites hybridus extract is used in the treatment of seasonal allergic
      rhinitis. The aim of this study was to evaluate the active constituent petasin
      and its isomers isopetasin and neopetasin (petasins) in the P. hybridus extract
      Ze 339 for liberation, dissolution, absorption, and metabolism. The determination
      of pH-dependent thermodynamic solubility was performed via the shake-flask
      method. Petasins exhibited a low solubility that was pH independent. In vivo, the
      concentration of solute drugs is decreased continuously by intestinal absorption.
      Therefore, low solubility is not assumed to be critical for in vivo performance.
      Additionally, dissolution of an herbal medicinal product containing P. hybridus
      extract Ze 339 was assessed. Furthermore, high permeability through Caco-2
      monolayers was evident. Using an in situ rat model, absorption capacity for
      petasins was found in all tested intestinal segments, namely, duodenum, jejunum,
      and ileum. Besides, high metabolism was evident both in Caco-2 monolayers and in
      the rat intestine. To compare intestinal and hepatic metabolism of petasins, in
      vitro enzyme assays using liver and intestinal cytosol and microsomes (S9
      fraction) of rats and humans were performed. A significantly higher metabolic
      rate was found in the liver S9 fraction of both species compared with the
      intestinal S9 fraction.

PMID- 29341030
TI  - New Tirucallane-Type Triterpenoids from Guarea guidonia.
AB  - The aerial parts of Guarea guidonia afforded three new tirucallane-type
      triterpenoids: 3,4-seco-tirucalla-4(28),8(9),24(25)-trien-7alpha,11alpha
      dihydroxy-21,23-epoxy-3,11-olide, named guareolide (1: ), 3,4-seco-tirucalla
      4(28),7(8),24(25)-trien-21-hydroxy-21,23-epoxy-3-oic acid, named guareoic acid A
      (2: ), and 3,4-seco-tirucalla-4(28),7(8),24(25)-trien-21,23-epoxy-3-oic acid,
      named guareoic acid B (3: ), of which 1: possessed an unusual seven-membered
      lactone ring. Seven known terpenes were also isolated and characterized as
      flindissone, 7-acetyldihydronomilin, picroquassin E, boscartol C, and cneorubins
      A, B, and X. Their structures were determined by spectroscopic methods including
      one-dimensional and two-dimensional nuclear magnetic resonance analysis and high
      resolution mass spectrometry. The isolates were investigated for their potential
      cytotoxic activity on Jurkat, HeLa, and MCF7 cancer cell lines. Flindissone and
      compound 2: showed an antiproliferative activity in all cell lines. Further
      studies revealed that flindissone, the most active compound, induced in Jurkat
      and HeLa cells both cytostatic and cytotoxic responses.

PMID- 29341031
TI  - Getting More Than You Paid For: Unauthorized "Natural" Substances in Herbal Food
      Supplements on EU Market.
AB  - As the population in the industrialized world develops preference for what is
      perceived as a natural and holistic way of disease treatment, the popularity and
      the number of food supplements on the market, including herbal ones, is
      experiencing an unprecedented rise. However, unlike herbal medicinal products,
      intended for treating or preventing disease, current legislation classifies food
      supplements as products intended for achieving nutritional or physiological
      effect and to supplement the normal diet. Accordingly, most food supplements are
      not to be associated with specific health claims. However, either due to the
      subtle suggestions by the producers or the wishful thinking of the consumers,
      certain pharmacological effects from food supplements are often expected.
      Medicinal plants included in food supplements usually do not produce dramatic and
      instant pharmacological effects. Therefore, in order to meet the expectation of
      their customers, some producers have turned to the illicit and dangerous practice
      of adulterating their products with synthetic adulterants, including naturally
      occurring molecules, having the desired activity. Such practice is prevalent in,
      although not limited to, food supplements intended for use as weight-loss aids,
      as well as for sport performance and libido enhancement. The review is focusing
      on naturally occurring alkaloids, phenylethanolamines, and their semi-synthetic
      derivatives in food supplements in the European Union as reported by the Rapid
      Alert System for Food and Feed. Their desired and undesired pharmacological
      effects, as well as the methods for their detection and quantification in food
      supplements, will be reviewed.

PMID- 29341032
TI  - [Epidemiology, Diagnosis and Treatment of Adult Patients with Nosocomial
      Pneumonia - Update 2017 - S3 Guideline of the German Society for Anaesthesiology
      and Intensive Care Medicine, the German Society for Infectious Diseases, the
      German Society for Hygiene and Microbiology, the German Respiratory Society and
      the Paul-Ehrlich-Society for Chemotherapy, the German Radiological Society and
      the Society for Virology].
AB  - Nosocomial pneumonia (HAP) is a frequent complication of hospital care. Most data
      are available on ventilator-associated pneumonia. However, infections on general
      wards are increasing. A central issue are infections with multidrug resistant
      (MDR) pathogens which are difficult to treat in the empirical setting potentially
      leading to inappropriate use of antimicrobial therapy.This guideline update was
      compiled by an interdisciplinary group on the basis of a systematic literature
      review. Recommendations are made according to GRADE giving guidance for the
      diagnosis and treatment of HAP on the basis of quality of evidence and
      benefit/risk ratio.This guideline has two parts. First an update on epidemiology,
      spectrum of pathogens and antimicrobials is provided. In the second part
      recommendations for the management of diagnosis and treatment are given. New
      recommendations with respect to imaging, diagnosis of nosocomial viral pneumonia
      and prolonged infusion of antibacterial drugs have been added. The statements to
      risk factors for infections with MDR pathogens and recommendations for
      monotherapy vs combination therapy have been actualised. The importance of
      structured deescalation concepts and limitation of treatment duration is
      emphasized.

PMID- 29341033
TI  - [Lung Volume Reduction Surgery].
AB  - Lung volume reduction surgery (LVRS) offers improvement in lung function, quality
      of life and even survival in well selected patients with severe emphysema.
      Patients with all types of emphysema morphology can profit from LVRS when certain
      selection criteria are present. Hyperinflation plays a key role in qualifying for
      the procedure. Candidate selection should be performed at high volume centers
      with a multidisciplinary emphysema board. Qualified thoracic surgeons together
      with pulmonologists and radiologists identify the suitable patient considering
      emphysema morphology with its target areas for resection, lung function
      parameters and cardiac comorbidities. This review outlines candidate selection,
      technique and results of LVRS to inform referring physicians how to screen und
      inform their patients.

PMID- 29341034
TI  - Therapeutic Assessment of Vulvar Squamous Intraepithelial Lesions with CO2 Laser
      Vaporization in Immunosuppressed Patients.
AB  - OBJECTIVE:  A vulvar squamous intraepithelial lesion is deemed to be a preceding
      lesion to vulvar cancer, especially in women aged under 40 years, holders of an
      acquired or idiopathic immunosuppression. Several treatments have been used to
      treat these lesions. One of the aesthetically acceptable therapeutic methods is
      the CO2 laser vaporization. METHODS:  In a transversal study, 46 records of
      immunosuppressed women bearing a vulvar low grade and/or high grade squamous
      intraepithelial lesion were selected out of the retrospective analysis, computing
      age, date of record, date of vulvar lesion treatment with CO2 laser, the time
      elapsed between the first and the last visit (in months), the number of visits,
      the presence or absence of condylomatous lesions in other female lower genital
      tract sites and whether or not recurrences and persistence of intraepithelial
      lesions have been noticed during the follow-up. RESULTS:  Patients bearing vulvar
      high-grade squamous intraepithelial lesion and immunosuppressed (serum positive
      for human immunodeficiency virus [HIV] or with solid organs transplantation) have
      shown a higher level of persistence of lesions and a higher chance of having
      other areas of the female lower genital tract involved. CONCLUSION:  While the
      CO2 laser vaporization is the most conservative method for the treatment of
      vulvar high-grade intraepithelial lesions, it is far from being the ideal method,
      due to the intrinsic infection features considered. The possibility of
      persistence, recurrences and spontaneous limited regression indicates that a
      closer surveillance in the long-term treated cases should be considered, in
      special for immunosuppressed patients.

PMID- 29341035
TI  - When an Unexpected Diagnosis Occurs: a Vaginal Premenopausal Sarcoma.
AB  - Vaginal cancer is a rare entity. The evidence on its management resides mostly in
      clinical cases or small case series. Of the histological types, the most frequent
      is the squamous cell carcinoma, followed by adenocarcinoma. But what to do when
      identifying an even more infrequent sarcoma in a premenopausal woman? In this
      study, we describe the case of a 53-year-old woman presenting with metrorrhagia
      for two months, who was evaluated after an intense episode. A necrotic and
      ulcerative vaginal swelling was documented and then submitted to biopsy, which
      revealed a vaginal sarcoma. The patient was referred to radiation therapy with 50
      Gy (aiming to control the symptoms and to cause tumor reduction for posterior
      pelvic exenteration with intraoperative radiotherapy) and developed an extra
      pelvic metastization at the end of the treatment, which caused a fast negative
      outcome. Despite the initial poor prognosis, a chemo-irradiation or primary
      surgery regimen might have achieved (although with greater side effects) a better
      survival. This case-report entails a discussion about the strategies to manage
      vaginal sarcoma in advanced stage and in premenopausal women.

PMID- 29341036
TI  - Zika Virus Infection, Pregnancy and Microcephaly.

PMID- 29341037
TI  - Reply to: Zika Virus Infection, Pregnancy and Microcephaly.

PMID- 29341038
TI  - [The use of Deep Inferior Epigastric Vessels to Revascularise Free Flaps for
      Reconstruction of Complex Oncosurgical Defects of the Thigh and the Abdomen].
AB  - BACKGROUND: The resection of large soft-tissue sarcoma requires reconstruction
      with free flaps. The choice of recipient vessels is crucial for the success of
      surgery. PATIENTS: We report four cases with large soft-tissue sarcomas with
      complex anatomical relationships: two tumors of the thigh surrounding the femoral
      neurovascular structures and two tumors of the abdomen with infiltration of the
      thorax and the abdomen. All cases received multimodal interdisciplinary
      treatment. The anterolateral thigh (ALT) flap and the latissimus dorsi (LD) flap
      were employed twice for defect coverage in this series. In all cases the deep
      inferior epigastric (DIE) vessels were transposed to the subcutaneous compartment
      and used as recipient vessels. RESULTS: The mean duration of surgery was 694 +/-
      149 minutes. The mean weight of the tumor specimen was 3069 +/- 1267 g. Three
      flaps healed primarily and one exhibited a minor necrosis, which was treated by
      excision and secondary suture. There were no cases of abdominal herniation due to
      the transposition of vessels. CONCLUSION: Transposition of DIE-vessels to the
      subcutaneus compartment is a good alternative for free flap revascularisation in
      this patient group. In this position, the vessels are easily accessed and used
      for microsurgery. This technical modification increases the reconstructive
      possibilities in large and previously irradiated surgical defects.

PMID- 29341039
TI  - Covert hepatic encephalopathy leads to distinct alterations in the emotional
      state, independently of MELD-Score.
AB  - BACKGROUND AND AIMS: Covert hepatic encephalopathy impairs many aspects of
      quality of life, although its impact on the emotional state has not been
      evaluated. This study aims to evaluate the impact of covert hepatic
      encephalopathy on the emotional state and which factors are associated with
      changes in the emotional state in patients with cirrhosis. METHODS: This single
      center study included all patients with cirrhosis who underwent the portosystemic
      encephalopathy syndrome (PSE) test, critical flicker frequency, and emotional
      state assessment with the Eigenschaftsworterliste 60-S in 2011. Covert hepatic
      encephalopathy was defined by abnormal PSE. Parametric and non-parametric tests
      were used according to variable distribution. RESULTS: One hundred seventeen
      patients with cirrhosis were included (median age: 59 [interquartile range: 48 -
      67], 32 % female, 74 % alcohol-associated). Seventy patients had covert hepatic
      encephalopathy (60 %) with a higher MELD (16 [interquartile range: 13 - 21], p =
      0.001) and a higher Child-Pugh score (p = 0.003) compared to patients without
      encephalopathy. Patients with covert encephalopathy felt reduced mental activity
      (p = 0.004), lower general well-being (p = 0.001), and reduced extraversion (p =
      0.021). The scores in the negative domains such as general lethargy (p = 0.031)
      and anxiousness/depressiveness (p = 0.033) were higher in patients with covert
      hepatic encephalopathy. There was no correlation between MELD and the emotional
      state. Patients with 2 pathological tests (critical flicker frequency and PSE)
      showed the most distinct alterations in the emotional state in the group of
      patients with covert hepatic encephalopathy. CONCLUSIONS: Patients with covert
      hepatic encephalopathy have an alteration of the emotional state, which is more
      marked in patients with 2 pathological tests. Interestingly, MELD had no impact
      on the emotional state.

PMID- 29341040
TI  - Risk factors for allograft failure in liver transplant recipients.
AB  - BACKGROUND: With regard to quality of life and organ shortage, follow-up after
      liver transplantation (LT) should consider risk factors for allograft failure in
      order to avoid the need for re-LT and to improve the long-term outcome of
      recipients. Therefore, the aim of this study was to explore potential risk
      factors for allograft failure after LT. MATERIAL AND METHODS: A total of 489
      consecutive LT recipients who received follow-up care at the University Hospital
      of Muenster were included in this study. Database research was performed, and
      patient data were retrospectively reviewed. Risk factors related to donor and
      recipient characteristics potentially leading to allograft failure were
      statistically investigated using binary logistic regression analysis. Graft
      failure was determined as graft cirrhosis, need for re-LT because of graft
      dysfunction, and/or allograft-associated death. RESULTS: The mean age of
      recipients at the time of LT was 50.3 +/- 12.4 years, and 64.0 % were male. The
      mean age of donors was 48.7 +/- 15.5 years. Multivariable statistical analysis
      revealed male recipient gender (p = 0.04), hepatitis C virus infection (HCV) (p =
      0.014), hepatocellular carcinoma (HCC) (p = 0.03), biliary complications after LT
      (p < 0.001), pretransplant diabetes mellitus (p = 0.03), and/or marked fibrosis
      in the initial protocol biopsy during follow-up (p = 0.001) to be recipient
      related significant and independent risk factors for allograft failure following
      LT. CONCLUSION: Male recipients, patients who received LT for HCV or HCC, those
      with pretransplant diabetes mellitus, and LT recipients with biliary
      complications are at high risk for allograft failure and thus should be monitored
      closely.

PMID- 29341041
TI  - Screening interval recommendations following a normal colonoscopy in individuals
      with a familial risk of colorectal cancer.
AB  - BACKGROUND: In view of the increased risk of developing colorectal cancer (CRC)
      in individuals with affected first-degree relatives (FDRs), the German evidence
      based S3 guideline recommends having the first screening colonoscopy early and
      then, following a normal examination, repeating it at least every 10 years. The
      aim of this analysis was to explore colonoscopy interval recommendations in
      clinical practice among individuals aged < 55 years with a familial risk of CRC.
      METHODS: We analyzed data from the FRIDA.Frankfurt study. Patients aged 40 - 54
      years with at least 1 reported FDR with CRC (excluding suspected/known hereditary
      cancer syndromes) and a normal colonoscopy result (no findings) were included.
      Data on colonoscopist recommendations for intervals between subsequent
      colonoscopies were extracted from colonoscopy reports. RESULTS: Of 63 reports of
      normal colonoscopies, 20 (32 %) did not include a recommendation on when to
      undergo a further colonoscopy. Of 43 reports with recommendations, 40 (93 %)
      suggested an interval that was shorter than the recommended maximum interval in
      the guideline: 1 (2 %) was for a 3-year interval, 37 (86 %) were for 5-year
      intervals, and 2 (5 %) were for 8-year intervals. CONCLUSIONS: Although the low
      number of cases limits generalizability, the results indicate that recommended
      intervals in clinical practice are considerably shorter than the recommended
      maximum interval in the guideline.

PMID- 29341042
TI  - [Prescription and risks of proton pump inhibitor: fiction and facts].
AB  - There is substantial discussion about inappropriate prescriptions and risks of
      proton pump inhibitor (PPI) therapy. This review critically reviews prescription
      manners regarding PPI both by general practitioners and in hospitals,
      demonstrates exit strategies after prolonged PPI treatment and evaluates
      clinically relevant risks of PPI therapy.

PMID- 29341043
TI  - Can Neonatal Brain MRI be Performed during Active Cooling?
AB  - OBJECTIVE:  Due to logistical constraints, physicians traditionally delay
      diagnostic imaging for neonatal hypoxic-ischemic encephalopathy (HIE) until the
      neonate has completed all 72 hours of therapeutic hypothermia and rewarming. In
      some cases, neonates may require neuroimaging before 72 hours has passed. STUDY
      DESIGN:  We present a case in which an MRI was acquired during active
      hypothermia. RESULTS:  Upon return to the NICU, Baby X's temperature probe read
      33.6 degrees, indicating that hypothermia was likely maintained at the target
      temperature. CONCLUSION:  Active hypothermia is possible during MRI.

PMID- 29341044
TI  - Antenatal Medical Therapies to Improve Lung Development in Congenital
      Diaphragmatic Hernia.
AB  - Congenital diaphragmatic hernia (CDH) is a birth defect characterized by failed
      closure of the diaphragm, allowing abdominal viscera to herniate into the
      thoracic cavity and subsequently impair pulmonary and vascular development.
      Despite improving standardized postnatal management, there remains a population
      of severe CDH for whom postnatal care falls short. In these severe cases,
      antenatal surgical intervention (fetoscopic endoluminal tracheal occlusion
      [FETO]) may improve survival; however, FETO increases the risk of preterm
      delivery, is not widely offered, and still fails in half of cases. Antenatal
      medical therapies that stimulate antenatal pulmonary development are therefore
      interesting alternatives. By presenting the animal research underpinning novel
      antenatal medical therapies for CDH, and considering the applications of these
      therapies to clinical practice, this review will explore the future of antenatal
      CDH management with a focus on the phosphodiesterase-5 inhibitor sildenafil.

PMID- 29341045
TI  - Approach to Infants Born Through Meconium Stained Amniotic Fluid: Evolution Based
      on Evidence?
AB  - Meconium-stained amniotic fluid (MSAF) during delivery is a marker of fetal
      stress. Neonates born through MSAF often need resuscitation and are at risk of
      meconium aspiration syndrome (MAS), air leaks, hypoxic-ischemic encephalopathy,
      extracorporeal membrane oxygenation (ECMO), and death. The neonatal resuscitation
      approach to MSAF has evolved over the last three decades. Previously, nonvigorous
      neonates soon after delivery were suctioned under the vocal cords with direct
      visualization technique using a meconium aspirator. The recent neonatal
      resuscitation program (NRP) recommends against suctioning but favors
      resuscitation with positive pressure ventilation of nonvigorous neonates with
      MSAF. This recommendation is aimed to prevent delay in resuscitation and minimize
      hypoxia-ischemia often associated with MSAF. In this review, we discuss the
      pathophysiology, evolution and the evidence, randomized control trials,
      observational studies, and translational research to support these
      recommendations. The frequency of ECMO use for neonatal respiratory indication of
      MAS has declined over the years probably secondary to improvements in neonatal
      intensive care and reduction of postmaturity. Changes in resuscitation practices
      may have contributed to reduced incidence and severity of MAS. Larger randomized
      controlled studies are needed among nonvigorous infants with MSAF. However,
      ethical dilemmas and loss of equipoise pose a challenge to conduct such studies.

PMID- 29341046
TI  - Reduced Growth Hormone Secretion is Associated with Nonalcoholic Fatty Liver
      Disease in Obese Children.
AB  - The purpose of the study was to evaluate the relationship between arginine
      levodopa-induced growth hormone (GH) secretion and nonalcoholic fatty liver
      disease (NAFLD) in obese children. This study includes a total of 84 obese and 43
      normal weight children. The obese subjects are divided into two groups based on
      the presence or absence of NAFLD. Clinical examination, anthropometric and
      laboratory examinations, and liver ultrasonography are assessed for all
      participants. The obese group had significantly lower peak stimulated GH
      (p<0.001) and lower insulin-like growth factor 1 (IGF-1) (p<0.001) compared with
      the control group. Children with NAFLD had significantly lower peak stimulated GH
      (p<0.001) and lower IGF-1 (p=0.022) compared with non-NAFLD group. Results from
      logistic regression model showed that only peak GH after stimulation test was
      inversely associated with NAFLD (p=0.015), while body mass index (BMI) was
      positively associated with NAFLD (p=0.03). Among 84 obese children and
      adolescents, peak stimulated GH was negatively associated with alanine
      aminotransferase (r=-0.394, p<0.001), BMI (r=-0.571, p<0.001), systolic blood
      pressure (r=-0.223, p=0.041), diastolic blood pressure (r=-0.272, p=0.012),
      homeostasis model assessment of insulin resistance (r=-0.369, p=0.001), insulin
      (r=-0.382, p<0.001), and positively associated with high density lipoprotein
      cholesterol (r=0.275, p=0.011). Our study confirms a significant inverse
      relationship between NAFLD and GH response to standard stimulation testing in
      obese children without known hypothalamic/pituitary disease.

PMID- 29341047
TI  - German Guideline for Idiopathic Pulmonary Fibrosis - Update on Pharmacological
      Therapies 2017.
AB  - Idiopathic pulmonary fibrosis (IPF) is a severe and often fatal disease with a
      median survival of 2 - 4 years after diagnosis. Since the publication of the
      German IPF guideline in 2013 new treatment trials have been published,
      necessitating an update of the pharmacological therapy of IPF. Different from the
      previous guideline, the GRADE system was discarded and replaced by the Oxford
      evidence classification system which allows a more differentiated judgement. The
      following pharmacological therapies were rated not suitable for the treatment of
      IPF patients (recommendation A; evidence 1-b): triple therapy with prednisolone,
      azathioprine and acetyl-cysteine; imatinib; ambrisentan; bosentan; macitentan. A
      less clear but still negative recommendation (B, 1-b) was attributed to the
      treatment of IPF with the phosphodiesterase-5-inhibitor sildenafil and acetyl
      cysteine monotherapy. In contrast to the international guideline antacid therapy
      as a general treatment for IPF was rated negative, based on conflicting results
      of recent analyses (recommendation C; evidence 4). An unanimous positive
      recommendation was granted for the antifibrotic drugs nintedanib and pirfenidone
      for the treatment of IPF (A, 1-a). For some open questions in the management of
      IPF patients for which firm evidence is lacking the guideline also offers
      recommendations based on expert consensus.

PMID- 29341048
TI  - Intrapartum Care Working Patterns of Midwives: The Long Road to Models of Care in
      Germany.
AB  - INTRODUCTION: Midwifery models of care help to enhance perinatal health outcomes,
      women's satisfaction, and continuity of care. Despite the ubiquitous presence of
      certified midwives at births in Germany, no research has investigated the
      diversity of midwives' practice patterns. Describing the variety of working
      patterns through which midwives provide intrapartum care may contribute to
      improving the organisation of midwifery services. METHODS: This cross-sectional
      survey took place in the region of Hannover and Hildesheim, Germany. Midwives
      attending births and practicing in hospitals and/or out-of-hospital were able to
      participate. Midwives who did not attend births were excluded. We assessed
      midwives' scope of services, practice locations, employment patterns, continuity
      of care, midwife-led births, and midwives' level of agreement with core values of
      midwifery care. The response rate of the survey was 32.7 % (69/211). RESULTS: We
      found that midwifery care services can be described according to midwives'
      employment patterns. The majority of midwives were employed in a hospital to
      provide intrapartum care (74.2 %, n = 49), and most also independently offered
      one or more antenatal and/or postpartum service/s. Only 25.8 % (n = 17) of
      midwives offered their services independently (laborist model of care).
      Independent midwives attended births in all three possible settings: hospital,
      free-standing birth centres and home. Significantly more independent midwives
      than employed midwives offered antenatal care and lactation consulting. Compared
      to employed midwives, significantly more independent midwives provided antenatal,
      intrapartum, and postpartum care to the same women, were more likely to know
      women before labour, and to offer one-to-one care during labour. DISCUSSION: The
      most common practice pattern among surveyed midwives was 'employment in a
      hospital' for provision of intrapartum care with additional postpartum and few
      antenatal services provided on an independent basis. Midwives who worked solely
      independently reported more continuity and one-to-one intrapartum care with
      women. Most midwives did not work in patterns that offered continuity of care or
      consistently provide one-to-one care. Future research should assess whether women
      in Germany desire more services similar to caseload midwifery.

PMID- 29341049
TI  - [Long-term Outcome after Prenatal Drug Exposure].
AB  - Although prenatal exposure to opioids, cannabinoids and cocaine is a frequent
      problem, only scarce data have been published on the long-term outcome in
      affected children and adolescents. While opioid-exposed children up to the age of
      2 years show a reduced motor developmental pattern, data from meta-analyses up to
      adolescence show a strong trend for reduced performance with regard to cognitive
      function and behavior. Follow-up data after intrauterine cannabinoid exposure
      indicate reduced cognitive and reading abilities as well as abnormal findings in
      complex planning tests. Externalizing pathologies have been observed more
      frequently in boys. Prenatal cocaine exposure results in reduced cognitive and
      verbal development up to adolescence; however, differences are small but
      significant in meta-analyses. Interpretation of follow-up data with partially
      contradictory results may reflect methodological differences and a number of
      modifying co-factors, e.g., social conditions during the childhood period. These
      data should encourage further primary and secondary preventive attempts.

PMID- 29341050
TI  - [Reading is good for you!]

PMID- 29341051
TI  - [The Journal in 2017].

PMID- 29341052
TI  - [Routine outcome monitoring in anxiety disorders: diagnosis-specific versus
      generic assessment instruments].
AB  - BACKGROUND: Mental health institutions increasingly utilise routine outcome
      monitoring (rom) in order to assess treatment effectiveness. It remains unclear
      which instruments are more sensitive to change with regard to rom in patients
      with an anxiety disorder: diagnosis-specific or generic instruments.<br/> AIM: To
      compare the sensitivity of diagnosis-specific versus generic rom-instruments in
      patients with an anxiety disorder.<br/> METHOD: 160 adults with an anxiety
      disorder received cognitive behavioural therapy at the Altrecht Academic Anxiety
      Centre. Approximately half of the population also received medication. Patients
      completed an assessment both before and after treatment. This consisted of two
      generic instruments (Outcome Questionnaire (oq-45) and Brief Symptom Inventory
      (bsi)) and two diagnosis-specific instruments, determined by the main
      diagnosis.<br/> RESULTS: The differences between pre- and post-treatment
      assessments were generally larger for the generic bsi and diagnosis-specific
      instruments than for the generic oq-45.<br/> CONCLUSION: When assessed after
      cognitive behavioural therapy, the (generic) bsi and diagnosis-specific
      instruments indicated larger progress than the oq-45. The bsi might be a
      relatively diagnosis-specific measure for anxiety disorders. when selecting an
      instrument for assessment, both the intended goal of treatment (symptom reduction
      or improvement in quality of life) and other reasons for assessment should be
      taken into consideration. The bsi or diagnosis-specific instruments are preferred
      if the goal is to assess the change in specific anxiety symptoms.

PMID- 29341053
TI  - [The use of anticonvulsants and the levels of folate, vitamin B12 and
      homocysteine].
AB  - BACKGROUND Patients with epilepsy who use anticonvulsants frequently show low
      levels of folate and vitamin B12 and high levels of homocysteine. Patients with
      bipolar disorder use some anticonvulsants as mood stabilisers.<br/> AIM: To
      determine whether some anticonvulsants lower folate and vitamin B12 and raise
      homocysteine levels.<br/> METHOD: Systematic literature search to determine the
      relation between the anticonvulsants valproic acid, carbamazepine, lamotrigine
      and topiramate on the one hand and blood levels of folate, vitamin B12 and
      homocysteine on the other hand.<br/> RESULTS: The vast majority of studies in
      adults and children showed a correlation between use of anticonvulsant
      carbamazepine and decrease of the folate level. Hardly any of the studies that
      examined the effect of valproic acid on folate levels found a correlation. There
      was next to no evidence of a correlation between the use of carbamazepine and a
      low vitamin B12 level in adults or children. In adults and children the use of
      valproic acid was found to correlate with a higher vitamin B12 level. Nearly all
      studies found an increase in homocysteine in adults and children using
      carbamazepine. Among the users of valproic acid, it was only children who showed
      a clear association with a rise in homocysteine level. The results for adults
      were contradictory. We were unable to make any clear statement about topiramate
      or lamotrigine because there have been very few publications about these
      anticonvulsants.<br/> CONCLUSION: In adults and children with epilepsy use of
      carbamazepine is associated with a decrease of folate, valproic acid with a rise
      in the vitamin B12 level, and carbamazepine with an increase in homocysteine.
      Valproic acid showed only in children an association with the rise of the
      homocysteine level. Psychiatrists may find it advisable to control the levels of
      folate and homocysteine in adults and children who are taking carbamazepine and
      to measure homocysteine level in children taking valproic acid.

PMID- 29341054
TI  - [A relational ethical model for the assessment of decision-making competence in
      psychiatry].
AB  - BACKGROUND: Nowadays, partly due to legislation, decision-making competence is
      playing an ever-increasing role in psychiatry. So far, however, there are no
      clear criteria for evaluating the actual competence of the procedure.<br/> AIM:
      To develop a relational ethical model, including criteria and methodology, which
      can be used to assess and enhance decision-making competence mainly from a
      relational and ethical perspective.<br/> METHOD: Combination of a review of the
      literature and ethical reflection. First of all, a limited study was made of the
      literature relating to the concept of and criteria for decision-making
      competence. On the basis of the literature and relational ethical reflection, ten
      criteria were developed for decision-making competence and a method was devised
      for assessing the procedure.<br/> RESULTS: The criteria that have to be satisfied
      can be summarised as follows: the persons involved must understand the
      information, and must be able to apply it to their own situation. They must be
      able to gain insight into their own situation and be able to weigh up the
      available options, and be able to estimate consequences for themselves, as well
      as for others. They must be able to motivate choices in a sensible and
      comprehensible manner without being subject to coercive influences coming from
      internal and external sources. Participants' choices should be motivated on the
      basis of their own personal values. The decision-making competence is assessed
      and enhanced by giving a score to the individual criteria and by making an
      overall evaluation. This is achieved by a dialogue including all the persons
      involved: the care seeker (as far as possible), close relatives and the care
      providers.<br/> CONCLUSION: The persons involved can attain greater objectivity
      by exchanging views orally on the ten proposed criteria for decision-making
      competence.

PMID- 29341055
TI  - [Hallucinations and art].
AB  - BACKGROUND Hallucinations and art appear to be inextricably connected, and yet
      the question remains in how far artists make use of hallucinations for their work
      in daily practice.<br/> AIM: To chart the ways in which the fine arts are
      influenced by hallucinations, an explorative literature search was carried out.
      METHOD The search was carried out in PubMed, Google, and the historical
      literature.<br/> RESULTS: Some famous examples of artists who drew on
      hallucinations for their work, are Hildegard of Bingen, William Blake, and Yayoi
      Kusama. Especially among the surrealists, we also find indications of the use of
      pareidolias, metamorphopsias, and other positive disorders of visual
      perception.<br/> CONCLUSION: In the art literature, the term hallucination is
      often used in a broader sense than in medicine. As a consequence, the suggestion
      that hallucinations would be lying at the basis of many works of art cannot be
      confirmed, even though some spectacular examples can certainly be pointed out.

PMID- 29341056
TI  - [Researching crisis plans in long-term mental health care: more complicated than
      expected].
AB  - BACKGROUND Crisis plans are highly valued because they can help to reduce the
      number of persons subjected to compulsory treatment in mental health care. The
      evidence however that crisis plans are effective is scarce, partly due to
      insufficient implementation by professionals.<br/> AIM: To assess the fidelity,
      relevance and applicability of crisis plans and to estimate to what extent such
      plans are appreciated by those working in long-term care.<br/> METHOD: Semi
      structured interview with patients and nurses.<br/> RESULTS: The crisis plans
      were judged to be clearly worded and the fidelity was high, but our findings
      cannot be considered as representative because the response rate (12/144; 8.3%)
      of the patients was so low.<br/> CONCLUSION: Despite the accessibility of our
      study design, patient response rates were very low. This demonstrates that
      clinical research in long-term clinical health care clinical research can prove
      to be more complicated than we anticipated. If the research participation rate
      among these very ill and vulnerable population is commonly so low, it will be
      extremely difficult for us to provide evidence-based care for these patients.

PMID- 29341057
TI  - [Suicidal adolescents can benefit from Family Group Conferences].
AB  - A risk factor among suicidal adolescents is generally their inability to form and
      maintain relationships with other people. In the case that we investigated, the
      technique known as Family Group Conference (FGC) was used successfully to break
      through the adolescent's passivity and social isolation. The FGC also helped to
      alter the adolescent's conviction of being a burden to relatives, friends and
      other people. The results are in line with additional studies that used FGC with
      other target groups. This case study suggests that FGC is a promising type of
      intervention that can reduce the passivity and isolation of suicidal adolescents,
      strengthening their relationships and boosting a feeling of belonging. These
      factors as well as the results of the case investigated are currently stimulating
      further research into the use of FGCs to foster feelings of belonging and
      togetherness among suicidal adolescents.

PMID- 29341058
TI  - [Takotsubo cardiomyopathy and catatonia in a patient with psychotic depression].
AB  - Takotsubo cardiomyopathy (tcmp) is an acute, reversible disruption of the left
      ventricular systolic function. In many respects the clinical presentation closely
      resembles acute coronary syndromes (myocardial infarction). tcmp is a syndrome
      with a pathophysiology that is not fully understood and which seems to be closely
      associated with psychiatric disorders or psychological problems. We present a
      case in which a patient with several risk factors developed a tcmp and a
      depression with psychotic features, followed by catatonia. We describe the
      syndrome, make some pathophysiological hypotheses and point to possible
      connections with psychiatric disorders and psychological factors.

PMID- 29341059
TI  - Down-regulated REIC expression in lung carcinogenesis: a molecular target for
      gene therapy.
AB  - REIC (Reduced Expression in Immortalized Cells) gene is down-regulated in
      immortalized cells, compared with the normal parental counterparts. Its encoding
      protein could inhibit colony formation, tumor growth, and induce apoptosis. To
      investigate the roles of REIC expression in lung cancer, we examined REIC
      expression in lung cancer cells and tissues by RT-PCR or Western blot, and
      observed the effects of both recombinant REIC exposure and REIC overexpression on
      the aggressive phenotypes of lung cancer cells. It was found that the
      demethylation of REIC promoter by 5-Aza-dC could reserve its mRNA expression in
      lung cancer cells (P<0.05). There was a lower REIC mRNA expression in lung cancer
      than that in matched normal tissue (P<0.05). Recombinant REIC treatment enhanced
      the proliferation of lung cancer cells (P<0.05), but versa for REIC
      overexpression (P<0.05). Both recombinant REIC treatment and REIC overexpression
      induced apoptosis, and inhibited the migration and invasion of SQ-5 and KJ cells
      (P<0.05). Immunohistochemically, there was a positive correlation between REIC
      and Caspase-3 expression in lung cancer (P<0.05). According to Kaplan-Meier
      plotter, REIC mRNA overexpression was found to positively correlate with overall,
      progression-free and post- progression survival rates of lung cancer patients
      (P<0.05), even stratified by sex, histological subtyping, grading, TNM staging,
      chemotherapy, radiotherapy, or smoking. These findings suggested that the down
      regulated REIC expression might be involved in lung carcinogenesis due to its
      promoter methylation. Both recombinant REIC exposure and REIC overexpression
      might reverse the aggressive phenotypes of lung cancer cells. REIC may be
      employed as a potential target of gene therapy for lung cancer.

PMID- 29341060
TI  - Rationale of decreasing low-density lipoprotein cholesterol below 70 mg/dL in
      patients with coronary artery disease: A retrospective virtual histology.
      Intravascular ultrasound study.
AB  - BACKGROUND: The associations between statin and coronary plaque compositional
      changes were reported according to the use of high dose or not. An evaluation of
      the impact of low-density lipoprotein cholesterol (LDL-C) < 70 mg/dL by using
      real world dosages of statin on coronary plaque composition was undertaken.
      METHODS: The study subjects consisted of 61 patients (mean 59.9 years old, 45
      males) who underwent percutaneous coronary intervention, baseline and follow-up
      (F/U; mean 8.4 months) virtual histology-intravascular ultrasound (VH-IVUS)
      examination. Change of plaque composition at peri-stent area, which was selected
      in order to measure the identical site at F/U study, was compared according to
      the F/U LDL-C level. RESULTS: Body mass index, prevalence of dyslipidemia,
      baseline total cholesterol and baseline LDL-C were significantly lower in F/U LDL
      C < 70 mg/dL group (14 segments in 10 patients) than F/U LDL-C ? 70 mg/dL group
      (79 segments in 51 patients). F/U high-density lipoprotein cholesterol (HDL-C, OR
      1.06, 95% CI 1.00-1.11, p = 0.054) and F/U LDL-C < 70 mg/dL (OR 3.43, 95% CI 0.97
      12.17, p = 0.056) showed strong tendency of regression of necrotic core volume
      (NCV) >= 10%. In multivariable logistic regression analysis, F/U HDL-C (OR 1.07,
      95% CI 1.01-1.14, p = 0.020) and F/U LDL-C level < 70 mg/dL (OR 8.02, 95% CI 1.58
      40.68, p = 0.012) were the independent factors for regression of NCV ? 10%.
      CONCLUSIONS: F/U LDL-C level < 70 mg/dL with any types of statins and increase of
      HDL-C were associated with regression of NCV ? 10% in patients with coronary
      artery disease.

PMID- 29341061
TI  - Pericardial effusion unrelated to surgery is a predictor of mortality in heart
      transplant patients.
AB  - BACKGROUND: Hemodynamically irrelevant pericardial effusion (PeEf) is a predictor
      of adverse outcome in heart failure patients. The clinical relevance of a PeEf
      unrelated to surgery in heart transplant patients remains unknown. This study
      assesses the prognostic value of PeEf occurring later than one year after
      transplantation. METHODS: All patients undergoing heart transplantation in Zurich
      between 1989 and 2012 were screened. Cox proportional hazard models were used to
      analyse mortality (primary) and hospitalization (secondary endpoint). PeEf time
      points were compared to baseline for rejection, immunosuppressants, tumours,
      inflammation, heart failure, kidney function, hemodynamic, and echocardiographic
      parameters. RESULTS: Of 152 patients (mean age 48.3 +/- 11.9), 25 developed PeEf.
      Median follow-up period was 11.9 (IQR 5.8-17) years. The number of deaths was 6
      in the PeEf group and 46 in the non-PeEf group. The occurrence of PeEf was
      associated with a 2.5-fold increased risk of death (HR 2.49, 95% CI 1.02-6.13, p
      = 0.046) and hospitalization (HR 2.53, 95% CI 1.57-4.1, p = 0.0002). CONCLUSIONS:
      This study reveals that the finding of hemodynamically irrelevant PeEf in heart
      transplant patients is a predictor of adverse outcome, suggesting that a careful
      clinical assessment is warranted in heart transplant patients exhibiting small
      PeEf.

PMID- 29341062
TI  - Reflectance confocal microscopy for the diagnosis of Langerhans cell
      histiocytosis.

PMID- 29341063
TI  - Localized inflammatory reactions at sites of subcutaneous methotrexate injections
      during treatment with ultraviolet B.

PMID- 29341064
TI  - Can Addressing Personality Change Enhance Cognitive Functioning and Delay
      Development of Mild Cognitive Impairment?

PMID- 29341065
TI  - The use of methotrexate in adolescents: contraception, confidentiality and
      consent.

PMID- 29341066
TI  - Cerebral near-infrared spectroscopy (NIRS) for perioperative monitoring of brain
      oxygenation in children and adults.
AB  - BACKGROUND: Various techniques have been employed for the early detection of
      perioperative cerebral ischaemia and hypoxia. Cerebral near-infrared spectroscopy
      (NIRS) is increasingly used in this clinical scenario to monitor brain
      oxygenation. However, it is unknown whether perioperative cerebral NIRS
      monitoring and the subsequent treatment strategies are of benefit to patients.
      OBJECTIVES: To assess the effects of perioperative cerebral NIRS monitoring and
      corresponding treatment strategies in adults and children, compared with blinded
      or no cerebral oxygenation monitoring, or cerebral oxygenation monitoring based
      on non-NIRS technologies, on the detection of cerebral oxygen desaturation events
      (CDEs), neurological outcomes, non-neurological outcomes and socioeconomic impact
      (including cost of hospitalization and length of hospital stay). SEARCH METHODS:
      We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2016,
      Issue 12), Embase (1974 to 20 December 2016) and MEDLINE (PubMed) (1975 to 20
      December 2016). We also searched the World Health Organization (WHO)
      International Clinical Trials Registry Platform for ongoing studies on 20
      December 2016. We updated this search in November 2017, but these results have
      not yet been incorporated in the review. We imposed no language restriction.
      SELECTION CRITERIA: We included all relevant randomized controlled trials (RCTs)
      dealing with the use of cerebral NIRS in the perioperative setting (during the
      operation and within 72 hours after the operation), including the operating room,
      the postanaesthesia care unit and the intensive care unit. DATA COLLECTION AND
      ANALYSIS: Two authors independently selected studies, assessed risk of bias and
      extracted data. For binary outcomes, we calculated the risk ratio (RR) and its
      95% confidence interval (CI). For continuous data, we estimated the mean
      difference (MD) between groups and its 95% CI. As we expected clinical and
      methodological heterogeneity between studies, we employed a random-effects model
      for analyses and we examined the data for heterogeneity (I2 statistic). We
      created a 'Summary of findings' table using GRADEpro. MAIN RESULTS: We included
      15 studies in the review, comprising a total of 1822 adult participants. There
      are 12 studies awaiting classification, and eight ongoing studies.None of the 15
      included studies considered the paediatric population. Four studies were
      conducted in the abdominal and orthopaedic surgery setting (lumbar spine, or knee
      and hip replacement), one study in the carotid endarterectomy setting, and the
      remaining 10 studies in the aortic or cardiac surgery setting. The main sources
      of bias in the included studies related to potential conflict of interest from
      industry sponsorship, unclear blinding status or missing participant data.Two
      studies with 312 participants considered postoperative neurological injury,
      however no pooled effect estimate could be calculated due to discordant direction
      of effect between studies (low-quality evidence). One study (N = 126) in
      participants undergoing major abdominal surgery reported that 4/66 participants
      experienced neurological injury with blinded monitoring versus 0/56 in the active
      monitoring group. A second study (N = 195) in participants having coronary artery
      bypass surgery reported that 1/96 participants experienced neurological injury in
      the blinded monitoring group compared with 4/94 participants in the active
      monitoring group.We are uncertain whether active cerebral NIRS monitoring has an
      important effect on the risk of postoperative stroke because of the low number of
      events and wide confidence interval (RR 0.25, 95% CI 0.03 to 2.20; 2 studies, 240
      participants; low-quality evidence).We are uncertain whether active cerebral NIRS
      monitoring has an important effect on postoperative delirium because of the wide
      confidence interval (RR 0.63, 95% CI 0.27 to 1.45; 1 study, 190 participants; low
      quality evidence).Two studies with 126 participants showed that active cerebral
      NIRS monitoring may reduce the incidence of mild postoperative cognitive
      dysfunction (POCD) as defined by the original studies at one week after surgery
      (RR 0.53, 95% CI 0.30 to 0.95, I2 = 49%, low-quality evidence).Based on six
      studies with 962 participants, there was moderate-quality evidence that active
      cerebral oxygenation monitoring probably does not decrease the occurrence of POCD
      (decline in cognitive function) at one week after surgery (RR 0.62, 95% CI 0.37
      to 1.04, I2 = 80%). The different type of monitoring equipment in one study could
      potentially be the cause of the heterogeneity.We are uncertain whether active
      cerebral NIRS monitoring has an important effect on intraoperative mortality or
      postoperative mortality because of the low number of events and wide confidence
      interval (RR 0.63, 95% CI 0.08 to 5.03, I2= 0%; 3 studies, 390 participants; low
      quality evidence). There was no evidence to determine whether routine use of NIRS
      based cerebral oxygenation monitoring causes adverse effects. AUTHORS'
      CONCLUSIONS: The effects of perioperative active cerebral NIRS monitoring of
      brain oxygenation in adults for reducing the occurrence of short-term, mild POCD
      are uncertain due to the low quality of the evidence. There is uncertainty as to
      whether active cerebral NIRS monitoring has an important effect on postoperative
      stroke, delirium or death because of the low number of events and wide confidence
      intervals. The conclusions of this review may change when the eight ongoing
      studies are published and the 12 studies awaiting assessment are classified. More
      RCTs performed in the paediatric population and high-risk patients undergoing non
      cardiac surgery (e.g. neurosurgery, carotid endarterectomy and other surgery) are
      needed.

PMID- 29341067
TI  - Vitamin E for antipsychotic-induced tardive dyskinesia.
AB  - BACKGROUND: Antipsychotic (neuroleptic) medication is used extensively to treat
      people with chronic mental illnesses. Its use, however, is associated with
      adverse effects, including movement disorders such as tardive dyskinesia (TD) - a
      problem often seen as repetitive involuntary movements around the mouth and face.
      Vitamin E has been proposed as a treatment to prevent or decrease TD. OBJECTIVES:
      The primary objective was to determine the clinical effects of vitamin E in
      people with schizophrenia or other chronic mental illness who had developed
      antipsychotic-induced TD.The secondary objectives were:1. to examine whether the
      effect of vitamin E was maintained as duration of follow-up increased;2. to test
      the hypothesis that the use of vitamin E is most effective for those with early
      onset TD (less than five years) 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 included reports if
      they were controlled trials dealing with people with antipsychotic-induced TD and
      schizophrenia who remained on their antipsychotic medication and had been
      randomly allocated to either vitamin E or to a placebo, no intervention, or any
      other intervention. DATA COLLECTION AND ANALYSIS: We independently extracted data
      from these trials and we estimated risk ratios (RR) or mean differences (MD),
      with 95% confidence intervals (CI). We assumed that people who left early had no
      improvement. We assessed risk of bias and created a 'Summary of findings' table
      using GRADE. MAIN RESULTS: The review now includes 13 poorly reported randomised
      trials (total 478 people), all participants were adults with chronic psychiatric
      disorders, mostly schizophrenia, and antipsychotic-induced TD. There was no clear
      difference between vitamin E and placebo for the outcome of TD: not improved to a
      clinically important extent (6 RCTs, N = 264, RR 0.95, 95% CI 0.89 to 1.01, low
      quality evidence). However, people allocated to placebo may show more
      deterioration of their symptoms compared with those given vitamin E (5 RCTs, N =
      85, RR 0.23, 95% CI 0.07 to 0.76, low-quality evidence). There was no evidence of
      a difference in the incidence of any adverse effects (9 RCTs, N = 205, RR 1.21,
      95% CI 0.35 to 4.15, very low-quality evidence), extrapyramidal adverse effects
      (1 RCT, N = 104, MD 1.10, 95% CI -1.02 to 3.22, very low-quality evidence), or
      acceptability of treatment (measured by participants leaving the study early)
      (medium term, 8 RCTs, N = 232, RR 1.07, 95% CI 0.64 to 1.80, very low-quality
      evidence). No trials reported on social confidence, social inclusion, social
      networks, or personalised quality of life, outcomes designated important to
      patients. There is no trial-based information regarding the effect of vitamin E
      for those with early onset of TD. AUTHORS' CONCLUSIONS: Small trials of limited
      quality suggest that vitamin E may protect against deterioration of TD. There is
      no evidence that vitamin E improves symptoms of this problematic and disfiguring
      condition once established. New and better trials are indicated in this under
      researched area, and, of the many adjunctive treatments that have been given for
      TD, vitamin E would be a good choice for further evaluation.

PMID- 29341068
TI  - Analysis of hypo- and hypermagnesemia in an intensive care unit cohort.
AB  - INTRODUCTION: The aim of this study was to evaluate if magnesium deviations
      correlate with higher 180 day overall mortality or increased morbidity, compared
      to controls. METHODS: We conducted a retrospective study on 5369 patients with
      22,003 magnesium values treated at the Adult Intensive Care Unit at Skane
      University Hospital, Lund, Sweden during 2006-2014. The patients were
      retrospectively divided into a control group with only normal magnesium values
      0.7-1.0 mmol/l, and three study groups; hypomagnesemic; Mg2+ < 0.7 mmol/l,
      hypermagnesemic; Mg2+ > 1.0 mmol/l and an unstable mixed group showing both
      hypo/hypermagnesemia. Gender, age, disease severity represented by maximum organ
      system SOFA score, renal SOFA score, lowest potassium value and diagnoses classes
      were included in a Cox hazard model in order to adjust for confounding factors,
      with time to death in the first 180 days from the ICU admission as outcome.
      RESULTS: The hypermagnesemic study group and the mixed group showed increased
      hazard ratios for mortality; 1.4 (CI 98.3% 1.2, 1.6, P < 0.0001) and 2.1 (CI
      98.3% 1.2, 2.8, P < 0.0001) respectively, compared to controls, while the
      hypomagnesemic group did not reach significance. In addition, patients in the
      hypermagnesemic and the mixed groups are older, more ill with significantly
      higher EMR and SOFA scores and show significantly longer ventilator times and ICU
      stays, compared to controls. CONCLUSIONS: Patients with magnesium deviations are
      more ill compared to patients with explicitly normal magnesium values throughout
      the ICU stay. Cox analysis suggests that the magnesium deviation itself might
      have an impact on mortality.

PMID- 29341069
TI  - Reliability and validity of the instrument for scoring clinical outcomes of
      research for epidermolysis bullosa (iscorEB).
AB  - BACKGROUND: Epidermolysis bullosa (EB) is a group of rare and currently incurable
      genetic blistering disorders. As more pathogenic-driven therapies are being
      developed, there is an important need for EB-specific validated outcomes measures
      designed for use in clinical trials. OBJECTIVES: To test the reliability and
      construct validity of an instrument for scoring clinical outcomes of research for
      EB (iscorEB), a new combined clinician- and patient-reported outcomes tool.
      METHODS: We conducted an observational study consisting of independent 1-day
      assessments (six assessors) at two academic hospitals. The assessments consisted
      of iscorEB clinician (iscorEB-c), Birmingham Epidermolysis Bullosa Severity
      (BEBS) and global severity assessment for physicians; and iscorEB patient
      (iscorEB-p), Quality of Life evaluation in Epidermolysis Bullosa and Children's
      Dermatology Life Quality Index for patients. Construct validity and intraclass
      correlation coefficients (ICCs) for interobserver, intraobserver and test-retest
      reliability were calculated. RESULTS: Overall, 31 patients with a mean age of
      19.5 years (1.8-45.2) were included. Disease severity was mild in 42% of cases,
      moderate in 29% and severe in 29%. The interobserver ICC was 0.96 for both the
      clinician-reported section of iscorEB-c and BEBS. The ICC for intraobserver
      reliability was 0.91 and 0.70 for the skin and mucosal domains of iscorEB-c,
      respectively. Cronbach's alpha for iscorEB-c was 0.89. The test-retest
      reliability of iscorEB-p was 0.97 and Cronbach's alpha was 0.84. The clinical
      score differentiated between subjects with mild, moderate and severe disease, and
      both clinical and patient subscores discriminated between recessive dystrophic EB
      and other EB subtypes. CONCLUSIONS: iscorEB has robust reliability and construct
      validity, including strong ability to distinguish EB types and severities.
      Further studies are planned to test its responsiveness to change.

PMID- 29341072
TI  - Epidermal melanocytes in segmental vitiligo show altered expression of E
      cadherin, but not P-cadherin.

PMID- 29341070
TI  - Personality Changes During the Transition from Cognitive Health to Mild Cognitive
      Impairment.
AB  - BACKGROUND/OBJECTIVES: Behavioral problems in individuals with Alzheimer's
      disease (AD) impose major management challenges. Current prevention strategies
      are anchored to cognitive outcomes, but behavioral outcomes may provide another,
      clinically relevant opportunity for preemptive therapy. We sought to determine
      whether personality changes that predispose to behavioral disorders arise during
      the transition from preclinical AD to mild cognitive impairment (MCI). DESIGN:
      Longitudinal observational cohort study. SETTING: Academic medical center.
      PARTICIPANTS: Members of an apolipoprotein E (APOE) E4 genetically enriched
      cohort of Maricopa County residents who were neuropsychiatrically healthy at
      entry (N = 277). Over a mean interval of 7 years, 25 who developed MCI and had
      the Neuroticism, Extraversion, and Openness Personality Inventory-Revised (NEO-PI
      R) before and during the MCI transition epoch were compared with 252
      nontransitioners also with serial NEO-PI-R administrations. INTERVENTION:
      Longitudinal administration of the NEO-PI-R and neuropsychological test battery.
      MEASUREMENTS: Change in NEO-PI-R factor scores (neuroticism, extraversion,
      openness, agreeableness, conscientiousness) from entry to the epoch of MCI
      diagnosis or an equivalent follow-up duration in nontransitioners. RESULTS: NEO
      PI-R neuroticism T-scores increased significantly more in MCI transitioners than
      in nontransitioners (mean 2.9, 95% confidence interval (CI) = 0.9-4.9 vs 0, 95%
      CI = -0.7-0.7, P = .02), and openness decreased more in MCI transitioners than in
      nontransitioners (-4.8, 95% CI = -7.3 to -2.4 vs -1.0, 95% CI = -1.6 to -0.4, P <
      .001). Concurrent subclinical but statistically significant changes in behavioral
      scores worsened more in MCI transitioners than nontransitioners for measures of
      depression, somatization, irritability, anxiety, and aggressive attitude.
      CONCLUSION: Personality and subclinical behavioral changes begin during the
      transition from preclinical AD to incident MCI and qualitatively resemble the
      clinically manifest behavioral disorders that subsequently arise in individuals
      with frank dementia.

PMID- 29341071
TI  - Anticholinergic medication for antipsychotic-induced tardive dyskinesia.
AB  - BACKGROUND: Antipsychotic (neuroleptic) medication is used extensively to treat
      people with serious mental illnesses. However, it is associated with a wide range
      of adverse effects, including movement disorders. Because of this, many people
      treated with antipsychotic medication also receive anticholinergic drugs in order
      to reduce some of the associated movement side-effects. However, there is also a
      suggestion from animal experiments that the chronic administration of
      anticholinergics could cause tardive dyskinesia. OBJECTIVES: To determine whether
      the use or the withdrawal of anticholinergic drugs (benzhexol, benztropine,
      biperiden, orphenadrine, procyclidine, scopolamine, or trihexylphenidyl) are
      clinically effective for the treatment of people with both antipsychotic-induced
      tardive dyskinesia and schizophrenia or other chronic mental illnesses. SEARCH
      METHODS: We retrieved 712 references from searching the Cochrane Schizophrenia
      Group's Study-Based Register of Trials including the registries of clinical
      trials (16 July 2015 and 26 April 2017). We also inspected references of all
      identified studies for further trials and contacted authors of trials for
      additional information. SELECTION CRITERIA: We included reports identified in the
      search if they were controlled trials dealing with people with antipsychotic
      induced tardive dyskinesia and schizophrenia or other chronic mental illness who
      had been randomly allocated to (a) anticholinergic medication versus placebo (or
      no intervention), (b) anticholinergic medication versus any other intervention
      for the treatment of tardive dyskinesia, or (c) withdrawal of anticholinergic
      medication versus continuation of anticholinergic medication. DATA COLLECTION AND
      ANALYSIS: We independently extracted data from included trials and we estimated
      risk ratios (RR) with 95% confidence intervals (CIs). We assumed that people who
      left early had no improvement. We assessed risk of bias and created a 'Summary of
      findings' table using GRADE. MAIN RESULTS: The previous version of this review
      included no trials. We identified two trials that could be included from the 2015
      and 2017 searches. They randomised 30 in- and outpatients with schizophrenia in
      the USA and Germany. 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 outcome data were not
      fully reported.Findings were sparse. One study reported on the primary outcomes
      and found that significantly more participants allocated to procyclidine
      (anticholinergic) had not improved to a clinically important extent compared with
      those allocated to isocarboxazid (MAO-inhibitor) after 40 weeks' treatment (1
      RCT, n = 20; RR 4.20, 95% CI 1.40 to 12.58; very low quality evidence); that
      there was no evidence of a difference in the incidence of any adverse effects (1
      RCT, n = 20; RR 0.33, 95% CI 0.02 to 7.32; very low quality evidence); or
      acceptability of treatment (measured by participants leaving the study early) (1
      RCT, n = 20; RR 0.33, 95% CI 0.02 to 7.32; very low quality evidence). The other
      trial compared anticholinergic withdrawal with anticholinergic continuation and
      found no evidence of a difference in the incidence of acceptability of treatment
      (measured by participants leaving the study early) (1 RCT, n = 10; RR 2.14, 95%
      CI 0.11 to 42.52; very low quality evidence).No trials reported on social
      confidence, social inclusion, social networks, or personalised quality of life -
      outcomes designated important to patients. No studies comparing either i.
      anticholinergics with placebo or no treatment, or ii. studies of anticholinergic
      withdrawal, were found that reported on the primary outcome 'no clinically
      important improvement in TD symptoms and adverse events'. AUTHORS' CONCLUSIONS:
      Based on currently available evidence, no confident statement can be made about
      the effectiveness of anticholinergics to treat people with antipsychotic-induced
      tardive dyskinesia. The same applies for the withdrawal of such medications.
      Whether the withdrawal of anticholinergics may benefit people with antipsychotic
      induced TD should be evaluated in a parallel-group, placebo-controlled randomised
      trial, with adequate sample size and at least 6 weeks of follow-up.

PMID- 29341073
TI  - Did You Know?

PMID- 29341074
TI  - Back to Basics: The Universal Protocol: 1.4 www.aornjournal.org/content/cme.

PMID- 29341075
TI  - Slate of Candidates and Voting Procedures.

PMID- 29341076
TI  - Guideline Quick View: Medication Safety.

PMID- 29341077
TI  - Assessing Use Errors Related to the Interface Design of Electrosurgical Units.
AB  - Medical device use errors, such as instrument connection errors made with
      electrosurgical units (ESUs), can lead to adverse events. Current device
      acquisition processes at health care facilities do not typically include a
      proactive evaluation of use-error risk before device purchase. We conducted an
      evaluation to identify ESU user interface design features that can help prevent
      or mitigate instrument connection errors during clinical care. Thirty-six current
      ESU users participated in the evaluation. We used a randomized crossover design
      in which each participant used two ESU models in a simulated OR scenario. We
      compared participants' instrument connection accuracy, efficiency, and subjective
      feedback regarding the user interface design across the two ESU models. Overall,
      we found that the ESU model that incorporated more user interface design
      principles resulted in better performance and increased acceptance from users.
      Based on the results, we designed a decision-support tool to assess the risk of
      instrument connection errors before ESU purchase.

PMID- 29341078
TI  - Bylaws Committee 2017-2018 Changes.

PMID- 29341079
TI  - Guideline for manual chemical high-level disinfection.

PMID- 29341080
TI  - Managing distractions to maintain focus on patients.

PMID- 29341081
TI  - Educational Opportunities.

PMID- 29341082
TI  - AORN Global Surgical Conference & Expo 2018 Exhibitors.

PMID- 29341084
TI  - AORN Nominating and Leadership Development Committee.

PMID- 29341083
TI  - Factors Contributing to Perioperative Medication Errors: A Systematic Literature
      Review: 2.1 www.aornjournal.org/content/cme.

PMID- 29341086
TI  - Clinical Issues-January 2018: 1.2 www.aornjournal.org/content/cme.

PMID- 29341087
TI  - July Syndrome.

PMID- 29341088
TI  - Evidence appraisal of Boonchan T, Wilasrusmee C, McEvoy M, Attia J, Thakkinstian
      A. Network meta-analysis of antibiotic prophylaxis for prevention of surgical
      site infection after groin hernia surgery. Br J Surg. 2017;104(2):e106-e117.
      doi:10.1002/bjs.10441.

PMID- 29341089
TI  - Candidate Biographical Information and Election Statements.

PMID- 29341090
TI  - Annual conference promises new learning opportunities.

PMID- 29341091
TI  - The Importance of Understanding Health Literacy for Perioperative Patient Safety.

PMID- 29341093
TI  - AORN Board of Directors.

PMID- 29341092
TI  - New Editor-in-Chief for the AORN Journal.

PMID- 29341095
TI  - AORN Global Surgical Conference & Expo 2018 Speaker Interviews.

PMID- 29341094
TI  - Implementing a Perioperative Nursing Student Summer Internship.
AB  - Using qualitative research and a collaborative academic service partnership, we
      created an innovative 120-hour perioperative nursing summer internship for eight
      undergraduate nursing students in 2016. Recognizing that perioperative exposure
      is limited in the traditional baccalaureate program, this unpaid internship
      served to clarify student perceptions of perioperative nursing care and encourage
      graduates to meet perioperative workforce demands. We based the theoretical and
      practical student learning experiences on the AORN Periop 101 learning modules
      and included faculty-led discussions, student journaling, and onsite precepted
      clinical activities. Evaluation data revealed that students achieved an enhanced
      awareness of perioperative nursing, and a majority of the participants expressed
      a desire to enter the perioperative field after graduation. We suggest that
      stakeholders continue to strategize ways to maximize educational preparation to
      address the evolving health care market supply and demand.

PMID- 29341097
TI  - A Postprocedure Wrap-up Tool for Improving OR Communication and Performance.
AB  - In 2015, perioperative nursing staff members at a community hospital designed and
      implemented a tool to help improve communication and performance. Our
      postprocedure wrap-up tool and its follow-up process have allowed us to achieve
      improvements in both efficiency and staff member satisfaction. By implementing a
      process to document problems as they occur and quickly transmit information to
      the staff members who are best able to correct these issues, we greatly improved
      our workflow. Furthermore, by inputting information into spreadsheets using
      problem codes, thereby replacing anecdotal information with hard data, we
      targeted areas that needed improvement and used that information for budget
      planning, training, and allocating resources. Enlisting the input of all members
      of the surgical team allowed us to identify the root causes of issues that
      interfered with the staff members' ability to provide efficient, safe, and
      reliable patient care.

PMID- 29341098
TI  - Embrace Action: Make Personal and Professional Resolutions.

PMID- 29341099
TI  - Ventriculoperitoneal shunt.

PMID- 29341100
TI  - Underdiagnosis of Influenza Virus Infection in Hospitalized Older Adults.
AB  - OBJECTIVES: To describe factors associated with provider-ordered influenza
      testing in hospitalized older adults. DESIGN: Information on participant
      demographics, symptoms, and provider-ordered influenza testing were collected by
      questionnaire and chart review. We conducted prospective laboratory-based
      surveillance using reverse-transcriptase polymerase chain reaction (RT-PCR), the
      criterion standard for diagnosis of influenza, to determine how participant
      characteristics and provider-ordered testing affected accurate influenza
      diagnosis. SETTING: One academic and three community hospitals in Davidson
      County, Tennessee. PARTICIPANTS: Adults aged 18 and older with acute respiratory
      illness or nonlocalizing fever (N=1,422). MEASUREMENTS: We compared
      characteristics of participants with and without provider-ordered testing for
      influenza using the Wilcoxon test and Pearson chi-square test. Multivariable
      logistic regression models were used to identify factors predictive of provider
      ordered influenza testing. RESULTS: Twenty-eight percent (399/1,422) of
      participants had provider-ordered influenza testing. Participants who were tested
      were younger than those not tested (58 +/- 18 vs 66 +/- 15, p<.001) and more
      likely to have influenza-like illness (ILI) (71% vs 49%, p<.001). ILI decreased
      with increasing age (aged 18-49, 63%; aged 50-64, 60%; aged >=65, 48%). ILI and
      younger age were independent predictors of provider-ordered testing. Of the 136
      participants with influenza confirmed using RT-PCR, ILI was the only significant
      predictor of provider-ordered testing (adjusted odds ratio=3.43, 95% confidence
      interval=1.22-9.70). CONCLUSION: Adults aged 65 and older hospitalized with fever
      or respiratory symptoms during influenza season are less likely to undergo a
      provider-ordered influenza test than younger adults. Some, but not all, of this
      disparity is due to a lower likelihood of ILI. Further strategies are needed to
      increase clinician awareness and testing in this vulnerable group.

PMID- 29341101
TI  - An overview of confounding. Part 2: how to identify it and special situations.
AB  - Confounding biases study results when the effect of the exposure on the outcome
      mixes with the effects of other risk and protective factors for the outcome that
      are present differentially by exposure status. However, not all differences
      between the exposed and unexposed group cause confounding. Thus, sources of
      confounding must be identified before they can be addressed. Confounding is
      absent in an ideal study where all of the population of interest is exposed in
      one universe and is unexposed in a parallel universe. In an actual study, an
      observed unexposed population represents the unobserved parallel universe.
      Thinking about differences between this substitute population and the unexposed
      parallel universe helps identify sources of confounding. These differences can
      then be represented in a diagram that shows how risk and protective factors for
      the outcome are related to the exposure. Sources of confounding identified in the
      diagram should be addressed analytically and through study design. However,
      treating all factors that differ by exposure status as confounders without
      considering the structure of their relation to the exposure can introduce bias.
      For example, conditions affected by the exposure are not confounders. There are
      also special types of confounding, such as time-varying confounding and unfixable
      confounding. It is important to evaluate carefully whether factors of interest
      contribute to confounding because bias can be introduced both by ignoring
      potential confounders and by adjusting for factors that are not confounders. The
      resulting bias can result in misleading conclusions about the effect of the
      exposure of interest on the outcome.

PMID- 29341102
TI  - Fungal kerion of the vulva.

PMID- 29341103
TI  - An overview of confounding. Part 1: the concept and how to address it.
AB  - Confounding is an important source of bias, but it is often misunderstood. We
      consider how confounding occurs and how to address confounding using examples.
      Study results are confounded when the effect of the exposure on the outcome,
      mixes with the effects of other risk and protective factors for the outcome. This
      problem arises when these factors are present to different degrees among the
      exposed and unexposed study participants, but not all differences between the
      groups result in confounding. Thinking about an ideal study where all of the
      population of interest is exposed in one universe and is unexposed in a parallel
      universe helps to distinguish confounders from other differences. In an actual
      study, an observed unexposed population is chosen to stand in for the unobserved
      parallel universe. Differences between this substitute population and the
      parallel universe result in confounding. Confounding by identified factors can be
      addressed analytically and through study design, but only randomization has the
      potential to address confounding by unmeasured factors. Nevertheless, a given
      randomized study may still be confounded. Confounded study results can lead to
      incorrect conclusions about the effect of the exposure of interest on the
      outcome.

PMID- 29341104
TI  - Hair cortisol is elevated in patients with erythropoietic protoporphyria and
      correlates with body mass index and quality of life.

PMID- 29341105
TI  - Metabolomic characterization of human hippocampus from drug-resistant epilepsy
      with mesial temporal seizure.
AB  - OBJECTIVE: Within a complex systems biology perspective, we wished to assess
      whether hippocampi with established neuropathological features have distinct
      metabolome. Apparently normal hippocampi with no signs of sclerosis (noHS), were
      compared to hippocampal sclerosis (HS) type 1 (HS1) and/or type 2 (HS2).
      Hippocampus metabolome from patients with epilepsy-associated neuroepithelial
      tumors (EANTs), namely, gangliogliomas (GGs) and dysembryoplastic neuroepithelial
      tumors (DNTs), was also compared to noHS epileptiform tissue. METHODS: All
      patients underwent standardized temporal lobectomy. We applied 1 H high
      resolution magic angle spinning nuclear magnetic resonance (HRMAS NMR)
      spectroscopy to 48 resected human hippocampi. NMR spectra allowed quantification
      of 21 metabolites. Data were analyzed using multivariate analysis based on mutual
      information. RESULTS: Clear distinct metabolomic profiles were observed between
      all studied groups. Sixteen and 18 expected metabolite levels out of 21 were
      significantly different for HS1 and HS2, respectively, when compared to noHS.
      Distinct concentration variations for glutamine, glutamate, and N-acetylaspartate
      (NAA) were observed between HS1 and HS2. Hippocampi from GG and DNT patients
      showed 7 and 11 significant differences in metabolite concentrations when
      compared to the same group, respectively. GG and DNT had a clear distinct
      metabolomic profile, notably regarding choline compounds, glutamine, glutamate,
      aspartate, and taurine. Lactate and acetate underwent similar variations in both
      groups. SIGNIFICANCE: HRMAS NMR metabolomic analysis was able to disentangle
      metabolic profiles between HS, noHS, and epileptic hippocampi associated with
      EANT. HRMAS NMR metabolomic analysis may contribute to a better identification of
      abnormal biochemical processes and neuropathogenic combinations underlying mesial
      temporal lobe epilepsy.

PMID- 29341106
TI  - The effect of surgery on subsequent pregnancy outcomes among patients with
      cesarean scar diverticulum.
AB  - OBJECTIVE: To determine whether surgical treatment of cesarean scar diverticulum
      (CSD) reduced adverse outcomes during the subsequent pregnancy. METHODS: A
      retrospective observational study was conducted using the medical records of
      pregnant women with CSD who attended a single hospital in Hangzhou, China,
      between January 1, 2014, and December 31, 2016. Baseline characteristics and
      pregnancy outcomes were compared between the surgery group and the no surgery
      group. RESULTS: There were 106 patients included in the study, 83 in the surgery
      group and 23 in the no surgery group. The CSD size was greater in all dimensions
      for the surgery group versus the no surgery group: length (P<0.001), width
      (P=0.001), and depth (P=0.030). The remaining myometrium was thinner among women
      in the surgery group than those in the no surgery group (P=0.011). In all, 76
      (91.6%) women in the surgery group were symptomatic. The incidence of live
      delivery pregnancy was higher (P=0.033) and the incidence of cesarean scar
      pregnancy was lower (P=0.019) in the surgery group versus the no surgery group.
      Surgery increased the thickness of the lower uterine segment (P<0.001); however,
      it did not reduce the risks of placenta previa or placenta accreta (P=0.683) and
      uterine dehiscence or uterine rupture (P=0.458). CONCLUSION: Surgical
      intervention reduced the incidence of cesarean scar pregnancy and increased the
      number of live deliveries.

PMID- 29341107
TI  - Anthropogenic nitrogen deposition ameliorates the decline in tree growth caused
      by a drier climate.
AB  - Most forest ecosystems are simultaneously affected by concurrent global change
      drivers. However, when assessing these effects, studies have mainly focused on
      the responses to single factors and have rarely evaluated the joined effects of
      the multiple aspects of environmental change. Here, we analyzed the combined
      effects of anthropogenic nitrogen (N) deposition and climatic conditions on the
      radial growth of Acer saccharum, a dominant tree species in eastern North
      American forests. We capitalized on a long-term N deposition study, replicated
      along a latitudinal gradient, that has been taking place for more than 20 yr. We
      analyzed tree radial growth as a function of anthropogenic N deposition (ambient
      and experimental addition) and of summer temperature and soil water conditions.
      Our results reveal that experimental N deposition enhances radial growth of this
      species, an effect that was accentuated as temperature increased and soil water
      became more limiting. The spatial and temporal extent of our data also allowed us
      to assert that the positive effects of growing under the experimental N
      deposition are likely due to changes in the physiological performance of this
      species, and not due to the positive correlation between soil N and soil water
      holding capacity, as has been previously speculated in other studies. Our
      simulations of tree growth under forecasted climate scenarios specific for this
      region also revealed that although anthropogenic N deposition may enhance tree
      growth under a large array of environmental conditions, it will not mitigate the
      expected effects of growing under the considerably drier conditions
      characteristic of our most extreme climatic scenario.

PMID- 29341108
TI  - Characteristics of tendon derived stem cells according to different factors to
      induce the tendinopathy.
AB  - Tendon derived stem cells (TDSCs) have been used as a therapeutic agent and as a
      healing marker. However, there has been no study about the characteristics of
      TDSCs extracted from tendinopathic tendon tissues. The aim of this study was to
      find the different characteristics of TDSCs according to the factors to induce
      the tendinopathy. Five- and fifteen-week old Sprague Dawley rats were used for
      this study and chemically-induced and injury-induced tendinopathy models were
      made depending on the age of the animal for different types of tendinopathy.
      TDSCs from chemically-induced tendinopathy showed markedly low proliferation
      compared to those from age-matched normal control and injury-induced
      tendinopathy. In addition, TDSCs from chemically-induced tendinopathy progressed
      to osteogenesis under an osteogenic differentiation environment more than those
      from other groups. In contrast, TDSCs from injury-induced tendinopathy showed
      markedly high proliferation and high expression of type III collagen and alpha
      SMA compared to other groups. Adipogenic potentials in TDSCs from injury-induced
      tendinopathy were also higher. These different characteristics might be helpful
      in the development new therapeutic agents for tendon regeneration according to
      different factors to induce the tendinopathy.

PMID- 29341109
TI  - The prescribable drugs with efficacy in experimental epilepsies (PDE3) database
      for drug repurposing research in epilepsy.
AB  - OBJECTIVE: Current antiepileptic drugs (AEDs) have several shortcomings. For
      example, they fail to control seizures in 30% of patients. Hence, there is a need
      to identify new AEDs. Drug repurposing is the discovery of new indications for
      approved drugs. This drug "recycling" offers the potential of significant savings
      in the time and cost of drug development. Many drugs licensed for other
      indications exhibit antiepileptic efficacy in animal models. Our aim was to
      create a database of "prescribable" drugs, approved for other conditions, with
      published evidence of efficacy in animal models of epilepsy, and to collate data
      that would assist in choosing the most promising candidates for drug repurposing.
      METHODS: The database was created by the following: (1) computational literature
      mining using novel software that identifies Medline abstracts containing the name
      of a prescribable drug, a rodent model of epilepsy, and a phrase indicating
      seizure reduction; then (2) crowdsourced manual curation of the identified
      abstracts. RESULTS: The final database includes 173 drugs and 500 abstracts. It
      is made freely available at www.liverpool.ac.uk/D3RE/PDE3. The database is
      reliable: 94% of the included drugs have corroborative evidence of efficacy in
      animal models (for example, evidence from multiple independent studies). The
      database includes many drugs that are appealing candidates for repurposing, as
      they are widely accepted by prescribers and patients-the database includes half
      of the 20 most commonly prescribed drugs in England-and they target many proteins
      involved in epilepsy but not targeted by current AEDs. It is important to note
      that the drugs are of potential relevance to human epilepsy-the database is
      highly enriched with drugs that target proteins of known causal human epilepsy
      genes (Fisher's exact test P-value < 3 * 10-5 ). We present data to help
      prioritize the most promising candidates for repurposing from the database.
      SIGNIFICANCE: The PDE3 database is an important new resource for drug repurposing
      research in epilepsy.

PMID- 29341110
TI  - Eurogin roadmap 2017: Triage strategies for the management of HPV-positive women
      in cervical screening programs.
AB  - Cervical cancer screening will rely, increasingly, on HPV testing as a primary
      screen. The requirement for triage tests which can delineate clinically
      significant infection is thus prescient. In this EUROGIN 2017 roadmap,
      justification behind the most evidenced triages is outlined, as are challenges
      for implementation. Cytology is the triage with the most follow-up data; the
      existence of an HR-HPV-positive, cytology-negative group presents a challenge and
      retesting intervals for this group (and choice of retest) require careful
      consideration. Furthermore, cytology relies on subjective skills and while
      adjunctive dual-staining with p16/Ki67 can mitigate inter-operator/-site
      disparities, clinician-taken samples are required. Comparatively, genotyping and
      methylation markers are objective and are applicable to self-taken samples,
      offering logistical advantages including in low and middle income settings.
      However, genotyping may have diminishing returns in immunised populations and
      type(s) included must balance absolute risk for disease to avoid low specificity.
      While viral and cellular methylation markers show promise, more prospective data
      are needed in addition to refinements in automation. Looking forward, systems
      that detect multiple targets concurrently such as next generation sequencing
      platforms will inform the development of triage tools. Additionally, multistep
      triage strategies may be beneficial provided they do not create complex,
      unmanageable pathways. Inevitably, the balance of risk to cost(s) will be key in
      decision making, although defining an acceptable risk will likely differ between
      settings. Finally, given the significant changes to cervical screening and the
      variety of triage strategies, appropriate education of both health care providers
      and the public is essential.

PMID- 29341111
TI  - Variation and drivers of airflow patterns associated with olfactory concealment
      and habitat selection.
AB  - Many terrestrial predators rely on olfaction to detect prey; therefore, prey
      should select habitat to reduce detectability of their odor cues. One way prey
      can potentially conceal their odor is by selecting locations with high turbulence
      and/or updrafts, conditions that disperse odor plumes and make odor sources
      difficult to locate. However, it is unclear how these conditions vary among
      vegetation cover types and which vegetative features drive them. We assessed
      variation and drivers of variables hypothesized to influence olfactory
      concealment (turbulence intensity and airflow slope) and experimentally evaluated
      whether these variables indeed influence predator detection of simulated prey.
      Specifically, we compared vegetation patch-scale values of turbulence intensity
      and airflow slope among grassland, shrubland, and forest and assessed
      relationships among these airflow variables and local-scale vegetative features
      within each vegetation type. Additionally, we experimentally investigated the
      importance of turbulence intensity, airflow slope, and visual concealment for
      predicting predator detection of scented quail eggs. In all vegetation types, we
      documented high variability in airflow conditions. At the patch scale, turbulence
      intensity was greater in shrubland and grassland than in forest, and updrafts
      were most common in shrubland whereas downdrafts were most common in grassland.
      Grassland was the only vegetation type with strong relationships among turbulence
      intensity and local vegetation features; both visual concealment and vegetation
      height were positively related to turbulence intensity. Additionally, persistence
      of scented quail eggs in grassland was best predicted by turbulence intensity;
      egg persistence increased with turbulence intensity. Our characterization of
      differences in olfactory variables among vegetation types provides an important
      step towards building a clearer understanding of olfactory landscapes. Further,
      our observation of both patch- and local-scale variation in olfactory variables
      suggests that prey can potentially select for olfactory concealment at multiple
      scales. We hypothesize that olfactory concealment provided by high levels of
      turbulence intensity is an important component of cover in grassland, and that in
      grassland/shrubland landscapes, prey selection of shrubland patches reduces odor
      detectability. Our finding of a positive relationship between turbulence
      intensity and visual concealment also suggests that olfactory concealment may be
      a previously underappreciated confounding factor in studies of habitat selection.

PMID- 29341112
TI  - Conditionally reprogrammed cells (CRC) methodology does not allow the in vitro
      expansion of patient-derived primary and metastatic lung cancer cells.
AB  - Availability of tumor and non-tumor patient-derived models would promote the
      development of more effective therapeutics for non-small cell lung cancer
      (NSCLC). Recently, conditionally reprogrammed cells (CRC) methodology
      demonstrated exceptional potential for the expansion of epithelial cells from
      patient tissues. However, the possibility to expand patient-derived lung cancer
      cells using CRC protocols is controversial. Here, we used CRC approach to expand
      cells from non-tumoral and tumor biopsies of patients with primary or metastatic
      NSCLC as well as pulmonary metastases of colorectal or breast cancers. CRC
      cultures were obtained from both tumor and non-malignant tissues with
      extraordinary high efficiency. Tumor cells were tracked in vitro through
      tumorigenicity assay, monitoring of tumor-specific genetic alterations and marker
      expression. Cultures were composed of EpCAM+ lung epithelial cells lacking
      tumorigenic potential. NSCLC biopsies-derived cultures rapidly lost patient
      specific genetic mutations or tumor antigens. Similarly, pulmonary metastases of
      colon or breast cancer generated CRC cultures of lung epithelial cells. All CRC
      cultures examined displayed epithelial lung stem cell phenotype and function. In
      contrast, brain metastatic lung cancer biopsies failed to generate CRC cultures.
      In conclusion, patient-derived primary and metastatic lung cancer cells were
      negatively selected under CRC conditions, limiting the expansion to non-malignant
      lung epithelial stem cells from either tumor or non-tumor tissue sources. Thus,
      CRC approach cannot be applied for direct therapeutic testing of patient lung
      tumor cells, as the tumor-derived CRC cultures are composed of (non-tumoral)
      airway basal cells.

PMID- 29341113
TI  - Prospective emotion enables episodic prospection to shift time preference.
AB  - The episodic effect suggests that episodic prospection (imagining future events)
      can effectively reduce time discounting, the propensity to discount the value of
      delayed rewards relative to immediate ones. However, less clear is how episodic
      prospection modulates time preference. As engagement in episodic prospection
      usually evokes prospective emotions, it was proposed that episodic prospection
      might work by inducing prospective emotions. Although one previous study has
      attempted to provide evidence to the emotional account of the episodic effect,
      shortcomings in its experimental design make its conclusion questionable. In this
      study, we replicated previous experimental design with improvements to further
      test the effects of prospective emotion on time preference. By manipulating the
      emotional valency associated with episodic prospection in a delay discounting
      task, we found that positive episodic prospection attenuated time discounting;
      negative episodic prospection exacerbated time discounting; and episodic
      prospection did not shift time preference when prospective emotion is removed.
      These results were essentially identical to the result of the previous study.
      Together, these studies suggested that the effects of episodic prospection
      depended on prospective emotion. Thus, one cannot ignore prospective emotion if
      counting on episodic prospection to combat humans' impulsive behaviours.

PMID- 29341114
TI  - Recombinant human hepatocyte growth factor provides protective effects in
      cerulein-induced acute pancreatitis in mice.
AB  - Acute pancreatitis is a multifactorial disease associated with profound changes
      of the pancreas induced by release of digestive enzymes that lead to increase in
      proinflammatory cytokine production, excessive tissue necrosis, edema, and
      bleeding. Elevated levels of hepatocyte growth factor (HGF) and its receptor c
      Met have been observed in different chronic and acute pancreatic diseases
      including experimental models of acute pancreatitis. In the present study, we
      investigated the protective effects induced by the recombinant human HGF in a
      mouse model of cerulein-induced acute pancreatitis. Pancreatitis was induced by 8
      hourly administrations of supramaximal cerulein injections (50 ug/kg, ip). HGF
      treatment (20 ug/kg, iv), significantly attenuated lipase content and amylase
      activity in serum as well as the degree inflammation and edema overall leading to
      less severe histologic changes such as necrosis, induced by cerulein. Protective
      effects of HGF were associated with activation of pro-survival pathways such as
      Akt, Erk1/2, and Nrf2 and increase in executor survival-related proteins and
      decrease in pro-apoptotic proteins. In addition, ROS content and lipid
      peroxidation were diminished, and glutathione synthesis increased in pancreas.
      Systemic protection was observed by lung histology. In conclusion, our data
      indicate that HGF exerts an Nrf2 and glutathione-mediated protective effect on
      acute pancreatitis reflected by a reduction in inflammation, edema, and oxidative
      stress.

PMID- 29341115
TI  - Non-volant mammals from the Upper Parana River Basin: a data set from a critical
      region for conservation in Brazil.
AB  - The data set represents the first attempt at a large-scale inventory of non
      volant mammals, with potential applications to performing macroecological
      studies, developing conservation strategies, and undertaking population and
      community ecology research, but also to evaluate the ecological consequences of
      fragmentation and defaunation. Our objectives for compiling these data were to
      summarize information about inventories of non-volant mammals in the critically
      important area of the Upper Parana River Basin by focusing on species richness
      and index of frequency of occurrence and to identify gaps in knowledge regarding
      non-volant mammal communities in order to guide future sampling efforts. The data
      set comprises studies on communities of non-volant mammals from 52 locations
      covering more than 1,000 km2 and comprises portion of four Brazilian states in
      the Upper Parana River Basin. We listed 81 species of non-volant mammals
      distributed among 58 genera, 22 families, and 9 orders. Rodentia (28 species) was
      the richest order, followed by Carnivora (17 spp.) and Didelphimorphia (15 spp.).
      The richest family was Cricetidae (20 spp.), followed by Didelphidae (15 spp.),
      and Dasypodidae and Felidae (six spp.). Considering national conservation status,
      one species are considered endangered and 16 vulnerable. Considering global
      conservation status, 7 species are considered vulnerable, 10 are considered near
      threatened, and 6 are data deficient. According to the index of frequency of
      occurrence, Myrmecophaga tridactyla was the most frequent species, occurring at
      88.64% of all sites, while 25 species were considered very restricted, occurring
      in just 2.56% of all sites. In general, the non-volant mammal fauna was composed
      of mainly very restricted (VR, 25 species) and localized species (L, 25 species),
      which account for 61.7% of the known species, while 38.3% are restricted (R, 8
      species), common (C, 16 species), and widespread (W, 7 species). Seven marsupials
      and five small rodents had their distributions extended in the central-south of
      Brazil. All of these species are considered data deficient or threatened, which
      highlights the importance of these records. No copyright restrictions are
      associated with the use of this data set. Please cite this data paper when the
      data are used in publications. We also request that researchers and teachers
      inform us of how they are using the data.

PMID- 29341116
TI  - Rare missense mutations in RECQL and POLG associate with inherited predisposition
      to breast cancer.
AB  - Several known breast cancer susceptibility genes with moderate-to-high risk
      alleles encode proteins involved in DNA damage response (DDR). As these explain
      less than half of the hereditary breast cancer cases, additional predisposing
      alleles are likely to be discovered. Many of the previous studies utilizing
      massive parallel sequencing have focused on the protein-truncating variants, and
      the role of rare missense mutations has remained poorly addressed. To identify
      novel susceptibility factors, we have systematically analyzed the data from our
      parallel sequencing of 796 DDR genes in 189 Northern Finnish hereditary breast
      cancer patients for rare missense variants, predicted as deleterious. Thirty-five
      variants were studied here for the disease association using Finnish breast
      cancer case (n = 492-2,035) and control (n = 277-1,539) cohorts. As a result, two
      missense variants in genes involved in DNA replication, RECQL p.I156M and POLG
      p.L392V, the former involving genomic and the latter mitochondrial DNA
      replication, showed significant association with risk of breast cancer. Rare
      RECQL p.I156M allele was observed in breast cancer cases only (6/1,946, 0.3%, p =
      0.043), whereas POLG p.L392V was two times more frequent in breast cancer cases
      (53/2,238, 2.4%) compared to controls (18/1,539, 1.2%, OR = 2.1, 95% CI 1.2-3.5,
      p = 0.010). Based on the current genetic data, both RECQL p.I156M and POLG
      p.L392V represent novel breast cancer predisposing alleles.

PMID- 29341117
TI  - HOXD-AS1/miR-130a sponge regulates glioma development by targeting E2F8.
AB  - Glioma development is an extremely complex process with changes occurring in
      numerous genes. HOXD antisense growth-associated long noncoding RNA (HOXD-AS1),
      an important long noncoding RNA (lncRNA), is known to regulate metastasis-related
      gene expression in bladder cancer, ovarian cancer and neuroblastoma. Here, we
      elucidated the function and possible molecular mechanisms of lncRNA HOXD-AS1 in
      human glioma cells. Our results proved that HOXD-AS1 expression was upregulated
      in glioma tissues and in glioma cell lines. HOXD-AS1 overexpression promoted cell
      migration and invasion in vitro, whereas knockdown of HOXD-AS1 expression
      repressed these cellular processes. Mechanistic studies further revealed that
      HOXD-AS1 could compete with the transcription factor E2F8 to bind with miR-130a,
      thus affecting E2F8 expression. Additionally, reciprocal repression was observed
      between HOXD-AS1 and miR-130a, and miR-130a mediated the tumor-suppressive
      effects of HOXD-AS1 knockdown. Taken together, these results provide a
      comprehensive analysis of the role of HOXD-AS1 in glioma cells and offer
      important clues to understand the key roles of competing endogenous RNA (ceRNA)
      mechanisms in human glioma.

PMID- 29341119
TI  - Time to Settle the Fracking Controversy.

PMID- 29341120
TI  - Trajectories of Infants' Biobehavioral Development: Timing and Rate of A-Not-B
      Performance Gains and EEG Maturation.
AB  - This study examined how timing (i.e., relative maturity) and rate (i.e., how
      quickly infants attain proficiency) of A-not-B performance were related to
      changes in brain activity from age 6 to 12 months. A-not-B performance and
      resting EEG (electroencephalography) were measured monthly from age 6 to 12
      months in 28 infants and were modeled using logistic and linear growth curve
      models. Infants with faster performance rates reached performance milestones
      earlier. Infants with faster rates of increase in A-not-B performance had lower
      occipital power at 6 months and greater linear increases in occipital power. The
      results underscore the importance of considering nonlinear change processes for
      studying infants' cognitive development as well as how these changes are related
      to trajectories of EEG power.

PMID- 29341118
TI  - Inhibition of the Fibrinogen-Like Protein 2:FcgammaRIIB/RIII immunosuppressive
      pathway enhances antiviral T-cell and B-cell responses leading to clearance of
      lymphocytic choriomeningitis virus clone 13.
AB  - Persistent viruses evade immune detection by interfering with virus-specific
      innate and adaptive antiviral immune responses. Fibrinogen-like protein-2 (FGL2)
      is a potent effector molecule of CD4+  CD25+  FoxP3+ regulatory T cells and
      exerts its immunosuppressive activity following ligation to its cognate receptor,
      FcgammaRIIB/RIII. The role of FGL2 in the pathogenesis of chronic viral infection
      caused by lymphocytic choriomeningitis virus clone-13 (LCMV cl-13) was assessed
      in this study. Chronically infected fgl2+/+ mice had increased plasma levels of
      FGL2, with reduced expression of the maturation markers, CD80, CD86 and MHC-II on
      macrophages and dendritic cells and impaired production of neutralizing antibody.
      In contrast, fgl2-/- mice or fgl2+/+ mice that had been pre-treated with
      antibodies to FGL2 and FcgammaRIIB/RIII and then infected with LCMV cl-13
      developed a robust CD4+ and CD8+ antiviral T-cell response, produced high titred
      neutralizing antibody to LCMV and cleared LCMV. Treatment of mice with
      established chronic infection with antibodies to FGL2 and FcgammaRIIB/RIII was
      shown to rescue the number and functionality of virus-specific CD4+ and CD8+ T
      cells with reduced total and virus-specific T-cell expression of programmed cell
      death protein 1 leading to viral clearance. These results demonstrate an
      important role for FGL2 in viral immune evasion and provide a rationale to target
      FGL2 to treat patients with chronic viral infection.

PMID- 29341121
TI  - Violence, Guns, and Suicide in New Orleans: Results from a Qualitative Study of
      Recent Suicide Decedents.
AB  - Many Americans own guns to protect themselves against other people, but there is
      evidence that both victimization and gun access increase suicide risk. We
      conducted qualitative interviews with informants of 17 suicide cases in New
      Orleans of the 60 who died between January 2015 and April 2016 to understand the
      relationship between past trauma, gun access and storage, and suicide. Nine cases
      had experienced a past trauma, including three who had recently had a family
      member killed by homicide. Eight died via firearm; of those, seven owned the guns
      they used to take their lives and stored them locked (but loaded) at home or in
      their cars. Preventing community violence and addressing its sequelae may be
      important for reducing suicides. A multi-pronged strategy consisting of policies,
      education, and marketing will likely be needed to address the risk of suicide
      conferred by gun access.

PMID- 29341123
TI  - Do longer root hairs improve phosphorus uptake? Testing the hypothesis with
      transgenic Brachypodium distachyon lines overexpressing endogenous RSL genes.
AB  - Mutants without root hairs show reduced inorganic orthophosphate (Pi) uptake and
      compromised growth on soils when Pi availability is restricted. What is less
      clear is whether root hairs that are longer than wild-type provide an additional
      benefit to phosphorus (P) nutrition. This was tested using transgenic
      Brachypodium lines with longer root hairs. The lines were transformed with the
      endogenous BdRSL2 and BdRSL3 genes using either a constitutive promoter or a root
      hair-specific promoter. Plants were grown for 32 d in soil amended with various
      Pi concentrations. Plant biomass and P uptake were measured and genotypes were
      compared on the basis of critical Pi values and P uptake per unit root length.
      Ectopic expression of RSL2 and RSL3 increased root hair length three-fold but
      decreased plant biomass. Constitutive expression of BdRSL2, but not expression of
      BdRSL3, consistently improved P nutrition as measured by lowering the critical Pi
      values and increasing Pi uptake per unit root length. Increasing root hair length
      through breeding or biotechnology can improve P uptake efficiency if the
      pleotropic effects on plant biomass are avoided. Long root hairs, alone, appear
      to be insufficient to improve Pi uptake and need to be combined with other traits
      to benefit P nutrition.

PMID- 29341122
TI  - Impacts of Methane on Carbon Dioxide Storage in Brine Formations.
AB  - In the context of geological carbon sequestration (GCS), carbon dioxide (CO2 ) is
      often injected into deep formations saturated with a brine that may contain
      dissolved light hydrocarbons, such as methane (CH4 ). In this multicomponent
      multiphase displacement process, CO2 competes with CH4 in terms of dissolution,
      and CH4 tends to exsolve from the aqueous into a gaseous phase. Because CH4 has a
      lower viscosity than injected CO2 , CH4 is swept up into a 'bank' of CH4 -rich
      gas ahead of the CO2 displacement front. On the one hand, this may provide a
      useful tracer signal of an approaching CO2 front. On the other hand, the
      emergence of gaseous CH4 is undesirable because it poses a leakage risk of a far
      more potent greenhouse gas than CO2 if the cap rock is compromised. Open
      fractures or faults and wells could result in CH4 contamination of overlying
      groundwater aquifers as well as surface emissions. We investigate this process
      through detailed numerical simulations for a large-scale GCS pilot project (near
      Cranfield, Mississippi) for which a rich set of field data is available. An
      accurate cubic-plus-association equation-of-state is used to describe the non
      linear phase behavior of multiphase brine-CH4 -CO2 mixtures, and breakthrough
      curves in two observation wells are used to constrain transport processes. Both
      field data and simulations indeed show the development of an extensive plume of
      CH4 -rich (up to 90 mol%) gas as a consequence of CO2 injection, with important
      implications for the risk assessment of future GCS projects.

PMID- 29341124
TI  - Metric Assessment of the Pubic Bone Using Known and Novel Data Points for Sex
      Estimation.
AB  - Biological sex estimation of skeletal remains is essential in forensic and
      archaeological analyses. Anthropologists most often use the pelvis, which is the
      most sexually dimorphic element both morphologically and metrically. While
      nonmetric pubic bone features have been studied extensively, few metric studies
      have examined this individual bone for dimorphism. For this study, three
      observers examined three previously identified and ten novel measurements of the
      pubic body on a modern sample of isolated pubic bones from the Maricopa County
      Forensic Science Center (FSC), in Phoenix, Arizona (n = 400). A relationship
      between pubic body measurements and biological sex was demonstrated, with
      significant correlations. Discriminant function analyses found that five
      measurements, four of which were novel, discriminated between males (89%) and
      females (86%). Observer experience level did not significantly impact the
      results. These five measurements were reliable and show promise for inclusion in
      metric methods for assessment of sex.

PMID- 29341125
TI  - Gut microbiota and probiotics: novel immune system modulators in myasthenia
      gravis?
AB  - Gut microorganisms (microbiota) live in symbiosis with the host and influence
      human nutrition, metabolism, physiology, and immune development and function. The
      microbiota prevents pathogen infection to the host, and in turn the host provides
      a niche for survival. The alteration of gut bacteria composition (dysbiosis)
      could contribute to the development of immune-mediated diseases by influencing
      the immune system activation and driving the pro- and anti-inflammatory responses
      in order to promote or counteract immune reactions. Probiotics are nonpathogenic
      microorganisms able to interact with the gut microbiota and provide health
      benefits; their use has recently been exploited to dampen immunological response
      in several experimental models of autoimmune diseases. Here, we focus on the
      relationships among commensal bacteria, probiotics, and the gut, describing the
      main interactions occurring with the immune system and recent data supporting the
      clinical efficacy of probiotic administration in rheumatoid arthritis, multiple
      sclerosis, and myasthenia gravis (MG) animal models. The encouraging results
      suggest that selected strains of probiotics should be evaluated in clinical
      trials as adjuvant therapy to restore the disrupted tolerance in myasthenia
      gravis.

PMID- 29341126
TI  - Size Assessment of the Gray Reef Shark Carcharhinus amblyrhynchos Inferred from
      Teeth Marks on Human Wounds.
AB  - An accurate assessment of the biting shark size is paramount for better
      understanding the agonistic behavior of a species toward humans. The gray reef
      shark is involved in many accidental bites. Based on the capture of 35 gray
      sharks, we calculated the algorithm that allows the assessment of the shark size,
      through the interdental distance (IDD) inferred from teeth marks on human wounds.
      Our results show a negative allometric relationship and that IDD calculated from
      imprints perpetrated by the upper jaw are globally similar with those from the
      lower jaw, in spite of heterodonty. We applied our findings to two cases of
      accidental bites by this species. Both of the victims had declared that the shark
      length was "at least 2 m". Based on our algorithm, the assessment of the shark TL
      was approx. 180 and 160 cm, respectively, which correspond to an overestimation
      of >=20% by the victims.

PMID- 29341127
TI  - Discrimination of Geographical Origin of Asian Garlic Using Isotopic and Chemical
      Datasets under Stepwise Principal Component Analysis.
AB  - Isotopic compositions of delta2 H, delta18 O, delta13 C, and delta15 N and
      concentrations of 22 trace elements from garlic samples were analyzed and
      processed with stepwise principal component analysis (PCA) to discriminate
      garlic's country of origin among Asian regions including South Korea, Vietnam,
      Taiwan, and China. Results indicate that there is no single trace-element
      concentration or isotopic composition that can accomplish the study's purpose and
      the stepwise PCA approach proposed does allow for discrimination between
      countries on a regional basis. Sequentially, Step-1 PCA distinguishes garlic's
      country of origin among Taiwanese, South Korean, and Vietnamese samples; Step-2
      PCA discriminates Chinese garlic from South Korean garlic; and Step-3 and Step-4
      PCA, Chinese garlic from Vietnamese garlic. In model tests, countries of origin
      of all audit samples were correctly discriminated by stepwise PCA. Consequently,
      this study demonstrates that stepwise PCA as applied is a simple and effective
      approach to discriminating country of origin among Asian garlics.

PMID- 29341128
TI  - Study on the Method Used to Display Self-fading Lines and Erasable Lines.
AB  - Two new kinds of writing tools are popular in China's market. One is a self
      fading pen, and another is an erasable pen. The ink of the two kinds of writing
      tools has a remarkable characteristic that it can gradually fade or disappear
      under heat or be rubbed off. How to reveal the disappeared written lines is a
      very important question for document examiners. In this article, three series of
      ink line samples were made with five types of self-fading pens, 18 types of
      erasable pens, and three types of papers. Temperature, humidity, and lighting are
      known as influential factors of the process, and the effect of fading was
      examined. Luminescence, ultraviolet (UV), sidelight, electrostatic indentation
      development,low temperature, and solution revealing methods are found to be
      effective methods used to reveal the disappeared written lines. The best
      operating conditions for each method were obtained from the conducted
      experiments.

PMID- 29341129
TI  - Diagnosing Crime and Diagnosing Disease-II: Visual Pattern Perception and
      Diagnostic Accuracy.
AB  - Previously, we reviewed how general cognitive processes might be susceptible to
      bias across both forensic and clinical fields, and how interdisciplinary
      comparisons could reduce error. We discuss several examples of clinical tasks
      which are heavily dependent on visual processing, comparing them to eyewitness
      identification (EI). We review the "constructive" nature of visual processing,
      and how contextual factors influence both medical experts and witnesses in
      decision making and recall. Overall, studies suggest common cognitive factors
      uniting these visual tasks, in both their strengths and shortcomings. Recently
      forensic sciences have advocated reducing errors by identifying and controlling
      nonrelevant information. Such efforts could effectively assist medical diagnosis.
      We suggest potential remedies for cognitive bias in these tasks. These can
      generalize across the clinical and forensic domains, including controlling the
      sequencing of contextual factors. One solution is an agnostic primary reading
      before incorporation of a complete history and interpretation.

PMID- 29341131
TI  - A retrospective study of feline trauma patients admitted to a referral centre.
AB  - OBJECTIVE: To identify prognostic information and provide recommendations for
      management of feline trauma patients. METHODS: Retrospective analysis of case
      records for 185 cats presented as emergency trauma cases to a referral hospital
      between February 2009 and December 2013. Each case was assigned a severity score
      from 1 (very minor injuries) to 6 (moribund, dying). The data were analysed using
      Mann-Whitney U and Spearman's rank correlation tests. Logistic regression was
      used to calculate odds ratios. RESULTS: Out of 185 cats, 22 (11%) did not survive
      to discharge. Those presenting with a higher severity score had a higher rate of
      mortality and a longer period of hospitalisation. Road traffic accidents were the
      most common cause of trauma (104/185) and had the highest mortality and
      complication rates. Cats with circulatory shock and multiple injuries were
      identified as having a higher rate of mortality. CLINICAL SIGNIFICANCE: Cats
      involved in road traffic accidents and that present with signs of shock or
      multiple injuries following a traumatic event have an increased mortality rate.
      Cats with a higher severity score had an increased duration of hospitalisation.

PMID- 29341133
TI  - Development and initial validity of the in-hand manipulation assessment.
AB  - BACKGROUND/AIM: A review of the literature related to in-hand manipulation (IHM)
      revealed that there is no assessment which specifically measures this construct
      in the adult population. This study reports the face and content validity of an
      IHM assessment for adults with impaired hand function based on expert opinion.
      METHODS: The definition of IHM skills, assessment tasks and scoring methods
      identified from literature was discussed in a focus group (n = 4) to establish
      face validity. An expert panel (n = 16) reviewed the content validity of the
      proposed assessment; evaluating the representativeness and relevance of
      encompassing the IHM skills in the proposed assessment tasks, the clarity and
      importance to daily life of the task and the clarity and applicability to
      clinical environment of the scoring method. The content validity was calculated
      using the content validity index for both the individual task and all tasks
      together (I-CVI and S-CVI). Feedback was incorporated to create the assessment.
      RESULTS: The focus group members agreed to include 10 assessment tasks that
      covered all IHM skills. In the expert panel review, all tasks received an I-CVI
      above 0.78 and S-CVI above 0.80 in representativeness and relevance ratings,
      representing good content validity. With the comments from the expert panel,
      tasks were modified to improve the clarity and importance to daily life. A four
      point Likert scale was identified for assessing both the completion of the
      assessment tasks and the quality of IHM skills within the task performance.
      CONCLUSION: Face and content validity were established in this new IHM
      assessment. Further studies to examine psychometric properties and use within
      clinical practice are recommended.

PMID- 29341132
TI  - Acanthoic acid suppresses lipin1/2 via TLR4 and IRAK4 signalling pathways in EtOH
      and lipopolysaccharide-induced hepatic lipogenesis.
AB  - OBJECTIVES: In alcoholic liver disease, alcohol and lipopolysaccharide (LPS) are
      major stimulation factors of hepatic lipogenesis. Our objective was to determine
      the protective mechanism of acanthoic acid (AA) in EtOH- and LPS-induced hepatic
      lipogenesis. METHODS: HSC-T6 cells were treated with ethanol (200 mm) plus LPS (1
      MUg/ml) for 1 h, followed by AA (10 or 20 MUm) for another 6 h. C57BL/6 mice were
      pretreated with of AA (20 and 40 mg/kg) or equal volume of saline and then
      exposed to three doses of ethanol (5 g/kg body weight) within 24 h. The mice were
      sacrificed at 6 h after the last ethanol dosing. KEY FINDINGS: Acanthoic acid
      significantly decreased the expressions of alpha-SMA, collagen-I, SREBP-1, and
      lipin1/2 induced, also decreased fat droplets caused by EtOH/LPS. AA treatment
      decreased the protein expressions of TLR4, CD14, IRAK4, TRAF3, p-TAK1 and NF
      kappaB increased by EtOH/LPS on HSC cells. Results in vivo were consistent with
      results in vitro. CONCLUSIONS: Our data demonstrated that AA might modulate
      hepatic fibrosis and lipid deposition in HSC-T6 cell stimulated with ethanol
      combined with LPS by decreasing lipin1/2 via TLR4 and IRAK4 signalling pathways,
      and AA might be considered as a potential therapeutic candidate for alcoholic
      liver disease.

PMID- 29341134
TI  - Fatal Hemorrhage from an Arteriovenous Fistula.
AB  - In this study, we present two cases of sudden deaths of people with end-stage
      kidney with arteriovenous fistulas for long-term hemodialysis treatment. This
      procedure is associated with a number of known complications. While stenosis,
      thrombosis, and infection are well known, lethal hemorrhage from arteriovenous
      fistula is much less commonly encountered. Inspection of the bodies at the scene
      of the death by a medical examiner suggested that the deaths were due to
      exsanguination. Autopsies revealed visible defects on the front wall of the
      arteriovenous fistulas. Microscopic examination showed wall necrosis with
      infiltration of various inflammatory cells. Deaths were due to exsanguination
      from the ulcerated arteriovenous fistulas in patients with chronic renal failure.
      Further investigation revealed that complications in the area around the
      arteriovenous fistulas were known and were being treated until a sudden rupture
      of the vessels and hemorrhage from the arteriovenous fistulas resulted in the
      deaths.

PMID- 29341130
TI  - Mitochondrial function and autophagy: integrating proteotoxic, redox, and
      metabolic stress in Parkinson's disease.
AB  - Parkinson's disease (PD) is a movement disorder with widespread neurodegeneration
      in the brain. Significant oxidative, reductive, metabolic, and proteotoxic
      alterations have been observed in PD postmortem brains. The alterations of
      mitochondrial function resulting in decreased bioenergetic health is important
      and needs to be further examined to help develop biomarkers for PD severity and
      prognosis. It is now becoming clear that multiple hits on metabolic and signaling
      pathways are likely to exacerbate PD pathogenesis. Indeed, data obtained from
      genetic and genome association studies have implicated interactive contributions
      of genes controlling protein quality control and metabolism. For example, loss of
      key proteins that are responsible for clearance of dysfunctional mitochondria
      through a process called mitophagy has been found to cause PD, and a significant
      proportion of genes associated with PD encode proteins involved in the autophagy
      lysosomal pathway. In this review, we highlight the evidence for the targeting of
      mitochondria by proteotoxic, redox and metabolic stress, and the role autophagic
      surveillance in maintenance of mitochondrial quality. Furthermore, we summarize
      the role of alpha-synuclein, leucine-rich repeat kinase 2, and tau in modulating
      mitochondrial function and autophagy. Among the stressors that can overwhelm the
      mitochondrial quality control mechanisms, we will discuss 4-hydroxynonenal and
      nitric oxide. The impact of autophagy is context depend and as such can have both
      beneficial and detrimental effects. Furthermore, we highlight the potential of
      targeting mitochondria and autophagic function as an integrated therapeutic
      strategy and the emerging contribution of the microbiome to PD susceptibility.

PMID- 29341136
TI  - Phylogeny and distribution of protein kinase C variants in the zebrafish.
AB  - Conventional protein kinases-consisting of alpha, beta, and gamma family members
      play key roles in numerous signal transduction events. Phylogenetic analysis
      demonstrated the existence of five prkcs (the genes representing PKCs) in
      zebrafish, two paralogous forms of prkca and prkcb and one prkcg variant. mRNA
      expression analysis showed distinct, mainly nervous system specific expression,
      for all five prkc genes. For prkca and prkcb paralogs prominent expression can be
      seen in the telencephalon, in diencephalic regions such as the habenula or the
      optic tectum, in hypothalamic areas and in distinct cerebellar structures. Each
      transcript is additionally expressed in distinct areas: prkcaa is highly abundant
      in cranial sensory ganglia and in dorsal neurons of the hindbrain and the spinal
      cord, prkcab is strongly expressed in additional cerebellar regions, prkcba shows
      expression in the pectoral fin, the otic vesicle and in the proximal convoluted
      tubule of the kidney, and prkcbb shows prominent expression in different
      hypothalamic areas. Expression of prkcg is most striking in the cerebellum. As
      zebrafish PKCs are expressed in structures that are equivalent to mammals, the
      zebrafish model is well suited to study evolutionary conserved functions of PKCs
      in development and disease.

PMID- 29341135
TI  - Phenolic fractions from nine Trifolium species modulate the coagulant properties
      of blood plasma in vitro without cytotoxicity towards blood cells.
AB  - OBJECTIVE: The study covers an evaluation of the influence of extracts (1-50
      MUg/ml), isolated from aerial parts of nine Trifolium L. species (i.e. T.
      alexandrinum, T. fragiferum, T. hybridum, T. incarnatum, T. pallidum, T.
      pratense, T. resupinatum var. majus, T. resupinatum var. resupinatum and T.
      scabrum) on haemostatic properties of blood plasma. METHODS: The clot formation
      and fibrinolysis assay (CFF), blood clotting times, the extrinsic and intrinsic
      coagulation pathway-dependent polymerization of plasma fibrin were measured. The
      effects of plant extracts on amidolytic activity of thrombin were also evaluated
      and compared with argatroban, an antithrombotic drug. Cytotoxicity was assessed
      in a model of blood platelets and as the viability of peripheral blood
      mononuclear cells. KEY FINDINGS: While no changes in blood clotting times or
      fibrinolytic properties of blood plasma were found, some fractions impaired the
      blood plasma coagulation induced by the intrinsic coagulation pathway. Reduction
      in the maximal velocity of fibrin polymerization was also observed in the clot
      formation and fibrinolysis assay. No cytotoxicity of Trifolium extracts towards
      the investigated cells was recorded. CONCLUSIONS: The most efficient
      anticoagulant activity in plasma was found for T. fragiferum and T. incarnatum
      extracts, while the T. alexandrinum fraction was the most effective inhibitor of
      thrombin amidolytic activity.

PMID- 29341137
TI  - Estimation of Chronological Age from Postmortem Tissues Based on Amino Acid
      Racemization.
AB  - Skin and cartilage tissue specimens from 32 male and 13 female corpses aged
      between 17 and 50 years were collected within 24 h after the death. Each specimen
      was analyzed for the composition of dextro (D) and levo (L) forms of aspartate,
      glutamate, and alanine. Linear regression models were constructed using ln [(1 +
      D/L)/(1 - D/L] equation to define the relationship between the extent of
      racemization and the chronological age. Aspartate D/L rates from cartilage showed
      high correlation (r = 0.779, p < 0.001, n = 45). Aspartate D/L rates from skin
      showed very low correlation (r = 0.356, p < 0.002, n = 44). The multilinear
      regression model of both aspartate D/L rates of cartilage and skin tissues in 44
      cases yielded a coefficient of r = 0.828 (p < 0.001). In conclusion, only
      racemization rate of Aspartate both in the skin and the cartilage tissues
      correlated with the chronological age. Our results may imply that the age can be
      estimated more precisely if two different tissue specimens are obtained from one
      corpse.

PMID- 29341138
TI  - Model fitting for small skin permeability data sets: hyperparameter optimisation
      in Gaussian Process Regression.
AB  - OBJECTIVES: The aim of this study was to investigate how to improve predictions
      from Gaussian Process models by optimising the model hyperparameters. METHODS:
      Optimisation methods, including Grid Search, Conjugate Gradient, Random Search,
      Evolutionary Algorithm and Hyper-prior, were evaluated and applied to previously
      published data. Data sets were also altered in a structured manner to reduce
      their size, which retained the range, or 'chemical space' of the key descriptors
      to assess the effect of the data range on model quality. KEY FINDINGS: The Hyper
      prior Smoothbox kernel results in the best models for the majority of data sets,
      and they exhibited significantly better performance than benchmark quantitative
      structure-permeability relationship (QSPR) models. When the data sets were
      systematically reduced in size, the different optimisation methods generally
      retained their statistical quality, whereas benchmark QSPR models performed
      poorly. CONCLUSIONS: The design of the data set, and possibly also the approach
      to validation of the model, is critical in the development of improved models.
      The size of the data set, if carefully controlled, was not generally a
      significant factor for these models and that models of excellent statistical
      quality could be produced from substantially smaller data sets.

PMID- 29341139
TI  - Exploitation of the Ultraviolet Properties and Machine Cut Edges of Paper to
      Associate and Sequence Sheets in a Ream.
AB  - Previously unreported line patterns visible under ultraviolet light were observed
      on a proportion of plain white A4 printer/copier paper from different
      manufacturers. These Ultraviolet Line Patterns (UVLPs) usually appear as stripes
      down the vertical length of the paper. Typically, the UVLPs were found to
      "repeat" through the ream in a predictable way, while also changing. It is
      postulated that the repeating nature of the UVLPs is a result of the way that
      paper is manufactured. This leads to the ability to sequence the sheets compared
      to their original source paper. Even in the absence of UVLPs, it is possible to
      use our observation of the manufacturing process to anticipate the order of
      several sheets of paper and conclusively associate them, in some cases, by
      physically fitting their machine cut edges and crossing paper fibers. Such a
      novel approach to examining questioned documents would be highly useful in
      forensic casework.

PMID- 29341140
TI  - Lipoprotein modifications by gingipains of Porphyromonas gingivalis.
AB  - BACKGROUND AND OBJECTIVE: Several studies have shown an association between
      periodontitis and cardiovascular disease (CVD). Atherosclerosis is the major
      cause of CVD, and a key event in the development of atherosclerosis is
      accumulation of lipoproteins within the arterial wall. Bacteria are the primary
      etiologic agents in periodontitis and Porphyromonas gingivalis is the major
      pathogen in the disease. Several studies support a role of modified low-density
      lipoprotein (LDL) in atherogenesis; however, the pathogenic stimuli that induce
      the changes and the mechanisms by which this occur are unknown. This study aims
      to identify alterations in plasma lipoproteins induced by the periodontopathic
      species of bacterium, P. gingivalis, in vitro. MATERIAL AND METHODS: Plasma
      lipoproteins were isolated from whole blood treated with wild-type and gingipain
      mutant (lacking either the Rgp- or Kgp gingipains) P. gingivalis by
      density/gradient-ultracentrifugation and were studied using 2-dimensional gel
      electrophoresis followed by matrix-assisted laser desorption/ionization mass
      spectrometry. Porphyromonas gingivalis-induced lipid peroxidation and antioxidant
      levels were measured by thiobarbituric acid-reactive substances and antioxidant
      assay kits, respectively, and lumiaggregometry was used for measurement of
      reactive oxygen species (ROS) and aggregation. RESULTS: Porphyromonas gingivalis
      exerted substantial proteolytic effects on the lipoproteins. The Rgp gingipains
      were responsible for producing 2 apoE fragments, as well as 2 apoB-100 fragments,
      in LDL, and the Kgp gingipain produced an unidentified fragment in high-density
      lipoproteins. Porphyromonas gingivalis and its different gingipain variants
      induced ROS and consumed antioxidants. Both the Rgp and Kgp gingipains were
      involved in inducing lipid peroxidation. CONCLUSION: Porphyromonas gingivalis has
      the potential to change the expression of lipoproteins in blood, which may
      represent a crucial link between periodontitis and CVD.

PMID- 29341141
TI  - Dual Effects of Creatinine on the Formation of 2-Amino-1-Methyl-6-Phenylimidazo
      [4,5-b]pyridine (PhIP).
AB  - : Creatinine was found to not only act as a precursor of 2-amino-1-methyl-6
      phenylimidazo [4,5-b]pyridine (PhIP) formation but also inhibit PhIP formation in
      a creatinine/phenylalanine model system. The dual mechanistic effects of
      creatinine on PhIP formation were then investigated in a model system. Adducts of
      creatinine-PhIP were detected by quadrupole-time-of-flight mass spectrometry and
      were found to be a likely explanation for the substantial decrease in the yield
      of PhIP when excess creatinine was supplied. Structures of probable adducts were
      predicted in molecular docking studies, which showed that hydrogen bonds were
      formed between creatinine and PhIP in 1:1 and 2:1 ratios. Furthermore, the active
      sites during creatinine-PhIP adduct formation (the primary amino groups [N2 -]
      and sp2 nitrogen atoms [N3 ] of creatinine and PhIP) match the active sites of
      PhIP metabolism and adducts of PhIP/lipid-derived reactive carbonyls. This
      verifies that creatinine inhibits PhIP production via the formation of adducts
      with hydrogen bonds at the N2 and N3 sites. PRACTICAL APPLICATION: This study
      enhances the understanding of how creatinine affects PhIP formation, reveals a
      new PhIP inhibition mechanism, and will be useful for developing technology to
      control PhIP formation during food processing.

PMID- 29341142
TI  - Evolutionary and genetic features of drug targets.
AB  - In the modern drug discovery pipeline, identification of novel drug targets is a
      critical step. Despite rapid progress in developing biomedical techniques, it is
      still a great challenge to find promising new targets from the ample space of
      human genes. This fact is partially responsible for the situation of "more
      investments, fewer drugs" in the pharmaceutical industry. A series of recent
      researches revealed that successfully targeted genes share some common
      evolutionary and genetic features, which means that the knowledge accumulated in
      modern evolutionary biology and genetics is very helpful to identify potential
      drug targets and to find new drugs as well. In this article, we comprehensively
      summarize the links between human drug targets and genetic diseases and their
      evolutionary origins, with an attempt to introduce these novel concepts and their
      medical implications to the biomedical community.

PMID- 29341143
TI  - Loss of alkaline ceramidase inhibits autophagy in Arabidopsis and plays an
      important role during environmental stress response.
AB  - Sphingolipids, a class of bioactive lipids found in cell membranes, can modulate
      the biophysical properties of the membranes and play a critical role in signal
      transduction. Sphingolipids are involved in autophagy in humans and yeast, but
      their role in autophagy in plants is not well understood. In this study, we
      reported that the AtACER, an alkaline ceramidase that hydrolyses ceramide to long
      chain base (LCB), functions in autophagy process in Arabidopsis. Our empirical
      data showed that the loss of AtACER inhibited autophagy, and its overexpression
      promoted autophagy under nutrient, salinity, and oxidative stresses.
      Interestingly, nitrogen deprivation significantly affected the sphingolipid's
      profile in Arabidopsis thaliana, especially the LCBs. Furthermore, the exogenous
      application of LCBs also induced autophagy. Our findings revealed a novel
      function of AtACER, where it was found to involve in the autophagy process, thus,
      playing a crucial role in the maintenance of a dynamic loop between sphingolipids
      and autophagy for cellular homeostasis under various environmental stresses.

PMID- 29341144
TI  - Role of micro-RNAs in breast cancer surgery.
AB  - BACKGROUND: The management of breast cancer has changed dramatically in the
      molecular era. Micro-RNAs can contribute to multiple facets of cancer surgery.
      METHODS: This narrative review, based on years of research on the role of micro
      RNAs, focused on the potential of these small, robust RNAs to influence all
      aspects of breast cancer surgery. RESULTS: Micro-RNAs have a potential role as
      biomarkers in the diagnosis, prognosis and evaluation of response to therapy in
      breast cancer. They may also contribute to future therapeutic strategies.
      CONCLUSION: The molecular era has changed understanding of cancer. Micro-RNAs
      have the potential for use in personalized cancer strategies.

PMID- 29341145
TI  - Cancer surgery in the genomic era.

PMID- 29341146
TI  - Defining the molecular pathology of pancreatic body and tail adenocarcinoma.
AB  - BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) remains a dismal disease,
      with very little improvement in survival over the past 50 years. Recent large
      scale genomic studies have improved understanding of the genomic and
      transcriptomic landscape of the disease, yet very little is known about molecular
      heterogeneity according to tumour location in the pancreas; body and tail PDACs
      especially tend to have a significantly worse prognosis. The aim was to
      investigate the molecular differences between PDAC of the head and those of the
      body and tail of the pancreas. METHODS: Detailed correlative analysis of
      clinicopathological variables, including tumour location, genomic and
      transcriptomic data, was performed using the Australian Pancreatic Cancer Genome
      Initiative (APGI) cohort, part of the International Cancer Genome Consortium
      study. RESULTS: Clinicopathological data were available for 518 patients
      recruited to the APGI, of whom 421 underwent genomic analyses; 179 of these
      patients underwent whole-genome and 96 RNA sequencing. Patients with tumours of
      the body and tail had significantly worse survival than those with pancreatic
      head tumours (12.1 versus 22.0 months; P = 0.001). Location in the body and tail
      was associated with the squamous subtype of PDAC. Body and tail PDACs enriched
      for gene programmes involved in tumour invasion and epithelial-to-mesenchymal
      transition, as well as features of poor antitumour immune response. Whether this
      is due to a molecular predisposition from the outset, or reflects a later time
      point on the tumour molecular clock, requires further investigation using well
      designed prospective studies in pancreatic cancer. CONCLUSION: PDACs of the body
      and tail demonstrate aggressive tumour biology that may explain worse clinical
      outcomes.

PMID- 29341147
TI  - Genotype and risk of tumour rupture in gastrointestinal stromal tumour.
AB  - BACKGROUND: Tumour rupture is a strong predictor of poor outcome in
      gastrointestinal stromal tumours (GISTs) of the stomach and small intestine. The
      objective was to determine whether tumour genotype was associated with risk of
      rupture. METHODS: Rupture was classified according to the definition proposed by
      the Oslo Sarcoma Group. Since January 2000, data were registered retrospectively
      for all patients at Oslo University Hospital undergoing surgery for localized
      GIST of the stomach or small intestine. Tumour genotype was analysed by Sanger
      sequencing. RESULTS: Two hundred and nine patients with mutation data available
      were identified. Tumour rupture occurred in 37 patients. Among the 155 patients
      with KIT exon 11 mutations, an increased risk of rupture was observed with a
      deletion or insertion-deletion (25 of 86, 29 per cent) compared with
      substitutions (5 of 50, 10 per cent) or duplications/insertions (2 of 19, 11 per
      cent) (P = 0.014). Notably, rupture occurred in 17 of 46 tumours (37 per cent)
      with deletions involving codons 557 and 558 (del557/558) versus 15 of 109 (13.8
      per cent) with other exon 11 mutations (P = 0.002). This association was confined
      to gastric tumours: 12 of 34 (35 per cent) with del557/558 ruptured versus six of
      77 (8 per cent) with other exon 11 mutations (P = 0.001). In multivariable
      logistic regression analysis, del557/558 and tumour size were associated with an
      increased likelihood of tumour rupture, but mitotic count was not. CONCLUSION:
      Gastric GISTs with KIT exon 11 deletions involving codons 557 and 558 are at
      increased risk of tumour rupture. This high-risk feature can be identified in the
      diagnostic evaluation and should be included in the assessment when neoadjuvant
      imatinib treatment is considered.

PMID- 29341148
TI  - Outcomes after prophylactic gastrectomy for hereditary diffuse gastric cancer.
AB  - BACKGROUND: Patients with hereditary diffuse gastric cancer and a CDH1 mutation
      have a 60-80 per cent lifetime risk of developing diffuse gastric cancer. Total
      prophylactic gastrectomy eliminates this risk, but is associated with
      considerable morbidity. The effectiveness (removal of all gastric mucosa) and
      outcomes of this procedure were evaluated retrospectively. METHODS: All
      consecutive individuals undergoing a prophylactic gastrectomy for a CDH1 mutation
      or gastric signet ring cell foci at the authors' institute between 2005 and 2017
      were included. RESULTS: In 25 of 26 patients, intraoperative frozen-section
      examination (proximal resection margin) was used to verify complete removal of
      gastric mucosa. All definitive resection margins were free of gastric mucosa, but
      only after the proximal margin had been reresected in nine patients. In the first
      year after surgery, five of the 26 patients underwent a relaparotomy for
      adhesiolysis (2 patients) or jejunostomy-related complications (3 patients). Six
      patients were readmitted to the hospital within 1 year for nutritional and/or
      psychosocial support (4 patients) or surgical reintervention (2 patients). Mean
      weight loss after 1 year was 15 (95 per cent c.i. 12 to 18) per cent. For the 25
      patients with a follow-up at 1 year or more, functional complaints were reported
      more frequently at 1 year than at 3 months after the operation: bile reflux (15
      versus 11 patients respectively) and dumping (11 versus 7 patients). The majority
      of patients who worked or studied before surgery (15 of 19) had returned fully to
      these activities within 1 year. CONCLUSION: The considerable morbidity and
      functional consequences of gastrectomy should be considered when counselling
      individuals with an inherited predisposition to diffuse gastric cancer.
      Intraoperative frozen-section examination is recommended to remove all risk
      bearing gastric mucosa.

PMID- 29341149
TI  - Quality-of-life implications of risk-reducing cancer surgery.
AB  - BACKGROUND: Modern advances in genetic sequencing techniques have allowed for
      increased availability of genetic testing for hereditary cancer syndromes.
      Consequently, more people are being identified as mutation carriers and becoming
      aware of their increased risk of malignancy. Testing is commonplace for many
      inheritable cancer syndromes, and with that comes the knowledge of being a gene
      carrier for some patients. With increased risk of malignancy, many guidelines
      recommend that gene carriers partake in risk reduction strategies, including risk
      reducing surgery for some syndromes. This review explores the quality-of-life
      consequences of genetic testing and risk-reducing surgery. METHODS: A narrative
      review of PubMed/MEDLINE was performed, focusing on the health-related quality-of
      life implications of surgery for hereditary breast and ovarian cancer, familial
      adenomatous polyposis and hereditary diffuse gastric cancer. RESULTS: Risk
      reducing surgery almost uniformly decreases cancer anxiety and affects patients'
      quality of life. CONCLUSION: Although the overwhelming quality-of-life
      implications of surgery are neutral to positive, risk-reducing surgery is
      irreversible and can be associated with short- and long-term side-effects.

PMID- 29341150
TI  - Effect of Akt activation and experimental pharmacological inhibition on responses
      to neoadjuvant chemoradiotherapy in rectal cancer.
AB  - BACKGROUND: Neoadjuvant chemoradiotherapy (CRT) is one of the preferred initial
      treatment strategies for locally advanced rectal cancer. Responses are variable,
      and most patients still require surgery. The aim of this study was to identify
      molecular mechanisms determining poor response to CRT. METHODS: Global gene
      expression and pathway enrichment were assessed in pretreatment biopsies from
      patients with non-metastatic cT2-4 N0-2 rectal cancer within 7 cm of the anal
      verge. Downstream Akt activation was assessed in an independent set of
      pretreatment biopsies and in colorectal cancer cell lines using
      immunohistochemistry and western blot respectively. The radiosensitizing effects
      of the Akt inhibitor MK2206 were assessed using clonogenic assays and xenografts
      in immunodeficient mice. RESULTS: A total of 350 differentially expressed genes
      were identified, of which 123 were upregulated and 199 downregulated in tumours
      from poor responders. Mitochondrial oxidative phosphorylation (P < 0.001) and
      phosphatidylinositol signalling pathways (P < 0.050) were identified as
      significantly enriched pathways among the set of differentially expressed genes.
      Deregulation of both pathways is known to result in Akt activation, and high
      immunoexpression of phosphorylated Akt S473 was observed among patients with a
      poor histological response (tumour regression grade 0-2) to CRT (75 per cent
      versus 48 per cent in those with a good or complete response; P = 0.016). Akt
      activation was also confirmed in the radioresistant cell line SW480, and a 50 per
      cent improvement in sensitivity to CRT was observed in vitro and in vivo when
      SW480 cells were exposed to the Akt inhibitor MK2206 in combination with
      radiation and 5-fluorouracil. CONCLUSION: Akt activation is a key event in the
      response to CRT. Pharmacological inhibition of Akt activation may enhance the
      effects of CRT. Surgical relevance Organ preservation is an attractive
      alternative in rectal cancer management following neoadjuvant chemoradiotherapy
      (CRT) to avoid the morbidity of radical surgery. Molecular steps associated with
      tumour response to CRT may provide a useful tool for the identification of
      patients who are candidates for no immediate surgery. In this study, tumours
      resistant to CRT were more likely to have activation of specific genetic pathways
      that result in phosphorylated Akt (pAkt) activation. Pretreatment biopsy tissues
      with high immunoexpression of pAkt were more likely to exhibit a poor
      histological response to CRT. In addition, the introduction of a pAkt inhibitor
      to cancer cell lines in vitro and in vivo led to a significant improvement in
      sensitivity to CRT. Identification of pAkt-activated tumours may thus allow the
      identification of poor responders to CRT. In addition, the concomitant use of
      pAkt inhibitors to increase sensitivity to CRT in patients with rectal cancer may
      constitute an interesting strategy for increasing the chance of a complete
      response to treatment and organ preservation.

PMID- 29341152
TI  - Meta-analysis of the prognostic value of CpG island methylator phenotype in
      gastric cancer.
AB  - BACKGROUND: CpG island methylator phenotype (CIMP) has been identified as a
      distinct molecular subtype of gastric cancer, yet associations with survival are
      conflicting. A meta-analysis was performed to estimate the prognostic
      significance of CIMP. METHODS: Embase, MEDLINE, PubMed, PubMed Central and
      Cochrane databases were searched systematically for studies related to the
      association between CIMP and survival in patients undergoing potentially curative
      resection for gastric cancer. RESULTS: A total of 918 patients from ten studies
      were included, and the median proportion of tumours with CIMP-high (CIMP-H)
      status was 40.9 (range 4.8-63) per cent. Gene panels for assessing CIMP status
      varied between the studies. Pooled analysis suggested that specimens exhibiting
      CIMP-H were associated with poorer 5-year survival (odds ratio (OR) for death
      1.48, 95 per cent c.i. 1.10 to 1.99; P = 0.009). Significant heterogeneity was
      observed between studies (I2 = 88 per cent, P < 0.001). Subgroup analysis
      according to whether studies showed a tendency towards poor (5 studies) or
      improved (5) outcomes for patients with CIMP-H tumours, revealed that CIMP-H was
      associated with both poor (OR for death 8.15, 4.65 to 14.28, P < 0.001;
      heterogeneity I2 = 52 per cent, P = 0.08) and improved (OR 0.42, 0.27 to 0.65; P
      < 0.001, heterogeneity I2 = 0 per cent, P = 0.960) survival. CONCLUSION: There
      was heterogeneity in the gene panels used to identify CIMP, which may explain the
      survival differences.

PMID- 29341153
TI  - Circulating tumour cells and DNA as liquid biopsies in gastrointestinal cancer.
AB  - BACKGROUND: Blood is the most extensively studied body fluid and, because it
      contains circulating tumour cells (CTCs) and circulating tumour-derived cell-free
      DNA (ctDNA), it may represent a liquid biopsy for cancer. Methods for enrichment
      and detection of CTCs and ctDNA, their clinical applications and future
      opportunities in gastrointestinal cancers were the focus of this review. METHODS:
      The PubMed database was searched for literature up to 24 June 2017, with a focus
      on the past 10 years. Identified articles were further scrutinized for relevant
      references. Articles were those in English relating to colorectal, gastric and
      pancreatic cancer. RESULTS: Both CTCs and ctDNA are in low abundance compared
      with other cellular components of blood, but effective enrichment and highly
      sensitive techniques are available for their detection. Potential clinical
      applications of these liquid biopsies include screening, prognostic
      stratification, therapy administration, monitoring of treatment effect or
      resistance, and surveillance. Liquid biopsies provide opportunities to reduce the
      need for invasive tissue sampling, especially in the context of intratumoral
      heterogeneity and the need for tumour genotyping. CONCLUSION: Liquid biopsies
      have applications in gastrointestinal cancers to improve clinical decision
      making.

PMID- 29341151
TI  - Gut microbiome influences on anastomotic leak and recurrence rates following
      colorectal cancer surgery.
AB  - BACKGROUND: The pathogenesis of colorectal cancer recurrence after a curative
      resection remains poorly understood. A yet-to-be accounted for variable is the
      composition and function of the microbiome adjacent to the tumour and its
      influence on the margins of resection following surgery. METHODS: PubMed was
      searched for historical as well as current manuscripts dated between 1970 and
      2017 using the following keywords: 'colorectal cancer recurrence', 'microbiome',
      'anastomotic leak', 'anastomotic failure' and 'mechanical bowel preparation'.
      RESULTS: There is a substantial and growing body of literature to demonstrate the
      various mechanisms by which environmental factors act on the microbiome to alter
      its composition and function with the net result of adversely affecting
      oncological outcomes following surgery. Some of these environmental factors
      include diet, antibiotic use, the methods used to prepare the colon for surgery
      and the physiological stress of the operation itself. CONCLUSION: Interrogating
      the intestinal microbiome using next-generation sequencing technology has the
      potential to influence cancer outcomes following colonic resection.

PMID- 29341154
TI  - Emerging methods in colorectal cancer screening.

PMID- 29341155
TI  - Long-term outcome of prophylactic thyroidectomy in children carrying RET germline
      mutations.
AB  - BACKGROUND: A comprehensive assessment has not been undertaken of long-term
      outcomes in children carrying germline RET mutations and undergoing prophylactic
      thyroidectomy with the aim of preventing medullary thyroid cancer (MTC). METHODS:
      A retrospective outcome study (1994-2017) of prophylactic thyroidectomy in
      children, with and without central node dissection, was performed at a tertiary
      surgical centre. RESULTS: Some 167 children underwent prophylactic thyroidectomy,
      109 without and 58 with concomitant central node dissection. In the highest-risk
      mutational category, MTC was found in five of six children (83 per cent) aged 3
      years or less. In the high-risk category, MTC was present in six of 20 children
      (30 per cent) aged 3 years or less, 16 of 36 (44 per cent) aged 4-6 years, and 11
      of 16 (69 per cent) aged 7-12 years (P = 0.081). In the moderate-risk category,
      MTC was seen in one of nine children (11 per cent) aged 3 years or less, one of
      26 (4 per cent) aged 4-6 years, three of 26 (12 per cent) aged 7-12 years, and
      seven of 16 (44 per cent) aged 13-18 years (P = 0.006). Postoperative
      hypoparathyroidism was more frequent in older children (32 per cent in the oldest
      age group versus 3 per cent in the youngest; P = 0.002), whether or not central
      node dissection was carried out. Three children developed recurrent laryngeal
      nerve palsy; all had undergone central node dissection (P = 0.040). All
      complications resolved within 6 months. Postoperative normalization of calcitonin
      serum levels was achieved in 114 (99.1 per cent) of 115 children with raised
      preoperative values. No residual structural disease or recurrence was observed.
      CONCLUSION: Early prophylactic thyroidectomy is a viable surgical concept in
      experienced hands, sparing older children the postoperative morbidity associated
      with delayed neck surgery.

PMID- 29341156
TI  - Introducing genomics into cancer care.

PMID- 29341159
TI  - Clinicopathological, genomic and immunological factors in colorectal cancer
      prognosis.
AB  - BACKGROUND: Numerous factors affect the prognosis of colorectal cancer (CRC),
      many of which have long been identified, such as patient demographics and the
      multidisciplinary team. In more recent years, molecular and immunological
      biomarkers have been shown to have a significant influence on patient outcomes.
      Whilst some of these biomarkers still require ongoing validation, if proven to be
      worthwhile they may change our understanding and future management of CRC. The
      aim of this review was to identify the key prognosticators of CRC, including new
      molecular and immunological biomarkers, and outline how these might fit into the
      whole wider context for patients. METHODS: Relevant references were identified
      through keyword searches of PubMed and Embase Ovid SP databases. RESULTS: In
      recent years there have been numerous studies outlining molecular markers of
      prognosis in CRC. In particular, the Immunoscore(r) has been shown to hold strong
      prognostic value. Other molecular biomarkers are useful in guiding treatment
      decisions, such as mutation testing of genes in the epidermal growth factor
      receptor pathway. However, epidemiological studies continue to show that patient
      demographics are fundamental in predicting outcomes. CONCLUSION: Current
      strategies for managing CRC are strongly dependent on clinicopathological
      staging, although molecular testing is increasingly being implemented into
      routine clinical practice. As immunological biomarkers are further validated,
      their testing may also become routine. To obtain clinically useful information
      from new biomarkers, it is important to implement them into a model that includes
      all underlying fundamental factors, as this will enable the best possible
      outcomes and deliver true precision medicine.

PMID- 29341157
TI  - Minimizing inequality in access to precision medicine in breast cancer by real
      time population-based molecular analysis in the SCAN-B initiative.
AB  - BACKGROUND: Selection of systemic therapy for primary breast cancer is currently
      based on clinical biomarkers along with stage. Novel genomic tests are
      continuously being introduced as more precise tools for guidance of therapy,
      although they are often developed for specific patient subgroups. The Sweden
      Cancerome Analysis Network - Breast (SCAN-B) initiative aims to include all
      patients with breast cancer for tumour genomic analysis, and to deliver molecular
      subtype and mutational data back to the treating physician. METHODS: An
      infrastructure for collection of blood and fresh tumour tissue from all patients
      newly diagnosed with breast cancer was set up in 2010, initially including seven
      hospitals within the southern Sweden regional catchment area, which has 1.8
      million inhabitants. Inclusion of patients was implemented into routine clinical
      care, with collection of tumour tissue at local pathology departments for
      transport to the central laboratory, where routines for rapid sample processing,
      RNA sequencing and biomarker reporting were developed. RESULTS: More than 10 000
      patients from nine hospitals have currently consented to inclusion in SCAN-B with
      high (90 per cent) inclusion rates from both university and secondary hospitals.
      Tumour samples and successful RNA sequencing are being obtained from more than 70
      per cent of patients, showing excellent representation compared with the national
      quality registry as a truly population-based cohort. Molecular biomarker reports
      can be delivered to multidisciplinary conferences within 1 week. CONCLUSION:
      Population-based collection of fresh tumour tissue is feasible given a decisive
      joint effort between academia and collaborative healthcare groups, and with
      governmental support. An infrastructure for genomic analysis and prompt data
      output paves the way for novel systemic therapy for patients from all hospitals,
      irrespective of size and location.

PMID- 29341160
TI  - Genetic analysis of surgical margins in oral cavity cancer.
AB  - BACKGROUND: A histological, tumour-free surgical margin does not guarantee
      recurrence-free survival in patients with cancer. This study investigated the
      association between microsatellite alteration in tumour-free surgical margins and
      local recurrence in patients with oral cavity squamous cell carcinoma. METHODS:
      Patients with histologically confirmed oral cavity squamous cell carcinoma were
      enrolled in this prospective study. Cancerous specimens, corresponding surgical
      margins and peripheral blood were obtained. Microsatellite alteration was
      investigated using six dinucleotide microsatellite markers. All samples were
      amplified by PCR, followed by automatic fragment analysis. RESULTS:
      Microsatellite alteration was identified in 100 specimens (69.0 per cent) from
      145 patients. Among them, 85 specimens carried loss of heterozygosity, whereas 55
      had microsatellite instability (MSI). Patients with MSI at the surgical margin
      had a higher risk of local recurrence on multivariable analysis (odds ratio 7.17,
      95 per cent c.i. 3.49 to 14.73). CONCLUSION: Molecular assessment of surgical
      margins can help identify patients at risk of local recurrence.

PMID- 29341161
TI  - Modalities for image- and molecular-guided cancer surgery.
AB  - BACKGROUND: Surgery is the cornerstone of treatment for many solid tumours. A
      wide variety of imaging modalities are available before surgery for staging,
      although surgeons still rely primarily on visual and haptic cues in the operating
      environment. Image and molecular guidance might improve the adequacy of resection
      through enhanced tumour definition and detection of aberrant deposits.
      Intraoperative modalities available for image- and molecular-guided cancer
      surgery are reviewed here. METHODS: Intraoperative cancer detection techniques
      were identified through a systematic literature search, with selection of peer
      reviewed publications from January 2012 to January 2017. Modalities were
      reviewed, described and compared according to 25 predefined characteristics. To
      summarize the data in a comparable way, a three-point rating scale was applied to
      quantitative characteristics. RESULTS: The search identified ten image- and
      molecular-guided surgery techniques, which can be divided into four groups:
      conventional, optical, nuclear and endogenous reflectance modalities.
      Conventional techniques are the most well known imaging modalities, but
      unfortunately have the drawback of a defined resolution and long acquisition
      time. Optical imaging is a real-time modality; however, the penetration depth is
      limited. Nuclear modalities have excellent penetration depth, but their
      intraoperative use is limited by the use of radioactivity. Endogenous reflectance
      modalities provide high resolution, although with a narrow field of view.
      CONCLUSION: Each modality has its strengths and weaknesses; no single technique
      will be suitable for all surgical procedures. Strict selection of modalities per
      cancer type and surgical requirements is required as well as combining techniques
      to find the optimal balance.

PMID- 29341162
TI  - Impact of genomics on the surgical management of melanoma.
AB  - BACKGROUND: Although surgery for early-stage melanoma offers the best chance of
      cure, recent advances in molecular medicine have revolutionized the management of
      late-stage melanoma, leading to significant improvements in clinical outcomes.
      Research into the genomic drivers of disease and cancer immunology has not only
      ushered in a new era of targeted and immune-based therapies for patients with
      metastatic melanoma, but has also provided new tools for monitoring disease
      recurrence and selecting therapeutic strategies. These advances present new
      opportunities and challenges to the surgeon treating patients with melanoma.
      METHODS: The literature was reviewed to evaluate diagnostic and therapeutic
      advances in the management of cutaneous melanoma, and to highlight the impact of
      these advances on surgical decision-making. RESULTS: Genomic testing is not
      required in the surgical management of primary melanoma, although it can provide
      useful information in some situations. Circulating nucleic acids from melanoma
      cells can be detected in peripheral blood to predict disease recurrence before it
      manifests clinically, but validation is required before routine clinical
      application. BRAF mutation testing is the standard of care for all patients with
      advanced disease to guide therapy, including the planning of surgery in adjuvant
      and neoadjuvant settings. CONCLUSION: Surgery remains central for managing
      primary melanoma, and is an important element of integrated multidisciplinary
      care in advanced disease, particularly for patients with resectable metastases.
      The field will undergo further change as clinical trials address the
      relationships between surgery, radiotherapy and systemic therapy for patients
      with high-risk, early-stage and advanced melanoma.

PMID- 29341163
TI  - Extent of surgery for phaeochromocytomas in the genomic era.
AB  - BACKGROUND: Germline mutations are present in 20-30 per cent of patients with
      phaeochromocytoma. For patients who develop bilateral disease, complete removal
      of both adrenal glands (total adrenalectomy) will result in lifelong adrenal
      insufficiency with an increased risk of death from adrenal crisis.
      Unilateral/bilateral adrenal-sparing surgery (subtotal adrenalectomy) offers
      preservation of cortical function and independence from steroids, but leaves the
      adrenal medulla in situ and thus at risk of developing new and possibly malignant
      disease. Here, present knowledge about how tumour genotype relates to clinical
      behaviour is reviewed, and application of this knowledge when choosing the extent
      of adrenalectomy is discussed. METHODS: A literature review was undertaken of the
      penetrance of the different genotypes in phaeochromocytomas, the frequency of
      bilateral disease and malignancy, and the underlying pathophysiological
      mechanisms, with emphasis on explaining the clinical phenotypes of
      phaeochromocytomas and their associated syndromes. RESULTS: Patients with
      bilateral phaeochromocytomas most often have multiple endocrine neoplasia type 2
      (MEN2) or von Hippel-Lindau disease (VHL) with high-penetrance mutations for
      benign disease, whereas patients with mutations in the genes encoding SDHB
      (succinate dehydrogenase subunit B) or MAX (myelocytomatosis viral proto-oncogene
      homologue-associated factor X) are at increased risk of malignancy. CONCLUSION:
      Adrenal-sparing surgery should be the standard approach for patients who have
      already been diagnosed with MEN2 or VHL when operating on the first side, whereas
      complete removal of the affected adrenal gland(s) is generally recommended for
      patients with SDHB or MAX germline mutations. Routine assessment of a patient's
      genotype, even after the first operation, can be crucial for adopting an
      appropriate strategy for follow-up and future surgery.

PMID- 29341165
TI  - Histopathological and molecular classification of colorectal cancer and
      corresponding peritoneal metastases.
AB  - BACKGROUND: Patients with colorectal peritoneal carcinomatosis have a very poor
      prognosis. The recently developed consensus molecular subtype (CMS)
      classification of primary colorectal cancer categorizes tumours into four robust
      subtypes, which could guide subtype-targeted therapy. CMS4, also known as the
      mesenchymal subtype, has the greatest propensity to form distant metastases. CMS4
      status and histopathological features of colorectal peritoneal carcinomatosis
      were investigated in this study. METHODS: Fresh-frozen tissue samples from
      primary colorectal cancer and paired peritoneal metastases from patients who
      underwent cytoreductive surgery combined with hyperthermic intraperitoneal
      chemotherapy were collected. Histopathological features were analysed, and a
      reverse transcriptase-quantitative PCR test was used to assess CMS4 status of all
      collected lesions. RESULTS: Colorectal peritoneal carcinomatosis was associated
      with adverse histopathological characteristics, including a high percentage of
      stroma in both primary tumours and metastases, and poor differentiation grade and
      high-grade tumour budding in primary tumours. Furthermore, CMS4 was significantly
      enriched in primary tumours with peritoneal metastases, compared with unselected
      stage I-IV tumours (60 per cent (12 of 20) versus 23 per cent; P = 0.002). The
      majority of peritoneal metastases (75 per cent, 21 of 28) were also classified as
      CMS4. Considerable intrapatient subtype heterogeneity was observed. Notably, 15
      of 16 patients with paired tumours had at least one CMS4-positive tumour
      location. CONCLUSION: Significant enrichment for CMS4 was observed in colorectal
      peritoneal carcinomatosis. Surgical relevance Cytoreductive surgery combined with
      hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) improves survival of
      selected patients with colorectal peritoneal carcinomatosis, but recurrence is
      common. Histopathological and molecular analysis of colorectal peritoneal
      carcinomatosis could provide clues for development of novel therapies. In this
      study, colorectal peritoneal carcinomatosis was found to be enriched for tumours
      with high stromal content and CMS4-positive status. To further improve prognosis
      for patients with colorectal peritoneal carcinomatosis, therapies that target
      tumour-stroma interaction could be added to CRS-HIPEC.

PMID- 29341167
TI  - The Influence of Colloid Osmotic Pressure on Hydrostatic Pressures in High- and
      Low-Flux Hemodialyzers.
AB  - The aim of this study was to examine the relationship between hydrostatic trans
      membrane pressure (TMPh ) and colloid osmotic pressure (COP) in low-flux (LF) and
      high-flux (HF) dialyzers. Hydrostatic pressures were measured in dialyzers
      distinguished by their ultrafiltration coefficient Kuf (16 and 85 mL/h/mm Hg)
      under constant dialysate flow and variable blood flow (Qb ) ranging from 0 to 400
      mL/min using (i) alginate (70 kDa) dissolved in dialysate, (ii) diluted,
      undiluted, and concentrated plasma, or (iii) whole blood at different hematocrit,
      all in absence of ultrafiltration (UF). For a given fluid, TMPh linearly
      increased with increasing Qb . The intercept of the linear TMPh to Qb
      relationship correlated with measured COP with an average bias of 1.00 +/- 2.26
      mm Hg and a concordance correlation coefficient of 0.98. The slope of the linear
      TMPh to Qb relationship increased with increasing sample viscosity and was much
      larger in HF dialyzers under otherwise identical operating conditions, most
      likely because of increased internal filtration. The TMPh to Qb relationship
      measured in dialyzers in absence of UF can be described by the intercept related
      to measured COP and the slope related to internal filtration. This relationship
      could be of interest to estimate internal filtration and COP under in vivo
      conditions.

PMID- 29341164
TI  - Patient-derived organoid models help define personalized management of
      gastrointestinal cancer.
AB  - BACKGROUND: The prognosis of patients with different gastrointestinal cancers
      varies widely. Despite advances in treatment strategies, such as extensive
      resections and the addition of new drugs to chemotherapy regimens, conventional
      treatment strategies have failed to improve survival for many tumours. Although
      promising, the clinical application of molecularly guided personalized treatment
      has proven to be challenging. This narrative review focuses on the
      personalization of cancer therapy using patient-derived three-dimensional
      'organoid' models. METHODS: A PubMed search was conducted to identify relevant
      articles. An overview of the literature and published protocols is presented, and
      the implications of these models for patients with cancer, surgeons and
      oncologists are explained. RESULTS: Organoid culture methods have been
      established for healthy and diseased tissues from oesophagus, stomach, intestine,
      pancreas, bile duct and liver. Because organoids can be generated with high
      efficiency and speed from fine-needle aspirations, biopsies or resection
      specimens, they can serve as a personal cancer model. Personalized treatment
      could become a more standard practice by using these cell cultures for extensive
      molecular diagnosis and drug screening. Drug sensitivity assays can give a
      clinically actionable sensitivity profile of a patient's tumour. However, the
      predictive capability of organoid drug screening has not been evaluated in
      prospective clinical trials. CONCLUSION: High-throughput drug screening on
      organoids, combined with next-generation sequencing, proteomic analysis and other
      state-of-the-art molecular diagnostic methods, can shape cancer treatment to
      become more effective with fewer side-effects.

PMID- 29341168
TI  - In search of a counter you can count on: relative efficacy of human visual and
      automated colony counting.
AB  - : To evaluate comparative efficiency of traditional vs automated colony counting
      methods, cultures of Escherichia coli (ATCC 25945), Staphylococcus epidermidis
      (ATCC 12225), Streptococcus pyogenes (ATCC19615) and Streptococcus pneumoniae
      (ATCC49619) were prepared as pure cultures and mixed cultures at 0.5 McFarland
      standard and serial dilutions were performed. Plates were inoculated in
      triplicate with 50, 125, 250 and 500 colony forming units and counted by four
      researchers, visually and using each of the automated counters. Colony count and
      counting time were recorded. The pattern of efficiency for all bacterial species
      was similar: plates with low counts were accurate and quick to count for all
      methods, with an increase in time and a decrease in accuracy and precision as
      counts rose. Higher counts of single round colonies required less time and had
      greater precision with automated counters than human visual counting counts with
      no loss of accuracy; however, counts were reduced in accuracy and increased in
      time for species with less regular morphology or when plates had mixed species.
      Surprisingly, a free phone application was only slightly less precise and more
      time consuming than the high-end professional counter indicating that automation
      may be achievable at lower cost than expected. SIGNIFICANCE AND IMPACT OF THE
      STUDY: Colony quantification is essential in clinical and research settings as
      well as pedagogy at the college level. Human visual (HV) counting, the most
      common method, is time consuming and fraught with errors. The time, accuracy and
      precision of HV counting were compared to a high-end professional automated
      counter, an inexpensive phone application and a free phone application. Low cost
      benefits of increased speed and accuracy with automated counting are maximized
      when counting single round colonies; but much reduced if colonies have irregular
      morphology or demonstrate haemolysis.

PMID- 29341169
TI  - False-positive result when a diphenylcarbazide spot test is used on trivalent
      chromium-passivated zinc surfaces.
AB  - BACKGROUND: A colorimetric 1,5-diphenylcarbazide (DPC)-based spot test can be
      used to identify hexavalent chromium on various metallic and leather surfaces.
      DPC testing on trivalent chromium-passivated zinc surfaces has unexpectedly given
      positive results in some cases, apparently indicating the presence of hexavalent
      chromium; however, the presence of hexavalent chromium has never been confirmed
      with more sensitive and accurate test methods. OBJECTIVES: To examine the
      presence of hexavalent chromium on trivalent chromium-passivated zinc surfaces
      with a DPC-based spot test. METHODS: A colorimetric DPC spot test was used for
      the initial detection of hexavalent chromium on new and 1-year-aged trivalent
      chromium-passivated zinc surfaces. Then, X-ray photoelectron spectroscopy (XPS)
      was performed for all samples. RESULTS: The DPC spot test indicated the presence
      of hexavalent chromium in aged, but not new, trivalent chromium passivation on
      zinc; however, subsequent analysis by XPS could not confirm the presence of
      chromium in a hexavalent state. CONCLUSIONS: Unintended oxidation of DPC induced
      by atmospheric corrosion is suggested as a possible reason for the false-positive
      reaction of the DPC test on a trivalent chromium-passivated zinc surface. Further
      validation of the use of the DPC test for chromium-containing metallic surfaces
      is required.

PMID- 29341172
TI  - Statin use and the risk of cardiovascular implantable electronic device
      infection: A cohort study in a veteran population.
AB  - BACKGROUND: The rate of cardiovascular implantable electronic device infection
      (CIEDI) has increased, despite the use of perioperative antibiotics at the time
      of device placement or revision. This is due, in part, to the presence of
      multiple comorbid conditions in an elderly population, in general, who require
      CIED. Statins may have an antibacterial effect, although there is currently no
      evidence that the likelihood of CIEDI has been impacted by statin use. METHODS: A
      retrospective cohort study was performed to assess whether statins are associated
      with a reduced risk of CIEDI. The VA Informatics and Computing Infrastructure
      (VINCI) database, which includes all veterans who underwent CIED placement
      between 2008 and 2015, was used. A logistic regression model was constructed to
      estimate the adjusted risk of CIEDI among patients who were receiving statins
      after adjusting for confounding factors. RESULTS: Overall, 18,970 CIED procedures
      were included, and 98% of them were performed in men with a mean age of 71 +/- 11
      years. The rate of diabetes mellitus, heart failure, advanced chronic kidney
      diseases, CIEDI, positive methicillin-resistant Staphylococcus aureus nasal
      colonization, and statin use were 23%, 15.7%, 3.3%, 1.14%, 12.6%, and 56%,
      respectively. The logistic regression analysis showed that statins were
      significantly associated with a reduced risk of CIEDI; after controlling for
      other effects, the reduction was 66% (odds ratio 0.34 [0.2-0.59], P-value <
      0.001). The effect of statins was confirmed by propensity score analysis.
      CONCLUSIONS: Our study showed that among patients receiving statins who had
      undergone CIED placement, there was a 66% reduction in subsequent CIEDI.

PMID- 29341170
TI  - Identification and characterization of a new three-component nicotinic acid
      hydroxylase NahAB1 B2 from Pusillimonas sp. strain T2.
AB  - : Nicotinic acid (NA) is ubiquitous in nature and its microbial degradation
      mechanisms are diverse. In this study, Pusillimonas sp. strain T2 was found to be
      capable of utilizing NA as sole carbon and nitrogen sources. This strain could
      completely degrade 300 mg l-1 NA within 3.5 h at 30 degrees C and pH 7.0 and one
      of the degradation intermediate of NA was identified as 6-hydroxynicotinic acid
      (6HNA). The draft genome sequences of strain T2 were determined to have a total
      length of 3.3 M bp and 3054 proteins were predicted. The encoding genes of three
      component NA hydroxylase (NahAB1 B2 ) genes were identified. The nahAB1 B2 genes
      were heterologously expressed in the non-NA-degrading Shinella sp. strain HZN7.
      The recombinant HZN7-pBBR-nahAB1 B2 converted NA into equimolar 6HNA, while the
      recombinants HZN7-pBBR-nahAB1 (lacking component B2 ) and HZN7-pBBR-nahAB2
      (lacking component B1 ) could not convert NA. Cell-free extracts of HZN7-pBBR
      nahAB1 B2 exhibited NA hydroxylase activity. After addition of an artificial
      electron acceptor (such as phenazine methosulphate, PMS), the NA hydroxylase
      activity was significantly increased. The Km and Vmax values for NA were 65.94
      MUmol l-1 and 260.80 +/- 5.69 mU mg-1 , respectively, using PMS as an electron
      acceptor. This study provides a novel insight into the NA degradation by
      bacteria. SIGNIFICANCE AND IMPACT OF THE STUDY: Nicotinic acid (NA) serves as a
      model system for the degradation of N-heterocyclic aromatic compounds and the
      microbial degradation mechanisms are diverse. This is the first time that a three
      component hydroxylase has been identified. This study provides a novel insight
      into the NA degradation by bacteria.

PMID- 29341173
TI  - Strigolactones positively regulate chilling tolerance in pea and in Arabidopsis.
AB  - Strigolactones (SL) fulfil important roles in plant development and stress
      tolerance. Here, we characterized the role of SL in the dark chilling tolerance
      of pea and Arabidopsis by analysis of mutants that are defective in either SL
      synthesis or signalling. Pea mutants (rms3, rms4, and rms5) had significantly
      greater shoot branching with higher leaf chlorophyll a/b ratios and carotenoid
      contents than the wild type. Exposure to dark chilling significantly decreased
      shoot fresh weights but increased leaf numbers in all lines. Moreover, dark
      chilling treatments decreased biomass (dry weight) accumulation only in rms3 and
      rms5 shoots. Unlike the wild type plants, chilling-induced inhibition of
      photosynthetic carbon assimilation was observed in the rms lines and also in the
      Arabidopsis max3-9, max4-1, and max2-1 mutants that are defective in SL synthesis
      or signalling. When grown on agar plates, the max mutant rosettes accumulated
      less biomass than the wild type. The synthetic SL, GR24, decreased leaf area in
      the wild type, max3-9, and max4-1 mutants but not in max2-1 in the absence of
      stress. In addition, a chilling-induced decrease in leaf area was observed in all
      the lines in the presence of GR24. We conclude that SL plays an important role in
      the control of dark chilling tolerance.

PMID- 29341174
TI  - Sensing performance, safety, and patient acceptability of long-dipole cardiac
      monitor: An innovative axillary insertion.
AB  - BACKGROUND: The recommended location for implantable cardiac monitor (ICM)
      insertion is the left pectoral region. We tested whether an innovative left
      axillary implantation approach could be applicable for a new ICM, characterized
      by a long sensing dipole. METHODS: We considered a series of 55 patients
      consecutively implanted with a long-dipole ICM (BioMonitor 2); the first 30
      subjects underwent prepectoral location insertion, while the subsequent 25
      received the ICM in the axillary region. Sensing performances collected at 1
      month follow-up were compared between the two groups. During the visit, each
      patient was also asked to fill in a brief questionnaire to assess patient
      acceptability of the device. RESULTS: All patients had a successful insertion of
      ICM. Mean R-wave amplitude was 0.87 +/- 0.44 mV in the prepectoral group and 1.00
      +/- 0.45 mV in the axillary one, without any significant difference. The
      percentage of patients with visible P wave was also comparable between the two
      approaches (65.5% vs 68.2%, P = 0.84). None of the patients reported device
      related issues or discomfort, and ICM was generally well accepted and tolerated
      by all the involved patients. CONCLUSION: Axillary insertion may represent a
      valid alternative to the standard one for long-dipole ICM technology providing
      not only patient acceptability but also high-quality sensing performances.

PMID- 29341175
TI  - Investigation of the Axial Gap Clearance in a Hydrodynamic-Passive Magnetically
      Levitated Rotary Blood Pump Using X-Ray Radiography.
AB  - The HeartWare HVAD is a radial rotary blood pump with a combination of passive
      magnetic and hydrodynamic bearings to levitate the impeller. The axial gap size
      between impeller and housing in this bearing and its sensitivity to speed, flow,
      and pressure difference is difficult to assess. Shear stresses are exceptionally
      high in this tiny gap making it important for blood damage and related adverse
      events. Therefore, the aim of this study was to measure the axial gap clearance
      in the HVAD at different operating conditions employing radiography. To quantify
      the gap size in the HVAD, the pump was positioned 30 mm in front of the X-ray
      source employing a microfocus X-ray tube with an acceleration voltage up to 300
      kV. Beams were detected on a flat panel detector (Perkin Elmer XRD 1611-CP3). The
      pump was connected to a tubing circuit with a throttle to adjust flow (0, 5, 10
      L/min) and a water glycerol mixture to set the desired viscosity (1, 4, 8 mPas).
      Rotational speed was varied between 1800 and 3600 rpm. In this study, for
      clinically relevant conditions at 5 L/min and 2700 rpm, the axial gap was 22 um.
      The gap size increased with rotational speeds dependent on the viscosity (2.8,
      6.9, and 9.4 um/1000 rpm for 1, 4, and 8 mPas, respectively), but was independent
      from the volume flow and the pressure head at constant speeds. In summary, using
      X-ray radiographic imaging small gaps in a rotary blood pump during operation can
      be measured in a nondestructive contact-free way. The axial hydrodynamic bearing
      gap in the HVAD pump was determined to be in the range of about three times the
      diameter of a red blood cell. Its dependence on operating volume flow and
      generated pressure head across the pump is not pronounced.

PMID- 29341176
TI  - Different responses of supraventricular tachycardia with 2:1 AV block to
      consecutive premature ventricular contractions.

PMID- 29341177
TI  - Prevalence of antinuclear and anti-erythrocyte antibodies in healthy cats.
AB  - BACKGROUND: Positive antinuclear antibody and direct antiglobulin tests support
      diagnoses such as systemic lupus erythematosus and immune-mediated anemia,
      respectively. Positive tests may occur in cats, but the prevalence of positive
      results in healthy cats is not well known. OBJECTIVE: The study's purpose was to
      determine prevalences of positive antinuclear antibody and direct antiglobulin
      tests in healthy cats. METHODS: Antinuclear antibody titers were measured by
      indirect immunofluorescence, and anti-erythrocyte antibodies were measured by the
      microtitration direct antiglobulin test at 37, 23, and 4 degrees C in 61 client
      owned and 28 facility-owned cats. Differences between the 2 groups were examined
      using chi-squared tests. RESULTS: For the antinuclear antibody tests, 70% of
      client-owned cats were negative, 10% had weak titers (1:40-1:80), and 20% had
      strong titers (1:160-1:320). Facility-owned cats had significantly fewer positive
      titers with 96% negative and one positive (1:8). For the antiglobulin test at 37
      degrees C, 93% of all cats were negative, 2 cats in each group were positive at
      low dilutions (1:2), and 2 client-owned cats were transiently positive at high
      dilutions (>= 1:2048). At 23 degrees C, 90% of all cats were negative, and 2
      client-owned and 5 facility-owned cats were positive at low dilutions (1:2-1:8).
      At 4 degrees C, 67% of client-owned cats had invalid results (negative control
      well agglutination), and 33% had negative results, while of facility-owned cats
      14% had invalid results, 14% had agglutination at low dilutions, and 72% were
      negative. CONCLUSION: Healthy cats may have positive antinuclear antibody and
      direct antiglobulin tests, but the prevalence of strong reactions is low.

PMID- 29341178
TI  - Security Investment in Contagious Networks.
AB  - Security of the systems is normally interdependent in such a way that security
      risks of one part affect other parts and threats spread through the vulnerable
      links in the network. So, the risks of the systems can be mitigated through
      investments in the security of interconnecting links. This article takes an
      innovative look at the problem of security investment of nodes on their
      vulnerable links in a given contagious network as a game-theoretic model that can
      be applied to a variety of applications including information systems. In the
      proposed game model, each node computes its corresponding risk based on the value
      of its assets, vulnerabilities, and threats to determine the optimum level of
      security investments on its external links respecting its limited budget.
      Furthermore, direct and indirect nonlinear influences of a node's security
      investment on the risks of other nodes are considered. The existence and
      uniqueness of the game's Nash equilibrium in the proposed game are also proved.
      Further analysis of the model in a practical case revealed that taking advantage
      of the investment effects of other players, perfectly rational players (i.e.,
      those who use the utility function of the proposed game model) make more cost
      effective decisions than selfish nonrational or semirational players.

PMID- 29341179
TI  - Better characterization of vinflunine pharmacokinetics variability and
      exposure/toxicity relationship to improve its use: Analyses from 18 trials.
AB  - AIMS: Vinflunine is a novel tubulin-targeted inhibitor indicated as a single
      agent for the treatment of bladder cancers after failure of prior platinum-based
      therapy. Its pharmacokinetics (PK) and pharmacodynamics (PD) have been
      independently characterized through several phase I and phase II studies.
      However, no global pharmacometric analysis had been conducted as yet. METHODS:
      Vinflunine concentrations and safety data from 18 phase I and phase II studies
      were used to conduct population PK and PK/PD analysis, using Nonmem. A four
      compartment model was used to describe vinflunine PK and several covariates were
      tested to explain interindividual variability. In terms of PK/PD relationship, a
      semiphysiological population PK/PD model was applied to describe time course of
      absolute neutrophil counts (ANC) after vinflunine administration and logistic
      regression models were used to test the relationship between vinflunine exposure
      and toxicities. RESULTS: Vinflunine clearance is explained by creatinine
      clearance, body surface area and combination with PEGylated doxorubicin, leading
      to a decrease from 28.2 to 25.3% of the interindividual variability. When
      vinflunine dose is decreased, simulations of ANC time course (via a
      semiphysiological model) after vinflunine administration show a risk of
      neutropenia grade 3-4 at cycle 2 always lower than when dose is delayed. As an
      example, for moderate renal impaired patients, the risk is 42.1% when vinflunine
      is dosed at 320 mg m-2 once every 4 weeks vs. 23.3% for 280 mg m-2 once every 3
      weeks. CONCLUSIONS: We propose for the first time a global comprehensive clinical
      pharmacological analysis for intravenous vinflunine that may help drive dose
      adjustment.

PMID- 29341180
TI  - Risk Assessment of Salmonellosis from Consumption of Alfalfa Sprouts and
      Evaluation of the Public Health Impact of Sprout Seed Treatment and Spent
      Irrigation Water Testing.
AB  - We developed a risk assessment of human salmonellosis associated with consumption
      of alfalfa sprouts in the United States to evaluate the public health impact of
      applying treatments to seeds (0-5-log10 reduction in Salmonella) and testing
      spent irrigation water (SIW) during production. The risk model considered
      variability and uncertainty in Salmonella contamination in seeds, Salmonella
      growth and spread during sprout production, sprout consumption, and Salmonella
      dose response. Based on an estimated prevalence of 2.35% for 6.8 kg seed batches
      and without interventions, the model predicted 76,600 (95% confidence interval
      (CI) 15,400-248,000) cases/year. Risk reduction (by 5- to 7-fold) predicted from
      a 1-log10 seed treatment alone was comparable to SIW testing alone, and each
      additional 1-log10 seed treatment was predicted to provide a greater risk
      reduction than SIW testing. A 3-log10 or a 5-log10 seed treatment reduced the
      predicted cases/year to 139 (95% CI 33-448) or 1.4 (95% CI <1-4.5), respectively.
      Combined with SIW testing, a 3-log10 or 5-log10 seed treatment reduced the
      cases/year to 45 (95% CI 10-146) or <1 (95% CI <1-1.5), respectively. If the SIW
      coverage was less complete (i.e., less representative), a smaller risk reduction
      was predicted, e.g., a combined 3-log10 seed treatment and SIW testing with 20%
      coverage resulted in an estimated 92 (95% CI 22-298) cases/year. Analysis of
      alternative scenarios using different assumptions for key model inputs showed
      that the predicted relative risk reductions are robust. This risk assessment
      provides a comprehensive approach for evaluating the public health impact of
      various interventions in a sprout production system.

PMID- 29341181
TI  - Baboon syndrome caused by anti-haemorrhoidal ointment.

PMID- 29341182
TI  - Allergic contact dermatitis caused by Olanedine(r) (olanexidine gluconate), a new
      antiseptic.

PMID- 29341183
TI  - Systemic delayed hypersensitivity reaction to chlorambucil: a case report and
      literature review.

PMID- 29341184
TI  - First report of allergic contact dermatitis caused by sorbitan caprylate.

PMID- 29341185
TI  - Comparing patch test results of methylchloroisothiazolinone/methylisothiazolinone
      tested with both TRUE Test(r) and 100 ppm using investigator-loaded chambers.

PMID- 29341186
TI  - 'Chaturthy fingers' caused by Hibiscus rosasinensis.

PMID- 29341187
TI  - Erythema of the penis after use of a latex condom - latex allergy or something
      else?

PMID- 29341188
TI  - Allergic contact dermatitis caused by hydroxyacetophenone in a face cream.

PMID- 29341189
TI  - Is p-phenylenediamine a marker of sulfasalazine allergy?

PMID- 29341190
TI  - First case report of acute generalized exanthematous pustulosis (AGEP) caused by
      gadolinium confirmed by patch testing.

PMID- 29341191
TI  - Working and caring for a child with chronic illness: A review of current
      literature.
AB  - BACKGROUND: Advances in medical knowledge have contributed to the increase in the
      number of children living with some form of long-term chronic illness or
      condition. As a consequence of these advancements, treatments that are more
      accessible and easier to administer, usually within a child's home, have been
      developed. However, this may mean that parents take on greater treatment
      responsibility and require extra time and energy to meet these tasks, additional
      to other responsibilities. This review paper aims to summarize and critique
      existing literature on working parents of children with a chronic condition, by
      focusing on patterns of parent work, the challenges experienced, and the flow-on
      consequences to well-being. METHODS: Employing a narrative, meta-synthesis of the
      current literature, this review identified 3 key themes related to working
      parents of children with chronic illness. RESULTS: The paper first identifies
      that although employment is less common, these parents are not necessarily
      nonworking. Second, these parents experience numerous challenges including
      balancing work and family, time constraints, stress, and feelings of "doing it
      all." And third, the above challenges lead to additional impacts on parental
      quality of life. CONCLUSIONS: This review summarizes what is currently known
      about work patterns, challenges, and consequences in parents of children with
      chronic conditions. Employment is clearly impacted for these parents. Although
      workplace challenges have been extensively researched, other challenges (eg,
      personal and family) and impacts on their well-being have not. This review
      discusses the present standing of this research. It outlines the strengths and
      limitations of the current literature, makes recommendations for future research,
      and suggests theoretical and practical implications of the further findings.

PMID- 29341192
TI  - Population Pharmacokinetic Modeling of Guselkumab, a Human IgG1lambda Monoclonal
      Antibody Targeting IL-23, in Patients with Moderate to Severe Plaque Psoriasis.
AB  - Psoriasis is a common inflammatory skin disorder that requires chronic treatment
      and is associated with multiple comorbidities. Guselkumab, a human immunoglobulin
      G1-lambda monoclonal antibody, binds to interleukin-23 with high specificity and
      affinity and is effective in treating moderate to severe plaque psoriasis. As
      part of the guselkumab psoriasis clinical trial program, using a confirmatory
      approach, a population pharmacokinetics (PopPK) model was established using 13
      014 PK samples from 1454 guselkumab-treated patients across 3 phase 2/3 trials.
      Observed serum guselkumab concentrations were adequately described by a 1
      compartment linear PK model with first-order absorption and elimination. The
      final PK model was robust and stable, with apparent clearance (CL/F), apparent
      volume of distribution (V/F), and absorption rate constant (ka) estimates of
      0.516 L/day, 13.5 L, and 1.11 day-1 , respectively. A model-derived elimination
      half-life of 18.1 days indicated achievement of steady-state serum guselkumab
      concentrations within 12-14 weeks. The primary covariate contributing to the
      observed PK variability was body weight, which accounted for only 28% (CL/F) and
      32% (V/F) of the interindividual proportion of variance. Diabetes was identified
      to marginally reduce guselkumab exposure, owing to 12% higher CL/F in diabetic
      versus nondiabetic patients, but its contribution was not clinically relevant.
      None of the other covariates tested (eg, age, sex, ethnicity, immune response to
      guselkumab, or concomitant medications) had a clinically relevant effect on
      guselkumab exposure.

PMID- 29341193
TI  - Impact of Trans-Fats on Heat-Shock Protein Expression and the Gut Microbiota
      Profile of Mice.
AB  - Partially hydrogenated oils are known to cause metabolic stress and dyslipidemia.
      This paper explores a new dimension about the interaction between dietary trans
      fats and the defense heat-shock protein (HSP) system, inflammation, and the gut
      microbiota of mice consuming a hyperlipidic diet containing partially
      hydrogenated vegetable oil free of animal fat. Five diet groups were installed:
      control diet, 2 hyperlipidic-partially hydrogenated-oil diets, each containing
      either casein or whey-protein hydrolysate (WPH) as protein source, and 2
      consuming hyperlipidic-unhydrogenated-oil diets containing either WPH or casein
      as a protein source. The partially hydrogenated oil inhibited c-Jun NH2 -terminal
      kinase phosphorylation in the casein diets, but without altering kappa-B kinase.
      Neither the lipid nor the protein had an influence on the proinflammatory toll
      like receptor 4 (TLR4) pathway, but the combination of the high-lipid content and
      WPH impaired glucose tolerance without altering insulin or glucose transporter-4
      translocation. It was remarkable to observe that, contrary to the case of a
      common high-fat diet, the lard-free hyperlipidic diets were hardly able to invert
      the Bacteroidetes:Firmicutes phylum ratio. Our results suggest that, in the
      absence of lard, the intake of trans-fatty acids is less harmful than expected
      because it does not trigger TLR4-inflammation or pose great threat to the normal
      gut microbiota. WPH had the effect of promoting the expression of HSP90, HSP60,
      and HSP25, but did not prevent dysbiosis, when the diet contained the
      unhydrogenated oil. The partially hydrogenated oil also seemed to antagonize the
      ability of WPH to induce the expression of protective HSPs.

PMID- 29341194
TI  - Generation of red drum (Sciaenops ocellatus) hematology Reference Intervals with
      a focus on identified outliers.
AB  - BACKGROUND: The Deepwater Horizon (DWH) oil spill in 2010 released millions of
      barrels of crude oil into the northern Gulf of Mexico, exposing numerous species
      of animals to the toxic components of oil. A comprehensive assessment of
      morbidity and mortality caused by DWH oil exposure was undertaken by the DWH
      Natural Resource Damage Trustees to characterize ecosystem damages. OBJECTIVES:
      This study aimed to characterize normal hematologic RIs in red drum fish with
      blood cell descriptions, and to demonstrate the importance of identifying and
      removing outliers when generating RI. METHODS: Two years after the oil spill, 57
      adult, red drum fish of mixed sexes were caught along the eastern Louisiana
      coastline. Eight different sites were chosen to catch the fish; 6 sites were
      contaminated with oil, and 2 sites were not contaminated at the time of the oil
      spill. Hematologic RIs were generated from heparinized whole blood samples of
      healthy red drum as determined by gross examination and histopathologic
      examination. Two methods were used to detect hematologic effects likely caused by
      oil contamination. RESULTS: Red drum PCVs (RI 42-62%) were higher than previously
      reported in cold water and bottom-dwelling fish species, while absolute WBC
      counts (RI 2.9-8.7  * 109 /L) were comparable to WBC counts previously reported
      in other fish species with heterophil and lymphocyte absolute concentrations
      frequently being equivalent. Anemic animals (PCV<42%) were only identified in oil
      contaminated sites. CONCLUSION: RIs in many wild fish species are lacking, and
      therefore, this study provides valuable baseline data on healthy red drum fish.
      The outliers assessed using ASVCP RI guidelines can provide valuable clinical
      information regarding individuals in population health assessments, which may be
      more sensitive for the detection of abnormalities than for population statistics
      comparing the mean. The importance of removing outliers and rerunning RI
      statistics is highlighted by this field example.

PMID- 29341195
TI  - Association between circulating 25-hydroxyvitamin D levels and psoriasis, and
      correlation with disease severity: a meta-analysis.
AB  - BACKGROUND: Psoriasis is a chronic, autoimmune, inflammatory skin disorder. 25
      hydroxy vitamin D [25(OH)D] deficiency may contribute to the pathogenesis of
      psoriasis through reduction in antiproliferative, anti-inflammatory and
      antiangiogenic activities. AIM: To evaluate the relationship between circulating
      25(OH)D levels and psoriasis, and to determine the correlation between
      serum/plasma 25(OH)D levels and psoriasis severity. METHODS: We performed a meta
      analysis to compare serum/plasma 25(OH)D levels between patients with psoriasis
      and healthy controls (HCs), and to determine the correlation coefficients between
      circulating 25(OH)D levels and psoriasis severity as assessed by Psoriasis Area
      and Severity Index (PASI). RESULTS: Ten articles with a total of 571 patients
      with psoriasis and 496 HCs were included. The 25(OH)D level was significantly
      lower in the psoriasis group than in the HC group. Subgroup analysis by sample
      size revealed a significantly lower level of 25(OH)D in the psoriasis group for
      large (N > 80) but not for small (N < 80) sample sizes. Stratification by
      adjustment for age and/or sex or sample type revealed a significantly lower
      25(OH)D level in the psoriasis group after adjustment for serum but not after
      nonadjustment for plasma. Meta-analysis of the correlation coefficients revealed
      a small but statistically significant positive correlation between circulating
      25(OH)D levels and PASI. CONCLUSIONS: This meta-analysis demonstrated that
      circulating 25(OH)D levels are lower in patients with psoriasis, and that a small
      but statistically significant negative correlation exists between 25(OH)D levels
      and psoriasis severity.

PMID- 29341196
TI  - Dynamic Economic Resilience and Economic Recovery from Disasters: A Quantitative
      Assessment.
AB  - This article analyzes the role of dynamic economic resilience in relation to
      recovery from disasters in general and illustrates its potential to reduce
      disaster losses in a case study of the Wenchuan earthquake of 2008. We first
      offer operational definitions of the concept linked to policies to promote
      increased levels and speed of investment in repair and reconstruction to
      implement this resilience. We then develop a dynamic computable general
      equilibrium (CGE) model that incorporates major features of investment and traces
      the time-path of the economy as it recovers with and without dynamic economic
      resilience. The results indicate that resilience strategies could have
      significantly reduced GDP losses from the Wenchuan earthquake by 47.4% during
      2008-2011 by accelerating the pace of recovery and could have further reduced
      losses slightly by shortening the recovery by one year. The results can be
      generalized to conclude that shortening the recovery period is not nearly as
      effective as increasing reconstruction investment levels and steepening the time
      path of recovery. This is an important distinction that should be made in the
      typically vague and singular reference to increasing the speed of recovery in
      many definitions of dynamic resilience.

PMID- 29341197
TI  - How reliable are commercially available trackers in detecting daytime sleep.

PMID- 29341198
TI  - Aicardi-Goutieres syndrome: cold-induced acral blemish is not always
      cryoglobulinaemic vasculitis or chilblain lupus.

PMID- 29341199
TI  - Timing of gamma irradiation and blood donor sex influences in vitro
      characteristics of red blood cells.
AB  - BACKGROUND: There are few studies investigating the effect of irradiation on red
      blood cells (RBCs) during storage. This study analyzed changes in in vitro
      quality of RBCs irradiated at several points during storage with the aim of
      providing evidence to support current maximum pre- and postirradiation storage
      limits. STUDY DESIGN AND METHODS: Each of seven participating centers produced
      four pools of 7 standard RBC units (SAGM, AS-3, or PAGGSM), which were then split
      back into 7 units. All units in a pool were from sex-matched blood donors. Every
      week during 6 weeks of refrigerated storage, 1 unit was irradiated, while 1 unit
      was not irradiated (control). Units were tested weekly for biochemical variables,
      morphology, and mechanical fragility. RESULTS: The earlier during storage that
      units were irradiated, the higher the hemolysis and K+ at end of storage.
      Irrespective of the timing of irradiation, there was a rapid increase in
      extracellular K+ , followed by a more gradual increase in hemolysis. ATP levels
      decreased faster in irradiated units and were reduced below accepted values if
      irradiated early. Irradiated female RBCs had an absolute lower hemolysis and K+
      level compared to male RBCs at all time points. CONCLUSIONS: The method of blood
      component manufacturing determined the absolute levels of hemolysis and potassium
      in irradiated and nonirradiated units, but did not influence the effect that
      timing of irradiation had on the in vitro quality characteristics. This study
      provides support for the current Council of Europe guidelines on the time
      limitations for the irradiation of RBCs.

PMID- 29341200
TI  - Human Agency in Disaster Planning: A Systems Approach.
AB  - Current approaches to risk management place insufficient emphasis on the system
      knowledge available to the assessor, particularly in respect of the dynamic
      behavior of the system under threat, the role of human agents (HAs), and the
      knowledge available to those agents. In this article, we address the second of
      these issues. We are concerned with a class of systems containing HAs playing a
      variety of roles as significant system elements-as decisionmakers, cognitive
      agents, or implementers-that is, human activity systems. Within this family of
      HAS, we focus on safety and mission-critical systems, referring to this subclass
      as critical human activity systems (CHASs). Identification of the role and
      contribution of these human elements to a system is a nontrivial problem whether
      in an engineering context, or, as is the case here, in a wider social and public
      context. Frequently, they are treated as standing apart from the system in design
      or policy terms. Regardless of the process of policy definition followed,
      analysis of the risk and threats to such a CHAS requires a holistic approach,
      since the effect of undesirable, uninformed, or erroneous actions on the part of
      the human elements is both potentially significant to the system output and
      inextricably bound together with the nonhuman elements of the system. We present
      a procedure for identifying the potential threats and risks emerging from the
      roles and activity of those HAs, using the 2014 flooding in southwestern England
      and the Thames Valley as a contemporary example.

PMID- 29341201
TI  - Diversity in cancer care: exploring social categories in encounters between
      healthcare professionals and breast cancer patients.
AB  - BACKGROUND: The burden of breast cancer is a key challenge for women's health
      globally. Rehabilitation needs and strategies for living with long-term
      consequences of breast cancer and its treatment cannot be isolated from the
      social contexts of patients, including relationships with relatives and
      healthcare professionals. AIM: This study explores how healthcare professionals'
      categorisations engage with breast cancer patients' social identities in
      encounters about rehabilitation before hospital discharge. METHOD: We conducted a
      multiperspective case-based qualitative study at a Danish department of breast
      surgery, including participant observations and interviews with twelve patients
      and eight nurses. Data were analysed thematically using theories of
      categorisation and clinical encounters. Ethical considerations: The Danish Data
      Protection Agency approved the study (journal number 2012-41-0701). RESULTS:
      Interactions in clinical encounters are shaped by categorisations of patients'
      social identities in terms of social resources and ethnicity, and by the resource
      constrained organisational context, with impact on the assessments of the
      patient's rehabilitation needs. CONCLUSIONS: There is a need for a greater focus
      on improving encounters between breast cancer patients and healthcare
      professionals to ensure that rehabilitation needs are accommodated for among
      diverse patient groups.

PMID- 29341202
TI  - Risk factors for stress urinary incontinence recurrence after single-incision
      sling.
AB  - AIMS: The aim of the study was to identify in a pure stress urinary incontinence
      (SUI) population risk factors for recurrence after single-incision slings (SIS).
      METHODS: This retrospective study analyzed women with complaints of SUI symptoms
      and urodynamically proven SUI. Exclusion criteria were recurrent SUI, overactive
      bladder syndrome/detrusor overactivity, preoperative postvoid residual >100 mL,
      reduced urethral mobility (<10 degrees  at the Q-tip test), concomitant anterior
      prolapse >I stage and previous history of radical pelvic surgery. Objective cure
      rate was assessed with stress test. RESULTS: A total of 192 patients were
      analyzed. Objective cure rate was obtained in 86.5% of patients. According to
      univariate analysis, recurrences had higher prevalence of severe ICIQ-SF score
      (>=18 points), higher prevalence of reduced urethral mobility (Qtip <=30 degrees
      ), higher prevalence of low detrusor pressures during voiding phase (opening
      pressure <15 cmH2 O, pressure at maximum flow <20 cmH2 O, closing pressure <15
      cmH2 O), and higher prevalence of postoperative complications According to
      multivariate analysis ICIQ-SF score >=18 points (P = 0.02; OR = 2.7) and detrusor
      pressure at maximum flow <20 cmH2 O (P < 0.01; OR = 3.6) resulted as independent
      risk factors for SUI recurrence (Table 3). A trend was found for urethral
      mobility <=30 degrees  (P = 0.07; OR = 2.2). CONCLUSIONS: Our study identifies
      SUI severity expressed with ICIQ-SF scores and low detrusor pressure at maximum
      flow as independent risk factors for SUI recurrence after SIS implantation while
      only a trend was found for reduced urethral mobility. Therefore, preoperative
      assessment of symptoms and urodynamics evaluation may play a key role in
      improving preoperative counseling and tailoring surgical treatment.

PMID- 29341203
TI  - Food specific inhibitory control under negative mood in binge-eating disorder:
      Evidence from a multimethod approach.
AB  - OBJECTIVE: Inhibitory control has been discussed as a developmental and
      maintenance factor in binge-eating disorder (BED). The current study is the first
      aimed at investigating inhibitory control in a negative mood condition on a
      psychophysiological and behavioral level in BED with a combination of
      electroencephalography (EEG) and eye tracking (ET). METHOD: We conducted a
      combined EEG and ET study with overweight individuals with BED (BED+, n = 24,
      mean age = 31, mean BMI = 35 kg/m2 ) and without BED (BED-, n = 23, mean age =
      28, mean BMI = 35 kg/m2 ) and a normal-weight (NWC, n = 26, mean age 28, mean BMI
      = 22 kg/m2 ) control group. We assessed self-report data regarding impulsivity
      and emotion regulation as well as the processing of food stimuli under negative
      mood in an antisaccade task. Main outcome variables comprise event-related
      potentials (ERP) regarding conflict processing (N2) and performance monitoring
      (error-related negativity [ERN/Ne]) assessed by EEG and inhibitory control
      (errors in the first and second saccade) assessed by ET. RESULTS: BED+ patients
      reported increased impulsivity and higher emotion regulation difficulties
      compared with the other groups. The eye tracking data revealed impaired
      inhibitory control in BED+ compared with both control groups. Further, we found
      preliminary evidence from EEG recordings that conflict processing might be less
      thorough in the BED+ sample as well as in the NWC sample. In the BED+ sample this
      might be connected to the inhibitory control deficits on behavioral level. While
      the BED- sample showed increased conflict processing latencies (N2 latencies),
      which might indicate a compensation mechanism, the BED+ sample did not show such
      a mechanism. Performance monitoring (ERN/Ne latencies and amplitudes) was not
      impaired in the BED+ sample compared with both control samples. DISCUSSION:
      Participants with BED reported higher impulsivity and lower emotion regulation
      capacities. The combined investigation of electrocortical processes and behavior
      contributes to an advanced understanding of behavioral and electrocortical
      processes underlying inhibitory control in BED. Inhibitory control and negative
      mood, probably amplified by emotion regulation deficits, should be addressed
      further in the investigation and treatment of BED.

PMID- 29341205
TI  - Promotion time cure rate model with nonparametric form of covariate effects.
AB  - Survival data with a cured portion are commonly seen in clinical trials.
      Motivated from a biological interpretation of cancer metastasis, promotion time
      cure model is a popular alternative to the mixture cure rate model for analyzing
      such data. The existing promotion cure models all assume a restrictive parametric
      form of covariate effects, which can be incorrectly specified especially at the
      exploratory stage. In this paper, we propose a nonparametric approach to modeling
      the covariate effects under the framework of promotion time cure model. The
      covariate effect function is estimated by smoothing splines via the optimization
      of a penalized profile likelihood. Point-wise interval estimates are also derived
      from the Bayesian interpretation of the penalized profile likelihood. Asymptotic
      convergence rates are established for the proposed estimates. Simulations show
      excellent performance of the proposed nonparametric method, which is then applied
      to a melanoma study.

PMID- 29341204
TI  - Gender, parental education, and experiences of bullying victimization by
      Australian adolescents with and without a disability.
AB  - BACKGROUND: This study sought to compare the prevalence of bullying victimization
      between adolescents with and without a disability and between adolescents with
      and without borderline intellectual functioning or intellectual disability
      (BIF/ID). We also sought to assess whether the relationships between either
      disability or BIF/ID and bullying victimization vary by gender and parental
      education. METHODS: The sample included 3,956 12- to 13-year-old adolescents who
      participated in Wave 5 of the Longitudinal Study of Australian Children. Three
      indicators of bullying were used: physical bullying victimization, social
      bullying victimization, and "any bullying victimization." We used Poisson
      regression to obtain the prevalence risk ratios (PRR) of bullying by disability
      status adjusting for potential confounders. RESULTS: In adjusted models, we found
      evidence that social bullying victimization was more prevalent among adolescents
      with a disability than those without a disability (PRR 1.29, 95% confidence
      interval [CI] 1.06-1.42) and between adolescents with BIF/ID than those without
      (PRR 1.24, 95% CI 1.07-1.44). Adolescents with BIF/ID were also more likely to
      experience "any bullying victimization"(PRR 1.10, 95% CI 1.00-1.22). Having a
      disability and living in a family with low parental education were associated
      with an elevated risk of social bullying victimization BIF/ID. CONCLUSIONS:
      Adolescents with disabilities and BIF/ID are at elevated risk of social bullying
      victimization. School-based antibullying initiatives should concentrate on
      enhancing the inclusion of adolescents with disabilities, with an emphasis on
      adolescents from disadvantaged backgrounds.

PMID- 29341207
TI  - Letters to the editor.

PMID- 29341206
TI  - Validation of a portable monitor for assessment of cerebrospinal fluid lactate in
      dogs.
AB  - BACKGROUND: Cerebrospinal fluid (CSF) lactate concentration may be a useful
      diagnostic and prognostic biomarker in dogs. Previous studies have used methods
      requiring relatively large sample volumes or prolonged storage prior to analysis.
      An effective method to immediately quantify lactate in smaller CSF volumes would
      be beneficial. OBJECTIVES: The main objectives were to evaluate the utility,
      accuracy, and precision of a portable meter for CSF lactate analysis in dogs and
      to develop a provisional RI using this device. A secondary objective was to
      assess the effects of different storage conditions on lactate concentrations.
      METHODS: The Lactate Plus device was used to analyze CSF samples. Device accuracy
      and precision were assessed by spiking CSF samples with concentrated sodium
      lactate solutions and by repeated analysis of samples, respectively. The
      provisional RI was generated using CSF samples from dogs with unremarkable
      laboratory data, central nervous system imaging, and conventional cytologic and
      chemical CSF analysis. Select samples were analyzed before and after storage at 4
      degrees C, -20 degrees C, and -80 degrees C. RESULTS: Spiked samples showed
      lactate concentrations comparable to expected concentrations. The CV of immediate
      repeated measurements was 0-9.69%. Sample storage at 4 degrees C for 24 hours
      showed similar results but variation was higher with other storage conditions.
      The provisional RI was 1.02-2.49 mmol/L. CONCLUSIONS: The Lactate Plus has
      acceptable accuracy and precision for the quantification of CSF lactate in dogs.
      Lactate in CSF is ideally quantified immediately after collection as a subset of
      samples show variation with storage although most stored samples show acceptable
      variation.

PMID- 29341208
TI  - Letters to the editor.

PMID- 29341209
TI  - Identification of gaps in the current knowledge on pulmonary hypertension in
      extremely preterm infants: A systematic review and meta-analysis.
AB  - BACKGROUND: Pulmonary hypertension complicates the clinical course of extremely
      preterm infants and is associated with bronchopulmonary dysplasia (BPD). However,
      prevalence, risk factors, and outcome of pulmonary hypertension in these infants
      are insufficiently known. This systematic review and meta-analysis aims to
      provide an up-to-date overview of available data on prevalence, risk factors, and
      outcome of pulmonary hypertension and to identify current knowledge gaps.
      METHODS: Medline, EMBASE, and the Cochrane Library databases were searched in
      July 2017. Two authors reviewed titles/abstracts and full-texts. Eligible studies
      reported prevalence, patient characteristics or mortality of infants with/without
      pulmonary hypertension. Studies were excluded if they did not include extremely
      preterm infants. Only similar study samples (selected infants with BPD or infants
      both with/without BPD) were compared in the meta-analyses. RESULTS: Of 1829
      unique articles identified, 25 were eligible for inclusion. Pulmonary
      hypertension was observed in infants with BPD (20%, 95% confidence interval [CI]
      14, 25), but also in those without BPD (2%, 95% CI 0, 8). Infants with severe BPD
      were most at risk of pulmonary hypertension (risk ratio [RR] 2.7, 95% CI 1.7,
      4.2). Infants with pulmonary hypertension were more at risk of mortality (RR 4.7,
      95% CI 2.7, 8.3). CONCLUSIONS: Pulmonary hypertension occurs in particularly in
      infants with severe BPD, and increases risk of mortality. Due to selected study
      populations, heterogeneous pulmonary hypertension-definitions and poorly reported
      timing of pulmonary hypertension assessments, however, data available in current
      reports are insufficient to allow accurate assessment of true prevalence, risk
      factors, and time-related outcome. Prospective studies, with standardised
      methodology and follow-up are needed to determine these factors.

PMID- 29341210
TI  - Subchorionic Hematoma: Correlation of Grading Techniques With First-Trimester
      Pregnancy Outcome.
AB  - OBJECTIVES: To evaluate and compare grading systems of subchorionic hematoma
      (SCH) on first-trimester ultrasound examinations with live embryos to assess
      which best correlates with early pregnancy outcome and to assess the effect of
      gestational age at the time of diagnosis on outcome. METHODS: First-trimester
      live singleton pregnancies between 6 and 11 weeks' gestational age with SCH were
      identified by an institutional database search. First-trimester outcome was
      categorized as "live" or "demise" based on ultrasound or medical record
      documentation. Hematomas were categorized in 4 ways: (1) subjective (small,
      moderate, or large); (2) subjective size based on fraction comparison with
      gestational sac size; (3) subjective grading based on the estimated percentage of
      the gestational sac surrounded by hematoma; and (4) 3 orthogonal measurements of
      the hematoma. RESULTS: A total of 434 sonograms met study inclusion criteria. The
      overall rate of first-trimester pregnancy failure was 12.0%. The rate of demise
      was significantly higher for hematomas diagnosed at or before 7 weeks (19.6%)
      than for those after 8 weeks (3.6%; P < .001). The size of the hematoma estimated
      as a fraction of gestational sac size significantly correlated with first
      trimester pregnancy loss (P < .001). There was no statistical significance
      between first-trimester outcome and the other 2 subjective grading methods.
      Volume-based measurements provided spurious results because of the irregular
      shape of most hematomas. CONCLUSIONS: Subjective hematoma size based on the
      fraction of gestational sac size correlates best with first-trimester pregnancy
      outcome. The earlier in pregnancy an SCH is detected, the higher the rate of
      subsequent pregnancy failure.

PMID- 29341213
TI  - Detection of subclinical left ventricular dysfunction by tissue Doppler imaging
      in horses with aortic regurgitation.
AB  - BACKGROUND: Aortic regurgitation (AR) can have an important clinical impact and
      in some cases leads to left ventricular (LV) failure. Tissue Doppler imaging
      (TDI) is an echocardiographic technique that has been used in horses to detect LV
      dysfunction. OBJECTIVES: To examine whether TDI detects changes in radial
      myocardial wall motion in horses with AR compared with control horses. STUDY
      DESIGN: Case-control study. METHODS: Echocardiography was performed in 30 healthy
      Warmblood horses and 34 Warmblood horses with AR, subdivided in groups with mild,
      moderate or severe AR. TDI measurements were performed on six segments of the
      short-axis images of the LV myocardial wall. Myocardial wall motion was evaluated
      by measuring velocity and deformation during isovolumetric contraction, systole,
      early and late diastole. Timing of different events was also measured. RESULTS:
      In most segments, a significantly higher systolic myocardial velocity was found
      in horses with AR compared with controls. Horses with AR also had higher late
      diastolic velocity, although the difference was not significant in all segments.
      TDI measurement of timing intervals demonstrated less difference between groups.
      MAIN LIMITATIONS: There was a significant difference in age between the control
      group and horses with AR, which may confound the results. The assessment of AR
      severity was based on subjective criteria as there is no gold standard.
      CONCLUSIONS: TDI showed significant differences in radial systolic and late
      diastolic myocardial velocity in horses with AR. This could indicate an altered
      LV function in these horses, but further research is needed to investigate the
      prognostic value of these measurements.

PMID- 29341212
TI  - Differential role of PTEN in transforming growth factor beta (TGF-beta) effects
      on proliferation and migration in prostate cancer cells.
AB  - BACKGROUND: Transforming growth factor-beta (TGF-beta) acts as a tumor suppressor
      in normal epithelial cells but as a tumor promoter in advanced prostate cancer
      cells. PI3-kinase pathway mediates TGF-beta effects on prostate cancer cell
      migration and invasion. PTEN inhibits PI3-kinase pathway and is frequently
      mutated in prostate cancers. We investigated possible role(s) of PTEN in TGF-beta
      effects on proliferation and migration in prostate cancer cells. METHODS:
      Expression of PTEN mRNA and proteins were determined using RT-PCR and Western
      blotting in RWPE1 and DU145 cells. We also studied the role of PTEN in TGF-beta
      effects on cell proliferation and migration in DU145 cells after transient
      silencing of endogenous PTEN. Conversely, we determined the role of PTEN in cell
      proliferation and migration after over-expression of PTEN in PC3 cells which lack
      endogenous PTEN. RESULTS: TGF-beta1 and TGF-beta3 had no effect on PTEN mRNA
      levels but both isoforms increased PTEN protein levels in DU145 and RWPE1 cells
      indicating that PTEN may mediate TGF-beta effects on cell proliferation.
      Knockdown of PTEN in DU145 cells resulted in significant increase in cell
      proliferation which was not affected by TGF-beta isoforms. PTEN overexpression in
      PC3 cells inhibited cell proliferation. Knockdown of endogenous PTEN enhanced
      cell migration in DU145 cells, whereas PTEN overexpression reduced migration in
      PC3 cells and reduced phosphorylation of AKT in response to TGF-beta. CONCLUSION:
      We conclude that PTEN plays a role in inhibitory effects of TGF-beta on cell
      proliferation whereas its absence may enhance TGF-beta effects on activation of
      PI3-kinase pathway and cell migration.

PMID- 29341215
TI  - MicroRNA181c inhibits prostate cancer cell growth and invasion by targeting
      multiple ERK signaling pathway components.
AB  - BACKGROUND: The ERK signaling pathway is frequently deregulated in tumorigenesis,
      mostly by classical mechanisms such as gene mutation of its components (eg, RAS
      and RAF). However, whether and how multiple key components of ERK pathway are
      regulated by microRNAs are not clear. METHODS: We firstly predicted post
      transcriptional regulation of multiple key components of the ERK signaling
      pathway by miR181c through bioinformatics analysis, and then confirmed the post
      transcriptional regulation by dual luciferase reporter gene assays and Western
      blot analysis. The biological effects of miR181c on prostate cancer cell
      proliferation, apoptosis, migration, and invasion were measured by CCK-8 assay,
      flow cytometry, wound scratch assay, transwell cell migration, and invasion
      assays. RESULTS: miR181c post-transcriptionally regulated multiple key members of
      the ERK signaling pathway, including extracellular signal-regulated kinase 2
      (ERK2), ribosomal S6 kinase 2 (RSK2), serum response factor (SRF), and FBJ murine
      osteosarcoma viral oncogene homolog (c-Fos). Ectopic expression of miR181c mimics
      effectively suppressed prostate cancer cell proliferation, migration, and
      invasion, but promoted cell apoptosis. Furthermore, miR181c treatment combined
      with the multi-kinase inhibitor sorafenib significantly enhanced these anti-tumor
      effects. CONCLUSIONS: Downregulation of miR181c results in deregulated ERK
      signaling and promotes prostate cancer cell growth and metastasis.

PMID- 29341214
TI  - Cue reactivity, habituation, and eating in the absence of hunger in children with
      loss of control eating and attention-deficit/hyperactivity disorder.
AB  - OBJECTIVE: Childhood loss of control (LOC) eating and attention
      deficit/hyperactivity disorder (ADHD) are highly comorbid conditions and present
      with disordered eating behaviors, such as overeating. This study sought to
      delineate shared and specific abnormalities in physiological, cognitive
      motivational, and behavioral components of food-specific impulsivity in children
      with LOC eating and ADHD. Specifically, children's reactivity and habituation to
      food and eating in the absence of hunger were examined. METHODS: Within this
      community-based study, four groups of 8-13-year-old children with LOC eating (n =
      24), ADHD (n = 32), comorbid LOC eating/ADHD (n = 9), and matched controls (n =
      34) received a standard laboratory test meal to establish satiety and were then
      exposed to their favorite snack food in a cue exposure/reactivity trial, while
      salivation and desire to eat were repeatedly assessed. Subsequently, they were
      offered a variety of snack foods ad libitum. RESULTS: Children with LOC eating,
      ADHD, and LOC/ADHD did not differ from controls in salivary reactivity and
      habituation to food cues. Children with LOC eating and ADHD showed greater cue
      reactivity of the desire to eat than controls, but groups did not differ in its
      longer-term increments. At free access, only children with LOC/ADHD consumed
      significantly more energy than controls. Longer-term increments of desire to eat
      predicted greater energy intake beyond LOC/ADHD group status. DISCUSSION: Desire
      to eat among children with comorbid LOC eating and ADHD was associated with
      overeating in the absence of hunger, which may contribute to excess weight gain.
      Delineation of the specific features of childhood LOC eating versus ADHD warrants
      further study.

PMID- 29341216
TI  - Primary scarring alopecia: A retrospective study of 89 patients in Taiwan.
AB  - Primary scarring alopecia (PSA) is caused by irreversible damage to the hair
      epithelial stem cells that reside in hair follicles. There is limited published
      work regarding PSA amongst the Asian population. The aim of this study was to
      evaluate the clinical features and to characterize the subtypes of PSA in
      southern Taiwan. In this retrospective case series, we reviewed 89 patients with
      pathology-confirmed PSA. The data was collected from National Cheng Kung
      University Hospital between 1988 through 2016. The clinical and histological data
      were reviewed, and the patients were characterized into different subtypes of PSA
      based on the clinical features and histological findings. We noted seven
      different subtypes of PSA. The most common type was dissecting cellulitis (DC)
      (30.3%), followed by lichen planopilaris (LPP) (23.5%), central centrifugal
      cicatricial alopecia (CCCA) (12.4%) and acne keloidalis nuchae (AKN) (12.4%). The
      other subtypes include folliculitis decalvans (FD), discoid lupus erythematosus
      (DLE) and pseudopelade of Brocq (PPB). Interestingly, FD, DC and AKN were more
      common in males, while CCCA, LPP, DLE and PPB had a female predominance. The mean
      age of patients with DLE, DC and AKN were younger, while patients with CCCA, LPP,
      PPB and FD tend to be older. The pattern of hair loss was more likely to be
      unifocal-ragged border in CCCA and DLE, multifocal-interconnected in LPP and FD,
      and multifocal-separated in DC. The pathogenesis of PSA may be influenced by sex,
      age and genetic background. It is important to identify the hair loss pattern to
      differentiate the subtypes of PSA.

PMID- 29341218
TI  - Metastatic Crohn's disease in childhood: A case report.

PMID- 29341217
TI  - Acetoacetate and ethyl acetoacetate as novel inhibitors of bacterial biofilm.
AB  - : Acetoacetate (AAA) was identified as a biofilm inhibitor in a previous study,
      where the effect of 190 carbon and nitrogen sources on biofilm amounts by
      Escherichia coli O157:H7 was determined. With this study, we tested the effect of
      AAA on growth and biofilm amounts of Cronobacter sakazakii, Serratia marcescens
      and Yersinia enterocolitica. AAA reduced growth and biofilm amounts of the three
      pathogens, albeit at rather high concentrations of 10 to 35 mg ml-1 .
      Acetoacetate at a concentration of 5 mg ml-1 reduced Y. enterocolitica mRNA
      transcripts of the flagellar master regulator operon flhD, the invasion gene inv,
      and the adhesion gene yadA. Transcription of the regulator of plasmid-encoded
      virulence genes virF, the plasmid-encoded virulence gene yopQ, and ymoA were
      largely unaffected by AAA. Importantly, AAA did not cause an increase in
      transcription of any of the tested virulence genes. As a more cost efficient
      homologue of AAA, the effect of ethyl acetoacetate (EAA) was tested. EAA reduced
      growth, biofilm amounts and live bacterial cell counts up to 3 logs. IC50 values
      ranged from 0.31 mg ml-1 to 5.6 mg ml-1 . In summary, both AAA and EAA inhibit
      biofilm, but EAA appears to be more effective. SIGNIFICANCE AND IMPACT OF THE
      STUDY: Bacterial biofilms are communities of bacteria that form on surfaces and
      are extremely difficult to remove by conventional physical or chemical
      techniques, antibiotics or the human immune system. Despite advanced
      technologies, biofilm still contributes to 60 to 80% of human bacterial
      infections (NIH and CDC) and cause problems in many natural, environmental,
      bioindustrial or food processing settings. The discovery of novel substances that
      inhibit biofilm without increasing the virulence of the bacteria opens doors for
      countless applications where a reduction of biofilm is desired.

PMID- 29341219
TI  - Current knowledge of nocardiosis in teleost fish.
AB  - Nocardia sp. is the causative agent of nocardiosis, a lethal granulomatous
      disease of the skin, muscle, and various inner tissues affecting various teleost
      and shellfish. Four species of Nocardia have been isolated from diseased fish and
      shellfish, namely Nocardia asteroides, Nocardia seriolae, Nocardia salmonicida
      and Nocardia crassostreae. Therefore, in fish aquaculture, nocardiosis has caused
      severe economic losses, especially in the Asian region. Considerable research has
      been performed, since the first report of identified Nocardia sp. in fish, to
      characterize Nocardia sp. and identify rapid detection techniques, immune
      response against infection and prophylactic approaches. In this review, the
      current state of knowledge about nocardiosis in fish has been presented,
      including the pathogenesis, diagnosis, host immune response and vaccine
      development.

PMID- 29341220
TI  - Prevalence of Rhodococcus equi from the nasal cavity of 1010 apparently healthy
      horses.
AB  - BACKGROUND: Rhodococcus equi is an important cause of foal pneumonia. While its
      isolation from different sources has been widely evaluated, there is a need to
      better understand the R. equi epidemiology from samples of the nasal cavity of
      healthy horses. OBJECTIVES: To determine the prevalence of R. equi from the nasal
      cavity of healthy horses, along with its virulence profile, antimicrobial
      susceptibility and environmental variables associated. STUDY DESIGN: Cross
      sectional study. METHODS: Swabs from the nasal cavity of 1010 apparently healthy
      horses from 341 farms were submitted for bacteriological analyses. The identity
      and virulence profile of the R. equi isolates were assessed by multiplex PCR;
      antimicrobial susceptibility was determined by the disk-diffusion method. The
      occurrence of R. equi was calculated at the level of both animal and farm. The
      association of seven specific environmental factors with R. equi isolation was
      assessed using logistic regression and by a spatial scan statistical method to
      determine the presence of local clusters. RESULTS: Antimicrobial-sensitive R.
      equi was isolated from 10 (1%) of 1010 horses ranging between 3 and 29 years old.
      Ten farms (3%) had at least one positive horse. Only one R. equi isolate (10%)
      was classified as virulent. Red-Yellow Argisol (PVA/PV) soils were significantly
      associated with R. equi isolation (odds ratio (OR) 8.02; CI95% , 1.98-32.50, P =
      0.01), and areas with well-drained soil were less likely to be test positive (OR
      0.85; CI95% , 0.76-0.96, P = 0.03). MAIN LIMITATIONS: The use of culture-based
      method instead of PCR-based assay and the lack of soil sampling. CONCLUSIONS:
      Antimicrobial-sensitive R. equi may be considered a minor part of the normal
      bacterial flora in the nasal cavity of healthy and immunologically functional
      horses breeding on pasture. Further studies are warranted to determine if soils
      rich in iron and well-drained are, in fact, associated with the occurrence of R.
      equi.

PMID- 29341221
TI  - Pediatric penile porokeratosis: A case report.
AB  - We present what we believe to be the second case of pediatric penile
      porokeratosis and the youngest case reported. A 6-year-old boy presented with a
      pruritic, verrucous growth at the urethral meatus that recurred after two
      meatotomies. The diagnosis of porokeratosis was confirmed by biopsy.
      Porokeratosis should be added to the differential diagnosis of chronic
      hyperkeratotic penile lesions in children.

PMID- 29341223
TI  - Disulfide bond based polymeric drug carriers for cancer chemotherapy and relevant
      redox environments in mammals.
AB  - Increasing numbers of disulfide linkage-employing polymeric drug carriers that
      utilize the reversible peculiarity of this unique covalent bond have been
      reported. The reduction-sensitive disulfide bond is usually employed as a linkage
      between hydrophilic and hydrophobic polymers, polymers and drugs, or as cross
      linkers in polymeric drug carriers. These polymeric drug carriers are designed to
      exploit the significant redox potential difference between the reducing
      intracellular environments and relatively oxidizing extracellular spaces. In
      addition, these drug carriers can release a considerable amount of anticancer
      drug in response to the reducing environment when they reach tumor tissues,
      effectively improving antitumor efficacy. This review focuses on various
      disulfide linkage-employing polymeric drug carriers. Important redox thiol pools,
      including GSH/GSSG, Cys/CySS, and Trx1, as well as redox environments in mammals,
      will be introduced.

PMID- 29341222
TI  - 89 Zr-ImmunoPET companion diagnostics and their impact in clinical drug
      development.
AB  - Therapeutic monoclonal antibodies have been used in cancer treatment for 30
      years, with around 24 mAb and mAb:drug conjugates approved by the FDA to date.
      Despite their specificity, efficacy has remained limited, which, in part, derails
      nascent initiatives towards precision medicine. An image-guided approach to
      reinforce treatment decisions using immune positron emission tomography
      (immunoPET) companion diagnostic is warranted. This review provides a general
      overview of current translational research using Zr-89 immunoPET and
      opportunities for utilizing and harnessing this tool to its full potential.
      Patient case studies are cited to illustrate immunoPET probes as tools for
      profiling molecular signatures. Discussions on its utility in reinforcing
      clinical decisions as it relates to histopathological tumor assessment and
      standard diagnostic methods, and its potential as predictive biomarkers, are
      presented. We finally conclude with an overview of practical considerations to
      its utility in the clinic.

PMID- 29341224
TI  - Comparative RNA-Seq transcriptome analysis on silica induced pulmonary
      inflammation and fibrosis in mice silicosis model.
AB  - Silicosis is a long-established public health issue in developing countries due
      to increasingly serious air pollution and poorly implemented occupational safety
      regulation. Inhalation of silica triggers cytotoxicity, oxidative stress,
      pulmonary inflammation and eventually silicosis. Current understanding in the
      pathogenesis and mechanism of silicosis is limited, and no effective cure is
      clinically available once silicosis is developed. A number of studies were
      conducted to investigate silica-induced alternate gene expressions in pulmonary
      cells. However, transcriptome analysis in a silicosis animal model is needed.
      This study was performed to evaluate the transcriptional alternations in
      silicotic mice using comparative RNA-Seq. A silicosis mice model was established
      by intratracheal instillation of silica suspensions, and validated by
      histological examinations. High-throughput sequencing and differential gene
      expression analysis revealed 749 upregulated genes and 70 downregulated genes in
      the silicosis model. Genes related to immune cell interactions, immune cell
      responses and inflammation were significantly enriched. Cytokine-cytokine
      receptor interaction and downstream JAK-STAT signaling pathways were the most
      significantly enriched KEGG pathways. Reverse transcription-polymerase chain
      reaction analysis and immunohistochemistry were performed to validate further the
      differential expression patterns of representative genes. The reported results in
      this study provide the basis for elucidating the molecular mechanisms for silica
      induced pulmonary inflammation and fibrosis, and support the prevention and
      treatment of silicosis.

PMID- 29341225
TI  - Past and present mercury accumulation in the Lake Baikal seal: Temporal trends,
      effects of life history, and toxicological implications.
AB  - Despite global efforts to reduce anthropogenic mercury (Hg) emissions, the
      timescale and degree to which Hg concentrations in the environment and biota
      respond to decreased emissions remain challenging to assess or predict. In the
      present study we characterize long-term trends and life-history patterns in Hg
      accumulation and toxicological implications of Hg contamination for a freshwater
      seal from one of the world's largest lakes (Lake Baikal, Siberia, Russia) using
      contemporary tissues and archival teeth. Stable isotope analysis and Hg analyses
      of soft tissues (muscle, liver, kidney, blood, brain, heart) and teeth from 22
      contemporary seals revealed rapid changes in diet and Hg accumulation in the
      first year of life with a stable diet and increase in tissue Hg throughout the
      rest of life. Although maternal transfer of Hg was an important source of Hg to
      seal pups, reproduction and lactation by female seals did not appear to result in
      sex-related differences in Hg concentrations or age-related accumulation in adult
      seals. Based on Hg analysis of archival teeth (n = 114) and reconstructed values
      for soft tissues, we also assessed temporal trends in seal Hg between the years
      1960 and 2013. Seal Hg concentrations in hard (teeth) and soft (e.g., muscle,
      liver) tissues were highest in the 1960s and 1970s, followed by a decrease. The
      decline in seal Hg concentrations in recent decades was most likely driven by a
      reduction in Hg inputs to the lake, suggesting that global and regional efforts
      to reduce Hg emissions have been successful at reducing ecosystem and human
      health risks posed by Hg in Lake Baikal. Environ Toxicol Chem 2018;37:1476-1486.
      (c) 2018 SETAC.

PMID- 29341226
TI  - Molecular details of spontaneous insertion and interaction of HCV non-structure 3
      protease protein domain with PIP2-containing membrane.
AB  - Hepatitis C virus (HCV), known as the leading cause of liver cirrhosis, viral
      hepatitis, and hepatocellular carcinoma, has been affecting more than 150 million
      people globally. The HCV non-structure 3 (NS3) protease protein domain plays a
      key role in HCV replication and pathogenesis; and is currently a primary target
      for HCV antiviral therapy. Through unbiased molecular dynamics simulations which
      take advantage of the novel highly mobile membrane mimetic model, we constructed
      the membrane-bound state of the protein domain at the atomic level. Our results
      indicated that protease domain of HCV NS3 protein can spontaneously bind and
      penetrate to an endoplasmic reticulum complex membrane containing
      phosphatidylinositol 4,5-bisphosphate (PIP2). An amphipathic helix alpha0 and
      loop S1 show their anchoring role to keep the protein on the membrane surface.
      Proper orientation of the protein domain at membrane surface was identified
      through measuring tilt angles of two specific vectors, wherein residue R161 plays
      a crucial role in its final orientation. Remarkably, PIP2 molecules were observed
      to bind to three main sites of the protease domain via specific electrostatic
      contacts and hydrogen bonds. PIP2-interaction determines the protein orientation
      at the membrane while both hydrophobic interplay and PIP2-interaction can
      stabilize the NS3 - membrane complex. Simulated results provide us with a
      detailed characterization of insertion, orientation and PIP2-interaction of NS3
      protease domain at membrane environment, thus enhancing our understanding of
      structural functions and mechanism for the association of HCV non-structure 3
      protein with respect to ER membranes.

PMID- 29341228
TI  - Bronchoalveolar lavage fluid neutrophilia is associated with the severity of
      pulmonary lesions during equine asthma exacerbations.
AB  - BACKGROUND: The severe form of equine asthma is associated with pathological
      changes of the peripheral airways and pulmonary parenchyma that are only partly
      described. Also, the relationship between these structural alterations and the
      percentage of neutrophils found within the airway lumen, assessed by
      bronchoalveolar lavage fluid (BALF) cytology, remains ill-defined. OBJECTIVE: To
      examine the histological lesions associated with equine asthma during disease
      exacerbation and remission, and their relationship with lung function and BALF
      neutrophilia. STUDY DESIGN: Observational retrospective study. METHODS:
      Peripheral lung tissues, BALF cytology and lung function data from 61 horses (22
      controls, 24 asthma exacerbations and 15 asthma remission) were obtained from an
      equine pulmonary tissue bank. Two pathologists semi-quantitatively assessed
      histological features, including airway wall inflammation, interstitial fibrosis,
      mucus cell hyperplasia, mucostasis, peribronchiolar metaplasia, presence of
      granuloma and the overall severity of these lesions. RESULTS: Mucostasis, mucus
      cell hyperplasia, peribronchiolar metaplasia and interstitial fibrosis were
      associated with disease exacerbation (P<=0.05), and these changes were all
      attenuated during remission. Airway wall inflammation was greater in horses with
      asthma in exacerbation compared with horses with asthma in remission and control
      horses (P<=0.05). Acute (neutrophilic) airway wall inflammation was more
      frequently detected in asthmatic cases compared with control horses (P<0.0001)
      and was associated with BALF neutrophilia >5% in control horses (P = 0.002). The
      degree of bronchiolar inflammation was higher in asthmatic horses in remission
      stabled and treated pharmacologically compared with those kept on pasture (P =
      0.04). MAIN LIMITATIONS: Samples obtained from a convenient cohort of horses were
      studied. CONCLUSIONS: Severely asthmatic horses present parenchymal and
      peribronchial/peribronchiolar lesions possibly contributing to the obstructive
      nature of the disease.

PMID- 29341229
TI  - Assessing and mitigating simulated population-level effects of 3 herbicides to a
      threatened plant: Application of a species-specific population model of Boltonia
      decurrens.
AB  - Extrapolating from organism-level endpoints, as generated from standard pesticide
      toxicity tests, to populations is an important step in threatened and endangered
      species risk assessments. We apply a population model for a threatened herbaceous
      plant species, Boltonia decurrens, to estimate the potential population-level
      impacts of 3 herbicides. We combine conservative exposure scenarios with dose
      response relationships for growth and survival of standard test species and apply
      those in the species-specific model. Exposure profiles applied in the B.
      decurrens model were estimated using exposure modeling approaches. Spray buffer
      zones were simulated by using corresponding exposure profiles, and their
      effectiveness at mitigating simulated effects on the plant populations was
      assessed with the model. From simulated exposure effects scenarios that affect
      plant populations, the present results suggest that B. decurrens populations may
      be more sensitive to exposures from herbicide spray drift affecting vegetative
      stages than from runoff affecting early seedling survival and growth. Spray
      application buffer zones were shown to be effective at reducing effects on
      simulated populations. Our case study demonstrates how species-specific
      population models can be applied in pesticide risk assessment to bring organism
      level endpoints, exposure assumptions, and species characteristics together in an
      ecologically relevant context. Environ Toxicol Chem 2018;37:1545-1555. (c) 2018
      SETAC.

PMID- 29341227
TI  - PET radiometals for antibody labeling.
AB  - Recent advances in molecular characterization of tumors have made possible the
      emergence of new types of cancer therapies where traditional cytotoxic drugs and
      nonspecific chemotherapy can be complemented with targeted molecular therapies.
      One of the main revolutionary treatments is the use of monoclonal antibodies
      (mAbs) that selectively target the disseminated tumor cells while sparing normal
      tissues. mAbs and related therapeutics can be efficiently radiolabeled with a
      wide range of radionuclides to facilitate preclinical and clinical studies. Non
      invasive molecular imaging techniques, such as Positron Emission Tomography
      (PET), using radiolabeled mAbs provide useful information on the whole-body
      distribution of the biomolecules, which may enable patient stratification,
      diagnosis, selection of targeted therapies, evaluation of treatment response, and
      prediction of dose limiting tissue and adverse effects. In addition, when mAbs
      are labeled with therapeutic radionuclides, the combination of immunological and
      radiobiological cytotoxicity may result in enhanced treatment efficacy. The
      pharmacokinetic profile of antibodies demands the use of long half-life isotopes
      for longitudinal scrutiny of mAb biodistribution and precludes the use of well
      stablished short half-life isotopes. Herein, we review the most promising PET
      radiometals with chemical and physical characteristics that make the appealing
      for mAb labeling, highlighting those with theranostic radioisotopes.

PMID- 29341230
TI  - Successful treatment of rituximab- and steroid-resistant nephrotic syndrome with
      leukocytapheresis.
AB  - Although rituximab (RTX) is a promising therapeutic agent for treating steroid
      resistant nephrotic syndrome (SRNS) resistant to various immunosuppressive
      agents, some patients have shown resistance to RTX. We report the case of a
      patient with RTX-resistant nephrotic syndrome and SRNS who was successfully
      treated with leukocytapheresis (LCAP). After LCAP, there was a significant
      reduction in proteinuria and in the total number of lymphocytes, T cells, and HLA
      DR+- activated T cells. Moreover, the patient became sensitive to steroids and
      RTX. LCAP reduced circulating immune cells including activated T cells and could
      be effective in treating rituximab-resistant nephrotic syndrome and SRNS and in
      achieving remission of proteinuria.

PMID- 29341231
TI  - Dermoscopic features of Bednar tumor: Report of a case.

PMID- 29341232
TI  - Histological features and outcome of inverted type-A melanocytic nevi.
AB  - The presence of enlarged epithelioid/spindled nests located deep in the reticular
      dermis of a biphasic melanocytic neoplasm can mimic melanoma arising in a pre
      existing nevus, causing over-interpretation of malignancy. We aimed to define the
      clinicopathologic significance of epithelioid/spindled nests in melanocytic nevi.
      Retrospectively using clinical and histologic information, we characterized 121
      patients with a single lesion showing epithelioid/spindled melanocytes in the
      reticular dermis or subcutaneous fat, surrounded by melanophages, sometimes
      blending in with the adnexa. The majority of nevi occurred in women in the ages
      of 10 to 39 years, where the most frequent presentation was a changing mole.
      While 78% of the lesions displayed an anatomic (Clark's) level of IV-V, there was
      no ulceration, significant regression or inflammation. Up to 2 mitoses were found
      in only 12% of the cases, not correlating with the severity of cytological
      atypia. No recurrence or metastasis occurred during 45.5 months (mean) of
      clinical follow up in 26 patients. Notwithstanding the deep dermal extension,
      these findings suggest a benign histopathology and clinical outcome. Having
      compared the overlapping histopathology and clinical features between deep
      penetrating/clonal nevus and combined nevus, we posit that "inverted type-A
      nevus" might be considered a variant of the two.

PMID- 29341233
TI  - Fate, uptake, and distribution of nanoencapsulated pesticides in soil-earthworm
      systems and implications for environmental risk assessment.
AB  - Nanopesticides are novel plant protection products offering numerous benefits.
      Because nanoparticles behave differently from dissolved chemicals, the
      environmental risks of these materials could differ from conventional pesticides.
      We used soil-earthworm systems to compare the fate and uptake of analytical-grade
      bifenthrin to that of bifenthrin in traditional and nanoencapsulated
      formulations. Apparent sorption coefficients for bifenthrin were up to 3.8 times
      lower in the nano treatments than in the non-nano treatments, whereas dissipation
      half-lives of the nano treatments were up to 2 times longer. Earthworms in the
      nano treatments accumulated approximately 50% more bifenthrin than those in the
      non-nano treatments. In the non-nano treatments, most of the accumulated material
      was found in the earthworm tissue, whereas in the nano treatments, the majority
      resided in the gut. Evaluation of toxicokinetic modeling approaches showed that
      models incorporating the release rate of bifenthrin from the nanocapsule and
      distribution within the earthworm provided the best estimations of uptake from
      the nano-formulations. Overall, our findings indicate that the risks of
      nanopesticides may be different from those of conventional formulations. The
      modeling presented provides a starting point for assessing risks of these
      materials but needs to be further developed to better consider the behavior of
      the nanoencapsulated pesticide within the gut system. Environ Toxicol Chem
      2018;37:1420-1429. (c) 2018 SETAC.

PMID- 29341234
TI  - Microangiopathy and acute kidney injury in paroxysmal cold hemoglobinuria: A
      challenge for management.

PMID- 29341235
TI  - Concomitant cutaneous squamous cell carcinoma and chronic lymphocytic leukemia in
      a patient: The utility of 18 F-FDG PET/CT in differentiation of nodal metastasis.

PMID- 29341236
TI  - Induced Earthquakes from Long-Term Gas Extraction in Groningen, the Netherlands:
      Statistical Analysis and Prognosis for Acceptable-Risk Regulation.
AB  - Recently, growing earthquake activity in the northeastern Netherlands has aroused
      considerable concern among the 600,000 provincial inhabitants. There, at 3 km
      deep, the rich Groningen gas field extends over 900 km2 and still contains about
      600 of the original 2,800 billion cubic meters (bcm). Particularly after 2001,
      earthquakes have increased in number, magnitude (M, on the logarithmic Richter
      scale), and damage to numerous buildings. The man-made nature of extraction
      induced earthquakes challenges static notions of risk, complicates formal risk
      assessment, and questions familiar conceptions of acceptable risk. Here, a 26
      year set of 294 earthquakes with M >= 1.5 is statistically analyzed in relation
      to increasing cumulative gas extraction since 1963. Extrapolations from a fast
      rising trend over 2001-2013 indicate that-under "business as usual"-around 2021
      some 35 earthquakes with M >= 1.5 might occur annually, including four with M >=
      2.5 (ten-fold stronger), and one with M >= 3.5 every 2.5 years. Given this uneasy
      prospect, annual gas extraction has been reduced from 54 bcm in 2013 to 24 bcm in
      2017. This has significantly reduced earthquake activity, so far. However, when
      extraction is stabilized at 24 bcm per year for 2017-2021 (or 21.6 bcm, as
      judicially established in Nov. 2017), the annual number of earthquakes would
      gradually increase again, with an expected all-time maximum M ~ 4.5. Further
      safety management may best follow distinct stages of seismic risk generation,
      with moderation of gas extraction and massive (but late and slow) building
      reinforcement as outstanding strategies. Officially, "acceptable risk" is mainly
      approached by quantification of risk (e.g., of fatal building collapse) for
      testing against national safety standards, but actual (local) risk estimation
      remains problematic. Additionally important are societal cost-benefit analysis,
      equity considerations, and precautionary restraint. Socially and psychologically,
      deliberate attempts are made to improve risk communication, reduce public
      anxiety, and restore people's confidence in responsible experts and policymakers.

PMID- 29341238
TI  - Temporal trends in a biomagnifying contaminant: Application of amino acid
      compound-specific stable nitrogen isotope analysis to the interpretation of bird
      mercury levels.
AB  - Temporal trends in levels of biomagnifying contaminants, such as mercury (Hg), in
      top predators can provide insights into changes in contaminant bioavailability
      through time. However, interpreting contaminant temporal trends in predators can
      be confounded by temporal changes in their diets, which, in turn, could affect
      organism trophic position and exposure to biomagnifying contaminants. To address
      this issue, bulk stable nitrogen isotope analysis, that is, analysis of whole
      tissue, is widely incorporated into contaminant-monitoring programs for the
      estimation of organism trophic position. In the present study, we investigated
      lake-specific temporal trends in Hg levels in herring gull (Larus argentatus
      smithsonianus) eggs from Lakes Huron and Erie, 2 Laurentian Great Lakes. Levels
      of Hg in Lake Huron eggs declined, whereas Lake Erie eggs showed no change.
      Stable nitrogen isotope analysis of bulk material could not explain these
      interlake differences in Hg temporal trends. However, application of amino acid
      compound-specific stable nitrogen isotope analysis, in conjunction with other
      dietary tracers (i.e., fatty acids), provided insights into the factors
      regulating interlake differences in Hg temporal trends. Adjusting Hg levels in
      predators to account for temporal changes in their diets can have a significant
      impact on the interpretation of temporal trend contaminants data. In this case,
      it reconciled the apparently different Hg temporal trends observed in gull eggs
      from Lakes Huron and Erie. Environ Toxicol Chem 2018;37:1458-1465. (c) 2018
      SETAC.

PMID- 29341237
TI  - The impact of diuretic use and ABCG2 genotype on the predictive performance of a
      published allopurinol dosing tool.
AB  - AIM: This research aims to evaluate the predictive performance of a published
      allopurinol dosing tool. METHODS: Allopurinol dose predictions were compared to
      the actual dose required to achieve serum urate (SU) <0.36 mmol l-1 using mean
      prediction error. The influence of patient factors on dose predictions was
      explored using multilinear regression. RESULTS: Allopurinol doses were
      overpredicted by the dosing tool; however, this was minimal in patients without
      diuretic therapy (MPE 63 mg day-1 , 95% CI 40-87) compared to those receiving
      diuretics (MPE 295 mg day-1 , 95% CI 260-330, P < 0.0001). ABCG2 genotype
      (rs2231142, G>T) had an important impact on the dose predictions (MPE 201, 107,
      15 mg day-1 for GG, GT and TT, respectively, P < 0.0001). Diuretic use and ABCG2
      genotype explained 53% of the variability in prediction error (R2  = 0.53, P =
      0.0004). CONCLUSIONS: The dosing tool produced acceptable maintenance dose
      predictions for patients not taking diuretics. Inclusion of ABCG2 genotype and a
      revised adjustment for diuretics would further improve the performance of the
      dosing tool.

PMID- 29341239
TI  - Interaction between healthcare professionals and parents is a key determinant of
      parental distress during childhood hospitalisation for respiratory syncytial
      virus infection (European RSV Outcomes Study [EROS]).
AB  - AIM: We characterised the distress that parents experienced when their child was
      hospitalised for respiratory syncytial virus (RSV) infection. METHODS: This
      survey-based, observational study was conducted during 2014-2015. Meetings were
      held in Spain and Italy, with 24 parents of RSV hospitalised infants and 11
      healthcare professionals experienced in RSV, which identified 110 factors related
      to parental distress. The resulting questionnaire was completed by another 105
      Spanish and Italian parents and 56 healthcare professionals, to assess the impact
      these factors had on parental distress, using a scale from 0 to 10 (very
      unimportant to very important). RESULTS: The five most important factors for
      parents were: healthcare professionals' awareness of the latest developments,
      readmission, reinfections, painful procedures and positive experiences with
      healthcare professionals. Healthcare professionals associated only medical
      factors with a meaningful impact on parents. Half of the six medical factors were
      given similar importance by both groups and the overall scoring for the 110
      factors was comparable, with a correlation coefficient of 0.80. A primary concern
      on discharge was ongoing support. CONCLUSION: The relationship between parents
      and healthcare professionals was a significant factor in determining parental
      distress. Healthcare professionals appeared to have a good understanding of the
      overall impact on parents, particularly the key medical factors.

PMID- 29341240
TI  - A case report and literature review of autism and attention deficit hyperactivity
      disorder in paediatric chronic pain.
AB  - : Psychiatric disorders are common in paediatric patients with chronic pain, but
      the overall prevalence of comorbid neurodevelopmental disorders is unclear. We
      report on a case of severe chronic pain in a child with undiagnosed comorbid
      autism spectrum disorder and attention deficit hyperactivity disorder, where
      significant improvements in pain and function occurred following methylphenidate
      medication and parental behavioural training. CONCLUSION: The inclusion of
      behavioural assessment and screening for neurodevelopmental comorbidity may be
      essential in addressing complex paediatric chronic pain.

PMID- 29341241
TI  - Pan-pseudothrombocytopenia: An unusual case of platelet clumping.

PMID- 29341242
TI  - Acute generalized exanthematous pustulosis induced by a digestive enzyme drug,
      Festal(r).

PMID- 29341243
TI  - Subcutaneous basal cell carcinoma.

PMID- 29341244
TI  - Re: Challenges in research on pregnancy termination and ethical considerations.

PMID- 29341245
TI  - Pharmacokinetic/pharmacodynamic drug-drug interactions of avatrombopag when
      coadministered with dual or selective CYP2C9 and CYP3A interacting drugs.
AB  - AIMS: Avatrombopag, a thrombopoietin receptor agonist, is a substrate of
      cytochrome P450 (CYP) 2C9 and CYP3A. We assessed three drug-drug interactions of
      avatrombopag as a victim with dual or selective CYP2C9/3A inhibitors and
      inducers. METHODS: This was a three-part, open-label study. Forty-eight healthy
      subjects received single 20 mg doses of avatrombopag alone or with one of 3
      CYP2C9/3A inhibitors or inducers: fluconazole 400 mg once daily for 16 days,
      itraconazole 200 mg twice daily on Day 1 and 200 mg once daily on Days 2-16, or
      rifampicin 600 mg once daily for 16 days. Pharmacokinetics, pharmacodynamics
      (platelet count) and safety of avatrombopag were evaluated. RESULTS:
      Coadministration of a single 20-mg dose of avatrombopag with fluconazole at
      steady-state resulted in 2.16-fold increase of AUC of avatrombopag, prolonged
      terminal elimination phase half-life (from 19.7 h to 39.9 h) and led to a
      clinically significant increase in maximum platelet count (1.66-fold).
      Itraconazole had a mild increase on both avatrombopag pharmacokinetics and
      pharmacodynamics compared to fluconazole. Coadministration of rifampicin caused a
      0.5-fold decrease in AUC and shortened terminal elimination phase half-life (from
      20.3 h to 9.84 h), but has no impact on maximum platelet count. Coadministration
      with interacting drugs was found to be generally safe and well-tolerated.
      CONCLUSIONS: The results from coadministration of fluconazole or itraconazole
      suggest that CYP2C9 plays a more predominant role in metabolic clearance of
      avatrombopag than CYP3A. To achieve comparable platelet count increases when
      avatrombopag is coadministered with CYP3A and CYP2C9 inhibitors, an adjustment in
      the dose or duration of treatment is recommended, while coadministration with
      strong inducers is not currently recommended.

PMID- 29341246
TI  - Risk factors for disordered weight control behaviors among Korean adolescents:
      Multilevel analysis of the Korea Youth Risk Behavior Survey.
AB  - OBJECTIVE: To investigate the prevalence and risk factors for disordered weight
      control behaviors (DWCB) in South Korean adolescents at multiple levels,
      including individual, family, school, and geographic area. METHOD: We drew
      participants from the 11th Korea Youth Risk Behavior Web-based Survey, conducted
      in 2015, with 65,529 adolescents (31,687 girls, 33,842 boys) aged 12-18 years.
      DWCB was defined as engaging in any of the following behaviors for weight control
      over the past month: fasting, one-food diet (eating only one food over an
      extended period of time for weight control), vomiting, and taking
      laxatives/diuretics/unprescribed diet pills. Sex-stratified four-level multilevel
      logistic models examined potential predictors of DWCB, including age, body-mass
      index, puberty, perceived household economic status, parental education, living
      structure, school type and sex-composition, percentage of students participating
      in school nutrition programs, and urbanicity. RESULTS: Overall, 6.2% of Korean
      adolescents (8.9% of girls, 3.7% of boys) exhibited any DWCB. We found
      significant between-school variation among girls and boys and between-classroom
      variation among girls. Older age, overweight/obesity, pubertal maturity, high
      household economic status (vs. mid-range economic status), and vocational
      schooling (vs. general) were positively associated with DWCB among girls and
      boys. Low household economic status (vs. mid-range economic status), higher
      parental education, and coeducational schooling (vs. single-sex) were positively
      associated with DWCB among girls only. DISCUSSION: The findings suggest that DWCB
      are prevalent among Korean adolescents across age, sex, and socioeconomic status.
      Social contextual factors including school and familial environmental factors, as
      well as individual characteristics, should be considered when developing
      effective prevention strategies.

PMID- 29341248
TI  - Are kidney transplantation outcomes improved in children weighting 15 kilograms
      or less in the last decades?

PMID- 29341249
TI  - Reconstruction of an upper posterior thigh extensive defect with a free split
      anterolateral thigh (s-ALT) flap by perforator-to-perforator anastomosis: A case
      report.
AB  - The anterolateral thigh (ALT) flap is one of the most commonly used flap
      worldwide in reconstructive surgery, as both free flap and pedicled local flap.
      Here, we report the use of a free split anterolateral thigh (s-ALT) flap for
      reconstruction of a 14 cm * 16 cm soft tissue defect of the left upper posterior
      thigh region due to sarcoma resection in a patient. The ALT flap was harvested
      based on two musculocutaneous perforators from the right thigh and anastomosed to
      the contralateral descending branch of the lateral circumflex femoral artery
      (LCFA) in perforator-to-perforator manner, in order to gain more pedicle length
      and being able to cover the posterior thigh defect. The post-operative course was
      uneventful and the patient was discharged at 1 week post-operative. Eleven months
      after the operation, the aesthetic outcome was satisfactory with no functional
      deficit. Even though it requires technical skills and experience in perforator
      dissection, we believe that the s-ALT flap anstomosed to the contralateral LCFA
      in perforator to perforator fashion, may be a good solution in case of such a
      difficultly located extensive defect of the posterior thigh.

PMID- 29341247
TI  - Secretory expression of negative regulatory region of human Notch1 in Escherichia
      coli and preparation of a functional polyclonal antibody.
AB  - Notch signaling is a highly conserved pathway existed in multicellular organisms.
      It plays roles in normal human body development, human cancer initiation,
      progression and metastasis. The Notch negative regulatory region (NRR) is
      critical for Notch signaling, and cleavage at the S2 site in the NRR ultimately
      leads to the activation of Notch signaling. To study the function of human NRR1,
      we expressed the recombinant human NRR1 (rhNRR1) domain in Escherichia coli.
      After purification, rhNRR1 was obtained with approximately 94% purity according
      to SDS-PAGE analysis. Furthermore, the polyclonal anti-rhNRR1 serum raised by
      immunizing mouse with the purified rhNRR1 was able to reduce the generation of
      active form of Notch1 intracellular domain in HeLa cells, which implied the
      raised antibody could recognize and bind the natural conformation of Notch1 NRR.
      Preparation of rhNRR1 by this way is convenient, time-consuming, and could be
      used to the preparation of anti-NRR1 therapeutic antibody.

PMID- 29341250
TI  - Protectiveness of Cu water quality criteria against impairment of behavior and
      chemo/mechanosensory responses: An update.
AB  - A meta-analysis was conducted of studies that reported behavior and
      chemo/mechanosensory responses by fish, amphibians, and aquatic invertebrates in
      Cu-containing waters and also reported sufficient water chemistry for calculation
      of hardness-based and biotic ligand model (BLM)-based water quality criteria
      (WQC) for Cu. The calculated WQC concentrations were then compared with the
      corresponding 20% impairment concentrations (IC20) of Cu for those behavior and
      chemo/mechanosensory responses. The hardness-based acute and chronic WQC for Cu
      would not have been protective (i.e., the IC20 would have been lower than the
      WQC) in 33.6 and 26.2%, respectively, of the 107 combined behavior- and
      chemo/mechanosensory-response cases that also had adequate water chemistry data
      for BLM-based WQC calculations (32.7% inconclusive). In comparison, the BLM-based
      acute and chronic WQC for Cu would not have been protective in only 10.3 and
      4.7%, respectively, of the same 107 cases (29.9% inconclusive). To improve
      evaluations of regulatory effectiveness, researchers conducting aquatic Cu
      toxicity tests should measure and report complete BLM-input water chemistry and
      bracket the hardness-based and BLM-based WQC concentrations for Cu that would be
      applicable in their exposure waters. This meta-analysis demonstrates that,
      overall, the BLM-based WQC for Cu were considerably more protective than the
      hardness-based WQC for Cu against impairment of behavior and chemo/mechanosensory
      responses. Environ Toxicol Chem 2018;37:1260-1279. (c) 2018 SETAC.

PMID- 29341251
TI  - Residue packing in globular and intrinsically disordered proteins.
AB  - Intrinsically disordered proteins (IDPs)/regions do not have well-defined
      secondary and tertiary structures, however, they are functional and it is
      critical to gain a deep understanding of their residue packing. The shape
      distributions methodology, which is usually utilized in pattern recognition,
      clustering, and classification studies in computer science, may be adopted to
      study the residue packing of the proteins. In this study, shape distributions of
      the globular proteins and IDPs were obtained to shed light on the residue packing
      of their structures. The shape feature that was used is the sphericity of
      tetrahedra obtained by Delaunay Tessellation of points of Calpha coordinates.
      Then the sphericity probability distributions were compared by using Principal
      Component Analysis. This computational structural study shows that the set of
      IDPs constitute a more diverse set than the set of globular proteins in terms of
      the geometrical properties of their network structures.

PMID- 29341252
TI  - Painful procedures can affect post-natal growth and neurodevelopment in preterm
      infants.
AB  - AIM: This Italian study evaluated whether painful procedures during the first
      four weeks of life were related to subsequent weight gain, head circumference
      (HC) and neurodevelopmental outcomes in preterm infants, METHODS: We evaluated
      the number of invasive procedures that infants born at less than 32 weeks of
      gestational age (GA) underwent in the Neonatal Intensive Care Unit of Careggi
      Hospital, Florence, from January to December 2015. Weight and HC were recorded at
      birth, 36 weeks of PMA and six and 12 months of CA. Neurological outcomes were
      assessed at six and 12 months of CA using the Bayley Scales of Infant and Toddler
      Development - Third Edition. RESULTS: We studied 83 preterm infants with a GA of
      28 +/- 2 weeks and birth weight of 1098 +/- 340 g. A higher number of invasive
      painful procedures were related to a lower HC standard deviation score at 36
      weeks of PMA and six and 12 months of CA and with lower cognitive scores at six
      months. At 12 months, the relationship only remained significant for infants born
      at less than 28 weeks (p < 0.001). CONCLUSION: Invasive painful procedures
      affected regular HC growth and short-term cognitive scores in preterm infants in
      the first year of life.

PMID- 29341253
TI  - A generalized Blaschko linear congenital eruption.

PMID- 29341254
TI  - Do Cutibacterium acnes and Staphylococcus aureus define two different types of
      folliculitis?: Bacteriological study of scalp folliculitis.

PMID- 29341255
TI  - Data-assisted protein structure modeling by global optimization in CASP12.
AB  - In CASP12, 2 types of data-assisted protein structure modeling were experimented.
      Either SAXS experimental data or cross-linking experimental data was provided for
      a selected number of CASP12 targets that the CASP12 predictor could utilize for
      better protein structure modeling. We devised 2 separate energy terms for SAXS
      data and cross-linking data to drive the model structures into more native-like
      structures that satisfied the given experimental data as much as possible. In
      CASP11, we successfully performed protein structure modeling using simulated
      sparse and ambiguously assigned NOE data and/or correct residue-residue contact
      information, where the only energy term that folded the protein into its native
      structure was the term which was originated from the given experimental data.
      However, the 2 types of experimental data provided in CASP12 were far from being
      sufficient enough to fold the target protein into its native structure because
      SAXS data provides only the overall shape of the molecule and the cross-linking
      contact information provides only very low-resolution distance information. For
      this reason, we combined the SAXS or cross-linking energy term with our regular
      modeling energy function that includes both the template energy term and the de
      novo energy terms. By optimizing the newly formulated energy function, we
      obtained protein models that fit better with provided SAXS data than the X-ray
      structure of the target. However, the improvement of the model relative to the 1
      modeled without the SAXS data, was not significant. Consistent structural
      improvement was achieved by incorporating cross-linking data into the protein
      structure modeling.

PMID- 29341256
TI  - Case of classic Kaposi sarcoma of the penis successfully treated with
      radiotherapy.

PMID- 29341257
TI  - Bottom-Up Fabrication of Semiconductive Metal-Organic Framework Ultrathin Films.
AB  - Though generally considered insulating, recent progress on the discovery of
      conductive porous metal-organic frameworks (MOFs) offers new opportunities for
      their integration as electroactive components in electronic devices. Compared to
      classical semiconductors, these metal-organic hybrids combine the crystallinity
      of inorganic materials with easier chemical functionalization and processability.
      Still, future development depends on the ability to produce high-quality films
      with fine control over their orientation, crystallinity, homogeneity, and
      thickness. Here self-assembled monolayer substrate modification and bottom-up
      techniques are used to produce preferentially oriented, ultrathin, conductive
      films of Cu-CAT-1. The approach permits to fabricate and study the electrical
      response of MOF-based devices incorporating the thinnest MOF film reported thus
      far (10 nm thick).

PMID- 29341258
TI  - Utility of ultrasonography in hair-thread tourniquet syndrome.
AB  - A 2-year-old girl presented with a 2-month history of an erythematous, indurated
      plaque with well-defined borders on the third toe of the right foot. Bedside high
      resolution ultrasonography demonstrated a thickened epidermis overlying a
      hyperechoic focus within the dermis. Her clinical and sonographic presentation
      was in keeping with a foreign body causing hair-thread tourniquet syndrome. The
      foreign body was surgically extirpated without neurovascular sequelae.
      Ultrasonography expedited accurate diagnosis and is a promising adjunct to
      clinical evaluation for radiolucent foreign bodies.

PMID- 29341259
TI  - CHILD syndrome mimicking verrucous nevus in a Chinese patient responded well to
      the topical therapy of compound of simvastatin and cholesterol.
AB  - BACKGROUND: Congenital hemidysplasia with ichthyosiform erythroderma and limb
      defects (CHILD) syndrome is a rare X-linked dominant disorder characterized by
      peculiar cutaneous presentations and ipsilateral skeletal abnormalities. CHILD
      syndrome is caused by mutations in NSDHL gene, which involves in cholesterol
      synthesis. OBJECTIVES: To verify the diagnosis of CHILD syndrome and seek
      effective pathogenesis-based therapy with little side-effects. METHOD: We
      comprehensively evaluated the patient's conditions. Pathological biopsy was
      performed in the lesion location. Genetic tests and real-time quantitative PCR
      were conducted to further confirm the diagnosis. The topical application of a
      mixed lotion containing 2% simvastatin and 2% cholesterol to lesion areas based
      on the pathogenesis as well as the literature review. RESULTS: We diagnosed a
      rare and typical case of CHILD syndrome co-occurring with multiple VX-like
      lesions. The gene mutation is a large deletion of exon 3 and 4 of the NSDHL gene,
      which was discovered and reported for the first time in CHILD syndrome. The skin
      lesions, including the verruciform plaques and VX-like lesions, improved
      obviously after treatment. CONCLUSIONS: Multiple exons deletions or microdeletion
      was not rare in CHILD syndrome. Classical Sanger sequencing may not be useful
      enough to find all kinds of mutations. Next-generation sequencing may be more
      effective. It is important to conduct genetic counselling to prevent more serious
      defects in descendants. The excellent therapeutic effect on CHILD syndrome
      resulted from the topical treatment with simvastatin/cholesterol provides a proof
      of-concept for other topical pathogenesis-based therapies for skin disease.

PMID- 29341260
TI  - Essential oils improved weight gain, growth and feed efficiency of young dairy
      calves fed 18 or 20% crude protein starter diets.
AB  - The objective was to evaluate interactions between starter protein (180 vs. 200
      g/kg, DM basis) and a mixture of essential oils (EOs; containing thymol, eugenol,
      vanillin, limonene and guaiacol) on growth, metabolic and ruminal functions of
      Holstein dairy calves. In a completely randomized 2 * 2 factorial design, 48
      calves, 3 days old (averaging BW 42.7 +/- 1.9 kg), were allocated into groups fed
      the following diets: (i) 180 g/kg CP with no EO (180P-NEO); (ii) 180 g/kg CP with
      EO (180P-EO); (iii) 200 g/kg CP with no EO (200P-NEO); and (iv) 200 g/kg CP with
      EO (200P-EO). The EO was supplemented as 1 g/kg of starter DM. Calves were fed ad
      libitum starter diet and were weaned at day 59 of age, but diets continued until
      day 80. There were no interactive effects of CP and EO on intake and growth. Pre
      weaning feed efficiency tended to be increased for 200P-EO (p = .09). Average
      daily gain and feed efficiency during pre-weaning period as well as weaning
      weight were increased (p < .05) by EO, whereas wither height was increased by EO
      (p = .03) and tended to be increased for 200P vs. 180P (p = .06). Post-weaning
      blood urea nitrogen concentration tended to be lower in 180P vs. 200P (p = .08).
      Ruminal short-chain fatty acids concentration was greatest in 200P-EO. The EO
      increased both butyrate (p = .02) and propionate proportions (p = .01) and
      reduced acetate proportional ratio (p < .01). Ruminal ammonia-N was tended to be
      lower in calves-fed EO (p = .05) and was lower in those fed 180P vs. 200P (p <
      .01). In conclusion, supplementation of the starter diet with essential oil
      improved weight gain, growth and feed efficiency of dairy calves, irrespective of
      dietary protein content.

PMID- 29341261
TI  - Consensus statements on the clinical understanding and use of milnacipran in Hong
      Kong.
AB  - OBJECTIVE: Our aim is to develop a local consensus to guide medical practitioners
      and psychiatrists on the use of milnacipran in different psychiatric conditions.
      METHODS: By utilizing the modified Delphi technique, 12 statements were
      electronically voted on anonymously for their practicability of recommendation.
      RESULTS: There was a very high degree of agreement among the consensus group on
      10 finalized consensus statements, but 2 statements were voted down due to a poor
      degree of agreement. CONCLUSIONS: The present consensus statements were developed
      as general recommendations for medical practitioners and psychiatrists to be
      practically referred to in clinical settings.

PMID- 29341262
TI  - Reversine inhibits MMP-1 and MMP-3 expressions by suppressing of ROS/MAPK/AP-1
      activation in UV-stimulated human keratinocytes and dermal fibroblasts.
AB  - UVB has been shown to stimulate the generation of reactive oxygen species (ROS),
      which subsequently results in the activation of various intracellular signalling
      pathways and transcription factors (AP-1, NF-kappaB). These transcription factors
      are regulated by MAPKs, which increase cytokine and MMP expression. We examined
      the preventive effects of reversine on MMP-1 and MMP-3 expressions in NHEKs and
      NHDFs exposed to UVB irradiation. Also, we confirmed that reversine decreased pro
      inflammatory cytokine expression in NHEKs. The mechanism underlying the MMP
      inhibitory effects of reversine occurred via the suppression of UVB-induced ROS
      generation and MAPK/AP-1 activation. Therefore, reversine is an effective
      therapeutic candidate for preventing skin photoageing.

PMID- 29341264
TI  - A Facile Method to Fabricate Anisotropic Hydrogels with Perfectly Aligned
      Hierarchical Fibrous Structures.
AB  - Natural structural materials (such as tendons and ligaments) are comprised of
      multiscale hierarchical architectures, with dimensions ranging from nano- to
      macroscale, which are difficult to mimic synthetically. Here a bioinspired,
      facile method to fabricate anisotropic hydrogels with perfectly aligned
      multiscale hierarchical fibrous structures similar to those of tendons and
      ligaments is reported. The method includes drying a diluted physical hydrogel in
      air by confining its length direction. During this process, sufficiently high
      tensile stress is built along the length direction to align the polymer chains
      and multiscale fibrous structures (from nano- to submicro- to microscale) are
      spontaneously formed in the bulk material, which are well-retained in the
      reswollen gel. The method is useful for relatively rigid polymers (such as
      alginate and cellulose), which are susceptible to mechanical signal. By
      controlling the drying with or without prestretching, the degree of alignment,
      size of superstructures, and the strength of supramolecular interactions can be
      tuned, which sensitively influence the strength and toughness of the hydrogels.
      The mechanical properties are comparable with those of natural ligaments. This
      study provides a general strategy for designing hydrogels with highly ordered
      hierarchical structures, which opens routes for the development of many
      functional biomimetic materials for biomedical applications.

PMID- 29341263
TI  - Dermoscopy vs. reflectance confocal microscopy for the diagnosis of lentigo
      maligna.
AB  - BACKGROUND: Several dermoscopic and in vivo reflectance confocal microscopy (RCM)
      diagnostic criteria of lentigo maligna (LM)/lentigo maligna melanoma (LMM) have
      been identified. However, no study compared the diagnostic accuracy of these
      techniques. OBJECTIVE: We evaluated the diagnostic accuracy of dermoscopy and RCM
      for LM/LMM using a holistic assessment of the images. METHODS: A total of 223
      facial lesions were evaluated by 21 experts. Diagnostic accuracy of the clinical,
      dermoscopic and RCM examination was compared. Interinvestigator variability and
      confidence level in the diagnosis were also evaluated. RESULTS: Overall
      diagnostic accuracy of the two imaging techniques was good (area under the curve
      of the sROC function: 0.89). RCM was more sensitive (80%, vs. 61%) and less
      specific (81% vs. 92%) than dermoscopy for LM/LMM. In particular, RCM showed a
      higher sensitivity for hypomelanotic and recurrent LM/LMM. RCM had a higher
      interinvestigator agreement and a higher confidence level in the diagnosis than
      dermoscopy. CONCLUSION: Reflectance confocal microscopy and dermoscopy are both
      useful techniques for the diagnosis of facial lesions and in particular LM/LMM.
      RCM is particularly suitable for the identification of hypomelanotic and
      recurrent LM/LMM.

PMID- 29341265
TI  - Cicatricial Alopecia Research Foundation meeting, May 2016: Progress towards the
      diagnosis, treatment and cure of primary cicatricial alopecias.
AB  - Primary cicatricial alopecias (PCAs) are a group of skin diseases in which there
      is progressive and permanent destruction of hair follicles followed by
      replacement with fibrous tissue. Unfortunately, by the time patients seek
      clinical evaluation of their hair loss, the skin is already inflamed and/or
      scarred, so there is little hope for a return to their normal hair growth
      pattern. Clinical and basic science investigations are now focusing on three
      forms of human PCA: lichen planopilaris (LPP), frontal fibrosing alopecia (FFA)
      and central centrifugal cicatricial alopecia (CCCA). Transcriptome, lipidome and
      other new technologies are providing new insight into the pathogenesis of some of
      these diseases that are being validated and further investigated using
      spontaneous and genetically engineered mouse models.

PMID- 29341266
TI  - Merkel cell carcinoma in France: a registries-based, comprehensive
      epidemiological survey.
AB  - BACKGROUND: Merkel cell carcinoma (MCC) is a rare primary cutaneous
      neuroendocrine carcinoma. Owing to its low incidence, epidemiological data are
      scarce and have never been analysed in France to identify the main
      epidemiological trends. METHODS: Data from MCC patients diagnosed between 1998
      and 2010 were obtained from 11 French cancer registries in the FRANCIM network.
      The main epidemiological characteristics of MCC were investigated between 2006
      and 2010 because comprehensive data were only available for this period. The main
      focus was tumour incidence and mortality over time. RESULTS: Between 1998 and
      2010, 562 cases of MCC were reported in the registries. From 2006 to 2010 (290
      cases), European- and world-standardized incidence rates were 0.26 and 0.43 per
      100,000 person-years in men and 0.24 and 0.38 per 100,000 person-years in women.
      MCC is more frequent in females in France (56.9%) with male/female ratio 1.1.
      Relative survival rates were 84%, 56% and 42% at one, three and 5 years,
      respectively. CONCLUSIONS: The incidence of MCC clearly increased over time in
      all areas under focus. The standardized incidence in France was comparable to the
      incidence observed in other countries for the same period, but French data are
      too recent to conclude on an increase in MCC incidence. Prognosis remains poor in
      all countries in which data are available.

PMID- 29341267
TI  - Cross-Linking of Thiolated Paclitaxel-Oligo(p-phenylene vinylene) Conjugates
      Aggregates inside Tumor Cells Leads to "Chemical Locks" That Increase Drug
      Efficacy.
AB  - How to reduce the resistance of certain tumor cells to paclitaxel (PTX) and
      related taxoid anticancer drugs is a major challenge for improving cure rates. An
      oligo(p-phenylenevinylene) unit with thiol groups and a PTX unit (OPV-S-PTX),
      which enhances drug efficacy and reverses resistance is thus designed. The
      mechanism involves diffusion of OPV-S-PTX into the cell, where pi-pi interactions
      lead to aggregation. Cross-linking of the aggregates via oxidation of thiol
      groups is favored in tumor cells because of the higher reactive oxygen species
      (ROS) concentration. Cross-linked aggregates "chemically lock" the
      multichromophore particle for a more persistent effect. The IC50 of OPV-S-PTX for
      tumor cell line A549 is reduced down to 0.33 * 10-9 m from that observed for PTX
      itself (41 * 10-9 m). Enhanced efficacy by OPV-S-PTX is proposed to proceed via
      acceleration of microtubule bundle formation. A549/T-inoculated xenograft mice
      experiments reveal suppression of tumor growth upon OPV-S-PTX treatment.
      Altogether, these results show that the internal cross-linking of OPV-S-PTX
      through ROS provides a means to discriminate between tumor and healthy cells and
      the formation of the chemically locked particles enhances drug efficacy and helps
      in reducing resistance.

PMID- 29341268
TI  - Evans syndrome secondary to undiagnosed chronic lymphocytic leukemia in a patient
      with unexplained bleeding.

PMID- 29341271
TI  - Review shows that early foetal alcohol exposure may cause adverse effects even
      when the mother consumes low levels.
AB  - AIM: Studies are increasingly focusing on the effects of prenatal alcohol
      exposure (PAE) on child health. The aim of this review was to provide
      paediatricians with new insights to help them communicate key messages about
      avoiding alcohol during pregnancy. METHODS: Inspired by the 7th International
      Conference on Fetal Alcohol Spectrum Disorder, which focused on integrating
      research, policy and practice, we studied English language papers published since
      2010 on how early PAE triggered epigenetic mechanisms that had an impact on the
      development of some chronic diseases. We also report the findings of a human
      study using three-dimensional photography of the face to explore associations
      between PAE and craniofacial phenotyping. RESULTS: Animal models with different
      alcohol exposure patterns show that early PAE may lead to long-term chronic
      effects, due to developmental programming for some adult diseases in
      cardiovascular, metabolic and renal systems. The study with three-dimensional
      photographing is very promising in helping paediatricians to understand how even
      small amounts of PAE can affect craniofacial phenotyping. CONCLUSION: Even low
      levels of PAE can cause adverse foetal effects and not just in the brain. It is
      not currently possible to determine a safe period and level when alcohol
      consumption would not affect the foetus.

PMID- 29341270
TI  - Pretransplant depression in lung recipients - a lost battle?

PMID- 29341272
TI  - Editorial: getting bullish about portal hypertension-chronic treatment with oral
      taurine?

PMID- 29341269
TI  - Characterization of a 3xTg-AD mouse model of Alzheimer's disease with the
      senescence accelerated mouse prone 8 (SAMP8) background.
AB  - No model fully recapitulates the neuropathology of Alzheimer's disease (AD).
      Although the triple-transgenic mouse model of AD (3xTg-AD) expresses Abeta
      plaques and tau-laden neurofibrillary tangles, as well as synaptic and behavioral
      deficits, it does not display frank neuronal loss. Because old age is the most
      important risk factor in AD, senescence-related interactions might be lacking to
      truly establish an AD-like environment. To investigate this hypothesis, we bred
      the 3xTg-AD mouse with the senescence-accelerated mouse prone 8 (SAMP8), a model
      of accelerated aging. We generated four groups of heterozygous mice with either
      the SAMP8 or SAMR1 (senescence-resistant-1) genotype, along with either the 3xTg
      AD or non-transgenic (NonTg) genotype. Despite no differences among groups in
      total latency to escape the Barnes maze, a greater number of errors were noticed
      before entering the target hole in 19-month-old P8/3xTg-AD mice at day 5,
      compared to other groups. Postmortem analyses revealed increased cortical levels
      of phospho-tau (Thr231) in female P8/3xTg-AD mice (+277% vs. R1/3xTg-AD mice),
      without other tau-related changes. Female P8/3xTg-AD mice exhibited higher
      cortical soluble Abeta40 and Abeta42 concentrations (Abeta40, +85%; Abeta42, +35%
      vs. R1/3xTg-AD), whereas insoluble forms remained unchanged. Higher Abeta42 load
      coincided with increased astroglial activation in female P8/3xTg-AD mice, as
      measured with glial fibrillary acidic protein (GFAP) (+57% vs. R1/3xTg-AD mice).
      To probe neuronal degeneration, concentrations of neuronal nuclei (NeuN) were
      measured, but no differences were detected between groups. Altogether, the SAMP8
      genotype had deleterious effects on spatial memory and exerted female-specific
      aggravation of AD neuropathology without overt neurodegeneration in 3xTg-AD mice.

PMID- 29341273
TI  - Editorial: getting bullish about portal hypertension-chronic treatment with oral
      taurine? Author's reply.

PMID- 29341274
TI  - Letter: addition of azathioprine to infliximab maintenance therapy in patients
      with anti-drug antibodies and subclinical inflammation.

PMID- 29341275
TI  - Editorial: vedolizumab as a treatment and cause of extra-intestinal
      manifestations of inflammatory bowel disease.

PMID- 29341276
TI  - Letter: more studies are needed to elucidate the impact of HBV/HCV coinfection on
      cirrhosis and its consequences-Authors' reply.

PMID- 29341277
TI  - Editorial: tofacitinib and biologics for moderate-to-severe ulcerative colitis
      what is best in class? Authors' reply.

PMID- 29341278
TI  - Editorial: direct-acting antivirals significantly improve quality of life in
      patients with hepatitis C virus infection-Author's reply.

PMID- 29341279
TI  - Letter: more studies are needed to elucidate the impact of HBV/HCV coinfection on
      cirrhosis and its consequences.

PMID- 29341280
TI  - Editorial: direct-acting antivirals significantly improve quality of life in
      patients with hepatitis C virus infection.

PMID- 29341281
TI  - Editorial: tofacitinib and biologics for moderate-to-severe ulcerative colitis
      what is best in class?

PMID- 29341282
TI  - Expression analyses of candidate genes related to meat quality traits in squabs
      from two breeds of meat-type pigeon.
AB  - In this study, meat quality traits were compared between squabs from two pigeon
      breeds: one Chinese indigenous breed, the Shiqi (SQ) meat-type pigeon, and an
      imported breed, the white king (WK) meat-type pigeon. Breed differences were
      detected in the content of intramuscular fat (IMF) in the breast muscle. SQ
      squabs had significantly higher IMF content than the WK birds. The shear force
      value (an objective measure of meat tenderness) of SQ birds was also relatively
      lower than that of the WK squabs. Further analysis of fatty acids profile
      revealed that SQ squabs exhibited significant advantage in the synthesis of
      polyunsaturated fatty acids, while WK squabs were significantly higher in the sum
      of monounsaturated fatty acids. Breast muscle in the SQ squabs was also
      significantly higher in the ratio of polyunsaturated fatty acids to saturated
      fatty acids, as well as the sum of omega 6 fatty acids. Variability of expression
      levels of functional genes in relation to fat accumulation and meat tenderness
      was analysed by qRT-PCR. Gene expression analyses showed that the hepatic
      expression of LPL (lipoprotein lipase), FABP4 (fatty acid-binding protein 4), and
      CAPN2 (calpain-2) were significantly higher in the SQ squabs. In the breast
      muscle tissue, the FABP3 (fatty acid-binding protein 3) and CAPN2mRNA abundance
      was significantly higher in SQ squabs. Our results suggested that these
      differentially expressed genes might be candidate genes used in the programmes of
      targeted selection for squabs with higher IMF content, tender meat, and more
      favourable fatty acids composition.

PMID- 29341283
TI  - Mogamulizumab-induced photosensitivity in patients with mycosis fungoides and
      other T-cell neoplasms.
AB  - BACKGROUND: Mogamulizumab (Mog) is a defucosylated, therapeutic monoclonal
      antibody, targeting CCR4 and was first approved in Japan for the treatment of
      adult T-cell leukaemia/lymphoma (ATLL), followed by cutaneous T-cell lymphoma and
      peripheral T-cell lymphoma. OBJECTIVE: To retrospectively investigate development
      of photosensitivity in patients with mycosis fungoides and other T-cell neoplasms
      after treatment with Mog. METHODS: We treated seven cutaneous lymphoma patients
      with Mog. Upon combination treatment with narrow-band UVB, we noticed that four
      patients developed photosensitivity dermatitis following Mog therapy, including
      two cases of mycosis fungoides, one case of adult T-cell leukaemia/lymphoma and
      one case of EB virus-associated T-cell lymphoproliferative disorder. Phototest
      was performed with UVA and UVB, and immunohistochemical staining for CD4, CD8 and
      Foxp3 was conducted in both photosensitivity and lymphoma lesions. RESULTS:
      Phototest revealed that the action spectrum of the photosensitivity was UVB in
      three cases and both UVB and UVA in one case. Histopathologically, the
      photosensitive lesions were characterized by a lichenoid tissue reaction with a
      CD8+ T cell-dominant infiltrate, sharing the feature with chronic actinic
      dermatitis, an autoreactive photodermatosis with a cytotoxic T-cell response.
      Foxp3+ regulatory T cells (Tregs) were decreased in the photosensitivity lesions
      compared with the lymphoma lesions. CONCLUSION: Increased incidence of
      photosensitivity reaction was observed during Mog treatment. Decreased number of
      Tregs in the lesional skin suggests that this reaction is possibly induced by
      autoreactive cytotoxic T cells.

PMID- 29341284
TI  - Atypical presentation of eosinophilic annular erythema in a 5-year-old girl.

PMID- 29341285
TI  - 2,2'-Bipyridine Equipped with a Disulfide/Dithiol Switch for Coupled Two-Electron
      and Two-Proton Transfer.
AB  - [1,2]Dithiino[4,3-b:5,6-b']dipyridine (1) and its protonated open form 3,3'
      dithiol-2,2'-bipyridine (2) were synthesised and their interconversion
      investigated. The X-ray structure of 2 revealed an anti orientation of the two
      pyridine units and a zwitterionic form. In depth electrochemical studies in
      combination with DFT calculations lead to a comprehensive picture of the redox
      chemistry of 1 in the absence and presence of protons. Initial one-electron
      reduction at E1 =-1.20 V results in the formation of the radical anion 1red with
      much elongated S-S bond, which readily undergoes further reduction at E2 =-1.38
      V. Water triggers a potential inversion (E>=-1.13 V for the second reduction) as
      the radical anion 1red is protonated at its basic N atom. DFT studies revealed
      that S-S bond breaking and twisting of the pyridine units generally occurs after
      the second reduction step, whereas the potential inversion induced by protonation
      is a result of charge compensation. The CV data were simulated to derive rate
      constants for the individual chemical and electrochemical reactions for both
      scenarios in the absence and presence of protons.

PMID- 29341286
TI  - Test-1 analyzer and conventional Westergren method for erythrocyte sedimentation
      rate: A comparative study between two laboratories.
AB  - BACKGROUND: Measurement of the length of sedimentation reaction in blood (LSRB),
      also called erythrocyte sedimentation rate (ESR), is a widely used hematology
      test. This study intends to compare ESR levels measured by Test-1 method and
      International Council for Standardization in Hematology's (ICSH) reference
      method, and analyzes the effect of hematocrit (Hct) on ESR results. MATERIAL AND
      METHODS: A total of 755 patients from 2 hospitals were included in the study, and
      samples with EDTA were studied by Test-1 method for ESR measurement and total
      blood count, whereas citrated samples were studied with reference Westergren
      method. Then, 2 methods were compared. Distribution of ESR results according to
      the ESR(<=20, >20 mm/h) and Hct(>=35%, <35%) levels and hospital type was
      analyzed. ESR levels with Hct levels<35% were corrected with Fabry's formula.
      RESULTS: The mean and SD values for the Test-1 method, reference Westergren
      method, and corrected ESR measurement were 21.30 +/- 18.39, 28.59 +/- 25.82, and
      24.92 +/- 20.58 mm/h, respectively. Within the whole group, the correlation
      coefficient (r) was .77 (.7-.80) with a significance level P < .001. Passing
      Bablok regression analysis of the methods resulted in a regression equation y =
      1.00 (95% Cl: 0.43-1.88) + 0.75 (95% Cl: 0.70-0.78)x while the significance of
      linearity was acceptable (P < .01). All subgroup linear regression analyses
      revealed that the correlation was acceptable, except ESR > 20 mm/h group, Hct <
      35% group, and corrected ESR group (significance level were P > .10). CONCLUSION:
      The study showed that the role of the hospital and the capacity of testing are
      important in choosing the instrument for measuring ESR. Furthermore, the patient
      profile, especially malignancy possibility and Hct level, may be important for
      instrument selection.

PMID- 29341287
TI  - One-Pot Synthesis of Functionalized Fused Furans via a BODIPY-Catalyzed Domino
      Photooxygenation.
AB  - Six-membered ring fused furans containing a tetrasubstituted tertiary carbon were
      prepared in an unprecedented one-pot BODIPY-catalyzed domino
      photooxygenation/reduction process. A series of functionalized furans was
      synthesized from readily available 2-alkenylphenols and mechanistic studies were
      performed to account for the domino photosensitized oxygenation.

PMID- 29341288
TI  - Lipid and Nucleic Acid Chemistries: Combining the Best of Both Worlds to
      Construct Advanced Biomaterials.
AB  - Hybrid synthetic amphiphilic biomolecules are emerging as promising
      supramolecular materials for biomedical and technological applications. Herein,
      recent progress in the field of nucleic acid based lipids is highlighted with an
      emphasis on their molecular design, synthesis, supramolecular properties,
      physicochemical behaviors, and applications in the field of health science and
      technology. In the first section, the design and the study of nucleolipids are in
      focus and then the glyconucleolipid family is discussed. In the last section,
      recent contributions of responsive materials involving nucleolipids and their use
      as smart drug delivery systems are discussed. The supramolecular materials
      generated by nucleic acid based lipids open new challenges for biomedical
      applications, including the fields of medicinal chemistry, biosensors,
      biomaterials for tissue engineering, drug delivery, and the decontamination of
      nanoparticles.

PMID- 29341289
TI  - Medically unexplained dermatologic symptoms: hiding in plain sight?

PMID- 29341290
TI  - Early failure of kidney transplants in the current era-a national cohort study.
AB  - Although short-term outcome after kidney transplantation has improved, a small
      proportion of grafts are lost during the first year. We characterize in detail
      all early graft losses in the current era in a nationwide cohort of kidney
      transplant recipients. Altogether 2447 kidney transplantations, performed between
      June 2004 and October 2016, were included. All graft losses (return to dialysis
      or patient death) occurring during the first post-transplant year were
      characterized. During the first post-tranplant year, altogether 109 grafts were
      lost, 67 grafts failed, and 42 patients died. Fifty-five per cent of the deaths
      were due to cardiovascular causes, and 29% due to infectious causes. Twenty-one
      per cent of the failed grafts were primary nonfunction of unknown reason, 34%
      were lost due to venous thrombosis and 9% due to arterial thrombosis, but only 10
      (15%) patients lost a graft due to acute cellular or humoral rejection.
      Independent risk factors for death included diabetes, and longer duration of
      pretransplant dialysis treatment, whereas risk factors for graft failure included
      increased level of panel-reactive antibodies and increased cold ischaemia time.
      Kidney allografts are rarely lost due to immunological reasons during the first
      post-transplant year. The most common causes of early death after transplantation
      are cardiovascular and infectious causes.

PMID- 29341291
TI  - Dermoscopy of basal cell carcinoma.
AB  - Dermoscopy is widely used in dermatological practice. The method increases the
      accuracy of basal cell carcinoma (BCC) detection. Pigmented and nonpigmented
      variants of basal cell carcinoma present different dermoscopic features. Specific
      dermoscopy criteria have been recognized in different subtypes of BCC.
      Differentiation of superficial BCC from other subtypes is the most important
      issue, as it may determine further management decisions.

PMID- 29341292
TI  - Amniotic fluid stem cell exosomes: Therapeutic perspective.
AB  - It is widely accepted that the therapeutic potential of stem cells can be largely
      mediated by paracrine factors, also included into exosomes. Thus, stem cell
      derived exosomes represent a major therapeutic option in regenerative medicine
      avoiding, if compared to stem cells graft, abnormal differentiation and tumor
      formation. Exosomes derived from mesenchymal stem cells (MSC) induce damaged
      tissue repair, and can also exert immunomodulatory effects on the
      differentiation, activation and function of different lymphocytes. Therefore, MSC
      exosomes can be considered as a potential treatment for inflammatory diseases and
      also an ideal candidate for allogeneic therapy due to their low immunogenicity.
      Amniotic fluid stem cells (AFSCs) are broadly multipotent, can be expanded in
      culture, and can be easily cryopreserved in cellular banks. In this study,
      morphology, phenotype, and protein content of exosomes released into amniotic
      fluid in vivo and from AFSC during in vitro culture (conditioned medium) were
      examined. We found that AFSC-derived exosomes present different molecules than
      amniotic fluid ones, some of them involved in immunomodulation, such transforming
      growth factor beta and hepatic growth factors. The immunomodulatory effect of
      AFSC's exosomes on peripheral blood mononuclear cells stimulated with
      phytohemagglutinin was compared to that of the supernatant produced by such
      conditioned media deprived of exosomes. We present evidence that the principal
      effect of AFSC conditioned media (without exosomes) is the induction of apoptosis
      in lymphocytes, whereas exposure to AFSC-derived exosomes decreases the
      lymphocyte's proliferation, supporting the hypothesis that the entire secretome
      of stem cells differently affects immune-response. (c) 2017 BioFactors, 44(2):158
      167, 2018.

PMID- 29341293
TI  - Circularly Polarized Luminescence from Inorganic Materials: Encapsulating Guest
      Lanthanide Oxides in Chiral Silica Hosts.
AB  - Recently, circularly polarized luminescence (CPL)-active systems have become a
      very hot and interesting subject in chirality- and optics-related areas. The CPL
      active systems are usually available by two approaches: covalently combining a
      luminescent centre to chiral motif or associating the guest of luminescent probe
      to a chiral host. However, all the chiral components in CPL materials were
      organic, although the luminescent components were alternatively organics or
      inorganics. Herein, the first totally inorganic CPL-active system by "luminescent
      guest-chiral host" strategy is proposed. Luminescent sub-10 nm lanthanide oxides
      (Eu2 O3 or Tb2 O3 ) nanoparticles (guests) were encapsulated into chiral non
      helical SiO2 nanofibres (host) through calcination of chiral SiO2 hybrid
      nanofibres, trapping Eu3+ (or Tb3+ ). These lanthanide oxides display circular
      dichroism (CD) optical activity in the ultraviolet wavelength and CPL signals
      around at 615 nm for Eu3+ and 545 nm for Tb3+ . This work has implications for
      inorganic-based CPL-active systems by incorporation of various luminescent guests
      within chiral inorganic hosts.

PMID- 29341294
TI  - Topical nitroglycerin for the treatment of intraoperative microsurgical
      vasospasm.
AB  - BACKGROUND: Papaverine remains a popular agent to treat intraoperative
      microsurgical vasospasm. However, the recent shortage has forced surgeons to
      trial antispasmodic agents unproven in microsurgery, but commonly used in other
      areas. During this shortage we have trialed topical nitroglycerin to break
      intraoperative vasospasm. This study aims to analyze the outcomes of this
      medication on flap complications compared with papaverine. METHODS: All
      consecutive free flaps performed for breast reconstruction at a single
      institution were reviewed. Data collected included patient demographics, co
      morbidities, complications and type of antispasmodic agent. Rates of re
      exploration, complications and flap salvage were compared between patients
      receiving nitroglycerin and papaverine. RESULTS: Over 10 years, 991 flaps were
      treated with antispasmodics: 18 of which were treated with topical nitroglycerin.
      Patients treated with nitroglycerin tended to have higher BMI (32.1 vs. 27.9, P <
      0.01), higher rates of pre-operative chemotherapy (83.3% vs. 51.3%, P < 0.01) and
      shorter follow-up duration (735 vs. 1691 days, P < 0.01). However, no differences
      in complications were observed, including: unplanned return to the operating
      room, flap loss, fat necrosis, infection, hematoma, or seroma. Subgroup analysis
      with a time-matched cohort of papaverine patients revealed minimal difference in
      comorbidities and no difference in complications. CONCLUSIONS: Substituting
      topical nitroglycerin for papaverine to treat vasospasm during the shortage did
      not demonstrate an increased rate of flap loss or return to the operating room,
      making these medications a safe alternative to papaverine.

PMID- 29341295
TI  - Sustainability of the Australian radiation oncology workforce: A survey of
      radiation therapists and radiation oncology medical physicists.
AB  - This study aimed to determine and compare Radiation Therapists' (RTs') and
      Radiation Oncology Medical Physicists' (ROMPs') perspectives about their
      profession and workplace, satisfaction with career progression opportunities, and
      leaving the current workplace. RTs and ROMPs who were currently or had previously
      worked in Australia were invited to complete an online survey. Univariate and
      multivariate methods were used for analysis. Participants were 342 RTs and 112
      ROMPs with estimated response rates of 14% and 26% respectively. Both professions
      rated workload poorly and identified the need for improvement in: communication
      between professions' members, support for junior staff/new graduates, staff
      morale, on-site training and multidisciplinary communication. RTs, more than
      ROMPs, perceived their profession was recognised and respected, but RTs were less
      likely to be satisfied with career progression/advancement, job promotion
      prospects and opportunities to specialise. At least 20% of RTs and ROMPs were
      thinking about leaving their workplace and 13% of RTs and 8% of ROMPs were
      thinking about leaving their profession. Different factors contributed to
      workforce satisfaction and retention within each profession. Staff satisfaction
      and career progression are critical to retain RTs and ROMPs. Further research is
      required to explore strategies to address workplace dissatisfaction, recruitment
      and retention.

PMID- 29341296
TI  - The five-year survival of children with Down syndrome in Norway 1994-2009
      differed by associated congenital heart defects and extracardiac malformations.
AB  - AIM: We investigated the prevalence of Down syndrome in a nationwide birth
      cohort, focusing on congenital heart defects (CHDs), their associations with
      extracardiac malformations (ECM) and survival. METHODS: National registers were
      used to identify Norwegian births (1994-2009) and deaths (1994-2014) and updated
      with hospital diagnoses. We estimated birth defect frequencies in Down syndrome
      and the general population, the association between CHDs and ECM and hazard
      ratios for death from different combinations of CHDs and ECM. RESULTS: Down
      syndrome was found in 1672 of 953 450 births (17.6 per 10 000). Of the 1251 live
      births (13.3 per 10 000), 58% had CHD and 9% ECM. CHDs were associated with
      oesophageal atresia (p = 0.02) and Hirschsprung's disease (p = 0.03) but with no
      other malformations. The five-year survival for Down syndrome increased from
      91.8% (1994-1999) to 95.8% (2000-2009) (p = 0.006), and overall survival was
      92.0% with CHD and 97.4% without. Compared with Down syndrome children without
      CHD or ECM, the five-year mortality was similar for those with nonsevere CHDs,
      without or with ECM, but 4-7 times higher in those with severe CHDs without ECM
      and 13-28 times higher in those with severe CHDs and ECM. CONCLUSION: Down
      syndrome childhood survival improved, but mortality remained high with severe
      CHDs and extracardiac defects.

PMID- 29341297
TI  - Ligand- and Metal-Based Reactivity of a Neutral Ruthenium Diolefin Diazadiene
      Complex: The Innocent, the Guilty and the Suspicious.
AB  - Coordination of the diazadiene diolefin ligand (trop2 dad) to ruthenium leads to
      various complexes of composition [Ru(trop2 dad)(L)]. DFT studies indicate that
      the closed-shell singlet (CSS), open-shell singlet (OSS), and triplet electronic
      structures of this species are close in energy, with the OSS spin configuration
      being the lowest in energy for all tested functionals. Singlet-state CASSCF
      calculations revealed a significant multireference character for these complexes.
      The closed-shell singlet wavefunction dominates, but these complexes have a
      significant (~8-16 %) open-shell singlet [d7 -RuI (L)(trop2 dad.- )] contribution
      mixed into the ground state. In agreement with their ambivalent electronic
      structure, these complexes reveal both metal- and ligand-centered reactivity.
      Most notable are the reactions with AdN3 , diazomethane, and a phosphaalkyne
      leading to scission of the C-C bond of the diazadiene (dad) moiety of the trop2
      dad ligand, resulting in net (formal) nitrene, carbene, or P=C insertion in the
      dad C-C bond, respectively. Supporting DFT studies revealed that several of the
      ligand-based reactions proceed via low-barrier radical-type pathways, involving
      the dad.- ligand radical character of the OSS or triplet species.

PMID- 29341298
TI  - Multiple signaling systems target a core set of transition metal homeostasis
      genes using similar binding motifs.
AB  - Bacterial response to metals can require complex regulation. We report an
      overlapping regulation for copper and zinc resistance genes in the denitrifying
      bacterium, Pseudomonas stutzeri RCH2, by three two-component regulatory proteins
      CopR1, CopR2 and CzcR. We conducted genome-wide evaluations to identify gene
      targets of two paralogous regulators, CopR1 and CopR2, annotated for copper
      signaling, and compared the results with the gene targets for CzcR, implicated in
      zinc signaling. We discovered that the CopRs and CzcR have largely common
      targets, and crossregulate a core set of P. stutzeri copper and zinc responsive
      genes. We established that this crossregulation is enabled by a conserved binding
      motif in the upstream regulatory regions of the target genes. The crossregulation
      is physiologically relevant as these regulators synergistically and
      antagonistically target multicopper oxidases, metal efflux and sequestration
      systems. CopR1 and CopR2 upregulate two cop operons encoding copper tolerance
      genes, while all three regulators downregulate a putative copper chaperone,
      Psest_1595. CzcR also upregulated the oprD gene and the CzcIABC Zn2+ efflux
      system, while CopR1 and CopR2 downregulated these genes. Our study suggests that
      crossregulation of copper and zinc homeostasis can be advantageous, and in P.
      stutzeri this is enabled by shared binding motifs for multiple response
      regulators.

PMID- 29341299
TI  - Autonomous Purkinje cell axonal dystrophy causes ataxia in peroxisomal
      multifunctional protein-2 deficiency.
AB  - Peroxisomes play a crucial role in normal neurodevelopment and in the maintenance
      of the adult brain. This depends largely on intact peroxisomal beta-oxidation
      given the similarities in pathologies between peroxisome biogenesis disorders and
      deficiency of multifunctional protein-2 (MFP2), the central enzyme of this
      pathway. Recently, adult patients diagnosed with cerebellar ataxia were shown to
      have mild mutations in the MFP2 gene, hydroxy-steroid dehydrogenase (17 beta)
      type 4 (HSD17B4). Cerebellar atrophy also develops in MFP2 deficient mice but the
      cellular origin of the degeneration is unexplored. In order to investigate
      whether peroxisomal beta-oxidation is essential within Purkinje cells, the sole
      output neurons of the cerebellum, we generated and characterized a mouse model
      with Purkinje cell selective deletion of the MFP2 gene. We show that selective
      loss of MFP2 from mature cerebellar Purkinje neurons causes a late-onset motor
      phenotype and progressive Purkinje cell degeneration, thereby mimicking ataxia
      and cerebellar deterioration in patients with mild HSD17B4 mutations. We
      demonstrate that swellings on Purkinje cell axons coincide with ataxic behavior
      and precede neurodegeneration. Loss of Purkinje cells occurs in a characteristic
      banded pattern, proceeds in an anterior to posterior fashion and is accompanied
      by progressive astro- and microgliosis. These data prove that the peroxisomal
      beta-oxidation pathway is required within Purkinje neurons to maintain their
      axonal integrity, independent of glial dysfunction.

PMID- 29341301
TI  - Editorial.

PMID- 29341300
TI  - Inflammatory and related biomarkers are associated with post-transplant diabetes
      mellitus in kidney recipients: a retrospective study.
AB  - In this study, we investigate the association between selected inflammatory
      related biomarkers and post-transplant hyperglycemia in kidney transplant
      recipients. This retrospective analysis comprises 852 patients receiving a kidney
      transplant at the Norwegian national transplant center between 2007 and 2012, all
      having a normal oral glucose tolerance test (OGTT) before transplantation. A
      diagnostic OGTT was performed 10 weeks post-transplant to examine the association
      between inflammation-related biomarkers and two-hour plasma glucose (2HPG) by
      multivariable linear regression models adjusting for BMI, age, graft function,
      fasting insulin levels, dosage of prednisolone, and concentration of calcineurin
      inhibitors. Six of 20 biomarkers were significantly associated with 2HPG in
      multivariate analyses showing strong associations with soluble tumor necrosis
      factor type 1 (P = 0.027), Pentraxin 3 (P = 0.019), macrophage migration
      inhibitory factor (P = 0.024), and endothelial protein C receptor (P = 0.001).
      These associated markers reflect several distinct but also overlapping pathways
      including activation of tumor necrosis factor, macrophages, and endothelial
      cells. The multinomial logistic regression model showed a clear association
      between the inflammatory biomarkers and post-transplant diabetes mellitus (PTDM).
      The association between a range of inflammation markers and PTDM suggests that
      these markers may be target for future studies on pathogenesis and perhaps also
      treatment of PTDM.

PMID- 29341302
TI  - Twisted Charge-Transfer Antennae for Ultra-Bright Terbium(III) and
      Dysprosium(III) Bioprobes.
AB  - The design of original twisted charge transfer antennae in which a non-planar
      geometry is enforced thanks to one or two bulky ortho-Me substituents allows us
      to prepare the corresponding ultra-bright TbIII and DyIII bioprobes. The
      brightness of the TbIII derivative compares well with that of the benchmark Tb
      Lumi4 complex. The first bio-imaging experiments with a DyIII luminescent
      bioprobe are also reported.

PMID- 29341303
TI  - Cardiorespiratory fitness is associated with enhanced hippocampal functional
      connectivity in healthy young adults.
AB  - Consistent associations have been found between higher cardiorespiratory fitness
      (CRF) and indices of enhanced brain health and function, including behavioral
      measures of cognition as well as neuroimaging indicators such as regional brain
      volume. Several studies have reported that higher CRF levels are associated with
      a larger hippocampus, yet associations between volume and memory or functional
      connectivity metrics remain poorly understood. Using a multi-modal framework, we
      hierarchically examine the association between CRF and hippocampal volume and
      resting state functional connectivity (rsFC) in younger adults, as well as their
      relationship between with memory function. We conducted theoretically-driven
      analyses with seeds in the anterior and posterior hippocampus, as well as control
      seeds in the caudate nucleus. We tested whether (1) hippocampal connectivity with
      prefrontal cortical regions was associated with CRF in an adult sample much
      younger than traditionally tested, (2) associations between CRF and rsFC remain
      significant after adjusting for volume, and (3) volume and rsFC are related to
      memory. We found that higher CRF levels were associated with larger anterior
      hippocampal volume and more positive rsFC of the anterior hippocampus to several
      regions including the prefrontal cortex. rsFC also accounted for significant
      variance in CRF, above and beyond volume. CRF can thus be independently linked to
      increased anterior hippocampal volume, as well as stronger hippocampal rsFC in a
      population much younger than those typically tested, suggesitng it is critical to
      maintainig multiple aspects of brain health.

PMID- 29341304
TI  - Enantioselective Synthesis of Aminodiols by Sequential Rhodium-Catalysed
      Oxyamination/Kinetic Resolution: Expanding the Substrate Scope of Amidine-Based
      Catalysis.
AB  - Regio- and stereoselective oxyamination of dienes through a tandem rhodium
      catalysed aziridination-nucleophilic opening affords racemic oxazolidinone
      derivatives, which undergo a kinetic resolution acylation process with amidine
      based catalysts (ABCs) to achieve s values of up to 117. This protocol was
      applied to the enantioselective synthesis of sphingosine.

PMID- 29341306
TI  - No concession without demand.

PMID- 29341305
TI  - Plasmid-Templated Control of DNA-Cyclodextrin Nanoparticle Morphology through
      Molecular Vector Design for Effective Gene Delivery.
AB  - Engineering self-assembled superstructures through complexation of plasmid DNA
      (pDNA) and single-isomer nanometric size macromolecules (molecular nanoparticles)
      is a promising strategy for gene delivery. Notably, the functionality and overall
      architecture of the vector can be precisely molded at the atomic level by
      chemical tailoring, thereby enabling unprecedented opportunities for
      structure/self-assembling/pDNA delivery relationship studies. Beyond this notion,
      by judiciously preorganizing the functional elements in cyclodextrin (CD)-based
      molecular nanoparticles through covalent dimerization, here we demonstrate that
      the morphology of the resulting nanocomplexes (CDplexes) can be tuned, from
      spherical to ellipsoidal, rod-type, or worm-like nanoparticles, which makes it
      possible to gain understanding of their shape-dependent transfection properties.
      The experimental findings are in agreement with a shift from chelate to cross
      linking interactions on going from primary-face- to secondary-face-linked CD
      dimers, the pDNA partner acting as an active payload and as a template. Most
      interestingly, the transfection efficiency in different cells was shown to be
      differently impacted by modifications of the CDplex morphology, which has led to
      the identification of an optimal prototype for tissue-selective DNA delivery to
      the spleen in vivo.

PMID- 29341307
TI  - Chemical and Enzymatic Strategies for Bacterial and Mammalian Cell Surface
      Engineering.
AB  - The cell surface serves important functions such as the regulation of cell-cell
      and cell-environment interactions. The understanding and manipulation of the cell
      surface is important for a wide range of fundamental studies of cellular behavior
      and for biotechnological and medical applications. With the rapid advance of
      biology, chemistry and materials science, many strategies have been developed for
      the functionalization of bacterial and mammalian cell surfaces. Here, we review
      the recent development of chemical and enzymatic approaches to cell surface
      engineering with particular emphasis on discussing the advantages and limitations
      of each of these strategies.

PMID- 29341308
TI  - Stiffness regulates the proliferation and osteogenic/odontogenic differentiation
      of human dental pulp stem cells via the WNT signalling pathway.
AB  - OBJECTIVES: Researches showed that stiffness of the extracellular matrix can
      affect the differentiation of many stem cells. Dental pulp stem cells (DPSCs) are
      a promising type of adult stem cell. However, we know little about whether and
      how the behaviour of DPSCs is influenced by stiffness. MATERIALS AND METHODS: We
      carried out a study that cultured DPSCs on tunable elasticity
      polydimethylsiloxane substrates to investigate the influence on morphology,
      proliferation, osteogenic/odontogenic differentiation and its possible mechanism.
      RESULTS: Soft substrates changed the cell morphology and inhibited the
      proliferation of DPSCs. Expression of markers related to osteogenic/odontogenic
      differentiation was significantly increased as the substrate stiffness increased,
      including ALP (alkaline phosphatase), OCN (osteocalcin), OPN (osteopontin), RUNX
      2 (runt-related transcription factor-2), BMP-2 (bone morphogenetic protein-2),
      DSPP (dentin sialophosphoprotein) and DMP-1 (dentin matrix protein-1). Mechanical
      properties promote the function of DPSCs related to the Wnt signalling pathway.
      CONCLUSIONS: Our results showed that mechanical factors can regulate the
      proliferation and differentiation of DPSCs via the WNT signalling pathway. This
      provides theoretical basis to optimize dental or bone tissue regeneration through
      increasing stiffness of extracelluar matrix.

PMID- 29341309
TI  - Issue Information-Declaration of Helsinki.

PMID- 29341310
TI  - Critical appraisal of the oxidative stress pathway in vitiligo: a systematic
      review and meta-analysis.
AB  - BACKGROUND: The pathogenesis of vitiligo remains a topic of extensive debate.
      This is partly due to the moderate efficacy of current treatments. The role of
      the oxidative stress pathway in vitiligo is a popular although controversial
      research topic. OBJECTIVE: To clarify the role of the oxidative stress pathway in
      vitiligo compared to other inflammatory skin disorders and to assess the
      therapeutic role of antioxidants. METHODS: We conducted a systematic search of
      the existing literature on the aberrancies of the oxidative stress pathway in
      vitiligo. Subsequently, the efficacy of both topical and oral antioxidants in
      clinical trials was investigated. RESULTS: A deregulated oxidative pathway is
      clearly evident with elevated superoxide dismutase, decreased catalase and
      increased lipid peroxidation. However, similar results have been obtained in
      other inflammatory skin diseases such as psoriasis, atopic dermatitis, lichen
      planus and urticaria. This questions the unique role of oxidative stress in the
      development of vitiligo. Some isolated successes have been reported with oral
      ginkgo biloba, polypodium leucotomos and vitamin C and E preparations, while
      other clinical trials have failed to show reproducible results. The use of
      topical antioxidants delivers in general no beneficial results. CONCLUSION: The
      oxidative pathway is affected in vitiligo, but its unique initiating or
      contributory role in the pathogenesis is less evident. Interesting data support
      the added value of oral antioxidants in vitiligo although confirmatory studies
      are missing.

PMID- 29341311
TI  - Decreased thermal sweating of central sudomotor mechanism in African and Korean
      men.
AB  - OBJECTIVE: Tropical natives sweat less and preserve more body fluid than
      temperate natives, tolerating heat stress. However, the mechanisms involved in
      such sweating reduction have not been fully elucidated. We examined the sudomotor
      responses of men of African (n = 36) and Korean (n = 41) ancestry during hot
      water (43  degrees C) leg immersion (central sudomotor response). Correlations
      between mean body temperature, basal metabolic rate (BMR), and sweat rate were
      also examined. METHODS: All procedures were done in an automated climate chamber.
      Local skin temperatures and BMR were measured and mean body temperature was
      calculated. Sweating activities which include evaporative loss rate, sweat onset
      time, sweat rate, sweat volume, and whole-body sweat loss volume were examined.
      RESULTS: In the heat load test, Africans showed lower mean body and local skin
      temperatures than Koreans before and after heating. Before and after heating, BMR
      declined significantly in Africans, while that of Koreans declined less. Local
      sweat onset time increased more in Africans than in Koreans. Local evaporative
      loss rate, local sweat volume, local sweat rate, and whole body sweat loss volume
      were reduced in Africans compared with Koreans. There were positive associations
      of mean body temperature and resting BMR with mean sweat rate. CONCLUSION: In
      conclusion, we observed a larger reduction of sudomotor activity in tropical
      Africans than in temperate Koreans, which was associated with their lower mean
      body temperature and lower resting BMR.

PMID- 29341312
TI  - Recurrent terbinafine resistant Trichophyton rubrum infection in a child with
      congenital ichthyosis.
AB  - Dermatophytosis in children caused by Trichophyton rubrum is preferably treated
      with topical or systemic terbinafine. We report the first case of terbinafine
      resistance in a child with recurrent T. rubrum dermatophytosis and congenital
      ichthyosiform erythroderma.

PMID- 29341313
TI  - Synthesis of alpha-l-Fucopyranoside-Presenting Glycoclusters and Investigation of
      Their Interaction with Photorhabdus asymbiotica Lectin (PHL).
AB  - Photorhabdus asymbiotica is a gram-negative bacterium that is not only as
      effective an insect pathogen as other members of the genus, but it also causes
      serious diseases in humans. The recently identified lectin PHL from P.
      asymbiotica verifiably modulates an immune response of humans and insects, which
      supports the idea that the lectin might play an important role in the host
      pathogen interaction. Dimeric PHL contains up to seven l-fucose-specific binding
      sites per monomer, and in order to target multiple binding sites of PHL, alpha-l
      fucoside-containing di-, tri- and tetravalent glycoclusters were synthesized.
      Methyl gallate and pentaerythritol were chosen as multivalent scaffolds, and the
      fucoclusters were built from the above-mentioned cores by coupling with different
      oligoethylene bridges and propargyl alpha-l-fucosides using 1,3-dipolar azide
      alkyne cycloaddition. The interaction between fucoside derivates and PHL was
      investigated by several biophysical and biological methods, ITC and SPR
      measurements, hemagglutination inhibition assay, and an investigation of
      bacterial aggregation properties were carried out. Moreover, details of the
      interaction between PHL and propargyl alpha-l-fucoside as a monomer unit were
      revealed using X-ray crystallography. Besides this, the interaction with
      multivalent compounds was studied by NMR techniques. The newly synthesized
      multivalent fucoclusters proved to be up to several orders of magnitude better
      ligands than the natural ligand, l-fucose.

PMID- 29341314
TI  - Chronic sleep reduction in adolescents-clinical cut-off scores for the Chronic
      Sleep Reduction Questionnaire (CSRQ).
AB  - The Chronic Sleep Reduction Questionnaire is a validated questionnaire that
      measures symptoms of prolonged insufficient and/or poor sleep and therefore
      accounts for individuals' sleep need and sleep debt. This study extends its
      psychometric properties by providing cut-off scores, using a matched sample of
      298 healthy adolescents (15.38 +/- 1.63 years, 37.9% male, mean Chronic Sleep
      Reduction Questionnaire score: 32.98 +/- 6.51) and 298 adolescents with
      insomnia/delayed sleep-wake phase disorder (15.48 +/- 1.62 years; 37.9% male,
      mean Chronic Sleep Reduction Questionnaire score: 42.59 +/- 7.06). We found an
      area under the curve of 0.84 (95% confidence interval: 0.81-0.87). Cut-off scores
      for optimal sensitivity, optimal specificity and based on Youden's criterion are
      provided. These cut-off scores are highly relevant for use of the Chronic Sleep
      Reduction Questionnaire in future studies and clinical practice.

PMID- 29341315
TI  - Use of quantitative real-time PCR to determine viability of Streptococcus equi
      subspecies equi in respiratory secretions from horses with strangles.
AB  - BACKGROUND: In recent years, molecular approaches have been able to characterise
      the viability of equine upper respiratory tract pathogens using absolute
      molecular quantitation as well as detection of transcripts for virulence genes.
      OBJECTIVES: The objective of this study was to investigate molecular surrogates
      for S. equi subspecies equi (S. equi) viability in biological samples from horses
      with strangles. STUDY DESIGN: Retrospective cross-sectional study. METHODS: S.
      equi culture-positive and culture-negative upper airway secretions were assessed
      by qPCR at the genomic (gDNA) and complimentary DNA (cDNA) level for various
      target genes (SeM, SEQ2190, eqbE and szpSe). Absolute quantitation was performed
      using standard curves, and the results were expressed as number of S. equi target
      genes per MUl of gDNA or cDNA. Additionally, the presence or absence of S. equi
      gene expression for the various target genes was assessed and compared with the
      culture results. RESULTS: While all 21 culture-positive samples tested S.
      equiqPCR positive, up to 43.7 and 18.9% of 64 culture-negative samples tested
      qPCR positive at the gDNA and cDNA level, respectively. Significant differences
      in absolute quantitation for S. equi at the gDNA level were found between culture
      positive and culture-negative samples. When absolute quantitation of S. equi
      target genes at the gDNA level was assessed with the presence or absence of
      transcripts, there was a significantly higher S. equi target gene number in
      samples with expression of transcripts compared with samples with no expression
      of transcripts. MAIN LIMITATIONS: The lack of standardisation of samples
      collected in the field and the delay from sample collection to samples processing
      may have negatively affected the cultivability of S. equi and mRNA quality.
      CONCLUSIONS: Molecular viability for S. equi can be investigated by determining
      absolute quantitation and/or by detecting mRNA for specific target genes.
      However, veterinarians have to be cautioned that any qPCR-positive result for S.
      equi needs to be taken seriously and trigger biosecurity protocols aimed at
      reducing spread.

PMID- 29341316
TI  - Deferoxamine promotes mesenchymal stem cell homing in noise-induced injured
      cochlea through PI3K/AKT pathway.
AB  - OBJECTIVE: Over 5% of the world's population suffers from disabling hearing loss.
      Stem cell homing in target tissue is an important aspect of cell-based therapy,
      which its augmentation increases cell therapy efficiency. Deferoxamine (DFO) can
      induce the Akt activation, and phosphorylation status of AKT (p-AKT) upregulates
      CXC chemokine receptor-4 (CXCR4) expression. We examined whether DFO can enhance
      mesenchymal stem cells (MSCs) homing in noise-induced damaged cochlea by PI3K/AKT
      dependent mechanism. MATERIALS AND METHODS: Mesenchymal stem cells were treated
      with DFO. AKT, p-AKT protein and hypoxia inducible factor 1- alpha (HIF-1alpha)
      and CXCR4 gene and protein expression was evaluated by RT- PCR and Western blot
      analysis. For in vivo assay, rats were assigned to control, sham, noise exposure
      groups without any treatment or receiving normal, DFO-treated and DFO +LY294002
      (The PI3K inhibitor)-treated MSCs. Following chronic exposure to 115 dB white
      noise, MSCs were injected into the rat cochlea through the round window. Number
      of Hoechst- labelled cells was determined in the endolymph after 24 hours.
      RESULTS: Deferoxamine increased P-AKT, HIF-1alpha and CXCR4 expression in MSCs
      compared to non-treated cells. DFO pre-conditioning significantly increased the
      homing ability of MSCs into injured ear compared to normal MSCs. These effects of
      DFO were blocked by LY294002. CONCLUSIONS: Pre-conditioning of MSCs by DFO before
      transplantation can improve stem cell homing in the damaged cochlea through
      PI3K/AKT pathway activation.

PMID- 29341317
TI  - Apoptosis induction in K562 human myelogenous leukaemia cells is connected to the
      modulation of Wnt/beta-catenin signalling by BHX, a novel pyrazoline derivative.
AB  - OBJECTIVES: The goal of this study was to explore the effects of BHX on human
      chronic myeloid leukaemia (CML) cells and to elucidate the underlying molecular
      mechanism. MATERIALS AND METHODS: CML cell line K562 cells were treated with BHX.
      The effects of BHX on cell proliferation, apoptosis and cell cycle were detected.
      Subsequently, the caspase, ATP activity, Ca2+ , ROS and mitochondrial membrane
      potential (MMP) levels treated with various concentrations of BHX were analysed.
      The variation of relevant proteins and genes was detected. Further, toxicity of
      BHX on peripheral blood cells, bone marrow-nucleated cells (BMNC) and organ index
      were investigated on mice. RESULTS: Results showed that BHX suppressed K562 cell
      proliferation in a dose-dependent manner and induced apoptosis and G0/G1 phase
      arrest. BHX induced mitochondria-mediated apoptosis, which was associated with
      downregulation of MMP, activation of caspase-3 and caspase-9, generation of
      intracellular ROS and elevation of Ca2+ in K562 cells. In treated cells, ATP
      levels were decreased, expression of total beta-catenin, phosphorylated beta
      catenin and beta-catenin in the nucleus was decreased, and expression of cell
      cycle-related proteins was decreased. Further analysis revealed that BHX lowered
      the transcriptional level of beta-catenin. Lastly, BHX treatment significantly
      reduced the number of white blood cells, but had no effect on BMNC and organ
      index. CONCLUSIONS: These findings provide further insight into the potential use
      of BHX as an anti-cancer agent against human leukaemia.

PMID- 29341318
TI  - Cognitive trajectories and spectrum of neuropathology in SuperAgers: The first 10
      cases.
AB  - On average, memory capacity is significantly higher in populations of 50-60 year
      olds than in populations of 80 year olds. We define SuperAgers as individuals 80
      or older whose episodic memory capacity is at least as good as that of
      cognitively average individuals in their 50s and 60s. SuperAgers therefore have
      memory capacity that is superior for age. Previous work showed that SuperAgers
      have greater cortical volumes and greater resistance to age-related cortical
      atrophy than "cognitively average" individuals of the same age. Here we report on
      the cognitive, personality, and neuropathologic characteristics of the first 10
      autopsy cases in the Northwestern SuperAging Program. During the follow-up
      period, seven SuperAgers maintained episodic memory performance within or above
      the average range for 50-65 year-old norms and all 10 SuperAgers maintained
      episodic memory scores within normal limits for their own age. Openness to
      experience scores tended to be high on the NEO-PI-R measure of personality. The
      10 autopsy specimens showed variable findings within the spectrum of Alzheimer
      pathology. The hippocampus and entorhinal cortex contained neurofibrillary
      degeneration mostly in the Braak II-III stages. However, even these limbic areas
      contained many healthy appearing neurons and the neocortex was generally free of
      neurofibrillary degeneration. In contrast, neocortical areas in at least five of
      the cases contained moderate to high densities of neuritic plaques. These
      findings need to be placed in context by comparing them to the neuropathology of
      cognitively average individuals of the same age. Future research on SuperAgers is
      likely to offer insights into factors that either prevent the emergence of
      involutional changes in the brain or that makes cognitive function more resistant
      to their consequences.

PMID- 29341319
TI  - Crosslinking of Semiaromatic Polyesters toward High-Temperature Shape Memory
      Polymers with Full Recovery.
AB  - In this work, high-temperature shape memory polymers are realized by end-group
      crosslinking of the semiaromatic polyesters polyethylene terephthalate as well as
      polybutylene terephthalate. Both networks exhibit trigger temperatures distinctly
      higher than 200  degrees C and excellent shape memory properties such as storable
      strains of 200%, full fixity of the applied strain in the temporary shape, and
      full recovery of the permanent shape.

PMID- 29341320
TI  - Spatiotemporal, metabolic, and therapeutic characterization of altered functional
      connectivity in major depressive disorder.
AB  - Although imbalanced functional integration has been increasingly reported in
      major depressive disorder (MDD), there still lacks a general framework to
      characterize common characteristic and origin shared by the integrative
      disturbances. Here we examined spatial selectivity, temporal uniqueness,
      metabolic basis, and therapeutic response of altered functional connectivity (FC)
      in MDD by analyzing both cross-sectional and longitudinal multimodal functional
      magnetic resonance imaging data from 35 patients and 34 demographically matched
      healthy controls. First, based on a voxel-wise, data-driven, graph-based degree
      centrality approach, the bilateral anterior cingulate gyri, middle frontal gyri
      and superior frontal gyri, and the right parahippocampal gyrus were robustly
      identified to show decreased FC in MDD. Further spatiotemporal analyses revealed
      that these regions exhibited hub-like features and were selectively located in
      limbic and default mode networks spatially and, relative to other areas in the
      brain, exhibited unique, frequency-dependent oscillation power (stronger within
      0.01-0.027 Hz and weaker within 0.027-0.073 Hz) and less dynamical variability of
      whole-brain FC profiles temporally. Moreover, a cross-modality fusion analysis
      showed that all MDD-related FC impairments were associated with reduced cerebral
      blood flow (CBF); however, there existed multiple regions that showed reduced CBF
      but had intact FC in the patients, which resulted in a decreased FC-CBF coupling
      and implied an earlier emergence of reduced CBF than impaired FC in MDD. Finally,
      the disrupted FC in MDD gradually recovered over the course of drug treatment (2
      and 12 weeks). Altogether, these findings could help establish a general
      framework to provide mechanistic insights into integrative dysfunctions in MDD.

PMID- 29341321
TI  - Interleukin-6 contributes to chemoresistance in MDA-MB-231 cells via targeting
      HIF-1alpha.
AB  - Chemoresistance is a critical challenge in the clinical treatment of triple
      negative breast cancer (TNBC). It has been well documented that inflammatory
      mediators from tumor microenvironment are involved in the pathogenesis of TNBC
      and might be related to chemoresistance of cancer cells. In this study, the
      contribution of interleukin-6 (IL-6), one of the principal oncogenic molecules,
      in chemoresistance of a TNBC cell line MDA-MB-231 was first investigated. The
      results showed that IL-6 treatment could induce upregulation of HIF-1alpha via
      the activation of STAT3 in MDA-MB-231 cells, which consequently contributed to
      its effect against chemotherapeutic drug-induced cytotoxicity and cell apoptosis.
      However, knockdown of HIF-1alpha attenuated such effect via affecting the
      expressions of apoptosis-related molecules as Bax and Bcl-2 and drug transporters
      as P-gp and MRP1. This study indicated that targeting at IL-6/HIF-1alpha
      signaling pathway might be an effective strategy to overcome chemoresistance in
      TNBC therapy.

PMID- 29341322
TI  - Isthmus sites identified by Ripple Mapping are usually anatomically stable: A
      novel method to guide atrial substrate ablation?
AB  - BACKGROUND: Postablation reentrant ATs depend upon conducting isthmuses bordered
      by scar. Bipolar voltage maps highlight scar as sites of low voltage, but the
      voltage amplitude of an electrogram depends upon the myocardial activation
      sequence. Furthermore, a voltage threshold that defines atrial scar is unknown.
      We used Ripple Mapping (RM) to test whether these isthmuses were anatomically
      fixed between different activation vectors and atrial rates. METHODS: We studied
      post-AF ablation ATs where >1 rhythm was mapped. Multipolar catheters were used
      with CARTO Confidense for high-density mapping. RM visualized the pattern of
      activation, and the voltage threshold below which no activation was seen.
      Isthmuses were characterized at this threshold between maps for each patient.
      RESULTS: Ten patients were studied (Map 1 was AT1; Map 2: sinus 1/10, LA paced
      2/10, AT2 with reverse CS activation 3/10; AT2 CL difference 50 +/- 30 ms). Point
      density was similar between maps (Map 1: 2,589 +/- 1,330; Map 2: 2,214 +/- 1,384;
      P  =  0.31). RM activation threshold was 0.16 +/- 0.08 mV. Thirty-one isthmuses
      were identified in Map 1 (median 3 per map; width 27 +/- 15 mm; 7 anterior; 6
      roof; 8 mitral; 9 septal; 1 posterior). Importantly, 7 of 31 (23%) isthmuses were
      unexpectedly identified within regions without prior ablation. AT1 was treated
      following ablation of 11/31 (35%) isthmuses. Of the remaining 20 isthmuses, 14 of
      16 isthmuses (88%) were consistent between the two maps (four were inadequately
      mapped). Wavefront collision caused variation in low voltage distribution in 2 of
      16 (12%). CONCLUSIONS: The distribution of isthmuses and nonconducting tissue
      within the ablated left atrium, as defined by RM, appear concordant between
      rhythms. This could guide a substrate ablative approach.

PMID- 29341323
TI  - Test-retest reliability and longitudinal analysis of automated hippocampal
      subregion volumes in healthy ageing and Alzheimer's disease populations.
AB  - The hippocampal formation is a complex brain structure that is important in
      cognitive processes such as memory, mood, reward processing and other executive
      functions. Histological and neuroimaging studies have implicated the hippocampal
      region in neuropsychiatric disorders as well as in neurodegenerative diseases.
      This highly plastic limbic region is made up of several subregions that are
      believed to have different functional roles. Therefore, there is a growing
      interest in imaging the subregions of the hippocampal formation rather than
      modelling the hippocampus as a homogenous structure, driving the development of
      new automated analysis tools. Consequently, there is a pressing need to
      understand the stability of the measures derived from these new techniques. In
      this study, an automated hippocampal subregion segmentation pipeline, released as
      a developmental version of Freesurfer (v6.0), was applied to T1-weighted magnetic
      resonance imaging (MRI) scans of 22 healthy older participants, scanned on 3
      separate occasions and a separate longitudinal dataset of 40 Alzheimer's disease
      (AD) patients. Test-retest reliability of hippocampal subregion volumes was
      assessed using the intra-class correlation coefficient (ICC), percentage volume
      difference and percentage volume overlap (Dice). Sensitivity of the regional
      estimates to longitudinal change was estimated using linear mixed effects (LME)
      modelling. The results show that out of the 24 hippocampal subregions, 20 had ICC
      scores of 0.9 or higher in both samples; these regions include the molecular
      layer, granule cell layer of the dentate gyrus, CA1, CA3 and the subiculum (ICC >
      0.9), whilst the hippocampal fissure and fimbria had lower ICC scores (0.73
      0.88). Furthermore, LME analysis of the independent AD dataset demonstrated
      sensitivity to group and individual differences in the rate of volume change over
      time in several hippocampal subregions (CA1, molecular layer, CA3, hippocampal
      tail, fissure and presubiculum). These results indicate that this automated
      segmentation method provides a robust method with which to measure hippocampal
      subregions, and may be useful in tracking disease progression and measuring the
      effects of pharmacological intervention.

PMID- 29341324
TI  - Beta testing the potential link between the alpha antagonist tamsulosin and
      dementia.

PMID- 29341325
TI  - Characterization of Adrenal Lesions on Unenhanced MRI Using Texture Analysis: A
      Machine-Learning Approach.
AB  - BACKGROUND: Adrenal adenomas (AA) are the most common benign adrenal lesions,
      often characterized based on intralesional fat content as either lipid-rich (LRA)
      or lipid-poor (LPA). The differentiation of AA, particularly LPA, from nonadenoma
      adrenal lesions (NAL) may be challenging. Texture analysis (TA) can extract
      quantitative parameters from MR images. Machine learning is a technique for
      recognizing patterns that can be applied to medical images by identifying the
      best combination of TA features to create a predictive model for the diagnosis of
      interest. PURPOSE/HYPOTHESIS: To assess the diagnostic efficacy of TA-derived
      parameters extracted from MR images in characterizing LRA, LPA, and NAL using a
      machine-learning approach. STUDY TYPE: Retrospective, observational study.
      POPULATION/SUBJECTS/PHANTOM/SPECIMEN/ANIMAL MODEL: Sixty MR examinations,
      including 20 LRA, 20 LPA, and 20 NAL. FIELD STRENGTH/SEQUENCE: Unenhanced T1 
      weighted in-phase (IP) and out-of-phase (OP) as well as T2 -weighted (T2 -w) MR
      images acquired at 3T. ASSESSMENT: Adrenal lesions were manually segmented,
      placing a spherical volume of interest on IP, OP, and T2 -w images. Different
      selection methods were trained and tested using the J48 machine-learning
      classifiers. STATISTICAL TESTS: The feature selection method that obtained the
      highest diagnostic performance using the J48 classifier was identified; the
      diagnostic performance was also compared with that of a senior radiologist by
      means of McNemar's test. RESULTS: A total of 138 TA-derived features were
      extracted; among these, four features were selected, extracted from the IP
      (Short_Run_High_Gray_Level_Emphasis), OP (Mean_Intensity and
      Maximum_3D_Diameter), and T2 -w (Standard_Deviation) images; the J48 classifier
      obtained a diagnostic accuracy of 80%. The expert radiologist obtained a
      diagnostic accuracy of 73%. McNemar's test did not show significant differences
      in terms of diagnostic performance between the J48 classifier and the expert
      radiologist. DATA CONCLUSION: Machine learning conducted on MR TA-derived
      features is a potential tool to characterize adrenal lesions. LEVEL OF EVIDENCE:
      4 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018.

PMID- 29341326
TI  - Elevated leukocyte count in cerebrospinal fluid of patients with chronic
      inflammatory demyelinating polyneuropathy.
AB  - Cerebrospinal fluid (CSF) examination is often part of the diagnostic work-up of
      a patient suspected of having chronic inflammatory demyelinating polyneuropathy
      (CIDP). According to the European Federation of Neurological Societies and the
      Peripheral Nerve Society (EFNS/PNS) criteria, an elevated protein level without
      pleocytosis (leukocytes <10 cells/ul) is supportive of the diagnosis CIDP. It is
      unclear how many CSF leukocytes are compatible with the diagnosis CIDP and how
      extensive the diagnostic work-up should be in patients with a demyelinating
      neuropathy and pleocytosis. We performed a retrospective study at two tertiary
      neuromuscular referral clinics and identified 14 out of 273 (6%) patients with
      CIDP with elevated CSF leukocytes (>=10 cells/ul). All these patients met the
      EFNS/PNS criteria for definite or probable CIDP. Eight patients (57%) presented
      with a subacute onset and four patients with an antecedent infection. Most
      patients responded well to therapy, and eight patients are currently in
      remission. In four patients, lumbar puncture was repeated. A spontaneous decrease
      in leukocytes before start of treatment was found in three patients. Our data
      indicate that a mild to moderate pleocytosis in CSF does not exclude the
      diagnosis of CIDP, especially in patients with a subacute onset of disease.

PMID- 29341329
TI  - Violence and child mental health in Brazil: The Itaborai Youth Study methods and
      findings.
AB  - OBJECTIVES: To demonstrate a study design that could be useful in low-resource
      and violent urban settings and to estimate the prevalence of child violence
      exposure (at home, community, and school) and child mental health problems in a
      low-income medium-size city. METHODS: The Itaborai Youth Study is a Norway-Brazil
      collaborative longitudinal study conducted in Itaborai city (n = 1409, 6-15 year
      olds). A 3-stage probabilistic sampling plan (random selection of census units,
      eligible households, and target child) generated sampling weights that were used
      to obtain estimates of population prevalence rates. RESULTS: Study strengths
      include previous pilot study and focus groups (testing procedures and
      comprehension of questionnaire items), longitudinal design (2 assessment periods
      with a mean interval of 12.9 months), high response rate (>80%), use of
      standardized instruments, different informants (mother and adolescent), face-to
      face interviews to avoid errors due to the high frequency of low-educated
      respondents, and information gathered on a variety of potential predictors and
      protective factors. Children and adolescents presented relevant levels of
      violence exposure and clinical mental health problems. CONCLUSIONS: Prevalence
      estimates are probably valid to other Brazilian low-income medium-size cities due
      to similarities in terms of precarious living conditions. Described study methods
      could be useful in other poor and violent world regions.

PMID- 29341328
TI  - Histiocytosis - cutaneous manifestations of hematopoietic neoplasm and non
      neoplastic histiocytic proliferations.
AB  - Histiocytoses are rare disorders characterized by the accumulation of cells
      derived from macrophages, dendritic cells or monocytes in various tissues. There
      is a broad spectrum of disease manifestations with some subtypes commonly showing
      skin lesions, while in others, the skin is rarely involved. Here, we describe
      cutaneous manifestations of histiocytoses belonging to the Langerhans group (L
      group), the group of cutaneous and mucocutaneous histiocytoses (C group) and the
      group of Rosai-Dorfman disease (RDD) and related histiocytoses (R group)
      according to the current classification. Characteristic clinical presentations
      noted were a rust-brown colour or xanthomatous aspect in many cases of
      histiocytoses. Histological criteria for differentiation are described.
      Immunohistochemistry shows positivity for S100 and CD1a in Langerhans-cell
      histiocytoses (LHCH) of the L group, while CD68 positivity with S100 and CD1a
      negativity are typical in histiocytoses of the C group of cutaneous and
      mucocutaneous histiocytoses. RDD in the R group shows positivity for S100 and
      CD68, while CD1a is negative. We further review the pathogenesis of LHCH based on
      insights on the central role of the mitogen-activated protein (MAPK) kinase
      pathway. Common mutations in various histiocytic populations of diverse ontogeny
      and at different stages of differentiation may be responsible for the diverse
      clinical picture of this neoplastic entity. For histiocytoses of the C group and
      R group, a reactive origin is discussed with the exception of the disseminated
      form of juvenile xanthogranuloma. We suggest exploring the role of an origin from
      skin residing histiocytes for the isolated cutaneous manifestation in some types.
      With regard to therapeutic options, skin-directed therapies are the first choice
      in limited disease, while systemic chemotherapy has traditionally been used in
      extensive disease. In Langerhans-cell histiocytoses and related entities, therapy
      by BRAF inhibition has led to a breakthrough especially in patients with an
      activation of the MAPK pathway.

PMID- 29341327
TI  - Involvement of the dorsal hippocampus in expression and extinction of cocaine
      induced conditioned place preference.
AB  - A key aspect of substance abuse is that drug taking often occurs in a specific
      context. As a consequence, exposure to drug-associated contexts can trigger
      cravings and relapse, even after long periods of abstinence. Although many
      studies have demonstrated that the hippocampus is critical for developing and
      retrieving contextual and spatial memories, comparatively little is known about
      the role of the hippocampus in acquiring and inhibiting memories involving
      contexts and drugs of abuse. We examined the effects of hippocampal inactivation
      on expression of cocaine-induced conditioned place preference (CPP) after initial
      acquisition or extinction of CPP in C57BL/6 mice. During acquisition of CPP,
      distinct tactile cues were paired with cocaine (20 mg kg-1 , intraperitoneal,
      CS+) and different tactile cues were paired with saline (CS-) on alternate days.
      Groups differed in whether the CS+ and CS- cues were presented in the same large
      space (one-compartment procedure) or distinct small spaces (two-compartment
      procedure), as previous findings demonstrate that a two-compartment configuration
      facilitates acquisition and attenuates extinction of a cocaine-induced CPP.
      Microinjection of the GABAA agonist, muscimol, into the dorsal hippocampus
      impaired (1) retrieval of a place preference after acquisition, (2) extinction of
      a place preference, and (3) retrieval of extinction. These effects differed
      depending on the spatial configuration during acquisition or extinction,
      suggesting that the dorsal hippocampus may differentially modulate drug seeking
      during retrieval and extinction of CPP.

PMID- 29341330
TI  - Real-Time and High-Resolution Bioimaging with Bright Aggregation-Induced Emission
      Dots in Short-Wave Infrared Region.
AB  - Fluorescence imaging in the spectral region beyond the conventional near-infrared
      biological window (700-900 nm) can theoretically afford high resolution and deep
      tissue penetration. Although some efforts have been devoted to developing a short
      wave infrared (SWIR; 900-1700 nm) imaging modality in the past decade, long
      wavelength biomedical imaging is still suboptimal owing to the unsatisfactory
      materials properties of SWIR fluorophores. Taking advantage of organic dots based
      on an aggregation-induced emission luminogen (AIEgen), herein microscopic
      vasculature imaging of brain and tumor is reported in living mice in the SWIR
      spectral region. The long-wavelength emission of AIE dots with certain brightness
      facilitates resolving brain capillaries with high spatial resolution (~3 um) and
      deep penetration (800 um). Owning to the deep penetration depth and real-time
      imaging capability, in vivo SWIR microscopic angiography exhibits superior
      resolution in monitoring blood-brain barrier damage in mouse brain, and
      visualizing enhanced permeability and retention effect in tumor sites.
      Furthermore, the AIE dots show good biocompatibility, and no noticeable
      abnormalities, inflammations or lesions are observed in the main organs of the
      mice. This work will inspire new insights on development of advanced SWIR
      techniques for biomedical imaging.

PMID- 29341331
TI  - The relationship between thalamic GABA content and resting cortical rhythm in
      neuropathic pain.
AB  - Recurrent thalamocortical connections are integral to the generation of brain
      rhythms and it is thought that the inhibitory action of the thalamic reticular
      nucleus is critical in setting these rhythms. Our work and others' has suggested
      that chronic pain that develops following nerve injury, that is, neuropathic
      pain, results from altered thalamocortical rhythm, although whether this
      dysrhythmia is associated with thalamic inhibitory function remains unknown. In
      this investigation, we used electroencephalography and magnetic resonance
      spectroscopy to investigate cortical power and thalamic GABAergic concentration
      in 20 patients with neuropathic pain and 20 pain-free controls. First, we found
      thalamocortical dysrhythmia in chronic orofacial neuropathic pain; patients
      displayed greater power than controls over the 4-25 Hz frequency range, most
      marked in the theta and low alpha bands. Furthermore, sensorimotor cortex
      displayed a strong positive correlation between cortical power and pain
      intensity. Interestingly, we found no difference in thalamic GABA concentration
      between pain subjects and control subjects. However, we demonstrated significant
      linear relationships between thalamic GABA concentration and enhanced cortical
      power in pain subjects but not controls. Whilst the difference in relationship
      between thalamic GABA concentration and resting brain rhythm between chronic pain
      and control subjects does not prove a cause and effect link, it is consistent
      with a role for thalamic inhibitory neurotransmitter release, possibly from the
      thalamic reticular nucleus, in altered brain rhythms in individuals with chronic
      neuropathic pain.

PMID- 29341333
TI  - Bronsted Base-Catalyzed Umpolung Intramolecular Cyclization of Alkynyl Imines.
AB  - A novel "umpolung" intramolecular cyclization of alkynyl imines, in which the
      electrophilic imine sp2 -carbon formally serves as a nucleophilic site, was
      developed under Bronsted base catalysis. The reaction involves the unprecedented
      catalytic generation of alpha-aminoester enolates from alpha-iminoesters via the
      1,2-addition of the anion of a secondary phosphite to an imine moiety followed by
      the [1,2]-rearrangement of a dialkoxyphosphoryl moiety from carbon to nitrogen,
      which is a formal umpolung process, and the intramolecular addition to an alkyne.
      This is a rare example of a [1,2]-rearrangement of a dialkoxyphosphoryl moiety
      from carbon to nitrogen to generate an alpha-amino carbanion and the first
      catalytic carbon-carbon bond forming reaction utilizing the resulting carbanion
      as a nucleophile.

PMID- 29341332
TI  - Cornea-Derived Mesenchymal Stromal Cells Therapeutically Modulate Macrophage
      Immunophenotype and Angiogenic Function.
AB  - Macrophages are crucial drivers of inflammatory corneal neovascularization and
      thus are potential targets for immunomodulatory therapies. We hypothesized that
      therapeutic use of cornea-derived mesenchymal stromal cells (cMSCs) may alter the
      function of macrophages. We found that cMSCs can modulate the phenotype and
      angiogenic function of macrophages. In vitro, cMSCs induce apoptosis of
      macrophages while preferentially promoting a distinct CD14hi CD16hi CD163hi
      CD206hi immunophenotype that has significantly reduced angiogenic effects based
      on in vitro angiogenesis assays. In vivo, application of cMSCs to murine corneas
      after injury leads to reduced macrophage infiltration and higher expression of
      CD206 in macrophages. Macrophages cocultured ("educated") by cMSCs express
      significantly higher levels of anti-angiogenic and anti-inflammatory factors
      compared with control macrophages. In vivo, injured corneas treated with cMSC
      educated macrophages demonstrate significantly less neovascularization compared
      with corneas treated with control macrophages. Knocking down the expression of
      pigment epithelial derived factor (PEDF) in cMSCs significantly abrogates its
      modulating effects on macrophages, as shown by the reduced rate of apoptosis,
      decreased expression of sFLT-1/PEDF, and increased expression of vascular
      endothelial growth factor-A in the cocultured macrophages. Similarly, cMSCs
      isolated from PEDF knockout mice are less effective compared with wild-type cMSCs
      at inhibiting macrophage infiltration when applied to wild-type corneas after
      injury. Overall, these results demonstrate that cMSCs therapeutically suppress
      the angiogenic capacity of macrophages and highlight the role of cMSC secreted
      PEDF in the modulation of macrophage phenotype and function. Stem Cells
      2018;36:775-784.

PMID- 29341334
TI  - Incidence and prognostic impact of cytogenetic aberrations in patients with
      systemic mastocytosis.
AB  - The clinical behavior of systemic mastocytosis (SM) is strongly associated with
      activating mutations in KIT (D816V in >80% of cases), with the severity of the
      phenotype influenced by additional somatic mutations, for example, in SRSF2,
      ASXL1, or RUNX1. Complex molecular profiles are frequently associated with the
      presence of an associated hematologic neoplasm (AHN) and an unfavorable clinical
      outcome. However, little is known about the incidence and prognostic impact of
      cytogenetic aberrations. We analyzed cytogenetic and molecular characteristics of
      109 patients (KIT D816V+, n = 102, 94%) with indolent (ISM, n = 26) and advanced
      SM (n = 83) with (n = 73, 88%) or without AHN. An aberrant karyotype was
      identified in SM-AHN (16/73, 22%) patients only. In patients with an aberrant
      karyotype, additional somatic mutations were identified in 12/16 (75%) patients.
      Seven of 10 (70%) patients with a poor-risk karyotype, for example, monosomy 7 or
      complex karyotype, and 1/6 (17%) patients with a good-risk karyotype progressed
      to secondary acute myeloid leukemia (n = 7) or mast cell leukemia (n = 1) within
      a median of 40 months (range 2-190, P = .04). In advanced SM, the median overall
      survival (OS) of poor-risk karyotype patients was significantly shorter than in
      good-risk/normal karyotype patients (4 vs 39 months; hazard ratio 11.7, 95% CI
      5.0-27.3; P < .0001). Additionally, the shortened OS in patients with poor-risk
      karyotype was independent from the mutation status. In summary, a poor-risk
      karyotype is an independent prognostic variable in advanced SM. Cytogenetic and
      molecular analyses should be routinely performed in all patients with advanced SM
      +/- AHN because these investigations greatly support prognostication and
      treatment decisions.

PMID- 29341335
TI  - Osteogenic efficacy of BMP-2 mixed with hydrogel and bone substitute in peri
      implant dehiscence defects in dogs: 16 weeks of healing.
AB  - OBJECTIVES: The objective of this study was to determine the effect of bone
      morphogenetic protein-2 (BMP-2) mixed with either polyethylene glycol hydrogel or
      synthetic bone substitute (SBS) on new bone formation in peri-implant dehiscence
      defects after 16 weeks of healing. MATERIALS AND METHODS: A guided bone
      regeneration procedure was performed in box-type peri-implant defects that were
      surgically prepared in six beagle dogs. The following four experimental groups
      were used (i) control (no graft), (ii) SBS+hydrogel, (iii) SBS+BMP-2/hydrogel and
      (iv) BMP-2/SBS+hydrogel. Volumetric analysis using micro-computed tomography and
      histomorphometric analysis was performed at 16 weeks post-operatively. RESULTS:
      The amount of new bone and the total augmented volume did not differ
      significantly between both BMP-treated groups and the SBS+hydrogel group (p >
      .05). Likewise, no histometric differences were observed in the values of new
      bone area and bone-to-implant contact ratio among the three augmentation groups
      (new bone area: 0.06 +/- 0.08, 0.19 +/- 0.20, 0.48 +/- 0.37 and 0.56 +/- 0.60 mm2
      [mean +/- standard deviation] in groups 1-4, respectively; bone-to-implant
      contact: 9.44 +/- 11.51%, 19.91 +/- 15.19%, 46.31 +/- 29.82% and 42.58 +/- 26.27%
      in groups 1-4, respectively). CONCLUSION: The osteogenic efficacy of BMP-2 on the
      regeneration of peri-implant bone defects was not detectable after 16 weeks
      regardless of the carrier materials.

PMID- 29341336
TI  - Identification of perioperative pulmonary aspiration in children using quality
      assurance and hospital administrative billing data.
AB  - BACKGROUND: Perioperative aspiration is a rare but potentially devastating
      complication, occurring in 1-10 per 10 000 anesthetics based on studies of
      quality assurance databases. Quality assurance reporting is known to
      underestimate the incidence of adverse outcomes, but few large studies use
      supplementary data sources. This study aims to identify the incidence of and risk
      factors for perioperative aspiration in children using quality assurance data
      supplemented by administrative billing records, and to examine the utility of
      billing data as a supplementary data source. METHODS: Aspiration events for
      children receiving anesthesia at a tertiary care pediatric hospital between 2008
      and 2014 were identified using (i) a perioperative quality assurance database and
      (ii) hospital administrative billing records with International Classification of
      Diseases, Ninth Revision Clinical Modification coded diagnoses of aspiration.
      Records were subject to review by pediatric anesthesiologists. Following
      identification of all aspiration events, the incidence of perioperative
      aspiration was calculated and risk factors were assessed. RESULTS: 47 272
      anesthetic cases were evaluated over 7 years. The quality assurance database
      identified 20 cases of perioperative aspiration occurring in surgical inpatients,
      same-day admissions, and outpatients. Using hospital administrative data (which
      excludes outpatients with shorter than a 24-hour stay), 9 cases of perioperative
      aspiration were identified of which 6 had not been found through quality
      assurance data. Overall, International Classification of Diseases, Ninth Revision
      coding demonstrated a positive predictive value of 94.5% for any aspiration
      event; however, positive predictive value was <4% for perioperative aspiration. A
      total incidence of 5.5 perioperative aspirations per 10 000 (95% CI: 3.7-8.0 per
      10 000) anesthetics was found. CONCLUSION: Quality assurance data offer an
      efficient way to measure the incidence of rare events, but may underestimate
      perioperative complications. International Classification of Diseases, Ninth
      Revision codes for aspiration used as a secondary data source were nonspecific
      for perioperative aspiration, but when combined with record review yielded a 30%
      increase in identified cases of aspiration over quality assurance data alone. The
      use of administrative data therefore holds potential for supplementing quality
      assurance studies of rare complications.

PMID- 29341337
TI  - Endoscopic endonasal approach for sinonasal and anterior skull base malignancies
      in the elderly.
AB  - BACKGROUND: The purpose of this study was to report the outcomes of endoscopic
      transnasal resection for sinonasal and anterior skull-base cancers in elderly
      patients. METHODS: A retrospective review was performed. The patients were
      divided into 2 groups, <70 years old and >=70 years old and compared by
      univariate analysis. Prognostic factors were evaluated with a multivariate
      analysis. Survival rates were also calculated. RESULTS: Two hundred three elderly
      patients and 397 younger patients were enrolled in this study. The elderly
      patients reported lower survival rates than the younger patients. When melanoma
      and esthesioneuroblastoma were censored, the disease-specific survival (DSS) and
      recurrence-free survival (RFS) were similar. Complication rates were 17.5%
      without any statistical significance between the groups. Multivariate analysis
      revealed that histology, stage, surgical margins, and surgical approaches were
      independent predictors of survival in elderly patients. CONCLUSION: The
      endoscopic transnasal approach reported low mortality and morbidity rates also in
      geriatric patients, and age itself is not to be considered as a contraindication.

PMID- 29341338
TI  - Human teeth biobank: Microbiological analysis of the teeth storage solution.
AB  - The cross-infections may occur during handling of dental elements, affecting the
      health of dental practitioners and researchers. This study aimed to analyze the
      influence of the storage medium temperature on the bacterial contingent of the
      human teeth used for research purposes. Thirty human teeth were donated to the
      Human Teeth Biobank immediately after extraction. The teeth were cleaned with tap
      water and neutral soap. The teeth were randomly distributed according to the
      temperature of the storage solution (deionized water): at 4  degrees C
      (refrigerator) or at -10  degrees C (freezer) and were stored individually in
      sterile vials during 60 days. After this period, a microbiological analysis
      (CFU/mL) of the storage solutions was performed and teeth were submitted to SEM
      analysis. Data were analyzed by Kruskal-Wallis test followed by Dunn's post-test
      (p <= .05). Total aerobic bacteria ranged from 5.8 to 8.4 log10 CFU/mL for
      refrigerated solution and from 1.9 to 8.5 log10 CFU/mL for frozen solution. No
      statistical differences were found between the storage solutions (p > .05). The
      counts of Streptococcus spp., Lactobacillus spp., and Staphylococcus spp. were
      similar for both storage solutions (p > .05). SEM analysis showed spiral- and rod
      shaped bacteria attached on teeth stored under 4  degrees C, which may suggest
      the presence of Treponema spp. and Lactobacillus spp. Similar morphological forms
      were found on teeth stored under -10  degrees C. A biofilm organized in honeycomb
      like form was found in the frozen teeth. Cocci were eventually found in all the
      samples. It was concluded that bacterial growth and survival were not influenced
      by the temperature of the teeth storage solution.

PMID- 29341339
TI  - Immunomodulation By Therapeutic Mesenchymal Stromal Cells (MSC) Is Triggered
      Through Phagocytosis of MSC By Monocytic Cells.
AB  - Mesenchymal stem or stromal cells (MSC) are under investigation as a potential
      immunotherapy. MSC are usually administered via intravenous infusion, after which
      they are trapped in the lungs and die and disappear within a day. The fate of MSC
      after their disappearance from the lungs is unknown and it is unclear how MSC
      realize their immunomodulatory effects in their short lifespan. We examined
      immunological mechanisms determining the fate of infused MSC and the
      immunomodulatory response associated with it. Tracking viable and dead human
      umbilical cord MSC (ucMSC) in mice using Qtracker beads (contained in viable
      cells) and Hoechst33342 (staining all cells) revealed that viable ucMSC were
      present in the lungs immediately after infusion. Twenty-four hours later, the
      majority of ucMSC were dead and found in the lungs and liver where they were
      contained in monocytic cells of predominantly non-classical Ly6Clow phenotype.
      Monocytes containing ucMSC were also detected systemically. In vitro experiments
      confirmed that human CD14++ /CD16- classical monocytes polarized toward a non
      classical CD14++ CD16+ CD206+ phenotype after phagocytosis of ucMSC and expressed
      programmed death ligand-1 and IL-10, while TNF-alpha was reduced. ucMSC-primed
      monocytes induced Foxp3+ regulatory T cell formation in mixed lymphocyte
      reactions. These results demonstrate that infused MSC are rapidly phagocytosed by
      monocytes, which subsequently migrate from the lungs to other body sites.
      Phagocytosis of ucMSC induces phenotypical and functional changes in monocytes,
      which subsequently modulate cells of the adaptive immune system. It can be
      concluded that monocytes play a crucial role in mediating, distributing, and
      transferring the immunomodulatory effect of MSC. Stem Cells 2018;36:602-615.

PMID- 29341340
TI  - Bias from restricting to live births when estimating effects of prescription drug
      use on pregnancy complications: A simulation.
AB  - PURPOSE: Administrative claim databases are increasingly being used to study the
      safety of medication exposures during pregnancy. These studies are restricted to
      live births due to a reliance on algorithms for estimating gestational age that
      are based on codes associated with live delivery. Conditioning on live birth may
      induce selection bias when studying the effect of a drug on a pregnancy
      complication if fetal death is a competing risk for the complication or is caused
      by the complication. METHODS: We simulated a population of 100,000 pregnancies
      and estimated the impact of selection bias on relative estimates for the effect
      of antidepressant exposure on the outcome of preeclampsia. We assumed that the
      exposure, outcome, and covariates increased the risk of fetal loss. RESULTS: A
      downward bias in the risk ratio was consistently observed when conditioning on
      live births. When an unmeasured covariate was assumed to be a common cause of
      fetal death, antidepressant use, and preeclampsia, the direction of bias varied
      depending on the strength of the confounding relationship coupled with the
      selection bias. Despite the very low prevalence of stillbirth, the strength of
      the relationship between antidepressant use and stillbirth had a substantial
      impact on bias. CONCLUSIONS: Conditioning on live birth can be problematic when
      studying pregnancy complications. Simple quantitative selection bias analysis in
      populations restricted to live births may not fully account for selection bias.

PMID- 29341341
TI  - Prediction of activation patterns preceding hallucinations in patients with
      schizophrenia using machine learning with structured sparsity.
AB  - Despite significant progress in the field, the detection of fMRI signal changes
      during hallucinatory events remains difficult and time-consuming. This article
      first proposes a machine-learning algorithm to automatically identify resting
      state fMRI periods that precede hallucinations versus periods that do not. When
      applied to whole-brain fMRI data, state-of-the-art classification methods, such
      as support vector machines (SVM), yield dense solutions that are difficult to
      interpret. We proposed to extend the existing sparse classification methods by
      taking the spatial structure of brain images into account with structured
      sparsity using the total variation penalty. Based on this approach, we obtained
      reliable classifying performances associated with interpretable predictive
      patterns, composed of two clearly identifiable clusters in speech-related brain
      regions. The variation in transition-to-hallucination functional patterns not
      only from one patient to another but also from one occurrence to the next (e.g.,
      also depending on the sensory modalities involved) appeared to be the major
      difficulty when developing effective classifiers. Consequently, second, this
      article aimed to characterize the variability within the prehallucination
      patterns using an extension of principal component analysis with spatial
      constraints. The principal components (PCs) and the associated basis patterns
      shed light on the intrinsic structures of the variability present in the dataset.
      Such results are promising in the scope of innovative fMRI-guided therapy for
      drug-resistant hallucinations, such as fMRI-based neurofeedback.

PMID- 29341342
TI  - The Pentagonal-Pyramidal Hexamethylbenzene Dication: Many Shades of Coordination
      Chemistry at Carbon.
AB  - A recent report on the crystal structure of the pentagonal-pyramidal
      hexamethylbenzene dication C6 (CH3 )62+ by Malischewski and Seppelt [Angew. Chem.
      Int. Ed. 2017, 56, 368] confirmed the structural proposal made in the first
      report of this compound in 1973 by Hogeveen and Kwant [Tetrahedron Lett. 1973,
      14, 1665]. The widespread attention that this compound quickly gained led us to
      reinvestigate its electronic structure. On the basis of intrinsic bond orbital
      analysis, effective oxidation state analysis, ring current analysis, and
      comparison with well-established coordination complexes, it is demonstrated that
      the central carbon atom behaves like a transition metal. The central (apical)
      carbon atom, although best described as a highly Lewis-acidic carbon atom
      coordinated with an anionic cyclopentadienyl ligand, is also capable of acting as
      an electron-pair donor to a formal CH3+ group. The different roles of
      coordination chemistry are discussed.

PMID- 29341343
TI  - Small heat shock protein B3 (HSPB3) mutation in an axonal Charcot-Marie-Tooth
      disease family.
AB  - Heat shock protein B3 (HSPB3) gene encodes a small heat-shock protein 27-like
      protein which has a high sequence homology with HSPB1. A mutation in the HSPB3
      was reported as the putative underlying cause of distal hereditary motor
      neuropathy 2C (dHMN2C) in 2010. We identified a heterozygous mutation (c.352T>C,
      p.Tyr118His) in the HSPB3 from a Charcot-Marie-Tooth disease type 2 (CMT2) family
      by the method of targeted next generation sequencing. The mutation was located in
      the well conserved alpha-crystalline domain, and several in silico predictions
      indicated a pathogenic effect of the mutation. Clinical and electrophysiological
      features of the patients indicated the axonal type of CMT. Clinical symptoms
      without sensory involvements were similar between the present family and the
      previous family. Mutations in the HSPB1 and HSPB8 genes have been reported to be
      relevant with both types of CMT2 and dHMN. Our findings will help in the
      molecular diagnosis of CMT2 by expanding the phenotypic range due to the HSPB3
      mutations.

PMID- 29341344
TI  - The medial temporal lobe functional connectivity patterns associated with forming
      different mental representations.
AB  - The medial temporal lobes (MTL), and more specifically the hippocampus, are
      critical for forming mental representations of past experiences-autobiographical
      memories-and for forming other "nonexperienced" types of mental representations,
      such as imagined scenarios. How the MTL coordinate with other brain areas to
      create these different types of representations is not well understood. To
      address this issue, we performed a task-based functional connectivity analysis on
      a previously published dataset in which fMRI data were collected as participants
      created different types of mental representations under three conditions. One
      condition required forming and relating together details from a past event
      (autobiographical task), another required forming and relating together details
      of a spatial context (spatial task) and another condition required relating
      together conceptual/perceptual features of an object (conceptual task). We
      contrasted the connectivity patterns associated with a functionally defined
      region in the parahippocampal cortex (PHC) and anatomically defined anterior and
      posterior hippocampal segments across these tasks. Examining PHC connectivity
      patterns revealed that the PHC seed was distinctly connected to other MTL
      structures during the autobiographical task, to posterior parietal regions during
      the spatial task and to a distributed network of regions for the conceptual task.
      Examining hippocampal connectivity patterns revealed that the anterior
      hippocampus was preferentially connected to regions of default mode network
      during the autobiographical task and to areas implicated in semantic processing
      for the conceptual task whereas the posterior hippocampus was preferentially
      connected to medial-posterior regions of the brain during the spatial task. We
      interpret our findings as evidence that there are MTL-guided networks for forming
      distinct types of mental representations that align with functional distinctions
      within the hippocampus.

PMID- 29341345
TI  - Increase in neutrophils after recombinant tissue plasminogen activator
      thrombolysis predicts poor functional outcome of ischaemic stroke: a longitudinal
      study.
AB  - BACKGROUND AND PURPOSE: Neutrophils, a pivotal immune responder to ischaemic
      brain insult, have been involved in neuroplasticity and increase after stroke.
      Recombinant tissue plasminogen activator (r-tPA), a promising treatment improving
      neuroplasticity, promotes neutrophil degranulation. However, the dynamic profile
      of neutrophils after r-tPA treatment and their effect on neurological recovery
      after stroke are not well studied. METHODS: Cell counts of neutrophils,
      lymphocytes and their ratio (NLR) were measured on admission and 24 h after r-tPA
      infusion in 372 consecutively recruited acute ischaemic stroke patients (mean age
      64 years). Death or major disability at 3 months after stroke was diagnosed based
      on the modified Rankin Scale (mRS >= 3) obtained by neurologists who were blinded
      to any hospital records. The longitudinal associations of percentage increase in
      neutrophils, lymphocytes and the NLR with death or major disability were examined
      by logistic regression adjusting for covariates including neurological deficits
      at baseline. RESULTS: Neutrophils exhibited a steeper increase after r-tPA
      infusion in patients with death or major disability than in those without (P <
      0.001). A 10% increase in neutrophils after r-tPA infusion was associated with an
      83% increased risk for death or major disability within 3 months after stroke
      onset [odds ratio (OR) 1.99, P = 0.009]. Increased neutrophils at 24 h after r
      tPA (OR 6.30, P < 0.001 after log transformation) but not on admission
      significantly predicted increased risks for death or major disability within 3
      months after stroke onset. A similar phenomenon was also observed for the NLR.
      CONCLUSIONS: A dynamic increase in neutrophils after stroke significantly
      predicts 3-month death or major disability in acute ischaemic stroke patients
      receiving r-tPA treatment.

PMID- 29341346
TI  - A systematic review and classification of interventions for speech-sound disorder
      in preschool children.
AB  - BACKGROUND: Multiple interventions have been developed to address speech sound
      disorder (SSD) in children. Many of these have been evaluated but the evidence
      for these has not been considered within a model which categorizes types of
      intervention. The opportunity to carry out a systematic review of interventions
      for SSD arose as part of a larger scale study of interventions for primary speech
      and language impairment in preschool children. AIMS: To review systematically the
      evidence for interventions for SSD in preschool children and to categorize them
      within a classification of interventions for SSD. METHODS & PROCEDURES: Relevant
      search terms were used to identify intervention studies published up to 2012,
      with the following inclusion criteria: participants were aged between 2 years and
      5 years, 11 months; they exhibited speech, language and communication needs; and
      a primary outcome measure of speech was used. Studies that met inclusion criteria
      were quality appraised using the single case experimental design (SCED) or PEDro
      P, depending on their methodology. Those judged to be high quality were
      classified according to the primary focus of intervention. OUTCOMES & RESULTS:
      The final review included 26 studies. Case series was the most common research
      design. Categorization to the classification system for interventions showed that
      cognitive-linguistic and production approaches to intervention were the most
      frequently reported. The highest graded evidence was for three studies within the
      auditory-perceptual and integrated categories. CONCLUSIONS & IMPLICATIONS: The
      evidence for intervention for preschool children with SSD is focused on seven out
      of 11 subcategories of interventions. Although all the studies included in the
      review were good quality as defined by quality appraisal checklists, they mostly
      represented lower-graded evidence. Higher-graded studies are needed to understand
      clearly the strength of evidence for different interventions.

PMID- 29341347
TI  - Employing the arts for knowledge production and translation: Visualizing new
      possibilities for women speaking up about safety concerns in maternity.
AB  - OBJECTIVES: This project used animated film to translate research findings into
      accessible health information aimed at enabling women to speak up and secure
      professional help for serious safety concerns during pregnancy and after birth.
      We tested as proof of concept our use of the arts both as product (knowledge
      production) and process (enabling involvement). BACKGROUND: Emergencies during
      pregnancy and birth, while unusual, can develop rapidly and unexpectedly, with
      catastrophic consequences. Women's tacit knowledge of changes in their condition
      is an important resource to aid early detection, but women can worry about the
      legitimacy of their concerns and struggle to get these taken seriously by staff.
      DESIGN: Arts-based knowledge translation. A user group of women who had
      experienced complications in the perinatal period (n = 34) helped us develop and
      pilot test the animation. Obstetricians and midwives (15), clinical leads (3) and
      user group representatives (8) helped with the design and testing. FINDINGS: The
      consultation process, script and storyboard enabled active interaction with the
      evidence, meaningful engagement with stakeholders and new understandings about
      securing help for perinatal complications. The method enabled us to address
      gender stereotypes and social norms about speaking up and embed a social script
      for women within the animation, to help structure their help seeking. While for
      some women, there was an emotional burden, the majority were glad to have been
      part of the animation's development and felt it had enabled their voices to be
      heard. CONCLUSION: This project has demonstrated the benefits of arts-science
      collaborations for meaningful co-production and effective translation of research
      evidence.

PMID- 29341348
TI  - The development and validation of the Evidence-Based Practice Questionnaire:
      Japanese version.
AB  - AIM: To develop and test the validity and reliability of a Japanese version of
      the Evidence-Based Practice Questionnaire. METHODS: The Evidence-Based Practice
      Questionnaire was translated into Japanese, and a back-translation was performed.
      In March 2016, the survey was conducted among 843 nurses in 2 university
      hospitals in Japan. After 2 weeks, the same questionnaire for test-retest
      reliability was distributed to 197 nurses. We evaluated construct validity by
      factor analysis: convergent, discriminant, criterion-based and known-group
      validity, and reliability (internal consistency via Cronbach' alpha and test
      retest reliability). RESULTS: A total of 533 (66%) of nurses who agreed to our
      study returned the completed questionnaire, and 108 nurses (55%) agreed to the
      test-retest. Factor analysis confirmed that the original model of the Evidence
      Based Practices Questionnaire was not statistically appropriate for Japanese
      nurses. Therefore, the final version of the Japanese version adopted 18 items and
      4 subscales including practice, attitudes, and knowledge/skills related to
      research and practice. In the final version, the validity and reliability were
      moderate (Cronbach alpha = .90). CONCLUSION: The Japanese version of the Evidence
      Based Practices Questionnaire is a reliable and valid tool and can be used to
      assess evidence-based practice, attitudes, and research knowledge/skills in
      Japan.

PMID- 29341349
TI  - Peroxiredoxin 4 (PRDX4): Its critical in vivo roles in animal models of metabolic
      syndrome ranging from atherosclerosis to nonalcoholic fatty liver disease.
AB  - The peroxiredoxin (PRDX) family, a new family of proteins with a pivotal
      antioxidative function, is ubiquitously synthesized and abundantly identified in
      various organisms. In contrast to the intracellular localization of other family
      members (PRDX1/2/3/5/6), PRDX4 is the only known secretory form and protects
      against oxidative damage by scavenging reactive oxygen species in both the
      intracellular (especially the endoplasmic reticulum) compartments and the
      extracellular space. We generated unique human PRDX4 (hPRDX4) transgenic (Tg)
      mice on a C57BL/6J background and investigated the critical and diverse
      protective roles of PRDX4 against diabetes mellitus, atherosclerosis, insulin
      resistance, and nonalcoholic fatty liver disease (NAFLD) as well as evaluated its
      role in the intestinal function in various animal models. Our published data have
      shown that PRDX4 helps prevent the progression of metabolic syndrome by reducing
      local and systemic oxidative stress and synergistically suppressing steatosis,
      inflammatory reactions, and/or apoptotic activity. These observations suggest
      that Tg mice may be a useful animal model for studying the relevance of oxidative
      stress on inflammation and the dysregulation of lipid/bile acid/glucose
      metabolism upon the progression of human metabolic syndrome, and that specific
      accelerators of PRDX4 may be useful as therapeutic agents for ameliorating
      various chronic inflammatory diseases.

PMID- 29341350
TI  - The effects of wireless electromagnetic fields on the activities of carbonic
      anhydrase and acetylcholinesterase enzymes in various tissues of rats.
AB  - The purpose of our study is to assist in understanding the effects of wireless
      electromagnetic waves on carbonic anhydrase (CA) and acetylcholinesterase (AChE)
      enzymes activities in the different tissues of the rats. For this purpose, two
      different groups each of which contains eight rats (n = 8) were formed as being
      control group and wireless electromagnetic wave-administered group. The rats were
      necropsied after 60 min from the injection of chemicals into the rats
      intraperitoneally. The different tissues of the rats were extracted. CA and AChE
      enzymes activities were measured for each tissue. All the experimental results
      were provided in mean +/- S.D. Statistical significance was identified to be P <
      0.05. It was observed that there were significant changes of enzyme activities in
      wireless-administered group in salivary gland, stomach, colon, liver, and
      striated muscle tissues.

PMID- 29341351
TI  - Discordant von Willebrand factor (VWF) activity in patients with VWF p.Gly1324Ser
      confirmed in vitro.

PMID- 29341352
TI  - Misregulation of membrane trafficking processes in human nonalcoholic
      steatohepatitis.
AB  - Nonalcoholic steatohepatitis (NASH) remodels the expression and function of genes
      and proteins that are critical for drug disposition. This study sought to
      determine whether disruption of membrane protein trafficking pathways in human
      NASH contributes to altered localization of multidrug resistance-associated
      protein 2 (MRP2). A comprehensive immunoblot analysis assessed the
      phosphorylation, membrane translocation, and expression of transporter membrane
      insertion regulators, including several protein kinases (PK), radixin, MARCKS,
      and Rab11. Radixin exhibited a decreased phosphorylation and total expression,
      whereas Rab11 had an increased membrane localization. PKCdelta, PKCalpha, and PKA
      had increased membrane activation, whereas PKCepsilon had a decreased
      phosphorylation and membrane expression. Radixin dephosphorylation may activate
      MRP2 membrane retrieval in NASH; however, the activation of Rab11/PKCdelta and
      PKA/PKCalpha suggest an activation of membrane insertion pathways as well.
      Overall these data suggest an altered regulation of protein trafficking in human
      NASH, although other processes may be involved in the regulation of MRP2
      localization.

PMID- 29341353
TI  - Fluorescence Redox Blinking Adaptable to Structural Analysis of Nucleic Acids.
AB  - The phenomenon of blinking is unique to single-molecule fluorescence
      measurements. By designing a fluorophore with an appropriate dark-state lifetime
      tauoff , a kinetic analysis based on the control of fluorescence blinking (KACB)
      was devised to investigate the dynamics of biomolecules. By controlling the redox
      reaction-based blinking (rKACB), conformational dynamics of RNA at the single
      molecule level was previously investigated. However, there is little knowledge
      about suitable fluorescent molecules for rKACB, and the application of rKACB has
      been limited to the analysis of hairpins and duplex structures of nucleic acids.
      In this work, various fluorescent molecules, including Alexa 488, R6G, TAMRA,
      ATTO 647N and ATTO 655, were evaluated for rKACB. Moreover, rKACB was adapted to
      the discrimination of DNA/DNA and DNA/RNA nucleic acid duplexes and investigation
      of antigen-antibody interactions. By changing the size of the oxidant, it was
      possible to determine the solvent accessibility of the target domain of the
      analyzed biomolecules.

PMID- 29341354
TI  - A mutation in the heptad repeat 2 domain of MFN2 in a large CMT2A family.
AB  - Dominant mutations in MFN2 cause a range of phenotypes, including severe, early
      onset axonal neuropathy, "classical CMT2," and late-onset axonal neuropathies. We
      report a large family with an axonal polyneuropathy, with clinical onset in the
      20s, followed by slow progression.

PMID- 29341355
TI  - Reflectance confocal microscopy and optical coherence tomography for the
      diagnosis of bullous pemphigoid and pemphigus and surrounding subclinical
      lesions.
AB  - BACKGROUND: Diagnosis of bullous pemphigoid (BP) and pemphigus is based on
      clinical features, histology, immunofluorescence and laboratory data. OBJECTIVES:
      To evaluate features of BP and pemphigus at reflectance confocal microscopy (RCM)
      and optical coherence tomography (OCT) in order to provide a rapid non-invasive
      bed-side diagnosis. Secondary objective was to evaluate the detectability of
      clinically non-visible lesions. METHODS: This was an observational,
      retrospective, multicentre study in which patients with suspicious lesions for BP
      or pemphigus underwent clinical assessment, RCM, OCT, blood tests and skin biopsy
      for histological and direct immunofluorescence examinations from January 2014 to
      December 2015. A total of 72 lesions in 24 selected patients were evaluated.
      Additionally, apparently unaffected skin at two different distances [near (1-2
      cm) and far (2-3 cm)] from each lesion was examined to test subclinical lesion
      detectability. RESULTS: RCM was able to detect subepidermal and intra-epidermal
      blisters, respectively, in 75% and 50% of the patients affected by BP and
      pemphigus. At OCT, the exact blister level was identified in all patients.
      Acantholytic cells were observed only at RCM in pemphigus (62.5%). Fibrin
      deposition inside the blisters was only found in BP, evidenced both at RCM and
      OCT. Among patients with BP, subclinical blisters were detected in nine (9.4%)
      clinically healthy skin, while among patients with pemphigus were observed in 10
      (20.8%) apparently unaffected skin. CONCLUSION: RCM and/or OCT provide useful
      information for a rapid diagnosis of BP and pemphigus and for the identification
      of biopsy site. Combined use of RCM and OCT is optimal because associates the
      higher resolution of RCM with the greater penetration depth of OCT. OCT could be
      an optimal tool for treatment monitoring, especially in the cases of subclinical
      lesions. However, histopathologic and immunologic examinations remain the gold
      standard for establishing the final diagnosis.

PMID- 29341356
TI  - All over the map: An interobserver agreement study of tumor location based on the
      PI-RADSv2 sector map.
AB  - BACKGROUND: Prostate imaging reporting and data system version 2 (PI-RADSv2)
      recommends a sector map for reporting findings of prostate cancer mulitparametric
      MRI (mpMRI). Anecdotally, radiologists may demonstrate inconsistent
      reproducibility with this map. PURPOSE: To evaluate interobserver agreement in
      defining prostate tumor location on mpMRI using the PI-RADSv2 sector map. STUDY
      TYPE: Retrospective. POPULATION: Thirty consecutive patients who underwent mpMRI
      between October, 2013 and March, 2015 and who subsequently underwent
      prostatectomy with whole-mount processing. FIELD STRENGTH: 3T mpMRI with T2 W,
      diffusion-weighted imaging (DWI) (apparent diffusion coefficient [ADC] and b
      2000), dynamic contrast-enhanced (DCE). ASSESSMENT: Six radiologists (two high,
      two intermediate, and two low experience) from six institutions participated.
      Readers were blinded to lesion location and detected up to four lesions as per PI
      RADSv2 guidelines. Readers marked the long-axis of lesions, saved screen-shots of
      each lesion, and then marked the lesion location on the PI-RADSv2 sector map.
      Whole-mount prostatectomy specimens registered to the MRI served as ground truth.
      Index lesions were defined as the highest grade lesion or largest lesion if
      grades were equivalent. STATISTICAL TEST: Agreement was calculated for the exact,
      overlap, and proportion of agreement. RESULTS: Readers detected an average of 1.9
      lesions per patient (range 1.6-2.3). 96.3% (335/348) of all lesions for all
      readers were scored PI-RADS >=3. Readers defined a median of 2 (range 1-18)
      sectors per lesion. Agreement for detecting index lesions by screen shots was
      83.7% (76.1%-89.9%) vs. 71.0% (63.1-78.3%) overlap agreement on the PI-RADS
      sector map (P < 0.001). Exact agreement for defining sectors of detected index
      lesions was only 21.2% (95% confidence interval [CI]: 14.4-27.7%) and rose to
      49.0% (42.4-55.3%) when overlap was considered. Agreement on defining the same
      level of disease (ie, apex, mid, base) was 61.4% (95% CI 50.2-71.8%). DATA
      CONCLUSION: Readers are highly likely to detect the same index lesion on mpMRI,
      but exhibit poor reproducibility when attempting to define tumor location on the
      PI-RADSv2 sector map. The poor agreement of the PI-RADSv2 sector map raises
      concerns its utility in clinical practice. LEVEL OF EVIDENCE: 3 Technical
      Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2018;48:482-490.

PMID- 29341357
TI  - A multicenter pilot survey to clarify the clinical features of patients with
      acute-on-chronic liver failure in Japan.
AB  - AIM: To establish diagnostic criteria for acute-on-chronic liver failure (ACLF)
      in Japan, a multicenter pilot survey was carried out to examine the usefulness of
      overseas criteria in patients with chronic liver diseases manifesting acute
      decompensation. METHODS: Patients fulfilling the Asian-Pacific Association for
      the Study of the Liver (APASL), European Association for the Study of the Liver
      (EASL), or Chinese Medical Association (CMA) criteria for decompensation were
      enrolled from eight institutions in Japan, and the clinical features were
      evaluated. RESULTS: Among 112 patients, 109 patients (97.3%) fulfilled the APASL
      criteria for decompensation; 7 patients were excluded because the decompensation
      had been provoked by gastrointestinal bleeding. Consequently, 102 patients
      (91.1%) were diagnosed as having ACLF according to the APASL definition. Among
      the patients who fulfilled the APASL criteria for decompensation, the etiologies
      of the underlying liver diseases were alcohol abuse in 59 cases (54.1%) and
      hepatitis B or hepatitis C virus infection in 24 (22.0%). The acute insults were
      alcohol abuse in 50 (45.9%), bacterial infection in 26 (23.9%), and exacerbation
      of underlying liver disease in 14 (12.8%). Fifty-four patients (49.5%) satisfied
      the CMA criteria, but the survival rates were similar between patients who did
      and those who did not meet the criteria. When 84 patients with underlying
      cirrhosis were classified according to the EASL-Chronic Liver Failure (Clif)
      Consortium criteria, the survival rates differed according to grade: 67.6%
      (23/34) for patients without ACLF, and 41.2% (14/34) and 18.8% (3/16) for those
      with grade 1/2 and grade 3 ACLF, respectively. CONCLUSION: The APASL definition
      was suitable for screening Japanese patients with ACLF, including those whose
      conditions were triggered by gastrointestinal bleeding, and the EASL-Clif
      Consortium criteria were useful for predicting outcome.

PMID- 29341358
TI  - Thermal and hydrologic responses to climate change predict marked alterations in
      boreal stream invertebrate assemblages.
AB  - Air temperature at the northernmost latitudes is predicted to increase steeply
      and precipitation to become more variable by the end of the 21st century,
      resulting in altered thermal and hydrological regimes. We applied five climate
      scenarios to predict the future (2070-2100) benthic macroinvertebrate assemblages
      at 239 near-pristine sites across Finland (ca. 1200 km latitudinal span). We used
      a multitaxon distribution model with air temperature and modeled daily flow as
      predictors. As expected, projected air temperature increased the most in
      northernmost Finland. Predicted taxonomic richness also increased the most in
      northern Finland, congruent with the predicted northwards shift of many species'
      distributions. Compositional changes were predicted to be high even without
      changes in richness, suggesting that species replacement may be the main
      mechanism causing climate-induced changes in macroinvertebrate assemblages.
      Northern streams were predicted to lose much of the seasonality of their flow
      regimes, causing potentially marked changes in stream benthic assemblages. Sites
      with the highest loss of seasonality were predicted to support future assemblages
      that deviate most in compositional similarity from the present-day assemblages.
      Macroinvertebrate assemblages were also predicted to change more in headwaters
      than in larger streams, as headwaters were particularly sensitive to changes in
      flow patterns. Our results emphasize the importance of focusing protection and
      mitigation on headwater streams with high-flow seasonality because of their
      vulnerability to climate change.

PMID- 29341359
TI  - Familiar communication partners' facilitation of topic management in
      conversations with individuals with dementia.
AB  - BACKGROUND: Language and memory impairments affect everyday interactions between
      individuals with dementia and their communication partners. Impaired topic
      management, which compromises individuals' construction of relevant, meaningful
      discourse, is commonly reported amongst individuals with dementia. Currently,
      limited empirical evidence describes the sequential patterns of behaviour
      comprising topic-management practices in everyday conversation between
      individuals with dementia and their communication partners. AIMS: To describe the
      sequential patterns of behaviour relating to the manifestation of topic
      management impairments and facilitative behaviours in everyday interactions
      between individuals with dementia and their familiar communication partners
      (FCPs). METHODS & PROCEDURES: Three 20-min conversations between individuals with
      moderate to severe dementia and their FCPs were recorded. Conversation Analysis
      was used to examine sequences in which topic-management appeared to be impaired.
      OUTCOMES & RESULTS: Conversational behaviours that reflected a difficulty in
      contributing on-topic talk were pervasive in the talk of the three individuals
      with dementia. FCPs responded to these conversational difficulties by using two
      categories of facilitative behaviours. The first involved responding to an
      individual with dementia's explicit repair-initiation by performing repair. In
      the second category, explicit repair-initiation was absent; instead, the distance
      of the conversational difficulty from the prior topic-shifting turn mediated the
      form and outcome of the FCPs' facilitative behaviours. Each category successfully
      facilitated the individual with dementia to contribute on-topic talk. CONCLUSIONS
      & IMPLICATIONS: The findings contribute to a growing understanding of topic
      management abilities in everyday interactions involving individuals with
      dementia. Individuals with dementia took a proactive role in eliciting topic
      management support. The FCPs responded with turns that facilitated the
      individuals with dementia to talk on-topic. Clinically, the results support and
      extend the current topic-management recommendations available in communication
      partner training programmes, and promote conversations which attend to the
      personhood of the individual with dementia.

PMID- 29341360
TI  - Comparison of respiratory system impedance in asthma and COPD: A prospective
      observational study.
AB  - BACKGROUND AND OBJECTIVE: A single assessment of within-breath variations of
      respiratory system reactance (Xrs) at 5 Hz (DeltaX5) measured by the forced
      oscillation technique (FOT) has been reported to be useful for the detection of
      pathophysiological changes in chronic obstructive pulmonary disease (COPD) and
      asthma. We examined longitudinal changes in respiratory system resistance (Rrs)
      and Xrs during tidal breathing between stable asthma and COPD patients in order
      to clarify the features of changes of respiratory system impedance and airflow
      limitation for these conditions. METHODS: Between April 2013 and September 2013,
      outpatients with a COPD or asthma diagnosis were recruited. We examined forced
      expiratory volume in 1 s (FEV1 ) and FOT every 6 months until September 2015.
      Annual changes were estimated from the linear regression curve slope. RESULTS: We
      included 57 and 93 subjects with COPD and asthma, respectively. The median follow
      up period was 26 months (range: 24-29 months). Within-breath analysis showed that
      the difference between mean Rrs at 5 Hz and 20 Hz was significantly lower, and
      DeltaX5 more negative, in COPD than in asthma patients. With regard to annual
      changes, only DeltaX5 was significantly different, more negative, in COPD than in
      asthma patients. Comparing between COPD subjects of Global Initiative Chronic
      Obstructive Lung Disease (GOLD) stage I/II and those with asthma, there were no
      significant differences in respiratory system impedance at enrolment, while
      annual change in DeltaX5 was significantly more negative in mild COPD than in
      asthma patients. CONCLUSION: DeltaX5 may be useful for long-term assessment of
      airflow limitation in COPD.

PMID- 29341362
TI  - A novel mutation of LRSAM1 in a Chinese family with Charcot-Marie-Tooth disease.
AB  - Charcot-Marie-Tooth (CMT) disease is the most common inherited peripheral
      neuropathy characterized by progressive distal muscle weakness and atrophy with
      decreased or absent tendon reflexes. Mutations in LRSAM1 have been identified to
      cause CMT disease type 2P. We report a novel LRSAM1 mutation c.2021-2024del
      (p.E674VfsX11) in a Chinese autosomal dominant CMT disease type 2 family. The
      phenotype was characterized by late onset and mild sensory impairment.
      Electrophysiological findings showed normal or mildly to moderately reduced motor
      and sensory nerve conduction velocities in lower and upper limb nerves.

PMID- 29341361
TI  - Parvalbumin interneuron mediated feedforward inhibition controls signal output in
      the deep layers of the perirhinal-entorhinal cortex.
AB  - The perirhinal (PER) and lateral entorhinal (LEC) cortex form an anatomical link
      between the neocortex and the hippocampus. However, neocortical activity is
      transmitted through the PER and LEC to the hippocampus with a low probability,
      suggesting the involvement of the inhibitory network. This study explored the
      role of interneuron mediated inhibition, activated by electrical stimulation in
      the agranular insular cortex (AiP), in the deep layers of the PER and LEC.
      Activated synaptic input by AiP stimulation rarely evoked action potentials in
      the PER-LEC deep layer excitatory principal neurons, most probably because the
      evoked synaptic response consisted of a small excitatory and large inhibitory
      conductance. Furthermore, parvalbumin positive (PV) interneurons-a subset of
      interneurons projecting onto the axo-somatic region of principal neurons-received
      synaptic input earlier than principal neurons, suggesting recruitment of
      feedforward inhibition. This synaptic input in PV interneurons evoked varying
      trains of action potentials, explaining the fast rising, long lasting synaptic
      inhibition received by deep layer principal neurons. Altogether, the excitatory
      input from the AiP onto deep layer principal neurons is overruled by strong
      feedforward inhibition. PV interneurons, with their fast, extensive stimulus
      evoked firing, are able to deliver this fast evoked inhibition in principal
      neurons. This indicates an essential role for PV interneurons in the gating
      mechanism of the PER-LEC network.

PMID- 29341364
TI  - Food-dependent exercise-induced anaphylaxis in Japanese elementary school
      children.
AB  - BACKGROUND: In 2012, we clarified that the prevalence of food-dependent exercise
      induced anaphylaxis (FDEIA) was 0.018% in junior-high students in Yokohama,
      Japan. Furthermore, although different from FDEIA, one student who had completed
      oral immunotherapy developed anaphylaxis during exercise after eating causative
      food. There have been few large-scale epidemiological studies of FDEIA, however,
      in elementary school children, therefore we conducted an epidemiological study in
      elementary school children in Yokohama to clarify the frequency and
      characteristic of FDEIA. METHODS: We sent a questionnaire regarding the
      occurrence of FDEIA to all 348 public elementary school nurses in Yokohama. We
      also compared the results with those for junior-high school that we previously
      reported. We excluded those children with a past history of immediate food
      allergy who had achieved desensitization status after oral immunotherapy, from
      FDEIA, and instead defined them as having desensitization status and exercise
      induced anaphylaxis (DEIA). RESULTS: Of 348 school nurses, 317 responded (91.1%).
      Overall, eight of 170 146 children were diagnosed with FDEIA, which was
      significantly lower than the prevalence in junior-high school students (0.0047%
      vs 0.018%, P = 0.0009). The causative foods were wheat (n = 4), and soy, fruit,
      crustaceans, and squid (n = 1 each). Four children had DEIA and the causative
      foods were wheat and milk (n = 2 each). Multiple episodes occurred in five
      children with FDEIA and in three children with DEIA. CONCLUSIONS: FDEIA was far
      less common in elementary school than in junior-high school, and wheat was the
      major causative food. The new appearance of DEIA was notable. Decreasing episode
      recurrence remains an issue that needs to be resolved.

PMID- 29341365
TI  - How and Why Does Helium Permeate Nonporous Arsenolite Under High Pressure?
AB  - Investigations into the helium permeation of arsenolite, the cubic, molecular
      arsenic(III) oxide polymorph As4 O6 , were carried out to understand how and why
      arsenolite helium clathrate As4 O6 ?2 He is formed. High-pressure synchrotron X
      ray diffraction experiments on arsenolite single crystals revealed that the
      permeation of helium into nonporous arsenolite depends on the time for which the
      crystal is subjected to high pressure and on the crystal history. The single
      crystal was totally transformed into As4 O6 ?2 He within 45 h under 5 GPa. After
      release of the pressure, arsenolite was recovered and a repeated increase in
      pressure up to 3 GPa led to practically instant As4 O6 ?2 He formation. However,
      when a pristine arsenolite single crystal was quickly subjected to a pressure of
      13 GPa, no helium permeation was observed at all. No neon permeation was observed
      in analogous experiments. Quantum mechanical computations indicate that there are
      no specific attractive interactions between He atoms and As4 O6 molecules at the
      distances observed in the As4 O6 ?2 He crystal structure. Detailed analysis of
      As4 O6 molecular structure changes has shown that the introduction of He into the
      arsenolite crystal lattice significantly reduces molecular deformations by
      decreasing the anisotropy of stress exerted on the As4 O6 molecules. This effect
      and the pDeltaV term, rather than any specific As???He binding, are the driving
      forces for the formation As4 O6 ?2 He.

PMID- 29341366
TI  - Impact of multiple stressors on juvenile fish in estuaries of the northeast
      Pacific.
AB  - A key step in identifying global change impacts on species and ecosystems is to
      quantify effects of multiple stressors. To date, the science of global change has
      been dominated by regional field studies, experimental manipulation, meta
      analyses, conceptual models, reviews, and studies focusing on a single stressor
      or species over broad spatial and temporal scales. Here, we provide one of the
      first studies for coastal systems examining multiple stressor effects across
      broad scales, focused on the nursery function of 20 estuaries spanning 1,600 km
      of coastline, 25 years of monitoring, and seven fish and invertebrate species
      along the northeast Pacific coast. We hypothesized those species most estuarine
      dependent and negatively impacted by human activities would have lower presence
      and abundances in estuaries with greater anthropogenic land cover, pollution, and
      water flow stress. We found significant negative relationships between juveniles
      of two of seven species (Chinook salmon and English sole) and estuarine
      stressors. Chinook salmon were less likely to occur and were less abundant in
      estuaries with greater pollution stress. They were also less abundant in
      estuaries with greater flow stress, although this relationship was marginally
      insignificant. English sole were less abundant in estuaries with greater land
      cover stress. Together, we provide new empirical evidence that effects of
      stressors on two fish species culminate in detectable trends along the northeast
      Pacific coast, elevating the need for protection from pollution, land cover, and
      flow stressors to their habitats. Lack of response among the other five species
      could be related to differing resistance to specific stressors, type and
      precision of the stressor metrics, and limitations in catch data across estuaries
      and habitats. Acquiring improved measurements of impacts to species will guide
      future management actions, and help predict how estuarine nursery functions can
      be optimized given anthropogenic stressors and climate change scenarios.

PMID- 29341367
TI  - Development of Antibody-Directed Therapies: Quo Vadis?
AB  - Less is more: The efficacy of antibody-drug conjugates (ADCs) for cancer therapy
      is traditionally associated with cleavable linkers for payload release. Evidence
      now suggests that simpler constructs without cleavable moieties can afford more
      stable and effective ADCs.

PMID- 29341368
TI  - Multiple sclerosis as a universal disease and the challenges to immigrants in
      high prevalence countries.

PMID- 29341369
TI  - Structural Factors Affecting Binding of Platinum Anticancer Agents with
      Phospholipids: Influence of Charge and Phosphate Clamp Formation.
AB  - We report a detailed NMR and DFT study of the interaction of polynuclear platinum
      anticancer agents (PPCs) with negatively charged phospholipids as a mechanism for
      their cellular uptake. The reactions of fully 15 N-labelled [{trans-PtCl(NH3 )2
      }2 (MU-trans-Pt(NH3 )2 {NH2 (CH2 )6 NH2 }2 )]4+ (15 N-1, 1,0,1/t,t,t) and the
      dinuclear [{trans-PtCl(NH3 )2 }2 {MU-H2 N(CH2 )6 NH2 }]2+ (15 N-2, 1,1/t,t) with
      the sodium salt of 1,2-dihexanoyl-sn-glycero-3-phosphate (DHPA) were studied at
      298 K, pH ~5.4, by [1 H,15 N] HSQC 2D NMR spectroscopy. Both 15 N-1 and 15 N-2
      form an initial mono-adduct in which the DHPA is coordinated via the phosphate O
      atom. For the dinuclear 15 N-2, coordination of a second DHPA, in two different
      orientations, leads to two conformers of the bifunctional adduct. For 15 N-1,
      coordination of the second DHPA allows the central {PtN4 } coordination unit to
      bind electrostatically to two additional DHPA molecules via phosphate clamp
      interactions, in an extended network. For both 1,0,1/t,t,t (1) and 1,1/t,t (2),
      equilibrium conditions are obtained more slowly (>35 h) than in the presence of
      phosphate (12 h) and in each case the rate constant for the first step of DHPA
      binding (kL ) is about 8 times higher than that for phosphate, whereas the rate
      constants for the reverse reactions are quite similar. Reaction of 15 N-1 with
      the sodium salt of 1,2-dihexanoyl-sn-glycero-3-[phosphatidyl-l-serine] (DHPS)
      showed only minor adduct formation via coordination to the N-donor atom of the
      phosphoserine group.

PMID- 29341370
TI  - Real-world clinical outcomes and predictors of glycaemic and weight response to
      exenatide once weekly in patients with type 2 diabetes: The CIBELES project.
AB  - AIMS: To evaluate in a real-world setting the effectiveness of exenatide once
      weekly (ExQW) in patients with T2D and to determine predictors of glycaemic and
      weight response to this drug at 6 months. METHODS: Observational, retrospective,
      multicenter study in adult patients with T2D and BMI >=30 kg/m2 from 4 tertiary
      Spanish hospitals who started ExQW therapy at least 6 months before the inclusion
      and had not achieved adequate glycaemic control on oral therapies or other GLP-1
      receptor agonists. Glycaemic response was defined as an A1C reduction >=1.0% and
      weight response as a weight loss >=3% 6 months after ExQW. The best predictive
      models of glycaemic and weight response were estimated by binary logistic
      regression. RESULTS: One hundred and forty eight patients were included, mean age
      58.0 years, A1C 7.7%, weight 105.9 kg and BMI 38.4 kg/m2 . A1C (-1.1%), weight (
      3.9 kg), systolic blood pressure (-4.0 mm Hg), diastolic blood pressure (-2.9 mm
      Hg), LDL-cholesterol (-14.2 mg/dL) and triglycerides (-31.0 mg/dL) significantly
      decreased 6 months after ExQW. 41.5% of patients had an A1C reduction >=1.0% and
      53.1% lost >=3% of baseline weight. Glycaemic and weight reductions were
      sustained in patients completing 1 and 2 years of follow-up. The best predictive
      model of glycaemic response only included higher A1C levels (OR 3.9), whereas
      higher BMI (OR 1.1) and prior DPP-4i therapy (OR 3.1) were associated to weight
      response in the multivariate analysis. CONCLUSIONS: In a real-world setting, ExQW
      significantly decreased A1C, weight, blood pressure and lipids at 6 months. Our
      study identified higher baseline A1C as the sole independent predictor of
      glycaemic response to ExQW and higher BMI and previous DDP4i treatment as
      predictive factors of meaningful weight response.

PMID- 29341371
TI  - Electrochemical monitoring of aflatoxin M1 in milk samples using silver
      nanoparticles dispersed on alpha-cyclodextrin-GQDs nanocomposite.
AB  - Aflatoxins are potential food pollutants produced by fungi. One of important
      toxins is aflatoxin M1 (AFM1). A great deal of concern is associated with AFM1
      toxicity. In the present study, an innovative electrochemical interface for
      quantitation of AFM1 based on ternary signal amplification strategy was
      fabricated. In this work, silver nanoparticles was electrodeposited onto green
      and biocompatible nanocomposite containing alpha-cyclodextrin as conductive
      matrix and graphene quantum dots as amplification element. Therefore, a
      multilayer film based on alpha-cyclodextrin, graphene quantum dots, and silver
      nanoparticles was exploited to develop a highly sensitive electrochemical sensor
      for detection of AFM1. Fully electrochemical methodology was used to prepare a
      transducer on a glassy carbon electrode, which provided a high surface area
      toward sensitive detection of AFM1. The surface morphology of electrode surface
      was characterized by high-resolution field emission scanning electron microscope.
      The proposed sensing platform provides a simple tool for AFM1 detection. Under
      optimized condition, the calibration curve for AFM1 concentration was linear in
      0.015mM to 25mM with low limit of quantification of 2MUM. The practical
      analytical utility of the modified electrode was illustrated by determination of
      AFM1 in unprocessed milk samples.

PMID- 29341372
TI  - Renal transplantation in children under 3 years of age: Experience from a single
      center study.
AB  - RTx remains challenging in children under 3 years of age. This single-center
      study reviewed the medical records of children <3 years transplanted since 1987
      (N = 32, Group 1). They were matched for donor type and RTx period with children
      aged 3-13 years (N = 32, Group 2) and 13-18 years (N = 32, Group 3). There were
      no between-group significant differences regarding distributions of gender,
      primary renal disease, proportion of dialysis before RTx, and growth (SDS).
      Compared to Groups 2 and 3, Group 1 had more peritoneal dialyses (P < .001), more
      EBV mismatches (P = .04), and longer warm ischemia times (P < .001). The risk of
      graft loss was not significantly different among age groups (hazard ratio, 2.4 in
      Group 2 and 2.0 in Group 3 vs Group 1; P = .2). Death occurred in four patients
      (3 in Group 1 and 1 in Group 2) and graft loss occurred in 28 patients, mainly
      due to chronic allograft nephropathy. In recipients <3 years of age, the outcomes
      of RTx are close to those obtained in older pediatric age groups. Thus, young
      patients may be transplanted in experienced multidisciplinary teams without
      additional risks provided that particular attention is paid to donor selection
      and prevention/early diagnosis of comorbidities and complications.

PMID- 29341373
TI  - Antibiotic allergy labels-the impact of taking a clinical history.
AB  - BACKGROUND: Many patients admitted to hospital have an antibiotic allergy (AAL)
      documented in their medical record. In many of these, the reaction is not a
      hypersensitivity reaction or may no longer be relevant. Despite this, the label
      adversely affects patient care directly in terms of antibiotic selection, and
      indirectly in terms of patient costs and the development of antimicrobial
      resistance. AIMS: To estimate the prevalence of AALs in a cohort of hospitalised
      patients, to investigate the feasibility of de-labelling through re-challenge
      based solely upon clinical grounds. DESIGN: This is a cross-sectional study
      conducted over a 6-month period on adult inpatients. An allergy history was taken
      from each patient and compared with medical record data regarding allergy.
      Antibiotic selection data were collected (if relevant). It was then determined
      whether immediate de-labelling was appropriate, if direct provocation test (DPT)
      could be relatively safely performed, and if antibiotic selection was
      appropriate. RESULTS: Three thousand eight hundred and fifty five patients were
      screened, 553 (14.35%) had an AAL, and 352 were interviewed. There were 426 AALs;
      276 (64.8%) towards a penicillin. After taking a detailed clinical history of the
      type of reaction, approximately 20% could be immediately de-labelled and educated
      (non-allergic, non-severe reactions) and another 38% with either a definite or
      vague history of mild cutaneous reaction would be suitable for an attempt at
      clinical de-labelling DPT. CONCLUSIONS: These simple measures to 'de-label'
      patients appropriately, would increase the quality of care of this group known to
      have higher costs, infection with more resistant bacteria and worse health
      outcomes that 'non-labelled' patients.

PMID- 29341374
TI  - Validation of the digital PCR system in tyrosine kinase inhibitor-resistant EGFR
      mutant non-small-cell lung cancer.
AB  - The aim of this study was to compare the accuracy of the QuantStudio 3D Digital
      polymerase chain reaction (dPCR) system and a PCR-based next generation
      sequencing (NGS) system for detecting a secondary mutation in the epidermal
      growth factor receptor (EGFR) gene T790M in non-small cell lung cancer (NSCLC)
      patients previously diagnosed with EGFR-activating mutations. Twenty-five
      patients with NSCLC previously treated with EGFR-TKIs were examined. The patients
      were treated daily with either erlotinib or gefitinib. New biopsies, followed by
      DNA sequencing on an Ion Torrent systems using the Ion Torrent AmpliSeq Cancer
      Hotspot Panel and dPCR were performed. A comparison of NGS, sensitive PCR, and
      dPCR revealed that the sensitivities of NGS and dPCR were similar in this study.
      As well, T790M was detected in as low as about 5% of mutant allelic frequencies,
      which represented 5% of the total reads on site mapped reads in NGS and greater
      than 5% of the dPCR reads, which represented mutant and wild type copies. The
      strategy in which NGS sequencing is followed by revealed acquired mutation with
      dPCR may be a reasonable one. We demonstrated the utility of combining NGS and
      dPCR as a tool for monitoring T790M. NGS and dPCR with formalin-fixed paraffin
      embedded (FFPE) specimens might become a standard genomic test for exploring
      acquired resistance to targeted molecular medicines.

PMID- 29341375
TI  - Transparency-enhancing technology allows three-dimensional assessment of
      gastrointestinal mucosa: A porcine model.
AB  - Although high-resolution three-dimensional imaging of endoscopically resected
      gastrointestinal specimens can help elucidating morphological features of
      gastrointestinal mucosa or tumor, there are no established methods to achieve
      this without breaking specimens apart. We evaluated the utility of transparency
      enhancing technology for three-dimensional assessment of gastrointestinal mucosa
      in porcine models. Esophagus, stomach, and colon mucosa samples obtained from a
      sacrificed swine were formalin-fixed and paraffin-embedded, and subsequently
      deparaffinized for analysis. The samples were fluorescently stained, optically
      cleared using transparency-enhancing technology: ilLUmination of Cleared organs
      to IDentify target molecules method (LUCID), and visualized using laser scanning
      microscopy. After observation, all specimens were paraffin-embedded again and
      evaluated by conventional histopathological assessment to measure the impact of
      transparency-enhancing procedures. As a result, microscopic observation revealed
      horizontal section views of mucosa at deeper levels and enabled the three
      dimensional image reconstruction of glandular and vascular structures. Besides,
      paraffin-embedded specimens after transparency-enhancing procedures were all
      assessed appropriately by conventional histopathological staining. These results
      suggest that transparency-enhancing technology may be feasible for clinical
      application and enable the three-dimensional structural analysis of endoscopic
      resected specimen non-destructively. Although there remain many limitations or
      problems to be solved, this promising technology might represent a novel
      histopathological method for evaluating gastrointestinal cancers.

PMID- 29341376
TI  - Effects of Playback Theatre on cognitive function and quality of life in older
      adults in Singapore: A preliminary study.
AB  - OBJECTIVE: This study investigated the effects of Playback Theatre on older
      adults' cognitive function and well-being, specifically in the Singapore context.
      METHODS: Eighteen healthy older adults, older than 50 years of age, participated
      in the study. Due to practical limitations, a single-group pre-post study design
      was adopted. Participants completed the outcome measures before and after the
      training program. There were six weekly sessions in total (about 1.5 hours, once
      weekly). RESULTS: Participants experienced a significant improvement in their
      emotional well-being after training. However, there were no significant changes
      in participants' cognitive function or health-related quality of life.
      CONCLUSION: Our results suggest that Playback Theatre as a community program has
      potential to improve the mental and emotional well-being of older people.

PMID- 29341377
TI  - Halogen Bonding in Solution: Anion Recognition, Templated Self-Assembly, and
      Organocatalysis.
AB  - The halogen bond is a supramolecular interaction between a Lewis-acidic region of
      a covalently bound halogen and a Lewis base. It has been studied widely in silico
      and experimentally in the solid state; however, solution-phase applications have
      attracted enormous interest in the last few years. This Minireview highlights
      selected recent developments in halogen bond interactions in solution, with a
      focus on the use of receptors based on halogen bonds in anion recognition and
      sensing, anion-templated self-assembly, as well as in organocatalysis.

PMID- 29341378
TI  - Halloysite Nanotubes: Green Nanomaterial for Functional Organic-Inorganic
      Nanohybrids.
AB  - The unique one-dimensional nanoporous structure and the reactive external and
      internal surfaces make halloysite nanotube (HNT) an interesting nanomaterial for
      various applications. HNT is a green nanomaterial because it is easily available
      from abundant deposits in nature and is biocompatible with low cytotoxicity.
      After a brief introduction on the structure of HNT, recent advances in surface
      modification of HNT and its functional organic-inorganic nanohybrids including
      hybrid nanocontainers, flame retardant nanocomposites, dye removal adsorbents,
      liquid marbles, and superamphiphobic coatings are introduced.

PMID- 29341379
TI  - Erector spinae plane block for inguinal hernia repair in preterm infants.
AB  - Neuro-axial anesthesia has been the preferred technique for inguinal hernia
      repair when attempting to avoid general anesthesia in neonates and preterm
      infants. We present a case where an erector spinae plane block was used
      successfully for this surgery. Hemodynamic stability, minimal anesthetic
      requirements, and excellent pain control were documented. This block promises to
      be a valuable and safe alternative for inguinal hernia repair, accompanying the
      path of neuroprotective anesthesia.

PMID- 29341380
TI  - Tuning the Adsorption Energy of Methanol Molecules Along Ni-N-Doped Carbon Phase
      Boundaries by the Mott-Schottky Effect for Gas-Phase Methanol Dehydrogenation.
AB  - Engineering the adsorption of molecules on active sites is an integral and
      challenging part for the design of highly efficient transition-metal-based
      catalysts for methanol dehydrogenation. A Mott-Schottky catalyst composed of Ni
      nanoparticles and tailorable nitrogen-doped carbon-foam (Ni/NCF) and thus tunable
      adsorption energy is presented for highly efficient and selective dehydrogenation
      of gas-phase methanol to hydrogen and CO even under relatively high weight hourly
      space velocities (WHSV). Both theoretical and experimental results reveal the key
      role of the rectifying contact at the Ni/NCF boundaries in tailoring the electron
      density of Ni species and enhancing the absorption energies of methanol
      molecules, which leads to a remarkably high turnover frequency (TOF) value (356
      mol methanol mol-1  Ni h-1 at 350  degrees C), outpacing previously reported
      bench-marked transition-metal catalysts 10-fold.

PMID- 29341381
TI  - Effect of ethanol on the antimicrobial properties of chlorhexidine over oral
      biofilm.
AB  - The aim of this study was to evaluate the effect of 95% ethanol irrigation, with
      5 or 10 min of action, on the antibacterial properties of 2% chlorhexidine (CHX),
      on oral biofilm, evaluated with confocal laser scanning microscopy (CLSM). Oral
      biofilm development was induced in 80 sterilized bovine dentin blocks,
      distributed in two groups (5 or 10 min) and 4 subgroups, according to time and
      the solution used: Saline (SALINE5, SALINE10); Saline followed by CHX
      (SALINE/CHX5, SALINE/CHX10); Ethanol (ETHANOL5, ETHANOL10), Ethanol followed by
      CHX (ETHANOL/CHX5, ETHANOL/CHX10). The surface of the block was dyed with
      Live/Dead(r) BacLight. Images from different areas were analyzed by BioImage L
      program. The total biovolum (um3), biovolum of live cells (green), percentage of
      live cells of the thickness of the biofilm visualized in CLSM and on surface
      biofilm were evaluated. Total biovolum and biovolum of living cells showed
      similar results among the different groups (p > .05). The percentage of living
      cells in total thickness of the biofilm also was similar among the groups (p >
      .05), except ETHANOL5, SALINE/CHX10, ETHANOL10, and ETHANOL/CHX10 that showed
      lower percentage than SALINE5 (p < .05). The ETHANOL10 and ETHANOL/CHX10 also
      showed lower percentage of living cells than ETHANOL/CHX5 and SALINE10 (p < .05).
      In relation to biofilm surface, SALINE/CHX5, SALINE/CHX10, ETHANOL5, ETHANOL10,
      ETHANOL/CHX5, and ETHANOL/CHX10 showed a lower percentage of living cells
      percentage than SALINE5 and SALINE10 groups (p < .05). Therefore, ethanol has no
      effect on antimicrobial properties of 2% chlorhexidine, prior when used as
      endodontic irrigating solution.

PMID- 29341382
TI  - Synthesis, Crystal Analysis, and Optoelectronic Properties of Diazole
      Functionalized Acenes and Azaacenes.
AB  - Doping heteroatoms into the skeletons of parent acenes can provide more
      opportunities to construct novel thermally and photostable organic pi-conjugated
      semiconductors. Herein, a family of diazole-decorated acenes (APyS and APySe) and
      azaacenes (PyP, PyTh, PyPy, PyPh, and PyAP) have been successfully synthesized
      through the classical reactions. Single-crystal X-ray analyses showed that these
      as-formed diazole-modified derivatives adopted a twisted topology configuration,
      whereas the azaacenes display reclining-chair architectures, besides a twisted
      structure. All these compounds displayed yellow or red light in solution.
      Moreover, their electrochemical behaviors were also examined. We also found that
      the azaacenes exhibited a positive spectroscopic response to acid.

PMID- 29341383
TI  - CO2 -Triggered Switchable Hydrophilicity of a Heterogeneous Conjugated Polymer
      Photocatalyst for Enhanced Catalytic Activity in Water.
AB  - Water compatibility for heterogeneous photocatalysts has been pursued for energy
      and environmental applications. However, there exists a trade-off between
      hydrophilicity and recyclability of the photocatalyst. Herein, we report a
      conjugated polymer photocatalyst with tertiary amine terminals that reversibly
      binds CO2 in water, thereby generating switchable hydrophilicity. The CO2 
      assisted hydrophilicity boosted the photocatalytic efficiency in aqueous medium
      with minimum dosage. When CO2 was desorbed, the photocatalyst could be simply
      regenerated from reaction media, facilitating the repeated use of photocatalyst.
      Hydrophilicity/hydrophobicity control of the polymer photocatalyst was
      successfully showcased through a variety of organic photoredox reactions under
      visible-light irradiation in water.

PMID- 29341384
TI  - Influence of spore and carrier material surface hydrophobicity on decontamination
      efficacy with condensing hydrogen peroxide vapour.
AB  - AIMS: To investigate the influence of surface hydrophobicity of carrier material
      (CM) and bacterial spores of Bacillus subtilis SA 22 and Bacillus atrophaeus (DSM
      675) on spore inactivation with condensing hydrogen peroxide (H2 O2 ) gas.
      METHODS AND RESULTS: Surface hydrophobicity of bacterial spores and CM was
      determined by means of contact angle measurement. Spores of B. subtilis showed
      water contact angles of 90 degrees , spores of B. atrophaeus showed water contact
      angles of 42 degrees . Above that, a resistance test against liquid H2 O2 at room
      temperature was conducted with resulting DH2O2 values of 101 s (B. subtilis) and
      906 s (B. atrophaeus). The spores were deposited on CMs of different wettability
      (water contact angles of 115-30 degrees ). The spores were applied either
      individually or as an 1 : 1 mixture of both spore species. Exposure of biological
      indicators (BI) with 5200 ppm of gaseous H2 O2 at 70 degrees C treatment
      temperature for defined times up to 10 s led to inactivation kinetics. Surfaces
      with high hydrophobicity showed faster spore inactivation than surfaces with
      lower hydrophobicity for single-spore species. Regarding the mixed BI, better
      survival of hydrophobic spores was expected. However, this effect can only be
      seen as a slight trend and is not significant after 10 s. CONCLUSIONS: Surface
      hydrophobicity of CMs does influence the decontamination with gaseous, condensing
      H2 O2 . However, surface hydrophobicity of spores in a mixed population does only
      have a small influence on inactivation results. SIGNIFICANCE AND IMPACT OF THE
      STUDY: The intensity of spore inactivation depends more on other factors than on
      the wettability of the bacterial spores. However, hydrophobic surfaces lead to
      faster inactivation effects and should thus be preferred for aseptic packaging
      technology.

PMID- 29341385
TI  - Biological and behavioral correlates of body weight status among rural Northeast
      Brazilian schoolchildren.
AB  - OBJECTIVES: The increase in the prevalence of overweight/obesity in youth is a
      public health problem worldwide; however, few studies have investigated its
      prevalence and correlates in children from the Brazilian Northeast region rural
      zone. The purpose of this study was (1) to estimate the prevalence of children's
      weight status according to sex, age, and birth weight categories; and (2) to
      investigate the links between biological and behavioral factors and weight
      categories. METHODS: The sample comprises 501 children (248 girls), aged 7-10
      years, classified as low weight, normal weight, overweight, and obese using body
      mass index cut-points. Predicted variables included birth weight, percentage of
      body fat (%BF), fat free mass (FFM), physical fitness, and gross motor
      coordination. RESULTS: Data showed differences among weight groups for the
      predictor variables. Results of the logistic regression revealed that sex, age,
      %BF, FFM, physical fitness, and motor coordination seem to be relevant predictors
      of children's weight status, while no significant effect was observed for birth
      weight. CONCLUSION: Children with lower physical fitness levels as well as those
      with lower motor coordination quotient are more likely to be overweight and/or
      obese. No significant relationship was observed between birth weight and weight
      status in childhood. Strategies to reduce childhood obesity should consider
      biological, behavioral, and also environmental predictors.

PMID- 29341386
TI  - At the core of reasoning: Dissociating deductive and non-deductive load.
AB  - In recent years, neuroimaging methods have been used to investigate how the human
      mind carries out deductive reasoning. According to some, the neural substrate of
      language is integral to deductive reasoning. According to others, deductive
      reasoning is supported by a language-independent distributed network including
      left frontopolar and frontomedial cortices. However, it has been suggested that
      activity in these frontal regions might instead reflect non-deductive factors
      such as working memory load and general cognitive difficulty. To address this
      issue, 20 healthy volunteers participated in an fMRI experiment in which they
      evaluated matched simple and complex deductive and non-deductive arguments in a 2
      * 2 design. The contrast of complex versus simple deductive trials resulted in a
      pattern of activation closely matching previous work, including frontopolar and
      frontomedial "core" areas of deduction as well as other "cognitive support" areas
      in frontoparietal cortices. Conversely, the contrast of complex and simple non
      deductive trials resulted in a pattern of activation that does not include any of
      the aforementioned "core" areas. Direct comparison of the load effect across
      deductive and non-deductive trials further supports the view that activity in the
      regions previously interpreted as "core" to deductive reasoning cannot merely
      reflect non-deductive load, but instead might reflect processes specific to the
      deductive calculus. Finally, consistent with previous reports, the classical
      language areas in left inferior frontal gyrus and posterior temporal cortex do
      not appear to participate in deductive inference beyond their role in encoding
      stimuli presented in linguistic format.

PMID- 29341387
TI  - Health service utilisation amongst urban Aboriginal and Torres Strait Islander
      children aged younger than 5 years registered with a primary health-care service
      in South-East Queensland.
AB  - AIM: The majority of Australia's Aboriginal and/or Torres Strait Islander
      children live in urban areas; however, little is known about their health service
      use. We aimed to describe health service utilisation amongst a cohort of urban
      Aboriginal and/or Torres Strait Islander children aged <5 years. METHODS: We
      analysed health service utilisation data collected in an ongoing prospective
      cohort study of children aged <5 years registered with an Aboriginal-owned and
      operated primary health-care service. Enrolled children were followed monthly for
      12 months, with data on health service utilisation collected at baseline and at
      each monthly follow-up. Health service utilisation rates, overall and by service
      provider and reason for presentation, were calculated and reported as incidence
      rates per 100 child-months with the corresponding 95% confidence intervals (CIs).
      RESULTS: Between February 2013 and November 2015, 180 children were enrolled, and
      1541 child-months of observation were available for analysis. The overall
      incidence of health service utilisation was 52.5 per 100 child-months (95% CI
      48.7-56.5); 81% of encounters were with general practitioners. Presentation rates
      were the highest for acute respiratory illnesses (30.7/100 child-months, 95% CI
      27.8-33.9). CONCLUSIONS: In this community, acute respiratory illnesses are
      predominant causes of health service utilisation in young children. The health
      care utilisation profile of these children presents important opportunities for
      health promotion and intervention.

PMID- 29341388
TI  - Venous anastomosis by piggyback technique to avoid twisting of the pediatric en
      bloc kidney grafts.
AB  - This is the first report of using piggyback technique for the venous anastomosis
      in two pediatric recipients of small en bloc kidneys, which was found to be
      effective to avoid twisting of the grafts and vessels. The donors were aged 2 and
      3 years with a body weight of 17 and 20 kg. The recipient age was 14 and 16 years
      with a body weight of 42 and 54 kg. The implantation was done extraperitoneally
      in the right iliac fossa. The donor's inferior vena cava was anastomosed to the
      recipient's distal caval vein side-to-side using 6-0 polydioxanone running suture
      as the piggyback technique, initially dealing with the short vena cava graft in
      the first case. At the end of the operation, the kidneys were positioned allowing
      the lateral aspect of each renal unit to face anteriorly as "closing the book."
      The cold ischemia time was 895 and 820 minutes, respectively. No vascular
      complication was observed postoperatively. The patients were discharged on POD 16
      and POD 21 with an eGFR of 94 and 102 mL/min/1.73 m2, respectively. The graft
      function is stable during the 5- and 7-month follow-up.

PMID- 29341389
TI  - Detection of Escherichia coli in ready-to-eat fresh vegetables using broad-host
      range recombinant phages.
AB  - AIM: To construct a simple method to detect Escherichia coli in ready-to-eat
      fresh vegetables using broad-host-range recombinant phages. METHODS AND RESULTS:
      Firstly, a gene encoding cytochrome c peroxidase (CCP) chromogenic enzyme was
      inserted into genomes of wild-type phages IP008 and IP052 to produce recombinant
      phages IP008BK and IP052BK. They were then used in the production of the
      chromogenic enzyme (CCP) through infection into E. coli. The method was then
      examined in the colorimetric detection of E. coli K12 in broth, and its
      appearance was confirmed by a significant change in absorbance after a few
      minutes of the enzyme assay. Secondly, the protocol using the recombinant phages
      for the detection of E. coli in vegetables, that is, lettuce and mustard greens,
      was investigated. A low E. coli concentration at 4 CFU per g vegetable was
      detected within 16.5 h that is of a shorter duration than agar plate methods and
      in some commonly known phage-based methods. CONCLUSION: The existence of E. coli
      as a faecal contamination indicator in two types of ready-to-eat fresh
      vegetables, that is, lettuce and mustard greens, can be identified by the broad
      host-range recombinant phages. SIGNIFICANCE AND IMPACT OF STUDY: The method is
      simple and convenient since it enables the detection of E. coli without expensive
      apparatus. It is applicable to other types of food samples.

PMID- 29341391
TI  - Control of Protein Activity and Gene Expression by Cyclofen-OH Uncaging.
AB  - The use of light to control the expression of genes and the activity of proteins
      is a rapidly expanding field. Whereas many of these approaches use fusion between
      a light-activable protein and the protein of interest to control the activity of
      the latter, it is also possible to control the activity of a protein by uncaging
      a specific ligand. In that context, controlling the activation of a protein fused
      to the modified estrogen receptor (ERT) by uncaging its ligand cyclofen-OH has
      emerged as a generic and versatile method to control the activation of proteins
      quantitatively, quickly, and locally in a live organism. We present that approach
      and its uses in a variety of physiological contexts.

PMID- 29341392
TI  - Cannabis use is associated with reduced prevalence of progressive stages of
      alcoholic liver disease.
AB  - BACKGROUND: Abusive alcohol use has well-established health risks including
      causing liver disease (ALD) characterized by alcoholic steatosis (AS),
      steatohepatitis (AH), fibrosis, cirrhosis (AC) and hepatocellular carcinoma
      (HCC). Strikingly, a significant number of individuals who abuse alcohol also use
      Cannabis, which has seen increased legalization globally. While cannabis has
      demonstrated anti-inflammatory properties, its combined use with alcohol and the
      development of liver disease remain unclear. AIM: The aim of this study was to
      determine the effects of cannabis use on the incidence of liver disease in
      individuals who abuse alcohol. METHODS: We analysed the 2014 Healthcare Cost and
      Utilization Project-Nationwide Inpatient Sample (NIS) discharge records of
      patients 18 years and older, who had a past or current history of abusive alcohol
      use (n = 319 514). Using the International Classification of Disease, Ninth
      Edition codes, we studied the four distinct phases of progressive ALD with
      respect to three cannabis exposure groups: non-cannabis users (90.39%), non
      dependent cannabis users (8.26%) and dependent cannabis users (1.36%). We
      accounted for the complex survey sampling methodology and estimated the adjusted
      odds ratio (AOR) for developing AS, AH, AC and HCC with respect to cannabis use
      (SAS 9.4). RESULTS: Our study revealed that among alcohol users, individuals who
      additionally use cannabis (dependent and non-dependent cannabis use) showed
      significantly lower odds of developing AS, AH, AC and HCC (AOR: 0.55 [0.48-0.64],
      0.57 [0.53-0.61], 0.45 [0.43-0.48] and 0.62 [0.51-0.76]). Furthermore, dependent
      users had significantly lower odds than non-dependent users for developing liver
      disease. CONCLUSIONS: Our findings suggest that cannabis use is associated with a
      reduced incidence of liver disease in alcoholics.

PMID- 29341390
TI  - Building a new research framework for social evolution: intralocus caste
      antagonism.
AB  - The breeding and non-breeding 'castes' of eusocial insects provide a striking
      example of role-specific selection, where each caste maximises fitness through
      different morphological, behavioural and physiological trait values. Typically,
      queens are long-lived egg-layers, while workers are short-lived, largely sterile
      foragers. Remarkably, the two castes are nevertheless produced by the same
      genome. The existence of inter-caste genetic correlations is a neglected
      consequence of this shared genome, potentially hindering the evolution of caste
      dimorphism: alleles that increase the productivity of queens may decrease the
      productivity of workers and vice versa, such that each caste is prevented from
      reaching optimal trait values. A likely consequence of this 'intralocus caste
      antagonism' should be the maintenance of genetic variation for fitness and
      maladaptation within castes (termed 'caste load'), analogous to the result of
      intralocus sexual antagonism. The aim of this review is to create a research
      framework for understanding caste antagonism, drawing in part upon conceptual
      similarities with sexual antagonism. By reviewing both the social insect and
      sexual antagonism literature, we highlight the current empirical evidence for
      caste antagonism, discuss social systems of interest, how antagonism might be
      resolved, and challenges for future research. We also introduce the idea that
      sexual and caste antagonism could interact, creating a three-way antagonism over
      gene expression. This includes unpacking the implications of haplodiploidy for
      the outcome of this complex interaction.

PMID- 29341393
TI  - Prognostic and therapeutic factors influencing the clinical outcome of
      hepatoblastoma after liver transplantation: A single-institute experience.
AB  - LT has contributed to an elevation in cure rates for patients with unresectable
      HB; however, patients with recurrent HB after LT have poor prognosis. To analyze
      the prognostic and therapeutic factors that influence the clinical outcome of
      patients with HB receiving LT, we retrospectively analyzed 24 patients with HB
      who underwent LT between 1997 and 2015. The 5-year OS rate of all patients was
      69.6+/-9.7%. The 5-year OS rate of 11 patients receiving salvage LT for recurrent
      tumor after a primary resection was comparable to that of 13 patients receiving
      primary LT. Among 12 evaluable patients receiving primary LT, six of 10 patients
      with a decline of serum AFP >95% at LT are currently alive and in remission,
      whereas two patients with a decline of AFP <=95% experienced post-LT relapse.
      Among 9 evaluable patients receiving salvage LT, all three patients with any
      decline of AFP at LT are currently alive in remission, and three of six patients
      with no response to pre-LT salvage chemotherapy are also alive and in remission.
      Response to chemotherapy may be a reliable marker for prediction of post-LT
      relapse, even for patients receiving salvage LT.

PMID- 29341394
TI  - Hydrolysis by catalytic IgGs of microRNA specific for patients with
      schizophrenia.
AB  - Significant importance of autoimmune changes in the pathogenesis of schizophrenia
      (SCZ) is not established. Here, we present the first evidence that autoantibodies
      of 100% SCZ patients possess RNase activity: sCMP > poly(C) > poly(A) > yeast
      RNA. In addition, we have got an unexpected result: there was revealed site
      specific hydrolysis of four known SCZ specific microRNAs (miR-137, miR-9-5p, miR
      219-2-3p, and miR-219a-5p) playing an important role in the regulation of several
      genes functioning. Three major of cleavage sites are located in the microRNA
      loops or duplex parts directly articulated with the loops. RNase abzymes can
      contribute to decreasing of microRNAs effects on the functioning of numerous
      genes and the products of their transcription. Therefore, abzymes with RNase
      activity may be to some extent important for the development of schizophrenia.
      (c) 2018 IUBMB Life, 70(2):153-164, 2018.

PMID- 29341395
TI  - Health of Southern Tasmanian 4- to 6-year-old children in out-of-home care
      compared to peers.
AB  - AIM: To compare the health of 4- to 6-year-old children in out-of-home care
      (OOHC) in Southern Tasmania with their peers. METHODS: Demographic and health
      data collection and prospective health assessment of all 4- to 6-year olds in
      OOHC in Southern Tasmania on 30 August 2011 was undertaken. Data were compared to
      Tasmanian and/or Australian peers. RESULTS: A total of 109 of 129 children aged 4
      to 6 years were included in the study. Time in OOHC was on average 38 (range 0
      76) months. Premature birth (18%), low birthweight (20%) and congenital
      malformations (10%) were more common compared to peers. Antenatal exposure to
      illicit or abused substances (71%), alcohol (51%) and cigarettes (79%) were very
      high. Vertically acquired hepatitis C was diagnosed in 2% with 33% exposed.
      Immunisation completion was 78% compared to 92.9% of Tasmanian peers. Obesity
      (11% vs. 6% Tasmanian children), hearing impairment (7% vs. 1% Tasmanian
      children) and dental caries (61% vs. 45% Tasmanian children) were all higher than
      peers. Hospitalisation due to injury was more than twice that of Tasmanian peers
      (32.1 vs. 12.6 per 1000 per year). Developmental delay was 50% on screening.
      Emotional or behavioural difficulties were seen in 54%. CONCLUSIONS: Children in
      OOHC have high health needs. Comprehensive health assessments offer an
      opportunity to better identify and manage these needs. High hepatitis C exposure
      in utero was unexpected. This study highlights the need for comprehensive health
      screening assessments for all children in OOHC. OOHC clinic data can be helpful
      in planning broad interventions for children in OOHC.

PMID- 29341396
TI  - Pediatrics and donor-derived disease transmission: The US OPTN experience.
AB  - PDDTE are tracked by the OPTN Ad Hoc DTAC. Specific evaluation of potential
      transmissions from pediatric deceased donors or the impact of donor-derived
      disease transmissions to pediatric organ recipients has not been previously
      undertaken. PDDTE reported to the DTAC between 2008 and 2013 were reviewed,
      characterized as proven, probable, possible, IWDT, unlikely, or excluded for both
      the whole event and each individual recipient. Pediatric donors and recipients
      were defined as being 0-17 years of age. Analysis was undertaken to characterize
      potential disease transmission from pediatric donors to adult or pediatric
      recipients and also to evaluate potential transmission from all donors to
      pediatric recipients. P/P cases were further analyzed. A total of 5238 pediatric
      deceased US donors accounted for 17 456 organ transplants during the study
      period; 103 PDDTE reports arose from these donors (2.0%). PDDTE were
      characterized as P/P (15%), possible (13%), IWDT (9%), unlikely, and excluded
      (63%). Disease was transmitted to 22 of 54 potentially exposed (adult and
      pediatric) recipients with six attributable deaths. An infectious pathogen
      accounted for 13/15 of the P/P PDDTE associated with pediatric donors, affecting
      19 of 50 potentially exposed recipients and resulting in five deaths. Four
      separate viral pathogens from six donors accounted for P/P transmissions to 11
      recipients with the unanticipated transmission of CMV most common. No pediatric
      donor transmitted HIV, HBV, or HCV. Bacteria, fungi, and parasites accounted for
      three (all staphylococci), three (Zygomycetes and Histoplasma), and two (both
      Toxoplasma) P/P transmissions from seven donors, respectively. From the recipient
      side, 11/11,188 pediatric recipient deceased and living donor transplants during
      the study period were associated with a P/P PDDTE (<0.1%) with infectious
      pathogens accounting for 9/11 P/P events. Infections were split among pathogen
      categories (bacteria 2, viruses 3, parasites 3, and fungi 1). Reporting rates of
      PDDTE involving pediatric donors were very low and similar to rates from all
      donors, with resulting P/P transmissions occurring in only 0.1% of exposed
      recipients, but transmissions were associated with six deaths. Rates of P/P
      transmission to pediatric recipients from any donor (<0.1%) were also very low
      and similar to that of all recipients. Additional studies are needed to compare
      the pattern and outcome of donor-derived disease transmission from and to
      pediatric and adult donor and recipients.

PMID- 29341397
TI  - Bi-allelic mutations of CCDC88C are a rare cause of severe congenital
      hydrocephalus.
AB  - Congenital or infantile hydrocephalus is caused by genetic and non-genetic
      factors and is highly heterogeneous in etiology. In recent studies, a limited
      number of genetic causes of hydrocephalus have been identified. To date,
      recessive mutations in the CCDC88C gene have been identified as a cause of non
      syndromic congenital hydrocephalus in three reported families. Here, we report
      the fourth known family with two affected individuals with congenital
      hydrocephalus due to a homozygous mutation in the CCDC88C gene identified by
      whole exome sequencing. Our two newly described children, as well as the
      previously published ones, all shared several features including severe infantile
      onset hydrocephalus, mild to severe intellectual delay, varying degrees of motor
      delay, and infantile onset seizures. All identified homozygous mutations in
      CCDC88C abolish the PDZ binding site necessary for proper CCDC88C protein
      function in the Wnt signaling pathway. Our report further establishes CCDC88C as
      one of the few known recessive causes of severe prenatal-onset hydrocephalus.
      Recognition of this syndrome has important diagnostic and genetic implications
      for families identified in the future.

PMID- 29341398
TI  - What are the outcomes of declining a public health service increased risk liver
      donor for patients on the liver transplant waiting list?
AB  - The tragedy of the national opioid epidemic has resulted in a significant
      increase in the number of opioid-related deaths and accordingly an increase in
      the number of potential donors designated Public Health Service (PHS) increased
      risk. Previous studies have demonstrated reluctance to use these PHS organs, and
      as a result, higher discard rates for these organs have been observed. All
      patients listed for liver transplantation in the United States from January 2005
      to December 2016 were investigated. Patients on the waiting list were divided
      into 2 groups: those in which a PHS liver was used for transplantation (accepted
      PHS group) and those in which a PHS liver was declined and transplanted into a
      recipient lower on the match run (declined PHS group). Intention-to-treat patient
      survival from the time of PHS offer was significantly higher in the accepted PHS
      compared with the declined PHS group (P < 0.001). On Cox multivariate regression,
      declining a PHS donor liver was associated with a hazard ratio of 2.36 (95%
      confidence interval, 2.23-2.49; P < 0.001). For patients in which a PHS organ
      offer was declined, 11.6% died or were delisted for being too sick within the
      subsequent year. Donor liver allografts implanted in the accepted PHS group were
      of a lower donor risk index (1.28 versus 1.44) compared with the non-PHS organs
      that patients in the declined PHS group ultimately received if they underwent
      transplantation. In conclusion, there is a significantly higher survival for
      patients in which a PHS liver is accepted and used compared with those patients
      in which a PHS organ is declined. These data will help inform decisions about
      whether or not to accept a PHS donor liver for both patients and transplant
      professionals. Liver Transplantation 24 497-504 2018 AASLD.

PMID- 29341399
TI  - Activation of the Hog1 MAPK by the Ssk2/Ssk22 MAP3Ks, in the absence of the
      osmosensors, is not sufficient to trigger osmostress adaptation in Saccharomyces
      cerevisiae.
AB  - Yeast cells respond to hyperosmotic stress by activating the high-osmolarity
      glycerol (HOG) pathway, which consists of two branches, Hkr1/Msb2-Sho1 and Sln1,
      which trigger phosphorylation and nuclear internalization of the Hog1 mitogen
      activated protein kinase. In the nucleus, Hog1 regulates gene transcription and
      cell cycle progression, which allows the cell to respond and adapt to
      hyperosmotic conditions. This study demonstrates that the uncoupling of the known
      sensors of both branches of the pathway at the level of Ssk1 and Ste11 impairs
      cell growth in hyperosmotic medium. However, under these conditions, Hog1 was
      still phosphorylated and internalized into the nucleus, suggesting the existence
      of an alternative Hog1 activation mechanism. In the ssk1ste11 mutant,
      phosphorylated Hog1 failed to associate with chromatin and to activate
      transcription of canonical hyperosmolarity-responsive genes. Accordingly, Hog1
      also failed to induce glycerol production at the levels of a wild-type strain.
      Inactivation of the Ptp2 phosphatase moderately rescued growth impairment of the
      ssk1ste11 mutant under hyperosmotic conditions, indicating that downregulation of
      the HOG pathway only partially explains the phenotypes displayed by the ssk1ste11
      mutant. Cell cycle defects were also observed in response to stress when Hog1 was
      phosphorylated in the ssk1ste11 mutant. Taken together, these observations
      indicate that Hog1 phosphorylation by noncanonical upstream mechanisms is not
      sufficient to trigger a protective response to hyperosmotic stress.

PMID- 29341400
TI  - Are trans diagnostic models of eating disorders fit for purpose? A consideration
      of the evidence for food addiction.
AB  - Explanatory models for eating disorders have changed over time to account for
      changing clinical presentations. The transdiagnostic model evolved from the
      maintenance model, which provided the framework for cognitive behavioural therapy
      for bulimia nervosa. However, for many individuals (especially those at the
      extreme ends of the weight spectrum), this account does not fully fit. New
      evidence generated from research framed within the food addiction hypothesis is
      synthesized here into a model that can explain recurrent binge eating behaviour.
      New interventions that target core maintenance elements identified within the
      model may be useful additions to a complex model of treatment for eating
      disorders.

PMID- 29341401
TI  - The prediction probabilities for emergence from sevoflurane anesthesia in
      children: A comparison of the perfusion index and the bispectral index.
AB  - BACKGROUND: Predicting recovery of consciousness is one of the most essential
      functions of anesthesia depth monitors in anesthesia practice. Perfusion index
      and bispectral index are 2 indicators of the anesthesia depth monitoring with
      different working principles. The progression of the anesthesia emergence stages
      reflected by those monitors has not been well understood, especially in pediatric
      patients. The goals of this study were to compare the prediction probabilities of
      perfusion index and bispectral index in predicting awakening and in
      differentiating the different levels of arousal during emergence after
      sevoflurane anesthesia in children undergoing open inguinal hernia repairs.
      METHODS: Forty-five patients, aged 1 to 5 years, ASA Status I or II and scheduled
      for elective open inguinal hernia repairs under general anesthesia were enrolled.
      The perfusion index and bispectral index were monitored simultaneously during
      anesthesia recovery. The University of Michigan Sedation Scale was applied to
      evaluate the clinical arousal levels during emergence. The prediction probability
      was used to assess the performance of perfusion index and bispectral index in
      predicting awakening and distinguishing different levels of arousal corresponding
      to the University of Michigan Sedation Scale during recovery. RESULTS: The
      prediction probability of perfusion index (PkPI-Awakening  = .81, 95% CI 0.73
      0.89) in differentiating full consciousness from unconsciousness during recovery
      was comparable to that of bispectral index (PkBIS- Awakening  = .86, 95% CI 0.79
      0.92) (P = .47). The prediction probability for perfusion index (PkPI-UMSS  =
      .61, 95% CI 0.55-0.73) and bispectral index (PkBIS-UMSS  = .64, 95% CI 0.53-0.69)
      had similar performance in distinguishing different University of Michigan
      Sedation Scale levels. CONCLUSION: Both the perfusion index and bispectral index
      performed comparably well in predicting awakening and different arousal levels
      when emerging from sevoflurane anesthesia in children.

PMID- 29341403
TI  - Robotic low anterior resection of rectal cancer with partial resection of urinary
      bladder and reconstruction - a video vignette.

PMID- 29341402
TI  - Isotope Substitution of Promiscuous Alcohol Dehydrogenase Reveals the Origin of
      Substrate Preference in the Transition State.
AB  - The origin of substrate preference in promiscuous enzymes was investigated by
      enzyme isotope labelling of the alcohol dehydrogenase from Geobacillus
      stearothermophilus (BsADH). At physiological temperature, protein dynamic
      coupling to the reaction coordinate was insignificant. However, the extent of
      dynamic coupling was highly substrate-dependent at lower temperatures. For benzyl
      alcohol, an enzyme isotope effect larger than unity was observed, whereas the
      enzyme isotope effect was close to unity for isopropanol. Frequency motion
      analysis on the transition states revealed that residues surrounding the active
      site undergo substantial displacement during catalysis for sterically bulky
      alcohols. BsADH prefers smaller substrates, which cause less protein friction
      along the reaction coordinate and reduced frequencies of dynamic recrossing. This
      hypothesis allows a prediction of the trend of enzyme isotope effects for a wide
      variety of substrates.

PMID- 29341404
TI  - Intra- and inter-subject variability for increases in serum ketone bodies in
      patients with type 2 diabetes treated with the sodium glucose co-transporter 2
      inhibitor canagliflozin.
AB  - Sodium glucose co-transporter 2 (SGLT2) inhibitors have been associated with
      increased serum ketone body levels in patients with type 2 diabetes mellitus
      (T2DM). In the present analysis we evaluated serum ketone body levels and
      variability in 1278 Japanese patients with T2DM treated with canagliflozin 100 or
      200 mg. Similar mean increases in ketone body concentrations of ~2-fold were seen
      with both canagliflozin doses. The median (interquartile range) percent change
      from baseline was 62% (0;180) for acetoacetate and 78% (2;236) for beta
      hydroxybutyrate. Approximately two-thirds of the variability in each ketone
      measure was attributed to intra-subject variability. Intra-subject variability
      was higher for serum ketones than other metabolites. Patients in the lowest
      response tertile exhibited no increase in ketones. Those in the highest response
      tertile tended to be male and have higher fasting plasma glucose levels, lower
      insulin levels, and longer T2DM duration at baseline. Moreover, changes in serum
      ketones were not fully explained by changes in plasma fatty acids, suggesting
      downstream effects of SGLT2 inhibition on hepatic metabolism that favour
      ketogenesis. In summary, increases in serum ketone bodies with canagliflozin were
      greater and more variable than changes in other metabolic measures in Japanese
      patients with T2DM.

PMID- 29341405
TI  - Haemophilia of the third age.

PMID- 29341406
TI  - Biosimilars and haemophilia.

PMID- 29341407
TI  - Corrigendum.

PMID- 29341408
TI  - IR Spectrum and Structure of Protonated Monosilanol: Dative Bonding between Water
      and the Silylium Ion.
AB  - We report the spectroscopic characterization of protonated monosilanol (SiH3 OH2+
      ) isolated in the gas phase, thus providing the first experimental determination
      of the structure and bonding of a member of the elusive silanol family. The SiH3
      OH2+ ion is generated in a silane/water plasma expansion, and its structure is
      derived from the IR photodissociation (IRPD) spectrum of its Ar cluster measured
      in a tandem mass spectrometer. The chemical bonding in SiH3 OH2+ is analyzed by
      density functional theory (DFT) calculations, providing detailed insight into the
      nature of the dative H3 Si+ -OH2 bond. Comparison with protonated methanol
      illustrates the differences in bonding between carbon and silicon, which are
      mainly related to their different electronegativity and the different energy of
      the vacant valence pz orbital of SiH3+ and CH3+ .

PMID- 29341409
TI  - Recognition of i-IF/TA as a component of the T cell-mediated rejection spectrum:
      Unselected population approach vs random case selection.

PMID- 29341410
TI  - Eating down the food chain: generalism is not an evolutionary dead end for
      herbivores.
AB  - The role of trophic specialisation in taxonomic diversification remains unclear.
      Plant specialists diversify faster than omnivores and animalivores, but at
      shorter macroevolutionary scales this pattern sometimes reverses. Here, we
      estimate the effect of diet diversification on speciation rates in noctilionoid
      bats, controlling for tree shape, rate heterogeneity and macroevolutionary
      regimes. We hypothesise that niche subdivision among herbivores positively
      relates to speciation rates, differing between macroevolutionary regimes. We
      found the rate at which new herbivorous lineages originate decreases as rates of
      diet evolution increase. Herbivores experience higher speciation rates, but
      generalist herbivores and predominantly herbivorous omnivores speciate faster
      than specialised herbivores, omnivores and animalivores. Generalised herbivory is
      not a dead end. We show that analysing ecological traits and diversification
      requires accounting for macroevolutionary regimes and within- and between-clade
      variation in evolutionary rates. Our approach overcomes the high false-positive
      rates of other methods and illuminates the roles of herbivory and specialisation
      in speciation.

PMID- 29341411
TI  - The effect of recanalization on long-term neurological outcome after cerebral
      venous thrombosis.
AB  - : Essentials The role of cerebral venous thrombosis (CVT) recanalization on
      neurologic outcome is still debated. We studied a large cohort of 508 CVT
      patients with 419 patient years of radiological follow-up. Recanalization rate is
      high during the first months after CVT and neurologic outcome is favorable. High
      recanalization grade of CVT independently predicts good neurological outcome.
      SUMMARY: Background Studies with limited sample size and with discordant results
      described the recanalization time-course of cerebral venous thrombosis (CVT). The
      neurological outcome after a first episode of CVT is good, but the role of
      recanalization on neurological dependence is still debated. Objectives The aim of
      the study is to assess the recanalization rate after cerebral venous thrombosis
      (CVT) and its prognostic role in long-term neurological outcome. Patients/Methods
      In a retrospective observational multicenter cohort study, patients with an acute
      first episode of CVT with at least one available imaging test during follow-up
      were enrolled. Patency status of the vessels was categorized as complete, partial
      or not recanalized. Neurological outcome was defined using the modified Rankin
      scale (mRS) as good (mRS = 0-1) or poor (mRS = 2-6). Results Five-hundred and
      eight patients (median [IQR] age, 39 [28.5-49] years; 26% male) were included.
      Complete or partial recanalization was not differently represented in patients
      undergoing scans at different periods of time (from 28-day to 3 month-period up
      to a 1-3 year-period). mRS at the time of follow-up imaging was available in 483
      patients; 92.8% of them had a mRS of 0-1. CVT recanalization (odds ratio [OR],
      2.56; 95% confidence interval [CI], 1.59-4.13) was positively associated, whereas
      cancer (OR, 0.29; 95% CI, 0.09-0.88), and personal history of venous
      thromboembolism (VTE) (OR, 0.36; 95% CI, 0.14-0.92) were negatively associated as
      independent predictors of favorable (mRS = 0-1) outcome at follow-up. Conclusions
      Most patients with a first CVT had complete or partial recanalization at follow
      up. Recanalization was independently associated with a favorable neurological
      outcome.

PMID- 29341412
TI  - Three-dimensional neuromelanin-sensitive magnetic resonance imaging of the
      substantia nigra in Parkinson's disease.
AB  - BACKGROUND AND PURPOSE: The aim was to investigate the diagnostic utility of
      signal intensity measurement of the substantia nigra pars compacta (SNc) using
      three-dimensional (3D) neuromelanin-sensitive magnetic resonance imaging (MRI),
      for discrimination of patients with Parkinson's disease (PD) from healthy
      controls. METHODS: T1-weighted neuromelanin-sensitive images of 16 patients with
      PD and 15 controls were quantitatively analyzed by placing circular 10 mm2
      regions of interest over the central and lateral parts of the bilateral SNc and
      anterior to the cerebral aqueduct at three levels of the midbrain. Signal
      intensities and contrast ratios (CRs) were calculated, after which significant
      differences, correlations, sensitivity and specificity were calculated. RESULTS:
      The CRs of the central and lateral SNc were significantly lower in patients with
      PD. Lateral CRs were lower than the central CRs in both groups and significantly
      correlated with duration of illness. CRs of central and lateral parts of the SNc
      also correlated with the Unified Parkinson's Disease Rating Scale III OFF state
      scores. Receiver operating characteristic analysis revealed lateral CRs to be
      more sensitive and central CRs to be more specific for the discrimination of
      patients with PD from controls. CONCLUSIONS: Contrast ratio analysis of the SNc
      using 3D neuromelanin-sensitive MRI may serve as a quick and accurate tool to
      discern between patients with PD and healthy controls.

PMID- 29341413
TI  - Effects of health insurance coverage on risky behaviors.
AB  - Prior to implementation of the Patient Protection and Affordable Care Act,
      dependent health insurance coverage was typically available only for young adults
      under the age of 19. As of September 2010, the Affordable Care Act extended
      dependent health insurance coverage to include young adults up to the age of 26.
      I use the National Health Interview Survey for the sample period from 2011 to
      2013 to analyze the causal relationship between the expansion of dependent
      coverage and risky behaviors including smoking and drinking as well as preventive
      care. I employ a regression discontinuity design to estimate the causal effect of
      health insurance coverage and overcome the endogeneity problem between insurance
      status and risky behaviors. When young adults become 26 years old, they are 7 to
      10 percentage points more likely to lose health insurance than young adults under
      the age of 26. Although young adults over the age of 26 are generally aged out of
      insurance coverage, presence or absence of health insurance does not affect their
      smoking and drinking behaviors and their access to preventive care.

PMID- 29341414
TI  - Post-translational incorporation of 3,4-dihydroxyphenylalanine into the C
      terminus of alpha-tubulin in living cells.
AB  - The C-terminal tyrosine (Tyr) of the alpha-tubulin chain is subjected to post
      translational removal and readdition in a process termed the
      "detyrosination/tyrosination cycle". We showed in previous studies using soluble
      rat brain extracts that l-3,4-dihydroxyphenylalanine (l-Dopa) is incorporated
      into the same site as Tyr. We now demonstrate that l-Dopa incorporation into
      tubulin also occurs in living cells. We detected such incorporation by
      determining the "tyrosination state" of tubulin before and after incubation of
      cells in the presence of l-Dopa. The presence of a tubulin isospecies following l
      Dopa incubation that was not recognized by antibodies specific to Tyr- and deTyr
      tubulin was presumed to reflect formation of Dopa-tubulin. l-Dopa was identified
      by HPLC as the C-terminal compound bound to alpha-tubulin. l-Dopa incorporation
      into tubulin was observed in Neuro 2A cells and several other cell lines, and was
      not due to de novo protein biosynthesis. Dopa-tubulin had microtubule-forming
      capability similar to that of Tyr- and deTyr-tubulin. l-Dopa incorporation into
      tubulin did not notably alter cell viability, morphology, or proliferation rate.
      CAD cells (a neuron-like cell line derived from mouse brain) are easily cultured
      under differentiating and nondifferentiating conditions, and can be treated with
      l-Dopa. Treatment of CAD cells with l-Dopa and consequent increase in l-Dopa
      tubulin resulted in reduction of microtubule dynamics in neurite-like processes.

PMID- 29341415
TI  - Operational sex ratio predicts the opportunity and direction of sexual selection
      across animals.
AB  - The operational sex ratio (OSR) has long been assumed to be a key ecological
      factor determining the opportunity and direction of sexual selection. However,
      recent theoretical work has challenged this view, arguing that a biased OSR does
      not necessarily result in greater monopolisation of mates and therefore stronger
      sexual selection in the mate-limited sex. Hence, the role of the OSR for shaping
      animal mating systems remains a conundrum in sexual selection research. Here we
      took a meta-analytic approach to test whether OSR explains interspecific
      variation in sexual selection metrics across a broad range of animal taxa. Our
      results demonstrate that the OSR predicts the opportunity for sexual selection in
      males and the direction of sexual selection in terms of sex differences in both
      the opportunity for sexual selection and the Bateman gradient (i.e. the selection
      differential of mating success), as predicted by classic theory.

PMID- 29341416
TI  - Resveratrol Influences Pancreatic Islets by Opposing Effects on Electrical
      Activity and Insulin Release.
AB  - SCOPE: Resveratrol is suggested to improve glycemic control by activation of
      sirtuin 1 (SIRT1) and has already been tested clinically. Our investigation
      characterizes the targets of resveratrol in pancreatic beta cells and their
      contribution to short- and long-term effects on insulin secretion. METHODS AND
      RESULTS: Islets or beta cells are isolated from C57BL/6N mice. Electrophysiology
      is performed with microelectrode arrays and patch-clamp technique, insulin
      secretion and content are determined by radioimmunoassay, cAMP is measured by
      enzyme-linked immunosorbent assay, and cytosolic Ca2+ concentration by
      fluorescence methods. Resveratrol (25 MUmol L-1 ) elevates [Ca2+ ]c and
      potentiates glucose-stimulated insulin secretion. These effects are associated
      with increased intracellular cAMP and are sensitive to the SIRT1 blocker Ex-527.
      Inhibition of EPAC1 by CE3F4 also abolishes the stimulatory effect of
      resveratrol. The underlying mechanism does not involve membrane depolarization as
      resveratrol even reduces electrical activity despite blocking KATP channels.
      Importantly, after prolonged exposure to resveratrol (14 days), the beneficial
      influence of the polyphenol on insulin release is lost. CONCLUSION: Resveratrol
      addresses multiple targets in pancreatic islets. Potentiation of insulin
      secretion is mediated by SIRT1-dependent activation of cAMP/EPAC1. Considering
      resveratrol as therapeutic supplement for patients with type 2 diabetes mellitus,
      the inhibitory influence on electrical excitability attenuates positive effects.

PMID- 29341417
TI  - Synthesis and Characterization of Photoactivatable Doxycycline Analogues Bearing
      Two-Photon-Sensitive Photoremovable Groups Suitable for Light-Induced Gene
      Expression.
AB  - We report the synthesis and photolytic properties of caged 9-aminodoxycycline
      derivatives modified with 2-{4'-bis-[2-(2methoxyethoxy)ethyl]-4-nitrobiphenyl-3
      yl}prop-1-oxy (EANBP) and PEG7-ylated (7-diethylamino-2-oxo-2H-chromen-4
      yl)methyl (PEG7-DEACM) groups. 9-Aminodoxycycline is a tetracycline analogue
      capable of activating transcription through the inducible TetOn transgene
      expression system and can be regioselectively coupled to two-photon-sensitive
      photo-removable protecting groups by carbamoylation. The EANBP-based caged 9
      aminodoxycycline showed complex photochemical reactions but did release 10 % of 9
      aminodoxycycline. However, 9-(PEG7-DEACMamino)doxycycline exhibited excellent
      photolysis efficiency at 405 nm with quantitative release of 9-aminodoxycycline
      and a 0.21 uncaging quantum yield. Thanks to the good two-photon sensitivity of
      the DEACM chromophore, 9-aminodoxycycline release by two-photon photolysis is
      possible, with calculated action cross-sections of up to 4.0 GM at 740 nm.
      Therefore, 9-(PEG7-DEACMamino)doxycycline represents a very attractive tool for
      the development of a light-induced gene expression method in living cells.

PMID- 29341418
TI  - Hand-held, clinical dual mode ultrasound - photoacoustic imaging of rat urinary
      bladder and its applications.
AB  - Urinary bladder imaging is critical to diagnose urinary tract disorders, and
      bladder cancer. There is a great need for safe, non-invasive, and sensitive
      imaging technique which enables bladder imaging. Photoacoustic imaging is a
      rapidly growing imaging technique for various biological applications. It can be
      combined with clinical ultrasound imaging system for hand-held, dual modal
      ultrasound-photoacoustic real-time imaging. Structural (bladder wall) and
      functional (accretion of nanoparticles) bladder imaging is shown here with
      combined ultrasound and photoacoustic imaging in rats. Photoacoustic images of
      bladder wall is shown using black ink as the contrast agent. Chicken tissues were
      stacked on the abdomen of the animal to demonstrate the feasibility of
      photoacoustic imaging till a depth of 2 cm. Also, the feasibility of
      photoacoustic imaging for a common bladder disorder, vesicoureteral reflux is
      studied using urinary tract mimicking phantom. It is also shown that a clinical
      ultrasound system can be used for photoacoustic imaging of non-invasive clearance
      study of gold nanorods from circulation by monitoring the gradual accumulation of
      the gold nanorods in the bladder. The time taken for accumulation of nanorods in
      the bladder can be used as an indicator of the clearance rate of the nanoparticle
      circulation from the body.

PMID- 29341419
TI  - Fatty liver index predicts incident diabetes in a Japanese general population
      with and without impaired fasting glucose.
AB  - AIM: Fatty liver is associated with the development of diabetes. However, to our
      knowledge, no study has examined the relationship between the fatty liver index
      (FLI), calculated scores of hepatic steatosis, and the development of diabetes
      among individuals without impaired fasting glucose (IFG). We aimed to examine
      whether FLI predicts the development of diabetes in individuals with and without
      IFG in a Japanese general population. METHODS: We selected 1498 men and 2941
      women who participated in Specific Health Checkups in Japan. We divided all
      participants into six groups according to tertiles of FLI (low, moderate, and
      high) and the presence or absence of IFG, by sex. We calculated hazard ratios for
      incident diabetes for each group using a Cox proportional hazard model, adjusting
      for potential confounders. RESULTS: During a mean follow-up period of 3.0 years,
      176 cases of diabetes in men and 320 cases in women were identified. Compared
      with the low FLI group without IFG, the high FLI group without IFG was
      significantly associated with incident diabetes in both men (hazard ratio, 1.90;
      95% confidence interval, 1.08-3.36) and women (hazard ratio, 1.72; 95% confidence
      interval, 1.18-2.51). All IFG groups were significantly associated with incident
      diabetes regardless of FLI levels. CONCLUSIONS: Our results showed that FLI is
      associated with the development of diabetes regardless of sex and the presence or
      absence of IFG, and that it may be a useful predictor of future risk of incident
      diabetes even in individuals without IFG.

PMID- 29341420
TI  - Transgenic mice specifically expressing amphiregulin in white adipose tissue
      showed less adipose tissue mass.
AB  - To determine adipocytokines that play a regulatory role during obesity
      development, we explored the genes that encode growth factors and investigated
      the physiological functions for adipose tissue development. Here, we isolated
      amphiregulin (Areg) gene whose expression was significantly up-regulated in obese
      adipose tissues. Areg mRNA level was positively correlated with macrophage marker
      gene expression in adipose tissues in vivo. Unexpectedly, Areg transgenic mice
      showed less adipose tissue mass with increased mRNA expression levels of Tnf
      alpha and peroxisome proliferator-activated receptor gamma coactivator 1alpha
      (Pgc-1alpha) and delayed white adipose tissue development during the convalescent
      stage in a dextran sodium sulfate-induced colitis model. This study showed that
      Areg mRNA expression was significantly up-regulated in obese adipose tissues and
      over-expression of Areg in white adipose tissue caused less adipose tissue mass.

PMID- 29341421
TI  - A Stable Room-Temperature Luminescent Biphenylmethyl Radical.
AB  - There is only one family of room-temperature luminescent radicals, the
      triphenylmethyl radicals, to date. Herein, we synthesize a new stable room
      temperature luminescent radical, (N-carbazolyl)bis(2,4,6-tirchlorophenyl)methyl
      radical (CzBTM), which has improved properties compared to the triphenylmethyl
      radicals. X-ray crystallography, electron paramagnetic resonance spectroscopy,
      and magnetic susceptibility measurements confirmed the radical structure. CzBTM
      shows room-temperature deep-red to near-infrared emission in various solutions.
      Both thermal and photo stability were significantly enhanced by the replacement
      of trichlorobenzene by the carbazole moiety. The electroluminescence results of
      CzBTM verify its potential application to circumvent the problem of triplet
      harvesting in traditional fluorescent OLEDs. A new family of stable luminescent
      radicals based on CzBTM is anticipated.

PMID- 29341422
TI  - Synthesis and luminescence properties of cubic-shaped Ca1-x TiO3 :Eu3+ particles.
AB  - In this article Ca1-x TiO3 :xEu3+ single crystalline particles with a cubic
      morphology and average size of 248 to 815 nm were synthesized by a solvothermal
      method. The structural and optical properties of the Ca1-x TiO3 :xEu3+ cubes were
      investigated, the formation mechanism of the cubes were analyzed and discussed,
      and the influence of Eu doping content and cubic size on the photoluminescence
      were examined. The differences in the photoluminescence between Ca1-x TiO3 :xEu3+
      cubic crystals and nanoparticles was analyzed. It was found that an addition of a
      small amount of water can substantially reduce the size of the cubes. An obvious
      red emission band centered at 615 nm was observed under the excitation at 395 nm
      for the cubes. Our results demonstrate CaTiO3 cubes are good host materials for
      designing red phosphors.

PMID- 29341423
TI  - Variable immune deficiency related to deletion size in chromosome 22q11.2
      deletion syndrome.
AB  - The clinical features of 22q11.2 deletion syndrome include virtually every organ
      of the body. This review will focus on the immune system and the differences
      related to deletion breakpoints. A hypoplastic thymus was one of the first
      features described in this syndrome and low T cell counts, as a consequence of
      thymic hypoplasia, are the most commonly described immunologic feature. These are
      most prominently seen in early childhood and can be associated with increased
      persistence of viruses. Later in life, evidence of T cell exhaustion may be seen
      and secondary deficiencies of antibody function have been described. The
      relationship of the immunodeficiency to the deletion breakpoints has been
      understudied due to the infrequent analysis of people carrying smaller deletions.
      This manuscript will review the immune deficiency in 22q11.2 deletion syndrome
      and describe differences in the T cell counts related to the deletion
      breakpoints. Distal, non-TBX1 inclusive deletions, were found to be associated
      with better T cell counts. Another new finding is the relative preservation of T
      cell counts in those patients with a 22q11.2 duplication.

PMID- 29341424
TI  - Fetal ultrasonographic findings including cerebral hyperechogenicity in a patient
      with non-lethal form of Raine syndrome.
AB  - Raine syndrome is a rare osteosclerotic bone dysplasia characterized by
      craniofacial anomalies and intracranial calcification. Most patients with Raine
      syndrome are of Arab ancestry and die during the neonatal period. We herein
      report a Japanese patient with non-lethal Raine syndrome who presented with
      characteristic cerebral hyperechogenicity and a hypoplastic nose by fetal
      ultrasonography. She was admitted to the NICU due to pyriform aperture stenosis.
      Craniofacial abnormalities, intracranial calcification, osteosclerosis,
      chondrodysplasia punctata, and a mutation of FAM20C was identified. She was
      subsequently discharged without surgical intervention and is now 2 years old with
      mild neurodevelopmental delays. Images of cerebral hyperechogenicity by fetal
      ultrasonography in a non-lethal case were described herein for the first time.
      This patient represents a rare occurrence of a child with Raine syndrome born to
      Japanese parents and confirms that this syndrome is not always lethal. Even if
      Raine syndrome is suspected in a fetus due to cerebral hyperechogenicity and a
      hypoplastic nose, cerebral hyperechogenicity without pulmonary hypoplasia does
      not always predict lethality or severe neurodevelopmental delays. The information
      provided herein will be useful for prenatal counseling.

PMID- 29341425
TI  - Synthesis of novel Dy3+ activated Ba2 CaZn2 Si6 O17 phosphors for white light
      emitting diodes.
AB  - Dysprosium ion (Dy3+ ) activated Ba2 CaZn2 Si6 O17 phosphors were synthesized
      using high temperature solid-state reaction method. Powder X-ray diffraction
      (PXRD) analysis confirmed the phase formation of the as-prepared phosphors.
      Scanning electron microscopy (SEM) analysis disclosed an agglomeration of
      particles with an irregular morphology. Under 350 nm excitation, the emission
      spectrum of Dy3+ ions showed bands at 481 nm (blue), 577 nm (yellow) and 674 nm
      (red). The influence of the Dy3+ concentration on its emission intensity was
      investigated. The optimum concentration of Dy3+ ions in the Ba2 CaZn2 Si6 O17
      :Dy3+ phosphors were found to be x = 0.06. The critical energy transfer distance
      was calculated. The fluorescence lifetime was also determined for Ba2 CaZn2 Si6
      O17 :0.06Dy3+ . The Commission International deI'Eclairage (CIE) chromaticity
      coordinates of the phosphor were calculated to be x = 0.304, y = 0.382. The
      activation energy for the thermal quenching was calculated to be 0.168 eV. These
      results indicated that the Ba2 CaZn2 Si6 O17 :Dy3+ phosphor might be a potential
      candidate for near ultraviolet (NUV)-based white light-emitting diodes.

PMID- 29341426
TI  - Biomechanical, histological, and computed X-ray tomographic analyses of
      hydroxyapatite coated PEEK implants in an extended healing model in rabbit.
AB  - A nanosized hydroxyapatite (HA) modification on polyetheretherketone (PEEK) using
      a novel spin coating technique was investigated in a rabbit model. Spin coating
      technique creates a 20-40 nm thick layer of nanosized HA particles with similar
      shape, size, and crystallinity as human bone. Some implants were designed with a
      perforating hole in the apical region to mimic a fusion chamber of a spinal
      implant. The coating nano-structures were assessed using a scanning electron
      microscope. The in vivo response to HA-PEEK was compared to untreated PEEK with
      respect to removal torque, histomorphometry, and computed microtomography. The HA
      coated and pure PEEK implants were inserted in the tibia and femur bone according
      to simple randomization. The rabbits were sacrificed 20 weeks after implantation.
      Removal torque analysis showed significantly higher values for HA-PEEK.
      Qualitative histological evaluation revealed an intimate contact between PEEK and
      the bone at the threads and perforated hole. Histomorphometric assessment showed
      higher bone-implant and bone area values for HA-PEEK but without statistical
      significance. The effect of the HA coating showed most prominent effect in the
      removal torque which may be correlated to an alteration in the bone quality
      around the HA-PEEK implants. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res
      Part A: 106A: 1440-1447, 2018.

PMID- 29341427
TI  - LC/MS-based Intact IgG and Released Glycan Analysis for Bioprocessing
      Applications.
AB  - Robust plate based antibody glycan analysis platforms are urgently needed for
      biopharmaceutical development and manufacturing as well as for clinical biomarker
      research. A 96-well plate based workflow has been developed to analyze both
      intact IgG antibodies and released N-glycans using an Orbitrap Fusion Mass
      Spectrometer and an LC/MS method on the Waters UNIFI platform. Here, such a
      workflow including protein A purification, PNGaseF digestion, 2-AB labeling, and
      SPE clean-up is described. The measured IgG glycan profile is consistent with
      that obtained from non-plate based method and commercial kit and has the
      advantage of less hands-on time. Also the application of the workflow in cell
      culture monitoring and clonal selection work is demonstrated. Apart from checking
      the major glycan structure changes among clones, post translational modifications
      (PTMs) such as C-terminal lysine residue clipping and N-terminal pyroglutamic
      acid formation can also be deduced from the workflow.

PMID- 29341428
TI  - Epigenetic Silencing of TAP1 in Aldefluor+ Breast Cancer Stem Cells Contributes
      to Their Enhanced Immune Evasion.
AB  - Avoiding detection and destruction by immune cells is key for tumor initiation
      and progression. The important role of cancer stem cells (CSCs) in tumor
      initiation has been well established, yet their ability to evade immune detection
      and targeting is only partly understood. To investigate the ability of breast
      CSCs to evade immune detection, we identified a highly tumorigenic population in
      a spontaneous murine mammary tumor based on increased aldehyde dehydrogenase
      activity. We performed tumor growth studies in immunocompetent and
      immunocompromised mice. In immunocompetent mice, growth of the spontaneous
      mammary tumor was restricted; however, the Aldefluor+ population was expanded,
      suggesting inherent resistance mechanisms. Gene expression analysis of the sorted
      tumor cells revealed that the Aldefluor+ tumor cells has decreased expression of
      transporter associated with antigen processing (TAP) genes and co-stimulatory
      molecule CD80, which would decrease susceptibility to T cells. Similarly, the
      Aldefluor+ population of patient tumors and 4T1 murine mammary cells had
      decreased expression of TAP and co-stimulatory molecule genes. In contrast,
      breast CSCs identified by CD44+ CD24- do not have decreased expression of these
      genes, but do have increased expression of C-X-C chemokine receptor type 4.
      Decitabine treatment and bisulfite pyrosequencing suggests that DNA
      hypermethylation contributes to decreased TAP gene expression in Aldefluor+ CSCs.
      TAP1 knockdown resulted in increased tumor growth of 4T1 cells in immunocompetent
      mice. Together, this suggests immune evasion mechanisms in breast CSCs are marker
      specific and epigenetic silencing of TAP1 in Aldefluor+ breast CSCs contributes
      to their enhanced survival under immune pressure. Stem Cells 2018;36:641-654.

PMID- 29341430
TI  - Tuberculosis vaccines: Opportunities and challenges.
AB  - Tuberculosis (TB) is a serious disease around the world. Bacillus Calmette-Guerin
      (BCG) is the only TB vaccine licensed for use in human beings, and is effective
      in protecting infants and children against severe miliary and meningeal TB.
      However, BCG's protective efficacy is variable in adults. Novel TB vaccine
      candidates being developed include whole-cell vaccines (recombinant BCG (rBCG),
      attenuated Mycobacterium tuberculosis, killed M. tuberculosis or Mycobacterium
      vaccae), adjuvanted protein subunit vaccines, viral vector-delivered subunit
      vaccines, plasmid DNA vaccines, RNA-based vaccines etc. At least 12 novel TB
      vaccine candidates are now in clinical trials, including killed M. vaccae, rBCG
      DeltaureC::hly, adjuvanted fusion proteins M72 and H56 and viral vectored MVA85A.
      Unfortunately, in TB, there are no correlates of vaccine-induced protection,
      although cell-mediated immune responses such as interferon-gamma (IFN-gamma)
      production are widely used to assess vaccine's immunogenicity. Recent studies
      suggested that central memory T cells and local secreted IgA correlated with
      protection against TB disease. Clinical TB vaccine efficacy trials should invest
      in identifying correlates of protection, and evaluate new TB biomarkers emerging
      from human and animal studies. Accumulating new knowledge on M. tuberculosis
      antigens and immune profiles correlating with protection or disease risk will be
      of great help in designing next generation of TB vaccines.

PMID- 29341431
TI  - Risk of infantile hemangiomas in the offspring of women with autoimmune disease
      and the pathogenic implications of these lesions.
AB  - The purpose of this study was to analyze the risk of maternal autoimmune disease
      or associated treatments on infantile hemangiomas (IHs), a common benign vascular
      tumor in infants, and to better understand how maternal chronic inflammation may
      play a factor in the pathogenesis of these lesions. Eligible women from the
      United States and Canada who enrolled before 19 weeks' gestation and delivered at
      least one live born infant were recruited as part of the Organization of
      Teratology Information Specialists (OTIS) Autoimmune Disease in Pregnancy Project
      from 2004-2013. A total of 51/969 (5.3%) and 8/240 (3.3%) infants with IH were
      born to mothers with and without autoimmune disease, respectively (OR 1.61;
      95%CI, 0.75-.44). The presence of ulcerative colitis (UC) in the mother was
      significantly associated with IH in the child (OR 3.46; 95%CI, 1.29-9.26). The
      five largest IH occurred within the autoimmune disease cohort and to women taking
      a biologic medication. These results imply that UC may be a risk factor for IH
      development, and that chronic inflammation may influence the development of these
      lesions. This potential link between IH and autoimmune disease warrants further
      investigation.

PMID- 29341433
TI  - Corrigendum.

PMID- 29341432
TI  - Duck "beak atrophy and dwarfism syndrome" disease complex: Interplay of novel
      goose parvovirus-related virus and duck circovirus?
AB  - As a newly emerged infectious disease, duck "beak atrophy and dwarfism syndrome
      (BADS)" disease has caused huge economic losses to waterfowl industry in China
      since 2015. Novel goose parvovirus-related virus (NGPV) is believed the main
      pathogen of BADS disease; however, BADS is rarely reproduced by infecting ducks
      with NGPV alone. As avian circovirus infection causes clinical symptoms similar
      to BADS, duck circovirus (DuCV) is suspected the minor pathogen of BADS disease.
      In this study, an investigation was carried out to determine the coinfection of
      NGPV and DuCV in duck embryos and in ducks with BADS disease. According to our
      study, the coinfection of emerging NGPV and DuCV was prevalent in East China
      (Shandong, Jiangsu and Anhui province) and could be vertical transmitted,
      indicating their cooperative roles in duck BADS disease.

PMID- 29341429
TI  - Trans-acting translational regulatory RNA binding proteins.
AB  - The canonical molecular machinery required for global mRNA translation and its
      control has been well defined, with distinct sets of proteins involved in the
      processes of translation initiation, elongation and termination. Additionally,
      noncanonical, trans-acting regulatory RNA-binding proteins (RBPs) are necessary
      to provide mRNA-specific translation, and these interact with 5' and 3'
      untranslated regions and coding regions of mRNA to regulate ribosome recruitment
      and transit. Recently it has also been demonstrated that trans-acting ribosomal
      proteins direct the translation of specific mRNAs. Importantly, it has been shown
      that subsets of RBPs often work in concert, forming distinct regulatory complexes
      upon different cellular perturbation, creating an RBP combinatorial code, which
      through the translation of specific subsets of mRNAs, dictate cell fate. With the
      development of new methodologies, a plethora of novel RNA binding proteins have
      recently been identified, although the function of many of these proteins within
      mRNA translation is unknown. In this review we will discuss these methodologies
      and their shortcomings when applied to the study of translation, which need to be
      addressed to enable a better understanding of trans-acting translational
      regulatory proteins. Moreover, we discuss the protein domains that are
      responsible for RNA binding as well as the RNA motifs to which they bind, and the
      role of trans-acting ribosomal proteins in directing the translation of specific
      mRNAs. This article is categorized under: RNA Interactions with Proteins and
      Other Molecules > RNA-Protein Complexes Translation > Translation Regulation
      Translation > Translation Mechanisms.

PMID- 29341434
TI  - Recombinant collagen scaffolds as substrates for human neural stem/progenitor
      cells.
AB  - Adhesion to the microenvironment profoundly affects stem cell functions,
      including proliferation and differentiation, and understanding the interaction of
      stem cells with the microenvironment is important for controlling their behavior.
      In this study, we investigated the effects of the integrin binding epitopes
      GFOGER and IKVAV (natively present in collagen I and laminin, respectively) on
      human neural stem/progenitor cells (hNSPCs). To test the specificity of these
      epitopes, GFOGER or IKVAV were placed within the context of recombinant triple
      helical collagen III engineered to be devoid of native integrin binding sites.
      HNSPCs adhered to collagen that presented GFOGER as the sole integrin-binding
      site, but not to IKVAV-containing collagen. For the GFOGER-containing collagens,
      antibodies against the beta1 integrin subunit prevented cellular adhesion,
      antibodies against the alpha1 subunit reduced cell adhesion, and antibodies
      against alpha2 or alpha3 subunits had no significant effect. These results
      indicate that hNSPCs primarily interact with GFOGER through the alpha1beta1
      integrin heterodimer. These GFOGER-presenting collagen variants also supported
      differentiation of hNSPCs into neurons and astrocytes. Our findings show, for the
      first time, that hNSPCs can bind to the GFOGER sequence, and they provide
      motivation to develop hydrogels formed from recombinant collagen variants as a
      cell delivery scaffold. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part
      A: 106A: 1363-1372, 2018.

PMID- 29341435
TI  - Bifunctional Fluorescent Probe for Sequential Sensing of Thiols and Primary
      Aliphatic Amines in Distinct Fluorescence Channels.
AB  - Thiols and primary aliphatic amines (PAA) are ubiquitous and extremely important
      species in biological systems. They perform significant interplaying roles in
      complex biological events. A single fluorescent probe differentiating both thiols
      and PAA can contribute to understanding the intrinsic inter-relationship of
      thiols and PAA in biological processes. Herein, we rationally constructed the
      first fluorescent probe that can respond to thiols and PAA in different
      fluorescence channels. The probe exhibited a high selectivity and sensitivity to
      thiols and PAA. In addition, it displayed sequential sensing ability when the
      thiols and PAA coexisted. The application experiments indicated that the probe
      can be used for sensing thiols and PAA in human blood serum. Moreover, the
      fluorescence imaging of endogenous thiols and PAA as well as antihypertensive
      drugs captopril and amlodipine in living cells were successfully conducted.

PMID- 29341436
TI  - A novel near-infrared fluorescent probe for monitoring cyclooxygenase-2 in
      inflammation and tumor.
AB  - Targeting cyclooxygenase-2 (COX-2) for molecular imaging is an attractive
      approach applicable for its overexpression in inflammation and many malignancies.
      Herein, for monitoring COX-2, we synthesize a specific COX-2 probe celecoxib-MPA
      probe (CMP), based on celecoxib and a water-soluble near-infrared dye dye ICG-Der
      02 (MPA). Its high affinity for binding to COX-2 is verified by molecular
      docking, dynamics simulation and inhibition assay. At cellular level, CMP
      selectively accumulates in cytoplasm of COX-2-positive cells. in vivo assays,
      probe guided-imaging in inflamed or cancerous tissues confirms that CMP can bind
      to the locally endogenic COX-2 and exhibit intense fluorescence. Importantly, we
      further prove the targeting specificity of CMP as the fluorescence is
      significantly reduced by blocking COX-2 active site through preinjection with
      celecoxib. The results suggest that the probe CMP, with favorable hydrophilic
      property, good biocompatibility, long-term observation, excellent targeting
      ability and optical imaging capability, could serve as a promising probe for real
      time monitoring COX-2 in inflammation and tumor.

PMID- 29341437
TI  - Phenotypic heterogeneity of ZMPSTE24 deficiency.
AB  - A 4-year-old girl was referred to the Undiagnosed Diseases Network with a history
      of short stature, thin and translucent skin, macrocephaly, small hands, and
      camptodactyly. She had been diagnosed with possible Hallerman-Streiff syndrome.
      Her evaluation showed that she was mosaic for uniparental isodisomy of chromosome
      1, which harbored a pathogenic c.1077dupT variant in ZMPSTE24 which predicts
      p.(Leu362fsX18). ZMPSTE24 is a zinc metalloproteinase that is involved in
      processing farnesylated proteins and pathogenic ZMPSTE24 variants cause
      accumulation of abnormal farnesylated forms of prelamin A. This, in turn, causes
      a spectrum of disease severity which is based on enzyme activity. The current
      patient has an intermediate form, which is a genocopy of severe Progeria.

PMID- 29341440
TI  - Response to Hostetler.

PMID- 29341439
TI  - Therapeutic benefits of CD90-negative cardiac stromal cells in rats with a 30-day
      chronic infarct.
AB  - Cardiac stromal cells (CSCs) can be derived from explant cultures, and a subgroup
      of these cells is viewed as cardiac mesenchymal stem cells due to their
      expression of CD90. Here, we sought to determine the therapeutic potential of
      CD90-positive and CD90-negative CSCs in a rat model of chronic myocardial
      infarction. We obtain CD90-positive and CD90-negative fractions of CSCs from rat
      myocardial tissue explant cultures by magnetically activated cell sorting. In
      vitro, CD90-negative CSCs outperform CD90-positive CSCs in tube formation and
      cardiomyocyte functional assays. In rats with a 30-day infarct, injection of CD90
      negative CSCs augments cardiac function in the infarct in a way superior to that
      from CD90-positive CSCs and unsorted CSCs. Histological analysis revealed that
      CD90-negative CSCs increase vascularization in the infarct. Our results suggest
      that CD90-negative CSCs could be a development candidate as a new cell therapy
      product for chronic myocardial infarction.

PMID- 29341441
TI  - Organic Microcrystal Vibronic Lasers with Full-Spectrum Tunable Output beyond the
      Franck-Condon Principle.
AB  - The very broad emission bands of organic semiconductor materials are, in theory,
      suitable for achieving versatile solid-state lasers; however, most of organic
      materials only lase at short wavelength corresponding to the 0-1 transition
      governed by the Franck-Condon (FC) principle. A strategy is developed to overcome
      the limit of FC principle for tailoring the output of microlasers over a wide
      range based on the controlled vibronic emission of organic materials at
      microcrystal state. For the first time, the output wavelength of organic lasers
      is tailored across all vibronic (0-1, 0-2, 0-3, and even 0-4) bands spanning the
      entire emission spectrum.

PMID- 29341438
TI  - Natural antisense transcripts in diseases: From modes of action to targeted
      therapies.
AB  - Antisense transcription is a widespread phenomenon in mammalian genomes, leading
      to production of RNAs molecules referred to as natural antisense transcripts
      (NATs). NATs apply diverse transcriptional and post-transcriptional regulatory
      mechanisms to carry out a wide variety of biological roles that are important for
      the normal functioning of living cells, but their dysfunctions can be associated
      with human diseases. In this review, we attempt to provide a molecular basis for
      the involvement of NATs in the etiology of human disorders such as cancers and
      neurodegenerative and cardiovascular diseases. We also discuss the pros and cons
      of oligonucleotide-based therapies targeted against NATs, and we comment on state
      of-the-art progress in this promising area of clinical research. WIREs RNA 2018,
      9:e1461. doi: 10.1002/wrna.1461 This article is categorized under: RNA in Disease
      and Development > RNA in Disease Regulatory RNAs/RNAi/Riboswitches > Regulatory
      RNAs RNA Interactions with Proteins and Other Molecules > Small Molecule-RNA
      Interactions.

PMID- 29341442
TI  - Motivating influences and ability-based outcomes of dental hygiene baccalaureate
      education in Canada.
AB  - BACKGROUND: There is a scarcity of studies on Canadian baccalaureate dental
      hygienists. As discussions about baccalaureate education for dental hygiene
      continue on a national level, examining outcomes of earning a dental hygiene
      degree is paramount. OBJECTIVE: To investigate the motivating reasons and ability
      based outcomes of earning a Bachelor of Dental Science in Dental Hygiene (BDSc)
      degree from the University of British Columbia (UBC), Canada. METHODS: UBC dental
      hygiene entry-to-practice (ETP) and degree-completion (DC) graduates (n = 116;
      32%) from 1994 to 2016 participated in an online mixed-methods survey. Survey
      questions explored motivating reasons for pursuing dental hygiene degree
      education and abilities gained during their degree. RESULTS: Primary reasons for
      pursuing a degree were personal satisfaction (82%), increasing knowledge base
      (82%), increasing employment opportunities (78%), status/recognition of a degree
      (76%), accessing graduate education (68%) and improving critical thinking
      abilities (61%). For DC graduates, abilities strengthened included enhanced
      skills for appraising research (92%), enhanced critical thinking and problem
      solving skills (90%), enhanced skills for retrieving scientific information (88%)
      and increased value for lifelong learning (84%). Enhanced abilities positively
      influenced client care in the areas of evidence-based decision-making,
      communicating information to clients, and collaborating with other professionals.
      Overall, 93% of respondents believe a baccalaureate degree should be the ETP
      credential for dental hygiene because it enhances critical thinking and better
      prepares graduates for diverse roles in society with more complex populations.
      CONCLUSION: The results highlight the impact of baccalaureate education on dental
      hygiene practice in Canada.

PMID- 29341443
TI  - Stachyose Improves Inflammation through Modulating Gut Microbiota of High-Fat
      Diet/Streptozotocin-Induced Type 2 Diabetes in Rats.
AB  - SCOPE: The present study is undertaken to assess the effects of stachyose (STS)
      on type 2 diabetes in rats and changes in the gut microbiota compared to
      metformin (MET). METHODS AND RESULTS: The type 2 diabetic model is successfully
      established via a high-fat diet /streptozotocin in Wistar rats, and STS or MET is
      administered for 4 weeks. Blood is collected to analyze biochemical parameters,
      pancreas for mRNA expression of related gene, and contents of colon for gut
      microbiota. STS or MET decreases serum LPS, mRNA expression of IL-6, and tumor
      necrosis factor-alpha (TNF-alpha). In addition, STS and MET show a similar
      shifting of the structure of the gut microbiota and a selective enrichment of key
      species. At the genus level, STS shows selective enrichment of
      Phascolarctobacterium, Bilophila, Oscillospira, Turicibacter, and SMB5, but MET
      demonstrates a selective effect on Sutterella, Prevotella, 02d06, and rc4. The
      correlation analysis indicates that STS and MET decrease IL-6 and TNF-alpha and
      increase Akt/PI3K expression, which are relative to key species of gut
      microbiota. CONCLUSION: STS decreases pancreatic mRNA expression of IL-6 and TNF
      alpha via key species of gut microbiota. The mechanism of this effect is similar
      to that of MET.

PMID- 29341444
TI  - Teaching clinical leadership to medical students.

PMID- 29341445
TI  - Automated detection of preserved photoreceptor on optical coherence tomography in
      choroideremia based on machine learning.
AB  - Optical coherence tomography (OCT) can demonstrate early deterioration of the
      photoreceptor integrity caused by inherited retinal degeneration diseases (IRDs).
      A machine learning method based on random forests was developed to automatically
      detect continuous areas of preserved ellipsoid zone structure (an easily
      recognizable part of the photoreceptors on OCT) in 16 eyes of patients with
      choroideremia (a type of IRD). Pseudopodial extensions protruding from the
      preserved ellipsoid zone areas are detected separately by a local active contour
      routine. The algorithm is implemented on en face images with minimum segmentation
      requirements, only needing delineation of the Bruch's membrane, thus evading the
      inaccuracies and technical challenges associated with automatic segmentation of
      the ellipsoid zone in eyes with severe retinal degeneration.

PMID- 29341446
TI  - Carboxytherapy for treatment of localized chronic plaque psoriasis: Clinical and
      histopathologic evaluation.
AB  - BACKGROUND: Multiple treatment options are introduced in treatment of chronic
      localized plaque psoriasis but with poor adherence and poor patients'
      satisfaction resulting in poor treatment outcome. OBJECTIVE: In this pilot study,
      we investigated the safety and efficacy of carboxytherapy in treatment of chronic
      localized plaque psoriasis. METHODS: Thirty adult patients with chronic localized
      plaque psoriasis were enrolled in this study. The patients received
      carboxytherapy injection once/week for 8 weeks. Patients were clinically and
      histpathologically evaluated 2 weeks after the last treatment. Clinical response
      was evaluated by investigator's global assessment, total sign score, and 5-point
      scale for perilesional erythema. We performed 10-point visual analog scale for
      patient's satisfaction, and side effects. Three months after the last session we
      evaluate recurrence using 10-point scale. RESULTS: Carboxytherapy achieved
      treatment success in 26.6% according to investigator's global assessment and
      total sign score and 70% of the patients demonstrated absence of perilesional
      erythema. Patients were satisfied with no reported side effects. Recurrence area
      was within 1% -10% of the baseline area in 83.3% of the improved patients.

PMID- 29341447
TI  - Anti-transcription intermediary factor 1gamma antibody titer correlates with
      clinical symptoms in a patient with recurrent dermatomyositis associated with
      ovarian cancer.

PMID- 29341448
TI  - Beneficial actions of microbiota-derived tryptophan metabolites.
AB  - Tryptophan is an important dietary amino acid and it is the precursor for 5
      hydroxytryptamine synthesis in the nervous system and by enterochromaffin cells
      in the gut mucosa. Tryptophan is also metabolized by enzymes in the gut mucosa
      and also by enzymes produced by the gut microbiome. Diet and the microbiome can
      contribute to metabolic disease in part by causing intestinal inflammation and
      increased permeability. In this issue of Neurogastroenterology and Motility,
      Jennis et al. test the hypothesis that indole tryptophan metabolites produced by
      gut bacteria might be responsible for the anti-inflammatory and beneficial
      metabolic effects of the gut microbiome and Roux-en-Y gastric bypass surgery for
      weight loss by obese patients. The authors identified indole-3-propionic acid as
      the beneficial metabolite. A review of the literature also revealed the
      beneficial effects of tryptophan metabolites on diabetes and metabolic disease
      and on inflammatory bowel disease. Taken together, these data highlight another
      health benefit of the intestinal microbiome, which produces beneficial products
      from dietary amino acids especially tryptophan.

PMID- 29341449
TI  - Digging deeper: A holistic perspective of factors affecting soil organic carbon
      sequestration in agroecosystems.
AB  - The global magnitude (Pg) of soil organic carbon (SOC) is 677 to 0.3-m, 993 to
      0.5-m, and 1,505 to 1-m depth. Thus, ~55% of SOC to 1-m lies below 0.3-m depth.
      Soils of agroecosystems are depleted of their SOC stock and have a low use
      efficiency of inputs of agronomic yield. This review is a collation and synthesis
      of articles published in peer-reviewed journals. The rates of SOC sequestration
      are scaled up to the global level by linear extrapolation. Soil C sink capacity
      depends on depth, clay content and mineralogy, plant available water holding
      capacity, nutrient reserves, landscape position, and the antecedent SOC stock.
      Estimates of the historic depletion of SOC in world soils, 115-154 (average of
      135) Pg C and equivalent to the technical potential or the maximum soil C sink
      capacity, need to be improved. A positive soil C budget is created by increasing
      the input of biomass-C to exceed the SOC losses by erosion and mineralization.
      The global hotspots of SOC sequestration, soils which are farther from C
      saturation, include eroded, degraded, desertified, and depleted soils. Ecosystems
      where SOC sequestration is feasible include 4,900 Mha of agricultural land
      including 332 Mha equipped for irrigation, 400 Mha of urban lands, and ~2,000 Mha
      of degraded lands. The rate of SOC sequestration (Mg C ha-1  year-1 ) is 0.25-1.0
      in croplands, 0.10-0.175 in pastures, 0.5-1.0 in permanent crops and urban lands,
      0.3-0.7 in salt-affected and chemically degraded soils, 0.2-0.5 in physically
      degraded and prone to water erosion, and 0.05-0.2 for those susceptible to wind
      erosion. Global technical potential of SOC sequestration is 1.45-3.44 Pg C/year
      (2.45 Pg C/year).

PMID- 29341450
TI  - Characterization of a novel, papain-inducible murine model of eosinophilic
      rhinosinusitis.
AB  - BACKGROUND: Eosinophilic chronic rhinosinusitis (ECRS) is a disease characterized
      by eosinophilic inflammatory infiltrate and a local type 2 cytokine milieu.
      Current animal models fail to recapitulate many of the innate and adaptive
      immunologic hallmarks of the disease, thus hindering the development of effective
      therapeutics. In the present study, mice were exposed intranasally to the
      cysteine protease papain, which shares functional similarities with parasitic
      proteases and aeroallergens, to generate a rapidly inducible murine model of
      eosinophilic rhinosinusitis. METHODS: C57BL/6 mice were intranasally instilled
      with 20 MUg papain or heat-inactivated papain (HP) on days 0-2 and days 7-10, and
      then euthanized on day 11. Nasal lavage fluid (NALF) was analyzed to quantify
      eosinophils and inflammatory cytokine secretion. Sinonasal tissue was sectioned
      and stained for goblet cells or homogenized to analyze cytokine levels. Serum
      samples were assayed for immunoglobulin E (IgE) by enzyme-linked immunoassay.
      Sinonasal mucosal tissue was dissociated and analyzed by flow cytometry. RESULTS:
      Compared with HP treatment, papain induced significant eosinophilia in NALF,
      goblet cell hyperplasia, innate and adaptive immune cell infiltration, type 2
      cytokine production, and IgE responses. Flow cytometric analysis of sinonasal
      tissues revealed significant inflammatory cell infiltration and interleukin-13
      producing cell populations. CONCLUSION: In this study, we demonstrated that the
      cysteine protease papain induces allergic sinonasal eosinophilic rhinosinusitis
      and resembles T-helper 2 cell inflammation and innate immune characteristics of
      ECRS. This model permits further study into the molecular mechanisms underlying
      ECRS pathology and provides a model system for the evaluation of potential
      pharmacologic interventions.

PMID- 29341451
TI  - Exophytic sinonasal papillomas and nasal florid papillomatosis: A retrospective
      study.
AB  - BACKGROUND: Sinonasal exophytic papillomas are rare. The multifocal form, florid
      papillomatosis, has not been yet described in literature. We report on the
      clinical features and the management of the different forms of exophytic
      papilloma. METHODS: A retrospective study was conducted that included all
      patients with exophytic papilloma treated in our center over the past 12 years.
      We recorded clinical presentation, treatments, recurrences, pathology (p16
      expression and human papillomavirus [HPV] status). RESULTS: We included 13
      patients with a mean follow-up of 5 years. The main location of exophytic
      papilloma was the anterior part of the septum. Lesions were multifocal in 3
      patients corresponding to florid papillomatosis. The main treatment was surgery.
      Cases of HPV-11 or HPV-6 were present in all forms of exophytic papilloma
      (dysplasia in 4 cases). Late recurrences occurred in 3 patients (2 patients with
      florid papillomatosis) over a period of 3 years. CONCLUSION: Exophytic papilloma
      has 2 clinical presentations: localized and diffuse. Patients with florid
      papillomatosis should be monitored closely as recurrence seems to be frequent.

PMID- 29341452
TI  - Contribution of MLH1 constitutional methylation for Lynch syndrome diagnosis in
      patients with tumor MLH1 downregulation.
AB  - Constitutional epimutation of the two major mismatch repair genes, MLH1 and MSH2,
      has been identified as an alternative mechanism that predisposes to the
      development of Lynch syndrome. In the present work, we aimed to investigate the
      prevalence of MLH1 constitutional methylation in colorectal cancer (CRC) patients
      with abnormal expression of the MLH1 protein in their tumors. In a series of 38
      patients who met clinical criteria for Lynch syndrome genetic testing, with loss
      of MLH1 expression in the tumor and with no germline mutations in the MLH1 gene
      (35/38) or with tumors presenting the BRAF p.Val600Glu mutation (3/38), we
      screened for constitutional methylation of the MLH1 gene promoter using
      methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA)
      in various biological samples. We found four (4/38; 10.5%) patients with
      constitutional methylation in the MLH1 gene promoter. RNA studies demonstrated
      decreased MLH1 expression in the cases with constitutional methylation when
      compared with controls. We could infer the mosaic nature of MLH1 constitutional
      hypermethylation in tissues originated from different embryonic germ layers, and
      in one family we could show that it occurred de novo. We conclude that
      constitutional MLH1 methylation occurs in a significant proportion of patients
      who have loss of MLH1 protein expression in their tumors and no MLH1 pathogenic
      germline mutation. Furthermore, we provide evidence that MLH1 constitutional
      hypermethylation is the molecular mechanism behind about 3% of Lynch syndrome
      families diagnosed in our institution, especially in patients with early onset or
      multiple primary tumors without significant family history.

PMID- 29341453
TI  - Mechanism underlying the negative effect of prostate volume on the outcome of
      extensive transperineal ultrasound-guided template prostate biopsy.
AB  - Previous studies have indicated a possible relationship between increased
      prostate volume (PV) and decreased biopsy yield, although the mechanism involved
      is unclear. We evaluated 1650 patients who underwent template biopsy. The
      distribution of 993 cancer lesions in 302 prostatectomy specimens was compared
      with the biopsy data to determine whether each lesion was detected. A receiver
      operating characteristic (ROC) model was used to determine the diagnostic
      accuracy of prostate-specific antigen (PSA) and related markers. A medical record
      number (MRN) was used as a negative control. The cancer positive rate did not
      change as PSA increased in patients with PV >=50 mL (P = 0.466), although it
      increased as PSA increased in patients with PV<50 mL (P = 0.001). The detection
      rate of cancer lesions decreased as the diameter of the lesions decreased (P =
      0.018), but remained unchanged with respect to PV. The diameters of the maximum
      lesions in patients with PV >= 50 mL were significantly smaller than those in
      patients with PV<50 mL (P = 0.003). In patients with PV >= 50 mL, the areas under
      the ROC curves for PSA-related markers did not differ significantly from that for
      MRN, although they were significantly greater than that for MRN in patients with
      PV<50 mL (P < 0.001). These results suggest that an increase in PV is associated
      with a decrease in size and detectability of cancer lesions resulting in a
      decrease in biopsy yield. Loss of diagnostic accuracy of markers in patients with
      PV >= 50 mL indicates a decrease in serum levels of PSA produced by prostate
      cancer, which suggests growth inhibition of the cancer.

PMID- 29341454
TI  - Socioeconomic deprivation and the burden of head and neck cancer-Regional
      variations of incidence and mortality in Merseyside and Cheshire, North West,
      England.
AB  - OBJECTIVES: The aim of this longitudinal study was to examine the distribution of
      head and neck cancer (HANC) disease burden across the region comparing it to
      national trends. DESIGN: We undertook a retrospective study of routine data
      combining it with indicators of deprivation and lifestyle at small geographical
      areas within the 9 Local Authorities (LAs) of Merseyside and Cheshire Network
      (MCCN) for head and neck cancers. Data from the North West of England and England
      were used as comparator regions. SETTING: This research was undertaken by the
      Cheshire and Merseyside Public Health Collaborative, UK. PARTICIPANTS: The
      Merseyside and Cheshire region serves a population of 2.2 million. Routine data
      allowed us to identify HANC patients diagnosed with cancers coded ICD C00-C14 and
      C30-C32 within 3 cohorts 1998-2000, 2008-2010 and 2009-2011 for our analysis.
      MAIN OUTCOME MEASURES: Directly age-standardised incidence rates and directly age
      standardised mortality rates in the LAs and comparator regions were measured.
      Lifestyle and deprivation indicators were plotted against them and measured by
      Pearson's correlation coefficients. RESULTS: The incidence of head and neck
      cancer has increased across the region from 1998-2000 to 2008-2010 with a peak
      incidence for Liverpool males at 35/100 000 population. Certain Middle Super
      Output Areas contribute disproportionately to the significant effect of incidence
      and mortality within LAs. Income deprivation had the strongest correlation with
      incidence (r = .59) and mortality (r = .53) of head and neck cancer. CONCLUSION:
      Our study emphasises notable geographical variations within the region which need
      to be addressed through public health measures.

PMID- 29341455
TI  - Microsatellite markers for evaluating the diversity of the natural killer complex
      and major histocompatibility complex genomic regions in domestic horses.
AB  - Genotyping microsatellite markers represents a standard, relatively easy, and
      inexpensive method of assessing genetic diversity of complex genomic regions in
      various animal species, such as the major histocompatibility complex (MHC) and/or
      natural killer cell receptor (NKR) genes. MHC-linked microsatellite markers have
      been identified and some of them were used for characterizing MHC polymorphism in
      various species, including horses. However, most of those were MHC class II
      markers, while MHC class I and III sub-regions were less well covered. No tools
      for studying genetic diversity of NKR complex genomic regions are available in
      horses. Therefore, the aims of this work were to establish a panel of markers
      suitable for analyzing genetic diversity of the natural killer complex (NKC), and
      to develop additional microsatellite markers of the MHC class I and class III
      genomic sub-regions in horses. Nine polymorphic microsatellite loci were newly
      identified in the equine NKC. Along with two previously reported microsatellites
      flanking this region, they constituted a panel of 11 loci allowing to
      characterize genetic variation in this functionally important part of the horse
      genome. Four newly described MHC class I/III-linked markers were added to 11
      known microsatellites to establish a panel of 15 MHC markers with a better
      coverage of the class I and class III sub-regions. Major characteristics of the
      two panels produced on a group of 65 horses of 13 breeds and on five Przewalski's
      horses showed that they do reflect genetic variation within the horse species.

PMID- 29341456
TI  - Iron pill aspiration: Cytologic and histologic findings of a potential life
      threatening airway injury. A Case report and literature review.
AB  - Iron pill-induced injury of bronchial mucosa is a complication following
      accidental aspiration of an iron tablet. Oral iron supplementation is a common
      therapy, particularly among advanced-age patients, who are more prone to
      aspiration. However, iron pill aspiration has been rarely reported in the
      literature, usually under the format of short case reports, with only 32 cases
      published in the literature. The cytologic features suspicious for this rare but
      potentially lethal entity have been seldom described. We report a case of a
      patient diagnosed with iron pill-induced bronchial injury, after oral ferrous
      sulfate has been prescribed during a hospital admission for pneumonia. In the
      bronchial washing specimen, a background of necrotic cell debris and acute
      inflammation involving extracellular golden-brown fibrils positive for iron
      stains was seen, along with the yeast forms, which, in this clinical context
      could confirm the iron pill aspiration. Our aim is to highlight the cytology
      features associated with iron pill aspiration bronchitis, and to review the
      literature for the histologic, clinical, bronchoscopy, and treatment aspects.

PMID- 29341457
TI  - Different effects of dexmedetomidine and midazolam on the expression of NR2B and
      GABAA-alpha1 following peripheral nerve injury in rats.
AB  - Neuropathic pain is a complex, chronic pain condition and the treatment is a
      major clinical challenge. Recent studies have shown that two FDA approved drugs
      dexmedetomidine (DEX) and midazolam (MZL), may be useful in treating neuropathic
      pain, but the mechanism is not fully dementated. Here, we investigated the
      effects and mechanisms of DEX and MZL treatment in the peripheral nerve injury
      model. Intramuscular injection with DEX and MZL attenuated the development of
      mechanical allodynia and thermal hyperalgesia in rats with chronic constriction
      injury (CCI). Concurrently, the expression of NMDA receptor subunit 2B (NR2B),
      GABA (A) receptor subunit alpha1 (GABAA-alpha1), and Sonic Hedgehog (SHH)
      displayed different temporal patterns in the thalamus and the ipsilateral dorsal
      horn of the spinal cord after CCI. Such that (1) NR2B expression was decreased on
      day 1 and 14, whereas GABAA-alpha1 expression was increased on day 1 in the
      thalamus, and NR2B expression was decreased on day 1, whereas GABAA-alpha1
      expression was increased on day 1 and day 30 in the ipsilateral spinal cord
      dorsal horn after DEX treatment. (2) NR2B expression was increased on day 1, then
      decreased on day 14 and returned to baseline on day30, whereas GABAA-alpha1
      expression was no significant changes on day 1, 14, 30 in the thalamus, and NR2B
      expression was decreased on day 14 and 30, whereas GABAA-alpha1 expression was no
      changes on day 1 and 14 but increased on day 30 after MZL treatment. Furthermore,
      the mechanical allodynia was significantly attenuated after PUR administration.
      Meanwhile the expression of NR2B was significantly decreased, and the expression
      of GABAA-alpha1 was significantly increased, in the thalamus and in the
      ipsilateral spinal cord dorsal horn when detected on postoperative day 1, 7, and
      14. Our findings indicate that DEX and MZL have different mechanisms in CCI rats,
      suggesting different strategies could be considered in managing neuropathic pain
      in different individuals. (c) 2018 IUBMB Life, 70(2):143-152, 2018.

PMID- 29341458
TI  - Procedural competency in emergency medicine training.

PMID- 29341460
TI  - Intellectual disability and epilepsy due to the K/L-mediated Xq28 duplication:
      Further evidence of a distinct, dosage-dependent phenotype.
AB  - Copy number variants of the X-chromosome are a common cause of X-linked
      intellectual disability in males. Duplication of the Xq28 band has been known for
      over a decade to be the cause of the Lubs X-linked Mental Retardation Syndrome
      (OMIM 300620) in males and this duplication has been narrowed to a critical
      region containing only the genes MECP2 and IRAK1. In 2009, four families with a
      distal duplication of Xq28 not including MECP2 and mediated by low-copy repeats
      (LCRs) designated "K" and "L" were reported with intellectual disability and
      epilepsy. Duplication of a second more distal region has been described as the
      cause of the Int22h-1/Int22h-2 Mediated Xq28 Duplication Syndrome, characterized
      by intellectual disability, psychiatric problems, and recurrent infections. We
      report two additional families possessing the K/L-mediated Xq28 duplication with
      affected males having intellectual disability and epilepsy similar to the
      previously reported phenotype. To our knowledge, this is the second cohort of
      individuals to be reported with this duplication and therefore supports K/L
      mediated Xq28 duplications as a distinct syndrome.

PMID- 29341459
TI  - Multicenter study of diagnostic procedures, genetic aberration analysis, and
      first-line treatment of lung cancer in Jiangsu Province, China.
AB  - BACKGROUND: Jiangsu Province, China, is highly developed economically and
      culturally, and has a high prevalence of lung cancer. We aimed to evaluate the
      diagnostic procedures, genetic aberration analysis status, and first-line
      treatment models of lung cancer in Jiangsu Province. METHODS: Lung cancer
      patients diagnosed in 2016 at 22 tertiary care hospitals were evaluated.
      Demographic characteristics, tumor histology, staging, family history of lung
      cancer, auxiliary examinations, genetic testing, and first-line treatment were
      collected on discharge. Diagnostic and treatment data were analyzed by
      descriptive statistics. RESULTS: A total of 928 patients were enrolled. Chest
      computed tomography was the most frequently used diagnostic method; pathology
      diagnosis was carried out by transbronchial lung biopsy and transthoracic needle
      aspiration. Stage T1-2N0M0 small-cell lung cancer patients experienced surgical
      resection, and others received cisplatin and etoposide chemotherapy. Stage I and
      stage II non-small cell lung cancer patients experienced surgical resection;
      stage III and stage IV patients received cisplatin and pemetrexed chemotherapy as
      first-line treatment. Detection of epidermal growth factor receptor (EGFR)
      mutations occurred in 29.9% of non-selective, 36.5% of locally advanced or
      metastatic, and 42.1% of advanced non-squamous non-small cell lung cancer. The
      overall EGFR-positive rates were 49.0%, 52.5%, and 53.9%. A total 72.0% of
      patients with EGFR mutations were treated with tyrosine kinase inhibitors.
      CONCLUSION: Chest computed tomography was the most commonly performed diagnostic
      method for lung cancer. First-line treatment was primarily determined by disease
      stages and EGFR mutation status, with few expectations.

PMID- 29341461
TI  - Effect of immediate and prolonged GLP-1 receptor agonist administration on uric
      acid and kidney clearance: Post-hoc analyses of four clinical trials.
AB  - AIMS: To determine the effects of glucagon-like peptide (GLP)-1 receptor agonists
      (RA) on uric acid (UA) levels and kidney UA clearance. MATERIAL AND METHODS: This
      study involved post-hoc analyses of 4 controlled clinical trials, which assessed
      actions of GLP-1RA administration on kidney physiology. The immediate effects of
      GLP-1RA exenatide infusion vs placebo were determined in 9 healthy overweight men
      (Study-A) and in 52 overweight T2DM patients (Study-B). The effects of 12 weeks
      of long-acting GLP-1RA liraglutide vs placebo in 36 overweight T2DM patients
      (Study-C) and of 8 weeks of short-acting GLP-1RA lixisenatide vs once-daily
      titrated insulin glulisine in 35 overweight T2DM patients (Study-D) were also
      examined. Plasma UA, fractional (inulin-corrected) and absolute urinary excretion
      of UA (UEUA ) and sodium (UENa ), and urine pH were determined. RESULTS: Median
      baseline plasma UA level was 5.39 to 6.33 mg/dL across all studies (17%-22% of
      subjects were hyperuricaemic). In Study-A, exenatide infusion slightly increased
      plasma UA (+0.07 +/- 0.02 mg/dL, P = .04), and raised absolute-UEUA (+1.58 +/-
      0.65 mg/min/1.73 m2 , P = .02), but did not affect fractional UEUA compared to
      placebo. Fractional UEUA and absolute UEUA correlated with increases in urine pH
      (r:0.86, P = .003 and r:0.92, P < .001, respectively). Fractional UEUA correlated
      with increased fractional UENa (r:0.76, P = .02). In Study-B, exenatide infusion
      did not affect plasma UA, but increased fractional UEUA (+0.76 +/- 0.38%, P =
      .049) and absolute UEUA (+0.75 +/- 0.27 mg/min/1.73 m2 , P = .007), compared to
      placebo. In regression analyses, both parameters were explained by changes in
      urine pH and, in part, by changes in UENa . In Study-C, liraglutide treatment did
      not affect plasma UA, UEUA, UENa or urine pH, compared to placebo. In Study-D,
      lixisenatide treatment increased UENa and urine pH from baseline, but did not
      affect plasma UA or UEUA . CONCLUSION: Immediate exenatide infusion increases
      UEUA in overweight healthy men and in T2DM patients, probably by inhibiting Na+
      /H+ -exchanger type-3 in the renal proximal tubule. Prolonged treatment with a
      long-acting or short-acting GLP-1RA does not affect plasma UA or UEUA in T2DM
      patients with normal plasma UA levels and at relatively low cardiovascular risk.
      Our results suggest that the cardio-renal benefits of GLP-1RA are not mediated
      through changes in UA.

PMID- 29341462
TI  - DNA Origami Scaffolds as Templates for Functional Tetrameric Kir3 K+ Channels.
AB  - In native systems, scaffolding proteins play important roles in assembling
      proteins into complexes to transduce signals. This concept is yet to be applied
      to the assembly of functional transmembrane protein complexes in artificial
      systems. To address this issue, DNA origami has the potential to serve as
      scaffolds that arrange proteins at specific positions in complexes. Herein, we
      report that Kir3 K+ channel proteins are assembled through zinc-finger protein
      (ZFP)-adaptors at specific locations on DNA origami scaffolds. Specific binding
      of the ZFP-fused Kir3 channels and ZFP-based adaptors on DNA origami were
      confirmed by atomic force microscopy and gel electrophoresis. Furthermore, the
      DNA origami with ZFP binding sites nearly tripled the K+ channel current activity
      elicited by heterotetrameric Kir3 channels in HEK293T cells. Thus, our method
      provides a useful template to control the oligomerization states of membrane
      protein complexes in vitro and in living cells.

PMID- 29341463
TI  - Synthetic phonics and decodable instructional reading texts: How far do these
      support poor readers?
AB  - This paper presents data from a quasi-experimental trial with paired
      randomisation that emerged during the development of a reading scheme for
      children in England. This trial was conducted with a group of 12 children, aged 5
      6, and considered to be falling behind their peers in reading ability and a
      matched control group. There were two intervention conditions (A: using mixed
      teaching methods and a high percentage of non-phonically decodable vocabulary; P:
      using mixed teaching methods and low percentage of non-decodable vocabulary);
      allocation to these was randomised. Children were assessed at pre- and post-test
      on standardised measures of receptive vocabulary, phoneme awareness, word
      reading, and comprehension. Two class teachers in the same school each selected 6
      children, who they considered to be poor readers, to participate (n = 12). A
      control group (using synthetic phonics only and phonically decodable vocabulary)
      was selected from the same 2 classes based on pre-test scores for word reading (n
      = 16). Results from the study show positive benefits for poor readers from using
      both additional teaching methods (such as analytic phonics, sight word
      vocabulary, and oral vocabulary extension) in addition to synthetic phonics, and
      also non-decodable vocabulary in instructional reading text.

PMID- 29341464
TI  - Left sleeve lobectomy versus left pneumonectomy for the management of patients
      with non-small cell lung cancer.
AB  - BACKGROUND: The study was conducted to compare the outcomes of sleeve lobectomy
      (SL) and pneumonectomy (PN) for management of the left lung in patients with non
      small cell lung cancer (NSCLC). METHODS: One hundred and thirty-five patients who
      underwent left SL (n = 87) or left PN (n = 48) for NSCLC from January 2006 to
      December 2011 were enrolled in this retrospective study. Left SL was performed
      when technically possible. The clinicopathological features and treatment
      outcomes in both groups were compared. Survival was evaluated using the Kaplan
      Meier method, and significant differences were calculated using the log-rank
      test. Multivariate analysis was conducted using the Cox proportional hazards
      model to analyze significant variables associated with the outcomes of left SL.
      RESULTS: There were no significant differences in general clinicopathological
      features (age, gender, lymph node metastasis, pathological stage, and
      complications of bronchial fistula) between patients who underwent left SL and
      left PN. The operation duration was markedly longer and the extent of bleeding
      was greater for left SL than left PN; however patients who underwent left SL
      achieved significantly longer overall survival than patients who underwent left
      PN. The outcomes of left SL were only associated with pathological stage.
      CONCLUSIONS: Our results indicate that left SL may offer superior survival than
      left PN in selected patients. If anatomically feasible, left SL may be a
      preferred alternative to left PN for NSCLC patients. Pathological stage is an
      important factor to determine the outcome of SL.

PMID- 29341465
TI  - P2Y12 deficiency in mouse impairs noradrenergic system in brain, and alters
      anxiety-like neurobehavior and memory.
AB  - Purinergic receptor P2Y12 (P2Y12 ), a G protein-coupled purinergic receptor, is
      widely distributed in nervous system and involved in the progression of
      neurological diseases such as multiple sclerosis and neuropathic pain. The
      central noradrenergic system actively participates in a number of
      neurophysiological processes. Nevertheless, whether there is any direct relevance
      between P2Y12 and noradrenergic signal transduction remains unknown. In the
      present study, we tested the hypothesis that lack of P2Y12 impaired noradrenergic
      signal transduction in mouse brain. Our results showed that P2Y12 knockout (KO)
      mice exhibited increased anxiety-like behavior in the open-field test (OFT) and
      elevated plus maze test and displayed deficits in memory in the radial-arm maze
      test (RAMT) and Morris water maze test (MWMT). They also exhibited reduced
      locomotion in the OFT and MWMT. Moreover, loss of P2Y12 decreased the level of
      noradrenaline and the expression of noradrenergic alpha receptors, subtypes
      alpha2 (ARalpha2b) in mouse cerebellum and hippocampus. Meanwhile, it hampered
      the protein kinase A (PKA)/cAMP response element-binding protein (CREB)/brain
      derived neurotrophic factor (BDNF) signaling pathway in these brain regions.
      Taken together, our results showed for the first time that P2Y12 KO altered the
      anxiety, memory and locomotion of mice, which was closely associated with
      abnormal state of noradrenergic system in the brain. The findings implicate that
      P2Y12 plays an indispensable role in noradrenergic signal transduction; its
      deficit is insufficient to limit anxiety responses or supports cognitive
      performance and activity.

PMID- 29341466
TI  - Effects of intravenous home dobutamine in palliative end-stage heart failure on
      quality of life, heart failure hospitalization, and cost expenditure.
AB  - AIMS: In patients with palliative end-stage heart failure, interventions that
      could provide symptomatic relief and prevent hospital admissions are important.
      Ambulatory continuous intravenous inotropes have been advocated by guidelines for
      such a purpose. We sought to determine the effect of intravenous dobutamine on
      symptomatic status, hospital stay, mortality, and cost expenditure. METHODS AND
      RESULTS: All consecutive end-stage heart failure patients not amenable for
      advanced therapies and discharged with continuous intravenous home dobutamine
      from a single tertiary centre between April 2011 and January 2017 were
      retrospectively analysed. Dobutamine (fixed dose) was infused through a single
      lumen central venous catheter with a small pump that was refilled by a nurse on a
      daily basis. Symptomatic status was longitudinally assessed as the change in New
      York Heart Association class and patient global assessment scale. Antecedent and
      incident heart failure hospitalizations were determined in a paired fashion, and
      cost impact was assessed. A total of 21 patients (age 77 +/- 9 years) were
      followed up for 869 +/- 647 days. At first follow-up (6 +/- 1 weeks) after the
      initiation of dobutamine, patients had a significant improvement in New York
      Heart Association class (-1.29 +/- 0.64; P < 0.001), global assessment scale
      (<0.001), and N-terminal pro-brain natriuretic peptide (6247 vs. 2543 pg/mL; P =
      0.033). Incident heart failure hospitalizations assessed at 3, 6, and 12 months
      were significantly reduced (P < 0.001 for all) in comparison with antecedent
      heart failure hospitalizations over the same time period. Cost expenditure was
      significantly lower at 3 (P < 0.001), 6 (P = 0.005), and 12 months (P = 0.001)
      after initiation of dobutamine. Mortality rate at 1 year was 48% with 9/12 (75%)
      patients dying at home, most often from progressive pump failure. CONCLUSIONS:
      Continuous intravenous home dobutamine in patients with palliative end-stage
      heart failure is feasible and associated with improved symptomatic status, heart
      failure hospitalizations, and health-care-related costs. Nevertheless, results
      should be interpreted in the context of the small and retrospective design.
      Larger studies are necessary to evaluate the effect of dobutamine in palliative
      end-stage heart failure.

PMID- 29341467
TI  - Optoacoustic sensing of hematocrit to improve the accuracy of hybrid fluorescence
      ultrasound intravascular imaging.
AB  - Hybrid intravascular fluorescence-ultrasound imaging is emerging for reading
      anatomical and biological information in vivo. By operating through blood,
      intravascular near-infrared fluorescence (NIRF) detection is affected by
      hemoglobin attenuation. Improved quantification has been demonstrated with
      methods that correct for the attenuation of the optical signal as it propagates
      through blood. These methods assume an attenuation coefficient for blood and
      measure the distance between detector and the vessel wall by observing the
      intravascular ultrasound images. Assumptions behind the attenuation employed in
      correction models may reduce the accuracy of these methods. Herein, we explore a
      novel approach to dynamically estimate optical absorption by using optoacoustic
      (photoacoustic) measurements. Adaptive correction is based on a trimodal
      intravascular catheter that integrates fluorescence, ultrasound and optoacoustic
      measurements. Using the novel catheter, we show how optoacoustic measurements can
      determine variations of blood absorption, leading to accurate quantification of
      the detected NIRF signals at different hematocrit values.

PMID- 29341468
TI  - Downregulation of BarH-like homeobox 2 promotes cell proliferation, migration and
      aerobic glycolysis through Wnt/beta-catenin signaling, and predicts a poor
      prognosis in non-small cell lung carcinoma.
AB  - BACKGROUND: Human BarH-like homeobox 2 (Barx2), a homeodomain factor of the Bar
      family, plays a critical role in cell adhesion and cytoskeleton remodeling, and
      has been reported in an increasing array of tumor types except non-small cell
      lung carcinoma (NSCLC). The purpose of the current study was to characterize the
      expression of Barx2 and assess the clinical significance of Barx2 in NSCLC.
      METHODS: Quantitative real-time polymerase chain reaction, immunohistochemistry
      and western blot analysis were used to examine mRNA and protein expression,
      respectively. The relationships between Barx2 expression and clinicopathological
      variables were analyzed. Cell Counting Kit-8 and plate colony formation assay
      were used to detect cell proliferation. Transwell assay was used to examine cell
      migration ability. Glucose uptake, lactate, adenosine triphosphate, and lactate
      dehydrogenase assays were used to detect aerobic glycolysis. RESULTS: Barx2 is
      downregulated in NSCLC tissues compared with para-carcinoma. Furthermore, Barx2
      expression shows a negative correlation with advanced TNM stage and a high level
      of Ki-67. Survival analysis reveals that Barx2 level is an independent prognostic
      factor for NSCLC patients. The Barx2 (low) Ki-67 (high) group had the worst
      prognosis. Furthermore, the data indicate that downregulation of Barx2 expression
      promotes cell proliferation, migration, and aerobic glycolysis, including
      increased lactate dehydrogenase activity, glucose utilization, lactate
      production, and decreased intracellular adenosine triphospahte level.
      Furthermore, Barx2 acts as a negative regulator of the canonical Wnt/beta-catenin
      pathway. Reactivation of Wnt/beta-catenin pathway by LiCl can reverse the
      inhibiting effect of Barx2. CONCLUSIONS: These findings reveal that Barx2 serving
      as a tumor suppressor gene could decrease cell proliferation, migration, and
      aerobic glycolysis through inhibiting the Wnt/beta-catenin signaling pathway, and
      predicts a good prognosis in NSCLC.

PMID- 29341469
TI  - Downregulation of CSN6 attenuates papillary thyroid carcinoma progression by
      reducing Wnt/beta-catenin signaling and sensitizes cancer cells to FH535 therapy.
AB  - The incidence of thyroid cancer has increased worldwide at a rate higher than
      that of any other cancer. CSN6 is overexpressed in many types of cancers, and
      such expression is linked to oncogenic activity. However, the detailed biological
      functions of CSN6 in papillary thyroid cancer (PTC) have not been well
      characterized. We investigated CSN6 expression in PTC specimens and cell lines.
      We used short-hairpin RNA-mediated gene silencing to explore the biological
      effects of CSN6 depletion in PTC cells. The combined effects of CSN6 silencing
      and FH535 therapy were assessed in terms of cell viability. The mechanism by
      which CSN6 regulated beta-catenin expression was also analyzed. CSN6 levels were
      determined by real-time polymerase chain reaction (PCR) (mRNA), Western blotting,
      and immunochemistry (protein). The CCK-8 and migration assays and orthotopic
      xenograft transplantation were used to investigate the biological effects of
      CSN6. We assessed the combined effects of CSN6 silencing and FH535 on cell
      viability in vitro. We also analyzed the relationship between the CSN6 level and
      clinical pathological status. CSN6 was overexpressed in human PTCs, and loss of
      CSN6 attenuated tumor proliferation and migration both in vitro and in vivo. CSN6
      stabilized beta-catenin and facilitated the epidermal-to-mesenchymal transition
      (EMT) in PTC cells. CSN6 positively regulated beta-catenin expression in a beta
      Trcp-dependent manner and triggered expression of several EMT-related genes
      regulated by beta-catenin. CSN6 silencing sensitized PTC cells to FH535 therapy
      via downregulation of the Wnt/beta-catenin signaling pathway. Finally, in PTC
      patients, the level of CSN6 was significantly (inversely) correlated with tumor
      size, the presence of multifocal lesions, and TNM stage. CSN6 overexpression in
      PTC is a strong indicator of enhanced tumor aggressiveness. CSN6 promotes PTC
      progression by inducing the EMT. CSN6 knockdown sensitizes PTC cells to FH535
      therapy via downregulation of the Wnt/beta-catenin signaling pathway.

PMID- 29341470
TI  - Cytological features of mixed adenoneuroendocrine carcinoma of the ampulla of
      Vater: A case report with immunocytochemical analyses.
AB  - Mixed adenoneuroendocrine carcinoma (MANEC) is defined as a tumor that has
      morphologically recognizable both adenocarcinoma and neuroendocrine carcinoma
      components comprising at least 30% of either components. MANEC occurring in the
      ampulla of Vater is extremely rare, and only 16 cases have been reported in the
      English language literature. In the present report, we describe the first case of
      MANEC of the ampulla of Vater with immunocytochemical analyses. An 82-year-old
      Japanese male was incidentally found to have a tumorous lesion in the ampulla of
      Vater. Endoscopic ultrasound-fine needle aspiration (EUS-FNA) of the tumor was
      performed. The Papanicolaou smear demonstrated the presence of different three
      components. The most dominant component was cohesive clusters of small round
      cells with round to oval nuclei with powdery chromatin and scant cytoplasm, which
      corresponded to small cell carcinoma. The second component was an adenocarcinoma,
      which was composed of irregularly overlapping clusters of tall columnar cells
      with large round to oval nuclei containing conspicuous nucleoli. The third
      component was an adenoma, which was comprised of flat cohesive clusters of
      columnar cells without atypia. Immunocytochemical analyses demonstrated that
      synaptophysin was expressed in the small round cells, and cdx-2 was expressed in
      all three components. Accordingly, a cytodiagnosis of MANEC with adenoma
      component was made. Preoperative diagnosis of ampullary MANEC is difficult.
      However, this report clearly demonstrates three different components in the EUS
      FNA cytological specimen. Therefore, we suggest that cytological examination is a
      useful method for diagnosis of MANEC of the ampulla of Vater.

PMID- 29341472
TI  - Characterization of the novel HLA-B*40:01:31 allele.
AB  - The HLA-B*40:01:31 allele differs from B*40:01:01 by one nucleotide substitution
      at position 216.

PMID- 29341471
TI  - The impact of a dose of the angiotensin receptor blocker valsartan on post
      myocardial infarction ventricular remodelling.
AB  - AIMS: Although clinical guidelines advocate the use of the highest tolerated dose
      of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers
      after acute myocardial infarction (MI), the optimal dosing or the risk-benefit
      profile of different doses have not been fully identified. METHODS AND RESULTS:
      In this multicentre trial, 495 Korean patients with acute ST segment elevation MI
      and subnormal left ventricular (LV) ejection fraction (<50%) were randomly
      allocated (2:1) to receive maximal tolerated dose of valsartan (titrated up to
      320 mg/day, n = 333) or low-dose valsartan (80 mg/day, n = 162) treatment. The
      primary objective was to assess the changes in echocardiographic parameters of LV
      remodelling from baseline to 12 months after discharge. After treatment, end
      diastolic LV volume (LVEDV) decreased significantly in the low-dose group, but
      the difference in LVEDV changes was insignificant between the maximal-tolerated
      dose and low-dose groups. End-systolic LV volume decreased significantly in both
      groups, to a similar degree between groups. LV ejection fraction rose
      significantly in both study groups, to a similar degree. Changes in plasma levels
      of neurohormones were also comparable between the two groups. Drug-related
      adverse effects occurred more frequently in the maximal-tolerated-dose group than
      in the low-dose group (7.96 vs. 0.69%, P < 0.001). CONCLUSIONS: In the present
      study, treatment with the maximal tolerated dose of valsartan did not exhibit a
      superior effect on post-MI LV remodelling compared with low-dose treatment and
      was associated with a greater frequency of adverse effect in Korean patients.
      Further study with a sufficient number of cases and statistical power is
      warranted to verify the findings of the present study.

PMID- 29341473
TI  - Somatic mosaic deletions involving SCN1A cause Dravet syndrome.
AB  - Somatic mosaicism in single nucleotide variants of SCN1A is known to occur in a
      subset of parents of children with Dravet syndrome (DS). Here, we report
      recurrent somatic mosaic microdeletions involving SCN1A in children diagnosed
      with DS. Through the evaluation of 237 affected individuals with DS who did not
      show SCN1A or PCHD19 mutations in prior sequencing analyzes, we identified two
      children with mosaic microdeletions covering the entire SCN1A region. The allele
      frequency of the mosaic deletions estimated by multiplex ligation-dependent probe
      amplification and array comparative genomic hybridization was 25-40%, which was
      comparable to the mosaic ratio in lymphocytes and buccal mucosa cells observed by
      fluorescence in situ hybridization analysis. The minimal prevalence of SCN1A
      mosaic deletion is estimated to be 0.9% (95% confidence level: 0.11-3.11%) of DS
      with negative for SCN1A and PCDH19 mutations. This study reinforces the
      importance of somatic mosaicism caused by copy number variations in disease
      causing genes, and provides an alternative spectrum of SCN1A mutations causative
      of DS. Somatic deletions in SCN1A should be considered in cases with DS when
      standard screenings for SCN1A mutations are apparently negative for mutations.

PMID- 29341474
TI  - Effect of staining beverages on color and translucency of CAD/CAM composites.
AB  - : This study investigated the color (DeltaE) and translucency changes (DeltaTP)
      of CAD/CAM composites after exposure to staining solutions using both
      spectrophotometer and shade-matching device. Direct (Filtek Z350XT [ZT]),
      indirect (Shofu Ceramage [CE]) and CAD/CAM (Shofu HC Block [HC], Lava Ultimate
      [LU], Vita Enamic [EN]) composite specimens measuring 12 * 14 * 1.5 mm were
      fabricated, divided into five groups (n = 8), and immersed in cola, tea, coffee,
      red wine, distilled water (control) at 37 degrees C for 7 days. Color parameters
      were determined with both spectrophotometer and shade-taking device at baseline
      and 1 week. Delta E (DeltaE) with white and black backgrounds, and Delta TP
      (DeltaTP) were computed. Statistical testing was performed with ANOVA and Tukey
      post hoc test (P < .05). Mean DeltaE (white) values ranged from 0.20 +/- 0.06 to
      12.26 +/- 1.95 while mean DeltaE (black) varied from 0.22 +/- 0.11 to 14.21 +/-
      2.37. Mean DeltaTP values ranged from 0.13 +/- 0.17 to -3.87 +/- 2.16. CAD/CAM
      composites fared better in red wine than direct and indirect materials.
      Clinically perceptible color changes (DeltaE > 3.3) were observed for almost all
      materials when exposed to wine, coffee and tea. Direct, indirect, and CAD/CAM
      composites are all susceptible to various degrees of discoloration and
      translucency changes after exposure to staining beverages. Red wine caused the
      most discoloration and translucency changes. Limitations of these materials must
      be considered when placing an aesthetic restoration. CLINICAL SIGNIFICANCE:
      Direct, indirect, and CAD/CAM composites are all susceptible to various degrees
      of discoloration and translucency changes after exposure to staining beverages.
      Red wine generally caused the most discoloration and translucency changes.
      Although CAD/CAM composites were more color stable than direct and indirect
      materials when exposed to red wine, color changes were still clinically
      perceptible.

PMID- 29341475
TI  - MicroRNA-664a-5p promotes neuronal differentiation of SH-SY5Y cells.
AB  - MicroRNAs (miRNAs) belong to a class of small noncoding RNAs that play important
      roles in the translational regulation of gene expression. A number of miRNAs are
      known to act as key regulators of diverse processes such as neuronal
      differentiation. In this study, we have attempted to identify novel miRNAs
      related to neuronal differentiation via microarray analysis in the human neuronal
      differentiation model neuroblastoma SH-SY5Y cells. We identified 15 up-regulated
      and eight down-regulated miRNAs in SH-SY5Y cells treated with all-trans retinoic
      acid to induce differentiation. We further showed that one of the up-regulated
      miRNAs, miR-664a-5p, promoted neuronal differentiation of SH-SY5Y cells. These
      findings enhance our understanding of the miRNAs involved in the process of
      neurogenesis and, in particular, highlight an important role of miR-664a-5p in SH
      SY5Y cell neuronal differentiation. Further studies will be required to confirm
      the function of miR-664-5p in neuronal development and disease and to identify
      its relevant target genes.

PMID- 29341476
TI  - A rare male patient with classic Rett syndrome caused by MeCP2_e1 mutation.
AB  - Rett syndrome (RTT) is a severe neurodevelopmental disorder typically affecting
      females. It is mainly caused by loss-of-function mutations that affect the coding
      sequence of exon 3 or 4 of methyl-CpG-binding protein 2 (MECP2). Severe neonatal
      encephalopathy resulting in death before the age of 2 years is the most common
      phenotype observed in males affected by a pathogenic MECP2 variant. Mutations in
      MECP2 exon 1 affecting the MeCP2_e1 isoform are relatively rare causes of RTT in
      females, and only one case of a male patient with MECP2-related severe neonatal
      encephalopathy caused by a mutation in MECP2 exon 1 has been reported. This is
      the first reported case of a male with classic RTT caused by a 5-bp duplication
      in the open-reading frame of MECP2 exon 1 (NM_001110792.1:c.23_27dup) that
      introduced a premature stop codon [p.(Ser10Argfs*36)] in the MeCP2_e1 isoform,
      which has been reported in one female patient with classic RTT. Therefore, both
      males and females displaying at least some type of MeCP2_e1 mutation may exhibit
      the classic RTT phenotype.

PMID- 29341477
TI  - Evidence-based adequacy criteria for instrumented urine cytology using cytospin
      preparations.
AB  - Cytospin preparations of instrumented urine cytology specimens with less than 10
      urothelial cells or more than 50 urothelial cells/10 hpfs are both associated
      with significantly increased false negative rates compared to cases with 10-49
      urothelial cells/10 hpfs.

PMID- 29341478
TI  - Translational systems pharmacology-based predictive assessment of drug-induced
      cardiomyopathy.
AB  - Drug-induced cardiomyopathy contributes to drug attrition. We compared two
      pipelines of predictive modeling: (1) applying elastic net (EN) to differentially
      expressed genes (DEGs) of drugs; (2) applying integer linear programming (ILP) to
      construct each drug's signaling pathway starting from its targets to downstream
      proteins, to transcription factors, and to its DEGs in human cardiomyocytes, and
      then subjecting the genes/proteins in the drugs' signaling networks to EN
      regression. We classified 31 drugs with availability of DEGs into 13 toxic and 18
      nontoxic drugs based on a clinical cardiomyopathy incidence cutoff of 0.1%. The
      ILP-augmented modeling increased prediction accuracy from 79% to 88%
      (sensitivity: 88%; specificity: 89%) under leave-one-out cross validation. The
      ILP-constructed signaling networks of drugs were better predictors than DEGs. Per
      literature, the microRNAs that reportedly regulate expression of our six top
      predictors are of diagnostic value for natural heart failure or doxorubicin
      induced cardiomyopathy. This translational predictive modeling might uncover
      potential biomarkers.

PMID- 29341479
TI  - Nuclear division cycle 80 promotes malignant progression and predicts clinical
      outcome in colorectal cancer.
AB  - Colorectal cancer (CRC) is a common human malignancy worldwide and increasing
      studies have attributed its malignant progression to abnormal molecular changes
      in cancer cells. Nuclear division cycle 80 (NDC80) is a newly discovered
      oncoprotein that regulates cell proliferation and cycle in numerous malignancies.
      However, its clinical significance and biological role in CRC remain unclear.
      Therefore, in this study, we firstly analyze its expression in a retrospective
      cohort enrolling 224 CRC patients and find its overexpression is significantly
      correlated with advanced tumor stage and poor prognosis in CRC patients. In
      addition, our result reveals it is an independent adverse prognostic factor
      affecting CRC-specific and disease-free survival. The subgroup analysis indicates
      NDC80 expression can stratify the clinical outcome in stage II and III patients,
      but fails in stage I and IV patients. In cellular assays, we find knockdown of
      NDC80 dramatically inhibits the proliferative ability, apoptosis resistance, cell
      cycle progression, and clone formation of CRC cells in vitro. Using xenograft
      model, we further prove knockdown of NDC80 also inhibits the tumorigenic ability
      of CRC cells in vivo. Finally, the microarray analysis is utilized to
      preliminarily clarify the oncogenic molecular mechanisms regulated by NDC80 and
      the results suggest it may promote CRC progression partly by downregulating tumor
      suppressors such as dual specificity phosphatase 5 and Forkhead box O1. Taken
      together, our study provides novel evidences to support that NDC80 is not only a
      promising clinical biomarker but also a potential therapeutical target for CRC
      precise medicine.

PMID- 29341481
TI  - Sleep medication, sleep duration and healthcare utilization among older adults.

PMID- 29341482
TI  - Association between polypharmacy and clinical ward pharmacy services in hospitals
      in Tokyo.

PMID- 29341480
TI  - Cutis laxa and excessive bone growth due to de novo mutations in PTDSS1.
AB  - The cutis laxa syndromes are multisystem disorders that share loose redundant
      inelastic and wrinkled skin as a common hallmark clinical feature. The underlying
      molecular defects are heterogeneous and 13 different genes have been involved
      until now, all of them being implicated in elastic fiber assembly. We provide
      here molecular and clinical characterization of three unrelated patients with a
      very rare phenotype associating cutis laxa, facial dysmorphism, severe growth
      retardation, hyperostotic skeletal dysplasia, and intellectual disability. This
      disorder called Lenz-Majewski syndrome (LMS) is associated with gain of function
      mutations in PTDSS1, encoding an enzyme involved in phospholipid biosynthesis.
      This report illustrates that LMS is an unequivocal cutis laxa syndrome and
      expands the clinical and molecular spectrum of this group of disorders. In the
      neonatal period, brachydactyly and facial dysmorphism are two early distinctive
      signs, later followed by intellectual disability and hyperostotic skeletal
      dysplasia with severe dwarfism allowing differentiation of this condition from
      other cutis laxa phenotypes. Further studies are needed to understand the link
      between PTDSS1 and extra cellular matrix assembly.

PMID- 29341483
TI  - Use of a human-type communication robot to evaluate the categorized communicative
      ability of older adults with dementia.

PMID- 29341484
TI  - Nasal ventilation is an important factor in evaluating the diagnostic value of
      nasal nitric oxide in allergic rhinitis.
AB  - BACKGROUND: The role of nasal nitric oxide (NO) in the diagnosis of allergic
      rhinitis (AR) is controversial. The aim of this study was to identify factors
      that may affect levels of nasal NO in AR patients and evaluate the role of nasal
      NO in the diagnosis of AR. METHODS: Seventy-five AR patients and 31 healthy
      controls were enrolled in this study. AR symptom scores were assessed using the
      visual analog scale. Eosinophil cationic protein (ECP) was detected by enzyme
      linked immunoassay, nasal NO was measured using a chemiluminescence analyzer, and
      nasal airway resistance (NAR) was assessed by active anterior rhinomanometry.
      RESULTS: Nasal obstruction score, ECP, and NAR were found to be independently
      associated with nasal NO. Nasal NO level in patients with nasal obstruction score
      <7 (mild-to-moderate obstruction) was significantly increased compared with
      healthy subjects (282.1 +/- 122.6 vs 150.7 +/- 48.4 ppb; p < 0.001), and
      significantly decreased in patients with nasal obstruction score >=7 (severe
      obstruction) (97.2 +/- 52.2 vs 150.7 +/- 48.4 ppb; p < 0.001). Nasal NO and ECP
      in secretion were positively correlated in patients with mild-to-moderate nasal
      obstruction (r = 0.678), but not in patients with severe nasal obstruction (r =
      0.077). In patients with NAR <0.65 Pa/cm3 /s, the correlation coefficient was
      highest between NO and ECP (r = 0.685). The areas under the receiver operating
      characteristic curve for nasal NO level were 0.878 and 0.939 in patients with
      nasal obstruction scores <7 and NAR <0.65 Pa/cm3 /s, respectively. CONCLUSION:
      Nasal patency affects nasal NO level significantly, and may reflect the severity
      of nasal inflammation in AR patients with mild-to-moderate nasal obstruction, but
      not in patients with severe nasal obstruction.

PMID- 29341485
TI  - Development of a chemiluminescence immunoassay using recombinant non-structural
      epitope-based proteins to accurately differentiate foot-and-mouth disease virus
      infected and vaccinated bovines.
AB  - The contamination of inactivated vaccine with non-structural proteins (NSPs)
      leads to a high false-positive rate, which is a substantial barrier to accurately
      differentiate foot-and-mouth disease virus (FMDV)-infected animals from
      vaccinated animals. To address this problem, a new chemiluminescence immunoassay
      (CLIA) method was developed to detect antibodies targeting the two recombinant
      epitope-based proteins located in 3A and 3B. The 3Aepitp-3Bepitp CLIA exhibited a
      diagnostic sensitivity of 94.0% and a diagnostic specificity of 97.5% for the
      detection of serum samples (naive bovines, n = 52, vaccinated bovines, n = 422,
      infected bovines, n = 116) from animals with known status. The CLIA method also
      had a concordance rate of 88.1% with the PrioCHECK FMDV NSP ELISA based on the
      detection of 270 serum samples from the field. Importantly, the 3Aepitp-3Bepitp
      CLIA produced no false-positives when used to detect FMDV in samples from bovines
      that had been vaccinated up to five times, and it was demonstrated a low false
      positive rate when the bovines had been vaccinated up to ten (2.15%) and fifteen
      times (5.93%). Therefore, the 3Aepitp-3Bepitp CLIA detects FMDV in samples from
      frequently vaccinated bovines with high accuracy and represents an alternative
      method to differentiate FMDV-infected and vaccinated bovines.

PMID- 29341486
TI  - Rheumatoid arthritis and periodontal disease: What are the similarities and
      differences?
AB  - Rheumatoid arthritis (RA) and periodontal disease (PD) are chronic inflammatory
      diseases that share similar osteoclasia, human leukocyte antigen-DR4 allelic
      genes and immunological profile, and characteristic cytokines. Smoking can
      contribute to more severe RA and PD; secretion of pro-inflammatory mediators
      destroys the soft synovial membrane and periodontium, respectively. Anti
      citrullinated protein antibodies and anti-alpha-enolase antibody are
      characteristic of these two diseases. Some studies suggest that PD may be
      associated with RA. Anti-Porphyromonas gingivalis (P. gingivalis) antibody, but
      no P. gingivalis bacterium can be detected in RA patients' joint fluid. Anti-P.
      gingivalis antibody has been seen as a biomarker of RA. Both diseases share some
      nosogenesis and common pathological pathways. However, there are differing views
      on the connection between the two diseases. Interferon-inducible-16 (IFI16) is a
      genic marker of RA; moreover, the association between IFI16 and PD is rare. Some
      studies suggest PD is related to periodontal parameters and patient's
      pathological status rather than RA. Disease frequency in men and women differ
      between these two diseases. The expression of interleukin-17 (IL-17) receptor
      only associates with different genders in PD (PD of different sexes have
      different IL-17 expressions). Periodontal local treatment only affects clinical
      periodontal status, and it does not alter circulating levels of IL-6, tumor
      necrosis factor-alpha or C-reactive protein which are associated with RA. This
      review examines the similarities and differences between these two diseases and
      explores possible interactions. Importantly, we will discuss whether PD is a
      feature of RA and whether this knowledge provides helpful information in future
      treatment of both diseases.

PMID- 29341487
TI  - Identification of stress-related microRNA biomarkers in type 2 diabetes mellitus:
      A systematic review and meta-analysis.
AB  - BACKGROUND: Many studies have investigated microRNAs (miRNAs) in the detection of
      type 2 diabetes mellitus (T2DM). Herein, the dysregulated direction of stress
      related miRNAs used as biomarkers of T2DM are summarized and analyzed. METHODS:
      PubMed, EMBASE, ISI Web of Science, and three Chinese databases were searched for
      case-control miRNA profiling studies about T2DM. A meta-analysis under a random
      effect was performed. Subgroup analysis was conducted based on different tissues
      and species. Sensitivity analysis was conducted to confirm the robustness among
      studies. The effect size was pooled using ln odds ratios (ORs), 95% confidence
      intervals (95% CIs), and P-values. RESULTS: The present meta-analysis included 39
      case-control studies with a total of 494 miRNAs. Only 33 miRNAs were reported in
      three or more studies and, of these, 18 were inconsistent in their direction of
      dysregulation. Two significantly dysregulated miRNAs (let-7 g and miR-155) were
      identified in the meta-analysis. Four miRNAs (miR-142-3p, miR-155, miR-21, and
      miR-34c-5p) were dysregulated in patients with T2DM, whereas five miRNAs (miR
      146a, miR-199a-3p, miR-200b, miR-29b and miR-30e) were dysregulated in animal
      models of diabetes. In addition, two dysregulated miRNAs (miR-146a and miR-21)
      were highly cornea specific and heart specific. In sensitivity analysis, only miR
      155 was still significantly dysregulated after removing studies with small sample
      sizes. CONCLUSIONS: The present meta-analysis revealed that 16 stress-related
      miRNAs were significantly dysregulated in T2DM. MiR-148b, miR-223, miR-130a, miR
      19a, miR-26b and miR-27b were selected as potential circulating biomarkers of
      T2DM. In addition, miR-146a and miR-21 were identified as potential tissue
      biomarkers of T2DM.

PMID- 29341488
TI  - Gene-gene interaction between MSX1 and TP63 in Asian case-parent trios with
      nonsyndromic cleft lip with or without cleft palate.
AB  - BACKGROUND: Small ubiquitin-like modification, also known as sumoylation, is a
      crucial post-translational regulatory mechanisms involved in development of the
      lip and palate. Recent studies reported two sumoylation target genes, MSX1 and
      TP63, to have achieved genome-wide level significance in tests of association
      with nonsyndromic clefts. Here, we performed a candidate gene analysis
      considering gene-gene and gene-environment interaction for SUMO1, MSX1, and TP63
      to further explore the etiology of nonsyndromic cleft lip with or without cleft
      palate (NSCL/P). METHODS: A total of 130 single-nucleotide polymorphisms (SNPs)
      in or near SUMO1, MSX1, and TP63 was analyzed among 1,038 Asian NSCL/P trios
      ascertained through an international consortium. Conditional logistic regression
      models were used to explore gene-gene (G * G) and gene-environment (G * E)
      interaction involving maternal environmental tobacco smoke and multivitamin
      supplementation. Bonferroni correction was used for G * E analysis and
      permutation tests were used for G * G analysis. RESULTS: While transmission
      disequilibrium tests and gene-environment interaction analysis showed no
      significant results, we did find signals of gene-gene interaction between SNPs
      near MSX1 and TP63. Three pairwise interactions yielded significant p values in
      permutation tests (rs884690 and rs9290890 with p = 9.34 * 10-5 and empirical p =
      1.00 * 10-4 , rs1022136 and rs4687098 with p = 2.41 * 10-4 and empirical p = 2.95
      * 10-4 , rs6819546 and rs9681004 with p = 5.15 * 10-4 and empirical p = 3.02 * 10
      4 ). CONCLUSION: Gene-gene interaction between MSX1 and TP63 may influence the
      risk of NSCL/P in Asian populations. Our study provided additional understanding
      of the genetic etiology of NSCL/P and underlined the importance of considering
      gene-gene interaction in the etiology of this common craniofacial malformation.

PMID- 29341489
TI  - Palladium-Catalyzed Atom-Transfer Radical Cyclization at Remote Unactivated C(sp3
      )-H Sites: Hydrogen-Atom Transfer of Hybrid Vinyl Palladium Radical
      Intermediates.
AB  - A novel mild, visible-light-induced palladium-catalyzed hydrogen atom
      translocation/atom-transfer radical cyclization (HAT/ATRC) cascade has been
      developed. This protocol involves a 1,5-HAT process of previously unknown hybrid
      vinyl palladium radical intermediates, thus leading to iodomethyl carbo- and
      heterocyclic structures.

PMID- 29341490
TI  - Containing influenza outbreaks with antiviral use in long-term care facilities in
      Taiwan, 2008-2014.
AB  - BACKGROUNDS: Influenza can spread rapidly in long-term care facilities (LTCFs),
      and residents are usually at higher risk for influenza infections. OBJECTIVE: Our
      study aimed to evaluate the effectiveness of antiviral interventions on outbreak
      control. METHODS: Taiwan Centers for Disease Control used a syndromic
      surveillance system to monitor outbreaks in LTCFs. Local public health
      authorities verified those outbreaks and logged reports to the Epidemic
      Investigation Report Files Management System (EIRFMS). We conducted a
      retrospective cohort study by reviewing EIRFMS reports of influenza outbreaks in
      LTCFs during 2008-2014. An influenza outbreak was defined as 3 or more cases of
      influenza-like illness occurring within a 48-hours period with >=1 case of real
      time RT-PCR-confirmed influenza in the same LTCF. Antiviral interventions
      included providing antiviral treatment for patients and antiviral prophylaxis for
      contacts during outbreaks. RESULTS: Of 102 influenza outbreaks, median days from
      onset of the first patient to outbreak notification was 4 (range 0-22). Median
      attack rate was 24% (range 2.2%-100%). Median influenza vaccination coverage
      among residents was 81% (range 0%-100%); 43% occurred during the summer months.
      Even though antiviral treatment was provided in 87% of the outbreaks, antiviral
      prophylaxis was implemented in only 40%. Starting antiviral treatment within 2
      days of outbreak onset was associated with keeping attack rates at <25% (OR 0.29,
      95% CI: 0.12-0.71). CONCLUSIONS: Early initiation of antiviral treatment may
      reduce the magnitude of influenza outbreaks. Clinicians should identify patients
      with influenza and start antiviral use early to prevent large outbreaks in LTCFs.

PMID- 29341492
TI  - Winner of the society for biomaterials student award in the Ph.D. category for
      the annual meeting of the society for biomaterials, april 11-14, 2018, Atlanta,
      GA: Development of a bimodal, in situ crosslinking method to achieve multifactor
      release from electrospun gelatin.
AB  - To better mimic native tissue microenvironments, current efforts have moved
      beyond single growth factor delivery to more complex multiple growth factor
      delivery with distinct release profiles. Electrospun gelatin, a widely
      investigated drug delivery vehicle, requires postprocessing crosslinking
      techniques that generate a mesh with uniform crosslinking density, limiting the
      ability to deliver multiple factors at different rates. Herein, we describe a
      method to independently control release of multiple factors from a single
      electrospun gelatin mesh. Two in situ crosslinking modalities, photocrosslinking
      of methacyrlated gelatin and reactive crosslinking of gelatin with a
      diisocyanate, are coelectrospun to generate distinct fiber populations with
      different crosslinking chemistry and density in a single mesh. The
      photocrosslinked gelatin-methacrylate resulted in a relatively rapid release of a
      model protein (48 +/- 12% at day 1, 96 +/- 3% at day 10) due to diffusion of
      embedded protein from the crosslinked fibers. The reactive crosslinking system
      displayed a more sustained release (7 +/- 5% at day 1, 33 +/- 2% at day 10) that
      was attributed to the conjugation of protein to gelatin with the diisocyanate,
      requiring degradation of gelatin prior to diffusion out of the fibers. Both
      modalities displayed tunable release profiles. Subsequent release studies of a
      cospun mesh with two different crosslinked fiber populations confirmed that the
      cospun mesh displayed multifactor release with independent release profiles.
      Overall, this bimodal, in situ crosslinking approach enables the delivery of
      multiple factors with distinct release kinetics from a single mesh and is
      expected to have broad utility in tissue engineering. (c) 2018 Wiley Periodicals,
      Inc. J Biomed Mater Res Part A: 106A: 1155-1164, 2018.

PMID- 29341491
TI  - Clinical outcomes of carbon ion radiotherapy with concurrent chemotherapy for
      locally advanced uterine cervical adenocarcinoma in a phase 1/2 clinical trial
      (Protocol 1001).
AB  - We conducted a phase 1/2 study to evaluate the efficacy and safety of carbon ion
      radiotherapy (C-ion RT) with concurrent chemotherapy for locally advanced uterine
      cervical adenocarcinoma. Thirty-three patients were enrolled between April 2010
      and March 2014. Treatment consisted of C-ion RT with concurrent weekly cisplatin
      at a dose of 40 mg/m2 . In the phase 1 component, the total dose was escalated
      from 68.0 Gy (relative biological effectiveness [RBE]) to 74.4 Gy (RBE) to
      determine the maximum tolerated dose of C-ion RT. In the phase 2 component, the
      efficacy and safety of C-ion RT with concurrent chemotherapy were evaluated using
      the dose determined in the phase 1 component. The median follow-up duration was
      30 months. Two patients did not receive chemotherapy because of anemia or
      leukocytopenia immediately prior to commencing treatment; 31 patients were
      analyzed. None of the patients developed dose-limiting toxicities. The
      recommended dose (RD) was determined to be 74.4 Gy (RBE). In the phase 2
      component, two patients developed Grade 3-4 toxicities in the gastrointestinal
      tract, due to repeated laser coagulation or peritonitis caused by appendicitis.
      In the patients treated with the RD, the 2-year local control, progression-free
      survival, and overall survival rates were 71%, 56%, and 88%, respectively. C-ion
      RT with concurrent weekly cisplatin was well tolerated in patients with locally
      advanced uterine cervical adenocarcinoma. Our findings support further
      investigations into the efficacy of this strategy.

PMID- 29341493
TI  - Modeling the Downstream Processing of Monoclonal Antibodies Reveals Cost
      Advantages for Continuous Methods for a Broad Range of Manufacturing Scales.
AB  - The biopharmaceutical industry is evolving in response to changing market
      conditions, including increasing competition and growing pressures to reduce
      costs. Single-use (SU) technologies and continuous bioprocessing have attracted
      attention as potential facilitators of cost-optimized manufacturing for
      monoclonal antibodies. While disposable bioprocessing has been adopted at many
      scales of manufacturing, continuous bioprocessing has yet to reach the same level
      of implementation. In this study, the cost of goods of Pall Life Science's
      integrated, continuous bioprocessing (ICB) platform is modeled, along with that
      of purification processes in stainless-steel and SU batch formats. All three
      models include costs associated with downstream processing only. Evaluation of
      the models across a broad range of clinical and commercial scenarios reveal that
      the cost savings gained by switching from stainless-steel to SU batch processing
      are often amplified by continuous operation. The continuous platform exhibits the
      lowest cost of goods across 78% of all scenarios modeled here, with the SU batch
      process having the lowest costs in the rest of the cases. The relative savings
      demonstrated by the continuous process are greatest at the highest feed titers
      and volumes. These findings indicate that existing and imminent continuous
      technologies and equipment can become key enablers for more cost effective
      manufacturing of biopharmaceuticals.

PMID- 29341494
TI  - The importance of biomarkers of fetal exposure to alcohol and psychotropic drugs
      in early diagnosis: A case report.

PMID- 29341495
TI  - Validation of a fully automated solid-phase extraction and ultra-high-performance
      liquid chromatography-tandem mass spectrometry method for quantification of 30
      pharmaceuticals and metabolites in post-mortem blood and brain samples.
AB  - In this study, we present the validation of an analytical method capable of
      quantifying 30 commonly encountered pharmaceuticals and metabolites in whole
      blood and brain tissue from forensic cases. Solid-phase extraction was performed
      by a fully automated robotic system, thereby minimising manual labour and human
      error while increasing sample throughput, robustness, and traceability. The
      method was validated in blood in terms of selectivity, linear range, matrix
      effect, extraction recovery, process efficiency, carry-over, stability,
      precision, and accuracy. Deuterated analogues of each analyte were used as
      internal standards, which corrected adequately for any inter-individual
      variability in matrix effects on analyte accuracy and precision. The lower limit
      of quantification (LLOQ) spanned from 0.0008 to 0.010 mg/kg, depending on the
      analyte, while the upper LOQ ranged between 0.40 and 2.0 mg/kg. Thus, the linear
      range covered both therapeutic and toxic levels. The method showed acceptable
      accuracy and precision, with accuracies ranging from 80 to 118% and precision
      below 19% for the majority of the analytes. Linear range, matrix effect,
      extraction recovery, process efficiency, precision, and accuracy were also tested
      in brain homogenate and the results agreed with those from blood. An additional
      finding was that the analyte concentrations in brain samples could be quantified
      by calibration curves obtained from spiked blood samples with acceptable
      precision and accuracy when using deuterated analogues of each analyte as
      internal standards. This method has been successfully implemented as a routine
      analysis procedure for quantification of pharmaceuticals in both blood and brain
      tissue since 2015.

PMID- 29341496
TI  - Association of genetic variants in the interleukin-18 gene promoter with risk of
      hepatocellular carcinoma and metastasis in patients with hepatitis C virus
      infection.
AB  - Hepatocellular carcinoma (HCC) is a primary malignancy of the liver,
      characterized by high vascularization and rapid tumor progression. The current
      case-control study aimed to analyze the influence of -607C/A and -137G/C
      polymorphisms in the interleukin-18 (IL-18) promoter on the risk of HCC
      occurrence and metastasis in Egyptian patients infected with hepatitis C virus
      (HCV). Both genetic variations were genotyped in 279 subjects including HCV
      patients with and without HCC and unrelated healthy subjects, using the allele
      specific polymerase chain reaction (AS-PCR) method. The relationship between
      clinico-laboratory parameters including serum level of alpha-fetoprotein (AFP)
      and these polymorphisms was evaluated in HCC patients. The IL-18-607A allele and
      AA genotype were significantly related to a higher risk of developing HCC when
      comparing patients with HCC and controls, and were significantly related to a
      higher risk of metastasis when comparing metastatic and nonmetastatic groups in
      the Egyptian patients. In contrast, the IL18-137C allele and GC genotype were
      significantly related to a lower risk of developing HCC when comparing patients
      with HCC and controls, and HCV patients with and without HCC. A significant
      association was found between multinodular HCC and IL-18-607AA genotype, while,
      uninodular HCC was significantly associated with IL-18-137GG genotype. In
      addition, IL18-607AA and -137GG genotypes showed significant association with
      higher level of serum AFP. The detection of polymorphisms in the IL-18 promoter,
      in a combination with an evaluation of level of serum AFP, could be used as a
      molecular biomarker in the early diagnosis of HCC, which would aid the early
      management of the disease, thus decreasing the rate of mortality of this disease.
      (c) 2018 IUBMB Life, 70(2):165-174, 2018.

PMID- 29341497
TI  - Defining behavioral components of social functioning in adults with autism
      spectrum disorder as targets for treatment.
AB  - : There is increasing recognition that adults with autism spectrum disorder (ASD)
      would benefit from treatment to improve social functioning, a key factor in
      adults' overall quality of life. However, the various behavioral components of
      social functioning (i.e., categories of behaviors underlying social functioning),
      including social motivation, social anxiety, social cognition, and social skills,
      have not all been assessed together in any sample of adults with ASD, making it
      difficult to know the relative levels of impairment in these various categories,
      the relationships among these categories, or promising targets for treatments. We
      hypothesized there would be significant correlations among measures within the
      same category, but fewer correlations of measures between categories, indicating
      the heterogeneity of impairments in adults with ASD. Twenty-nine adults with ASD
      without co-occurring intellectual disability completed multiple assessments
      measuring social motivation, social anxiety, social cognition, and social skills,
      as well as measures of overall ASD symptom levels and community functioning.
      Results revealed significant positive correlations among measures within most
      categories; positive correlations between measures of social motivation and all
      other categories, except for social cognition; as well as positive cross-domain
      correlations between measures of anxiety and ASD phenotype; measures of social
      skills and community functioning; and measures of social skills and ASD
      phenotype. Further studies are warranted to determine causal relationships among
      these behavioral categories, across developmental stages. However, the lack of
      correlations between many categories suggests the potential importance of
      multidimensional treatments that target the particular components of social
      functioning most in need of improvement in individuals. Autism Res 2018, 11: 488
      502. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc.
      LAY SUMMARY: The goal of this study was to measure behaviors that contribute to
      social functioning difficulties in adults with ASD, with the ultimate goal of
      guiding treatment development. We found that motivation to interact with others
      was significantly related to social anxiety and social skill. Our results suggest
      that motivation may be important to target in treatment, and that treatments
      should be tailored to the areas most in need of improvement in each individual.

PMID- 29341498
TI  - Review article: Sepsis in the emergency department - Part 2: Investigations and
      monitoring.
AB  - Sepsis is characterised by organ dysfunction resulting from infection, with no
      reliable single objective test and current diagnosis based on clinical features
      and results of investigations. In the ED, investigations may be conducted to
      diagnose infection as the cause of the presenting illness, identify the source,
      distinguish sepsis from uncomplicated infection (i.e. without organ dysfunction)
      and/ or risk stratification. Appropriate sample collection for microbiological
      testing remains key for subsequent confirmation of diagnosis and rationalisation
      of antimicrobials. Routine laboratory investigations such as creatinine,
      bilirubin, platelet count and lactate are now critical elements in the diagnosis
      of sepsis and septic shock. With no biomarker sufficiently validated to rule out
      bacterial infection in the ED, there remains substantial interest in biomarkers
      representing various pathogenic pathways. New technologies for screening multiple
      genes and proteins are identifying unique network 'signatures' of clinical
      interest. Other future directions include rapid detection of bacterial DNA in
      blood, genes for antibiotic resistance and EMR-based computational biomarkers
      that collate multiple information sources. Reliable, cost-effective tests,
      validated in the ED to promptly and accurately identify sepsis, and to guide
      initial antibiotic choices, are important goals of current research efforts.

PMID- 29341499
TI  - Recommendations on diagnostic tools for Batrachochytrium salamandrivorans.
AB  - Batrachochytrium salamandrivorans (Bsal) poses a major threat to amphibian, and
      more specifically caudata, diversity. Bsal is currently spreading through Europe,
      and mitigation measures aimed at stopping its spread and preventing its
      introduction into naive environments are urgently needed. Screening for presence
      of Bsal and diagnosis of Bsal-induced disease in amphibians are essential core
      components of effective mitigation plans. Therefore, the aim of this study was to
      present an overview of all Bsal diagnostic tools together with their limitations
      and to suggest guidelines to allow uniform interpretation. Here, we investigate
      the use of different diagnostic tools in post-mortem detection of Bsal and
      whether competition between Bd and Bsal occurs in the species-specific Bd and
      Bsal duplex real-time PCR. We also investigate the diagnostic sensitivity,
      diagnostic specificity and reproducibility of the Bsal real-time PCR and show the
      use of immunohistochemistry in diagnosis of Bsal-induced chytridiomycosis in
      amphibian samples stored in formaldehyde. Additionally, we have drawn up
      guidelines for the use and interpretation of the different diagnostic tools for
      Bsal currently available, to facilitate standardization of execution and
      interpretation.

PMID- 29341500
TI  - Investigation of the free heavy chain homodimers of a monoclonal antibody.
AB  - Monoclonal antibodies (mAbs) are composed of two heavy chain (HC) and two light
      chain (LC) polypeptides. The proper folding and assembly of HC and LC is critical
      for antibody production. Current dogma indicates that the free HCs are retained
      in the endoplasmic reticulum (ER) unless assembled with LCs into antibodies,
      while the LCs on the other hand can be secreted as free monomer or dimer
      molecules. In this study, high levels of extracellular HC homodimers (7%-45%)
      were observed in the cell culture media during cell line development for mAb1.
      Excellent correlation (R2  > 0.9) between the level of free HC homodimers and the
      percentage of high molecular weight species indicates that the free HC homodimers
      might be causative of unwanted aggregation. Due to the different surface charge
      of HC homodimer and fully assembled antibodies, the unwanted extracellular HC
      homodimers were successfully removed by downstream processing, through a cation
      exchange chromatography step. Reduced capillary electrophoresis-sodium dodecyl
      sulfate (rCE-SDS) analysis of the cell culture media from different MTX-amplified
      pools indicated that insufficient expression of LC is one potential root cause
      for the high level of free HC homodimers. The level of free HC homodimers
      decreased significantly (3%-25%) after retransfecting the MTX amplified pools
      with additional LC gene. (c) 2018 American Institute of Chemical Engineers
      Biotechnol. Prog., 34:738-745, 2018.

PMID- 29341501
TI  - Tadalafil Improves Symptoms, Erectile Function and Quality of Life in Patients
      with Lower Urinary Tract Symptoms Suggestive of Benign Prostatic Hyperplasia (KYU
      PRO Study).
AB  - OBJECTIVES: Effect of tadalafil on lower urinary tract symptoms (LUTS), erectile
      function and quality of life (QoL) were prospectively evaluated in patients with
      benign prostatic hyperplasia (BPH) at multicenter. METHODS: Eligible men were
      >=40 years who had no treatment with alpha-blocker for BPH, with total
      International Prostate Symptom Score (IPSS) >=8, IPSS-QOL >=2 and prostate volume
      >=20 mL. Data were collected on age, body mass index (BMI), and prostate specific
      antigen (PSA). Patients were asked to complete a self-reported questionnaire
      regarding the IPSS, Overactive Bladder Symptom Score (OABSS), International Index
      of Erectile Function 5 (IIEF5), and Medical Outcome Study 8-Item Short-Form
      Health Survey (SF-8). These measures were assessed at baseline, 4-, 8-, 12-week
      of tadalafil treatment. In addition, uroflowmetry was also performed at baseline,
      and 12-week end point visit. RESULTS: Thirty five patients with mean age 67.3
      years, mean BMI 23.6 kg/m2 , mean prostate volume 36 mL, and mean PSA 3.4 ng/mL
      were enrolled. Treatment with tadalafil significantly improved IPSS total score,
      IPSS voiding subscore, IPSS storage subscore, OABSS and IPSS-QoL score after 4
      weeks and these improvements were maintained for 12-week treatment period. IIEF5
      score and general health in SF-8 are significantly improved with the treatment of
      tadalafil. However, maximum flow rate and postvoiding residual volume were not
      significantly changed. There were not any serious adverse events. CONCLUSIONS:
      These results indicate that tadalafil 5 mg once daily would be effective and well
      tolerated treatment in Japanese men with BPH-LUTS.

PMID- 29341502
TI  - Advances in intravesical therapy for bladder pain syndrome (BPS)/interstitial
      cystitis (IC).
AB  - Bladder pain syndrome (BPS)/interstitial cystitis (IC) is a chronic symptom
      complex that may cause bothersome storage symptoms and pain or discomfort of the
      bladder, adversely affecting a patient's quality of life. The etiology of IC/BPS
      remains unclear, and its cause may be multifactorial. Diagnosis of IC/BPS is
      based on clinical features, and the possibility of other conditions must be ruled
      out first. Although no definitive treatment is currently available for IC/BPS,
      various intravesical therapies are used for IC/BPS, including heparin, hyaluronic
      acid, chondroitin sulfate, pentosan polysulfate, dimethylsulfoxide, liposomes,
      and botulinum onabotulinumtoxinA (BoNT-A). This review summarizes the
      intravesical therapy for IC/BPS and discusses recent advances in the instillation
      of liposomal-mediated BoNT-A and other newly developed intravesical therapies.

PMID- 29341503
TI  - Tadalafil 5 mg Once Daily Improves Lower Urinary Tract Symptoms and Erectile
      Dysfunction: A Systematic Review and Meta-analysis.
AB  - OBJECTIVES: We carried out a systematic review and meta-analysis to assess
      tadalafil 5 mg once-daily for the treatment of lower urinary tract symptoms
      (LUTS) and erectile dysfunction (ED). METHODS: A literature review was performed
      to identify all published randomized double-blind, placebo-controlled trials of
      tadalafil 5 mg once-daily for the treatment of LUTS and ED. The search included
      the following databases: MEDLINE, EMBASE, and the Cochrane Controlled Trials
      Register. The reference lists of the retrieved studies were also investigated.
      RESULTS: Thirteen publications involving a total of 3973 patients were used in
      the analysis, including 13 RCTs that compared tadalafil 5 mg once-daily with
      placebo. We found that tadalafil 5 mg once-daily was effective in improving LUTS
      suggestive of BPH and treating ED over 12 weeks in our meta-analysis. Total
      International Prostate Symptom Score (IPSS) (SMD = - 2.02, 95% CI = - 2.52 to 
      1.53, P < 0.00001); Benign Prostatic Hyperplasia Impact Index (BPH-II) (SMD = 
      0.58, 95% CI = -0.84 to -0.33, P < 0.00001); International Index of Erectile
      Function-erectile function (IIEF) domain (standardized mean difference [SMD] =
      5.18, 95% confidence interval [CI] = 4.13-6.23, P < 0.00001) indicated that
      tadalafil 5 mg once-daily was more effective than the placebo. Safety assessments
      included discontinuations due to adverse event (odds ratio (OR) = 1.79, 95% CI =
      1.12-2.85, P = 0.01) indicated that tadalafil 5 mg once-daily was well tolerated.
      CONCLUSIONS: This meta-analysis indicates that tadalafil 5 mg once-daily to be an
      effective treatment for LUTS and ED with a low occurrence of side effects.

PMID- 29341504
TI  - A multi-institutional analysis of children on long-term non-invasive respiratory
      support and their outcomes.
AB  - OBJECTIVES: To characterize a multi-institutional cohort of children with chronic
      respiratory failure that use long-term, non-invasive respiratory support, perform
      a time-to-event analysis of transitions to transtracheal ventilation and identify
      factors associated with earlier transition to transtracheal ventilation. STUDY
      DESIGN: A retrospective cohort study of patients less than 21 years of age with
      diagnoses associated with chronic respiratory failure and discharged on non
      invasive respiratory support was performed using data from the Pediatric Health
      Information System (PHIS) between 2007 and 2015. Demographic and clinical
      characteristics, as well as times from index discharge on non-invasive support to
      transtracheal ventilation were presented. A competing risk regression model was
      fitted to estimate factors associated with earlier transition to transtracheal
      ventilation. RESULTS: A total of 3802 patients were identified. Their median age
      at index discharge was 10.4 years (interquartile range [IQR] 4.1-14.9). Of these
      patients, 337 (8.9%) transitioned to transtracheal ventilation and transitioned
      at a median of 11.5 months (IQR 4.6-26) post-index discharge, or a median age of
      9.3 years (IQR 4.2-14.5). Competing risk modeling demonstrated that patients who
      were older or whose discharge occurred later in the study period had lower
      hazards of earlier transition to transtracheal ventilation, whereas patients with
      anoxia/encephalopathy and quadriplegia had higher hazards of earlier
      transitioning. CONCLUSIONS: Most patients on long-term, non-invasive respiratory
      support who progress to transtracheal ventilation transition do so within a few
      years of support initiation. Various characteristics were associated with earlier
      risk of transitioning to transtracheal ventilation. This information may enhance
      anticipatory guidance for this population.

PMID- 29341505
TI  - Stability, integrity, and recovery rate of cellular nucleic acids preserved in a
      new liquid-based cytology medium.
AB  - BACKGROUND: Liquid-based cytology (LBC) has replaced the conventional
      Papanicolaou test in cervical cancer screening. The cervical swab specimens
      collected in LBC media can also be used for additional analyses including high
      risk HPV (HR-HPV) test, DNA methylation analysis, and HPV E6/E7 mRNA test.
      METHODS: The stability, integrity, and recovery rate of cellular DNA and RNA
      after storage at different conditions were evaluated by a quantitative real-time
      PCR (qPCR) based HR-HPV test, reverse transcription qPCR (RT-qPCR), and agarose
      gel electrophoresis. Cervical swab specimens collected in a newly developed LBC
      medium, VersaMedium, and ThinPrep PreservCyt medium were processed on Hologic
      ThinPrep 5000 instrument. RESULTS: Cervical exfoliative cells fixed by
      VersaMedium exhibited good cellular morphology with intact membranes and
      delineated chromatin structures. Cellular DNA preserved in VersaMedium exhibited
      high level of stability at both room temperature and 4 degrees C, and remained
      mostly intact at 4 degrees C for up to 28 days. Cellular RNA preserved in
      VersaMedium maintained higher level of stability and integrity at 4 degrees C
      than at room temperature. VersaMedium also showed no apparent adverse effect on
      the recovery rate of nucleic acids. CONCLUSION: In addition to maintaining
      cellular morphology, when stored at 4 degrees C, VersaMedium preserves cellular
      nucleic acids and PreservCyt medium without noticeable adverse effects on the
      recovery rate during purification. Therefore, VersaMedium is an appropriate LBC
      medium for the collection and preservation of cervical swab specimens. And
      VersaMedium preserved cellular nucleic acids are of such high quality that they
      are suitable for HR-HPV qPCR test and RT-qPCR analyses.

PMID- 29341507
TI  - Residents Rosters: Reversal to Longer Hours in the US.

PMID- 29341508
TI  - Delirium and the acute hospital system of the Republic of Ireland: Challenges,
      solutions and opportunities.

PMID- 29341506
TI  - Impact of preoperative anemia on outcomes in patients undergoing curative
      resection for gastric cancer: a single-institution retrospective analysis of 2163
      Chinese patients.
AB  - We sought to evaluate whether preoperative anemia was an important determinant of
      survival in gastric cancer (GC). A single institution cohort of 2163 GC patients
      who underwent curative resection were retrospectively analyzed. Anemia was
      defined as a preoperative hemoglobin level <120 g/L in males and <110 g/L in
      females. Overall survival (OS) was analyzed using the Kaplan-Meier method, and a
      multivariate Cox proportional hazards model was performed to identify the
      independent prognostic factor. Anemic patients had a poorer OS compared with
      nonanemic patients after resection for tumor-nodes-metastasis (TNM) stage III
      tumors (5-year OS rate: 32.2% vs. 45.7%, P < 0.001) but not stage I (P  =  0.480)
      or stage II (P  =  0.917) tumors. Multivariate analysis revealed that
      preoperative anemia was an independent prognostic factor in TNM stage III (hazard
      ratio [HR], 1.771; 95% CI, 1.040-3.015; P = 0.035). In a stage-stratified
      analysis, preoperative anemia was still independently associated with OS in TNM
      stages IIIa through IIIc (P < 0.001, P = 0.075, and P = 0.012, respectively),
      though the association was only marginal in stage IIIb. Of note, preoperative
      mild anemia had a similar prognostic value in TNM stage III GC. Furthermore,
      preoperative anemia was significantly associated with more perioperative
      transfusions, postoperative complications and several nutritional-based indices,
      including the prognostic nutritional index (PNI), preoperative weight loss and
      performance status (all P < 0.05). Preoperative anemia, even mild anemia, was an
      important predictor of postoperative survival for TNM stage III GC.

PMID- 29341509
TI  - Effect of the 2008 economic crisis on the cardiovascular mortality of the Irish
      population: an ecological 12-year study of a heart-broken Celtic Tiger.
AB  - Ireland has endured a substantial financial crisis in 2008 and we sought to
      explore the effect of economic recession on Irish cardiovascular mortality. We
      found an increase by 17.2% in CVA-deaths during the financial crisis years (95%
      CI 11.1% to 23.6%). In males, we found a notable rise in the annual IHD rate by
      7.56% (95% CI 4.73% to 10.46%), in annual MI rate by 2.96% (95% CI 0.16% to
      5.84%), and in annual CVA death rate by 20.07% (95% CI 16.13% to 24.14%). In
      females our findings indicated an increased rate of CVA-related deaths during the
      economic crisis by 15.54% (95% CI 6.67% to 25.16%). Irish CVA-related deaths
      increased during the economic crisis for males and females alike. Male IHD
      related deaths have also risen indicating a potential differential effect for
      financial hardships on male gender mortality.

PMID- 29341510
TI  - Maternity Ultrasound in the Republic of Ireland 2016; A Review.
AB  - Antenatal ultrasound, comprising of a dating ultrasound in the late first
      trimester followed by a fetal anomaly scan, is a recognised and necessary
      component of good antenatal care. We conducted a telephone survey of all 19
      obstetric units to ascertain the status of maternity ultrasound provision in
      Ireland. Fetal anomaly ultrasound is offered universally to all women in 7/19
      (37%) units, selectively to some women in 7/19 (37%) units and not offered at all
      in the remaining 5/19 (26%) units. Overall ? 41,700 (64%) women receive a fetal
      anomaly ultrasound nationally. Universal first trimester ultrasound, performed in
      a dedicated ultrasound department by a suitably qualified sonographer, is offered
      to 47% of women nationally. This study highlights the lack of development in
      Irish maternity ultrasound services over the last decade. Substantial investment
      by health care policy makers is urgently needed.

PMID- 29341511
TI  - Age Adjusted D-Dimer for exclusion of Pulmonary Embolism: a retrospective cohort
      study.
AB  - D-Dimer (DD) will increase with age and recent studies have shown the upper limit
      of normal can be raised in those who are low risk and over 50. We studied age
      adjusted D-dimer (AADD) levels to assess whether pulmonary embolism (PE) could be
      safely excluded. This study analysed the Emergency Department (ED) Computed
      Tomographic Pulmonary Angiography (CTPA) requests. There were 756 requests. The
      parameters studied were; age, DD value, calculated AADD, CT result and Simplified
      Geneva Score (SGS). The primary outcome was the diagnostic performance of AADD.
      One hundred and eighty-five patients were included in the final cohort. Twenty
      one patients had a negative DD after age adjustment. Of these one had a PE,
      corresponding to a failure rate of 4.76% (1 in 22). The sensitivity of AADD was
      0.96 (95% CI 0.76 to 0.99) and its specificity was 0.12 (95% CI 0.08- 0.19). AADD
      demonstrated a reduction in false positives with one false negative, giving rise
      to a failure rate higher than that of other larger studies. Further study is
      indicated to accurately define the diagnostic characteristics for the Irish
      context.

PMID- 29341512
TI  - Food Allergy Emergencies in Children - To what extent are Early Years Services
      Prepared? A cross-sectional survey.
AB  - Food allergies are common in preschool children. This study's aims are to
      establish prevalence, to clarify management practices, levels of preparedness and
      the perceived role of General Practitioners amongst Early Years Services
      providers. This study is an anonymous, quantitative, cross sectional study. An
      online questionnaire was distributed to 282 Early Years Service providers. Data
      were analysed using SPSS. Response rate was 35% (n=98). Prevalence of food
      allergy was 3% (n=119). Allergic reactions to food had occurred on site in 16%
      (n=15). Written emergency action plans were available in 47% of facilities
      (n=46). Medications were not kept on site in 63% (n=62) of facilities. General
      practitioners were felt to have an important role in the management of food
      allergies by 76% of respondents (n=61). This study identifies significant areas
      for improvement in the management of food allergic child in Early Years Services.

PMID- 29341513
TI  - Investment in epilepsy monitoring units improves epilepsy care-experience in a
      regional neuroscience centre.
AB  - An evaluation of the clinical yield of inpatient long-term video-EEG (vEEG) in a
      new epilepsy monitoring unit (EMU) was undertaken, with findings compared to the
      centre's prior method of bedside vEEG recording in a standard neurology ward, as
      reported in 2004. A retrospective analysis of neurophysiology reports for all
      adults who underwent elective vEEG monitoring in the EMU at Cork University
      Hospital between January 2015 and July 2016 was conducted. Of 115 vEEG studies in
      the EMU, 100 (87.0%) were deemed diagnostically conclusive, 14 (12.2%) failed to
      catch any clinical events and showed normal EEG throughout, and one (0.9%)
      captured spells of unclear clinical significance - the corresponding figures
      reported in 2004 for bedside vEEGs were 21.3%, 77% and 1.6%, respectively. The
      EMU offers a more effective method of recording inpatient vEEG, which aids
      decision-making and improves clinical outcomes. Some evidence-based measures
      which could further enhance diagnostic yield are discussed.

PMID- 29341514
TI  - Opportunity Costs in Paediatric Training: The Specialist Registrars Experience.
AB  - In the training process, there is a tension between the work life and home life
      of trainees. This study explored both the personal impact and the opportunity
      costs of training from the Specialist Paediatric Registrar (SPR) perspective. The
      survey explored 1) career progression, 2) perceived functional effectiveness at
      work, 3) psychological impact of hospital based training, and 4) the personal and
      social cost of training. Fifty-three (71%) SPRs responded of whom 47 (89%)were
      married or in long term relationships. Seventy-five percent of trainees had a
      definite career plan with 86% intending to undertake fellowship training. Seventy
      percent believed they were efficient time managers but 53% had difficulty in
      making time for academic pursuits and fifty percent experienced negative
      feelings, which lingered after work and interfered with their relationships at
      home. Seventy-four percent stated training was undertaken at significant personal
      cost with only 21% achieving a very satisfactory work/life balance. To address
      these difficulties trainee wellbeing should be addressed at the Basic Specialist
      Training (BST) level and the career path clearly explained outlining the
      challenges that are likely to be encountered.

PMID- 29341515
TI  - The Uptake of Human Papillomavirus Vaccine In Irish Schools: The Impact Of
      Disadvantage.
AB  - HPV vaccine Gardasil(c) is offered to girls in first year of secondary school in
      Ireland. We aimed to determine the association between HPV vaccine uptake among
      girls for academic year 2013/2014, by school and school characteristics:
      socioeconomic disadvantage and religious ethos. The National Schools Immunisation
      System (SIS) was searched to determine HPV vaccine uptake in schools for
      2013/2014 (prior to recent anti-HPV vaccine publicity). The disadvantaged status
      and ethos of each school was added to the report. In total 577 schools were
      identified. Mean vaccine uptake was 83.7%. Disadvantaged schools had a lower mean
      uptake (%) than other schools (79.4% vs 85.0%, difference 5.58%, 95%CI 2.69-8.21)
      and were twice as likely to have an uptake of ?50% (OR 2.07, 95% CI 2.76 - 5.18).
      No difference was found between schools of different ethoses. HPV vaccine uptake
      is lower in disadvantaged Irish schools. Policies should be developed to ensure a
      more equitable uptake of HPV vaccine.

PMID- 29341516
TI  - Epithelioid Angiomyolipoma - a case report and review of the literature.
AB  - Herein we present the case of a 43-year-old female in whom a left renal mass was
      identified incidentally on imaging performed for staging of a newly diagnosed
      breast carcinoma. The mass was resected and histologic examination and
      immunohistochemistry confirmed a diagnosis of epithelioid angiomyolipoma.

PMID- 29341517
TI  - Proliferative myositis of the latissimus dorsi presenting in a 20-year-old male
      athlete.
AB  - We describe the case of a 20-year-old rower presenting with an uncommon condition
      of Proliferative Myositis (PM) affecting the Latissimus Dorsi (LD). PM is a rare,
      benign tumour infrequently developing in the upper back. Its rapid growth and
      firm consistency may mistake it for sarcoma at presentation. Therefore, careful
      multidisciplinary work-up is crucial, and should involve appropriate radiological
      and histopathological investigations. Here, we propose the aetiology of LD PM to
      be persistent myotrauma induced by repetitive rowing motions. Symptoms and rate
      of progression ultimately determine the management which includes surveillance
      and/or conservative resection. There have been no documented cases of recurrence
      or malignant transformation.

PMID- 29341518
TI  - Harlequin Ichthyosis - A Case Report.
AB  - Harlequin Ichthyosis is a very rare genetic disorder affecting mainly the skin
      with severe morbidity and mortality. It affects both sexes with incidence of
      about 1 in 300,000 live births. Autosomal recessive inheritance has been inferred
      with mutation in ABCA 12 gene identified. Hence, genetic counseling and mutation
      screening of this gene should be considered in at-risk patients. Death usually
      occurred in the first 3 months of life due to sepsis, feeding problems and
      respiratory distress. With improved neonatal care and early introduction of
      retinoids, its survival rate has increased.

PMID- 29341519
TI  - Pelvic and acetabular trauma care in Ireland: the past, present and future.

PMID- 29341520
TI  - Reclassification of Category 1-Caesarean Section.

PMID- 29341521
TI  - 2015-2016 Influenza Season in an Irish Regional Paediatric Unit: Importance of
      Influenza Vaccination Highlighted.

PMID- 29341522
TI  - Echo Requests in light of Appropriate Use Criteria.

PMID- 29341523
TI  - ?

PMID- 29341524
TI  - [What's new in Ambulatory General Internal Medicine ?]
AB  - Many treatments are used every day in general medicine without any evidence of
      their efficacy. This last year, three randomised studies tried to prove the
      clinical utility of chondroitin/glucosamine in arthritis, cranberry in urinary
      infections, and acupuncture in migraine. Screening and management of prostate
      cancer are still controversial. Two recent studies help us advising our patients
      on this difficult topic. Muscle side effects from statins are well known and have
      been widely relayed by the press these last years, although myopathies are rare
      in clinical trials. A new study try to determine if negative expectations could
      favor such adverse events.

PMID- 29341525
TI  - [General internal medicine : 2017 scientific breakthroughs in ambulatory care].
AB  - Bariatric surgery improves glycemic control in obese patients with diabetes type
      2. Dual antiplatelet therapy can be maintained beyond 12 months after a
      myocardial infarction. Levothyroxine is not beneficial among patients >= 65 years
      that have subclinical hypothyroidism. Prophylactic anticoagulation in lower limb
      immobilisation should be reserved only for patients with a high risk of
      thromboembolism. A diagnosis of asthma should be initially confirmed by a
      spirometry if clinically suspected. A proton pump inhibitor is indicated for
      patients >= 65 years that are treated with aspirin. Beta-lactams should not be
      avoided in patients with a previous history of non-severe allergy. General
      internists overestimate harms and benefits of common medical tests and
      treatments.

PMID- 29341526
TI  - [The internal medicine articles that struck us the most in 2017].
AB  - 2017 has continued to bring important progress in all areas of internal medicine,
      impacting our daily practice. From bedside screening for beta-lactam allergies,
      to statins as primary prevention in the elderly, SGLT2 inhibitors in heart
      failure, azithromycin in severe asthmatics and tofacitinib in ulcero-haemorrhagic
      recto-colitis, internal medicine journals are full of novelties. Every year, the
      chief residents of the CHUV internal medicine ward meet up to share their
      readings: here is their selection of eleven articles, chosen, summarized and
      commented for you.

PMID- 29341527
TI  - [Recent advances in internal medicine].
AB  - In medicine, there are progresses which radically transform practices, change
      recommendations and win unanimous support in the medical community. There are
      some which divide, questioning principles that seemed established. There are also
      small advances, which can answer the questions that internists ask themselves in
      the daily care of their patients. Here are several articles published in 2017,
      read and commented for you by hospitalists, selected according to their impact on
      the medical world.

PMID- 29341528
TI  - [N-acetylcysteine : effective treatment in severe alcoholic hepatitis ?]
AB  - The use of N-acetylcysteine is of unknown significance when it comes to acute
      liver failure of other origin but for paracetamol overdose. Current data state
      its beneficial use when added to standard treatment for acute alcoholic
      hepatitis, whereas this attitude is less clear for hepatitis of variable other
      origin. This review of literature attends to evaluate and reveal the possible
      interest of adding N-acetylcysteine to standard care of acute liver failure due
      to alcoholism or other non-paracetamol linked causes.

PMID- 29341529
TI  - [When the ward overflows : the impact of outlying beds on patient care].
AB  - Due to the chronic lack of beds in hospitals, patients are often hospitalized in
      other departments (outlier patients), with a responsible physician working in
      another department. This causes increased thromboembolics risks, nosocomial
      infections, falls and delirium in the elderly, morbidity and mortality. Outlier
      patients, compared to standard patients, stay longer in the emergency department
      and their discharge documents are available later. Outlying is used daily in the
      CHUV hospital and new strategies are elaborated to manage patient flow,
      especially during the flu epidemic. The purpose of this article is to review the
      literature on this subject.

PMID- 29341530
TI  - ?

PMID- 29341531
TI  - ?

PMID- 29341532
TI  - ?

PMID- 29341533
TI  - ?

PMID- 29341535
TI  - ?

PMID- 29341534
TI  - ?

PMID- 29341536
TI  - ?

PMID- 29341538
TI  - ?

PMID- 29341537
TI  - ?

PMID- 29341539
TI  - ?

PMID- 29341540
TI  - ?

PMID- 29341541
TI  - Radiotherapy fiber dosimeter probes based on silver-only coated hollow glass
      waveguides.
AB  - Manifestation of Cerenkov radiation as a contaminating signal is a significant
      issue in radiation therapy dose measurement by fiber-coupled scintillator
      dosimeters. To enhance the scintillation signal transmission while minimizing
      Cerenkov radiation contamination, we designed a fiber probe using a silver-only
      coated hollow waveguide (HWG). The HWG with scintillator inserted in its tip,
      embedded in tissue-mimicking phantoms, was irradiated with clinical electron and
      photon beams generated by a medical linear accelerator. Optical spectra of the
      irradiated tip were taken using a fiber spectrometer, and the signal was
      deconvolved with a linear fitting algorithm. The resultant decomposed spectra of
      the scintillator with and without Cerenkov correction were in agreement with
      measurements performed by a standard electron diode and ion chamber for electron
      and photon beam dosimetry, respectively, indicating the minimal effect of
      Cerenkov contamination in the HWG-based dosimeter. Furthermore, compared with a
      silver/dielectric-coated HWG fiber dosimeter design, we observed higher signal
      transmission in the design based on the use of silver-only HWG.

PMID- 29341542
TI  - Intrinsic fluorescence for cervical precancer detection using polarized light
      based in-house fabricated portable device.
AB  - An in-house fabricated portable device has been tested to detect cervical
      precancer through the intrinsic fluorescence from human cervix of the whole
      uterus in a clinical setting. A previously validated technique based on
      simultaneously acquired polarized fluorescence and polarized elastic scattering
      spectra from a turbid medium is used to extract the intrinsic fluorescence. Using
      a diode laser at 405 nm, intrinsic fluorescence of flavin adenine dinucleotide,
      which is the dominant fluorophore and other contributing fluorophores in the
      epithelium of cervical tissue, has been extracted. Different grades of cervical
      precancer (cervical intraepithelial neoplasia; CIN) have been discriminated using
      principal component analysis-based Mahalanobis distance and linear discriminant
      analysis. Normal, CIN I and CIN II samples have been discriminated from one
      another with high sensitivity and specificity at 95% confidence level. This ex
      vivo study with cervix of whole uterus samples immediately after hysterectomy in
      a clinical environment indicates that the in-house fabricated portable device has
      the potential to be used as a screening tool for in vivo precancer detection
      using intrinsic fluorescence.

PMID- 29341543
TI  - Improved axial point spread function in a two-frequency laser scanning confocal
      fluorescence microscope.
AB  - A two-frequency laser scanning confocal fluorescence microscope (TF-LSCFM) based
      on intensity modulated fluorescence signal detection was proposed. The specimen
      induced spherical aberration and scattering effect were suppressed intrinsically,
      and high image contrast was presented due to heterodyne interference. An improved
      axial point spread function in a TF-LSCFM compared with a conventional laser
      scanning confocal fluorescence microscope was demonstrated and discussed.

PMID- 29341544
TI  - ?

PMID- 29341545
TI  - ?

PMID- 29341546
TI  - ?

PMID- 29341547
TI  - ?

PMID- 29341548
TI  - ?

PMID- 29341549
TI  - ?

PMID- 29341550
TI  - Health stewardship: a concept for best health outcomes.
AB  - The concept of health stewardship and responsibility for self, marks a shift from
      adopting a paternalistic approach to care, with decision-making the main remit of
      healthcare practitioners, towards encouraging and empowering individuals to take
      increasing responsibility for their healthcare and outcomes. The main aim of
      nursing is to achieve optimal health outcomes for every patient. Exploring health
      stewardship as a path to wellness will assist healthcare practitioners to guide
      patients living with a chronic disease to be as healthy as possible.

PMID- 29341551
TI  - Reflection on curative treatment versus palliation of symptoms in end of life
      care.
AB  - The conflicting tasks of treating or managing disease and preparing patients and
      their families for the end of life are well documented in haematology and
      palliative care settings. This article is a reflection on practice by a nursing
      student who was in the fourth year of an internship, and discusses a case study
      involving a woman at the end of life. It considers the approach to palliative and
      end of life care adopted in an oncology and haematology ward where there was a
      reluctance to be realistic about the limitations of treatments among some
      healthcare practitioners, who did not want to dispel unrealistic expectations of
      the patient's recovery as a result of continuing treatment. This reflection
      focuses on the care of a patient at the end of life and the frustration
      experienced by the nursing student at their inability to alter the direction of
      treatment from curative treatment to the palliation of symptoms.

PMID- 29341552
TI  - Developing the organisational culture in a healthcare setting.
AB  - This article aims to define organisational culture and explain why it is
      important to patients, carers and those working in healthcare environments.
      Organisational culture is not a new concept and the literature on the subject is
      well-established. However, because of the changing dynamics of the NHS, there has
      been a shift away from 'what' the NHS stands for, often relating to its history
      and rituals, to 'who' it functions for, including how healthcare professionals
      such as nurses can develop and drive the organisational culture. The article
      seeks to assist nurses in understanding the role of organisational culture, as
      well as implementing its main principles in the workplace.

PMID- 29341553
TI  - Pulmonary sequestration mimicring lun cancer: A case report.
AB  - Introduction: Pulmonary sequestration is a rare congenital anomaly and most
      intralobar sequestrations were located in lower lobes. Case report: We reported
      an unusual 28-yearold female patient with intralobar pulmonary sequestration on
      the left lower lobe, successfully treated with lobectomy. Computed tomography
      (CT) of the chest with intravenous contrast revealed multiple clustered cystic
      lesions in the left lower lobe with aberrant artery from descedenting aorta.
      Additional aortography showed an aberrant artery (3 mm in diameter) arising from
      the abdominal aorta and flowing into the lesion. Conclusion: Standard therapy
      regimen for pulmonary sequestration includes surgery. CT scan of thorax with
      intravenous contrast and aortography represent the gold standard for its
      diagnosis. Tumor-like shadows seen on the chest radiography or CT scans should
      not be always suspected on malignant lesions.

PMID- 29341554
TI  - Hyperparathyroidism as a cause of recurrent acute pancreatitis: A case report.
AB  - Introduction: One of the more uncommon etiological factors responsible for the
      development of acute pancreatitis (AP) is hypercalcemia. Hyperparathyroidism
      (HPT), as a cause of hypercalcemia, is responsible for 1.5-13% of AP according to
      a number of studies. A mechanism of the development of AP in hyperparathyroidism
      is still unclear. Case report: We presented a 47-year-old female patient, who had
      five episodes of AP in total before the etiological factors were finally
      determined. The patient had certain comorbidities which were considered to be
      potential causes of AP. She had chronic renal insufficiency (she was on a regular
      hemodialysis program), systemic lupus erythematosus and mioma uteri. She used to
      regularly take an antiepileptic drug (combination of sodium valproate and
      valproic acid). During the fifth episode of AP, the serum calcium level was for
      the first time elevated to twice the normal value. Level of parathyroid hormone
      was several times higher. A static scintigraphy found hyperplasia or
      hyperfunctional adenoma of the right inferior and superior parathyroid glands.
      Abdominal multislice computed tomography (MSCT) scan verified the enlargement of
      the entire pancreas, as well as the presence of heterogeneous structures with
      diffuse amorphous calcifications. The lytic lesions in the pelvic bones could be
      seen in both sides. Parathyroidectomy was being postponed by an endocrine surgeon
      because of the poor overall condition of the patient. In the next period the
      patient had five more episodes of AP. The condition was significantly contributed
      by increasingly more frequent and longer episodes of metrorrhagia. Despite all
      therapeutic measures that were taken, systemic inflammatory response syndrome
      (SIRS) developed, and fatal outcome occurred. Conclusion: In case of recurrent
      pancreatitis, hyperparathyroidism is to be considered even if a significant
      elevation of serum calcium is not present. This is especially the case for
      patients with chronic renal insufficiency or impaired vitamin D metabolism, who
      have a higher risk of secondary hyperthyroidism.

PMID- 29341561
TI  - Massive fetomaternal hemorrhage as a cause of severe fetal anemia.
AB  - Introduction: Fetomaternal hemorrhage (FMH) is a transfu-sion of fetal blood into
      the maternal circulation. A volume of transfused fetal blood required to cause
      severe, life-threatening fetal anemia, is not clearly defined. Some authors
      suggest vol-umes of 80 mL and 150 mL as a threshold which defines mas-sive FMH.
      Therefore, a rate of massive FMH is 1 : 1,000 and 1 : 5,000 births, respectively.
      Fetal and neonatal anemia is one of the most serious complications of the FMH.
      Clinical manifesta-tions of FMH are nonspecific, and mostly it presented as re
      duced fetal movements and changes in cardiotocography (CTG). The standard for
      diagnosing FMH is Kleihaurer-Betke test. Case report: A 34-year-old gravida (G)
      1, para (P) 1 was hospitalized due to uterine contractions at 39 weeks of gesta
      tion. CTG monitoring revealed sinusoidal fetal heart rate and clinical
      examination showed complete cervical dilatation. Im-mediately after admission,
      the women delivered vaginally. Ap-gar scores were 1 and 2 at the first and fifth
      minute, respec-tively. Immediately baby was intubated and mechanical ventila-tion
      started. Initial analysis revealed pronounced acidosis and severe anemia. The
      patient received intravenous fluid therapy with sodium-bicarbonate as well as red
      cell transfusion. With all measures, the condition of the baby improved with
      normaliza-tion of hemoglobin level and blood pH. Kleihaurer-Betke test revealed
      the presence of fetal red cells in maternal circulation, equivalent to 531 mL
      blood loss. The level of maternal fetal hemoglobin (HbF) and elevated alpha
      fetoprotein also con-firmed the diagnosis of massive FMH. Conclusion: For the
      successful diagnosis and management of FMH direct commu-nication between the
      obstetrician and the pediatrician is neces-sary as presented in this report.

PMID- 29341562
TI  - Synchronous mantle cell lymphoma and prostate adenocarcinoma-is it just a
      coincidence?
AB  - Introduction: Synchronous occurrence of lymphomas and other cancers, mostly
      carcinomas are well established. The most of cases describe chronic lymphocytic
      leukemia as the leading lymphoproliferative disease with the tendency towards
      secondary malignancies development. Mantle cell lymphoma (MCL) has been described
      in only 2 cases to co-occur with prostate adenocarcinoma (PAC). There are scarce
      data about the connection between MCL and urology cancers. We presented the first
      case of synchronous occurrence of MCL and PAC in the same patient in Serbia. Case
      report: A 64-year-old male initially presented with fatigue, splenomegaly, and
      bicytopenia. The bone marrow biopsy specimen revealed extensive infiltration with
      MCL. During lymphoma staging procedure prostate enlargement (57 mm) was
      accidentally found by multislice- computed tomography (MSCT). The serum prostate
      specific antigen (PSA) was elevated (52 ng/mL; normal values <= 4 ng/mL).
      Transrectal ultrasound biopsy revealed PAC. High Gleason score determined high
      risk locally advanced PAC. The patient underwent treatment with chemotherapy and
      hormone therapy due to the existence of double malignancies. Cyclophosphamide,
      doxorubicin, vincristine, prednisone (CHOP) was applied for MCL, and luteinizing
      hormonereleasing hormone (LHRH) agonist, triptorelin, for PAC. Partial response
      was obtained for MCL, and stable disease for PAC. In a 1.5-year observation
      period the patient was still disease progression free for both of malignancies.
      Conclusion: This case points aut that elderly males are in need for careful
      observation during the staging procedure for lymphoma. The literature data
      suggest that MCL patients are in increased risk for urologic malignancies
      development. However, the etiologic connection between these two entities, except
      male gender and older age, remains unclear.

PMID- 29341563
TI  - Consumption of antihistamines in Serbia in the period 2011-2015 and the
      correlation with adverse drug reaction reports.

PMID- 29341564
TI  - FMR1 gene mutations cause neurodevelopmental-degenerative disorders: Importance
      of fragile X testing in Serbia

PMID- 29341565
TI  - Psoriasis is the independent factor for early atherosclerosis: A prospective
      study of cardiometabolic risk profile.
AB  - Background/Aim: Psoriasis as multisystemic inflammatory dis-ease is related with
      an increased cardiometabolic risk. The aim of the study was to analyze risk
      biomarkers, peripheral and renal arteries ultrasonography and echocardiography
      for subclinical atherosclerosis and metabolic disease in 106 subjects (66
      psoriasis patients and 40 controls, 20 eczema patients and 20 healthy
      volunteers). Methods: In all exameenes following parameters were analyzed: body
      mass index (BMI), C-reactive protein, D-dimer, serum amyloid A (SAA),
      apolipoprotein (Apo) A1, ApoB, ApoB/Apo A1 index, fasting glucose, C-peptide,
      fasting insulinemia, homeostatic model assessment-insulin resistance (HOMA-IR),
      HOMA-beta-cell, lipid profile, serum uric acid concentration (SUAC), 24-h
      proteinuria and microalbuminuria. Carotid, brachial, femoral and renal arteries
      ultrasonography, as well as echocardiography was also performed. Results: Five of
      66 (7.6%) psoriasis patients had metabolic syndrome (not present in both control
      groups). The following variables were increased in patients with psoriasis
      compared to both control groups: BMI (p = 0.012), insulinemia (p < 0.001), HOMA
      IR (p = 0.003), HOMA-beta cell (p < 0.001), SUAC (p = 0.006), ApoB/ApoA1 ra-tio
      (p = 0.006) and microalbuminuria (p < 0.001). Also, increased C-peptide (p =
      0.034), D-dimer (p = 0.029), triglycerides (p = 0.044), SAA (p = 0.005) and
      decreased ApoA1 (p = 0.014) were found in the psoriasis patients compared to
      healthy controls. HDL cholesterol was decreased in the psoriasis patients
      compared to the control group of eczema patients (p = 0.004). Common carotid
      (CIMT) and femoral artery intima-media thickness (FIMT) was significantly greater
      (p < 0.001) and the maximal flow speed (cm/s) in brachial artery significantly de
      creased (p = 0.017) in the patients with psoriasis in comparison to both control
      groups. In multivariate logistic regression analysis, after the adjustment for
      confounding variables, the most important predictor of CIMT and FIMT was the
      diagnosis of psoriasis (p < 0.001).. Conclusion: Cardiometabolic risk biomarkers
      and ultrasonographic signs of early atherosclerosis are correlated with the
      diagnosis of psoriasis, and not to generalized eczema. Psoriasis was found to be
      an independent risk factor for subclinical atherosclerosis

PMID- 29341566
TI  - Prevalence of dental caries in hospitalized patients with schizophrenia.
AB  - Background/Aim: It is considered that over 450 million people worldwide suffer
      from some form of mental disorder. Previous studies in other countries have shown
      that schizophrenia is among the most frequent. Oral health is significant for
      general health and should not be separated from mental health. Studies in other
      countries have shown an increased incidence of carious and extracted teeth, and
      less incidence of filled teeth in this group of psychiatric patients. The aim of
      this study was to establish condition of the existing teeth, to determine the
      prevalence of caries and to consider possible risk factors that contribute to the
      current oral health status of hospitalized patients with schizophrenia. Methods:
      The study comprised 190 patients with schizophrenia, hospitalized at the Clinic
      for Psychiatric Disorders "Dr. Laza Lazarevic" in Belgrade, and 190 mentally
      healthy patients at the Clinic for Periodontology and Oral Medicine, Faculty of
      Dental Medicine in Belgrade. The decayed, missing, filled (DMF) index,
      sociodemographic and economic characteristics were registered in both groups, as
      well as characteristics of the primary disease of hospitalized patients with
      schizophrenia. Results: The value of DMF index (representing the sum of carious,
      extracted and filled teeth), in the hospitalized patients with schizophrenia was
      18.57 +/- 7.07 and 12.47 +/- 5.64 in the healthy group (p = 0.000). The structure
      of the DMF index in the study group showed that caries and extracted teeth
      dominated with 88.1%; in the control group, filled teeth dominated with 55.6%,
      which was a statistically significant difference for all the three observed
      variables Conclusion: Hospitalized patients with schizophrenia had twice as many
      caries and extracted teeth, and five time less filled teeth than healthy people.
      The patient's age and taking antiparkinsonics were established as predictors of
      the increased DMF index in hospitalized patients with schizophrenia.

PMID- 29341567
TI  - Community-acquired urinary tract infections: Causative agents and their
      resistance to antimicrobial drugs.
AB  - Background/Aim: Urinary tract infections (UTIs) are among the most common
      infections in outpatients. The aim of this study was to define the causative
      agents of urinary tract infections and their resistance to antimicrobial drugs in
      the urban area of central Serbia, as well as to evaluate eventual differences
      associated with age and gender of the patients. Methods: This retrospective study
      analysed data taken from routine, consecutively collected urine cultures of
      outpatients with symptomatic UTIs, collected from the Department of Microbiology,
      Institute of Public Health in Kragujevac, Serbia, from January 2009 to December
      2013. Results: There were 71,905 urine cultures, and 24,713 (34.37%) of them were
      positive for bacterial pathogens. The most common pathogen was Escherichia coli
      (E. coli) (56.56%), followed by Klebsiella spp. (16.20%), Proteus spp. (14.68%),
      Enterococcus spp. (5.29%) and Pseudomonas aeruginosa (3.74%). E. coli and
      Enterococcus spp. isolation rates were lower in males >= 60 years old (23.71% and
      4.87%, respectively), while Klebsiella spp. was more prevalent in this group
      (32.06%). The most common causative agents isolated from 15-29 years old male
      patients were Enterococcus spp. and Pseudomonas aeruginosa (13.28% each). Among
      women, the isolation rate of E.coli was high in all age groups (around 70%).
      Proteus spp. was frequently isolated from females <= 14 years old (13.27%), while
      Klebsiella spp. was the most frequent in the oldest age female group (10.99%).
      Conclusion: Choice of antibiotics for treatment of UTIs should be governed not
      only by the local resistance patterns, but also by gender and age of patients.

PMID- 29341568
TI  - Stigmatization and discrimination of patients with chronic hepatitis C.
AB  - Background/Aim: Chronic hepatitis C (CHC) is often associated with injectable
      drug users and human immunodeficiency virus coinfection for which there is
      stigmatization in society. The aim of this study was to identify the presence of
      stigma and discrimination of patients with CHC, as well as the influence of
      sociodemographic factors on the occurrence of stigmatization. Methods: A cross
      sectional study was performed. Patients with CHC and conducted antiviral therapy
      completed an anonymous structured questionnaire consisting of sociodemographic
      questions and Hepatitis C stigma scale. Results: Out of 154 patients 61.7% were
      male and 72.1% from the city; 59.7% have completed secondary school; 61.7% were
      employed before the disease while 31.8% after the disease; 45.5% were
      unsatisfactory with financial situation; 54.5% were married; 37.7% lived with a
      spouse and children; 86.4% in their own house/apartment; 5.2% of the patients
      were abandoned by their partners, while 35.7% consumed drugs. A statistical
      significance of the stigma score was found in those who lived in the city (p =
      0.018), unmarried (p = 0.005), abandoned by the partners after the diagnosis of
      CHC (p < 0.001), drug users (p = 0.002) and those living with parents (p =
      0.034). Univariate regression analysis singled out as significant: residence (p =
      0.018), living with their parents (p = 0.046), abandonment by a partner (p <
      0.001) and drug use (p = 0.002). A multivariate regression model of independent
      variables singled out abandonment by partners (Beta = 5.158, p = 0.007). Men
      disagree significantly with the two elements inside stigma [not the same as the
      others (p = 0.035)] and hurt by the reaction of others (p = 0.047)). Conclusion:
      The presence of stigma in patients with CHC was proven. The results indicate the
      need to strengthen anti-stigma programs that will reduce their psychological and
      social problems and reduce stigmatization in society.

PMID- 29341569
TI  - Agreement between admission and discharge diagnoses: Analysis by the groups of
      international classification of diseases, 10th revision.
AB  - Background/Aim: Admission diagnosis represents the diagnosis of an illness,
      injury or condition due to which a patient is referred to hospital to be
      admitted. Discharge diagnosis represents the main reason of illness or condition
      due to which a patient is admitted. The aim of this study was to analyze the
      agreement between admission diagnostic groups and discharge diagnostic groups of
      patients in the Clinical Center Kragujevac in the period from January 1, 2006 to
      December 31, 2013 on the basis of the hospitalization report. Methods: From the
      basic set of reports, 5% of random samples were singled out and they contained
      20,422 reports. Out of the given number of reports, 18,173 hospitalization
      reports were complete and then further analyzed in the paper. Admission
      diagnostic groups given by the primary care doctor were compared with discharge
      diagnostic groups filled out by the practicing physician in the hospital ward
      from which a patient was discharged. The agreement of these two diagnostic groups
      was an indication of the high-quality performance of the primary care doctor.
      Agreement analysis was conducted using Cohen's Kappa statistics. Restuls:
      Agreement analysis showed that the values of the Kappa coefficient for the five
      leading admission diagnostic groups were in the range of kappa = 0.61 to kappa =
      0.94. The values of the Kappa coefficient for the five most common discharge
      diagnostic groups were in the range of kappa = 0.55 to kappa = 0.81. Conclusion:
      Hospitalization report is a reliable individual report on inpatient care, so it
      could be used in determining the degree of agreement between admission diagnostic
      groups and discharge diagnostic groups.

PMID- 29341570
TI  - Histomorphometric evaluation of bone regeneration using autogenous bone and beta
      tricalcium phosphate in diabetic rabbits.
AB  - Background/Aim: The mechanism of impaired bone healing in diabetes mellitus
      includes different tissue and cellular level activities due to micro- and
      macrovascular changes. As a chronic metabolic disease with vascular
      complications, diabetes affects a process of bone regeneration as well. The
      therapeutic approach in bone regeneration is based on the use of osteoinductive
      autogenous grafts as well as osteoconductive synthetic material, like a beta
      tricalcium phosphate. The aim of the study was to determine the quality and
      quantity of new bone formation after the use of autogenous bone and beta
      tricalcium phosphate in the model of calvarial critical-sized defect in rabbits
      with induced diabetes mellitus type I. Methods: The study included eight 4-month
      old Chincilla rabbits with alloxan-induced diabetes mellitus type I. In all
      animals, there were surgically created two calvarial bilateral defects (diameter
      12 mm), which were grafted with autogenous bone and beta-tricalcium phosphate (n
      = 4) or served as unfilled controls (n = 4). After 4 weeks of healing, animals
      were sacrificed and calvarial bone blocks were taken for histologic and
      histomorphometric analysis. Beside descriptive histologic evaluation, the
      percentage of new bone formation, connective tissue and residual graft were
      calculated. All parameters were statistically evaluated by Friedman Test and post
      hock Wilcoxon Singed Ranks Test with a significance of p < 0.05. Results:
      Histology revealed active new bone formation peripherally with centrally located
      connective tissue, newly formed woven bone and well incorporated residual grafts
      in all treated defects. Control samples showed no bone bridging of defects. There
      was a significantly more new bone in autogeonous graft (53%) compared with beta
      tricalcium phosphate (30%), (p < 0.030) and control (7%), (p < 0.000) groups. A
      significant difference was also recorded between beta-tricalcium phosphate and
      control groups (p < 0.008). Conclusion: In the present study on the rabbit
      grafting model with induced diabetes mellitus type I, the effective bone
      regeneration of critical bone defects was obtained using autogenous bone graft.
      [Projekat Ministarstva nauke Republike Srbije, br. 175021].

PMID- 29341571
TI  - Diagnostic accuracy of the A-test and cutoff points for assessing outcomes and
      planning acute and post-acute rehabilitation of patients surgically treated for
      hip fractures and osteoarthritis.
AB  - Background/Aim: The A-test is used in daily clinical practice for monitoring
      functional recovery of orthopedic patients during early rehabilitation. The aim
      of this study was to determine the accuracy of A-test and cutoff point at which
      the test can separate patients with and without functional disability at the end
      of early rehabilitation. Also, it was important to determine whether A-test has
      that discriminative ability (and at which cutoff points) in the first days of
      early rehabilitation in order to have time to plan post acute rehabilitation.
      Methods: This measurement-focused study was conducted in the Orthopedic Ward
      during early inpatient rehabilitation (1st-5th day after the operation) of 60
      patients with hip osteoarthritis (HO) that underwent arthroplasty and 60
      surgically treated patients with hip fracture (HF). For measurements we used the
      A-test and the University of Iowa Level of Assistance Scale (ILAS) as the gold
      standard. For statistical analysis we used the receiver operating characteristic
      (ROC) curve and the area under the curve (AUC) with 95% confidence interval for
      the results of A-test from the first to the fifth day of rehabilitation,
      sensitivity, specificity, the rate of false positive and false negative errors,
      positive and negative predictive value, ratio of positive and negative likelihood
      ratio, accuracy, point to the ROC curve closest to 0.1 and Youden index for all
      the cutoff points. Results: The AUC was 0.825 (0.744-0.905) for the first day of
      rehabilitation, 0.922 (0.872-0.972) for the second day of rehabilitation, 0.980
      (0.959-1.000) for the third day of rehabilitation, 0.989 (0.973-1.004) for the
      fourth day, and 0.999 (0.996-1.001) for the fifth day of rehabilitation. The
      optimal cutoff for the results of A-test was: 7/8 for the first day, 29/30 for
      the fourth day, and 34/35 for the fifth day of rehabilitation. On the second and
      the third day A-test had two cutoff points, the lower point safely separated the
      patients with functional disability, while the upper point ruled out functional
      disability. On the 2nd rehabilitation day the cutoff points were 12/13 and 17/18,
      on the 3rd rehabilitation day cutoff points were 13/14 and 18/19. Conclusion: The
      A-test has all characteristics of an accurate tool which can be used for
      separating patients with and without functional disability at all stages of early
      rehabilitation after surgically treated hip disease or fracture. Based on the
      results of A-test within the first days of early rehabilitation, it is possible
      to make a plan for postacute rehabilitation.

PMID- 29341572
TI  - Risk factors for cardiovascular disease in children on chronic hemodialysis:
      Traditional (general) risk factors, Part I.

PMID- 29341573
TI  - Classification and the diagnostics of abnormal uterine bleeding in nongravid
      women of reproductive age: The PALM-COEIN classification system adopted by the
      International Federation of Gynecology and Obstetrics.

PMID- 29341574
TI  - Bullous lung diseases as a risk factor for lung cancer: A case report.
AB  - Introduction: A possible association between lung cancer and bullous lung disease
      has been suggested and recently supported by the results of genetic studies. Case
      report: A previously healthy 43-year-old man, smoker, was diagnosed with bullous
      lung disease at the age of 31 years. He was followed up for 12 years when lung
      cancer (adenocarcinoma) was found at the site. In the meantime, he was treated
      for recurrent respiratory infections. Conclusion: There is the need for active
      approach in following up the patients with pulmonary bulla for potential
      development of lung cancer.

PMID- 29341575
TI  - Severe vaso-occlusive retinopathy associated with systemic lupus erythematosus.
AB  - Introduction: Systemic lupus erythematosus (SLE) is a systemic idiopathic
      autoimmune inflammatory disease, with multiple organ involvement. Severe vaso
      occlusive retinopathy is a rare, sight threatening lupus-related manifestation of
      the disease, which is more common in patients with coexisting antiphospholipid
      syndrome. Case report: We reported a 36-year-old female with severe vaso
      occlusive retinopathy that manifested in the absence of antiphospholipid
      syndrome. In a 4-year follow-up, despite aggressive systemic corticosteroid and
      immunosuppressive therapy and panretinal laserphotocoagulation treatment, the
      disease progressed to retinal neovascularisation, neovascular vitreoretinopathy,
      neovascular glaucoma and, consecutively, severe visual loss. As the final option
      for preservation of visual function, pars plana vitrectomy with
      laserphotocoagulation was performed and had good results. Progression of
      ophthalmological findings indicated the progression of the systemic disease, as
      well as neurolupus. Conclusion: Severe vaso-occlusive retinopathy occurred as the
      ophthalmological manifestation of SLE in the absence of antiphospholipid
      syndrome, but correlated with neurolupus and led to visual deterioration despite
      the treatment.

PMID- 29341576
TI  - Pseudomesotheliomatous carcinoma of the lung.
AB  - Introduction: Pseudomesotheliomatous lung carcinoma is a special, rare entity
      characterized by large pleural growth and minor invasion of lung tissue.
      Clinically, radiologically, macroscopically and even histologically this tumor
      can be misdiagnosed as malignant pleural carcinoma. Case report: We represent a
      64-year-old male patient, former smoker. Due to difficulties in the form of dry
      cough, feeling of dis-comfort and pain in the right hemithorax, fatigue, heavy
      breathing, sweating, fever up to 39.6 degrees C the patient was treated as with
      combined antibiotic therapy (macrolides, cephalosporins and penicillin), but
      without improving of his condition. Chest radiography showed a shadow of pleural
      effusion by the height of the front end of the third right rib. Chest MSCT showed
      the extremely thickened pleura apically and to the posterior along the upper
      right lobe in addition to existence of massive pleural effusion. Subpleural
      condensation of parenchyma ranging about 30 mm was described in the upper right
      lobe. Cytological analysis of the pleural effusion showed the presence of
      malignant cells impossible to differentiate whether they were metastasis of
      adenocarcinoma or malignant pleural mesothelioma. By histochemical and
      immunohistohemical analyses of a pleural sample, pseudomesotheliomataus lung
      adenocarcinoma was diagnosed. Conclusion: Pseudomesotheliomataus carcinoma of the
      lungs can be a diagnostic problem. Its diagnosis is based on recognition of
      histopathological characteristics which enable its discernment from the
      epithelial variant of malignant pleural mesothelioma.

PMID- 29341577
TI  - Apical root-end filling with tricalcium silicate-based cement in a patient with
      diabetes mellitus: A case report.
AB  - Introduction: The material used for root-end filling has to be biocompatible with
      adjacent periapical tissue and to stimulate its regenerative processes.
      Tricalcium silicate cement (TSC), as a new dental material, shows good sealing
      properties with dentin, high compression strengths and better marginal adaptation
      than commonly used root-end filling materials. Although optimal postoperative
      healing of periapical tissues is mainly influenced by characteristics of end-root
      material used, it could sometimes be affected by the influence of systemic
      diseases, such as diabetes mellitus (DM). Case report: We presented apical
      healing of the upper central incisor, retrofilled with TSC, in a diabetic patient
      (type 2 DM) with peripheral neuropathy. Standard root-end resection of upper
      central incisor was accompanied by retropreparation using ultrasonic retrotips to
      the depth of 3 mm and retrofilling with TSC. Post-operatively, the surgical wound
      healed uneventfully. However, the patient reported undefined dull pain in the
      operated area that could possibly be attributed to undiagnosed intraoral diabetic
      peripheral neuropathy, what was evaluated clinically. Conclusion: Although TSC
      presents a suitable material for apical root-end filling in the treatment of
      chronic periradicular lesions a possible presence of systemic diseases, like type
      2 DM, has to be considered in the treatment outcome estimation.

PMID- 29341578
TI  - Case report of gross hematuria in the nutcracker syndrome resolved by renocaval
      reimplantation.
AB  - Introduction: Nutcracker syndrome is defined as a set of signs and symptoms
      secondary to compression of the left renal vein (LRV) in the acute anatomic angle
      between the aorta and its superior mesenteric branch. Case report: A 38-year old
      woman with asymptomatic and "idiopathic" gross hematuria came to the Clinic for
      Vascular and Endovascular Surgery, Clinical Center of Serbia in Belgrade.
      Hematuria was documented by cystoscopy and was found to be unilateral, located to
      the left urethral orifice. The contrast-enhanced multidetector computed
      tomography (MDCT) scan showed a stenotic LRV due to the extrinsic compression in
      the angle formed by the ventral aorta and superior mesenteric artery (MSA), with
      a jet of contrast through the lumen. Considering the negative investigations for
      more common causes of hematuria, its incapacitating nature, and above mentioned
      imaging findings suggestive of the nutcracker syndrome, an indication for the
      open surgical correction of the LRV entrapment was established. The patient
      underwent reimplantation of the LRV into the more distal inferior vena cava
      (IVC), to relocate it out of the constrictive aortomesenteric space.
      Intraoperative findings were notable for blood flow turbulence in the LRV and
      hypertrophy of its tributaries, which were ligated. We presented the first
      published case in the Serbian literature on nutcracker syndrome with hematuria
      resolved by renocaval reimplantation. Conclusion: This case report demonstrates
      that renocaval reimplantation, as the open surgery technique, could be the
      adequate method for resolving gross hematuria in patients with nutcracker
      syndrome.

PMID- 29341579
TI  - Nanoparticulate Contrast Agents for Multimodality Molecular Imaging.
AB  - Molecular imaging is rapidly developing as a powerful tool in research and
      medical diagnostic. By integrating complementary signal reporters into a single
      nanoparticulate contrast agent, multimodal molecular imaging can be performed as
      scalable images with high sensitivity, resolution and specificity. In this
      review, multifunctional nanoparticles (MFNPs) are classified into four types:
      conjugation, encapsulation, core/shell, and co-doping. Further, new constructs of
      MFNPs were reported recently which have used nanoparticulate contrast agent such
      as quantum dots (QDs), iron oxide nanoparticles (IONPs), Upconversion
      nanoparticles (UCNPs), carbon based nanoparticles, gold nanoparticles (Au-NPs),
      Metal-Organic Frameworks (MOFs), dendrimers and porphyrins based nanoparticles.
      Different surface modification strategies were also developed as well as ligands
      are attached to those NPs to render the biocompatibility and enable specific
      targeting. These new development in MFNPs are expected to introduce a paradigm
      shift in multi-modal molecular imaging and thereby opening up an era of
      personalized medicine and new diagnostic medical imaging tools.

PMID- 29341580
TI  - Hippocrates-The father of modern medicine.

PMID- 29341581
TI  - Functional Chitosan Nanoparticles in Cancer Treatment.
AB  - With exponential growth in nanotechnology and material chemistry, the application
      of a variety of nanomaterials in biomedical field has attracted increasing
      interest, especially in cancer diagnosis and treatment. Nanoparticles have
      greatly revolutionized the therapy pattern of cancer owing to their specific
      targeting ability, prolonged circulation time, enhanced therapeutic efficacy, and
      decreased systemic side effects. Chitosan, a modified natural polysaccharide with
      excellent biocompatibility, has been intensively studied for use as carriers to
      deliver various drugs and genes in cancer treatment. This review provides an
      insight into the advances in chitosan-based nanoparticles with a focus on its
      therapeutic potential in cancer treatment.

PMID- 29341582
TI  - In-Plane Channel-Structured Catalyst Layer for Polymer Electrolyte Membrane Fuel
      Cells.
AB  - In this study, we present a novel catalyst layer (CL) with in-plane flow channels
      to enhance the mass transports in polymer electrolyte membrane fuel cells. The CL
      with in-plane channels on its surface is fabricated by coating a CL slurry onto a
      surface-treated substrate with the inverse line pattern and transferring the
      dried CL from the substrate to a membrane. The membrane electrode assembly with
      the in-plane channel-patterned CL has superior power performances in high current
      densities compared with an unpatterned, flat CL, demonstrating a significant
      enhancement of the mass-transport property by the in-plane channels carved in the
      CL. The performance gain is more pronounced when the channel direction is
      perpendicular to the flow field direction, indicating that the in-plane channels
      increase the utilization of the CL under the rib area. An oxygen-transport
      resistance analysis shows that both molecular and Knudsen diffusion can be
      facilitated with the introduction of the in-plane channels. The direct CL
      patterning technique provides a platform for the fabrication of advanced CL
      structures with a high structural fidelity and design flexibility and a rational
      guideline for designing high-performance CLs.

PMID- 29341583
TI  - Tumor Catalytic-Photothermal Therapy with Yolk-Shell Gold@Carbon Nanozymes.
AB  - Nanozymes, as a new generation of artificial enzymes, offer great opportunities
      in biomedical engineering and disease treatment. Synergizing the multiple
      intrinsic functions of nanozymes can improve their performance in biological
      systems. Here, we report a novel nanozyme with yolk-shell structure fabricated by
      combining a single gold nanoparticle core with a porous hollow carbon shell
      nanospheres (Au@HCNs). Au@HCNs exhibited enzyme-like activities similar to
      horseradish peroxidase and oxidase under an acidic environment, showing the
      ability of ROS generation. More importantly, the ROS production of Au@HCNs was
      significantly improved upon 808 nm light irradiation by the photothermal effect,
      which is often used for tumor therapy. Cellular and animal studies further
      demonstrated that the efficient tumor destruction was achieved through the
      combination of light-enhanced ROS and photothermal therapy. These results implied
      that the intrinsic enzyme-like activity and photothermal conversion of nanozymes
      can be synergized for efficient tumor treatment, providing a proof-of-concept of
      tumor catalytic-photothermal therapy based on nanozymes.

PMID- 29341584
TI  - Preparation of a Smart and Portable Film for in Situ Sensing of Iron
      Microcorrosion.
AB  - Corrosion of iron-containing materials, which presents serious economic and
      safety problems, normally begins with microcorrosion, which refers to the early
      stages of corrosion before visible changes appear on the surface. If
      microcorrosion could be detected and repaired immediately, corrosion damage could
      be greatly reduced. Current technology and materials, however, are not able to
      detect microcorrosion of iron in a cheap and convenient manner. Here, we have
      used a natural product, ellagic acid (EA), to fabricate an EA-functionalized
      poly(vinyl alcohol) (PVA) film (EAF) for in situ sensing of the initial stage of
      microcorrosion. EAF was able to effectively sense iron microcorrosion via an
      obvious color change. The film also had good long-term stability and mechanical
      strength. Since EAF can be easily prepared from inexpensive and green raw
      materials, the film opens up a new opportunity for the detection of iron
      microcorrosion.

PMID- 29341585
TI  - Self-Powered Microfluidic Transport System Based on Triboelectric Nanogenerator
      and Electrowetting Technique.
AB  - Electrowetting technique is an actuation method for manipulating position and
      velocity of fluids in the microchannels. By combining electrowetting technique
      and a freestanding mode triboelectric nanogenerator (TENG), we have designed a
      self-powered microfluidic transport system. In this system, a mini vehicle is
      fabricated by using four droplets to carry a pallet (6 mm * 8 mm), and it can
      transport some tiny object on the track electrodes under the drive of TENG. The
      motion of TENG can provide both driving power and control signal for the mini
      vehicle. The maximum load for this mini vehicle is 500 mg, and its highest
      controllable velocity can reach 1 m/s. Freestanding TENG has shown excellent
      capability to manipulate microfluid. Under the drive of TENG, the minimum volume
      of the droplet can reach 70-80 nL, while the tiny droplet can freely move on both
      horizontal and vertical planes. Finally, another strategy for delivering
      nanoparticles to the designated position has also been demonstrated. This
      proposed self-powered transport technique may have great applications in the
      field of microsolid/liquid manipulators, drug delivery systems, microrobotics,
      and human-machine interactions.

PMID- 29341586
TI  - Development of a Cytopathic Effect-Based Phenotypic Screening Assay against
      Cryptosporidium.
AB  - Cryptosporidiosis is a diarrheal disease predominantly caused by Cryptosporidium
      parvum ( Cp) and Cryptosporidium hominis ( Ch), apicomplexan parasites which
      infect the intestinal epithelial cells of their human hosts. The only approved
      drug for cryptosporidiosis is nitazoxanide, which shows limited efficacy in
      immunocompromised children, the most vulnerable patient population. Thus, new
      therapeutics and in vitro infection models are urgently needed to address the
      current unmet medical need. Toward this aim, we have developed novel cytopathic
      effect (CPE)-based Cp and Ch assays in human colonic tumor (HCT-8) cells and
      compared them to traditional imaging formats. Further model validation was
      achieved through screening a collection of FDA-approved drugs and confirming many
      previously known anti- Cryptosporidium hits as well as identifying a few novel
      candidates. Collectively, our data reveals this model to be a simple, functional,
      and homogeneous gain of signal format amenable to high throughput screening,
      opening new avenues for the discovery of novel anticryptosporidials.

PMID- 29341587
TI  - Fucoidan Prolongs the Circulation Time of Dextran-Coated Iron Oxide
      Nanoparticles.
AB  - The magnetic properties and safety of dextran-coated superparamagnetic iron oxide
      nanoparticles (SPIONs) have facilitated their clinical use as MRI contrast agents
      and stimulated research on applications for SPIONs in particle imaging and
      magnetic hyperthermia. The wider clinical potential of SPIONs, however, has been
      limited by their rapid removal from circulation via the reticuloendothelial
      system (RES). We explored the possibility of extending SPION circulatory time
      using fucoidan, a seaweed-derived food supplement, to inhibit RES uptake. The
      effects of fucoidan on SPION biodistribution were evaluated using ferucarbotran,
      which in its pharmaceutical formulation (Resovist) targets the RES. Ferucarbotran
      was radiolabeled at the iron oxide core with technetium-99m (99mTc; t1/2 = 6 h)
      or zirconium-89 (89Zr; t1/2 = 3.3 days). Results obtained with 99mTc
      ferucarbotran demonstrated that administration of fucoidan led to a 4-fold
      increase in the circulatory half-life (t1/2 slow) from 37.4 to 150 min (n = 4; P
      < 0.0001). To investigate whether a longer circulatory half-life could lead to
      concomitant increased tumor uptake, the effects of fucoidan were tested with 89Zr
      ferucarbotran in mice bearing syngeneic subcutaneous (GL261) tumors. In this
      model, the longer circulatory half-life achieved with fucoidan was associated
      with a doubling in tumor SPION uptake (n = 5; P < 0.001). Fucoidan was also
      effective in significantly increasing the circulatory half-life of perimag-COOH,
      a commercially available SPION with a larger hydrodynamic size (130 nm) than
      ferucarbotran (65 nm). These findings indicate successful diversion of SPIONs
      away from the hepatic RES and show realistic potential for future clinical
      applications.

PMID- 29341588
TI  - Human Neuraminidase Isoenzymes Show Variable Activities for 9- O-Acetyl-sialoside
      Substrates.
AB  - Recognition of terminal sialic acids is central to many cellular processes, and
      structural modification of sialic acid can disrupt these interactions. A
      prominent, naturally occurring, modification of sialic acid is 9- O-acetylation
      (9- O-Ac). Study of this modification through generation and analysis of 9- O-Ac
      sialosides is challenging because of the lability of the acetate group.
      Fundamental questions regarding the role of 9- O-Ac sialic acids remain
      unanswered, including what effect it may have on recognition and hydrolysis by
      the human neuraminidase enzymes (hNEU). To investigate the substrate activity of
      9- O-acetylated sialic acids (Neu5,9Ac2), we synthesized an acetylated
      fluorogenic hNEU substrate 2'-(4-methylumbelliferyl)-9- O-acetyl-alpha-d- N
      acetylneuraminic acid. Additionally, we generated a panel of octyl
      sialyllactosides containing modified sialic acids including variation in linkage,
      9- O-acetylation, and C-5 group (Neu5Gc). Relative rates of substrate cleavage by
      hNEU were determined using fluorescence spectroscopy and electrospray ionization
      mass spectrometry. We report that 9- O-acetylation had a significant, and
      differential, impact on sialic acid hydrolysis by hNEU with general substrate
      tolerance following the trend of Neu5Ac > Neu5Gc ? Neu5,9Ac2 for NEU2, NEU3, and
      NEU4. Both NEU2 and NEU3 had remarkably reduced activity for Neu5,9Ac2 containing
      substrates. Other isoenzymes appeared to be more tolerant, with NEU4 even showing
      increased activity on Neu5,9Ac2 substrates with an aryl aglycone. The impact of
      these minor structural changes to sialic acid on hNEU activity was unexpected,
      and these results provide evidence of the substantial influence of 9- O-Ac
      modifications on hNEU enzyme substrate specificity. Furthermore, these findings
      may implicate hNEU in processes governed by 9- O-acetyltransferases and 
      esterases.

PMID- 29341589
TI  - Metal-Organic Frameworks-Derived Hierarchical Co3O4 Structures as Efficient
      Sensing Materials for Acetone Detection.
AB  - Highly sensitive and stable gas sensors have attracted much attention because
      they are the key to innovations in the fields of environment, health, energy
      savings and security, etc. Sensing materials, which influence the practical
      sensing performance, are the crucial parts for gas sensors. Metal-organic
      frameworks (MOFs) are considered as alluring sensing materials for gas sensors
      because of the possession of high specific surface area, unique morphology,
      abundant metal sites, and functional linkers. Herein, four kinds of porous
      hierarchical Co3O4 structures have been selectively controlled by optimizing the
      thermal decomposition (temperature, rate, and atmosphere) using ZIF-67 as
      precursor that was obtained from coprecipitation method with the co-assistance of
      cobalt salt and 2-methylimidazole in the solution of methanol. These hierarchical
      Co3O4 structures, with controllable cross-linked channels, meso-/micropores, and
      adjustable surface area, are efficient catalytic materials for gas sensing.
      Benefits from structural advantages, core-shell, and porous core-shell Co3O4
      exhibit enhanced sensing performance compared to those of porous popcorn and
      nanoparticle Co3O4 to acetone gas. These novel MOF-templated Co3O4 hierarchical
      structures are so fantastic that they can be expected to be efficient sensing
      materials for development of low-temperature operating gas sensors.

PMID- 29341590
TI  - Correction to Fourier Transform Infrared Studies on the Dissociation Behavior of
      Metal-Chelating Polyelectrolyte Brushes.

PMID- 29341591
TI  - The Development of Benzimidazole-Based Clickable Probes for the Efficient
      Labeling of Cellular Protein Arginine Deiminases (PADs).
AB  - Citrullination is the post-translational hydrolysis of peptidyl-arginines to form
      peptidyl-citrulline, a reaction that is catalyzed by the protein arginine
      deiminases (PADs), a family of calcium-regulated enzymes. Aberrantly increased
      protein citrullination is associated with a slew of autoimmune diseases (e.g.,
      rheumatoid arthritis (RA), multiple sclerosis, lupus, and ulcerative colitis) and
      certain cancers. Given the clear link between increased PAD activity and human
      disease, the PADs are therapeutically relevant targets. Herein, we report the
      development of next generation cell permeable and "clickable" probes (BB-Cl-Yne
      and BB-F-Yne) for covalent labeling of the PADs both in vitro and in cell-based
      systems. Using advanced chemoproteomic technologies, we also report the off
      targets of both BB-Cl-Yne and BB-F-Yne. The probes are highly specific for the
      PADs, with relatively few off targets, especially BB-F-Yne, suggesting the
      preferential use of the fluoroacetamidine warhead in next generation irreversible
      PAD inhibitors. Notably, these compounds can be used in a variety of modalities,
      including the identification of off targets of the parent compounds and as
      activity-based protein profiling probes in target engagement assays to
      demonstrate the efficacy of PAD inhibitors.

PMID- 29341592
TI  - Application of Decafluorobiphenyl (DFBP) Moiety as a Linker in Bioconjugation.
AB  - Considerable attention has been devoted to fluorinated compounds due to their
      unique and interesting properties. Many modern pharmaceuticals contain
      fluorinated substituents, which are commonly synthesized using selective
      fluorinating reagents. Decafluorobiphenyl (DFBP) as a fluorinated linker is
      susceptible to nucleophilic attack. This nucleophilic reaction has been widely
      studied using various nucleophiles. Sulfur and nitrogen containing nucleophiles
      have been of particular interest, especially in bioconjugated reactions. This
      review focuses on the SNAr reactivity of DFBP in formation of C-X (X = S, N)
      bonds, to be applied in bioconjugation in organic chemistry. The review aims to
      highlight the crucial factors that govern the chemistry behind the activation of
      F-CAr-CAr-F bonds as a linker in the synthesis of novel peptides, proteins, and
      biologics.

PMID- 29341593
TI  - Analysis of Cellular Tyrosine Phosphorylation via Chemical Rescue of
      Conditionally Active Abl Kinase.
AB  - Identifying direct substrates targeted by protein kinases is important in
      understanding cellular physiology and intracellular signal transduction. Mass
      spectrometry-based quantitative proteomics provides a powerful tool for
      comprehensively characterizing the downstream substrates of protein kinases. This
      approach is efficiently applied to receptor kinases that can be precisely,
      directly, and rapidly activated by some agent, such as a growth factor. However,
      nonreceptor tyrosine kinase Abl lacks the experimental advantage of extracellular
      growth factors as immediate and direct stimuli. To circumvent this limitation, we
      combine a chemical rescue approach with quantitative phosphoproteomics to
      identify targets of Abl and their phosphorylation sites with enhanced temporal
      resolution. Both known and novel putative substrates are identified, presenting
      opportunities for studying unanticipated functions of Abl under physiological and
      pathological conditions.

PMID- 29341595
TI  - Self-Healing Hydrogels of Low Molecular Weight Poly(vinyl alcohol) Assembled by
      Host-Guest Recognition.
AB  - Poly(vinyl alcohol) (PVA) is a cytocompatible synthetic polymer and has been
      commonly used to prepare hydrogels. Bile acids and beta-cyclodextrin are both
      natural compounds and they form stable host-guest inclusion complexes. They are
      attached covalently onto a low molecular weight PVA separately. Self-healing
      hydrogels can be easily formed by mixing the aqueous solutions of these PVA based
      polymers. The mechanical properties of the hydrogels can be tuned by varying the
      molar fractions of bile acid units on PVA. The dynamic inclusion complexation of
      the host-guest pair of the hydrogel allows the self-healing rapidly under ambient
      atmosphere and their mechanical properties could recover their original values in
      1 min after incision. These PVA based polymers exhibited the good
      cytocompatibility and high hemocompatibility as shown by their biological
      evaluations. The use of natural compounds for host-guest interaction make such
      gels especially convenient to use as biomaterials, an advantage over conventional
      hydrogels prepared through freeze-thaw method.

PMID- 29341596
TI  - Core-Shell ZIF-8@ZIF-67-Derived CoP Nanoparticle-Embedded N-Doped Carbon Nanotube
      Hollow Polyhedron for Efficient Overall Water Splitting.
AB  - The construction of highly active and stable non-noble-metal electrocatalysts for
      hydrogen and oxygen evolution reactions is a major challenge for overall water
      splitting. Herein, we report a novel hybrid nanostructure with CoP nanoparticles
      (NPs) embedded in a N-doped carbon nanotube hollow polyhedron (NCNHP) through a
      pyrolysis-oxidation-phosphidation strategy derived from core-shell ZIF-8@ZIF-67.
      Benefiting from the synergistic effects between highly active CoP NPs and NCNHP,
      the CoP/NCNHP hybrid exhibited outstanding bifunctional electrocatalytic
      performances. When the CoP/NCNHP was employed as both the anode and cathode for
      overall water splitting, a potential as low as 1.64 V was needed to achieve the
      current density of 10 mA.cm-2, and it still exhibited superior activity after
      continuously working for 36 h with nearly negligible decay in potential. Density
      functional theory calculations indicated that the electron transfer from NCNHP to
      CoP could increase the electronic states of the Co d-orbital around the Fermi
      level, which could increase the binding strength with H and therefore improve the
      electrocatalytic performance. The strong stability is attributed to high
      oxidation resistance of the CoP surface protected by the NCNHP.

PMID- 29341594
TI  - Designing Flavoprotein-GFP Fusion Probes for Analyte-Specific Ratiometric
      Fluorescence Imaging.
AB  - The development of genetically encoded fluorescent probes for analyte-specific
      imaging has revolutionized our understanding of intracellular processes. Current
      classes of intracellular probes depend on the selection of binding domains that
      either undergo conformational changes on analyte binding or can be linked to
      thiol redox chemistry. Here we have designed novel probes by fusing a
      flavoenzyme, whose fluorescence is quenched on reduction by the analyte of
      interest, with a GFP domain to allow for rapid and specific ratiometric sensing.
      Two flavoproteins, Escherichia coli thioredoxin reductase and Saccharomyces
      cerevisiae lipoamide dehydrogenase, were successfully developed into thioredoxin
      and NAD+/NADH specific probes, respectively, and their performance was evaluated
      in vitro and in vivo. A flow cell format, which allowed dynamic measurements, was
      utilized in both bacterial and mammalian systems. In E. coli the first reported
      intracellular steady-state of the cytoplasmic thioredoxin pool was measured. In
      HEK293T mammalian cells, the steady-state cytosolic ratio of NAD+/NADH induced by
      glucose was determined. These genetically encoded fluorescent constructs
      represent a modular approach to intracellular probe design that should extend the
      range of metabolites that can be quantitated in live cells.

PMID- 29341597
TI  - The WYL Domain of the PIF1 Helicase from the Thermophilic Bacterium Thermotoga
      elfii is an Accessory Single-Stranded DNA Binding Module.
AB  - PIF1 family helicases are conserved from bacteria to man. With the exception of
      the well-studied yeast PIF1 helicases (e.g., ScPif1 and ScRrm3), however, very
      little is known about how these enzymes help maintain genome stability. Indeed,
      we lack a basic understanding of the protein domains found N- and C-terminal to
      the characteristic central PIF1 helicase domain in these proteins. Here, using
      chimeric constructs, we show that the ScPif1 and ScRrm3 helicase domains are
      interchangeable and that the N-terminus of ScRrm3 is important for its function
      in vivo. This suggests that PIF1 family helicases evolved functional modules
      fused to a generic motor domain. To investigate this hypothesis, we characterized
      the biochemical activities of the PIF1 helicase from the thermophilic bacterium
      Thermotoga elfii (TePif1), which contains a C-terminal WYL domain of unknown
      function. Like helicases from other thermophiles, recombinant TePif1 was easily
      prepared, thermostable in vitro, and displayed activities similar to its
      eukaryotic homologues. We also found that the WYL domain was necessary for high
      affinity single-stranded DNA (ssDNA) binding and affected both ATPase and
      helicase activities. Deleting the WYL domain from TePif1 or mutating conserved
      residues in the predicted ssDNA binding site uncoupled ATPase activity and DNA
      unwinding, leading to higher rates of ATP hydrolysis but less efficient DNA
      helicase activity. Our findings suggest that the domains of unknown function
      found in eukaryotic PIF1 helicases may also confer functional specificity and
      additional activities to these enzymes, which should be investigated in future
      work.

PMID- 29341598
TI  - A Joint Strategy To Evaluate the Microscopic Origin of the Second-Harmonic
      Generation Response in Nonpolar ABCO3F Compounds.
AB  - In this paper, a joint strategy was proposed to investigate the microscopic
      origin of the second-harmonic-generation (SHG) response in nonpolar ABCO3F
      compounds. The SHG coefficients of ABCO3F were evaluated using finite-field and
      sum-over-states methods. The tendency of the obtained SHG tensors is in good
      agreement with the powder SHG response. The atomic contribution was investigated
      using variation of the atomic charges and bandwidth of occupied atomic states.
      The results show that oxygen states play a key role in determining the SHG
      response, and the neighboring divalent cations exert a indirect influence via
      covalent interaction. The bidentate bonding pattern is beneficial to obtaining a
      largely enhanced SHG response.

PMID- 29341599
TI  - Ni-Catalyzed Carbon-Carbon Bond-Forming Reductive Amination.
AB  - This report describes a three-component, Ni-catalyzed reductive coupling that
      enables the convergent synthesis of tertiary benzhydryl amines, which are
      challenging to access by traditional reductive amination methodologies. The
      reaction makes use of iminium ions generated in situ from the condensation of
      secondary N-trimethylsilyl amines with benzaldehydes, and these species undergo
      reaction with several distinct classes of organic electrophiles. The synthetic
      value of this process is demonstrated by a single-step synthesis of antimigraine
      drug flunarizine (Sibelium) and high yielding derivatization of paroxetine
      (Paxil) and metoprolol (Lopressor). Mechanistic investigations support a
      sequential oxidative addition mechanism rather than a pathway proceeding via
      alpha-amino radical formation. Accordingly, application of catalytic conditions
      to an intramolecular reductive coupling is demonstrated for the synthesis of endo
      and exocyclic benzhydryl amines.

PMID- 29341600
TI  - Combination of Heparin Binding Peptide and Heparin Cell Surface Coatings for
      Mesenchymal Stem Cell Spheroid Assembly.
AB  - Microtissues containing multiple cell types have been used in both in vitro
      models and in vivo tissue repair applications. However, to improve throughput,
      there is a need to develop a platform that supports self-assembly of a large
      number of 3D microtissues containing multiple cell types in a dynamic suspension
      system. Thus, the objective of this study was to exploit the binding interaction
      between the negatively charged glycosaminoglycan, heparin, and a known heparin
      binding peptide to establish a method that promotes assembly of mesenchymal stem
      cell (MSC) spheroids into larger aggregates. We characterized heparin binding
      peptide (HEPpep) and heparin coatings on cell surfaces and determined the
      specificity of these coatings in promoting assembly of MSC spheroids in dynamic
      culture. Overall, combining spheroids with both coatings promoted up to 70 +/-
      11% of spheroids to assemble into multiaggregate structures, as compared to only
      10 +/- 4% assembly when cells having the heparin coating were cultured with cells
      coated with a scrambled peptide. These results suggest that this self-assembly
      method represents an exciting approach that may be applicable for a wide range of
      applications in which cell aggregation is desired.

PMID- 29341601
TI  - Determining Double Bond Position in Lipids Using Online Ozonolysis Coupled to
      Liquid Chromatography and Ion Mobility-Mass Spectrometry.
AB  - The increasing focus on lipid metabolism has revealed a need for analytical
      techniques capable of structurally characterizing lipids with a high degree of
      specificity. Lipids can exist as any one of a large number of double bond
      positional isomers, which are indistinguishable by single-stage mass spectrometry
      alone. Ozonolysis reactions coupled to mass spectrometry have previously been
      demonstrated as a means for localizing double bonds in unsaturated lipids. Here
      we describe an online, solution-phase reactor using ozone produced via a low
      pressure mercury lamp, which generates aldehyde products diagnostic of cleavage
      at a particular double bond position. This flow-cell device is utilized in
      conjunction with structurally selective ion mobility-mass spectrometry. The lamp
      mediated reaction was found to be effective for multiple lipid species in both
      positive and negative ionization modes, and the conversion efficiency from
      precursor to product ions was tunable across a wide range (20-95%) by varying the
      flow rate through the ozonolysis device. Ion mobility separation of the
      ozonolysis products generated additional structural information and revealed the
      presence of saturated species in a complex mixture. The method presented here is
      simple, robust, and readily coupled to existing instrument platforms with minimal
      modifications necessary. For these reasons, application to standard lipidomic
      workflows is possible and aids in more comprehensive structural characterization
      of a myriad of lipid species.

PMID- 29341602
TI  - Polybrominated Diphenyl Ethers, Polychlorinated Biphenyls, and 2,2-Bis(4
      chlorophenyl)-1,1-dichloroethene in 7- and 9-Year-Old Children and Their Mothers
      in the Center for the Health Assessment of Mothers and Children of Salinas
      Cohort.
AB  - We report longitudinal serum concentrations of select persistent organic
      pollutants (POPs) in children at ages 7 and 9 years and in their mothers
      prenatally and again when the children were 9 years old. The participating
      families were enrolled in the Center for the Health Assessment of Mothers and
      Children of Salinas (CHAMACOS), a longitudinal birth cohort study of low-income
      Hispanic families residing in the Salinas Valley, California. We observed
      decreasing concentrations in the mothers with year of serum collection (2009 vs
      2011) for six out of seven polybrominated diphenyl ether (PBDE) congeners and for
      2,2',4,4',5-pentachlorobiphenyl (CB-99; p < 0.05). The 9-year-old children had
      similarly decreasing serum concentrations of all seven PBDE congeners, CB-99, and
      2,2',3,4,4',5'- and 2,3,3',4,4',6-hexachlorobiphenyl (CB-138/158) with year of
      serum collection (2009 vs 2011; p < 0.05). In mixed effect models accounting for
      weight gain as the children aged from 7 to 9 years, we observed an annual
      decrease (-8.3% to -13.4%) in tri- to hexaBDE concentrations (p < 0.001), except
      for 2,2',3,4,4'-tetrabromodiphenyl ether (BDE-85) and 2,2',4,4',5,5'
      hexabromodiphenyl ether (BDE-153). The concentrations of these congeners were not
      associated with time of serum collection and instead showed an -0.9% to -2.6%
      decrease per kilogram of weight gain during the study period (p < 0.05). In the
      case of tetra- to heptachlorobiphenyls, we observed -0.5% to -0.7% decrease in
      serum concentration per kilogram of weight gain (p < 0.05) and -3.0% to -3.7%
      decrease in serum concentration per year of aging (p < 0.05), except for
      2,3',4,4',5-pentachlorobiphenyl (CB-118) and 2,2',4,4',5,5'-hexachlorobiphenyl
      (CB-153), which were not associated with time of serum draw. 2,2-Bis(4
      chlorophenyl)-1,1-dichloroethene (p,p'-DDE) decreased -2.4%/kg of weight gain
      between the two sampling points (p < 0.001). These findings suggest that as
      children grow, dilution in a larger body size plays an important role in
      explaining reductions in body burden in the case of traditional POPs such as PCBs
      and p,p'-DDE. By contrast, in the case of PBDEs, reductions are likely explained
      by reduction in exposure, as illustrated by decreased concentrations in more
      recent years, possibly amplified by presumed shorter biological half-life than
      other POPs.

PMID- 29341603
TI  - PokMT1 from the Polyketomycin Biosynthetic Machinery of Streptomyces
      diastatochromogenes Tu6028 Belongs to the Emerging Family of C-Methyltransferases
      That Act on CoA-Activated Aromatic Substrates.
AB  - Recent biochemical characterizations of the MdpB2 CoA ligase and MdpB1 C
      methyltransferase (C-MT) from the maduropeptin (MDP, 2) biosynthetic machinery
      revealed unusual pathway logic involving C-methylation occurring on a CoA
      activated aromatic substrate. Here we confirmed this pathway logic for the
      biosynthesis of polyketomycin (POK, 3). Biochemical characterization
      unambiguously established that PokM3 and PokMT1 catalyze the sequential
      conversion of 6-methylsalicylic acid (6-MSA, 4) to form 3,6-dimethylsalicylyl-CoA
      (3,6-DMSA-CoA, 6), which serves as the direct precursor for the 3,6
      dimethylsalicylic acid (3,6-DMSA) moiety in the biosynthesis of 3. PokMT1
      catalyzes the C-methylation of 6-methylsalicylyl-CoA (6-MSA-CoA, 5) with a kcat
      of 1.9 min-1 and a Km of 2.2 +/- 0.1 MUM, representing the most proficient C-MT
      characterized to date. Bioinformatics analysis of MTs from natural product
      biosynthetic machineries demonstrated that PokMT1 and MdpB1 belong to a
      phylogenetic clade of C-MTs that preferably act on aromatic acids. Significantly,
      this clade includes the structurally characterized enzyme SibL, which catalyzes C
      methylation of 3-hydroxykynurenine in its free acid form, using two conserved
      tyrosine residues for catalysis. A homology model and site-directed mutagenesis
      suggested that PokMT1 also employs this unusual arrangement of tyrosine residues
      to coordinate C-methylation but revealed a large cavity capable of accommodating
      the CoA moiety tethered to 5. CoA activation of the aromatic acid substrate may
      represent a general strategy that could be exploited to improve catalytic
      efficiency. This study sets the stage to further investigate and exploit the
      catalytic utility of this emerging family of C-MTs in biocatalysis and synthetic
      biology.

PMID- 29341604
TI  - Ce3+-Doping to Modulate Photoluminescence Kinetics for Efficient CsPbBr3
      Nanocrystals Based Light-Emitting Diodes.
AB  - Inorganic perovskite CsPbBr3 nanocrystals (NCs) are emerging, highly attractive
      light emitters with high color purity and good thermal stability for light
      emitting diodes (LEDs). Their high photo/electroluminescence efficiencies are
      very important for fabricating efficient LEDs. Here, we propose a novel strategy
      to enhance the photo/electroluminescence efficiency of CsPbBr3 NCs through doping
      of heterovalent Ce3+ ions via a facile hot-injection method. The Ce3+ cation was
      chosen as the dopant for CsPbBr3 NCs by virtue of its similar ion radius and
      formation of higher energy level of conduction band with bromine in comparison
      with the Pb2+ cation to maintain the integrity of perovskite structure without
      introducing additional trap states. It was found that by increasing the doping
      amount of Ce3+ in CsPbBr3 NCs to 2.88% (atomic percentage of Ce compared to Pb)
      the photoluminescence quantum yield (PLQY) of CsPbBr3 NCs reached up to 89%, a
      factor of 2 increase in comparison with the native, undoped ones. The ultrafast
      transient absorption and time-resolved photoluminescence (PL) spectroscopy
      revealed that Ce3+-doping can significantly modulate the PL kinetics to enhance
      the PL efficiency of doped CsPbBr3 NCs. As a result, the LED device fabricated by
      adopting Ce3+-doped CsPbBr3 NCs as the emitting layers exhibited a pronounced
      improvement of electroluminescence with external quantum efficiency (EQE) from
      1.6 to 4.4% via Ce3+-doping.

PMID- 29341605
TI  - Prediction of Active Site and Distal Residues in E. coli DNA Polymerase III alpha
      Polymerase Activity.
AB  - The process of DNA replication is carried out with high efficiency and accuracy
      by DNA polymerases. The replicative polymerase in E. coli is DNA Pol III, which
      is a complex of 10 different subunits that coordinates simultaneous replication
      on the leading and lagging strands. The 1160-residue Pol III alpha subunit is
      responsible for the polymerase activity and copies DNA accurately, making one
      error per 105 nucleotide incorporations. The goal of this research is to
      determine the residues that contribute to the activity of the polymerase subunit.
      Homology modeling and the computational methods of THEMATICS and POOL were used
      to predict functionally important amino acid residues through their computed
      chemical properties. Site-directed mutagenesis and biochemical assays were used
      to validate these predictions. Primer extension, steady-state single-nucleotide
      incorporation kinetics, and thermal denaturation assays were performed to
      understand the contribution of these residues to the function of the polymerase.
      This work shows that the top 15 residues predicted by POOL, a set that includes
      the three previously known catalytic aspartate residues, seven remote residues,
      plus five previously unexplored first-layer residues, are important for function.
      Six previously unidentified residues, R362, D405, K553, Y686, E688, and H760, are
      each essential to Pol III activity; three additional residues, Y340, R390, and
      K758, play important roles in activity.

PMID- 29341606
TI  - Human Oxoguanine Glycosylase 1 Removes Solution Accessible 8-Oxo-7,8
      dihydroguanine Lesions from Globally Substituted Nucleosomes Except in the Dyad
      Region.
AB  - Persistent DNA damage is responsible for mutagenesis, aging, and disease. Repair
      of the prototypic oxidatively damaged guanine lesion 8-oxo-7,8-dihydroguanine (8
      oxoG) is initiated by oxoguanine glycosylase (hOGG1 in humans). In this work, we
      examine hOGG1 activity on DNA packaged as it is in chromatin, in a nucleosome
      core particle (NCP). We use synthetic methods to generate a population of NCPs
      with G to 8-oxoG substitutions and evaluate the global profile of hOGG1 repair in
      packaged DNA. For several turns of the helix, we observe that solution accessible
      8-oxoGs are sites of activity for hOGG1. At the dyad axis, however, hOGG1
      activity is suppressed, even at lesions predicted to be solution accessible by
      hydroxyl radical footprinting (HRF). We predict this diminished activity is due
      to the properties of the DNA unique to the dyad axis and/or the local histone
      environment. In contrast to the dyad axis, the DNA ends reveal hOGG1 activity at
      sites predicted by HRF to be both solution accessible and inaccessible. We
      attribute the lack of correlation between hOGG1 activity and solution
      accessibility at the ends of the DNA to transient unwrapping of the DNA from the
      protein core, thus exposing the inward-facing lesions.

PMID- 29341607
TI  - In Vitro Pharmacokinetic Optimizations of AM2-S31N Channel Blockers Led to the
      Discovery of Slow-Binding Inhibitors with Potent Antiviral Activity against Drug
      Resistant Influenza A Viruses.
AB  - Influenza viruses are respiratory pathogens that are responsible for both
      seasonal influenza epidemics and occasional influenza pandemics. The narrow
      therapeutic window of oseltamivir, coupled with the emergence of drug resistance,
      calls for the next-generation of antivirals. With our continuous interest in
      developing AM2-S31N inhibitors as oral influenza antivirals, we report here the
      progress of optimizing the in vitro pharmacokinetic (PK) properties of AM2-S31N
      inhibitors. Several AM2-S31N inhibitors, including compound 10b, were discovered
      to have potent channel blockage, single to submicromolar antiviral activity, and
      favorable in vitro PK properties. The antiviral efficacy of compound 10b was also
      synergistic with oseltamivir carboxylate. Interestingly, binding kinetic studies
      (Kd, Kon, and Koff) revealed several AM2-S31N inhibitors that have similar Kd
      values but significantly different Kon and Koff values. Overall, this study
      identified a potent lead compound (10b) with improved in vitro PK properties that
      is suitable for the in vivo mouse model studies.

PMID- 29341608
TI  - Molecular Dynamics Pinpoint the Global Fluorine Effect in Balanoid Binding to
      PKCepsilon and PKA.
AB  - (-)-Balanol is an adenosine triphosphate mimic that inhibits protein kinase C
      (PKC) isozymes and cAMP-dependent protein kinase (PKA) with limited selectivity.
      While PKA is known as a tumor promoter, PKC isozymes can be tumor promoters or
      suppressors. In particular, PKCepsilon is frequently involved in tumorigenesis
      and a potential target for anticancer drugs. We recently reported that
      stereospecific fluorination of balanol yielded a balanoid with enhanced
      selectivity for PKCepsilon over other PKC isozymes and PKA, although the global
      fluorine effect behind the selectivity enhancement is not fully understood.
      Interestingly, in contrast to PKA, PKCepsilon is more sensitive to this fluorine
      effect. Here we investigate the global fluorine effect on the different binding
      responses of PKCepsilon and PKA to balanoids using molecular dynamics (MD)
      simulations. For the first time to the best of our knowledge, we found that a
      structurally equivalent residue in each kinase, Thr184 in PKA and Ala549 in
      PKCepsilon, is essential for the different binding responses. Furthermore, the
      study revealed that the invariant Lys, Lys73 in PKA and Lys437 in PKCepsilon,
      already known to have a crucial role in the catalytic activity of kinases, serves
      as the main anchor for balanol binding. Overall, while Thr184 in PKA attenuates
      the effect of fluorination, Ala549 permits remote response of PKCepsilon to
      fluorine substitution, with implications for rational design of future balanol
      based PKCepsilon inhibitors.

PMID- 29341609
TI  - Probing and Quantifying the Food-Borne Pathogens and Toxins: From In Vitro to In
      Vivo.
AB  - Development of real-time and in situ analytical methods for determination of food
      borne pathogens and toxins ingested into the human body would be a promising
      research direction in the food-safety area. The present perspective starts with
      summarization of the up-to-date progress of the nanomaterial-assisted in vitro
      detection methods for pathogens and toxins and finally focuses on application of
      animal bioimaging to in vivo study, including prospective strategies for in vivo
      quantification of target pathogens or toxins and in vivo investigation of their
      behaviors inside the living body, with the assistance of real-time and non
      invasive optical bioimaging. This perspective provides the advisory direction for
      food-safety research, from in vitro to in vivo, along with a prospective
      discussion of the further development roadmap of the food-safety detection
      techniques, especially the bioimaging-guided methods for investigation and
      mediation of the food contamination effect to human health.

PMID- 29341610
TI  - Visible-Light-Mediated Ipso-Carboacylation of Alkynes: Synthesis of 3
      Acylspiro[4,5]trienones from N-(p-Methoxyaryl)propiolamides and Acyl Chlorides.
AB  - A novel visible-light-mediated ipso-carboacylation of N-(p
      methoxyaryl)propiolamides with acyl chloride has been established for the
      synthesis of diverse 3-acylspiro[4,5]trienones with high selectivity and
      efficiency. This method represents a new difunctionalization of alkynes through
      cross coupling of the acyl chloride C-Cl bonds with an ipso-aromatic carbon by
      simultaneously forming two new carbon-carbon bonds and one carbon-oxygen double
      bond.

PMID- 29341611
TI  - Moving Boundary Truncated Grid Method for Wave Packet Dynamics.
AB  - The moving boundary truncated grid method is developed to significantly reduce
      the number of grid points required for wave packet propagation. The time
      dependent Schrodinger equation (TDSE) and the imaginary time Schrodinger equation
      (ITSE) are integrated using an adaptive algorithm which economizes the number of
      grid points. This method employs a variable number of grid points in the Eulerian
      frame (grid points fixed in space) and adaptively defines the boundaries of the
      truncated grid. The truncated grid method is first applied to the time
      integration of the TDSE for the photodissociation dynamics of NOCl and a three
      dimensional quantum barrier scattering problem. The time-dependent truncated grid
      precisely captures the wave packet evolution for the photodissociation of NOCl
      and finely adjusts according to the process of the wave packet bifurcation into
      reflected and transmitted components for the barrier scattering problem. The
      truncated grid method is also applied to the time integration of the ITSE for the
      eigenstates of quantum systems. Compared to the full grid calculations, the
      truncated grid method requires fewer grid points to achieve high accuracy for the
      stationary state energies and wave functions for a two-dimensional double well
      potential and the Ar trimer. Therefore, the truncated grid method demonstrates a
      significant reduction in the number of grid points needed to perform accurate
      wave packet propagation governed by the TDSE or the ITSE.

PMID- 29341612
TI  - Stabilization of NaBH4 in Methanol Using a Catalytic Amount of NaOMe. Reduction
      of Esters and Lactones at Room Temperature without Solvent-Induced Loss of
      Hydride.
AB  - Rapid reaction of NaBH4 with MeOH precludes its use as a solvent for large-scale
      ester reductions. We have now learned that a catalytic amount of NaOMe (5 mol %)
      stabilizes NaBH4 solutions in methanol at 25  degrees C and permits the use of
      these solutions for the reduction of esters to alcohols. The generality of this
      reduction method was demonstrated using 22 esters including esters of naturally
      occurring chiral gamma-butyrolactone containing dicarboxylic acids. This method
      permits the chemoselective reductions of esters in the presence of cyano and
      nitro groups and the reductive cyclization of a pyrrolidinedione ester to a fused
      five-membered furo[2,3-b]pyrrole and a (-)-crispine A analogue in high optical
      and chemical yields. Lactones, aliphatic esters, aromatic esters containing
      electron-withdrawing groups, and heteroaryl esters are reduced more rapidly than
      aryl esters containing electron-donating groups. The 11B NMR spectrum of the
      NaOMe-stabilized NaBH4 solutions showed a minor quartet  due to
      monomethoxyborohydride (NaBH3OMe) that persisted up to 18 h at 25  degrees C. We
      postulate that NaBH3OMe is probably the active reducing agent. In support of this
      hypothesis, the activation barrier for hydride transfer from BH3(OMe)- onto
      benzoic acid methyl ester was calculated as 18.3 kcal/mol.

PMID- 29341613
TI  - What Gives an Insulin Hexamer Its Unique Shape and Stability? Role of Ten
      Confined Water Molecules.
AB  - Self-assembly of proteins often gives rise to interesting quasi-stable structures
      that serve important biological purposes. Insulin hexamer is such an assembly.
      While monomer is the biologically active form of insulin, hexamer serves as the
      storehouse of the hormone. The hexamer also prevents the formation of higher
      order aggregates. While several studies explored the role of bivalent metal ions
      like Zn2+, Ca2+, etc., in the stabilization of the hexameric form, the role of
      water molecules has been ignored. We combine molecular dynamics simulations,
      quantum calculations, and X-ray analyses to discover that a team of approximately
      10 water molecules confined inside a barrel-shaped nanocavity at the center of
      insulin hexamer is one of the major causes that account for the unusual stability
      of the biomolecular assembly. These cavity water molecules exhibit interesting
      dynamical features like intermittent escape and reentrance. We find that these
      water molecules are dynamically slower than the bulk and weave an intricate
      hydrogen bond network among themselves and with neighboring protein residues to
      generate a robust backbone at the center of the hexamer that holds the
      association strongly from inside and maintains the barrel shape.

PMID- 29341614
TI  - Synthesis of Quinazolines via an Iron-Catalyzed Oxidative Amination of N-H
      Ketimines.
AB  - An efficient synthesis of quinazolines based on an iron-catalyzed C(sp3)-H
      oxidation and intramolecular C-N bond formation using tert-BuOOH as the terminal
      oxidant is described. The reaction of readily available 2-alkylamino
      benzonitriles with various organometallic reagents led to 2-alkylamino N-H
      ketimine species. The FeCl2-catalyzed C(sp3)-H oxidation of the alkyl group
      employing tert-BuOOH followed by intramolecular C-N bond formation and
      aromatization afforded a wide variety of 2,4-disubstituted quinazolines in good
      to excellent yields.

PMID- 29341615
TI  - Merely Measuring the UV-Visible Spectrum of Gold Nanoparticles Can Change Their
      Charge State.
AB  - Metallic nanostructures exhibit a strong plasmon resonance at a wavelength whose
      value is sensitive to the charge density in the nanostructure, its size, shape,
      interparticle coupling, and the dielectric properties of its surrounding medium.
      Here we use UV-visible transmission and reflectance spectroscopy to track the
      shifts of the plasmon resonance in an array of gold nanoparticles buried under
      metal-oxide layers of varying thickness produced using atomic layer deposition
      (ALD) and then coated with bulk layers of one of three metals: aluminum, silver,
      or gold. A significant shift in the plasmon resonance was observed and a precise
      value of omegap, the plasmon frequency of the gold comprising the nanoparticles,
      was determined by modeling the composite of gold nanoparticles and metal-oxide
      layer as an optically homogeneous film of core-shell particles bounded by two
      substrates: one of quartz and the other being one of the aforementioned metals,
      then using a Maxwell-Garnett effective medium expression to extract omegap for
      the gold nanoparticles before and after coating with the bulk metals. Under
      illumination, the change in the charge density of the gold nanoparticles per
      particle determined from the change in the values of omegap is found to be some
      50-fold greater than what traditional electrostatic contact electrification
      models compute based on the work function difference of the two conductive
      materials. Moreover, when using bulk gold as the capping layer, which should have
      resulted in a negligible charge exchange between the gold nanoparticles and the
      bulk gold, a significant charge transfer from the bulk gold layer to the
      nanoparticles was observed as with the other metals. We explain these
      observations in terms of the "plasmoelectric effect", recently described by
      Atwater and co-workers, in which the gold nanoparticles modify their charge
      density to allow their resonant wavelength to match that of the incident light,
      thereby achieving, a lower value of the chemical potential due to the entropy
      increase resulting from the conversion of the plasmon's energy to heat. We
      conclude that even the act of registering the spectrum of nanoparticles is at
      times sufficient to alter their charge densities and hence their UV-visible
      spectra.

PMID- 29341616
TI  - Stochasticity of Pores Interconnectivity in Li-O2 Batteries and its Impact on the
      Variations in Electrochemical Performance.
AB  - While large dispersions in electrochemical performance have been reported for
      lithium oxygen batteries in the literature, they have not been investigated in
      any depth. The variability in the results is often assumed to arise from
      differences in cell design, electrode structure, handling and cell preparation at
      different times. An accurate theoretical framework turns out to be needed to get
      a better insight into the mechanisms underneath and to interpret experimental
      results. Here, we develop and use a pore network model to simulate the
      electrochemical performance of three-dimensionally resolved lithium-oxygen
      cathode mesostructures obtained from TXM nanocomputed tomography. We apply this
      model to the 3D reconstructed object of a Super P carbon electrode and calculate
      discharge curves, using identical conditions, for four different zones in the
      electrode and their reversed configurations. The resulting galvanostatic
      discharge curves show some dispersion, (both in terms of capacity and
      overpotential) which we attribute to the way pores are connected with each other.
      Based on these results, we propose that the stochastic nature of pores
      interconnectivity and the microscopic arrangement of pores can lead, at least
      partially, to the variations in electrochemical results observed experimentally.

PMID- 29341618
TI  - Reactions of 1,5-Diaryl-3-(trifluoromethyl)pent-1-en-4-yn-3-yl Cations with
      Benzene in TfOH. Synthesis of CF3-"Helicopter"-Like Molecules.
AB  - Trimethylsilyl ethers of 1,5-diaryl-3-(trifluoromethyl)pent-1-en-4-yn-3-oles in
      superacid CF3SO3H (TfOH) give rise to the corresponding intermediate CF3
      pentenynyl cations. These species react with benzene to afford conjugated CF3
      pentenynes, which undergo subsequent cyclization, first, into CF3
      cycloheptadienes and, finally, into unusual CF3-"helicopter"-like bicyclic
      structures.

PMID- 29341617
TI  - Enhancing Docetaxel Delivery to Multidrug-Resistant Cancer Cells with Albumin
      Coated Nanocrystals.
AB  - Intravenous delivery of poorly water-soluble anticancer drugs such as docetaxel
      (DTX) is challenging due to the low bioavailability and the toxicity related to
      solubilizing excipients. Colloidal nanoparticles are used as alternative
      carriers, but low drug loading capacity and circulation instability limit their
      clinical translation. To address these challenges, DTX nanocrystals (NCs) were
      prepared using Pluronic F127 as an intermediate stabilizer and albumin as a
      functional surface modifier, which were previously found to be effective in
      producing small and stable NCs. We hypothesize that the albumin-coated DTX NCs
      (DTX-F-alb) will remain stable in serum-containing medium so as to effectively
      leverage the enhanced permeability and retention effect. In addition, the surface
      bound albumin, in its native form, may contribute to cellular transport of NCs
      through interactions with albumin-binding proteins such as secreted protein
      acidic and rich in cysteine (SPARC). DTX-F-alb NCs showed sheet-like structure
      with an average length, width, and thickness of 284 +/- 96, 173 +/- 56, and 40 +/
      8 nm and remained stable in 50% serum solution at a concentration greater than
      10 MUg/mL. Cytotoxicity and cellular uptake of DTX-F-alb and unformulated (free)
      DTX were compared on three cell lines with different levels of SPARC expression
      and DTX sensitivity. While the uptake of free DTX was highly dependent on DTX
      sensitivity, DTX-F-alb treatment resulted in relatively consistent cellular
      levels of DTX. Free DTX was more efficient in entering drug-sensitive B16F10 and
      SKOV-3 cells than DTX-F-alb, with consistent cytotoxic effects. In contrast,
      multidrug-resistant NCI/ADR-RES cells took up DTX-F-alb more than free DTX with
      time and responded better to the former. This difference was reduced by SPARC
      knockdown. The high SPARC expression level of NCI/ADR-RES cells, the known
      affinity of albumin for SPARC, and the opposing effect of SPARC knockdown support
      that DTX-F-alb have exploited the surface-bound albumin-SPARC interaction in
      entering NCI/ADR-RES cells. Albumin-coated NC system is a promising formulation
      for the delivery of hydrophobic anticancer drugs to multidrug-resistant tumors.

PMID- 29341619
TI  - New Folate-Grafted Chitosan Derivative To Improve Delivery of Paclitaxel-Loaded
      Solid Lipid Nanoparticles for Lung Tumor Therapy by Inhalation.
AB  - Inhaled chemotherapy for the treatment of lung tumors requires that drug delivery
      systems improve selectivity for cancer cells and tumor penetration and allow
      sufficient lung residence. To this end, we developed solid lipid nanoparticles
      (SLN) with modified surface properties. We successfully synthesized a new folate
      grafted copolymer of polyethylene glycol (PEG) and chitosan, F-PEG-HTCC, with a
      PEG-graft ratio of 7% and a molecular weight range of 211-250 kDa. F-PEG-HTCC
      coated, paclitaxel-loaded SLN were prepared with an encapsulation efficiency,
      mean diameter, and zeta potential of about 100%, 250 nm, and +32 mV,
      respectively. The coated SLN entered folate receptor (FR)-expressing HeLa and
      M109-HiFR cells in vitro and M109 tumors in vivo after pulmonary delivery. The
      coated SLN significantly decreased the in vitro half-maximum inhibitory
      concentrations of paclitaxel in M109-HiFR cells (60 vs 340 nM, respectively). We
      demonstrated that FR was involved in these improvements, especially in M109-HiFR
      cells. After pulmonary delivery in vivo, the coated SLN had a favorable
      pharmacokinetic profile, with pulmonary exposure to paclitaxel prolonged to up to
      6 h and limited systemic distribution. Our preclinical findings therefore
      demonstrated the positive impact of the coated SLN on the delivery of paclitaxel
      by inhalation.

PMID- 29341620
TI  - Hedychins A and B, 6,7-Dinorlabdane Diterpenoids with a Peroxide Bridge from
      Hedychium forrestii.
AB  - Hedychins A (1) and B (2), two unprecedented 6,7-dinorlabdane ditepenoids with a
      peroxide bridge, were obtained from the rhizomes of Hedychium forrestii. Their
      structures and absolute configurations were unequivocally established by a
      combination of spectroscopic data and X-ray single-crystal diffractions. Their
      plausible biosynthetic pathway was proposed. Compound 2 exhibited cytotoxicity
      against HepG2 and XWLC-05 cell lines with IC50 values of 8.0 and 19.7 MUM,
      respectively.

PMID- 29341621
TI  - Sustainable HandaPhos-ppm Palladium Technology for Copper-Free Sonogashira
      Couplings in Water under Mild Conditions.
AB  - Complexation of ca. 1000 ppm Pd(OAc)2 with the ligand HandaPhos (1-1.5:1) leads
      to a precatalyst that efficiently mediates Sonogashira couplings in aqueous
      nanomicelles under very mild conditions. Neither copper nor organic solvent is
      required in the reaction medium, and the product can be isolated directly from
      the reaction flask, leaving behind a reaction mixture that can be recycled
      without additional additives.

PMID- 29341622
TI  - Cyclic Peptoids as Topological Templates: Synthesis via Central to Conformational
      Chirality Induction.
AB  - Chiral induction was utilized for the synthesis of diastereopure cyclic peptoids
      containing an N-benzyl alanine residue. Molecular modeling, NMR spectroscopy,
      single-crystal X-ray diffraction studies, and HPLC with chiral stationary phase
      demonstrated easy formation of free and sodium/benzylammonium complexed cyclic
      oligomers through strategic incorporation of a single stereogenic center in the
      oligomeric backbone. The synthesis of cyclic peptoids with defined conformational
      chirality and appropriate side chain topology is now possible.

PMID- 29341623
TI  - Is Subsurface Oxygen Necessary for the Electrochemical Reduction of CO2 on
      Copper?
AB  - It has recently been proposed that subsurface oxygen is crucial for the
      adsorption and subsequent electroreduction of CO2 on copper. Using density
      functional theory, we have studied the stability and diffusion of subsurface
      oxygen in single crystals of copper exposing (111) and (100) facets. Oxygen is at
      least 1.5 eV more stable on the surface than beneath it for both crystal
      orientations; interstitial sites are too small to accommodate oxygen. The rate of
      atomic oxygen diffusion from one layer below a Cu(111) surface to the surface is
      5 * 103 s-1. Oxygen can survive longer in deeper layers, but it does not promote
      CO2 adsorption there. Diffusion of subsurface oxygen is easier to the less-dense
      Cu(100) surface, even from lower layers (rate ~ 1 * 107 s-1). Once the applied
      voltage and dispersion forces are properly modeled, we find that subsurface
      oxygen is unnecessary for CO2 adsorption on copper.

PMID- 29341624
TI  - Regio and Enantioselective Organocatalytic Friedel-Crafts Alkylation of 4
      Aminoindoles at the C7-Position.
AB  - A chiral phosphoric acid catalyzed highly regio- and enantioselective Friedel
      Crafts alkylation at the indole C7-position was developed via the introduction of
      an alkylamine moiety at the C4-position of the indole ring. The methodology is
      applicable to a wide range of 4-aminoindoles and beta,gamma-unsaturated alpha
      ketimino esters to furnish the corresponding C7-position functionalized chiral
      indole derivatives in high yields with moderate to excellent
      enantioselectivities. Furthermore, the alpha-ketimino ester moiety in the
      products is a versatile building block and enables many further transformations.

PMID- 29341625
TI  - Biomimetic Total Syntheses of Callistrilones A, B, and D.
AB  - A biomimetic total syntheses of antibacterial natural products (+/-)
      callistrilones A, B, and D, the first triketone-phloroglucinol-monoterpene
      hybrids with an unprecedented [1]benzofuro[2,3-a]xanthene and [1]benzofuro[3,2
      b]xanthene pentacyclic ring system along with the postulated biosynthetic
      intermediate, isolated from the leaves of Callistemon rigidus, were achieved. The
      total synthesis features highly regio- and diastereoselective catalytic Friedel
      Crafts alkylation, palladium-catalyzed Wacker-type oxidative cyclization, Michael
      addition, and late-stage diastereoselective epoxide formation from the extremely
      hindered beta face as key steps.

PMID- 29341626
TI  - Hierarchically Patterned Noncovalent Functionalization of 2D Materials by
      Controlled Langmuir-Schaefer Conversion.
AB  - Noncovalent monolayer chemistries are often used to functionalize 2D materials.
      Nanoscopic ligand ordering has been widely demonstrated (e.g., lying-down
      lamellar phases of functional alkanes); however, combining this control with
      micro- and macroscopic patterning for practical applications remains a
      significant challenge. A few reports have demonstrated that standing phase
      Langmuir films on water can be converted into nanoscopic lying-down molecular
      domains on 2D substrates (e.g., graphite), using horizontal dipping (Langmuir
      Schaefer, LS, transfer). Molecular patterns are known to form at scales up to
      millimeters in Langmuir films, suggesting the possibility of transforming such
      structures into functional patterns on 2D materials. However, to our knowledge,
      this approach has not been investigated, and the rules governing LS conversion
      are not well understood. In part, this is because the conversion process is
      mechanistically very different from classic LS transfer of standing phases;
      challenges also arise due to the need to characterize structure in noncovalently
      adsorbed ligand layers <0.5 nm thick, at scales ranging from millimeters to
      nanometers. Here, we show that scanning electron microscopy enables diynoic acid
      lying-down phases to be imaged across this range of scales; using this structural
      information, we establish conditions for LS conversion to create hierarchical
      microscopic and nanoscopic functional patterns. Such control opens the door to
      tailoring noncovalent surface chemistry of 2D materials to pattern local
      interactions with the environment.

PMID- 29341627
TI  - Ru(II)-Catalyzed Oxidative Heck-Type Olefination of Aromatic Carboxylic Acids
      with Styrenes through Carboxylate-Assisted C-H Bond Activation.
AB  - A straightforward synthesis of 2-styrylbenzoic acids from aryl carboxylic acids
      is disclosed through a carboxylate-assisted coupling under Ru(II) catalysis. This
      protocol is simple and exhibits broad scope with high tolerance of common organic
      functional groups, providing good to excellent yields of diverse olefinated
      products. The efficacy of this protocol has been showcased through sequential
      syntheses of isochromanone, isocoumarin, and formal synthesis of anacardic acid
      derivative in good yields.

PMID- 29341628
TI  - Dark Matter Coannihilation with a Lighter Species.
AB  - We propose a new thermal freeze-out mechanism for ultraheavy dark matter. Dark
      matter coannihilates with a lighter unstable species that is nearby in mass,
      leading to an annihilation rate that is exponentially enhanced relative to
      standard weakly interactive massive particles. This scenario destabilizes any
      potential dark matter candidate. In order to remain consistent with astrophysical
      observations, our proposal necessitates very long-lived states, motivating
      striking phenomenology associated with the late decays of ultraheavy dark matter,
      potentially as massive as the scale of grand unified theories, M_{GUT}~10^{16} 
      GeV.

PMID- 29341629
TI  - Mirror Charge Radii and the Neutron Equation of State.
AB  - The differences in the charge radii of mirror nuclei are shown to be proportional
      to the derivative of the neutron equation of state and the symmetry energy at
      nuclear matter saturation density. This derivative is important for constraining
      the neutron equation of state for use in astrophysics. The charge radii of
      several neutron-rich nuclei are already measured to the accuracy of about 0.005
      fm. Experiments at isotope-separator and radioactive-beam facilities are needed
      to measure the charge radii of the corresponding proton-rich mirror nuclei to a
      similar accuracy. It is also shown that neutron skins of nuclei with N=Z depend
      upon the value of the symmetry energy at a density of 0.10  nucleons/fm^{3}.

PMID- 29341630
TI  - Terahertz Sum-Frequency Excitation of a Raman-Active Phonon.
AB  - In stimulated Raman scattering, two incident optical waves induce a force
      oscillating at the difference of the two light frequencies. This process has
      enabled important applications such as the excitation and coherent control of
      phonons and magnons by femtosecond laser pulses. Here, we experimentally and
      theoretically demonstrate the so far neglected up-conversion counterpart of this
      process: THz sum-frequency excitation of a Raman-active phonon mode, which is
      tantamount to two-photon absorption by an optical transition between two adjacent
      vibrational levels. Coherent control of an optical lattice vibration of diamond
      is achieved by an intense terahertz pulse whose spectrum is centered at half the
      phonon frequency of 40 THz. Remarkably, the carrier-envelope phase of the THz
      pulse is directly transferred into the phase of the lattice vibration. New
      prospects in general infrared spectroscopy, action spectroscopy, and lattice
      trajectory control in the electronic ground state emerge.

PMID- 29341631
TI  - Rapid Transition of the Hole Rashba Effect from Strong Field Dependence to
      Saturation in Semiconductor Nanowires.
AB  - The electric field manipulation of the Rashba spin-orbit coupling effects
      provides a route to electrically control spins, constituting the foundation of
      the field of semiconductor spintronics. In general, the strength of the Rashba
      effects depends linearly on the applied electric field and is significant only
      for heavy-atom materials with large intrinsic spin-orbit interaction under high
      electric fields. Here, we illustrate in 1D semiconductor nanowires an anomalous
      field dependence of the hole (but not electron) Rashba effect (HRE). (i) At low
      fields, the strength of the HRE exhibits a steep increase with the field so that
      even low fields can be used for device switching. (ii) At higher fields, the HRE
      undergoes a rapid transition to saturation with a giant strength even for light
      atom materials such as Si (exceeding 100 meV A). (iii) The nanowire-size
      dependence of the saturation HRE is rather weak for light-atom Si, so size
      fluctuations would have a limited effect; this is a key requirement for
      scalability of Rashba-field-based spintronic devices. These three features offer
      Si nanowires as a promising platform for the realization of scalable
      complementary metal-oxide-semiconductor compatible spintronic devices.

PMID- 29341632
TI  - Polarizing Oxygen Vacancies in Insulating Metal Oxides under a High Electric
      Field.
AB  - We demonstrate a thermodynamic formulation to quantify defect formation
      energetics in an insulator under a high electric field. As a model system, we
      analyzed neutral oxygen vacancies (color centers) in alkaline-earth-metal binary
      oxides using density functional theory, Berry phase calculations, and maximally
      localized Wannier functions. The work of polarization lowers the field-dependent
      electric Gibbs energy of formation of this defect. This is attributed mainly to
      the ease of polarizing the two electrons trapped in the vacant site, and
      secondarily to the defect induced reduction in bond stiffness and softening of
      phonon modes. The formulation and analysis have implications for understanding
      the behavior of insulating oxides in electronic, magnetic, catalytic, and
      electrocaloric devices under a high electric field.

PMID- 29341633
TI  - Universal Quantum Computing with Measurement-Induced Continuous-Variable Gate
      Sequence in a Loop-Based Architecture.
AB  - We propose a scalable scheme for optical quantum computing using measurement
      induced continuous-variable quantum gates in a loop-based architecture. Here,
      time-bin-encoded quantum information in a single spatial mode is
      deterministically processed in a nested loop by an electrically programmable gate
      sequence. This architecture can process any input state and an arbitrary number
      of modes with almost minimum resources, and offers a universal gate set for both
      qubits and continuous variables. Furthermore, quantum computing can be performed
      fault tolerantly by a known scheme for encoding a qubit in an infinite
      dimensional Hilbert space of a single light mode.

PMID- 29341634
TI  - Publisher's Note: Ultimate Precision of Adaptive Noise Estimation [Phys. Rev.
      Lett. 118, 100502 (2017)].
AB  - This corrects the article DOI: 10.1103/PhysRevLett.118.100502.

PMID- 29341635
TI  - Low-Field-Triggered Large Magnetostriction in Iron-Palladium Strain Glass Alloys.
AB  - Development of miniaturized magnetostriction-associated devices requires low
      field-triggered large magnetostriction. In this study, we acquired a large
      magnetostriction (800 ppm) triggered by a low saturation field (0.8 kOe) in iron
      palladium (Fe-Pd) alloys. Magnetostriction enhancement jumping from 340 to 800
      ppm was obtained with a slight increase in Pd concentration from 31.3 to 32.3 at.
      %. Further analysis showed that such a slight increase led to suppression of the
      long-range ordered martensitic phase and resulted in a frozen short-range ordered
      strain glass state. This strain glass state possessed a two-phase nanostructure
      with nanosized frozen strain domains embedded in the austenite matrix, which was
      responsible for the unique magnetostriction behavior. Our study provides a way to
      design novel magnetostrictive materials with low-field-triggered large
      magnetostriction.

PMID- 29341636
TI  - Pair Potential with Submillikelvin Uncertainties and Nonadiabatic Treatment of
      the Halo State of the Helium Dimer.
AB  - The pair potential for helium is computed with accuracy improved by an order of
      magnitude relative to the best previous determination. For the well region, its
      uncertainties are now below 1 millikelvin. The main improvement is due to the use
      of explicitly correlated wave functions at the nonrelativistic Born-Oppenheimer
      (BO) level of theory. The diagonal BO and the relativistic corrections are
      obtained from large full configuration interaction calculations. Nonadiabatic
      perturbation theory is used to predict the properties of the halo state of the
      helium dimer. Its binding energy and the average value of the interatomic
      distance are found to be 138.9(5) neV and 47.13(8) A. The binding energy agrees
      with its first experimental determination of 151.9(13.3) neV [Zeller et al.,
      Proc. Natl. Acad. Sci. U.S.A. 113, 14651 (2016)PNASA60027
      842410.1073/pnas.1610688113].

PMID- 29341637
TI  - Enhancing Sideband Cooling by Feedback-Controlled Light.
AB  - We realize a phase-sensitive closed-loop control scheme to engineer the
      fluctuations of the pump field which drives an optomechanical system and show
      that the corresponding cooling dynamics can be significantly improved. In
      particular, operating in the counterintuitive "antisquashing" regime of positive
      feedback and increased field fluctuations, sideband cooling of a nanomechanical
      membrane within an optical cavity can be improved by 7.5 dB with respect to the
      case without feedback. Close to the quantum regime of reduced thermal noise, such
      feedback-controlled light would allow going well below the quantum backaction
      cooling limit.

PMID- 29341638
TI  - Quantum Communication Using Coherent Rejection Sampling.
AB  - Compression of a message up to the information it carries is key to many tasks
      involved in classical and quantum information theory. Schumacher [B. Schumacher,
      Phys. Rev. A 51, 2738 (1995)PLRAAN1050-294710.1103/PhysRevA.51.2738] provided one
      of the first quantum compression schemes and several more general schemes have
      been developed ever since [M. Horodecki, J. Oppenheim, and A. Winter, Commun.
      Math. Phys. 269, 107 (2007); CMPHAY0010-361610.1007/s00220-006-0118-xI. Devetak
      and J. Yard, Phys. Rev. Lett. 100, 230501 (2008); PRLTAO0031
      900710.1103/PhysRevLett.100.230501A. Abeyesinghe, I. Devetak, P. Hayden, and A.
      Winter, Proc. R. Soc. A 465, 2537 (2009)PRLAAZ1364-502110.1098/rspa.2009.0202].
      However, the one-shot characterization of these quantum tasks is still under
      development, and often lacks a direct connection with analogous classical tasks.
      Here we show a new technique for the compression of quantum messages with the aid
      of entanglement. We devise a new tool that we call the convex split lemma, which
      is a coherent quantum analogue of the widely used rejection sampling procedure in
      classical communication protocols. As a consequence, we exhibit new explicit
      protocols with tight communication cost for quantum state merging, quantum state
      splitting, and quantum state redistribution (up to a certain optimization in the
      latter case). We also present a port-based teleportation scheme which uses a
      fewer number of ports in the presence of information about input.

PMID- 29341639
TI  - Enhanced Second-Order Nonlinearity for THz Generation by Resonant Interaction of
      Exciton-Polariton Rabi Oscillations with Optical Phonons.
AB  - Semiconductor microcavities in the strong-coupling regime exhibit an energy scale
      in the terahertz (THz) frequency range, which is fixed by the Rabi splitting
      between the upper and lower exciton-polariton states. While this range can be
      tuned by several orders of magnitude using different excitonic media, the
      transition between both polaritonic states is dipole forbidden. In this work, we
      show that, in cadmium telluride microcavities, the Rabi-oscillation-driven THz
      radiation is actually active without the need for any change in the microcavity
      design. This feature results from the unique resonance condition which is
      achieved between the Rabi splitting and the phonon-polariton states and leads to
      a giant enhancement of the second-order nonlinearity.

PMID- 29341640
TI  - Role of Intrapulse Coherence in Carrier-Envelope Phase Stabilization.
AB  - The concept of coherence is of fundamental importance for describing the physical
      characteristics of light and for evaluating the suitability for experimental
      application. In the case of pulsed laser sources, the pulse-to-pulse coherence is
      usually considered for a judgment of the compressibility of the pulse train. This
      type of coherence is often lost during propagation through a highly nonlinear
      medium, and pulses prove incompressible despite multioctave spectral coverage.
      Notwithstanding the apparent loss of interpulse coherence, however, supercontinua
      enable applications in precision frequency metrology that rely on coherence
      between different spectral components within a laser pulse. To judge the
      suitability of a light source for the latter application, we define an
      alternative criterion, which we term intrapulse coherence. This definition plays
      a limiting role in the carrier-envelope phase measurement and stabilization of
      ultrashort pulses. It is shown by numerical simulation and further corroborated
      by experimental data that filamentation-based supercontinuum generation may lead
      to a loss of intrapulse coherence despite near-perfect compressibility of the
      pulse train. This loss of coherence may severely limit active and passive carrier
      envelope phase stabilization schemes and applications in optical high-field
      physics.

PMID- 29341641
TI  - Simultaneous Deep Tunneling and Classical Hopping for Hydrogen Diffusion on
      Metals.
AB  - Hydrogen diffusion on metals exhibits rich quantum behavior, which is not yet
      fully understood. Using simulations, we show that many hydrogen diffusion
      barriers can be categorized into those with parabolic tops and those with broad
      tops. With parabolic-top barriers, hydrogen diffusion evolves gradually from
      classical hopping, to shallow tunneling, to deep tunneling as the temperature (T)
      decreases, and noticeable quantum effects persist at moderate T. In contrast,
      with broad-top barriers quantum effects become important only at low T and the
      classical-to-quantum transition is sharp, at which classical hopping and deep
      tunneling both occur. This coexistence indicates that more than one mechanism
      contributes to the quantum reaction rate. The conventional definition of the
      classical-to-quantum crossover T is invalid for the broad tops, and we give a new
      definition. Extending this, we propose a model to predict the transition T for
      broad-top diffusion, providing a general guide for theory and experiment.

PMID- 29341642
TI  - Magnetic Proximity Effects in Transition-Metal Dichalcogenides: Converting
      Excitons.
AB  - The two-dimensional character and reduced screening in monolayer transition-metal
      dichalcogenides (TMDs) lead to the ubiquitous formation of robust excitons with
      binding energies orders of magnitude larger than in bulk semiconductors. Focusing
      on neutral excitons, bound electron-hole pairs that dominate the optical response
      in TMDs, it is shown that they can provide fingerprints for magnetic proximity
      effects in magnetic heterostructures. These proximity effects cannot be described
      by the widely used single-particle description but instead reveal the possibility
      of a conversion between optically inactive and active excitons by rotating the
      magnetization of the magnetic substrate. With recent breakthroughs in fabricating
      Mo- and W-based magnetic TMD heterostructures, this emergent optical response can
      be directly tested experimentally.

PMID- 29341643
TI  - Generalized Magnetic Mirrors.
AB  - We propose generalized magnetic mirrors that can be achieved by excitations of
      sole electric resonances. Conventional approaches to obtain magnetic mirrors rely
      heavily on exciting the fundamental magnetic dipoles, whereas here we reveal
      that, besides magnetic resonances, electric resonances of higher orders can be
      also employed to obtain highly efficient magnetic mirrors. Based on the
      electromagnetic duality, it is also shown that electric mirrors can be achieved
      by exciting magnetic resonances. We provide direct demonstrations of the
      generalized mirrors proposed in a simple system of a one-dimensional periodic
      array of all-dielectric wires, which may shed new light on many advanced fields
      of photonics related to resonant multipolar excitations and interferences.

PMID- 29341644
TI  - Scale-Dependent Stiffness and Internal Tension of a Model Brush Polymer.
AB  - Bottle-brush polymers exhibit closely grafted side chains that interact by steric
      repulsion, thereby causing stiffening of the main polymer chain. We use single
      molecule elasticity measurements of model brush polymers to quantify this effect.
      We find that stiffening is only significant on long length scales, with the main
      chain retaining flexibility on short scales. From the elasticity data, we extract
      an estimate of the internal tension generated by side-chain repulsion; this
      estimate is consistent with the predictions of blob-based scaling theories.

PMID- 29341645
TI  - Contextuality as a Resource for Models of Quantum Computation with Qubits.
AB  - A central question in quantum computation is to identify the resources that are
      responsible for quantum speed-up. Quantum contextuality has been recently shown
      to be a resource for quantum computation with magic states for odd-prime
      dimensional qudits and two-dimensional systems with real wave functions. The
      phenomenon of state-independent contextuality poses a priori an obstruction to
      characterizing the case of regular qubits, the fundamental building block of
      quantum computation. Here, we establish contextuality of magic states as a
      necessary resource for a large class of quantum computation schemes on qubits. We
      illustrate our result with a concrete scheme related to measurement-based quantum
      computation.

PMID- 29341646
TI  - Erratum: Ultimate Precision of Adaptive Noise Estimation [Phys. Rev. Lett. 118,
      100502 (2017)].
AB  - This corrects the article DOI: 10.1103/PhysRevLett.118.100502.

PMID- 29341647
TI  - Attosecond Electron Correlation Dynamics in Double Ionization of Benzene Probed
      with Two-Electron Angular Streaking.
AB  - With a novel three-dimensional electron-electron coincidence imaging technique
      and two-electron angular streaking method, we show that the emission time delay
      between two electrons can be measured from tens of attoseconds to more than 1 fs.
      Surprisingly, in benzene, the double ionization rate decays as the time delay
      between the first and second electron emission increases during the first 500 as.
      This is further supported by the decay of the Coulomb repulsion in the direction
      perpendicular to the laser polarization. This result reveals that laser-induced
      electron correlation plays a major role in strong field double ionization of
      benzene driven by a nearly circularly polarized field.

PMID- 29341648
TI  - Thermal Transport in the Kitaev Model.
AB  - In conventional insulating magnets, heat is carried by magnons and phonons. In
      contrast, when the magnets harbor a quantum spin liquid state, emergent
      quasiparticles from the fractionalization of quantum spins can carry heat. Here,
      we investigate unconventional thermal transport yielded by such exotic carriers,
      in both longitudinal and transverse components, for the Kitaev model, whose
      ground state is exactly shown to be a quantum spin liquid with fractional
      excitations described as itinerant Majorana fermions and localized Z_{2} fluxes.
      We find that the longitudinal thermal conductivity exhibits a single peak at a
      high temperature, while the nonzero frequency component has a peak at a low
      temperature, reflecting the spin fractionalization. On the other hand, we show
      that the transverse thermal conductivity is induced by the magnetic field in a
      wide temperature range up to the energy scale of the bare exchange coupling;
      while increasing temperature, the transverse response divided by temperature
      decreases from the quantized value expected for the topologically nontrivial
      ground state and shows nonmonotonic temperature dependence. These characteristic
      behaviors provide experimentally accessible evidence of fractional excitations in
      the proximity to the Kitaev quantum spin liquid.

PMID- 29341649
TI  - Gaussian Hypothesis Testing and Quantum Illumination.
AB  - Quantum hypothesis testing is one of the most basic tasks in quantum information
      theory and has fundamental links with quantum communication and estimation
      theory. In this paper, we establish a formula that characterizes the decay rate
      of the minimal type-II error probability in a quantum hypothesis test of two
      Gaussian states given a fixed constraint on the type-I error probability. This
      formula is a direct function of the mean vectors and covariance matrices of the
      quantum Gaussian states in question. We give an application to quantum
      illumination, which is the task of determining whether there is a low
      reflectivity object embedded in a target region with a bright thermal-noise bath.
      For the asymmetric-error setting, we find that a quantum illumination transmitter
      can achieve an error probability exponent stronger than a coherent-state
      transmitter of the same mean photon number, and furthermore, that it requires far
      fewer trials to do so. This occurs when the background thermal noise is either
      low or bright, which means that a quantum advantage is even easier to witness
      than in the symmetric-error setting because it occurs for a larger range of
      parameters. Going forward from here, we expect our formula to have applications
      in settings well beyond those considered in this paper, especially to quantum
      communication tasks involving quantum Gaussian channels.

PMID- 29341650
TI  - Characterization of the ^{163}Ho Electron Capture Spectrum: A Step Towards the
      Electron Neutrino Mass Determination.
AB  - The isotope ^{163}Ho is in many ways the best candidate to perform experiments to
      investigate the value of the electron neutrino mass. It undergoes an electron
      capture process to ^{163}Dy with an energy available to the decay, Q_{EC}, of
      about 2.8 keV. According to the present knowledge, this is the lowest Q_{EC}
      value for such transitions. Here we discuss a newly obtained spectrum of
      ^{163}Ho, taken by cryogenic metallic magnetic calorimeters with ^{163}Ho
      implanted in the absorbers and operated in anticoincident mode for background
      reduction. For the first time, the atomic deexcitation of the ^{163}Dy daughter
      atom following the capture of electrons from the 5s shell in ^{163}Ho, the OI
      line, was observed with a calorimetric measurement. The peak energy is determined
      to be 48 eV. In addition, a precise determination of the energy available for the
      decay Q_{EC}=(2.858+/-0.010_{stat}+/-0.05_{syst})  keV was obtained by analyzing
      the intensities of the lines in the spectrum. This value is in good agreement
      with the measurement of the mass difference between ^{163}Ho and ^{163}Dy
      obtained by Penning-trap mass spectrometry, demonstrating the reliability of the
      calorimetric technique.

PMID- 29341651
TI  - Lattice Homotopy Constraints on Phases of Quantum Magnets.
AB  - The Lieb-Schultz-Mattis (LSM) theorem and its extensions forbid trivial phases
      from arising in certain quantum magnets. Constraining infrared behavior with the
      ultraviolet data encoded in the microscopic lattice of spins, these theorems tie
      the absence of spontaneous symmetry breaking to the emergence of exotic phases
      like quantum spin liquids. In this work, we take a new topological perspective on
      these theorems, by arguing they originate from an obstruction to "trivializing"
      the lattice under smooth, symmetric deformations, which we call the "lattice
      homotopy problem." We conjecture that all LSM-like theorems for quantum magnets
      (many previously unknown) can be understood from lattice homotopy, which
      automatically incorporates the full spatial symmetry group of the lattice,
      including all its point-group symmetries. One consequence is that any spin
      symmetric magnet with a half-integer moment on a site with even-order rotational
      symmetry must be a spin liquid. To substantiate the claim, we prove the
      conjecture in two dimensions for some physically relevant settings.

PMID- 29341652
TI  - Cascade of Magnetic-Field-Induced Lifshitz Transitions in the Ferromagnetic Kondo
      Lattice Material YbNi_{4}P_{2}.
AB  - A ferromagnetic quantum critical point is thought not to exist in two- and three
      dimensional metallic systems yet is realized in the Kondo lattice compound
      YbNi_{4}(P,As)_{2}, possibly due to its one-dimensionality. It is crucial to
      investigate the dimensionality of the Fermi surface of YbNi_{4}P_{2}
      experimentally, but common probes such as angle-resolved photoemission
      spectroscopy and quantum oscillation measurements are lacking. Here, we study the
      magnetic-field dependence of transport and thermodynamic properties of
      YbNi_{4}P_{2}. The Kondo effect is continuously suppressed, and additionally we
      identify nine Lifshitz transitions between 0.4 and 18 T. We analyze the transport
      coefficients in detail and identify the type of Lifshitz transitions as neck or
      void type to gain information on the Fermi surface of YbNi_{4}P_{2}. The large
      number of Lifshitz transitions observed within this small energy window is
      unprecedented and results from the particular flat renormalized band structure
      with strong 4f-electron character shaped by the Kondo lattice effect.

PMID- 29341653
TI  - Quantum Nonlinear Optics in Optomechanical Nanoscale Waveguides.
AB  - We show that strong nonlinearities at the few photon level can be achieved in
      optomechanical nanoscale waveguides. We consider the propagation of photons in cm
      scale one-dimensional nanophotonic structures where stimulated Brillouin
      scattering (SBS) is strongly enhanced by radiation pressure coupling. We
      introduce a configuration that allows slowing down photons by several orders of
      magnitude via SBS from sound waves using two pump fields. Slowly propagating
      photons can then experience strong nonlinear interactions through virtual off
      resonant exchange of dispersionless phonons. As a benchmark we identify
      requirements for achieving a large cross-phase modulation among two
      counterpropagating photons applicable for photonic quantum gates. Our results
      indicate that strongly nonlinear quantum optics is possible in continuum
      optomechanical systems realized in nanophotonic structures.

PMID- 29341654
TI  - Revealing Nonclassicality of Inaccessible Objects.
AB  - Some physical objects are hardly accessible to direct experimentation. It is then
      desirable to infer their properties based solely on the interactions they have
      with systems over which we have control. In this spirit, here we introduce
      schemes for assessing the nonclassicality of the inaccessible objects as
      characterized by quantum discord. We consider two probes individually interacting
      with the inaccessible object but not with each other. The schemes are based on
      monitoring entanglement dynamics between the probes. Our method is robust and
      experimentally friendly, as it allows the probes and the object to be open
      systems and makes no assumptions about the initial state, dimensionality of
      involved Hilbert spaces, and details of the probe-object Hamiltonian. We apply
      our scheme to a membrane-in-the-middle optomechanical system, to detect system
      environment correlations in open system dynamics as well as nonclassicality of
      the environment, and we foresee potential benefits for the inference of the
      nonclassical nature of gravity.

PMID- 29341655
TI  - Plasmons in Dimensionally Mismatched Coulomb Coupled Graphene Systems.
AB  - We calculate the plasmon dispersion relation for Coulomb coupled metallic
      armchair graphene nanoribbons and doped monolayer graphene. The crossing of the
      plasmon curves, which occurs for uncoupled 1D and 2D systems, is split by the
      interlayer Coulomb coupling into a lower and an upper plasmon branch. The upper
      branch exhibits an unusual behavior with end points at finite q. Accordingly, the
      structure factor shows either a single or a double peak behavior, depending on
      the plasmon wavelength. The new plasmon structure is relevant to recent
      experiments, its properties can be controlled by varying the system parameters
      and be used in plasmonic applications.

PMID- 29341656
TI  - Quantum Correlations in Nonlocal Boson Sampling.
AB  - Determination of the quantum nature of correlations between two spatially
      separated systems plays a crucial role in quantum information science. Of
      particular interest is the questions of if and how these correlations enable
      quantum information protocols to be more powerful. Here, we report on a
      distributed quantum computation protocol in which the input and output quantum
      states are considered to be classically correlated in quantum informatics.
      Nevertheless, we show that the correlations between the outcomes of the
      measurements on the output state cannot be efficiently simulated using classical
      algorithms. Crucially, at the same time, local measurement outcomes can be
      efficiently simulated on classical computers. We show that the only known
      classicality criterion violated by the input and output states in our protocol is
      the one used in quantum optics, namely, phase-space nonclassicality. As a result,
      we argue that the global phase-space nonclassicality inherent within the output
      state of our protocol represents true quantum correlations.

PMID- 29341657
TI  - Triple Junction at the Triple Point Resolved on the Individual Particle Level.
AB  - At the triple point of a repulsive screened Coulomb system, a fcc crystal, a bcc
      crystal, and a fluid phase coexist. At their intersection, these three phases
      form a liquid groove, the triple junction. Using confocal microscopy, we resolve
      the triple junction on a single-particle level in a model system of charged PMMA
      colloids in a nonpolar solvent. The groove is found to be extremely deep and the
      incommensurate solid-solid interface to be very broad. Thermal fluctuations hence
      appear to dominate the solid-solid interface. This indicates a very low
      interfacial energy. The fcc-bcc interfacial energy is quantitatively determined
      based on Young's equation and, indeed, it is only about 1.3 times higher than the
      fcc-fluid interfacial energy close to the triple point.

PMID- 29341658
TI  - Floquet Symmetry-Protected Topological Phases in Cold-Atom Systems.
AB  - We propose and analyze two distinct routes toward realizing interacting symmetry
      protected topological (SPT) phases via periodic driving. First, we demonstrate
      that a driven transverse-field Ising model can be used to engineer complex
      interactions which enable the emulation of an equilibrium SPT phase. This phase
      remains stable only within a parametric time scale controlled by the driving
      frequency, beyond which its topological features break down. To overcome this
      issue, we consider an alternate route based upon realizing an intrinsically
      Floquet SPT phase that does not have any equilibrium analog. In both cases, we
      show that disorder, leading to many-body localization, prevents runaway heating
      and enables the observation of coherent quantum dynamics at high energy
      densities. Furthermore, we clarify the distinction between the equilibrium and
      Floquet SPT phases by identifying a unique micromotion-based entanglement
      spectrum signature of the latter. Finally, we propose a unifying implementation
      in a one-dimensional chain of Rydberg-dressed atoms and show that protected edge
      modes are observable on realistic experimental time scales.

PMID- 29341659
TI  - New Boundary-Driven Twist States in Systems with Broken Spatial Inversion
      Symmetry.
AB  - A full description of a magnetic sample includes a correct treatment of the
      boundary conditions (BCs). This is in particular important in thin film systems,
      where even bulk properties might be modified by the properties of the boundary of
      the sample. We study generic ferromagnets with broken spatial inversion symmetry
      and derive the general micromagnetic BCs of a system with Dzyaloshinskii-Moriya
      interaction (DMI). We demonstrate that the BCs require the full tensorial
      structure of the third-rank DMI tensor and not just the antisymmetric part, which
      is usually taken into account. Specifically, we study systems with C_{infinityv}
      symmetry and explore the consequences of the DMI. Interestingly, we find that the
      DMI already in the simplest case of a ferromagnetic thin film leads to a purely
      boundary-driven magnetic twist state at the edges of the sample. The twist state
      represents a new type of DMI-induced spin structure, which is completely
      independent of the internal DMI field. We estimate the size of the texture
      induced magnetoresistance effect being in the range of that of domain walls.

PMID- 29341660
TI  - 2D Stress Tensor for 4D Gravity.
AB  - We use the subleading soft-graviton theorem to construct an operator T_{zz} whose
      insertion in the four-dimensional tree-level quantum gravity S matrix obeys the
      Virasoro-Ward identities of the energy momentum tensor of a two-dimensional
      conformal field theory (CFT_{2}). The celestial sphere at Minkowskian null
      infinity plays the role of the Euclidean sphere of the CFT_{2}, with the Lorentz
      group acting as the unbroken SL(2,C) subgroup.

PMID- 29341661
TI  - Entanglement Hamiltonians for Chiral Fermions with Zero Modes.
AB  - In this Letter, we study the effect of topological zero modes on entanglement
      Hamiltonians and the entropy of free chiral fermions in (1+1)D. We show how
      Riemann-Hilbert solutions combined with finite rank perturbation theory allow us
      to obtain exact expressions for entanglement Hamiltonians. In the absence of the
      zero mode, the resulting entanglement Hamiltonians consist of local and bilocal
      terms. In the periodic sector, the presence of a zero mode leads to an additional
      nonlocal contribution to the entanglement Hamiltonian. We derive an exact
      expression for this term and for the resulting change in the entanglement
      entropy.

PMID- 29341662
TI  - Reentrant Phase Diagram of Yb_{2}Ti_{2}O_{7} in a ?111? Magnetic Field.
AB  - We present a magnetic phase diagram of rare-earth pyrochlore Yb_{2}Ti_{2}O_{7} in
      a ?111? magnetic field. Using heat capacity, magnetization, and neutron
      scattering data, we show an unusual field dependence of a first-order phase
      boundary, wherein a small applied field increases the ordering temperature. The
      zero-field ground state has ferromagnetic domains, while the spins polarize along
      ?111? above 0.65 T. A classical Monte Carlo analysis of published Hamiltonians
      does account for the critical field in the low T limit. However, this analysis
      fails to account for the large bulge in the reentrant phase diagram, suggesting
      that either long-range interactions or quantum fluctuations govern low field
      properties.

PMID- 29341663
TI  - Conditional Hybrid Nonclassicality.
AB  - We derive and implement a general method to characterize the nonclassicality in
      compound discrete- and continuous-variable systems. For this purpose, we
      introduce the operational notion of conditional hybrid nonclassicality which
      relates to the ability to produce a nonclassical continuous-variable state by
      projecting onto a general superposition of discrete-variable subsystem. We
      discuss the importance of this form of quantumness in connection with interfaces
      for quantum communication. To verify the conditional hybrid nonclassicality, a
      matrix version of a nonclassicality quasiprobability is derived and its sampling
      approach is formulated. We experimentally generate an entangled, hybrid
      Schrodinger cat state, using a coherent photon-addition process acting on two
      temporal modes, and we directly sample its nonclassicality quasiprobability
      matrix. The introduced conditional quantum effects are certified with high
      statistical significance.

PMID- 29341664
TI  - Optimal Continuous Variable Quantum Teleportation with Limited Resources.
AB  - Given a certain amount of entanglement available as a resource, what is the most
      efficient way to accomplish a quantum task? We address this question in the
      relevant case of continuous variable quantum teleportation protocols implemented
      using two-mode Gaussian states with a limited degree of entanglement and energy.
      We first characterize the class of single-mode phase-insensitive Gaussian
      channels that can be simulated via a Braunstein-Kimble protocol with nonunit gain
      and minimum shared entanglement, showing that infinite energy is not necessary
      apart from the special case of the quantum limited attenuator. We also find that
      apart from the identity, all phase-insensitive Gaussian channels can be simulated
      through a two-mode squeezed state with finite energy, albeit with a larger
      entanglement. We then consider the problem of teleporting single-mode coherent
      states with Gaussian-distributed displacement in phase space. Performing a
      geometrical optimization over phase-insensitive Gaussian channels, we determine
      the maximum average teleportation fidelity achievable with any finite
      entanglement and for any realistically finite variance of the input distribution.

PMID- 29341665
TI  - Can Hail and Rain Nucleate Cloud Droplets?
AB  - We present results from moist convection in a mixture of pressurized sulfur
      hexafluoride (liquid and vapor), and helium (gas) to model the wet and dry
      components of the Earth's atmosphere. To allow for homogeneous nucleation, we
      operate the experiment close to critical conditions. We report on the nucleation
      of microdroplets in the wake of large cold liquid drops falling through the
      supersaturated atmosphere and show that the homogeneous nucleation is caused by
      isobaric cooling of the saturated sulfur hexafluoride vapor. Our results carry
      over to atmospheric clouds: falling hail and cold rain drops may enhance the
      heterogeneous nucleation of microdroplets in their wake under supersaturated
      atmospheric conditions. We also observed that under appropriate circumstances
      settling microdroplets form a rather stable horizontal cloud layer, which
      separates regions of super- and subcritical saturation.

PMID- 29341666
TI  - Mechanism behind Erosive Bursts In Porous Media.
AB  - Erosion and deposition during flow through porous media can lead to large erosive
      bursts that manifest as jumps in permeability and pressure loss. Here we reveal
      that the cause of these bursts is the reopening of clogged pores when the
      pressure difference between two opposite sites of the pore surpasses a certain
      threshold. We perform numerical simulations of flow through porous media and
      compare our predictions to experimental results, recovering with excellent
      agreement shape and power-law distribution of pressure loss jumps, and the
      behavior of the permeability jumps as a function of particle concentration.
      Furthermore, we find that erosive bursts only occur for pressure gradient
      thresholds within the range of two critical values, independent of how the flow
      is driven. Our findings provide a better understanding of sudden sand production
      in oil wells and breakthrough in filtration.

PMID- 29341667
TI  - Dark Kinetic Heating of Neutron Stars and an Infrared Window on WIMPs, SIMPs, and
      Pure Higgsinos.
AB  - We identify a largely model-independent signature of dark matter (DM)
      interactions with nucleons and electrons. DM in the local galactic halo,
      gravitationally accelerated to over half the speed of light, scatters against and
      deposits kinetic energy into neutron stars, heating them to infrared blackbody
      temperatures. The resulting radiation could potentially be detected by the James
      Webb Space Telescope, the Thirty Meter Telescope, or the European Extremely Large
      Telescope. This mechanism also produces optical emission from neutron stars in
      the galactic bulge, and x-ray emission near the galactic center because dark
      matter is denser in these regions. For GeV-PeV mass dark matter, dark kinetic
      heating would initially unmask any spin-independent or spin-dependent dark matter
      nucleon cross sections exceeding 2*10^{-45}  cm^{2}, with improved sensitivity
      after more telescope exposure. For lighter-than-GeV dark matter, cross-section
      sensitivity scales inversely with dark matter mass because of Pauli blocking; for
      heavier-than-PeV dark matter, it scales linearly with mass as a result of needing
      multiple scatters for capture. Future observations of dark sector-warmed neutron
      stars could determine whether dark matter annihilates in or only kinetically
      heats neutron stars. Because inelastic interstate transitions of up to a few GeV
      would occur in relativistic scattering against nucleons, elusive inelastic dark
      matter like pure Higgsinos can also be discovered.

PMID- 29341668
TI  - Modular Invariance of Conformal Field Theory on S^{1}*S^{3} and Circle
      Fibrations.
AB  - I conjecture a high-temperature-low-temperature duality for conformal field
      theories defined on circle fibrations like S^{3} and its lens space family. The
      duality is an exchange between the thermal circle and the fiber circle in the
      limit where both are small. The conjecture is motivated by the fact that
      pi_{1}(S^{3}/Z_{p->infinity})=Z=pi_{1}(S^{1}*S^{2}) and the Gromov-Hausdorff
      distance between S^{3}/Z_{p->infinity} and S^{1}/Z_{p->infinity}*S^{2} vanishes.
      Several checks of the conjecture are provided: free fields, N=1 theories in four
      dimensions (which shows that the Di Pietro-Komargodski supersymmetric Cardy
      formula and its generalizations are given exactly by a supersymmetric Casimir
      energy), N=4 super Yang-Mills at strong coupling, and the six-dimensional N=(2,0)
      theory. For all examples considered, the duality is powerful enough to control
      the high-temperature asymptotics on the unlensed S^{3}, relating it to the
      Casimir energy on a highly lensed S^{3}. Such large-order quotients are more
      generally useful for studying quantum field theory on curved spacetimes.

PMID- 29341669
TI  - Precision Measurement of Time-Reversal Symmetry Violation with Laser-Cooled
      Polyatomic Molecules.
AB  - Precision searches for time-reversal symmetry violating interactions in polar
      molecules are extremely sensitive probes of high energy physics beyond the
      standard model. To extend the reach of these probes into the PeV regime, long
      coherence times and large count rates are necessary. Recent advances in laser
      cooling of polar molecules offer one important tool-optical trapping. However,
      the types of molecules that have been laser cooled so far do not have the highly
      desirable combination of features for new physics searches, such as the ability
      to fully polarize and the existence of internal comagnetometer states. We show
      that by utilizing the internal degrees of freedom present only in molecules with
      at least three atoms, these features can be attained simultaneously with
      molecules that have simple structure and are amenable to laser cooling and
      trapping.

PMID- 29341670
TI  - Surface Polarization Effects on Ion-Containing Emulsions.
AB  - Surface polarization in ion-containing heterogeneous dielectric media such as
      cell media and emulsions is determined by and determines the positions of the
      ions. We compute the surface polarization self-consistently as the ions move and
      analyze their effects on the interactions between electro-neutral, ion-containing
      droplets using coarse-grained molecular dynamics simulations based on the true
      energy functional. For water droplets immersed in oil, the interdroplet
      interaction is attractive, and the surface polarization makes the major
      contribution. By contrast, for oil droplets in water, the ion-surface induced
      charge interaction is repulsive and counteracts the attraction between the ions,
      leading to a small attractive interaction between the droplets. This research
      improves our understanding of self-assembly in mixed phases such as metal
      extraction for recovering rare earth elements and nuclear waste as well as water
      purification.

PMID- 29341671
TI  - Ab initio Exchange-Correlation Free Energy of the Uniform Electron Gas at Warm
      Dense Matter Conditions.
AB  - In a recent Letter [T. Dornheim et al., Phys. Rev. Lett. 117, 156403
      (2016)PRLTAO0031-900710.1103/PhysRevLett.117.156403], we presented the first
      quantum Monte Carlo (QMC) results for the warm dense electron gas in the
      thermodynamic limit. However, a complete parametrization of the exchange
      correlation free energy with respect to density, temperature, and spin
      polarization remained out of reach due to the absence of (i) accurate QMC results
      below theta=k_{B}T/E_{F}=0.5 and (ii) QMC results for spin polarizations
      different from the paramagnetic case. Here we overcome both remaining
      limitations. By closing the gap to the ground state and by performing extensive
      QMC simulations for different spin polarizations, we are able to obtain the first
      completely ab initio exchange-correlation free energy functional; the accuracy
      achieved is an unprecedented ~0.3%. This also allows us to quantify the accuracy
      and systematic errors of various previous approximate functionals.

PMID- 29341672
TI  - Helicase Stepping Investigated with One-Nucleotide Resolution Fluorescence
      Resonance Energy Transfer.
AB  - Single-molecule Forster resonance energy transfer is widely applied to study
      helicases by detecting distance changes between a pair of dyes anchored to
      overhangs of a forked DNA. However, it has been lacking single-base pair (1-bp)
      resolution required for revealing stepping kinetics of helicases. We designed a
      nanotensioner in which a short DNA is bent to exert force on the overhangs, just
      as in optical or magnetic tweezers. The strategy improved the resolution of
      Forster resonance energy transfer to 0.5 bp, high enough to uncover differences
      in DNA unwinding by yeast Pif1 and E. coli RecQ whose unwinding behaviors cannot
      be differentiated by currently practiced methods. We found that Pif1 exhibits 1
      bp-stepping kinetics, while RecQ breaks 1 bp at a time but sequesters the nascent
      nucleotides and releases them randomly. The high-resolution data allowed us to
      propose a three-parameter model to quantitatively interpret the apparently
      different unwinding behaviors of the two helicases which belong to two
      superfamilies.

PMID- 29341673
TI  - Chiral Spin Mode on the Surface of a Topological Insulator.
AB  - Using polarization-resolved resonant Raman spectroscopy, we explore collective
      spin excitations of the chiral surface states in a three dimensional topological
      insulator, Bi_{2}Se_{3}. We observe a sharp peak at 150 meV in the pseudovector
      A_{2} symmetry channel of the Raman spectra. By comparing the data with
      calculations, we identify this peak as the transverse collective spin mode of
      surface Dirac fermions. This mode, unlike a Dirac plasmon or a surface plasmon in
      the charge sector of excitations, is analogous to a spin wave in a partially
      polarized Fermi liquid, with spin-orbit coupling playing the role of an effective
      magnetic field.

PMID- 29341674
TI  - Stochastic and Resolvable Gravitational Waves from Ultralight Bosons.
AB  - Ultralight scalar fields around spinning black holes can trigger superradiant
      instabilities, forming a long-lived bosonic condensate outside the horizon. We
      use numerical solutions of the perturbed field equations and astrophysical models
      of massive and stellar-mass black hole populations to compute, for the first
      time, the stochastic gravitational-wave background from these sources. In
      optimistic scenarios the background is observable by Advanced LIGO and LISA for
      field masses m_{s} in the range ~[2*10^{-13},10^{-12}] and ~5*[10^{-19},10^{-16}]
      eV, respectively, and it can affect the detectability of resolvable sources. Our
      estimates suggest that an analysis of the stochastic background limits from LIGO
      O1 might already be used to marginally exclude axions with mass ~10^{-12.5}  eV.
      Semicoherent searches with Advanced LIGO (LISA) should detect ~15(5) to 200(40)
      resolvable sources for scalar field masses 3*10^{-13} (10^{-17})  eV. LISA
      measurements of massive BH spins could either rule out bosons in the range ~[10^{
      18},2*10^{-13}]  eV, or measure m_{s} with 10% accuracy in the range ~[10^{
      17},10^{-13}]  eV.

PMID- 29341675
TI  - Many-Molecule Reaction Triggered by a Single Photon in Polaritonic Chemistry.
AB  - The second law of photochemistry states that, in most cases, no more than one
      molecule is activated for an excited-state reaction for each photon absorbed by a
      collection of molecules. In this Letter, we demonstrate that it is possible to
      trigger a many-molecule reaction using only one photon by strongly coupling the
      molecular ensemble to a confined light mode. The collective nature of the
      resulting hybrid states of the system (the so-called polaritons) leads to the
      formation of a polaritonic "supermolecule" involving the degrees of freedom of
      all molecules, opening a reaction path on which all involved molecules undergo a
      chemical transformation. We theoretically investigate the system conditions for
      this effect to take place and be enhanced.

PMID- 29341676
TI  - Excess Hydrogen Bond at the Ice-Vapor Interface around 200 K.
AB  - Phase-resolved sum-frequency generation measurements combined with molecular
      dynamics simulations are employed to study the effect of temperature on the
      molecular arrangement of water on the basal face of ice. The topmost monolayer,
      interrogated through its nonhydrogen-bonded, free O-H stretch peak, exhibits a
      maximum in surface H-bond density around 200 K. This maximum results from two
      competing effects: above 200 K, thermal fluctuations cause the breaking of H
      bonds; below 200 K, the formation of bulklike crystalline interfacial structures
      leads to H-bond breaking. Knowledge of the surface structure of ice is critical
      for understanding reactions occurring on ice surfaces and ice nucleation.

PMID- 29341677
TI  - Current-Nonlinear Hall Effect and Spin-Orbit Torque Magnetization Switching in a
      Magnetic Topological Insulator.
AB  - The current-nonlinear Hall effect or second harmonic Hall voltage is widely used
      as one of the methods for estimating charge-spin conversion efficiency, which is
      attributed to the magnetization oscillation by spin-orbit torque (SOT). Here, we
      argue the second harmonic Hall voltage under a large in-plane magnetic field with
      an in-plane magnetization configuration in magnetic-nonmagnetic topological
      insulator (TI) heterostructures, Cr_{x}(Bi_{1-y}Sb_{y})_{2-x}Te_{3}/(Bi_{1
      y}Sb_{y})_{2}Te_{3}, where it is clearly shown that the large second harmonic
      voltage is governed not by SOT but mainly by asymmetric magnon scattering without
      macroscopic magnetization oscillation. Thus, this method does not allow an
      accurate estimation of charge-spin conversion efficiency in TI. Instead, the SOT
      contribution is exemplified by current pulse induced nonvolatile magnetization
      switching, which is realized with a current density of 2.5*10^{10}  A m^{-2},
      showing its potential as a spintronic material.

PMID- 29341678
TI  - Erratum: Distinct Turbulence Saturation Regimes in Stellarators [Phys. Rev. Lett.
      118, 105002 (2017)].
AB  - This corrects the article DOI: 10.1103/PhysRevLett.118.105002.

PMID- 29341679
TI  - Detection of the Spin-Chemical Potential in Topological Insulators Using Spin
      Polarized Four-Probe STM.
AB  - We demonstrate a new method for the detection of the spin-chemical potential in
      topological insulators using spin-polarized four-probe scanning tunneling
      microscopy on in situ cleaved Bi_{2}Te_{2}Se surfaces. Two-dimensional (2D)
      surface and 3D bulk conductions are separated quantitatively via variable probe
      spacing measurements, enabling the isolation of the nonvanishing spin-dependent
      electrochemical potential from the Ohmic contribution. This component is
      identified as the spin-chemical potential arising from the 2D charge current
      through the spin momentum locked topological surface states (TSS). This method
      provides a direct measurement of spin current generation efficiency and opens a
      new avenue to access the intrinsic spin transport associated with pristine TSS.

PMID- 29341681
TI  - Determining Quiescent Colloidal Suspension Viscosities Using the Green-Kubo
      Relation and Image-Based Stress Measurements.
AB  - By combining confocal microscopy and stress assessment from local structural
      anisotropy, we directly measure stresses in 3D quiescent colloidal liquids. Our
      noninvasive and nonperturbative method allows us to measure forces ?50  fN with a
      small and tunable probing volume, enabling us to resolve the stress fluctuations
      arising from particle thermal motions. We use the Green-Kubo relation to relate
      these measured stress fluctuations to the bulk Brownian viscosity at different
      volume fractions, comparing against simulations and conventional rheometry
      measurements. We find that the Green-Kubo analysis gives excellent agreement with
      these prior results, suggesting that similar methods could be applied to
      investigations of local flow properties in many poorly understood far-from
      equilibrium systems, including suspensions that are glassy, strongly sheared, or
      highly confined.

PMID- 29341680
TI  - Ultimate Stable Underwater Superhydrophobic State.
AB  - Underwater metastability hinders the durable application of superhydrophobic
      surfaces. In this work, through thermodynamic analysis, we theoretically
      demonstrate the existence of an ultimate stable state on underwater
      superhydrophobic surfaces. Such a state is achieved by the synergy of mechanical
      balance and chemical diffusion equilibrium across the entrapped liquid-air
      interfaces. By using confocal microscopy, we in situ examine the ultimate stable
      states on structured hydrophobic surfaces patterned with cylindrical micropores
      in different pressure and flow conditions. The equilibrium morphology of the
      meniscus is tuned by the dissolved gas saturation degree within a critical range
      at a given liquid pressure. Moreover, with fresh lotus leaves, we prove that the
      ultimate stable state can also be realized on randomly rough superhydrophobic
      surfaces. The finding here paves the way for applying superhydrophobic surfaces
      in environments with different liquid pressure and flow conditions.

PMID- 29341682
TI  - Gate-Controlled Spin-Valley Locking of Resident Carriers in WSe_{2} Monolayers.
AB  - Using time-resolved Kerr rotation, we measure the spin-valley dynamics of
      resident electrons and holes in single charge-tunable monolayers of the
      archetypal transition-metal dichalcogenide (TMD) semiconductor WSe_{2}. In the n
      type regime, we observe long (~130  ns) polarization relaxation of electrons that
      is sensitive to in-plane magnetic fields B_{y}, indicating spin relaxation. In
      marked contrast, extraordinarily long (~2  MUs) polarization relaxation of holes
      is revealed in the p-type regime, which is unaffected by B_{y}, directly
      confirming long-standing expectations of strong spin-valley locking of holes in
      the valence band of monolayer TMDs. Supported by continuous-wave Kerr
      spectroscopy and Hanle measurements, these studies provide a unified picture of
      carrier polarization dynamics in monolayer TMDs, which can guide design
      principles for future valleytronic devices.

PMID- 29341683
TI  - Theory of Thermal Relaxation of Electrons in Semiconductors.
AB  - We compute the transient dynamics of phonons in contact with high energy "hot"
      charge carriers in 12 polar and nonpolar semiconductors, using a first-principles
      Boltzmann transport framework. For most materials, we find that the decay in
      electronic temperature departs significantly from a single-exponential model at
      times ranging from 1 to 15 ps after electronic excitation, a phenomenon
      concomitant with the appearance of nonthermal vibrational modes. We demonstrate
      that these effects result from slow thermalization within the phonon subsystem,
      caused by the large heterogeneity in the time scales of electron-phonon and
      phonon-phonon interactions in these materials. We propose a generalized two
      temperature model accounting for phonon thermalization as a limiting step of
      electron-phonon thermalization, which captures the full thermal relaxation of hot
      electrons and holes in semiconductors. A direct consequence of our findings is
      that, for semiconductors, information about the spectral distribution of electron
      phonon and phonon-phonon coupling can be extracted from the multiexponential
      behavior of the electronic temperature.

PMID- 29341684
TI  - First Simultaneous Extraction of Spin-Dependent Parton Distributions and
      Fragmentation Functions from a Global QCD Analysis.
AB  - We perform the first global QCD analysis of polarized inclusive and semi
      inclusive deep-inelastic scattering and single-inclusive e^{+}e^{-} annihilation
      data, simultaneously fitting the parton distribution and fragmentation functions
      using the iterative Monte Carlo method. Without imposing SU(3) symmetry
      relations, we find the strange polarization to be very small, consistent with
      zero for both inclusive and semi-inclusive data, which provides a resolution to
      the strange quark polarization puzzle. The combined analysis also allows the
      direct extraction from data of the isovector and octet axial charges, and is
      consistent with a small SU(2) flavor asymmetry in the polarized sea.

PMID- 29341685
TI  - Intermittent Granular Dynamics at a Seismogenic Plate Boundary.
AB  - Earthquakes at seismogenic plate boundaries are a response to the differential
      motions of tectonic blocks embedded within a geometrically complex network of
      branching and coalescing faults. Elastic strain is accumulated at a slow strain
      rate on the order of 10^{-15}  s^{-1}, and released intermittently at intervals
      >100  yr, in the form of rapid (seconds to minutes) coseismic ruptures. The
      development of macroscopic models of quasistatic planar tectonic dynamics at
      these plate boundaries has remained challenging due to uncertainty with regard to
      the spatial and kinematic complexity of fault system behaviors. The
      characteristic length scale of kinematically distinct tectonic structures is
      particularly poorly constrained. Here, we analyze fluctuations in Global
      Positioning System observations of interseismic motion from the southern
      California plate boundary, identifying heavy-tailed scaling behavior. Namely, we
      show that, consistent with findings for slowly sheared granular media, the
      distribution of velocity fluctuations deviates from a Gaussian, exhibiting broad
      tails, and the correlation function decays as a stretched exponential. This
      suggests that the plate boundary can be understood as a densely packed granular
      medium, predicting a characteristic tectonic length scale of 91+/-20  km, here
      representing the characteristic size of tectonic blocks in the southern
      California fault network, and relating the characteristic duration and recurrence
      interval of earthquakes, with the observed sheared strain rate, and the
      nanosecond value for the crack tip evolution time scale. Within a granular
      description, fault and blocks systems may rapidly rearrange the distribution of
      forces within them, driving a mixture of transient and intermittent fault slip
      behaviors over tectonic time scales.

PMID- 29341686
TI  - Nonequilibrium Chromosome Looping via Molecular Slip Links.
AB  - We propose a model for the formation of chromatin loops based on the diffusive
      sliding of molecular slip links. These mimic the behavior of molecules like
      cohesin, which, along with the CTCF protein, stabilize loops which contribute to
      organizing the genome. By combining 3D Brownian dynamics simulations and 1D
      exactly solvable nonequilibrium models, we show that diffusive sliding is
      sufficient to account for the strong bias in favor of convergent CTCF-mediated
      chromosome loops observed experimentally. We also find that the diffusive motion
      of multiple slip links along chromatin is rectified by an intriguing ratchet
      effect that arises if slip links bind to the chromatin at a preferred "loading
      site." This emergent collective behavior favors the extrusion of loops which are
      much larger than the ones formed by single slip links.

PMID- 29341687
TI  - Maximally Symmetric Composite Higgs Models.
AB  - Maximal symmetry is a novel tool for composite pseudo Goldstone boson Higgs
      models: it is a remnant of an enhanced global symmetry of the composite fermion
      sector involving a twisting with the Higgs field. Maximal symmetry has far
      reaching consequences: it ensures that the Higgs potential is finite and fully
      calculable, and also minimizes the tuning. We present a detailed analysis of the
      maximally symmetric SO(5)/SO(4) model and comment on its observational
      consequences.

PMID- 29341688
TI  - What Randomized Benchmarking Actually Measures.
AB  - Randomized benchmarking (RB) is widely used to measure an error rate of a set of
      quantum gates, by performing random circuits that would do nothing if the gates
      were perfect. In the limit of no finite-sampling error, the exponential decay
      rate of the observable survival probabilities, versus circuit length, yields a
      single error metric r. For Clifford gates with arbitrary small errors described
      by process matrices, r was believed to reliably correspond to the mean, over all
      Clifford gates, of the average gate infidelity between the imperfect gates and
      their ideal counterparts. We show that this quantity is not a well-defined
      property of a physical gate set. It depends on the representations used for the
      imperfect and ideal gates, and the variant typically computed in the literature
      can differ from r by orders of magnitude. We present new theories of the RB decay
      that are accurate for all small errors describable by process matrices, and show
      that the RB decay curve is a simple exponential for all such errors. These
      theories allow explicit computation of the error rate that RB measures (r), but
      as far as we can tell it does not correspond to the infidelity of a physically
      allowed (completely positive) representation of the imperfect gates.

PMID- 29341689
TI  - Prediction of Triple Point Fermions in Simple Half-Heusler Topological
      Insulators.
AB  - We predict the existence of triple point fermions in the band structure of
      several half-Heusler topological insulators by ab initio calculations and the
      Kane model. We find that many half-Heusler compounds exhibit multiple triple
      points along four independent C_{3} axes, through which the doubly degenerate
      conduction bands and the nondegenerate valence band cross each other linearly
      nearby the Fermi energy. When projected from the bulk to the (111) surface, most
      of these triple points are located far away from the surface Gamma[over -] point,
      as distinct from previously reported triple point fermion candidates. These
      isolated triple points give rise to Fermi arcs on the surface, that can be
      readily detected by photoemission spectroscopy or scanning tunneling
      spectroscopy.

PMID- 29341690
TI  - Anomalous Nonlocal Resistance and Spin-Charge Conversion Mechanisms in Two
      Dimensional Metals.
AB  - We uncover two anomalous features in the nonlocal transport behavior of two
      dimensional metallic materials with spin-orbit coupling. First, the nonlocal
      resistance can have negative values and oscillate with distance, even in the
      absence of a magnetic field. Second, the oscillations of the nonlocal resistance
      under an applied in-plane magnetic field (the Hanle effect) can be asymmetric
      under field reversal. Both features are produced by direct magnetoelectric
      coupling, which is possible in materials with broken inversion symmetry but was
      not included in previous spin-diffusion theories of nonlocal transport. These
      effects can be used to identify the relative contributions of different spin
      charge conversion mechanisms. They should be observable in adatom-functionalized
      graphene, and they may provide the reason for discrepancies in recent nonlocal
      transport experiments on graphene.

PMID- 29341691
TI  - Dissipative Effects on Inertial-Range Statistics at High Reynolds Numbers.
AB  - Using the unique capabilities of the Variable Density Turbulence Tunnel at the
      Max Planck Institute for Dynamics and Self-Organization, Gottingen, we report
      experimental measurements in classical grid turbulence that uncover oscillations
      of the velocity structure functions in the inertial range. This was made possible
      by measuring extremely long time series of up to 10^{10} samples of the turbulent
      fluctuating velocity, which corresponds to O(10^{7}) integral length scales. The
      measurements were conducted in a well-controlled environment at a wide range of
      high Reynolds numbers from R_{lambda}=110 up to R_{lambda}=1600, using both
      traditional hot-wire probes as well as the nanoscale thermal anemometry probe
      developed at Princeton University. An implication of the observed oscillations is
      that dissipation influences the inertial-range statistics of turbulent flows at
      scales significantly larger than predicted by current models and theories.

PMID- 29341692
TI  - Nontrivial Chern Numbers in Three-Terminal Josephson Junctions.
AB  - Recently, it has been predicted that the Andreev bound state spectrum of four
      terminal Josephson junctions may possess zero-energy Weyl singularities. Using
      one superconducting phase as a control parameter, these singularities are
      associated with topological transitions between time-reversal symmetry broken
      phases with different Chern numbers. Here we show that such topological
      transitions may also be tuned with a magnetic flux through the junction area in a
      three-terminal geometry.

PMID- 29341693
TI  - Erratum: Evidence for a Phase Transition in Silicate Melt at Extreme Pressure and
      Temperature Conditions [Phys. Rev. Lett. 108, 065701 (2012)].
AB  - This corrects the article DOI: 10.1103/PhysRevLett.108.065701.

PMID- 29341694
TI  - Publisher's Note: Solar Irradiance Variability is Caused by the Magnetic Activity
      on the Solar Surface [Phys. Rev. Lett. 119, 091102 (2017)].
AB  - This corrects the article DOI: 10.1103/PhysRevLett.119.091102.

PMID- 29341695
TI  - Scaling of Majorana Zero-Bias Conductance Peaks.
AB  - We report an experimental study of the scaling of zero-bias conductance peaks
      compatible with Majorana zero modes as a function of magnetic field, tunnel
      coupling, and temperature in one-dimensional structures fabricated from an
      epitaxial semiconductor-superconductor heterostructure. Results are consistent
      with theory, including a peak conductance that is proportional to tunnel
      coupling, saturates at 2e^{2}/h, decreases as expected with field-dependent gap,
      and collapses onto a simple scaling function in the dimensionless ratio of
      temperature and tunnel coupling.

PMID- 29341696
TI  - Coherent Beam-Beam Instability in Collisions with a Large Crossing Angle.
AB  - In recent years the "crab-waist collision" scheme [P. Raimondi, Proceedings of
      2nd SuperB Workshop, Frascati, 2006.; M. Zobov et al., Phys. Rev. Lett. 104,
      174801 (2010)PRLTAO0031-900710.1103/PhysRevLett.104.174801] has become popular
      for circular e^{+} e^{-} colliders. The designs of several future colliders are
      based on this scheme. So far the beam-beam effects for collisions under a large
      crossing angle with or without crab waist were mostly studied using weak-strong
      simulations. We present here strong-strong simulations showing a novel strong
      coherent head-tail instability, which can limit the performance of proposed
      future colliders. We explain the underlying instability mechanism starting from
      the "cross-wake force" induced by the beam-beam interaction. Using this beam-beam
      wake, the beam-beam head tail modes are studied by an eigenmode analysis. The
      instability may affect all collider designs based on the crab-waist scheme. We
      suggest an experimental verification at SuperKEKB during its commissioning phase
      II.

PMID- 29341697
TI  - Large-Scale Structure and Hyperuniformity of Amorphous Ices.
AB  - We investigate the large-scale structure of amorphous ices and transitions
      between their different forms by quantifying their large-scale density
      fluctuations. Specifically, we simulate the isothermal compression of low-density
      amorphous ice (LDA) and hexagonal ice to produce high-density amorphous ice
      (HDA). Both HDA and LDA are nearly hyperuniform; i.e., they are characterized by
      an anomalous suppression of large-scale density fluctuations. By contrast, in
      correspondence with the nonequilibrium phase transitions to HDA, the presence of
      structural heterogeneities strongly suppresses the hyperuniformity and the system
      becomes hyposurficial (devoid of "surface-area fluctuations"). Our investigation
      challenges the largely accepted "frozen-liquid" picture, which views glasses as
      structurally arrested liquids. Beyond implications for water, our findings enrich
      our understanding of pressure-induced structural transformations in glasses.

PMID- 29341698
TI  - General Linearized Theory of Quantum Fluctuations around Arbitrary Limit Cycles.
AB  - The theory of Gaussian quantum fluctuations around classical steady states in
      nonlinear quantum-optical systems (also known as standard linearization) is a
      cornerstone for the analysis of such systems. Its simplicity, together with its
      accuracy far from critical points or situations where the nonlinearity reaches
      the strong coupling regime, has turned it into a widespread technique, being the
      first method of choice in most works on the subject. However, such a technique
      finds strong practical and conceptual complications when one tries to apply it to
      situations in which the classical long-time solution is time dependent, a most
      prominent example being spontaneous limit-cycle formation. Here, we introduce a
      linearization scheme adapted to such situations, using the driven Van der Pol
      oscillator as a test bed for the method, which allows us to compare it with full
      numerical simulations. On a conceptual level, the scheme relies on the connection
      between the emergence of limit cycles and the spontaneous breaking of the
      symmetry under temporal translations. On the practical side, the method keeps the
      simplicity and linear scaling with the size of the problem (number of modes)
      characteristic of standard linearization, making it applicable to large (many
      body) systems.

PMID- 29341699
TI  - Emission of Nonclassical Radiation by Inelastic Cooper Pair Tunneling.
AB  - We show that a properly dc-biased Josephson junction in series with two microwave
      resonators of different frequencies emits photon pairs in the resonators. By
      measuring auto- and intercorrelations of the power leaking out of the resonators,
      we demonstrate two-mode amplitude squeezing below the classical limit. This
      nonclassical microwave light emission is found to be in quantitative agreement
      with our theoretical predictions, up to an emission rate of 2 billion photon
      pairs per second.

PMID- 29341700
TI  - Optimal Measurements for Simultaneous Quantum Estimation of Multiple Phases.
AB  - A quantum theory of multiphase estimation is crucial for quantum-enhanced sensing
      and imaging and may link quantum metrology to more complex quantum computation
      and communication protocols. In this Letter, we tackle one of the key
      difficulties of multiphase estimation: obtaining a measurement which saturates
      the fundamental sensitivity bounds. We derive necessary and sufficient conditions
      for projective measurements acting on pure states to saturate the ultimate
      theoretical bound on precision given by the quantum Fisher information matrix. We
      apply our theory to the specific example of interferometric phase estimation
      using photon number measurements, a convenient choice in the laboratory. Our
      results thus introduce concepts and methods relevant to the future theoretical
      and experimental development of multiparameter estimation.

PMID- 29341701
TI  - 3D Quantum Hall Effect of Fermi Arcs in Topological Semimetals.
AB  - The quantum Hall effect is usually observed in 2D systems. We show that the Fermi
      arcs can give rise to a distinctive 3D quantum Hall effect in topological
      semimetals. Because of the topological constraint, the Fermi arc at a single
      surface has an open Fermi surface, which cannot host the quantum Hall effect. Via
      a "wormhole" tunneling assisted by the Weyl nodes, the Fermi arcs at opposite
      surfaces can form a complete Fermi loop and support the quantum Hall effect. The
      edge states of the Fermi arcs show a unique 3D distribution, giving an example of
      (d-2)-dimensional boundary states. This is distinctly different from the surface
      state quantum Hall effect from a single surface of topological insulator. As the
      Fermi energy sweeps through the Weyl nodes, the sheet Hall conductivity evolves
      from the 1/B dependence to quantized plateaus at the Weyl nodes. This behavior
      can be realized by tuning gate voltages in a slab of topological semimetal, such
      as the TaAs family, Cd_{3}As_{2}, or Na_{3}Bi. This work will be instructive not
      only for searching transport signatures of the Fermi arcs but also for exploring
      novel electron gases in other topological phases of matter.

PMID- 29341702
TI  - Kinetic Energy of a Trapped Fermi Gas at Finite Temperature.
AB  - We study the statistics of the kinetic (or, equivalently, potential) energy for N
      noninteracting fermions in a 1d harmonic trap of frequency omega at finite
      temperature T. Remarkably, we find an exact solution for the full distribution of
      the kinetic energy, at any temperature T and for any N, using a nontrivial
      mapping to an integrable Calogero-Moser-Sutherland model. As a function of
      temperature T and for large N, we identify (i) a quantum regime, for T~homega,
      where quantum fluctuations dominate and (ii) a thermal regime, for T~Nhomega,
      governed by thermal fluctuations. We show how the mean and the variance as well
      as the large deviation function associated with the distribution of the kinetic
      energy cross over from the quantum to the thermal regime as T increases.

PMID- 29341703
TI  - Negative Landau Damping in Bilayer Graphene.
AB  - We theoretically demonstrate that a system formed by two coupled graphene sheets
      enables a negative damping regime wherein graphene plasmons are pumped by a
      direct current. This effect is triggered by electrons drifting through one of the
      graphene sheets and leads to wave instabilities and a spontaneous light emission
      (spasing) in the midinfrared range. It is shown that there is a deep link between
      the drift-induced instabilities and wave instabilities in moving media, as both
      result from the hybridization of oscillators with oppositely signed frequencies.
      With a thickness of a few nanometers and wide spectral tunability, the proposed
      structure may find interesting applications in nanophotonic circuitry as an on
      chip light source.

PMID- 29341704
TI  - Anomaly Indicators for Time-Reversal Symmetric Topological Orders.
AB  - Some time-reversal symmetric topological orders are anomalous in that they cannot
      be realized in strictly two-dimensional systems; instead, they can only be
      realized on the surface of three-dimensional symmetry-protected topological
      phases. We propose two quantities, which we call anomaly indicators, that can
      detect if a time-reversal symmetric topological order is anomalous in this sense.
      Both anomaly indicators are expressed in terms of the quantum dimensions,
      topological spins, and time-reversal properties of the anyons in the given
      topological order. The first indicator, eta_{2}, applies to bosonic systems while
      the second indicator, eta_{f}, applies to fermionic systems in the DIII class. We
      conjecture that eta_{2}, together with a previously known indicator eta_{1}, can
      detect the two known Z_{2} anomalies in the bosonic case, while eta_{f} can
      detect the Z_{16} anomaly in the fermionic case.

PMID- 29341705
TI  - Electromagnetic Charge Radius of the Pion at High Precision.
AB  - We present a determination of the pion charge radius from high precision data on
      the pion vector form factor from both timelike and spacelike regions, using a
      novel formalism based on analyticity and unitarity. At low energies, instead of
      the poorly known modulus of the form factor, we use its phase, known with high
      accuracy from Roy equations for pipi elastic scattering via the Fermi-Watson
      theorem. We use also the values of the modulus at several higher timelike
      energies, where the data from e^{+}e^{-} annihilation and tau decay are mutually
      consistent, as well as the most recent measurements at spacelike momenta. The
      experimental uncertainties are implemented by Monte Carlo simulations. The
      results, which do not rely on a specific parametrization, are optimal for the
      given input information and do not depend on the unknown phase of the form factor
      above the first inelastic threshold. Our prediction for the charge radius of the
      pion is r_{pi}=(0.657+/-0.003)  fm, which amounts to an increase in precision by
      a factor of about 2.7 compared to the Particle Data Group average.

PMID- 29341706
TI  - Optical Force Enhancement Using an Imaginary Vector Potential for Photons.
AB  - The enhancement of optical forces has enabled a variety of technological
      applications that rely on the optical control of small objects and devices.
      Unfortunately, optical forces are still too small for the convenient actuation of
      integrated switches and waveguide couplers. Here we show how the optical gradient
      force can be enhanced by an order of magnitude by making use of gauge materials
      inside two evanescently coupled waveguides. To this end, the gauge materials
      inside the cores should emulate imaginary vector potentials for photons pointing
      perpendicularly to the waveguide plane. Depending on the relative orientation of
      the vector potentials in neighboring waveguides, i.e., pointing away from or
      towards each other, the conventional attractive force due to an even mode profile
      may be enhanced, suppressed, or may even become repulsive. This and other new
      features indicate that the implementation of complex-valued vector potentials
      with non-Hermitian waveguide cores may further enhance our control over mode
      profiles and the associated optical forces.

PMID- 29341707
TI  - Anomalous Acoustic Plasmon Mode from Topologically Protected States.
AB  - Plasmons, the collective excitations of electrons in the bulk or at the surface,
      play an important role in the properties of materials, and have generated the
      field of "plasmonics." We report the observation of a highly unusual acoustic
      plasmon mode on the surface of a three-dimensional topological insulator (TI)
      Bi_{2}Se_{3}, using momentum resolved inelastic electron scattering. In sharp
      contrast to ordinary plasmon modes, this mode exhibits almost linear dispersion
      into the second Brillouin zone and remains prominent with remarkably weak damping
      not seen in any other systems. This behavior must be associated with the inherent
      robustness of the electrons in the TI surface state, so that not only the surface
      Dirac states but also their collective excitations are topologically protected.
      On the other hand, this mode has much smaller energy dispersion than expected
      from a continuous media excitation picture, which can be attributed to the strong
      coupling with surface phonons.

PMID- 29341708
TI  - High-Precision Probe of the Fully Sequential Decay Width of the Hoyle State in
      ^{12}C.
AB  - The decay path of the Hoyle state in ^{12}C (E_{x}=7.654  MeV) has been studied
      with the ^{14}N(d,alpha_{2})^{12}C(7.654) reaction induced at 10.5 MeV. High
      resolution invariant mass spectroscopy techniques have allowed us to
      unambiguously disentangle direct and sequential decays of the state passing
      through the ground state of ^{8}Be. Thanks to the almost total absence of
      background and the attained resolution, a fully sequential decay contribution to
      the width of the state has been observed. The direct decay width is negligible,
      with an upper limit of 0.043% (95% C.L.). The precision of this result is about a
      factor 5 higher than previous studies. This has significant implications on
      nuclear structure, as it provides constraints to 3alpha cluster model
      calculations, where higher precision limits are needed.

PMID- 29341709
TI  - Probing Primordial Black Hole Dark Matter with Gravitational Waves.
AB  - Primordial black holes (PBHs) have long been suggested as a candidate for making
      up some or all of the dark matter in the Universe. Most of the theoretically
      possible mass range for PBH dark matter has been ruled out with various null
      observations of expected signatures of their interaction with standard
      astrophysical objects. However, current constraints are significantly less robust
      in the 20  M_{?}?M_{PBH}?100  M_{?} mass window, which has received much
      attention recently, following the detection of merging black holes with estimated
      masses of ~30  M_{?} by LIGO and the suggestion that these could be black holes
      formed in the early Universe. We consider the potential of advanced LIGO (aLIGO)
      operating at design sensitivity to probe this mass range by looking for peaks in
      the mass spectrum of detected events. To quantify the background, which is due to
      black holes that are formed from dying stars, we model the shape of the stellar
      black-hole mass function and calibrate its amplitude to match the O1 results.
      Adopting very conservative assumptions about the PBH and stellar-black-hole
      merger rates, we show that ~5  yr of aLIGO data can be used to detect a
      contribution of >20  M_{?} PBHs to dark matter down to f_{PBH}<0.5 at >99.9%
      confidence level. Combined with other probes that already suggest tension with
      f_{PBH}=1, the obtainable independent limits from aLIGO will thus enable a firm
      test of the scenario that PBHs make up all of dark matter.

PMID- 29341710
TI  - Vibrational Action Spectroscopy of Solids: New Surface-Sensitive Technique.
AB  - Vibrational action spectroscopy employing infrared radiation from a free-electron
      laser has been successfully used for many years to study the vibrational and
      structural properties of gas phase aggregates. Despite the high sensitivity of
      this method no relevant studies have yet been conducted for solid sample
      surfaces. We have set up an experiment for the application of this method to such
      targets, using infrared light from the free-electron laser of the Fritz Haber
      Institute. In this Letter, we present first results of this technique with
      adsorbed argon and neon atoms as messengers. We were able to detect surface
      located vibrations of a thin V_{2}O_{3}(0001) film on Au(111) as well as
      adsorbate vibrations, demonstrating that this method is highly surface sensitive.
      We consider that the dominant channel for desorption of the messenger atoms is
      direct inharmonic vibrational coupling, which is essentially insensitive to
      subsurface or bulk vibrations. Another channel is thermal desorption due to
      sample heating by absorption of infrared light. The high surface sensitivity of
      the nonthermal channel and its insensitivity to subsurface modes makes this
      technique an ideal tool for the study of surface-located vibrations.

PMID- 29341711
TI  - Macroscopic Polarization from Antiferrodistortive Cycloids in Ferroelastic
      SrTiO_{3}.
AB  - Based on a first-principles based multiscale approach, we study the polarity P of
      ferroelastic twin walls in SrTiO_{3}. In addition to flexoelectricity, which was
      pointed out before, we identify two new mechanisms that crucially contribute to
      P: a direct "rotopolar" coupling to the gradients of the antiferrodistortive
      oxygen tilts, and a trilinear coupling that is mediated by the antiferroelectric
      displacement of the Ti atoms. Remarkably, the rotopolar coupling presents a
      strong analogy to the mechanism that generates a spontaneous polarization in
      cycloidal magnets. We show how this similarity allows for a breakdown of
      macroscopic inversion symmetry (and therefore a macroscopic polarization) in a
      periodic sequence of parallel twins. These results open new avenues towards
      engineering pyroelectricity or piezoelectricity in nominally nonpolar ferroic
      materials.

PMID- 29341712
TI  - Spatial Multiplexing of Atom-Photon Entanglement Sources using Feedforward
      Control and Switching Networks.
AB  - The light-matter quantum interface that can create quantum correlations or
      entanglement between a photon and one atomic collective excitation is a
      fundamental building block for a quantum repeater. The intrinsic limit is that
      the probability of preparing such nonclassical atom-photon correlations has to be
      kept low in order to suppress multiexcitation. To enhance this probability
      without introducing multiexcitation errors, a promising scheme is to apply
      multimode memories to the interface. Significant progress has been made in
      temporal, spectral, and spatial multiplexing memories, but the enhanced
      probability for generating the entangled atom-photon pair has not been
      experimentally realized. Here, by using six spin-wave-photon entanglement
      sources, a switching network, and feedforward control, we build a multiplexed
      light-matter interface and then demonstrate a ~sixfold (~fourfold) probability
      increase in generating entangled atom-photon (photon-photon) pairs. The measured
      compositive Bell parameter for the multiplexed interface is 2.49+/-0.03 combined
      with a memory lifetime of up to ~51  MUs.

PMID- 29341713
TI  - Field-Induced Instability of a Gapless Spin Liquid with a Spinon Fermi Surface.
AB  - The ground state of the quantum kagome antiferromagnet Zn-brochantite,
      ZnCu_{3}(OH)_{6}SO_{4}, which is one of only a few known spin-liquid (SL)
      realizations in two or three dimensions, has been described as a gapless SL with
      a spinon Fermi surface. Employing nuclear magnetic resonance in a broad magnetic
      field range down to millikelvin temperatures, we show that in applied magnetic
      fields this enigmatic state is intrinsically unstable against a SL with a full or
      a partial gap. A similar instability of the gapless Fermi-surface SL was
      previously encountered in an organic triangular-lattice antiferromagnet,
      suggesting a common destabilization mechanism that most likely arises from spinon
      pairing. A salient property of this instability is that an infinitesimal field
      suffices to induce it, as predicted theoretically for some other types of gapless
      SLs.

PMID- 29341714
TI  - Kinetically Controlled Two-Step Amorphization and Amorphous-Amorphous Transition
      in Ice.
AB  - We report the results of in situ structural characterization of the amorphization
      of crystalline ice Ih under compression and the relaxation of high-density
      amorphous (HDA) ice under decompression at temperatures between 96 and 160 K by
      synchrotron x-ray diffraction. The results show that ice Ih transforms to an
      intermediate crystalline phase at 100 K prior to complete amorphization, which is
      supported by molecular dynamics calculations. The phase transition pathways show
      clear temperature dependence: direct amorphization without an intermediate phase
      is observed at 133 K, while at 145 K a direct Ih-to-IX transformation is
      observed; decompression of HDA shows a transition to low-density amorphous ice at
      96 K and ~1  Pa, to ice Ic at 135 K and to ice IX at 145 K. These observations
      show that the amorphization of compressed ice Ih and the recrystallization of
      decompressed HDA are strongly dependent on temperature and controlled by kinetic
      barriers. Pressure-induced amorphous ice is an intermediate state in the phase
      transition from the connected H-bond water network in low pressure ices to the
      independent and interpenetrating H-bond network of high-pressure ices.

PMID- 29341715
TI  - Potential Energy Surface Reconstruction and Lifetime Determination of Molecular
      Double-Core-Hole States in the Hard X-Ray Regime.
AB  - A combination of resonant inelastic x-ray scattering and resonant Auger
      spectroscopy provides complementary information on the dynamic response of
      resonantly excited molecules. This is exemplified for CH_{3}I, for which we
      reconstruct the potential energy surface of the dissociative I 3d^{-2} double
      core-hole state and determine its lifetime. The proposed method holds a strong
      potential for monitoring the hard x-ray induced electron and nuclear dynamic
      response of core-excited molecules containing heavy elements, where ab initio
      calculations of potential energy surfaces and lifetimes remain challenging.

PMID- 29341716
TI  - Single-Electron and Single-Photon Sensitivity with a Silicon Skipper CCD.
AB  - We have developed ultralow-noise electronics in combination with repetitive,
      nondestructive readout of a thick, fully depleted charge-coupled device (CCD) to
      achieve an unprecedented noise level of 0.068  e^{-} rms/pixel. This is the first
      time that discrete subelectron readout noise has been achieved reproducible over
      millions of pixels on a stable, large-area detector. This enables the
      contemporaneous, discrete, and quantized measurement of charge in pixels,
      irrespective of whether they contain zero electrons or thousands of electrons.
      Thus, the resulting CCD detector is an ultra-sensitive calorimeter. It is also
      capable of counting single photons in the optical and near-infrared regime.
      Implementing this innovative non-destructive readout system has a negligible
      impact on CCD design and fabrication, and there are nearly immediate scientific
      applications. As a particle detector, this CCD will have unprecedented
      sensitivity to low-mass dark matter particles and coherent neutrino-nucleus
      scattering, while future astronomical applications may include direct imaging and
      spectroscopy of exoplanets.

PMID- 29341717
TI  - Magnetic Circular Dichroism in X-Ray Emission from Ferromagnets.
AB  - The existence of novel magnetic circular dichroism in core-level x-ray emission
      is reported. By means of circular polarization analysis, the dichroic effect of
      the Fe Kalpha_{1} emission spectrum is measured on an Fe single crystal. The
      observed dichroic effect (12%) is remarkably large, if one takes into account the
      small dichroic effect (about 0.5%) in the conventional K-edge absorption
      spectroscopy of 3d transition metal elements. The mechanism is ascribed to
      exchange splitting of the 2p level possessing large spin-orbit coupling. This new
      magnetooptical effect enables us to explore a variety of new research subjects in
      the magnetism of 3d transition metals and their compounds by fully utilizing its
      large dichroic effect, the true bulk sensitivity of hard x rays, and the element
      selectivity of core-level spectroscopy.

PMID- 29341719
TI  - Detecting Topological Invariants in Nonunitary Discrete-Time Quantum Walks.
AB  - We report the experimental detection of bulk topological invariants in nonunitary
      discrete-time quantum walks with single photons. The nonunitarity of the quantum
      dynamics is enforced by periodically performing partial measurements on the
      polarization of the walker photon, which effectively introduces loss to the
      dynamics. The topological invariant of the nonunitary quantum walk is manifested
      in the quantized average displacement of the walker, which is probed by
      monitoring the photon loss. We confirm the topological properties of the system
      by observing localized edge states at the boundary of regions with different
      topological invariants. We further demonstrate the robustness of both the
      topological properties and the measurement scheme of the topological invariants
      against disorder.

PMID- 29341720
TI  - Magnetic Skyrmions and Skyrmion Clusters in the Helical Phase of Cu_{2}OSeO_{3}.
AB  - Skyrmions are nanometric spin whirls that can be stabilized in magnets lacking
      inversion symmetry. The properties of isolated Skyrmions embedded in a
      ferromagnetic background have been intensively studied. We show that single
      Skyrmions and clusters of Skyrmions can also form in the helical phase and
      investigate theoretically their energetics and dynamics. The helical background
      provides natural one-dimensional channels along which a Skyrmion can move
      rapidly. In contrast to Skyrmions in ferromagnets, the Skyrmion-Skyrmion
      interaction has a strong attractive component and thus Skyrmions tend to form
      clusters with characteristic shapes. These clusters are directly observed in
      transmission electron microscopy measurements in thin films of Cu_{2}OSeO_{3}.
      Topological quantization, high mobility, and the confinement of Skyrmions in
      channels provided by the helical background may be useful for future spintronics
      devices.

PMID- 29341721
TI  - Nonexponential Quantum Decay under Environmental Decoherence.
AB  - A system prepared in an unstable quantum state generally decays following an
      exponential law, as environmental decoherence is expected to prevent the decay
      products from recombining to reconstruct the initial state. Here we show the
      existence of deviations from exponential decay in open quantum systems under very
      general conditions. Our results are illustrated with the exact dynamics under
      quantum Brownian motion and suggest an explanation of recent experimental
      observations.

PMID- 29341722
TI  - A Laser Excitation Scheme for ^{229m}Th.
AB  - Direct laser excitation of the lowest known nuclear excited state in ^{229}Th has
      been a long-standing objective. It is generally assumed that reaching this goal
      would require a considerably reduced uncertainty of the isomer's excitation
      energy compared to the presently adopted value of (7.8+/-0.5)  eV. Here we
      present a direct laser excitation scheme for ^{229m}Th, which circumvents this
      requirement. The proposed excitation scheme makes use of already existing laser
      technology and therefore paves the way for nuclear laser spectroscopy. In this
      concept, the recently experimentally observed internal-conversion decay channel
      of the isomeric state is used for probing the isomeric population. A signal-to
      background ratio of better than 10^{4} and a total measurement time of less than
      three days for laser scanning appear to be achievable.

PMID- 29341723
TI  - Improving a Solid-State Qubit through an Engineered Mesoscopic Environment.
AB  - A controlled quantum system can alter its environment by feedback, leading to
      reduced-entropy states of the environment and to improved system coherence. Here,
      using a quantum-dot electron spin as a control and probe, we prepare the quantum
      dot nuclei under the feedback of coherent population trapping and observe their
      evolution from a thermal to a reduced-entropy state, with the immediate
      consequence of extended qubit coherence. Via Ramsey interferometry on the
      electron spin, we directly access the nuclear distribution following its
      preparation and measure the emergence and decay of correlations within the
      nuclear ensemble. Under optimal feedback, the inhomogeneous dephasing time of the
      electron, T_{2}^{*}, is extended by an order of magnitude to 39 ns. Our results
      can be readily exploited in quantum information protocols utilizing spin-photon
      entanglement and represent a step towards creating quantum many-body states in a
      mesoscopic nuclear-spin ensemble.

PMID- 29341724
TI  - Landau Damping of Beam Instabilities by Electron Lenses.
AB  - Modern and future particle accelerators employ increasingly higher intensity and
      brighter beams of charged particles and become operationally limited by coherent
      beam instabilities. Usual methods to control the instabilities, such as octupole
      magnets, beam feedback dampers, and use of chromatic effects, become less
      effective and insufficient. We show that, in contrast, Lorentz forces of a low
      energy, magnetically stabilized electron beam, or "electron lens," easily
      introduce transverse nonlinear focusing sufficient for Landau damping of
      transverse beam instabilities in accelerators. It is also important to note that,
      unlike other nonlinear elements, the electron lens provides the frequency spread
      mainly at the beam core, thus allowing much higher frequency spread without
      lifetime degradation. For the parameters of the Future Circular Collider, a
      single conventional electron lens a few meters long would provide stabilization
      superior to tens of thousands of superconducting octupole magnets.

PMID- 29341725
TI  - New Measurement of the Direct 3alpha Decay from the ^{12}C Hoyle State.
AB  - Excited states in certain atomic nuclei possess an unusual structure, where the
      dominant degrees of freedom are those of alpha clusters rather than individual
      nucleons. It has been proposed that the diffuse 3alpha system of the ^{12}C Hoyle
      state may behave like a Bose-Einstein condensate, where the alpha clusters
      maintain their bosonic identities. By measuring the decay of the Hoyle state into
      three alpha particles, we obtained an upper limit for the rare direct 3alpha
      decay branch of 0.047%. This value is now at a level comparable with theoretical
      predictions and could be a sensitive probe of the structure of this state.

PMID- 29341726
TI  - Exposing the QCD Splitting Function with CMS Open Data.
AB  - The splitting function is a universal property of quantum chromodynamics (QCD)
      which describes how energy is shared between partons. Despite its ubiquitous
      appearance in many QCD calculations, the splitting function cannot be measured
      directly, since it always appears multiplied by a collinear singularity factor.
      Recently, however, a new jet substructure observable was introduced which
      asymptotes to the splitting function for sufficiently high jet energies. This
      provides a way to expose the splitting function through jet substructure
      measurements at the Large Hadron Collider. In this Letter, we use public data
      released by the CMS experiment to study the two-prong substructure of jets and
      test the 1->2 splitting function of QCD. To our knowledge, this is the first ever
      physics analysis based on the CMS Open Data.

PMID- 29341727
TI  - Charge Density Waves in Graphite: Towards the Magnetic Ultraquantum Limit.
AB  - Graphite is a model system for the study of three-dimensional electrons and holes
      in the magnetic quantum limit, in which the charges are confined to the lowest
      Landau levels. We report magneto-transport measurements in pulsed magnetic fields
      up to 60 T, which resolve the collapse of two charge density wave states in two,
      electron and hole, Landau levels at 52.3 and 54.2 T, respectively. We report
      evidence for a commensurate charge density wave at 47.1 T in the electron Landau
      level, and discuss the likely nature of the density wave instabilities over the
      full field range. The theoretical modeling of our results predicts that the
      ultraquantum limit is entered above 73.5 T. This state is an insulator, and we
      discuss its correspondence to the "metallic" state reported earlier. We propose
      that this (interaction-induced) insulating phase supports surface states that
      carry no charge or spin within the planes, but does, however, support charge
      transport out of plane.

PMID- 29341728
TI  - Multislip Friction with a Single Ion.
AB  - A trapped ion transported along a periodic potential is studied as a paradigmatic
      nanocontact frictional interface. The combination of the periodic corrugation
      potential and a harmonic trapping potential creates a one-dimensional energy
      landscape with multiple local minima, corresponding to multistable stick-slip
      friction. We measure the probabilities of slipping to the various minima for
      various corrugations and transport velocities. The observed probabilities show
      that the multislip regime can be reached dynamically at smaller corrugations than
      would be possible statically, and can be described by an equilibrium Boltzmann
      model. While a clear microscopic signature of multislip behavior is observed for
      the ion motion, the frictional force and dissipation are only weakly affected by
      the transition to multistable potentials.

PMID- 29341729
TI  - Printing Non-Euclidean Solids.
AB  - Geometrically frustrated solids with a non-Euclidean reference metric are
      ubiquitous in biology and are becoming increasingly relevant in technological
      applications. Often they acquire a targeted configuration of incompatibility
      through the surface accretion of mass as in tree growth or dam construction. We
      use the mechanics of incompatible surface growth to show that geometrical
      frustration developing during deposition can be fine-tuned to ensure a particular
      behavior of the system in physiological (or working) conditions. As an
      illustration, we obtain an explicit 3D printing protocol for arteries, which
      guarantees stress uniformity under inhomogeneous loading, and for explosive
      plants, allowing a complete release of residual elastic energy with a single cut.
      Interestingly, in both cases reaching the physiological target requires the
      incompatibility to have a topological (global) component.

PMID- 29341718
TI  - Search for Invisible Decays of a Dark Photon Produced in e^{+}e^{-} Collisions at
      BaBar.
AB  - We search for single-photon events in 53  fb^{-1} of e^{+}e^{-} collision data
      collected with the BABAR detector at the PEP-II B-Factory. We look for events
      with a single high-energy photon and a large missing momentum and energy,
      consistent with production of a spin-1 particle A^{'} through the process
      e^{+}e^{-}->gammaA^{'}; A^{'}->invisible. Such particles, referred to as "dark
      photons," are motivated by theories applying a U(1) gauge symmetry to dark
      matter. We find no evidence for such processes and set 90% confidence level upper
      limits on the coupling strength of A^{'} to e^{+}e^{-} in the mass range
      m_{A^{'}}<=8  GeV. In particular, our limits exclude the values of the A^{'}
      coupling suggested by the dark-photon interpretation of the muon (g-2)_{MU}
      anomaly, as well as a broad range of parameters for the dark-sector models.

PMID- 29341730
TI  - Polymer Chain Conformation and Dynamical Confinement in a Model One-Component
      Nanocomposite.
AB  - We report a neutron-scattering investigation on the structure and dynamics of a
      single-component nanocomposite based on SiO_{2} particles that were grafted with
      polyisoprene chains at the entanglement limit. By skillful labeling, we access
      both the monomer density in the corona as well as the conformation of the grafted
      chains. While the corona profile follows a r^{-1} power law, the conformation of
      a grafted chain is identical to that of a chain in a reference melt, implying a
      high mutual penetration of the coronas from different particles. The brush
      crowding leads to topological confinement of the chain dynamics: (i) At local
      scales, the segmental dynamics is unchanged compared to the reference melt, while
      (ii) at the scale of the chain, the dynamics appears to be slowed down; (iii) by
      performing a mode analysis in terms of end-fixed Rouse chains, the slower
      dynamics is tracked to topological confinement within the cone spanned by the
      adjacent grafts; (iv) by adding 50% matrix chains, the topological confinement
      sensed by the grafted chain is lifted partially and the apparent chain motion is
      accelerated. We observe a crossover from pure Rouse motion at short times to
      topological confined motion beyond the time when the segmental mean squared
      displacement has reached the distance to the next graft.

PMID- 29341731
TI  - Ultrafocused Electromagnetic Field Pulses with a Hollow Cylindrical Waveguide.
AB  - We theoretically show that a dipole externally driven by a pulse with a lower
      bounded temporal width, and placed inside a cylindrical hollow waveguide, can
      generate a train of arbitrarily short and focused electromagnetic pulses. The
      waveguide encloses vacuum with perfect electric conducting walls. A dipole driven
      by a single short pulse, which is properly engineered to exploit the linear
      spectral filtering of the cylindrical hollow waveguide, excites longitudinal
      waveguide modes that are coherently refocused at some particular instances of
      time, thereby producing arbitrarily short and focused electromagnetic pulses. We
      numerically show that such ultrafocused pulses persist outside the cylindrical
      waveguide at distances comparable to its radius.

PMID- 29341732
TI  - 3D Sisyphus Cooling of Trapped Ions.
AB  - Using a laser polarization gradient, we realize 3D Sisyphus cooling of
      ^{171}Yb^{+} ions confined in and near the Lamb-Dicke regime in a linear Paul
      trap. The cooling rate and final mean motional energy of a single ion are
      characterized as a function of laser intensity and compared to semiclassical and
      quantum simulations. Sisyphus cooling is also applied to a linear string of four
      ions to obtain a mean energy of 1-3 quanta for all vibrational modes, an
      approximately order of magnitude reduction below Doppler cooled energies. This is
      used to enable subsequent, efficient sideband laser cooling.

PMID- 29341733
TI  - Breaking the Temporal Resolution Limit by Superoscillating Optical Beats.
AB  - Band-limited functions can oscillate locally at an arbitrarily fast rate through
      an interference phenomenon known as superoscillations. Using an optical pulse
      with a superoscillatory envelope we experimentally break the temporal Fourier
      transform focusing limit with a temporal feature that is approximately three
      times shorter than the duration of a transform-limited Gaussian pulse having a
      comparable bandwidth while maintaining 30% visibility. We experimentally
      demonstrate the ability of such signals to achieve temporal superresolution and
      show numerically in which cases such pulses can outperform transform-limited
      pulses.

PMID- 29341734
TI  - Vapor-Induced Motion of Liquid Droplets on an Inert Substrate.
AB  - Evaporating droplets are known to show complex motion that has conventionally
      been explained by the Marangoni effect (flow induced by the gradient of surface
      tension). Here, we show that the droplet motion can be induced even in the
      absence of the Marangoni effect due to the gradient of the evaporation rate. We
      derive an equation for the velocity of a droplet subject to the nonuniform
      evaporation rate and nonuniform surface tension placed on an inert substrate,
      where the wettability is uniform and unchanged. The equation explains the
      previously observed attraction-repulsion-chasing behaviors of evaporating
      droplets.

PMID- 29341735
TI  - Complementarity and Polarization Modulation in Photon Interference.
AB  - We derive two general complementarity relations for the distinguishability and
      visibility of genuine vector-light quantum fields in double-pinhole photon
      interference involving polarization modulation. The established framework reveals
      an intrinsic aspect of wave-particle duality of the photon, not previously
      reported, thus providing deeper insights into foundational quantum interference
      physics.

PMID- 29341736
TI  - Emergence of Multiscaling in a Random-Force Stirred Fluid.
AB  - We consider the transition to strong turbulence in an infinite fluid stirred by a
      Gaussian random force. The transition is defined as a first appearance of
      anomalous scaling of normalized moments of velocity derivatives (dissipation
      rates) emerging from the low-Reynolds-number Gaussian background. It is shown
      that, due to multiscaling, strongly intermittent rare events can be
      quantitatively described in terms of an infinite number of different "Reynolds
      numbers" reflecting a multitude of anomalous scaling exponents. The theoretically
      predicted transition disappears at R_{lambda}<=3. The developed theory is in
      quantitative agreement with the outcome of large-scale numerical simulations.

PMID- 29341737
TI  - Superradiant Instability and Backreaction of Massive Vector Fields around Kerr
      Black Holes.
AB  - We study the growth and saturation of the superradiant instability of a complex,
      massive vector (Proca) field as it extracts energy and angular momentum from a
      spinning black hole, using numerical solutions of the full Einstein-Proca
      equations. We concentrate on a rapidly spinning black hole (a=0.99) and the
      dominant m=1 azimuthal mode of the Proca field, with real and imaginary
      components of the field chosen to yield an axisymmetric stress-energy tensor and,
      hence, spacetime. We find that in excess of 9% of the black hole's mass can be
      transferred into the field. In all cases studied, the superradiant instability
      smoothly saturates when the black hole's horizon frequency decreases to match the
      frequency of the Proca cloud that spontaneously forms around the black hole.

PMID- 29341738
TI  - Hierarchy Construction and Non-Abelian Families of Generic Topological Orders.
AB  - We generalize the hierarchy construction to generic 2+1D topological orders
      (which can be non-Abelian) by condensing Abelian anyons in one topological order
      to construct a new one. We show that such construction is reversible and leads to
      a new equivalence relation between topological orders. We refer to the
      corresponding equivalence class (the orbit of the hierarchy construction) as "the
      non-Abelian family." Each non-Abelian family has one or a few root topological
      orders with the smallest number of anyon types. All the Abelian topological
      orders belong to the trivial non-Abelian family whose root is the trivial
      topological order. We show that Abelian anyons in root topological orders must be
      bosons or fermions with trivial mutual statistics between them. The
      classification of topological orders is then greatly simplified, by focusing on
      the roots of each family: those roots are given by non-Abelian modular extensions
      of representation categories of Abelian groups.

PMID- 29341739
TI  - Direct Determination of Dynamic Properties of Coulomb and Yukawa Classical One
      Component Plasmas.
AB  - Dynamic characteristics of strongly coupled classical one-component Coulomb and
      Yukawa plasmas are obtained within the nonperturbative model-free moment approach
      without any data input from simulations so that the dynamic structure factor
      (DSF) satisfies the first three nonvanishing sum rules automatically. The DSF,
      dispersion, decay, sound speed, and other characteristics of the collective modes
      are determined using exclusively the static structure factor calculated from
      various theoretical approaches including the hypernetted chain approximation. A
      good quantitative agreement with molecular dynamics simulation data is achieved.

PMID- 29341740
TI  - Digital Quantum Simulation of Minimal AdS/CFT.
AB  - We propose the digital quantum simulation of a minimal AdS/CFT model in
      controllable quantum platforms. We consider the Sachdev-Ye-Kitaev model
      describing interacting Majorana fermions with randomly distributed all-to-all
      couplings, encoding nonlocal fermionic operators onto qubits to efficiently
      implement their dynamics via digital techniques. Moreover, we also give a method
      for probing nonequilibrium dynamics and the scrambling of information. Finally,
      our approach serves as a protocol for reproducing a simplified low-dimensional
      model of quantum gravity in advanced quantum platforms as trapped ions and
      superconducting circuits.

PMID- 29341741
TI  - Fractional Spin and Josephson Effect in Time-Reversal-Invariant Topological
      Superconductors.
AB  - Time-reversal-invariant topological superconducting (TRITOPS) wires are known to
      host a fractional spin h/4 at their ends. We investigate how this fractional spin
      affects the Josephson current in a TRITOPS-quantum dot-TRITOPS Josephson
      junction, describing the wire in a model that can be tuned between a topological
      and a nontopological phase. We compute the equilibrium Josephson current of the
      full model by continuous-time Monte Carlo simulations and interpret the results
      within an effective low-energy theory. We show that in the topological phase, the
      0-to-pi transition is quenched via formation of a spin singlet from the quantum
      dot spin and the fractional spins associated with the two adjacent topological
      superconductors.

PMID- 29341742
TI  - Measurement of the Electron-Antineutrino Angular Correlation in Neutron beta
      Decay.
AB  - We report the first result for the electron-antineutrino angular correlation (a
      coefficient) in free neutron beta decay from the aCORN experiment. aCORN uses a
      novel method in which the a coefficient is proportional to an asymmetry in proton
      time of flight for events where the beta electron and recoil proton are detected
      in delayed coincidence. Data are presented from a 15 month run at the NIST Center
      for Neutron Research. We obtained a=-0.1090+/-0.0030(stat)+/-0.0028(sys), the
      most precise measurement of the neutron a coefficient reported to date.

PMID- 29341743
TI  - Size-Dependent Localization in Polydisperse Colloidal Glasses.
AB  - We have investigated concentrated suspensions of polydisperse hard spheres and
      have determined the dynamics and sizes of individual particles using confocal
      microscopy. With increasing concentration, the dynamics of the small and large
      particles start to differ. The large particles exhibit slower dynamics and
      stronger localization. Moreover, as the particle size increases, the local volume
      fraction phi_{loc} also increases. In the glass state, the localization length
      significantly decreases beyond phi_{loc}~0.67. This suggests a link between local
      crowding and dynamical heterogeneities. However dynamical arrest of
      subpopulations seems not directly linked to a large value of phi_{loc},
      indicating the importance of collective effects.

PMID- 29341744
TI  - Dynamical Transition of Collective Motions in Dry Proteins.
AB  - Water is widely assumed to be essential for protein dynamics and function. In
      particular, the well-documented "dynamical" transition at ~200  K, at which the
      protein changes from a rigid, nonfunctional form to a flexible, functional state,
      as detected in hydrogenated protein by incoherent neutron scattering, requires
      hydration. Here, we report on coherent neutron scattering experiments on
      perdeuterated proteins and reveal that a transition occurs in dry proteins at the
      same temperature resulting primarily from the collective heavy-atom motions. The
      dynamical transition discovered is intrinsic to the energy landscape of dry
      proteins.

PMID- 29341745
TI  - Born-Oppenheimer Dynamics, Electronic Friction, and the Inclusion of Electron
      Electron Interactions.
AB  - We present a universal expression for the electronic friction as felt by a set of
      classical nuclear degrees of freedom (DOFs) coupled to a manifold of quantum
      electronic DOFs; no assumptions are made regarding the nature of the electronic
      Hamiltonian and electron-electron repulsions are allowed. Our derivation is based
      on a quantum-classical Liouville equation for the coupled electronic-nuclear
      motion, followed by an adiabatic approximation whereby electronic transitions are
      assumed to equilibrate faster than nuclear movement. The resulting form of
      friction is completely general, but does reduce to previously published
      expressions for the quadratic Hamiltonian (i.e., Hamiltonians without electronic
      correlation). At equilibrium, the second fluctuation-dissipation theorem is
      satisfied and the frictional matrix is symmetric. To demonstrate the importance
      of electron-electron correlation, we study electronic friction within the
      Anderson-Holstein model, where a proper treatment of electron-electron
      interactions shows signatures of a Kondo resonance and a mean-field treatment is
      completely inadequate.

PMID- 29341746
TI  - Is the Dispersion Relation Applicable for Exotic Nuclear Systems? The Abnormal
      Threshold Anomaly in the ^{6}He+^{209}Bi System.
AB  - The threshold anomaly of the phenomenological potential has been known for a long
      time in nuclear reactions at energies around the Coulomb barrier, where the
      connection between the real and imaginary potentials is well described by the
      dispersion relation. However, this connection is not clear yet for some weakly
      bound nuclear systems, especially for reactions induced by exotic radioactive
      nuclei. In this study, precise optical potentials of the halo nuclear system
      ^{6}He+^{209}Bi were extracted via ^{208}Pb(^{7}Li,^{6}He) transfer reactions
      with energies measured downward to the extremely sub-barrier region. The real
      potential presents a bell-like shape around the barrier as a normal threshold
      anomaly in tightly bound nuclear systems. However, the imaginary potential shows
      an abnormal behavior: it increases first with energy decreasing below the barrier
      and then falls quickly down to 0. It is the first time the threshold of the
      imaginary potential has been determined in an exotic nuclear system. Moreover,
      experimental results show the dispersion relation is not applicable for this
      system, which may be a common phenomenon for exotic nuclear systems. We discuss
      possible explanations for such a peculiar behavior, but further study is still
      desired for the underlying physics.

PMID- 29341747
TI  - (3+1)D Quasiparticle Anisotropic Hydrodynamics for Ultrarelativistic Heavy-Ion
      Collisions.
AB  - We present the first comparisons of experimental data with phenomenological
      results from (3+1)D quasiparticle anisotropic hydrodynamics (aHydroQP). We
      compare particle spectra, average transverse momentum, and elliptic flow. The
      dynamical equations used for the hydrodynamic stage utilize aHydroQP, which
      naturally includes both shear and bulk viscous effects. The (3+1)D aHydroQP
      evolution obtained is self-consistently converted to hadrons using anisotropic
      Cooper-Frye freeze-out. Hadron production and decays are modeled using a
      customized version of therminator 2. In this first study, we utilized smooth
      Glauber-type initial conditions and a single effective freeze-out temperature
      T_{FO}=130  MeV with all hadronic species in full chemical equilibrium. With this
      rather simple setup, we find a very good description of many heavy-ion
      observables.

PMID- 29341748
TI  - Sliced Basis Density Matrix Renormalization Group for Electronic Structure.
AB  - We introduce a hybrid approach to applying the density matrix renormalization
      group to continuous systems, combining a grid approximation along one direction
      with a finite Gaussian basis set for the remaining two directions. This approach
      is especially useful for chainlike molecules, where the grid is used in the long
      direction. For hydrogen chain systems, the computational time scales
      approximately linearly with the number of atoms, as we show with near-exact
      minimal basis set calculations with up to 1000 atoms. The linear scaling comes
      from both the localization of the basis and a compression method for the long
      ranged two-electron interaction. For shorter hydrogen chains, we show results
      with up to triple-zeta bases.

PMID- 29341749
TI  - Towards Attosecond High-Energy Electron Bunches: Controlling Self-Injection in
      Laser-Wakefield Accelerators Through Plasma-Density Modulation.
AB  - Self-injection in a laser-plasma wakefield accelerator is usually achieved by
      increasing the laser intensity until the threshold for injection is exceeded.
      Alternatively, the velocity of the bubble accelerating structure can be
      controlled using plasma density ramps, reducing the electron velocity required
      for injection. We present a model describing self-injection in the short-bunch
      regime for arbitrary changes in the plasma density. We derive the threshold
      condition for injection due to a plasma density gradient, which is confirmed
      using particle-in-cell simulations that demonstrate injection of subfemtosecond
      bunches. It is shown that the bunch charge, bunch length, and separation of
      bunches in a bunch train can be controlled by tailoring the plasma density
      profile.

PMID- 29341750
TI  - In-Plane Propagation of Light in Transition Metal Dichalcogenide Monolayers:
      Optical Selection Rules.
AB  - The optical selection rules for interband transitions in WSe_{2}, WS_{2}, and
      MoSe_{2} transition metal dichalcogenide monolayers are investigated by
      polarization-resolved photoluminescence experiments with a signal collection from
      the sample edge. These measurements reveal a strong polarization dependence of
      the emission lines. We see clear signatures of the emitted light with the
      electric field oriented perpendicular to the monolayer plane, corresponding to an
      interband optical transition forbidden at normal incidence used in standard
      optical spectroscopy measurements. The experimental results are in agreement with
      the optical selection rules deduced from group theory analysis, highlighting the
      key role played by the different symmetries of the conduction and valence bands
      split by the spin-orbit interaction. These studies yield a direct determination
      of the bright-dark exciton splitting, for which we measure 40+/-1  meV and 55+/-2
      meV in WSe_{2} and WS_{2} monolayer, respectively.

PMID- 29341751
TI  - Entanglement in Nonunitary Quantum Critical Spin Chains.
AB  - Entanglement entropy has proven invaluable to our understanding of quantum
      criticality. It is natural to try to extend the concept to "nonunitary quantum
      mechanics," which has seen growing interest from areas as diverse as open quantum
      systems, noninteracting electronic disordered systems, or nonunitary conformal
      field theory (CFT). We propose and investigate such an extension here, by
      focusing on the case of one-dimensional quantum group symmetric or supergroup
      symmetric spin chains. We show that the consideration of left and right
      eigenstates combined with appropriate definitions of the trace leads to a natural
      definition of Renyi entropies in a large variety of models. We interpret this
      definition geometrically in terms of related loop models and calculate the
      corresponding scaling in the conformal case. This allows us to distinguish the
      role of the central charge and effective central charge in rational minimal
      models of CFT, and to define an effective central charge in other, less well
      understood cases. The example of the sl(2|1) alternating spin chain for
      percolation is discussed in detail.

PMID- 29341752
TI  - Tensor-Network Simulations of the Surface Code under Realistic Noise.
AB  - The surface code is a many-body quantum system, and simulating it in generic
      conditions is computationally hard. While the surface code is believed to have a
      high threshold, the numerical simulations used to establish this threshold are
      based on simplified noise models. We present a tensor-network algorithm for
      simulating error correction with the surface code under arbitrary local noise. We
      use this algorithm to study the threshold and the subthreshold behavior of the
      amplitude damping and systematic rotation channels. We also compare these results
      to those obtained by making standard approximations to the noise models.

PMID- 29341753
TI  - Probing the Nano-Skyrmion Lattice on Fe/Ir(111) with Magnetic Exchange Force
      Microscopy.
AB  - We demonstrate that the magnetic nano-Skyrmion lattice on the Fe monolayer on
      Ir(111) and the positions of the Fe atoms can be resolved simultaneously using
      magnetic exchange force microscopy. Thus, the relation between magnetic and
      atomic structure can be determined straightforwardly by evaluating the Fourier
      transformation of the real space image data. We further show that the magnetic
      contrast can be mapped on a Heisenberg-like magnetic interaction between tip and
      sample spins. Since our imaging technique is based on measuring forces, our
      observation paves the way to study Skyrmions or other complex spin textures on
      insulating sample systems with atomic resolution.

PMID- 29341754
TI  - Plasma versus Drude Modeling of the Casimir Force: Beyond the Proximity Force
      Approximation.
AB  - We calculate the Casimir force and its gradient between a spherical and a planar
      gold surface. Significant numerical improvements allow us to extend the range of
      accessible parameters into the experimental regime. We compare our numerically
      exact results with those obtained within the proximity force approximation (PFA)
      employed in the analysis of all Casimir force experiments reported in the
      literature so far. Special attention is paid to the difference between the Drude
      model and the dissipationless plasma model at zero frequency. It is found that
      the correction to PFA is too small to explain the discrepancy between the
      experimental data and the PFA result based on the Drude model. However, it turns
      out that for the plasma model, the corrections to PFA lie well outside the
      experimental bound obtained by probing the variation of the force gradient with
      the sphere radius [D. E. Krause et al., Phys. Rev. Lett. 98, 050403
      (2007)PRLTAO0031-900710.1103/PhysRevLett.98.050403]. The corresponding
      corrections based on the Drude model are significantly smaller but still in
      violation of the experimental bound for small distances between plane and sphere.

PMID- 29341755
TI  - Excitation and Control of Plasma Wakefields by Multiple Laser Pulses.
AB  - We demonstrate experimentally the resonant excitation of plasma waves by trains
      of laser pulses. We also take an important first step to achieving an energy
      recovery plasma accelerator by showing that a plasma wave can be damped by an out
      of-resonance trailing laser pulse. The measured laser wakefields are found to be
      in excellent agreement with analytical and numerical models of wakefield
      excitation in the linear regime. Our results indicate a promising direction for
      achieving highly controlled, GeV-scale laser-plasma accelerators operating at
      multikilohertz repetition rates.

PMID- 29341756
TI  - Generic Theory for Majorana Zero Modes in 2D Superconductors.
AB  - It is well known that non-Abelian Majorana zero modes (MZM) are located at vortex
      cores in a p_{x}+??p_{y} topological superconductor, which can be realized in a
      2D spin-orbit coupled system with a single Fermi surface and by proximity
      coupling to an s-wave superconductor. Here we show that the existence of non
      Abelian MZMs is unrelated to the bulk topology of a 2D superconductor, and
      propose that such exotic modes can result in a much broader range of
      superconductors, being topological or trivial. For a generic 2D system with
      multiple Fermi surfaces that is gapped out by superconducting pairings, we show
      that at least a single MZM survives if there are only an odd number of Fermi
      surfaces of which the corresponding superconducting orders have vortices; such a
      MZM is protected by an emergent Chern-Simons invariant, irrespective of the bulk
      topology of the superconductor. This result enriches new experimental schemes for
      realizing non-Abelian MZMs. In particular, we propose a minimal scheme to realize
      the MZMs in a 2D superconducting Dirac semimetal with trivial bulk topology,
      which can be well achieved based on recent cold-atom experiments.

PMID- 29341757
TI  - Deconstructing Temperature Gradients across Fluid Interfaces: The Structural
      Origin of the Thermal Resistance of Liquid-Vapor Interfaces.
AB  - The interfacial thermal resistance determines condensation-evaporation processes
      and thermal transport across material-fluid interfaces. Despite its importance in
      transport processes, the interfacial structure responsible for the thermal
      resistance is still unknown. By combining nonequilibrium molecular dynamics
      simulations and interfacial analyses that remove the interfacial thermal
      fluctuations we show that the thermal resistance of liquid-vapor interfaces is
      connected to a low density fluid layer that is adsorbed at the liquid surface.
      This thermal resistance layer (TRL) defines the boundary where the thermal
      transport mechanism changes from that of gases (ballistic) to that characteristic
      of dense liquids, dominated by frequent particle collisions involving very short
      mean free paths. We show that the thermal conductance is proportional to the
      number of atoms adsorbed in the TRL, and hence we explain the structural origin
      of the thermal resistance in liquid-vapor interfaces.

PMID- 29341758
TI  - Nonreciprocal Magnons and Symmetry-Breaking in the Noncentrosymmetric
      Antiferromagnet.
AB  - Inelastic neutron scattering measurements were performed to study spin dynamics
      in the noncentrosymmetric antiferromagnet alpha-Cu_{2}V_{2}O_{7}. For the first
      time, nonreciprocal magnons were experimentally measured in an antiferromagnet.
      These nonreciprocal magnons are caused by the incompatibility between anisotropic
      exchange and antisymmetric Dzyaloshinskii-Moriya interactions, which arise from
      broken symmetry, resulting in a collinear ordered state but helical spin
      dynamics. The nonreciprocity introduces the difference in the phase velocity of
      the counterrotating modes, causing the opposite spontaneous magnonic Faraday
      rotation of the left- and right-propagating spin waves. The breaking of spatial
      inversion and time reversal symmetry is revealed as a magnetic-field-induced
      asymmetric energy shift, which provides a test for the detailed balance relation.

PMID- 29341759
TI  - Crossover from Classical to Fermi Liquid Behavior in Dense Plasmas.
AB  - We explore the crossover from classical plasma to quantum Fermi liquid behavior
      of electrons in dense plasmas. To this end, we analyze the evolution with density
      and temperature of the momentum lifetime of a test electron introduced in a dense
      electron gas. This allows us (1) to determine the boundaries of the crossover
      region in the temperature-density plane and to shed light on the evolution of
      scattering properties across it, (2) to quantify the role of the fermionic nature
      of electrons on electronic collisions across the crossover region, and (3) to
      explain how the concept of the Coulomb logarithm emerges at a high enough
      temperature but disappears at a low enough temperature.

PMID- 29341760
TI  - Correlated Photon Dynamics in Dissipative Rydberg Media.
AB  - Rydberg blockade physics in optically dense atomic media under the conditions of
      electromagnetically induced transparency (EIT) leads to strong dissipative
      interactions between single photons. We introduce a new approach to analyzing
      this challenging many-body problem in the limit of a large optical depth per
      blockade radius. In our approach, we separate the single-polariton EIT physics
      from Rydberg-Rydberg interactions in a serialized manner while using a hard
      sphere model for the latter, thus capturing the dualistic particle-wave nature of
      light as it manifests itself in dissipative Rydberg-EIT media. Using this
      approach, we analyze the saturation behavior of the transmission through one
      dimensional Rydberg-EIT media in the regime of nonperturbative dissipative
      interactions relevant to current experiments. Our model is able to capture the
      many-body dynamics of bright, coherent pulses through these strongly interacting
      media. We compare our model with available experimental data in this regime and
      find good agreement. We also analyze a scheme for generating regular trains of
      single photons from continuous-wave input and derive its scaling behavior in the
      presence of imperfect single-photon EIT.

PMID- 29341761
TI  - Superadditivity of the Classical Capacity with Limited Entanglement Assistance.
AB  - Finding the optimal encoding strategies can be challenging for communication
      using quantum channels, as classical and quantum capacities may be superadditive.
      Entanglement assistance can often simplify this task, as the entanglement
      assisted classical capacity for any channel is additive, making entanglement
      across channel uses unnecessary. If the entanglement assistance is limited, the
      picture is much more unclear. Suppose the classical capacity is superadditive,
      then the classical capacity with limited entanglement assistance could retain
      superadditivity by continuity arguments. If the classical capacity is additive,
      it is unknown if superadditivity can still be developed with limited entanglement
      assistance. We show this is possible, by providing an example. We construct a
      channel for which the classical capacity is additive, but that with limited
      entanglement assistance can be superadditive. This shows entanglement plays a
      weird role in communication, and we still understand very little about it.

PMID- 29341763
TI  - Auxiliary-Field Monte Carlo Method to Tackle Strong Interactions and Frustration
      in Lattice Bosons.
AB  - We introduce a new numerical technique, the bosonic auxiliary-field Monte Carlo
      method, which allows us to calculate the thermal properties of large lattice
      boson systems within a systematically improvable semiclassical approach, and
      which is virtually applicable to any bosonic model. Our method amounts to a
      decomposition of the lattice into clusters, and to an ansatz for the density
      matrix of the system in the form of a cluster-separable state-with nonentangled,
      yet classically correlated clusters. This approximation eliminates any sign
      problem, and can be systematically improved upon by using clusters of growing
      size. Extrapolation in the cluster size allows us to reproduce numerically exact
      results for the superfluid transition of hard-core bosons on the square lattice,
      and to provide a solid quantitative prediction for the superfluid and chiral
      transition of hardcore bosons on the frustrated triangular lattice.

PMID- 29341764
TI  - Order by Quenched Disorder in the Model Triangular Antiferromagnet
      RbFe(MoO_{4})_{2}.
AB  - We observe a disappearance of the 1/3 magnetization plateau and a striking change
      of the magnetic configuration under a moderate doping of the model triangular
      antiferromagnet RbFe(MoO_{4})_{2}. The reason is an effective lifting of
      degeneracy of mean-field ground states by a random potential of impurities, which
      compensates, in the low-temperature limit, the fluctuation contribution to free
      energy. These results provide a direct experimental confirmation of the
      fluctuation origin of the ground state in a real frustrated system. The change of
      the ground state to a least collinear configuration reveals an effective positive
      biquadratic exchange provided by the structural disorder. On heating, doped
      samples regain the structure of a pure compound, thus allowing for an
      investigation of the remarkable competition between thermal and structural
      disorder.

PMID- 29341765
TI  - Magnetic Fluctuations, Precursor Phenomena, and Phase Transition in MnSi under a
      Magnetic Field.
AB  - The reference chiral helimagnet MnSi is the first system where Skyrmion lattice
      correlations have been reported. At a zero magnetic field the transition at T_{C}
      to the helimagnetic state is of first order. Above T_{C}, in a region dominated
      by precursor phenomena, neutron scattering shows the buildup of strong chiral
      fluctuating correlations over the surface of a sphere with radius 2pi/l, where l
      is the pitch of the helix. It has been suggested that these fluctuating
      correlations drive the helical transition to first order following a scenario
      proposed by Brazovskii for liquid crystals. We present a comprehensive neutron
      scattering study under magnetic fields, which provides evidence that this is not
      the case. The sharp first order transition persists for magnetic fields up to 0.4
      T whereas the fluctuating correlations weaken and start to concentrate along the
      field direction already above 0.2 T. Our results thus disconnect the first order
      nature of the transition from the precursor fluctuating correlations. They also
      show no indication for a tricritical point, where the first order transition
      crosses over to second order with increasing magnetic field. In this light, the
      nature of the first order helical transition and the precursor phenomena above
      T_{C}, both of general relevance to chiral magnetism, remain an open question.

PMID- 29341766
TI  - Noise-Induced Subdiffusion in Strongly Localized Quantum Systems.
AB  - We consider the dynamics of strongly localized systems subject to dephasing noise
      with arbitrary correlation time. Although noise inevitably induces
      delocalization, transport in the noise-induced delocalized phase is subdiffusive
      in a parametrically large intermediate-time window. We argue for this
      intermediate-time subdiffusive regime both analytically and using numerical
      simulations on single-particle localized systems. Furthermore, we show that
      normal diffusion is restored in the long-time limit, through processes analogous
      to variable-range hopping. With numerical simulations based on Lanczos exact
      diagonalization, we demonstrate that our qualitative conclusions are also valid
      for interacting systems in the many-body localized phase.

PMID- 29341767
TI  - Dynamics of Dwarf Galaxies Disfavor Stellar-Mass Black Holes as Dark Matter.
AB  - We study the effects of black hole dark matter on the dynamical evolution of
      stars in dwarf galaxies. We find that mass segregation leads to a depletion of
      stars in the center of dwarf galaxies and the appearance of a ring in the
      projected stellar surface density profile. Using Segue 1 as an example we show
      that current observations of the projected surface stellar density rule out at
      the 99.9% confidence level the possibility that more than 6% of the dark matter
      is composed of black holes with a mass of few tens of solar masses.

PMID- 29341768
TI  - Novel Role of Superfluidity in Low-Energy Nuclear Reactions.
AB  - We demonstrate, within symmetry unrestricted time-dependent density functional
      theory, the existence of new effects in low-energy nuclear reactions which
      originate from superfluidity. The dynamics of the pairing field induces solitonic
      excitations in the colliding nuclear systems, leading to qualitative changes in
      the reaction dynamics. The solitonic excitation prevents collective energy
      dissipation and effectively suppresses the fusion cross section. We demonstrate
      how the variations of the total kinetic energy of the fragments can be traced
      back to the energy stored in the superfluid junction of colliding nuclei. Both
      contact time and scattering angle in noncentral collisions are significantly
      affected. The modification of the fusion cross section and possibilities for its
      experimental detection are discussed.

PMID- 29341769
TI  - Defect Structure of Localized Excitons in a WSe_{2} Monolayer.
AB  - The atomic and electronic structure of intrinsic defects in a WSe_{2} monolayer
      grown on graphite was revealed by low temperature scanning tunneling microscopy
      and spectroscopy. Instead of chalcogen vacancies that prevail in other transition
      metal dichalcogenide materials, intrinsic defects in WSe_{2} arise surprisingly
      from single tungsten vacancies, leading to the hole (p-type) doping. Furthermore,
      we found these defects to dominate the excitonic emission of the WSe_{2}
      monolayer at low temperature. Our work provided the first atomic-scale
      understanding of defect excitons and paved the way toward deciphering the defect
      structure of single quantum emitters previously discovered in the WSe_{2}
      monolayer.

PMID- 29341771
TI  - Quantum Numbers of Recently Discovered Omega_{c}^{0} Baryons from Lattice QCD.
AB  - We present the ground and excited state spectra of Omega_{c}^{0} baryons with
      spin up to 7/2 from lattice quantum chromodynamics with dynamical quark fields.
      Based on our lattice results, we predict the quantum numbers of five
      Omega_{c}^{0} baryons, which have recently been observed by the LHCb
      Collaboration. Our results strongly indicate that the observed states
      Omega_{c}(3000)^{0} and Omega_{c}(3050)^{0} have spin-parity J^{P}=1/2^{-}, the
      states Omega_{c}(3066)^{0} and Omega_{c}(3090)^{0} have J^{P}=3/2^{-}, whereas
      Omega_{c}(3119)^{0} is possibly a 5/2^{-} state.

PMID- 29341772
TI  - Determinant Diagrammatic Monte Carlo Algorithm in the Thermodynamic Limit.
AB  - We present a simple trick that allows us to consider the sum of all connected
      Feynman diagrams at fixed position of interaction vertices for general fermionic
      models, such that the thermodynamic limit can be taken analytically. With our
      approach one can achieve superior performance compared to conventional
      diagrammatic Monte Carlo algorithm, while rendering the algorithmic part
      dramatically simpler. By considering the sum of all connected diagrams at once,
      we allow for massive cancellations between different diagrams, greatly reducing
      the sign problem. In the end, the computational effort increases only
      exponentially with the order of the expansion, which should be contrasted with
      the factorial growth of the standard diagrammatic technique. We illustrate the
      efficiency of the technique for the two-dimensional Fermi-Hubbard model.

PMID- 29341773
TI  - Collective Optomechanical Effects in Cavity Quantum Electrodynamics.
AB  - We investigate a cavity quantum electrodynamic effect, where the alignment of two
      dimensional freely rotating optical dipoles is driven by their collective
      coupling to the cavity field. By exploiting the formal equivalence of a set of
      rotating dipoles with a polymer we calculate the partition function of the
      coupled light-matter system and demonstrate that it exhibits a second order phase
      transition between a bunched state of isotropic orientations and a stretched one
      with all the dipoles aligned. Such a transition manifests itself as an intensity
      dependent shift of the polariton mode resonance. Our work, lying at the crossroad
      between cavity quantum electrodynamics and quantum optomechanics, is a step
      forward in the ongoing quest to understand how strong coupling can be exploited
      to influence matter internal degrees of freedom.

PMID- 29341774
TI  - Tailoring Correlations of the Local Density of States in Disordered Photonic
      Materials.
AB  - We present experimental evidence for the different mechanisms driving the
      fluctuations of the local density of states (LDOS) in disordered photonic
      systems. We establish a clear link between the microscopic structure of the
      material and the frequency correlation function of LDOS accessed by a near-field
      hyperspectral imaging technique. We show, in particular, that short- and long
      range frequency correlations of LDOS are controlled by different physical
      processes (multiple or single scattering processes, respectively) that can be-to
      some extent-manipulated independently. We also demonstrate that the single
      scattering contribution to LDOS fluctuations is sensitive to subwavelength
      features of the material and, in particular, to the correlation length of its
      dielectric function. Our work paves a way towards complete control of statistical
      properties of disordered photonic systems, allowing for designing materials with
      predefined correlations of LDOS.

PMID- 29341775
TI  - Mixing by Unstirring: Hyperuniform Dispersion of Interacting Particles upon
      Chaotic Advection.
AB  - We show how to achieve both fast and hyperuniform dispersions of particles in
      viscous fluids. To do so, we first extend the concept of critical random
      organization to chaotic drives. We show how palindromic sequences of chaotic
      advection cause microscopic particles to effectively interact at long range,
      thereby inhibiting critical self-organization. Based on this understanding we go
      around this limitation and design sequences of stirring and unstirring which
      simultaneously optimize the speed of particle spreading and the homogeneity of
      the resulting dispersions.

PMID- 29341770
TI  - Search for Neutrinoless Quadruple-beta Decay of ^{150}Nd with the NEMO-3
      Detector.
AB  - We report the results of a first experimental search for lepton number violation
      by four units in the neutrinoless quadruple-beta decay of ^{150}Nd using a total
      exposure of 0.19 kg yr recorded with the NEMO-3 detector at the Modane
      Underground Laboratory. We find no evidence of this decay and set lower limits on
      the half-life in the range T_{1/2}>(1.1-3.2)*10^{21}  yr at the 90% C.L.,
      depending on the model used for the kinematic distributions of the emitted
      electrons.

PMID- 29341776
TI  - Magnetic Domain Walls as Hosts of Spin Superfluids and Generators of Skyrmions.
AB  - A domain wall in a magnet with easy-axis anisotropy is shown to harbor spin
      superfluid associated with its spontaneous breaking of the U(1) spin-rotational
      symmetry. The spin superfluid is shown to have several topological properties,
      which are absent in conventional superfluids. First, the associated phase slips
      create and destroy Skyrmions to obey the conservation of the total Skyrmion
      charge, which allows us to use a domain wall as a generator and detector of
      Skyrmions. Second, the domain wall engenders the emergent magnetic flux for
      magnons along its length, which are proportional to the spin supercurrent flowing
      through it, and thereby provides a way to manipulate magnons. Third, the spin
      supercurrent can be driven by the magnon current traveling across it owing to the
      spin transfer between the domain wall and magnons, leading to the magnonic
      manipulation of the spin superfluid. The theory for superfluid spin transport
      within the domain wall is confirmed by numerical simulations.

PMID- 29341777
TI  - High-Fidelity Single-Shot Singlet-Triplet Readout of Precision-Placed Donors in
      Silicon.
AB  - In this work we perform direct single-shot readout of the singlet-triplet states
      in exchange coupled electrons confined to precision-placed donor atoms in
      silicon. Our method takes advantage of the large energy splitting given by the
      Pauli-spin blockaded (2,0) triplet states, from which we can achieve a single
      shot readout fidelity of 98.4+/-0.2%. We measure the triplet-minus relaxation
      time to be of the order 3 s at 2.5 T and observe its predicted decrease as a
      function of magnetic field, reaching 0.5 s at 1 T.

PMID- 29341778
TI  - Entanglement-Enhanced Radio-Frequency Field Detection and Waveform Sensing.
AB  - We demonstrate a new technique for detecting the amplitude of arbitrarily chosen
      components of radio-frequency waveforms based on stroboscopic backaction evading
      measurements. We combine quantum nondemolition measurements and stroboscopic
      probing to detect waveform components with magnetic sensitivity beyond the
      standard quantum limit. Using an ensemble of 1.5*10^{6} cold rubidium atoms, we
      demonstrate entanglement-enhanced sensing of sinusoidal and linearly chirped
      waveforms, with 1.0(2) and 0.8(3) dB metrologically relevant noise reduction,
      respectively. We achieve volume-adjusted sensitivity of deltaBsqrt[V]~3.96 
      fTsqrt[cm^{3}/Hz], comparable to the best rf magnetometers.

PMID- 29341779
TI  - Mesoscopic Transport in Electrostatically Defined Spin-Full Channels in Quantum
      Hall Ferromagnets.
AB  - In this work, we use electrostatic control of quantum Hall ferromagnetic
      transitions in CdMnTe quantum wells to study electron transport through
      individual domain walls (DWs) induced at a specific location. These DWs are
      formed due to the hybridization of two counterpropagating edge states with
      opposite spin polarization. Conduction through DWs is found to be symmetric under
      magnetic field direction reversal, consistent with the helical nature of these
      DWs. We observe that long domain walls are in the insulating regime with a
      localization length of 4-6  MUm. In shorter DWs, the resistance saturates to a
      nonzero value at low temperatures. Mesoscopic resistance fluctuations in a
      magnetic field are investigated. The theoretical model of transport through
      impurity states within the gap induced by spin-orbit interactions agrees well
      with the experimental data. Helical DWs have the required symmetry for the
      formation of synthetic p-wave superconductors. The achieved electrostatic control
      of a single helical domain wall is a milestone on the path to their
      reconfigurable network and ultimately to a demonstration of the braiding of non
      Abelian excitations.

PMID- 29341780
TI  - Interplay of Correlations and Kohn Anomalies in Three Dimensions: Quantum
      Criticality with a Twist.
AB  - A general understanding of quantum phase transitions in strongly correlated
      materials is still lacking. By exploiting a cutting-edge quantum many-body
      approach, the dynamical vertex approximation, we make important progress,
      determining the quantum critical properties of the antiferromagnetic transition
      in the fundamental model for correlated electrons, the Hubbard model in three
      dimensions. In particular, we demonstrate that-in contradiction to the
      conventional Hertz-Millis-Moriya theory-its quantum critical behavior is driven
      by the Kohn anomalies of the Fermi surface, even when electronic correlations
      become strong.

PMID- 29341781
TI  - Valley-Polarized Quantum Anomalous Hall Effect in Ferrimagnetic Honeycomb
      Lattices.
AB  - The valley-polarized quantum anomalous Hall effect (VP-QAHE), which combines
      valleytronics and topology in one material, is of significant fundamental and
      practical importance in condensed-matter physics and materials science. In
      previous model studies, VP-QAHE occurs under strong Rashba spin-orbit coupling
      (SOC), which is an extrinsic effect. Here, using a low energy k.p model, we
      propose a different mechanism of VP-QAHE by introducing an intrinsic staggered
      magnetic exchange field and develop a general picture of valley dependent band
      inversion in honeycomb lattice. Using first-principles calculation, this new
      mechanism is further demonstrated in the Co decorated In-triangle adlayer on a
      Si(111) surface. This system is equivalent to a ferrimagnetic honeycomb lattice,
      and the supported adlayer is experimentally more feasible in synthesis, thus
      exhibiting advantages over the existing studies based on Rashba SOC and free
      standing sheets. The underlying physical mechanism is generally applicable,
      opening a new avenue for exploration of substrate supported VP-QAHE.

PMID- 29341782
TI  - Complex Quasi-Two-Dimensional Crystalline Order Embedded in VO_{2} and Other
      Crystals.
AB  - Metal oxides such as VO_{2} undergo structural transitions to low-symmetry phases
      characterized by intricate crystalline order, accompanied by rich electronic
      behavior. We derive a minimal ionic Hamiltonian based on symmetry and local
      energetics which describes structural transitions involving all four observed
      phases, in the correct order. An exact analysis shows that complexity results
      from the symmetry-induced constraints of the parent phase, which forces ionic
      displacements to form multiple interpenetrating groups using low-dimensional
      pathways and distant neighbors. Displacements within each group exhibit
      independent, quasi-two-dimensional order, which is frustrated and fragile. This
      selective ordering mechanism is not restricted to VO_{2}: it applies to other
      oxides that show similar complex order.

PMID- 29341783
TI  - Bell Inequalities Tailored to Maximally Entangled States.
AB  - Bell inequalities have traditionally been used to demonstrate that quantum theory
      is nonlocal, in the sense that there exist correlations generated from composite
      quantum states that cannot be explained by means of local hidden variables. With
      the advent of device-independent quantum information protocols, Bell inequalities
      have gained an additional role as certificates of relevant quantum properties. In
      this work, we consider the problem of designing Bell inequalities that are
      tailored to detect maximally entangled states. We introduce a class of Bell
      inequalities valid for an arbitrary number of measurements and results, derive
      analytically their tight classical, nonsignaling, and quantum bounds and prove
      that the latter is attained by maximally entangled states. Our inequalities can
      therefore find an application in device-independent protocols requiring maximally
      entangled states.

PMID- 29341784
TI  - Fractional Transport in Strongly Turbulent Plasmas.
AB  - We analyze statistically the energization of particles in a large scale
      environment of strong turbulence that is fragmented into a large number of
      distributed current filaments. The turbulent environment is generated through
      strongly perturbed, 3D, resistive magnetohydrodynamics simulations, and it
      emerges naturally from the nonlinear evolution, without a specific reconnection
      geometry being set up. Based on test-particle simulations, we estimate the
      transport coefficients in energy space for use in the classical Fokker-Planck
      (FP) equation, and we show that the latter fails to reproduce the simulation
      results. The reason is that transport in energy space is highly anomalous
      (strange), the particles perform Levy flights, and the energy distributions show
      extended power-law tails. Newly then, we motivate the use and derive the specific
      form of a fractional transport equation (FTE), we determine its parameters and
      the order of the fractional derivatives from the simulation data, and we show
      that the FTE is able to reproduce the high energy part of the simulation data
      very well. The procedure for determining the FTE parameters also makes clear that
      it is the analysis of the simulation data that allows us to make the decision
      whether a classical FP equation or a FTE is appropriate.

PMID- 29341785
TI  - Total sleep deprivation does not significantly degrade semantic encoding.
AB  - Sleep deprivation impairs performance on cognitive tasks, but it is unclear which
      cognitive processes it degrades. We administered a semantic matching task with
      variable stimulus onset asynchrony (SOA) and both speeded and self-paced trial
      blocks. The task was administered at the baseline and 24 hours later after 30.8
      hours of total sleep deprivation (TSD) or matching well-rested control. After
      sleep deprivation, the 20% slowest response times (RTs) were significantly
      increased. However, the semantic encoding time component of the RTs remained at
      baseline level. Thus, the performance impairment induced by sleep deprivation on
      this task occurred in cognitive processes downstream of semantic encoding.

PMID- 29341786
TI  - Unscheduled adolescents return to the emergency department following acute
      concussion.
AB  - OBJECTIVE: Emergency department (ED) visits due to concussion have increased over
      recent years. We aimed to identify variables associated with unscheduled
      adolescents return to the ED. METHODS: A retrospective cohort study was
      conducted. All children aged 11 to 18 years who were admitted to the ED due to
      concussion between 2011 and 2016 were included. Multivariable logistic regression
      was performed to identify predictors of ED return. RESULTS: Overall, 616
      adolescents were admitted to the ED due to concussion. Within the first week from
      discharge, 37/616 (6%) patients returned unscheduled to the ED, 21 (3.4%) during
      the first 48 hours and 16 (2.6%) during the following 3-7 days. Age, gender,
      ethnicity, diagnosis of concussion on first visit and length-of-stay in the ED
      were not associated with unscheduled ED returns. Variables that were
      independently associated with increased odds for an unscheduled ED return
      included two or more symptoms of concussion [odds ratio (OR): 2.81; 95%
      confidence interval (CI): (1.16-6.82)], bicycle or motor vehicle accident (OR:
      3.48; 95% CI: 1.29-9.4), and performance of CT scan on first visit (OR: 2.47; 95%
      CI: 1.12-5.48). CONCLUSIONS: The findings suggest that certain variables on the
      first ED visit can predict an unscheduled return visit in adolescents.
      ABBREVIATIONS: Emergency department (ED); Length of stay (LOS); computerised
      tomography (CT).

PMID- 29341787
TI  - The effects of early life polyunsaturated fatty acids and ruminant trans fatty
      acids on allergic diseases: A systematic review and meta-analysis.
AB  - Early life nutritional exposures could modify the gene expression and
      susceptibility of allergic diseases (AD). This systematic review aimed to
      evaluate whether early life (the first 1,000 days) natural exposure to
      polyunsaturated fatty acids (PUFA) and ruminant trans fatty acids (R-TFA) could
      affect the AD risk. We searched PubMed, EMBASE, PsycINFO, Scopus, the Cochrane
      Library, and ClinicalTrials.gov from inception through September 10, 2017 for
      relevant full-text articles in English. Observational studies were selected if
      they examined the effects of early life PUFA or R-TFA on AD (eczema, asthma,
      wheeze, and allergic rhinitis) or sensitization. The quality of studies was
      examined by the Newcastle-Ottawa Scale, and the best evidence synthesis (BES) was
      applied. We included 26 observational studies, and 8 of them showed high quality.
      BES showed a moderate evidence for the protective effect of vaccenic acid (VA, an
      R-TFA) on eczema, while insufficient or no evidence was found in other
      associations. Meta-analysis showed that higher n-6/n-3 ratio and linoleic acid
      were associated with higher risk of eczema (pooled odds ratio [OR] = 1.06, 95%
      confidence intervals [CI]: 1.00 -1.13; 1.08, 95% CI: 1.01 -1.15). However, VA was
      inversely associated with eczema pooled OR = 0.42, 95% CI: 0.25 -0.72). Early
      life natural exposure to VA showed evident benefit on decreasing the risk of
      eczema, while PUFA and other R-TFA showed limited effects on AD. More robust
      studies especially for R-TFA are required.

PMID- 29341788
TI  - Specific airway resistance is a better outcome parameter in bronchial provocation
      testing compared to FEV1 in patients with bronchial asthma.
AB  - OBJECTIVES: Asthma is a chronic inflammatory disease characterized by airway
      hyperresponsiveness (AHR). A bronchial provocation test (BPT) is used to test for
      AHR. However forced expiratory volume in one second (FEV1), used as outcome
      parameter is effort-related, in contrast to specific airway resistance (sRaw).
      This research was conducted to provide insight in the usefulness of sRaw as an
      outcome parameter in BPT. METHODS: A total of 85 patients performing a BPT were
      included in the study. Bronchial reactivity was defined as the provocative dosage
      or provocative concentration causing a 20% decrease in FEV1 (PC-20) or a 100%
      increase in sRaw (PC+100). RESULTS: No significant response in either FEV1 or
      sRaw was found in 20 patients (24%). Twenty-nine patients (34%) only had a
      positive response for sRaw; 24 out of these 29 patients recognized their
      symptoms. 36 patients (42%) showed a positive response for both PC-20 and PC +
      100. CONCLUSIONS: Twenty-nine patients (34%) showed a significant increase in
      sRaw without a fall in FEV1. As performing sRaw is not a routine investigation,
      these patients are at risk of being excluded from a diagnosis of asthma. We
      suggest performing sRaw for patients without a fall in FEV1 during BPT when they
      report recognizable symptoms.

PMID- 29341789
TI  - Psychometric properties of the Epworth Sleepiness Scale: A factor analysis and
      item-response theory approach.
AB  - The purpose of this study is to examine the psychometric properties of the
      Epworth Sleepiness Scale (ESS) in two languages, German and English. Students
      from a university in Austria (N = 292; 55 males; mean age = 18.71 +/- 1.71 years;
      237 females; mean age = 18.24 +/- 0.88 years) and a university in the US (N =
      329; 128 males; mean age = 18.71 +/- 0.88 years; 201 females; mean age = 21.59 +/
      2.27 years) completed the ESS. An exploratory-factor analysis was completed to
      examine dimensionality of the ESS. Item response theory (IRT) analyses were used
      to provide information about the response rates on the items on the ESS and
      provide differential item functioning (DIF) analyses to examine whether the items
      were interpreted differently between the two languages. The factor analyses
      suggest that the ESS measures two distinct sleepiness constructs. These
      constructs indicate that the ESS is probing sleepiness in settings requiring
      active versus passive responding. The IRT analyses found that overall, the items
      on the ESS perform well as a measure of sleepiness. However, Item 8 and to a
      lesser extent Item 6 were being interpreted differently by respondents in
      comparison to the other items. In addition, the DIF analyses showed that the
      responses between German and English were very similar indicating that there are
      only minor measurement differences between the two language versions of the ESS.
      These findings suggest that the ESS provides a reliable measure of propensity to
      sleepiness; however, it does convey a two-factor approach to sleepiness.
      Researchers and clinicians can use the German and English versions of the ESS but
      may wish to exclude Item 8 when calculating a total sleepiness score.

PMID- 29341791
TI  - Population level evidence for seasonality of the human microbiome.
AB  - The objective of this study is to determine whether human body odors undergo
      seasonal modulation. We utilized google trends search volume from the United
      States of America from January 1, 2010 to June 24, 2017 for a number of
      predetermined body odors. Regression modeling of time series data was completed.
      Our primary outcome was to determine the proportion of the variability in
      Internet searches for each unpleasant odor (about the mean) that is explained by
      a seasonal model. We determined that the seasonal (sinusoidal) model provided a
      significantly better fit than the null model (best straight line fit) for all
      searches relating to human body odors (P <.0001 for each). This effect was easily
      visible to the naked eye in the raw time series data. Seasonality explained 88%
      of the variability in search volume for flatulence (i.e. R2 = 0.88), 65% of the
      variability in search volume for axillary odor, 60% of the variability in search
      volume for foot odor, and 58% of the variability in search volume for bad breath.
      Flatulence and bad breath tended to peak in January, foot odor in February, and
      Axillary odor in July. We conclude that searching by the general public for
      information on unpleasant body odors undergoes substantial seasonal variation,
      with the timing of peaks and troughs varying with the body part involved. The
      symptom burden of such smells may have a similar seasonal variation, as might the
      composition of the commensal bacterial microflora that play a role in creating
      them.

PMID- 29341792
TI  - The blinding thyroid gland.

PMID- 29341790
TI  - Postnatal tendon growth and remodeling require platelet-derived growth factor
      receptor signaling.
AB  - Platelet-derived growth factor receptor (PDGFR) signaling plays an important role
      in the fundamental biological activities of many cells that compose
      musculoskeletal tissues. However, little is known about the role of PDGFR
      signaling during tendon growth and remodeling in adult animals. Using the
      hindlimb synergist ablation model of tendon growth, our objectives were to
      determine the role of PDGFR signaling in the adaptation of tendons subjected to a
      mechanical growth stimulus, as well as to investigate the biological mechanisms
      behind this response. We demonstrate that both PDGFRs, PDGFRalpha and PDGFRbeta,
      are expressed in tendon fibroblasts and that the inhibition of PDGFR signaling
      suppresses the normal growth of tendon tissue in response to mechanical growth
      cues due to defects in fibroblast proliferation and migration. We also identify
      membrane type-1 matrix metalloproteinase (MT1-MMP) as an essential proteinase for
      the migration of tendon fibroblasts through their extracellular matrix.
      Furthermore, we report that MT1-MMP translation is regulated by phosphoinositide
      3-kinase/Akt signaling, while ERK1/2 controls posttranslational trafficking of
      MT1-MMP to the plasma membrane of tendon fibroblasts. Taken together, these
      findings demonstrate that PDGFR signaling is necessary for postnatal tendon
      growth and remodeling and that MT1-MMP is a critical mediator of tendon
      fibroblast migration and a potential target for the treatment of tendon injuries
      and diseases.

PMID- 29341793
TI  - Platelet transfusion does not improve outcomes in patients with brain injury on
      antiplatelet therapy.
AB  - INTRODUCTION: Platelet dysfunction following traumatic brain injury (TBI) is
      associated with worse outcomes. The efficacy of platelet transfusion to reverse
      antiplatelet medication (APM) remains unknown. Thrombelastography platelet
      mapping (TEG-PM) assesses platelet function. We hypothesize that platelet
      transfusion can reverse the effects of APM but does not improve outcomes
      following TBI. METHODS: An observational study at six US trauma centres was
      performed. Adult patients on APM with CT evident TBI after blunt injury were
      enrolled. Demographics, brain CT and TEG-PM results before/after platelet
      transfusion, length of stay (LOS), and injury severity score (ISS) were
      abstracted. RESULTS: Sixty six patients were enrolled (89% aspirin, 50%
      clopidogrel, 23% dual APM) with 23 patients undergoing platelet transfusion.
      Transfused patients had significantly higher ISS and admission CT scores.
      Platelet transfusion significantly reduced platelet inhibition due to aspirin
      (76.0 +/- 30.2% to 52.7 +/- 31.5%, p < 0.01), but had a non-significant impact on
      clopidogrel-associated inhibition (p = 0.07). Platelet transfusion was associated
      with longer length of stay (7.8 vs. 3.5 days, p < 0.01), but there were no
      differences in mortality. CONCLUSION: Platelet transfusion significantly
      decreases platelet inhibition due to aspirin but is not associated with change in
      outcomes in patients on APM following TBI.

PMID- 29341794
TI  - Preseason Strength Assessment of the Rotator Muscles and Shoulder Injury in
      Handball Players.
AB  - CONTEXT:   Few researchers have identified intrinsic risk factors for shoulder
      injury in team handball players by analyzing measurements of maximal isokinetic
      rotator muscle strength. OBJECTIVE:   To identify possible intrinsic risk factors
      for shoulder injury by analyzing measurements of maximal isokinetic rotator
      muscle strength. DESIGN:   Cross-sectional study. SETTING:   Male team handball
      senior divisions (the highest level) in France and Belgium. PATIENTS OR OTHER
      PARTICIPANTS:   A total of 108 male high-level handball players (age = 24 +/- 4
      years, height = 189 +/- 6 cm, mass = 87 +/- 11 kg) were enrolled. MAIN OUTCOME
      MEASURE(S):   All players completed a preseason questionnaire and performed a
      bilateral isokinetic assessment of the shoulder rotator muscles. On a monthly
      questionnaire, players reported any shoulder injury that they sustained during
      the season. RESULTS:   On the preseason questionnaire, 51 of 108 (47%)
      participants reported a history of dominant-shoulder injury. A total of 106
      participants completed the in-season questionnaire, with 22% (n = 23) reporting a
      shoulder injury on their dominant side during the subsequent season. Fourteen
      percent (n = 15) sustained microtraumatic injuries, and 8% (n = 8) described a
      traumatic injury. Backcourt players had a 3.5-times increased risk of injury
      during the new season compared with players in other positions. Among the
      isokinetic results, no risk factor for further injury was identified in handball
      players with microtraumatic injuries. For traumatic injuries, the concentric
      maximal strength developed by the internal rotators at high speed (240 degrees
      /s) in the dominant shoulder was a protective factor against the risk of further
      injury. CONCLUSIONS:   These results can potentially identify intrinsic risk
      factors for shoulder injury and may be used to determine potential interventions
      for reducing this risk in handball players.

PMID- 29341762
TI  - First Observation of a Baryonic B_{s}^{0} Decay.
AB  - We report the first observation of a baryonic B_{s}^{0} decay, B_{s}^{0}
      >pLambda[over -]K^{-}, using proton-proton collision data recorded by the LHCb
      experiment at center-of-mass energies of 7 and 8 TeV, corresponding to an
      integrated luminosity of 3.0  fb^{-1}. The branching fraction is measured to be
      B(B_{s}^{0}->pLambda[over -]K^{-})+B(B_{s}^{0}->p[over -]LambdaK^{+})=[5.46+/
      0.61+/-0.57+/-0.50(B)+/-0.32(f_{s}/f_{d})]*10^{-6}, where the first uncertainty
      is statistical and the second systematic, the third uncertainty accounts for the
      experimental uncertainty on the branching fraction of the B^{0}->pLambda[over 
      ]pi^{-} decay used for normalization, and the fourth uncertainty relates to the
      knowledge of the ratio of b-quark hadronization probabilities f_{s}/f_{d}.

PMID- 29341795
TI  - The Ability to Provide Quality Chest Compressions Over Lacrosse Shoulder Pads.
AB  - CONTEXT:   Performance of quality cardiopulmonary resuscitation is essential for
      improving patient outcomes. Performing compressions over football equipment
      inhibits compression depth and rate, but lacrosse equipment has not yet been
      studied. OBJECTIVE:   To assess the effect of lacrosse shoulder pads on the
      ability to provide quality chest compressions on simulation manikins. DESIGN:  
      Crossover study. SETTING:   Simulation laboratory. PATIENTS OR OTHER
      PARTICIPANTS:   Thirty-six athletic trainers (12 men: age = 33.3 +/- 9.7 years;
      24 women: age = 33.4 +/- 9.8 years). MAIN OUTCOME MEASURE(S):   No shoulder pads
      (NSP), Warrior Burn Hitman shoulder pads (WSP), and STX Cell II shoulder pads
      (SSP) were investigated. Outcomes were chest-compression depth (millimeters),
      rate (compressions per minute), rating of perceived exertion (0-10), hand
      placement accuracy (%), and chest recoil (%). RESULTS:   We observed a difference
      in mean compression depth among shoulder-pad conditions ( F2,213 = 3.73, P = .03,
      omega2 = 0.03), with a shallower depth during the WSP (54.1 +/- 5.8 mm) than the
      NSP (56.8 +/- 5.7 mm; P = .02) trials. However, no differences were found in mean
      compression rate ( F2,213 = 0.87, P = .42, omega2 = 0.001, 1-beta = .20). We
      noted a difference in rating of perceived exertion scores ( F2,213 = 16.41, P <
      .001, omega2 = 0.12). Compressions were more difficult during the SSP condition
      (4.1 +/- 1.3) than during the NSP (2.9 +/- 1.2; P < .001) and WSP (3.3 +/- 1.1; P
      = .002) conditions. A difference was present in hand-placement accuracy among the
      3 shoulder-pad conditions (chi22 = 11.14, P = .004). Hand-placement accuracy was
      better in the NSP than the SSP condition ( P = .002) and the SSP than the WSP
      condition ( P = .001). CONCLUSIONS:   Lacrosse shoulder pads did not inhibit the
      ability to administer chest compressions with adequate rate and depth. With
      appropriate training to improve hand placement, the pads may be left in place
      while cardiopulmonary resuscitation is initiated during sudden cardiac arrest.

PMID- 29341796
TI  - Correction to: Missed medical appointments during shifts to and from daylight
      saving time.

PMID- 29341799
TI  - DIGEST.

PMID- 29341798
TI  - Phenolic Constituents and Inhibitory Effects of Hibiscus sabdariffa L. (Sorrel)
      Calyx on Cholinergic, Monoaminergic, and Purinergic Enzyme Activities.
AB  - This study revealed the effect of phenolic extract from Hibiscus sabdariffa L.
      (sorrel) calyx on acetylcholinesterase (AChE), butyrylcholinesterase (BChE),
      monoamine oxidase (MAO), and ecto-5' nucleotidase (E-NTDase) activities as well
      as pro-oxidant-induced oxidative damage in rat brain in vitro. Sorrel extract
      inhibited AChE (EC50 = 46.96 ug/mL), BChE (EC50 = 40.38 ug/mL), MAO (EC50 = 43.69
      ug/mL), and E-NTDase (EC50 = 40.52 ug/mL) and stimulated Na+/K+-ATPase (EC50 =
      22.01 ug/mL) activities. The phenolic extract also reduced Fe2+- (EC50 = 22.37
      ug/mL) and sodium nitroprusside- (SNP-) (21.46 ug/mL) induced malondialdehyde
      (MDA) production in rat brain homogenates. Catechin (53.12 mg/g), chlorogenic
      (67.12 mg/g), rutin (16.25 mg/g), and caffeic acid (15.38 mg/g) were the most
      abundant phenolic compounds in the extract. The synergistic effects of the
      phenolic compounds may contribute to the enzyme inhibitory and stimulatory
      activities of the extract. Our findings suggest that sorrel extract shows
      promising potential for the treatment and/or management of some neurodegenerative
      diseases such as Alzheimer's disease and Parkinson's disease.

PMID- 29341800
TI  - Factors Associated with Patient Satisfaction in an Outpatient Glaucoma
      Population.
AB  - PURPOSE: To determine what metrics might impact satisfaction survey responses.
      METHODS: A 37-question survey was administered to 249 participants. Responses
      were correlated to demographics, clinical factors, weather conditions, and
      examination timing. RESULTS: Sample consists of 55.4% female and 73.9% white, and
      mean age was 65.1 years. Participants were assigned to: completely satisfied
      (77.9%) or not completely satisfied (22.1%) groups based on their rating of
      glaucoma specialist on a scale of 1-10, while 10 considered "completely
      satisfied" and less than 10 "not completely satisfied." Complete satisfaction was
      associated with ability to schedule appointments early, phone calls
      answered/returned same day, shorter perceived wait time, and better communication
      skills of ophthalmologist (p < 0.05). Completely satisfied participants reported
      their ophthalmologist spent enough time with them, listened carefully, and
      communicated in an understandable way (p < 0.05). CONCLUSIONS: The majority of
      factors found to be associated with patient satisfaction were related to
      characteristics of the ophthalmologists and their office.

PMID- 29341797
TI  - Visual dependence affects postural sway responses to continuous visual field
      motion in individuals with cerebral palsy.
AB  - : The current study aimed to explore the impact of visual dependence on
      sensorimotor coupling of postural sway and visual motion in adults and teens with
      spastic cerebral palsy (CP). We hypothesized that individuals with CP would
      exhibit greater magnitudes of sway than healthy individuals, and the presence of
      visual dependence (VD) would produce instability in the direction of visual
      motion. Participants stood in a virtual environment in which the visual scene
      remained static or continuously rotated 30 degree/second in pitch-up or pitch
      down. Increased center of pressure and center of mass responses were observed in
      the direction of visual scene motion in those with CP. Those with VD exhibited
      reduced frequency responses in anterior-posterior direction than those who were
      visually independent. VD suggests deficient sensorimotor integration that could
      contribute to postural instability and reduced motor function. Individuals with
      CP who are visually dependent may benefit from more sensory focused
      rehabilitation strategies. ABBREVIATIONS: AP, anterior-posterior; CP, cerebral
      palsy; COM, center of mass; COP, center of pressure; MDF, median frequency; ML,
      mediolateral; PD, pitch down (nose down) rotation; PU, pitch up (nose up)
      rotation; RFT, rod and frame test; RMS, root mean square; SLP, slope of the
      fitted line; TD, typical development; VD, visual dependence; VI, visual
      independence; VOR, vestibulo-ocular reflex; VPI, visual perceptual impairment.

PMID- 29341801
TI  - Local vs. national: Epidemiology of pedestrian injury in a mid-Atlantic city.
AB  - OBJECTIVE: Understanding pedestrian injury trends at the local level is essential
      for program planning and allocation of funds for urban planning and improvement.
      Because we hypothesize that local injury trends differ from national trends in
      significant and meaningful ways, we investigated citywide pedestrian injury
      trends to assess injury risk among nationally identified risk groups, as well as
      identify risk groups and locations specific to Baltimore City. METHODS:
      Pedestrian injury data, obtained from the Baltimore City Fire Department, were
      gathered through emergency medical services (EMS) records collected from January
      1 to December 31, 2014. Locations of pedestrian injuries were geocoded and
      mapped. Pearson's chi-square test of independence was used to investigate
      differences in injury severity level across risk groups. Pedestrian injury rates
      by age group, gender, and race were compared to national rates. RESULTS: A total
      of 699 pedestrians were involved in motor vehicle crashes in 2014-an average of 2
      EMS transports each day. The distribution of injuries throughout the city did not
      coincide with population or income distributions, indicating that there was not a
      consistent correlation between areas of concentrated population or concentrated
      poverty and areas of concentrated pedestrian injury. Twenty percent (n = 138) of
      all injuries occurred among children age <=14, and 22% (n = 73) of severe
      injuries occurred among young children. The rate of injury in this age group was
      5 times the national rate (Incident Rate Ratio [IRR] = 4.81, 95% confidence
      interval [CI], [4.05, 5.71]). Injury rates for adults >=65 were less than the
      national average. CONCLUSIONS: As the urban landscape and associated pedestrian
      behavior transform, continued investigation of local pedestrian injury trends and
      evolving public health prevention strategies is necessary to ensure pedestrian
      safety.

PMID- 29341802
TI  - Portulaca oleracea L. Extract Enhances Glucose Uptake by Stimulating GLUT4
      Translocation to the Plasma Membrane in 3T3-L1 Adipocytes.
AB  - This study investigated the effects of Portulaca oleracea L. extract on glucose
      uptake in 3T3-L1 adipocytes. P. oleracea extract (POE) markedly enhanced glucose
      uptake, which was caused by increased GLUT4 expression at the plasma membrane
      (PM) in 3T3-L1 adipocytes. This increase in PM-GLUT4 expression was associated
      with insulin receptor substrate-1 (IRS-1) phosphorylation, phosphatidylinositol 3
      kinase (PI3K) activation, and Akt phosphorylation, and finally, enhanced
      intracellular glucose uptake. POE was not associated with protein kinase C
      (PKC)lambda/zeta phosphorylation in the insulin signaling pathway, but did
      promote 5'-AMP-activated kinase (AMPK) phosphorylation. Increased glucose uptake
      through POE was inhibited through treating with the PI3K inhibitor or AMPK
      inhibitor in 3T3-L1 adipocytes. This result suggested that POE may enhance
      glucose uptake by stimulating GLUT4 translocation to the PM through activating
      the PI3K and AMPK pathway in 3T3-L1 adipocytes.

PMID- 29341804
TI  - Benefits and logistics of nonpresenting undergraduate students attending a
      professional scientific meeting.

PMID- 29341803
TI  - Licorice Pretreatment Protects Against Brain Damage Induced by Middle Cerebral
      Artery Occlusion in Mice.
AB  - Licorice is extracted from the roots of plants in the Glycyrrhiza genus,
      especially Glycyrrhiza uralensis in China and Korea. It has several
      pharmacological activities, including neuro-protective, anti-fungal, and anti
      cariogenic effects. Ischemia/reperfusion-induced brain injury is a leading cause
      of adult disability and death; thus, the identification of anti-apoptotic, neuro
      protective therapeutic agents is viewed as an attractive drug development
      strategy. Infarct volumes and the expression of several apoptosis-related
      proteins, including Bcl-xL, Bcl-2, caspase-8, and caspase-9, were evaluated by
      western blotting in the brains of mice subjected to middle cerebral artery
      occlusion (MCAO). Three consecutive days of oral pretreatment with the methanol
      extract of licorice (GRex) significantly reduced infarct volumes 24 h after MCAO.
      In addition, GRex effectively inhibited the activation of caspase-9 by
      upregulating protein expression of Bcl-xL and Bcl-2. The neuro-protective effect
      of licorice was due to its regulation of apoptosis-related proteins. These data
      suggest that licorice could be a potential candidate for the treatment of
      ischemia-induced brain damage.

PMID- 29341805
TI  - A case study approach, combined with modified team-based learning, to teach the
      progression of metabolic syndrome to type 2 diabetes.

PMID- 29341806
TI  - The membrane potential puzzle: a new educational game to use in physiology
      teaching.

PMID- 29341807
TI  - Active memory reactivation previous to the introduction of a new related content
      improves students' learning.

PMID- 29341808
TI  - Development of an open-access, web-based interactive tool to learn autonomic
      nervous system physiology and pharmacology.

PMID- 29341809
TI  - Modified directed self-learning sessions in physiology with prereading
      assignments and Pecha Kucha talks: perceptions of students.
AB  - The present study reports perceptions of first-year undergraduate medical
      students ( n = 120), regarding modified directed self-learning (DSL) sessions in
      physiology. Students were provided with prereading assignments (faculty developed
      PowerPoint slides containing diagrams with incomplete labeling/flowcharts with
      missing steps) pertaining to the DSL topic 1 wk before the scheduled small-group
      DSL presentations. During DSL presentation sessions, which were facilitated by
      teachers, a few students individually presented learning objectives in the
      specified topic. Apart from that, students discussed answers for the questions in
      the prereading assignment. Students were also given an opportunity to use
      technology to support DSL, by way of involving them in Pecha Kucha (PK) talks.
      The impact of the modified DSL method was determined by requesting students to
      respond to a validated questionnaire. Frequency analysis of the responses
      revealed that >60% of students were positive about the modified DSL sessions
      improving their DSL, presentation, collaborative learning, and information
      retrieving skills. Students agreed that PK talks helped them to learn how to
      organize content (65%), present concise information (65.8%), and apply creativity
      (72.5%). Even though small in number, there were comments that the prereading
      assignments were useful for learning. The present study revealed that, even
      though students actively participated in modified DSL sessions, their perceptions
      on satisfaction and usefulness of the same toward achievement of various skills
      were not encouraging. The study generated significant results, which implies that
      undergraduate medical students should be oriented on the relevance of active
      learning strategies in their future studies.

PMID- 29341810
TI  - Beyond "formative": assessments to enrich student learning.
AB  - Formative assessments can enhance and enrich student learning. Typically, these
      have been used to provide feedback against end-of-course standards and prepare
      students for summative assessments of performance or measurement of competence.
      Here, we present the case for using assessments for learning to encompass a wider
      range of important outcomes. We discuss 1) the rationale for using assessment for
      learning; 2) guiding theories of expertise that inform assessment for learning;
      3) theoretical and empirical evidence; 4) approaches to rigor and validation; and
      5) approaches to implementation at multiple levels of the curriculum. The
      literature strongly supports the use of assessments as an opportunity to
      reinforce and enhance learning. Physiology teachers have a wide range of
      theories, models, and interventions from which to prepare students for retention,
      application, transfer, and future learning by using assessments.

PMID- 29341811
TI  - Impact of distance education via interactive videoconferencing on students'
      course performance and satisfaction.
AB  - The impact of distance education via interactive videoconferencing on pharmacy
      students' performance in a course was assessed after implementation of a distance
      campus. Students filled out a "Student Demographic Survey" and a "Precourse
      Knowledge Assessment" at the start of the course and a "Postcourse Knowledge
      Assessment" and a "Postcourse Student Perceptions Survey" at the end of the
      course. The primary end point, a comparison of course grades (%) between the main
      and distance campuses, was examined using the two-sample t-test. We examined the
      relationships among demographics, campus location, course grades, grade point
      average, pre- and postcourse knowledge assessments, and postcourse perceptions as
      our secondary end points with parametric and nonparametric tests. Data from 93
      students were included in the analysis [main campus ( n = 81); distance campus (
      n = 12)]. Students on the main campus achieved a significantly higher final
      course grade (87 vs. 81%; P = 0.02). Scores on the Postcourse Knowledge
      Assessment were also significantly higher compared with those of students on the
      distance education campus (77 vs. 68%; P = 0.04). Students on both campuses
      reported self-perceived improvement in their knowledge base regarding various
      aspects of infectious diseases. Compared with the students on the distance
      campus, those on the main campus were more likely to subjectively perceive that
      they had succeeded in the course ( P = 0.04). Our study suggests that students on
      the main campus achieved a higher final course grade and were more likely to feel
      that they had succeeded in the course. Students on both campuses reported
      improvement in knowledge.

PMID- 29341812
TI  - Optional anatomy and physiology e-learning resources: student access, learning
      approaches, and academic outcomes.
AB  - Anatomy and physiology interactive video clips were introduced into a blended
      learning environment, as an optional resource, and were accessed by ~50% of the
      cohort. Student feedback indicated that clips were engaging, assisted
      understanding of course content, and provided lecture support. Students could
      also access two other optional online resources, lecture capture recordings and
      an interactive atlas of anatomy, and individuals were tracked with respect to
      their access behavior, learning approach, and subject score. Deep learning was
      highest among those accessing the clips or atlas or those accessing more online
      resources, and thus self-regulatory skill development might be a useful approach
      to increase student access to optional online resources. Those who accessed
      clips, lecture capture recordings, or atlas achieved a significantly higher
      subject score than those who did not. When combinations of resources used were
      considered, we found an approximately linear relationship between number of
      resources accessed and subject score, with a 16% difference in score between
      those who accessed none or all of the resources. However, the low resource access
      rate suggests that academic advantage may not be simply due to the learning
      support offered by the resources. As students accessing the optional resources
      tended to be more self-regulated, it may be that it was the extra effort made
      with respect to other subject resources, rather than just the access to the
      online resources, that contributed to higher subject score. Further studies are
      required to establish the relationships between academic performance, optional
      online resource access, and deep learning.

PMID- 29341813
TI  - Regenerative medicine: a vehicle to infuse laboratory-bench modules into an
      exercise physiology curriculum.
AB  - Regenerative medicine is a novel discipline that both excites undergraduates and
      may be used as a vehicle to expose students to scientific concepts and
      opportunities. The goal of this article is to describe the implementation of a
      National Science Foundation-funded Targeted Infusion Project in which
      underrepresented minority undergraduates are exposed to laboratory-bench skills
      and summer research opportunities that they may not have encountered otherwise. A
      3-wk infusion of laboratory-bench and data presentation skills, in the context of
      a regenerative medicine/bioengineering project, aimed to engage students and
      expose them to opportunities as summer researchers and teaching assistants. The
      infusion aimed to assess the extent to which students improved 1) attitudes
      toward laboratory-bench-based techniques, using attitudes toward science as a
      proxy; 2) perceptions of scientific inquiry; 3) intentions to engage in
      undergraduate research; and 4) intentions to persist in science, technology,
      engineering, and mathematics (STEM)-related fields. Results indicate that the 3
      wk infusion had no effect on science attitudes, but transcribed responses to
      structured interviews administered after the summer research experience indicated
      that students who completed summer research projects had positive experiences.
      Differences in intentions to engage in research were detected between groups of
      students in different STEM majors, in addition to differences in intentions to
      pursue a career in science. We describe the implementation of the infusion and
      briefly discuss quantitative outcomes. We conclude that infusion of laboratory
      bench modules in the context of a regenerative medicine/bioengineering project
      may play a small but important role in increasing (minority) participation and
      persistence in the STEM pipeline.

PMID- 29341814
TI  - Utilizing a rat delayed implantation model to teach integrative endocrinology and
      reproductive biology.
AB  - In this teaching laboratory, the students are directed in an exercise that
      involves designing and performing an experiment to determine estrogen's role in
      regulating delayed implantation (diapause) in female rats. To encourage active
      participation by the students, a discussion question is provided before the
      laboratory exercise in which each student is asked to search the literature and
      provide written answers to questions and to formulate an experiment to test the
      role of ovarian estrogen in inducing implantation in female rats. One week before
      the laboratory exercise, students discuss their answers to the questions with the
      instructor to develop an experiment to test their hypothesis that estrogen is
      involved with inducing implantation in the rat. A rat delayed implantation model
      was established that utilizes an estrogen receptor antagonist (ICI 182,780),
      which inhibits the action of ovarian estrogens. Groups of mated females are
      treated with either carrier (control) or ICI 182,780 (ICI) every other day,
      starting on day 2 postcoitus (pc) until day 8 pc. One-half of the females
      receiving ICI are injected with estradiol-17beta on day 8 pc to induce
      implantation 4 days after the controls. If the ICI-treated females are not
      administered estradiol, embryo implantation occurs spontaneously ~4 days after
      the last ICI injection on day 8. This is a very simple protocol that is very
      effective and provides an excellent experiment for student discussion on hormone
      action and the use of agonists and antagonists.

PMID- 29341815
TI  - Development and validation of simulated virtual patients to impart early clinical
      exposure in endocrine physiology.
AB  - In the country presently, preclinical medical students are not routinely exposed
      to real patients. Thus, when they start clinical postings, they are found to have
      poor clinical reasoning skills. Simulated virtual patients (SVPs) can improve
      clinical skills without endangering real patients. This pilot study describes the
      development of two SVPs in endocrine physiology and their validation in terms of
      acquisition of clinical knowledge and student engagement. Two SVPs, Nandini
      Sharma (unintentional weight gain) and Sunil Yadav (polyuria), were created and
      published on the i-Human Patients platform through an iterative,
      interdisciplinary, and transdisciplinary collaborative process using the
      conceptual framework of Kim et al. (Kim S, Phillips WR, Pinsky L, Brock D,
      Phillips K, Keary J. Med Educ 40: 867-876, 2006). After internal and external
      peer validation, the SVPs were piloted on 40 students (20 students per virtual
      patient) over 2 wk. A cognitive pretest was conducted before exposure, and a
      posttest soon after. Faculty and student feedback were collected. Faculty found
      SVPs authentic, helpful as teaching-learning tools, and useful for giving
      feedback and for assessment. Students found SVPs more engaging than paper cases
      and helpful in developing clinical reasoning and in imparting clinical exposure.
      Pretest and posttest scores indicated knowledge gain ( P < 0.01). Although
      challenging to create, SVPs created on the i-Human Patients platform improved
      learning in endocrine physiology and were well accepted by students and faculty
      as a means to provide early clinical exposure. More SVPs can be developed through
      collaboration between stakeholder departments and integrated into the curriculum
      for greater benefit.

PMID- 29341816
TI  - Red cell indexes made easy using an interactive animation: do students and their
      scores concur?
AB  - A good understanding of red cell indexes can aid medical students in a
      considerable manner, serving as a basis to unravel both concepts in red cell
      physiology and abnormalities associated with the same. In this study, we tried to
      assess whether an interactive animation was helpful in improving student
      comprehension and understanding of red cell indexes compared with conventional
      classroom teaching. Eighty-eight first-year MBBS students participated, of which
      44 were assigned to group A and 44 were assigned to group B after randomization.
      After further creation of smaller groups, students were provided with 45 min to
      revise red cell indexes, after which they were required to complete a multimodal
      questionnaire. Group A subgroups used written material for revision, whereas
      group B subgroups had access to an interactive animation. After completion of the
      questionnaire, group A students also used the animation after which feedback was
      collected from all students. Efficacy of the animation to improve learning and
      retention was demonstrated, as group B students scored significantly higher than
      group A students on the questionnaire ( P = 0.0003). A clear majority of the
      students agreed/strongly agreed that the animation was easy to operate, conveyed
      important concepts efficiently, and improved their knowledge of related clinical
      aspects as well. From the results and feedback, we found that the animation was a
      simple, well-received model, which, by significantly improving student
      performance, corroborated our hypothesis that inclusion of interactive animation
      into student curriculum can advance their academic attainment, compared with
      didactic teaching alone.

PMID- 29341817
TI  - Setting national guidelines for physiology undergraduate degree programs.

PMID- 29341818
TI  - Medicine as It Should Be: Teaching Team and Teamwork during a Palliative Care
      Clerkship.
AB  - BACKGROUND: Interprofessional Education (IPE) is an important component of
      medical education. Rotations with palliative care interdisciplinary teams (IDTs)
      provide an optimal environment for IPE and teaching teamwork skills. OBJECTIVE:
      Our objective was to assess the learning of senior medical students during a
      palliative care rotation. DESIGN: A constant comparison method based on grounded
      theory was used in this qualitative study. SETTING/SUBJECTS: Senior medical
      students completed a semi-structured reflective writing exercise after a required
      one-week palliative care clerkship. Sixty randomly selected reflective writings
      were analyzed. MEASUREMENTS: The reflective writings were analyzed to evaluate
      the student's experiences. RESULTS: Dominant themes identified were related to
      teams and teamwork. Eight specific themes were identified: value of IDT for team
      members; value of IDT for patient/family; importance of each team member;
      reliance on other team members; roles of team members; how teams work; team
      communication; and interdisciplinary assessment and care planning. Students
      described exposure to novel experiences and planned to incorporate newly learned
      behaviors in their future practice. CONCLUSION: By participating in palliative
      care IDTs, medical students consistently learned about teamwork within
      healthcare. Additionally, they learned the importance of such teamwork to
      patients and the team itself. Rotations with palliative care IDTs have a
      significant role to play in IPE and preparing medical students to practice on
      teams.

PMID- 29341819
TI  - From the desk of Peter F. Buckley, MD.

PMID- 29341820
TI  - Comments on Abilify MyCite.

PMID- 29341821
TI  - Deuterium Tetrabenazine for Tardive Dyskinesia.
AB  - Tardive dyskinesia remains a significant, potentially stigmatizing or crippling
      adverse effect for any patient treated with an antipsychotic medication. While
      second- and third-generation antipsychotics have exhibited lower annual incidence
      rates for tardive dyskinesia than classic or first-generation agents, 3.9% versus
      5.5%, the estimated incidence rate is only modestly lower. When coupled with the
      fact that second- and third-generation antipsychotic medications have come to be
      employed in treating a wider range of disorders (e.g., autism spectrum disorders,
      mood disorders, personality disorders, etc.), it is clear that the population of
      patients exposed to the risk of tardive dyskinesia has expanded. On April 3,
      2017, the U.S. Food and Drug Administration (FDA) approved a deuterated version
      of tetrabenazine (Xenozine(r)) for the treatment of the involuntary choreic
      movements associated with Huntington's disease. More recent data, however, have
      indicated that deuterium tetrabenazine or deutetrabenazine (Austedo(r)) is
      effective in treating tardive dyskinesia. Moreover, like the other derivative of
      tetrabenazine, valbenazine (Ingrezza(r)), deutetrabenazine offers less frequent
      dosing and a better short-term adverse effect profile than that of tetrabenazine.
      Longer use in a broader range of patients, however, will be required to identify
      risks and benefits not found in short-term trials, as well as optimal use
      parameters for treatment of tardive dyskinesia.

PMID- 29341822
TI  - Aripiprazole Long-Acting Injectable for Maintenance Treatment of Bipolar I
      Disorder in Adults.
AB  - Bipolar I disorder is a serious and disabling psychiatric illness. It is
      associated with a significant reduction in quality of life and an increased risk
      for suicide. Pharmacotherapy is essential for both the acute and maintenance
      treatment of bi-polar I disorder. While multiple oral medications are recommended
      for the maintenance treatment, there are not many long-acting injectable
      medications approved for this indication. New treatments that would improve
      patient adherence have the potential for decreasing relapses and improving
      patients' ability to remain functional members of society. In this paper we
      discuss the available data for safety and efficacy of aripiprazole long-acting
      injectable in bipolar disorder.

PMID- 29341823
TI  - Clinical News.

PMID- 29341824
TI  - Intestinal lymph as a readout of meal-induced GLP-1 release in an unrestrained
      rat model.
AB  - Intestinal lymph supposedly provides a readout for the secretion of intestinal
      peptides. We here assessed how mesenteric lymph duct (MLD) lymph levels of
      glucagon-like peptide (GLP-1), insulin, and metabolites [glucose and
      triglycerides (TG)] evolve after isocaloric high- and low-fat diet (HFD and LFD)
      meals and how they compare with hepatic portal vein (HPV) plasma levels.
      Moreover, we examined the effects of intraperitoneally administered GLP-1 (1 or
      10 nmol/kg) on these parameters. At 20 min after the HFD meal onset, GLP-1 levels
      were higher in MLD lymph than in HPV plasma. No such difference occurred with the
      LFD meal. Intraperitoneal injections of 10 nmol/kg GLP-1 before meals enhanced
      the meal-induced increases in MLD lymph and HPV plasma GLP-1 levels except for
      the MLD lymph levels after the HFD meal. Intraperitoneal injection of 1 nmol/kg
      GLP-1 only increased HPV plasma GLP-1 levels at 60 min after the HFD meal. GLP-1
      injections did not increase the MLD lymph or HPV plasma GLP-1 concentrations
      beyond the physiological range, suggesting that intraperitoneal GLP-1 injections
      can recapitulate the short-term effects of endogenous GLP-1. Dipeptidyl peptidase
      IV (DPP-IV) activity in MLD lymph was lower than in HPV plasma, which presumably
      contributed to the higher levels of GLP-1 in lymph than in plasma. Insulin and
      glucose showed similar profiles in MLD lymph and HPV plasma, whereas TG levels
      were higher in lymph than in plasma. These results indicate that intestinal lymph
      provides a sensitive readout of intestinal peptide release and potential action,
      in particular when fat-rich diets are consumed.

PMID- 29341825
TI  - A predictive model of rat calorie intake as a function of diet energy density.
AB  - Easy access to high-energy food has been linked to high rates of obesity in the
      world. Understanding the way that access to palatable (high fat or high calorie)
      food can lead to overconsumption is essential for both preventing and treating
      obesity. Although the body of studies focused on the effects of high-energy diets
      is growing, our understanding of how different factors contribute to food choices
      is not complete. In this study, we present a mathematical model that can predict
      rat calorie intake to a high-energy diet based on their ingestive behavior to a
      standard chow diet. Specifically, we propose an equation that describes the
      relation between the body weight ( W), energy density ( E), time elapsed from the
      start of diet ( T), and daily calorie intake ( C). We tested our model on two
      independent data sets. Our results show that the suggested model can predict the
      calorie intake patterns with high accuracy. Additionally, the only free parameter
      of our proposed equation (rho), which is unique to each animal, has a strong
      correlation with their calorie intake.

PMID- 29341827
TI  - Multitasking: a challenge for the kidney.

PMID- 29341826
TI  - u-Opioid receptors inhibit the exercise pressor reflex by closing N-type calcium
      channels but not by opening GIRK channels in rats.
AB  - u-Opioid G protein-coupled receptors (MOR) interact with ion channels to decrease
      neuronal excitability. In humans, intrathecal administration of the MOR agonist
      fentanyl inhibits the exercise pressor reflex, an effect that can be attributed
      to either the opening of inward rectifying potassium channels (GIRK) or the
      closing of N-type calcium channels. The purpose of this study was to determine if
      the highly selective MOR agonist [d-Ala2, N-MePhe4,Gly-ol]-enkephalin (DAMGO)
      attenuates the exercise pressor reflex and which of these two channels are
      responsible for this effect. In decerebrate rats, we determined the effect of
      intrathecal injection of either tertiapin-LQ, which blocks the GIRK channel or
      omega-conotoxin-GVIA, which blocks the N-type calcium channel on the exercise
      pressor reflex, which was evoked by contracting the triceps surae muscles.
      Initially, we established that intrathecal injection of DAMGO inhibited the
      exercise pressor reflex relative to no intrathecal injection or intrathecal
      saline injection ( P < 0.001, n = 5). We then found that intrathecal injection of
      two doses of tertiapin-LQ (1 and 10 ug) had no effect on the exercise pressor
      reflex ( n = 6 and n = 7, respectively; P > 0.05). Importantly, neither dose of
      tertiapin-LQ prevented the DAMGO-induced inhibition of the exercise pressor
      reflex. Last, we found that intrathecal injection of omega-conotoxin-GVIA
      markedly attenuated the exercise pressor reflex ( P < 0.001, n = 7). The
      cardioaccelerator response to contraction did not appear to be effected in any of
      the experiments. We conclude that N-type voltage-gated calcium channel inhibition
      appears to be the mechanism by which MOR activation inhibits the exercise pressor
      reflex in decerebrate rats.

PMID- 29341828
TI  - Biosensors for spatiotemporal detection of reactive oxygen species in cells and
      tissues.
AB  - Redox biology has become a major issue in numerous areas of physiology. Reactive
      oxygen species (ROS) have a broad range of roles from signal transduction to
      growth control and cell death. To understand the nature of these roles, accurate
      measurement of the reactive compounds is required. An increasing number of tools
      for ROS detection is available; however, the specificity and sensitivity of these
      tools are often insufficient. Furthermore, their specificity has been rarely
      evaluated in complex physiological conditions. Many ROS probes are sensitive to
      environmental conditions in particular pH, which may interfere with ROS detection
      and cause misleading results. Accurate detection of ROS in physiology and
      pathophysiology faces additional challenges concerning the precise localization
      of the ROS and the timing of their production and disappearance. Certain ROS are
      membrane permeable, and certain ROS probes move across cells and organelles.
      Targetable ROS probes such as fluorescent protein-based biosensors are required
      for accurate localization. Here we analyze these challenges in more detail,
      provide indications on the strength and weakness of current tools for ROS
      detection, and point out developments that will provide improved ROS detection
      methods in the future. There is no universal method that fits all situations in
      physiology and cell biology. A detailed knowledge of the ROS probes is required
      to choose the appropriate method for a given biological problem. The knowledge of
      the shortcomings of these probes should also guide the development of new
      sensors.

PMID- 29341829
TI  - Climatic modulation of neurotransmitter release in amphibian neuromuscular
      junctions: role of dynorphin-A.
AB  - Amphibian neuromuscular junctions (NMJs) become relatively more silent during the
      dry winter season in Australia. During the dry, calcium sensitivity is reduced,
      whereas calcium dependence remains unchanged. Endogenous opioid peptides play an
      important role in the regulation of the physiological functions of active and
      dormant vertebrates. Previous findings suggest that dynorphin-A is more potent
      than other opiates in decreasing evoked neurotransmission in amphibian NMJs.
      Dynorphin-A has been shown not to alter the amplitude or the frequency of
      miniature quantal neurotransmitter release. In the present study, we report that
      dynorphin-A exerted a more pronounced inhibitory effect on evoked
      neurotransmitter release during the dry (hibernating period) when compared with
      the wet (active period) season. Dynorphin-A increased the frequency and decreased
      the amplitude of miniature neurotransmitter release only at relatively high
      concentration during the dry season. In the present study, we propose that
      dynorphin-A suppresses evoked neurotransmitter release and thus contraction of
      skeletal muscles, while allowing subthreshold activation of the NMJ by miniature
      neurotransmission, thus preventing any significant neuromuscular remodeling. The
      inhibitory effect of dynorphin-A on evoked transmitter release is reduced by
      increasing the extracellular calcium concentration.

PMID- 29341830
TI  - Pregnancy-related hormones, progesterone and human chorionic gonadotrophin,
      upregulate expression of maternal plasma gelsolin.
AB  - Plasma gelsolin (pGSN), a protein primarily involved in clearance of circulating
      actin filaments, is an upcoming novel biomarker. Its level changes in multiple
      disease and injury conditions, attributable mainly to its consumption during
      actin clearance; the endogenous regulation of its expression, however, remains
      elusive as well as unexplored. Here, we are reporting the first isolation of the
      promoter region of pGSN gene and investigation of its transcriptional regulation
      during pregnancy (a natural process associated with a well-programmed injury
      course of parturition). Interestingly, two of the pregnancy-related hormones,
      human chorionic gonadotrophin (hCG) and progesterone, significantly upregulated
      pGSN promoter activity in muscle cells. This action of both hormones was found to
      mediate through their respective cellular receptors and involved a contribution
      of multiple signaling pathways including those of protein kinase A, protein
      kinase C, epidermal growth factor receptor and prostaglandin-endoperoxidase
      synthase 2 in the case of hCG-mediated upregulation. This novel upregulation was
      further supported by elevated levels of endogenous pGSN transcripts as well as
      secreted protein upon hormonal treatments of muscle cells compared with untreated
      controls. A participation of pGSN promoter cis-elements, capable of interacting
      with endogenous transcription factors, Ap1, Sp1, and p300, was also observed
      during this hormonal upregulation. Additionally, the augmented pGSN levels
      observed in pregnant mice compared with the control animals further supported an
      upregulation of this protein during pregnancy, implicating vital role(s) played
      by pGSN during this period in mammals.

PMID- 29341831
TI  - Role of Bone-Modifying Agents in Multiple Myeloma: American Society of Clinical
      Oncology Clinical Practice Guideline Update.
AB  - Purpose To update guideline recommendations on the role of bone-modifying agents
      in multiple myeloma. Methods An update panel conducted a targeted systematic
      literature review by searching PubMed and the Cochrane Library for randomized
      controlled trials, systematic reviews, meta-analyses, clinical practice
      guidelines, and observational studies. Results Thirty-five relevant studies were
      identified, and updated evidence supports the current recommendations.
      Recommendations For patients with active symptomatic multiple myeloma that
      requires systemic therapy with or without evidence of lytic destruction of bone
      or compression fracture of the spine from osteopenia on plain radiograph(s) or
      other imaging studies, intravenous administration of pamidronate 90 mg over at
      least 2 hours or zoledronic acid 4 mg over at least 15 minutes every 3 to 4 weeks
      is recommended. Denosumab has shown to be noninferior to zoledronic acid for the
      prevention of skeletal-related events and provides an alternative. Fewer adverse
      events related to renal toxicity have been noted with denosumab compared with
      zoledronic acid and may be preferred in this setting. The update panel recommends
      that clinicians consider reducing the initial pamidronate dose in patients with
      preexisting renal impairment. Zoledronic acid has not been studied in patients
      with severe renal impairment and is not recommended in this setting. The update
      panel suggests that bone-modifying treatment continue for up to 2 years. Less
      frequent dosing has been evaluated and should be considered in patients with
      responsive or stable disease. Continuous use is at the discretion of the treating
      physician and the risk of ongoing skeletal morbidity. Retreatment should be
      initiated at the time of disease relapse. The update panel discusses measures
      regarding osteonecrosis of the jaw. Additional information is available at
      www.asco.org/hematologic-malignancies-guidelines and www.asco.org/guidelineswiki
      .

PMID- 29341832
TI  - Racial Differences in 21-Gene Recurrence Scores Among Patients With Hormone
      Receptor-Positive, Node-Negative Breast Cancer.
AB  - Purpose The 21-gene recurrence score (RS) breast cancer assay is clinically used
      to quantify risk of 10-year distant recurrence by category (low, < 18;
      intermediate, 18 to 30; high, >= 31) for treatment management among women
      diagnosed with hormone receptor-positive, human epidermal growth factor receptor
      2-negative, lymph node-negative breast cancer. Although non-Hispanic black (NHB)
      women have worse prognosis compared with non-Hispanic white (NHW) women, the
      equivalency of 21-gene RS across racial groups remains unknown. Patients and
      Methods Using the Metropolitan Detroit Cancer Surveillance System, we identified
      women who were diagnosed with hormone receptor-positive, human epidermal growth
      factor receptor 2-negative, lymph node-negative invasive breast cancer between
      2010 and 2014. Multinomial logistic regression was used to quantify racial
      differences in 21-gene RS category. Results We identified 2,216 women (1,824 NHW
      and 392 NHB) with invasive breast cancer who met clinical guidelines for and
      underwent 21-gene RS testing. The mean RS was significantly higher in NHBs
      compared with NHWs (19.3 v 17.0, respectively; P = .0003), where NHBs were more
      likely to present with high-risk tumors compared with NHWs (14.8% v 8.3%,
      respectively; P = .0004). These differences were limited to patients younger than
      65 years at diagnosis, among whom NHBs had significantly higher RS compared with
      NHWs (20 to 49 years: 23.6 v 17.3, respectively; P < .001 and 50 to 64 years:
      19.6 v 17.4, respectively; P = .023). NHBs remained more likely to have high-risk
      tumors compared with NHWs after adjusting for age, clinical stage, tumor grade,
      and histology (odds ratio [OR], 1.75; 95% CI, 1.18 to 2.59). Conclusion NHBs who
      met clinical criteria for 21-gene RS testing had tumors with higher estimated
      risks of distant recurrence compared with NHWs. Further study is needed to
      elucidate whether differences in recurrence are observed for these women, which
      would have clinical implications for 21-gene RS calibration and treatment
      recommendations in NHB patients.

PMID- 29341833
TI  - Immune-Modified Response Evaluation Criteria In Solid Tumors (imRECIST): Refining
      Guidelines to Assess the Clinical Benefit of Cancer Immunotherapy.
AB  - Purpose Treating solid tumors with cancer immunotherapy (CIT) can result in
      unconventional responses and overall survival (OS) benefits that are not
      adequately captured by Response Evaluation Criteria In Solid Tumors (RECIST)
      v1.1. We describe immune-modified RECIST (imRECIST) criteria, designed to better
      capture CIT responses. Patients and Methods Atezolizumab data from clinical
      trials in non-small-cell lung cancer, metastatic urothelial carcinoma, renal cell
      carcinoma, and melanoma were evaluated. Modifications to imRECIST versus RECIST
      v1.1 included allowance for best overall response after progressive disease (PD)
      and changes in PD definitions per new lesions (NLs) and nontarget lesions.
      imRECIST progression-free survival (PFS) did not count initial PD as an event if
      the subsequent scan showed disease control. OS was evaluated using conditional
      landmarks in patients whose PFS differed by imRECIST versus RECIST v1.1. Results
      The best overall response was 1% to 2% greater, the disease control rate was 8%
      to 13% greater, and the median PFS was 0.5 to 1.5 months longer per imRECIST
      versus RECIST v1.1. Extension of imRECIST PFS versus RECIST v1.1 PFS was
      associated with longer or similar OS. Patterns of progression analysis revealed
      that patients who developed NLs without target lesion (TL) progression had a
      similar or shorter OS compared with patients with RECIST v1.1 TL progression.
      Patients infrequently experienced a spike pattern (TLs increase, then decrease)
      but had longer OS than patients without TL reversion. Conclusion Evaluation of
      PFS and patterns of response and progression revealed that allowance for TL
      reversion from PD per imRECIST may better identify patients with OS benefit.
      Progression defined by the isolated appearance of NLs, however, is not associated
      with longer OS. These results may inform additional modifications to radiographic
      criteria (including imRECIST) to better reflect efficacy with CIT agents.

PMID- 29341834
TI  - Improvement in Overall Survival With Carfilzomib, Lenalidomide, and Dexamethasone
      in Patients With Relapsed or Refractory Multiple Myeloma.
AB  - Purpose In the ASPIRE study of carfilzomib, lenalidomide, and dexamethasone (KRd)
      versus lenalidomide plus dexamethasone (Rd) in patients with relapsed or
      refractory multiple myeloma, progression-free survival was significantly improved
      in the carfilzomib group (hazard ratio, 0.69; two-sided P < .001). This
      prespecified analysis reports final overall survival (OS) data and updated safety
      results. Patients and Methods Adults with relapsed multiple myeloma (one to three
      prior lines of therapy) were eligible and randomly assigned at a one-to-one ratio
      to receive KRd or Rd in 28-day cycles until withdrawal of consent, disease
      progression, or occurrence of unacceptable toxicity. After 18 cycles, all
      patients received Rd only. Progression-free survival was the primary end point;
      OS was a key secondary end point. OS was compared between treatment arms using a
      stratified log-rank test. Results Median OS was 48.3 months (95% CI, 42.4 to 52.8
      months) for KRd versus 40.4 months (95% CI, 33.6 to 44.4 months) for Rd (hazard
      ratio, 0.79; 95% CI, 0.67 to 0.95; one-sided P = .0045). In patients receiving
      one prior line of therapy, median OS was 11.4 months longer for KRd versus Rd; it
      was 6.5 months longer for KRd versus Rd among patients receiving >= two prior
      lines of therapy. Rates of treatment discontinuation because of adverse events
      (AEs) were 19.9% (KRd) and 21.5% (Rd). Grade >= 3 AE rates were 87.0% (KRd) and
      83.3% (Rd). Selected grade >= 3 AEs of interest (grouped terms; KRd v Rd)
      included acute renal failure (3.8% v 3.3%), cardiac failure (4.3% v 2.1%),
      ischemic heart disease (3.8% v 2.3%), hypertension (6.4% v 2.3%), hematopoietic
      thrombocytopenia (20.2% v 14.9%), and peripheral neuropathy (2.8% v 3.1%).
      Conclusion KRd demonstrated a statistically significant and clinically meaningful
      reduction in the risk of death versus Rd, improving survival by 7.9 months. The
      KRd efficacy advantage is most pronounced at first relapse.

PMID- 29341835
TI  - Increasing Our Understanding of an Overlooked Public Health Epidemic: Traumatic
      Brain Injuries in Women Subjected to Intimate Partner Violence.

PMID- 29341836
TI  - A Cohort Study of Patient-Reported Outcomes and Healthcare Utilization in Acute
      Myeloid Leukemia Patients Receiving Active Cancer Therapy in the Last Six Months
      of Life.
AB  - BACKGROUND: Evidence about the unique palliative care needs of patients with
      acute myeloid leukemia (AML) is limited. Improving the care of these patients
      will require a better understanding of their unmet needs, including symptom
      burden at the end of life, and patterns of healthcare utilization. OBJECTIVE: To
      describe AML patients' experiences in the last six months of life regarding
      symptom burden, blood product utilization, and use of palliative care services.
      METHODS: Exploratory analysis of prospectively collected patient-reported
      outcomes and healthcare utilization data during the last six months of life among
      33 AML patients who died during a longitudinal observational study. RESULTS:
      Symptom burden, quality of life (QOL), and psychological distress worsened with
      proximity to death. Of the 26 patients with utilization data, most (n = 24;
      92.4%) were hospitalized in the last month of life, with 26.9% (n = 7) dying in
      the intensive care unit. Patients required a median of 16 red blood cell
      transfusions in the last six months of life, and those with a high transfusion
      burden in the last month of life had a higher rate of in-hospital death (blood
      transfusions: p < 0.01; platelet transfusions: p = 0.03). Only six patients
      enrolled in hospice (23.1%). DISCUSSION: Patients with AML have marked symptoms
      and QOL impairments that escalate in the final six months of life. Patients
      entering the healthcare system for active cancer treatment are likely to continue
      disease-oriented care until death. High rates of hospitalization and blood
      product transfusion are a direct barrier to transitioning to hospice care.

PMID- 29341837
TI  - Ocular Permeation of Topical Tazocin and Its Effectiveness in the Treatment of
      Pseudomonas aeruginosa Induced Keratitis in Rabbits.
AB  - PURPOSE: Pseudomonas aeruginosa is the most common causative organism for contact
      lens-associated corneal ulcer and is commonly treated with fluoroquinolones. With
      the emergence of resistant strains, it is important to investigate alternative
      therapies. Despite well-established efficacy of tazocin against systemic
      Pseudomonas infections, its topical use for the treatment of Pseudomonas
      keratitis has not been described, hence this study was aimed to find the ocular
      permeation of Tazocin and its efficacy in treating keratitis in rabbit eyes.
      METHODS: We investigated the ocular permeation of topical tazocin after single
      drop application in normal rabbit eyes by estimating piperacillin and tazobactam
      concentrations in cornea, aqueous, and vitreous using a validated LC-MS/MS
      method. Furthermore, we determined the efficacy of repeated dose administration
      of tazocin against experimentally induced P. aeruginosa keratitis in rabbits in
      comparison to moxifloxacin. To determine the efficacy, clinical examination,
      histopathological examination, and estimation of bacterial load and inflammatory
      cytokines in cornea were done. RESULTS: Significant corneal concentration of
      piperacillin and tazobactam was detected in normal rabbit corneas after single
      dose treatment with tazocin. In rabbits with Pseudomonas-induced keratitis,
      topical tazocin caused significant clinical and histopathological improvement.
      This improvement was associated with reduction in corneal bacterial load and
      inflammatory cytokines. Compared to moxifloxacin 0.5%, tazocin treated group
      showed greater clinical response which was associated with higher interleukin
      (IL)-1beta, lower tumor necrosis factor (TNF)-alpha, a comparable level of IL-8,
      greater reduction in corneal bacterial load, and lesser inflammatory cell
      infiltration. CONCLUSION: Tazocin showed good ocular penetration and was
      effective in treatment of Pseudomonas induced keratitis in rabbits.

PMID- 29341838
TI  - Immobilization of cross-linked tannase enzyme on multiwalled carbon nanotubes and
      its catalytic behavior.
AB  - Immobilization of cross-linked tannase on pristine multiwalled carbon nanotubes
      (MWCNT) was successfully performed. Cross-linking of tannase molecules was made
      through glutaraldehyde. The immobilized tannase exhibited significantly improved
      pH, thermal, and recycling stability. The optimal pH for both free and
      immobilized tannase was observed at pH 5.0 with optimal operating temperature at
      30 degrees C. Moreover, immobilized enzyme retained greater biocatalytic
      activities upon 10 repeated uses compared to free enzyme in solution.
      Immobilization of tannase was accomplished by strong hydrophobic interaction most
      likely between hydrophobic amino acid moieties of the glutaraldehyde-cross-linked
      tannase to the MWCNT.

PMID- 29341839
TI  - Activation of Frataxin Protein Expression by Antisense Oligonucleotides Targeting
      the Mutant Expanded Repeat.
AB  - Friedreich's Ataxia (FA) is an inherited neurologic disorder caused by an
      expanded GAA repeat within intron 1 of the frataxin (FXN) gene that reduces
      expression of FXN protein. Agents that increase expression of FXN have the
      potential to alleviate the disease. We previously reported that duplex RNAs
      (dsRNAs) and antisense oligonucleotides (ASOs) complementary to the GAA repeat
      could enhance expression of FXN protein. We now explore the potential of a
      diverse group of chemically modified dsRNAs and ASOs to define the breadth of
      repeat-targeted synthetic nucleic acids as a platform for therapeutic development
      for FA. ASOs and dsRNAs can activate FXN protein expression in FA patient-derived
      cell lines that possess varied numbers of GAA repeats. Increased FXN protein
      expression was achieved by ASOs incorporating diverse chemical modifications with
      low nanomolar potencies, suggesting substantial flexibility in choosing compounds
      for further chemical optimization and animal studies. Our data encourage further
      development of ASOs as agents to treat FA.

PMID- 29341840
TI  - Surgical Site Infections after Open Reduction Internal Fixation for Trauma in Low
      and Middle Human Development Index Countries: A Systematic Review.
AB  - BACKGROUND: Musculoskeletal trauma represents a large source of morbidity in low
      and middle human development index countries (LMHDICs). Open reduction and
      internal fixation (ORIF) of traumatic long bone fractures definitively manages
      these injuries and restores function when conducted safely and effectively.
      Surgical site infections (SSIs) are a common complication of operative fracture
      fixation, although the risks of infection are ill-defined in LMHDIC. PATIENTS AND
      METHODS: This study reviewed systematically all studies describing SSI after ORIF
      in LMDHICs. Studies were reviewed based on their qualitative characteristics,
      after which a quantitative synthesis of weighted pooled infection rates based on
      available patient-level data was performed to estimate published incidence of
      SSI. RESULTS: Forty-two studies met criteria for qualitative review and 32
      studies comprising 3,084 operations were included in the quantitative analysis.
      Among 3,084 operations, the weighted pooled SSI rate was 6.4 infections per 100
      procedures (95% confidence interval [CI] 4.6-8.2 infections per 100 procedures).
      Higher rates of infection were noted among the sub-group of open fractures (95%
      CI 13.9-23.0 infections per 100 procedures). Lower extremity injuries and
      procedures utilizing intra-medullary nails also had slightly higher rates of
      infection versus upper extremity procedures and other fixation devices.
      CONCLUSIONS: Reported rates of SSI after ORIF are higher in LMHDICs, and may be
      driven by high rates of infection in the sub-group of open fractures. This study
      provides a baseline SSI rate obtained from literature produced from LMHDICs.
      Infection rates are highly dependent on fracture sub-types.

PMID- 29341841
TI  - Redefining Hypertension - Assessing the New Blood-Pressure Guidelines.

PMID- 29341842
TI  - Purification and characterization of fibrinolytic protease from Bacillus
      amyloliquefaciens MCC2606 and analysis of fibrin degradation product by MS/MS.
AB  - A serine protease with preference for fibrin protein was purified and
      characterized from Bacillus amyloliquefaciens MCC2606, isolated from dosa batter.
      The protease was purified using ammonium sulfate precipitation, ion-exchange, and
      gel filtration chromatography. The degradation activity of the protease toward
      the fibrin was significantly higher compared with other protein substrates in the
      study. The molecular weight of the CFR15-protease was estimated to be 32 kDa
      based on SDS-PAGE. The purified enzyme exhibited both fibrinolytic and
      fibrinogenolytic activity. The optimum pH and temperature for the activity of the
      enzyme was found to be 10.5 and 45 degrees C. A significant inhibition was seen
      with the protease inhibitors phenyl methyl sulphonyl fluoride and ethylene
      diamine tetra acetic acid and the activity of the enzyme was enhanced in presence
      of Mn2+. There was an observed increase in vitro activated partial thromboplastin
      time and prothrombin time of both time and dose dependent study. Among the four
      chains of fibrin, the beta-chain of fibrin appears to be the primary component
      and site susceptible for CFR15-protease in early action as indicated by MS/MS
      analysis of initial degradation products. These results indicated that the CFR15
      protease have the potential to be an effective fibrinolytic agent.

PMID- 29341843
TI  - Smart Care Based on Telemonitoring and Telemedicine for Type 2 Diabetes Care:
      Multi-Center Randomized Controlled Trial.
AB  - BACKGROUND: This study was performed to determine the effectiveness of the Smart
      Care service on glucose control based on telemedicine and telemonitoring compared
      with conventional treatment in patients with type 2 diabetes. MATERIALS AND
      METHODS: This 24-week prospective multi-center randomized controlled trial
      involved 338 adult patients with type 2 diabetes at four university hospitals in
      South Korea. The patients were randomly assigned to a control group (group A, n =
      113), a telemonitoring group (group B, n = 113), or a telemedicine group (group
      C, n = 112). Patients in the telemonitoring group visited the outpatient clinic
      regularly, accompanied by an additional telemonitoring service that included
      remote glucose monitoring with automated patient decision support by text. Remote
      glucose monitoring was identical in the telemedicine group, but assessment by
      outpatient visits was replaced by video conferencing with an endocrinologist.
      RESULTS: The adjusted net reductions in HbA1c concentration after 24 weeks were
      similar in the conventional, telemonitoring, and telemedicine groups (-0.66% +/-
      1.03% vs. -0.66% +/- 1.09% vs. -0.81% +/- 1.05%; p > 0.05 for each pairwise
      comparison). Fasting glucose concentrations were lower in the telemonitoring and
      telemedicine groups than in the conventional group. Rates of hypoglycemia were
      lower in the telemedicine group than in the other two groups, and compliance with
      medication was better in the telemonitoring and telemedicine than in the
      conventional group. No serious adverse events were associated with telemedicine.
      CONCLUSIONS: Telehealthcare was as effective as conventional care at improving
      glycemia in patients with type 2 diabetes without serious adverse effects.

PMID- 29341844
TI  - Empiric Antibiotics for Sepsis.
AB  - BACKGROUND: Sepsis is life-threatening organ dysfunction caused by a dysregulated
      host response to infection. Early recognition and treatment are the cornerstones
      of management. METHODS: Review of the English-language literature. RESULTS: For
      both sepsis and septic shock "antimicrobials [should be] be initiated as soon as
      possible and within one hour" (Surviving Sepsis Campaign). The risk of
      progression from severe sepsis to septic shock increases 8% for each hour before
      antibiotics are started. Selection of antimicrobial agents is based on a
      combination of patient factors, predicted infecting organism(s), and local
      microbial resistance patterns. The initial drugs should have activity against
      typical gram-positive and gram-negative causative micro-organisms. Anaerobic
      coverage should be provided for intra-abdominal infections or others where
      anaerobes are significant pathogens. Empiric antifungal or antiviral therapy may
      be warranted. For patients with healthcare-associated infections, resistant micro
      organisms will further complicate the choice of empiric antimicrobials.
      Recommendations are given for specific infections. CONCLUSION: Early
      administration of broad-spectrum antimicrobial drugs is one of the most
      important, if not the most important, treatment for patients with sepsis or
      septic shock. Drugs should be initiated as soon as possible, and the choice of
      should take into account patient factors, common local pathogens, hospital
      antibiograms and resistance patterns, and the suspected source of infection.
      Antimicrobial agent therapy should be de-escalated as soon as possible.

PMID- 29341845
TI  - Outside in - inside out. Creating focus on the patient - a vaccine company
      perspective.
AB  - Involving patients in the development of medicines and vaccines should result in
      benefits to patients. The vaccine recipient is usually a healthy person. We
      describe the rationale and implementation of a vaccine company's initiative to
      encourage employees to identify with patients of the conditions prevented by the
      vaccines they help to produce. The Voice of the Patient ("VoP"), begun in 2014,
      is an educational programme directed at the 16,000 employees of a global vaccine
      company. It engages employees through an understanding that they are all "vaccine
      patients", and that they can make a difference by considering the impact of
      decisions made in their day to day work. The initiative includes presentations
      about vaccine-preventable diseases, global live webcasts with experts and
      patients, employee visits to healthcare facilities in developing countries, and
      the production of patient-focused sections in research publications. In a 2017
      employee survey, 90% of respondents said they know how their daily work impacts
      patients and they demonstrate focus on patients. We believe this is preliminary
      evidence that, by supporting employee awareness of the impact of their individual
      roles, VoP could be a model for a type of initiative that will contribute to
      industry's continuing evolution towards more patient-centred healthcare.

PMID- 29341847
TI  - Interview with Prof. Shannon N. Conley, James Madison University. Why Does Social
      Context of Technology Matter?

PMID- 29341846
TI  - Primary Intra-Medullary Nailing of Open Tibia Fractures Caused by Low-Velocity
      Gunshots: Does Operative Debridement Increase Infection Rates?
AB  - BACKGROUND: Although gunshot-induced extremity fractures are typically not
      considered open fractures, there is controversy regarding wound management in the
      setting of operative fixation to limit infection complications. Previous studies
      have evaluated the need for a formal irrigation and debridement (I&D) prior to
      intra-medullary nailing (IMN) of gunshot-induced femur fractures but none have
      specifically evaluated tibias. By comparing primary IMN for tibial shaft
      fractures caused by low-velocity firearms additionally treated with a formal
      operative I&D (group 1) with those without an I&D (group 2), we sought to
      identify whether there are: differences in treatment group infection rates;
      particular fracture patterns more prone to infection; and patient characteristics
      more prone to infections. PATIENTS AND METHODS: Retrospective cohort study at a
      single level I trauma center of gunshot-induced tibial shaft fractures managed
      primarily with IMN in 39 patients from October 1, 2008 to October 30, 2016. The
      following were studied: demographics, follow-up, fracture characteristics, injury
      management, and patient outcome. Fractures were categorized based on the
      Orthopaedic Trauma Association (OTA) classification system for diaphyseal
      tibia/fibula fractures. All patients had intravenous antibiotic agents at
      presentation and received three days of post-operative intravenous antibiotic
      agents per institutional protocol. RESULTS: In group 1, 6 of 23 patients (26.1%)
      developed superficial infections and 4 of 23 patients (17.4%) developed deep
      infections. In group 2, none of 16 patients (0%) developed superficial infections
      and 1 patient (6.25%) developed a deep infection, making the total cohort
      infection rate 28.2% (11/39). Superficial infections were associated with a
      formal I&D whereas deep infections were not. Tobacco smokers and type 42-A
      fractures had higher infection rates when treated with a formal I&D. CONCLUSION:
      A formal debridement, followed by primary IMN in tibia fractures caused by low
      velocity firearms is associated with an increased risk of superficial infection
      that is well managed with antibiotic agents, but the incorporation of a
      debridement does not affect rate of deep infection. A formal I&D during IMN
      fixation should be avoided in patients that are smokers and have type 42-A tibia
      fractures as these are factors associated with increased infection rates.

PMID- 29341848
TI  - Protection of root apex meristem during stress responses.
AB  - By regulating the levels of nitric oxide (NO) in a cell and tissue specific
      fashion, Phytoglobins (Pgbs), plant hemoglobin-like proteins, interfere with many
      NO-mediated pathways participating in developmental and stress-related responses.
      Recent evidence reveals that one of the functions of Pgbs is to protect the root
      apical meristem (RAM) from stress conditions by retaining the viability and
      function of the quiescent center (QC), required to maintain the stem cells in an
      undifferentiated state and ensure proper tissue patterning and root viability.
      Based on this and other evidence, it is suggested that Pgbs regulate cell fate by
      modulating NO homeostasis.

PMID- 29341849
TI  - Factors affecting occlusion pressure and ischemic preconditioning.
AB  - PURPOSE: To determine the effect of limb selection (upper/lower), cuff width
      (small (6 cm)/medium (13 cm) upper; medium/large (18 cm) lower) and anthropometry
      on arterial occlusion pressure (AOP) in ischemic preconditioning (IPC). METHODS:
      Twenty athletes (10 females and 10 males) had surface anthropometry and dual x
      ray absorptiometry (DXA) assessments before using Doppler ultrasound to confirm
      AOP for each limb. Subsequently, 5 min of occlusion occurred, with near-infrared
      spectroscopy (NIRS) measuring muscle oxygenation changes. Resultant AOP was
      compared between sexes, limbs and cuff sizes using linear regression models.
      RESULTS: Mean AOP was higher in the lower limbs than the upper limbs (161 +/- 18
      vs. 133 +/- 12 mm Hg; p < .001), and with smaller cuffs in upper (161 +/- 16 vs.
      133 +/- 12 mm Hg; p < .001), but not lower limbs (161 +/- 16 vs. 170 +/- 26 mm
      Hg; p = .222). Sex and resting systolic blood pressure (SBP) accounted for 77%
      (small cuff) to 83% (medium cuff) of variance in AOP for upper limbs, and 61%
      (medium cuff) to 63% (large cuff) in lower limbs. Including anthropometry
      accounted for 82% (small cuff) to 89% (medium cuff) and 78% (medium cuff) to 79%
      (large cuff) of variance for upper and lower limbs, respectively. Adding DXA
      variables improved the explained variance up to 83% (small cuff) to 91% (medium
      cuff) and 79% (medium cuff) to 87% (large cuff) for upper and lower limbs,
      respectively. NIRS data showed significantly greater tissue oxygenation changes
      in upper versus lower limbs. CONCLUSIONS: The AOP in athletes is dependent on
      limb occluded, sex, SBP, limb and cuff size, and body composition.

PMID- 29341850
TI  - Clinical Inertia in a Randomized Trial of Telemedicine-Based Chronic Disease
      Management: Lessons Learned.
AB  - BACKGROUND: Treatment nonadherence and clinical inertia perpetuate poor
      cardiovascular disease (CVD) risk factor control. Telemedicine interventions may
      counter both treatment nonadherence and clinical inertia. INTRODUCTION: We
      explored why a telemedicine intervention designed to reduce treatment
      nonadherence and clinical inertia did not improve CVD risk factor control,
      despite enhancing treatment adherence versus usual care. METHODS: In this
      analysis of a randomized trial, we studied recipients of the 12-month
      telemedicine intervention. This intervention comprised two nurse-administered
      components: (1) monthly self-management education targeting improved treatment
      adherence; and (2) quarterly medication management facilitation designed to
      support treatment intensification by primary care (thereby reducing clinical
      inertia). For each medication management facilitation encounter, we ascertained
      whether patients met treatment goals, and if not, whether primary care
      recommended treatment intensification following the encounter. We assessed
      disease control associated with encounters, where intensification was/was not
      recommended. RESULTS: We examined 455 encounters across 182 intervention
      recipients (100% African Americans with type 2 diabetes). Even after accounting
      for valid reasons for deferring intensification (e.g., treatment nonadherence),
      intensification was not recommended in 67.5% of encounters in which hemoglobin
      A1c was above goal, 72.5% in which systolic blood pressure was above goal, and
      73.9% in which low-density lipoprotein cholesterol was above goal. In each
      disease state, treatment intensification was more likely with poorer control.
      CONCLUSIONS: Despite enhancing treatment adherence, this intervention was
      unsuccessful in countering clinical inertia, likely explaining its lack of effect
      on CVD risk factors. We identify several lessons learned that may benefit
      investigators and healthcare systems.

PMID- 29341852
TI  - Emissions of organic compounds from produced water ponds II: Evaluation of flux
      chamber measurements with inverse-modeling techniques.
AB  - : In this study, the authors apply two different dispersion models to evaluate
      flux chamber measurements of emissions of 58 organic compounds, including C2-C11
      hydrocarbons and methanol, ethanol, and isopropanol from oil- and gas-produced
      water ponds in the Uintah Basin. Field measurement campaigns using the flux
      chamber technique were performed at a limited number of produced water ponds in
      the basin throughout 2013-2016. Inverse-modeling results showed significantly
      higher emissions than were measured by the flux chamber. Discrepancies between
      the two methods vary across hydrocarbon compounds and are largest in alcohols due
      to their physical chemistries. This finding, in combination with findings in a
      related study using the WATER9 wastewater emission model, suggests that the flux
      chamber technique may underestimate organic compound emissions, especially
      alcohols, due to its limited coverage of the pond area and alteration of
      environmental conditions, especially wind speed. Comparisons of inverse-model
      estimations with flux chamber measurements varied significantly with the
      complexity of pond facilities and geometries. Both model results and flux chamber
      measurements suggest significant contributions from produced water ponds to total
      organic compound emission from oil and gas productions in the basin.
      IMPLICATIONS: This research is a component of an extensive study that showed
      significant amount of hydrocarbon emissions from produced water ponds in the
      Uintah Basin, Utah. Such findings have important meanings to air quality
      management agencies in developing control strategies for air pollution in oil and
      gas fields, especially for the Uintah Basin in which ozone pollutions frequently
      occurred in winter seasons.

PMID- 29341853
TI  - Influence of high heat load on flow and containment of an inclined air-curtain
      (IAC) fume hood.
AB  - The inclined air-curtain (IAC) fume hood has been reported to have "almost null
      leakage"[1] at low suction flow rates when operated at regular temperatures.
      However, previous research has not investigated the performance or optimized
      operating parameters when a high heat load is used in the IAC fume hood. For the
      present work, the effects of a high heat load on the flow field and contaminant
      leakage characteristics of the IAC fume hood were examined. The heat load was
      supplied to an IAC hood according to the standard method of EN14175-7:2012. The
      laser-assisted smoke flow visualization technique was employed to identify the
      characteristic flow patterns. The standard tracer-gas concentration test method
      (EN14175-3:2003) was used to examine the leakage levels of the IAC fume hood
      under static conditions, sash movement, and simulated walk-by conditions. When
      the IAC fume hood was operated at a high heat load, the static test results
      showed negligibly small leakage levels at a face velocity greater than or equal
      to only 0.19 m/s (37.4 ft/min). The sash movement and simulated walk-by test
      results showed that to obtain negligibly small leakage levels at high heat load
      operation, the IAC fume hood required a face velocity greater than or equal to
      0.32 m/s (63 ft/min). In addition, the IAC fume hood exhibited a superior hood
      containment performance with low energy consumption when compared with
      conventional fume hoods operated at a high heat load.

PMID- 29341851
TI  - Underutilization of Supplemental Magnetic Resonance Imaging Screening Among
      Patients at High Breast Cancer Risk.
AB  - BACKGROUND: Women at high lifetime breast cancer risk may benefit from
      supplemental breast magnetic resonance imaging (MRI) screening, in addition to
      routine mammography screening for earlier cancer detection. MATERIALS AND
      METHODS: We performed a cross-sectional study of 422,406 women undergoing routine
      mammography screening across 86 Breast Cancer Surveillance Consortium (BCSC)
      facilities during calendar year 2012. We determined availability and use of on
      site screening breast MRI services based on woman-level characteristics,
      including >20% lifetime absolute risk using the National Cancer Institute risk
      assessment tool. Multivariate analyses were performed to determine
      sociodemographic characteristics associated with on-site screening MRI use.
      RESULTS: Overall, 43.9% (2403/5468) of women at high lifetime risk attended a
      facility with on-site breast MRI screening availability. However, only 6.6%
      (158/2403) of high-risk women obtained breast MRI screening within a 2-year
      window of their screening mammogram. Patient factors associated with on-site MRI
      screening use included younger (<40 years) age (odds ratio [OR] = 2.39, 95%
      confidence interval [CI]: 1.34-4.21), family history (OR = 1.72, 95% CI: 1.13
      2.63), prior breast biopsy (OR = 2.09, 95% CI: 1.22-3.58), and postsecondary
      education (OR = 2.22, 95% CI: 1.04-4.74). CONCLUSIONS: While nearly half of women
      at high lifetime breast cancer risk undergo routine screening mammography at a
      facility with on-site breast MRI availability, supplemental breast MRI remains
      widely underutilized among those who may benefit from earlier cancer detection.
      Future studies should evaluate whether other enabling factors such as formal risk
      assessment and patient awareness of high lifetime breast cancer risk can mitigate
      the underutilization of supplemental screening breast MRI.

PMID- 29341854
TI  - Separation of brown carbon from black carbon for IMPROVE and Chemical Speciation
      Network PM2.5 samples.
AB  - : The replacement of the Desert Research Institute (DRI) model 2001 with model
      2015 thermal/optical analyzers (TOAs) results in continuity of the long-term
      organic carbon (OC) and elemental carbon (EC) database, and it adds optical
      information with no additional carbon analysis effort. The value of
      multiwavelength light attenuation is that light absorption due to black carbon
      (BC) can be separated from that of brown carbon (BrC), with subsequent
      attribution to known sources such as biomass burning and secondary organic
      aerosols. There is evidence of filter loading effects for the 25% of all samples
      with the highest EC concentrations based on the ratio of light attenuation to EC.
      Loading corrections similar to those used for the seven-wavelength aethalometer
      need to be investigated. On average, nonurban Interagency Monitoring of PROtected
      Visual Environments (IMPROVE) samples show higher BrC fractions of short
      wavelength absorption than urban Chemical Speciation Network (CSN) samples, owing
      to greater influence from biomass burning and aged aerosols, as well as to higher
      primary BC contributions from engine exhaust at urban sites. Sequential samples
      taken during an Everglades National Park wildfire demonstrate the evolution from
      flaming to smoldering combustion, with the BrC fraction increasing as smoldering
      begins to dominate the fire event. IMPLICATIONS: The inclusion of seven
      wavelengths in thermal/optical carbon analysis of speciated PM2.5 (particulate
      matter with an aerodynamic diameter <=2.5 MUm) samples allows contributions from
      biomass burning and secondary organic aerosols to be estimated. This separation
      is useful for evaluating control strategy effectiveness, identifying exceptional
      events, and determining natural visibility conditions.

PMID- 29341855
TI  - Probabilistic assessment of the potential indoor air impacts of vent-free gas
      heating appliances in energy-efficient homes in the United States.
AB  - : Use of vent-free gas heating appliances for supplemental heating in U.S. homes
      is increasing. However, there is currently a lack of information on the potential
      impact of these appliances on indoor air quality for homes constructed according
      to energy-efficient and green building standards. A probabilistic analysis was
      conducted to estimate the impact of vent-free gas heating appliances on indoor
      air concentrations of carbon monoxide (CO), nitrogen dioxide (NO2), carbon
      dioxide (CO2), water vapor, and oxygen in "tight" energy-efficient homes in the
      United States. A total of 20,000 simulations were conducted for each Department
      of Energy (DOE) heating region to capture a wide range of home sizes, appliance
      features, and conditions, by varying a number of parameters, e.g., room volume,
      house volume, outdoor humidity, air exchange rates, appliance input rates
      (Btu/hr), and house heat loss factors. Predicted airborne levels of CO were below
      the U.S. Environmental Protection Agency (EPA) standard of 9 ppm for all modeled
      cases. The airborne concentrations of NO2 were below the U.S. Consumer Product
      Safety Commission (CPSC) guideline of 0.3 ppm and the Health Canada benchmark of
      0.25 ppm in all cases and were below the World Health Organization (WHO) standard
      of 0.11 ppm in 99-100% of all cases. Predicted levels of CO2 were below the
      Health Canada standard of 3500 ppm for all simulated cases. Oxygen levels in the
      room of vent-free heating appliance use were not significantly reduced. The great
      majority of cases in all DOE regions were associated with relative humidity (RH)
      levels from all indoor water vapor sources that were less than the EPA
      recommended 70% RH maximum to avoid active mold and mildew growth. The conclusion
      of this investigation is that when installed in accordance with the
      manufacturer's instructions, vent-free gas heating appliances maintain acceptable
      indoor air quality in tight energy-efficient homes, as defined by the standards
      referenced in this report. IMPLICATIONS: Probabilistic modeling of indoor air
      concentrations of carbon monoxide (CO), nitrogen dioxide (NO2), carbon dioxide
      (CO2), water vapor, and oxygen associated with use of vent-free gas heating
      appliances provides new data indicating that uses of these devices are consistent
      with acceptable indoor air quality in "tight" energy-efficient homes in the
      United States. This study will provide authoritative bodies such as the
      International Code Council with definitive information that will assist in the
      development of future versions of national building codes, and will provide
      evaluation of the performance of unvented gas heating products in energy
      conservation homes.

PMID- 29341857
TI  - Development of visibility forecasting modeling framework for the Lower Fraser
      Valley of British Columbia using Canada's Regional Air Quality Deterministic
      Prediction System.
AB  - : Visibility degradation, one of the most noticeable indicators of poor air
      quality, can occur despite relatively low levels of particulate matter when the
      risk to human health is low. The availability of timely and reliable visibility
      forecasts can provide a more comprehensive understanding of the anticipated air
      quality conditions to better inform local jurisdictions and the public. This
      paper describes the development of a visibility forecasting modeling framework,
      which leverages the existing air quality and meteorological forecasts from
      Canada's operational Regional Air Quality Deterministic Prediction System
      (RAQDPS) for the Lower Fraser Valley of British Columbia. A baseline model (GM
      IMPROVE) was constructed using the revised IMPROVE algorithm based on unprocessed
      forecasts from the RAQDPS. Three additional prototypes (UMOS-HYB, GM-MLR, GM-RF)
      were also developed and assessed for forecast performance of up to 48 hr lead
      time during various air quality and meteorological conditions. Forecast
      performance was assessed by examining their ability to provide both numerical and
      categorical forecasts in the form of 1-hr total extinction and Visual Air Quality
      Ratings (VAQR), respectively. While GM-IMPROVE generally overestimated extinction
      more than twofold, it had skill in forecasting the relative species contribution
      to visibility impairment, including ammonium sulfate and ammonium nitrate. Both
      statistical prototypes, GM-MLR and GM-RF, performed well in forecasting 1-hr
      extinction during daylight hours, with correlation coefficients (R) ranging from
      0.59 to 0.77. UMOS-HYB, a prototype based on postprocessed air quality forecasts
      without additional statistical modeling, provided reasonable forecasts during
      most daylight hours. In terms of categorical forecasts, the best prototype was
      approximately 75 to 87% correct, when forecasting for a condensed three-category
      VAQR. A case study, focusing on a poor visual air quality yet low Air Quality
      Health Index episode, illustrated that the statistical prototypes were able to
      provide timely and skillful visibility forecasts with lead time up to 48 hr.
      IMPLICATIONS: This study describes the development of a visibility forecasting
      modeling framework, which leverages the existing air quality and meteorological
      forecasts from Canada's operational Regional Air Quality Deterministic Prediction
      System. The main applications include tourism and recreation planning, input into
      air quality management programs, and educational outreach. Visibility forecasts,
      when supplemented with the existing air quality and health based forecasts, can
      assist jurisdictions to anticipate the visual air quality impacts as perceived by
      the public, which can potentially assist in formulating the appropriate air
      quality bulletins and recommendations.

PMID- 29341856
TI  - KIX domain of AtMed15a, a Mediator subunit of Arabidopsis, is required for its
      interaction with different proteins.
AB  - Med15 is an important subunit of Mediator Tail module and is characterized by a
      KIX domain present towards amino terminal. In yeast and metazoans, Med15 KIX
      domain has been found to interact with various transcription factors regulating
      several processes including carbohydrate metabolism, lipogenesis, stress response
      and multidrug resistance. Mechanism of Med15 functioning in Arabidopsis is
      largely unknown. In this study, interactome of KIX domain of Arabidopsis Med15,
      AtMed15a, was characterized. We found 45 proteins that interact with AtMed15a KIX
      domain, including 11 transcription factors, 3 single strand nucleic acid-binding
      proteins and 1 splicing factor. The third helix of the KIX domain was found to be
      involved in most of the interactions. Mapping of the regions participating in the
      interactions revealed that the activation domain of a transcription factor, UKTF1
      interacted with AtMed15a KIX domain. Thus, our results suggest that in
      Arabidopsis, activation domain of transcription factors target KIX domain of
      AtMed15a for their transcriptional responses.

PMID- 29341858
TI  - Respiratory assessment of refractory ceramic fibers in a heating technician
      population.
AB  - Refractory ceramic fibers (RCF) have been extensively used for insulation in
      condensing boilers. The aim of this study was to evaluate the respiratory
      exposure to these fibers among maintenance heating technicians. We first created
      a working group (Carsat Brittany and Finistere Occupational Health Services) and
      carried out a sampling strategy. Atmospheric measurements were done during work
      tasks, and filters were analyzed by phase contrast microscopy (PCM) and scanning
      electron microscopy (SEM) in French approved laboratories. Four companies were
      included for a total of 15 days of work. During those 15 workdays, 12 SEM and 21
      PCM samples were taken and analyzed. The phase contrast microscopy and SEM
      average results were 0.04 and 0.004 fibers/cm3, respectively. In conclusion, the
      study confirms heating technician RCF respiratory exposure during maintenance
      work for both condensation gas boilers and atmospheric boilers. Collective and
      individual prevention measures should be implemented along with appropriate
      medical follow-up.

PMID- 29341859
TI  - An indoor air quality evaluation in a residential retrofit project using spray
      polyurethane foam.
AB  - Understanding of indoor air quality (IAQ) during and after spray polyurethane
      foam (SPF) application is essential to protect the health of both workers and
      building occupants. Previous efforts such as field monitoring, micro
      chamber/spray booth emission studies, and fate/transport modeling have been
      conducted to understand the chemical exposure of SPF and guide risk mitigation
      strategies. However, each type of research has its limitation and can only reveal
      partial information on the relationship between SPF and IAQ. A comprehensive
      study is truly needed to integrate the experimental design and analytical testing
      methods in the field/chamber studies with the mathematical tools employed in the
      modeling studies. This study aims to bridge this gap and provide a more
      comprehensive understanding on the impact of SPF to IAQ. The field sampling plan
      of this research aims to evaluate the airborne concentrations of methylene
      diphenyl diisocyanate (MDI), formaldehyde, acetaldehyde, propionaldehyde, tris(1
      chlor-2-propyl)phosphate (TCPP), trans-1-chloro-3,3,3-trifluoropropene
      (SolsticeTM), and airborne particles. Modifications to existing MDI sampling and
      analytical methods were made so that level of quantification was improved. In
      addition, key fate and transport modeling input parameters such as air changes
      per hour and airborne particle size distribution were measured. More importantly,
      TCPP accumulation onto materials was evaluated, which is important to study the
      fate and transport of semi-volatile organic compounds. The IAQ results showed
      that after spray application was completed in the entire building, airborne
      concentrations decreased for all chemicals monitored. However, it is our
      recommendation that during SPF application, no one should return to the
      application site without proper personal protection equipment as long as there
      are active spray activities in the building. The comparison between this field
      study and a recent chamber study proved surface sorption and particle deposition
      is an important factor in determining the fate of airborne TCPP. The study also
      suggests the need for further evaluation by employing mathematical models,
      proving the data generated in this work as informative to industry and the
      broader scientific community.

PMID- 29341860
TI  - Risk management of free radicals involved in air travel syndromes by
      antioxidants.
AB  - Frequent air travelers and airplane pilots may develop various types of
      illnesses. The environmental risk factors associated with air travel syndromes
      (ATS) or air travel-related adverse health outcomes raised concerns and need to
      be assessed in the context of risk management and public health. Accordingly, the
      aim of the present review was to determine ATS, risk factors, and mechanisms
      underlying ATS using scientific data and information obtained from Medline,
      Toxline, and regulatory agencies. Additional information was also extracted from
      websites of organizations, such as the International Air Transport Association
      (IATA), International Association for Medical Assistance to Travelers (IAMAT),
      and International Civil Aviation Organization (ICAO). Air travelers are known to
      be exposed to environmental risk factors, including circadian rhythm disruption,
      poor cabin air quality, mental stress, high altitude conditions, hormonal
      dysregulation, physical inactivity, fatigue, biological infections, and alcoholic
      beverage consumption. Consequences of ATS attributed to air travel include sleep
      disturbances (e.g., insomnia), mental/physical stress, gastrointestinal
      disorders, respiratory diseases, circulatory-related dysfunction, such as cardiac
      arrest and thrombosis and, at worst, mechanical and terrorism-related airplane
      crashes. Thus safety measures in the cabin before or after takeoff are undertaken
      to prevent illnesses or accidents related to flight. In addition, airport
      quarantine systems are strongly recommended to prepare for any ultimate adverse
      circumstances. Routine monitoring of environmental risk factors also needs to be
      considered. Frequently, the mechanisms underlying these adverse manifestations
      involve free radical generation. Therefore, antioxidant supplementation may help
      to reduce or prevent adverse outcomes by mitigating health risk factors
      associated with free radical generation.

PMID- 29341861
TI  - Genome-wide survey reveals dynamic effects of folate supplement on DNA
      methylation and gene expression during C2C12 differentiation.
AB  - Folic acid supplements taken during pregnancy can prevent neural tube defects and
      other developmental abnormalities. Here, we explored the effects of folate
      supplementation on gene expression and DNA methylation during C2C12
      differentiation. Based on the folic acid concentration, this study comprised
      three groups: low folate (L), normal folate (N), and high-folate supplement (H).
      Our analyses revealed that differentiation and the mRNA expression of the gene
      myogenin in C2C12 cell were enhanced by folic acid; however, the overall
      methylation percentage in myogenin promoter between different treatment groups
      was not significantly different ( P > 0.05). The results of MeDIP-chip showed
      that hundreds of differentially methylated regions (DMRs) were identified between
      every two groups in both promoter and CpG islands, respectively. Genes with DMRs
      between N and L groups were mainly enriched in the processes of cell
      differentiation and cell development, whereas those with DMRs between H and N
      groups were frequently enriched in cellular process/cycle and cell metabolic
      processes. In addition, correlation analysis between methylation profile and
      expression profile revealed that some genes were regulated by methylation status
      directly. Together, these analyses suggest that folate deficiency and
      supplementation can influence the differentiation, genome-wide DNA methylation
      level and the expression of myogenesis-related genes including myogenin in the
      C2C12 cell line.

PMID- 29341862
TI  - Identification of three genetic variants as novel susceptibility loci for body
      mass index in a Japanese population.
AB  - Recent genome-wide association studies have identified various obesity or
      metabolic syndrome (MetS) susceptibility loci. However, most studies were
      conducted in a cross-sectional manner. To address this gap, we performed a
      longitudinal exome-wide association study to identify susceptibility loci for
      obesity and MetS in a Japanese population. We traced clinical data of 6,022
      Japanese subjects who had annual health check-ups for several years (mean follow
      up period, 5 yr) and genotyped ~244,000 genetic variants. The association of
      single nucleotide polymorphisms (SNPs) with body mass index (BMI) or the
      prevalence of obesity and MetS was examined in a generalized estimating equation
      model. Our longitudinal exome-wide association studies detected 21 BMI- and five
      MetS-associated SNPs (false discovery rate, FDR <0.01). Among these SNPs, 16 have
      not been previously implicated as determinants of BMI or MetS. Cross-sectional
      data for obesity- and MetS-related phenotypes in 7,285 Japanese subjects were
      examined in a replication study. Among the 16 SNPs, three ( rs9491140 ,
      rs145848316 , and rs7863248 ) were related to BMI in the replication cohort ( P <
      0.05). In conclusion, three SNPs [ rs9491140 of NKAIN2 (FDR = 0.003, P = 1.9 * 10
      5), rs145848316 of KMT2C (FDR = 0.007, P = 4.5 * 10-5), and rs7863248 of AGTPBP1
      (FDR = 0.006, P = 4.2 * 10-5)] were newly identified as susceptibility loci for
      BMI.

PMID- 29341863
TI  - Distinct gene signatures predict insulin resistance in young mice with high fat
      diet-induced obesity.
AB  - Highly inbred C57BL/6 mice show wide variation in their degree of insulin
      resistance in response to diet-induced obesity even though they are almost
      genetically identical. Here we employed transcriptional profiling by RNA
      sequencing (RNA-Seq) of visceral adipose tissue (VAT) and liver in young mice to
      determine how gene expression patterns correlate with the later development of
      high-fat diet (HFD)-induced insulin resistance in adulthood. To accomplish this
      goal, we partially removed and banked tissues from pubertal mice. Mice
      subsequently received HFD followed by metabolic phenotyping to identify two well
      defined groups of mice with either severe or mild insulin resistance. The
      remaining tissues were collected at study termination. We then applied RNA-Seq to
      generate transcriptome profiles associated with worsened insulin resistance
      before and after the initiation of HFD. We found 244 up- and 109 downregulated
      genes in VAT of the most insulin-resistant mice even before HFD exposure.
      Downregulated genes included serine protease inhibitor, major urinary protein,
      and complement genes; upregulated genes represented mostly muscle constituents.
      These gene families were also differentially expressed in VAT of mice with high
      or low insulin resistance after HFD. Inflammatory genes predicted insulin
      resistance in liver, but not in VAT. In contrast, when we compared VAT of all
      mice before and after HFD, differentially expressed genes were predominantly
      composed of immune response genes. These data show a distinct set of gene
      transcripts in young mice correlates with the severity of insulin resistance in
      adulthood, providing insight into the pathogenesis of insulin resistance in early
      life.

PMID- 29341864
TI  - Comparison of acute kidney injury of different etiology reveals in-common
      mechanisms of tissue damage.
AB  - Acute kidney injury (AKI) is a syndrome of reduced glomerular filtration rate and
      urine production caused by a number of different diseases. It is associated with
      renal tissue damage. This tissue damage can cause tubular atrophy and
      interstitial fibrosis that leads to nephron loss and progression of chronic
      kidney disease (CKD). This review describes the in-common mechanisms behind
      tissue damage in AKI caused by different underlying diseases. Comparing six high
      quality microarray studies of renal gene expression after AKI in disease models
      (gram-negative sepsis, gram-positive sepsis, ischemia-reperfusion, malignant
      hypertension, rhabdomyolysis, and cisplatin toxicity) identified 5,254
      differentially expressed genes in at least one of the AKI models; 66% of genes
      were found only in one model, showing that there are unique features to AKI
      depending on the underlying disease. There were in-common features in the form of
      four genes that were differentially expressed in all six models, 49 in at least
      five, and 215 were found in common between at least four models. Gene ontology
      enrichment analysis could be broadly categorized into the injurious processes
      hypoxia, oxidative stress, and inflammation, as well as the cellular outcomes of
      cell death and tissue remodeling in the form of epithelial-to-mesenchymal
      transition. Pathway analysis showed that MYC is a central connection in the
      network of activated genes in-common to AKI, which suggests that it may be a
      central regulator of renal gene expression in tissue injury during AKI. The
      outlining of this molecular network may be useful for understanding progression
      from AKI to CKD.

PMID- 29341865
TI  - Evidence of genetic predisposition for metabolically healthy obesity and
      metabolically obese normal weight.
AB  - Obesity has evolved into a global pandemic that constitutes a major threat to
      public health. The majority of obesity-related health care costs are due to
      cardiometabolic complications, such as insulin resistance, dyslipidemia, and
      hypertension, which are risk factors for Type 2 diabetes and cardiovascular
      disease. However, many obese individuals, often called metabolically healthy
      obese (MHO), seem to be protected from these cardiometabolic complications.
      Conversely, there is a group of individuals who suffer from cardiometabolic
      complications despite being of normal weight; a condition termed metabolically
      obese normal weight (MONW). Recent large-scale genomic studies have provided
      evidence that a number of genetic variants show an association with increased
      adiposity but a favorable cardiometabolic profile, an indicator for the genetic
      basis of the MHO and MONW phenotypes. Many of these loci are located in or near
      genes that implicate pathways involved in adipogenesis, fat distribution, insulin
      signaling, and insulin resistance. It has been suggested that a threshold for
      subcutaneous adipose tissue expandability may be at play in the manifestation of
      MHO and MONW, where expiry of adipose tissue storage capacity could lead to
      ectopic lipid accumulation in non-adipose tissues such as liver, muscle, heart,
      and pancreatic beta cells. Understanding the genetic aspects of the mechanisms
      that underpin MHO and MONW is crucial to define appropriate public health action
      points and to develop effective intervention measures.

PMID- 29341866
TI  - Identifying low-grade cellular rejection after heart transplantation in children
      by using gene expression profiling.
AB  - Endomyocardial biopsy (EMB) remains the gold standard for detecting rejection
      after heart transplantation but is costly and invasive. This study aims to
      distinguish no rejection (0R) from low-grade rejection (1R/2R) after heart
      transplantation in children by using global gene expression profiling in blood. A
      total of 106 blood samples with corresponding EMB from 18 children who underwent
      heart transplantation from 2011 to 2014 were analyzed (18
      baseline/pretransplantation samples, 88 EMB samples). Corresponding rejection
      grades for each blood sample were 0R in 39% (34/88), 1R in 51% (45/88), and 2R in
      10% (9/88). mRNA from each sample was sequenced. Differential expression analysis
      was performed at the gene level. A k-nearest neighbor (kNN) analysis was applied
      to the most differentially expressed (DE) genes to identify rejection after
      transplantation. Mean age at transplantation was 10.0 +/- 5.4 yr. Expression of B
      cell and T cell receptor sequences was used to measure the effect of
      posttransplantation immunosuppression. Follow-up samples had lower levels of
      immunoglobulin gene families compared with pretransplantation ( P < 3E-5) (lower
      numbers of activated B cells). T cell receptor alpha and beta gene families had
      decreased expression in 0R samples compared with pretransplantation ( P < 4E-5)
      but recovered to near baseline levels in 1R/2R samples. kNN using the most DE
      gene (MKS1) and k = 9 nearest neighbors correctly identified 83% (73/88) of 1R/2R
      compared with 0R by leave-one-out cross validation. Using a genomic approach we
      can distinguish low-grade cellular allograft rejection (1R/2R) from no rejection
      (0R) after heart transplantation in children despite a wide age range.

PMID- 29341868
TI  - Transcriptional evidence for cross talk between JA and ET or SA during root-knot
      nematode invasion in tomato.
AB  - studies have demonstrated that jasmonic acid (JA) reduces root-knot nematode
      (RKN) infections in tomato plants. RKN invasion is sensed by roots, and root
      derived JA signaling activates systemic defense responses, though this is poorly
      understood. Here, we investigate variations in the RKN-induced transcriptome in
      scion phloem between two tomato plant grafts: CM/CM ( Lycopersicum esculentum
      Mill. cv. Castlemart) and CM/ spr2 (a JA-deficient mutant). A total of 8,716
      genes were differentially expressed in the scion phloem of the plants with JA
      deficient rootstock via RNA sequencing. Among these genes, 535 upregulated and
      153 downregulated genes with high copy numbers were identified as significantly
      differentially expressed. Among them, 34 predicted transcription factor genes
      were identified. Additionally, we used real-time quantitative PCR to analyze the
      expression patterns of 42 genes involved in the JA, ethylene, or salicylic acid
      pathway in phloem under RKN infection. The results suggested that in the absence
      of JA signaling, the ET signaling pathway is enhanced after RKN infection;
      however, alterations in the SA signaling pathway were not observed.

PMID- 29341867
TI  - Genetic and microbiome influence on lipid metabolism and dyslipidemia.
AB  - Disruption in the metabolism of lipids is broadly classified under dyslipidemia
      and relates to the concentration of lipids in the blood. Dyslipidemia is a
      predictor of cardio-metabolic disease including obesity. Traditionally, the large
      interindividual variation has been related to genetic factors and diet. Genome
      wide association studies have identified over 150 loci related to abnormal lipid
      levels, explaining ~40% of the total variation. Part of the unexplained variance
      has been attributed to environmental factors including diet, but the extent of
      the dietary contribution remains unquantified. Furthermore, other factors are
      likely to influence lipid metabolism including the gut microbiome, which plays an
      important role in the digestion of different dietary components including fats
      and polysaccharides. Here we describe the contributing role of host genetics and
      the gut microbiome to dyslipidemia and discuss the potential therapeutic
      implications of advances in understanding the gut microbiome to the treatment of
      dyslipidemia.

PMID- 29341870
TI  - Easy or Hard: It Makes a Tremendous Difference.

PMID- 29341869
TI  - A Report of the 24th Annual Congress on Women's Health-Workshop on Transforming
      Women's Health: From Research to Practice.
AB  - Sex and gender are critical contributors to overall health and disease, and
      considering both in research informs the development of prevention strategies and
      treatment interventions for both men and women. The National Institutes of Health
      (NIH) Office of Research on Women's Health sponsored a preconference workshop on
      this topic at the 24th Annual Women's Health Congress, which was held in Crystal
      City, VA, in April 2016. The workshop featured presentations by NIH intramural
      and extramural scientists who presented data on a variety of topics including
      polycystic kidney disease, vaccine protection, depression, drug addiction, and
      cardiovascular disease. In this publication, we discuss the major points of each
      presentation and demonstrate the importance of considering sex and gender in
      biomedical research.

PMID- 29341872
TI  - A CqFerritin protein inhibits white spot syndrome virus infection via regulating
      iron ions in red claw crayfish Cherax quadricarinatus.
AB  - It is well known that iron is an essential element for all living organism. The
      intracellular iron availability is also important for the host's innate immune
      response to various pathogens, in which the iron homeostasis can be regulated by
      ferritin due to its iron storage property. In this study, a full-length cDNA
      sequence of ferritin (named as CqFerritin) was identified with 1410 bp from red
      claw crayfish Cherax quadricarinatus, which contained an open reading frame of
      513 bp, encoding 170 amino acids with a conserved ferritin domain. Tissue
      distribution analysis demonstrated that CqFerritin was widely expressed in
      various tissues with high presence in haemocyte, haematopoietic tissue (Hpt) and
      heart, while lowest expression in hepatopancreas. In addition, loss-of-function
      of CqFerritin by gene silencing resulted in significantly higher expression of an
      envelope protein VP28 of white spot syndrome virus (WSSV) in red claw crayfish
      Hpt cell cultures, indicating the potential antiviral response of CqFerritin. To
      further explore the effect on WSSV replication by CqFerritin, recombinant
      CqFerritin protein (rCqFerritin) was transfected into Hpt cells followed by WSSV
      infection. Importantly, the replication of WSSV was obviously decreased in Hpt
      cells if transfected with rCqFerritin protein, suggesting that CqFerritin had
      clearly negative effect on WSSV infection. Furthermore, intracellular
      accumulation of iron ions was found to promote the WSSV replication in a dose
      dependent manner, illustrating that the iron level regulated by CqFerritin was
      likely to be vital for WSSV infection in red claw crayfish. Taken together, these
      data suggest that CqFerritin plays an important role in immune defense against
      WSSV infection in a crustacean C. quadricarinatus.

PMID- 29341873
TI  - Differences in heart rate reserve of similar physical activities during work and
      in leisure time - A study among Danish blue-collar workers.
AB  - Recent studies suggest that while leisure-time physical activity (LTPA) promotes
      general health, engaging in occupational physical activity (OPA) may have
      negative health consequences. It has been hypothesized that the different health
      effects from OPA and LTPA can be explained by differences in physical activity
      (PA) intensity in these two domains. To assess the intensity of OPA and LTPA, we
      aimed to study the percentage heart rate reserve (%HRR) during similar types of
      OPA and LTPA during workdays. Data from the NOMAD study on Danish blue-collar
      workers (n=124) with objective measurements of PA (using accelerometers) and
      heart rate (using heart rate monitors) for 4 workdays were analysed. Activities
      of sitting, standing, moving, walking, and stair climbing were identified and
      %HRR in each of these activities was determined for work and leisure. %HRR was
      significantly higher during OPA than LTPA. These differences were more pronounced
      in men than in women. Although not statistically significant in the fully
      adjusted model, we found indications that these differences were more pronounced
      in those with low compared to high fitness. To our knowledge, this is the first
      study with objective measurements showing that %HRR is higher during the same
      gross-body postural activities when performed at work compared to leisure-time
      during workdays. This elevated intensity may help explaining the negative health
      consequences of engagement in high levels of OPA. Future guidelines should
      distinguish OPA from LTPA, possibly by advising workers to remain active during
      their leisure time, in particular when they are highly active at work.

PMID- 29341874
TI  - Validation of an ICD code for accurately identifying emergency department
      patients who suffer an out-of-hospital cardiac arrest.
AB  - AIM: International classification of disease (ICD-9) code 427.5 (cardiac arrest)
      is utilized to identify cohorts of patients who suffer out-of-hospital cardiac
      arrest (OHCA), though the use of ICD codes for this purpose has never been
      formally validated. We sought to validate the utility of ICD-9 code 427.5 by
      identifying patients admitted from the emergency department (ED) after OHCA.
      METHODS: Adult visits to a single ED between January 2007 and July 2012 were
      retrospectively examined and a keyword search of the electronic medical record
      (EMR) was used to identify patients. Cardiac arrest was confirmed; and ICD-9
      information and location of return of spontaneous circulation (ROSC) were
      collected. Separately, the EMR was searched for patients who received ICD-9 code
      427.5. The kappa coefficient (kappa) was calculated, as was the sensitivity and
      specificity of the code for identifying OHCA. RESULTS: The keyword search
      identified 1717 patients, of which 385 suffered OHCA and 333 were assigned the
      code 427.5. The agreement between ICD-9 code and cardiac arrest was excellent
      (kappa = 0.895). The ICD-9 code 427.5 was both specific (99.4%) and sensitive
      (86.5%). Of the 52 cardiac arrests that were not identified by ICD-9 code, 33%
      had ROSC before arrival to the ED. When searching independently on ICD-9 code,
      347 patients with ICD-9 code 427.5 were found, of which 320 were "true" arrests.
      This yielded a positive predictive value of 92% for ICD-9 code 427.5 in
      predicting OHCA. CONCLUSIONS: ICD-9 code 427.5 is sensitive and specific for
      identifying ED patients who suffer OHCA with a positive predictive value of 92%.

PMID- 29341875
TI  - Beyond JAAD April 2018: Articles of interest to dermatologists from the
      nondermatologic literature.

PMID- 29341876
TI  - Probing and characterizing the high specific sequences of ssDNA aptamer against
      SGIV-infected cells.
AB  - As the major viral pathogen of grouper aquaculture, Singapore grouper iridovirus
      (SGIV) has caused great economic losses in China and Southeast Asia. In the
      previous study, we have generated highly specific ssDNA aptamers against SGIV
      infected grouper spleen cells (GS) by Systematic Evolution of Ligands by
      Exponential Enrichment technology (SELEX), in which Q2 had the highest binding
      affinity of 16.43 nM. In this study, we would try to identify the specific
      sequences in the aptamer Q2 that exhibited the high binding affinity to SGIV
      infected cells by truncating the original Q2 into some different specific
      segments. We first evaluated the specificity and binding affinity of these
      truncated aptamers to SGIV-infected cells by flow cytometry, fluorescent imaging
      of cells and aptamer-based enzyme-linked apta-sorbent assay (ELASA). We then
      performed cytotoxicity analysis, assessment of the inhibitory effects upon SGIV
      infection and the celluar internalization kinetics of each truncated aptamer.
      Compared to the initial Q2, one of the truncated aptamer Q2-C5 showed a 3-fold
      increase in the binding affinity for SGIV-infected cells, and held more effective
      inhibitory effects, higher internalization kinetics and stability. Hence, the
      aptamer's truncated methods could be applied in the research of identifying
      aptamer's key sequences. The shorter, structure optimizing aptamer showed more
      excellent performance over the originally selected aptamer, which could
      potentially be applied in developing commercial detection probes for the early
      and rapid diagnosis of SGIV infection, and highly specific therapeutic drugs
      against SGIV infection.

PMID- 29341877
TI  - Characterizing the effects of insertion of a 5.2 kb region of a VACV genome,
      which contains known immune evasion genes, on MVA immunogenicity.
AB  - Modified Vaccinia virus Ankara (MVA) is an attenuated Vaccinia virus (VACV) that
      is a popular vaccine vector candidate against many different pathogens. Its
      replication-restricted nature makes it a safe vaccine. However, higher doses or
      multiple boosts of MVA are necessary to elicit an immune response similar to wild
      type VACV. Multiple strategies have been used to create modified MVA viruses that
      remain safe, but have increased immunogenicity. For example, one common strategy
      is to delete MVA immunomodulatory proteins in hopes of increasing the host immune
      response. Here, we take the opposite approach and examine, for the first time,
      how re-introduction of a 5.2 kb region of VACV DNA (that codes for multiple
      immunomodulatory proteins) into MVA alters viral immunogenicity. Since antigen
      presenting cells (APCs) are critical connectors between the innate and adaptive
      immune system, we examined the effect of MVA/5.2 kb infection in these cells in
      vitro. MVA/5.2 kb infection decreased virus-induced apoptosis and virus-induced
      NF-kappaB activation. MVA.5.2 kb infection decreased TNF production. However,
      MVA/5.2 kb infection did not alter APC maturation or IL-6 and IL-8 production in
      vitro. We further explored MVA/5.2 kb immunogenicity in vivo. VACV-specific CD8+
      T cells were decreased after in vivo infection with MVA/5.2 kb versus MVA,
      suggesting that the MVA/5.2 kb construct is less immunogenic than MVA. These
      results demonstrate the limitations of in vitro studies for predicting the
      effects of genetic manipulation of MVA on immunogenicity. Although MVA/5.2 kb did
      not enhance MVA's immunogenicity, this study examined an unexplored strategy for
      optimizing MVA, and the insight gained from these results can help direct how to
      modify MVA in the future.

PMID- 29341878
TI  - Concentrations of arsenic and lead in rice (Oryza sativa L.) in Iran: A
      systematic review and carcinogenic risk assessment.
AB  - Exposure to heavy metals such as arsenic (As), lead (Pb), and cadmium (Cd) in
      either the short or the long term can cause cancers in humans. Dietary intake and
      consumption of rice (Oryza sativa L.) is increasing in Iran, and several studies
      on the concentration of heavy metals in rice have been carried out in this
      country in recent years. In this perspective, the main objective of the present
      study was to investigate, even via a meta-analysis of the existing literature,
      the presence of As and Pb in rice from many geographical areas in Iran, as well
      as to estimate the carcinogenic risk of these heavy metals in rice consumers. The
      results of the present ten years-spanning systematic review indicate that 21
      reports, collecting a total of 2088 samples, were performed between 2008 and
      October 2017. The minimum and maximum concentration of As was observed in the
      Golestan area (0.01 +/- 0.01 mg/kg d.w) and the Gillan region (3 mg/kg d.w); and
      Pb in the Shahrekord (0.07 +/- 0.02 mg/kg d.w) and Mazandaran (35 mg/kg d.w). The
      meta-analysis of data showed that pooled concentration of As in the rice was 0.04
      (95%CI: 0.02-0.06 mg/kg d.w), which resulted lower than the National Standard
      (NS) limits. However, the pooled concentration of Pb in the rice was 0.38 (95%CI:
      0.25-0.5 mg/kg d.w), i.e., higher than NS limits. The heterogeneity was
      significant between As (I2 = 63%, P value = .003) and Pb (I2 = 96%, P value <
      .001) studies. The carcinogenic risk assessment showed that minimum and maximum
      incremental lifetime cancer risk (ILCR) of As was in the 45-54 (4.53 * 10-2) and
      15-24 (5.50 * 10-2) year age groups consumers; and Pb, 45-54 (2.442 * 10-3) and
      15-24 (2.96 * 10-3), respectively. The overall carcinogenesis risk of As (4.864 *
      10-2) was 18.5 times higher than Pb (2.623 * 10-3). All age groups consumers of
      rice content of As and Pb are at considerable carcinogenesis risk (ILCR > 10-3).
      Therefore a decreased level of heavy metals in rice cultivation should be
      encouraged and performed in next planning.

PMID- 29341880
TI  - Targetable long non-coding RNAs in cancer treatments.
AB  - Aberrant expression of many long non-coding RNAs has been observed in various
      types of cancer, implicating their crucial roles in tumorigenesis and cancer
      progression. Emerging knowledge with regard to the critical physiological and
      pathological roles of long non-coding RNAs in cancers makes them potential
      targets in cancer treatments. In this review, we present a summary of the
      relatively well studied long non-coding RNAs that are involved in oncogenesis and
      outline their functions and functional mechanisms. Recent findings that may be
      utilized in therapeutic intervention are also highlighted. With the fast
      development in nucleic acid-based therapeutic reagents that can target disease
      associated RNAs, lncRNAs should be explored as potential targets in cancer
      treatments.

PMID- 29341879
TI  - Mechanisms of mitochondrial toxicity of the kinase inhibitors ponatinib,
      regorafenib and sorafenib in human hepatic HepG2 cells.
AB  - Previous studies have shown that certain kinase inhibitors are mitochondrial
      toxicants. In the current investigation, we determined the mechanisms of
      mitochondrial impairment by the kinase inhibitors ponatinib, regorafenib, and
      sorafenib in more detail. In HepG2 cells cultured in galactose and exposed for 24
      h, all three kinase inhibitors investigated depleted the cellular ATP pools at
      lower concentrations than cytotoxicity occurred, compatible with mitochondrial
      toxicity. The kinase inhibitors impaired the activity of different complexes of
      the respiratory chain in HepG2 cells exposed to the toxicants for 24 h and in
      isolated mouse liver mitochondria exposed acutely. As a consequence, they
      increased mitochondrial production of ROS in HepG2 cells in a time- and
      concentration-dependent fashion and decreased the mitochondrial membrane
      potential concentration-dependently. In HepG2 cells exposed for 24 h, they
      induced mitochondrial fragmentation, lysosome content and mitophagy as well as
      mitochondrial release of cytochrome c, leading to apoptosis and/or necrosis. In
      conclusion, the kinase inhibitors ponatinib, regorafenib, and sorafenib impaired
      the function of the respiratory chain, which was associated with increased ROS
      production and a drop in the mitochondrial membrane potential. Despite activation
      of defense measures such as mitochondrial fission and mitophagy, some cells were
      liquidated concentration-dependently by apoptosis or necrosis. Mitochondrial
      dysfunction may represent a toxicological mechanism of hepatotoxicity associated
      with certain kinase inhibitors.

PMID- 29341881
TI  - Clinical Implications of Technological Advances in Screening for Atrial
      Fibrillation.
AB  - The incidence of atrial fibrillation (AF) continues to increase worldwide as
      people live longer. AF is the leading cause of stroke among patients older than
      75 years and is responsible for at least 15% of all strokes. Industry has
      responded to this problem with a plethora of monitoring devices. These include
      single lead ECG adhesive sensors, implantable loop recorders, smartphone
      attachments and wearables. This review will concentrate on clinical studies using
      these technologies. There are wearables including watches and watch-like devices
      that will be mentioned but these have not been validated for clinical use. This
      review will begin with a background regarding screening for AF and at the end
      present findings from Cardiac Implantable devices that could influence use of the
      new mobile health technologies.

PMID- 29341882
TI  - Development and evaluation of a website for surveillance of healthcare-associated
      urinary tract infections in Australia.
AB  - Phase II of the Surveillance to Reduce Urinary Tract Infections project piloted a
      website for point prevalence surveys of healthcare-associated (HAUTI) and
      catheter-associated urinary tract infection in Australian hospitals and aged care
      homes. This report describes development and evaluation of the website for online
      data collection. Evaluation findings from 38 data collectors indicated that most
      respondents found website registration and web form use easy (N = 22; 58% and N =
      16; 43%, respectively). The need for improved computer literacy skills and
      automated data systems were highlighted. This study demonstrated a novel approach
      for Australian HAUTI data collection; however, refinements are needed before
      national roll-out.

PMID- 29341883
TI  - Brain-region-specific Molecular Responses to Maternal Separation and Social
      Defeat Stress in Mice.
AB  - The association between stress and mental illness has been well documented, but
      the molecular consequences of repeated exposure to stress have not been
      completely identified. The present study sought to elucidate the combinatorial
      effects of early-life maternal separation stress and adult social defeat stress
      on alterations in signal transduction and gene expression that have been
      previously implicated in susceptibility to psychosocial stress. Molecular
      analyses were performed in the prelimbic/infralimbic cortex, amygdala, and
      nucleus accumbens, three brain regions that have been suggested to play critical
      roles in determining stress responses. The current data reveal that both maternal
      separation and social defeat significantly impact the expression of genes
      involved in histone methylation and the beta-catenin-, endogenous opioid-,
      neurotrophin-, and glucocorticoid signaling pathways. Although the effects of
      maternal separation and social defeat were largely non-overlapping, a subset of
      genes in each brain region were governed by additive, opposing, or other types of
      interactions between these stress paradigms, thus highlighting potential
      molecular mechanisms through which these stressors might coordinately regulate
      brain function and behavior.

PMID- 29341884
TI  - Acute Stress Persistently Alters Locus Coeruleus Function and Anxiety-like
      Behavior in Adolescent Rats.
AB  - Stress is a physiological state characterized by altered neuroendocrine
      signaling, behavioral arousal, and anxiety. Chronic or traumatic stress may
      predispose individuals for multiple somatic and psychiatric illnesses. The locus
      coeruleus (LC) is a major node in the stress response that integrates input from
      multiple stress responsive neural circuits and releases norepinephrine (NE)
      throughout the central nervous system (CNS) to promote vigilance and anxiety.
      Many mood disorders associated with prior stress are characterized by chronically
      altered noradrenergic signaling, yet the long-term impact of an acute stressor on
      LC function is not clear. To determine how acute stress could affect anxiety-like
      behavior as well as LC function at immediate and extended time points, rats
      underwent simultaneous exposure to physical restraint and predator odor. Rats
      underwent behavioral testing immediately or one week after stressor exposure and
      were then sacrificed for whole-cell patch-clamp recordings of LC neurons. Stress
      caused an immediate increase in anxiety-like behaviors in the elevated plus maze
      (EPM), as well decreased excitatory synaptic transmission and increased
      spontaneous discharge in LC neurons. These effects persisted for seven days after
      stress. Importantly, the excitability of LC neurons was increased one week post
      stress, but not immediately after, suggesting a long-term adaptation by the
      system. Rats tested in the open field one week after stress also showed increased
      anxiety-like behaviors. These findings show that a single acute stressor is
      capable of precipitating long-lasting changes in the LC function that may be
      related to some of the behavioral effects of stress, potentially contributing to
      stress-induced disease pathogenesis.

PMID- 29341885
TI  - Deletion of the Duffy antigen receptor for chemokines (DARC) promotes insulin
      resistance and adipose tissue inflammation during high fat feeding.
AB  - OBJECTIVE: Inflammation in adipose tissues in obesity promotes insulin resistance
      and metabolic disease. The Duffy antigen receptor for chemokines (DARC) is a
      promiscuous non-signaling receptor expressed on erythrocytes and other cell types
      that modulates tissue inflammation by binding chemokines such as monocyte
      chemoattractant protein-1 (MCP-1) and by acting as a chemokine reservoir. DARC
      allelic variants are common in humans, but the role of DARC in modulating obesity
      related metabolic disease is unknown. METHODS: We examined body weight gain,
      tissue adiposity, metabolic parameters and inflammatory marker expression in wild
      type and DARC knockout mice fed a chow diet (CD) and high fat diet (HFD).
      RESULTS: Compared to wild-type mice, HFD-fed DARC knockout mice developed glucose
      intolerance and insulin resistance independent of increases in body weight or
      adiposity. Interestingly, insulin sensitivity was also diminished in lean male
      DARC knockout mice fed a chow diet. Insulin production was not reduced by DARC
      gene deletion, and plasma leptin levels were similar in HFD fed wild-type and
      DARC knockout mice. MCP-1 levels in plasma rose significantly in the HFD fed wild
      type mice, but not in the DARC knockout mice. Conversely, adipose tissue MCP-1
      levels were higher, and more macrophage crown-like structures were detected, in
      the HFD fed DARC knockout mice as compared with the wild-type mice, consistent
      with augmented adipose tissue inflammation that is not accurately reflected by
      plasma levels of DARC-bound MCP-1 in these mice. CONCLUSIONS: These findings
      suggest that DARC regulates metabolic function and adipose tissue inflammation,
      which may impact obesity-related disease in ethnic populations with high
      frequencies of DARC allelic variants.

PMID- 29341886
TI  - Regulation of HSF1 protein stabilization: An updated review.
AB  - Heat shock factor 1 (HSF1) is a transcriptional factor that determines the
      efficiency of heat shock responses (HSRs) in the cell. Given its function has
      been extensively studied in recent years, HSF1 is considered a potential target
      for the treatment of disorders associated with protein aggregation. The activity
      of HSF1 is traditionally regulated at the transcriptional level in which the
      transactivation domain of HSF1 is modified by extensive array of pos
      translational modifications, such as phosphorylation, sumoylation, and
      acetylation. Recently, HSF1 is also reported to be regulated at the monomeric
      level. For example, in neurodegenerative disorders such as Huntington's disease
      and Alzheimer's disease the expression levels of the monomeric HSF1 are found to
      be reduced markedly. Methylene blue (MB) and riluzole, two clinical available
      drugs, increase the amount of the monomeric HSF1 in both cells and animals. Since
      the monomeric HSF1 not only determines the efficiency of HSRs, but exerts
      protective effects in a trimerization-independent manner, increasing the amount
      of the monomeric HSF1 via stabilization of HSF1 may be an alternative strategy
      for the amplification of HSR. However, to date we have no outlined knowledges
      about HSF1 protein stabilization, though studies regarding the regulation of the
      monomeric HSF1 have been documented in recent years. Here, we summarize the
      regulation of the monomeric HSF1 by some previously reported factors, such as
      synuclein, Huntingtin (Htt), TDP-43, unfolded protein response (UPR), MB and
      doxorubicin (DOX), as well as their possible mechanisms, aiming to push the
      understanding about HSF1 protein stabilization.

PMID- 29341887
TI  - Molecular Basis of Substrate Polyspecificity of the Candida albicans Mdr1p
      Multidrug/H+ Antiporter.
AB  - The molecular basis of polyspecificity of Mdr1p, a major drug/H+ antiporter of
      Candida albicans, is not elucidated. We have probed the nature of the drug
      binding pocket by performing systematic mutagenesis of the 12 transmembrane
      segments. Replacement of the 252 amino acid residues with alanine or glycine
      yielded 2/3 neutral mutations while 1/3 led to the complete or selective loss of
      resistance to drugs or substrates transported by the pump. Using the GlpT-based
      3D-model of Mdr1p, we roughly categorized these critical residues depending on
      their type and localization, 1 degrees / main structural impact ("S" group), 2
      degrees / exposure to the lipid interface ("L" group), 3 degrees / buried but not
      facing the main central pocket, inferred as critical for the overall H+/drug
      antiport mechanism ("M" group) and finally 4 degrees / buried and facing the main
      central pocket ("B" group). Among "B" category, 13 residues were essential for
      the large majority of drugs/substrates, while 5 residues were much substrate
      specific, suggesting a role in governing polyspecificity (P group). 3D
      superposition of the substrate-specific MFS Glut1 and XylE with the MDR substrate
      polyspecific MdfA and Mdr1p revealed that the B group forms a common substrate
      interaction core while the P group is only found in the 2 MDR MFS transporters,
      distributed into 3 areas around the B core. This specific pattern has let us to
      propose that the structural basis for polyspecificity of MDR MFS transporters is
      the extended capacity brought by residues located at the periphery of a binding
      core to accomodate compounds differing in size and type.

PMID- 29341888
TI  - Protection against the Neurotoxic Effects of beta-Amyloid Peptide on Cultured
      Neuronal Cells by Lovastatin Involves Elevated Expression of alpha7 Nicotinic
      Acetylcholine Receptors and Activating Phosphorylation of Protein Kinases.
AB  - The treatment of neurodegenerative diseases with statins has drawn increasing
      attention, but the related molecular mechanisms remain elusive. To examine the
      pleiotropic cholesterol-independent effects of statins in connection with the
      treatment of Alzheimer disease, we probed the influence of lovastatin on the
      metabolism of amyloid precursor protein (APP), expression of nicotinic
      acetylcholine receptors (nAChRs), and activity of mitogen-activated protein
      kinase (MAPK) in primary cultured neurons and SH-SY5Y cells overexpressing human
      APP670/671. Lovastatin attenuated the neurotoxic effects of beta-amyloid peptide
      (Abeta) and affected the metabolism of APP, reducing levels of Abeta1 to Abeta42
      and beta-site amyloid precursor protein-cleaving enzyme 1; enhancing those of
      alphaAPP, disintegrin metalloproteinase domain-containing protein 10, and beta
      site amyloid precursor protein-cleaving enzyme 2; and up-regulating expression of
      alpha7 nAChR and stimulating phosphorylation of extracellular signal-regulated
      kinase (ERK)1/2. Interestingly, methyllycaconitine, an antagonist of alpha7
      nAChR, attenuated this effect on alphaAPP, but not on phospho-ERK1/2; whereas
      U0126, an inhibitor of MAPK/ERK kinase/ERK, blocked both the elevated expression
      of alpha7 nAChR and enhanced secretion of alphaAPP. Our findings indicate that
      lovastatin up-regulates expression of alpha7 nAChR by a mechanism involving
      activation of the MAPK/ERK pathway, which may result in diminished production of
      Abeta.

PMID- 29341889
TI  - Adventitial Activation in the Pathogenesis of Injury-Induced Arterial Remodeling:
      Potential Implications in Transplant Vasculopathy.
AB  - Transplant vasculopathy is one of the major causes of chronic rejection after
      solid organ transplantation. The pathogenic mechanisms of transplant vasculopathy
      are still poorly understood. Herein, we summarize current evidence suggesting
      that activation of the tunica adventitia may be involved in the pathogenesis of
      transplant vasculopathy. Adventitia is an early responder to various vascular
      injuries and plays an integral role in eliciting vascular inflammation and
      remodeling. Accumulation of macrophages in the adventitia promotes the
      development of vascular remodeling by releasing a variety of paracrine factors
      that have profound impacts on vascular mural cells. Targeting adventitial
      macrophages has been shown to be effective for repressing transplantation-induced
      arterial remodeling in animal models. Adventitia also fosters angiogenesis, and
      neovascularization of the adventitial layer may facilitate the transport of
      inflammatory cells through the arterial wall. Further investigations are
      warranted to clarify whether inhibiting adventitial oxidative stress and/or
      adventitial neovascularization are better strategies for preventing transplant
      vasculopathy.

PMID- 29341890
TI  - Periodontal diseases and adverse pregnancy outcomes: Is there a role for vitamin
      D?
AB  - Studies have shown a relationship between maternal periodontal diseases (PDs) and
      premature delivery. PDs are commonly encountered oral diseases which cause
      progressive damage to the periodontal ligament and alveolar bones, leading to
      loss of teeth and oral disabilities. PDs also adversely affect general health by
      worsening of cardiovascular and metabolic diseases. Moreover, maternal PDs are
      thought to be related to increasing the frequency of preterm-birth with low birth
      weight (PBLBW) in new-borns. Prematurity and immaturity are the leading causes of
      prenatal and infant mortality and is a major public health problem around the
      world. Inflamed periodontal tissues generate significantly high levels of
      proinflammatory cytokines that may have systemic effects on the host mother and
      the fetus. In addition, the bacteria that cause PDs produce endotoxins which can
      harm the fetus. Furthermore, studies have shown that microorganisms causing PDs
      can get access to the bloodstream, invading uterine tissues, to induce PBLBW.
      Another likely mechanism that connects PDs with adverse pregnancy outcome is
      maternal vitamin D status. A role of inadequate vitamin D status in the genesis
      of PDs has been reported. Administration of vitamin D supplementation during
      pregnancy could reduce the risk of maternal infections and adverse pregnancy
      outcomes. As maternal PDs are significant risk factors for adverse pregnancy
      outcome, preventive antenatal care for pregnant women in collaboration with the
      obstetric and dental professions are required.

PMID- 29341891
TI  - Long-term treadmill exercise improves memory impairment through restoration of
      decreased synaptic adhesion molecule 1/2/3 induced by transient cerebral ischemia
      in the aged gerbil hippocampus.
AB  - Exercise improves cognitive impairments induced by transient cerebral ischemia,
      and modulates synaptic adhesion molecules. In this study, we investigated effects
      of long-term treadmill exercise on cognitive impairments and its relation to
      changes of synaptic cell adhesion molecule (SynCAM) 1/2/3 in the hippocampus
      after 5 min of transient cerebral ischemia in aged gerbils. Animals were assigned
      to sedentary and exercised groups, given treadmill exercise for 4 consecutive
      weeks from 5 days after transient ischemia, and evaluated cognitive function
      through passive avoidance test and Morris water maze test. SynCAM 2 protein
      levels were determined in the hippocampus by western blot. In addition, neuronal
      and synaptic changes were examined by NeuN immunohistochemistry, and SynCAM 1/2/3
      and MAP2 double immunofluorescence, respectively. We found that transient
      cerebral ischemia led to neuronal death in the CA1 area and dentate gyrus, and
      impaired -memory function; however, 4 weeks of treadmill exercise improved
      ischemia-induced memory impairment. In addition, SynCAM 1/2/3 and SynCAM 2
      expression in the hippocampus was significantly decreased in the sedentary group
      after transient cerebral ischemia; however, SynCAM 1/2/3 expressionand and SynCAM
      2 protein level was significantly increased in the ischemic group with exercise.
      These results suggest that long-term treadmill exercise improves memory
      impairment through the restoration of decreased SynCAM 1/2/3 expression in the
      hippocampus induced by transient cerebral ischemia in the aged gerbil.

PMID- 29341892
TI  - Premature aging in behavior and immune functions in tyrosine hydroxylase
      haploinsufficient female mice. A longitudinal study.
AB  - Aging is accompanied by impairment in the nervous, immune, and endocrine systems
      as well as in neuroimmunoendocrine communication. In this context, there is an
      age-related alteration of the physiological response to acute stress, which is
      modulated by catecholamine (CA), final products of the sympathetic-adreno
      medullary axis. The involvement of CA in essential functions of the nervous
      system is consistent with the neuropsychological deficits found in mice with
      haploinsufficiency (hemizygous; HZ) of tyrosine hydroxylase (TH) enzyme (TH-HZ).
      However, other possible alterations in regulatory systems have not been studied
      in these animals. The aim of the present work was to analyze whether adult TH-HZ
      female mice presented the impairment of behavioral traits and immunological
      responses that occurs with aging and whether they had affected their mean
      lifespan. ICR-CD1 female TH-HZ and wild type (WT) mice were used in a
      longitudinal study. Behavioral tests were performed on adult and old mice in
      order to evaluate their sensorimotor abilities and exploratory capacity, as well
      as anxiety-like behaviors. At the ages of 2 +/- 1, 4 +/- 1, 9 +/- 1, 13 +/- 1 and
      20 +/- 1 months, peritoneal leukocytes were extracted and several immune
      functions were assessed (phagocytic capacity, Natural Killer (NK) cytotoxicity,
      and lymphoproliferative response to lipopolysaccharide (LPS) and concanavalin A
      (ConA)). In addition, several oxidative stress parameters (catalase, glutathione
      reductase and glutathione peroxidase activities, and reduced glutathione (GSH)
      concentrations as antioxidant compounds as well as xanthine oxidase activity,
      oxidized glutathione (GSSG) concentrations, and GSSG/GSH ratio as oxidants) were
      analyzed. As inflammatory stress parameters TNF-alpha and IL-10 concentrations,
      and TNF-alpha/IL-10 ratios as inflammatory/anti-inflammatory markers, were
      measured. Animals were maintained in standard conditions until their natural
      death. The results indicate that adult TH-HZ mice presented worse sensorimotor
      abilities and exploratory capacity than their WT littermates as well as greater
      anxiety-like behaviors. With regards to the immune system, adult TH-HZ animals
      exhibited lower values of phagocytic capacity, NK cytotoxicity, and
      lymphoproliferative response to LPS and ConA than WT mice. Moreover, immune cells
      of TH-HZ mice showed higher oxidative and inflammatory stress than those of WT
      animals. Although these differences between TH-HZ and WT, in general, decreased
      with aging, this premature immunosenescence and impairment of behavior of TH-HZ
      mice was accompanied by a shorter mean lifespan in comparison to WT counterparts.
      In conclusion, haploinsufficiency of th gene in female mice appears to provoke
      premature aging of the regulatory systems affecting mean lifespan.

PMID- 29341893
TI  - Targeting BDNF modulation by plant glycosides as a novel therapeutic strategy in
      the treatment of depression.
AB  - Current therapies in clinical practice face strong criticism regarding their
      efficacy, and side effects, which forced the neuro-researchers to discover novel
      agents with different mechanistic insights. Glycosides are naturally-occurring
      plant secondary metabolites with significant medicinal potential and clinical
      scope as antidepressant. The aim of this review is to focus on the antidepressant
      effects of glycosides in preclinical studies, with an emphasis on the possible
      mechanisms. The literature search revealed that only a few phytoglycosides have
      been evaluated for their relevance in depression alleviation. Through preclinical
      tests, it has come forth that the efficacy is mediated by the modulation of brain
      derived neurotrophic factor (BDFN) in the hippocampus, that is known for
      promoting synaptic efficacy, neuronal connectivity and neuroplasticity. Thus,
      attempting the upregulation of BDNF expression by plant glycosides can be a novel
      therapeutic strategy for the treatment of depression. The outcome of this review
      can stimulate neuroscientists to evaluate plant-derived glycosides for the
      treatment of depression, as these structurally-complex and diverse molecules,
      might usher in a new paradigm in the treatment of depression, with a better
      efficacy and tolerability.

PMID- 29341894
TI  - Protective effects of antioxidin-RL from Odorrana livida against ultraviolet B
      irradiated skin photoaging.
AB  - The unavoidable daily exposure of the skin to ultraviolet (UV) B radiation is
      proven to have deleterious effects. The action mechanism of antioxidin-RL, an
      antioxidant peptide purified from skin secretions of frog Odorrana livida with
      amino acid sequence of AMRLTYNRPCIYAT, is well characterized by NMR titration and
      mutation based on ABTS+ scavenging activities. In order to explore the protective
      effects of antioxidin-RL against UVB-irradiated skin photoaging, cell uptake
      assay was used to detect the location of antioxidin-RL molecules serving various
      biological functions in the cells. The protective effects of antioxidin-RL on UVB
      induced response were examined in vitro and in vivo. Results showed that
      antioxidin-RL successfully penetrated the cell membrane and exerted a positive
      effect on cell migration. It also effectively inhibited the UVB-induced excessive
      production of ROS and prevented oxidative damage to DNAs and proteins. Moreover,
      the mRNA expressions of MMP-1, VEGF, COX-2, and pro-inflammatory cytokines, such
      as IL-6 and TNF-alpha in antioxidin-RL-treated HaCaT and HSF cells were
      significantly down-regulated whereas those of FGF, procollagen type I and TGF
      beta1 up-regulated. Antioxidin-RL effectively prevented UVB-induced erythema on
      mouse skin, thereby inhibiting UVB-induced skin thickening and inflammation and
      increasing collagen deposition as demonstrated by in vivo experiments. Hence, the
      novel antioxidant peptide antioxidin-RL can effectively reduce UVB-induced skin
      reactions in vivo and in vitro, providing potential molecules against UVB-induced
      inflammation and photoaging.

PMID- 29341895
TI  - Prenatal paracetamol exposure and child neurodevelopment: A review.
AB  - BACKGROUND: The non-prescription medication paracetamol (acetaminophen, APAP) is
      currently recommended as a safe pain and fever treatment during pregnancy.
      However, recent studies suggest a possible association between APAP use in
      pregnancy and offspring neurodevelopment. OBJECTIVES: To conduct a review of
      publications reporting associations between prenatal APAP use and offspring
      neurodevelopmental outcomes. METHODS: Relevant sources were identified through a
      key word search of multiple databases (Medline, CINAHL, OVID and TOXNET) in
      September 2016. All English language observational studies of pregnancy APAP and
      three classes of neurodevelopmental outcomes (autism spectrum disorder (ASD),
      attention deficit hyperactivity disorder (ADHD), and intelligence quotient (IQ))
      were included. One reviewer (AZB) independently screened all titles and
      abstracts, extracted and analyzed the data. RESULTS: 64 studies were retrieved
      and 55 were ineligible. Nine prospective cohort studies fulfilled all inclusion
      criteria. Data pooling was not appropriate due to heterogeneity in outcomes. All
      included studies suggested an association between prenatal APAP exposure and the
      neurodevelopmental outcomes; ADHD, ASD, or lower IQ. Longer duration of APAP use
      was associated with increased risk. Associations were strongest for hyperactivity
      and attention-related outcomes. Little modification of associations by indication
      for use was reported. CONCLUSIONS: Together, these nine studies suggest an
      increased risk of adverse neurodevelopmental outcomes following prenatal APAP
      exposure. Further studies are urgently needed with; precise indication of use and
      exposure assessment of use both in utero and in early life. Given the current
      findings, pregnant women should be cautioned against indiscriminate use of APAP.
      These results have substantial public health implications.

PMID- 29341896
TI  - Luteinizing hormone signaling phosphorylates and activates the cyclic GMP
      phosphodiesterase PDE5 in mouse ovarian follicles, contributing an additional
      component to the hormonally induced decrease in cyclic GMP that reinitiates
      meiosis.
AB  - Prior to birth, oocytes within mammalian ovarian follicles initiate meiosis, but
      then arrest in prophase until puberty, when with each reproductive cycle, one or
      more follicles are stimulated by luteinizing hormone (LH) to resume meiosis in
      preparation for fertilization. Within preovulatory follicles, granulosa cells
      produce high levels of cGMP, which diffuses into the oocyte to maintain meiotic
      arrest. LH signaling restarts meiosis by rapidly lowering the levels of cGMP in
      the follicle and oocyte. Part of this decrease is mediated by the
      dephosphorylation and inactivation the NPR2 guanylyl cyclase in response to LH,
      but the mechanism for the remainder of the cGMP decrease is unknown. At least one
      cGMP phosphodiesterase, PDE5, is activated by LH signaling, which would
      contribute to lowering cGMP. PDE5 exhibits increased cGMP-hydrolytic activity
      when phosphorylated on serine 92, and we recently demonstrated that LH signaling
      phosphorylates PDE5 on this serine and increases its activity in rat follicles.
      To test the extent to which this mechanism contributes to the cGMP decrease that
      restarts meiosis, we generated a mouse line in which serine 92 was mutated to
      alanine (Pde5-S92A), such that it cannot be phosphorylated. Here we show that
      PDE5 phosphorylation is required for the LH-induced increase in cGMP-hydrolytic
      activity, but that this increase has only a modest effect on the LH-induced cGMP
      decrease in mouse follicles, and does not affect the timing of meiotic
      resumption. Though we show that the activation of PDE5 is among the mechanisms
      contributing to the cGMP decrease, these results suggest that another cGMP
      phosphodiesterase is also activated by LH signaling.

PMID- 29341897
TI  - Toxicity and toxicokinetics of Amanita exitialis in beagle dogs.
AB  - In this study, the toxicology of A. exitialis, a lethal mushroom found in China,
      and the toxicokinetics of peptide toxins contained in it were evaluated. Beagles
      were fed A. exitialis powder (20 or 60 mg/kg) in starch capsules, after which
      they were assessed for signs of toxicity, as well as biochemical and pathological
      changes. Ultra-performance liquid chromatography-electrospray ionization-tandem
      mass spectrometry was used to assay the peptide toxins. The total peptide toxins
      in A. exitialis was 3482.6 +/- 124.94 mg/kg. The beagles showed signs of
      toxicity, such as vomiting and diarrhea, at 12-48 h following ingestion of A.
      exitialis. Furthermore, alanine transaminase and aspartate transaminase levels in
      plasma, as well as prothrombin time and activated partial thromboplastin time
      peaked at 36 h post A. exitialis ingestion. Furthermore, total bilirubin and
      alkaline phosphatase levels peaked at 48 h after A. exitialis ingestion. Three
      dogs that were administered 60 mg/kg A. exitialis died at 24-72 h after ingesting
      the capsules. Additionally, liver histopathological examinations showed
      hemorrhagic necrosis of hepatocytes. alpha-Amanitin, beta-amanitin, and
      phallacidin were rapidly absorbed and eliminated from plasma after A. exitialis
      was ingested. A long latency period (12-24 h post A. exitialis ingestion) was
      observed in the dogs before the onset of gastrointestinal symptoms. There was
      acute liver damage thereafter. Gastric lavage and enhanced plasma clearance
      methods such as hemodialysis, hemoperfusion, or plasma exchange may be
      ineffective in removing amatoxins from blood at 12 h post A. exitialis ingestion.
      Enhanced excretion of amatoxins in urine could be effective within 2 days after
      ingestion of A. exitialis because amatoxins in 0-2 d urine accounted for more
      than 90% of the total urine excretion.

PMID- 29341899
TI  - Accurate prediction of vaccine stability under real storage conditions and during
      temperature excursions.
AB  - Due to their thermosensitivity, most vaccines must be kept refrigerated from
      production to use. To successfully carry out global immunization programs,
      ensuring the stability of vaccines is crucial. In this context, two important
      issues are critical, namely: (i) predicting vaccine stability and (ii) preventing
      product damage due to excessive temperature excursions outside of the recommended
      storage conditions (cold chain break). We applied a combination of advanced
      kinetics and statistical analyses on vaccine forced degradation data to
      accurately describe the loss of antigenicity for a multivalent freeze-dried
      inactivated virus vaccine containing three variants. The screening of large
      amounts of kinetic models combined with a statistical model selection approach
      resulted in the identification of two-step kinetic models. Predictions based on
      kinetic analysis and experimental stability data were in agreement, with
      approximately five percentage points difference from real values for long-term
      stability storage conditions, after excursions of temperature and during
      experimental shipments of freeze-dried products. Results showed that modeling a
      few months of forced degradation can be used to predict various time and
      temperature profiles endured by vaccines, i.e. long-term stability, short time
      excursions outside the labeled storage conditions or shipments at ambient
      temperature, with high accuracy. Pharmaceutical applications of the presented
      kinetics-based approach are discussed.

PMID- 29341898
TI  - Induction of alpha-synuclein pathology in the enteric nervous system of the rat
      and non-human primate results in gastrointestinal dysmotility and transient CNS
      pathology.
AB  - Alpha-Synuclein (alpha-syn) is by far the most highly vetted pathogenic and
      therapeutic target in Parkinson's disease. Aggregated alpha-syn is present in
      sporadic Parkinson's disease, both in the central nervous system (CNS) and
      peripheral nervous system (PNS). The enteric division of the PNS is of particular
      interest because 1) gastric dysfunction is a key clinical manifestation of
      Parkinson's disease, and 2) Lewy pathology in myenteric and submucosal neurons of
      the enteric nervous system (ENS) has been referred to as stage zero in the Braak
      pathological staging of Parkinson's disease. The presence of Lewy pathology in
      the ENS and the fact that patients often experience enteric dysfunction before
      the onset of motor symptoms has led to the hypothesis that alpha-syn pathology
      starts in the periphery, after which it spreads to the CNS via interconnected
      neural pathways. Here we sought to directly test this hypothesis in rodents and
      non-human primates (NHP) using two distinct models of alpha-syn pathology: the
      alpha-syn viral overexpression model and the preformed fibril (PFF) model.
      Subjects (rat and NHP) received targeted enteric injections of PFFs or adeno
      associated virus overexpressing the Parkinson's disease associated A53T alpha-syn
      mutant. Rats were evaluated for colonic motility monthly and sacrificed at 1, 6,
      or 12 months, whereas NHPs were sacrificed 12 months following inoculation, after
      which the time course and spread of pathology was examined in all animals. Rats
      exhibited a transient GI phenotype that resolved after four months. Minor alpha
      syn pathology was observed in the brainstem (dorsal motor nucleus of the vagus
      and locus coeruleus) 1 month after PFF injections; however, no pathology was
      observed at later time points (nor in saline or monomer treated animals).
      Similarly, a histopathological analysis of the NHP brains revealed no pathology
      despite the presence of robust alpha-syn pathology throughout the ENS which
      persisted for the entirety of the study (12 months). Our study shows that
      induction of alpha-syn pathology in the ENS is sufficient to induce GI
      dysfunction. Moreover, our data suggest that sustained spread of alpha-syn
      pathology from the periphery to the CNS and subsequent propagation is a rare
      event, and that the presence of enteric alpha-syn pathology and dysfunction may
      represent an epiphenomenon.

PMID- 29341901
TI  - A small peptide derived from BMP-9 can increase the effect of bFGF and NGF on SH
      SY5Y cells differentiation.
AB  - The current aging of the world population will increase the number of people
      suffering from brain degenerative diseases such as Alzheimer's disease (AD).
      There are evidence showing that the use of growth factors such as BMP-9 could
      restored cognitive function as it acts on many AD hallmarks at the same time.
      However, BMP-9 is a big protein expensive to produce that can hardly access the
      central nervous system. We have therefore developed a small peptide, SpBMP-9,
      derived from the knuckle epitope of BMP-9 and showed its therapeutic potential in
      a previous study. Since it is known that the native protein, BMP-9, can act in
      synergy with other growth factors in the context of AD, here we study the
      potential synergistic effect of various combinations of SpBMP-9 with bFGF, EGF,
      IGF-2 or NGF on the cholinergic differentiation of human neuroblastoma cells SH
      SY5Y. We found that, in opposition to IGF-2 or EGF, the combination of SpBMP-9
      with bFGF or NGF can stimulate to a greater extent the neurite outgrowth and
      neuronal differentiation toward the cholinergic phenotype as shown by expression
      and localization of the neuronal markers NSE and VAchT and the staining of
      intracellular calcium. Those results strongly suggest that SpBMP-9 plus NGF or
      bFGF are promising therapeutic combinations against AD that required further
      attention.

PMID- 29341900
TI  - Lamotrigine loaded poly-E-(d,l-lactide-co-caprolactone) nanoparticles as brain
      delivery system.
AB  - Management of epilepsy requires brain delivery therapy, therefore, this study was
      aimed to prepare lamotrigine loaded poly-E-(d,l-lactide-co-caprolactone) (PLCL)
      nanoparticles using spontaneous emulsification solvent diffusion method.
      Nanoparticles for brain delivery required to have a particle size <200 nm,
      polydispesity index <0.2 and a sustained drug release properties. For such aim
      different factors were considered in preparing the nanoparticles as PLCL
      monomers' ratio, type of organic solvent used to prepare the nanoparticles,
      amount of PLCL and Pluronic(r)F127 in the nanoparticles. Prepared nanoparticles
      were characterized for their shape, particle size, polydispersity index, zeta
      potential, encapsulation efficiency, drug loading capacity, process yield and in
      vitro drug release pattern. The in-vivo investigation for brain delivery of
      selected nanoparticles delivered by intravenous route was investigated in rats
      and compared to that for oral tablet. The obtained nanoparticles were spherical
      in shape. The amount of surfactant and PLCL affected the properties of the
      obtained nanoparticles. Using a mixture of organic solvent in preparing the
      nanoparticles improved its properties. The nanoparticles prepared using PLCL with
      monomers' ratio of 25:75, had particle size value of 125 nm, polydispersity index
      value of 0.184, zeta potential value of -39 mV and encapsulation efficiency value
      of 99%, was selected to study their efficacy to deliver the drug to the brain.
      The tested nanoparticles showed higher values of Tmax, Cmax, AUC, and MRT in
      homogenized rat brain, compared to oral lamotrigine tablet, while the
      bioavailability of the oral tablet was higher in rat plasma compared to that for
      the nanoparticles. This reflects that brain was the main distribution site for
      tested nanoparticles, and plasma was the main distribution site for oral tablets.
      This confirms the goal of the selected formulation as brain delivery
      nanoparticles.

PMID- 29341902
TI  - Curcumin potentiates the function of human alpha7-nicotinic acetylcholine
      receptors expressed in SH-EP1 cells.
AB  - Effects of curcumin, a biologically active ingredient of turmeric, were tested on
      the Ca2+ transients induced by the activation of alpha7 subunit of the human
      nicotinic acetylcholine (alpha7 nACh) receptor expressed in SH-EP1 cells.
      Curcumin caused a significant potentiation of choline (1 mM)-induced Ca2+
      transients with an EC50 value of 133 nM. The potentiating effect of curcumin was
      not observed in Ca2+ transients induced by high K+ (60 mM) containing solutions
      or activation of alpha4beta2 nACh receptors and the extent of curcumin
      potentiation was not altered in the presence of Ca2+ channel antagonists
      nifedipine (1 MUM), verapamil (1 MUM), omega-conotoxin (1 MUM), and bepridil (10
      MUM). Noticeably the effect of curcumin was not observed when curcumin and
      choline were co-applied without curcumin pre-incubation. The effect of curcumin
      on choline-induced Ca2+ transients was not reversed by pre-incubation with
      inhibitors of protein C, A, and CaM kinases. Metabolites of curcumin such as
      tetrahydrocurcumin, demethylcurcumin, and didemethylcurcumin also caused
      potentiation of choline-induced Ca2+ transients. Notably, specific binding of
      [125I]-bungarotoxin was not altered in the presence of curcumin. Collectively,
      our results indicate that curcumin allosterically potentiate the function of the
      alpha7-nACh receptor expressed in SH-EP1 cells.

PMID- 29341903
TI  - Emerging roles and mechanisms of FOXC2 in cancer.
AB  - Forkhead box protein C2 (FOXC2), a transcription factor of the forkhead/winged
      helix family, is required for embryonic and prenatal development. FOXC2 acts as a
      crucial modulator during both angiogenesis and lymphangiogenesis via multiple
      angiogenic and lymphangiogenic pathways, respectively. Although recent studies
      have shed light on the emerging role of FOXC2 in cancer, very little is known
      about the precise underlying mechanisms. The purpose of this review is to
      summarize the current understanding of FOXC2 and provide potential mechanistic
      explanations of the relationship between FOXC2 and cancer, as well as discuss the
      prospect for future research in the promising prognostic value of FOXC2 in
      cancer.

PMID- 29341904
TI  - A rapid and simple LC-MS/MS method for personalized busulfan dosing in pediatric
      patients undergoing hematopoietic stem cell transplantation (HSCT).
AB  - BACKGROUND: Busulfan is commonly used as a conditioning regimen before
      hematopoietic stem cell transplantation (HSCT). There is a big inter-individual
      variability in busulfan exposure and the narrow therapeutic index, especially in
      pediatric population. Therefore, to achieve therapeutic efficacy and safety
      concurrently, personalized busulfan dosing, guided by pharmacokinetic study with
      serial plasma samples, is needed a few hours afterwards. METHODS: A fast,
      sensitive, and accurate method for busulfan measurement was developed, validated,
      and implemented with liquid-chromatography-mass spectrometry (HPLC-MS/MS). The
      sample preparation procedure involves only protein precipitation and dilution,
      and the HPLC-MS/MS method takes 3 min/sample. The assay was linear from 10 ng/ml
      to 7500 ng/ml (R2 = 0.99). Recoveries were above 90%. The precision was
      determined at 3 levels (30, 300 and 4000 ng/ml): the intra-day variability (%CV)
      ranged from 1.4% to 2.5% (n = 20); the inter-day variability ranged from 2.2% to
      5.5% (n = 20). The accuracy of the HPLC-MS/MS test was evaluated with an old HPLC
      fluorescence method (n = 84), and a Correlation Coefficient (R) of 0.99 was
      observed. CONCLUSIONS: The analytical performance of the assay allows for timely
      dose adjustment and has been implemented in clinical service for better clinical
      outcome.

PMID- 29341906
TI  - Lateralization of mother-infant interactions in wild horses.
AB  - The manifestation of behavioural lateralization has been shown to be modified by
      environmental conditions, life experiences, and selective breeding. This study
      tests whether the lateralization recently found in feral domestic horse (Equus
      caballus) is evident in undomesticated horses. Mother-offspring interactions were
      investigated in Przewalski's horse (E. ferus przewalskii) living in their natural
      habitat in Mongolia. Lateral position preferences during mare-foal spontaneous
      reunions were used as a behavioural marker of visual lateralization. Preferences
      were separately assessed for foals' approaches to their mothers and mares'
      approaches to their foals. Preference to keep the mother in the visual field of
      the left eye was found in various types of foals' behaviour. In slow travelling,
      Przewalski's foals showed stronger preference for the left eye use than feral
      horse foals. Population-level left-eye bias was also found in mothers approaching
      their foals. Our results indicate right-hemispheric dominance for control of
      mother-offspring interactions in Przewalski's horses, similar to what has been
      reported for other mammals including humans. Benefits conferred by the
      lateralized social processing of and responding to social stimuli may explain
      that the left-lateralized social behaviour is a robust trait of equine behaviour,
      not modified by domestication or specific environmental conditions of the
      population.

PMID- 29341905
TI  - Intensity difference limens in adult CBA/CaJ mice (Mus musculus).
AB  - Mice have emerged as important models of auditory perception and acoustic
      communication. To study and model complex sound perception and communication,
      basic hearing abilities have to be established, yet intensity difference limens
      have not been measured in CBA/CaJ mice. Nine mice were trained using operant
      conditioning procedures with positive reinforcement to discriminate sound
      intensity across frequencies. Intensity difference limens were measured for 12,
      16, 24, and 42 kHz tones at 10 and 30 dB sensation levels. Mice are capable of
      discriminating intensities across frequencies and sensation levels, but have
      higher intensity difference limens (IDLs) thresholds than other mammals.

PMID- 29341907
TI  - Molecular-level elucidation of saccharin-assisted rapid dissolution and high
      supersaturation level of drug from Eudragit(r) E solid dispersion.
AB  - In this work, the effect of saccharin (SAC) addition on the dissolution and
      supersaturation level of phenytoin (PHT)/Eudragit(r) E (EUD-E) solid dispersion
      (SD) at neutral pH was examined. The PHT/EUD-E SD showed a much slower
      dissolution of PHT compared to the PHT/EUD-E/SAC SD. EUD-E formed a gel layer
      after the dispersion of the PHT/EUD-E SD into an aqueous medium, resulting in a
      slow dissolution of PHT. Pre-dissolving SAC in the aqueous medium significantly
      improved the dissolution of the PHT/EUD-E SD. Solid-state 13C NMR measurements
      showed an ionic interaction between the tertiary amino group of EUD-E and the
      amide group of SAC in the EUD-E gel layer. Consequently, the ionized EUD-E could
      easily dissolve from the gel layer, promoting PHT dissolution. Solution-state 1H
      NMR measurements revealed the presence of ionic interactions between SAC and the
      amino group of EUD-E in the PHT/EUD-E/SAC solution. In contrast, interactions
      between PHT and the hydrophobic group of EUD-E strongly inhibited the
      crystallization of the former from its supersaturated solution. The PHT
      supersaturated solution was formed from the PHT/EUD-E/SAC SD by the fast
      dissolution of PHT and the strong crystallization inhibition effect of EUD-E
      after aqueous dissolution.

PMID- 29341908
TI  - Induction of Au-methotrexate conjugates by sugar molecules: production, assembly
      mechanism, and bioassay studies.
AB  - Au-methotrexate (Au-MTX) conjugates induced by sugar molecules were produced by a
      simple, one-pot, hydrothermal growth method. Herein, the Au(III)-MTX complexes
      were used as the precursors to form Au-MTX conjugates. Addition of different
      types of sugar molecules with abundant hydroxyl groups resulted in the formation
      of Au-MTX conjugates featuring distinct characteristics that could be explained
      by the diverse capping mechanisms of sugar molecules. That is, the instant
      capping mechanism of glucose favored the generation of peanut-like Au-MTX
      conjugates with high colloidal stability while the post-capping mechanism of
      dextran and sucrose resulted in the production of Au-MTX conjugates featuring
      excellent near-infrared (NIR) optical properties with a long-wavelength plasmon
      resonance near 630-760 nm. Moreover, in vitro bioassays showed that cancer cell
      viabilities upon incubation with free MTX, Au-MTX conjugates doped with glucose,
      dextran and sucrose for 48 h were 74.6%, 55.0%, 62.0%, and 63.1%, respectively.
      Glucose-doped Au-MTX conjugates exhibited a higher anticancer activity than those
      doped with dextran and sucrose, therefore potentially presenting a promising
      treatment platform for anticancer therapy. Based on the present study, this work
      may provide the first example of using biocompatible sugars as regulating agents
      to effectively guide the shape and assembly behavior of Au-MTX conjugates.
      Potentially, the synergistic strategy of drug molecules and sugar molecules may
      offer the possibility to create more gold-based nanocarriers with new shapes and
      beneficial features for advanced anticancer therapy.

PMID- 29341909
TI  - Nanogel-DFO conjugates as a model to investigate pharmacokinetics,
      biodistribution, and iron chelation in vivo.
AB  - Deferoxamine (DFO) to treat iron overload (IO) has been limited by toxicity
      issues and short circulation times and it would be desirable to prolong
      circulation to improve non-transferrin bound iron (NTBI) chelation. In addition,
      DFO is currently unable to efficiently target the large pool of iron in the liver
      and spleen. Nanogel-Deferoxamine conjugates (NG-DFO) can prove useful as a model
      to investigate the pharmacokinetic (PK) properties and biodistribution (BD)
      behavior of iron-chelating macromolecules and their overall effect on serum
      ferritin levels. NG-DFO reduced the cytotoxicity of DFO and significantly reduced
      cellular ferritin levels in IO macrophages in vitro. PK/BD studies in normal rats
      revealed that NG-DFO displayed prolonged circulation and preferential
      accumulation into the liver and spleen. IO mice treated with NG1-DFO presented
      significantly lower levels of serum ferritin compared to DFO. Total renal and
      fecal elimination data point to the need to balance prolonged circulation with
      controlled degradation to accelerate clearance of iron-chelating macromolecules.

PMID- 29341910
TI  - Isomalt and its diastereomer mixtures as stabilizing excipients with freeze-dried
      lactate dehydrogenase.
AB  - The purpose of this research was to study isomalt as a protein-stabilizing
      excipient with lactate dehydrogenase (LDH) during freeze-drying and subsequent
      storage and compare it to sucrose, a standard freeze-drying excipient. Four
      different diastereomer mixtures of isomalt were studied. The stability of the
      protein was studied with a spectrophotometric enzyme activity test and circular
      dichroism after freeze-drying and after 21 days of storage at 16% RH. Physical
      stability was analyzed with differential scanning calorimetry and Karl Fischer
      titration. Statistical analysis was utilized in result analysis. LDH activity was
      almost completely retained after freeze-drying with sucrose; whereas samples
      stabilized with isomalt diastereomer mixtures had a considerably lower protein
      activity. During storage the sucrose-containing samples lost most of their
      enzymatic activity, while the isomalt mixtures retained the protein activity
      better. In all cases changes to protein secondary structure were observed.
      Isomalt diastereomer mixtures have some potential as protein-stabilizing
      excipients during freeze-drying and subsequent storage. Isomalt stabilized LDH
      moderately during freeze-drying; however it performed better during storage.
      Future studies with other proteins are required to evaluate more generally
      whether isomalt would be a suitable excipient for pharmaceutical freeze-dried
      protein formulations.

PMID- 29341911
TI  - An efficient PEGylated gene delivery system with improved targeting: Synergism
      between octaarginine and a fusogenic peptide.
AB  - Because of their ability to translocate different cargos into cells, arginine
      rich cell penetrating peptides (CPPs) are promising vehicles for drug and gene
      delivery. The use of CPP-based carriers, however, is hampered by the lack of
      specificity and by interactions with negative serum components. Polyethylene
      glycol (PEG) is used to decrease such non-specific interactions, albeit its use
      is associated with reduced transfection efficiency. In this study, we describe
      the development of PEGylated CPP-based gene carrier with an improved targeting
      and a high transfection activity. The system was prepared by condensing DNA with
      a polycation followed by coating with a lipid envelope containing the
      octaarginine (R8) peptide as a model CPP. R8-modified nanoparticles produced high
      transfection activities, but the efficiency was reduced by PEG shielding. The
      reduced activity could be fully restored by the addition of a targeting ligand
      and a pH-sensitive fusogenic peptide. The efficiency of the proposed system is
      quite high, even in the presence of serum, and shows improved targeting and
      selectivity. Surprisingly, the effect of the fusogenic peptide was dramatically
      reduced in the absence of R8. Although shielded, R8 augmented the activity of the
      fusogenic peptide, suggesting a synergistic effect between the two peptides at
      the intracellular level.

PMID- 29341912
TI  - Quantitative estimation of phenytoin sodium disproportionation in the
      formulations using vibration spectroscopies and multivariate methodologies.
AB  - Phenytoin sodium (PS) has a tendency to convert to its base form; phenytoin base
      (PHT) during manufacturing, packaging, shelf life and in-use conditions that can
      influence its clinical performance. The objective of the present work was to
      develop a non-destructive, quick and easy analytical method for quantification of
      PHT in the drug product. A formulation was prepared to contain the excipients of
      commercial capsule formulation of PS. The formulation containing either 100% PHT
      or PS was prepared and these formulations were mixed in different proportion to
      achieve 0-100% PHT matrices. FTIR, NIR and Raman spectra of samples were
      collected. Data were truncated and mathematically pretreated before development
      of partial least squares (PLS) and principal component analysis (PCA) regressions
      model. The models were assessed by slope, intercept, R, R2, root mean square
      error (RMSE) and standard error (SEP). The models exhibited good linearity over
      the selected range of PHT in the formulations with low error as indicated by
      slope that was close to one and small values of intercept, RMSE and SE. The
      models of NIR based data were more accurate and precise than Raman data based
      models as indicated by the low values of RMSE and SE. Prediction accuracy of
      independent samples containing 25% PHT using NIR models were similar to Raman
      models. On the other hand, the prediction was more precise for the independent
      sample containing 5% PHT using NIR data based models compared to Raman data based
      models as indicated by standard deviation. In conclusion, chemometric models
      based on NIR and Raman spectroscopies provides a fast and easy way to monitor the
      disproportionation of PS in the drug products.

PMID- 29341913
TI  - Characterisation of pore structures of pharmaceutical tablets: A review.
AB  - Traditionally, the development of a new solid dosage form is formulation-driven
      and less focus is put on the design of a specific microstructure for the drug
      delivery system. However, the compaction process particularly impacts the
      microstructure, or more precisely, the pore architecture in a pharmaceutical
      tablet. Besides the formulation, the pore structure is a major contributor to the
      overall performance of oral solid dosage forms as it directly affects the liquid
      uptake rate, which is the very first step of the dissolution process. In future,
      additive manufacturing is a potential game changer to design the inner structures
      and realise a tailor-made pore structure. In pharmaceutical development the pore
      structure is most commonly only described by the total porosity of the tablet
      matrix. Yet it is of great importance to consider other parameters to fully
      resolve the interplay between microstructure and dosage form performance.
      Specifically, tortuosity, connectivity, as well as pore shape, size and
      orientation all impact the flow paths and play an important role in describing
      the fluid flow in a pharmaceutical tablet. This review presents the key
      properties of the pore structures in solid dosage forms and it discusses how to
      measure these properties. In particular, the principles, advantages and
      limitations of helium pycnometry, mercury porosimetry, terahertz time-domain
      spectroscopy, nuclear magnetic resonance and X-ray computed microtomography are
      discussed.

PMID- 29341914
TI  - Is there a correlation between the glass forming ability of a drug and its
      supersaturation propensity?
AB  - The use of an enabling formulation technique, such as amorphization of a poorly
      water-soluble crystalline drug, can result in supersaturation with respect to the
      crystalline form of the drug and thus potentially in a higher degree of
      absorption after oral administration. The ease with which such drugs can be
      amorphized is known as their glass forming ability (GFA). In this study, a
      potential correlation between GFA and supersaturation propensity is investigated.
      The GFA of 23 different drugs was determined by melt quenching or milling the
      crystalline drugs to obtain their respective amorphous forms. The inherent
      propensity of the drug to supersaturate, i.e. the maximal apparent degree of
      supersaturation (aDS), and the time until precipitation at a given aDS were
      determined. Supersaturation was induced via a solvent shift method where the drug
      was initially dissolved in dimethyl sulfoxide and then added to a biorelevant
      medium (fasted state simulated intestinal fluid).The study showed that drugs
      which are good glass formers also have the potential to supersaturate to a high
      degree (high maximal aDS) whereas drugs that are modest glass formers
      supersaturate only to a low degree. This correlation was confirmed by principal
      component analysis, which also indicated that melt enthalpy inversely correlated
      with both GFA and maximal aDS. However, no correlation between GFA of a drug and
      the time until precipitation at a given aDS was found.

PMID- 29341915
TI  - Influence of ligands property and particle size of gold nanoparticles on the
      protein adsorption and corresponding targeting ability.
AB  - Nanoparticulated vesicles were widely used for carriers of drugs and imaging
      probes. To improve the targeting delivery efficiency of these vesicles, ligands
      were often functionalized onto their surfaces. However, the interaction between
      vesicles and plasma proteins may cover the ligands and hinder the targeting
      delivery. It is important to address the potential influence of ligands
      modification on plasma protein adsorption and the following targeting delivery.
      In this study, two common used ligands were chosen as the model: transferrin and
      RGD peptide. Gold nanoparticles were utilized as model particles. Sodium dodecyl
      sulfate polyacrylamide gel electrophoresis data demonstrated that higher PEG
      modification and smaller particle size could reduce the plasma protein
      adsorption, while ligand modification could increase. The cellular uptake results
      showed that the targeting ability of smaller ligand RGD peptide would be more
      easily influenced by the proteins corona.

PMID- 29341916
TI  - Effects of surfactant-based permeation enhancers on mannitol permeability,
      histology, and electrogenic ion transport responses in excised rat colonic
      mucosae.
AB  - Surfactant-based intestinal permeation enhancers (PEs) are constituents of
      several oral macromolecule formulations in clinical trials. This study examined
      the interaction of a test panel of surfactant-based PEs with isolated rat colonic
      mucosae mounted in Ussing chambers in an attempt to determine if increases in
      transepithelial permeability can be separated from induction of mucosal
      perturbation. The aim was to assess the effects of PEs on (i) apparent
      permeability coefficient (Papp) of [14C]-mannitol (ii) histology score and (iii)
      short-circuit current (DeltaIsc) responses to a cholinomimetic (carbachol, CCh).
      Enhancement ratio increases for Papp values followed the order: C10 > C9 = C11:1
      > a bile salt blend > sodium choleate > sucrose laurate > Labrasol(r) >C12E8 >
      C12 > Cremophor(r) A25 > C7 > sucrose stearate > Kolliphor(r) HS15 > Kolliphor(r)
      TPGS. Exposures that increased the Papp by >=2-fold over 120 min were accompanied
      by histological damage in 94% of tissues, and by a decreased DeltaIsc response to
      CCh in 83%. A degree of separation between the increased Papp of [14C]-mannitol
      and histological damage and diminution of the DeltaIsc response to CCh was
      observed at selected concentrations of Labrasol(r). Overall, this surfactant
      based PE selection caused transcellular perturbation at similar concentrations to
      those that enhanced permeability.

PMID- 29341917
TI  - A novel method for the production of core-shell microparticles by inverse
      gelation optimized with artificial intelligent tools.
AB  - Numerous studies have been focused on hydrophobic compounds encapsulation as
      oils. In fact, oils can provide numerous health benefits as synergic ingredient
      combined with other hydrophobic active ingredients. However, stable
      microparticles for pharmaceutical purposes are difficult to achieve when commonly
      techniques are used. In this work, sunflower oil was encapsulated in calcium
      alginate capsules by prilling technique in co-axial configuration. Core-shell
      beads were produced by inverse gelation directly at the nozzle using a w/o
      emulsion containing aqueous calcium chloride solution in sunflower oil pumped
      through the inner nozzle while an aqueous alginate solution, coming out from the
      annular nozzle, produced the beads shell. To optimize process parameters
      artificial intelligence tools were proposed to optimize the numerous prilling
      process variables. Homogeneous and spherical microcapsules with narrow size
      distribution and a thin alginate shell were obtained when the parameters as w/o
      constituents, polymer concentrations, flow rates and frequency of vibration were
      optimized by two commercial software, FormRules(r) and INForm(r), which implement
      neurofuzzy logic and Artificial Neural Networks together with genetic algorithms,
      respectively. This technique constitutes an innovative approach for hydrophobic
      compounds microencapsulation.

PMID- 29341918
TI  - Asymmetric flow field flow fractionation for the characterization of globule size
      distribution in complex formulations: A cyclosporine ophthalmic emulsion case.
AB  - Commonly used characterization techniques such as cryogenic-transmission electron
      microscopy (cryo-TEM) and batch-mode dynamic light scattering (DLS) are either
      time consuming or unable to offer high resolution to discern the poly-dispersity
      of complex drug products like cyclosporine ophthalmic emulsions. Here, a size
      based separation and characterization method for globule size distribution using
      an asymmetric flow field flow fractionation (AF4) is reported for comparative
      assessment of cyclosporine ophthalmic emulsion drug products (model formulation)
      with a wide size span and poly-dispersity. Cyclosporine emulsion formulations
      that are qualitatively (Q1) and quantitatively (Q2) the same as Restasis(r) were
      prepared in house with varying manufacturing processes and analyzed using the
      optimized AF4 method. Based on our results, the commercially available
      cyclosporine ophthalmic emulsion has a globule size span from 30 nm to a few
      hundred nanometers with majority smaller than 100 nm. The results with in-house
      formulations demonstrated the sensitivity of AF4 in determining the differences
      in the globule size distribution caused by the changes to the manufacturing
      process. It is concluded that the optimized AF4 is a potential analytical
      technique for comprehensive understanding of the microstructure and assessment of
      complex emulsion drug products with high poly-dispersity.

PMID- 29341919
TI  - Performance of an acoustically mixed pharmaceutical dry powder delivered from a
      novel inhaler.

PMID- 29341920
TI  - Effect of structural factors on release profiles of camptothecin from block
      copolymer conjugates with high load of drug.
AB  - The aim of the present work was the synthesis and study the kinetics and profiles
      of camptothecin (CPT) release form block co- and ter-polymer conjugates
      comprising polylactide (PLA) segments and CPT moieties, structurally diverse by
      degrees of branching, content of d-PLA units and poly(ethylene glycol) methyl
      ether methacrylate (PEGMA). Six PLA, non-toxic macroinitiators (MIs), terminated
      with alpha-bromoester were synthesized. MIs were subjected to polymerization of
      CPT methacrylic derivative (CPTMA) with PEGMA at various ratios. The average
      contents of CPT from elemental analysis, NMR and UV-GPC were approximate to each
      other. The number of CPT molecules and PEGMA units was in the range of 9-195 and
      0-280 per conjugate, respectively. PEGMA units plasticized PLA causing increase
      of its crystallinity, whereas 7% and more of d-PLA caused material amorphous.
      PEGMA units decreased thermal stability of conjugates, however it compatibillized
      the separated phases of PLA and PCPTMA, based on AFM. In vitro release rate of
      CPT from linear PLA conjugates deposited on injection-molded PLA bars increased
      by introduction of PEGMA units with zero-order kinetics and Korsmeyer-Peppas
      model indicating the super case II transport. Branched conjugates revealed some
      burst release and then the release was rather of first-order-kinetics with
      respect to CPT with non-Fickian transport.

PMID- 29341921
TI  - Computational hydrodynamic comparison of a mini vessel and a USP 2 dissolution
      testing system to predict the dynamic operating conditions for similarity of
      dissolution performance.
AB  - The hydrodynamic characteristics of a mini vessel and a USP 2 dissolution testing
      system were obtained and compared to predict the tablet-liquid mass transfer
      coefficient from velocity distributions near the tablet and establish the dynamic
      operating conditions under which dissolution in mini vessels could be conducted
      to generate concentration profiles similar to those in the USP 2. Velocity
      profiles were obtained experimentally using Particle Image Velocimetry (PIV).
      Computational Fluid Dynamics (CFD) was used to predict the velocity distribution
      and strain rate around a model tablet. A CFD-based mass transfer model was also
      developed. When plotted against strain rate, the predicted tablet-liquid mass
      transfer coefficient was found to be independent of the system where it was
      obtained, implying that a tablet would dissolve at the same rate in both systems
      provided that the concentration gradient between the tablet surface and the bulk
      is the same, the tablet surface area per unit liquid volume is identical, and the
      two systems are operated at the appropriate agitation speeds specified in this
      work. The results of this work will help dissolution scientists operate mini
      vessels so as to predict the dissolution profiles in the USP 2, especially during
      the early stages of drug development.

PMID- 29341922
TI  - Sustained release timolol maleate loaded ocusert based on biopolymer composite.
AB  - In the present investigation, the effect of timolol maleate loaded ocuserts was
      studied as an alternative for conventional anti-glaucoma formulation. Ocuserts
      were prepared using natural polymer sodium alginate and ethyl cellulose. Physico
      chemical properties along with drug entrapment efficiency (94-98%), content
      uniformity (93.1% +/- 0.264-98.00% +/- 0.321), in vitro drug release (83.42% +/-
      0.35 at end of 12 h), ex vivo permeation all showed satisfactory results, which
      was found to follow zero order kinetics. Ex vivo permeation studies showed better
      results, revealed that the permeability coefficient was dependent on polymer
      type. The sterility test accelerated stability studies and in vivo studies such
      as eye irritancy test, in vivo drug release of the optimized ocusert was
      determined. The anti-glaucoma activity was measured using Schiotz tonometer at
      different time interval. Significant reduction in Intra ocular pressure (IOP)
      within 3 days was observed in case of rabbits treated with ocusert in comparison
      to the rabbit treated with marketed eye drop formulation. Hence timolol maleate
      loaded ocuserts proved to be a promising and viable alternative over conventional
      eye formulation for the sustained and controlled ophthalmic drug delivery,
      targeting the drug within the ocular globe thus improving patient compliance for
      the treatment of glaucoma.

PMID- 29341923
TI  - Purification, chitooligosaccharide binding properties and thermal stability of
      CIA24, a new PP2-like phloem exudate lectin from ivy gourd (Coccinia indica).
AB  - PP2-like chitin binding phloem exudate lectins, abundant in the sieve tube of
      cucurbits, have been implicated to play key roles in wound sealing and
      antipathogenic responses of the plant. Here we report the affinity purification,
      macromolecular characterization and carbohydrate binding properties of a new
      chitooligosaccharide-specific lectin from the phloem exudate of ivy gourds
      (Coccinia indica). The protein, CIA24, has a subunit mass of 24 kDa. Partial
      sequence analysis indicated that CIA24 exhibits high homology with CIA17 and
      other Cucurbitaceae PP2 proteins whereas CD spectroscopic studies suggested that
      beta-sheets constitute the predominant secondary structure. Temperature dependent
      CD spectroscopic and differential scanning calorimetric studies revealed that
      CIA24 is a highly thermostable protein, which undergoes complete unfolding at
      ~105  degrees C. Isothermal titration calorimetric studies suggested that binding
      of chitooligosaccharides to CIA24 is a highly exothermic process. The lectin
      combining site can accommodate upto a tetrasaccharide with the binding
      stoichiometry (n) close to unity with respect to each protein subunit, whereas
      for chitohexaose a sharp decrease in the binding stoichiometry (n) to ~1:0.5 was
      observed. This suggests that the protein probably undergoes dimerisation in
      presence of chitohexaose, wherein two protein molecules bind to the
      oligosaccharides from the reducing and non-reducing end, respectively.

PMID- 29341924
TI  - Maca polysaccharides: A review of compositions, isolation, therapeutics and
      prospects.
AB  - Maca polysaccharides, some of the major bioactive substances in Lepidium meyenii
      (Walp.) (Maca), have various biological properties, including anti-oxidant, anti
      fatigue, anti-tumor, and immunomodulatory effects, as well as hepatoprotective
      activity and regulation function. Although many therapeutics depend on multiple
      structures of maca polysaccharides in addition to providing sufficient
      foundations for maca polysaccharide products in industrial applications, the
      relationships between the pharmacological effects and structures have not been
      established. Therefore, this article summarizes the extraction and purification
      methods, compositions, pharmacological effects, prospects and industrial
      applications of maca polysaccharides.

PMID- 29341925
TI  - Phase contrast tomography at lab on chip scale by digital holography.
AB  - High-throughput single-cell analysis is a challenging target for implementing
      advanced biomedical applications. An excellent candidate for this aim is label
      free tomographic phase microscopy (TPM). In this paper, some of the methods used
      to obtain TPM are reviewed, analyzing advantages and disadvantages of each of
      them. Moreover, an alternative tomographic technique is described for live cells
      analysis, and future trends of the method are foreseen. In particular, by
      exploiting random rolling of cells while they are flowing along a microfluidic
      channel, it is possible to obtain phase-contrast tomography thus obtaining
      complete retrieval of both 3D-position and orientation of rotating cells. Thus, a
      priori knowledge of such information is no longer needed. This approach extremely
      simplifies the optical system avoiding any mechanical/optical scanning of light
      source. The proof is given for different classes of biosamples, red-blood-cells
      (RBCs) and diatom algae. Accurate characterization of each type of cells is
      reported and compared to that obtained by other tomographic techniques.

PMID- 29341926
TI  - Direct detection of carbon and nitrogen nuclei for high-resolution analysis of
      intrinsically disordered proteins using NMR spectroscopy.
AB  - Nuclear magnetic resonance spectroscopy (NMR) is a powerful technique for
      characterizing the structural and dynamic properties of intrinsically disordered
      proteins and protein regions (IDPs & IDRs). However, the application of NMR to
      IDPs has been limited by poor chemical shift dispersion in two-dimensional (2D)
      1H-15N heteronuclear correlation spectra. Among the various detection schemes
      available for heteronuclear correlation spectroscopy, 13C direct-detection has
      become a mainstay for investigations of IDPs owing to the favorable chemical
      shift dispersion in 2D 13C'-15N correlation spectra. Recent advances in cryoprobe
      technology have enhanced the sensitivity for direct detection of both 13C and 15N
      resonances at high magnetic field strengths, thus prompting the development of
      15N direct-detect experiments to complement established 13C-detection
      experiments. However, the application of 15N-detection has not been widely
      explored for IDPs. Here we compare 1H, 13C, and 15N detection schemes for a
      variety of 2D heteronuclear correlation spectra and evaluate their performance on
      the basis of resolution, chemical shift dispersion, and sensitivity. We performed
      experiments with a variety of disordered systems ranging in size and complexity;
      from a small IDR (99 amino acids), to a large low complexity IDR (185 amino
      acids), and finally a ~73 kDa folded homopentameric protein that also contains
      disordered regions (133 amino acids/monomer). We conclude that, while requiring
      high sample concentration and long acquisition times, 15N-detection often offers
      enhanced resolution over other detection schemes in studies of disordered protein
      regions with low complexity sequences.

PMID- 29341927
TI  - Book lung development in juveniles and adults of the cobweb spider, Parasteatoda
      tepidariorum C. L. Koch, 1841 (Araneomorphae, Theridiidae).
AB  - Light and transmission electron microscopy were used to study the development of
      new book lung lamellae in juvenile and adult spiders (Parasteatoda tepidariorum).
      As hypothesized earlier in a study of embryos, mesenchyme cells dispersed
      throughout the opisthosoma (EMT) are a likely source of precursor epithelial
      cells (MET) for the new lamellae. The precursor cells in juveniles and adults
      continue many of the complex activities observed in embryos, e.g., migration,
      alignment, lumen formation, thinning, elongation, and secretion of the cuticle of
      air channel walls and trabeculae. The apicobasal polarity of precursor cells for
      new channels is apparently induced by the polarity pattern of precursor cells of
      channels produced earlier. Thus, new air and hemolymph channels extend and
      continue the alternating pattern of older channels. At sites more distant from
      the spiracle and atrium, new channels are usually produced by the mode II process
      (intracellular alignment and merging of vesicles). These air channels have
      bridging trabeculae and are quite stable in size throughout their length. At
      sites closer to the spiracle and atrium, new channels may be produced by mode I
      (coalescence of merocrine vesicle secretion). This raises the hypothesis that
      structural and functional differences in mode I and II channels and differing
      oxygen and fluid conditions with distance from the spiracle and atrium determine
      the mode of formation of new channels. Observations herein support an earlier
      hypothesis that there is some intercellular apical/apical and basal/basal
      affinity among the opposed surfaces of aligned precursor cells. This results in
      the alternating pattern of air channels at the apical and hemolymph channels at
      the basal cell surfaces.

PMID- 29341929
TI  - The infection of red seabream iridovirus in mandarin fish (Siniperca chuatsi) and
      the host immune related gene expression profiles.
AB  - Red Sea bream iridovirus (RSIV) was initially isolated from marine fish, which
      belongs to Megalocytivirus, Iridoviridae. It can cause great economic losses in
      fish culture with high morbidity and mortality. In the present study, the
      pathogenicity and immune response associated with a RSIV genotype megalocytivirus
      infection were determined in mandarin fish (Siniperca chuatsi). Fish challenged
      showed typical clinical signs of iridovirus infection, including acute
      haemorrhages and enlarged visceral organs. Histopathological analysis revealed
      that extensive necrosis, vacuolization and inflammation were presented in the
      stomach, spleen, kidney and liver of the diseased fish. Blood cells counting and
      phagocytic assay indicated that the numbers of the red and white blood cells in
      the peripheral blood of infected fish increased significantly compared to the
      control group and the phagocytic percentage of leukocytes peaked at day 6 post
      infection. Quantitive real-time PCR (qRT-PCR) was also undertaken to analyse the
      host defensive response in mandarin fish challenged with RSIV. The expression
      level of ten genes including interferon-related factors (IRFs) IRF1 and IRF7, Mx,
      Viperin, JAK1, STAT1, TCRalpha, TNFalpha, IL-1beta and IL-8 during experimental
      infection were monitored at different point of time in liver, spleen and head
      kidney. Results revealed varying expression profiles and clear transcriptional
      activation of these immune related genes in different tissues, which will
      contribute to better understand the pathogenesis and host defensive system in
      iridovirus invasion.

PMID- 29341930
TI  - Activation of estrogen receptor beta (ERbeta) regulates the expression of N
      cadherin, E-cadherin and beta-catenin in androgen-independent prostate cancer
      cells.
AB  - The aim of the present study was to investigate the impact of the activation of
      estrogen receptors on expression and localization of N-cadherin, E-cadherin and
      non-phosphorylated beta-catenin in androgen-independent prostate cancer cells (PC
      3 and DU-145) and in human post pubertal prostate epithelial cells (PNT1A).
      Expression of N-cadherin was detected in PNT1A and PC-3 cells, but not in DU-145
      cells. E-cadherin was detected only in DU-145 cells and beta-catenin was detected
      in all cells studied. N-cadherin and beta-catenin were located preferentially in
      the cellular membrane of PNT1A cells and in the cytoplasm of PC-3 cells. E
      cadherin and beta-catenin were located preferentially in the cellular membrane of
      DU-145 cells. 17beta-estradiol (E2) or the ERalpha-selective agonist PPT did not
      affect the content and localization of N-cadherin in PC-3 and PNT1A cells or E
      cadherin in DU-145 cells. In PC-3 cells, ERbeta-selective agonist DPN decreased
      the expression of N-cadherin. DPN-induced downregulation of N-cadherin was
      blocked by pretreatment with the ERbeta-selective antagonist (PHTPP), indicating
      that ERbeta1 is the upstream receptor regulating the expression of N-cadherin. In
      DU-145 cells, the activation of ERbeta1 by DPN increased the expression of E
      cadherin. Taken together, these results suggest that activation of ERbeta1 is
      required to maintain an epithelial phenotype in PC-3 and DU-145 cells. The
      activation of ERbeta1 also increased the expression of beta-catenin in cytoplasm
      of PC-3 and in the cellular membrane of DU-145 cells. In conclusion, our results
      indicate differential expression and localization of N-cadherin, E-cadherin and
      beta-catenin in androgen-independent prostate cancer cells. The reduction of N
      cadherin content by activation of ERbeta, exclusively observed in androgen
      independent prostate cancer cells (PC-3), may be related to the activation of
      signaling pathways, such as the release of beta-catenin into the cytoplasm,
      translocation of beta-catenin to the nucleus and activation of gene
      transcription.

PMID- 29341928
TI  - A novel brown adipocyte-enriched long non-coding RNA that is required for brown
      adipocyte differentiation and sufficient to drive thermogenic gene program in
      white adipocytes.
AB  - The thermogenic activities of brown and beige adipocytes can be exploited to
      reduce energy surplus and counteract obesity. Recent RNA sequencing studies have
      uncovered a number of long noncoding RNAs (lncRNAs) uniquely expressed in white
      and brown adipose tissues (WAT and BAT), but whether and how these lncRNAs
      function in adipogenesis remain largely unknown. Here, we report the
      identification of a novel brown adipocyte-enriched LncRNA (AK079912), and its
      nuclear localization, function and regulation. The expression of AK079912
      increases during brown preadipocyte differentiation and in response to cold
      stimulated browning of white adipocytes. Knockdown of AK079912 inhibits brown
      preadipocyte differentiation, manifested by reductions in lipid accumulation and
      down-regulation of adipogenic and BAT-specific genes. Conversely, ectopic
      expression of AK079912 in white preadipocytes up-regulates the expression of
      genes involved in thermogenesis. Mechanistically, inhibition of AK079912 reduces
      mitochondrial copy number and protein levels of mitochondria electron transport
      chain (ETC) complexes, whereas AK079912 overexpression increases the levels of
      ETC proteins. Lastly, reporter and pharmacological assays identify Ppargamma as
      an upstream regulator of AK079912. These results provide new insights into the
      function of non-coding RNAs in brown adipogenesis and regulating browning of
      white adipocytes.

PMID- 29341931
TI  - Bioinspired capsules based on nanocellulose, xyloglucan and pectin - The
      influence of capsule wall composition on permeability properties.
AB  - : Materials based on renewable biopolymers, selective permeability and stimuli
      responsive release/loading properties play an important role in biomedical
      applications. Here, in order to mimic the plant primary cell-wall, microcapsules
      have been fabricated using cell wall polysaccharides, namely pectin, xyloglucan
      and cellulose nanofibers. For the first time, a large amount of xyloglucan was
      successfully included in such capsules. These capsules demonstrated stimuli
      responsive (ON/OFF) permeability and biocompatibility. The live cell staining
      revealed that the microcapsules' surface enhanced cell growth and also the non
      toxic nature of the microcapsules. In water, the microcapsules were completely
      and partially permeable to fluorescent dextrans with an average molecular weight
      of 70 kDa (hydrodynamic diameter of ca. 12 nm) and 2000 kDa (ca. 54 nm),
      respectively. On the other hand, the permeability dropped quickly when the
      capsules were exposed to 250 mM NaCl solution, trapping a fraction of the 70 kDa
      dextrans in the capsule interior. The decrease in permeability was a direct
      consequence of the capsule-wall composition, i.e. the presence of xyloglucan and
      a low amount of charged molecules such as pectin. The low permeability of
      capsules in saline conditions (and in a model biological medium), combined with a
      capsule wall that is made from dietary fibers only, potentially enables their use
      in biological applications, such as colon targeted delivery in the gastro
      intestinal tract. STATEMENT OF SIGNIFICANCE: For the first time, microcapsules
      have been prepared that possess capsule walls that mimic the primary cell wall
      found in natural plant cells. The capsules were assembled using pectin,
      xyloglucan and cellulose in the form of cellulose nanofibers. The capsules
      demonstrated stimuli-responsive (ON/OFF) permeability and biocompatibility. The
      low permeability of capsules in saline conditions (and in a model biological
      medium), combined with a capsule wall that is made from dietary fibers only,
      potentially enables their use in biological applications, such as colon targeted
      delivery in the gastro-intestinal tract. Such model plant cell capsules might
      also further improve the understanding for the digestion and release of nutrients
      from natural plant cells found in vegetables and fruits.

PMID- 29341932
TI  - Synthetic extracellular matrix mimic hydrogel improves efficacy of mesenchymal
      stromal cell therapy for ischemic cardiomyopathy.
AB  - BACKGROUND: Mesenchymal stromal cells (MSC) repair infarcted hearts mainly
      through paracrine mechanisms. Low cell engraftment limits the release of soluble
      paracrine factors (SF) over time and, consequently, MSC efficacy. We tested
      whether a synthetic extracellular matrix mimic, a hydrogel containing heparin (H
      HG), could ameliorate MSC engraftment and binding/release of SF, thus improving
      MSC therapy efficacy. METHODS AND RESULTS: In vitro, rat bone-marrow MSC (rBM
      MSC) were seeded and grown into H-HG. Under normoxia, the hydrogel did not affect
      cell survival (rBM-MSC survival >90% at each time point tested); vice versa,
      under hypoxia the biomaterial resulted to be protective for the cells (p < .001
      vs rBM-MSC alone). H-HG or control PEG hydrogels (HG) were incubated with VEGF or
      bFGF for binding/release quantification. Data showed significantly higher amount
      of VEGF and bFGF bound by H-HG compared with HG (p < .05) and a constant release
      over time. In vivo, myocardial infarction (MI) was induced in female Sprague
      Dawley rats by permanent coronary ligation. One week later, saline, rBM-MSC, H-HG
      or rBM-MSC/H-HG were injected in the infarct zone. The co-injection of rBM-MSC/H
      HG into infarcted hearts significantly increased cardiac function. Importantly,
      we observed a significant gain in MSC engraftment, reduction of ventricular
      remodeling and stimulation of neo-vasculogenesis. We also documented higher
      amounts of several pro-angiogenic factors in hearts treated with rBM-MSC/H-HG.
      CONCLUSIONS: Our data show that H-HG increases MSC engraftment, efficiently fine
      tunes the paracrine MSC actions and improves cardiac function in infarcted rat
      hearts. STATEMENT OF SIGNIFICANCE: Transplantation of MSC is a promising
      treatment for ischemic heart disease, but low cell engraftment has so far limited
      its efficacy. The enzymatically degradable H-HG that we developed is able to
      increase MSC retention/engraftment and, at the same time, to fine-tune the
      paracrine effects mediated by the cells. Most importantly, the co-transplantation
      of MSC and H-HG in a rat model of ischemic cardiomyopathy improved heart function
      through a significant reduction in ventricular remodeling/scarring and
      amelioration in neo-vasculogenesis/endogenous cardiac regeneration. These
      beneficial effects are comparable to those obtained by others using a much
      greater number of cells, strengthening the efficacy of the biomaterial used in
      increasing the therapeutic effects of MSC. Given its efficacy and safety,
      documented by the absence of immunoreaction, our strategy appears readily
      translatable to clinical scenarios.

PMID- 29341933
TI  - The effects of platelet lysate patches on the activity of tendon-derived cells.
AB  - : Platelet-derived biomaterials are widely explored as cost-effective sources of
      therapeutic factors, holding a strong potential for endogenous regenerative
      medicine. Particularly for tendon repair, treatment approaches that shift the
      injury environment are explored to accelerate tendon regeneration. Herein,
      genipin-crosslinked platelet lysate (PL) patches are proposed for the delivery of
      human-derived therapeutic factors in patch augmentation strategies aiming at
      tendon repair. Developed PL patches exhibited a controlled release profile of PL
      proteins, including bFGF and PDGF-BB. Additionally, PL patches exhibited an
      antibacterial effect by preventing the adhesion, proliferation and biofilm
      formation by S. aureus, a common pathogen in orthopaedic surgical site
      infections. Furthermore, these patches supported the activity of human tendon
      derived cells (hTDCs). Cells were able to proliferate over time and an up
      regulation of tenogenic genes (SCX, COL1A1 and TNC) was observed, suggesting that
      PL patches may modify the behavior of hTDCs. Accordingly, hTDCs deposited tendon
      related extracellular matrix proteins, namely collagen type I and tenascin C. In
      summary, PL patches can act as a reservoir of biomolecules derived from PL and
      support the activity of native tendon cells, being proposed as bioinstructive
      patches for tendon regeneration. STATEMENT OF SIGNIFICANCE: Platelet-derived
      biomaterials hold great interest for the delivery of therapeutic factors for
      applications in endogenous regenerative medicine. In the particular case of
      tendon repair, patch augmentation strategies aiming at shifting the injury
      environment are explored to improve tendon regeneration. In this study, PL
      patches were developed with remarkable features, including the controlled release
      of growth factors and antibacterial efficacy. Remarkably, PL patches supported
      the activity of native tendon cells by up-regulating tenogenic genes and enabling
      the deposition of ECM proteins. This patch holds great potential towards
      simultaneously reducing post-implantation surgical site infections and promoting
      tendon regeneration for prospective in vivo applications.

PMID- 29341934
TI  - Advances in the delivery of antisense oligonucleotides for combating bacterial
      infectious diseases.
AB  - Discovery and development of new antibacterial drugs against multidrug resistant
      bacterial strains have become more and more urgent. Antisense oligonucleotides
      (ASOs) show immense potential to control the spread of resistant microbes due to
      its high specificity of action, little risk to human gene expression, and easy
      design and synthesis to target any possible gene. However, efficient delivery of
      ASOs to their action sites with enough concentration remains a major obstacle,
      which greatly hampers their clinical application. In this study, we reviewed
      current progress on delivery strategies of ASOs into bacteria, focused on various
      non-virus gene vectors, including cell penetrating peptides, lipid nanoparticles,
      bolaamphiphile-based nanoparticles, DNA nanostructures and Vitamin B12. The
      current review provided comprehensive understanding and novel perspective for the
      future application of ASOs in combating bacterial infections.

PMID- 29341935
TI  - Systemic Sclerosis: Small mouth, big burden?

PMID- 29341936
TI  - Rheumatic manifestations among cancer patients treated with immune checkpoint
      inhibitors.
AB  - BACKGROUND: The use of immune checkpoint inhibitors (ICI) has grown incessantly
      since they were first approved in 2014. These monoclonal antibodies inhibit T
      cell activation, yielding a dramatic tumor response with improved survival.
      However, immunotherapy is frequently hampered by immune adverse events (iAE) such
      as hypophysitis, colitis, hepatitis, pneumonitis and rash. Until recently,
      rheumatic side effects were only infrequently reported. AIM: To describe the
      rheumatic manifestations encountered among patients treated with ICIs in a large
      tertiary cancer center in Israel METHODS: The cancer center's patient registry
      was screened for patients who had ever been treated with ipilimumab,
      pembrolizumab and/or nivolumab with relevant data gathered from clinical charts.
      RESULTS: Rheumatic manifestations were encountered in 14 of 400 patients (3.5%)
      who had received immunotherapy between January 1st 2013 and April 30th, 2017. The
      most common rheumatic manifestation was inflammatory arthritis (85%) for which a
      third (4/11) had a clear cut predisposing factor such as a personal or family
      history of psoriasis, a prior episode of uveitis or ACPA positivity. Pulmonary
      sarcoidosis and biopsy-proven eosinophilic fasciitis were diagnosed in two
      additional patients. Treatment with NSAIDS was mostly unsuccessful while steroid
      therapy was beneficial in doses >=20 mg/d. Methotrexate enabled steroid tapering
      without an excess of side effects or tumor progression in the short follow-up
      available. Overall, rheumatic manifestations tended to occur later in the course
      of immunotherapy as compared to other iAE. CONCLUSIONS: Our findings underscore
      that rheumatic iAE are part of the side effect profile of ICIs and require
      heightened awareness as these therapies are becoming the standard of care for
      various malignancies. We show that these appear later in the course of iAEs and
      respond preferentially to high dose steroids. MTX appears effective as a steroid
      sparing agent.

PMID- 29341937
TI  - Correction for: Opening the Black Box of Electronic Health: Collecting,
      Analyzing, and Interpreting Log Data.
AB  - [This corrects the article DOI: .].

PMID- 29341938
TI  - Increased serum concentrations of soluble ST2 are associated with pulmonary
      complications and mortality in polytraumatized patients.
AB  - BACKGROUND: We sought to evaluate the role of soluble ST2 (suppression of
      tumorigenicity) serum concentrations in polytraumatized patients and its
      potential role as biomarker for pulmonary complications. METHODS: We included
      severely injured patients (injury severity score>=16) admitted to our level I
      trauma center and analyzed serum samples obtained on the day of admission and on
      day 2. Furthermore, patients with isolated thoracic injury and healthy probands
      were included and served as control groups. Serum samples were analyzed for
      soluble ST2 concentrations with a commercially available ELISA kit. RESULTS: A
      total of 130 patients were included in the present study. Five patients with
      isolated thoracic injury and eight healthy probands were further included. Serum
      analyses revealed significantly elevated concentrations of soluble ST2 in
      polytraumatized patients compared to patients suffering from isolated thoracic
      trauma and healthy probands. In polytraumatized patients who developed pulmonary
      complications (acute respiratory distress syndrome and pneumonia) and in patients
      who died, significantly higher serum concentrations of soluble ST2 were found on
      day 2 (p<0.001). Serum concentrations of soluble ST2 on day 2 were of prognostic
      value to predict pulmonary complications in polytraumatized patients (area under
      the curve=0.720, 95% confidence interval=0.623-0.816). Concomitant thoracic
      trauma had no further impact on serum concentrations of soluble ST2. CONCLUSIONS:
      Serum concentrations of soluble ST2 are upregulated following polytrauma.
      Increased concentrations were associated with worse outcome.

PMID- 29341939
TI  - The quest for equivalence of test results: the pilgrimage of the Dutch
      Calibration 2.000 program for metrological traceability.

PMID- 29341940
TI  - Mucocele of the Sphenoid Sinus.
AB  - Mucocele of the paranasal sinuses is a rare disease with slow evolution. It is a
      benign, encapsulated and destructive formation filled with mucous fluid and
      tapistrated with respiratory epithelium. Of all the paranasal sinuses, the
      sphenoid sinus is affected in only 1-7% of the cases. We present two cases of
      mucocele of the sphenoid sinus involving the posterior ethmoidal cells. We
      consider here their clinical presentation, use of neuroimaging in the diagnosis,
      surgical care and postoperative results. Both patients presented with a history
      of persistent headache and in addition, one of them had a paresis of the right
      oculomotor and abducens nerves. A transnasal endoscopic sphenoidectomy was
      performed in both patients, in one - with an evacuation of the mucocele and
      marsupialization, and in the other - with a balloon dilatation of the natural
      foramen of the sinus. Postoperatively, a complete reversal of the symptoms was
      observed in both patients. Mucocele of the paranasal sinuses should be considered
      as a diagnosis in cases of persistent headache with a primarily retrobulbar
      location and eye symptoms. Computed tomography and magnetic resonance imaging can
      be used to successfully diagnose the disease. The transnasal endoscopic
      sphenoidectomy is the therapeutic method of choice which allows evacuation of the
      mucocele, while the marsupialization allows good drainage and prevents
      recurrence.

PMID- 29341941
TI  - Cauda Equina Syndrome Due to Lumbar Disc Herniation: a Review of Literature.
AB  - Cauda equina syndrome (CES) is a rare neurologic condition that is caused by
      compression of the cauda equina. Cauda equina consists of spinal nerves L2-L5, S1
      S5 and the coccygeal nerve. The compression of these nerve roots can be caused
      mainly by lumbar disc herniation (45% of all causes). The diagnosis consists of
      two critical points: a) detailed history and physical examination and b) MRI or
      CT. The gold standard of the treatment of this syndrome is the surgical approach
      in combination with the timing of onset of symptoms. The surgery as an emergency
      situation is recommended in the fi rst 48 hours of onset of symptoms. Any delay
      in diagnosis and treatment leads to a poor prognosis of CES.

PMID- 29341942
TI  - Enteritis-associated Acute Febrile Neutrophilic Dermatosis with Acute
      Monoarthritis.
AB  - Febrile neutrofilic dermatosis is an uncommon entity with complex
      pathophysiology, usually secondary to an infection, a malignancy or an autoimmune
      disease. Extracutaneous manifestations of the disease are very rare as well. We
      report a patient with histologically confirmed acute febrile neutrophilic
      dermatosis caused by viral enteritis that was presented with painful rash along
      with acute monoarthritis and treated with oral corticosteroids.

PMID- 29341943
TI  - Beneficial Effect of Chronic Treatment with Extracts from Rhodiola Rosea L. and
      Curcuma Longa L. on the Immunoreactivity of Animals Subjected to a Chronic Mild
      Stress Model.
AB  - BACKGROUND: Recent studies have suggested increased levels of pro-inflammatory
      cytokines in depression. AIM: The present study aimed to evaluate the effect of
      extracts from Rhodiola and Curcuma on immunoreactivity of animals subjected to a
      chronic mild stress (CMS) model followed by lipopolysaccharide-induced
      inflammation. MATERIALS AND METHODS: Male Wistar rats (n=56) divided in 7 groups
      were treated orally with: distilled water 10 ml/kg (control and CMS model
      groups); Rhodiola 250 mg/kg; Rhodiola 500 mg/kg; Curcuma 250 mg/kg; Curcuma 500
      mg/kg, Rhodiola 250 mg/kg and Curcuma 250 mg/kg. All groups except the control
      were stressed daily according to a CMS protocol. Changes in glucose preference,
      weight gain and locomotor activity were recorded. In the sixth week the animals
      were challenged with LPS and rats' sera were obtained for ELISA evaluation of TNF
      alpha and IL-6 levels. RESULTS: The animals from the model group decreased their
      weight gain, glucose preference and locomotor activity compared to controls. The
      groups exposed to stress and treated with Rhodiola 500 mg/kg, Curcuma 500 mg/kg
      and their combination increased their locomotor activity compared to the model
      group. High expression of the pro-inflammatory cytokines TNF-alpha and IL-6 were
      found in all groups exposed to CMS and challenged by LPS. CONCLUSIONS: The groups
      exposed to the stress procedure showed a variety of depression-like behavioral
      changes. In addition, ELISA tests showed that CMS is affecting rats' immunity by
      increasing the cytokines' levels. These changes could be reversed by
      administration of Rhodiola and Curcuma in combination suggesting synergic
      interaction regarding their anti-inflammatory and anti-stress effects.

PMID- 29341944
TI  - Nuclear Medicine Methods for Evaluation of Abnormal Parathyroid Glands in
      Patients with Primary and Secondary Hyperparathyroidism.
AB  - Considered rare disease in the past, primary hyperparathyroidism (PHPT) has
      dramatically increased in incidence over the past thirty years with the
      introduction of routine calcium measurements; it is now approximately 42 per 100
      000 persons. By far, the most common lesion found in patients with PHPT is the
      solitary parathyroid adenoma, occurring in 85%-90% of patients, while in the rest
      10%- 15% primary hyperplasia of the parathyroid glands is present. Currently, the
      most widely used surgical approach is minimally invasive parathyroidectomy which
      is associated with less post-surgery complications and shorter operation time. To
      be successful this procedure needs to rely on a precise preoperative localization
      of the abnormal parathyroid glands, hence preoperative parathyroid imaging gained
      so large importance. The rationale for locating abnormal parathyroid tissue prior
      to surgery is that the glands can be notoriously unpredictable in their location.
      There is a general consensus that the best imaging procedure identifying abnormal
      parathyroid glands is the preoperative scintigraphy with 99mTc-sestamibi or 99mTc
      tetrofosmin. It is characterized with high sensitivity and specificity exceeding
      those of ultrasound, CT or MRI. Combining scintigraphy with the other imaging
      techniques increases the precision for topic localization.

PMID- 29341945
TI  - Lessons about Causes and Management of an Ebola Outbreak.
AB  - Ebola virus disease (EVD) is one of the deadliest viral diseases. It is
      characterized by a high mortality rate due to the lack of effective and safe
      treatments or vaccines and its ability to spread at an unstoppable pace. The West
      Africa outbreak ended but the disease may strike again at any time. The latest
      epidemic was, by far, the deadliest to date. The most concern was why this
      outbreak was so different from the previous ones. We proposed in this review
      firstly to summarize the principal causes of its unprecedented spread and
      secondly to identify the steps for an effective management approach of a future
      Ebola outbreak. Attributes of the affected populations and insufficient control
      efforts were the main reasons of its amplification. This was complicated by a
      delayed international response. The health crisis was ignored for months until it
      got out of control. The management of Ebola presents a multitude of challenges in
      terms of preparedness and capacity to face an outbreak. In addition to the need
      for adequate health care facilities, ongoing surveillance tools, appropriate
      training of health workers and raising population awareness, readiness requires a
      large scale and coordinated international intervention to support affected and at
      risk nations, to intensify their response activities and to strengthen their
      capacities. Constant interventions after the outbreak are still needed to ensure
      that vital health and related service institutions in these countries are fully
      prepared to respond to an eminent epidemic.

PMID- 29341946
TI  - Microemulgel of Voriconazole: an Unfathomable Protection to Counter Fungal
      Contagiousness.
AB  - BACKGROUND: Fluconazole and ketoconazole both have poor minimum inhibitory
      concentration than voriconazole. Voriconazole had serious side effects in oral
      and intravenous doses. It has poor water solubility. The objective of the study
      was to prepare and optimize microemulgel of voriconazole for topical delivery.
      AIM: Formulation, development, and evaluation of voriconazole microemulgel for
      topical delivery. METHODS: Oil and emulsifi ers selected were on the basis of
      equilibrium solubility study and emulsification property respectively. The pseudo
      ternary plot and constrained simplex lattice design were applied for preparation
      of microemulsions. Microemulsions were subjected to micelle size, zeta potential,
      polydispersity index, and in vitro study. They were optimized by Design-Expert(r)
      9.0.3.1 software. Formulation, development, evaluation and optimization of
      microemulgel were carried out. Microbial assay of an optimized batch of
      microemulgel was performed. RESULTS: Solubility of voriconazole in Parker Neem(r)
      oil was 7.51+/-0.14 mg/g. AcrysolTMK-150: PEG-400 in 4:1 ratio had the highest
      area for microemulsion. 59.2% AcrysolTMK-150, 14.8% PEG-400, 11% Parker Neem(r)
      oil, 15% rose water, and 1% voriconazole as an optimized batch of microemulsion
      was selected for preparation of microemulgel. Carbomer 934P found a good gelling
      agent in 0-2% w/w concentration. An optimized batch of microemulgel had 0.974
      desirability value. An optimized batch of microemulgel and Nizral(r) cream had
      37.32+/-0.63% and 26.45+/-0.63% zones of inhibition. CONCLUSION: Topical
      antifungal treatment was successfully achieved with voriconazole microemulgel.

PMID- 29341947
TI  - Spontaneous Direct Carotid-Cavernous Fistula in an Elderly Patient.
AB  - We describe the case of an 83-year-old woman with left-sided ophthalmoplegia. She
      had no family history of connective tissue disease. The computed tomography study
      found a dilated left cavernous sinus. The conventional cerebral panangiography
      confirmed the diagnosis - a direct carotid-cavernous fistula (CCF), with no
      evidence of ruptured aneurysm. The woman underwent endovascular treatment with
      coiling of the cavernous sinus in combination with application of the Onyx
      embolic agent in the fistula. During the first 48 hours after the embolization
      the local pain, exophthalmos and conjunctival injection of the left eye were
      significantly ameliorated. The pulsatile tinnitus on the left disappeared and the
      ptosis of the left eyelid partially recovered. Selective angiography is the best
      method for the diagnosis and classification of CCF. Currently, treatment is
      possible with low mortality and morbidity rates. The endovascular intervention is
      able to completely occlude the fistula and maintain adequate blood fl ow through
      the carotid artery.

PMID- 29341948
TI  - Biochemical Changes in Experimental Rat Model of Abdominal Compartment Syndrome.
AB  - BACKGROUND: Increased intra-abdominal pressure (IAP) causes tissue ischemia,
      subsequent hypoxia, and impairment of normal tissue metabolism. Elevation of IAP
      above 20 mmHg leads to progression of abdominal compartment syndrome (ACS) that
      is associated with organ dysfunction or failure not previously manifested. AIM:
      To evaluate the eff ects of diff erent grades and time of exposure to IAP on
      biochemical parameters and oxidative stress in organs aff ected by ischemia using
      previously developed rat model. RESULTS: Three experimental groups exposed to
      diff erent IAP and time frames were tested for liver, kidney, and pancreas injury
      by measuring the activities of tissue specifi c enzymes in blood serum. Elevated
      activities of aspartate aminotransferase, pancreatic amylase, lipase, and higher
      concentrations of D-lactate, urea, and creatinine were found in some of the
      experimental groups compared to a control group of animals not subjected to
      increased IAP. Increased levels of biomarkers of oxidative stress as well as
      decrease in concentration of the major cellular antioxidant glutathione indicated
      the presence of oxidative injury as a result of elevated IAP. CONCLUSIONS: The
      developed rat model is appropriate to study the mechanism and manifestation of
      tissue injury during diff erent grades of elevated IAP but also to test
      approaches aimed to attenuate the detrimental eff ects of ACS. This study also
      underlines the necessity of using not a single but a set of biochemical
      parameters in order to assess the severity of tissue injury during elevated IAP
      and progression to ACS.

PMID- 29341949
TI  - Impact of Air Pollution and Outdoor Temperature on the Rate of Chronic
      Obstructive Pulmonary Disease Exacerbations.
AB  - BACKGROUND: Environmental pollution can be one of the main risk factors for acute
      exacerbations of chronic obstructive pulmonary disease (COPD). AIM: To study the
      relationship between air pollution, outdoor temperature and exacerbations of
      COPD. MATERIALS AND METHODS: COPD patients (n=1432) were followed up for one
      year. The levels of particulate matter up to 10 MUm (PM10), nitrogen dioxide
      (NO2), sulfur dioxide (SO2) and outside temperatures were collected from the
      Environmental Agency database. RESULTS: A total of 309 acute COPD exacerbations
      (AECOPD) were recorded in the analysis. The daily mean concentrations of PM10
      were found to correlate significantly with the daily mean concentrations of NO2
      and SO2 (rho 0.34 and rho 0.49, respectively; p=0.0001). The negative
      correlations between the daily mean temperature and the daily mean levels of
      PM10, NO2 and SO2 were also significant (rho -0.44, rho -0.11, and rho -0.37,
      respectively; p=0.0001). The daily number of AECOPD correlated with the mean
      levels of PM10 in the previous six days (rho 0.14; p=0.02) and the lower outdoor
      temperature (rho -0.2; p=0.001). The negative correlation between the daily
      number of AECOPD and the mean daily temperature was stronger in days with levels
      of PM10 above 50 MUg/m3 (rho -0.3 p=0.02 vs. rho -0.18 p= 0.01). CONCLUSION:
      Lower daily mean temperatures were associated with the levels of air pollutants.
      The level of PM10 correlated with the levels of the other air pollutants. The
      daily number of AECOPD was found to correlate weakly, but signifi cantly with the
      mean level of PM10 in the previous six days.

PMID- 29341950
TI  - Clinical Characteristics of Ulceroglandular Tularemia in Two Bulgarian Regions,
      2014-2015: a Report of Five Cases.
AB  - We present here the first five human cases with tularemia from two regions in
      South Bulgaria in which there had been no previous report of the infection. The
      cases occurred over a period of 8 months (December 2014 - August 2015). They were
      treated at the Department of Infectious Diseases in Stara Zagora University
      Hospital, Bulgaria. We present the clinical, epidemiological and laboratory data
      for four men and one woman (age range 52 to 73 years). Three men were hunters,
      four patients took part in handling, preparing/skinning and cooking the game
      animals. One man marked agricultural work and contact with straw stems. After a
      mean incubation period of 4.8+/-1.4 days ulcers appeared, followed by local
      painful lymphadenitis. All patients presented with liver enlargement and
      elevation in acute phase reactants. The etiological diagnosis was made by tube
      agglutination test in all cases, PCR positive result was found in one. The
      administered antibacterial treatment was a combination of aminoglycosides and 4
      quinolones with the outcome being favorable for all patients. The current report
      suggests presence of Francisella tularensis in South Bulgaria.

PMID- 29341951
TI  - Spermicidal Constituents of Ethanolic Extract of Sacoglottis gabonensis Stem
      Bark.
AB  - AIM: To isolate the spermicidal constituents of Sacoglottis gabonensis. MATERIALS
      AND METHODS: The ethanolic extract with partitioned fractions of Sacoglottis
      gabonensis stem bark were subjected to sperm immobilization assay. The most
      active EtOAc fraction was further purifi ed by column and Semi-Preparative High
      Performance Liquid Chromatography to give compounds which were characterized by
      spectroscopic methods (UV, LC/MS, and NMR). The compound(s) was also tested for
      sperm immobilization activity. RESULTS: The ethanolic extract showed 100% signifi
      cant (p < 0.05) sperm immobilization activity at a concentration of 30 mg/mL at
      20 s compared to both negative and positive controls. The most active ethyl
      acetate fraction yielded methyl 3,5-dihydroxy-4-methoxybenzoate, eriodictyol and
      bergenin. Bergenin had 100% sperm immobilization activity at 20 mg/mL in 60 s
      which was signifi cant (p < 0.05) also when compared to the positive and negative
      control while methyl 3,5-dihydroxy- 4-methoxybenzoate, eriodictyol were not
      active. CONCLUSION: The active spermicidal constituent in Sacoglottis gabonensis
      stem bark extract is bergenin. However, methyl 3,5-dihydroxy-4-methoxybenzoate
      and eriodictyol showed no activity. This plant is known for its aphrodisiac
      action; hence, caution may have to be exercised in its use because of its
      spermicidal eff ect.

PMID- 29341952
TI  - A Pharmacological Review: Leptadenia reticulata (Wight & Arn.); Jivanti: the Real
      Life Giving Plant.
AB  - The present review reveals a comprehensive description of various pharmacological
      studies carried out on Leptadenia reticulata, a source of several active
      compounds, i.e. Leptadenia reticulata plant belonging to family Asclepiadaceae,
      it is also known as 'Jivanti', used for the treatment of various ailments in
      human civilization as well as used in folk medicine as a remedy in various
      reported herbal formulations. The plant has been found to exhibit diverse
      pharmacological activities like antibacterial activity, anticancer activity,
      lactogenic eff ect, antioxidant activity, anti-implantation activity, anti
      asthmatic activity, modulating eff ect, activity of silver nano particles,
      hepatoprotective activity, antifungal activity, antidiabetic activity and anti
      infl ammatory activity. Traditionally, the plant promotes fi tness and vigor, the
      tone of voice, cures eye diseases, fever, and night blindness, cough, maintain
      pregnancy and gangrene. In this review, we give the recent scientifi c update on
      this plant with therapeutic potential and discuss the methods of carrying out
      studies. The present review draws the attention of researchers towards the
      potential therapeutic activity of Leptadenia reticulata for their active
      constitute.

PMID- 29341953
TI  - Lethality among Patients with HIV/AIDS Monitored in the Clinic of Infectious
      Diseases in St George University Hospital, Plovdiv, 2010-2014.
AB  - BACKGROUND: The introduction of complex antiretroviral therapy has resulted in
      signifi cant decrease in the mortality rate of HIV positive patients, but it
      still remains unacceptably high, especially in some groups of patients. AIM: To
      investigate the death rate in patients with HIV/AIDS, lethality and mortality in
      co-infection, and the most common causes and predictors of fatal outcome, focused
      on early diagnosis and appropriate therapy. MATERIALS AND METHODS: The study
      included 53 deceased patients with HIV/AIDS, monitored at the Clinic of
      Infectious Diseases in St George University Hospital, Plovdiv between 01.01.2010
      and 31.12.2014. The methods of research included clinical analysis, laboratory
      tests, microbiological and serological tests (HCV, HBV, toxoplasmosis), ELISA,
      PCR. Statistical analysis was performed by descriptive statistics, the Student's
      t-test, the method of Van der Ward, and regression analysis (logistic
      regression). RESULTS: During the study period 316 patients with HIV/AIDS were
      monitored, 53 of them with lethal outcome. Lethality was 16.7% for the whole
      group; in intravenous drug users - 13.8%; in co-infected patients: HIV/M.
      tuberculosis - 46%, in HIV/HCV - 17.8%. Lethality and mortality in HIV(+)
      patients with co-infections in populations of diff erent age, gender, duration
      since starting sART and degree of immunodefi ciency (according to CD4, VL) was
      compared with the lethality and mortality in patients with these conditions from
      the general population. CONCLUSIONS: Fatal outcome in patients with HIV/AIDS was
      most commonly associated with co-infections HIV/M. tuberculosis and HIV/HCV.
      Predictors of a fatal outcome are pulmonary tuberculosis, advanced immunodefi
      ciency with VL> 500 000 c/MUL and CD4 <100/mm3, absence or non-systemic
      antiretroviral therapy.

PMID- 29341954
TI  - Carbapenemase Production of Clinical Isolates Acinetobacter baumannii and
      Pseudomonas aeruginosa from a Bulgarian University Hospital.
AB  - BACKGROUND: Production of Bla OXA-23, OXA-24, OXA-58 and hyperexpression of OXA
      51 due to ISAba1 insertion sequence are the leading causes of carbapenem
      resistance in Acinetobacter baumannii. The loss of OprD transmembrane protein and
      the overexpression of some effl ux pumps are considered to be the main factors
      for carbapenem resistance in Pseudomonas aeruginosa whereas metallo-enzymes'
      production has a secondary role. AIM: To examine the carbapenem resistance due to
      carbapenemase production among clinically signifi cant Gram-negative non
      fermenters from St George University hospital, Plovdiv: A. baumannii and P.
      aeruginosa. MATERIALS AND METHODS: Forty three A. baumannii and 43 P. aeruginosa
      isolates, resistant or with intermediate resistance to imipenem and/or meropenem
      were included in the study. They were collected from patients admitted in 14
      various hospital wards between 2010 and 2014. Both phenotypic and genetic methods
      were used for identifi cation and antimicrobial susceptibility testing. RESULTS:
      All A. baumannii demonstrated carbapenemase production determined by a modifi ed
      Hodge test whereas P. aeruginosa isolates did not show this phenomenon. OXA-23
      genes were determined in 97.7% (42 out of 43) of A. baumannii isolates
      indistinguishable from the sequence of the classical ARI-1 gene. OXA-24, OXA-58
      and overexpression of OXA-51 were not registered in any of the isolates. All P.
      aeruginosa were negative for blaVIM and blaIMP genes. CONCLUSION: The leading
      cause of carbapenem resistance in A. baumannii isolates from our hospital is the
      carbapenemase production due to the expression of OXA- 23 gene, whereas in P.
      aeruginosa - the loss of transmembrane OprD protein and the effl ux pumps'
      hyperexpression are suspected to be the main mechanisms.

PMID- 29341955
TI  - Emergency medicine residency programs: the changing face of graduate medical
      education.

PMID- 29341956
TI  - Microbiome associated with denture malodour.
AB  - In the past, our inability to cultivate most of the oral microorganisms has
      limited our view of this complex ecosystem. In the present study, we utilized
      next generation deep sequencing techniques to revisit the microbiome associated
      with denture malodour, a growing field with the rise in life expectancy. The
      study population comprised 26 full dentures patients (mean age 71 +/- 6.4, 10
      males, 16 females) who visited the Tel Aviv University dental geriatric clinic.
      Denture malodour was rated organoleptically by a single odour judge, and dentures
      scoring 2 and above were considered malodour positive. DNA was extracted from the
      swab samples and analysed using next generation deep sequencing 16 s rDNA
      technology. Taxa identified could be classified into nine phyla, 29 genera and
      117 species. Malodour positive samples showed a higher abundance of the phyla
      Firmicutes and Fusobacteria and the genera Leptotrichia, Atopobium, Megasphaera,
      Oribacterium and Campylobacter. Microbiome analysis demonstrated higher bacterial
      diversity within the malodourous samples and a significant difference in the
      microbial profile within the two groups. Taken together these results suggest a
      difference between the microbial populations of malodourous and non-malodourous
      dentures both in composition and diversity.

PMID- 29341957
TI  - Multiple tuning of magnetic biskyrmions using in situ L-TEM in centrosymmetric
      MnNiGa alloy.
AB  - Magnetic skyrmions are topologically protected spin configurations and have
      recently received growingly attention in magnetic materials. The existence of
      biskyrmions within a broad temperature range has been identified in our newly
      discovered MnNiGa material, promising for potential application in physics and
      technological study. Here, the biskyrmion microscopic origination from the spin
      configuration evolution of stripe ground state is experimentally identified. The
      biskyrmion manipulations based on the influences of the basic microstructures and
      external factors such as grain boundary confinement, sample thickness, electric
      current, magnetic field and temperature have been systematically studied by using
      real-space Lorentz transmission electron microscopy. These multiple tuning
      options help to understand the essential properties of MnNiGa and predict a
      significant step forward for the realization of skyrmion-based spintronic
      devices.

PMID- 29341958
TI  - Persistent Asymptomatic Papules on the Chest.

PMID- 29341959
TI  - Indeterminate Dendritic Cell Sarcoma in a Patient With Myelodysplastic Syndrome.

PMID- 29341960
TI  - Sclerotic Ulcerated Plaque on the Back.

PMID- 29341961
TI  - An Unusual Vesiculopustular Eruption: Challenge.

PMID- 29341962
TI  - Withdrawal of life-sustaining therapy.
AB  - PURPOSE OF REVIEW: The aim of this review is to examine literature relating to
      the withdrawal of life-sustaining therapy (WLST). RECENT FINDINGS: Discussions
      regarding end-of-life issues in adults and children are not occurring
      comprehensively. Discussions relating to the WLST in the pediatric population
      varies by institution and may vary by race, age, health insurance, diagnosis, and
      severity of illness. Completing advance directives prior to placement of life
      sustaining treatments is not consistent practice. With the WLST, differences in
      perspectives exist between medical specialties, within one specialty at different
      levels of training, and in physicians' ethical and psychological responses to the
      WLST. The timing of WLST appears to be influenced by ICU strain and communication
      issues. Study outcomes differ regarding the functionally favorable survival of
      patients who have had WLST. Universal guidelines for the WLST may not address
      individual patient circumstances. SUMMARY: Discussions of end-of-life issues
      early in the course of a patient's health care will contribute to the healthcare
      team's understanding and respect of the patient's wishes. This article addresses
      the withdrawal of left ventricular assist devices; attending physicians and
      physicians in training perspectives of WLST; do physicians distinguish between
      withholding and WLST; the timing of WLST; guidelines for the process of WLST; and
      pediatrics and end-of-life decisions.

PMID- 29341963
TI  - Role of the anesthesiologist-intensivist outside the ICU: opportunity to add
      value for the hospital or an unnecessary distraction?
AB  - PURPOSE OF REVIEW: Given the extremely expensive nature of critical care
      medicine, it seems logical that intensivists should play an active role in
      designing efficient systems of care. The true value of intensivists, however, is
      not well defined. RECENT FINDINGS: Anesthesiologists have taken key roles in
      improving patient safety in the operating room. Anesthesia-related mortality
      rates have decreased from 20 deaths per 100 000 anesthetics in the early 1980s to
      less than one death per 100 000 currently. Anesthesiologist-intensivists remain
      rare (less than 5% of certified anesthesiologists), but increasingly play
      multiple roles within multidisciplinary teams. This review outlines the roles of
      intensivists in performance improvement, perioperative assessment; sedation
      services, extracorporeal and mechanical support, and code/rapid response teams.
      Critical-care physicians, by definition, work in collaborative multispecialty and
      multidisciplinary teams that make it difficult to isolate each team member's
      precise contribution to healthcare value. SUMMARY: Anesthesiologist-intensivists
      working outside their usual environment provide leadership and clinical guidance
      towards improving patient outcomes.

PMID- 29341964
TI  - Renal Decapsulation Prevents Intrinsic Renal Compartment Syndrome in Ischemia
      Reperfusion-Induced Acute Kidney Injury: A Physiologic Approach.
AB  - OBJECTIVES: Acute kidney injury is a serious complication with unacceptably high
      mortality that lacks of specific curative treatment. Therapies focusing on the
      hydraulic behavior have shown promising results in preventing structural and
      functional renal impairment, but the underlying mechanisms remain understudied.
      Our goal is to assess the effects of renal decapsulation on regional
      hemodynamics, oxygenation, and perfusion in an ischemic acute kidney injury
      experimental model. METHODS: In piglets, intra renal pressure, renal tissue
      oxygen pressure, and dysoxia markers were measured in an ischemia-reperfusion
      group with intact kidney, an ischemia-reperfusion group where the kidney capsule
      was removed, and in a sham group. RESULTS: Decapsulated kidneys displayed an
      effective reduction of intra renal pressure, an increment of renal tissue oxygen
      pressure, and a better performance in the regional delivery, consumption, and
      extraction of oxygen after reperfusion, resulting in a marked attenuation of
      acute kidney injury progression due to reduced structural damage and improved
      renal function. CONCLUSIONS: Our results strongly suggest that renal
      decapsulation prevents the onset of an intrinsic renal compartment syndrome after
      ischemic acute kidney injury.

PMID- 29341966
TI  - Surveying the Literature: Synopsis of Recent Key Publications.

PMID- 29341965
TI  - Osmotic Shifts, Cerebral Edema, and Neurologic Deterioration in Severe Hepatic
      Encephalopathy.
AB  - OBJECTIVES: We sought to determine the effect of acute electrolyte and osmolar
      shifts on brain volume and neurologic function in patients with liver failure and
      severe hepatic encephalopathy. DESIGN: Retrospective analysis of brain CT scans
      and clinical data. SETTING: Tertiary care hospital ICUs. PATIENTS: Patients with
      acute or acute-on-chronic liver failure and severe hepatic encephalopathy.
      INTERVENTIONS: Clinically indicated CT scans and serum laboratory studies.
      MEASUREMENTS AND MAIN RESULTS: Change in intracranial cerebrospinal fluid volume
      between sequential CT scans was measured as a biomarker of acute brain volume
      change. Corresponding changes in serum osmolality, chemistry measurements, and
      Glasgow Coma Scale were determined. Associations with cerebrospinal fluid volume
      change and Glasgow Coma Scale change for initial volume change assessments were
      identified by Spearman's correlations (rs) and regression models. Consistency of
      associations with repeated assessments was evaluated using generalized estimating
      equations. Forty patients were included. Median baseline osmolality was elevated
      (310 mOsm/Kg [296-321 mOsm/Kg]) whereas sodium was normal (137 mEq/L [134-142
      mEq/L]). Median initial osmolality change was 9 mOsm/kg (5-17 mOsm/kg).
      Neuroimaging consistent with increased brain volume occurred in 27 initial
      assessments (68%). Cerebrospinal fluid volume change was more strongly correlated
      with osmolality (r = 0.70; p = 4 * 10) than sodium (r = 0.28; p = 0.08) change.
      Osmolality change was independently associated with Glasgow Coma Scale change (p
      = 1 * 10) and cerebrospinal fluid volume change (p = 2.7 * 10) in initial
      assessments and in generalized estimating equations using all 103 available
      assessments. CONCLUSIONS: Acute decline in osmolality was associated with brain
      swelling and neurologic deterioration in severe hepatic encephalopathy.
      Minimizing osmolality decline may avoid neurologic deterioration.

PMID- 29341968
TI  - And Before That.

PMID- 29341967
TI  - New Modalities for the Administration of Inhaled Nitric Oxide in Intensive Care
      Units After Cardiac Surgery or for Neonatal Indications: A Prospective
      Observational Study.
AB  - BACKGROUND: Nitric oxide (NO) has a well-known efficacy in pulmonary hypertension
      (PH), with wide use for 20 years in many countries. The objective of this study
      was to describe the current use of NO in real life and the gap with the
      guidelines. METHODS: This is a multicenter, prospective, observational study on
      inhaled NO administered through an integrated delivery and monitoring device and
      indicated for PH according to the market authorizations. The characteristics of
      NO therapy and ventilation modes were observed. Concomitant pulmonary vasodilator
      treatments, safety data, and outcome were also collected. Quantitative data are
      expressed as median (25th, 75th percentile). RESULTS: Over 1 year, 236 patients
      were included from 14 equipped and trained centers: 117 adults and 81 children
      with PH associated with cardiac surgery and 38 neonates with persistent PH of the
      newborn. Inhaled NO was initiated before intensive care unit (ICU) admission in
      57%, 12.7%, and 38.9% with an initial dose of 10 (10, 15) ppm, 20 (18, 20) ppm,
      and 17 (11, 20) ppm, and a median duration of administration of 3.9 (1.9, 6.1)
      days, 3.8 (1.8, 6.8) days, and 3.1 (1.0, 5.7) days, respectively, for the adult
      population, pediatric cardiac group, and newborns. The treatment was performed
      using administration synchronized to the mechanical ventilation. The dose was
      gradually decreased before withdrawal in 86% of the cases according to the usual
      procedure of each center. Adverse events included rebound effect for 3.4% (95%
      confidence interval [CI], 0.9%-8.5%) of adults, 1.2% (95% CI, 0.0%-6.7%) of
      children, and 2.6% (95% CI, 0.1%-13.8%) of neonates and methemoglobinemia
      exceeded 2.5% for 5 of 62 monitored patients. Other pulmonary vasodilators were
      associated with NO in 23% of adults, 95% of children, and 23.7% of neonates. ICU
      stay was respectively 10 (6, 22) days, 7.5 (5.5, 15) days, and 9 (8, 15) days and
      ICU mortality was 22.2%, 6.2%, and 7.9% for adults, children, and neonates,
      respectively. CONCLUSIONS: This study confirms the safety of NO therapy in the 3
      populations with a low rate of rebound effect. Gradual withdrawal of NO combined
      with pulmonary vasodilators are current practices in this population. The use of
      last-generation NO devices allowed good compliance with recommendations.

PMID- 29341969
TI  - Pursuing Normality: Reflections on Cancer Survivorship Care of Lymphoma
      Survivors.
AB  - BACKGROUND: The present study explored the reflections on cancer survivorship
      care of lymphoma survivors in active treatment. Lymphoma survivors have
      survivorship care needs, yet their participation in cancer survivorship care
      programs is still reported as low. OBJECTIVE: The aim of this study was to
      understand the reflections on cancer survivorship care of lymphoma survivors to
      aid the future planning of cancer survivorship care and overcome barriers to
      participation. METHODS: Data were generated in a hematological ward during 4
      months of ethnographic fieldwork, including participant observation and 46
      semistructured interviews with 9 lymphoma survivors. Interpretive description
      methodology and social practice theory guided the analytical framework. RESULTS:
      "Pursuing normality" was an overall finding and was comprised of 2 overarching
      patterns, "future prospects" and "survivorship care perceptions," both implying
      an influence on whether to participate in cancer survivorship care programs.
      Because of "pursuing normality," 8 of 9 participants opted out of cancer
      survivorship care programming due to prospects of "being cured" and perceptions
      of cancer survivorship care as "a continuation of the disease." CONCLUSION: The
      findings add to our understanding of possible barriers for participation in
      cancer survivorship care and outline important aspects to account for in the
      practice of health professionals. IMPLICATIONS FOR PRACTICE: The study findings
      may guide practice to establish a systematic approach for providing information
      to cancer survivors regarding the possible management of their symptoms and of
      the content and purpose of cancer survivorship care.

PMID- 29341970
TI  - Does the use of indirect calorimetry change outcome in the ICU? Yes it does.
AB  - PURPOSE OF REVIEW: To review the recent findings on metabolic monitoring and
      possible beneficial effects of an adequate nutrition therapy, based on indirect
      calorimetry as the golden standard to predict energy expenditure. RECENT
      FINDINGS: in the last decades, major steps are taken in the field of metabolism
      and nutrition, evolving from nutrition as a baseline support to a therapeutic
      intervention. The aspect of energy expenditure is of cardinal importance, and
      technical possibilities have impressively improved: from the first 'calorimetre'
      in 1789 to the new generation, clinical applicable indirect calorimeters and the
      high accuracy and easy use model reaching high technology readiness level [Oshima
      et al. (2017). Clin Nutr 36:651]. Several recent studies provide information on
      the technique of metabolic monitoring itself and the positive effects of
      implementation of the tool in a high-end nutritional care plan [Oshima et al.
      (2017). Clin Nutr 36:651]. The combination of correct energy provision and
      protein prescription has shown benefits, and mortality of ICU patients is related
      to the amount of energy provided [Zusman et al. (2016). Crit Care 20:367]. The
      use of a monitor per se will not change outcome. Optimal dosing of artificial
      nutrition can be achieved by the use of a parameter acquired by a measurement
      instead of by inaccurate equations. In the era of precision medicine, this
      approach has shown positive effects on outcome. Moreover, above all, the concept
      of metabolic monitoring of the critically ill is just an issue of common sense.
      SUMMARY: Metabolic monitoring by indirect calorimetry is achieving a level in
      which it can be implemented in critical care practice. Evidence is available to
      prove that by guiding your nutritional therapy by measured values, it will change
      outcome of critically ill patients.

PMID- 29341971
TI  - Atopy in Patients With Ocular Cicatricial Pemphigoid.
AB  - PURPOSE: To evaluate the presence of atopy in patients with ocular cicatricial
      pemphigoid (OCP). METHOD: Patient encounters between August 2005 and November
      2016 at the Massachusetts Eye Research and Surgery Institute (MERSI) were
      searched to identify those with biopsy-proven OCP who had concurrent evidence of
      atopy. RESULTS: There were 230 patients with biopsy-proven OCP. Thirty-three of
      them were found to have clinical symptoms of atopy (asthma, hay fever, and
      eczema) and of these, 23 had evidence of atopy in their conjunctival biopsy
      specimens. All patients were administered immunomodulatory therapy for treatment
      of their OCP with 20 patients requiring additional antiallergy treatment to
      control residual atopic ocular symptoms. Among patients who used antiallergy
      medications, 80% showed improvement in residual symptoms. Rituximab and/or
      intravenous immunoglobulin is a preferred OCP medication for patients with OCP
      with some evidence of atopy. CONCLUSIONS: Clinicians should consider the
      coexistence of atopy in patients with OCP, especially in those with persistent
      symptoms after initiation of immunomodulatory therapy.

PMID- 29341972
TI  - Ocular Surface and Tear Film Characteristics in a Sclerodermatous Chronic Graft
      Versus-Host Disease Mouse Model.
AB  - PURPOSE: To report the characteristics of the ocular surface in a previously
      established sclerodermatous chronic graft-versus-host disease (cGVHD) mouse
      model. METHODS: The ocular surface features and tear film parameters of the mouse
      model were assessed by histopathology, immunohistochemistry, electron microscopy,
      quantitative polymerase chain reaction, and flow cytometry. RESULTS: The mice
      exhibited loss of body weight and decreased tear secretion (P < 0.001), mimicking
      the clinical features of patients with cGVHD. Ocular examination demonstrated
      significant corneal epithelial staining, conjunctival (P < 0.001), and eyelid (P
      = 0.015) fibrosis compared with the control mice. The density of both goblet
      cells (P = 0.043) and microvilli was lower (P < 0.001), and the microvilli were
      shorter (P = 0.007) in the conjunctiva of cGVHD mice than those of the controls.
      The immunohistochemical studies demonstrated greater expression of CD45, CD4, and
      CD8 cells in the conjunctiva and eyelid tissues compared with the controls (P <
      0.05 for all). In addition, reduced Forkhead box P3 (Foxp3)+ cells were found in
      both the peripheral blood (P < 0.001) and conjunctiva (P = 0.042) of cGVHD mice
      compared with the controls. CONCLUSIONS: The constellation of these findings
      suggests that the sclerodermatous cGVHD mouse model well recapitulates ocular
      manifestations of cGVHD in humans. This model can be used to study the mechanisms
      involved in the pathogenesis and treatment of chronic ocular graft-versus-host
      disease.

PMID- 29341973
TI  - Detection and Imaging of Lymphatic and Other Vessels in Corneal Neovascular
      Complexes.

PMID- 29341974
TI  - Feasibility and Effectiveness of Continuing Methadone Maintenance Treatment
      During Incarceration Compared With Forced Withdrawal.
AB  - BACKGROUND: Methadone maintenance treatment (MMT) is underutilized in
      correctional settings, and those receiving MMT in the community often undergo
      withdrawal upon incarceration. Federal and state regulations present barriers to
      providing methadone in correctional facilities. For this investigation, a
      community provider administered methadone to inmates who had been receiving
      methadone prior to incarceration. We hypothesized that inmates continued on MMT
      would have improved behavior during incarceration and post-release. METHODS: This
      open-label quasi-experimental trial (n = 382) compared MMT continuation
      throughout incarceration (n = 184) to an administrative control group (ie, forced
      withdrawal; n = 198) on disciplinary tickets and other program attendance during
      incarceration. Post-release, re-engagement in community-based MMT and 6-month
      recidivism outcomes were evaluated. RESULTS: Inmates in the MMT continuation
      group versus controls were less likely to receive disciplinary tickets (odds
      ratio [OR] = 0.32) but no more likely to attend other programs while
      incarcerated. MMT continuation increased engagement with a community MMT provider
      within 1 day of release (OR  = 32.04), and 40.6% of MMT participants re-engaged
      within the first 30 days (vs 10.1% of controls). Overall, re-engagement in MMT
      was not associated with recidivism. However, among a subset of inmates who
      received MMT post-incarceration from the jail MMT provider (n = 69), re
      engagement with that provider was associated with reduced risk of arrest, new
      charges, and re-incarceration compared with those who did not re-engage.
      CONCLUSIONS: Results support interventions that facilitate continuity of MMT
      during and after incarceration. Engagement of a community provider is feasible
      and can improve access to methadone in correctional facilities.

PMID- 29341975
TI  - Validation of a Simplified Implant-Retained Cantilever Fixed Prosthesis.
AB  - PURPOSE: To evaluate the stress and strain generated in a fixed four-element
      prosthesis under the application of axial and nonaxial loads using a simplified
      implant-supported fixed prosthesis model. MATERIALS AND METHODS: A 3-dimensional
      model was constructed containing 3 implants with a conventional anatomical
      prosthesis (G1). The second model with the same implant system received the
      simplified prosthesis (G2). A load of 300 N was applied at an axial point and a
      nonaxial point through finite element analysis software. RESULTS: The G2 group
      showed different values of stress concentration in the prosthesis, fixation
      screw, retention screw, and abutments when compared with G1. Within a limit of
      10% degrees of acceptability, the stress on the implants and the bone strain were
      enclosed for both models of prostheses. CONCLUSION: The simplified fixed
      prosthesis evaluated presents biomechanical behavior similar to an anatomical
      prosthesis in the implants and in the surrounding bone structure.

PMID- 29341976
TI  - Cone-Beam CT Assessment of the Position of the Medial Lingual Foramen for Dental
      Implant Placement in the Anterior Symphysis.
AB  - OBJECTIVES: To determine the position of the mandibular medial lingual foramen
      with cone-beam CT (CBCT) 3D imaging modalities when implants are to be placed in
      the anterior symphysis of the mandible. MATERIALS AND METHODS: A total of 111
      CBCTs were considered acceptable and analyzed. The variables measured were as
      follows: (1) length of the outlet duct; (2) distance from the canal to the buccal
      cortex; (3) distance from the canal to the inferior cortex; (4) distance from the
      canal to the lingual cortex; (5) distance from the canal to the alveoli of the
      nearest tooth in dentate patients and distance from the canal to the marginal
      crest in edentulous patients; (6) angle of the duct to the horizontal Frankfurt
      plane; (7) diameter of the exit orifice; and (8) output level of the socket in
      relation to the teeth and the presence of bifurcations. RESULTS: A single canal
      was observed in 64% of patients; 2 canals were observed in 33% of patients; and a
      triple foramen was observed in 3% of patients. Women showed slightly lower values
      than men for each of the analyzed variables, with statistically significant
      differences in the length of the canal in edentulous (P = 0.029) and dentate
      patients (P = 0.027). CONCLUSION: The medial lingual foramen should be considered
      while performing presurgical planning. Careful attention is needed while setting
      the placement position of the dental implant to decrease the risk of
      complications.

PMID- 29341977
TI  - Elemental Composition at Silicone Hydrogel Contact Lens Surfaces.
AB  - OBJECTIVES: The outermost surface composition of 11 silicone hydrogel (SiHy)
      lenses was measured using X-ray photoelectron spectroscopy (XPS) to understand
      differences in wettability and potential interactions within an ocular
      environment. The SiHy lenses tested included balafilcon A, lotrafilcon A,
      lotrafilcon B, senofilcon A, comfilcon A, and somofilcon A reusable 2-week or
      monthly replacement lenses and delefilcon A, samfilcon A, narafilcon A,
      stenfilcon A, and somofilcon A daily disposable lenses. METHODS: All lenses were
      soaked for 24 hr in phosphate-buffered saline to remove all packaging solution
      and dried under vacuum overnight before analysis. X-ray photoelectron
      spectroscopy measurements were performed at 2 take-off angles, 55 degrees  and 75
      degrees , to evaluate changes in elemental composition as a function of depth
      from the surface. RESULTS: Detailed analysis of the XPS data revealed distinct
      differences in the chemical makeup of the different lens types. For all lenses,
      carbon, oxygen, and nitrogen were observed in varying quantities. In addition,
      fluorine was detected at the outermost surface region of comfilcon A (3.4%) and
      lotrafilcon A and B (<0.5%). The silicon content of the near-surface region
      analyzed varied among lens types, ranging from a low of 1.6% (lotrafilcon B) to a
      high of 16.5% (comfilcon A). In most instances, silicon enrichment at the
      outermost surface was observed, resulting from differences in lens formulation
      and design. CONCLUSIONS: Lenses differed most in their surface silicon
      concentration, with lotrafilcon B and delefilcon A exhibiting the lowest silicon
      contents and comfilcon A lens exhibiting the highest. Silicon has hydrophobic
      properties, which, when found at the surface, may influence the wettability of
      the contact lenses and their interaction with the tear film and ocular tissues.
      Higher surface silicon contents have been previously correlated with adverse
      effects, such as enhanced lipid uptake, thus underscoring the importance of
      monitoring their presence.

PMID- 29341978
TI  - Assessment of Clinical Trials for Devices Intended to Control Myopia Progression
      in Children.
AB  - The increased prevalence of myopia in the United States and other regions of the
      world, and the sight-threatening problems associated with higher levels of myopia
      have led to great interest in research designed to reduce these rates. As most of
      the progression of myopia occurs in childhood, these investigations have been
      directed toward slowing the progression of myopia in children. Treatments
      described to potentially slow the progression of myopia have included
      pharmacological interventions, multifocal spectacles, and multifocal correction
      created by contact lenses. Although some contact lens clinical trials have
      demonstrated promising results in slowing the progression of myopia, many of
      these studies have significant limitations, including only short follow-up times,
      limited randomization, and incomplete masking. Such limitations have underscored
      the need to develop a more robust clinical study design, so that future studies
      can demonstrate whether contact lenses, as well as other medical devices, can be
      used in a safe and effective manner to control myopia progression. We review
      previous key studies and discuss study design and regulatory issues relevant to
      future clinical trials.

PMID- 29341979
TI  - Wilson's Disease in Children: A Position Paper by the Hepatology Committee of the
      European Society for Paediatric Gastroenterology, Hepatology and Nutrition.
AB  - BACKGROUND: Clinical presentations of Wilson's disease (WD) in childhood ranges
      from asymptomatic liver disease to cirrhosis or acute liver failure, whereas
      neurological and psychiatric symptoms are rare. The basic diagnostic approach
      includes serum ceruloplasmin and 24-hour urinary copper excretion. Final
      diagnosis of WD can be established using a diagnostic scoring system based on
      symptoms, biochemical tests assessing copper metabolism, and molecular analysis
      of mutations in the ATP7B gene. Pharmacological treatment is life-long and aims
      at removal of copper excess by chelating agents as D-penicillamine, trientine, or
      inhibition of intestinal copper absorption with zinc salts. Acute liver failure
      often requires liver transplantation. This publication aims to provide
      recommendations for diagnosis, treatment, and follow-up of WD in children.
      METHODS: Questions addressing the diagnosis, treatment, and follow-up of WD in
      children were formulated by a core group of ESPGHAN members. A systematic
      literature search on WD using MEDLINE, EMBASE, Cochrane Database from 1990 to
      2016 was performed focusing on prospective and retrospective studies in children.
      Quality of evidence was assessed according to the GRADE system. Expert opinion
      supported recommendations where the evidence was regarded as weak. The ESPGHAN
      core group and ESPGHAN Hepatology Committee members voted on each recommendation,
      using the nominal voting technique.

PMID- 29341980
TI  - How Much Free Sugars Intake Should Be Recommended for Children Younger Than 2
      Years Old?

PMID- 29341981
TI  - Response to Letter: How Much Free Sugars Intake Should Be Recommended for
      Children Younger Than Two Years Old?

PMID- 29341982
TI  - Extensive Necrotic Skin Lesions Due to Post-varicella Protein S Deficiency.
AB  - Postvaricella protein S deficiency is a rare and severe disease. We report a case
      of extensive necrotic skin lesions of acute onset 7 days after varicella in a 4
      year-old girl. Protein S antigen and activity were <10%, and antiprotein S
      antibodies were detected. She was treated with anticoagulation, plasmapheresis
      and fresh frozen plasma. She survived but required leg amputation.

PMID- 29341983
TI  - Diarrheagenic Escherichia coli and Acute Gastroenteritis in Children in Davidson
      County, Tennessee, United States: A Case-control Study.
AB  - BACKGROUND: Diarrheagenic Escherichia coli (DEC) is an important cause of acute
      gastroenteritis in children; however, there is limited information available on
      the epidemiology, phylogenetics, serotyping and antibiotic susceptibility of DEC
      in children in the United States. The aim of this study was to determine the
      molecular epidemiology of DEC among children with and without acute
      gastroenteritis in Davidson County, Tennessee. METHODS: This prospective,
      frequency matched, case-control study recruited subjects 15 days to 17 years of
      age and detected DEC with polymerase chain reaction from stool samples.
      Additional testing was done to define phylogenetics and antibiotics resistance.
      RESULTS: Among 1267 participants, 857 cases and 410 controls, 5.5% were positive
      for at least one subtype of DEC. Enteroaggregative E. coli [n = 32 (45%)] was the
      most common subtype followed by enteropathogenic E. coli (EPEC) [n = 30 (43%)],
      Shiga toxin-producing E. coli [n = 4 (6%)] and diffusely adherent E. coli [n = 4
      (6%)]. No significant difference in prevalence of DEC was found between cases
      (5%) and controls (7%) [odds ratio: 0.66 (95% confidence interval: 0.4-1.07)],
      and results were similar when data were stratified by subtypes and adjusted for
      age, sex, race and ethnicity. Substantial diversity was found among DEC isolates
      in terms of phylotypes and serotypes, and a large proportion was resistant to, at
      least, one antibiotic. CONCLUSIONS: Enteroaggregative E. coli and
      enteropathogenic E. coli were frequently found in both cases and controls in this
      study population. DNA-based methods for detection of these subtypes need further
      investigation to help differentiate between pathogenic and colonizing strains.

PMID- 29341984
TI  - Effect of Age at Vaccination on Rotavirus Vaccine Effectiveness in Bolivian
      Infants.
AB  - BACKGROUND: Rotavirus vaccines are less effective in developing countries versus
      developed countries. One hypothesis for this difference in performance is that
      higher levels of maternal antibodies in developing countries may interfere with
      vaccine response, suggesting that delayed dosing could be beneficial. The present
      analysis aims to assess whether rotavirus vaccine effectiveness (VE) varies by
      age at vaccination during routine use in Bolivia. METHODS: Data were merged from
      2 postlicensure evaluations of monovalent rotavirus vaccine (RV1) in Bolivia,
      where 2 doses of RV1 are recommended at 2 and 4 months of age. For each dose,
      children were classified as receiving each dose "early," "on-time" or "late."
      Stratified unconditional logistic regression models were used to estimate VE,
      using unvaccinated children as the referent. VE was calculated as (1 - odds
      ratio) * 100%. Models were adjusted for hospital, age and time since RV1
      introduction (via including terms for month and year of birth). RESULTS: VE for 2
      doses of RV1 tended to be higher in infants receiving the first dose early (VE,
      92%; 95% confidence interval: 70%-98%), when compared with infants receiving
      their first dose on-time [72% (62%-81%)] or late [68% (51%-79%)]. Estimates of VE
      were not substantially different when comparing children by age at second dose
      [early: VE, 76% (50%-89%); on-time: VE, 70% (50%-89%); late: VE, 75% (60%, 84%)],
      including all children. CONCLUSIONS: Our results indicate that early
      administration may improve VE and support the current World Health Organization
      recommendations for the RV1 schedule.

PMID- 29341985
TI  - Dexmedetomidine as Single Continuous Sedative During Noninvasive Ventilation:
      Typical Usage, Hemodynamic Effects, and Withdrawal.
AB  - OBJECTIVES: Dexmedetomidine use in pediatric critical care is increasing. Its
      prolonged effects as a single continuous agent for sedation are not well
      described. The aim of the current study was to describe prolonged dexmedetomidine
      therapy without other continuous sedation, specifically the hemodynamic effects,
      discontinuation strategies, and risk factors for withdrawal. DESIGN:
      Retrospective chart review. SETTING: Large, single-center, quaternary care
      pediatric academic institution. PATIENTS: Data from 382 children, less than 18
      years old admitted to the PICU who received dexmedetomidine for more than 24
      hours without other infusions for sedation during noninvasive positive pressure
      ventilation. INTERVENTIONS: Usual care practices for dexmedetomidine use were
      described. Discontinuation strategies were categorized as abrupt discontinuation,
      wean from dexmedetomidine infusion, and transition to enteral clonidine.
      MEASUREMENTS AND MAIN RESULTS: Median peak and cumulative doses with
      interquartile range were 1 ug/kg/hr (0.6-1.2 ug/kg/hr) and 30 ug/kg (20-50
      ug/kg), respectively, and median duration was 45 hours (34-66 hr). Four hours
      after reaching peak dose, we observed a decrease in heart rate (p < 0.01) with
      28% prevalence of bradycardia and an increase in systolic blood pressure (p <
      0.01) with 33% prevalence of hypertension and 2% hypotension. During the
      escalation phase, the prevalence of bradycardia and hypotension were 75% and a
      30%, respectively. Three-hundred thirty-six patients (88%) had abrupt
      discontinuation, 37 (10%) were weaned, and nine (2%) were transitioned to
      clonidine. Nineteen patients (5%) experienced withdrawal. Univariate risk of
      withdrawal was most associated with duration: odds ratio equal to 1.5 (1.3-1.7)
      for each 12-hour period (p < 0.01). By multivariate analysis including age,
      discontinuation group, dexmedetomidine cumulative dose, and peak dose, only
      cumulative dose remained significant with an odds ratio equal to 1.3 (1.1-1.5)
      for each 10 MUg/kg (p < 0.01). CONCLUSIONS: Dexmedetomidine use for noninvasive
      positive pressure ventilation sedation in pediatric critical care has predictable
      hemodynamic effects including bradycardia and hypertension. Although withdrawal
      was associated with higher cumulative dose, these symptoms were effectively
      managed with short-term enteral clonidine.

PMID- 29341987
TI  - BSN in 10: It's the law!

PMID- 29341986
TI  - Pulmonary Dead Space Fraction and Extubation Success in Children After Cardiac
      Surgery.
AB  - OBJECTIVES: 1) Determine the correlation between pulmonary dead space fraction
      and extubation success in postoperative pediatric cardiac patients; and 2)
      document the natural history of pulmonary dead space fractions, dynamic
      compliance, and airway resistance during the first 72 hours postoperatively in
      postoperative pediatric cardiac patients. DESIGN: A retrospective chart review.
      SETTING: Cardiac ICU in a quaternary care free-standing children's hospital.
      PATIENTS: Twenty-nine with balanced single ventricle physiology, 61 with two
      ventricle physiology. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We
      collected data for all pediatric patients undergoing congenital cardiac surgery
      over a 14-month period during the first 72 hours postoperatively as well as prior
      to extubation. Overall, patients with successful extubations had lower
      preextubation dead space fractions and shorter lengths of stay. Single ventricle
      patients had higher initial postoperative and preextubation dead space fractions.
      Two-ventricle physiology patients had higher extubation failure rates if the
      preextubation dead space fraction was greater than 0.5, whereas single ventricle
      patients had similar extubation failure rates whether preextubation dead space
      fractions were less than or equal to 0.5 or greater than 0.5. Additionally,
      increasing initial dead space fraction values predicted prolonged mechanical
      ventilation times. Airway resistance and dynamic compliance were similar between
      those with successful extubations and those who failed. CONCLUSIONS: Initial
      postoperative dead space fraction correlates with the length of mechanical
      ventilation in two ventricle patients but not in single ventricle patients. Lower
      preextubation dead space fractions are a strong predictor of successful
      extubation in two ventricle patients after cardiac surgery, but may not be as
      useful in single ventricle patients.

PMID- 29341989
TI  - A private case of allergic contact dermatitis.

PMID- 29341988
TI  - Utilizing advance care planning codes.

PMID- 29341990
TI  - Non-fasting versus fasting cholesterol measurement.
AB  - Fasting for cholesterol measurement has long been the accepted convention. Recent
      research expounded in clinical guidelines indicates that nonfasting cholesterol
      measurements predict outcomes at least as well as fasting cholesterol
      measurements. In most-but not all-clinical scenarios, fasting is not necessary.
      This article provides clinical recommendations based on the literature.

PMID- 29341991
TI  - Autism spectrum disorder in primary care.

PMID- 29341992
TI  - Periodontal disease in children with type 2 diabetes mellitus.

PMID- 29341993
TI  - Examining changes to statewide NP practice in Connecticut.
AB  - In 2014, Connecticut legislators eliminated the need for advanced practice
      registered nurses with 2,000 practice hours to obtain collaborative practice
      agreements with physicians. This study examined resulting practice changes,
      barriers, and suggestions for improved implementation of independent practice.
      Thirteen NPs participated in focus groups to share their experiences and
      recommendations.

PMID- 29341994
TI  - Understanding tuberculosis in an era of global travel.
AB  - With the resurgence of tuberculosis (TB), it is imperative that healthcare
      providers have the necessary skills to manage the specialized issues of
      prevention, recognition, and treatment of TB. The case study in this article
      illustrates these skills for NPs and other advanced practice providers.

PMID- 29341996
TI  - Retinal Arterio-Arterial Collaterals in Susac Syndrome.
AB  - BACKGROUND: The ophthalmic findings of Susac syndrome (SS) consist of visual
      field defects related to branch retinal artery occlusion (BRAO), and fluorescein
      angiography (FA) reveals a unique staining pattern. To date, retinal arterial
      collateral development has been described only in a single patient. Given that
      the immunopathological process in SS induces retinal ischemia, it is conceivable
      that abnormal blood vessel development may occur in affected individuals.
      METHODS: This is a retrospective observational study. The medical records
      including fundus photography and FA of all patients with SS were reviewed, and
      those with any type of retinal arterial collateral were identified. RESULTS: A
      total of 11 patients were identified with retinal collaterals. Five were men. Age
      ranged from 20 to 50 years. Ten patients had arterio-arterial (A-A) collaterals
      and 1 had arterio-venous (A-V) collaterals, and all had collaterals remote from
      the optic disc. No collaterals were present at onset of illness and the first
      developed at 9 months. CONCLUSIONS: The literature reveals scant evidence for the
      association between BRAO and retinal arterial collaterals. Our findings indicate
      that retinal arterial collaterals in SS are usually A-A and not A-V and may be
      more common in this disorder than previously believed. Collaterals do not develop
      early in the disease, and there may be a predilection toward development in men.
      The chronic inflammatory state of SS may be the stimulus for the development of
      these arterial collaterals.

PMID- 29341997
TI  - Literature Commentary.
AB  - In this issue of Journal of Neuro-Ophthalmology, M. Tariq Bhatti, MD and Mark L.
      Moster, MD will discuss the following 6 articles.

PMID- 29341998
TI  - Learning From Pediatrics to Secure Medical Education for the Future.

PMID- 29341999
TI  - Unlocking the Closet Door: Recurrent Identity Disclosure Experiences Among LGBTQ
      Students.

PMID- 29342000
TI  - From Subsistence to Sustenance in Physician-Scientist Training.

PMID- 29342001
TI  - Beyond USMLE Step 1.

PMID- 29342002
TI  - Finding Focus: Recruiting and Supporting Underrepresented Minority Trainees
      Starts With Faculty.

PMID- 29342003
TI  - How to Maximize Happiness, Stability, and Success Among Medical School
      Applicants.

PMID- 29342004
TI  - The Privilege of Patient Care: Often Experienced, Rarely Discussed.

PMID- 29342005
TI  - From Theoretical Physics to Atomic Bombs: Learning to Value Medical Epistemology.

PMID- 29342006
TI  - On Transitions in Training: Boost Bioethics Education.

PMID- 29342007
TI  - Learning to Teach.

PMID- 29342008
TI  - The R2C2 Model in Residency Education: How Does It Foster Coaching and Promote
      Feedback Use?
AB  - PURPOSE: The authors previously developed and tested a reflective model for
      facilitating performance feedback for practice improvement, the R2C2 model. It
      consists of four phases: relationship building, exploring reactions, exploring
      content, and coaching. This research studied the use and effectiveness of the
      model across different residency programs and the factors that influenced its
      effectiveness and use. METHOD: From July 2014-October 2016, case study
      methodology was used to study R2C2 model use and the influence of context on use
      within and across five cases. Five residency programs (family medicine,
      psychiatry, internal medicine, surgery, and anesthesia) from three countries
      (Canada, the United States, and the Netherlands) were recruited. Data collection
      included audiotaped site assessment interviews, feedback sessions, and debriefing
      interviews with residents and supervisors, and completed learning change plans
      (LCPs). Content, thematic, template, and cross-case analysis were conducted.
      RESULTS: An average of nine resident-supervisor dyads per site were recruited.
      The R2C2 feedback model, used with an LCP, was reported to be effective in
      engaging residents in a reflective, goal-oriented discussion about performance
      data, supporting coaching, and enabling collaborative development of a change
      plan. Use varied across cases, influenced by six general factors: supervisor
      characteristics, resident characteristics, qualities of the resident-supervisor
      relationship, assessment approaches, program culture and context, and supports
      provided by the authors. CONCLUSIONS: The R2C2 model was reported to be effective
      in fostering a productive, reflective feedback conversation focused on resident
      development and in facilitating collaborative development of a change plan.
      Factors contributing to successful use were identified.

PMID- 29342009
TI  - How Academic Health Systems Can Achieve Population Health in Vulnerable
      Populations Through Value-Based Care: The Critical Importance of Establishing
      Trusted Agency.
AB  - Improving population health may require health systems to proactively engage
      patient populations as partners in the implementation of healthy behaviors as a
      shared value using strategies that incentivize healthy outcomes for the
      population as a whole. The current reactive health care model, which focuses on
      restoring the health of individuals after it has been lost, will not achieve the
      goal of improved population health. To achieve this goal, health systems must
      proactively engage in partnerships with the populations they serve. Health
      systems will need the help of community entities and individuals who have the
      trust of the population being served and are willing to act on behalf of the
      health system if they are to achieve this effective working partnership. The need
      for these trusted agents is particularly pertinent for vulnerable and
      historically underserved segments of the population. In this Invited Commentary,
      the authors discuss ways by which health systems might identify, engage, and
      leverage trusted agents to improve the health of the population through value
      based care.

PMID- 29342010
TI  - The ever-expanding saga of the proprotein convertases and their roles in body
      homeostasis: emphasis on novel proprotein convertase subtilisin kexin number 9
      functions and regulation.
AB  - PURPOSE OF REVIEW: The nine members of the proprotein convertase family play
      major physiological roles during development and in the adult, and their
      dysregulation leads to various diseases. The primary objective of this article is
      to review recent findings on the clinical importance of some of these convertases
      concentrating mostly on PCSK9, the ninth member of the convertase family. This
      includes the transcriptional and translational regulation of PCSK9, its ability
      to enhance the degradation of LDL receptor (LDLR), and the implication of PCSK9
      in inflammation and sepsis. RECENT FINDINGS: PCSK9 levels are upregulated by E2F1
      and reduced by specific miRNAs and by Annexin A2 that bind the 3' end of its
      mRNA. The implication of the LDLR in the clearance of pathogenic bacterial debris
      in mice and human puts in perspective a new role for PCSK9 in the regulation of
      sepsis. The specific implication of the LDLR in the clearance of Lp(a) is now
      confirmed by multiple studies of PCSK9 inhibition in human cohorts. SUMMARY:
      Emerging data suggest that PCSK9 can be regulated at the transcriptional and
      translational levels by specific factors and miRNAs. The identification of a
      novel pocket in the catalytic domain of PCSK9 represents a harbinger for a new
      class of small inhibitor drugs. The implication of the LDLR in reducing the
      effects of bacterially induced sepsis has been supported by both human and mouse
      data. Outcome studies confirmed the clinical importance of reducing PCSK9 levels.
      The present review puts in perspective new developments in the PCSK9 biology and
      its regulation of the LDLR. VIDEO ABSTRACT: http://links.lww.com/COL/A17.

PMID- 29342011
TI  - Utility of Time and Frequency Domain Parameters of Heart Rate Variability in the
      Context of Autonomic Disorders Characterized by Orthostatic Dysfunction.
AB  - PURPOSE: The clinical significance of heart rate variability in the context of
      autonomic dysfunction continues to be a matter of debate. A consensus is lacking
      on the best heart rate variability measures for clinical purposes. Therefore, the
      purpose of this study was to investigate the utility of heart rate variability
      parameters in healthy versus autonomic dysfunction. METHODS: Healthy young (n =
      134), healthy older (n = 32), and patients with mild (postural tachycardia
      syndrome; n = 25) and severe (neurogenic orthostatic hypotension; n = 34)
      autonomic dysfunction were included. Time and frequency parameters during
      baseline, head-up tilt (HUT), and heart rate response to deep breathing (HRDB)
      were compared. RESULTS: Cardiovagal time parameters were significantly reduced
      during HUT in healthy young and postural tachycardia syndrome (P < 0.001).
      Healthy young had significantly higher time parameters during baseline, HUT, and
      HRDB (P < 0.01). This was reflected by a significantly lower resting heart rate
      (HR) (61.4 +/- 9.0 bpm vs. 76.8 +/- 13.6 bpm; P < 0.001) and a smaller
      [INCREMENT]HR during HUT (32.8 +/- 10.5 bpm vs. 44.4 +/- 13.3 bpm; P < 0.001).
      Time parameters increased in young and postural tachycardia syndrome during HRDB,
      which was characterized by a nonsignificant difference in [INCREMENT]HR between
      both groups. Time parameters were significantly higher in healthy old versus
      neurogenic orthostatic hypotension at rest and during HRDB (P < 0.05). During
      HUT, only the SD of all normal RR intervals remained significantly higher. Heart
      rate changes corroborated these findings. Resting HR was significantly lower in
      healthy older (62.6 +/- 11.0 bpm vs. 70.7 +/- 12.4 bpm), and [INCREMENT]HR during
      HRDB was significantly higher (15.9 +/- 9.2 bpm vs. 3.9 +/- 4.2 bpm; P < 0.001).
      During HUT, [INCREMENT]HR showed no significant differences. CONCLUSIONS: Time
      domain parameters of heart rate variability have a greater utility than frequency
      parameters in clinical autonomic disorders.

PMID- 29342013
TI  - Development of Minimally Invasive Surgery at Johns Hopkins.

PMID- 29342012
TI  - DIFFUSE CHORIORETINOPATHY WITHOUT SEROUS DETACHMENT ASSOCIATED WITH CARDIAC
      TRANSPLANTATION.
AB  - PURPOSE: To analyze an unusual case of widespread chorioretinopathy after cardiac
      transplantation for its potential etiology and clinical significance. METHODS:
      Clinical examinations included widefield and macular color and fundus
      autofluorescence photography, spectral domain optical coherence tomography,
      fluorescein angiography and indocyanine green angiography, full-field
      electroretinography, and Goldmann visual fields. PATIENT: A 44-year-old Hispanic
      woman was referred to rule out retinitis pigmentosa. Medical history revealed
      cardiac transplantation 6 months previously for idiopathic cardiomyopathy.
      RESULTS: Visual acuity was 20/20 in both eyes. The fundi showed widespread gray
      mottling and little pigmentation, but fundus autofluorescence revealed black
      speckling broadly across the fundus, and geographic retinal pigment epithelium
      loss in the nasal midperiphery of the left eye. Spectral domain optical coherence
      tomography showed normal inner retina, and surprising preservation of outer
      nuclear layer, but the ellipsoid zone line was fragmented, and the
      interdigitation zone line was replaced with irregular debris. Retinal pigment
      epithelium was very thin with occasional excrescences. Electroretinography showed
      mild loss of both rods and cones, with mild flicker peak delay only in the left
      eye. Fluorescein angiography showed no leakage, but a reticular pigment pattern
      in the macula. Indocyanine green angiography showed irregular arteriolar
      remodeling, and few large arteries. DISCUSSION AND CONCLUSION: Serous retinopathy
      is well known after organ transplantations, but this patient had retinal pigment
      epithelium and retinal damage well into the periphery and no leakage. Retinal
      dystrophy was deemed unlikely given the relatively good electroretinography. The
      indocyanine green vascular changes raise the possibility of a transient choroidal
      ischemic event during or shortly after cardiac surgery. The event altered retinal
      pigment epithelium diffusely, but allowed for enough regeneration to sustain
      retinal function. Diffuse transplant chorioretinopathy may be discovered if
      postcardiac transplant patients get peripheral retinal examinations.

PMID- 29342015
TI  - Post-treatment/Pre-operative PET Response Is Not an Independent Predictor of
      Outcomes for Patients With Gastric and GEJ Adenocarcinoma.

PMID- 29342014
TI  - Patterns and Predictors of Return to Work After Major Trauma: A Prospective,
      Population-based Registry Study.
AB  - OBJECTIVE: To characterize patterns of engagement in work during the 4-year
      period after major traumatic injury, and to identify factors associated with
      those patterns. BACKGROUND: Employment is an important marker of functional
      recovery from injury. There are few population-based studies of long-term
      employment outcomes, and limited data on the patterns of return to work (RTW)
      after injury. METHODS: A population-based, prospective cohort study using the
      Victorian State Trauma Registry. A total of 1086 working age individuals, in paid
      employment or full-time education before injury, were followed-up through
      telephone interview at 6, 12, 24, 36, and 48 months post-injury. Responses to RTW
      questions were used to define 4 discrete patterns: early and sustained; delayed;
      failed; no RTW. Predictors of RTW patterns were assessed using multivariate
      multinomial logistic regression. RESULTS: Slightly more than half of respondents
      (51.6%) recorded early sustained RTW. A further 15.5% had delayed and 13.3%
      failed RTW. One in 5 (19.7%) did not RTW. Compared with early sustained RTW,
      predictors of delayed and no RTW included being in a manual occupation and injury
      in a motor vehicle accident. Older age and receiving compensation predicted both
      failed and no RTW patterns. Preinjury disability was an additional predictor of
      failed RTW. Presence of comorbidity was an additional predictor of no RTW.
      CONCLUSIONS: A range of personal, occupational, injury, health, and compensation
      system factors influence RTW patterns after serious injury. Early identification
      of people at risk for delayed, failed, or no RTW is needed so that targeted
      interventions can be delivered.

PMID- 29342016
TI  - Unresectable Colorectal Liver Metastases: When Definitions Matter to
      Appropriately Assess Extreme Liver Resection Techniques.

PMID- 29342017
TI  - Response: "Unresectable Colorectal Liver Metastases: When Definitions Matter to
      Appropriately Assess Extreme Liver Resection Techniques".

PMID- 29342018
TI  - Mini- or Less-open Sublay Operation (MILOS): A New Minimally Invasive Technique
      for the Extraperitoneal Mesh Repair of Incisional Hernias.
AB  - OBJECTIVE: Improvement of ventral hernia repair. BACKGROUND: Despite the use of
      mesh and other recent improvements, the currently popular techniques of ventral
      hernia repair have specific disadvantages and risks. METHODS: We developed the
      endoscopically assisted mini- or less-open sublay (MILOS) concept. The operation
      is performed transhernially via a small incision with light-holding laparoscopic
      instruments either under direct, or endoscopic visualization. An endoscopic light
      tube was developed to facilitate this approach (EndotorchTM Wolf Company). Each
      MILOS operation can be converted to standard total extraperitoneal gas endoscopy
      once an extraperitoneal space of at least 8 cm has been created. All MILOS
      operations were prospectively documented in the German Hernia registry with 1
      year questionnaire follow-up. Propensity score matching of incisional hernia
      operations comparing the results of the MILOS operation with the laparoscopic
      intraperitoneal onlay mesh operation (IPOM) and open sublay repair from other
      German Hernia registry institutions was performed. RESULTS: Six hundred fifteen
      MILOS incisional hernia operations were included. Compared with laparoscopic IPOM
      incisional hernia operation, the MILOS repair is associated with significantly a
      fewer postoperative surgical complications (P < 0.001) general complications (P <
      0.004), recurrences (P < 0.001), and less chronic pain (P < 0.001). Matched pair
      analysis with open sublay repair revealed significantly a fewer postoperative
      complications (P < 0.001), reoperations (P < 0.001), infections (P = 0.007),
      general complications (P < 0.001), recurrences (P = 0.017), and less chronic pain
      (P < 0.001). CONCLUSIONS: The MILOS technique allows minimally invasive
      transhernial repair of incisional hernias using large retromuscular/preperitoneal
      meshes with low morbidity. The technique combines the advantages of open sublay
      and the laparoscopic IPOM repair.ClinicalTrials.gov Identifier NCT03133000.

PMID- 29342019
TI  - Hot Spotting as a Strategy to Identify High-Cost Surgical Populations.
AB  - OBJECTIVE: The aim of this study was to determine the feasibility of "hot
      spotting" in elective surgical populations. BACKGROUND: Prospective
      identification of high-cost patients, known as "hot spotting," is well developed
      in medical populations, but has not been performed in surgical populations.
      Population-based management of surgical expenditures requires identification of
      high-cost surgical patients to allow for effective implementation of cost-saving
      strategies. METHODS: Using 100% Medicare claims data for 2010 to 2013, we
      identified patients aged 65 to 99 years undergoing elective surgical procedures.
      We calculated price-standardized Medicare payments for the surgical episode from
      the index admission through 30 days after discharge. Patient-level factors
      associated with payments were analyzed by multivariable linear regression.
      RESULTS: Medicare patients in the highest decile of spending accounted for a
      disproportionate share of aggregate costs: 30% in Colectomy (COL), 22% in
      coronary artery bypass grafting (CABG), 19% in Total Hip Arthroplasty, and 18% in
      Total Knee Arthroplasty. Medicare expenditure differences between the highest and
      lowest deciles were because of a 5-fold difference for COL and 3-fold difference
      for CABG in index hospitalization cost. In contrast, for orthopedic procedures,
      there were 47- to 80-fold post-acute care expenditures between highest and lowest
      deciles. In multivariable analyses, patients with >=3 comorbidities had
      significantly higher costs than healthier patients. CONCLUSION: We found that a
      subset of multimorbid patients was responsible for a disproportionate share of
      total Medicare spending, but the individual components of spending vary by
      procedure. These findings suggest that targeting high-cost Medicare patients (ie,
      hot spotting) for cost containment efforts would be a potentially effective
      strategy to reduce costs in surgical populations.

PMID- 29342020
TI  - Editorial (Spring) Board? Gender Composition in High-impact General Surgery
      Journals Over 20 Years.
AB  - OBJECTIVE: To quantify gender composition of 10 high-impact general surgery
      journals, delineate how board composition has changed over time, and evaluate
      qualification metrics by gender. BACKGROUND: Underrepresentation of women on
      editorial boards may contribute to the gender-based achievement gap in surgery.
      METHODS: We performed a cross-sectional analysis of the editorial board gender
      composition among 10 high-impact general surgery journals in 1997, 2007, and
      2017. Univariate and multivariate regression analyses were used to assess
      differences in editors' H-indices, academic rank, and number of advanced degrees.
      Differences in editor turnover and multiple board positions were evaluated for
      each time interval. RESULTS: Over 20 years, the proportion of women on editorial
      boards increased from 5% to 19%. After controlling for time since board
      certification, no differences between men and women's number of advances degrees,
      H-indices, or academic rank remained significant. Women and men were equally
      likely to hold multiple board positions (1997 P = 0.74; 2007 P = 0.42; 2017 P =
      0.69), but men's editorial board tenure was longer across each time interval
      (1997-2007 P = 0.003; 2007-2017 P < 0.001; 1997-2017 P = 0.01). CONCLUSIONS:
      Women surgeons have a small but growing presence on surgical editorial boards,
      and gender-based qualification differences are likely attributable to practice
      length. Men's longer tenure on editorial boards may drive some of the observed
      disparity by limiting new appointment opportunities. Strategies such as imposing
      term limits or instituting merit-based performance reviews may help editorial
      boards capture the field's changing demographics.

PMID- 29342021
TI  - Nonoperative Management of Perforated Hollow Viscera in a Palliative Care Unit.

PMID- 29342023
TI  - Physiatry Reviews for Evidence in Practice Second-Order Peer Review: Does Massage
      Therapy Have Value in the Treatment for Tension Type Headache?

PMID- 29342022
TI  - Association Between Altered Hip Extension and Kinetic Gait Variables.
AB  - Kinematic and kinetic outcome measures are tightly linked in walking. Although
      altering motor output is a major goal of gait rehabilitation, little is
      understood regarding the relationship between altering a single kinematic
      variable and kinetic outcome changes. We designed a strategy to isolate hip
      extension alterations during walking on a treadmill to assess the change in
      kinetic outcomes. Ten healthy individuals walked on an instrumented split-belt
      treadmill with motion capture to calculate hip extension and kinetic outcomes at
      the following five different randomized cadences: self-selected cadence, self
      selected +/- 10%, and self-selected +/- 20%. The treadmill speed was held
      constant at the individual's self-selected walking speed, forcing cadence changes
      to result in successful alterations to hip extension, varying 8.3 degrees from
      the self-selected -20% to +20% cadence conditions. Kinetic outcomes demonstrated
      similar alterations. Hip extension changes at each cadence significantly
      correlated with kinetic changes in propulsive impulse (r = 0.852, P < 0.001),
      peak ankle power (r = 0.473, P = 0.002), and ankle plantarflexion work (r =
      0.762, P < 0.001). These results demonstrate that kinetic outcomes are highly
      alterable in response to a kinematic gait change. This clinically relevant
      finding highlights the potential to improve motor output in individuals during
      rehabilitation by altering gait patterns to achieve more optimal limb positions.

PMID- 29342024
TI  - Clinical profile of patients with heart failure can predict rehospitalization and
      quality of life.
AB  - BACKGROUND: The aim of this retrospective study was to identify clinical, humoral
      and echocardiographic variables predicting rehospitalization and poor quality of
      life (QOL) in patients with reduced or mid-range ejection fraction heart failure.
      METHODS: From 2009 to 2012, 310 patients were admitted having signs and symptoms
      of heart failure with reduced ejection fraction. All the patients were followed
      by phone, calling the patients or the referring general practitioner. The
      Minnesota Living with Heart Failure Questionnaire (MLHFQ) was used as the
      instrument to evaluate QOL: MLHFQ less than 24 is a good QOL, 24-45 is moderate
      QOL and more than 45 is poor QOL. The primary event was poor QOL and/or
      rehospitalization at 4 years. RESULTS: Seventy-nine patients died at median time
      of 21 months; 4-year survival was 72 +/- 3%. Rehospitalization due to heart
      failure was recorded in 60 cases. Among 231 survivors, MLHFQ score was good in 99
      (42%), moderate in 50 (21%) and poor in 88 (37%). Four-year freedom from death,
      poor QOL or rehospitalization was 51 +/- 3%. Multivariable analysis identified
      the following risk factors: heart rate at discharge at least 70 bpm, ischemic
      heart disease, atrial fibrillation, hypercholesterolemia, chronic pulmonary
      disease, N-terminal pro brain natriuretic peptide at discharge, severe tricuspid
      regurgitation and mitral regurgitation more than moderate. CONCLUSION: Clinical,
      laboratory and echocardiographic profile is crucial to predict long-term QOL of
      patients admitted for heart failure.

PMID- 29342025
TI  - Pictorial Representation of Joint Involvement in Different Types of
      Spondyloarthropathy.

PMID- 29342026
TI  - Reflections on a life in menopause.

PMID- 29342027
TI  - Response to letter to editor.

PMID- 29342028
TI  - Lymphedema-Distichiasis Syndrome in a Male Patient Followed for 16 Years.
AB  - Distichiasis is a challenging condition that may require multiple surgical
      interventions. Besides ophthalmologic concerns in children, distichiasis may be
      part of the lymphedema-distichiasis syndrome, which presents with lymphedema of
      variable time of onset. Other significant systemic disorders such as coarctation
      of the aorta and varicose veins have been reported in association with this
      syndrome and must be reviewed for proper patient care. The authors report the
      case of a 22-year-old male patient who had been treated for distichiasis and
      followed for 16 years. At his initial evaluation, at 6 years of age, he presented
      solely with ocular complaints due to distichiasis. Only after 13 years of
      repeated ophthalmic treatments and continuous follow up, lymphedema was observed.
      Lymphedema-distichiasis syndrome diagnosis must be considered in children with
      distichiasis, even in the absence of lymphedema.

PMID- 29342029
TI  - Association of Involutional Lower Eyelid Entropion with Reduced Upper Eyelid
      Position Relative to the Corneal Light Reflex: Quantification of Facial
      Asymmetry.
AB  - PURPOSE: To investigate the association between upper eyelid position relative to
      the corneal light reflex (MRD1) and to delineate an association between eyelid
      height and involutional lower eyelid entropion. METHODS: Retrospective study of
      patients presenting for entropion repair to an academic ophthalmic plastic
      surgery service. A total of 111 patients were included in the study; 95 had
      unilateral involutional lower eyelid entropion, and 16 had bilateral lower eyelid
      entropion. Patients with a history of previous eyelid surgery, trauma, upper
      eyelid entropion, or cicatricial changes were excluded from the study. RESULTS:
      Of the 95 patients with unilateral involutional lower eyelid entropion, 45
      (47.4%) had a lesser MRD1 on the side ipsilateral to the involutional lower
      eyelid entropion. In this unilateral group, the mean MRD1 (+/- standard
      deviation) on the ipsilateral to the involutional lower eyelid entropion was 2.9
      (+/-1.2) mm, while the mean MRD1 on the contralateral side was 3.3 (+/-1.0) mm.
      This difference was 0.4 mm and was statistically significant (p < 0.0001). Most
      patients with unilateral involutional entropion demonstrated a right-sided
      involutional lower eyelid entropion (56 of 95; 58.9%), although this finding was
      not statistically significant (p = 0.083). The frequency of true blepharoptosis
      (MRD1 <= 2.0 mm) was 24 of 95 (25.3%) in the unilateral involutional entropion
      group and was even higher in the bilateral involutional lower eyelid entropion
      group, with 7 of 16 (43.8%) patients exhibiting bilateral blepharoptosis.
      CONCLUSIONS: Patients presenting with involutional lower eyelid entropion tend to
      have a relatively reduced MRD1 on the ipsilateral (affected) side. When both
      lower eyelids are affected by involutional entropion, the reduced MRD1 tends to
      be more pronounced.

PMID- 29342030
TI  - Mesenchymal Chondrosarcoma of the Lacrimal Gland.
AB  - A 23-year-old woman presented with right-sided painless proptosis that developed
      in 12 months. MRI studies demonstrated a well-delineated tumorous enlargement of
      the right lacrimal gland with homogenous signal intensity and compressing the
      globe. The tumor was removed totally and in 1 piece with the tentative diagnosis
      of a pleomorphic adenoma. Pathologic examination revealed biphasic neoplastic
      elements, which were composed of the cartilaginous matrix and small round cell
      component. Immunohistopathological examination showed positive CD99 staining and
      negative reaction to S100, panCK, and CD15. The patient then received a total of
      64 Gy orbital radiotherapy in 32 fractionations. There has been no recurrence or
      metastasis during 14 months of follow up. This case showed that mesenchymal
      chondrosarcoma may arise from the lacrimal gland and must be considered in the
      differential diagnosis of lacrimal gland tumors in young adults.

PMID- 29342031
TI  - Adenocarcinoma of Pigmented Ciliary Epithelium in a Child With Aicardi Syndrome
      and Congenital Microphthalmia With Cyst.
AB  - A 5-year-old girl with Aicardi syndrome and microphthalmia with cyst of the OD
      presented with progressive enlargement of the cyst causing pain. Microophthalmia
      with inferior cyst (35 * 25 * 12 mm) was noted at birth, and Aicardi syndrome was
      diagnosed at 10 months by the presence of the classic triad of callosal agenesis,
      infantile spasms, and chorioretinal lacunae. She underwent enucleation with cyst
      resection, and subsequent reconstruction with a dermis fat graft. Histopathologic
      study revealed adenocarcinoma of the pigmented ciliary epithelium. Full-body
      metastatic workup was negative. Adenocarcinoma of the pigmented ciliary
      epithelium is an extremely rare eye tumor with only 4 documented cases in the
      literature, none arising in a microophthalmic eye with cyst. Aicardi syndrome is
      also a rare disease that has been associated with increased incidence of
      malignancy and ocular abnormalities, but has never been described in association
      with microophthalmia with cyst or with adenocarcinoma of the pigmented ciliary
      epithelium. Herein, the authors present a review of the case and relevant
      literature.

PMID- 29342032
TI  - Angiomatosis of the Orbit: Clinical, Imaging, and Histologic Findings.
AB  - Angiomatosis is a complex vascular malformation that denotes a clinically
      extensive hemangioma, which either involves multiple tissue planes or extensively
      infiltrates 1 type of tissue. It is a rare condition characterized by diffuse
      proliferation of blood vessels admixed with fat and fibrotic tissue. Typically,
      this process involves the limbs in multiple tissue planes, including dermis,
      subcutis, muscle, and bone. In this report, the authors present the first case of
      angiomatosis infiltrating the orbit, controlled effectively with a combination of
      systemic steroids, radiation, and beta-blocker therapy. The characteristic
      imaging and histologic features and management options are discussed.

PMID- 29342033
TI  - Meningoencephalocele and Cerebrospinal Fluid Leak Complicating Orbital
      Decompression.
AB  - A 51-year-old man who had undergone right orbital decompression 5 months earlier
      developed a meningoencephalocele extending in the right sphenoid sinus through a
      skull base defect of the right ethmoid, sphenoid, and frontal bones. The authors
      report the third case to their knowledge of meningoencephalocele with
      cerebrospinal fluid leak after orbital decompression and discuss its management
      and measures that can be taken to prevent this rare but serious complication.

PMID- 29342034
TI  - Atypical Presentation of Squamous Papilloma.

PMID- 29342036
TI  - Trends in Intraoperative Testing During Cochlear Implantation.
AB  - OBJECTIVE: No consensus guidelines exist regarding intraoperative testing during
      cochlear implantation and wide variation in practice habits exists. The objective
      of this observational study was to survey otologists/neurotologists to understand
      practice habits and overall opinion of usefulness of intraoperative testing.
      STUDY DESIGN: Cross-sectional survey. SETTING: A web-based survey was sent to 194
      practicing Otologists/Neurotologists. MAIN OUTCOME MEASURES: Questions included
      practice setting and experience, habits with respect to electrodes used,
      intraoperative testing modalities used, overall opinion of intraoperative
      testing, and practice habits in various scenarios. RESULTS: Thirty-nine of 194
      (20%) completed the survey. For routine patients, ECAPs and EIs were most
      commonly used together (38%) while 33% do not perform testing at all. Eighty-nine
      percent note that testing "rarely" or "never" changes management. Fifty-one
      percent marked the most important reason for testing is the reassurance provided
      to the family and/or the surgeon. CONCLUSION: Intraoperative testing habits and
      opinions regarding testing during cochlear implantation vary widely among
      otologic surgeons. The majority of surgeons use testing but many think there is
      minimal benefit and that surgical decision-making is rarely impacted. The
      importance of testing may change as electrodes continue to evolve.

PMID- 29342035
TI  - Systematic Review of Hearing Preservation After Radiotherapy for Vestibular
      Schwannoma.
AB  - OBJECTIVE: To determine the long-term hearing preservation rate for spontaneous
      vestibular schwannoma treated by primary radiotherapy. DATA SOURCES: The
      MEDLINE/PubMed, Web of Science, Cochrane Reviews, and EMBASE databases were
      searched using a comprehensive Boolean keyword search developed in conjunction
      with a scientific librarian. English language papers published from 2000 to 2016
      were evaluated. STUDY SELECTION: Inclusion criteria: full articles, pretreatment
      and posttreatment audiograms or audiogram based scoring system, vestibular
      schwannoma only tumor type, reported time to follow-up, published after 1999, use
      of either Gamma Knife or linear accelerator radiotherapy. EXCLUSION CRITERIA:
      case report or series with fewer than five cases, inadequate audiometric data,
      inadequate time to follow-up, neurofibromatosis type 2 exceeding 10% of study
      population, previous treatment exceeding 10% of study population, repeat
      datasets, use of proton beam therapy, and non-English language. DATA EXTRACTION:
      Two reviewers independently analyzed papers for inclusion. Class A/B, 1/2 hearing
      was defined as either pure tone average less than or equal to 50 db with speech
      discrimination score more than or equal to 50%, American Academy of
      Otolaryngology-Head & Neck Surgery (AAO-HNS) Hearing Class A or B, or Gardner
      Robertson Grade I or II. Aggregate data were used when individual data were not
      specified. DATA SYNTHESIS: Means were compared with student t test. CONCLUSIONS:
      Forty seven articles containing a total of 2,195 patients with preserved Class
      A/B, 1/2 hearing were identified for analysis. The aggregate crude hearing
      preservation rate was 58% at an average reporting time of 46.6 months after
      radiotherapy treatment. Analysis of time-based reporting shows a clear trend of
      decreased hearing preservation extending to 10-year follow-up. This data
      encourages a future long-term controlled trial.

PMID- 29342037
TI  - Preservation of Cells of the Organ of Corti and Innervating Dendritic Processes
      Following Cochlear Implantation in the Human: An Immunohistochemical Study.
AB  - HYPOTHESIS: This study evaluates the degree of preservation of hair cells,
      supporting cells, and innervating dendritic processes after cochlear implantation
      in the human using immunohistochemical methods. BACKGROUND: Surgical insertion of
      a cochlear implant electrode induces various pathologic changes within the
      cochlea including insertional trauma, foreign body response, inflammation,
      fibrosis, and neo-osteogenesis. These changes may result in loss of residual
      acoustic hearing, adversely affecting the use of hybrid implants, and may result
      in loss of putative precursor cells, limiting the success of future regenerative
      protocols. METHODS: Twenty-eight celloidin-embedded temporal bones from 14
      patients with bilateral severe to profound sensorineural hearing loss and
      unilateral cochlear implants were studied. Two sections including the modiolus or
      basal turn from each temporal bone were stained using antineurofilament,
      antimyosin-VIIa, and antitubulin antibodies in both the implanted and unimplanted
      ears. RESULTS: Inner and outer hair cells: Immunoreactivity was reduced
      throughout the implanted cochlea and in the unimplanted cochlea with the
      exception of the apical turn.Dendritic processes in the osseous spiral lamina:
      Immunoreactivity was significantly less along the electrode of the implanted
      cochlea than in the other segments.Inner and outer pillars, inner and outer
      spiral bundles, and Deiters' cells: Immunoreactivity was similar in the implanted
      and unimplanted cochleae. CONCLUSION: Insertion of a cochlear implant electrode
      may significantly affect the inner and outer hair cells both along and apical to
      the electrode, and dendritic processes in the osseous spiral lamina along the
      electrode. There was less effect on pillar cells, Deiters' cells, and spiral
      bundles.

PMID- 29342038
TI  - Utility of Noncontrast Magnetic Resonance Imaging for Detection of Recurrent
      Vestibular Schwannoma.
AB  - BACKGROUND: Gadolinium-enhanced T1-weighted magnetic resonance imaging (MRI)
      (T1WI) is the conventional imaging technique of choice to detect vestibular
      schwannoma (VS) recurrence or regrowth, despite suboptimal specificity secondary
      to enhancing postoperative changes. Furthermore, recent concerns regarding the
      accumulation of gadolinium in body tissues have led for a call to reduce the
      number of contrast-enhanced examinations. The objective of the current study is
      to evaluate the diagnostic accuracy of high-resolution noncontrast (three
      dimensional [3D] T2) MRI relative to gadolinium-enhanced T1WI in the detection of
      VS recurrence after resection. METHODS: Following Institutional Review Board
      approval, 13 consecutive postoperative patients with VS recurrence or regrowth
      were identified from a prospectively maintained clinical database in which
      recurrence was determined by progression on serial postoperative MRI examination.
      Three blinded neuroradiologists retrospectively evaluated a total of 41
      postoperative MRI examinations from these patients using only gadolinium-enhanced
      T1WI and 3D T2 MRI for recurrence or regrowth. Interobserver agreement,
      differences in detection between the two sequences, and the sensitivity and
      specificity of 3D T2 MRI were assessed. RESULTS: Fifteen of the 41 postoperative
      MRIs demonstrated progression, as determined by examiner consensus on the
      gadolinium-enhanced T1WI. Agreement, measured using Krippendorff's alpha, was
      0.82 for the 3D T2 images and 0.83 for the contrast-enhanced T1WI. All the three
      examiners demonstrated no difference in the detection of progression between the
      two sequences (McNemar's test p values 0.69 for examiner 1, 0.63 for examiner 2,
      and 0.99 for examiner 3). The sensitivity of 3D T2 was 0.78 (CI 0.60-0.96), while
      the specificity was 0.94 (CI 0.86-1.00). CONCLUSION: Noncontrast high-resolution
      3D T2 MRI seems sufficient to assess for recurrence or regrowth after VS
      resection. The results of this study have implications for reducing cost, time,
      and adverse events associated with gadolinium administration in this population
      requiring serial follow-up examinations. These promising, yet preliminary
      findings warrant confirmation with a larger prospective cohort of patients.

PMID- 29342039
TI  - An Optimal Partial Ossicular Prosthesis Should Connect Both to the Tympanic
      Membrane and Malleus: A Temporal Bone Study Using Laser Doppler Vibrometry.
AB  - OBJECTIVE: To compare stapes vibrations in different partial ossicular
      replacement prosthesis (PORP) applications. METHODS: Stapedial vibrations were
      measured on fresh frozen human temporal bones with laser Doppler vibrometry.
      Eight different types of common ossiculoplasty methods were compared regarding
      recovery of stapes vibrations in relation with the normal ossicular chain. The
      PORPs were divided into three groups: 1) PORPs with the lateral contact only with
      the tympanic membrane, 2) PORPs with lateral contact only to the malleus handle,
      and 3) PORPs with lateral contact with both the malleus handle and the tympanic
      membrane. RESULTS: The PORPs with lateral contact only to the malleus handle
      performed better than the PORPs with lateral contact to the tympanic membrane
      only at 2 kHZ, but the best recovery was found in the group with contact both to
      the malleus handle and the tympanic membrane. CONCLUSION: The best sound
      transmission might be achieved by placing a PORP in contact with both the
      tympanic membrane and the handle of the malleus.

PMID- 29342040
TI  - Unilateral Sensorineural Hearing Loss Presenting With Bilateral Temporal Bone
      Lesions.

PMID- 29342041
TI  - History of the Research Fund of the American Otological Society.

PMID- 29342043
TI  - The American Otological Society at its Sesquicentennial: Insights Into the
      Society's Formative Years.
AB  - OBJECTIVE: To elucidate the sequence of events which led to the formation of the
      American Otological Society (AOS) in 1868 and to examine the lives and
      contributions of the nine founding members of the Society. METHODS: Study of
      primary historical documents, biographical material, and previous histories of
      the AOS. RESULTS: Earlier treatments of the history of the AOS minimally covered
      the events and personalities from the Society's formative period. The founders of
      the AOS were much influenced by recent advances in European Otology and the
      success of the nascent American Ophthalmological Society which had been founded
      in 1864. The AOS has long credited Elkanah Williams as its first president of the
      AOS, although he never actually served in this role and was not a contributor to
      otological literature. Documents suggest that 30 years old New York physician
      Daniel Bennett St John Roosa, recently returned from a grand tour of the leading
      European otological centers, was the principal advocate for the creation of the
      AOS. CONCLUSIONS: The 1860s were a pivotal period in the maturation of American
      Otology. Previously, most "aurists" were widely considered to be charlatans who
      practiced unscientifically and often unscrupulously. The AOS founder generation
      were a group of Ophthalmologists who strove to elevate otology from being a
      lesser appendage of the mother field to becoming a respected and scientifically
      based medical specialty in its own right.

PMID- 29342042
TI  - Long-term Administration of Salicylate-induced Changes in BDNF Expression and
      CREB Phosphorylation in the Auditory Cortex of Rats.
AB  - HYPOTHESIS: We investigated whether salicylate induces tinnitus through
      alteration of the expression levels of brain-derived neurotrophic factor (BDNF),
      proBDNF, tyrosine kinase receptor B (TrkB), cAMP-responsive element-binding
      protein (CREB), and phosphorylated CREB (p-CREB) in the auditory cortex (AC).
      BACKGROUND: Salicylate medication is frequently used for long-term treatment in
      clinical settings, but it may cause reversible tinnitus. Salicylate-induced
      tinnitus is associated with changes related to central auditory neuroplasticity.
      Our previous studies revealed enhanced neural activity and ultrastructural
      synaptic changes in the central auditory system after long-term salicylate
      administration. However, the underlying mechanisms remained unclear. METHODS:
      Salicylate-induced tinnitus-like behavior in rats was confirmed using gap
      prepulse inhibition of acoustic startle and prepulse inhibition testing, followed
      by comparison of the expression levels of BDNF, proBDNF, TrkB, CREB, and p-CREB.
      Synaptic ultrastructure was observed under a transmission electron microscope.
      RESULTS: BDNF and p-CREB were upregulated along with ultrastructural changes at
      the synapses in the AC of rats treated chronically with salicylate (p < 0.05,
      compared with control group). These changes returned to normal after 14 days of
      recovery (p > 0.05). CONCLUSION: Long-term administration of salicylate increased
      BDNF expression and CREB activation, upregulated synaptic efficacy, and changed
      synaptic ultrastructure in the AC. There may be a relationship between these
      factors and the mechanism of tinnitus.

PMID- 29342045
TI  - Jugular Foramen Meningioma.

PMID- 29342044
TI  - Elevated Level of Myeloperoxidase-Deoxyribonucleic Acid Complex in the Middle Ear
      Fluid Obtained From Patients With Otitis Media Associated With Antineutrophil
      Cytoplasmic Antibody-associated Vasculitis.
AB  - OBJECTIVE: The purpose was to explore the presence of myeloperoxidase (MPO)
      deoxyribonucleic acid (DNA) complex as a surrogate marker of neutrophil
      extracellular traps (NETs) in the middle ear fluid, and to clarify the
      correlation between its quantifiable level and hearing outcome in patients with
      otitis media associated with antineutrophil cytoplasmic antibody (ANCA)
      associated vasculitis (AAV). STUDY DESIGN: Prospective study. SETTING: Tertiary
      referral center. PATIENTS: Nine AAV patients presenting with otitis media.
      INTERVENTION: Collection of the fluid samples from middle ear. MAIN OUTCOME
      MEASURE: The quantifiable levels of MPO-DNA complex using an enzyme-linked
      immunosorbent assay. RESULTS: The quantifiable levels of MPO-DNA complex in
      patients with AAV were significantly higher than those in controls (p < 0.001).
      In particular, both ANCA-positive and -negative cases indicated higher levels of
      MPO-DNA complex compared with the controls (p = 0.004 and p = 0.006,
      respectively). The significant negative correlations were observed between the
      level of MPO-DNA complex and the functional hearing values for air (r = -0.82, p
      = 0.009) and bone conduction (r = -0.73, p = 0.028), respectively. CONCLUSION:
      This analysis is the first to reveal the presence of elevated levels of MPO-DNA
      complex in the middle ear fluid, suggesting the pathogenic role of NETs in otitis
      media associated with AAV. NETs may be a valuable biomarker for use in clinical
      decision-making and predicting hearing outcome, regardless of ANCA status.

PMID- 29342046
TI  - Large Facial Nerve Schwannoma With Extensive Temporal Bone Destruction.

PMID- 29342047
TI  - Direction-fixed and Direction-changing Positional Nystagmus in Ramsay Hunt
      Syndrome.
AB  - OBJECTIVES: To investigate the incidence of positional nystagmus (PN) using a
      head-roll test in patients with Ramsay Hunt syndrome with vertigo (RHS_V) and
      discuss possible mechanisms. STUDY DESIGN: Retrospective study. SETTING: Tertiary
      referral academic medical center. PATIENTS: Twenty-eight patients with RHS_V were
      enrolled. MAIN OUTCOME MEASURE: Eye movements were recorded at positions of head
      roll to the right or left, and PN was classified as direction-fixed or direction
      changing. Vestibular function tests including caloric test were performed.
      RESULTS: Direction-fixed nystagmus beating away from the affected side was the
      most common type of PN (61%), followed by direction-changing geotropic type
      (18%), direction-fixed nystagmus beating toward the affected side (14%), and
      direction-changing apogeotropic type (7%). The duration of nystagmus was longer
      than 60 seconds in all patients exhibiting direction-changing PN. Postcontrast T1
      weighted internal auditory canal (IAC) magnetic resonance imaging showed
      enhancement of not only the facial and vestibulocochlear nerves, but also the
      inner ear structures or dura along the IAC, suggesting inflammatory changes
      within the labyrinthine membrane or IAC dura. CONCLUSION: Although direction
      fixed PN was more commonly observed (75%), direction-changing PN was also
      observed in some RHS_V patients (25%). The mechanism of direction-changing PN may
      be, at least in part, explained by the alteration of specific gravity of the
      lateral semicircular canal cupula or endolymph due to inflammation in the inner
      ear membrane.

PMID- 29342048
TI  - External Ear Arteriovenous Malformation.

PMID- 29342049
TI  - The Impact of the Transcanal Endoscopic Approach and Mastoid Preservation on
      Recurrence of Primary Acquired Attic Cholesteatoma.
AB  - OBJECTIVE: We aim to investigate the factors associated with recurrent disease
      following surgery for primary acquired attic cholesteatoma. We hypothesize that
      minimal invasive, mucosal sparing operation techniques have beneficial effects on
      the outcome in terms of recurrence. STUDY DESIGN: Retrospective study. SETTING:
      Tertiary referral center. PARTICIPANTS: A total of 110 patients presenting with
      primary acquired attic cholesteatoma were enrolled in the study. Patients
      undergoing revision surgery or a canal wall down procedure, as well as patients
      with residual disease were excluded from the study. MAIN OUTCOME MEASURES: During
      follow-up recurrence was assessed and classified into normal, self-cleaning
      retraction pockets, or recurrent cholesteatoma requiring revision surgery.
      RESULTS: We observed during follow-up statistically significant decrease (p =
      0.036) in the occurrence of retraction pockets and recurrence in patients
      operated by the transcanal endoscopic approach (n = 55, 11% re-retraction, 9%
      recurrence) compared with those who underwent a canal wall up procedure (n = 55,
      16% re-retraction, 22% recurrence). However, the multivariate model did not
      demonstrate statistically significant predictors regarding the outcome. Moreover,
      the preservation or direct reconstruction of the ossicular chain had a beneficial
      effect on the outcome. We observed 11% re-retraction and 9% recurrence in cases
      with preserved or reconstructed ossicular chain versus 18% re-retraction and 24%
      recurrence (p = 0.011) in cases of nonpreserved or non-reconstructed ossicular
      chain. A score was established according to the intraoperative mucosal damage and
      correlated to the occurrence of recurrence (p = 0.02). The risk of recurrence
      increased by 23.6% (95% confidence interval: 3.22-48.1) with each additional
      mucosal damage site. CONCLUSION: Transcanal endoscopic approaches that preserve
      the mastoid may play an important role in preventing recurrence and underscores
      the importance of the mucosa and mastoid air cells on middle ear homeostasis.

PMID- 29342050
TI  - Intraoperative Cochlear Implant Device Testing Utilizing an Automated Remote
      System: A Prospective Pilot Study.
AB  - INTRODUCTION: Intraoperative cochlear implant device testing provides valuable
      information regarding device integrity, electrode position, and may assist with
      determining initial stimulation settings. Manual intraoperative device testing
      during cochlear implantation requires the time and expertise of a trained
      audiologist. The purpose of the current study is to investigate the feasibility
      of using automated remote intraoperative cochlear implant reverse telemetry
      testing as an alternative to standard testing. METHODS: Prospective pilot study
      evaluating intraoperative remote automated impedance and Automatic Neural
      Response Telemetry (AutoNRT) testing in 34 consecutive cochlear implant surgeries
      using the Intraoperative Remote Assistant (Cochlear Nucleus CR120). In all cases,
      remote intraoperative device testing was performed by trained operating room
      staff. A comparison was made to the "gold standard" of manual testing by an
      experienced cochlear implant audiologist. Electrode position and absence of tip
      fold-over was confirmed using plain film x-ray. RESULTS: Automated remote reverse
      telemetry testing was successfully completed in all patients. Intraoperative x
      ray demonstrated normal electrode position without tip fold-over. Average
      impedance values were significantly higher using standard testing versus CR120
      remote testing (standard mean 10.7 kOmega, SD 1.2 vs. CR120 mean 7.5 kOmega, SD
      0.7, p < 0.001). There was strong agreement between standard manual testing and
      remote automated testing with regard to the presence of open or short circuits
      along the array. There were, however, two cases in which standard testing
      identified an open circuit, when CR120 testing showed the circuit to be closed.
      Neural responses were successfully obtained in all patients using both systems.
      There was no difference in basal electrode responses (standard mean 195.0 MUV, SD
      14.10 vs. CR120 194.5 MUV, SD 14.23; p = 0.7814); however, more favorable (lower
      MUV amplitude) results were obtained with the remote automated system in the
      apical 10 electrodes (standard 185.4 MUV, SD 11.69 vs. CR120 177.0 MUV, SD 11.57;
      p value < 0.001). CONCLUSION: These preliminary data demonstrate that
      intraoperative cochlear implant device testing using a remote automated system is
      feasible. This system may be useful for cochlear implant programs with limited
      audiology support or for programs looking to streamline intraoperative device
      testing protocols. Future studies with larger patient enrollment are required to
      validate these promising, but preliminary, findings.

PMID- 29342052
TI  - Preauricular Approach for Cholesteatoma Resection After Surgical Overclosure of
      the External Auditory Canal and Cochlear Implantation.
AB  - : Chronic suppurative otitis media can have long-term effects on hearing if not
      managed effectively. When combined with cholesteatoma the condition may require
      creation of an open mastoid cavity. Recurrence of cholesteatoma is a concern when
      cochlear implantation is performed with overclosure of the external auditory
      meatus. A 61-year-old female with recurrent cholesteatoma in this setting was
      treated using a preauricular approach to provide adequate visualization while
      preventing the need to remove the implant or risking injury to the internal
      components. This technique would be useful in similar patients to prevent
      morbidity from removal and reinsertion of a cochlear implant.

PMID- 29342051
TI  - Does Hospital Volume Affect Outcomes in Patients Undergoing Vestibular Schwannoma
      Surgery?
AB  - OBJECTIVE: To determine the effect of hospital surgical case volume on the
      outcomes of vestibular schwannoma surgery. STUDY DESIGN: Retrospective case
      review. SETTING: University HealthSystem Consortium member hospitals (includes
      nearly every US academic medical center). PATIENTS: Three thousand six hundred
      ninety-seven patients who underwent vestibular schwannoma resection over a 3-year
      timespan (2012-2015) grouped by race, age, comorbidities, payer, and sex.
      INTERVENTION: Surgical resection of vestibular schwannoma. MAIN OUTCOME MEASURES:
      Morbidity and mortality following vestibular schwannoma excision are compared by
      hospital volume (low, medium, and high) including deciles. RESULTS: There was
      significantly longer length of stay (p <= 0.005) among groups with low-volume
      hospitals followed by medium-volume hospitals and high-volume hospitals. Low
      volume hospitals had a significantly higher rate of complications including
      stroke, aspiration, and respiratory failure (p <= 0.0175). Patient
      characteristics of age, sex, sex, and baseline comorbidities were similar between
      hospital groups. However, patients at high-volume hospitals were more likely to
      be Caucasian (83.1%, p = 0.0001) and have private insurance (76.7%, p < 0.0001).
      There was a strong negative correlation between complication rates and hospital
      volume (r = -0.8164, p = 0.0040). CONCLUSION: The volume of vestibular schwannoma
      surgeries performed at a hospital impacts length of stay and rates of
      postoperative complications. Demographics among hospital groups were similar
      though high-volume hospitals had significantly more patients who were privately
      insured and Caucasian.

PMID- 29342053
TI  - Gradual Symmetric Progression of DFNA34 Hearing Loss Caused by an NLRP3 Mutation
      and Cochlear Autoinflammation.
AB  - OBJECTIVE: To characterize the audiometric phenotype of autosomal-dominant DFNA34
      hearing loss (HL) caused by a missense substitution in the NLRP3 gene. NLRP3
      encodes a critical component of the NLRP3 inflammasome that is activated in
      innate immune responses. STUDY DESIGN: This study was conducted under protocol 01
      DC-0229 approved by the NIH Combined Neurosciences IRB. We performed medical and
      developmental history interviews and physical and audiological examinations of
      affected individuals with DFNA34 HL caused by the p.Arg918Gln mutation of NLRP3.
      We retrospectively reviewed audiological reports, when available, from other
      health care centers. SETTING: Federal biomedical research facility. SUBJECTS:
      Eleven members of a North American family segregating p.Arg918Gln. MAIN OUTCOME
      MEASURES: Pure-tone thresholds, rates of pure-tone threshold progression, and
      speech discrimination scores. RESULTS: Eight subjects had bilateral sensorineural
      HL with an onset in the late 2nd to 4th decade of life. Slowly progressive HL
      initially primarily affected high frequencies. Low and middle frequencies were
      affected with advancing age, resulting in moderate HL with a downsloping
      audiometric configuration. The average annual threshold deterioration was 0.9 to
      1.5 dB/yr. Speech recognition scores ranging from 60 to 100% were consistent with
      cochlear, but not retrocochlear, etiology. Three subjects (16, 22, and 32 yr old)
      had normal hearing thresholds. CONCLUSION: DFNA34 HL has an onset during early
      adulthood and progresses approximately 1.2 dB/yr.

PMID- 29342055
TI  - Benefit of Preoperative Temporal Bone CT for Atraumatic Cochlear Implantation.
AB  - HYPOTHESIS: Evaluate the benefit of preoperative surgical planning using computed
      tomography (CT) for atraumatic cochlear implantation. BACKGROUND: The surgical
      technique has a direct impact on hearing and structure preservation. Much
      interest has been given to depth of electrode insertion. We focused on electrode
      diameter depending on exposure of round window membrane (RWM) as calculated on
      preoperative CT. METHODS: Measurements were calculated radiologically and
      anatomically on 10 temporal bones. Results were compared with CT scans of a
      control population. Thereafter, preoperative CT scan measurements were applied to
      seven additional temporal bones that underwent cochlear implantation with the
      insertion of two electrodes of different diameters (14 implantations) to validate
      radiological analysis. RESULTS: RWM size was 1.5 +/- 0.2 mm on CT and 1.2 +/- 0.2
      mm during dissection; posterosuperior bony overhang of round window niche was 1.1
      +/- 0.1 mm on CT and 1.3 +/- 0.2 mm during dissection. There was no statistically
      significant difference between radiological and anatomical measurements and
      between radiological measurements of cadaveric temporal bones and control
      population (p > 0.05 for both). Also, preoperative surgical planning was reliable
      in the seven temporal bones implanted with two electrode types (accuracy 93%,
      sensitivity 85.7%, specificity 100%) yielding no damage to intracochlear
      structures. CONCLUSION: Difficulties to access RWM could be predicted on
      preoperative CT of temporal bones and control population, which correlated well
      with anatomical dissections and surgical findings during cochlear implantation.
      According to CT planning, electrode insertion through RWM was feasible in most
      patients, with or without drilling posterosuperior bony overhang of round window
      niche. Promontory cochleostomy could be recommended when electrode apical
      diameter exceeded maximal RWM exposure. There was no case of intracochlear trauma
      on microdissections.

PMID- 29342054
TI  - Multicenter US Clinical Trial With an Electric-Acoustic Stimulation (EAS) System
      in Adults: Final Outcomes.
AB  - OBJECTIVE: To demonstrate the safety and effectiveness of the MED-EL Electric
      Acoustic Stimulation (EAS) System, for adults with residual low-frequency hearing
      and severe-to-profound hearing loss in the mid to high frequencies. STUDY DESIGN:
      Prospective, repeated measures. SETTING: Multicenter, hospital. PATIENTS: Seventy
      three subjects implanted with PULSAR or SONATA cochlear implants with FLEX
      electrode arrays. INTERVENTION: Subjects were fit postoperatively with an audio
      processor, combining electric stimulation and acoustic amplification. MAIN
      OUTCOME MEASURES: Unaided thresholds were measured preoperatively and at 3, 6,
      and 12 months postactivation. Speech perception was assessed at these intervals
      using City University of New York sentences in noise and consonant-nucleus
      consonant words in quiet. Subjective benefit was assessed at these intervals via
      the Abbreviated Profile of Hearing Aid Benefit and Hearing Device Satisfaction
      Scale questionnaires. RESULTS: Sixty-seven of 73 subjects (92%) completed outcome
      measures for all study intervals. Of those 67 subjects, 79% experienced less than
      a 30 dB HL low-frequency pure-tone average (250-1000 Hz) shift, and 97% were able
      to use the acoustic unit at 12 months postactivation. In the EAS condition, 94%
      of subjects performed similarly to or better than their preoperative performance
      on City University of New York sentences in noise at 12 months postactivation,
      with 85% demonstrating improvement. Ninety-seven percent of subjects performed
      similarly or better on consonant-nucleus-consonant words in quiet, with 84%
      demonstrating improvement. CONCLUSION: The MED-EL EAS System is a safe and
      effective treatment option for adults with normal hearing to moderate
      sensorineural hearing loss in the low frequencies and severe-to-profound
      sensorineural hearing loss in the high frequencies who do not benefit from
      traditional amplification.

PMID- 29342056
TI  - "Product" Versus "Process" Measures in Assessing Speech Recognition Outcomes in
      Adults With Cochlear Implants.
AB  - HYPOTHESES: 1) When controlling for age in postlingual adult cochlear implant
      (CI) users, information-processing functions, as assessed using "process"
      measures of working memory capacity, inhibitory control, information-processing
      speed, and fluid reasoning, will predict traditional "product" outcome measures
      of speech recognition. 2) Demographic/audiologic factors, particularly duration
      of deafness, duration of CI use, degree of residual hearing, and socioeconomic
      status, will impact performance on underlying information-processing functions,
      as assessed using process measures. BACKGROUND: Clinicians and researchers rely
      heavily on endpoint product measures of accuracy in speech recognition to gauge
      patient outcomes postoperatively. However, these measures are primarily
      descriptive and were not designed to assess the underlying core information
      processing operations that are used during speech recognition. In contrast,
      process measures reflect the integrity of elementary core subprocesses that are
      operative during behavioral tests using complex speech signals. METHODS: Forty
      two experienced adult CI users were tested using three product measures of speech
      recognition, along with four process measures of working memory capacity,
      inhibitory control, speed of lexical/phonological access, and nonverbal fluid
      reasoning. Demographic and audiologic factors were also assessed. RESULTS: Scores
      on product measures were associated with core process measures of speed of
      lexical/phonological access and nonverbal fluid reasoning. After controlling for
      participant age, demographic and audiologic factors did not correlate with
      process measure scores. CONCLUSION: Findings provide support for the important
      foundational roles of information processing operations in speech recognition
      outcomes of postlingually deaf patients who have received CIs.

PMID- 29342058
TI  - MRI Evaluation of Repaired Versus Unrepaired Interportal Capsulotomy in
      Simultaneous Bilateral Hip Arthroscopy: A Double-Blind, Randomized Controlled
      Trial.
AB  - BACKGROUND: Techniques used in hip arthroscopy continue to evolve, and
      controversy surrounds the need for capsular repair following this surgical
      intervention. The purpose of this study was to evaluate the magnetic resonance
      imaging (MRI) appearance of the hip capsule in patients with femoroacetabular
      impingement (FAI) who underwent simultaneous bilateral hip arthroscopy through an
      interportal capsulotomy with each hip randomized to undergo capsular repair or
      not undergo such a repair. METHODS: This double-blind, randomized controlled
      trial included 15 patients (30 hips), with a mean age of 29.2 years, who
      underwent simultaneous bilateral hip arthroscopy utilizing a small (<3-cm)
      interportal capsulotomy for the treatment of FAI. The first hip treated in each
      patient was intraoperatively randomized to undergo capsular repair or no capsular
      repair. The contralateral hip then received the opposite treatment. MRI was
      performed at 6 and 24 weeks postoperatively, and the scans were analyzed by 2
      musculoskeletal radiologists. The patients and the radiologists were blinded to
      the treatment performed on each hip. Capsular dimensions were measured at the
      level of the healing capsulotomy site and, for hips with a persistent defect, at
      locations both proximal and distal to the defect. These values were then analyzed
      at both time points to assess the rate and extent of capsular healing. RESULTS:
      At 6 weeks postoperatively, a continuous hip capsule (with no apparent
      capsulotomy defect) was observed in 8 hips treated with capsular repair and 3
      hips without such a repair. Of the 19 hips with a discontinuous capsule at 6
      weeks, 17 were available for follow-up at 24 weeks postoperatively; all 17
      demonstrated progression to healing, with a contiguous appearance without defects
      and no difference in capsular dimensions between treatment cohorts. CONCLUSIONS:
      Arthroscopic repair of a small interportal hip capsulotomy site yields an
      insignificant increase in the percentage of continuous hip capsules seen on MRI
      at 6 weeks postoperatively compared with no repair. Repaired and unrepaired
      capsulotomy sites progressed to healing with a contiguous appearance on MRI by 24
      weeks postoperatively. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions
      for Authors for a complete description of levels of evidence.

PMID- 29342057
TI  - Audiologic Natural History of Small Volume Cochleovestibular Schwannomas in
      Neurofibromatosis Type 2.
AB  - OBJECTIVE: To characterize the audiometric natural progression in patient-ears
      with small volume (<1,000 mm), treatment-naive cochleovestibular schwannomas
      (CVSs) in Neurofibromatosis Type 2 (NF2). STUDY DESIGN: Prospective, longitudinal
      cohort study. SETTING: Quaternary medical research institute. PATIENTS: One
      hundred eleven ears in 71 NF2 patients with small, treatment-naive CVSs observed
      from July 2006 to July 2016. INTERVENTION: Serial audiometric testing, including
      pure tone audiometry, speech audiometry, and magnetic resonance imaging (MRI).
      OUTCOME MEASURES: Four-frequency pure tone average (4f-PTA) of 0.5, 1, 2, and 4
      kHz and word recognition score (WRS) were recorded. Their changes were compared
      with MRI changes in CVS volume over time. Times to significant hearing loss (10
      dB loss in 4f-PTA) and WRS based on 95% critical difference were measured.
      RESULTS: Linear regression analysis showed a significant correlation with
      baseline hearing level (4f-PTA) and internal auditory canal (IAC) tumor volume to
      annual hearing decrease rate (AHDR) (p = 0.003, p = 0.0004). Hearing level at
      baseline and tumor volume correlate with AHDR while tumor volume growth rate does
      not. Two-way analysis of variance found significant differences in AHDR, risk of
      significant hearing loss, and risk of critical difference in WRS based on
      baseline hearing level (abnormal or normal) and IAC tumor volume (greater or less
      than 200 mm). CONCLUSION: Subjects with normal baseline hearing and small IAC
      tumor component had a low AHDR and low risk of significant hearing loss and may
      warrant conservative management while the presence of baseline hearing loss and
      large IAC volume resulted in higher ADHR and greater risk for further hearing
      loss and may benefit from early treatment interventions.

PMID- 29342059
TI  - Patients Living Alone Can Be Safely Discharged Directly Home After Total Joint
      Arthroplasty: A Prospective Cohort Study.
AB  - BACKGROUND: Despite the expense and potential hazards of inpatient
      rehabilitation, there is a prevailing belief that patients living alone cannot be
      safely discharged directly home after total joint arthroplasty. The purpose of
      this study was to assess the safety and efficacy of direct home discharge for
      patients living alone during convalescence after primary total joint
      arthroplasty. METHODS: We prospectively studied 910 consecutive patients
      undergoing primary, unilateral total hip arthroplasty or total knee arthroplasty
      over an 8-month period. Patients discharged directly home who were living alone
      for the first 2 weeks after the surgical procedure were identified as the
      investigational group and those discharged to home and living with others
      constituted the control group. The primary outcomes were 90-day complications and
      unplanned clinical events, including readmissions, emergency department or urgent
      care visits, and office visits. Functional outcomes, patient satisfaction, pain
      relief, and return to daily function were also assessed. RESULTS: During the
      study period, 874 patients (96%) were discharged directly home and only 36
      patients (4%) were discharged to a rehabilitation facility. Of those discharged
      home, 769 patients were included in the final analysis, including 138 patients
      living alone and 631 patients living with others, and 105 patients were excluded
      as they opted not to participate. Patients living alone more commonly stayed an
      additional night in the hospital and utilized more home health services. There
      was no increase in complications or unplanned clinical events for patients living
      alone compared with those living with others. Further, no significant differences
      in functional outcomes or pain relief were detected, and satisfaction scores were
      equivalent after 90 days. CONCLUSIONS: Patients living alone had a safe and
      manageable recovery when discharged directly home after total joint arthroplasty.
      Extending the initial hospitalization and providing home health services on a
      selected basis may be a more cost-effective approach than routine discharge to an
      inpatient rehabilitation facility. LEVEL OF EVIDENCE: Therapeutic Level II. See
      Instructions for Authors for a complete description of levels of evidence.

PMID- 29342060
TI  - Creep and Wear in Vitamin E-Infused Highly Cross-Linked Polyethylene Cups for
      Total Hip Arthroplasty: A Prospective Randomized Controlled Trial.
AB  - BACKGROUND: Aseptic loosening, the most common indication for revision surgery in
      total hip arthroplasty, can result from osteolysis caused by polyethylene (PE)
      wear particles. PE wear is increased by age-related oxidation of PE and free
      radicals emerging during irradiation cross-linking. Diffusion of vitamin E into
      PE stabilizes free radicals to maintain the biomechanical properties of PE. The
      purpose of this study was to determine whether vitamin E-infused highly cross
      linked PE cups could reduce wear rates. METHODS: We performed a prospective
      randomized controlled trial, in which 62 patients were allocated to 2 groups: a
      study group that received a vitamin E-infused highly cross-linked PE (HXLPE/VitE)
      cup and a control group that received an ultra-high molecular weight PE (UHMWPE)
      cup. Using radiostereometric analysis, we measured the penetration of the femoral
      head into the cup 7 days after surgery (baseline) and then again at 6 months and
      at 1, 2, and 3 years later. RESULTS: Baseline variables did not differ
      significantly between the groups. At 1, 2, and 3 years after surgery, the
      HXLPE/VitE cup showed significantly less cumulative penetration (creep and wear)
      than the UHMWPE cup (p = 0.004, p < 0.0001, and p < 0.0001, respectively). The
      cumulative penetration after 3 years was 0.200 mm for the HXLPE/VitE cup versus
      0.317 mm for the UHMWPE cup (p < 0.0001). From 1 to 3 years after surgery, after
      creep had stabilized and further penetration was mainly due to wear, the mean
      penetration increased only 0.04 mm in the HXLPE/VitE cup and 0.116 mm in the
      UHMWPE cup. CONCLUSIONS: Our results confirm that wear rates over the first 3
      years following surgery were lower in HXLPE/VitE cups than in UHMWPE cups. This
      suggests that HXLPE/VitE cups may prevent osteolysis, implant loosening, and
      eventually revision surgery. Long-term follow-up data continue to be collected to
      confirm these findings. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions
      for Authors for a complete description of levels of evidence.

PMID- 29342061
TI  - The Effect of Alternative Bearing Surfaces on the Risk of Revision Due to
      Infection in Minimally Stabilized Total Knee Replacement: An Analysis of 326,603
      Prostheses from the Australian Orthopaedic Association National Joint Replacement
      Registry.
AB  - BACKGROUND: The effect of alternative bearing materials on the risk of revision
      due to infection after total knee replacement remains uncertain. By reducing the
      immunomodulating polyethylene wear-particle burden and with different substrate
      bacterial adhesion properties, Oxinium oxidized zirconium and cross-linked
      polyethylene (XLPE) could alter infection risk. The purpose of the current study
      was to analyze the risk of revision for infection in 3 comparisons of bearing
      combinations. METHODS: To evaluate the risk of revision for infection with XLPE,
      cobalt-chromium (CoCr) on XLPE was compared with CoCr on non-cross-linked
      polyethylene (NXLPE). To evaluate Oxinium, Oxinium-NXLPE was compared with CoCr
      NXLPE, and to evaluate the possibility of an additional beneficial effect of
      Oxinium on XLPE, Oxinium-XLPE was compared with CoCr-XLPE. The cumulative percent
      revision (CPR) and hazard ratio (HR) for revision for infection in primary total
      knee replacement for osteoarthritis were determined from registry data from
      September 1, 1999, to December 31, 2015. Revisions within 6 months following the
      primary surgery were censored from the analysis, while procedures with posterior
      stabilized or fully stabilized total knee replacements as well as prostheses with
      a known higher risk of revision were excluded. Analyses were stratified by age,
      sex, and fixation type. RESULTS: Of the 326,603 included primary total knee
      replacements, 1,511 (0.46%) were revised for infection. The risk of revision for
      infection was lower for CoCr-XLPE compared with CoCr-NXLPE (HR = 0.74; 95%
      confidence interval [CI] = 0.65 to 0.84; p < 0.001). This effect was apparent for
      both male and female patients overall, all fixation types, antibiotic cement use,
      those <65 years of age, and male patients >=65 years of age. However, for female
      patients >=65 years of age, there was no difference. Overall, Oxinium-NXLPE had
      the same revision risk as CoCr-NXLPE regardless of fixation; however, for
      cemented fixation, subanalysis showed a lower risk for Oxinium-NXLPE compared
      with CoCr-NXLPE (HR = 0.69; 95% CI = 0.51 to 0.94; p = 0.018). Oxinium-XLPE had
      the same revision risk for infection as CoCr-XLPE overall, among male patients,
      and when cemented fixation had been used. CONCLUSIONS: In this registry analysis,
      CoCr-XLPE had a 26% lower risk of revision for infection than CoCr-NXLPE,
      suggesting a reduction of wear particle-induced immunomodulation with XLPE.
      Oxinium-XLPE had the same risk as CoCr-XLPE. Overall, Oxinium did not reduce the
      infection risk. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for
      Authors for a complete description of levels of evidence.

PMID- 29342062
TI  - Potential Sex Bias Exists in Orthopaedic Basic Science and Translational
      Research.
AB  - BACKGROUND: Potential sex bias has been shown in general surgery basic science
      and translational research, with unequal representation of male and female
      specimens. Because basic science research forms the foundation for clinical
      studies on which patient care is based, it is important that this research
      equally consider both sexes. The purpose of this study was to determine if
      potential sex bias exists in the basic science and translational orthopaedic
      literature. METHODS: A systematic review was conducted of all articles published
      in 2014 in The Journal of Bone & Joint Surgery, Clinical Orthopaedics and Related
      Research, The Bone & Joint Journal, and the Journal of Orthopaedic Research
      (JOR). All original research articles utilizing animals, cells, or cadavers were
      included. The data abstracted included study type, sex of specimen studied, and
      presence of sex-based reporting of data. A second review was performed of all
      basic science articles published in JOR in 1994, 2004, and 2014 to compare sex
      bias trends across 3 decades. Distributions of variables were compared using the
      Fisher exact test, with significance defined as p < 0.05. RESULTS: Of 1,693
      articles reviewed, 250 (15%) were included: 122 animal-based studies (49%), 71
      cell-based studies (28%), and 57 human cadaver-based studies (23%). Overall,
      authors in 88 studies (35%) did not report the sex of animals, cells, or cadavers
      used. Of 162 studies in which the authors did report sex, 69 (43%) utilized male
      only, 40 (25%) utilized female only, and 53 (33%) utilized both sexes. Of those
      studies that used both sexes, authors in only 7 studies (13%) reported sex-based
      results. A subanalysis of JOR articles across 3 decades revealed a significant
      increase in studies specifying sex (p = 0.01) from 2004 to 2014. CONCLUSIONS:
      Potential sex bias exists in orthopaedic surgery basic science and translational
      research, with an overrepresentation of male specimens. CLINICAL RELEVANCE:
      Inequality in sex representation must be addressed as basic science and
      translational research creates the foundation for subsequent clinical research,
      which ultimately informs clinical care.

PMID- 29342063
TI  - Low Prevalence of Hip and Knee Arthritis in Active Marathon Runners.
AB  - BACKGROUND: Existing evidence on whether marathon running contributes to hip and
      knee arthritis is inconclusive. Our aim was to describe hip and knee health in
      active marathon runners, including the prevalence of pain, arthritis, and
      arthroplasty, and associated risk factors. METHODS: A hip and knee health survey
      was distributed internationally to marathon runners. Active marathoners who
      completed >=5 marathons and were currently running a minimum of 10 miles per week
      were included (n = 675). Questions assessed pain, personal and family history of
      arthritis, surgical history, running volume, personal record time, and current
      running status. Multivariable analyses identified risk factors for pain and
      arthritis. Arthritis prevalence in U.S. marathoners was compared with National
      Center for Health Statistics prevalence estimates for a matched group of the U.S.
      POPULATION:  RESULTS: Marathoners (n = 675) with a mean age of 48 years (range,
      18 to 79 years) ran a mean distance of 36 miles weekly (range, 10 to 150 miles
      weekly) over a mean time of 19 years (range, 3 to 60 years) and completed a mean
      of 76 marathons (range, 5 to 1,016 marathons). Hip or knee pain was reported by
      47%, and arthritis was reported by 8.9% of marathoners. Arthritis prevalence was
      8.8% for the subgroup of U.S. marathoners, significantly lower (p < 0.001) than
      the prevalence in the matched U.S. population (17.9%) and in subgroups stratified
      by age, sex, body mass index (BMI), and physical activity level (p < 0.001).
      Seven marathoners continued to run following hip or knee arthroplasty. Age and
      family and surgical history were independent risk factors for arthritis. There
      was no significant risk associated with running duration, intensity, mileage, or
      the number of marathons completed (p > 0.05). CONCLUSIONS: Age, family history,
      and surgical history independently predicted an increased risk for hip and knee
      arthritis in active marathoners, although there was no correlation with running
      history. In our cohort, the arthritis rate of active marathoners was below that
      of the general U.S. POPULATION: Longitudinal follow-up is needed to determine the
      effects of marathon running on developing future hip and knee arthritis. LEVEL OF
      EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete
      description of levels of evidence.

PMID- 29342064
TI  - Minimally Manipulated Bone Marrow Concentrate Compared with Microfracture
      Treatment of Full-Thickness Chondral Defects: A One-Year Study in an Equine
      Model.
AB  - BACKGROUND: Microfracture is commonly performed for cartilage repair but usually
      results in fibrocartilage. Microfracture augmented by autologous bone marrow
      concentrate (BMC) was previously shown to yield structurally superior cartilage
      repairs in an equine model compared with microfracture alone. The current study
      was performed to test the hypothesis that autologous BMC without concomitant
      microfracture improves cartilage repair compared with microfracture alone.
      METHODS: Autologous sternal bone marrow aspirate (BMA) was concentrated using a
      commercial system. Cells from BMC were evaluated for chondrogenic potential in
      vitro and in vivo. Bilateral full-thickness chondral defects (15-mm diameter)
      were created on the midlateral trochlear ridge in 8 horses. Paired defects were
      randomly assigned to treatment with BMC without concomitant microfracture, or to
      microfracture alone. The repairs were evaluated at 1 year by in vitro assessment,
      arthroscopy, morphological magnetic resonance imaging (MRI), quantitative T2
      weighted and ultrashort echo time enhanced T2* (UTE-T2*) MRI mapping, and
      histological assessment. RESULTS: Culture-expanded but not freshly isolated cells
      from BMA and BMC underwent cartilage differentiation in vitro. In vivo, cartilage
      repairs in both groups were fibrous to fibrocartilaginous at 1 year of follow-up,
      with no differences observed between BMC and microfracture by arthroscopy, T2 and
      UTE-T2* MRI values, and histological assessment (p > 0.05). Morphological MRI
      showed subchondral bone changes not observed by arthroscopy and improved overall
      outcomes for the BMC repairs (p = 0.03). Differences in repair tissue UTE-T2*
      texture features were observed between the treatment groups (p < 0.05).
      CONCLUSIONS: When BMC was applied directly to critical-sized, full-thickness
      chondral defects in an equine model, the cartilage repair results were similar to
      those of microfracture. Our data suggest that, given the few mesenchymal stem
      cells in minimally manipulated BMC, other mechanisms such as paracrine, anti
      inflammatory, or immunomodulatory effects may have been responsible for tissue
      regeneration in a previous study in which BMC was applied to microfractured
      repairs. While our conclusions are limited by small numbers, the better MRI
      outcomes for the BMC repairs may have been related to reduced surgical trauma to
      the subchondral bone. CLINICAL RELEVANCE: MRI provides important information on
      chondral defect subsurface repair organization and subchondral bone structure
      that is not well assessed by arthroscopy.

PMID- 29342065
TI  - Diagnosis of Periprosthetic Joint Infection: The Potential of Next-Generation
      Sequencing.
AB  - BACKGROUND: Next-generation sequencing is a well-established technique for
      sequencing of DNA and has recently gained attention in many fields of medicine.
      Our aim was to evaluate the accuracy of next-generation sequencing in identifying
      the causative organism(s) in patients with periprosthetic joint infection.
      METHODS: In this prospective study, samples were collected from 65 revision
      arthroplasties (39 knees and 26 hips) and 17 primary arthroplasties (9 hips and 8
      knees). Synovial fluid, deep tissue, and swabs were obtained at the time of the
      surgical procedure and were shipped to the laboratory for next-generation
      sequencing. Deep-tissue specimens were also sent to the institutional laboratory
      for culture. Sensitivity and specificity were calculated for next-generation
      sequencing, using the Musculoskeletal Infection Society (MSIS) definition of
      periprosthetic joint infection as the standard. RESULTS: In 28 revisions, the
      cases were considered to be infected; cultures were positive in 17 cases (60.7%
      [95% confidence interval (CI), 40.6% to 78.5%]), and next-generation sequencing
      was positive in 25 cases (89.3% [95% CI, 71.8% to 97.7%]), with concordance
      between next-generation sequencing and culture in 15 cases. Among the 11 cases of
      culture-negative periprosthetic joint infection, next-generation sequencing was
      able to identify an organism in 9 cases (81.8% [95% CI, 48.2% to 97.7%]). Next
      generation sequencing identified microbes in 9 (25.0% [95% CI, 12.1% to 42.2%])
      of 36 aseptic revisions with negative cultures and in 6 (35.3% [95% CI, 14.2% to
      61.7%]) of 17 primary total joint arthroplasties. Next-generation sequencing
      detected several organisms in most positive samples. However, in the majority of
      patients who were infected, 1 or 2 organisms were dominant. CONCLUSIONS: Next
      generation sequencing may be a useful adjunct in identification of the causative
      organism(s) in culture-negative periprosthetic joint infection. Our findings
      suggest that some cases of monomicrobial periprosthetic joint infection may have
      additional organisms that escape detection when culture is used. Further study is
      required to determine the clinical implications of isolated organisms in samples
      from patients who are not thought to be infected. LEVEL OF EVIDENCE: Diagnostic
      Level I. See Instructions for Authors for a complete description of levels of
      evidence.

PMID- 29342066
TI  - Resident Participation in Fixation of Intertrochanteric Hip Fractures: Analysis
      of the NSQIP Database.
AB  - BACKGROUND: Future generations of orthopaedic surgeons must continue to be
      trained in the surgical management of hip fractures. This study assesses the
      effect of resident participation on outcomes for the treatment of
      intertrochanteric hip fractures. METHODS: The National Surgical Quality
      Improvement Program (NSQIP) database (2010 to 2013) was queried for
      intertrochanteric hip fractures (International Classification of Diseases, 9th
      Revision, Clinical Modification [ICD-9-CM] code 820.21) treated with either
      extramedullary (Current Procedural Terminology [CPT] code 27244) or
      intramedullary (CPT code 27245) fixation. Demographic variables, including
      resident participation, as well as primary (death and serious morbidity) and
      secondary outcome variables were extracted for analysis. Univariate, propensity
      score-matched, and multivariate logistic regression analyses were performed to
      evaluate outcome variables. RESULTS: Data on resident participation were
      available for 1,764 cases (21.0%). Univariate analyses for all intertrochanteric
      hip fractures demonstrated no significant difference in 30-day mortality (6.3%
      versus 7.8%; p = 0.264) or serious morbidity (44.9% versus 43.2%; p = 0.506)
      between the groups with and without resident participation. Multivariate and
      propensity score-matched analyses gave similar results. Resident involvement was
      associated with prolonged operating-room time, length of stay, and time to
      discharge when a prolonged case was defined as one above the 90th percentile for
      time parameters. CONCLUSIONS: Resident participation was not associated with an
      increase in morbidity or mortality but was associated with an increase in time
      related secondary outcome measures. While attending surgeon supervision is
      necessary, residents can and should be involved in the care of these patients
      without concern that resident involvement negatively impacts perioperative
      morbidity and mortality. LEVEL OF EVIDENCE: Therapeutic Level III. See
      Instructions for Authors for a complete description of levels of evidence.

PMID- 29342067
TI  - There Is No Column: A New Classification for Acetabular Fractures.
AB  - BACKGROUND: The surgical treatment of acetabular fractures relies on the
      understanding of fracture architecture and their classification. The Judet and
      Letournel classification has been the cornerstone in understanding and treating
      acetabular fractures. Recently, there has been growing evidence of discrepancies
      and incompleteness in the Judet and Letournel classification, adversely affecting
      its clinical use. This study describes a novel comprehensive classification
      system that will direct surgical approach and fixation methods. METHODS: A
      retrospective study of patients with acetabular fractures treated at a level-I
      trauma center also serving as a referral center for acetabular fractures was
      performed. Fractures were classified according to both the novel and Judet and
      Letournel classification systems. The novel classification developed integrates
      the displacement vector (posterior, superomedial, or combined) and the fractured
      anatomic structures (anteroposterior wall, pelvic brim, iliac wing, quadrilateral
      plate, and ischium). Furthermore, postoperative malreduction was evaluated on the
      basis of intra-articular gap measurements in either anteroposterior or Judet
      oblique views. RESULTS: The study included 229 patients with acetabular fractures
      treated between 2007 and 2016. The mean patient age (and standard deviation) was
      46.7 +/- 21.75 years, and 172 patients (75.1%) were surgically treated. According
      to the novel classification system, the posterior displacement vector group
      included 60 patients, the superomedial displacement vector group included 130
      patients, the combined displacement vector group included 36 patients, and 3
      patients were unclassified by the new system. Forty-six patients (20.1%) could
      not be classified by the Judet and Letournel classification. Pelvic-brim fracture
      patterns were described as along the pelvic brim, across the pelvic brim, or
      comminuted. The quadrilateral plate primary fracture line was shown to be
      perpendicular to the pelvic brim. The selection of surgical approach and fixation
      methods depends on the fracture type. CONCLUSIONS: This study presents a novel
      classification system for acetabular fractures. It offers a complete
      classification system, encompassing nearly all fracture patterns. As the
      selection of surgical approach and fixation methods depends on fracture
      classification and understanding, the novel classification system can aid the
      surgeon with decision-making.

PMID- 29342068
TI  - What's New in Adult Reconstructive Knee Surgery.

PMID- 29342069
TI  - Orthopaedics in Haiti.

PMID- 29342070
TI  - An Evaluation of Industry Relationships Among Contributors to AAOS Clinical
      Practice Guidelines and Appropriate Use Criteria.
AB  - BACKGROUND: A long-standing relationship between orthopaedic surgeons and
      industry has made financial conflicts of interest a concerning issue. Research
      supports that financial conflicts of interest can influence both medical research
      and clinical practice. Financial conflicts of interest may also influence
      clinical practice guideline recommendations and their corresponding appropriate
      use criteria. Because of the influential nature of these guidelines, it is
      imperative that care be taken to minimize bias during guideline development.
      METHODS: We retrieved clinical practice guidelines and their corresponding
      appropriate use criteria from the American Academy of Orthopaedic Surgery that
      were published or revised between 2013 and 2016. We extracted industry payments
      received by physicians using the Centers for Medicare & Medicaid Services Open
      Payments database. We then evaluated the value and types of these payments. We
      also used these data to determine whether disclosure statements were accurate and
      whether guideline development was in adherence with the Institute of Medicine's
      (IOM's) standards. RESULTS: Of the 106 physicians that were evaluated, 85 (80%)
      received at least 1 industry payment, 56 (53%) accepted >$1,000, and 35 (33%)
      accepted >$10,000. Financial payments amounted to a mean of $93,512 per
      physician. Total reimbursement for the 85 clinical practice guideline and
      appropriate use criteria contributors was $9,912,309. We found that disclosure
      statements disagreed with the Open Payments data and that the IOM standards were
      not completely enforced. CONCLUSIONS: Clinical practice guideline and appropriate
      use criteria contributors received substantial payments from industry, many
      disclosure statements were inaccurate, and the IOM standards were not completely
      met. CLINICAL RELEVANCE: Clinical practice guidelines and appropriate use
      criteria are critical for practicing evidence-based medicine. If financial
      conflicts of interest are present during their development, it is possible that
      patient care may be compromised.

PMID- 29342071
TI  - Why We Should Care About the Sex of Specimens in Cadaveric, Animal, and Cell
      Based Orthopaedic Research: Commentary on an article by Jessica Bryant, MD, et
      al.: "Potential Sex Bias Exists in Orthopaedic Basic Science and Translational
      Research".

PMID- 29342072
TI  - Decreased Osteoarthritis Risk in Experienced Marathon Runners: Commentary on an
      article by Danielle Y. Ponzio, MD, et al.: "Low Prevalence of Hip and Knee
      Arthritis in Active Marathon Runners".

PMID- 29342073
TI  - Structure Elucidation of Unknown Metabolites in Metabolomics by Combined NMR and
      MS/MS Prediction.
AB  - We introduce a cheminformatics approach that combines highly selective and
      orthogonal structure elucidation parameters; accurate mass, MS/MS (MS2), and NMR
      into a single analysis platform to accurately identify unknown metabolites in
      untargeted studies. The approach starts with an unknown LC-MS feature, and then
      combines the experimental MS/MS and NMR information of the unknown to effectively
      filter out the false positive candidate structures based on their predicted MS/MS
      and NMR spectra. We demonstrate the approach on a model mixture, and then we
      identify an uncatalogued secondary metabolite in Arabidopsis thaliana. The
      NMR/MS2 approach is well suited to the discovery of new metabolites in plant
      extracts, microbes, soils, dissolved organic matter, food extracts, biofuels, and
      biomedical samples, facilitating the identification of metabolites that are not
      present in experimental NMR and MS metabolomics databases.

PMID- 29342074
TI  - Characterization of an Additive Manufactured TiAl Alloy-Steel Joint Produced by
      Electron Beam Welding.
AB  - In this work, the characterization of the assembly of a steel shaft into a gamma
      TiAl part for turbocharger application, obtained using Electron Beam Welding
      (EBW) technology with a Ni-based filler, was carried out. The Ti-48Al-2Nb-0.7Cr
      0.3Si (at %) alloy part was produced by Electron Beam Melting (EBM). This
      additive manufacturing technology allows the production of a lightweight part
      with complex shapes. The replacement of Nickel-based superalloys with TiAl alloys
      in turbocharger automotive applications will lead to an improvement of the engine
      performance and a substantial reduction in fuel consumption and emission. The
      welding process allows a promising joint to be obtained, not affecting the TiAl
      microstructure. Nevertheless, it causes the formation of diffusive layers between
      the Ni-based filler and both steel and TiAl, with the latter side being
      characterized by a very complex microstructure, which was fully characterized in
      this paper by means of Scanning Electron Microscopy, Energy Dispersive X-ray
      Spectroscopy, and nanoindentation. The diffusive interface has a thickness of
      about 6 um, and it is composed of several layers. Specifically, from the TiAl
      alloy side, we find a layer of Ti3Al followed by Al3NiTi2 and AlNi2Ti.
      Subsequently Ni becomes more predominant, with a first layer characterized by
      abundant carbide/boride precipitation, and a second layer characterized by Si
      enrichment. Then, the chemical composition of the Ni-based filler is gradually
      reached.

PMID- 29342075
TI  - Enrichment and Identification of the Most Abundant Zinc Binding Proteins in
      Developing Barley Grains by Zinc-IMAC Capture and Nano LC-MS/MS.
AB  - Background: Zinc accumulates in the embryo, aleurone, and subaleurone layers at
      different amounts in cereal grains. Our hypothesis is that zinc could be stored
      bound, not only to low MW metabolites/proteins, but also to high MW proteins as
      well. Methods: In order to identify the most abundant zinc binding proteins in
      different grain tissues, we microdissected barley grains into (1) seed coats; (2)
      aleurone/subaleurone; (3) embryo; and (4) endosperm. Initial screening for
      putative zinc binding proteins from the different tissue types was performed by
      fractionating proteins according to solubility (Osborne fractionation), and
      resolving those via Sodium Dodecyl Sulfate Polyacrylamide Gel Electrophoresis
      (SDS-PAGE) followed by polyvinylidene fluoride (PVDF) membrane blotting and
      dithizone staining. Selected protein fractions were subjected to Zn2+-immobilized
      metal ion affinity chromatography, and the captured proteins were identified
      using nanoscale liquid chromatography coupled to tandem mass spectrometry (nanoLC
      MS/MS). Results: In the endosperm, the most abundant zinc binding proteins were
      the storage protein B-hordeins, gamma-, and D-hordeins, while in the embryo, 7S
      globulins storage proteins exhibited zinc binding. In the aleurone/subaleurone,
      zinc affinity captured proteins were late abundant embryogenesis proteins,
      dehydrins, many isoforms of non-specific lipid transfer proteins, and alpha
      amylase trypsin inhibitor. Conclusions: We have shown evidence that abundant
      barley grain proteins have been captured by Zn-IMAC, and their zinc binding
      properties in relationship to the possibility of zinc storage is discussed.

PMID- 29342076
TI  - Neuromorphic Vibrotactile Stimulation of Fingertips for Encoding Object Stiffness
      in Telepresence Sensory Substitution and Augmentation Applications.
AB  - We present a tactile telepresence system for real-time transmission of
      information about object stiffness to the human fingertips. Experimental tests
      were performed across two laboratories (Italy and Ireland). In the Italian
      laboratory, a mechatronic sensing platform indented different rubber samples.
      Information about rubber stiffness was converted into on-off events using a
      neuronal spiking model and sent to a vibrotactile glove in the Irish laboratory.
      Participants discriminated the variation of the stiffness of stimuli according to
      a two-alternative forced choice protocol. Stiffness discrimination was based on
      the variation of the temporal pattern of spikes generated during the indentation
      of the rubber samples. The results suggest that vibrotactile stimulation can
      effectively simulate surface stiffness when using neuronal spiking models to
      trigger vibrations in the haptic interface. Specifically, fractional variations
      of stiffness down to 0.67 were significantly discriminated with the developed
      neuromorphic haptic interface. This is a performance comparable, though slightly
      worse, to the threshold obtained in a benchmark experiment evaluating the same
      set of stimuli naturally with the own hand. Our paper presents a bioinspired
      method for delivering sensory feedback about object properties to human skin
      based on contingency-mimetic neuronal models, and can be useful for the design of
      high performance haptic devices.

PMID- 29342077
TI  - Use of a New International Classification of Health Interventions for Capturing
      Information on Health Interventions Relevant to People with Disabilities.
AB  - Development of the World Health Organization's International Classification of
      Health Interventions (ICHI) is currently underway. Once finalised, ICHI will
      provide a standard basis for collecting, aggregating, analysing, and comparing
      data on health interventions across all sectors of the health system. In this
      paper, we introduce the classification, describing its underlying tri-axial
      structure, organisation and content. We then discuss the potential value of ICHI
      for capturing information on met and unmet need for health interventions relevant
      to people with a disability, with a particular focus on interventions to support
      functioning and health promotion interventions. Early experiences of use of the
      Swedish National Classification of Social Care Interventions and Activities,
      which is based closely on ICHI, illustrate the value of a standard classification
      to support practice and collect statistical data. Testing of the ICHI beta
      version in a wide range of countries and contexts is now needed so that
      improvements can be made before it is finalised. Input from those with an
      interest in the health of people with disabilities and health promotion more
      broadly is welcomed.

PMID- 29342078
TI  - Spin Absorption Effect at Ferromagnet/Ge Schottky-Tunnel Contacts.
AB  - We study the influence of the junction size in ferromagnet (FM)/semiconductor
      (SC) contacts on four-terminal nonlocal spin signals in SC-based lateral spin
      valve (LSV) structures. When we use FM/Ge Schottky-tunnel junctions with
      relatively low resistance-area products, the magnitude of the nonlocal spin
      signal depends clearly on the junction size, indicating the presence of the spin
      absorption effect at the spin-injector contact. The temperature-dependent spin
      signal can also be affected by the spin absorption effect. For SC spintronic
      applications with a low parasitic resistance, we should consider the influence of
      the spin absorption on the spin-transport signals in SC-based device structures.

PMID- 29342079
TI  - Selective Laser Melting Produced Ti-6Al-4V: Post-Process Heat Treatments to
      Achieve Superior Tensile Properties.
AB  - Current post-process heat treatments applied to selective laser melting produced
      Ti-6Al-4V do not achieve the same microstructure and therefore superior tensile
      behaviour of thermomechanical processed wrought Ti-6Al-4V. Due to the growing
      demand for selective laser melting produced parts in industry, research and
      development towards improved mechanical properties is ongoing. This study is
      aimed at developing post-process annealing strategies to improve tensile
      behaviour of selective laser melting produced Ti-6Al-4V parts. Optical and
      electron microscopy was used to study alpha grain morphology as a function of
      annealing temperature, hold time and cooling rate. Quasi-static uniaxial tensile
      tests were used to measure tensile behaviour of different annealed parts. It was
      found that elongated alpha'/alpha grains can be fragmented into equiaxial grains
      through applying a high temperature annealing strategy. It is shown that bi-modal
      microstructures achieve a superior tensile ductility to current heat treated
      selective laser melting produced Ti-6Al-4V samples.

PMID- 29342080
TI  - Comparisons of Different Models on Dynamic Recrystallization of Plate during
      Asymmetrical Shear Rolling.
AB  - Asymmetrical shear rolling with velocity asymmetry and geometry asymmetry is
      beneficial to enlarge deformation and refine grain size at the center of the
      thick plate compared to conventional symmetrical rolling. Dynamic
      recrystallization (DRX) plays a vital role in grain refinement during hot
      deformation. Finite element models (FEM) coupled with microstructure evolution
      models and cellular automata models (CA) are established to study the
      microstructure evolution of plate during asymmetrical shear rolling. The results
      show that a larger DRX fraction and a smaller average grain size can be obtained
      at the lower layer of the plate. The DRX fraction at the lower part increases
      with the ascending speed ratio, while that at upper part decreases. With the
      increase of the offset distance, the DRX fraction slightly decreases for the
      whole thickness of the plate. The differences in the DRX fraction and average
      grain size between the upper and lower surfaces increase with the ascending speed
      ratio; however, it varies little with the change of the speed ratio. Experiments
      are conducted and the CA models have a higher accuracy than FEM models as the
      grain morphology, DRX nuclei, and grain growth are taken into consideration in CA
      models, which are more similar to the actual DRX process during hot deformation.

PMID- 29342081
TI  - Age and Gender Differences in Psychological Distress among African Americans and
      Whites: Findings from the 2016 National Health Interview Survey.
AB  - Previous studies report a race and mental health paradox: Whites score higher on
      measures of major depression compared to African Americans, but the opposite is
      true for psychological distress (i.e., African Americans score higher on distress
      measures compared to Whites). Independently, race, age, and gender outcomes for
      psychological distress are well documented in the literature. However, there is
      relatively little research on how psychological distress interferes with the
      lives of African Americans and Whites at the intersection of their various race,
      age, and gender identities. This study uses data from the 2016 National Health
      Interview Survey to examine age and gender differences in psychological distress
      and how much psychological distress interferes with the lives of African
      Americans and Whites. Our study findings are contrary to the paradox such that
      young White women (M = 3.36, SD = 1.14) and middle-aged White men (M = 2.55, SD =
      3.97) experienced higher psychological distress than all other race, age, and
      gender groups. Psychological distress interference was relatively high among the
      high distress groups, except for older African American men (M = 1.73, SD = 1.05)
      and young African American women (M = 1.93, SD = 0.95). Implications for studies
      that consider cultural experiences of psychological distress, and how it impacts
      different demographic groups are discussed.

PMID- 29342082
TI  - Lewis Pair Catalysts in the Polymerization of Lactide and Related Cyclic Esters.
AB  - Polyesters, especially poly(lactide) (PLA), are used widely as biodegradable and
      biocompatible materials, yet their controllable synthesis, especially the
      stereoselective synthesis of polyesters, is still a challenge. Recently some
      excellent Lewis pair catalysts for ring-opening polymerization (ROP) of lactide
      and related cyclic esters have emerged. This review article will highlight the
      key advances in the ROP catalyzed by Lewis pair compounds with the aim of
      encouraging the wider application of Lewis pair catalysts in the polymerization
      of lactide and related cyclic esters.

PMID- 29342083
TI  - Regulation of Mitochondrial Dynamics by Proteolytic Processing and Protein
      Turnover.
AB  - The mitochondrial network is a dynamic organization within eukaryotic cells that
      participates in a variety of essential cellular processes, such as adenosine
      triphosphate (ATP) synthesis, central metabolism, apoptosis and inflammation. The
      mitochondrial network is balanced between rates of fusion and fission that
      respond to pathophysiologic signals to coordinate appropriate mitochondrial
      processes. Mitochondrial fusion and fission are regulated by proteins that either
      reside in or translocate to the inner or outer mitochondrial membranes or are
      soluble in the inter-membrane space. Mitochondrial fission and fusion are
      performed by guanosine triphosphatases (GTPases) on the outer and inner
      mitochondrial membranes with the assistance of other mitochondrial proteins. Due
      to the essential nature of mitochondrial function for cellular homeostasis,
      regulation of mitochondrial dynamics is under strict control. Some of the
      mechanisms used to regulate the function of these proteins are post-translational
      proteolysis and/or turnover, and this review will discuss these mechanisms
      required for correct mitochondrial network organization.

PMID- 29342085
TI  - Development of a Region-Specific Physiologically Based Pharmacokinetic Brain
      Model to Assess Hippocampus and Frontal Cortex Pharmacokinetics.
AB  - Central nervous system drug discovery and development is hindered by the
      impermeable nature of the blood-brain barrier. Pharmacokinetic modeling can
      provide a novel approach to estimate CNS drug exposure; however, existing models
      do not predict temporal drug concentrations in distinct brain regions. A rat CNS
      physiologically based pharmacokinetic (PBPK) model was developed, incorporating
      brain compartments for the frontal cortex (FC), hippocampus (HC), "rest-of-brain"
      (ROB), and cerebrospinal fluid (CSF). Model predictions of FC and HC Cmax, tmax
      and AUC were within 2-fold of that reported for carbamazepine and phenytoin. The
      inclusion of a 30% coefficient of variation on regional brain tissue volumes, to
      assess the uncertainty of regional brain compartments volumes on predicted
      concentrations, resulted in a minimal level of sensitivity of model predictions.
      This model was subsequently extended to predict human brain morphine
      concentrations, and predicted a ROB Cmax of 21.7 +/- 6.41 ng/mL when compared to
      "better" (10.1 ng/mL) or "worse" (29.8 ng/mL) brain tissue regions with a FC Cmax
      of 62.12 +/- 17.32 ng/mL and a HC Cmax of 182.2 +/- 51.2 ng/mL. These results
      indicate that this simplified regional brain PBPK model is useful for forward
      prediction approaches in humans for estimating regional brain drug
      concentrations.

PMID- 29342086
TI  - Copy Number Variation in SOX6 Contributes to Chicken Muscle Development.
AB  - Copy number variations (CNVs), which cover many functional genes, are associated
      with complex diseases, phenotypic diversity and traits that are economically
      important to raising chickens. The sex-determining region Y-box 6 (Sox6) plays a
      key role in fast-twitch muscle fiber differentiation of zebrafish and mice, but
      it is still unknown whether SOX6 plays a role in chicken skeletal muscle
      development. We identified two copy number polymorphisms (CNPs) which were
      significantly related to different traits on the genome level in chickens by
      AccuCopy(r) and CNVplex(r) analyses. Notably, five white recessive rock (CN = 1,
      CN = 3) variant individuals and two Xinghua (CN = 3) variant individuals contain
      a CNP13 (chromosome5: 10,500,294-10,675,531) which overlaps with SOX6. There is a
      disordered region in SOX6 proteins 265-579 aa coded by a partial CNV overlapping
      region. A quantitative real-time polymerase chain reaction showed that the
      expression level of SOX6 mRNA was positively associated with CNV and highly
      expressed during the skeletal muscle cell differentiation in chickens. After the
      knockdown of the SOX6, the expression levels of IGFIR1, MYF6, SOX9, SHOX and
      CCND1 were significantly down-regulated. All of them directly linked to muscle
      development. These results suggest that the number of CNVs in the CNP13 is
      positively associated with the expression level of SOX6, which promotes the
      proliferation and differentiation of skeletal muscle cells by up-regulating the
      expression levels of the muscle-growth-related genes in chickens as in other
      animal species.

PMID- 29342088
TI  - Synthesis and Characterization of WO3/Graphene Nanocomposites for Enhanced
      Photocatalytic Activities by One-Step In-Situ Hydrothermal Reaction.
AB  - Tungsten trioxide (WO3) nanorods are synthesized on the surface of graphene (GR)
      sheets by using a one-step in-situ hydrothermal method employing sodium tungstate
      (Na2WO4.2H2O) and graphene oxide (GO) as precursors. The resulting WO3/GR
      nanocomposites are characterized by X-ray diffraction, Raman spectroscopy,
      transmission electron microscopy, scanning electron microscopy and X-ray
      photoelectron spectroscopy. The results confirm that the interface between WO3
      nanorod and graphene contains chemical bonds. The enhanced optical absorption
      properties are measured by UV-vis diffuse reflectance spectra. The photocatalytic
      activity of the WO3/GR nanocomposites under visible light is evaluated by the
      photodegradation of methylene blue, where the degradation rate of WO3/GR
      nanocomposites is shown to be double that of pure WO3. This is attributed to the
      synergistic effect of graphene and the WO3 nanorod, which greatly enhances the
      photocatalytic performance of the prepared sample, reduces the recombination of
      the photogenerated electron-hole pairs and increases the visible light absorption
      efficiency. Finally, the photocatalytic mechanism of the WO3/GR nanocomposites is
      presented. The synthesis of the prepared sample is convenient, direct and
      environmentally friendly. The study reports a highly efficient composite
      photocatalyst for the degradation of contaminants that can be applied to cleaning
      up the environment.

PMID- 29342087
TI  - Sophisticated Fowl: The Complex Behaviour and Cognitive Skills of Chickens and
      Red Junglefowl.
AB  - The world's most numerous bird, the domestic chicken, and their wild ancestor,
      the red junglefowl, have long been used as model species for animal behaviour
      research. Recently, this research has advanced our understanding of the social
      behaviour, personality, and cognition of fowl, and demonstrated their
      sophisticated behaviour and cognitive skills. Here, we overview some of this
      research, starting with describing research investigating the well-developed
      senses of fowl, before presenting how socially and cognitively complex they can
      be. The realisation that domestic chickens, our most abundant production animal,
      are behaviourally and cognitively sophisticated should encourage an increase in
      general appraise and fascination towards them. In turn, this should inspire
      increased use of them as both research and hobby animals, as well as improvements
      in their unfortunately often poor welfare.

PMID- 29342089
TI  - Chitosan Gel to Treat Pressure Ulcers: A Clinical Pilot Study.
AB  - Chitosan is biopolymer with promising properties in wound healing. Chronic wounds
      represent a significant burden to both the patient and the medical system. Among
      chronic wounds, pressure ulcers are one of the most common types of complex
      wound. The efficacy and the tolerability of chitosan gel formulation, prepared
      into the hospital pharmacy, in the treatment of pressure ulcers of moderate
      severity were evaluated. The endpoint of this phase II study was the reduction of
      the area of the lesion by at least 20% after four weeks of treatment. Thus, 20
      adult volunteers with pressure ulcers within predetermined parameters were
      involved in a 30 days study. Dressing change was performed twice a week at
      outpatient clinic upon chronic wounds management. In the 90% of patients involved
      in the study, the treatment was effective, with a reduction of the area of the
      lesion and wound healing progress. The study demonstrated the efficacy of the gel
      formulation for treatment of pressure ulcers, also providing a strong reduction
      of patient management costs.

PMID- 29342090
TI  - Development of Databases on Iodine in Foods and Dietary Supplements.
AB  - Iodine is an essential micronutrient required for normal growth and
      neurodevelopment; thus, an adequate intake of iodine is particularly important
      for pregnant and lactating women, and throughout childhood. Low levels of iodine
      in the soil and groundwater are common in many parts of the world, often leading
      to diets that are low in iodine. Widespread salt iodization has eradicated severe
      iodine deficiency, but mild-to-moderate deficiency is still prevalent even in
      many developed countries. To understand patterns of iodine intake and to develop
      strategies for improving intake, it is important to characterize all sources of
      dietary iodine, and national databases on the iodine content of major dietary
      contributors (including foods, beverages, water, salts, and supplements) provide
      a key information resource. This paper discusses the importance of well
      constructed databases on the iodine content of foods, beverages, and dietary
      supplements; the availability of iodine databases worldwide; and factors related
      to variability in iodine content that should be considered when developing such
      databases. We also describe current efforts in iodine database development in the
      United States, the use of iodine composition data to develop food fortification
      policies in New Zealand, and how iodine content databases might be used when
      considering the iodine intake and status of individuals and populations.

PMID- 29342091
TI  - DNA-Based Single-Molecule Electronics: From Concept to Function.
AB  - Beyond being the repository of genetic information, DNA is playing an
      increasingly important role as a building block for molecular electronics. Its
      inherent structural and molecular recognition properties render it a leading
      candidate for molecular electronics applications. The structural stability,
      diversity and programmability of DNA provide overwhelming freedom for the design
      and fabrication of molecular-scale devices. In the past two decades DNA has
      therefore attracted inordinate amounts of attention in molecular electronics.
      This review gives a brief survey of recent experimental progress in DNA-based
      single-molecule electronics with special focus on single-molecule conductance and
      I-V characteristics of individual DNA molecules. Existing challenges and exciting
      future opportunities are also discussed.

PMID- 29342093
TI  - Hydroxyl Ion Diffusion through Radicular Dentine When Calcium Hydroxide Is Used
      under Different Conditions.
AB  - Calcium hydroxide's anti-bacterial action relies on high pH. The aim here was to
      investigate hydroxyl ion diffusion through dentine under different conditions.
      Teeth were divided into control (n = 4) and four experimental groups (n = 10):
      Group 1-no medicament; Group 2-Calmix; Group 3-Calmix/Ledermix; Group 4-Calasept
      Plus/Ledermix; Group 5-Pulpdent/smear layer. Deep (inner dentine) and shallow
      (outer dentine) cavities were cut into each root. pH was measured in these
      cavities for 12 weeks. The inner and outer dentine pH in Group 2 was
      significantly higher than all groups. Inner dentine pH in Group 3 was slightly
      higher than that in Group 4 initially but subsequently comparable. After Day 2,
      Group 5 had significantly lower pH than Groups 3 and 4. The outer dentine pH in
      Group 3 started higher than that in Groups 4 and 5, but by Day 28 the difference
      was insignificant. The time for the inner dentine to reach maximum pH was one
      week for Group 2 and four weeks for Groups 3 and 4. The time for the outer
      dentine to reach maximum pH was eight weeks for all experimental groups. Mixing
      different Ca(OH)2 formulations with Ledermix gave similar hydroxyl ion release
      but pH and total diffusion was lower than Ca(OH)2 alone. The smear layer
      inhibited diffusion.

PMID- 29342092
TI  - Metabolic Alterations in Cancer Cells and the Emerging Role of Oncometabolites as
      Drivers of Neoplastic Change.
AB  - The mitochondrion is an important organelle and provides energy for a plethora of
      intracellular reactions. Metabolic dysregulation has dire consequences for the
      cell, and alteration in metabolism has been identified in multiple disease states
      cancer being one. Otto Warburg demonstrated that cancer cells, in the presence of
      oxygen, undergo glycolysis by reprogramming their metabolism-termed "aerobic
      glycolysis". Alterations in metabolism enable cancer cells to gain a growth
      advantage by obtaining precursors for macromolecule biosynthesis, such as nucleic
      acids and lipids. To date, several molecules, termed "oncometabolites", have been
      identified to be elevated in cancer cells and arise from mutations in nuclear
      encoded mitochondrial enzymes. Furthermore, there is evidence that
      oncometabolites can affect mitochondrial dynamics. It is believed that
      oncometabolites can assist in reprogramming enzymatic pathways and providing
      cancer cells with selective advantages. In this review, we will touch upon the
      effects of normal and aberrant mitochondrial metabolism in normal and cancer
      cells, the advantages of metabolic reprogramming, effects of oncometabolites on
      metabolism and mitochondrial dynamics and therapies aimed at targeting
      oncometabolites and metabolic aberrations.

PMID- 29342094
TI  - Telomeric Repeat-Containing RNAs (TERRA) Decrease in Squamous Cell Carcinoma of
      the Head and Neck Is Associated with Worsened Clinical Outcome.
AB  - Telomeres are transcribed into noncoding telomeric repeat-containing RNAs
      (TERRA), which are essential for telomere maintenance. Deregulation of TERRA
      transcription impairs telomere metabolism and a role in tumorigenesis has been
      proposed. Head and neck cancer (HNC) is one of the most frequent cancers
      worldwide, with head and neck squamous cell carcinoma (HNSCC) being the
      predominant type. Since HNSCC patients are characterized by altered telomere
      maintenance, a dysfunction in telomere transcription can be hypothesized. In this
      prospective study, we compared TERRA levels in the tumor and matched normal
      tissue from 23 HNSCC patients. We then classified patients in two categories
      according to the level of TERRA expression in the tumor compared to the normal
      tissue: (1) lower expression in the tumor, (2) higher or similar expression in
      tumor. A significant proportion of patients in the first group died of the
      disease within less than 34 months postsurgery, while the majority of patients in
      the second group were alive and disease-free. Our results highlight a striking
      correlation between TERRA expression and tumor aggressiveness in HNSCC suggesting
      that TERRA levels may be proposed as a novel molecular prognostic marker for
      HNSCC.

PMID- 29342095
TI  - Preparation of Cyano-Substituted Tetraphenylethylene Derivatives and Their
      Applications in Solution-Processable OLEDs.
AB  - Creation of organic luminescent materials with high solid-state efficiency is of
      vital importance for their applications in optoelectronic fields. Here, a series
      of AIE luminogens (AIE gens), (Z)-2,3-bis(4-(9,9-bis(6-(9H-carbazol-9-yl)hexyl)
      9H-fluoren-2-yl)phenyl)-3-phenylacrylonitrile (SFC), and 2,3-bis(4-(9,9-bis(6-(9H
      carbazol-9-yl)hexyl)-9H-fluoren-2-yl)phenyl)fumaronitrile (DFC), utilizing 2,3,3
      triphenylacrylonitrile and 2,3-diphenylfumaronitrile as respective centers, are
      designed and synthesized by Suzuki coupling reactions with high yields. The cis-
      and trans-isomers of DFC are also successfully obtained. All of them are
      thermally stable and show good solubility in common organic solvents. They all
      emit weakly in solution, but become strong emitters when fabricated into solid
      films. It is found introduction of one additional cyano group in DFC induced a
      big red-shift in solid-state emission, owing to its high electron-withdrawing
      ability. The cis- and trans-DFC show similar photophysical and Cyclic
      voltammogram (CV) behaviors. Non-doped solution-processed organic light-emitting
      diodes (OLEDs) using the three compounds as light-emitting layers are fabricated.
      SFC gives the best device performance with a maximum luminance of 5201 cd m-2, a
      maximum current efficiency of 3.67 cd A-1 and a maximum external quantum
      efficiencies (EQE) of 1.37%. Red-shifted EL spectra are observed for cis- and
      trans-DFC-based device, and the OLED using trans-DFC as active layer exhibits
      better performance, which might derive from their different conformation in film
      state.

PMID- 29342096
TI  - High-Resolution Lipidomics of the Early Life Stages of the Red Seaweed Porphyra
      dioica.
AB  - Porphyra dioica is a commercial seaweed consumed all over the world, mostly in
      the shape of nori sheets used for "sushi" preparation. It is a well-known part of
      the Asian diet with health benefits, which have been associated, among others, to
      the high levels of n-3 and n-6 fatty acids in this red alga. However, other
      highly valued lipids of Porphyra are polar lipids that remain largely undescribed
      and can have both nutritional value and bioactivity, thus could contribute to the
      valorization of this seaweed. In this context, the present work aims to identify
      the lipidome of two life cycle stages of the Atlantic species Porphyra dioica:
      the early life stage conchocelis produced in an indoor-nursery, and young blades
      produced outdoors using an integrated multitrophic aquaculture (IMTA) framework.
      Both the blades (gametophyte) and conchocelis (sporophyte) are commercialized in
      the food and cosmetics sectors. Liquid chromatography coupled to Q-Exactive high
      resolution-mass spectrometry (MS) platform was used to gain insight into the
      lipidome of these species. Our results allowed the identification of 110 and 100
      lipid molecular species in the lipidome of the blade and conchocelis,
      respectively. These lipid molecular species were distributed as follows
      (blade/conchocelis): 14/15 glycolipids (GLs), 93/79 phospholipids (PLs), and 3/6
      betaine lipids. Both life stages displayed a similar profile of GLs and comprised
      20:4(n-6) and 20:5(n-3) fatty acids that contribute to n-3 and n-6 fatty acid
      pool recorded and rank among the molecular species with higher potential
      bioactivity. PLs' profile was different between the two life stages surveyed,
      mainly due to the number and relative abundance of molecular species. This
      finding suggests that differences between both life stages were more likely
      related with shifts in the lipids of extraplastidial membranes rather than in
      plastidial membranes. PLs contained n-6 and n-3 precursors and in both life
      stages of Porphyra dioica the n-6/n-3 ratio recorded was less than 2,
      highlighting the potential benefits of using these life stages in human diet to
      prevent chronic diseases. Atherogenic and thrombogenic indexes of blades (0.85
      and 0.49, respectively) and conchocelis (0.34 and 0.30, respectively) are much
      lower than those reported for other Rhodophyta, which highlights their potential
      application as food or as functional ingredients. Overall, MS-based platforms
      represent a powerful tool to characterize lipid metabolism and target lipids
      along different life stages of algal species displaying complex life cycles (such
      as Porphyra dioica), contributing to their biotechnological application.

PMID- 29342097
TI  - Time Domain Near Infrared Spectroscopy Device for Monitoring Muscle Oxidative
      Metabolism: Custom Probe and In Vivo Applications.
AB  - Measurement of muscle oxidative metabolism is of interest for monitoring the
      training status in athletes and the rehabilitation process in patients. Time
      domain near infrared spectroscopy (TD NIRS) is an optical technique that allows
      the non-invasive measurement of the hemodynamic parameters in muscular tissue:
      concentrations of oxy- and deoxy-hemoglobin, total hemoglobin content, and tissue
      oxygen saturation. In this paper, we present a novel TD NIRS medical device for
      muscle oxidative metabolism. A custom-printed 3D probe, able to host optical
      elements for signal acquisition from muscle, was develop for TD NIRS in vivo
      measurements. The system was widely characterized on solid phantoms and during in
      vivo protocols on healthy subjects. In particular, we tested the in vivo
      repeatability of the measurements to quantify the error that we can have by
      repositioning the probe. Furthermore, we considered a series of acquisitions on
      different muscles that were not yet previously performed with this custom probe:
      a venous-arterial cuff occlusion of the arm muscle, a cycling exercise, and an
      isometric contraction of the vastus lateralis.

PMID- 29342098
TI  - Mechano-Enzymatic Deconstruction with a New Enzymatic Cocktail to Enhance
      Enzymatic Hydrolysis and Bioethanol Fermentation of Two Macroalgae Species.
AB  - The aim of this study was to explore the efficiency of a mechano-enzymatic
      deconstruction of two macroalgae species for sugars and bioethanol production, by
      using a new enzymatic cocktail (Haliatase) and two types of milling modes (vibro
      ball: VBM and centrifugal milling: CM). By increasing the enzymatic concentration
      from 3.4 to 30 g/L, the total sugars released after 72 h of hydrolysis increased
      (from 6.7 to 13.1 g/100 g TS and from 7.95 to 10.8 g/100 g TS for the green algae
      U. lactuca and the red algae G. sesquipedale, respectively). Conversely, total
      sugars released from G. sesquipedale increased (up to 126% and 129% after VBM and
      CM, respectively). The best bioethanol yield (6 geth/100 g TS) was reached after
      72 h of fermentation of U. lactuca and no increase was obtained after centrifugal
      milling. The latter led to an enhancement of the ethanol yield of G. sesquipedale
      (from 2 to 4 g/100 g TS).

PMID- 29342099
TI  - Poly(lactic acid) (PLA) Based Tear Resistant and Biodegradable Flexible Films by
      Blown Film Extrusion.
AB  - Poly(lactic acid) (PLA) was melt mixed in a laboratory extruder with
      poly(butylene adipate-co-terephthalate) (PBAT) and poly(butylene succinate) (PBS)
      in the presence of polypropylene glycol di glycidyl ether (EJ400) that acted as
      both plasticizer and compatibilizer. The process was then scaled up in a semi
      industrial extruder preparing pellets having different content of a nucleating
      agent (LAK). All of the formulations could be processed by blowing extrusion and
      the obtained films showed mechanical properties dependent on the LAK content. In
      particular the tearing strength showed a maximum like trend in the investigated
      composition range. The films prepared with both kinds of blends showed a tensile
      strength in the range 12-24 MPa, an elongation at break in the range 150-260% and
      a significant crystallinity.

PMID- 29342101
TI  - A Novel Methodology for Improving Plant Pest Surveillance in Vineyards and Crops
      Using UAV-Based Hyperspectral and Spatial Data.
AB  - Recent advances in remote sensed imagery and geospatial image processing using
      unmanned aerial vehicles (UAVs) have enabled the rapid and ongoing development of
      monitoring tools for crop management and the detection/surveillance of insect
      pests. This paper describes a (UAV) remote sensing-based methodology to increase
      the efficiency of existing surveillance practices (human inspectors and insect
      traps) for detecting pest infestations (e.g., grape phylloxera in vineyards). The
      methodology uses a UAV integrated with advanced digital hyperspectral,
      multispectral, and RGB sensors. We implemented the methodology for the
      development of a predictive model for phylloxera detection. In this method, we
      explore the combination of airborne RGB, multispectral, and hyperspectral imagery
      with ground-based data at two separate time periods and under different levels of
      phylloxera infestation. We describe the technology used-the sensors, the UAV, and
      the flight operations-the processing workflow of the datasets from each imagery
      type, and the methods for combining multiple airborne with ground-based datasets.
      Finally, we present relevant results of correlation between the different
      processed datasets. The objective of this research is to develop a novel
      methodology for collecting, processing, analising and integrating multispectral,
      hyperspectral, ground and spatial data to remote sense different variables in
      different applications, such as, in this case, plant pest surveillance. The
      development of such methodology would provide researchers, agronomists, and UAV
      practitioners reliable data collection protocols and methods to achieve faster
      processing techniques and integrate multiple sources of data in diverse remote
      sensing applications.

PMID- 29342100
TI  - Modulation of the Fungal-Host Interaction by the Intra-Species Diversity of C.
      albicans.
AB  - The incidence of human infections caused by the opportunistic fungal pathogen
      Candida albicans is on the rise due to increasing numbers of immunosuppressed
      patients. The importance of the immune system in preventing overgrowth of the
      colonizing fungus and thereby limiting infection is well recognized and host
      protective mechanisms widely investigated. Only recently, it was recognized that
      the natural diversity in the fungal species could also influence the outcome of
      the interaction between the fungus and the host. C. albicans strain-specific
      differences are complex and their regulation at the genomic, genetic, and
      epigenetic level and by environmental factors is only partially understood. In
      this review, we provide an overview of the natural diversity of C. albicans and
      discuss how it impacts host-fungal interactions and thereby affects the balance
      between commensalism versus disease.

PMID- 29342102
TI  - Development of a High-Sensitivity Wireless Accelerometer for Structural Health
      Monitoring.
AB  - Structural health monitoring (SHM) is playing an increasingly important role in
      ensuring the safety of structures. A shift of SHM research away from traditional
      wired methods toward the use of wireless smart sensors (WSS) has been motivated
      by the attractive features of wireless smart sensor networks (WSSN). The progress
      achieved in Micro Electro-Mechanical System (MEMS) technologies and wireless data
      transmission, has extended the effectiveness and range of applicability of WSSNs.
      One of the most common sensors employed in SHM strategies is the accelerometer;
      however, most accelerometers in WSS nodes have inadequate resolution for
      measurement of the typical accelerations found in many SHM applications. In this
      study, a high-resolution and low-noise tri-axial digital MEMS accelerometer is
      incorporated in a next-generation WSS platform, the Xnode. In addition to meeting
      the acceleration sensing demands of large-scale civil infrastructure
      applications, this new WSS node provides powerful hardware and a robust software
      framework to enable edge computing that can deliver actionable information.
      Hardware and software integration challenges are presented, and the associate
      resolutions are discussed. The performance of the wireless accelerometer is
      demonstrated experimentally through comparison with high-sensitivity wired
      accelerometers. This new high-sensitivity wireless accelerometer will extend the
      use of WSSN to a broader class of SHM applications.

PMID- 29342103
TI  - Minimally-Invasive Neural Interface for Distributed Wireless Electrocorticogram
      Recording Systems.
AB  - This paper presents a minimally-invasive neural interface for distributed
      wireless electrocorticogram (ECoG) recording systems. The proposed interface
      equips all necessary components for ECoG recording, such as the high performance
      front-end integrated circuits, a fabricated flexible microelectrode array, and
      wireless communication inside a miniaturized custom-made platform. The multiple
      units of the interface systems can be deployed to cover a broad range of the
      target brain region and transmit signals via a built-in intra-skin communication
      (ISCOM) module. The core integrated circuit (IC) consists of 16-channel, low
      power push-pull double-gated preamplifiers, in-channel successive approximation
      register analog-to-digital converters (SAR ADC) with a single-clocked
      bootstrapping switch and a time-delayed control unit, an ISCOM module for
      wireless data transfer through the skin instead of a power-hungry RF wireless
      transmitter, and a monolithic voltage/current reference generator to support the
      aforementioned analog and mixed-signal circuit blocks. The IC was fabricated
      using 250 nm CMOS processes in an area of 3.2 * 0.9 mm2 and achieved the low
      power operation of 2.5 uW per channel. Input-referred noise was measured as 5.62
      uVrms for 10 Hz to 10 kHz and ENOB of 7.21 at 31.25 kS/s. The implemented system
      successfully recorded multi-channel neural activities in vivo from a primate and
      demonstrated modular expandability using the ISCOM with power consumption of 160
      uW.

PMID- 29342104
TI  - Synthesis, Anti-Proliferative Activity Evaluation and 3D-QSAR Study of
      Naphthoquinone Derivatives as Potential Anti-Colorectal Cancer Agents.
AB  - Colorectal cancer (CRC) is a disease with high incidence and mortality,
      constituting the fourth most common cause of death from cancer worldwide.
      Naphthoquinones are attractive compounds due to their biological and structural
      properties. In this work, 36 naphthoquinone derivatives were synthesized and
      their activity evaluated against HT-29 cells. Overall, high to moderate anti
      proliferative activity was observed in most members of the series, with 15
      compounds classified as active (1.73 < IC50 < 18.11 MUM). The naphtho[2,3
      b]thiophene-4,9-dione analogs showed potent cytotoxicity, 8-hydroxy-2-(thiophen-2
      ylcarbonyl)naphtho[2,3-b]thiophene-4,9-dione being the compound with the highest
      potency and selectivity. Our results suggest that the toxicity is improved in
      molecules with tricyclic naphtho[2,3-b]furan-4,9-dione and naphtho[2,3
      b]thiophene-4,9-dione systems 2-substituted with an electron-withdrawing group. A
      3D-QSAR study of comparative molecular field analysis (CoMFA) was carried out,
      resulting in the generation of a reliable model (r2 = 0.99 and q2 = 0.625). This
      model allowed proposing five new compounds with two-fold higher theoretical anti
      proliferative activity, which would be worthwhile to synthesize and evaluate.
      Further investigations will be needed to determine the mechanism involved in the
      effect of most active compounds which are potential candidates for new anticancer
      agents.

PMID- 29342105
TI  - Neuroimmune-Driven Neuropathic Pain Establishment: A Focus on Gender Differences.
AB  - The role of neuroinflammatory cells in the establishment of neuropathic pain has
      been investigated in depth in the last few years. In particular, microglia have
      been shown to be key players in the induction of tactile allodynia, as they
      release proinflammatory molecules that, in turn, sensitize nociceptive neurons
      within the spinal cord. However, the role of peripheral immune cells such as
      macrophages, infiltrating monocytes, mast cells, and T-cells has been highlighted
      in the last few studies, even though the data are still conflicting and need to
      be clarified. Intriguingly, the central (microglia) and peripheral (T-cell)
      adaptive immune cells that orchestrate maladaptive process-driven neuropathic
      pain seem to be involved in a gender-dependent manner. In this review, we
      highlight the role of the microglia and peripheral immune cells in chronic
      degenerative disease associated with neuro-immune-inflammatory processes.

PMID- 29342106
TI  - Adrenergic Agonists Bind to Adrenergic-Receptor-Like Regions of the Mu Opioid
      Receptor, Enhancing Morphine and Methionine-Enkephalin Binding: A New Approach to
      "Biased Opioids"?
AB  - Extensive evidence demonstrates functional interactions between the adrenergic
      and opioid systems in a diversity of tissues and organs. While some effects are
      due to receptor and second messenger cross-talk, recent research has revealed an
      extracellular, allosteric opioid binding site on adrenergic receptors that
      enhances adrenergic activity and its duration. The present research addresses
      whether opioid receptors may have an equivalent extracellular, allosteric
      adrenergic binding site that has similar enhancing effects on opioid binding.
      Comparison of adrenergic and opioid receptor sequences revealed that these
      receptors share very significant regions of similarity, particularly in some of
      the extracellular and transmembrane regions associated with adrenergic binding in
      the adrenergic receptors. Five of these shared regions from the mu opioid
      receptor (muOPR) were synthesized as peptides and tested for binding to
      adrenergic, opioid and control compounds using ultraviolet spectroscopy.
      Adrenergic compounds bound to several of these muOPR peptides with low micromolar
      affinity while acetylcholine, histamine and various adrenergic antagonists did
      not. Similar studies were then conducted with purified, intact muOPR with similar
      results. Combinations of epinephrine with methionine enkephalin or morphine
      increased the binding of both by about half a log unit. These results suggest
      that muOPR may be allosterically enhanced by adrenergic agonists.

PMID- 29342107
TI  - Honokiol Improves Liver Steatosis in Ovariectomized Mice.
AB  - Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease, and is
      associated with the development of metabolic syndrome. Postmenopausal women with
      estrogen deficiency are at a higher risk of progression to NAFLD. Estrogen has a
      protective effect against the progression of the disease. Currently, there are no
      safe and effective treatments for these liver diseases in postmenopausal women.
      Honokiol (Ho), a bioactive natural product derived from Magnolia spp, has anti
      inflammatory, anti-angiogenic, and anti-oxidative properties. In our study, we
      investigated the beneficial effects of Ho on NAFLD in ovariectomized (OVX) mice.
      We divided the mice into four groups, as follows: SHAM, OVX, OVX+beta-estradiol
      (0.4 mg/kg of bodyweight), and OVX+Ho (50 mg/kg of diet). Mice were fed diets
      with/without Ho for 12 weeks. The bodyweight, epidermal fat, and weights of liver
      tissue were lower in the OVX group than in the other groups. Ho improved hepatic
      steatosis and reduced proinflammatory cytokine levels. Moreover, Ho markedly
      downregulated plasma lipid levels. Our results indicate that Ho ameliorated OVX
      induced fatty liver and inflammation, as well as associated lipid metabolism.
      These findings suggest that Ho may be hepatoprotective against NAFLD in
      postmenopausal women.

PMID- 29342108
TI  - Different Lipid Regulation in Ovarian Cancer: Inhibition of the Immune System.
AB  - Lipid metabolism is altered in several cancer settings leading to different
      ratios of intermediates. Ovarian cancer is the most lethal gynecological
      malignancy. Cancer cells disperse in the abdominal space and ascites occurs. T
      cells obtained from ascites are unable to proliferate after an antigenic
      stimulus. The proliferation of ascites-derived T cells can be restored after
      culturing the cells for ten days in normal culture medium. No pathway aberrancies
      were detected. The acellular fraction of ascites can inhibit the proliferation of
      autologous as well as allogeneic peripheral blood lymphocytes, indicating the
      presence of soluble factors that interfere with T cell functionality. Therefore,
      we analyzed 109 lipid mediators and found differentially regulated lipids in
      suppressive ascitic fluid compared to normal abdominal fluid. Our study indicates
      the presence of lipid intermediates in ascites of ovarian cancer patients, which
      coincidences with T cell dysfunctionality. Since the immune system in the
      abdominal cavity is compromised, this may explain the high seeding efficiency of
      disseminated tumor cells. Further research is needed to fully understand the
      correlation between the various lipids and T cell proliferation, which could lead
      to new treatment options.

PMID- 29342109
TI  - Sources of Added Sugars in Young Children, Adolescents, and Adults with Low and
      High Intakes of Added Sugars.
AB  - High intake of added sugars is associated with excess energy intake and poorer
      diet quality. The objective of this cross-sectional study (n = 16,806) was to
      estimate usual intakes and the primary food sources of added sugars across the
      range of intakes (i.e., deciles) among U.S. children (2-8 years), adolescents and
      teens (9-18 years), and adults (>=19 years) using the National Health and
      Nutrition Examination (NHANES) data from 2009-2012. The percent energy
      contributed by added sugars was 14.3 +/- 0.2% (2-8 years), 16.2 +/- 0.2% (9-18
      years), and 13.1 +/- 0.2% (>=19 years), suggesting the highest intakes are among
      adolescents and teens. However, the primary foods/beverages that contribute to
      added sugars were remarkably consistent across the range of intakes, with the
      exception of the lowest decile, and include sweetened beverages and sweet bakery
      products. Interestingly across all age groups, even those in the lowest decile of
      added sugars exceed the 10% guidelines. Additional foods contributing to high
      intakes were candy and other desserts (e.g., ice cream) in children and
      adolescents, and coffee and teas in adults. Tailoring public health messaging to
      reduce intakes of these identified food groups may be of utility in designing
      effective strategies to reduce added sugar intake in the U.S.

PMID- 29342110
TI  - Medlay: A Reconfigurable Micro-Power Management to Investigate Self-Powered
      Systems.
AB  - In self-powered microsystems, a power management is essential to extract,
      transfer and regulate power from energy harvesting sources to loads such as
      sensors. The challenge is to consider all of the different structures and
      components available and build the optimal power management on a microscale. The
      purpose of this paper is to streamline the design process by creating a novel
      reconfigurable testbed called Medlay. First, we propose a uniform interface for
      management functions e.g., power conversion, energy storing and power routing.
      This interface results in a clear layout because power and status pins are
      strictly separated, and inputs and outputs have fixed positions. Medlay is the
      ready-to-use and open-hardware platform based on the interface. It consists of a
      base board and small modules incorporating e.g., dc-dc converters, power switches
      and supercapacitors. Measurements confirm that Medlay represents a system on one
      circuit board, as parasitic effects of the interconnections are negligible. The
      versatility regarding different setups on the testbed is determined to over
      250,000 combinations by layout graph grammar. Lastly, we underline the
      applicability by recreating three state-of-the-art systems with the testbed. In
      conclusion, Medlay facilitates building and testing power management in a very
      compact, clear and extensible fashion.

PMID- 29342111
TI  - Cytotoxicity Evaluation of Turmeric Extract Incorporated Oil-in-Water
      Nanoemulsion.
AB  - To overcome the drawbacks of conventional drug delivery system, nanoemulsion have
      been developed as an advanced form for improving the delivery of active
      ingredients. However, safety evaluation is crucial during the development stage
      before the commercialization. Therefore, the aim of this study was to evaluate
      the cytotoxicity of two types of newly developed nanoemulsions. Turmeric extract
      loaded nanoemulsion powder-10.6 (TE-NEP-10.6, high content of artificial
      surfactant Tween 80), which forms the optimal nanoemulsion, and the TE-NEP-8.6
      made by increasing the content of natural emulsifier (lecithin) to reduce the
      potential toxicity of nanoemulsion were cultured with various cells (NIH3T3,
      H9C2, HepG2, hCPC, and hEPC) and the changes of each cell were observed followed
      by nanoemulsion treatment. As a result, the two nanoemulsions (TE-NEP-10.6 and TE
      NEP-8.6) did not show significant difference in cell viability. In the case of
      cell line (NIH3T3, H9C2, and HepG2), toxicity was not observed at an experimental
      concentration of less than 1 mg/mL, however, the cell survival rate decreased in
      a concentration dependent manner in the case of primary cultured cells. These
      results from our study can be used as a basic data to confirm the cell type
      dependent toxicity of nanoemulsion.

PMID- 29342112
TI  - Useful Bicistronic Reporter System for Studying Poly(A) Site-Defining cis
      Elements and Regulation of Alternative Polyadenylation.
AB  - The link between polyadenylation (pA) and various biological, behavioral, and
      pathological events of eukaryotes underlines the need to develop in vivo
      polyadenylation assay methods for characterization of the cis-acting elements,
      trans-acting factors and environmental stimuli that affect polyadenylation
      efficiency and/or relative usage of two alternative polyadenylation (APA) sites.
      The current protein-based CAT or luciferase reporter systems can measure the
      polyadenylation efficiency of a single pA site or candidate cis element but not
      the choice of two APA sites. To address this issue, we developed a set of four
      new bicistronic reporter vectors that harbor either two luciferase or
      fluorescence protein open reading frames connected with one Internal Ribosome
      Entry Site (IRES). Transfection of single or dual insertion constructs of these
      vectors into mammalian cells demonstrated that they could be utilized not only to
      quantify the strength of a single candidate pA site or cis element, but also to
      accurately measure the relative usage of two APA sites at both the mRNA (qRT-PCR)
      and protein levels. This represents the first reporter system that can study
      polyadenylation efficiency of a single pA site or element and regulation of two
      APA sites at both the mRNA and protein levels.

PMID- 29342114
TI  - GaN-Based Laser Wireless Power Transfer System.
AB  - The aim of this work is to present a potential application of gallium nitride
      based optoelectronic devices. By using a laser diode and a photodetector, we
      designed and demonstrated a free-space compact and lightweight wireless power
      transfer system, whose efficiency is limited by the efficiency of the receiver.
      We analyzed the effect of the electrical load, temperature, partial absorption
      and optical excitation distribution on the efficiency, by identifying heating and
      band-filling as the most impactful processes. By comparing the final demonstrator
      with a commercial RF-based Qi system, we conclude that the efficiency is still
      low at close range, but is promising in medium to long range applications.
      Efficiency may not be a limiting factor, since this concept can enable entirely
      new possibilities and designs, especially relevant for space applications.

PMID- 29342113
TI  - Mitochondria, Oxidative Stress and the Kynurenine System, with a Focus on Ageing
      and Neuroprotection.
AB  - In this review, the potential causes of ageing are discussed. We seek to gain
      insight into the main physiological functions of mitochondria and discuss
      alterations in their function and the genome, which are supposed to be the
      central mechanisms in senescence. We conclude by presenting the potential
      modulating role of the kynurenine pathway in the ageing processes. Mitochondrial
      dynamics are supposed to have important physiological roles in maintaining cell
      homeostasis. During ageing, a decrease in mitochondrial dynamics was reported,
      potentially compromising the function of mitochondria. Mitochondrial biogenesis
      not only encompasses mitochondrial dynamics, but also the regulation of
      transcription and translation of genes, and mitochondria are supposed to play a
      prominent role in cell death during senescence. Defects in the mtDNA replication
      machinery and failure in the repair of mtDNA might result in the accumulation of
      mutations, leading to mitochondrial dysfunction and bioenergetic failure of the
      cell. The role of reactive oxygen species (ROS) in the ageing processes is widely
      acknowledged. Exaggerated oxidative damage to mDNA is supposed to take place
      during senescence, including single-nucleotide base alterations, nucleotide base
      pair alterations, chain breaks and cross linkage. A broad repertoire for the
      repair of DNA faults has evolved, but they do not function efficiently during
      senescence. Poly (ADP-ribose) polymerase (PARP) is an enzyme that assists in DNA
      repair, i.e., it participates in the repair of single-stranded DNA nicks,
      initiating base excision repair (BER). In the case of extensive DNA damage, PARP
      1 becomes overactivated and rapidly depletes the intracellular NAD+ and ATP
      pools. This results in a profound energy loss of the cell and leads to cell
      dysfunction, or even cell death. Alterations in the kynurenine system have been
      linked with ageing processes and several age-related disorders. The kynurenine
      pathway degrades tryptophan (TRP) to several metabolites, among others kynurenine
      (KYN), kynurenic acid (KYNA) and quinolinic acid (QUIN). The end product of the
      route is NAD+. The first metabolic reaction is mediated by TRP-2,3-dioxygenase
      (TDO) or indolamine-2,3-dioxygenases (IDO), the latter being induced by
      inflammation, and it is thought to have a significant role in several disorders
      and in ageing. Research is currently focusing on the KYN pathway, since several
      intermediates possess neuro- and immunoactive properties, and hence are capable
      of modulating the activity of certain brain cells and inflammatory responses.
      During ageing, and in many age-associated disorders like obesity, dyslipidaemia,
      hypertension, insulin resistance and neurodegenerative diseases, low-grade,
      sustained inflammation and upregulation of IDO have been reported. However, TRP
      downstream catabolites create a negative feedback loop by weakening the activated
      immune system through several actions, including a decline in the Th1 response
      and an enhancement of Th2-type processes. The broad actions of the KYN
      intermediates in brain excitation/inhibition and their role in regulating immune
      responses may provide the possibility of modifying the pathological processes in
      an array of age-associated diseases in the future.

PMID- 29342115
TI  - Investigating the Associations between Ethnic Networks, Community Social Capital,
      and Physical Health among Marriage Migrants in Korea.
AB  - This study examines factors associated with the physical health of Korea's
      growing immigrant population. Specifically, it focuses on the associations
      between ethnic networks, community social capital, and self-rated health (SRH)
      among female marriage migrants. For empirical testing, secondary analysis of a
      large nationally representative sample (NSMF 2009) is conducted. Given the
      clustered data structure (individuals nested in communities), a series of two
      level random intercepts and slopes models are fitted to probe the relationships
      between SRH and interpersonal (bonding and bridging) networks among foreign-born
      wives in Korea. In addition to direct effects, cross-level interaction effects
      are investigated using hierarchical linear modeling. While adjusting for
      confounders, bridging (inter-ethnic) networks are significantly linked with
      better health. Bonding (co-ethnic) networks, to the contrary, are negatively
      associated with immigrant health. Net of individual-level covariates, living in a
      commuijnity with more aggregate bridging social capital is positively linked with
      health. Community-level bonding social capital, however, is not a significant
      predictor. Lastly, two cross-level interaction terms are found. First, the
      positive relationship between bridging network and health is stronger in
      residential contexts with more aggregate bridging social capital. Second, it is
      weaker in communities with more aggregate bonding social capital.

PMID- 29342117
TI  - Assessment of TSPO in a Rat Experimental Autoimmune Myocarditis Model: A
      Comparison Study between [18F]Fluoromethyl-PBR28 and [18F]CB251.
AB  - Overexpression of the 18-kDa translocator protein (TSPO) is closely linked to
      inflammatory responses in the heart, including myocarditis, which can lead to
      myocardial necrosis. In vivo assessment of inflammatory responses has enabled the
      precise diagnosis of myocarditis to improve clinical outcomes. Here, we evaluated
      TSPO overexpression in a rat model of experimental autoimmune myocarditis (EAM)
      compared to healthy rats using two TSPO radiotracers, [18F]fluoromethyl-PBR28
      ([18F]1) and [18F]CB251 ([18F]2). All radiolabeling methods were successfully
      applied to an automated module for the reproducible preparation of TSPO
      radiotracers. Both radiotracers were directly compared in an EAM rat model, as
      well as in healthy rats to determine whether either radiotracer provides a more
      promising assessment of in vivo TSPO overexpression. [18F]2 provided more
      specific TSPO-uptake in the heart of the EAM rats (1.32-fold that of the heart-to
      lung uptake ratio versus healthy controls), while [18F]1 did not show a
      significant difference between the two groups. Histopathological characterization
      revealed that a prominent positron emission tomography (PET) signal of [18F]2 in
      the EAM rats corresponded to the presence of a higher density of TSPO compared to
      the healthy controls. These results suggest that the imidazole[1,2-a]pyridine
      based radiotracer [18F]2 is a sensitive tool for noninvasively diagnosing
      myocarditis related to inflammation of the heart muscle by assessing abnormal
      TSPO expression.

PMID- 29342118
TI  - Microbial Degradation Behavior in Seawater of Polyester Blends Containing Poly(3
      hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx).
AB  - The microbial degradation behavior of poly(3-hydroxybutyrate-co-3
      hydroxyhexanoate) (PHBHHx) and its compound with several polyesters such as
      poly(butylene adipate-co-telephtharate) (PBAT), poly(butylene succinate) (PBS),
      and polylactic acid (PLA) in seawater was tested by a biological oxygen demand
      (BOD) method. PHBHHx showed excellent biodegradation in seawater in this study.
      In addition, the biodegradation rate of several blends was much influenced by the
      weight ratio of PHBHHx in their blends and decreased in accordance with the
      decrement of PHBHHX ratio. The surface morphology of the sheet was important
      factor for controlling the biodegradation rate of PHBHHx-containing blends in
      seawater.

PMID- 29342119
TI  - Novel Hybrid Formulations Based on Thiourea Derivatives and Core@Shell Fe3O4@C18
      Nanostructures for the Development of Antifungal Strategies.
AB  - The continuously increasing global impact of fungal infections is requiring the
      rapid development of novel antifungal agents. Due to their multiple
      pharmacological activities, thiourea derivatives represent privileged candidates
      for shaping new drugs. We report here the preparation, physico-chemical
      characterization and bioevaluation of hybrid nanosystems based on new 2-((4
      chlorophenoxy)methyl)-N-(substituted phenylcarbamo-thioyl)benzamides and
      Fe3O4@C18 core@shell nanoparticles. The new benzamides were prepared by an
      efficient method, then their structure was confirmed by spectral studies and
      elemental analysis and they were further loaded on Fe3O4@C18 nanostructures. Both
      the obtained benzamides and the resulting hybrid nanosystems were tested for
      their efficiency against planktonic and adherent fungal cells, as well as for
      their in vitro biocompatibility, using mesenchymal cells. The antibiofilm
      activity of the obtained benzamides was dependent on the position and nature of
      substituents, demonstrating that structure modulation could be a very useful
      approach to enhance their antimicrobial properties. The hybrid nanosystems have
      shown an increased efficiency in preventing the development of Candida albicans
      (C. albicans) biofilms and moreover, they exhibited a good biocompatibility,
      suggesting that Fe3O4@C18core@shell nanoparticles could represent promising
      nanocarriers for antifungal substances, paving the way to the development of
      novel effective strategies with prophylactic and therapeutic value for fighting
      biofilm associated C. albicans infections.

PMID- 29342116
TI  - VEGF Signaling in Neurological Disorders.
AB  - Vascular endothelial growth factor (VEGF) is a potent growth factor playing
      diverse roles in vasculogenesis and angiogenesis. In the brain, VEGF mediates
      angiogenesis, neural migration and neuroprotection. As a permeability factor,
      excessive VEGF disrupts intracellular barriers, increases leakage of the choroid
      plexus endothelia, evokes edema, and activates the inflammatory pathway.
      Recently, we discovered that a heparin binding epidermal growth factor like
      growth factor (HB-EGF)-a class of EGF receptor (EGFR) family ligands-contributes
      to the development of hydrocephalus with subarachnoid hemorrhage through
      activation of VEGF signaling. The objective of this review is to entail a recent
      update on causes of death due to neurological disorders involving cerebrovascular
      and age-related neurological conditions and to understand the mechanism by which
      angiogenesis-dependent pathological events can be treated with VEGF antagonisms.
      The Global Burden of Disease study indicates that cancer and cardiovascular
      disease including ischemic and hemorrhagic stroke are two leading causes of death
      worldwide. The literature suggests that VEGF signaling in ischemic brains
      highlights the importance of concentration, timing, and alternate route of
      modulating VEGF signaling pathway. Molecular targets distinguishing two distinct
      pathways of VEGF signaling may provide novel therapies for the treatment of
      neurological disorders and for maintaining lower mortality due to these
      conditions.

PMID- 29342121
TI  - beta-Escin Effectively Modulates HUVECS Proliferation and Tube Formation.
AB  - In the present study we evaluated the anti-angiogenic activities of beta-escin
      (the major active compound of Aesculus hippocastanum L. seeds). Human umbilical
      vein endothelial cells (HUVECs) were used as an in vitro model for studying the
      molecular mechanism underlying the anti-angiogenic effect of beta-escin. We
      investigated the in vitro effects on proliferation, migration, and tube formation
      of HUVECs and in vivo anti-angiogenic activity was evaluated in a chick
      chorioallantoic membrane (CAM) angiogenesis assay. Moreover, the effect on gene
      expressions was determined by the RT2 ProfilerTM human angiogenesis PCR Array. It
      was found that beta-escin exerts inhibitory effect on the basic fibroblast growth
      factor (bFGF)-induced proliferation, migration and tube formation, as well as CAM
      angiogenesis in vivo. The inhibition of critical steps of angiogenic process
      observed with beta-escin could be partially explained by suppression of Akt
      activation in response to bFGF. Moreover, the anti-angiogenic effects of beta
      escin could also be mediated via inhibition of EFNB2 and FGF-1 gene expressions
      in endothelial cells. In conclusion, beta-escin affects endothelial cells as a
      negative mediator of angiogenesis in vitro and in vivo and may therefore be
      considered as a promising candidate for further research elucidating its
      underlying mechanism of action.

PMID- 29342122
TI  - Synthesis and Characterization of a Heterometallic Extended Architecture Based on
      a Manganese(II)-Substituted Sandwich-Type Polyoxotungstate.
AB  - The reaction of [alpha-P2W15O56]12- with MnII and DyIII in an aqueous basic
      solution led to the isolation of an all inorganic heterometallic aggregate
      Na10(OH2)42[{Dy(H2O)6}2Mn4P4W30O112(H2O)2].17H2O (Dy2Mn4-P2W15). Single-crystal X
      ray diffraction revealed that Dy2Mn4-P2W15 crystallizes in the triclinic system
      with space group P 1 - , and consists of a tetranuclear manganese(II)-substituted
      sandwich-type phosphotungstate [Mn4(H2O)2(P2W15O56)2]16- (Mn4-P2W15), Na, and
      DyIII cations. Compound Dy2Mn4-P2W15 exhibits a 1D ladder-like chain structure
      based on sandwich-type segments and dysprosium cations as linkers, which are
      further connected into a three-dimensional open framework by sodium cations. The
      title compound was structurally and compositionally characterized in solid state
      by single-crystal XRD, powder X-ray diffraction (PXRD), Fourier-transform
      infrared spectroscopy (FTIR), thermogravimetric (TGA), and elemental analyses.
      Further, the absorption and emission electronic spectra in aqueous solutions of
      Dy2Mn4-P2W15 and Mn4-P2W15 were studied. Also, magnetic properties were studied
      and compared with the magnetic behavior of [Mn4(H2O)2(P2W15O56)2]16-.

PMID- 29342123
TI  - Image-Based Localization Aided Indoor Pedestrian Trajectory Estimation Using
      Smartphones.
AB  - Accurately determining pedestrian location in indoor environments using consumer
      smartphones is a significant step in the development of ubiquitous localization
      services. Many different map-matching methods have been combined with pedestrian
      dead reckoning (PDR) to achieve low-cost and bias-free pedestrian tracking.
      However, this works only in areas with dense map constraints and the error
      accumulates in open areas. In order to achieve reliable localization without map
      constraints, an improved image-based localization aided pedestrian trajectory
      estimation method is proposed in this paper. The image-based localization
      recovers the pose of the camera from the 2D-3D correspondences between the 2D
      image positions and the 3D points of the scene model, previously reconstructed by
      a structure-from-motion (SfM) pipeline. This enables us to determine the initial
      location and eliminate the accumulative error of PDR when an image is
      successfully registered. However, the image is not always registered since the
      traditional 2D-to-3D matching rejects more and more correct matches when the
      scene becomes large. We thus adopt a robust image registration strategy that
      recovers initially unregistered images by integrating 3D-to-2D search. In the
      process, the visibility and co-visibility information is adopted to improve the
      efficiency when searching for the correspondences from both sides. The
      performance of the proposed method was evaluated through several experiments and
      the results demonstrate that it can offer highly acceptable pedestrian
      localization results in long-term tracking, with an error of only 0.56 m, without
      the need for dedicated infrastructures.

PMID- 29342124
TI  - The Root of Atractylodes macrocephala Koidzumi Prevents Obesity and Glucose
      Intolerance and Increases Energy Metabolism in Mice.
AB  - Targeting energy expenditure offers a strategy for treating obesity more
      effectively and safely. In previous studies, we found that the root of
      Atractylodes macrocephala Koidzumi (Atractylodis Rhizoma Alba, ARA) increased
      energy metabolism in C2C12 cells. Here, we investigated the effects of ARA on
      obesity and glucose intolerance by examining energy metabolism in skeletal muscle
      and brown fat in high-fat diet (HFD) induced obese mice. ARA decreased body
      weight gain, hepatic lipid levels and serum total cholesterol levels, but did not
      modify food intake. Fasting serum glucose, serum insulin levels and glucose
      intolerance were all improved in ARA treated mice. Furthermore, ARA increased
      peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1alpha)
      expression, and the phosphorylation of adenosine monophosphate-activated protein
      kinase (AMPK) in skeletal muscle tissues, and also prevented skeletal muscle
      atrophy. In addition, the numbers of brown adipocytes and the expressions of
      PGC1alpha and uncoupling protein 1 (UCP1) were elevated in the brown adipose
      tissues of ARA treated mice. Our results show that ARA can prevent diet-induced
      obesity and glucose intolerance in C5BL/6 mice and suggests that the mechanism
      responsible is related to the promotion of energy metabolism in skeletal muscle
      and brown adipose tissues.

PMID- 29342126
TI  - Tailoring Cu Nanoparticle Catalyst for Methanol Synthesis Using the Spinning Disk
      Reactor.
AB  - Cu nanoparticles are known to be very active for methanol (MeOH) synthesis at
      relatively low temperatures, such that smaller particle sizes yield better MeOH
      productivity. We aimed to control Cu nanoparticle (NP) size and size distribution
      for catalysing MeOH synthesis, by using the spinning disk reactor. The spinning
      disk reactor (SDR), which operates based on shear effect and plug flow in thin
      films, can be used to rapidly micro-mix reactants in order to control nucleation
      and particle growth for uniform particle size distribution. This could be
      achieved by varying both physical and chemical operation conditions in a
      precipitation reaction on the SDR. We have used the SDR for a Cu borohydride
      reduction to vary Cu NP size from 3 nm to about 55 nm. XRD and TEM
      characterization confirmed the presence of Cu2O and Cu crystallites when the
      samples were dried. This technique is readily scalable for Cu NP production by
      processing continuously over a longer duration than the small-scale tests.
      However, separation of the nanoparticles from solution posed a challenge as the
      suspension hardly settled. The Cu NPs produced were tested to be active catalyst
      for MeOH synthesis at low temperature and MeOH productivity increased with
      decreasing particle size.

PMID- 29342125
TI  - Induction of Pro-Apoptotic Endoplasmic Reticulum Stress in Multiple Myeloma Cells
      by NEO214, Perillyl Alcohol Conjugated to Rolipram.
AB  - Despite the introduction of new therapies for multiple myeloma (MM), many
      patients are still dying from this disease and novel treatments are urgently
      needed. We have designed a novel hybrid molecule, called NEO214, that was
      generated by covalent conjugation of the natural monoterpene perillyl alcohol
      (POH), an inducer of endoplasmic reticulum (ER) stress, to rolipram (Rp), an
      inhibitor of phosphodiesterase-4 (PDE4). Its potential anticancer effects were
      investigated in a panel of MM cell lines. We found that NEO214 effectively killed
      MM cells in vitro with a potency that was over an order of magnitude stronger
      than that of its individual components, either alone or in combination. The
      cytotoxic mechanism of NEO214 involved severe ER stress and prolonged induction
      of CCAAT/enhancer-binding protein homologous protein (CHOP), a key pro-apoptotic
      component of the ER stress response. These effects were prevented by salubrinal,
      a pharmacologic inhibitor of ER stress, and by CHOP gene knockout. Conversely,
      combination of NEO214 with bortezomib, a drug in clinical use for patients with
      MM, resulted in synergistic enhancement of MM cell death. Combination with the
      adenylate cyclase stimulant forskolin did not enhance NEO214 impact, indicating
      that cyclic adenosine 3',5'-monophosphate (AMP) pathways might play a lesser
      role. Our study introduces the novel agent NEO214 as a potent inducer of ER
      stress with significant anti-MM activity in vitro. It should be further
      investigated as a potential MM therapy aimed at exploiting this tumor's distinct
      sensitivity to ER stress.

PMID- 29342127
TI  - Enhancement in Corneal Permeability of Dissolved Carteolol by Its Combination
      with Magnesium Hydroxide Nanoparticles.
AB  - We prepared magnesium hydroxide (MH) nanoparticles, and investigated their effect
      when combined with dissolved carteolol on the bioavailability and intraocular
      pressure (IOP)-reducing effect of carteolol. The carteolol was solved in saline
      containing additives (0.5% methylcellulose, 0.001% benzalkonium chloride, 0.5%
      mannitol; CRT-solution). MH nanoparticles were prepared by a bead mill method
      with additives. Then carteolol/MH microparticle and carteolol/MH nanoparticle
      fixed combinations (mCMFC and nCMFC) were prepared by mixing the CRT-solution and
      MH particles. The transcorneal penetration and IOP-reducing effect of carteolol
      was evaluated in rabbits. The mean particle size of mCMFC was 7.2 MUm, and the
      particle size was reduced to 73.5-113.5 nm by the bead mill treatment. The MH
      particles in nCMFC remained in the nano size range for 8 days after preparation,
      and the amounts of lacrimal fluid and corneal damage were unchanged by repetitive
      instillation of nCMFC (twice a day for 4 weeks). The transcorneal penetration of
      carteolol was enhanced by the combination with MH nanoparticles, and the IOP
      reducing effect of nCMFC was significantly higher than that of CRT-solution or
      mCMFC. In conclusion, we designed nCMFC, and showed that the high levels of
      dissolved carteolol can be delivered into the aqueous humor by the instillation
      of nCMFC. Combination with MH nanoparticles may achieve an enhancement of corneal
      penetration for water-soluble drugs. These findings provide significant
      information that can be used to design further studies aimed at developing anti
      glaucoma eye drugs.

PMID- 29342128
TI  - The Effect of Emulsion Intensity on Selected Sensory and Instrumental Texture
      Properties of Full-Fat Mayonnaise.
AB  - Varying processing conditions can strongly affect the microstructure of
      mayonnaise, opening up new applications for the creation of products tailored to
      meet different consumer preferences. The aim of the study was to evaluate the
      effect of emulsification intensity on sensory and instrumental characteristics of
      full-fat mayonnaise. Mayonnaise, based on a standard recipe, was processed at low
      and high emulsification intensities, with selected sensory and instrumental
      properties then evaluated using an analytical panel and a back extrusion method.
      The evaluation also included a commercial reference mayonnaise. The overall
      effects of a higher emulsification intensity on the sensory and instrumental
      characteristics of full-fat mayonnaise were limited. However, texture was
      affected, with a more intense emulsification resulting in a firmer mayonnaise
      according to both back extrusion data and the analytical sensory panel.
      Appearance, taste and flavor attributes were not affected by processing.

PMID- 29342129
TI  - Fabrication, Structural Characterization and Uniaxial Tensile Properties of Novel
      Sintered Multi-Layer Wire Mesh Porous Plates.
AB  - There is an increasing interest in developing porous metals or metallic foams for
      functional and structural applications. The study of the physical and mechanical
      properties of porous metals is very important and helpful for their application.
      In this paper, a novel sintered multilayer wire mesh porous plate material
      (WMPPs) with a thickness of 0.5 mm-3 mm and a porosity of 10-35% was prepared by
      winding, pressing, rolling, and subsequently vacuum sintering them. The pore size
      and total size distribution in the as-prepared samples were investigated using
      the bubble point method. The uniaxial tensile behavior of the WMPPs was
      investigated in terms of the sintering temperature, porosity, wire diameter, and
      manufacturing technology. The deformation process and the failure mechanism under
      the tensile press was also discussed based on the appearance of the fractures
      (SEM figures). The results indicated that the pore size and total size
      distribution were closely related to the raw material used and the sintering
      temperature. For the WMPPs prepared by the wire mesh, the pore structures were
      inerratic and the vast majority of pore size was less than 10 MUm. On the other
      hand, for the WMPPs that were prepared by wire mesh and powder, the pore
      structures were irregular and the pore size ranged from 0 MUm-50 MUm. The
      experimental data showed that the tensile strength of WMPPs is much higher than
      any other porous metals or metallic foams. Higher sintering temperatures led to
      coarser joints between wires and resulted in higher tensile strength. The
      sintering temperature decreased from 1330  degrees C to 1130  degrees C and the
      tensile strength decreased from 296 MPa to 164 MPa. Lower porosity means that
      there are more metallurgical joints and metallic frameworks resisting deformation
      per unit volume. Therefore, lower porosities exhibit higher tensile strength. An
      increase of porosity from 17.14% to 32.5% led to the decrease of the tensile
      strength by 90 MPa. The coarser wires led to a bigger contact area between the
      interconnecting wires, resulting in a stronger sintering neck that exhibited
      higher tensile strength. The wire diameter increased from 81 MUm to 122 MUm and
      the tensile strength increased from 296 MPa to 362 MPa. The fracture morphology
      showed that the wires experience necking deformation and ductile fracture.

PMID- 29342130
TI  - Thyroid-Stimulating Hormone Levels Are Positively Associated with Insulin
      Resistance.
AB  - BACKGROUND It has been reported that overt and mild thyroid dysfunctions are
      associated with insulin resistance (IR). We performed this retrospective study to
      evaluate the relationships between thyroid-stimulating hormone (TSH) levels
      within the reference range and IR. MATERIAL AND METHODS A total of 447
      outpatients were enrolled in this study: 298 with type 2 diabetes mellitus and
      149 nondiabetic individuals. Based on a cutoff HbA1c value of 7%, diabetic
      patients were additionally divided into 2 groups: a high-HbA1c group (n=240) and
      a low-HbA1c group (n=58). The relationships of TSH levels and HOMA-IR were
      computed using linear regression models. RESULTS TSH levels were positively and
      linearly associated with HOMA-IR in both the nondiabetic and diabetic groups
      (r=0.210, p=0.011 and r=0.451, p<0.001), as well as in the high- and low-HbA1c
      groups (r=0.507, p<0.001 and r=0.259, p=0.048). A better correlation between TSH
      levels and HOMA-IR was found in the diabetic group and in the high-HbA1c group
      when compared with the nondiabetic group and the low-HbA1c group, respectively.
      Linear regression analysis showed that TSH levels were independently associated
      with HOMA-IR (p=0.034, =0.049 and <0.001 in nondiabetic, low-, and high-HbA1c
      groups, respectively). CONCLUSIONS Our data suggest that TSH is independently
      associated with insulin resistance.

PMID- 29342131
TI  - Survey of plasma proteins in children with progeria pre-therapy and on-therapy
      with lonafarnib.
AB  - BackgroundHutchinson-Gilford progeria syndrome (HGPS) is an ultra-rare, fatal,
      segmental premature aging syndrome caused by the aberrant lamin A protein,
      progerin. The protein farnesyltransferase inhibitor, lonafarnib, ameliorates some
      aspects of cardiovascular and bone disease.MethodsWe performed a prospective
      longitudinal survey of plasma proteins in 24 children with HGPS (an estimated 10%
      of the world's population at the time) at baseline and on lonafarnib therapy,
      compared with age- and gender-matched controls using a multi-analyte, microsphere
      based immunofluorescent assay.ResultsThe mean levels for 23/66 (34.8%) proteins
      were significantly lower and 7/66 (10.6%) were significantly higher in HGPS
      samples compared with those in controls (P<=0.05). Six proteins whose
      concentrations were initially lower normalized with lonafarnib therapy:
      interleukins 1alpha, 7, and 13, beta-2 microglobulin, C-reactive protein, and
      myoglobin. Alpha-2 macroglobulin, a protease inhibitor associated with stroke,
      was elevated at baseline and subsequently normalized with lonafarnib
      therapy.ConclusionThis is the first study to employ a multi-analyte array
      platform in HGPS. Novel potential biomarkers identified in this study should be
      further validated by correlations with clinical disease status, especially
      proteins associated with cardiovascular disease and those that normalized with
      lonafarnib therapy.

PMID- 29342132
TI  - Centimetre-scale electron diffusion in photoactive organic heterostructures.
AB  - The unique properties of organic semiconductors, such as flexibility and
      lightness, are increasingly important for information displays, lighting and
      energy generation. But organics suffer from both static and dynamic disorder, and
      this can lead to variable-range carrier hopping, which results in notoriously
      poor electrical properties, with low electron and hole mobilities and
      correspondingly short charge-diffusion lengths of less than a micrometre. Here we
      demonstrate a photoactive (light-responsive) organic heterostructure comprising a
      thin fullerene channel sandwiched between an electron-blocking layer and a
      blended donor:C70 fullerene heterojunction that generates charges by dissociating
      excitons. Centimetre-scale diffusion of electrons is observed in the fullerene
      channel, and this can be fitted with a simple electron diffusion model. Our
      experiments enable the direct measurement of charge diffusivity in organic
      semiconductors, which is as high as 0.83 +/- 0.07 square centimetres per second
      in a C60 channel at room temperature. The high diffusivity of the fullerene
      combined with the extraordinarily long charge-recombination time yields diffusion
      lengths of more than 3.5 centimetres, orders of magnitude larger than expected
      for an organic system.

PMID- 29342133
TI  - A Myc enhancer cluster regulates normal and leukaemic haematopoietic stem cell
      hierarchies.
AB  - The transcription factor Myc is essential for the regulation of haematopoietic
      stem cells and progenitors and has a critical function in haematopoietic
      malignancies. Here we show that an evolutionarily conserved region located 1.7
      megabases downstream of the Myc gene that has previously been labelled as a
      'super-enhancer' is essential for the regulation of Myc expression levels in both
      normal haematopoietic and leukaemic stem cell hierarchies in mice and humans.
      Deletion of this region in mice leads to a complete loss of Myc expression in
      haematopoietic stem cells and progenitors. This caused an accumulation of
      differentiation-arrested multipotent progenitors and loss of myeloid and B cells,
      mimicking the phenotype caused by Mx1-Cre-mediated conditional deletion of the
      Myc gene in haematopoietic stem cells. This super-enhancer comprises multiple
      enhancer modules with selective activity that recruits a compendium of
      transcription factors, including GFI1b, RUNX1 and MYB. Analysis of mice carrying
      deletions of individual enhancer modules suggests that specific Myc expression
      levels throughout most of the haematopoietic hierarchy are controlled by the
      combinatorial and additive activity of individual enhancer modules, which
      collectively function as a 'blood enhancer cluster' (BENC). We show that BENC is
      also essential for the maintenance of MLL-AF9-driven leukaemia in mice.
      Furthermore, a BENC module, which controls Myc expression in mouse haematopoietic
      stem cells and progenitors, shows increased chromatin accessibility in human
      acute myeloid leukaemia stem cells compared to blasts. This difference correlates
      with MYC expression and patient outcome. We propose that clusters of enhancers,
      such as BENC, form highly combinatorial systems that allow precise control of
      gene expression across normal cellular hierarchies and which also can be hijacked
      in malignancies.

PMID- 29342134
TI  - Chromosomal instability drives metastasis through a cytosolic DNA response.
AB  - Chromosomal instability is a hallmark of cancer that results from ongoing errors
      in chromosome segregation during mitosis. Although chromosomal instability is a
      major driver of tumour evolution, its role in metastasis has not been
      established. Here we show that chromosomal instability promotes metastasis by
      sustaining a tumour cell-autonomous response to cytosolic DNA. Errors in
      chromosome segregation create a preponderance of micronuclei whose rupture spills
      genomic DNA into the cytosol. This leads to the activation of the cGAS-STING
      (cyclic GMP-AMP synthase-stimulator of interferon genes) cytosolic DNA-sensing
      pathway and downstream noncanonical NF-kappaB signalling. Genetic suppression of
      chromosomal instability markedly delays metastasis even in highly aneuploid
      tumour models, whereas continuous chromosome segregation errors promote cellular
      invasion and metastasis in a STING-dependent manner. By subverting lethal
      epithelial responses to cytosolic DNA, chromosomally unstable tumour cells co-opt
      chronic activation of innate immune pathways to spread to distant organs.

PMID- 29342135
TI  - Structures of beta-klotho reveal a 'zip code'-like mechanism for endocrine FGF
      signalling.
AB  - Canonical fibroblast growth factors (FGFs) activate FGF receptors (FGFRs) through
      paracrine or autocrine mechanisms in a process that requires cooperation with
      heparan sulfate proteoglycans, which function as co-receptors for FGFR
      activation. By contrast, endocrine FGFs (FGF19, FGF21 and FGF23) are circulating
      hormones that regulate critical metabolic processes in a variety of tissues.
      FGF19 regulates bile acid synthesis and lipogenesis, whereas FGF21 stimulates
      insulin sensitivity, energy expenditure and weight loss. Endocrine FGFs signal
      through FGFRs in a manner that requires klothos, which are cell-surface proteins
      that possess tandem glycosidase domains. Here we describe the crystal structures
      of free and ligand-bound beta-klotho extracellular regions that reveal the
      molecular mechanism that underlies the specificity of FGF21 towards beta-klotho
      and demonstrate how the FGFR is activated in a klotho-dependent manner. beta
      Klotho serves as a primary 'zip code'-like receptor that acts as a targeting
      signal for FGF21, and FGFR functions as a catalytic subunit that mediates
      intracellular signalling. Our structures also show how the sugar-cutting enzyme
      glycosidase has evolved to become a specific receptor for hormones that regulate
      metabolic processes, including the lowering of blood sugar levels. Finally, we
      describe an agonistic variant of FGF21 with enhanced biological activity and
      present structural insights into the potential development of therapeutic agents
      for diseases linked to endocrine FGFs.

PMID- 29342136
TI  - Clonal evolution mechanisms in NT5C2 mutant-relapsed acute lymphoblastic
      leukaemia.
AB  - Relapsed acute lymphoblastic leukaemia (ALL) is associated with resistance to
      chemotherapy and poor prognosis. Gain-of-function mutations in the 5'
      nucleotidase, cytosolic II (NT5C2) gene induce resistance to 6-mercaptopurine and
      are selectively present in relapsed ALL. Yet, the mechanisms involved in NT5C2
      mutation-driven clonal evolution during the initiation of leukaemia, disease
      progression and relapse remain unknown. Here we use a conditional-and-inducible
      leukaemia model to demonstrate that expression of NT5C2(R367Q), a highly
      prevalent relapsed-ALL NT5C2 mutation, induces resistance to chemotherapy with 6
      mercaptopurine at the cost of impaired leukaemia cell growth and leukaemia
      initiating cell activity. The loss-of-fitness phenotype of NT5C2+/R367Q mutant
      cells is associated with excess export of purines to the extracellular space and
      depletion of the intracellular purine-nucleotide pool. Consequently, blocking
      guanosine synthesis by inhibition of inosine-5'-monophosphate dehydrogenase
      (IMPDH) induced increased cytotoxicity against NT5C2-mutant leukaemia
      lymphoblasts. These results identify the fitness cost of NT5C2 mutation and
      resistance to chemotherapy as key evolutionary drivers that shape clonal
      evolution in relapsed ALL and support a role for IMPDH inhibition in the
      treatment of ALL.

PMID- 29342137
TI  - Corrigendum: mTORC1-dependent AMD1 regulation sustains polyamine metabolism in
      prostate cancer.
AB  - This corrects the article DOI: 10.1038/nature22964.

PMID- 29342138
TI  - alpha-Klotho is a non-enzymatic molecular scaffold for FGF23 hormone signalling.
AB  - The ageing suppressor alpha-klotho binds to the fibroblast growth factor receptor
      (FGFR). This commits FGFR to respond to FGF23, a key hormone in the regulation of
      mineral ion and vitamin D homeostasis. The role and mechanism of this co-receptor
      are unknown. Here we present the atomic structure of a 1:1:1 ternary complex that
      consists of the shed extracellular domain of alpha-klotho, the FGFR1c ligand
      binding domain, and FGF23. In this complex, alpha-klotho simultaneously tethers
      FGFR1c by its D3 domain and FGF23 by its C-terminal tail, thus implementing FGF23
      FGFR1c proximity and conferring stability. Dimerization of the stabilized ternary
      complexes and receptor activation remain dependent on the binding of heparan
      sulfate, a mandatory cofactor of paracrine FGF signalling. The structure of alpha
      klotho is incompatible with its purported glycosidase activity. Thus, shed alpha
      klotho functions as an on-demand non-enzymatic scaffold protein that promotes
      FGF23 signalling.

PMID- 29342139
TI  - Structure and mutagenesis reveal essential capsid protein interactions for KSHV
      replication.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) causes Kaposi's sarcoma, a cancer
      that commonly affects patients with AIDS and which is endemic in sub-Saharan
      Africa. The KSHV capsid is highly pressurized by its double-stranded DNA genome,
      as are the capsids of the eight other human herpesviruses. Capsid assembly and
      genome packaging of herpesviruses are prone to interruption and can therefore be
      targeted for the structure-guided development of antiviral agents. However,
      herpesvirus capsids-comprising nearly 3,000 proteins and over 1,300 A in diameter
      present a formidable challenge to atomic structure determination and functional
      mapping of molecular interactions. Here we report a 4.2 A resolution structure of
      the KSHV capsid, determined by electron-counting cryo-electron microscopy, and
      its atomic model, which contains 46 unique conformers of the major capsid protein
      (MCP), the smallest capsid protein (SCP) and the triplex proteins Tri1 and Tri2.
      Our structure and mutagenesis results reveal a groove in the upper domain of the
      MCP that contains hydrophobic residues that interact with the SCP, which in turn
      crosslinks with neighbouring MCPs in the same hexon to stabilize the capsid.
      Multiple levels of MCP-MCP interaction-including six sets of stacked hairpins
      lining the hexon channel, disulfide bonds across channel and buttress domains in
      neighbouring MCPs, and an interaction network forged by the N-lasso domain and
      secured by the dimerization domain-define a robust capsid that is resistant to
      the pressure exerted by the enclosed genome. The triplexes, each composed of two
      Tri2 molecules and a Tri1 molecule, anchor to the capsid floor via a Tri1 N
      anchor to plug holes in the MCP network and rivet the capsid floor. These
      essential roles of the MCP N-lasso and Tri1 N-anchor are verified by serial
      truncation mutageneses. Our proof-of-concept demonstration of the use of
      polypeptides that mimic the smallest capsid protein to inhibit KSHV lytic
      replication highlights the potential for exploiting the interaction hotspots
      revealed in our atomic structure to develop antiviral agents.

PMID- 29342140
TI  - Atomic structure of the eukaryotic intramembrane RAS methyltransferase ICMT.
AB  - The maturation of RAS GTPases and approximately 200 other cellular CAAX proteins
      involves three enzymatic steps: addition of a farnesyl or geranylgeranyl prenyl
      lipid to the cysteine (C) in the C-terminal CAAX motif, proteolytic cleavage of
      the AAX residues and methylation of the exposed prenylcysteine residue at its
      terminal carboxylate. This final step is catalysed by isoprenylcysteine carboxyl
      methyltransferase (ICMT), a eukaryote-specific integral membrane enzyme that
      resides in the endoplasmic reticulum. ICMT is the only cellular enzyme that is
      known to methylate prenylcysteine substrates; methylation is important for the
      biological functions of these substrates, such as the membrane localization and
      subsequent activity of RAS, prelamin A and RAB. Inhibition of ICMT has potential
      for combating progeria and cancer. Here we present an X-ray structure of ICMT, in
      complex with its cofactor, an ordered lipid molecule and a monobody inhibitor, at
      2.3 A resolution. The active site spans cytosolic and membrane-exposed regions,
      indicating distinct entry routes for the cytosolic methyl donor, S-adenosyl-l
      methionine, and for prenylcysteine substrates, which are associated with the
      endoplasmic reticulum membrane. The structure suggests how ICMT overcomes the
      topographical challenge and unfavourable energetics of bringing two reactants
      that have different cellular localizations together in a membrane environment-a
      relatively uncharacterized but defining feature of many integral membrane
      enzymes.

PMID- 29342141
TI  - Monitoring T cell-dendritic cell interactions in vivo by intercellular enzymatic
      labelling.
AB  - Interactions between different cell types are essential for multiple biological
      processes, including immunity, embryonic development and neuronal signalling.
      Although the dynamics of cell-cell interactions can be monitored in vivo by
      intravital microscopy, this approach does not provide any information on the
      receptors and ligands involved or enable the isolation of interacting cells for
      downstream analysis. Here we describe a complementary approach that uses
      bacterial sortase A-mediated cell labelling across synapses of immune cells to
      identify receptor-ligand interactions between cells in living mice, by generating
      a signal that can subsequently be detected ex vivo by flow cytometry. We call
      this approach for the labelling of 'kiss-and-run' interactions between immune
      cells 'Labelling Immune Partnerships by SorTagging Intercellular Contacts'
      (LIPSTIC). Using LIPSTIC, we show that interactions between dendritic cells and
      CD4+ T cells during T-cell priming in vivo occur in two distinct modalities: an
      early, cognate stage, during which CD40-CD40L interactions occur specifically
      between T cells and antigen-loaded dendritic cells; and a later, non-cognate
      stage during which these interactions no longer require prior engagement of the T
      cell receptor. Therefore, LIPSTIC enables the direct measurement of dynamic cell
      cell interactions both in vitro and in vivo. Given its flexibility for use with
      different receptor-ligand pairs and a range of detectable labels, we expect that
      this approach will be of use to any field of biology requiring quantification of
      intercellular communication.

PMID- 29342142
TI  - Midbrain circuits that set locomotor speed and gait selection.
AB  - Locomotion is a fundamental motor function common to the animal kingdom. It is
      implemented episodically and adapted to behavioural needs, including exploration,
      which requires slow locomotion, and escape behaviour, which necessitates faster
      speeds. The control of these functions originates in brainstem structures,
      although the neuronal substrate(s) that support them have not yet been
      elucidated. Here we show in mice that speed and gait selection are controlled by
      glutamatergic excitatory neurons (GlutNs) segregated in two distinct midbrain
      nuclei: the cuneiform nucleus (CnF) and the pedunculopontine nucleus (PPN).
      GlutNs in both of these regions contribute to the control of slower, alternating
      gait locomotion, whereas only GlutNs in the CnF are able to elicit high-speed,
      synchronous-gait locomotion. Additionally, both the activation dynamics and the
      input and output connectivity matrices of GlutNs in the PPN and the CnF support
      explorative and escape locomotion, respectively. Our results identify two regions
      in the midbrain that act in conjunction to select context-dependent locomotor
      behaviours.

PMID- 29342144
TI  - Erratum: Moving beyond microbiome-wide associations to causal microbe
      identification.
AB  - This corrects the article DOI: 10.1038/nature25019.

PMID- 29342143
TI  - Regulation of embryonic haematopoietic multipotency by EZH1.
AB  - All haematopoietic cell lineages that circulate in the blood of adult mammals
      derive from multipotent haematopoietic stem cells (HSCs). By contrast, in the
      blood of mammalian embryos, lineage-restricted progenitors arise first,
      independently of HSCs, which only emerge later in gestation. As best defined in
      the mouse, 'primitive' progenitors first appear in the yolk sac at 7.5 days post
      coitum. Subsequently, erythroid-myeloid progenitors that express fetal
      haemoglobin, as well as fetal lymphoid progenitors, develop in the yolk sac and
      the embryo proper, but these cells lack HSC potential. Ultimately, 'definitive'
      HSCs with long-term, multilineage potential and the ability to engraft irradiated
      adults emerge at 10.5 days post-coitum from arterial endothelium in the aorta
      gonad-mesonephros and other haemogenic vasculature. The molecular mechanisms of
      this reverse progression of haematopoietic ontogeny remain unexplained. We
      hypothesized that the definitive haematopoietic program might be actively
      repressed in early embryogenesis through epigenetic silencing, and that
      alleviating this repression would elicit multipotency in otherwise lineage
      restricted haematopoietic progenitors. Here we show that reduced expression of
      the Polycomb group protein EZH1 enhances multi-lymphoid output from human
      pluripotent stem cells. In addition, Ezh1 deficiency in mouse embryos results in
      precocious emergence of functional definitive HSCs in vivo. Thus, we identify
      EZH1 as a repressor of haematopoietic multipotency in the early mammalian embryo.

PMID- 29342145
TI  - The gram-negative bacterial periplasm: Size matters.
AB  - Gram-negative bacteria are surrounded by two membrane bilayers separated by a
      space termed the periplasm. The periplasm is a multipurpose compartment separate
      from the cytoplasm whose distinct reducing environment allows more efficient and
      diverse mechanisms of protein oxidation, folding, and quality control. The
      periplasm also contains structural elements and important environmental sensing
      modules, and it allows complex nanomachines to span the cell envelope. Recent
      work indicates that the size or intermembrane distance of the periplasm is
      controlled by periplasmic lipoproteins that anchor the outer membrane to the
      periplasmic peptidoglycan polymer. This periplasm intermembrane distance is
      critical for sensing outer membrane damage and dictates length of the flagellar
      periplasmic rotor, which controls motility. These exciting results resolve
      longstanding debates about whether the periplasmic distance has a biological
      function and raise the possibility that the mechanisms for maintenance of
      periplasmic size could be exploited for antibiotic development.

PMID- 29342146
TI  - A theory of how active behavior stabilises neural activity: Neural gain
      modulation by closed-loop environmental feedback.
AB  - During active behaviours like running, swimming, whisking or sniffing, motor
      actions shape sensory input and sensory percepts guide future motor commands.
      Ongoing cycles of sensory and motor processing constitute a closed-loop feedback
      system which is central to motor control and, it has been argued, for perceptual
      processes. This closed-loop feedback is mediated by brainwide neural circuits but
      how the presence of feedback signals impacts on the dynamics and function of
      neurons is not well understood. Here we present a simple theory suggesting that
      closed-loop feedback between the brain/body/environment can modulate neural gain
      and, consequently, change endogenous neural fluctuations and responses to sensory
      input. We support this theory with modeling and data analysis in two vertebrate
      systems. First, in a model of rodent whisking we show that negative feedback
      mediated by whisking vibrissa can suppress coherent neural fluctuations and
      neural responses to sensory input in the barrel cortex. We argue this suppression
      provides an appealing account of a brain state transition (a marked change in
      global brain activity) coincident with the onset of whisking in rodents.
      Moreover, this mechanism suggests a novel signal detection mechanism that
      selectively accentuates active, rather than passive, whisker touch signals. This
      mechanism is consistent with a predictive coding strategy that is sensitive to
      the consequences of motor actions rather than the difference between the
      predicted and actual sensory input. We further support the theory by re-analysing
      previously published two-photon data recorded in zebrafish larvae performing
      closed-loop optomotor behaviour in a virtual swim simulator. We show, as
      predicted by this theory, that the degree to which each cell contributes in
      linking sensory and motor signals well explains how much its neural fluctuations
      are suppressed by closed-loop optomotor behaviour. More generally we argue that
      our results demonstrate the dependence of neural fluctuations, across the brain,
      on closed-loop brain/body/environment interactions strongly supporting the idea
      that brain function cannot be fully understood through open-loop approaches
      alone.

PMID- 29342147
TI  - Missed opportunities: Do states require screening of children for health
      conditions that interfere with learning?
AB  - METHODS: Investigators reviewed websites of state departments of health and
      education, and legislation for all 50 states and DC. For states with mandated
      screenings and a required form, investigators applied structured analysis to
      assess HBL inclusion. RESULTS: No state mandated that schools require screening
      for all 7 HBLs. Less than half (49%) required comprehensive school health
      examinations and only 12 states plus DC required a specific form. Of these, 12 of
      the forms required documentation of vision screening, 11 of hearing screening,
      and 12 of dental screening. Ten forms asked about asthma and 9 required
      documentation of lead testing. Seven asked about general well-being, emotional
      problems, or mental health. None addressed hunger. When including states without
      comprehensive school health examination requirements, the most commonly required
      HBL screenings were for vision (80% of states; includes DC), hearing (75% of
      states; includes DC) and dental (24% of state; includes DC). CONCLUSION: The lack
      of state mandated requirements for regular student health screening represents a
      missed opportunity to identify children with HBLs. Without state mandates,
      accompanying comprehensive forms, and protocols, children continue to be at risk
      of untreated health conditions that can undermine their success in school.

PMID- 29342148
TI  - A strong summer phytoplankton bloom southeast of Vietnam in 2007, a transitional
      year from El Nino to La Nina.
AB  - Summer upwelling occurs frequently off the southeast Vietnam coast in the western
      South China Sea (SCS), where summer phytoplankton blooms generally appear during
      June-August. In this study, we investigate inter-annual variation of Ekman
      pumping and offshore transport, and its modulation on summer blooms southeast of
      Vietnam. The results indicate that there are low intensities of summer blooms in
      El Nino years, under higher sea surface temperatures (SST) and weaker winds.
      However, a different pattern of monthly chlorophyll a (Chl-a) blooms occurred in
      summer of 2007, a transitional stage from El Nino to La Nina, with weak (strong)
      wind and high (low) SST before (after) early July. There is a weak phytoplankton
      bloom before July 2007 and a strong phytoplankton bloom after July 2007. The
      abrupt change in the wind intensity may enhance the upwelling associated with
      Ekman pumping and offshore Ekman transport, bringing more high-nutrient water
      into the upper layer from the subsurface, and thus leading to an evident Chl-a
      bloom in the region.

PMID- 29342149
TI  - Low expression of IL-18 and IL-18 receptor in human skeletal muscle is associated
      with systemic and intramuscular lipid metabolism-Role of HIV lipodystrophy.
AB  - INTRODUCTION: Interleukin (IL)-18 is involved in regulation of lipid and glucose
      metabolism. Mice lacking whole-body IL-18 signalling are prone to develop weight
      gain and insulin resistance, a phenotype which is associated with impaired fat
      oxidation and ectopic skeletal muscle lipid deposition. IL-18 mRNA is expressed
      in human skeletal muscle but a role for IL-18 in muscle has not been identified.
      Patients with HIV-infection and lipodystrophy (LD) are characterized by lipid and
      glucose disturbances and increased levels of circulating IL-18. We hypothesized
      that skeletal muscle IL-18 and IL-18 receptor (R) expression would be altered in
      patients with HIV-lipodystrophy. DESIGN AND METHODS: Twenty-three HIV-infected
      patients with LD and 15 age-matched healthy controls were included in a cross
      sectional study. Biopsies from the vastus lateralis muscle were obtained and IL
      18 and IL-18R mRNA expression were measured by real-time PCR and sphingolipids
      (ceramides, sphingosine, sphingosine-1-Phosphate, sphinganine) were measured by
      HPLC. Insulin resistance was assessed by HOMA and the insulin response during an
      OGTT. RESULTS: Patients with HIV-LD had a 60% and 54% lower level of muscular IL
      18 and IL-18R mRNA expression, respectively, compared to age-matched healthy
      controls. Patients with HIV-LD had a trend towards increased levels of ceramide
      (18.3+/-4.7 versus 14.8+/-3.0,p = 0.06) and sphingosine (0.41+/-0.13 versus
      0.32+/-0.07, and lower level of sphinganine (p = 0.06). Low levels of muscle IL
      18 mRNA correlated to high levels of ceramides (r = -0.31, p = 0.038) and
      sphingosine-1P (r = -0.29, p = 0.046) in skeletal muscle, whereas such a
      correlation was not found in healthy controls. Low expression of IL-18 mRNA in
      skeletal muscle correlated to elevated concentration of circulating triglycerides
      (Rp = -0.73, p<0.0001). Neither muscle expression of IL-18 mRNA or ceramide
      correlated to parameters of insulin resistance. CONCLUSION: IL-18 (mRNA) in
      skeletal muscle appears to be involved in the regulation of intramuscular lipid
      metabolism and hypertriglyceridemia.

PMID- 29342150
TI  - In vivo osteoconductivity of surface modified Ti-29Nb-13Ta-4.6Zr alloy with low
      dissolution of toxic trace elements.
AB  - Simulated Body Fluid (SBF) has served as a useful standard to check the
      bioactivity of implant materials for years. However, it is not perfectly able to
      imitate human serum; sometimes disparities between the SBF test and animal test
      were confirmed. Therefore, to ensure the reliability of the results of the SBF
      test obtained from our previous study, an animal study was performed to check
      osteoconductivity of surface modified implant materials. Three types of solution
      processes, hydrothermal (H), electrochemical (E), and hydrothermal
      electrochemical (HE), were performed on the Ti-29Nb-13Ta-4.6Zr alloy (TNTZ) to
      improve its bioactivity, and their bioactivities were measured in vivo using bone
      implant contacts (BICs). BICs of the HE- and H-treated samples were significantly
      higher than that of the control. Metal ion diffusion towards the bone was also
      evaluated to examine the adverse effect of metal ions. No metal ion diffusion was
      observed, indicating the safety of our solution processed implant materials.

PMID- 29342151
TI  - CD8 signaling in microglia/macrophage M1 polarization in a rat model of cerebral
      ischemia.
AB  - Classical or M1 activity of microglia/macrophages has been described in several
      neurodegenerative and brain inflammatory conditions and has also been linked to
      expansion of ischemic injury in post-stroke brain. While different pathways of M1
      polarization have been suggested to occur in the post-stroke brain, the precise
      underlying mechanisms remain undefined. Using a transient middle cerebral artery
      occlusion (MCAO) rat model, we showed a progressive M2 to M1 polarization in the
      perilesional brain region with M1 cells becoming one of the dominant subsets by
      day 4 post-stroke. Comparing key receptors involved in M1 polarization (CD8,
      IFNgammaR, Clec4, FcgammaR, TLR3 and TLR4) and their signal transducers (Syk,
      Stat1, Irf3, and Traf6) at the day 4 time point, we showed a strong upregulation
      of CD8 along with SYK transducer in dissected perilesional brain tissue. We
      further showed that CD8 expression in the post-stroke brain was associated with
      activated (CD68+) macrophages and that progressive accumulation of CD8+CD68+
      cells in the post-stroke brain coincided with increased iNOS (M1 marker) and
      reduced Arg1 (M2 marker) expression on these cells. In vitro ligand-based
      stimulation of the CD8 receptor caused increased iNOS expression and an enhanced
      capacity to phagocytose E. coli particles; and interestingly, CD8 stimulation was
      also able to repolarize IL4-treated M2 cells to an M1 phenotype. Our data suggest
      that increased CD8 signaling in the post-stroke brain is primarily associated
      with microglia/macrophages and can independently drive M1 polarization, and that
      modulation of CD8 signaling could be a potential target to limit secondary post
      stroke brain damage.

PMID- 29342152
TI  - Do nursery habitats provide shelter from flow for juvenile fish?
AB  - Juvenile fish nurseries are an essential life stage requirement for the
      maintenance of many fish populations. With many inshore habitats globally in
      decline, optimising habitat management by increasing our understanding of the
      relationship between juvenile fish and nursery habitats may be a prudent
      approach. Previous research on post-settlement snapper (Chrysophrys auratus) has
      suggested that structure may provide a water flow refuge, allowing snapper to
      access high water flow sites that will also have a high flux of their pelagic
      prey. We investigated this hypothesis by describing how Artificial Seagrass Units
      (ASUs) modified water flow while also using a multi-camera set up to quantify
      snapper position in relation to this water flow environment. Horizontal water
      flow was reduced on the down-current side of ASUs, but only at the height of the
      seagrass canopy. While the highest abundance of snapper did occur down-current of
      the ASUs, many snapper also occupied other locations or were too high in the
      water column to receive any refuge from water flow. The proportion of snapper
      within the water column was potentially driven by strategy to access zooplankton
      prey, being higher on the up-current side of ASUs and on flood tides. It is
      possible that post-settlement snapper alternate position to provide opportunities
      for both feeding and flow refuging. An alternative explanation relates to an
      observed interaction between post-settlement snapper and a predator, which
      demonstrated that snapper can utilise habitat structure when threatened. The
      nature of this relationship, and its overall importance in determining the value
      of nursery habitats to post-settlement snapper remains an elusive next step.

PMID- 29342153
TI  - The impact of optic nerve and related characteristics on disc area measurements
      derived from different imaging techniques.
AB  - PURPOSE: Optic nerve head (ONH) assessment and its interpretation in healthy
      patients and those with glaucoma remains a pivotal topic specifically considering
      rapid advancements in imaging technologies. We undertook a large-scale, mixed
      cohort, comparative study to assess the correlation of optic disc measurements
      between different imaging modalities and investigated the impact of patient and
      disc associated parameters. METHODS: ONH sizes were obtained from one randomly
      selected eye of each of 209 patients using stereophotography, confocal scanning
      laser ophthalmoscopy and two different optical coherence tomographers (OCT).
      Patient related data, glaucoma status and optic disc variables, specifically
      oblique insertion, torsion, presence of beta PPA and spherical equivalent were
      recorded. Measurements between imaging modalities were analysed using Pearson
      correlation, linear regression analysis and Blend-Altman plots. Individual
      variables were compared applying multivariate regression analysis, ANOVA and chi
      square statistics was used to determine correlations between patient and clinical
      characteristics. RESULTS: Absolute measurements significantly differed between
      imaging modalities generally producing smaller measurements for OCT derived
      measurements of Bruch's membrane opening (BMO). Pairwise correlations between
      imaging modalities were between 0.83 and 0.93 for discs without myopia, oblique
      insertion, or beta PPA. These features impacted on measurements for individual
      modalities and consequently contributed to inconsistencies and variability.
      CONCLUSION: In comparison to planimetry, OCT derived BMO measurements are more
      variable in the presence of oblique insertion, beta PPA or magnification errors
      due to myopia. Impact of these factors, however, differs between instruments and
      needs to be considered to accurately interpret optic disc features in particular
      within the context of glaucoma diagnosis.

PMID- 29342154
TI  - Three unrelated and unexpected amino acids determine the susceptibility of the
      interface cysteine to a sulfhydryl reagent in the triosephosphate isomerases of
      two trypanosomes.
AB  - Proteins with great sequence similarity usually have similar structure, function
      and other physicochemical properties. But in many cases, one or more of the
      physicochemical or functional characteristics differ, sometimes very
      considerably, among these homologous proteins. To better understand how critical
      amino acids determine quantitative properties of function in proteins, the
      responsible residues must be located and identified. This can be difficult to
      achieve, particularly in cases where multiple amino acids are involved. In this
      work, two triosephosphate isomerases with very high similarity from two related
      human parasites were used to address one such problem. We demonstrate that a
      seventy-fold difference in the reactivity of an interface cysteine to the
      sulfhydryl reagent methylmethane sulfonate in these two enzymes depends on three
      amino acids located far away from this critical residue and which could not have
      been predicted using other current methods. Starting from previous observations
      with chimeric proteins involving these two triosephosphate isomerases, we
      developed a strategy involving additive mutant enzymes and selected site directed
      mutants to locate and identify the three amino acids. These three residues seem
      to induce changes in the interface cysteine in reactivity by increasing (or
      decreasing) its apparent pKa. Some enzymes with four to seven mutations also
      exhibited altered reactivity. This study completes a strategy for identifying key
      residues in the sequences of proteins that can have applications in future
      protein structure-function studies.

PMID- 29342155
TI  - Nanoscopic X-ray fluorescence imaging and quantification of intracellular key
      elements in cryofrozen Friedreich's ataxia fibroblasts.
AB  - Synchrotron radiation based nanoscopic X-ray fluorescence (SR nano-XRF) analysis
      can visualize trace level elemental distribution in a fully quantitative manner
      within single cells. However, in-air XRF analysis requires chemical fixation
      modifying the cell's chemical composition. Here, we describe first nanoscopic XRF
      analysis upon cryogenically frozen (-150 degrees C) fibroblasts at the ID16A-NI
      'Nano-imaging' end-station located at the European Synchrotron Radiation Facility
      (ESRF) in Grenoble (France). Fibroblast cells were obtained from skin biopsies
      from control and Friedreich's ataxia (FRDA) patients. FRDA is an autosomal
      recessive disorder with dysregulation of iron metabolism as a key feature. By
      means of the X-ray Fundamental Parameter (FP) method, including absorption
      correction of the ice layer deposited onto the fibroblasts, background-corrected
      mass fraction elemental maps of P, S, Cl, K, Ca, Fe and Zn of entire cryofrozen
      human fibroblasts were obtained. Despite the presence of diffracting
      microcrystals in the vitreous ice matrix and minor sample radiation damage
      effects, clusters of iron-rich hot-spots with similar mass fractions were found
      in the cytoplasm of both control and FRDA fibroblasts. Interestingly, no
      significant difference in the mean iron concentration was found in the cytoplasm
      of FRDA fibroblasts, but a significant decrease in zinc concentration. This
      finding might underscore metal dysregulation, beyond iron, in cells derived from
      FRDA patients. In conclusion, although currently having slightly increased limits
      of detection (LODs) compared to non-cryogenic mode, SR based nanoscopic XRF under
      cryogenic sample conditions largely obliterates the debate on chemical sample
      preservation and provides a unique tool for trace level elemental imaging in
      single cells close to their native state with a superior spatial resolution of 20
      nm.

PMID- 29342156
TI  - Specialized attachment structure of the fish pathogenic oomycete Saprolegnia
      parasitica.
AB  - The secondary cysts of the fish pathogen oomycete Saprolegnia parasitica possess
      bundles of long hooked hairs that are characteristic to this economically
      important pathogenic species. Few studies have been carried out on elucidating
      their specific role in the S. parasitica life cycle and the role they may have in
      the infection process. We show here their function by employing several
      strategies that focus on descriptive, developmental and predictive approaches.
      The strength of attachment of the secondary cysts of this pathogen was compared
      to other closely related species where bundles of long hooked hairs are absent.
      We found that the attachment of the S. parasitica cysts was around three times
      stronger than that of other species. The time sequence and influence of selected
      factors on morphology and the number of the bundles of long hooked hairs
      conducted by scanning electron microscopy study revealed that these are dynamic
      structures. They are deployed early after encystment, i.e., within 30 sec of
      zoospore encystment, and the length, but not the number, of the bundles steadily
      increased over the encystment period. We also observed that the number and length
      of the bundles was influenced by the type of substrate and encystment treatment
      applied, suggesting that these structures can adapt to different substrates
      (glass or fish scales) and can be modulated by different signals (i.e., protein
      media, 50 mM CaCl2 concentrations, carbon particles). Immunolocalization studies
      evidenced the presence of an adhesive extracellular matrix. The bioinformatic
      analyses of the S. parasitica secreted proteins showed that there is a high
      expression of genes encoding domains of putative proteins related to the
      attachment process and cell adhesion (fibronectin and thrombospondin) coinciding
      with the deployment stage of the bundles of long hooked hairs formation. This
      suggests that the bundles are structures that might contribute to the adhesion of
      the cysts to the host because they are composed of these adhesive proteins and/or
      by increasing the surface of attachment of this extracellular matrix.

PMID- 29342157
TI  - Timing of maternal death: Levels, trends, and ecological correlates using sibling
      data from 34 sub-Saharan African countries.
AB  - Millennium Development Goal 5 has not been universally achieved, particularly in
      sub-Saharan Africa. Understanding whether maternal deaths occur during pregnancy,
      childbirth, or puerperium is important to effectively plan maternal health
      programs and allocate resources. Our main research objectives are to (1) describe
      the proportions and rates of mortality for the antepartum, intrapartum, and
      postpartum periods; (2) document how these trends vary by sub-region; and (3)
      investigate ecological correlations between these rates and maternal care
      interventions. We used data from the Demographic and Health Survey program, which
      comprises 84 surveys from 34 sub-Saharan African countries conducted between 1990
      and 2014. We calculated age-standardized maternal mortality rates and time
      specific maternal mortality rates and proportions, and we assessed correlations
      with maternal care coverage. We found high levels of maternal mortality in all
      three periods. Time-specific maternal mortality rates varied by country and
      region, with some showing an orderly decline in all three periods and others
      exhibiting alarming increases in antepartum and postpartum mortality. Ecological
      analysis showed that antenatal care coverage was significantly associated with
      low antepartum mortality, whereas the presence of a skilled attendant at
      childbirth was significantly associated with low postpartum mortality. In sub
      Saharan Africa, maternal deaths occur at high rates in all three risk periods,
      and vary substantially by country and region. The provision of maternal care is a
      predictor of time-specific maternal mortality. These results confirm the need for
      country-specific interventions during the continuum of care to achieve the global
      commitment to eliminating preventable maternal mortality.

PMID- 29342158
TI  - Real-time community detection in full social networks on a laptop.
AB  - For a broad range of research and practical applications it is important to
      understand the allegiances, communities and structure of key players in society.
      One promising direction towards extracting this information is to exploit the
      rich relational data in digital social networks (the social graph). As global
      social networks (e.g., Facebook and Twitter) are very large, most approaches make
      use of distributed computing systems for this purpose. Distributing graph
      processing requires solving many difficult engineering problems, which has lead
      some researchers to look at single-machine solutions that are faster and easier
      to maintain. In this article, we present an approach for analyzing full social
      networks on a standard laptop, allowing for interactive exploration of the
      communities in the locality of a set of user specified query vertices. The key
      idea is that the aggregate actions of large numbers of users can be compressed
      into a data structure that encapsulates the edge weights between vertices in a
      derived graph. Local communities can be constructed by selecting vertices that
      are connected to the query vertices with high edge weights in the derived graph.
      This compression is robust to noise and allows for interactive queries of local
      communities in real-time, which we define to be less than the average human
      reaction time of 0.25s. We achieve single-machine real-time performance by
      compressing the neighborhood of each vertex using minhash signatures and
      facilitate rapid queries through Locality Sensitive Hashing. These techniques
      reduce query times from hours using industrial desktop machines operating on the
      full graph to milliseconds on standard laptops. Our method allows exploration of
      strongly associated regions (i.e., communities) of large graphs in real-time on a
      laptop. It has been deployed in software that is actively used by social network
      analysts and offers another channel for media owners to monetize their data,
      helping them to continue to provide free services that are valued by billions of
      people globally.

PMID- 29342159
TI  - Prediction of novel target genes and pathways involved in bevacizumab-resistant
      colorectal cancer.
AB  - Bevacizumab combined with cytotoxic chemotherapy is the backbone of metastatic
      colorectal cancer (mCRC) therapy; however, its treatment efficacy is hampered by
      therapeutic resistance. Therefore, understanding the mechanisms underlying
      bevacizumab resistance is crucial to increasing the therapeutic efficacy of
      bevacizumab. The Gene Expression Omnibus (GEO) database (dataset, GSE86525) was
      used to identify the key genes and pathways involved in bevacizumab-resistant
      mCRC. The GEO2R web tool was used to identify differentially expressed genes
      (DEGs). Functional and pathway enrichment analyses of the DEGs were performed
      using the Database for Annotation, Visualization, and Integrated
      Discovery(DAVID). Protein-protein interaction (PPI) networks were established
      using the Search Tool for the Retrieval of Interacting Genes/Proteins
      database(STRING) and visualized using Cytoscape software. A total of 124 DEGs
      were obtained, 57 of which upregulated and 67 were downregulated. PPI network
      analysis showed that seven upregulated genes and nine downregulated genes
      exhibited high PPI degrees. In the functional enrichment, the DEGs were mainly
      enriched in negative regulation of phosphate metabolic process and positive
      regulation of cell cycle process gene ontologies (GOs); the enriched pathways
      were the phosphoinositide 3-kinase-serine/threonine kinase signaling pathway,
      bladder cancer, and microRNAs in cancer. Cyclin-dependent kinase inhibitor
      1A(CDKN1A), toll-like receptor 4 (TLR4), CD19 molecule (CD19), breast cancer 1,
      early onset (BRCA1), platelet-derived growth factor subunit A (PDGFA), and matrix
      metallopeptidase 1 (MMP1) were the DEGs involved in the pathways and the PPIs.
      The clinical validation of the DEGs in mCRC (TNM clinical stages 3 and 4)
      revealed that high PDGFA expression levels were associated with poor overall
      survival, whereas high BRCA1 and MMP1 expression levels were associated with
      favorable progress free survival(PFS). The identified genes and pathways can be
      potential targets and predictors of therapeutic resistance and prognosis in
      bevacizumab-treated patients with mCRC.

PMID- 29342160
TI  - Expression of the lux genes in Streptococcus pneumoniae modulates pilus
      expression and virulence.
AB  - Bioluminescence has been harnessed for use in bacterial reporter systems and for
      in vivo imaging of infection in animal models. Strain Xen35, a bioluminescent
      derivative of Streptococcus pneumoniae serotype 4 strain TIGR4 was previously
      constructed for use for in vivo imaging of infections in animal models. We have
      shown that strain Xen35 is less virulent than its parent TIGR4 and that this is
      associated with the expression of the genes for bioluminescence. The expression
      of the luxA-E genes in the pneumococcus reduces virulence and down regulates the
      expression of the pneumococcal pilus.

PMID- 29342161
TI  - Association between circulating levels of sex steroid hormones and esophageal
      adenocarcinoma in the FINBAR Study.
AB  - BACKGROUND: Esophageal adenocarcinoma (EA) is characterized by a strong male
      predominance. Sex steroid hormones have been hypothesized to underlie this sex
      disparity, but no population-based study to date has examined this potential
      association. METHODS: Using mass spectrometry and ELISA, we quantitated sex
      steroid hormones and sex hormone binding globulin, respectively, in plasma from
      males- 172 EA cases and 185 controls-within the Factors Influencing the
      Barrett/Adenocarcinoma Relationship (FINBAR) Study, a case-control investigation
      conducted in Northern Ireland and Ireland. Multivariable adjusted logistic
      regression was used to calculate odds ratios (ORs) and 95% confidence intervals
      (CIs) for associations between circulating hormones and EA. RESULTS: Higher
      androgen:estrogen ratio metrics were associated with increased odds of EA (e.g.,
      testosterone:estradiol ratio ORQ4 v. Q1 = 2.58, 95%CI = 1.23-5.43; Ptrend =
      0.009). All estrogens and androgens were associated with significant decreased
      odds of EA. When restricted to individuals with minimal to no decrease in body
      mass index, the size of association for the androgen:estrogen ratio was not
      greatly altered. CONCLUSIONS: This first study of sex steroid hormones and EA
      provides tentative evidence that androgen:estrogen balance may be a factor
      related to EA. Replication of these findings in prospective studies is needed to
      enhance confidence in the causality of this effect.

PMID- 29342162
TI  - Comparison of diagnostic methods to detect Histoplasma capsulatum in serum and
      blood samples from AIDS patients.
AB  - BACKGROUND: Although early and rapid detection of histoplasmosis is essential to
      prevent morbidity and mortality, few diagnostic tools are available in resource
      limited areas, especially where it is endemic and HIV/AIDS is also epidemic.
      Thus, we compared conventional and molecular methods to detect Histoplasma
      capsulatum in sera and blood from HIV/AIDS patients. METHODOLOGY: We collected a
      total of 40 samples from control volunteers and patients suspected of
      histoplasmosis, some of whom were also infected with other pathogens. Samples
      were then analyzed by mycological, serological, and molecular methods, and
      stratified as histoplasmostic with (group I) or without AIDS (group II),
      uninfected (group III), and infected with HIV and other pathogens only (group
      IV). All patients were receiving treatment for histoplasmosis and other
      infections at the time of sample collection. RESULTS: Comparison of conventional
      methods with nested PCR using primers against H. capsulatum 18S rRNA (HC18S),
      5.8S rRNA ITS (HC5.8S-ITS), and a 100 kDa protein (HC100) revealed that
      sensitivity against sera was highest for PCR with HC5.8S-ITS, followed by
      immunoblotting, double immunodiffusion, PCR with HC18S, and PCR with HC100.
      Specificity was equally high for double immunodiffusion, immunoblotting and PCR
      with HC100, followed for PCR with HC18S and HC5.8-ITS. Against blood, sensitivity
      was highest for PCR with HC5.8S-ITS, followed by PCR with HC18S, Giemsa staining,
      and PCR with HC100. Specificity was highest for Giemsa staining and PCR with
      HC100, followed by PCR with HC18S and HC5.8S-ITS. PCR was less efficient in
      patients with immunodeficiency due to HIV/AIDS and/or related diseases.
      CONCLUSION: Molecular techniques may detect histoplasmosis even in cases with
      negative serology and mycology, potentially enabling early diagnosis.

PMID- 29342163
TI  - Doxylamine-pyridoxine for nausea and vomiting of pregnancy randomized placebo
      controlled trial: Prespecified analyses and reanalysis.
AB  - BACKGROUND: Doxylamine-pyridoxine is recommended as a first line treatment for
      nausea and vomiting during pregnancy and it is commonly prescribed. We re
      analysed the findings of a previously reported superiority trial of doxylamine
      pyridoxine for the treatment of nausea and vomiting during pregnancy using the
      clinical study report obtained from Health Canada. METHODS AND FINDINGS: We re
      analysed individual level data for a parallel arm randomized controlled trial
      that was conducted in six outpatient obstetrical practices in the United States.
      Pregnant women between 7 and 14 weeks of gestation with moderate nausea and
      vomiting of pregnancy symptoms. The active treatment was a tablet containing both
      doxylamine 10 mg and pyridoxine 10 mg taken between 2 and 4 times per day for 14
      days depending on symptoms. The control was an identical placebo tablet taken
      using the same instructions. The primary outcome measure was improvement in
      nausea and vomiting of symptoms scores using the 13-point pregnancy unique
      quantification of emesis scale between baseline and 14 days using an ANCOVA. 140
      participants were randomized into each group. Data for 131 active treatment
      participants and 125 control participants were analysed. On the final day of the
      trial, 101 active treatment participants and 86 control participants provided
      primary outcome measures. There was greater improvement in symptoms scores with
      doxylamine-pyridoxine compared with placebo (0.73 points; 95% CI 0.21 to 1.25)
      when last observation carried forward imputation was used for missing data but
      the difference is not statistically significant using other approaches to missing
      data (e.g. 0.38; 95% CI -0.08 to 0.84 using complete data). CONCLUSIONS: There is
      a trend towards efficacy for nausea and vomiting symptoms with doxylamine
      pyridoxine compared with placebo but the statistical significance of the
      difference depends on the method of handling missing data and the magnitude of
      the difference suggests that there is no clinically important benefit employing
      the prespecified minimal clinically important difference or "expected difference"
      of 3 points. TRIAL REGISTRATION: Clinical Trial NCT00614445.

PMID- 29342164
TI  - Environmental dust inhalation in the European badger (Meles meles): Systemic
      distribution of silica-laden macrophages, pathological changes, and association
      with Mycobacterium bovis infection status.
AB  - Chronic inhalation of crystalline silica and silicates may lead to severe lung
      disease in humans, termed silicosis. The disease is an occupational health
      concern in miners and related professions worldwide. Silicosis is also a strong
      risk factor for tuberculosis in humans. Due to its subterranean lifestyle, the
      European badger (Meles meles) is continuously exposed to environmental dust,
      while this species is also susceptible to tuberculosis, caused by Mycobacterium
      bovis. To date, a thorough investigation of mineral dust retention and its
      possible implication as a risk factor for mycobacterial infection in badgers has
      not been performed. The aims of this retrospective histological study were (1) to
      describe the systemic tissue distribution of silica-laden macrophages (SLMs) in
      badgers; (2) to compare the amount of SLMs in tissues of badgers of differing M.
      bovis infection status, pulmonary SLM burden and age; and (3) to assess whether
      inflammation was associated with SLMs. We assessed lung, lymph nodes, liver and
      spleen of 60 wild-caught badgers of known M. bovis infection status for the
      presence of SLMs using polarizing light microscopy. SLMs were consistently
      present within the lungs and were widely distributed throughout the lymphatic
      system. No inflammatory reaction to SLMs, as occurs in human silicosis, was
      observed in any tissue. Distribution and amount of SLMs were similar between M.
      bovis positive and negative badgers, and we were not able to show an association
      between the amount of SLMs and M. bovis infection status. The amount of SLMs
      within intra- and extrathoracic lymph nodes was positively associated with the
      amount of pulmonary SLMs, and with age. This is the first report of substantial
      and systemic tissue retention of mineral dust particles in a mammalian species
      lacking associated chronic inflammation (i.e. silicosis). We further highlight
      different pathogenetic mechanisms underlying silicosis and benign SLM
      accumulations following siliceous dust inhalation.

PMID- 29342165
TI  - Increased colon cancer risk after severe Salmonella infection.
AB  - BACKGROUND: Colon cancer constitutes one of the most frequent malignancies.
      Previous studies showed that Salmonella manipulates host cell signaling pathways
      and that Salmonella Typhimurium infection facilitates colon cancer development in
      genetically predisposed mice. This epidemiological study examined whether severe
      Salmonella infection, usually acquired from contaminated food, is associated with
      increased colon cancer risk in humans. METHODS AND FINDINGS: We performed a
      nationwide registry-based study to assess colon cancer risk after diagnosed
      Salmonella infection. National infectious disease surveillance records (1999
      2015) for Dutch residents aged >=20 years when diagnosed with salmonellosis (n =
      14,264) were linked to the Netherlands Cancer Registry. Salmonella-infected
      patients were laboratory-confirmed under medical consultation after 1-2 weeks of
      illness. These datasets also contained information on Salmonella serovar and type
      of infection. Colon cancer risk (overall and per colon subsite) among patients
      with a diagnosed Salmonella infection was compared with expected colon cancer
      risk in the general population. Data from the nationwide registry of histo- and
      cytopathology (PALGA) and Statistics Netherlands (CBS) allowed assessing
      potential effects of age, gender, latency, socioeconomic status, genetic
      predisposition, inflammatory bowel disease (IBD), and tumor features. We found
      that compared to the general population, colon cancer risk was significantly
      increased (standardized incidence ratio [SIR] 1.54; 95%CI 1.09-2.10) among
      patients with Salmonella infection diagnosed <60 years of age. Such increased
      risk concerned specifically the ascending/transverse colon (SIR 2.12; 95%CI 1.38
      3.09) after S. Enteritidis infection (SIR 2.97; 95%CI 1.73-4.76). Salmonellosis
      occurred more frequently among colon cancer patients with pre-infectious IBD, a
      known risk factor for colon cancer. Colon tumors of patients with a history of
      Salmonella infection were mostly of low grade. CONCLUSIONS: Patients diagnosed
      with severe salmonellosis have an increased risk of developing cancer in the
      ascending/transverse parts of the colon. This risk concerns particularly S.
      Enteritidis infection, suggesting a contribution of this major foodborne pathogen
      to colon cancer development.

PMID- 29342166
TI  - Effects of vitamin D on insulin resistance and myosteatosis in diet-induced obese
      mice.
AB  - Epidemiological studies pointed out to a strong association between vitamin D
      deficiency and type 2 diabetes prevalence. However, the role of vitamin D
      supplementation in the skeletal muscle, a tissue that play a crucial role in the
      maintenance of glucose homeostasis, has been scarcely investigated so far. On
      this basis, this study aimed to evaluate the effect of vitamin D supplementation
      in a murine model of diet-induced insulin resistance with particular attention to
      the effects evoked on the skeletal muscle. Male C57BL/6J mice (n = 40) were fed
      with a control or a High Fat-High Sugar (HFHS) diet for 4 months. Subsets of
      animals were treated for 2 months with vitamin D (7 MUg.kg-1, i.p. three
      times/week). HFHS diet induced body weight increase, hyperglycemia and impaired
      glucose tolerance. HFHS animals showed an impaired insulin signaling and a marked
      fat accumulation in the skeletal muscle. Vitamin D reduced body weight and
      improved systemic glucose tolerance. In addition, vitamin D restored the impaired
      muscle insulin signaling and reverted myosteatosis evoked by the diet. These
      effects were associated to decreased activation of NF-kappaB and lower levels of
      TNF-alpha. Consistently, a significantly decreased activation of the SCAP/SREBP
      lipogenic pathway and lower levels of CML protein adducts and RAGE expression
      were observed in skeletal muscle of animals treated with vitamin D. Collectively,
      these data indicate that vitamin D-induced selective inhibition of signaling
      pathways (including NF-kappaB, SCAP/SREBP and CML/RAGE cascades) within the
      skeletal muscle significantly contributed to the beneficial effects of vitamin D
      supplementation against diet-induced metabolic derangements.

PMID- 29342167
TI  - Effects of ammonium-based ionic liquids and 2,4-dichlorophenol on the
      phospholipid fatty acid composition of zebrafish embryos.
AB  - Ionic liquids consisting of a combination of herbicidal anions with a quaternary
      ammonium cation act as efficient herbicides, which are under consideration to be
      used in the agriculture. In the present study, we used embryos of the zebrafish
      (Danio rerio) as a model to assess the toxic potential of ammonium-based ionic
      liquids for aquatic organisms. As we assumed interference of the partially
      hydrophobic ionic liquid cation with lipids, we investigated the adaptation
      response in the lipid composition of the zebrafish embryos, triggered by the
      ionic compound. Therefore, the impact of ammonium-based ionic liquids with
      different lengths of the alkyl chain ([C6,C6,C1,C1N][Br], [C8,C8,C1,C1N][Br]) on
      the phospholipid fatty acid (PLFA) profile of zebrafish embryos up to 72 hours
      post fertilization (hpf) was examined. Furthermore, the changes in the
      unsaturation index (UI) of PLFAs, as the sum parameter of membrane fluidity in
      eukaryotic cells, were presented. The PLFA's UI in the zebrafish embryos upon
      exposure to quaternary ammonium salts was compared to the UI of the embryos upon
      exposure to nonionic 2,4-dichlorophenol, which has a similar hydrophobicity but
      is structurally different to [C8,C8,C1,C1N][Br]. It was shown that for ammonium
      based ionic liquid precursors non-specific mode of action occurs and the toxic
      effect on lipid composition of zebrafish embryos can be well predicted based on
      chemical properties, like hydrophobicity. Furthermore, the changes in PLFAs,
      expressed by the UI, can be useful to study toxic effects of organic
      contamination. However, for zebrafish embryos, after ionic liquids and 2,4-DCP
      exposure, the changes were observed at high lethal concentrations, which caused
      the incidence of lethality of 30 and 50% of a group of test animals.

PMID- 29342168
TI  - Reduction in Musca domestica fecundity by dsRNA-mediated gene knockdown.
AB  - House flies (Musca domestica) are worldwide agricultural pests with estimated
      control costs at $375 million annually in the U.S. Non-target effects and
      widespread resistance challenge the efficacy of traditional chemical control.
      Double stranded RNA (dsRNA) has been suggested as a biopesticide for M. domestica
      but a phenotypic response due to the induction of the RNAi pathway has not been
      demonstrated in adults. In this study female house flies were injected with dsRNA
      targeting actin-5C or ribosomal protein (RP) transcripts RPL26 and RPS6. Ovaries
      showed highly reduced provisioning and clutch reductions of 94-99% in RP dsRNA
      treated flies but not in actin-5C or GFP treated flies. Gene expression levels
      were significantly and specifically reduced in dsRNA injected groups but remained
      unchanged in the control dsGFP treated group. Furthermore, injections with an
      Aedes aegypti conspecific dsRNA designed against RPS6 did not impact fecundity,
      demonstrating species specificity of the RNAi response. Analysis of M. domestica
      tissues following RPS6 dsRNA injection showed significant reduction of transcript
      levels in the head, thorax, and abdomen but increased expression in ovarian
      tissues. This study demonstrates that exogenous dsRNA is specifically effective
      and has potential efficacy as a highly specific biocontrol intervention in adult
      house flies. Further work is required to develop effective methods for delivery
      of dsRNA to adult flies.

PMID- 29342169
TI  - Interactions between the invasive Burmese python, Python bivittatus Kuhl, and the
      local mosquito community in Florida, USA.
AB  - The Burmese python, Python bivittatus Kuhl, is a well-established invasive
      species in the greater Everglades ecosystem of southern Florida, USA. Most
      research on its ecological impacts focuses on its role as a predator and its
      trophic interactions with native vertebrate species, particularly mammals. Beyond
      predation, there is little known about the ecological interactions between P.
      bivittatus and native faunal communities. It is likely that established
      populations of P. bivittatus in southern Florida serve as hosts for native
      mosquito communities. To test this concept, we used mitochondrial cytochrome c
      oxidase subunit I DNA barcoding to determine the hosts of blood fed mosquitoes
      collected at a research facility in northern Florida where captive P. bivittatus
      and Argentine black and white tegu, Salvator merianae (Dumeril and Bibron), are
      maintained in outdoor enclosures, accessible to local mosquitoes. We recovered
      python DNA from the blood meals of three species of Culex mosquitoes: Culex
      erraticus (Dyar and Knab), Culex quinquefasciatus Say, and Culex pilosus (Dyar
      and Knab). Culex erraticus conclusively (P = 0.001; Fisher's Exact Test) took
      more blood meals from P. bivittatus than from any other available host. While the
      majority of mosquito blood meals in our sample were derived from P. bivittatus,
      only one was derived from S. merianae. These results demonstrate that local
      mosquitoes will feed on invasive P. bivittatus, a recently introduced host. If
      these interactions also occur in southern Florida, P. bivittatus may be involved
      in the transmission networks of mosquito-vectored pathogens. Our results also
      illustrate the potential of detecting the presence of P. bivittatus in the field
      through screening mosquito blood meals for their DNA.

PMID- 29342170
TI  - Determination of 2,4-Dichlorophenoxyacetic acid (2,4-D) in rat serum for
      pharmacokinetic studies with a simple HPLC method.
AB  - 2,4-Dichlorophenoxyacetic acid (2,4-D) is a chlorophenoxy herbicide used
      worldwide. We describe a high-performance liquid chromatography (HPLC) method
      with UV detection for the determination of 2,4-D in female and male rat serum.
      This allows to observe the change of serum 2,4-D concentration in rats with time
      and its pharmacokinetics characteristics with a simple, rapid, optimized and
      validated method. The serum samples are pretreated and introduced into the HPLC
      system. The analytes are separated in a XDB-C18 column with a mobile phase of
      acetonitrile (solvent A) and 0.02 M ammonium acetate (containing 0.1% formic
      acid) (solvent B) using a gradient elution at a flow rate of 1.0 mL/min. The
      wavelength for UV detection was set at 230 nm. Calibration curve for 2,4-D was
      constructed over a range of 0.1-400 mg/L. The method was successfully applied to
      study the pharmacokinetics of 2,4-D in rats in this study. After oral
      administration of 300 mg/kg and 60 mg/kg 2,4-D, the mean Cmax values were 601.9
      and 218.4 mg/L, the AUC0->infinity values were 23,722 and 4,127 mg*h/L and the
      clearance (Cl) were 1.10 and 0.02 L/(h*kg), respectively. The developed method
      was found to be specific, precise, reproducible and rapid.

PMID- 29342171
TI  - Health behavior associated with liver enzymes among obese Korean adolescents,
      2009-2014.
AB  - AIMS: Obesity is major risk factor for liver health. This study aimed to clarify
      whether specific health behaviors were associated with liver function in obese
      adolescents in Korea. METHODS: Based on national school health examination data
      from 2009 to 2014, 25,142 obese or overweight students were examined for
      aspartate transaminase and alanine transaminase levels, and health behaviors.
      Multiple logistic regression was used to calculate the odds ratio for liver
      enzyme elevation. RESULTS: Subjects who thought of themselves as "very fat" had a
      1.6 times higher odds ratio for liver enzyme elevations than those who thought of
      themselves as "normal." Those who consumed fast food 3 to 5 times weekly had 1.3
      times higher odds ratio (OR = 1.27, 95% confidence interval = 1.05-1.54) for the
      elevation of ALT than those who did not consume fast food. Those who took sugar
      sweetened beverage 3 to 5 times weekly had 1.2 times higher odds ratio (OR =
      1.24, 95% confidence interval = 1.07-1.42) for the elevation of ALT than those
      who did not take it. Those who played computer game more than 2 hours a day
      showed 1.1 times higher odds ratio (OR = 1.10, 95% confidence interval = 1.01
      1.21) for the elevation of ALT than those who did not. CONCLUSIONS: Specific food
      item and its frequency of consumption were identified for the positive and
      negative association with the elevation of liver enzymes. Self-image of body
      shape, sleeping time and need of help for alcohol or smoking problems also showed
      substantial association with the elevation.

PMID- 29342172
TI  - Driving factors of retention in care among HIV-positive MSM and transwomen in
      Indonesia: A cross-sectional study.
AB  - Little is known about the prevalence of and factors that influence retention in
      HIV-related care among Indonesian men who have sex with men (MSM) and transgender
      women (transwomen, or waria in Indonesian term). Therefore, we explored the
      driving factors of retention in care among HIV-positive MSM and waria in
      Indonesia. This cross-sectional study involved 298 self-reported HIV-positive MSM
      (n = 165) and waria (n = 133). Participants were recruited using targeted
      sampling and interviewed using a structured questionnaire. We applied a four-step
      model building process using multivariable logistic regression to examine how
      sociodemographic, predisposing, enabling, and reinforcing factors were associated
      with retention in care. Overall, 78.5% of participants were linked to HIV care
      within 3 months after diagnosis or earlier, and 66.4% were adequately retained in
      care (at least one health care visit every three months once a person is
      diagnosed with HIV). Being on antiretroviral therapy (adjusted odds ratio [AOR] =
      6.00; 95% confidence interval [CI]: 2.93-12.3), using the Internet to find HIV
      related information (AOR = 2.15; 95% CI: 1.00-4.59), and having medical insurance
      (AOR = 2.84; 95% CI: 1.27-6.34) were associated with adequate retention in care.
      Involvement with an HIV-related organization was associated negatively with
      retention in care (AOR = 0.47; 95% CI: 0.24-0.95). Future interventions should
      increase health insurance coverage and utilize the Internet to help MSM and waria
      to remain in HIV-related care, thereby assisting them in achieving viral
      suppression.

PMID- 29342173
TI  - Hormone induced differential transcriptome analysis of Sertoli cells during
      postnatal maturation of rat testes.
AB  - Sertoli cells (Sc) are unique somatic cells of testis that are the target of both
      FSH and testosterone (T) and regulate spermatogenesis. Although Sc of neonatal
      rat testes are exposed to high levels of FSH and T, robust differentiation of
      spermatogonial cells becomes conspicuous only after 11-days of postnatal age. We
      have demonstrated earlier that a developmental switch in terms of hormonal
      responsiveness occurs in rat Sc at around 12 days of postnatal age during the
      rapid transition of spermatogonia A to B. Therefore, such "functional maturation"
      of Sc, during pubertal development becomes prerequisite for the onset of
      spermatogenesis. However, a conspicuous difference in robust hormone (both T and
      FSH) induced gene expression during the different phases of Sc maturation
      restricts our understanding about molecular events necessary for the
      spermatogenic onset and maintenance. Here, using microarray technology, we for
      the first time have compared the differential transcriptional profile of Sc
      isolated and cultured from immature (5 days old), maturing (12 days old) and
      mature (60 days old) rat testes. Our data revealed that immature Sc express genes
      involved in cellular growth, metabolism, chemokines, cell division, MAPK and Wnt
      pathways, while mature Sc are more specialized expressing genes involved in
      glucose metabolism, phagocytosis, insulin signaling and cytoskeleton structuring.
      Taken together, this differential transcriptome data provide an important
      resource to reveal the molecular network of Sc maturation which is necessary to
      govern male germ cell differentiation, hence, will improve our current
      understanding of the etiology of some forms of idiopathic male infertility.

PMID- 29342174
TI  - Preference evaluation of ground beef by untrained subjects with three levels of
      finely textured beef.
AB  - After receiving bad publicity in 2012 and being removed from many ground beef
      products, finely textured beef (referred to as 'pink slime' by some) is making a
      comeback. Some of its proponents argue that consumers prefer ground beef
      containing finely textured beef, but no objective scientific party has tested
      this claim-that is the purpose of the present study. Over 200 untrained subjects
      participated in a sensory analysis in which they tasted one ground beef sample
      with no finely textured beef, another with 15% finely textured beef (by weight),
      and another with more than 15%. Beef with 15% finely textured beef has an
      improved juiciness (p < 0.01) and tenderness (p < 0.01) quality. However,
      subjects rate the flavor-liking and overall likeability the same regardless of
      the finely textured beef content. Moreover, when the three beef types are
      consumed as part of a slider (small hamburger), subjects are indifferent to the
      level of finely textured beef.

PMID- 29342176
TI  - The "handedness" of language: Directional symmetry breaking of sign usage in
      words.
AB  - Language, which allows complex ideas to be communicated through symbolic
      sequences, is a characteristic feature of our species and manifested in a
      multitude of forms. Using large written corpora for many different languages and
      scripts, we show that the occurrence probability distributions of signs at the
      left and right ends of words have a distinct heterogeneous nature. Characterizing
      this asymmetry using quantitative inequality measures, viz. information entropy
      and the Gini index, we show that the beginning of a word is less restrictive in
      sign usage than the end. This property is not simply attributable to the use of
      common affixes as it is seen even when only word roots are considered. We use the
      existence of this asymmetry to infer the direction of writing in undeciphered
      inscriptions that agrees with the archaeological evidence. Unlike traditional
      investigations of phonotactic constraints which focus on language-specific
      patterns, our study reveals a property valid across languages and writing
      systems. As both language and writing are unique aspects of our species, this
      universal signature may reflect an innate feature of the human cognitive
      phenomenon.

PMID- 29342175
TI  - Immunocontraceptive target repertoire defined by systematic identification of
      sperm membrane alloantigens in a single species.
AB  - Sperm competence in animal fertilization requires the collective activities of
      numerous sperm-specific proteins that are typically alloimmunogenic in females.
      Consequently, sperm membrane alloantigens are potential targets for
      contraceptives that act by blocking the proteins' functions in gamete
      interactions. Here we used a targeted proteomics approach to identify the major
      alloantigens in swine sperm membranes and lipid rafts, and thereby systematically
      defined the repertoire of these sperm-specific proteins in a single species.
      Gilts with high alloantibody reactivity to proteins in sperm membranes or lipid
      rafts produced fewer offspring (73% decrease) than adjuvant-only or nonimmune
      control animals. Alloantisera recognized more than 20 potentially unique sperm
      membrane proteins and five sperm lipid raft proteins resolved on two-dimensional
      immunoblots with or without prior enrichment by anion exchange chromatography.
      Dominant sperm membrane alloantigens identified by mass spectrometry included the
      ADAMs fertilin alpha, fertilin beta, and cyritestin. Less abundant alloantigens
      included ATP synthase F1 beta subunit, myo-inositol monophosphatase-1, and
      zymogen granule membrane glycoprotein-2. Immunodominant sperm lipid raft
      alloantigens included SAMP14, lymphocyte antigen 6K, and the epididymal sperm
      protein E12. Of the fifteen unique membrane alloantigens identified, eleven were
      known sperm-specific proteins with uncertain functions in fertilization, and four
      were not previously suspected to exist as sperm-specific isoforms. De novo
      sequences of tryptic peptides from sperm membrane alloantigen "M6" displayed no
      evident homology to known proteins, so is a newly discovered sperm-specific gene
      product in swine. We conclude that alloimmunizing gilts with sperm membranes or
      lipid rafts evokes formation of antibodies to a relatively small number of
      dominant alloantigens that include known and novel sperm-specific proteins with
      possible functions in fertilization and potential utility as targets for
      immunocontraception.

PMID- 29342177
TI  - A new fluorescent dye accumulation assay for parallel measurements of the ABCG2,
      ABCB1 and ABCC1 multidrug transporter functions.
AB  - ABC multidrug transporters are key players in cancer multidrug resistance and in
      general xenobiotic elimination, thus their functional assays provide important
      tools for research and diagnostic applications. In this study we have examined
      the potential interactions of three key human ABC multidrug transporters with
      PhenGreen diacetate (PGD), a cell permeable fluorescent metal ion indicator. The
      non-fluorescent, hydrophobic PGD rapidly enters the cells and, after cleavage by
      cellular esterases, in the absence of quenching metal ions, PhenGreen (PG)
      becomes highly fluorescent. We found that in cells expressing functional ABCG2,
      ABCB1, or ABCC1 transporters, cellular PG fluorescence is strongly reduced. This
      fluorescence signal in the presence of specific transporter inhibitors is
      increased to the fluorescence levels in the control cells. Thus the PG
      accumulation assay is a new, unique tool for the parallel determination of the
      function of the ABCG2, ABCB1, and ABCC1 multidrug transporters. Since PG has very
      low cellular toxicity, the PG accumulation assay also allows the selection,
      separation and culturing of selected cell populations expressing either of these
      transporters.

PMID- 29342178
TI  - Chaos and multi-scroll attractors in RCL-shunted junction coupled Jerk circuit
      connected by memristor.
AB  - In this paper, a new four-variable dynamical system is proposed to set chaotic
      circuit composed of memristor and Josephson junction, and the dependence of
      chaotic behaviors on nonlinearity is investigated. A magnetic flux-controlled
      memristor is used to couple with the RCL-shunted junction circuit, and the
      dynamical behaviors can be modulated by changing the coupling intensity between
      the memristor and the RCL-shunted junction. Bifurcation diagram and Lyapunov
      exponent are calculated to confirm the emergence of chaos in the improved
      dynamical system. The outputs and dynamical behaviors can be controlled by the
      initial setting and external stimulus as well. As a result, chaos can be
      suppressed and spiking occurs in the sampled outputs under negative feedback,
      while applying positive feedback type via memristor can be effective to trigger
      chaos. Furthermore, it is found that the number of multi-attractors in the Jerk
      circuit can be modulated when memristor coupling is applied on the circuit. These
      results indicate that memristor coupling can be effective to control chaotic
      circuits and it is also useful to reproduce dynamical behaviors for neuronal
      activities.

PMID- 29342179
TI  - The polymethoxy flavonoid sudachitin suppresses inflammatory bone destruction by
      directly inhibiting osteoclastogenesis due to reduced ROS production and MAPK
      activation in osteoclast precursors.
AB  - Inflammatory bone diseases, including rheumatoid arthritis, periodontitis and
      peri-implantitis, are associated not only with the production of inflammatory
      cytokines but also with local oxidative status, which is defined by intracellular
      reactive oxygen species (ROS). Osteoclast differentiation has been reported to be
      related to increased intracellular ROS levels in osteoclast lineage cells.
      Sudachitin, which is a polymethoxyflavone derived from Citrus sudachi, possesses
      antioxidant properties and regulates various functions in mammalian cells.
      However, the effects of sudachitin on inflammatory bone destruction and
      osteoclastogenesis remain unknown. In calvaria inflamed by a local
      lipopolysaccharide (LPS) injection, inflammation-induced bone destruction and the
      accompanying elevated expression of osteoclastogenesis-related genes were reduced
      by the co-administration of sudachitin and LPS. Moreover, sudachitin inhibited
      osteoclast formation in cultures of isolated osteoblasts and osteoclast
      precursors. However, sudachitin rather increased the expression of receptor
      activator of NF-kappaB ligand (RANKL), which is an important molecule triggering
      osteoclast differentiation, and the mRNA ratio of RANKL/osteoprotegerin that is a
      decoy receptor for RANKL, in the isolated osteoblasts, suggesting the presence of
      additional target cells. When osteoclast formation was induced from osteoclast
      precursors derived from bone marrow cells in the presence of soluble RANKL and
      macrophage colony-stimulating factor, sudachitin inhibited osteoclastogenesis
      without influencing cell viability. Consistently, the expression of osteoclast
      differentiation-related molecules including c-fos, NFATc1, cathepsin K and
      osteoclast fusion proteins such as DC-STAMP and Atp6v0d2 was reduced by
      sudachitin. In addition, sudachitin decreased activation of MAPKs such as Erk and
      JNK and the ROS production evoked by RANKL in osteoclast lineage cells. Our
      findings suggest that sudachitin is a useful agent for the treatment of anti
      inflammatory bone destruction.

PMID- 29342180
TI  - Increased prevalence of pregnancy and comparative risk of program attrition among
      individuals starting HIV treatment in East Africa.
AB  - BACKGROUND: The World Health Organization now recommends initiating all pregnant
      women on life-long antiretroviral therapy (ART), yet there is limited information
      about the characteristics and program outcomes of pregnant women already on ART
      in Africa. Our hypothesis was that pregnant women comprised an increasing
      proportion of those starting ART, and that sub-groups of these women were at
      higher risk for program attrition. METHODS AND FINDINGS: We used the
      International Epidemiology Databases to Evaluate AIDS- East Africa (IeDEA-EA) to
      conduct a retrospective cohort study including HIV care and treatment programs in
      Kenya, Uganda, and Tanzania. The cohort consecutively included HIV-infected
      individuals 13 years or older starting ART 2004-2014. We examined trends over
      time in the proportion pregnant, their characteristics and program attrition
      rates compared to others initiating and already receiving ART. 156,474 HIV
      infected individuals (67.0% women) started ART. The proportion of individuals
      starting ART who were pregnant women rose from 5.3% in 2004 to 12.2% in 2014.
      Mean CD4 cell counts at ART initiation, weighted for annual program size,
      increased from 2004 to 2014, led by non-pregnant women (annual increase 20
      cells/mm3) and men (17 cells/mm3 annually), with lower rates of change in
      pregnant women (10 cells/mm3 per year) (p<0.0001). There was no significant
      difference in the cumulative incidence of program attrition at 6 months among
      pregnant women starting ART and non-pregnant women. However, healthy pregnant
      women starting ART (WHO stage 1/2) had a higher rate of attrition rate (9.6%),
      compared with healthy non-pregnant women (6.5%); in contrast among women with WHO
      stage 3/4 disease, pregnant women had lower attrition (8.4%) than non-pregnant
      women (14.4%). Among women who initiated ART when healthy and remained in care
      for six months, subsequent six-month attrition was slightly higher among pregnant
      women at ART start (3.5%) compared to those who were not pregnant (2.4%),
      (absolute difference 1.1%, 95% CI 0.7%-1.5%). CONCLUSIONS: Pregnant women
      comprise an increasing proportion of those initiating ART in Africa, and pregnant
      women starting ART while healthy are at higher risk for program attrition than
      non-pregnant women. As ART programs further expand access to healthier pregnant
      women, further studies are needed to better understand the drivers of loss among
      this high risk group of women to optimize retention.

PMID- 29342181
TI  - Optimization of mNeonGreen for Homo sapiens increases its fluorescent intensity
      in mammalian cells.
AB  - Green fluorescent protein (GFP) is tremendously useful for investigating many
      cellular and intracellular events. The monomeric GFP mNeonGreen is about 3- to 5
      times brighter than GFP and monomeric enhanced GFP and shows high photostability.
      The maturation half-time of mNeonGreen is about 3-fold faster than that of
      monomeric enhanced GFP. However, the cDNA sequence encoding mNeonGreen contains
      some codons that are rarely used in Homo sapiens. For better expression of
      mNeonGreen in human cells, we synthesized a human-optimized cDNA encoding
      mNeonGreen and generated an expression plasmid for humanized mNeonGreen under the
      control of the cytomegalovirus promoter. The resultant plasmid was introduced
      into HEK293 cells. The fluorescent intensity of humanized mNeonGreen was about
      1.4-fold higher than that of the original mNeonGreen. The humanized mNeonGreen
      with a mitochondria-targeting signal showed mitochondrial distribution of
      mNeonGreen. We further generated an expression vector of humanized mNeonGreen
      with 3xFLAG tags at its carboxyl terminus as these tags are useful for
      immunological analyses. The 3xFLAG-tagged mNeonGreen was recognized well with an
      anti-FLAG-M2 antibody. These plasmids for the expression of humanized mNeonGreen
      and mNeonGreen-3xFLAG are useful tools for biological studies in mammalian cells
      using mNeonGreen.

PMID- 29342182
TI  - Light alcohol consumption has the potential to suppress hepatocellular injury and
      liver fibrosis in non-alcoholic fatty liver disease.
AB  - BACKGROUND & AIMS: The modest consumption of alcohol has been reported to
      decrease the incidence of fatty liver or prevalence of steatohepatitis. In this
      study, we investigated the effect of light alcohol consumption on liver function
      and gene expression in patients with non-alcoholic fatty liver disease (NAFLD).
      METHODS: The study group was formed of 178 patients diagnosed with non-alcoholic
      fatty liver disease, subclassified into two groups for analysis based on the
      daily alcohol consumption: non-alcohol group and light alcohol consumer group
      (<=20 g of ethanol/day). Clinical characteristics, liver histological features,
      gene expression, comprehensively analyzed using microarrays (BRB-Array tools),
      and molecular network were evaluated and compared between the two groups.
      RESULTS: No significant differences in steatosis or inflammation score were noted
      among the groups. However, the ballooning and fibrosis scores were significantly
      lower in the light alcohol consumer group than in the non-alcohol group. Gene
      expression analysis revealed a marked inhibition of the pathways involved in the
      immune response in the light alcohol group compared to that in the non-alcohol
      group. CONCLUSIONS: Light alcohol consumption might suppress activity of non
      alcoholic steatohepatitis by reducing gene expression levels involved in the
      immune response. This inhibition in gene expression was associated with a
      lowering of liver fibrosis and hepatocellular injury.

PMID- 29342183
TI  - Identification of volatiles released by diapausing brown marmorated stink bug,
      Halyomorpha halys (Hemiptera: Pentatomidae).
AB  - The brown marmorated stink bug, Halyomorpha halys, is an agricultural and urban
      pest that has become widely established as an invasive species of major concern
      in the USA and across Europe. This species forms large aggregations when entering
      diapause, and it is often these aggregations that are found by officials
      conducting inspections of internationally shipped freight. Identifying the
      presence of diapausing aggregations of H. halys using their emissions of volatile
      organic compounds (VOCs) may be a potential means for detecting and intercepting
      them during international freight inspections. Headspace samples were collected
      from aggregations of diapausing H. halys using volatile collection traps (VCTs)
      and solid phase microextraction. The only compound detected in all samples was
      tridecane, with small amounts of (E)-2-decenal found in most samples. We also
      monitored the release of defensive odors, following mechanical agitation of
      diapausing and diapause-disrupted adult H. halys. Diapausing groups were
      significantly more likely to release defensive odors than diapause-disrupted
      groups. The predominant compounds consistently found from both groups were
      tridecane, (E)-2-decenal, and 4-oxo-(E)-2-hexenal, with a small abundance of
      dodecane. Our findings show that diapausing H. halys do release defensive
      compounds, and suggest that volatile sampling may be feasible to detect H. halys
      in freight.

PMID- 29342184
TI  - Species delimitation in the Stenocereus griseus (Cactaceae) species complex
      reveals a new species, S. huastecorum.
AB  - The Stenocereus griseus species complex (SGSC) has long been considered
      taxonomically challenging because the number of taxa belonging to the complex and
      their geographical boundaries remain poorly understood. Bayesian clustering and
      genetic distance-based methods were used based on nine microsatellite loci in 377
      individuals of three main putative species of the complex. The resulting genetic
      clusters were assessed for ecological niche divergence and areolar morphology,
      particularly spination patterns. We based our species boundaries on concordance
      between genetic, ecological, and morphological data, and were able to resolve
      four species, three of them corresponding to S. pruinosus from central Mexico, S.
      laevigatus from southern Mexico, and S. griseus from northern South America. A
      fourth species, previously considered to be S. griseus and commonly misidentified
      as S. pruinosus in northern Mexico showed significant genetic, ecological, and
      morphological differentiation suggesting that it should be considered a new
      species, S. huastecorum, which we describe here. We show that population genetic
      analyses, ecological niche modeling, and morphological studies are complementary
      approaches for delimiting species in taxonomically challenging plant groups such
      as the SGSC.

PMID- 29342185
TI  - Nanocarrier-mediated foliar zinc fertilization influences expression of metal
      homeostasis related genes in flag leaves and enhances gluten content in durum
      wheat.
AB  - BACKGROUND: Wheat is the staple food for most of the world's population; however,
      it is a poor source of zinc. Foliar fertilization of zinc via zinc loaded
      chitosan nanocarriers (Zn-CNP) post-anthesis has proved to be a promising
      approach for grain zinc enhancement in durum wheat as evidenced in our earlier
      study. However, the molecular mechanism of uptake of zinc via Zn-CNP remains
      unclear. METHODS/PRINCIPLE FINDINGS: Foliar application of Zn-CNP was performed
      at post anthesis stages in two durum wheat cultivars (MACS 3125 and UC1114,
      containing the Gpc-B1 gene), and expression levels of several metal-related genes
      were analyzed during early senescence. Zn-CNP application indeed caused changes
      in gene expression as revealed by qPCR data on representative genes involved in
      metal homeostasis, phloem transporters, and leaf senescence. Furthermore, zinc
      regulated transporters and iron (Fe)-regulated transporter-like protein (ZIP)
      family [ZIP1, ZIP7, ZIP15], CA (carbonic anhydrase), and DMAS (2'-deoxymugineic
      acid synthase) in flag leaves exhibited significant correlation with zinc content
      in the seeds. The analysis of grain endosperm proteins showed enhancement of
      gamma gliadins while other gluten subunits decreased. Gene expression within ZIP
      family members varied with the type of cultivar mostly attributed to the Gpc-B1,
      concentration of external zinc ions as well as the type of tissue analyzed.
      Correlation analysis revealed the involvement of the selected genes in zinc
      enhancement. CONCLUSION: At the molecular level, uptake of zinc via Zn-CNP
      nanocarrier was comparable to the uptake of zinc via common zinc fertilizers i.e.
      ZnSO4.

PMID- 29342186
TI  - Doxorubicin-provoked increase of mitotic activity and concomitant drain of G0
      pool in therapy-resistant BE(2)-C neuroblastoma.
AB  - In this study chemotherapy response in neuroblastoma (NB) was assessed for the
      first time in a transplantation model comprising non-malignant human embryonic
      microenvironment of pluripotent stem cell teratoma (PSCT) derived from diploid
      bona fide hESC. Two NB cell lines with known high-risk phenotypes; the multi
      resistant BE(2)-C and the drug sensitive IMR-32, were transplanted to the PSCT
      model and the tumour growth was exposed to single or repeated treatments with
      doxorubicin, and thereafter evaluated for cell death, apoptosis, and
      proliferation. Dose dependent cytotoxic effects were observed, this way
      corroborating the experimental platform for this type of analysis. Notably,
      analysis of doxorubicin-resilient BE(2)-C growth in the PSCT model revealed an
      unexpected 1,5-fold increase in Ki67-index (p<0.05), indicating that non-cycling
      (G0) cells entered the cell cycle following the doxorubicin exposure. Support for
      this notion was obtained also in vitro. A pharmacologically relevant dose (1MUM)
      resulted in a marked accumulation of Ki67 positive BE(2)-C cells (p<0.0001), as
      well as a >3-fold increase in active cell cycle (i.e. cells positive staining for
      PH3 together with incorporation of EdU) (p<0.01). Considering the clinical
      challenge for treating high-risk NB, the discovery of a therapy-provoked growth
      stimulating effect in the multi-resistant and p53-mutated BE(2)-C cell line, but
      not in the drug-sensitive p53wt IMR-32 cell line, warrants further studies
      concerning generality and clinical significance of this new observation.

PMID- 29342187
TI  - Induction of high tolerance to artemisinin by sub-lethal administration: A new in
      vitro model of P. falciparum.
AB  - Artemisinin resistance is a major threat to malaria control efforts. Resistance
      is characterized by an increase in the Plasmodium falciparum parasite clearance
      half-life following treatment with artemisinin-based combination therapies (ACTs)
      and an increase in the percentage of surviving parasites. The remarkably short
      blood half-life of artemisinin derivatives may contribute to drug-resistance,
      possibly through factors including sub-lethal plasma concentrations and
      inadequate exposure. Here we selected for a new strain of artemisinin resistant
      parasites, termed the artemisinin resistant strain 1 (ARS1), by treating P.
      falciparum Palo Alto (PA) cultures with sub-lethal concentrations of
      dihydroartemisinin (DHA). The resistance phenotype was maintained for over 1 year
      through monthly maintenance treatments with low doses of 2.5 nM DHA. There was a
      moderate increase in the DHA IC50 in ARS1 when compared with parental strain PA
      after 72 h of drug exposure (from 0.68 nM to 2 nM DHA). In addition, ARS1
      survived treatment physiologically relevant DHA concentrations (700 nM) observed
      in patients. Furthermore, we confirmed a lack of cross-resistance against a panel
      of antimalarials commonly used as partner drugs in ACTs. Finally, ARS1 did not
      contain Pfk13 propeller domain mutations associated with ART resistance in the
      Greater Mekong Region. With a stable growth rate, ARS1 represents a valuable tool
      for the development of new antimalarial compounds and studies to further
      elucidate the mechanisms of ART resistance.

PMID- 29342188
TI  - Comparative analysis of gene expression identifies distinct molecular signatures
      of bone marrow- and periosteal-skeletal stem/progenitor cells.
AB  - Periosteum and bone marrow (BM) both contain skeletal stem/progenitor cells
      (SSCs) that participate in fracture repair. However, the functional difference
      and selective regulatory mechanisms of SSCs in different locations are unknown
      due to the lack of specific markers. Here, we report a comprehensive gene
      expression analysis of bone marrow SSCs (BM-SSCs), periosteal SSCs (P-SSCs), and
      more differentiated osteoprogenitors by using reporter mice expressing Interferon
      inducible Mx1 and NestinGFP, previously known SSC markers. We first defined that
      the BM-SSCs can be enriched by the combination of Mx1 and NestinGFP expression,
      while endogenous P-SSCs can be isolated by positive selection of Mx1, CD105 and
      CD140a (known SSC markers) combined with the negative selection of CD45, CD31,
      and osteocalcinGFP (a mature osteoblast marker). Comparative gene expression
      analysis with FACS-sorted BM-SSCs, P-SSCs, Osterix+ preosteoblasts, CD51+ stroma
      cells and CD45+ hematopoietic cells as controls revealed that BM-SSCs and P-SSCs
      have high similarity with few potential differences without statistical
      significance. We also found that CD51+ cells are highly heterogeneous and have
      little overlap with SSCs. This was further supported by the microarray cluster
      analysis, where the two SSC populations clustered together but are separate from
      the CD51+ cells. However, when comparing SSC population to controls, we found
      several genes that are uniquely upregulated in endogenous SSCs. Amongst these
      genes, we found KDR (aka Flk1 or VEGFR2) to be most interesting and discovered
      that it is highly and selectively expressed in P-SSCs. This finding suggests that
      endogenous P-SSCs are functionally very similar to BM-SSCs with undetectable
      significant differences in gene expression but there are distinct molecular
      signatures in P-SSCs, which can be useful to specify P-SSC subset in vivo.

PMID- 29342190
TI  - Potential of vegetation indices combined with laser-induced fluorescence
      parameters for monitoring leaf nitrogen content in paddy rice.
AB  - Nitrogen (N) is important for the growth of crops. Leaf nitrogen content (LNC)
      serves as a crucial indicator of the growth status of crops and can help
      determine the dose of N fertilizer. Laser-induced fluorescence (LIF) technology
      and the reflectance spectra of crops are widely used to detect the biochemical
      content of leaves. Many vegetation indices (VIs) and fluorescence parameters have
      been developed to estimate LNC. However, the comparison among VIs and between
      fluorescence parameters and VIs has been rarely studied in the estimation of LNC.
      In this study, the performances of several published empirical VIs and
      fluorescence parameters for the estimation of paddy rice LNC were analyzed using
      the support vector machine (SVM) algorithm. Then, the optimal VIs (TVI, MTVI1,
      MTVI2, and MSAVI) and fluorescence parameters (F735/F460 and F685/F460), which
      were suitable for LNC monitoring in this study, were chosen. In addition, the
      combination of the VIs and fluorescence parameters was proposed as the input
      variables in the SVM model and used to estimate the LNC. Experimental results
      exhibited the promising potential of the LIF technology combined with reflectance
      for the accurate estimation of LNC, which provided guidance for monitoring the
      LNC.

PMID- 29342189
TI  - The microbiota metabolite indole inhibits Salmonella virulence: Involvement of
      the PhoPQ two-component system.
AB  - The microbial community present in the gastrointestinal tract is an important
      component of the host defense against pathogen infections. We previously
      demonstrated that indole, a microbial metabolite of tryptophan, reduces
      enterohemorrhagic Escherichia coli O157:H7 attachment to intestinal epithelial
      cells and biofilm formation, suggesting that indole may be an effector/attenuator
      of colonization for a number of enteric pathogens. Here, we report that indole
      attenuates Salmonella Typhimurium (Salmonella) virulence and invasion as well as
      increases resistance to colonization in host cells. Indole-exposed Salmonella
      colonized mice less effectively compared to solvent-treated controls, as evident
      by competitive index values less than 1 in multiple organs. Indole-exposed
      Salmonella demonstrated 160-fold less invasion of HeLa epithelial cells and 2
      fold less invasion of J774A.1 macrophages compared to solvent-treated controls.
      However, indole did not affect Salmonella intracellular survival in J774A.1
      macrophages suggesting that indole primarily affects Salmonella invasion. The
      decrease in invasion was corroborated by a decrease in expression of multiple
      Salmonella Pathogenicity Island-1 (SPI-1) genes. We also identified that the
      effect of indole was mediated by both PhoPQ-dependent and independent mechanisms.
      Indole also synergistically enhanced the inhibitory effect of a short chain fatty
      acid cocktail on SPI-1 gene expression. Lastly, indole-treated HeLa cells were
      70% more resistant to Salmonella invasion suggesting that indole also increases
      resistance of epithelial cells to colonization. Our results demonstrate that
      indole is an important microbiota metabolite that has direct anti-infective
      effects on Salmonella and host cells, revealing novel mechanisms of pathogen
      colonization resistance.

PMID- 29342191
TI  - Changes in balance and joint position sense during a 12-day high altitude trek:
      The British Services Dhaulagiri medical research expedition.
AB  - Postural control and joint position sense are essential for safely undertaking
      leisure and professional activities, particularly at high altitude. We tested
      whether exposure to a 12-day trek with a gradual ascent to high altitude impairs
      postural control and joint position sense. This was a repeated measures
      observational study of 12 military service personnel (28+/-4 years). Postural
      control (sway velocity measured by a portable force platform) during standing
      balance, a Sharpened Romberg Test and knee joint position sense were measured, in
      England (113m elevation) and at 3 research camps (3619m, 4600m and 5140m) on a 12
      day high altitude trek in the Dhaulagiri region of Nepal. Pulse oximetry, and
      Lake Louise scores were also recorded on the morning and evening of each trek
      day. Data were compared between altitudes and relationships between pulse
      oximetry, Lake Louise score, and sway velocity were explored. Total sway velocity
      during standing balance with eyes open (p = 0.003, d = 1.9) and during Sharpened
      Romberg test with eyes open (p = 0.007, d = 1.6) was significantly greater at
      altitudes of 3619m and 5140m when compared with sea level. Anterior-posterior
      sway velocity during standing balance with eyes open was also significantly
      greater at altitudes of 3619m and 5140m when compared with sea level (p = 0.001,
      d = 1.9). Knee joint position sense was not altered at higher altitudes. There
      were no significant correlations between Lake Louise scores, pulse oximetry and
      postural sway. Despite a gradual ascent profile, exposure to 3619 m was
      associated with impairments in postural control without impairment in knee joint
      position sense. Importantly, these impairments did not worsen at higher altitudes
      of 4600 m or 5140 m. The present findings should be considered during future
      trekking expeditions when developing training strategies targeted to manage
      impairments in postural control that occur with increasing altitude.

PMID- 29342192
TI  - White matter tract-specific quantitative analysis in multiple sclerosis:
      Comparison of optic radiation reconstruction techniques.
AB  - The posterior visual pathway is commonly affected by multiple sclerosis (MS)
      pathology that results in measurable clinical and electrophysiological
      impairment. Due to its highly structured retinotopic mapping, the visual pathway
      represents an ideal substrate for investigating patho-mechanisms in MS.
      Therefore, a reliable and robust imaging segmentation method for in-vivo
      delineation of the optic radiations (OR) is needed. However, diffusion-based
      tractography approaches, which are typically used for OR segmentation are
      confounded by the presence of focal white matter lesions. Current solutions
      require complex acquisition paradigms and demand expert image analysis, limiting
      application in both clinical trials and clinical practice. In the current study,
      using data acquired in a clinical setting on a 3T scanner, we optimised and
      compared two approaches for optic radiation (OR) reconstruction: individual
      probabilistic tractography-based and template-based methods. OR segmentation
      results were applied to subjects with MS and volumetric and diffusivity
      parameters were compared between OR segmentation techniques. Despite differences
      in reconstructed OR volumes, both OR lesion volume and OR diffusivity
      measurements in MS subjects were highly comparable using optimised probabilistic
      tractography-based, and template-based, methods. The choice of OR reconstruction
      technique should be determined primarily by the research question and the nature
      of the available dataset. Template-based approaches are particularly suited to
      the semi-automated analysis of large image datasets and have utility even in the
      absence of dMRI acquisitions. Individual tractography methods, while more complex
      than template based OR reconstruction, permit measurement of diffusivity changes
      along fibre bundles that are affected by specific MS lesions or other focal
      pathologies.

PMID- 29342193
TI  - Analysis of copy number loss of the ErbB4 receptor tyrosine kinase in
      glioblastoma.
AB  - Current treatments for glioblastoma multiforme (GBM)-an aggressive form of brain
      cancer-are minimally effective and yield a median survival of 14.6 months and a
      two-year survival rate of 30%. Given the severity of GBM and the limitations of
      its treatment, there is a need for the discovery of novel drug targets for GBM
      and more personalized treatment approaches based on the characteristics of an
      individual's tumor. Most receptor tyrosine kinases-such as EGFR-act as oncogenes,
      but publicly available data from the Cancer Cell Line Encyclopedia (CCLE)
      indicates copy number loss in the ERBB4 RTK gene across dozens of GBM cell lines,
      suggesting a potential tumor suppressor role. This loss is mutually exclusive
      with loss of its cognate ligand NRG1 in CCLE as well, more strongly suggesting a
      functional role. The availability of higher resolution copy number data from
      clinical GBM patients in The Cancer Genome Atlas (TCGA) revealed that a region in
      Intron 1 of the ERBB4 gene was deleted in 69.1% of tumor samples harboring ERBB4
      copy number loss; however, it was also found to be deleted in the matched normal
      tissue samples from these GBM patients (n = 81). Using the DECIPHER Genome
      Browser, we also discovered that this mutation occurs at approximately the same
      frequency in the general population as it does in the disease population. We
      conclude from these results that this loss in Intron 1 of the ERBB4 gene is
      neither a de novo driver mutation nor a predisposing factor to GBM, despite the
      indications from CCLE. A biological role of this significantly occurring genetic
      alteration is still unknown. While this is a negative result, the broader
      conclusion is that while copy number data from large cell line-based data
      repositories may yield compelling hypotheses, careful follow up with higher
      resolution copy number assays, patient data, and general population analyses are
      essential to codify initial hypotheses prior to investing experimental resources.

PMID- 29342194
TI  - Tolerance to mild salinity stress in japonica rice: A genome-wide association
      mapping study highlights calcium signaling and metabolism genes.
AB  - Salinity tolerance is an important quality for European rice grown in river
      deltas. We evaluated the salinity tolerance of a panel of 235 temperate japonica
      rice accessions genotyped with 30,000 SNP markers. The panel was exposed to mild
      salt stress (50 mM NaCl; conductivity of 6 dS m-1) at the seedling stage. Eight
      different root and shoot growth parameters were measured for both the control and
      stressed treatments. The Na+ and K+ mass fractions of the stressed plants were
      measured using atomic absorption spectroscopy. The salt treatment affected plant
      growth, particularly the shoot parameters. The panel showed a wide range of
      Na+/K+ ratio and the temperate accessions were distributed over an increasing
      axis, from the most resistant to the most susceptible checks. We conducted a
      genome-wide association study on indices of stress response and ion mass
      fractions in the leaves using a classical mixed model controlling structure and
      kinship. A total of 27 QTLs validated by sub-sampling were identified. For
      indices of stress responses, we also used another model that focused on marker *
      treatment interactions and detected 50 QTLs, three of which were also identified
      using the classical method. We compared the positions of the significant QTLs to
      those of approximately 300 genes that play a role in rice salt tolerance. The
      positions of several QTLs were close to those of genes involved in calcium
      signaling and metabolism, while other QTLs were close to those of kinases. These
      results reveal the salinity tolerance of accessions with a temperate japonica
      background. Although the detected QTLs must be confirmed by other approaches, the
      number of associations linked to candidate genes involved in calcium-mediated ion
      homeostasis highlights pathways to explore in priority to understand the salinity
      tolerance of temperate rice.

PMID- 29342195
TI  - Association between PM10, PM2.5, NO2, O3 and self-reported diabetes in Italy: A
      cross-sectional, ecological study.
AB  - INTRODUCTION: Air pollution represents a serious threat to health on a global
      scale, being responsible for a large portion of the global burden of disease from
      environmental factors. Current evidence about the association between air
      pollution exposure and Diabetes Mellitus (DM) is still controversial. We aimed to
      evaluate the association between area-level ambient air pollution and self
      reported DM in a large population sample in Italy. MATERIALS AND METHODS: We
      extracted information about self-reported and physician diagnosed DM, risk
      factors and socio-economic status from 12 surveys conducted nationwide between
      1999 and 2013. We obtained annual averaged air pollution levels for the years
      2003, 2005, 2007 and 2010 from the AMS-MINNI national integrated model, which
      simulates the dispersion and transformation of pollutants. The original maps,
      with a resolution of 4 x 4 km2, were normalized and aggregated at the
      municipality class of each Italian region, in order to match the survey data. We
      fit logistic regression models with a hierarchical structure to estimate the
      relationship between PM10, PM2.5, NO2 and O3 four-years mean levels and the risk
      of being affected by DM. RESULTS: We included 376,157 individuals aged more than
      45 years. There were 39,969 cases of DM, with an average regional prevalence of
      9.8% and a positive geographical North-to-South gradient, opposite to that of
      pollutants' concentrations. For each 10 MUg/m3 increase, the resulting ORs were
      1.04 (95% CI 1.01-1.07) for PM10, 1.04 (95% CI 1.02-1.07) for PM2.5, 1.03 (95% CI
      1.01-1.05) for NO2 and 1.06 (95% CI 1.01-1.11) for O3, after accounting for
      relevant individual risk factors. The associations were robust to adjustment for
      other pollutants in two-pollutant models tested (ozone plus each other
      pollutant). CONCLUSIONS: We observed a significant positive association between
      each examined pollutant and prevalent DM. Risk estimates were consistent with
      current evidence, and robust to sensitivity analysis. Our study adds evidence
      about the effects of air pollution on diabetes and suggests a possible role of
      ozone as an independent factor associated with the development of DM. Such
      relationship is of great interest for public health and deserves further
      investigation.

PMID- 29342196
TI  - Low fitness is associated with abdominal adiposity and low-grade inflammation
      independent of BMI.
AB  - OBJECTIVE: Up to 30% of obese individuals are metabolically healthy.
      Metabolically healthy obese (MHO) individuals are characterized by having low
      abdominal adiposity, low inflammation level and low risk of developing metabolic
      comorbidity. In this study, we hypothesize that cardiorespiratory fitness
      (fitness) is a determinant factor for the MHO individuals and aim to investigate
      the associations between fitness, abdominal adiposity and low-grade inflammation
      within different BMI categories. METHOD: Data from 10,976 individuals from the
      general population, DANHES 2007-2008, on waist circumference, fitness and C
      reactive protein (hsCRP) were analysed using multiple linear and median quantile
      regressions. RESULTS: In men, an inverse association between fitness (+5 mL min-1
      kg-1) and waist circumference (-1.45 cm; 95% CI: -1.55 to -1.35 cm; p<0.001), and
      an inverse association between fitness (+5 mL min-1 kg-1) and hsCRP (-0.22 mg/L;
      95% CI: -0.255 to -0.185 mg/L; p<0.001) was found, all independent of BMI.
      Similarly in women, an inverse association between fitness (+5 mL min-1 kg-1) and
      waist circumference (-1.15 cm; 95% CI: -1.25 to -1.0 cm; p<0.001), and an inverse
      association between fitness (+5 mL min-1 kg-1) and hsCRP (-0.26 mg/L; 95% CI: 
      0.3 to -0.22 mg/L; p<0.001) was found, all independent of BMI. Additionally,
      significant positive associations between waist circumference and hsCRP were
      found for both men and women, independently of BMI. CONCLUSION: Fitness was found
      to be inversely associated with both abdominal adiposity and low-grade
      inflammation independent of BMI. These data suggest that, in spite of BMI, high
      fitness levels lead to a reduction in abdominal fat mass and low-grade
      inflammation.

PMID- 29342197
TI  - Molecular discrimination of tall fescue morphotypes in association with Festuca
      relatives.
AB  - Tall fescue (Festuca arundinacea Schreb.) is an important cool-season perennial
      grass species used as forage and turf, and in conservation plantings. There are
      three morphotypes in hexaploid tall fescue: Continental, Mediterranean and
      Rhizomatous. This study was conducted to develop morphotype-specific molecular
      markers to distinguish Continental and Mediterranean tall fescues, and establish
      their relationships with other species of the Festuca genus for genomic
      inference. Chloroplast sequence variation and simple sequence repeat (SSR)
      polymorphism were explored in 12 genotypes of three tall fescue morphotypes and
      four Festuca species. Hypervariable chloroplast regions were retrieved by using
      33 specifically designed primers followed by sequencing the PCR products. SSR
      polymorphism was studied using 144 tall fescue SSR primers. Four chloroplast
      (NFTCHL17, NFTCHL43, NFTCHL45 and NFTCHL48) and three SSR (nffa090, nffa204 and
      nffa338) markers were identified which can distinctly differentiate Continental
      and Mediterranean morphotypes. A primer pair, NFTCHL45, amplified a 47 bp
      deletion between the two morphotypes is being routinely used in the Noble
      Research Institute's core facility for morphotype discrimination. Both
      chloroplast sequence variation and SSR diversity showed a close association
      between Rhizomatous and Continental morphotypes, while the Mediterranean
      morphotype was in a distant clade. F. pratensis and F. arundinacea var.
      glaucescens, the P and G1G2 genome donors, respectively, were grouped with the
      Continental clade, and F. mairei (M1M2 genome) grouped with the Mediterranean
      clade in chloroplast sequence variation, while both F. pratensis and F. mairei
      formed independent clade in SSR analysis. Age estimation based on chloroplast
      sequence variation indicated that the Continental and Mediterranean clades might
      have been colonized independently during 0.65 +/- 0.06 and 0.96 +/- 0.1 million
      years ago (Mya) respectively. The findings of the study will enhance tall fescue
      breeding for persistence and productivity.

PMID- 29342198
TI  - Three-dimensional printing model improves morphological understanding in
      acetabular fracture learning: A multicenter, randomized, controlled study.
AB  - Conventional education results in unsatisfactory morphological understanding of
      acetabular fractures due to lack of three-dimensional (3D) details and tactile
      feedback of real fractures. Virtual reality (VR) and 3D printing (3DP) techniques
      are widely applied in teaching. The purpose of this study was to identify the
      effect of physical model (PM), VR and 3DP models in education of morphological
      understanding of acetabular fractures. 141 students were invited to participate
      in this study. Participants were equally and randomly assigned to the PM, VR and
      3DP learning groups. Three-level objective tests were conducted to evaluate
      learning, including identifying anatomical landmarks, describing fracture lines,
      identifying classification, and inferring fracture mechanism. Four subjective
      questions were asked to evaluate the usability and value of instructional
      materials. Generally, the 3DP group showed a clear advantage over the PM and VR
      groups in objective tests, while there was no significant difference between the
      PM and VR groups. 3DP was considered to be the most valuable learning tool for
      understanding acetabular fractures. The findings demonstrate that 3DP modelling
      of real fractures is an effective learning instrument that can be used to
      understand the morphology of acetabular fractures and promote subjective
      interest.

PMID- 29342199
TI  - A non-linear pharmacokinetic-pharmacodynamic relationship of metformin in healthy
      volunteers: An open-label, parallel group, randomized clinical study.
AB  - BACKGROUND: The aim of this study was to explore the pharmacokinetic
      pharmacodynamic (PK-PD) relationship of metformin on glucose levels after the
      administration of 250 mg and 1000 mg of metformin in healthy volunteers. METHODS:
      A total of 20 healthy male volunteers were randomized to receive two doses of
      either a low dose (375 mg followed by 250 mg) or a high dose (1000 mg followed by
      1000 mg) of metformin at 12-h intervals. The pharmacodynamics of metformin was
      assessed using oral glucose tolerance tests before and after metformin
      administration. The PK parameters after the second dose were evaluated through
      noncompartmental analyses. Four single nucleotide polymorphisms in MATE1, MATE2
      K, and OCT2 were genotyped, and their effects on PK characteristics were
      additionally evaluated. RESULTS: The plasma exposure of metformin increased as
      the metformin dose increased. The mean values for the area under the
      concentration-time curve from dosing to 12 hours post-dose (AUC0-12h) were 3160.4
      and 8808.2 h.MUg/L for the low- and high-dose groups, respectively. Non-linear
      relationships were found between the glucose-lowering effect and PK parameters
      with a significant inverse trend at high metformin exposure. The PK parameters
      were comparable among subjects with the genetic polymorphisms. CONCLUSIONS: This
      study showed a non-linear PK-PD relationship on plasma glucose levels after the
      administration of metformin. The inverse relationship between systemic exposure
      and the glucose-lowering effect at a high exposure indicates a possible role for
      the intestines as an action site for metformin. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT02712619.

PMID- 29342200
TI  - Inhibiting TGF-beta signaling preserves the function of highly activated, in
      vitro expanded natural killer cells in AML and colon cancer models.
AB  - Natural killer cells harnessed from healthy individuals can be expanded ex vivo
      using various platforms to produce large doses for adoptive transfer into cancer
      patients. During such expansion, NK cells are increasingly activated and more
      efficient at killing cancer cells. Adoptive transfer however introduces these
      activated cells into a highly immunosuppressive tumor microenvironment mediated
      in part by excessive transforming growth factor beta (TGF-beta) from both cancer
      cells and their surrounding stroma. This microenvironment ultimately limits the
      clinical efficacy of NK cell therapy. In this study, we examined the use of a TGF
      beta receptor kinase inhibitor, LY2157299, in preserving the cytotoxic function
      of ex vivo expanded, highly activated NK cells following sustained exposure to
      pathologic levels of TGF-beta in vitro and in a liver metastases model of colon
      cancer. Using myeloid leukemia and colon cancer cell lines, we show that the TGF
      beta driven impairment of NK cell cytotoxicity is mitigated by LY2157299. We
      demonstrate this effect using quantitative cytotoxicity assays as well as by
      showing a preserved activated phenotype with high NKG2D/CD16 expression and
      enhanced cytokine production. In a mouse liver metastases model of colon cancer,
      we observed significantly improved eradication of liver metastases in mice
      treated with adoptive NK cells combined with LY2157299 compared with mice
      receiving NK cells or TGF beta inhibition alone. We propose that the therapeutic
      efficacy of adoptive NK cell therapy clinically will be markedly enhanced by
      complementary approaches targeting TGF-beta signaling in vivo.

PMID- 29342201
TI  - Differentiation of glioblastoma multiforme, metastases and primary central
      nervous system lymphomas using multiparametric perfusion and diffusion MR imaging
      of a tumor core and a peritumoral zone-Searching for a practical approach.
AB  - INTRODUCTION: In conventional MR examinations glioblastomas multiforme (GBMs),
      metastases and primary CNS lymphomas (PCNSLs) may show very similar appearance.
      The aim of the study was to evaluate usefulness of multiparametric T2*DSC
      perfusion and diffusion MR imaging in the preoperative differentiation of these
      tumors. MATERIAL AND METHODS: Seventy four solitary enhancing tumors (27 GBMs, 30
      metastases, 17 PCNSLs) were enrolled in the study. Parameters of cerebral blood
      volume (rCBV), peak height (rPH), percentage of signal recovery (rPSR) and
      apparent diffusion coefficient (ADC) were assessed from the tumor core and the
      peritumoral non-enhancing T2-hyperintense zone. RESULTS: Within the tumor core
      there were no differences in perfusion and diffusion parameters between GBMs and
      metastases. Compared to GBMs and metastases, PCNSLs showed significantly lower
      rCBV and rPH, ADC as well as higher rPSR values. Max rCBV with a cut-off value of
      2.18 demonstrated the highest accuracy of 0.98 in differentiating PCNSLs from
      other tumors. To distinguish GBMs from metastases analysis of the peritumoral
      zone was performed showing significantly higher rCBV, rPH and lower ADC values in
      GBMs with the highest accuracy of 0.94 found for max rCBV at a cut-off value of
      0.98. CONCLUSIONS: Max rCBV seems to be the most important parameter to
      differentiate GBMs, metastases and PCNSLs. Analysis of max rCBV within the tumor
      core enables to distinguish hypoperfused PCNSLs from hyperperfused GBMs and
      metastases while evaluation of max rCBV within the peritumoral zone is helpful to
      distinguish GBMs showing peritumoral infiltration from metastases surrounded by
      pure edema.

PMID- 29342202
TI  - Cells containing aragonite crystals mediate responses to gravity in Trichoplax
      adhaerens (Placozoa), an animal lacking neurons and synapses.
AB  - Trichoplax adhaerens has only six cell types. The function as well as the
      structure of crystal cells, the least numerous cell type, presented an enigma.
      Crystal cells are arrayed around the perimeter of the animal and each contains a
      birefringent crystal. Crystal cells resemble lithocytes in other animals so we
      looked for evidence they are gravity sensors. Confocal microscopy showed that
      their cup-shaped nuclei are oriented toward the edge of the animal, and that the
      crystal shifts downward under the influence of gravity. Some animals
      spontaneously lack crystal cells and these animals behaved differently upon being
      tilted vertically than animals with a typical number of crystal cells. EM
      revealed crystal cell contacts with fiber cells and epithelial cells but these
      contacts lacked features of synapses. EM spectroscopic analyses showed that
      crystals consist of the aragonite form of calcium carbonate. We thus provide
      behavioral evidence that Trichoplax are able to sense gravity, and that crystal
      cells are likely to be their gravity receptors. Moreover, because placozoans are
      thought to have evolved during Ediacaran or Cryogenian eras associated with
      aragonite seas, and their crystals are made of aragonite, they may have acquired
      gravity sensors during this early era.

PMID- 29342203
TI  - Biological pathways underlying the association of red cell distribution width and
      adverse clinical outcome: Results of a prospective cohort study.
AB  - BACKGROUND: Red cell distribution width (RDW) predicts disease outcome in several
      patient populations, but its prognostic value in addition to other disease
      parameters in unselected medical inpatients remains unclear. Our aim was to
      investigate the association of admission RDW levels and mortality adjusted for
      several disease pathways in unselected medical patients from a previous
      multicenter study. METHODS: We included consecutive adult, medical patients at
      the time point of hospital admission through the emergency department into this
      observational, cohort study. The primary endpoint was mortality at 30-day. To
      study association of admission RDW and outcomes, we calculated regression
      analysis with step-wise inclusion of clinical and laboratory parameters from
      different biological pathways. RESULTS: The 30-day mortality of the 4273 included
      patients was 5.6% and increased from 1.4% to 14.3% from the lowest to the highest
      RDW quartile. There was a strong association of RDW and mortality in unadjusted
      analysis (OR 1.32; 95%CI 1.27-1.39, p<0.001). RDW was strongly correlated with
      different pathways including inflammation (coefficient of determination (R2)
      0.30; p<0.001), nutrition (R2 0.20; p<0.001) and blood diseases (R2 0.30; p<0.001
      The association was eliminated after including different biological pathways into
      the models with the fully adjusted regression model showing an OR of 1.02 (95%CI
      0.93-1.12; p = 0.664) for the association of RDW and mortality. Similar effects
      were found for other outcomes including intensive care unit admission and
      hospital readmission. CONCLUSION: Our data suggests that RDW is a strong
      surrogate marker of mortality in unselected medical inpatients with most of the
      prognostic information being explained by other disease factors. The strong
      correlation of RDW and different biological pathways such as chronic
      inflammation, malnutrition and blood disease suggest that RDW may be viewed as an
      unspecific and general "chronic disease prognostic marker".

PMID- 29342204
TI  - Bulk metal concentrations versus total suspended solids in rivers: Time-invariant
      & catchment-specific relationships.
AB  - Suspended particles in rivers can act as carriers of potentially bioavailable
      metal species and are thus an emerging area of interest in river system
      monitoring. The delineation of bulk metals concentrations in river water into
      dissolved and particulate components is also important for risk assessment.
      Linear relationships between bulk metal concentrations in water (CW,tot) and
      total suspended solids (TSS) in water can be used to easily evaluate dissolved
      (CW, intercept) and particle-bound metal fluxes (CSUS, slope) in streams (CW,tot
      = CW + CSUS TSS). In this study, we apply this principle to catchments in Iran
      (Haraz) and Germany (Ammer, Goldersbach, and Steinlach) that show differences in
      geology, geochemistry, land use and hydrological characteristics. For each
      catchment, particle-bound and dissolved concentrations for a suite of metals in
      water were calculated based on linear regressions of total suspended solids and
      total metal concentrations. Results were replicable across sampling campaigns in
      different years and seasons (between 2013 and 2016) and could be reproduced in a
      laboratory sedimentation experiment. CSUS values generally showed little
      variability in different catchments and agree well with soil background values
      for some metals (e.g. lead and nickel) while other metals (e.g. copper) indicate
      anthropogenic influences. CW was elevated in the Haraz (Iran) catchment,
      indicating higher bioavailability and potential human and ecological health
      concerns (where higher values of CSUS/CW are considered as a risk indicator).

PMID- 29342205
TI  - Correction: Cholecystectomy can increase the risk of colorectal cancer: A meta
      analysis of 10 cohort studies.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0181852.].

PMID- 29342207
TI  - Prognosis of chronic kidney disease with normal-range proteinuria: The CKD-ROUTE
      study.
AB  - BACKGROUND: Although lower estimated glomerular filtration rate (eGFR) and higher
      proteinuria are high risks for mortality and kidney outcomes, the prognosis of
      chronic kidney disease (CKD) in patients with normal-range proteinuria remains
      unclear. METHODS: In this prospective cohort study, 1138 newly visiting stage G2
      G5 CKD patients were stratified into normal-range and abnormal-range proteinuria
      groups. Study endpoints were CKD progression (>50% eGFR loss or initiation of
      dialysis), cardiovascular events, and all-cause death. RESULTS: In total, 927
      patients who were followed for >6 months were included in the analysis. The mean
      age was 67 years, and 70.2% were male. During a median follow-up of 35 months,
      CKD progression, cardiovascular events, and mortality were observed in 223, 110,
      and 55 patients, respectively. Patients with normal-range proteinuria had a
      significantly lower risk for CKD progression (hazard ratio, 0.20; 95% confidence
      interval, 0.10-0.38) than those with abnormal-proteinuria by multivariate Cox
      proportional hazard analysis. We also analyzed patients with normal-range
      proteinuria (n = 351). Nephrosclerosis was the most frequent cause of CKD among
      all patients with normal-range proteinuria (59.7%). During a median follow-up of
      36 months, CKD progression, cardiovascular events, and mortality were observed in
      10, 28, and 18 patients, respectively. The Kaplan-Meyer analysis demonstrated
      that the risks of CKD progression and cardiovascular events were not
      significantly different among CKD stages, whereas the risk of death was
      significantly higher in patients with advanced-stage CKD. Multivariate Cox
      proportional hazard analysis showed that the risk of three endpoints did not
      significantly differ among CKD stages. CONCLUSION: Newly visiting CKD patients
      with normal-range proteinuria, who tend to be overlooked during health checkups
      did not exhibit a decrease in kidney function even in advanced CKD stages under
      specialized nephrology care.

PMID- 29342206
TI  - Silymarin prevents acetaminophen-induced hepatotoxicity in mice.
AB  - Acetaminophen or paracetamol (APAP) overdose is a common cause of liver injury.
      Silymarin (SLM) is a hepatoprotective agent widely used for treating liver injury
      of different origin. In order to evaluate the possible beneficial effects of SLM,
      Balb/c mice were pretreated with SLM (100 mg/kg b.wt. per os) once daily for
      three days. Two hours after the last SLM dose, the mice were administered APAP
      (300 mg/kg b.wt. i.p.) and killed 6 (T6), 12 (T12) and 24 (T24) hours later. SLM
      treated mice exhibited a significant reduction in APAP-induced liver injury,
      assessed according to AST and ALT release and histological examination. SLM
      treatment significantly reduced superoxide production, as indicated by lower GSSG
      content, lower HO-1 induction, alleviated nitrosative stress, decreased p-JNK
      activation and direct measurement of mitochondrial superoxide production in
      vitro. SLM did not affect the APAP-induced decrease in CYP2E1 activity and
      expression during the first 12 hrs. Neutrophil infiltration and enhanced
      expression of inflammatory markers were first detected at T12 in both groups.
      Inflammation progressed in the APAP group at T24 but became attenuated in SLM
      treated animals. Histological examination suggests that necrosis the dominant
      cell death pathway in APAP intoxication, which is partially preventable by SLM
      pretreatment. We demonstrate that SLM significantly protects against APAP-induced
      liver damage through the scavenger activity of SLM and the reduction of
      superoxide and peroxynitrite content. Neutrophil-induced damage is probably
      secondary to necrosis development.

PMID- 29342208
TI  - Comparison of traffic-injury related hospitalisation between bicyclists and
      motorcyclists in Taiwan.
AB  - OBJECTIVES: Bicyclists and motorcyclists contribute substantially to the
      morbidity and mortality rates of road crash casualties. The objective of the
      study was to investigate the crash characteristics of bicyclist and motorcyclist
      casualties presented to hospitals in Taiwan resulting from crashes. METHODS: By
      using linked data from The National Traffic Crash Dataset and the National Health
      Insurance Database between 2003 and 2012, logistic regression models were used to
      examine the determinants of hospitalisation among motorcyclist and bicyclist
      casualties. The examined variables include demographic characteristics, road and
      weather conditions, and vehicle characteristics. RESULTS: A total of 1,998,606
      two-wheelers were enrolled in the study, of whom 216,600 were hospitalised:
      203,623 were motorcyclists and 12,964 were bicyclists. Bicyclists were more
      likely to be hospitalised than motorcyclists were (14.0% vs. 10.7%). The pooled
      logistic regression model shows that bicyclists had higher odds of
      hospitalisation than motorcyclists (adjusted odds ratio [AOR] = 1.11, 95%
      confident interval [CI] = 1.08-1.14). In the motorcyclist and bicyclist models,
      helmet non-use appears to be a determinant of hospitalisation for motorcyclists
      (AOR = 1.14, CI = 1.12-1.16), although insignificant for cyclists (AOR = 1.03, CI
      = 0.94-1.12). Other important determinants of hospitalisation for motorcyclists
      and cyclists include female riders, elderly riders, rural roadways, unlicensed
      riding (for motorcyclists only), curved roadways, defective roadways, alcohol
      consumption (only for motorcyclists), and single-vehicle crashes (for
      motorcyclists only). CONCLUSIONS: The result that bicyclists had an increased
      probability of being hospitalised than motorcyclists is particularly noteworthy,
      because there have recently been much more users of bikesharing systems in
      metropolitan cities where cycle helmets are not provided. We further found that
      helmet non-use was also a risk factor for motorcyclists, but insignificant for
      cyclists, possibly due to lower helmet utilization rates among bicyclists. Our
      findings regarding the increased hospitalisation percentage emphasize the
      importance of helmet use.

PMID- 29342209
TI  - Correction: Harmonizing the pixel size in retrospective computed tomography
      radiomics studies.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0178524.].

PMID- 29342210
TI  - Effects of theory of mind performance training on reducing bullying involvement
      in children and adolescents with high-functioning autism spectrum disorder.
AB  - Bullying involvement is prevalent among children and adolescents with autism
      spectrum disorder (ASD). This study examined the effects of theory of mind
      performance training (ToMPT) on reducing bullying involvement in children and
      adolescents with high-functioning ASD. Children and adolescents with high
      functioning ASD completed ToMPT (n = 26) and social skills training (SST; n = 23)
      programs. Participants in both groups and their mothers rated the pretraining and
      posttraining bullying involvement of participants on the Chinese version of the
      School Bullying Experience Questionnaire. The paired t test was used to evaluate
      changes in bullying victimization and perpetration between the pretraining and
      posttraining assessments. Furthermore, the linear mixed-effect model was used to
      examine the difference in the training effect between the ToMPT and SST groups.
      The paired t test indicated that in the ToMPT group, the severities of both self
      reported (p = .039) and mother-reported (p = .003) bullying victimization
      significantly decreased from the pretraining to posttraining assessments, whereas
      in the SST group, only self-reported bullying victimization significantly
      decreased (p = .027). The linear mixed-effect model indicated that compared with
      the SST program, the ToMPT program significantly reduced the severity of mother
      reported bullying victimization (p = .041). The present study supports the
      effects of ToMPT on reducing mother-reported bullying victimization in children
      and adolescents with high-functioning ASD.

PMID- 29342211
TI  - Correction: A Meta-Analysis of the Association between ESR1 Genetic Variants and
      the Risk of Breast Cancer.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0153314.].

PMID- 29342214
TI  - Correction: Large-Scale Diversity of Slope Fishes: Pattern Inconsistency between
      Multiple Diversity Indices.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0066753.].

PMID- 29342212
TI  - Sequence variation in Plasmodium falciparum merozoite surface protein-2 is
      associated with virulence causing severe and cerebral malaria.
AB  - Parasite virulence, an important factor contributing to the severity of
      Plasmodium falciparum infection, varies among P. falciparum strains. Relatively
      little is known regarding markers of virulence capable of identifying strains
      responsible for severe malaria. We investigated the effects of genetic variations
      in the P.f. merozoite surface protein 2 gene (msp2) on virulence, as it was
      previously postulated as a factor. We analyzed 300 msp2 sequences of single P.
      falciparum clone infection from patients with uncomplicated disease as well as
      those admitted for severe malaria with and without cerebral disease. The
      association of msp2 variations with disease severity was examined. We found that
      the N allele at codon 8 of Block 2 in the FC27-like msp2 gene was significantly
      associated with severe disease without cerebral complications (odds ratio = 2.73,
      P = 0.039), while the K allele at codon 17 of Block 4 in the 3D7-like msp2 gene
      was associated with cerebral malaria (odds ratio = 3.52, P = 0.024). The data
      suggests possible roles for the associated alleles on parasite invasion processes
      and immune-mediated pathogenicity. Multiplicity of infection was found to
      associate with severe disease without cerebral complications, but not cerebral
      malaria. Variations in the msp2-FC27-block 2-8N and 3D7-block 4-17K allele appear
      to be parasite virulence markers, and may be useful in determining the likelihood
      for severe and cerebral malaria. Their interactions with potential host factors
      for severe diseases should also be explored.

PMID- 29342213
TI  - Circulating neutrophil transcriptome may reveal intracranial aneurysm signature.
AB  - BACKGROUND: Unruptured intracranial aneurysms (IAs) are typically asymptomatic
      and undetected except for incidental discovery on imaging. Blood-based diagnostic
      biomarkers could lead to improvements in IA management. This exploratory study
      examined circulating neutrophils to determine whether they carry RNA expression
      signatures of IAs. METHODS: Blood samples were collected from patients receiving
      cerebral angiography. Eleven samples were collected from patients with IAs and 11
      from patients without IAs as controls. Samples from the two groups were paired
      based on demographics and comorbidities. RNA was extracted from isolated
      neutrophils and subjected to next-generation RNA sequencing to obtain
      differential expressions for identification of an IA-associated signature.
      Bioinformatics analyses, including gene set enrichment analysis and Ingenuity
      Pathway Analysis, were used to investigate the biological function of all
      differentially expressed transcripts. RESULTS: Transcriptome profiling identified
      258 differentially expressed transcripts in patients with and without IAs.
      Expression differences were consistent with peripheral neutrophil activation. An
      IA-associated RNA expression signature was identified in 82 transcripts (p<0.05,
      fold-change >=2). This signature was able to separate patients with and without
      IAs on hierarchical clustering. Furthermore, in an independent, unpaired,
      replication cohort of patients with IAs (n = 5) and controls (n = 5), the 82
      transcripts separated 9 of 10 patients into their respective groups. CONCLUSION:
      Preliminary findings show that RNA expression from circulating neutrophils
      carries an IA-associated signature. These findings highlight a potential to use
      predictive biomarkers from peripheral blood samples to identify patients with
      IAs.

PMID- 29342215
TI  - Correction: Seventy Years of Asthma in Italy: Age, Period and Cohort Effects on
      Incidence and Remission of Self-Reported Asthma from 1940 to 2010.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0138570.].

PMID- 29342216
TI  - In Vitro activity of novel glycopolymer against clinical isolates of multidrug
      resistant Staphylococcus aureus.
AB  - The incidence of multidrug-resistant (MDR) organisms, including methicillin
      resistant Staphylococcus aureus (MRSA), is a serious threat to public health.
      Progress in developing new therapeutics is being outpaced by antibiotic
      resistance development, and alternative agents that rapidly permeabilize bacteria
      hold tremendous potential for treating MDR infections. A new class of
      glycopolymers includes polycationic poly-N (acetyl, arginyl) glucosamine (PAAG)
      is under development as an alternative to traditional antibiotic strategies to
      treat MRSA infections. This study demonstrates the antibacterial activity of PAAG
      against clinical isolates of methicillin and mupirocin-resistant Staphylococcus
      aureus. Multidrug-resistant S. aureus was rapidly killed by PAAG, which
      completely eradicated 88% (15/17) of all tested strains (6-log reduction in CFU)
      in <= 12-hours at doses that are non-toxic to mammalian cells. PAAG also
      sensitized all the clinical MRSA strains (17/17) to oxacillin as demonstrated by
      the observed reduction in the oxacillin MIC to below the antibiotic resistance
      breakpoint. The effect of PAAG and standard antibiotics including vancomycin,
      oxacillin, mupirocin and bacitracin on MRSA permeability was studied by measuring
      propidium iodide (PI) uptake by bacterial cells. Antimicrobial resistance studies
      showed that S. aureus developed resistance to PAAG at a rate slower than to
      mupirocin but similar to bacitracin. PAAG was observed to resensitize drug
      resistant S. aureus strains sampled from passage 13 and 20 of the multi-passage
      resistance study, reducing MICs of mupirocin and bacitracin below their clinical
      sensitivity breakpoints. This class of bacterial permeabilizing glycopolymers may
      provide a new tool in the battle against multidrug-resistant bacteria.

PMID- 29342217
TI  - How do the outcomes of the DEKA Arm compare to conventional prostheses?
AB  - OBJECTIVES: Objectives were to 1) compare self-reported function, dexterity,
      activity performance, quality of life and community integration of the DEKA Arm
      to conventional prostheses; and 2) examine differences in outcomes by
      conventional prosthesis type, terminal device type and by DEKA Arm configuration
      level. METHODS: This was a two-part study; Part A consisted of in-laboratory
      training. Part B consisted of home use. Study participants were 23 prosthesis
      users (mean age = 45 +/- 16; 87% male) who completed Part A, and 15 (mean age =
      45 +/- 18; 87% male) who completed Parts A and B. Outcomes including self-report
      and performance measures, were collected at Baseline using participants' personal
      prostheses and at the End of Parts A and B. Scores were compared using paired t
      tests. Wilcoxon signed-rank tests were used to compare outcomes for the full
      sample, and for the sample stratified by device and terminal device type.
      Analysis of outcomes by configuration level was performed graphically. RESULTS:
      At the End of Part A activity performance using the DEKA Arm and conventional
      prosthesis was equivalent, but slower with the DEKA Arm. After Part B,
      performance using the DEKA Arm surpassed conventional prosthesis scores, and
      speed of activity completion was equivalent. Participants reported using the DEKA
      Arm to perform more activities, had less perceived disability, and less
      difficulty in activities at the End of A and B as compared to Baseline. No
      differences were observed in dexterity, prosthetic skill, spontaneity, pain,
      community integration or quality of life. Comparisons stratified by device type
      revealed similar patterns. Graphic comparisons revealed variations by
      configuration level. CONCLUSION: Participants using the DEKA Arm had less
      perceived disability and more engagement of the prosthesis in everyday tasks,
      although activity performance was slower. After home use experience, activity
      performance was improved and activity speed equivalent to using conventional
      prostheses.

PMID- 29342218
TI  - Cross-lagged structural equation models for the relationship between health
      related state and behaviours and body bullying in adolescence: findings from
      longitudinal study ELANA.
AB  - We investigated the stability and the directionality of being body bullied and a
      set of four variables- 1) Body Mass Index (BMI), 2) moderate and vigorous
      physical activity (MVPA), 3) television time (TV) and 4) video game/computer time
      (VG)-, termed in the present study as 'health-related state and behaviours
      (HRSB)'-across adolescence. The Adolescent Nutritional Assessment Longitudinal
      Study (ELANA) is a cohort study conducted among middle school students from two
      public and four private schools in Rio de Janeiro-Brazil. We analysed data from
      2010 (T1) and 2012 (T2) among 810 adolescents (aged 9-15 at T1). Gender-specific
      structural equation models (SEM) were estimated, including autoregressive paths
      for the HRSB and being body bullied over time, correlations at T1 and T2,
      respectively, and cross-lagged effects. The results presented significant
      stability coefficients for almost all variables over time in both genders (except
      for MVPA in boys and girls and TV time among girls). There were positive
      correlations between BMI and being body bullied, as well as between TV and VG for
      boys (0.32, p<0.001 and 0.24, p<0.001, respectively) and girls (0.30, p<0.001 and
      0.30, p<0.001, respectively) at T1. It remained significant at T2 (boys: 0.18,
      p<0.05 and 0.16, p<0.01; girls: 0.21, p<0.01 and 0.22, p<0.01, respectively).
      Examining the cross-lagged paths between being body bullied and HRSB, we observed
      that the reciprocal model provided the best fit for boys, indicating that BMI at
      T1 had a significant effect in being body bullied at T2 (0.12, p<0.05) and being
      body bullied at T1 had an effect on VG at T2 (0.14, p<0.01). Among girls the
      forward causation model showed the best fit, demonstrating a significant effect
      of being body bullied at T1 on VG at T2 (0.16, p<0.01). Apart from MVPA, both
      being body bullying and HRSB were largely stable across adolescence. For boys and
      girls alike, exposure to being body bullied seemed to increase their time spent
      on VG, while for boys BMI also predicted being body bullied. This study
      highlighted the complex interplay between being body bullied and HRSB and the
      importance of acknowledging gender differences in this context.

PMID- 29342220
TI  - Correction: IFNAR2-dependent gene expression profile induced by IFN-alpha in
      Pteropus alecto bat cells and impact of IFNAR2 knockout on virus infection.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0182866.].

PMID- 29342219
TI  - The expression profile and prognostic significance of eukaryotic translation
      elongation factors in different cancers.
AB  - Eukaryotic translation factors, especially initiation factors have garnered much
      attention with regards to their role in the onset and progression of different
      cancers. However, the expression levels and prognostic significance of
      translation elongation factors remain poorly explored in different cancers. In
      this study, we have investigated the mRNA transcript levels of seven translation
      elongation factors in different cancer types using Oncomine and TCGA databases.
      Furthermore, we have identified the prognostic significance of these factors
      using Kaplan-Meier Plotter and SurvExpress databases. We observed altered
      expression levels of all the elongation factors in different cancers. Higher
      expression of EEF1A2, EEF1B2, EEF1G, EEF1D, EEF1E1 and EEF2 was observed in most
      of the cancer types, whereas reverse trend was observed for EEF1A1.
      Overexpression of many factors predicted poor prognosis in breast (EEF1D, EEF1E1,
      EEF2) and lung cancer (EEF1A2, EEF1B2, EEF1G, EEF1E1). However, we didn't see any
      common correlation of expression levels of elongation factors with survival
      outcomes across cancer types. Cancer subtype stratification showed association of
      survival outcomes and expression levels of elongation factors in specific sub
      types of breast, lung and gastric cancer. Most interestingly, we observed a
      reciprocal relationship between the expression levels of the two EEF1A isoforms
      viz. EEF1A1 and EEF1A2, in most of the cancer types. Our results suggest that
      translation elongation factors can have a role in tumorigenesis and affect
      survival in cancer specific manner. Elongation factors have potential to serve as
      biomarkers and therapeutic drug targets, yet further study is required.
      Reciprocal relationship of differential expression between EEF1A isoforms
      observed in multiple cancer types indicates opposing roles in cancer and needs
      further investigation.

PMID- 29342221
TI  - Genotype-by-environment interactions affecting heterosis in maize.
AB  - The environment can influence heterosis, the phenomena in which the offspring of
      two inbred parents exhibits phenotypic performance beyond the inbred parents for
      specific traits. In this study we measured 25 traits in a set of 47 maize hybrids
      and their inbred parents grown in 16 different environments with varying levels
      of average productivity. By quantifying 25 vegetative and reproductive traits
      across the life cycle we were able to analyze interactions between the
      environment and multiple distinct instances of heterosis. The magnitude and rank
      among hybrids for better-parent heterosis (BPH) varied for the different traits
      and environments. Across the traits, a higher within plot variance was observed
      for inbred lines compared to hybrids. However, for most traits, variance across
      environments was not significantly different for inbred lines compared to
      hybrids. Further, for many traits the correlations of BPH to hybrid performance
      and BPH to better parent performance were of comparable magnitude. These results
      indicate that inbred lines and hybrids show similar trends in environmental
      response and both are contributing to observed genotype-by-environment
      interactions for heterosis. This study highlights the degree of heterosis is not
      an inherent trait of a specific hybrid, but varies depending on the trait
      measured and the environment where that trait is measured. Studies that attempt
      to correlate molecular processes with heterosis are hindered by the fact that
      heterosis is not a consistent attribute of a specific hybrid.

PMID- 29342223
TI  - Development of a Job Exposure Matrix for Noise in the Swedish Soft Tissue Paper
      Industry.
AB  - Objectives: Noise exposure is a common occupational hazard, but has not been
      sufficiently characterized in paper mills. We developed a job-exposure matrix
      (JEM) for noise exposure for use in estimating exposures among Swedish soft
      tissue paper mill workers. Methods: We used a combination of area and personal
      dosimetry noise exposure measurements made at four soft tissue paper mills by
      industry and research staff between 1977 and 2013 to estimate noise exposures by
      department, location, and job title. We then utilized these estimates, in
      conjunction with information on process and facility changes and use of hearing
      protection collected via focus groups, to create a seven-category, semi
      quantitative JEM for all departments, locations, and job titles spanning the
      years 1940-2010. Results: The results of the 1157 area and personal dosimetry
      noise measurements indicated that noise levels have generally declined in Swedish
      paper mills over time, though these changes have been neither uniform nor
      monotonic within or across the four mills. Focus group results indicated that use
      of hearing protection has generally increased over time. The noise JEM totals
      1917 cells, with each cell representing a unique combination of operation, job
      title, and single year. We estimated that ~50% of workers at the four mills
      assessed were exposed at or above the Swedish 8-h average noise exposure limit of
      an 85 dBA at the conclusion of the study period in 2010. Conclusions: Our results
      highlight the continuing need for hearing loss prevention and noise control
      efforts at these and similar mills, and the completed JEM now represents a tool
      for use in epidemiological studies of noise-related health outcomes.

PMID- 29342222
TI  - Mechano-electric feedback effects in a three-dimensional (3D) model of the
      contracting cardiac ventricle.
AB  - Mechano-electric feedback affects the electrophysiological and mechanical
      function of the heart and the cellular, tissue, and organ properties. To
      determine the main factors that contribute to this effect, this study
      investigated the changes in the action potential characteristics of the ventricle
      during contraction. A model of stretch-activated channels was incorporated into a
      three-dimensional multiscale model of the contracting ventricle to assess the
      effect of different preload lengths on the electrophysiological behavior. The
      model describes the initiation and propagation of the electrical impulse, as well
      as the passive (stretch) and active (contraction) changes in the cardiac
      mechanics. Simulations were performed to quantify the relationship between the
      cellular activation and recovery patterns as well as the action potential
      durations at different preload lengths in normal and heart failure pathological
      conditions. The simulation results showed that heart failure significantly
      affected the excitation propagation parameters compared to normal condition. The
      results showed that the mechano-electrical feedback effects appear to be most
      important in failing hearts with low ejection fraction.

PMID- 29342224
TI  - Elabela-APJ axis contributes to embryonic development and prevents pre-eclampsia
      in pregnancy.

PMID- 29342225
TI  - RE: "DIETARY INTAKE OF ANTIOXIDANT VITAMINS AND CAROTENOIDS AND RISK OF
      DEVELOPING ACTIVE TUBERCULOSIS IN A PROSPECTIVE POPULATION-BASED COHORT".

PMID- 29342226
TI  - Don't Judge a Book by its Cover: Examiner Expectancy Effects Predict
      Neuropsychological Performance for Individuals Judged as Chronic Cannabis Users.
AB  - Objective: The experimenter expectancy effect confound remains largely unexplored
      in neuropsychological research and has never been investigated among cannabis
      users. This study investigated whether examiner expectancies of cannabis user
      status affected examinees' neuropsychological performance. Method: Participants
      included 41 cannabis users and 20 non-users. Before testing, examiners who were
      blind to participant user status privately rated whether they believed the
      examinee was a cannabis user or non-user. Examiners then administered a battery
      of neuropsychological and performance validity measures. Multiple regression
      analyses compared performance between examinees judged as cannabis users (n = 37)
      and those judged as non-users (n = 24). Results: Examiners' judgments of cannabis
      users were 75% accurate; judgments of non-users were at chance. After controlling
      for age, gender, and actual user status, examiner judgments of cannabis user
      status predicted performance on two measures (California Verbal Learning Test-II,
      and Trail Making Test B; p < .05), as individuals judged as cannabis users
      obtained lower scores than those judged as non-users. Conclusions: Examiners'
      judgments of cannabis user status predicted performance even after controlling
      for actual user status, indicating vulnerability to examiner expectancy effects.
      These findings have important implications for both research and clinical
      settings, as scores may partially reflect examiners' expectations regarding
      cannabis effects rather than participants' cognitive abilities. These results
      demonstrate the need for expectancy effect research in the neuropsychological
      assessment of all populations, not just cannabis users.

PMID- 29342227
TI  - Brain Cytosolic Phospholipase A2alpha Mediates Angiotensin II-Induced
      Hypertension and Reactive Oxygen Species Production in Male Mice.
AB  - BACKGROUND: Recently, we reported that angiotensin II (Ang II)-induced
      hypertension is mediated by group IV cytosolic phospholipase A2alpha (cPLA2alpha)
      via production of prohypertensive eicosanoids. Since Ang II increases blood
      pressure (BP) via its action in the subfornical organ (SFO), it led us to
      investigate the expression and possible contribution of cPLA2alpha to oxidative
      stress and development of hypertension in this brain area. METHODS: Adenovirus
      (Ad)-green fluorescence protein (GFP) cPLA2alpha short hairpin (sh) RNA (Ad
      cPLA2alpha shRNA) and its control Ad-scrambled shRNA (Ad-Scr shRNA) or Ad
      enhanced cyan fluorescence protein cPLA2alpha DNA (Ad-cPLA2alpha DNA) and its
      control Ad-GFP DNA were transduced into SFO of cPLA2alpha+/+ and cPLA2alpha-/-
      male mice, respectively. Ang II (700 ng/kg/min) was infused for 14 days in these
      mice, and BP was measured by tail-cuff and radio telemetry. cPLA2 activity,
      reactive oxygen species production, and endoplasmic reticulum stress were
      measured in the SFO. RESULTS: Transduction of SFO with Ad-cPLA2alpha shRNA, but
      not Ad-Scr shRNA in cPLA2alpha+/+ mice, minimized expression of cPLA2alpha, Ang
      II-induced cPLA2alpha activity and oxidative stress in the SFO, BP, and cardiac
      and renal fibrosis. In contrast, Ad-cPLA2alpha DNA, but not its control Ad-GFP
      DNA in cPLA2alpha-/- mice, restored the expression of cPLA2alpha, and Ang II
      induced increase in cPLA2 activity and oxidative stress in the SFO, BP, cardiac,
      and renal fibrosis. CONCLUSIONS: These data suggest that cPLA2alpha in the SFO is
      crucial in mediating Ang II-induced hypertension and associated pathogenesis.
      Therefore, development of selective cPLA2alpha inhibitors could be useful in
      treating hypertension and its pathogenesis.

PMID- 29342228
TI  - Labiaplasty: Indications and Predictors of Postoperative Sequelae in 451
      Consecutive Cases.
AB  - Background: The increasing demand for labiaplasty is well recognized; however,
      the procedure remains contentious. Objectives: We aim to provide a large-scale,
      up-to-date analysis of labiaplasty outcomes and factors influencing postoperative
      sequelae (POS). Methods: We analyzed a single-center, prospectively maintained
      database of females undergoing labiaplasty between 2002 and 2017. Demographic,
      procedural, and outcomes' data were retrieved. Binary logistic regressions were
      used to evaluate the odds of developing POS (revisional surgery and
      complications); presented as odds ratios (OR) with 95% confidence intervals (CI).
      Results: Data for 451 consecutive patients were retrieved, ten of whom were <18
      years of age. Overall, 86% were Caucasian, mean age was 32.6 years, and 11.8%
      were smokers. Concomitant labia majora reduction was performed in 7.3%, and
      clitoral hood reduction in 5.8%. There were 32 cases of POS (7.1%), while the
      complication rate was 3.8%. Comparing those with POS to those without, there were
      no differences in age (32.8 vs 29.9 years, P = 0.210), operative time (78.5 vs
      80.6 minutes, P = 0.246), or comorbidities (P > 0.05 for all). On univariable
      analysis, increased odds of POS occurred with sexual dysfunction as an indication
      for surgery (OR 3.778, CI 1.682-8.483). On subgroup analysis of those >=18 years,
      both smoking (2.576, CI 1.044-6.357) and sexual dysfunction as an indication (OR
      4.022, CI 1.772-9.131) increased the odds of POS. On multivariable analysis of
      the subgroup, sexual dysfunction as an indication persisted in significance (OR
      3.850, CI 1.683-8.807). Conclusions: Results compare favorably with previously
      reported complication and revisional surgery rates. Smoking and sexual
      dysfunction may increase the risk of complications. Level of Evidence 2: 

PMID- 29342229
TI  - A rapid epistatic mixed-model association analysis by linear retransformations of
      genomic estimated values.
AB  - Motivation: Epistasis provides a feasible way for probing potential genetic
      mechanism of complex traits. However, time-consuming computation challenges
      successful detection of interaction in practice, especially when linear mixed
      model (LMM) is used to control type I error in the presence of population
      structure and cryptic relatedness. Results: A rapid epistatic mixed-model
      association analysis (REMMA) method was developed to overcome computational
      limitation. This method first estimates individuals' epistatic effects by an
      extended genomic best linear unbiased prediction (EG-BLUP) model with additive
      and epistatic kinship matrix, then pairwise interaction effects are obtained by
      linear retransformations of individuals' epistatic effects. Simulation studies
      showed that REMMA could control type I error and increase statistical power in
      detecting epistatic QTNs in comparison with existing LMM-based FaST-LMM. We
      applied REMMA to two real datasets, a mouse dataset and the Wellcome Trust Case
      Control Consortium (WTCCC) data. Application to the mouse data further confirmed
      the performance of REMMA in controlling type I error. For the WTCCC data, we
      found most epistatic QTNs for type 1 diabetes (T1D) located in a major
      histocompatibility complex (MHC) region, from which a large interacting network
      with 12 hub genes (interacting with ten or more genes) was established.
      Availability and implementation: Our REMMA method can be freely accessed at
      https://github.com/chaoning/REMMA. Contact: liujf@cau.edu.cn. Supplementary
      information: Supplementary data are available at Bioinformatics online.

PMID- 29342230
TI  - Metformin as an anti-cancer agent: actions and mechanisms targeting cancer stem
      cells.
AB  - Metformin, a first line medication for type II diabetes, initially entered the
      spotlight as a promising anti-cancer agent due to epidemiologic reports that
      found reduced cancer risk and improved clinical outcomes in diabetic patients
      taking metformin. To uncover the anti-cancer mechanisms of metformin, preclinical
      studies determined that metformin impairs cellular metabolism and suppresses
      oncogenic signaling pathways, including receptor tyrosine kinase, PI3K/Akt, and
      mTOR pathways. Recently, the anti-cancer potential of metformin has gained
      increasing interest due to its inhibitory effects on cancer stem cells (CSCs),
      which are associated with tumor metastasis, drug resistance, and relapse. Studies
      using various cancer models, including breast, pancreatic, prostate, and colon,
      have demonstrated the potency of metformin in attenuating CSCs through the
      targeting of specific pathways involved in cell differentiation, renewal,
      metastasis, and metabolism. In this review, we provide a comprehensive overview
      of the anti-cancer actions and mechanisms of metformin, including the regulation
      of CSCs and related pathways. We also discuss the potential anti-cancer
      applications of metformin as mono- or combination therapies.

PMID- 29342232
TI  - Informational and linguistic analysis of large genomic sequence collections via
      efficient Hadoop cluster algorithms.
AB  - Motivation: Information theoretic and compositional/linguistic analysis of
      genomes have a central role in bioinformatics, even more so since the associated
      methodologies are becoming very valuable also for epigenomic and meta-genomic
      studies. The kernel of those methods is based on the collection of k-mer
      statistics, i.e. how many times each k-mer in {A,C,G,T}k occurs in a DNA
      sequence. Although this problem is computationally very simple and efficiently
      solvable on a conventional computer, the sheer amount of data available now in
      applications demands to resort to parallel and distributed computing. Indeed,
      those type of algorithms have been developed to collect k-mer statistics in the
      realm of genome assembly. However, they are so specialized to this domain that
      they do not extend easily to the computation of informational and linguistic
      indices, concurrently on sets of genomes. Results: Following the well-established
      approach in many disciplines, and with a growing success also in bioinformatics,
      to resort to MapReduce and Hadoop to deal with 'Big Data' problems, we present
      KCH, the first set of MapReduce algorithms able to perform concurrently
      informational and linguistic analysis of large collections of genomic sequences
      on a Hadoop cluster. The benchmarking of KCH that we provide indicates that it is
      quite effective and versatile. It is also competitive with respect to the
      parallel and distributed algorithms highly specialized to k-mer statistics
      collection for genome assembly problems. In conclusion, KCH is a much needed
      addition to the growing number of algorithms and tools that use MapReduce for
      bioinformatics core applications. Availability and implementation: The software,
      including instructions for running it over Amazon AWS, as well as the datasets
      are available at http://www.di-srv.unisa.it/KCH. Contact:
      umberto.ferraro@uniroma1.it. Supplementary information: Supplementary data are
      available at Bioinformatics online.

PMID- 29342231
TI  - Mapping gene regulatory networks from single-cell omics data.
AB  - Single-cell techniques are advancing rapidly and are yielding unprecedented
      insight into cellular heterogeneity. Mapping the gene regulatory networks (GRNs)
      underlying cell states provides attractive opportunities to mechanistically
      understand this heterogeneity. In this review, we discuss recently emerging
      methods to map GRNs from single-cell transcriptomics data, tackling the challenge
      of increased noise levels and data sparsity compared with bulk data, alongside
      increasing data volumes. Next, we discuss how new techniques for single-cell
      epigenomics, such as single-cell ATAC-seq and single-cell DNA methylation
      profiling, can be used to decipher gene regulatory programmes. We finally look
      forward to the application of single-cell multi-omics and perturbation techniques
      that will likely play important roles for GRN inference in the future.

PMID- 29342234
TI  - Stability-Indicating HPLC and HPTLC Methods for Determination of Agomelatine and
      its Degradation Products.
AB  - Two accurate, sensitive and highly selective stability-indicating methods are
      developed and validated for simultaneous determination of Agomelatine (AGM) and
      its forced degradation products (Deg I and II). The first method is High
      Performance Liquid Chromatography for separation and quantitation of AGM, Deg I
      and II on a C18 column (250 mm * 4.6 mm, 5 MUm p.s) in isocratic mode by using a
      binary mixture of Potassium dihydrogen phosphate (0.05 M, pH adjusted to 2.9 with
      orthophosphoric acid): acetonitrile (60:40, v/v) at a flow rate of 2 mL/min. The
      components were detected at 230 nm over a concentration range of 0.5-10 MUg/mL
      for AGM and 0.5-5 MUg/mL for both Deg I and II. The second method is High
      Performance Thin-Layer Chromatography, where AGM, Deg I and II were separated on
      silica gel HPTLC F254 plates using chloroform:methanol:ammonia solution (9:1:0.1,
      by volume) as a developing system. The separated bands were scanned at 230 nm
      over the concentration range of 0.2-1.2 MUg/band for AGM in pure form and human
      plasma and 0.1-1 MUg/band for both Deg I and II. The proposed methods were
      successfully applied for analysis of AGM in pharmaceutical formulations. The
      results obtained by the proposed methods were statistically compared to the
      reported HPLC method revealing high accuracy and good precision.

PMID- 29342233
TI  - QuantumClone: clonal assessment of functional mutations in cancer based on a
      genotype-aware method for clonal reconstruction.
AB  - Motivation: In cancer, clonal evolution is assessed based on information coming
      from single nucleotide variants and copy number alterations. Nonetheless,
      existing methods often fail to accurately combine information from both sources
      to truthfully reconstruct clonal populations in a given tumor sample or in a set
      of tumor samples coming from the same patient. Moreover, previously published
      methods detect clones from a single set of variants. As a result, compromises
      have to be done between stringent variant filtering [reducing dispersion in
      variant allele frequency estimates (VAFs)] and using all biologically relevant
      variants. Results: We present a framework for defining cancer clones using most
      reliable variants of high depth of coverage and assigning functional mutations to
      the detected clones. The key element of our framework is QuantumClone, a method
      for variant clustering into clones based on VAFs, genotypes of corresponding
      regions and information about tumor purity. We validated QuantumClone and our
      framework on simulated data. We then applied our framework to whole genome
      sequencing data for 19 neuroblastoma trios each including constitutional,
      diagnosis and relapse samples. We confirmed an enrichment of damaging variants
      within such pathways as MAPK (mitogen-activated protein kinases), neuritogenesis,
      epithelial-mesenchymal transition, cell survival and DNA repair. Most pathways
      had more damaging variants in the expanding clones compared to shrinking ones,
      which can be explained by the increased total number of variants between these
      two populations. Functional mutational rate varied for ancestral clones and
      clones shrinking or expanding upon treatment, suggesting changes in clone
      selection mechanisms at different time points of tumor evolution. Availability
      and implementation: Source code and binaries of the QuantumClone R package are
      freely available for download at https://CRAN.R-project.org/package=QuantumClone.
      Contact: gudrun.schleiermacher@curie.fr or valentina.boeva@inserm.fr.
      Supplementary information: Supplementary data are available at Bioinformatics
      online.

PMID- 29342235
TI  - Estimation of Lead Exposure Prevalence in Korean Population through Combining
      Multiple Experts' Judgment based on Objective Data Sources.
AB  - Objective: Estimating carcinogen exposure prevalence is important for preventing
      occupational cancers. To develop the Korean version of CARcinogen EXposure
      (CAREX), a carcinogen surveillance system used in many countries, we estimated
      lead exposure prevalence in the Korean working population. Methods: We used three
      Korean nationwide data sources to obtain objective database-derived prevalences
      of lead exposure across industries: airborne lead measurement data from the work
      environment measurement database (WEMD), blood lead measurement data from the
      special health examination database (SHED), and lead exposure prevalence computed
      using data from the work environment condition survey (WECS), which is a
      nationwide occupational exposure survey. We also asked a panel of 52 experts with
      >=20 years of experience in industrial hygiene practice for their judgment about
      lead exposure prevalence across industries after they reviewed the database
      derived prevalences computed from the three exposure databases. We developed and
      compared various estimation methods for combining the experts' judgments. The
      2010 census was used as the reference population to estimate the number of lead
      exposed workers in 228 industries by multiplying the exposure prevalence by the
      number of workers in each industry. Results: The database-derived prevalences of
      lead exposure in the 228 industries were calculated using data collected between
      2009 and 2011 from the WEMD and SHED and from the 2009 WECS. From the various
      estimation methods assessed, the median values of experts' responses were
      selected as our estimates of lead exposure prevalence in each industry. As a
      result, it was estimated that 129,250 Korean workers were exposed to lead in
      2010. Conclusions: Based on objective databases, we developed a method for
      estimating exposure prevalence for the CAREX system by combining experts'
      judgments. This work may offer an unbiased approach to the development process
      that accounts for the uncertainty in exposure.

PMID- 29342236
TI  - MAGNAMWAR: an R package for genome-wide association studies of bacterial
      orthologs.
AB  - Summary: Here we report on an R package for genome-wide association studies of
      orthologous genes in bacteria. Before using the software, orthologs from
      bacterial genomes or metagenomes are defined using local or online
      implementations of OrthoMCL. These presence-absence patterns are statistically
      associated with variation in user-collected phenotypes using the Mono-Associated
      GNotobiotic Animals Metagenome-Wide Association R package (MAGNAMWAR). Genotype
      phenotype associations can be performed with several different statistical tests
      based on the type and distribution of the data. Availability and implementation:
      MAGNAMWAR is available on CRAN. Contact: john_chaston@byu.edu.

PMID- 29342237
TI  - The Roles of Subdivisions of Human Insula in Emotion Perception and Auditory
      Processing.
AB  - Previous studies have shown insular activations involving sensory, motor, and
      affective processing. However, the functional roles of subdivisions within the
      human insula are still not well understood. In the present study, we used
      intracranial electroencephalography and electrical cortical stimulation to
      investigate the causal roles of subdivisions of the insula in auditory emotion
      perception in epilepsy patients implanted with depth electrodes in this brain
      region. The posterior and the anterior subdivisions of the human insula,
      identified based on structural and functional analyses, showed distinct response
      properties to auditory emotional stimuli. The posterior insula showed auditory
      responses that resemble those observed in Heschl's gyrus, whereas the anterior
      insula (AI) responded to the emotional contents of the auditory stimuli in a
      similar way as observed in the amygdala. Furthermore, the degree of the
      differentiation between various emotion types increased from the posterior to the
      AI. Our findings suggest different roles played by the two regions of the human
      insula and a transformation from sensory to affective representations in auditory
      modality along the posterior-to-anterior axis in the human insula.

PMID- 29342238
TI  - Rhythmic Spontaneous Activity Mediates the Age-Related Decline in Somatosensory
      Function.
AB  - Sensory gating is a neurophysiological process whereby the response to a second
      stimulus in a pair of identical stimuli is attenuated, and it is thought to
      reflect the capacity of the CNS to preserve neural resources for behaviorally
      relevant stimuli. Such gating is observed across multiple sensory modalities and
      is modulated by age, but the mechanisms involved are not understood. In this
      study, we examined somatosensory gating in 68 healthy adults using
      magnetoencephalography (MEG) and advanced oscillatory and time-domain analysis
      methods. MEG data underwent source reconstruction and peak voxel time series data
      were extracted to evaluate the dynamics of somatosensory gating, and the impact
      of spontaneous neural activity immediately preceding the stimulation. We found
      that gating declined with increasing age and that older adults had significantly
      reduced gating relative to younger adults, suggesting impaired local inhibitory
      function. Most importantly, older adults had significantly elevated spontaneous
      activity preceding the stimulation, and this effect fully mediated the impact of
      aging on sensory gating. In conclusion, gating in the somatosensory system
      declines with advancing age and this effect is directly tied to increased
      spontaneous neural activity in the primary somatosensory cortices, which is
      likely secondary to age-related declines in local GABA inhibitory function.

PMID- 29342239
TI  - HPLC Estimation, Ex vivo Everted Sac Permeability and In Vivo Pharmacokinetic
      Studies of Darunavir.
AB  - Darunavir ethanolate (DRV) is an efficient protease inhibitor (PI) used in the
      treatment of human immunodeficiency virus (HIV) type-1 patients. An isocratic
      reversed-phase HPLC method was developed to monitor concentration of darunavir in
      in vitro intestinal fluid samples in everted sac absorption model in the presence
      of bioenhancers, viz., piperine, quercetin, naringenin. The method was validated
      and successfully applied to everted sac and pharmacokinetic studies in rats. The
      absorption profiles of DRV and apparent permeability coefficients were
      determined. The proposed method was found to be simple, rapid, robust and
      selective and was applied for continuous ex vivo monitoring of DRV in everted sac
      absorption studies. Of the three bioenhancers screened at different
      concentrations, piperine caused highest and significant 1.5-fold increase in
      apparent permeability of DRV across everted sac tissue. Further, co
      administration of piperine significantly increased the maximum plasma
      concentration of DRV by 1.18-fold confirming the enhancement in its absorption.

PMID- 29342240
TI  - Presence of Myocardial Damage Predicts Future Development of Hypertension in a
      Normotensive Japanese General Population: The Yamagata (Takahata) Study.
AB  - BACKGROUND: A modest rise in blood pressure (BP) reportedly increases
      cardiovascular mortality despite not reaching obvious hypertension, suggesting
      that target organ damages are latently induced by slight BP rising. The goal of
      this study was to determine whether presence of subclinical myocardial damage can
      predict the future development of hypertension in the normotensive general
      population. METHODS AND RESULTS: The cohort study was conducted with subjects who
      participated in a community-based annual health check. Normotensive subjects
      without prior cardiovascular diseases at baseline were eligible for analyses (n =
      524, mean age 58 +/- 9 years; 53% women). We measured heart-type fatty acid
      binding protein (H-FABP) at baseline as a biomarker of ongoing myocardial damage.
      Longitudinal changes in BP were examined during median follow-up period of 6.2
      years, and we investigated the association between the baseline H-FABP level and
      longitudinal BP changes. RESULTS: During the follow-up, 177 subjects (34%)
      developed hypertension. In multivariate Cox proportional hazard analysis adjusted
      for potential confounders including age and baseline BP, presence of myocardial
      damage was significantly associated with the development of hypertension (hazard
      ratio 1.80, 95% confidence interval, 1.26-2.54; P = 0.0014). Furthermore,
      relative risk of myocardial damage for incident hypertension was higher in
      younger subjects and lower BP category. CONCLUSIONS: Presence of subclinical
      myocardial damage was independently associated with the future development of
      hypertension in the normotensive general population.

PMID- 29342241
TI  - iPat: intelligent prediction and association tool for genomic research.
AB  - Summary: The ultimate goal of genomic research is to effectively predict
      phenotypes from genotypes so that medical management can improve human health and
      molecular breeding can increase agricultural production. Genomic prediction or
      selection (GS) plays a complementary role to genome-wide association studies
      (GWAS), which is the primary method to identify genes underlying phenotypes.
      Unfortunately, most computing tools cannot perform data analyses for both GWAS
      and GS. Furthermore, the majority of these tools are executed through a command
      line interface (CLI), which requires programming skills. Non-programmers struggle
      to use them efficiently because of the steep learning curves and zero tolerance
      for data formats and mistakes when inputting keywords and parameters. To address
      these problems, this study developed a software package, named the Intelligent
      Prediction and Association Tool (iPat), with a user-friendly graphical user
      interface. With iPat, GWAS or GS can be performed using a pointing device to
      simply drag and/or click on graphical elements to specify input data files,
      choose input parameters and select analytical models. Models available to users
      include those implemented in third party CLI packages such as GAPIT, PLINK,
      FarmCPU, BLINK, rrBLUP and BGLR. Users can choose any data format and conduct
      analyses with any of these packages. File conversions are automatically conducted
      for specified input data and selected packages. A GWAS-assisted genomic
      prediction method was implemented to perform genomic prediction using any GWAS
      method such as FarmCPU. iPat was written in Java for adaptation to multiple
      operating systems including Windows, Mac and Linux. Availability and
      implementation: The iPat executable file, user manual, tutorials and example
      datasets are freely available at http://zzlab.net/iPat. Contact:
      zhiwu.zhang@wsu.edu.

PMID- 29342242
TI  - Meiotic spindle formation in mammalian oocytes: implications for human
      infertility.
AB  - In the final stage of oogenesis, mammalian oocytes generate a meiotic spindle and
      undergo chromosome segregation to yield an egg that is ready for fertilization.
      Herein, we describe the recent advances in understanding the mechanisms
      controlling formation of the meiotic spindle in metaphase I (MI) and metaphase II
      (MII) in mammalian oocytes, and focus on the differences between mouse and human
      oocytes. Unlike mitotic cells, mammalian oocytes lack typical centrosomes that
      consist of two centrioles and the surrounding pericentriolar matrix proteins,
      which serve as microtubule-organizing centers (MTOCs) in most somatic cells.
      Instead, oocytes rely on different mechanisms for the formation of microtubules
      in MI spindles. Two different mechanisms have been described for MI spindle
      formation in mammalian oocytes. Chromosome-mediated microtubule formation,
      including RAN-mediated spindle formation and chromosomal passenger complex
      mediated spindle elongation, controls the growth of microtubules from chromatin,
      while acentriolar MTOC-mediated microtubule formation contributes to spindle
      formation. Mouse oocytes utilize both chromatin- and MTOC-mediated pathways for
      microtubule formation. The existence of both pathways may provide a fail-safe
      mechanism to ensure high fidelity of chromosome segregation during meiosis.
      Unlike mouse oocytes, human oocytes considered unsuitable for clinical in vitro
      fertilization procedures, lack MTOCs; this may explain why meiosis in human
      oocytes is often error-prone. Understanding the mechanisms of MI/MII spindle
      formation, spindle assembly checkpoint, and chromosome segregation, in mammalian
      oocytes, will provide valuable insights into the molecular mechanisms of human
      infertility.

PMID- 29342243
TI  - Devices in heart failure; diagnosis, detection and disease modification.
AB  - Introduction/background: Implantable cardiac devices are widely used in chronic
      heart failure (CHF) therapy. This review covers current CHF treatment with
      electronic cardiac devices, areas of discussion and emerging technologies.
      Sources of data: A comprehensive search of available literature resources
      including Pubmed, MEDLINE and EMBASE was performed. National and international
      guidelines were accessed. Areas of agreement: Excessive right ventricular pacing
      is detrimental to cardiac function. Cardiac resynchronization therapy is
      beneficial in specific individuals with CHF. Areas of controversy: Implantable
      cardioverter defibrillators might not benefit all. Optimizing CRT delivery.
      Remote monitoring seems not to be of benefit in CHF. Growing points: Device-based
      optimization. Areas timely for developing research: Personalization of device
      therapy. Focussing implantable cardioverter defibrillator therapy. What to do at
      implantable cardioverter defibrillator box change?

PMID- 29342244
TI  - Gli2 Rescues Delays in Brain Development Induced by Kif3a Dysfunction.
AB  - The primary cilium in neural stem cells plays distinct roles in different stages
      during cortical development. Ciliary dysfunctions in human (i.e., ciliopathy)
      cause developmental defects in multiple organs, including brain developmental
      delays, which lead to intellectual disabilities and cognitive deficits. However,
      effective treatment to this devastating developmental disorder is still lacking.
      Here, we first investigated the effects of ciliopathy on neural stem cells by
      knocking down Kif3a, a kinesin II motor required for ciliogenesis, in the
      neurogenic stage of cortical development by in utero electroporation of mouse
      embryos. Brains electroporated with Kif3a shRNA showed defects in neuronal
      migration and differentiation, delays in neural stem cell cycle progression, and
      failures in interkinetic nuclear migration. Interestingly, introduction of Gli1
      and Gli2 both can restore the cell cycle progression by elevating cyclin D1 in
      neural stem cells. Remarkably, enforced Gli2 expression, but not Gli1, partially
      restored the ability of Kif3a-knockdown neurons to differentiate and move from
      the germinal ventricular zone to the cortical plate. Moreover, Cyclin D1
      knockdown abolished Gli2's rescue effect. These findings suggest Gli2 may rescue
      neural stem cell proliferation, differentiation and migration through Cyclin D1
      pathway and may serve as a potential therapeutic target for human ciliopathy
      syndromes through modulating the progression of neural stem cell cycle.

PMID- 29342245
TI  - Structure-Function Relationships of Olfactory and Taste Receptors.
AB  - The field of chemical senses has made major progress in understanding the
      cellular mechanisms of olfaction and taste in the past 2 decades. However, the
      molecular understanding of odor and taste recognition is still lagging far behind
      and will require solving multiple structures of the relevant full-length
      receptors in complex with native ligands to achieve this goal. However, the
      development of multiple complimentary strategies for the structure determination
      of G protein-coupled receptors (GPCRs) makes this goal realistic. The common
      conundrum of how multi-specific receptors that recognize a large number of
      different ligands results in a sensory perception in the brain will only be fully
      understood by a combination of high-resolution receptor structures and functional
      studies. This review discusses the first steps on this pathway, including
      biochemical and physiological assays, forward genetics approaches, molecular
      modeling, and the first steps towards the structural biology of olfactory and
      taste receptors.

PMID- 29342246
TI  - Associations of Quadriceps Torque Properties with Muscle Size, Attenuation, and
      Intramuscular Adipose Tissue in Older Adults.
AB  - Background: Atrophy and fatty infiltration of muscle with aging are associated
      with fractures and falls, however, their direct associations with muscle function
      are not well described. It was hypothesized that participants with lower
      quadriceps muscle attenuation, area, and greater intramuscular adipose tissue
      (IMAT) will exhibit slower rates of torque development (RTD) and lower peak knee
      extension torques. Methods: Data from 4,842 participants (2,041 men, 2,801 women)
      from the Age Gene/Environment Susceptibility Reykjavik Study (mean age 76 +/- 0.1
      years) with complete thigh computed tomography and isometric knee testing.
      Regression models were adjusted for health, behavior, and comorbidities. Muscle
      attenuation was further adjusted for muscle area and IMAT; muscle area adjusted
      for IMAT and attenuation; and IMAT adjusted for muscle area and attenuation.
      Standardized betas (beta) indicate association effect sizes. Results: In the
      fully-adjusted models, attenuation (men beta = 0.06, 95% CI: 0.01, 0.11; women
      beta = 0.07, 95% CI: 0.03, 0.11) and muscle area (men beta = 0.13, 95% CI: 0.07,
      0.19; women beta = 0.10, 95% CI: 0.06, 0.15) were associated with knee RTD.
      Attenuation (men beta = 0.12, 95% CI: 0.08, 0.16; women beta = 0.12, 95% CI:
      0.09, 0.16) and muscle area (men beta = 0.38, 95% CI: 0.33, 0.43; women beta =
      0.33, 95% CI: 0.29, 0.37) were associated with peak torque. Conclusions: These
      data suggest that muscle attenuation and area are independently associated with
      RTD and peak torque; and that area and attenuation demonstrate similar
      contributions to RTD.

PMID- 29342247
TI  - PEATH: single-individual haplotyping by a probabilistic evolutionary algorithm
      with toggling.
AB  - Motivation: Single-individual haplotyping (SIH) is critical in genomic
      association studies and genetic diseases analysis. However, most genomic analysis
      studies do not perform haplotype-phasing analysis due to its complexity. Several
      computational methods have been developed to solve the SIH problem, but these
      approaches have not generated sufficiently reliable haplotypes. Results: Here, we
      propose a novel SIH algorithm, called PEATH (Probabilistic Evolutionary Algorithm
      with Toggling for Haplotyping), to achieve more accurate and reliable
      haplotyping. The proposed PEATH method was compared to the most recent algorithms
      in terms of the phased length, N50 length, switch error rate and minimum error
      correction. The PEATH algorithm consistently provides the best phase and N50
      lengths, as long as possible, given datasets. In addition, verification of the
      simulation data demonstrated that the PEATH method outperforms other methods on
      high noisy data. Additionally, the experimental results of a real dataset
      confirmed that the PEATH method achieved comparable or better accuracy.
      Availability and implementation: Source code of PEATH is available at
      https://github.com/jcna99/PEATH. Contact: jkrhee@catholic.ac.kr or
      sooyong.shin@gmail.com. Supplementary information: Supplementary data are
      available at Bioinformatics online.

PMID- 29342248
TI  - Clinical considerations of the role of palbociclib in the management of advanced
      breast cancer patients with and without visceral metastases.
AB  - Background: This report assesses the efficacy and safety of palbociclib plus
      endocrine therapy (ET) in women with hormone receptor-positive, human epidermal
      growth factor receptor 2-negative advanced breast cancer (ABC) with or without
      visceral metastases. Patients and methods: Pre- and postmenopausal women with
      disease progression following prior ET (PALOMA-3; N = 521) and postmenopausal
      women untreated for ABC (PALOMA-2; N = 666) were randomized 2 : 1 to ET
      (fulvestrant or letrozole, respectively) plus palbociclib or placebo. Progression
      free survival (PFS), safety, and patient-reported quality of life (QoL) were
      evaluated by prior treatment and visceral involvement. Results: Visceral
      metastases incidence was higher in patients with prior resistance to ET (58.3%,
      PALOMA-3) than in patients naive to ET in the ABC setting (48.6%, PALOMA-2). In
      patients with prior resistance to ET and visceral metastases, median PFS (mPFS)
      was 9.2 months with palbociclib plus fulvestrant versus 3.4 months with placebo
      plus fulvestrant [hazard ratio (HR), 0.47; 95% confidence interval (CI), 0.35
      0.61], and objective response rate (ORR) was 28.0% versus 6.7%, respectively. In
      patients with nonvisceral metastases, mPFS was 16.6 versus 7.3 months, HR 0.53;
      95% CI 0.36-0.77. In patients with visceral disease and naive to ET in the
      advanced disease setting, mPFS was 19.3 months with palbociclib plus letrozole
      versus 12.9 months with placebo plus letrozole (HR 0.63; 95% CI 0.47-0.85); ORR
      was 55.1% versus 40.0%; in patients with nonvisceral disease, mPFS was not
      reached with palbociclib plus letrozole versus 16.8 months with placebo plus
      letrozole (HR 0.50; 95% CI 0.36-0.70). In patients with prior resistance to ET
      with visceral metastases, palbociclib plus fulvestrant significantly delayed
      deterioration of QoL versus placebo plus fulvestrant, whereas patient-reported
      QoL was maintained with palbociclib plus letrozole in patients naive to endocrine
      based therapy for ABC. Conclusions: Palbociclib plus ET prolonged mPFS in
      patients with visceral metastases, increased ORRs, and in patients previously
      treated for ABC, delayed QoL deterioration, presenting a standard treatment
      option among patients with visceral metastases amenable to endocrine-based
      therapy. Clinical trial registration: NCT01942135, NCT01740427.

PMID- 29342249
TI  - Splice Expression Variation Analysis (SEVA) for inter-tumor heterogeneity of gene
      isoform usage in cancer.
AB  - Motivation: Current bioinformatics methods to detect changes in gene isoform
      usage in distinct phenotypes compare the relative expected isoform usage in
      phenotypes. These statistics model differences in isoform usage in normal
      tissues, which have stable regulation of gene splicing. Pathological conditions,
      such as cancer, can have broken regulation of splicing that increases the
      heterogeneity of the expression of splice variants. Inferring events with such
      differential heterogeneity in gene isoform usage requires new statistical
      approaches. Results: We introduce Splice Expression Variability Analysis (SEVA)
      to model increased heterogeneity of splice variant usage between conditions (e.g.
      tumor and normal samples). SEVA uses a rank-based multivariate statistic that
      compares the variability of junction expression profiles within one condition to
      the variability within another. Simulated data show that SEVA is unique in
      modeling heterogeneity of gene isoform usage, and benchmark SEVA's performance
      against EBSeq, DiffSplice and rMATS that model differential isoform usage instead
      of heterogeneity. We confirm the accuracy of SEVA in identifying known splice
      variants in head and neck cancer and perform cross-study validation of novel
      splice variants. A novel comparison of splice variant heterogeneity between
      subtypes of head and neck cancer demonstrated unanticipated similarity between
      the heterogeneity of gene isoform usage in HPV-positive and HPV-negative subtypes
      and anticipated increased heterogeneity among HPV-negative samples with mutations
      in genes that regulate the splice variant machinery. These results show that SEVA
      accurately models differential heterogeneity of gene isoform usage from RNA-seq
      data. Availability and implementation: SEVA is implemented in the R/Bioconductor
      package GSReg. Contact: bahman@jhu.edu or favorov@sensi.org or ejfertig@jhmi.edu.
      Supplementary information: Supplementary data are available at Bioinformatics
      online.

PMID- 29342250
TI  - Pneumococcal Community-Acquired Pneumonia Detected by Serotype-Specific Urinary
      Antigen Detection Assays.
AB  - Background: Streptococcus pneumoniae is considered the leading bacterial cause of
      pneumonia in adults. Yet, it was not commonly detected by traditional culture
      based and conventional urinary testing in a recent multicenter etiology study of
      adults hospitalized with community-acquired pneumonia (CAP). We used novel
      serotype-specific urinary antigen detection (SSUAD) assays to determine whether
      pneumococcal cases were missed by traditional testing. Methods: We studied adult
      patients hospitalized with CAP at 5 hospitals in Chicago and Nashville (2010
      2012) and enrolled in the Etiology of Pneumonia in the Community (EPIC) study.
      Traditional diagnostic testing included blood and sputum cultures and
      conventional urine antigen detection (ie, BinaxNOW). We applied SSUAD assays that
      target serotypes included in the 13-valent pneumococcal conjugate vaccine (PCV13)
      to stored residual urine specimens. Results: Among 1736 patients with SSUAD and
      >=1 traditional pneumococcal test performed, we identified 169 (9.7%) cases of
      pneumococcal CAP. Traditional tests identified 93 (5.4%) and SSUAD identified 76
      (4.4%) additional cases. Among 14 PCV13-serotype cases identified by culture,
      SSUAD correctly identified the same serotype in all of them. Cases identified by
      SSUAD vs traditional tests were similar in most demographic and clinical
      characteristics, although disease severity and procalcitonin concentration were
      highest among those with positive blood cultures. The proportion of PCV13
      serotype cases identified was not significantly different between the first and
      second July-June study periods (6.4% vs 4.0%). Conclusions: Although restricted
      to the detection of only 13 serotypes, SSUAD testing substantially increased the
      detection of pneumococcal pneumonia among adults hospitalized with CAP.

PMID- 29342252
TI  - Triglyceride-rich lipoprotein cholesterol (TRL-C): the ugly stepsister of LDL-C.

PMID- 29342251
TI  - Kinetics of Serological Responses in Critically Ill Patients Hospitalized With
      2009 Pandemic Influenza A(H1N1) Virus Infection in Canada, 2009-2011.
AB  - Background: The kinetics of the antibody response during severe influenza are not
      well documented. Methods: Critically ill patients infected with 2009 pandemic
      influenza A(H1N1) virus (A[H1N1]pdm09), confirmed by reverse-transcription
      polymerase chain reaction analysis or seroconversion (defined as a >=4-fold rise
      in titers), during 2009-2011 in Canada were prospectively studied. Antibody
      titers in serially collected sera were determined using hemagglutinin inhibition
      (HAI) and microneutralization assays. Average antibody curves were estimated
      using linear mixed-effects models and compared by patient outcome, age, and
      corticosteroid treatment. Results: Of 47 patients with A(H1N1)pdm09 virus
      infection (median age, 47 years), 59% had baseline HAI titers of <40, and 68% had
      baseline neutralizing titers of <40. Antibody titers rose quickly after symptom
      onset, and, by day 14, 83% of patients had HAI titers of >=40, and 80% had
      neutralizing titers >=40. Baseline HAI titers were significantly higher in
      patients who died compared with patients who survived; however, the antibody
      kinetics were similar by patient outcome and corticosteroid treatment. Geometric
      mean titers over time in older patients were lower than those in younger
      patients. Conclusions: Critically ill patients with influenza A(H1N1)pdm09 virus
      infection had strong HAI and neutralizing antibody responses during their
      illness. Antibody kinetics differed by age but were not associated with patient
      outcome.

PMID- 29342253
TI  - Comparison of EQ-5D and 15D instruments for assessing the health-related quality
      of life in cardiac surgery patients.
AB  - Aims: Patient-centred outcomes can be measured with different instruments. We
      compared the performance of two health-related quality-of-life (HRQoL) measures,
      EQ-5D and 15D, in patients undergoing elective coronary artery bypass grafting
      (CABG). Methods and results: Patients who were admitted for elective CABG in
      Kuopio University Hospital Finland in 2012-14 and had completed both instruments
      concurrently as part of the admission process (n = 182). Follow-up was conducted
      by postal survey 12 months after the CABG operation. The validity, agreement, and
      responsiveness to change of both instruments were examined. The mean baseline
      HRQoL index scores obtained by the EQ-5D and the 15D were 0.795 and 0.859,
      respectively (P < 0.001 for difference). The agreement between instruments was
      poor (Spearman's rho = 0.449; P < 0.001). Observed ceiling effects at baseline
      for the EQ-5D and 15D were 31.9 and 4.4%, respectively. EQ-5D was able to
      discriminate distinct Canadian Cardiovascular Society groups. During the 1-year
      follow-up, clinically important improvement was observed in 39.6 and 53.3% of
      patients with the EQ-5D and the 15D, respectively. However, with the 15D, the
      number of operated patients required to produce one additional quality-adjusted
      life year (QALY) was more than twice as high compared with the EQ-5D. Conclusion:
      EQ-5D and 15D do not appear to be interchangeable when patient-centred outcomes
      in CABG patients are assessed. The EQ-5D seems to have better discriminative
      power and known-group validity, whereas the 15D is more sensitive to change over
      time. These instruments lead to significantly different estimates concerning the
      number of QALYs gained.

PMID- 29342255
TI  - Thoracoscopic left atrial appendage clipping as novel treatment option for peri
      device leakage.

PMID- 29342254
TI  - Distinctive Desmoplastic 3D Morphology Associated With BRAFV600E in Papillary
      Thyroid Cancers.
AB  - Context: Although 60% of papillary thyroid carcinomas are BRAFV600E mutant
      (PTCV600E), the increased aggressiveness of these cancers is still debated.
      Objective: For PTCV600E we aimed to further characterize the extent of the stroma
      and its activation, the three-dimensional (3D) tumor-stroma interface, and the
      proliferation rates of tumor and stromal fibroblasts. Design: We analyzed exomes,
      transcriptomes, and images of 364 papillary thyroid carcinoma (PTCs) from The
      Cancer Genome Atlas (TCGA), including 211 PTCV600E; stained 22 independent PTCs
      for BRAFV600E and Ki67; sequenced the exomes and stained BRAFV600E in 5 primary
      tumor blocks and 4 nodal metastases from one patient with PTCV600E; and
      reconstructed the 3D volumes of one tumor and one metastatic block at
      histological resolution. Results: In TCGA, BRAFV600E was associated with higher
      expression of proliferation markers and lower expression of thyroid
      differentiation markers, independently of tumor purity. Moreover, PTCV600E, in
      line with their overall lower purity, also had higher expression of fibroblast-
      and T cell-associated genes and presented more fibrosis. Tumor cells that
      appeared disconnected on two-dimensional histological slices were revealed to be
      part of a unique tumor component in the 3D reconstructed microvolumes, and they
      formed a surprisingly complex connected space, infiltrating a proliferative
      stroma. Finally, in our PTC set, both stromal fibroblasts and tumor cells
      presented higher proliferation rates in PTCV600E. Conclusions: Our results
      support the increased aggressiveness associated with BRAFV600E in PTC and shed
      light on the important role of the stroma in tumor expansion. The greater and
      more active fibrotic component predicts better efficiency of combined targeted
      treatments, as previously proposed for melanomaV600E.

PMID- 29342256
TI  - Comparison of pregnancy outcomes between maternity waiting home users and non
      users at hospitals with and without a maternity waiting home: retrospective
      cohort study.
AB  - Objective: To examine the impact of a maternity waiting home (MWH) by comparing
      pregnancy outcomes between users and non-users at hospitals with and without an
      MWH. Methods: We conducted a retrospective cohort study in Ethiopia comparing one
      hospital with an MWH (Attat) to a second hospital without one (Butajira). A
      structured questionnaire among sampled women in 2014 and hospital records from
      2011 to 2014 were used to compare sociodemographic characteristics and pregnancy
      outcomes between Attat MWH users and non-MWH users, Attat MWH users and Butajira,
      and Attat non-MWH users and Butajira. chi2 or ORs with 95% CIs were calculated.
      Results: Compared with Attat non-MWH users (n=306) and Butajira women (n=153),
      Attat MWH users (n=244) were more often multiparous (multipara vs primigravida:
      OR 4.43 [95% CI 2.94 to 6.68] and OR 3.58 [95% CI 2.24 to 5.73]), less educated
      (no schooling vs secondary school: OR 2.62 [95% CI 1.53 to 4.46] and OR 5.21 [95%
      CI 2.83 to 9.61], primary vs secondary school: OR 4.84 [95% CI 2.84 to 8.25] and
      OR 5.19 [95% CI 2.91 to 9.27]), poor (poor vs wealthy: OR 8.94 [95% CI 5.13 to
      15.61] and OR 12.34 [95% CI 6.78 to 22.44] and further from the hospital (2 h 27
      min vs 1 h 00 min and 1 h 12 min: OR 3.08 [95% CI 2.50 to 3.80] and OR 2.18 [95%
      CI 1.78 to 2.67]). Comparing hospital records of Attat MWH users (n=2784) with
      Attat non-users (n=5423) and Butajira women (n=9472), maternal deaths were 0 vs
      20 (0.4%; p=0.001) and 31 (0.3%; p=0.003), stillbirths 38 (1.4%) vs 393 (7.2%)
      (OR 0.18 [95% CI 0.13 to 0.25]) and 717 (7.6%) (OR 0.17 [95% CI 0.12 to 0.24])
      and uterine ruptures 2 (0.1%) vs 40 (1.1%) (OR 0.05 [95% CI 0.01 to 0.19]) and
      122 (1.8%) (OR 0.04 (95% CI 0.01 to 0.16]). No significant differences were found
      regarding maternal deaths and stillbirths between Attat non-users and Butajira
      women. Conclusions: Attat MWH users had less favourable sociodemographic
      characteristics but better birth outcomes than Attat non-users and Butajira
      women.

PMID- 29342257
TI  - Trajectories of alcohol consumption prior to the diagnosis of type 2 diabetes: a
      longitudinal case-cohort study.
AB  - Background: Non-linear associations have been reported between baseline measures
      of alcohol consumption and type 2 diabetes (T2DM). However, given that drinking
      varies over the adult life course, we investigated whether differences existed in
      the longitudinal trajectory of alcohol consumption according to T2DM status.
      Methods: For a case-cohort (916 incident cases; 7376 controls) of British civil
      servants nested within the Whitehall II cohort, the self-reported weekly volume
      of alcohol consumption was traced backwards from the date of diagnosis or
      censoring to the beginning of the study, covering a period of up to 28 years.
      Mean trajectories of alcohol intake were estimated separately by diagnosis status
      using random-effects models. Results: Drinking increased linearly among male
      cases before diagnosis, but declined among male non-cases prior to censoring. At
      the time of diagnosis or censoring, consumption among those who developed T2DM
      was 33.4 g/week greater on average. These patterns were not apparent among women.
      Here, alcohol intake among female cases was consistently below that of non-cases,
      with the difference in consumption most pronounced around 15 years prior to
      diagnosis or censoring, at ~28.0 g/week. Disparities by diagnosis status were
      attenuated following adjustment for potential confounders, including the
      frequency of consumption and metabolic factors. Drinking among male and female
      cases declined following diagnosis. Conclusions: Differences in the weekly volume
      of alcohol consumption are reported in the years leading up to diagnosis or
      censoring. Although male and female cases predominantly consumed alcohol at
      volumes lower than or equal to those who were not diagnosed, these disparities
      appear to be largely explained by a range of socio-demographic and lifestyle
      factors. Where disparities are observed between cases and non-cases, adjusted
      absolute differences are small in magnitude. The decision to drink alcohol should
      not be motivated by a perceived benefit to T2DM risk.

PMID- 29342258
TI  - Insulin and Estrogen Independently and Differentially Reduce Macronutrient Intake
      in Healthy Men.
AB  - Context: Insulin administration to the central nervous system inhibits food
      intake, but this effect has been found to be less pronounced in female compared
      with male organisms. This sex-specific pattern has been suggested to arise from a
      modulating influence of estrogen signaling on the insulin effect. Objective: We
      assessed in healthy young men whether pretreatment with transdermal estradiol
      interacts with the hypophagic effect of central nervous insulin administration
      via the intranasal pathway. Design, Setting, Participants, and Intervention:
      According to a 2*2 design, two groups of men (n = 16 in each group) received a 3
      day transdermal estradiol (100 ug/24 h) or placebo pretreatment and on two
      separate mornings were intranasally administered 160 IU regular human insulin or
      placebo. Main Outcome Measures: We assessed free-choice ad libitum calorie intake
      from a rich breakfast buffet and relevant blood parameters in samples collected
      before and after breakfast. Results: Estrogen treatment induced a 3.5-fold
      increase in serum estradiol concentrations and suppressed serum testosterone
      concentrations by 70%. Independent of estradiol administration, intranasal
      insulin reduced the intake of carbohydrates during breakfast, attenuating in
      particular the consumption of sweet, palatable foods. Estradiol treatment per se
      decreased protein consumption. We did not find indicators of eating-related
      interactions between both hormones. Conclusions: Results indicate that, in an
      acute setting, estrogen does not interact with central nervous insulin signaling
      in the control of eating behavior in healthy men. Insulin and estradiol rather
      exert independent inhibiting effects on macronutrient intake.

PMID- 29342259
TI  - False starts in 'test and start': a qualitative study of reasons for delayed
      antiretroviral therapy in Swaziland.
AB  - Background: Test and start, antiretroviral therapy (ART) for all HIV-positive
      individuals, is a WHO-recommended treatment guideline. In Swaziland, test and
      start has been evaluated through the MaxART implementation study. This article
      examines why, in MaxART, some newly diagnosed HIV-positive clients delayed
      initiating ART. Methods: Thirteen HIV-positive clients who delayed ART for >=90 d
      after testing were identified from the MaxART study database and interviewed.
      Interviews were audio recorded, transcribed and translated into English for
      qualitative content analysis. Results: Respondents had often tested positive
      several times before initiating ART, with the initial diagnosis sometimes
      completely unexpected. Repeat testing-and delayed ART-was linked to a desire to
      come to terms with their diagnosis and prepare for a lifelong treatment course.
      Clients previously enrolled in pre-ART, particularly with high CD4 counts, had
      internalized past messages about ART as being non-essential and taking care of
      oneself through other means. Concerns about ART-related adverse events were
      weighed against these messages. Worries about inadvertent disclosure and its
      impact on social and economic relationships also discouraged initiation.
      Conclusion: Although potentially reducing logistical barriers, expedited ART
      initiation does not necessarily accommodate some clients' need for time to come
      to terms with the diagnosis and the prospect of lifelong treatment.

PMID- 29342260
TI  - Interaction between Staphylococcus aureus and Pseudomonas aeruginosa is
      beneficial for colonisation and pathogenicity in a mixed biofilm.
AB  - Debate regarding the co-existence of Staphylococcus aureus and Pseudomonas
      aeruginosa in wounds remains contentious, with the dominant hypothesis describing
      a situation akin to niche partitioning, whereby both microorganisms are present
      but occupy distinct regions of the wound without interacting. In contrast, we
      hypothesised that these microorganisms do interact during early co-colonisation
      in a manner beneficial to both bacteria. We assessed competitive interaction
      between S. aureus and P. aeruginosa in biofilm cultured for 24-72 h and bacterial
      aggregates analogous to those observed in early (<24 h) biofilm formation, and
      interaction with human keratinocytes. We observed that S. aureus predominated in
      biofilm and non-attached bacterial aggregates, acting as a pioneer for the
      attachment of P. aeruginosa. We report for the first time that S. aureus mediates
      a significant (P < 0.05) increase in the attachment of P. aeruginosa to human
      keratinocytes, and that P. aeruginosa promotes an invasive phenotype in S.
      aureus. We show that co-infected keratinocytes exhibit an intermediate
      inflammatory response concurrent with impaired wound closure that is in keeping
      with a sustained proinflammatory response which allows for persistent microbial
      colonisation. These studies demonstrate that, contrary to the dominant
      hypothesis, interactions between S. aureus and P. aeruginosa may be an important
      factor for both colonisation and pathogenicity in the chronic infected wound.

PMID- 29342261
TI  - Prevalence of smoking during pregnancy and associated risk factors: a cross
      sectional study in Northern Greece.
AB  - Background: Many pregnant women smoke despite the extensive data available on the
      detrimental perinatal outcomes. The aim of this study was to estimate the
      prevalence of smoking during pregnancy and to identify the factors associated
      with smoking among pregnant women in Northern Greece. Methods: A sample of
      pregnant women (mean gestational age: 12.6 weeks) participated in a cross
      sectional study assessing the prevalence of smoking. Univariate and multivariate
      logistic regression analyses were used to examine the factors associated with
      their smoking behavior. Results: A total of 3688 pregnant women (mean age: 31.1
      +/- 5.0 years) completed the survey. On the basis of their answers, 36.1% (n =
      1330) were smokers before pregnancy and 13.2% (n = 487) were still smoking at the
      end of the first trimester. Eight hundred and forty-three women (63.4%) gave up
      smoking, apparently motivated by their pregnancy. A multivariate analysis showed
      an independent positive association of nulliparity, Greek ethnicity, age >35
      years and a BMI > 30 with smoking before pregnancy. Smoking during pregnancy was
      more common among naturally conceived pregnancies and women with a BMI >
      30.Cessation rates were lower for naturally conceived pregnancies, immigrants and
      multiparous women. Conclusion: About one third of women who smoked before
      pregnancy continued to smoke during pregnancy. Naturally conceiving, multiparous
      and immigrant women are less likely to quit smoking when pregnant. Tailored
      smoking cessation interventions should target women early in their pregnancy.

PMID- 29342262
TI  - Preliminary study of 1940 nm thulium laser usage in peroral endoscopic myotomy
      for achalasia.
AB  - Esophageal achalasia is a type of motility disorder characterized by incomplete
      relaxation of lower esophageal sphincter (LES) and absence of esophageal
      peristalsis. Peroral endoscopic myotomy (POEM) is a new treatment option for
      achalasia that is less invasive, more effective, and safe as compared to surgery.
      High-frequency electrotome is commonly used in POEM, but takes longer time to
      make the tunnel in the esophagus and causes many complications. The thulium laser
      decreases the risk of bleeding and perforation in endoscopy but has not been
      reported in digestive diseases, especially in POEM. Therefore, the aim of this
      study is to evaluate the feasibility of the 1940 nm thulium laser in POEM. From
      March 2015 to August 2015, five patients with achalasia at the Digestive
      department, Beijing Friendship Hospital, Capital Medical University, Beijing,
      China were included. Before the procedure, the patients' gender, age, and
      duration of symptoms were recorded. Eckardt symptom score and LES thickness,
      which measured by endoscopic ultrasonography, were recorded. While the subtypes
      of achalasia (according to the Chicago classification), lower esophagus sphincter
      resting pressure (LESRP) and integrated relaxation pressure (IRP) were measured
      by HRM for all patients. Barium esophagram was also used to rule out anatomical
      lesions, esophageal varices, or neoplasia, which may cause similar symptoms. All
      examinations were performed one week before POEM. POEM was performed with the
      1940 nm thulium laser under general anesthesia. Eckardt score, procedure
      duration, myotomy length, and complications were recorded one week after POEM.
      All the patients were followed-up at two weeks and four weeks after POEM. POEM
      was successfully performed in all five patients. The mean age of the patients was
      38.8 years (24-54 years). Achalasia subtypes were type I (n = 1), II (n = 2), and
      III (n = 2). The operation duration was 186, 180, 111, 75, and 126 minutes for
      the five cases. Pre/postprocedure Eckardt scores were 3/0, 7/0, 5/1, 6/0, and
      9/0. Pre/postprocedure LESRP (mmHg) were 45.3/26.4, 18.0/1.1, 25.8/10.4,
      16.5/11.2, and 24.2/20.8. Pre/postprocedure IRP (mmHg) were 27.3/15.5, 15.4/4.2,
      5.7/6.8, 15.5/10.1, and 13.1/14, respectively. No adverse events occurred during
      the procedure. After POEM, subcutaneous emphysema occurred in case 1 on the first
      day, which relieved spontaneously after two days without special intervention.
      Infection occurred in case 5 on the day of POEM was healed with antibiotics three
      days later. The 1940 nm thulium laser is feasible for POEM procedure. Further
      studies are needed to determine whether the 1940 nm thulium laser is better than
      high-frequency electrotome.

PMID- 29342263
TI  - Sri Lanka's post-tsunami health system recovery: a qualitative analysis of
      physician perspectives.
AB  - Background: The 2004 Indian Ocean tsunami caused significant damage to the health
      system in Sri Lanka. Rebuilding infrastructure and improving the mental health
      system were targets of recovery policies. Retrospective analyses of the post
      tsunami health system recovery in Sri Lanka lack the perspectives of local
      stakeholders, including health care providers. Methods: In 2014 we interviewed 23
      Sri Lankan physicians from the Eastern and Southern regions. Participants were
      recruited with snowball sampling. We used a content analysis approach in
      analysing the transcriptions. Results: Sri Lankan physicians critiqued
      governance, sustainability and equity in the health system recovery. They held
      leadership roles as facilitators and sustainers of specific projects but were
      rarely formally consulted in recovery strategic planning. They identified
      instances of poor coordination among partners, corruption trends, local resource
      mismatches, regional resource disparities and the influence of the Sri Lankan
      civil war. Conclusions: Post-tsunami health system recovery planning and
      implementation in Sri Lanka did not involve local physician stakeholders in ways
      that have been prioritized more recently in other recovery frameworks. Despite
      limited formal inclusion, local physicians developed significant leadership roles
      that have informed their critical perspectives on the health system recovery.

PMID- 29342265
TI  - Oesophageal duplication cyst mimicking cardiac mass.

PMID- 29342264
TI  - Effect of Continuous Glucose Monitoring on Glycemic Control, Acute Admissions,
      and Quality of Life: A Real-World Study.
AB  - Context: Randomized controlled trials evaluating real-time continuous glucose
      monitoring (RT-CGM) patients with type 1 diabetes (T1D) show improved glycemic
      control, but limited data are available on real-world use. Objective: To assess
      impact of RT-CGM in real-world settings on glycemic control, hospital admissions,
      work absenteeism, and quality of life (QOL). Design: Prospective, observational,
      multicenter, cohort study. Participants: A total of 515 adults with T1D on
      continuous subcutaneous insulin infusion (CSII) therapy starting in the Belgian
      RT-CGM reimbursement program. Intervention: Initiation of RT-CGM reimbursement.
      Main Outcome Measure: Hemoglobin A1c (HbA1c) evolution from baseline to 12
      months. Results: Between September 1, 2014, and December 31, 2016, 515 adults
      entered the reimbursement system. Over this period, 417 (81%) patients used RT
      CGM for at least 12 months. Baseline HbA1c was 7.7 +/- 0.9% (61 +/- 9.8 mmol/mol)
      and decreased to 7.4 +/- 0.8% (57 +/- 8.7 mmol/mol) at 12 months (P < 0.0001).
      Subjects who started RT-CGM because of insufficient glycemic control showed
      stronger decrease in HbA1c at 4, 8, and 12 months compared with patients who
      started because of hypoglycemia or pregnancy. In the year preceding
      reimbursement, 16% of patients were hospitalized for severe hypoglycemia or
      ketoacidosis in contrast to 4% (P < 0.0005) the following year, with decrease in
      admission days from 54 to 18 per 100 patient years (P < 0.0005). In the same
      period, work absenteeism decreased and QOL improved significantly, with strong
      decline in fear of hypoglycemia. Conclusion: Sensor-augmented pump therapy in
      patients with T1D followed in specialized centers improves HbA1c, fear of
      hypoglycemia, and QOL, whereas work absenteeism and admissions for acute diabetes
      complications decreased.

PMID- 29342267
TI  - Safety of Single-Dose Primaquine in G6PD-Deficient and G6PD-Normal Males in Mali
      Without Malaria: An Open-Label, Phase 1, Dose-Adjustment Trial.
AB  - Background: The World Health Organization recommendation on the use of a single
      low dose of primaquine (SLD-PQ) to reduce Plasmodium falciparum malaria
      transmission requires more safety data. Methods: We conducted an open-label,
      nonrandomized, dose-adjustment trial of the safety of 3 single doses of
      primaquine in glucose-6-phosphate dehydrogenase (G6PD)-deficient adult males in
      Mali, followed by an assessment of safety in G6PD-deficient boys aged 11-17 years
      and those aged 5-10 years, including G6PD-normal control groups. The primary
      outcome was the greatest within-person percentage drop in hemoglobin
      concentration within 10 days after treatment. Results: Fifty-one participants
      were included in analysis. G6PD-deficient adult males received 0.40, 0.45, or
      0.50 mg/kg of SLD-PQ. G6PD-deficient boys received 0.40 mg/kg of SLD-PQ. There
      was no evidence of symptomatic hemolysis, and adverse events considered related
      to study drug (n = 4) were mild. The mean largest within-person percentage change
      in hemoglobin level between days 0 and 10 was -9.7% (95% confidence interval
      [CI], -13.5% to -5.90%) in G6PD-deficient adults receiving 0.50 mg/kg of SLD-PQ, 
      11.5% (95% CI, -16.1% to -6.96%) in G6PD-deficient boys aged 11-17 years, and 
      9.61% (95% CI, -7.59% to -13.9%) in G6PD-deficient boys aged 5-10 years. The
      lowest hemoglobin concentration at any point during the study was 92 g/L.
      Conclusion: SLD-PQ doses between 0.40 and 0.50 mg/kg were well tolerated in G6PD
      deficient males in Mali. Clinical Trials Registration: NCT02535767.

PMID- 29342266
TI  - Causes, Patterns, and Severity of Androgen Excess in 1205 Consecutively Recruited
      Women.
AB  - Context: Androgen excess in women is predominantly due to underlying polycystic
      ovary syndrome (PCOS). However, there is a lack of clarity regarding patterns and
      severity of androgen excess that should be considered predictive of non-PCOS
      pathology. Objective: We examined the diagnostic utility of simultaneous
      measurement of serum dehydroepiandrosterone sulfate (DHEAS), androstenedione
      (A4), and testosterone (T) to delineate biochemical signatures and cutoffs
      predictive of non-PCOS disorders in women with androgen excess. Design:
      Retrospective review of all women undergoing serum androgen measurement at a
      large tertiary referral center between 2012 and 2016. Serum A4 and T were
      measured by tandem mass spectrometry and DHEAS by immunoassay. Patients with at
      least one increased serum androgen underwent phenotyping by clinical notes
      review. Results: In 1205 women, DHEAS, A4, and T were measured simultaneously.
      PCOS was the most common diagnosis in premenopausal (89%) and postmenopausal
      women (29%). A4 was increased in all adrenocortical carcinoma (ACC) cases (n =
      15) and T in all ovarian hyperthecosis (OHT) cases (n = 7); all but one case of
      congenital adrenal hyperplasia (CAH; n = 18) were identified by increased levels
      of A4 and/or T. In premenopausal women, CAH was a prevalent cause of severe A4
      (59%) and T (43%) excess; severe DHEAS excess was predominantly due to PCOS
      (80%). In postmenopausal women, all cases of severe DHEAS and A4 excess were
      caused by ACC and severe T excess equally by ACC and OHT. Conclusions: Pattern
      and severity of androgen excess are important predictors of non-PCOS pathology
      and may be used to guide further investigations as appropriate.

PMID- 29342268
TI  - Reduced Expression of Mismatch Repair Genes MSH6/MSH2 Directly Promotes Pituitary
      Tumor Growth via the ATR-Chk1 Pathway.
AB  - Context: The mechanisms of pituitary adenoma (PA) pathogenesis and proliferation
      remain largely unknown. Objectives: To clarify the role of mismatch repair (MMR)
      genes in the molecular mechanism of PA proliferation. Design: We performed
      quantitative analyses by real-time polymerase chain reaction and
      immunohistochemistry to detect MMR gene and protein expression in human PAs (n =
      47). We also performed correlation analyses of expression levels and tumor volume
      doubling time (TVDT; n = 31). Specifically, correlation analyses were performed
      between genes with significant correlation and ataxiatelangiectasia and Rad3
      related (ATR) expression in cell-cycle regulatory mechanism ATR-checkpoint kinase
      1 (Chk1) pathway (n = 93). We investigated the effect of reduced gene expression
      on cell proliferation and ATR gene expression in AtT-20ins cells and primary
      cultures of human PAs. Results: Expression of mutS homologs 6 and 2 (MSH6 and
      MSH2) was positively associated with TVDT (R = 0.52, P = 0.003, and R = 0.44, P =
      0.01), as were the corresponding protein levels. Gene expression was positively
      associated with ATR expression (R = 0.47, P < 0.00001, and R = 0.49, P <
      0.00001). In AtT-20ins, the reduction of MSH6 and/or MSH2 expression by small
      interfering RNA significantly promoted cell proliferation by decreasing ATR
      expression. This effect was also observed in primary culture. Conclusion:
      Reduction of MSH6 and MSH2 expression at the messenger RNA and protein levels
      could be involved in direct PA proliferation by promoting cell-cycle progression
      or decreasing the rate of apoptosis through interference with the function of the
      ATR-Chk1 pathway.

PMID- 29342269
TI  - A Silent Epidemic: The Prevalence, Incidence and Persistence of Mycoplasma
      genitalium Among Young, Asymptomatic High-Risk Women in the United States.
AB  - Background: Mycoplasma genitalium can result in pelvic inflammatory disease and
      adverse pregnancy outcomes. We analyzed data collected from a prospective study
      of asymptomatic bacterial vaginosis (BV) to determine the natural history of M.
      genitalium. Methods: Women aged 15-25 years, with asymptomatic BV and >=2 risk
      factors for sexually transmitted infection were recruited from 10 sites
      throughout the United States. Vaginal swab samples were collected at enrollment
      and through home-based testing every 2 months over 12 months. M. genitalium
      nucleic acid amplification testing was performed for M. genitalium using
      transcription-mediated assays (Hologic). The prevalence, incidence, and
      persistence of M. genitalium, defined as all positive specimens during follow-up,
      were estimated with 95% confidence intervals (CIs). Adjusted odds ratios (AOR)
      were calculated using logistic and Poisson regression to evaluate participant
      characteristics associated with M. genitalium infection. Results: Among 1139
      women, 233 were M. genitalium positive, for a prevalence of 20.5% (95% CI, 18.2%
      22.9%); 42 of 204 had persistent M. genitalium (20.6%). Among 801 M. genitalium
      negative women at baseline, the M. genitalium incidence was 36.6 per 100 person
      years (95% CI, 32.4-41.3). Black race (AOR, 1.92; 95% CI, 1.09-3.38), age <=21
      years (1.40; 1.03-1.91), and prior pregnancy (1.36; 1.00-1.85) were associated
      with prevalent M. genitalium; only black race was associated with incident M.
      genitalium (P = .03). Conclusions: We identified high rates of prevalent,
      incident, and persistent M. genitalium infections among young, high-risk women
      with asymptomatic BV, supporting the need for clinical trials to evaluate the
      impact of M. genitalium screening on female reproductive health outcomes.

PMID- 29342270
TI  - Whole-genome analysis reveals the evolution and transmission of an MDR
      DH/NAP11/106 Clostridium difficile clone in a paediatric hospital.
AB  - Background: Clostridium difficile strain DH/NAP11/106, a relatively antibiotic
      susceptible strain, is now the most common cause of C. difficile infection (CDI)
      among adults in the USA. Objectives: To identify mechanisms underlying the
      evolution and transmission of an MDR DH/NAP11/106 clone. Methods: WGS (Illumina
      MiSeq), restriction endonuclease analysis (REA) and antibiotic susceptibility
      testing were performed on 134 C. difficile isolates collected from paediatric
      patients with CDI over a 2 year period. Results: Thirty-one of 134 (23%) isolates
      were REA group DH. Pairwise single-nucleotide variant (SNV) analyses identified a
      DH clone causing seven instances of CDI in two patients. During the 337 days
      between the first and second CDI, Patient 1 (P1) received 313 days of antibiotic
      therapy. Clindamycin and rifaximin resistance, and reduced vancomycin
      susceptibility (MIC 0.5-2 mg/L), were newly identified in the relapsed isolate.
      This MDR clone was transmitted to Patient 2 (P2) while P1 and P2 received care in
      adjacent private rooms. P1 and P2 each developed two additional CDI relapses.
      Comparative genomics analyses demonstrated SNVs in multiple antibiotic resistance
      genes, including rpoB (rifaximin resistance), gyrB and a gene encoding PBP; gyrB
      and PBP mutations did not consistently confer a resistance phenotype. The clone
      also acquired a 46 000 bp genomic element, likely a conjugative plasmid, which
      contained ermB (clindamycin resistance). The element shared 99% identity with the
      genomic sequence of Faecalibacterium prausnitzii, an enteric commensal.
      Conclusions: These data highlight the emergence of MDR in C. difficile strain
      DH/NAP11/106 through multiple independent mechanisms probably as a consequence of
      profound antibiotic pressure.

PMID- 29342271
TI  - MELODI: Mining Enriched Literature Objects to Derive Intermediates.
AB  - Background: The scientific literature contains a wealth of information from
      different fields on potential disease mechanisms. However, identifying and
      prioritizing mechanisms for further analytical evaluation presents enormous
      challenges in terms of the quantity and diversity of published research. The
      application of data mining approaches to the literature offers the potential to
      identify and prioritize mechanisms for more focused and detailed analysis.
      Methods: Here we present MELODI, a literature mining platform that can identify
      mechanistic pathways between any two biomedical concepts. Results: Two case
      studies demonstrate the potential uses of MELODI and how it can generate
      hypotheses for further investigation. First, an analysis of ETS-related gene ERG
      and prostate cancer derives the intermediate transcription factor SP1, recently
      confirmed to be physically interacting with ERG. Second, examining the
      relationship between a new potential risk factor for pancreatic cancer identifies
      possible mechanistic insights which can be studied in vitro. Conclusions: We have
      demonstrated the possible applications of MELODI, including two case studies.
      MELODI has been implemented as a Python/Django web application, and is freely
      available to use at [www.melodi.biocompute.org.uk].

PMID- 29342272
TI  - Daily decision-making about food during pregnancy: a New Zealand study.
AB  - Pregnancy has always been a life-changing event for women and their families, but
      societal concern about pregnancy and motherhood has become intense in the digital
      age. The role of health promotion agencies and others supplying health-related
      resources about lifestyle behaviours is both important and in need of scrutiny.
      Ever increasing advice for pregnant women, their families and health
      professionals, abounds. This study of decision making during pregnancy
      investigated how women made everyday decisions during pregnancy about food and
      drink, as well as dietary supplements and medications, alcohol and recreational
      drugs. This qualitative interview study was a side-arm to a double-blind
      randomized, placebo-controlled trial conducted with pregnant women in Wellington
      New Zealand, 2013-2016. Data from interviews with 20 women were analysed using
      inductive thematic analysis. In relation to decision-making about lifestyle
      behaviours, five themes emerged-Information about food; Wanted and unwanted
      advice; Worry, anxiety and indecision; Making daily decisions about food; Changes
      in decision making over time. Participating women talked more about food
      selection and restriction advice than any other lifestyle topic. Analysis
      demonstrated concern about information accuracy and overload from multiple,
      diverse sources. Women described learning how to assess resource credibility, how
      to develop decision-making skills, and who to trust. The study raises important
      questions about how the health information environment, despite best intentions,
      can be confusing or potentially harmful. The study underlines the continued
      importance of the role health professionals have in not only interpreting
      information to discuss individualized advice, but also in empowering pregnant
      women to develop lifestyle-related decision-making skills.

PMID- 29342273
TI  - Hypermethylation of EIF4E promoter is associated with early onset of gastric
      cancer.
AB  - Although gastric cancer (GC) in young adults (<= 45 years) accounts for fewer
      than 10% of newly diagnosed cases, the young patients are more likely to have
      advanced disease at presentation compared with elderly patients. Previous studies
      have identified that the DNA methylation of genomes are different during aging.
      Our study aimed to explore the association between DNA methylation and the onset
      of GC. We applied Illumina HumanMethylation450 BeadChip to examine methylation
      expression profiles and compared methylation expression patterns in five early
      onset GC patients and seven elderly patients. Additionally, we evaluated the
      associations of methylation expression with different clinicopathological
      characteristics of GC. Our results showed that the pattern of genome-wide
      methylation expression was significantly different between early onset and
      elderly GC. The top 10 hypomethylation and hypermethylation CpG sites were
      selected for further analyses in The Cancer Genome Atlas (TCGA) database. We
      found that the hypermethylation of cg11037477, located at the promoter of EIF4E,
      was significantly associated with age at diagnosis and the expression of EIF4E.
      Besides, GC patients with high level of cg11037477 were more likely to have
      advance disease with T3/T4 invasion and III/IV stage. The cg11037477
      hypermethylation and EIF4E down-expression were significantly related to poor
      survival of GC patients. Our study provides new insights into the molecular
      mechanism of early onset patients with GC and suggests that methylation of
      cg11037477 and expression of EIF4E may act as prognostic markers in GC.

PMID- 29342274
TI  - Editorial.

PMID- 29342276
TI  - A Predictive, Quantitative Model of Spiking Activity and Stimulus-Secretion
      Coupling in Oxytocin Neurons.
AB  - Oxytocin neurons of the rat hypothalamus project to the posterior pituitary,
      where they secrete their products into the bloodstream. The pattern and quantity
      of that release depends on the afferent inputs to the neurons, on their intrinsic
      membrane properties, and on nonlinear interactions between spiking activity and
      exocytosis: A given number of spikes will trigger more secretion when they arrive
      close together. Here we present a quantitative computational model of oxytocin
      neurons that can replicate the results of a wide variety of published
      experiments. The spiking model mimics electrophysiological data of oxytocin cells
      responding to cholecystokinin (CCK), a peptide produced in the gut after food
      intake. The secretion model matches results from in vitro experiments on stimulus
      secretion coupling in the posterior pituitary. We mimic the plasma clearance of
      oxytocin with a two-compartment model, replicating the dynamics observed
      experimentally after infusion and injection of oxytocin. Combining these models
      allows us to infer, from measurements of oxytocin in plasma, the spiking activity
      of the oxytocin neurons that produced that secretion. We have tested these
      inferences with experimental data on oxytocin secretion and spiking activity in
      response to intravenous injections of CCK. We show how intrinsic mechanisms of
      the oxytocin neurons determine this relationship: In particular, we show that the
      presence of an afterhyperpolarization (AHP) in oxytocin neurons dramatically
      reduces the variability of their spiking activity and even more markedly reduces
      the variability of oxytocin secretion. The AHP thus acts as a filter, protecting
      the final product of oxytocin cells from noisy fluctuations.

PMID- 29342275
TI  - Hot-spot KIF5A mutations cause familial ALS.
AB  - Heterozygous missense mutations in the N-terminal motor or coiled-coil domains of
      the kinesin family member 5A (KIF5A) gene cause monogenic spastic paraplegia
      (HSP10) and Charcot-Marie-Tooth disease type 2 (CMT2). Moreover, heterozygous de
      novo frame-shift mutations in the C-terminal domain of KIF5A are associated with
      neonatal intractable myoclonus, a neurodevelopmental syndrome. These findings,
      together with the observation that many of the disease genes associated with
      amyotrophic lateral sclerosis disrupt cytoskeletal function and intracellular
      transport, led us to hypothesize that mutations in KIF5A are also a cause of
      amyotrophic lateral sclerosis. Using whole exome sequencing followed by rare
      variant analysis of 426 patients with familial amyotrophic lateral sclerosis and
      6137 control subjects, we detected an enrichment of KIF5A splice-site mutations
      in amyotrophic lateral sclerosis (2/426 compared to 0/6137 in controls; P = 4.2 *
      10-3), both located in a hot-spot in the C-terminus of the protein and predicted
      to affect splicing exon 27. We additionally show co-segregation with amyotrophic
      lateral sclerosis of two canonical splice-site mutations in two families.
      Investigation of lymphoblast cell lines from patients with KIF5A splice-site
      mutations revealed the loss of mutant RNA expression and suggested
      haploinsufficiency as the most probable underlying molecular mechanism.
      Furthermore, mRNA sequencing of a rare non-synonymous missense mutation
      (predicting p.Arg1007Gly) located in the C-terminus of the protein shortly
      upstream of the splice donor of exon 27 revealed defective KIF5A pre-mRNA
      splicing in respective patient-derived cell lines owing to abrogation of the
      donor site. Finally, the non-synonymous single nucleotide variant rs113247976
      (minor allele frequency = 1.00% in controls, n = 6137), also located in the C
      terminal region [p.(Pro986Leu) in exon 26], was significantly enriched in
      familial amyotrophic lateral sclerosis patients (minor allele frequency = 3.40%;
      P = 1.28 * 10-7). Our study demonstrates that mutations located specifically in a
      C-terminal hotspot of KIF5A can cause a classical amyotrophic lateral sclerosis
      phenotype, and underline the involvement of intracellular transport processes in
      amyotrophic lateral sclerosis pathogenesis.

PMID- 29342277
TI  - Finding Nemo: hybrid assembly with Oxford Nanopore and Illumina reads greatly
      improves the clownfish (Amphiprion ocellaris) genome assembly.
AB  - Background: Some of the most widely recognized coral reef fishes are clownfish or
      anemonefish, members of the family Pomacentridae (subfamily: Amphiprioninae).
      They are popular aquarium species due to their bright colours, adaptability to
      captivity, and fascinating behavior. Their breeding biology (sequential
      hermaphrodites) and symbiotic mutualism with sea anemones have attracted much
      scientific interest. Moreover, there are some curious geographic-based phenotypes
      that warrant investigation. Leveraging on the advancement in Nanopore long read
      technology, we report the first hybrid assembly of the clown anemonefish
      (Amphiprion ocellaris) genome utilizing Illumina and Nanopore reads, further
      demonstrating the substantial impact of modest long read sequencing data sets on
      improving genome assembly statistics. Results: We generated 43 Gb of short
      Illumina reads and 9 Gb of long Nanopore reads, representing approximate genome
      coverage of 54* and 11*, respectively, based on the range of estimated k-mer
      predicted genome sizes of between 791 and 967 Mbp. The final assembled genome is
      contained in 6404 scaffolds with an accumulated length of 880 Mb (96.3% BUSCO
      calculated genome completeness). Compared with the Illumina-only assembly, the
      hybrid approach generated 94% fewer scaffolds with an 18-fold increase in N50
      length (401 kb) and increased the genome completeness by an additional 16%. A
      total of 27 240 high-quality protein-coding genes were predicted from the clown
      anemonefish, 26 211 (96%) of which were annotated functionally with information
      from either sequence homology or protein signature searches. Conclusions: We
      present the first genome of any anemonefish and demonstrate the value of low
      coverage (~11*) long Nanopore read sequencing in improving both genome assembly
      contiguity and completeness. The near-complete assembly of the A. ocellaris
      genome will be an invaluable molecular resource for supporting a range of
      genetic, genomic, and phylogenetic studies specifically for clownfish and more
      generally for other related fish species of the family Pomacentridae.

PMID- 29342278
TI  - DOSIMETRY OF ADULT AND PEDIATRIC PATIENTS FOR COMMON DIGITAL RADIOGRAPHY
      EXAMINATIONS.
AB  - The present work reports dosimetry data on adult and pediatric patients for some
      common radiographic examinations during the standard hospital routine. The
      measurements are the part of quality assurance program to determine radiation
      exposures to patients in these examinations. The entrance skin doses (ESDs) of
      the patients were measured from 2451 projection for 12 diagnostic examinations in
      digital radiography (DR). The ESDs in adult patient were measured using
      thermoluminescence dosemeters placed on the skin of the patient. In pediatric
      patients, ESDs were evaluated from the measured air kerma with ionization
      chamber, patient specific parameters and known values of machine exposure factors
      during examinations. The third quartile values of ESDs are proposed as local
      diagnostic reference levels (LDRLs) for radiographic examinations having
      statistical significant number of exposures (n >= 20). The proposed LDRL values
      are also compared with earlier published LDRL/DRL values.

PMID- 29342279
TI  - Incidence and predictors of post-transplant lymphoproliferative disease after
      kidney transplantation during adulthood and childhood: a registry study.
AB  - Background: Differences in the epidemiology of post-transplant
      lymphoproliferative disease (PTLD) between adult and paediatric kidney transplant
      recipients remain unclear. Methods: Using the Australian and New Zealand Dialysis
      and Transplant Registry (1963-2015), the cumulative incidences of PTLD in
      children (age <20 years) and adults were calculated using a competing risk of
      death model and compared with age-matched population-based data using
      standardized incidence ratios (SIRs). Risk factors for PTLD were assessed using
      Cox proportional hazards regression. Results: Among 23 477 patients (92% adult,
      60% male), 505 developed PTLD, with 50 (10%) occurring in childhood recipients.
      The 25-year cumulative incidence of PTLD was 3.3% [95% confidence interval (CI)
      2.9-3.6] for adult recipients and 3.6% (95% CI 2.7-4.8) for childhood recipients.
      Childhood recipients had a 30-fold increased risk of lymphoma compared with the
      age-matched general population [SIR 29.5 (95% CI 21.9-38.8)], higher than adult
      recipients [SIR 8.4 (95% CI 7.7-9.2)]. Epstein-Barr virus (EBV)-negative
      recipient serology [adjusted hazard ratio (aHR) 3.33 (95% CI 2.21-5.01), P <
      0.001], year of transplantation [aHR 0.93 for each year after the year 2000 (95%
      CI 0.88-0.99), P = 0.02], induction with an agent other than anti-CD25 monoclonal
      antibody [aHR 2.07 (95% CI 1.16-3.70), P = 0.01] and having diabetes [aHR 3.49
      (95% CI 2.26-5.38), P < 0.001] were independently associated with PTLD.
      Conclusions: Lymphoma occurs at similar rates in adult and paediatric recipients,
      but has been decreasing since the year 2000. EBV-negative patients and those with
      diabetes or induction agent other than anti-CD25 monoclonal antibody are at
      substantially increased risk of PTLD.

PMID- 29342281
TI  - Phenotypic analysis of HIV-1 E157Q integrase polymorphism and impact on
      virological outcome in patients initiating an integrase inhibitor-based regimen.
AB  - Objectives: To assess the phenotypic susceptibility of the E157Q polymorphism in
      HIV-1 integrase (IN) and the virological outcome of patients infected with E157Q
      mutated virus initiating an IN inhibitor (INI)-based regimen. Methods: This was a
      multicentre study assessing IN sequences from INI-naive patients among 17 French
      HIV clinical centres. E157Q site-directed mutants in pNL4.3 and pCRF02_AG
      contexts were assessed in a recombinant phenotypic assay. Results: Prevalence of
      the E157Q polymorphism was 2.7% among 8528 IN sequences from INI-naive patients
      and its distribution was 1.7%, 5.6% and 2.2% in B, CRF02_AG and various non-B
      subtypes, respectively. Thirty-nine INI-naive patients with E157Q-mutated virus
      initiated an INI-based regimen. Among them, 15 had a viral load (VL) <50
      copies/mL at initiation and virological suppression was maintained during the
      first year of follow-up in all but two exhibiting a viral blip. Twenty-four
      patients had a VL > 50 copies/mL at the time of INI-based regimen initiation.
      Among them eight were receiving a first-line regimen and the only two patients
      who did not reach VL < 50 copies/mL at week 24 were receiving elvitegravir. The
      16 remaining patients were ART experienced in virological failure with drug
      resistant viruses displaying several virological outcomes independently of the
      genotypic susceptibility score. Phenotypic analyses showed a fold change in EC50
      of 0.6, 0.9 and 1.9 for raltegravir, dolutegravir and elvitegravir, respectively,
      in a subtype B context, and 1.1, 1.9 and 2.4 for raltegravir, dolutegravir and
      elvitegravir, respectively, in a CRF02_AG context. Conclusions: Assessment of
      virological response in 39 patients initiating an INI-based regimen with E157Q
      mutated virus, in combination with phenotypic analysis, suggests that particular
      attention should be paid to antiretroviral-naive patients and dolutegravir should
      be preferentially used in these patients.

PMID- 29342280
TI  - Epigenetic Differentiation of Natural Populations of Lilium bosniacum Associated
      with Contrasting Habitat Conditions.
AB  - Epigenetic variation in natural populations with contrasting habitats might be an
      important element, in addition to the genetic variation, in plant adaptation to
      environmental stress. Here, we assessed genetic, epigenetic, and cytogenetic
      structure of the three Lilium bosniacum populations growing on distinct habitats.
      One population was growing under habitual ecological conditions for this species
      and the other two were growing under stress associated with high altitude and
      serpentine soil. Amplified fragment length polymorphism and methylation-sensitive
      amplification polymorphism analyses revealed that the three populations did not
      differentiate genetically, but were clearly separated in three distinct clusters
      according to DNA methylation profiles. Principal coordinate analysis showed that
      overall epigenetic variation was closely related to habitat conditions. A new
      methylation-sensitive amplification polymorphism scoring approach allowed
      identification of mainly unmethylated (phiST = 0.190) and fully CpG methylated
      (phiST = 0.118) subepiloci playing a role in overall population differentiation,
      in comparison with hemimethylated sites (phiST = 0.073). In addition, unusual
      rDNA repatterning and the presence of B chromosomes bearing 5S rDNA loci were
      recorded in the population growing on serpentine soil, suggesting dynamic
      chromosome rearrangements probably linked to global genome demethylation, which
      might have reactivated some mobile elements. We discuss our results considering
      our earlier data on morphology and leaf anatomy of several L. bosniacum
      populations, and suggest a possible role of epigenetics as a key element in
      population differentiation associated with environmental stress in these
      particular lily populations.

PMID- 29342282
TI  - Membrane fluxes, bypass flows, and sodium stress in rice: the influence of
      silicon.
AB  - Provision of silicon (Si) to roots of rice (Oryza sativa L.) can alleviate salt
      stress by blocking apoplastic, transpirational bypass flow of Na+ from root to
      shoot. However, little is known about how Si affects Na+ fluxes across cell
      membranes. Here, we measured radiotracer fluxes of 24Na+, plasma membrane
      depolarization, tissue ion accumulation, and transpirational bypass flow, to
      examine the influence of Si on Na+ transport patterns in hydroponically grown,
      salt-sensitive (cv. IR29) and salt-tolerant (cv. Pokkali) rice. Si increased
      growth and lowered [Na+] in shoots of both cultivars, with minor effects in
      roots; neither root nor shoot [K+] were affected. In IR29, Si lowered shoot [Na+]
      via a large reduction in bypass flow, while in Pokkali, where bypass flow was
      small and not affected by Si, this was achieved mainly via a growth dilution of
      shoot Na+. Si had no effect on unidirectional 24Na+ fluxes (influx and efflux),
      or on Na+-stimulated plasma-membrane depolarization, in either IR29 or Pokkali.
      We conclude that, while Si can reduce Na+ translocation via bypass flow in some
      (but not all) rice cultivars, it does not affect unidirectional Na+ transport or
      Na+ cycling in roots, either across root cell membranes or within the bulk root
      apoplast.

PMID- 29342284
TI  - Two Ways to Kill a Patient.
AB  - According to the Standard View, a doctor who withdraws life-sustaining treatment
      does not kill the patient but rather allows the patient to die-an important
      distinction, according to some. I argue that killing (and causing death) can be
      understood in either of two ways, and given the relevant understanding, the
      Standard View is insulated from typical criticisms. I conclude by noting several
      problems for the Standard View that remain to be fully addressed.

PMID- 29342283
TI  - Non-typhoidal Salmonella serovars associated with invasive and non-invasive
      disease in the Lao People's Democratic Republic.
AB  - Background: Invasive non-typhoidal Salmonella (iNTS) disease is a well-described
      cause of mortality in children and human immunodeficiency virus (HIV)-infected
      adults in sub-Saharan Africa. Additionally, there is an ill-defined burden of
      iNTS disease in Southeast Asia. Methods: Aiming to investigate the causative
      serovars of non-invasive and iNTS disease and their associated antimicrobial
      susceptibility profiles in the Lao People's Democratic Republic, we performed
      multilocus sequence typing and antimicrobial susceptibility profiling on 168 NTS
      (63 blood and 105 faecal) organisms isolated in Lao between 2000 and 2012.
      Results: Six different serovars were isolated from blood; Salmonella enterica
      serovar Enteritidis (n=28), S. enterica serovar Typhimurium (n=19) and S.
      enterica serovar Choleraesuis (n=11) accounted for >90% (58/63) of the iNTS
      disease cases. In contrast, the isolates from diarrhoeal faeces were comprised of
      18 different serovars, the mostly commonly identified being S. enterica
      Typhimurium (n=28), S. enterica Weltevreden (n=14) and S. enterica Stanley
      (n=15). S. enterica Enteritidis and S. enterica Choleraesuis were significantly
      more associated with systemic disease than diarrhoeal disease in this patient
      group (p<0.001). Conclusions: We find a differing distribution of Salmonella
      sequence types/serovars between those causing iNTS disease and non-invasive
      disease in Lao. We conclude that there is a small but not insignificant burden of
      iNTS disease in Lao. Further clinical and epidemiological investigations are
      required to assess mortality and the role of comorbidities such as HIV.

PMID- 29342285
TI  - Serial Participation and the Ethics of Phase 1 Healthy Volunteer Research.
AB  - Phase 1 healthy volunteer clinical trials-which financially compensate subjects
      in tests of drug toxicity levels and side effects-appear to place pressure on
      each joint of the moral framework justifying research. In this article, we review
      concerns about phase 1 trials as they have been framed in the bioethics
      literature, including undue inducement and coercion, unjust exploitation, and
      worries about compromised data validity. We then revisit these concerns in light
      of the lived experiences of serial participants who are income-dependent on phase
      1 trials. We show how participant experiences shift attention from discrete
      exchanges, behaviors, and events in the research enterprise to the ongoing and
      dynamic patterns of serial participation in which individual decision-making is
      embedded in collective social and economic conditions and shaped by institutional
      policies. We argue in particular for the ethical significance of structurally
      diminished voluntariness, routine powerlessness in setting the terms of exchange,
      and incentive structures that may promote pharmaceutical interests but encourage
      phase 1 healthy volunteers to skirt important rules.

PMID- 29342286
TI  - The Ethics of General Population Preventive Genomic Sequencing: Rights and Social
      Justice.
AB  - Advances in DNA sequencing technology open new possibilities for public health
      genomics, especially in the form of general population preventive genomic
      sequencing (PGS). Such screening programs would sit at the intersection of public
      health and preventive health care, and thereby at once invite and resist the use
      of clinical ethics and public health ethics frameworks. Despite their
      differences, these ethics frameworks traditionally share a central concern for
      individual rights. We examine two putative individual rights-the right not to
      know, and the child's right to an open future-frequently invoked in discussions
      of predictive genetic testing, in order to explore their potential contribution
      to evaluating this new practice. Ultimately, we conclude that traditional
      clinical and public health ethics frameworks, and these two rights in particular,
      should be complemented by a social justice perspective in order adequately to
      characterize the ethical dimensions of general population PGS programs.

PMID- 29342288
TI  - Association between ABCG2 rs2231142 and poor response to allopurinol: replication
      and meta-analysis.
AB  - Objective: ABCG2 rs2231142 (Q141K) has been reported to be associated with poor
      response to allopurinol, while there are conflicting data on the association
      between the genetically independent ABCG2 rs10011796 variant and allopurinol
      response. The aim of this study was to replicate the association of ABCG2
      rs2231142 and rs10011796 with allopurinol response and perform a meta-analysis.
      Methods: Participants in the Long-term Allopurinol Safety Study Evaluating
      Outcomes in Gout Patients (LASSO) (n = 299) were studied. In patients with
      evidence of adherence to allopurinol therapy (plasma oxypurinol >20 MUmol/l),
      good response was defined as serum urate <6 mg/dl on allopurinol ?300 mg/day and
      poor response as serum urate ? 6 mg/dl despite allopurinol >300 mg/day.
      Association of rs2231142 and rs10011796 with poor response was tested in logistic
      regression models that included age, sex, BMI, ethnicity and estimated glomerular
      filtration rate. Results from the LASSO study and a subset of participants in the
      Genetics of Gout in Aotearoa New Zealand study (n = 296, including 264 from a
      previously published report) were combined by meta-analysis. Results: There was
      evidence for association of rs2231142 with allopurinol response [odds ratio (OR)
      = 2.35, P = 7.3 * 10-4] but not for rs10011796 (OR = 1.21, P = 0.33) in the LASSO
      cohort using an adjusted logistic regression model. Meta-analysis provided
      evidence of a significant association of rs2231142 with allopurinol response (OR
      = 2.43, P = 6.2 * 10-7), but not rs10011796 (OR = 1.06, P = 0.69). Conclusion:
      This study has confirmed the significant association of ABCG2 rs2231142 with poor
      response to allopurinol.

PMID- 29342290
TI  - Chronic kidney disease and stroke: more observations but no trials.

PMID- 29342287
TI  - To the Brain and Back: Migratory Paths of Dendritic Cells in Multiple Sclerosis.
AB  - Migration of dendritic cells (DC) to the central nervous system (CNS) is a
      critical event in the pathogenesis of multiple sclerosis (MS). While up until
      now, research has mainly focused on the transmigration of DC through the blood
      brain barrier, experimental evidence points out that also the choroid plexus and
      meningeal vessels represent important gateways to the CNS, especially in early
      disease stages. On the other hand, DC can exit the CNS to maintain immunological
      tolerance to patterns expressed in the CNS, a process that is perturbed in MS.
      Targeting trafficking of immune cells, including DC, to the CNS has demonstrated
      to be a successful strategy to treat MS. However, this approach is known to
      compromise protective immune surveillance of the brain. Unravelling the migratory
      paths of regulatory and pathogenic DC within the CNS may ultimately lead to the
      design of new therapeutic strategies able to selectively interfere with the
      recruitment of pathogenic DC to the CNS, while leaving host protective mechanisms
      intact.

PMID- 29342289
TI  - Recent advances in kidney transplantation: a viewpoint from the Descartes
      advisory board.
AB  - Transplantation medicine is a rapidly evolving field. Keeping afloat of the
      published literature to offer the best clinical care to our patients is a
      daunting task. As part of its educational mission, the Descartes advisory board
      identified seven topics in kidney transplantation where there has been
      substantial progresses over the last years: kidney allocation within
      Eurotransplant; kidney exchange strategies; kidney machine perfusion strategies;
      the changing landscape of anti-human leukocyte antigen (HLA) antibodies; the new
      immunosuppressive drugs in the pipeline; strategies for immunosuppression
      minimization; and the continuous enigma of focal segmental glomerular sclerosis
      recurrence after transplantation. Here, we have summarized the main knowledge and
      the main challenges of these seven topics with the aim to provide transplant
      professionals at large with key bullet points to successfully understand these
      new concepts.

PMID- 29342291
TI  - PORTUGUESE STUDY OF MEAN GLANDULAR DOSE IN MAMMOGRAPHY AND COMPARISON WITH
      EUROPEAN REFERENCES.
AB  - To characterise the mean glandular dose (MGD) in a sample of healthcare providers
      for digital mammography in Portugal. To compare the achieved values with European
      references. The MGD was measured on a poly-methyl-methacrylate phantom (45 mm)
      for each system using dosimeters. In addition, MGD was estimated using exposure
      settings collected from mammography exams in clinical context. Data were
      collected from 25 computed-radiography systems (CR) and 13 integrated digital
      (DR). For both measurements (phantom and clinical exposures), the average MGD for
      CR was higher compared to the DR. For CR the mean MGD was 1.85 mGy (CC
      projection) and 2.10 mGy (MLO projection). For DR systems the corresponding
      values were 1.54 mGy (CC) and 1.68 mGy (MLO). The average MGD obtained using both
      methods and for both technologies is within the acceptable reference range
      proposed by European guidelines (<2.5 mGy). Dose Reference Levels implementation
      should be the next step to optimise mammography practice in Portugal.

PMID- 29342292
TI  - Clinical utility of the global anti-phospholipid syndrome score for risk
      stratification: a pooled analysis.
AB  - Objective: Recently, our group conceived a risk score for clinical manifestations
      of APS (the global APS score, or GAPSS) that takes into account the combination
      of independent cardiovascular risk factors and the aPL positivity profile. These
      include hyperlipidaemia, arterial hypertension, aCL, anti-beta2 glycoprotein-I,
      aPS-PT and the LA. A complementary version, the adjusted GAPSS (aGAPSS), which
      excludes aPS-PT, was also designed. The aim of our study was to systematically
      review the literature to assess the clinical utility of the GAPSS and aGAPSS for
      risk stratification of any APS clinical manifestation. Methods: We pooled data
      from available cohort studies, including a total of 10 studies, comprising 2273
      patients, in which the GAPSS has been applied. A search strategy was developed a
      priori to identify an available cohort that reported findings which investigated
      the clinical utility of GAPSS or aGAPSS. Results: Seven studies used the GAPSS in
      their cohort, whereas three studies used the aGAPSS. In brief, we found a
      statistically significant difference in the cumulative GAPSS and aGAPSS between
      patients that experienced an arterial and/or venous thrombotic event [cumulative
      mean GAPSS (s.d.) 10.6 (4.74) and aGAPSS 7.6 (3.95)], patients without any
      thrombotic manifestation [cumulative GAPSS 7.01 (5.46) and aGAPSS 4.9 (4.33)] and
      patients with pregnancy morbidity [cumulative GAPSS 8.79 (2.59) and aGAPSS 6.7
      (2.8)]. The highest levels of GAPSS were found in patients that experienced
      arterial thrombosis [mean GAPSS 12.2 (5.2)] and patients that experienced any
      recurrences of clinical manifestations of APS [mean GAPSS 13.7 (3.1)].
      Conclusion: GAPSS may represent a useful tool to assess the thrombosis or
      pregnancy loss risk in aPL-positive patients, switching from the concept of aPL
      as a sole diagnostic antibody to aPL as risk factors for clinical events.

PMID- 29342293
TI  - Genetic Analyses in Small-for-Gestational-Age Newborns.
AB  - Context: Small for gestational age (SGA) can be the result of fetal growth
      restriction, which is associated with perinatal morbidity and mortality.
      Mechanisms that control prenatal growth are poorly understood. Objective: The aim
      of the current study was to gain more insight into prenatal growth failure and
      determine an effective diagnostic approach in SGA newborns. We hypothesized that
      one or more copy number variations (CNVs) and disturbed methylation and sequence
      variants may be present in genes associated with fetal growth. Design: A
      prospective cohort study of subjects with a low birth weight for gestational age.
      Setting: The study was conducted at an academic pediatric research institute.
      Patients: A total of 21 SGA newborns with a mean birth weight below the first
      centile and a control cohort of 24 appropriate-for-gestational-age newborns were
      studied. Interventions: Array comparative genomic hybridization, genome-wide
      methylation studies, and exome sequencing were performed. Main Outcome Measures:
      The numbers of CNVs, methylation disturbances, and sequence variants. Results:
      The genetic analyses demonstrated three CNVs, one systematically disturbed
      methylation pattern, and one sequence variant explaining SGA. Additional
      methylation disturbances and sequence variants were present in 20 patients. In 19
      patients, multiple abnormalities were found. Conclusion: Our results confirm the
      influence of a large number of mechanisms explaining dysregulation of fetal
      growth. We concluded that CNVs, methylation disturbances, and sequence variants
      all contribute to prenatal growth failure. These genetic workups can be an
      effective diagnostic approach in SGA newborns.

PMID- 29342294
TI  - Factors affecting public health nurses' satisfaction with the preparedness and
      response of disaster relief operations at nuclear emergencies.

PMID- 29342295
TI  - Empagliflozin Treatment Is Associated With Improved beta-Cell Function in Type 2
      Diabetes Mellitus.
AB  - Objective: To examine whether lowering plasma glucose concentration with the
      sodium-glucose transporter-2 inhibitor empagliflozin improves beta-cell function
      in patients with type 2 diabetes mellitus (T2DM). Methods: Patients with T2DM (N
      = 15) received empagliflozin (25 mg/d) for 2 weeks. beta-Cell function was
      measured with a nine-step hyperglycemic clamp (each step, 40 mg/dL) before and at
      48 hours and at 14 days after initiating empagliflozin. Results: Glucosuria was
      recorded on days 1 and 14 [mean +/- standard error of the mean (SEM), 101 +/- 10
      g and 117 +/- 11 g, respectively] after initiating empagliflozin, as were
      reductions in fasting plasma glucose levels (25 +/- 6 mg/dL and 38 +/- 8 mg/dL,
      respectively; both P < 0.05). After initiating empagliflozin and during the
      stepped hyperglycemic clamp, the incremental area under the plasma C-peptide
      concentration curve increased by 48% +/- 12% at 48 hours and 61% +/- 10% at 14
      days (both P < 0.01); glucose infusion rate increased by 15% on day 3 and 16% on
      day 14, compared with baseline (both P < 0.05); and beta-cell function, measured
      with the insulin secretion/insulin resistance index, increased by 73% +/- 21% at
      48 hours and 112% +/- 20% at 14 days (both P < 0.01). beta-cell glucose
      sensitivity during the hyperglycemic clamp was enhanced by 42% at 14 hours and
      54% at 14 days after initiating empagliflozin (both P < 0.01). Conclusion:
      Lowering the plasma glucose concentration with empagliflozin in patients with
      T2DM augmented beta-cell glucose sensitivity and improved beta-cell function.

PMID- 29342297
TI  - AN EXACT GOODNESS-OF-FIT TEST BASED ON THE OCCUPANCY PROBLEMS TO STUDY ZERO
      INFLATION AND ZERO-DEFLATION IN BIOLOGICAL DOSIMETRY DATA.
AB  - The goal in biological dosimetry is to estimate the dose of radiation that a
      suspected irradiated individual has received. For that, the analysis of
      aberrations (most commonly dicentric chromosome aberrations) in scored cells is
      performed and dose response calibration curves are built. In whole body
      irradiation (WBI) with X- and gamma-rays, the number of aberrations in samples is
      properly described by the Poisson distribution, although in partial body
      irradiation (PBI) the excess of zeros provided by the non-irradiated cells leads,
      for instance, to the Zero-Inflated Poisson distribution. Different methods are
      used to analyse the dosimetry data taking into account the distribution of the
      sample. In order to test the Poisson distribution against the Zero-Inflated
      Poisson distribution, several asymptotic and exact methods have been proposed
      which are focused on the dispersion of the data. In this work, we suggest an
      exact test for the Poisson distribution focused on the zero-inflation of the data
      developed by Rao and Chakravarti (Some small sample tests of significance for a
      Poisson distribution. Biometrics 1956; 12 : 264-82.), derived from the problems
      of occupancy. An approximation based on the standard Normal distribution is
      proposed in those cases where the computation of the exact test can be tedious. A
      Monte Carlo Simulation study was performed in order to estimate empirical
      confidence levels and powers of the exact test and other tests proposed in the
      literature. Different examples of applications based on in vitro data and also
      data recorded in several radiation accidents are presented and discussed. A Shiny
      application which computes the exact test and other interesting goodness-of-fit
      tests for the Poisson distribution is presented in order to provide them to all
      interested researchers.

PMID- 29342298
TI  - Periodontal Disease Assessed Using Clinical Dental Measurements and Cancer Risk
      in the ARIC Study.
AB  - Background: While evidence is increasingly consistent with a positive association
      between periodontitis and cancer risk, most studies have relied on self-reported
      periodontitis. In this study, we prospectively evaluated the association of
      periodontal disease severity with cancer risk in black and white older adults in
      a cohort study that included a dental examination. Methods: Included were 7466
      participants in the Atherosclerosis Risk in Communities study cohort who at visit
      4 (1996-1998) reported being edentulous or underwent the dental examination.
      Probing depth and gingival recession were measured at six sites on all teeth;
      these measurements were used to define periodontal disease severity. Incident
      cancers (n = 1648) and cancer deaths (n = 547) were ascertained during a median
      of 14.7 years of follow-up. All statistical tests were two-sided. Results: An
      increased risk of total cancer (hazard ratio [HR] = 1.24, 95% confidence interval
      [CI] = 1.07 to 1.44, Ptrend = .004) was observed for severe periodontitis (>30%
      of sites with attachment loss >3 mm) compared with no/mild periodontitis (<10% of
      sites with attachment loss >3 mm), adjusting for smoking and other factors.
      Strong associations were observed for lung cancer (HR = 2.33, 95% CI = 1.51 to
      3.60, Ptrend < .001), and elevated risks were noted for colorectal cancer for
      severe periodontitis, which were significant among never smokers (HR = 2.12, 95%
      CI = 1.00 to 4.47). Associations were generally weaker, or not apparent among
      black participants, except for lung and colorectal cancers, where associations
      were similar by race. No associations were observed for breast, prostate, or
      hematopoietic and lymphatic cancer risk. Conclusions: This study provides
      additional evidence that cancer risk, especially for lung and colorectal cancer,
      is elevated in individuals with periodontitis. Additional research is needed to
      understand cancer site-specific and racial differences in findings.

PMID- 29342299
TI  - Benefit of left atrial appendage electrical isolation for persistent and long
      standing persistent atrial fibrillation: a systematic review and meta-analysis.
AB  - Aims: The long-term outcomes of left atrial appendage electrical isolation
      (LAAEI) in patients with non-paroxysmal atrial fibrillation (AF) have
      corroborated the significant role of the LAA in this arrhythmia. We sought to
      investigate the incremental benefit of LAAEI in patients undergoing catheter
      ablation for persistent AF or long-standing persistent AF (LSPAF). Methods and
      results: A systematic review of Medline, Cochrane, and Embase for all the
      clinical studies in which assessment LAAEI in non-paroxysmal AF patients was
      performed. The benefit of LAAEI in patients with AF was analysed from seven
      studies that enrolled a total of 930 patients [mean age 63 +/- 5 years; male:
      69%]. All studies included patients with either persistent AF or LSPAF or the
      combination of them. The overall freedom from all-arrhythmia recurrence at 12
      months of follow-up off antiarrhythmic medications in patients who underwent
      LAAEI was 75.5% vs. 43.9% in those in whom only standard ablation was performed
      [56% relative reduction and 31.6% absolute reduction; risk ratio (RR) 0.44, 95%
      confidence interval (95% CI) 0.31-0.64; P < 0.0001]. The rate of ischaemic stroke
      in the LAAEI group was 0.4% and in the control group 2.1% at 12 months follow-up
      (RR 0.40, 95% CI 0.12-1.30; P = 0.13). Acute complications rates were identical
      between groups [LAAEI 5.5%, control 5.5% (RR 0.99, 95% CI 0.46-2.16; P = 0.99)].
      Conclusion: Left atrial appendage electrical isolation in addition to standard
      ablation appears to have a substantial incremental benefit to achieve freedom
      from ALL atrial arrhythmias in patients with persistent AF and LSPAF without
      increasing acute procedural complications and without raising the risk of
      ischaemic stroke.

PMID- 29342301
TI  - Subtyping Bladder Cancers: Biology vs Bioinformatics.

PMID- 29342300
TI  - Metastatic joint involvement or inflammatory arthritis? A conundrum with immune
      checkpoint inhibitor-related adverse events.

PMID- 29342302
TI  - Determination of the appropriate physical density of internal metallic ports in
      temporary tissue expanders for the treatment planning of post-mastectomy
      radiation therapy.
AB  - Some patients undergoing breast reconstruction require post-mastectomy radiation
      therapy, but the metallic ports used in temporary tissue expanders attenuate the
      X-rays. In this study, we evaluated by the film method, the attenuation of 4 MV
      and 6 MV X-rays after passing through a metallic port, with the aim of
      identifying a useful method for determining the appropriate density to use in the
      radiation treatment planning system (RTPS), taking into account the distance
      between the metallic port and the targets. Radiochromic film was used to measure
      depth doses after the X-rays passed through the metallic port. The physical
      density allotted to the metal port portion was varied on the RTPS within the
      range 1-16 g/cm3, and the physical density values were calculated that best
      reproduced the depth-dose distribution extrapolated from the film method. When
      the metallic port was orientated perpendicularly, the attenuation of the X-rays
      peaked at ~7% at both 4 MV and 6 MV. In the parallel orientation, the X-rays were
      attenuated by up to ~40% at 4 MV and by up to ~30% at 6 MV. We estimated the
      optimum physical density to be 9.8 g/cm3, which yielded the best fit with the
      actual measurements. We demonstrated the most likely range for the target depth
      from the CT images of actual patients and, within this range, we identified the
      optimum physical density at which the measured and calculated values were most
      consistent with each other.

PMID- 29342303
TI  - Biomarkers for Tobacco Exposures, Toxicology, Regulation, and Cessation.

PMID- 29342304
TI  - Introduction of standardised tobacco packaging during a 12-month transition
      period: Findings from small retailers in the United Kingdom.
AB  - Introduction: Factory-made cigarettes (FMC) and roll-your-own (RYO) tobacco have
      had to be produced in standardised packaging since 20th May 2016 in the United
      Kingdom, with a minimum pack size of 20 sticks for FMC and 30 grams for RYO.
      Manufacturers and retailers were given a 12-month transition period. Methods: An
      observational study was conducted using monthly Electronic Point of Sale data
      from 500 small retailers in England, Scotland, and Wales, between May 2016 and
      May 2017. The 20 top selling tobacco products (15 FMC, 5 RYO) were monitored to
      observe when standardised packs were first introduced, the proportion of
      retailers selling each fully branded and standardised product, and the average
      number of monitored fully branded and standardised products sold by each
      retailer. The number of unique tobacco-related product codes sold by each
      retailer was also recorded each month. Results: Eighteen of the fully branded
      products continued to be sold throughout the transition period and no
      standardised variants were sold in the first five months. It was not until month
      eleven that the average number of standardised products sold by retailers
      exceeded the fully branded products. The average number of unique tobacco-related
      product codes sold by each retailer decreased by a third over the transition
      period. Conclusions: Tobacco companies used the transition period to delay the
      removal of fully branded products and gradually introduce standardised variants.
      This staggered introduction may have mitigated some of the immediate intended
      effects of the legislation by desensitising consumers to new pack designs.
      Implications: Evaluation research from countries which have introduced
      standardised packaging for tobacco products is key to help inform future
      implementation. This is the first study to monitor the transition from fully
      branded to standardised products using real-time retail data. The findings
      demonstrate that tobacco companies delayed the introduction of standardised
      products and removal of fully branded packaging. Countries seeking to introduce
      standardised packaging should consider what length of transition is allowed, as
      the protracted 12 month period in the UK appeared longer than needed to
      transition stockholding and may have mitigated immediate intended effects by
      desensitising consumers to new pack designs.

PMID- 29342305
TI  - ANALYSIS OF ELECTRIC FIELD STRENGTH AND POWER AROUND SELECTED MOBILE BASE
      STATIONS.
AB  - The analysis of channel power and electric field strength at various locations
      from mobile base stations using power sensor, spectrum analyzer and log-periodic
      antenna revealed maximum potential exposure between the range of 61.1 and 254.7
      m. Generally, the potential exposure values ranged from 0.0717 to 0.8950 mW m-2
      with a maximum deviation of 22.22%. GSM900 was found to be more pronounced than
      GSM1800 and UMTS2100. Though the results complied with ICNIRP reference levels
      with a wide margin of 0.01%, it was higher than some previous work and South
      African mean value of 0.16 mW m-2, agreed with similar work elsewhere but lower
      than a global average value of 0.730 mW m-2.

PMID- 29342306
TI  - Prevalence and Factors Associated with Diarrhoea among Children between 6 and 59
      Months of Age in Mwanza City Tanzania.
AB  - Background: Childhood diarrhoea is a global public health problem especially in
      unplanned settlements of low- and middle-income countries. Different studies have
      associated household settlement and childhood diarrhoea, but the prevalence and
      risk factors associated with childhood diarrhoea at the community level are not
      clearly known. Method: A community-based cross-sectional study was performed to
      determine the prevalence and risk factors associated with diarrhoea in among 480
      children between 6 and 59 months of age in Mwanza city from June to August 2016.
      Risk factors associated with childhood diarrhoea in Mwanza city were determined
      using univariate, bivariate and multivariate analysis. Results: The study showed
      a prevalence of diarrhoea of 20.4% and an association between type of settlement
      and childhood diarrhoea (p < 0.001) in a chi-square analysis. During bivariate
      analysis, and logistic regression, after controlling for other factors, unplanned
      settlement was significantly associated with childhood diarrhoea (odds
      ratio=3.475, p < 0.001 and AOR=3.469, p < 0.001). Other factors associated with
      childhood diarrhoea were behaviour of mother washing hands before preparing food
      (AOR = 0, 193, p < 0.001), mother washing hands after changing child's napkins
      (AOR = 0.544, p < 0.036) and the behaviour of the child washing hands after
      toilet (AOR = 0.447, p < 0.006). Conclusion: Risk factors associated with
      childhood diarrhoea in Mwanza city are unplanned settlement and behaviour of
      mother and child washing hands during critical time; hence, continuous community
      health promotion insisting on washing hands with soap and water during critically
      time is the best method for fighting childhood diarrhoea in Mwanza city.

PMID- 29342308
TI  - Chronic kidney disease burden among African migrants in three European countries
      and in urban and rural Ghana: the RODAM cross-sectional study.
AB  - Background: Chronic kidney disease (CKD) is a major burden among sub-Saharan
      African (SSA) populations. However, differences in CKD prevalence between rural
      and urban settings in Africa, and upon migration to Europe are unknown. We
      therefore assessed the differences in CKD prevalence among homogenous SSA
      population (Ghanaians) residing in rural and urban Ghana and in three European
      cities, and whether conventional risk factors of CKD explained the observed
      differences. Furthermore, we assessed whether the prevalence of CKD varied among
      individuals with hypertension and diabetes compared with individuals without
      these conditions. Methods: For this analysis, data from Research on Obesity &
      Diabetes among African Migrants (RODAM), a multi-centre cross-sectional study,
      were used. The study included a random sample of 5607 adult Ghanaians living in
      Europe (1465 Amsterdam, 577 Berlin, 1041 London) and Ghana (1445 urban and 1079
      rural) aged 25-70 years. CKD status was defined according to severity of kidney
      disease using the combination of glomerular filtration rate (G1-G5) and
      albuminuria (A1-A3) levels as defined by the 2012 Kidney Disease: Improving
      Global Outcomes severity classification. Comparisons among sites were made using
      logistic regression analysis. Results: CKD prevalence was lower in Ghanaians
      living in Europe (10.1%) compared with their compatriots living in Ghana (13.3%)
      even after adjustment for age, sex and conventional risk factors of CKD [adjusted
      odds ratio (OR) = 0.70, 95% confidence interval (CI) 0.56-0.88, P = 0.002]. CKD
      prevalence was markedly lower among Ghanaian migrants with hypertension (adjusted
      OR = 0.54, 0.44-0.76, P = 0.001) and diabetes (adjusted OR = 0.37, 0.22-0.62, P =
      0.001) compared with non-migrant Ghanaians with hypertension and diabetes. No
      significant differences in CKD prevalence was observed among non-migrant
      Ghanaians and migrant Ghanaians with no hypertension and diabetes. Among Ghanaian
      residents in Europe, the odds of CKD were lower in Amsterdam than in Berlin,
      while among Ghanaian residents in Ghana, the odds of CKD were lower in rural
      Ghana (adjusted OR = 0.68, 95% CI 0.53-0.88, P = 0.004) than in urban Ghana, but
      these difference were explained by conventional risk factors. Conclusion: Our
      study shows important differences in CKD prevalence among Ghanaians living in
      Europe compared with those living in Ghana, independent of conventional risk
      factors, with marked differences among those with hypertension and diabetes.
      Further research is needed to identify factors that might explain the observed
      difference across sites to implement interventions to reduce the high burden of
      CKD, especially in rural and urban Ghana.

PMID- 29342307
TI  - Using Phylogenomic Data to Explore the Effects of Relaxed Clocks and Calibration
      Strategies on Divergence Time Estimation: Primates as a Test Case.
AB  - Primates have long been a test case for the development of phylogenetic methods
      for divergence time estimation. Despite a large number of studies, however, the
      timing of origination of crown Primates relative to the Cretaceous-Paleogene (K
      Pg) boundary and the timing of diversification of the main crown groups remain
      controversial. Here, we analysed a data set of 372 taxa (367 Primates and 5
      outgroups, 3.4 million aligned base pairs) that includes nine primate genomes. We
      systematically explore the effect of different interpretations of fossil
      calibrations and molecular clock models on primate divergence time estimates. We
      find that even small differences in the construction of fossil calibrations can
      have a noticeable impact on estimated divergence times, especially for the oldest
      nodes in the tree. Notably, choice of molecular rate model (autocorrelated or
      independently distributed rates) has an especially strong effect on estimated
      times, with the independent rates model producing considerably more ancient age
      estimates for the deeper nodes in the phylogeny. We implement thermodynamic
      integration, combined with Gaussian quadrature, in the program MCMCTree, and use
      it to calculate Bayes factors for clock models. Bayesian model selection
      indicates that the autocorrelated rates model fits the primate data substantially
      better, and we conclude that time estimates under this model should be preferred.
      We show that for eight core nodes in the phylogeny, uncertainty in time estimates
      is close to the theoretical limit imposed by fossil uncertainties. Thus, these
      estimates are unlikely to be improved by collecting additional molecular sequence
      data. All analyses place the origin of Primates close to the K-Pg boundary,
      either in the Cretaceous or straddling the boundary into the Palaeogene.

PMID- 29342310
TI  - Temporal Trends of Sources of Cigarettes among U.S. High School Students: 2001
      2015.
AB  - Introduction: Restricting the supply of cigarettes to youth plays an important
      role in reducing youth smoking. Methods: The study included data from 8 years of
      the national Youth Risk Behavior Survey (YRBS) from 2001 to 2015 with 99,572 high
      school students less than 18 years old. Data were weighted to provide national
      estimates of the temporal trends of cigarette sources. Each cigarette source was
      analyzed by a separate multivariable logistic regression model and the linear
      trend odds ratio (aOR) was adjusted by age, sex, race/ethnicity, and smoking
      frequency. Results: The current smoking prevalence among U.S. high school
      students less than 18 years of age declined from 26.9% in 2001 to 9.9% in 2015.
      Among current smokers, we found an overall downward trend of buying cigarettes in
      a store (aOR=0.98, CI [0.96 - 1.00]) and an overall upward trend of getting them
      "some other way" (aOR=1.03, CI [1.01 - 1.05]). The prevalence of purchasing
      cigarettes in a store significantly declined among smokers aged 16-17, male
      smokers, white smokers, and daily smokers, but not among other categories. The
      prevalence of getting cigarettes "some other way" significantly increased across
      all groups except Hispanic smokers and medium-level or daily smokers.
      Conclusions: The proportion of high school students reporting that they bought
      cigarettes from a store has been declining over the years, while the proportion
      of high schoolers reporting that they got cigarettes "some other way" has been
      increasing. The temporal trends also varied by age, sex, race/ethnicity, and
      smoking frequency. Implications: Patterns of high school student access to
      cigarettes have changed from 2001 to 2015, with access from "some other way"
      becoming more prevalent. The differences in cigarette acquisition by age, sex,
      race/ethnicity, and smoking frequency highlight the importance of implementing
      tailored policies and interventions to reduce youth access to cigarettes and
      prevent youth from smoking. Clinical Trial Registration: This is not a clinical
      trial.

PMID- 29342309
TI  - Prognostic Power of a Tumor Differentiation Gene Signature for Bladder Urothelial
      Carcinomas.
AB  - Background: Muscle-invasive bladder cancers (MIBCs) cause approximately 150 000
      deaths per year worldwide. Survival for MIBC patients is heterogeneous, with no
      clinically validated molecular markers that predict clinical outcome. Non-MIBCs
      (NMIBCs) generally have favorable outcome; however, a portion progress to MIBC.
      Hence, development of a prognostic tool that can guide decision-making is crucial
      for improving clinical management of bladder urothelial carcinomas. Methods:
      Tumor grade is defined by pathologic evaluation of tumor cell differentiation,
      and it often associates with clinical outcome. The current study extrapolates
      this conventional wisdom and combines it with molecular profiling. We developed
      an 18-gene signature that molecularly defines urothelial cellular
      differentiation, thus classifying MIBCs and NMIBCs into two subgroups: basal and
      differentiated. We evaluated the prognostic capability of this "tumor
      differentiation signature" and three other existing gene signatures including the
      The Cancer Genome Atlas (TCGA; 2707 genes), MD Anderson Cancer Center (MDA; 2252
      genes/2697 probes), and University of North Carolina at Chapel Hill (UNC; 47
      genes) using five gene expression data sets derived from MIBC and NMIBC patients.
      All statistical tests were two-sided. Results: The tumor differentiation
      signature demonstrated consistency and statistical robustness toward stratifying
      MIBC patients into different overall survival outcomes (TCGA cohort 1, P = .03;
      MDA discovery, P = .009; MDA validation, P = .01), while the other signatures
      were not as consistent. In addition, we analyzed the progression (Ta/T1
      progressing to >=T2) probability of NMIBCs. NMIBC patients with a basal tumor
      differentiation signature associated with worse progression outcome (P = .008).
      Gene functional term enrichment and gene set enrichment analyses revealed that
      genes involved in the biologic process of immune response and inflammatory
      response are among the most elevated within basal bladder cancers, implicating
      them as candidates for immune checkpoint therapies. Conclusions: These results
      provide definitive evidence that a biology-prioritizing clustering methodology
      generates meaningful insights into patient stratification and reveals targetable
      molecular pathways to impact future therapeutic approach.

PMID- 29342311
TI  - Nonmotor manifestations in ALS patients with tracheostomy and invasive
      ventilation.

PMID- 29342312
TI  - Maladaptive repetitive thought as a transdiagnostic phenomenon and treatment
      target: An integrative review.
AB  - OBJECTIVE: Maladaptive repetitive thought (RT), the frequent and repetitive
      revisiting of thoughts or internal experiences, is associated with a range of
      psychopathological processes and disorders. We present a synthesis of prior
      research on maladaptive RT and develop a framework for elucidating and
      distinguishing between five forms of maladaptive RT. METHOD: In addition to the
      previously studied maladaptive RT (worry, rumination, and obsession), this
      framework is used to identify two additional forms of maladaptive RT (yearning
      and interoceptive RT). We then present a review of extant psychotherapy
      intervention research targeting maladaptive RT, focusing both on specific
      empirically based treatment strategies, and also constructs within treatments
      that impact maladaptive RT. CONCLUSION: The paper concludes with recommendations
      for future basic and intervention research on maladaptive RT and related
      psychopathologies.

PMID- 29342313
TI  - Collagen XII myopathy with rectus femoris atrophy and collagen XII retention in
      fibroblasts.
AB  - INTRODUCTION: Mutation in the collagen XII gene (COL12A1) was recently reported
      to induce Bethlem myopathy. We describe a family affected by collagen XII-related
      myopathy in 3 generations. METHODS: Systematic interview, clinical examination,
      skin biopsies, and MRI of muscle were used. RESULTS: The phenotype was
      characterized by neonatal hypotonia, contractures, and delayed motor development
      followed by resolution of contractures and a motor performance limited by reduced
      endurance. DNA analyses revealed a novel donor splice-site mutation in COL12A1
      (c.8100 + 2T>C), which segregated with clinical affection and abnormal collagen
      XII retention in fibroblasts. MRI disclosed a selective wasting of the rectus
      femoris muscle. DISCUSSION: COL12A1 mutations should be considered in patients
      with a mild Bethlem phenotype who present with selective wasting of the rectus
      femoris, absence of the outside-in phenomenon on MRI, and abnormal collagen XII
      retention in fibroblasts. Muscle Nerve 57: 1026-1030, 2018.

PMID- 29342314
TI  - Fatigue is a relevant outcome in patients with myasthenia gravis.
AB  - INTRODUCTION: Patients with myasthenia gravis often experience fatigue, but its
      effect on quality of life (QoL) is underestimated, and fatigue is rarely measured
      in clinical trials. METHODS: Two hundred fifty-seven myasthenic patients
      completed the Neuro-QoL-Fatigue and measures of disease severity and QoL. We
      studied the relationship between fatigue and clinical and demographic variables.
      Finally, we studied the responsiveness of the Neuro-QoL-Fatigue in 95 patients
      receiving treatments for myasthenia and estimated the minimal important
      difference (MID). RESULTS: Fatigue correlated with greater disease severity (r =
      0.52-0.69, P < 0.0001) and worse QoL (r = 0.65-0.75, P < 0.0001). Patients in
      remission, with minimal manifestations, and pure ocular symptoms reported minimal
      fatigue. Regression modeling showed that, in addition to its relationship with
      disease severity, fatigue was worse in females, patients with generalized
      disease, and those with anxiety/depression. Fatigue improved after
      immunomodulation (P < 0.0001), and the MID was 5.3 points. DISCUSSION: Fatigue in
      myasthenia correlates with disease severity, affects QoL, and can improve after
      treatment. Muscle Nerve 58: 197-203, 2018.

PMID- 29342315
TI  - Oxidation of Methylalumoxane Oligomers.
AB  - The anions formed from methylalumoxane (MAO) and suitable donors (e.g.
      octamethyltrisiloxane) are amenable to mass spectrometric (MS) analysis. Their
      composition as deduced from this data allows direct insight into the chemical
      transformations of their neutral precursors. One such process is oxidation, which
      is well-known to be facile for MAO without any clear idea of what actually occurs
      at a molecular level. Addition of O2 to MAO results in immediate gelation, but MS
      analysis reveals no corresponding change to the composition of the principal
      oligomeric anions. A slow (hours) reaction does occur that involves net
      incorporation of Me2 AlOMe into the oligomeric anions, and the identities of the
      OMe-containing anions were confirmed by 1 H NMR spectroscopy, MS/MS analysis, and
      addition of an authentic sample of Me2 AlOMe to MAO. The result tallies with the
      fact that addition of O2 to MAO produces Me2 AlOMe from free Me3 Al which
      eventually leads to formation of oxidized MAO oligomers and changes in ion
      abundance. Aging of the oxygenated MAO results in further growth of the oligomers
      similar to that of the non-oxidized species. Mass spectrometric analysis
      therefore reveals useful insights into the environmental history of a given MAO
      batch.

PMID- 29342316
TI  - Solvent-Free Enzyme Activity: Quick, High-Yielding Mechanoenzymatic Hydrolysis of
      Cellulose into Glucose.
AB  - Mechanochemistry enables enzymatic cleavage of cellulose into glucose without
      bulk solvents, acids, other aggressive reagents, or substrate pre-treatment. This
      clean mechanoenzymatic process (coined RAging) is also directly applicable to
      biomass, avoids many limitations associated with the use of cellulases, and
      produces glucose concentrations greater than three times that obtained by
      conventional methods.

PMID- 29342317
TI  - Osteoblast-like MC3T3-E1 Cells Prefer Glycolysis for ATP Production but Adipocyte
      like 3T3-L1 Cells Prefer Oxidative Phosphorylation.
AB  - Mesenchymal stromal cells (MSCs) are early progenitors that can differentiate
      into osteoblasts, chondrocytes, and adipocytes. We hypothesized that osteoblasts
      and adipocytes utilize distinct bioenergetic pathways during MSC differentiation.
      To test this hypothesis, we compared the bioenergetic profiles of preosteoblast
      MC3T3-E1 cells and calvarial osteoblasts with preadipocyte 3T3L1 cells, before
      and after differentiation. Differentiated MC3T3-E1 osteoblasts met adenosine
      triphosphate (ATP) demand mainly by glycolysis with minimal reserve glycolytic
      capacity, whereas nondifferentiated cells generated ATP through oxidative
      phosphorylation. A marked Crabtree effect (acute suppression of respiration by
      addition of glucose, observed in both MC3T3-E1 and calvarial osteoblasts) and
      smaller mitochondrial membrane potential in the differentiated osteoblasts,
      particularly those incubated at high glucose concentrations, indicated a
      suppression of oxidative phosphorylation compared with nondifferentiated
      osteoblasts. In contrast, both nondifferentiated and differentiated 3T3-L1
      adipocytes met ATP demand primarily by oxidative phosphorylation despite a large
      unused reserve glycolytic capacity. In sum, we show that nondifferentiated
      precursor cells prefer to use oxidative phosphorylation to generate ATP; when
      they differentiate to osteoblasts, they gain a strong preference for glycolytic
      ATP generation, but when they differentiate to adipocytes, they retain the strong
      preference for oxidative phosphorylation. Unique metabolic programming in
      mesenchymal progenitor cells may influence cell fate and ultimately determine the
      degree of bone formation and/or the development of marrow adiposity. (c) 2018
      American Society for Bone and Mineral Research.

PMID- 29342318
TI  - Optical Structural Analysis of Individual alpha-Synuclein Oligomers.
AB  - Small aggregates of misfolded proteins play a key role in neurodegenerative
      disorders. Such species have proved difficult to study due to the lack of
      suitable methods capable of resolving these heterogeneous aggregates, which are
      smaller than the optical diffraction limit. We demonstrate here an all-optical
      fluorescence microscopy method to characterise the structure of individual
      protein aggregates based on the fluorescence anisotropy of dyes such as
      thioflavin-T, and show that this technology is capable of studying oligomers in
      human biofluids such as cerebrospinal fluid. We first investigated in vitro the
      structural changes in individual oligomers formed during the aggregation of
      recombinant alpha-synuclein. By studying the diffraction-limited aggregates we
      directly evaluated their structural conversion and correlated this with the
      potential of aggregates to disrupt lipid bilayers. We finally characterised the
      structural features of aggregates present in cerebrospinal fluid of Parkinson's
      disease patients and age-matched healthy controls.

PMID- 29342319
TI  - Validation of The Individualized Neuromuscular Quality of Life in Japanese
      patients with myotonic dystrophy.
AB  - INTRODUCTION: The Individualized Neuromuscular Quality of Life (INQoL) is used to
      measure the quality of life (QoL) of patients with neuromuscular disease. We
      conducted this study to translate and validate the Japanese version of the INQoL
      in patients with myotonic dystrophy. METHODS: Forward and backward translation,
      patient testing, and psychometric validation were performed. We used the 36-Item
      Short Form Health Survey (SF-36) and the modified Rankin scale for concurrent
      validation. RESULTS: The Japanese INQoL was administered to 90 adult patients.
      The coefficients for internal consistency and test-retest reliability were
      adequately high in most domains (Cronbach alpha 0.88-0.96 and intraclass
      coefficient 0.64-0.99). INQoL domains were moderately to strongly associated with
      relevant SF-36 subscales (Spearman's rho -0.23 to -0.74). Symptom severity,
      disease duration, employment status, and use of a ventilator influenced overall
      QoL. DISCUSSION: The INQoL is a reliable and validated measure of QoL for
      Japanese patients with myotonic dystrophy. Muscle Nerve, 2018.

PMID- 29342320
TI  - Association of Pre-ESRD Serum Calcium With Post-ESRD Mortality Among Incident
      ESRD Patients: A Cohort Study.
AB  - Albumin-corrected serum calcium (cSCa) decline at late stages of chronic kidney
      disease and rise after dialysis initiation. Although hypercalcemia is associated
      with higher mortality in end-stage renal disease (ESRD), there are scarce data on
      the impact of pre-ESRD cSCa on post-ESRD mortality. Therefore, we used a large
      national cohort of 21,826 US veterans who transitioned to dialysis in all US
      Department of Veterans Affairs health care facilities over 2009 to 2014 to
      examine the associations with all-cause and cause-specific post-ESRD mortality of
      (1) cSCa concentrations averaged over the last 6 months and (2) its rate of
      decline during the last 12 months before dialysis initiation. Mean concentrations
      and median rate of decline of cSCa were 9.3 +/- 0.7 mg/dL and -0.15
      (interquartile range -0.39 to 0.07) mg/dL/year, respectively. A total of 9596
      patients died during the follow-up period (mean 1.9 years; total 41,541 patient
      years) with an incidence rate of 23.1 per 100 patient-years. There was an
      independent linear association between higher cSCa with higher mortality (ptrend
      < 0.001). The mortality risk associated with cSCa >=9.0 mg/dL was attenuated
      among active vitamin D users (pinteraction < 0.001). Patients with faster decline
      in cSCa showed lower mortality irrespective of baseline cSCa concentrations.
      These cSCa-mortality associations were stronger for noncardiovascular versus
      cardiovascular death. In conclusion, lower pre-ESRD cSCa and faster decline in
      cSCa were consistently and linearly associated with better post-ESRD survival
      among US veterans, especially for noncardiovascular death. Further studies are
      needed to determine if correcting hypocalcemia is beneficial or harmful and which
      intervention is preferred when indicated among patients transitioning to ESRD.
      (c) 2018 American Society for Bone and Mineral Research.

PMID- 29342322
TI  - An Ethenoadenine FAD Analog Accelerates UV Dimer Repair by DNA Photolyase.

PMID- 29342323
TI  - Editorial (2018, Issue 1).

PMID- 29342321
TI  - Contributions of Material Properties and Structure to Increased Bone Fragility
      for a Given Bone Mass in the UCD-T2DM Rat Model of Type 2 Diabetes.
AB  - Adults with type 2 diabetes (T2D) have a higher fracture risk for a given bone
      quantity, but the mechanisms remain unclear. Using a rat model of polygenic obese
      T2D, we demonstrate that diabetes significantly reduces whole-bone strength for a
      given bone mass (MUCT-derived BMC), and we quantify the roles of T2D-induced
      deficits in material properties versus bone structure; ie, geometry and
      microarchitecture. Lumbar vertebrae and ulnae were harvested from 6-month-old
      lean Sprague-Dawley rats, obese Sprague-Dawley rats, and diabetic obese UCD-T2DM
      rats (diabetic for 69 +/- 7 days; blood glucose >200 mg/dL). Both obese rats and
      those with diabetes had reduced whole-bone strength for a given BMC. In obese
      rats, this was attributable to structural deficits, whereas in UCD-T2DM rats,
      this was attributable to structural deficits and to deficits in tissue material
      properties. For the vertebra, deficits in bone structure included thinner and
      more rod-like trabeculae; for the ulnae, these deficits included inefficient
      distribution of bone mass to resist bending. Deficits in ulnar material
      properties in UCD-T2DM rats were associated with increased non-enzymatic
      crosslinking and impaired collagen fibril deformation. Specifically, small-angle
      X-ray scattering revealed that diabetes reduced collagen fibril ultimate strain
      by 40%, and those changes coincided with significant reductions in the elastic,
      yield, and ultimate tensile properties of the bone tissue. Importantly, the
      biomechanical effects of these material property deficits were substantial.
      Prescribing diabetes-specific tissue yield strains in high-resolution finite
      element models reduced whole-bone strength by a similar amount (and in some cases
      a 3.4-fold greater amount) as the structural deficits. These findings provide
      insight into factors that increase bone fragility for a given bone mass in T2D;
      not only does diabetes associate with less biomechanically efficient bone
      structure, but diabetes also reduces tissue ductility by limiting collagen fibril
      deformation, and in doing so, reduces the maximum load capacity of the bone. (c)
      2018 American Society for Bone and Mineral Research.

PMID- 29342324
TI  - Different Atomic Terminations Affect the Photocatalytic Nitrogen Fixation of
      Bismuth Oxybromide: A First Principles Study.
AB  - We have systematically investigated the electronic structures and activation
      capacities of BiOBr {001} facets with different atomic terminations by means of
      DFT methods. Our calculations reveal that oxygen vacancies (OVs) give a
      significant boost in band edges of the O-terminated BiOBr {001} facets, and
      excess electrons induced by OVs could exceed the reduction potentials of high
      energy N2 intermediates. Interestingly, the Bi-terminated BiOBr {001} facets may
      be good candidates for photocatalytic nitrogen fixation due to the stronger
      activation ability of N2 molecules comparing with O-terminated BiOBr {001} facets
      with OVs. Moreover, the Bi-terminated BiOBr {001} facets may tend to yield NH3
      instead of N2 H4 .

PMID- 29342325
TI  - Neuromuscular complications of immune checkpoint inhibitor therapy.
AB  - Immune checkpoint inhibitor (ICPI) therapy unleashes the body's natural immune
      system to fight cancer. ICPIs improve overall cancer survival, however, the
      unbridling of the immune system may induce a variety of immune-related adverse
      events. Neuromuscular immune complications are rare but they can be severe.
      Myasthenia gravis and inflammatory neuropathy are the most common neuromuscular
      adverse events but a variety of others including inflammatory myopathy are
      reported. The pathophysiologic mechanism of these autoimmune disorders may differ
      from that of non-ICPI-related immune diseases. Accordingly, while the optimal
      treatment for ICPI-related neuromuscular disorders generally follows a
      traditional paradigm, there are important novel considerations in selecting
      appropriate immunosuppressive therapy. This review presents 2 new cases, a
      summary of neuromuscular ICPI complications, and an approach to the diagnosis and
      treatment of these disorders. Muscle Nerve, 2018.

PMID- 29342326
TI  - Mixed Fluorotryptophan Substitutions at the Same Residue Expand the Versatility
      of 19 F Protein NMR Spectroscopy.
AB  - The strategy of applying fluorine NMR to characterize ligand binding to a
      membrane protein prepared with mixtures of tryptophans substituted with F at
      different positions on the indole ring was tested. The 19 F NMR behavior of 4-, 5
      , 6-, and 7-fluorotryptophan were directly compared as a function of both
      micellar environment and fragment size for two overlapping apelin receptor
      (AR/APJ) segments; one with a single transmembrane (TM) helix and two tryptophan
      residues, the other with three TM helices and two additional tryptophan residues.
      Chemical shifts, peak patterns, and nuclear spin relaxation rates were observed
      to vary as a function of micellar conditions and F substitution position in the
      indole ring, with the exposure of a given residue to micelle or solvent being the
      primary differentiating factor. Titration of the 3-TM AR segment biosynthetically
      prepared as a mixture of 5- and 7-fluorotryptophan-containing isoforms by two
      distinct peptide ligands (apelin-36 and apela-32) demonstrated site-specific 19 F
      peak intensity changes for one ligand but not the other. In contrast, both
      ligands perturbed 1 H-15 N HSQC peak patterns to a similar degree.
      Characterization of multiple fluorotryptophan types for a given set of tryptophan
      residues, thus, significantly augments the potential to apply 19 F NMR to track
      otherwise obscure modulation of protein conformation and dynamics without an
      explicit requirement for mutagenesis or chemical modification.

PMID- 29342328
TI  - Automated measurement of left ventricular ejection fraction and volume using the
      Philips EPIQ system: Methodological issues on validity and reproducibility.

PMID- 29342329
TI  - When the gold standard is not always golden: The value of invasive hemodynamic
      assessment to overcome the pitfalls of echocardiography in challenging cases of
      mitral stenosis.
AB  - Mitral stenosis is a uncommon valvular lesion in the developed countries.
      Noninvasive evaluation is the first-line modality for assessment of mitral
      stenosis, however the noninvasive methods may have limitations in certain cases.
      Invasive hemodynamics can be used as adjunct tool for assessment of mitral
      stenosis in such difficult cases. Mitral valve using three-dimensional planimetry
      is a promising technique for assessment of mitral stenosis.

PMID- 29342330
TI  - Corrigendum.

PMID- 29342332
TI  - ?

PMID- 29342331
TI  - Reproducibility of automated measurement of left ventricular volumes and ejection
      fraction using the Philips EPIQ system.

PMID- 29342334
TI  - ?

PMID- 29342333
TI  - ?

PMID- 29342335
TI  - ?

PMID- 29342336
TI  - ?

PMID- 29342337
TI  - ?

PMID- 29342339
TI  - ?

PMID- 29342338
TI  - ?

PMID- 29342340
TI  - ?

PMID- 29342341
TI  - Aptamer-Directed Specific Drug Delivery and Magnetic Resonance Imaging of Renal
      Carcinoma Cells In Vitro and In Vivo.
AB  - Magnetic resonance imaging (MRI) with high spatial resolution has been widely
      used in clinics as a noninvasive diagnostic technology, and MRI diagnosis-based
      theranostic nanomaterials have attracted increasing attention. Herein, we report
      on the fabrication of a GO/BSA-Gd2O3/AS1411-DOX theranostic nanocomplex with BSA
      Gd2O3 nanoparticles for use as an MRI contrast agent (CA), with graphene oxide
      (GO) nanoplates as the CA and drug nanocarrier, as well as an aptamer, AS1411, as
      the targeting molecule. The proposed theranostic nanocomplex not only provided
      stronger MR contrast enhancement but also inhibited the growth of 786-0 human
      renal carcinoma cells with the help of the AS1411 aptamer, while sparing the
      normal cells from harm, thus demonstrating their specific drug delivery
      capability. Additionally, 786-0 cells could be specifically recognized using the
      GO/BSA-Gd2O3/AS1411-DOX theranostic nanocomplex with MRI both in vitro and in
      vivo. Notably, most of the nanocomplex that was injected into the tail vein was
      excreted by the kidneys and bladder, while MRI signals from the nanocomplexes
      that accumulated specifically in the tumor region could remain as long as 24
      hours, which is beneficial for future clinical diagnosis and therapy.

PMID- 29342343
TI  - Redox Sensitive Shell and Core Crosslinked Hyaluronic Acid Nanocarriers for Tumor
      Targeted Drug Delivery.
AB  - The purpose of the present study was to develop a robust and redox-sensitive
      nanocarrier based on amphiphilic hyaluronic acid nanoparticles, in which the
      hydrophobic core was crosslinked by photo-crosslinking and the hyaluronic acid
      shell was crosslinked via a bioreducible disulfide linkage. Dynamic light
      scattering showed that the shell and core crosslinked nanocarriers were obviously
      more stable than core crosslinked or non-crosslinked nanoparticles. Moreover, the
      particle size changed as the glutathione concentration was altered, exhibiting
      obvious redox sensitivity. Transmission electron microscopy showed that the
      nanoparticle structure was denser after crosslinking. Additionally, methotrexate
      was effectively encapsulated into nanoparticles with high drug-loading
      efficiency. In vitro methotrexate release assays showed that the methotrexate
      loaded bioreducible hyaluronic acid nanoparticles greatly suppressed drug release
      in phosphate-buffered saline (pH 7.4) without or with 20 MUM glutathione. In
      contrast, in phosphate-buffered saline (pH 7.4) with higher glutathione
      concentrations (2, 5, or 10 mM), methotrexate was released more rapidly and
      completely from the nanocarriers in 24 h. Furthermore, methotrexate was released
      completely and rapidly from the nanoparticles under simulated tumor cell
      conditions (pH 5.0 with 10 mM glutathione), suggesting potential applications in
      tumor-specific drug release. In vitro anticancer activity tests showed that the
      inhibition rate of methotrexate-loaded nanoparticles in HeLa cells reached 94%.
      However, excess hyaluronic acid decreased cell toxicity. Cellular uptake studies
      suggested that the prepared nanoparticles were probably internalized into the
      cancer cells via receptor-mediated endocytosis. Overall, our data demonstrated
      that the bio-reducible shell and core crosslinked nanoparticles could be used as
      a potential carrier for cancer therapy.

PMID- 29342342
TI  - Tranexamic Acid-Encapsulating Thermosensitive Liposomes for Site-Specific
      Pharmaco-Laser Therapy of Port Wine Stains.
AB  - Site-specific pharmaco-laser therapy (SSPLT) is a developmental stage treatment
      modality designed to non-invasively remove superficial vascular pathologies such
      as port wine stains (PWS) by combining conventional laser therapy with the prior
      administration of a prothrombotic and/or antifibrinolytic pharmaceutical
      containing drug delivery system. For the antifibrinolytic SSPLT component, six
      different PEGylated thermosensitive liposomal formulations encapsulating
      tranexamic acid (TA), a potent antifibrinolytic lysine analogue, were
      characterized for drug:lipid ratio, encapsulation efficiency, size, endovesicular
      TA concentration (C TA), phase transition temperature (T m), and assayed for heat
      induced TA release. Assays were developed for the quantification of liposomal TA
      and heat-induced TA release from two candidate formulations. The outcome
      parameters were then combined with a 3D histological reconstruction of a port
      wine stain biopsy to extrapolate in vivo posologies for SSPLT. The prime
      formulation, DPPC:DSPE-PEG2000 (96:4 molar ratio), had a drug:lipid molar ratio
      of 0.82, an encapsulation efficiency of 1.29%, a diameter of 155 nm, and a C TA
      of 214 mM. The peak TA release from this formulation (T m = 42.3  degrees C)
      comprised 96% within 2.5 min, whereas this was 94% in 2 min for DPPC:MPPC:DSPE
      PEG2000 (86:10:4) liposomes (T m = 41.5  degrees C). Computational analysis
      revealed that < 400 DPPC:DSPE-PEG2000 (96:4 molar ratio) liposomes are needed to
      treat a PWS of 40 cm2, compared to a three-fold greater quantity of
      DPPC:MPPC:DSPE-PEG2000 (86:10:4) liposomes, indicating that, in light of the
      assayed parameters and endovascular laser-tissue interactions, the former
      formulation is most suitable for antifibrinolytic SSPLT. This was further
      confirmed with experiments involving ex vivo and in vivo liposome-platelet and
      liposome-red blood cell association as well as uptake and toxicity assays with
      cultured endothelial cells (HUVECs), macrophages (RAW 264.7), and hepatocytes
      (HepG2).

PMID- 29342344
TI  - A Nanoparticle Carrier for Co-Delivery of Gemcitabine and Small Interfering RNA
      in Pancreatic Cancer Therapy.
AB  - BACKGROUND: The concept of precision medicine to treat cancer shows promise and a
      co-delivery carrier for chemotherapy drugs and target genes is the key tool for
      both basic research and clinical application. To address this, we developed a
      cancer-targeting nanoparticle vector to transfer gemcitabine (Gem) and small
      interfering RNA (siRNA) to pancreatic cancer. METHODS: Iron oxide nanoparticles
      (IONPs) resonant at 15 nm were conjugated with the single chain variable fragment
      (scFv) against CD44v6 (scFvCD44v6), which has proven pancreatic cancer-targeting
      specificity as reported in our previous study. Gem was then linked through a
      lysosomally cleavable tetrapeptide linker, resulting in a scFv-targeted
      nanoparticle construct, which was subsequently conjugated to siRNA targeting the
      Bmi-1 oncogene (siBmi-1) to obtain the multifunctional nanoparticle scFv-Gem
      siBmi-1-NPs. A series of biological experiments were performed to test its
      biophysical characterization, gene silencing efficacy and anti-tumor effect in
      vitro and in vivo. RESULTS: The multifunctional nanoparticle not only possesses
      an ultra-small size of approximately 80 nm, excellent biocompatibility and
      biodegradability, but also exerts a synergistic anti-tumor effect both in vitro
      and in vivo, such as inhibition of tumor cell growth, invasion and migration,
      reduction of cell cycle progression and promotion of tumor apoptosis.
      Furthermore, this nanoparticle can efficiently target pancreatic cancer in vivo,
      resulting in the enhanced bioavailability and efficacy of Gem. CONCLUSION: scFv
      Gem-siBmi-1-NPs provide an effective and targeted co-delivery of Gem and siBmi-1
      to pancreatic cancer, and exert an efficient and corporate anti-tumor therapeutic
      effect. This prospective vector shows promise for precise treatment of pancreatic
      cancer.

PMID- 29342345
TI  - Comprehensive Analysis of Secreted Protein, Acidic and Rich in Cysteine in
      Prostate Carcinogenesis: Development of a 3D Nanostructured Bone-Like Model.
AB  - Most aggressive prostate cancer (PCa) types tend to metastasize frequently to
      bone and SPARC, a matricellular protein, might participate in such biological
      processes. The objective of this study was to evaluate the effect of SPARC in
      prostate carcinogenesis and bone metastization. This was explored assessing the
      morphology, metabolic activity and SPARC expression of different PCa cell lines
      resembling different stages of carcinogenesis, using a 3D bone-biomimetic model
      (collagen nanofibers/nanohydroxyapatite) grafted with SPARC. Our findings
      highlight distinct cellular behavior depending on cell type and presence of
      exogenous SPARC. In fact, SPARC addition contributed to the survival and
      significant growth of a non-bone metastatic PCa cell line (LNCaP) on bone-like
      biomaterial. Moreover, SPARC expression levels were evaluated in a series of
      prostatic tissues, comparing normal prostate, pre-neoplastic prostate
      intraepithelial neoplasias and overtly malignant tumors, and also metastasis to
      its correspondent primary prostate tumors, ascertaining potential association
      between SPARC and clinicopathological data. Remarkably, SPARC was overexpressed
      in patients with higher Gleason Score, indicating tumors with poor prognosis, as
      well as in metastasis, particularly from bone sites, compared with their
      respective primary tumors. The results suggest a potential role of SPARC as a
      clinical target on PCa, due to its association with bone metastization.

PMID- 29342346
TI  - Ratiometric Reactive Oxygen Species Nanoprobe for Noninvasive In Vivo Imaging of
      Subcutaneous Inflammation/Infection.
AB  - Release of reactive oxygen species (ROS) accompanied with acute inflammation and
      infection often results in cell death and tissue injury. Several ROS-reactive
      bioluminescent probes have been investigated in recent years to detect ROS
      activity in vivo. Unfortunately, these probes cannot be used to quantify the
      degree of ROS activity and inflammatory responses due to the fact that the extent
      of the bioluminescent signals is also probe-concentration dependent. To address
      this challenge, we fabricated a ratiometric ROS probe in which both ROS-sensitive
      chemiluminescent agents and ROS-insensitive fluorescent reference dye were
      conjugated to particle carriers. The bioluminescence/reference fluorescence
      intensity ratios was calculated to reflect the extent of localized ROS activities
      while circumventing the variations in bioluminescent intensities associated with
      the ROS probe concentrations. The physical and chemical properties of the
      ratiometric probes were characterized. Furthermore, we assessed the accuracy and
      reproducibility of the probe in detecting ROS in vitro. The ability of the
      ratiometric probes to detect ROS production in inflamed/infected tissues was also
      examined using animal models of inflammation and infection. The overall results
      imply that ratiometric ROS probes can rapidly and non-invasively detect and
      quantify the extent of inflammatory responses and bacterial infection on wounds
      in real time.

PMID- 29342347
TI  - A pH-Sensitive Nanosystem Based on Carboxymethyl Chitosan for Tumor-Targeted
      Delivery of Daunorubicin.
AB  - Nanoparticles, such as polymeric micelles, are currently regarded as effective
      drug delivery vehicles. In this study, a series of carboxymethyl
      chitosan/daunorubicin (CMCS/DNR) conjugates with macromolecular carriers of
      different molecular weights (MWs) were prepared and structurally characterized by
      Fourier transform infrared spectroscopy (FT-IR) and 1H-NMR spectroscopy. The
      results indicated that the MWs of the carriers greatly influenced the drug
      loading capacity. DNR was conjugated to the polymer via an acid-sensitive
      hydrazone linkage susceptible to hydrolysis at pH 5-6, thereby enabling
      intracellular DNR release. In aqueous media, the conjugates spontaneously formed
      nano-sized particles with core-shell structures (CMCS and DNR as the shell and
      core, respectively). Dynamic light scattering (DLS) and trans-mission electron
      microscopy (TEM) indicated that the prepared nanoparticles were spherical in
      shape with diameters of 100-200 nm and had a slight negative surface charge. In
      addition, in vitro drug release studies demonstrated that the micelles were
      highly sensitive to mild acidic conditions (pH 5.0) but remained reasonably
      stable at pH 6.5 and pH 7.4. Importantly, cell counting kit-8 (CCK-8) assays
      demonstrated that DNR-conjugated nanoparticles exerted a cytotoxic effect on HeLa
      cells, with the IC50 being approximately 2 times higher than that of free-DNR.
      Furthermore, confocal laser scanning microscopy (CLSM) revealed that the CMCS-hyd
      DNR nanosystem could efficiently deliver and release DNR in the nuclei of cancer
      cells. Taken together, the developed CMCS based pH-sensitive nanosystem may be a
      potential drug delivery vehicle for cancer therapy.

PMID- 29342348
TI  - Characterization of the Uptake Efficiency and Cytotoxicity of Tetrandrine-Loaded
      Poly(N-vinylpyrrolidone)-Block-Poly(epsilon-caprolactone) (PVP-b-PCL)
      Nanoparticles in the A549 Lung Adenocarcinoma Cell Line.
AB  - Tetrandrine (Tet) has been previously reported to induce apoptosis in several
      cancer cell lines. However, poor Tet solubility has limited its further
      application. The lipophilicity of Tet suggests that the development of Tet-loaded
      biodegradable polymeric micelle delivery systems may be possible. In our previous
      work, we demonstrated the superior antitumor efficiency of Tet-loaded mPEG-PCL
      nanoparticles (NPs) in colorectal cancer cell lines. In the present study, we
      report that a spherical core-shell Tet-loaded nanoparticle structure was prepared
      using a nanoprecipitation method by employing amphiphilic poly(N
      vinylpyrrolidone)-block-poly(epsilon-caprolactone) (PVP-b-PCL) copolymers as drug
      carriers. Tet was incorporated into the NPs with high encapsulation efficiency
      and released in a sustained release pattern. Moreover, coumarin-6 (hydrophobic
      fluorescence)-loaded Tet-NP uptake was shown to be mediated mainly by endocytosis
      from the NPs and was more efficient than that of rhodamine B (hydrophilic
      fluorescence)-loaded NP uptake, which was mainly dependent upon infiltration. The
      endocytic uptake process was blocked by NaN3, a mitochondrial inhibitor. In vitro
      studies using the A549 cell line demonstrated the superior cytotoxicity and
      apoptosis induction ability of Tet-NPs in dose- and time-dependent manners
      compared to free Tet. The data obtained from this study, therefore, not only
      confirm the potential use of Tet to treat lung cancer but also suggest an
      effective manner by which to improve the anticancer efficiency of Tet in nano
      drug delivery systems.

PMID- 29342350
TI  - Real-Time Monitoring of Chemical Changes in Three Kinds of Fermented Milk
      Products during Fermentation Using Quantitative Difference Nuclear Magnetic
      Resonance Spectroscopy.
AB  - Fermented milk products are rising in popularity throughout the world as a result
      of their health benefits, including improving digestion, normalizing the function
      of the immune system, and aiding in weight management. This study applies an in
      situ quantitative nuclear magnetic resonance method to monitor chemical changes
      in three kinds of fermented milk products, Bulgarian yogurt, Caspian Sea yogurt,
      and kefir, during fermentation. As a result, the concentration changes in nine
      organic compounds, alpha/beta-lactose, alpha/beta-galactose, lactic acid,
      citrate, ethanol, lecithin, and creatine, were monitored in real time. This
      revealed three distinct metabolic processes in the three fermented milk products.
      Moreover, pH changes were also determined by variations in the chemical shift of
      citric acid during the fermentation processes. These results can be applied to
      estimate microbial metabolism in various flora and help guide the fermentation
      and storage of various fermented milk products to improve their quality, which
      may directly influence human health.

PMID- 29342349
TI  - Membrane Allostery and Unique Hydrophobic Sites Promote Enzyme Substrate
      Specificity.
AB  - We demonstrate that lipidomics coupled with molecular dynamics reveal unique
      phospholipase A2 specificity toward membrane phospholipid substrates. We
      discovered unexpected headgroup and acyl-chain specificity for three major human
      phospholipases A2. The differences between each enzyme's specificity, coupled
      with molecular dynamics-based structural and binding studies, revealed unique
      binding sites and interfacial surface binding moieties for each enzyme that
      explain the observed specificity at a hitherto inaccessible structural level.
      Surprisingly, we discovered that a unique hydrophobic binding site for the
      cleaved fatty acid dominates each enzyme's specificity rather than its catalytic
      residues and polar headgroup binding site. Molecular dynamics simulations
      revealed the optimal phospholipid binding mode leading to a detailed
      understanding of the preference of cytosolic phospholipase A2 for cleavage of
      proinflammatory arachidonic acid, calcium-independent phospholipase A2, which is
      involved in membrane remodeling for cleavage of linoleic acid and for
      antibacterial secreted phospholipase A2 favoring linoleic acid, saturated fatty
      acids, and phosphatidylglycerol.

PMID- 29342351
TI  - Organic Mixed Valence Compounds Derived from Cyclic (Alkyl)(amino)carbenes.
AB  - Readily available room temperature stable organic mixed valence compounds are
      prepared by one-electron reduction of cyclic bis(iminium) salts [derived from
      cyclic (alkyl)(amino)carbenes] bridged by various spacers. These compounds show
      characteristic intervalence charge transfer (IV-CT) bands in the near-infrared
      (NIR). Cyclic voltammetry, EPR, IR, UV-vis, and X-ray studies, as well as DFT
      calculations, show that, depending on the nature of the spacer, these mixed
      valence compounds range from class III to class II.

PMID- 29342353
TI  - Synthesis and Computational Studies Demonstrate the Utility of an Intramolecular
      Styryl Diels-Alder Reaction and Di-t-butylhydroxytoluene Assisted [1,3]-Shift to
      Construct Anticancer dl-Deoxypodophyllotoxin.
AB  - Deoxypodophyllotoxin is a secondary metabolite lignan possessing potent
      anticancer activity with potential as a precursor for known anticancer drugs, but
      its use is limited by scarcity from natural sources. We here report the total
      synthesis of racemic deoxypodophyllotoxin in seven steps using an intramolecular
      styryl Diels-Alder reaction strategy uniquely suited to assemble the
      deoxypodophyllotoxin core. Density functional theory was used to analyze
      concerted, polar, and singlet-open-shell diradical reaction pathways, which
      identified a low-energy concerted [4 + 2] Diels-Alder pathway followed by a
      faster di-t-butylhydroxytoluene assisted [1,3]-formal hydrogen shift.

PMID- 29342354
TI  - A Highly Dynamic Loop of the Pseudomonas aeruginosa PA14 Type IV Pilin Is
      Essential for Pilus Assembly.
AB  - Type IVa pili (T4aP) are long, thin surface filaments involved in attachment,
      motility, biofilm formation, and DNA uptake. They are important virulence factors
      for many bacteria, including Pseudomonas aeruginosa, an opportunistic pathogen
      and common cause of hospital-acquired infections. Each helical filament contains
      thousands of monomers of the major pilin subunit, PilA. Each P. aeruginosa strain
      expresses one of five phylogenetically distinct major pilins, which vary in
      sequence and the nature of their associated accessory protein(s). Here, we
      present the backbone resonance assignment of the C-terminal domain of the group
      III PilA from strain PA14, a highly virulent, globally distributed clone.
      Secondary structure probabilities calculated from chemical shifts were in
      excellent agreement with previous homology modeling using a group V pilin
      structural template. The analysis revealed that the distal segment of the
      alphabeta loop had high microsecond-millisecond dynamics compared with other loop
      regions. Shortening of this segment by internal deletion abrogated pilus assembly
      in a dominant negative manner, suggesting a potential role in pilin
      polymerization. Pilin conformations that support optimal interactions of both the
      conserved hydrophobic N-termini in the pilus core and hydrophilic loops creating
      the filament surface may be necessary to produce stable filaments.

PMID- 29342352
TI  - Chemically Defined Antibody- and Small Molecule-Drug Conjugates for in Vivo Tumor
      Targeting Applications: A Comparative Analysis.
AB  - We present the first direct comparative evaluation of an antibody-drug conjugate
      and of a small molecule-drug conjugate for cancer therapy, using chemically
      defined products which bind with high-affinity to carbonic anhydrase IX, a marker
      of tumor hypoxia and of renal cell carcinoma.

PMID- 29342355
TI  - Convergence of Kirkwood-Buff Integrals of Ideal and Nonideal Aqueous Solutions
      Using Molecular Dynamics Simulations.
AB  - The computation of Kirkwood-Buff integrals (KBIs) using molecular simulations of
      closed systems is challenging due to finite system-size effects. One of the
      problems involves the incorrect asymptotic behavior of the radial distribution
      function. Corrections to rectify such effects have been proposed in the
      literature. This study reports a systematic comparison of the proposed
      corrections (as given by Ganguly et al. J. Chem. Theory Comput. 2013, 9, 1347
      1355 and Kruger et al. J. Phys. Chem. Lett. 2013, 4, 4-7) to assess the
      asymptotic behavior of the RDFs, the KBIs, as well as the estimation of
      thermodynamic quantities for ideal urea-water and nonideal modified-urea-water
      mixtures using molecular dynamics simulations. The results show that applying the
      KBI correction suggested by Kruger et al. on the RDF corrected with the Ganguly
      et al. correction (denoted as B-KBI) yields improved KBI convergence for the
      ideal and nonideal aqueous mixtures. Different averaging regions in the running
      KBIs (correlated or long-range) are assessed, and averaging over the correlated
      region for large system sizes is found to be robust toward the change in the
      degree of solvent nonideality and concentration, providing good estimates of
      thermodynamic quantities. The study provides new insights into improving the KBI
      convergence, the suitability of different averaging regions in KBIs to estimate
      thermodynamic properties, as well as the applicability of correction methods to
      achieve KBI convergence for nonideal aqueous binary mixtures.

PMID- 29342356
TI  - The DARK Side of Total Synthesis: Strategies and Tactics in Psychoactive Drug
      Production.
AB  - Humankind has used and abused psychoactive drugs for millennia. Formally, a
      psychoactive drug is any agent that alters cognition and mood. The term
      "psychotropic drug" is neutral and describes the entire class of substrates,
      licit and illicit, of interest to governmental drug policy. While these drugs are
      prescribed for issues ranging from pain management to anxiety, they are also used
      recreationally. In fact, the current opioid epidemic is the deadliest drug crisis
      in American history. While the topic is highly politicized with racial, gender,
      and socioeconomic elements, there is no denying the toll drug mis- and overuse is
      taking on this country. Overdose, fueled by opioids, is the leading cause of
      death for Americans under 50 years of age, killing ca. 64,000 people in 2016.
      From a chemistry standpoint, the question is in what ways, if any, did organic
      chemists contribute to this problem? In this targeted review, we provide brief
      historical accounts of the main classes of psychoactive drugs and discuss several
      foundational total syntheses that ultimately provide the groundwork for producing
      these molecules in academic, industrial, and clandestine settings.

PMID- 29342357
TI  - Diffusion-Controlled Epitaxy of Large Area Coalesced WSe2 Monolayers on Sapphire.
AB  - A multistep diffusion-mediated process was developed to control the nucleation
      density, size, and lateral growth rate of WSe2 domains on c-plane sapphire for
      the epitaxial growth of large area monolayer films by gas source chemical vapor
      deposition (CVD). The process consists of an initial nucleation step followed by
      an annealing period in H2Se to promote surface diffusion of tungsten-containing
      species to form oriented WSe2 islands with uniform size and controlled density.
      The growth conditions were then adjusted to suppress further nucleation and
      laterally grow the WSe2 islands to form a fully coalesced monolayer film in less
      than 1 h. Postgrowth structural characterization demonstrates that the WSe2
      monolayers are single crystal and epitaxially oriented with respect to the
      sapphire and contain antiphase grain boundaries due to coalescence of 0 degrees 
      and 60 degrees  oriented WSe2 domains. The process also provides fundamental
      insights into the two-dimensional (2D) growth mechanism. For example, the
      evolution of domain size and cluster density with annealing time follows a 2D
      ripening process, enabling an estimate of the tungsten-species surface
      diffusivity. The lateral growth rate of domains was found to be relatively
      independent of substrate temperature over the range of 700-900  degrees C
      suggesting a mass transport limited process, however, the domain shape
      (triangular versus truncated triangular) varied with temperature over this same
      range due to local variations in the Se/W adatom ratio. The results provide an
      important step toward atomic level control of the epitaxial growth of WSe2
      monolayers in a scalable process that is suitable for large area device
      fabrication.

PMID- 29342358
TI  - Synthesis and Biological Characterization of Aryl Uracil Inhibitors of Hepatitis
      C Virus NS5B Polymerase: Discovery of ABT-072, a trans-Stilbene Analog with Good
      Oral Bioavailability.
AB  - ABT-072 is a non-nucleoside HCV NS5B polymerase inhibitor that was discovered as
      part of a program to identify new direct-acting antivirals (DAAs) for the
      treatment of HCV infection. This compound was identified during a medicinal
      chemistry effort to improve on an original lead, inhibitor 1, which we described
      in a previous publication. Replacement of the amide linkage in 1 with a trans
      olefin resulted in improved compound permeability and solubility and provided
      much better pharmacokinetic properties in preclinical species. Replacement of the
      dihydrouracil in 1 with an N-linked uracil provided better potency in the
      genotype 1 replicon assay. Results from phase 1 clinical studies supported once
      daily oral dosing with ABT-072 in HCV infected patients. A phase 2 clinical study
      that combined ABT-072 with the HCV protease inhibitor ABT-450 provided a
      sustained virologic response at 24 weeks after dosing (SVR24) in 10 of 11
      patients who received treatment.

PMID- 29342359
TI  - Semiconducting Photothermal Nanoagonist for Remote-Controlled Specific Cancer
      Therapy.
AB  - Nanomedicine have shown success in cancer therapy, but the pharmacological
      actions of most nanomedicine are often nonspecific to cancer cells because of
      utilization of the therapeutic agents that induce cell apoptosis from inner
      organelles. We herein report the development of semiconducting photothermal
      nanoagonists that can remotely and specifically initiate the apoptosis of cancer
      cells from cell membrane. The organic nanoagonists comprise semiconducting
      polymer nanoparticles (SPNs) and capsaicin (Cap) as the photothermally responsive
      nanocarrier and the agonist for activation of transient receptor potential cation
      channel subfamily V member 1 (TRPV1), respectively. Under multiple NIR laser
      irradiation at the time scale of seconds, the nanoagonists can repeatedly and
      locally release Cap to multiply activate TRPV1 channels on the cellular membrane;
      the cumulative effect is the overinflux of ions in mitochondria followed by the
      induction of cell apoptosis specifically for TRPV1-postive cancer cells. Multiple
      transient activation of TRPV1 channels is essential to induce such a cell death
      both in vitro and in vivo because both free Cap and simple Cap-encapsulated
      nanoparticles fail to do so. The photothermally triggered release also ensures a
      high local concentration of the TRPV1 agonist at tumor site, permitting specific
      cancer cell therapy at a low systemic administration dosage. Our study thus
      demonstrates the first example of ion-channel-specific and remote-controlled drug
      delivery system for cancer cell therapy.

PMID- 29342361
TI  - High-Speed Spectroscopic Transient Absorption Imaging of Defects in Graphene.
AB  - Graphene grain boundaries (GBs) and other nanodefects can deteriorate electronic
      properties. Here, using transient absorption (TA) microscopy we directly
      visualized GBs by TA intensity increase due to change in density of state. We
      also observed a faster decay due to defect-accelerated carrier relaxation in the
      GB area. By line-illumination and parallel detection, we increased the TA
      intensity imaging speed to 1000 frames per second, which is 6 orders of magnitude
      faster than Raman microscopy. Combined with a resonant optical delay tuner which
      scans a 5.3 ps temporal delay within 92 MUs, our system enabled spectroscopic TA
      imaging, at a speed of 50 stacks per second, to probe and characterize graphene
      nanodefects based on the TA decay rate. Finally, we demonstrate real-time
      nondestructive characterization of graphene at a rolling speed of 0.3 m/min,
      which matches the fastest roll-to-roll manufacturing process reported.

PMID- 29342360
TI  - Sustained Delivery of Doxorubicin via Acetalated Dextran Scaffold Prevents
      Glioblastoma Recurrence after Surgical Resection.
AB  - The primary cause of mortality for glioblastoma (GBM) is local tumor recurrence
      following standard-of-care therapies, including surgical resection. With most
      tumors recurring near the site of surgical resection, local delivery of
      chemotherapy at the time of surgery is a promising strategy. Herein drug-loaded
      polymer scaffolds with two distinct degradation profiles were fabricated to
      investigate the effect of local drug delivery rate on GBM recurrence following
      surgical resection. The novel biopolymer, acetalated dextran (Ace-DEX), was
      compared with commercially available polyester, poly(l-lactide) (PLA). Steady
      state doxorubicin (DXR) release from Ace-DEX scaffolds was found to be faster
      when compared with scaffolds composed of PLA, in vitro. This increased drug
      release rate translated to improved therapeutic outcomes in a novel surgical
      model of orthotopic glioblastoma resection and recurrence. Mice treated with DXR
      loaded Ace-DEX scaffolds (Ace-DEX/10DXR) resulted in 57% long-term survival out
      to study completion at 120 days compared with 20% survival following treatment
      with DXR-loaded PLA scaffolds (PLA/10DXR). Additionally, all mice treated with
      PLA/10DXR scaffolds exhibited disease progression by day 38, as defined by a 5
      fold growth in tumor bioluminescent signal. In contrast, 57% of mice treated with
      Ace-DEX/10DXR scaffolds displayed a reduction in tumor burden, with 43%
      exhibiting complete remission. These results underscore the importance of polymer
      choice and drug release rate when evaluating local drug delivery strategies to
      improve prognosis for GBM patients undergoing tumor resection.

PMID- 29342362
TI  - Stereospecific Syntheses of Enaminonitriles and beta-Enaminoesters via Domino
      Ring-Opening Cyclization (DROC) of Activated Cyclopropanes with Pronucleophilic
      Malononitriles.
AB  - Two novel synthetic protocols for the syntheses of highly functionalized five
      membered carbocyclic enaminonitriles and beta-enaminoesters have been developed
      via domino ring-opening cyclization (DROC) and DROC/decarboxylative
      tautomerization of activated cyclopropanes with malononitrile pronucleophiles,
      respectively. Both of the efficient strategies (yield up to 93%) have been
      generalized with various donor-acceptor and acceptor cyclopropanes as well as
      with malononitrile derivatives. The stereospecific variants of the two SN2-type
      DROC strategies have also been developed by employing enantiopure donor-acceptor
      (DA) cyclopropanes to synthesize the corresponding nonracemic products with
      excellent stereoselectivities (dr up to >99:1, ee up to >99%).

PMID- 29342365
TI  - A Standardized Diagnostic Ontology for Fibrotic Interstitial Lung Disease.

PMID- 29342363
TI  - Differential effects of inhibitory G protein isoforms on G protein-gated inwardly
      rectifying K+ currents in adult murine atria.
AB  - G protein-gated inwardly rectifying K+ (GIRK) channels are the major inwardly
      rectifying K+ currents in cardiac atrial myocytes and an important determinant of
      atrial electrophysiology. Inhibitory G protein alpha-subunits can both mediate
      activation via acetylcholine but can also suppress basal currents in the absence
      of agonist. We studied this phenomenon using whole cell patch clamping in murine
      atria from mice with global genetic deletion of Galphai2, combined deletion of
      Galphai1/Galphai3, and littermate controls. We found that mice with deletion of
      Galphai2 had increased basal and agonist-activated currents, particularly in the
      right atria while in contrast those with Galphai1/Galphai3 deletion had reduced
      currents. Mice with global genetic deletion of Galphai2 had decreased action
      potential duration. Tissue preparations of the left atria studied with a
      multielectrode array from Galphai2 knockout mice showed a shorter effective
      refractory period, with no change in conduction velocity, than littermate
      controls. Transcriptional studies revealed increased expression of GIRK channel
      subunit genes in Galphai2 knockout mice. Thus different G protein isoforms have
      differential effects on GIRK channel behavior and paradoxically Galphai2 act to
      increase basal and agonist-activated GIRK currents. Deletion of Galphai2 is
      potentially proarrhythmic in the atria.

PMID- 29342364
TI  - Influence of knee joint position and sex on vastus medialis regional
      architecture.
AB  - Ultrasound imaging was used to investigate vastus medialis (VM) architecture in
      10 males and 10 females at different knee angles. Increase in muscle thickness
      occurs predominantly when the knee angle is changed from 0 degrees  (full
      extension) and 45 degrees  (p < 0.05); increases in VM pennation angle can be
      predominantly observed between 45 degrees  and 90 degrees  (p < 0.05). Sex
      differences in the VM architecture can be observed in the distal (p < 0.01) but
      not in the proximal region of the muscle (p > 0.11).

PMID- 29342366
TI  - Evaluation of the Get Active Questionnaire in community-dwelling older adults.
AB  - Physical activity screening prior to starting a physical activity program is
      important to identify if there are any underlying health conditions. However,
      many older adults do not complete such assessments prior to beginning their
      physical activity program. This project compared the Canadian Society for
      Exercise Physiology's newly developed Get Active Questionnaire (GAQ) to a
      standardized exercise stress test in terms of screening out versus screening in
      false-positive GAQ tests. A convenience sample of community-dwelling adults (male
      n = 58, female n = 54) aged 75 +/- 7 years from London, Ontario, Canada, was
      used. Participants completed a physical exam and physical activity screening
      session (i.e., stress test and GAQ) at a research laboratory that routinely
      conducts community-based referrals. One week after the initial visit,
      participants returned to the study site, completed the GAQ, and were asked
      questions about their perceptions of physical activity screening by a research
      assistant. The GAQ "screened in" participants, but it did not provide the same
      precision of "screening out" at-risk individuals as an exercise stress test; the
      GAQ reduced false-positives versus the stress test, yet there was a large
      proportion of high false-negative results reported. The GAQ shows promise in
      physical activity screening in older adults to engage in exercise safely.
      However, the lack of precision in physical-activity screening out of at-risk
      populations requires further evaluation. Questionnaires such as the GAQ should be
      evaluated in a larger study population at various time points to further assess
      the validity and reliability of physical activity screening tools.

PMID- 29342367
TI  - Cystic Fibrosis Foundation Pulmonary Guidelines. Use of Cystic Fibrosis
      Transmembrane Conductance Regulator Modulator Therapy in Patients with Cystic
      Fibrosis.
AB  - RATIONALE: Cystic fibrosis (CF) transmembrane conductance regulator (CFTR)
      modulators are a new class of medications targeting the underlying defect in CF.
      Ivacaftor (IVA) and IVA combined with lumacaftor (LUM; IVA/LUM) have been
      approved by the U.S. Food and Drug Administration (FDA) for use in patients with
      CF. However, the FDA label for these medications encompasses patient groups that
      were not studied as part of the drug approval process. CF clinicians, patients,
      and their families have recognized a need for recommendations to guide the use of
      these medications. OBJECTIVE: Develop evidence-based guidelines for CFTR
      modulator therapy in patients with CF. METHODS: A multidisciplinary committee of
      CF caregivers and patient representatives was assembled. A methodologist, an
      epidemiologist, a medical librarian, and a biostatistician were recruited to
      assist with the literature search, evidence grading, and generation of
      recommendations. The committee developed clinical questions using the Patient
      Intervention-Comparison-Outcome format. A systematic review was conducted to find
      relevant publications. The evidence was then evaluated using the GRADE (Grading
      of Recommendations, Assessment, Development, and Evaluation) approach, and
      recommendations were made based on this analysis. RESULTS: For adults and
      children aged 6 years and older with CF due to gating mutations other than G551D
      or R117H, the guideline panel made a conditional recommendation for treatment
      with IVA. For those with the R117H mutation, the guideline panel made a
      conditional recommendation for treatment with IVA for 1) adults aged 18 years or
      older, and 2) children aged 6-17 years with a forced expiratory volume in 1
      second (FEV1) less than 90% predicted. For those with the R117H mutation, the
      guideline panel made a conditional recommendation against treatment with IVA for
      1) children aged 12-17 years with an FEV1 greater than 90% predicted, and 2)
      children less than 6 years of age. Among those with two copies of F508del, the
      guideline panel made a strong recommendation for treatment with IVA/LUM for
      adults and children aged 12 years and older with an FEV1 less than 90% predicted;
      and made a conditional recommendation for treatment with IVA/LUM for 1) adults
      and children aged 12 years or older with an FEV1 greater than 90% predicted, and
      2) children aged 6-11 years. CONCLUSIONS: Using the GRADE approach, we have made
      recommendations for the use of CFTR modulators in patients with CF. These
      recommendations will be of help to CF clinicians, patients, and their families in
      guiding decisions regarding use of these medications.

PMID- 29342368
TI  - Reply to Moodley: A Standardized Diagnostic Ontology for Fibrotic Interstitial
      Lung Disease.

PMID- 29342369
TI  - Added Sugar Consumption and Chronic Oral Disease Burden among Adolescents in
      Brazil.
AB  - Chronic oral diseases are rarely studied together, especially with an emphasis on
      their common risk factors. This study examined the association of added sugar
      consumption on "chronic oral disease burden" among adolescents, with
      consideration of obesity and systemic inflammation pathways through structural
      equation modeling. A cross-sectional study was conducted of a complex random
      sample of adolescent students enrolled at public schools in Sao Luis, Brazil ( n
      = 405). The outcome was chronic oral disease burden, a latent variable based on
      the presence of probing depth >=4 mm, bleeding on probing, caries, and clinical
      consequences of untreated caries. The following hypotheses were tested: 1) caries
      and periodontal diseases among adolescents are correlated with each other; 2)
      added sugar consumption and obesity are associated with chronic oral disease
      burden; and 3) chronic oral disease burden is linked to systemic inflammation.
      Models were adjusted for socioeconomic status, added sugar consumption, oral
      hygiene behaviors, obesity, and serum levels of interleukin 6 (IL-6). All
      estimators of the latent variable chronic oral disease burden involved factor
      loadings >=0.5 and P values <0.001, indicating good fit. Added sugar consumption
      (standardized coefficient [SC] = 0.212, P = 0.005), high IL-6 levels (SC = 0.130,
      P = 0.036), and low socioeconomic status (SC = -0.279, P = 0.001) were associated
      with increased chronic oral disease burden values. Obesity was associated with
      high IL-6 levels (SC = 0.232, P = 0.001). Visible plaque index was correlated
      with chronic oral disease burden (SC = 0.381, P < 0.001). Our finding that caries
      and periodontal diseases are associated with each other and with added sugar
      consumption, obesity, and systemic inflammation reinforces the guidance of the
      World Health Organization that any approach intended to prevent noncommunicable
      diseases should be directed toward common risk factors.

PMID- 29342371
TI  - Global-, Regional-, and Country-Level Economic Impacts of Dental Diseases in
      2015.
AB  - Up-to-date information about the economic impact of dental diseases is essential
      for health care decision makers when seeking to make rational use of available
      resources. The purpose of this study was to provide up-to-date estimates for
      dental expenditures (direct costs) and productivity losses (indirect costs) due
      to dental diseases on the global, regional, and country level. Direct costs of
      dental diseases were estimated using a previously established systematic
      approach; indirect costs were estimated using an approach developed by the World
      Health Organization Commission on Macroeconomics and Health and factoring in 2015
      values for gross domestic product and disability-adjusted life years from the
      Global Burden of Disease Study. The estimated direct costs of dental diseases
      amounted to $356.80 billion and indirect costs were estimated at $187.61 billion,
      totaling worldwide costs due to dental diseases of $544.41 billion in 2015. After
      adjustment for purchasing power parity, the highest levels of per capita dental
      expenditures were found for High-Income North America, Australasia, Western
      Europe, High-Income Asia Pacific, and East Asia; the highest levels of per capita
      productivity losses were found for Western Europe, Australasia, High-Income North
      America, High-Income Asia Pacific, and Central Europe. Severe tooth loss was
      found to imply 67% of global productivity losses due to dental diseases, followed
      by severe periodontitis (21%) and untreated caries (12%). From an economic
      perspective, improvements in population oral health may be highly beneficial and
      could contribute to further increases in people's well-being given available
      resources.

PMID- 29342370
TI  - FGF8 Signaling Alters the Osteogenic Cell Fate in the Hard Palate.
AB  - Fibroblast growth factor (FGF) signaling has been implicated in the regulation of
      osteogenesis in both intramembranous and endochondral ossifications. In the
      developing palate, the anterior bony palate forms by direct differentiation of
      cranial neural crest (CNC)-derived mesenchymal cells, but the signals that
      regulate the osteogenic cell fate in the developing palate remain unclear. In the
      present study, we investigated the potential role of FGF signaling in osteogenic
      fate determination of the palatal mesenchymal cells. We showed that locally
      activated FGF8 signaling in the anterior palate using a Shox2Cre knock-in allele
      and an R26RFgf8 allele leads to a unique palatal defect: a complete loss of the
      palatine process of the maxilla as well as formation of ectopic cartilaginous
      tissues in the anterior palate. This aberrant developmental process was
      accompanied by a significantly elevated level of cell proliferation, which
      contributes to an abnormally thickened palatal tissue, where the palatine process
      of the maxilla would normally form, and by a complete inhibition of Osterix
      expression, which accounts for the lack of bone formation. The coexpression of
      Runx2 initially with Sox9 and subsequently with Col II in the ectopic
      cartilaginous tissues indicates a conversion of osteogenic fate to a chondrogenic
      one. Consistent with the unique palatal phenotype, RNA-Sequencing analysis
      revealed that the augmented FGF8 signaling downregulated genes involved in
      ossification, biomineral tissue development, and bone mineralization but
      upregulated genes involved in cell proliferation, cartilage development, and cell
      fate commitment, which was further supported by quantitative real-time reverse
      transcription polymerase chain reaction validation of selected genes. Our results
      demonstrate that FGF8 signaling functions as a negative regulator of osteogenic
      fate and is sufficient to convert a subset of CNC cell-derived mesenchymal cells
      into cartilage in the anterior hard palate, which will have implications in
      future directed differentiation of CNC-derived precursor cells for clinical
      application.

PMID- 29342373
TI  - Errata.

PMID- 29342374
TI  - Errata.

PMID- 29342372
TI  - Enrichment of antibiotic resistance genes in soil receiving composts derived from
      swine manure, yard wastes, or food wastes, and evidence for multiyear persistence
      of swine Clostridium spp.
AB  - The impact of amendment with swine manure compost (SMC), yard waste compost
      (YWC), or food waste compost (FWC) on the abundance of antibiotic resistance
      genes in soil was evaluated. Following a commercial-scale application of the
      composts in a field experiment, soils were sampled periodically for a decade, and
      archived air-dried. Soil DNA was extracted and gene targets quantified by qPCR.
      Compared with untreated control soil, all 3 amendment types increased the
      abundance of gene targets for up to 4 years postapplication. The abundance of
      several gene targets was much higher in soil amended with SMC than in soil
      receiving either YWC or FWC. The gene target ermB remained higher in the SMC
      treatment for a decade postapplication. Clostridia were significantly more
      abundant in the SMC-amended soil throughout the decade following application.
      Eight percent of Clostridium spp. isolates from the SMC treatment carried ermB.
      Overall, addition of organic amendments to soils has the potential to increase
      the abundance of antibiotic resistance genes. Amendments of fecal origin, such as
      SMC, will in addition entrain bacteria carrying antibiotic resistance genes.
      Environmentally recalcitrant clostridia, and the antibiotic resistance genes that
      they carry, will persist for many years under field conditions following the
      application of SMC.

PMID- 29342375
TI  - Errata.

PMID- 29342376
TI  - Countering HIV - Three's the Charm?

PMID- 29342377
TI  - Bivalirudin versus Heparin Monotherapy in Myocardial Infarction.

PMID- 29342378
TI  - In the Balance.

PMID- 29342379
TI  - Elimination of Cost Sharing for Screening Mammography in Medicare Advantage
      Plans.
AB  - BACKGROUND: The Affordable Care Act (ACA) required most insurers and the Medicare
      program to eliminate cost sharing for screening mammography. METHODS: We
      conducted a difference-in-differences study of biennial screening mammography
      among 15,085 women 65 to 74 years of age in 24 Medicare Advantage plans that
      eliminated cost sharing to provide full coverage for screening mammography, as
      compared with 52,035 women in 48 matched control plans that had and maintained
      full coverage. RESULTS: In plans that eliminated cost sharing, adjusted rates of
      biennial screening mammography increased from 59.9% (95% confidence interval
      [CI], 54.9 to 65.0) in the 2-year period before cost-sharing elimination to 65.4%
      (95% CI, 61.8 to 69.0) in the 2-year period thereafter. In control plans, the
      rates of biennial mammography were 73.1% (95% CI, 69.2 to 77.0) and 72.8% (95%
      CI, 69.7 to 76.0) during the same periods, yielding a difference in differences
      of 5.7 percentage points (95% CI, 3.0 to 8.4). The difference in differences was
      9.8 percentage points (95% CI, 4.5 to 15.2) among women living in the areas with
      the highest quartile of educational attainment versus 4.3 percentage points (95%
      CI, 0.2 to 8.4) among women in the lowest quartile. As indicated by the
      difference-in-differences estimates, after the elimination of cost sharing, the
      rate of biennial mammography increased by 6.5 percentage points (95% CI, 3.7 to
      9.4) for white women and 8.4 percentage points (95% CI, 2.5 to 14.4) for black
      women but was almost unchanged for Hispanic women (0.4 percentage points; 95% CI,
      -7.3 to 8.1). CONCLUSIONS: The elimination of cost sharing for screening
      mammography under the ACA was associated with an increase in rates of use of this
      service among older women for whom screening is recommended. The effect was
      attenuated among women living in areas with lower educational attainment and was
      negligible among Hispanic women. (Funded by the National Institute on Aging.).

PMID- 29342380
TI  - E-Cigarettes and the Harm-Reduction Continuum.

PMID- 29342382
TI  - Noninferiority Trials.

PMID- 29342381
TI  - Long-Term Follow-up of Monoclonal Gammopathy of Undetermined Significance.
AB  - BACKGROUND: Monoclonal gammopathy of undetermined significance (MGUS) occurs in
      approximately 3% of persons 50 years of age or older. METHODS: We studied 1384
      patients who were residing in southeastern Minnesota and in whom MGUS was
      diagnosed at the Mayo Clinic in the period from 1960 through 1994; the median
      follow-up was 34.1 years (range, 0.0 to 43.6). The primary end point was
      progression to multiple myeloma or another plasma-cell or lymphoid disorder.
      RESULTS: During 14,130 person-years of follow-up, MGUS progressed in 147 patients
      (11%), a rate that was 6.5 times (95% confidence interval [CI], 5.5 to 7.7) as
      high as the rate in the control population. The risk of progression without
      accounting for death due to competing causes was 10% at 10 years, 18% at 20
      years, 28% at 30 years, 36% at 35 years, and 36% at 40 years. Among patients with
      IgM MGUS, the presence of two adverse risk factors - namely, an abnormal serum
      free light-chain ratio (ratio of kappa to lambda free light chains) and a high
      serum monoclonal protein (M protein) level (>=1.5 g per deciliter) - was
      associated with a risk of progression at 20 years of 55%, as compared with 41%
      among patients who had one adverse risk factor and 19% among patients who had
      neither risk factor. Among patients with non-IgM MGUS, the risk of progression at
      20 years was 30% among those who had the two risk factors, 20% among those who
      had one risk factor, and 7% among those who had neither risk factor. Patients
      with MGUS had shorter survival than was expected in the control population of
      Minnesota residents of matched age and sex (median, 8.1 vs. 12.4 years; P<0.001).
      CONCLUSIONS: Significant differences were noted in the risk of progression
      between patients with IgM MGUS and those with non-IgM MGUS. Overall survival was
      shorter among patients with MGUS than was expected in a matched control
      population. (Funded by the National Cancer Institute.).

PMID- 29342383
TI  - Rib Fracture Associated with Bordetella pertussis Infection.

PMID- 29342384
TI  - Evaluation and Management of Lower-Extremity Ulcers.

PMID- 29342385
TI  - Ovarian Cancer Treatment - Are We Getting Warmer?

PMID- 29342386
TI  - Butterfly Glioma.

PMID- 29342387
TI  - Nudge Units to Improve the Delivery of Health Care.

PMID- 29342388
TI  - Crisis in the Sustainability of the U.S. Blood System.

PMID- 29342389
TI  - A Neglected Epidemic.

PMID- 29342391
TI  - Case 2-2018. A 41-Year-Old Woman with Vision Disturbances and Headache.

PMID- 29342390
TI  - Household-Contact Investigation for Detection of Tuberculosis in Vietnam.
AB  - BACKGROUND: Active case finding is a top priority for the global control of
      tuberculosis, but robust evidence for its effectiveness in high-prevalence
      settings is lacking. We sought to evaluate the effectiveness of household-contact
      investigation, as compared with standard, passive measures alone, in Vietnam.
      METHODS: We performed a cluster-randomized, controlled trial at clinics in 70
      districts (local government areas with an average population of approximately
      500,000 in urban areas and 100,000 in rural areas) in eight provinces of Vietnam.
      Health workers at each district clinic or hospital were assigned to perform
      either household-contact intervention plus standard passive case finding
      (intervention group) or passive case finding alone (control group). In the
      intervention districts, household contacts of patients with positive results for
      tuberculosis on sputum smear microscopy (smear-positive tuberculosis) were
      invited for clinical assessment and chest radiography at baseline and at 6, 12,
      and 24 months. The primary outcome was the cumulative incidence of registered
      cases of tuberculosis among household contacts of patients with tuberculosis
      during a 2-year period. RESULTS: In 70 selected districts, we enrolled 25,707
      household contacts of 10,964 patients who had smear-positive pulmonary
      tuberculosis. In the 36 districts that were included in the intervention group,
      180 of 10,069 contacts were registered as having tuberculosis (1788 cases per
      100,000 population), as compared with 110 of 15,638 contacts (703 per 100,000) in
      the control group (relative risk of the primary outcome in the intervention
      group, 2.5; 95% confidence interval [CI], 2.0 to 3.2; P<0.001); the relative risk
      of smear-positive disease among household contacts in the intervention group was
      6.4 (95% CI, 4.5 to 9.0; P<0.001). CONCLUSIONS: Household-contact investigation
      plus standard passive case finding was more effective than standard passive case
      finding alone for the detection of tuberculosis in a high-prevalence setting at 2
      years. (Funded by the Australian National Health and Medical Research Council;
      ACT2 Australian New Zealand Clinical Trials Registry number, ACTRN12610000600044
      .).

PMID- 29342392
TI  - Toxic Alcohols.

PMID- 29342394
TI  - Identification of Linear and Nonlinear Sensory Processing Circuits from Spiking
      Neuron Data.
AB  - Inferring mathematical models of sensory processing systems directly from input
      output observations, while making the fewest assumptions about the model
      equations and the types of measurements available, is still a major issue in
      computational neuroscience. This letter introduces two new approaches for
      identifying sensory circuit models consisting of linear and nonlinear filters in
      series with spiking neuron models, based only on the sampled analog input to the
      filter and the recorded spike train output of the spiking neuron. For an ideal
      integrate-and-fire neuron model, the first algorithm can identify the spiking
      neuron parameters as well as the structure and parameters of an arbitrary
      nonlinear filter connected to it. The second algorithm can identify the
      parameters of the more general leaky integrate-and-fire spiking neuron model, as
      well as the parameters of an arbitrary linear filter connected to it. Numerical
      studies involving simulated and real experimental recordings are used to
      demonstrate the applicability and evaluate the performance of the proposed
      algorithms.

PMID- 29342395
TI  - Indistinguishable Synapses Lead to Sparse Networks.
AB  - Neurons integrate information from many neighbors when they process information.
      Inputs to a given neuron are thus indistinguishable from one another. Under the
      assumption that neurons maximize their information storage, indistinguishability
      is shown to place a strong constraint on the distribution of strengths between
      neurons. The distribution of individual synapse strengths is found to follow a
      modified Boltzmann distribution with strength proportional to [Formula: see
      text]. The model is shown to be consistent with experimental data from
      Caenorhabditis elegans connectivity and in vivo synaptic strength measurements.
      The [Formula: see text] dependence helps account for the observation of many zero
      or weak connections between neurons or sparsity of the neural network.

PMID- 29342393
TI  - Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer.
AB  - BACKGROUND: Treatment of newly diagnosed advanced-stage ovarian cancer typically
      involves cytoreductive surgery and systemic chemotherapy. We conducted a trial to
      investigate whether the addition of hyperthermic intraperitoneal chemotherapy
      (HIPEC) to interval cytoreductive surgery would improve outcomes among patients
      who were receiving neoadjuvant chemotherapy for stage III epithelial ovarian
      cancer. METHODS: In a multicenter, open-label, phase 3 trial, we randomly
      assigned 245 patients who had at least stable disease after three cycles of
      carboplatin (area under the curve of 5 to 6 mg per milliliter per minute) and
      paclitaxel (175 mg per square meter of body-surface area) to undergo interval
      cytoreductive surgery either with or without administration of HIPEC with
      cisplatin (100 mg per square meter). Randomization was performed at the time of
      surgery in cases in which surgery that would result in no visible disease
      (complete cytoreduction) or surgery after which one or more residual tumors
      measuring 10 mm or less in diameter remain (optimal cytoreduction) was deemed to
      be feasible. Three additional cycles of carboplatin and paclitaxel were
      administered postoperatively. The primary end point was recurrence-free survival.
      Overall survival and the side-effect profile were key secondary end points.
      RESULTS: In the intention-to-treat analysis, events of disease recurrence or
      death occurred in 110 of the 123 patients (89%) who underwent cytoreductive
      surgery without HIPEC (surgery group) and in 99 of the 122 patients (81%) who
      underwent cytoreductive surgery with HIPEC (surgery-plus-HIPEC group) (hazard
      ratio for disease recurrence or death, 0.66; 95% confidence interval [CI], 0.50
      to 0.87; P=0.003). The median recurrence-free survival was 10.7 months in the
      surgery group and 14.2 months in the surgery-plus-HIPEC group. At a median follow
      up of 4.7 years, 76 patients (62%) in the surgery group and 61 patients (50%) in
      the surgery-plus-HIPEC group had died (hazard ratio, 0.67; 95% CI, 0.48 to 0.94;
      P=0.02). The median overall survival was 33.9 months in the surgery group and
      45.7 months in the surgery-plus-HIPEC group. The percentage of patients who had
      adverse events of grade 3 or 4 was similar in the two groups (25% in the surgery
      group and 27% in the surgery-plus-HIPEC group, P=0.76). CONCLUSIONS: Among
      patients with stage III epithelial ovarian cancer, the addition of HIPEC to
      interval cytoreductive surgery resulted in longer recurrence-free survival and
      overall survival than surgery alone and did not result in higher rates of side
      effects. (Funded by the Dutch Cancer Society; ClinicalTrials.gov number,
      NCT00426257 ; EudraCT number, 2006-003466-34 .).

PMID- 29342396
TI  - Cross-Domain Metric and Multiple Kernel Learning Based on Information Theory.
AB  - Learning an appropriate distance metric plays a substantial role in the success
      of many learning machines. Conventional metric learning algorithms have limited
      utility when the training and test samples are drawn from related but different
      domains (i.e., source domain and target domain). In this letter, we propose two
      novel metric learning algorithms for domain adaptation in an information
      theoretic setting, allowing for discriminating power transfer and standard
      learning machine propagation across two domains. In the first one, a cross-domain
      Mahalanobis distance is learned by combining three goals: reducing the
      distribution difference between different domains, preserving the geometry of
      target domain data, and aligning the geometry of source domain data with label
      information. Furthermore, we devote our efforts to solving complex domain
      adaptation problems and go beyond linear cross-domain metric learning by
      extending the first method to a multiple kernel learning framework. A convex
      combination of multiple kernels and a linear transformation are adaptively
      learned in a single optimization, which greatly benefits the exploration of prior
      knowledge and the description of data characteristics. Comprehensive experiments
      in three real-world applications (face recognition, text classification, and
      object categorization) verify that the proposed methods outperform state-of-the
      art metric learning and domain adaptation methods.

PMID- 29342397
TI  - Imaging the Spatiotemporal Dynamics of Cognitive Processes at High Temporal
      Resolution.
AB  - This letter presents a noninvasive imaging technique that captures the exact
      timing and locations of cortical activity sequences that are specific to a
      cognitive process. These precise spatiotemporal sequences can be detected in the
      human brain as specific time-position pattern associated with a cognitive task.
      They are consistent with direct measurements of population activity recorded in
      nonhuman primates, thus suggesting that specific time-position patterns
      associated with a cognitive task can be identified. This imaging technique is
      based on estimating the amplitude of cortical current dipoles from MEG
      recordings. Although the spatial resolution of these estimations is poor
      (approximately 2 cm), the temporal resolution is high (milliseconds). We show
      that within these cortical current dipoles, time points of cortical activation
      can be identified as brief amplitude undulations and that sequences of these
      transients repeat with millisecond accuracy, hence making it possible to treat
      the timing of these transients as point processes. We illustrate the feasibility
      of finding spatiotemporal templates specific to the cognitive processes
      associated with following the rhythm of drumbeats that involve the activation at
      multiple cortical and cerebellar loci. These templates evolve at an accuracy of a
      few milliseconds. This approach can thus pave the way for new perspectives on the
      relationships between brain dynamics and cognition.

PMID- 29342398
TI  - Adaptive Structure Concept Factorization for Multiview Clustering.
AB  - Most existing multiview clustering methods require that graph matrices in
      different views are computed beforehand and that each graph is obtained
      independently. However, this requirement ignores the correlation between multiple
      views. In this letter, we tackle the problem of multiview clustering by jointly
      optimizing the graph matrix to make full use of the data correlation between
      views. With the interview correlation, a concept factorization-based multiview
      clustering method is developed for data integration, and the adaptive method
      correlates the affinity weights of all views. This method differs from
      nonnegative matrix factorization-based clustering methods in that it can be
      applicable to data sets containing negative values. Experiments are conducted to
      demonstrate the effectiveness of the proposed method in comparison with state-of
      the-art approaches in terms of accuracy, normalized mutual information, and
      purity.

PMID- 29342399
TI  - Information-Theoretic Bounds and Approximations in Neural Population Coding.
AB  - While Shannon's mutual information has widespread applications in many
      disciplines, for practical applications it is often difficult to calculate its
      value accurately for high-dimensional variables because of the curse of
      dimensionality. This article focuses on effective approximation methods for
      evaluating mutual information in the context of neural population coding. For
      large but finite neural populations, we derive several information-theoretic
      asymptotic bounds and approximation formulas that remain valid in high
      dimensional spaces. We prove that optimizing the population density distribution
      based on these approximation formulas is a convex optimization problem that
      allows efficient numerical solutions. Numerical simulation results confirmed that
      our asymptotic formulas were highly accurate for approximating mutual information
      for large neural populations. In special cases, the approximation formulas are
      exactly equal to the true mutual information. We also discuss techniques of
      variable transformation and dimensionality reduction to facilitate computation of
      the approximations.

PMID- 29342400
TI  - A Unifying Framework of Synaptic and Intrinsic Plasticity in Neural Populations.
AB  - A neuronal population is a computational unit that receives a multivariate, time
      varying input signal and creates a related multivariate output. These neural
      signals are modeled as stochastic processes that transmit information in real
      time, subject to stochastic noise. In a stationary environment, where the input
      signals can be characterized by constant statistical properties, the systematic
      relationship between its input and output processes determines the computation
      carried out by a population. When these statistical characteristics unexpectedly
      change, the population needs to adapt to its new environment if it is to maintain
      stable operation. Based on the general concept of homeostatic plasticity, we
      propose a simple compositional model of adaptive networks that achieve invariance
      with regard to undesired changes in the statistical properties of their input
      signals and maintain outputs with well-defined joint statistics. To achieve such
      invariance, the network model combines two functionally distinct types of
      plasticity. An abstract stochastic process neuron model implements a generalized
      form of intrinsic plasticity that adapts marginal statistics, relying only on
      mechanisms locally confined within each neuron and operating continuously in
      time, while a simple form of Hebbian synaptic plasticity operates on synaptic
      connections, thus shaping the interrelation between neurons as captured by a
      copula function. The combined effect of both mechanisms allows a neuron
      population to discover invariant representations of its inputs that remain stable
      under a wide range of transformations (e.g., shifting, scaling and (affine
      linear) mixing). The probabilistic model of homeostatic adaptation on a
      population level as presented here allows us to isolate and study the individual
      and the interaction dynamics of both mechanisms of plasticity and could guide the
      future search for computationally beneficial types of adaptation.

PMID- 29342402
TI  - Cutaneous Cryptococcosis Mimicking Leishmaniasis.

PMID- 29342401
TI  - Matched Placental and Circulating Plasmodium falciparum Parasites are Genetically
      Homologous at the var2csa ID1-DBL2X Locus by Deep Sequencing.
AB  - In pregnancy-associated malaria, infected erythrocytes accumulate in the
      placenta. It is unclear if in polyclonal infections this results in distinct
      peripheral and placental parasite populations. We used long amplicon deep
      sequencing of Plasmodium falciparum var2csa ID1-DBL2X from 15 matched peripheral
      and placental samples collected at delivery from a high transmission area to
      determine genetic homology. Despite substantial sequence variation and detecting
      23 haplotypes, the matched pairs mostly contained the same genetic variants, with
      11 pairs sharing 100% of their variants, whereas others showed some
      heterogeneity. Thus, at delivery, peripheral and placental parasites appear to
      intermix and placental genotypes can be inferred through peripheral sampling.

PMID- 29342403
TI  - 18F-FDG PET/CT in the Follow-Up of Mucosal Leishmaniasis.

PMID- 29342404
TI  - Association between Severity of Liver Disease, Frequency of Helicobacter pylori
      Infection, and Degree of Gastric Lesion in Egyptian Patients with Hepatitis B
      Virus Infection.
AB  - The relationship between hepatitis B virus (HBV) infection, severity of liver
      disease, frequency of Helicobacter pylori infection, and degree of gastric
      lesions was not yet fully investigated in Egyptian patients. The present work was
      performed on 100 Egyptian patients with HBV from the National Hepatology and
      Tropical Medicine Institute and 70 healthy volunteers as control group. The
      participants were subjected to full medical history taking, clinical examination,
      and laboratory investigations. All patients were positive for HBV surface antigen
      (HBV sAg), HBV DNA, and negative for hepatitis C virus antibodies. The severity
      of the liver disease was assessed using Child-Pugh scoring system. Screening of
      all participants for H. pylori Ag in stool was performed. Biopsy specimens were
      taken from the gastric lesions of H. pylori-infected patients for
      histopathological examination. The mean age of the patients and control group
      were 34.9 and 33.4 years, respectively. The levels of the liver enzymes were
      statistically higher in HBV patients than the control group. Helicobacter pylori
      Ag in stool was detected in 45.7% of the control group, and a higher percentage
      (60%) was detected in the patients group. Chronic gastritis with glandular
      atrophy and metaplasia was found in 15.6% of patients of Child-Pugh A, 70% of
      Child-Pugh B, and 100% of Child-Pugh C. It could be concluded that the prognosis
      of the liver disease significantly influences the severity of the gastric
      pathology in H. pylori infection.

PMID- 29342405
TI  - Human Laryngeal Infection by Clinostomum complanatum.

PMID- 29342406
TI  - Looking Back at 2017 with ASTMH Past President Patricia Walker: Political
      Challenges Remind Her that "Optimism is a Moral Imperative".

PMID- 29342407
TI  - Vitamin D and iron deficiencies in children and adolescents with cerebral palsy.
AB  - INTRODUCTION: Children and adolescents with cerebral palsy (CP) are at a greater
      risk of malnutrition and micronutrient deficiencies. Two deficiencies that we can
      study and treat are vitaminD (VD) and iron deficiencies; however, no studies have
      described these deficiencies in Chile. OBJECTIVE: To describe the status of VD
      and iron in patients with CP and evaluate the relationship with certain factors
      associated with deficiencies of these micronutrients. PATIENTS AND METHOD: We
      performed a descriptive, cross-sectional study including 69 patients aged between
      2 and 21years, from two public hospitals. Data were obtained on demographic
      variables, motor function, use of feeding tube, and pharmacological treatment. We
      performed a nutritional assessment according to patterns of CP and determined 25
      hydroxyvitaminD (25[OH]D) ferritin, and albumin levels. RESULTS: Patients' mean
      age was 11.1+/-4.9years; 43 (62.3%) were male; and 56 (81.2%) had moderate-to
      severe CP. Thirty-five (50.7%) used a nasogastric tube and/or gastrostomy; 15.4%
      were underweight and 73.8% were eutrophic, all with normal height. Twenty (29%)
      and 4 patients (6.2%) received VD and iron supplementation, respectively.
      Albuminaemia was normal in all patients. Mean 25(OH)D level was 24.3+/-8.8ng/mL;
      33 patients (47.8%) had insufficiency and 21 (30.4%) deficiency; 36 patients
      (52.2%) had low ferritin levels. There was no association between 25(OH)D level
      and the other variables studied. Low ferritin levels were found to be associated
      with older age (P=.03), being male (P=.006), and feeding tube use (P=.006).
      CONCLUSIONS: The patients studied mainly had moderate-to-severe CP, with a high
      frequency of suboptimal VD values and low plasma ferritin; few patients received
      VD and/or iron supplementation. We suggest monitoring 25(OH)D and ferritin levels
      due to the high rate of deficiency of these nutrients; public hospitals should be
      equipped with drugs to treat these deficiencies.

PMID- 29342408
TI  - The role of regulatory RNAs (miRNAs) in asthma.
AB  - INTRODUCTION: Recently, a great deal of attention has been paid to the
      investigation of regulatory functions of microRNA. Currently, many different
      mechanisms involved in the pathogenesis of asthma are known, but the whole
      picture of pathogenesis has not yet been studied. CONCLUSIONS: MicroRNAs play an
      important role in the regulation of many cellular processes. Undoubtedly, these
      regulatory molecules are involved in the pathogenesis of asthma, and therefore
      can be potential targets for treatment.

PMID- 29342409
TI  - Development and characterization of an allergoid of cat dander for immunotherapy.
AB  - BACKGROUND: Allergy to cats is a frequent cause of sensitization to indoor
      allergens and currently there are few alternatives to specific immunotherapy with
      cat native extracts. The objective is to develop and characterize a new allergoid
      to increase the tools available for use in clinical practice. METHODS: The
      allergoid cat dander extract (ACD) was developed from a native cat dander extract
      (NCD) by modification with glutaraldehyde, and the optimal process control was
      determined by SDS-PAGE, DOT BLOT and determination of free amine groups. The ACD
      was characterized in protein profile by SDS-PAGE, size exclusion chromatography
      (SEC) and peptide footprint. The allergenic profile of ACD was determined by
      immunoblot, IgE CAP inhibition and IgG competition ELISA. The major allergen
      content in NCD was obtained by the ELISA sandwich protocol and was extrapolated
      to ACD. RESULTS: The control process determined the optimal development of the
      allergoid. The ACD obtained contains 182.28MUg/mg of protein and 11.90MUg/mg of
      Fel d 1. SDS-PAGE and SEC confirmed the presence of high molecular weight
      proteins in ACD, and the peptide footprint showed the presence of Fel d 1 and Fel
      d 7. The high degree of polymerization was evidenced with the determination of
      the reduction of lysine residues in the allergoid, resulting 91.96%. The ACD
      showed a significant loss of allergenicity respect to NCD, while the IgG-binding
      capacity was maintained. CONCLUSIONS: The ACD obtained presents a good safety
      profile, so would be a good alternative for treatment of cat allergy.

PMID- 29342410
TI  - Palliative non-resective surgery for drug-resistant epilepsy.

PMID- 29342411
TI  - Lumbar tattoos and epidural analgesia in 2018: time to let it go?

PMID- 29342412
TI  - Reply to Christian Seitz's Letter to the Editor 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.

PMID- 29342413
TI  - Rapid detection of blaKPC directly from surveillance rectal swabs by EasyQ KPC.
AB  - The performance of EasyQ KPC assay was evaluated for the first time for blaKPC
      detection directly from surveillance rectal swabs without broth enrichment. Using
      conventional polymerase chain reaction as gold standard method, EasyQ KPC and
      culture-based molecular tests demonstrated a sensitivity/specificity of
      100%/87.3% and 83.3%/98.2%, respectively.

PMID- 29342414
TI  - Bacilli community of saline-alkaline soils from the Ararat Plain (Armenia)
      assessed by molecular and culture-based methods.
AB  - The bacterial community composition in the A horizon of a natural saline-alkaline
      soil located in Ararat Plain (Armenia) was studied using molecular and culture
      based methods The sequence analysis of a 16S rRNA gene clone library and
      denaturing gradient gel electrophoresis (DGGE) profiles indicated dominance of
      Firmicutes populations. The majority of the sequences of the bacterial 16S rRNA
      gene library were close relatives of representatives belonging to the genera
      Halobacillus (41.2%), Piscibacillus (23.5%), Bacillus (23.5%) and Virgibacillus
      (11.8%). Eight novel moderately halophilic bacilli isolates were successfully
      obtained from the enriched cultures of the saline-alkaline soil samples. 16S rRNA
      gene sequence analyses of isolates revealed their affiliation (97.7-99.7%
      similarity) to representatives of the genera Bacillus, Piscibacillus and
      Halobacillus. All isolates were able to tolerate high concentrations of NaCl and
      highly alkaline conditions. This is the first study combining cultivation
      independent and -dependent approaches to reveal the bacterial diversity of the
      saline-alkaline soils of Ararat Plain and it suggested an important role of
      bacilli as key microbes in biogeochemical cycles of these environments.

PMID- 29342415
TI  - Lysosomes-targeting imaging and anticancer properties of novel bis-naphthalimide
      derivatives.
AB  - A series of novel N,N-bis(3-aminopropyl)methylamine bridged bis-naphthalimide
      derivatives NI1-NI8 containing saturated nitrogenous heterocycles were designed
      and synthesized, their cytotoxic activities against Hela, MCF-7, A549 and MGC-803
      cells were investigated, Compounds NI1-NI4 modified with piperidine and
      piperazine exhibited good and selective cytotoxic activity, for instance,
      compounds NI1 and NI4 showed potent cytotoxic activity against Hela cells and MGC
      803 cells with the IC50 values of 2.89, 060, 2.73 and 1.60 MUM, respectively,
      better than the control drug (Amonafide). However, compounds NI5-NI8 conjugated
      with pyrrole derivatives showed weak cytotoxic activities against the all tested
      cell lines. Furthermore, their DNA binding properties, fluorescence imaging and
      cell cycle were investigated. Interestingly, compounds NI1 and NI4 showed
      fluorescence enhancement because of the strong binding with Ct-DNA, and exhibited
      fluorescence imaging with Hela cells on the lysosomes.

PMID- 29342417
TI  - Editor's Choice - A Study of the Cost-effectiveness of Fenestrated/branched EVAR
      Compared with Open Surgery for Patients with Complex Aortic Aneurysms at 2 Years.
AB  - OBJECTIVES: The aim was to assess the cost-effectiveness of fenestrated and
      branched stent grafts (f/b EVAR) compared with open surgical repair (OSR) in
      thoraco-abdominal or complex abdominal aortic aneurysms (TAAA/AAA) at 2 years.
      METHODS: Two matched cohorts of patients with TAAA or complex AAA were compared
      after a follow-up of two years. Patients included in the WINDOW French
      multicentre prospective registry were treated by f/b EVAR, and OSR patients were
      extracted from the French national hospital discharge database. All cause
      mortality was assessed along with readmissions and hospital costs. The
      association between treatment and 2 year mortality was assessed by
      uni/multivariate Cox regression analyses using pre- and post-operative
      characteristics. Incremental cost-effectiveness ratios (ICER) were estimated for
      para/juxtarenal AAA, and infra- and supra-diaphragmatic TAAA. RESULTS: A total of
      268 high risk patients were treated by f/b EVAR and 1678 average or low risk
      patients were treated with OSR during the same period. Mortality did not
      significantly differ between the groups (14.9% vs. 11.8%, p = .150) and
      multivariate Cox regressions did not find an association between 2 year mortality
      and treatment. Similar proportions of patients were readmitted at least once
      (69.7% with f/b EVAR vs. 64.2% with OSR, p = .096) but f/b EVAR patients had more
      readmissions on average (2.2 vs. 1.7, p = .001). Two year hospital costs were
      higher in the f/b EVAR group (?46,039 vs. ?22,779, p < .001). At 2 years, f/b
      EVAR was dominated (more expensive and less effective), except in the supra
      diaphragmatic TAAA subgroup with an ICER of ?42,195,800 per death averted.
      CONCLUSIONS: f/b EVAR in high risk patients offers similar 2 year mortality to
      OSR performed in lower risk patients but at a higher cost. The cost is mainly
      driven by the cost of the stent graft, which is not compensated for by lower
      healthcare resource consumption. Further studies are necessary to evaluate the
      cost-effectiveness in low risk f/b EVAR patients who may experience fewer
      complications.

PMID- 29342418
TI  - Functional characterization of 9 CYP2A13 allelic variants by assessment of
      nicotine C-oxidation and coumarin 7-hydroxylation.
AB  - Cytochrome P450 2A13 (CYP2A13) is responsible for the metabolism of chemical
      compounds such as nicotine, coumarin, and tobacco-specific nitrosamine. Several
      of these compounds have been recognized as procarcinogens activated by CYP2A13.
      We recently showed that CYP2A13*2 contributes to inter-individual variations
      observed in bladder cancer susceptibility because CYP2A13*2 might cause a
      decrease in enzymatic activity. Other CYP2A13 allelic variants may also affect
      cancer susceptibility. In this study, we performed an in vitro analysis of the
      wild-type enzyme (CYP2A13.1) and 8 CYP2A13 allelic variants, using nicotine and
      coumarin as representative CYP2A13 substrates. These CYP2A13 variant proteins
      were heterologously expressed in 293FT cells, and the kinetic parameters of
      nicotine C-oxidation and coumarin 7-hydroxylation were estimated. The quantities
      of CYP2A13 holoenzymes in microsomal fractions extracted from 293FT cells were
      determined by measuring reduced carbon monoxide-difference spectra. The kinetic
      parameters for CYP2A13.3, CYP2A13.4, and CYP2A13.10 could not be determined
      because of low metabolite concentrations. Five other CYP2A13 variants (CYP2A13.2,
      CYP2A13.5, CYP2A13.6, CYP2A13.8, and CYP2A13.9) showed markedly reduced enzymatic
      activity toward both substrates. These findings provide insights into the
      mechanism underlying inter-individual differences observed in genotoxicity and
      cancer susceptibility.

PMID- 29342416
TI  - Identification of novel quinazolinedione derivatives as RORgammat inverse
      agonist.
AB  - Novel small molecules were synthesized and evaluated as retinoic acid receptor
      related orphan receptor-gamma t (RORgammat) inverse agonists for the treatment of
      inflammatory and autoimmune diseases. A hit compound, 1, was discovered by high
      throughput screening of our compound library. The structure-activity relationship
      (SAR) study of compound 1 showed that the introduction of a chlorine group at the
      3-position of 4-cyanophenyl moiety increased the potency and a 3-methylpentane
      1,5-diamide linker is favorable for the activity. The carbazole moiety of 1 was
      also optimized; a quinazolinedione derivative 18i suppressed the increase of IL
      17A mRNA level in the lymph node of a rat model of experimental autoimmune
      encephalomyelitis (EAE) upon oral administration. These results indicate that the
      novel quinazolinedione derivatives have great potential as orally available small
      molecule RORgammat inverse agonists for the treatment of Th17-driven autoimmune
      diseases. A U-shaped bioactive conformation of this chemotype with RORgammat
      protein was also observed.

PMID- 29342419
TI  - Investigation of the transport of xanthine dehydrogenase inhibitors by the urate
      transporter ABCG2.
AB  - Hyperuricemia induces gout and kidney stones and accelerates the progression of
      renal and cardiovascular diseases. Adenosine 5'-triphosphate-binding cassette
      subfamily G member 2 (ABCG2) is a urate transporter, and common dysfunctional
      variants of ABCG2, non-functional Q126X (rs72552713) and semi-functional Q141K
      (rs2231142), are risk factors for hyperuricemia and gout. A recent genome wide
      association study suggested that allopurinol, a serum uric acid-lowering drug
      that inhibits xanthine dehydrogenase, is a potent substrate of ABCG2. In this
      study, we aimed to examine the transport of xanthine dehydrogenase inhibitors via
      ABCG2. Our results show that ABCG2 transports oxypurinol, an active metabolite of
      allopurinol, whereas allopurinol and febuxostat, a new xanthine dehydrogenase
      inhibitor, are not substrates of ABCG2. The amount of oxypurinol transported by
      ABCG2 vesicles significantly increased in the presence of ATP, compared to that
      observed with mock vesicles. Since the half-life of oxypurinol is longer than
      that of allopurinol, the xanthine dehydrogenase-inhibiting effect of allopurinol
      mainly depends on its metabolite, oxypurinol. Our results indicate that the serum
      level of oxypurinol would increase in patients with ABCG2 dysfunction.

PMID- 29342420
TI  - [Use of bronchial blocker in emergent thoracotomy in presence of upper airway
      hemorrhage, and cervical spine fracture: a difficult decision].
AB  - Female, 85 y.o., weighting 60kg, multiple trauma patient. After an initial
      laparotomy, an emergent thoracotomy was performed using a bronchial blocker for
      lung isolation (initial active suction was applied). During surgery, bronchial
      cuff was deflated, causing a self-limited tracheal blood flooding. A second lung
      isolation was attempted but it was not as effective as initially. Probably, a
      lung collapse with the same bronchial blocker was impaired in the second attempt
      because of the obstruction of bronchial blocker lumen by intraoperative
      endobronchial hemorrhage. Bronchial blocker active suction may contribute to
      obtain or accelerate lung collapse, particularly in patients that do not tolerate
      ventilator disconnection technique or lung surgical compression. The use of
      bronchial blockers technology was a valuable alternative to double lumen tubes in
      this case of emergent thoracotomy in the context of a patient having thoracic,
      abdominal trauma, severe laceration of tongue and apophysis odontoid fracture
      associated to massive hemorrhage, despite several pitfalls that could compromise
      its use. The authors intend to discuss the advantages and disadvantages of
      bronchial blockers comparing to double-lumen tubes for lung isolation, and the
      risks of our approach, in this complex multitrauma case.

PMID- 29342421
TI  - The relation between plasma alpha-synuclein level and clinical symptoms or signs
      of Parkinson's disease.
AB  - INTRODUCTION: Parkinson disease (PD) is the common neurodegenerative disease.
      alpha-Synuclein (ASN), main aggregating protein in neural cells of CNS in PD, was
      found in peripheral fluids. Testing ASN in plasma is potential test for diagnose
      PD, but previous studies are controversial. The aim of this study was to
      investigate if plasma ASN level may be a valuable biomarker, is the level of
      plasma ASN concentration different in various motor subtypes of diseases, is
      there a relation between the level of plasma ASN and the severity of motor
      symptoms. METHODS: Patients with PD hospitalized in Neurology Department, Medical
      College were performed sequencing the 8th and 9th exon of GBA gene. Next plasma
      ASN level was tested in 58 patients with sequenced GBA gene and in 38 healthy
      volunteers (HV), matched by the age (respectively 68.43 vs. 64.57 years of age)
      and sex (female %, respectively: 43.10 vs.44.74). Patients were assessed with the
      scales: UPDRS (II, III, IV), Hoehn-Yahr (HY) and qualified to PIGD or TD subtype.
      For homogeneity of the group patients with GBA mutation were excluded from the
      analysis. RESULTS: The ASN level did not differ between patients and HV
      (respectively: 4.53 vs. 3.73ng/ml) and between patients with different subtypes.
      There was inverse correlation between ASN and HY in PIGD subtype. CONCLUSIONS:
      Plasma ASN level is not valuable marker of the disease. It does not differ in
      subtypes of the disease. There is relation between plasma ASN level and the
      severity of the disease in PIGD subtype.

PMID- 29342422
TI  - Magnetic mesoporous molecularly imprinted polymers based on surface precipitation
      polymerization for selective enrichment of triclosan and triclocarban.
AB  - Novel magnetic mesoporous molecularly imprinted polymers (MMIPs) were prepared
      based on surface precipitation polymerization using Triclosan (TCS) as template
      and methacrylic acid as functional monomer. The synthesized MMIPs-TCS were
      applied to the adsorbent of magnetic solid-phase extraction (MSPE) coupled with
      HPLC for the enrichment and determination of TCS. The MMIPs-TCS were
      characterized by fourier-transform infrared spectrometry (FTIR), scanning
      electron microscopy (SEM), transmission electron microscopy (TEM), N2 adsorption
      desorption transmission, and vibrating sample magnetometry. Under the optimum
      condition, the MMIPs-TCS-MSPE-HPLC method shows low limits of detection (LODs)
      (0.20-0.90 MUg L-1) and limits of quantification detection (LOQs) (0.66-2.97 MUg
      L-1), wide linear ranges from 10.0 to 1000 MUg L-1 for each compound with
      exception of 2,4,6-TCP from 20.0 to 1000 MUg L-1, and acceptable reproducibility
      (relative standard deviation, RSD <6.6% for intra-day, RSD <8.1% for inter-day).
      The satisfactory recoveries were in the range of 89.5%-108.4% with good RSDs less
      than 8.0% at the three spiked levels of 20, 50 and 80 MUg L-1. Moreover, the
      adsorption experiments show the MMIPs-TCS possess rapid binding affinity,
      excellent magnetic response, specific selectivity and high adsorption capacity
      toward TCS with a maximum adsorption capacity of 1955.8 MUg g-1.

PMID- 29342423
TI  - Does Bed Rest or Fluid Supplementation Prevent Post-Dural Puncture Headache?

PMID- 29342424
TI  - Corrigendum to "Effect of biochar on the presence of nutrients and ryegrass
      growth in the soil from an abandoned indigenous coking site: The potential role
      of biochar in the revegetation of contaminated site" [Sci. Total Environ. 601-602
      (2017) 469-477].

PMID- 29342425
TI  - Having the patience to allow a resident to operate on your grandmother.

PMID- 29342426
TI  - Coronary transfer during arterial switch-the heart of the matter?

PMID- 29342427
TI  - Reconstructive aortic valve surgery in the elderly: Techniques and outcomes.
AB  - OBJECTIVES: The aim of the study was to evaluate operative techniques and long
      term results after aortic valve or root repair in patients aged 75 years or more.
      METHODS: Between November 2002 and January 2016, a total of 815 patients
      underwent aortic valve or root repair. Among them were 100 patients aged 75 years
      or more (mean, 78 +/- 3; range, 75-88 years), including 17 patients operated on
      an emergency basis because of acute aortic dissection. None/trivial, mild,
      moderate, and severe insufficiency grades were presented in 9, 23, 27, and 41
      patients, respectively. The surgery comprised root repair, cusp repair, and a
      combination of both in 45, 16, and 39 patients, respectively. RESULTS: Early (30
      day) mortality and the rate of permanent neurologic deficit were 2% for each. The
      follow-up was 99% complete, resulting in 427 patient/years. During the follow-up
      period (mean duration, 4.3 +/- 3.2; range, 0.02-11.1 years), only 1 patient
      developed a relevant aortic insufficiency and required aortic valve reoperation.
      There were 24 late deaths, which occurred on average 50.0 +/- 40.6 months (range,
      2.4-135.0) after surgery at the average patient age of 82 +/- 5 years (range, 75
      90). Estimated survival at 5 and 8 years was 76.4% +/- 5.1% and 71.3% +/- 5.9%,
      respectively, and was similar to those of the sex- and age-matched general
      population. CONCLUSIONS: Reconstructive aortic valve surgery is a suitable and
      justifiable surgical option in selected elderly patients undergoing operation by
      surgeons with considerable experience in this kind of surgery. It offers low
      cardiac and valve-related mortality and morbidity, leading to life expectancy
      applicable to the patients' ages.

PMID- 29342428
TI  - Importance of mapping the external environment in image-guided video-assisted
      thoracoscopic surgery.

PMID- 29342429
TI  - Size does really matter.

PMID- 29342430
TI  - Tissue expander-stimulated lengthening of arteries for the treatment of midaortic
      syndrome in children.
AB  - BACKGROUND: Midaortic syndrome (MAS) is a rare condition characterized by
      stenosis of the abdominal aorta. Patients with disease refractory to medical
      management will usually require either endovascular therapy or surgery with use
      of prosthetic graft material for bypass or patch angioplasty. We report our early
      experience with a novel approach using a tissue expander (TE) to lengthen the
      normal native arteries in children with MAS, allowing primary aortic repair
      without the need for prosthetic graft material. METHODS: We conducted a
      retrospective review of patients with MAS undergoing the TE-stimulated
      lengthening of arteries (TESLA) procedure at our institution from 2010 to 2014.
      Data are presented as mean (range). RESULTS: Five patients aged 4.8 years (3-8
      years) underwent the TESLA procedure. Stages of this procedure include the
      following: stage I, insertion of retroaortic TE; stage II, serial TE injections;
      and stage III, final repair with excision of aortic stenosis and primary end-to
      end aortic anastomosis. Stage II was completed in 4 months (1-9 months) with 12
      (7-20) TE injections. Goal lengthening was achieved in all patients. Stage III
      could not be completed in one patient because of extreme aortic inflammation,
      which precluded safe excision of the aortic stenosis and required use of a
      prosthetic bypass graft. The other four patients completed stage III with two
      (one to three) additional vessels also requiring reconstruction (renal or
      mesenteric arteries). At 3.2 years (1-6 years) of follow-up, all patients are
      doing well. CONCLUSIONS: The TESLA procedure allows surgical correction of MAS
      without the need for prosthetic grafts in young children who are still growing.

PMID- 29342431
TI  - Comparison of access type on perioperative outcomes after endovascular aortic
      aneurysm repair.
AB  - OBJECTIVE: Endovascular aneurysm repair (EVAR) can be performed through
      percutaneous or surgical access. Our goal was to assess the difference in
      perioperative outcomes based on access type in a real-world setting. METHODS: The
      Vascular Quality Initiative (VQI) database was queried for EVAR. Univariable
      analysis and multivariable analysis were used to determine the independent effect
      of access type. RESULTS: There were 8340 (64%) and 4747 (36%) EVAR procedures
      performed through percutaneous and surgical access (3395 [72%] transverse and
      1352 [28%] vertical incisions). In 347 cases (4%), percutaneous access failed.
      Percutaneous access was performed more in patients who were younger and male, had
      higher body mass index, were nonsmokers, and had commercial insurance.
      Multivariable analysis showed that surgical transverse compared with percutaneous
      access was associated with more cardiac complications (odds ratio, 1.53; 95%
      confidence interval [CI], 1.14-2.05; P = .005), prolonged operative time (means
      ratio [MR], 1.25; 95% CI, 1.23-1.27; P < .001), larger estimated blood loss (EBL;
      MR, 1.51; 95% CI, 1.45-1.57; P < .001), and length of stay (LOS; MR, 1.28; 95%
      CI, 1.23-1.32; P < .001). Open surgical access through vertical incisions
      compared with percutaneous access was associated with prolonged operative time
      (MR, 1.34; 95% CI, 1.31-1.37; P < .001), larger EBL (MR, 1.67; 95% CI, 1.58-1.77;
      P < .001), and LOS (MR, 1.49; 95% CI, 1.42-1.57; P < .001). Open access through a
      vertical incision compared with a transverse incision was associated with
      prolonged operative time (MR, 1.07; 95% CI, 1.04-1.1; P < .001), larger EBL (MR,
      1.1; 95% CI, 1.04-1.18; P = .001), and LOS (MR, 1.17; 95% CI, 1.1-1.23; P <
      .001). Failed percutaneous access was seen more with previous bypass, ruptured
      aneurysm repair, general anesthesia, female sex, obesity, coronary artery
      disease, and preoperative aspirin use. Failed percutaneous access was associated
      with increased cardiac complications (odds ratio, 2.48; 95% CI, 1.38-4.6; P =
      .003), prolonged operative time (MR, 1.64; 95% CI, 1.56-1.72; P < .001), larger
      EBL (MR, 3.27; 95% CI, 2.95-3.62; P < .001), and longer postoperative LOS (MR,
      1.47; 95% CI, 1.35-1.6; P < .001). There was no independent effect of access type
      on respiratory and lower extremity ischemic complications or mortality.
      CONCLUSIONS: The rate of percutaneous access in this contemporary series is
      higher than historically reported. Percutaneous access is associated with
      decreased operative time, EBL, and LOS and should be considered when possible.
      For open surgical access, transverse incisions are associated with lower
      operative time, EBL, and LOS. Failed percutaneous access is associated with
      higher cardiac complications as well as with operative time, EBL, and LOS. Extra
      caution should be used with patients at high risk for failed percutaneous access.
      Further prospective investigation is needed incorporating details about the
      quality of the access vessel to determine the interactions of these risk factors.

PMID- 29342432
TI  - Pharmacists' scope of practice in travel health: cregulations.
AB  - OBJECTIVES: The primary objective of this study was to assess pharmacists'
      authority to provide travel health services in each state and Washington, DC.
      Secondary objectives were to determine the need for collaborative practice
      agreements (CPAs), protocols, or prescriptions for this type of pharmacy practice
      and to identify jurisdictions where pharmacists are able to practice as travel
      health providers independent of CPAs or individual physician protocols. METHODS:
      An online survey was developed to assess pharmacists' authority to administer
      travel immunizations, furnish travel-related medications, and order travel
      related laboratory tests. Open-ended items on scope of practice, training
      requirements, and pending legislation or regulations were also included. The
      survey was distributed to state pharmacy association executives. A member of the
      research team searched pharmacy laws to clarify missing or inconsistent
      responses. Data were analyzed using descriptive statistics. RESULTS: The survey
      response rate was 76.5% (n = 39). Missing (n = 12) or conflicting (n = 6)
      response issues were resolved. Thus, data were available for 100% of
      jurisdictions. In most jurisdictions, pharmacists were able to provide one or
      more components of this service. In 44 jurisdictions (86.3%), pharmacists were
      allowed to administer travel immunizations. Twenty-seven jurisdictions (52.9%)
      allowed pharmacists to furnish travel medications. Pharmacists in 23
      jurisdictions (43.1%) could order travel health-related laboratory tests.
      Pharmacists can practice independently in 1 state, but CPAs or individual
      physician protocols are required elsewhere. CONCLUSIONS: To the authors'
      knowledge, this study represents the first national pharmacists' travel health
      scope-of-practice analysis. While pharmacists in many jurisdictions can provide
      some components of travel health services, only one, New Mexico, currently allows
      pharmacists to practice all aspects independently. Thus, pharmacists continue to
      have an opportunity to expand scope of practice in travel health. Additional
      research may help to drive increased access to and use of travel health care.

PMID- 29342433
TI  - Applying the oath of a pharmacist to refugee health care.

PMID- 29342434
TI  - Community pharmacists as first responders in Puerto Rico after Hurricane Maria.

PMID- 29342435
TI  - The 2016 American Academy of Ophthalmology IRIS(r) Registry (Intelligent Research
      in Sight) Database: Characteristics and Methods.
AB  - PURPOSE: To describe the characteristics of the patient population included in
      the 2016 IRIS(r) Registry (Intelligent Research in Sight) database for analytic
      aims. DESIGN: Description of a clinical data registry. PARTICIPANTS: The 2016
      IRIS Registry database consists of 17 363 018 unique patients from 7200 United
      States-based ophthalmologists in the United States. METHODS: Electronic health
      record (EHR) data were extracted from the participating practices and placed into
      a clinical database. The approach can be used across dozens of EHR systems. MAIN
      OUTCOME MEASURES: Demographic characteristics. RESULTS: The 2016 IRIS Registry
      database includes data about patient demographics, top-coded disease conditions,
      and visit rates. CONCLUSIONS: The IRIS Registry is a unique, large, real-world
      data set that is available for analytics to provide perspectives and to learn
      about current ophthalmic care and treatment outcomes. The IRIS Registry can be
      used to answer questions about practice patterns, use, disease prevalence,
      clinical outcomes, and the comparative effectiveness of different treatments.
      Limitations of the data are the same limitations associated with EHR data in
      terms of documentation errors or missing data and the lack of images. Currently,
      open access to the database is not available, but there are opportunities for
      researchers to submit proposals for analyses, for example through a Research to
      Prevent Blindness and American Academy of Ophthalmology Award for IRIS Registry
      Research.

PMID- 29342436
TI  - Iris Melanoma Outcomes Based on the American Joint Committee on Cancer
      Classification (Eighth Edition) in 432 Patients.
AB  - PURPOSE: The American Joint Committee on Cancer (AJCC) classification was updated
      to the eighth edition in January 2017, providing staging for iris melanoma. This
      study evaluated outcomes of iris melanoma per the AJCC classification, eighth
      edition. DESIGN: Retrospective case series. PARTICIPANTS: Four hundred thirty-two
      patients with iris melanoma. METHODS: Management including tumor resection,
      plaque radiotherapy, or enucleation. MAIN OUTCOME MEASURES: Local tumor
      recurrence, melanoma-related systemic metastasis, and melanoma-related death.
      RESULTS: Of 432 patients with iris melanoma, AJCC classification was category T1
      (n = 324 [75%]), T2 (n = 83 [19%]), T3 (n = 2 [<1%]), and T4 (n = 23 [5%]). There
      was no difference in age, race, gender, eye, or iris color among T categories.
      Overall, Kaplan-Meier analysis of outcomes (at 5 and 10 years) revealed visual
      acuity reduction by 3 lines or more (42% and 54%, respectively), secondary
      glaucoma (29% and 33%, respectively), local recurrence (8% and 17%,
      respectively), secondary enucleation (12% and 19%, respectively), lymph node
      metastasis (1% and 1%, respectively), melanoma-related systemic metastasis (5%
      and 10%, respectively), and melanoma-related death (3% and 4%, respectively).
      Compared with T1 category, the hazard ratio (HR) for local recurrence in
      nonenucleated eyes was 1.31 for T2, not evaluable (NE) for T3 (because of small
      cohort), and 6.61 for T4; the HR for metastasis was 3.41 for T2, NE for T3
      (because of small cohort), and 25.6 for T4; the HR for death was 7.51 for T2, NE
      for T3 (because of small cohort), and 26.5 for T4; and the odds ratio for
      enucleation was 1.23 for T2, 3.63 for T3, and 4.72 for T4. Features predictive of
      melanoma-related metastasis (multivariate analysis) included secondary glaucoma
      (P < 0.001; HR, 4.51), T2 category (vs. T1; P = 0.01; HR, 4.09), and T4 category
      (vs. T1; P < 0.001; HR, 30.8). Features predictive of melanoma-related death
      (multivariate analysis) included older age (P = 0.008; HR, 2.16 per 10-year
      increase), T2 category (vs. T1; P = 0.005; HR, 8.07), and T4 category (vs. T1; P
      < 0.001; HR, 20.3). CONCLUSIONS: The AJCC eighth edition classification provides
      prognostic stratification of iris melanoma. By multivariate analysis, the ratio
      for melanoma-related metastasis was 4 times greater in category T2 and 31 times
      greater in T4 compared with T1. The ratio for melanoma-related death was 8 times
      greater in category T2 and 20 times greater in T4 compared with T1. The cohort
      size for T3 was too small to provide useful information.

PMID- 29342437
TI  - Performance Rates Measured in the American Academy of Ophthalmology IRIS(c)
      Registry (Intelligent Research in Sight).

PMID- 29342438
TI  - Vitreoretinal Complications and Outcomes in 92 Eyes Undergoing Surgery for
      Modified Osteo-Odonto-Keratoprosthesis: A 10-Year Review.
AB  - PURPOSE: To analyze vitreoretinal (VR) complications and treatment outcomes in
      eyes undergoing modified osteo-odonto-keratoprosthesis (OOKP) surgery. DESIGN:
      Retrospective case series. PARTICIPANTS: All patients who underwent modified OOKP
      (mOOKP) surgery at a tertiary eye-care center from March 2003 to February 2013
      were included. METHODS: Medical records were reviewed for relevant medical
      history, best-corrected visual acuity (BCVA), slit-lamp examination, ultrasound
      scan, oral examination findings, and VR complications. MAIN OUTCOME MEASURES: The
      BCVA at the last visit. Optimal anatomic outcome was attached retina with a
      normal intraocular pressure at the last visit. RESULTS: A total of 92 eyes of 90
      patients were included. Indications for OOKP included Stevens-Johnson syndrome (n
      = 53), chemical injury (n = 36), and ocular cicatricial pemphigoid (n = 3). A
      total of 41 eyes of 39 patients developed VR complications, including vitritis (n
      = 21), retinal detachment (RD) (n = 12; primary RD = 5), retroprosthetic membrane
      (RPM) (n = 10; primary RPM = 2), endophthalmitis (n = 8), vitreous hemorrhage
      (VH) (n = 5; primary VH = 1), serous choroidal detachment (n = 5), hemorrhagic
      choroidal detachment (n = 2), and leak-related hypotony (n = 1). Mean interval
      from mOOKP surgery to occurrence of VR complication(s) was 43.8 months (median,
      41.9 months; range, 0.2-95.5 months). After treatment of VR complication, visual
      improvement was seen in 17 eyes (42%) (mean improvement = 1.2 logarithm of the
      minimum angle of resolution [logMAR]; median, 0.8 logMAR; range, 0.1-2.5 logMAR),
      visual decline in 7 eyes (14%) (mean decline in BCVA = 0.6 logMAR; median, 0.4
      logMAR; range, 0.3-1.8 logMAR), and no change in BCVA in 17 eyes (42%). However,
      BCVA >=6/60 was retained in 19 eyes and >=6/18 was retained in 9 eyes after final
      VR treatment. CONCLUSIONS: Vitreoretinal complications constitute a significant
      cause of visual morbidity in eyes undergoing mOOKP surgery and pose a challenging
      situation to manage. However, appropriate and timely intervention can achieve
      encouraging results.

PMID- 29342439
TI  - Review of Ophthalmology Medical Professional Liability Claims in the United
      States from 2006 through 2015.
AB  - PURPOSE: To describe characteristics of closed medical professional liability
      (MPL) claims against ophthalmologists in the United States. DESIGN: Retrospective
      analysis of MPL claims from 2006-2015. Data were obtained from the Physician
      Insurers Association of America (PIAA) Data Sharing Project (DSP). Comparison was
      made between ophthalmology and all healthcare specialties for physician
      demographics, prevalence and costs associated with closed claims, and resolution
      of claims. The most prevalent chief medical factor, presenting medical condition,
      operative procedure, outcomes, and resolution of ophthalmology claims were
      compared between the 2006-2010 and 2011-2015 periods. PARTICIPANTS: From 2006
      2015, 90 743 MPL claims were closed: 2.6% (2325/90 743) of closed claims and 2.2%
      (564/24 670) of all paid claims were against ophthalmologists. METHODS:
      Retrospective analysis of MPL claims captured by the PIAA DSP over a 10-year
      period. MAIN OUTCOME MEASURES: Subspecialty pertaining to the claim, number of
      claims closed and paid, indemnity paid, allocated loss adjustment expenses, chief
      medical factor, presenting medical condition, operative procedure, outcome, and
      resolution. RESULTS: Only 24% of closed claims against ophthalmologists resulted
      in payment. Two-thirds were dropped, withdrawn, or dismissed. Ninety percent of
      claims that received a verdict were favorable toward the ophthalmologist.
      Cataract and cornea surgeries were the most prevalent and most costly operative
      procedures, accounting for 50% of all claims and $47 641 376 and $32 570 148 in
      total paid indemnity, respectively. Average indemnity was higher for corneal
      procedures ($304 476) than vitreoretinal procedures ($270 141) or oculoplastic
      procedures on the eyelid ($222 471) or orbit and eyeball ($183 467). The
      prevalence and cost of claims related to endophthalmitis declined from 2006-2010
      (n = 38/1160 [3.3%]; average indemnity, $516 875) period to the 2011-2015 (n =
      26/1165 [2.2%]; average indemnity, $247 083) period. Average indemnity paid ($280
      227 vs. $335 578) and amount spent on legal defense ($41 450 vs. $46 391) was
      slightly lower among ophthalmologists compared with all healthcare specialties,
      respectively. CONCLUSIONS: Ophthalmology has a relatively low number of
      malpractice claims reported compared with other healthcare specialties and shows
      less spending on average indemnity and defense. Further studies are needed to
      investigate the reasons for the higher prevalence of claims related to cataract
      and corneal surgeries and the higher average indemnity paid for corneal
      procedures relative to vitreoretinal or oculoplastic procedures.

PMID- 29342440
TI  - The critical warning sign of real-time brainstem auditory evoked potentials
      during microvascular decompression for hemifacial spasm.
AB  - OBJECTIVE: The aim of this study was to define the critical warning sign of real
      time brainstem auditory evoked potential (BAEP) for predicting hearing loss (HL)
      after microvascular decompression (MVD) for hemifacial spasm (HFS). METHODS: Nine
      hundred and thirty-two patients with HFS who underwent MVD with intraoperative
      monitoring (IOM) of BAEP were analyzed. We used a 43.9 Hz/s stimulation rate and
      400 averaging trials to obtain BAEP. To evaluate HL, pure-tone audiometry and
      speech discrimination scoring were performed before and one week after surgery.
      We analyzed the incidence for postoperative HL according to BAEP changes and
      calculated the diagnostic accuracy of significant warning criteria. RESULTS: Only
      11 (1.2%) patients experienced postoperative HL. The group showing permanent loss
      of wave V showed the largest percentage of postoperative HL (p < 0.001). No
      patient who experienced only latency prolongation (>=1 ms) had postoperative HL.
      Loss of wave V and latency prolongation (>=1 ms) with amplitude decrement (>=50%)
      were highly associated with postoperative HL. CONCLUSIONS: Loss of wave V and
      latency prolongation of 1 ms with amplitude decrement >=50% were the critical
      warning signs of BAEP for predicting postoperative HL. SIGNIFICANCE: These
      findings elucidate the critical warning sign of real-time BAEP.

PMID- 29342441
TI  - Improving Professionalism Between Radiology and Emergency Medicine.

PMID- 29342442
TI  - HIV-related Refractory Hodgkin Lymphoma: A Case Report of Complete Response to
      Nivolumab.

PMID- 29342443
TI  - Test-retest reliability of transcranial magnetic stimulation EEG evoked
      potentials.
AB  - BACKGROUND: Transcranial magnetic stimulation (TMS)-evoked potentials (TEPs),
      recorded using electroencephalography (TMS-EEG), offer a powerful tool for
      measuring causal interactions in the human brain. However, the test-retest
      reliability of TEPs, critical to their use in clinical biomarker and
      interventional studies, remains poorly understood. OBJECTIVE/HYPOTHESIS: We
      quantified TEP reliability to: (i) determine the minimal TEP amplitude change
      which significantly exceeds that associated with simply re-testing, (ii) locate
      the most reliable scalp regions of interest (ROIs) and TEP peaks, and (iii)
      determine the minimal number of TEP pulses for achieving reliability. METHODS:
      TEPs resulting from stimulation of the left dorsolateral prefrontal cortex were
      collected on two separate days in sixteen healthy participants. TEP peak
      amplitudes were compared between alternating trials, split-halves of the same
      run, two runs five minutes apart and two runs on separate days. Reliability was
      quantified using concordance correlation coefficient (CCC) and smallest
      detectable change (SDC). RESULTS: Substantial concordance was achieved in
      prefrontal electrodes at 40 and 60 ms, centroparietal and left parietal ROIs at
      100 ms, and central electrodes at 200 ms. Minimum SDC was found in the same
      regions and peaks, particularly for the peaks at 100 and 200 ms. CCC, but not
      SDC, reached optimal values by 60-100 pulses per run with saturation beyond this
      number, while SDC continued to improve with increased pulse numbers. CONCLUSION:
      TEPs were robust and reliable, requiring a relatively small number of trials to
      achieve stability, and are thus well suited as outcomes in clinical biomarker or
      interventional studies.

PMID- 29342445
TI  - Case report of an uncommon case of drain-site hernia after colorectal surgery.
AB  - BACKGROUND: trocar site herniation is a rare but potentially serious complication
      of laparoscopic surgery. Data about drain site hernia after laparoscopic surgery
      is scarce and anecdotal. CASE PRESENTATION: we report an uncommon case of drain
      site hernia in a man undergone laparoscopic left colectomy for a colonic
      adenocarcinoma who developed small bowel herniation in a 10 mm port site, in
      which a 24 FR drain was inserted leaving a real free space of 2 mm. DISCUSSION:
      laparoscopic approach has gained widespread acceptance in each surgical fields
      because of the perceived better postoperative outcomes in terms of less pain,
      faster recovery, and lower risk of incisional hernia. However, the risk of trocar
      site hernia has been known since 1967. Different risk factors for the development
      of trocar site hernia are described in literature: the trocar diameter and
      design, preexisting fascial defects, enlargement of a port site to remove a
      specimen, high blood glucose levels, obesity, increase intra-abdominal pressure
      as in chronic obstructive airway disease or extensive manipulation of the trocar
      during surgical intervention, which may enlarge the trocar site and thus induce
      small bowel herniation. However, the most important recognized risk factor for
      trocar site hernia is the size of the trocar. CONCLUSIONS: waiting for further
      studies, the lesson to be learnt from this case report is that, even if the free
      space after drain positioning is minimal, drain should not be positioned through
      the 10 mm trocar to allow the closure of fascial defect in order to avoid any
      herniation.

PMID- 29342444
TI  - Scarlet Fever Epidemic in China Caused by Streptococcus pyogenes Serotype M12:
      Epidemiologic and Molecular Analysis.
AB  - From 2011, Hong Kong and mainland China have witnessed a sharp increase in
      reported cases, with subsequent reports of epidemic scarlet fever in North Asia
      and the United Kingdom. Here we examine epidemiological data and investigate the
      genomic context of the predominantly serotype M12 Streptococcus pyogenes scarlet
      fever isolates from mainland China. Incident case data was obtained from the
      Chinese Nationwide Notifiable Infectious Diseases Reporting Information System.
      The relative risk of scarlet fever in recent outbreak years 2011-2016 was
      calculated using the median age-standardised incidence rate, compared to years
      2003-2010 prior this outbreak. Whole genome sequencing was performed on 32 emm12
      scarlet fever isolates and 13 emm12 non-scarlet fever isolates collected from
      different geographic regions of China, and compared with 203 published emm12 S.
      pyogenes genomes predominantly from scarlet fever outbreaks in Hong Kong (n=134)
      and the United Kingdom (n=63). We found during the outbreak period (2011-2016),
      the median age-standardised incidence in China was 4.14/100,000 (95% confidence
      interval (CI) 4.11-4.18), 2.62-fold higher (95% CI 2.57-2.66) than that of
      1.58/100,000 (95% CI 1.56-1.61) during the baseline period prior to the outbreak
      (2003-2010). Highest incidence was reported for children 5years of age
      (80.5/100,000). Streptococcal toxin encoding prophage phiHKU.vir and phiHKU.ssa
      in addition to the macrolide and tetracycline resistant ICE-emm12 and ICE-HKU397
      elements were found amongst mainland China multi-clonal emm12 isolates suggesting
      a role in selection and expansion of scarlet fever lineages in China. Global
      dissemination of toxin encoded prophage has played a role in the expansion of
      scarlet fever emm12 clones. These findings emphasize the role of comprehensive
      surveillance approaches for monitoring of epidemic human disease.

PMID- 29342446
TI  - The impact of happy and angry faces on working memory in depressed adolescents.
AB  - Recent cognitive models suggest that the ability to control emotional information
      in working memory (WM) may be implicated in the etiology and maintenance of
      depression. However, few studies have examined the effects of processing relevant
      and irrelevant emotional stimuli on WM performance in depressed adolescents. In
      the current study, depressed adolescents (n = 27) and healthy adolescents (n =
      49) completed two versions of an emotional n-back task: a low WM load (0-back)
      task and a high WM load (2-back) task. In the emotion-relevant condition
      participants were asked to attend to the emotional expression of an angry, happy,
      or neutral face, whereas in the emotion-irrelevant condition participants were
      asked to attend to the gender of the face. The results showed a WM improvement
      for happy faces in the emotion-relevant condition and a WM impairment for happy
      faces in the emotion-irrelevant condition for healthy adolescents but not for
      depressed adolescents. No biases toward angry faces were found. These results
      demonstrate that depressed adolescents do not show a preferential processing of
      angry faces but rather fail to show a positivity bias as seen in healthy
      adolescents. This supports the theoretical notion that a depressive disorder is
      characterized by a blunted reactivity toward positive information and may provide
      new insights into the underlying mechanisms of youth depression.

PMID- 29342447
TI  - Design, synthesis and anticancer studies of novel aminobenzazolyl pyrimidines as
      tyrosine kinase inhibitors.
AB  - Abnormal signalling from the Protein tyrosine kinases (PTKs) like receptor
      tyrosine kinases and intracellular tyrosine kinases can lead to diseases such as
      cancer especially non-small cell lung cancer, chronic myeloid leukaemia and
      gastrointestinal stromal tumours. Various Protein tyrosine kinase inhibitors are
      available but face poor bioavailability, severe toxicities and recent cases of
      drug-resistant cancers prompts for development of better drug molecules. In this
      study we report the design and development of a novel Protein Tyrosine Kinase
      (PTK) inhibitor on the basis of pharmacophore modelling. Compound 2
      (benzo[d]oxazol-2-ylamino)-N-(2-chloro-4-fluorophenyl)-4-methyl-6-(3-nitrophenyl)
      pyrimidine-5-carboxamide 31 was obtained containing essential pharmacophore
      structural features. This compound exhibited highest activity against leukaemia
      cell line (RPMI-8226) at 0.7244 uM, renal cancer cell line (A498) at 0.8511 uM
      and prostate cancer cell line (PC-3) at 0.7932 uM on the NCI five dose assay
      test. The PTK assay provides promising activity at IC50 of 0.07 uM in the human
      breast cancer cell line MDA-MB-468. Compound 31 had good intermolecular
      interaction with PTK in the molecular docking studies, this ligand-enzyme complex
      was found to stable in the MM-PBSA study over 100 ns. It had 54.22% oral
      bioavailability with Tmax of 0.60 h which is higher compared to the dasatinib
      with bioavailability and Tmax of 14-34% and 1-1.42 h respectively. Anticancer
      action of 31 was found to be impressive in pharmacokinetic studies making it a
      potential lead molecule.

PMID- 29342448
TI  - Generation of induced pluripotent stem cell line, CSSi002-A (2851), from a
      patient with juvenile Huntington Disease.
AB  - Huntington Disease (HD) is an autosomal dominant disorder characterized by motor,
      cognitive and behavioral features caused by a CAG expansion in the HTT gene
      beyond 35 repeats. The juvenile form (JHD) may begin before the age of 20years
      and is associated with expanded alleles as long as 60 or more CAG repeats. In
      this study, induced pluripotent stem cells were generated from skin fibroblasts
      of a 8-year-old child carrying a large size mutation of 84 CAG repeats in the HTT
      gene. HD appeared at age 3 with mixed psychiatric (i.e. autistic spectrum
      disorder) and motor (i.e. dystonia) manifestations.

PMID- 29342449
TI  - Increased Use of Adrenaline in the Management of Childhood Anaphylaxis Over the
      Last Decade.
AB  - BACKGROUND: We recently determined that allergy training programs have improved
      physician recognition and diagnosis of pediatric anaphylaxis in the last decade.
      OBJECTIVE: To investigate for changes in management, in particular the
      appropriate use of adrenaline for the treatment of anaphylaxis in a tertiary
      pediatric emergency department (PED). METHODS: We conducted a retrospective case
      note study including children aged 0 to 16 years coded and verified for
      anaphylaxis comparing cases in years 2003/2004 with 2012. This included
      standardized information on clinical presentation, demographic characteristics,
      vital signs, mode of transport, and management of anaphylaxis including the use
      of adrenaline and/or adjunct therapy. Follow-up management plans were also
      recorded. RESULTS: In 2003/2004, a total of 92 cases were coded and verified for
      anaphylaxis from 83,832 PED presentations compared with 159 cases from 71,822 PED
      presentations in 2012. A significantly higher proportion of cases were
      appropriately managed with adrenaline in 2012 compared with 2003/2004, when
      intensive training programs had not yet been introduced (P = .03). Vital signs
      were more frequently documented in 2012 (P < .001) than in 2003/2004, and there
      was significantly less administration of other medications (corticosteroids,
      bronchodilators, and antihistamines) (P < .05). Also, changes in discharge
      management occurred with an improved dispensing/prescription of adrenaline
      autoinjectors and more frequent follow-up arrangement with specialist allergy
      services (P < .001). CONCLUSIONS: There was a significant improvement in the
      management of anaphylaxis over this 10-year period. This change was observed
      after the introduction of intensified physician training programs in which
      anaphylaxis management was a key component highlighting the importance of
      cooperation between pediatric emergency and allergy services.

PMID- 29342450
TI  - Occupational allergic respiratory disease (rinoconjunctivitis and asthma) in a
      cheese factory worker.

PMID- 29342451
TI  - Decadal Changes in the Edible Supply of Seafood and Methylmercury Exposure in the
      United States.
AB  - BACKGROUND: Methylmercury (MeHg) exposure is associated with adverse effects on
      neurodevelopment and cardiovascular health. Previous work indicates most MeHg is
      from marine fish sold in the commercial market, but does not fully resolve supply
      regions globally. This information is critical for linking changes in
      environmental MeHg levels to human exposure in the U.S. population. OBJECTIVES:
      We used available data to estimate the geographic origins of seafood consumed in
      the United States (major ocean basins, coastal fisheries, aquaculture,
      freshwater) and how shifts in edible supply affected MeHg exposures between 2000
      2002 and 2010-2012. METHODS: Source regions for edible seafood and MeHg exposure
      in the United States were characterized from national and international landing,
      export and import data from the Food and Agricultural Organization of the United
      Nations and the U.S. National Marine Fisheries Service. RESULTS: Our analysis
      suggests 37% of U.S. population-wide MeHg exposure is from mainly domestic
      coastal systems and 45% from open ocean ecosystems. We estimate that the Pacific
      Ocean alone supplies more than half of total MeHg exposure. Aquaculture and
      freshwater fisheries together account for an estimated 18% of total MeHg intake.
      Shifts in seafood types and supply regions between 2000-2002 and 2010-2012
      reflect changes in consumer preferences (e.g., away from canned light meat tuna),
      global ecosystem shifts (e.g., northern migration of cod stocks), and increasing
      supply from aquaculture (e.g., shrimp and salmon). CONCLUSION: Our findings
      indicate global actions that reduce anthropogenic Hg emissions will be beneficial
      for U.S. seafood consumers because open ocean ecosystems supply a large fraction
      of their MeHg exposure. However, our estimates suggest that domestic actions can
      provide the greatest benefit for coastal seafood consumers.
      https://doi.org/10.1289/EHP2644.

PMID- 29342452
TI  - Estimated Effect of Temperature on Years of Life Lost: A Retrospective Time
      Series Study of Low-, Middle-, and High-Income Regions.
AB  - BACKGROUND: Numerous studies have reported a strong association between
      temperature and mortality. Additional insights can be gained from investigating
      the effects of temperature on years of life lost (YLL), considering the life
      expectancy at the time of death. OBJECTIVES: The goal of this work was to assess
      the association between temperature and YLL at seven low-, middle-, and high
      income sites. METHODS: We obtained meteorological and population data for at
      least nine years from four Health and Demographic Surveillance Sites in Kenya
      (western Kenya, Nairobi), Burkina Faso (Nouna), and India (Vadu), as well as data
      from cities in the United States (Philadelphia, Phoenix) and Sweden (Stockholm).
      A distributed lag nonlinear model was used to estimate the association of daily
      maximum temperature and daily YLL, lagged 0-14 d. The reference value was set for
      each site at the temperature with the lowest YLL. RESULTS: Generally, YLL
      increased with higher temperature, starting day 0. In Nouna, the hottest
      location, with a minimum YLL temperature at the first percentile, YLL increased
      consistently with higher temperatures. In Vadu, YLL increased in association with
      heat, whereas in Nairobi, YLL increased in association with both low and high
      temperatures. Associations with cold and heat were evident for Phoenix (stronger
      for heat), Stockholm, and Philadelphia (both stronger for cold). Patterns of
      associations with mortality were generally similar to those with YLL.
      CONCLUSIONS: Both high and low temperatures are associated with YLL in high-,
      middle-, and low-income countries. Policy guidance and health adaptation measures
      might be improved with more comprehensive indicators of the health burden of high
      and low temperatures such as YLL. https://doi.org/10.1289/EHP1745.

PMID- 29342454
TI  - Sodium Trimetaphosphate as a Novel Strategy for Matrix Metalloproteinase
      Inhibition and Dentin Remineralization.
AB  - The effect of sodium trimetaphosphate (STMP) as an antiproteolytic and
      remineralizing agent on demineralized dentin was evaluated in vitro. The
      inhibitory potential of STMP at 0.5, 1.5, 3.5, and 5% against recombinant matrix
      metalloproteinases (MMPs) MMPs-2 and -9 was assessed by zymography. To
      investigate its remineralization potential, 40 bovine root specimens were
      obtained and subjected to a demineralization protocol to produce caries-like
      dentin lesions. After that, dentin surfaces were divided into 3 areas: (1)
      mineralized (no treatment); (2) demineralized; and (3) demineralized/treated with
      STMP and submitted to a pH-cycling associated or not with STMP (1.5, 3.5, or 5%
      STMP, 10 min of treatment). After that, superficial hardness (SH) and cross
      sectional hardness (CSH) were determined. Polarized light microscopy (PLM) was
      used to qualitatively evaluate mineralization within the caries-like lesions. The
      zymographic analysis showed that STMP solution is a potent inhibitor of the
      gelatinolytic activity of MMPs-2 and -9 depending on the dose, since the lowest
      concentration (0.5%) partially inhibited the enzyme activity, while the higher
      concentrations completely inhibited enzyme activity. Regarding remineralization
      effect, only 1.5% STMP solution enhanced both the SH and CSH. PLM showed that the
      area treated with 1.5% STMP presented similar birefringence as mineralized sound
      dentin. In conclusion, 1.5% STMP solution is effective as an antiproteolytic
      agent against MMPs and promotes dentin remineralization.

PMID- 29342453
TI  - Fine Particulate Air Pollution and the Expression of microRNAs and Circulating
      Cytokines Relevant to Inflammation, Coagulation, and Vasoconstriction.
AB  - BACKGROUND: MicroRNAs (miRNAs) are a key factor in epigenetic regulation of gene
      expression, but miRNA responses to fine particulate matter (PM2.5) air pollution
      and their potential contribution to cardiovascular effects of PM2.5 are unknown.
      OBJECTIVE: We explored the potential influence of PM2.5 on the expression of
      selected cytokines relevant to systemic inflammation, coagulation, and
      vasoconstriction, and on miRNAs that may regulate their expression. METHODS: We
      designed a double-blind, randomized crossover study in which true and sham air
      purifiers were used to expose 55 healthy young adult students in Shanghai, China,
      to reduced or ambient levels of indoor PM2.5 during two-week periods, and we
      measured the expression (mRNA and protein) of 10 serum cytokines, and miRNAs that
      target them, after each intervention period. We used linear mixed-effect models
      to estimate associations of the intervention, and time-weighted personal PM2.5
      exposures, with the cytokines, mRNA, and miRNAs; we also explored potential
      mediation by miRNAs. RESULTS: The findings were generally consistent for
      associations with the intervention and for associations with an interquartile
      range increase in time-weighted PM2.5. Specifically, higher PM2.5 exposure was
      positively associated with the expression (mRNA, protein, or both) of interleukin
      1 (encoded by IL1), IL6, tumor necrosis factor (encoded by TNF), toll-like
      receptor 2 (encoded by TLR2), coagulation factor 3 (encoded by F3), and
      endothelin 1 (encoded by EDN1), and was negatively associated with miRNAs (miR-21
      5p, miR-187-3p, miR-146a-5p, miR-1-3p, and miR-199a-5p) predicted to target mRNAs
      of IL1, TNF, TLR2, and EDN1. CONCLUSIONS: Our findings require confirmation but
      suggest that effects of PM2.5 on cardiovascular diseases may be related to acute
      effects on cytokine expression, which may be partly mediated through effects of
      PM2.5 on miRNAs that regulate cytokine expression.
      https://doi.org/10.1289/EHP1447.

PMID- 29342455
TI  - Endoscopic Full-Thickness Resection of a Colonic Lateral Spreading Tumor.
AB  - The Full-Thickness Resection Device (FTRD; Ovesco Endoscopy, Tubingen, Germany)
      combines endoscopic full-thickness resection (EFTR) of gastrointestinal lesions
      with closure and cutting of the tissue in one integrated procedure. It provides
      en-bloc resection with an integral wall specimen for histopathological
      evaluation. This resection technique is partially filling of the gaps between the
      current procedures of choice in endoscopy (endoscopic mucosal resection and
      endoscopic submucosal dissection) and surgery. We present the case of an EFTR
      procedure performed for a periappendicular lateral spreading tumor.

PMID- 29342456
TI  - Correlation between Resection Margin and Disease Recurrence with a Restricted
      Cubic Spline Model in Patients with Resected Hepatocellular Carcinoma.
AB  - BACKGROUND: The relationship between resection margin (RM) and recurrence of
      resected hepatocellular carcinoma (HCC) is unclear. METHODS: We reviewed clinical
      data for 419 patients with HCC. The oncologic outcomes were compared between 2
      groups of patients classified according to the inflexion point of the restricted
      cubic spline plot. RESULTS: The patients were divided according to an RM of <1 cm
      (n = 233; narrow RM group) or >=1 cm (n = 186; wide RM group). The 5-year
      recurrence-free survival (RFS) rate was lower (34.8 vs. 43.8%, p = 0.042) and
      recurrence near the resection site was more frequent (4.7 vs. 0%, p = 0.010) in
      the narrow RM group. Patients with multiple lesions, or prior transarterial
      chemoembolization (TACE) or radiofrequency ablation (RFA) were excluded from
      subgroup analyses. In patients with a 2-5 cm HCC, the 5-year RFS was greater in
      the wide RM group (54.4 vs. 32.5%, p = 0.036). Narrow RM (hazard ratio 1.750, 95%
      CI 1.029-2.976, p = 0.039) was independently associated with disease recurrence.
      CONCLUSION: In patients with a single 2-5 cm HCC without prior TACE/RFA, an RM of
      >=1 cm was associated with lower risk of recurrence after liver resection.

PMID- 29342457
TI  - The von Hippel-Lindau Gene Is Required to Maintain Renal Proximal Tubule and
      Glomerulus Integrity in Zebrafish Larvae.
AB  - BACKGROUND: von Hippel-Lindau (VHL) disease is characterized by the development
      of benign and malignant tumours in many organ systems, including renal cysts and
      clear cell renal cell carcinoma. It is not completely understood what underlies
      the development of renal pathology, and the use of murine Vhl models has been
      challenging due to limitations in disease conservation. We previously described a
      zebrafish model bearing inactivating mutations in the orthologue of the human VHL
      gene. METHODS: We used histopathological and functional assays to investigate the
      pronephric and glomerular developmental defects in vhl mutant zebrafish,
      supported by human cell culture assays. RESULTS: Here, we report that vhl is
      required to maintain pronephric tubule and glomerulus integrity in zebrafish
      embryos. vhl mutant glomeruli are enlarged, cxcr4a+ capillary loops are dilated
      and the Bowman space is widened. While we did not observe pronephric cysts, the
      cells of the proximal convoluted and anterior proximal straight tubule are
      enlarged, periodic acid schiff (PAS) and Oil Red O positive, and display a clear
      cytoplasm after hematoxylin and eosine staining. Ultrastructural analysis showed
      the vhl-/- tubule to accumulate large numbers of vesicles of variable size and
      electron density. Microinjection of the endocytic fluorescent marker AM1-43 in
      zebrafish embryos revealed an accumulation of endocytic vesicles in the vhl
      mutant pronephric tubule, which we can recapitulate in human cells lacking VHL.
      CONCLUSIONS: Our data indicates that vhl is required to maintain pronephric
      tubule and glomerulus integrity during zebrafish development, and suggests a role
      for VHL in endocytic vesicle trafficking.

PMID- 29342458
TI  - Glucocorticoids Modulate Th1 and Th2 Responses in Asthmatic Mouse Models by
      Inhibition of Notch1 Signaling.
AB  - BACKGROUND: Notch1 has been linked to the pathogenesis of asthma due to its
      contribution on Th1/Th2 imbalance. gamma-Secretase inhibitor (GSI) acts as an
      effective blocker of Notch1 signaling. Glucocorticoids (GCs) are the most
      effective anti-inflammatory drugs for asthma. The present study investigated the
      involvement of the Notch1 pathway in the anti-inflammatory effect of GCs and its
      association with Th1/Th2 balance. METHODS: The asthma model was established in
      BALB/c mice by sensitization with ovalbumin (OVA). Dexamethasone (DEX; 1 mg/kg)
      and/or GSI (0.03 mg/kg) was orally or intranasally administrated. RESULTS:
      Compared to the OVA-sensitized mice, the administration of DEX and/or GSI
      significantly ameliorated the airway inflammation infiltration, goblet cell
      metaplasia, and airway hyper-responsiveness. The expression of IL-4 and IL-13, as
      well as the ratios of eosinophils and lymphocytes, were significantly decreased,
      whereas IFN-gamma and IL-2 levels were significantly increased in bronchoalveolar
      lavage fluid after the administration of DEX and GSI. The expressions of the
      Notch1/NICD1 pathway were decreased after DEX and/or GSI administration in lung
      tissues, especially in CD4+ T cells. Also, a reduction of GATA3 and elevation of
      T-bet levels were correlated with the upregulation of Th1/Th2 ratios in lung
      tissues. CONCLUSIONS: Through the inhibition of Notch1 signaling, both GSI and
      GCs could regulate Th1/Th2 balance involved in allergic airway inflammation in
      OVA-induced asthma.

PMID- 29342459
TI  - Risk Factors and Clinical Features in Cashew Nut Oral Food Challenges.
AB  - BACKGROUND: Cashew nuts (CN) are capable of causing severe allergic reactions.
      However, little has been reported about the details of CN oral food challenges
      (OFC). METHODS: CN-specific IgE (sIgE) levels were measured for 1 year in 66
      patients who underwent an OFC with >3 g CN for diagnosis or confirmation of
      tolerance acquisition between June 2006 and August 2014. We retrospectively
      analyzed the OFC and patient background. RESULTS: The median (IQR) age of the 66
      patients (48 boys/men and 18 girls/women) was 7.0 years (5.7-8.8). Twelve
      patients (18.2%) had a positive OFC result; 6 of 8 (75%) patients with a history
      of an immediate reaction to CN failed the OFC. Anaphylaxis was experienced by 5
      of these 12 (42%) patients. A history of an immediate reaction to CN and the CN
      sIgE levels were significantly different for patients with a positive or negative
      OFC result (p < 0.01). Among patients without a previous immediate reaction to
      CN, the 95% positive predictive value (PPV) for the CN sIgE level for a positive
      OFC result was 66.1 kUA/L. CONCLUSIONS: A history of an immediate reaction to CN
      and high CN sIgE were risk factors for a positive OFC result. The number of
      positive OFC results was relatively low, but there was a high probability of
      anaphylaxis. We should consider the indication of OFC carefully for patients with
      a history of immediate reactions to CN and avoid OFC for patients without such a
      history whose CN sIgE values are >66.1 kUA/L (95% PPV).

PMID- 29342460
TI  - Role of the Frontal Sinus in Mediating Ocular Vestibular-Evoked Myogenic
      Potentials by Bone Vibration Stimuli Applied to the Forehead.
AB  - This study investigated ocular vestibular-evoked myogenic potential (oVEMP) tests
      via Fpz and Fz taps to assess the role of the frontal sinus in mediating oVEMP
      elicitation. Forty healthy subjects and 80 patients with Meniere disease (MD)
      underwent a series of oVEMP tests via a minishaker tapping at the Fpz and Fz
      sites in a randomized order. Response rates of oVEMP test via various tapping
      sites were compared. Dimensions of the frontal sinus were measured via CT scan. A
      significantly negative correlation between the age and height of the frontal
      sinus was noted, and the cutoff age for discriminating present and absent Fpz
      oVEMPs in MD patients was 52 years. Additionally, oVEMPs by Fpz tapping were more
      efficiently presented in males than females, likely because of the greater
      resonance by the larger height of the frontal sinus in males (3.88 +/- 0.68 cm)
      than females (3.42 +/- 0.67 cm). In conclusion, the height of the frontal sinus
      plays a role in mediating the elicitation of oVEMPs. The oVEMPs could be easily
      elicited by the first-order bone vibration (Fpz/Fz tapping) coupled with the
      second-order resonance effect (with a high extent of the frontal sinus). Thus,
      initial tapping at the Fpz site is suggested. If it fails, try the Fz site for
      screening the oVEMPs.

PMID- 29342461
TI  - Mechanism of Periostin Production in Human Bronchial Smooth Muscle Cells.
AB  - BACKGROUND: Asthma is a chronic airway inflammatory disease characterized by
      airway remodeling, in which the bronchial smooth muscle (BSM) cells play an
      important role. Periostin, a biomarker that reflects Th2-driven inflammatory
      diseases such as asthma, may play an important role in the asthmatic airway.
      Although periostin is mainly produced in airway epithelial cells and fibroblasts
      after interleukin (IL)-13 stimulation, whether BSM cells produce periostin
      remains unclear. Therefore, we investigated periostin production in BSM cells and
      the mechanisms involved. METHODS: Human BSM cells were cultured, and the effect
      of IL-13 stimulation on periostin production was evaluated using quantitative
      polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA). We
      evaluated the phosphorylation of signal transducer and activator of transcription
      factor 6 (STAT6), extracellular signal-regulated kinase (ERK)1/2, and Akt after
      IL-13 stimulation. Furthermore, using ELISA, we evaluated the influence of
      several phosphorylation inhibitors on periostin production. RESULTS: Periostin
      mRNA expression increased in a dose- and time-dependent manner after IL-13
      stimulation; periostin production was induced 24 and 48 h after stimulation. IL
      13 stimulation induced the phosphorylation of STAT6, ERK1/2, and Akt. IL-13
      induced periostin production was attenuated by inhibiting STAT6 phosphorylation
      and strongly suppressed by inhibiting mitogen-activated protein kinase kinase 1/2
      phosphorylation or phosphatidylinositol 3-kinase (PI3K) phosphorylation.
      CONCLUSIONS: BSM cells produced periostin after IL-13 stimulation, via the
      JAK/STAT6, ERK1/2, and PI3K/Akt pathways. Understanding the mechanism of
      periostin production in BSM cells may help to clarify asthma pathogenesis.

PMID- 29342462
TI  - Reference Values for Respiratory Muscle Strength in Children and Adolescents.
AB  - BACKGROUND: Measurement of respiratory muscle function is important in the
      diagnosis of respiratory muscle disease, respiratory failure, to assess the
      impact of chronic diseases, and/or to evaluate respiratory muscle function after
      treatment. OBJECTIVES: To establish reference values for maximal inspiratory and
      expiratory pressure, and the tension-time index at rest in healthy children and
      adolescents aged 8-19 years, as well as to present sex- and age-related reference
      centiles normalized for demographic and anthropometric determinants. METHODS: In
      this cross-sectional observational study, demographic, anthropometric, and
      spirometric data were assessed, as well as data on respiratory muscle strength
      (PImax and PEmax) and work of breathing at rest (TT0.1), in a total of 251
      children (117 boys and 134 girls; mean age 13.4 +/- 2.9 years). Reference values
      are presented as reference centiles developed by use of the lambda, mu, sigma
      method. RESULTS: Boys had significantly higher PImax and PEmax values. Next to
      sex and age, fat-free mass appeared to be an important predictor of respiratory
      muscle strength. Reference centiles demonstrated a slight, almost linear increase
      in PImax with age in boys, and a less steep increase with age in girls. TT0.1
      values did not differ between boys and girls and decreased linearly with age.
      CONCLUSION: This study provides reference values for respiratory muscle strength
      and work of breathing at rest. In addition to sex and age, fat-free mass was
      found to be an important predictor of respiratory muscle strength in boys and
      girls.

PMID- 29342463
TI  - Sensation of Cold during the Ice Water Test Corresponds to the Perception of Pain
      during Botulinum Toxin Bladder Wall Injections.
AB  - AIMS: To investigate the association of bladder cold sensation (BCS) during the
      ice water test (IWT) and pain perception when botulinum toxin injections (BTI)
      are administered into the bladder wall. MATERIAL AND METHODS: In 86 patients with
      idiopathic overactive bladder, the BCS during the IWT was investigated. Patients
      were divided into 2 groups: with and without BCS. During subsequent
      administration of BTI, the number of perceived and painful injections as well as
      the pain levels on a 0-100 pain scale were compared in both groups using Student
      t test. RESULTS: Thirty-five patients reported a BCS, while 51 did not. After 10
      BTI, the mean number of perceived injections was 7.9 in patients with and 2.4 in
      patients without BCS (p < 0.0001). The mean number of painful injections was 5.4
      in patients with BCS and 4.3 in patients without (p < 0.001). Mean levels on a 0
      100 pain scale were 33.7 in patients with and 17.8 in patients without cold
      sensation (p < 0.0001). CONCLUSION: The association of BCS during the IWT and
      pain to during BTI may implicate that the perceptions of cold and pain in the
      urinary bladder may use similar receptors and neuronal pathways.

PMID- 29342464
TI  - Risk Factors for Intraoperative Hypocapnia in Pediatric Neurosurgical Patients: A
      Retrospective Cohort Study.
AB  - BACKGROUND: Hypocapnia has been associated with an increased risk and adverse
      outcomes in the injured brain. This study aimed to identify risk factors of
      intraoperative hypocapnia in pediatric neurosurgical patients when tidal volumes
      and respiratory rates were determined based on their weight and age,
      respectively. METHODS: Electronic medical records of pediatric patients (<=18
      years) who underwent neurosurgery from December 2014 to January 2016 were
      retrospectively reviewed. Minute ventilation was fixed according to each
      patient's weight and age. Hypocapnia was defined as arterial partial pressure of
      carbon dioxide <35 mm Hg from intraoperative arterial blood gas analysis.
      Patients were divided into hypocapnia and nonhypocapnia groups. Risk factors for
      intraoperative hypocapnia were found using univariable and multivariable logistic
      regression analyses. RESULTS: Of the 333 pediatric patients analyzed, 101 (30%)
      and 232 (70%) were included in the hypocapnia and nonhypocapnia groups,
      respectively. There was no difference in the minute ventilation between the two
      groups. The hypocapnia group had more patients taking valproate (8.9 vs. 2.2%; p
      = 0.008; OR, 4.441; 95% CI, 1.449-13.61) and carbonic anhydrase inhibitors (7.9
      vs. 2.2%; p = 0.018; OR, 3.905; 95% CI, 1.245-12.25). An operation for
      hydrocephalus was more commonly performed in the hypocapnia group (26.7 vs.
      15.9%; p = 0.017; OR, 1.923; 95% CI, 1.094-3.379). In the multivariable
      regression analysis, valproate (OR, 3.939; 95% CI, 1.250-12.41; p = 0.019),
      carbonic anhydrase inhibitor (OR, 3.345; 95% CI, 1.029-10.88; p = 0.045), and
      operation for hydrocephalus (OR, 1.838; 95% CI, 1.032-3.272; p = 0.039) were
      independent risk factors for intraoperative hypocapnia. CONCLUSIONS: Pediatric
      patients taking valproate and carbonic anhydrase inhibitors and who were
      scheduled for surgery of hydrocephalus were at risk of developing intraoperative
      hypocapnia during neurosurgery, a finding warning the surgeon that a conventional
      ventilatory strategy would endanger these patients.

PMID- 29342466
TI  - Deep Vein Thrombosis: A Rare Cause of Acute Testicular Pain. Case Report:
      Literature Review.
AB  - INTRODUCTION: Thrombosis is defined as the formation of a clot in a blood vessel
      that obstructs the flow of blood to the peripheral tissues. The incidence of
      thromboembolic disease ranges from 0.7 to 1.2% within urology. CASE REPORT: A 40
      year-old warehouse worker male presented to the emergency department with
      worsening of a month's lasting scrotal pain. Physical examination showed the
      presence of an enlarged and painful left testicle with no other findings. Right
      testicle, penis and abdominal examination showed no abnormalities whatsoever.
      Bilateral varicocele with a partial thrombosis of the left one associated with
      left inguinal hernia was diagnosed by performing an urgent testicular ultrasound
      test. Conservative treatment was first given. However, since pain was not
      relieved, surgery was indicated with left varicocelectomy and a left inguinal
      hernia repair procedure leading to complete symptoms control and normal
      testicular flow in the control Doppler ultrasound study 2 months after the
      surgery. CONCLUSION: Spontaneous thrombosis of the pampiniform plexus is a rare
      entity where the management remains controversial. The clinical case we report
      here shows that surgery may be considered an effective option.

PMID- 29342465
TI  - De Novo Bladder Urothelial Neoplasm in Renal Transplant Recipients: A
      Retrospective, Multicentered Study.
AB  - BACKGROUND AND OBJECTIVES: Renal transplant recipients (RTRs) have a 2- to 7-fold
      risk of developing a neoplasm compared to general population. Bladder urothelial
      neoplasms in this cohort has an incidence of 0.4-2%. Many reports describe a more
      aggressive behavior. The objective of this study is to describe oncologic
      characteristics of bladder urothelial neoplasms in RTRs and to evaluate its
      recurrence, progression, and survival rates. METHODS: A retrospective
      multicentered study was performed evaluating all de novo bladder urothelial
      neoplasms cases in RTRs from 1988 to 2014. Descriptive statistical analysis and
      evaluation of recurrence, progression, and survival rates were performed.
      RESULTS: A total of 28 de novo bladder transitional cell carcinomas (TCCs) were
      identified (incidence rate 0.64%). Cancer-specific survival rates were 100, 75,
      and 70% after 1, 5, and 10 years, respectively. Age at diagnosis superior to 60
      years was found to be a statistically significant variable for recurrence risk.
      Progression rate was 14%. Presence of CIS was significantly associated with
      progression. All cancer-specific deaths were in the high-risk group and all were
      progressions from non-muscle invasive to muscle invasive bladder cancer.
      CONCLUSIONS: Bladder urothelial neoplasms following renal transplant is
      associated with a trend toward worst prognosis. Early aggressive treatments, such
      as early radical cystectomy, might be advisable to reduce cancer-specific deaths.

PMID- 29342467
TI  - Boiling and Pressure Cooking Impact on IgE Reactivity of Soybean Allergens.
AB  - BACKGROUND: Soybean is one of the 8 foods that causes the most significant rate
      of food allergies in the USA and Europe. Thermal processing may impact on the
      allergenic potential of certain foods. We aimed to investigate modifications of
      the IgE-binding properties of soybean proteins due to processing methods that
      have been previously found to impact on the allergenicity of legumes such as
      peanut. METHODS: Soybean seeds were subjected to different thermal processing
      treatments. To evaluate their impact on the IgE-binding capacity of soybean
      proteins, individual sera from 25 patients sensitized to soybean were used in in
      vitro immunoassays. Detection of specific soybean allergens in untreated and
      treated samples was carried out with specific monoclonal and polyclonal
      antibodies. In vivo studies of skin prick testing (SPT) were also performed.
      RESULTS: The IgE reactivity of soybean was resistant to boiling up to 30 min, and
      this treatment had a higher impact when applied for 60 min. Treatment that
      combined heat and pressure produced a fragmentation of proteins in both soluble
      and insoluble fractions that went along with a decreased capacity to bind IgE and
      reduced the SPT wheal size. However, allergens such as 7S globulins survived this
      treatment. CONCLUSIONS: Thermal-processing methods able to attenuate the capacity
      of soybean proteins to bind IgE may contribute to the improvement of food safety
      and could constitute a potential strategy for the induction of tolerance to
      soybean.

PMID- 29342468
TI  - The Role of History of Gastro-Duodenal Ulcer in Patients with Upper
      Gastrointestinal Bleeding.
AB  - BACKGROUND: Some scoring systems have been introduced to predict the need for
      performing urgent endoscopy in patients with upper gastrointestinal bleeding
      (UGIB). However, in an emergency situation, this intervention is insufficient and
      cannot easily provide the required treatment. AIM: To identify new risk factors
      that can predict the need for endoscopic intervention (EI) in UGIB patients.
      METHODS: This is a retrospective cross-sectional study. Patients with UGIB
      admitted from April 2011 to August 2014 were included. The proportion of cases
      requiring EI and clinical factors (age, gender, antiplatelet/anticoagulant
      therapy, history of gastro-duodenal ulcer (GDU), systolic blood pressure, heart
      rate, hemoglobin, mean corpuscular volume, blood urea nitrogen-creatinine ratio
      (BUN/Cr ratio), prothrombin time-international normalized ratio, and Glasgow
      Blatchford Score (GBS) were analyzed using logistic regression models. RESULT: Of
      378 patients who were included in this study, 180 were found to be with GDU. The
      proportion of cases requiring EI was significantly higher in those with GDU than
      in other causes except variceal bleeding (53.5 vs. 37.0%, p < 0.01). Multivariate
      analysis revealed that a history of GDU was an independent risk factor (OR 1.78,
      95% CI 1.06-3.00) in addition to BUN/Cr ratio (OR 1.02, 95% CI 1.00-1.03) and GBS
      (OR 1.19, 95% CI 1.08-1.33). CONCLUSION: A history of GDU was an independent risk
      factor for predicting the need for EI in UGIB in addition to BUN/Cr ratio and
      GBS.

PMID- 29342469
TI  - The 2017 Update of the German Clinical Guideline on Epidemiology, Diagnostics,
      Therapy, Prevention, and Management of Uncomplicated Urinary Tract Infections in
      Adult Patients: Part 1.
AB  - OBJECTIVES: We aimed to update the 2010 evidence- and consensus-based national
      clinical guideline on the diagnosis and management of uncomplicated urinary tract
      infections (UTIs) in adult patients. MATERIALS AND METHODS: An interdisciplinary
      group consisting of 17 representatives of 12 medical societies and a patient
      representative was formed. Systematic literature searches were conducted in
      MEDLINE, -EMBASE, and the Cochrane Library to identify literature published in
      2010-2015. RESULTS: We provide 75 recommendations and 68 statements in the
      updated evidence- and consensus-based national clinical guideline. The
      diagnostics part covers practical recommendations on cystitis and pyelonephritis
      for each defined patient group. Clinical examinations, as well as laboratory
      testing and microbiological pathogen assessment, are addressed. CONCLUSION: In
      accordance with the global antibiotic stewardship initiative and considering new
      insights in scientific research, we updated our German clinical UTI guideline to
      promote a responsible antibiotic use and to give clear hands-on recommendations
      for the diagnosis and management of UTIs in adults in Germany for healthcare
      providers and patients.

PMID- 29342470
TI  - "Nested Type" Bladder Cancer: Myth or Reality?

PMID- 29342471
TI  - Extra-articular manifestations and burden of disease in patients with
      radiographic and non-radiographic axial spondyloarthritis.
AB  - OBJECTIVE: Although the prevalence of peripheral and extra-articular disease in
      ankylosing spondylitis (AS) has been assessed in many studies, data on non
      radiographic axial spondyloarthritis (nr-axSpA) is scanty. The aim of this study
      was first, to compare radiographic-axSpA/AS (r-axSpA/AS) and nr-axSpA concerning
      peripheral arthritis and extra-articular manifestations (EAMs), and second, to
      assess potential differences between patient subgroups with or without EAMs
      regarding disease burden. METHODS: Data was extracted from our single center
      axSpA database. Patients having at least one of the EAMs (uveitis and/or
      inflammatory bowel disease (IBD) and/or psoriasis) were compared to those who did
      not have EAMs. Patients' clinical data including disease activity, functional and
      psychological status, physical limitations, quality of life (QoL) and magnetic
      resonance imaging of sacroiliac joints (SIJ MR) were evaluated. RESULTS: Patients
      with nr-axSpA (n=193) were younger, had female predominance, better functional
      and physical status, higher frequency of bone edema in SIJ MR and peripheral
      arthritis but similar QoL, prevalence of HLA B27 and EAMs compared to r-axSpA/AS
      (n=352). The prevalence of current or ever uveitis (14.5 vs 15.3%, p=0.791),
      psoriasis (6.2 vs 5.4%, p=0.689) or IBD (4.1 vs 3.4%, p=0.663) in nr-axSpA and r
      axSpA/AS were similar. In both subgroup of patients, EAMs positive and negative
      patients had similar functional status and QoL, as well as disease activity and
      laboratory parameters. CONCLUSION: Patients with nr-axSpA and r-axSpA/AS have
      similar prevalence of EAMs and clinical burden of disease. Having EAMs does not
      have a major influence on clinical parameters and patient reported outcome
      measures in nr-axSpA and r-axSpA/AS.

PMID- 29342472
TI  - Standard practice aiming clinical excellence in rheumatology.

PMID- 29342473
TI  - Effectiveness of early adalimumab therapy in psoriatic arthritis patients from
      Reuma.pt - EARLY PsA.
AB  - Objective To compare outcomes in psoriatic arthritis (PsA) patients initiating
      adalimumab (ADA), with short- and long-term disease duration and to evaluate the
      potential effect of concomitant conventional synthetic disease-modifying
      antirheumatic drugs (csDMARD) or glucocorticoids. Methods Analyses included adult
      PsA patients registered in the Rheumatic Diseases Portuguese Register (Reuma.pt)
      between June 2008-June 2016 who received ADA for >=3 months. Psoriatic Arthritis
      Response Criteria (PsARC) response, tender and swollen joint count, inflammatory
      parameters, patient (PtGA) and physician global assessment (PhGA), Disease
      Activity Score-28 joints (DAS28), and Health Assessment Questionnaire Disability
      Index (HAQ-DI) were compared between patients with <5 years of disease (early
      PsA) and those with >=5 years of disease duration (late PsA). Time to achieving
      PsARC response was estimated using the Kaplan-Meier method. Results Of 135 PsA
      patients treated with ADA, 126 had information on disease duration (earlyPsA,
      n=41). PsARC response was achieved by 72.9% of the patients (88.0% early PsA vs
      62.2% late PsA; P=0.022) after 3 months and by 85.4% after 24 months (100% early
      PsA vs 75.9% late PsA; P=0.044). Early PsA patients achieved significantly less
      painful joints (2.7 vs 6.7, p=0.006), lower mean C-reactive protein (0.5 mg/dL vs
      1.3 mg/dL; P=0.011), and PhGA (18.3 vs 28.1; P=0.020) at 3 months. In the long
      term, early PsA patients also had fewer swollen joints (0.3 vs 1.7; P=0.030) and
      lower PhGA (6.3 vs 21.9; P<0.001), C-reactive protein (0.4 mg/dL vs 1.0 mg/dL;
      P=0.026), and DAS28 (2.2 vs 3.2; P=0.030). HAQ-DI decreased in both groups
      reaching a mean value at 24 months of 0.4 and 0.8 (P=ns) in early and late PsA,
      respectively. Early PsA patients obtained PsARC response more rapidly than late
      PsA (3.8 and 7.4 months, respectively; P=0.008). Concomitant csDMARDs showed
      clinical benefit (2-year PsARC response, 88.3% vs 60.0%; P=0.044). Concomitant
      glucocorticoids had no effect on PsARC response over 2 years of follow-up.
      Persistence on ADA was similar in both groups. Conclusion Early PsA patients had
      a greater chance of improvement after ADA therapy and better functional outcome,
      and achieved PsARC response more rapidly than late PsA. In this cohort,
      comedication with csDMARDs was beneficial over 2 years.

PMID- 29342474
TI  - The importance of quality of life for work outcomes in patients with ankylosing
      spondylitis - a cross-sectional study.
AB  - AIMS: Work impairment is one of the most important exploration and one of the
      aims of rheumatologists. We aimed to determine the risk factors for employment
      state and predictive factors of work outcomes using multi-dimensional measures in
      patients with ankylosing spondylitis (AS) in this comprehensive study. METHODS:
      One hundred patients with AS (31 females and 69 males) were included into this
      study. Demographic properties, local factors, disease activity (BASDAI),
      functionality (BASFI), spinal mobility (BASMI), radiologic stage (BASRI), quality
      of life (AS-QoL), cardiopulmonary involvement, exercise stress test and work
      outcomes were investigated and compared in employed and un-employed patients. The
      work instability scale (AS-WIS) and work productivity activity impairment scale
      (WPAI:SpA) were selected as work outcomes. The predictive factors were analyzed
      using multiple stepwise linear regressions. MAJOR RESULTS: Thirty-two patients
      (mean age: 42,6+/-11.7) were unemployed and the risk factors for unemployment
      state were female sex, lower annual income level, and older age. Work disability
      was detected only in 5% of patients. Decreased chest mobility (beta: -0.398, p:
      <0.001), low annual income level (beta:-0.291, p:<0.001), higher co-morbidities
      (beta:0.237, p:0.004), poorer AS-QoL (beta:0.238, p:0,012) and poorer AS-WIS
      score (beta:0.289, p: 0,004) were the predictors of work impairment. The
      predictive factors for work instability were higher work impairment (beta:0.533,
      p<0.001) and poorer AS-QoL (beta: 0.426, p<0.001) scores. CONCLUSIONS: Employment
      state mainly depends on contextual factors including male sex, higher income, and
      younger age. Socioeconomic factors as well as clinical data such as QoL were
      predictive for work productivity. Poorer AS-QoL was also a predictive factor for
      work instability.We suggested effective interventions to improve clinical and
      economic status in patients with AS.

PMID- 29342475
TI  - Sexual dysfunction in systemic lupus erythematosus patients.

PMID- 29342476
TI  - [Determinants of the Distance-Related Choice of Physician Using the Example of
      Patients with Psoriasis and Chronic Wounds].
AB  - STUDY AIM: There is only little knowledge about the influence of individual and
      sociodemographic characteristics determining patients' choice of their
      physicians. Furthermore, the role of patients' mobility is not clear. The primary
      aim of this study was the analysis of patients' decision patterns when choosing a
      physician. Patients' mobility as well as sociodemographic aspects were included
      in the analysis. METHODS: A multicenter cross-sectional study was conducted. Data
      were assessed at office-based dermatologists and at the University Medical Center
      Hamburg-Eppendorf. Patients with psoriasis and chronic wounds were interviewed
      about their behaviour when choosing a physician. Data analysis was performed
      using descriptive and multivariate methods. RESULTS: Data on 309 patients (50.5%
      male, mean age 58.3 years) were analysed. 211 patients were recruited at the
      outpatient unit of the university clinic, 98 at office-based physicians. The
      decision to visit a physician is primarily influenced by the physicians'
      competence, his range of service and the physician-patient relationship. The
      perspective of a better therapy as well as worsening of quality of life are
      responsible for a higher motivation to travel a longer distance to the physician.
      CONCLUSION: The results show a complex behaviour pattern of patients when
      choosing a physician. The physician's competence and his range of services are
      crucial for the patients' decision. The results also show that patients are
      willing to travel longer distances than necessary.

PMID- 29342477
TI  - [New Challenges: Diagnosis of Brain Death in Newborn, Children and Adolescents].
AB  - BACKGROUND: According to the current update of the German guideline on brain
      death (BD), participation of paediatricians is now mandatory for the examination
      of BD in patients younger than 14 years. The present analysis focuses on the
      previous practice and highlights the challenges that arise from the current
      update. METHODS: Retrospective evaluation of the patient registry of the German
      organ procurement organisation (north-eastern bureau) between January, 2001 and
      December, 2010 with specified paediatric age groups according to the 4th update
      of the German guideline on BD from the 1st of July 2015. RESULTS: 133 patients (0
      17 years) received at least one BD examination. Secondary brain damage was most
      frequent within the first 6 months of life whereas traumatic and other causes of
      primary brain damage were predominantly observed thereafter. The number of
      patients who received BD examination by paediatricians or were treated on
      neonatal/paediatric intensive care units declined with increasing age. In more
      than two-third of all paediatric patients, no paediatrician was involved in BD
      diagnostics. DISCUSSION: After enforcement of the 4th update of the German
      guideline on BD, the participation of qualified paediatric physicians must be
      increased significantly compared to previous practice. Advancements in the
      specialist training of paediatric physicians, adjustments in patient-centered
      paediatric care and interdisciplinary diagnostic teams may be solutions to meet
      this demand.

PMID- 29342478
TI  - Design and Implementation of a Visual Analytics Electronic Antibiogram within an
      Electronic Health Record System at a Tertiary Pediatric Hospital.
AB  - BACKGROUND: Hospitals use antibiograms to guide optimal empiric antibiotic
      therapy, reduce inappropriate antibiotic usage, and identify areas requiring
      intervention by antimicrobial stewardship programs. Creating a hospital
      antibiogram is a time-consuming manual process that is typically performed
      annually. OBJECTIVE: We aimed to apply visual analytics software to electronic
      health record (EHR) data to build an automated, electronic antibiogram ("e
      antibiogram") that adheres to national guidelines and contains filters for
      patient characteristics, thereby providing access to detailed, clinically
      relevant, and up-to-date antibiotic susceptibility data. METHODS: We used visual
      analytics software to develop a secure, EHR-linked, condition- and patient
      specific e-antibiogram that supplies susceptibility maps for organisms and
      antibiotics in a comprehensive report that is updated on a monthly basis.
      Antimicrobial susceptibility data were grouped into nine clinical scenarios
      according to the specimen source, hospital unit, and infection type. We
      implemented the e-antibiogram within the EHR system at Children's Hospital of
      Philadelphia, a tertiary pediatric hospital and analyzed e-antibiogram access
      sessions from March 2016 to March 2017. RESULTS: The e-antibiogram was
      implemented in the EHR with over 6,000 inpatient, 4,500 outpatient, and 3,900
      emergency department isolates. The e-antibiogram provides access to rolling 12
      month pathogen and susceptibility data that is updated on a monthly basis. E
      antibiogram access sessions increased from an average of 261 sessions per month
      during the first 3 months of the study to 345 sessions per month during the final
      3 months. CONCLUSION: An e-antibiogram that was built and is updated using EHR
      data and adheres to national guidelines is a feasible replacement for an annual,
      static, manually compiled antibiogram. Future research will examine the impact of
      the e-antibiogram on antibiotic prescribing patterns.

PMID- 29342479
TI  - Time Spent on Dedicated Patient Care and Documentation Tasks Before and After the
      Introduction of a Structured and Standardized Electronic Health Record.
AB  - BACKGROUND: Physicians spend around 35% of their time documenting patient data.
      They are concerned that adopting a structured and standardized electronic health
      record (EHR) will lead to more time documenting and less time for patient care,
      especially during consultations. OBJECTIVE: This study measures the effect of the
      introduction of a structured and standardized EHR on documentation time and time
      for dedicated patient care during outpatient consultations. METHODS: We measured
      physicians' time spent on four task categories during outpatient consultations:
      documentation, patient care, peer communication, and other activities. Physicians
      covered various specialties from two university hospitals that jointly
      implemented a structured and standardized EHR. Preimplementation, one hospital
      used a legacy-EHR, and one primarily paper-based records. The same physicians
      were observed 2 to 6 months before and 6 to 8 months after implementation.We
      analyzed consultation duration, and percentage of time spent on each task
      category. Differences in time distribution before and after implementation were
      tested using multilevel linear regression. RESULTS: We observed 24 physicians
      (162 hours, 439 consultations). We found no significant difference in
      consultation duration or number of consultations per hour. In the legacy-EHR
      center, we found the implementation associated with a significant decrease in
      time spent on dedicated patient care (-8.5%). In contrast, in the previously
      paper-based center, we found a significant increase in dedicated time spent on
      documentation (8.3%) and decrease in time on combined patient care and
      documentation (-4.6%). The effect on dedicated documentation time significantly
      differed between centers. CONCLUSION: Implementation of a structured and
      standardized EHR was associated with 8.5% decrease in time for dedicated patient
      care during consultations in one center and 8.3% increase in dedicated
      documentation time in another center. These results are in line with physicians'
      concerns that the introduction of a structured and standardized EHR might lead to
      more documentation burden and less time for dedicated patient care.

PMID- 29342480
TI  - Phenolic Compounds as Arginase Inhibitors: New Insights Regarding Endothelial
      Dysfunction Treatment.
AB  - Endothelial dysfunction is characterised by the low bioavailability of nitric
      oxide with a relevant negative impact on the nitric oxide/cGMP pathway. The loss
      of nitric oxide/cGMP signaling may be caused by an increased arginase activity.
      Plant-derived substances, especially polyphenols, are compounds that have the
      potential to inhibit arginase activity and they may represent an attractive
      therapeutic option to combat clinical outcomes related to endothelial
      dysfunction. An extensive review was carried out using all available data
      published in English in the Pubmed database, and without restriction regarding
      the year of publication. Despite the increased number of new substances that have
      been tested as arginase inhibitors, it is rare to find a compound that satisfies
      all the toxicological criteria to be used in the development of a new drug. On
      the other hand, recent data have shown that substances from plants have great
      potential to be applied as arginase inhibitors, most of which are polyphenols. Of
      the relevant mechanisms in this process, the inhibition of arginase by natural
      products seems to act against endothelial dysfunction by reestablishing the
      vascular function and elevating nitric oxide levels (by increasing the amounts of
      substrate (L-arginine, and endothelial nitric oxide synthase activation and
      stabilisation) as well as decreasing the generation of reactive species (formed
      by uncoupledendothelial nitric oxide synthase). This review summarises several
      topics regarding arginase inhibition by natural substances as well as indicating
      this pathway as an emergent strategy to elevate nitric oxide levels in disorders
      involving endothelial dysfunction. In addition, some aspects regarding structural
      activity and future perspectives are discussed.

PMID- 29342481
TI  - [Pioneering research developments in psychiatry].

PMID- 29342482
TI  - [Driving ability with neurological diseases].

PMID- 29342483
TI  - [Fitness to drive after stroke].
AB  - In Germany, patient information and expert testimony on driving ability requires
      knowledge of the corresponding legislation and the Guideline for expertises on
      driver aptitude. The testimony should clearly identify handicaps with regard to
      driving, give estimates on the future risks of a sudden loss of control, and also
      consider personal attitudes such as inadequate behavior, lack of insight etc.
      Physical handicaps often can be compensated for by restrains or restrictions such
      as vehicle modifications, daylight driving only etc.Both, information and
      testimony must give estimates on the risks of a sudden loss of control while
      driving by stroke recurrence or epileptic seizures. In accordance with the Risk
      of-Harm-Formula of the Canadian Cardiovascular Society methods are being
      discussed, by which an estimate of harmful traffic accidents due to stroke
      recurrence can be calculated.

PMID- 29342484
TI  - [(Neuro-)ophthalmogical aspects of driving ability].
AB  - The requirements regarding visual functioning needed for driving ability are
      stipulated in Annex 6 of the German driving licence regulations: In case of a
      visual disorder an ophthalmological assessment is essential: It is of crucial
      importance for the examining ophthalmologist to exhaust all ocular-medical
      possibilities to enable the applicant to maintain or regain his driving
      permission. In the overwhelming majority of the cases this is eminently
      feasible.However, there is no way to attest driving ability in a patient
      suffering acute one-sided visual loss for a period of 3 months on the basis of
      legal recommendations. Concerning oculomotor disturbances, the expansion of the
      diplopic central visual field and the subjective restriction caused thereby are
      important: the central 20 degree area must be free of diplopia.According to the
      German driving license regulations, absolute homonymous visual field defects such
      as hemianopsia or quadrantic defects affecting the visual centre are incompatible
      with driving an automobile. Even training measures causing the patient to
      experience a sense of smooth orientation do nothing to mitigate this fact.Dealing
      with serious disturbances of visual function, as a matter of principle an
      ophthalmologist should provide an additional expertise before a positive decision
      on driving ability is made.

PMID- 29342485
TI  - [Driving ability in mild cognitive impairment and dementia].
AB  - Executive functions, visuo-spatial processing and control of behaviour are
      pertinent for safe driving. In patients with mild cognitive impairment and
      dementia, these abilities can be impaired, in addition to age-related
      impairments, and driving ability can be compromised at an early stage.
      Neurologists and psychiatrists play an important role in the examination,
      counseling and, if required, the issuing of a medical driving ban. Mistakes in
      this process may ensue forensic sequelae for the involved physicians. The present
      article presents the relevant conditions and associated cognitive impairments,
      and gives some recommendations on the neuropsychological workup and on the
      communication with patients and relatives concerning driving.

PMID- 29342486
TI  - ?

PMID- 29342487
TI  - [Application of Intrabronchial Valves in High Risk Patients with Bronchopleural
      Fistula: an Alternative Therapeutic Option].
AB  - OBJECTIVES: Persistent air leak or bronchopleural fistula (BPF) is a challenging
      and frequently observed problem after pulmonary resection and may lead to
      prolonged chest tube therapy. One efficient nonsurgical approach to manage such a
      fistula is the application of intrabronchial valves. This may support earlier
      chest tube removal and hospital discharge. METHODS: Between 04/2015 and 03/2017,
      n = 8 patients (n = 4 female) with severe pleural empyema and necrotising lung
      tissue defects developed prolonged air leak and persistent BPF after surgery.
      Radiological and bronchoscopical investigations revealed the presence of a BPF.
      For closure, intrabronchial valves were endoscopically inserted into the affected
      bronchi. In patients with repeat development of empyema, a chest wall window was
      required (n = 6 patients). RESULTS: The mean age was 61 years (45 - 85 years).
      After repeated surgical debridement, the space was sterile and the chest wall
      window was closed. After valve placement, air leaks were no longer detectable. In
      all patients, the procedures were well tolerated without any negative events.
      After successful valve placement, chest tubes could be removed in all n = 8
      patients within 7 days (3 - 15 days) and patients were discharged thereafter.
      CONCLUSIONS: Placement of intrabronchial valves presents an alternative option to
      conventional surgical and non-surgical methods for the treatment of postoperative
      persistent air leak or BPF. Particularly in high risk patients, this procedure is
      safe and effective.

PMID- 29342488
TI  - The Effects of Folate Supplementation on Diabetes Biomarkers Among Patients with
      Metabolic Diseases: A Systematic Review and Meta-Analysis of Randomized
      Controlled Trials.
AB  - Although several studies have evaluated the effect of folate supplementation on
      diabetes biomarkers among patients with metabolic diseases, findings are
      inconsistent. This review of randomized controlled trials (RCTs) was performed to
      summarize the evidence on the effects of folate supplementation on diabetes
      biomarkers among patients with metabolic diseases. Randomized-controlled trials
      (RCTs) published in PubMed, EMBASE, Web of Science and Cochrane Library databases
      up to 1 September 2017 were searched. Two review authors independently assessed
      study eligibility, extracted data, and evaluated risk of bias of included
      studies. Heterogeneity was measured with a Q-test and with I2 statistics. Data
      were pooled by using the fix or random-effect model based on the heterogeneity
      test results and expressed as standardized mean difference (SMD) with 95%
      confidence interval (CI). A total of sixteen randomized controlled trials
      involving 763 participants were included in the final analysis. The current meta
      analysis showed folate supplementation among patients with metabolic diseases
      significantly decreased insulin (SMD -1.28; 95% CI, -1.99, -0.56) and homeostasis
      model assessment of insulin resistance (HOMA-IR) (SMD -1.28; 95% CI, -1.99, 
      0.56). However, folate supplementation did not affect fasting plasma glucose
      (FPG) (SMD -0.30; 95% CI, -0.63, 0.02) and hemoglobin A1C (HbA1c) (SMD -0.29; 95%
      CI, -0.61, 0.03). The results of this meta-analysis study demonstrated that
      folate supplementation may result in significant decreases in insulin levels and
      HOMA-IR score, but does not affect FPG and HbA1c levels among patients with
      metabolic diseases.

PMID- 29342489
TI  - Correction: Artificial intelligence may help in predicting the need for
      additional surgery after endoscopic resection of T1 colorectal cancer.

PMID- 29342490
TI  - Detection of early neoplasia in Barrett's esophagus using lectin-based near
      infrared imaging: an ex vivo study on human tissue.
AB  - BACKGROUND AND STUDY AIMS:  Endoscopic surveillance for Barrett's esophagus (BE)
      is limited by long procedure times and sampling error. Near-infrared (NIR)
      fluorescence imaging minimizes tissue autofluorescence and optical scattering. We
      assessed the feasibility of a topically applied NIR dye-labeled lectin for the
      detection of early neoplasia in BE in an ex vivo setting. METHODS:  Consecutive
      patients undergoing endoscopic mucosal resection (EMR) for BE-related early
      neoplasia were recruited. Freshly collected EMR specimens were sprayed at the
      bedside with fluorescent lectin and then imaged. Punch biopsies were collected
      from each EMR under NIR light guidance. We compared the fluorescence intensity
      from dysplastic and nondysplastic areas within EMRs and from punch biopsies with
      different histological grades. RESULTS:  29 EMR specimens were included from 17
      patients. A significantly lower fluorescence was found for dysplastic regions
      across whole EMR specimens (P < 0.001). We found a 41 % reduction in the
      fluorescence of dysplastic compared to nondysplastic punch biopsies (P < 0.001),
      with a sensitivity and specificity for dysplasia detection of 80 % and 82.9 %,
      respectively. CONCLUSION:  Lectin-based NIR imaging can differentiate dysplastic
      from nondysplastic Barrett's mucosa ex vivo.

PMID- 29342491
TI  - Covered vs. uncovered self-expandable metal stents for malignant distal biliary
      strictures: a systematic review and meta-analysis.
AB  - BACKGROUND: Self-expandable metal stents (SEMS) are used for palliation of distal
      malignant biliary strictures, but the role of covered SEMS is less clear. We
      performed an up-to-date meta-analysis to compare the performance of covered and
      uncovered SEMS in patients with unresectable distal malignant biliary strictures.
      METHODS: A computerized medical search was performed using MEDLINE, EMBASE, and
      the Cochrane Library between 2000 and December 2016 to identify all randomized
      trials that compared covered with uncovered SEMS in patients with distal
      malignant biliary strictures. Primary outcomes were stent failure and patient
      mortality; secondary outcomes were stent dysfunction and adverse events. Pooled
      estimates were computed using the random effects model. RESULTS: Overall, 11 RCTs
      involving 1272 patients were included. The primary outcomes of stent failure and
      patient mortality did not differ significantly between covered and uncovered SEMS
      (hazard ratio [HR] 0.68, 95 % confidence interval [CI] 0.40 - 1.17; HR 0.89, 95
      %CI 0.76 - 1.05, respectively). However, stent migration and sludge formation
      were much more common with covered SEMS (odds ratio [OR] 5.11, 95 %CI 1.84 -
      14.17; OR 2.46, 95 %CI 1.37 - 4.43). The use of covered SEMS was associated with
      a lower rate of tumor ingrowth (OR 0.21, 95 %CI 0.09 - 0.50) but a higher rate of
      tumor overgrowth (OR 2.00, 95 %CI 1.15 - 3.48) compared with uncovered stents.
      The rates of procedure-related adverse events were similar in both groups.
      CONCLUSION: There was a risk reduction of about 32 % for both stent failure and
      patient mortality with covered SEMS but this difference was not significant.
      Migration and sludge rates were higher with covered SEMS, whereas tumor ingrowth
      was more likely with uncovered SEMS. The data show no added benefit of covered
      SEMS; further stent evolution is desirable.

PMID- 29342492
TI  - Efficacy and safety of endoscopic radiofrequency ablation for unresectable
      extrahepatic cholangiocarcinoma: a randomized trial.
AB  - BACKGROUND:  Endoscopic placement of biliary stents to relieve jaundice is the
      main palliative treatment for unresectable extrahepatic cholangiocarcinoma.
      Endoscopic biliary radiofrequency ablation (RFA) has been reported to prolong
      stent patency, which may be beneficial in improving patient survival. However,
      available evidence is still insufficient, as most reported studies are
      retrospective case series. The aim of this study was to explore the clinical
      effect and safety of RFA in patients with unresectable extrahepatic
      cholangiocarcinoma. METHODS:  65 patients with unresectable extrahepatic
      cholangiocarcinoma, except Bismuth type III and IV hilar cholangiocarcinoma, were
      enrolled and randomly underwent either RFA combined with biliary stenting (RFA +
      stent group; n = 32) or biliary stent only (stent-only group; n = 33). Overall
      survival time, stent patency period, and postoperative adverse events were
      recorded. RESULTS:  In the 21-month follow-up period, the overall mean survival
      time was significantly longer in the RFA + stent group than in the stent-only
      group (13.2 +/- 0.6 vs. 8.3 +/- 0.5 months; P < 0.001). The mean stent patency
      period of the RFA + stent group was also significantly longer than that of the
      stent-only group (6.8 vs. 3.4 months; P = 0.02). There was no significant
      difference in the incidence of postoperative adverse events between the two
      groups (6.3 % [2/32] vs. 9.1 % [3/33]; P = 0.67). CONCLUSION:  Endoscopic RFA
      combined with stenting can significantly prolong survival and the stent patency
      period without increasing the incidence of adverse events in patients with
      extrahepatic cholangiocarcinoma patient, except Bismuth type III and IV hilar
      cholangiocarcinoma. This approach can be considered as a safe and effective
      palliative treatment for these patients.

PMID- 29342493
TI  - Molecular Docking Studies on Isocytosine Analogues as Xanthine Oxidase
      Inhibitors.
AB  - Flexible docking simulations were carried out on a series of isocytosine analogs
      as xanthine oxidase (XO) inhibitors. This was done by analysing the interaction
      of these compounds at the active site of XO. The binding free energies of the
      analogs were calculated using GoldScore. The binding modes of the best-fit
      conformation were studied, providing some handy important interactions. The
      results obtained henceforth provided an insight into the pharmacophoric
      structural requirements for XO inhibition for this class of molecules.

PMID- 29342494
TI  - How Does the Patient React After Reading the Informed Consent Form of a
      Gynecological Surgery? A Qualitative Study.
AB  - OBJECTIVE:  To analyze the reaction of women after reading the Informed Consent
      Form (ICF) before undergoing elective gynecological/urogynecological surgeries.
      METHODS:  A qualitative study with 53 women was conducted between September 2014
      and May 2015. The analysis of the content was conducted after a scripted
      interview was made in a reserved room and transcribed verbatim. We read the ICF
      once more in front of the patient, and then she was interviewed according to a
      script of questions about emotions and reactions that occurred about the
      procedure and her expectations about the intra- and postoperative period.
      RESULTS:  The women had a mean age of 52 years, they were multiparous, and most
      had only a few years of schooling (54.7%). The majority (60.4%) of them had
      undergone urogynecological surgeries. Hysterectomy and colpoperineoplasty were
      the most frequent procedures. Ten women had not undergone any previous abdominal
      surgery. Fear (34.6%) was the feeling that emerged most frequently from the
      interviews after reading the ICF, followed by indifference (30.8%) and
      resignation (13.5%). Nine women considered their reaction unexpected after
      reading the ICF. Three patients did not consider the information contained in the
      ICF to be sufficient, and 3 had questions about the surgery after reading the
      document. CONCLUSION:  Reading the ICF generates fear in most women; however,
      they believe this feeling did not interfere in their decision-making process.

PMID- 29342495
TI  - Improving Perinatology Residents' Skills in Breaking Bad News: A Randomized
      Intervention Study.
AB  - OBJECTIVE:  Breaking bad news (BBN) is particularly difficult in perinatology.
      Previous research has shown that BBN skills can be learned and improved when
      taught and practiced. This project evaluated whether a structured training
      session would enhance perinatology residents' skills in BBN. METHODS:  This was a
      randomized controlled intervention study with year 1 to 4 Perinatology residents
      from a medical school in Brazil, during the 2014/15 school year. A total of 61
      out of 100 (61%) eligible residents volunteered to a structured training program
      involving communicating a perinatal loss to a simulated patient (SP) portraying
      the mother followed by the SP's immediate feedback, both video recorded. Later,
      residents were randomly assigned to BBN training based on a setting, perception,
      invitation, knowledge, emotion and summary (SPIKES) strategy with video reviews
      (intervention) or no training (control group). All residents returned for a
      second simulation with the same SP blinded to the intervention and portraying a
      similar case. Residents' performances were then evaluated by the SP with a
      checklist. The statistical analysis included a repeated measures analysis of
      covariance (RM-ANCOVA). Complementarily, the residents provided their perceptions
      about the simulation with feedback activities. RESULTS:  Fifty-eight residents
      completed the program. The simulations lasted on average 12 minutes, feedback 5
      minutes and SPIKES training between 1h and 2h30m. There was no significant
      difference in the residents' performances according to the SPs' evaluations (p =
      0.55). The participants rated the simulation with feedback exercises highly.
      These educational activities might have offset SPIKES training impact.
      CONCLUSION:  The SPIKES training did not significantly impact the residents'
      performance. The residents endorsed the simulation with feedback as a useful
      training modality. Further research is needed to determine which modality is more
      effective.

PMID- 29342496
TI  - Adverse Events in the Treatment of Periprosthetic Fractures Around the Knee - a
      Clinical and Radiological Outcome Analysis.
AB  - BACKGROUND: The incidence of periprosthetic fractures associated with total knee
      arthroplasty (PpFxK) has been reported to be 0.3 - 5.5%. 40% of all cases are
      related to revision TKA. The most common localisation is the distal femur.
      Classification is performed according to Rorabeck (RB). RB I - II fractures are
      usually treated with locked plating and retrograde intramedullary nailing,
      whereas RB III fractures are an indication for revision arthroplasty using a
      hinged endoprosthesis. PpFxK of the patella can be classified according to
      Goldberg and PpFxK of the proximal tibia can be grouped as in Felix.
      Interprosthetic fractures can be regarded as a special type of PpFx. Due to the
      increasing numbers of TKA being performed, increasing numbers of adverse events
      in arthroplasty can be expected. Adverse events in the treatment of PpFxK occur
      in up to 41% of patients according to the literature and revision is needed in
      approximately 29% of all cases. Risk factors are age, osteoporosis, infection,
      malalignment, osteolysis/loosening of the implant and status post revision.
      PATIENTS: A clinical and radiographic follow-up was performed with 50 patients
      (14 men, 36 women) treated for PpFxK of the femur, tibia and patella between 2011
      and 2015 at the department of arthroplasty at a level 1 trauma center in Europe.
      RESULTS: The follow-up of all patients was 68%, with an average of 19.1 +/- 14.6
      (1 - 49) months between PpFxK and clinical follow-up. 16% of the patients were
      allocated for further treatment or revision surgery from other hospitals. The
      patients' median age was 78.0 +/- 8.8 (55 - 94) years. Most patients were
      affected by several orthopaedic and internal medical comorbidities. PpFxK
      classified as RB II were the most common fractures (60%, n = 30). PpFxK usually
      occurred 5.0 +/- 4.8 (0 - 20) years after index TKA (primary or revision TKA),
      mostly in patients with CR-retaining endoprosthesis, whereas PpFxK according to
      Felix occurred significantly earlier and mostly in hinged TKAs. Patients achieved
      on average a mean Oxford Knee Score of 31.1 +/- 9.9 (14 - 46) points. The
      functional Knee Society Score (KSS) was 52.6 +/- 24.4 (20 - 100) and the mean KSS
      was 58.7 +/- 26.8 (0 - 99) points (n = 25). Radiographic evaluation of the RB I -
      II patients showed frontal and sagittal malalignment in 20.6% of all cases after
      reduction and plate fixation. The overall rate of surgical adverse events was
      50%; 44% of all RB patients needed revision surgery. Adverse events comprised non
      union, failure of osteosynthesis, infection, wound healing disorders and re
      fractures in the RB II and the Felix subgroup. CONCLUSION: PpFxK are severe
      injuries and are associated with a high rate of adverse events related to
      treatment. Patients often have a complex background and a history of revision
      surgery or periprosthetic joint infection. The treatment of PpFxK should
      therefore take place at a centre with expertise in traumatology as well as in
      revision arthroplasty. Preoperative infection diagnostic testing as well as
      adequate imaging (X-rays and CT) are essential. We furthermore advise early
      evaluation of revision arthroplasty, especially in elderly patients suffering
      from PpFxK with insufficient bone quality around the TKA and closeness between
      fracture and TKA. In the case of plate fixation, it is important to give
      attention to correct reduction - to prevent non-union, loosening of the implant
      and failure of the osteosynthesis - as well as to consider double plating.

PMID- 29342497
TI  - Non-antipsychotic catecholaminergic drugs for antipsychotic-induced tardive
      dyskinesia.
AB  - BACKGROUND: Tardive dyskinesia (TD) is a disabling movement disorder associated
      with the prolonged use of antipsychotic medication. Several strategies have been
      examined in the treatment of TD. Currently, however, there is no clear evidence
      of the effectiveness of these drugs in TD and they have been associated with many
      side effects. One particular strategy would be to use pharmaceutical agents which
      are known to influence the catecholaminergic system at various junctures.
      OBJECTIVES: 1. To determine the effects of any of the following drugs for
      antipsychotic-induced TD in people with schizophrenia or other chronic mental
      illnesses.i. Drugs which influence the noradrenergic system.ii. Dopamine receptor
      agonists.iii. Dopamine receptor antagonists.iv. Dopamine-depletor drugs.v. Drugs
      that increase the production or release of dopamine.2. To examine whether any
      improvement occurred with short periods of intervention (less than 6 weeks) and,
      if this did occur, whether this effect was maintained at longer periods of follow
      up.3. To examine if there was a differential effect for the various compounds.4.
      To examine whether the use of non-antipsychotic catecholaminergic drugs are most
      effective in those with more recent onset TD (less than five years). SEARCH
      METHODS: We retrieved 712 references from searching the Cochrane Schizophrenia
      Group Trials Register (July 2015 and April 2017). We also inspected references of
      all identified studies for further trials and contacted authors of trials for
      additional information. SELECTION CRITERIA: We selected studies if they were
      randomised controlled trials focusing on people with schizophrenia or other
      chronic mental illnesses and antipsychotic-induced tardive dyskinesia. We
      compared the use of catecholaminergic interventions versus placebo, no
      intervention, or any other intervention for the treatment of antipsychotic
      induced tardive dyskinesia. DATA COLLECTION AND ANALYSIS: We independently
      extracted data from these trials and we estimated risk ratios (RRs) with 95%
      confidence intervals (CIs). We assumed that people who left the studies early had
      no improvement. MAIN RESULTS: There are 10 included trials (N = 261) published
      between 1973 and 2010; eight are new from the 2015 and 2017 update searches.
      Forty-eight studies are excluded. Participants were mostly chronically mentally
      ill inpatients in their 50s, and studies were primarily of short (2 to 6 weeks)
      duration. The overall risk of bias in these studies was unclear, mainly due to
      poor reporting of allocation concealment and generation of the sequence. Studies
      were also not clearly blinded and we are unsure if data are incomplete or
      selectively reported, or if other biases were operating.One small, three-arm
      trial found that both alpha-methyldopa (N = 20; RR 0.33, 95% CI 0.14 to 0.80; low
      quality evidence) and reserpine (N = 20; RR 0.52 95% CI 0.29 to 0.96; low-quality
      evidence) may lead to a clinically important improvement in tardive dyskinesia
      symptoms compared with placebo after 2 weeks' treatment, but found no evidence of
      a difference between alpha-methyldopa and reserpine (N = 20; RR 0.60, 95% CI 0.19
      to 1.86; very low quality evidence). Another small trial compared tetrabenazine
      and haloperidol after 18 weeks' treatment and found no evidence of a difference
      on clinically important improvement in tardive dyskinesia symptoms (N = 13; RR
      0.93, 95% CI 0.45 to 1.95; very low quality evidence). No study reported on
      adverse events.For remaining outcomes there was no evidence of a difference
      between any of the interventions: alpha-methyldopa versus placebo for
      deterioration of tardive dyskinesia symptoms (1 RCT; N = 20; RR 0.33, 95% CI 0.02
      to 7.32; very low quality evidence), celiprolol versus placebo for leaving the
      study early (1 RCT; N = 35; RR 5.28, 95% CI 0.27 to 102.58; very low quality
      evidence) and quality of life (1 RCT; N = 35; RR 0.87, 95% CI 0.68 to 1.12; very
      low quality evidence), alpha-methyldopa versus reserpine for deterioration of
      tardive dyskinesia symptoms (1 RCT; N = 20; not estimable, no reported events;
      very low quality evidence), reserpine or carbidopa/levodopa versus placebo for
      deterioration of tardive dyskinesia symptoms (2 RCTs; N = 37; RR 1.18, 95% CI
      0.35 to 3.99; very low quality evidence), oxypertine versus placebo for
      deterioration of mental state (1 RCT; N = 42; RR 2.20, 95% CI 0.22 to 22.45; very
      low quality evidence), dopaminergic drugs (amantadine, bromocriptine, tiapride,
      oxypertine, carbidopa/levodopa) versus placebo for leaving the study early (6
      RCTs; N = 163; RR 1.29, 95% CI 0.65 to 2.54; very low quality evidence), and
      tetrabenazine versus haloperidol for deterioration of tardive dyskinesia symptoms
      (1 RCT; N = 13; RR 1.17, 95% CI 0.09 to 14.92) and leaving the study early (1
      RCT; N = 13; RR 0.23, 95% CI 0.01 to 4.00). AUTHORS' CONCLUSIONS: Although there
      has been a large amount of research in this area, many studies were excluded due
      to inherent problems in the nature of their cross-over designs. Usually data are
      not reported before the cross-over and the nature of TD and its likely response
      to treatments make it imprudent to use this data. The review provides little
      usable information for service users or providers and more well-designed and well
      reported studies are indicated.

PMID- 29342498
TI  - Patient reminder and recall interventions to improve immunization rates.
AB  - BACKGROUND: Immunization rates for children and adults are rising, but coverage
      levels have not reached optimal goals. As a result, vaccine-preventable diseases
      still occur. In an era of increasing complexity of immunization schedules, rising
      expectations about the performance of primary care, and large demands on primary
      care providers, it is important to understand and promote interventions that work
      in primary care settings to increase immunization coverage. One common theme
      across immunization programs in many nations involves the challenge of
      implementing a population-based approach and identifying all eligible recipients,
      for example the children who should receive the measles vaccine. However, this
      issue is gradually being addressed through the availability of immunization
      registries and electronic health records. A second common theme is identifying
      the best strategies to promote high vaccination rates. Three types of strategies
      have been studied: (1) patient-oriented interventions, such as patient reminder
      or recall, (2) provider interventions, and (3) system interventions, such as
      school laws. One of the most prominent intervention strategies, and perhaps best
      studied, involves patient reminder or recall systems. This is an update of a
      previously published review. OBJECTIVES: To evaluate and compare the
      effectiveness of various types of patient reminder and recall interventions to
      improve receipt of immunizations. SEARCH METHODS: We searched CENTRAL, MEDLINE,
      Embase and CINAHL to January 2017. We also searched grey literature and trial
      registers to January 2017. SELECTION CRITERIA: We included randomized trials,
      controlled before and after studies, and interrupted time series evaluating
      immunization-focused patient reminder or recall interventions in children,
      adolescents, and adults who receive immunizations in any setting. We included no
      intervention control groups, standard practice activities that did not include
      immunization patient reminder or recall, media-based activities aimed at
      promoting immunizations, or simple practice-based awareness campaigns. We
      included receipt of any immunizations as eligible outcome measures, excluding
      special travel immunizations. We excluded patients who were hospitalized for the
      duration of the study period. DATA COLLECTION AND ANALYSIS: We used the standard
      methodological procedures expected by Cochrane and the Cochrane Effective
      Practice and Organisation of Care (EPOC) Group. We present results for individual
      studies as relative rates using risk ratios, and risk differences for randomized
      trials, and as absolute changes in percentage points for controlled before-after
      studies. We present pooled results for randomized trials using the random-effects
      model. MAIN RESULTS: The 75 included studies involved child, adolescent, and
      adult participants in outpatient, community-based, primary care, and other
      settings in 10 countries.Patient reminder or recall interventions, including
      telephone and autodialer calls, letters, postcards, text messages, combination of
      mail or telephone, or a combination of patient reminder or recall with outreach,
      probably improve the proportion of participants who receive immunization (risk
      ratio (RR) of 1.28, 95% confidence interval (CI) 1.23 to 1.35; risk difference of
      8%) based on moderate certainty evidence from 55 studies with 138,625
      participants.Three types of single-method reminders improve receipt of
      immunizations based on high certainty evidence: the use of postcards (RR 1.18,
      95% CI 1.08 to 1.30; eight studies; 27,734 participants), text messages (RR 1.29,
      95% CI 1.15 to 1.44; six studies; 7772 participants), and autodialer (RR 1.17,
      95% CI 1.03 to 1.32; five studies; 11,947 participants). Two types of single
      method reminders probably improve receipt of immunizations based on moderate
      certainty evidence: the use of telephone calls (RR 1.75, 95% CI 1.20 to 2.54;
      seven studies; 9120 participants) and letters to patients (RR 1.29, 95% CI 1.21
      to 1.38; 27 studies; 81,100 participants).Based on high certainty evidence,
      reminders improve receipt of immunizations for childhood (RR 1.22, 95% CI 1.15 to
      1.29; risk difference of 8%; 23 studies; 31,099 participants) and adolescent
      vaccinations (RR 1.29, 95% CI 1.17 to 1.42; risk difference of 7%; 10 studies;
      30,868 participants). Reminders probably improve receipt of vaccinations for
      childhood influenza (RR 1.51, 95% CI 1.14 to 1.99; risk difference of 22%; five
      studies; 9265 participants) and adult influenza (RR 1.29, 95% CI 1.17 to 1.43;
      risk difference of 9%; 15 studies; 59,328 participants) based on moderate
      certainty evidence. They may improve receipt of vaccinations for adult
      pneumococcus, tetanus, hepatitis B, and other non-influenza vaccinations based on
      low certainty evidence although the confidence interval includes no effect of
      these interventions (RR 2.08, 95% CI 0.91 to 4.78; four studies; 8065
      participants). AUTHORS' CONCLUSIONS: Patient reminder and recall systems, in
      primary care settings, are likely to be effective at improving the proportion of
      the target population who receive immunizations.

PMID- 29342500
TI  - Does Rheumatoid Arthritis Cause an Obesity Paradox? Comment on the Article by
      Sparks et al.

PMID- 29342501
TI  - Selective Activation of Tumor Necrosis Factor Receptor II Induces
      Antiinflammatory Responses and Alleviates Experimental Arthritis.
AB  - OBJECTIVE: Treg cells modulate immune responses and can suppress the development
      of autoimmune diseases. Tumor necrosis factor receptor II (TNFRII) has been
      recognized as a key receptor on these cells that facilitates expansion and
      stabilization of CD4+ Treg cells. The purpose of the present study was to
      investigate the therapeutic activity of a novel TNFRII agonist in experimental
      arthritis as well as the role of different Treg cell subsets. METHODS: A novel
      mouse TNFRII-selective fusion protein (EHD2-sc-mTNFR2 ) was generated by genetic
      engineering. Mouse T cells were incubated together with interleukin-2 and/or EHD2
      sc-mTNFR2 , and the effects on Treg cells were analyzed by flow cytometry. Mice
      with collagen-induced arthritis (CIA) were treated with EHD2-sc-mTNFR2 or saline,
      and the therapeutic effects were monitored and characterized. RESULTS: Selective
      activation of TNFRII was found to expand both CD4+ and CD8+ Treg cells. Moreover,
      TNFRII activation elevated the number of CD4+CD25+ and CD8+CD25+ Treg cells and
      increased the number of FoxP3-expressing cells in CD8+, but not CD4+, Treg cells,
      indicating different mechanisms of TNFRII-induced expansion of diverse T cell
      subsets with suppressive activity. In the CIA model, we demonstrated that
      administration of the TNFRII agonist EHD2-sc-mTNFR2 led to the expansion of both
      CD4+ and CD8+ Treg cells in vivo and induced antiinflammatory responses that
      alleviated arthritis. CONCLUSION: Our findings support the use of TNFRII
      selective therapeutics as an effective approach to the treatment of arthritic
      disease and possibly other inflammatory and autoimmune diseases.

PMID- 29342499
TI  - Efficacy and Safety of Cyclophosphamide Treatment in Severe Juvenile
      Dermatomyositis Shown by Marginal Structural Modeling.
AB  - OBJECTIVE: In patients with severe or refractory juvenile dermatomyositis (DM),
      second-line treatments may be required. Cyclophosphamide (CYC) is used to treat
      some connective tissue diseases, but evidence of its efficacy in juvenile DM is
      limited. This study was undertaken to describe clinical improvement in juvenile
      DM patients treated with CYC and model the efficacy of CYC treatment compared to
      no CYC treatment. METHODS: Clinical data on skin, global, and muscle disease for
      patients recruited to the Juvenile DM Cohort and Biomarker Study were analyzed.
      Clinical improvement following CYC treatment was described using unadjusted
      analysis. Marginal structural models (MSMs) were used to model treatment efficacy
      and adjust for confounding by indication. RESULTS: Compared to the start of CYC
      treatment, there were reductions at 6, 12, and 24 months in skin disease (P = 1.3
      * 10-10 ), global disease (P = 2.4 * 10-8 ), and muscle disease (P = 8.0 * 10-10
      ) for 56 patients treated with CYC in unadjusted analysis. Limited evidence
      suggested a reduction in glucocorticoid dose (P = 0.047) in patients treated with
      CYC. MSM analysis showed reduced global disease and skin disease in patients who
      started an ~6-month course of CYC treatment >12 months ago compared to patients
      never or not yet treated with CYC. In the treated patients, the modified skin
      Disease Activity Score for juvenile DM was 1.19 units lower (P = 0.0085) and the
      physician's global assessment was 0.66 units lower (P = 0.027). Minor adverse
      events were reported in 3 patients within 1 year of stopping CYC. CONCLUSION: Our
      findings indicate that CYC is efficacious with no short-term side effects.
      Improvements in skin, global, and muscle disease were observed. Further studies
      are required to evaluate longer-term side effects.

PMID- 29342502
TI  - Antiphospholipid Antibodies Inhibit Trophoblast Toll-Like Receptor and
      Inflammasome Negative Regulators.
AB  - OBJECTIVE: Women with antiphospholipid antibodies (aPL) are at risk for pregnancy
      complications associated with poor placentation and placental inflammation.
      Although these antibodies are heterogeneous, some anti-beta2 -glycoprotein I
      (anti-beta2 GPI) antibodies can activate Toll-like receptor 4 (TLR-4) and NLRP3
      in human first-trimester trophoblasts. The objective of this study was to
      determine the role of negative regulators of TLR and inflammasome function in aPL
      induced trophoblast inflammation. METHODS: Human trophoblasts were not treated or
      were treated with anti-beta2 GPI aPL or control IgG in the presence or absence of
      the common TAM (TYRO3, AXL, and Mer tyrosine kinase [MERTK]) receptor ligand
      growth arrest-specific protein 6 (GAS6) or the autophagy-inducer rapamycin. The
      expression and function of the TAM receptor pathway and autophagy were measured
      by quantitative reverse transcription-polymerase chain reaction (qRT-PCR),
      Western blotting, and enzyme-linked immunosorbent assay (ELISA). Antiphospholipid
      antibody-induced trophoblast inflammation was measured by qRT-PCR, activity
      assays, and ELISA. RESULTS: Anti-beta2 GPI aPL inhibited trophoblast TAM receptor
      function by reducing cellular expression of the receptor tyrosine kinases AXL and
      MERTK and the ligand GAS6. The addition of GAS6 blocked the effects of aPL on the
      TLR-4-mediated interleukin-8 (IL-8) response. However, the NLRP3 inflammasome
      mediated IL-1beta response was not affected by GAS6, suggesting that another
      regulatory pathway was involved. Indeed, anti-beta2 GPI aPL inhibited basal
      trophoblast autophagy, and reversing this with rapamycin inhibited aPL-induced
      inflammasome function and IL-1beta secretion. CONCLUSION: Basal TAM receptor
      function and autophagy may serve to inhibit trophoblast TLR and inflammasome
      function, respectively. Impairment of TAM receptor signaling and autophagy by
      anti-beta2 GPI aPL may allow subsequent TLR and inflammasome activity, leading to
      a robust inflammatory response.

PMID- 29342503
TI  - Molecular Basis for Dysregulated Activation of NKX2-5 in the Vascular Remodeling
      of Systemic Sclerosis.
AB  - OBJECTIVE: NKX2-5 is a homeobox transcription factor that is required for the
      formation of the heart and vessels during development, with significant postnatal
      down-regulation and reactivation in disease states, characterized by vascular
      remodeling. The purpose of this study was to investigate mechanisms that activate
      NKX2-5 expression in diseased vessels, such as systemic sclerosis (scleroderma;
      SSc)-associated pulmonary hypertension (PH), and to identify genetic variability
      that potentially underlies susceptibility to specific vascular complications.
      METHODS: We explored NKX2-5 expression in biopsy samples from patients with SSc
      associated PH and in pulmonary artery smooth muscle cells (PASMCs) from patients
      with scleroderma. Disease-associated putative functional single-nucleotide
      polymorphisms (SNPs) at the NKX2-5 locus were cloned and studied in reporter gene
      assays. SNP function was further examined through protein-DNA binding assays,
      chromatin immunoprecipitation assays, and RNA silencing analyses. RESULTS:
      Increased NKX2-5 expression in biopsy samples from patients with SSc-associated
      PH was localized to remodeled vessels and PASMCs. Meta-analysis of 2 independent
      scleroderma cohorts revealed an association of rs3131917 with scleroderma (P =
      0.029). We demonstrated that disease-associated SNPs are located in a novel
      functional enhancer, which increases NKX2-5 transcriptional activity through the
      binding of GATA-6, c-Jun, and myocyte-specific enhancer factor 2C. We also
      characterized an activator/coactivator transcription-enhancer factor domain 1
      (TEAD1)/Yes-associated protein 1 (YAP1) complex, which was bound at rs3095870,
      another functional SNP, with TEAD1 binding the risk allele and activating the
      transcription of NKX2-5. CONCLUSION: NKX2-5 is genetically associated with
      scleroderma, pulmonary hypertension, and fibrosis. Functional evidence revealed a
      regulatory mechanism that results in NKX2-5 transcriptional activation in PASMCs
      through the interaction of an upstream promoter and a novel downstream enhancer.
      This mechanism can act as a model for NKX2-5 activation in cardiovascular disease
      characterized by vascular remodeling.

PMID- 29342504
TI  - Polyarthralgias and Papulonodules in a 56-Year-Old Woman.

PMID- 29342505
TI  - Reply.

PMID- 29342506
TI  - Effects of a Dietary Approach to Stop Hypertension (DASH) Diet Intervention on
      Serum Uric Acid in African Americans With Hypertension.
AB  - OBJECTIVE: To examine whether partial replacement of a diet typical of the
      average American diet with Dietary Approaches to Stop Hypertension (DASH)-related
      foods in the home environment lowers the serum uric acid (UA) level in
      individuals with hypertension. METHODS: We conducted an ancillary study of a
      randomized trial of African American adults with controlled hypertension from an
      urban clinic. Participants were assigned to either a control group or an
      intervention (DASH-Plus) group. DASH-Plus participants received coach-directed
      dietary advice, assistance with purchasing DASH-related foods ($30/week), and
      home delivery of food via a community supermarket. Participants in the control
      group received a DASH diet brochure and a debit card account ($30/week) to
      purchase foods. Serum UA levels were measured at baseline and after 8 weeks.
      RESULTS: Of the original 123 randomized participants, 117 had available serum UA
      measurements. Seventy percent of the participants were women, the mean +/- SD age
      was 59 +/- 9.5 years, and the mean +/- SD serum UA level was 6.4 +/- 1.7 mg/dl.
      The DASH-Plus diet did not reduce serum UA levels compared with the control diet
      (difference in difference -0.01 mg/dl [95% confidence interval -0.39, 0.38]).
      However, there was a significant trend toward a greater reduction in the serum UA
      level in participants with higher baseline serum UA levels (P for trend = 0.008).
      Baseline changes in the serum UA level were inversely associated with changes in
      systolic blood pressure (P = 0.002), diastolic blood pressure (P = 0.001), and
      urinary sodium excretion (P = 0.05). CONCLUSION: Overall, in African American
      individuals, partial replacement of a typical diet with DASH foods did not lower
      serum UA levels compared with a control diet. However, there was a significant
      trend toward a greater reduction in serum UA levels in subjects with higher
      baseline serum UA levels. Furthermore, changes in serum UA levels were associated
      with known correlates, suggesting heterogeneity of effects in the treatment and
      control arms. Future pragmatic studies of consumption of the DASH diet to lower
      serum UA levels should optimize replacement strategies and enroll individuals
      with hyperuricemia or gout.

PMID- 29342508
TI  - Features, Treatment, and Outcomes of Macrophage Activation Syndrome in Childhood
      Onset Systemic Lupus Erythematosus.
AB  - OBJECTIVE: To describe the features and treatment of macrophage activation
      syndrome (MAS) in a single-center cohort of patients with childhood-onset
      systemic lupus erythematosus (SLE), and to compare childhood-onset SLE
      manifestations and outcomes between those with and those without MAS. METHODS: We
      included all patients with childhood-onset SLE followed up at The Hospital for
      Sick Children from 2002 to 2012, and identified those also diagnosed as having
      MAS. Demographic, clinical, and laboratory features of MAS and SLE, medication
      use, hospital and pediatric intensive care unit (PICU) admissions, as well as
      damage indices and mortality data were extracted from the Lupus database.
      Student's t-tests and Fisher's exact tests were used to compare continuous and
      categorical variables, respectively. We calculated incidence rate ratios of
      hospital and PICU admissions comparing patients with and those without MAS, using
      Poisson models. Kaplan-Meier survival analysis was used to examine the time to
      disease damage accrual. RESULTS: Of the 403 patients with childhood-onset SLE, 38
      (9%) had MAS. The majority (68%) had concomitant MAS and SLE diagnoses. Fever was
      the most common MAS clinical feature. The frequency of renal and central nervous
      system disease, hospital admissions, the average daily dose of steroids, and time
      to disease damage were similar between those with and those without MAS. We
      observed a higher mortality rate among those with MAS (5%) than those without MAS
      (0.2%) (P = 0.02). CONCLUSION: MAS was most likely to develop concomitantly with
      childhood-onset SLE diagnosis. The majority of the MAS patients were successfully
      treated with corticosteroids with no MAS relapses. Although the numbers were
      small, there was a higher risk of death associated with MAS compared to SLE
      without MAS.

PMID- 29342507
TI  - The Role of Autophagy in the Degradation of Misfolded HLA-B27 Heavy Chains.
AB  - OBJECTIVE: To determine whether autophagy is involved in the degradation of
      misfolded HLA-B27 in experimental spondyloarthritis. METHODS: Bone marrow-derived
      macrophages from HLA-B27/human beta2 -microglobulin (hbeta2 m)-transgenic rats
      were incubated in the presence or absence of interferon-gamma and proteasome or
      autophagy inhibitors. Immunoprecipitation, immunoblotting, and immunofluorescence
      analysis were used to measure HLA-B27 heavy chains and autophagy. Autophagy was
      induced using rapamycin. Macrophages from HLA-B7/hbeta2 m-transgenic and wild
      type rats were used as controls. RESULTS: HLA-B27-expressing macrophages showed
      phosphatidylethanolamine-conjugated microtubule-associated protein 1 light chain
      3B levels similar to those in both control groups, before and after manipulation
      of autophagy. Blocking autophagic flux with bafilomycin resulted in the
      accumulation of misfolded HLA-B27 dimers and oligomers as well as monomers, which
      was comparable with the results of blocking endoplasmic reticulum-associated
      degradation (ERAD) with the proteasome inhibitor bortezomib. HLA-B7 monomers also
      accumulated after blocking each degradation pathway. The ubiquitin-to-heavy chain
      ratio was 2-3-fold lower for HLA-B27 than for HLA-B7. Activation of autophagy
      with rapamycin rapidly eliminated ~50% of misfolded HLA-B27, while folded HLA-B27
      or HLA-B7 monomeric heavy chains were minimally affected. CONCLUSION: This study
      is the first to demonstrate that both autophagy and ERAD play roles in the
      elimination of excess HLA class I heavy chains expressed in transgenic rats. We
      observed no evidence that HLA-B27 expression modulated the autophagy pathway. Our
      results suggest that impaired ubiquitination of HLA-B27 may play a role in the
      accumulation of misfolded disulfide-linked dimers, the elimination of which can
      be enhanced by activation of autophagy. Manipulation of the autophagy pathway
      should be further investigated as a potential therapeutic target in
      spondyloarthritis.

PMID- 29342509
TI  - Influence of Explanatory Images on Risk Perceptions and Treatment Preference.
AB  - OBJECTIVE: The aim of this study was to examine whether providing patients with a
      series of balance scales (BS), depicting a reciprocal relationship between
      achieving disease control and increasing the risk of infection, influences
      treatment preference. METHODS: Participants were randomized to receive a
      description of a medication in which risk of infection was relayed using 1 of 4
      formats, including numbers only, numbers + icon array (IA), numbers + BS, or
      numbers + IA + BS (i.e., combination). We compared the likelihood of starting the
      medication across the 4 formats, and evaluated whether the influence of risk
      formats varied by numeracy and gist risk appraisals. RESULTS: The mean +/- SE
      likelihood of starting the medication was higher among participants randomized to
      the combination format (3.85 +/- 0.09) compared to those who viewed the BS (3.56
      +/- 0.09; P = 0.0222) or numbers-only formats (3.51 +/- 0.09; P = 0.0069).
      Viewing an IA alone was associated with a lower likelihood of starting the
      medication among participants lower in numeracy and endorsing a risk-avoidant
      noncompensatory gist risk appraisal. Conversely, viewing an IA (with or without
      the BS) was associated with a greater likelihood of starting the medication among
      patients with higher numeracy and compensatory risk appraisals. CONCLUSION:
      Adding explanatory images to IAs increases patient likelihood to take a
      medication in those with low numeracy and a noncompensatory gist risk appraisal.
      Explanatory images may be a feasible approach to improve willingness to try
      medication among subjects who are especially risk averse and believe that any
      risk is unacceptable.

PMID- 29342511
TI  - Sign, language, and gesture in the brain: Some comments.
AB  - In contrast with two widely held and contradictory views - that sign languages of
      deaf people are "just gestures," or that sign languages are "just like spoken
      languages" - the view from sign linguistics and developmental research in
      cognition presented by Goldin-Meadow & Brentari (G-M&B) indicates a more complex
      picture. We propose that neuroscience research suggests that a similar approach
      needs to be taken and offer some examples from research on the brain bases of
      sign language perception.

PMID- 29342512
TI  - Building a single proposition from imagistic and categorical components.
AB  - Bimodal bilingual language provides further evidence for the viewpoint advocated
      by Goldin-Meadow & Brentari (G-M&B) that sign, speech, and gesture work together
      to create a single proposition, illustrating the potential in each set of
      articulators for both imagistic and categorical components. Recent advances in
      formal semantics provide a framework for incorporating both imagistic and
      categorical components into a single compositional system.

PMID- 29342510
TI  - Validation of the Social Appearance Anxiety Scale in Patients With Systemic
      Sclerosis: A Scleroderma Patient-Centered Intervention Network Cohort Study.
AB  - OBJECTIVE: Systemic sclerosis (SSc) is an autoimmune disease that can cause
      disfiguring changes in appearance. This study examined the structural validity,
      internal consistency reliability, convergent validity, and measurement
      equivalence of the Social Appearance Anxiety Scale (SAAS) across SSc disease
      subtypes. METHODS: Patients enrolled in the Scleroderma Patient-centered
      Intervention Network Cohort completed the SAAS and measures of appearance-related
      concerns and psychological distress. Confirmatory factor analysis (CFA) was used
      to examine the structural validity of the SAAS. Multiple-group CFA was used to
      determine whether SAAS scores can be compared across patients with limited and
      diffuse disease subtypes. Cronbach's alpha was used to examine internal
      consistency reliability. Correlations of SAAS scores with measures of body image
      dissatisfaction, fear of negative evaluation, social anxiety, and depression were
      used to examine convergent validity. SAAS scores were hypothesized to be
      positively associated with all convergent validity measures, with correlations
      significant and moderate to large in size. RESULTS: A total of 938 patients with
      SSc were included. CFA supported a 1-factor structure (Comparative Fit Index
      0.92, Standardized Root Mean Residual 0.04, and Root Mean Square Error of
      Approximation 0.08), and multiple-group CFA indicated that the scalar invariance
      model best fit the data. Internal consistency reliability was good in the total
      sample (alpha = 0.96) and in disease subgroups. Overall, evidence of convergent
      validity was found with measures of body image dissatisfaction, fear of negative
      evaluation, social anxiety, and depression. CONCLUSION: The SAAS can be reliably
      and validly used to assess fear of appearance evaluation in patients with SSc,
      and SAAS scores can be meaningfully compared across disease subtypes.

PMID- 29342513
TI  - Is it language (yet)? The allure of the gesture-language binary.
AB  - Goldin-Meadow & Brentari (G-M&B) challenge the traditional separation between
      gestural and categorical language by modality, but they retain a binary
      distinction. However, multiple dimensions, particularly discreteness and
      combinatoriality, better carve up the range of linguistic and nonlinguistic human
      communication. Investigating transformation over time along these dimensions will
      reveal how the nature of language reflects human minds, rather than the world to
      which language refers.

PMID- 29342514
TI  - Perspectives on gesture from autism spectrum disorder: Alterations in timing and
      function.
AB  - The target article highlights the utility of new technology to study sign
      language and gesture. Research in special populations - specifically, individuals
      with autism spectrum disorder, ASD - may further illuminate sign/gesture
      similarities and differences and lead to a deeper understanding of the mechanisms
      of growth and change. Even verbally fluent speakers with ASD display distinctive
      qualities in sign and gesture.

PMID- 29342515
TI  - Emoticons in text may function like gestures in spoken or signed communication.
AB  - We draw parallels between emoticons in textual communication and gesture in
      signed language with respect to the interdependence of codes by describing two
      contexts under which the behavior of emoticons in textual communication resembles
      that of gesture in speech. Generalizing from those findings, we propose that
      gesture is likely characterized by a nuanced interdependence with language
      whether signed, spoken or texted.

PMID- 29342516
TI  - How to distinguish gesture from sign: New technology is not the answer.
AB  - Linguistic and psycholinguistic tests will be more useful than motion capture
      technology in calibrating the borders between sign and gesture. The analogy
      between motion capture (mocap) technology and the spectrograph is flawed because
      only vocal articulators are hidden. Although information about gradience and
      variability will be obtained, the technology provides less information about
      linguistic constraints and categories. Better models are needed to account for
      differences between co-speech and co-sign gesture (e.g., different degrees of
      optionality, existence of beat gestures).

PMID- 29342517
TI  - Why space is not one-dimensional: Location may be categorical and imagistic.
AB  - In our commentary, we raise concerns with the idea that location should be
      considered a gestural component of sign languages. We argue that psycholinguistic
      studies provide evidence for location as a "categorical" element of signs. More
      generally, we propose that the use of space in sign languages comes in many
      flavours and may be both categorical and imagistic. In their target article,
      Goldin-Meadow & Brentari (G-M&B) discuss several observations suggesting that the
      use of space is imagistic and may not form part of the categorical properties of
      sign languages. Specifically, they point out that (1) the number of locations
      toward which agreeing verbs can be directed is not part of a discrete set, (2)
      event descriptions by users of different sign languages and hearing nonsigners
      exhibit marked similarities in the use of space, and (3) location as a
      phonological parameter is not categorically perceived by native signers. It
      should be noted that G-M&B acknowledge that categorical properties of location
      and movement may simply not have been captured yet because the proper
      investigative tools are not yet readily available.

PMID- 29342518
TI  - Understanding gesture in sign and speech: Perspectives from theory of mind,
      bilingualism, and acting.
AB  - In their article, Goldin-Meadow & Brentari (G-M&B) assert that researchers must
      differentiate between sign/speech and gesture. We propose that this distinction
      may be useful if situated within a two-systems approach to theory of mind (ToM)
      and discuss how drawing upon perspectives from bilingualism and acting can help
      us understand the role of gesture in spoken/sign language.

PMID- 29342519
TI  - Languages as semiotically heterogenous systems.
AB  - The target article is consistent with seeing languages as semiotically
      heterogenous, using categorial, depictive, and analogic semiotic signs.
      "Gesture," used in the target article, is shown to be vague and not useful.
      Kendon's view, criticised in the target, is restated. His proposal for
      comparative semiotic analyses of how visible bodily action is used in utterance
      production is reexplained.

PMID- 29342520
TI  - Current and future methodologies for quantitative analysis of information
      transfer in sign language and gesture data.
AB  - State-of-the-art methods of analysis of video data now include motion capture and
      optical flow from video recordings. These techniques allow for biological
      differentiation between visual communication and noncommunicative motion,
      enabling further inquiry into neural bases of communication. The requirements for
      additional noninvasive methods of data collection and automatic analysis of
      natural gesture and sign language are discussed.

PMID- 29342521
TI  - An evolutionary approach to sign language emergence: From state to process.
AB  - Understanding the relationship between gesture, sign, and speech offers a
      valuable tool for investigating how language emerges from a nonlinguistic state.
      We propose that the focus on linguistic status is problematic, and a shift to
      focus on the processes that shape these systems serves to explain the
      relationship between them and contributes to the central question of how language
      evolves.

PMID- 29342522
TI  - Language readiness and learning among deaf children.
AB  - We applaud Goldin-Meadow & Brentari's (G-M&B's) significant efforts to consider
      the linkages between sign, gesture, and language. Research on deaf children and
      sign language acquisition can broaden the G-M&B approach by considering how
      language readiness is also a social phenomenon and that distinctions between
      imagistic and categorical formats rely on language practices and contexts.

PMID- 29342523
TI  - Same or different: Common pathways of behavioral biomarkers in infants and
      children with neurodevelopmental disorders?
AB  - The extent to which early motor patterns represent antecedents to later
      communicative functions, and the emergence of gesture and/or sign as potential
      communicative acts in neurodevelopmental disorders (NDDs), are research questions
      that have received recent attention. It is important to keep in mind that
      different NDDs have different neurological underpinnings, with correspondingly
      different implications for their conceptualization, detection, and treatment.

PMID- 29342524
TI  - Are gesture and speech mismatches produced by an integrated gesture-speech
      system? A more dynamically embodied perspective is needed for understanding
      gesture-related learning.
AB  - We observe a tension in the target article as it stresses an integrated gesture
      speech system that can nevertheless consist of contradictory representational
      states, which are reflected by mismatches in gesture and speech or sign. Beyond
      problems of coherence, this prevents furthering our understanding of gesture
      related learning. As a possible antidote, we invite a more dynamically embodied
      perspective to the stage.

PMID- 29342525
TI  - Toward true integration.
AB  - Whether in sign or speech, language is more integrative than the target article
      suggests. A more integrative view embraces not only sign/speech and co
      sign/speech gesture, but also indicative gestures irrespective of modality, and
      locations along with movements in the signed modality, as suggested by both
      linguistic acquisition and pathologies. An extended integrative view also proves
      advantageous in terms of conceptual coherence.

PMID- 29342526
TI  - Vocal laughter punctuates speech and manual signing: Novel evidence for similar
      linguistic and neurological mechanisms.
AB  - Vocal laughter fills conversations between speakers with normal hearing and
      between deaf users of American Sign Language, but laughter rarely intrudes on the
      phrase structure of spoken or signed conversation, being akin to punctuation in
      written text. This punctuation effect indicates that language, whether vocal or
      signed, is dominant over laughter, and that speech and manual signing involve
      similar mechanisms.

PMID- 29342527
TI  - Iconic enrichments: Signs vs. gestures.
AB  - Semantic work on sign language iconicity suggests, as do Goldin-Meadow & Brentari
      (G-M&B) in their target article, that "sign should be compared with speech-plus
      gesture, not speech alone" (sect. 7.1). One key question is whether speech-plus
      gesture and sign-with-iconicity really display the same expressive resources.
      This need not be the case, because gestural enrichments are typically not at
      issue, whereas iconic enrichments in sign language can often be at-issue. Future
      research should thus focus on the "projection" properties of different sorts of
      iconic enrichment in both modalities.

PMID- 29342528
TI  - Gestures can create diagrams (that are neither imagistic nor analog).
AB  - The claim that gesture is primarily imagistic, analog, and holistic is challenged
      by the presence of abstract diagrammatic gestures, here points and lines, that
      represent point-like and line-like concepts and are integrated into larger
      constituents.

PMID- 29342529
TI  - Gesture and language: Distinct subsystem of an integrated whole.
AB  - The commentaries have led us to entertain expansions of our paradigm to include
      new theoretical questions, new criteria for what counts as a gesture, and new
      data and populations to study. The expansions further reinforce the approach we
      took in the target article: namely, that linguistic and gestural components are
      two distinct yet integral sides of communication, which need to be studied
      together.

PMID- 29342530
TI  - Pros and cons of blurring gesture-language lines: An evolutionary linguistic
      perspective.
AB  - The target article's emphasis on distinguishing sign from gesture may resolve one
      important objection to gesture-first theories of language evolution. However,
      this approach risks undervaluing the gradual progression from nonlanguage to
      language over hominin evolution, and in emerging sign systems today. I call for
      less emphasis on drawing boundaries and more emphasis on understanding the
      processes of change.

PMID- 29342531
TI  - Good things come in threes: Communicative acts comprise linguistic, imagistic,
      and modifying components.
AB  - Gesture and sign form an integrated communication system, as do gesture and
      speech. Communicative acts in both systems combine categorical linguistic (words
      or signs) with imagistic (gestures) components. Additionally, both sign and
      speech can employ modifying components that convey iconic information tied to a
      linguistic base morpheme. An accurate analysis of communicative acts must take
      this third category into account.

PMID- 29342532
TI  - The influence of communication mode on written language processing and beyond.
AB  - Empirical evidence suggests a broad impact of communication mode on cognition at
      large, beyond language processing. Using a sign language since infancy might
      shape the representation of words and other linguistic stimuli - for example,
      incorporating in it the movements and signs used to express them. Once integrated
      into linguistic representations, this visuo-motor content can affect deaf
      signers' linguistic and cognitive processing.

PMID- 29342533
TI  - Where does (sign) language begin?
AB  - Goldin-Meadow & Brentari (G-M&B) outline several criteria for delineating the
      boundaries between (discrete) signs and (continuous) gestures. However, the
      complex links between linguistics forms and their phonetic realizations defy such
      heuristics. A systematic exploration of language structure by mouth and by hand
      may help get us closer to answering the important challenge outlined in this
      target article.

PMID- 29342534
TI  - The physiognomic unity of sign, word, and gesture.
AB  - Goldin-Meadow & Brentari (G-M&B) are implicitly going against the dominant
      paradigm in language research, namely, the "speech as written language" metaphor
      that portrays vocal sounds and bodily signs as means of delivering stable word
      meanings. We argue that Heinz Werner's classical research on the physiognomic
      properties of language supports and complements their view of sign and gesture as
      a unified system.

PMID- 29342535
TI  - What is a gesture? A lesson from comparative gesture research.
AB  - Research into nonhuman primates' gestures is often limited by the lack of clear
      criteria to define a gesture and by studying gestures separately from other
      communicative means. Despite the fundamental differences between the gestural
      communication of humans and other primates, I argue that sign language research
      might benefit from the lessons learned from these drawbacks and the current
      developments in primate communication research.

PMID- 29342536
TI  - Why would the discovery of gestures produced by signers jeopardize the
      experimental finding of gesture-speech mismatch?
AB  - Mismatch occurs when there is a discrepancy between produced gestures and co
      occurring speech. In this commentary, I explore why research on mismatch might be
      called into question by changing views of what constitutes a gesture. I argue
      that the experimental procedure for producing mismatch, through its coding
      methods, is blind to the tight temporal coordination of gesture and affiliated
      talk.

PMID- 29342537
TI  - The categorical role of structurally iconic signs.
AB  - Goldin-Meadow & Brentari (G-M&B) argue that, for sign language users, gesture -
      in contrast to linguistic sign - is iconic, highly variable, and similar to
      spoken language co-speech gesture. We discuss two examples (telicity and absolute
      gradable adjectives) that challenge the use of these criteria for distinguishing
      sign from gesture.

PMID- 29342538
TI  - Gesture or sign? A categorization problem.
AB  - Goldin-Meadow & Brentari (G-M&B) rely on a formalist approach to language,
      leading them to seek objective criteria by which to distinguish language and
      gesture. This results in the assumption that gradient aspects of signs are
      gesture. Usage-based theories challenge this view, maintaining that all
      linguistic units exhibit gradience. Instead, we propose that the distinction
      between language and gesture is a categorization problem.

PMID- 29342539
TI  - Pragmatic prospection emphasizes utility of predicting rather than mere
      predictability.
AB  - Contrary to one assumption of CLASH, we suggest that colder rather than warm
      climates are the harsh, unpredictable ones, thus requiring greater self-control.
      We propose shifting emphasis from predictability to utility of prediction.
      Northern climates may be less predictable than tropical ones, making predictions
      and planning far more important, insofar as they can prevent fatalities and
      promote other pragmatic benefits.

PMID- 29342540
TI  - A climate of confusion.
AB  - I identify two confusions and omissions in the target article. Confusion arises
      from failure to distinguish between a genetically transmitted adaptation and a
      conditional response to the environment, and from the elision of individual and
      societal adaptations. Despite points of similarity, there is no mention of
      Rushton's controversial theory of the climatic basis of race differences in
      violent crime. Sex differences are also ignored.

PMID- 29342541
TI  - The CLASH model lacks evolutionary and archeological support.
AB  - Data from archaeology and paleoanthropology directly challenge the validity of
      the basic assumptions of the CLASH model. By not incorporating a "deep time"
      perspective, the hypothesis lacks the evolutionary baseline the authors seek to
      infer in validating the model.

PMID- 29342542
TI  - Dimensions of environmental risk are unique theoretical constructs.
AB  - Life history theory serves as the foundation for the CLimate, Aggression, and
      Self-control in Humans (CLASH) model of aggression. However, this model embodies
      several misunderstandings of life history constructs and principles. The CLASH
      model does not recognize that environmental harshness and environmental
      unpredictability are unique theoretical constructs, rendering predictions and
      implications from the model suspect.

PMID- 29342543
TI  - Using foresight to prioritise the present.
AB  - Planning for the future may encourage apparently "impulsive" behaviour when the
      future is anticipated to be bleak. Thus, a seeming failure of self-control in
      reactive violence could be caused not by a disinclination to plan ahead, but by
      virtue of this ability. Furthermore, we point to empirical and theoretical
      shortcomings in the authors' case, such as a failure to distinguish proximate and
      ultimate explanations.

PMID- 29342544
TI  - CLASH's life history foundations.
AB  - We recommend extending CLASH by incorporating two evolutionary accounts of the
      shift toward fast life histories under harsh, unpredictable conditions. These
      accounts, if integrated with CLASH, make different predictions about the
      distributions of aggression and violence within and between societies. We discuss
      these predictions and propose ways of testing them.

PMID- 29342545
TI  - Does distance from the equator predict self-control? Lessons from the Human
      Penguin Project.
AB  - We comment on the proposition "that lower temperatures and especially greater
      seasonal variation in temperature call for individuals and societies to adopt ...
      a greater degree of self-control" (Van Lange et al., sect. 3, para. 4) for which
      we cannot find empirical support in a large data set with data-driven analyses.
      After providing greater nuance in our theoretical review, we suggest that Van
      Lange et al. revisit their model with an eye toward the social determinants of
      self-control.

PMID- 29342546
TI  - More than just climate: Income inequality and sex ratio are better predictors of
      cross-cultural variations in aggression.
AB  - Van Lange et al. argue that variations in climate explain cross-societal
      variations in violence. We suggest that any approach seeking to understand cross
      cultural variation in human behavior via an ecological framework must consider a
      wider array of ecological variables, and we find that income inequality and sex
      ratio are better predictors than climate of cross-societal variations in
      violence.

PMID- 29342547
TI  - Climate is not a good candidate to account for variations in aggression and
      violence across space and time.
AB  - We agree with Van Lange et al. that climate is likely to affect individuals'
      social behavior in many ways. However, we suspect that its impact on physiology
      and psychology is so remote that its predictive power disintegrates almost
      completely through the causal chain underlying aggression and violence.

PMID- 29342548
TI  - Postcolonial geography confounds latitudinal trends in observed aggression and
      violence.
AB  - To support their hypothesis, the authors point to an inverse correlation between
      latitude and the incidence of civil conflict and crime. This observation cannot
      be accepted as evidence for the hypothesis, because of a weighty confounding
      variable: the historical geography of colonialism and its effects on the
      fragility of nations.

PMID- 29342549
TI  - The role of adolescence in geographic variation in violent aggression.
AB  - In explaining variation in violent aggression across populations, the age
      structures of those populations must be considered. Adolescents between the ages
      of 15 and 25 are disproportionately responsible for violent aggression in every
      society, and increases in violence tend to follow population "youth bulges."
      Large numbers of adolescents in equatorial regions may account for observed
      relationships between geography and violence.

PMID- 29342550
TI  - The paradoxical effect of climate on time perspective considering resource
      accumulation.
AB  - Considering purely climate, southern countries are less harsh and more
      predictable than northern countries. From a historical perspective, freezing
      winters resulting in fewer available resources contribute to the development of
      strong future orientation. The paradox is that future orientation contributes to
      accumulation of resources in the long run, making individuals' immediate living
      conditions less harsh, leading to slower life strategies.

PMID- 29342551
TI  - The CLASH model in broader life history context.
AB  - In this commentary, we address two questions: (1) Is the drive in many young men
      to gain status and amass resources, which frequently entails direct competition
      with members of outgroups, one of the key variables underlying the CLASH model?
      (2) Why is there so much variation in reactive aggression/violence between people
      living in the same environment?

PMID- 29342552
TI  - An alternative interpretation of climate data: Intelligence.
AB  - The CLASH model proposed in the target article is plausible but less than
      parsimonious. I suggest that statistical analysis probably would find slower life
      history strategy, greater focus on the future, and greater self-control to be
      highly correlated and perhaps unifactorial, because they are all manifestations
      of a single underlying variable, namely, intelligence. I suggest how intelligence
      as a state variable plausibly could explain the differences observed by the
      authors.

PMID- 29342553
TI  - Sociocultural discourse in science: Flawed assumptions and bias in the CLASH
      model.
AB  - In this commentary, we contest Van Lange and colleagues' central claim that
      "countries closer to the equator are generally more violent." We point to the
      lack of credible empirical evidence for this assertion and suggest that the CLASH
      model uses the language of science to lend false credibility to a problematic
      sociocultural discourse.

PMID- 29342554
TI  - Bullying when it's hot? The CLASH model and climatic influences on bullying.
AB  - A novel predictor of bullying may be underlying regional weather conditions
      (i.e., climate). Bullying data support the CLASH model of aggression by
      suggesting that climate may moderate the forms and severity of bullying, as well
      as predict its prevalence across countries. Furthermore, bullying data also
      suggest that the CLASH model may apply to forms of aggression beyond reactive
      aggression.

PMID- 29342555
TI  - Hell on earth? Equatorial peaks of heat, poverty, and aggression.
AB  - Van Lange et al.'s global CLASH model overemphasizes climatic origins and
      underemphasizes economic origins of aggression. Our 167-country analysis of
      latitudinal gradients of heat, poverty, and aggression finds that heat-induced
      aggression is mediated by poverty and that heat tempers rather than fuels poverty
      induced aggression. More importantly, the CLASH model hints at latitudinal,
      equatorial, and hemispheric upgradings of climato-economic modeling of human
      behavior.

PMID- 29342556
TI  - Culture matters for life history trade-offs.
AB  - Van Lange et al. add important life history perspectives to understanding
      violence. However, direct links between climate and violence are unlikely because
      cultural institutions modify human responses. Examples are given from the Bushmen
      of the Kalahari and Enga of Papua New Guinea. The correlations identified may
      occur because many countries closer to the equator are caught in the gap between
      the demise of traditional cultural institutions and the rise of modern forms of
      governance.

PMID- 29342557
TI  - Reply to Van Lange et al.: Proximate and ultimate distinctions must be made to
      the CLASH model.
AB  - Transcending reviewed proximate theories, Van Lange et al.'s CLASH model attempts
      to ultimately explain the poleward declension of aggression and violence.
      Seasonal cold is causal, but, we contend, principally as an ecologically relevant
      evolutionary pressure. We further argue that futurity and restraint are life
      history variables, and that Life History Theory evolutionarily explains the
      biogeography of aggression and violence as strategic adaptation.

PMID- 29342558
TI  - Where the psychological adaptations hit the ecological road.
AB  - We argue that the target authors focus too much on adaptive behavioral responses
      and not enough on actual psychological adaptations. We suggest the Dark Triad
      traits may represent facultative, psychological adaptations sensitive to seasonal
      variance and food shortages. We document that shorter distances from the equator
      are linked to higher national narcissism levels, whereas longer distances are
      associated with higher national-level machiavellianism. Dark Triad traits may
      serve as critical survival mechanisms when prioritizing oneself over and/or at
      the cost of others.

PMID- 29342559
TI  - Stuck in the heat or stuck in the hierarchy? Power relations explain regional
      variations in violence.
AB  - We contend that an ecological account of violence and aggression requires
      consideration of societal and cultural settings. Focusing on hierarchical
      relations, we argue countries with higher (vs. lower) power distance are, on
      average, located closer to the equator, have more challenging climates (e.g.,
      higher temperature; lower temperature variation), and have a greater prevalence
      of violence and aggression (e.g., higher homicide rates).

PMID- 29342560
TI  - Why the CLASH model is an unconvincing evolutionary theory of crime.
AB  - The CLASH model is not convincing for two reasons. First, it ignores prior
      research proposing very similar ideas in a more compelling fashion. Second, it
      dismisses the role of genetic factors in shaping criminal propensities across
      population groups, opting for a facultative view of life history evolution that
      does not seem to square with current evidence.

PMID- 29342561
TI  - The importance of being explicit.
AB  - Van Lange et al. propose that climate affects violence via its effects on life
      history. That much is reasonable (and not novel), but their theory lacks causal
      specificity. Their foundational claim of an association between heat and violence
      is not well documented, and several findings that the authors themselves cite
      seem inconsistent with their model, rather than supportive.

PMID- 29342562
TI  - Warm coffee, sunny days, and prosocial behavior.
AB  - This commentary discusses the research finding that warmer temperatures are
      associated with more prosocial outcomes. It calls for future research and theory
      on climate-related variables and social behavior to allow for both positive and
      negative emotional and behavioral responses to warmer temperatures.

PMID- 29342563
TI  - Russian data refute the CLASH model.
AB  - We examined the CLASH model using the data on climate and violence from the
      Russian Federation. The Russian Federation is a huge country with dramatic
      climatic differences between regions. Our results are absolutely inconsistent
      with the model. We consider there are a range of climates in which the human
      organism functions optimally. Deviations from the range cause impulsiveness and
      aggression.

PMID- 29342564
TI  - The role of climate in human aggression and violence: Towards a broader
      conception.
AB  - The psychological processes that predict aggressive behaviour are also typically
      associated with violent self-harm (e.g., poor self-control). Yet, although human
      violence (towards others) appears to increase with proximity to the equator,
      suicide rates tend to decrease. In the light of this empirical puzzle, I argue
      that Van Lange et al.'s CLASH model would benefit from a broader
      conceptualization of human aggression.

PMID- 29342565
TI  - The Logic of Climate and Culture: Evolutionary and Psychological Aspects of
      CLASH.
AB  - A total of 80 authors working in a variety of scientific disciplines commented on
      the theoretical model of CLimate, Aggression, and Self-control in Humans (CLASH).
      The commentaries cover a wide range of issues, including the logic and
      assumptions of CLASH, the evidence in support of CLASH, and other possible causes
      of aggression and violence (e.g., wealth, income inequality, political
      circumstances, historic circumstances, pathogen stress). Some commentaries also
      provide data relevant to CLASH. Here we clarify the logic and assumptions of
      CLASH and discusses its extensions and boundary conditions. We also offer
      suggestions for future research. Regardless of whether none, some, or all of
      CLASH is found to be true, we hope it will stimulate future research on the link
      between climate and human behavior. Climate is one of the most presing issues of
      our time.

PMID- 29342566
TI  - Aggression, predictability of the environment, and self-regulation:
      Reconciliation with animal research.
AB  - Apparently inconsistent with the CLASH model, animal research relates predictable
      environments to rigid routine behaviors and aggression. However, our work on
      evolutionary and neural adaptations to (un)predictable environments may be able
      to reconcile the CLASH model with the animal research, but also suggests
      complexities beyond the dichotomous approach of CLASH.

PMID- 29342567
TI  - Inconsistent with the data: Support for the CLASH model depends on the wrong kind
      of latitude.
AB  - We argue that the CLASH model makes a number of questionable assumptions about
      the harshness and unpredictability of low-latitude environments, calling into
      question the life history strategy approach used, and that it is inconsistent
      with more nuanced global patterns of violence. We suggest an alternative account
      for less violence at high latitudes, based on a greater need for cooperation.

PMID- 29342568
TI  - Mapping multiple drivers of human obesity.
AB  - The insurance hypothesis is a reasonable explanation for the current obesity
      epidemic. One alternative explanation is that the marketing of high-sugar foods,
      especially sugar-sweetened beverages, drives the rise in obesity. Another
      prominent hypothesis is that obesity spreads through social influence. We offer a
      framework for estimating the extent to which these different models explain the
      rise in obesity.

PMID- 29342569
TI  - Eating and body image: Does food insecurity make us feel thinner?
AB  - Body image distortions are common in healthy individuals and a central aspect of
      serious clinical conditions, such as eating disorders. This commentary explores
      the potential implications of body image and its distortions for the insurance
      hypothesis. In particular, we speculate that body image may be an intervening
      variable mediating the relationship between perceived food scarcity and eating
      behavior.

PMID- 29342570
TI  - Expanding the insurance hypothesis of obesity with physiological cues.
AB  - Food insecurity relates to fat storage, but cannot explain fat storage in excess
      of levels optimal for buffering - that is, obesity. However, factors related to
      food unpredictability in the past, including stress, disease, micronutrient
      content of food, and physical activity, may cue physiological processes that
      change intake or fat deposition even in the absence of actual food
      unpredictability.

PMID- 29342571
TI  - Epidemiological foundations for the insurance hypothesis: Methodological
      considerations.
AB  - Nettle et al. evaluate evidence for the insurance hypothesis, which links obesity
      with the perception of food scarcity. Epidemiological findings in this area have
      generally been weak and inconsistent. The present commentary examines three key
      methodological issues arising from the literature on the association between
      obesity and the perception of food scarcity in humans, with suggestions for
      future epidemiological research.

PMID- 29342572
TI  - The life history model of the insurance hypothesis.
AB  - Nettle et al.'s explanation based on the insurance hypothesis applies only to the
      association between food insecurity and body weight among adult women, but not to
      the results about there being no such associations among adult men and children.
      These results may be best understood when the insurance hypothesis is integrated
      with the life history model.

PMID- 29342573
TI  - Episodic memory as an explanation for the insurance hypothesis in obesity.
AB  - In evaluating the insurance hypothesis as an explanation for obesity, we propose
      one missing piece of the puzzle. Our suggested explanation for why individuals
      report food insecurity is that an individual may have an impaired episodic
      ability to plan for the future.

PMID- 29342574
TI  - Toward a mechanistic understanding of the impact of food insecurity on obesity.
AB  - Nettle et al. provide a useful but incomplete analysis of the drivers of obesity.
      In this commentary, we argue that a dual-motives conceptualization of self
      control, together with insights from the psychology of (perceived and actual)
      scarcity, might help advance a more fine-grained mechanistic understanding of the
      observed association between food insecurity and obesity.

PMID- 29342575
TI  - Appraising food insecurity.
AB  - This commentary focuses on the mechanisms underlying the appraisal of food
      insecurity. I first describe what appraisal is and why it plays a major role in
      explaining how different individuals consider food supply as more or less secure.
      I then describe the potential reciprocal links between appraisal and obesity,
      based on the well-documented evidence that obesity can cause cognitive deficits.

PMID- 29342576
TI  - Implicit attitudes, eating behavior, and the development of obesity.
AB  - Nettle et al. describe increasing food intake (relative to energy expenditure) in
      response to food insecurity as a key contributor to obesity. I argue that a
      variety of implicit psychological mechanisms underlie this process to contribute
      to weight gain. The biobehavioral pathways and the social nature of food
      selection discussed here are importantly related to food selection and obesity.

PMID- 29342577
TI  - A life-history theory perspective on obesity.
AB  - We extend Nettle et al.'s insurance hypothesis (IH) argument, drawing upon life
      history theory (LHT), a developmental evolutionary perspective that documents
      downstream consequences of early-life exposure to unpredictable environments. We
      discuss novel evidence consistent with both IH and LHT, suggesting that early
      life exposure to unpredictable environments is associated with reduced engagement
      in weight management behaviors and a greater probability of adulthood obesity.

PMID- 29342578
TI  - Potential psychological accounts for the relation between food insecurity and
      body overweight.
AB  - We suggest two psychological mechanisms, temporal discounting and feeling of
      resource scarcity, for explaining the relation between food insecurity and body
      overweight. We demonstrate how Nettle et al.'s findings could be explained, post
      hoc, by each of these accounts, suggesting that their data are not rich enough to
      allow identification of mechanisms that underlie food insecurity and overweight
      relationship.

PMID- 29342579
TI  - Predicting human adiposity - sometimes - with food insecurity: Broaden the model
      for better accuracy.
AB  - The target article explores the role of food insecurity as a contemporary risk
      factor for human overweight and obesity. The authors provide conditional support
      for the insurance hypothesis among adult women from high-income countries. We
      consider the potential contribution of additional factors in producing variation
      in adiposity patterns between species and across human contexts.

PMID- 29342580
TI  - Social nature of eating could explain missing link between food insecurity and
      childhood obesity.
AB  - We suggest that social factors are key to explain the missing link between food
      insecurity and obesity in children. Parents and public institutions are
      children's nutritional gatekeepers. They protect children from food insecurity by
      trimming down their consumption or by institutional support. To gauge children's
      food insecurity, evaluations across the different nutritional gatekeepers need to
      be integrated.

PMID- 29342581
TI  - A game theory appraisal of the insurance hypothesis: Specific polymorphisms in
      the energy homeostasis network as imprints of a successful minimax strategy.
AB  - The existence of specific polymorphisms in genes of key hormones of the energy
      homeostasis network that have been shown to predispose to obesity and the so
      called metabolic syndrome provides further biological support for the proposed
      insurance hypothesis. In a broader sense, such polymorphisms can be understood as
      biological imprints of an evolutionarily successful minimax strategy employed by
      ancient Homo sapiens subpopulations in a one-player game against nature.

PMID- 29342582
TI  - Towards a behavioural ecology of obesity.
AB  - Addressing the obesity epidemic depends on a holistic understanding of the
      reasons that people become and maintain excessive fat. Theories about the causes
      of obesity usually focus proximately or evoke evolutionary mismatches, with
      minimal clinical value. There is potential for substantial progress by adapting
      strategic body mass regulation models from evolutionary ecology to human obesity
      by assessing the role of information.

PMID- 29342583
TI  - Anti-fat discrimination in marriage more clearly explains the poverty-obesity
      paradox.
AB  - The target article proposes the insurance hypothesis as an explanation for higher
      levels of obesity among food-insecure women living in high-income countries. An
      alternative hypothesis based on anti-fat discrimination in marriage can also
      account for such correlations between poverty and obesity and is more consistent
      with finer-grained analyses by marital status, gender, and age.

PMID- 29342584
TI  - Committed to the insurance hypothesis of obesity.
AB  - Can ideas about the regulation of body mass in birds be used to explain the
      breakdown of regulation associated with obesity and anorexia in humans? There is
      no evidence to think so. Medicine can always benefit from the application of
      evolutionary ecology ideas, but we must be prepared to dismiss these ideas when
      they just do not fit the data.

PMID- 29342585
TI  - "It's a bit more complicated than that": A broader perspective on determinants of
      obesity.
AB  - The insurance hypothesis does not address important factors known to contribute
      to obesity levels in all persons, not just adult women in the industrialized
      world. These include psychological determinants of eating behaviours, the decline
      in physical activity leading to a negative energy balance, the dense built
      environment, pervasive food marketing, and the increased availability of energy
      dense, nutrient-poor food.

PMID- 29342586
TI  - Anorexia: A perverse effect of attempting to control the starvation response.
AB  - Starvation arouses evolved protective mechanisms including binge eating and
      increased metabolic efficiency and fat storage. When aroused by dieting, the
      experiences of out-of-control eating, increased appetite, and increased fat
      storage arouse greater fears of obesity, spurring renewed attempts to restrict
      intake severely. The resulting positive feedback cycle escalates into bulimia for
      many, and anorexia in a few.

PMID- 29342587
TI  - Obesity as self-regulation failure: A "disease of affluence" that selectively
      hits the less affluent?
AB  - An effect of the long-term cycle of industrial and post-industrial global
      development is the increasingly generalized access to abundant and diversified
      food sources. This poses a substantial problem of self-regulation that mainly
      affects the less affluent and whose failures may play an important role in the
      explanation of the increasing social incidence of overweight and obesity
      problems.

PMID- 29342588
TI  - Obesity is not just elevated adiposity, it is also a state of metabolic
      perturbation.
AB  - Nettle et al. miss the crucial difference between adaptive models of storing
      energy and explanations for the pathological metabolic state of obesity. I
      suggest that the association of food insecurity with obesity in women from
      industrialized settings is most likely due to reverse causation: Poverty reduces
      agency to resist obesogenic foods, and this scenario is compounded by
      perturbations of insulin metabolism stemming from high adiposity and lipogenic
      diets.

PMID- 29342589
TI  - Using food insecurity in health prevention to promote consumer's embodied self
      regulation.
AB  - Health messages designed to address obesity are typically focused on the long
      term benefits of eating healthy food. However, according to the insurance
      hypothesis, obese people are food insecure, and this causes them to be overly
      concerned about short-term consumption. As such, it is necessary to rethink
      public health messaging and consider how to reduce short-term insecurity by
      eating healthy food.

PMID- 29342590
TI  - Household-level financial uncertainty could be the primary driver of the global
      obesity epidemic.
AB  - Evidence has accumulated in support of the notion that changes in household-level
      financial uncertainty (or "economic insecurity") may be an important fundamental
      cause of the global obesity epidemic. The timing and spatial/demographic
      incidence of the obesity epidemic suggest that economic policies aimed at
      expanding economic freedom may have inadvertently shifted risk to households,
      thereby generating a costly public health problem.

PMID- 29342591
TI  - Children respond to food restriction by increasing food consumption.
AB  - Consistent with the insurance hypothesis, research shows that when children
      experience restricted access to food, they display increased intake when
      restrictions are lifted. This effect appears more robust for girls compared to
      boys, and for children with lower levels of inhibitory control. The insurance
      hypothesis has potentially important implications for parental feeding practices.

PMID- 29342592
TI  - Adaptive principles of weight regulation: Insufficient, but perhaps necessary,
      for understanding obesity.
AB  - We reflect on the major issues raised by a thoughtful and diverse set of
      commentaries on our target article. We draw attention to the need to
      differentiate between ultimate and proximate explanation; the insurance
      hypothesis (IH) needs to be understood as an ultimate-level argument, although we
      welcome the various suggestions made about proximate mechanisms. Much of this
      response is concerned with clarifying the interrelationships between
      adaptationist explanations like the IH, constraint explanations, and dysfunction
      explanations, in understanding obesity. We also re-examine the empirical evidence
      base, concurring that it is equivocal and only partially supportive. Several
      commentators offer additional supporting evidence, whereas others propose
      alternative explanations for the evidence we reviewed and suggest ways that our
      current knowledge could be strengthened. Finally, we take the opportunity to
      clarify some of the assumptions and predictions of our formal model.

PMID- 29342593
TI  - Parallel attentive processing and pre-attentive guidance.
AB  - This commentary focuses on two related, open questions in Hulleman & Olivers'
      (H&O's) proposal: (1) the nature of the parallel attentive process that
      determines target presence within, and thus presumably the size of, the
      functional visual field, and (2) how the pre-attentive guidance mechanism must be
      conceived to also account for search performance in tasks that afford no reliable
      target-based guidance.

PMID- 29342594
TI  - "Target-absent" decisions in cancer nodule detection are more efficient than
      "target-present" decisions!
AB  - Many parts of the medical image are never fixated when a radiologist searches for
      cancer nodules. Experts are able to use peripheral vision very efficiently. The
      size of the functional visual field appears to increase according to the level of
      expertise. However, searching a medical image diverges, in a puzzling way, from
      the typical search for a target feature in the laboratory.

PMID- 29342595
TI  - Contextual and social cues may dominate natural visual search.
AB  - A framework where only the size of the functional visual field of fixations can
      vary is hardly able to explain natural visual-search behavior. In real-world
      search tasks, context guides eye movements, and task-irrelevant social stimuli
      may capture the gaze.

PMID- 29342596
TI  - An appeal against the item's death sentence: Accounting for diagnostic data
      patterns with an item-based model of visual search.
AB  - We show that our item-based model, competitive guided search, accounts for the
      empirical patterns that Hulleman & Olivers (H&O) invoke against item-based
      models, and we highlight recently reported diagnostic data that challenge their
      approach. We advise against "forsaking the item" unless and until a full fixation
      based model is shown to be superior to extant item-based models.

PMID- 29342597
TI  - Chances and challenges for an active visual search perspective.
AB  - Using fixations as the fundamental unit of visual search is an appealing gear
      change in a paradigm that has long dominated attention research. To truly inform
      theories of search, however, additional challenges must be faced, including (1)
      an empirically motivated definition of fixation in the presence of fixational
      saccades and (2) the biases and limitations of transsaccadic perception and
      memory.

PMID- 29342598
TI  - Mathematical fixation: Search viewed through a cognitive lens.
AB  - We provide a mathematical category theory account of the size and location of the
      authors' Functional View Field (FVF). Category theory explains systematic
      cognitive ability via universal construction, that is, a necessary and sufficient
      condition for composition of cognitive processes. Similarly, FVF size and
      location is derived from a (universal) construction called a fibre (pullback)
      bundle.

PMID- 29342599
TI  - Those pernicious items.
AB  - Hulleman & Olivers (H&O) identify a number of problems with item-based thinking
      and its impact on our understanding of visual search. I detail ways in which item
      thought is worse than the authors suggest. I concur with the broad strokes of the
      theory they set out, and also clarify the relationship between their view and our
      recent theory of visual search.

PMID- 29342600
TI  - Where the item still rules supreme: Time-based selection, enumeration, pre
      attentive processing and the target template?
AB  - I propose that there remains a central role for the item (or its equivalent) in a
      wider range of search and search-related tasks/functions than might be conveyed
      by the article. I consider the functional relationship between the framework and
      some aspects of previous theories, and suggest some challenges that the new
      framework might encounter.

PMID- 29342601
TI  - "I am not dead yet!" - The Item responds to Hulleman & Olivers.
AB  - The item can only be dispensed within artificial tasks that, although useful in
      the lab, do not reflect the real world. There, the attended item is the goal of
      search. Hulleman & Olivers' (H&O's) model can ignore the item only by reducing
      search to the question of whether a patch of 0s (distractors) contains a 1
      (target).

PMID- 29342602
TI  - Task implementation and top-down control in continuous search.
AB  - Evidence from continuous search suggests that targets are detected by default,
      whereas distractors are processed in considerable depth. These observations shed
      light on task implementation and top-down control. Task implementation builds on
      forming dynamic distractor models, based on continuous integration of distractor
      related information. Top-down control builds on using these models for testing
      upcoming stimulus information.

PMID- 29342603
TI  - The "item" as a window into how prior knowledge guides visual search.
AB  - We challenge the central idea proposed in Hulleman & Olivers (H&O) by arguing
      that the "item" is still useful for understanding visual search and for
      developing new theoretical frameworks. The "item" is a flexible unit that
      represents not only an individual object, but also a bundle of objects that are
      grouped based on prior knowledge. Uncovering how the "item" is represented based
      on prior knowledge is essential for advancing theories of visual search.

PMID- 29342604
TI  - Eye movements are an important part of the story, but not the whole story.
AB  - Some previous accounts of visual search have emphasized covert attention at the
      expense of eye movements, and others have focused on eye movements while ignoring
      covert attention. Both selection mechanisms are likely to contribute to many
      searches, and a full account of search will probably need to explain how the two
      interact to find visual targets.

PMID- 29342605
TI  - Fixations are not all created equal: An objection to mindless visual search.
AB  - This call to revolution in theories of visual search does not go far enough.
      Treating fixations as uniform is an oversimplification that obscures the critical
      role of the mind. We remind readers that what happens during a fixation depends
      on mindset, as shown in studies of search strategy and of humans' ability to
      rapidly resume search following an interruption.

PMID- 29342606
TI  - Analysing real-world visual search tasks helps explain what the functional visual
      field is, and what its neural mechanisms are.
AB  - Rejecting information-processing-based theory permits the merging of a top-down
      analysis of visual search tasks with a bottom-up analysis of brain structure and
      function. This reveals the true nature of the functional visual field and its
      precise role in the conduct of visual search tasks. The merits of such analyses
      over the traditional methods of the authors are described.

PMID- 29342607
TI  - Item-based selection is in good shape in visual compound search: A view from
      electrophysiology.
AB  - We argue that although the framework put forward by Hulleman & Olivers (H&O) can
      successfully explain much of visual search behaviour, it appears limited to tasks
      without precise target identification demands. In particular, we contend that the
      unit of selection may be larger than a single item in standard detection tasks,
      whereas the unit may mandatorily be item-based in compound tasks.

PMID- 29342608
TI  - Set size slope still does not distinguish parallel from serial search.
AB  - Much of the evidence for theories in visual search (including Hulleman & Olivers'
      [H&O's]) comes from inferences made using changes in mean RT as a function of the
      number of items in a display. We have known for more than 40 years that these
      inferences are based on flawed reasoning and obscured by model mimicry. Here we
      describe a method that avoids these problems.

PMID- 29342609
TI  - The FVF framework and target prevalence effects.
AB  - The Functional Visual Field (FVF) offers explanatory power. To us, it relates to
      existing literature on the flexibility of attentional focus in visual search and
      reading (Eriksen & St. James 1986; McConkie & Rayner 1975). The target article
      promotes reflection on existing findings. Here we consider the FVF as a mechanism
      in the Prevalence Effect (PE) in visual search.

PMID- 29342610
TI  - Scanning movements during haptic search: similarity with fixations during visual
      search.
AB  - Finding relevant objects through vision, or visual search, is a crucial function
      that has received considerable attention in the literature. After decades of
      research, data suggest that visual fixations are more crucial to understanding
      how visual search works than are the attributes of stimuli. This idea receives
      further support from the field of haptic search.

PMID- 29342611
TI  - Feature integration, attention, and fixations during visual search.
AB  - We argue that mechanistic premises of "item-based" theories are not invalidated
      by the fixation-based approach. We use item-based theories to propose an account
      that does not advocate strict serial item processing and integrates fixations.
      The main focus of this account is feature integration within fixations. We also
      suggest that perceptual load determines the size of the fixations.

PMID- 29342612
TI  - The FVF might be influenced by object-based attention.
AB  - Hulleman & Olivers (H&O) argue that the primary unit in search should be
      fixations, and in doing so posit a Functional View Field (FVF). There is evidence
      from the object-based visual attention literature that the FVF may not process
      visual information uniformly. Here I sketch how object-based attention may
      influence processing within the FVF as well as the shape of the FVF.

PMID- 29342613
TI  - On the brink: The demise of the item in visual search moves closer.
AB  - We proposed to abandon the item as conceptual unit in visual search and adopt a
      fixation-based framework instead. We treat various themes raised by our
      commentators, including the nature of the Functional Visual Field and existing
      similar ideas, alongside the importance of items, covert attention, and top
      down/contextual influences. We reflect on the current state of, and future
      directions for, visual search.

PMID- 29342614
TI  - Searching for unity: Real-world versus item-based visual search in age-related
      eye disease.
AB  - When studying visual search, item-based approaches using synthetic targets and
      distractors limit the real-world applicability of results. Everyday visual search
      can be impaired in patients with common eye diseases like glaucoma and age
      related macular degeneration. We highlight some results in the literature that
      suggest assessment of real-word search tasks in these patients could be
      clinically useful.

PMID- 29342615
TI  - Gaze-contingent manipulation of the FVF demonstrates the importance of fixation
      duration for explaining search behavior.
AB  - Hulleman & Olivers' (H&O's) model introduces variation of the functional visual
      field (FVF) for explaining visual search behavior. Our research shows how the FVF
      can be studied using gaze-contingent displays and how FVF variation can be
      implemented in models of gaze control. Contrary to H&O, we believe that fixation
      duration is an important factor when modeling visual search behavior.

PMID- 29342616
TI  - Oh, the number of things you will process (in parallel)!
AB  - We highlight the importance of considering the variance produced during the
      parallel processing stage in vision and present a case for why it is useful to
      consider the "item" as a meaningful unit of study when investigating early visual
      processing in visual search tasks.

PMID- 29342617
TI  - What fixations reveal about oculomotor scanning behavior in visual search.
AB  - Hulleman & Olivers' (H&O's) conceptual framework does not consider variation of
      fixation duration and its interaction with the size of the functional viewing
      field (FVF). Here we provide empirical evidence of a dynamic interaction between
      the two parameters, suggesting that fixations, as the central unit in H&O's
      framework, should be studied on both the spatial and temporal dimensions.

PMID- 29342618
TI  - Why the item will remain the unit of attentional selection in visual search.
AB  - Hulleman & Olivers (H&O) reject item-based serial models of visual search, and
      they suggest that items are processed equally and globally during each fixation
      period. However, neuroscientific studies have shown that attentional biases can
      emerge in parallel but in a spatially selective item-based fashion. Even within a
      parallel architecture for visual search, the item remains the critical unit of
      selection.

PMID- 29342619
TI  - Until the demise of the functional field of view.
AB  - Hulleman & Olivers (H&O) make a much-needed stride forward for a better
      understanding of visual search behavior by rejecting theories based on discrete
      stimulus items. I propose that the framework could be further enhanced by clearly
      delineating distinct mechanisms for attention guidance, selection, and
      enhancement during visual search, instead of conflating them into a single
      functional field of view.

PMID- 29342620
TI  - How functional are functional viewing fields?
AB  - Hulleman & Olivers' (H&O's) proposal is a refreshing addition to the visual
      search literature. Although we like their proposal that fixations, not individual
      items should be considered a fundamental unit in visual search, we point out some
      unresolved problems that their account will have to solve. Additionally, we
      consider predictions that can be made from the account, in particular in relation
      to priming of visual search, finding that the account generates interesting
      testable predictions.

PMID- 29342621
TI  - Don't admit defeat: A new dawn for the item in visual search.
AB  - Even though we lack a precise definition of "item," it is clear that people do
      parse their visual environment into objects (the real-world equivalent of items).
      We will review evidence that items are essential in visual search, and argue that
      computer vision - especially deep learning - may offer a solution for the lack of
      a solid definition of "item."

PMID- 29342622
TI  - Cognitive architecture enables comprehensive predictive models of visual search.
AB  - With a simple demonstration model, Hulleman & Olivers (H&O) effectively argue
      that theories of visual search need an overhaul. We point to related literature
      in which visual search is modeled in even more detail through the use of
      computational cognitive architectures that incorporate fundamental perceptual,
      cognitive, and motor mechanisms; the result of such work thus far bolsters their
      arguments considerably.

PMID- 29342623
TI  - Looking further! The importance of embedding visual search in action.
AB  - A unified account of visual search in complex everyday environments requires
      additional deliberations on the functional grounding of Hulleman & Olivers'
      (H&O's) functional viewing field (FVF) model. Their model can accommodate
      exploitation of information that is distributed across the immediate environment.
      Yet the differences in search between genuinely interacting in the environment
      and merely watching it should challenge researchers to look further.

PMID- 29342625
TI  - Evidence for a number sense.
AB  - Numerosity is inherently confounded by related stimulus attributes such as
      density and area, and many studies have reported interactions of various
      strengths between area, density, and numerosity. However, direct measurements of
      sensitivity within the area-density-numerosity space show that numerosity emerges
      as the most spontaneous and sensitive dimension, strongly supporting the
      existence of a dedicated number sense.

PMID- 29342624
TI  - Infants discriminate number: Evidence against the prerequisite of visual object
      individuation and the primacy of continuous magnitude.
AB  - Leibovich et al. hypothesize that the absence of visual object individuation
      limits infants' numerical skills and necessitates a reliance on continuous
      magnitudes. We argue that parallels between infants' numerical discrimination in
      the visual and auditory modalities, their abilities to match numerosities across
      modalities, and their greater ability to discriminate changes in number compared
      with continuous magnitudes contradict the authors' assumptions.

PMID- 29342626
TI  - Why try saving the ANS? An alternative proposal.
AB  - Leibovich et al. propose that continuous magnitudes and a number sense are used
      holistically to judge numerosity. We point out that their proposal is incomplete
      and implausible: incomplete, as it does not explain how continuous magnitudes are
      calculated; implausible, as it cannot explain performance in estimation tasks. We
      propose that we do not possess a number sense. Instead, we assume that numerosity
      judgments are accomplished by weighing the different continuous magnitudes
      constituting numerosity.

PMID- 29342627
TI  - Magnitude, numerosity, and development of number: Implications for mathematics
      disabilities.
AB  - Leibovich et al. challenge the prevailing view that non-symbolic number sense
      (e.g., sensing number the same way one might sense color) is innate, that
      detection of numerosity is distinct from detection of continuous magnitude. In
      the present commentary, the authors' viewpoint is discussed in light of the
      integrative theory of numerical development along with implications for
      understanding mathematics disabilities.

PMID- 29342628
TI  - Commentary on Leibovich et al.: What next?
AB  - The conclusions reached by Leibovich et al. urge the field to regroup and
      consider new ways of conceptualizing quantitative development. We suggest three
      potential directions for new research that follow from the authors' extensive
      review, as well as building on the common ground we can take from decades of
      research in this area.

PMID- 29342629
TI  - How not to develop a sense of number.
AB  - The authors rightly point to the theoretical importance of interactions of space
      and number through the life span, yet propose a theory with several weaknesses.
      In addition to proclaiming itself unfalsifiable, its stage-like format and
      emphasis on the role of selective attention are at odds with what is known about
      the development of spatial-numerical associations in infancy.

PMID- 29342630
TI  - A "sense of magnitude" requires a new alternative for learning numerical symbols.
AB  - Leibovich et al. proposed that the processing of numerosities is based primarily
      on a "sense of magnitude." The consequences of this proposal for how numerical
      symbols acquire their meaning are, however, neglected. We argue that symbols
      cannot be learned by associating them with a system that is not yet able to
      derive discrete numbers accurately because of immature cognitive control.

PMID- 29342631
TI  - Right idea, wrong magnitude system.
AB  - Leibovich et al. claim that number representations are non-existent early in life
      and that the associations between number and continuous magnitudes reside in
      stimulus confounds. We challenge both claims - positing, instead, that number is
      represented independently of continuous magnitudes already in infancy, but is
      nonetheless more deeply connected to other magnitudes through adulthood than
      acknowledged by the "sense of magnitude" theory.

PMID- 29342632
TI  - The contributions of non-numeric dimensions to number encoding, representations,
      and decision-making factors.
AB  - Leibovich et al. suggest that congruency effects in number perception (biases
      towards smaller, denser, etc., dots) are evidence for the number's dependence on
      these dimensions. I argue that they fail to differentiate between effects at
      three distinct levels of number perception - encoding, representations, and
      decision making - and that differentiating between these allows the number to be
      independent from, but correlated with, non-numeric dimensions.

PMID- 29342633
TI  - Numerical magnitude evaluation as a foundation for decision making.
AB  - The evaluation of magnitudes serves as a foundation not only for numerical and
      mathematical cognition, but also for decision making. Recent theoretical
      developments and empirical studies have linked numerical magnitude evaluation to
      a wide variety of core phenomena in decision making and challenge the idea that
      preferences are driven by an innate, universal, and stable sense of number or
      value.

PMID- 29342634
TI  - Direct and rapid encoding of numerosity in the visual stream.
AB  - The target article dismisses all prior work purporting to demonstrate that number
      is a conceptual primitive. Here, we take issue with their misrepresentation of
      our recent line of work on numerosity perception, which demonstrates rapid and
      direct encoding of numerosity and undermines the thesis of the target article
      that "continuous magnitudes are more automatic and basic than numerosities"
      (sect. 1, para. 2).

PMID- 29342635
TI  - Numerical intuitions in infancy: Give credit where credit is due.
AB  - Leibovich et al. overlook numerous human infant studies pointing to an early
      emerging number sense. These studies have carefully manipulated continuous
      magnitudes in the context of a numerical task revealing that infants can
      discriminate number when extent is controlled, that infants fail to track extent
      cues with precision, and that infants find changes in extent less salient than
      numerical changes.

PMID- 29342636
TI  - Selecting the model that best fits the data.
AB  - Leibovich et al. argue that that none of the experiments they review really
      establishes that human adults, infants, or nonhuman animals are sensitive to
      numerosity independent of a range of continuous quantities. We do not dispute
      their claim that the empirical record is inconclusive but argue that model-based
      data analysis does offer a way to make progress.

PMID- 29342637
TI  - Multitudes are adaptable magnitudes in the estimation of number.
AB  - Visual number comparison does not require participants to choose a unit, whereas
      units are fundamental to the definition of number. Studies using magnitude
      estimation rather than comparison show that number perception is compressed
      dramatically past about 20 units. Even estimates of 5-20 items are increasingly
      susceptible to effects of visual adaptation, suggesting a rather narrow range in
      which subitizing-like categorization processes blend into greater reliance on
      adaptable magnitude information.

PMID- 29342638
TI  - The contribution of fish studies to the "number sense" debate.
AB  - Leibovich et al. propose that number sense is not innate but gradually emergent
      during ontogeny following experience. We argue that this hypothesis cannot be
      reasonably tested in humans, in which the contribution of neural maturation and
      experience cannot be experimentally manipulated. Studies on animals, especially
      fish, can more effectively provide critical insights into the innate nature of
      numerical abilities.

PMID- 29342639
TI  - Number faculty is alive and kicking: On number discriminations and number
      neurons.
AB  - Leibovich et al. advocate for a single "sense of magnitude" to which a dedicated
      faculty for number could allegedly be reduced. This conclusion is unjustified as
      the authors adopt an unnecessarily narrow definition of "number sense," neglect
      studies that demonstrate non-symbolic numerosity representation, and furthermore
      ignore abstract number representations in the brain.

PMID- 29342640
TI  - Innateness of magnitude perception? Skill can be acquired and mastered at all
      ages.
AB  - We agree with Leibovich et al.'s argument that the number sense theory should be
      re-evaluated. However, we argue that highly efficient skills (i.e., fluent and
      highly accurate, "automatic," performance) can be acquired and mastered at all
      ages. Hence, evidence for primacy or fluency in perceiving continuous magnitudes
      is insufficient for supporting strong conclusions about the innateness of this
      aptitude.

PMID- 29342641
TI  - Magnitude rather than number: More evidence needed.
AB  - Leibovich et al. do not present enough empirical support to overturn decades of
      work supporting a number sense nor to convince the reader that a magnitude sense
      provides a better explanation of the literature. Here we highlight what we feel
      are the main points of weakness and the types of evidence that could be provided
      to be more convincing.

PMID- 29342642
TI  - Is the ANS linked to mathematics performance?
AB  - Leibovich et al. argue persuasively that researchers should not assume that
      approximate number system (ANS) tasks harness an innate sense of number. However,
      some studies have reported a causal link between ANS tasks and mathematics
      performance, implicating the ANS in the development of numerical skills. Here we
      report a p-curve analysis, which indicates that these experimental studies do not
      contain evidential value.

PMID- 29342643
TI  - Infants, animals, and the origins of number.
AB  - Where do human numerical abilities come from? Leibovich et al. argue against
      nativist views of numerical development noting limitations in newborns' vision
      and limitations regarding newborns' ability to individuate objects. I argue that
      these considerations do not undermine competing nativist views and that Leibovich
      et al.'s model itself presupposes that infant learners have numerical
      representations.

PMID- 29342644
TI  - What is the precise role of cognitive control in the development of a sense of
      number?
AB  - The theory put forward by Leibovich et al. of how children acquire a sense of
      number does not specify the mechanisms through which cognitive control plays a
      role in this process. We argue that visual attention and number word knowledge
      influence each other over development and contribute to the development of the
      concept of number.

PMID- 29342645
TI  - What is a number? The interplay between number and continuous magnitudes.
AB  - Leibovich et al. argue that it is impossible to control for all continuous
      magnitudes in a numerical task. We contend that continuous magnitudes (i.e.,
      perimeter, area, density) can be simultaneously controlled. Furthermore, we argue
      that shedding light on the interplay between number and continuous magnitudes -
      rather than considering them independently - will provide a much more fruitful
      approach to understanding mathematical abilities.

PMID- 29342646
TI  - The evolvement of discrete representations from continuous stimulus properties: A
      possible overarching principle of cognition.
AB  - Leibovich et al. propose that non-symbolic numerosity abilities develop from the
      processing of more basic, continuous magnitudes such as size, area, and density.
      Here I review similar arguments arising in the visual perception field and
      further propose that the evolvement of discrete representations from continuous
      stimulus properties may be a fundamental characteristic of cognitive development.

PMID- 29342647
TI  - Controlling for continuous variables is not futile: What we can learn about
      number representation despite imperfect control.
AB  - Leibovich et al. argue that because it is impossible to isolate numerosity in a
      stimulus set, attempts to show that number is processed independently of
      continuous magnitudes are necessarily in vain. I propose that through clever
      design and manipulation of confounding variables, we can gain deep insight into
      number representation and its relationship to the representation of other
      magnitudes.

PMID- 29342648
TI  - Toward an integrative approach to numerical cognition.
AB  - In response to the commentaries, we have refined our suggested model and
      discussed ways in which the model could be further expanded. In this context, we
      have elaborated on the role of specific continuous magnitudes. We have also found
      it important to devote a section to evidence considered the "smoking gun" of the
      approximate number system theory, including cross-modal studies, animal studies,
      and so forth. Lastly, we suggested some ways in which the scientific community
      can promote more transparent and collaborative research by using an open science
      approach, sharing both raw data and stimuli. We thank the contributors for their
      enlightening comments and look forward to future developments in the field.

PMID- 29342649
TI  - Approximate number sense theory or approximate theory of magnitude?
AB  - Leibovich et al. argue that the evidence in favor of a perceptual mechanism
      devoted to the extraction of numerosity from visual collections is unsatisfactory
      and propose to replace it with an unspecific mechanism capturing approximate
      magnitudes from continuous dimensions. We argue that their representation of the
      evidence is incomplete and that their theoretical proposal is too vague to be
      useful.

PMID- 29342650
TI  - Computational foundations of the visual number sense.
AB  - We provide an emergentist perspective on the computational mechanism underlying
      numerosity perception, its development, and the role of inhibition, based on our
      deep neural network model. We argue that the influence of continuous visual
      properties does not challenge the notion of number sense, but reveals limit
      conditions for the computation that yields invariance in numerosity perception.
      Alternative accounts should be formalized in a computational model.

PMID- 29342651
TI  - The number sense is neither last resort nor of primary import.
AB  - Leibovich et al. argue that evidence for an innate sense of number in children
      and animals may instead reflect the processing of continuous magnitude
      properties. However, some comparative research highlights responding on the basis
      of numerosity when non-numerical confounds are controlled. Future comparative
      tests might evaluate how early experience with continuous magnitudes affects the
      development of a sense of number.

PMID- 29342652
TI  - Perceiving numerosity from birth.
AB  - Leibovich et al. opened up an important discussion on the nature and origins of
      numerosity perception. The authors rightly point out that non-numerical features
      of stimuli influence this ability. Despite these biases, there is evidence that
      from birth, humans perceive and represent numerosities, and not just non
      numerical quantitative features such as item size, density, and convex hull.

PMID- 29342653
TI  - From continuous magnitudes to symbolic numbers: The centrality of ratio.
AB  - Leibovich et al.'s theory neither accounts for the deep connections between whole
      numbers and other classes of number nor provides a potential mechanism for
      mapping continuous magnitudes to symbolic numbers. We argue that focusing on non
      symbolic ratio processing abilities can furnish a more expansive account of
      numerical cognition that remedies these shortcomings.

PMID- 29342654
TI  - Negative results are needed to show the specific value of a cultural explanation
      for g.
AB  - Burkart et al. suggest that social learning can explain the cognitive positive
      manifold for social animals, including humans. We caution that simpler
      explanations of positive trait intercorrelations exist, such as genetic load. To
      test the suggested explanation's specificity, we also need to examine non-social
      species and traits, such as health, that are distal to cognitive abilities.

PMID- 29342655
TI  - Domains of generality.
AB  - We argue that general intelligence, as presented in the target article, generates
      multiple distinct and non-equivalent characterisations. Clarifying this central
      concept is necessary for assessing Burkart et al.'s proposal that the cultural
      intelligence hypothesis is the best explanation for the evolution of general
      intelligence. We assess this claim by considering two characterisations of
      general intelligence presented in the article.

PMID- 29342656
TI  - Theory of mind: A foundational component of human general intelligence.
AB  - To understand the evolution of general intelligence, Burkart et al. endorse a
      "cultural intelligence approach," which emphasizes the critical importance of
      social interaction. We argue that theory of mind provides an essential foundation
      and shared perspective for the efficient ontogenetic transmission of crucial
      knowledge and skills during human development and, together with language, can
      account for superior human general intelligence.

PMID- 29342657
TI  - Coexistence of general intelligence and specialized modules.
AB  - Here, we specifically discuss why and to what extent we agree with Burkart et al.
      about the coexistence of general intelligence and modular cognitive adaptations,
      and why we believe that the distinction between primary and secondary modules
      they propose is indeed essential.

PMID- 29342658
TI  - G but not g: In search of the evolutionary continuity of intelligence.
AB  - Conceptualizing intelligence in its biological context, as the expression of
      manifold adaptations, compels a rethinking of measuring this characteristic in
      humans, relying also on animal studies of analogous skills. Mental manipulation,
      as an extension of object manipulation, provides a continuous, biologically based
      concept for studying G as it pertains to individual differences in humans and
      other species.

PMID- 29342659
TI  - Taking a multiple intelligences (MI) perspective.
AB  - The theory of multiple intelligences (MI) seeks to describe and encompass the
      range of human cognitive capacities. In challenging the concept of general
      intelligence, we can apply an MI perspective that may provide a more useful
      approach to cognitive differences within and across species.

PMID- 29342660
TI  - The evolution of general intelligence in all animals and machines.
AB  - We strongly agree that general intelligence occurs in many animals but find the
      cultural intelligence hypothesis of limited usefulness. Any viable hypothesis
      explaining the evolution of general intelligence should be able to account for it
      in all species where it is known to occur, and should also predict the conditions
      under which we can develop machines with general intelligence as well.

PMID- 29342661
TI  - The false dichotomy of domain-specific versus domain-general cognition.
AB  - The qualitative division between domain-general and domain-specific cognition is
      unsubstantiated. The distinction is instead better viewed as opposites on a
      gradual scale, which has more explanatory power and fits current empirical
      evidence better. We also argue that causal cognition may be more general than
      social learning, which it often involves.

PMID- 29342662
TI  - Contemporary evolutionary psychology and the evolution of intelligence.
AB  - Burkart et al.'s impressive synthesis will serve as a valuable resource for
      intelligence research. Despite its strengths, the target article falls short of
      offering compelling explanations for the evolution of intelligence. Here, we
      outline its shortcomings, illustrate how these can lead to misguided conclusions
      about the evolution of intelligence, and suggest ways to address the article's
      key questions.

PMID- 29342663
TI  - Understanding the relationship between general intelligence and socio-cognitive
      abilities in humans.
AB  - Burkart et al. consider that the relationship between general intelligence and
      socio-cognitive abilities is poorly understood in animals and humans. We examine
      this conclusion in the perspective of an already substantial evidence base on the
      relationship among general intelligence, theory of mind, and emotional
      intelligence. We propose a link between general intelligence and socio-cognitive
      abilities within humans.

PMID- 29342664
TI  - Of mice and men, nature and nurture, and a few red herrings.
AB  - Burkart et al.'s proposal is based on three false premises: (1) theories of the
      mind are either domain-specific/modular (DSM) or domain-general (DG); (2) DSM
      systems are considered inflexible, built by nature; and (3) animal minds are
      deemed as purely DSM. Clearing up these conceptual confusions is a necessary
      first step in understanding how general intelligence evolved.

PMID- 29342665
TI  - Where is the evidence for general intelligence in nonhuman animals?
AB  - This commentary contrasts evolutionary plausibility with empirical evidence and
      cognitive continuity with radiation and convergent evolution. So far, neither
      within-species nor between-species comparisons on the basis of rigorous
      experimental and species-appropriate tests substantiate the claims made in the
      target article. Caution is advisable on meta-analytical comparisons that
      primarily rely on publication frequencies and overgeneralizations (from murids
      and primates to other nonhuman animals).

PMID- 29342666
TI  - The evolution of fluid intelligence meets formative g.
AB  - The argument by Burkart et al. in the target article relates to fluid (not
      general) intelligence: a domain-general ability involved in complex, novel
      problem solving, and strongly related to working memory and executive functions.
      A formative framework, under which the general factor of intelligence is the
      common consequence, not the common cause of the covariance among tests is more in
      line with an evolutionary approach.

PMID- 29342667
TI  - Hierarchy, multidomain modules, and the evolution of intelligence.
AB  - In this commentary, we support a complex, mosaic, and multimodal approach to the
      evolution of intelligence. Using the arcuate fasciculus as an example of
      discontinuity in the evolution of neurobiological architectures, we argue that
      the strict dichotomy of modules versus G, adopted by Burkart et al. in the target
      article, is insufficient to interpret the available statistical and experimental
      evidence.

PMID- 29342668
TI  - Habit formation generates secondary modules that emulate the efficiency of
      evolved behavior.
AB  - We discuss the evolutionary implications of connections drawn between the
      authors' learned "secondary modules" and the habit-formation system that appears
      to be ubiquitous among vertebrates. Prior to any subsequent coevolution with
      social learning, we suggest that aspects of general intelligence likely arose in
      tandem with mechanisms of adaptive motor control that rely on basal ganglia
      circuitry.

PMID- 29342669
TI  - "Birdbrains" should not be ignored in studying the evolution of g.
AB  - The authors evaluate evidence for general intelligence (g) in nonhumans but lean
      heavily toward mammalian data. They mention, but do not discuss in detail,
      evidence for g in nonmammalian species, for which substantive material exists. I
      refer to a number of avian studies, particularly in corvids and parrots, which
      would add breadth to the material presented in the target article.

PMID- 29342670
TI  - Evolution, brain size, and variations in intelligence.
AB  - Across taxonomic subfamilies, variations in intelligence (G) are sometimes
      related to brain size. However, within species, brain size plays a smaller role
      in explaining variations in general intelligence (g), and the cause-and-effect
      relationship may be opposite to what appears intuitive. Instead, individual
      differences in intelligence may reflect variations in domain-general processes
      that are only superficially related to brain size.

PMID- 29342671
TI  - The evolution of analytic thought?
AB  - We argue that the truly unique aspect of human intelligence is not the variety of
      cognitive skills that are ontogenetically constructed, but rather the capacity to
      decide when to develop and apply said skills. Even if there is good evidence for
      g in nonhuman animals, we are left with major questions about how the disposition
      to think analytically can evolve.

PMID- 29342672
TI  - General intelligence is an emerging property, not an evolutionary puzzle.
AB  - Burkart et al. contend that general intelligence poses a major evolutionary
      puzzle. This assertion presupposes a reification of general intelligence - that
      is, assuming that it is one "thing" that must have been selected as such.
      However, viewing general intelligence as an emerging property of multiple
      cognitive abilities (each with their own selective advantage) requires no
      additional evolutionary explanation.

PMID- 29342673
TI  - General intelligence does not help us understand cognitive evolution.
AB  - Burkart et al. conflate the domain-specificity of cognitive processes with the
      statistical pattern of variance in behavioural measures that partly reflect those
      processes. General intelligence is a statistical abstraction, not a cognitive
      trait, and we argue that the former does not warrant inferences about the nature
      or evolution of the latter.

PMID- 29342674
TI  - When does cultural transmission favour or instead substitute for general
      intelligence?
AB  - The cultural intelligence hypothesis is an exciting new development. The
      hypothesis that it encourages general intelligence is intriguing, but it presents
      a paradox insofar as social learning is often suggested to instead reduce
      reliance on individual cognition and exploration. There is thus a need to specify
      more clearly the contexts in which cultural transmission may select for general
      intelligence.

PMID- 29342675
TI  - An all-positive correlation matrix is not evidence of domain-general
      intelligence.
AB  - We welcome the cross-disciplinary approach taken by Burkart et al. to probe the
      evolution of intelligence. We note several concerns: the uses of g and G, rank
      ordering species on cognitive ability, and the meaning of general intelligence.
      This subject demands insights from several fields, and we look forward to cross
      disciplinary collaborations.

PMID- 29342676
TI  - Disentangling learning from knowing: Does associative learning ability underlie
      performances on cognitive test batteries?
AB  - Are the mechanisms underlying variations in the performance of animals on
      cognitive test batteries analogous to those of humans? Differences might result
      from procedural inconsistencies in test battery design, but also from differences
      in how animals and humans solve cognitive problems. We suggest differentiating
      associative-based (learning) from rule-based (knowing) tasks to further our
      understanding of cognitive evolution across species.

PMID- 29342677
TI  - General intelligence is a source of individual differences between species:
      Solving an anomaly.
AB  - Burkart et al. present a paradox - general factors of intelligence exist among
      individual differences (g) in performance in several species, and also at the
      aggregate level (G); however, there is ambiguous evidence for the existence of g
      when analyzing data using a mixed approach, that is, when comparing individuals
      of different species using the same cognitive ability battery. Here, we present
      an empirical solution to this paradox.

PMID- 29342678
TI  - Genomic data can illuminate the architecture and evolution of cognitive
      abilities.
AB  - Does general intelligence exist across species, and has it been a target of
      natural selection? These questions can be addressed with genomic data, which can
      rule out artifacts by demonstrating that distinct cognitive abilities are
      genetically correlated and thus share a biological substrate. This work has begun
      with data from humans and can be extended to other species; it should focus not
      only on general intelligence but also specific capacities like language and
      spatial ability.

PMID- 29342679
TI  - Future directions for studying the evolution of general intelligence.
AB  - The goal of our target article was to lay out current evidence relevant to the
      question of whether general intelligence can be found in nonhuman animals in
      order to better understand its evolution in humans. The topic is a controversial
      one, as evident from the broad range of partly incompatible comments it has
      elicited. The main goal of our response is to translate these issues into
      testable empirical predictions, which together can provide the basis for a broad
      research agenda.

PMID- 29342680
TI  - G and g: Two markers of a general cognitive ability, or none?
AB  - The search for general processes that underlie intelligence in nonhumans has
      followed two strategies: one that concerns observing differences between nonhuman
      species (G), the second that concerns observing individual differences within a
      nonhuman species (g). This commentary takes issue with both attempts to mark a
      general factor: Differential responding to contextual variables compromises the
      search for G, and the lack of predictive validity compromises g.

PMID- 29342681
TI  - A pointer's hypothesis of general intelligence evolved from domain-specific
      demands.
AB  - A higher-order function may evolve phylogenetically if it is demanded by multiple
      domain-specific modules. Task-specificity to solve a unique adaptive problem
      (e.g., foraging or mating) should be distinguished from function-specificity to
      deal with a common computational demand (e.g., numeracy, verbal communication)
      required by many tasks. A localized brain function is likely a result of such
      common computational demand.

PMID- 29342682
TI  - It's time to move beyond the "Great Chain of Being".
AB  - The target article provides an anthropocentric model of understanding
      intelligence in nonhuman animals. Such an idea dates back to Plato and, more
      recently, Lovejoy: On Earth, humans are at the top and other animals at
      successively lower levels. We then evaluate these other animals by our
      anthropocentric folk theories of their intelligence rather than by their own
      adaptive requirements.

PMID- 29342683
TI  - Theories or fragments?
AB  - Lake et al. argue persuasively that modelling human-like intelligence requires
      flexible, compositional representations in order to embody world knowledge. But
      human knowledge is too sparse and self-contradictory to be embedded in "intuitive
      theories." We argue, instead, that knowledge is grounded in exemplar-based
      learning and generalization, combined with high flexible generalization, a
      viewpoint compatible both with non-parametric Bayesian modelling and with sub
      symbolic methods such as neural networks.

PMID- 29342684
TI  - The architecture challenge: Future artificial-intelligence systems will require
      sophisticated architectures, and knowledge of the brain might guide their
      construction.
AB  - In this commentary, we highlight a crucial challenge posed by the proposal of
      Lake et al. to introduce key elements of human cognition into deep neural
      networks and future artificial-intelligence systems: the need to design effective
      sophisticated architectures. We propose that looking at the brain is an important
      means of facing this great challenge.

PMID- 29342685
TI  - Building machines that learn and think for themselves.
AB  - We agree with Lake and colleagues on their list of "key ingredients" for building
      human-like intelligence, including the idea that model-based reasoning is
      essential. However, we favor an approach that centers on one additional
      ingredient: autonomy. In particular, we aim toward agents that can both build and
      exploit their own internal models, with minimal human hand engineering. We
      believe an approach centered on autonomous learning has the greatest chance of
      success as we scale toward real-world complexity, tackling domains for which
      ready-made formal models are not available. Here, we survey several important
      examples of the progress that has been made toward building autonomous agents
      with human-like abilities, and highlight some outstanding challenges.

PMID- 29342686
TI  - Back to the future: The return of cognitive functionalism.
AB  - The claims that learning systems must build causal models and provide
      explanations of their inferences are not new, and advocate a cognitive
      functionalism for artificial intelligence. This view conflates the relationships
      between implicit and explicit knowledge representation. We present recent
      evidence that neural networks do engage in model building, which is implicit, and
      cannot be dissociated from the learning process.

PMID- 29342687
TI  - Deep-learning networks and the functional architecture of executive control.
AB  - Lake et al. underrate both the promise and the limitations of contemporary deep
      learning techniques. The promise lies in combining those techniques with broad
      multisensory training as experienced by infants and children. The limitations lie
      in the need for such systems to possess functional subsystems that generate,
      monitor, and switch goals and strategies in the absence of human intervention.

PMID- 29342688
TI  - Children begin with the same start-up software, but their software updates are
      cultural.
AB  - We propose that early in ontogeny, children's core cognitive abilities are shaped
      by culturally dependent "software updates." The role of sociocultural inputs in
      the development of children's learning is largely missing from Lake et al.'s
      discussion of the development of human-like artificial intelligence, but its
      inclusion would help move research even closer to machines that can learn and
      think like humans.

PMID- 29342689
TI  - Causal generative models are just a start.
AB  - Human reasoning is richer than Lake et al. acknowledge, and the emphasis on
      theories of how images and scenes are synthesized is misleading. For example, the
      world knowledge used in vision presumably involves a combination of geometric,
      physical, and other knowledge, rather than just a causal theory of how the image
      was produced. In physical reasoning, a model can be a set of constraints rather
      than a physics engine. In intuitive psychology, many inferences proceed without
      detailed causal generative models. How humans reliably perform such inferences,
      often in the face of radically incomplete information, remains a mystery.

PMID- 29342690
TI  - What can the brain teach us about building artificial intelligence?
AB  - Lake et al. offer a timely critique on the recent accomplishments in artificial
      intelligence from the vantage point of human intelligence and provide insightful
      suggestions about research directions for building more human-like intelligence.
      Because we agree with most of the points they raised, here we offer a few points
      that are complementary.

PMID- 29342691
TI  - Thinking like animals or thinking like colleagues?
AB  - We comment on ways in which Lake et al. advance our understanding of the
      machinery of intelligence and offer suggestions. The first set concerns animal
      level versus human-level intelligence. The second concerns the urgent need to
      address ethical issues when evaluating the state of artificial intelligence.

PMID- 29342692
TI  - Evidence from machines that learn and think like people.
AB  - We agree with Lake et al.'s trenchant analysis of deep learning systems,
      including that they are highly brittle and that they need vastly more examples
      than do people. We also agree that human cognition relies heavily on structured
      relational representations. However, we differ in our analysis of human cognitive
      processing. We argue that (1) analogical comparison processes are central to
      human cognition; and (2) intuitive physical knowledge is captured by qualitative
      representations, rather than quantitative simulations.

PMID- 29342693
TI  - Understand the cogs to understand cognition.
AB  - Lake et al. suggest that current AI systems lack the inductive biases that enable
      human learning. However, Lake et al.'s proposed biases may not directly map onto
      mechanisms in the developing brain. A convergence of fields may soon create a
      correspondence between biological neural circuits and optimization in structured
      architectures, allowing us to systematically dissect how brains learn.

PMID- 29342694
TI  - Crossmodal lifelong learning in hybrid neural embodied architectures.
AB  - Lake et al. point out that grounding learning in general principles of embodied
      perception and social cognition is the next step in advancing artificial
      intelligent machines. We suggest it is necessary to go further and consider
      lifelong learning, which includes developmental learning, focused on embodiment
      as applied in developmental robotics and neurorobotics, and crossmodal learning
      that facilitates integrating multiple senses.

PMID- 29342695
TI  - Social-motor experience and perception-action learning bring efficiency to
      machines.
AB  - Lake et al. proposed a way to build machines that learn as fast as people do.
      This can be possible only if machines follow the human processes: the perception
      action loop. People perceive and act to understand new objects or to promote
      specific behavior to their partners. In return, the object/person provides
      information that induces another reaction, and so on.

PMID- 29342696
TI  - Autonomous development and learning in artificial intelligence and robotics:
      Scaling up deep learning to human-like learning.
AB  - Autonomous lifelong development and learning are fundamental capabilities of
      humans, differentiating them from current deep learning systems. However, other
      branches of artificial intelligence have designed crucial ingredients towards
      autonomous learning: curiosity and intrinsic motivation, social learning and
      natural interaction with peers, and embodiment. These mechanisms guide
      exploration and autonomous choice of goals, and integrating them with deep
      learning opens stimulating perspectives.

PMID- 29342697
TI  - The fork in the road.
AB  - Machines that learn and think like people should simulate how people really think
      in their everyday lives. The field of artificial intelligence originally traveled
      down two roads, one of which emphasized abstract, idealized, rational thinking
      and the other, which emphasized the emotionally charged and motivationally
      complex situations in which people often find themselves. The roads should have
      converged but never did. That's too bad.

PMID- 29342698
TI  - Avoiding frostbite: It helps to learn from others.
AB  - Machines that learn and think like people must be able to learn from others.
      Social learning speeds up the learning process and - in combination with language
      - is a gateway to abstract and unobservable information. Social learning also
      facilitates the accumulation of knowledge across generations, helping people and
      artificial intelligences learn things that no individual could learn in a
      lifetime.

PMID- 29342699
TI  - Digging deeper on "deep" learning: A computational ecology approach.
AB  - We propose an alternative approach to "deep" learning that is based on
      computational ecologies of structurally diverse artificial neural networks, and
      on dynamic associative memory responses to stimuli. Rather than focusing on
      massive computation of many different examples of a single situation, we opt for
      model-based learning and adaptive flexibility. Cross-fertilization of learning
      processes across multiple domains is the fundamental feature of human
      intelligence that must inform "new" artificial intelligence.

PMID- 29342700
TI  - Building brains that communicate like machines.
AB  - Reverse engineering human cognitive processes may improve artificial
      intelligence, but this approach implies we have little to learn regarding brains
      from human-engineered systems. On the contrary, engineered technologies of
      dynamic network communication have many features that highlight analogous, poorly
      understood, or ignored aspects of brain and cognitive function, and mechanisms
      fundamental to these technologies can be usefully investigated in brains.

PMID- 29342701
TI  - Building on prior knowledge without building it in.
AB  - Lake et al. propose that people rely on "start-up software," "causal models," and
      "intuitive theories" built using compositional representations to learn new tasks
      more efficiently than some deep neural network models. We highlight the many
      drawbacks of a commitment to compositional representations and describe our
      continuing effort to explore how the ability to build on prior knowledge and to
      learn new tasks efficiently could arise through learning in deep neural networks.

PMID- 29342702
TI  - Will human-like machines make human-like mistakes?
AB  - Although we agree with Lake et al.'s central argument, there are numerous flaws
      in the way people use causal models. Our models are often incorrect, resistant to
      correction, and applied inappropriately to new situations. These deficiencies are
      pervasive and have real-world consequences. Developers of machines with similar
      capacities should proceed with caution.

PMID- 29342703
TI  - The humanness of artificial non-normative personalities.
AB  - Technoscientific ambitions for perfecting human-like machines, by advancing state
      of-the-art neuromorphic architectures and cognitive computing, may end in ironic
      regret without pondering the humanness of fallible artificial non-normative
      personalities. Self-organizing artificial personalities individualize machine
      performance and identity through fuzzy conscientiousness, emotionality,
      extraversion/introversion, and other traits, rendering insights into technology
      assisted human evolution, robot ethology/pedagogy, and best practices against
      unwanted autonomous machine behavior.

PMID- 29342704
TI  - The importance of motivation and emotion for explaining human cognition.
AB  - Lake et al. discuss building blocks of human intelligence that are quite
      different from those of artificial intelligence. We argue that a theory of human
      intelligence has to incorporate human motivations and emotions. The interaction
      of motivation, emotion, and cognition is the real strength of human intelligence
      and distinguishes it from artificial intelligence.

PMID- 29342705
TI  - Building machines that adapt and compute like brains.
AB  - Building machines that learn and think like humans is essential not only for
      cognitive science, but also for computational neuroscience, whose ultimate goal
      is to understand how cognition is implemented in biological brains. A new
      cognitive computational neuroscience should build cognitive-level and neural
      level models, understand their relationships, and test both types of models with
      both brain and behavioral data.

PMID- 29342706
TI  - Benefits of embodiment.
AB  - Physical competence is acquired through animals' embodied interaction with their
      physical environments, and psychological competence is acquired through situated
      interaction with other agents. The acquired neural models essential to these
      competencies are implicit and permit more fluent and nuanced behavior than
      explicit models. The challenge is to understand how such models are acquired and
      used to control behavior.

PMID- 29342707
TI  - Human-like machines: Transparency and comprehensibility.
AB  - Artificial intelligence algorithms seek inspiration from human cognitive systems
      in areas where humans outperform machines. But on what level should algorithms
      try to approximate human cognition? We argue that human-like machines should be
      designed to make decisions in transparent and comprehensible ways, which can be
      achieved by accurately mirroring human cognitive processes.

PMID- 29342708
TI  - Ingredients of intelligence: From classic debates to an engineering roadmap.
AB  - We were encouraged by the broad enthusiasm for building machines that learn and
      think in more human-like ways. Many commentators saw our set of key ingredients
      as helpful, but there was disagreement regarding the origin and structure of
      those ingredients. Our response covers three main dimensions of this
      disagreement: nature versus nurture, coherent theories versus theory fragments,
      and symbolic versus sub-symbolic representations. These dimensions align with
      classic debates in artificial intelligence and cognitive science, although,
      rather than embracing these debates, we emphasize ways of moving beyond them.
      Several commentators saw our set of key ingredients as incomplete and offered a
      wide range of additions. We agree that these additional ingredients are important
      in the long run and discuss prospects for incorporating them. Finally, we
      consider some of the ethical questions raised regarding the research program as a
      whole.

PMID- 29342709
TI  - The argument for single-purpose robots.
AB  - The argument by Lake et al. to create more human-like robots is, first,
      implausible and, second, undesirable. It seems implausible to me that a robot
      might have friends, fall in love, read Foucault, prefer Scotch to Bourbon, and so
      on. It seems undesirable because we already have 7 billion people on earth and
      don't really need more.

PMID- 29342710
TI  - Intelligent machines and human minds.
AB  - The search for a deep, multileveled understanding of human intelligence is
      perhaps the grand challenge for 21st-century science, with broad implications for
      technology. The project of building machines that think like humans is central to
      meeting this challenge and critical to efforts to craft new technologies for
      human benefit.

PMID- 29342711
TI  - Horses for courses: When acceptability judgments are more suitable than
      structural priming (and vice versa).
AB  - Although structural priming is often the most suitable paradigm, it sometimes
      misses effects that are detected by more sensitive acceptability-judgment tasks,
      thus yielding incorrect conclusions. For example, Branigan & Pickering's (B&P's)
      claim that "syntactic representations do not contain semantic information" (sect.
      2.1, para. 2), while supported by structural-priming studies of the passive, is
      undermined by an acceptability-judgment study of this construction.

PMID- 29342712
TI  - Microscopic and macroscopic approaches to the mental representations of second
      languages.
AB  - With a particular reference to second language (L2), we discuss (1) how
      structural priming can be used to tap into L2 representations and their
      relationships with first and target language representations; and (2) how complex
      networks additionally can be used to reveal the global and local patterning of L2
      linguistic features and L2 developmental trajectories.

PMID- 29342713
TI  - Structural priming can inform syntactic analyses of partially grammaticalized
      constructions.
AB  - Branigan & Pickering (B&P) argue successfully that structural priming provides
      valuable information for developing psychologically plausible syntactic and
      semantic theories. I discuss how their approach can be used to help determine
      whether partially grammaticalized constructions that have undergone semantic
      change also have undergone syntactic reanalysis. I then consider cases in which
      evidence from priming cannot distinguish between competing syntactic analyses.

PMID- 29342714
TI  - The limitations of structural priming are not the limits of linguistic theory.
AB  - Structural priming is a useful technique for testing the predictions of
      linguistic theories, but one cannot conclude anything definitively about the
      shape of those theories from any particular methodology.

PMID- 29342715
TI  - Don't shoot the giant whose shoulders we are standing on.
AB  - Structural priming is a sufficient but not a necessary condition for proving the
      existence of representations. Absence of evidence is not evidence of absence.
      Cognitive science relies on the legitimacy of positing representations and
      processes without "proving" every component. Also, psycholinguistics relies on
      other methods, including acceptability judgments, to find the materials for
      priming experiments in the first place.

PMID- 29342716
TI  - If priming is graded rather than all-or-none, can reactivating abstract
      structures be the underlying mechanism?
AB  - In our commentary on Branigan & Pickering (B&P), we start by arguing that the
      authors implicitly adopt several assumptions, the consequence of which is to make
      further claims necessary and/or sufficient. Crucially, the authors assume the
      existence of discrete units at various levels of linguistic granularity that then
      must be operated upon by combinatorial mechanisms and rules (i.e.,
      decomposition/recomposition). They further argue that structural priming provides
      a powerful tool to study abstract, structural representations. We provide
      evidence that priming effects in production are characterized better as graded
      than as all-or-none and that priming need not arise from a mechanism that
      (re)activates a shared but abstract internal structure.

PMID- 29342717
TI  - A usage-based cognitive linguistic (re-)interpretation of priming evidence.
AB  - Usage-based cognitive linguistic (UBCL) theories offer a unifying interpretation
      of the different (structural vs. [more] lexical) priming effects reported by
      Branigan & Pickering (B&P), and they provide an ideal basis for explaining
      contextual influences on priming. However, they also call into question B&P's
      claim that priming "provides evidence that is directly informative about mental
      representation" (sect. 1.5, para. 1).

PMID- 29342718
TI  - The logic of syntactic priming and acceptability judgments.
AB  - A critical flaw in Branigan & Pickering's (B&P's) advocacy of structural priming
      is the absence of a theory of priming. This undermines their claims about the
      value of priming as a methodology. In contrast, acceptability judgments enable
      clearer inferences about structure. It is important to engage thoroughly with the
      logic behind different structural diagnostics.

PMID- 29342719
TI  - Converging on a theory of language through multiple methods.
AB  - Assuming that linguistic representation has been studied only by linguists using
      grammaticality judgments, Branigan & Pickering (B&P) present structural priming
      as a novel alternative. We show that their assumptions are incorrect for
      cognitive-functional linguistics, exposing converging perspectives on
      form/meaning pairings between generativists and cognitive-functional linguists
      that we hope will spark the cross-disciplinary discussion necessary to produce a
      cognitively plausible model of linguistic representation.

PMID- 29342720
TI  - Don't forget the neurobiology: An experimental approach to linguistic
      representation.
AB  - Acceptability judgments are no longer acceptable as the holy grail for testing
      the nature of linguistic representations. Experimental and quantitative methods
      should be used to test theoretical claims in psycholinguistics. These methods
      should include not only behavior, but also the more recent possibilities to probe
      the neural codes for language-relevant representations.

PMID- 29342721
TI  - Acceptability judgments still matter: Deafness and documentation.
AB  - The target article's call to end reliance on acceptability judgments is
      premature. First, it restricts syntactic inquiry to cases were a semantically
      equivalent alternative is available. Second, priming studies require groups of
      participants who are linguistically homogenous and whose grammar is known to the
      researcher. These requirements would eliminate two major research areas:
      syntactic competence in d/Deaf individuals, and language documentation. (We
      follow the convention of using deaf to describe hearing levels, Deaf to describe
      cultural identity, and d/Deaf to include both. Our own work has focused on Deaf
      signers, but the same concerns could apply to other deaf populations.).

PMID- 29342722
TI  - Syntactic levels, lexicalism, and ellipsis: The jury is still out.
AB  - Structural priming data are sometimes compatible with several theoretical views,
      as shown here for three key theoretical claims. One reason is that prime
      sentences affect multiple representational levels driving syntactic choice.
      Additionally, priming is affected by further cognitive functions (e.g., memory).
      We therefore see priming as a useful tool for the investigation of linguistic
      representation but not the only tool.

PMID- 29342723
TI  - Structural priming supports grammatical networks.
AB  - As Branigan & Pickering (B&P) argue, structural priming has important
      implications for the theory of language structure, but these implications go
      beyond those suggested. Priming implies a network structure, so the grammar must
      be a network and so must sentence structure. Instead of phrase structure, the
      most promising model for syntactic structure is enriched dependency structure, as
      in Word Grammar.

PMID- 29342724
TI  - Action sequences instead of representational levels.
AB  - Despite enthusiastic agreement that experimental data are directly relevant for
      determining grammar architecture, we present one main objection to the
      conclusions that the authors draw from their results: The data are perfectly
      compatible - in fact, much more in line - with an alternative that does not rely
      on syntactic representations. Instead, it is processing actions whose activation
      for comprehension/production explains intra-/inter-speaker priming.

PMID- 29342725
TI  - What structural priming can and cannot reveal.
AB  - The nature of mental representations of linguistic expressions in relation to the
      time course from intention to articulation is a major issue. We discuss Branigan
      & Pickering's (B&P's) proposal to use structural priming to tap into this
      process. We show that their interpretation of their findings cannot be
      maintained. We reinterpret these results and suggest a revision of their
      conclusions.

PMID- 29342726
TI  - On the nature of structure in structural priming.
AB  - Like Branigan & Pickering (B&P), we agree that processing evidence is important
      for linguistic theorization; however, without much evidence of priming of
      hierarchical argument structure independent of linear ordering, the nature of
      "structure" in structural priming remains unclear. Consequently, it is an
      empirical question whether structural priming and acceptability judgments tap
      into cognitive processes of a similar nature.

PMID- 29342727
TI  - Structural priming, action planning, and grammar.
AB  - Structural priming is poorly understood and cannot inform accounts of grammar for
      two reasons. First, those who view performance as grammar + processing will
      always be able to attribute psycholinguistic data to processing rather than
      grammar. Second, structural priming may be simply an example of hysteresis
      effects in general action planning. If so, then priming offers no special insight
      into grammar.

PMID- 29342728
TI  - Moving beyond the priming of single-language sentences: A proposal for a
      comprehensive model to account for linguistic representation in bilinguals.
AB  - In their target article, Branigan & Pickering (B&P) briefly discuss bilingual
      language representation, focusing primarily on cross-language priming between
      single-language sentences. We follow up on this discussion by showing how
      structural priming drives real-life phenomena of bilingual language use beyond
      the priming of unilingual sentences and by arguing that B&P's account should be
      extended with a representation for language membership.

PMID- 29342729
TI  - Considering experimental and observational evidence of priming together, syntax
      doesn't look so autonomous.
AB  - We agree with Branigan & Pickering (B&P) that structural priming experiments
      should supplant grammaticality judgments for testing linguistic representation.
      However, B&P overlook a vast (corpus-)linguistic literature that converges with -
      but extends - the experimental findings. B&P conclude that syntax is functionally
      independent of the lexicon. We argue that a broader approach to priming reveals
      cracks in the facade of syntactic autonomy.

PMID- 29342730
TI  - Structural priming is most useful when the conclusions are statistically robust.
AB  - Branigan & Pickering (B&P) claim that the success of structural priming as a
      method should "end the current reliance on acceptability judgments." Structural
      priming is an interesting and useful phenomenon, but we are dubious that the
      effect is powerful enough to test many detailed claims about specific points of
      syntactic theory.

PMID- 29342731
TI  - Priming methods in semantics and pragmatics.
AB  - Structural priming is a powerful method to inform linguistic theories. We argue
      that this method extends nicely beyond syntax to theories of meaning. Priming,
      however, should still be seen as only one of the tools available for linguistic
      data collection. Specifically, because priming can occur at different,
      potentially conflicting levels, it cannot detect every aspect of linguistic
      representations.

PMID- 29342732
TI  - Can structural priming answer the important questions about language?
AB  - Structural priming makes a valuable contribution to psycholinguistics, but it
      taps into implicit memory representations and processes that may differ from what
      is deployed during online language processing. As a result, the strength of
      inductive inference regarding linguistic representation is rather limited. We
      question whether implicit memory for language can and should be equated with
      linguistic representation or with language processing.

PMID- 29342733
TI  - The syntax of priming.
AB  - Priming reflects the reactivation of processing routines that map strings of
      words onto semantic representations (and vice versa) without the mediation of
      syntactic structure, including the "flat structure" that Branigan & Pickering
      (B&P) propose. Key evidence for this claim comes from the possibility of priming
      relations involving subject-verb sequences, which are not syntactic constituents.

PMID- 29342734
TI  - Structural priming is not a Royal Road to representations.
AB  - Branigan & Pickering (B&P) propose that the structural priming paradigm is a
      Royal Road to linguistic representations of any kind, unobstructed by influences
      of psychological processes. In my view, however, they are too optimistic about
      the versatility of the paradigm and, more importantly, its ability to provide
      direct evidence about the nature of stored linguistic representations.

PMID- 29342735
TI  - Structural priming is a useful but imperfect technique for studying all
      linguistic representations, including those of pragmatics.
AB  - Structural priming is a useful tool for investigating linguistics
      representations. We argue that structural priming can be extended to the
      investigation of pragmatic representations such as Gricean enrichments. That is
      not to say priming is without its limitations, however. Interpreting a failure to
      observe priming may not be as simple as Branigan & Pickering (B&P) imply.

PMID- 29342736
TI  - The relationship between priming and linguistic representations is mediated by
      processing constraints.
AB  - Understanding the nature of linguistic representations undoubtedly will benefit
      from multiple types of evidence, including structural priming. Here, we argue
      that successfully gaining linguistic insights from structural priming requires us
      to better understand (1) the precise mappings between linguistic input and
      comprehenders' syntactic knowledge; and (2) the role of cognitive faculties such
      as memory and attention in structural priming.

PMID- 29342737
TI  - Priming is swell, but it's far from simple.
AB  - Clearly, structural priming is a valuable tool for probing linguistic
      representation. But we don't think that the existing results provide strong
      support for Branigan & Pickering's (B&P's) model, largely because the priming
      effects are more confusing and diverse than their theory would suggest.
      Fortunately, there are a number of other experimental tools available, and
      linguists are increasingly making use of them.

PMID- 29342738
TI  - Developmental psycholinguistics teaches us that we need multi-method, not single
      method, approaches to the study of linguistic representation.
AB  - In developmental psycholinguistics, we have, for many years, been generating and
      testing theories that propose both descriptions of adult representations and
      explanations of how those representations develop. We have learnt that
      restricting ourselves to any one methodology yields only incomplete data about
      the nature of linguistic representations. We argue that we need a multi-method
      approach to the study of representation.

PMID- 29342739
TI  - The malleability of linguistic representations poses a challenge to the priming
      based experimental approach.
AB  - Recent findings show that experience with a syntactic structure has long-term
      consequences for how that structure will be processed in the future, which
      suggests that linguistic representations are not static entities that can be
      probed reliably without alteration. Thus, leveraging the effect of previous
      exposure to a syntactic structure appears to be an inappropriate method for
      studying invariant properties of language.

PMID- 29342740
TI  - Setting the empirical record straight: Acceptability judgments appear to be
      reliable, robust, and replicable.
AB  - Branigan & Pickering (B&P) advocate the use of syntactic priming to investigate
      linguistic representations and argue that it overcomes several purported
      deficiencies of acceptability judgments. While we recognize the merit of drawing
      attention to a potentially underexplored experimental methodology in language
      science, we do not believe that the empirical evidence supports B&P's claims
      about acceptability judgments. We present the relevant evidence.

PMID- 29342741
TI  - Structural priming and the representation of language.
AB  - Structural priming offers a powerful method for experimentally investigating the
      mental representation of linguistic structure. We clarify the nature of our
      proposal, justify the versatility of priming, consider alternative approaches,
      and discuss how our specific account can be extended to new questions as part of
      an interdisciplinary programme integrating linguistics and psychology as part of
      the cognitive sciences of language.

PMID- 29342742
TI  - Public health interventions can increase objective and perceived control by
      supporting people to enact the choices they want to make.
AB  - "Low-agency" public health interventions do not rely on individuals using their
      personal resources to benefit. These help people enact the choices they wish to
      make and are likely to increase objective and perceived control. Lower-agency
      interventions have been criticised as constraining individual choice. Pepper &
      Nettle show that this is unlikely to be the case.

PMID- 29342743
TI  - The elusive constellations of poverty.
AB  - Pepper & Nettle describe possible processes underlying what they call a
      behavioral constellation of deprivation (BCD). Although we are certain about the
      application of evolutionary models to our understanding of poverty, we are less
      certain about the utility of behavioral constellations. The empirical record on
      poverty-related behaviors is much more divergent and broad than such
      constellations suggest.

PMID- 29342744
TI  - From perceived control to self-control, the importance of cognitive and emotional
      resources.
AB  - Pepper & Nettle (P&N) suggest that the poor present a "contextually appropriate
      response" to a perceived limited control and to a short life expectancy. We argue
      that differences in health, behavior, or impaired economic decisions are better
      explained by self-control. We discuss the implications of the differences between
      these perspectives and present supporting findings from two intervention studies
      with marginalized populations.

PMID- 29342745
TI  - The behavioural constellation of deprivation: Compelling framework, messy
      reality.
AB  - Pepper & Nettle's (P&N's) argument is compelling, but apparently contradictory
      data are easily found. Associations between socioeconomic status (SES) and
      substance abuse are sometimes positive, the poor are sometimes eager to educate
      their children, and perceptions of local mortality risk can be so distorted as to
      constitute an implausible basis for contextually appropriate responding. These
      anomalies highlight the need for more psychological work.

PMID- 29342746
TI  - The behavioral constellation of deprivation may be best understood as risk
      management.
AB  - Although the authors make a compelling case that early-life deprivation leads to
      present orientation, we believe that such behaviors may be better understood in
      terms of an underlying risk-management strategy, in which those who experience
      such deprivation are more risk-averse. The model we sketch accommodates the
      authors' present-orientation observations and further explains differences in
      risk preferences and social preferences.

PMID- 29342747
TI  - Developing the behavioural constellation of deprivation: Relationships, emotions,
      and not quite being in the present.
AB  - Although it is a welcome and timely idea, the behavioural constellation of
      deprivation (BCD) needs to explain how the development of personal control,
      trust, and perception of future risk is mediated through relationships with
      parents. Further, prioritising the present over the future may not be the essence
      of this constellation; perhaps not quite being, either in the present or in the
      future, is a better depiction.

PMID- 29342748
TI  - Interpreting risky behavior as a contextually appropriate response: Significance
      and policy implications beyond socioeconomic status.
AB  - The significance of the contextually appropriate response perspective (CARP) can
      be judged, in part, by its potential to stimulate new research and guide public
      policy. To illustrate this potential, I move beyond socioeconomic status
      differences in behavior and apply CARP to broader, policy-relevant issues in
      criminology. In this area, CARP sheds new light on some old problems.

PMID- 29342749
TI  - Evolutionary approaches to deprivation transform the ethics of policy making.
AB  - When designing public policies, decision makers often rely on their own
      behavioral preferences. Pepper & Nettle's (P&N's) theory suggests that these
      preferences are unlikely to be appropriate when applied to a different
      environment (e.g., a low-income environment with fewer career opportunities).
      This theory has profound implications for the design and ethics of public
      policies.

PMID- 29342750
TI  - The physiological constellation of deprivation: Immunological strategies and
      health outcomes.
AB  - Physiology and behavior are best thought of as two aspects of the same biological
      process, shaped simultaneously by natural selection. Like behavioral strategies,
      ecological conditions may affect physiological strategies, leading to changes in
      immunity and hormonal regulation. These alternate strategies help explain the
      health correlations of deprivation and provide additional pathways for feedback
      from early-life experiences.

PMID- 29342751
TI  - Divergent life histories and other ecological adaptations: Examples of social
      class differences in attention, cognition, and attunement to others.
AB  - Many behavioral and psychological effects of socioeconomic status (SES), beyond
      those presented by Pepper & Nettle cannot be adequately explained by life-history
      theory. We review such effects and reflect on the corresponding ecological
      affordances and constraints of low- versus high-SES environments, suggesting that
      several ecology-specific adaptations, apart from life-history strategies, are
      responsible for the behavioral and psychological effects of SES.

PMID- 29342752
TI  - Uncertainty about future payoffs makes impatience rational.
AB  - Uncertainty (i.e., variable payoffs with unknown probabilities) brings together a
      number of features of the authors' argument. It leads to present bias, even for
      completely rational agents with time-consistent preferences. As an evolutionary
      product of Pleistocene climate instability, humans possess broad adaptations to
      environmental uncertainty, giving rise to key features of the behavioral
      constellation of deprivation (BCD).

PMID- 29342753
TI  - Beyond personal control: The role of developing self-control abilities in the
      behavioral constellation of deprivation.
AB  - We agree with Pepper & Nettle that personal control is important in understanding
      people's willingness to engage in future-oriented behavior. However, this does
      not imply that self-control abilities play no role, for self-control abilities do
      influence whether individuals engage in future-oriented behavior. Personal
      control may also shape the development of self-control abilities, so contrasting
      the two may be a false dichotomy.

PMID- 29342754
TI  - Toward a balanced view of stress-adapted cognition.
AB  - Pepper & Nettle's paper exemplifies an emerging resistance against an exclusive
      focus on deficits in people who come from harsh environments. We extend their
      model by arguing for a perspective that includes not only contextually
      appropriate responses but also strengths - that is, enhanced mental skills and
      abilities. Such a well-rounded approach can be leveraged in education, jobs, and
      interventions.

PMID- 29342755
TI  - What about the behavioral constellation of advantage?
AB  - Many short-sighted behaviors are more common among poorer people. These behaviors
      are neither evolutionarily nor historically unusual and have strong contemporary
      encouragement. The bigger puzzle is their lower frequency among the affluent. The
      behaviors also have clear cultural and normative aspects that limit the
      usefulness of strictly individualist theories.

PMID- 29342756
TI  - Predictability or controllability: Which matters more for the BCD?
AB  - Pepper & Nettle's theory of the behavioral constellation of deprivation (BCD)
      would benefit from teasing apart the conceptually distinct - although related -
      constructs of predictability and control. Our commentary draws from prior
      research conducted in the learning domain to demonstrate that predictability
      moderates the effects of control and independently exerts a powerful influence on
      outcomes relevant to the BCD.

PMID- 29342757
TI  - Socioeconomic status, unpredictability, and different perceptions of the same
      risk.
AB  - In this commentary, we address three questions: (1) How might outcomes be
      affected by the variation in the level of deprivation, rather than the average
      level of deprivation? (2) Could there be differences in the subjective perception
      of the same risk as either intrinsic or extrinsic, depending on people's
      socioeconomic status (SES)? (3) What other psychological mechanisms might play a
      role in influencing the psychology and behavior of people from deprived
      backgrounds?

PMID- 29342758
TI  - When does deprivation motivate future-oriented thinking? The case of climate
      change.
AB  - Pepper & Nettle overstate cross-domain evidence of present-oriented thinking
      among lower-socioeconomic-status (SES) groups and overlook key social and
      contextual drivers of temporal decision making. We consider psychological
      research on climate change - a quintessential intertemporal problem that
      implicates inequities and extrinsic mortality risk - documenting more future
      oriented thinking among low- compared to high-SES groups.

PMID- 29342759
TI  - Loss of control is not necessary to induce behavioral consequences of
      deprivation: The case of religious fasting during Ramadan.
AB  - Pepper & Nettle argue that the more present-oriented behavior associated with a
      low socioeconomic status is an adaptive response to having relatively little
      control over the future. However, a study of fasters during Ramadan shows that
      self-imposed deprivation, which carries no implications regarding the ability to
      realize deferred rewards, is associated with loss and risk aversion.

PMID- 29342760
TI  - The uncontrollable nature of early learning experiences.
AB  - Early learning experiences shape the development of the behavioral constellation
      of deprivation (BCD) proposed by Pepper & Nettle (P&N). There is considerable
      variability in early learning experiences across diverse socioeconomic status
      (SES) backgrounds, particularly when it comes to language. Here, we discuss how
      early learning experiences are beyond the control of the individual and
      subsequently contribute to behaviors in P&N's constellation.

PMID- 29342761
TI  - The "appropriate" response to deprivation: Evolutionary and ethical dimensions.
AB  - Pepper & Nettle use an evolutionary framework to argue that "temporal
      discounting" is an appropriate response to low socioeconomic status (SES), or
      deprivation. We suggest some conceptual refinements to their "appropriate
      response" perspective, with the hope that it usefully informs future research on
      and public policy responses to the relationship between deprivation and temporal
      discounting.

PMID- 29342762
TI  - Both collection risk and waiting costs give rise to the behavioral constellation
      of deprivation.
AB  - Pepper & Nettle explain the behavioral constellation of deprivation (BCD) in
      terms of differences in collection risk (i.e., the probability of collecting a
      reward after some delay) between high- and low-socioeconomic-status (SES)
      populations. We argue that a proper explanation should also include the costs of
      waiting per se, which are paid even when the benefits are guaranteed.

PMID- 29342763
TI  - Relative state, social comparison reactions, and the behavioral constellation of
      deprivation.
AB  - Pepper & Nettle compellingly synthesize evidence indicating that temporal
      discounting is a functional, adaptive response to deprivation. In this
      commentary, we underscore the importance of the psychology of relative state,
      which is an index of relative competitive (dis)advantage. We then highlight two
      proximate emotional social comparison reactions linked with relative state -
      personal relative deprivation and envy - that may play an important role in the
      deprivation-discounting link.

PMID- 29342764
TI  - Cultural consonance, deprivation, and psychological responses for niche
      construction.
AB  - Cultural consonance is a measure of culturally encoded goals relevant to
      psychological, behavioral, and health responses to deprivation. Similar to
      extrinsic mortality, low cultural consonance and an associated inability to
      predict adaptive outcomes may activate impulsivity, delay discounting, and reward
      seeking. Low cultural consonance could promote "fast life history" in low-quality
      environments and motivate cultural niche construction for local adaptation.

PMID- 29342765
TI  - Stuff goes wrong, so act now.
AB  - Pepper & Nettle make an ambitious and compelling attempt to isolate a common
      cause of what they call the behavioral constellation of deprivation. We agree
      with the authors that limited control can indeed help explain part of the
      difference in observed present-oriented behavior between the poor and the rich.
      However, we suggest that mortality risk is not the primary mechanism leading to
      this apparent impatience.

PMID- 29342766
TI  - Deprived, but not depraved: Prosocial behavior is an adaptive response to lower
      socioeconomic status.
AB  - Individuals of lower socioeconomic status (SES) display increased attentiveness
      to others and greater prosocial behavior compared to individuals of higher SES.
      We situate these effects within Pepper & Nettle's contextually appropriate
      response framework of SES. We argue that increased prosocial behavior is a
      contextually adaptive response for lower-SES individuals that serves to increase
      control over their more threatening social environments.

PMID- 29342767
TI  - It's not just about the future: The present payoffs to behaviour vary in degree
      and kind between the rich and the poor.
AB  - Pepper & Nettle offer a nuanced and humane view on poverty that should be
      required reading for policy makers, particularly those interested in "behaviour
      change" policy. We suggest, however, that the emphasis on "future-discounting" in
      this paper downplays the importance of differences in the payoffs to behaviours
      in the present and how these payoffs may be realised in different currencies.

PMID- 29342768
TI  - Intertemporal impulsivity can also arise from persistent failure of long-term
      plans.
AB  - We suggest that steep intertemporal discounting in individuals of low
      socioeconomic status (SES) may arise as a rational metacognitive adaptation to
      experiencing planning and control failures in long-term plans. Low SES
      individuals' plans fail more frequently because they operate close to budgetary
      boundaries, in turn because they consistently operate with limited budgets of
      money, status, trust, or other forms of social utility.

PMID- 29342769
TI  - The link between deprivation and its behavioural constellation is confounded by
      genetic factors.
AB  - Most research cited throughout Pepper & Nettle's (P&N's) target article is
      correlational and suffers from a serious genetic confound that renders it of
      little evidentiary value. Of correlational findings that are not confounded, P&N
      ignore examples that contradict their model. Further, P&N's claim that
      evolutionary models explaining between-species differences in behaviour can be
      used to understand that corresponding individual differences lack any evidence.

PMID- 29342770
TI  - Health behaviour, extrinsic risks, and the exceptions to the rule.
AB  - Pepper & Nettle make a compelling case for how evolutionary thinking can help
      explain behaviours that cluster with deprivation. The role of extrinsic mortality
      risk in driving behaviour is probably important, but strong evidence is still
      lacking. By thinking carefully about behaviours seemingly at odds with an
      evolutionary life history perspective, we can gain important insights that will
      help refine theory.

PMID- 29342771
TI  - Intergenerational capital flows are central to fitness dynamics and adaptive
      evolution in humans.
AB  - Human fitness dynamics are uniquely and profoundly governed by the flow of
      capital to subsequent generations. Low socioeconomic status individuals may
      possess limited capacity to direct capital to descendants and may respond to such
      constraints adaptively or maladaptively. Mitigation of capital constraints may
      provide practicable routes to alleviation of the behavioural constellation of
      deprivation.

PMID- 29342772
TI  - Epigenetic-based hormesis and age-dependent altruism: Additions to the
      behavioural constellation of deprivation.
AB  - We support Pepper and Nettle's (P&N's) hypothesised adaptive responses to
      deprivation. However, we argue that adaptive responses to stress shift with age.
      Specifically, present-oriented behaviours are adaptive for young people (e.g., in
      terms of mating and reproduction) but costly for older people in deprived
      communities who would benefit from investing in grandchildren. Epigenetic
      mechanisms may be responsible for age-related tactical shifts.

PMID- 29342773
TI  - Strengths, altered investment, risk management, and other elaborations on the
      behavioural constellation of deprivation.
AB  - We are grateful to have received so many insightful commentaries from interested
      colleagues regarding our proposed behavioural constellation of deprivation (BCD)
      and our thoughts on its causes and consequences. In this response article, we
      offer some clarifications regarding our perspective and tackle some common
      misperceptions, including, for example, assumptions that the BCD is adaptive and
      that it should include all behaviours that vary with socioeconomic status. We
      then welcome some excellent proposals for extensions and modifications of our
      ideas, such as the conceptualisation of the BCD as a risk-management strategy and
      the calls for a greater focus on strengths and differential investment rather
      than deficits and disinvestment. Finally, we highlight some insightful
      explorations of the implications of our ideas for ethics, policy, and practice.

PMID- 29342774
TI  - A social dimension to enjoyment of negative emotion in art reception.
AB  - The proposed model overlooks the contribution of a relational/prosocial dimension
      to the enjoyment of negative emotion in art reception. Negative experiences have
      a unique capacity to build social bonds and may also increase motivation to
      "connect" with the artist. This affiliative motivation ensures that people
      experience an artwork as more emotional, more intense, more interesting, and
      ultimately more rewarding.

PMID- 29342775
TI  - Artistic misunderstandings: The emotional significance of historical learning in
      the arts.
AB  - The Distancing-Embracing model does not have the conceptual resources to explain
      artistic misunderstandings and the emotional consequences of historical learning
      in the arts. Specifically, it suggests implausible predictions about emotional
      distancing caused by art schemata (e.g., misunderstandings of artistic intentions
      and contexts). These problems show the need for further inquiries into how
      historical contextualization modulates negative emotions in the arts.

PMID- 29342776
TI  - Reconciling an underlying contradiction in the Distancing-Embracing model.
AB  - The Distancing-Embracing model proposes that negative emotions embedded in
      literary works can be rewarding. This is consistent with a holistic ontology in
      the German Romantic tradition. However, the application of cognitive psychology
      to explain experiences of aesthetic pleasure is problematic because it is founded
      on a mechanistic Enlightenment epistemology. The appreciation of negative
      emotions requires cognitive elaboration and closure, whereas hedonistic reward is
      contingent on the reader's needs, in the moment, for pleasure or distraction.

PMID- 29342777
TI  - Positivity versus negativity is a matter of timing.
AB  - "Negative" emotions are never purely negative. They attract attention at the very
      least and often stay attractive enough to make rehearsing them an addictive
      activity. As the authors point out, they also counteract a relentless tendency
      for positive emotions to become boring. Analysis in terms of reward suggests why
      this tendency occurs and how symbiosis with negative emotions may arise, in art
      and in life.

PMID- 29342778
TI  - Considering the filmmaker: Intensified continuity, narrative structure, and the
      Distancing-Embracing model.
AB  - Menninghaus et al. pose two open-ended questions: To what extent do formal
      elements of art elicit negative affect, and do artists try to elicit this
      response in a theory-based or intuitive manner? For popular movies, we argue that
      the consideration of their construction is prior to the consideration of the
      experience that they evoke.

PMID- 29342779
TI  - Emotional granularity and the musical enjoyment of sadness itself.
AB  - We contest the claim that musically induced sadness cannot be enjoyable in
      itself. This possibility is supported by closer attention to a musical experience
      as well as cases of affective reversal, such as the "hedonic flip" of painful
      feelings. We propose that the affective reversal of sadness in music is due to
      the high granularity of musically induced emotion.

PMID- 29342780
TI  - The urge to judge: Why the judgmental attitude has anything to do with the
      aesthetic enjoyment of negative emotions.
AB  - Based on arguments from both philosophical and empirical aesthetics, we hereby
      propose that the enjoyment of negative emotions in art and fiction is distinct
      from the immediate pleasure deriving from sensory features, because it requires a
      conscious, intentional attitude toward the object. This attitude is linked with
      the compelling goal of providing a judgment of liking, beauty, perfection, or
      similar.

PMID- 29342781
TI  - Orange is the new aesthetic.
AB  - The Distancing-Embracing model proposes that negative emotions are constitutive
      of aesthetic experiences. This move is welcome and adds depth to empirical
      aesthetics. However, the model's emphasis on temporality challenges how best to
      think of static art forms. I suggest that "decisive" and "distilled" moments
      dilate time in the viewer's mind and might allow the model to accommodate
      photography and painting.

PMID- 29342782
TI  - Distancing, not embracing, the Distancing-Embracing model of art reception.
AB  - Despite denials in the target article, the Distancing-Embracing model appeals to
      compensatory ideas in explaining the appeal of artworks that elicit negative
      affect. The model also appeals to the deflationary effects of psychological
      distancing. Having pointed to the famous rejection in the 1960s of the view that
      aesthetic experience involves psychological distancing, I suggest that "distance"
      functions here as a weak metaphor that cannot sustain the explanatory burden the
      theory demands of it.

PMID- 29342783
TI  - Boredom in art.
AB  - In the light of recent findings on the nature of boredom, I argue that boredom is
      a potentially useful emotion in art reception and show how the Distancing
      Embracing model can be applied to boredom.

PMID- 29342784
TI  - You are not alone - Social sharing as a necessary addition to the Embracing
      factor.
AB  - I argue that the Embracing factor cannot be adequately conceptualized without
      taking into account the regulatory power of the social sharing of emotions.
      Humans tend to share their negative emotions with close others, and they benefit
      from it. I outline how this mechanism works in art reception by regulating and
      transforming negative emotions into positive experiences.

PMID- 29342785
TI  - Individual differences in embracing negatively valenced art: The roles of
      openness and sensation seeking.
AB  - We elaborate on the role of individual differences in the processing mechanisms
      outlined by the Distancing-Embracing model. The role of openness is apparent in
      appreciating meaning-making art that elicits interest, feeling moved, and mixed
      emotions. The influence of sensation seeking is likely to manifest in thrill
      chasing art that draws on the arousing interplay of positive and negative
      emotions.

PMID- 29342786
TI  - Fiction as a bridge to action.
AB  - We propose an extension of the Distancing-Embracing model to the use of stories
      for prosocial ends. Specifically, audiences may find stories of individuals in
      need too emotionally overwhelming. Audiences may attempt to regulate or reduce
      negative emotions, which can reduce empathy and willingness to help. Through
      distancing, fictionalized accounts may counteract this tendency and thus increase
      prosocial behavior.

PMID- 29342787
TI  - Empathy as a guide for understanding the balancing of Distancing-Embracing with
      negative art.
AB  - We connect the Distancing-Embracing model to theoretical and empirical evidence
      regarding empathy, which raises questions about the ordering and modulation of
      distancing in particular. Namely, distancing may not be a binary, continuously
      on/off process. Rather we suggest that changes in distancing as actualized via
      the relation between the individual and art (e.g., through empathy) might be a
      useful avenue for further consideration.

PMID- 29342788
TI  - Live theatre as exception and test case for experiencing negative emotions in
      art.
AB  - Distancing and then embracing constitutes a useful way of thinking about the
      paradox of aesthetic pleasure. However, the model does not account for live
      theatre. When live actors perform behaviors perceptually close to real life and
      possibly really experienced by the actors, audiences may experience autonomic
      reactions, with less distance, or may have to distance post
      experiencing/embracing their emotions.

PMID- 29342789
TI  - Art enhances meaning by stimulating integrative complexity and aesthetic
      interest.
AB  - Menninghaus et al. portrayed meaning in art as a vehicle for transforming
      negative emotions into pleasure. Although it is intuitively appealing that
      meaningful experiences should feel good, meaningfulness does not necessarily
      entail pleasure or positive emotions. Whereas easily comprehended art may elicit
      pleasure, meaningfulness is more closely tied to challenge and interest than to
      pleasure.

PMID- 29342790
TI  - Context matters: How macroeconomic forces may alter the reception of negative
      emotions in art.
AB  - Menninghaus et al. offer a comprehensive model to explain why people pursue
      darker emotions in art, but we believe they underplay the considerable role of
      situational factors in driving these preferences. In particular, changing mood
      states are likely to shape artistic preferences, in large part because positive
      mood states act as a protective buffer against otherwise aversive experiences.

PMID- 29342791
TI  - "Negative emotions" live in stories, not in the hearts of readers who enjoy them.
AB  - The commendably ambitious project by Menninghaus et al. fails because its main
      connective tissue - "negative emotions" - is beyond the grasp of the authors'
      largely literary approach. The critique focuses on their treatment of the Paradox
      of Fiction, the neglect of the biological, adaptive nature of emotions, and the
      absence of convincing empirical support for key aspects of the proposed model.

PMID- 29342792
TI  - What is art and how does it differ from aesthetics?
AB  - Art objects differ from other objects because they are intentionally created to
      embody a producer's (i.e., artist's) expression. Hence, art objects are social
      objects whose appeal and value are determined largely by the strategic
      interaction between the artist and the audience. I discuss several aspects of how
      strategic interaction can affect an art object's perceived value and aesthetic
      appeal.

PMID- 29342793
TI  - The paradox of tragedy and emotional response to simulation.
AB  - The insightful analysis of Menninghaus et al. could be deepened and rendered more
      systematic by recognizing that our emotional enjoyment of tragedy - and our
      response to fiction more generally - are versions of what happens with
      simulation. They derive from the operation and evolutionary function of
      simulation. Once we understand emotion in simulation, we largely understand
      emotion in tragedy (and fiction).

PMID- 29342794
TI  - The enjoyment of negative emotions in the experience of magic.
AB  - Theatrical magic is designed to elicit negative emotions such as feelings of
      vulnerability, loss of control, apprehension, fear, confusion, and bafflement.
      This commentary suggests that the Distancing-Embracing model can help us
      understand how the experience of magic can be aesthetically pleasurable, not
      despite, rather thanks to, some of the strong negative emotions it provokes.

PMID- 29342795
TI  - Psychological models of art reception must be empirically grounded.
AB  - We commend Menninghaus et al. for tackling the role of negative emotions in art
      reception. However, their model suffers from shortcomings that reduce its
      applicability to empirical studies of the arts: poor use of evidence, lack of
      integration with other models, and limited derivation of testable hypotheses. We
      argue that theories about art experiences should be based on empirical evidence.

PMID- 29342796
TI  - Art and fiction are signals with indeterminate truth values.
AB  - Menninghaus et al. distinguish art from fiction, but no current arguments or data
      suggest that the concept of art can be meaningfully circumscribed. This is a
      problem for aesthetic psychology. I sketch a solution by rejecting the
      distinction: Unlike most animal communication, in which signals are either true
      or false, art and fiction consist of signals without determinate truth values.

PMID- 29342797
TI  - Does art expertise facilitate distancing?
AB  - With respect to the Distancing-Embracing model, we discuss whether experts with
      well-developed and highly accessible schemata that lend themselves to distancing
      have initial affective reactions similar to those of novices, who lack access to
      well-developed distancing mechanisms, and whether differences between experts'
      and novices' responses are apparent only after distancing mechanisms have had a
      chance to do their work. We revisit findings from Leder et al. (2014) and discuss
      the role of mixed emotions and fluency.

PMID- 29342798
TI  - Art as emotional exploration.
AB  - The Roman poet Horace said poetry gives pleasure and instructs. A more
      informative theory is that poetry and art, in general, are less about pleasure
      than about exploration of emotions. Literary authors concentrate on negative
      emotions, seemingly to try and understand them. In two studies, reading literary
      art enabled the transformation of selfhood, not by being instructed but by people
      changing in their own ways.

PMID- 29342799
TI  - Being moved is a positive emotion, and emotions should not be equated with their
      vernacular labels.
AB  - As evidence for the second process of the Embracing factor, the target article
      characterizes being moved as a mixed emotion linked to sadness through metonymy.
      We question these characterizations and argue that emotions should not be equated
      with their vernacular labels.

PMID- 29342800
TI  - Genre scripts and appreciation of negative emotion in the reception of film.
AB  - The Distancing-Embracing model reserves a role for genre scripts in the hedonic
      valuation of negative emotion in art. Genre scripts, as defined in the target
      article, leave higher-level recipient intuitions out of scope. We argue that, in
      film genre scripts, lower-level stylistic features lend access to more complex
      conceptual knowledge, including pragmatic principles. The argument implies a
      consideration of the communicative dimension of aesthetic works, which could
      strengthen both factors of the Distancing-Embracing model.

PMID- 29342801
TI  - Parental response to baby cry involves brain circuits for negative emotion
      Distancing-Embracing.
AB  - The "art form" of parent-infant bonding critically involves baby conveying
      negative emotions - literally compelling parents to respond and provide care.
      Current research on the brain basis of parenting is combining brain imaging with
      social, cognitive, and behavioral analyses to understand how parental brain
      circuits regulate thoughts and behavior in mental health, risk, and resilience.
      Understanding the parental brain may contribute to solving the long-standing
      paradox of self-sought hedonic exposure to negative emotions in art reception.

PMID- 29342802
TI  - Art reception as an interoceptive embodied predictive experience.
AB  - In the Distancing-Embracing model, an explanation is proposed for the apparent
      paradox that is the enjoyment of negative emotional states in art reception.
      Here, we argue for the advantages of grounding the psychological dynamics
      described in the model in established and empirically testable frameworks of
      brain functioning by thinking of art reception as an embodied experience guided
      by predictive coding.

PMID- 29342803
TI  - Explaining the enjoyment of negative emotions evoked by the arts: The need to
      consider empathy and other underlying mechanisms of emotion induction.
AB  - Any model aiming to explain the enjoyment of negative emotions in the context of
      the arts should consider how works of art are able to induce emotional responses
      in the first place. For instance, research on empathy and the arts suggests that
      the psychological processes that mediate the enjoyment of sadness and horror may
      be fundamentally different.

PMID- 29342804
TI  - Tuning in to art: A predictive processing account of negative emotion in art.
AB  - We use the example of art-derived solace to discuss a broader mechanism by which
      negative affect is instrumental in creating positive appreciation of artworks.
      Based on the theory of predictive processing, we argue that increasing attunement
      or reduction of prediction errors, which implies increasing validation of the
      agents (models), is experienced as positive, even if the artwork's content is
      negative.

PMID- 29342805
TI  - Embracing nonfiction: How to extend the Distancing-Embracing model.
AB  - The Distancing factor of Menninghaus et al.'s model includes schemas that remind
      consumers that the representation is fictional. Although they claim that these
      schemas are crucial to the functioning of the Embracing factor of the model, we
      argue that consumers can have similar responses to nonfictional representations.
      We urge the authors to expand their model to include such cases.

PMID- 29342806
TI  - Negative emotions in art reception: Refining theoretical assumptions and adding
      variables to the Distancing-Embracing model.
AB  - While covering all commentaries, our response specifically focuses on the
      following issues: How can the hypothesis of emotional distancing (qua art
      framing) be compatible with stipulating high levels of felt negative emotions in
      art reception? Which concept of altogether pleasurable mixed emotions does our
      model involve? Can mechanisms of predictive coding, social sharing, and immersion
      enhance the power of our model?

PMID- 29342807
TI  - Beyond aerodigestion: Exaptation of feeding-related mouth movements for social
      communication in human and nonhuman primates.
AB  - Three arguments are advanced from human and nonhuman primate infancy research for
      the exaptation of ingestive mouth movements (tongue protrusion and lip smacking)
      for the purposes of social communication: their relation to affiliative
      behaviours, their sensitivity to social context, and their role in social
      development. Although these behaviours may have an aerodigestive function, such
      an account of their occurrence is only partial.

PMID- 29342808
TI  - Philosopher's disease and its antidote: Perspectives from prenatal behavior and
      contagious yawning and laughing.
AB  - Accounts of behavior, including imitation, often suffer from philosopher's
      disease: the unnecessary, inappropriate, theoretically driven explanation of
      behavior in terms of cognition, rationality, and consciousness. Embryos are
      perversely unphilosophical and unpsychological, starting to move before they
      receive sensory input. Postnatal contagious yawning and laughing indicate that
      pseudo-imitative behavior can occur without conscious intent or other higher
      order cognitive process.

PMID- 29342809
TI  - Beyond sensorimotor imitation in the neonate: Mentalization psychotherapy in
      adulthood.
AB  - Despite the persuasiveness of Keven & Akins' (K&A) review, we argue that
      mentalization, or the ability to interpret the mental states of oneself and
      others, is required to construct the neonate mind, going far beyond sensorimotor
      imitation. This concept, informed by certain psychoanalytic and attachment
      theories, has produced a form of therapy called mentalization-based
      psychotherapy, which aims to improve emotional regulation. Our aim here is to
      shed light on a form of neonatal imitation that goes beyond sensorimotor
      imitation.

PMID- 29342810
TI  - "It takes two to know one" - Tongue protrusion-retraction is only one small facet
      of early intersubjectivity.
AB  - Tongue protrusion-retraction is critical to early nutrition but is also a
      gustatory-olfactory aspect of early infant social behaviour that is, in part,
      reliant on pre-natal exposure and learning. Most early development is necessarily
      dyadic and intrinsically associated with other aspects of social functioning.

PMID- 29342811
TI  - Spontaneous communication and infant imitation.
AB  - Infant behavior is viewed in a social-communicative context centered on the
      phenomenon of spontaneous communication. Symbolic communication is learned and
      culturally structured, intentional, consists of symbols, and is propositional in
      content. In contrast, spontaneous communication is innate in both its sending
      (display) and receiving (preattunement) aspects, non-intentional, consists of
      signs, and is non-propositional or emotional in content. It underlies infant
      imitation, interactional synchrony, primary intersubjectivity, emotional empathy,
      and mirror neurons; and it is associated with oxytocin.

PMID- 29342812
TI  - A major blow to primate neonatal imitation and mirror neuron theory.
AB  - Keven & Akins' (K&A's) compelling new hypothesis explaining the developmental and
      neural basis of neonatal tongue protrusion has important implications for current
      understanding of primate imitation and the explanatory value of mirror neurons.
      If correct, this hypothesis eliminates a major source of evidence for neonatal
      imitation. I explore the implications this has for mirror neuron research and the
      arguments building upon them.

PMID- 29342813
TI  - Mommy or me? Who is the agent in a sense of agency in infant orofacial
      stereotypies?
AB  - That neonates imitate is an assertion that lacks supporting evidence. Orofacial
      stereotypies are critical to optimizing food rejection. Matching of tongue
      protrusion is not imitation, but a manifestation of the infant's arousal by the
      modeler's exhibition of the same behavior. The support for the nativist assertion
      that newborn infants imitate is not compelling, and we should proceed on the
      assumption that they do not.

PMID- 29342814
TI  - Do innate stereotypies serve as a basis for swallowing and learned speech
      movements?
AB  - Keven & Akins suggest that innate stereotypies like TP/R may participate in the
      acquisition of tongue control. This commentary examines this claim in the context
      of speech motor learning and biomechanics, proposing that stereotypies could
      provide a basis for both swallowing and speech movements, and provides
      biomechanical simulation results to supplement neurological evidence for
      similarities between the two behaviors.

PMID- 29342815
TI  - Infant orofacial movements: Inputs, if not outputs, of early imitative ability?
AB  - According to Keven & Akins (K&A), infant orofacial gestures may not reflect
      imitative responses. Here, we emphasise that these actions nonetheless represent
      a significant feature of the infant's early sensorimotor experience, and
      therefore may play a key role in the development of imitative capacities. We
      discuss how the ideas proposed in the target article could contribute
      substantially to experiential accounts of imitation.

PMID- 29342816
TI  - Animal studies help clarify misunderstandings about neonatal imitation.
AB  - Empirical studies are incompatible with the proposal that neonatal imitation is
      arousal driven or declining with age. Nonhuman primate studies reveal a
      functioning brain mirror system from birth, developmental continuity in imitation
      and later sociability, and the malleability of neonatal imitation, shaped by the
      early environment. A narrow focus on arousal effects and reflexes may grossly
      underestimate neonatal capacities.

PMID- 29342817
TI  - Beyond neonatal imitation: Aerodigestive stereotypies, speech development, and
      social interaction in the extended perinatal period.
AB  - In our target article, we argued that the positive results of neonatal imitation
      are likely to be by-products of normal aerodigestive development. Our hypothesis
      elicited various responses on the role of social interaction in infancy, the
      methodological issues about imitation experiments, and the relation between the
      aerodigestive theory and the development of speech. Here we respond to the
      commentaries.

PMID- 29342818
TI  - The functional and developmental role of imitation in the (a)typical brain.
AB  - Keven & Akins (K&A) propose a biologically plausible view of neonatal imitation
      based on the analysis of sensorimotor development. Here, we consider imitation in
      the general context of motor cognition, taking examples from both typical and
      atypical development. Specifically, we will discuss the functional role of
      imitation, its multi-level nature, and its anomalous features in autism.

PMID- 29342819
TI  - When dyadic interaction is the context: Mimicry behaviors on the origin of
      imitation.
AB  - Keven & Akins (K&A) redefine some of the neonatal imitation (NI) behaviors as
      developmental stereotypes. From a neuroconstructivist framework, those early
      gestures are also far from being considered as imitative behaviors. The cognitive
      substrate of imitation requires an interactive context to develop. Prior to
      intentional imitation, the dyad shows mimicry behaviors, which are automatic, but
      do not fade through development.

PMID- 29342820
TI  - There is no compelling evidence that human neonates imitate.
AB  - Keven & Akins (K&A) propose that neonatal "imitation" is a function of newborns'
      spontaneous oral stereotypies and should be viewed within the context of normal
      aerodigestive development. Their proposal is in line with the result of our
      recent large longitudinal study that found no compelling evidence for neonatal
      imitation. Together, these works prompt reconsideration of the developmental
      origin of genuine imitation.

PMID- 29342821
TI  - Multisensory control of ingestive movements and the myth of food addiction in
      obesity.
AB  - Some individuals have a neurogenetic vulnerability to developing strong
      facilitation of ingestive movements by learned configurations of biosocial
      stimuli. Condemning food as addictive is mere polemic, ignoring the
      contextualised sensory control of the mastication of each mouthful. To beat
      obesity, the least fattening of widely recognised eating patterns needs to be
      measured and supported.

PMID- 29342822
TI  - The case against newborn imitation grows stronger.
AB  - The claim that human newborns imitate is widely accepted and influential. Yet
      reliable evidence that newborns match modeled behaviors is limited, and there is
      no empirically based explanation of how the knowledge that imitation requires
      could develop before birth. In their target article, Keven & Akins (K&A)
      contribute important new evidence to an alternative account of newborns' matching
      that challenges the newborn imitation claim.

PMID- 29342823
TI  - Elements of a comprehensive theory of infant imitation.
AB  - Imitation is central to human development. Imitation involves mapping between the
      perception and production of actions. Imitation after delays implicates preverbal
      memory. Imitation of people informs us about infants' processing of social
      events. A comprehensive theory needs to account for the origins, mechanisms, and
      functions of imitation. Neonatal imitation illuminates how the initial state
      engenders and supports rapid social learning.

PMID- 29342824
TI  - Ecological validity, embodiment, and killjoy explanations in developmental
      psychology.
AB  - Keven & Akins (K&A) present a compelling alternative to the case for neonatal
      orofacial imitation, offered by Meltzoff and Moore. However, they provide little
      concerning what lessons their proposal has to offer developmental psychology more
      generally. I suggest three candidates and elaborate on how they raise outstanding
      methodological and philosophical questions for the approach taken in the target
      article.

PMID- 29342825
TI  - "What" matters more than "Why" - Neonatal behaviors initiate social responses.
AB  - Newborns are born into a social environment that dynamically responds to them.
      Newborn behaviors may not have explicit social intentions but will nonetheless
      affect the environment. Parents contingently respond to their child, enabling
      newborns to learn about the consequences of their behaviors and encouraging the
      behavior itself. Consequently, newborn behaviors may serve both biological and
      social-cognitive purposes during development.

PMID- 29342826
TI  - An unsettled debate: Key empirical and theoretical questions are still open.
AB  - Debates about neonatal imitation remain more open than Keven & Akins (K&A) imply.
      K&A do not recognize the primacy of the question concerning differential
      imitation and the links between experimental designs and more or less plausible
      theoretical assumptions. Moreover, they do not acknowledge previous theorizing on
      spontaneous behavior, the explanatory power of entrainment, and subtle
      connections with social cognition.

PMID- 29342827
TI  - Does early motor development contribute to speech perception?
AB  - At the end of the target article, Keven & Akins (K&A) put forward a challenge to
      the developmental psychology community to consider the development of complex
      psychological processes - in particular, intermodal infant perception - across
      different levels of analysis. We take up that challenge and consider the
      possibility that early emerging stereotypies might help explain the foundations
      of the link between speech perception and speech production.

PMID- 29342828
TI  - Turning the tide: A plea for cognitively lean interpretations of infant
      behaviour.
AB  - Keven & Akins (K&A) revisit the controversial subject of neonatal imitation
      through analysing the physiological foundations of neonatal spontaneous
      behaviour. Consequently, they regard imitative capacities in neonates as
      unlikely. We welcome this approach as an overdue encouragement to refuse
      cognitively rich interpretations as far as cognitively lean interpretations are
      conceivable, and apply this rationale to other phenomena in early childhood
      development.

PMID- 29342829
TI  - July 2017 Editor-in-Chief Letter.

PMID- 29342830
TI  - Methods to Improve Osseointegration of Dental Implants in Low Quality (Type-IV)
      Bone: An Overview.
AB  - Nowadays, dental implants have become more common treatment for replacing missing
      teeth and aim to improve chewing efficiency, physical health, and esthetics. The
      favorable clinical performance of dental implants has been attributed to their
      firm osseointegration, as introduced by Branemark in 1965. Although the survival
      rate of dental implants over a 10-year observation has been reported to be higher
      than 90% in totally edentulous jaws, the clinical outcome of implant treatment is
      challenged in compromised (bone) conditions, as are frequently present in elderly
      people. The biomechanical characteristics of bone in aged patients do not offer
      proper stability to implants, being similar to type-IV bone (Lekholm & Zarb
      classification), in which a decreased clinical fixation of implants has been
      clearly demonstrated. However, the search for improved osseointegration has
      continued forward for the new evolution of modern dental implants. This
      represents a continuum of developments spanning more than 20 years of research on
      implant related-factors including surgical techniques, implant design, and
      surface properties. The methods to enhance osseointegration of dental implants in
      low quality (type-IV) bone are described in a general manner in this review.

PMID- 29342831
TI  - Refugee Health: An Ongoing Commitment and Challenge.
AB  - Refugees represent a diverse group of displaced individuals with unique health
      issues and disease risks. The obstacles facing this population have their origins
      in war, violence, oppression, exploitation, and fear of persecution. Regardless
      of country of origin, a common bond exists, with refugees often confronting
      inadequate healthcare resources, xenophobia, discrimination, and a complex web of
      legal barriers in their new homelands. In many cases, the plight of refugees is
      multigenerational, manifesting as mental health issues, abuse, poverty, and
      family disruption. The health trajectory of refugees remains an ongoing
      commitment and challenge.

PMID- 29342832
TI  - Development of an Internal Real-Time Wireless Diagnostic Tool for a Proton
      Exchange Membrane Fuel Cell.
AB  - To prolong the operating time of unmanned aerial vehicles which use proton
      exchange membrane fuel cells (PEMFC), the performance of PEMFC is the key.
      However, a long-term operation can make the Pt particles of the catalyst layer
      and the pollutants in the feedstock gas bond together (e.g., CO), so that the
      catalyst loses reaction activity. The performance decay and aging of PEMFC will
      be influenced by operating conditions, temperature, flow and CO concentration.
      Therefore, this study proposes the development of an internal real-time wireless
      diagnostic tool for PEMFC, and uses micro-electro-mechanical systems (MEMS)
      technology to develop a wireless and thin (<50 MUm) flexible integrated
      (temperature, flow and CO) microsensor. The technical advantages are (1)
      compactness and three wireless measurement functions; (2) elastic measurement
      position and accurate embedding; (3) high accuracy and sensitivity and quick
      response; (4) real-time wireless monitoring of dynamic performance of PEMFC; (5)
      customized design and development. The flexible integrated microsensor is
      embedded in the PEMFC, three important physical quantities in the PEMFC, which
      are the temperature, flow and CO, can be measured simultaneously and instantly,
      so as to obtain the authentic and complete reaction in the PEMFC to enhance the
      performance of PEMFC and to prolong the service life.

PMID- 29342833
TI  - Structural Determination of Ruthenium Complexes Containing Bi-Dentate Pyrrole
      Ketone Ligands.
AB  - A series of ruthenium compounds containing a pyrrole-ketone bidentate ligand, 2
      (2'-methoxybenzoyl)pyrrole (1), have been synthesized and characterized. Reacting
      1 with [(eta6-cymene)RuCl2]2 and RuHCl(CO)(PPh3)3 generated Ru(eta6-cymene)[C4H3N
      2-(CO-C6H4-2-OMe)]Cl (2) and {RuCl(CO)(PPh3)2[C4H3N-2-(COC6H4-2-OMe)]} (3),
      respectively, in moderate yields. Successively reacting 2 with sodium cyanate and
      sodium azide gave {Ru(eta6-cymene)[C4H3N-2-(CO-C6H4-2-OMe)]X} (4, X=OCN; 5, X=N3)
      with the elimination of sodium chloride. Compounds 2-5 were all characterized by
      1H and 13C-NMR spectra and their structures were also determined by X-ray single
      crystallography.

PMID- 29342835
TI  - Small Peptides Able to Suppress Prostaglandin E2 Generation in Renal Mesangial
      Cells.
AB  - Peptide drug discovery may play a key role in the identification of novel
      medicinal agents. Here, we present the development of novel small peptides able
      to suppress the production of PGE2 in mesangial cells. The new compounds were
      generated by structural alterations applied on GK115, a novel inhibitor of
      secreted phospholipase A2, which has been previously shown to reduce PGE2
      synthesis in rat renal mesangial cells. Among the synthesized compounds, the
      tripeptide derivative 11 exhibited a nice dose-dependent suppression of PGE2
      production, similar to that observed for GK115.

PMID- 29342834
TI  - Facial Bone Reconstruction Using both Marine or Non-Marine Bone Substitutes:
      Evaluation of Current Outcomes in a Systematic Literature Review.
AB  - The aim of the present investigation was to systematically analyse the literature
      on the facial bone reconstruction defect using marine collagen or not and to
      evaluate a predictable treatment for their clinical management. The revision has
      been performed by searched MEDLINE and EMBASE databases from 2007 to 2017.
      Clinical trials and animal in vitro studies that had reported the application of
      bone substitutes or not for bone reconstruction defect and using marine collagen
      or other bone substitute material were recorded following Preferred Reporting
      Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The first
      selection involved 1201 citations. After screening and evaluation of suitability,
      39 articles were added at the revision process. Numerous discrepancies among the
      papers about bone defects morphology, surgical protocols, and selection of
      biomaterials were found. All selected manuscripts considered the final clinical
      success after the facial bone reconstruction applying bone substitutes. However,
      the scientific evidence regarding the vantage of the appliance of a biomaterial
      versus autologous bone still remains debated. Marine collagen seems to favor the
      dimensional stability of the graft and it could be an excellent carrier for
      growth factors.

PMID- 29342836
TI  - Cool-Climate Red Wines-Chemical Composition and Comparison of Two Protocols for
      1H-NMR Analysis.
AB  - This study investigates the metabolome of 26 experimental cool-climate wines made
      from 22 grape varieties using two different protocols for wine analysis by proton
      nuclear magnetic resonance (1H-NMR) spectroscopy. The wine samples were analyzed
      as-is (wet) and as dried samples. The NMR datasets were preprocessed by alignment
      and mean centering. No normalization or scaling was performed. The "wet" method
      preserved the inherent properties of the samples and provided a fast and
      effective overview of the molecular composition of the wines. The "dried" method
      yielded a slightly better sensitivity towards a broader range of the compounds
      present in wines. A total of 27 metabolites including amino acids, organic acids,
      sugars, and alkaloids were identified in the 1H-NMR spectra of the wine samples.
      Principal component analysis was performed on both NMR datasets evidencing well
      defined molecular fingerprints for 'Baco Noir', 'Bolero', 'Cabernet Cantor',
      'Cabernet Cortis', 'Don Muscat', 'Eszter', 'Golubok', 'New York Muscat',
      'Regent', 'Rondo', 'Triomphe d'Alsace', 'Precose Noir', and 'Vinoslivy' wines.
      Amongst the identified metabolites, lactic acid, succinic acid, acetic acid,
      gallic acid, glycerol, and methanol were found to drive sample groupings. The 1H
      NMR data was compared to the absolute concentration values obtained from a
      reference Fourier transform infrared method, evidencing a high correlation.

PMID- 29342837
TI  - Effect of Exposed Surface Area, Volume and Environmental pH on the Calcium Ion
      Release of Three Commercially Available Tricalcium Silicate Based Dental Cements.
AB  - Tricalcium silicate cements (TSC) are used in dental traumatology and endodontics
      for their bioactivity which is mostly attributed to formation of calcium
      hydroxide during TSC hydration and its subsequent release of calcium and
      hydroxide ions. The aim of this study was to determine the effect of volume
      (Vol), exposed surface area (ESA) and pH of surrounding medium on calcium ion
      release. Three commercially available hydraulic alkaline dental cements were
      mixed and condensed into cylindrical tubes of varying length and diameter (n =
      6/group). For the effect of ESA and Vol, tubes were immersed in 10 mL of
      deionized water. To analyze the effect of environmental pH, the tubes were
      randomly immersed in 10 mL of buffer solutions with varying pH (10.4, 7.4 or
      4.4). The solutions were collected and renewed at various time intervals. pH
      and/or calcium ion release was measured using a pH glass electrode and atomic
      absorption spectrophotometer respectively. The change of pH, short-term calcium
      ion release and rate at which calcium ion release reaches maximum were dependent
      on ESA (p < 0.05) while maximum calcium ion release was dependent on Vol of TSC
      (p < 0.05). Maximum calcium ion release was significantly higher in acidic
      solution followed by neutral and alkaline solution (p < 0.05).

PMID- 29342838
TI  - Biopolymer-Based Nanoparticles for Cystic Fibrosis Lung Gene Therapy Studies.
AB  - Lung gene therapy for cystic fibrosis disease has not been successful due to
      several challenges such as the absence of an appropriate vector. Therefore,
      optimal delivery of emerging therapeutics to airway epithelial cells demands
      suitable non-viral systems. In this work, we describe the formulation and the
      physicochemical investigation of biocompatible and biodegradable polymeric
      nanoparticles (NPs), including PLGA and chitosan (animal and non-animal), as
      novel methods for the safe and efficient delivery of CFTR-specific locked nucleic
      acids (LNAs).

PMID- 29342839
TI  - Calcium Phosphates as Delivery Systems for Bisphosphonates.
AB  - Bisphosphonates (BPs) are the most utilized drugs for the treatment of
      osteoporosis, and are usefully employed also for other pathologies characterized
      by abnormally high bone resorption, including bone metastases. Due to the great
      affinity of these drugs for calcium ions, calcium phosphates are ideal delivery
      systems for local administration of BPs to bone, which is aimed to avoid/limit
      the undesirable side effects of their prolonged systemic use. Direct synthesis in
      aqueous medium and chemisorptions from solution are the two main routes proposed
      to synthesize BP functionalized calcium phosphates. The present review overviews
      the information acquired through the studies on the interaction between
      bisphosphonate molecules and calcium phosphates. Moreover, particular attention
      is addressed to some important recent achievements on the applications of BP
      functionalized calcium phosphates as biomaterials for bone substitution/repair.

PMID- 29342840
TI  - Evaluation of Rapid, Early Warning Approaches to Track Shellfish Toxins
      Associated with Dinophysis and Alexandrium Blooms.
AB  - Marine biotoxin-contaminated seafood has caused thousands of poisonings worldwide
      this century. Given these threats, there is an increasing need for improved
      technologies that can be easily integrated into coastal monitoring programs. This
      study evaluates approaches for monitoring toxins associated with recurrent toxin
      producing Alexandrium and Dinophysis blooms on Long Island, NY, USA, which cause
      paralytic and diarrhetic shellfish poisoning (PSP and DSP), respectively. Within
      contrasting locations, the dynamics of pelagic Alexandrium and Dinophysis cell
      densities, toxins in plankton, and toxins in deployed blue mussels (Mytilus
      edulis) were compared with passive solid-phase adsorption toxin tracking (SPATT)
      samplers filled with two types of resin, HP20 and XAD-2. Multiple species of wild
      shellfish were also collected during Dinophysis blooms and used to compare toxin
      content using two different extraction techniques (single dispersive and double
      exhaustive) and two different toxin analysis assays (liquid chromatography/mass
      spectrometry and the protein phosphatase inhibition assay (PP2A)) for the
      measurement of DSP toxins. DSP toxins measured in the HP20 resin were
      significantly correlated (R2 = 0.7-0.9, p < 0.001) with total DSP toxins in
      shellfish, but were detected more than three weeks prior to detection in deployed
      mussels. Both resins adsorbed measurable levels of PSP toxins, but neither
      quantitatively tracked Alexandrium cell densities, toxicity in plankton or toxins
      in shellfish. DSP extraction and toxin analysis methods did not differ
      significantly (p > 0.05), were highly correlated (R2 = 0.98-0.99; p < 0.001) and
      provided complete recovery of DSP toxins from standard reference materials. Blue
      mussels (Mytilus edulis) and ribbed mussels (Geukensia demissa) were found to
      accumulate DSP toxins above federal and international standards (160 ng g-1)
      during Dinophysis blooms while Eastern oysters (Crassostrea virginica) and soft
      shell clams (Mya arenaria) did not. This study demonstrated that SPATT samplers
      using HP20 resin coupled with PP2A technology could be used to provide early
      warning of DSP, but not PSP, events for shellfish management.

PMID- 29342842
TI  - Investigating Effect of Service Encounter, Value, and Satisfaction on Word of
      Mouth: An Outpatient Service Context.
AB  - This study investigates the relationships among service encounter, service value,
      patient satisfaction, and word-of-mouth (WOM) intention from the viewpoint of
      interactive marketing. Data were collected using a questionnaire survey. A total
      of 372 questionnaires were obtained and 350 of these questionnaires were valid
      (94.09%), and a structural equation model was used to analyze the data. This
      study proposed seven hypotheses, and five of the seven hypotheses were supported.
      Service encounters indirectly affect their patient WOM through service value and
      satisfaction. Therefore, service value and satisfaction play a crucial mediating
      role in linking service encounters and WOM. This study determined WOM intentions
      in an outpatient service context and provides crucial business implications for
      teaching hospitals to enable them to improve their service quality and achieve a
      sustainable operation.

PMID- 29342841
TI  - miR-3189-3p Mimics Enhance the Effects of S100A4 siRNA on the Inhibition of
      Proliferation and Migration of Gastric Cancer Cells by Targeting CFL2.
AB  - GDF15 is a downstream gene of S100A4. miR-3189 is embedded in the intron of GDF15
      and coexpressed with it. miR-3189-3p functions to inhibit the proliferation and
      migration of glioblastoma cells. We speculated that S100A4 might regulate miR
      3189-3p to affect its function in gastric cancer cells. Quantitative reverse
      transcription polymerase chain reaction (qRT-PCR) showed that miR-3189-3p
      expression was significantly downregulated in MGC803 cells after S100A4
      knockdown. Overexpression of miR-3189-3p significantly inhibited the
      proliferation and migration of the cells. Moreover, miR-3189-3p mimics enhanced
      the effects of an S100A4 siRNA on the inhibition of cell proliferation and
      migration. Dual luciferase reporter assays, qRT-PCR, and Western blotting
      verified that CFL2 is a direct target of miR-3189-3p. CFL2 mediates the
      regulation of miR-3189-3p on the proliferation and migration of MGC803 cells.
      Data mining based on Kaplan-Meier plots showed that high CFL2 expression is
      associated with poor overall survival and first progression in gastric cancer.
      These data suggested that miR-3189-3p mimics enhanced the effects of the S100A4
      siRNA on the inhibition of gastric cancer cell proliferation and migration by
      targeting CFL2. The findings suggested that when targeting S100A4 to treat
      gastric cancer, consideration and correction for counteracting factors should
      obtain a satisfactory effect.

PMID- 29342843
TI  - Chiral and Molecular Recognition through Protonation between Aromatic Amino Acids
      and Tripeptides Probed by Collision-Activated Dissociation in the Gas Phase.
AB  - Chiral and molecular recognition through protonation was investigated through the
      collision-activated dissociation (CAD) of protonated noncovalent complexes of
      aromatic amino acid enantiomers with l-alanine- and l-serine-containing
      tripeptides using a linear ion trap mass spectrometer. In the case of l-alanine
      tripeptide (AAA), NH3 loss was observed in the CAD of heterochiral H+(d-Trp)AAA,
      while H2O loss was the main dissociation pathways for l-Trp, d-Phe, and l-Phe.
      The protonation site of heterochiral H+(d-Trp)AAA was the amino group of d-Trp,
      and the NH3 loss occurred from H+(d-Trp). The H2O loss indicated that the proton
      was attached to the l-alanine tripeptide in the noncovalent complexes. With the
      substitution of a central residue of l-alanine tripeptide to l-Ser, ASA
      recognized l-Phe by protonation to the amino group of l-Phe in homochiral H+(l
      Phe)ASA. For the protonated noncovalent complexes of His enantiomers with
      tripeptides (AAA, SAA, ASA, and AAS), protonated His was observed in the spectra,
      except for those of heterochiral H+(d-His)SAA and H+(d-His)AAS, indicating that d
      His did not accept protons from the SAA and AAS in the noncovalent complexes. The
      amino-acid sequences of the tripeptides required for the recognition of aromatic
      amino acids were determined by analyses of the CAD spectra.

PMID- 29342844
TI  - Short Vacation Improves Stress-Level and Well-Being in German-Speaking Middle
      Managers-A Randomized Controlled Trial.
AB  - Stress in the work place has a detrimental effect on people's health. Sufficient
      recovery is necessary to counteract severe chronic negative load reactions.
      Previous research has shown that vacationing for at least seven consecutive days
      provided an efficient recovery strategy. Yet, thus far, the effects of short
      vacations and the mode of vacation (whether at home or in a new environment) have
      rarely been studied. We investigated the immediate and long-term effects of a
      short vacation (four nights) on well-being and perceived stress and whether the
      mode of vacation impacted on these results. Data was obtained from 40 middle
      managers (67.5% men and 32.5% women). The intervention group (n = 20) spent a
      short vacation in a hotel outside their usual environment. The control group (n =
      20) spent their vacation at home. Results indicated that one single short-term
      vacation, independent of the mode, has large, positive and immediate effects on
      perceived stress, recovery, strain, and well-being. Strain levels decreased to a
      greater extent in the intervention group compared to the control group. The
      effects can still be detected at 30 days (recovery) and 45 days (well-being and
      strain) post-vacation. Encouraging middle management employees to take short
      vacations seems to be an efficient health promotion strategy; environmental
      effects seem to play a minor role.

PMID- 29342845
TI  - Anesthetic Preconditioning as Endogenous Neuroprotection in Glaucoma.
AB  - Blindness in glaucoma is the result of death of Retinal Ganglion Cells (RGCs) and
      their axons. RGC death is generally preceded by a stage of reversible dysfunction
      and structural remodeling. Current treatments aimed at reducing intraocular
      pressure (IOP) are ineffective or incompletely effective in management of the
      disease. IOP-independent neuroprotection or neuroprotection as adjuvant to IOP
      lowering in glaucoma remains a challenge as effective agents without side effects
      have not been identified yet. We show in DBA/2J mice with spontaneous IOP
      elevation and glaucoma that the lifespan of functional RGCs can be extended by
      preconditioning RGCs with retrobulbar lidocaine in one eye at four months of age
      that temporary blocks RGC axonal transport. The contralateral, PBS-injected eye
      served as control. Lidocaine-induced impairment of axonal transport to superior
      colliculi was assessed by intravitreal injection of cholera toxin B. Long-term
      (nine months) effect of lidocaine were assessed on RGC electrical responsiveness
      (PERG), IOP, expression of relevant protein (BDNF, TrkB, PSD95, GFAP,
      Synaptophysin, and GAPDH) and RGC density. While lidocaine treatment did not
      alter the age-related increase of IOP, TrkB expression was elevated, GFAP
      expression was decreased, RGC survival was improved by 35%, and PERG function was
      preserved. Results suggest that the lifespan of functional RGCs in mouse glaucoma
      can be extended by preconditioning RGCs in early stages of the disease using a
      minimally invasive treatment with retrobulbar lidocaine, a common ophthalmologic
      procedure. Lidocaine is inexpensive, safe and is approved by Food and Drug
      Administration (FDA) to be administered intravenously.

PMID- 29342846
TI  - Mental Health and Drivers of Need in Emergent and Non-Emergent Emergency
      Department (ED) Use: Do Living Location and Non-Emergent Care Sources Matter?
AB  - Emergency department (ED) utilization has increased due to factors such as
      admissions for mental health conditions, including suicide and self-harm. We
      investigate direct and moderating influences on non-emergent ED utilization
      through the Behavioral Model of Health Services Use. Through logistic regression,
      we examined correlates of ED use via 2014 New York State Department of Health
      Statewide Planning and Research Cooperative System outpatient data. Consistent
      with the primary hypothesis, mental health admissions were associated with
      emergent use across models, with only a slight decrease in effect size in rural
      living locations. Concerning moderating effects, Spanish/Hispanic origin was
      associated with increased likelihood for emergent ED use in the rural living
      location model, and non-emergent ED use for the no non-emergent source model.
      'Other' ethnic origin increased the likelihood of emergent ED use for rural
      living location and no non-emergent source models. The findings reveal 'need',
      including mental health admissions, as the largest driver for ED use. This may be
      due to mental healthcare access, or patients with mental health emergencies being
      transported via first responders to the ED, as in the case of suicide, self-harm,
      manic episodes or psychotic episodes. Further educating ED staff on this patient
      population through gatekeeper training may ensure patients receive the best
      treatment and aid in driving access to mental healthcare delivery changes.

PMID- 29342847
TI  - How Work Characteristics Are Related to European Workers' Psychological Well
      Being. A Comparison of Two Age Groups.
AB  - This study aimed to analyze the mechanisms through which work characteristics are
      related to psychological well-being, exploring the mediational role of work
      meaningfulness and job satisfaction, and investigating differences in the
      patterns of relationships between two age groups. The sample was composed of
      36,896 workers from the 5th European Working Conditions Survey. Structural
      equation modeling analyses and multiple group analyses were performed. The
      results revealed a parallel mediational model, in which work meaningfulness and
      general job satisfaction mediate the relationships between work characteristics
      and well-being. Additionally, job satisfaction partially mediates the
      relationship between meaningfulness and well-being. These results were confirmed
      in both age groups (under 55 years old and older workers), but age moderates the
      relationships between social support and the mediating variables and the
      relationships between the mediating variables and general well-being. The present
      study uncovers significant pathways through which time pressure, decision
      latitude, and social support are related to psychological well-being, depicting
      an important step in better understanding how and when work characteristics are
      related to positive outcomes. It provides important clues for promoting
      psychosocial health at work at the European level.

PMID- 29342848
TI  - A Voltammetric Electronic Tongue for the Resolution of Ternary Nitrophenol
      Mixtures.
AB  - This work reports the applicability of a voltammetric sensor array able to
      quantify the content of 2,4-dinitrophenol, 4-nitrophenol, and picric acid in
      artificial samples using the electronic tongue (ET) principles. The ET is based
      on cyclic voltammetry signals, obtained from an array of metal disk electrodes
      and a graphite epoxy composite electrode, compressed using discrete wavelet
      transform with chemometric tools such as artificial neural networks (ANNs). ANNs
      were employed to build the quantitative prediction model. In this manner, a set
      of standards based on a full factorial design, ranging from 0 to 300 mg.L-1, was
      prepared to build the model; afterward, the model was validated with a completely
      independent set of standards. The model successfully predicted the concentration
      of the three considered phenols with a normalized root mean square error of 0.030
      and 0.076 for the training and test subsets, respectively, and r >= 0.948.

PMID- 29342849
TI  - Comparative Response of the Hepatic Transcriptomes of Domesticated and Wild
      Turkey to Aflatoxin B1.
AB  - The food-borne mycotoxin aflatoxin B1 (AFB1) poses a significant risk to poultry,
      which are highly susceptible to its hepatotoxic effects. Domesticated turkeys
      (Meleagris gallopavo) are especially sensitive, whereas wild turkeys (M. g.
      silvestris) are more resistant. AFB1 toxicity entails bioactivation by hepatic
      cytochrome P450s to the electrophilic exo-AFB1-8,9-epoxide (AFBO). Domesticated
      turkeys lack functional hepatic GST-mediated detoxification of AFBO, and this is
      largely responsible for the differences in resistance between turkey types. This
      study was designed to characterize transcriptional changes induced in turkey
      livers by AFB1, and to contrast the response of domesticated (susceptible) and
      wild (more resistant) birds. Gene expression responses to AFB1 were examined
      using RNA-sequencing. Statistically significant differences in gene expression
      were observed among treatment groups and between turkey types. Expression
      analysis identified 4621 genes with significant differential expression (DE) in
      AFB1-treated birds compared to controls. Characterization of DE transcripts
      revealed genes dis-regulated in response to toxic insult with significant
      association of Phase I and Phase II genes and others important in cellular
      regulation, modulation of apoptosis, and inflammatory responses. Constitutive
      expression of GSTA3 was significantly higher in wild birds and was significantly
      higher in AFB1-treated birds when compared to controls for both genetic groups.
      This pattern was also observed by qRT-PCR in other wild and domesticated turkey
      strains. Results of this study emphasize the differential response of these
      genetically distinct birds, and identify genes and pathways that are
      differentially altered in aflatoxicosis.

PMID- 29342850
TI  - Multi-Sensor Based Online Attitude Estimation and Stability Measurement of
      Articulated Heavy Vehicles.
AB  - Articulated wheel loaders used in the construction industry are heavy vehicles
      and have poor stability and a high rate of accidents because of the unpredictable
      changes of their body posture, mass and centroid position in complex operation
      environments. This paper presents a novel distributed multi-sensor system for
      real-time attitude estimation and stability measurement of articulated wheel
      loaders to improve their safety and stability. Four attitude and heading
      reference systems (AHRS) are constructed using micro-electro-mechanical system
      (MEMS) sensors, and installed on the front body, rear body, rear axis and boom of
      an articulated wheel loader to detect its attitude. A complementary filtering
      algorithm is deployed for sensor data fusion in the system so that steady state
      margin angle (SSMA) can be measured in real time and used as the judge index of
      rollover stability. Experiments are conducted on a prototype wheel loader, and
      results show that the proposed multi-sensor system is able to detect potential
      unstable states of an articulated wheel loader in real-time and with high
      accuracy.

PMID- 29342851
TI  - Laser Machining and In Vitro Assessment of Wollastonite-Tricalcium Phosphate
      Eutectic Glasses and Glass-Ceramics.
AB  - Bioactivity and ingrowth of ceramic implants is commonly enhanced by a suitable
      interconnected porous network. In this work, the laser machining of CaSiO3
      Ca3(PO4)2 biocompatible eutectic glass-ceramics and glasses was studied. For this
      purpose, 300 um diameter craters were machined by using pulsed laser radiation at
      532 nm with a pulsewidth in the nanosecond range. Machined samples were soaked in
      simulated body fluid for 2 months to assess the formation of a hydroxyapatite
      layer on the surface of the laser machined areas. The samples were manufactured
      by the laser floating zone technique using a CO2 laser. Morphology, composition
      and microstructure of the machined samples were described by Field Emission
      Scanning Electron Microscopy, Energy Dispersive X-ray Spectroscopy and micro
      Raman Spectroscopy.

PMID- 29342852
TI  - Atmospheric Environment Vulnerability Cause Analysis for the Beijing-Tianjin
      Hebei Metropolitan Region.
AB  - Assessing and quantifying atmospheric vulnerability is a key issue in urban
      environmental protection and management. This paper integrated the Analytical
      hierarchy process (AHP), fuzzy synthesis evaluation and Geographic Information
      System (GIS) spatial analysis into an Exposure-Sensitivity-Adaptive capacity
      (ESA) framework to quantitatively assess atmospheric environment vulnerability in
      the Beijing-Tianjin-Hebei (BTH) region with spatial and temporal comparisons. The
      elaboration of the relationships between atmospheric environment vulnerability
      and indices of exposure, sensitivity, and adaptive capacity supports enable
      analysis of the atmospheric environment vulnerability. Our findings indicate that
      the atmospheric environment vulnerability of 13 cities in the BTH region exhibits
      obvious spatial heterogeneity, which is caused by regional diversity in exposure,
      sensitivity, and adaptive capacity indices. The results of atmospheric
      environment vulnerability assessment and the cause analysis can provide guidance
      to pick out key control regions and recognize vulnerable indicators for study
      sites. The framework developed in this paper can also be replicated at different
      spatial and temporal scales using context-specific datasets to support
      environmental management.

PMID- 29342853
TI  - Structural Examination of Halogen-Bonded Co-Crystals of Tritopic Acceptors.
AB  - A series of tritopic N-heterocyclic compounds containing electrostatically and
      geometrically equivalent binding sites were synthesized and subjected to
      systematic co-crystallizations with selected perfluoroiodoarenes in order to map
      out their structural landscapes. More than 70% of the attempted reactions
      produced a co-crystal as indicated by IR spectroscopy. Four new crystal
      structures are reported and in all of them, at least one potential binding site
      on the acceptor is left vacant. The absence of halogen bonds to all sites can be
      ascribed primarily due to deactivation of the sigma-hole on the iodo-arene donors
      and partially due to steric hindrance. The tritopic acceptors containing 5,6
      dimethylbenzimidazole derivatives yield discrete tetrameric aggregates in the
      solid state, whereas the pyrazole and imidazole analogues assemble into halogen
      bonded 1-D chains.

PMID- 29342854
TI  - Impact of Prolonged Blood Incubation and Extended Serum Storage at Room
      Temperature on the Human Serum Metabolome.
AB  - Metabolomics is a powerful technology with broad applications in life science
      that, like other -omics approaches, requires high-quality samples to achieve
      reliable results and ensure reproducibility. Therefore, along with quality
      assurance, methods to assess sample quality regarding pre-analytical confounders
      are urgently needed. In this study, we analyzed the response of the human serum
      metabolome to pre-analytical variations comprising prolonged blood incubation and
      extended serum storage at room temperature by using gas chromatography-mass
      spectrometry (GC-MS) and liquid chromatography-tandem mass spectrometry (LC
      MS/MS) -based metabolomics. We found that the prolonged incubation of blood
      results in a statistically significant 20% increase and 4% decrease of 225 tested
      serum metabolites. Extended serum storage affected 21% of the analyzed
      metabolites (14% increased, 7% decreased). Amino acids and nucleobases showed the
      highest percentage of changed metabolites in both confounding conditions, whereas
      lipids were remarkably stable. Interestingly, the amounts of taurine and O
      phosphoethanolamine, which have both been discussed as biomarkers for various
      diseases, were 1.8- and 2.9-fold increased after 6 h of blood incubation. Since
      we found that both are more stable in ethylenediaminetetraacetic acid (EDTA)
      blood, EDTA plasma should be the preferred metabolomics matrix.

PMID- 29342855
TI  - Introduction to State Estimation of High-Rate System Dynamics.
AB  - Engineering systems experiencing high-rate dynamic events, including airbags,
      debris detection, and active blast protection systems, could benefit from real
      time observability for enhanced performance. However, the task of high-rate state
      estimation is challenging, in particular for real-time applications where the
      rate of the observer's convergence needs to be in the microsecond range. This
      paper identifies the challenges of state estimation of high-rate systems and
      discusses the fundamental characteristics of high-rate systems. A survey of
      applications and methods for estimators that have the potential to produce
      accurate estimations for a complex system experiencing highly dynamic events is
      presented. It is argued that adaptive observers are important to this research.
      In particular, adaptive data-driven observers are advantageous due to their
      adaptability and lack of dependence on the system model.

PMID- 29342856
TI  - Calculation and Identification of the Aerodynamic Parameters for Small-Scaled
      Fixed-Wing UAVs.
AB  - The establishment of the Aircraft Dynamic Model(ADM) constitutes the prerequisite
      for the design of the navigation and control system, but the aerodynamic
      parameters in the model could not be readily obtained especially for small-scaled
      fixed-wing UAVs. In this paper, the procedure of computing the aerodynamic
      parameters is developed. All the longitudinal and lateral aerodynamic derivatives
      are firstly calculated through semi-empirical method based on the aerodynamics,
      rather than the wind tunnel tests or fluid dynamics software analysis. Secondly,
      the residuals of each derivative are proposed to be identified or estimated
      further via Extended Kalman Filter(EKF), with the observations of the attitude
      and velocity from the airborne integrated navigation system. Meanwhile, the
      observability of the targeted parameters is analyzed and strengthened through
      multiple maneuvers. Based on a small-scaled fixed-wing aircraft driven by
      propeller, the airborne sensors are chosen and the model of the actuators are
      constructed. Then, real flight tests are implemented to verify the calculation
      and identification process. Test results tell the rationality of the semi
      empirical method and show the improvement of accuracy of ADM after the
      compensation of the parameters.

PMID- 29342857
TI  - An Adaptive Deghosting Method in Neural Network-Based Infrared Detectors
      Nonuniformity Correction.
AB  - The problems of the neural network-based nonuniformity correction algorithm for
      infrared focal plane arrays mainly concern slow convergence speed and ghosting
      artifacts. In general, the more stringent the inhibition of ghosting, the slower
      the convergence speed. The factors that affect these two problems are the
      estimated desired image and the learning rate. In this paper, we propose a
      learning rate rule that combines adaptive threshold edge detection and a temporal
      gate. Through the noise estimation algorithm, the adaptive spatial threshold is
      related to the residual nonuniformity noise in the corrected image. The proposed
      learning rate is used to effectively and stably suppress ghosting artifacts
      without slowing down the convergence speed. The performance of the proposed
      technique was thoroughly studied with infrared image sequences with both
      simulated nonuniformity and real nonuniformity. The results show that the
      deghosting performance of the proposed method is superior to that of other neural
      network-based nonuniformity correction algorithms and that the convergence speed
      is equivalent to the tested deghosting methods.

PMID- 29342858
TI  - Novel Fiber-Optic Ring Acoustic Emission Sensor.
AB  - Acoustic emission technology has been applied to many fields for many years.
      However, the conventional piezoelectric acoustic emission sensors cannot be used
      in extreme environments, such as those with heavy electromagnetic interference,
      high pressure, or strong corrosion. In this paper, a novel fiber-optic ring
      acoustic emission sensor is proposed. The sensor exhibits high sensitivity, anti
      electromagnetic interference, and corrosion resistance. First, the principle of a
      novel fiber-optic ring sensor is introduced. Different from piezoelectric and
      other fiber acoustic emission sensors, this novel sensor includes both a sensing
      skeleton and a sensing fiber. Second, a heterodyne interferometric demodulating
      method is presented. In addition, a fiber-optic ring sensor acoustic emission
      system is built based on this method. Finally, fiber-optic ring acoustic emission
      experiments are performed. The novel fiber-optic ring sensor is glued onto the
      surface of an aluminum plate. The 150 kHz standard continuous sinusoidal signals
      and broken lead signals are successfully detected by the novel fiber-optic ring
      acoustic emission sensor. In addition, comparison to the piezoelectric acoustic
      emission sensor is performed, which shows the availability and reliability of the
      novel fiber-optic ring acoustic emission sensor. In the future, this novel fiber
      optic ring acoustic emission sensor will provide a new route to acoustic emission
      detection in harsh environments.

PMID- 29342859
TI  - Multinuclear NMR Measurements and DFT Calculations for Capecitabine Tautomeric
      Form Assignment in a Solution.
AB  - The molecular structure of capecitabine (a widely applied prodrug of 5
      fluorouracil) was studied by multinuclear NMR measurements and DFT quantum
      mechanical calculations. One or two tautomeric forms in a solution were detected
      depending on the solvent used. In the organic solvents, a mixture of two forms of
      capecitabine was observed: carbamate and imine tautomers. In the aqueous
      solution, only the carbamate form was found. The methylation of capecitabine
      yields mainly two products in different proportions: N3-methylcapecitabine and N7
      methylcapecitabine. The protonation of capecitabine in organic solvents with
      perchloric acid occurs at the N3 nitrogen atom. DFT calculations strongly support
      the results coming from the analysis of the NMR spectra.

PMID- 29342860
TI  - AuNPs Hybrid Black ZnO Nanorods Made by a Sol-Gel Method for Highly Sensitive
      Humidity Sensing.
AB  - A highly sensitive self-powered humidity sensor has been realized from AuNPs
      hybrid black zinc oxide (ZnO) nanorods prepared through a sol-gel method. XRD
      pattern reveals that both ZnO and ZnO/AuNPs exhibit a wurtzite structure.
      ZnO/AuNPs nanorods grow in a vertical alignment, which possesses high uniformity
      and forms dense arrays with a smaller diameter than that of ZnO nanoparticles.
      All ZnO/AuNPs and pure black ZnO show lower band gap energy than the typically
      reported 3.34 eV of pure ZnO. Furthermore, the band gap of ZnO/AuNPs
      nanocomposites is effectively influenced by the amount of AuNPs. The humidity
      sensing tests clearly prove that all the ZnO/AuNPs humidity sensors exhibit much
      higher response than that of ZnO sensors, and the sensitivity of such ZnO/AuNPs
      nanorods (6 mL AuNPs) display a change three orders higher than that of pure ZnO
      with relative humidity (RH) ranging from 11% to 95% at room temperature. The
      response and recovery time of the ZnO/AuNPs are 5.6 s and 32.4 s, respectively.
      This study of the construction of semiconductor/noble metal sensors provides a
      rational way to control the morphology of semiconductor nanomaterials and to
      design a humidity sensor with high performance.

PMID- 29342862
TI  - Heterogeneous Contributing Factors in MPM Disease Development and Progression:
      Biological Advances and Clinical Implications.
AB  - Malignant pleural mesothelioma (MPM) tumors are remarkably aggressive and most
      patients only survive for 5-12 months; irrespective of stage; after primary
      symptoms appear. Compounding matters is that MPM remains unresponsive to
      conventional standards of care; including radiation and chemotherapy. Currently;
      instead of relying on molecular signatures and histological typing; MPM treatment
      options are guided by clinical stage and patient characteristics because the
      mechanism of carcinogenesis has not been fully elucidated; although about 80% of
      cases can be linked to asbestos exposure. Several molecular pathways have been
      implicated in the MPM tumor microenvironment; such as angiogenesis; apoptosis;
      cell-cycle regulation and several growth factor-related pathways predicted to be
      amenable to therapeutic intervention. Furthermore, the availability of genomic
      data has improved our understanding of the pathobiology of MPM. The MPM genomic
      landscape is dominated by inactivating mutations in several tumor suppressor
      genes; such as CDKN2A; BAP1 and NF2. Given the complex heterogeneity of the tumor
      microenvironment in MPM; a better understanding of the interplay between stromal;
      endothelial and immune cells at the molecular level is required; to chaperone the
      development of improved personalized therapeutics. Many recent advances at the
      molecular level have been reported and several exciting new treatment options are
      under investigation. Here; we review the challenges and the most up-to-date
      biological advances in MPM pertaining to the molecular pathways implicated;
      progress at the genomic level; immunological progression of this fatal disease;
      and its link with developmental cell pathways; with an emphasis on prognostic and
      therapeutic treatment strategies.

PMID- 29342863
TI  - Validation of a Rapid Method to Assess Habitual Beverage Intake Patterns.
AB  - The Healthy Beverage Index (HBI) is an emerging approach to assess beverage
      pattern quality. HBI total scores range from 0 to 100, with higher scores
      indicating greater adherence to proposed beverage recommendations. However,
      assessing patterns is resource-intensive due to the need for extensive dietary
      data, typically 24-h dietary records or recalls. The BEVQ-15, a beverage intake
      questionnaire, may be used as an alternative method to rapidly measure HBI
      scores. The objective of this cross-sectional investigation is to assess the
      comparative validity of the HBI-Q, a method to rapidly assess HBI scores via the
      BEVQ-15, as compared to the traditional method of deriving HBI scores via dietary
      recalls/records. Between 2012 and 2016, a cross-sectional sample of adults in
      southwest Virginia completed three 24-h dietary recalls (30-60 min administration
      and analysis time per recall) and the BEVQ-15 (3-4 min administration time). HBI
      scores were generated by both methods, and compared via paired-samples t-tests,
      correlations, and Bland-Altman analysis. Among 404 adults (mean age = 40 years),
      total mean HBI scores were 63.7 from the HBI-Q and 67.3 from the recalls (mean
      difference = 3.6 out of 100; r = 0.63; both p <= 0.001). Agreement between the
      two methods for total HBI scores via Bland-Altman plots was 92%. Using the HBI-Q
      to rapidly assess HBI scores in adults will increase the utility of the HBI by
      decreasing the time and resources required, thus allowing researchers and
      practitioners to provide targeted feedback for improvement.

PMID- 29342861
TI  - Rational Management of Iron-Deficiency Anaemia in Inflammatory Bowel Disease.
AB  - Anaemia is the most frequent, though often neglected, comorbidity of inflammatory
      bowel disease (IBD). Here we want to briefly present (1) the burden of anaemia in
      IBD, (2) its pathophysiology, which mostly arises from bleeding-associated iron
      deficiency, followed by (3) diagnostic evaluation of anaemia, (4) a balanced
      overview of the different modes of iron replacement therapy, (5) evidence for
      their therapeutic efficacy and subsequently, (6) an updated recommendation for
      the practical management of anaemia in IBD. Following the introduction of various
      intravenous iron preparations over the last decade, questions persist about when
      to use these preparations as opposed to traditional and other novel oral iron
      therapeutic agents. At present, oral iron therapy is generally preferred for
      patients with quiescent IBD and mild iron-deficiency anaemia. However, in
      patients with flaring IBD that hampers intestinal iron absorption and in those
      with inadequate responses to or side effects with oral preparations, intravenous
      iron supplementation is the therapy of choice, although information on the
      efficacy of intravenous iron in patients with active IBD and anaemia is scare.
      Importantly, anaemia in IBD is often multifactorial and a careful diagnostic
      workup is mandatory for optimized treatment. Nevertheless, limited information is
      available on optimal therapeutic start and end points for treatment of anaemia.
      Of note, neither oral nor intravenous therapies seem to exacerbate the clinical
      course of IBD. However, additional prospective studies are still warranted to
      determine the optimal therapy in complex conditions such as IBD.

PMID- 29342864
TI  - Mechanical Properties of a Newly Additive Manufactured Implant Material Based on
      Ti-42Nb.
AB  - The application of Ti-6Al-4V alloy or commercially pure titanium for additive
      manufacturing enables the fabrication of complex structural implants and patient
      specific implant geometries. However, the difference in Young's modulus of alpha
      + beta-phase Ti alloys compared to the human bone promotes stress-shielding
      effects in the implant-bone interphase. The aim of the present study is the
      mechanical characterization of a new pre-alloyed beta-phase Ti-42Nb alloy for
      application in additive manufacturing. The present investigation focuses on the
      mechanical properties of SLM-printed Ti-42Nb alloy in tensile and compression
      tests. In addition, the raw Ti-42Nb powder, the microstructure of the specimens
      prior to and after compression tests, as well as the fracture occurring in
      tensile tests are characterized by means of the SEM/EDX analysis. The Ti-42Nb raw
      powder exhibits a dendrite-like Ti-structure, which is melted layer-by-layer into
      a microstructure with a very homogeneous distribution of Nb and Ti during the SLM
      process. Tensile tests display Young's modulus of 60.51 +/- 3.92 GPa and an
      ultimate tensile strength of 683.17 +/- 16.67 MPa, whereas, under a compressive
      load, a compressive strength of 1330.74 +/- 53.45 MPa is observed. The
      combination of high mechanical strength and low elastic modulus makes Ti-42Nb an
      interesting material for orthopedic and dental implants. The spherical shape of
      the pre-alloyed material additionally allows for application in metal 3D
      printing, enabling the fabrication of patient-specific structural implants.

PMID- 29342865
TI  - Acute Post-Prandial Cognitive Effects of Brown Seaweed Extract in Humans.
AB  - (Poly)phenols and, specifically, phlorotannins present in brown seaweeds have
      previously been shown to inhibit alpha-amylase and alpha-glucosidase, key enzymes
      involved in the breakdown and intestinal absorption of carbohydrates. Related to
      this are observations of modulation of post-prandial glycemic response in mice
      and increased insulin sensitivity in humans when supplemented with seaweed
      extract. However, no studies to date have explored the effect of seaweed extract
      on cognition. The current randomized, placebo-controlled, double-blind, parallel
      groups study examined the impact of a brown seaweed extract on cognitive function
      post-prandially in 60 healthy adults (N = 30 per group). Computerized measures of
      episodic memory, attention and subjective state were completed at baseline and 5
      times at 40 min intervals over a 3 h period following lunch, with either seaweed
      or placebo consumed 30 min prior to lunch. Analysis was conducted with linear
      mixed models controlling for baseline. Seaweed led to significant improvements to
      accuracy on digit vigilance (p = 0.035) and choice reaction time (p = 0.043)
      tasks. These findings provide the first evidence for modulation of cognition with
      seaweed extract. In order to explore the mechanism underlying these effects,
      future research should examine effects on cognition in parallel with blood
      glucose and insulin responses.

PMID- 29342866
TI  - Guanidinoacetic Acid and Creatine are Associated with Cardiometabolic Risk
      Factors in Healthy Men and Women: A Cross-Sectional Study.
AB  - Guanidinoacetic acid (GAA) conversion to creatine is thought to be involved in
      cardiometabolic disturbances through its role in biological methylation and
      insulin secretion. We evaluated the association of serum GAA and creatine with
      cardiometabolic risk factors in a cohort of 151 apparently healthy adults (82
      women and 69 men) aged 18-63 years. Serum levels of GAA and creatine were
      measured with liquid chromatography-tandem mass spectrometry. A multiple linear
      regression model adjusted for age and sex was employed to examine the
      relationship of serum GAA and creatine with cardiometabolic risk factors. Higher
      GAA levels were associated with an unfavorable cardiometabolic risk profile
      (higher insulin, higher total homocysteine, and higher body fat percentage),
      while having elevated serum creatine levels (>=31.1 umol/L) was associated with
      being overweight (body mass index >= 25.0 kg/m). The results from our study
      suggest a possible role of the GAA-creatine axis in the pathogenesis of
      cardiovascular and metabolic diseases.

PMID- 29342867
TI  - A Longitudinal Study of 25-Hydroxy Vitamin D and Parathyroid Hormone Status
      throughout Pregnancy and Exclusive Lactation in New Zealand Mothers and Their
      Infants at 45 degrees  S.
AB  - Vitamin D status and associated metabolism during pregnancy and lactation have
      been assessed in only a limited number of longitudinal studies, all from the
      northern hemisphere, with no infant data concurrently reported. Therefore, we
      aimed to describe longitudinal maternal and infant 25-hydroxy vitamin D (25OHD)
      and parathyroid hormone (PTH) status during pregnancy and up to 5 months
      postnatal age, in New Zealand women and their infants living at 45 degrees  S
      latitude. Between September 2011 and June 2013, 126 pregnant women intending to
      exclusively breastfeed for at least 20 weeks were recruited. Longitudinal data
      were collected at three time-points spanning pregnancy, and following birth and
      at 20 weeks postpartum. Vitamin D deficiency (25OHD < 50 nmol/L) was common,
      found at one or more time-points in 65% and 76% of mothers and their infants,
      respectively. Mean cord 25OHD was 41 nmol/L, and three infants exhibited
      secondary hyperparathyroidism by postnatal week 20. Maternal late pregnancy 25OHD
      (gestation 32-38 weeks) was closely correlated with infant cord 25OHD, r2 = 0.87
      (95% CI (Confidence interval) 0.8-0.91), while no correlation was seen between
      early pregnancy (<20 weeks gestation) maternal and cord 25OHD, r2 = 0.06 (95% CI 
      0.16-0.28). Among other variables, pregnancy 25OHD status, and therefore infant
      status at birth, were influenced by season of conception. In conclusion, vitamin
      D deficiency in women and their infants is very common during pregnancy and
      lactation in New Zealand at 45 degrees  S. These data raise questions regarding
      the applicability of current pregnancy and lactation policy at this latitude,
      particularly recommendations relating to first trimester maternal vitamin D
      screening and targeted supplementation for those "at risk".

PMID- 29342869
TI  - Surface Fitting for Quasi Scattered Data from Coordinate Measuring Systems.
AB  - Non-uniform rational B-spline (NURBS) surface fitting from data points is wildly
      used in the fields of computer aided design (CAD), medical imaging, cultural
      relic representation and object-shape detection. Usually, the measured data
      acquired from coordinate measuring systems is neither gridded nor completely
      scattered. The distribution of this kind of data is scattered in physical space,
      but the data points are stored in a way consistent with the order of measurement,
      so it is named quasi scattered data in this paper. Therefore they can be
      organized into rows easily but the number of points in each row is random. In
      order to overcome the difficulty of surface fitting from this kind of data, a new
      method based on resampling is proposed. It consists of three major steps: (1)
      NURBS curve fitting for each row, (2) resampling on the fitted curve and (3)
      surface fitting from the resampled data. Iterative projection optimization scheme
      is applied in the first and third step to yield advisable parameterization and
      reduce the time cost of projection. A resampling approach based on parameters,
      local peaks and contour curvature is proposed to overcome the problems of nodes
      redundancy and high time consumption in the fitting of this kind of scattered
      data. Numerical experiments are conducted with both simulation and practical
      data, and the results show that the proposed method is fast, effective and
      robust. What's more, by analyzing the fitting results acquired form data with
      different degrees of scatterness it can be demonstrated that the error introduced
      by resampling is negligible and therefore it is feasible.

PMID- 29342868
TI  - Hypoxia and Hormone-Mediated Pathways Converge at the Histone Demethylase KDM4B
      in Cancer.
AB  - Hormones play an important role in pathophysiology. The hormone receptors, such
      as estrogen receptor alpha and androgen receptor in breast cancer and prostate
      cancer, are critical to cancer cell proliferation and tumor growth. In this
      review we focused on the cross-talk between hormone and hypoxia pathways,
      particularly in breast cancer. We delineated a novel signaling pathway from
      estrogen receptor to hypoxia-inducible factor 1, and discussed the role of this
      pathway in endocrine therapy resistance. Further, we discussed the estrogen and
      hypoxia pathways converging at histone demethylase KDM4B, an important epigenetic
      modifier in cancer.

PMID- 29342870
TI  - Biomarkers of Progression after HIV Acute/Early Infection: Nothing Compares to
      CD4+ T-cell Count?
AB  - Progression of HIV infection is variable among individuals, and definition
      disease progression biomarkers is still needed. Here, we aimed to categorize the
      predictive potential of several variables using feature selection methods and
      decision trees. A total of seventy-five treatment-naive subjects were enrolled
      during acute/early HIV infection. CD4+ T-cell counts (CD4TC) and viral load (VL)
      levels were determined at enrollment and for one year. Immune activation, HIV
      specific immune response, Human Leukocyte Antigen (HLA) and C-C chemokine
      receptor type 5 (CCR5) genotypes, and plasma levels of 39 cytokines were
      determined. Data were analyzed by machine learning and non-parametric methods.
      Variable hierarchization was performed by Weka correlation-based feature
      selection and J48 decision tree. Plasma interleukin (IL)-10, interferon gamma
      induced protein (IP)-10, soluble IL-2 receptor alpha (sIL-2Ralpha) and tumor
      necrosis factor alpha (TNF-alpha) levels correlated directly with baseline VL,
      whereas IL-2, TNF-alpha, fibroblast growth factor (FGF)-2 and macrophage
      inflammatory protein (MIP)-1beta correlated directly with CD4+ T-cell activation
      (p < 0.05). However, none of these cytokines had good predictive values to
      distinguish "progressors" from "non-progressors". Similarly, immune activation,
      HIV-specific immune responses and HLA/CCR5 genotypes had low discrimination
      power. Baseline CD4TC was the most potent discerning variable with a cut-off of
      438 cells/MUL (accuracy = 0.93, kappa-Cohen = 0.85). Limited discerning power of
      the other factors might be related to frequency, variability and/or sampling
      time. Future studies based on decision trees to identify biomarkers of post
      treatment control are warrantied.

PMID- 29342872
TI  - Human Cytomegalovirus Nuclear Capsids Associate with the Core Nuclear Egress
      Complex and the Viral Protein Kinase pUL97.
AB  - The nuclear phase of herpesvirus replication is regulated through the formation
      of regulatory multi-component protein complexes. Viral genomic replication is
      followed by nuclear capsid assembly, DNA encapsidation and nuclear egress. The
      latter has been studied intensely pointing to the formation of a viral core
      nuclear egress complex (NEC) that recruits a multimeric assembly of viral and
      cellular factors for the reorganization of the nuclear envelope. To date, the
      mechanism of the association of human cytomegalovirus (HCMV) capsids with the
      NEC, which in turn initiates the specific steps of nuclear capsid budding,
      remains undefined. Here, we provide electron microscopy-based data demonstrating
      the association of both nuclear capsids and NEC proteins at nuclear lamina
      budding sites. Specifically, immunogold labelling of the core NEC constituent
      pUL53 and NEC-associated viral kinase pUL97 suggested an intranuclear NEC-capsid
      interaction. Staining patterns with phospho-specific lamin A/C antibodies are
      compatible with earlier postulates of targeted capsid egress at lamina-depleted
      areas. Important data were provided by co-immunoprecipitation and in vitro kinase
      analyses using lysates from HCMV-infected cells, nuclear fractions, or infectious
      virions. Data strongly suggest that nuclear capsids interact with pUL53 and
      pUL97. Combined, the findings support a refined concept of HCMV nuclear
      trafficking and NEC-capsid interaction.

PMID- 29342871
TI  - Interferons: Reprogramming the Metabolic Network against Viral Infection.
AB  - Viruses exploit the host and induce drastic metabolic changes to ensure an
      optimal environment for replication and the production of viral progenies. In
      response, the host has developed diverse countermeasures to sense and limit these
      alterations to combat viral infection. One such host mechanism is through
      interferon signaling. Interferons are cytokines that enhances the transcription
      of hundreds of interferon-stimulated genes (ISGs) whose products are key players
      in the innate immune response to viral infection. In addition to their direct
      targeting of viral components, interferons and ISGs exert profound effects on
      cellular metabolism. Recent studies have started to illuminate on the specific
      role of interferon in rewiring cellular metabolism to activate immune cells and
      limit viral infection. This review reflects on our current understanding of the
      complex networking that occurs between the virus and host at the interface of
      cellular metabolism, with a focus on the ISGs in particular, cholesterol-25
      hydroxylase (CH25H), spermidine/spermine acetyltransferase 1 (SAT1), indoleamine
      2,3-dioxygenase (IDO1) and sterile alpha motif and histidine/aspartic acid domain
      containing protein 1 (SAMHD1), which were recently discovered to modulate
      specific metabolic events and consequently deter viral infection.

PMID- 29342873
TI  - Association between the Frequency of Protein-Rich Food Intakes and Kihon
      Checklist Frailty Indices in Older Japanese Adults: The Kyoto-Kameoka Study.
AB  - We aimed to investigate whether frequencies of protein-rich food intake were
      associated with frailty among older Japanese adults. A cross-sectional study was
      conducted in 2011 among 3843 men and 4331 women in a population-based cohort of
      Kameoka city, Kyoto Prefecture, Japan. Frailty was assessed by the weighted score
      based on the 25-item Kihon-Checklist. The frequency of protein-rich food intake
      was examined as "seafood", "meat", "dairy products", "eggs", and "soy products".
      The outcome of frailty was analyzed with a multiple logistic regression model
      using the frequency of protein-rich food intake. When compared to the first
      quartile, it was observed that there was a significant association between the
      lower adjusted prevalence ratio (PR) for frailty and the frequency of seafood
      intake in the fourth quartile among men (PR 0.64, 95% confidence interval (CI),
      0.42, 0.99) and from the second quartile to the third quartile among women (PR
      0.61, 95% CI, 0.43, 0.85; PR 0.64, 95% CI, 0.46, 0.91). The frequency of dairy
      products intake in the third quartile among women was significantly associated
      with a lower PR for frailty (p-value = 0.013). Our findings suggest that the
      consumption of seafood and dairy products may help older adults in maintaining
      their independence.

PMID- 29342875
TI  - The Detection of Burn-Through Weld Defects Using Noncontact Ultrasonics.
AB  - Nearly all manufactured products in the metal industry involve welding. The
      detection and correction of defects during welding improve the product
      reliability and quality, and prevent unexpected failures. Nonintrusive process
      control is critical for avoiding these defects. This paper investigates the
      detection of burn-through damage using noncontact, air-coupled ultrasonics, which
      can be adapted to the immediate and in-situ inspection of welded samples. The
      burn-through leads to a larger volume of degraded weld zone, providing a
      resistance path for the wave to travel which results in lower velocity, energy
      ratio, and amplitude. Wave energy dispersion occurs due to the increase of weld
      burn-through resulting in higher wave attenuation. Weld sample micrographs are
      used to validate the ultrasonic results.

PMID- 29342874
TI  - Rodent Models of Alcoholic Liver Disease: Role of Binge Ethanol Administration.
AB  - Both chronic and acute (binge) alcohol drinking are important health and economic
      concerns worldwide and prominent risk factors for the development of alcoholic
      liver disease (ALD). There are no FDA-approved medications to prevent or to treat
      any stage of ALD. Therefore, discovery of novel therapeutic strategies remains a
      critical need for patients with ALD. Relevant experimental animal models that
      simulate human drinking patterns and mimic the spectrum and severity of alcohol
      induced liver pathology in humans are critical to our ability to identify new
      mechanisms and therapeutic targets. There are several animal models currently in
      use, including the most widely utilized chronic ad libitum ethanol (EtOH) feeding
      (Lieber-DeCarli liquid diet model), chronic intragastric EtOH administration
      (Tsukamoto-French model), and chronic-plus-binge EtOH challenge (Bin Gao-National
      Institute on Alcohol Abuse and Alcoholism (NIAAA) model). This review provides an
      overview of recent advances in rodent models of binge EtOH administration which
      help to recapitulate different features and etiologies of progressive ALD. These
      models include EtOH binge alone, and EtOH binge coupled with chronic EtOH intake,
      a high fat diet, or endotoxin challenge. We analyze the strengths, limitations,
      and translational relevance of these models, as well as summarize the liver
      injury outcomes and mechanistic insights. We further discuss the application(s)
      of binge EtOH models in examining alcohol-induced multi-organ pathology, sex- and
      age-related differences, as well as circadian rhythm disruption.

PMID- 29342876
TI  - Improvement of Verticillium Wilt Resistance by Applying Arbuscular Mycorrhizal
      Fungi to a Cotton Variety with High Symbiotic Efficiency under Field Conditions.
AB  - Arbuscular mycorrhizal fungi (AMF) play an important role in nutrient cycling
      processes and plant stress resistance. To evaluate the effect of Rhizophagus
      irregularis CD1 on plant growth promotion (PGP) and Verticillium wilt disease,
      the symbiotic efficiency of AMF (SEA) was first investigated over a range of 3%
      to 94% in 17 cotton varieties. The high-SEA subgroup had significant PGP effects
      in a greenhouse. From these results, the highest-SEA variety of Lumian 1 was
      selected for a two-year field assay. Consistent with the performance from the
      greenhouse, the AMF-mediated PGP of Lumian 1 also produced significant results,
      including an increased plant height, stem diameter, number of petioles, and
      phosphorus content. Compared with the mock treatment, AMF colonization obviously
      inhibited the symptom development of Verticillium dahliae and more strongly
      elevated the expression of pathogenesis-related genes and lignin synthesis
      related genes. These results suggest that AMF colonization could lead to the
      mycorrhiza-induced resistance (MIR) of Lumian 1 to V. dahliae. Interestingly, our
      results indicated that the AMF endosymbiont could directly inhibit the growth of
      phytopathogenic fungi including V. dahliae by releasing undefined volatiles. In
      summary, our results suggest that stronger effects of AMF application result from
      the high-SEA.

PMID- 29342877
TI  - Accumulation of Heavy Metals in Tea Leaves and Potential Health Risk Assessment:
      A Case Study from Puan County, Guizhou Province, China.
AB  - This study features a survey of the concentrations of aluminum (Al) and heavy
      metals (Mn, Pb, Cd, Hg, As, Cr, Ni, Cu, and Zn) in tea leaves and the
      corresponding cultivation soils (0-30 cm), carried out in Puan County (Guizhou
      Province, China). The average concentrations of Al, Mn, Pb, Cd, Hg, As, Cr, Ni,
      Cu, and Zn in the soil were 106 * 103, 214, 20.9, 0.09, 0.12, 17.5, 121, 27.8,
      131.2, and 64 mg.kg-1, respectively. The heavy metals' pollution indexes in the
      soil can be ranked as follows: Cu > Cr > Hg > As > Ni > Zn > Pb > Mn > Cd. The
      soil was moderately polluted by Cu because of the high geochemical background
      value of Cu in the area. The potential environment risk index (RI) showed that
      7.69% out of the total sample sites were within the moderate level. Moreover, the
      ranges of Al, Mn, Pb, Cd, Hg, As, Cr, Ni, Cu, and Zn concentrations in young tea
      leaves were 250-660, 194-1130, 0.107-0.400, 0.012-0.092, 0.014-0.085, 0.073
      0.456, 0.33-1.26, 6.33-14.90, 14.90-26.10, and 35.8-50.3 mg.kg-1, respectively.
      While in mature tea leaves, they were 4300-10,400, 536-4610, 0.560-1.265, 0.040
      0.087, 0.043-0.089, 0.189-0.453, 0.69-2.91, 3.43-14.20, 6.17-16.25, and 9.1-20.0
      mg.kg-1, respectively. Furthermore, the concentrations of Pb, Cu, As, Hg, Cd, and
      Cr in young tea leaves and mature tea leaves were all lower than the standard
      limit values (5.0, 30, 2.0, 0.3, 1.0, and 5.0 mg.kg-1 for Pb, Cu, As, Hg, Cd, and
      Cr, respectively) in China. Besides, the accumulation ability of tea leaves to Mn
      was the strongest, and the average bioconcentration factor (BCF) of Mn in mature
      tea leaves was 12.5. In addition, the average target hazard quotients (THQ) were
      all less than one for the young tea leaves and the average aggregate risk hazard
      index (HI) to adults was 0.272, indicating that there was not a potential health
      risk for adults through the consumption of the infusions brewed by young tea
      leaves. However, for mature tea leaves, the percentage which HI values were above
      one was 38.46%, and the risk to adults via the consumption of mature tea
      infusions were mainly contributed by Mn and Al.

PMID- 29342878
TI  - Improved Photo-Ignition of Carbon Nanotubes/Ferrocene Using a Lipophilic
      Porphyrin under White Power LED Irradiation.
AB  - The aim of this work is to investigate and characterize the photo-ignition
      process of dry multi-walled carbon nanotubes (MWCNTs) mixed with ferrocene
      (FeCp2) powder, using an LED (light-emitting diode) as the light source, a
      combination that has never been used, to the best of our knowledge. The ignition
      process was improved by adding a lipophilic porphyrin (H2Pp) in powder to the
      MWCNTs/FeCp2 mixtures-thus, a lower ignition threshold was obtained. The ignition
      tests were carried out by employing a continuous emission and a pulsed white LED
      in two test campaigns. In the first, two MWCNT typologies, high purity (HP) and
      industrial grade (IG), were used without porphyrin, obtaining, for both, similar
      ignition thresholds. Furthermore, comparing ignition thresholds obtained with the
      LED source with those previously obtained with a Xenon (Xe) lamp, a significant
      reduction was observed. In the second test campaign, ignition tests were carried
      out by means of a properly driven and controlled pulsed XHP70 LED source. The
      minimum ignition energy (MIE) of IG-MWCNTs/FeCp2 samples was determined by
      varying the duration of the light pulse. Experimental results show that ignition
      is obtained with a pulse duration of 110 ms and a MIE density of 266 mJ/cm2. The
      significant reduction of the MIE value (10-40%), observed when H2Pp in powder
      form was added to the MWCNTs/FeCp2 mixtures, was ascribed to the improved
      photoexcitation and charge transfer properties of the lipophilic porphyrin
      molecules.

PMID- 29342881
TI  - Development of Self-Assembled Nanoribbon Bound Peptide-Polyaniline Composite
      Scaffolds and Their Interactions with Neural Cortical Cells.
AB  - Degenerative neurological disorders and traumatic brain injuries cause
      significant damage to quality of life and often impact survival. As a result,
      novel treatments are necessary that can allow for the regeneration of neural
      tissue. In this work, a new biomimetic scaffold was designed with potential for
      applications in neural tissue regeneration. To develop the scaffold, we first
      prepared a new bolaamphiphile that was capable of undergoing self-assembly into
      nanoribbons at pH 7. Those nanoribbons were then utilized as templates for
      conjugation with specific proteins known to play a critical role in neural tissue
      growth. The template (Ile-TMG-Ile) was prepared by conjugating
      tetramethyleneglutaric acid with isoleucine and the ability of the bolaamphiphile
      to self-assemble was probed at a pH range of 4 through 9. The nanoribbons formed
      under neutral conditions were then functionalized step-wise with the basement
      membrane protein laminin, the neurotropic factor artemin and Type IV collagen.
      The conductive polymer polyaniline (PANI) was then incorporated through
      electrostatic and pi-pi stacking interactions to the scaffold to impart
      electrical properties. Distinct morphology changes were observed upon conjugation
      with each layer, which was also accompanied by an increase in Young's Modulus as
      well as surface roughness. The Young's Modulus of the dried PANI-bound
      biocomposite scaffolds was found to be 5.5 GPa, indicating the mechanical
      strength of the scaffold. Thermal phase changes studied indicated broad
      endothermic peaks upon incorporation of the proteins which were diminished upon
      binding with PANI. The scaffolds also exhibited in vitro biodegradable behavior
      over a period of three weeks. Furthermore, we observed cell proliferation and
      short neurite outgrowths in the presence of rat neural cortical cells, confirming
      that the scaffolds may be applicable in neural tissue regeneration. The
      electrochemical properties of the scaffolds were also studied by generating I-V
      curves by conducting cyclic voltammetry. Thus, we have developed a new biomimetic
      composite scaffold that may have potential applications in neural tissue
      regeneration.

PMID- 29342879
TI  - Ophthalmic Drug Delivery Systems for Antibiotherapy-A Review.
AB  - The last fifty years, ophthalmic drug delivery research has made much progress,
      challenging scientists about the advantages and limitations of this drug delivery
      approach. Topical eye drops are the most commonly used formulation in ocular drug
      delivery. Despite the good tolerance for patients, this topical administration is
      only focus on the anterior ocular diseases and had a high precorneal loss of
      drugs due to the tears production and ocular barriers. Antibiotics are popularly
      used in solution or in ointment for the ophthalmic route. However, their local
      bioavailability needs to be improved in order to decrease the frequency of
      administrations and the side effects and to increase their therapeutic
      efficiency. For this purpose, sustained release forms for ophthalmic delivery of
      antibiotics were developed. This review briefly describes the ocular
      administration with the ocular barriers and the currently topical forms. It
      focuses on experimental results to bypass the limitations of ocular antibiotic
      delivery with new ocular technology as colloidal and in situ gelling systems or
      with the improvement of existing forms as implants and contact lenses.
      Nanotechnology is presently a promising drug delivery way to provide protection
      of antibiotics and improve pathway through ocular barriers and deliver drugs to
      specific target sites.

PMID- 29342883
TI  - Development of SiC Nanoparticles and Second Phases Synergistically Reinforced Mg
      Based Composites Processed by Multi-Pass Forging with Varying Temperatures.
AB  - In this study, SiC nanoparticles were added into matrix alloy through a
      combination of semisolid stirring and ultrasonic vibration while dynamic
      precipitation of second phases was obtained through multi-pass forging with
      varying temperatures. During single-pass forging of the present composite, as the
      deformation temperature increased, the extent of recrystallization increased, and
      grains were refined due to the inhibition effect of the increasing amount of
      dispersed SiC nanoparticles. A small amount of twins within the SiC nanoparticle
      dense zone could be found while the precipitated phases of Mg17Al12 in long
      strips and deformation bands with high density dislocations were formed in the
      particle sparse zone after single-pass forging at 350  degrees C. This indicated
      that the particle sparse zone was mainly deformed by dislocation slip while the
      nanoparticle dense zone may have been deformed by twinning. The yield strength
      and ultimate tensile strength of the composites were gradually enhanced through
      increasing the single-pass forging temperature from 300  degrees C to 400 
      degrees C, which demonstrated that initial high forging temperature contributed
      to the improvement of the mechanical properties. During multi-pass forging with
      varying temperatures, the grain size of the composite was gradually decreased
      while the grain size distribution tended to be uniform with reducing the
      deformation temperature and extending the forging passes. In addition, the amount
      of precipitated second phases was significantly increased compared with that
      after multi-pass forging under a constant temperature. The improvement in the
      yield strength of the developed composite was related to grain refinement
      strengthening and Orowan strengthening resulting from synergistical effect of the
      externally applied SiC nanoparticles and internally precipitated second phases.

PMID- 29342884
TI  - Effect of the Extraction Process on the Biological Activity of Lyophilized
      Apricot Extracts Recovered from Apricot Pomace.
AB  - The preservation of polyphenols in fruits by lyophilization has gained great
      interest in the recent decades. The present study aims to assess the impact of
      the pre-treatment extraction methods heat-assisted extraction (HAE) and infrared
      (IR) on lyophilized apricot pomace extracts. Then to test the conservation of
      polyphenols quantities as well as their bioactivities (antiradical and
      antibacterial) in lyophilized extract. An aqueous extract was obtained through
      either heat-assisted extraction or infrared pre-treatments then lyophilized to
      obtain a dried form. Results showed that the content of polyphenols, the
      antiradical and antibacterial activities in lyophilized extracts exhibited a
      slighter decrease in infrared sample compared to the heat-assisted extraction
      ones. The High-performance liquid chromatography (HPLC) analysis showed that
      lyophilized extracts IR and HAE preserved the same phenolic molecules (rutin,
      catechin and epicatechin) detected in liquid extracts (IR and HAE) with a smaller
      yield. Lyophilization can be used as a widely process in the food industry to
      conserve many bioactive molecules.

PMID- 29342882
TI  - Implication of Soluble Forms of Cell Adhesion Molecules in Infectious Disease and
      Tumor: Insights from Transgenic Animal Models.
AB  - Cell adhesion molecules (CAMs) are surface ligands, usually glycoproteins, which
      mediate cell-to-cell adhesion. They play a critical role in maintaining tissue
      integrity and mediating migration of cells, and some of them also act as viral
      receptors. It has been known that soluble forms of the viral receptors bind to
      the surface glycoproteins of the viruses and neutralize them, resulting in
      inhibition of the viral entry into cells. Nectin-1 is one of important CAMs
      belonging to immunoglobulin superfamily and herpesvirus entry mediator (HVEM) is
      a member of the tumor necrosis factor (TNF) receptor family. Both CAMs also act
      as alphaherpesvirus receptor. Transgenic mice expressing the soluble form of
      nectin-1 or HVEM showed almost complete resistance against the
      alphaherpesviruses. As another CAM, sialic acid-binding immunoglobulin-like
      lectins (Siglecs) that recognize sialic acids are also known as an immunoglobulin
      superfamily member. Siglecs play an important role in the regulation of immune
      cell functions in infectious diseases, inflammation, neurodegeneration,
      autoimmune diseases and cancer. Siglec-9 is one of Siglecs and capsular
      polysaccharide (CPS) of group B Streptococcus (GBS) binds to Siglec-9 on
      neutrophils, leading to suppress host immune response and provide a survival
      advantage to the pathogen. In addition, Siglec-9 also binds to tumor-produced
      mucins such as MUC1 to lead negative immunomodulation. Transgenic mice expressing
      the soluble form of Siglec-9 showed significant resistance against GBS infection
      and remarkable suppression of MUC1 expressing tumor proliferation. This review
      describes recent developments in the understanding of the potency of soluble
      forms of CAMs in the transgenic mice and discusses potential therapeutic
      interventions that may alter the outcomes of certain diseases.

PMID- 29342887
TI  - A Novel Synthesis Routine for Woodwardite and Its Affinity towards Light (La, Ce,
      Nd) and Heavy (Gd and Y) Rare Earth Elements.
AB  - A synthetic Cu-Al-SO4 layered double hydroxide (LDH), analogue to the mineral
      woodwardite [Cu1-xAlx(SO4)x/2(OH)2.nH2O], with x < 0.5 and n <= 3x/2, was
      synthesised by adding a solution of Cu and Al sulphates to a solution with NaOH.
      The pH values were kept constant at 8.0 and 10.0 by a continuous addition of
      NaOH. The material obtained had poor crystallinity, turbostratic structure, and
      consisted of nanoscopic crystallites. The analyses performed in order to
      characterise the obtained materials (X-ray diffraction (XRD), thermogravimetry
      (TG), and Fourier Transform Infra-Red (FTIR) spectroscopy) showed that the Cu-Al
      SO4 LDH is very similar to woodwardite, although it has a smaller layer spacing,
      presumably due to a lesser water content than in natural samples. The synthesis
      was performed by adding light rare earth elements (LREEs) (La, Ce, and Nd) and
      heavy rare earth elements (HREEs) (Gd and Y) in order to test the affinity of the
      Cu-Al-SO4 LDH to the incorporation of REEs. The concentration of rare earth
      elements (REEs) in the solid fraction was in the range of 3.5-8 wt %. The results
      showed a good affinity for HREE and Nd, especially for materials synthesised at
      pH 10.0, whereas the affinities for Ce and La were much lower or non-existent.
      The thermal decomposition of the REE-doped materials generates a mixture of Cu,
      Al, and REE oxides, making them interesting as precursors in REE oxide synthesis.

PMID- 29342886
TI  - A Xylenol Orange-Based Screening Assay for the Substrate Specificity of Flavin
      Dependent para-Phenol Oxidases.
AB  - Vanillyl alcohol oxidase (VAO) and eugenol oxidase (EUGO) are flavin-dependent
      enzymes that catalyse the oxidation of para-substituted phenols. This makes them
      potentially interesting biocatalysts for the conversion of lignin-derived
      aromatic monomers to value-added compounds. To facilitate their biocatalytic
      exploitation, it is important to develop methods by which variants of the enzymes
      can be rapidly screened for increased activity towards substrates of interest.
      Here, we present the development of a screening assay for the substrate
      specificity of para-phenol oxidases based on the detection of hydrogen peroxide
      using the ferric-xylenol orange complex method. The assay was used to screen the
      activity of VAO and EUGO towards a set of twenty-four potential substrates. This
      led to the identification of 4-cyclopentylphenol as a new substrate of VAO and
      EUGO and 4-cyclohexylphenol as a new substrate of VAO. Screening of a small
      library of VAO and EUGO active-site variants for alterations in their substrate
      specificity led to the identification of a VAO variant (T457Q) with increased
      activity towards vanillyl alcohol (4-hydroxy-3-methoxybenzyl alcohol) and a EUGO
      variant (V436I) with increased activity towards chavicol (4-allylphenol) and 4
      cyclopentylphenol. This assay provides a quick and efficient method to screen the
      substrate specificity of para-phenol oxidases, facilitating the enzyme
      engineering of known para-phenol oxidases and the evaluation of the substrate
      specificity of novel para-phenol oxidases.

PMID- 29342885
TI  - Alcohol-Derived Acetaldehyde Exposure in the Oral Cavity.
AB  - Alcohol is classified by the International Agency for Research on Cancer (IARC)
      as a human carcinogen and its consumption has been associated to an increased
      risk of liver, breast, colorectum, and upper aerodigestive tract (UADT) cancers.
      Its mechanisms of carcinogenicity remain unclear and various hypotheses have been
      formulated depending on the target organ considered. In the case of UADT cancers,
      alcohol's major metabolite acetaldehyde seems to play a crucial role.
      Acetaldehyde reacts with DNA inducing modifications, which, if not repaired, can
      result in mutations and lead to cancer development. Despite alcohol being mainly
      metabolized in the liver, several studies performed in humans found higher levels
      of acetaldehyde in saliva compared to those found in blood immediately after
      alcohol consumption. These results suggest that alcohol-derived acetaldehyde
      exposure may occur in the oral cavity independently from liver metabolism. This
      hypothesis is supported by our recent results showing the presence of
      acetaldehyde-related DNA modifications in oral cells of monkeys and humans
      exposed to alcohol, overall suggesting that the alcohol metabolism in the oral
      cavity is an independent cancer risk factor. This review article will focus on
      illustrating the factors modulating alcohol-derived acetaldehyde exposure and
      effects in the oral cavity.

PMID- 29342888
TI  - Surface Properties of Nanostructured, Porous ZnO Thin Films Prepared by Direct
      Current Reactive Magnetron Sputtering.
AB  - In this paper, the results of detailed X-ray photoelectron spectroscopy (XPS)
      studies combined with atomic force microscopy (AFM) investigation concerning the
      local surface chemistry and morphology of nanostructured ZnO thin films are
      presented. They have been deposited by direct current (DC) reactive magnetron
      sputtering under variable absolute Ar/O2 flows (in sccm): 3:0.3; 8:0.8; 10:1;
      15:1.5; 20:2, and 30:3, respectively. The XPS studies allowed us to obtain the
      information on: (1) the relative concentrations of main elements related to their
      surface nonstoichiometry; (2) the existence of undesired C surface
      contaminations; and (3) the various forms of surface bondings. It was found that
      only for the nanostructured ZnO thin films, deposited under extremely different
      conditions, i.e., for Ar/O2 flow ratio equal to 3:0.3 and 30:3 (in sccm),
      respectively, an evident and the most pronounced difference had been observed.
      The same was for the case of AFM experiments. What is crucial, our experiments
      allowed us to find the correlation mainly between the lowest level of C
      contaminations and the local surface morphology of nanostructured ZnO thin films
      obtained at the highest Ar/O2 ratio (30:3), for which the densely packaged
      (agglomerated) nanograins were observed, yielding a smaller surface area for
      undesired C adsorption. The obtained information can help in understanding the
      reason of still rather poor gas sensor characteristics of ZnO based
      nanostructures including the undesired ageing effect, being of a serious barrier
      for their potential application in the development of novel gas sensor devices.

PMID- 29342890
TI  - Polymer-Ceramic Composite Scaffolds: The Effect of Hydroxyapatite and beta-tri
      Calcium Phosphate.
AB  - The design of bioactive scaffolds with improved mechanical and biological
      properties is an important topic of research. This paper investigates the use of
      polymer-ceramic composite scaffolds for bone tissue engineering. Different
      ceramic materials (hydroxyapatite (HA) and beta-tri-calcium phosphate (TCP)) were
      mixed with poly-epsilon-caprolactone (PCL). Scaffolds with different material
      compositions were produced using an extrusion-based additive manufacturing
      system. The produced scaffolds were physically and chemically assessed,
      considering mechanical, wettability, scanning electron microscopy and thermal
      gravimetric tests. Cell viability, attachment and proliferation tests were
      performed using human adipose derived stem cells (hADSCs). Results show that
      scaffolds containing HA present better biological properties and TCP scaffolds
      present improved mechanical properties. It was also possible to observe that the
      addition of ceramic particles had no effect on the wettability of the scaffolds.

PMID- 29342891
TI  - Influence of the Composition, Structure, and Physical and Chemical Properties of
      Aluminium-Oxide-Based Sorbents on Water Adsorption Ability.
AB  - Interaction between the water adsorption ability of aluminium-oxide-based
      sorbents and their chemical composition, acid-base properties of the surface, and
      textural characteristics has been analysed. Alumina desiccants were synthesized
      with the centrifugal-thermal activation of gibbsite followed by the hydration of
      the gibbsite under mild conditions. It was demonstrated that the multicyclic
      adsorption regeneration of samples under realistic conditions results in
      structural transformations and changes in the acidity of their surfaces and water
      adsorption ability. The modification of pseudoboehmite with alkali ions increases
      surface basicity and the dynamic capacity of adsorbents relating to water
      vapours. Equations have been presented that describe the adsorption and
      desorption processes taking place during water vapour adsorption with the
      materials studied.

PMID- 29342892
TI  - Next Generation Wireless Technologies for Internet of Things.
AB  - In the fast-growing Internet of Things (IoT)[...].

PMID- 29342889
TI  - A Case-Control Study of the Genetic Variability in Reactive Oxygen Species
      Metabolizing Enzymes in Melanoma Risk.
AB  - Recent studies have shown that ultraviolet (UV)-induced chemiexcitation of
      melanin fragments leads to DNA damage; and chemiexcitation of melanin fragments
      requires reactive oxygen species (ROS), as ROS excite an electron in the melanin
      fragments. In addition, ROS also cause DNA damages on their own. We hypothesized
      that ROS producing and metabolizing enzymes were major contributors in UV-driven
      melanomas. In this case-control study of 349 participants, we genotyped 23
      prioritized single nucleotide polymorphisms (SNPs) in nicotinamide adenine
      dinucleotide phosphate (NADPH) oxidases 1 and 4 (NOX1 and NOX4, respectively),
      CYBA, RAC1, superoxide dismutases (SOD1, SOD2, and SOD3) and catalase (CAT), and
      analyzed their associated melanoma risk. Five SNPs, namely rs1049255 (CYBA),
      rs4673 (CYBA), rs10951982 (RAC1), rs8031 (SOD2), and rs2536512 (SOD3), exhibited
      significant genotypic frequency differences between melanoma cases and healthy
      controls. In simple logistic regression, RAC1 rs10951982 (odds ratio (OR) 8.98,
      95% confidence interval (CI): 5.08 to 16.44; p < 0.001) reached universal
      significance (p = 0.002) and the minor alleles were associated with increased
      risk of melanoma. In contrast, minor alleles in SOD2 rs8031 (OR 0.16, 95% CI:
      0.06 to 0.39; p < 0.001) and SOD3 rs2536512 (OR 0.08, 95% CI: 0.01 to 0.31; p =
      0.001) were associated with reduced risk of melanoma. In multivariate logistic
      regression, RAC1 rs10951982 (OR 6.15, 95% CI: 2.98 to 13.41; p < 0.001) remained
      significantly associated with increased risk of melanoma. Our results highlighted
      the importance of RAC1, SOD2, and SOD3 variants in the risk of melanoma.

PMID- 29342893
TI  - QTL Mapping for Fiber Quality and Yield Traits Based on Introgression Lines
      Derived from Gossypium hirsutum * G. tomentosum.
AB  - The tetraploid species Gossypium hirsutum is cultivated widely throughout the
      world with high yield and moderate fiber quality, but its genetic basis is
      narrow. A set of 107 introgression lines (ILs) was developed with an
      interspecific cross using G. hirsutumacc. 4105 as the recurrent parent and G.
      tomentosum as the donor parent. A specific locus amplified fragment sequencing
      (SLAF-seq) strategy was used to obtain high-throughput single nucleotide
      polymorphism (SNP) markers. In total, 3157 high-quality SNP markers were obtained
      and further used for identification of quantitative trait loci (QTLs) for fiber
      quality and yield traits evaluated in multiple environments. In total, 74 QTLs
      were detected that were associated with five fiber quality traits (30 QTLs) and
      eight yield traits (44 QTLs), with 2.02-30.15% of the phenotypic variance
      explained (PVE), and 69 markers were found to be associated with these thirteen
      traits. Eleven chromosomes in the A sub-genome (At) harbored 47 QTLs, and nine
      chromosomes in the D sub-genome (Dt) harbored 27 QTLs. More than half (44 QTLs =
      59.45%) showed positive additive effects for fiber and yield traits. Five QTL
      clusters were identified, with three in the At, comprised of thirteen QTLs, and
      two in the Dt comprised of seven QTLs. The ILs developed in this study and the
      identified QTLs will facilitate further molecular breeding for improvement of
      Upland cotton in terms of higher yield with enhanced fiber quality.

PMID- 29342894
TI  - Crystallization of TiO2 Nanotubes by In Situ Heating TEM.
AB  - The thermally-induced crystallization of anodically grown TiO2 amorphous
      nanotubes has been studied so far under ambient pressure conditions by techniques
      such as differential scanning calorimetry and in situ X-ray diffraction, then
      looking at the overall response of several thousands of nanotubes in a carpet
      arrangement. Here we report a study of this phenomenon based on an in situ
      transmission electron microscopy approach that uses a twofold strategy. First, a
      group of some tens of TiO2 amorphous nanotubes was heated looking at their
      electron diffraction pattern change versus temperature, in order to determine
      both the initial temperature of crystallization and the corresponding crystalline
      phases. Second, the experiment was repeated on groups of few nanotubes, imaging
      their structural evolution in the direct space by spherical aberration-corrected
      high resolution transmission electron microscopy. These studies showed that,
      differently from what happens under ambient pressure conditions, under the
      microscope's high vacuum (p < 10-5 Pa) the crystallization of TiO2 amorphous
      nanotubes starts from local small seeds of rutile and brookite, which then grow
      up with the increasing temperature. Besides, the crystallization started at
      different temperatures, namely 450 and 380  degrees C, when the in situ heating
      was performed irradiating the sample with electron beam energy of 120 or 300 keV,
      respectively. This difference is due to atomic knock-on effects induced by the
      electron beam with diverse energy.

PMID- 29342895
TI  - Optimization of Extraction Conditions and Characterization of Pepsin-Solubilised
      Collagen from Skin of Giant Croaker (Nibea japonica).
AB  - In the present study, response surface methodology was performed to investigate
      the effects of extraction parameters on pepsin-solubilised collagen (PSC) from
      the skin of the giant croaker Nibea japonica. The optimum extraction conditions
      of PSC were as follows: concentration of pepsin was 1389 U/g, solid-liquid ratio
      was 1:57 and hydrolysis time was 8.67 h. Under these conditions, the extraction
      yield of PSC was up to 84.85%, which is well agreement with the predict value of
      85.03%. The PSC from Nibea japonica skin was then characterized as type I
      collagen by using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS
      PAGE). The fourier transforms infrared spetroscopy (FTIR) analysis revealed that
      PSC maintains its triple-helical structure by the hydrogen bond. All PSCs were
      soluble in the pH range of 1.0-4.0 and decreases in solubility were observed at
      neutral or alkaline conditions. All PSCs had a decrease in solubility in the
      presence of sodium chloride, especially with a concentration above 2%. So, the
      Nibea japonica skin could serve as another potential source of collagen.

PMID- 29342896
TI  - How Does Counselling in a Stationary Health Care Setting Affect the Attendance in
      a Standardised Sports Club Programme? Process Evaluation of a Quasi-Experimental
      Study.
AB  - Actions in partnership across sectors is one principle for the promotion of
      health behaviours. The objective of this study was to describe the participation
      in a sports club-based exercise programme-named JACKPOT-following an intervention
      in a health care setting. Focus was given to the recruitment into JACKPOT, the
      attendance level, and whether the different programme elements were implemented
      as intented. The practicability of the project was also retrospectively rated.
      Participants were 238 inactive people (50% women) between 30 and 65 years of age
      who attended a health resort. Of these, 77% were assigned to the intervention
      group (IG). The recruitment into the 12 JACKPOT sessions and the attendance
      levels were recorded via attendance lists. The implementation of the intervention
      standards was assessed with structured interviews and participatory observation.
      The Pragmatic Explanatory Continuum Indicator Summary (PRECIS)-2 tool served to
      rate the practicability of the project. Almost 50% of the IG subjects attended
      JACKPOT sessions at least once and 54% of the attenders visited >=75% of the 12
      sessions. Some of the programme elements were not delivered fully. The process
      evaluation results showed that the project worked in a real-world setting, and
      also uncovered potential reasons such as incomplete information delivery for the
      moderate recruitment and attendance level.

PMID- 29342897
TI  - Replication Strategy for Spatiotemporal Data Based on Distributed Caching System.
AB  - The replica strategy in distributed cache can effectively reduce user access
      delay and improve system performance. However, developing a replica strategy
      suitable for varied application scenarios is still quite challenging, owing to
      differences in user access behavior and preferences. In this paper, a replication
      strategy for spatiotemporal data (RSSD) based on a distributed caching system is
      proposed. By taking advantage of the spatiotemporal locality and correlation of
      user access, RSSD mines high popularity and associated files from historical user
      access information, and then generates replicas and selects appropriate cache
      node for placement. Experimental results show that the RSSD algorithm is simple
      and efficient, and succeeds in significantly reducing user access delay.

PMID- 29342899
TI  - Smartphone Spectrometers.
AB  - Smartphones are playing an increasing role in the sciences, owing to the
      ubiquitous proliferation of these devices, their relatively low cost, increasing
      processing power and their suitability for integrated data acquisition and
      processing in a 'lab in a phone' capacity. There is furthermore the potential to
      deploy these units as nodes within Internet of Things architectures, enabling
      massive networked data capture. Hitherto, considerable attention has been focused
      on imaging applications of these devices. However, within just the last few
      years, another possibility has emerged: to use smartphones as a means of
      capturing spectra, mostly by coupling various classes of fore-optics to these
      units with data capture achieved using the smartphone camera. These highly novel
      approaches have the potential to become widely adopted across a broad range of
      scientific e.g., biomedical, chemical and agricultural application areas. In this
      review, we detail the exciting recent development of smartphone spectrometer
      hardware, in addition to covering applications to which these units have been
      deployed, hitherto. The paper also points forward to the potentially highly
      influential impacts that such units could have on the sciences in the coming
      decades.

PMID- 29342898
TI  - Associations between Zinc Deficiency and Metabolic Abnormalities in Patients with
      Chronic Liver Disease.
AB  - Zinc (Zn) is an essential trace element which has favorable antioxidant, anti
      inflammatory, and apoptotic effects. The liver mainly plays a crucial role in
      maintaining systemic Zn homeostasis. Therefore, the occurrence of chronic liver
      diseases, such as chronic hepatitis, liver cirrhosis, or fatty liver, results in
      the impairment of Zn metabolism, and subsequently Zn deficiency. Zn deficiency
      causes plenty of metabolic abnormalities, including insulin resistance, hepatic
      steatosis and hepatic encephalopathy. Inversely, metabolic abnormalities like
      hypoalbuminemia in patients with liver cirrhosis often result in Zn deficiency.
      Recent studies have revealed the putative mechanisms by which Zn deficiency
      evokes a variety of metabolic abnormalities in chronic liver disease. Zn
      supplementation has shown beneficial effects on such metabolic abnormalities in
      experimental models and actual patients with chronic liver disease. This review
      summarizes the pathogenesis of metabolic abnormalities deriving from Zn
      deficiency and the favorable effects of Zn administration in patients with
      chronic liver disease. In addition, we also highlight the interactions between Zn
      and other trace elements, vitamins, amino acids, or hormones in such patients.

PMID- 29342900
TI  - Increasing the Intensity over Time of an Electric-Assist Bike Based on the User
      and Route: The Bike Becomes the Gym.
AB  - Nowadays, many citizens have busy days that make finding time for physical
      activity difficult. Thus, it is important to provide citizens with tools that
      allow them to introduce physical activity into their lives as part of the day's
      routine. This article proposes an app for an electric pedal-assist-system (PAS)
      bicycle that increases the pedaling intensity so the bicyclist can achieve higher
      and higher levels of physical activity. The app includes personalized assist
      levels that have been adapted to the user's strength/ability and a profile of the
      route, segmented according to its slopes. Additionally, a social component
      motivates interaction and competition between users based on a scoring system
      that shows the level of their performances. To test the training module, a case
      study in three different European countries lasted four months and included nine
      people who traveled 551 routes. The electric PAS bicycle with the app that
      increases intensity of physical activity shows promise for increasing levels of
      physical activity as a regular part of the day.

PMID- 29342901
TI  - Omega-3 Polyunsaturated Fatty Acids Time-Dependently Reduce Cell Viability and
      Oncogenic MicroRNA-21 Expression in Estrogen Receptor-Positive Breast Cancer
      Cells (MCF-7).
AB  - The omega-3 polyunsaturated fatty acid (n-3 PUFA), alpha-linolenic acid (ALA),
      and its metabolites, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA),
      independently reduce the growth of breast cancer cells in vitro, but the
      mechanisms, which may involve microRNA (miRNA), are still unclear. The expression
      of the oncomiR, miR-21, is reduced by DHA treatment, but the effects of ALA on
      miR-21, alone or combined with EPA and DHA under physiologically relevant
      concentrations, have not been investigated. The effects of ALA alone and +/-EPA
      and DHA at the blood molar ratios seen in either humans (1.0:1.0:2.5,
      ALA:EPA:DHA) or mice (1.0:0.4:3.1, ALA:EPA:DHA) post flaxseed oil consumption
      (containing ALA) were assessed in vitro in MCF-7 breast cancer cells. Cell
      viability and the expression of miR-21 and its molecular target, phosphatase and
      tension homolog (PTEN, gene and protein), at different time points, were
      examined. At 1, 3, 48 and 96 h ALA alone and 24 h animal ratio treatments
      significantly reduced MCF-7 cell viability, while 1 and 3 h ALA alone and human
      and animal ratio treatments all significantly reduced miR-21 expression, and 24 h
      animal ratio treatment reduced miR-21 expression; these effects were not
      associated with changes in PTEN gene or protein expressions. We showed for the
      first time that ALA alone or combined with EPA and DHA at levels seen in human
      and animal blood post-ALA consumption can significantly reduce cell viability and
      modulate miR-21 expression in a time- and concentration-dependent manner, with
      the animal ratio containing higher DHA having a greater effect. The time
      dependency of miR-21 effects suggests the significance of considering time as a
      variable in miRNA studies, particularly of miR-21.

PMID- 29342902
TI  - Design and Testing of a Flexible Inclinometer Probe for Model Tests of Landslide
      Deep Displacement Measurement.
AB  - The physical model test of landslides is important for studying landslide
      structural damage, and parameter measurement is key in this process. To meet the
      measurement requirements for deep displacement in landslide physical models, an
      automatic flexible inclinometer probe with good coupling and large deformation
      capacity was designed. The flexible inclinometer probe consists of several
      gravity acceleration sensing units that are protected and positioned by silicon
      encapsulation, all the units are connected to a 485-comunication bus. By sensing
      the two-axis tilt angle, the direction and magnitude of the displacement for a
      measurement unit can be calculated, then the overall displacement is accumulated
      according to all units, integrated from bottom to top in turn. In the conversion
      from angle to displacement, two spline interpolation methods are introduced to
      correct and resample the data; one is to interpolate the displacement after
      conversion, and the other is to interpolate the angle before conversion; compared
      with the result read from checkered paper, the latter is proved to have a better
      effect, with an additional condition that the displacement curve move up half the
      length of the unit. The flexible inclinometer is verified with respect to its
      principle and arrangement by a laboratory physical model test, and the test
      results are highly consistent with the actual deformation of the landslide model.

PMID- 29342904
TI  - Improved Coarray Interpolation Algorithms with Additional Orthogonal Constraint
      for Cyclostationary Signals.
AB  - Many modulated signals exhibit a cyclostationarity property, which can be
      exploited in direction-of-arrival (DOA) estimation to effectively eliminate
      interference and noise. In this paper, our aim is to integrate the
      cyclostationarity with the spatial domain and enable the algorithm to estimate
      more sources than sensors. However, DOA estimation with a sparse array is
      performed in the coarray domain and the holes within the coarray limit the usage
      of the complete coarray information. In order to use the complete coarray
      information to increase the degrees-of-freedom (DOFs), sparsity-aware-based
      methods and the difference coarray interpolation methods have been proposed. In
      this paper, the coarray interpolation technique is further explored with
      cyclostationary signals. Besides the difference coarray model and its
      corresponding Toeplitz completion formulation, we build up a sum coarray model
      and formulate a Hankel completion problem. In order to further improve the
      performance of the structured matrix completion, we define the spatial spectrum
      sampling operations and the derivative (conjugate) correlation subspaces, which
      can be exploited to construct orthogonal constraints for the autocorrelation
      vectors in the coarray interpolation problem. Prior knowledge of the source
      interval can also be incorporated into the problem. Simulation results
      demonstrate that the additional constraints contribute to a remarkable
      performance improvement.

PMID- 29342903
TI  - Application of Nanoparticle Technologies in the Combat against Anti-Microbial
      Resistance.
AB  - Anti-microbial resistance is a growing problem that has impacted the world and
      brought about the beginning of the end for the old generation of antibiotics.
      Increasingly, more antibiotics are being prescribed unnecessarily and this
      reckless practice has resulted in increased resistance towards these drugs,
      rendering them useless against infection. Nanotechnology presents a potential
      answer to anti-microbial resistance, which could stimulate innovation and create
      a new generation of antibiotic treatments for future medicines. Preserving
      existing antibiotic activity through novel formulation into or onto
      nanotechnologies can increase clinical longevity of action against infection.
      Additionally, the unique physiochemical properties of nanoparticles can provide
      new anti-bacterial modes of action which can also be explored. Simply
      concentrating on antibiotic prescribing habits will not resolve the issue but
      rather mitigate it. Thus, new scientific approaches through the development of
      novel antibiotics and formulations is required in order to employ a new
      generation of therapies to combat anti-microbial resistance.

PMID- 29342905
TI  - Closed-Form Algorithm for 3-D Near-Field OFDM Signal Localization under Uniform
      Circular Array.
AB  - Due to its widespread application in communications, radar, etc., the orthogonal
      frequency division multiplexing (OFDM) signal has become increasingly urgent in
      the field of localization. Under uniform circular array (UCA) and near-field
      conditions, this paper presents a closed-form algorithm based on phase difference
      for estimating the three-dimensional (3-D) location (azimuth angle, elevation
      angle, and range) of the OFDM signal. In the algorithm, considering that it is
      difficult to distinguish the frequency of the OFDM signal's subcarriers and the
      phase-based method is always affected by errors of the frequency estimation, this
      paper employs sparse representation (SR) to obtain the super-resolution
      frequencies and the corresponding phases of subcarriers. Further, as the phase
      differences of the adjacent sensors including azimuth angle, elevation angle and
      range parameters can be expressed as indefinite equations, the near-field OFDM
      signal's 3-D location is obtained by employing the least square method, where the
      phase differences are based on the average of the estimated subcarriers. Finally,
      the performance of the proposed algorithm is demonstrated by several simulations.

PMID- 29342906
TI  - Modelling and Characterization of Effective Thermal Conductivity of Single Hollow
      Glass Microsphere and Its Powder.
AB  - Tiny hollow glass microsphere (HGM) can be applied for designing new light
      weighted and thermal-insulated composites as high strength core, owing to its
      hollow structure. However, little work has been found for studying its own
      overall thermal conductivity independent of any matrix, which generally cannot be
      measured or evaluated directly. In this study, the overall thermal conductivity
      of HGM is investigated experimentally and numerically. The experimental
      investigation of thermal conductivity of HGM powder is performed by the transient
      plane source (TPS) technique to provide a reference to numerical results, which
      are obtained by a developed three-dimensional two-step hierarchical computational
      method. In the present method, three heterogeneous HGM stacking elements
      representing different distributions of HGMs in the powder are assumed. Each
      stacking element and its equivalent homogeneous solid counterpart are,
      respectively, embedded into a fictitious matrix material as fillers to form two
      equivalent composite systems at different levels, and then the overall thermal
      conductivity of each stacking element can be numerically determined through the
      equivalence of the two systems. The comparison of experimental and computational
      results indicates the present computational modeling can be used for effectively
      predicting the overall thermal conductivity of single HGM and its powder in a
      flexible way. Besides, it is necessary to note that the influence of thermal
      interfacial resistance cannot be removed from the experimental results in the TPS
      measurement.

PMID- 29342907
TI  - An Uncommon Case of Pediatric Esthesioneuroblastoma Presenting as SIADH: 18F-FDG
      PET/CT in Staging and Post-Therapeutic Assessment.
AB  - Esthesioneuroblastoma (ENB) is an uncommon neuroendocrine tumor originating from
      the olfactory neuroepithelium and accounts for 3-6% of all intranasal tumors [1].
      ENBs can be locally aggressive and cause invasion and destruction of surrounding
      structures. Histological grading and clinical stage at presentation are highly
      predictive of survival and especially presence of lymph node and distant
      metastases are determining prognostic factors [2,3,4,5]. Thus, reliable imaging
      is essential in these patients. Conventional imaging modalities for staging ENB
      are magnetic resonance imaging (MRI) and computed tomography (CT). However,
      fluorine-18 fluoro-2-deoxy-d-glucose positron emission tomography/CT (18F-FDG
      PET/CT) has been reported as a valuable adjunct and was found to upstage 36% of
      ENB patients compared to conventional imaging [6]. We present a case
      demonstrating the diagnostic work-up and follow-up with 18F-FDG PET/CT in a young
      patient with ENB with a highly atypical clinical presentation.

PMID- 29342908
TI  - Rapid 3D Reconstruction for Image Sequence Acquired from UAV Camera.
AB  - In order to reconstruct three-dimensional (3D) structures from an image sequence
      captured by unmanned aerial vehicles' camera (UAVs) and improve the processing
      speed, we propose a rapid 3D reconstruction method that is based on an image
      queue, considering the continuity and relevance of UAV camera images. The
      proposed approach first compresses the feature points of each image into three
      principal component points by using the principal component analysis method. In
      order to select the key images suitable for 3D reconstruction, the principal
      component points are used to estimate the interrelationships between images.
      Second, these key images are inserted into a fixed-length image queue. The
      positions and orientations of the images are calculated, and the 3D coordinates
      of the feature points are estimated using weighted bundle adjustment. With this
      structural information, the depth maps of these images can be calculated. Next,
      we update the image queue by deleting some of the old images and inserting some
      new images into the queue, and a structural calculation of all the images can be
      performed by repeating the previous steps. Finally, a dense 3D point cloud can be
      obtained using the depth-map fusion method. The experimental results indicate
      that when the texture of the images is complex and the number of images exceeds
      100, the proposed method can improve the calculation speed by more than a factor
      of four with almost no loss of precision. Furthermore, as the number of images
      increases, the improvement in the calculation speed will become more noticeable.

PMID- 29342909
TI  - Spirostane-Type Saponins Obtained from Yucca schidigera.
AB  - It is well known that spirostane-type saponins show various bioactivities. In our
      on-going program of screening these kinds of constituents from natural products,
      Yucca schidigera was found to be rich in them, and nine new spirostanol saponins,
      Yucca spirostanosides A1 (1), A2 (2), B1 (3), B2 (4), B3 (5), C1 (6), C2 (7), C3
      (8), and D1 (9), together with five known ones (10-14) were isolated from the
      plant. Their structures were elucidated by extensive spectroscopic methods,
      including 1D and 2D NMR and MS spectra, and comparing with published data.

PMID- 29342910
TI  - Academic Stress and Self-Regulation among University Students in Malaysia:
      Mediator Role of Mindfulness.
AB  - Academic stress is the most common emotional or mental state that students
      experience during their studies. Stress is a result of a wide range of issues,
      including test and exam burden, a demanding course, a different educational
      system, and thinking about future plans upon graduation. A sizeable body of
      literature in stress management research has found that self-regulation and being
      mindful will help students to cope up with the stress and dodge long-term
      negative consequences, such as substance abuse. The present study aims to
      investigate the influence of academic stress, self-regulation, and mindfulness
      among undergraduate students in Klang Valley, Malaysia, and to identify
      mindfulness as the mediator between academic stress and self-regulation. For this
      study, a total of 384 undergraduate students in Klang Valley, Malaysia were
      recruited. Using Correlational analysis, results revealed that there was a
      significant relationship between academic stress, self-regulation, and
      mindfulness. However, using SPSS mediational analysis, mindfulness did not prove
      the mediator role in the study.

PMID- 29342915
TI  - Correction: An Extended Damage Plasticity Model for Shotcrete: Formulation and
      Comparison with Other Shotcrete Models.
AB  - The authors would like to correct following typing errors: For (3) and (4), the
      correct expressions are given as[...].

PMID- 29342911
TI  - Effects of Acanthopanax senticosus on Brain Injury Induced by Simulated Spatial
      Radiation in Mouse Model Based on Pharmacokinetics and Comparative Proteomics.
AB  - The active compounds in Acanthopanax senticosus (AS) have different
      pharmacokinetic characteristics in mouse models. Cmax and AUC of Acanthopanax
      senticosus polysaccharides (ASPS) were significantly reduced in radiation-injured
      mice, suggesting that the blood flow of mouse was blocked or slowed, due to the
      pathological state of ischemia and hypoxia, which are caused by radiation. In
      contrast, the ability of various metabolizing enzymes to inactivate, capacity of
      biofilm transport decrease, and lessening of renal blood flow accounts for
      radiation, resulting in the accumulation of syringin and eleutheroside E in the
      irradiated mouse. Therefore, there were higher pharmacokinetic parameters-AUC,
      MRT, and t1/2 of the two compounds in radiation-injured mouse, when compared with
      normal mouse. In order to investigate the intrinsic mechanism of AS on radiation
      injury, AS extract's protective effects on brain, the main part of mouse that
      suffered from radiation, were explored. The function of AS extract in repressing
      expression changes of radiation response proteins in prefrontal cortex (PFC) of
      mouse brain included tubulin protein family (alpha-, beta-tubulin subunits),
      dihydropyrimidinase-related protein 2 (CRMP2), gamma-actin, 14-3-3 protein family
      (14-3-3zeta, epsilon), heat shock protein 90beta (HSP90beta), and enolase 2. The
      results demonstrated the AS extract had positive effects on nerve cells'
      structure, adhesion, locomotion, fission, and phagocytosis, through regulating
      various action pathways, such as Hippo, phagosome, PI3K/Akt (phosphatidylinositol
      3 kinase/protein kinase B), Neurotrophin, Rap1 (Ras-related protein RAP-1A), gap
      junction glycolysis/gluconeogenesis, and HIF-1 (Hypoxia-inducible factor 1)
      signaling pathways to maintain normal mouse neurological activity. All of the
      results indicated that AS may be a promising alternative medicine for the
      treatment of radiation injury in mouse brain. It would be tested that whether the
      bioactive ingredients of AS could be effective through the blood-brain barrier in
      the future.

PMID- 29342916
TI  - Coffee Intake and Liver Steatosis: A Population Study in a Mediterranean Area.
AB  - Coffee drinking seems to have several beneficial effects on health outcomes.
      However, the effect on hepatic steatosis, depending on a high alcohol consumption
      (AFLD, alcoholic fatty liver disease) or on metabolic factors (non-alcoholic
      fatty liver disease, NAFLD), is still equivocal. Thus, we aimed to explore the
      potential association between coffee consumption and the presence and severity of
      hepatic steatosis in people with NAFLD or AFLD. In this cross-sectional study,
      coffee drinking was recorded using a semi-quantitative food frequency
      questionnaire, and categorized as yes vs. no and as 0, 1, 2, >=3. The degree of
      fatty liver was assessed through a standardized ultrasound examination (score 0
      to 6, with higher values reflecting higher severity). Liver steatosis was
      classified as NAFLD or AFLD on daily alcohol intake >30 g/day for men and >20
      g/day for women. This study included 2819 middle-aged participants; the great
      majority were coffee drinkers (86.1%). After adjusting for 12 potential
      confounders, drinking coffee was not associated with decreased odds for NAFLD (n
      = 916) (odds ratio, OR = 0.93; 95% confidence intervals, CI: 0.72-1.20) or AFLD
      (n = 276) (OR = 1.20; 95% CI: 0.66-2.0). The consumption of coffee (categorized
      as yes vs. no), or an increased consumption of coffee were not associated with
      the presence of mild, moderate or severe liver steatosis in either NAFLD or AFLD.
      In conclusion, coffee intake was not associated with any lower odds of hepatic
      steatosis in either non-alcoholic or alcoholic forms in this large cohort of
      South Italian individuals.

PMID- 29342917
TI  - Nitrogen-Doped Carbon for Red Phosphorous Based Anode Materials for Lithium Ion
      Batteries.
AB  - Serving as conductive matrix and stress buffer, the carbon matrix plays a pivotal
      role in enabling red phosphorus to be a promising anode material for high
      capacity lithium ion batteries and sodium ion batteries. In this paper, nitrogen
      doping is proved to effective enhance the interface interaction between carbon
      and red phosphorus. In detail, the adsorption energy between phosphorus atoms and
      oxygen-containing functional groups on the carbon is significantly reduced by
      nitrogen doping, as verified by X-ray photoelectron spectroscopy. The adsorption
      mechanisms are further revealed on the basis of DFT (the first density functional
      theory) calculations. The RPNC (red phosphorus/nitrogen-doped carbon composite)
      material shows higher cycling stability and higher capacity than that of RPC (red
      phosphorus/carbon composite) anode. After 100 cycles, the RPNC still keeps
      discharge capacity of 1453 mAh g-1 at the current density of 300 mA g-1 (the
      discharge capacity of RPC after 100 cycles is 1348 mAh g-1). Even at 1200 mA g-1,
      the RPNC composite still delivers a capacity of 1178 mAh g-1. This work provides
      insight information about the interface interactions between composite materials,
      as well as new technology develops high performance phosphorus based anode
      materials.

PMID- 29342919
TI  - Treatment of Sciatica Following Uterine Cancer with Acupuncture: A Case Report.
AB  - For women, gynaecological or obstetrical disorders are second to disc prolapse as
      the most common cause of sciatica. As not many effective conventional treatments
      can be found for sciatica following uterine cancer, patients may seek assistance
      from complementary and alternative medicine. Here, we present a case of a woman
      with severe and chronic sciatica secondary to uterine cancer who experienced
      temporary relief from acupuncture.

PMID- 29342920
TI  - Asbestos Consumption in Mongolia: 1996-2014.
AB  - Asbestos is still used in Mongolia in the energy and construction sectors, among
      others. However, limited data is available on asbestos consumption and asbestos
      related disease in Mongolia. The purpose of this paper is to present the
      available information on the importation of asbestos into Mongolia. We used data
      on annual asbestos imports between 1996 and 2014 from Mongolian Customs
      Statistics and the National Council on Toxic and Hazardous Substances Affairs.
      The uses of this material are also presented with respect to chrysotile alone.
      Most asbestos is used for construction. Mongolia started using asbestos in the
      energy and construction industries as thermal insulation in 1961. Asbestos is
      still allowed for use in Mongolia under the Law on Toxic and Hazards Substances.
      There are no asbestos mines in Mongolia, and the manufacture of asbestos
      containing materials does not take place there. Thus, asbestos is mainly imported
      from China and Russia. Mongolia used 44,422 metric tons of asbestos-containing
      materials between 1996 and 2014. In Mongolia, with the current use of asbestos,
      there will be a continuing risk of developing asbestos-related diseases from past
      use, and proper oversight of asbestos-involving activities and the safe removal
      and disposal of asbestos must be considered.

PMID- 29342918
TI  - Abnormal Sphingolipid World in Inflammation Specific for Lysosomal Storage
      Diseases and Skin Disorders.
AB  - Research in recent years has shown that sphingolipids are essential signalling
      molecules for the proper biological and structural functioning of cells. Long
      term studies on the metabolism of sphingolipids have provided evidence for their
      role in the pathogenesis of a number of diseases. As many inflammatory diseases,
      such as lysosomal storage disorders and some dermatologic diseases, including
      psoriasis, atopic dermatitis and ichthyoses, are associated with the altered
      composition and metabolism of sphingolipids, more studies precisely determining
      the responsibilities of these compounds for disease states are required to
      develop novel pharmacological treatment opportunities. It is worth emphasizing
      that knowledge from the study of inflammatory metabolic diseases and especially
      the possibility of their treatment may lead to insight into related metabolic
      pathways, including those involved in the formation of the epidermal barrier and
      providing new approaches towards workable therapies.

PMID- 29342921
TI  - RNA-Targeted Therapies and Amyotrophic Lateral Sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal motor disease in adults. Its
      pathophysiology remains mysterious, but tremendous advances have been made with
      the discovery of the most frequent mutations of its more common familial form
      linked to the C9ORF72 gene. Although most cases are still considered sporadic,
      these genetic mutations have revealed the role of RNA production, processing and
      transport in ALS, and may be important players in all ALS forms. There are no
      disease-modifying treatments for adult human neurodegenerative diseases,
      including ALS. As in spinal muscular atrophy, RNA-targeted therapies have been
      proposed as potential strategies for treating this neurodegenerative disorder.
      Successes achieved in various animal models of ALS have proven that RNA therapies
      are both safe and effective. With careful consideration of the applicability of
      such therapies in humans, it is possible to anticipate ongoing in vivo research
      and clinical trial development of RNA therapies for treating ALS.

PMID- 29342923
TI  - Electrical Design and Evaluation of Asynchronous Serial Bus Communication Network
      of 48 Sensor Platform LSIs with Single-Ended I/O for Integrated MEMS-LSI Sensors.
AB  - For installing many sensors in a limited space with a limited computing resource,
      the digitization of the sensor output at the site of sensation has advantages
      such as a small amount of wiring, low signal interference and high scalability.
      For this purpose, we have developed a dedicated Complementary Metal-Oxide
      Semiconductor (CMOS) Large-Scale Integration (LSI) (referred to as "sensor
      platform LSI") for bus-networked Micro-Electro-Mechanical-Systems (MEMS)-LSI
      integrated sensors. In this LSI, collision avoidance, adaptation and event-driven
      functions are simply implemented to relieve data collision and congestion in
      asynchronous serial bus communication. In this study, we developed a network
      system with 48 sensor platform LSIs based on Printed Circuit Board (PCB) in a
      backbone bus topology with the bus length being 2.4 m. We evaluated the serial
      communication performance when 48 LSIs operated simultaneously with the
      adaptation function. The number of data packets received from each LSI was almost
      identical, and the average sampling frequency of 384 capacitance channels (eight
      for each LSI) was 73.66 Hz.

PMID- 29342922
TI  - Can EGCG Alleviate Symptoms of Down Syndrome by Altering Proteolytic Activity?
AB  - Down syndrome (DS), also known as "trisomy 21", is a genetic disorder caused by
      the presence of all or part of a third copy of chromosome 21. Silencing these
      extra genes is beyond existing technology and seems to be impractical. A number
      of pharmacologic options have been proposed to change the quality of life and
      lifespan of individuals with DS. It was reported that treatment with
      epigallocatechin gallate (EGCG) improves cognitive performance in animal models
      and in humans, suggesting that EGCG may alleviate symptoms of DS. Traditionally,
      EGCG has been associated with the ability to reduce dual specificity tyrosine
      phosphorylation regulated kinase 1A activity, which is overexpressed in trisomy
      21. Based on the data available in the literature, we propose an additional way
      in which EGCG might affect trisomy 21-namely by modifying the proteolytic
      activity of the enzymes involved. It is known that, in Down syndrome, the nerve
      growth factor (NGF) metabolic pathway is altered: first by downregulating tissue
      plasminogen activator (tPA) that activates plasminogen to plasmin, an enzyme
      converting proNGF to mature NGF; secondly, overexpression of metalloproteinase 9
      (MMP-9) further degrades NGF, lowering the amount of mature NGF. EGCG inhibits
      MMP-9, thus protecting NGF. Urokinase (uPA) and tPA are activators of
      plasminogen, and uPA is inhibited by EGCG, but regardless of their structural
      similarity tPA is not inhibited. In this review, we describe mechanisms of
      proteolytic enzymes (MMP-9 and plasminogen activation system), their role in Down
      syndrome, their inhibition by EGCG, possible degradation of this polyphenol and
      the ability of EGCG and its degradation products to cross the blood-brain
      barrier. We conclude that known data accumulated so far provide promising
      evidence of MMP-9 inhibition by EGCG in the brain, which could slow down the
      abnormal degradation of NGF.

PMID- 29342924
TI  - Estrogen and Thyroid Hormone Receptor Activation by Medicinal Plants from Bahia,
      Brazil.
AB  - Background: A number of medicinal plants are traditionally used for metabolic
      disorders in Bahia state, Brazil. The aim of this study was to evaluate the
      estrogen receptor (ER) and thyroid receptor (TR) activation of crude extracts
      prepared from 20 plants. Methods: Species were extracted and assayed for receptor
      activation through both ER and TR gene-reporter assays, using 17beta-estradiol
      and triiodothyronine (T3), respectively, as the positive controls. Results:
      Cajanus cajan (Fabaceae), Abarema cochliacarpus (Fabaceae), and Borreria
      verticillata (Rubiaceae) were able to activate ER as much as the positive control
      (17beta-estradiol). These three plant species were also assayed for TR
      activation. At the concentration of 50 ug/mL, C. cajans exerted the highest
      positive modulation on TR, causing an activation of 59.9%, while B. verticillata
      and A. cochliacarpus caused 30.8% and 23.3%, respectively. Conclusions: Our
      results contribute towards the validation of the traditional use of C. cajans, B.
      verticillata, and A. cochliacarpus in the treatment of metabolic disorders
      related to ER and TR functions. The gene-reporter assay was proven effective in
      screening crude plant extracts for ER/TR activation, endorsing this methodology
      as an important tool for future bioprospection studies focused on identifying
      novel starting molecules for the development of estrogen and thyroid agonists.

PMID- 29342925
TI  - Synergistic Effect of Metal Oxide Nanoparticles on Cell Viability and Activation
      of MAP Kinases and NFkappaB.
AB  - In recent years, there has been an increase in the production of several types of
      nanoparticles (Nps) for different purposes. Several studies have been performed
      to analyse the toxicity induced by some of these individual Nps, but data are
      scarce on the potential hazards or beneficial effects induced by a range of
      nanomaterials in the same environment. The purpose of the study described here
      was to evaluate the toxicological effects induced by in vitro exposure of human
      cells to ZnO Nps in combination with different concentrations of other metal
      oxide Nps (Al2O3, CeO2, TiO2 and Y2O3). The results indicate that the presence of
      these Nps has synergistic or antagonistic effects on the cell death induced by
      ZnO Nps, with a quite marked beneficial effect observed when high concentrations
      of Nps were tested. Moreover, analysis by Western blot of the main components of
      the intracellular activation routes (MAPKs and NFkappaB) again showed that the
      presence of other Nps can affect cell activation. In conclusion, the presence of
      several Nps in the same environment modifies the functional activity of one
      individual Np. Further studies are required in order to elucidate the effects
      induced by combinations of nanomaterials.

PMID- 29342926
TI  - Envelope Correction of Micro-Motion Targets in the Terahertz ISAR Imaging.
AB  - Motion compensation is a crucial step to inverse synthetic aperture radar
      imaging, and envelope correction is the foundation of motion compensation.
      Research on envelope correction based on the small-angle imaging model has
      matured after years of development. However, the small-angle imaging model is not
      applicable to parameter estimation and imaging of micro-motion targets. According
      to the characteristics of the micro-motion targets and the superiorities of
      terahertz imaging radar, an envelope correction method for micro-motion targets
      in the terahertz region was proposed in this paper, including the jump error
      correction based on periodic correction and drift error compensation based on
      nonlinear fitting. Then a 330 GHz imaging radar and two experiments on corner
      reflectors and a warhead model were introduced. The validity of the method was
      verified by the experimental results, and the performance of the method was
      proved by the inverse Radon transform of the range profile sequences.

PMID- 29342927
TI  - The Application of Adaptive Behaviour Models: A Systematic Review.
AB  - Adaptive behaviour has been viewed broadly as an individual's ability to meet the
      standards of social responsibilities and independence; however, this definition
      has been a source of debate amongst researchers and clinicians. Based on the rich
      history and the importance of the construct of adaptive behaviour, the current
      study aimed to provide a comprehensive overview of the application of adaptive
      behaviour models to assessment tools, through a systematic review. A plethora of
      assessment measures for adaptive behaviour have been developed in order to
      adequately assess the construct; however, it appears that the only definition on
      which authors seem to agree is that adaptive behaviour is what adaptive behaviour
      scales measure. The importance of the construct for diagnosis, intervention and
      planning has been highlighted throughout the literature. It is recommended that
      researchers and clinicians critically review what measures of adaptive behaviour
      they are utilising and it is suggested that the definition and theory is
      revisited.

PMID- 29342928
TI  - Protein Oxidation and Sensory Quality of Brine-Injected Pork Loins Added
      Ascorbate or Extracts of Green Tea or Mate during Chill-Storage in High-Oxygen
      Modified Atmosphere.
AB  - Background: Ascorbate is often applied to enhance stability and robustness of
      brine-injected pork chops sold for retail, but may affect protein oxidation,
      while plant extracts are potential substitutes. Methods: Brine-injected pork
      chops (weight-gain ~12%, NaCl ~0.9%) prepared with ascorbate (225 ppm), green tea
      extract (25 ppm gallic acid equivalents (GAE)), or mate extract (25 ppm GAE)
      stored (5  degrees C, seven days) in high-oxygen atmosphere packaging (MAP: 80%
      O2 and 20% CO2) were analyzed for color changes, sensory quality, and protein
      oxidation compared to a control without antioxidant. Results: No significant
      differences were observed for green tea and mate extracts as compared to
      ascorbate when evaluated based on lipid oxidation derived off-flavors, except for
      stale flavor, which mate significantly reduced. All treatments increased the
      level of the protein oxidation product, alpha-aminoadipic semialdehyde as
      compared to the control, and ascorbate was further found to increase thiol loss
      and protein cross-linking, with a concomitant decrease in the sensory perceived
      tenderness. Conclusions: Green tea and mate were found to equally protect against
      lipid oxidation derived off-flavors, and mate showed less prooxidative activity
      towards proteins as compared to ascorbate, resulting in more tender meat. Mate is
      a valuable substitute for ascorbate in brine-injected pork chops.

PMID- 29342929
TI  - Morphology-Controlled Synthesis of Hematite Nanocrystals and Their Optical,
      Magnetic and Electrochemical Performance.
AB  - A series of alpha-Fe2O3 nanocrystals (NCs) with fascinating morphologies, such as
      hollow nanoolives, nanotubes, nanospindles, and nanoplates, were prepared through
      a simple template-free hydrothermal synthesis process. The results showed that
      the morphologies could be easily controlled by SO42- and H2PO4-. Physical
      property analysis showed that the alpha-Fe2O3 NCs exhibited shape- and size
      dependent ferromagnetic and optical behaviors. The absorption band peak of the
      alpha-Fe2O3 NCs could be tuned from 320 to 610 nm. Furthermore, when applied as
      electrode material for supercapacitor, the hollow olive-structure exhibited the
      highest capacitance (285.9 F.g-1) and an excellent long-term cycling stability
      (93% after 3000 cycles), indicating that it could serve as a candidate electrode
      material for a supercapacitor.

PMID- 29342930
TI  - Allergies in Animals and Humans.
AB  - Allergy to inhalant and food allergens affects many patients worldwide [...].

PMID- 29342932
TI  - Interstitial Glucose and Physical Exercise in Type 1 Diabetes: Integrative
      Physiology, Technology, and the Gap In-Between.
AB  - Continuous and flash glucose monitoring systems measure interstitial fluid
      glucose concentrations within a body compartment that is dramatically altered by
      posture and is responsive to the physiological and metabolic changes that enable
      exercise performance in individuals with type 1 diabetes. Body fluid
      redistribution within the interstitial compartment, alterations in interstitial
      fluid volume, changes in rate and direction of fluid flow between the
      vasculature, interstitium and lymphatics, as well as alterations in the rate of
      glucose production and uptake by exercising tissues, make for caution when
      interpreting device read-outs in a rapidly changing internal environment during
      acute exercise. We present an understanding of the physiological and metabolic
      changes taking place with acute exercise and detail the blood and interstitial
      glucose responses with different forms of exercise, namely sustained endurance,
      high-intensity, and strength exercises in individuals with type 1 diabetes.
      Further, we detail novel technical information on currently available patient
      devices. As more health services and insurance companies advocate their use,
      understanding continuous and flash glucose monitoring for its strengths and
      limitations may offer more confidence for patients aiming to manage glycemia
      around exercise.

PMID- 29342931
TI  - Transcriptome Analysis Based on RNA-Seq in Understanding Pathogenic Mechanisms of
      Diseases and the Immune System of Fish: A Comprehensive Review.
AB  - In recent years, with the advent of next-generation sequencing along with the
      development of various bioinformatics tools, RNA sequencing (RNA-Seq)-based
      transcriptome analysis has become much more affordable in the field of biological
      research. This technique has even opened up avenues to explore the transcriptome
      of non-model organisms for which a reference genome is not available. This has
      made fish health researchers march towards this technology to understand
      pathogenic processes and immune reactions in fish during the event of infection.
      Recent studies using this technology have altered and updated the previous
      understanding of many diseases in fish. RNA-Seq has been employed in the
      understanding of fish pathogens like bacteria, virus, parasites, and oomycetes.
      Also, it has been helpful in unraveling the immune mechanisms in fish.
      Additionally, RNA-Seq technology has made its way for future works, such as
      genetic linkage mapping, quantitative trait analysis, disease-resistant strain or
      broodstock selection, and the development of effective vaccines and therapies.
      Until now, there are no reviews that comprehensively summarize the studies which
      made use of RNA-Seq to explore the mechanisms of infection of pathogens and the
      defense strategies of fish hosts. This review aims to summarize the contemporary
      understanding and findings with regard to infectious pathogens and the immune
      system of fish that have been achieved through RNA-Seq technology.

PMID- 29342933
TI  - In Vitro Anticoagulant Activity and Active Components of Safflower Injection.
AB  - Safflower injection is well-known as a traditional Chinese medicine used to
      improve the blood circulation. In this study, seven safflower injection samples
      from different companies were evaluated for their in vitro anticoagulant activity
      by measuring their activated partial thromboplastin time (APTT) and prothrombin
      time (PT) against human plasma. The screening results suggested that the
      safflower injections exhibited a significant prolonging influence on APTT (p <
      0.05 vs. the control group), but not on prolonging PT (p > 0.05 vs. the control
      group). The safflower injection was separated into four fractions, and among
      them, fraction four demonstrated the most anticoagulant activity, with an APTT of
      95.4 +/- 1.4 s at a concentration of 4.0 MUg/MUL (p < 0.01 vs. control group). In
      addition, three active components, p-hydroxybenzaldehyde, p-hydroxy-cinnamic
      acid, and (8Z)-decaene-4,6-diyne-1-O-beta-d-glucopyranoside were isolated from
      fraction four with Sephadex LH-20 and C18 column chromatography. All three active
      components showed significant prolonging of APTT (p < 0.05 vs. control group).
      Among them, p-hydroxy-cinnamic acid exhibited the most activity (p < 0.01 vs.
      control group). The results indicated that safflower injection strongly affects
      the intrinsic coagulation system, and we suggest that this might be the mechanism
      by which the safflower injection activates and promotes blood circulation.

PMID- 29342934
TI  - Exploring Positive Survivorship Experiences of Indigenous Australian Cancer
      Patients.
AB  - Amongst Indigenous Australians, "cancer" has negative connotations that
      detrimentally impact upon access to cancer care services. Barriers to accessing
      cancer services amongst Indigenous Australians are widely reported. In contrast,
      factors that facilitate this cohort to successfully navigate cancer care services
      ("enablers") are scarcely reported in the literature. Through qualitative
      interviews, this article examines factors that assist Indigenous Australians to
      have positive cancer experiences. Semi-structured interviews were conducted with
      twelve adult Indigenous oncology patients recruited from a tertiary hospital in
      Queensland, Australia during 2012-2014. Data generated from the interviews were
      independently reviewed by two researchers via inductive thematic analytical
      processes. Discussions followed by consensus on the major categories allowed
      conclusions to be drawn on potential enablers. Two major categories of enablers
      were identified by the researchers: resilience and communication. Individual's
      intrinsic strength, their coping strategies, and receipt of support improved
      participant's resilience and consequently supported a positive experience.
      Communication methods and an effective patient-provider relationship facilitated
      positive experiences for participants. Despite potential barriers to access of
      care for Indigenous cancer patients, participants in the study demonstrated that
      it was still possible to focus on the positive aspects of their cancer
      experiences. Many participants explained how cancer changed their outlook on
      life, often for the better, with many feeling empowered as they progressed
      through their cancer diagnosis and treatment processes.

PMID- 29342935
TI  - Exogenous Melatonin Alleviates Cold Stress by Promoting Antioxidant Defense and
      Redox Homeostasis in Camellia sinensis L.
AB  - The unprecedented early spring frost that appears as a cold stress adversely
      affects growth and productivity in tea (Camellia sinensis L.); therefore, it is
      indispensable to develop approaches to improve the cold tolerance of tea. Here,
      we investigated the effect of pretreatment with exogenous melatonin on the net
      photosynthetic rate, the maximum photochemical efficiency of PSII, chlorophyll
      content, lipid peroxidation, reactive oxygen species (ROS) accumulation,
      antioxidant potential, and redox homeostasis in leaves of tea plants following
      cold stress. Our results revealed that cold treatment induced oxidative stress by
      increasing ROS accumulation, which in turn affected the photosynthetic process in
      tea leaves. However, treatment with melatonin mitigated cold-induced reductions
      in photosynthetic capacity by reducing oxidative stress through enhanced
      antioxidant potential and redox homeostasis. This study provides strong evidence
      that melatonin could alleviate cold-induced adverse effects in tea plants.

PMID- 29342936
TI  - Structure Characterization of Honey-Processed Astragalus Polysaccharides and Its
      Anti-Inflammatory Activity In Vitro.
AB  - Honey-processed Astragalus is a dosage form of Radix Astragalus mixed with honey
      by a traditional Chinese medicine processing method which strengthens the tonic
      effect. Astragalus polysaccharide (APS), perform its immunomodulatory effects by
      relying on the tonic effect of Radix Astragalus, therefore, the improved
      pharmacological activity of honey-processed Astragalus polysaccharide (HAPS)
      might be due to structural changes during processing. The molecular weights of
      HAPS and APS were 1,695,788 Da, 2,047,756 Da, respectively, as determined by high
      performance gel filtration chromatography combined with evaporative light
      scattering detection (HPGFC-ELSD). The monosaccharide composition was determined
      by ultra-performance liquid chromatogram quadrupole time-of-flight mass
      spectrometry (UPLC/ESI-Q-TOF-MS) after pre-column derivatization with 1-phenyl-3
      methyl-5-pyrazolone (PMP). The results showed that the essential components were
      mannose, glucose, xylose, arabinose, glucuronic acid and rhamnose, is molar
      ratios of 0.06:28.34:0.58:0.24:0.33:0.21 and 0.27:12.83:1.63:0.71:1.04:0.56,
      respectively. FT-IR and NMR analysis of HAPS results showed the presence of
      uronic acid and acetyl groups. The anti-inflammatory activities of HAPS were more
      effective than those of APS according to the NO contents and the expression of
      IFN-gamma, IL-1beta, IL-22 and TNF-alpha in lipopolysaccharide (LPS)-induced
      RAW264.7 cells. This findings suggest that the anti-inflammatory and bioactivity
      improvement might be associated with molecular structure changes, bearing on the
      potential immunomodulatory action.

PMID- 29342937
TI  - Does a High Sugar High Fat Dietary Pattern Explain the Unequal Burden in
      Prevalence of Type 2 Diabetes in a Multi-Ethnic Population in The Netherlands?
      The HELIUS Study.
AB  - The risk for type 2 diabetes (T2D) in ethnic minorities in Europe is higher in
      comparison with their European host populations. The western dietary pattern,
      characterized by high amounts of sugar and saturated fat (HSHF dietary pattern),
      has been associated with a higher risk for T2D. Information on this association
      in minority populations is scarce. Therefore, we aimed to investigate the HSHF
      dietary pattern and its role in the unequal burden of T2D prevalence in a multi
      ethnic population in The Netherlands. We included 4694 participants aged 18-70
      years of Dutch, South-Asian Surinamese, African Surinamese, Turkish, and Moroccan
      origin from the HELIUS study. Dutch participants scored the highest on the HSHF
      dietary pattern, followed by the Turkish, Moroccan, African Surinamese, and South
      Asian Surinamese participants. Prevalence ratios (PR) for T2D were then
      calculated using multivariate cox regression analyses, adjusted for
      sociodemographic, anthropometric, and lifestyle factors. Higher adherence to an
      HSHF diet was not significantly related to T2D prevalence in the total study
      sample (PR 1.04 high versus low adherence, 95% CI: 0.80-1.35). In line,
      adjustment for HSHF diet score did not explain the ethnic differences in T2D. For
      instance, the PR of the South-Asian Surinamese vs. Dutch changed from 2.76 (95%
      CI: 2.05-3.72) to 2.90 (95% CI: 2.11-3.98) after adjustment for HSHF. To
      conclude, a western dietary pattern high in sugar and saturated fat was not
      associated with T2D, and did not explain the unequal burden in prevalence of T2D
      across the ethnic groups.

PMID- 29342938
TI  - Role of Aquaporins in Determining Carbon and Nitrogen Status in Higher Plants.
AB  - Aquaporins (AQPs) are integral membrane proteins facilitating the transport of
      water and some small neutral molecules across cell membranes. In past years, much
      effort has been made to reveal the location of AQPs as well as their function in
      water transport, photosynthetic processes, and stress responses in higher plants.
      In the present review, we paid attention to the character of AQPs in determining
      carbon and nitrogen status. The role of AQPs during photosynthesis is
      characterized as its function in transporting water and CO2 across the membrane
      of chloroplast and thylakoid; recalculated results from published studies showed
      that over-expression of AQPs contributed to 25% and 50% increases in stomatal
      conductance (gs) and mesophyll conductance (gm), respectively. The nitrogen
      status in plants is regulated by AQPs through their effect on water flow as well
      as urea and NH4+ uptake, and the potential role of AQPs in alleviating ammonium
      toxicity is discussed. At the same time, root and/or shoot AQP expression is
      quite dependent on both N supply amounts and forms. Future research directions
      concerning the function of AQPs in regulating plant carbon and nitrogen status as
      well as C/N balance are also highlighted.

PMID- 29342939
TI  - Deciphering the Evolution and Development of the Cuticle by Studying Lipid
      Transfer Proteins in Mosses and Liverworts.
AB  - When plants conquered land, they developed specialized organs, tissues, and cells
      in order to survive in this new and harsh terrestrial environment. New cell
      polymers such as the hydrophobic lipid-based polyesters cutin, suberin, and
      sporopollenin were also developed for protection against water loss, radiation,
      and other potentially harmful abiotic factors. Cutin and waxes are the main
      components of the cuticle, which is the waterproof layer covering the epidermis
      of many aerial organs of land plants. Although the in vivo functions of the group
      of lipid binding proteins known as lipid transfer proteins (LTPs) are still
      rather unclear, there is accumulating evidence suggesting a role for LTPs in the
      transfer and deposition of monomers required for cuticle assembly. In this
      review, we first present an overview of the data connecting LTPs with cuticle
      synthesis. Furthermore, we propose liverworts and mosses as attractive model
      systems for revealing the specific function and activity of LTPs in the
      biosynthesis and evolution of the plant cuticle.

PMID- 29342942
TI  - A Sensor Dynamic Measurement Error Prediction Model Based on NAPSO-SVM.
AB  - Dynamic measurement error correction is an effective way to improve sensor
      precision. Dynamic measurement error prediction is an important part of error
      correction, and support vector machine (SVM) is often used for predicting the
      dynamic measurement errors of sensors. Traditionally, the SVM parameters were
      always set manually, which cannot ensure the model's performance. In this paper,
      a SVM method based on an improved particle swarm optimization (NAPSO) is proposed
      to predict the dynamic measurement errors of sensors. Natural selection and
      simulated annealing are added in the PSO to raise the ability to avoid local
      optima. To verify the performance of NAPSO-SVM, three types of algorithms are
      selected to optimize the SVM's parameters: the particle swarm optimization
      algorithm (PSO), the improved PSO optimization algorithm (NAPSO), and the
      glowworm swarm optimization (GSO). The dynamic measurement error data of two
      sensors are applied as the test data. The root mean squared error and mean
      absolute percentage error are employed to evaluate the prediction models'
      performances. The experimental results show that among the three tested
      algorithms the NAPSO-SVM method has a better prediction precision and a less
      prediction errors, and it is an effective method for predicting the dynamic
      measurement errors of sensors.

PMID- 29342941
TI  - Development of Optical Fiber Based Measurement System for the Verification of
      Entrance Dose Map in Pencil Beam Scanning Proton Beam.
AB  - This study describes the development of a beam monitoring system for the
      verification of entrance dose map in pencil beam scanning (PBS) proton therapy
      based on fiber optic radiation sensors (FORS) and the validation of this system
      through a feasibility study. The beam monitoring system consisted of 128 optical
      fibers optically coupled to photo-multiplier tubes. The performance of the beam
      monitoring system based on FORS was verified by comparing 2D dose maps of square
      shaped fields of various sizes, which were obtained using conventional dosimeters
      such as MatriXX and EBT3 film, with those measured using FORS. The resulting full
      width at half maximum and penumbra were compared for PBS proton beams, with a
      <=2% difference between each value, indicating that measurements using the
      conventional dosimetric tool corresponded to measurements based on FORS. For
      irregularly-shaped fields, a comparison based on the gamma index between 2D dose
      maps obtained using MatriXX and EBT3 film and the 2D dose map measured by the
      FORS showed passing rates of 96.9 +/- 1.3% and 96.2 +/- 1.9%, respectively,
      confirming that FORS-based measurements for PBS proton therapy agreed well with
      those measured using the conventional dosimetric tools. These results demonstrate
      that the developed beam monitoring system based on FORS is good candidate for
      monitoring the entrance dose map in PBS proton therapy.

PMID- 29342940
TI  - Deoxyschizandrin, Isolated from Schisandra Berries, Induces Cell Cycle Arrest in
      Ovarian Cancer Cells and Inhibits the Protumoural Activation of Tumour-Associated
      Macrophages.
AB  - Deoxyschizandrin, a major lignan of Schisandra berries, has been demonstrated to
      have various biological activities such as antioxidant, hepatoprotective, and
      antidiabetic effects. However, the anti-cancer effects of deoxyschizandrin are
      poorly characterized. In the present study, we investigated the anti-cancer
      effect of deoxyschizandrin on human ovarian cancer cell lines and tumour
      associated macrophages (TAMs). Deoxyschizandrin induced G0/G1 phase cell cycle
      arrest and inhibited cyclin E expression in human ovarian cancer cells.
      Overexpression of cyclin E significantly reversed the deoxyschizandrin-induced
      cell growth inhibition. Interestingly, increased production of reactive oxygen
      species and decreased activation of Akt were observed in A2780 cells treated with
      deoxyschizandrin, and the antioxidant compromised the deoxyschizandrin-induced
      cell growth inhibition and Akt inactivation. Moreover, deoxyschizandrin-induced
      cell growth inhibition was markedly suppressed by Akt overexpression. In
      addition, deoxyschizandrin was found to inhibit the expression of the M2
      phenotype markers CD163 and CD209 in TAMs, macrophages stimulated by the ovarian
      cancer cells. Moreover, expression and production of the tumour-promoting factors
      MMP-9, RANTES, and VEGF, which are highly enhanced in TAMs, was significantly
      suppressed by deoxyschizandrin treatment. Taken together, these data suggest that
      deoxyschizandrin exerts anti-cancer effects by inducing G0/G1 cell cycle arrest
      in ovarian cancer cells and reducing the protumoural phenotype of TAMs.

PMID- 29342943
TI  - The Peptide PnPP-19, a Spider Toxin Derivative, Activates MU-Opioid Receptors and
      Modulates Calcium Channels.
AB  - The synthetic peptide PnPP-19 comprehends 19 amino acid residues and it
      represents part of the primary structure of the toxin delta-CNTX-Pn1c (PnTx2-6),
      isolated from the venom of the spider Phoneutria nigriventer. Behavioural tests
      suggest that PnPP-19 induces antinociception by activation of CB1, MU and delta
      opioid receptors. Since the peripheral and central antinociception induced by
      PnPP-19 involves opioid activation, the aim of this work was to identify whether
      this synthetic peptide could directly activate opioid receptors and investigate
      the subtype selectivity for MU-, delta- and/or kappa-opioid receptors.
      Furthermore, we also studied the modulation of calcium influx driven by PnPP-19
      in dorsal root ganglion neurons, and analyzed whether this modulation was opioid
      mediated. PnPP-19 selectively activates MU-opioid receptors inducing indirectly
      inhibition of calcium channels and hereby impairing calcium influx in dorsal root
      ganglion (DRG) neurons. Interestingly, notwithstanding the activation of opioid
      receptors, PnPP-19 does not induce beta-arrestin2 recruitment. PnPP-19 is the
      first spider toxin derivative that, among opioid receptors, selectively activates
      MU-opioid receptors. The lack of beta-arrestin2 recruitment highlights its
      potential for the design of new improved opioid agonists.

PMID- 29342944
TI  - A Novel Adaptive Modulation Based on Nondata-Aided Error Vector Magnitude in Non
      Line-Of-Sight Condition of Wireless Sensor Network.
AB  - The high demand for multimedia applications in environmental monitoring, invasion
      detection, and disaster aid has led to the rise of wireless sensor network (WSN).
      With the increase of reliability and diversity of information streams, the higher
      requirements on throughput and quality of service (QoS) have been put forward in
      data transmission between two sensor nodes. However, lower spectral efficiency
      becomes a bottleneck in non-line-of-sight (NLOS) transmission of WSN. This paper
      proposes a novel nondata-aided error vector magnitude based adaptive modulation
      (NDA-EVM-AM) to solve the problem. NDA-EVM is considered as a new metric to
      evaluate the quality of NLOS link for adaptive modulation in WSN. By modeling the
      NLOS scenario as the eta - MU fading channel, a closed-form expression for the
      NDA-EVM of multilevel quadrature amplitude modulation (MQAM) signals over the eta
      - MU fading channel is derived, and the relationship between SER and NDA-EVM is
      also formulated. Based on these results, NDA-EVM state machine is designed for
      adaptation strategy. The algorithmic complexity of NDA-EVM-AM is analyzed and the
      outage capacity of NDA-EVM-AM in an NLOS scenario is also given. The performances
      of NDA-EVM-AM are compared by simulation, and the results show that NDA-EVM-AM is
      an effective technique to be used in the NLOS scenarios of WSN. This technique
      can accurately reflect the channel variations and efficiently adjust modulation
      order to better match the channel conditions, hence, obtaining better performance
      in average spectral efficiency.

PMID- 29342945
TI  - Hyperspectral Features of Oil-Polluted Sea Ice and the Response to the
      Contamination Area Fraction.
AB  - Researchers have studied oil spills in open waters using remote sensors, but few
      have focused on extracting reflectance features of oil pollution on sea ice. An
      experiment was conducted on natural sea ice in Bohai Bay, China, to obtain the
      spectral reflectance of oil-contaminated sea ice. The spectral absorption index
      (SAI), spectral peak height (SPH), and wavelet detail coefficient (DWT d5) were
      calculated using stepwise multiple linear regression. The reflectances of some
      false targets were measured and analysed. The simulated false targets were
      sediment, iron ore fines, coal dust, and the melt pool. The measured reflectances
      were resampled using five common sensors (GF-2, Landsat8-OLI, Sentinel3-OLCI,
      MODIS, and AVIRIS). Some significant spectral features could discriminate between
      oil-polluted and clean sea ice. The indices correlated well with the oil area
      fractions. All of the adjusted R2 values exceeded 0.9. The SPH model1, based on
      spectral features at 507-670 and 1627-1746 nm, displayed the best fitting. The
      resampled data indicated that these multi-spectral and hyper-spectral sensors
      could be used to detect crude oil on the sea ice if the effect of noise and
      spatial resolution are neglected. The spectral features and their identified
      changes may provide reference on sensor design and band selection.

PMID- 29342946
TI  - Effects of Alloying Elements on the Formation of Core-Shell-Structured
      Reinforcing Particles during Heating of Al-Ti Powder Compacts.
AB  - To prepare core-shell-structured Ti@compound particle (Ti@compoundp) reinforced
      Al matrix composite via powder thixoforming, the effects of alloying elements,
      such as Si, Cu, Mg, and Zn, on the reaction between Ti powders and Al melt, and
      the microstructure of the resulting reinforcements were investigated during
      heating of powder compacts at 993 K (720  degrees C). Simultaneously, the
      situations of the reinforcing particles in the corresponding semisolid compacts
      were also studied. Both thermodynamic analysis and experiment results all
      indicate that Si participated in the reaction and promoted the formation of Al-Ti
      Si ternary compounds, while Cu, Mg, and Zn did not take part in the reaction and
      facilitated Al3Ti phase to form to different degrees. The first-formed Al-Ti-Si
      ternary compound was tau1 phase, and then it gradually transformed into
      (Al,Si)3Ti phase. The proportion and existing time of tau1 phase all increased as
      the Si content increased. In contrast, Mg had the largest, Cu had the least, and
      Si and Zn had an equivalent middle effect on accelerating the reaction. The
      thicker the reaction shell was, the larger the stress generated in the shell was,
      and thus the looser the shell microstructure was. The stress generated in
      (Al,Si)3Ti phase was larger than that in tau1 phase, but smaller than that in
      Al3Ti phase. So, the shells in the Al-Ti-Si system were more compact than those
      in the other systems, and Si element was beneficial to obtain thick and compact
      compound shells. Most of the above results were consistent to those in the
      semisolid state ones except the product phase constituents in the Al-Ti-Mg system
      and the reaction rate in the Al-Ti-Zn system. More importantly, the desirable
      core-shell structured Ti@compoundp was only achieved in the semisolid Al-Ti-Si
      system.

PMID- 29342947
TI  - Understanding Tail-Biting in Pigs through Social Network Analysis.
AB  - The objective of this study was to investigate the association between social
      structure and incidence of tail-biting in pigs. Pigs (n = 144, initial weight =
      7.2 +/- 1.57 kg, 4 weeks of age) were grouped based on their litter origin:
      littermates, non-littermates, and half-group of littermates. Six pens (8
      pigs/pen) of each litter origin were studied for 6 weeks. Incidence of tail
      injury and growth performance were monitored. Behavior of pigs was video recorded
      for 6 h at 6 and 8 weeks of age. Video recordings were scanned at 10 min
      intervals to register pigs that were lying together (1) or not (0) in binary
      matrices. Half weight association index was used for social network construction.
      Social network analysis was performed using the UCINET software. Littermates had
      lower network density (0.119 vs. 0.174; p < 0.05), more absent social ties (20
      vs. 12; p < 0.05), and fewer weak social ties (6 vs. 14, p < 0.05) than non
      littermates, indicating that littermates might be less socially connected.
      Fifteen percent of littermates were identified as victimized pigs by tail-biting,
      and no victimized pigs were observed in other treatment groups. These results
      suggest that littermates might be less socially connected among themselves which
      may predispose them to development of tail-biting.

PMID- 29342948
TI  - Micro-Structures and High-Temperature Friction-Wear Performances of Laser Cladded
      Cr-Ni Coatings.
AB  - Cr-Ni coatings with the mass ratios of 17% Cr-83% Ni, 20% Cr-80% Ni and 24% Cr
      76% Ni were fabricated on H13 hot work mould steel using a laser cladding (LC).
      The surface-interface morphologies, chemical elements, surface roughness and
      phase composition of the obtained Cr-Ni coatings were analysed using a scanning
      electron microscope (SEM), energy disperse spectroscopy (EDS), atomic force
      microscope (AFM) and X-ray diffractometer (XRD), respectively. The friction-wear
      properties and wear rates of Cr-Ni coatings with the different mass ratios of Cr
      and Ni at 600  degrees C were investigated, and the worn morphologies and wear
      mechanism of Cr-Ni coatings were analysed. The results show that the phases of Cr
      Ni coatings with mass ratios of 17% Cr-83% Ni, 20% Cr-80% Ni and 24% Cr-76% Ni
      are composed of Cr + Ni single-phases and their compounds at the different
      stoichiometry, the porosities on the Cr-Ni coatings increase with the Cr content
      increasing. The average coefficient of friction (COF) of 17% Cr-83% Ni, 20% Cr
      80% Ni and 24% Cr-76% coatings are 1.10, 0.33 and 0.87, respectively, in which
      the average COF of 20% Cr-80% Ni coating is the lowest, exhibiting the better
      anti-friction performance. The wear rate of 17% Cr-83% Ni, 20% Cr-80% Ni and 24%
      Cr-76% Ni coatings is 4.533 * 10-6, 5.433 * 10-6, and 1.761 * 10-6 N-1.s-1,
      respectively, showing the wear resistance of Cr-Ni coatings at a high temperature
      increases with the Cr content, in which the wear rate is 24% Cr-76% Ni coating
      with the better reducing wear. The wear mechanism of 17% Cr-83% Ni and 20% Cr-80%
      Ni and 24% Cr-76% coatings at 600  degrees C is primarily adhesive wear, and that
      of 24% Cr-76% coating is also accompanied by oxidative wear.

PMID- 29342951
TI  - Microstructure and Tensile Properties of ECAPed Mg-9Al-1Si-1SiC Composites: The
      Influence of Initial Microstructures.
AB  - Mg-9Al-1Si-1SiC composites with various initial microstructures prior to equal
      channel angular pressing (ECAP) were obtained by different pre-treatments
      (without and with homogenization treatment), and the resultant grain size, second
      phase and tensile properties of ECAPed composites were reported. The ECAPed
      composite with homogenization treatment (HT) exhibited finer grain size, higher
      fraction of dynamically recrystallized (DRXed) grains, weaker texture intensity,
      as well as the presence of dynamic precipitated Mg17Al12 phase compared to that
      without HT. Besides, the morphology of pre-existing Mg2Si changed from massive
      like to needle-like in the ECAPed composite with HT. Room-temperature tensile
      test results showed that ultimate tensile strength (UTS), yield strength (YS),
      and elongation (El) of ECAPed composites with HT were 16.1%, 23%, and 27.3%
      larger than that without HT, respectively.

PMID- 29342950
TI  - Recent Advances of Rare-Earth Ion Doped Luminescent Nanomaterials in Perovskite
      Solar Cells.
AB  - Organic-inorganic lead halide based perovskite solar cells have received broad
      interest due to their merits of low fabrication cost, a low temperature solution
      process, and high energy conversion efficiencies. Rare-earth (RE) ion doped
      nanomaterials can be used in perovskite solar cells to expand the range of
      absorption spectra and improve the stability due to its upconversion and
      downconversion effect. This article reviews recent progress in using RE-ion-doped
      nanomaterials in mesoporous electrodes, perovskite active layers, and as an
      external function layer of perovskite solar cells. Finally, we discuss the
      challenges facing the effective use of RE-ion-doped nanomaterials in perovskite
      solar cells and present some prospects for future research.

PMID- 29342949
TI  - Characterization of a Novel Alginate Lyase from Marine Bacterium Vibrio furnissii
      H1.
AB  - Alginate lyases show great potential for industrial and medicinal applications,
      especially as an attractive biocatalyst for the production of oligosaccharides
      with special bioactivities. A novel alginate lyase, AlyH1, from the marine
      bacterium Vibrio furnissii H1, which has been newly isolated from rotten seaweed,
      was purified and characterized. The purified enzyme showed the specific activity
      of 2.40 U/mg. Its molecular mass was 35.8 kDa. The optimal temperature and pH
      were 40  degrees C and pH 7.5, respectively. AlyH1 maintained stability at
      neutral pH (7.0-8.0) and temperatures below 30  degrees C. Metal ions Na+, Mg2+,
      and K+ increased the activity of the enzyme. With sodium alginate as the
      substrate, the Km and Vmax values of AlyH1 were 2.28 mg/mL and 2.81 U/mg,
      respectively. AlyH1 exhibited activities towards both polyguluronate and
      polymannuronate, and preferentially degraded polyguluronate. Products prepared
      from sodium alginate by AlyH1 were displayed to be di-, tri-, and tetra-alginate
      oligosaccharides. A partial amino acid sequence (190 aa) of AlyH1 analysis
      suggested that AlyH1 was an alginate lyase of polysaccharide lyase family 7. The
      sequence showed less than 77% identity to the reported alginate lyases. These
      data demonstrated that AlyH1 could be as a novel and potential candidate in
      application of alginate oligosaccharides production with low polymerization
      degrees.

PMID- 29342952
TI  - A Long-Term Follow-Up of the Efficacy of Nature-Based Therapy for Adults
      Suffering from Stress-Related Illnesses on Levels of Healthcare Consumption and
      Sick-Leave Absence: A Randomized Controlled Trial.
AB  - Stress-related illnesses are a growing health problem in the Western world; which
      also has economic significance for society. As a consequence; there is a growing
      demand for effective treatments. The study investigates the long-term efficacy of
      the Nacadia(r) nature-based therapy (NNBT) by comparing it to the efficacy of a
      validated cognitive behavioral therapy, called STreSS. The study is designed as a
      randomized controlled trial in which 84 participants are randomly allocated
      between the treatments. Long-term efficacy is investigated through data extracts
      from the national database of Statistics Denmark on the sick leave and the health
      care consumption. The results show that both the NNBT and the STreSS lead to a
      significant decrease in number of contacts with a general practitioner in the
      period from twelve months prior to treatment to twelve months after treatment;
      and, a significant decrease in long-term sick leave from the month prior to
      treatment to twelve months after treatment. The positive long-term effects
      provide validation for the NNBT as an efficient treatment of stress-related
      illnesses.

PMID- 29342953
TI  - Review of Recent Metamaterial Microfluidic Sensors.
AB  - Metamaterial elements/arrays exhibit a sensitive response to fluids yet with a
      small footprint, therefore, they have been an attractive choice to realize
      various sensing devices when integrated with microfluidic technology. Micro
      channels made from inexpensive biocompatible materials avoid any contamination
      from environment and require only microliter-nanoliter sample for sensing. Simple
      design, easy fabrication process, light weight prototype, and instant
      measurements are advantages as compared to conventional (optical, electrochemical
      and biological) sensing systems. Inkjet-printed flexible sensors find their
      utilization in rapidly growing wearable electronics and health-monitoring
      flexible devices. Adequate sensitivity and repeatability of these low profile
      microfluidic sensors make them a potential candidate for point-of-care testing
      which novice patients can use reliably. Aside from degraded sensitivity and lack
      of selectivity in all practical microwave chemical sensors, they require an
      instrument, such as vector network analyzer for measurements and not readily
      available as a self-sustained portable sensor. This review article presents state
      of-the-art metamaterial inspired microfluidic bio/chemical sensors (passive
      devices ranging from gigahertz to terahertz range) with an emphasis on
      metamaterial sensing circuit and microfluidic detection. We also highlight
      challenges and strategies to cope these issues which set future directions.

PMID- 29342954
TI  - A Built-In CpG Adjuvant in RSV F Protein DNA Vaccine Drives a Th1 Polarized and
      Enhanced Protective Immune Response.
AB  - Human respiratory syncytial virus (RSV) is the most significant cause of acute
      lower respiratory infection in children. However, there is no licensed vaccine
      available. Here, we investigated the effect of five or 20 copies of C-Class of
      CpG ODN (CpG-C) motif incorporated into a plasmid DNA vaccine encoding RSV fusion
      (F) glycoprotein on the vaccine-induced immune response. The addition of CpG-C
      motif enhanced serum binding and virus-neutralizing antibody responses in BALB/c
      mice immunized with the DNA vaccines. Moreover, mice vaccinated with CpG-modified
      vaccines, especially with the higher 20 copies, resulted in an enhanced shift
      toward a Th1-biased antibody and T-cell response, a decrease in pulmonary
      pathology and virus replication, and a decrease in weight loss after RSV
      challenge. This study suggests that CpG-C motif, cloned into the backbone of DNA
      vaccine encoding RSV F glycoprotein, functions as a built-in adjuvant capable of
      improving the efficacy of DNA vaccine against RSV infection.

PMID- 29342956
TI  - Development of a Scale-up Tool for Pervaporation Processes.
AB  - In this study, an engineering tool for the design and optimization of
      pervaporation processes is developed based on physico-chemical modelling coupled
      with laboratory/mini-plant experiments. The model incorporates the solution
      diffusion-mechanism, polarization effects (concentration and temperature), axial
      dispersion, pressure drop and the temperature drop in the feed channel due to
      vaporization of the permeating components. The permeance, being the key model
      parameter, was determined via dehydration experiments on a mini-plant scale for
      the binary mixtures ethanol/water and ethyl acetate/water. A second set of
      experimental data was utilized for the validation of the model for two chemical
      systems. The industrially relevant ternary mixture, ethanol/ethyl acetate/water,
      was investigated close to its azeotropic point and compared to a simulation
      conducted with the determined binary permeance data. Experimental and simulation
      data proved to agree very well for the investigated process conditions. In order
      to test the scalability of the developed engineering tool, large-scale data from
      an industrial pervaporation plant used for the dehydration of ethanol was
      compared to a process simulation conducted with the validated physico-chemical
      model. Since the membranes employed in both mini-plant and industrial scale were
      of the same type, the permeance data could be transferred. The comparison of the
      measured and simulated data proved the scalability of the derived model.

PMID- 29342955
TI  - Pharmacokinetics of Schizandrin and Its Pharmaceutical Products Assessed Using a
      Validated LC-MS/MS Method.
AB  - Schisandra chinensis has been used as an important component in various
      prescriptions in traditional Chinese medicine and, more recently, in Western
      based medicine for its anti-hepatotoxic effect. The aim of this study was to
      develop a selective, rapid, and sensitive ultra-performance liquid chromatography
      tandem mass spectrometry method for pharmacokinetic studies of schizandrin in
      rats. Liquid-liquid extraction was used for plasma sample preparation. A UHPLC
      reverse-phase C18e column (100 mm * 2.1 mm, 2 MUm) coupled with a mobile phase of
      methanol-0.1% formic acid (85:15, v/v) was used for sample separation. A triple
      quadrupole tandem mass spectrometer was used to detect the analytes in the
      selected reaction monitoring mode. The linear range of schizandrin in rat plasma
      was 5.0-1000 ng/mL (r2 > 0.999), with a lower limit of quantification of 5 ng/mL.
      The method was validated with regard to accuracy, intra-day and inter-day
      precision, linearity, stability, recovery, and matrix effects in rat plasma,
      which were acceptable according to the biological method validation guidelines
      developed by the FDA. This method was successfully applied to a pharmacokinetic
      study after oral administration of 3 g/kg and 10 g/kg of Schisandra chinensis
      products, which yielded a maximum concentration of schizandrin of 0.08 +/- 0.07
      and 0.15 +/- 0.09 MUg/mL, respectively. A parallel study design was used to
      investigate the oral bioavailability of single compound of schizandrin and the
      herbal extract, the single compound of pure schizandrin (10 mg/kg, i.v.), pure
      schizandrin (10 mg/kg, p.o.), and the herbal extract of Schisandra chinensis (3
      g/kg and 10 g/kg, p.o.) were given individually. The dose of Schisandra chinensis
      (3 g/kg) equivalent to schizandrin (5.2 mg/kg); the dose of Schisandra chinensis
      (10 g/kg) equivalent to schizandrin (17.3 mg/kg). The result demonstrated that
      the oral bioavailability of schizandrin was approximately 15.56 +/- 10.47% in
      rats, however the oral bioavailability of herbal extract was higher than single
      compound. The method was successfully applied to the pharmacokinetic study of
      pure schizandrin after oral administration of its pharmaceutical industry
      products in rats.

PMID- 29342957
TI  - Comparative Transcriptome Analysis Identifies Putative Genes Involved in Steroid
      Biosynthesis in Euphorbia tirucalli.
AB  - Phytochemical analysis of different Euphorbia tirucalli tissues revealed a
      contrasting tissue-specificity for the biosynthesis of euphol and beta
      sitosterol, which represent the two pharmaceutically active steroids in E.
      tirucalli. To uncover the molecular mechanism underlying this tissue-specificity
      for phytochemicals, a comprehensive E. tirucalli transcriptome derived from its
      root, stem, leaf and latex was constructed, and a total of 91,619 unigenes were
      generated with 51.08% being successfully annotated against the non-redundant (Nr)
      protein database. A comparison of the transcriptome from different tissues
      discovered members of unigenes in the upstream steps of sterol backbone
      biosynthesis leading to this tissue-specific sterol biosynthesis. Among them, the
      putative oxidosqualene cyclase (OSC) encoding genes involved in euphol synthesis
      were notably identified, and their expressions were significantly up-regulated in
      the latex. In addition, genome-wide differentially expressed genes (DEGs) in the
      different E. tirucalli tissues were identified. The cluster analysis of those
      DEGs showed a unique expression pattern in the latex compared with other tissues.
      The DEGs identified in this study would enrich the insights of sterol
      biosynthesis and the regulation mechanism of this latex-specificity.

PMID- 29342958
TI  - An Enhanced Method to Estimate Heart Rate from Seismocardiography via Ensemble
      Averaging of Body Movements at Six Degrees of Freedom.
AB  - Continuous cardiac monitoring has been developed to evaluate cardiac activity
      outside of clinical environments due to the advancement of novel instruments.
      Seismocardiography (SCG) is one of the vital components that could develop such a
      monitoring system. Although SCG has been presented with a lower accuracy, this
      novel cardiac indicator has been steadily proposed over traditional methods such
      as electrocardiography (ECG). Thus, it is necessary to develop an enhanced method
      by combining the significant cardiac indicators. In this study, the six-axis
      signals of accelerometer and gyroscope were measured and integrated by the L2
      normalization and multi-dimensional kineticardiography (MKCG) approaches,
      respectively. The waveforms of accelerometer and gyroscope were standardized and
      combined via ensemble averaging, and the heart rate was calculated from the
      dominant frequency. Thirty participants (15 females) were asked to stand or sit
      in relaxed and aroused conditions. Their SCG was measured during the task. As a
      result, proposed method showed higher accuracy than traditional SCG methods in
      all measurement conditions. The three main contributions are as follows: (1) the
      ensemble averaging enhanced heart rate estimation with the benefits of the six
      axis signals; (2) the proposed method was compared with the previous SCG method
      that employs fewer-axis; and (3) the method was tested in various measurement
      conditions for a more practical application.

PMID- 29342960
TI  - A Low-Cost Inkjet-Printed Aptamer-Based Electrochemical Biosensor for the
      Selective Detection of Lysozyme.
AB  - Recently, inkjet-printing has gained increased popularity in applications such as
      flexible electronics and disposable sensors, as well as in wearable sensors
      because of its multifarious advantages. This work presents a novel, low-cost
      immobilization technique using inkjet-printing for the development of an aptamer
      based biosensor for the detection of lysozyme, an important biomarker in various
      disease diagnosis. The strong affinity between the carbon nanotube (CNT) and the
      single-stranded DNA is exploited to immobilize the aptamers onto the working
      electrode by printing the ink containing the dispersion of CNT-aptamer complex.
      The inkjet-printing method enables aptamer density control, as well as high
      resolution patternability. Our developed sensor shows a detection limit of 90
      ng/mL with high target selectivity against other proteins. The sensor also
      demonstrates a shelf-life for a reasonable period. This technology has potential
      for applications in developing low-cost point-of-care diagnostic testing kits for
      home healthcare.

PMID- 29342959
TI  - Structural Insights in Multifunctional Papillomavirus Oncoproteins.
AB  - Since their discovery in the mid-eighties, the main papillomavirus oncoproteins
      E6 and E7 have been recalcitrant to high-resolution structure analysis. However,
      in the last decade a wealth of three-dimensional information has been gained on
      both proteins whether free or complexed to host target proteins. Here, we first
      summarize the diverse activities of these small multifunctional oncoproteins.
      Next, we review the available structural data and the new insights they provide
      about the evolution of E6 and E7, their multiple interactions and their
      functional variability across human papillomavirus (HPV) species.

PMID- 29342961
TI  - Effects of Salt Stress on Plant Growth, Antioxidant Capacity, Glandular Trichome
      Density, and Volatile Exudates of Schizonepeta tenuifolia Briq.
AB  - Salinity is a major abiotic factor affecting plant growth and secondary
      metabolism. However, no information is available about its effects on
      Schizonepeta tenuifolia Briq., a traditional Chinese herb. Here, we investigated
      the changes of plant growth, antioxidant capacity, glandular trichome density,
      and volatile exudates of S. tenuifolia exposed to salt stress (0, 25, 50, 75, 100
      mM NaCl). Results showed that its dry biomass was reduced by salt treatments
      except 25 mM NaCl. Contents of antioxidants, including phenolics and flavonoids,
      increased at low (25 mM) or moderate (50 mM) levels, but declined at severe (75
      and 100 mM) levels. On leaf surfaces, big peltate and small capitate glandular
      trichomes (GTs) were found. Salt treatments, especially at moderate and severe
      concentrations, enhanced the density of total GTs on both leaf sides. The most
      abundant compound in GT volatile exudates was pulegone. Under salinity, relative
      contents of this component and other monoterpenes decreased significantly;
      biosynthesis and accumulation of esters were enhanced, particularly sulfurous
      acid,2-ethylhexyl hexyl ester, which became the second major compound as salinity
      increased. In conclusion, salt stress significantly influenced the growth and
      secondary metabolism of S. tenuifolia, enabling us to study the changes of its
      pharmacological activities.

PMID- 29342963
TI  - Sum of the Magnitude for Hard Decision Decoding Algorithm Based on Loop Update
      Detection.
AB  - In order to improve the performance of non-binary low-density parity check codes
      (LDPC) hard decision decoding algorithm and to reduce the complexity of decoding,
      a sum of the magnitude for hard decision decoding algorithm based on loop update
      detection is proposed. This will also ensure the reliability, stability and high
      transmission rate of 5G mobile communication. The algorithm is based on the hard
      decision decoding algorithm (HDA) and uses the soft information from the channel
      to calculate the reliability, while the sum of the variable nodes' (VN) magnitude
      is excluded for computing the reliability of the parity checks. At the same time,
      the reliability information of the variable node is considered and the loop
      update detection algorithm is introduced. The bit corresponding to the error code
      word is flipped multiple times, before this is searched in the order of most
      likely error probability to finally find the correct code word. Simulation
      results show that the performance of one of the improved schemes is better than
      the weighted symbol flipping (WSF) algorithm under different hexadecimal numbers
      by about 2.2 dB and 2.35 dB at the bit error rate (BER) of 10-5 over an additive
      white Gaussian noise (AWGN) channel, respectively. Furthermore, the average
      number of decoding iterations is significantly reduced.

PMID- 29342962
TI  - Functional Analyses of RUNX3 and CaMKIINalpha in Ovarian Cancer Cell Lines Reveal
      Tumor-Suppressive Functions for CaMKIINalpha and Dichotomous Roles for RUNX3
      Transcript Variants.
AB  - (1) Background: Epithelial ovarian cancer (EOC) is the most lethal cancer of the
      female reproductive system. In an earlier study, we identified multiple genes as
      hypermethylated in tumors of patients with poor prognosis. The most promising
      combination of markers to predict a patient's outcome was CaMKIINalpha and RUNX3.
      Aim of this study was to functionally validate the importance of both genes. (2)
      Methods: IC50 measurements, cell cycle distribution-, proliferation, and
      migration experiments were conducted after transgene overexpression in two EOC
      cell lines. (3) Results: We showed that CaMKIINalpha has tumor suppressive
      functions in vitro and reduces proliferation, migration, and colony formation.
      However, it had no effect on the reversion of the resistance to cisplatin. RUNX3
      exhibited dualistic functions related to cisplatin sensitivity and migration
      capacity, depending on the respective transcript variant (TV). A2780 cells
      expressing RUNX3 TV2-the promoter of which harbors a CpG (5'-C-phosphate-G-3')
      island and is potentially inactivated by hypermethylation-exhibited increased
      cisplatin sensitivity and reduced migration properties. However, RUNX3 TV1, not
      affected by CpG island methylation could be characterized as mediating resistance
      and enhancing migration in A2780. The higher resistance of RUNX3 TV1 transfected
      cells correlates with a reduction of cell proliferation. Moreover, RUNX3 TV1
      expressing cells exhibit a reduced cell cycle arrest at the gap-2 or mitosis
      phase (G2/M) under cisplatin treatment comparable to resistant A2780 subcultures.
      (4) Conclusion: It appears that CaMKIINalpha and RUNX3 TV2 can reduce the
      malignant potential of EOC cells.

PMID- 29342964
TI  - Data-Driven Modeling and Rendering of Force Responses from Elastic Tool
      Deformation.
AB  - This article presents a new data-driven model design for rendering force
      responses from elastic tool deformation. The new design incorporates a six
      dimensional input describing the initial position of the contact, as well as the
      state of the tool deformation. The input-output relationship of the model was
      represented by a radial basis functions network, which was optimized based on
      training data collected from real tool-surface contact. Since the input space of
      the model is represented in the local coordinate system of a tool, the model is
      independent of recording and rendering devices and can be easily deployed to an
      existing simulator. The model also supports complex interactions, such as self
      and multi-contact collisions. In order to assess the proposed data-driven model,
      we built a custom data acquisition setup and developed a proof-of-concept
      rendering simulator. The simulator was evaluated through numerical and
      psychophysical experiments with four different real tools. The numerical
      evaluation demonstrated the perceptual soundness of the proposed model, meanwhile
      the user study revealed the force feedback of the proposed simulator to be
      realistic.

PMID- 29342965
TI  - Lipid-Based Nanoparticles as a Potential Delivery Approach in the Treatment of
      Rheumatoid Arthritis.
AB  - Rheumatoid arthritis (RA), a chronic and joint-related autoimmune disease,
      results in immune dysfunction and destruction of joints and cartilages. Small
      molecules and biological therapies have been applied in a wide variety of
      inflammatory disorders, but their utility as a therapeutic agent is limited by
      poor absorption, rapid metabolism, and serious side effects. To improve these
      limitations, nanoparticles, which are capable of encapsulating and protecting
      drugs from degradation before they reach the target site in vivo, may serve as
      drug delivery systems. The present research proposes a platform for different
      lipid nanoparticle approaches for RA therapy, taking advantage of the newly
      emerging field of lipid nanoparticles to develop a targeted theranostic system
      for application in the treatment of RA. This review aims to present the recent
      major application of lipid nanoparticles that provide a biocompatible and
      biodegradable delivery system to effectively improve RA targeting over free drugs
      via the presentation of tissue-specific targeting of ligand-controlled drug
      release by modulating nanoparticle composition.

PMID- 29342966
TI  - Fabrication of a Textile-Based Wearable Blood Leakage Sensor Using Screen-Offset
      Printing.
AB  - We fabricate a wearable blood leakage sensor on a cotton textile by combining two
      newly developed techniques. First, we employ a screen-offset printing technique
      that avoids blurring, short circuiting between adjacent conductive patterns, and
      electrode fracturing to form an interdigitated electrode structure for the sensor
      on a textile. Furthermore, we develop a scheme to distinguish blood from other
      substances by utilizing the specific dielectric dispersion of blood observed in
      the sub-megahertz frequency range. The sensor can detect blood volumes as low as
      15 MUL, which is significantly lower than those of commercially available
      products (which can detect approximately 1 mL of blood) and comparable to a
      recently reported value of approximately 10 MUL. In this study, we merge two
      technologies to develop a more practical skin-friendly sensor that can be applied
      for safe, stress-free blood leakage monitoring during hemodialysis.

PMID- 29342968
TI  - A Fast and Robust Extrinsic Calibration for RGB-D Camera Networks.
AB  - From object tracking to 3D reconstruction, RGB-Depth (RGB-D) camera networks play
      an increasingly important role in many vision and graphics applications.
      Practical applications often use sparsely-placed cameras to maximize visibility,
      while using as few cameras as possible to minimize cost. In general, it is
      challenging to calibrate sparse camera networks due to the lack of shared scene
      features across different camera views. In this paper, we propose a novel
      algorithm that can accurately and rapidly calibrate the geometric relationships
      across an arbitrary number of RGB-D cameras on a network. Our work has a number
      of novel features. First, to cope with the wide separation between different
      cameras, we establish view correspondences by using a spherical calibration
      object. We show that this approach outperforms other techniques based on planar
      calibration objects. Second, instead of modeling camera extrinsic calibration
      using rigid transformation, which is optimal only for pinhole cameras, we
      systematically test different view transformation functions including rigid
      transformation, polynomial transformation and manifold regression to determine
      the most robust mapping that generalizes well to unseen data. Third, we
      reformulate the celebrated bundle adjustment procedure to minimize the global 3D
      reprojection error so as to fine-tune the initial estimates. Finally, our
      scalable client-server architecture is computationally efficient: the calibration
      of a five-camera system, including data capture, can be done in minutes using
      only commodity PCs. Our proposed framework is compared with other state-of-the
      arts systems using both quantitative measurements and visual alignment results of
      the merged point clouds.

PMID- 29342969
TI  - Feature Fusion of ICP-AES, UV-Vis and FT-MIR for Origin Traceability of Boletus
      edulis Mushrooms in Combination with Chemometrics.
AB  - Origin traceability is an important step to control the nutritional and
      pharmacological quality of food products. Boletus edulis mushroom is a well-known
      food resource in the world. Its nutritional and medicinal properties are
      drastically varied depending on geographical origins. In this study, three sensor
      systems (inductively coupled plasma atomic emission spectrophotometer (ICP-AES),
      ultraviolet-visible (UV-Vis) and Fourier transform mid-infrared spectroscopy (FT
      MIR)) were applied for the origin traceability of 192 mushroom samples (caps and
      stipes) in combination with chemometrics. The difference between cap and stipe
      was clearly illustrated based on a single sensor technique, respectively. Feature
      variables from three instruments were used for origin traceability. Two
      supervised classification methods, partial least square discriminant analysis
      (FLS-DA) and grid search support vector machine (GS-SVM), were applied to develop
      mathematical models. Two steps (internal cross-validation and external prediction
      for unknown samples) were used to evaluate the performance of a classification
      model. The result is satisfactory with high accuracies ranging from 90.625% to
      100%. These models also have an excellent generalization ability with the optimal
      parameters. Based on the combination of three sensory systems, our study provides
      a multi-sensory and comprehensive origin traceability of B. edulis mushrooms.

PMID- 29342967
TI  - Structural Diversity and Biological Activities of Cyclic Depsipeptides from
      Fungi.
AB  - Cyclic depsipeptides (CDPs) are cyclopeptides in which amide groups are replaced
      by corresponding lactone bonds due to the presence of a hydroxylated carboxylic
      acid in the peptide structure. These peptides sometimes display additional
      chemical modifications, including unusual amino acid residues in their
      structures. This review highlights the occurrence, structures and biological
      activities of the fungal CDPs reported until October 2017. About 352 fungal CDPs
      belonging to the groups of cyclic tri-, tetra-, penta-, hexa-, hepta-, octa-,
      nona-, deca-, and tridecadepsipeptides have been isolated from fungi. These
      metabolites are mainly reported from the genera Acremonium, Alternaria,
      Aspergillus, Beauveria, Fusarium, Isaria, Metarhizium, Penicillium, and
      Rosellina. They are known to exhibit various biological activities such as
      cytotoxic, phytotoxic, antimicrobial, antiviral, anthelmintic, insecticidal,
      antimalarial, antitumoral and enzyme-inhibitory activities. Some CDPs (i.e.,
      PF1022A, enniatins and destruxins) have been applied as pharmaceuticals and
      agrochemicals.

PMID- 29342971
TI  - Walking Distance Estimation Using Walking Canes with Inertial Sensors.
AB  - A walking distance estimation algorithm for cane users is proposed using an
      inertial sensor unit attached to various positions on the cane. A standard
      inertial navigation algorithm using an indirect Kalman filter was applied to
      update the velocity and position of the cane during movement. For quadripod
      canes, a standard zero-velocity measurement-updating method is proposed. For
      standard canes, a velocity-updating method based on an inverted pendulum model is
      proposed. The proposed algorithms were verified by three walking experiments with
      two different types of canes and different positions of the sensor module.

PMID- 29342970
TI  - The Possible Importance of beta3 Integrins for Leukemogenesis and Chemoresistance
      in Acute Myeloid Leukemia.
AB  - Acute myeloid leukemia (AML) is an aggressive bone marrow malignancy where the
      immature leukemia cells communicate with neighboring cells through constitutive
      cytokine release and through their cell surface adhesion molecules. The primary
      AML cells express various integrins. These heterodimeric molecules containing an
      alpha and a beta chain are cell surface molecules that bind extracellular matrix
      molecules, cell surface molecules and soluble mediators. The beta3 integrin
      (ITGB3) chain can form heterodimers only with the two alpha chains alphaIIb and
      alphaV. These integrins are among the most promiscuous and bind to a large number
      of ligands, including extracellular matrix molecules, cell surface molecules and
      soluble mediators. Recent studies suggest that the two beta3 integrins are
      important for leukemogenesis and chemosensitivity in human AML. Firstly, alphaIIb
      and beta3 are both important for adhesion of AML cells to vitronectin and
      fibronectin. Secondly, beta3 is important for the development of murine AML and
      also for the homing and maintenance of the proliferation for xenografted primary
      human AML cells, and for maintaining a stem cell transcriptional program. These
      last effects seem to be mediated through Syk kinase. The beta3 expression seems
      to be regulated by HomeboxA9 (HoxA9) and HoxA10, and the increased beta3
      expression then activates spleen tyrosine kinase (Syk) and thereby contributes to
      cytokine hypersensitivity and activation of beta2 integrins. Finally, high
      integrin alphaV/beta3 expression is associated with an adverse prognosis in AML
      and decreased sensitivity to the kinase inhibitor sorafenib; this integrin can
      also be essential for osteopontin-induced sorafenib resistance in AML. In the
      present article, we review the experimental and clinical evidence for a role of
      beta3 integrins for leukemogenesis and chemosensitivity in AML.

PMID- 29342973
TI  - Biogenic Weathering: Solubilization of Iron from Minerals by Epilithic Freshwater
      Algae and Cyanobacteria.
AB  - A sandstone outcrop exposed to freshwater seepage supports a diverse assemblage
      of photosynthetic microbes. Dominant taxa are two cyanophytes (Oscillatoria sp.,
      Rivularia sp.) and a unicellular green alga (Palmellococcus sp.). Less abundant
      taxa include a filamentous green alga, Microspora, and the desmid Cosmarium.
      Biologic activity is evidenced by measured levels of chlorophyll and lipids.
      Bioassay methods confirm the ability of these microbes to dissolve and metabolize
      Fe from ferruginous minerals. Chromatographic analysis reveals citric acid as the
      likely chelating agent; this low molecular weight organic acid is detectable in
      interstitial fluid in the sandstone, measured as 0.0756 mg/mL. Bioassays using a
      model organism, Synechoccus elongates strain UTEX 650, show that Fe availability
      varies among different ferruginous minerals. In decreasing order of Fe
      availability: magnetite > limonite > biotite > siderite > hematite. Biotite was
      selected for detailed study because it is the most abundant iron-bearing mineral
      in the sandstone. SEM images support the microbiologic evidence, showing
      weathering of biotite compared to relatively undamaged grains of other silicate
      minerals.

PMID- 29342972
TI  - The Effect of Combining Natural Terpenes and Antituberculous Agents against
      Reference and Clinical Mycobacterium tuberculosis Strains.
AB  - Background: On account of emergence of multi- and extensively drug-resistant
      Mycobacterium tuberculosis (Mtb) strains, combinations of drugs with natural
      compounds were tested to search for antibiotic activity enhancers. In this work
      we studied terpenes (alpha-pinene, bisabolol, beta-elemene, (R)-limonene, (S)
      limonene, myrcene, sabinene), which are the main constituents of essential oil
      obtained from Mutellina purpurea L., a plant with described antitubercular
      activity, to investigate their interactions with antibiotics against reference
      Mtb strains and multidrug-resistant clinical isolates. Methods: The serial
      dilution method was used to evaluate the minimal inhibitory concentration (MIC)
      of tested compounds, while the fractional inhibitory concentration index (FICI)
      was calculated for characterization of interactions. Moreover, IC50 values of
      tested compounds were determined using monkey kidney epithelial cell line (GMK).
      Results: The combinations of all studied terpenes with ethambutol or rifampicin
      resulted in a synergistic interaction. Bisabolol and (R)-limonene decreased the
      MIC for rifampicin at least two-fold for all tested strains, however no
      synergistic action was observed against virulent strains. The tested terpenes
      showed slight (bisabolol) or no cytotoxic effect against normal eukaryotic cells
      in vitro. Conclusions: The obtained enhanced activity (FICI < 0.5) of ethambutol
      and rifampicin against H37Ra strain under the influence of the studied terpenes
      may be correlated to the capability of essential oil constituents to modify
      bacterial resistance mechanisms in general. The observed differences in avirulent
      and virulent bacteria susceptibility to terpenes tested separately and in
      combinations with antibiotics can be correlated with the differences in the cell
      wall structure between H37Ra mutant and all virulent strains.

PMID- 29342974
TI  - Trypsin Binding with Copper Ions Scavenges Superoxide: Molecular Dynamics-Based
      Mechanism Investigation.
AB  - Trypsin is a serine protease, which has been proved to be a novel superoxide
      scavenger. The burst of superoxide induced by polychlorinated biphenyls can be
      impeded by trypsin in both wild type and sod knockout mutants of Escherichia
      coli. The experimental results demonstrated that the activities of superoxide
      scavenging of trypsin were significantly accelerated by Cu ions. Also, with the
      addition of Cu ions, a new beta-sheet (beta7) transited from a random coil in the
      Cu(II)-trypsin (TP) system, which was favorable for the formation of more
      contacts with other sheets of trypsin. Residue-residue network analysis and the
      porcupine plots proved that the Cu ion in trypsin strengthened some native
      interactions among residues, which ultimately resulted in much greater stability
      of the Cu(II)-TP system. Moreover, compact and stable trypsin structures with Cu
      ions might be responsible for significantly provoking the activity of superoxide
      scavenging.

PMID- 29342975
TI  - Gallic Acid Alleviates Hypertriglyceridemia and Fat Accumulation via Modulating
      Glycolysis and Lipolysis Pathways in Perirenal Adipose Tissues of Rats Fed a High
      Fructose Diet.
AB  - This study investigated the ameliorative effect of gallic acid (GA) on
      hypertriglyceridemia and fat accumulation in perirenal adipose tissues of high
      fructose diet (HFD)-induced diabetic rats. The previous results showed that
      orally administered GA (30 mg/kg body weight) for four weeks significantly
      reduced the levels of plasma glucose and triglyceride (TG) in HFD rats. GA also
      markedly decreased the perirenal adipose tissues weight of HFD rats in present
      study (p < 0.05). Western blot assay indicated that GA restored expression of
      insulin signaling-related proteins, such as insulin receptor (IR), protein kinase
      C-zeta (PKC-zeta), and glucose transporter-4 (GLUT4) in the perirenal adipose
      tissues of HFD rats. Moreover, GA enhanced expression of glycolysis-related
      proteins, such as phosphofructokinase (PFK) and pyruvate kinase (PK), and
      increased the expression of lipolysis-related proteins, such as adipose
      triglyceride lipase (ATGL), which is involved in lipolysis in the perirenal
      adipose tissues of HFD rats. This study revealed that GA may alleviate
      hypertriglyceridemia and fat accumulation through enhancing glycolysis and
      lipolysis pathways in perirenal adipose tissues of HFD rats. These findings also
      suggest the potential of GA in preventing the progression of diabetes mellitus
      (DM) complications.

PMID- 29342976
TI  - A Child's Concept of Pain: An International Survey of Pediatric Pain Experts.
AB  - A child's 'concept of pain' refers to how they understand what pain actually is,
      what function pain serves, and what biological processes are thought to underpin
      it. We aimed to determine pediatric pain experts' opinions of: (1) the importance
      and usefulness of assessing a child's concept of pain in clinical and/or research
      settings; (2) the usefulness of the content of items within currently published
      adult-targeted resources for assessing a child's concept of pain; and (3)
      important domains of a child's concept of pain to assess. Forty-nine pediatric
      pain experts (response rate = 75.4%) completed an online survey. Descriptive
      statistics and frequency of responses were analyzed. Experts from all included
      disciplines reported that assessing a child's concept of pain is important and
      useful both clinically and in a research setting (>80% reported very or extremely
      useful for each item). Experts considered that the content of 13 items from
      currently published adult-targeted resources was useful, but the wording was too
      complex for children aged 8-12 years. Experts considered that all seven of the
      proposed domains of a child's concept of pain was important to assess. The
      findings can be used to inform the development of an assessment tool for a
      child's concept of pain.

PMID- 29342977
TI  - Correction: Dierking, Ingo and Al-Zangana, Shakhawan. Lyotropic Liquid Crystal
      Phases from Anisotropic Nanomaterials. Nanomaterials 2017, 7, 305.
AB  - Due to an oversight during production, the authors wish to make the following
      correction to reference [65] of this paper [...].

PMID- 29342979
TI  - Catalysts on Formation of Carbon-Encapsulated Iron Nanoparticles from Kraft
      Lignin.
AB  - Effects of physical and chemical states of iron-based catalysts on the formation
      of carbon-encapsulated iron nanoparticles (CEINs) synthesized thermally from
      kraft lignin were investigated. Experimental results indicated that if solution
      based iron nitrate (FeN) was used as an iron source for the catalyst, CEINs
      observed were alpha-Fe and gamma-Fe-based cores encapsulated by few layers
      graphitic-carbon (mostly 1-5 layers) and the majority of these CEINs were
      embedded in amorphous carbon matrix. The formation of graphitic-carbon shells is
      believed based on the dissolution and precipitation mechanism of amorphous carbon
      acting as the carbon source. If solid-based iron nanoparticles (FePs) were used
      as the catalyst, CEINs observed were alpha-Fe, gamma-Fe, and Fe3C-based cores
      encapsulated with tangled graphitic-carbon nanoribbons and carbon tubules and the
      majority of these CEINs were found along the edge of amorphous carbon matrix. The
      growth of tangled graphitic-carbon nanoribbons and carbon tubules is based on a
      chemical vapor decomposition process, i.e., the carbonaceous gases from kraft
      lignin decomposition served as the carbon source.

PMID- 29342978
TI  - Host-Guest Interaction of Cucurbit[8]uril with N-(3-Aminopropyl)cyclohexylamine:
      Cyclohexyl Encapsulation Triggered Ternary Complex.
AB  - The host-guest interaction of a series of cyclohexyl-appended guests with
      cucurbit[8]uril (Q[8]) was studied by 1H NMR spectroscopy, isothermal titration
      calorimetry (ITC), and X-ray crystallography. The X-ray structure revealed that
      two cycloalkane moieties can be simultaneously encapsulated in the hydrophobic
      cavity of the Q[8] host to form a ternary complex for the first time.

PMID- 29342980
TI  - Dietary Intake of Flavonoids and Ventilatory Function in European Adults: A
      GA2LEN Study.
AB  - BACKGROUND: Flavonoids exert anti-inflammatory properties and modulate oxidative
      stress in vitro, suggesting a protective effect on lung function, but
      epidemiological studies examining this association are scarce. METHODS: A
      stratified random sample was drawn from the GA2LEN screening survey, in which
      55,000 adults aged 15 to 75 answered a questionnaire on respiratory symptoms.
      Post-bronchodilator spirometry was obtained from 2850 subjects. Forced vital
      capacity (FVC), the ratio between the forced exhaled volume in 1 second (FEV1)
      and FVC (FEV1/FVC), FVC below lower limit of normal (FVC < LLN), and FEV1/FVC <
      LLN were calculated. Intake of the six main subclasses of flavonoids was
      estimated using the GA2LEN Food Frequency Questionnaire. Adjusted associations
      between outcomes and each subclass of flavonoids were examined with multivariate
      regressions. Simes' procedure was used to test for multiple comparisons. RESULTS:
      A total of 2599 subjects had valid lung function and dietary data. A lower
      prevalence of FVC < LLN (airway restriction) was observed in those with higher
      total flavonoid (adjusted odds ratio (aOR), higher vs. lowest quintile intake
      0.58; 95% Confidence Interval (CI) 0.36, 0.94), and pro-anthocyanidin intakes
      (aOR 0.47; 95% CI 0.27, 0.81). A higher FEV1/FVC was associated with higher
      intakes of total flavonoids and pro-anthocyanidins (adjusted correlation
      coefficient (a beta-coeff 0.33; 0.10, 0.57 and a beta-coeff 0.44; 95% CI 0.19,
      0.69, respectively). After Simes' procedure, the statistical significance of each
      of these associations was attenuated but remained below 0.05, with the exception
      of total flavonoids and airway restriction. CONCLUSIONS: This population-based
      study in European adults provides cross-sectional evidence of a positive
      association of total flavonoid intake and pro-anthocyanidins and ventilatory
      function, and a negative association with spirometric restriction in European
      adults.

PMID- 29342981
TI  - Current Evidence on Vitamin D Deficiency and Metabolic Syndrome in Obese
      Children: What Does the Evidence from Saudi Arabia Tell Us?
AB  - Obesity and vitamin D deficiency represent major health problems among Saudi
      children, and have been linked to chronic diseases. Obese children are at risk of
      developing vitamin D deficiency, which appears to have negative influences on
      energy homeostasis, impeded bone mineralisation, insulin resistance and
      inflammation. Evidence supporting the association between vitamin D deficiency of
      obese children and metabolic syndrome has not specifically been studied in early
      childhood. The mechanisms through which vitamin D deficiency is associated with
      metabolic syndrome in obese children needs further elucidation. This commentary
      aims to (i) summarise current knowledge of the association between vitamin D
      deficiency and metabolic syndrome in obese children; and (ii) discuss current
      evidence for the association among Saudi Arabian children.

PMID- 29342982
TI  - Detection of ZrO2 Nanoparticles in Lung Tissue Sections by Time-of-Flight
      Secondary Ion Mass Spectrometry and Ion Beam Microscopy.
AB  - The increasing use of nanoparticles (NP) in commercial products requires
      elaborated techniques to detect NP in the tissue of exposed organisms. However,
      due to the low amount of material, the detection and exact localization of NP
      within tissue sections is demanding. In this respect, Time-of-Flight Secondary
      Ion Mass Spectrometry (ToF-SIMS) and Ion Beam Microscopy (IBM) are promising
      techniques, because they both offer sub-micron lateral resolutions along with
      high sensitivities. Here, we compare the performance of the non-material
      consumptive IBM and material-consumptive ToF-SIMS for the detection of ZrO2 NP
      (primary size 9-10 nm) in rat lung tissue. Unfixed or methanol-fixed air-dried
      cryo-sections were subjected to IBM using proton beam scanning or to three
      dimensional ToF-SIMS (3D ToF-SIMS) using either oxygen or argon gas cluster ion
      beams for complete sample sputtering. Some sample sites were analyzed first by
      IBM and subsequently by 3D ToF-SIMS, to compare results from exactly the same
      site. Both techniques revealed that ZrO2 NP particles occurred mostly
      agglomerated in phagocytic cells with only small quantities being associated to
      the lung epithelium, with Zr, S, and P colocalized within the same biological
      structures. However, while IBM provided quantitative information on element
      distribution, 3D ToF-SIMS delivered a higher lateral resolution and a lower limit
      of detection under these conditions. We, therefore, conclude that 3D ToF-SIMS,
      although not yet a quantitative technique, is a highly valuable tool for the
      detection of NP in biological tissue.

PMID- 29342983
TI  - Assessing the Perceptions and Practice of Self-Medication among Bangladeshi
      Undergraduate Pharmacy Students.
AB  - Objectives: To evaluate the perceptions and extent of practicing self-medication
      among undergraduate pharmacy students. Methods: This cross-sectional,
      questionnaire-based study was conducted over a six month period (January to June
      2016) among undergraduate pharmacy students in five reputable public universities
      of Bangladesh. It involved face-to-face interviews regarding self-medication of
      250 respondents selected by simple random sampling. Results: Self-medication was
      reported by 88.0% of students. Antipyretics (58.40%) were mostly preferred for
      the treatment of fever and headaches. The major cause for self-medication was
      minor illness (59.60%, p = 0.73) while previous prescriptions were the main
      source of knowledge as well as the major factor (52.80%, p = 0.94) dominating the
      self-medication practice. The results also demonstrated 88.80% of students had
      previous knowledge on self-medication and 83.60% of students always checked the
      information on the label; mainly the expiry date before use (85.60%). A
      significant (p < 0.05) portion of the students (51% male and 43% female)
      perceived it was an acceptable practice as they considered self-medication to be
      a segment of self-care. Furthermore, students demonstrated differences in their
      response level towards the adverse effect of drugs, the health hazard by a higher
      dose of drug, a physician's help in case of side effects, taking medicine without
      proper knowledge, and stopping selling medicine without prescription.
      Conclusions: Self-medication was commonly used among pharmacy students primarily
      for minor illnesses using over-the-counter medications. Although it is an
      inevitable practice for them it should be considered an important public health
      problem as this practice may increase the misuse or irrational use of medicines.

PMID- 29342984
TI  - Amaranthus caudatus Stimulates Insulin Secretion in Goto-Kakizaki Rats, a Model
      of Diabetes Mellitus Type 2.
AB  - Diabetes Mellitus Type 2 prevalence is increasing worldwide; thus efforts to
      develop novel therapeutic strategies are required. Amaranthus caudatus (AC) is a
      pseudo-cereal with reported anti-diabetic effects that is usually consumed in
      food preparations in Bolivia. This study evaluated the anti-diabetic
      nutraceutical property of an AC hydroethanolic extract that contains mainly
      sugars and traces of polyphenols and amino acids (as shown by nalysis with liquid
      chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR)),
      in type 2 diabetic Goto-Kakizaki (GK) rats and healthy Wistar (W) rats. A single
      oral administration of AC extract (2000 mg/kg body weight) improved glucose
      tolerance during Oral Glucose Tolerance Tests (OGTT) in both GK rats and in W
      rats. Long-term treatment (21 days) with AC (1000 mg/kg b.w.) improved the
      glucose tolerance evaluated by the area under the curve (AUC) of glucose levels
      during the OGTT, in both GK and W rats. The HbA1c levels were reduced in both GK
      (19.83%) and W rats (10.7%). This effect was secondary to an increase in serum
      insulin levels in both GK and W rats and confirmed in pancreatic islets, isolated
      from treated animals, where the chronic AC exposure increased the insulin
      production 4.1-fold in GK and 3.7-fold in W rat islets. Furthermore, the effect
      of AC on in vitro glucose-dependent insulin secretion (16.7 mM glucose) was
      concentration-dependent up to 50 mg/mL, with 8.5-fold increase in GK and 5.7-fold
      in W rat islets, and the insulin secretion in perifused GK and W rat islets
      increased 31 and nine times, respectively. The mechanism of action of AC on
      insulin secretion was shown to involve calcium, PKA and PKC activation, and G
      protein coupled-exocytosis since the AC effect was reduced 38% by nifedipine (L
      type channel inhibitor), 77% by H89 (PKA inhibitor), 79% by Calphostine-C (PKC
      inhibitor) and 20% by pertussis toxin (G-protein suppressor).

PMID- 29342985
TI  - Community-Based Health and Exposure Study around Urban Oil Developments in South
      Los Angeles.
AB  - Oilfield-adjacent communities often report symptoms such as headaches and/or
      asthma. Yet, little data exists on health experiences and exposures in urban
      environments with oil and gas development. In partnership with Promotoras de
      Salud (community health workers), we gathered household surveys nearby two oil
      production sites in Los Angeles. We tested the capacity of low-cost sensors for
      localized exposure estimates. Bilingual surveys of 205 randomly sampled
      residences were collected within two 1500 ft. buffer areas (West Adams and
      University Park) surrounding oil development sites. We used a one-sample
      proportion test, comparing overall rates from the California Health Interview
      Survey (CHIS) of Service Planning Area 6 (SPA6) and Los Angeles County for
      variables of interest such as asthma. Field calibrated low-cost sensors recorded
      methane emissions. Physician diagnosed asthma rates were reported to be higher
      within both buffers than in SPA6 or LA County. Asthma prevalence in West Adams
      but not University Park was significantly higher than in Los Angeles County.
      Respondents with diagnosed asthma reported rates of emergency room visits in the
      previous 12 months similar to SPA6. 45% of respondents were unaware of oil
      development; 63% of residents would not know how to contact local regulatory
      authorities. Residents often seek information about their health and site-related
      activities. Low-cost sensors may be useful in highlighting differences between
      sites or recording larger emission events and can provide localized data
      alongside resident-reported symptoms. Regulatory officials should help clarify
      information to the community on methods for reporting health symptoms. Our
      community-based participatory research (CBPR) partnership supports efforts to
      answer community questions as residents seek a safety buffer between sensitive
      land uses and active oil development.

PMID- 29342986
TI  - Regioselectivity in Reactions between Bis(2-benzothiazolyl)ketone and Vinyl
      Grignard Reagents: C- versus O-alkylation-Part III.
AB  - The reaction between bis(2-benzothiazolyl)ketone and vinyl Grignard reagents
      bearing different substituents on the vinyl moiety gave the product derived from
      attack on the carbonylic carbon- and/or oxygen-atom. The regioselectivity of the
      attack depends on the kind of substituents bound to the vinylic carbon atoms and
      on their relative position. The reaction between vinylmagnesium bromide and 2
      methyl-1-propenylmagnesium bromide was carried out under different experimental
      conditions and in the presence of radical scavengers. The results indicate a
      plausible mechanistic pathway involving radical intermediates in the case of O
      alkylation, but a polar ones in the case of classic C-alkylation. This agrees
      with our previous reports indicating a key role played by the delocalization
      ability of the substituents bound to the carbonyl group in driving the
      regioselectivity of the vinylmagnesium bromide attack towards O-alkylation.
      Further support of this was obtained by diffractometric analysis of four distinct
      bis(heteroaryl)ketones.

PMID- 29342987
TI  - [Innovation is an inexhaustible driving force for the disciplinary development].

PMID- 29342988
TI  - [Further improve the level of clinical study and management of pediatric
      cardiovascular diseases in China].

PMID- 29342989
TI  - [Expert consensus on the treatment of vasovagal syncope and postural tachycardia
      syndrome in children].

PMID- 29342990
TI  - [Intensive reading and interpretation of the expert consensus on the treatment of
      vasovagal syncope and postural tachycardia syndrome in children].

PMID- 29342991
TI  - [An analysis of clinical characteristics and acute treatment of supraventricular
      tachycardia in children from a multicenter study].
AB  - Objective: The study assessed the clinical characteristics and response to acute
      intravenous antiarrhythmic drug therapy of supraventricular tachycardia (SVT) in
      children. Methods: This was a multicenter prospective descriptive study including
      257 children from First Hospital of Tsinghua University, Peking University First
      Hospital, Children's Hospital Affiliated to Capital Institute of Pediatrics and
      Beijing Anzhen Hospital who received intravenous antiarrhythmic drug therapy for
      SVT from July 2014 to February 2017. The clinical and tachycardia features,
      response to intravenous antiarrhythmic drug therapy of these children were
      characterized. Statistical analyses were performed using t test, Mann-Whitney U
      test, chi(2) test and H test. Results: The onset of SVT occurred at any age with
      a distribution with positive skewness, 57.6% (n=148) children<1 year, 17.5%
      (n=45) children1~<3 years, 10.5% (n=27) children 3~<6 years and 14.4% (n=37)
      children >= 6 years of age. The percentages of SVT types were 49.4% (n=127) for
      atrioventricular reentry tachycardia (AVRT), 4.3% (n=11) for atrioventricular
      nodal reentry tachycardia (AVNRT), 26.8% (n=69) for unclassified paroxysmal SVT
      and 19.5% (n=50) for atrial tachycardia (AT), respectively. Tachycardia-induced
      cardionyopathy (TIC) secondary to SVT developed in 30 of 225 (13.3%). Left
      ventricular ejection fraction (LVEF) of the 27 children attacked by TIC returned
      to normal after successful control of SVT (41.1%+/-6.3% vs. 60.3%+/-9.2%, t=
      10.397, P=0.000). Complete termination of SVT by antiarrhythmic drugs was
      achieved in 164 of 257 (63.8%), partial termination rate was 18.7% (48 of 257)
      and failure to terminate rate was 17.5% (45 of 257). Propafenone (complete
      cardioversion in 98 (73.1%) of 134) and amiodarone (complete cardioversion in 23
      (76.7%) of 30) showed better efficacy for SVT termination than adenosine
      (complete cardioversion in 26 (44.1%) 59) (chi(2)=20.524, P=0.000). Paroxysmal
      SVT had a higher termination rate on pharmacological therapy than AT (67.1% vs.
      50.0%, chi(2)=6.337, P=0.042). Patients of different age groups had significantly
      different response to antiarrhythmic therapy (chi(2)=13.904, P=0.031). Children<1
      year of age showed the least response to antiarrhythmic drug therapy with
      complete termination in 51 (55.4%) of 92. Adverse effects occurred in 9 patients
      (3.5%): Four patients had severe hypotensive shock using propafenone (n=3) and
      adenosine (n=1), and 3 patients had sinus arrest using adenosine. Conclusion:
      Most (57.6%) children with SVT have their first clinical episode within 1 year of
      age, and AVRT is the most common type. TIC occurs in 13.3% of children with SVT.
      Intravenous antiarrhythmic drug therapy has a 63.8% complete termination rate for
      children with SVT and incidence of adverse effects is 3.5%. Propafenone and
      amiodarone are more effective for SVT termination in children than adenosine.
      Serious adverse effects may occur when using propafenone.

PMID- 29342992
TI  - [Radiofrequency catheter ablation of premature ventricular contractions in
      children under CARTO3 system: a retrospective study from one single center].
AB  - Objective: To evaluate the clinical effect and summarize the experience of
      radiofrequency catheter ablation (RFCA) for children suffered from premature
      ventricular contractions (PVCs). Methods: This retrospective study was conducted
      by descriptive analysis. A total of 108 cases with frequent PVCs from Shanghai
      Children's Medical Center were treated with RFCA under the guidance of CARTO3
      system from January 2011 to December 2016. The immediate success rate of the
      procedure, the recurrence rate and the perioperative complications were
      summarized. The constituent ratio of different PVCs origins, the trend of overall
      procedure time and success rate in recent years were analyzed. Statistical
      analyses were performed using F test. Results: Immediate success of RFCA was
      achieved in 104 cases (96.3%, 104/108) and 4 cases (3.7%, 4/108) failed. The PVCs
      recurred during follow-up of over 6 months in 5 cases (4.8%, 5/104) . There were
      no severe complications related to the procedure. The sites of PVCs origin, in 52
      cases originated from right ventricular outflow track (48.2%, 52/108) , 17 cases
      originated from left ventricular outflow track (15.7%, 17/108) and 26 cases
      originated from tricuspid annulus (24.1%, 26/108) . Among the three predilection
      sites of PVCs, the operation time was (141+/-46) min for right ventricular
      outflow track, (155+/-50) min for left ventricular outflow track, and (166+/-57)
      min for tricuspid annulus. However, the difference was not statistically
      significant (F=1.79, P=0.17) . X-ray exposure time was (14+/-8) minutes for right
      ventricular outflow track ablation, (32+/-14) minutes for left ventricular
      outflow track ablation and (16+/-8) minutes for tricuspid annulus ablation
      respectively. The exposure time for the ablation on left ventricle was
      significantly longer than the other two sites (F=5.12, P=0.018) . Conclusion:
      RFCA is safe and effective for PVCs in children with high success rate and low
      recurrence and complication rates.

PMID- 29342993
TI  - [Analysis of prognosis and associated risk factors in pediatric idiopathic
      pulmonary arterial hypertension].
AB  - Objective: To analyze the prognosis and associated risk factors of pediatric
      idiopathic pulmonary arterial hypertension. Methods: A total of 119 patients
      under 18 years of age diagnosed as idiopathic pulmonary arterial hypertension in
      the Pulmonary Arterial Hypertension Center in Beijing Anzhen Hospital between
      June 2007 and May 2017 were enrolled in this retrospective study. The clinical
      informations and follow-up data were collected. The endpoints of follow-up were
      defined as death or undergoing lung transplantation. Kaplan-Meier survival curve
      was used to assess the survival,and the COX risk regression model was used to
      analyze the prognostic risk factors. Results: The mean age at diagnosis was
      (5.9+/-4.2) years. For 92 (77.5%) patients, the main reason for visit was
      decreased activity with shortness of breath after exercise. Seventy patients
      (58.8%) were in baseline NYHA functional class III-IV and 49 patients (41.2%)
      were in NYHA functional class I-II. The mean systolic pulmonary arterial pressure
      estimated by echocardiography was (90+/-23) mmHg (1 mmHg=0.133 kPa) . Right heart
      catheterization was performed in 50 patients. Hemodynamic parameters revealed
      that the mean pulmonary artery pressure was (66+/-19) mmHg. Mean right atrium
      pressure was (8.5+/-3.4) mmHg. Mean pulmonary vascular resistance index was (17+/
      9) wood.m(2) and the mean cardiac index was (3.4+/-1.3)L/m(2); 100 patients
      (84.0%) received targeted therapy in which 55 patients (46.2%) were on
      monotherapy,40 patients (33.6%) were on dual therapy and 5 patients (4.2%) were
      on triple therapy. The mean time of follow-up was 22.0 months (0-108 months).
      During follow-up, 43 patients (36.1%) died and 1 patient received double-lung
      transplantation. Main causes of death including right heart failure, pulmonary
      hypertension crisis, asphyxia and massive hemoptysis. The mean survival time from
      diagnosis was 37.0 months,1-,2-,3-and 5-year survival rates were 86.3%, 72.2%,
      51.4%and 37.8% respectively. Survival analysis showed that patients in baseline
      NYHA functional class I-II had better prognosis. COX regression analysis showed
      that NYHA function class, edema, increased total bilirubin and troponin
      concentration and the pulmonary artery and aorta diameter ratio measured by
      echocardiogram are risk factors of pediatric IPAH (HR=2.310, 2.723, 1.066, 1.696,
      3.719, P=0.028, 0.005, 0.001, 0.024, 0.030) . While the existence of aterial
      septal defect or patent foramen ovale, using bosentan and phosphodiesterase
      inhibitors(,) dual or triple therapy were protective factors (HR=0.563, 0.559,
      0.603, 0.682, 0.044, P=0.169, 0.076, 0.115, 0.258, 0.220) . In multivariate
      analysis only edema associated with decreased survival (HR=2.398, P=0.025) .
      Conclusion: Childhood idiopathic pulmonary arterial hypertension patients are
      seriously ill at visit. Worse cardiac function classification at visit associate
      with high mortality. Target therapy including using bosentan, dual or triple
      therapy can improve survival.

PMID- 29342994
TI  - [Report of antimicrobial resistance surveillance program in Chinese children in
      2016].
AB  - Objective: To analyze the antimicrobial resistance profile in Chinese children.
      Methods: This was a prevalence survey. From January 1 through December 31, 2016,
      the isolates were collected from 10 tertiary children hospitals in China.
      Antimicrobial susceptibility testing was carried out by routine laboratory
      methods. The penicillin susceptibility of streptococcus pneumonia and Meropenem
      susceptibility of gram-negative bacteria were detected by E-test and disk
      diffusion method respectively. Antimicrobial susceptibility results were
      interpreted according to the criteria of Clinical and Laboratory Standards
      Institute (CLSI) Guideline 2016. The data of antimicrobial susceptibility testing
      of isolates from either the different patients (neonatal group and non-neonatal
      group) or various sources were analyzed by WHONET 5.6 software. Results: A total
      of 56 241 isolates were collected, of which 41.5% (23 328 isolates) were gram
      positive organisms and 58.5% (32 886 isolates) gram-negative organisms. The five
      leading pathogens were Escherichia coli (7 995/56 214, 14.2%), Straphylococcus
      aureus (6 468/56 214, 11.5%), Streptococcus pneumonia (6 225/56 214, 11.1%),
      Haemophilus influenza (5 435/56 214, 9.7%) and Klebsiella pneumonia (4 523/56
      214, 8.0%). The Meropenem resistance rates of Klebsiella pneumonia, Enterobacter
      cloacae, Escherichia coil, Pseudomonas aeruginosa, Acinetobacter baumonia
      isolates were 27.4% (326/1 189) , 8.1% (29/358) , 2.0% (27/1 362) , 19.5%
      (34/174) , 49.7% (230/463) in neonatal group and 15.4% (512/3 327) , 4.8%
      (40/841) , 2.3% (151/6 564) , 13.7% (252/1 840) , and 53.4% (860/1 611) in non
      neonatal group. The Methicillin-resistant Staphylococcus aureus (MRSA) rates of
      neonatal group and non-neonatal group were 46.2% (649/1 404) and 33.3% (1 668/5
      010) . The penicillin non-susceptible rates of Streptococcus pneumonia in the two
      groups were 17.6% (6/34) and 18.2% (1 121/6 158) respectively. The beta-lactamase
      positive rates of Haemophilus pneumonia isolates in the neonatal group and non
      neonatal groups were 33.8% (47/139) and 44.4% (2 345/5 282) respectively.
      Conclusion: This investigation highlights the worrisome trend of antimicrobial
      resistance in children, especially among neonatal patients in China.

PMID- 29342995
TI  - [Pediatric myeloid neoplasms associated with eosinophilia and platelet-derived
      growth factor receptor beta gene rearrangement: a case report and literature
      review].
AB  - Objective: To investigate the clinical features and therapeutic strategies of
      childhood myeloid neoplasms associated with eosinophilia and platelet-derived
      growth factor receptor beta (PDGFRB) gene rearrangement. Methods: Clinical data
      of myeloid neoplasms associated with eosinophilia and t (1;5) (q21;q33)
      chromosomal translocation of PDGFRB gene rearrangement in a child hospitalized in
      Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical
      Sciences on May 2015 was collected and analyzed. Using'eosinophilia
      child'and'PDGFRB'as keywords, the relevant reports in literature were searched
      from China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge
      Service Platform, and Biomedical Literature Database (PubMed) until April 2017.
      Results: The patient was a boy, 19 months old, who began to get sick at six
      months after birth, with the main clinical manifestations of high fever,
      diarrhea, epistaxis and hepatosplenomegaly. Peripheral blood smear showed a
      significant elevation in white blood cells (127*10(9)/L) and
      eosinophils(20.32*10(9)/L). Bone marrow examination showed hyperplastic marrow,
      increased proportion of granulocytes, apparent visible eosinophils and decreased
      megakaryocytes. Chromosome karyotype detection revealed t (1; 5) (q21; q33)
      translocation. Fluorescence in situ hybridization (FISH) examination uncovered
      that PDGFRB gene rearrangement was positive. The final diagnosis was myeloid
      neoplasms with eosinophilia and PDGFRB gene rearrangement. After treatment with
      oral imatinib 100 mg, once a day for 2 months, complete hematologic remission,
      complete cytogenetic and molecular remission were all achieved. The relevant
      literature was reviewed, no Chinese cases had been reported, 6 reports in English
      literature have complete clinical data. Four cases had t (1; 5) translocation.
      Four pediatric patients treated with imatinib achieved complete remission.
      Conclusion: Myeloid neoplasms associated with eosinophilia and PDGFRB gene
      rearrangement is extremely rare in children. Imatinib treatment can make these
      patients quickly achieve complete hematologic remission, complete cytogenetic and
      molecular remission. Imatinib should be recommended as the first line treatment
      of these patients.

PMID- 29342996
TI  - [Optimal energy supply in different age groups of critically ill children on
      mechanical ventilation].
AB  - Objective: To analyze the resting energy expenditure and optimal energy supply in
      different age groups of critically ill children on mechanical ventilation in
      pediatric intensive care unit (PICU). Methods: Patients on mechanical ventilation
      hospitalized in PICU of Beijing Children's Hospital from March 2015 to March 2016
      were enrolled prospectively. Resting energy expenditure of patients was
      calculated by US Med Graphic company critical care management (CCM) energy
      metabolism test system after mechanical ventilation. Patients were divided into
      three groups:<3 years, 3-10 years, and >10 years. The relationship between the
      measured and predictive resting energy expenditure was analyzed with correlation
      analysis; while the metabolism status and the optimal energy supply in different
      age groups were analyzed with chi square test and variance analysis. Results: A
      total of 102 patients were enrolled, the measured resting energy expenditure all
      correlated with predictive resting energy expenditure in different age groups (<3
      years (r=0.3, P=0.0) ; 3~10 years (r=0.6, P=0.0) ;>10 years (r=0.5, P=0.0) ) . A
      total of 40 cases in < 3 years group, including: 14 cases of low metabolism
      (35%), 14 cases of normal metabolism (35%), and 12 cases of high metabolism
      (30%); 45 cases in 3-10 years group, including: 22 cases of low metabolism (49%),
      19 cases of normal metabolism (42%), 4 cases of high metabolism (9%); 17 cases
      in>10 years group, including: 12 cases of low metabolism (71%), 4 cases of normal
      metabolism (23%), 1 case of high metabolism (6%). Metabolism status showed
      significant differences between different age groups (chi(2)=11.30, P<0.01, r=
      0.01). Infants had higher metabolic status, which lessened with aging. The total
      average actual energy requirement was (210+/-84) kJ/ (kg?d) . There were
      significant differences in actual energy requirement between age groups (F=46.57,
      P<0.001), with (277+/-77) kJ/ (kg?d) in<3 years group, (184+/-53) kJ/ (kg?d) in 3
      10 years group, and (120+/-30) kJ/ (kg?d) in>10 years group. Conclusion: The
      resting energy metabolism of the critically ill children on mechanical
      ventilation is negatively related to the age. The actual energy requirement
      should be calculated according to different ages.

PMID- 29342997
TI  - [X-linked inhibitor of apoptosis deficiency manifested as Crohn's disease: a case
      report and literature review].
AB  - Objective: To analyze the clinical characteristics of X-linked inhibitor of
      apoptosis (XIAP) deficient patients with clinical manifestation of Crohn's
      disease. Methods: Clinical manifestations, laboratory investigations, genetic
      testing and therapeutic interventions of one case of XIAP deficiency who was
      admitted to Department of Gastroenterology in Children's Hospital, Zhejiang
      University School of Medicine in May 2016 were summarized. PubMed and Chinese
      database for articles published from January 2016 to June 2017 were searched
      using the key words of'Crohn's disease'and'XIAP', and the relevant literature was
      reviewed. Results: The case we reported was a 6-year-1-month-old boy with
      recurrent bloody stool for 2 months, and abdominal pain with fever for 2 weeks.
      The patient had a past history of hemophagocytic lymphohistiocytosis (HLH) and
      epilepsy in the past one year. Complete blood cell count showed mild anemia
      (Hb108 g/L). The patient had an elevated high-sensitivity C reactive protein (86
      mg/L) and erythrocyte sedimentation rate (46 mm/1h) . White blood cells, pus
      cells and red blood cells were found on routine stool examination. Biochemical
      panel showed hypoalbuminemia (25.2 g/L) , elevated transaminase (alanine
      aminotransferase 175 U/L, aspartate transaminase 229 U/L) , hypertriglyceridemia
      (4.41 mmol/L) , and hyperferritinemia (>1 650.0 MUg/L) . Magnetic resonance
      enterography revealed the intestinal wall thickening and increased enhancement in
      parts of illeum and colon. Capsule endoscopy revealed multiple ulcers in jejunum.
      Colonoscopy showed multiple ulcers in colon and the pathological examination
      revealed chronic inflammation in mucosa of terminal ileum and colon, which was
      combined with partial necrosis and ulceration. Some phagocytes were seen in bone
      marrow smears. The patient was given multiple diagnoses, including hemophagocytic
      lymphohistiocytosis, Crohn's disease, sepsis, epilepsy, severe malnutrition, and
      hypoproteinemia. The pediatric Crohn's disease activity index (PCDAI) was 37.5.
      Genetic testing identified a hemizygotic mutation of c.910G>T chrX:123022501
      p.G304X in XIAP. The parents had no such mutation. The patient showed response to
      infliximab with oral intake of mercaptopurine and corticosteroids, and had
      remission with PCDAI of 0. There were 9 relevant articles (Chinese 0 English 9),
      which showed 33.3% XIAP deficient patients manifested with inflammatory bowel
      disease(IBD), who might have other manifestations such as hemophagocytic
      lymphohistiocytosis or splenomegaly simultaneously or sequentially. Those
      patients showed poor response to monotherapy. Conclusion: XIAP deficient patients
      have various clinical manifestations. Genetic testing is important to those male
      pediatric IBD patients who have the complicated symptoms or little response to
      standard therapy.

PMID- 29342998
TI  - [X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection,
      and neoplasia: report of a family and literature review].
AB  - Objective: To investigate the clinical features and genetic characteristics of
      cases with X-linked immunodeficiency with magnesium defect, Epstein-Barr virus
      (EBV) infection, and neoplasia (XMEN). Methods: Characteristics of clinical
      material, immunological data and gene mutation of two cases with XMEN in the same
      family in China were retrospectively analyzed. The related reports literature
      were searched by using search terms'MAGT1 gene'or'XMEN'. Results: The proband, a
      2-year-eight-month old boy, was admitted due to 'Urine with deepened color for
      two days and yellow stained skin for one day'. He had suffered from recurrent
      upper respiratory tract infection and sinusitis previously. Hemoglobin level was
      38 g/L. The absolute count of reticulocytes was 223.2*10(9)/L. Urobilinogen level
      was 38 MUmol/L (3-16 MUmol/L). Coomb's test was positive. Both total (77.2
      MUmol/L) and indirect bilirubin (66 MUmol/L) levels were elevated. There was an
      inverted CD4(+)/CD8(+)T cell ratio (0.89). The gene sequencing results showed
      MAGT1 gene c.472delG, p.D158Mfs*6 mutation. His 1-year-6-month old brother, was
      also identified to have MAGT1 gene c.472delG, p.D158Mfs*6 mutation.The younger
      brother mainly suffered from recurrent upper respiratory tract infection,
      accompanied by an inverted CD4(+)/CD8(+)T cell ratio (0.45), an elevated ratio
      and number of total B cells (45.7%). A total of 7 reports were retrieved
      including 11 male cases caused by MAGT1 gene mutation. These 11 cases were
      characterized by EBV viremia (11 cases), recurrent upper respiratory tract
      infection, otitis media or sinusitis (10 cases), secondary neoplasia diseases (8
      cases), reduction of CD4(+)/CD8(+) T cell ratio (7 cases),and autoimmune
      thrombocytopenia or hemolytic anemia (2 cases). Conclusion: XMEN often manifests
      as male onset, recurrent upper respiratory tract infection, otitis media or
      sinusitis, EBV viremia, lymphoproliferative disease or lymphoma, autoimmune
      diseases and reduction of CD4(+)/CD8 (+)T cell ratio. NKG2D expression in NK
      cells is significantly reduced, and gene sequencing analysis shows a pathogenic
      mutation in MAGT1 gene.

PMID- 29343000
TI  - [X-linked hyper-IgM syndrome complicated interstitial lung disease induced by
      virus in two pediatric cases].

PMID- 29343001
TI  - [Pulmonary mucoepidermoid carcinoma in a child].

PMID- 29342999
TI  - [Risk factors analysis and prognosis of renal pelvis dilatation in high-risk
      infants in monocenter].
AB  - Objective: To explore the prognosis and risk factors of pyelectasis in high-risk
      infants. Methods: This was a retrospective study. Totally 960 high-risk infants,
      who accepted type B ultrasonic examination for fetus at 28th week of gestation
      and for newborns in 48 hours after birth, were included in the study in
      departments of obstetrics and eonatology, Shunyi Maternal and Children's Hospital
      of Beijing Children's Hospital during May 2012 to April 2013. The degree of
      pyelectasis was classified using Grignon grade and the paients were followed up
      for 3 years. The factors of epidemiology, high risk pregnant women, fetus and
      high-risk newborns that relate to pyelectasis were summarized. High-risk factors
      were analyzed by using logistic multivariate regression analysis. Results: Of 960
      high-risk infants, 103 had abnormal urinary ultrasound results, 87 (9.1% of high
      risk infants) were diagnosed with pyelectasis, 16 (1.7% of high-risk infants)
      were diagnosed with congenital anomalies of the kidney and urinary tract.
      According to the degree of pyelectasis, 68 infants were Grignon grade I,
      male:female ratio=5.8?1, left side:right side ratio=1.91?1; 19 infants were
      Grignon grade II, male:female ratio=5.33?1, left side:right side ratio=2.12?1.
      Postnatal follow-up results showed that pyelectasis disappeared in 48 cases (55%
      of pyelectasis cae), 40 infants were Grignon grade I (59% of all Grignon grade I
      patients), 8 infants were Grignon grade II (42% of all Grignon grade II
      patients); The result of risk factors analysis showed that the risk of
      pyelectasis in males was 4.368 times that of females (95%CI: 2.33-8.189, P<0.05);
      the risk of pyelectasis in low birth weight infants was 22.434 times that of non
      low birth weight infants (95% CI: 5.883-85.547, P<0.05). Conclusion: The
      incidence of pyelectasis in high-risk infants was 9.1%. The mitigation rate of
      pyelectasis in Grignon grade I to II in fetal or newborn period is high. Patients
      in Grignon grade III and above in fetal or new born period had high risk of
      congenital anomalies of the kidney and urinary tract. The risk of pyelectasis of
      male was higher than that of female; the risk of pyelectasis of low birth weight
      infant was higher than appropriate for gestational age infants.

PMID- 29343002
TI  - [A case of abdominal Castleman disease].

PMID- 29343003
TI  - [Schuurs-Hoeijmakers syndrome in a child].

PMID- 29343004
TI  - [Fanconi-Bickel syndrome with SLC2A2 gene mutation in a child].

PMID- 29343005
TI  - [Role of long noncoding RNA in chronic hepatitis B infection].

PMID- 29343006
TI  - [Epidemiology of heart arrest in children].

PMID- 29343008
TI  - [Effects of obstructive sleep apnea syndrome on vascular endothelial function in
      and mechanisms children].

PMID- 29343007
TI  - [Introduction to the 6th National Conference of Pediatric Syncope].

PMID- 29343009
TI  - [The thinking and challenge from the drug-resistant tuberculosis guidelines by
      World Health Organization].

PMID- 29343010
TI  - [Diagnosis and treatment of extrapulmonary non-tuberculous mycobacterial
      diseases].

PMID- 29343011
TI  - [Molecular genetic mechanism of anti-tuberculous drug induced liver injury].

PMID- 29343012
TI  - [The effectiveness of individualized treatment regimen on smear-positive
      retreatment pulmonary tuberculosis with mono- and poly-drug resistance].
AB  - Objective: To analyze and evaluate the effectiveness of individualized treatment
      regimen in the therapy of smear-positive retreatment pulmonary tuberculosis with
      mono-and poly-drug resistance, and therefor to provide information on how to
      develop rational individualized regimen for retreatment tuberculosis cases with
      drug resistance. Methods: This was a multi-centered, prospective cohort study.
      Totally 254 cases of sputum positive tuberculosis with previous treatment history
      during the period from July 1, 2009 to August 30, 2016 were included in the
      analysis. All the cases were randomly divided into 3 groups and received therapy
      after randomization into treatment groups. After 3 months, cases with multidrug
      resistant tuberculosis, extensively drug-resistant tuberculosis, non-tuberculosis
      mycobacterial infection and those with smear-positive but culture-negative
      tuberculosis were excluded according to result of sputum culture and drug
      susceptibility test (DST). In treatment group A (individualized treatment group),
      86 cases with an average age of (42.1+/-13.7) years for men and (38.5+/-12.8)
      years for women, were treated with individualized regimen, which allowed drug
      replacement on the basis of standard regimen (2SHRZE/6HRE) according to DST
      result. Treatment duration was recalculated after drug replacement and the total
      length should be 12 months or more. If the DST result did not show drug
      resistance, the patients would continue the 8 months' standard treatment. In
      treatment group B (intensified retreatment regimen group), 86 cases with an
      average age of (43.2+/-14.2) years for man and (37.9+/-14.1) years for women,
      received intensified retreatment regimen (2HL(2)EZS/2HL(2)EZS(3)/4HL(2)E). The
      dose for H was 0.3 g/d for patients with body weight <50 kg, and 0.4~0.5 g/d for
      higher body weight (>=50 kg); The doses for L(2,)E and Z were 0.6 g, 2/w; 0.75,
      1/d and 0.5g, 3/d. In treatment group C (standard treatment group), 82 cases with
      an average of (42.5+/-11.9) years for man and (38.6+/-12.8) years for women, were
      treated with standardized regimen recommended by national tuberculosis program
      (2HREZS/6HRE). In both group B and C, the total treatment duration was 8 months
      and the drugs were not replaced for mono-and poly-drug resistance. Treatment
      outcomes of the 3 groups were analyzed, the status of drug replacement in group A
      was analyzed, and the adjustment of dose of H and R according to patients' body
      weight was observed. SPSS 19.0 was used for data analysis. Results: The treatment
      cure rates for group A, B and C were 73.3%(63/86), 76.7%(66/86) and 50%(41/82),
      and the treatment success rates were 80.2%(69/86), 84.9%(73/86) and 62.2%(51/82)
      respectively. Treatment failure was 8.1%(7/86), 4.7%(4/86) and 19.5%(16/82) in 3
      groups. There were significant differences in the above indicators for group A
      and B in comparison with group C(chi(2)=13.127, P=0.001). However, there was no
      difference observed between group A and B(chi(2)=0.646, P=0.422). In group A,
      tuberculosis specialized hospitals using regular doses for R was only
      38.7%(12/31). After 3 years' follow-up, no-relapse-success for group A was 66.7%
      (10/15). Conclusions: Inappropriate individualized treatment would increase
      treatment failure for retreatment tuberculosis. Higher doses of H and R and
      prolonged extensive therapy phase could contribute to increased treatment
      success.

PMID- 29343013
TI  - [The plasma level and gene expression in peripheral blood of interleukin-35 in
      patients with sarcoidosis and its clinical significance].
AB  - Objective: To investigate the expression of interleukin(IL)-35 protein and gene
      in peripheral blood of patients with sarcoidosis and its clinical significance.
      Methods: Peripheral blood samples from 98 patients with sarcoidosis and 98
      healthy volunteers were collected at Peking Union Medical College Hospital
      between January 2016 and March 2017. The plasma levels of IL-35 were detected by
      enzyme-linked immunosorbent assays (ELISA), and the relationship between IL-35
      and the clinical characteristics was analyzed. Real-time quantitative PCR was
      used to detect the expression levels of IL-35 subunit EBI3, p35 and T regulatory
      cell transcription factor Foxp3 mRNA in peripheral blood mononuclear cells, and
      their correlations were analyzed. Results: The plasma levels of IL-35 in patients
      with sarcoidosis (44+/-12) ng/L was significantly lower than that in the normal
      control group (55+/-12) ng/L (P<0.001). There was a positive correlation between
      the plasma levels of IL-35 and D(L)CO% predicted values (r=0.76, P<0.001), but it
      showed no significantly correlation with other clinical parameters. The
      expression of EBI3 and Foxp3 mRNA in peripheral blood mononuclear cells of
      patients with sarcoidosis (1.54+/-0.74, 0.92+/-0.36) were significantly lower
      than those in the normal control group respectively (2.12+/-0.61, 1.10+/-0.27,
      all P<0.05). There was a significant positive correlation between the expression
      of EBI3 and Foxp3 mRNA in the sarcoidosis group (r=0.786, P<0.001). Conclusion:
      IL-35 may be involved in the inflammatory process of sarcoidosis and play an
      important role in the pathogenesis of the disease.

PMID- 29343014
TI  - [Correlation between peripheral venous oxygen saturation and hemodynamic
      parameters in patients with pulmonary hypertension].
AB  - Objective: To investigate the correlation of peripheral venous oxygen saturation
      (SpvO(2)) with mixed venous oxygen saturation (SvO(2)), pulmonary vascular
      resistance (PVR) and cardiac index (CI) in patients with pulmonary hypertension
      (PH), in order to predict these parameters using SpvO(2) and assess the prognosis
      of patients. Methods: Hospitalized patients diagnosed with PH by right heart
      catheterization in the Guangzhou Institute of Respiratory Diseases from July 2015
      to October 2016 were retrospectively analyzed. Parameters during the right heart
      catheterization, including SvO(2,)SpvO(2,)cardiac output (CO) and mean pulmonary
      arterial pressure (mPAP) were recorded, while CI, PVR and other parameters were
      indirectly calculated. The correlation between SpvO(2) and SvO(2,)CO, CI, mPAP,
      PVR and other parameters were respectively analyzed and compared between groups.
      Results: A total of 77 PH patients were selected, which comprised of 39 males and
      38 females. The results revealed that SpvO(2) was correlated positively with
      SvO(2,)CI and PaO(2) (P<0.05), but negatively with PVR, total pulmonary
      resistance (TPR), systemic vascular resistance, right atrial diameter and right
      ventricular diameter (P<0.05). In the group with SpvO(2) <65%, the dilation of
      the right atrium and right ventricle was more significant, the WHO heart function
      grade was worse, CI, systemic systolic pressure and mean systemic pressure were
      lower, and PVR and TPR were higher, as compared to those in the group with
      SpvO(2) >=65%. (P<0.05). Conclusions: There was good consistency between SpvO(2)
      and SvO(2). Furthermore, SpvO(2) could indirectly reflect the CI, PVR and changes
      in right heart structure of PH patients, providing reference for the clinical
      prediction of CI and PVR, as well as the prognosis of PH patients, through the
      use of SpvO(2). Low SpvO(2) indicated a severe condition and poor prognosis.

PMID- 29343015
TI  - [Clinical and imaging features of pulmonary veno-occlusive disease and pulmonary
      capillary hemangioma].
AB  - Objective: To improve the diagnosis and treatment of the pulmonary veno-occlusive
      disease (PVOD) and pulmonary capillary hemangioma (PCH). Methods: The clinical
      features, radiological findings, laboratory testing and treatment in 8 cases of
      PVOD/PCH which was diagnosed from 2013 to 2017 were described. Results: PVOD/PCH
      was rare. The clinical symptoms were easily confused with IPAH, but the decrease
      of hypoxemia, clubbing, D(L)CO were more obvious, and the imaging features of
      HRCT were helpful for PVOD/PCH diagnosis. Combined with gene testing, it was
      helpful to diagnose PVOD/PCH and avoid the risk of surgical biopsy. Conclusion:
      PVOD and PCH are rare type of pulmonary vascular diseases. According to clinical
      manifestations, physical examination, pulmonary function test results, HRCT
      imaging, CPET and gene detection results, PVOD or PCH can be diagnosed.

PMID- 29343017
TI  - [Review of meropenem-clavulanate combination in the treatment of multidrug
      resistant and extensively durg-resistant tuberculosis].

PMID- 29343016
TI  - [Effectiveness and safety in bronchoscopy under anesthesia with fentanyl combined
      with midazolam].
AB  - Objective: To study the effectiveness and safety in bronchoscopy under anesthesia
      with fentanyl combined with midazolam. Methods: We randomly allocated 132
      patients( male 69, female 63, median age 62.9 years)requiring bronchoscopy in
      Beijing Xuanwu Hospital into 2 groups during January 2015 to December 2016.The
      trial group included 66 patients, receiving fentanyl combined with midazolam for
      anesthesia, while the control group of 66 patients receiving 2% lidocaine for
      topical anesthesia.In the trial group, there were 37 males and 29 females, with a
      median age of 63 years (range 26-82). In the control group, there were 36 males
      and 30 females, with a median age of 62.8 years (range 30-82). The pulse, mean
      arterial pressure, and the oxygen saturation of the patients were recorded before
      anesthesia and 5 minutes after deep anesthesia was reached. Changes of vital
      signs and adverse reactions during the bronchoscopy were also observed. Results:
      The fluctuation of pulse(12.3+/-2.3)/min, mean arterial pressure(5.9+/-2.2)mmHg(1
      mmHg=0.133 kPa) and oxygen saturation(4.4+/-1.3)%was lower in the trial group as
      compared to that of the control group, pulse(21.9+/-1.8)/min, mean arterial
      pressure(7.1+/-2.3)mmHg, oxygen saturation(13.3+/-4.2)%, P<0.001.Five minutes
      after anesthesia, the pulse(80.0+/-11.9)/min, the mean arterial pressure(95.0+/
      9.7)mmHg and the oxygen saturation(90.0+/-5.67)%of patients in the trial group
      were lower than those in the control group [pulse(90.3+/-17.0)/min, mean arterial
      pressure(102.7+/-12.4)mmHg, oxygen saturation(96.5+/-3.0)%], the differences
      being statistically significant(P<0.001). The trial group also showed smaller
      fluctuation, better tolerance, and fewer adverse reaction sthan the control
      group. Conclusion: Fentanyl combined with midazolam is safe and effective in
      bronchoscopy with fewer adverse reactions, but its early effect on the vital
      signs should be monitored and stricter indications may be needed.

PMID- 29343018
TI  - [Research progress of exosomes in lung diseases].

PMID- 29343019
TI  - [Advances in preoperative screening of obstructive sleep apnea hypopnea
      syndrome].

PMID- 29343020
TI  - [The application of noninvasive positive pressure ventilation to a pulmonary
      rehabilitation program in patients with chronic obstructive pulmonary Disease].

PMID- 29343021
TI  - [The role of aquaporin in the development of pulmonary diseases].

PMID- 29343022
TI  - [Inheriting the excellence to innovate medical research in China].

PMID- 29343023
TI  - [Emphasis on perioperative and long-term treatment is the key to improve the
      prognosis of patients with craniopharyngiom].

PMID- 29343024
TI  - [Hypopituitarism mode in patients with craniopharyngioma in relation to tumor
      growth pattern].
AB  - Objective: To investigate the pituitary hormone changes of patients with
      craniopharyngioma of different growth patterns during perioperative period and
      follow up time. Methods: Retrospective studies were performed on 212 cases of
      primary craniopharyngioma patient who received total tumor excision surgery in
      our hospital from January 2001 to May 2012. The characteristics of pituitary
      hormone and associated clinical manifestation during preoperative, perioperative
      and postoperative periods were analyzed according to the QST surgical
      classification. Results: One hundred and seventy-seven (83.5%) of patients
      present preoperative hypopituitarism, 36 of them were panhypopituitarism. The
      hypopituitarism condition was exacerbated during the early stage of post
      operation period. The abnormal rates of HPA and HPT during the follow up were
      60.1% and 58.3% respectively and hormone replacement treatment was needed for
      these patients. Craniopharyngioma of different growth patterns showed diversities
      in the characteristics of hypopituitarism. Conclusion: QST surgical
      classification was closely associated with the pattern of hypopituitarism, it can
      help to optimize treatment and prognosis estimation, and could be important
      criterion for improving the clinical practice of neuroendocrine monitoring,
      treatment and health education of patients with craniopharyngioma.

PMID- 29343025
TI  - [Correlation between the parameters of acoustic cardiography and BNP, LVEF and
      cardiac function grading in patients with chronic heart failure].
AB  - Objective: To explore the correlation between the parameters of the new
      generation of Acoustic Cardiography and brain natriuretic peptide (BNP), left
      ventricular ejection fraction (LVEF) and cardiac function grading in the
      diagnosis of heart failure. Methods: One hundred and sixty-eight inpatients, who
      were hospitalized in Department of Cardiology, Haikou People's Hospital from May
      2016 to July 2017, were enrolled as heart failure group, including NYHA class
      I(n=29), NYHA class II(n=40), NYHA class III(n=64), NYHA class IV (n=35). And
      eighty-seven patients with normal cardiac function were selected as healthy
      control group. The data of the two groups were analyzed after the Acoustic
      Cardiography test, BNP determination and LVEF examination. Results: The
      differences in QRS duration, electromechanical activation time (EMAT), EMAT%,
      systolic dysfunction index (SDI), third heart sound (S3) and other indicators
      among the groups with different levels of cardiac function were statistically
      significant (P<0.05). The difference in left ventricular systolic time (LVST)
      between the cardiac function grade I and healthy group was not significant
      (P>0.05), while the differences among the rest groups were significant. There was
      a positive correlation between QRS duration, EMAT%, SDI, S3 and BNP (t=9.46,
      11.38, 12.14, 9.67, respectively, P<0.05); LVST and BNP were negatively
      correlated (t=-14.27, P<0.05). There was a negative correlation between QRS
      duration, EMAT%, SDI, S3 and LVEF (t=11.24, -8.764, -2.393, -0.579, respectively,
      P<0.05). There was a positive correlation between LVST and LVEF (t=23.48,
      P<0.05). There was a positive correlation between QRS duration, EMAT%, SDI, S3
      and cardiac function grading (beta=0.003, 0.234, 0.419, 0.352, respectively,
      P<0.05). There was a negative correlation between LVST and cardiac function grade
      (beta=-0.021, P<0.05). Conclusion: The parameters of the Acoustic Cardiography
      test (EMAT%, EMAT, SDI, S3 ) are closely related to BNP, LVEF and cardiac
      function grading, and can be used as assistant indexes for the diagnosis and
      evaluation of heart failure.

PMID- 29343026
TI  - [Applied research of "quadri-low" combined with automatic tube current modulation
      and iterative model reconstruction technology in head and neck CT angiography].
AB  - Objective: To investigate the feasibility of low tube voltage, low contrast
      medium concentration, injection rate and volume (quadri-low) combined with
      automatic tube current modulation (ATCM) and iterative model reconstruction (IMR)
      technology in head and neck CT angiography (CTA). Methods: A total of 70 patients
      whose body mass index (BMI)<25 kg/m(2) underwent head and neck CTA and digital
      subtraction angiography (DSA) from January to July 2017 were enrolled in this
      prospective study. According to random number table, patients were divided into
      two groups: group A (n=35) was scanned according to the protocol of 120 kV, 150
      mAs, 50 ml and 5 ml/s iopromide (370 mg/ml) and filtered back projection (FBP)
      reconstruction; group B (n=35) was scanned with 80 kV, ATCM with mean tube
      current of 100 mAs, 30 ml and 3 ml/s iohexol (300 mg/ml) and IMR; the other
      parameters kept consistent between the two groups. The maximum transverse neck
      diameter at the level of the hyoid bone, artery CT value and image noise were
      measured, signal to noise ratio (SNR), contrast to noise ratio (CNR) and figure
      of merit (FOM) were calculated, and the image quality was evaluated subjectively
      and compared with those reconstructed by DSA. Scan length, volume CT dose index
      (CTDIvol) and dose length product (DLP) were recorded, and the effective dose
      (ED) was calculated. The chi-square and independent-sample t tests were used to
      compare the inter-group differences in these aforementioned data. Resutls: No
      significant difference was found in general information between the two groups.
      No significant difference existed in artery CT value, image noise, SNR and CNR
      between the two groups (t=-1.170-1.365, all P>0.05); however, the FOM of group B
      (74+/-40) was significantly higher than that in group A (12+/-4) (Z=-7.195,
      P=0.000). The image quality of the two groups met the requirement of clinical
      diagnosis[(4.1+/-0.7) vs (4.2+/-0.8) points, Z=-0.592, P>0.05], no significant
      difference was found in subjective evaluation and diagnostic efficacy. The
      CTDIvol, DLP and ED in group B were all significantly lower than those in group A
      (Z=-7.728, -7.202, -7.206, all P<0.05). The iodine load and iodine delivery rate
      (IDR) of group B was lower than that of group A (18.5 g vs 9.0 g, 1.85 mg/s vs
      0.90 mg/s), and they were reduced for 51.4% in group B. Conclusions: For patients
      of BMI <25 kg/m(2,) low tube voltage, low contrast medium concentration,
      injection rate and volume combined with ATCM and IMR technology can significantly
      decrease radiation dose, iodine load and IDR while maintain the image quality in
      head and neck CTA examination.

PMID- 29343027
TI  - [Using creatinine reduction ratio as a predictor for delayed graft function of
      kindey transplant recipients from donor of cardiac death].
AB  - Objective: To explore the relationship between creatinine reduction ratio (CRR)
      and delayed graft function among kidney transplant recipients from donor of
      cardiac death (DCD). To define the value of CRR to predict delayed graft function
      (DGF) in early post-transplant period. Method: 86 patients were included, who
      received renal transplantation from DCD during Jan 1(st) 2011 to Jun 30(th) 2016.
      We performed a retrospective study and collected creatinine data within 3 days
      post-operation and marked them with Cr1, Cr2 , Cr3, and then calculated
      creatinine reduction ratio day-2 (CRR 2) =(Cr1-Cr2)/Cr1*100% and creatinine
      reduction ratio day-3 (CRR 3)=[(Cr1-Cr2)/Cr1+ (Cr2-Cr3)/Cr2]/2*100%. Patients
      were divided into two groups by DGF or not. We compared the CRR differenc between
      DGF group and no DGF group, and drew the receiver operating characteristic curve
      (ROC curve) to find out the cut-off value to predict delayed graft function.
      Results: Among 86 patients, DGF appeared in 17 patients. The incidence of DGF was
      19.8%. The CRR 2 of patients in no DGF group was (37.5+/-17.4)% while patients in
      DGF group was (2.0+/-24.8)% (P<0.001). The CRR 3 of patients in no DGF group was
      (32.5+/-13.1)%, while patients in DGF group was (6.8+/-17.1)% (P<0.001).
      Acorrding to ROC curve, when cut-off value of CRR 2 was defined as <20.7%, the
      predicted value of DGF was the best, sensitivity was 85.5%, specificity was
      76.5%, and area under the curve was 0.876. In the same way, when CRR 3 was
      defined as <17.6%, sensitivity was 89.9%, specificity was 76.5%, area under the
      curve was 0.872. Conclusion: It is reliable to predict DGF by CRR during early
      post-operative period. CRR shows high sensitivity and specificity and it is
      simple. It could guide the adjustion of immunosuppressive regimen, prevent early
      rejection and improve prognosis.

PMID- 29343028
TI  - [Pathogenesis of piriformis syndrome: a magnetic resonance imaging-based
      comparison study].
AB  - Objective: To assess the morphological parameters of the piriformis muscle
      through magnetic resonance imaging(MRI) so as to further elucidate the
      pathogenesis of piriformis syndrome (PS). Methods: From September 2015 to October
      2016, 30 suspected PS patients and 30 normal controls were enrolled in this study
      from the Nanfang Hospital, Southern Medical University. The possible causative
      factors of the PS in the patients were obtained, and the PS patients were divided
      into subgroups according to the anatomic site of the tender regions. The
      parameters of the maximum thickness (cm), area (cm(2)) and the volume (cm(3)) of
      the piriformis muscle of both groups were measured by MRI and were statistically
      compared between the groups with the independent-sample t test so as to
      investigate the pathogenesis of injured sciatic nerve. Results: Twenty-six
      patients were verified with PS, unhealthy sitting postures presented in 16
      patients (61.5%) and no trauma history was recorded in these patients. Fifteen
      cases (57.7%) with tenderness located at the suprapiriformis foramen region (SPF
      group, n=15), 11 patients (42.3%) with tenderness at the piriformis muscle (PM
      group, n=11). The thickness, area and volume of the pathological side piriformis
      muscle in the PM group were all significantly higher than the corresponding
      indexes in the control group[(2.24+/-0.46) vs (1.66+/-0.30) cm, (14.4+/-2.2) vs
      (8.8+/-2.1) cm(2,) (23.9+/-3.8) vs (15.2+/-2.6) cm(3,) respectively, t=4.699,
      7.437, 8.291, all P<0.05]and were all higher remarkably than those in the SPF
      group[(1.62+/-0.20) cm, (8.7+/-1.6) cm(2,) (14.1+/-4.8) cm(3,) respectively,
      t=4.640, 7.631, 5.589, all P<0.05]. No significant difference was observed in the
      up-mentioned indexes between the SPF and the control group (t=-0.439, -0.102, 
      1.083, all P>0.05). Conclusions: Tender region at the buttock indicates the
      lesion site in the PS patients. The PS patients with tenderness at the
      suprapiriformis region might originate from another pathogenesis independent of
      piriformis muscle compression, the injury of the sciatic nerve or its branch
      maybe due to the indirect crush by the soft tissue of the suprapiriformis region
      under an unhealthy sitting posture.

PMID- 29343029
TI  - [microRNA targeted to chronic myeloid leukemia Bcr-Abl oncogene screen using
      deacetylase inhibitor].
AB  - Objective: microRNA targeted to chronic myeloid leukemia Bcr-Abl oncogene were
      screened using the deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA).
      Methods: The proliferation inhibition effect of SAHA on chronic myeloid leukemia
      K562 cell was detected by MTS method, and the optimal concentration of SAHA
      reaction was determined. Western blot was used to detect the level of PARP
      protein, and making sure whether SAHA induced apoptosis of K562 cell. Effect of
      SAHA on Bcr-Abl Gene Transcription in K562 Cells was determined by Fluorescence
      Quantitative PCR. The online software Target Scan and real-time fluorescence
      quantitative PCR was used to screen Bcr-Abl-targeted microRNA. The viability of
      K562 cells and Bcr-Abl transcription levels were detected by MTS method and
      quantitative PCR respectively after selected microRNA were transfected into K562
      cell. Results: SAHA significantly inhibited the proliferation of K562 cells and
      induced apoptosis, meanwhile SAHA significantly down-regulated the
      transcriptional level of Bcr-Abl gene. After treatment of K562 cells with SAHA,
      two microRNA, miR-192 and miR-6816, which could target Bcr-Abl, were screened by
      Target Scan and quantitative PCR. Additionally, SAHA induced the miRNAs to up
      regulate 14.5 and 5.2 times, respectively. Transfection of miR-192 and miR-6816
      to K562 cells significantly inhibited K562 cell viability and down-regulated the
      transcriptional level of Bcr-Abl gene. Conclusion: Acetylation inhibitor SAHA
      promoted the expression of miR-192 and miR-6816 in K562 cells by acetylation
      regulation, miR-192 and miR-6816 further down-regulated the transcription of Bcr
      Abl gene, thereby inhibiting K562 cell proliferation and induced apoptosis.

PMID- 29343031
TI  - [Controversy over anticoagulation in patients with pulmonary arterial].

PMID- 29343030
TI  - [Expression of high-mobility group box-I and N-methyl-D-aspartate receptor in
      status epilepticus].
AB  - Objective: To investigate the expression changes of high mobility group box-1
      (HMGB1) and the 2B receptor of N- methyl -D- aspartate receptor (NR2B) in status
      epilepticus (SE). Methods: (1) Primary hippocampal neurons from SD rats with 16
      to 18 days of fetal age were cultured in vitro for 7 days, and exposed to Mg(2+)
      free media for 3 hours. Those cultured neurons were randomly divided into control
      group and intermittent hypoxia group. (2) SD rats with similar weight were
      selected and randomly divided into control group and SE model group. The rat
      model with SE was established by an intraperitoneal injection of lithium chloride
      piloearpine (LI-PILO). Real-time PCR technique was used to detect the expression
      of HMGB1 and NR2B mRNA. Results: In Sombati's cell model cultured in normal
      concentration of oxygen, the HMGB1 mRNA expression levels were 0.005 01+/-0.000
      54, 0.026 76+/-0.003 75, 0.003 52+/-0.000 33, and the NR2B mRNA expression levels
      were 0.008 84+/-0.000 69, 0.012 23+/-0.000 90, 0.029 11+/-0.000 71, respectively,
      at 2, 4 and 6 h; compared with the expressions of HMGB1 and NR2B mRNA at the same
      time points of Sombatis cell model groups, the differences were also significant
      (all P<0.05). After the successful establishment of epilepsy model, the HMGB1
      mRNA expression levels were 0.000 11+/-0.000 09, 0.000 18+/-0.000 01, 0.000 11+/
      0.000 01, and the NR2B mRNA expression levels were 0.196 12+/-0.009 41, 0.232
      11+/-0.006 27, 0.272 48+/-0.005 84, respectively, at 6, 8 and 10 h; compared with
      the expressions of HMGB1 and NR2B mRNA at the same time points of control groups,
      the differences were all significant (all P<0.05). Conclusion: HMGB1 mRNA
      expression levels increase at 2, 4 h, decrease at 6 h in the Sombati's cell model
      in normal oxygen culture, while increase at 6, 8 h, and decrease at 10 h in LI
      PILO induced rat model with SE; the NR2B mRNA relative expression increases with
      time in both the Sombati's cell model in normal oxygen culture and rat model of
      SE.

PMID- 29343032
TI  - [Incidence and short-term outcomes of acute kidney injury in very elderly
      patients].
AB  - Objectives: To study the incidence, clinical characteristics, and prognostic
      impact of acute kidney injury (AKI) in very elderly patients. Methods: The very
      elderly patients (>=75 years) from the Geriatric Department of the Chinese PLA
      General Hospital between January 2007 and December 2015 were retrospectively
      enrolled. AKI was defined according to the 2012 Kidney Disease Improving Global
      Outcomes (KDIGO) criteria. AKI patients were divided into survivor group and non
      survivor group by their outcomes within 90 days after AKI. Prognostic survival
      factors were identified using the Cox proportional hazards regression model.
      Results: In total, 668 geriatric patients (39.0%) developed AKI, and 652 patients
      were included in the final analysis. The median age of the cohort was 87 (84-91)
      years, the majority (623 cases, 95.6%) of whom were male. Among these 652
      patients, 308 (47.2%) had AKI stage 1, 164 (25.2%) had AKI stage 2, and 180
      (27.6%) had AKI stage 3. Of the 652 AKI patients, the 90-day mortality was 33.6%
      (219/652). Multivariate analysis by the Cox model revealed that persistent AKI
      (HR=5.741, 95% CI: 3.356-9.822, P<0.001), more severe AKI stage (stage 2:
      HR=3.363, 95% CI: 1.973-5.732, P<0.001 and stage 3: HR=4.741, 95% CI: 2.807
      8.008, P<0.001), high blood urea nitrogen (BUN) level (HR=1.025, 95% CI: 1.014
      1.037, P<0.001), low body mass index (HR=0.939, 95% CI: 0.897-0.984, P=0.008),
      low mean arterial pressure (MAP) (HR=0.969, 95% CI: 0.959-0.979, P<0.001), low
      prealbumin level (HR=0.935, 95% CI: 0.911-0.959, P<0.001), infection (HR=1.410,
      95% CI: 1.055-1.884, P=0.020), oliguria (HR=1.948, 95% CI: 1.266-2.998, P=0.002)
      were associated with 90-day mortality. Conclusions: The incidence of AKI
      increases significantly with advanced age. More frequent serum creatinine (SCr)
      measurements may be helpful for the early diagnosis of geriatric AKI.
      Identification of risk factors might promote more intensive monitoring and early
      prevention, and thus improve outcomes for very elderly patients with AKI.

PMID- 29343033
TI  - [Clinical features and prognosis of 18 cases of primary lymphocytic
      hypophysitis].
AB  - Objective: To analyze clinical features, prognosis and treatment of lymphocytic
      hypophysitis (LYH). Methods: The clinical data, treatments and outcomes of 18
      cases diagnosed as LYH at Chinese PLA General Hospital between January 2001 and
      July 2017 was respectively reviewed. Results: Eighteen patients with histology
      proven LYH (13 females and 5 males ) were identified. All lymphocytic
      adenohypophysitis (LAH) were females(n=6), two of whom were associated with
      pregnancy. Eleven patients (6 females and 5 males) had lymphocytic
      panhypophysitis (LPH) and one(female) had hypothalamitis. Pre-treatment
      evaluation revealed that 11 patients presented with symptoms of intracranial
      space-occupying lesions, 12 patients had symptoms of anterior pituitary hormone
      deficiencies, and 12 patients had central diabetes insipidus (CDI). All patients
      had space-occupying lesions on magnetic resonance imaging (MRI), which were
      symmetrically enlarged and homogenously enhanced with or without pituitary stalk
      thickening. Before or after surgery, 11 patients received immunosuppressant
      therapy or radiotherapy to alleviate space-occupying effect. After 4-204 months
      follow-up, 5 patients had a relapse and received immunosuppressants, radiotherapy
      or surgery to achieve remission. Full recovery (both symptomatic and
      radiographic) was seen in 6 patients, and 11 patients maintained stable
      replacement therapy. Conclusions: LYH presents with acute space-occupying effects
      such as headache, visual disturbances, hypopituitarism, CDI and mild
      hyperprolactinemia, especially with characteristic radiographic manifestations.
      Usually, surgery reliably establishes diagnosis, and immunosuppressant therapy is
      a necessity. On the whole, LYH has a good prognosis.

PMID- 29343034
TI  - [A study on the effects and safety of sequential humidified high flow nasal
      cannula oxygenation therapy on the COPD patients after extubation].
AB  - Objective: To investigate and compare the effect and safety of nasal high-flow
      oxygen therapy (HFNCO) and noninvasive ventilation (NIV) therapy after extubation
      in patients with chronic obstructive pulmonary disease (COPD). Methods: All COPD
      patients subjected to mechanical ventilation in the Emergency Intensive Unit of
      the First Affiliated Hospital of Zhejiang University during January 2015 to June
      2016 were included in the study. The patients were divided into two groups after
      extubation and HFNCO and NIV were adopted on each group respectively. Clinical
      indexes including the patients' general condition, blood gas analysis and
      pulmonary function before and after extubation, ratio of re-intubation and CT
      grades were collected and analyzed. Results: There was no significant difference
      in the incidence of aspiration (4.8% vs 8.3%), pressure sores (0 vs 8.3%) and
      delirium (4.8% vs 12.5%) between the two groups (all P>0.05). At 12 h after
      extubation, the oxygenation index of NIV group was significantly higher than that
      of the HFNCO group (265+/-29 vs 297+/-33; P<0.05), while no significant
      difference in PCO(2) (P>0.05). For 24 h and 72 h after extubation, there was no
      statistically significant difference in oxygenation index and PCO(2) between the
      both groups (P>0.05). The intensive care unit (ICU) retention time in HFNCO group
      was significantly lower than that in NIV group (13.7+/-0.8 vs 15.2+/-0.5;
      P<0.05). In addition, no significant difference between the two groups in
      mortality and re-intubation rate at 28 d (P>0.05) was observed. Conclusion: HFNCO
      is effective and safe in the treatment of COPD patients after extubation, and it
      is hence valuable for further clinical application.

PMID- 29343035
TI  - [Comparison of percutaneous endoscopic lumbar discectomy versus transforaminal
      lumbar interbody fusion in treating upper lumbar disc herniation].
AB  - Objective: To compare the efficacy of percutaneous endoscopic transforaminal
      discectomy (PTED) and transforaminal lumbar interbody fusion (TLIF) in the
      treatment of high lumbar disc herniation. Methods: The clinical data of patients
      with high lumbar disc herniation from February 2010 to February 2015 were
      retrospective analyzed. According to the inclusion criteria, a total of 63 cases
      were enrolled, including PTED group 33 cases, TLIF group 30 cases. The
      improvement of the two groups before and after surgery was assessed by visual
      analogue scale (VAS) and Oswestry dysfunction index (ODI). The operative time,
      intraoperative blood loss, drainage volume at 48 h postoperatively,
      hospitalization time, number of fluoroscopy, complication, recurrence rate and
      postoperative recovery were compared between the two groups. The follow-up period
      was 12 to 33 months. Results: The operation time, intraoperative blood loss,
      drainage amount and hospitalization time in PTED group were significantly less
      than those in TLIF group[(71+/-19) vs (121+/-22) min, (30+/-21) vs (317+/-50) ml,
      0 vs (93+/-29) ml, (3.5+/-1.9) vs (12.5+/-2.1) d]. The number of fluoroscopy in
      PTED group was significantly higher than TLIF group[(16.2+/-8.3) vs (6.7+/
      4.2)](all P<0.05). There was no significant difference in VAS score and ODI
      improvement rate between the two groups after operation (both P>0.05). There was
      no significant difference between the two groups in the excellent rate of surgery
      and the recurrence rate (both P>0.05). Conclusions: PTED has the advantages of
      less trauma and bleeding, rapid postoperative recovery in the treatment of upper
      lumbar disc herniation compared with TLIF, and the curative effect and recurrence
      rate are similar with TLIF. Therefore, PTED is an effective method for the
      treatment of upper lumbar disc herniation.

PMID- 29343037
TI  - [Mechanisms of fosfomycin resistance of extended-spectrum beta-lactamases
      producing Escherichia coli and Klebsiella pneumoniae].
AB  - Objective: To study the in vitro activity of fosfomycin to extended-spectrum beta
      lactamases (ESBLs)-producing Escherichia coli and Klebsiella pneumoniae and to
      explore the mechanisms of fosfomycin resistance. Methods: A total of 1 052 ESBLs
      producing E. coli(ESBL-EC) and K. pneumoniae(ESBL-KP) isolates were collected
      from bloodstream infections of 28 hospitals of 22 provinces and municipalities,
      which were stored by our laboratory.Minimum inhibitory concentrations (MICs) of
      fosfomycin against these clinical isolates were determined by agar dilution
      methods according to the Clinical and Laboratory Standards Institute
      (CLSI)(2015). The genes related to fosfomycin resistance were confirmed by
      Polymerase Chain Reaction (PCR) and sequencing. Results: The susceptibility rates
      of ESBL-EC and ESBL-KP isolates to fosfomycin were 91.3% (818/896) and 91.7%
      (143/156), respectively. A total of 91 fosfomycin-non-susceptible isolates were
      detected, of which 73 (80.2%) isolates carried fosA3 genes.Amongst 18 fosA3
      negative isolates, 16 isolates were detected to have chromosomal mutations or
      insertion inactivation, while the rest two isolates had not been detected any
      resistant mechanisms. Conclusions: Fosfomycin shows great in vitro antimicrobial
      activity to ESBL-EC and ESBL-KP. The primary mechanism of fosfomycin-non
      susceptible isolates is fosA3 gene.Chromosomal mutations may also involve in the
      fosfomycin resistance.

PMID- 29343036
TI  - [Analysis of genotype and hematological phenotype of 14 patients with
      coinheritance HKalphaalpha and South-East deletion thalassemia].
AB  - Objective: To analyze the genotype-phenotype correlations among those thalassemia
      samples with the presence of -alpha(3.7,) --(SEA) and normal alpha(2) alleles on
      their alpha-globin gene clusters. Methods: Fourteen patients(including 1fetus, 4
      males and 9 females, aged 0- 56 years old)who were suspected diagnosed by
      hematologic analysis and genetic testing among 16 080 participants in our
      laboratory since from August 2011 to August 2016, were enrolled. Complete blood
      cell count was performed on XE4000i automatic hemocyte analyzer. HbA0, HbF and
      HbA2 were tested by high performance liquid chromatography (HPLC). Gap-PCR was
      adopted to detect three common deletional thalassemia deletions. Reverse dot-blot
      (RDB) assay was applied for detecting 17 common beta-globin gene mutations and
      three common non-deletional alpha(2) gene mutations. Two-round nested PCR assay
      was established to detect the genotype of HKalphaalpha in alpha-thalassemia.
      Results: Fourteen cases were identified as HKalphaalpha/--(SEA) (14/16 080),
      including a pedigree and a rare case of HKalphaalpha/--(SEA) co-inheritance with
      IVS-II-654(C->T) heterozygote. In HKalphaalpha/--(SEA) thalassemia group, mean
      cell volume(MCV) was (69.54+/-5.92)fl, and mean cell hemoglobin(MCH) was(22.11+/
      2.22)pg and hemoglobin(Hb) was (117.64+/-18.14) g/L. Compared with normal group,
      MCV, MCH and Hb in HKalphaalpha/--(SEA) thalassemia group, was significantly
      decreased(P<0.05). There were no significant differences between alpha
      thalassemia control group(--(SEA) /alphaalpha) in most hematological parameters
      (P>0.05). Conclusion: The two-round nested PCR could effectively detect the
      HKalphaalpha/--(SEA) genotype. The hematologic characteristics changed
      significantly in HKalphaalpha/--(SEA) group compared with HbH thalassemia and
      normal group. The genotype and phenotype non-correlation in patients with alpha
      thalassemia should especially be causious to avoid a misdiagnosis of genetic
      tests, especially in prenatal diagnosis.

PMID- 29343038
TI  - [Diagnostic value of albumin-bilirubin grade combined with serum ammonia in
      cirrhosis with hepatic encephalopathy].
AB  - Objective: To explore the value of albumin-bilirubin (ALBI) grade combined with
      serum ammonia in the diagnosis of cirrhosis with hepatic encephalopathy (HE).
      Methods: The serum level of total bilirubin(TBIL), albumin( ALB )and blood
      ammonia were detected in 139 patients including 73 cirrhosis patients without HE
      and 66 cirrhosis patients with HE from January 2015 to January 2017 in Beijing
      You'an Hospital, and the relationship between ALBI and blood ammonia value and
      Child grade and hepatic encephalopathy was analyzed. Results: The level of ALBI
      and blood ammonia were more and more higher with the increase of Child grade, the
      level of ALBI in Child A, B and C were -2.3+/-0.6, -1.7+/-0.5, -0.9+/-0.4, and
      there was a statistically significant(F=125.100, P<0.001). The blood ammonia
      concentration in Child A, B and C were(42.6+/-16.0), (56.1+/-31.2), (69.8+/-34.7)
      MUmol/L, and there was a statistically significant(F=7.400, P<0.001). The level
      of ALBI was higher with the increase of model for end-stage liver disease (MELD)
      grade, and there was a positive correlation(r=0.547, P<0.001). The ALBI value in
      the HE group was higher than the cirrhosis patients without HE((-1.1+/-0.5)vs(
      1.6+/-0.7)), and the difference was statistically significant (t=5.244, P<0.001).
      Level of blood ammonia in the HE group was(83.6+/-39.5)MUmol/L, which was higher
      than the level of cirrhosis patients without HE(42.9+/-17.0)MUmol/L, and the
      difference was statistically significant (t=8.130, P<0.001) . When ALBI and blood
      ammonia were combined, the ROC curve area was 0.911, the sensitivity was 93.9%,
      the specificity was 93.2%. Conclusion: There is a significant diagnosis value and
      high clinical application when ALBI is combined with blood ammonia to diagnose HE
      .

PMID- 29343039
TI  - [Development of a Chinese nomogram based on muti-parametric magnetic resonance
      for predicting the probability of prostate cancer in patients after initial
      negative biopsy].
AB  - Objective: To develop a predictive nomogram based on multi-parametric magnetic
      resonance imaging (mpMRI) information to identify men more likely to have a
      cancer diagnosed on repeat prostate biopsy. Methods: The clinical data of 237
      patients who received repeat prostate biopsy after initial negative biopsy from
      Department of Urology of Peking University First Hospital between January 2001
      and August 2016 was reviewed. Patient age, body mass index (BMI), serum total
      prostate-specific antigen (PSA), percent free PSA (f/t), prostate volume (PV),
      PSA density (PSAD), PSA velocity (PSAV), digital rectal examination (DRE),
      transrectal ultrasound (TRUS)and mpMRI results were included in the univariate
      and multivariate analysis. A nomogram was developed using selected variables and
      the area under the receiver operating characteristic (ROC) curve was calculated
      as a measure of discrimination. Results: A total of 76 patients (32.07%) had
      prostate cancer (PCa) detected on repeat biopsy. Based on univariate and
      multivariate logistic regression analysis, the patient age, PSA, PV, DRE and
      mpMRI results were independent predictors for the diagnosis of PCa on repeat
      biopsy. The current nomogram performed well (AUC=0.910) and showed excellent
      calibration. Conclusions: Multi-parametric magnetic resonance imaging combined
      with age, PSA, PV and DRE can predict the probability of PCa in patients with
      initial negative biopsy. The nomogram might help in decision-making for men with
      prior benign histology before the performance of repeat biopsy.

PMID- 29343040
TI  - [Effect of picroside II on the expression of mitochondrial VDAC1 after cerebral
      ischemia/reperfusion in rats].
AB  - Objective: To explore the effect of picroside II on the expression of
      mitochondrial voltage-dependent anion channel 1 (VDAC1) in rats after cerebral
      ischemiareperfusion. Methods: A total of 70 Wistar rats models with middle
      cerebral artery occlusionreperfusion (MCAO/R) were randomly divided into the sham
      group, model group, picroside (Picr) group, ruthenium red (RuR) group, RuR+ Picr
      group, Spermine (Sper) group, Sper+ Picr group (n=10 per group). Modified
      neurological severity scale (mNSS) was used to evaluated the neurobehavioral
      function, the expression of reactive oxygen species (ROS) in brain tissues were
      measured by enzyme-linked immunosorbent assay (ELISA), the morphology of brain
      tissues was observed by hematoxylin-eosin (HE) staining, the apoptotic cells were
      counted by terminal deoxynucleotidyl transferase dUTP nick end labeling assay
      (TUNEL), and the expressions of VDAC1 and endonuclease G (EndoG) were determined
      by immunohistochemical assay and Western blot. Results: Compared with the shame
      group, the mNSS scores (9.6+/-1.9), the expression of ROS[(47.6+/-2.7)U/ml], the
      apoptosis of neuron(23.8+/-2.8), and the expressions of VDAC1(0.94+/-0.06) and
      EndoG in cytoplasm (0.76+/-0.06) and nuclei(0.75+/-0.06)were enhanced in the
      model group (all P<0.05). The Picr group had obviously decreased mNSS scores
      (5.7+/-0.9), ROS expression[(35.6+/-2.2)U/ml], number of apoptotic cells (14.5+/
      2.1), VDAC1 (0.63+/-0.06) and EndoG in cytoplasm (0.34+/-0.05) and nuclei (0.31+/
      0.06)expressions compared to the model group (P<0.05). Conclusion: Picroside II
      could attenuate cerebral I/R injury by down-regulating the expression of VDAC1
      and inhibiting the EndoG release from mitochondria into cytoplasm.

PMID- 29343041
TI  - Forgoing life-sustaining treatments in the ICU. To withhold or to withdraw: is
      that the question?
AB  - In the last decades, mortality from severe acute illnesses has considerably
      declined thanks to the advances in intensive care medicine. Meanwhile, critical
      care physicians realized that life-sustaining treatments (LST) may not be
      appropriate for every patient, and end-of-life care in the Intensive Care Unit
      (ICU) started to receive growing attention. Most deaths occurring in the ICU now
      follow a decision to forgo life-sustaining treatments (DFLST), which can be
      implemented either by withdrawing (WDLST) or withholding (WHLST) life-sustaining
      treatments. Despite the broad consensus about the equivalence of the two
      practices from an ethical point of view, the issue of the best option between
      WDLST and WHLST constantly gives rise to controversies in clinical practice. This
      review is not intended to take a stand for or against WDLST or WHLST. Based on
      available evidence, the definitions of the two practices are first presented.
      Secondly, the preferences of ICU physicians towards WDLST and WHLST are examined.
      Finally, some arguments are offered outlining pros and cons of WDLST and WHLST,
      stressing that the clinician's attention should focus on an early and thorough
      recognition of patients in need of a DFLST, rather than on the theoretical
      strength and weakness of the two practices. This approach will enable physicians
      to make informed decisions on how to implement the limitation of LSTs,
      considering the patients' clinical conditions and preferences, the circumstances
      and needs of their families.

PMID- 29343042
TI  - Harlequin syndrome as a rare complication after epidural anesthesia in an
      obstetric patient.

PMID- 29343043
TI  - Mandibular pain: an uncommon radiation for cervical facet joint syndrome.

PMID- 29343044
TI  - Bronchial blocker positioning: learning curve and confidence in its use.
AB  - BACKGROUND: Despite being simple and safe to use and cheap, EZ blocker (EZB)
      remains underused probably because it requires particular skills in recognizing
      airway and in using fiber-bronchoscopy to check the exact position of their
      cuffs. Thus, we planned an education training program on the use of EZB for
      novices in anesthesia and evaluated the number of procedures required for the
      acquisition of the skills of this technique. METHODS: The educational training
      program included three different phases as follows. The first phase included a
      lecture on the utility of one-lung ventilation in thoracic surgery, on the use of
      the fiber- bronchoscopy and on the characteristics of EZB. The second phase
      consisted in a practical teaching course performed on a manikin model to acquire
      the skills in EZB. The third phase was a clinical training where each participant
      performed a defined number in patients scheduled for thoracic surgery procedures.
      The acquisition of dexterity and satisfaction were then statistically valuated.
      RESULTS: The dexterity in placing EZB significantly increased after six attempts
      (P<0.1). Participants acquired skills in correcting position EZB after 15
      attempts. Participants increased their level of confidence with EZB (score 5.7+/
      1.3) and were highly satisfied with the training received (score 5.8+/-1.6).
      CONCLUSIONS: EZB is a valid strategy for obtaining one lung ventilation. Thus, it
      should be included in the armamentarium of all anesthetists interested in the
      field of thoracic surgery. Our teaching course seems to be a valuable method to
      instill easily and speedily in training novices in anesthesia the skills in
      placing EZB.

PMID- 29343045
TI  - What kind of evidence are we looking for to justify the use of ECCO2R?

PMID- 29343046
TI  - The real role of the PEEP in operating room: pros & cons.

PMID- 29343047
TI  - Acute esophageal necrosis in critically ill patients: consider this possibility!

PMID- 29343048
TI  - Physiology, intervention, and outcome: three critical questions about cerebral
      tissue oxygen saturation monitoring.
AB  - The balance between cerebral tissue oxygen consumption and supply can be
      continuously assessed by cerebral tissue oxygen saturation (SctO2) monitor. A
      construct consisting of three sequential questions, targeting the physiology
      monitored, the intervention implemented, and the outcomes affected, is proposed
      to critically appraise this monitor. The impact of the SctO2-guided care on
      patient outcome was examined through a systematic literature search and meta
      analysis. We concluded that the physiology monitored by SctO2 is robust and
      dynamic, fragile (prone to derangement), and adversely consequential when
      deranged. The inter-individual variability of SctO2 measurement advocates for an
      intervention threshold based on a relative, not absolute, change. The intra
      individual variability has multiple determinants which is the foundation of
      intervention. A variety of therapeutic options are available; however, none are
      100% efficacious in treating cerebral dys-oxygenation. The therapeutic efficacy
      likely depends on both an appropriate differential diagnosis and the functional
      status of the regulatory mechanisms of cerebral blood flow. Meta-analysis based
      on five randomized controlled trials suggested a reduced incidence of early
      postoperative cognitive decline after major surgeries (RR= 0.53; 95% CI: 0.33
      0.87; I2 =82%; P=0.01). However, its effects on other neurocognitive outcomes
      remain unclear. These results need to be interpreted with caution due to the high
      risks of bias. Quality RCTs based on improved intervention protocols and
      standardized outcome assessment are warranted in the future.

PMID- 29343049
TI  - The ultrasound-guided mid-point transverse process to pleura block for
      postoperative analgesia in video-assisted thoracoscopic surgery.

PMID- 29343050
TI  - Phantom limb pain successfully treated with scrambler therapy.

PMID- 29343051
TI  - Ketamine and remote hyperalgesia.

PMID- 29343052
TI  - Implications of oxygenation variations in ventilated patients with respiratory
      infections.

PMID- 29343053
TI  - Staphylococcus aureus producing Panton-Valentine Leukocidin: an emerging problem
      in Italian ICUs.

PMID- 29343054
TI  - Gender and sepsis: first step of personalized medicine?

PMID- 29343055
TI  - Genetically Encoded Circuit for Remote Regulation of Cell Migration by Magnetic
      Fields.
AB  - Magnetoreception can be generally defined as the ability to transduce the effects
      of a magnetic field into a cellular response. Magnetic stimulation at the
      cellular level is particularly attractive due to its ability for deep penetration
      and minimal invasiveness, allowing remote regulation of engineered biological
      processes. Previously, a magnetic-responsive genetic circuit was engineered using
      the transient receptor potential vanilloid 1 (TRPV1) and the iron containing
      ferritin protein (i.e., the TF circuit). In this study, we combined the TF
      circuit with a Ca2+ activated RhoA protein (CaRQ) to allow a magnetic field to
      remotely regulate cell migration. Cells expressing the TF circuit and CaRQ
      exhibited consistent dynamic protrusions, leading to migration along a porous
      membrane, directed spreading in response to a magnetic field gradient, as well as
      wound healing. This work offers a compelling interface for programmable
      electrical devices to control the migration of living systems for potential
      applications in cell-based therapy.

PMID- 29343056
TI  - A Phosphorescent Trinuclear Gold(I) Pyrazolate Chemosensor for Silver Ion
      Detection and Remediation in Aqueous Media.
AB  - We report a phosphorescent chemosensor based on a trinuclear Au(I) pyrazolate
      complex or [Au(3-CH3,5-COOH)Pz]3 (aka Au3Pz3) stabilized in aqueous chitosan (CS)
      polymer media. Au3Pz3 is synthesized in situ within aqueous CS media at pH ~ 6.5
      and room temperature (RT). Au3Pz3 exhibits strong red emission (lambdamax ~ 690
      nm) in such solutions. On addition of silver salt to Au3Pz3/CS aqueous media, a
      bright-green emissive adduct (Au3Pz3/Ag+) with a peak maximum within 475-515 nm
      is developed. The silver adduct exhibits a 4-fold increase in quantum yield (0.19
      +/- 0.02) compared to Au3Pz3 alone (0.05 +/- 0.01), along with a corresponding
      increase in phosphorescence lifetime. With almost zero interference from 15 other
      metal ions tested, Au3Pz3 exhibits extreme selectivity for Ag+ with nM/ppb
      detection limits (6.4-72 ppb, depending on %CS and on the sensitivity basis being
      a signal-to-noise ratio (S/N) = 3 or a baseline-corrected signal change = 10%).
      Au3Pz3 exhibits sensitivity to higher concentrations (>1 mM) of other metal ions
      (Tl+/Pb2+/Gd3+). The sensing methodology is simple, fast, convenient, and can
      even be detected by the naked eye. On addition of ethylenediaminetetraacetic acid
      (EDTA), the red Au3Pz3 emission can be restored. Au3Pz3 and its silver adduct
      retain their characteristic photophysical properties in thin film forms.
      Remarkable photostability with <7% photobleaching after 4 h of UV irradiation is
      attained for Au3Pz3 solutions or thin films.

PMID- 29343057
TI  - Cu-T1 Sensor for Versatile Analysis.
AB  - Conventional magnetic sensors usually employ Fe-based magnetic materials as
      signal probes. In this work, we find that Cu(II) is also a useful longitudinal
      relaxation time (T1) signal-based magnetic probe. We adopt
      bathocuproinedisulfonic acid disodium salt hydrate (BCS) to chelate Cu(I) and
      form a stable Cu(I)-BCS complex in aqueous solution and find the significant
      difference in the T1 value of water protons between Cu(II) aqueous solution and
      Cu(I)-BCS complex aqueous solution. Redox reaction can convert Cu(II) to Cu(I)
      followed by the complexation of BCS, which results in apparent change of T1 that
      can serve as magnetic signal readout, which is the basis of this Cu-T1 sensor.
      Many redox reactions between Cu(II) and Cu(I) allow this Cu-T1 sensor to not only
      realize "one-step mode" assay such as ascorbic acid, protein, and alkaline
      phosphatase but also enable "multi-step mode" immunoassay, such as
      biomacromolecules and small molecules. This Cu-T1 sensor employs Cu ion as signal
      readout, providing an alternative tool for biochemical analysis.

PMID- 29343058
TI  - Biosynthesis of Long-Chain N-Acyl Amide by a Truncated Polyketide Synthase
      Nonribosomal Peptide Synthetase Hybrid Megasynthase in Fungi.
AB  - Truncated iterative polyketide synthase-nonribosomal peptide synthetase (PKS
      NRPS) megasynthases in which only the C domain is present are widespread in
      fungi, yet nearly all members have unknown functions. Bioinformatics analysis
      showed that the C domains of such PKS-C enzymes are noncanonical due to
      substitution at the second histidine in the active site HHxxxDG motif. Here, we
      used genome mining strategy to characterize a cryptic PKS-C hybrid from
      Talaromyces wortmanii and discovered the products are reduced long-chain
      polyketides amidated with a specific omega-amino acid 5-aminopentanoic acid
      (5PA). The wortmanamides resemble long-chain N-acyl-amide signaling lipids that
      target diverse receptors including GPCRs. The noncanonical C domain of this PKS-C
      hybrid was also demonstrated to be a bona fide condensation domain that
      specifically selects 5PA and catalyzes amidation to release polyketide chain.

PMID- 29343059
TI  - Top-Down Characterization of Heavily Modified Histones Using 193 nm Ultraviolet
      Photodissociation Mass Spectrometry.
AB  - The characterization of protein post-translational modifications (PTMs) remains a
      significant challenge for traditional bottom-up proteomics methods owing to the
      lability of PTMs and the difficulty of mapping combinatorial patterns of PTMs
      based on analysis of small peptides. These shortcomings have accelerated interest
      in top-down MS/MS methods that focus on analysis of intact proteins. Simultaneous
      mapping of all PTMs requires extensive sequence coverage to confidently localize
      modifications. 193 nm ultraviolet photodissociation (UVPD) has been shown to
      generate unparalleled sequence coverage for intact proteins compared to
      traditional MS/MS methods. This study focuses on identification and localization
      of PTMs of histones by UVPD, higher-energy collisional dissociation (HCD), and
      the hybrid method electron-transfer/higher-energy collision dissociation (EThcD)
      via a high throughput liquid chromatography-mass spectrometry strategy. In total,
      over 500 proteoforms were characterized among these three activation methods with
      46% of the identifications found in common by two or more activation methods.
      EThcD and UVPD afforded more extensive characterization of proteoforms than HCD
      with average gains in sequence coverage of 15% and C-scores that doubled on
      average.

PMID- 29343060
TI  - Direct CO2 Addition to a Ni(0)-CO Species Allows the Selective Generation of a
      Nickel(II) Carboxylate with Expulsion of CO.
AB  - Addition of CO2 to a low-valent nickel species has been explored with a newly
      designed acriPNP pincer ligand (acriPNP- = 4,5-bis(diisopropylphosphino)-2,7,9,9
      tetramethyl-9H-acridin-10-ide). This is a crucial step in understanding
      biological CO2 conversion to CO found in carbon monoxide dehydrogenase (CODH). A
      four-coordinate nickel(0) state was reliably accessed in the presence of a CO
      ligand, which can be prepared from a stepwise reduction of a cationic
      {(acriPNP)Ni(II)-CO}+ species. All three Ni(II), Ni(I), and Ni(0) monocarbonyl
      species were cleanly isolated and spectroscopically characterized. Addition of
      electrons to the nickel(II) species significantly alters its geometry from square
      planar toward tetrahedral because of the filling of the dx2-y2 orbital.
      Accordingly, the CO ligand position changes from equatorial to axial, ?N-Ni-C of
      176.2(2) degrees  to 129.1(4) degrees , allowing opening of a CO2 binding site.
      Upon addition of CO2 to a nickel(0)-CO species, a nickel(II) carboxylate species
      with a Ni(eta1-CO2-kappaC) moiety was formed and isolated (75%). This reaction
      occurs with the concomitant expulsion of CO(g). This is a unique result markedly
      different from our previous report involving the flexible analogous PNP ligand,
      which revealed the formation of multiple products including a tetrameric cluster
      from the reaction with CO2. Finally, the carbon dioxide conversion to CO at a
      single nickel center is modeled by the successful isolation of all relevant
      intermediates, such as Ni-CO2, Ni-COOH, and Ni-CO.

PMID- 29343061
TI  - Analyzing and Tuning Ribozyme Activity by Deep Sequencing To Modulate Gene
      Expression Level in Mammalian Cells.
AB  - Self-cleaving ribozymes, in combination with aptamers and various classes of
      RNAs, have been heavily engineered to create RNA devices to control gene
      expression. Although understanding of sequence-function relationships of
      ribozymes is critical for such efforts, our current knowledge of self-cleaving
      ribozymes is mostly limited to the results from small scale mutational studies
      performed under different conditions, or qualitative results of mutate-and-select
      experiments that may contain experimental biases. Here, we applied our strategy
      based on deep sequencing to comprehensively assay a large number of mutants to
      systematically examine the effect of the P4 stem sequence on the activity of an
      HDV-like ribozyme. We discovered that the ribozyme activity is highly sensitive
      to the sequence and the apparent stability of the varied positions. Furthermore,
      we demonstrated that the collection of the ribozyme variants with different
      activities can be used as a convenient device to fine-tune the level of gene
      expression in mammalian cells.

PMID- 29343062
TI  - Tailored Waveform of Dielectric Barrier Discharge to Control Composite Thin Film
      Morphology.
AB  - Nanocomposite thin films of TiO2 in a polymer-like matrix are grown in a
      filamentary argon (Ar) dielectric barrier discharge (DBD) from a suspension of
      TiO2 nanoparticles in isopropanol (IPA). The sinusoidal voltage producing the
      plasma is designed to independently control the matrix growth rate and the
      transport of nanoparticle (NP) aggregates to the surface. The useful FSK
      (frequency shift keying) modulation mode is chosen to successively generate two
      sinusoidal voltages: a high frequency of 15 kHz and a low frequency ranging from
      0.5 to 3 kHz. The coating surface coverage by the NPs and the thickness of the
      matrix are measured as a function of the FSK parameters. The duty cycle between
      these two signals is varied from 0 to 100%. It is observed that the matrix
      thickness is mainly controlled by the power of the discharge, which largely
      depends on the high-frequency value. The quantity of NPs deposited in the
      composite thin film is proportional to the duration of the low frequency applied.
      The FSK waveform has a double modulation effect, allowing us to obtain a uniform
      coating as the NPs are not affected by the high frequency and the matrix growth
      rate is limited when the low frequency is applied. When it is close to a
      frequency limit, the low frequency acts like a filter for the NP aggregates. The
      higher the frequency, the smaller the size of the aggregates transferred to the
      surface. By changing only the FSK modulation parameters, the thin film can be
      switched from superhydrophobic to superhydrophilic, and under suitable
      conditions, a nanocomposite thin film is obtained.

PMID- 29343063
TI  - Why Does CuFeS2 Resemble Gold?
AB  - While several potential applications of CuFeS2 quantum dots have already been
      reported, doubts regarding their optical and physical properties persist. In
      particular, it is unclear if the quantum dot material is metallic, a degenerately
      doped semiconductor, or else an intrinsic semiconductor material. Here we examine
      the physical properties of CuFeS2 quantum dots in order to address this issue.
      Specifically, we study the bump that is observed in the optical spectra of these
      quantum dots at ~500 nm. Using a combination of structural and optical
      characterization methods, ultrafast spectroscopy, as well as electronic structure
      calculations, we ascertain that the unusual purple color of CuFeS2 quantum dots
      as well the golden luster of CuFeS2 films arise from the existence of a plasmon
      resonance in these materials. While the presence of free carriers causes this
      material to resemble gold, surface treatments are also described to suppress the
      plasmon resonance altogether.

PMID- 29343064
TI  - Generalized Theory for the Timescale of Molecular Electronic Decoherence in the
      Condensed Phase.
AB  - We introduce a general theory of electronic decoherence for molecules in the
      condensed phase that captures contributions coming from pure dephasing effects,
      electronic transitions among diabatic states, and their interference. The theory
      is constructed by taking advantage of a recently developed [ J. Phys. Chem. Lett.
      2017 , 8 , 4289 - 4294 ] general expression for decoherence times that is based
      on an early time expansion of the purity dynamics and extends early electronic
      decoherence models based on pure dephasing ideas. Using this theory, we construct
      the decoherence time for the displaced harmonic oscillator model amended with
      constant and linear diabatic couplings, which is a widely used model of the
      photoexcited dynamics of molecules. The validity of the short-time expansion is
      demonstrated by the quantitative agreement of the theory with exact numerical
      computations of the decoherence dynamics obtained using the hierarchical equation
      of motion method. These developments offer a rigorous understanding of early time
      electronic decoherence processes that accompany basic molecular events and
      demonstrate that electronic transitions among diabatic states play a major role
      in the decoherence dynamics.

PMID- 29343065
TI  - Perfect Adaptation and Optimal Equilibrium Productivity in a Simple Microbial
      Biofuel Metabolic Pathway Using Dynamic Integral Control.
AB  - The production of complex biomolecules by genetically engineered organisms is one
      of the most promising applications of metabolic engineering and synthetic
      biology. To obtain processes with high productivity, it is therefore crucial to
      design and implement efficient dynamic in vivo regulation strategies. We consider
      here the microbial biofuel production model of Dunlop et al. (2010) for which we
      demonstrate that an antithetic dynamic integral control strategy can achieve
      robust perfect adaptation for the intracellular biofuel concentration in the
      presence of poorly known network parameters and implementation errors in certain
      rate parameters of the controller. We also show that the maximum equilibrium
      extracellular biofuel productivity is fully defined by some of the network
      parameters and, in this respect, it can only be achieved when all the
      corresponding parameters are perfectly known. Since this optimum is a network
      property, it cannot be improved by the use of any controller that measures the
      intracellular biofuel concentration and acts on the production of pump proteins.
      Additional intrinsic fundamental properties for the process are also unveiled,
      the most important ones being the existence of a conservation relation between
      the productivity and the toxicity, a low sensitivity of the optimal productivity
      with respect to a poor implementation of the set-point for the intracellular
      biofuel, and a strong intrinsic robustness property of the optimal productivity
      with respect to poorly known parameters. Taken together, these results
      demonstrate that a high and robust equilibrium rate of production for the
      extracellular biofuel can be achieved when the parameters of the model are poorly
      known and those of the controllers are poorly implemented. Finally, several
      advantages of the proposed dynamic strategy over a static one are also
      emphasized.

PMID- 29343066
TI  - Kane Fermion in a Two-Dimensional pi-Conjugated Bis(iminothiolato)nickel
      Monolayer.
AB  - Massless Kane fermions revealed in zinc-blende semiconductors have recently
      gained interest in the broad study of relativistic materials. In particular, two
      dimensional (2D) Kane fermions were expected to be hybrids of pseudospin-1 and 
      1/2 Dirac fermions. Based on first-principles calculations, we demonstrated that
      2D Kane fermions can be realized in a recently synthesized metal-organic
      framework, namely, bis(iminothiolato)nickel monolayer. A slight compression takes
      the system from a semimetal to a semiconductor. At the critical strain of ~1%,
      the upper and lower conical bands linearize and touch at a single point
      intersecting a flat band, showing the same dispersion as the pseudospin-1 Dirac
      Weyl systems. We adopted a tight-binding Hamiltonian of a line-centered honeycomb
      lattice to reveal the origins and topology of the electronic band structure. The
      coexistence of Kane-type and Dirac-type spectra in the bis(iminothiolato)nickel
      monolayer is expected to benefit the study of multi quasiparticle effects.

PMID- 29343068
TI  - Spotlights: Volume 9, Issue 2.

PMID- 29343067
TI  - Practical Efficiency Limit of Methylammonium Lead Iodide Perovskite (CH3NH3PbI3)
      Solar Cells.

PMID- 29343069
TI  - At the Cutting Edge of Surface Science: A Tribute to Miquel B. Salmeron.

PMID- 29343070
TI  - Autobiography of Miquel B. Salmeron.

PMID- 29343071
TI  - Selected Publications of Miquel B. Salmeron.

PMID- 29343072
TI  - Colleagues of Miquel B. Salmeron.

PMID- 29343073
TI  - Human Semen or Seminal Plasma Does Not Enhance HIV-1BaL Ex Vivo Infection of
      Human Colonic Explants.
AB  - To determine whether human whole semen (WS) and seminal plasma (SP) either
      previously frozen or freshly acquired altered ex vivo infectibility of human
      colonic explants or was associated with histology or toxicity changes, which may
      influence mucosal HIV-1 transmission in vivo. Pooled human semen samples were
      freshly obtained from study volunteers (never frozen) and from commercial sources
      (frozen/thawed). Endoscopically acquired rectal biopsies were evaluated for
      toxicity following titered ex vivo WS/SP exposure by histological grading and by
      MTT assay. The ex vivo HIV-1 biopsy challenge model was used to evaluate effects
      of exposure to either previously frozen or freshly acquired WS/SP on HIVBaL
      infectibility at a range of viral inocula (104-100 TCID50). To evaluate the
      effects at lower viral inocula of HIV-1 (10-2-102), experiments in the presence
      or absence of WS/SP were also performed utilizing TZM-bl cells. MTT assays and
      histological scoring demonstrated no tissue degradation of biopsies when exposed
      for 2 h to concentrations of 10% or 100% of either fresh or previously frozen
      WS/SP. Ex vivo biopsy HIV-1 challenge experiments showed no differences in the
      presence of freshly acquired or previously frozen/thawed WS/SP compared with
      control; no differences were seen with lower infectious titers on TZM-bl cells.
      Within the limits of assay sensitivity and variability, these data show no
      toxicity or significant enhancement of HIV-1 infectibility of human rectal mucosa
      using the colorectal explant model with either pooled fresh or frozen/thawed
      nonautologous human semen.

PMID- 29343074
TI  - Understanding the influence of antipsychotic drugs on global methylation events
      and its relevance in treatment response.
AB  - AIM: The present study intends to evaluate whether antipsychotic drugs can
      modulate the host epigenome and if so whether drug-induced epigenetic modulation
      can explain the heterogeneity in drug response. METHODS: Present study was
      conducted in in vitro cells and significance of these in vitro observations was
      further evaluated in a clinical setting, between drug responsive and
      nonresponsive schizophrenia patients. A number of DNA modifications were assessed
      at global level using 5-methylcytosine, 5-hydroxymethylcytosine and 5
      formylcytosine followed by evaluating the expression of epigenetic modifier genes
      and their crosstalk with miRNAs. RESULTS: In vitro data demonstrated that
      antipsychotic drugs induce epigenetic response by downregulating miRNA that
      target DNA methyltransferases, resulting in global hypermethylation. Similar
      trend was observed in clinical setting too and alterations were markedly
      associated with drug response rather than disease pathogenesis. CONCLUSION: Study
      demonstrates that antipsychotic drugs can influence host methylome and thereby
      indicating its role in mediating a strong pharmacoepigenomic response.

PMID- 29343076
TI  - High Loading Dose of Atorvastatin for the Prevention of Serum Creatinine and
      Cystatin C-Based Contrast-Induced Nephropathy Following Percutaneous Coronary
      Intervention.
AB  - The aim of this study is to assess the efficacy of high-dose atorvastatin on the
      prevention of contrast-induced nephropathy (CIN) in patients with acute coronary
      syndrome (ACS) undergoing percutaneous intervention and observe the incidence of
      cystatin C (CyC)-based CIN. A total of 496 patients with ACS were randomly
      assigned to either the control group (247 patients receiving conventional dose
      atorvastatin 10 mg daily from 1 day before to 3 days after contrast
      administration) or the high-dose atorvastatin group (249 patients receiving
      atorvastatin 40 mg daily for the same perioperative period). The baseline
      characteristics of the 2 groups were similar. The primary end point of serum
      creatinine (SCr)-based CIN occurred in 31 patients in the control group and 16
      patients in the high-dose atorvastatin group (12.6% vs 6.4%; P = .02). Cystatin C
      based CIN developed in 90 patients in the control group and 46 patients in the
      high-dose atorvastatin group (36.4% vs 18.5%; P < .001). A multivariable analysis
      revealed that high-dose atorvastatin was independently associated with a
      decreased risk of CIN. Our study demonstrated that prophylactic treatment with
      high-dose atorvastatin reduced the risk of both SCr and CyC-based CIN and
      suggested that CyC was a more reliable marker for early diagnosis of CIN compared
      with SCr.

PMID- 29343075
TI  - Tocilizumab in Giant Cell Arteritis: A Real-Life Retrospective Study.
AB  - This study aims to evaluate (1) the efficacy and safety of tocilizumab (TCZ) as a
      steroid-sparing agent in patients with giant cell arteritis (GCA) and (2) the
      usefulness of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in
      the follow-up and to detect disease activity. We retrospectively evaluated 12
      patients with GCA treated with TCZ (8 mg/kg/mo). Pre- and posttherapy data about
      clinical signs and symptoms, laboratory results, FDG-PET imaging study, and the
      mean glucocorticoid (GC) dose were used to assess disease activity. Tocilizumab
      achieved complete disease remission in all patients. Mean FDG-PET-detected
      standard uptake value decreased from 2.05 +/- 0.64 to 1.78 +/- 0.45 ( P = .005).
      In 2 patients in whom temporal arteries color Doppler sonography examination was
      consistent with temporal arteritis, the hypoechoic halo disappeared after TCZ
      treatment. Mean GC dose was tapered from 26.6 +/- 13.4 mg/d to 3.3 +/- 3.1 mg/d (
      P < .0001). One-half of the patients discontinued GC therapy. Three patients
      experienced severe adverse reactions and had to stop TCZ therapy. In accordance
      with previous reports, TCZ is an effective steroid-sparing agent for GCA,
      although careful monitoring of adverse drug reactions is needed. 18F
      fluorodeoxyglucose positron emission tomography could be used to monitor disease
      activity in TCZ-treated patients, but prospective studies are needed to confirm
      these data.

PMID- 29343077
TI  - Delayed Onset of Sleep in Adolescents With PAX6 Haploinsufficiency.
AB  - OBJECTIVE: PAX6 haploinsufficiency ( +/-) can occur due to mutations involving
      only PAX6 in patients with isolated aniridia or as contiguous gene deletions in
      patients with Wilms tumor, aniridia, genitourinary anomalies, and range of
      developmental and intellectual disabilities syndrome. Given the role of PAX6 in
      pineal development and circadian regulation, adolescents with PAX6+/- may
      experience sleep-wake disturbances. The purpose of this observational study was
      to explore sleep-related phenotypes in adolescents with PAX6+/-. METHODS: This
      study compared sleep phenotypes of nine subjects with PAX6+/- (aged 10-19 years)
      with previously published data on healthy adolescents ( n = 25, aged 10-18
      years). Subjects completed the Cleveland Adolescent Sleepiness Questionnaire
      (CASQ), Patient Reported Outcomes Measurement Information System (PROMIS) Sleep
      Disturbance (v. 1.0; 8a), and PROMIS Sleep-Related Impairment (v. 1.0; 8b)
      Questionnaires and wore actigraphs for seven nights to record sleep patterns.
      RESULTS: Total CASQ, PROMIS sleep-related impairment, and PROMIS sleep
      disturbance scores were not statistically different between the groups ( ps >
      .15). Actigraph data for lights off to sleep-onset time were found to be
      significantly higher in subjects with PAX6+/- versus the healthy comparison group
      (adjusted mean [95% confidence interval]: 20.1 min [8.1, 49.8] vs. 6.2 min [3.7,
      10.4], respectively, p = .04). CONCLUSION: Both adolescents with PAX6+/- and the
      healthy comparison group on average slept less than 8 hr/night, and overall sleep
      deprivation in adolescents may have masked differences between groups. This study
      used rare genetic disorders with biological vulnerability to sleep problems as a
      genotype-phenotype model. Knowledge of sleep-related phenotypes will assist in
      designing studies to manage sleep-related symptoms in adolescents.

PMID- 29343078
TI  - Quality of life among HIV-infected individuals failing first-line antiretroviral
      therapy in resource-limited settings.
AB  - We evaluated health-related quality of life (QoL) in HIV infection participants
      with virologic failure (VF) on first-line antiretroviral therapy (ART) in 9
      resource-limited settings (RLS). ACTG SF-21 was completed by 512 participants at
      A5273 study entry; 8 domains assessed: general health perceptions (GHP), physical
      functioning (PF), role functioning (RF), social functioning (SF), cognitive
      functioning (CF), pain (P), mental health (MH), and energy/fatigue (E/F); each
      was scored between 0 (worst) to 100 (best). Mean QoL scores ranged from 67 (GHP)
      to 91 (PF, SF, CF). QoL varied by country; high VL and low CD4 were associated
      with worse QoL in most domains, except RF (VL only), SF (CD4 only) and CF
      (neither). Number of comorbidities, BMI and history of AIDS were associated with
      some domains. Relationships between QoL and VL varied among countries for all
      domains. The association of worse disease status with worse QoL may reflect low
      QoL when ART was initiated and/or deterioration associated with VF.

PMID- 29343079
TI  - Cultural factors and oral health-related quality of life among dentate adults:
      Hispanic community health study/study of Latinos.
AB  - OBJECTIVE: Research on the relationships between acculturation, ethnic identity,
      and oral health-related quality of life (OHRQOL) among the U.S. Hispanic/Latino
      population is sparse. The aim of this study is to examine the association between
      acculturation, ethnic identity, and OHRQOL among 13,172 adults in the 2008-2011
      Hispanic Community Health Study/Study of Latinos (HCHS/SOL). DESIGN: Participants
      self-reported their acculturation (immigrant generation, birthplace, residence in
      the U.S., language, and social acculturation), ethnic identity (sense of
      belonging and pride), and four OHRQOL measures. Key socio-demographic,
      behavioral, and oral health outcomes were tested as potential confounders.
      RESULTS: Overall, 57% of individuals experienced poor OHRQOL in at least one of
      the domains examined. In multivariable analyses, some elements of higher
      acculturation were associated with greater food restriction and difficulty doing
      usual jobs/attending school, but not associated with pain or difficulty chewing,
      tasting, or swallowing. While sense of belonging to one's ethnic group was not
      associated with poor OHRQOL, low sense of pride was associated with food
      restriction. Socio-behavioral characteristics were significant effect modifiers.
      CONCLUSION: This study contributes to the understanding of the role of
      Hispanic/Latino's cultural factors in OHRQOL perception and can inform targeted
      strategies to improve OHRQOL in this diverse population.

PMID- 29343080
TI  - Voices from Australia- concerns about HIV associated neurocognitive disorder.
AB  - This study aimed to determine whether people living with HIV (PLHIV) are
      concerned about HIV associated neurocognitive disorder (HAND) and would find
      information and resources for HAND beneficial. An online survey focusing on the
      experience of HAND was distributed via the website of Positive Life New South
      Wales: a peak peer-support non-government organization in Australia. Of 126
      respondents, 94 (74%) had heard of HAND, 52/94 (55%) had experienced concerns and
      of these, 48/52 (92%) felt anxiety about discussing the subject. Of those who had
      experienced concerns, 30/52 (58%) had spoken to someone about these concerns and
      23/30 (77%) had received a positive response. Across the entire sample, 74 (59%)
      had noticed symptoms of cognitive decline in themselves and/or others.
      Respondents who noted a decrease in their ability to organize were on average
      five years older than those who had not noticed a decline (p = 0.012, effect size
      -.54). Forty-nine (39%) indicated that they would like guidance to initiate
      discussion about HAND with their doctor, caregiver or other PLHIV. The survey
      findings suggest that increasing awareness of HAND among PLHIV and their
      caregivers, and providing resources to facilitate discussion about HAND may
      assist to reduce concerns among PLHIV and enhance the effectiveness of clinical
      review.

PMID- 29343081
TI  - Atorvastatin Reduces Plasma Inflammatory and Oxidant Biomarkers in Patients With
      Risk of Atherosclerotic Cardiovascular Disease.
AB  - BACKGROUND: Oxidative stress and inflammation are associated with endothelial
      injury and coronary artery disease. Inflammatory factors that promote oxidative
      damage include endothelin-1 (ET-1), myeloperoxidase (MPO), and C-reactive protein
      (CRP). Current guidelines recommend the use of statins in patients with risk of
      atherosclerotic cardiovascular disease (ASCVD). AIM: To assess the impact of
      atorvastatin on plasma inflammatory and oxidant biomarkers in patients with
      moderate to very high risk of ASCVD. METHOD: Two hundred ten patients presented
      to the cardiology clinic were included and stratified into low, moderate, high,
      and very high risk of ASCVD. Moderate- (20 mg/d) to high-intensity (40 mg/d)
      atorvastatin was prescribed. Plasma levels of lipids, ET-1, CRP, MPO, total
      nitrite, lipid peroxides (thiobarbituric acid reactive substances [TBARS]), and
      superoxide dismutase (SOD) activities were measured at baseline and 12 weeks
      after treatment. RESULT: Relative to low-risk patients, baseline plasma
      inflammatory markers of CRP, MPO, ET-1, and nitrite were higher in patients with
      very high risk of ASCVD, whereas plasma SOD was lower (all P < .05). Use of high
      and moderate atorvastatin therapy significantly reduced low-density lipoprotein
      and total cholesterol levels, as well as plasma levels of CRP, MPO, nitrite, and
      TBARS, and increased plasma SOD activity in patients with moderate to very high
      risk of ASCVD, independent of lipid-lowering effects. CONCLUSIONS: Key markers of
      oxidative stress/inflammation such as CRP, ET-1, total nitrite, and MPO are
      associated with an increased risk of ASCVD. Moderate- and high-intensity
      atorvastatin use reduces plasma oxidative stress and inflammation regardless of
      ASCVD risk and independent of its lipid-lowering effect.

PMID- 29343082
TI  - Systematic Review of the Effect of Adherence to Statin Treatment on Critical
      Cardiovascular Events and Mortality in Primary Prevention.
AB  - AIM: Analyze the relative risks of critical cardiovascular outcomes and mortality
      associated with adherence to statin treatment in a clinical setting in people
      with no history of prior cardiovascular disease (CVD). METHODS: A systematic
      review of the literature was conducted up to December 2016. The outcomes of
      interest were cardiovascular fatal or nonfatal events and all-cause mortality.
      RESULTS: A total of 17 articles were included in a qualitative synthesis. Four
      were case-control nested in a retrospective cohort design and the other 11 were a
      cohort design. Seven studies compared the best adherer patients with the worst
      adherers. In the 3 studies (317 603 participants) that considered ischemic heart
      disease in this group, the pooled reduction in risk was 18% (95% confidence
      interval [CI]: 14%-22%, I2 = 0%); for the CVD outcome, 2 studies (131 477
      participants) showed a pooled reduction in risk of 47% (95% CI: 36%-56%, I2 =
      84.7%) with 1 included study showing a much larger reduction than the others; for
      the cerebrovascular event (CeVD) outcome, 2 studies (155 726 participants) showed
      a pooled reduction in risk of 26% (95% CI: 18%-34%, I2 = 0%); and for mortality,
      the reduction in risk was 49% (95% CI: 39%-57%, I2 = 62.4%). The other 4 studies
      (147 859 participants) compared the most adherent group with the rest. These
      showed a pooled risk reduction of CVD of 22% (95% CI: 6%-27%, I2 = 0).
      CONCLUSION: Adherence to statins treatment is shown as a key element for primary
      prevention, although these are observational data and the risk of bias from
      confounding cannot be ruled out. Standardization of measures of adherence to
      treatment would improve comparability between studies. Further research is
      warranted to design effective interventions to improve patients' adherence.

PMID- 29343083
TI  - Polarized macrophage subsets differentially express the drug efflux transporters
      MRP1 and BCRP, resulting in altered HIV production.
AB  - Introduction Macrophages play an important role in HIV, where they are a cellular
      reservoir. Macrophages are polarized into two phenotypes: pro-inflammatory M1
      macrophages and anti-inflammatory M2 macrophages, which may have altered
      expression of drug efflux transporters, including BCRP and MRP1. These
      differences may result in subtherapeutic concentrations of antiretrovirals inside
      of macrophages and viral replication. Methods U937 and U1 cells were polarized to
      the M1 or M2 phenotype via IFN-gamma and LPS, or IL-4, IL-13, and LPS.
      Transporter expression was assessed via PCR and Western blotting, and transporter
      function was assessed via fluorescent dye assays. Transporter function was
      blocked with the inhibitors MK571 or KO143. Protein expression was confirmed in
      monocyte-derived macrophages. p24 production was assessed in U1 cells via enzyme
      linked immunosorbent assay. Results mRNA and protein analysis demonstrated higher
      expression of MRP1 in M1 macrophages, while BCRP expression was downregulated in
      M1 macrophages. Treatment with inhibitors of transporter function decreased the
      difference in intracellular fluorescence between polarized macrophages.
      Differences in protein expression, which were observed with U937 cells, were
      confirmed in monocyte-derived macrophages. M1, but not M2 cells treated with
      MK571, showed decreased p24 production, consistent with reported MRP1 transporter
      expression. Conclusions These results support our hypothesis that there is
      differential expression of MRP1 and BCRP on M1 and M2 polarized macrophages and
      suggests that these differences may result in altered intracellular
      concentrations of antiretrovirals in macrophages and alter viral production in
      these cells. Targeting these differences may be a strategy to decrease viral
      replication in HIV-infected individuals.

PMID- 29343084
TI  - The correlation analysis of miRNAs and target genes in metastasis of cervical
      squamous cell carcinoma.
AB  - AIM: This study was intended to identify the metastasis-related miRNAs and target
      genes in cervical squamous cell carcinoma. MATERIALS & METHODS: The mRNA and
      miRNA next-generation sequencing data were downloaded. Differential expression
      analysis was carried out, followed by target gene prediction of differentially
      expressed miRNAs. The biological function of differentially expressed genes was
      performed. Validation was carried out by survival analysis and qRT-PCR. RESULTS:
      N4BP3 were associated with the survival time of patients. Hsa-mir-451 and hsa-mir
      486 were related to tumor differentiation stage. Validated expression of hsa-mir
      24-2, hsa-mir-582, NOTCH1, PIP4K2B, DIP2B and IGFBP5 was consistent with the
      bioinformatics analysis. CONCLUSION: Alterations of miRNAs and target genes may
      be useful in understanding the metastasis mechanisms of cervical squamous cell
      carcinoma.

PMID- 29343085
TI  - A Lack of Systemic Absorption Following the Repeated Application of Topical
      Quetiapine in Healthy Adults.
AB  - In the absence of suitable oral or intravenous access for medication
      administration and when the intramuscular medications are undesirable,
      alternative routes for drug delivery may be considered. Antipsychotics
      administered via an inhaled, intranasal, rectal, or topical route have been
      described in the literature. Topically administered antipsychotics have been
      previously reported to produce negligible systemic absorption despite being used
      in clinical practice for nausea and behavioral symptoms associated with dementia.
      Additionally, the American Academy of Hospice and Palliative Medicine recommends
      against the use of topical medications that lack supporting literature. Three
      studies have assessed the systemic absorption of different antipsychotics after
      administration of only a single, topically applied dose. To evaluate whether the
      repeated administration of a topically applied antipsychotic may result in
      detectable serum levels in an accumulating fashion, a pharmacokinetic study was
      conducted. Five healthy, adult participants consented to receive extemporaneously
      prepared topical quetiapine in Lipoderm every 4 hours for a total of 5 doses.
      Blood samples were drawn at baseline and hours 2, 4, 8, 12, 16, and 24, and serum
      quetiapine concentrations were measured using high-performance liquid
      chromatography. Quetiapine was undetectable in every sample from 3 participants.
      Two participants had minimally detectable serum quetiapine levels no sooner than
      hour 12 of the study period. Extemporaneously prepared quetiapine in Lipoderm
      resulted in nonexistent or minimal serum level following repeated topical
      administration. The use of topically applied quetiapine should still be
      questioned.

PMID- 29343086
TI  - Percutaneous Nephrolithotomy and Spina Bifida: Complex Major Stone Surgery?
AB  - BACKGROUND: The incidence of spina bifida (SB) is ~1:1000, and risk of stone
      disease is substantially raised in SB. This is the unique published study of the
      outcome of patients with SB undergoing percutaneous nephrolithotomy (PCNL)
      compared to a neurologically intact historically matched control group at the
      same institution. PATIENTS AND METHOD: A series of 96 PCNLs in 13 SB and 50 non
      SB patients was analyzed. The following measurements were recorded: (1)
      Comorbidities; (2) Preoperative: (renal function, American Society of
      Anesthesiologists [ASA] score); (3) Intraoperative: (anesthesia time, number of
      tracks, stone-free rate); and (4) Postoperative: (sepsis, intensive therapy unit
      and total length of stay, transfusion rate, stone composition, rate of stone
      disease-related nephrectomy). RESULTS: Retrograde access to the ureter was
      impossible in all cases of SB. The median ASA grade (OR 10.5, 95% confidence
      interval [CI] 2.6-42.7) and operative time (median difference 30 minutes, 95% CI
      20-40) were both higher in the SB cohort. Surgeon's estimate of stone-free rate
      was significantly lower in the SB cohort (46% vs 82%). Intensive care requirement
      (0.29 days/PCNL vs 0.1 days/PCNL); total hospital stay (7 days vs 4 days);
      postoperative transfusion rate (11.8% vs 1.6%); and sepsis rate (38% vs 1.6%)
      were all significantly higher in the SB group. Repeat PCNL and nephrectomy for
      recurrent stone disease were both significantly increased in SB cohort compared
      to control group. CONCLUSIONS: PCNL in patients with SB is associated with
      multiple parameters of poor outcome. Patients with SB should be counseled about
      increased peri-operative risk and likelihood of stone recurrence. In an era where
      hospitals are judged according to comparative outcomes, a case may be made for
      comparing PCNL in this cohort of patients separately because of the significantly
      increased peri- and postoperative morbidity.

PMID- 29343087
TI  - Sulfhydrated Sirtuin-1 Increasing Its Deacetylation Activity Is an Essential
      Epigenetics Mechanism of Anti-Atherogenesis by Hydrogen Sulfide.
AB  - AIMS: Hydrogen sulfide (H2S) has a protective role in the pathogenesis of
      atherosclerosis by multiple pathways. Sirtuin-1 (SIRT1) is a histone deacetylase,
      as an essential mediated longevity gene, and has an anti-atherogenic effect by
      regulating the acetylation of some functional proteins. Whether SIRT1 is involved
      in protecting H2S in atherosclerosis and its mechanism remains unclear. RESULTS:
      In ApoE-knockout atherosclerosis mice, treatment with an H2S donor (NaHS or
      GYY4137) reduced atherosclerotic plaque area, macrophage infiltration, aortic
      inflammation, and plasma lipid level. H2S treatment increased aorta and liver
      SIRT1 mRNA expression. Overexpression or slicing cystathionine gamma lyase (CSE)
      also changed intracellular SIRT1 expression. CSE/H2S treatment increased SIRT1
      deacetylation in endothelium and hepatocytes and macrophages, then induced
      deacetylation of its target proteins (P53, P65, and sterol response element
      binding protein), thereby reducing endothelial and macrophage inflammation and
      inhibiting macrophage cholesterol uptake and cholesterol de novo synthesis of
      liver. Also, CSE/H2S induced SIRT1 sulfhydration at its two zinc finger domains,
      increased its zinc ion binding activity to stabilize the alpha-helix structure,
      lowered its ubiquitination, and reduced its degradation. INNOVATION: H2S is a
      novel SIRT1 activator by direct sulfhydration. Because SIRT1 has a role in
      longevity, H2S may be a protector for aging-related diseases. CONCLUSION:
      Endogenous CSE/H2S directly sulfhydrated SIRT1, enhanced SIRT1 binding to zinc
      ion, then promoted its deacetylation activity, and increased SIRT1 stability,
      thus reducing atherosclerotic plaque formation. Antioxid. Redox Signal. 00, 000
      000.

PMID- 29343088
TI  - Creating and testing regulatory focus messages to enhance medication adherence.
AB  - Objectives Strategies were explored to improve patient adherence to
      cardioprotective medications by borrowing from a motivational framework used in
      psychology, regulatory focus theory. The current study is part of a larger
      randomized control trial and was aimed at understanding what written educational
      messages, based on patients' regulatory focus tendency, resonated with each
      individual as a potential reminder to take medications. This study was also aimed
      at understanding why messages resonated with the patients. Methods Twenty
      veterans were tested for regulatory fitand presented with messages dependent on
      focus tendency. In-person semi-structured interviews were conducted to collect
      feedback of messages. An iterative analysis drawing primarily on matrix and
      reflexive team analyses was conducted. Result Six promotion and six prevention
      messages emerged, such as "team up with your provider to create a combination of
      medications to prevent illness" and "Live your best life - Take your
      medications". Five themes related to types of health messages that spoke to
      patients' regulatory fit were discovered: relatability; empowerment and control;
      philosophy on life; relationship with provider and medications; and vocabulary
      effect on the impact of messages. Discussion Motivational messages based on
      regulatory fit may be useful in improving patient medication adherence, leading
      to improved cardiovascular outcomes.

PMID- 29343089
TI  - Peer characteristics associated with improved glycemic control in a randomized
      controlled trial of a reciprocal peer support program for diabetes.
AB  - Objective In a secondary analysis of a randomized controlled trial of diabetes
      reciprocal peer support, we examined characteristics of peers associated with
      improvements in their partner's glycemic control. Methods A total of 102 adults
      with diabetes were randomized to the reciprocal peer support arm (vs. a nurse
      care management arm). The primary outcome was change in A1c over six months.
      Intermediate outcomes were insulin initiation and peer engagement. A number of
      baseline characteristics of peers were hypothesized to influence outcomes for
      their peer, and concordant characteristics of peer dyads were hypothesized that
      would influence outcomes for both peer partners. Results Improvement in A1c was
      associated with having a peer older than oneself ( P < .05) or with higher
      diabetes-related distress ( P < .01). Participants with peers who reported poorer
      health at baseline had worse glycemic control at follow-up ( P < .01).
      Hypothesized concordant characteristics were not associated with A1c
      improvements. Participants whose peers had a more controlled self-regulation
      style were more likely to initiate insulin ( P < .05). Discussion The improved
      outcomes of peers whose partners were older and reported more diabetes distress
      at baseline supports the need for further research into the peer characteristics
      that lead to improved outcomes. This could allow for better matching and more
      effective partnerships.

PMID- 29343090
TI  - Identifying COPD patients at risk for worse symptoms, HRQoL, and self-efficacy: A
      cluster analysis.
AB  - Objectives To identify clusters of chronic obstructive pulmonary disease (COPD)
      patients with distinct beliefs about their illness in terms of symptoms, health
      related quality of life (HRQoL), self-efficacy, and daily life physical activity
      (DLPA). Methods This cross-sectional study included 150 COPD outpatients. The
      patients' illness perceptions, clinical control, HRQoL, self-efficacy, and DLPA
      (accelerometry) were evaluated. A cluster analysis was conducted using data from
      the Illness Perceptions Questionnaire - Revised to establish groups of patients
      with distinct illness perceptions. Differences between clusters were tested using
      a T-test or a Mann-Whitney U test. Results The cluster analysis revealed two
      groups: distressed ( n = 95) and coping ( n = 55). Despite the fact that both
      clusters presented similar pulmonary function, between-cluster differences were
      observed in their self-efficacy, dyspnea, HRQoL, clinical control ( p < 0.001),
      and educational level ( p = 0.002). The levels of DLPA did not differ between the
      clusters. Discussion We observed that clinically stable COPD patients who
      displayed higher emotional representations and less coherence had heightened
      symptoms, poorer HRQoL, worse self-efficacy, and lower educational levels. These
      results emphasize the need to routinely evaluate illness perceptions in COPD
      patients to target and tailor the proper treatment to improve these important
      health outcomes.

PMID- 29343091
TI  - Terminalia chebula supplementation attenuates cisplatin-induced nephrotoxicity in
      Wistar rats through modulation of apoptotic pathway.
AB  - In the present study, we have evaluated the nephroprotective effect of
      hydroalcoholic extract of Terminalia chebula in cisplatin-induced nephrotoxicity
      model. Standardised extract was orally administered to Wistar rats for 10 days at
      different doses. On day 7, 8 mg/kg of cisplatin was administered intra
      peritoneally to rats in all groups. T. chebula, in a dose-dependent manner
      significantly inhibited the elevation of serum creatinine, blood urea nitrogen
      and oxidant stress markers. The immunohistochemical analysis revealed the
      increased levels of apoptotic markers and cytokines in cisplatin group were
      significantly lowered by T. chebula extract. The cisplatin-treated rats kidney
      showed diffused tubular necrosis and infilteration of inflammatory cells which
      was reversed in the treatment group. Chemical characterisation of extract by HPLC
      revealed the presence of corilagin, chebulinic, chebulagic, chebulic, gallic and
      ellagic acid. The findings of this study discovered that T. chebula ameliorated
      oxidative and histological damage caused by cisplatin.

PMID- 29343092
TI  - Health Information at a Global Level: Working to Support the Information Paradox
      Countries.

PMID- 29343093
TI  - Nosology Work: One Step beyond the Medical Record Department.
AB  - This article discusses the role of the nosologist/health information management
      (HIM) professional in a venue one step beyond the hospital's medical record
      department. It provides a glimpse of the role of the HIM professional at a
      statistical government agency, the National Center for Health Statistics (NCHS)
      in the United States, and focuses primarily on the collaborative work that is
      performed by the HIM professional at NCHS. The challenges presented in survey
      coding will be discussed, while practical examples of how we have chosen to
      improve the data collection, data processing and data reporting processes will
      also be addressed.

PMID- 29343094
TI  - Improving Health Records in Developing Countries: The Suriname Experience.

PMID- 29343095
TI  - Health Information Management Practice in Sri Lanka.
AB  - Health information system development in Sri Lanka has generally been a low
      priority. Weaknesses exist in many areas, including vital registration, and
      hospital information such as inpatient and outpatient morbidity and mortality
      data. Lapses in hospital information systems are mainly due to incomplete patient
      medical records; non-availability, inaccuracy and illegibility of the final
      diagnoses on the front sheets; shortage of trained statistical staff; lack of
      supervision at all levels; and lack of facilities at medical record departments.
      WHO's South-East Asian Regional Organization, in collaboration with the
      Australian National Centre in Classification in Health, has developed a group of
      trainers who conduct MR/HIM and ICD-10 training courses within the country.

PMID- 29343097
TI  - Electronic Health Information Management: The Future is Ours to Embrace.

PMID- 29343096
TI  - Estonia's Health Information System and the Digital Health Record.

PMID- 29343098
TI  - Health Information Management Education Programs in Germany.

PMID- 29343099
TI  - Modelling the water-plant cuticular polymer matrix membrane partitioning of
      diverse chemicals in multiple plant species using the support vector machine
      based QSAR approach.
AB  - In this study, a support vector machine (SVM) based multi-species QSAR
      (quantitative structure-activity relationship) model was developed for predicting
      the water-plant cuticular polymer matrix membrane (MX) partition coefficient,
      KMXw of diverse chemicals using two simple molecular descriptors derived from the
      chemical structures and following the OECD guidelines. Accordingly, the
      Lycopersicon esculentum Mill. data were used to construct the QSAR model that was
      externally validated using three other plant species data. The diversity in
      chemical structures and end-points were verified using the Tanimoto similarity
      index and Kruskal-Wallis statistics. The predictive power of the developed QSAR
      model was tested through rigorous validation, deriving a wide series of
      statistical checks. The MLOGP was the most influential descriptor identified by
      the model. The model yielded a correlation (r2) of 0.966 and 0.965 in the
      training and test data arrays. The developed QSAR model also performed well in
      another three plant species (r2 > 0.955). The results suggest the appropriateness
      of the developed model to reliably predict the plant chemical interactions in
      multiple plant species and it can be a useful tool in screening the new chemical
      for environmental risk assessment.

PMID- 29343100
TI  - The Effect of an Orthopedic Hand Surgeon's Attire on Patient Confidence and
      Trust.
AB  - BACKGROUND: Multiple studies have concluded that patients are more likely to
      understand and trust physicians who dress in more formal attire (shirt and tie)
      as opposed to casual attire (t-shirts and jeans). The white coat has repeatedly
      been reported as a major source of trust and confidence in a patient's eyes.
      METHODS: This study explores the effect an orthopedic hand surgeon's attire has
      on a patient's perception of their surgeon's clinical values. All patients 18
      years of age and older who visited our orthopedic hand surgeon's suburban
      outpatient practice were asked to participate in our survey-based study. RESULTS:
      Ninety-seven surveys were completed and included. A majority of our responders
      are female (n = 59, 60.8%), Caucasian (n = 83, 85.6%) between the ages of 55 and
      74 years (n = 40, 41.2%), currently employed (n = 59, 60.8%) with private health
      insurance (n = 69, 71.1%), and married (n = 64, 66.0%). Patients rated male and
      female hand surgeons wearing a white coat highest using the Likert scale and when
      asked about their perceived clinical qualities. Patients consistently poorly
      rated their surgeons wearing casual attire. Patients did note that the white
      coat, or any specific attire, was not necessary during the initial encounter to
      build a strong patient-surgeon relationship. Finally, goatees and beards do not
      positively or negatively impact a surgeon's patient-constructed image.
      CONCLUSIONS: Combining strong clinical skills with appropriate clinical attire
      highlighted by the physician wearing a white coat appears to be an effective way
      to enhance patient satisfaction while ultimately gaining the trust and respect
      needed to properly care for patients.

PMID- 29343102
TI  - The Development of the Philippine Medical Records Association Inc.

PMID- 29343103
TI  - M-Health - Providing Excellence in Quality of Care through Wireless, Telehealth
      and Mobile Technology Integration: Report on the IQPC Conference, Sydney, 30-31
      March 2004.

PMID- 29343101
TI  - MACON: a web tool for computing DNA methylation data obtained by the Illumina
      Infinium Human DNA methylation BeadArray.
AB  - AIM: Bioinformatics analysis for Illumina Infinium Human DNA methylation
      BeadArray is essential, but still remains difficult task for many experimental
      researchers. We here aimed to develop a browser-accessible bioinformatics tool
      for analyzing the BeadArray data. MATERIALS & METHODS: The tool was established
      as an analytical pipeline using R, Perl and Python programming languages.
      RESULTS: We introduced a method that groups neighboring probes into a genomic
      block, which facilitated efficient identification of densely
      methylated/unmethylated regions. The tool, MACON, provided probe filtering, beta
      mixture quantile normalization, grouping into genomic blocks, annotation and
      production of a data subset. CONCLUSION: MACON allows researchers to analyze the
      BeadArray data using a web browser ( http://epigenome.ncc.go.jp/macon ).

PMID- 29343104
TI  - What Do other Organisations Do about Continuing Professional Development?

PMID- 29343105
TI  - The Health IT Rollout: Supporting the End Users.

PMID- 29343106
TI  - Quality of Final Diagnosis Coding in the Medical Records of Selected Hospitals in
      the Colombo District, Sri Lanka.
AB  - Clinical coding is a method of translating a clinical description of a disease or
      procedure into a standard code. Sri Lanka adopted the system of coding
      recommended by the WHO, The International Classification of Diseases - 10th
      Revision (ICD-10), in 1997, and this study was undertaken with the objectives of
      assessing the quality of ICD coding and to identify some factors influencing
      coding quality in this country. A sample of 1091 medical records was selected
      from six hospitals in the Colombo District, representing all categories of
      hospitals in the area. Quality of coding was assessed by using the Australian
      Coding Benchmark Audit (ACBA), a coding quality assessment tool developed by the
      National Centre for Classification in Health, Australia. It was found that the
      availability of the final diagnosis on front sheets of medical records was
      satisfactory (94.7%), but the accuracy of the diagnostic statement was
      unsatisfactory (54%). Out of the six hospitals studied, only the Teaching
      Hospital and the Peripheral Unit practiced coding. The overall rate of accuracy
      of ICD coding in the Colombo District hospitals was 31%, which is unsatisfactory.
      It is recommended that training opportunities in ICD-10 and other related
      subjects should be made available to the coders. Efforts should be made to
      improve the familiarity of the Medical Officers with the WHO guidelines on
      recording diagnostic information for ICD coding.

PMID- 29343107
TI  - Clinical Coders and Decision Making.
AB  - Clinical coders operate at six identifiable levels, which can be described as
      beginner, trainee coder, entry, competent, accredited and advanced levels. In
      this article these levels are elaborated within the theoretical perspectives of
      Simon's four-stage and Wilson and Walsh's six-stage models of systematic decision
      making. The article then examines briefly the importance of understanding how
      clinical coders make decisions, because of both the coder's crucial role in
      determining hospital funding, and the reliance of research upon access to
      accurate data. Finally, future avenues for study in this area are suggested.

PMID- 29343108
TI  - Health Information Management: An International Focus.

PMID- 29343109
TI  - Preparing for the New Information Environment.

PMID- 29343110
TI  - Can the physical environment itself influence neurological patient activity?
AB  - PURPOSE: To evaluate if a changed physical environment following redesign of a
      hospital ward influenced neurological patient physical and social activity.
      METHODS: A "before and after" observational design was used that included 17
      acute neurological patients pre-move (median age 77 (IQR 69-85) years Ward A and
      20 post-move (median age 70 (IQR 57-81) years Ward B. Observations occurred for 1
      day from 08.00-17.00 using Behavioral Mapping of patient physical and social
      activity, and location of that activity. Staff and ward policies remained
      unchanged throughout. An Environmental Description Checklist of each ward was
      also completed. RESULTS: Behavioral Mapping was conducted pre-/post-move with a
      total of 801 Ward A and 918 Ward B observations. Environmental Description
      Checklists showed similarities in design features in both neurological wards with
      similar numbers of de-centralized nursing stations, however there were more
      single rooms and varied locations to congregate in Ward B (30% more single
      patient rooms and separate allied health therapy room). Patients were alone >60%
      of time in both wards, although there was more in bed social activity in Ward A
      and more out of bed social activity in Ward B. There were low amounts of physical
      activity outside of patient rooms in both wards. Significantly more physical
      activity occurred in Ward B patient rooms (median = 47%, IQR 14-74%) compared to
      Ward A (median = 2% IQR 0-14%), Wilcoxon Rank Sum test z = -3.28, p = 0.001.
      CONCLUSIONS: Overall, patient social and physical activity was low, with little
      to no use of communal spaces. However we found more physical activity in patient
      rooms in the Ward B environment. Given the potential for patient activity to
      drive brain reorganization and repair, the physical environment should be
      considered an active factor in neurological rehabilitation and recovery.
      Implications for Rehabilitation Clinicians should include consideration of the
      impact of physical environment on physical and social activity of neurological
      patients when designing therapeutic rehabilitation environments. Despite
      architectural design intentions patient and social activity opportunities can be
      limited. Optimal neurological patient neuroplasticity and recovery requires
      sufficient environmental challenge, however current hospital environments for
      rehabilitation do not provide this.

PMID- 29343111
TI  - Getting the Most from Routinely Collected Data.

PMID- 29343112
TI  - Eight Methods for Improving Coding Quality and Efficiency.

PMID- 29343113
TI  - Ninth National Centre for Classification in Health Conference. 16-18 March 2005.
      Perth, Western Australia.

PMID- 29343114
TI  - Governance and Our Organisation.

PMID- 29343115
TI  - Health Informatics and Health Professionals.

PMID- 29343116
TI  - Challenges in Coding and Classification.

PMID- 29343117
TI  - 25th National Conference, Health Information Management Association of Australia.
      Geelong, July 2005. Conference Discharge Summary.

PMID- 29343118
TI  - Coding Rules! Ninth National Centre for Classification in Health Conference. 16
      18 March 2005. Perth, Western Australia.

PMID- 29343119
TI  - Electronic Health Records: Security, Safety and Archiving.

PMID- 29343120
TI  - An update on the advancing high-throughput screening techniques for patch clamp
      based ion channel screens: implications for drug discovery.
AB  - INTRODUCTION: Automated patch clamp (APC) devices have become commonplace in many
      industrial and academic labs. Their ease-of-use and flexibility have ensured that
      users can perform routine screening experiments and complex kinetic experiments
      on the same device without the need for months of training and experience. APC
      devices are being developed to increase throughput and flexibility. Areas
      covered: Experimental options such as temperature control, internal solution
      exchange and current clamp have been available on some APC devices for some time,
      and are being introduced on other devices. A comprehensive review of the
      literature pertaining to these features for the Patchliner, QPatch and Qube and
      data for these features for the SyncroPatch 384/768PE, is given. In addition,
      novel features such as dynamic clamp on the Patchliner and light stimulation of
      action potentials using channelrhodosin-2 is discussed. Expert opinion: APC
      devices will continue to play an important role in drug discovery. The
      instruments will be continually developed to meet the needs of HTS laboratories
      and for basic research. The use of stem cells and recordings in current clamp
      mode will increase, as will the development of complex add-ons such as dynamic
      clamp and optical stimulation on high throughput devices.

PMID- 29343121
TI  - Health Data Standards Committee Meeting Report.

PMID- 29343122
TI  - Use of the Godin leisure-time exercise questionnaire in multiple sclerosis
      research: a comprehensive narrative review.
AB  - PURPOSE: The Godin Leisure-Time Exercise Questionnaire has been a commonly
      applied measure of physical activity in research among persons with multiple
      sclerosis over the past decade. This paper provides a comprehensive description
      of its application and inclusion in research on physical activity in multiple
      sclerosis. METHOD: This comprehensive, narrative review included papers that were
      published between 1985 and 2017, written in English, involved participants with
      multiple sclerosis as a primary population, measured physical activity, and cited
      one of the two original Godin papers. RESULTS AND CONCLUSION: There is a broad
      scope of research that has included the Godin Leisure-Time Exercise Questionnaire
      in persons with multiple sclerosis. Overall, 8 papers evaluated its psychometric
      properties, 21 evaluated patterns of physical activity, 24 evaluated correlates
      or determinants of physical activity, 28 evaluated outcomes or consequences of
      physical activity, and 15 evaluated physical activity interventions. The Godin
      Leisure-Time Exercise Questionnaire is a valid self-report measure of physical
      activity in persons with multiple sclerosis, and further is an appropriate,
      simple, and effective tool for describing patterns of physical activity,
      examining correlates and outcomes of physical activity, and provides a sensitive
      outcome for measuring change in physical activity after an intervention.
      Implications for rehabilitation There is increasing interest in physical activity
      and its benefits in multiple sclerosis. The study of physical activity requires
      appropriate and standardized measures. The Godin Leisure-Time Exercise
      Questionnaire is a common self-report measure of physical activity for persons
      with multiple sclerosis. Godin Leisure-Time Exercise Questionnaire scores are
      reliable measures of physical activity in persons with multiple sclerosis. The
      Godin Leisure-Time Exercise Questionnaire further is an appropriate, simple, and
      effective tool for describing patterns of physical activity, examining correlates
      and outcomes of physical activity participation, and is an advantageous primary
      outcome for measuring change in physical activity in response to an intervention.

PMID- 29343124
TI  - Health Information Management in Epidemiological Research.

PMID- 29343123
TI  - Ninth National Centre for Classification in Health Conference. 16-18 March 2005.
      Perth, Western Australia.

PMID- 29343125
TI  - The changing pattern and determinants of declining consanguinity in Jordan during
      1990-2012.
AB  - BACKGROUND: Consanguinity is a deep rooted cultural trait in Jordan. AIM: To
      examine the patterns and determinants of declining rates of consanguineous
      marriage in Jordan during 1990-2012 in the context of the changing pattern of
      socio-economic and demographic conditions. MATERIALS AND METHODS: The data come
      from the 1990 and 2012 Jordan Population and Family Health Surveys (JPFHSs). A
      total of 6461 women in 1990 and 11,352 women in 2012 were successfully
      interviewed. Descriptive and multivariate statistical techniques were used for
      data analysis. RESULTS: Consanguinity was found to be widely practiced (35% in
      2012) until recent times in Jordan. However, there has been a secular declining
      trend over the last few decades as the practice of consanguinity has declined
      from 56% in 1990 to 35% in 2012. Increasing age at marriage and female education,
      higher level of education of husbands, declining family size, increasing rate of
      urbanisation and female employment, exposure to mass media and higher economic
      status appeared as significant predictors of declining consanguinity in Jordan.
      CONCLUSIONS: The findings of this study support Goode's hypothesis of a decrease
      of consanguinity with modernisation. Although consanguinity is a deeply rooted
      cultural trend in Jordan, it is gradually losing ground due to modernisation and
      socio-demographic transition of the country.

PMID- 29343126
TI  - Challenges in Coding and Classification.

PMID- 29343128
TI  - Efficacy and safety of flexibly dosed brexpiprazole for the adjunctive treatment
      of major depressive disorder: a randomized, active-referenced, placebo-controlled
      study.
AB  - OBJECTIVE: To assess the efficacy, safety, and tolerability of brexpiprazole as
      adjunctive treatment in adults with major depressive disorder (MDD) and an
      inadequate response to prior antidepressant treatment (ADT). METHODS: Patients
      with a current major depressive episode after prior treatment with 1-3 ADTs
      entered an 8- or 10-week prospective treatment phase in which they received
      double-blind placebo adjunct to open-label ADT. Inadequate responders were
      randomized (2:2:1) to brexpiprazole 2-3 mg/day, placebo, or quetiapine extended
      release (XR) 150-300 mg/day, adjunct to the same ADT, for 6 weeks. The primary
      efficacy endpoint was the change from baseline (randomization) to week 6 in
      Montgomery-Asberg Depression Rating Scale (MADRS) total score. The key secondary
      efficacy endpoint was the change in Sheehan Disability Scale (SDS) mean score.
      RESULTS: Adjunctive brexpiprazole showed a greater improvement in MADRS total
      score than adjunctive placebo (least squares mean difference [95% confidence
      interval] = -1.48 [-2.56, -0.39]; p = .0078), whereas adjunctive quetiapine XR
      did not separate from placebo (-0.30 [-1.63, 1.04]; p = .66). Adjunctive
      brexpiprazole failed to separate from placebo on the SDS mean score (-0.23 [
      0.52, 0.07]; p = .13), but did improve functioning on two of the three SDS items
      (family life and social life). The most frequent treatment-emergent adverse
      events in patients receiving brexpiprazole were akathisia (6.1%), somnolence
      (5.6%), and headache (5.6%). CONCLUSIONS: Adjunctive brexpiprazole 2-3 mg/day
      improved symptoms of depression compared with adjunctive placebo in patients with
      MDD and an inadequate response to ADTs, and was well tolerated with no unexpected
      side effects.

PMID- 29343129
TI  - Major Achievement by Associate Professor Johanna Westbrook: Election to the
      American College of Medical Informatics as an International Fellow.
AB  - Congratulations to Associate Professor Johanna Westbrook PhD, MHA, GradDipAppEpi,
      BAppSc (Medical Record Administration), who has been elected to the American
      College of Medical Informatics as an International Fellow. The Fellowship is the
      highest recognition possible in the health informatics discipline. Based upon
      peer election from current College Fellows, no more than two Fellowships are
      offered in any one year, and there are currently only two other Australian
      Fellows. This is a wonderful honour as it marks the highest peer recognition
      possible from the international community, reflecting Johanna's outstanding
      research work. Johanna is currently Deputy Director of the Centre for Health
      Informatics at the University of New South Wales and is an honorary Associate
      Professor at the School of Health Information Management at the University of
      Sydney. Johanna has published over 80 refereed journal articles and has received
      numerous research grants, the most recent of which is a National Health and
      Medical Research Council Project Grant of $583 000 for a study investigating the
      safety and effectiveness of hospital e-prescribing systems.

PMID- 29343130
TI  - A community-based exercise program to increase participation in physical
      activities among youth with disability: a feasibility study.
AB  - PURPOSE: To evaluate the feasibility of a student-mentored community-based
      exercise program for youth with disability. METHOD: Nineteen youth (nine female;
      mean age 18 years) with disability (seven cerebral palsy, six Down syndrome,
      three spina bifida, two autism spectrum disorder, one spinal cord injury) were
      recruited. Each participant was matched with a student mentor and exercised twice
      a week for 12 weeks at their local gymnasium. Five domains of feasibility were
      assessed: demand, implementation, practicality, limited efficacy testing, and
      acceptability. RESULTS: Demand comprised 55 expressions of interest.
      Demonstrating evidence of implementation, 91% of scheduled sessions were attended
      and training fidelity (comparing training load in weeks 1 and 12) showed exercise
      intensity significantly increased for strength and aerobic exercises. The program
      was practical with no major and 17 minor adverse events (e.g., muscle soreness).
      Limited efficacy testing was demonstrated by increased arm (4 kg, 95% CI: 1-7)
      and leg strength (43 kg, 95% CI: 24-62), walking endurance (80 m, 95% CI: 24
      137), and improvement in three dimensions of health-related quality of life
      (autonomy, physical, and psychological well-being). The program was accepted very
      positively by participants. CONCLUSIONS: A student-mentored community-based
      exercise program feasibly engages youth with disability in community-based
      exercise. Implications for Rehabilitation A 12-week community-based student
      mentored exercise program for youth with disability is feasible. Exercising in a
      real-world setting with a student mentor has a positive effect on physical and
      psychological well-being of youth with disability.

PMID- 29343131
TI  - Safety and tolerability of plecanatide in patients with chronic idiopathic
      constipation: long-term evidence from an open-label study.
AB  - OBJECTIVE: This multi-center, fixed-dose, open-label study evaluated the long
      term safety and tolerability of once-daily oral plecanatide for the treatment of
      adults with chronic idiopathic constipation (CIC). METHODS: Eligible patients
      completed a phase 2b or phase 3 double-blind study of plecanatide, or had not
      previously been treated with plecanatide. Enrolled patients received plecanatide
      (3 or 6 mg) for up to 72 weeks. Safety and tolerability were assessed by the
      incidence, nature, and severity of spontaneously reported treatment-emergent
      adverse events (TEAEs). Patients also completed Patient Global Assessment
      questionnaires, which included measures of treatment satisfaction and the desire
      to continue treatment. RESULTS: There were 2370 patient exposures in this study,
      with the vast majority (90.5%) receiving treatment with plecanatide 6 mg. At the
      time of study closure, 1932 (81.5%) had completed or were still receiving study
      drug. TEAEs were qualitatively and quantitatively similar to those observed in
      prior double-blind studies. The most common TEAEs were diarrhea (7.1%) and
      urinary tract infection (2.2%). TEAEs leading to discontinuation occurred in 5.3%
      of patients, with diarrhea leading to discontinuation in 3.1%. Most TEAEs were
      mild/moderate in severity and were generally considered not related to
      plecanatide treatment. At the end of treatment, the median score for treatment
      satisfaction was 4.0 (quite satisfied), and the median score for treatment
      continuation was 4.0 (quite likely). CONCLUSIONS: Long-term treatment of adults
      with CIC demonstrated that plecanatide was safe and well tolerated, with low TEAE
      and discontinuation rates. Patients indicated satisfaction and a desire to
      continue with plecanatide treatment.

PMID- 29343132
TI  - IT14/2 Semantic Interoperability Meeting Report 20 February 2006.

PMID- 29343133
TI  - Central nervous system malformation associated with methamphetamine abuse during
      pregnancy.
AB  - INTRODUCTION: Prenatal methamphetamine exposure is related to prematurity, fetal
      growth restriction, neurobehavioral effects and long-term motor and cognitive
      sequelae. PATIENT PRESENTATION: We report the case of a newborn from a Filipina
      with no prenatal care with a complex brain malformation. Methamphetamine was
      identified in maternal and neonatal urine and in maternal hair, raising our
      suspicion of methamphetamine as a cause of this malformation. DISCUSSION:
      Methamphetamine abuse is a growing problem worldwide. There are little data on
      its effect on the fetus. To our knowledge, no fetal brain abnormalities have been
      associated with its use. In our case, the lack of antenatal control does not
      allow us to date when this malformation appeared. CONCLUSION: The aim of our
      report is to generate awareness of the possible association between
      methamphetamine abuse during pregnancy and central nervous system malformations.

PMID- 29343134
TI  - Implementation of vaginal cleansing prior to cesarean delivery to decrease
      endometritis rates.
AB  - BACKGROUND: Endometritis is a postpartum complication that is more common after
      cesarean delivery. It frequently requires intravenous antibiotic administration,
      prolonged hospital stays, and carries a risk of sepsis or abscess formation.
      Precesarean vaginal preparation has been shown to decrease the risk of
      endometritis in patients who have labored or have ruptured membranes. OBJECTIVE:
      The objective of this study was to assess the practical implementation of a
      protocol for vaginal cleansing prior to cesarean delivery and the subsequent
      effect on endometritis rates in a clinical setting. STUDY DESIGN: This is a
      before-after retrospective cohort study evaluating the first 6 months of
      implementation of a vaginal cleansing protocol at a single institution. The
      primary outcome was the rate of implementation. Secondary outcomes included
      endometritis and other postoperative complications. RESULTS: The rate of
      implementation after 6 months was 68.3% (p < .001) and postoperative endometritis
      rates decreased from 14.0% before implementation to 11.7% after implementation (p
      .49, OR 0.77, CI 0.36-1.62). Postoperative fever decreased from 22.3% to 18.3% (p
      .256, OR 0.70, CI 0.37-1.30) and infectious wound complications were 4.5% and
      5.8%, respectively (p .76, OR 1.07, CI 0.69-3.64). CONCLUSIONS: Implementation of
      a protocol for vaginal cleansing prior to cesarean delivery in women with
      ruptured membranes or in labor has high uptake, but in almost a third of eligible
      women it was not performed. The implementation, has led to a clinical, although
      not statistical, decrease in postoperative endometritis. Continued research is
      needed to explore how to improve uptake of this quality improvement measure.

PMID- 29343135
TI  - Genetic polymorphisms in folate metabolism as risk for Down syndrome in the
      southern China.
AB  - OBJECTIVE: To assess the association between maternal gene polymorphisms of the
      enzymes involved in folate metabolism and the risk of having a Down syndrome (DS)
      offspring in southern China mothers. METHODS: Gene polymorphisms in folate
      metabolizing and the levels of homocysteine (HCY) were analyzed in 84 southern
      China mothers with DS babies (the case group) and 120 healthy mothers (the
      control group). Methylenetetrahydrofolate reductase (MTHFR) C677T (rs1801133) and
      A1298C (rs1801131), methionine synthase (MTR) A2756G (rs1805087), and methionine
      synthase reductase (MTRR) A66G (rs1801394) were studied. RESULTS: We found no
      significant differences (p > .05) in the frequencies of four genetic
      polymorphisms between the two groups. We found gene-gene interactions had a 1.997
      fold increased risk in MTHFR 677 CT with MTR AA (OR: 1.997, 95% CI: 1.038-3.841,
      p = .038) and a 2.588-fold increased risk in MTHFR 677 CT with MTRR AG (OR:
      2.588, 95% CI: 1.111-6.031, p = .028) in the case group than control. The levels
      of HCY were significantly higher in MTHFR 677 TT than MTHFR 677 CC in the case
      group (TT 17.2167+/-5.1051, CC 12.1969+/-5.0299, F = 2.194, p < .05), and it was
      significantly higher in MTHFR 677 TT in the case group than control (TT 17.2167+/
      5.1051 in the case group, TT 10.2286+/-1.4373 in the control group, F = 2.546, p
      < .05). CONCLUSION: These results suggest that genetic polymorphisms involved in
      folate metabolism may have population specificity in determining the
      susceptibility of having DS offsprings. The gene-nutrition, gene-gene
      interactions and ethnicity are important variables to be considered in
      periconceptional nutritional supplementation and antenatal care for reducing the
      risk of DS babies.

PMID- 29343136
TI  - Heme oxygenase activity increases after exercise in healthy volunteers.
AB  - Heme oxygenase (HO) is an essential, rate-limiting protein which catalyses the
      breakdown of heme to iron, carbon monoxide (CO), and biliverdin. The alpha
      methene bridge of the heme is eliminated as CO which can be measured as blood
      carboxyhaemoglobin (COHb). Using blood concentrations of COHb as a measure
      reflecting HO activity, we tested the postulate that the activity of HO changes
      with exercise. Ten healthy, nonsmoking volunteers (5 females and 5 males with a
      mean age +/- standard deviation of 25.7 +/- 3.2 years), lifetime nonsmokers with
      no history of respiratory diseases and not taking any medication, were included
      in the study. Subjects were exposed to filtered air for 2 hrs while alternating
      exercise for 15 minutes on a cycle ergometer with rest for 15 minutes. Workload
      was adjusted so that subjects breathed at a ventilatory rate, normalised for body
      surface area, of 25 L/m2/minute. Immediately before, immediately after, and the
      day following exercise, blood was drawn by standard venipuncture technique. COHb
      was determined using the interleukin (IL) 682 Co-Oximeter (Instrumentation
      Laboratory, Bedford, MA). COHb increased in each participant during the exercise
      session with the mean value (+/- standard deviation) almost doubling (1.1 +/- 1.6
      to 2.1 +/- 1.6%) and returned to baseline by the following day (1.3 +/- 1.3%). We
      conclude that exercise increases HO activity.

PMID- 29343137
TI  - Hybrid aortic arch and frozen elephant trunk reconstruction: bridging the gap
      between conventional and total endovascular arch repair.
AB  - INTRODUCTION: Novel endovascular techniques hope to offer patients aortic arch
      repair with reduced morbidity compared to conventional arch surgery; however,
      current endovascular strategies remain challenged by the proximal seal zone,
      higher stroke rates, long-term durability and select anatomy. Hybrid arch repair
      offers patients a less invasive alternative that can treat more distal aorta than
      conventional arch repair yet still be performed via standard sternotomy. Areas
      covered: This review will discuss the current evidence and future development of
      hybrid aortic arch and frozen elephant trunk reconstruction. Several approaches
      to hybrid arch repair are summarized, including the off-label use of thoracic
      endovascular stent-grafts and commercially manufactured hybrid grafts. Technical
      considerations and clinical outcomes with each approach will be addressed along
      with advantages and disadvantages. Expert commentary: Hybrid arch repair will
      undergo continued refinement as our ability to provide a less-invasive
      alternative to conventional open arch repair grows. Evolution to allow for
      improved head vessel branch sizing, improved frozen elephant trunk deployment
      accuracy, monitoring to prevent paraplegia and utilization of intraoperative
      image guidance in hybrid operating rooms is necessary. The potential exists for
      hybrid approaches to arch pathology to completely supplant conventional surgery,
      while avoiding the potential deleterious complications of total endovascular
      repair.

PMID- 29343138
TI  - The efficacy of myo-inositol supplementation to prevent gestational diabetes
      onset: a meta-analysis of randomized controlled trials.
AB  - INTRODUCTION: The efficacy of myo-inositol supplementation to prevent gestational
      diabetes onset remains controversial. We conducted a systematic review and meta
      analysis to explore the influence of myo-inositol supplementation on the
      incidence of gestational diabetes. METHODS: We search PubMed, Embase, Web of
      science, EBSCO, and Cochrane Library databases through November 2017 for
      randomized controlled trials (RCTs) assessing the effect of myo-inositol
      supplementation on gestational diabetes onset. This meta-analysis is performed
      using the random-effect model. RESULTS: Five randomized controlled trials (RCTs)
      are included in the meta-analysis. Compared with control group in pregnant women,
      myo-inositol supplementation is associated with significantly reduced incidence
      of gestational diabetes (risk ratio (RR) = 0.43; 95%CI = 0.21-0.89; p = .02), and
      preterm delivery (RR = 0.36; 95%CI = 0.17-0.73; p = .005), but has no substantial
      impact on 2-h glucose oral glucose tolerance test (OGTT) (mean difference (MD) = 
      6.90; 95%CI = -15.07 to 1.27; p = .10), gestational age at birth (MD = 0.74;
      95%CI = -1.06 to 2.54; p = .42), birth weight (MD = -5.50; 95%CI = -116.99 to
      105.99; p = .92), and macrosomia (RR = 0.65; 95%CI = 0.20-2.11; p = .47).
      CONCLUSIONS: Myo-inositol supplementation has some ability to reduce the
      incidence of gestational diabetes and preterm delivery in pregnant women.

PMID- 29343139
TI  - The impact of medical school assessment on preparedness for practice.
AB  - PURPOSE: As assessment is known to drive learning, this paper looks at the
      relationship between assessment practice across UK medical schools and graduates
      preparedness for practice. MATERIALS AND METHODS: It uses data on written and
      practical assessment at each medical school and the association with students'
      self-reported preparedness for working as a foundation doctor on graduation, and
      in particular the preparation related to clinical skills. RESULTS AND
      CONCLUSIONS: A negative correlation (beta= -0.003, p < 0.001) was observed
      between total duration of written assessment and preparedness, while a positive
      relationship (beta = 0.461, p < 0.001) was seen between "adequately prepared" and
      the proportion of all assessment time focusing on practical skills. This suggests
      that graduates from medical schools with a greater emphasis on practical skills
      in their assessment plan are better prepared to practice as a junior doctor on
      gradation; something that may be of relevance when designing a national licensing
      examination.

PMID- 29343140
TI  - A heterogeneous tissue model for treatment planning for magnetic resonance-guided
      laser interstitial thermal therapy.
AB  - We evaluated a physics-based model for planning for magnetic resonance-guided
      laser interstitial thermal therapy for focal brain lesions. Linear superposition
      of analytical point source solutions to the steady-state Pennes bioheat transfer
      equation simulates laser-induced heating in brain tissue. The line integral of
      the photon attenuation from the laser source enables computation of the laser
      interaction with heterogeneous tissue. Magnetic resonance thermometry data sets
      (n = 31) were used to calibrate and retrospectively validate the model's thermal
      ablation prediction accuracy, which was quantified by the Dice similarity
      coefficient (DSC) between model-predicted and measured ablation regions (T > 57 
      degrees C). A Gaussian mixture model was used to identify independent tissue
      labels on pre-treatment anatomical magnetic resonance images. The tissue
      dependent optical attenuation coefficients within these labels were calibrated
      using an interior point method that maximises DSC agreement with thermometry. The
      distribution of calibrated tissue properties formed a population model for our
      patient cohort. Model prediction accuracy was cross-validated using the
      population mean of the calibrated tissue properties. A homogeneous tissue model
      was used as a reference control. The median DSC values in cross-validation were
      0.829 for the homogeneous model and 0.840 for the heterogeneous model. In cross
      validation, the heterogeneous model produced a DSC higher than that produced by
      the homogeneous model in 23 of the 31 brain lesion ablations. Results of a
      paired, two-tailed Wilcoxon signed-rank test indicated that the performance
      improvement of the heterogeneous model over that of the homogeneous model was
      statistically significant (p < 0.01).

PMID- 29343141
TI  - Novel beta-lactam/beta-lactamase inhibitors versus alternative antibiotics for
      the treatment of complicated intra-abdominal infection and complicated urinary
      tract infection: a meta-analysis of randomized controlled trials.
AB  - INTRODUCTION: The aim of this study is to compare the efficacy and safety of
      novelBL/BLIs with alternative antibiotics for the treatment of cIAI and cUTI.
      Area covered: We performed a systematic review and meta-analysis of all
      randomized controlled trials comparing novel BL/BLIs with other antibiotics for
      the treatment of cIAI and cUTI. The primary outcome included clinical and
      microbiological treatment success. Expert commentary: We found that novel BL/BLIs
      obtained a similar clinical outcome with other antibiotics in CE population (OR =
      1.07, 95%CI = (0.80, 1.44), P = 0.64). However, novel BL/BLIs had better clinical
      treatment success in the cUTI subgroup (OR = 2.14, 95%CI = (1.06, 4.31), P =
      0.03). Furthermore, novel BL/BLIs achieved significant microbiological treatment
      success in patie nts with cUTI (OR = 1.70, 95%CI = (1.29, 2.25), P  =  0.0002)
      and had higher eradication rates for Gram-negative pathogens (OR = 1.82, 95%CI =
      (1.26, 2.64), P = 0.001) including E.coli and K.pneumoniae. No difference was
      observed concerning the incidence of mortality and adverse events between the two
      groups. Therefore, we concluded that novel BL/BLIs are not inferior to other
      available antibiotics for the treatment of cIAI, and they have advantages in
      patients with cUTI. Simultaneously, they are sensitive to Gram-negative
      pathogens, especially for E.coli and K.pneumoniae.

PMID- 29343142
TI  - A 500 U/2 mL dilution of abobotulinumtoxinA vs. placebo: randomized study in
      cervical dystonia.
AB  - : Purpose/aim: AbobotulinumtoxinA (Dysport(r), Ipsen Biopharmaceuticals, Inc.,
      Basking Ridge, NJ, USA) is an acetylcholine release inhibitor and a neuromuscular
      blocking agent. The United States prescribing information for abobotulinumtoxinA
      previously indicated only one dilution for cervical dystonia: 500 U/1 mL.
      Clinical trial data supporting a larger volume with a 500 U/2 mL dilution would
      offer clinicians flexibility with injection volume to better meet patient needs.
      MATERIALS AND METHODS: We conducted a 12-week, phase 3b, multicenter, randomized,
      double-blind, placebo-controlled trial (NCT01753310). Adult subjects with a
      primary diagnosis of cervical dystonia were randomized (2:1) to receive a single
      injection of either abobotulinumtoxinA, 500 U/2 mL dilution, or placebo. The
      primary efficacy endpoint was changed from baseline in Toronto Western Spasmodic
      Torticollis Rating Scale total score at Week 4. RESULTS: A total of 134 subjects
      (abobotulinumtoxinA, n = 89; placebo, n = 45) were randomized (intent-to-treat
      population) and 129 (abobotulinumtoxinA, n = 84; placebo, n = 45) completed the
      Week 4 primary endpoint evaluation (modified intent-to-treat population). In the
      modified intent-to-treat population, subjects receiving abobotulinumtoxinA
      experienced significantly greater changes from baseline versus placebo on the
      primary endpoint (weighted overall treatment difference -8.3, P < 0.001). The
      most common treatment-emergent adverse events (TEAEs) were dysphagia, muscle
      weakness, neck pain and headache. Overall, TEAEs were consistent with those
      reported in the abobotulinumtoxinA prescribing information (1 mL dilution) for
      cervical dystonia patients. CONCLUSIONS: This trial provides evidence that a 500
      U/2 mL dilution is an effective treatment for cervical dystonia and exhibits a
      safety profile consistent with the known safety profile of abobotulinumtoxinA.

PMID- 29343143
TI  - Colorectal cancer patients' preferences for type of caregiver during survivorship
      care.
AB  - PURPOSE: Colorectal cancer (CRC) survivors are currently included in a secondary
      care-led survivorship care programme. Efforts are underway to transfer this
      survivorship care to primary care, but met with some reluctance by patients and
      caregivers. This study assesses (1) what caregiver patients prefer to contact for
      symptoms during survivorship care, (2) what patient factors are associated with a
      preferred caregiver, and (3) whether the type of symptom is associated with a
      preferred caregiver. METHODS: A cross-sectional study of CRC survivors at
      different time points. For 14 different symptoms, patients reported if they would
      consult a caregiver, and who they would contact if so. Patient and disease
      characteristics were retrieved from hospital and general practice records.
      RESULTS: Two hundred and sixty patients participated (response rate 54%) of whom
      the average age was 67, 54% were male. The median time after surgery was seven
      months (range 0-60 months). Patients were divided fairly evenly between tumour
      stages 1-3, 33% had received chemotherapy. Men, patients older than 65 years, and
      patients with chronic comorbid conditions preferred to consult their general
      practitioner (GP). Women, patients with stage 3 disease, and patients that had
      received chemotherapy preferred to consult their secondary care provider. For all
      symptoms, patients were more likely to consult their GP, except for (1) rectal
      blood loss, (2) weight loss, and (3) fear that cancer had recurred, in which case
      they would consult both their primary and secondary care providers. Patients
      appreciated all caregivers involved in survivorship care highly; with 8 out of 10
      points. CONCLUSIONS: CRC survivors frequently consult their GP in the current
      situation, and for symptoms that could alarm them to a possible recurrent disease
      consult both their GP and secondary care provider. Patient and tumour
      characteristics influence patients' preferred caregiver.

PMID- 29343144
TI  - Cell-surface proteomics for the identification of novel therapeutic targets in
      cancer.
AB  - INTRODUCTION: Cancer is the second most common cause of death worldwide and its
      heterogeneity complicates therapy. Standard cytotoxic regiments disrupt rapidly
      dividing cells, regardless of their neoplastic status. The introduction of less
      toxic targeted therapies has partially contributed to the observed decrease in
      cancer-related mortality. Cell-surface proteins represent attractive targets for
      therapy, due to their easily-accessible localization and their involvement in
      essential signaling pathways, often dysregulated in cancer. Despite their
      clinical appeal, cell-surface proteins are often underrepresented in standard
      proteomic data sets, due to their poor solubility and lower expression levels
      compared to intracellular proteins. Areas covered: This review will summarize
      some of the available techniques for enriching the cell-surface proteome, and
      discuss their advantages, limitations and applicability to clinical sample
      testing. Moreover, we discuss currently available strategies for the development
      of novel targeted therapies in cancer. Expert commentary: The interest in
      elucidating the cancer-associated surfaceome is growing and will likely benefit
      from recent advancements in instrument sensitivity, method development, and a
      growing body of high-quality proteomics databases. Multiomics studies, in
      combination with functional validations (e.g. dropout screens), and evaluation of
      the healthy surfaceome, will likely aid in the selection of relevant targets for
      future therapy development.

PMID- 29343145
TI  - Principles of focused ultrasound.
AB  - Focused ultrasound (FUS/HIFU) relies on ablation of pathological tissues by
      delivering a sufficiently high level of acoustic energy in situ of the human
      body. Magnetic Resonance guided FUS (MRgFUS/HIFU) and Ultrasound guided
      (USgFUS/HIFU) are image guided techniques combined with therapeutic FUS for
      monitoring purposes. The principles and technologies of FUS/HiFU are described in
      this paper including the basics of MR guidance techniques and MR temperature
      mapping. Clinical applications of FUS/HIFU gained CE and FDA approvals for the
      treatment of various benign and few malignant lesions in the last two decades.
      Current technical limitations of ultrasound guided and MRI guided Focused
      Ultrasound, as well as adverse effects for the application of this technique are
      outlined including challenges of ablating moving organs (liver and kidney). An
      outlook to possible applications is provided; exampling clinical trials
      discussing future options.

PMID- 29343146
TI  - Induction of labor in cases of late preterm isolated oligohydramnios: is it
      justified?
AB  - OBJECTIVES: To analyze in a retrospective cohort study the outcomes of
      pregnancies with isolated oligohydramnios at the late preterm period (34-36.6
      weeks of gestation). STUDY DESIGN: This retrospective cohort study included three
      groups of women: (1) Women with isolated oligohydramnios whose pregnancy was
      managed conservatively (n = 33 births); (2) women with isolated oligohydramnios
      who were managed actively (i.e. induction of labor) (n = 111 births); and (3) a
      control group including women with normal amount of amniotic fluid who had a
      spontaneous late preterm delivery (n = 10,445 births). Maternal and fetal
      characteristics and obstetrics outcomes were collected from a computerized
      database of all deliveries at Soroka University Medical Center during the study
      period. RESULTS: Our cohort included 10,589 births. The rate of inducing labor
      was higher in the oligohydramnios groups compared to the controls (p < .001).
      There was an increase in the rate of cesarean section (CS) in the conservative
      treatment group (p < .001), compared with the other groups. Conservative
      management was associated with higher rates of maternal infection (p = .026),
      chorioamnionitis (p = .01), and transitory tachypnea of the newborn (p = .02).
      After controlling for confounding factors, mal presentation (OR = 19.9), and a
      prior CS (OR = 2.4) were independently associated with an increased risk for CS,
      while induction of labor was associated with a reduced risk for CS (OR = 0.28).
      CONCLUSIONS: Women with late preterm isolated oligohydramnios had a higher rate
      of induction of labor than women with a normal amount of amniotic fluid.
      Induction of labor seems to be beneficial to both the neonate and the mother as
      seen by a lower rate of CS conducted in this group, as well as lower maternal and
      neonatal morbidity in comparison to the conservative group. Therefore, women with
      oligohydramnios at late preterm may benefit from induction of labor.

PMID- 29343147
TI  - Estimation of intra-arterial chemotherapy distribution to the retina in pediatric
      retinoblastoma patients using quantitative digital subtraction angiography.
AB  - Background and purpose The purpose of this article is to estimate the
      distribution of superselective intra-arterial chemotherapy (IAC) delivery to
      ocular target tissue using quantitative digital subtraction angiography (qDSA).
      Materials and methods From March 2010 to January 2016, 50 ophthalmic artery
      contrast DSAs obtained immediately prior to IAC infusions in 22 patients were
      analyzed. This study was conducted under a retrospective review IRB (no. 10
      01862). Parametric color-coded DSAs (iFlow, Siemens Medical) were post-processed
      (MATLAB, The Mathworks Inc.) using two methods: two box regions of interest (pre
      retina and globe) and four custom regions of interest (ROIs-ophthalmic artery,
      choroid, supraclinoid internal carotid artery (ICA), cavernous ICA). Mean
      interobserver reliability of custom ROI selection is presented as a 95%
      confidence interval of interclass correlation, and fractional chemotherapy
      delivery to selected ROIs as means +/- standard deviation in this study. Results
      The estimated fraction of chemotherapy delivered to the globe with the first
      method was 79.5%. Percentage regional delivery using the second method was as
      follows: ophthalmic artery, 85.8%; choroid, 60.5%; supraclinoid ICA, 14.2%. The
      cavernous ICA ROI (encompassing distal catheter and potential reflux) gave a
      signal equivalent to 9.3% of total delivery. Conclusion Parametric color-coded
      qDSA can estimate the fraction of IAC delivered to the retina and other orbital
      structures in ocular retinoblastoma patients. This information can inform
      delivery location and dosing strategies on a patient-specific basis.

PMID- 29343149
TI  - Interventional bronchoscopy in adults.
AB  - INTRODUCTION: The field of interventional pulmonology (IP) is a rapidly maturing
      subspecialty of pulmonary medicine, which emphasizes advanced diagnostic and
      therapeutic bronchoscopy for the evaluation and management of central airway
      obstruction, mediastinal/hilar adenopathy and lung nodules/masses, as well as
      minimally invasive diagnostic and therapeutic pleural procedures. Areas covered:
      This review describes advances in diagnostic and therapeutic bronchoscopic
      techniques. Expert commentary: In the past decade, there has been a remarkable
      growth in available technology and equipment, as well as clinical and
      translational research efforts focused on patient-centered outcomes. Furthermore,
      the recent establishment of a uniform accreditation standard for all IP
      fellowship programs in the United States was an important step in the continued
      evolution of this subspecialty of pulmonary medicine.

PMID- 29343148
TI  - Predictors of intracranial hemorrhage volume and distribution in brain
      arteriovenous malformation.
AB  - Background and purpose Despite evidence regarding risk factors for brain
      arteriovenous malformation (bAVM)-associated spontaneous intracranial hemorrhage
      (ICH), few data exist describing the spectrum of clinical outcomes that bAVM
      associated ICH may manifest. This study aimed to identify the demographical,
      clinical, and bAVM anatomical variables associated with ICH volume and the
      presence of intraventricular hemorrhage (IVH) of ruptured bAVMs, two indicators
      of worse clinical outcome, to help better predict outcome for unruptured bAVMs.
      Methods Computed tomography images ( n = 169) of patients with ruptured bAVM in a
      prospectively maintained institutional database were retrospectively reviewed to
      calculate ICH volume and the presence or absence of IVH. Demographic, clinical,
      and bAVM characteristics information was summarized and analyzed with univariable
      and multivariable regression models to identify the associations of these
      features with ICH volume and the presence of IVH. Results Patient sex,
      exclusively deep venous drainage, and lobar location were associated with ICH
      volume in univariable analysis; exclusively deep venous drainage remained
      significant in multivariable analysis (PI = 0.33, 95% CI: 0.21-0.52, p < 0.001).
      Exclusively deep venous drainage, multiple feeding arteries, and venous stenosis
      were associated with IVH in univariable analysis; exclusively deep venous
      drainage (OR = 7.27, 95% CI: 1.94-27.29, p = 0.003) remained significant in
      multivariable analysis. Conclusions Variables associated with ICH volume and the
      presence of IVH in ruptured bAVMs were evaluated and identified. They impart
      information that may help predict the clinical outcome of unruptured bAVM, in
      turn aiding clinicians in treatment planning.

PMID- 29343150
TI  - Eight-year outcomes of a competency-based residency training program in
      orthopedic surgery.
AB  - BACKGROUND: The Division of Orthopaedic Surgery at the University of Toronto
      implemented a pilot residency training program that used a competency-based
      framework in July of 2009. The competency-based curriculum (CBC) deployed an
      innovative, modularized approach that dramatically intensified both the
      structured learning elements and the assessment processes. METHODS: This paper
      discusses the initial curriculum design of the CBC pilot program; the refinement
      of the curriculum using curriculum mapping that allowed for efficiencies in
      educational delivery; details of evaluating resident competence; feedback from
      external reviews by accrediting bodies; and trainee and program outcomes for the
      first eight years of the program's implementation. RESULTS: Feedback from the
      residents, the faculty, and the postgraduate residency training accreditation
      bodies on the CBC has been positive and suggests that the essential framework of
      the program may provide a valuable tool to other programs that are contemplating
      embarking on transition to competency-based education. CONCLUSIONS: While the
      goal of the program was not to shorten training per se, efficiencies gained
      through a modular, competency-based program have resulted in shortened time to
      completion of residency training for some learners.

PMID- 29343151
TI  - Correction to: Carpen et al., Presenting symptoms and clinical findings in HPV
      positive and HPV-negative oropharyngeal cancer patients.

PMID- 29343152
TI  - Impact of dosage timing on the bioavailability of oral anticancer medications: Is
      pre-prandial dosing equivalent to post-prandial dosing.
AB  - Many oral anticancer agents are recommended to be given either at least 1 h
      before or 2 h after a meal, according to the prescribing information. However,
      the effect of dosage timing of an oral anticancer agent with reference to food
      intake on anticancer treatment remains unclear. As shown by the literature survey
      and labeling analysis for oral anticancer drugs approved by the US Food and Drug
      Administration from 2010 to 2016, labeling information regarding dosage timing
      for several anticancer drugs appeared not be optimum, leading to suboptimal
      bioavailability and plasma drug concentrations. This supports a call to regularly
      recalibrate the labeling information for dosage timing of oral anticancer
      medications to minimize the risks of compromised efficacy or unintended
      toxicities.

PMID- 29343153
TI  - Cryptococcal infections in two patients receiving ibrutinib therapy for chronic
      lymphocytic leukemia.
AB  - Cryptococcal infections are responsible for significant morbidity and mortality
      in immunocompromised patients. Reports of these infections in patients on small
      molecular kinase inhibitors have not been widely reported in clinical trials. We
      describe one case of cryptococcal meningoencephalitis and one case of
      cryptococcal pneumonia in two patients who were receiving ibrutinib for chronic
      lymphocytic leukemia. Despite different sites of cryptococcal infection, both
      patients had similar presentations of acute illness. Patient 1 was worked up for
      health care-associated pneumonia, as well as acute sinusitis prior to the
      diagnosis of cryptococcal meningoencephalitis. He also had a more complex past
      medical history than patient 2. Patient 2 developed atrial fibrillation from
      ibrutinib prior to admission for presumed health care-associated pneumonia.
      Cryptococcal antigen testing was done sooner in this patient due to patient
      receiving high-dose steroids for the treatment of underlying hemolytic anemia. We
      conclude that patients who develop acute illness while receiving ibrutinib should
      be considered for cryptococcal antigen testing.

PMID- 29343154
TI  - Dasatinib-induced pulmonary arterial hypertension - A rare late complication.
AB  - Dasatinib is a dual Src/Abl tyrosine kinase inhibitor approved for frontline and
      second line treatment of chronic phase chronic myelogenous leukemia. Pulmonary
      arterial hypertension is defined by an increase in mean pulmonary arterial
      pressure >25 mmHg at rest. Dasatinib-induced pulmonary hypertension has been
      reported in less than 1% of patients on chronic dasatinib treatment for chronic
      myelogenous leukemia. The pulmonary arterial hypertension from dasatinib may be
      categorized as either group 1 (drug-induced) or group 5 based on various
      mechanisms that may be involved including the pathogenesis of the disease process
      of chronic myelogenous leukemia. There have been reports of dasatinib-induced
      pulmonary arterial hypertension being reversible. We report a case of pulmonary
      arterial hypertension in a 46-year-old female patient with chronic phase chronic
      myelogenous leukemia on dasatinib treatment for over 10 years. She had
      significant improvement in symptoms after discontinuation of dasatinib and
      initiation of vasodilators. Several clinical questions arise once patients
      experience significant adverse effects as discussed in our case.

PMID- 29343155
TI  - Carboxymethyl chitosan-zinc coating for prevention of pin tract infection: An
      animal model.
AB  - BACKGROUND: Pin tract infection is a common problem in orthopedic and
      traumatology surgery. The aim of this study was to investigate the efficacy of an
      implant coated with carboxymethyl chitosan-zinc (CMC-Zn2+) in prevention of pin
      tract infection. MATERIALS AND METHODS: Twenty-four male New Zealand White
      rabbits were randomized into two equal groups ( n = 12, uncoated and CMC-Zn2+).
      The implants were colonized with 1 * 106 colony forming units of Staphylococcus
      aureus and inserted into the lateral right proximal tibia in each rabbit. In each
      group, at 2 and 4 weeks post-surgery, five and seven rabbits were killed,
      respectively, to harvest the soft tissues around the implant as well as the hard
      tissue for histological analysis. The bone cross-sectional view, X-ray, and micro
      computed tomography (MUCT) were performed. RESULTS: The surgical sites in each
      animal were evaluated individually at both time points. No evident signs of
      infections were found in the CMC-Zn2+ group, while a high rate of infection was
      observed in the uncoated group where minor infections were 85.71% ( n = 12) and
      major infections 14.29% ( n = 12). The radiography, MUCT, and histological
      analysis showed no evident signs of infection in both groups at 2 weeks post
      surgery. However, at 4 weeks, signs of infection were found in all the animals in
      the uncoated group, whereas in the CMC-Zn2+ group, no infections were observed.
      The difference between the two groups was highly significant ( p = 0.00).
      CONCLUSIONS: Our study showed that CMC-Zn2+-coated implants were effective in
      preventing pin tract infection.

PMID- 29343156
TI  - Patient contributions during primary care consultations for hypertension after
      self-reporting via a mobile phone self-management support system.
AB  - OBJECTIVE: This paper reports on how the clinical consultation in primary care is
      performed under the new premises of patients' daily self-reporting and self
      generation of data. The aim was to explore and describe the structure, topic
      initiation and patients' contributions in follow-up consultations after eight
      weeks of self-reporting through a mobile phone-based hypertension self-management
      support system. DESIGN: A qualitative, explorative study design was used,
      examining 20 audio- (n = 10) and video-recorded (n = 10) follow-up consultations
      in primary care hypertension management, through interaction analysis. Clinical
      trials registry: ClinicalTrials.gov NCT01510301. SETTING: Four primary health
      care centers in Sweden. SUBJECTS: Patients with hypertension (n = 20) and their
      health care professional (n = 7). RESULTS: The consultations comprised three
      phases: opening, examination and closing. The most common topic was blood
      pressure (BP) put in relation to self-reported variables, for example, physical
      activity and stress. Topic initiation was distributed symmetrically between
      parties and BP talk was lifestyle-centered. The patients' contributed to the
      interpretation of BP values by connecting them to specific occasions, providing
      insights to the link between BP measurements and everyday life activities.
      CONCLUSION: Patients' contribution through interpretations of BP values to
      specific situations in their own lives brought on consultations where the patient
      as a person in context became salient. Further, the patients' and health care
      professionals' equal contribution during the consultations showed actively
      involved patients. The mobile phone-based self-management support system can thus
      be used to support patient involvement in consultations with a person-centered
      approach in primary care hypertension management Key points   The clinical
      consultation is important to provide opportunities for patients to gain
      understanding of factors affecting high blood pressure, and for health care
      professionals to motivate and promote changes in life-style. This study shows
      that self-reporting as base for follow-up consultations in primary care
      hypertension management can support patients and professionals to equal
      participation in clinical consultations. Self-reporting combined with increased
      patient-health care professional interaction during follow-up consultations can
      support patients in understanding the blood pressure value in relation to their
      daily life. These findings implicate that the interactive mobile phone self
      management support system has potential to support current transformations of
      patients as recipients of primary care, to being actively involved in their own
      health.

PMID- 29343157
TI  - The clinician-educator has no clothes.

PMID- 29343159
TI  - Celebrating 40 years of Medical Teacher: As the "last man standing" I look back
      to help us look forward.
AB  - INTRODUCTION: In this reflective, descriptive, analytical, first-person piece, I
      offer recollections, data, and literature to help elucidate the emergence of
      medical education as a scholarly field, as part of celebrating Medical Teacher's
      40-year anniversary. I emphasize the impressive growth of the professional
      literature in medical education, and recognize that much remains to be done.
      FINDINGS: Medical education as a domain for research and development has
      transitioned from being largely ignored during the first 20 of the past 60 years,
      through a slow growth phase, to rapid acceleration during the last 2 decades. By
      introducing the use and potential of "edumarkers," we can see that medical
      education as a focus of scholarly pursuits was absent to minimal before recent
      decades, and we can identify trends and questions that deserve further
      exploration. Concern and recommendations: Only a small subset of the large
      population assigned to instruct health professions learners actually conducts and
      responds to medical education scholarship. I raise several questions as possible
      guides to the future for those of us who are devoted to enhancing educational
      processes and outcomes for learners who are expected to help prevent and manage
      the health challenges faced by the world's people.

PMID- 29343158
TI  - Placebo Effects in Traumatic Brain Injury.
AB  - In recent years, several randomized controlled trials evaluating pharmaceutical
      treatments for traumatic brain injury (TBI) have failed to demonstrate efficacy
      over placebo, with both active and placebo arms improving at comparable rates.
      These findings could be viewed in opposing ways, suggesting on the one hand
      failure of the tested outcome, but on the other, representing evidence of robust
      placebo effects in TBI. In this article, we examine several of the primary
      psychological processes driving placebo effects (verbal suggestion, cognitive re
      framing, interpersonal interactions, conditioning, therapeutic alliance, anxiety
      reduction) as well as placebo neurobiology (top-down cortical regulation, reward
      system activation, dopaminergic and serotonergic neurotransmission). We then
      extrapolate from the literature to explore whether something inherent in TBI
      makes it particularly responsive to placebos. Viewed as such here, placebos may
      indeed represent a powerful and effective treatment for a variety of post-TBI
      complaints.

PMID- 29343160
TI  - Public School Nursing Practice in the United States.
AB  - School nursing practice has changed dramatically over the past 20 years, yet few
      nationally representative investigations describing the school nursing workforce
      have been conducted. The National School Nurse Workforce Study describes the
      demographic and school nursing practice patterns among self-reported public
      school nurses and the number and full-time equivalent (FTE) positions of all
      school nurses in the United States. Using a random sample stratified by
      public/private, region, school level, and urban/rural status from two large
      national data sets, we report on weighted survey responses of 1,062 public
      schools. Additional questions were administered to estimate the school nurse
      population and FTEs. Findings reported illustrate differences by strata in public
      school nurse demographics, practice patterns, and nursing activities and tasks.
      We estimate approximately 132,300 self-identified practicing public and private
      school nurses and 95,800 FTEs of school nurses in the United States. Research,
      policy, and school nursing practice implications are discussed.

PMID- 29343162
TI  - Psychopathy and Victim Selection: Does Nonverbal Decoding or Empathy Impact
      Vulnerability Ratings?
AB  - This research examined the role of psychopathic traits in perceptions of
      victimization and vulnerability. Community-member participants viewed video clips
      of victims, nonvictims, and victims who studied self-defense, then rated them on
      vulnerability and perceived history of victimization. Participants were most
      proficient at identifying nonvictims as nonvictims. Victims who studied self
      defense were harder to correctly identify than both victims and nonvictims and
      were rated by participants as less vulnerable and less likely to be victims than
      other victims and nonvictims. Moreover, individuals high in psychopathic traits,
      specifically Factor 2, were more likely than individuals low in psychopathic
      traits to correctly identify victims who practiced self-defense as victims, as
      well as nonvictims as victims. Unexpectedly, there was an observed negative
      relationship between facial affect decoding and identifying self-defense victims.
      The ability to correctly interpret facial expressions was found to partially
      mediate the relationship between psychopathy scores and the identification of
      self-defense victims. The results of this study provide insight into the ability
      of individuals with psychopathic traits to identify nonverbal cues associated
      with vulnerability. The results provide evidence that taking self-defense classes
      may be a meaningful intervention for victims, particularly.

PMID- 29343163
TI  - Magnetic resonance imaging changes following natalizumab discontinuation in
      multiple sclerosis patients with progressive multifocal leukoencephalopathy.
AB  - BACKGROUND: Detecting early progressive multifocal leukoencephalopathy-immune
      reconstitution inflammatory syndrome (PML-IRIS) is clinically relevant.
      OBJECTIVE: Evaluating magnetic resonance imaging (MRI) changes following
      natalizumab (NTZ) discontinuation and preceding PML-IRIS. METHODS: MRIs
      (including diffusion-weighted imaging (DWI), T2-weighted fluid-attenuated
      inversion recovery (T2-FLAIR), post-contrast T1-weighted sequences) were
      performed every week following PML diagnosis in 11 consecutive NTZ-PML patients.
      PML expansion, punctate lesions, contrast-enhancement, and mass-effect/edema were
      evaluated on each MRI sequence, following NTZ discontinuation. RESULTS: PML-IRIS
      occurred from 26 to 89 days after NTZ discontinuation. MRI changes prior to early
      PML-IRIS appeared significantly more pronounced using DWI compared to T2-FLAIR
      imaging ( p < 0.003). Two DWI features (marked PML expansion, punctate lesions)
      systematically preceded contrast-enhancement. CONCLUSION: Subtle changes may
      occur on DWI preceding contrast-enhancement.

PMID- 29343161
TI  - Addressing the Social Determinants of Health: A Call to Action for School Nurses.
AB  - Social determinants of health (SDOH), the conditions in which children are born,
      grow, live, work or attend school, and age, impact child health and contribute to
      health disparities. School nurses must consider these factors as part of their
      clinical practice because they significantly and directly influence child well
      being. We provide clinical guidance for addressing the SDOH when caring for
      children with three common health problems (obesity, insufficient sleep, and
      asthma). Given their unique role as school-based clinical experts, care
      coordinators, and student advocates, school nurses are well suited to serve as
      leaders in addressing SDOH.

PMID- 29343164
TI  - Inflammatory and Oxidative Responses in Pregnancies With Obesity and Periodontal
      Disease.
AB  - BACKGROUND: Maternal obesity is related to immunologic and inflammatory systemic
      modifications that may worsen the pregnancy inflammatory status. Hormonal changes
      during pregnancy can adversely affect oral biofilms and oral health initiating or
      worsening periodontal diseases, with enhanced local and systemic oxidative stress
      and inflammation. OBJECTIVE: The aim of this study was to examine the
      relationship between local salivary and systemic parameters of oxidative stress
      and inflammation in relation to obesity and periodontal diseases. STUDY DESIGN:
      Sixty-two women with singleton pregnancies were enrolled. Twenty-seven women were
      normal weight (NW; 18.5< body mass index [BMI] <25 kg/m2) and 35 obese (BMI >=30
      kg/m2). Seventeen of the obese had gestational diabetes mellitus (GDM). During
      third trimester, periodontal status was evaluated, saliva (s) was collected to
      assess total antioxidant capacity (s-TAC) and C-reactive protein (s-CRP) levels,
      and venous plasma (p) was used to measure CRP levels (p-CRP). Maternal, fetal,
      and placental data were registered at delivery. RESULTS: Levels of s-TAC, s-CRP,
      and p-CRP were significantly higher in obese, particularly in the presence of
      GDM, compared to NW and related to each other ( P = .000; r > 0.59), to maternal
      BMI ( P = .000; r > 0.52), and fasting glycemia ( P < .002; r > 0.47).
      Periodontal disease was more frequent in obese groups (80%) versus NW (52%; P =
      .04), particularly when GDM was diagnosed ( P = .009). A significant interaction
      effect between maternal BMI and oral condition was found for s-TAC levels. Obese
      with periodontitis showed significant increase in local and systemic parameters
      versus NW. CONCLUSION: Obesity and periodontal disease could synergistically
      amplify the inflammatory and oxidative status, resulting in increased local and
      systemic biomarkers particularly when GDM is diagnosed.

PMID- 29343165
TI  - HIV and renal disease: a contemporary review.
AB  - The presence of human immunodeficiency virus (HIV)-related kidney disease is an
      important cause of mortality and morbidity. HIV infection induces renal injury by
      direct cytotoxicity or immune complex-mediated glomerulonephritis in patients
      with genetic susceptibility factors. In the last decades, with the development
      and diffusion of combination antiretroviral therapy, which has prolonged patient
      survival, there has been a shift in the spectrum of renal diseases in HIV
      infected patients, with the decrease of glomerular diseases and increase in the
      role of nephrotoxicity and co-morbidities. This review provides a contemporary
      and critical review on the main renal syndromes occurring in HIV-infected
      patients.

PMID- 29343166
TI  - Consensus statement of the International Summit on Intellectual Disability and
      Dementia on valuing the perspectives of persons with intellectual disability.
AB  - The International Summit on Intellectual Disability and Dementia covered a range
      of issues related to dementia and intellectual disability, including the dearth
      of personal reflections of persons with intellectual disability affected by
      dementia. This article reflects on this deficiency and explores some of the
      personal perspectives gleaned from the literature, from the Summit attendees and
      from the experiences of persons with intellectual disability recorded or scribed
      in advance of the two-day Summit meeting. Systemic recommendations included
      reinforcing the value of the involvement of persons with intellectual disability
      in (a) research alongside removing barriers to inclusion posed by
      institutional/ethics review boards, (b) planning groups that establish supports
      for dementia and (c) peer support. Practice recommendations included (a) valuing
      personal perspectives in decision-making, (b) enabling peer-to-peer support
      models,

PMID- 29343167
TI  - A cluster randomised feasibility trial of clinically assisted hydration in cancer
      patients in the last days of life.
AB  - BACKGROUND: The provision of clinically assisted hydration at the end-of-life is
      one of the most contentious issues in medicine. AIM: The aim of this feasibility
      study was to answer the question 'can a definitive (adequately powered) study be
      done?' DESIGN: The study was a cluster randomised trial, with sites randomised on
      a one-to-one basis to intervention 'A' (regular mouth care and usual other care)
      or intervention 'B' (clinically assisted hydration, mouth care and usual other
      care). Participants were assessed every 4 h, and data collected on clinical
      problems, therapeutic interventions and overall survival. SETTING/PARTICIPANTS:
      The study was conducted at 12 sites/'clusters' with specialist palliative care
      teams (4 cancer centres and 8 hospices), and participants were cancer patients in
      the last week of life who were unable to maintain sufficient oral fluid intake.
      RESULTS: The study achieved its pre-determined criteria for success. Two hundred
      patients were recruited to the study, and 199 participants completed the study,
      over a 1-year period. A total of 38.5% participants discontinued clinically
      assisted hydration due to adverse effects: none of these adverse events were
      rated as 'severe' or worse in intensity. The primary reasons for discontinuation
      were site problems ( n = 2), localised oedema ( n = 13), generalised oedema ( n =
      5), respiratory secretions ( n = 6) and nausea and vomiting ( n = 1). CONCLUSION:
      The results of this feasibility study suggest that a definitive study can be
      done, but that minor changes are needed to the protocol to standardise the
      administration of clinically assisted hydration (which may reduce the incidence
      of certain adverse effects).

PMID- 29343168
TI  - Assessment of goals and priorities in patients with a chronic condition: a
      secondary quantitative analysis of determinants across 11 countries.
AB  - OBJECTIVE: To assess the impact of patient characteristics, patient-professional
      engagement, communication and context on the probability that healthcare
      professionals will discuss goals or priorities with older patients. DESIGN:
      Secondary analysis of cross-sectional data from the 2014 Commonwealth Fund
      International Health Policy Survey of Older Adults. SETTING: 11 western
      countries. SUBJECTS: Community-dwelling adults, aged 55 or older. MAIN OUTCOME
      MEASURE: Assessment of goals and priorities. RESULTS: The final sample size
      consisted of 17,222 respondents, 54% of whom reported an assessment of their
      goals and priorities (AGP) by healthcare professionals. In logistic regression
      model 1, which was used to analyse the entire population, the determinants found
      to have moderate to large effects on the likelihood of AGP were information
      exchange on stress, diet or exercise, or both. Country (living in Sweden) and
      continuity of care (no regular professional or organisation) had moderate to
      large negative effects on the likelihood of AGP. In model 2, which focussed on
      respondents who experienced continuity of care, country and information exchange
      on stress and lifestyle were the main determinants of AGP, with comparable odds
      ratios to model 1. Furthermore, a professional asking questions also increased
      the likelihood of AGP. CONCLUSIONS: Continuity of care and information exchange
      is associated with a higher probability of AGP, while people living in Sweden are
      less likely to experience these assessments. Further study is required to
      determine whether increasing information exchange and professionals asking more
      questions may improve goal setting with older patients. Key points   A patient
      goal-oriented approach can be beneficial for older patients with chronic
      conditions or multimorbidity; however, discussing goals with these patients is
      not a common practice. The likelihood of discussing goals varies by country,
      occurring most commonly in the USA, and least often in Sweden. Country-level
      differences in continuity of care and questions asked by a regularly visited
      professional affect the goal discussion probability. Patient characteristics,
      including age, have less impact than expected on the likelihood of sharing goals.

PMID- 29343169
TI  - Patients' and carers' perspectives of palliative care in general practice: A
      systematic review with narrative synthesis.
AB  - BACKGROUND: General practitioners have overall responsibility for community care,
      including towards end of life. Current policy places generalists at the centre of
      palliative care provision. However, little is known about how patients and carers
      understand the general practitioner's role. AIMS: To explore patient and carer
      perspectives of (1) the role of the general practitioner in providing palliative
      care to adult patients and (2) the facilitators and barriers to the general
      practitioner's capacity to fulfil this perceived role. DESIGN: Systematic
      literature review and narrative synthesis. DATA SOURCES: Seven electronic
      databases (MEDLINE, Embase, PsycINFO, BNI, CINAHL, Cochrane and HMIC) were
      searched from inception to May 2017. Two reviewers independently screened papers
      at title, abstract and full-text stages. Grey literature, guideline, hand
      searches of five journals and reference list/citation searches of included papers
      were undertaken. Data were extracted, tabulated and synthesised using narrative,
      thematic analysis. RESULTS: A total of 25 studies were included: 14 employed
      qualitative methods, 8 quantitative survey methods and 3 mixed-methods. Five key
      themes were identified: continuity of care, communication between primary and
      secondary care, contact and accessibility, communication between general
      practitioner and patient, and knowledge and competence. CONCLUSION: Although the
      terminology and context of general practice vary internationally, themes relating
      to the perceived role of general practitioners were consistent. General
      practitioners are considered well placed to provide palliative care due to their
      breadth of clinical responsibility, ongoing relationships with patients and
      families, and duty to visit patients at home and coordinate healthcare resources.
      These factors, valued by service users, should influence future practice and
      policy development.

PMID- 29343170
TI  - Accuracy of Ultrasonographic Measurements of Inferior Vena Cava to Determine
      Fluid Responsiveness: A Systematic Review and Meta-Analysis.
AB  - OBJECTIVE: Fluid responsiveness is the ability to increase the cardiac output in
      response to a fluid challenge. Only about 50% of patients receiving fluid
      resuscitation for acute circulatory failure increase their stroke volume, but the
      other 50% may worsen their outcome. Therefore, predicting fluid responsiveness is
      needed. In this purpose, in recent years, the assessment of the inferior vena
      cava (IVC) through ultrasound (US) has become very popular. The aim of our work
      was to systematically review all the previously published studies assessing the
      accuracy of the diameter of IVC or its respiratory variations measured through US
      in predicting fluid responsiveness. DATA SOURCES: We searched in the MEDLINE
      (PubMed), Embase, Web of Science databases for all relevant articles from
      inception to September 2017. STUDY SELECTION: Included articles specifically
      addressed the accuracy of IVC diameter or its respiratory variations assessed by
      US in predicting the fluid responsiveness in critically ill ventilated or not,
      adult or pediatric patients. DATA EXTRACTION: We included 26 studies that
      investigated the role of the caval index (IVC collapsibility or distensibility)
      and 5 studies on IVC diameter. DATA SYNTHESIS: We conducted a meta-analysis for
      caval index with 20 studies: The pooled area under the curve, logarithmic
      diagnostic odds ratio, sensitivity, and specificity were 0.71 (95% confidence
      interval [CI]: 0.46-0.83), 2.02 (95% CI: 1.29-2.89), 0.71 (95% CI: 0.62-0.80),
      and 0.75 (95% CI: 0.64-0.85), respectively. CONCLUSION: An extreme heterogeneity
      of included studies was highlighted. Ultrasound evaluation of the diameter of the
      IVC and its respiratory variations does not seem to be a reliable method to
      predict fluid responsiveness.

PMID- 29343171
TI  - Prognosis of Acute Respiratory Distress Syndrome in Patients With Hematological
      Malignancies.
AB  - INTRODUCTION: The intensive care unit (ICU) admission of patients with
      hematologic malignancies is gradually increasing. Life-threatening events are
      common, and acute respiratory distress syndrome (ARDS) is one of the most
      critical conditions. The aim of this study was to investigate the clinical
      characteristics and outcomes of ARDS in patients with hematological malignancies
      admitted to the ICU. METHODS: A retrospective study was performed on all patients
      with ARDS with hematological malignancies in a single tertiary teaching hospital
      between 2008 and 2015. Data on the treatment of and the outcomes of ARDS were
      collected to determine the clinical characteristics associated with ICU
      mortality. RESULTS: During the 8-year study period, among a total of 821 patients
      with ARDS admitted to the ICU, all 185 patients with hematological malignancies
      were included in the analysis. Most of the patients (88.1%) had moderate-to
      severe ARDS, and the median PaO2/FiO2 ratio was 122 (interquartile range: 88
      157). The overall ICU mortality rate was 57.3% (50.0% for mild, 52.0% for
      moderate, and 67.7% for severe ARDS). After the univariate and the multivariate
      logistic regressions, the factors independently associated with a higher ICU
      mortality were severe ARDS (odds ratio [OR]: 2.47; 95% confidence interval [CI]:
      1.17-5.25), identification of carbapenem-resistant gram-negative bacteria (OR:
      6.61; 95% CI: 1.31-33.41), the amount of blood product transfusion (OR: 1.25; 95%
      CI: 1.13-1.38), and the progressive or refractory disease (OR: 3.01; 95% CI: 1.31
      6.91). Mortality was independently lower in patients who received the initial low
      tidal volume ventilation (OR: 0.37, 95% CI: 0.14-0.96). CONCLUSION: The outcome
      of ARDS in patients with hematological malignancies is associated with the
      severity of the underlying diseases, the presence of multidrug-resistance
      pathogens, and the amount of transfusion; however, strict application of low
      tidal volume ventilation may improve the outcome of these patients at the time of
      diagnosis.

PMID- 29343172
TI  - Quantification of brake data acquired with a brake power meter during simulated
      cross-country mountain bike racing.
AB  - There is currently a dearth of information describing cycling performance outside
      of propulsive and physiological variables. The aim of the present study was to
      utilise a brake power meter to quantify braking during a multi-lap cross-country
      mountain bike time trial and to determine how braking affects performance. A
      significant negative association was determined between lap time and brake power
      (800.8 +/- 216.4 W, mean +/- SD; r = -0.446; p < 0.05), while the time spent
      braking (28.0 +/- 6.4 s) was positively associated with lap time (314.3 +/- 37.9
      s; r = 0.477; p < 0.05). Despite propulsive power decreasing after the first lap
      (p < 0.05), lap time remained unchanged (p > 0.05) which was attributed to
      decreased brake work (p < 0.05) and brake time (p < 0.05) in both the front and
      rear brakes by the final lap. A multiple regression model incorporating braking
      and propulsion was able to explain more of the variance in lap time (r2 = 0.935)
      than propulsion alone (r2 = 0.826). The present study highlights that riders'
      braking contributes to mountain bike performance. As riders repeat a cross
      country mountain bike track, they are able to change braking, which in turn can
      counterbalance a reduction in power output. Further research is required to
      understand braking better.

PMID- 29343173
TI  - Effects of two feedback interventions on end-of-life outcomes in nursing home
      residents with dementia: A cluster-randomized controlled three-armed trial.
AB  - BACKGROUND: Despite increased attention for palliative care in dementia, recent
      studies found burdensome symptoms and unmet family caregiver needs in the last
      phase of life. Feedback is being used to improve the quality of palliative care,
      but we do not know how effective it is. AIM: To assess the effect of two feedback
      strategies on perceived quality of end-of-life care and comfort in dying nursing
      home residents with dementia. METHODS: In a cluster-randomized controlled trial,
      the End-of-Life in Dementia-Satisfaction With Care and the End-of-Life in
      Dementia-Comfort Assessment in Dying scales were completed by bereaved family
      caregivers of residents with dementia of 18 Dutch nursing homes. Two feedback
      strategies, generic feedback with mean End-of-Life in Dementia-scores and
      feedback with individual (patient-specific) End-of-Life in Dementia-scores, were
      compared to no feedback provided. The intervention groups discussed End-of-Life
      in Dementia-ratings in team meetings and formulated actions to improve care.
      Multi-level analyses assessed effects. RESULTS: A total of 668 families rated the
      End-of-Life in Dementia-instruments. Compared to no feedback, the generic
      strategy resulted in lower quality of end-of-life care in unadjusted ( B = -1.65,
      confidence interval = -3.27; -0.21) and adjusted analyses ( B = -2.41, confidence
      interval = -4.07; -0.76), while there was no effect on comfort. The patient
      specific strategy did not affect the quality of end-of-life care, but it
      increased comfort in unadjusted analyses (only, B = 2.20, confidence interval =
      0.15; 4.39; adjusted: B = 1.88, confidence interval = -0.34; 4.10). CONCLUSION:
      Neither feedback strategy improved end-of-life outcome. Perhaps, skills to
      translate the feedback into care improvement actions were insufficient. Feedback
      with favorable family ratings might even have triggered opposite effects. Trial
      number: NTR3942.

PMID- 29343174
TI  - Small Molecules for Neural Stem Cell Induction.
AB  - Generation of induced pluripotent stem cells (iPSCs) from other somatic cells has
      provided great hopes for transplantation therapies. However, these cells still
      cannot be used for clinical application due to the low reprogramming and
      differentiation efficiency beside the risk of mutagenesis and tumor formation.
      Compared to iPSCs, induced neural stem cells (iNSCs) are easier to terminally
      differentiate into neural cells and safe; thus, iNSCs hold more opportunities
      than iPSCs to treat neural diseases. On the other hand, recent studies have
      showed that small molecules (SMs) can dramatically improve the efficiency of
      reprogramming and SMs alone can even convert one kind of somatic cells into
      another, which is much safer and more effective than transcription factor-based
      methods. In this study, we provide a review of SMs that are generally used in
      recent neural stem cell induction studies, and discuss the main mechanisms and
      pathways of each SM.

PMID- 29343175
TI  - Activity-Based Goals Generated by Older Adults With Mild Cognitive Impairment.
AB  - Client-centered care is one promising rehabilitation model that may support the
      unique needs of older adults with mild cognitive impairment (MCI). This secondary
      analysis examined (a) whether older adults with MCI generated activity-based
      goals using a client-centered model and (b) the types of goals generated.
      Thirteen older adults with MCI addressed 55 goals. Using client-centered care,
      the participants generated goals despite subtle limitations in activities and
      participation. Participants generated the greatest number of goals related to
      instrumental activities of daily living. This study demonstrated that older
      adults with MCI generated goals through a client-centered model. This is
      important because older adults with MCI are at risk for disability, and they may
      benefit from early rehabilitation care models that minimize activity limitations
      and participation restrictions despite underlying cognitive impairments.

PMID- 29343177
TI  - Wide QRS alternans caused by propafenone toxicity.

PMID- 29343176
TI  - On understanding the nature of interpersonal conflict between coaches and
      athletes.
AB  - Conflict is a part of coach-athlete relationships and should be carefully
      considered as it can have effects on the quality of coaching and the level of
      performance. Despite its practical relevance, there is a dearth of research
      around coach-athlete conflict. Therefore, the current study aimed to explore the
      characteristics and topics of conflict, as well as coaches and athletes'
      emotional, cognitive and behavioural experiences during conflict. A total of 22
      independent coaches and athletes participated in semi-structured interviews
      evolving around the nature of interpersonal conflict. After all interviews were
      transcribed, a deductive-inductive content analysis was conducted. This was
      guided by the interview schedule as well as the by the conceptual framework of
      conflict in sport relationships (Wachsmuth, Jowett, & Harwood, 2017). Data were
      divided into five main categories: Conflict characteristics and conflict topics,
      as well as conflict cognitions, emotions, and behaviours. Findings highlighted
      the variety of ways in which participants understood and interpreted
      interpersonal conflict and how their impressions of conflict influenced its
      evolving process. Considering the participants' cognitive, emotional and
      behavioural expressions of conflict, it became apparent that conflict can be
      described through uncertain, escalating and problem-orientated responses.
      Practical applications concerning (mal-) adaptive responses to conflict are
      discussed. (199/200).

PMID- 29343178
TI  - Impact of clinical pharmacists on atherosclerotic risk factor management in an
      integrated heart and vascular clinic.

PMID- 29343179
TI  - B-type natriuretic peptide for prediction of incident clinically significant
      abdominal aortic aneurysm: A population-based prospective study.
AB  - Pathogenesis of abdominal aortic aneurysm (AAA) is unclear. The aim of this study
      was to evaluate inflammatory and hemodynamic plasma biomarkers as predictors for
      AAA in the prospective longitudinal cohort of middle-aged individuals from the
      cardiovascular cohort of the Malmo Diet and Cancer Study ( n=5551; 1991-94). C
      reactive protein, cystatin C, copeptin, N-terminal pro-B-type natriuretic peptide
      (N-BNP), midregional pro-atrial natriuretic peptide (MR-proANP) and conventional
      risk factors at baseline were measured in patients with incident AAA during
      follow-up and compared to individuals without a diagnosis of AAA. Subjects were
      followed until 31 December 2013. Multivariable analyses were expressed in terms
      of hazard ratios (HR) per 1 standard deviation increment of each respective log
      transformed plasma biomarker in the Cox proportional hazard models. Mean follow
      up time was 20.7 years. Cumulative incidence of AAA was 1.5% (men 2.9%, women
      0.5%). Mean age of individuals with incident AAA was 59.7 years at study entry
      and AAA was diagnosed on average 14 years later. Adjusting for age, sex, smoking,
      body mass index, hypertension and diabetes mellitus, N-BNP (HR 1.29; 95% CI 1.03
      1.62), but not MR-proANP (HR 1.20; 95% CI 0.95-1.50), was independently
      associated with incident AAA. In conclusion, the plasma biomarker N-BNP was
      associated with future development of AAA, which implies that this marker is a
      sensitive indicator of early subclinical cardiovascular disease.

PMID- 29343180
TI  - Images in Vascular Medicine: Standing waves are not distinctive to conventional
      angiograms.

PMID- 29343181
TI  - Experiencing abortion rights in India through issues of autonomy and legality: A
      few controversies.
AB  - Abortion laws in India, like other laws, are premised on the 1861 British Penal
      Code. The Medical Termination of Pregnancy Act was passed in 1971 to circumvent
      the criminality clause around abortion. Yet the law continues to render invisible
      women's right to choose. Legal procedures have often hindered in permitting
      abortion, resulting in the death of a mother or the foetus. Despite the latest
      techno-medical advances, the laws have remained stagnant or rather restrictive,
      complicated further by selective female foetus abortions. Legal resistance to
      abortion-seeking after 20 weeks gestation adversely affects women, depriving them
      of autonomy of choice. In this paper, raising important gender, health and
      ethical issues are illustrated through a recent legal case in India. Feminist
      campaigns against the legal mindset in India are emerging.

PMID- 29343182
TI  - Fibronectin Enhances Cartilage Repair by Activating Progenitor Cells Through
      Integrin alpha5beta1 Receptor.
AB  - This study aimed to determine the effect of fibronectin (FN) on cartilage
      regeneration through the activation of chondrogenic progenitor cells (CPCs).
      Cells were isolated from the knee cartilage of mice and cultured in the presence
      of various concentrations of FN. Proliferation, migration, and chondrogenic
      differentiation assays were performed in vitro. In some experiments, CPCs were
      preincubated with anti-integrin alpha5beta1 antibody for 60 min before FN
      treatment to block the integrin alpha5beta1 receptor. Soluble FN was mixed with
      Pluronic F-127 and injected into the joint cavity in an early-stage
      osteoarthritis model. Cartilage repair was evaluated histologically,
      biochemically, and biomechanically. In vitro, we observed that the isolated CPCs,
      which exhibited stem cell-relevant markers, proliferated most at a concentration
      of 20 MUg/mL FN (p < 0.05). In addition, FN enhanced the proliferation,
      migration, and chondrogenic differentiation capacity of CPCs, and the enhancement
      was significantly decreased by blockade of the integrin alpha5beta1 receptor (p <
      0.05). In vivo, FN also significantly promoted cartilage repair along with
      increased CPC activation and integrin alpha5beta1 expression (p < 0.05). These
      findings suggest that FN enhances CPC proliferation, migration, and chondrogenic
      differentiation through the integrin alpha5beta1-dependent signaling pathway.
      Based on these results, a novel and promising therapy focused on targeted
      activation of CPCs by FN could be developed for the treatment of cartilage
      injuries in a clinical setting.

PMID- 29343183
TI  - The acute angiogenic signalling response to low-load resistance exercise with
      blood flow restriction.
AB  - This study investigated protein kinase activation and gene expression of
      angiogenic factors in response to low-load resistance exercise with or without
      blood flow restriction (BFR). In a repeated measures cross-over design, six males
      performed four sets of bilateral knee extension exercise at 20% 1RM (reps per set
      = 30:15:15:continued to fatigue) with BFR (110 mmHg) and without (CON). Muscle
      biopsies were obtained from the vastus lateralis before, 2 and 4 h post-exercise.
      mRNA expression was determined using real-time RT-PCR. Protein
      phosphorylation/expression was determined using Western blot. p38MAPK
      phosphorylation was greater (p = 0.05) at 2 h following BFR (1.3 +/- 0.8)
      compared to CON (0.4 +/- 0.3). AMPK phosphorylation remained unchanged. PGC
      1alpha mRNA expression increased at 2 h (5.9 +/- 1.3 vs. 2.1 +/- 0.8; p = 0.03)
      and 4 h (3.2 +/- 0.8 vs. 1.5 +/- 0.4; p = 0.03) following BFR exercise with no
      change in CON. PGC-1alpha protein expression did not change following either
      exercise. BFR exercise enhanced mRNA expression of vascular endothelial growth
      factor (VEGF) at 2 h (5.2 +/- 2.8 vs 1.7 +/- 1.1; p = .02) and 4 h (6.8 +/- 4.9
      vs. 2.5 +/- 2.7; p = .01) compared to CON. mRNA expression of VEGF-R2 and hypoxia
      inducible factor 1alpha increased following BFR exercise but only eNOS were
      enhanced relative to CON. Matrix metalloproteinase-9 mRNA expression was not
      altered in response to either exercise. Acute low-load resistance exercise with
      BFR provides a targeted angiogenic response potentially mediated through enhanced
      ischaemic and shear stress stimuli.

PMID- 29343184
TI  - Foot strike pattern in preschool children during running: sex and shod-unshod
      differences.
AB  - PURPOSE: This study aims to determine the foot strike patterns (FSPs) and neutral
      support (no inversion [INV]/eversion [EVE] and no foot rotation) in preschool
      children, as well as to determine the influence of shod/unshod conditions and
      sex. METHODS: A total of 1356 children aged 3-6 years (673 boys and 683 girls)
      participated in this study. A sagittal and frontal-plane video (240 Hz) was
      recorded using a high-speed camcorder to record the following variables: rearfoot
      strike (RFS), midfoot strike (MFS), forefoot strike (FFS), inversion/ eversion
      (INV/EVE) and foot rotation on initial contact. RESULTS: There were no between
      sex significant differences in both shod and unshod conditions in RFS. In the
      unshod condition, there was a significant reduction (p < 0.001) of RFS prevalence
      in both boys (shod condition = 44.2% vs. 34.7% unshod condition) and girls (shod
      condition = 48.5% vs. 36.1% unshod condition). As for neutral support, there were
      no between-sex differences in both shod and unshod conditions or in the shod
      unshod comparison. CONCLUSION: In preschool children, no between-sex differences
      were found in relation to prevalence of RFS and neutral support (no INV/EVE).
      Shod running alters FSP of running barefoot, producing a significant increase of
      RFS prevalence.

PMID- 29343185
TI  - Exploring protein-protein intermolecular recognition between meprin-alpha and
      endogenous protease regulator cystatinC coupled with pharmacophore elucidation.
AB  - Meprins are a group of zinc metalloproteases of the astacin family which play a
      pivotal role in several physiological and pathologocal diseases. The inhibition
      of the meprins by various inhibitors, macromolecular and small molecules, is
      crucial in the control of several diseases. Human cystatinC, an amyloidogenic
      protein, is reported to be an endogenous inhibitor of meprin-alpha. In this
      computational study, we elucidate a rational model for meprinalpha-cystatinC
      complex using protein-protein docking. The complex model as well as the unbound
      form was evaluated by molecular dynamics simulation. A simulation study revealed
      higher stability of the complex owing to the presence of several interactions.
      Virtual alanine mutagenesis helps in identifying the hotspots on both proteins.
      Based on the frequency of occurrence of hotspot amino acids, it was possible to
      enumerate the important amino acids primarily responsible for protein stability
      present at the amino-terminal end of cystatin. Finally, pharmacophore elucidation
      carried out based on the information obtained from a series of small molecular
      inhibitors against meprin-alpha can be utilized in future for rational drug
      design and therapy.

PMID- 29343186
TI  - Association between palliative care and life-sustaining treatments for patients
      with dementia: A nationwide 5-year cohort study.
AB  - BACKGROUND: The association between palliative care and life-sustaining
      treatments for patients with dementia is unclear in Asian countries. AIM: To
      analyse the use of palliative care and its association with aggressive treatments
      based on Taiwanese national data. DESIGN: A matched cohort study was conducted.
      The association between intervention and outcome was evaluated using conditional
      logistic regression analyses. SETTING/PARTICIPANTS: The source population
      comprised 239,633 patients with dementia diagnosed between 2002 and 2013. We
      selected patients who received palliative care between 2009 and 2013 (the
      treatment cohort; N = 1996) and assembled a comparative cohort ( N = 3992)
      through 1:2 matching for confounding factors. RESULTS: After 2009, palliative
      care was provided to 3928 (1.64%) patients of the dementia population. The odds
      ratio for undergoing life-sustaining treatments in the treatment cohort versus
      the comparative cohort was <1 for most treatments (e.g. 0.41 for mechanical
      ventilation (95% confidence interval: 0.35-0.48)). The odds ratio was >1 for some
      treatments (e.g. 1.73 for tube feeding (95% confidence interval: 1.54-1.95)).
      Palliative care was more consistently associated with fewer life-sustaining
      treatments for those with cancer. CONCLUSIONS: Palliative care is related to
      reduced life-sustaining treatments for patients with dementia. However, except in
      the case of tube feeding, which tended to be provided alongside palliative care
      regardless of cancer status, having cancer possibly had itself a protective
      effect against the use of life-sustaining treatments. Modifying the eligibility
      criteria for palliative care in dementia, improving awareness on the terminal
      nature of dementia and facilitating advance planning for dementia patients may be
      priorities for health policies.

PMID- 29343187
TI  - Mechanical and antibacterial properties of benzothiazole-based dental resin
      materials.
AB  - A synthesized benzothiazole containing mono-methacrylate monomer BTTMA was
      incorporated into Bis-GMA/TEGDMA dental resin system with a series of mass
      concentration from 5 to 30 wt.% as an antibacterial agent. The influence of BTTMA
      on physicochemical properties of dental resin system, such as double bond
      conversion (DC), volumetric shrinkage (VS), flexural strength (FS) and modulus
      (FM), water sorption (WS) and solubility (SL) were investigated. Direct contact
      testing and agar diffusion testing were used to evaluate the antibacterial
      activity of BTTMA containing dental resin. The results showed that BTTMA could
      endow dental resin with significant antibacterial activity when its concentration
      reached a certain amount (20 wt.%), and the antibacterial activity of BTTMA
      containing dental resin was mainly attributed to the immobilized BTTMA instead of
      the unreacted leachable BTTMA. BTTMA had no negative effect on physicochemical
      properties of dental resin, and even some BTTMA containing dental resins had
      advantages like higher DC, lower VS and WS when compared with control resin.
      Therefore, BTTMA could be considered as a suitable antibacterial agent in dental
      material, but much more researches concerned about biocompatibility should be
      done in future to prove whether it could be applied in clinic.

PMID- 29343188
TI  - Technique selection in young female gymnasts: Elbow and wrist joint loading
      during the cartwheel and round-off.
AB  - Biophysical loading of the elbow and wrist is a potential reason for chronic
      lesions in gymnastics and present a real concern for coaches, scientist and
      clinicians. Previous research has identified injury risk factors during round-off
      (RO) skills in elite female gymnasts. The aim of this study was to investigate
      key elbow and wrist joint injury risk factors during different techniques of
      fundamental cartwheel (CW) and RO skills performed by young female artistic
      gymnasts. Seventeen active young female gymnasts performed 30 successful trials
      of both CW and RO from a hurdle step with three different hand positions
      (parallel (10), T-shape (10) and reverse (10)). Synchronised kinematic (240 Hz)
      and kinetic (1200 Hz) data were collected for each trial. One-way repeated
      measures ANOVA and effect size (ES) were used for statistical analysis. The
      results showed statistically significant differences (P < .05) and large ES
      (>0.8) among hand positions for peak vertical ground reaction force (VGRF), peak
      elbow compression force, peak wrist compression force, elbow internal adduction
      moment and wrist dorsiflexion angle. In conclusion, the parallel and reverse
      techniques increase peak VGRF, elbow and wrist compression forces, and elbow
      internal adduction moment. These differences indicate that the parallel and
      reverse techniques may increase the potential of elbow and wrist injuries in
      young gymnasts compared with the T-shape technique; this is of particular
      importance with the high frequency of the performance of these fundamental
      skills.

PMID- 29343189
TI  - Translating Ancient Alchemy: Fragments of Graeco-Egyptian Alchemy in Arabic
      Compendia.
AB  - Translation played a vital role in the development and transfer of alchemy in
      Antiquity and the Early Middle Ages. Since its origins in Graeco-Roman Egypt,
      alchemy was encapsulated in Greek texts which allegedly relied on Persian or
      Egyptian sources. Later, a variety of Greek and Byzantine writings were
      translated into Syriac and Arabic, and these translations were in turn fragmented
      and disseminated in later Arabic compendia. This paper will first review the main
      phases of this historical process of transmission of alchemy from one language
      and culture to another. Second, this process will be examined using two
      significant case studies: a close analysis of various quotations from Graeco
      Egyptian authors (Pseudo-Democritus, Zosimus of Panopolis, and Synesius) as
      presented in two Arabic dialogues on alchemy, The Tome of Images and The Dialogue
      between Aras and the King Caesar. These sources demonstrate some of the concrete
      textual realities that underlie general patterns of translation and reception.

PMID- 29343190
TI  - Factors affecting effective ventilation during newborn resuscitation: a
      qualitative study among midwives in rural Tanzania.
AB  - BACKGROUND: Intrapartum-related hypoxia accounts for 30% of neonatal deaths in
      Tanzania. This has led to the introduction and scaling-up of the Helping Babies
      Breathe (HBB) programme, which is a simulation-based learning programme in
      newborn resuscitation skills. Studies have documented ineffective ventilation of
      non-breathing newborns and the inability to follow the HBB algorithm among
      providers. OBJECTIVE: This study aimed at exploring barriers and facilitators to
      effective bag mask ventilation, an essential component of the HBB algorithm,
      during actual newborn resuscitation in rural Tanzania. METHODS: Eight midwives,
      each with more than one year's working experience in the labour ward, were
      interviewed individually at Haydom Lutheran Hospital, Tanzania. The audio
      recordings were transcribed and translated into English and analysed using
      qualitative content analysis. RESULTS: Midwives reported the ability to monitor
      labour properly, preparing resuscitation equipment before delivery, teamwork and
      frequent ventilation training as the most effective factors in improving actual
      ventilation practices and promoting the survival of newborns. They thought that
      their anxiety and fear due to stress of ventilating a non-breathing baby often
      led to poor resuscitation performance. Additionally, they experienced
      difficulties assessing the baby's condition and providing appropriate clinical
      responses to initial interventions at birth; hence, further necessary actions and
      timely initiation of ventilation were delayed. CONCLUSIONS: Efforts should be
      focused on improving labour monitoring, birth preparedness and accurate
      assessment immediately after birth, to decrease intrapartum-related hypoxia.
      Midwives should be well prepared to treat a non-breathing baby through high
      quality and frequent simulation training with an emphasis on teamwork training.

PMID- 29343191
TI  - Thermophilic xylanases: from bench to bottle.
AB  - Lignocellulosic biomass is a valuable raw material. As technology has evolved,
      industrial interest in new ways to take advantage of this raw material has grown.
      Biomass is treated with different microbial cells or enzymes under ideal
      industrial conditions to produce the desired products. Xylanases are the key
      enzymes that degrade the xylosidic linkages in the xylan backbone of the biomass,
      and commercial enzymes are categorized into different glycoside hydrolase
      families. Thermophilic microorganisms are excellent sources of industrially
      relevant thermostable enzymes that can withstand the harsh conditions of
      industrial processing. Thermostable xylanases display high-specific activity at
      elevated temperatures and distinguish themselves in biochemical properties,
      structures, and modes of action from their mesophilic counterparts. Natural
      xylanases can be further improved through genetic engineering. Rapid progress
      with genome editing, writing, and synthetic biological techniques have provided
      unlimited potential to produce thermophilic xylanases in their natural hosts or
      cell factories including bacteria, yeasts, and filamentous fungi. This review
      will discuss the biotechnological potential of xylanases from thermophilic
      microorganisms and the ways they are being optimized and produced for various
      industrial applications.

PMID- 29343192
TI  - Coverage and outcomes of antenatal tests for infections: a population based
      survey in the Province of Trento, Italy.
AB  - BACKGROUND: Rubella, syphilis, toxoplasmosis, cytomegalovirus (CMV), hepatitis B
      (HBV) and C (HCV), HIV, and Group B Streptococcus (GBS) infections may have very
      severe outcomes during pregnancy, and for this reason, monitoring of infections
      in pregnant women is a requirement of prenatal assistance. AIMS: To describe
      coverage and outcome of the screening for rubella, syphilis, toxoplasmosis, CMV,
      HBV, HCV, HIV, and Group B Streptococcus in pregnancy in the Autonomous Province
      of Trento, Northern Italy (538,600 inhabitants). METHODS: We analysed the
      coverage and outcome of the above-mentioned screenings among women who delivered
      in the hospitals of the Province of Trento between 2007 and 2014 (N = 38,712).
      Screenings were grouped according to characteristics such as recommendation by
      national and local guidelines, scheduling of the tests, operating methods, and
      charge. We also estimated odds ratios (ORs) for missing screening for selected
      infections through multiple logistic regression. RESULTS: Estimated uptake of
      antenatal screening was 99.7% for rubella, 99.3% for syphilis, 99.7% for
      toxoplasmosis, 98.1% for HIV infection, 99.0% for HBV, 98.9% for HCV, 94.0% for
      GBS infection, and 75.4% for CMV infection. The overall prevalence of immunity
      was 94.1% for rubella, 24.2% for toxoplasmosis, and 64.2% for CMV. The rate of
      seroconversion in pregnant women was 0.02% for rubella, 0.29% for toxoplasmosis,
      and 0.75% for CMV. The overall prevalence of infection was 0.94% for HBV, 0.53%
      for HCV, 22.3% for GBS, 0.29% for syphilis, and 0.13% for HIV. We found a
      significant positive association for all screening tests, between lack of testing
      and late first medical examination in pregnancy (ORs ranging from 1.20 to 1.66
      for the first medical visit in the second trimester and ORs ranging from 1.60 to
      5.88 for the first medical visit in third trimester, compared to early medical
      visit in the first trimester). Compared to Italian citizenship, foreign
      citizenship of the mother was also positively associated with absence of
      screening (ORs ranging from 1.30 to 1.53). A significant inverse association was
      observed for calendar year of delivery (ORs ranging from 0.71 to 0.97, for 1 year
      increment). Less educated mothers and pluriparae were also at higher risks of not
      being tested. Analysis of the association with mother age showed different
      heterogeneous effects. CONCLUSIONS: Our study indicates that the attention to
      screening and detecting infected cases is growing over the time. In addition,
      care delivered during pregnancy has a leading role in determining coverage of the
      examinations. Immigrant, pluriparous and less educated women need particular
      attention.

PMID- 29343193
TI  - Perinatal sclerostin concentrations in abnormal fetal growth: the impact of
      gestational diabetes.
AB  - OBJECTIVE: To prospectively evaluate maternal and cord blood concentrations of
      sclerostin - an osteocyte-secreted factor, inhibiting osteoblast differentiation
      and bone formation and associated with adverse metabolism - in pregnancies with
      normal and abnormal fetal growth. METHODS: Plasma sclerostin concentrations were
      determined by ELISA in 80 maternal and 80 cord blood samples from asymmetric
      intrauterine-growth-restricted (IUGR, n = 30), large-for-gestational-age (LGA, n
      = 30), and appropriate-for-gestational-age (AGA, n = 20) singleton full-term
      pregnancies. Fourteen out of 30 mothers with LGA offspring presented with
      gestational diabetes mellitus (GDM). RESULTS: Maternal and fetal sclerostin
      concentrations did not differ among LGA, IUGR, and AGA groups. Fetal
      concentrations were higher than maternal. In LGA group, maternal concentrations
      were elevated in cases of GDM (b = 13.009, 95%CI 1.425-24.593, p = .029). In a
      combined group and the IUGR group, maternal concentrations were elevated in older
      mothers (b = 0.788, 95%CI 0.190-1.385, p = .010, and b = 0.740, 95%CI 0.042
      1.438, p = .039, respectively). CONCLUSIONS: Maternal and fetal sclerostin
      concentrations may not be differentially regulated in pregnancies complicated by
      abnormal fetal growth. Circulating maternal levels are higher in cases of GDM,
      probably implying reduced bone formation. Sclerostin up-regulation with aging may
      be one of the molecular pathways responsible for the observed age-related decline
      in bone synthesis, leading to accelerated bone loss in humans.

PMID- 29343194
TI  - A brain impact stress analysis using advanced discretization meshless techniques.
AB  - This work has the objective to compare the mechanical behaviour of a brain impact
      using an alternative numerical meshless technique. Thus, a discrete geometrical
      model of a brain was constructed using medical images. This technique allows to
      achieve a discretization with realistic geometry, allowing to define locally the
      mechanical properties according to the medical images colour scale. After
      defining the discrete geometrical model of the brain, the essential and natural
      boundary conditions were imposed to reproduce a sudden impact force. The analysis
      was performed using the finite element analysis and the radial point
      interpolation method, an advanced discretization technique. The results of both
      techniques are compared. When compared with the finite element analysis, it was
      verified that meshless methods possess a higher convergence rate and that they
      are capable of producing smoother variable fields.

PMID- 29343195
TI  - Caring for a family member or friend with dementia at the end of life: A scoping
      review and implications for palliative care practice.
AB  - BACKGROUND: Although people with dementia receive substantial care from informal
      sources, there is limited research available that investigates how these carers
      experience end-of-life care. AIM: This review aimed to identify what is currently
      known about carers' experiences of providing end-of-life care to a family member
      or friend with dementia and draw implications for palliative care policy and
      service provision. DESIGN: A scoping literature review was conducted, first using
      a targeted key word search, followed by assessments of eligibility based on title
      and then abstract content. DATA SOURCES: Records were sourced through PsycINFO,
      PubMed and CINAHL databases. Peer-reviewed papers published between 2000 and
      2016, reporting on data collected directly from carers, were included for review.
      RESULTS: Carers' experience centred on relationships (with care recipients,
      family and friends and health care professionals) and the specific context of
      caring for someone with dementia. These broad categories of carers' experiences
      had clear influences on them personally, particularly in relation to their sense
      of self and their wellbeing. CONCLUSION: Palliative care services would benefit
      from ensuring holistic approaches to supporting people with dementia, their
      carers and wider family networks. Tailoring services to the specific context of
      dementia would enable effective, personalised support throughout extended periods
      leading up to care recipient death as well as through the challenges faced beyond
      bereavement.

PMID- 29343196
TI  - Plexiform Vasculopathy in Feline Cervical Lymph Nodes.
AB  - Plexiform vasculopathy refers to an endothelial proliferative disorder affecting
      cervical or inguinal lymph nodes of cats. The cause of this disorder and the
      origin of the proliferating endothelial cells are still unknown. In 4 cats with a
      history of a slowly growing, well-demarcated, nonpainful mass adjacent to the
      thyroid gland, an enlarged dark brown to red lymph node was removed.
      Histologically, the lymph nodes showed severe loss of lymphoid tissue with
      accumulations of erythrocytes. In addition, networks of capillary structures with
      well-differentiated endothelial cells on a collagen-rich stroma were observed,
      consistent with benign plexiform vasculopathy. Immunohistochemistry revealed the
      expression of the vascular endothelial markers CD31 and factor VIII-related
      antigen. In addition, immunolabeling with a Prox-1 antibody indicated a
      lymphendothelial origin. With respect to our findings, a lymphendothelial origin
      has to be considered in cases of intranodal vascular neoplasms.

PMID- 29343197
TI  - Coexpression of CD3 and CD20 in Canine Enteropathy-Associated T-cell Lymphoma.
AB  - The majority of primary intestinal lymphomas in dogs are T-cell lymphomas, with
      enteropathy-associated T-cell lymphoma (EATL) large cell type (type 1) being the
      most common. While most T-cell lymphomas express the T-cell marker CD3, there is
      increasing evidence that some human and canine T-cell lymphomas coexpress the B
      cell marker CD20. We describe 3 cases of CD3+, CD20+, Pax5- EATL type 1 in dogs.
      All 3 cases had clonal rearrangement of T-cell receptor gamma. Initial clinical
      signs included weight loss, inappetence, diarrhea, and/or vomiting. The mean age
      was 9 years (range 3-12). Survival was highly variable ranging from 20 days to
      longer than 1.6 years. Considering the different chemotherapeutic response of T
      cell versus B-cell lymphomas, accurate diagnosis of lymphomas coexpressing CD3
      and CD20 as EATL type 1 based on histologic features and clonality results is
      important. Regardless, the clinical and/or prognostic significance of neoplastic
      T cells expressing CD20 is unclear.

PMID- 29343198
TI  - Localization of Felis catus Papillomavirus Type 2 E6 and E7 RNA in Feline
      Cutaneous Squamous Cell Carcinoma.
AB  - Findings from polymerase chain reaction-based methods have suggested a role of
      Felis catus papillomavirus 2 (FcaPV-2) in the development of feline cutaneous
      squamous cell carcinoma (SCC). However, because polymerase chain reaction cannot
      localize deoxyribonucleic acid or ribonucleic acid within the lesion, it is
      difficult to differentiate a coincidental FcaPV-2 infection and a causative
      association. Given that a key event in the pathogenesis of human papillomavirus
      induced cancer is the expression of viral E6 and E7 oncogenes, localization of
      FcaPV-2 E6 and E7 transcription within neoplastic cells in feline SCCs would
      support a causative role for this papillomavirus. Therefore, RNAscope in situ
      hybridization was used to localize FcaPV-2 E6 and E7 transcripts in 18 formalin
      fixed paraffin-embedded samples of cutaneous SCC. Positive signals were present
      within 5 of 9 samples (56%) from ultraviolet-protected sites and 0 of 9 samples
      from ultraviolet-exposed sites. In the 4 in situ hybridization-positive samples
      that contained adjacent hyperplastic skin, hybridization patterns in these
      regions were characterized by intense nuclear signals within the superficial
      epidermis and punctate signals within the basal epithelial layers. However,
      within the 5 SCCs, punctate signals were present within all layers of the
      epidermis, with progressive loss of intense nuclear signals within the
      superficial epidermis. This hybridization pattern is consistent with unregulated
      E6 and E7 transcription and decreased viral replication and is similar to the
      pattern observed in human papillomavirus-induced cancers as they progress from
      hyperplastic lesions containing productive infections to nonproductive neoplasms.
      These findings support a causative role for FcaPV-2 in the pathogenesis of feline
      SCC.

PMID- 29343199
TI  - CD204-Expressing Tumor-Associated Macrophages Are Associated With Malignant, High
      Grade, and Hormone Receptor-Negative Canine Mammary Gland Tumors.
AB  - Tumor-associated macrophages (TAMs) are an important component of leukocyte
      infiltration in tumors. TAMs can be classified into M1 and M2 phenotypes. In the
      present study, the expression of CD204, an M2-polarized macrophage receptor, was
      investigated by immunohistochemistry in the area surrounding TAMs in 101 cases of
      canine mammary gland tumor (CMT). We examined the relationship between M2
      polarized TAMs and malignancy, histological subtype, histological grade,
      molecular subtype, hormone receptor (HR) status, and clinical obesity indices.
      The mean number of CD204-positive macrophages was significantly higher in
      malignant CMTs than in benign CMTs ( P = .000). The number of CD204-positive
      macrophages differed significantly between histological grades ( P = .000) and
      were significantly higher in grade III than in grades I and II. Moreover, the
      mean number of CD204-positive macrophages was significantly higher in HR-negative
      malignant CMTs than in HR-positive malignant CMTs ( P = .035) and in malignant
      CMTs with lymphatic invasion compared to malignant CMTs without lymphatic
      invasion ( P = .000). These findings suggest that CD204-positive macrophages
      might affect the development and behavior of CMTs and highlight the potential of
      CD204 as a prognostic factor.

PMID- 29343200
TI  - Immunohistochemical Expression of CD31 (PECAM-1) in Nonendothelial Tumors of
      Dogs.
AB  - CD31 immunoreactivity has been reported in human nonendothelial tumors of both
      epithelial and mesenchymal origin. This study examined CD31 immunoreactivity of
      347 formalin-fixed, paraffin-embedded normal, nonneoplastic, and neoplastic
      canine tissues. CD31 expression was considered positive if at least 10% of the
      cell population had membranous reactivity. Labeling with the CD31 antibody (clone
      JC/70A) was observed in 16 samples of normal organs (liver, kidney, lymph node),
      6 of 6 specimens of hepatic nodular hyperplasia, 3 of 3 hepatic regenerative
      nodules, 1 of 4 anal sac carcinomas, 6 of 6 hemangiosarcomas, 18 of 20
      hepatocellular carcinomas, 1 of 6 mammary carcinomas, 3 of 5 plasmacytomas, 18 of
      53 renal cell carcinomas, and 1 of 5 cutaneous histiocytomas. CD31 expression did
      not correlate with case outcome in hepatocellular or renal cell carcinomas.
      Although distinguishing hemangiosarcoma from other neoplasms is typically
      straightforward, pathologists should be aware of potential cross-reactivity when
      relying on CD31 immunohistochemistry for diagnosis, particularly in small biopsy
      samples or when faced with an epithelioid or poorly differentiated vascular
      neoplasm.

PMID- 29343201
TI  - The impact of blackcurrant juice on attention, mood and brain wave spectral
      activity in young healthy volunteers.
AB  - There is a growing body of evidence from randomized controlled trials which
      indicates that consumption of berries has a positive effect upon the cognitive
      function of healthy adults. It has been recommended that studies combining
      cognitive and physiological measures be undertaken in order to strengthen the
      evidence base for the putative effects of flavonoid consumption on cognitive
      outcomes. This pilot study utilized a randomized, double-blind and placebo
      controlled crossover design to assess the influence of the acute administration
      of anthocyanin-rich blackcurrant juice, standardized at 500 mg of polyphenols, on
      mood and attention. Additionally, this trial used electroencephalography (EEG) to
      assess if any changes in cognitive performance are associated with changes in
      localized prefrontal cortex neuronal activity in nine healthy young adults.
      Outcomes from the pilot EEG data highlight an anxiolytic effect of the
      consumption of a single serve blackcurrant juice, as indexed by a suppression of
      alpha spectral power, and an increase in the slow wave delta and theta spectral
      powers. There was also an indication of greater alertness and lower fatigue, as
      indexed by an increase in beta power and suppression of alpha spectral power.
      Outcomes from the CogTrackTM system indicated a small acute increase in reaction
      times during the digit vigilance task.

PMID- 29343202
TI  - Pillars of wisdom: ankylosing spondylitis in pocket format from the master.

PMID- 29343203
TI  - Cognition, Health-Related Quality of Life, and Depression Ten Years after
      Moderate to Severe Traumatic Brain Injury: A Prospective Cohort Study.
AB  - The aim of this study was to evaluate cognitive function 10 years after moderate
      severe traumatic brain injury (TBI) and to investigate the associations among
      cognitive function, depression, and health-related quality of life (HRQoL). In
      this prospective cohort study, with measurements at 3, 6, 12, 18, 24, 36, and 120
      months post-TBI, patients 18-67 years of age (n = 113) with moderate-severe TBI
      were recruited. Main outcome measures were depression (Center for Epidemiologic
      Studies-Depression Scale [CES-D]), subjective cognitive functioning (Cognitive
      Failure Questionnaire [CFQ]), objective cognitive functioning, and HRQoL (Medical
      Outcomes Study 36-Item Short Form Health Survey [SF-36]). Fifty of the initial
      113 patients completed the 10 year follow-up. Twenty percent showed symptoms of
      depression (CES-D >= 16). These patients had more psychiatric symptoms at
      hospital discharge (p = 0.048) and were more often referred to rehabilitation or
      nursing homes (p = 0.015) than non-depressed patients. Further, they also had
      significantly lower scores in six of the eight subdomains of the SF-36. The non
      depressed patients had equivalent scores to those of the Dutch norm-population on
      all subdomains of the SF-36. Cognitive problems at hospital discharge were
      related with worse cognitive outcome 10 years post-TBI, but not with depression
      or HRQoL. Ten years after moderate-severe TBI, only weak associations (p < 0.05)
      between depression scores and two objective cognitive functioning scores were
      found. However, there were moderate associations (p < 0.01) among depression
      scores, HRQoL, and subjective cognitive functioning. Therefore, signaling and
      treatment of depressive symptoms after moderate-severe TBI may be of major
      importance for optimizing HRQoL in the long term. We did not find strong evidence
      for associations between depression and objective cognitive functioning in the
      long term post-TBI. Disease awareness and selective dropping out may play a role
      in long-term follow-up studies in moderate-severe TBI. More long-term research is
      needed in this field.

PMID- 29343204
TI  - Automatic Intracranial Segmentation: Is the Clinician Still Needed?
AB  - INTRODUCTION: Stereotactic hypofractionated radiotherapy is an effective
      treatment for brain metastases in oligometastatic patients. Its planning is
      however time-consuming because of the number of organs at risk to be manually
      segmented. This study evaluates 2 automated segmentation commercial software.
      METHODS: Patients were scanned in the treatment position. The computed tomography
      scan was registered on a magnetic resonance imaging and volumes were manually
      segmented by a clinician. Then 2 automated segmentations were performed (with
      iPlan and Smart Segmentation). RT STRUCT files were compared with Aquilab's
      Artistruct segment comparison module. We selected common segmented volume ratio
      as the main judging criterion. Secondary criteria were Dice-Sorensen
      coefficients, overlap ratio, and additional segmented volume. RESULTS: Twenty
      consecutive patients were included. Agreement between manual and automated
      contouring was poor. Common segmented volumes ranged from 7.71% to 82.54%, Dice
      Sorensen coefficient ranged from 0.0745 to 0.8398, overlap ratio ranged from
      0.0414 to 0.7275, and additional segmented volume ranged from 9.80% to 92.25%.
      Each software outperformed the other on some organs while performing worse on
      others. CONCLUSION: No software seemed clearly better than the other. Common
      segmented volumes were much too low for routine use in stereotactic
      hypofractionated brain radiotherapy. Manual editing is still needed.

PMID- 29343205
TI  - A Network Meta-Analysis on the Diagnostic Value of Different Imaging Methods for
      Lymph Node Metastases in Patients With Cervical Cancer.
AB  - PURPOSE: We performed this network meta-analysis to compare the diagnostic value
      of 4 imaging methods (magnetic resonance imaging, positron emission tomography,
      computed tomography, and diffusion-weighted imaging) for diagnosing lymph node
      metastases in cervical cancer. METHOD: Diagnostic tests regarding different
      imaging methods to diagnose lymph node metastases in cervical cancer were
      retrieved from the Cochrane Library, PubMed, and Embase electronic databases from
      inception to December 2016. Direct and indirect evidence was performed to
      calculate the odds ratio and to draw the surface under the cumulative ranking
      curves of the 4 imaging methods for diagnosing lymph node metastases in cervical
      cancer. RESULTS: Sixteen eligible diagnostic tests were included in this network
      meta-analysis. The results of network meta-analysis demonstrate that in
      comparison with the diffusion-weighted imaging, positive likelihood ratio,
      negative likelihood ratio, and diagnostic odds ratio of positron emission
      tomography were relatively higher. Additionally, the results further indicate
      that compared with other diagnosis method, positive likelihood ratio, negative
      likelihood ratio, and diagnostic odds ratio of positron emission tomography had a
      higher trend. The surface under the cumulative ranking curve results indicated
      that in terms of positive likelihood ratio and diagnostic odds ratio, positron
      emission tomography had a relatively higher diagnostic value for lymph node
      metastases in patients with cervical cancer. CONCLUSION: Our findings indicate
      that positron emission tomography might have a relatively higher diagnostic value
      for lymph node metastases in patients with cervical cancer.

PMID- 29343206
TI  - Line-Enhanced Deformable Registration of Pulmonary Computed Tomography Images
      Before and After Radiation Therapy With Radiation-Induced Fibrosis.
AB  - PURPOSE: The deformable registration of pulmonary computed tomography images
      before and after radiation therapy is challenging due to anatomic changes from
      radiation fibrosis. We hypothesize that a line-enhanced registration algorithm
      can reduce landmark error over the entire lung, including the irradiated regions,
      when compared to an intensity-based deformable registration algorithm. MATERIALS:
      Two intensity-based B-spline deformable registration algorithms of pre-radiation
      therapy and post-radiation therapy images were compared. The first was a control
      intensity-based algorithm that utilized computed tomography images without
      modification. The second was a line enhancement algorithm that incorporated a
      Hessian-based line enhancement filter prior to deformable image registration.
      Registrations were evaluated based on the landmark error between user-identified
      landmark pairs and the overlap ratio. RESULTS: Twenty-one patients with pre
      radiation therapy and post-radiation therapy scans were included. The median time
      interval between scans was 1.2 years (range: 0.3-3.3 years). Median landmark
      errors for the line enhancement algorithm were significantly lower than those for
      the control algorithm over the entire lung (1.67 vs 1.83 mm; P < .01), as well as
      within the 0 to 5 Gy (1.40 vs 1.57; P < .01) and >5 Gy (2.25 vs 3.31; P < .01)
      dose intervals. The median lung mask overlap ratio for the line enhancement
      algorithm (96.2%) was greater than that for the control algorithm (95.8%; P <
      .01). Landmark error within the >5 Gy dose interval demonstrated a significant
      inverse relationship with post-radiation therapy fibrosis enhancement after line
      enhancement filtration (Pearson correlation coefficient = -0.48; P = .03).
      CONCLUSION: The line enhancement registration algorithm is a promising method for
      registering images before and after radiation therapy.

PMID- 29343207
TI  - Genome-Wide Analysis Identified a Number of Dysregulated Long Noncoding RNA
      (lncRNA) in Human Pancreatic Ductal Adenocarcinoma.
AB  - BACKGROUND: Long noncoding RNAs have been shown to play crucial roles in cancer
      biology, while the long noncoding RNA landscapes of pancreatic ductal
      adenocarcinoma have not been completely characterized. We aimed to determine
      whether long noncoding RNA could serve as early diagnostic biomarkers for
      pancreatic ductal adenocarcinoma. METHOD: We conducted a genome-wide microarray
      analysis on pancreatic ductal adenocarcinoma and their adjacent noncancerous
      tissues from 8 Chinese patients. RESULTS: A total of 3352 significantly
      differentially expressed long noncoding RNAs were detected. Of total, 1249 long
      noncoding RNAs were upregulated and 2103 were downregulated (fold change >=2, P <
      0.05, FDR <0.05). These differentially expressed long noncoding RNAs were not
      evenly distributed among chromosomes in human genome. Hierarchical clustering of
      these differentially expressed long noncoding RNAs revealed large variabilities
      in long noncoding RNA expression among individual patient, indicating that
      certain long noncoding RNAs could play a unique role or be used as a biomarker
      for specific subtype of pancreatic ductal adenocarcinoma. Gene Ontology
      enrichment and pathway analysis identified several remarkably dysregulated
      pathways in pancreatic ductal adenocarcinoma tissue, such as interferon-gamma
      mediated signaling pathway, mitotic cell cycle and proliferation, extracellular
      matrix receptor interaction, focal adhesion, and regulation of actin
      cytoskeleton. The co-expression network analysis detected 393 potential
      interactions between 80 differentially expressed long noncoding RNAs and 105
      messenger RNAs. We experimentally verified 7 most markedly dysregulated long
      noncoding RNAs from the network. CONCLUSION: Our study provided a genome-wide
      survey of dysregulated long noncoding RNAs and long noncoding RNA/messenger RNA
      co-regulation networks in pancreatic ductal adenocarcinoma tissue. These
      dysregulated long noncoding RNA/messenger RNA networks could be used as
      biomarkers to provide early diagnosis of pancreatic ductal adenocarcinoma or its
      subtype, predict prognosis, and evaluate treatment efficacy.

PMID- 29343208
TI  - Lapatinib Inhibits Breast Cancer Cell Proliferation by Influencing PKM2
      Expression.
AB  - Pyruvate kinase type M2, which is expressed in multiple tumor cell types and
      plays a key role in aerobic glycolysis, also has nonglycolytic functions and can
      regulate transcription and cell proliferation. The results of this study show
      that epidermal growth factor receptor activation induces pyruvate kinase type M2
      nuclear translocation. To further determine the relationship between pyruvate
      kinase type M2 and epidermal growth factor receptor, we analyzed pathological
      data from mammary glands and performed epidermal growth factor receptor/human
      epidermal growth factor receptor 2 knockdown to reveal that pyruvate kinase type
      M2 is associated with epidermal growth factor receptor and human epidermal growth
      factor receptor 2. Lapatinib is a small molecule epidermal growth factor receptor
      tyrosine kinase inhibitor that can inhibit epidermal growth factor receptor and
      human epidermal growth factor receptor 2, though its effect on pyruvate kinase
      type M2 remains elusive. Accordingly, we performed Western blotting and reverse
      transcription polymerase chain reaction and analyzed pathological data from
      mammary glands, with results suggesting that lapatinib inhibits pyruvate kinase
      type M2 expression. We further found that the antitumor drug lapatinib inhibits
      breast cancer cell proliferation by influencing pyruvate kinase type M2
      expression, as based on Cell Counting Kit-8 analyses and pyruvate kinase type M2
      overexpression experiments. Signal transducer and activator of transcription 3,
      which is a transcription factor-associated cell proliferation and the only
      transcription factor that interacts with pyruvate kinase type M2, we performed
      pyruvate kinase type M2 knockdown experiments in Human breast cancer cells MDA-MB
      231 and Human breast cancer cells SK-BR-3 cell lines and examined the effect on
      levels of Signal transducer and activator of transcription 3 and phosphorylated
      Signal transducer and activator of transcription 3. The results indicate that
      pyruvate kinase type M2 regulates Signal transducer and activator of
      transcription 3 and phospho-Stat3 (Tyr705) expression. Together with previous
      reports, our findings show that lapatinib inhibits breast cancer cell
      proliferation by influencing pyruvate kinase type M2 expression, which results in
      a reduction in both Signal transducer and activator of transcription 3 and
      phosphorylated Signal transducer and activator of transcription 3.

PMID- 29343210
TI  - Prediction of structural consequences for disease causing variants in C21orf2
      protein using computational approaches.
AB  - Amyotrophic lateral sclerosis (ALS), a progressive motor-neurone disease, affects
      individuals usually aged between 50 and 70 years. C21orf2, recently identified as
      the new ALS susceptibility gene, harbours rare missense mutations that cause this
      fatal disease. We used bioinformatics and molecular modelling approaches to study
      specific ALS-associated mutations in C21orf2. Both native and mutant structures
      of the protein obtained from homology modelling were analysed in detail to gain
      insights into the potential impact of these mutations on the protein structure
      and its function. Our analyses reveal that more than 75% of the mutations are
      likely to be deleterious. These effects seem to carry through to mouse C21orf2 as
      well, indicating that mouse would make a viable animal model to study this ALS
      gene in detail.

PMID- 29343209
TI  - Mild Blast Injury Produces Acute Changes in Basal Intracellular Calcium Levels
      and Activity Patterns in Mouse Hippocampal Neurons.
AB  - Mild traumatic brain injury (mTBI) represents a serious public health concern.
      Although much is understood about long-term changes in cell signaling and
      anatomical pathologies associated with mTBI, little is known about acute changes
      in neuronal function. Using large scale Ca2+ imaging in vivo, we characterized
      the intracellular Ca2+ dynamics in thousands of individual hippocampal neurons
      using a repetitive mild blast injury model in which blasts were directed onto the
      cranium of unanesthetized mice on two consecutive days. Immediately following
      each blast event, neurons exhibited two types of changes in Ca2+ dynamics at
      different time scales. One was a reduction in slow Ca2+ dynamics that
      corresponded to shifts in basal intracellular Ca2+ levels at a time scale of
      minutes, suggesting a disruption of biochemical signaling. The second was a
      reduction in the rates of fast transient Ca2+ fluctuations at the sub-second time
      scale, which are known to be closely linked to neural activity. Interestingly,
      the blast-induced changes in basal Ca2+ levels were independent of the changes in
      the rates of fast Ca2+ transients, suggesting that blasts had heterogeneous
      effects on different cell populations. Both types of changes recovered after ~1
      h. Together, our results demonstrate that mTBI induced acute, heterogeneous
      changes in neuronal function, altering intracellular Ca2+ dynamics across
      different time scales, which may contribute to the initiation of longer-term
      pathologies.

PMID- 29343211
TI  - PAX6 Alternative Splicing and Corneal Development.
AB  - Paired box protein 6 (PAX6) is a master regulator of the eye development. Over
      the last past two decades, our understanding of eye development, especially the
      molecular function of PAX6, has focused on transcriptional control of the Pax6
      expression. However, other regulatory mechanisms for gene expression, including
      alternative splicing (AS), have been understudied in the eye development. Recent
      findings suggest that two PAX6 isoforms generated by AS of Pax6 pre-mRNA may play
      previously underappreciated role(s) during eye development, especially, the
      corneal development.

PMID- 29343212
TI  - Clinical Characteristics of Subtypes of Follicular Variant Papillary Thyroid
      Carcinoma.
AB  - BACKGROUND: Among follicular variant papillary thyroid carcinomas (FVPTCs), the
      noninvasive encapsulated subtype has an excellent prognosis. For this reason,
      reclassification of noninvasive encapsulated FVPTC (EFVPTC) as a new entity
      called "noninvasive follicular thyroid neoplasm with papillary-like nuclear
      features" (NIFTP) has been proposed, but controversy remains. To characterize
      noninvasive EFVPTC in an Asian population, the clinicopathologic features of each
      FVPTC subtype were compared in a Korean population. METHODS: FVPTC patients (n =
      142) who underwent thyroidectomy between 2009 and 2014, and whose tumor size was
      >1 cm, were included in the study. The surgical pathology of each patient was
      reevaluated by two independent expert pathologists. RESULTS: The percentages of
      noninvasive and invasive EFVPTC and infiltrative FVPTC (IFVPTC) in the study were
      30%, 31%, and 39%, respectively. There was no difference in preoperative
      cytological diagnosis or the extent of surgery between noninvasive and invasive
      EFVPTC. However, the proportion of Bethesda category IV was lower in IFVPTC (16%)
      than in noninvasive and invasive EFVPTC (35% and 36%, respectively). Therefore,
      thyroid lobectomy was more common in noninvasive or invasive EFVPTC (54% or 48%,
      respectively) than in IFVPTC (16%). Noninvasive EFVPTC showed lower multiplicity,
      extrathyroidal extension, and BRAFV600E mutation frequency (three cases; 8%) than
      did invasive EFVPTC, but other pathological characteristics were similar.
      However, IFVPTC showed significant differences in tumor size, extrathyroidal
      extension, lymph node metastasis, Tumor Node Metastasis stage, and American
      Thyroid Association high-risk category compared with noninvasive and invasive
      EFVPTC. In the noninvasive EFVPTC group, there were six (14%) cases with
      multifocality and three (7%) cases with lymph node metastasis. However, only two
      cases with multifocality and one case with lymph node metastasis originated from
      noninvasive FVPTC, while the other cases were from coexisting conventional PTCs.
      CONCLUSIONS: Noninvasive EFVPTC has favorable pathological features, but lymph
      node metastasis or BRAFV600E mutations were observed in some patients. Therefore,
      in order for the distinction between noninvasive EFVPTC and invasive EFVPTC to
      have more clinical significance, the criteria for NIFTP need to be more strictly
      revised.

PMID- 29343213
TI  - The community is just a small circle: citizen participation in the free maternal
      and child healthcare programme of Enugu State, Nigeria.
AB  - BACKGROUND: There is a gap in knowledge about how citizen participation impacts
      governance of free healthcare policies for universal health coverage in low- and
      middle-income countries. OBJECTIVE: This study provides evidence about how social
      accountability initiatives influenced revenue generation, pooling and fund
      management, purchasing and capacity of health facilities implementing the free
      maternal and child healthcare programme (FMCHP) in Enugu State, Nigeria. METHODS:
      The study adopted a descriptive, qualitative case-study design to explore how
      social accountability influenced implementation of the FMCHP at the state level
      and in two health districts (Isi-Uzo and Enugu Metropolis) in Enugu State. Data
      were collected from policymakers (n = 16), providers (n = 16) and health facility
      committee leaders (n = 12) through in-depth interviews. We also conducted focus
      group discussions (n = 4) with 42 service users and document review. Data were
      analysed using thematic analysis. RESULTS: It was found that health facility
      committees (HFCs) have not been involved in the generation of funds, fund
      management and tracking of spending in FMCHP. The HFCs did not also seem to have
      increased transparency of benefits and payment of providers. The HFCs emerged as
      the dominant social accountability initiative in FMCHP but lacked power in the
      governance of free health services. The HFCs were constrained by weak legal
      framework, ineffectual FMCHP committees at the state and district levels,
      restricted financial information disclosure, distrustful relationships with
      policymakers and providers, weak patient complaint system and low use of service
      charter. CONCLUSION: The HFCs have not played a significant role in health
      financing and service provision in FMCHP. The gaps in HFCs' participation in
      health financing functions and service delivery need to be considered in the
      design and implementation of free maternal and child healthcare policies that aim
      to achieve universal health coverage.

PMID- 29343214
TI  - Establishing a genetic link between FTO and VDR gene polymorphisms and obesity in
      the Emirati population.
AB  - BACKGROUND: Obesity is a metabolic disease that is widely prevalent with
      approximately 600 million people classified as obese worldwide. Its etiology is
      multifactorial and involves a complex interplay between genes and the
      environment. Over the past few decades, obesity rates among the Emirati
      population have been increasing. The aim of this study was to investigate the
      association of candidate gene single nucleotide polymorphisms (SNPs), namely FTO
      (rs9939609) and VDR (rs1544410), with obesity in the UAE population. METHODS:
      This is a case-control study in which genomic DNA was extracted from saliva
      samples of 201 obese, 115 overweight, and 98 normal subjects in the United Arab
      Emirates (UAE). Genotyping for the variants was performed using TaqMan assay.
      RESULTS: The mean Body Mass Index (BMI) +/- SD for the obese, overweight, and
      normal subjects was 35.76 +/- 4.54, 27.53 +/- 1.45, and 22.69 +/- 1.84 kg/m2,
      respectively. Increasing BMI values were associated with increase in values of
      HbA1c, systolic and diastolic blood pressure. There was a significant association
      observed between the FTO SNP rs9939609 and BMI (p = 0.028), with the minor allele
      A having a clear additive effect on BMI values. There was no significant
      association detected between BMI and rs1544410 of VDR. Moreover, significant
      interaction between the FTO rs9939609 and physical activity reduced the "AA"
      genotype effect on increase in BMI (p = 0.027). CONCLUSIONS: Our study findings
      indicate that the minor allele A of the rs9939609 has a significant association
      with increasing BMI values. Moreover, our findings support the fact that
      increasing BMI is associated with increasing risks of other comorbidities such as
      higher blood pressure, poorer glycemic control, and higher triglycerides. In
      addition, physical activity was found to attenuate the effect of the "AA"
      genotype on the predisposition to higher BMI values.

PMID- 29343215
TI  - Women's decision-making processes and the influences on their mode of birth
      following a previous caesarean section in Taiwan: a qualitative study.
AB  - BACKGROUND: Vaginal birth after caesarean (VBAC) is an alternative option for
      women who have had a previous caesarean section (CS); however, uptake is limited
      because of concern about the risks of uterine rupture. The aim of this study was
      to explore women's decision-making processes and the influences on their mode of
      birth following a previous CS. METHODS: A qualitative approach was used. The
      research comprised three stages. Stage I consisted of naturalistic observation at
      33-34 weeks' gestation. Stage II involved interviews with pregnant women at 35-37
      weeks' gestation. Stage III consisted of interviews with the same women who were
      interviewed postnatally, 1 month after birth. The research was conducted in a
      private medical centre in northern Taiwan. Using a purposive sampling, 21 women
      and 9 obstetricians were recruited. Data collection involved in-depth interviews,
      observation and field notes. Constant comparative analysis was employed for data
      analysis. RESULTS: Ensuring the safety of mother and baby was the focus of
      women's decisions. Women's decisions-making influences included previous birth
      experience, concern about the risks of vaginal birth, evaluation of mode of
      birth, current pregnancy situation, information resources and health insurance.
      In communicating with obstetricians, some women complied with obstetricians'
      recommendations for repeat caesarean section (RCS) without being informed of
      alternatives. Others used four step decision-making processes that included
      searching for information, listening to obstetricians' professional judgement,
      evaluating alternatives, and making a decision regarding mode of birth. After
      birth, women reflected on their decisions in three aspects: reflection on birth
      choices; reflection on factors influencing decisions; and reflection on outcomes
      of decisions. CONCLUSIONS: The health and wellbeing of mother and baby were the
      major concerns for women. In response to the decision-making influences, women's
      interactions with obstetricians regarding birth choices varied from passive
      decision-making to shared decision-making. All women have the right to be
      informed of alternative birthing options. Routine provision of explanations by
      obstetricians regarding risks associated with alternative birth options, in
      addition to financial coverage for RCS from National Health Insurance, would
      assist women's decision-making. Establishment of a website to provide women with
      reliable information about birthing options may also assist women's decision
      making.

PMID- 29343216
TI  - An appraisal: how notifiable infectious diseases are reported by Hungarian family
      physicians.
AB  - BACKGROUND: Within the frame of National Epidemiological Surveillance System,
      family physicians have an obligation to report infections and suspicions cases.
      The aim of this study was to evaluate the knowledge, attitudes, daily practice
      and the reporting activities of Hungarian family physicians regarding to
      infectious diseases. METHODS: A self-administered survey was developed, validated
      and used. The survey was completed by family physicians who had taken part in
      continuous medical educational programmes of all Hungarian medical faculties. The
      questionnaire, consisting demographic questions and 10 statements about their
      reporting habits were completed by 347 doctors, 8% of the total number of family
      physicians. The data were processed in a cross-sectional design with general
      linear model. RESULTS: According to the majority of responders, the current
      reporting system works efficiently. Rural physicians were mainly agreed, that
      reporting is not a simply obligation, it is a professional task as well. They
      were less hindered in daily work by reporting activities, waited less for
      laboratory confirmation before reporting, reported suspicious cases more
      frequently. Practitioner's based in urban settlements preferred to await
      laboratory tests before reporting and were hindered less by failures of the
      electronic reporting system. Older physicians trusted more in the recent system
      and they wished to increase the number of reports. Female physicians have higher
      consciousness in epidemiology. They were mostly in agreement that even severe
      infectious diseases can be diagnosed at primary care level and their daily
      practices were less burdened by reporting duties. CONCLUSIONS: Both the
      epidemiological knowledge of general practitioners' and the electronic
      surveillance systems should be improved. There is a need to develope the
      electronic infrastructure of primary care. More and regular control is also
      expected by the health care authorities, beside the synthesis of professional and
      governmental expectations and regulations.

PMID- 29343218
TI  - LocText: relation extraction of protein localizations to assist database
      curation.
AB  - BACKGROUND: The subcellular localization of a protein is an important aspect of
      its function. However, the experimental annotation of locations is not even
      complete for well-studied model organisms. Text mining might aid database
      curators to add experimental annotations from the scientific literature. Existing
      extraction methods have difficulties to distinguish relationships between
      proteins and cellular locations co-mentioned in the same sentence. RESULTS:
      LocText was created as a new method to extract protein locations from abstracts
      and full texts. LocText learned patterns from syntax parse trees and was trained
      and evaluated on a newly improved LocTextCorpus. Combined with an automatic named
      entity recognizer, LocText achieved high precision (P = 86%+/-4). After
      completing development, we mined the latest research publications for three
      organisms: human (Homo sapiens), budding yeast (Saccharomyces cerevisiae), and
      thale cress (Arabidopsis thaliana). Examining 60 novel, text-mined annotations,
      we found that 65% (human), 85% (yeast), and 80% (cress) were correct. Of all
      validated annotations, 40% were completely novel, i.e. did neither appear in the
      annotations nor the text descriptions of Swiss-Prot. CONCLUSIONS: LocText
      provides a cost-effective, semi-automated workflow to assist database curators in
      identifying novel protein localization annotations. The annotations suggested
      through text-mining would be verified by experts to guarantee high-quality
      standards of manually-curated databases such as Swiss-Prot.

PMID- 29343217
TI  - Ceratocystis cacaofunesta genome analysis reveals a large expansion of
      extracellular phosphatidylinositol-specific phospholipase-C genes (PI-PLC).
AB  - BACKGROUND: The Ceratocystis genus harbors a large number of phytopathogenic
      fungi that cause xylem parenchyma degradation and vascular destruction on a broad
      range of economically important plants. Ceratocystis cacaofunesta is a
      necrotrophic fungus responsible for lethal wilt disease in cacao. The aim of this
      work is to analyze the genome of C. cacaofunesta through a comparative approach
      with genomes of other Sordariomycetes in order to better understand the molecular
      basis of pathogenicity in the Ceratocystis genus. RESULTS: We present an analysis
      of the C. cacaofunesta genome focusing on secreted proteins that might constitute
      pathogenicity factors. Comparative genome analyses among five Ceratocystidaceae
      species and 23 other Sordariomycetes fungi showed a strong reduction in gene
      content of the Ceratocystis genus. However, some gene families displayed a
      remarkable expansion, in particular, the Phosphatidylinositol specific
      phospholipases-C (PI-PLC) family. Also, evolutionary rate calculations suggest
      that the evolution process of this family was guided by positive selection.
      Interestingly, among the 82 PI-PLCs genes identified in the C. cacaofunesta
      genome, 70 genes encoding extracellular PI-PLCs are grouped in eight small
      scaffolds surrounded by transposon fragments and scars that could be involved in
      the rapid evolution of the PI-PLC family. Experimental secretome using LC-MS/MS
      validated 24% (86 proteins) of the total predicted secretome (342 proteins),
      including four PI-PLCs and other important pathogenicity factors. CONCLUSION:
      Analysis of the Ceratocystis cacaofunesta genome provides evidence that PI-PLCs
      may play a role in pathogenicity. Subsequent functional studies will be aimed at
      evaluating this hypothesis. The observed genetic arsenals, together with the
      analysis of the PI-PLC family shown in this work, reveal significant differences
      in the Ceratocystis genome compared to the classical vascular fungi, Verticillium
      and Fusarium. Altogether, our analyses provide new insights into the evolution
      and the molecular basis of plant pathogenicity.

PMID- 29343219
TI  - The preliminary effect of whole-body vibration intervention on improving the
      skeletal muscle mass index, physical fitness, and quality of life among older
      people with sarcopenia.
AB  - BACKGROUND: Studies have shown that sarcopenia easily leads to difficulty moving,
      disability, and poor quality of life. However, researches on the use of whole
      body vibration for older adults with sarcopenia living in institutions have been
      lacking. Therefore, the main objective of the present study was to investigate
      the effect of whole-body vibration intervention on improving the skeletal muscle
      mass index, physical fitness, and quality of life of older adults with sarcopenia
      living in institutions. METHODS: This study adopted a quasi-experimental, single
      group, pretest-posttest design. The whole-body vibration intervention was
      performed over a 3-month period, in which the older adults trained 3 times per
      week; each training lasted 60 s with a break of 30 s for 10 repetitions. The
      older adults' skeletal muscle mass index, physical fitness and quality of life
      before and after the intervention of the whole-body vibration was collected.
      Concerning the statistical methods adopted, nonparametric method-based tests were
      employed. RESULTS: According to the results of analysis, after the intervention
      of the 12-week whole-body vibration, the skeletal muscle mass index (z = - 3.621,
      p = 0.000), physical fitness on standing on one foot (z = - 2.447, p = 0.014),
      shoulder-arm flexibility (z = - 3.159, p = 0.002), 8-ft up and go test (z = -
      2.692, p = 0.009), hand grip strength (z = - 3.388, p = 0.009), and five repeated
      sit-to-stand tests (z = - 2.936, p = 0.003), all improved significantly.
      Furthermore, concerning the quality of life of the older adults in the pretest
      and posttest, the improvements were statistically significant (z = - 2.533, p =
      0.011). CONCLUSIONS: The study results showed the effect of whole-body vibration
      intervention on improving the skeletal muscle mass index, physical fitness, and
      quality of life of sarcopenic older people living in institutions and could serve
      as a crucial reference to health care professionals.

PMID- 29343221
TI  - A case of molecularly profiled extraneural medulloblastoma metastases in a child.
AB  - BACKGROUND: Extraneural metastases are relatively rare manifestations of
      medulloblastoma. CASE PRESENTATION: We present the case of a young boy with group
      three MYCN-amplified medulloblastoma. He received multimodal chemotherapy
      consisting of gross total resection followed by postoperative craniospinal
      radiation and adjuvant chemotherapy. The patient developed extraneural metastases
      4 months after the end of therapy. Literature review identifies the poor
      prognosis of MYCN-amplified medulloblastomas as well as extraneural metastases;
      we review the current limitations and future directions of medulloblastoma
      treatment options. CONCLUSION: To the best of our knowledge, this is the first
      molecularly characterized report of extraneural metastases of medulloblastoma in
      a child.

PMID- 29343220
TI  - Antimicrobial resistance of Neisseria gonorrhoeae in Germany: low levels of
      cephalosporin resistance, but high azithromycin resistance.
AB  - BACKGROUND: The widespread antimicrobial resistance of Neisseria gonorrhoeae is a
      serious problem for the treatment and control of gonorrhoea. Many of the
      previously effective therapeutic agents are no longer viable. Because N.
      gonorrhoeae infections are not reportable in Germany, only limited data on
      disease epidemiology and antimicrobial susceptibility patterns are available. The
      Gonococcal Resistance Network (GORENET) is a surveillance project to monitor
      trends in the antimicrobial susceptibility of N. gonorrhoeae in Germany in order
      to guide treatment algorithms and target future prevention strategies. METHODS:
      Between April 2014 and December 2015, data on patient-related information were
      collected from laboratories nationwide, and susceptibility testing was performed
      on 537 N. gonorrhoeae isolates forwarded from the network laboratories to the
      Conciliar Laboratory for gonococci. Susceptibility results for cefixime,
      ceftriaxone, azithromycin, ciprofloxacin and penicillin were defined according to
      EUCAST 4.0 standards. Percentages, medians and interquartile ranges (IQR) were
      calculated. RESULTS: Altogether, 90% of isolates were from men. The median age
      was 32 (IQR 25-44) years for men and 25 (IQR 22-40) years for women (p-value <
      0.001). The most frequently tested materials among men were urethral (96.1%) and
      rectal swabs (1.7%), and among women, it was mainly endocervical and vaginal
      swabs (84.3%). None of the isolates were resistant to ceftriaxone. Furthermore,
      1.9% (in 2014) and 1.4% (in 2015) of the isolates were resistant to cefixime,
      11.9% and 9.8% showed resistance against azithromycin, 72.0% and 58.3% were
      resistant to ciprofloxacin, and 29.1% and 18.8% were resistant to penicillin.
      CONCLUSIONS: Resistance to ceftriaxone was not detected, and the percentage of
      isolates with resistance to cefixime was low, whereas azithromycin resistance
      showed high levels during the observation period. The rates of ciprofloxacin
      resistance and penicillin resistance were very high across Germany. Continued
      surveillance of antimicrobial drug susceptibilities for N. gonorrhoeae remains
      highly important to ensure efficient disease management.

PMID- 29343222
TI  - Transscleral tunnel incision related arterial hemorrhage in 23-gauge Vitrectomy:
      case report.
AB  - BACKGROUND: Transscleral tunnel incisions are commonly made to avoid
      postoperative leakage in small gauge sutureless vitrectomy. We present an
      unreported intraoperative complication, tunnel incision related arterial
      hemorrhage from sclerotomy, in 23-gauge (23G) vitrectomy. CASE PRESENTATION: Two
      cases of intraocular arterial hemorrhage from superonasal sclerotomy were
      observed at the beginning of vitrectomy. The bleeding filled the vitreous cavity
      quickly and gushed out from the incision port after the involved supronasal
      cannula was removed. The active bleeding seemed not to stop spontaneously. We
      controlled the active bleeding by relocating the involved cannula, elevating the
      intraocular pressure and compressing the sclera wound. Post-operative intraocular
      hemorrhage from the sclerotomy was not found in any of the two cases.
      CONCLUSIONS: We suggest that the bleeding was from injured ciliary artery when
      the incision crossed 3 or 9 o'clock accidently. Surgeons might avoid this
      complication by locating the superior incisions away from the horizontal axis,
      and should be aware the proper management.

PMID- 29343223
TI  - The impact of age on the implementation of evidence-based medications in patients
      with coronary artery disease and its prognostic significance: a retrospective
      cohort study.
AB  - BACKGROUND: Elderly patients with coronary artery disease (CAD) frequently
      complicated with more cardiovascular risk factors, but received fewer evidence
      based medications (EBMs). This study explored the association of EBMs compliance
      in different age groups and the risk of long-term death. METHODS: A retrospective
      analysis was conducted from a single registered database. 2830 consecutive
      patients with CAD were enrolled and grouped into 3 categories by age. The primary
      end point was all-cause mortality and secondary endpoint is cardiovascular
      mortality. RESULTS: The mean follow-up time was 30.25 +/- 11.89 months and death
      occurred in 270 cases,including 150 cases of cardiac death. Cumulative survival
      curves indicated that the incidence rates of all-cause death and cardiovascular
      death increased with age (older than 75 years old vs. 60 to 75 years old vs.
      younger than 60 years old, mortality: 18.7% vs. 9.6% vs. 4.1%, p < 0.001;
      cardiovascular mortality: 10.3% vs. 5.1% vs. 2.7%, p < 0.001). The percentage of
      elderly patients using no EBMs was significantly higher than the percentages in
      the other age group (7.7% vs. 4.6% vs. 2.2%,p < 0.05). Cox regression analysis
      revealed the benefit of combination EBMs (all-cause mortality: hazard ratio [HR]
      0.15, 95% CI 0.08-0.27; cardiac mortality: HR 0.08, 95% CI 0.04-0.19) for older
      CAD patients. Similar trends were found about different kinds of EBMs in elderly
      patients. CONCLUSIONS: Elderly patients with CAD had higher risk of death but a
      lower degree of compliance with EBMs usage. Elderly CAD patients could receive
      more clinical benefits by using EBMs.

PMID- 29343224
TI  - Development and validation of self-reported line drawings of the modified
      Beighton score for the assessment of generalised joint hypermobility.
AB  - BACKGROUND: The impracticalities and comparative expense of carrying out a
      clinical assessment is an obstacle in many large epidemiological studies. The
      purpose of this study was to develop and validate a series of electronic self
      reported line drawing instruments based on the modified Beighton scoring system
      for the assessment of self-reported generalised joint hypermobility. METHODS:
      Five sets of line drawings were created to depict the 9-point Beighton score
      criteria. Each instrument consisted of an explanatory question whereby
      participants were asked to select the line drawing which best represented their
      joints. Fifty participants completed the self-report online instrument on two
      occasions, before attending a clinical assessment. A blinded expert clinical
      observer then assessed participants' on two occasions, using a standardised
      goniometry measurement protocol. Validity of the instrument was assessed by
      participant-observer agreement and reliability by participant repeatability and
      observer repeatability using unweighted Cohen's kappa (k). Validity and
      reliability were assessed for each item in the self-reported instrument
      separately, and for the sum of the total scores. An aggregate score for
      generalised joint hypermobility was determined based on a Beighton score of 4 or
      more out of 9. RESULTS: Observer-repeatability between the two clinical
      assessments demonstrated perfect agreement (k 1.00; 95% CI 1.00, 1.00). Self
      reported participant-repeatability was lower but it was still excellent (k 0.91;
      95% CI 0.74, 1.00). The participant-observer agreement was excellent (k 0.96; 95%
      CI 0.87, 1.00). Validity was excellent for the self-report instrument, with a
      good sensitivity of 0.87 (95% CI 0.81, 0.91) and excellent specificity of 0.99
      (95% CI 0.98, 1.00). CONCLUSIONS: The self-reported instrument provides a valid
      and reliable assessment of the presence of generalised joint hypermobility and
      may have practical use in epidemiological studies.

PMID- 29343225
TI  - Health worker knowledge of Integrated Disease Surveillance and Response standard
      case definitions: a cross-sectional survey at rural health facilities in Kenya.
AB  - BACKGROUND: The correct knowledge of standard case definition is necessary for
      frontline health workers to diagnose suspected diseases across Africa. However,
      surveillance evaluations commonly assume this prerequisite. This study assessed
      the knowledge of case definitions for health workers and their supervisors for
      disease surveillance activities in rural Kenya. METHODS: A cross-sectional survey
      including 131 health workers and their 11 supervisors was undertaken in two
      counties in Kenya. Descriptive analysis was conducted to classify the correctness
      of knowledge into four categories for three tracer diseases (dysentery, measles,
      and dengue). We conducted a univariate and multivariable logistic regression
      analyses to explore factors influencing knowledge of the case definition for
      dysentery. RESULTS: Among supervisors, 81.8% knew the correct definition for
      dysentery, 27.3% for measles, and no correct responses were provided for dengue.
      Correct knowledge was observed for 50.4% of the health workers for dysentery,
      only 12.2% for measles, and none for dengue. Of 10 examined factors, the
      following were significantly associated with health workers' correct knowledge of
      the case definition for dysentery: health workers' cadre (aOR 2.71; 95% CI 1.20
      6.12; p = 0.017), and display of case definition poster (aOR 2.24; 95% CI 1.01
      4.98; p = 0.048). Health workers' exposure to the surveillance refresher
      training, supportive supervision and guidelines were not significantly associated
      with the knowledge. CONCLUSION: The correct knowledge of standard case
      definitions was sub-optimal among health workers and their supervisors, which is
      likely to impact the reliability of routine surveillance reports generated from
      health facilities.

PMID- 29343226
TI  - Binge eating disorder and depressive symptoms among females of child-bearing age:
      the Korea Nurses' Health Study.
AB  - BACKGROUND: Most studies regarding the relationship between binge eating disorder
      (BED) and depression have targeted obese populations. However, nurses,
      particularly female nurses, are one of the vocations that face these issues due
      to various reasons including high stress and shift work. This study investigated
      the prevalence of BED and the correlation between BED and severity of self
      reported depressive symptoms among female nurses in South Korea. METHODS:
      Participants were 7,267 female nurses, of which 502 had symptoms of BED. Using
      the propensity score matching (PSM) technique, 502 nurses with BED and 502
      without BED were included in the analyses. Data were analyzed using descriptive
      statistics, Spearman's correlation, and multivariable ordinal logistic regression
      analysis. RESULTS: The proportion of binge eating disorder was 6.90% among the
      nurses, and 81.3% of nurses displayed some levels of depressive symptoms.
      Multivariable ordinal logistic regression analysis revealed that age (40 years
      old and older), alcohol consumption (frequent drinkers), self-rated health, sleep
      problems, and stress were associated with self-reported depression symptoms.
      Overall, after adjusting for confounders, nurses with BED had 1.80 times the risk
      (95% CI = [1.41-2.30]; p-value < 0.001) of experiencing a greater severity of
      self-reported depression symptoms. CONCLUSIONS: Korean female nurse showed a
      higher prevalence of both binge eating disorder and depressive symptoms, and the
      association between the two factors was proven in the study. Therefore, hospital
      management and health policy makers should be alarmed and agreed on both
      examining nurses on such problems and providing organized and systematic
      assistance.

PMID- 29343227
TI  - Associations among maternal pre-pregnancy body mass index, gestational weight
      gain and risk of autism in the Han Chinese population.
AB  - BACKGROUND: Autism is a neurodevelopmental disorder with an unclear etiology. Pre
      pregnancy body mass index (BMI) and gestational weight gain (GWG) have been
      suggested to play a role in the etiology of autism. The current study explores
      the associations among maternal pre-pregnancy BMI, GWG and the risk of autism in
      the Han Chinese population. METHODS: Demographic information, a basic medical
      history and information regarding maternal pre-pregnancy and pregnancy conditions
      were collected from the parents of 705 Han Chinese children with autism and 2236
      unrelated typically developing children. Binary logistic regressions were
      conducted to calculate the odds ratio (OR) for the relationship among pre
      pregnancy BMI, GWG and the occurrence of autism. The interaction between pre
      pregnancy BMI and GWG was analyzed by performing stratification analyses using a
      logistic model. RESULTS: After adjusting for the children's gender, parental age
      and family annual income, excessive GWG was associated with autism risk in the
      entire sample (OR = 1.327, 95% CI: 1.021-1.725), whereas the relationship between
      maternal pre-pregnancy BMI and autism was not significant. According to the
      stratification analyses, excessive GWG increased the risk of autism in
      overweight/obese mothers (OR = 2.468, 95% CI: 1.102-5.526) but not in underweight
      or normal weight mothers. CONCLUSIONS: The maternal pre-pregnancy BMI might not
      be independently associated with autism risk. However, excessive GWG might
      increase the autism risk of offspring of overweight and obese mothers.

PMID- 29343228
TI  - Problematic internet use and psychiatric co-morbidity in a population of Japanese
      adult psychiatric patients.
AB  - BACKGROUND: Many studies reported the high prevalence of problematic internet use
      (PIU) among adolescents (13-50%), and PIU was associated with various psychiatric
      symptoms. In contrast, only a few studies investigated the prevalence among the
      adult population (6%). This study aimed to investigate the prevalence of PIU and
      psychiatric co-morbidity among adult psychiatric patients. METHODS: Three hundred
      thirty-three adult psychiatric patients were recruited over a 3-month period. Two
      hundred thirty-one of them completed the survey (response rate: 69.4%, 231/333;
      Male/Female/Transgender: 90/139/2; mean age = 42.2). We divided participants into
      "normal internet users" and "problematic internet users" using a combination of
      Young's Internet Addiction Test (IAT) and the Compulsive Internet Use Scale
      (CIUS). Demographic data and comorbid psychiatric symptoms were compared between
      the two groups using self-rating scales measuring insomnia (Athens Insomnia
      Scale, AIS), depression (Beck Depression Inventory, BDI), anxiety (State-trait
      Anxiety Inventory, STAI), attention deficit hyperactivity disorder (ADHD) (Adult
      ADHD Self-report Scale, ASRS), autism (Autism Spectrum Quotient, AQ), obsessive
      compulsive disorder (OCD) (Obsessive-Compulsive Inventory, OCI), social anxiety
      disorder (SAD) (Liebowitz Social Anxiety Scale, LSAS), alcohol abuse, and
      impulsivity (Barratt Impulsive Scale, BIS). RESULTS: Among 231 respondents, 58
      (25.1%) were defined as problematic internet users, as they scored high on the
      IAT (40 or more) or CIUS (21 or more). The age of problematic internet users was
      significantly lower than that of normal internet users (p < 0.001, Mann-Whitney U
      test). The problematic internet users scored significantly higher on scales
      measuring sleep problems (AIS, 8.8 for problematic internet users vs 6.3 for
      normal internet users, p < 0.001), depression (BDI, 27.4 vs 18.3, p < 0.001),
      trait anxiety (STAI, 61.8 vs 53.9, p < 0.001), ADHD (ASRS, part A 3.1 vs 1.8 and
      part B 3.5 vs 1.8, p < 0.001), autism (AQ, 25.9 vs 21.6, p < 0.001), OCD (OCI,
      63.2 vs 36.3, p < 0.001), SAD (LSAS, 71.4 vs 54.0, p < 0.001), and impulsivity
      (BIS, 67.4 vs 63.5, p = 0.004). CONCLUSIONS: The prevalence of PIU among adult
      psychiatric patients is relatively high. As previous studies reported in the
      general population, lower age and psychiatric comorbidity were associated with
      PIU among adult psychiatric patients. More research is needed to determine any
      causal relations between PIU and psychopathological illnesses.

PMID- 29343229
TI  - The Colombo Twin and Singleton Follow-up Study: a population based twin study of
      psychiatric disorders and metabolic syndrome in Sri Lanka.
AB  - BACKGROUND: The disease burden related to mental disorders and metabolic syndrome
      is growing in low-and middle-income countries (LMIC). The Colombo Twin and
      Singleton Study (COTASS) is a population-based sample of twins and singletons in
      Colombo, Sri Lanka. Here we present prevalence estimates for metabolic syndrome
      (metS) and mental disorders from a follow-up (COTASS-2) of the original study
      (COTASS-1), which was a mental health survey. METHODS: In COTASS-2, participants
      completed structured interviews, anthropometric measures and provided fasting
      blood and urine samples. Depressive disorder, depressive symptoms, anxiety
      symptoms, post-traumatic stress disorder (PTSD) and hazardous alcohol use were
      ascertained with structured psychiatric screens (Composite International
      Diagnostic Interview (CIDI), Beck Depression Inventory (BDI-II), Generalised
      Anxiety Disorder Questionnaire (GAD-7), PTSD Checklist - Civilian Version (PCL
      C), and Alcohol Use Disorders Identification Test (AUDIT)). We defined metS
      according to the International Diabetes Federation (IDF) criteria and the revised
      National Cholesterol Education Programme Adult Treatment Panel (NCEP ATP III)
      criteria. We estimated the prevalence of psychiatric disorders and metS and metS
      components, and associations with gender, education and age. RESULTS: Two
      thousand nine hundred thirty-four twins and 1035 singletons were followed up from
      COTASS-1 (83.4 and 61.8% participation rate, respectively). Prevalence estimates
      for depressive disorder (CIDI), depressive symptoms (BDI >= 16), anxiety symptoms
      (GAD-7 >= 10) and PTSD (PCL-C DSM criteria) were 3.8, 5.9, 3.6, and 4.5%
      respectively for twins and 3.9, 9.8, 5.1 and 5.4% for singletons. 28.1 and 30.9%
      of male twins and singletons respectively reported hazardous alcohol use.
      Approximately one third met the metS criteria (IDF: 27.4% twins, 44.6%
      singletons; NCEP ATP III: 30.6% twins, 48.6% singletons). The most prevalent
      components were central obesity (59.2% twins, 71.2% singletons) and raised
      fasting blood glucose or diabetes (38.2% twins, 56.7% singletons). CONCLUSION:
      MetS was highly prevalent in twins, and especially high in singletons, whereas
      the prevalence of mental disorders was low, but consistent with local estimates.
      The high levels of raised fasting plasma glucose and central obesity were
      particularly concerning, and warrant national diabetes prevention programmes.

PMID- 29343230
TI  - The SyBil-AA real-time fMRI neurofeedback study: protocol of a single-blind
      randomized controlled trial in alcohol use disorder.
AB  - BACKGROUND: Alcohol Use Disorder is a highly prevalent mental disorder which puts
      a severe burden on individuals, families, and society. The treatment of Alcohol
      Use Disorder is challenging and novel and innovative treatment approaches are
      needed to expand treatment options. A promising neuroscience-based intervention
      method that allows targeting cortical as well as subcortical brain processes is
      real-time functional magnetic resonance imaging neurofeedback. However, the
      efficacy of this technique as an add-on treatment of Alcohol Use Disorder in a
      clinical setting is hitherto unclear and will be assessed in the Systems Biology
      of Alcohol Addiction (SyBil-AA) neurofeedback study. METHODS: N = 100 patients
      with Alcohol Use Disorder will be randomized to 5 parallel groups in a single
      blind fashion and receive real-time functional magnetic resonance imaging
      neurofeedback while they are presented pictures of alcoholic beverages. The
      groups will either downregulate the ventral striatum, upregulate the right
      inferior frontal gyrus, negatively modulate the connectivity between these
      regions, upregulate, or downregulate the auditory cortex as a control region.
      After receiving 3 sessions of neurofeedback training within a maximum of 2 weeks,
      participants will be followed up monthly for a period of 3 months and relapse
      rates will be assessed as the primary outcome measure. DISCUSSION: The results of
      this study will provide insights into the efficacy of real-time functional
      magnetic resonance imaging neurofeedback training in the treatment of Alcohol Use
      Disorder as well as in the involved brain systems. This might help to identify
      predictors of successful neurofeedback treatment which could potentially be
      useful in developing personalized treatment approaches. TRIAL REGISTRATION: The
      study was retrospectively registered in the German Clinical Trials Register
      (trial identifier: DRKS00010253 ; WHO Universal Trial Number (UTN): U1111-1181
      4218) on May 10th, 2016.

PMID- 29343231
TI  - Cementless unicompartmental knee replacement allows early return to normal
      activity.
AB  - BACKGROUND: Physical activity and regular participation in recreational sports
      gain importance in patients' lifestyle after knee arthroplasty. Cementless
      unicompartimental Knee replacement with the Oxford System has been introduced
      into clinical routine. Currently there is no data reporting on the physical
      activity, return to sports rate and quality of live after medial cementless
      Oxford Unicompartimental Knee Replacement (OUKR). METHODS: This retrospective
      cohort study reports on the functional outcome of the first 27 consecutive
      patients (30 knees) that were consecutively treated with a cementless medial OUKR
      between 2007 and 2009 in our hospital. Physical activity and quality of life were
      measured using the Tegner-Score, the UCLA-Activity Score, the Schulthess Clinical
      Activity Questionnaire and the SF-36 Score. The patients' satisfaction with the
      outcome was measured using a visual analogue scale. RESULTS: Mean age at surgery
      was 62.5 years. Patients showed a rapid recovery with 17 out of 27 patients
      returning to sports within 3 months, 24 within 6 months after surgery. The Return
      to-activity-rate was 100%. 10 out of 27 patients showed a high activity level
      (UCLA >=7 points) with a mean postoperative UCLA-Score of 6.1 points.
      CONCLUSIONS: Patients recover rapidly after cementless OUKR with a return to
      sports rate of 100% and patients are able to participate in high impact sports
      disciplines.

PMID- 29343232
TI  - Intravenous dexmedetomidine pre-medication reduces the required minimum alveolar
      concentration of sevoflurane for smooth tracheal extubation in anesthetized
      children: a randomized clinical trial.
AB  - BACKGROUND: It has been known that Dexmedetomidine pre-medication enhances the
      effects of volatile anesthetics, reduces the need of sevoflurane, and facilitates
      smooth extubation in anesthetized children. This present study was designed to
      determine the effects of different doses of intravenous dexmedetomidine pre
      medication on minimum alveolar concentration of sevoflurane for smooth tracheal
      extubation (MACEX) in anesthetized children. METHODS: A total of seventy-five
      pediatric patients, aged 3-7 years, ASA physical status I and II, and undergoing
      tonsillectomy were randomized to receive intravenous saline (Group D0),
      dexmedetomidine 1 MUg?kg-1 (Group D1), or dexmedetomidine 2 MUg?kg-1 (Group D2)
      approximately 10 min before anesthesia start. Sevoflurane was used for anesthesia
      induction and anesthesia maintenance. At the end of surgery, the initial
      concentration of sevoflurane for smooth tracheal extubation was determined
      according to the modified Dixon's "up-and-down" method. The starting sevoflurane
      for the first patient was 1.5% in Group D0, 1.0% in Group D1, and 0.8% in Group
      D2, with subsequent 0.1% up or down in next patient based on whether smooth
      extubation had been achieved or not in current patient. The endotreacheal tube
      was removed after the predetermined concentration had been maintained constant
      for ten minutes. All responses ("smooth" or "not smooth") to tracheal extubation
      and respiratory complications were assessed. RESULTS: MACEX values of sevoflurane
      in Group D2 (0.51 +/- 0.13%) was significantly lower than in Group D1 (0.83 +/-
      0.10%; P < 0.001), the latter being significantly lower than in Group D0 (1.40 +/
      0.12%; P < 0.001). EC95 values of sevoflurane were 0.83%, 1.07%, and 1.73% in
      Group D2, Group D1, and Group D0, respectively. No patient in the current study
      had laryngospasm. CONCLUSION: Dexmedetomidine decreased the required MACEX values
      of sevoflurane to achieve smooth extubation in a dose-dependent manner.
      Intravenous dexmedetomidine 1 MUg?kg-1 and 2 MUg?kg-1 pre-medication decreased
      MACEX by 41% and 64%, respectively. TRIAL REGISTRATION: Chinese Clinical Trial
      Registry (ChiCTR): ChiCTR-IOD-17011601 , date of registration: 09 Jun 2017,
      retrospectively registered.

PMID- 29343233
TI  - Alcohol use and sickness absence due to all causes and mental- or musculoskeletal
      disorders: a nationally representative study.
AB  - BACKGROUND: Previous studies have not distinguished between different alcohol-use
      histories, which could have contributed to the current inconsistent evidence
      regarding the relationship between alcohol use and subsequent sickness absence.
      We thus examined alcohol use and subsequent diagnosis-specific sickness absence
      in groups with different levels of alcohol use, as well as in lifelong
      abstainers, former drinkers, and people with clinical alcohol use disorders.
      METHODS: The data of the population-based Health 2000 Survey (BRIF8901) of 3666
      Finns aged 30-55 were linked with national registers on medically certified
      sickness absences lasting for > 10 working days (long-term) for all causes (2000 
      2010) and for mental or musculoskeletal disorders (2004-2010), as well as with
      registers on pensions and death (2000-2010). Alcohol use was assessed by
      questionnaire. Chronic somatic diseases were evaluated at baseline in a clinical
      examination, and common mental and alcohol use disorders using the Composite
      International Diagnostic Interview (CIDI). Cox regression analyses were conducted
      with censoring for death and retirement from work. RESULTS: During an average 10
      year follow-up, 56.0% of the participants had at least one long-term sickness
      absence period. Compared with light drinkers, those having an alcohol use
      disorder had increased risk of all-cause sickness absence (HR = 1.27; 95% CI =
      1.04 - 1.54) and sickness absence due to mental disorders (HR = 2.16; 95% CI =
      1.39 - 3.35), when somatic and mental disorders as well as demographic, lifestyle
      related and occupational factors at baseline were accounted for. Lifelong
      abstainers did not differ from light drinkers. Also high-volume drinking (HR =
      1.52; 95% CI 1.03 - 2.25) and former drinking (HR = 1.57; 95% CI = 1.15 - 2.15)
      were associated with long-term sickness absence due to mental disorders. Alcohol
      use was not predictive of sickness absence due to musculoskeletal disorders.
      CONCLUSIONS: These results highlight the need to distinguish between former
      drinking and lifelong abstinence, as only former drinking was associated with
      sickness absence. Alcohol use disorder and high-volume drinking were strongly
      predictive of sickness absence due to mental disorders. Identifying people with
      excessive alcohol use e.g. in occupational health care, and mapping and
      supporting their mental health may help in preventing sickness absences.

PMID- 29343234
TI  - From the day they are born: a qualitative study exploring violence against
      children with disabilities in West Africa.
AB  - BACKGROUND: Despite the building evidence on violence against children globally,
      almost nothing is known about the violence children with disabilities in low and
      middle-income countries (LMICs) experience. The prevalence of violence against
      children with disabilities can be expected to be higher in LMICs where there are
      greater stigmas associated with having a child with a disability, less resources
      for families who have children with disabilities, and wider acceptance of the use
      of corporal punishment to discipline children. This study explores violence
      experienced by children with disabilities based on data collected from four
      countries in West Africa- Guinea, Niger, Sierra Leone, and Togo. METHODS: A
      qualitative study design guided data generation with a total of 419 children,
      community members, and disability stakeholders. Participants were selected using
      purposive sampling. Stakeholders shared their observations of or experiences of
      violence against children with disabilities in their community in interviews and
      focus groups. Thematic analysis guided data analysis and identified patterns of
      meaning among participants' experiences. RESULTS: Results illuminate that
      children with disabilities experience violence more than non-disabled children,
      episodes of violence start at birth, and that how children with disabilities
      participate in their communities contributes to their different experiences of
      violence. CONCLUSIONS: The study recommends policy-oriented actions and
      prevention programs that include children and their families in strategizing ways
      to address violence.

PMID- 29343236
TI  - Barriers to timely diagnosis of interstitial lung disease in the real world: the
      INTENSITY survey.
AB  - BACKGROUND: The diagnosis of idiopathic pulmonary fibrosis (IPF) and other
      interstitial lung diseases (ILD) presents significant clinical challenges. To
      gain insights regarding the diagnostic experience of patients with ILD and to
      identify potential barriers to a timely and accurate diagnosis, we developed an
      online questionnaire and conducted a national survey of adults with a self
      reported diagnosis of ILD. METHODS: A pre-specified total of 600 subjects were
      recruited to participate in a 40-question online survey. E-mail invitations
      containing a link to the survey were sent to 16 427 registered members of the
      Pulmonary Fibrosis Foundation. Additionally, an open invitation was posted on an
      online forum for patients and caregivers ( www.inspire.com ). The recruitment and
      screening period was closed once the pre-defined target number of respondents was
      reached. Eligible participants were adult U.S. residents with a diagnosis of IPF
      or a non-IPF ILD. RESULTS: A total of 600 eligible respondents met the
      eligibility criteria and completed the survey. Of these, 55% reported >= 1
      misdiagnosis and 38% reported >= 2 misdiagnoses prior to the current diagnosis.
      The most common misdiagnoses were asthma (13.5%), pneumonia (13.0%), and
      bronchitis (12.3%). The median time from symptom onset to current diagnosis was 7
      months (range, 0-252 months), with 43% of respondents reporting a delay of >= 1
      year and 19% reporting a delay of >= 3 years. Sixty-one percent of respondents
      underwent at least one invasive diagnostic procedure. CONCLUSIONS: While a
      minority of patients with ILD will experience an appropriate and expedient
      diagnosis, the more typical diagnostic experience for individuals with ILD is
      characterized by considerable delays, frequent misdiagnosis, exposure to costly
      and invasive diagnostic procedures, and substantial use of healthcare resources.
      These findings suggest a need for physician education, development of clinical
      practice recommendations, and improved diagnostic tools aimed at improving
      diagnostic accuracy in patients with ILD.

PMID- 29343235
TI  - Comparison of three assembly strategies for a heterozygous seedless grapevine
      genome assembly.
AB  - BACKGROUND: De novo heterozygous assembly is an ongoing challenge requiring
      improved assembly approaches. In this study, three strategies were used to
      develop de novo Vitis vinifera 'Sultanina' genome assemblies for comparison with
      the inbred V. vinifera (PN40024 12X.v2) reference genome and a published
      Sultanina ALLPATHS-LG assembly (AP). The strategies were: 1) a default PLATANUS
      assembly (PLAT_d) for direct comparison with AP assembly, 2) an iterative merging
      strategy using METASSEMBLER to combine PLAT_d and AP assemblies (MERGE) and 3)
      PLATANUS parameter modifications plus GapCloser (PLAT*_GC). RESULTS: The three
      new assemblies were greater in size than the AP assembly. PLAT*_GC had the
      greatest number of scaffolds aligning with a minimum of 95% identity and >=1000
      bp alignment length to V. vinifera (PN40024 12X.v2) reference genome. SNP
      analysis also identified additional high quality SNPs. A greater number of
      sequence reads mapped back with zero-mismatch to the PLAT_d, MERGE, and PLAT*_GC
      (>94%) than was found in the AP assembly (87%) indicating a greater fidelity to
      the original sequence data in the new assemblies than in AP assembly. A de novo
      gene prediction conducted using seedless RNA-seq data predicted > 30,000 coding
      sequences for the three new de novo assemblies, with the greatest number (30,544)
      in PLAT*_GC and only 26,515 for the AP assembly. Transcription factor analysis
      indicated good family coverage, but some genes found in the VCOST.v3 annotation
      were not identified in any of the de novo assemblies, particularly some from  the
      MYB and ERF families. CONCLUSIONS: The PLAT_d and PLAT*_GC had a greater number
      of synteny blocks with the V. vinifera (PN40024 12X.v2) reference genome than AP
      or MERGE. PLAT*_GC provided the most contiguous assembly with only 1.2% scaffold
      N, in contrast to AP (10.7% N), PLAT_d (6.6% N) and Merge (6.4% N). A PLAT*_GC
      pseudo-chromosome assembly with chromosome alignment to the reference genome V.
      vinifera, (PN40024 12X.v2) provides new information for use in seedless grape
      genetic mapping studies. An annotated de novo gene prediction for the PLAT*_GC
      assembly, aligned with VitisNet pathways provides new seedless grapevine specific
      transcriptomic resource that has excellent fidelity with the seedless short read
      sequence data.

PMID- 29343238
TI  - The slowing pace of life expectancy gains since 1950.
AB  - BACKGROUND: New technological breakthroughs in biomedicine should have made it
      easier for countries to improve life expectancy at birth (LEB). This paper
      measures the pace of improvement in the decadal gains of LEB, for the last 60
      years adjusting for each country's starting point of LEB. METHODS: LEB increases
      over the next 10-years for 139 countries between 1950 and 2009 were regressed on
      LEB, GDP, total fertility rate, population density, CO2 emissions, and HIV
      prevalence using country-specific fixed effects and time-dummies. Analysis
      grouped countries into one-of-four strata: LEB < 51, 51 <= LEB < 61, 61 <= LEB <
      71, and LEB >= 71. RESULTS: The rate of increase of LEB has fallen consistently
      since 1950 across all strata. Results hold in unadjusted analysis and in the
      regression-adjusted analysis. LEB decadal gains fell from 4.80 (IQR: 2.98-6.20)
      years in the 1950s to 2.39 (IQR:1.80-2.80) years in the 2000s for the healthiest
      countries (LEB >= 71). For countries with the lowest LEB (LEB < 51), decadal
      gains fell from 7.38 (IQR:4.83-9.25) years in the 1950s to negative 6.82 (IQR: 
      12.95--1.05) years in the 2000s. Multivariate analysis controlling for HIV
      prevalence, GDP, and other covariates shows a negative effect of time on LEB
      decadal gains among all strata. CONCLUSIONS: Contrary to the expectation that
      advances in health technology and spending would hasten improvements in LEB, we
      found that the pace-of-growth of LEB has slowed around the world.

PMID- 29343237
TI  - Subtypes in clinical burnout patients enrolled in an employee rehabilitation
      program: differences in burnout profiles, depression, and recovery/resources
      stress balance.
AB  - BACKGROUND: Burnout is generally perceived a unified disorder with homogeneous
      symptomatology across people (exhaustion, cynicism, and reduced professional
      efficacy). However, increasing evidence points to intra-individual patterns of
      burnout symptoms in non-clinical samples such as students, athletes, healthy, and
      burned-out employees. Different burnout subtypes might therefore exist. Yet,
      burnout subtypes based on burnout profiles have hardly been explored in clinical
      patients, and the samples investigated in previous studies were rather
      heterogeneous including patients with various physical, psychological, and social
      limitations, symptoms, and disabilities. Therefore, the aim of this study is to
      explore burnout subtypes based on burnout profiles in clinically diagnosed
      burnout patients enrolled in an employee rehabilitation program, and to
      investigate whether the subtypes differ in depression, recovery/resources-stress
      balance, and sociodemographic characteristics. METHODS: One hundred three
      patients (66 women, 37 men) with a clinical burnout diagnosis, who were enrolled
      in a 5 week employee rehabilitation program in two specialized psychosomatic
      clinics in Austria, completed a series of questionnaires including the Maslach
      Burnout Inventory - General Survey (MBI-GS), the Beck Depression Inventory, and
      the Recovery-Stress-Questionnaire for Work. Cluster analyses with the three MBI
      GS subscales as clustering variables were used to identify the burnout subtypes.
      Subsequent multivariate/univariate analysis of variance and Pearson chi-square
      tests were performed to investigate differences in depression, recovery/resources
      stress balance, and sociodemographic characteristics. RESULTS: Three different
      burnout subtypes were discovered: the exhausted subtype, the exhausted/cynical
      subtype, and the burned-out subtype. The burned-out subtype and the
      exhausted/cynical subtype showed both more severe depression symptoms and a worse
      recovery/resources-stress balance than the exhausted subtype. Furthermore, the
      burned-out subtype was more depressed than the exhausted/cynical subtype, but no
      difference was observed between these two subtypes with regard to perceived
      stress, recovery, and resources. Sociodemographic characteristics were not
      associated with the subtypes. CONCLUSIONS: The present study indicates that there
      are different subtypes in clinical burnout patients (exhausted,
      exhausted/cynical, and burned-out), which might represent patients at different
      developmental stages in the burnout cycle. Future studies need to replicate the
      current findings, investigate the stability of the symptom patterns, and examine
      the efficacy of rehabilitation interventions in different subtypes.

PMID- 29343239
TI  - Calcium-dependent protein kinases in cotton: insights into early plant responses
      to salt stress.
AB  - BACKGROUND: Soil salinization is one of the major environmental constraints to
      plant growth and agricultural production worldwide. Signaling components
      involving calcium (Ca2+) and the downstream calcium-dependent protein kinases
      (CPKs) play key roles in the perception and transduction of stress signals.
      However, the study of CPKs in cotton and their functions in response to salt
      stress remain unexplored. RESULTS: A total of 98 predicted CPKs were identified
      from upland cotton (Gossypium hirsutum L. 'TM-1'), and phylogenetic analyses
      classified them into four groups. Gene family distribution studies have revealed
      the substantial impacts of the genome duplication events to the total number of
      GhCPKs. Transcriptome analyses showed a wide distribution of CPKs' expression
      among different organs. A total of 19 CPKs were selected for their rapid
      responses to salt stress at the transcriptional level, most of which were also
      incduced by the thylene-releasing chemical ethephon, suggesting a partal overlap
      of the salinity and ethylene responses. Silencing of 4 of the 19 CPKs (GhCPK8,
      GhCPK38, GhCPK54, and GhCPK55) severely compromised the basal cotton resistance
      to salt stress. CONCLUSIONS: Our genome-wide expression analysis of CPK genes
      from up-land cotton suggests that CPKs are involved in multiple developmental
      responses as well as the response to different abiotic stresses. A cluster of the
      cotton CPKs was shown to participate in the early signaling events in cotton
      responses to salt stress. Our results provide significant insights on functional
      analysis of CPKs in cotton, especially in the context of cotton adaptions to salt
      stress.

PMID- 29343240
TI  - Attempted suicide of ethnic minority girls with a Caribbean and Cape Verdean
      background: rates and risk factors.
AB  - BACKGROUND: WHO data shows that female immigrants in Europe attempt suicide at
      higher rates than 'native' women and 'native' and immigrant men. Empirical
      studies addressing attempted suicide of female immigrants of Caribbean (Antillean
      Dutch and Creole-Surinamese-Dutch) as well as Cape Verdean descent in Europe are
      however scarce. We aim to increase knowledge about rates and risk factors of
      girls of Caribbean and Cape Verdean descent living in the Netherlands. METHODS:
      We conducted logistic regression on a dataset that consisted of self-reported
      health and well-being surveys filled out by 5611 female students, age 14-16, in
      Rotterdam, the Netherlands (Antillean Dutch N = 357, Creole-Surinamese-Dutch N =
      130, and Cape Verdean-Dutch N = 402, and Dutch 'natives' N = 4691). We studied if
      girls of these minority groups had elevated risk for attempted suicide. Risk
      indicators that were suspected to play a role were investigated i.e. household
      composition, socio-economic class, externalizing problems, emotional problems and
      sexual abuse. RESULTS: We found that rates of attempted suicide among Antillean
      (14%), Creole-Surinamese young women (15.4%) were higher than of 'native' Dutch
      girls (9.1%), while rates of Cape-Verdean girls (8.3%) were rather similar to
      those of 'native' girls. Not living with two biological parents was a risk factor
      for 'native' girls, but not for girls of Caribbean and Cape Verdean descent.
      Emotional problems and sexual abuse seems to be a risk indicator for suicidality
      across all ethnicities. Aggressive behaviour was a risk factor for Antillean
      Dutch and 'native' girls. CONCLUSIONS: Our findings underscore the need for
      developing suicide prevention programs for minority girls in multicultural cities
      in western Europe, in particular those of Caribbean descent. Results suggest the
      importance of addressing socio-economic class and educational background for
      suicide prevention, which bear particular relevance for Caribbean populations.
      Referral in the case of sexual trauma and low psychological wellbeing seems
      critical for reducing suicidal behaviour in girls, regardless of ethnicity.

PMID- 29343241
TI  - Clinical features and dysfunctions of iron metabolism in Parkinson disease
      patients with hyper echogenicity in substantia nigra: a cross-sectional study.
AB  - BACKGROUND: Transcranial ultrasound is a useful tool for providing the evidences
      for the early diagnosis and differential diagnosis of Parkinson disease (PD).
      However, the relationship between hyper echogenicity in substantia nigra (SN) and
      clinical symptoms of PD patients remains unknown, and the role of dysfunction of
      iron metabolism on the pathogenesis of SN hyper echogenicity is unclear. METHODS:
      PD patients was detected by transcranial sonography and divided into with no
      hyper echogenicity (PDSN-) group and with hyper echogenicity (PDSN+) group. Motor
      symptoms (MS) and non-motor symptoms (NMS) were evaluated, and the levels of iron
      and related proteins in serum and cerebrospinal fluid (CSF) were detected for PD
      patients. Data comparison between the two groups and correlation analyses were
      performed. RESULTS: PDSN+ group was significantly older, and had significantly
      older age of onset, more advanced Hohen-Yahr stage, higher SCOPA-AUT score and
      lower MoCA score than PDSN- group (P < 0.05). Compared with PDSN- group, the
      levels of transferrin and light-ferritin in serum and iron level in CSF were
      significantly elevated (P < 0.05), but ferroportin level in CSF was significantly
      decreased in PDSN+ group (P < 0.05). CONCLUSIONS: PD patients with hyper
      echogenicity in SN are older, at more advanced disease stage, have severer motor
      symptoms, and non-motor symptoms of cognitive impairment and autonomic
      dysfunction. Hyper echogenicity of SN in PD patients is related to dysfunction of
      iron metabolism, involving increased iron transport from peripheral system to
      central nervous system, reduction of intracellular iron release and excessive
      iron deposition in brain.

PMID- 29343242
TI  - Stage of cancer diagnoses among migrants from the former Soviet Union in
      comparison to the German population - are diagnoses among migrants delayed?
AB  - BACKGROUND: In this study, we compared stage at diagnosis, standardized incidence
      ratio (SIR) and standardized mortality ratio (SMR) of most frequent cancer
      diagnoses between re-settlers (Aussiedler) from the former Soviet Union and the
      general population in the Saarland in Germany to assess possible delays in
      diagnosis of cancer among this migrant group. METHODS: Lung cancer, colorectal
      cancer, breast cancer, prostate cancer, malignant melanoma of the skin and
      stomach cancer diagnoses among a cohort of 18,619 re-settlers living in the
      Saarland between 1990 and 2009 were identified by the federal state's cancer
      registry. Vital status was available for the respective time-period and used to
      calculate SIR and SMR in comparison to the autochthonous population. Tumor stages
      were condensed into local and advanced stages. Odds ratios (OR) for an advanced
      tumor stage were modeled in dependence of re-settler-status and relevant
      covariates by logistic regression. Missing values were addressed in a sensitivity
      analysis. The influence of duration of stay in Germany on advanced stage
      diagnosis was analyzed among re-settlers. RESULTS: SIR and SMR of lung and breast
      cancer were lower among female re-settlers, while SIR and SMR of colorectal and
      prostate cancer were lower among male re-settlers. SIR and SMR of stomach cancer
      were elevated among both sexes. Female re-settlers showed an elevated OR for
      being diagnosed with advanced stage breast cancer. Both male and female re
      settlers showed an elevated OR when observing all six sites combined (OR among
      males 1.47, p = 0.04; OR among females 1.37, p = 0.05). The result of elevated
      ORs was supported in the sensitivity analysis. Finally, male re-settlers showed a
      weak association between duration of stay in Germany and reduced risk for
      advanced stage diagnosis. CONCLUSION: Re-settlers were more likely to be
      diagnosed at an advanced tumor stage. These findings are in line with previous
      research having shown unfavorable health care utilization of re-settlers.
      Overall, low mortality rates despite an increased risk of advanced stage at
      diagnosis argue for a sufficient follow-up care, comparable to the autochthonous
      population.

PMID- 29343243
TI  - Retrospectively assessed psychosocial working conditions as predictors of
      prospectively assessed sickness absence and disability pension among older
      workers.
AB  - BACKGROUND: The aim was to explore the association between retrospectively
      assessed psychosocial working conditions during working life and prospectively
      assessed risk of sickness absence and disability pension among older workers.
      METHODS: The prospective risk of register-based long-term sickness absence (LTSA)
      and disability pension was estimated from exposure to 12 different psychosocial
      work characteristics during working life among 5076 older workers from the CAMB
      cohort (Copenhagen Aging and Midlife Biobank). Analyses were censored for
      competing events and adjusted for age, gender, physical work environment,
      lifestyle, education, and prior LTSA. RESULTS: LTSA was predicted by high levels
      of cognitive demands (HR 1.31 (95% CI 1.10-1.56)), high levels of emotional
      demands (HR 1.26 (95% CI 1.07-1.48)), low levels of influence at work (HR 1.30
      (95% CI 1.03-1.64)), and high levels of role conflicts (HR 1.34 (95% CI 1.09
      1.65)). Disability pension was predicted by low levels of influence at work (HR
      2.73 (95% CI 1.49-5.00)) and low levels of recognition from management (HR 2.04
      (95% CI 1.14-3.67)). CONCLUSIONS: This exploratory study found that
      retrospectively assessed high cognitive demands, high and medium emotional
      demands, low influence at work, low recognition from management, medium role
      clarity, and high role conflicts predicted LTSA and/or disability pension.

PMID- 29343244
TI  - Hsp70 at the membrane: driving protein translocation.
AB  - Efficient movement of proteins across membranes is required for cell health. The
      translocation process is particularly challenging when the channel in the
      membrane through which proteins must pass is narrow-such as those in the
      membranes of the endoplasmic reticulum and mitochondria. Hsp70 molecular
      chaperones play roles on both sides of these membranes, ensuring efficient
      translocation of proteins synthesized on cytosolic ribosomes into the interior of
      these organelles. The "import motor" in the mitochondrial matrix, which is
      essential for driving the movement of proteins across the mitochondrial inner
      membrane, is arguably the most complex Hsp70-based system in the cell.

PMID- 29343245
TI  - An unusual case of symptomatic deep vein thrombosis and pulmonary embolism after
      arthroscopic meniscus surgery.
AB  - BACKGROUND: Although thrombosis complication is rare after arthroscopic meniscus
      surgery, deep vein thrombosis and pulmonary embolism can be fatal. The associated
      risk factors and whether anticoagulant prevention after arthroscopic knee surgery
      is necessary have not reach consensus. Here we present a case of deep vein
      thrombosis and pulmonary embolism after a common arthroscopic meniscectomy. CASE
      PRESENTATION: The patient had no risk factors except ipsilateral leg varicose
      veins. She present swell at knee and calf from postoperative 3 weeks, and
      developed dyspnea, palpitation, and nausea on 33th day, pulmonary embolism was
      confirmed with CT angiography at emergency department. After thrombolysis and
      anticoagulation therapy were administered, the patient improved well and
      discharged. And the intravenous ultrasound confirmed thrombosis of popliteal vein
      and small saphenous vein. Who don't have common risk factors for venous
      thromboembolism. CONCLUSIONS: Despite the low incidence of thromboembolic
      complications after simple arthroscopy surgery, its life-threatening and
      devastating property make clinicians rethink the necessity of thromboprophylaxis
      and importance of preoperative relative risk factors screening.

PMID- 29343246
TI  - Influence of preoperative life satisfaction on recovery and outcomes after
      colorectal cancer surgery - a prospective pilot study.
AB  - BACKGROUND: Colorectal surgery has an important impact on a patient's quality of
      life, and postoperative rehabilitation shows large variations. To enhance the
      understanding of recovery after colorectal cancer, health-related quality of life
      has become a standard outcome measurement for clinical care and research.
      Therefore, we aimed to correlate the influence of preoperative global life
      satisfaction on subjective feelings of well-being with clinical outcomes after
      colorectal surgery. METHODS: In this pilot study of consecutive colorectal
      surgery patients, various dimensions of feelings of preoperative life
      satisfaction were assessed using a self-rated scale, which was validated in
      French. Both objective (length of stay and complications) and subjective (pain,
      subjective well-being and quality of sleep) indicators of recovery were evaluated
      daily during each patient's hospital stay. RESULTS: A total of 112 patients were
      included. The results showed a negative relationship between life satisfaction
      and postoperative complications and a significant negative correlation with the
      length of stay. Moreover, a significant positive correlation between life
      satisfaction and the combined subjective indicators of recovery was observed.
      CONCLUSION: We have shown the importance of positive preoperative mental states
      and global life satisfaction as characteristics that are associated with an
      improved recovery after colorectal surgery. Therefore, patients with a good level
      of life satisfaction may be better able to face the consequences of colorectal
      surgery, which is a relevant parameter in supportive cancer care.

PMID- 29343247
TI  - Consumption of sugar-sweetened beverages and artificially sweetened beverages
      from childhood to adulthood in relation to socioeconomic status - 15 years follow
      up in Norway.
AB  - BACKGROUND: In Norway, social inequalities in health and health-related behaviors
      have been reported despite the well-developed welfare state. The objective of the
      present study was to analyze; (i) the development in frequency of consumption of
      sugar-sweetened beverages (SSB) and artificially sweetened beverages (ASB) from
      childhood to adulthood; (ii) socioeconomic inequalities in the consumption of SSB
      and ASB using different indicators of socioeconomic status (SES); (iii) time
      trends in potential disparities in SSB and ASB consumption among different
      socioeconomic groups to assess the development in socioeconomic inequality from
      childhood to adulthood. METHODS: This study uses data from the Fruits and
      Vegetables Make the Marks (FVMM) longitudinal cohort, including participants (n =
      437) from 20 random schools from two Norwegian counties. Data from the first
      survey in 2001 (mean age 11.8) and follow-up surveys in 2005 (mean age 15.5) and
      2016 (mean age 26.5) were used. Consumption of SSB and ASB were measured using a
      food frequency questionnaire, which the participants completed at school in 2001
      and 2005, and online in 2016. Various indicators of SES were included; in 2001,
      parental education and income were measured, in 2005, participants' educational
      intentions in adolescence were measured, and in 2016, participants' own education
      and income were measured. The main analyses conducted were linear mixed effects
      analysis of the repeated measures. RESULTS: Between 2001 and 2016, a decrease in
      frequency of consumption of SSB (2.8 v 1.3 times/week; p = < 0.001) and an
      increase in frequency of consumption of ASB (1.1 v 1.6 times/week; p = 0.002)
      were observed. Participants with a higher educational level in adulthood and
      higher educational intentions in adolescence had a significantly lower frequency
      of consumption of SSB at all time points (2001, 2005 and 2016). No significant
      widening (or narrowing) of inequalities were observed from childhood to
      adulthood. CONCLUSIONS: A decrease in consumption of SSB and an increase in
      consumption of ASB from childhood to adulthood were found. Participants with high
      SES consumed in general less SSB (but not ASB), however, results varied depending
      on SES indicator used. The established inequalities persisted from childhood to
      adulthood.

PMID- 29343248
TI  - Minimally invasive versus open Transforaminal lumbar Interbody fusion in obese
      patients: a meta-analysis.
AB  - BACKGROUND: Minimally invasive transforaminal lumbar interbody fusion (MI-TLIF)
      has been employed in increasing cases compared with open TLIF (Open-TLIF).
      However, it is uncertain whether the advantages of MI-TLIF can also be
      specifically applied in obese patients. Therefore, the current study was thereby
      carried out aiming to compare the outcomes of MI-TLIF with those of Open-TLIF in
      obese patients with lumbar degenerative diseases. METHODS: Electronic databases
      were systemically retrieved from construction to May 2017. Meanwhile, the odds
      ratio (OR), mean difference (MD) and 95% confidence intervals (CI) were
      determined. RESULTS: A total of 7 observational cohort studies were enrolled into
      the current meta-analysis. The results indicated that, compared with Open-TLIF
      group, MI-TLIF could remarkably reduce the operative time (P = 0.002),
      intraoperative blood loss (P < 0.001), postoperative drainage (P = 0.01), length
      of stay (P < 0.001) and incidence of complications (P < 0.001). In addition, MI
      TLIF could also lead to markedly lower early back pain-Visual Analog Scale (BP
      VAS) score than that of Open-TLIF (P < 0.001), but no statistically significant
      differences were found in Oswestry Disability Index (ODI), late BP-VAS, early leg
      pain-VAS (LP-VAS) and late LP-VAS scores. CONCLUSION: MI-TLIF may be a more
      preferred choice for obese patients undergoing spinal surgery. However,
      differences in the long-term functional and pain outcomes between MI-TLIF and
      Open-TLIF remain a source of controversy, which should be further verified in
      future randomized-control trials.

PMID- 29343249
TI  - microRNA-124 inhibits bone metastasis of breast cancer by repressing Interleukin
      11.
AB  - BACKGROUND: Most patients with breast cancer in advanced stages of the disease
      suffer from bone metastases which lead to fractures and nerve compression
      syndromes. microRNA dysregulation is an important event in the metastases of
      breast cancer to bone. microRNA-124 (miR-124) has been proved to inhibit cancer
      progression, whereas its effect on bone metastases of breast cancer has not been
      reported. Therefore, this study aimed to investigate the role and underlying
      mechanism of miR-124 in bone metastases of breast cancer. METHODS: In situ
      hybridization (ISH) was used to detect the expression of miR-124 in breast cancer
      tissues and bone metastatic tissues. Ventricle injection model was constructed to
      explore the effect of miR-124 on bone metastasis in vivo. The function of cancer
      cell derived miR-124 in the differentiation of osteoclast progenitor cells was
      verified in vitro. Dual-luciferase reporter assay was conducted to confirm
      Interleukin-11 (IL-11) as a miR-124 target. The involvement of miR-124/IL-11 in
      the prognosis of breast cancer patients with bone metastasis was determined by
      Kaplan-Meier analysis. RESULTS: Herein, we found that miR-124 was significantly
      reduced in metastatic bone tissues from breast cancers. Down-regulation of miR
      124 was associated with aggressive clinical characteristics and shorter bone
      metastasis-free survival and overall survival. Restoration of miR-124 suppressed,
      while inhibition of miR-124 promoted the bone metastasis of breast cancer cells
      in vivo. At the cellular level, gain of function and loss-of function assays
      indicated that cancer cell-derived miR-124 inhibited the survival and
      differentiation of osteoclast progenitor cells. At the molecular level, we
      demonstrated that IL-11 partially mediated osteoclastogenesis suppression by miR
      124 using in vitro and in vivo assays. Furthermore, IL-11 levels were inversely
      correlated with miR-124, and up-regulation IL-11 in bone metastases was
      associated with a poor prognosis. CONCLUSIONS: Thus, the identification of a
      dysregulated miR-124/IL-11 axis helps elucidate mechanisms of breast cancer
      metastases to bone, uncovers new prognostic markers, and facilitates the
      development of novel therapeutic targets to treat and even prevent bone
      metastases of breast cancer.

PMID- 29343250
TI  - Evaluation of health status in patients with hepatitis c treated with and without
      interferon.
AB  - BACKGROUND: The evolution of technology in healthcare has increased the health
      care's costs and, the universal healthcare systems, in developed countries, need
      to ensure proper allocation of resources. Thus, the major issue is assessing the
      effectiveness of new medical technologies. The evaluation of quality of life in
      response to new treatments has become a key indicator in chronic conditions for
      which medical interventions are evaluated not only in terms of increasing the
      number of expected life years but also in terms of increasing quality of life.
      The aim of this observational study was to verify whether a simple instrument (EQ
      5D-5 L) can capture variations in health-related quality of life (HRQoL) and
      allow us to evaluate the impact of different drug treatment protocols in patients
      with hepatitis C virus (HCV) on daily activities. METHODS: Sixty six patients
      with HCV were consecutively enrolled in the Hepatology Unit at the University
      Hospital of Catania "G. Rodolico". Sixteen patients received new direct-acting
      antiviral agents (DAAs) plus pegylated alpha interferon (Peg-alpha-IFN) protocol
      (Group A) and 50 DAAs IFN free protocol (Group B). The EQ-5D-5 L(r) questionnaire
      and visual analog scale (VAS) were given to both groups to calculate
      coefficient's utility. We used the EQ-5D-5 L Crosswalk Index Value Calculator to
      obtain the utility EQIndex and both parametric and non parametric tests for the
      statistical analysis. RESULTS: The biopsy taken at the beginning of treatment
      showed comparable cell damage in both groups. The difference in the VAS results
      was negative for patients who received protocols containing IFN (indicating
      decreased quality of life),whereas it was positive in patients treated with IFN
      free protocols. The baseline EQIndex did not reveal any differences between the
      two treatment groups. The post-treatment EQIndex was statistically better in the
      groups that received IFN-free therapy. CONCLUSIONS: When innovative treatments
      are introduced into clinical practice, assessing quality of life is mandatory to
      determine their benefits. The instruments used in the present study are effective
      in detecting the areas in which improvement has occurred. These instruments can
      be easily managed by general practitioners for follow up of progression of the
      disease and referred to the specialist.

PMID- 29343251
TI  - Effects of the isoflavone genistein in early life stages of the Senegalese sole,
      Solea senegalensis: role of the Survivin and proliferation versus apoptosis
      pathways.
AB  - BACKGROUND: Phytochemical flavonoids are widely distributed in the environment
      and are derived from many anthropogenic activities. The isoflavone genistein is a
      naturally occurring compound found in soya products that are habitual
      constituents of the aquafeeds. This isoflavone possesses oestrogenic biological
      activity and also apoptotic properties. The present study has been performed to
      determine the effects of the genistein in the early life stages of the flatfish
      Senegalese sole during the first month of larval life, and it is focused
      especially at the metamorphosis, analysing the expression transcript levels and
      the immunohistochemical protein patterns implicated in the cell proliferation and
      apoptosis pathways (proliferation cellular/PCNA, anti-apoptosis Survivin/BIRC-5,
      death receptors/Fas, and Caspases). RESULTS: The isoflavone genistein induced
      some temporal disrupting effects in several pro-apoptotic signalling pathways
      (Fas, CASP-6) at both genistein doses (3 mg/L and 10 mg/L), with increased Fas
      transcripts and also decreasing CASP-6 mRNA expression levels during metamorphic
      and post-metamorphic stages of the Senegalese sole. On the other hand, the anti
      apoptotic BIRC-5 expression levels were weakly down-regulated with both the
      highest and lowest doses, but all of these imbalances were stabilised to the
      baseline levels. In early life stages of the controls, the constitutive basal
      transcript levels were temporarily and differentially expressed, reaching the
      highest levels at the pre-metamorphosis phase, as especially in endotrophic
      larvae (i.e. BIRC-5 mRNA), as well as in the metamorphic (i.e. CASP-6 mRNA) and
      post-metamorphic stages (i.e. Fas mRNA). In general, through development,
      continuous and progressive increases in the protein patterns of cell
      proliferation-PCNA (e.g. mitotic nuclei), anti-apoptotic Survivin (e.g.
      haematopoietic system, brain, digestive system, gills) and CASP-2 and -6 (e.g.
      brain, gills, kidney, digestive system, vascular systems, among others) have been
      immunohistochemically detected. Besides, both the controls and genistein exposed
      larvae displayed parallel immunostaining protein patterns in the different organ
      systems and tissues. CONCLUSIONS: The transcriptional imbalances observed in the
      studied genes (BIRC-5, CASP-6, Fas) were only temporarily induced, and apparently
      no changes in the immunohistochemical protein patterns were detected. Thus, the
      isoflavone genistein caused not harmful effects in the development and
      metamorphosis of the Senegalese sole exposed to chronic environmentally relevant
      concentrations (3 and 10 mg/L).

PMID- 29343252
TI  - Insights into the genetics of blood pressure in black South African individuals:
      the Birth to Twenty cohort.
AB  - BACKGROUND: Cardiovascular diseases (CVDs) are the leading cause of non
      communicable disease deaths globally, with hypertension being a major risk factor
      contributing to CVDs. Blood pressure is a heritable trait, with relatively few
      genetic studies having been performed in Africans. This study aimed to identify
      genetic variants associated with variance in systolic (SBP) and diastolic (DBP)
      blood pressure in black South Africans. METHODS: Genotyping was performed using
      the Metabochip in a subset of participants (mixed sex; median age 17.9) and their
      adult female caregivers (median age 41.0) from the Birth to Twenty cohort (n =
      1947). Data were analysed as a merged dataset (all participants and caregivers
      together) in GEMMA (v0.94.1) using univariate linear mixed models, incorporating
      a centered relatedness matrix to account for the relatedness between individuals
      and with adjustments for age, sex, BMI and principal components of the genotype
      information. RESULTS: Association analysis identified regions of interest in the
      NOS1AP (DBP: rs112468105 - p = 7.18 * 10-5 and SBP: rs4657181 - p = 4.04 * 10-5),
      MYRF (SBP: rs11230796 - p = 2.16 * 10-7, rs400075 - p = 2.88 * 10-7) and POC1B
      (SBP: rs770373 - p = 7.05 * 10-5, rs770374 - p = 9.05 * 10-5) genes and some
      intergenic regions (DACH1|LOC440145 (DBP: rs17240498 - p = 4.91 * 10-6 and SBP:
      rs17240498 - p = 2.10 * 10-5) and INTS10|LPL (SBP: rs55830938 - p = 1.30 * 10-5,
      rs73599609 - p = 5.78 * 10-5, rs73667448 - p = 6.86 * 10-5)). CONCLUSIONS: The
      study provided further insight into the contribution of genetic variants to blood
      pressure in black South Africans. Future functional and replication studies in
      larger samples are required to confirm the role of the identified loci in blood
      pressure regulation and whether or not these variants are African-specific.

PMID- 29343253
TI  - An integrated primary care approach for frail community-dwelling older persons: a
      step forward in improving the quality of care.
AB  - BACKGROUND: High-quality care delivery for frail older persons, many of whom have
      multiple complex needs, is among the greatest challenges faced by healthcare
      systems today. The Chronic Care Model (CCM) may guide quality improvement efforts
      for primary care delivery to frail older populations. Objectives of this study
      were to assess the implementation of interventions in CCM dimensions, and to
      investigate the quality of primary care as perceived by healthcare professionals,
      in practices following the Finding and Follow-up of Frail older persons (FFF)
      integrated care approach and those providing usual care. METHODS: Structured
      interviews were conducted with general practitioners (GPs) from 11 intervention
      practices and 4 control practices to assess the implementation of interventions.
      A longitudinal survey (12-month period, 2 measurement timepoints) was conducted
      to assess the quality of primary care as perceived by healthcare professionals
      (intervention and control GP practices) using the Assessment of Chronic Illness
      Care Short version (ACIC-S). Independent-samples t-tests were used to assess
      differences in ACIC-S scores between groups. Interviews were conducted with GPs
      from the intervention practices to gain a deeper understanding of their
      experiences with the FFF approach. RESULTS: Intervention practices implemented
      significantly more interventions congruent with (dimensions of) the CCM compared
      with control GP practices. With respect to the quality of primary care as
      perceived by healthcare professionals, mean ACIC-S scores for all CCM dimensions
      and overall mean ACIC-S scores were significantly higher in the intervention
      group than in the control group at the follow-up timepoint. The number of
      implemented interventions was associated positively with perceived quality of
      primary care (ACIC-S scores) at follow-up. Important motives of GPs to implement
      the FFF approach were the aging of the population and transformations in the
      primary care sector. Proactive care delivery and multidisciplinary collaboration
      were considered to be essential. Major challenges to the implementation and
      embedding of the FFF approach were structural financing and manpower, and the
      availability of a facilitating information and communication technology system.
      CONCLUSIONS: Our study showed that proactive, integrated care that is based on
      (elements of) the CCM may be a step forward in improving quality of care for
      frail older persons.

PMID- 29343254
TI  - Knowledge of cervical cancer and Pap smear among Uyghur women from Xinjiang,
      China.
AB  - BACKGROUND: Cervical cancer is a significant public health issue in Xinjiang
      China. In order to provide scientific basis for cervical cancer intervention in
      Xinjiang, women's knowledge of cervical cancer was investigated in this study.
      Besides, relations between Uyghur women's awareness and their age, educational
      background, yearly household were evaluated. METHODS: Questionnaire survey was
      conducted to 7100 Uyghur women from Karkax Hotan and Payzivat Kashgar during 2008
      and 2009. Women aged 21 to 70 years, had sexual activity, no history of cervical
      lesion or cervical cancer were considered to be eligible to the study.
      Information include participants' socio-demographic background, personal data,
      awareness about Pap smear, about cervical cancer and HPV, sources of information
      acquisition was investigated. RESULTS: 65.1% of the 7100 respondents with primary
      education level, and 95.0% participants were farmers. Only 7.4% had undertaken
      Pap smears before, not aware of the importance of the test (97.4% of 7100) was
      the main reason for not performing Pap smears. 29.3% of total participants had
      heard about cervical cancer, and only 0.14% (10 out of 7100) had heard about HPV.
      Top three route of knowledge acquire were television advertises (39.1%),
      neighbors (21.0%) and health care providers (15.0%). Women younger than 40 years,
      with higher educational levels and higher income had better awareness of cervical
      cancer and more willing to accept regular Pap smears. CONCLUSIONS: Uyghur women
      in Xinjiang had poor knowledge of cervical cancer and HPV infection. Low
      awareness of women was associated with less household income and lower
      educational levels. TV shows and education from health care providers may
      increase women's participation in cervical cancer control and prevention.

PMID- 29343255
TI  - Inducible HIV RNA transcription assays to measure HIV persistence: pros and cons
      of a compromise.
AB  - With the increasing number of therapeutic strategies tested in humans to reduce
      the size of the latent reservoir, the development of a robust, precise and
      clinical trial scalable assay that measures the frequency of infected cells
      carrying inducible replication-competent HIV is urgently needed. The size of the
      pool of cells carrying replication-competent HIV is largely overestimated by DNA
      assays, as a result of a large proportion of defective viruses, and
      underestimated by co-culture outgrowth assays. New culture methods that measure
      the inducible HIV reservoir have been developed during the past few years. In
      these induction assays, CD4+ T cells from virally suppressed individuals are
      activated and HIV RNA is measured in cell extracts or cell supernatants. In this
      review, we summarize the principle and outcomes of these assays and discuss the
      potential of these methods in the evaluation of HIV eradication strategies.

PMID- 29343256
TI  - The effects of green cardamom supplementation on blood glucose, lipids profile,
      oxidative stress, sirtuin-1 and irisin in type 2 diabetic patients: a study
      protocol for a randomized placebo-controlled clinical trial.
AB  - BACKGROUND: It has been suggested that the antioxidant, anti-inflammatory and
      hypolipidemic activities of cardamom may improve diabetes. However, the effect of
      this spice has not been investigated in diabetic subjects. This study was planned
      to determine the effects of green cardamom on blood glucose, lipids and oxidative
      stress status in type 2 diabetic patients. METHODS/DESIGN: Eighty overweight or
      obese patients with type 2 diabetes will be selected. They will be randomly
      assigned to receive 3 g/d green cardamom or placebo for 10 weeks. The socio
      demographic, physical activity and 24-h food recall questionnaires will be
      collected for each subject. Weight, height and waist circumference will be
      measured. Determination of blood glucose, lipid profile, and oxidative stress
      biomarkers including serum levels of total antioxidant capacity (TAC),
      malondialdehyde (MDA), and glutathione peroxidase (GPx) and superoxide dismutase
      (SOD) in red blood cells will be performed. The homeostasis model assessment
      estimated insulin resistance (HOMA-IR) index and the quantitative insulin
      sensitivity check index (QUICKI) will be calculated. Also, serum levels of
      irisin, and Sirtuin1 (SIRT1) will be measured. DISCUSSION: This trial will be the
      first study to explore the effects of green cardamom supplementation on glycemic
      control, lipid profile and oxidative stress in patients with type 2 diabetes
      mellitus. The results from this trial will provide evidence on the efficacy of
      green cardamom in type 2 diabetes mellitus. TRIAL REGISTRATION NUMBER: (
      http://www.irct.ir , identifier: IRCT2016042717254N5), Registration date:
      23.11.2016.

PMID- 29343257
TI  - Pigmented villonodular synovitis in pediatric population: review of literature
      and a case report.
AB  - BACKGROUND: Pigmented villonodular synovitis (PVNS) is a rare proliferative
      process in children that mostly affects the knee joint. CASE PRESENTATION: The
      study follows the case of a 3-year-old boy presenting recurrent patellar
      dislocation and PVNS. Due to symptoms such as chronic arthritis, he had been
      taking prednisolone and methotrexate for 6 months before receiving a definitive
      diagnosis. After a period of showing no improvements from his treatment, he was
      referred to our center and was diagnosed with local PVNS using magnetic resonance
      imaging (MRI). The patient was treated for his patellar dislocation by way of
      open synovectomy, lateral retinacular release, and a proximal realignment
      procedure, with no recurrence after a 24-month follow-up. CONCLUSION: PVNS may
      appear with symptoms resembling juvenile idiopathic arthritis, thus the disease
      should be considered in differential diagnosis of any inflammatory arthritis in
      children. PVNS may also cause mechanical symptoms such as patellar dislocation.
      In addition to synovectomy, a realignment procedure can be a useful method of
      treatment.

PMID- 29343258
TI  - Mass-spectrometric profiling of cerebrospinal fluid reveals metabolite biomarkers
      for CNS involvement in varicella zoster virus reactivation.
AB  - BACKGROUND: Varicella zoster virus (VZV) reactivation spans the spectrum from
      uncomplicated segmental herpes zoster to life-threatening disseminated CNS
      infection. Moreover, in the absence of a small animal model for this human
      pathogen, studies of pathogenesis at the organismal level depend on analysis of
      human biosamples. Changes in cerebrospinal fluid (CSF) metabolites may reflect
      critical aspects of host responses and end-organ damage in neuroinfection and
      neuroinflammation. We therefore applied a targeted metabolomics screen of CSF to
      three clinically distinct forms of VZV reactivation and infectious and non
      infectious disease controls in order to identify biomarkers for CNS involvement
      in VZV reactivation. METHODS: Metabolite profiles were determined by targeted
      liquid chromatography-mass spectrometry in CSF from patients with segmental
      zoster (shingles, n = 14), facial nerve zoster (n = 16), VZV
      meningitis/encephalitis (n = 15), enteroviral meningitis (n = 10), idiopathic
      Bell's palsy (n = 11), and normal pressure hydrocephalus (n = 15). RESULTS:
      Concentrations of 88 metabolites passing quality assessment clearly separated the
      three VZV reactivation forms from each other and from the non-infected samples.
      Internal cross-validation identified four metabolites (SM C16:1, glycine, lysoPC
      a C26:1, PC ae C34:0) that were particularly associated with VZV
      meningoencephalitis. SM(OH) C14:1 accurately distinguished facial nerve zoster
      from Bell's palsy. Random forest construction revealed even more accurate
      classifiers (signatures comprising 2-4 metabolites) for most comparisons. Some of
      the most accurate biomarkers correlated only weakly with CSF leukocyte count,
      indicating that they do not merely reflect recruitment of inflammatory cells but,
      rather, specific pathophysiological mechanisms. Across all samples, only the sum
      of hexoses and the amino acids arginine, serine, and tryptophan correlated
      negatively with leukocyte count. Increased expression of the metabolites
      associated with VZV meningoencephalitis could be linked to processes relating to
      neuroinflammation/immune activation, neuronal signaling, and cell stress,
      turnover, and death (e.g., autophagy and apoptosis), suggesting that these
      metabolites might sense processes relating to end-organ damage. CONCLUSIONS: The
      results provide proof-of-concept for the value of CSF metabolites as (1) disease
      associated signatures suggesting pathophysiological mechanisms, (2) degree and
      nature of neuroinflammation, and (3) biomarkers for diagnosis and risk
      stratification of VZV reactivation and, likely, neuroinfections due to other
      pathogens. TRIAL REGISTRATION: Not applicable (non-interventional study).

PMID- 29343259
TI  - Influence of apocynin on cardiac remodeling in rats with streptozotocin-induced
      diabetes mellitus.
AB  - BACKGROUND: Increased reactive oxygen species (ROS) generation in diabetes
      mellitus (DM) is an important mechanism leading to diabetic cardiomyopathy.
      Apocynin, a drug isolated from the herb Picrorhiza kurroa, is considered an
      antioxidant agent by inhibiting NADPH oxidase activity and improving ROS
      scavenging. This study analyzed the influence of apocynin on cardiac remodeling
      in diabetic rats. METHODS: Six-month-old male Wistar rats were assigned into 4
      groups: control (CTL, n = 15), control + apocynin (CTL + APO, n = 20), diabetes
      (DM, n = 20), and diabetes + apocynin (DM + APO, n = 20). DM was induced by
      streptozotocin. Seven days later, apocynin (16 mg/kg/day) or vehicle was
      initiated and maintained for 8 weeks. Left ventricular (LV) histological sections
      were used to analyze interstitial collagen fraction. NADPH oxidase activity was
      evaluated in LV samples. Comparisons between groups were performed by ANOVA for a
      2 * 2 factorial design followed by the Bonferroni post hoc test. RESULTS: Body
      weight (BW) was lower and glycemia higher in diabetic animals. Echocardiogram
      showed increased left atrial diameter, LV diastolic diameter, and LV mass indexed
      by BW in both diabetic groups; apocynin did not affect these indices. LV systolic
      function was impaired in DM groups and unchanged by apocynin. Isovolumic
      relaxation time was increased in DM groups; transmitral E/A ratio was higher in
      DM + APO compared to DM. Myocardial functional evaluation through papillary
      muscle preparations showed impaired contractile and relaxation function in both
      DM groups at baseline conditions. After positive inotropic stimulation, developed
      tension (DT) was lower in DM than CTL. In DM + APO, DT had values between those
      in DM and CTL + APO and did not significantly differ from either group.
      Myocardial interstitial collagen fraction was higher in DM than CTL and did not
      differ between DM + APO and CTL + APO. Serum activity of antioxidant enzymes
      glutathione peroxidase, superoxide dismutase (SOD), and catalase was lower in DM
      than CTL; apocynin restored catalase and SOD levels in DM + APO. Myocardial NADPH
      oxidase activity did not differ between groups. CONCLUSION: Apocynin restores
      serum antioxidant enzyme activity despite unchanged myocardial NADPH oxidase
      activity in diabetic rats.

PMID- 29343261
TI  - Prenatal exposure to perfluoroalkyl and polyfluoroalkyl substances and childhood
      atopic dermatitis: a prospective birth cohort study.
AB  - BACKGROUND: Perfluoroalkyl and polyfluoroalkyl substances (PFASs) have been
      reported to suppress immune function. However, previous studies on prenatal
      exposure to PFASs and allergic disorders in offspring provided inconsistent
      results. We aimed to examine the association between prenatal exposure to PFASs
      and childhood atopic dermatitis (AD) in offspring up to 24 months of age.
      METHODS: A prospective birth cohort study involving 1056 pregnant women was
      conducted in two hospitals in Shanghai from 2012 to 2015. Prenatal information
      was collected by an interview with the women and from medical records. Fetal
      umbilical cord blood was collected at birth. Cord blood plasma PFASs were
      measured. Children were followed at 6, 12 and 24 months and information on the
      development of AD was recorded. AD was diagnosed by 2 dermatologists
      independently based on the questionnaires. Multiple logistic regression was used
      to compute odds ratio (OR) and corresponding 95% confidence interval (CI) for the
      association between AD and each PFASs, adjusting for potential confounders.
      RESULTS: A total of 687 children completed a 2-year follow-up visit and had PFASs
      measurement. AD was diagnosed in 173 (25.2%) children during the first 24 months.
      In female children, a log-unit increase in perfluorooctanoic acid (PFOA) was
      associated with a 2.1-fold increase in AD risk (AOR 2.07, 95% CI 1.13-3.80) after
      adjusting for potential confounders. The corresponding risk was 2.22 (1.07-4.58)
      for perfluorononanoic acid (PFNA). The highest PFOA quartile was significantly
      associated with AD (2.52, 1.12-5.68) compared with the lowest quartile. The
      highest quartile of PFNA, perfluorodecanoic acid (PFDA) and perfluorohexane
      sulfonic acid (PFHxS) were associated with AD with AOR (95% CI) being 2.14 (0.97
      4.74), 2.14 (1.00-4.57), and 2.30 (1.03-5.15), respectively. Additionally, the
      second quartile of perfluorododecanoic acid (PFDoA) was associated with a 3.2
      fold increase in AD risk (3.24, 1.44-7.27). However, no significant associations
      were found in male children. CONCLUSIONS: Prenatal exposure to PFOA, PFDA, PFDoA
      and PFHxS significantly increased the risk of childhood AD in female children
      during the first 24 months of life. In addition, the associations between AD with
      prenatal exposure to PFNA were close to statistical significance.

PMID- 29343260
TI  - Liquid biomarkers in melanoma: detection and discovery.
AB  - A vast array of tumor-derived genetic, proteomic and cellular components are
      constantly released into the circulation of cancer patients. These molecules
      including circulating tumor DNA and RNA, proteins, tumor and immune cells are
      emerging as convenient and accurate liquid biomarkers of cancer. Circulating
      cancer biomarkers provide invaluable information on cancer detection and
      diagnosis, prognosticate patient outcomes, and predict treatment response. In
      this era of effective molecular targeted treatments and immunotherapies, there is
      now an urgent need to implement use of these circulating biomarkers in the clinic
      to facilitate personalized therapy. In this review, we present recent findings in
      circulating melanoma biomarkers, examine the challenges and promise of evolving
      technologies used for liquid biomarker discovery, and discuss future directions
      and perspectives in melanoma biomarker research.

PMID- 29343262
TI  - What motivates medical students to select medical studies: a systematic
      literature review.
AB  - BACKGROUND: There is a significant shortage of health workers across and within
      countries. It is of utmost importance to determine the factors that motivate
      students to opt for medical studies. The objective of this study is to group and
      review all the studies that investigated the motivational factors that underpin
      students' selection of medical study in recent years. METHODS: The literature
      search was carried out by two researchers independently in PubMed, Google
      Scholar, Wiley and IndMED databases for articles published from year 2006 till
      2016. A total of 38 combinations of MeSH words were used for search purpose.
      Studies related to medical students and interns have been included. The
      application of inclusion and exclusion criteria and PRISMA guidelines for
      reporting systematic review led to the final selection of 24 articles. RESULTS:
      The majority of the studies (n = 16; 66.6%) were from high-income countries
      followed by an equal number from upper-middle and lower-middle income countries
      (n = 4,16.7%). None of the studies were from low-income countries. All of the
      studies were cross-sectional in nature. The main motivating factors that emerged
      were scientific (interest in science / medicine, social interest and academia,
      flexible work hours and work independence), societal (prestige, job security,
      financial security) and humanitarian (serving the poor and under priviledged) in
      high-, upper-middle and lower-middle income countries, respectively. The findings
      were comparable to Maslow's hierarchy of needs theory of motivation. CONCLUSION:
      This systematic review identifies the motivational factors influencing students
      to join medical studies in different parts of the globe. These factors vary per
      country depending on the level of income. This study offers cues to policy makers
      and educators to formulate policy in order to tackle the shortage of health
      workers, i.e. medical doctors. However, more research is needed to translate
      health policy into concrete and effective measures.

PMID- 29343263
TI  - Knowledge, use, and disuse of unconventional food plants.
AB  - BACKGROUND: People's diets are usually restricted to a small number of plant
      species, even in regions with great diversity. We investigated the knowledge of
      residents in Ribeirao da Ilha, a district of Florianopolis (Santa Catarina,
      Brazil), about unconventional food plants (UFP). We report the UFP of the region,
      the parts used, the methods of processing, and the reasons for reduced use or
      even lack of use. METHODS: From June 2014 to January 2015, we interviewed 26 long
      established residents and made free listings of plant resources in the region. We
      also did three guided tours, and 24 residents (among the 26) checked pictures of
      the mentioned plants in order to identify them. RESULTS: We identified 63 species
      distributed in 25 botanical families. Half of the species were mentioned only by
      one informant. The fruit was the most frequently used part (80% of citations),
      consumed mainly without processing. Among those species, 27% were used
      exclusively in the past. The residents attributed non-use to the difficulty in
      locating the plants and loss of interest in the resource. CONCLUSION:
      Urbanization and environmental restrictions contribute to the difficulty of
      access to UFP. Encouraging residents to continue using UFP is necessary to
      perpetuate this threatened knowledge, promote a more diversified and healthier
      diet, stimulate a greater interaction among people and nature, and promote on
      farm conservation of edible plants.

PMID- 29343265
TI  - RNase If -treated quantitative PCR for dsRNA quantitation of RNAi trait in
      genetically modified crops.
AB  - BACKGROUND: RNA interference (RNAi) technology has been widely used to knockdown
      target genes via post-transcriptional silencing. In plants, RNAi is used as an
      effective tool with diverse applications being developed such as resistance
      against insects, fungi, viruses, and metabolism manipulation. To develop
      genetically modified (GM) RNAi traits for insect control, a transgene is created
      and composed of an inversely-repeated sequence of the target gene with a spacer
      region inserted between the repeats. The transgene design is subject to form a
      self-complementary hairpin RNA (hpRNA) and the active molecules are > 60 bp
      doubled-stranded RNA (dsRNA) derived from the hpRNA. However, in some cases, an
      undesirable intermediate such as single-stranded RNA (ssRNA) may be formed, which
      is not an active molecule. The aforementioned characteristics of RNAi traits lead
      to increase the challenges for RNAi-derived dsRNA quantitation. RESULTS: To
      quantify the dsRNA and distinguish it from the ssRNA in transgenic maize, an
      analytical tool is required to be able to effectively quantify dsRNA which
      contains a strong secondary structure. Herein, we develop a modified qRT-PCR
      method (abbreviated as RNase If -qPCR) coupled with a ssRNA preferred
      endonuclease (i.e., RNase If). This method enables the precise measurement of the
      active molecules (i.e., dsRNA) derived from RNAi traits of GM crops and
      separately quantifies the dsRNA from ssRNA. Notably, we also demonstrate that the
      RNase If -qPCR is comparable to a hybridization-based method (Quantigene Plex
      2.0). CONCLUSIONS: To our best knowledge, this is the first report of a method
      combining RNase If with modified qRT-PCR protocol. The method represents a
      reliable analytical tool to quantify dsRNA for GM RNAi crops. It provides a cost
      effective and feasible analytical tool for general molecular laboratory without
      using additional equipment for other methods. The RNase If -qPCR method
      demonstrates high sensitivity (to 0.001 pg/ MUL of dsRNA), precision and
      accuracy. In this report, we demonstrated the deployment of this method to
      characterize the RNAi events carrying v-ATPase C in maize during trait
      development process. The method can be utilized in any application which requires
      the dsRNA quantification such as double-stranded RNA virus or sprayable dsRNA as
      herbicide.

PMID- 29343264
TI  - Associations between circulating adipokines and bone mineral density in patients
      with knee osteoarthritis: a cross-sectional study.
AB  - BACKGROUND: Associations between adipokines and bone mineral density (BMD) in
      knee osteoarthritis (OA) remain indistinct. The aim of this study was to
      investigate the cross-sectional associations between serum levels of adipokines
      and BMD in patients with knee OA. METHODS: This study included 164 patients with
      symptomatic knee OA from the Anhui Osteoarthritis study. Serum levels of leptin,
      adiponectin, and resistin were measured using an enzyme-linked immunosorbent
      assay (ELISA). BMD at total body, spine, hip, and femur were measured by dual
      energy X-ray absorptiometry (DXA). RESULTS: In multivariable analyses, serum
      levels of leptin were significantly associated with reduced BMD at total body,
      hip, total femur, femoral neck, and femoral shaft (beta = - 0.019, 95% CI -0.034
      to - 0.005; beta = - 0.018, 95% CI -0.034 to - 0.003; beta = - 0.018, 95% CI 
      0.034 to - 0.002; beta = - 0.016, 95% CI -0.032 to 0.000; beta = - 0.026, 95% CI 
      0.046 to - 0.006; respectively). Serum levels of adiponectin were significantly
      and negatively associated with BMD at total femur and femoral shaft (beta = -
      0.007, 95% CI -0.013 to 0.000; beta = - 0.011, 95% CI -0.018 to - 0.003;
      respectively). However, no significant associations were found between serum
      levels of resistin and BMD at any site measured. CONCLUSIONS: Serum levels of
      leptin and adiponectin were significantly and negatively associated with BMD,
      suggesting potentially detrimental effects of leptin and adiponectin on BMD in
      knee OA patients.

PMID- 29343266
TI  - Identification of pain categories associated with change in pain in patients
      receiving placebo: data from two phase 3 randomized clinical trials in
      symptomatic knee osteoarthritis.
AB  - BACKGROUND: Pain is the principal clinical symptom of osteoarthritis (OA), and
      development of safe and effective analgesics for OA pain is needed. Drug
      development of new analgesics for OA pain is impaired by substantial change in
      pain in patients receiving placebo, and more data describing clinical
      characteristics and pain categories particularly associated with this phenomenon
      is needed. The purpose of this post-hoc analysis was to investigate clinical
      characteristics and pain categories and their association with radiographic
      progression and placebo pain reduction (PPR) in OA patients as measured the
      Western Ontario and McMasters Arthritis (WOMAC). METHODS: Pooled data from the
      placebo groups of two phase III randomized clinical trials in patients with knee
      OA followed for 2 years were analyzed. Differences between individual sub-scores
      and pain categories of weight-bearing and non-weight bearing pain over time were
      assessed. Selected patient baseline characteristics were assessed for association
      with PPR. Association between pain categories and radiographic progression was
      analyzed. RESULTS: The reduction of pain in placebo-treated patients was
      significantly higher in the composite of questions related to weight-bearing pain
      compared to non-weight-bearing pain of the target knee. Baseline BMI, age and JSW
      were not associated with pain change. Pain reduction was higher in the Target
      knee, compared to the Non-Target knee at all corresponding time-points. A very
      weak correlation was found between weight-bearing pain and progression in the non
      target knee. CONCLUSIONS: These results indicate that the reduction in pain in
      patients treated with placebo is significantly different between pain categories,
      as weight-bearing pain was significantly more reduced compared to non-weight
      bearing pain. Further research in pain categories in OA is warranted. TRIAL
      REGISTRATION: NCT00486434 (trial 1) and NCT00704847 (trial 2).

PMID- 29343267
TI  - TIPE2 suppresses progression and tumorigenesis of esophageal carcinoma via
      inhibition of the Wnt/beta-catenin pathway.
AB  - BACKGROUND: Esophageal carcinoma is the eighth prevalent malignancy and ranks the
      sixth in carcinoma-related death worldwide. Tumor necrosis factor-alpha-induced
      protein-8 like-2 (TIPE2) has been identified as a tumor suppressor in multiple
      carcinomas. However, its roles and molecular mechanisms underlying esophageal
      carcinoma progression are still undefined till now. METHODS: RT-qPCR assay was
      employed to detect the expression of TIPE2 mRNA. TIPE2 protein expression was
      measured by using western blot assay. Ad-V and Ad-TIPE2 adenoviruses were
      constructed to overexpress TIPE2. The effects of TIPE2 overexpression on cell
      proliferation, invasion and apoptosis were assessed by MTT and Edu incorporation
      assays, transwell invasion assay and flow cytometry analysis, respectively. The
      effect of TIPE2 overexpression on xenograft tumor growth was determined by
      measuring tumor volume and weight, together with immunohistochemistry assay. The
      effect of TIPE2 overexpression on the Wnt/beta-catenin signaling pathway was
      evaluated by detecting the protein levels of beta-catenin, c-Myc and cyclinD1 in
      EC9076 cells and xenograft tumors of esophageal carcinoma. RESULTS: TIPE2
      expression was downregulated in esophageal carcinoma tissues and cells.
      Adenovirus-mediated TIPE2 overexpression suppressed cell proliferation and
      invasion, and induced apoptosis in esophageal carcinoma cells. Enforced
      expression of TIPE2 inhibited tumor growth in vivo, as evidenced by the reduced
      tumor volume, tumor weight and proliferating cell nuclear antigen expression.
      Overexpression of TIPE2 inhibited the Wnt/beta-catenin signaling pathway in
      esophageal carcinoma in vitro and in vivo. CONCLUSIONS: These results suggest
      that TIPE2 suppressed progression and tumorigenesis of esophageal carcinoma via
      inhibition of the Wnt/beta-catenin pathway.

PMID- 29343268
TI  - Time-homogeneous Markov process for HIV/AIDS progression under a combination
      treatment therapy: cohort study, South Africa.
AB  - BACKGROUND: As HIV enters the human body, its main target is the CD4 cell which
      it turns into a factory that produces millions of other HIV particles. These HIV
      particles target new CD4 cells resulting in the progression of HIV infection to
      AIDS. A continuous depletion of CD4 cells results in opportunistic infections,
      for example tuberculosis (TB). The purpose of this study is to model and describe
      the progression of HIV/AIDS disease in an individual on antiretroviral therapy
      (ART) follow up using a continuous time homogeneous Markov process. A cohort of
      319 HIV infected patients on ART follow up at a Wellness Clinic in Bela Bela,
      South Africa is used in this study. Though Markov models based on CD4 cell counts
      is a common approach in HIV/AIDS modelling, this paper is unique clinically in
      that tuberculosis (TB) co-infection is included as a covariate. METHODS: The
      method partitions the HIV infection period into five CD4-cell count intervals
      followed by the end points; death, and withdrawal from study. The effectiveness
      of treatment is analysed by comparing the forward transitions with the backward
      transitions. The effects of reaction to treatment, TB co-infection, gender and
      age on the transition rates are also examined. The developed models give very
      good fit to the data. RESULTS: The results show that the strongest predictor of
      transition from a state of CD4 cell count greater than 750 to a state of CD4
      between 500 and 750 is a negative reaction to drug therapy. Development of TB
      during the course of treatment is the greatest predictor of transitions to states
      of lower CD4 cell count. Transitions from good states to bad states are higher on
      male patients than their female counterparts. Patients in the cohort spend a
      greater proportion of their total follow-up time in higher CD4 states.
      CONCLUSION: From some of these findings we conclude that there is need to monitor
      adverse reaction to drugs more frequently, screen HIV/AIDS patients for any signs
      and symptoms of TB and check for factors that may explain gender differences
      further.

PMID- 29343269
TI  - Microglial activation mediates chronic mild stress-induced depressive- and
      anxiety-like behavior in adult rats.
AB  - BACKGROUND: Depression is a heterogeneous disorder, with the exact neuronal
      mechanisms causing the disease yet to be discovered. Recent work suggests it is
      accompanied by neuro-inflammation, characterized, in particular, by microglial
      activation. However, microglial activation and its involvement in neuro
      inflammation and stress-related depressive disorders are far from understood.
      METHODS: We utilized multiple detection methods to detect the neuro-inflammation
      in the hippocampus of rats after exposure to chronic mild stress (CMS). Male
      Sprague Dawley (SD) rats were subjected to chronic mild stressors for 12 weeks.
      Microglial activation and hippocampal neuro-inflammation were detected by using a
      combinatory approach of in vivo [18F] DPA-714 positron emission computed
      tomography (PET) imaging, ionized calcium-binding adapter molecule 1 and
      translocator protein (TSPO) immunohistochemistry, and detection of NOD-like
      receptor protein 3 (NLRP3) inflammasome and some inflammatory mediators. Then,
      the rats were treated with minocycline during the last 4 weeks to observe its
      effect on hippocampal neuro-inflammation and depressive-like behavior induced by
      chronic mild stress. RESULTS: The results show that 12 weeks of chronic mild
      stress induced remarkable depressive- and anxiety-like behavior, simultaneously
      causing hippocampal microglial activation detected by PET, immunofluorescence
      staining, and western blotting. Likewise, activation of NLRP3 inflammasome and
      upregulation of inflammatory mediators, such as interleukin-1beta (IL-1beta), IL
      6, and IL-18, were also observed in the hippocampus after exposure to chronic
      stress. Interestingly, the anti-inflammatory mediators, such as IL-4 and IL-10,
      were also increased in the hippocampus following chronic mild stress, which may
      hint that chronic stress activates different types of microglia, which produce
      pro-inflammatory cytokines or anti-inflammatory cytokines. Furthermore, chronic
      minocycline treatment alleviated the depressive-like behavior induced by chronic
      stress and significantly inhibited microglial activation. Similarly, the
      activation of NLRP3 inflammasome and the increase of inflammatory mediators were
      not exhibited or significantly less marked in the minocycline treatment group.
      CONCLUSION: These results together indicate that microglial activation mediates
      the chronic mild stress-induced depressive- and anxiety-like behavior and
      hippocampal neuro-inflammation.

PMID- 29343271
TI  - p66Shc gene expression in peripheral blood mononuclear cells and progression of
      diabetic complications.
AB  - BACKGROUND: The risk of diabetic complications is modified by genetic and
      epigenetic factors. p66Shc drives the hyperglycaemic cell damage and its deletion
      prevents experimental diabetic complications. We herein tested whether p66Shc
      expression in peripheral blood mononuclear cells (PBMCs) predicts adverse
      outcomes in people with diabetes. METHODS: In a cohort of 100 patients with
      diabetes (16 type 1 and 84 type 2), we quantified baseline p66Shc expression in
      PBMCs by quantitative PCR. Patients were extensively characterized for
      demographics, anthropometrics, biochemical data, prevalence of complications, and
      medications. With a pseudo-prospective design, we retrieved cardiovascular death,
      major adverse cardiovascular events (MACE), and new occurrence of micro- or
      macroangiopathy during follow-up. RESULTS: At baseline, patients were on average
      60 year old, with 10-year diabetes duration, and overall poor glycaemic control
      (HbA1c 7.8%). Patients with high versus low p66Shc expression (based on median
      value) had very similar baseline characteristics. Average p66Shc expression did
      not differ by presence/absence of complications. During a median 5.6-year follow
      up, the primary endpoint of cardiovascular death or MACE occurred in 22 patients,
      but no relation was detected between cardiovascular outcomes and p66Shc
      expression. In patients who developed new complications at follow-up, baseline
      p66Shc was significantly higher, especially for macroangiopathy. The incidence of
      new macroangiopathy was > 3-times higher in patients with high versus those with
      low baseline p66Shc expression. CONCLUSIONS: p66Shc expression in PBMCs was not
      associated with prevalent diabetic complications but predicted new onset of
      complications, especially macroangiopathy, although no relation with hard
      cardiovascular endpoints was detected.

PMID- 29343270
TI  - Isolation and characterization of olfactory ecto-mesenchymal stem cells from
      eight mammalian genera.
AB  - BACKGROUND: Stem cell-based therapies are an attractive option to promote
      regeneration and repair defective tissues and organs. Thanks to their
      multipotency, high proliferation rate and the lack of major ethical limitations,
      "olfactory ecto-mesenchymal stem cells" (OE-MSCs) have been described as a
      promising candidate to treat a variety of damaged tissues. Easily accessible in
      the nasal cavity of most mammals, these cells are highly suitable for autologous
      cell-based therapies and do not face issues associated with other stem cells.
      However, their clinical use in humans and animals is limited due to a lack of
      preclinical studies on autologous transplantation and because no well-established
      methods currently exist to cultivate these cells. Here we evaluated the
      feasibility of collecting, purifying and amplifying OE-MSCs from different
      mammalian genera with the goal of promoting their interest in veterinary
      regenerative medicine. Biopsies of olfactory mucosa from eight mammalian genera
      (mouse, rat, rabbit, sheep, dog, horse, gray mouse lemur and macaque) were
      collected, using techniques derived from those previously used in humans and
      rats. The possibility of amplifying these cells and their stemness features and
      differentiation capability were then evaluated. RESULTS: Biopsies were
      successfully performed on olfactory mucosa without requiring the sacrifice of the
      donor animal, except mice. Cell populations were rapidly generated from olfactory
      mucosa explants. These cells displayed similar key features of their human
      counterparts: a fibroblastic morphology, a robust expression of nestin, an
      ability to form spheres and similar expression of surface markers (CD44, CD73).
      Moreover, most of them also exhibited high proliferation rates and clonogenicity
      with genus-specific properties. Finally, OE-MSCs also showed the ability to
      differentiate into mesodermal lineages. CONCLUSIONS: This article describes for
      the first time how millions of OE-MSCs can be quickly and easily obtained from
      different mammalian genera through protocols that are well-suited for autologous
      transplantations. Moreover, their multipotency makes them relevant to evaluate
      therapeutic application in a wide variety of tissue injury models. This study
      paves the way for the development of new fundamental and clinical studies based
      on OE-MSCs transplantation and suggests their interest in veterinary medicine.

PMID- 29343272
TI  - Biotechnologies that empower transgender persons to self-actualize as
      individuals, partners, spouses, and parents are defining new ways to conceive a
      child: psychological considerations and ethical issues.
AB  - Today, thanks to biomedical technologies advances, some persons with fertility
      issues can conceive. Transgender persons benefit also from these advances and can
      not only actualize their self-identified sexual identities but also experience
      parenthood. Based on clinical multidisciplinary seminars that gathered child
      psychiatrists and psychoanalysts interested in the fields of assisted
      reproduction technology (ART) and gender dysphoria, philosophers interested in
      bioethics, biologists interested in ART, and endocrinologists interested in
      pubertal suppression, we explore how new biotechnical advances, whether in gender
      transition or procreation, could create new ways to conceive a child possible.
      After reviewing the various medical/surgical techniques for physical gender
      transition and the current ART options, we discuss how these new ways for persons
      to self-actualize and to experience parenthood can not only improve the condition
      of transgender persons (and the human condition as a whole through greater
      equity) but also introduce some elements of change in the habitual patterns of
      thinking especially in France. Finally, we discuss the ethical issues that
      accompany the arrival of these children and provide creative solutions to help
      society handle, accept, and support the advances made in this area.

PMID- 29343273
TI  - INPP4B promotes cell survival via SGK3 activation in NPM1-mutated leukemia.
AB  - BACKGROUND: Acute myeloid leukemia (AML) with mutated nucleophosmin (NPM1) has
      been recognized as a distinct leukemia entity in the 2016 World Health
      Organization (WHO) classification. The genetic events underlying oncogenesis in
      NPM1-mutated AML that is characterized by a normal karyotype remain unclear.
      Inositol polyphosphate 4-phosphatase type II (INPP4B), a new factor in the
      phosphoinositide-3 kinase (PI3K) pathway-associated cancers, has been recently
      found a clinically relevant role in AML. However, little is known about the
      specific mechanistic function of INPP4B in NPM1-mutated AML. METHODS: The INPP4B
      expression levels in NPM1-mutated AML primary blasts and AML OCI-AML3 cell lines
      were determined by qRT-PCR and western blotting. The effect of INPP4B knockdown
      on OCI-AML3 leukemia cell proliferation was evaluated, using the Cell Counting
      Kit-8 and colony formation assay. After INPP4B overexpression or knockdown, the
      activation of serum and glucocorticoid-regulated kinase 3 (SGK3) and AKT was
      assessed. The effects of PI3K signaling pathway inhibitors on the levels of p
      SGK3 in OCI-AML3 cells were tested. The mass of PI (3,4) P2 and PI (3) P was
      analyzed by ELISA upon INPP4B overexpression. Knockdown of SGK3 by RNA
      interference and a rescue assay were performed to confirm the critical role of
      SGK3 in INPP4B-mediated cell survival. In addition, the molecular mechanism
      underlying INPP4B expression in NPM1-mutated leukemia cells was explored.
      Finally, Kaplan-Meier survival analysis was conducted on the NPM1-mutated AML
      cohort stratified into quartiles for INPP4B expression in The Cancer Genome Atlas
      (TCGA) dataset. RESULTS: High expression of INPP4B was observed in NPM1-mutated
      AML. Knockdown of INPP4B repressed cell proliferation in OCI-AML3 cells, whereas
      recovered INPP4B rescued this inhibitory effect in vitro. Mechanically, INPP4B
      enhanced phosphorylated SGK3 (p-SGK3) status, but did not affect AKT activation.
      SGK3 was required for INPP4B-induced cell proliferation in OCI-AML3 cells. High
      levels of INPP4B were at least partially caused by the NPM1 mutant via ERK/Ets-1
      signaling. Finally, high expression of INPP4B showed a trend towards lower
      overall survival and event-free survival in NPM1-mutated AML patients.
      CONCLUSIONS: Our results indicate that INPP4B promotes leukemia cell survival via
      SGK3 activation, and INPP4B might be a potential target in the treatment of NPM1
      mutated AML.

PMID- 29343274
TI  - Coexistent sickle-cell anemia and autoimmune disease in eight children: pitfalls
      and challenges.
AB  - BACKGROUND: Patients with sickle cell disease (SCD) present a defective
      activation of the alternate complement pathway that increases the risk of
      infection and is thought to predispose to autoimmune disease (AID). However,
      coexisting AID and SCD is rarely reported, suggesting possible underdiagnosis due
      to an overlapping of the symptoms. STUDY DESIGN: Among 603 patients with SCD
      followed between 1999 and June 2016, we retrospectively searched for patients
      with coexisting SCD and AID. RESULTS: We identified 8 patients aged from 7 to 17
      years diagnosed with AID; juvenile idiopathic arthritis (n = 3), systemic lupus
      erythematosus (n = 2), Sjogren's syndrome (n = 1) and autoimmune hepatitis (n =
      2). The diagnosis of AID was often delayed due to similarities of the symptoms
      with those of SCD. Patients treated with steroids experienced multiple vaso
      occlusive crises and received prophylactic chronic blood transfusions when it was
      possible. Tolerance to other immunosuppressive and biological treatments, such as
      anti-TNF agents, was good. A remission of AID was achieved in 4 patients, without
      worsening the course of the SCD. One patient underwent a geno-identical
      hematopoietic stem cell transplantation that cured both diseases. Another one
      underwent a successful liver transplantation. CONCLUSION: Coexistence of AID and
      SCD generates diagnostic and therapeutic challenges. Early diagnosis of AID is
      important to define the best treatment, which may include targeted biological
      therapy.

PMID- 29343275
TI  - Early Babesia canis transmission in dogs within 24 h and 8 h of infestation with
      infected pre-activated male Dermacentor reticulatus ticks.
AB  - BACKGROUND: This study was designed to assess the ability of fed male Dermacentor
      reticulatus ticks to transmit Babesia canis to dogs after being detached from
      previous canine or ovine hosts. METHODS: The study was an exploratory, parallel
      group design conducted in two trials. All the animals were sero-negative for
      babesiosis prior to enrolment. In a first trial, donor dogs and donor sheep were
      infested with Babesia canis infected male and uninfected female ticks for 72 h.
      The ticks were detached and the second group of host dogs were infested for 24 h
      before tick removal. In a second trial, the experiment was repeated but the donor
      animals were infested for 88 h and the second group of host dogs were infested
      for 8 h prior to tick removal. After infestation, the dogs were maintained under
      clinical surveillance and blood samples were collected for blood smear, IFA and
      PCR analysis. A dog was considered infected if any of these tests were positive.
      RESULTS: All of the dogs (6 out of 6) were infected after being exposed to pre
      activated male ticks for 24 h. Half of the dogs were infected after being exposed
      to pre-activated ticks for 8 h: 1 out of 3 dogs infested with ticks removed from
      sheep and 2 out of 3 dogs infested with ticks removed from dog. All the infected
      dogs were positive to blood smear, IFA and PCR. Three of these dogs exhibited
      elevated body temperature (> 39.4  degrees C). CONCLUSIONS: This study
      demonstrates the ability of male D. reticulatus to transmit B. canis to dogs. The
      study also illustrates for the first time that, regardless of the first host on
      which ticks may attach and start feeding, Babesia canis can be transmitted to
      dogs within 8 h of infestation. Since no minimal transmission time can be
      established for all possible natural situations, a strategy of prevention based
      on anti-attachment or repellency is recommended.

PMID- 29343277
TI  - First molecular detection and genetic characterization of Coxiella burnetii in
      Zambian dogs and rodents.
AB  - Coxiella burnetii, the causative agent of Q fever, is a zoonotic pathogen
      associated with sylvatic or domestic transmission cycles, with rodents being
      suspected to link the two transmission cycles. Infection and subsequent disease
      in humans has historically been associated with contact with infected livestock,
      especially sheep. However, recently there have been reports of Q fever outbreaks
      associated with contact with infected rodents and dogs. Studies exploring the
      potential role of these animal hosts in the epidemiology of Q fever in many
      developing countries in Africa are very limited. This study aimed to determine
      the potential role of rodents and dogs in the epidemiological cycle of C.
      burnetti in Zambia. Using pathogen-specific polymerase chain reaction assays
      targeting the 16S rRNA gene, C. burnetii was detected for the first time in 45%
      of rodents (9/20), in one shrew and in 10% of domestic dogs (15/150) screened in
      Zambia. Phylogenetic characterization of six samples based on the isocitrate
      synthase gene revealed that the strains were similar to a group of isolates from
      chronic human Q fever patients, goats and rodents reported in multiple
      continents. Considering the close proximity of domestic dogs and rodents to
      humans, especially in resource-limited communities, the presence of C. burnetii
      in these animals could be of significant public health importance. It is thus
      important to determine the burden of Q fever in humans in such resource-limited
      communities where there is close contact between humans, rodents and dogs.

PMID- 29343276
TI  - The antihyperlipidemic effects of fullerenol nanoparticles via adjusting the gut
      microbiota in vivo.
AB  - BACKGROUND: Nanoparticles (NPs) administered orally will meet the gut microbiota,
      but their impacts on microbiota homeostasis and the consequent physiological
      relevance remain largely unknown. Here, we describe the modulatory effects and
      the consequent pharmacological outputs of two orally administered fullerenols NPs
      (Fol1 C60(OH)7(O)8 and Fol113 C60(OH)11(O)6) on gut microbiota. RESULTS:
      Administration of Fol1 and Fol113 NPs for 4 weeks largely shifted the overall
      structure of gut microbiota in mice. The bacteria belonging to putative short
      chain fatty acids (SCFAs)-producing genera were markedly increased by both NPs,
      especially Fol1. Dynamic analysis showed that major SCFAs-producers and key
      butyrate-producing gene were significantly enriched after treatment for 7-28
      days. The fecal contents of SCFAs were consequently increased, which was
      accompanied by significant decreases of triglycerides and total cholesterol
      levels in the blood and liver, with Fol1 superior to Fol113. Under cultivation in
      vitro, fullerenols NPs can be degraded by gut flora and exhibited a similar
      capacity of inulin to promote SCFA-producing genera. The differential effects of
      Fol1 and Fol113 NPs on the microbiome may be attributable to their subtly varied
      surface structures. CONCLUSIONS: The two fullerenol NPs remarkably modulate the
      gut microbiota and selectively enrich SCFA-producing bacteria, which may be an
      important reason for their anti-hyperlipidemic effect in mice.

PMID- 29343278
TI  - Lipoblastoma: a clinicopathologic review of 23 cases from a major tertiary care
      center plus detailed review of literature.
AB  - OBJECTIVE: Lipoblastoma is a rare neoplasm that occurs mostly in infants and
      children. Although benign, it has a tendency for local recurrence. RESULTS:
      Clinical and pathological features of 23 cases of lipoblastoma described.
      Patients' age ranged from 8 months to 18 years with mean and median age 4.1 and
      2.5 years, respectively. Male:female ratio was 2.8:1. Most common sites were
      lower extremities (9 cases), followed by abdominal cavity and retroperitoneum (4
      cases), and scrotum/groin (3 cases). Grossly, 22 tumors were well circumscribed
      and multi nodular. All cases showed lobules composed of adipocytes and lipoblasts
      with intervening fibrous septa and fine vascular network. Myxoid change, capsule
      formation and septation were seen in all cases. Zonation was seen in 2 cases.
      Follow-up was available in 14 out of 23 patients. Of these, 13 were alive and
      free of disease with no evidence of any recurrent lesion. One patient with a
      mediastinal infiltrating lipoblastoma experienced 4 recurrences. Lipoblastoma is
      a benign adipocytic neoplasm of infants and young children. Correlation of
      clinical and histological features helps in reaching a correct diagnosis. Owing
      to a high recurrence rate following incomplete resection, a complete resection is
      essential. Prognosis is excellent after complete resection.

PMID- 29343279
TI  - Spatial distribution and habitat characterization of mosquito species during the
      dry season along the Mara River and its tributaries, in Kenya and Tanzania.
AB  - BACKGROUND: Vector-borne diseases are increasingly becoming a major health
      problem among communities living along the major rivers of Africa. Although
      larger water bodies such as lakes and dams have been extensively researched,
      rivers and their tributaries have largely been ignored. This study sought to
      establish the spatial distribution of mosquito species during the dry season and
      further characterize their habitats along the Mara River and its tributaries.
      METHODS: In this cross-sectional survey, mosquito larvae were sampled along the
      Mara River, its two perennial tributaries (Amala and Nyangores), drying streams,
      and adjacent aquatic habitats (e.g. swamps, puddles that receive direct sunlight
      [open sunlit puddles], rock pools, hippo and livestock hoof prints, and vegetated
      pools). Each habitat was dipped 20 times using a standard dipper. Distance
      between breeding sites and human habitation was determined using global
      positioning system coordinates. The collected mosquito larvae were identified
      using standard taxonomic keys. Water physico-chemical parameters were measured in
      situ using a multiparameter meter. Mean mosquito larvae per habitat type were
      compared using analysis of variance and chi-square tests, while the relationship
      between mosquito larvae and physico-chemical parameters was evaluated using a
      generalized linear mixed model. The Cox-Stuart test was used to detect trends of
      mosquito larvae distribution. The test allowed for verification of monotonic
      tendency (rejection of null hypothesis of trend absence) and its variability.
      RESULTS: A total of 4001 mosquito larvae were collected, of which 2712 (67.8%)
      were collected from river/stream edge habitats and 1289 (32.2%) were sampled from
      aquatic habitats located in the terrestrial ecosystem about 50 m away from the
      main river/streams. Anopheles gambiae s.s, An. arabiensis, and An. funestus
      group, the three most potent vectors of malaria in Sub-Saharan Africa, together
      with other anopheline mosquitoes, were the most dominant mosquito species
      (70.3%), followed by Culex quinquefasciatus and Cx. pipiens complex combined
      (29.5%). Drying streams accounted for the highest number of larvae captured
      compared to the other habitat types. A stronger relationship between mosquito
      larvae abundance and dissolved oxygen (Z = 7.37, P <= 0.001), temperature (Z =
      7.65, P <= 0.001), turbidity (Z = -5.25, P <= 0.001), and distance to the nearest
      human habitation (Z = 4.57, P <= 0.001), was observed. CONCLUSIONS: Presence of
      malaria and non-malaria mosquito larvae within the Mara River basin calls for
      immediate action to curtail the insurgence of vector-borne diseases within the
      basin. A vector control program should be conducted during the dry period,
      targeting drying streams shown to produce the highest number of larval
      mosquitoes.

PMID- 29343280
TI  - Pregabalin versus placebo in targeting pro-nociceptive mechanisms to prevent
      chronic pain after whiplash injury in at-risk individuals - a feasibility study
      for a randomised controlled trial.
AB  - BACKGROUND: Whiplash-associated disorders (WAD) are an enormous and costly burden
      to Australian society. Up to 50% of people who experience a whiplash injury will
      never fully recover. Whiplash is resistant to treatment and no early management
      approach has yet been shown to prevent chronic pain. The early presence of
      central sensitization is associated with poor recovery. Pregabalin's effects on
      central sensitization indicate the potential to prevent or modulate these
      processes after whiplash injury and to improve health outcomes, but this has not
      been investigated. This paper describes the protocol for a feasibility study for
      a randomised controlled trial of pregabalin plus evidence-based advice compared
      to placebo plus evidence-based advice for individuals with acute whiplash injury
      who are at risk of poor recovery. METHODS: This double blind, placebo-controlled
      randomised feasibility study will examine the feasibility and potential
      effectiveness of pregabalin and evidence-based advice (intervention) compared to
      placebo and evidence-based advice (control) for individuals with acute whiplash
      injury at risk of poor recovery. Thirty participants (15 per group) aged 18-65
      years with Grade II WAD, within 48 hours of injury and currently experiencing at
      least moderate pain (NRS: >= 5/10) will be recruited from Emergency Departments
      of public hospitals in Queensland, Australia. Pregabalin will be commenced at 75
      mg bd and titrated up to 300 mg bd as tolerated for 4 weeks followed by 1 week of
      weaning. RESULTS: The feasibility of trial procedures will be tested, as well as
      the potential effect of the intervention on the outcomes. The primary outcome of
      neck pain intensity at 3 months from randomisation will be compared between the
      treatment groups using standard analysis of variance techniques. DISCUSSION:
      Feasibility and potential effectiveness data will inform an appropriately powered
      full trial, which if successful, will provide an effective and cost-effective
      intervention for a costly and treatment resistant condition. It will also have
      implications for the early management of other traumatic conditions beyond
      whiplash. TRIAL REGISTRATION: Clinical Trials Primary Registry: Australian and
      New Zealand Clinical Trials Registry. CLINICAL TRIAL REGISTRATION NUMBER:
      ACTRN12617000059369 . Date of Registration: 11/01/2017. Primary Trial Sponsor:
      The University of Queensland, Brisbane QLD 4072 Australia.

PMID- 29343281
TI  - P-MAPA immunotherapy potentiates the effect of cisplatin on serous ovarian
      carcinoma through targeting TLR4 signaling.
AB  - BACKGROUND: Toll-like receptors (TLRs) are transmembrane proteins expressed on
      the surface of ovarian cancer (OC) and immune cells. Identifying the specific
      roles of the TLR-mediated signaling pathways in OC cells is important to guide
      new treatments. Because immunotherapies have emerged as the adjuvant treatment
      for patients with OC, we investigated the effect of a promising immunotherapeutic
      strategy based on protein aggregate magnesium-ammonium phospholinoleate
      palmitoleate anhydride (P-MAPA) combined with cisplatin (CIS) on the TLR2 and
      TLR4 signaling pathways via myeloid differentiation factor 88 (MyD88) and TLR
      associated activator of interferon (TRIF) in an in vivo model of OC. METHODS:
      Tumors were chemically induced by a single injection of 100 MUg of 7,12
      dimethylbenz(a)anthracene (DMBA) directly under the left ovarian bursa in Fischer
      344 rats. After the rats developed serous papillary OC, they were given P-MAPA,
      CIS or the combination P-MAPA+CIS as therapies. To understand the effects of the
      treatments, we assessed the tumor size, histopathology, and the TLR2- and TLR4
      mediated inflammatory responses. RESULTS: Although CIS therapy was more effective
      than P-MAPA in reducing the tumor size, P-MAPA immunotherapy significantly
      increased the expressions of TLR2 and TLR4. More importantly, the combination of
      P-MAPA with CIS showed a greater survival rate compared to CIS alone, and
      exhibited a significant reduction in tumor volume compared to P-MAPA alone. The
      combination therapy also promoted the increase in the levels of the following OC
      related proteins: TLR4, MyD88, TRIF, inhibitor of phosphorylated NF-kB alpha (p
      IkBalpha), and nuclear factor kappa B (NF-kB p65) in both cytoplasmic and nuclear
      sites. While P-MAPA had no apparent effect on tumor necrosis factor alpha (TNF
      alpha) and interleukin (IL)-6, it seems to increase interferon-gamma (IFN-gamma),
      which may induce the Thelper (Th1)-mediated immune response. CONCLUSION:
      Collectively, our results suggest that P-MAPA immunotherapy combined with
      cisplatin could be considered an important therapeutic strategy against OC cells
      based on signaling pathways activated by TLR4.

PMID- 29343282
TI  - Investigation of perioperative safety and clinical results of one-stage bilateral
      total knee arthroplasty in selected low-risk patients.
AB  - BACKGROUND: An increased perioperative complication rate has been a concern with
      one-stage bilateral total knee arthroplasty (TKA). The purpose of this study was
      to retrospectively investigate the perioperative safety and clinical results of
      one-stage bilateral TKA in selected low-risk patients. METHODS: Sixty-seven
      patients who received one-stage bilateral TKAs for osteoarthritis who were
      American Society of Anesthesiology (ASA) class 1 or 2 were included in this
      study. Perioperative complications, blood loss, transfusion rate, blood
      laboratory results, and clinical results were evaluated up to 1 year after
      surgery. RESULTS: No major complications (deep infection, pulmonary embolism,
      cerebrovascular accident, myocardial infarction, death, or removal or revision of
      the implants) were observed. The average total blood loss was 1139.5 ml. The
      transfusion rate was 95.5%. Postoperative hemoglobin level and C-reactive protein
      level gradually improved up to postoperative day 21 (P < 0.01). Bilateral knee
      extension knee angles and clinical scores improved postoperatively as compared
      with preoperative values (P < 0.01). CONCLUSIONS: Although total blood loss and
      transfusion rate can be high, this preliminary case series suggested that the one
      stage bilateral TKA in ASA class 1 or 2 patients can have high perioperative
      safety levels, and good clinical results can be obtained up to 1 year after
      surgery. If low-risk patients are selected for bilateral TKA, a one-stage
      procedure can be beneficial for patients, with a minimal increase in the risk of
      complications.

PMID- 29343283
TI  - The Classroom Communication Resource (CCR) intervention to change peer's
      attitudes towards children who stutter (CWS): study protocol for a randomised
      controlled trial.
AB  - BACKGROUND: Children who stutter (CWS) are at a high-risk of being teased and
      bullied in primary school because of negative peer attitudes and perceptions
      towards stuttering. There is little evidence to determine if classroom-based
      interventions are effective in changing peer attitudes towards stuttering. The
      primary objective is to determine the effect of the Classroom Communication
      Resource (CCR) intervention versus usual practice, measured using the Stuttering
      Resource Outcomes Measure (SROM) 6-months post-intervention among grade 7
      students. The secondary objective is to investigate attitude changes towards
      stuttering among grade participants on the SROM subscales. METHODS: A cluster
      randomised controlled trial (RCT) will be conducted with schools as the unit of
      randomization. Schools will be stratified into quintile groups, and then
      randomized to receive the CCR intervention or usual practice. Quintile
      stratification will be conducted in accordance to the Western Cape Department of
      Education classification of schools according to geographical location, fee per
      school and allocation of resources and funding. Participants will include primary
      schools in the lower (second and third) and higher (fourth and fifth) quintiles
      and children aged 11 years or older in grade 7 will be included. The study will
      consist of the CCR intervention program or usual practice as a no-CCR control.
      The CCR is a classroom-based, teacher led intervention tool including a story,
      role-play and discussion. The grade 7 teachers allocated to the CCR intervention,
      will be trained and will administer the intervention. The analysis will follow
      intention-to-treat (ITT) principle and generalized estimating equations (GEE) to
      compare groups on the global SROM and its subscales to account for possible
      clustering within schools. The subgroup hypothesis will be tested by adding an
      interaction term of quintile group x intervention. DISCUSSION: This study is
      designed to assess whether the CCR intervention versus usual practice in schools
      will lead to positive shift in attitudes about stuttering at 6-months post
      intervention among grade 7 participants. TRIAL REGISTRATION: The trial number is
      NCT03111524 . It was registered with clinical trials.gov Protocol registration
      and results system (PRS) retrospectively on 9 March 2017.

PMID- 29343284
TI  - Extensive ARMC5 genetic variance in primary bilateral macronodular adrenal
      hyperplasia that started with exophthalmos: a case report.
AB  - BACKGROUND: Primary bilateral macronodular adrenal hyperplasia is a rare cause of
      Cushing's syndrome characterized by the presence of bilateral secretory adrenal
      nodules. Recent studies have shown that primary bilateral macronodular adrenal
      hyperplasia is caused by combined germline and somatic mutations of the ARMC5
      gene. Exophthalmos is an underappreciated sign of Cushing's syndrome. CASE
      PRESENTATION: A 52-year-old Chinese woman with progressively worsening bilateral
      proptosis presented to our hospital. Subsequently she was diagnosed as having
      primary bilateral macronodular adrenal hyperplasia and underwent bilateral
      laparoscopic adrenalectomy. Genomic deoxyribonucleic acid was isolated from
      lymphocytes as well as seven different adrenal nodules and the ARMC5 sequence was
      determined by Sanger sequencing. We identified one heterozygous ARMC5 germline
      mutation c.682C>T (p. Gln228*) and five heterozygous somatic mutations
      (c.310delG, c.347_357del11, c.267delC, c.283_289del7, and c.205-322del118) in
      five different adrenal nodules. All mutations are novel and were not found in any
      of the available online databases. To test whether the ARMC5 mutation induced
      messenger ribonucleic acid decay, real-time reverse transcriptase polymerase
      chain reaction was performed on patient and control adrenal tissue. We found that
      the adrenal cortex of our patient showed a low ARMC5 messenger ribonucleic acid
      expression compared with normal adrenal cortex, possibly as a result of nonsense
      mediated messenger ribonucleic acid decay CONCLUSIONS: We demonstrated extensive
      genetic diversity of ARMC5 in a patient with primary bilateral macronodular
      adrenal hyperplasia that started with exophthalmos, which contributes to further
      understanding of the pathogenesis of this disease. Early recognition of atypical
      symptoms and screening for ARMC5 mutation in patients with primary bilateral
      macronodular adrenal hyperplasia has important clinical implications for the
      diagnosis and genetic counseling.

PMID- 29343285
TI  - Cyberbullying a modern form of bullying: let's talk about this health and social
      problem.
AB  - Cyberbullying or electronic aggression has already been designated as a serious
      public health threat. Cyberbullying should also be considered as a cause for new
      onset psychological symptoms, somatic symptoms of unclear etiology or a drop in
      academic performance. Pediatricians should be trained to play a major role in
      caring for and supporting the social and developmental well-being of children.

PMID- 29343287
TI  - Percutaneous kyphoplasty for the treatment of very severe osteoporotic vertebral
      compression fractures with spinal canal compromise.
AB  - BACKGROUND: Very severe osteoporotic vertebral compression fractures (vsOVCFs)
      are osteoporotic vertebral compression fractures with vertebral body collapse to
      less than one third of their original height. Few data are available about the
      use of percutaneous kyphoplasty (PKP) in treating vsOVCFs with spinal canal
      compromise. The aim of this study was to evaluate the safety and efficacy of
      percutaneous kyphoplasty (PKP) for the treatment of vsOVCFs with spinal canal
      compromise. METHODS: Thirty-five patients who suffered vsOVCFs with spinal canal
      compromise but without neurological deficits were treated by PKP between January
      2009 and October 2014. The vertebral height, local kyphotic angle (LKA), visual
      analogue scale (VAS) and Oswestry Disability Index (ODI) values were assessed
      before the operation, 1 day after the operation and at the final follow-up.
      RESULTS: Significant improvements on the VAS and ODI were noted 1 day post
      operatively (p < 0.01), and these results were preserved at the final follow-up.
      The vertebral height was restored and the LKA was improved after surgery (p <
      0.01). No neurological deterioration was found. Five of 35 vertebrae (14.3%) of
      cement leakages were all asymptomatic. Four new OVCFs in three patients were
      identified. CONCLUSION: PKP is a safe and effective procedure for the treatment
      of vsOVCFs with spinal canal compromise, achieving significant vertebral height
      restoration and kyphotic angle reduction and leading to a significant pain relief
      and improvement in function.

PMID- 29343286
TI  - Diagnosis and management of transthyretin familial amyloid polyneuropathy in
      Japan: red-flag symptom clusters and treatment algorithm.
AB  - Hereditary ATTR (ATTRm) amyloidosis (also called transthyretin-type familial
      amyloid polyneuropathy [ATTR-FAP]) is an autosomal-dominant, adult-onset, rare
      systemic disorder predominantly characterized by irreversible, progressive, and
      persistent peripheral nerve damage. TTR gene mutations (e.g. replacement of
      valine with methionine at position 30 [Val30Met (p.Val50Met)]) lead to
      destabilization and dissociation of TTR tetramers into variant TTR monomers,
      which form amyloid fibrils that deposit in peripheral nerves and various organs,
      giving rise to peripheral and autonomic neuropathy and several non-disease
      specific symptoms.Phenotypic and genetic variability and non-disease-specific
      symptoms often delay diagnosis and lead to misdiagnosis. Red-flag symptom
      clusters simplify diagnosis globally. However, in Japan, types of TTR variants,
      age of onset, penetrance, and clinical symptoms of Val30Met are more varied than
      in other countries. Hence, development of a Japan-specific red-flag symptom
      cluster is warranted. Presence of progressive peripheral sensory-motor
      polyneuropathy and >=1 red-flag sign/symptom (e.g. family history, autonomic
      dysfunction, cardiac involvement, carpal tunnel syndrome, gastrointestinal
      disturbances, unexplained weight loss, and immunotherapy resistance) suggests
      ATTR-FAP. Outside of Japan, pharmacotherapeutic options are first-line therapy.
      However, because of positive outcomes (better life expectancy and higher survival
      rates) with living donor transplant in Japan, liver transplantation remains first
      line treatment, necessitating a Japan-specific treatment algorithm.Herein, we
      present a consolidated review of the ATTR-FAP Val30Met landscape in Japan and
      summarize findings from a medical advisory board meeting held in Tokyo on 18th
      August 2016, at which a Japan-specific ATTR-FAP red-flag symptom cluster and
      treatment algorithm was developed. Beside liver transplantation, a TTR
      stabilizing agent (e.g. tafamidis) is a treatment option. Early diagnosis and
      timely treatment using the Japan-specific red-flag symptom cluster and treatment
      algorithm might help guide clinicians regarding apt and judicious use of
      available treatment modalities.

PMID- 29343288
TI  - Changes in the secretome of tri-dimensional spheroid-cultured human mesenchymal
      stem cells in vitro by interleukin-1 priming.
AB  - BACKGROUND: Mesenchymal stem cells (MSCs) are one of the most promising
      candidates for the treatment of major neurological disorders. Desirable
      therapeutic properties of MSCs include reparative and regenerative potential but,
      despite their proven safety, the efficacy of MSCs remains controversial.
      Therefore, it is essential to optimise culture protocols to enhance the
      therapeutic potential of the MSC secretome. Here we aimed to: assess the increase
      in secretion of cytokines that may induce repair, regeneration, or
      immunomodulation when cultured in three dimensions; study the effect of
      interleukin (IL)-1 priming on two- (2D) and three-dimensional (3D) cultures of
      MSC; and evaluate the potential use of the modified secretome using microglial
      MSC co-cultures. METHODS: We established a 3D spheroid culture of human MSCs, and
      compared the secretome in 2D and 3D cultures under primed (IL-1) and unprimed
      conditions. BV2 microglial cells were stimulated with lipopolysaccharide (LPS)
      and treated with spheroid conditioned media (CM) or were co-cultured with whole
      spheroids. Concentrations of secreted cytokines were determined by enzyme-linked
      immunosorbent assay (ELISA). Protein arrays were used to further evaluate the
      effect of IL-1 priming in 2D and 3D cultures. RESULTS: 3D culture of MSCs
      significantly increased secretion of the IL-1 receptor antagonist (IL-1Ra),
      vascular endothelial growth factor (VEGF), and granulocyte-colony stimulating
      factor (G-CSF) compared with 2D culture, despite priming treatments with IL-1
      being more effective in 2D than in 3D. The addition of CM of 3D-MSCs reduced LPS
      induced tumour necrosis factor (TNF)-alpha secretion from BV2 cells, while the 3D
      spheroid co-cultured with the BV2 cells induced an increase in IL-6, but had no
      effect on TNF-alpha release. Protein arrays indicated that priming treatments
      trigger a more potent immune profile which is necessary to orchestrate an
      effective tissue repair. This effect was lost in 3D, partly because of the
      overexpression of IL-6. CONCLUSIONS: Increased secretion of anti-inflammatory
      markers occurs when MSCs are cultured in 3D, but this specific secretome did not
      translate into anti-inflammatory effects on LPS-treated BV2 cells in co-culture.
      These data highlight the importance of optimising priming treatments and culture
      conditions to maximise the therapeutic potential of MSC spheroids.

PMID- 29343289
TI  - Differentiated thyroid carcinoma presentation may be more aggressive in children
      and adolescents than in young adults.
AB  - BACKGROUND: The available studies concerning the influence of age on the
      phenotypical expression of differentiated thyroid carcinoma (DTC) have hitherto
      compared DTC presentation either between pre-pubertal and pubertal children or
      between pediatric patients and aged adults; aim of this study was to ascertain
      for the first time whether presentation of DTC may significantly vary according
      to age, even within a peculiar study population covering only young patients aged
      less than 30 years. METHODS: The main clinical, biochemical and pathologic data
      at DTC diagnosis were retrospectively recorded in 2 selected cohorts including,
      respectively, 18 children and adolescents aged less than 18 years (Group A) or 45
      young adults aged between 20 and 29.8 years (Group B). RESULTS: The statistical
      distribution of DTC cases in the different age ranges was found to progressively
      increase with increasing age; furthermore, the patients of Group A exhibited at
      diagnosis a more severe clinical involvement and a higher rate of extra-regional
      metastases; finally, also the association with both autoimmune thyroid diseases
      (AITDs) and a biochemical hypothyroid pattern was more common in Group A
      patients. CONCLUSIONS: In a study population younger than 30 years: a) the risk
      of developing DTC increases with age, achieving its zenith during the 3rd decade
      of life; b) clinical presentation is more severe in children and adolescents
      younger than 18 years than in the patients aged between 20 and 30; c) in the
      cohort of children and adolescents DTC is more often associated with AITDs, which
      might play some role in conditioning the more aggressive phenotypical
      presentation of DTC in this patient group.

PMID- 29343291
TI  - Trends in the performance of quality indicators for diabetes care in the
      community and in diabetes-related health status: an Israeli ecological study.
AB  - BACKGROUND: Israel is one of the few countries that have a national program for
      quality assessment of community healthcare. We aimed to evaluate whether improved
      performance in diabetes care was associated with improved health of diabetic
      patients on a national level. METHODS: We conducted a nationwide ecological study
      estimating improvements in diabetes-related quality indicators and health
      outcomes. We estimated both correlations between composite measures of diabetes
      related quality indicators and selected outcomes, and assessed through a
      joinpoint analysis whether trends in selected outcomes changed 4 years after the
      inception of the national program. RESULTS: Between 2002 and 2010, the prevalence
      of diabetes in Israeli adults increased from 4.8% to 7.4%. During these years, an
      improvement was noticed in most quality indicators (from 53% to 75% for the
      composite score). Declines were noted in rates of blindness, diabetes-related end
      stage kidney disease, lower limbs amputations and diabetes-related mortality.
      Significant accelerations in decline were noted for amputations in men and
      diabetes-related mortality in both Arab men and women 4 years after the inception
      of the national program. CONCLUSION: This study suggests that Israel's national
      program for quality indicators in diabetes care in the community has probably had
      a significant impact on the health status of the whole population and may have
      contributed to narrowing gaps in life expectancy between Israeli Jews and Arabs.
      Future studies based on individual-level data are needed to confirm these
      results.

PMID- 29343290
TI  - FineMAV: prioritizing candidate genetic variants driving local adaptations in
      human populations.
AB  - We present a new method, Fine-Mapping of Adaptive Variation (FineMAV), which
      combines population differentiation, derived allele frequency, and molecular
      functionality to prioritize positively selected candidate variants for functional
      follow-up. We calibrate and test FineMAV using eight experimentally validated
      "gold standard" positively selected variants and simulations. FineMAV has good
      sensitivity and a low false discovery rate. Applying FineMAV to the 1000 Genomes
      Project Phase 3 SNP dataset, we report many novel selected variants, including
      ones in TGM3 and PRSS53 associated with hair phenotypes that we validate using
      available independent data. FineMAV is widely applicable to sequence data from
      both human and other species.

PMID- 29343292
TI  - Global trends in the awareness of sepsis: insights from search engine data
      between 2012 and 2017.
AB  - BACKGROUND: Sepsis is an established global health priority with high mortality
      that can be curtailed through early recognition and intervention; as such,
      efforts to raise awareness are potentially impactful and increasingly common. We
      sought to characterize trends in the awareness of sepsis by examining temporal,
      geographic, and other changes in search engine utilization for sepsis information
      seeking online. METHODS: Using time series analyses and mixed descriptive
      methods, we retrospectively analyzed publicly available global usage data
      reported by Google Trends (Google, Palo Alto, CA, USA) concerning web searches
      for the topic of sepsis between 24 June 2012 and 24 June 2017. Google Trends
      reports aggregated and de-identified usage data for its search products,
      including interest over time, interest by region, and details concerning the
      popularity of related queries where applicable. Outlying epochs of search
      activity were identified using autoregressive integrated moving average modeling
      with transfer functions. We then identified awareness campaigns and news media
      coverage that correlated with epochs of significantly heightened search activity.
      RESULTS: A second-order autoregressive model with transfer functions was
      specified following preliminary outlier analysis. Nineteen significant outlying
      epochs above the modeled baseline were identified in the final analysis that
      correlated with 14 awareness and news media events. Our model demonstrated that
      the baseline level of search activity increased in a nonlinear fashion. A
      recurrent cyclic increase in search volume beginning in 2012 was observed that
      correlates with World Sepsis Day. Numerous other awareness and media events were
      correlated with outlying epochs. The average worldwide search volume for sepsis
      was less than that of influenza, myocardial infarction, and stroke. CONCLUSIONS:
      Analyzing aggregate search engine utilization data has promise as a mechanism to
      measure the impact of awareness efforts. Heightened information-seeking about
      sepsis occurs in close proximity to awareness events and relevant news media
      coverage. Future work should focus on validating this approach in other contexts
      and comparing its results to traditional methods of awareness campaign
      evaluation.

PMID- 29343293
TI  - Identification of preoperative prediction factors of tumor subtypes for patients
      with solitary ground-glass opacity pulmonary nodules.
AB  - BACKGROUND: Recent wide spread use of low-dose helical computed tomography for
      the screening of lung cancer have led to an increase in the detection rate of
      very faint and smaller lesions known as ground-glass opacity nodules. The purpose
      of this study was to investigate the clinical factors of lung cancer patients
      with solitary ground-glass opacity pulmonary nodules on computed tomography.
      METHODS: A total of 423 resected solitary ground-glass opacity nodules were
      retrospectively evaluated. We analyzed the clinical, imaging and pathological
      data and investigated the clinical differences in patient with adenocarcinoma in
      situ / minimally invasive adenocarcinoma and those with invasive adenocarcinoma.
      RESULTS: Three hundred and ninety-three adenocarcinomas (92.9%) and 30 benign
      nodules were diagnosed. Age, the history of family cancer, serum carcinoembryonic
      antigen level, tumor size, ground-glass opacity types, and bubble-like sign in
      chest CT differed significantly between adenocarcinoma in situ / minimally
      invasive adenocarcinoma and invasive adenocarcinoma (p:0.008, 0.046, 0.000,
      0.000, 0.000 and 0.001). Receiver operating characteristic curves and univariate
      analysis revealed that patients with more than 58.5 years, a serum
      carcinoembryonic antigen level > 1.970 MUg/L, a tumor size> 13.50 mm, mixed
      ground-glass opacity nodules and a bubble-like sign were more likely to be
      diagnosed as invasive adenocarcinoma. The combination of five factors above had
      an area under the curve of 0.91, with a sensitivity of 82% and a specificity of
      87%. CONCLUSION: The five-factor combination helps us to distinguish
      adenocarcinoma in situ / minimally invasive adenocarcinoma from invasive
      adenocarcinoma and to perform appropriate surgery for solitory ground-glass
      opacity nodules.

PMID- 29343294
TI  - Effect of glycaemic control on complications following cardiac surgery:
      literature review.
AB  - INTRODUCTION: No uniform consensus in the UK or Europe exists, for glycaemic
      management of patients with Diabetes or pre-diabetes undergoing cardiac surgery.
      OBJECTIVE: [i] Determine the relationship between glycaemic control and cardiac
      surgical outcomes; [ii] Compare current vs gold standard management of patients
      with Diabetes or pre-diabetes undergoing cardiac surgery. METHODS: Searches of
      MEDLINE, NHS Evidence and Web of Science databases were completed. Articles were
      limited to those in English, German and French. No date limit was enforced.13,232
      articles were identified on initial literature review, and 50 relevant papers
      included in this review. RESULTS: No national standards for glycaemic control
      prior to cardiac surgery were identified. Upto 30% of cardiac surgical patients
      have undiagnosed Diabetes. Cardiac surgical patients without Diabetes with pre
      operative hyperglycaemia have a 1 year mortality double that of patients with
      normoglyacemia, and equivalent to patients already diagnosed with Diabetes. Pre-
      and peri-operative hyperglycaemia is associated with worse outcomes. Evidence
      regarding tight glycaemic control vs moderate glycaemic control is conflicting.
      Tight control may be more effective in patients without Diabetes with pre-/peri
      operative hyperglycaemia, and moderate control appears more effective in patients
      with pre-existing Diabetes. Patients with well controlled Diabetes may achieve
      comparable outcomes to patients without Diabetes with similar glycaemic control.
      CONCLUSIONS: Pre / peri-operative hyperglycaemia is associated with worse
      outcomes in both patients with, and without Diabetes undergoing CABG. This review
      supports the pre-operative screening, and optimisation of glycaemic control in
      patients undergoing cardiac surgery. Optimal glycaemic management remains unclear
      and clear guidelines are needed.

PMID- 29343295
TI  - Cytotoxic T lymphocytes from cattle sharing the same MHC class I haplotype and
      immunized with live Theileria parva sporozoites differ in antigenic specificity.
AB  - OBJECTIVES: The objective of this study was to assess whether cytotoxic T cells
      (CTL) generated by the live vaccine, known as "ITM Muguga cocktail", which is
      used for the cattle disease East Cost fever (ECF) in Sub-Saharan Africa, showed a
      broad reactivity against many different strains of the causative parasite
      Theileria parva. We also assessed whether immune responses were similar in cattle
      expressing the same MHC class I haplotypes. RESULTS: The antigenic specificity of
      CTL from MHC class I-matched cattle vaccinated with the Muguga cocktail were
      different. Three cattle of MHC class I haplotype A18, one A18/A19 and two
      haploidentical (A18v/A12) animals, showed differential recognition of autologous
      cells infected with a panel of T. parva isolates. This could have implications in
      the field where certain strains could break through the vaccine. Furthermore,
      neither of the haploidentical cattle recognized the CTL epitope (Tp1214-224),
      presented by the A18 haplotype, in contrast to the third animal, showing
      differences in immunodominance in animals of the same haplotype A18. This
      suggests that the CTL specificities following immunization with the Muguga
      cocktail can vary even between haploidentical individuals and that some parasite
      strains may break through immunity generated by the Muguga cocktail.

PMID- 29343296
TI  - Quantitative method for analysis of six anticoagulant rodenticides in faeces,
      applied in a case with repeated samples from a dog.
AB  - BACKGROUND: Accidental poisoning with anticoagulant rodenticides is not uncommon
      in dogs, but few reports of the elimination kinetics and half-lives in this
      species have been published. Our objectives were to develop and validate a new
      method for the quantification of anticoagulant rodenticides in canine blood and
      faeces using reversed phase ultra-high performance liquid chromatography-tandem
      mass spectrometry (UHPLC-MS/MS) and apply the method on a case of anticoagulant
      rodenticide intoxication. RESULTS: Sample preparation was liquid-liquid
      extraction. Six anticoagulant rodenticides were separated using a UPLC(r) BEH C18
      column with a mobile phase consisting of 5 mM ammonium formate buffer pH 10.2 and
      methanol. MS/MS detection was performed with positive electrospray ionization and
      two multiple reaction monitoring transitions. The limits of quantification were
      set at the levels of the lowest calibrator (1.5-2.7 ng/mL or ng/g). The method
      was successfully applied to a case from a dog accidentally poisoned with
      anticoagulant rodenticide. Coumatetralyl and brodifacoum concentrations were
      determined from serial blood and faecal samples. A terminal half-life of at least
      81 days for coumatetralyl in blood was estimated, which is longer than previous
      reported in other species. A slow elimination of brodifacoum from the faeces was
      found, with traces still detectable in the faeces at day 513. CONCLUSIONS: This
      study offers a new method of detection and quantification of six frequently used
      anticoagulant rodenticides in canine faeces. Such drugs might cause serious
      health effects and it is important to be able to detect these drugs, to initiate
      proper treatment. The very long elimination half-lives detected in our study is
      important to be aware of in assessment of anticoagulant rodenticide burden to the
      environment.

PMID- 29343297
TI  - Pulmonary valve replacement after right ventricular outflow tract reconstruction
      with homograft vs Contegra(r): a case control comparison of mortality and
      morbidity.
AB  - BACKGROUND: Repair of congenital heart defects involving the right ventricular
      outflow tract may require the implantation of a right ventricle to pulmonary
      artery conduit. This conduit is likely to be replaced during childhood. This
      study compares the operative outcomes of the replacement procedure of Contegra(r)
      and homografts in pulmonary position. METHODS: From 1999 to 2016, 82 children
      underwent 87 right ventricle to pulmonary artery conduit replacements (60
      Contegra(r) and 27 homografts). Demographics, operative and clinical data were
      obtained through a retrospective review of the medical records. The two groups
      were matched for comparison using propensity score matching. All the procedures
      were performed by the same team of surgeons. RESULTS: No statistically
      significant difference was observed between the two groups when considering the
      operative data for anesthesia, surgery, cardiopulmonary bypass and aortic
      clamping durations. A peroperative complication rate of 13.47% and 15.36% in
      Contegra(r) and homograft replacement groups respectively (p value = 0.758) was
      observed. There was no difference regarding the blood loss and fluid input. No
      statistically significant difference was observed between the two groups for the
      post-operative morbidity. We considered the Pediatric Risk of Mortality (PRISM)
      score, the day of extubation, the day of withdrawal of inotropic drugs, the
      length of the intensive care unit stay and the length of hospital stay. The
      overall mortality is 2.3% but there is no statistically significant difference
      between the two groups. CONCLUSION: Right ventricle to pulmonary artery conduit
      replacement procedure can be achieved with a low surgical morbidity or mortality,
      not influenced by the type of conduit that is replaced. Therefore, the choice
      between homograft or Contegra(r) for right ventricle to pulmonary artery
      reconstruction should not be influenced by the future surgical risk during the
      replacement procedure. TRIAL REGISTRATION: NCT03048071 . Registered 9 February
      2017 (retrospectively registered).

PMID- 29343298
TI  - Circular RNAs: biogenesis, expression and their potential roles in reproduction.
AB  - Unlike other non-coding RNAs (ncRNAs), circular RNA (circRNA) is generally
      presented as a covalently linked circle lacking both a 5' cap and a 3' tail.
      circRNAs were thought to be spliced intermediates, byproducts, or products of
      abnormal RNA splicing events. However, the high-throughput sequencing technology
      coupled with bioinformatics has recently uncovered thousands of endogenous
      circRNAs in cells of many different species. These circRNAs show various
      features, such as abundant expression, evolutionary conservation, cell- or tissue
      specific expression, and a higher resistance to degradation caused by exonuclease
      or ribonuclease (RNase), suggesting their potentially biological significance.
      However, the function of these circRNAs, their mechanism of action, and the
      regulation of their biogenesis and degradation remains largely unclear. The
      current research and findings of circRNA in the context of reproduction will be
      reviewed. Additionally, the perspectives of circRNAs in the field will be
      discussed.

PMID- 29343299
TI  - Atypical phenotypic aspects of autoimmune thyroid disorders in young patients
      with Turner syndrome.
AB  - : Aim of this commentary is to analyze the current views about the phenotypic
      features of Hashimoto's thyroiditis (HT) and Graves' disease (GD) in Turner
      syndrome (TS) girls, in terms of epidemiology, clinical and biochemical
      presentation, long-term course and metamorphic autoimmunity evolution. In TS GD
      course is not atypical, whereas HT course is characterized by both a mild
      presenting picture and a severe long-term evolution of thyroid function tests.
      Furthermore, TS girls seem to have an increased risk of switching over time from
      HT to GD. On the light of these findings, it may be concluded that TS girls with
      HT need a careful monitoring of thyroid status over time. CONCLUSIONS: 1) In
      children the association with TS is able to condition a peculiar phenotypic
      expression of HT in terms of epidemiology, presentation course and long-term
      metamorphic autoimmunity; 2) by contrast, children with TS do not exhibit an
      atypical clinical and biochemical course of GD, but only a significantly higher
      prevalence of this disease.

PMID- 29343300
TI  - Association between sickle cell and beta-thalassemia genes and hemoglobin
      concentration and anemia in children and non-pregnant women in Sierra Leone:
      ancillary analysis of data from Sierra Leone's 2013 National Micronutrient
      Survey.
AB  - OBJECTIVE: By measuring the associations between the presence of sickle cell and
      beta-thalassemia genes, we assessed the extent to which these hemoglobinopathies
      contribute to the high prevalence of anemia observed in preschool-aged children
      and women of reproductive age in Sierra Leone. RESULTS: The prevalence of anemia
      was statistically significantly higher in children with homozygous sickle cell
      genes (HbSS) than in children with normal hemoglobin genes (HbAA or HbAC), but
      there was no difference in anemia prevalence in those with heterozygous sickle
      cell trait (HbAS or HbSC) compared with those with normal hemoglobin genes. In
      women, there was no difference in anemia prevalence by sickle cell status. In
      both children and women, there was no difference in the anemia prevalence for
      individuals with or without the beta-thalassemia gene. For both sickle cell and
      beta-thalassemia, there was no significant difference in hemoglobin
      concentrations by sickle cell or beta-thalassemia status. Anemia prevalence was
      higher in children and women with homozygous sickle cell (HbSS). However, as the
      prevalence of HbSS children (5.4%) and women (1.6%) was quite small, it is
      unlikely that these hemoglobinopathies substantially contributed to the high
      anemia prevalence found in the 2013 national micronutrient survey.

PMID- 29343301
TI  - Circulating PCSK9 levels and 2-hPG are positively correlated in metabolic
      diseases in a Chinese Han population.
AB  - BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9), which plays a
      crucial role in lipoprotein metabolism, has been also regarded as an important
      marker for atherosclerosis. Available evidence indicated that 2-h postchallenge
      plasma glucose (2-hPG) could be another biomarker for atherosclerosis. However,
      currently the association between circulating PCSK9 and 2-hPG remains unclear.
      Here, we explored this potential link in a Chinese Han population. METHODS:
      Totally, 600 Chinese Han subjects from Nanjing district, China, were enrolled for
      the 75-g oral glucose tolerance test (OGTT), and they included normal glucose
      tolerance (NGT, n = 200), impaired glucose regulation (IGR, n = 200), and type 2
      diabetes (T2DM, n = 200). Anthropometric and biochemical determinations such as
      serum lipid measurements were made. A sandwich ELISA assay was performed to
      measure serum PCSK9 levels in all subjects. RESULTS: Serum PCSK9 concentrations
      were higher in IGR group (77.63 +/- 28.14 ng/ml) and T2DM group (90.62 +/- 39.96
      ng/ml) than in NGT group (65.33 +/- 32.68 ng/ml), and it was significantly higher
      in T2DM group than in IGR group (p < 0.01). Serum PCSK9 levels positively
      correlated with 2-hPG and LDL-C in all subgroups, but presented a positive
      correlation with fasting blood glucose (FBG) only in T2DM group. Using multiple
      regression model analysis, we also found that PCSK9 levels closely correlated
      with 2-hPG in all tested groups. According to multinomial logistic regression
      analysis, PCSK9 levels positively correlated with T2DM (OR = 1.017[1.010-1.025],
      p < 0.001) even after adjustment for lipid levels. Moreover, in subjects with
      normal FBG level, 2-hPG gradually and significantly increased across PCSK9
      tertiles (6.68 +/- 2.01, 7.48 +/- 2.10 and 8.27 +/- 2.41 mmol/L, respectively, p
      < 0.01); however, in subjects with normal 2-hPG levels, no such difference was
      observed. CONCLUSIONS: PCSK9 levels increase as glucose metabolism deteriorated.
      Serum PCSK9 levels positively correlated with 2-hPG in patients with metabolic
      diseases.

PMID- 29343302
TI  - Does previous abdominal surgery adversely affect perioperative and oncologic
      outcomes of laparoscopic radical cystectomy?
AB  - BACKGROUND: Laparoscopic radical cystectomy (LRC) has been shown to have less
      estimated blood loss (EBL), transfusion rate, narcotic analgesic requirement,
      earlier return of bowel function, and shorter hospital stay. The aim of this
      study was to investigate the feasibility, peri-operative and oncologic outcomes
      of laparoscopic radical cystectomy (LRC) in patients with previous abdominal
      surgery (PAS). METHODS: We retrospectively reviewed 243 patients undergoing open
      radical cystectomy (ORC) or LRC with bilateral pelvic lymph node dissection and
      urinary diversion or cutaneous ureterostomy at a single center from January 2010
      to December 2015. Demographic parameters, intra-operative variables, peri
      operative records, pathologic outcomes, and complication rate were reviewed to
      assess the impact of PAS on peri-operative and oncologic outcomes. RESULTS:
      Patients in both ORC and LRC subgroups were homogeneous in terms of demography
      characteristics including age, gender, BMI, ASA score, and comorbidity. Estimated
      blood loss (EBL) was higher in patients with PAS undergoing ORC compared to those
      with no PAS (P = 0.008). However, there was no significant difference of EBL
      among patients undergoing LRC with or without PAS (P = 0.896). There was no
      statistical difference in peri-operative parameters and pathological outcomes.
      Patients with PAS undergoing ORC and ileal conduit had a higher vascular injury
      rate (P = 0.017). Comparing patients with PAS performed by LRC and ORC, the
      number of patients with the vascular injury was higher in ORC groups regardless
      of the type of diversion (ileal conduit, P = 0.001, cutaneous ureterostomy, P =
      0.025). There is no significant difference in other complications. CONCLUSION:
      The presence of adhesions from PAS is not a contraindication to LRC. Patients
      with PAS may benefit from LRC with lower estimated blood loss, fewer transfusion
      rates, and vascular injuries. Furthermore, the overall oncologic outcomes and
      complication rate are similar between LRC and ORC patients with PAS.

PMID- 29343303
TI  - Comparison of modified wet suction technique and dry suction technique in
      endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for solid lesions:
      study protocol for a randomized controlled trial.
AB  - BACKGROUND: Several suction techniques have been developed recently to enhance
      tissue acquisition when sampling solid lesions using endoscopic ultrasound-guided
      fine-needle aspiration (EUS-FNA). The aim of this study is to determine whether a
      new modified wet suction technique (MWST) compared with the conventional dry
      suction technique (DRST) shall present better outcomes with respect to diagnostic
      yield and specimen quality of solid lesions in the intra-abdomen and mediastinum.
      METHODS/DESIGN: This is a single-blind, randomized, controlled, superiority trial
      conducted at four large tertiary care centers in China. Two hundred and ninety
      six patients with solid lesions referred for EUS-FNA will be randomly assigned to
      group A, using DRST for the first pass, or group B, using MWST for the first pass
      in a ratio of 1:1. Following a 2 * 2 cross-over design, the pass sequence for
      group A is DRST, MWST, DRST, MWST. For group B, the pass sequence is MWST, DRST,
      MWST, DRST. All procedures will be performed by experienced echoendoscopists, and
      the patients and assessors (cytologists and pathologists) will be blinded during
      the entire study. The primary outcome measure is the diagnosis yield. Secondary
      outcome measures are specimen quality, including assessment of quantity of cell,
      tissue integrity, and blood contamination. DISCUSSION: To our knowledge, this is
      the first large-scale randomized controlled trial to compare MWST with DRST when
      sampling solid lesions in the intra-abdomen and mediastinum. The results may
      contribute to future multicenter clinical trials in standardizing suction
      techniques during EUS-FNA. TRIAL REGISTRATION: Clinical Trials.gov, NCT02789371 .
      Retrospectively registered on 6 June 2016.

PMID- 29343304
TI  - Increasing incidence of Dirofilaria immitis in dogs in USA with focus on the
      southeast region 2013-2016.
AB  - BACKGROUND: A recent American Heartworm Society (AHS) survey on the incidence of
      adult heartworm infections in dogs in the United States of America showed a 21.7%
      increase in the average cases per veterinary clinic from 2013 to 2016. The
      analysis reported here was performed to see if heartworm testing results
      available via the Companion Animal Parasite Council (CAPC) aligned with the AHS
      survey and whether changes in heartworm preventive dispensing accounts for the
      increased incidence. The resistance of Dirofilaria immitis to macrocyclic
      lactones (MLs) has been previously reported. METHODS: An analysis of 7-9 million
      heartworm antigen tests reported annually to the Companion Animal Parasite
      Council (CAPC) from 2013 to 2016 was conducted and compared to the 2016 AHS
      survey. A state-by-state analysis across the southeastern USA was also performed.
      National heartworm preventive dispensing data were obtained from Vetstreet LLC
      and analyzed. All oral, topical and injectable heartworm preventives were
      included in this analysis, with injectable moxidectin counting as six doses.
      RESULTS: Positive antigen tests increased by 15.28% from 2013 to 2016, similar to
      the 21.7% increase reported by the AHS survey. Incidence in the southeastern USA
      increased by17.9% while the rest of USA incidence increased by 11.4%. State-by
      state analysis across the southeastern USA revealed an increased positive test
      frequency greater than 10% in 9 of 12 states evaluated. During this time, the
      overall proportion of dogs receiving heartworm prophylaxis remained relatively
      unchanged. Approximately 2/3 of the dogs in the USA received no heartworm
      prevention each year. CONCLUSION: These CAPC data show the rate of positive
      heartworm tests increasing significantly (P <  0.0001) in the USA from 2013 to
      2016, with a higher rate of increase in the southeastern USA than nationally.
      Only 1/3 of dogs in the USA were dispensed one or more doses of heartworm
      prevention annually by veterinarians, averaging 8.6 monthly doses/year.
      Veterinarians and pet owners should work together to follow CAPC and AHS
      guidelines to protect dogs from infection with D. immitis. Lack of preventive use
      and the emergence of heartworm resistance to MLs could both be impacting the
      increased rate of positive heartworm tests in dogs.

PMID- 29343305
TI  - Relationship between Eustachian tube dysfunction and otitis media with effusion
      in radiotherapy patients.
AB  - OBJECTIVE: This study evaluated the relationship between radiation and Eustachian
      tube dysfunction, and examined the radiation dose required to induce otitis media
      with effusion. METHODS: The function of 36 Eustachian tubes in 18 patients with
      head and neck cancer were examined sonotubometrically before, during, and 1, 2
      and 3 months after, intensity-modulated radiotherapy. Patients with an increase
      of 5 dB or less in sound pressure level (dB) during swallowing were categorised
      as being in the dysfunction group. Additionally, radiation dose distributions
      were assessed in all Eustachian tubes using three dose-volume histogram
      parameters. RESULTS: Twenty-two of 25 normally functioning Eustachian tubes
      before radiotherapy (88.0 per cent) shifted to the dysfunction group after
      therapy. All ears that developed otitis media with effusion belonged to the
      dysfunction group. The radiation dose threshold evaluation revealed that ears
      with otitis media with effusion received significantly higher doses to the
      Eustachian tubes. CONCLUSION: The results indicate a relationship between
      radiation dose and Eustachian tube dysfunction and otitis media with effusion.

PMID- 29343307
TI  - INFORMED CHOICE AND FEMALE STERILIZATION IN SOUTH ASIA AND LATIN AMERICA.
AB  - Globally, female sterilization is one of the most popular contraceptive methods
      despite concerns about quality of care for women who report being sterilized. In
      this study, informed choice among sterilized women was quantified using
      Demographic and Health Survey (DHS) data from 2000 to 2012 for countries in South
      Asia and Latin America. Three responses measured informed choice and knowledge
      about whether women were informed by a health worker or provider: that
      sterilization is permanent, the potential side-effects of sterilization and other
      methods of contraception. An ascending composite Method Information Index with
      scores ranging from 0 (women received no information) to 3 (women received
      information across all three indicators) was used. Using ordinal logistic
      regression analysis, the results indicated that women younger than 25 and older
      than 35 at the time of sterilization, and those at high parities, had lower odds
      of a high score on the index, while the opposite was true for women sterilized in
      the private sector in Latin America. Educated women in India had higher odds of a
      high score on the index, while the same was true for educated and wealthy women
      in Colombia. These findings indicate that not enough health care providers spend
      time informing women in South Asia and Latin America about different aspects of
      sterilization, and that there are specific groups of women that are more
      affected. There is an urgent need to improve quality of care within health
      systems providing sterilization for this very important and effective type of
      contraception.

PMID- 29343306
TI  - Nasal changes associated with exercise in athletes: systematic review.
AB  - BACKGROUND: The prevalence of rhinitis in athletes has frequently been studied in
      combination with asthma, but the impact of exercise on the paracrine and
      secretory functions of nasal mucosa is less well established. This systematic
      review aimed to examine the effect of exercise on nasal mucosa in elite athletes.
      METHOD: A systematic search of Medline, Embase and the non-Medline subset of
      PubMed, from inception to 8th March 2016, was performed to identify studies on
      rhinitis in athletes. RESULTS: Of the 373 identified unique articles, a total of
      8 studies satisfied the criteria for this review. CONCLUSION: There is no
      evidence in the existing literature that indicates a reduction in nasal airway
      induced by exercise. Olfaction and mucociliary transport time are affected in
      swimmers, which can likely be attributed to chlorine irritation and which
      resolves with training cessation. Short-term strenuous exercise may trigger
      changes in cytology and prolonged mucociliary transport time, which also resolve
      quickly with rest.

PMID- 29343308
TI  - Invited review: Genomic selection for small ruminants in developed countries: how
      applicable for the rest of the world?
AB  - Improved management and use of estimated breeding values in breeding programmes,
      have resulted in rapid genetic progress for small ruminants (SR) in Europe and
      other developed countries. The development of single nucleotide polymorphisms
      chips opened opportunities for genomic selection (GS) in SR in these countries.
      Initially focused on production traits (growth and milk), GS has been extended to
      functional traits (reproductive performance, disease resistance and meat
      quality). The GS systems have been characterized by smaller reference populations
      compared with those of dairy cattle and consisting mostly of cross- or multi
      breed populations. Molecular information has resulted in gains in accuracy of
      between 0.05 and 0.27 and proved useful in parentage verification and the
      identification of QTLs for economically important traits. Except for a few
      established breeds with some degree of infrastructure, the basic building blocks
      to support conventional breeding programmes in small holder systems are lacking
      in most developing countries. In these systems, molecular data could offer quick
      wins in undertaking parentage verification and genetic evaluations using G
      matrix, and determination of breed composition. The development of next
      generation molecular tools has prompted investigations on genome-wide signatures
      of selection for mainly adaptive and reproduction traits in SR in developing
      countries. Here, the relevance of the developments and application of GS and
      other molecular tools in developed countries to developing countries context is
      examined. Worth noting is that in the latter, the application of GS in SR will
      not be a 'one-size fits all' scenario. For breeds with some degree of
      conventional genetic improvement, classical GS may be feasible. In small holder
      systems, where production is key, community-based breeding programmes can provide
      the framework to implement GS. However, in fragile growth systems, for example
      those found in marginal environments, innovative GS to maximize adaptive
      diversity will be required. A cost-benefit analysis should accompany any strategy
      of implementing GS in these systems.

PMID- 29343309
TI  - Could seasonal allergy be a risk factor for acute rhinosinusitis in children?
AB  - OBJECTIVE: To evaluate the incidence of acute rhinosinusitis in children with
      grass pollen induced rhinitis during the period of grass pollinosis. METHODS:
      Children with nasal symptoms from grass pollen induced rhinitis but without
      rhinosinusitis symptoms were selected. Their parents were asked to complete a
      diary during pollen exposure to report nasal symptoms and drugs used daily. When
      rhinosinusitis was suspected, the confirmatory diagnosis of acute rhinosinusitis
      was made by fibro-endoscopy. Children without inhalant allergy served as
      controls. RESULTS: Seventeen out of 242 children (7.0 per cent) had a diagnosis
      of acute rhinosinusitis, confirmed by fibro-endoscopy, during grass pollination,
      compared to 3 out of 65 (4.6 per cent) in the control group (p = 0.49). Among
      allergic children, those with acute rhinosinusitis had symptoms for a greater
      number of days and/or a higher symptoms score than children without acute
      rhinosinusitis. CONCLUSION: Children with grass pollen induced rhinitis during
      exposure to pollen have an incidence of endoscopically confirmed acute
      rhinosinusitis comparable to non-allergic children. This suggests that grass
      pollen induced rhinitis is a negligible risk factor for acute rhinosinusitis.

PMID- 29343310
TI  - Effect of dietary fish oil on selected inflammatory markers in pigs.
AB  - The present study tested a hypothesis that dietary fish oil (eicosapentaenoic
      acid+docosahexaenoic acid) in a commonly achievable dose ameliorates a systemic
      inflammation in pigs. Two groups of pigs of 16 animals each were fed a diet with
      either 2.5% of fish oil (F) or a control diet with 2.5% of palm oil (P). After 70
      days of fattening, eight F and eight P pigs were challenged (F+; P+) i.v. by
      lipopolysaccharide. After 3 h, all pigs were sacrificed and blood, liver and
      visceral adipose tissue (VAT) samples were taken. No significant effect (P>0.05)
      of dietary oil on the feed intake and daily weight gain was found out. Less
      neutrophils (16.8% v. 28.8%; P0.05) between F+ and P+ pigs in the peroxisome
      proliferator-activated receptor gamma, GPR120, Adipor1 and Adipor2 (adiponectin
      receptor) gene expression, respectively, was established; plasma adiponectin was
      the same (21.1 ng/ml) in F+ and P+ pigs. In comparison with the P+ pigs,
      increased expression of the lipopolysaccharide-binding protein (LBP) gene and
      intercellular adhesion molecule 1 (ICAM1) gene was found out in the liver of the
      F+ pigs; expression of the tumor necrosis factor alpha (TNFalpha) gene was higher
      in the liver but lower in the VAT of the F+ pigs (P<0.05). The F+ pigs had higher
      (P<0.05) plasma concentration of both anti-inflammatory cytokine interleukin-4
      (0.46 v. 0.04 ng/ml) and pro-inflammatory TNF-alpha (13.41 v. 7.72 ng/ml). It was
      concluded that dietary fish oil at the tested amount had a negligible effect on
      expression of the evaluated receptor genes and plasma adiponectin, and had an
      ambiguous effect on expression of cytokine genes and plasma cytokine levels.

PMID- 29343311
TI  - Decompensated labyrinthine weakness presenting as de novo peripheral vertigo: a
      discrete clinical entity?
AB  - OBJECTIVE: A distinct subgroup of patients, presenting with apparently
      spontaneous onset of vertigo, is described. RESULTS: Although vestibular
      evaluation revealed caloric weakness, the proximate cause of vertigo was not
      labyrinthine dysfunction, but rather the loss of vestibular compensation for an
      older and previously compensated labyrinthine injury. CONCLUSION: Instead of
      addressing the vestibular weakness, effective management needs to focus on the
      condition that has caused the loss of compensation.

PMID- 29343312
TI  - Fecal Microbiota Transplant for Multidrug-Resistant Organism Decolonization
      Administered During Septic Shock.

PMID- 29343313
TI  - Eucalyptus leaves powder, antibiotic and probiotic addition to broiler diets:
      effect on growth performance, immune response, blood components and carcass
      traits.
AB  - The study was conducted to investigate the effects of different levels of
      eucalyptus powder (EP), virginiamycin and probiotic on performance, immunity,
      blood components and carcass traits of broiler chickens. A total of 250, 1-day
      old male broiler chickens (Ross 308) were randomly allocated to five treatments
      with five replicates and 10 chicks each, as a completely randomized design. The
      dietary treatments consisted of: basal diet (BD), BD+0.25% EP, BD+0.5% EP,
      BD+0.01% of diet probiotic (Protexin), BD+0.02% of diet antibiotic
      (virginiamycin). Dietary supplementation did not affect feed intake, BW gain
      (BWG) and feed conversion ratio (FCR) during starter and grower phases, but BWG
      and FCR were affected during the finisher and whole periods (P<0.05).The highest
      BWG and lowest FCR were obtained in birds fed with virginiamycin and 0.5% EP.
      Dietary supplementation significantly increased the relative weight of carcass
      and breast (P<0.05). Treatments had no effect on relative weights of internal
      organs and small intestine except for bursa that increased by treatments.
      Relative length of jejunum also increased by treatments (P<0.05). Antibody
      production against sheep red blood cells did not changed in primary titer (day
      35), but it significantly increased in secondary titer (day 42) by 0.5% EP. White
      blood cell counts were increased and cholesterol decreased by dietary
      supplementation (P<0.05). In conclusion, the results of this study showed that
      0.5% EP served as a useful replacement for antibiotic and would improve
      performance and immune response of broiler chickens.

PMID- 29343314
TI  - Cell-free DNA: the role in pathophysiology and as a biomarker in kidney diseases.
AB  - Cell-free DNA (cfDNA) is present in various body fluids and originates mostly
      from blood cells. In specific conditions, circulating cfDNA might be derived from
      tumours, donor organs after transplantation or from the foetus during pregnancy.
      The analysis of cfDNA is mainly used for genetic analyses of the source tissue 
      tumour, foetus or for the early detection of graft rejection. It might serve also
      as a nonspecific biomarker of tissue damage in critical care medicine. In kidney
      diseases, cfDNA increases during haemodialysis and indicates cell damage. In
      patients with renal cell carcinoma, cfDNA in plasma and its integrity is studied
      for monitoring of tumour growth, the effects of chemotherapy and for prognosis.
      Urinary cfDNA is highly fragmented, but the technical hurdles can now be overcome
      and urinary cfDNA is being evaluated as a potential biomarker of renal injury and
      urinary tract tumours. Beyond its diagnostic application, cfDNA might also be
      involved in the pathogenesis of diseases affecting the kidneys as shown for
      systemic lupus, sepsis and some pregnancy-related pathologies. Recent data
      suggest that increased cfDNA is associated with acute kidney injury. In this
      review, we discuss the biological characteristics, sources of cfDNA, its
      potential use as a biomarker as well as its role in the pathogenesis of renal and
      urinary diseases.

PMID- 29343315
TI  - Subclinical inflammation affects iron and vitamin A but not zinc status
      assessment in Senegalese children and Cambodian children and women.
AB  - OBJECTIVE: To assess the impact of the acute-phase response (APR) during
      inflammation on Fe, Zn and vitamin A biomarkers to allow accurate evaluation of
      micronutrient status in populations. DESIGN: Ferritin (FER), soluble transferrin
      receptor (TfR), retinol-binding protein (RBP), Zn, alpha1-acid glycoprotein and C
      reactive protein concentrations were measured. Correction factors (CF) for each
      biomarker were calculated as the ratio for groups at different stages of
      inflammation v. the reference group without
      inflammation.Setting/SubjectsSenegalese (n 594) and Cambodian schoolchildren (n
      2471); Cambodian women of reproductive age (n 2117). RESULTS: TfR was higher
      during the incubation phase (CF=1.17) and lower during early and late
      convalescence (CF=0.87 and 0.78). FER was higher during all phases (CF=0.83, 0.48
      and 0.65, respectively). RBP was higher during incubation (CF=0.88) and lower
      during early convalescence (CF=1.21). No effect of inflammation on Zn status was
      found. CONCLUSIONS: Inflammation led to overestimation of Fe status and
      underestimation of vitamin A status. The response of the biomarker for vitamin A
      status to inflammation depended on the vitamin A status of the populations.
      Surprisingly, the assessment of Zn status was hardly affected by inflammation.
      Different phases of the APR had opposite effects on the assessment of Fe status
      using TfR. More research is needed to define the correct methods to adjust for
      inflammation in nutritional studies.

PMID- 29343316
TI  - Black soldier fly larva fat inclusion in finisher broiler chicken diet as an
      alternative fat source.
AB  - The objective of the present study was to evaluate the effects of partial or
      total replacement of finisher diet soybean oil with black soldier fly (Hermethia
      illucens L.; HI) larva fat on the growth performance, carcass traits, blood
      parameters, intestinal morphology and histological features of broiler chickens.
      At 21 days of age, a total of 120 male broiler chickens (Ross 308) were randomly
      allocated to three experimental groups (five replicates and eight birds/pen). To
      a basal control diet (C; 68.7 g/kg as fed of soybean oil), either 50% or 100% of
      the soybean oil was replaced with HI larva fat (HI50 and HI100 group,
      respectively). Growth performance was evaluated throughout the trial. At day 48,
      15 birds (three birds/pen) per group were slaughtered at a commercial abattoir.
      Carcass yield and proportions of carcass elements were recorded. Blood samples
      were taken from each slaughtered chicken for haematochemical index determination.
      Morphometric analyses were performed on the duodenum, jejunum and ileum. Samples
      of liver, spleen, thymus, bursa of fabricius, kidney and heart were submitted to
      histological investigations. Growth performance, carcass traits, haematochemical
      parameters and gut morphometric indexes were not influenced by the dietary
      inclusion of HI larva fat. Histopathological alterations developed in the spleen,
      thymus, bursa of fabricius and liver and were identified in all of the
      experimental groups, but HI larva fat inclusion did not significantly affect
      (P>0.05) the severity of the histopathological findings. The present study
      suggests that 50% or 100% replacement of soybean oil with HI larva fat in broiler
      chickens diets has no adverse effects on growth performance or blood parameters
      and had no beneficial effect on gut health.

PMID- 29343317
TI  - Disaster-Relief Fraud: A Dark Side of Disasters.

PMID- 29343407
TI  - A Flat Pink Plaque On The Right Anterior Forearm.

PMID- 29343408
TI  - Response to 'Perilesional edema in brain cancer: Independent prognosticator or
      epiphenomenon of biomolecular signature?'

PMID- 29343409
TI  - Monitoring early changes in rectal tumor morphology and volume during 5 weeks of
      preoperative chemoradiotherapy - An evaluation with sequential MRIs.
AB  - PURPOSE: To assess early changes in rectal tumor volume and morphology on
      sequential MRIs performed during 5 weeks of chemoradiotherapy. MATERIALS AND
      METHODS: Thirteen patients underwent weekly T2W-MRI during 5 weeks of
      preoperative radiotherapy (total 50 Gy), starting after the first week of
      radiation. Two radiologists visually evaluated tumor volume and morphology and
      one reader manually segmented tumors for each time point to quantitatively
      calculate tumor volumes. Evolution in tumor volume/morphology was assessed over
      time and compared between good responders (tumor regression grade (TRG) 1-2) and
      poor responders (TRG 3-5). RESULTS: Tumor volumes decreased significantly during
      radiation. Early signs of response were also visually apparent: in the majority
      of good responders an early fibrotic transformation (week 2-3) as well as a
      visually estimated early volume reduction of >1/3 (week 1-2), was observed while
      these early changes only occurred in a minority of poor responders. CONCLUSION:
      Results of this exploratory pilot study suggest that changes in rectal tumor
      morphology (fibrosis) and volume can already be observed early during radiation,
      both when measured quantitatively and when assessed visually. These changes
      appear to be indicative of the final treatment outcome.

PMID- 29343410
TI  - Random uncertainty of photometric determination of hemolysis index on the Abbott
      Architect c16000 platform.
AB  - BACKGROUND: Automatic photometric determination of the hemolysis index (HI) on
      serum and plasma samples is central to detect potential interferences of in vitro
      hemolysis on laboratory tests. When HI is above an established cut-off for
      interference, results may suffer from a significant bias and undermine clinical
      reliability of the test. Despite its undeniable importance for patient safety,
      the analytical performance of HI estimation is not usually checked in
      laboratories. Here we evaluated for the first time the random source of
      measurement uncertainty of HI determination on the two Abbott Architect c16000
      platforms in use in our laboratory. METHODS: From January 2016 to September 2017,
      we collected data from daily photometric determination of HI on a fresh-frozen
      serum pool with a predetermined HI value of ~100 (corresponding to ~1g/L of free
      hemoglobin). Monthly and cumulative CVs were calculated. RESULTS: During
      21months, 442 and 451 measurements were performed on the two platforms,
      respectively. Monthly CVs ranged from 0.7% to 2.7% on c16000-1 and from 0.8% to
      2.5% on c16000-2, with a between-platform cumulative CV of 1.82% (corresponding
      to an expanded uncertainty of 3.64%). Mean HI values on the two platforms were
      just slightly biased (101.3 vs. 103.1, 1.76%), but, due to the high precision of
      measurements, this difference assumed statistical significance (p<0.0001).
      CONCLUSIONS: Even though no quality specifications are available to date, our
      study shows that the HI measurement on Architect c16000 platform has nice
      reproducibility that could be considered in establishing the state of the art of
      the measurement.

PMID- 29343411
TI  - Consequence of enhanced LC3-trafficking for a live, attenuated M. tuberculosis
      vaccine.
AB  - Development of a new vaccine against tuberculosis is urgently needed. Recent work
      has demonstrated that two related LC3-associated trafficking pathways, autophagy
      and LC3-associated phagocytosis (LAP), enhance antigen presentation and might
      play a role in vaccine efficacy. Mycobacterium tuberculosis inhibits both LC3
      trafficking pathways. Moreover, the vaccine strain, BCG, induces even less LC3
      trafficking than M. tuberculosis, which may help explain its limited efficacy. To
      determine whether enhanced LC3-trafficking can improve efficacy of a live,
      attenuated M. tuberculosis vaccine, we took advantage of our recent finding that
      the bacterial virulence factor CpsA inhibits LAP. When we deleted cpsA in the
      mc26206 vaccine strain, it dramatically increased LC3-trafficking. We compared
      the protective efficacy of the strain lacking cpsA to the parent strain and to
      BCG in mice challenged with M. tuberculosis. We found that the strain lacking
      cpsA generated modestly enhanced protection in the spleen, but overall did not
      outperform BCG.

PMID- 29343413
TI  - Exposure to and colonisation by antibiotic-resistant E. coli in UK coastal water
      users: Environmental surveillance, exposure assessment, and epidemiological study
      (Beach Bum Survey).
AB  - BACKGROUND: Antibiotic-resistant bacteria (ARB) present a global public health
      problem. With numbers of community-acquired resistant infections increasing,
      understanding the mechanisms by which people are exposed to and colonised by ARB
      can help inform effective strategies to prevent their spread. The role natural
      environments play in this is poorly understood. This is the first study to
      combine surveillance of ARB in bathing waters, human exposure estimates and
      association between exposure and colonisation by ARB in water users. METHODS: 97
      bathing water samples from England and Wales were analysed for the proportion of
      E. coli harbouring blaCTX-M. These data were used to estimate the likelihood of
      water users ingesting blaCTX-M-bearing E. coli. Having identified surfers as
      being at risk of exposure to ARB, a cross-sectional study was conducted. Regular
      surfers and non-surfers were recruited to assess whether there is an association
      between surfing and gut colonisation by blaCTX-M-bearing E. coli. RESULTS: 11 of
      97 bathing waters sampled were found to contain blaCTX-M-bearing E. coli. While
      the percentage of blaCTX-M-bearing E. coli in bathing waters was low (0.07%),
      water users are at risk of ingesting these ARB. It is estimated that over 2.5
      million water sports sessions occurred in 2015 resulting in the ingestion of at
      least one blaCTX-M-bearing E. coli. In the epidemiological survey, 9/143 (6.3%)
      surfers were colonised by blaCTX-M-bearing E. coli, as compared to 2/130 (1.5%)
      of non-surfers (risk ratio=4.09, 95% CI 1.02 to 16.4, p=0.046). CONCLUSIONS:
      Surfers are at risk of exposure to and colonisation by clinically important
      antibiotic-resistant E. coli in coastal waters. Further research must be done on
      the role natural environments play in the transmission of ARB.

PMID- 29343414
TI  - Oxaliplatin and neuropathy: A role for sodium channels.

PMID- 29343412
TI  - Implementing genome-driven personalized cardiology in clinical practice.
AB  - Genomics designates the coordinated investigation of a large number of genes in
      the context of a biological process or disease. It may be long before we attain
      comprehensive understanding of the genomics of common complex cardiovascular
      diseases (CVDs) such as inherited cardiomyopathies, valvular diseases, primary
      arrhythmogenic conditions, congenital heart syndromes, hypercholesterolemia and
      atherosclerotic heart disease, hypertensive syndromes, and heart failure with
      preserved/reduced ejection fraction. Nonetheless, as genomics is evolving
      rapidly, it is constructive to survey now pertinent concepts and breakthroughs.
      Today, clinical multimodal electronic medical/health records (EMRs/EHRs)
      incorporating genomic information establish a continuously-learning, vast
      knowledge-network with seamless cycling between clinical application and
      research. It can inform insights into specific pathogenetic pathways, guide
      biomarker-assisted precise diagnoses and individualized treatments, and stratify
      prognoses. Complex CVDs blend multiple interacting genomic variants, epigenetics,
      and environmental risk-factors, engendering progressions of multifaceted disease
      manifestations, including clinical symptoms and signs. There is no straight-line
      linkage between genetic cause(s) or causal gene-variant(s) and disease
      phenotype(s). Because of interactions involving modifier-gene influences, (micro)
      environmental, and epigenetic effects, the same variant may actually produce
      dissimilar abnormalities in different individuals. Implementing genome-driven
      personalized cardiology in clinical practice reveals that the study of CVDs at
      the level of molecules and cells can yield crucial clinical benefits.
      Complementing evidence-based medicine guidelines from large ("one-size fits all")
      randomized controlled trials, genomics-based personalized or precision cardiology
      is a most-creditable paradigm: It provides customizable approaches to prevent,
      diagnose, and manage CVDs with treatments directly/precisely aimed at causal
      defects identified by high-throughput genomic technologies. They encompass stem
      cell and gene therapies exploiting CRISPR-Cas9-gene-editing, and metabolomic
      pharmacogenomic therapeutic modalities, precisely fine-tuned for the individual
      patient. Following the Human Genome Project, many expected genomics technology to
      provide imminent solutions to intractable medical problems, including CVDs. This
      eagerness has reaped some disappointment that advances have not yet materialized
      to the degree anticipated. Undoubtedly, personalized genetic/genomics testing is
      an emergent technology that should not be applied without supplementary
      phenotypic/clinical information: Genotype?Phenotype. However, forthcoming
      advances in genomics will naturally build on prior attainments and, combined with
      insights into relevant epigenetics and environmental factors, can plausibly
      eradicate intractable CVDs, improving human health and well-being.

PMID- 29343415
TI  - Paradigms for restoration of somatosensory feedback via stimulation of the
      peripheral nervous system.
AB  - The somatosensory system contributes substantially to the integration of multiple
      sensor modalities into perception. Tactile sensations, proprioception and even
      temperature perception are integrated to perceive embodiment of our limbs. Damage
      of somatosensory networks can severely affect the execution of daily life
      activities. Peripheral injuries are optimally corrected via direct interfacing of
      the peripheral nerves. Recent advances in implantable devices, stimulation
      paradigms, and biomimetic sensors enabled the restoration of natural sensations
      after amputation of the limb. The refinement of stimulation patterns to deliver
      natural feedback that can be interpreted intuitively such to prescind from long
      learning sessions is crucial to function restoration. For this review, we
      collected state-of-the-art knowledge on the evolution of stimulation paradigms
      from single fiber stimulation to the eliciting of multisensory sensations. Data
      from the literature are structured into six sections: (a) physiology of the
      somatosensory system; (b) stimulation of single fibers; (c) restoral of
      multisensory percepts; (d) closure of the control loop in hand prostheses; (e)
      sensory restoration and the sense of embodiment, and (f) methodologies to assess
      stimulation outcomes. Full functional recovery demands further research on
      multisensory integration and brain plasticity, which will bring new paradigms for
      intuitive sensory feedback in the next generation of limb prostheses.

PMID- 29343416
TI  - Intrathecal tranexamic acid - an accident waiting to happen?

PMID- 29343417
TI  - Does the addition of active body warming to in-line intravenous fluid warming
      prevent maternal hypothermia during elective caesarean section? A randomised
      controlled trial.

PMID- 29343418
TI  - The combination of corticosteroid and tocolytic therapy in a preeclamptic patient
      is a risk factor for the development of acute pulmonary oedema.

PMID- 29343419
TI  - Successful use of non-invasive positive pressure ventilation in a patient with
      the severe form of X-linked myotubular myopathy.
AB  - The severity of X-linked myotubular myopathy (XLMTM) ranges from mild to severe,
      depending on the level of ventilatory support required. Patients with the severe
      form of XLMTM usually die within the first year of life due to respiratory
      failure. Most survivors need tracheostomies, and there has only been one report
      about the use of non-invasive positive pressure ventilation (NPPV) in patients
      with the severe form of XLMTM because of the severity of the associated
      respiratory failure. We successfully applied NPPV with high-span positive
      inspiratory pressure (PIP) in a patient with the severe form of XLMTM, who also
      had secondary pectus excavatum. About a year after the initiation of NPPV with
      high-span PIP, the patient's pectus excavatum had improved. As the patient's
      pectus excavatum improved, his respiratory disturbance was ameliorated, and the
      frequency of respiratory infections gradually decreased. NPPV might be the first
      choice respiratory management strategy for patients with XLMTM.

PMID- 29343421
TI  - Frequency of small-colony variants and antimicrobial susceptibility of
      methicillin-resistant Staphylococcus aureus in cystic fibrosis patients.
AB  - BACKGROUND: Small-colony variants (SCVs) are a distinct phenotype of
      Staphylococcus aureus, known for their role in chronic, difficult to treat
      infections, including cystic fibrosis (CF) lung disease. The goal of this study
      was to characterize SCV MRSA infection in an adult and pediatric CF population
      and to identify antibiotic susceptibility patterns unique to SCV MRSA. METHODS:
      We recovered methicillin-resistant S. aureus (MRSA) from respiratory culture
      samples from CF patients at the Johns Hopkins Hospital during a 6month study
      period. RESULTS: Of 1161 samples, 200 isolates (17%) were identified as MRSA, and
      37 isolates from 28 patients were identified as SCV MRSA. A higher proportion of
      MRSA was found among SCV isolates (37/66, 56%) compared to normal colony variant
      (NCV) isolates (163/417, 39%), p=0.02. All SCV MRSA isolates from individual
      patients were susceptible to vancomycin and ceftaroline, but they demonstrated
      higher rates of antibiotic resistance to trimethoprim/sulfamethoxazole,
      moxifloxacin, and erythromycin, compared to NCV MRSA isolates. Additionally,
      individuals with SCV MRSA had lower lung function, higher rates of persistent
      MRSA infection, and higher rates of previous antibiotic use, compared to
      individuals with NCV MRSA. CONCLUSIONS: A significant proportion of MRSA isolates
      recovered from patients with CF have the SCV morphology. Compared to individuals
      with NCV MRSA, those with SCV MRSA have higher rates of persistent MRSA infection
      and lower lung function. SCV MRSA isolates were more resistant than NCV, but they
      are highly susceptible to vancomycin, linezolid and ceftaroline.

PMID- 29343422
TI  - Effect of foetal and infant growth and body composition on respiratory outcomes
      in preterm-born children.
AB  - Body composition and growth outcomes of preterm-born subjects have been studied
      by many researchers. In general, preterm-born children have lower height and
      weight especially in infancy. Despite showing potential for catch-up growth, they
      continue to lag behind their term counterparts in adolescence and adulthood. The
      various methods of studying body composition and the differing gestations and
      ages at which it is assessed may go some way to explaining the inconsistent
      results observed in different studies. In addition, there is a paucity of data on
      the effects of foetal and infant growth and of body composition on later
      respiratory outcomes. In largely term-born subjects, foetal growth and growth
      trajectories appear to have differential effects on later respiratory outcomes.
      Early weight gain in infancy appears to be associated with increased respiratory
      symptoms in childhood but catch-up growth in infancy appears to be associated
      with possible improved lung function status.

PMID- 29343420
TI  - AMPK Re-Activation Suppresses Hepatic Steatosis but its Downregulation Does Not
      Promote Fatty Liver Development.
AB  - Nonalcoholic fatty liver disease is a highly prevalent component of disorders
      associated with disrupted energy homeostasis. Although dysregulation of the
      energy sensor AMP-activated protein kinase (AMPK) is viewed as a pathogenic
      factor in the development of fatty liver its role has not been directly
      demonstrated. Unexpectedly, we show here that liver-specific AMPK KO mice display
      normal hepatic lipid homeostasis and are not prone to fatty liver development,
      indicating that the decreases in AMPK activity associated with hepatic steatosis
      may be a consequence, rather than a cause, of changes in hepatic metabolism. In
      contrast, we found that pharmacological re-activation of downregulated AMPK in
      fatty liver is sufficient to normalize hepatic lipid content. Mechanistically,
      AMPK activation reduces hepatic triglyceride content both by inhibiting lipid
      synthesis and by stimulating fatty acid oxidation in an LKB1-dependent manner,
      through a transcription-independent mechanism. Furthermore, the effect of the
      antidiabetic drug metformin on lipogenesis inhibition and fatty acid oxidation
      stimulation was enhanced by combination treatment with small-molecule AMPK
      activators in primary hepatocytes from mice and humans. Overall, these results
      demonstrate that AMPK downregulation is not a triggering factor in fatty liver
      development but in contrast, establish the therapeutic impact of pharmacological
      AMPK re-activation in the treatment of fatty liver disease.

PMID- 29343423
TI  - Request for HIV serology in primary care: A survey of medical and nursing
      professionals.
AB  - INTRODUCTION: In the Community of Madrid there is 42.7% late HIV diagnosis.
      Primary care is the gateway to the health system and the frequency of serological
      tests requested by these professionals is unknown. The objectives were to
      establish the frequency of requests for HIV serology by medical and nursing
      primary care professionals in the Community of Madrid and the factors associated
      with these requests. METHOD: An 'on-line' survey was conducted, asking
      professionals who participated in the evaluation study of strategies to promote
      early diagnosis of HIV in primary care in the Community of Madrid (ESTVIH) about
      the number of HIV-serology tests requested in the last 12 months. The association
      between HIV-serology requesting and the sociodemographic and clinical practice
      characteristics of the professionals was quantified using adjusted odds ratios
      (aOR) according to logistic regression. RESULTS: 264 surveys (59.5% physicians).
      Eighty-two point two percent of medical and 18.7% of nursing professionals
      reported requesting at least one HIV-serology in the last 12 months (median: 15
      and 2 HIV-serology request, respectively). The doctors associated the request
      with: being male (aOR: 2.95; 95% CI: 0.82-10.56), being trained in pre-post HIV
      test counselling (aOR: 2.42; 95% CI: 0.84-6.93) and the nurses with: age (<50
      years; aOR: 2.75; 95% CI: 0.97-7.75), and number of years working in primary care
      (>13 years; aOR: 3.02; 95% CI: 1.07-8.52). CONCLUSION: It is necessary to promote
      HIV testing and training in pre-post HIV test counselling for medical and nursing
      professionals in primary care centres.

PMID- 29343425
TI  - Iba57p participates in maturation of a [2Fe-2S]-cluster Rieske protein and in
      formation of supercomplexes III/IV of Saccharomyces cerevisiae electron transport
      chain.
AB  - The [Fe-S] late-acting subsystem comprised of Isa1p/Isa2p, Grx5p, and Iba57p
      proteins (Fe-S-IBG subsystem) is involved in [4Fe-4S]-cluster protein assembly.
      The effect of deleting IBA57 in Saccharomyces cerevisiae on mitochondrial
      respiratory complex integration and functionality associated with Rieske protein
      maturation was evaluated. The iba57Delta mutant showed decreased expression and
      maturation of the Rieske protein. The loss of Rieske protein caused by IBA57
      deletion affected the structure of supercomplexes III2IV2 and III2IV1 and their
      integration into the mitochondria, causing dysfunction in the electron transport
      chain. These effects were correlated with decreased cytochrome functionality and
      content in the iba57Delta mutant. These findings suggest that Iba57p participates
      in maturation of the [2Fe-2S]-cluster into the Rieske protein and that Rieske
      protein plays important roles in the conformation and functionality of
      mitochondrial supercomplex III/IV in the electron transport chain.

PMID- 29343424
TI  - IGF1/MAPK/ERK signaling pathway-mediated programming alterations of adrenal
      cortex cell proliferation by prenatal caffeine exposure in male offspring rats.
AB  - Our previous study proposed a glucocorticoid-insulin-like growth factor 1 (GC
      IGF1) axis programming mechanism for prenatal caffeine exposure (PCE)-induced
      adrenal developmental dysfunction. Here, we focused on PCE-induced cell
      proliferation changes of the adrenal cortex in male offspring rats before and
      after birth and clarified the intrauterine programming mechanism. On gestational
      day (GD) 20, the PCE group had an elevated serum corticosterone level reduced
      fetal bodyweight, maximum adrenal sectional area, and elevated adrenal
      corticosterone and aldosterone contents. However, in postnatal week (PW) 6, the
      serum corticosterone level was decreased, and the bodyweight, with catch-up
      growth, adrenal cortex maximum cross-sectional area and aldosterone content were
      relatively increased, while the adrenal corticosterone content was lower. On
      GD20, the expression of adrenal IGF1, IGF1R and proliferating cell nuclear
      antigen (PCNA) were decreased, while the expression of these factors at PW6 were
      increased in the PCE group. Fetal adrenal gene chip analysis suggested that the
      mitogen-activated protein kinase/extracellular regulated protein kinase
      (MAPK/ERK) signal pathway was suppressed in the PCE group. Moreover, in the rat
      primary adrenal cells, corticosterone (rather than caffeine) was shown to
      significantly inhibit cell proliferation, IGF1 and PCNA expression, and ERK
      phosphorylation, which could be reversed by exogenous IGF1. Meanwhile, the
      effects of exogenous IGF1 were reversed by the ERK pathway inhibitor (PD184161).
      In conclusion, PCE could induce programming alterations in adrenal cortical cell
      proliferation before and after birth in male offspring rats. The underlying
      mechanism is associated with the inhibition of fetal adrenal IGF1-related
      MAPK/ERK signaling pathway caused by high glucocorticoid levels.

PMID- 29343426
TI  - Environmental Mycobacterium avium subsp. hominissuis have a higher probability to
      act as a recipient in conjugation than clinical strains.
AB  - Mycobacterium avium subsp. hominissuis (MAH) is a widespread opportunistic
      pathogen that can be isolated from environment (dust, soil and water) and
      patients with lung or lymphnode infection. In our previous research we revealed
      the pronounced genetic diversity in MAH by identifying eight different types of a
      newly described genomic island. In order to identify mechanisms of such
      horizontal gene transfer we now analyzed the ability of 47 MAH isolates to
      inherit the conjugative plasmid pRAW from M. marinum. A higher percentage of
      environmental isolates (22.7%) compared to clinical isolates (8%) had the
      capacity to function as recipient in conjugal plasmid transfer. Genetic analysis
      showed additionally that environmental isolates contained more genes homologous
      to genes present on conjugative mycobacterial plasmids than clinical isolates.
      Comparative analysis of the genomes of the isolates pointed to a possible
      association between the ability to act as recipient in conjugation and the
      structure of a genomic region containing the radC gene and a type I
      restriction/modification system. Finally we found that uptake of pRAW decreased
      the resistance against various antibiotics.

PMID- 29343427
TI  - Controlled attenuation parameter and alcoholic hepatic steatosis: Diagnostic
      accuracy and role of alcohol detoxification.
AB  - BACKGROUND & AIMS: Controlled attenuation parameter (CAP) is a novel non-invasive
      measure of hepatic steatosis, but it has not been evaluated in alcoholic liver
      disease. Therefore, we aimed to validate CAP for the assessment of biopsy
      verified alcoholic steatosis and to study the effect of alcohol detoxification on
      CAP. METHODS: This was a cross-sectional biopsy-controlled diagnostic study in
      four European liver centres. Consecutive alcohol-overusing patients underwent
      concomitant CAP, regular ultrasound, and liver biopsy. In addition, we measured
      CAP before and after admission for detoxification in a separate single-centre
      cohort. RESULTS: A total of 562 patients were included in the study: 269 patients
      in the diagnostic cohort with steatosis scores S0, S1, S2, and S3 = 77 (28%), 94
      (35%), 64 (24%), and 34 (13%), respectively. CAP diagnosed any steatosis and
      moderate steatosis with fair accuracy (area under the receiver operating
      characteristic curve [AUC] >=S1 = 0.77; 0.71-0.83 and AUC >=S2 = 0.78; 0.72
      0.83), and severe steatosis with good accuracy (AUC S3 = 0.82; 0.75-0.88). CAP
      was superior to bright liver echo pattern by regular ultrasound. CAP above 290
      dB/m ruled in any steatosis with 88% specificity and 92% positive predictive
      value, while CAP below 220 dB/m ruled out steatosis with 90% sensitivity, but 62%
      negative predictive value. In the 293 patients who were admitted 6.3 days
      (interquartile range 4-6) for detoxification, CAP decreased by 32 +/- 47 dB/m (p
      <0.001). Body mass index predicted higher CAP in both cohorts, irrespective of
      drinking pattern. Obese patients with body mass index >=30 kg/m2 had a
      significantly higher CAP, which did not decrease significantly during
      detoxification. CONCLUSIONS: CAP has a good diagnostic accuracy for diagnosing
      severe alcoholic liver steatosis and can be used to rule in any steatosis. In non
      obese but not in obese, patients, CAP rapidly declines after alcohol withdrawal.
      LAY SUMMARY: CAP is a new ultrasound-based technique for measuring fat content in
      the liver, but has never been tested for fatty liver caused by alcohol. Herein,
      we examined 562 patients in a multicentre setting. We show that CAP highly
      correlates with liver fat, and patients with a CAP value above 290 dB/m were
      highly likely to have more than 5% fat in their livers, determined by liver
      biopsy. CAP was also better than regular ultrasound for determining the severity
      of alcoholic fatty-liver disease. Finally, we show that three in four (non-obese)
      patients rapidly decrease in CAP after short-term alcohol withdrawal. In
      contrast, obese alcohol-overusing patients were more likely to have higher CAP
      values than lean patients, irrespective of drinking.

PMID- 29343428
TI  - Development and pre-clinical evaluation in the swine model of a mucosal vaccine
      tablet for human influenza viruses: A proof-of-concept study.
AB  - Liquid vaccine formulations present some disadvantages such as stability
      problems, cold chain requirement or administration by trained personnel. Vaccine
      formulated as tablets would present a wide range of progress such as an increase
      stability that would facilitate the administration, the distribution and the
      storage of vaccine formulations. This work investigates the possibility to
      develop a mucosal tablet vaccine for human influenza viruses. The tablets were
      tested in vitro for biological efficacy and stability and in vivo in swine as a
      model for influenza A virus immunity. First, the ability to produce by compaction
      a stable vaccine with a preserved antigen was demonstrated. In a second part,
      vaccine tablets were used to immunize pigs. After positioning the tablets on the
      buccal mucosa, the animals were challenged by inoculation of the A/H1N1 pandemic
      virus. The responses were compared to those observed in animals vaccinated
      intramuscularly with the commercial liquid vaccine. It was observed signs of
      priming of the pig's immune system with vaccine tablets, even if the immune
      response stayed lower than vaccination by intramuscular route. Thus, we present
      attractive results that indicate a promising potential for mucosal vaccine
      tablets.

PMID- 29343429
TI  - Translational control of human acetyl-CoA carboxylase 1 mRNA is mediated by an
      internal ribosome entry site in response to ER stress, serum deprivation or
      hypoxia mimetic CoCl2.
AB  - Acetyl-CoA carboxylase 1 (ACC1) is a cytosolic enzyme catalyzing the rate
      limiting step in de novo fatty acid biosynthesis. There is mounting evidence
      showing that ACC1 is susceptible to dysregulation and that it is over-expressed
      in liver diseases associated with lipid accumulation and in several cancers. In
      the present study, ACC1 regulation at the translational level is reported. Using
      several experimental approaches, the presence of an internal ribosome entry site
      (IRES) has been established in the 5' untranslated region (5' UTR) of the ACC1
      mRNA. Transfection experiments with the ACC1 5' UTR inserted in a dicistronic
      reporter vector show a remarkable increase in the downstream cistron translation,
      through a cap-independent mechanism. The endoplasmic reticulum (ER) stress
      condition and the related unfolded protein response (UPR), triggered by treatment
      with thapsigargin and tunicamycin, cause an increase of the cap-independent
      translation of ACC1 mRNA in HepG2 cells, despite the overall reduction in global
      protein synthesis. Other stress conditions, such as serum starvation and
      incubation with hypoxia mimetic agent CoCl2, up-regulate ACC1 expression in HepG2
      cells at the translational level. Overall, these findings indicate that the
      presence of an IRES in the ACC1 5' UTR allows ACC1 mRNA translation in conditions
      that are inhibitory to cap-dependent translation. A potential involvement of the
      cap-independent translation of ACC1 in several pathologies, such as obesity and
      cancer, has been discussed.

PMID- 29343430
TI  - Cardiolipin synthesizing enzymes form a complex that interacts with cardiolipin
      dependent membrane organizing proteins.
AB  - The mitochondrial glycerophospholipid cardiolipin plays important roles in
      mitochondrial biology. Most notably, cardiolipin directly binds to mitochondrial
      proteins and helps assemble and stabilize mitochondrial multi-protein complexes.
      Despite their importance for mitochondrial health, how the proteins involved in
      cardiolipin biosynthesis are organized and embedded in mitochondrial membranes
      has not been investigated in detail. Here we show that human PGS1 and CLS1 are
      constituents of large protein complexes. We show that PGS1 forms oligomers and
      associates with CLS1 and PTPMT1. Using super-resolution microscopy, we observed
      well-organized nanoscale structures formed by PGS1. Together with the observation
      that cardiolipin and CLS1 are not required for PGS1 to assemble in the complex we
      predict the presence of a PGS1-centered cardiolipin-synthesizing scaffold within
      the mitochondrial inner membrane. Using an unbiased proteomic approach we found
      that PGS1 and CLS1 interact with multiple cardiolipin-binding mitochondrial
      membrane proteins, including prohibitins, stomatin-like protein 2 and the MICOS
      components MIC60 and MIC19. We further mapped the protein-protein interaction
      sites between PGS1 and itself, CLS1, MIC60 and PHB. Overall, this study provides
      evidence for the presence of a cardiolipin synthesis structure that transiently
      interacts with cardiolipin-dependent protein complexes.

PMID- 29343431
TI  - Gasdermin D Flashes an Exit Signal for IL-1.
AB  - The IL-1 family of cytokines follows an unconventional pathway of secretion
      mostly associated with inflammatory cell death. In this issue of Immunity,
      (Evavold et al., 2017) report gasdermin D pores as channels for active IL-1
      release in live phagocytic cells.

PMID- 29343432
TI  - HIV Immunogens: Affinity Is Key.
AB  - Generation of broadly neutralizing antibodies is a key aim of HIV vaccine design,
      but the precursor B cells are rare. Abbott et al. (2018) report that high
      affinity and avidity immunogens are required to promote maturation of low
      frequency B cells in germinal centers.

PMID- 29343434
TI  - A Long-Distance Relay-tionship between Tumor and Bone.
AB  - Myeloid cells, including neutrophils, are important regulators of tumor growth
      and metastasis. In Science, Engblom et al. (2017) reveal how lung tumors remotely
      engage bone-resident cells through a relay mechanism that achieves a sustained
      supply of tumor-promoting neutrophils.

PMID- 29343433
TI  - Oxysterol Sensing through the Receptor GPR183 Promotes the Lymphoid-Tissue
      Inducing Function of Innate Lymphoid Cells and Colonic Inflammation.
AB  - Group 3 innate lymphoid cells (ILC3s) sense environmental signals and are
      critical for tissue integrity in the intestine. Yet, which signals are sensed and
      what receptors control ILC3 function remain poorly understood. Here, we show that
      ILC3s with a lymphoid-tissue-inducer (LTi) phenotype expressed G-protein-coupled
      receptor 183 (GPR183) and migrated to its oxysterol ligand 7alpha,25
      hydroxycholesterol (7alpha,25-OHC). In mice lacking Gpr183 or 7alpha,25-OHC,
      ILC3s failed to localize to cryptopatches (CPs) and isolated lymphoid follicles
      (ILFs). Gpr183 deficiency in ILC3s caused a defect in CP and ILF formation in the
      colon, but not in the small intestine. Localized oxysterol production by
      fibroblastic stromal cells provided an essential signal for colonic lymphoid
      tissue development, and inflammation-induced increased oxysterol production
      caused colitis through GPR183-mediated cell recruitment. Our findings show that
      GPR183 promotes lymphoid organ development and indicate that oxysterol-GPR183
      dependent positioning within tissues controls ILC3 activity and intestinal
      homeostasis.

PMID- 29343436
TI  - Motile Collectors: Platelets Promote Innate Immunity.
AB  - Platelets migrate in vitro but the significance of platelet migration in vivo
      remains unclear. In a recent issue of Cell, Gaertner et al. (2017) demonstrate
      that active platelet migration in vivo promotes mechano-scavenging of bacterial
      pathogens and neutrophil activation.

PMID- 29343435
TI  - Paracrine Wnt5a-beta-Catenin Signaling Triggers a Metabolic Program that Drives
      Dendritic Cell Tolerization.
AB  - Despite recent advances, many cancers remain refractory to available
      immunotherapeutic strategies. Emerging evidence indicates that the tolerization
      of local dendritic cells (DCs) within the tumor microenvironment promotes immune
      evasion. Here, we have described a mechanism by which melanomas establish a site
      of immune privilege via a paracrine Wnt5a-beta-catenin-peroxisome proliferator
      activated receptor-gamma (PPAR-gamma) signaling pathway that drives fatty acid
      oxidation (FAO) in DCs by upregulating the expression of the carnitine
      palmitoyltransferase-1A (CPT1A) fatty acid transporter. This FAO shift increased
      the protoporphyrin IX prosthetic group of indoleamine 2,3-dioxgenase-1 (IDO)
      while suppressing interleukin(IL)-6 and IL-12 cytokine expression, culminating in
      enhanced IDO activity and the generation of regulatory T cells. We demonstrated
      that blockade of this pathway augmented anti-melanoma immunity, enhanced the
      activity of anti-PD-1 antibody immunotherapy, and suppressed disease progression
      in a transgenic melanoma model. This work implicates a role for tumor-mediated
      metabolic reprogramming of local DCs in immune evasion and immunotherapy
      resistance.

PMID- 29343437
TI  - Memory B Cells that Cross-React with Group 1 and Group 2 Influenza A Viruses Are
      Abundant in Adult Human Repertoires.
AB  - Human B cell antigen-receptor (BCR) repertoires reflect repeated exposures to
      evolving influenza viruses; new exposures update the previously generated B cell
      memory (Bmem) population. Despite structural similarity of hemagglutinins (HAs)
      from the two groups of influenza A viruses, cross-reacting antibodies (Abs) are
      uncommon. We analyzed Bmem compartments in three unrelated, adult donors and
      found frequent cross-group BCRs, both HA-head directed and non-head directed.
      Members of a clonal lineage from one donor had a BCR structure similar to that of
      a previously described Ab, encoded by different gene segments. Comparison showed
      that both Abs contacted the HA receptor-binding site through long heavy-chain
      third complementarity determining regions. Affinities of the clonal-lineage BCRs
      for historical influenza-virus HAs from both group 1 and group 2 viruses
      suggested that serial responses to seasonal influenza exposures had elicited the
      lineage and driven affinity maturation. We propose that appropriate immunization
      regimens might elicit a comparably broad response.

PMID- 29343439
TI  - The Family of LPS Signal Transducers Increases: the Arrival of Chanzymes.
AB  - After LPS recognition, the MyD88-dependent and the TRIF-dependent pathways are
      consecutively activated in macrophages. Schappe et al. (2018) show that the
      chanzyme TRPM7 is required for an efficient LPS receptor complex endosomal
      relocation and the activation of the TRIF pathway.

PMID- 29343441
TI  - moDCs, Less Problems.
AB  - Type 1 conventional dendritic cells are necessary for the development of anti
      tumor immunity. In this issue of Immunity, Sharma et al. (2018) identify a
      phenotypically similar monocyte-derived population within inflamed tumors that
      promotes T cell responses during therapy.

PMID- 29343438
TI  - Regulation of the Immune Response by the Aryl Hydrocarbon Receptor.
AB  - The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor
      that is activated by small molecules provided by the diet, microorganisms,
      metabolism, and pollutants. AhR is expressed by a number of immune cells, and
      thus AhR signaling provides a molecular pathway that integrates the effects of
      the environment and metabolism on the immune response. Studies have shown that
      AhR signaling plays important roles in the immune system in health and disease.
      As its activity is regulated by small molecules, AhR also constitutes a potential
      target for therapeutic immunomodulation. In this review we discuss the role of
      AhR in the regulation of the immune response in the context of autoimmunity,
      infection, and cancer, as well as the potential opportunities and challenges of
      developing AhR-targeted therapeutics.

PMID- 29343440
TI  - Chanzyme TRPM7 Mediates the Ca2+ Influx Essential for Lipopolysaccharide-Induced
      Toll-Like Receptor 4 Endocytosis and Macrophage Activation.
AB  - Toll-like receptors (TLRs) sense pathogen-associated molecular patterns to
      activate the production of inflammatory mediators. TLR4 recognizes
      lipopolysaccharide (LPS) and drives the secretion of inflammatory cytokines,
      often contributing to sepsis. We report that transient receptor potential
      melastatin-like 7 (TRPM7), a non-selective but Ca2+-conducting ion channel,
      mediates the cytosolic Ca2+ elevations essential for LPS-induced macrophage
      activation. LPS triggered TRPM7-dependent Ca2+ elevations essential for TLR4
      endocytosis and the subsequent activation of the transcription factor IRF3. In a
      parallel pathway, the Ca2+ signaling initiated by TRPM7 was also essential for
      the nuclear translocation of NFkappaB. Consequently, TRPM7-deficient macrophages
      exhibited major deficits in the LPS-induced transcriptional programs in that they
      failed to produce IL-1beta and other key pro-inflammatory cytokines. In accord
      with these defects, mice with myeloid-specific deletion of Trpm7 are protected
      from LPS-induced peritonitis. Our study highlights the importance of Ca2+
      signaling in macrophage activation and identifies the ion channel TRPM7 as a
      central component of TLR4 signaling.

PMID- 29343443
TI  - New Job for NK Cells: Architects of the Tumor Microenvironment.
AB  - NK cells control tumor growth directly through targeted cytotoxic granule release
      or cytokine secretion and indirectly by orchestrating anti-tumor immune
      responses. In this issue of Immunity, Glasner et al. (2018) now reveal a new role
      for NK cells in preventing metastatic spread through controlling tumor
      architecture.

PMID- 29343442
TI  - The Transcription Factor STAT6 Mediates Direct Repression of Inflammatory
      Enhancers and Limits Activation of Alternatively Polarized Macrophages.
AB  - The molecular basis of signal-dependent transcriptional activation has been
      extensively studied in macrophage polarization, but our understanding remains
      limited regarding the molecular determinants of repression. Here we show that IL
      4-activated STAT6 transcription factor is required for the direct transcriptional
      repression of a large number of genes during in vitro and in vivo alternative
      macrophage polarization. Repression results in decreased lineage-determining
      transcription factor, p300, and RNA polymerase II binding followed by reduced
      enhancer RNA expression, H3K27 acetylation, and chromatin accessibility. The
      repressor function of STAT6 is HDAC3 dependent on a subset of IL-4-repressed
      genes. In addition, STAT6-repressed enhancers show extensive overlap with the NF
      kappaB p65 cistrome and exhibit decreased responsiveness to lipopolysaccharide
      after IL-4 stimulus on a subset of genes. As a consequence, macrophages exhibit
      diminished inflammasome activation, decreased IL-1beta production, and
      pyroptosis. Thus, the IL-4-STAT6 signaling pathway establishes an alternative
      polarization-specific epigenenomic signature resulting in dampened macrophage
      responsiveness to inflammatory stimuli.

PMID- 29343446
TI  - S-adenosyl methionine prevents ASD like behaviors triggered by early postnatal
      valproic acid exposure in very young mice.
AB  - INTRODUCTION: A common animal model of ASD is the one induced by valproic acid
      (VPA), inducing epigenetic changes and oxidative stress. We studied the possible
      preventive effect of the methyl donor for epigenetic enzymatic reactions, S
      adenosine methionine (SAM), on ASD like behavioral changes and on redox potential
      in the brain and liver in this model. METHODS: ICR albino mice were injected on
      postnatal day 4 with one dose of 300 mg/kg of VPA, with normal saline (controls)
      or with VPA and SAM that was given orally for 3 days at the dose of 30 mg/kg body
      weight. From day 50, we carried out neurobehavioral tests and assessment of the
      antioxidant status of the prefrontal cerebral cortex, liver assessing SOD and CAT
      activity, lipid peroxidation and the expression of antioxidant genes. RESULTS:
      Mice injected with VPA exhibited neurobehavioral deficits typical of ASD that
      were more prominent in males. Changes in the activity of SOD and CAT increased
      lipid peroxidation and changes in the expression of antioxidant genes were
      observed in the prefrontal cortex of VPA treated mice, more prominent in females,
      while ASD like behavior was more prominent in males. There were no changes in the
      redox potential of the liver. The co-administration of VPA and SAM alleviated
      most ASD like neurobehavioral symptoms and normalized the redox potential in the
      prefrontal cortex. CONCLUSIONS: Early postnatal VPA administration induces ASD
      like behavior that is more severe in males, while the redox status changes are
      more severe in females; SAM corrects both. VPA-induced ASD seems to result from
      epigenetic changes, while the redox status changes may be secondary.

PMID- 29343444
TI  - Activation of p53 in Immature Myeloid Precursor Cells Controls Differentiation
      into Ly6c+CD103+ Monocytic Antigen-Presenting Cells in Tumors.
AB  - CD103+ dendritic cells are critical for cross-presentation of tumor antigens.
      Here we have shown that during immunotherapy, large numbers of cells expressing
      CD103 arose in murine tumors via direct differentiation of Ly6c+ monocytic
      precursors. These Ly6c+CD103+ cells could derive from bone-marrow monocytic
      progenitors (cMoPs) or from peripheral cells present within the myeloid-derived
      suppressor cell (MDSC) population. Differentiation was controlled by inflammation
      induced activation of the transcription factor p53, which drove upregulation of
      Batf3 and acquisition of the Ly6c+CD103+ phenotype. Mice with a targeted deletion
      of p53 in myeloid cells selectively lost the Ly6c+CD103+ population and became
      unable to respond to multiple forms of immunotherapy and immunogenic
      chemotherapy. Conversely, increasing p53 expression using a p53-agonist drug
      caused a sustained increase in Ly6c+CD103+ cells in tumors during immunotherapy,
      which markedly enhanced the efficacy and duration of response. Thus, p53-driven
      differentiation of Ly6c+CD103+ monocytic cells represents a potent and previously
      unrecognized target for immunotherapy.

PMID- 29343445
TI  - Development, regulation, metabolism and function of bone marrow adipose tissues.
AB  - Most adipocytes exist in discrete depots throughout the body, notably in well
      defined white and brown adipose tissues. However, adipocytes also reside within
      specialized niches, of which the most abundant is within bone marrow. Whereas
      bone marrow adipose tissue (BMAT) shares many properties in common with white
      adipose tissue, the distinct functions of BMAT are reflected by its development,
      regulation, protein secretion, and lipid composition. In addition to its
      potential role as a local energy reservoir, BMAT also secretes proteins,
      including adiponectin, RANK ligand, dipeptidyl peptidase-4, and stem cell factor,
      which contribute to local marrow niche functions and which may also influence
      global metabolism. The characteristics of BMAT are also distinct depending on
      whether marrow adipocytes are contained within yellow or red marrow, as these can
      be thought of as 'constitutive' and 'regulated', respectively. The rBMAT for
      instance can be expanded or depleted by myriad factors, including age, nutrition,
      endocrine status and pharmaceuticals. Herein we review the site specificity, age
      related development, regulation and metabolic characteristics of BMAT under
      various metabolic conditions, including the functional interactions with bone and
      hematopoietic cells.

PMID- 29343447
TI  - Altered B lymphocyte homeostasis and functions in systemic sclerosis.
AB  - Beyond the production of autoantibodies, B-cells are thought to play a role in
      systemic sclerosis (SSc) by secreting proinflammatory/profibrotic cytokines. B
      cells are a heterogeneous population with different subsets distinguished by
      their phenotypes and cytokine production. Data about B-cell subsets, cytokine
      production and intracellular pathways leading to this production are scarce in
      SSc. The aim of our study was to describe B-cell homeostasis, activation,
      proliferation, cytokine production in B-cells and serum and B-cell intracellular
      signaling pathways in SSc. We hypothezided that B-cell homeostasis and cytokine
      production were altered in SSc and could be explained by serum cytokine as well
      as by intracellular signaling pathway abnormalities. Forty SSc patients and 20
      healthy controls (HC) were prospectively included. B-cell subsets were determined
      by flow cytometry using CD19, CD21, CD24, CD38, CD27, IgM and IgD. CD25, CD80,
      CD95, HLA-DR were used to assess B-cell activation. Intracellular production of
      IL-10 and IL-6 were assessed by flow cytometry after TLR9 and CD40 stimulation.
      IL-6, IL-10, Ki67, Bcl2 mRNA were quantified in B-cells. Cytokine production was
      also assessed in sera and supernatants of B-cell culture, using a multiplex
      approach. Signaling pathways were studied through phosphorylation of mTOR, ERK,
      STAT3, STAT5 using a flow cytometry approach. We found that SSc patients
      exhibited an altered peripheral blood B-cell subset distribution, with decreased
      memory B-cells but increased proportion of naive and CD21LoCD38Lo B-cell subsets.
      We observed an increased expression of activation markers (CD80, CD95, HLA-DR) on
      some B-cell subsets, mainly the memory B-cells. Secretion of IL-6, BAFF and
      CXCL13 were increased in SSc sera. There was no correlation between the
      peripheral blood B-cell subsets and the serum concentrations of these cytokines.
      After stimulation, we observed a lower proportion of IL-10 and IL-6 producing B
      cells in SSc. Finally, we observed a significant decrease of mTOR phosphorylation
      in SSc patient B-cells. In conclusion, we observed an altered B-cell homeostasis
      in SSc patients compared to HC. Memory B-cells were both decreased and activated
      in patients. IL-10 producing B-cells were decreased in SSc. This decrease was
      associated with an alteration of mTOR phosphorylation in B-cells. Conversely,
      there was no correlation between serum cytokine profile and B-cell homeostasis
      alterations.

PMID- 29343449
TI  - The comparative efficacy and safety of topical and intravenous tranexamic acid
      for reducing perioperative blood loss in Total knee arthroplasty- A randomized
      controlled non-inferiority trial.
AB  - BACKGROUND: Total Knee Arthroplasty (TKA) can be associated with significant
      perioperative blood loss and blood transfusions. This is a prospective randomised
      non-inferiority trial comparing intraarticular (IA) and intravenous (IV) routes
      of administering Tranexamic acid (TXA) with regard to efficacy and safety.
      METHODS: A total of 113 patients who underwent primary unilateral TKA from
      January to June 2017 randomly received either 1.5g TXA in 100mL normal saline
      solution (IA group, n=58) or 10mg/kg TXA (IV group, n=55) at 10min before the
      tourniquet inflation and at tourniquet release. Haemoglobin (Hb) drop on third
      day (primary outcome), visible blood loss (VBL), hidden blood loss (HBL), total
      blood loss (TBL), transfusion requirement, incidence of deep vein thrombosis
      (DVT), wound complications and renal function derangement (secondary outcomes)
      were recorded. RESULTS: The mean difference in haemoglobin drop between both
      groups was 0.25g/dL with 90% CI of -0.07 to 0.58. Since the lower bound of 90% CI
      was above equivalence margin of -0.35, IA group was found to be non-inferior to
      IV group in terms of Hb drop. The mean difference between both groups of VBL, HBL
      and TBL were 0.85mL (p value 0.90), -7.9mL (p value 0.90) and -6.2mL (p value
      0.93) respectively. Transfusions and wound complications were statistically
      insignificant. None of the patients had DVT or renal function derangement.
      CONCLUSION: IA TXA is not inferior to IV TXA with regard to efficacy and safety
      and may be preferred considering ease of administration and lack of systemic
      absorption.

PMID- 29343448
TI  - Optimizing the dose of local infiltration analgesia and gabapentin for total knee
      arthroplasty, a randomized single blind trial in 128 patients.
AB  - BACKGROUND AND PURPOSE: Effective analgesia is essential for postoperative
      recovery and rehabilitation in TKA. The challenge of analgesic regimes is to
      obtain adequate pain relief and maximum muscle control to mobilize and
      rehabilitate patients early. However, the optimal dose and best composition are
      not known. We hypothesized that there would be no differences in reported
      postoperative pain on the day of the TKA surgery as well as the first day after
      surgery when different combinations of ropivacain for LIA and gabapentin are
      given. METHODS: This prospective randomized trial examined 128 TKA patients
      treated with LIA and gabapentin in four groups. Group A: 300-mg ropivacain/600
      300-300-mg gabapentin. Group B: 150-mg ropivacain/600-300-300-mg gabapentin.
      Group C: 300-mg ropivacain/300-100-100-mg gabapentin. Group D: 150-mg
      ropivacain/300-100-100-mg gabapentin. Primary endpoint was pain (NRS) at multiple
      moments. Secondary endpoints were number of adverse effects, length of hospital
      stay (LOS), the amount of consumption of pain medication, and wound leakage.
      Generalized estimating equation (GEE) was used to detect differences between the
      four groups regarding the course of pain. RESULTS: No differences regarding
      adverse effects, LOS, and wound leakage were found. GEE revealed a significant
      difference in course of pain between group A and B, with group B experiencing
      higher NRS scores postoperatively than group A (p=0.021). No differences between
      the other groups were found. INTERPRETATION: The results of the current study
      suggest that LIA with 300-mg (150ml) ropivacain might be more effective than 150
      mg (75ml) ropivacain. Alteration in dose of gabapentin appears not to have
      influence on the course of pain.

PMID- 29343450
TI  - Paediatric physeal sparing posterior cruciate ligament (PCL) reconstruction with
      parental donation allograft: Rationale and operative approach.
AB  - BACKGROUND: Paediatric PCL injuries are rare but constitute a significant
      management challenge. We describe a novel approach to the surgical management of
      an 11-year-old boy who presented with persisting symptomatic instability
      following 18months of failed conservative therapy. METHODS: PCL reconstruction
      was performed using a physeal sparing, all-inside technique under fluoroscopic
      control. This avoids the potential for iatrogenic growth injury. A parentally
      donated hamstrings allograft was used to ensure adequate graft size, and
      reinforced using a non-elastic two millimetre braided suture. Graft reinforcement
      safeguards against stretching during the early healing phase, but must be removed
      thereafter to avoid creating a physeal tether. RESULTS: At three months, clinical
      examination under anaesthesia showed equivalent PCL laxity in the operated knee
      compared to the normal contralateral knee. The graft reinforcement tape was
      incised as planned with no change in laxity assessment. Arthroscopic evaluation
      demonstrated a quiet joint with a well healed graft and no synovitis.
      Postoperative long leg radiographs showed no growth deformity against
      preoperative status. CONCLUSION: In paediatric patients with persisting
      symptomatic instability despite appropriate conservative management, surgical
      reconstruction of the PCL should be considered. Standard treatment has higher
      complication rates and poorer graft survival than in an adult cohort. Specific
      problems include iatrogenic growth plate injury causing growth arrest or angular
      deformity, inadequate graft size if using hamstrings autograft, and the
      additional technical challenge of small patient size. Early results from extra
      physeal, all-inside PCL reconstruction using a parentally donated allograft are
      promising and may provide an alternative solution to traditional surgical
      management.

PMID- 29343451
TI  - Biochemical characterization of halophilic, alkalithermophilic amylopullulanase
      PulD7 and truncated amylopullulanases PulD7DeltaN and PulD7DeltaC.
AB  - A pullulanase, PulD7, was identified in the genome of the halophilic,
      alkalithermophilic isolate Alkalilimnicola sp. NM-DCM-1. PulD7 is 701 amino acids
      large with a carbohydrate binding module (CBM) 48 at the N-terminal. The full
      length PulD7 and N- and C-terminal truncated versions were cloned, heterologously
      expressed and functionally characterized. PulD7 displayed maximal activity at 55 
      degrees C, pH 9.5 and 2 M NaCl. PulD7 had good thermal stability, with a half
      life of 693 min at 50  degrees C. PulD7 is an amylopullulanase, hydrolyzing both
      alpha-1,4- and alpha-1,6-glycosidic bonds in soluble starch and pullulan,
      respectively. PulD7 was resistant to chemical reagents, including organic
      solvents (dimethyl sulfoxide, methanol, benzene, 20% v/v), reducing agents (beta
      mercaptoethanol, 5% v/v), surfactants (SDS and Tween 20, 5% v/v), the divalent
      chelator ethylene diamine tetra acetic acid (5 mM), and the chemical denaturant
      urea (8 M). PulD7 was not calcium-dependent. PulD7 was able to bind raw starch
      granules, reaching 52% binding in 3 h. The N-and C-terminal truncated forms of
      PulD7 had similar biochemical characteristics. PulD7DeltaC had higher specific
      activity and halotolerance. The N-terminally truncated PulD7DeltaN hydrolyzed
      amylose only, indicating that CBM48 is essential for binding branched substrates.
      PulD7 has unique characteristics giving it strong potential for application in
      biotechnological industries.

PMID- 29343452
TI  - A cell-penetrating peptide conjugated carboxymethyl-beta-cyclodextrin to improve
      intestinal absorption of insulin.
AB  - In this study, a cell-penetrating peptide conjugate, R8-carboxymethyl-beta
      cyclodextrin (R8-CM-beta-CD), was synthesized, and then we prepared the
      supramolecular complex (insulin/R8-CM-beta-CD). The physicochemical properties of
      the complex were characterized. The supramolecular complex could facilitate the
      uptake of insulin, meanwhile, induce a significantly higher internalization of
      insulin. Interestingly, the transportation efficiency of insulin/R8-CM-beta-CD
      across the Caco-2 cell monolayer was about 3 times greater than that of
      insulin/CM-beta-CD. Further studies on the mechanism in increasing uptake
      efficiency showed that R8-CM-beta-CD was internalized via different styles of
      endocytosis and could inhibit P-glycoprotein (P-gp) efflux pumps. Importantly,
      the formulation of insulin/R8-CM-beta-CD showed the highest increase in the
      permeability of insulin and the best biological response in diabetic rats of all
      the treatments. In addition, no sign of toxicity was observed after
      administrations of R8-CM-beta-CD. These results demonstrated that R8-CM-beta-CD
      was a promising carrier for use in protein drug delivery.

PMID- 29343453
TI  - Polygonatum sibiricum polysaccharides play anti-cancer effect through TLR4
      MAPK/NF-kappaB signaling pathways.
AB  - OBJECTIVE: To investigate the anti-cancer effect of Polygonatum sibiricum
      polysaccharides (PSP) and the underlying mechanism. METHODS: Tumor-bearing mice
      were randomly divided into normal saline (NS) group, adriamycin (ADM) group, PSP
      group and lipopolysaccharide (LPS) group. RAW264.7 cells were pre-treated with or
      without TLR4 inhibitor or MyD88 inhibitor. Quantitative RT-PCR and Western blot
      were performed to detect the mRNA and protein expressions, respectively. ELISA
      and Griess reaction was used to measure cytokines and NO levels. Flow cytometry
      was employed to examine T-lymphocyte subset and CCK-8 assay was used for cell
      viability. RESULTS: The in vivo experiment found that PSP inhibited tumor growth
      and improved the spleen index, thymus index, the cytokines secretion and
      CD4+/CD8+ lymphocytes ratio. Compared with the NS group, the mRNA and protein
      expressions of the critical nodes inTLR4-MAPK/NF-kappaB signaling pathways
      (except TRAM) significantly increased in PSP group, as well as the NO and
      cytokines levels. Nevertheless, PSP had no obvious effects on TRAM. Further
      analysis showed that PSP effects on the critical nodes in TLR4-MAPK/NF-kappaB
      signaling pathways were suppressed by inhibitor in vitro. CONCLUSION: The
      immunoenhancement effect of PSP against lung cancer is mediated by TLR4-MAPK/NF
      kappaB signaling pathways.

PMID- 29343454
TI  - Rational design and evaluation of HBsAg polymeric nanoparticles as antigen
      delivery carriers.
AB  - The present work is focused on the development and evaluation of single dose
      sustained-release Hepatitis B surface antigen (HBsAg) loaded nanovaccine for
      Hepatitis B. The conventional treatment suffers from repeated administration and
      hence requires a booster dose. Therefore, polymeric nanovaccine of HBsAg was
      developed by double emulsion solvent evaporation technique, utilizing central
      composite design for formulation optimization. The effects of independent
      variables (like polymer amount, stabilizer concentration, aqueous/organic phase
      ratio and homogenizer speed) were also studied on critical quality attributes
      like particle size and entrapment efficiency. Nanovaccine was characterized in
      terms of physicochemical parameters, release, internalization and in vivo
      immunological evaluation in BALB/c mice after administration by different routes
      such as oral, sub-cutaneous, nasal and intramuscular. The designed nanovaccine
      demonstrated nanometric size with smooth surface, negative zeta potential,
      maximum entrapment, sustained release and better internalization in macrophage
      and MRC-5 cell line. The immune-stimulating activity of nanovaccine administered
      by different routes was evaluated by measuring anti-HBsAg titre like specific
      immunoglobulin IgG and IgA response and cytokine level (interleukin-2, interferon
      Y) measurement. The results indicated that the nanovaccine administered by
      intramuscular route produced better humoral as well as cellular responses and
      potential carriers for antigen delivery at single dose administration via
      intramuscular route.

PMID- 29343456
TI  - EEG Dynamics and Neural Generators in Implicit Navigational Image Processing in
      Adults with ADHD.
AB  - In contrast to childhood ADHD that is characterized by inattention, impulsivity
      and hyperactivity, most adults with ADHD predominantly exhibit inattention. We
      used a new oddball paradigm using implicit navigational images and analyzed EEG
      dynamics with swLORETA inverse modeling of the evoked potential generators to
      study cortical processing in adults with ADHD and age-matched controls. In
      passive observation, we demonstrated that P350 amplitude, alpha-beta oscillation
      event-related synchronization (ERS) anticipation, and beta event-related
      desynchronization (ERD) were significantly smaller in ADHD. In the active
      condition, P100 duration was reduced and N140 amplitude increased for both
      deviant and frequent conditions in the ADHD. Alpha ERS and delta-theta ERS were
      reduced in the ADHD in the deviant condition. The left somatosensory area (BA2)
      and the right parietal lobe (BA31, BA40) contributed more to the P100 generators
      in the control than in the ADHD group, while the left frontal lobe (BA10)
      contributed more to the P100 generators in the ADHD. The left inferior parietal
      lobe (BA40) contributed more to the N140 generators in the control than the ADHD
      group while the right posterior cingulate (BA30) contributed more to the N140
      generators in the ADHD. These findings reinforce the notion that earlier cortical
      stages of visual processing are compromised in adult ADHD by inducing the
      emergence of different even-related potential generators and EEG dynamics in
      ADHD. Considering that classical approaches for ADHD diagnosis are based on
      qualitative clinical investigation possibly biased by subjectivity, EEG analysis
      is another objective tool that might contribute to diagnosis, future
      neurofeedback or brain stimulation therapies.

PMID- 29343457
TI  - Sphingolipid signaling in renal fibrosis.
AB  - Over the last decade, various sphingolipid subspecies have gained increasing
      attention as important signaling molecules that regulate a multitude of
      physiological and pathophysiological processes including inflammation and tissue
      remodeling. These mediators include ceramide, sphingosine 1-phosphate (S1P), the
      cerebroside glucosylceramide, lactosylceramide, and the gangliosides GM3 and Gb3.
      These lipids have been shown to accumulate in various chronic kidney diseases
      that typically end in renal fibrosis and ultimately renal failure. This review
      will summarize the effects and contributions of those enzymes that regulate the
      generation and interconversion of these lipids, notably the acid
      sphingomyelinase, the acid sphingomyelinase-like protein SMPDL3B, the sphingosine
      kinases, the S1P lyase, the glucosylceramide synthase, the GM3 synthase, and the
      alpha-galactosidase A, to renal fibrotic diseases. Strategies of manipulating
      these enzymes for therapeutic purposes and the impact of existing drugs on renal
      pathologies will be discussed.

PMID- 29343455
TI  - Adolescent Social Stress Increases Anxiety-like Behavior and Alters Synaptic
      Transmission, Without Influencing Nicotine Responses, in a Sex-Dependent Manner.
AB  - Early-life stress is a risk factor for comorbid anxiety and nicotine use. Because
      little is known about the factors underlying this comorbidity, we investigated
      the effects of adolescent stress on anxiety-like behavior and nicotine responses
      within individual animals. Adolescent male and female C57BL/6J mice were exposed
      to chronic variable social stress (CVSS; repeated cycles of social isolation +
      social reorganization) or control conditions from postnatal days (PND) 25-59.
      Anxiety-like behavior and social avoidance were measured in the elevated plus
      maze (PND 61-65) and social approach-avoidance test (Experiment 1: PND 140-144;
      Experiment 2: 95-97), respectively. Acute nicotine-induced locomotor,
      hypothermic, corticosterone responses, (Experiment 1: PND 56-59; Experiment 2:
      PND 65-70) and voluntary oral nicotine consumption (Experiment 1: PND 116-135;
      Experiment 2: 73-92) were also examined. Finally, we assessed prefrontal cortex
      (PFC) and nucleus accumbens (NAC) synaptic transmission (PND 64-80); brain
      regions that are implicated in anxiety and addiction. Mice exposed to adolescent
      CVSS displayed increased anxiety-like behavior relative to controls. Further,
      CVSS altered synaptic excitability in PFC and NAC neurons in a sex-specific
      manner. For males, CVSS decreased the amplitude and frequency of spontaneous
      excitatory postsynaptic currents in the PFC and NAC, respectively. In females,
      CVSS decreased the amplitude of spontaneous inhibitory postsynaptic currents in
      the NAC. Adolescent CVSS did not affect social avoidance or nicotine responses
      and anxiety-like behavior was not reliably associated with nicotine responses
      within individual animals. Taken together, complex interactions between PFC and
      NAC function may contribute to adolescent stress-induced anxiety-like behavior
      without influencing nicotine responses.

PMID- 29343458
TI  - Right ventricular fibrosis and dysfunction: Actual concepts and common
      misconceptions.
AB  - Fibrosis and remodeling of the right ventricle (RV) are associated with RV
      dysfunction and mortality of patients with pulmonary hypertension (PH) but it is
      unknown how much RV fibrosis contributes to RV dysfunction and mortality. RV
      fibrosis manifests as fibroblast accumulation and collagen deposition which may
      be excessive. Although extracellular matrix deposition leads to elevated
      ventricular stiffness, it is not known to which extent it affects RV function.
      Various animal models of pulmonary hypertension have been established to
      investigate the role of fibrosis in RV dysfunction and failure. However, they do
      not perfectly resemble the human disease. In the current review we describe the
      major characteristics of RV fibrosis, molecular mechanisms regulating the
      fibrotic process, and discuss how therapeutic targeting of fibrosis might affect
      RV function.

PMID- 29343459
TI  - Differing structural properties of foods affect the development of mandibular
      control and muscle coordination in infants and young children.
AB  - The development of chewing is an essential motor skill that is continually
      refined throughout early childhood. From a motor control perspective, the
      advancement of textures is dependent upon the fit between a child's oral anatomic
      and motor system and food properties. The purpose of this exploratory study is to
      identify age-related changes in chewing motor coordination and control and to
      determine if these changes are associated with the differing structural
      properties of solid foods, as well as to explore the role of explanatory
      variables such as the emergence of teeth and bite force. The masticatory muscle
      coordination (i.e., coupling of synergistic and antagonistic muscle pairs) and
      control (i.e., speed, displacement, chewing rate, duration, and number of chews)
      of fifty children were assessed cross-sectionally at five ages: 9-, 12-, 18-, 24
      , and 36-months using electromyography (EMG) and 3D optical motion capture while
      children ate three foods that had differing structural properties. The results of
      this study found that children made gains in their chewing motor control
      (decreased duration of chewing sequences and lateral jaw displacement) and
      coordination (improved jaw muscle coupling) throughout this period. The
      structural differences in foods also affected chewing performance at all ages.
      These preliminary findings suggest that some solid textures are better adapted
      for immature mandibular control than others and that the development of chewing
      is a protracted process that may be impacted by the emergence of teeth and
      changes to bite force.

PMID- 29343460
TI  - Facebook Groups for the Management of Chronic Diseases.
AB  - The use of Facebook groups by health care researchers and professionals for
      chronic disease management, namely type 2 diabetes mellitus and coronary heart
      disease, is in its early stages and challenges are emerging. While Facebook
      groups offer great potential to deliver health support, research of Facebook
      groups for chronic disease management remains in its infancy, with robust
      evidence not yet available. Designing Facebook groups that are acceptable to
      users, health care researchers as well as health care professionals is a
      challenge, and there is a poor fit with traditional research and evaluation
      methods. Key recommendations for future research of Facebook groups for chronic
      disease management include: (1) iterative content development with input from the
      target patient population; (2) further understanding of the potential role of
      group "champions"; (3) ensuring the social media policies of health care
      institutions allow for real time online communication; and (4) utilizing
      comprehensive evaluation strategies, including the use of process evaluations.

PMID- 29343462
TI  - A Tailored Web-based Advice Tool for Skiers and Snowboarders: Protocol for a
      Randomized Controlled Trial.
AB  - BACKGROUND: Being active in sports has many positive health effects. The direct
      effects of engaging in regular physical activity are particularly apparent in the
      prevention of several chronic diseases, including cardiovascular disease,
      diabetes, cancer, hypertension, obesity, depression, and osteoporosis. Besides
      the beneficial health effects of being active, sports participation is
      unfortunately also associated with a risk of injuries. In the case of many sports
      injuries (eg, winter sports) preventive measures are not compulsory, which means
      that a behavioral change in sports participants is necessary to increase the use
      of effective measures, and subsequently prevent or reduce injuries in sports.
      OBJECTIVE: The evidence-based Wintersportklaar online intervention has been
      developed to stimulate injury preventive behavior among skiers and snowboarders.
      In this article, the design of the effectiveness study will be described.
      METHODS: A randomized controlled trial with a follow-up period of four months
      during the winter sport season will be conducted. The participants consist of
      inexperienced skiers and snowboarders. At baseline, skiers and snowboarders in
      the intervention and control groups are asked to report the injury preventive
      measures they usually take during their preparation for their winter sport
      holiday. One and three months after baseline, skiers and snowboarders are asked
      to report retrospectively in detail what measures they took regarding injury
      prevention during their current winter sport preparation and winter sport
      holiday. Descriptive analyses (mean, standard deviation, frequency, range) are
      conducted for the different baseline variables in both study groups. To evaluate
      the success of the randomization, baseline values are analyzed for differences
      between the intervention and control groups (chi square, independent T tests
      and/or Mann-Whitney test). Chi square tests and/or logistic regression analyses
      are used to analyze behavioral change according to the intention to treat
      principle (as initially assigned). RESULTS: The project was funded in 2016 and
      enrolment was completed in 2017. Data analysis is currently under way and the
      first results are expected to be submitted for publication in 2018. CONCLUSIONS:
      To combat the negative side effects of sports participation, the use of injury
      preventive measures is desirable. As the use of injury prevention is usually not
      compulsory in skiing and snowboarding, a behavioral change is necessary to
      increase the use of effective injury preventive measures in winter sports. TRIAL
      REGISTRATION: Dutch Trial Registry NTR6233;
      http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=6233 (Archived by
      WebCite at  http://www.webcitation.org/6wXZPzjUi).

PMID- 29343461
TI  - Effects of Psychiatric Comorbidity in Immune-Mediated Inflammatory Disease:
      Protocol for a Prospective Study.
AB  - BACKGROUND: Immune-mediated inflammatory diseases (IMID), such as inflammatory
      bowel disease (IBD), multiple sclerosis (MS), and rheumatoid arthritis (RA), are
      highly prevalent in Canada and the United States and result in substantial
      personal and societal burden. The prevalence of psychiatric comorbidities,
      primarily depression and anxiety, in IMID exceeds those in the general population
      by two- to threefold, but remains underdiagnosed and undertreated. Furthermore,
      the effects of psychiatric comorbidity on IMID are not well understood.
      OBJECTIVE: The objectives of this study were (1) to compare health-related
      quality of life and work ability in persons with IMID and psychiatric comorbidity
      with those of persons with IMID without psychiatric comorbidity and with those of
      persons with depression and anxiety disorders alone, and (2) to validate existing
      case identification tools for depression and anxiety in persons with IMID to
      facilitate improved identification of depression and anxiety by clinicians. To
      achieve these objectives, we designed a prospective 3-year longitudinal study. In
      this paper, we aim to describe the study rationale and design and the
      characteristics of study participants. METHODS: Between November 2014 and July
      2016, we recruited 982 individuals from multiple clinic and community sources; 18
      were withdrawn due to protocol violations. RESULTS: The final study sample
      included 247 participants with IBD, 255 with MS, 154 with RA, and 308 with
      depression or anxiety. The majority were white, with the proportion ranging from
      85.4% (IBD [210/246]; MS [217/254]) to 74.5% (114/153, RA; P=.01). There was a
      female predominance in all groups, which was highest in the RA cohort (84.4%,
      130/154) and least marked in the IBD cohort (62.7%, 155/247). Participants with
      depression or anxiety were more likely to be single (36.0%, 111/308) than
      participants in any other group (11.8% [30/255]-22.7% [56/247], P<.001).
      CONCLUSIONS: This paper presents the rationale for this study, describes study
      procedures, and characterizes the cohort enrolled. Ultimately, the aim is
      improved care for individuals affected by IMID.

PMID- 29343463
TI  - The Impact of mHealth Interventions: Systematic Review of Systematic Reviews.
AB  - BACKGROUND: Mobile phone usage has been rapidly increasing worldwide. mHealth
      could efficiently deliver high-quality health care, but the evidence supporting
      its current effectiveness is still mixed. OBJECTIVE: We performed a systematic
      review of systematic reviews to assess the impact or effectiveness of mobile
      health (mHealth) interventions in different health conditions and in the
      processes of health care service delivery. METHODS: We used a common search
      strategy of five major scientific databases, restricting the search by
      publication date, language, and parameters in methodology and content.
      Methodological quality was evaluated using the Measurement Tool to Assess
      Systematic Reviews (AMSTAR) checklist. RESULTS: The searches resulted in a total
      of 10,689 articles. Of these, 23 systematic reviews (371 studies; more than
      79,665 patients) were included. Seventeen reviews included studies performed in
      low- and middle-income countries. The studies used diverse mHealth interventions,
      most frequently text messaging (short message service, SMS) applied to different
      purposes (reminder, alert, education, motivation, prevention). Ten reviews were
      rated as low quality (AMSTAR score 0-4), seven were rated as moderate quality
      (AMSTAR score 5-8), and six were categorized as high quality (AMSTAR score 9-11).
      A beneficial impact of mHealth was observed in chronic disease management,
      showing improvement in symptoms and peak flow variability in asthma patients,
      reducing hospitalizations and improving forced expiratory volume in 1 second;
      improving chronic pulmonary diseases symptoms; improving heart failure symptoms,
      reducing deaths and hospitalization; improving glycemic control in diabetes
      patients; improving blood pressure in hypertensive patients; and reducing weight
      in overweight and obese patients. Studies also showed a positive impact of SMS
      reminders in improving attendance rates, with a similar impact to phone call
      reminders at reduced cost, and improved adherence to tuberculosis and human
      immunodeficiency virus therapy in some scenarios, with evidence of decrease of
      viral load. CONCLUSIONS: Although mHealth is growing in popularity, the evidence
      for efficacy is still limited. In general, the methodological quality of the
      studies included in the systematic reviews is low. For some fields, its impact is
      not evident, the results are mixed, or no long-term studies exist. Exceptions
      include the moderate quality evidence of improvement in asthma patients,
      attendance rates, and increased smoking abstinence rates. Most studies were
      performed in high-income countries, implying that mHealth is still at an early
      stage of development in low-income countries.

PMID- 29343464
TI  - Cardiorespiratory Fitness, Coronary Artery Calcium, and Cardiovascular Disease
      Events in a Cohort of Generally Healthy Middle-Age Men: Results From the Cooper
      Center Longitudinal Study.
AB  - BACKGROUND: A robust literature demonstrates that coronary artery calcification
      (CAC) and cardiorespiratory fitness (CRF) are independent predictors of
      cardiovascular disease (CVD) events. Much less is known about the joint
      associations of CRF and CAC with CVD risk. In the setting of high CAC, high
      versus low CRF has been associated with decreased CVD events. The goal of this
      study was to assess the effect of continuous levels of CRF on CVD risk in the
      setting of increasing CAC burden. METHODS: We studied 8425 men without clinical
      CVD who underwent preventive medicine examinations that included an objective
      measurement of CRF and CAC between 1998 and 2007. There were 383 CVD events
      during an average follow-up of 8.4 years. Parametric proportional hazards
      regression models based on a Gompertz mortality rule were used to estimate total
      CVD incidence rates at 70 years of age as well as hazard ratios for the included
      covariates. RESULTS: CVD events increased with increasing CAC and decreased with
      increasing CRF. Adjusting for CAC level (scores of 0, 1-99, 100-399, and >=400),
      for each additional MET of fitness, there was an 11% lower risk for CVD events
      (hazard ratio, 0.89; 95% confidence interval, 0.84-0.94). When CAC and CRF were
      considered together, there was a strong association between continuous CRF and
      CVD incidence rates in all CAC groups. CONCLUSIONS: In a large cohort of
      generally healthy men, there is an attenuation of CVD risk at all CAC levels with
      higher CRF.

PMID- 29343466
TI  - Long-term cardiovascular prognosis after transient ischemic attack: Associated
      predictors.
AB  - OBJECTIVE: To determine long-term cardiovascular risk after TIA and to identify
      the factors associated with increased risk. METHODS: This was a prospective
      observational registry of TIA patients admitted to the emergency room of our
      tertiary stroke center from June 2006 to January 2016. New vascular events (NVEs)
      were recorded from 3 months after TIA onset until June 2017, including both
      stroke and nonstroke events (coronary and peripheral disease). We registered TIA
      etiology, age, sex, vascular risk factors, radiologic data, and clinical TIA
      features and analyzed these variables in relation to NVE long-term risk. RESULTS:
      In total, 676 patients 71.7 +/- 13.7 years of age were included, with a mean
      follow-up of 48.8 +/- 32.7 months. An NVE was detected in 173 patients (25.6%)
      without significant differences between event types (p = 0.84). Univariate
      analysis associated NVEs with etiologic subgroup, male sex, diabetes mellitus,
      hypertension, previous vascular disease, duration and clinical features of TIA,
      and signs of acute infarction. Multivariable analysis showed an independent
      association of NVEs with etiologic TIA subgroup, signs of acute infarction, and
      duration of TIA symptoms. Large artery atherosclerosis and cardioaortic embolism
      had the highest NVE risk, with a slightly higher percentage of nonstroke events.
      The small artery disease subgroup had the lowest NVE risk, with a higher
      percentage of stroke events. CONCLUSIONS: Etiology subgroup was the main factor
      determining high long-term risk of vascular events in patients with TIA. Large
      artery atherosclerosis carried the highest vascular risk, both nonstroke and
      stroke, followed by cardioaortic embolism.

PMID- 29343465
TI  - Sex differences in cerebrovascular pathologies on FLAIR in cognitively unimpaired
      elderly.
AB  - OBJECTIVE: To examine sex differences in cerebrovascular pathologies (CVPs) as
      seen on fluid-attenuated inversion recovery (FLAIR) MRI and in cardiovascular and
      metabolic risk factors in a population-based cognitively unimpaired cohort and to
      examine whether sex is independently associated with FLAIR findings after
      accounting for differences in important midlife risk factors. METHODS: We
      identified 1,301 cognitively normal participants (663 men and 638 women) enrolled
      in the Mayo Clinic Study of Aging (age >=70 years) who had FLAIR MRI and
      ascertained total burden of white matter (WM) hyperintensities (WMH), subcortical
      infarctions, and cortical infarctions. We compared CVPs and midlife and late-life
      vascular risk factors between men and women. We fit regression models with each
      CVP as an outcome, treating age, sex, and midlife risk factors as predictors.
      RESULTS: Women had significantly greater WMH volume relative to their WM volume
      compared to men (2.8% vs 2.4% of WM, p < 0.001), while men had a greater
      frequency of cortical infarctions compared to women (9% vs 4%, p < 0.001).
      Subcortical infarctions were equally common in men and women (20%). In regression
      modeling after adjustment for WM volume, the mean WMH volume difference between
      men and women was of the same magnitude as a 7-year difference in age. In
      contrast, men had 2.2-greater relative odds of having a cortical infarction
      compared to women. These sex differences persisted even after adjustment for
      midlife vascular risk factors. CONCLUSIONS: There were important sex differences
      in CVP findings on FLAIR in cognitively unimpaired elderly. Understanding these
      sex differences could aid in the development of sex-specific preventive
      strategies.

PMID- 29343467
TI  - Hearing impairment in patients with myotonic dystrophy type 2.
AB  - OBJECTIVE: To systematically assess auditory characteristics of a large cohort of
      patients with genetically confirmed myotonic dystrophy type 2 (DM2). METHODS:
      Patients with DM2 were included prospectively in an international cross-sectional
      study. A structured interview about hearing symptoms was held. Thereafter,
      standardized otologic examination, pure tone audiometry (PTA; 0.25, 0.5, 1, 2, 4,
      and 8 kHz), speech audiometry, tympanometry, acoustic middle ear muscle reflexes,
      and brainstem auditory evoked potentials (BAEP) were performed. The ISO 7029
      standard was used to compare the PTA results with established hearing thresholds
      of the general population according to sex and age. RESULTS: Thirty-one Dutch and
      25 French patients with DM2 (61% female) were included with a mean age of 57
      years (range 31-78). The median hearing threshold of the DM2 cohort was higher
      for all measured frequencies, compared to the 50th percentile of normal (p <
      0.001). Hearing impairment was mild in 39%, moderate in 21%, and severe in 2% of
      patients with DM2. The absence of an air-bone gap with PTA, concordant results of
      speech audiometry with PTA, and normal findings of BAEP suggest that the
      sensorineural hearing impairment is located in the cochlea. A significant
      correlation was found between hearing impairment and age, even when corrected for
      presbycusis. CONCLUSIONS: Cochlear sensorineural hearing impairment is a frequent
      symptom in patients with DM2, suggesting an early presbycusis. Therefore, we
      recommend informing about hearing impairment and readily performing audiometry
      when hearing impairment is suspected in order to propose early hearing
      rehabilitation with hearing aids when indicated.

PMID- 29343468
TI  - Onabotulinum toxin-A injections for sleep bruxism: A double-blind, placebo
      controlled study.
AB  - OBJECTIVES: To test the safety and efficacy of onabotulinum toxin-A (BoNT-A)
      injections into the masseter and temporalis muscles in patients with symptomatic
      sleep bruxism. METHODS: Participants 18 to 85 years old with clinically diagnosed
      sleep bruxism confirmed by polysomnography were enrolled in this randomized,
      placebo-controlled, 1:1, parallel-design trial with open-label extension.
      Participants were injected with BoNT-A 200 units (60 into each masseter and 40
      into each temporalis) or placebo and were evaluated at 4 to 8 weeks after the
      initial treatment visit. The primary efficacy endpoint was clinical global
      impression (CGI), and the secondary efficacy endpoint was a visual analog scale
      (VAS) of change in bruxism and in pain at 4 to 8 weeks after injection.
      Exploratory endpoints included modified Montreal Bruxism Questionnaire, Headache
      Impact Test-6, total Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale,
      Self-Rated Anxiety Scale, and polysomnography data, including EMG recordings of
      the masseter and temporalis muscle bruxing events. Adverse events were recorded.
      RESULTS: Thirty-one participants were recruited and 23 were randomized (19
      female, age 47.4 +/- 16.9 years). All 13 randomized to BoNT-A and 9 of 10
      randomized to placebo completed the study. CGI (p < 0.05) and VAS of change (p <
      0.05) favored the BoNT-A group. None of the exploratory endpoints changed
      significantly, but total sleep time and number/duration of bruxing episodes
      favored the BoNT-A group. Two participants randomized to BoNT-A reported a
      cosmetic change in their smile. No dysphagia or masticatory adverse events were
      reported. CONCLUSIONS: BoNT-A effectively and safely improved sleep bruxism in
      this placebo-controlled pilot trial. A large multicenter trial is needed to
      confirm these encouraging data. CLINICALTRIALSGOV IDENTIFIER: NTC00908050. CLASS
      OF EVIDENCE: This study provides Class II evidence that botulinum injections into
      the masseter and temporalis muscles improve subjective bruxism and painful
      symptoms associated with sleep bruxism.

PMID- 29343469
TI  - Entrustable professional activities: A useful concept for neurology education.
AB  - Medical education is currently undergoing a paradigm shift from process-based to
      competency-based education, focused on measuring the desired competence of a
      physician. In an attempt to improve the assessment framework used for medical
      education, the concept of entrustable professional activities (EPAs) has gained
      traction. EPAs are defined as professional activities that can be entrusted to an
      individual in a clinical context. The Association of American Medical Colleges
      (AAMC) defined a set of 13 such EPAs to define the core of what all students
      should be able to do on day 1 of residency, regardless of specialty choice. The
      AAMC is currently piloting these EPAs with 10 medical schools to determine if
      EPAs can be used as a way to observe, measure, and entrust medical students with
      core clinical activities by the end of the clinical immersion experiences of the
      third year. The specialty of pediatrics is piloting the use of specialty-specific
      EPAs at 5 medical schools to assess readiness for transitions from medical school
      into pediatric residency training and practice. To date, no neurology-specific
      EPAs have been published for use in neurology clerkships or neurology
      residencies. This article introduces the concept of EPAs in the context of
      competency-based medical education and describes how EPAs might be relevant and
      applicable in neurologic education across the continuum. The Undergraduate
      Education Subcommittee of the American Academy of Neurology advocates for a
      proactive approach to incorporating core EPAs in undergraduate medical education
      and to considering an EPA-based specialty-specific assessment framework for
      neurology.

PMID- 29343471
TI  - Infantile-onset hand dystonia with intellectual disability: Clues to ARX
      mutations.

PMID- 29343470
TI  - Cognition in multiple sclerosis: State of the field and priorities for the
      future.
AB  - Cognitive decline is recognized as a prevalent and debilitating symptom of
      multiple sclerosis (MS), especially deficits in episodic memory and processing
      speed. The field aims to (1) incorporate cognitive assessment into standard
      clinical care and clinical trials, (2) utilize state-of-the-art neuroimaging to
      more thoroughly understand neural bases of cognitive deficits, and (3) develop
      effective, evidence-based, clinically feasible interventions to prevent or treat
      cognitive dysfunction, which are lacking. There are obstacles to these goals. Our
      group of MS researchers and clinicians with varied expertise took stock of the
      current state of the field, and we identify several important practical and
      theoretical challenges, including key knowledge gaps and methodologic limitations
      related to (1) understanding and measurement of cognitive deficits, (2)
      neuroimaging of neural bases and correlates of deficits, and (3) development of
      effective treatments. This is not a comprehensive review of the extensive
      literature, but instead a statement of guidelines and priorities for the field.
      For instance, we provide recommendations for improving the scientific basis and
      methodologic rigor for cognitive rehabilitation research. Toward this end, we
      call for multidisciplinary collaborations toward development of biologically
      based theoretical models of cognition capable of empirical validation and
      evidence-based refinement, providing the scientific context for effective
      treatment discovery.

PMID- 29343472
TI  - Clinical spectrum of hemiplegic migraine and chances of finding a pathogenic
      mutation.
AB  - OBJECTIVE: To investigate whether the clinical characteristics of patients with
      hemiplegic migraine with and without autosomal dominant mutations in CACNA1A,
      ATP1A2, or SCN1A differ, and whether the disease may be caused by mutations in
      other genes. METHODS: We compared the clinical characteristics of 208 patients
      with familial (n = 199) or sporadic (n = 9) hemiplegic migraine due to a mutation
      in CACNA1A, ATP1A2, or SCN1A with those of 73 patients with familial (n = 49) or
      sporadic (n = 24) hemiplegic migraine without a mutation in these genes. In
      addition, 47 patients (familial: n = 33; sporadic: n = 14) without mutations in
      CACNA1A, ATP1A2, or SCN1A were scanned for mutations in novel genes using whole
      exome sequencing. RESULTS: Patients with mutations in CACNA1A, ATP1A2, or SCN1A
      had a lower age at disease onset, larger numbers of affected family members, and
      more often attacks (1) triggered by mild head trauma, (2) with extensive motor
      weakness, and (3) with brainstem features, confusion, and brain edema. Mental
      retardation and progressive ataxia were exclusively found in patients with a
      mutation. Whole exome sequencing failed to identify pathogenic mutations in new
      genes. CONCLUSIONS: Most patients with hemiplegic migraine without a mutation in
      CACNA1A, ATP1A2, or SCN1A display a mild phenotype that is more akin to that of
      common (nonhemiplegic) migraine. A major fourth autosomal dominant gene for
      hemiplegic migraine remains to be identified. Our observations might guide
      physicians in selecting patients for mutation screening and in providing adequate
      genetic counseling.

PMID- 29343473
TI  - Smoking affects the interferon beta treatment response in multiple sclerosis.
AB  - OBJECTIVE: To investigate whether smoking in patients with relapsing-remitting
      multiple sclerosis (RRMS) treated with interferon beta (IFN-beta) is associated
      with the relapse rate and whether there is an interaction between smoking and
      human leukocyte antigen (HLA)-DRB1*15:01, HLA-A*02:01, and the N
      acetyltransferase-1 (NAT1) variant rs7388368A. METHODS: DNA from 834 IFN-beta
      treated patients with RRMS from the Danish Multiple Sclerosis Biobank was
      extracted for genotyping. Information about relapses from 2 years before the
      start of treatment to either the end of treatment or the last follow-up visit was
      obtained from the Danish Multiple Sclerosis Treatment Register. Smoking
      information came from a comprehensive questionnaire. RESULTS: We found that the
      relapse rate in patients with RRMS during IFN-beta treatment was higher in
      smokers compared to nonsmokers, with an incidence rate ratio (IRR) of 1.20 (95%
      confidence interval [CI] 1.021-1.416, p = 0.027) and with an IRR increase of 27%
      per pack of cigarettes per day (IRR 1.27, 95% CI 1.056-1.537, p = 0.012). We
      found no association or interaction with HLA and the NAT1 variant. CONCLUSION: In
      this observational cohort study, we found that smoking is associated with
      increased relapse activity in patients with RRMS treated with IFN-beta, but we
      found no association or interaction with HLA or the NAT1 variant.

PMID- 29343475
TI  - Staff shortages force mental health trusts to cancel patient activities and close
      wards, says King's Fund.

PMID- 29343474
TI  - Doctors do not feel protected when things go wrong.

PMID- 29343476
TI  - Role of Macrophage Socs3 in the Pathogenesis of Aortic Dissection.
AB  - BACKGROUND: Aortic dissection (AD) is a life-threatening medical emergency caused
      by the abrupt destruction of the intimomedial layer of the aortic walls. Given
      that previous studies have reported the involvement of proinflammatory cytokine
      interleukin-6 in AD pathogenesis, we investigated the role of signal transduction
      and activator of transcription 3 signaling, a downstream pathway of interleukin-6
      in macrophages in pathogenesis of AD. METHODS AND RESULTS: We characterized the
      pathological and molecular events triggered by aortic stress, which can lead to
      AD. Aortic stress on the suprarenal aorta because of infrarenal aorta stiffening
      and angiotensin II infusion for 1 week caused focal medial rupture at the
      branching point of the celiac trunk and superior mesenteric artery. This focal
      medial rupture healed in 6 weeks in wild-type (WT) mice, but progressed to AD in
      mice with macrophage-specific deletion of Socs3 gene (mSocs3-KO). mSocs3-KO mice
      showed premature activation of cell proliferation, an inflammatory response, and
      skewed differentiation of macrophages toward the tissue-destructive phenotype.
      Concomitantly, they showed aberrant phenotypic modulation of smooth muscle cells
      and transforming growth factor beta signaling, which are likely to participate in
      tissue repair. Human AD samples revealed signal transduction and activator of
      transcription 3 activation in adventitial macrophages adjacent to the site of
      tissue destruction. CONCLUSIONS: These findings suggest that AD development is
      preceded by focal medial rupture, in which macrophage Socs3 maintains proper
      inflammatory response and differentiation of SMCs, thus promoting fibrotic
      healing to prevent tissue destruction and AD development. Understanding the
      sequence of the pathological and molecular events preceding AD development will
      help predict and prevent AD development and progression.

PMID- 29343477
TI  - Role of ASIC3, Nav1.7 and Nav1.8 in electroacupuncture-induced analgesia in a
      mouse model of fibromyalgia pain.
AB  - BACKGROUND: The mechanisms underlying fibromyalgia (FM) pain are not understood.
      The US Food and Drug Administration has recommended three drugs for treating FM
      namely, pregabalin, duloxetine and milnacipran; however, these medications are
      associated with severe side effects. OBJECTIVE: To create a mouse model of FM
      pain using dual injections of acidic saline to cause mechanical hyperalgesia and
      test whether ASIC3, Nav1.7 and Nav1.8 are involved in this process and whether
      electroacupuncture (EA) can reverse these phenomena. METHODS: The FM model was
      established by injecting acidic saline twice into 40 ICR mice. The mice were
      assigned to subgroups (n=8 each) treated with different EA frequencies (2, 15 and
      50 Hz). ASIC3, Nav1.7 and Nav1.8 expression levels were measured by Western
      blotting and immunohistochemistry. RESULTS: Significant mechanical hyperalgesia
      was induced on day 8 in FM mice, which was reversed by 2, 15 and 50 Hz EA. ASIC3,
      Nav1.7 and Nav1.8 protein levels increased significantly in both the dorsal root
      ganglion and in the spinal cord of FM model mice. These changes were further
      attenuated by 2, 15 and 50 Hz EA. CONCLUSION: Reduced nociceptive ASIC3, Nav1.7
      and Nav1.8 proteins are involved in the preventive effects of EA against FM, and
      this series of molecules may represent targets for FM treatment.

PMID- 29343478
TI  - Treatment of gastrointestinal bleeding with idarucizumab in a patient receiving
      dabigatran.
AB  - PURPOSE: A case report describing use of idarucizumab for dabigatran reversal
      without the use of hemostatic agents in a patient who developed acute upper
      gastrointestinal (GI) bleeding while receiving triple antithrombotic therapy is
      presented. SUMMARY: A 77-year-old man with a complex cardiac history presented to
      the emergency room with chief complaints of black tarry stools and low blood
      pressures for 4 days. His past medical history included recent percutaneous
      coronary intervention (PCI) and drug-eluting stent (DES) placement, atrial
      fibrillation, hypertension, hyperlipidemia, coronary artery disease, coronary
      artery bypass graft surgery, stage 3 chronic kidney disease, and cholecystectomy.
      His triple antithrombotic therapy consisted of aspirin, clopidogrel, and
      dabigatran. The patient stated that his last dose of dabigatran was taken the
      night before. Serum dabigatran levels were not measured. Due to suspicion of
      acute upper GI bleeding, all antithrombotic agents were withheld. Treatment with
      idarucizumab, i.v. pantoprazole, and blood transfusion was ordered. An upper
      endoscopy was safely performed 24 hours later and revealed a minor Mallory-Weiss
      tear. The patient was discharged 48 hours later with prescriptions for acid
      suppressant and triple antithrombotic therapy; his melena had resolved before
      discharge. At 14-week follow-up, the patient reported that his cardiologist had
      deleted aspirin from his antithrombotic regimen. CONCLUSION: A patient who had
      recently undergone PCI and DES placement and was receiving aspirin, clopidogrel,
      and dabigatran for atrial fibrillation was successfully treated for acute GI
      bleeding with idarucizumab without the use of a hemostatic agent.

PMID- 29343480
TI  - Samiran Nundy: Tackling India's corruption.

PMID- 29343481
TI  - Should all patients be asked about their sexual orientation?

PMID- 29343479
TI  - Postsurgical prescriptions for opioid naive patients and association with
      overdose and misuse: retrospective cohort study.
AB  - OBJECTIVE: To quantify the effects of varying opioid prescribing patterns after
      surgery on dependence, overdose, or abuse in an opioid naive population. DESIGN:
      Retrospective cohort study. SETTING: Surgical claims from a linked medical and
      pharmacy administrative database of 37 651 619 commercially insured patients
      between 2008 and 2016. PARTICIPANTS: 1 015 116 opioid naive patients undergoing
      surgery. MAIN OUTCOME MEASURES: Use of oral opioids after discharge as defined by
      refills and total dosage and duration of use. The primary outcome was a composite
      of misuse identified by a diagnostic code for opioid dependence, abuse, or
      overdose. RESULTS: 568 612 (56.0%) patients received postoperative opioids, and a
      code for abuse was identified for 5906 patients (0.6%, 183 per 100 000 person
      years). Total duration of opioid use was the strongest predictor of misuse, with
      each refill and additional week of opioid use associated with an adjusted
      increase in the rate of misuse of 44.0% (95% confidence interval 40.8% to 47.2%,
      P<0.001), and 19.9% increase in hazard (18.5% to 21.4%, P<0.001), respectively.
      CONCLUSIONS: Each refill and week of opioid prescription is associated with a
      large increase in opioid misuse among opioid naive patients. The data from this
      study suggest that duration of the prescription rather than dosage is more
      strongly associated with ultimate misuse in the early postsurgical period. The
      analysis quantifies the association of prescribing choices on opioid misuse and
      identifies levers for possible impact.

PMID- 29343484
TI  - System to support patients with ongoing needs is "falling short on many fronts".

PMID- 29343482
TI  - PAR1 biased signaling is required for activated protein C in vivo benefits in
      sepsis and stroke.
AB  - Activated protein C (APC) cleaves protease-activated receptor 1 (PAR1) in vitro
      at R46 to initiate beneficial cell signaling; however, thrombin and APC can
      cleave at R41. To elucidate PAR1-dependent aspects of the pharmacologic in vivo
      mechanisms of APC, we generated C57BL/6 mouse strains carrying QQ41 or QQ46 point
      mutations in PAR1 (F2r gene). Using these strains, we determined whether or not
      recombinant murine signaling-selective APC mutants would reduce septic death or
      provide neuroprotection against ischemic stroke when mice carried PAR1-homozygous
      mutations that prevent cleavage at either R41 or R46. Intercrossing PAR1+/R46Q
      mice generated expected numbers of PAR1+/+, PAR1+/R46Q, and R46Q/R46Q offspring
      whereas intercrossing PAR1+/R41Q mice gave decreased R41Q/R41Q homozygotes
      (resembling intercrossing PAR1+/PAR1-knockout mice). QQ41-PAR1 and QQ46-PAR1
      brain endothelial cells showed the predicted retention or loss of cellular
      responses to thrombin receptor-activating peptide, thrombin, or APC for each PAR1
      mutation. In sepsis studies, exogenous APC reduced mortality from 50% to 10% in
      Escherichia coli-induced pneumonia for wild-type (Wt) PAR1 and QQ41-PAR1 mice (P
      < .01) but had no benefit for QQ46-PAR1 mice. In transient distal middle cerebral
      artery occlusion stroke studies, exogenous APC significantly reduced infarct
      size, edema, and neuronal apoptosis for Wt mice and QQ41-PAR1 mice but had no
      detectable benefits for mice carrying QQ46-PAR1. In functional studies of
      forelimb-asymmetry and foot-fault tests at 24 hours after stroke induction,
      signaling-selective APC was beneficial for Wt and QQ41-PAR1 mice but not QQ46
      PAR1 mice. These results support the concept that APC-induced, PAR1-dependent
      biased signaling following R46 cleavage is central to the in vivo benefits of
      APC.

PMID- 29343485
TI  - Criminal and professional sanctions impede honesty and improvement.

PMID- 29343483
TI  - NR4A1 and NR4A3 restrict HSC proliferation via reciprocal regulation of
      C/EBPalpha and inflammatory signaling.
AB  - Members of the NR4A subfamily of nuclear receptors have complex, overlapping
      roles during hematopoietic cell development and also function as tumor
      suppressors of hematologic malignancies. We previously identified NR4A1 and NR4A3
      (NR4A1/3) as functionally redundant suppressors of acute myeloid leukemia (AML)
      development. However, their role in hematopoietic stem cell (HSC) homeostasis
      remains to be disclosed. Using a conditional Nr4a1/Nr4a3 knockout mouse (CDKO),
      we show that codepletion of NR4A1/3 promotes acute changes in HSC homeostasis
      including loss of HSC quiescence, accumulation of oxidative stress, and DNA
      damage while maintaining stem cell regenerative and differentiation capacity.
      Molecular profiling of CDKO HSCs revealed widespread upregulation of genetic
      programs governing cell cycle and inflammation and an aberrant activation of the
      interferon and NF-kappaB signaling pathways in the absence of stimuli.
      Mechanistically, we demonstrate that NR4A1/3 restrict HSC proliferation in part
      through activation of a C/EBPalpha-driven antiproliferative network by directly
      binding to a hematopoietic-specific Cebpa enhancer and activating Cebpa
      transcription. In addition, NR4A1/3 occupy the regulatory regions of NF-kappaB
      regulated inflammatory cytokines, antagonizing the activation of NF-kappaB
      signaling. Taken together, our results reveal a novel coordinate control of HSC
      quiescence by NR4A1/3 through direct activation of C/EBPalpha and suppression of
      activation of NF-kappaB-driven proliferative inflammatory responses.

PMID- 29343487
TI  - Sixty seconds on . . . the Lansley diaries.

PMID- 29343488
TI  - Commentary: Let's talk about sex.

PMID- 29343486
TI  - Electronic cigarettes for smoking cessation.

PMID- 29343489
TI  - GMC should deal forcefully with repeatedly dishonest doctors.

PMID- 29343491
TI  - Mexicans head off spread of zoonotic tuberculosis.

PMID- 29343492
TI  - Boris Johnson is criticised for repeating claims that NHS will benefit from
      Brexit.

PMID- 29343493
TI  - CCG criticises NHS England after being ordered to cut GP funding.

PMID- 29343495
TI  - GMC erasure: it could have been me.

PMID- 29343496
TI  - Trump administration halts "evidence based" treatment database.

PMID- 29343494
TI  - Uncovering Genomic Regions Associated with Trypanosoma Infections in Wild
      Populations of the Tsetse Fly Glossina fuscipes.
AB  - Vector-borne diseases are responsible for > 1 million deaths every year but
      genomic resources for most species responsible for their transmission are
      limited. This is true for neglected diseases such as sleeping sickness (Human
      African Trypanosomiasis), a disease caused by Trypanosoma parasites vectored by
      several species of tseste flies within the genus Glossina We describe an
      integrative approach that identifies statistical associations between trypanosome
      infection status of Glossina fuscipes fuscipes (Gff) flies from Uganda, for which
      functional studies are complicated because the species cannot be easily
      maintained in laboratory colonies, and ~73,000 polymorphic sites distributed
      across the genome. Then, we identify candidate genes involved in Gff trypanosome
      susceptibility by taking advantage of genomic resources from a closely related
      species, G. morsitans morsitans (Gmm). We compiled a comprehensive transcript
      library from 72 published and unpublished RNAseq experiments of trypanosome
      infected and uninfected Gmm flies, and improved the current Gmm transcriptome
      assembly. This new assembly was then used to enhance the functional annotations
      on the Gff genome. As a consequence, we identified 56 candidate genes in the
      vicinity of the 18 regions associated with Trypanosoma infection status in Gff
      Twenty-nine of these genes were differentially expressed (DE) among parasite
      infected and uninfected Gmm, suggesting that their orthologs in Gff may correlate
      with disease transmission. These genes were involved in DNA regulation,
      neurophysiological functions, and immune responses. We highlight the power of
      integrating population and functional genomics from related species to enhance
      our understanding of the genetic basis of physiological traits, particularly in
      nonmodel organisms.

PMID- 29343497
TI  - Most medical practices are not parachutes: a citation analysis of practices felt
      by biomedical authors to be analogous to parachutes.
AB  - BACKGROUND: In a 2003 paper in BMJ, the authors made the tongue-in-cheek
      observation that there are no randomized controlled trials (RCTs) of parachutes.
      This paper has been widely read, cited and used to argue that RCTs are
      impractical or unnecessary for some medical practices. We performed a study to
      identify and evaluate claims that a medical practice is akin to a parachute.
      METHODS: Using Google Scholar, we identified all citations to the 2003 paper. We
      searched for claims that a specific practice was akin to a parachute. For each
      practice, we identified the desired outcome of the practice, and searched Google
      Scholar and ClinicalTrials.gov for RCTs that were conducted, ongoing, halted,
      planned or unpublished. RESULTS: Of 822 articles citing the original paper, 35
      (4.1%) argued that a medical practice was akin to a parachute. Eighteen of the 35
      (51%) concerned mortality or live birth, and 17 (49%) concerned a lesser outcome.
      For 22 practices (63%), we identified 1 or more RCTs: in 6 cases (27%), the
      trials showed a statistically significant benefit of the practice; in 5 (23%),
      the trials rejected the practice; in 5 (23%), the trials had mixed results; in 2
      (9%), the trials were halted; and in 4 (18%), the trials were ongoing. Effect
      size was calculated for 5 of the 6 practices for which RCTs gave positive
      results, and the absolute risk reduction ranged from 11% to 30.8%, corresponding
      to a number needed to treat of 3-9. INTERPRETATION: Although there is widespread
      interest regarding the BMJ paper arguing that randomized trials are not necessary
      for practices of clear benefit, there are few analogies in medicine. Most
      parachute analogies in medicine are inappropriate, incorrect or misused.

PMID- 29343498
TI  - The GPR120 agonist TUG-891 promotes metabolic health by stimulating mitochondrial
      respiration in brown fat.
AB  - Brown adipose tissue (BAT) activation stimulates energy expenditure in human
      adults, which makes it an attractive target to combat obesity and related
      disorders. Recent studies demonstrated a role for G protein-coupled receptor 120
      (GPR120) in BAT thermogenesis. Here, we investigated the therapeutic potential of
      GPR120 agonism and addressed GPR120-mediated signaling in BAT We found that
      activation of GPR120 by the selective agonist TUG-891 acutely increases fat
      oxidation and reduces body weight and fat mass in C57Bl/6J mice. These effects
      coincided with decreased brown adipocyte lipid content and increased nutrient
      uptake by BAT, confirming increased BAT activity. Consistent with these
      observations, GPR120 deficiency reduced expression of genes involved in nutrient
      handling in BAT Stimulation of brown adipocytes in vitro with TUG-891 acutely
      induced O2 consumption, through GPR120-dependent and GPR120-independent
      mechanisms. TUG-891 not only stimulated GPR120 signaling resulting in
      intracellular calcium release, mitochondrial depolarization, and mitochondrial
      fission, but also activated UCP1. Collectively, these data suggest that
      activation of brown adipocytes with the GPR120 agonist TUG-891 is a promising
      strategy to increase lipid combustion and reduce obesity.

PMID- 29343499
TI  - A Population Phylogenetic View of Mitochondrial Heteroplasmy.
AB  - The mitochondrion has recently emerged as an active player in myriad cellular
      processes. Additionally, it was recently shown that >200 diseases are known to be
      linked to variants in mitochondrial DNA or in nuclear genes interacting with
      mitochondria. This has reinvigorated interest in its biology and population
      genetics. Mitochondrial heteroplasmy, or genotypic variation of mitochondria
      within an individual, is now understood to be common in humans and important in
      human health. However, it is still not possible to make quantitative predictions
      about the inheritance of heteroplasmy and its proliferation within the body,
      partly due to the lack of an appropriate model. Here, we present a population
      genetic framework for modeling mitochondrial heteroplasmy as a process that
      occurs on an ontogenetic phylogeny, with genetic drift and mutation changing
      heteroplasmy frequencies during the various developmental processes represented
      in the phylogeny. Using this framework, we develop a Bayesian inference method
      for inferring rates of mitochondrial genetic drift and mutation at different
      stages of human life. Applying the method to previously published heteroplasmy
      frequency data, we demonstrate a severe effective germline bottleneck comprised
      of the cumulative genetic drift occurring between the divergence of germline and
      somatic cells in the mother, and the separation of germ layers in the offspring.
      Additionally, we find that the two somatic tissues we analyze here undergo tissue
      specific bottlenecks during embryogenesis, less severe than the effective
      germline bottleneck, and that these somatic tissues experience little additional
      genetic drift during adulthood. We conclude with a discussion of possible
      extensions of the ontogenetic phylogeny framework and its possible applications
      to other ontogenetic processes in addition to mitochondrial heteroplasmy.

PMID- 29343500
TI  - Cbfbeta2 controls differentiation of and confers homing capacity to prethymic
      progenitors.
AB  - Multipotent hematopoietic progenitors must acquire thymus-homing capacity to
      initiate T lymphocyte development. Despite its importance, the transcriptional
      program underlying this process remains elusive. Cbfbeta forms transcription
      factor complexes with Runx proteins, and here we show that Cbfbeta2, encoded by
      an RNA splice variant of the Cbfb gene, is essential for extrathymic
      differentiation of T cell progenitors. Furthermore, Cbfbeta2 endows extrathymic
      progenitors with thymus-homing capacity by inducing expression of the principal
      thymus-homing receptor, Ccr9. This occurs via direct binding of Cbfbeta2 to cell
      type-specific enhancers, as is observed in Rorgammat induction during
      differentiation of lymphoid tissue inducer cells by activation of an intronic
      enhancer. As in mice, an alternative splicing event in zebrafish generates a
      Cbfbeta2-specific mRNA, important for ccr9 expression. Thus, despite
      phylogenetically and ontogenetically variable sites of origin of T cell
      progenitors, their robust thymus-homing capacity is ensured by an evolutionarily
      conserved mechanism emerging from functional diversification of Runx
      transcription factor complexes by acquisition of a novel splice variant.

PMID- 29343502
TI  - Taking deterministic control of membrane protein monomer-dimer measurements.

PMID- 29343501
TI  - Sequential BMP7/TGF-beta1 signaling and microbiota instruct mucosal Langerhans
      cell differentiation.
AB  - Mucosal Langerhans cells (LCs) originate from pre-dendritic cells and monocytes.
      However, the mechanisms involved in their in situ development remain unclear.
      Here, we demonstrate that the differentiation of murine mucosal LCs is a two-step
      process. In the lamina propria, signaling via BMP7-ALK3 promotes translocation of
      LC precursors to the epithelium. Within the epithelium, TGF-beta1 finalizes LC
      differentiation, and ALK5 is crucial to this process. Moreover, the local
      microbiota has a major impact on the development of mucosal LCs, whereas LCs in
      turn maintain mucosal homeostasis and prevent tissue destruction. These results
      reveal the differential and sequential role of TGF-beta1 and BMP7 in LC
      differentiation and highlight the intimate interplay of LCs with the microbiota.

PMID- 29343503
TI  - In the Histone Zone: The Mighty Eraser.

PMID- 29343504
TI  - Canonical and Noncanonical Actions of Arabidopsis Histone Deacetylases in
      Ribosomal RNA Processing.
AB  - Ribosome biogenesis is a fundamental process required for all cellular
      activities. Histone deacetylases play critical roles in many biological processes
      including transcriptional repression and rDNA silencing. However, their function
      in pre-rRNA processing remains poorly understood. Here, we discovered a
      previously uncharacterized role of Arabidopsis thaliana histone deacetylase HD2C
      in pre-rRNA processing via both canonical and noncanonical manners. HD2C
      interacts with another histone deacetylase HD2B and forms homo- and/or hetero
      oligomers in the nucleolus. Depletion of HD2C and HD2B induces a ribosome
      biogenesis deficient phenotype and aberrant accumulation of 18S pre-rRNA
      intermediates. Our genome-wide analysis revealed that HD2C binds and represses
      the expression of key genes involved in ribosome biogenesis. Using RNA
      immunoprecipitation and sequencing, we further uncovered a noncanonical mechanism
      of HD2C directly associating with pre-rRNA and small nucleolar RNAs to regulate
      rRNA methylation. Together, this study reveals a multifaceted role of HD2C in
      ribosome biogenesis and provides mechanistic insights into how histone
      deacetylases modulate rRNA maturation at the transcriptional and
      posttranscriptional levels.

PMID- 29343506
TI  - How to use... Procalcitonin.
AB  - Diagnosing bacterial infection in the unwell or febrile child is a common
      challenge faced by all paediatricians. Despite the advent of novel molecular
      techniques, there is ongoing need for diagnostic assays with adequate performance
      and turnaround time to facilitate safe clinical decision-making when bacterial
      sepsis is suspected, such as whether to commence empirical treatment with
      antibiotics. Procalcitonin is an established marker of infection that has a
      potential role in the diagnosis and exclusion of serious or invasive bacterial
      infection in neonates and children. Although enthusiastically adopted in many
      countries and institutions, national guidance in the UK does not yet support its
      routine use. This article reviews the relevant literature on the use of
      procalcitonin measurement in common paediatric clinical scenarios.

PMID- 29343505
TI  - Revisiting Criteria for Plant MicroRNA Annotation in the Era of Big Data.
AB  - MicroRNAs (miRNAs) are ~21-nucleotide-long regulatory RNAs that arise from
      endonucleolytic processing of hairpin precursors. Many function as essential
      posttranscriptional regulators of target mRNAs and long noncoding RNAs. Alongside
      miRNAs, plants also produce large numbers of short interfering RNAs (siRNAs),
      which are distinguished from miRNAs primarily by their biogenesis (typically
      processed from long double-stranded RNA instead of single-stranded hairpins) and
      functions (typically via roles in transcriptional regulation instead of
      posttranscriptional regulation). Next-generation DNA sequencing methods have
      yielded extensive data sets of plant small RNAs, resulting in many miRNA
      annotations. However, it has become clear that many miRNA annotations are
      questionable. The sheer number of endogenous siRNAs compared with miRNAs has been
      a major factor in the erroneous annotation of siRNAs as miRNAs. Here, we provide
      updated criteria for the confident annotation of plant miRNAs, suitable for the
      era of "big data" from DNA sequencing. The updated criteria emphasize replication
      and the minimization of false positives, and they require next-generation
      sequencing of small RNAs. We argue that improved annotation systems are needed
      for miRNAs and all other classes of plant small RNAs. Finally, to illustrate the
      complexities of miRNA and siRNA annotation, we review the evolution and functions
      of miRNAs and siRNAs in plants.

PMID- 29343508
TI  - Circular RNA VMA21 protects against intervertebral disc degeneration through
      targeting miR-200c and X linked inhibitor-of-apoptosis protein.
AB  - OBJECTIVES: Circular RNAs (circRNAs) have been proven to function as competing
      endogenous RNAs to interact with microRNAs (miRNAs) and influence the expression
      of miRNA target mRNAs. In this study, we investigated whether circRNAs could act
      as competing endogenous RNAs to regulate the pathological process of
      intervertebral disc degeneration (IVDD). METHODS: The role and mechanism of a
      circRNA, circVMA21, in IVDD were explored in nucleus pulposus (NP) cells and
      degenerative NP tissues from patients and rat models. The interaction between
      circVMA21 and miR-200c as well as the target mRNA, X linked inhibitor-of
      apoptosis protein (XIAP), was examined. RESULTS: The decreased expression of XIAP
      in the inflammatory cytokines-treated NP cells and the degenerative NP tissues
      was directly associated with excessive apoptosis and imbalance between anabolic
      and catabolic factors of extracellular matrix. miR-200c regulated NP cell
      viability and functions through inhibiting XIAP. circVMA21 acted as a sponge of
      miR-200c and functioned in NP cells through targeting miR-200c and XIAP.
      Intradiscal injection of circVMA21 alleviated IVDD in the rat model. CONCLUSIONS:
      CircVMA21 could alleviate inflammatory cytokines-induced NP cell apoptosis and
      imbalance between anabolism and catabolism of extracellular matrix through miR
      200c-XIAP pathway. It provides a potentially effective therapeutic strategy for
      IVDD.

PMID- 29343507
TI  - Early and sustained efficacy with apremilast monotherapy in biological-naive
      patients with psoriatic arthritis: a phase IIIB, randomised controlled trial
      (ACTIVE).
AB  - OBJECTIVE: Evaluate apremilast efficacy across various psoriatic arthritis (PsA)
      manifestations beginning at week 2 in biological-naive patients with PsA.
      METHODS: Patients were randomised (1:1) to apremilast 30 mg twice daily or
      placebo. At week 16, patients whose swollen and tender joint counts had not
      improved by >=10% were eligible for early escape. At week 24, all patients
      received apremilast through week 52. RESULTS: Among 219 randomised patients
      (apremilast: n=110; placebo: n=109), a significantly greater American College of
      Rheumatology 20 response at week 16 (primary outcome) was observed with
      apremilast versus placebo (38.2% (42/110) vs 20.2% (22/109); P=0.004); response
      rates at week 2 (first assessment) were 16.4% (18/110) versus 6.4% (7/109)
      (P=0.025). Improvements in other efficacy outcomes, including 28-joint count
      Disease Activity Score (DAS-28) using C reactive protein (CRP), swollen joint
      count, Health Assessment Questionnaire-Disability Index (HAQ-DI), enthesitis and
      morning stiffness severity, were observed with apremilast at week 2. At week 16,
      apremilast significantly reduced PsA disease activity versus placebo, with
      changes in DAS-28 (CRP) (P<0.0001), HAQ-DI (P=0.023) and Gladman Enthesitis Index
      (P=0.001). Improvements were maintained with continued treatment through week 52.
      Over 52 weeks, apremilast's safety profile was consistent with prior phase 3
      studies in psoriasis and PsA. During weeks 0-24, the incidence of protocol
      defined diarrhoea was 11.0% (apremilast) and 8.3% (placebo); serious adverse
      event rates were 2.8% (apremilast) and 4.6% (placebo). CONCLUSIONS: In biological
      naive patients with PsA, onset of effect with apremilast was observed at week 2
      and continued through week 52. The safety profile was consistent with previous
      reports. TRIAL REGISTRATION NUMBER: NCT01925768; Results.

PMID- 29343511
TI  - Response to: 'Remission or low disease activity as a target in systemic lupus
      erythematosus' by Ugarte-Gil et al.

PMID- 29343510
TI  - Limited radiographic progression and sustained reductions in MRI inflammation in
      patients with axial spondyloarthritis: 4-year imaging outcomes from the RAPID
      axSpA phase III randomised trial.
AB  - OBJECTIVES: To report 4-year imaging outcomes in the RAPID-axSpA (NCT01087762)
      study of patients with ankylosing spondylitis (AS) and non-radiographic axial
      spondyloarthritis (nr-axSpA), treated with certolizumab pegol (CZP). METHODS:
      This phase III, randomised trial was placebo-controlled and double-blind to week
      24, dose-blind to week 48 and open-label to week 204. Patients fulfilling the
      Assessment of Spondyloarthritis International Society (ASAS) axSpA criteria with
      active disease were stratified (AS/nr-axSpA) according to the modified New York
      (mNY) criteria at randomisation. Spinal radiographs were assessed using the
      modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). MRI inflammation used
      the Spondyloarthritis Research Consortium of Canada (SPARCC) score for sacroiliac
      joints (SIJ) and the Berlin spinal score (remission defined as SPARCC <2 and
      Berlin <=2, respectively). RESULTS: MRI improvements from baseline (BL) to week
      12 were maintained to week 204 (SPARCC BL: AS=8.5, nr-axSpA=7.5; SPARCC week 204:
      AS=1.3, nr-axSpA=2.4; Berlin BL: AS=7.4, nr-axSpA=4.4; Berlin week 204: AS=2.6,
      nr-axSpA=1.9). 66.7% of patients with AS and 69.6% of patients with nr-axSpA with
      BL SPARCC scores >=2, and 65.4% of patients with AS and 57.3% of patients with nr
      axSpA with BL Berlin score >2, achieved remission at week 204. Mean mSASSS change
      in AS from BL to week 204 was 0.98 (95% CI 0.34, 1.63); 0.67 (95% CI 0.21,1.13)
      from BL to week 96; and 0.31 (95% CI 0.02,0.60) from week 96 to week 204.
      Corresponding nr-axSpA changes were 0.06 (95% CI -0.17,0.28), -0.01 (95% CI 
      0.19,0.17) and 0.07 (95% CI -0.07,0.20). 4.5% of patients with nr-axSpA fulfilled
      the mNY criteria at week 204, while 4.3% of patients with AS no longer did so.
      CONCLUSIONS: In patients with CZP-treated axSpA, rapid decreases in spinal and
      SIJ MRI inflammation were maintained to week 204. Overall, 4-year spinal
      progression was low, with less progression during years 2-4 than 0-2.
      Radiographic SIJ grading changes demonstrated limited progression. TRIAL
      REGISTRATION NUMBER: NCT01087762; Post-results.

PMID- 29343509
TI  - Efficacy and safety of tregalizumab in patients with rheumatoid arthritis and an
      inadequate response to methotrexate: results of a phase IIb, randomised, placebo
      controlled trial.
AB  - OBJECTIVE: To evaluate the efficacy, biological activity and safety of
      tregalizumab in patients with active rheumatoid arthritis (RA) and an inadequate
      response to methotrexate (MTX). METHODS: 321 patients were randomised (1:1:1:1)
      to placebo or tregalizumab 25, 100 or 200 mg once-weekly subcutaneously in
      addition to MTX treatment. Responders at week 12 continued the same treatment,
      and non-responders at week 12 were escalated to the next higher tregalizumab dose
      level or re-randomised from placebo to active treatment. After 24 weeks, patients
      could continue treatment with tregalizumab for 24 weeks (extension phase). The
      primary endpoint was the American College of Rheumatology 20% improvement
      criteria (ACR20) response rate at week 12. Safety and biological activity were
      monitored through week 48. RESULTS: At week 12, ACR20 response rates were not
      statistically significantly different between placebo and any of the tregalizumab
      doses. Tregalizumab injections were well tolerated; most adverse events were mild
      to moderate and comparable among treatment and placebo groups. Biological
      activity was shown by dose-dependent CD4 downmodulation. CONCLUSION: Treatment
      with tregalizumab did not show significant clinical efficacy in patients with
      active RA compared with placebo but resulted in the expected biological effect on
      CD4 modulation. Tregalizumab was generally well tolerated, and no new safety
      findings were identified. TRIAL REGISTRATION NUMBER: NCT01999192; Results.

PMID- 29343512
TI  - Response to: 'Neuropsychiatric lupus or not? Cerebral hypoperfusion by perfusion
      weighted MRI in normal-appearing white matter in primary neuropsychiatric lupus
      erythematosus' by Papadaki et al.

PMID- 29343513
TI  - Using genetic buffering relationships identified in fission yeast to reveal
      susceptibilities in cells lacking hamartin or tuberin function.
AB  - Tuberous sclerosis complex is an autosomal dominant disorder characterized by
      benign tumors arising from the abnormal activation of mTOR signaling in cells
      lacking TSC1 (hamartin) or TSC2 (tuberin) activity. To expand the genetic
      framework surrounding this group of growth regulators, we utilized the model
      eukaryote Schizosaccharomyces pombe to uncover and characterize genes that buffer
      the phenotypic effects of mutations in the orthologous tsc1 or tsc2 loci. Our
      study identified two genes: fft3 (encoding a DNA helicase) and ypa1 (encoding a
      peptidyle-prolyl cis/trans isomerase). While the deletion of fft3 or ypa1 has
      little effect in wild-type fission yeast cells, their loss in tsc1Delta or
      tsc2Delta backgrounds results in severe growth inhibition. These data suggest
      that the inhibition of Ypa1p or Fft3p might represent an 'Achilles' heel' of
      cells defective in hamartin/tuberin function. Furthermore, we demonstrate that
      the interaction between tsc1/tsc2 and ypa1 can be rescued through treatment with
      the mTOR inhibitor, torin-1, and that ypa1Delta cells are resistant to the
      glycolytic inhibitor, 2-deoxyglucose. This identifies ypa1 as a novel upstream
      regulator of mTOR and suggests that the effects of ypa1 loss, together with mTOR
      activation, combine to result in a cellular maladaptation in energy metabolism
      that is profoundly inhibitory to growth.

PMID- 29343514
TI  - TRPM2 channel-mediated regulation of autophagy maintains mitochondrial function
      and promotes gastric cancer cell survival via the JNK-signaling pathway.
AB  - A lack of effective treatment is one of the main factors contributing to gastric
      cancer-related death. Discovering effective targets and understanding their
      underlying anti-cancer mechanism are key to achieving the best response to
      treatment and to limiting side effects. Although recent studies have shown that
      the cation channel transient receptor potential melastatin-2 (TRPM2) is crucial
      for cancer cell survival, the exact mechanism remains unclear, limiting its
      therapeutic potential. Here, using molecular and functional assays, we
      investigated the role of TRPM2 in survival of gastric cancer cells. Our results
      indicated that TRPM2 knockdown in AGS and MKN-45 cells decreases cell
      proliferation and enhances apoptosis. We also observed that the TRPM2 knockdown
      impairs mitochondrial metabolism, indicated by a decrease in basal and maximal
      mitochondrial oxygen consumption rates and ATP production. These mitochondrial
      defects coincided with a decrease in autophagy and mitophagy, indicated by
      reduced levels of autophagy- and mitophagy-associated proteins (i.e. ATGs, LC3A/B
      II, and BNIP3). Moreover, we found that TRPM2 modulates autophagy through a c-Jun
      N-terminal kinase (JNK)-dependent and mechanistic target of rapamycin-independent
      pathway. We conclude that in the absence of TRPM2, down-regulation of the JNK
      signaling pathway impairs autophagy, ultimately causing the accumulation of
      damaged mitochondria and death of gastric cancer cells. Of note, by inhibiting
      cell proliferation and promoting apoptosis, the TRPM2 down-regulation enhanced
      the efficacy of paclitaxel and doxorubicin in gastric cancer cells. Collectively,
      we provide compelling evidence that TRPM2 inhibition may benefit therapeutic
      approaches for managing gastric cancer.

PMID- 29343515
TI  - Discovery of genes required for lipoteichoic acid glycosylation predicts two
      distinct mechanisms for wall teichoic acid glycosylation.
AB  - The bacterial cell wall is an important and highly complex structure that is
      essential for bacterial growth because it protects bacteria from cell lysis and
      environmental insults. A typical Gram-positive bacterial cell wall is composed of
      peptidoglycan and the secondary cell wall polymers, wall teichoic acid (WTA) and
      lipoteichoic acid (LTA). In many Gram-positive bacteria, LTA is a polyglycerol
      phosphate chain that is decorated with d-alanine and sugar residues. However, the
      function of and proteins responsible for the glycosylation of LTA are either
      unknown or not well-characterized. Here, using bioinformatics, genetic, and NMR
      spectroscopy approaches, we found that the Bacillus subtilis csbB and yfhO genes
      are essential for LTA glycosylation. Interestingly, the Listeria monocytogenes
      gene lmo1079, which encodes a YfhO homolog, was not required for LTA
      glycosylation, but instead was essential for WTA glycosylation. LTA is
      polymerized on the outside of the cell and hence can only be glycosylated
      extracellularly. Based on the similarity of the genes coding for YfhO homologs
      that are required in B. subtilis for LTA glycosylation or in L. monocytogenes for
      WTA glycosylation, we hypothesize that WTA glycosylation might also occur
      extracellularly in Listeria species. Finally, we discovered that in L.
      monocytogenes, lmo0626 (gtlB) was required for LTA glycosylation, indicating that
      the encoded protein has a function similar to that of YfhO, although the proteins
      are not homologous. Together, our results enable us to propose an updated model
      for LTA glycosylation and also indicate that glycosylation of WTA might occur
      through two different mechanisms in Gram-positive bacteria.

PMID- 29343516
TI  - Stat3-mediated alterations in lysosomal membrane protein composition.
AB  - Lysosome function is essential in cellular homeostasis. In addition to its
      recycling role, the lysosome has recently been recognized as a cellular signaling
      hub. We have shown in mammary epithelial cells, both in vivo and in vitro, that
      signal transducer and activator of transcription 3 (Stat3) modulates lysosome
      biogenesis and can promote the release of lysosomal proteases that culminates in
      cell death. To further investigate the impact of Stat3 on lysosomal function, we
      conducted a proteomic screen of changes in lysosomal membrane protein components
      induced by Stat3 using an iron nanoparticle enrichment strategy. Our results show
      that Stat3 activation not only elevates the levels of known membrane proteins but
      results in the appearance of unexpected factors, including cell surface proteins
      such as annexins and flotillins. These data suggest that Stat3 may coordinately
      regulate endocytosis, intracellular trafficking, and lysosome biogenesis to drive
      lysosome-mediated cell death in mammary epithelial cells. The methodologies
      described in this study also provide significant improvements to current
      techniques used for the purification and analysis of the lysosomal proteome.

PMID- 29343518
TI  - Fibroblast-Specific beta-Catenin Signaling Dictates the Outcome of AKI.
AB  - AKI is a devastating condition with high morbidity and mortality. The pathologic
      features of AKI are characterized by tubular injury, inflammation, and vascular
      impairment. Whether fibroblasts in the renal interstitium have a role in the
      pathogenesis of AKI is unknown. In this study, we investigated the role of
      fibroblast-specific beta-catenin signaling in dictating the outcome of AKI, using
      conditional knockout mice in which beta-catenin was specifically ablated in
      fibroblasts (Gli1-beta-cat-/-). After ischemia-reperfusion injury (IRI), Gli1
      beta-cat-/- mice had lower serum creatinine levels and less morphologic injury
      than Gli1-beta-cat+/+ littermate controls. Moreover, we detected fewer apoptotic
      cells, as well as decreased cytochrome C release; reduced expression of Bax,
      FasL, and p53; and increased phosphorylation of Akt, in the Gli1-beta-cat-/-
      kidneys. Gli1-beta-cat-/- kidneys also exhibited upregulated expression of
      proliferating cell nuclear antigen and Ki-67, which are markers of cell
      proliferation. Furthermore, Gli1-beta-cat-/- kidneys displayed suppressed NF
      kappaB signaling and cytokine expression and reduced infiltration of inflammatory
      cells. Notably, loss of beta-catenin in fibroblasts induced renal expression of
      hepatocyte growth factor (HGF) and augmented the tyrosine phosphorylation of c
      met receptor after IRI. In vitro, treatment with Wnt ligands or ectopic
      expression of active beta-catenin inhibited HGF mRNA and protein expression and
      repressed HGF promoter activity. Collectively, these results suggest that
      fibroblast-specific beta-catenin signaling can control tubular injury and repair
      in AKI by modulating HGF expression. Our studies uncover a previously
      unrecognized role for interstitial fibroblasts in the pathogenesis of AKI.

PMID- 29343519
TI  - Uremic Solute-Aryl Hydrocarbon Receptor-Tissue Factor Axis Associates with
      Thrombosis after Vascular Injury in Humans.
AB  - Individuals with CKD are particularly predisposed to thrombosis after vascular
      injury. Using mouse models, we recently described indoxyl sulfate, a tryptophan
      metabolite retained in CKD and an activator of tissue factor (TF) through aryl
      hydrocarbon receptor (AHR) signaling, as an inducer of thrombosis across the CKD
      spectrum. However, the translation of findings from animal models to humans is
      often challenging. Here, we investigated the uremic solute-AHR-TF thrombosis axis
      in two human cohorts, using a targeted metabolomics approach to probe a set of
      tryptophan products and high-throughput assays to measure AHR and TF activity.
      Analysis of baseline serum samples was performed from 473 participants with
      advanced CKD from the Dialysis Access Consortium Clopidogrel Prevention of Early
      AV Fistula Thrombosis trial. Participants with subsequent arteriovenous
      thrombosis had significantly higher levels of indoxyl sulfate and kynurenine,
      another uremic solute, and greater activity of AHR and TF, than those without
      thrombosis. Pattern recognition analysis using the components of the thrombosis
      axis facilitated clustering of the thrombotic and nonthrombotic groups. We
      further validated these findings using 377 baseline samples from participants in
      the Thrombolysis in Myocardial Infarction II trial, many of whom had CKD stage 2
      3. Mechanistic probing revealed that kynurenine enhances thrombosis after
      vascular injury in an animal model and regulates thrombosis in an AHR-dependent
      manner. This human validation of the solute-AHR-TF axis supports further studies
      probing its utility in risk stratification of patients with CKD and exploring its
      role in other diseases with heightened risk of thrombosis.

PMID- 29343521
TI  - T-type Ca2+ Channels: T for Targetable.
AB  - In the past decade, T-type Ca2+ channels (TTCC) have been unveiled as key
      regulators of cancer cell biology and thus have been proposed as chemotherapeutic
      targets. Indeed, in vitro and in vivo studies indicate that TTCC pharmacologic
      blockers have a negative impact on the viability of cancer cells and reduce tumor
      size, respectively. Consequently mibefradil, a TTCC blocker approved in 1997 as
      an antihypertensive agent but withdrawn in 1998 because of drug-drug
      interactions, was granted 10 years later the orphan drug status by the FDA to
      investigate its efficacy against brain, ovary, and pancreatic cancer. However,
      the existence of different channel isoforms with distinct physiologic roles,
      together with the lack of selective pharmacologic agents, has hindered a
      conclusive chemotherapeutic evaluation. Here, we review the available evidence on
      TTCC expression, value as prognostic markers, and effectiveness of their
      pharmacologic blockade on cancer cells in vitro and in preclinical models. We
      additionally summarize the status of clinical trials using mibefradil against
      glioblastoma multiforme. Finally, we discuss the future perspectives and the
      importance of further development of multidisciplinary research efforts on the
      consideration of TTCCs as biomarkers or targetable molecules in cancer. Cancer
      Res; 78(3); 603-9. (c)2018 AACR.

PMID- 29343520
TI  - Evidence for the ISG15-Specific Deubiquitinase USP18 as an Antineoplastic Target.
AB  - Ubiquitination and ubiquitin-like posttranslational modifications (PTM) regulate
      activity and stability of oncoproteins and tumor suppressors. This implicates
      PTMs as antineoplastic targets. One way to alter PTMs is to inhibit activity of
      deubiquitinases (DUB) that remove ubiquitin or ubiquitin-like proteins from
      substrate proteins. Roles of DUBs in carcinogenesis have been intensively
      studied, yet few inhibitors exist. Prior work provides a basis for the ubiquitin
      specific protease 18 (USP18) as an antineoplastic target. USP18 is the major DUB
      that removes IFN-stimulated gene 15 (ISG15) from conjugated proteins. Prior work
      discovered that engineered loss of USP18 increases ISGylation and in contrast to
      its gain decreases cancer growth by destabilizing growth-regulatory proteins.
      Loss of USP18 reduced cancer cell growth by triggering apoptosis. Genetic loss of
      USP18 repressed cancer formation in engineered murine lung cancer models. The
      translational relevance of USP18 was confirmed by finding its expression was
      deregulated in malignant versus normal tissues. Notably, the recent elucidation
      of the USP18 crystal structure offers a framework for developing an inhibitor to
      this DUB. This review summarizes strong evidence for USP18 as a previously
      unrecognized pharmacologic target in oncology. Cancer Res; 78(3); 587-92. (c)2018
      AACR.

PMID- 29343517
TI  - Early Infant Diet and Islet Autoimmunity in the TEDDY Study.
AB  - OBJECTIVE: To examine duration of breastfeeding and timing of complementary foods
      and risk of islet autoimmunity (IA). RESEARCH DESIGN AND METHODS: The
      Environmental Determinants of Diabetes in the Young (TEDDY) study prospectively
      follows 8,676 children with increased genetic risk of type 1 diabetes (T1D) in
      the U.S., Finland, Germany, and Sweden. This study included 7,563 children with
      at least 9 months of follow-up. Blood samples were collected every 3 months from
      birth to evaluate IA, defined as persistent, confirmed positive antibodies to
      insulin (IAAs), GAD, or insulinoma antigen-2. We examined the associations
      between diet and the risk of IA using Cox regression models adjusted for country,
      T1D family history, HLA genotype, sex, and early probiotic exposure.
      Additionally, we investigated martingale residuals and log-rank statistics to
      determine cut points for ages of dietary exposures. RESULTS: Later introduction
      of gluten was associated with increased risk of any IA and IAA. The hazard ratios
      (HRs) for every 1-month delay in gluten introduction were 1.05 (95% CI 1.01,
      1.10; P = 0.02) and 1.08 (95% CI 1.00, 1.16; P = 0.04), respectively. Martingale
      residual analysis suggested that the age at gluten introduction could be grouped
      as <4, 4-9, and >9 months. The risk of IA associated with introducing gluten
      before 4 months of age was lower (HR 0.68; 95% CI 0.47, 0.99), and the risk of IA
      associated with introducing it later than the age of 9 months was higher (HR
      1.57; 95% CI 1.07, 2.31) than introduction between 4 and 9 months of age.
      CONCLUSIONS: The timing of gluten-containing cereals and IA should be studied
      further.

PMID- 29343522
TI  - Polyol Pathway Links Glucose Metabolism to the Aggressiveness of Cancer Cells.
AB  - Cancer cells alter their metabolism to support their malignant properties. In
      this study, we report that the glucose-transforming polyol pathway (PP) gene aldo
      keto-reductase-1-member-B1 (AKR1B1) strongly correlates with epithelial-to
      mesenchymal transition (EMT). This association was confirmed in samples from lung
      cancer patients and from an EMT-driven colon cancer mouse model with p53
      deletion. In vitro, mesenchymal-like cancer cells showed increased AKR1B1 levels,
      and AKR1B1 knockdown was sufficient to revert EMT. An equivalent level of EMT
      suppression was measured by targeting the downstream enzyme sorbitol
      dehydrogenase (SORD), further pointing at the involvement of the PP. Comparative
      RNA sequencing confirmed a profound alteration of EMT in PP-deficient cells,
      revealing a strong repression of TGFbeta signature genes. Excess glucose was
      found to promote EMT through autocrine TGFbeta stimulation, while PP-deficient
      cells were refractory to glucose-induced EMT. These data show that PP represents
      a molecular link between glucose metabolism, cancer differentiation, and
      aggressiveness, and may serve as a novel therapeutic target.Significance: A
      glucose-transforming pathway in TGFbeta-driven epithelial-to-mesenchymal
      transition provides novel mechanistic insights into the metabolic control of
      cancer differentiation. Cancer Res; 78(7); 1604-18. (c)2018 AACR.

PMID- 29343523
TI  - A Novel l-Asparaginase with low l-Glutaminase Coactivity Is Highly Efficacious
      against Both T- and B-cell Acute Lymphoblastic Leukemias In Vivo.
AB  - Acute lymphoblastic leukemia (ALL) is the most common type of pediatric cancer,
      although about 4 of every 10 cases occur in adults. The enzyme drug l
      asparaginase serves as a cornerstone of ALL therapy and exploits the asparagine
      dependency of ALL cells. In addition to hydrolyzing the amino acid l-asparagine,
      all FDA-approved l-asparaginases also have significant l-glutaminase coactivity.
      Since several reports suggest that l-glutamine depletion correlates with many of
      the side effects of these drugs, enzyme variants with reduced l-glutaminase
      coactivity might be clinically beneficial if their antileukemic activity would be
      preserved. Here we show that novel low l-glutaminase variants developed on the
      backbone of the FDA-approved Erwinia chrysanthemi l-asparaginase were highly
      efficacious against both T- and B-cell ALL, while displaying reduced acute
      toxicity features. These results support the development of a new generation of
      safer l-asparaginases without l-glutaminase activity for the treatment of human
      ALL.Significance: A new l-asparaginase-based therapy is less toxic compared with
      FDA-approved high l-glutaminase enzymes Cancer Res; 78(6); 1549-60. (c)2018 AACR.

PMID- 29343524
TI  - Antitumor Properties of RAF709, a Highly Selective and Potent Inhibitor of RAF
      Kinase Dimers, in Tumors Driven by Mutant RAS or BRAF.
AB  - Resistance to the RAF inhibitor vemurafenib arises commonly in melanomas driven
      by the activated BRAF oncogene. Here, we report antitumor properties of RAF709, a
      novel ATP-competitive kinase inhibitor with high potency and selectivity against
      RAF kinases. RAF709 exhibited a mode of RAF inhibition distinct from RAF monomer
      inhibitors such as vemurafenib, showing equal activity against both RAF monomers
      and dimers. As a result, RAF709 inhibited MAPK signaling activity in tumor models
      harboring either BRAFV600 alterations or mutant N- and KRAS-driven signaling,
      with minimal paradoxical activation of wild-type RAF. In cell lines and murine
      xenograft models, RAF709 demonstrated selective antitumor activity in tumor cells
      harboring BRAF or RAS mutations compared with cells with wild-type BRAF and RAS
      genes. RAF709 demonstrated a direct pharmacokinetic/pharmacodynamic relationship
      in in vivo tumor models harboring KRAS mutation. Furthermore, RAF709 elicited
      regression of primary human tumor-derived xenograft models with BRAF, NRAS, or
      KRAS mutations with excellent tolerability. Our results support further
      development of inhibitors like RAF709, which represents a next-generation RAF
      inhibitor with unique biochemical and cellular properties that enables antitumor
      activities in RAS-mutant tumors.Significance: In an effort to develop RAF
      inhibitors with the appropriate pharmacological properties to treat RAS mutant
      tumors, RAF709, a compound with potency, selectivity, and in vivo properties, was
      developed that will allow preclinical therapeutic hypothesis testing, but also
      provide an excellent probe to further unravel the complexities of RAF kinase
      signaling. Cancer Res; 78(6); 1537-48. (c)2018 AACR.

PMID- 29343525
TI  - Lack of Remuscularization Following Transplantation of Human Embryonic Stem Cell
      Derived Cardiovascular Progenitor Cells in Infarcted Nonhuman Primates.
AB  - RATIONALE: Human pluripotent stem cell-derived cardiovascular progenitor cells
      (hPSC-CVPCs) should be thoroughly investigated in large animal studies before
      testing in clinical trials. OBJECTIVE: The main of this study is to clarify
      whether hPSC-CVPCs can engraft for long time in the heart of primates after
      myocardial infarction (MI) and compare the effectiveness and safety of
      immunosuppression with cyclosporine alone or multiple-drug regimen (MDR)
      containing cyclosporine, methylprednisolone, and basiliximab in cynomolgus
      monkeys that had received intramyocardial injections of 1*107 EGFP (enhanced
      green fluorescent protein)-expressing hPSC-CVPCs after MI. A third group of
      animals received the immunosuppression MDR but without cell therapy after MI
      (MI+MDR group). METHODS AND RESULTS: Measurements of EGFP gene levels and EGFP
      immunofluorescence staining indicated that the hPSC-CVPC engraftment rate was
      greater in the MI+MDR+CVPC group than that in the MI+cyclosporine+CVPC group.
      However, even in the MI+MDR+CVPC group, no transplanted cells could be detected
      at 140 days after transplantation. Concomitantly, immunofluorescent analysis of
      CD3, CD4, and CD8 expression indicated that T-lymphocyte infiltration in the CVPC
      transplanted hearts was less in the MDR-treated animals than in the cyclosporine
      alone-treated animals. The recovery of left ventricular function on day 28 post
      MI in the MI+MDR+CVPC group was better than that in the MI+MDR group. Apoptotic
      cardiac cells were also less common in the MI+MDR+CVPC group than in the MI+MDR
      group, although both immunosuppression regimens were associated with transient
      hepatic dysfunction. CONCLUSIONS: This is the largest study of hPSCs in nonhuman
      primates in cardiovascular field to date (n=32). Compared with cyclosporine
      alone, MDR attenuates immune rejection and improves survival of hPSC-CVPCs in
      primates; this is associated with less apoptosis of native cardiac cells and
      better recovery of left ventricular function at 28 days. However, even with MDR,
      transplanted hPSC-CVPCs do not engraft and do not survive at 140 days after
      transplantation, thereby excluding remuscularization as a mechanism for the
      functional effect.

PMID- 29343527
TI  - Visual outcomes after chemotherapy for optic pathway glioma in children with and
      without neurofibromatosis type 1: results of the International Society of
      Paediatric Oncology (SIOP) Low-Grade Glioma 2004 trial UK cohort.
AB  - AIMS: To report visual acuity (VA) outcomes following chemotherapy for optic
      pathway glioma (OPG) in children with or without neurofibromatosis type-1 (NF1)
      and to analyse associated risk factors. METHODS: A prospective, multicentre,
      cohort study involving 155 children treated between September 2004 and December
      2012. Initial and final VA was used for per-eye and per-subject analysis.
      Correlation tests were performed to determine whether initial VA predicted final
      VA. Logistic regression was used to determine whether age and tumour location
      were associated risk factors. RESULTS: 90 children had complete ophthalmological
      data. At initiation of chemotherapy, 26% and 49% of eyes with NF1-OPG and
      sporadic OPG, respectively, had VA of >=0.7 log of the minimum angle of
      resolution (logMAR). At final visit, per eye, 49% had <=0.2, 23% had 0.30-0.60
      and 28% had VA>=0.70 logMAR in the NF1-OPG group. In the sporadic OPG group, per
      eye, 32% had <=0.2, 11% had VA 0.30-0.60 and 57% had >=0.70 logMAR. Children with
      sporadic OPG, per eye, were significantly less likely to have VA outcomes <=0.60
      logMAR compared with children with NF1-OPG (OR=0.30; 95% CI 0.16 to 0.56;
      P<0.0001). Per subject, VA improved in 24%, remained stable in 35% and worsened
      in 41% of children with NF1-OPG and improved in 18%, remained stable in 43% and
      worsened in 39% of children with sporadic OPG. CONCLUSIONS: Children with and
      without NF1 demonstrated the same rate of VA improvement, stabilisation or
      worsening; however, children with sporadic OPG had a poorer VA outcome. Better
      initial VA, older age, absence of postchiasm tumour and presence of NF1 were
      associated with improved or stable VA outcomes.

PMID- 29343526
TI  - Mutations in CYB561 Causing a Novel Orthostatic Hypotension Syndrome.
AB  - RATIONALE: Orthostatic hypotension is a common clinical problem, but the
      underlying mechanisms have not been fully delineated. OBJECTIVE: We describe 2
      families, with 4 patients in total, experiencing severe life-threatening
      orthostatic hypotension because of a novel cause. METHODS AND RESULTS: As in
      dopamine beta-hydroxylase deficiency, concentrations of norepinephrine and
      epinephrine in the patients were low. Plasma dopamine beta-hydroxylase activity,
      however, was normal, and the DBH gene had no mutations. Molecular genetic
      analysis was performed to determine the underlying genetic cause. Homozygosity
      mapping and exome and Sanger sequencing revealed pathogenic homozygous mutations
      in the gene encoding cytochrome b561 (CYB561); a missense variant c.262G>A,
      p.Gly88Arg in exon 3 in the Dutch family and a nonsense mutation (c.131G>A,
      p.Trp44*) in exon 2 in the American family. Expression of CYB561 was investigated
      using RNA from different human adult and fetal tissues, transcription of RNA into
      cDNA, and real-time quantitative polymerase chain reaction. The CYB561 gene was
      found to be expressed in many human tissues, in particular the brain. The CYB561
      protein defect leads to a shortage of ascorbate inside the catecholamine
      secretory vesicles leading to a functional dopamine beta-hydroxylase deficiency.
      The concentration of the catecholamines and downstream metabolites was measured
      in brain and adrenal tissue of 6 CYB561 knockout mice (reporter-tagged deletion
      allele [post-Cre], genetic background C57BL/6NTac). The concentration of
      norepinephrine and normetanephrine was decreased in whole-brain homogenates of
      the CYB561(-/-) mice compared with wild-type mice (P<0.01), and the concentration
      of normetanephrine and metanephrine was decreased in adrenal glands (P<0.01),
      recapitulating the clinical phenotype. The patients responded favorably to
      treatment with l-dihydroxyphenylserine, which can be converted directly to
      norepinephrine. CONCLUSIONS: This study is the first to implicate cytochrome b561
      in disease by showing that pathogenic mutations in CYB561 cause an as yet unknown
      disease in neurotransmitter metabolism causing orthostatic hypotension.

PMID- 29343528
TI  - Effect of intravitreal triamcinolone acetonide injection at the end of vitrectomy
      for vitreous haemorrhage related to proliferative diabetic retinopathy.
AB  - BACKGROUND/AIMS: To investigate whether intravitreal injection of triamcinolone
      acetonide (IVTA) combined with vitrectomy prevents postoperative inflammation in
      patients with vitreous haemorrhage (VH) due to proliferative diabetic retinopathy
      (PDR). METHODS: This prospective, multicentre, randomised study conducted at
      seven sites in Japan enrolled patients diagnosed as having VH following PDR.
      Patients underwent vitrectomy with (IVTA+VIT group) or without (VIT group) IVTA
      at the end of the surgery. Anterior flare intensity (AFI), central retinal
      thickness (CRT), best-corrected visual acuity (BCVA) and intraocular pressure
      (IOP) were measured before and at 3 days, 1 week, 1, 3 and 6 months after surgery
      and compared. RESULTS: Number of patients who completed 6 months of follow-up was
      40 and 41 in VIT group and IVTA+VIT group, respectively. AFI was significantly
      higher in the VIT group than in the IVTA+VIT group at 3 days (P=0.033), 1 week
      (P=0.019) and 1 month (P=0.037). There were no significant differences in CRT,
      BCVA and IOP between the groups through the observational periods. In the cases
      with macular oedema >350 um of CRT at 3 days, CRT was significantly lower in the
      IVTA+VIT group than in the VIT group at 1 month (P=0.041). CONCLUSIONS: IVTA
      combined with vitrectomy and cataract surgery contributed to inhibit the
      postoperative inflammation in patients with VH due to PDR. The effect of IVTA in
      the reduction of diabetic macular oedema may be limited to the early stage after
      surgery. TRIAL REGISTRATION NUMBER: UMIN000020376, Post-results.

PMID- 29343529
TI  - Quarter-Descemet membrane endothelial keratoplasty (Quarter-DMEK) for Fuchs
      endothelial corneal dystrophy: 6 months clinical outcome.
AB  - BACKGROUND/AIM: To assess the clinical outcome of the first series of Quarter
      Descemet membrane endothelial keratoplasty (Quarter-DMEK), a potential hybrid
      technique between 'descemetorhexis only' and conventional, circular DMEK.
      METHODS: Prospective interventional case series at a tertiary referral centre.
      Twelve eyes of 12 patients with central Fuchs endothelial corneal dystrophy
      underwent Quarter-DMEK, that is, transplantation of one quadrant of a full
      diameter DMEK graft, and were evaluated for best-corrected visual acuity (BCVA),
      endothelial cell density (ECD) and complications up to 6 months postoperatively.
      RESULTS: At 6 months postoperatively, all eyes reached a BCVA of >=20/40 (>=0.5),
      11/12 (92%) of >=20/25 (>=0.8) and 6/12 (50%) of >=20/20 (>=1.0). Mean central
      ECD decreased from 2867 (+/-161) cells/mm2 before to 1255 (+/-514) cells/mm2 at 1
      month, 1058 (+/-455) cells/mm2 at 3 months and 968 (+/-427) cells/mm2 at 6 months
      after surgery. Rebubbling was performed in 4/12 eyes (33%) within the first two
      months. CONCLUSIONS: Quarter-DMEK may be a feasible procedure that allows for
      visual outcomes similar to conventional, circular DMEK. The relatively large drop
      in ECD within the first month may have resulted from more extensive endothelial
      cell migration and/or measurement error (at the graft edges). If longer-term
      outcomes would resemble those of conventional DMEK, Quarter-DMEK may potentially
      quadruple the availability of endothelial grafts.

PMID- 29343530
TI  - Peripapillary vascular changes in radiation optic neuropathy: an optical
      coherence tomography angiography grading.
AB  - AIMS: To investigate peripapillary vascular changes secondary to radiation optic
      neuropathy (RON) using optical coherence tomography angiography (OCT-A) and to
      propose a clinical grading of RON based on OCT-A findings. METHODS: Thirty-four
      patients affected by RON were consecutively included. Each patient underwent best
      corrected visual acuity measurement (ETDRS score) and OCT-A (Nidek RS-3000
      Advance device, Nidek, Gamagori, Japan). The radial peripapillary capillary
      plexus (RPCP) and the entire peripapillary capillary bed (EPCB) were analysed.
      Quantitative analysis of the OCT-A images was performed using open-source
      available ImageJ software (National Institutes of Health, Bethesda, Maryland,
      USA). Qualitative analysis based on the proposed clinical grading (Grades 0-4)
      was also performed by two masked graders. RESULTS: RON clinical (qualitative)
      classification based on RPCP correlated with the quantitative RPCP perfusion
      analysis (P=0.0001). RON clinical classification based on RPCP statistically
      correlated with ETDRS score (P=0.001). RON clinical classification based on EPCB
      also correlated with the quantitative EPCB perfusion analysis and ETDRS score
      (P=0.02 and P=0.01, respectively). Compared with the clinical classification
      based on EPCB, the qualitative classification based on RPCP reached a higher
      intergrader agreement (0.96 and 0.86, respectively). CONCLUSION: OCT-A can be
      used to detect RPCP abnormalities and to clinically classify RON with a high
      interexaminer agreement. The proposed clinical classification is supported by the
      quantitative analysis based on the use of specific images elaboration techniques
      and correlates with visual acuity of the examined eyes.

PMID- 29343531
TI  - Comparison of immunoblotting (IgA and IgG) and the Goldmann-Witmer coefficient
      for diagnosis of ocular toxoplasmosis in immunocompetent patients.
AB  - BACKGROUND: Ocular toxoplasmosis (OT) is a common cause of posterior uveitis
      worldwide. The diagnosis of OT is based on clinical findings, but in most cases,
      laboratory tests are required to confirm the aetiology, especially when other
      diseases are suspected. The aim of this study was to evaluate which methods,
      between the Goldmann-Witmer coefficient (GWC) and immunoblotting (IB) with both
      IgG and IgA, in aqueous humour (AH) samples, can be the most sensitive to
      diagnose OT, in current practice, especially in the first three weeks. METHODS:
      Retrospectively reviewed records of 87 consecutive patients who had underwent AH
      and serum sample, 42 patients with suspected OT and 45 patients with suspected
      other ocular inflammatory diseases. All samples were analysed by both GWC and IB.
      RESULTS: The GWC was significant in 47.6% of patients presenting with suspected
      OT. The intraocular production of specific antibody anti-Toxoplasma gondii IgG
      and IgA was revealed by IB in 71.4% of samples. The combination of these two
      methods increased the sensitivity to 76.2%. Based on the interval between symptom
      onset and paracentesis, IB had a greater sensitivity than GWC when sample of AH
      was taken in the first three weeks (64.7% vs 23.5%, P=0.039), while the
      difference between the sensitivity of IB and GWC was less important in cases with
      an interval >3 weeks (76% vs 64% P=0.625). CONCLUSION: IB seems to be more useful
      than the GWC if only one of these methods can be performed, especially during the
      first three weeks after symptom onset.

PMID- 29343532
TI  - Clinical Laboratory Practice Recommendations for the Use of Cardiac Troponin in
      Acute Coronary Syndrome: Expert Opinion from the Academy of the American
      Association for Clinical Chemistry and the Task Force on Clinical Applications of
      Cardiac Bio-Markers of the International Federation of Clinical Chemistry and
      Laboratory Medicine.
AB  - This document is an essential companion to the third iteration of the National
      Academy of Clinical Biochemistry [NACB,8 now the American Association for
      Clinical Chemistry (AACC) Academy] Laboratory Medicine Practice Guidelines (LMPG)
      on cardiac markers. The expert consensus recommendations were drafted in
      collaboration with the International Federation of Clinical Chemistry and
      Laboratory Medicine Task Force on Clinical Applications of Bio-Markers (IFCC TF
      CB). We determined that there is sufficient clinical guidance on the use of
      cardiac troponin (cTn) testing from clinical practice groups. Thus, in this
      expert consensus document, we focused on clinical laboratory practice
      recommendations for high-sensitivity (hs)-cTn assays. This document utilized the
      expert opinion class of evidence to focus on the following 10 topics: (a) quality
      control (QC) utilization, (b) validation of the lower reportable analytical
      limits, (c) units to be used in reporting measurable concentrations for patients
      and QC materials, (d) 99th percentile sex-specific upper reference limits to
      define the reference interval; (e) criteria required to define hs-cTn assays, (f)
      communication with clinicians and the laboratory's role in educating clinicians
      regarding the influence of preanalytic and analytic problems that can confound
      assay results, (g) studies on hs-cTn assays and how authors need to document
      preanalytical and analytical variables, (h) harmonizing and standardizing assay
      results and the role of commutable materials, (i) time to reporting of results
      from sample receipt and sample collection, and (j) changes in hs-cTn
      concentrations over time and the role of both analytical and biological
      variabilities in interpreting results of serial blood collections.

PMID- 29343533
TI  - How Clinical Laboratories May Improve Their Performance: The "High-Sensitivity"
      Troponin Paradigm.

PMID- 29343534
TI  - Effect of Acute Coronary Syndrome Probability on Diagnostic and Prognostic
      Performance of High-Sensitivity Cardiac Troponin.
AB  - BACKGROUND: There is concern that high-sensitivity cardiac troponin (hs-cTn) may
      have low diagnostic accuracy in patients with low acute coronary syndrome (ACS)
      probability. METHODS: We prospectively stratified patients presenting with acute
      chest discomfort to the emergency department (ED) into 3 groups according to
      their probability for ACS as assessed by the treating ED physician using a visual
      analog scale: <=10%, 11% to 79%, and >=80%, reviewing all information available
      at 90 min. hs-cTnT and hs-cTnI concentrations were determined in a blinded
      fashion. Two independent cardiologists adjudicated the final diagnosis. RESULTS:
      Among 3828 patients eligible for analysis, 1189 patients had low (<=10%)
      probability for ACS. The incidence of non-ST-segment elevation myocardial
      infarction (NSTEMI) increased from 1.3% to 12.2% and 54.8% in patients with low,
      intermediate, and high ACS probability, respectively. The positive predictive
      value of hs-cTnT and hs-cTnI was low in patients with low ACS probability and
      increased with the incidence of NSTEMI, whereas the diagnostic accuracy of hs
      cTnT and hs-cTnI for NSTEMI as quantified by the area under the curve (AUC) was
      very high and comparable among all 3 strata, e.g., AUC hs-cTnI, 0.96 (95% CI,
      0.94-0.97); 0.87 (95% CI, 0.85-0.89); and 0.89 (95% CI, 0.87-0.92), respectively.
      Findings were validated using bootstrap analysis as an alternative methodology to
      define ACS probability. Similarly, higher hs-cTnT/I concentrations independently
      predicted all-cause mortality within 2 years (e.g., hs-cTnT hazard ratio, 1.39;
      95% CI, 1.27-1.52), irrespective of ACS probability. CONCLUSIONS: Diagnostic and
      prognostic accuracy and utility of hs-cTnT and hs-cTnI remain high in patients
      with acute chest discomfort and low ACS probability.ClinicalTrials.gov
      Identifier: NCT00470587.

PMID- 29343535
TI  - Debates in Pain Management Testing.

PMID- 29343536
TI  - Current and Emerging Multianalyte Assays with Algorithmic Analyses-Are
      Laboratories Ready for Clinical Adoption?

PMID- 29343537
TI  - A search for ceramide binding proteins using bifunctional lipid analogs yields
      CERT-related protein StarD7.
AB  - Ceramides are central intermediates of sphingolipid metabolism with dual roles as
      mediators of cellular stress signaling and mitochondrial apoptosis. How ceramides
      exert their cytotoxic effects is unclear and their poor solubility in water
      hampers a search for specific protein interaction partners. Here, we report the
      application of a photoactivatable and clickable ceramide analog, pacCer, to
      identify ceramide binding proteins and unravel the structural basis by which
      these proteins recognize ceramide. Besides capturing ceramide transfer protein
      (CERT) from a complex proteome, our approach yielded CERT-related steroidogenic
      acute regulatory protein D7 (StarD7) as novel ceramide binding protein. Previous
      work revealed that StarD7 is required for efficient mitochondrial import of
      phosphatidylcholine (PC) and serves a critical role in mitochondrial function and
      morphology. Combining site-directed mutagenesis and photoaffinity labeling
      experiments, we demonstrate that the steroidogenic acute regulatory transfer
      domain of StarD7 harbors a common binding site for PC and ceramide. While StarD7
      lacks robust ceramide transfer activity in vitro, we find that its ability to
      shuttle PC between model membranes is specifically affected by ceramides. Besides
      demonstrating the suitability of pacCer as a tool to hunt for ceramide binding
      proteins, our data point at StarD7 as a candidate effector protein by which
      ceramides may exert part of their mitochondria-mediated cytotoxic effects.

PMID- 29343538
TI  - Impact of dietary omega3 polyunsaturated fatty acid supplementation on brown and
      brite adipocyte function.
AB  - The recent characterization of functional brown adipose tissue in adult humans
      has opened new perspectives for regulation of energy expenditure with respect to
      obesity and diabetes. Furthermore, dietary recommendations have taken into
      account the insufficient dietary intake of omega3 PUFAs and the concomitant
      excessive intake of omega6 PUFA associated with the occurrence of
      overweight/obesity. We aimed to study whether omega3 PUFAs could play a role in
      the recruitment and function of energy-dissipating brown/brite adipocytes. We
      show that omega3 PUFA supplementation has a beneficial effect on the thermogenic
      function of adipocytes. In vivo, a low dietary omega6:omega3 ratio improved the
      thermogenic response of brown and white adipose tissues to beta3-adrenergic
      stimulation. This effect was recapitulated in vitro by PUFA treatment of hMADS
      adipocytes. We pinpointed the omega6-derived eicosanoid prostaglandin (PG)F2alpha
      as the molecular origin because the effects were mimicked with a specific
      PGF2alpha receptor agonist. PGF2alpha level in hMADS adipocytes was reduced in
      response to omega3 PUFA supplementation. The recruitment of thermogenic
      adipocytes is influenced by the local quantity of individual oxylipins, which is
      controlled by the omega6:omega3 ratio of available lipids. In human nutrition,
      energy homeostasis may thus benefit from the implementation of a more balanced
      dietary omega6:omega3 ratio.

PMID- 29343539
TI  - Buruli Ulcer: Review of a Neglected Skin Mycobacterial Disease.
AB  - Buruli ulcer is caused by Mycobacterium ulcerans This neglected disease occurs in
      scattered foci around the world, with a higher concentration of cases in West
      Africa. The mycobacteria produce mycolactones that cause tissue necrosis. The
      disease presents as a painless skin nodule that ulcerates as necrosis expands.
      Finding acid-fast bacilli in smears or histopathology, culturing the
      mycobacteria, and performing M. ulcerans PCR in presumptive cases confirm the
      diagnosis. Medical treatment with oral rifampin and intramuscular streptomycin or
      oral treatment with rifampin plus clarithromycin for 8 weeks is supported by the
      World Health Organization. This review summarizes the epidemiology, pathogenesis,
      clinical presentation, diagnostic tests, and advances in treatment.

PMID- 29343540
TI  - Point-Counterpoint: Meningitis/Encephalitis Syndromic Testing in the Clinical
      Laboratory.
AB  - INTRODUCTIONSyndromic panels were first FDA cleared for detection of respiratory
      pathogens in 2008. Since then, other panels have been approved by the FDA, and
      most recently, the FilmArray meningitis/encephalitis panel (BioFire, Salt Lake
      City, UT) has become available. This assay detects 14 targets within 1 h and
      includes pathogens that typically cause different manifestations of infection,
      although they infect the same organ system. Several studies have reported both
      false-positive and false-negative results with this test, and all agree that the
      cost is significant. As with other panels, health care systems have adopted
      different strategies for offering this assay. Some have implemented strategies to
      limit the use of the test to certain patient populations, others have elected not
      to offer the test, and others have elected not to offer the test and instead
      request that providers order specific PCRs for the pathogens that best fit the
      patient's symptoms. In this Point-Counterpoint, Jennifer Dien Bard of the
      Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles,
      and of the Keck School of Medicine at the University of Southern California
      explains why laboratories should offer these assays without restriction. Kevin
      Alby of the University of Pennsylvania explains the concerns about the use of
      these assays as first-line tests and why some limitations on their use might be
      appropriate.

PMID- 29343541
TI  - Immune Monitoring of Infectious Complications in Transplant Patients: an
      Important Step towards Improved Clinical Management.
AB  - Immune reconstitution following organ transplantation is absolutely critical in
      preventing infectious complications. However, understanding the kinetics of
      immune reconstitution and its potential impact on the clinical management of
      transplant patients remains a significant challenge. Over the last decade,
      various platform technologies have emerged which have provided important insights
      into the immune reconstitution kinetics in transplant patients. However, many of
      these technologies are too complicated and cumbersome to implement in a clinical
      setting. In this issue of the Journal of Clinical Microbiology, Chiereghin et al.
      (J. Clin. Microbiol. 56:e01040-17, 2018, https://doi.org/10.1128/JCM.01040-17)
      report the results of their evaluation of the QuantiFERON-CMV (QFN-CMV) assay to
      assess human cytomegalovirus (CMV)-specific CD8+ T-cell immunity in heart
      transplant recipients as a prognostic tool. These studies showed that patients
      with absence of global immune reactivity in the QFN-CMV assay were at a higher
      risk of developing CMV after discontinuing antiviral prophylaxis. Furthermore,
      failure to reconstitute CMV-specific immunity after resolution of the first
      episode of viremia was associated with viral relapse. These observations, along
      with other recent clinical studies utilizing the QFN-CMV assay, demonstrate that
      systematic monitoring of antiviral immunity can be successfully used as a
      prognostic tool and also to guide changes to the clinical management of
      transplant patients.

PMID- 29343542
TI  - Clinical Validation of SensiTest Colistin, a Broth Microdilution-Based Method To
      Evaluate Colistin MICs.
AB  - The global spread of multidrug-resistant Gram-negative bacteria has led to the
      return of colistin for treating severe infections. Recently, different plasmid
      mediated genes conferring resistance to this drug were described and reported
      worldwide. International committees (EUCAST/CLSI) reevaluated inconsistencies
      surrounding colistin antimicrobial susceptibility testing (AST), concluding that
      broth microdilution (BMD) should serve as the reference method for AST. The
      development of an accurate, reproducible commercial test based on BMD is
      therefore highly desirable. SensiTest Colistin (STC), a BMD-based compact 4-test
      panel containing the lyophilized antibiotic in 7 2-fold dilutions (0.25 to 16
      MUg/ml) was here compared with the EUCAST-CLSI standard reference method (BMD)
      and, for some isolates, with the automated Phoenix 100 system (PHX). A total of
      353 bacterial strains were evaluated by two different laboratories; 137 isolates
      were resistant to colistin (19 were intrinsically resistant, 83 harbored the mcr
      1 gene). Essential agreement (EA) between STC and BMD was obtained for 339 out of
      the 353 strains tested (96.0%). Overall categorical agreement was obtained for
      349 out of the 353 strains analyzed (98.9%). Two major errors (MEs; 0.93%) and
      two very major errors (VMEs; 1.46%) were documented. STC appeared to be a simple
      but highly reliable test with good reproducibility even with panels stored at
      room temperature or at 35 degrees C. Moreover, STC showed a good performance with
      strains carrying the mcr-1 gene, with a 98.8% EA. As the secondary endpoint of
      our study, VMEs for PHX were documented for 6 isolates (10%).

PMID- 29343543
TI  - An Autoimmune Disease-Associated Risk Variant in the TNFAIP3 Gene Plays a
      Protective Role in Brucellosis That Is Mediated by the NF-kappaB Signaling
      Pathway.
AB  - Naturally occurring functional variants (rs148314165 and rs200820567,
      collectively referred to as TT>A) reduce the expression of the tumor necrosis
      factor alpha-induced protein 3 (TNFAIP3) gene, a negative regulator of NF-kappaB
      signaling, and predispose individuals to autoimmune disease. In this analysis, we
      conducted a genetic association study of the TT>A variants in 1,209 controls and
      150 patients with brucellosis, an infectious disease, and further assessed the
      role of the variants in brucellosis. Our data demonstrated that the TT>A variants
      were correlated with cases of brucellosis (P = 0.002; odds ratio [OR] = 0.34) and
      with individuals who had a positive serum agglutination test (SAT) result (titer
      of >1/160) (P = 4.2 * 10-6; OR = 0.23). A functional study demonstrated that
      brucellosis patients carrying the protective allele (A) showed significantly
      lower expression levels of the TNFAIP3 gene in their peripheral blood mononuclear
      cells and showed increased NF-kappaB signaling. Monocytes from individuals
      carrying the A allele that were stimulated with Brucella abortus had lower mRNA
      levels of TNFAIP3 and produced more interleukin-10 (IL-10), IL-6, and IL-1beta
      than those from TT allele carriers. These data showed that autoimmune disease
      associated risk variants, TT>A, of the TNFAIP3 locus play a protective role in
      the pathogenesis of brucellosis. Our findings suggest that a disruption of the
      normal function of the TNFAIP3 gene might serve as a therapeutic target for the
      treatment of brucellosis.

PMID- 29343544
TI  - How to navigate counter dogmatic research findings.

PMID- 29343545
TI  - Tolloid cleavage activates latent GDF8 by priming the pro-complex for
      dissociation.
AB  - Growth differentiation factor 8 (GDF8)/myostatin is a latent TGF-beta family
      member that potently inhibits skeletal muscle growth. Here, we compared the
      conformation and dynamics of precursor, latent, and Tolloid-cleaved GDF8 pro
      complexes to understand structural mechanisms underlying latency and activation
      of GDF8. Negative stain electron microscopy (EM) of precursor and latent pro
      complexes reveals a V-shaped conformation that is unaltered by furin cleavage and
      sharply contrasts with the ring-like, cross-armed conformation of latent TGF
      beta1. Surprisingly, Tolloid-cleaved GDF8 does not immediately dissociate, but in
      EM exhibits structural heterogeneity consistent with partial dissociation.
      Hydrogen-deuterium exchange was not affected by furin cleavage. In contrast,
      Tolloid cleavage, in the absence of prodomain-growth factor dissociation,
      increased exchange in regions that correspond in pro-TGF-beta1 to the alpha1
      helix, latency lasso, and beta1-strand in the prodomain and to the beta6'- and
      beta7'-strands in the growth factor. Thus, these regions are important in
      maintaining GDF8 latency. Our results show that Tolloid cleavage activates latent
      GDF8 by destabilizing specific prodomain-growth factor interfaces and primes the
      growth factor for release from the prodomain.

PMID- 29343546
TI  - p62 filaments capture and present ubiquitinated cargos for autophagy.
AB  - The removal of misfolded, ubiquitinated proteins is an essential part of the
      protein quality control. The ubiquitin-proteasome system (UPS) and autophagy are
      two interconnected pathways that mediate the degradation of such proteins. During
      autophagy, ubiquitinated proteins are clustered in a p62-dependent manner and are
      subsequently engulfed by autophagosomes. However, the nature of the protein
      substrates targeted for autophagy is unclear. Here, we developed a reconstituted
      system using purified components and show that p62 and ubiquitinated proteins
      spontaneously coalesce into larger clusters. Efficient cluster formation requires
      substrates modified with at least two ubiquitin chains longer than three moieties
      and is based on p62 filaments cross-linked by the substrates. The reaction is
      inhibited by free ubiquitin, K48-, and K63-linked ubiquitin chains, as well as by
      the autophagosomal marker LC3B, suggesting a tight cross talk with general
      proteostasis and autophagosome formation. Our study provides mechanistic insights
      on how substrates are channeled into autophagy.

PMID- 29343547
TI  - Molecular Pathways for Immune Recognition of Preproinsulin Signal Peptide in Type
      1 Diabetes.
AB  - The signal peptide region of preproinsulin (PPI) contains epitopes targeted by
      HLA-A-restricted (HLA-A0201, A2402) cytotoxic T cells as part of the pathogenesis
      of beta-cell destruction in type 1 diabetes. We extended the discovery of the PPI
      epitope to disease-associated HLA-B*1801 and HLA-B*3906 (risk) and HLA-A*1101 and
      HLA-B*3801 (protective) alleles, revealing that four of six alleles present
      epitopes derived from the signal peptide region. During cotranslational
      translocation of PPI, its signal peptide is cleaved and retained within the
      endoplasmic reticulum (ER) membrane, implying it is processed for immune
      recognition outside of the canonical proteasome-directed pathway. Using in vitro
      translocation assays with specific inhibitors and gene knockout in PPI-expressing
      target cells, we show that PPI signal peptide antigen processing requires signal
      peptide peptidase (SPP). The intramembrane protease SPP generates cytoplasm
      proximal epitopes, which are transporter associated with antigen processing
      (TAP), ER-luminal epitopes, which are TAP independent, each presented by
      different HLA class I molecules and N-terminal trimmed by ER aminopeptidase 1 for
      optimal presentation. In vivo, TAP expression is significantly upregulated and
      correlated with HLA class I hyperexpression in insulin-containing islets of
      patients with type 1 diabetes. Thus, PPI signal peptide epitopes are processed by
      SPP and loaded for HLA-guided immune recognition via pathways that are enhanced
      during disease pathogenesis.

PMID- 29343548
TI  - Loss of B-Cell Anergy in Type 1 Diabetes Is Associated With High-Risk HLA and Non
      HLA Disease Susceptibility Alleles.
AB  - Although B cells reactive with islet autoantigens are silenced by tolerance
      mechanisms in healthy individuals, they can become activated and contribute to
      the development of type 1 diabetes. We previously demonstrated that high-affinity
      insulin-binding B cells (IBCs) occur exclusively in the anergic (BND) compartment
      in peripheral blood of healthy subjects. Consistent with their activation early
      in disease development, high-affinity IBCs are absent from the BND compartment of
      some first-degree relatives (FDRs) as well as all patients with autoantibody
      positive prediabetes and new-onset type 1 diabetes, a time when they are found in
      pancreatic islets. Loss of BND IBCs is associated with a loss of the entire BND B
      cell compartment consistent with provocation by an environmental trigger or
      predisposing genetic factors. To investigate potential mechanisms operative in
      subversion of B-cell tolerance, we explored associations between HLA and non-HLA
      type 1 diabetes-associated risk allele genotypes and loss of BNDs in FDRs. We
      found that high-risk HLA alleles and a subset of non-HLA risk alleles (i.e.,
      PTPN2 [rs1893217], INS [rs689], and IKZF3 [rs2872507]), relevant to B- and T-cell
      development and function are associated with loss of anergy. Hence, the results
      suggest a role for risk-conferring alleles in perturbation of B-cell anergy
      during development of type 1 diabetes.

PMID- 29343549
TI  - Intracellular vesicle trafficking plays an essential role in mitochondrial
      quality control.
AB  - The Drosophila gene products Bet1, Slh and CG10144, predicted to function in
      intracellular vesicle trafficking, were previously found to be essential for
      mitochondrial nucleoid maintenance. Here we show that Slh and Bet1 co-operate to
      maintain mitochondrial functions. In their absence, mitochondrial content,
      membrane potential and respiration became abnormal, accompanied by mitochondrial
      proteotoxic stress, but without direct effects on mtDNA. Immunocytochemistry
      showed that both Slh and Bet1 are localized at the Golgi, together with a
      proportion of Rab5-positive vesicles. Some Bet1, as well as a tiny amount of Slh,
      co-fractionated with highly purified mitochondria, whilst live-cell imaging
      showed coincidence of fluorescently tagged Bet1 with most Lysotracker-positive
      and a small proportion of Mitotracker-positive structures. This 3-way association
      was disrupted in cells knocked down for Slh, although co-localized lysosomal and
      mitochondrial signals were still seen. Neither Slh nor Bet1 were required for
      global mitophagy or endocytosis, but prolonged Slh knockdown resulted in G2
      growth arrest, with increased cell diameter. These effects were shared with
      knockdown of betaCOP but not of CG1044, Snap24 or Syntaxin6. Our findings
      implicate vesicle sorting at the cis-Golgi in mitochondrial quality control.

PMID- 29343550
TI  - Cdk1-dependent phosphoinhibition of a formin-F-BAR interaction opposes
      cytokinetic contractile ring formation.
AB  - In Schizosaccharomyces pombe, cytokinesis requires the assembly and constriction
      of an actomyosin-based contractile ring (CR). A single essential formin, Cdc12,
      localizes to the cell middle upon mitotic onset and nucleates the F-actin of the
      CR. Cdc12 medial recruitment is mediated in part by its direct binding to the F
      BAR scaffold Cdc15. Given that Cdc12 is hyperphosphorylated in M phase, we
      explored whether Cdc12 phosphoregulation impacts its association with Cdc15
      during mitosis. We found that Cdk1, a major mitotic kinase, phosphorylates Cdc12
      on six N-terminal residues near the Cdc15-binding site, and phosphorylation on
      these sites inhibits its interaction with the Cdc15 F-BAR domain. Consistent with
      this finding, a cdc12 mutant with all six Cdk1 sites changed to phosphomimetic
      residues (cdc12-6D) displays phenotypes similar to cdc12-P31A, in which the Cdc15
      binding motif is disrupted; both show reduced Cdc12 at the CR and delayed CR
      formation. Together, these results indicate that Cdk1 phosphorylation of formin
      Cdc12 antagonizes its interaction with Cdc15 and thereby opposes Cdc12's CR
      localization. These results are consistent with a general role for Cdk1 in
      inhibiting cytokinesis until chromosome segregation is complete.

PMID- 29343551
TI  - Two subunits of the exocyst, Sec3p and Exo70p, can function exclusively on the
      plasma membrane.
AB  - The exocyst is an octameric complex that tethers secretory vesicles to the plasma
      membrane in preparation for fusion. We anchored each subunit with a transmembrane
      (TM) domain at its N- or C-terminus. Only N-terminally anchored TM-Sec3p and C
      terminally anchored Exo70p-TM proved functional. These findings orient the
      complex with respect to the membrane and establish that Sec3p and Exo70p can
      function exclusively on the membrane. The functions of TM-Sec3p and Exo70p-TM
      were largely unaffected by blocks in endocytic recycling, suggesting that they
      act on the plasma membrane rather than on secretory vesicles. Cytosolic pools of
      the other exocyst subunits were unaffected in TM-sec3 cells, while they were
      partially depleted in exo70-TM cells. Blocking actin-dependent delivery of
      secretory vesicles in act1-3 cells results in loss of Sec3p from the purified
      complex. Our results are consistent with a model in which Sec3p and Exo70p can
      function exclusively on the plasma membrane while the other subunits are brought
      to them on secretory vesicles.

PMID- 29343552
TI  - Constitutive centromere-associated network contacts confer differential stability
      on CENP-A nucleosomes in vitro and in the cell.
AB  - Eukaryotic centromeres are defined by the presence of nucleosomes containing the
      histone H3 variant, centromere protein A (CENP-A). Once incorporated at
      centromeres, CENP-A nucleosomes are remarkably stable, exhibiting no detectable
      loss or exchange over many cell cycles. It is currently unclear whether this
      stability is an intrinsic property of CENP-A containing chromatin or whether it
      arises from proteins that specifically associate with CENP-A chromatin. Two
      proteins, CENP-C and CENP-N, are known to bind CENP-A human nucleosomes directly.
      Here we test the hypothesis that CENP-C or CENP-N stabilize CENP-A nucleosomes in
      vitro and in living cells. We show that CENP-N stabilizes CENP-A nucleosomes
      alone and additively with CENP-C in vitro. However, removal of CENP-C and CENP-N
      from cells, or mutating CENP-A so that it no longer interacts with CENP-C or CENP
      N, had no effect on centromeric CENP-A stability in vivo. Thus, the stability of
      CENP-A nucleosomes in chromatin does not arise solely from its interactions with
      CENP-C or CENP-N.

PMID- 29343553
TI  - Molecular Mechanisms of Biased and Probe-Dependent Signaling at CXC-Motif
      Chemokine Receptor CXCR3 Induced by Negative Allosteric Modulators.
AB  - Our recent explorations of allosteric modulators with improved properties
      resulted in the identification of two biased negative allosteric modulators,
      BD103 (N-1-{[3-(4-ethoxyphenyl)-4-oxo-3,4-dihydropyrido[2,3-d]pyrimi
      din2yl]ethyl}-4-(4-fluorobutoxy)-N-[(1-methylpiperidin-4-yl)methyl}]butanamide)
      and BD064 (5-[(N-{1-[3-(4-ethoxyphenyl)-4-oxo-3,4-dihydropyrido[2,3-d]pyrimidin-2
      yl]ethyl-2-[4-fluoro-3-(trifluoromethyl)phenyl]acetamido)methyl]-2
      fluorophenyl}boronic acid), that exhibited probe-dependent inhibition of CXC
      motif chemokine receptor CXCR3 signaling. With the intention to elucidate the
      structural mechanisms underlying their selectivity and probe dependence, we used
      site-directed mutagenesis combined with homology modeling and docking to identify
      amino acids of CXCR3 that contribute to modulator binding, signaling, and
      transmission of cooperativity. With the use of allosteric radioligand RAMX3
      ([3H]N-{1-[3-(4-ethoxyphenyl)-4-oxo-3,4-dihydropyrido[2,3-d]pyrimidin-2-yl]ethyl}
      2-[4-fluoro-3-(trifluoromethyl)phenyl]-N-[(1-methylpiperidin-4
      yl)methyl]acetamide), we identified that F1313.32 and Y3087.43 contribute
      specifically to the binding pocket of BD064, whereas D1864.60 solely participates
      in the stabilization of binding conformation of BD103. The influence of mutations
      on the ability of negative allosteric modulators to inhibit chemokine-mediated
      activation (CXCL11 and CXCL10) was assessed with the bioluminescence resonance
      energy transfer-based cAMP and beta-arrestin recruitment assay. Obtained data
      revealed complex molecular mechanisms governing biased and probe-dependent
      signaling at CXCR3. In particular, F1313.32, S3047.39, and Y3087.43 emerged as
      key residues for the compounds to modulate the chemokine response. Notably,
      D1864.60, W2686.48, and S3047.39 turned out to play a role in signal pathway
      selectivity of CXCL10, as mutations of these residues led to a G protein-active
      but beta-arrestin-inactive conformation. These diverse effects of mutations
      suggest the existence of ligand- and pathway-specific receptor conformations and
      give new insights in the sophisticated signaling machinery between allosteric
      ligands, chemokines, and their receptors, which can provide a powerful platform
      for the development of new allosteric drugs with improved pharmacological
      properties.

PMID- 29343555
TI  - Antagonism of Integrin CD11b Affords Protection against Endotoxin Shock and
      Polymicrobial Sepsis via Attenuation of HMGB1 Nucleocytoplasmic Translocation and
      Extracellular Release.
AB  - High mobility group box 1 (HMGB1), a chromatin-binding nuclear protein, plays a
      critical role in sepsis by acting as a key "late-phase" inflammatory mediator.
      Integrin CD11b is essential for inflammatory cell activation and migration, thus
      mediating inflammatory responses. However, it is unclear whether CD11b
      participates in the development of sepsis. In this study, we report that CD11b
      contributes to LPS-induced endotoxin shock and microbial sepsis, as antagonism of
      CD11b with the CD11b blocking Ab or CD11b inhibitor Gu-4 protects mice against
      LPS- and microbial sepsis-related lethality, which is associated with
      significantly diminished serum HMGB1 levels. Consistent with this, CD11b
      deficient mice were more resistant to microbial sepsis with a much lower serum
      HMGB1 level compared with wild-type mice. Pharmacological blockage and genetic
      knockdown/knockout of CD11b in murine macrophages hampered LPS-stimulated HMGB1
      nucleocytoplasmic translocation and extracellular release. Furthermore, silencing
      CD11b interrupted the interaction of HMGB1 with either a nuclear export factor
      chromosome region maintenance 1 or classical protein kinase C and inhibited
      classical protein kinase C-induced HMGB1 phosphorylation, the potential
      underlying mechanism(s) responsible for CD11b blockage-induced suppression of
      HMGB1 nucleocytoplasmic translocation and subsequent extracellular release. Thus,
      our results highlight that CD11b contributes to the development of sepsis,
      predominantly by facilitating nucleocytoplasmic translocation and active release
      of HMGB1.

PMID- 29343554
TI  - Biased Generation and In Situ Activation of Lung Tissue-Resident Memory CD4 T
      Cells in the Pathogenesis of Allergic Asthma.
AB  - Asthma is a chronic inflammatory disease mediated by allergen-specific CD4 T
      cells that promote lung inflammation through recruitment of cellular effectors
      into the lung. A subset of lung T cells can persist as tissue-resident memory T
      cells (TRMs) following infection and allergen induction, although the generation
      and role of TRM in asthma persistence and pathogenesis remain unclear. In this
      study, we used a mouse model of chronic exposure to intranasal house dust mite
      (HDM) extract to dissect how lung TRMs are generated and function in the
      persistence and pathogenesis of allergic airway disease. We demonstrate that both
      CD4+ and CD8+ T cells infiltrate into the lung tissue during acute HDM exposure;
      however, only CD4+ TRMs, and not CD8+ TRMs, persist long term following cessation
      of HDM administration. Lung CD4+ TRMs are localized around airways and are
      rapidly reactivated upon allergen re-exposure accompanied by the rapid induction
      of airway hyperresponsiveness independent of circulating T cells. Lung CD4+ TRM
      activation to HDM challenge is also accompanied by increased recruitment and
      activation of dendritic cells in the lungs. Our results indicate that lung CD4+
      TRMs can perpetuate allergen-specific sensitization and direct early inflammatory
      signals that promote rapid lung pathology, suggesting that targeting lung CD4+
      TRMs could have therapeutic benefit in alleviating recurrent asthma episodes.

PMID- 29343556
TI  - RASA1/NF1-Mutant Lung Cancer: Racing to the Clinic?
AB  - Although mutation of NF1 has been described in non-small cell lung cancer
      (NSCLC), co-mutation with RASA1, another Ras-GTPase activating protein (RasGAP),
      defines a novel genetically defined subclass of NSCLC. RASA1/NF1-mutant cell
      lines are highly sensitive to MEK inhibitors, warranting clinical evaluation of
      MAPK inhibition in this subclass of patients. Clin Cancer Res; 24(6); 1243-5.
      (c)2018 AACRSee related article by Hayashi et al., p. 1436.

PMID- 29343558
TI  - Postcranial diversity and recent ecomorphic impoverishment of North American gray
      wolves.
AB  - Recent advances in genomics and palaeontology have begun to unravel the complex
      evolutionary history of the gray wolf, Canis lupus Still, much of their
      phenotypic variation across time and space remains to be documented. We examined
      the limb morphology of the fossil and modern North American gray wolves from the
      late Quaternary (<ca 70 ka) to better understand their postcranial diversity
      through time. We found that the late-Pleistocene gray wolves were characterized
      by short-leggedness on both sides of the Cordilleran-Laurentide ice sheets, and
      that this trait survived well into the Holocene despite the collapse of
      Pleistocene megafauna and disappearance of the 'Beringian wolf' from Alaska. By
      contrast, extant populations in the Midwestern USA and northwestern North America
      are distinguished by their elongate limbs with long distal segments, which appear
      to have evolved during the Holocene possibly in response to a new level or type
      of prey depletion. One of the consequences of recent extirpation of the Plains
      (Canis lupus nubilus) and Mexican wolves (C. l. baileyi) from much of the USA is
      an unprecedented loss of postcranial diversity through removal of short-legged
      forms. Conservation of these wolves is thus critical to restoration of the
      ecophenotypic diversity and evolutionary potential of gray wolves in North
      America.

PMID- 29343557
TI  - DICER1 and Associated Conditions: Identification of At-risk Individuals and
      Recommended Surveillance Strategies.
AB  - Pathogenic germline DICER1 variants cause a hereditary cancer predisposition
      syndrome with a variety of manifestations. In addition to conferring increased
      cancer risks for pleuropulmonary blastoma (PPB) and ovarian sex cord-stromal
      tumors, particularly Sertoli-Leydig cell tumor, individuals with pathogenic
      germline DICER1 variants may also develop lung cysts, cystic nephroma, renal
      sarcoma and Wilms tumor, nodular hyperplasia of the thyroid, nasal
      chondromesenchymal hamartoma, ciliary body medulloepithelioma, genitourinary
      embryonal rhabdomyosarcoma, and brain tumors including pineoblastoma and
      pituitary blastoma. In May 2016, the International PPB Registry convened the
      inaugural International DICER1 Symposium to develop consensus testing and
      surveillance and treatment recommendations. Attendees from North America, Europe,
      and Russia provided expert representation from the disciplines of pediatric
      oncology, endocrinology, genetics, genetic counseling, radiology, pediatric
      surgery, pathology, and clinical research. Recommendations are provided for
      genetic testing; prenatal management; and surveillance for DICER1-associated
      pulmonary, renal, gynecologic, thyroid, ophthalmologic, otolaryngologic, and
      central nervous system tumors and gastrointestinal polyps. Risk for most DICER1
      associated neoplasms is highest in early childhood and decreases in adulthood.
      Individual and caregiver education and judicious imaging-based surveillance are
      the primary recommended approaches. These testing and surveillance
      recommendations reflect a consensus of expert opinion and current literature. As
      DICER1 research expands, guidelines for screening and treatment will continue to
      be updated. Clin Cancer Res; 24(10); 2251-61. (c)2018 AACR.

PMID- 29343559
TI  - A genetic locus for paranoia.
AB  - The psychological effects of brain-expressed imprinted genes in humans are
      virtually unknown. Prader-Willi syndrome (PWS) is a neurogenetic condition
      mediated by genomic imprinting, which involves high rates of psychosis
      characterized by hallucinations and paranoia, as well as autism. Altered
      expression of two brain-expressed imprinted genes, MAGEL2 and NDN, mediates a
      suite of PWS-related phenotypes, including behaviour, in mice. We phenotyped a
      large population of typical individuals for schizophrenia-spectrum and autism
      spectrum traits, and genotyped them for the single-nucleotide polymorphism
      rs850807, which is putatively functional and linked with MAGEL2 and NDN Genetic
      variation in rs850807 was strongly and exclusively associated with the ideas of
      reference subscale of the schizophrenia spectrum, which is best typified as
      paranoia. These findings provide a single-locus genetic model for analysing the
      neurological and psychological bases of paranoid thinking, and implicate
      imprinted genes, and genomic conflicts, in human mentalistic thought.

PMID- 29343560
TI  - Primate social group sizes exhibit a regular scaling pattern with natural
      attractors.
AB  - Primate groups vary considerably in size across species. Nonetheless, the
      distribution of mean species group size has a regular scaling pattern with
      preferred sizes approximating 2.5, 5, 15, 30 and 50 individuals (although
      strepsirrhines lack the latter two), with a scaling ratio of approximately 2.5
      similar to that observed in human social networks. These clusters appear to form
      distinct social grades that are associated with rapid evolutionary change,
      presumably in response to intense environmental selection pressures. These
      findings may have wider implications for other highly social mammal taxa.

PMID- 29343561
TI  - Geographical range size and latitude predict population genetic structure in a
      global survey.
AB  - While genetic diversity within species is influenced by both geographical
      distance and environmental gradients, it is unclear what other factors are likely
      to promote population genetic structure. Using a machine learning framework and
      georeferenced DNA sequences from more than 8000 species, we demonstrate that
      geographical attributes of the species range, including total size, latitude and
      elevation, are the most important predictors of which species are likely to
      contain structured genetic variation. While latitude is well known as an
      important predictor of biodiversity, our work suggests that it also plays a key
      role in shaping diversity within species.

PMID- 29343562
TI  - High-quality fossil dates support a synchronous, Late Holocene extinction of
      devils and thylacines in mainland Australia.
AB  - The last large marsupial carnivores-the Tasmanian devil (Sarcophilis harrisii)
      and thylacine (Thylacinus cynocephalus)-went extinct on mainland Australia during
      the mid-Holocene. Based on the youngest fossil dates (approx. 3500 years before
      present, BP), these extinctions are often considered synchronous and driven by a
      common cause. However, many published devil dates have recently been rejected as
      unreliable, shifting the youngest mainland fossil age to 25 500 years BP and
      challenging the synchronous-extinction hypothesis. Here we provide 24 and 20 new
      ages for devils and thylacines, respectively, and collate existing, reliable
      radiocarbon dates by quality-filtering available records. We use this new dataset
      to estimate an extinction time for both species by applying the Gaussian
      resampled, inverse-weighted McInerney (GRIWM) method. Our new data and analysis
      definitively support the synchronous-extinction hypothesis, estimating that the
      mainland devil and thylacine extinctions occurred between 3179 and 3227 years BP.

PMID- 29343563
TI  - Robotic crabs reveal that female fiddler crabs are sensitive to changes in male
      display rate.
AB  - Males often produce dynamic, repetitive courtship displays that can be demanding
      to perform and might advertise male quality to females. A key feature of
      demanding displays is that they can change in intensity: escalating as a male
      increases his signalling effort, but de-escalating as a signaller becomes
      fatigued. Here, we investigated whether female fiddler crabs, Uca mjoebergi, are
      sensitive to changes in male courtship wave rate. We performed playback
      experiments using robotic male crabs that had the same mean wave rate, but either
      escalated, de-escalated or remained constant. Females demonstrated a strong
      preference for escalating robots, but showed mixed responses to robots that de
      escalated ('fast' to 'slow') compared to those that waved at a constant 'medium'
      rate. These findings demonstrate that females can discern changes in male display
      rate, and prefer males that escalate, but that females are also sensitive to past
      display rates indicative of prior vigour.

PMID- 29343564
TI  - Phenotypic plasticity in an ant with strong caste-genotype association.
AB  - Caste determination in social Hymenoptera (whether a female egg develops into a
      reproductive queen or a sterile worker) is a remarkable example of phenotypic
      plasticity where females with highly similar genomes exhibit striking differences
      in morphology and behaviour. This phenotypic dichotomy is typically influenced by
      environmental factors. However, recent studies have revealed a strong caste
      genotype association in hybridogenetic ants: workers are all interlineage hybrids
      while queens are all purebred, suggesting that female caste fate is genetically
      determined. Using the hybridogenetic ant Cataglyphis mauritanica, we show that
      under laboratory conditions, purebred offspring develop into reproductive queens
      but occasionally give rise to workers. Moreover, while hybrids typically become
      workers, juvenile hormone treatment can switch their developmental pathway to the
      reproductive caste. These results indicate that phenotypic plasticity has been
      retained in an ant with a strong caste-genotype association, despite its lack of
      expression in natural conditions.

PMID- 29343565
TI  - Inverted intergeneric introgression between critically endangered kipunjis and
      yellow baboons in two disjunct populations.
AB  - Intergeneric hybridization and introgression was reported from one of two
      populations of the recently discovered kipunji (Rungwecebus kipunji), a
      critically endangered African monkey species of southern Tanzania. Kipunjis of
      the introgressed population (from Mount Rungwe) carry a mitochondrial DNA (mtDNA)
      haplotype closely related to those of parapatric yellow baboons (Papio
      cynocephalus), whereas the second kipunji population, in the Udzungwa Mountains,
      carries the original kipunji mtDNA haplotypes, which diverged from the baboon
      lineage about 3 million years ago. Interestingly, in our study of yellow baboons
      in Tanzania, we found that baboons from the southeastern boundary of the Udzungwa
      Mountains carry mtDNA haplotypes closely related to the original kipunji
      haplotype, whereas baboons from the northern boundary, as expected, carry mtDNA
      haplotypes of the northern yellow baboon clade. These findings provide evidence
      for a case of inverted intergeneric admixture in primates: (i) a baboon mtDNA
      haplotype introgressed the Mount Rungwe kipunji population by mitochondrial
      capture and (ii) an Udzungwa Mountains kipunji mtDNA haplotype introgressed a
      small subpopulation of yellow baboons by either mitochondrial capture or nuclear
      swamping. The baboon-kipunji example therefore constitutes an interesting system
      for further studies of the effects of genetic admixture on fitness and
      speciation.

PMID- 29343566
TI  - Attenuation of Simian Varicella Virus Infection by Enhanced Green Fluorescent
      Protein in Rhesus Macaques.
AB  - Simian varicella virus (SVV), the primate counterpart of varicella-zoster virus,
      causes varicella (chickenpox), establishes latency in ganglia, and reactivates to
      produce zoster. We previously demonstrated that a recombinant SVV expressing
      enhanced green fluorescent protein (rSVV.eGFP) is slightly attenuated both in
      culture and in infected monkeys. Here, we generated two additional recombinant
      SVVs to visualize infected cells in vitro and in vivo One harbors eGFP fused to
      the N terminus of open reading frame 9 (ORF9) (rSVV.eGFP-2a-ORF9), and another
      harbors eGFP fused to the C terminus of ORF66 (rSVV.eGFP-ORF66). Both recombinant
      viruses efficiently expressed eGFP in cultured cells. Both recombinant SVV
      infections in culture were comparable to that of wild-type SVV (SVV.wt). Unlike
      SVV.wt, eGFP-tagged SVV did not replicate in rhesus cells in culture.
      Intratracheal (i.t.) or i.t. plus intravenous (i.v.) inoculation of rhesus
      macaques with these new eGFP-tagged viruses resulted in low viremia without
      varicella rash, although SVV DNA was abundant in bronchoalveolar lavage (BAL)
      fluid at 10 days postinoculation (dpi). SVV DNA was also found in trigeminal
      ganglia of one monkey inoculated with rSVV.eGFP-ORF66. Intriguingly, a humoral
      response to both SVV and eGFP was observed. In addition, monkeys inoculated with
      the eGFP-expressing viruses were protected from superinfection with SVV.wt,
      suggesting that the monkeys had mounted an efficient immune response. Together,
      our results show that eGFP expression could be responsible for their reduced
      pathogenesis.IMPORTANCE SVV infection in nonhuman primates has served as an
      extremely useful animal model to study varicella-zoster virus (VZV) pathogenesis.
      eGFP-tagged viruses are a great tool to investigate their pathogenesis. We
      constructed and tested two new recombinant SVVs with eGFP inserted into two
      different locations in the SVV genome. Both recombinant SVVs showed robust
      replication in culture but reduced viremia compared to that with SVV.wt during
      primary infection in rhesus macaques. Our results indicate that conclusions on
      eGFP-tagged viruses based on in vitro results should be handled with care, since
      eGFP expression could result in attenuation of the virus.

PMID- 29343567
TI  - Parainfluenza Virus Infection Sensitizes Cancer Cells to DNA-Damaging Agents:
      Implications for Oncolytic Virus Therapy.
AB  - A parainfluenza virus 5 (PIV5) with mutations in the P/V gene (P/V-CPI-) is
      restricted for spread in normal cells but not in cancer cells in vitro and is
      effective at reducing tumor burdens in mouse model systems. Here we show that P/V
      CPI- infection of HEp-2 human laryngeal cancer cells results in the majority of
      the cells dying, but unexpectedly, over time, there is an emergence of a
      population of cells that survive as P/V-CPI- persistently infected (PI) cells.
      P/V-CPI- PI cells had elevated levels of basal caspase activation, and viability
      was highly dependent on the activity of cellular inhibitor-of-apoptosis proteins
      (IAPs) such as Survivin and XIAP. In challenge experiments with external inducers
      of apoptosis, PI cells were more sensitive to cisplatin-induced DNA damage and
      cell death. This increased cisplatin sensitivity correlated with defects in DNA
      damage signaling pathways such as phosphorylation of Chk1 and translocation of
      damage-specific DNA binding protein 1 (DDB1) to the nucleus. Cisplatin-induced
      killing of PI cells was sensitive to the inhibition of wild-type (WT) p53
      inducible protein 1 (WIP1), a phosphatase which acts to terminate DNA damage
      signaling pathways. A similar sensitivity to cisplatin was seen with cells during
      acute infection with P/V-CPI- as well as during acute infections with WT PIV5 and
      the related virus human parainfluenza virus type 2 (hPIV2). Our results have
      general implications for the design of safer paramyxovirus-based vectors that
      cannot establish PI as well as the potential for combining chemotherapy with
      oncolytic RNA virus vectors.IMPORTANCE There is intense interest in developing
      oncolytic viral vectors with increased potency against cancer cells, particularly
      those cancer cells that have gained resistance to chemotherapies. We have found
      that infection with cytoplasmically replicating parainfluenza virus can result in
      increases in the killing of cancer cells by agents that induce DNA damage, and
      this is linked to alterations to DNA damage signaling pathways that balance cell
      survival versus death. Our results have general implications for the design of
      safer paramyxovirus-based vectors that cannot establish persistent infection, the
      repurposing of drugs that target cellular IAPs as antivirals, and the combined
      use of DNA-damaging chemotherapy agents in conjunction with oncolytic RNA virus
      vectors.

PMID- 29343568
TI  - An Alternate Route for Adeno-associated Virus (AAV) Entry Independent of AAV
      Receptor.
AB  - Determinants and mechanisms of cell attachment and entry steer adeno-associated
      virus (AAV) in its utility as a gene therapy vector. Thus far, a systematic
      assessment of how diverse AAV serotypes engage their proteinaceous receptor AAVR
      (KIAA0319L) to establish transduction has been lacking, despite potential
      implications for cell and tissue tropism. Here, a large set of human and simian
      AAVs as well as in silico-reconstructed ancestral AAV capsids were interrogated
      for AAVR usage. We identified a distinct AAV capsid lineage comprised of AAV4 and
      AAVrh32.33 that can bind and transduce cells in the absence of AAVR, independent
      of the multiplicity of infection. Virus overlay assays and rescue experiments in
      nonpermissive cells demonstrate that these AAVs are unable to bind to or use the
      AAVR protein for entry. Further evidence for a distinct entry pathway was
      observed in vivo, as AAVR knockout mice were equally as permissive to
      transduction by AAVrh32.33 as wild-type mice upon systemic injection. We
      interestingly observe that some AAV capsids undergo a low level of transduction
      in the absence of AAVR, both in vitro and in vivo, suggesting that some capsids
      may have a multimodal entry pathway. In aggregate, our results demonstrate that
      AAVR usage is conserved among all primate AAVs except for those of the AAV4
      lineage, and a non-AAVR pathway may be available to other serotypes. This work
      furthers our understanding of the entry of AAV, a vector system of broad utility
      in gene therapy.IMPORTANCE Adeno-associated virus (AAV) is a nonpathogenic virus
      that is used as a vehicle for gene delivery. Here, we have identified several
      situations in which transduction is retained in both cell lines and a mouse model
      in the absence of a previously defined entry receptor, AAVR. Defining the
      molecular determinants of the infectious pathway of this highly relevant viral
      vector system can help refine future applications and therapies with this vector.

PMID- 29343569
TI  - Myxoma Virus M083 Is a Virulence Factor Which Mediates Systemic Dissemination.
AB  - Poxviruses are large, DNA viruses whose protein capsid is surrounded by one or
      more lipid envelopes. Embedded into these lipid envelopes are three conserved
      viral proteins which are thought to mediate binding of virions to target cells.
      While the function of these proteins has been studied in vitro, their specific
      roles during the pathogenesis of poxviral disease remain largely unclear. Here we
      present data demonstrating that the putative chondroitin binding protein M083
      from the leporipoxvirus myxoma virus is a significant virulence factor during
      infection of susceptible Oryctolagus rabbits. Removal of M083 results in a
      reduced capacity of virus to spread beyond the regional lymph nodes and
      completely eliminates infection-mediated mortality. In vitro, removal of M083
      results in only minor intracellular replication defects but causes a significant
      reduction in the ability of myxoma virus to spread from infected epithelial cells
      onto primary lymphocytes. We hypothesize that the physiological role of M083 is
      therefore to mediate the spread of myxoma virus onto rabbit lymphocytes, allowing
      these cells to disseminate virus throughout infected rabbits.IMPORTANCE
      Poxviruses represent both a class of human pathogens and potential therapeutic
      agents for the treatment of human malignancy. Understanding the basic biology of
      these agents is therefore significant to human health in a variety of ways. While
      the mechanisms mediating poxviral binding have been well studied in vitro, how
      these mechanisms impact poxviral pathogenesis in vivo remains unclear. The
      current study advances our understanding of how poxviral binding impacts viral
      pathogenesis by demonstrating that the putative chondroitin binding protein M083
      plays a critical role during the pathogenesis of myxoma virus in susceptible
      Oryctolagus rabbits by impacting viral dissemination through changes in the
      transfer of virions onto primary splenocytes.

PMID- 29343570
TI  - Roles of the 5' Untranslated Region of Nonprimate Hepacivirus in Translation
      Initiation and Viral Replication.
AB  - The 5' untranslated region (UTR) of hepatitis C virus (HCV), which is composed of
      four domains (I, II, III, and IV) and a pseudoknot, is essential for translation
      and viral replication. Equine nonprimate hepacivirus (EHcV) harbors a 5' UTR
      consisting of a large 5'-terminal domain (I); three additional domains (I', II,
      and III), which are homologous to domains I, II, and III, respectively, of HCV;
      and a pseudoknot, in the order listed. In this study, we investigated the roles
      of the EHcV 5' UTR in translation and viral replication. The internal ribosome
      entry site (IRES) activity of the EHcV 5' UTR was lower than that of the HCV 5'
      UTR in several cell lines due to structural differences in domain III. Domains I
      and III of EHcV were functional in the HCV 5' UTR in terms of IRES activity and
      the replication of the subgenomic replicon (SGR), although domain II was not
      exchangeable between EHcV and HCV for SGR replication. Furthermore, the region
      spanning domains I and I' of EHcV (the 5'-proximal EHcV-specific region) improved
      RNA stability and provided the HCV SGR with microRNA 122 (miR-122)-independent
      replication capability, while EHcV domain I alone improved SGR replication and
      RNA stability irrespective of miR-122. These data suggest that the region
      spanning EHcV domains I and I' improves RNA stability and viral replication
      regardless of miR-122 expression. The 5'-proximal EHcV-specific region may
      represent an inherent mechanism to facilitate viral replication in nonhepatic
      tissues.IMPORTANCE EHcV is the closest viral homolog to HCV among other
      hepaciviruses. HCV exhibits a narrow host range and liver-specific tropism, while
      epidemiological reports suggest that EHcV infects the liver and respiratory
      organs in horses, donkeys, and dogs. However, the mechanism explaining the
      differences in host or organ tropism between HCV and EHcV is unknown. In this
      study, our data suggest that the 5' untranslated region (UTR) of EHcV is composed
      of an internal ribosome entry site (IRES) element that is functionally
      exchangeable with HCV IRES elements. Furthermore, the 5'-proximal EHcV-specific
      region enhances viral replication and RNA stability in a miR-122-independent
      manner. Our data suggest that the region upstream of domain II in the EHcV 5' UTR
      contributes to the differences in tissue tropism observed between these
      hepaciviruses.

PMID- 29343571
TI  - Casein Kinase 1alpha Mediates the Degradation of Receptors for Type I and Type II
      Interferons Caused by Hemagglutinin of Influenza A Virus.
AB  - Although influenza A virus (IAV) evades cellular defense systems to effectively
      propagate in the host, the viral immune-evasive mechanisms are incompletely
      understood. Our recent data showed that hemagglutinin (HA) of IAV induces
      degradation of type I IFN receptor 1 (IFNAR1). Here, we demonstrate that IAV HA
      induces degradation of type II IFN (IFN-gamma) receptor 1 (IFNGR1), as well as
      IFNAR1, via casein kinase 1alpha (CK1alpha), resulting in the impairment of
      cellular responsiveness to both type I and II IFNs. IAV infection or transient HA
      expression induced degradation of both IFNGR1 and IFNAR1, whereas HA gene
      deficient IAV failed to downregulate the receptors. IAV HA caused the
      phosphorylation and ubiquitination of IFNGR1, leading to the lysosome-dependent
      degradation of IFNGR1. Influenza viral HA strongly decreased cellular sensitivity
      to type II IFNs, as it suppressed the activation of STAT1 and the induction of
      IFN-gamma-stimulated genes in response to exogenously supplied recombinant IFN
      gamma. Importantly, CK1alpha, but not p38 MAP kinase or protein kinase D2, was
      proven to be critical for HA-induced degradation of both IFNGR1 and IFNAR1.
      Pharmacologic inhibition of CK1alpha or small interfering RNA (siRNA)-based
      knockdown of CK1alpha repressed the degradation processes of both IFNGR1 and
      IFNAR1 triggered by IAV infection. Further, CK1alpha was shown to be pivotal for
      proficient replication of IAV. Collectively, the results suggest that IAV HA
      induces degradation of IFN receptors via CK1alpha, creating conditions favorable
      for viral propagation. Therefore, the study uncovers a new immune-evasive pathway
      of influenza virus.IMPORTANCE Influenza A virus (IAV) remains a grave threat to
      humans, causing seasonal and pandemic influenza. Upon infection, innate and
      adaptive immunity, such as the interferon (IFN) response, is induced to protect
      hosts against IAV infection. However, IAV seems to be equipped with tactics to
      evade the IFN-mediated antiviral responses, although the detailed mechanisms need
      to be elucidated. In the present study, we show that IAV HA induces the
      degradation of the type II IFN receptor IFNGR1 and thereby substantially
      attenuates cellular responses to IFN-gamma. Of note, a cellular kinase, casein
      kinase 1alpha (CK1alpha), is crucial for IAV HA-induced degradation of both
      IFNGR1 and IFNAR1. Accordingly, CK1alpha is proven to positively regulate IAV
      propagation. Thus, this study unveils a novel strategy employed by IAV to evade
      IFN-mediated antiviral activities. These findings may provide new insights into
      the interplay between IAV and host immunity to impact influenza virus
      pathogenicity.

PMID- 29343572
TI  - Gammaherpesvirus Colonization of the Spleen Requires Lytic Replication in B
      Cells.
AB  - Gammaherpesviruses infect lymphocytes and cause lymphocytic cancers. Murid
      herpesvirus-4 (MuHV-4), Epstein-Barr virus, and Kaposi's sarcoma-associated
      herpesvirus all infect B cells. Latent infection can spread by B cell
      recirculation and proliferation, but whether this alone achieves systemic
      infection is unclear. To test the need of MuHV-4 for lytic infection in B cells,
      we flanked its essential ORF50 lytic transactivator with loxP sites and then
      infected mice expressing B cell-specific Cre (CD19-Cre). The floxed virus
      replicated normally in Cre- mice. In CD19-Cre mice, nasal and lymph node
      infections were maintained; but there was little splenomegaly, and splenic virus
      loads remained low. Cre-mediated removal of other essential lytic genes gave a
      similar phenotype. CD19-Cre spleen infection by intraperitoneal virus was also
      impaired. Therefore, MuHV-4 had to emerge lytically from B cells to colonize the
      spleen. An important role for B cell lytic infection in host colonization is
      consistent with the large CD8+ T cell responses made to gammaherpesvirus lytic
      antigens during infectious mononucleosis and suggests that vaccine-induced
      immunity capable of suppressing B cell lytic infection might reduce long-term
      virus loads.IMPORTANCE Gammaherpesviruses cause B cell cancers. Most models of
      host colonization derive from cell cultures with continuous, virus-driven B cell
      proliferation. However, vaccines based on these models have worked poorly. To
      test whether proliferating B cells suffice for host colonization, we inactivated
      the capacity of MuHV-4, a gammaherpesvirus of mice, to reemerge from B cells. The
      modified virus was able to colonize a first wave of B cells in lymph nodes but
      spread poorly to B cells in secondary sites such as the spleen. Consequently,
      viral loads remained low. These results were consistent with virus-driven B cell
      proliferation exploiting normal host pathways and thus having to transfer
      lytically to new B cells for new proliferation. We conclude that viral lytic
      infection is a potential target to reduce B cell proliferation.

PMID- 29343573
TI  - Porcine Mx1 Protein Inhibits Classical Swine Fever Virus Replication by Targeting
      Nonstructural Protein NS5B.
AB  - Mx proteins are interferon (IFN)-induced GTPases that have broad antiviral
      activity against a wide range of RNA and DNA viruses; they belong to the dynamin
      superfamily of large GTPases. In this study, we confirmed the anti-classical
      swine fever virus (CSFV) activity of porcine Mx1 in vitro and showed that porcine
      Mx2 (poMx2), human MxA (huMxA), and mouse Mx1 (mmMx1) also have anti-CSFV
      activity in vitro Small interfering RNA (siRNA) experiments revealed that
      depletion of endogenous poMx1 or poMx2 enhanced CSFV replication, suggesting that
      porcine Mx proteins are responsible for the antiviral activity of interferon
      alpha (IFN-alpha) against CSFV infection. Confocal microscopy,
      immunoprecipitation, glutathione S-transferase (GST) pulldown, and bimolecular
      fluorescence complementation (BiFC) demonstrated that poMx1 associated with NS5B,
      the RNA-dependent RNA polymerase (RdRp) of CSFV. We used mutations in the poMx1
      protein to elucidate the mechanism of their anti-CSFV activity and found that
      mutants that disrupted the association with NS5B lost all anti-CSV activity.
      Moreover, an RdRp activity assay further revealed that poMx1 undermined the RdRp
      activities of NS5B. Together, these results indicate that porcine Mx proteins
      exert their antiviral activity against CSFV by interacting with NS5B.IMPORTANCE
      Our previous studies have shown that porcine Mx1 (poMx1) inhibits classical swine
      fever virus (CSFV) replication in vitro and in vivo, but the molecular mechanism
      of action remains largely unknown. In this study, we dissect the molecular
      mechanism of porcine Mx1 and Mx2 against CSFV in vitro Our results show that
      poMx1 associates with NS5B, the RNA-dependent RNA polymerase of CSFV, resulting
      in the reduction of CSFV replication. Moreover, the mutants of poMx1 further
      elucidate the mechanism of their anti-CSFV activities.

PMID- 29343574
TI  - Novel Human Polyomavirus Noncoding Control Regions Differ in Bidirectional Gene
      Expression according to Host Cell, Large T-Antigen Expression, and Clinically
      Occurring Rearrangements.
AB  - Human polyomavirus (HPyV) DNA genomes contain three regions denoted the early
      viral gene region (EVGR), encoding the regulatory T-antigens and one microRNA,
      the late viral gene region (LVGR), encoding the structural Vp capsid proteins,
      and the noncoding control region (NCCR). The NCCR harbors the origin of viral
      genome replication and bidirectional promoter/enhancer functions governing EVGR
      and LVGR expression on opposite DNA strands. Despite principal similarities, HPyV
      NCCRs differ in length, sequence, and architecture. To functionally compare HPyV
      NCCRs, sequences from human isolates were inserted into a bidirectional reporter
      vector using dsRed2 for EVGR expression and green fluorescent protein (GFP) for
      LVGR expression. Transfecting HPyV NCCR reporter vectors into human embryonic
      kidney 293 (HEK293) cells and flow cytometry normalized to archetype BKPyV NCCR
      revealed a hierarchy of EVGR expression levels with MCPyV, HPyV12, and STLPyV
      NCCRs conferring stronger levels and HPyV6, HPyV9, and HPyV10 NCCRs weaker
      levels, while LVGR expression was less variable and showed comparable activity
      levels. Transfection of HEK293T cells expressing simian virus 40 (SV40) large T
      antigen (LTag) increased EVGR expression for most HPyV NCCRs, which correlated
      with the number of LTag-binding sites (Spearman's r, 0.625; P < 0.05) and
      decreased following SV40 LTag small interfering RNA (siRNA) knockdown. LTag
      dependent activation was specifically confirmed for two different MCPyV NCCRs in
      293MCT cells expressing the cognate MCPyV LTag. HPyV NCCR expression in different
      cell lines derived from skin (A375), cervix (HeLaNT), lung (A549), brain (Hs683),
      and colon (SW480) demonstrated that host cell properties significantly modulate
      the baseline HPyV NCCR activity, which partly synergized with SV40 LTag
      expression. Clinically occurring NCCR sequence rearrangements of HPyV7 PITT-1 and
      -2 and HPyV9 UF1 were found to increase EVGR expression compared to the
      respective HPyV archetype, but this was partly host cell type specific.IMPORTANCE
      HPyV NCCRs integrate essential viral functions with respect to host cell
      specificity, persistence, viral replication, and disease. Here, we show that HPyV
      NCCRs not only differ in sequence length, number, and position of LTag- and
      common transcription factor-binding sites but also confer differences in
      bidirectional viral gene expression. Importantly, EVGR reporter expression was
      significantly modulated by LTag expression and by host cell properties. Clinical
      sequence variants of HPyV7 and HPyV9 NCCRs containing deletions and insertions
      were associated with increased EVGR expression, similar to BKPyV and JCPyV
      rearrangements, emphasizing that HPyV NCCR sequences are major determinants not
      only of host cell tropism but also of pathogenicity. These results will help to
      define secondary HPyV cell tropism beyond HPyV surface receptors, to identify key
      viral and host factors shaping the viral life cycle, and to develop preclinical
      models of HPyV persistence and replication and suitable antiviral targets.

PMID- 29343575
TI  - High-Resolution Sequencing of Viral Populations during Early Simian
      Immunodeficiency Virus Infection Reveals Evolutionary Strategies for Rapid Escape
      from Emerging Env-Specific Antibody Responses.
AB  - Primate lentiviruses, including the human and simian immunodeficiency viruses
      (HIV and SIV), produce infections marked by persistent, ongoing viral
      replication. This occurs despite the presence of virus-specific adaptive immune
      responses, including antibodies targeting the viral envelope glycoprotein (Env),
      and evolution of antibody-escape variants is a well-documented feature of
      lentiviral infection. Here, we examined the evolutionary dynamics of the SIV env
      gene during early infection (<=29 weeks postinfection) in a cohort of four
      SIVmac251-infected rhesus macaques. We tracked env evolution during acute and
      early infection using frequent sampling and ultradeep sequencing of viral
      populations, capturing a transmission bottleneck and the subsequent
      reestablishment of Env diversity. A majority of changes in the gp120 subunit
      mapped to two short clusters, one in the first variable region (V1) and one in
      V4, while most changes in the gp41 subunit appeared in the cytoplasmic domain.
      Variation in V1 was dominated by short duplications and deletions of repetitive
      sequence, while variation in V4 was marked by short in-frame deletions and
      closely overlapping substitutions. The most common substitutions in both patches
      did not alter viral replicative fitness when tested using a highly sensitive,
      deep-sequencing-based competition assay. Our results, together with the
      observation that very similar or identical patterns of sequence evolution also
      occur in different macaque species infected with related but divergent strains of
      SIV, suggest that resistance to early, strain-specific anti-Env antibodies is the
      result of temporally and mutationally predictable pathways of escape that occur
      during the early stages of infection.IMPORTANCE The envelope glycoprotein (Env)
      of primate lentiviruses mediates entry by binding to host cell receptors followed
      by fusion of the viral membrane with the cell membrane. The exposure of Env
      complexes on the surface of the virion results in targeting by antibodies,
      leading to selection for virus escape mutations. We used the SIV/rhesus macaque
      model to track in vivo evolution of variation in Env during acute/early infection
      in animals with and without antibody responses to Env, uncovering remarkable
      variation in animals with antibody responses within weeks of infection. Using a
      deep-sequencing-based fitness assay, we found substitutions associated with
      antibody escape had little to no effect on inherent replicative capacity. The
      ability to readily propagate advantageous changes that incur little to no
      replicative fitness costs may be a mechanism to maintain continuous replication
      under constant immune selection, allowing the virus to persist for months to
      years in the infected host.

PMID- 29343576
TI  - Increased epitope complexity correlated with antibody affinity maturation and a
      novel binding mode revealed by structures of rabbit antibodies against the third
      variable loop (V3) of HIV-1 gp120.
AB  - The V3 loop of HIV-1 gp120 is an immunodominant region targeted by neutralizing
      antibodies (nAbs). Despite limited breadth, better characterization of the
      structural details of the interactions between these nAbs and their target
      epitopes would enhance our understanding of the mechanism of neutralization and
      facilitate designing better immunogens to induce nAbs with greater breadth.
      Recently, we isolated two anti-V3 neutralizing monoclonal antibodies (mAbs), 10A3
      and 10A37, from a rabbit immunized with gp120 of the M group consensus sequence.
      In this study, crystal structures of these mAbs bound to target epitopes were
      determined. 10A3 binds to the V3 crown (303TRKSIHIGPGRAF317), using the cradle
      binding mode similar to human V3 mAbs encoded by IGHV5-51 germline genes and its
      epitope structure resembles that bound to the human antibodies. In contrast,
      10A37, which exhibits greater breadth and potency than 10A3, binds the V3 crown
      and the succeeding stem region (308HIGPGRAFYTTGEI323). Unexpectedly, the
      315RAFYTT320 portion of the epitope existed as helical turns, a V3 structure that
      has not been observed previously. Its main chain-dominated antigen-antibody
      interactions not only explain the broad neutralization of 10A37 but also show
      that its epitope is a potential vaccine target to be further evaluated. In
      conclusion, our study provides novel insights about neutralization-susceptible
      epitope structures of the V3 loop of HIV-1 gp120 and demonstrates that, despite
      low amino acid sequence similarity from human antibody germline genes, rabbits
      can serve as a useful animal model to evaluate human vaccine
      candidates.IMPORTANCE The apex crown of the third variable loop (V3) of HIV-1
      gp120 is the most immunogenic region of the surface glycoprotein and many mAbs
      targeting this region have been developed. Structural understanding of V3 crown
      mAbs not only can help understand how antibody responses targeting this unique
      region, but also contribute to immunogen design for vaccine development. We
      present here crystal structures of two neutralizing V3 mAbs, 10A3 and 10A37,
      developed from rabbits immunized with gp120. Our analysis of 10A3 in complex with
      V3 provided a detailed example of how epitope complexity can evolve with affinity
      maturation, while that of 10A37 revealed a novel V3 binding mode targeting the C
      terminal side of V3 crown and showed that this region can form a helical
      structure. Our study provides novel insights about neutralization-susceptible V3
      epitope structures and demonstrates that rabbits can serve as a useful animal
      model to evaluate human vaccine candidates.

PMID- 29343577
TI  - Cellular and Humoral Immunity Protect against Vaginal Zika Virus Infection in
      Mice.
AB  - Zika virus (ZIKV), which can cause devastating disease in fetuses of infected
      pregnant women, can be transmitted by mosquito inoculation and sexual routes.
      Little is known about immune protection against sexually transmitted ZIKV. In
      this study, we show that previous infection through intravaginal or subcutaneous
      routes with a contemporary Brazilian strain of ZIKV can protect against
      subsequent intravaginal challenge with a homologous strain. Both routes of
      inoculation induced high titers of ZIKV-specific and neutralizing antibody in
      serum and the vaginal lumen. Virus-specific T cells were recruited to and
      retained in the female reproductive tract after intravaginal and subcutaneous
      ZIKV infection. Studies in mice with genetic or acquired deficiencies in B and/or
      T cells demonstrated that both lymphocyte populations redundantly protect against
      intravaginal challenge in ZIKV-immune animals. Passive transfer of ZIKV immune
      IgG or T cells significantly limited intravaginal infection of naive mice,
      although antibody more effectively prevented dissemination throughout the
      reproductive tract. Collectively, our experiments begin to establish the immune
      correlates of protection against intravaginal ZIKV infection, which should inform
      vaccination strategies in non-pregnant and pregnant women.IMPORTANCE The recent
      ZIKV epidemic resulted in devastating outcomes in fetuses and may affect
      reproductive health. Unlike other flaviviruses, ZIKV can be spread by sexual
      contact as well as a mosquito vector. While previous studies have identified
      correlates of protection for mosquito-mediated infection, few have focused on
      immunity against sexual transmission. As exposure to ZIKV via mosquito bite has
      likely occurred to many living in endemic areas, our study addresses whether this
      route of infection can protect against subsequent sexual exposure. We demonstrate
      that subcutaneous ZIKV infection can protect against subsequent vaginal infection
      by generating both local antiviral T cell and antibody responses. Our research
      begins to define the immune correlates of protection for ZIKV infection in the
      vagina and provides a foundation for testing ZIKV vaccines against sexual
      transmission.

PMID- 29343578
TI  - A New Quinoline BRD4 Inhibitor Targets a Distinct Latent HIV-1 Reservoir for
      Reactivation from Other "Shock" Drugs.
AB  - Upon HIV-1 infection, a reservoir of latently infected resting T cells prevents
      the eradication of the virus from patients. To achieve complete depletion, the
      existing virus-suppressing antiretroviral therapy must be combined with drugs
      that reactivate the dormant viruses. We previously described a novel chemical
      scaffold compound, MMQO (8-methoxy-6-methylquinolin-4-ol), that is able to
      reactivate viral transcription in several models of HIV latency, including J-Lat
      cells, through an unknown mechanism. MMQO potentiates the activity of known
      latency-reversing agents (LRAs) or "shock" drugs, such as protein kinase C (PKC)
      agonists or histone deacetylase (HDAC) inhibitors. Here, we demonstrate that MMQO
      activates HIV-1 independently of the Tat transactivator. Gene expression
      microarrays in Jurkat cells indicated that MMQO treatment results in robust
      immunosuppression, diminishes expression of c-Myc, and causes the dysregulation
      of acetylation-sensitive genes. These hallmarks indicated that MMQO mimics
      acetylated lysines of core histones and might function as a bromodomain and
      extraterminal domain protein family inhibitor (BETi). MMQO functionally mimics
      the effects of JQ1, a well-known BETi. We confirmed that MMQO interacts with the
      BET family protein BRD4. Utilizing MMQO and JQ1, we demonstrate how the
      inhibition of BRD4 targets a subset of latently integrated barcoded proviruses
      distinct from those targeted by HDAC inhibitors or PKC pathway agonists. Thus,
      the quinoline-based compound MMQO represents a new class of BET bromodomain
      inhibitors that, due to its minimalistic structure, holds promise for further
      optimization for increased affinity and specificity for distinct bromodomain
      family members and could potentially be of use against a variety of diseases,
      including HIV infection.IMPORTANCE The suggested "shock and kill" therapy aims to
      eradicate the latent functional proportion of HIV-1 proviruses in a patient.
      However, to this day, clinical studies investigating the "shocking" element of
      this strategy have proven it to be considerably more difficult than anticipated.
      While the proportion of intracellular viral RNA production and general plasma
      viral load have been shown to increase upon a shock regimen, the global viral
      reservoir remains unaffected, highlighting both the inefficiency of the
      treatments used and the gap in our understanding of viral reactivation in vivo
      Utilizing a new BRD4 inhibitor and barcoded HIV-1 minigenomes, we demonstrate
      that PKC pathway activators and HDAC and bromodomain inhibitors all target
      different subsets of proviral integration. Considering the fundamental
      differences of these compounds and the synergies displayed between them, we
      propose that the field should concentrate on investigating the development of
      combinatory shock cocktail therapies for improved reservoir reactivation.

PMID- 29343579
TI  - Identification of Poxvirus Genome Uncoating and DNA Replication Factors with
      Mutually Redundant Roles.
AB  - Genome uncoating is essential for replication of most viruses. For poxviruses,
      the process is divided into two stages: removal of the envelope, allowing early
      gene expression, and breaching of the core wall, allowing DNA release,
      replication, and late gene expression. Subsequent studies showed that the host
      proteasome and the viral D5 protein, which has an essential role in DNA
      replication, are required for vaccinia virus (VACV) genome uncoating. In a search
      for additional VACV uncoating proteins, we noted a report that described a defect
      in DNA replication and late expression when the gene encoding a 68-kDa ankyrin
      repeat/F-box protein (68k-ank), associated with the cellular SCF (Skp1, cullin1,
      F-box-containing complex) ubiquitin ligase complex, was deleted from the
      attenuated modified vaccinia virus Ankara (MVA). Here we showed that the 68k-ank
      deletion mutant exhibited diminished genome uncoating, formation of DNA
      prereplication sites, and degradation of viral cores as well as an additional,
      independent defect in DNA synthesis. Deletion of the 68k-ank homolog of VACV
      strain WR, however, was without effect, suggesting the existence of compensating
      genes. By inserting VACV genes into an MVA 68k-ank deletion mutant, we discovered
      that M2, a member of the poxvirus immune evasion (PIE) domain superfamily and a
      regulator of NF-kappaB, and C5, a member of the BTB/Kelch superfamily associated
      with cullin-3-based ligase complexes, independently rescued the 68k-ank deletion
      phenotype. Thus, poxvirus uncoating and DNA replication are intertwined processes
      involving at least three viral proteins with mutually redundant functions in
      addition to D5.IMPORTANCE Poxviruses comprise a family of large DNA viruses that
      infect vertebrates and invertebrates and cause diseases of medical and zoological
      importance. Poxviruses, unlike most other DNA viruses, replicate in the
      cytoplasm, and their large genomes usually encode 200 or more proteins with
      diverse functions. About 90 genes may be essential for chordopoxvirus replication
      based either on their conservation or individual gene deletion studies. However,
      this number may underestimate the true number of essential functions because of
      redundancy. Here we show that any one of three seemingly unrelated and
      individually nonessential proteins is required for the incompletely understood
      processes of genome uncoating and DNA replication, an example of synthetic
      lethality. Thus, poxviruses appear to have a complex genetic interaction network
      that has not been fully appreciated and which will require multifactor deletion
      screens to assess.

PMID- 29343580
TI  - Advancing Our Understanding of Protective Maternal Immunity as a Guide for
      Development of Vaccines To Reduce Congenital Cytomegalovirus Infections.
AB  - Human cytomegalovirus (HCMV) is the most common congenitally transmitted pathogen
      worldwide, impacting an estimated 1 million newborns annually. Congenital HCMV
      (cCMV) infection is a major global contributor to long-term neurologic deficits,
      including deafness, microcephaly, and neurodevelopmental delay, as well as to
      fetal loss and occasional infant mortality. Accordingly, design of a maternal
      vaccine to prevent cCMV continues to be a top public health priority.
      Nevertheless, we remain without a licensed vaccine. Maternal immunity provides
      partial protection, as the risk of vertical HCMV transmission from chronically
      infected mothers is reduced compared to settings in which the mother is newly
      infected during pregnancy. Therefore, an understanding of the maternal immune
      correlates of protection against cCMV is critical to informing design of an
      efficacious maternal vaccine. Although vaccine development is being assiduously
      pursued by a large number of pharmaceutical manufacturers, biotechnology
      organizations, and academic researchers, some pessimism has been expressed
      regarding the issue of whether a vaccine to protect against cCMV is possible.
      This pessimism is based on observations that natural immunity is not completely
      protective against maternal reinfection and congenital transmission. However, we
      assert that optimism regarding vaccine development is indeed justified, on the
      basis of accruing evidence of immune correlates of protection-readily achievable
      by vaccination-that are associated with reduced transmission of HCMV to the fetus
      in seronegative women. In light of the substantial burden on society conferred by
      cCMV infection, even a modest reduction in the occurrence of this fetal disease
      is an important public health goal and justifies aggressive clinical evaluation
      of vaccines currently in the pipeline.

PMID- 29343581
TI  - The 5' Untranslated Region of the Major Immediate Early mRNA Is Necessary for
      Efficient Human Cytomegalovirus Replication.
AB  - The human cytomegalovirus (HCMV) immediate early 1 (IE1) and IE2 proteins are
      critical regulators of virus replication. Both proteins are needed to efficiently
      establish lytic infection, and nascent expression of IE1 and IE2 is critical for
      reactivation from latency. The regulation of IE1 and IE2 protein expression is
      thus a central event in the outcome of HCMV infection. Transcription of the
      primary transcript encoding both IE1 and IE2 is well studied, but relatively
      little is known about the posttranscriptional mechanisms that control IE1 and IE2
      protein synthesis. The mRNA 5' untranslated region (5' UTR) plays an important
      role in regulating mRNA translation. Therefore, to better understand the control
      of IE1 and IE2 mRNA translation, we examined the role of the shared 5' UTR of the
      IE1 and IE2 mRNAs (MIE 5' UTR) in regulating translation. In a cell-free system,
      the MIE 5' UTR repressed translation, as predicted based on its length and
      sequence composition. However, in transfected cells we found that the MIE 5' UTR
      increased the expression of a reporter gene and enhanced its association with
      polysomes, demonstrating that the MIE 5' UTR has a positive role in translation
      control. We also found that the MIE 5' UTR was necessary for efficient IE1 and
      IE2 translation during infection. Replacing the MIE 5' UTR with an unstructured
      sequence of the same length decreased IE1 and IE2 protein expression despite
      similar levels of IE1 and IE2 mRNA and reduced the association of the IE1 and IE2
      mRNAs with polysomes. The wild-type MIE 5'-UTR sequence was also necessary for
      efficient HCMV replication. Together these data identify the shared 5' UTR of the
      IE1 and IE2 mRNAs as an important regulator of HCMV lytic replication.IMPORTANCE
      The HCMV IE1 and IE2 proteins are critical regulators of HCMV replication, both
      during primary infection and during reactivation from viral latency. Thus,
      defining factors that regulate IE1 and IE2 expression is important for
      understanding the molecular events controlling the HCMV replicative cycle. Here
      we identify a positive role for the MIE 5' UTR in mediating the efficient
      translation of the IE1 and IE2 mRNAs. This result is an important advance for
      several reasons. To date, most studies of IE1 and IE2 regulation have focused on
      defining events that regulate IE1 and IE2 transcription. Our work reveals that in
      addition to the regulation of transcription, IE1 and IE2 are also regulated at
      the level of translation. Therefore, this study is important in that it
      identifies an additional layer of regulation controlling IE1 and IE2 expression
      and thus HCMV pathogenesis. These translational regulatory events could
      potentially be targeted by novel antiviral therapeutics that limit IE1 and IE2
      mRNA translation and thus inhibit lytic replication or prevent HCMV reactivation.

PMID- 29343582
TI  - HIV Replication and Latency in a Humanized NSG Mouse Model during Suppressive
      Oral Combinational Antiretroviral Therapy.
AB  - Although current combinatorial antiretroviral therapy (cART) is therapeutically
      effective in the majority of HIV patients, interruption of therapy can cause a
      rapid rebound in viremia, demonstrating the existence of a stable reservoir of
      latently infected cells. HIV latency is therefore considered a primary barrier to
      HIV eradication. Identifying, quantifying, and purging the HIV reservoir is
      crucial to effectively curing patients and relieving them from the lifelong
      requirement for therapy. Latently infected transformed cell models have been used
      to investigate HIV latency; however, these models cannot accurately represent the
      quiescent cellular environment of primary latently infected cells in vivo For
      this reason, in vivo humanized murine models have been developed for screening
      antiviral agents, identifying latently infected T cells, and establishing
      treatment approaches for HIV research. Such models include humanized bone
      marrow/liver/thymus mice and SCID-hu-thy/liv mice, which are repopulated with
      human immune cells and implanted human tissues through laborious surgical
      manipulation. However, no one has utilized the human hematopoietic stem cell
      engrafted NOD/SCID/IL2rgammanull (NSG) model (hu-NSG) for this purpose.
      Therefore, in the present study, we used the HIV-infected hu-NSG mouse to
      recapitulate the key aspects of HIV infection and pathogenesis in vivo Moreover,
      we evaluated the ability of HIV-infected human cells isolated from HIV-infected
      hu-NSG mice on suppressive cART to act as a latent HIV reservoir. Our results
      demonstrate that the hu-NSG model is an effective surgery-free in vivo system in
      which to efficiently evaluate HIV replication, antiretroviral therapy, latency
      and persistence, and eradication interventions.IMPORTANCE HIV can establish a
      stably integrated, nonproductive state of infection at the level of individual
      cells, known as HIV latency, which is considered a primary barrier to curing HIV.
      A complete understanding of the establishment and role of HIV latency in vivo
      would greatly enhance attempts to develop novel HIV purging strategies. An ideal
      animal model for this purpose should be easy to work with, should have a
      shortened disease course so that efficacy testing can be completed in a
      reasonable time, and should have immune correlates that are easily translatable
      to humans. We therefore describe a novel application of the hematopoietic stem
      cell-transplanted humanized NSG model for dynamically testing antiretroviral
      treatment, supporting HIV infection, establishing HIV latency in vivo The hu-NSG
      model could be a facile alternative to humanized bone marrow/liver/thymus or SCID
      hu-thy/liv mice in which laborious surgical manipulation and time-consuming human
      cell reconstitution is required.

PMID- 29343583
TI  - Structural Study of the C-Terminal Domain of Nonstructural Protein 1 from
      Japanese Encephalitis Virus.
AB  - Japanese encephalitis virus (JEV) is a mosquito-transmitted flavivirus that is
      closely related to other emerging viral pathogens, including dengue virus (DENV),
      West Nile virus (WNV), and Zika virus (ZIKV). JEV infection can result in
      meningitis and encephalitis, which in severe cases cause permanent brain damage
      and death. JEV occurs predominantly in rural areas throughout Southeast Asia, the
      Pacific Islands, and the Far East, causing around 68,000 cases of infection
      worldwide each year. In this report, we present a 2.1-A-resolution crystal
      structure of the C-terminal beta-ladder domain of JEV nonstructural protein 1
      (NS1-C). The surface charge distribution of JEV NS1-C is similar to those of WNV
      and ZIKV but differs from that of DENV. Analysis of the JEV NS1-C structure, with
      in silico molecular dynamics simulation and experimental solution small-angle X
      ray scattering, indicates extensive loop flexibility on the exterior of the
      protein. This, together with the surface charge distribution, indicates that
      flexibility influences the protein-protein interactions that govern
      pathogenicity. These factors also affect the interaction of NS1 with the 22NS1
      monoclonal antibody, which is protective against West Nile virus infection.
      Liposome and heparin binding assays indicate that only the N-terminal region of
      NS1 mediates interaction with membranes and that sulfate binding sites common to
      NS1 structures are not glycosaminoglycan binding interfaces. This report
      highlights several differences between flavivirus NS1 proteins and contributes to
      our understanding of their structure-pathogenic function relationships.IMPORTANCE
      JEV is a major cause of viral encephalitis in Asia. Despite extensive
      vaccination, epidemics still occur. Nonstructural protein 1 (NS1) plays a role in
      viral replication, and, because it is secreted, it can exhibit a wide range of
      interactions with host proteins. NS1 sequence and protein folds are conserved
      within the Flavivirus genus, but variations in NS1 protein-protein interactions
      among viruses likely contribute to differences in pathogenesis. Here, we compared
      characteristics of the C-terminal beta-ladder domain of NS1 between flaviviruses,
      including surface charge, loop flexibility, epitope cross-reactivity, membrane
      adherence, and glycosaminoglycan binding. These structural features are central
      to NS1 functionality and may provide insight into the development of diagnostic
      tests and therapeutics.

PMID- 29343585
TI  - Rhinovirus in Febrile Infants and Risk of Bacterial Infection.
AB  - BACKGROUND: Febrile infants with viral respiratory infections have a reduced risk
      of bacterial infection compared with virus-negative infants. The risk of
      concomitant bacterial infection in febrile infants positive for human rhinovirus
      (HRV) by polymerase chain reaction (PCR) is unknown. METHODS: Infants 1-90 days
      old managed using the care process model for well-appearing febrile infants and
      with respiratory viral testing by PCR (RVPCR) in the emergency department or
      inpatient setting of 22 hospitals in the Intermountain Healthcare system from
      2007-2016 were identified. Relative risk (RR) of bacterial infection was
      calculated for infants with HRV, non-HRV viruses, or no virus detected. RESULTS:
      Of 10 964 febrile infants identified, 4037 (37%) had RVPCR. Of these, 2212 (55%)
      were positive for a respiratory virus; 1392 (35%) for HRV alone. Bacterial
      infection was identified in 9.5%. Febrile infants with HRV detected were more
      likely to have bacterial infection than those with non-HRV viruses (7.8% vs 3.7%;
      P < .001; RR 2.12 [95% CI 1.43-3.15]). Risk of urinary tract infection was not
      significantly different for HRV-positive infants at any age, nor was risk of
      invasive bacterial infection (IBI; bacteremia and/or meningitis) meaningfully
      different for infants 1-28 day olds. Infants 29-90 days old with HRV had a
      decreased likelihood of IBI (RR 0.52 [95% CI 0.34-0.80]). CONCLUSIONS: HRV is
      common in febrile infants. Detection did not alter risk of concomitant urinary
      tract infection at any age or risk of IBI in infants 1-28 days old. HRV detection
      may be relevant in considering risk of IBI for infants 29-90 days of age.

PMID- 29343586
TI  - A Case of Cardiomyopathy Due to Premature Ductus Arteriosus Closure: The Flip
      Side of Paracetamol.
AB  - Paracetamol (acetaminophen or N-acetyl-p-aminophenol) is considered a safe
      analgesic and antipyretic nonsteroidal antiinflammatory drug commonly used during
      pediatric ages and during pregnancy. We report on a term neonate with closed
      ductus arteriosus, severe cardiomyopathy, right ventricular dysfunction, and
      functional stenosis of pulmonary arteries at birth after maternal self-medication
      with paracetamol and consumption of polyphenol-rich foods in late pregnancy. This
      drug, especially when associated with other vasoconstrictors (such as
      polyphenols), interferes with prostaglandin metabolism, which seriously
      accentuates the intrauterine ductus arteriosus constriction and leads to
      pharmacologic adverse events. We suggest maternal educational programs to avoid
      risky self-medications and provide training for the best diets.

PMID- 29343584
TI  - Human Herpesvirus 8 Interferon Regulatory Factors 1 and 3 Mediate Replication and
      Latency Activities via Interactions with USP7 Deubiquitinase.
AB  - Human herpesvirus 8 (HHV-8) encodes four viral interferon regulatory factors
      (vIRF-1 to -4) that likely function to suppress innate immune and cellular stress
      responses through inhibitory interactions with various cellular proteins involved
      in these activities. It is notable that vIRF-1 and -4 have been reported to
      interact with the deubiquitinase ubiquitin-specific protease 7 (USP7), substrates
      of which include p53 and the p53-targeting and -destabilizing ubiquitin E3 ligase
      MDM2. Structural studies of vIRF-1 and vIRF-4 USP7 binding sequences in
      association with USP7 have been reported; both involve interactions with N
      terminal-domain residues of USP7 via EGPS and ASTS motifs in vIRF-1 and vIRF-4,
      respectively, but vIRF-4 residues also contact the catalytic site. However, the
      biological activities of vIRF-1 and vIRF-4 via USP7 interactions are unknown.
      Here, we report that vIRF-3, which is latently, as well as lytically, expressed
      in HHV-8-infected primary effusion lymphoma (PEL) cells, also interacts with USP7
      via duplicated EGPS motifs-and that this interaction is important for PEL cell
      growth and viability. The interaction also contributes to suppression of
      productive virus replication by vIRF-3, which we identify here. We further show
      that vIRF-1, which is expressed at low levels in PEL latency, promotes latent PEL
      cell viability and that this activity and vIRF-1-promoted productive replication
      (reported previously) involve EGPS motif-mediated USP7 targeting by vIRF-1. This
      study is the first to identify latent and lytic functions of vIRF-1 and vIRF-3,
      respectively, and to address the biological activities of these vIRFs through
      their interactions with USP7.IMPORTANCE HHV-8 is associated with Kaposi's
      sarcoma, primary effusion lymphoma (PEL), and multicentric Castleman's disease;
      both latent and lytic viral functions are believed to contribute. Viral
      interferon regulatory factors specified by HHV-8 are thought to be critically
      important for successful productive replication through suppression of innate
      immune and stress responses triggered by the lytic cycle. Latently expressed vIRF
      3 contributes significantly to PEL cell survival. Here, we identify ubiquitin
      specific protease 7 (USP7) deubiquitinase targeting by vIRF-3 (in addition to
      previously reported USP7 binding by vIRF-1 and vIRF-4); the importance of vIRF-1
      and vIRF-3 interactions with USP7 for latent PEL cell growth and viability; and
      the positive and negative contributions, respectively, of USP7 targeting by vIRF
      1 and vIRF-3 to HHV-8 productive replication. This is the first report of the
      biological importance of vIRF-1 in PEL cell latency, the modulation of productive
      replication by vIRF-3, and the contributions of vIRF-USP7 interactions to HHV-8
      biology.

PMID- 29343587
TI  - Surgical Management of Moyamoya Disease.

PMID- 29343589
TI  - Dramatic extremity temperature increase and Horner's syndrome after stellate
      ganglion block.

PMID- 29343590
TI  - New Reviewer Mentoring Program.

PMID- 29343588
TI  - Modeling the Impact of Interhospital Transfer Network Design on Stroke Outcomes
      in a Large City.
AB  - BACKGROUND AND PURPOSE: We sought to model the effects of interhospital transfer
      network design on endovascular therapy eligibility and clinical outcomes of
      stroke because of large-vessel occlusion for the residents of a large city.
      METHODS: We modeled 3 transfer network designs for New York City. In model A,
      patients were transferred from spoke hospitals to the closest hub hospitals with
      endovascular capabilities irrespective of hospital affiliation. In model B, which
      was considered the base case, patients were transferred to the closest affiliated
      hub hospitals. In model C, patients were transferred to the closest affiliated
      hospitals, and transfer times were adjusted to reflect full implementation of
      streamlined transfer protocols. Using Monte Carlo methods, we simulated the
      distributions of endovascular therapy eligibility and good functional outcomes
      (modified Rankin Scale score, 0-2) in these models. RESULTS: In our models, 200
      patients (interquartile range [IQR], 168-227) with a stroke amenable to
      endovascular therapy present to New York City spoke hospitals each year.
      Transferring patients to the closest hub hospital irrespective of affiliation
      (model A) resulted in 4 (IQR, 1-9) additional patients being eligible for
      endovascular therapy and an additional 1 (IQR, 0-2) patient achieving functional
      independence. Transferring patients only to affiliated hospitals while simulating
      full implementation of streamlined transfer protocols (model C) resulted in 17
      (IQR, 3-41) additional patients being eligible for endovascular therapy and 3
      (IQR, 1-8) additional patients achieving functional independence. CONCLUSIONS:
      Optimizing acute stroke transfer networks resulted in clinically small changes in
      population-level stroke outcomes in a dense, urban area.

PMID- 29343591
TI  - Sleep-Stage-Dependent Hippocampal Coordination with Cingulate and Retrosplenial
      Association Cortices.

PMID- 29343592
TI  - New Insights on the Role of Residue 673 of APP in Alzheimer's Disease.

PMID- 29343593
TI  - Lizards of the lost arcs: mid-Cenozoic diversification, persistence and
      ecological marginalization in the West Pacific.
AB  - Regions with complex geological histories often have diverse and highly endemic
      biotas, yet inferring the ecological and historical processes shaping this
      relationship remains challenging. Here, in the context of the taxon cycle model
      of insular community assembly, we investigate patterns of lineage diversity and
      habitat usage in a newly characterized vertebrate radiation centred upon the
      world's most geologically complex insular region: island arcs spanning from the
      Philippines to Fiji. On island arcs taxa are ecologically widespread, and provide
      evidence to support one key prediction of the taxon cycle, specifically that
      interior habitats (lowland rainforests, montane habitats) are home to a greater
      number of older or relictual lineages than are peripheral habitats (coastal and
      open forests). On continental fringes, however, the clade shows a disjunct
      distribution away from lowland rainforest, occurring in coastal, open or montane
      habitats. These results are consistent with a role for biotic interactions in
      shaping disjunct distributions (a central tenant of the taxon cycle), but we find
      this pattern most strongly on continental fringes not islands. Our results also
      suggest that peripheral habitats on islands, and especially island arcs, may be
      important for persistence and diversification, not just dispersal and
      colonization. Finally, new phylogenetic evidence for subaerial island
      archipelagos (with an associated biota) east of present-day Wallace's Line since
      the Oligocene has important implications for understanding long-term biotic
      interchange and assembly across Asia and Australia.

PMID- 29343594
TI  - Strong social relationships are associated with decreased longevity in a
      facultatively social mammal.
AB  - Humans in strong social relationships are more likely to live longer because
      social relationships may buffer stressors and thus have protective effects.
      However, a shortcoming of human studies is that they often rely on self-reporting
      of these relationships. By contrast, observational studies of non-human animals
      permit detailed analyses of the specific nature of social relationships. Thus,
      discoveries that some social animals live longer and healthier lives if they are
      involved in social grooming, forage together or have more affiliative associates
      emphasizes the potential importance of social relationships on health and
      longevity. Previous studies have focused on the impact of social metrics on
      longevity in obligately social species. However, if sociality indeed has a key
      role in longevity, we might expect that affiliative relationships should also
      influence longevity in less social species. We focused on socially flexible
      yellow-bellied marmots (Marmota flaviventer) and asked whether female longevity
      covaries with the specific nature of social relationships. We quantified social
      relationships with social network statistics that were based on affiliative
      interactions, and then estimated the correlation between longevity and sociality
      using bivariate models. We found a significant negative phenotypic correlation
      between affiliative social relationship strength and longevity; marmots with
      greater degree, closeness and those with a greater negative average shortest path
      length died at younger ages. We conclude that sociality plays an important role
      in longevity, but how it does so may depend on whether a species is obligately or
      facultatively social.

PMID- 29343595
TI  - Balanced genetic diversity improves population fitness.
AB  - Although genetic diversity within a population is suggested to improve population
      level fitness and productivity, the existence of these effects is controversial
      because empirical evidence for an ecological effect of genetic diversity and the
      underlying mechanisms is scarce and incomplete. Here, we show that the natural
      single-gene behavioural polymorphism (Rover and sitter) in Drosophila
      melanogaster has a positive effect on population fitness. Our simple numerical
      model predicted that the fitness of a polymorphic population would be higher than
      that expected with two monomorphic populations, but only under balancing
      selection. Moreover, this positive diversity effect of genetic polymorphism was
      attributable to a complementarity effect, rather than to a selection effect. Our
      empirical tests using the behavioural polymorphism in D. melanogaster clearly
      supported the model predictions. These results provide direct evidence for an
      ecological effect of genetic diversity on population fitness and its condition
      dependence.

PMID- 29343596
TI  - Daphnia invest in sexual reproduction when its relative costs are reduced.
AB  - The timing of sex in facultatively sexual organisms is critical to fitness, due
      to the differing demographic consequences of sexual versus asexual reproduction.
      In addition to the costs of sex itself, an association of sex with the production
      of dormant life stages also influences the optimal use of sex, especially in
      environments where resting eggs are essential to survive unfavourable conditions.
      Here we document population dynamics and the occurrence of sexual reproduction in
      natural populations of Daphnia magna across their growing season. The frequency
      of sexually reproducing females and males increased with population density and
      with decreasing asexual clutch sizes. The frequency of sexually reproducing
      females additionally increased as population growth rates decreased. Consistent
      with population dynamic models showing that the opportunity cost of sexual
      reproduction (foregoing contribution to current population growth) diminishes as
      populations approach carrying capacity, we found that investment in sexual
      reproduction was highest when asexual population growth was low or negative. Our
      results support the idea that the timing of sex is linked with periods when the
      relative cost of sex is reduced due to low potential asexual growth at high
      population densities. Thus, a combination of ecological and demographic factors
      affect the optimal timing of sexual reproduction, allowing D. magna to balance
      the necessity of sex against its costs.

PMID- 29343597
TI  - Evidence for dispersal syndromes in freshwater fishes.
AB  - Dispersal is a fundamental process defining the distribution of organisms and has
      long been a topic of inquiry in ecology and evolution. Emerging research points
      to an interdependency of dispersal with a diverse suite of traits in terrestrial
      organisms, however the extent to which such dispersal syndromes exist in
      freshwater species remains uncertain. Here, we test whether dispersal in
      freshwater fishes (1) is a fixed property of species, and (2) correlates with
      life-history, morphological, ecological and behavioural traits, using a global
      dataset of dispersal distances collected from the literature encompassing 116
      riverine species and 196 locations. Our meta-analysis revealed a high degree of
      repeatability and heritability in the dispersal estimates and strong associations
      with traits related to life-history strategies, energy allocation to
      reproduction, ecological specialization and swimming skills. Together, these
      results demonstrate that similar to terrestrial organisms, the multi-dimensional
      nature of dispersal syndromes in freshwater species offer opportunities for the
      development of a unifying paradigm of movement ecology that transcend taxonomic
      and biogeographical realms. The high explanatory power of the models also
      suggests that trait-based and phylogenetic approaches hold considerable promises
      to inform conservation efforts in a rapidly changing world.

PMID- 29343598
TI  - Coadaptation of mitochondrial and nuclear genes, and the cost of mother's curse.
AB  - Strict maternal inheritance renders the mitochondrial genome susceptible to
      accumulating mutations that harm males, but are otherwise benign or beneficial
      for females. This 'mother's curse' effect can degrade male survival and fertility
      if unopposed by counteracting evolutionary processes. Coadaptation between
      nuclear and mitochondrial genomes-with nuclear genes evolving to compensate for
      male-harming mitochondrial substitutions-may ultimately resolve mother's curse.
      However, males are still expected to incur a transient fitness cost during mito
      nuclear coevolution, and it remains unclear how severe such costs should be. We
      present a population genetic analysis of mito-nuclear coadaptation to resolve
      mother's curse effects, and show that the magnitude of the 'male mitochondrial
      load'-the negative impact of mitochondrial substitutions on male fitness
      components-may be large, even when genetic variation for compensatory evolution
      is abundant. We also find that the male load is surprisingly sensitive to
      population size: male fitness costs of mito-nuclear coevolution are particularly
      pronounced in both small and large populations, and minimized in populations of
      intermediate size. Our results reveal complex interactions between demography and
      genetic constraints during the resolution of mother's curse, suggesting
      potentially widespread species differences in susceptibility to mother's curse
      effects.

PMID- 29343599
TI  - The evolution of tail weaponization in amniotes.
AB  - Weaponry, for the purpose of intraspecific combat or predator defence, is one of
      the most widespread animal adaptations, yet the selective pressures and
      constraints governing its phenotypic diversity and skeletal regionalization are
      not well understood. Here, we investigate the evolution of tail weaponry in
      amniotes, a rare form of weaponry that nonetheless evolved independently among a
      broad spectrum of life including mammals, turtles and dinosaurs. Using
      phylogenetic comparative methods, we test for links between morphology, ecology
      and behaviour in extant amniotes known to use the tail as a weapon, and in
      extinct taxa bearing osseous tail armaments. We find robust ecological and
      morphological correlates of both tail lashing behaviour and bony tail weaponry,
      including large body size, body armour and herbivory, suggesting these life
      history parameters factor into the evolution of antipredator behaviours and tail
      armaments. We suggest that the evolution of tail weaponry is rare because large,
      armoured herbivores are uncommon in extant terrestrial faunas, as they have been
      throughout evolutionary history.

PMID- 29343600
TI  - Rapid phenotypic evolution following shifts in life cycle complexity.
AB  - Life cycle strategies have evolved extensively throughout the history of
      metazoans. The expression of disparate life stages within a single ontogeny can
      present conflicts to trait evolution, and therefore may have played a major role
      in shaping metazoan forms. However, few studies have examined the consequences of
      adding or subtracting life stages on patterns of trait evolution. By analysing
      trait evolution in a clade of closely related salamander lineages we show that
      shifts in the number of life cycle stages are associated with rapid phenotypic
      evolution. Specifically, salamanders with an aquatic-only (paedomorphic) life
      cycle have frequently added vertebrae to their trunk skeleton compared with
      closely related lineages with a complex aquatic-to-terrestrial (biphasic) life
      cycle. The rate of vertebral column evolution is also substantially lower in
      biphasic lineages, which may reflect the functional compromise of a complex
      cycle. This study demonstrates that the consequences of life cycle evolution can
      be detected at very fine scales of divergence. Rapid evolutionary responses can
      result from shifts in selective regimes following changes in life cycle
      complexity.

PMID- 29343601
TI  - The evolution of sexual signal modes and associated sensor morphology in
      fireflies (Lampyridae, Coleoptera).
AB  - Animals employ different sexual signal modes (e.g. visual, acoustic, chemical) in
      different environments and behavioural contexts. If sensory structures are
      costly, then evolutionary shifts in primary signal mode should be associated with
      changes in sensor morphology. Further, sex differences are expected if male and
      female signalling behaviours differ. Fireflies are known for their light
      displays, but many species communicate exclusively with pheromones, including
      species that recently lost their light signals. We performed phylogenetically
      controlled analyses of male eye and antenna size in 46 North American taxa, and
      found that light signals are associated with larger eyes and shorter antennae. In
      addition, following a transition from nocturnal light displays to diurnal
      pheromones, eye size reductions occur more rapidly than antenna size increases.
      In agreement with the North American taxa, across 101 worldwide firefly taxa in
      32 genera, we found light displays are associated with larger eye and smaller
      antenna sizes in both males and females. For those taxa with both male and female
      data, we found sex differences in eye size and, for diurnal species, in antenna
      size.

PMID- 29343602
TI  - Bayesian inference reveals positive but subtle effects of experimental fishery
      closures on marine predator demographics.
AB  - Global forage-fish landings are increasing, with potentially grave consequences
      for marine ecosystems. Predators of forage fish may be influenced by this
      harvest, but the nature of these effects is contentious. Experimental fishery
      manipulations offer the best solution to quantify population-level impacts, but
      are rare. We used Bayesian inference to examine changes in chick survival, body
      condition and population growth rate of endangered African penguins Spheniscus
      demersus in response to 8 years of alternating time-area closures around two
      pairs of colonies. Our results demonstrate that fishing closures improved chick
      survival and condition, after controlling for changing prey availability.
      However, this effect was inconsistent across sites and years, highlighting the
      difficultly of assessing management interventions in marine ecosystems.
      Nevertheless, modelled increases in population growth rates exceeded 1% at one
      colony; i.e. the threshold considered biologically meaningful by fisheries
      management in South Africa. Fishing closures evidently can improve the population
      trend of a forage-fish-dependent predator-we therefore recommend they continue in
      South Africa and support their application elsewhere. However, detecting
      demographic gains for mobile marine predators from small no-take zones requires
      experimental time frames and scales that will often exceed those desired by
      decision makers.

PMID- 29343603
TI  - Mutual assessment during ritualized fighting in mantis shrimp (Stomatopoda).
AB  - Safe and effective conflict resolution is critical for survival and reproduction.
      Theoretical models describe how animals resolve conflict by assessing their own
      and/or their opponent's ability (resource holding potential, RHP), yet
      experimental tests of these models are often inconclusive. Recent reviews have
      suggested this uncertainty could be alleviated by using multiple approaches to
      test assessment models. The mantis shrimp Neogonodactylus bredini presents visual
      displays and ritualistically exchanges high-force strikes during territorial
      contests. We tested how N. bredini contest dynamics were explained by any of
      three assessment models-pure self-assessment, cumulative assessment and mutual
      assessment-using correlations and a novel, network analysis-based sequential
      behavioural analysis. We staged dyadic contests over burrow access between
      competitors matched either randomly or based on body size. In both randomly and
      size-matched contests, the best metric of RHP was body mass. Burrow residency
      interacted with mass to predict outcome. Correlations between contest costs and
      RHP rejected pure self-assessment, but could not fully differentiate between
      cumulative and mutual assessment. The sequential behavioural analysis ruled out
      cumulative assessment and supported mutual assessment. Our results demonstrate
      how multiple analyses provide strong inference to tests of assessment models and
      illuminate how individual behaviours constitute an assessment strategy.

PMID- 29343604
TI  - Urbanization and anticoagulant poisons promote immune dysfunction in bobcats.
AB  - Understanding how human activities influence immune response to environmental
      stressors can support biodiversity conservation across increasingly urbanizing
      landscapes. We studied a bobcat (Lynx rufus) population in urban southern
      California that experienced a rapid population decline from 2002-2005 due to
      notoedric mange. Because anticoagulant rodenticide (AR) exposure was an
      underlying complication in mange deaths, we aimed to understand sublethal
      contributions of urbanization and ARs on 65 biochemical markers of immune and
      organ function. Variance in immunological variables was primarily associated with
      AR exposure and secondarily with urbanization. Use of urban habitat and AR
      exposure has pervasive, complex and predictable effects on biochemical markers of
      immune and organ function in free-ranging bobcats that include impacts on
      neutrophil, lymphocyte and cytokine populations, total bilirubin and phosphorus.
      We find evidence of both inflammatory response and immune suppression associated
      with urban land use and rat poison exposure that could influence susceptibility
      to opportunistic infections. Consequently, AR exposure may influence mortality
      and has population-level effects, as previous work in the focal population has
      revealed substantial mortality caused by mange infection. The secondary effects
      of anticoagulant exposure may be a worldwide, largely unrecognized problem
      affecting a variety of vertebrate species in human-dominated environments.

PMID- 29343605
TI  - Experimental heatwaves negatively impact sperm quality in the zebra finch.
AB  - For sexually reproducing species, functionally competent sperm are critical to
      reproduction. While high atmospheric temperatures are known to influence the
      timing of breeding, incubation and reproductive success in birds, the effect of
      temperature on sperm quality remains largely unexplored. Here, we experimentally
      investigated the impact of ecologically relevant extreme temperatures on cloacal
      temperature and sperm morphology and motility in zebra finches Taeniopygia
      guttata We periodically sampled males exposed to 30 degrees C or 40 degrees C
      temperatures daily for 14 consecutive days. Following a 12-day (23 degrees C)
      recovery period, birds were again exposed to heat, but under the alternate
      treatment (e.g. birds initially exposed to 40 degrees C were exposed to 30
      degrees C). Elevated temperatures led to an increase in cloacal temperature and a
      reduction in the proportion of sperm with normal morphology; these effects were
      most notable under 40 degrees C conditions, and were influenced by the duration
      of heat exposure and prior exposure to high temperature. Our findings highlight
      the potential role of temperature in determining male fertility in birds, and
      perhaps also in constraining the timing of avian breeding. Given the increased
      frequency of heatwaves in a warming world, our results suggest the need for
      further work on climatic influences on sperm quality and male fertility.

PMID- 29343606
TI  - Correction to 'Species identity and depth predict bleaching severity in reef
      building corals: shall the deep inherit the reef'.

PMID- 29343607
TI  - Behavioural tactic predicts preoptic-hypothalamic gene expression more strongly
      than developmental morph in fish with alternative reproductive tactics.
AB  - Reproductive success relies on the coordination of social behaviours, such as
      territory defence, courtship and mating. Species with extreme variation in
      reproductive tactics are useful models for identifying the neural mechanisms
      underlying social behaviour plasticity. The plainfin midshipman (Porichthys
      notatus) is a teleost fish with two male reproductive morphs that follow widely
      divergent developmental trajectories and display alternative reproductive tactics
      (ARTs). Type I males defend territories, court females and provide paternal care,
      but will resort to cuckoldry if they cannot maintain a territory. Type II males
      reproduce only through cuckoldry. We sought to disentangle gene expression
      patterns underlying behavioural tactic, in this case ARTs, from those solely
      reflective of developmental morph. Using RNA-sequencing, we investigated
      differential transcript expression in the preoptic area-anterior hypothalamus
      (POA-AH) of courting type I males, cuckolding type I males and cuckolding type II
      males. Unexpectedly, POA-AH differential expression was more strongly coupled to
      behavioural tactic than morph. This included a suite of transcripts implicated in
      hormonal regulation of vertebrate social behaviour. Our results reveal that
      divergent expression patterns in a conserved neuroendocrine centre known to
      regulate social-reproductive behaviours across vertebrate lineages may be
      uncoupled from developmental history to enable plasticity in the performance of
      reproductive tactics.

PMID- 29343608
TI  - Direct Quantification of Cytochromes P450 and Drug Transporters-A Rapid, Targeted
      Mass Spectrometry-Based Immunoassay Panel for Tissues and Cell Culture Lysates.
AB  - The quantification of drug metabolizing enzymes and transporters has recently
      been revolutionized on the basis of targeted proteomic approaches. Isotope
      labeled peptides are used as standards for the quantification of the
      corresponding proteins in enzymatically fragmented samples. However, hurdles in
      these approaches are low throughput and tedious sample prefractionation steps
      prior to mass spectrometry (MS) readout. We have developed an assay platform
      using sensitive and selective immunoprecipitation coupled with mass spectrometric
      readout allowing the quantification of proteins directly from whole cell lysates
      using less than 20,000 cells per analysis. Peptide group-specific antibodies
      (triple X proteomics antibodies) enable the enrichment of proteotypic peptides
      sharing a common terminus. These antibodies were employed to establish a MS-based
      immunoassay panel for the quantification of 14 cytochrome P450 (P450) enzymes and
      nine transporters. We analyzed the P450 enzyme and transporter levels in
      genotyped liver tissue homogenates and microsomes, and in samples from a time
      course induction experiment in human hepatocytes addressing different induction
      pathways. For the analysis of P450 enzymes and transporters only a minute amount
      of sample is required and no prefractionation is necessary, thus the assay
      platform bears the potential to bridge cell culture model experiments and results
      from whole organ tissue studies.

PMID- 29343609
TI  - Polymorphic Human Sulfotransferase 2A1 Mediates the Formation of 25
      Hydroxyvitamin D3-3-O-Sulfate, a Major Circulating Vitamin D Metabolite in
      Humans.
AB  - Metabolism of 25-hydroxyvitamin D3 (25OHD3) plays a central role in regulating
      the biologic effects of vitamin D in the body. Although cytochrome P450-dependent
      hydroxylation of 25OHD3 has been extensively investigated, limited information is
      available on the conjugation of 25OHD3 In this study, we report that 25OHD3 is
      selectively conjugated to 25OHD3-3-O-sulfate by human sulfotransferase 2A1
      (SULT2A1) and that the liver is a primary site of metabolite formation. At a low
      (50 nM) concentration of 25OHD3, 25OHD3-3-O-sulfate was the most abundant
      metabolite, with an intrinsic clearance approximately 8-fold higher than the next
      most efficient metabolic route. In addition, 25OHD3 sulfonation was not inducible
      by the potent human pregnane X receptor agonist, rifampicin. The 25OHD3
      sulfonation rates in a bank of 258 different human liver cytosols were highly
      variable but correlated with the rates of dehydroepiandrosterone sulfonation.
      Further analysis revealed a significant association between a common single
      nucleotide variant within intron 1 of SULT2A1 (rs296361; minor allele frequency =
      15% in whites) and liver cytosolic SULT2A1 content as well as 25OHD3-3-O-sulfate
      formation rate, suggesting that variation in the SULT2A1 gene contributes
      importantly to interindividual differences in vitamin D homeostasis. Finally,
      25OHD3-3-O-sulfate exhibited high affinity for the vitamin D binding protein and
      was detectable in human plasma and bile but not in urine samples. Thus,
      circulating concentrations of 25OHD3-3-O-sulfate appear to be protected from
      rapid renal elimination, raising the possibility that the sulfate metabolite may
      serve as a reservoir of 25OHD3 in vivo, and contribute indirectly to the biologic
      effects of vitamin D.

PMID- 29343611
TI  - Structural insights into the catalytic mechanism of cysteine (hydroxyl) lyase
      from the hydrogen sulfide-producing oral pathogen, Fusobacterium nucleatum.
AB  - Hydrogen sulfide (H2S) plays important roles in the pathogenesis of
      periodontitis. Oral pathogens typically produce H2S from l-cysteine in addition
      to pyruvate and [Formula: see text] However, fn1055 from Fusobacterium nucleatum
      subsp. nucleatum ATCC 25586 encodes a pyridoxal 5'-phosphate (PLP)-dependent
      enzyme that catalyzes the production of H2S and l-serine from l-cysteine and H2O,
      an unusual cysteine (hydroxyl) lyase reaction (beta-replacement reaction). To
      reveal the reaction mechanism, the crystal structure of substrate-free Fn1055 was
      determined. Based on this structure, a model of the l-cysteine-PLP Schiff base
      suggested that the thiol group forms hydrogen bonds with Asp232 and Ser74, and
      the substrate alpha-carboxylate interacts with Thr73 and Gln147 Asp232 is a
      unique residue to Fn1055 and its substitution to asparagine (D232N) resulted in
      almost complete loss of beta-replacement activity. The D232N structure obtained
      in the presence of l-cysteine contained the alpha-aminoacrylate-PLP Schiff base
      in the active site, indicating that Asp232 is essential for the addition of water
      to the alpha-aminoacrylate to produce the l-serine-PLP Schiff base. Rapid-scan
      stopped-flow kinetic analyses showed an accumulation of the alpha-aminoacrylate
      intermediate during the reaction cycle, suggesting that water addition mediated
      by Asp232 is the rate-limiting step. In contrast, mutants containing
      substitutions of other active-site residues (Ser74, Thr73, and Gln147) exhibited
      reduced beta-replacement activity by more than 100-fold. Finally, based on the
      structural and biochemical analyses, we propose a mechanism of the cysteine
      (hydroxyl) lyase reaction by Fn1055. The present study leads to elucidation of
      the H2S-producing mechanism in F. nucleatum.

PMID- 29343610
TI  - CYP2J2 Expression in Adult Ventricular Myocytes Protects Against Reactive Oxygen
      Species Toxicity.
AB  - Cytochrome P450 2J2 isoform (CYP2J2) is a drug-metabolizing enzyme that is highly
      expressed in adult ventricular myocytes. It is responsible for the bioactivation
      of arachidonic acid (AA) into epoxyeicosatrienoic acids (EETs). EETs are
      biologically active signaling compounds that protect against disease progression,
      particularly in cardiovascular diseases. As a drug-metabolizing enzyme, CYP2J2 is
      susceptible to drug interactions that could lead to cardiotoxicity. CYP2J2 has
      been shown to be resistant to induction by canonical CYP inducers such as
      phenytoin and rifampin. It is, however, unknown how cellular stresses augment
      CYP2J2 expression. Here, we determine the effects of oxidative stress on gene
      expression in adult ventricular myocytes. Further, we assess the consequences of
      CYP2J2 inhibition and CYP2J2 silencing on cells when levels of reactive oxygen
      species (ROS) are elevated. Findings indicate that CYP2J2 expression increases in
      response to external ROS or when internal ROS levels are elevated. In addition,
      cell survival decreases with ROS exposure when CYP2J2 is chemically inhibited or
      when CYP2J2 expression is reduced using small interfering RNA. These effects are
      mitigated with external addition of EETs to the cells. Finally, we determined the
      results of external EETs on gene expression and show that only two of the four
      regioisomers cause an increase in HMOX1 expression. This work is the first to
      determine the consequence of cellular stress, specifically high ROS levels, on
      CYP2J2 expression in human ventricular myocytes and discusses how this enzyme may
      play an important role in response to cardiac oxidative stress.

PMID- 29343612
TI  - Structural and functional characterisation of the cytochrome P450 enzyme CYP268A2
      from Mycobacterium marinum.
AB  - Members of the cytochrome P450 monooxygenase family CYP268 are found across a
      broad range of Mycobacterium species including the pathogens Mycobacterium avium,
      M. colombiense, M. kansasii, and Mmarinum CYP268A2, from M. marinum, which is the
      first member of this family to be studied, was purified and characterised.
      CYP268A2 was found to bind a variety of substrates with high affinity, including
      branched and straight chain fatty acids (C10-C12), acetate esters, and aromatic
      compounds. The enzyme was also found to bind phenylimidazole inhibitors but not
      larger azoles, such as ketoconazole. The monooxygenase activity of CYP268A2 was
      efficiently reconstituted using heterologous electron transfer partner proteins.
      CYP268A2 hydroxylated geranyl acetate and trans-pseudoionone at a terminal methyl
      group to yield (2E,6E)-8-hydroxy-3,7-dimethylocta-2,6-dien-1-yl acetate and
      (3E,5E,9E)-11-hydroxy-6,10-dimethylundeca-3,5,9-trien-2-one, respectively. The X
      ray crystal structure of CYP268A2 was solved to a resolution of 2.0 A with trans
      pseudoionone bound in the active site. The overall structure was similar to that
      of the related phytanic acid monooxygenase CYP124A1 enzyme from Mycobacterium
      tuberculosis, which shares 41% sequence identity. The active site is
      predominantly hydrophobic, but includes the Ser99 and Gln209 residues which form
      hydrogen bonds with the terminal carbonyl group of the pseudoionone. The
      structure provided an explanation on why CYP268A2 shows a preference for shorter
      substrates over the longer chain fatty acids which bind to CYP124A1 and the
      selective nature of the catalysed monooxygenase activity.

PMID- 29343613
TI  - Restricted HIV-1 Env glycan engagement by lectin-reengineered DAVEI protein
      chimera is sufficient for lytic inactivation of the virus.
AB  - We previously reported a first-generation recombinant DAVEI construct, a dual
      action virus entry inhibitor composed of cyanovirin-N (CVN) fused to a membrane
      proximal external region or its derivative peptide Trp3. DAVEI exhibits potent
      and irreversible inactivation of HIV-1 (human immunodeficiency virus) viruses by
      dual engagement of gp120 and gp41. However, the promiscuity of CVN to associate
      with multiple glycosylation sites in gp120 and its multivalency limit current
      understanding of the molecular arrangement of the DAVEI molecules on trimeric
      spike. Here, we constructed and investigated the virolytic function of second
      generation DAVEI molecules using a simpler lectin, microvirin (MVN). MVN is a
      monovalent lectin with a single glycan-binding site in gp120, is structurally
      similar to CVN and exhibits no toxicity or mitogenicity, both of which are
      liabilities with CVN. We found that, like CVN-DAVEI-L2-3Trp (peptide sequence
      DKWASLWNW), MVN-DAVEI2-3Trp exploits a similar mechanism of action for inducing
      HIV-1 lytic inactivation, but by more selective gp120 glycan engagement. By
      sequence redesign, we significantly increased the potency of MVN-DAVEI2-3Trp
      protein. Unlike CVN-DAVEI2-3Trp, re-engineered MVN-DAVEI2-3Trp(Q81K/M83R)
      virolytic activity and its interaction with gp120 were both competed by 2G12
      antibody. That the lectin domain in DAVEIs can utilize MVN without loss of
      virolytic function argues that restricted HIV-1 Env (envelope glycoprotein)
      glycan engagement is sufficient for virolysis. It also shows that DAVEI lectin
      multivalent binding with gp120 is not required for virolysis. MVN-DAVEI2
      3Trp(Q81K/M83R) provides an improved tool to elucidate productive molecular
      arrangements of Env-DAVEI enabling virolysis and also opens the way to form DAVEI
      fusions made up of gp120-binding small molecules linked to Trp3 peptide.

PMID- 29343615
TI  - Growth of human breast cancers in Peromyscus.
AB  - Modeling breast cancer in general and hormone-sensitive breast cancer, in
      particular in mice, has several limitations. These are related to the inbred
      nature of laboratory mice, and do not allow adequate appreciation of the
      contribution of the host's genetic heterogeneity in tumor growth. In addition,
      the naturally low estrogen levels of mice makes estradiol supplementation
      obligatory for tumor growth. Here, we show that Peromyscus californicus,
      following cyclosporine-mediated immunosuppression, supports the growth of both
      MDA-MB-231 estrogen-independent and MCF7 estrogen receptor-positive breast
      cancers without exogenous estradiol supplementation. Tumor growth was inhibited
      by fulvestrant or letrozole, confirming that MCF7 xenografts remain hormone
      dependent in vivo and suggesting that P. californicus can be used as an
      alternative to conventional mice for the study of hormone-sensitive breast
      cancer. The fact that Peromyscus stocks are outbred also facilitates the study of
      breast cancer in genetically heterogenous populations.

PMID- 29343616
TI  - Rapamycin activates TGF receptor independently of its ligand: implications for
      endothelial dysfunction.
AB  - Rapamycin, the macrolide immunosuppressant and active pharmaceutic in drug
      eluting stents (DES), has a well-recognized antiproliferative action that
      involves inhibition of the mTOR pathway after binding to the cytosolic protein
      FKBP12. TGF receptor-type I (TGFRI) spontaneous activation is inhibited by the
      association with FKBP12. We hypothesized that rapamycin, in addition to
      inhibition of mTOR signaling, activates TGFRI independent of TGFbeta. Human
      umbilical vein endothelial cells (HUVECs) were treated with rapamycin (10 nmol/l)
      and/or TGFbeta RI kinase inhibitor (TGFRIi, 100 nmol/l) for 24 h. Rapamycin
      induced SMAD phosphorylation (SMAD1, SMAD2, and SMAD5) and PAI-1 up-regulation,
      which was specifically abrogated by SMAD2 knockdown. TGFRIi efficiently blocked
      phosphorylation of SMAD2, but not SMAD1/5. Interestingly, the inhibitor did not
      alter cell proliferation arrest induced by rapamycin. Active TGFbeta secretion
      was not affected by the treatment. Neutralizing TGFbeta experiments did not
      influence SMAD2 phosphorylation or PAI-1 expression indicating that activation of
      this pathway is independent of the ligand. In addition, rapamycin induction of
      endothelial-to-mesenchymal transition (EndMT) was potentiated by IL-1beta and
      efficiently blocked by TGFRIi. In vivo, the prothrombogenic effects of rapamycin
      and up-regulation of PAI-1 in murine carotid arteries were reduced by TGFRIi
      treatment. In conclusion, we provide evidence that rapamycin activates TGF
      receptor independent of its ligand TGFbeta, in concert with promotion of PAI-1
      expression and changes in endothelial phenotype. These undesirable effects, the
      prothrombogenic state, and activation of EndMT are SMAD2-dependent and
      independent of the therapeutic rapamycin-induced cell proliferation arrest.

PMID- 29343614
TI  - Suppressor of cytokine signaling 2 (Socs2) deletion protects bone health of mice
      with DSS-induced inflammatory bowel disease.
AB  - Individuals with inflammatory bowel disease (IBD) often present with poor bone
      health. The development of targeted therapies for this bone loss requires a
      fuller understanding of the underlying cellular mechanisms. Although bone loss in
      IBD is multifactorial, the altered sensitivity and secretion of growth hormone
      (GH) and insulin-like growth factor-1 (IGF-1) in IBD is understood to be a
      critical contributing mechanism. The expression of suppressor of cytokine
      signaling 2 (SOCS2), a well-established negative regulator of GH signaling, is
      stimulated by proinflammatory cytokines. Therefore, it is likely that SOCS2
      expression represents a critical mediator through which proinflammatory cytokines
      inhibit GH/IGF-1 signaling and decrease bone quality in IBD. Using the dextran
      sodium sulfate (DSS) model of colitis, we reveal that endogenously elevated GH
      function in the Socs2-/- mouse protects the skeleton from osteopenia. Micro
      computed tomography assessment of DSS-treated wild-type (WT) mice revealed a
      worsened trabecular architecture compared to control mice. Specifically, DSS
      treated WT mice had significantly decreased bone volume, trabecular thickness and
      trabecular number, and a resulting increase in trabecular separation. In
      comparison, the trabecular bone of Socs2-deficient mice was partially protected
      from the adverse effects of DSS. The reduction in a number of parameters,
      including bone volume, was less, and no changes were observed in trabecular
      thickness or separation. This protected phenotype was unlikely to be a
      consequence of improved mucosal health in the DSS-treated Socs2-/- mice but
      rather a result of unregulated GH signaling directly on bone. These studies
      indicate that the absence of SOCS2 is protective against bone loss typical of
      IBD. This study also provides an improved understanding of the relative effects
      of GH/IGF-1 signaling on bone health in experimental colitis, information that is
      essential before these drugs are explored as bone protective agents in children
      and adults with IBD.

PMID- 29343617
TI  - Methods To Determine the Silicone Oil Layer Thickness in Sprayed-On Siliconized
      Syringes.
AB  - The silicone lubricant layer in prefilled syringes has been investigated with
      regards to siliconization process performance, prefilled syringe functionality,
      and drug product attributes, such as subvisible particle levels, in several
      studies in the past. However, adequate methods to characterize the silicone oil
      layer thickness and distribution are limited, and systematic evaluation is
      missing. In this study, white light interferometry was evaluated to close this
      gap in method understanding. White light interferometry demonstrated a good
      accuracy of 93-99% for MgF2 coated, curved standards covering a thickness range
      of 115-473 nm. Thickness measurements for sprayed-on siliconized prefilled
      syringes with different representative silicone oil distribution patterns
      (homogeneous, pronounced siliconization at flange or needle side, respectively)
      showed high instrument (0.5%) and analyst precision (4.1%). Different white light
      interferometry instrument parameters (autofocus, protective shield, syringe
      barrel dimensions input, type of non-siliconized syringe used as base reference)
      had no significant impact on the measured average layer thickness. The obtained
      values from white light interferometry applying a fully developed method (12
      radial lines, 50 mm measurement distance, 50 measurements points) were in
      agreement with orthogonal results from combined white and laser interferometry
      and 3D-laser scanning microscopy. The investigated syringe batches (lot A and B)
      exhibited comparable longitudinal silicone oil layer thicknesses ranging from 170
      190 nm to 90-100 nm from flange to tip and homogeneously distributed silicone
      layers over the syringe barrel circumference (110- 135 nm). Empty break-loose (4
      4.5 N) and gliding forces (2-2.5 N) were comparably low for both analyzed syringe
      lots. A silicone oil layer thickness of 100-200 nm was thus sufficient for
      adequate functionality in this particular study. Filling the syringe with a
      surrogate solution including short-term exposure and emptying did not
      significantly influence the silicone oil layer at the investigated silicone
      level. It thus appears reasonable to use this approach to characterize silicone
      oil layers in filled syringes over time. The developed method characterizes non
      destructively the layer thickness and distribution of silicone oil in empty
      syringes and provides fast access to reliable results. The gained information can
      be further used to support optimization of siliconization processes and increase
      the understanding of syringe functionality.LAY ABSTRACT: Silicone oil layers as
      lubricant are required to ensure functionality of prefilled syringes. Methods
      evaluating these layers are limited, and systematic evaluation is missing. The
      aim of this study was to develop and assess white light interferometry as an
      analytical method to characterize sprayed-on silicone oil layers in 1 mL
      prefilled syringes. White light interferometry showed a good accuracy (93-99%) as
      well as instrument and analyst precision (0.5% and 4.1%, respectively). Different
      applied instrument parameters had no significant impact on the measured layer
      thickness. The obtained values from white light interferometry applying a fully
      developed method concurred with orthogonal results from 3D-laser scanning
      microscopy and combined white light and laser interferometry. The average layer
      thicknesses in two investigated syringe lots gradually decreased from 170-190 nm
      at the flange to 100-90 nm at the needle side. The silicone layers were
      homogeneously distributed over the syringe barrel circumference (110-135 nm) for
      both lots. Empty break-loose (4-4.5 N) and gliding forces (2-2.5 N) were
      comparably low for both analyzed syringe lots. Syringe filling with a surrogate
      solution, including short-term exposure and emptying, did not significantly
      affect the silicone oil layer. The developed, non-destructive method provided
      reliable results to characterize the silicone oil layer thickness and
      distribution in empty siliconized syringes. This information can be further used
      to support optimization of siliconization processes and increase understanding of
      syringe functionality.

PMID- 29343618
TI  - Retention of Acholeplasma laidlawii by Sterile Filtration Membranes: Effect of
      Cultivation Medium and Filtration Temperature.
AB  - : This experimental study compares cell size, zeta potential, and the ability to
      penetrate tailor-made size exclusion membrane filters of mycoplasma Acholeplasma
      laidlawii cultivated in five different cultivation media. The influence of
      relevant filtration process parameters, in particular transmembrane pressure and
      filtration temperature, on their respective retention was tested. The impact of
      the filtration temperature was further evaluated for the Gram-negative bacteria
      species Brevundimonas diminuta, the Gram-positive bacteria species Staphylococcus
      epidermidis, the Pseudomonas phage PP7, and the mycoplasma species Mycoplasma
      orale The findings were correlated to the different mechanical properties of the
      particles, especially also with respect to the different bacterial cell envelopes
      found in those species. This study suggests that mycoplasma, surrounded by a
      flexible lipid bilayer, are significantly susceptible to changes in temperature,
      altering the stiffness of the cell envelope. Mycoplasma retention could thus be
      increased significantly by a decreased filtration temperature. In contrast, Gram
      negative and Gram-positive bacteria species, with a cell wall containing a cross
      linked peptidoglycan layer, as well as bacteriophages PP7 exhibiting a rigid
      protein capsid, did not show a temperature-dependent retention within the applied
      filtration temperatures between 2 and 35  degrees C. The trends of the retention
      of A. laidlawii with increasing temperature and transmembrane pressure were
      independent of cultivation media. Data obtained with mycoplasma M. orale suggest
      that the trend of mycoplasma retention at different filtration temperatures is
      also independent of the membrane pore size and thus retention level.LAY ABSTRACT:
      Media in biopharmaceutical processes are sterile-filtered to prevent them from
      bacterial contamination. Mycoplasma represent a relevant class of bacteria. In
      this publication it is shown that mycoplasma cell size depends on the media they
      are cultivated in. Membranes used for sterile filtration retain bacteria
      predominantly by size exclusion. Thus, an altered cell size can result in
      different retention values. Another characteristic of mycoplasma is the flexible
      lipid bilayer and the absence of a rigid cell wall. The lipid bilayer can undergo
      a phase transition from a gel to a liquid-crystal phase at a certain temperature,
      which makes it stiffer at lower temperatures. A higher stiffness can result in
      higher retention values during filtration, as the deformability of the mycoplasma
      cell is lower and the cell does not squeeze through the membrane pores.
      ABBREVIATIONS: ALCM: A. laidlawii culture medium; ASTM: American Society for
      Testing and Materials; ATCC: American Type Culture Collection; CFU/mL: colony
      forming units per milliliter; DLS: Dynamic light scattering; LRV: Log reduction
      value; PES: Polyethersulfone; PFU/mL: Plaque-forming units per milliliter; PSD:
      Particle size distribution; PVP: Polyvinylpyrrolidone; SDS: Sodium dodecyl
      sulfate; SEM: Scanning electron microscopy; SLB: Saline lactose broth; TMP:
      Transmembrane pressure; TSB: Tryptic soy broth.

PMID- 29343619
TI  - Quantitative Analysis of Vaccine Antigen Adsorption to Aluminum Adjuvant Using an
      Automated High-Throughput Method.
AB  - Aluminum-containing adjuvants have been widely used in vaccine formulations to
      safely and effectively potentiate the immune response. The examination of the
      extent of antigen adsorption to aluminum adjuvant is always evaluated during the
      development of aluminum adjuvant containing vaccines. A rapid, automated, high
      throughput assay was developed to measure antigen adsorption in a 96-well plate
      format using a TECAN Freedom EVO(r) (TECAN). The antigen adsorption levels at a
      constant adjuvant concentration for each sample were accurately measured at 12
      antigen/adjuvant (w/w) formulation ratios. These measurements were done at
      aluminum adjuvant concentrations similar to normal vaccine formulations, unlike
      previous non-automated and automated adjuvant adsorption studies. Two high
      sensitivity analytical methods were used to detect the non-absorbed antigens. The
      antigen-to-adjuvant adsorption curves were fit to a simple Langmuir adsorption
      model for quantitatively analyzing the antigen to the adjuvant adsorption level
      and strength. The interaction of two model antigens, bovine serum albumin and
      lysozyme, with three types of aluminum adjuvant, were quantitatively analyzed in
      this report. Automated, high-throughput methodologies combined with sensitive
      analytical methods are useful for accelerating practical vaccine formulation
      development.LAY ABSTRACT: Vaccines are probably the most effective public health
      method to prevent epidemics of many infectious diseases. Many of the most
      effective vaccines contain aluminum adjuvant. This report describes novel
      technology that can be used to better optimize the efficacy and stability of
      aluminum adjuvant-containing vaccines.

PMID- 29343620
TI  - Comparative Extractables Study of Autoclavable Polyethersulfone Filter Cartridges
      for Sterile Filtration.
AB  - Sterile filters are ubiquitous in biopharmaceutical manufacturing processes.
      Because such filters are in direct contact with the process fluid, profiling of
      the extractables is of utmost importance. The work presented here reveals the
      extractables profile from filter cartridges for sterilizing-grade filtration,
      which were obtained from six different vendors. All filters contain a 0.2 MUm
      polyethersulfone membrane for sterile filtration combined with a polyethersulfone
      pre-filter with retention rates spanning from 0.4 to 0.6 MUm. These filter
      cartridges are designed for use in stainless steel housings which allow for in
      line steam sterilization. A combination of different analytical techniques such
      as (headspace) gas chromatography-mass spectrometry, ultra-performance liquid
      chromatography-high-resolution mass spectrometry (electrospray ionization),
      inductively coupled plasma mass spectrometry, total organic carbon, non-volatile
      residue, conductivity, and pH value were applied to develop a comprehensive
      extractables profile on a qualitative and semi-quantitative basis. Pure ethanol
      and purified water were used as extraction media. The extractables profile
      consisted of various polyolefin-related extractables, additives such as
      antioxidants and degradation products thereof, hydrocarbons, and processing aids
      in addition to membrane-related extractables.LAY ABSTRACT: Filter cartridges or
      other filter products for sterile filtration are currently most commonly made of
      polymeric materials such as polypropylene, and a filter membrane material such as
      polyethersulfone. These materials will usually release chemical substances upon
      extraction in the laboratory (extractables), or upon application in
      biopharmaceutical processing (leachables). Potential extractables and leachables
      are additives used to tailor the physicochemical properties and to protect the
      polymeric materials, or degradants of these substances, or they arise from
      substances used during the manufacturing of the filter cartridges. Multiple
      analytical techniques were applied here to investigate the concentration and
      chemical nature of extractables obtained upon application of two distinct
      extraction solvents. Typical extractables found were antioxidants or releasing
      agents in addition to compounds originating from the polyethersulfone membrane.

PMID- 29343621
TI  - Impact of Stainless Steel Exposure on the Oxidation of Polysorbate 80 in
      Histidine Placebo and Active Monoclonal Antibody Formulation.
AB  - Rapid oxidation of polysorbate 80 in histidine buffer was observed upon brief
      exposure to stainless steel. Liquid chromatography-mass spectrometry analysis
      indicates degradation of both polyoxyethylene sorbitan and polyoxyethylene head
      groups and unsaturated fatty acid chains, with further confirmation by reversed
      phase high-performance liquid chromatography data. Both Fe2+ and Fe3+ were shown
      to induce polysorbate 80 oxidation. The degree of oxidation in polysorbate 20 and
      polysorbate 80 are comparable for the head groups and saturated fatty acid
      esters. However, the same phenomenon was not observed with placebo or monoclonal
      antibody at a threshold protein concentration, formulated in sodium citrate, in
      combination with histidine and sodium citrate, or with Na2
      ethylenediaminetetraacetic acid (EDTA). Further, polysorbate 80 oxidation was not
      observed with Lilly's antibody containing the active ingredient LY2951742, at or
      above a threshold concentration. Finally, no major polysorbate 80 degradation was
      observed in histidine buffer, with or without protein, in containers composed of
      glass or plastic, or when stainless steel exposure was otherwise completely
      absent. Finally, the 2-oxo oxidation form of histidine was not observed, but the
      other oxidation products and modifications of histidine were identified.LAY
      ABSTRACT: Rapid oxidation of polysorbate 80 in histidine buffer was observed upon
      brief exposure to stainless steel. The degree of oxidation in polysorbate 80 and
      polysorbate 20 were comparable. However, the same phenomenon was not observed
      with placebo when formulated in sodium citrate, in combination with histidine and
      sodium citrate, or with Na2 ethylenediaminetetraacetic acid (EDTA). Polysorbate
      80 oxidation was not observed with Lilly's antibody containing the active
      ingredient, LY2951742, at or above a threshold concentration. No major
      polysorbate 80 degradation in histidine buffer was observed when stainless steel
      contact was completely absent.

PMID- 29343622
TI  - Enhanced preclinical antitumor activity of M7824, a bifunctional fusion protein
      simultaneously targeting PD-L1 and TGF-beta.
AB  - Antibodies targeting immune checkpoints are emerging as potent and viable cancer
      therapies, but not all patients respond to these as single agents. Concurrently
      targeting additional immunosuppressive pathways is a promising approach to
      enhance immune checkpoint blockade, and bifunctional molecules designed to target
      two pathways simultaneously may provide a strategic advantage over the
      combination of two single agents. M7824 (MSB0011359C) is a bifunctional fusion
      protein composed of a monoclonal antibody against programmed death ligand 1 (PD
      L1) fused to the extracellular domain of human transforming growth factor-beta
      (TGF-beta) receptor II, which functions as a "trap" for all three TGF-beta
      isoforms. We demonstrate that M7824 efficiently, specifically, and simultaneously
      binds PD-L1 and TGF-beta. In syngeneic mouse models, M7824 suppressed tumor
      growth and metastasis more effectively than treatment with either an anti-PD-L1
      antibody or TGF-beta trap alone; furthermore, M7824 extended survival and
      conferred long-term protective antitumor immunity. Mechanistically, the dual anti
      immunosuppressive function of M7824 resulted in activation of both the innate and
      adaptive immune systems, which contributed to M7824's antitumor activity.
      Finally, M7824 was an effective combination partner for radiotherapy or
      chemotherapy in mouse models. Collectively, our preclinical data demonstrate that
      simultaneous blockade of the PD-L1 and TGF-beta pathways by M7824 elicits potent
      and superior antitumor activity relative to monotherapies.

PMID- 29343623
TI  - Identifying DNA methylation biomarkers for non-endoscopic detection of Barrett's
      esophagus.
AB  - We report a biomarker-based non-endoscopic method for detecting Barrett's
      esophagus (BE) based on detecting methylated DNAs retrieved via a swallowable
      balloon-based esophageal sampling device. BE is the precursor of, and a major
      recognized risk factor for, developing esophageal adenocarcinoma. Endoscopy, the
      current standard for BE detection, is not cost-effective for population
      screening. We performed genome-wide screening to ascertain regions targeted for
      recurrent aberrant cytosine methylation in BE, identifying high-frequency
      methylation within the CCNA1 locus. We tested CCNA1 DNA methylation as a BE
      biomarker in cytology brushings of the distal esophagus from 173 individuals with
      or without BE. CCNA1 DNA methylation demonstrated an area under the curve of 0.95
      for discriminating BE-related metaplasia and neoplasia cases versus normal
      individuals, performing identically to methylation of VIM DNA, an established BE
      biomarker. When combined, the resulting two biomarker panel was 95% sensitive and
      91% specific. These results were replicated in an independent validation cohort
      of 149 individuals who were assayed using the same cutoff values for test
      positivity established in the training population. To progress toward non
      endoscopic esophageal screening, we engineered a well-tolerated, swallowable,
      encapsulated balloon device able to selectively sample the distal esophagus
      within 5 min. In balloon samples from 86 individuals, tests of CCNA1 plus VIM DNA
      methylation detected BE metaplasia with 90.3% sensitivity and 91.7% specificity.
      Combining the balloon sampling device with molecular assays of CCNA1 plus VIM DNA
      methylation enables an efficient, well-tolerated, sensitive, and specific method
      of screening at-risk populations for BE.

PMID- 29343624
TI  - Inhalation of peptide-loaded nanoparticles improves heart failure.
AB  - Peptides are highly selective and efficacious for the treatment of cardiovascular
      and other diseases. However, it is currently not possible to administer peptides
      for cardiac-targeting therapy via a noninvasive procedure, thus representing
      scientific and technological challenges. We demonstrate that inhalation of small
      (<50 nm in diameter) biocompatible and biodegradable calcium phosphate
      nanoparticles (CaPs) allows for rapid translocation of CaPs from the pulmonary
      tree to the bloodstream and to the myocardium, where their cargo is quickly
      released. Treatment of a rodent model of diabetic cardiomyopathy by inhalation of
      CaPs loaded with a therapeutic mimetic peptide that we previously demonstrated to
      improve myocardial contraction resulted in restoration of cardiac function.
      Translation to a porcine large animal model provides evidence that inhalation of
      a peptide-loaded CaP formulation is an effective method of targeted
      administration to the heart. Together, these results demonstrate that inhalation
      of biocompatible tailored peptide nanocarriers represents a pioneering approach
      for the pharmacological treatment of heart failure.

PMID- 29343625
TI  - Methicillin-resistant Staphylococcus aureus causes sustained collecting lymphatic
      vessel dysfunction.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of morbidity
      and mortality worldwide and is a frequent cause of skin and soft tissue
      infections (SSTIs). Lymphedema-fluid accumulation in tissue caused by impaired
      lymphatic vessel function-is a strong risk factor for SSTIs. SSTIs also
      frequently recur in patients and sometimes lead to acquired lymphedema. However,
      the mechanism of how SSTIs can be both the consequence and the cause of lymphatic
      vessel dysfunction is not known. Intravital imaging in mice revealed an acute
      reduction in both lymphatic vessel contractility and lymph flow after localized
      MRSA infection. Moreover, chronic lymphatic impairment is observed long after
      MRSA is cleared and inflammation is resolved. Associated with decreased
      collecting lymphatic vessel function was the loss and disorganization of
      lymphatic muscle cells (LMCs), which are critical for lymphatic contraction. In
      vitro, incubation with MRSA-conditioned supernatant led to LMC death. Proteomic
      analysis identified several accessory gene regulator (agr)-controlled MRSA
      exotoxins that contribute to LMC death. Infection with agr mutant MRSA resulted
      in sustained lymphatic function compared to animals infected with wild-type MRSA.
      Our findings suggest that agr is a promising target to preserve lymphatic vessel
      function and promote immunity during SSTIs.

PMID- 29343626
TI  - Engineering precision biomaterials for personalized medicine.
AB  - As the demand for precision medicine continues to rise, the "one-size-fits-all"
      approach to designing medical devices and therapies is becoming increasingly
      outdated. Biomaterials have considerable potential for transforming precision
      medicine, but individual patient complexity often necessitates integrating
      multiple functions into a single device to successfully tailor personalized
      therapies. Here, we introduce an engineering strategy based on unit operations to
      provide a unified vocabulary and contextual framework to aid the design of
      biomaterial-based devices and accelerate their translation.

PMID- 29343627
TI  - Risk ratios for contagious outcomes.
AB  - Epidemiologists commonly use the risk ratio to summarize the relationship between
      a binary covariate and outcome, even when outcomes may be dependent.
      Investigations of transmissible diseases in clusters-households, villages or
      small groups-often report risk ratios. Epidemiologists have warned that risk
      ratios may be misleading when outcomes are contagious, but the nature of this
      error is poorly understood. In this study, we assess the meaning of the risk
      ratio when outcomes are contagious. We provide a mathematical definition of
      infectious disease transmission within clusters, based on the canonical
      stochastic susceptible-infective model. From this characterization, we define the
      individual-level ratio of instantaneous infection risks as the inferential
      target, and evaluate the properties of the risk ratio as an approximation of this
      quantity. We exhibit analytically and by simulation the circumstances under which
      the risk ratio implies an effect whose direction is opposite that of the true
      effect of the covariate. In particular, the risk ratio can be greater than one
      even when the covariate reduces both individual-level susceptibility to
      infection, and transmissibility once infected. We explain these findings in the
      epidemiologic language of confounding and Simpson's paradox, underscoring the
      pitfalls of failing to account for transmission when outcomes are contagious.

PMID- 29343629
TI  - The Markov blankets of life: autonomy, active inference and the free energy
      principle.
AB  - This work addresses the autonomous organization of biological systems. It does so
      by considering the boundaries of biological systems, from individual cells to
      Home sapiens, in terms of the presence of Markov blankets under the active
      inference scheme-a corollary of the free energy principle. A Markov blanket
      defines the boundaries of a system in a statistical sense. Here we consider how a
      collective of Markov blankets can self-assemble into a global system that itself
      has a Markov blanket; thereby providing an illustration of how autonomous systems
      can be understood as having layers of nested and self-sustaining boundaries. This
      allows us to show that: (i) any living system is a Markov blanketed system and
      (ii) the boundaries of such systems need not be co-extensive with the biophysical
      boundaries of a living organism. In other words, autonomous systems are
      hierarchically composed of Markov blankets of Markov blankets-all the way down to
      individual cells, all the way up to you and me, and all the way out to include
      elements of the local environment.

PMID- 29343630
TI  - Emergence and dynamics of self-producing information niches as a step towards pre
      evolutionary organization.
AB  - As a step towards understanding pre-evolutionary organization in non-genetic
      systems, we develop a model to investigate the emergence and dynamics of proto
      autopoietic networks in an interacting population of simple information
      processing entities (automata). Our simulations indicate that dynamically stable
      strongly connected networks of mutually producing communication channels emerge
      under specific environmental conditions. We refer to these distinct
      organizational steady states as information niches In each case, we measure the
      information content by the Shannon entropy, and determine the fitness landscape,
      robustness and transition pathways for information niches subjected to
      intermittent environmental perturbations under non-evolutionary conditions. By
      determining the information required to generate each niche, we show that niche
      transitions are only allowed if accompanied by an equal or increased level of
      information production that arises internally or via environmental perturbations
      that serve as an exogenous source of population diversification. Overall, our
      simulations show how proto-autopoietic networks of basic information processors
      form and compete, and under what conditions they persist over time or go extinct.
      These findings may be relevant to understanding how inanimate systems such as
      chemically communicating protocells can initiate the transition to living matter
      prior to the onset of contemporary evolutionary and genetic mechanisms.

PMID- 29343628
TI  - Keeping the home fires burning: AMP-activated protein kinase.
AB  - Living cells obtain energy either by oxidizing reduced compounds of organic or
      mineral origin or by absorbing light. Whichever energy source is used, some of
      the energy released is conserved by converting adenosine diphosphate (ADP) to
      adenosine triphosphate (ATP), which are analogous to the chemicals in a
      rechargeable battery. The energy released by the conversion of ATP back to ADP is
      used to drive most energy-requiring processes, including cell growth, cell
      division, communication and movement. It is clearly essential to life that the
      production and consumption of ATP are always maintained in balance, and the AMP
      activated protein kinase (AMPK) is one of the key cellular regulatory systems
      that ensures this. In eukaryotic cells (cells with nuclei and other internal
      membrane-bound structures, including human cells), most ATP is produced in
      mitochondria, which are thought to have been derived by the engulfment of
      oxidative bacteria by a host cell not previously able to use molecular oxygen.
      AMPK is activated by increasing AMP or ADP (AMP being generated from ADP whenever
      ADP rises) coupled with falling ATP. Relatives of AMPK are found in essentially
      all eukaryotes, and it may have evolved to allow the host cell to monitor the
      output of the newly acquired mitochondria and step their ATP production up or
      down according to the demand. Structural studies have illuminated how AMPK
      achieves the task of detecting small changes in AMP and ADP, despite the presence
      of much higher concentrations of ATP. Recently, it has been shown that AMPK can
      also sense the availability of glucose, the primary carbon source for most
      eukaryotic cells, via a mechanism independent of changes in AMP or ADP. Once
      activated by energy imbalance or glucose lack, AMPK modifies many target proteins
      by transferring phosphate groups to them from ATP. By this means, numerous ATP
      producing processes are switched on (including the production of new
      mitochondria) and ATP-consuming processes are switched off, thus restoring energy
      homeostasis. Drugs that modulate AMPK have great potential in the treatment of
      metabolic disorders such as obesity and Type 2 diabetes, and even cancer. Indeed,
      some existing drugs such as metformin and aspirin, which were derived from
      traditional herbal remedies, appear to work, in part, by activating AMPK.

PMID- 29343631
TI  - Stochastic resonances in a distributed genetic broadcasting system: the
      NFkappaB/IkappaB paradigm.
AB  - Gene regulatory networks must relay information from extracellular signals to
      downstream genes in an efficient, timely and coherent manner. Many complex
      functional tasks such as the immune response require system-wide broadcasting of
      information not to one but to many genes carrying out distinct functions whose
      dynamical binding and unbinding characteristics are widely distributed. In such
      broadcasting networks, the intended target sites are also often dwarfed in number
      by the even more numerous non-functional binding sites. Taking the genetic
      regulatory network of NFkappaB as an exemplary system we explore the impact of
      having numerous distributed sites on the stochastic dynamics of oscillatory
      broadcasting genetic networks pointing out how resonances in binding cycles
      control the network's specificity and performance. We also show that active
      kinetic regulation of binding and unbinding through molecular stripping of DNA
      bound transcription factors can lead to a higher coherence of gene-co-expression
      and synchronous clearance.

PMID- 29343632
TI  - Correction to 'Dynamics of phytoplankton blooms in turbulent vortex cells'.

PMID- 29343634
TI  - Fluttering of growing leaves as a way to reach flatness: experimental evidence on
      Persea americana.
AB  - Simple leaves show unexpected growth motions: the midrib of the leaves swings
      periodically in association with buckling events of the leaf blade, giving the
      impression that the leaves are fluttering. The quantitative kinematic analysis of
      this motion provides information about the respective growth between the main
      vein and the lamina. Our three-dimensional reconstruction of an avocado tree leaf
      shows that the conductor of the motion is the midrib, presenting continuous
      oscillations and inducing buckling events on the blade. The variations in the
      folding angle of the leaf show that the lamina is not passive: it responds to the
      deformation induced by the connection to the midrib to reach a globally flat
      state. We model this movement as an asymmetric growth of the midrib, which
      directs an inhomogeneous growth of the lamina, and we suggest how the transition
      from the folded state to the flat state is mechanically organized.

PMID- 29343635
TI  - Combining radiation with hyperthermia: a multiscale model informed by in vitro
      experiments.
AB  - Combined radiotherapy and hyperthermia offer great potential for the successful
      treatment of radio-resistant tumours through thermo-radiosensitization. Tumour
      response heterogeneity, due to intrinsic, or micro-environmentally induced
      factors, may greatly influence treatment outcome, but is difficult to account for
      using traditional treatment planning approaches. Systems oncology simulation,
      using mathematical models designed to predict tumour growth and treatment
      response, provides a powerful tool for analysis and optimization of combined
      treatments. We present a framework that simulates such combination treatments on
      a cellular level. This multiscale hybrid cellular automaton simulates large cell
      populations (up to 107 cells) in vitro, while allowing individual cell-cycle
      progression, and treatment response by modelling radiation-induced mitotic cell
      death, and immediate cell kill in response to heating. Based on a calibration
      using a number of experimental growth, cell cycle and survival datasets for
      HCT116 cells, model predictions agreed well (R2 > 0.95) with experimental data
      within the range of (thermal and radiation) doses tested (0-40 CEM43, 0-5 Gy).
      The proposed framework offers flexibility for modelling multimodality treatment
      combinations in different scenarios. It may therefore provide an important step
      towards the modelling of personalized therapies using a virtual patient tumour.

PMID- 29343633
TI  - Hydrogel biomaterials and their therapeutic potential for muscle injuries and
      muscular dystrophies.
AB  - Muscular diseases such as muscular dystrophies and muscle injuries constitute a
      large group of ailments that manifest as muscle weakness, atrophy or fibrosis.
      Although cell therapy is a promising treatment option, the delivery and retention
      of cells in the muscle is difficult and prevents sustained regeneration needed
      for adequate functional improvements. Various types of biomaterials with
      different physical and chemical properties have been developed to improve the
      delivery of cells and/or growth factors for treating muscle injuries. Hydrogels
      are a family of materials with distinct advantages for use as cell delivery
      systems in muscle injuries and ailments, including their mild processing
      conditions, their similarities to natural tissue extracellular matrix, and their
      ability to be delivered with less invasive approaches. Moreover, hydrogels can be
      made to completely degrade in the body, leaving behind their biological payload
      in a process that can enhance the therapeutic process. For these reasons,
      hydrogels have shown great potential as cell delivery matrices. This paper
      reviews a few of the hydrogel systems currently being applied together with cell
      therapy and/or growth factor delivery to promote the therapeutic repair of muscle
      injuries and muscle wasting diseases such as muscular dystrophies.

PMID- 29343636
TI  - Non-cell autonomous control of precerebellar neuron migration by Slit and Robo
      proteins.
AB  - During development, precerebellar neurons migrate tangentially from the dorsal
      hindbrain to the floor plate. Their axons cross it but their cell bodies stop
      their ventral migration upon reaching the midline. It has previously been shown
      that Slit chemorepellents and their receptors, Robo1 and Robo2, might control the
      migration of precerebellar neurons in a repulsive manner. Here, we have used a
      conditional knockout strategy in mice to test this hypothesis. We show that the
      targeted inactivation of the expression of Robo1 and Robo2 receptors in
      precerebellar neurons does not perturb their migration and that they still stop
      at the midline. The selective ablation of the expression of all three Slit
      proteins in floor-plate cells has no effect on pontine neurons and only induces
      the migration of a small subset of inferior olivary neurons across the floor
      plate. Likewise, we show that the expression of Slit proteins in the facial
      nucleus is dispensable for pontine neuron migration. Together, these results show
      that Robo1 and Robo2 receptors act non-cell autonomously in migrating
      precerebellar neurons and that floor-plate signals, other than Slit proteins,
      must exist to prevent midline crossing.

PMID- 29343638
TI  - Commissural neurons transgress the CNS/PNS boundary in absence of ventricular
      zone-derived netrin 1.
AB  - During the development of the central nervous system (CNS), only motor axons
      project into peripheral nerves. Little is known about the cellular and molecular
      mechanisms that control the development of a boundary at the CNS surface and
      prevent CNS neuron emigration from the neural tube. It has previously been shown
      that a subset of spinal cord commissural axons abnormally invades sensory nerves
      in Ntn1 hypomorphic embryos and Dcc knockouts. However, whether netrin 1 also
      plays a similar role in the brain is unknown. In the hindbrain, precerebellar
      neurons migrate tangentially under the pial surface, and their ventral migration
      is guided by netrin 1. Here, we show that pontine neurons and inferior olivary
      neurons, two types of precerebellar neurons, are not confined to the CNS in Ntn1
      and Dcc mutant mice, but that they invade the trigeminal, auditory and vagus
      nerves. Using a Ntn1 conditional knockout, we show that netrin 1, which is
      released at the pial surface by ventricular zone progenitors is responsible for
      the CNS confinement of precerebellar neurons. We propose, that netrin 1
      distribution sculpts the CNS boundary by keeping CNS neurons in netrin 1-rich
      domains.

PMID- 29343639
TI  - Neural migration: re-evaluating Slit and Robo.

PMID- 29343637
TI  - Tyrosine phosphorylation and proteolytic cleavage of Notch are required for non
      canonical Notch/Abl signaling in Drosophila axon guidance.
AB  - Notch signaling is required for the development and physiology of nearly every
      tissue in metazoans. Much of Notch signaling is mediated by transcriptional
      regulation of downstream target genes, but Notch controls axon patterning in
      Drosophila by local modulation of Abl tyrosine kinase signaling, via direct
      interactions with the Abl co-factors Disabled and Trio. Here, we show that Notch
      Abl axonal signaling requires both of the proteolytic cleavage events that
      initiate canonical Notch signaling. We further show that some Notch protein is
      tyrosine phosphorylated in Drosophila, that this form of the protein is
      selectively associated with Disabled and Trio, and that relevant tyrosines are
      essential for Notch-dependent axon patterning but not for canonical Notch
      dependent regulation of cell fate. Based on these data, we propose a model for
      the molecular mechanism by which Notch controls Abl signaling in Drosophila
      axons.

PMID- 29343640
TI  - Single-cell transcriptomics of the developing lateral geniculate nucleus reveals
      insights into circuit assembly and refinement.
AB  - Coordinated changes in gene expression underlie the early patterning and cell
      type specification of the central nervous system. However, much less is known
      about how such changes contribute to later stages of circuit assembly and
      refinement. In this study, we employ single-cell RNA sequencing to develop a
      detailed, whole-transcriptome resource of gene expression across four time points
      in the developing dorsal lateral geniculate nucleus (LGN), a visual structure in
      the brain that undergoes a well-characterized program of postnatal circuit
      development. This approach identifies markers defining the major LGN cell types,
      including excitatory relay neurons, oligodendrocytes, astrocytes, microglia, and
      endothelial cells. Most cell types exhibit significant transcriptional changes
      across development, dynamically expressing genes involved in distinct processes
      including retinotopic mapping, synaptogenesis, myelination, and synaptic
      refinement. Our data suggest that genes associated with synapse and circuit
      development are expressed in a larger proportion of nonneuronal cell types than
      previously appreciated. Furthermore, we used this single-cell expression atlas to
      identify the Prkcd-Cre mouse line as a tool for selective manipulation of relay
      neurons during a late stage of sensory-driven synaptic refinement. This
      transcriptomic resource provides a cellular map of gene expression across several
      cell types of the LGN, and offers insight into the molecular mechanisms of
      circuit development in the postnatal brain.

PMID- 29343641
TI  - Degradation of FBXO31 by APC/C is regulated by AKT- and ATM-mediated
      phosphorylation.
AB  - The F-box protein FBXO31 is a tumor suppressor that is encoded in 16q24.3, for
      which there is loss of heterozygosity in various solid tumors. FBXO31 serves as
      the substrate-recognition component of the SKP/Cullin/F-box protein class of E3
      ubiquitin ligases and has been shown to direct degradation of pivotal cell-cycle
      regulatory proteins including cyclin D1 and the p53 antagonist MDM2. FBXO31
      levels are normally low but increase substantially following genotoxic stress
      through a mechanism that remains to be determined. Here we show that the low
      levels of FBXO31 are maintained through proteasomal degradation by anaphase
      promoting complex/cyclosome (APC/C). We find that the APC/C coactivators CDH1 and
      CDC20 bind to a destruction-box (D-box) motif present in FBXO31 to promote its
      polyubiquitination and degradation in a cell-cycle-regulated manner, which
      requires phosphorylation of FBXO31 on serine-33 by the prosurvival kinase AKT.
      Following genotoxic stress, phosphorylation of FBXO31 on serine-278 by another
      kinase, the DNA damage kinase ATM, results in disruption of its interaction with
      CDH1 and CDC20, thereby preventing FBXO31 degradation. Collectively, our results
      reveal how alterations in FBXO31 phosphorylation, mediated by AKT and ATM,
      underlie physiological regulation of FBXO31 levels in unstressed and
      genotoxically stressed cells.

PMID- 29343642
TI  - Mechanogenetics for the remote and noninvasive control of cancer immunotherapy.
AB  - While cell-based immunotherapy, especially chimeric antigen receptor (CAR)
      expressing T cells, is becoming a paradigm-shifting therapeutic approach for
      cancer treatment, there is a lack of general methods to remotely and
      noninvasively regulate genetics in live mammalian cells and animals for cancer
      immunotherapy within confined local tissue space. To address this limitation, we
      have identified a mechanically sensitive Piezo1 ion channel (mechanosensor) that
      is activatable by ultrasound stimulation and integrated it with engineered
      genetic circuits (genetic transducer) in live HEK293T cells to convert the
      ultrasound-activated Piezo1 into transcriptional activities. We have further
      engineered the Jurkat T-cell line and primary T cells (peripheral blood
      mononuclear cells) to remotely sense the ultrasound wave and transduce it into
      transcriptional activation for the CAR expression to recognize and eradicate
      target tumor cells. This approach is modular and can be extended for remote
      controlled activation of different cell types with high spatiotemporal precision
      for therapeutic applications.

PMID- 29343643
TI  - Pyridoxal-5'-phosphate as an oxygenase cofactor: Discovery of a carboxamide
      forming, alpha-amino acid monooxygenase-decarboxylase.
AB  - Capuramycins are antimycobacterial antibiotics that consist of a modified
      nucleoside named uridine-5'-carboxamide (CarU). Previous biochemical studies have
      revealed that CarU is derived from UMP, which is first converted to uridine-5'
      aldehyde in a reaction catalyzed by the dioxygenase CapA and subsequently to 5'-C
      glycyluridine (GlyU), an unusual beta-hydroxy-alpha-amino acid, in a reaction
      catalyzed by the pyridoxal-5'-phosphate (PLP)-dependent transaldolase CapH. The
      remaining steps that are necessary to furnish CarU include decarboxylation, O
      atom insertion, and oxidation. We demonstrate that Cap15, which has sequence
      similarity to proteins annotated as bacterial, PLP-dependent l-seryl-tRNA(Sec)
      selenium transferases, is the sole catalyst responsible for complete conversion
      of GlyU to CarU. Using a complementary panel of in vitro assays, Cap15 is shown
      to be dependent upon substrates O2 and (5'S,6'R)-GlyU, the latter of which was
      unexpected given that (5'S,6'S)-GlyU is the isomeric product of the transaldolase
      CapH. The two products of Cap15 are identified as the carboxamide-containing CarU
      and CO2 While known enzymes that catalyze this type of chemistry, namely alpha
      amino acid 2-monooxygenase, utilize flavin adenine dinucleotide as the redox
      cofactor, Cap15 remarkably requires only PLP. Furthermore, Cap15 does not produce
      hydrogen peroxide and is shown to directly incorporate a single O atom from O2
      into the product CarU and thus is an authentic PLP-dependent monooxygenase. In
      addition to these unusual discoveries, Cap15 activity is revealed to be dependent
      upon the inclusion of phosphate. The biochemical characteristics along with
      initiatory mechanistic studies of Cap15 are reported, which has allowed us to
      assign Cap15 as a PLP-dependent (5'S,6'R)-GlyU:O2 monooxygenase-decarboxylase.

PMID- 29343644
TI  - Identification of genes required for Mycobacterium abscessus growth in vivo with
      a prominent role of the ESX-4 locus.
AB  - Mycobacterium abscessus, a rapidly growing mycobacterium (RGM) and an
      opportunistic human pathogen, is responsible for a wide spectrum of clinical
      manifestations ranging from pulmonary to skin and soft tissue infections. This
      intracellular organism can resist the bactericidal defense mechanisms of amoebae
      and macrophages, an ability that has not been observed in other RGM. M. abscessus
      can up-regulate several virulence factors during transient infection of amoebae,
      thereby becoming more virulent in subsequent respiratory infections in mice.
      Here, we sought to identify the M. abscessus genes required for replication
      within amoebae. To this end, we constructed and screened a transposon (Tn)
      insertion library of an M. abscessus subspecies massiliense clinical isolate for
      attenuated clones. This approach identified five genes within the ESX-4 locus,
      which in M. abscessus encodes an ESX-4 type VII secretion system that
      exceptionally also includes the ESX conserved EccE component. To confirm the
      screening results and to get further insight into the contribution of ESX-4 to M.
      abscessus growth and survival in amoebae and macrophages, we generated a deletion
      mutant of eccB4 that encodes a core structural element of ESX-4. This mutant was
      less efficient at blocking phagosomal acidification than its parental strain.
      Importantly, and in contrast to the wild-type strain, it also failed to damage
      phagosomes and showed reduced signs of phagosome-to-cytosol contact, as
      demonstrated by a combination of cellular and immunological assays. This study
      attributes an unexpected and genuine biological role to the underexplored
      mycobacterial ESX-4 system and its substrates.

PMID- 29343645
TI  - Crystal structure of the mammalian lipopolysaccharide detoxifier.
AB  - LPS is a potent bacterial endotoxin that triggers the innate immune system.
      Proper recognition of LPS by pattern-recognition receptors requires a full
      complement of typically six acyl chains in the lipid portion. Acyloxyacyl
      hydrolase (AOAH) is a host enzyme that removes secondary (acyloxyacyl-linked)
      fatty acids from LPS, rendering it immunologically inert. This activity is
      critical for recovery from immune tolerance that follows Gram-negative infection.
      To understand the molecular mechanism of AOAH function, we determined its crystal
      structure and its complex with LPS. The substrate's lipid moiety is accommodated
      in a large hydrophobic pocket formed by the saposin and catalytic domains with a
      secondary acyl chain inserted into a narrow lateral hydrophobic tunnel at the
      active site. The enzyme establishes dispensable contacts with the phosphate
      groups of LPS but does not interact with its oligosaccharide portion. Proteolytic
      processing allows movement of an amphipathic helix possibly involved in substrate
      access at membranes.

PMID- 29343646
TI  - Role of boundary conditions in determining cell alignment in response to stretch.
AB  - The ability of cells to orient in response to mechanical stimuli is essential to
      embryonic development, cell migration, mechanotransduction, and other critical
      physiologic functions in a range of organs. Endothelial cells, fibroblasts,
      mesenchymal stem cells, and osteoblasts all orient perpendicular to an applied
      cyclic stretch when plated on stretchable elastic substrates, suggesting a common
      underlying mechanism. However, many of these same cells orient parallel to
      stretch in vivo and in 3D culture, and a compelling explanation for the different
      orientation responses in 2D and 3D has remained elusive. Here, we conducted a
      series of experiments designed specifically to test the hypothesis that
      differences in strains transverse to the primary loading direction give rise to
      the different alignment patterns observed in 2D and 3D cyclic stretch experiments
      ("strain avoidance"). We found that, in static or low-frequency stretch
      conditions, cell alignment in fibroblast-populated collagen gels correlated with
      the presence or absence of a restraining boundary condition rather than with
      compaction strains. Cyclic stretch could induce perpendicular alignment in 3D
      culture but only at frequencies an order of magnitude greater than reported to
      induce perpendicular alignment in 2D. We modified a published model of stress
      fiber dynamics and were able to reproduce our experimental findings across all
      conditions tested as well as published data from 2D cyclic stretch experiments.
      These experimental and model results suggest an explanation for the apparently
      contradictory alignment responses of cells subjected to cyclic stretch on 2D
      membranes and in 3D gels.

PMID- 29343647
TI  - On the folding of a structurally complex protein to its metastable active state.
AB  - For successful protease inhibition, the reactive center loop (RCL) of the two
      domain serine protease inhibitor, alpha1-antitrypsin (alpha1-AT), needs to remain
      exposed in a metastable active conformation. The alpha1-AT RCL is sequestered in
      a beta-sheet in the stable latent conformation. Thus, to be functional, alpha1-AT
      must always fold to a metastable conformation while avoiding folding to a stable
      conformation. We explore the structural basis of this choice using folding
      simulations of coarse-grained structure-based models of the two alpha1-AT
      conformations. Our simulations capture the key features of folding experiments
      performed on both conformations. The simulations also show that the free energy
      barrier to fold to the latent conformation is much larger than the barrier to
      fold to the active conformation. An entropically stabilized on-pathway
      intermediate lowers the barrier for folding to the active conformation. In this
      intermediate, the RCL is in an exposed configuration, and only one of the two
      alpha1-AT domains is folded. In contrast, early conversion of the RCL into a beta
      strand increases the coupling between the two alpha1-AT domains in the transition
      state and creates a larger barrier for folding to the latent conformation. Thus,
      unlike what happens in several proteins, where separate regions promote folding
      and function, the structure of the RCL, formed early during folding, determines
      both the conformational and the functional fate of alpha1-AT. Further, the short
      12-residue RCL modulates the free energy barrier and the folding cooperativity of
      the large 370-residue alpha1-AT. Finally, we suggest experiments to test the
      predicted folding mechanism for the latent state.

PMID- 29343649
TI  - Topological transformations of Hopf solitons in chiral ferromagnets and liquid
      crystals.
AB  - Liquid crystals are widely known for their facile responses to external fields,
      which forms a basis of the modern information display technology. However,
      switching of molecular alignment field configurations typically involves
      topologically trivial structures, although singular line and point defects often
      appear as short-lived transient states. Here, we demonstrate electric and
      magnetic switching of nonsingular solitonic structures in chiral nematic and
      ferromagnetic liquid crystals. These topological soliton structures are
      characterized by Hopf indices, integers corresponding to the numbers of times
      that closed-loop-like spatial regions (dubbed "preimages") of two different
      single orientations of rod-like molecules or magnetization are linked with each
      other. We show that both dielectric and ferromagnetic response of the studied
      material systems allow for stabilizing a host of topological solitons with
      different Hopf indices. The field transformations during such switching are
      continuous when Hopf indices remain unchanged, even when involving
      transformations of preimages, but discontinuous otherwise.

PMID- 29343650
TI  - Decoder calibration with ultra small current sample set for intracortical brain
      machine interface.
AB  - OBJECTIVE: Intracortical brain-machine interfaces (iBMIs) aim to restore
      efficient communication and movement ability for paralyzed patients. However,
      frequent recalibration is required for consistency and reliability, and every
      recalibration will require relatively large most current sample set. The aim in
      this study is to develop an effective decoder calibration method that can achieve
      good performance while minimizing recalibration time. APPROACH: Two rhesus
      macaques implanted with intracortical microelectrode arrays were trained
      separately on movement and sensory paradigm. Neural signals were recorded to
      decode reaching positions or grasping postures. A novel principal component
      analysis-based domain adaptation (PDA) method was proposed to recalibrate the
      decoder with only ultra small current sample set by taking advantage of large
      historical data, and the decoding performance was compared with other three
      calibration methods for evaluation. MAIN RESULTS: The PDA method closed the gap
      between historical and current data effectively, and made it possible to take
      advantage of large historical data for decoder recalibration in current data
      decoding. Using only ultra small current sample set (five trials of each
      category), the decoder calibrated using the PDA method could achieve much better
      and more robust performance in all sessions than using other three calibration
      methods in both monkeys. SIGNIFICANCE: (1) By this study, transfer learning
      theory was brought into iBMIs decoder calibration for the first time. (2)
      Different from most transfer learning studies, the target data in this study were
      ultra small sample set and were transferred to the source data. (3) By taking
      advantage of historical data, the PDA method was demonstrated to be effective in
      reducing recalibration time for both movement paradigm and sensory paradigm,
      indicating a viable generalization. By reducing the demand for large current
      training data, this new method may facilitate the application of intracortical
      brain-machine interfaces in clinical practice.

PMID- 29343648
TI  - PAR1 agonists stimulate APC-like endothelial cytoprotection and confer resistance
      to thromboinflammatory injury.
AB  - Stimulation of protease-activated receptor 1 (PAR1) on endothelium by activated
      protein C (APC) is protective in several animal models of disease, and APC has
      been used clinically in severe sepsis and wound healing. Clinical use of APC,
      however, is limited by its immunogenicity and its anticoagulant activity. We show
      that a class of small molecules termed "parmodulins" that act at the cytosolic
      face of PAR1 stimulates APC-like cytoprotective signaling in endothelium.
      Parmodulins block thrombin generation in response to inflammatory mediators and
      inhibit platelet accumulation on endothelium cultured under flow. Evaluation of
      the antithrombotic mechanism showed that parmodulins induce cytoprotective
      signaling through Gbetagamma, activating a PI3K/Akt pathway and eliciting a
      genetic program that includes suppression of NF-kappaB-mediated transcriptional
      activation and up-regulation of select cytoprotective transcripts. STC1 is among
      the up-regulated transcripts, and knockdown of stanniocalin-1 blocks the
      protective effects of both parmodulins and APC. Induction of this signaling
      pathway in vivo protects against thromboinflammatory injury in blood vessels.
      Small-molecule activation of endothelial cytoprotection through PAR1 represents
      an approach for treatment of thromboinflammatory disease and provides proof-of
      principle for the strategy of targeting the cytoplasmic surface of GPCRs to
      achieve pathway selective signaling.

PMID- 29343651
TI  - Determining patient selection tool and response predictor for outpatient 30 mCi
      radioiodine ablation dose in non-metastatic differentiated thyroid carcinoma: a
      Japanese perspective.
AB  - The lack of isolation ward throughout Japan has long been limiting the 131I
      radioactive iodine (RAI) ablation for differentiated thyroid cancer (DTC) cases.
      The 30 mCi RAI ablation was only recently permitted for outpatient basis.
      However, no patient selection tool nor response predictor has been proposed. This
      study evaluated factors to find response predictor and determinant for the
      suitable patients. The retrospective study reviewed 47 eligible non-metastatic
      papillary DTC patients whose had first 30 mCi RAI ablation after total
      thyroidectomy. Age, gender, clinical stage, risk category, and pre-ablation serum
      thyroglobulin (Tg) level were among covariates analyzed to determine the patient
      selection factors; while the thyroid bed uptake on initial whole body scan (WBS)
      was later also included in determining RAI ablation response. Thirteen (28%)
      patients had a low risk (T1-2) while 23 (49%) and 11 (23%) had an intermediate
      (T3) or high risk (T4), respectively. Twenty-five patients were responders, and
      22 were non-responders. All factors were similar between responders and non
      responders except pre-ablation serum Tg level (p < 0.001). In multivariate
      analysis, pre-ablation serum Tg level was the only significant factor for both
      patient selection (odd ratio (OR) = 1.52, 95% confidence interval (CI) = 1.13
      2.06) and response predictor (OR = 1.48; 95% CI = 1.12-1.95). With the cut-off of
      5.4 ng/mL, pre-ablation serum Tg level predicts RAI ablation response with 92%
      specificity and 73% sensitivity. Pre-ablation serum Tg level may help patient
      selection and predict the response to outpatient 30 mCi RAI ablation among post
      total thyroidectomy non-metastatic DTC patients.

PMID- 29343652
TI  - Painless Thyroiditis and Fulminant Type 1 Diabetes Mellitus in a Patient Treated
      with an Immune Checkpoint Inhibitor, Nivolumab.
AB  - The programmed cell death-1 (PD-1) pathway is a novel therapeutic target in
      immune checkpoint therapy for cancer. Nivolumab, an anti-PD-1 monoclonal
      antibody, blocks PD-1 and can restore anti-cancer immune responses by disrupting
      the signal that inhibits T-cell activation. Nivolumab may induce endocrine
      related adverse events, including hypophysitis, autoimmune thyroiditis, and type
      1 diabetes mellitus. Here we report a 68-year-old female patient with advanced
      renal cell carcinoma who was treated with nivolumab. She had positive anti
      thyroglobulin antibodies and anti-thyroid peroxidase antibodies with slightly
      elevated thyroid-stimulating hormone (9.048 MUU/mL), and was diagnosed as chronic
      thyroiditis with subclinical hypothyroidism before nivolumab therapy. She
      developed painless thyroiditis after the first cycle of the therapy (Day 14). At
      the 7th cycle of nivolumab therapy (Day 98), hyperglycemia (473 mg/dL) was noted,
      whereas glycated hemoglobin level was 6.9%. Islet-related autoantibodies were all
      negative. The glucagon tolerance test showed complete depletion of insulin. Human
      leukocyte antigen typing showed haplotype DRB1*09:01-DQB1*03:03, which was
      reported to be closely associated with type 1 diabetes mellitus in Japan.
      Fulminant type 1 diabetes mellitus was diagnosed, and she was immediately treated
      with multiple daily injections of insulin. Fulminant type 1 diabetes mellitus is
      characterized by rapid-onset diabetic ketoacidosis, and negative islet-related
      autoantibodies, and was proposed as a novel subtype of non-autoimmune diabetes.
      Preceding painless thyroiditis with positive thyroid autoantibodies observed in
      the present case, however, raises the possibility that autoimmune mechanisms are
      involved in the pathogenesis of nivolumab-induced fulminant type 1 diabetes
      mellitus.

PMID- 29343653
TI  - Establishment of a Screening System to Identify Novel GATA-2 Transcriptional
      Regulators.
AB  - Hematopoietic stem cells can self-renew and differentiate into all blood cell
      types. The transcription factor GATA-2 is expressed in hematopoietic stem and
      progenitor cells and is essential for cell proliferation and differentiation.
      Heterozygous germline GATA2 mutations induce GATA-2 deficiency syndrome,
      characterized by monocytopenia, a predisposition to myelodysplasia and acute
      myeloid leukemia, and a profoundly reduced dendritic cell (DC) population, which
      is associated with increased susceptibility to viral infections. Because patients
      with GATA-2 deficiency syndrome could retain a wild-type copy of GATA-2, boosting
      residual wild-type GATA-2 activity may represent a novel therapeutic strategy for
      the disease. Here, we sought to establish a screening system to identify GATA-2
      activators using human U937 monocytic cells as a potential model of the DC
      progenitor. Enforced GATA-2 expression in U937 cells induces CD205 expression, a
      marker of DC differentiation, indicating U937 cells as a surrogate of human
      primary DC progenitors. Transient luciferase reporter assays in U937 cells
      reveals a high promoter activity of the -0.5 kb GATA-2 hematopoietic-specific
      promoter (1S promoter) fused with two tandemly connected GATA-2 +9.9 kb intronic
      enhancers. We thus established U937-derived cell lines stably expressing tandem
      +9.9 kb/-0.5 kb 1S-luciferase. Importantly, forced GATA-1 expression, a repressor
      for GATA-2 expression, in the stable clones caused significant decreases in the
      luciferase activities. In conclusion, our system represents a potential tool for
      identifying novel regulators of GATA-2, thereby contributing to the development
      of novel therapeutic approaches.

PMID- 29343654
TI  - Intestinal Epithelial Cell-specific Deletion of alpha-Mannosidase II Ameliorates
      Experimental Colitis.
AB  - Inflammatory bowel disease (IBD) is a refractory disease of the gastrointestinal
      tract that is believed to develop in genetically susceptible individuals.
      Glycosylation, a type of post-translational modification, is involved in the
      development of a wide range of diseases, including IBD, by modulating the
      function of various glycoproteins. To identify novel genes contributing to the
      development of IBD, we analyzed single nucleotide polymorphisms (SNPs) of
      glycosylation-related genes in IBD patients and identified MAN2A1, encoding alpha
      mannosidase II (alpha-MII), as a candidate gene. alpha-MII plays a crucial, but
      not exclusive, role in the maturation of N-glycans. We also observed that
      intestinal epithelial cells (IECs), which establish the first-line barrier and
      regulate gut immunity, selectively expressed alpha-MII with minimal expression of
      its isozyme, alpha-mannosidase IIx (alpha-MIIx). This led us to hypothesize that
      IEC-intrinsic alpha-MII is implicated in the pathogenesis of IBD. To test this
      hypothesis, we generated IEC-specific alpha-MII-deficient (alpha-MIIDeltaIEC)
      mice. Although alpha-MII deficiency has been shown to have a minimal effect on N
      glycan maturation in most cell types due to the compensation by alpha-MIIx,
      ablation of alpha-MII impaired the maturation of N-glycans in IECs. alpha
      MIIDeltaIEC mice were less susceptible to dextran sulfate sodium-induced colitis
      compared with control littermates. In accordance with this, neutrophil
      infiltration in the colonic mucosa was attenuated in alpha-MIIDeltaIEC mice.
      Furthermore, gene expression levels of neutrophil-attracting chemokines were
      downregulated in the colonic tissue. These results suggest that IEC-intrinsic
      alpha-MII promotes intestinal inflammation by facilitating chemokine expression.
      We propose SNPs in MAN2A1 as a novel genetic factor for IBD.Key words:
      inflammatory bowel disease, alpha-mannosidase II, intestinal epithelial cell, N
      glycosylation.

PMID- 29343655
TI  - Spatiotemporal alterations of autophagy marker LC3 in rat skin fibroblasts during
      wound healing process.
AB  - To investigate the possible implications of autophagy, one of the degradation
      pathways induced by metabolic stress, in the dynamic reconstructive process of
      wound healing, the appearance and changes of punctate structures for microtubule
      associated protein 1 light chain 3 (LC3), an autophagosome marker, were examined
      in a rat skin wound healing model. Although the ratio of LC3-II/LC3-I in Western
      blotting was not evidently changed during the wound healing process, LC3-positive
      dots were clearly observed in fibroblasts and myofibroblasts, and occasionally in
      macrophages, by immunohistofluorescence microscopy. Some of the LC3-positive dots
      were colocalized with Atg16L signal, an isolation membrane marker, and electron
      microscopy revealed the presence of typical autophagosomes in fibroblasts near
      the margin of the wound. The number of LC3-positive dots per fibroblast increased
      during the later period of the proliferation phase, and interestingly, it was
      higher in the margin than the center of the wound. It was also high in the
      periwound skin area. These results suggest that drastic functional changes in
      fibroblasts during wound healing process are accompanied by the alteration of the
      autophagy-lysosomal degradation system.

PMID- 29343656
TI  - CRISPR-Cas9-mediated generation of obese and diabetic mouse models.
AB  - Mouse models of obesity (ob/ob) and diabetes (db/db) in which the leptin (Lep)
      and leptin receptor (Lepr) genes have been mutated, respectively, have
      contributed to a better understanding of human obesity and type 2 diabetes and to
      the prevention, diagnosis, and treatment of these metabolic diseases. In this
      study, we report the first CRISPR-Cas9-induced Lep and Lepr knockout (KO) mouse
      models by co-microinjection of Cas9 mRNA and sgRNAs that specifically targeted
      Lep or Lepr in C57BL/6J embryos. Our newly established Lep and Lepr KO mouse
      models showed phenotypic disorders nearly identical to those found in ob/ob and
      db/db mice, such as an increase in body weight, hyperglycemia, and hepatic
      steatosis. Thus, Cas9-generated Lep and Lepr KO mouse lines will be easier for
      genotyping, to maintain the lines, and to use for future obesity and diabetes
      research.

PMID- 29343657
TI  - Combining Segmented Grey and White Matter Images Improves Voxel-based Morphometry
      for the Case of Dilated Lateral Ventricles.
AB  - PURPOSE: To evaluate the error in segmented tissue images and to show the
      usefulness of the brain image in voxel-based morphometry (VBM) using Statistical
      Parametric Mapping (SPM) 12 software and 3D T1-weighted magnetic resonance images
      (3D-T1WIs) processed to simulate idiopathic normal pressure hydrocephalus (iNPH).
      MATERIALS AND METHODS: VBM analysis was performed on sagittal 3D-T1WIs obtained
      in 22 healthy volunteers using a 1.5T MR scanner. Regions of interest for the
      lateral ventricles of all subjects were carefully outlined on the original 3D
      T1WIs, and two types of simulated 3D-T1WI were also prepared (non-dilated 3D-T1WI
      as normal control and dilated 3D-T1WI to simulate iNPH). All simulated 3D-T1WIs
      were segmented into gray matter, white matter, and cerebrospinal fluid images,
      and normalized to standard space. A brain image was made by adding the gray and
      white matter images. After smoothing with a 6-mm isotropic Gaussian kernel, group
      comparisons (dilated vs non-dilated) were made for gray and white matter,
      cerebrospinal fluid, and brain images using a paired t-test. RESULTS: In
      evaluation of tissue volume, estimation error was larger using gray or white
      matter images than using the brain image, and estimation errors in gray and white
      matter volume change were found for the brain surface. CONCLUSION: To our
      knowledge, this is the first VBM study to show the possibility that VBM of gray
      and white matter volume on the brain surface may be more affected by individual
      differences in the level of dilation of the lateral ventricles than by individual
      differences in gray and white matter volumes. We recommend that VBM evaluation in
      patients with iNPH should be performed using the brain image rather than the gray
      and white matter images.

PMID- 29343658
TI  - Differences in Signal Intensity and Enhancement on MR Images of the Perivascular
      Spaces in the Basal Ganglia versus Those in White Matter.
AB  - PURPOSE: To elucidate differences between the perivascular space (PVS) in the
      basal ganglia (BG) versus that found in white matter (WM) using heavily T2
      weighted FLAIR (hT2-FL) in terms of 1) signal intensity on non-contrast enhanced
      images, and 2) the degree of contrast enhancement by intravenous single dose
      administration of gadolinium based contrast agent (IV-SD-GBCA). MATERIALS AND
      METHODS: Eight healthy men and 13 patients with suspected endolymphatic hydrops
      were included. No subjects had renal insufficiency. All subjects received IV-SD
      GBCA. MR cisternography (MRC) and hT2-FL images were obtained prior to and 4 h
      after IV-SD-GBCA. The signal intensity of the PVS in the BG, subinsular WM, and
      the cerebrospinal fluid (CSF) in Ambient cistern (CSFAC) and CSF in Sylvian
      fissure (CSFSyl) was measured as well as that of the thalamus. The signal
      intensity ratio (SIR) was calculated by dividing the intensity by that of the
      thalamus. We used 5% as a threshold to determine the significance of the
      statistical test. RESULTS: In the pre-contrast scan, the SIR of the PVS in WM
      (Mean +/- standard deviation, 1.83 +/- 0.46) was significantly higher than that
      of the PVS in the BG (1.05 +/- 0.154), CSFSyl (1.03 +/- 0.15) and the CSFAC (0.97
      +/- 0.29). There was no significant difference between the SIR of the PVS in the
      BG compared to the CSFAC and CSFSyl. For the evaluation of the contrast
      enhancement effect, significant enhancement was observed in the PVS in the BG,
      the CSFAC and the CSFSyl compared to the pre-contrast scan. No significant
      contrast enhancement was observed in the PVS in WM. CONCLUSION: The signal
      intensity difference between the PVS in the BG versus WM on pre-contrast images
      suggests that the fluid composition might be different between these PVSs. The
      difference in the contrast enhancement between the PVSs in the BG versus WM
      suggests a difference in drainage function.

PMID- 29343660
TI  - MR-guided Focused Ultrasound for Uterine Fibroids: A Preliminary Study of
      Relationship between the Treatment Outcomes and Factors of MR Images Including
      Elastography.
AB  - We evaluated the value of magnetic resonance elastography (MRE) for the
      prediction of response to magnetic resonance-guided focused ultrasound (MRgFUS)
      for uterine fibroids. Eleven patients were enrolled. A fractional change of >30%
      in Symptoms Severity Score (SSS) was defined as a 'substantial symptomatic
      improvement' at 12 months after treatment. The fractional stiffness value
      reduction in the patients with a substantial improvement in SSS was significantly
      higher than that in those without (P = 0.0446).

PMID- 29343659
TI  - Cardiac MR Imaging of Hypertrophic Cardiomyopathy: Techniques, Findings, and
      Clinical Relevance.
AB  - Hypertrophic cardiomyopathy (HCM) is a relatively common myocardial genetic
      disease having a wide variety of symptoms and prognoses. The most serious
      complications of HCM are sudden cardiac death induced by ventricular arrhythmia
      or inappropriate changes in blood pressure, and heart failure. Cardiac MR imaging
      is a valuable imaging method for detecting HCM because of its accurate
      measurement of wall thickness and myocardial mass without limited view and the
      unique ability of late gadolinium enhancement (LGE) to identify myocardial
      fibrosis related to the prognosis of HCM. Tagging and T1 or T2 mapping MR imaging
      techniques have emerged as quantitative methods for the evaluation of disease
      severity. In this review, we introduce the MR imaging techniques applied to HCM
      and demonstrate the typical phenotypes and some morphological characteristics of
      HCM. In addition, we discuss the clinical relevance of MR imaging for risk
      stratification and management of HCM.

PMID- 29343661
TI  - Immobilization Technique for High-Resolution MR Imaging of the Testes.
AB  - Techniques for testis immobilization can facilitate high-resolution MR imaging
      applications for testicular diseases by assuring good positioning of the testis
      on small radiofrequency coils and reducing motion artifacts. We tested negative
      pressure suction to immobilize the testis of rats during MR image acquisitions.
      Suction pressure between -5 and -10 kPa assured good positioning, suppressed
      motion artifacts, and allowed the observation of blood vessels and seminiferous
      tubules.

PMID- 29343662
TI  - Cost-Benefit Performance Simulation of Robot-Assisted Thoracic Surgery As
      Required for Financial Viability under the 2016 Revised Reimbursement Paradigm of
      the Japanese National Health Insurance System.
AB  - PURPOSE: To discuss the cost-benefit performance (CBP) and establish a medical
      fee system for robotic-assisted thoracic surgery (RATS) under the Japanese
      National Health Insurance System (JNHIS), which is a system not yet firmly
      established. METHODS: All management steps for RATS are identical, such as
      preoperative and postoperative management. This study examines the CBP based on
      medical fees of RATS under the JNHIS introduced in 2016. RESULTS: Robotic
      assisted laparoscopic prostatectomy (RALP) and robotic-assisted partial
      nephrectomy (RAPN) now receive insurance reimbursement under the category of use
      of support devices for endoscopic surgery ($5420 and $3485, respectively). If the
      same standard amount were to be applied to RATS, institutions would need to
      perform at least 150 or 300 procedures thoracic operation per year to show a
      positive CBP ($317 per procedure as same of RALP and $130 per procedure as same
      of RAPN, respectively). CONCLUSION: Robotic surgery in some areas receives
      insurance reimbursement for its "supportive" use for endoscopic surgery as for
      RALP and RAPN. However, at present, it is necessary to perform da Vinci Surgical
      System Si (dVSi) surgery at least 150-300 times in a year in a given institution
      to prevent a deficit in income.

PMID- 29343663
TI  - The Efficacy of VATS and Intrapleural Fibrinolytic Therapy in Parapneumonic
      Empyema Treatment.
AB  - BACKGROUND: Development of multiloculation-septation is a challenging entity in
      empyema patients. In this study, it is aimed to investigate the success rates of
      videothoracoscopic deloculation (VATS-D) and intrapleural fibrinolytic (IPFib)
      application after tube thoracostomy. METHODS: The study retrospectively examined
      the patients diagnosed with empyema with multiloculation and septation between
      January 2005 and December 2014. Among these patients, the study included those
      who received VATS-D or IPFib therapy. RESULTS: VATS-D (Group 1) was applied to 54
      patients and IPFib (Group 2) was applied to 24 patients. The success of both
      procedures was evaluated considering the need of decortication in the following
      periods. In the VATS-D group, 4 (7.4%) patients required decortication via
      thoracotomy where it was 1 (4.1%) patient (p = 0.577) in the IPFib group. The
      length of hospital stay was 6.81 +/- 2.55 (4-15) days in Group 1 compared to
      14.25 +/- 6.44 (7-27) days in Group 2 (p <0.001). CONCLUSIONS: It was
      demonstrated that both of the methods applied in the study have high efficacy and
      are preferable methods based on the general conditions of patients. Additionally,
      the shorter length of hospital stays in patients received VATS-D was established
      as a significant parameter.

PMID- 29343664
TI  - The anti-inflammatory action of maropitant in a mouse model of acute
      pancreatitis.
AB  - The neurokinin 1 receptor (NK1R) plays an important role in the pathogenesis of
      acute pancreatitis (AP). Maropitant is an NK1R antagonist that is widely used as
      an antiemetic in dogs and cats. In the present study, we investigated the anti
      inflammatory action of maropitant in a mouse model of AP. AP was induced in
      BALB/c mice by intraperitoneal administration of cerulein, and maropitant was
      administered subcutaneously at a dose of 8 mg/kg. We assessed the mRNA expression
      levels of NK1R and substance P (SP) in the pancreatic tissue via real-time
      reverse transcription polymerase chain reaction. In addition, the effect of
      maropitant on plasma amylase, lipase, and interleukin-6 (IL-6) levels was
      measured in each mouse. Inflammatory cell infiltration in the pancreas was
      assessed by myeloperoxidase (MPO) staining. Our results showed that AP induction
      significantly elevated the mRNA expression of SP in the pancreatic tissue.
      Treatment with maropitant significantly lowered plasma amylase and IL-6 levels.
      In addition, treatment with maropitant inhibited the infiltration of MPO-positive
      cells in the pancreas. The present study suggests that maropitant possesses an
      anti-inflammatory activity, in addition to its antiemetic action.

PMID- 29343665
TI  - Molecular characterization of gliadins of Chinese Spring wheat in relation to
      celiac disease elicitors.
AB  - The wheat seed storage proteins gliadin and glutenin are encoded by multigenes.
      Gliadins are further classified into alpha-, gamma-, delta- and omega-gliadins.
      Genes encoding alpha-gliadins belong to a large multigene family, whose members
      are located on the homoeologous group 6 chromosomes at the Gli-2 loci. Genes
      encoding other gliadins are located on the homoeologous group 1 chromosomes at
      the Gli-1 loci. Two-dimensional polyacrylamide gel electrophoresis (2-DE) was
      used to characterize and profile the gliadins. The gliadins in aneuploid Chinese
      Spring wheat lines were then compared in this study. Gliadin proteins separated
      into 70 spots after 2-DE and a total of 10, 10 and 16 spots were encoded on
      chromosomes 6A, 6B and 6D, respectively, which suggested that they were alpha
      gliadins. Similarly, six, three and seven spots were encoded on chromosomes 1A,
      1B and 1D, respectively, which indicated that they were gamma-gliadins. Spots
      that could not be assigned to chromosomes were N-terminally sequenced and were
      all determined to be alpha-gliadins or gamma-gliadins. The 2-DE profiles showed
      that specific alpha-gliadin spots assigned to chromosome 6D were lost in
      tetrasomic chromosome 2A lines. Furthermore, western blotting against the Glia
      alpha9 peptide, an epitope for celiac disease (CD), suggested that alpha-gliadins
      harboring the CD epitope on chromosome 6D were absent in the tetrasomic
      chromosome 2A lines. Systematic analysis of alpha-gliadins using 2-DE,
      quantitative RT-PCR and genomic PCR revealed that tetrasomic 2A lines carry
      deletion of a chromosome segment at the Gli-D2 locus. This structural alteration
      at the Gli-D2 locus may provide a genetic resource in breeding programs for the
      reduction of CD immunotoxicity.

PMID- 29343666
TI  - The C-terminal extension domain of Saccharomyces cerevisiae MrpL32, a homolog of
      ribosomal protein L32, functions in trans to support mitochondrial translation.
AB  - Mitochondrial ribosomal protein L32 (MrpL32) of Saccharomyces cerevisiae is
      homologous to the bacterial L32 ribosomal protein. MrpL32 carries an N-terminal
      mitochondrion-targeting sequence (MTS) and is about 60 amino acid residues longer
      at the C-terminus. Adding to its function as a leader sequence, the MTS of MrpL32
      has been reported to regulate ribosome biogenesis through its processing by m-AAA
      protease. However, the function of the C-terminal extension (CE) remains totally
      unknown. Therefore, we constructed a series of C-terminally truncated mrpl32
      (mrpl32DeltaC) genes and expressed them in a Deltamrpl32 mutant to examine their
      function. Interestingly, some MrpL32DeltaC derivatives exhibited temperature
      sensitive (ts) growth on medium with non-fermentable carbon sources. Furthermore,
      the CE domain of MrpL32, expressed separately from MrpL32DeltaC, could rescue the
      ts phenotype of mutants by improving mitochondrial protein synthesis.

PMID- 29343667
TI  - Genotypic effects on sugar and by-products of liquid hydrolysates and on
      saccharification of acid-insoluble residues from wheat straw.
AB  - Wheat straw is one of the major attractive resources for low-cost raw materials
      for renewable energy, biofuels and biochemicals. However, like other sources of
      lignocellulosic biomass, straw is a heterogeneous material due to its mixed
      origin from different tissue and cell types. Here, to examine the genotypic
      effects on biorefinery usage of wheat straw, straw obtained from different wheat
      cultivars and experimental lines was pretreated with dilute acid. Significant
      differences between cultivars were observed in the concentrations of glucose and
      toxic by-products of the liquid hydrolysates. A higher content of xylose than
      glucose was found in liquid hydrolysates from wheat straw, and the xylose content
      appeared to be affected by both environmental and genetic factors. Analysis using
      chromosome substitution lines of the common wheat cultivar Chinese Spring showed
      that chromosomes 2A and 3A from other wheat cultivars, Hope and Timstein,
      significantly increased the xylose content. However, no significant relationship
      was observed between the liquid hydrolysate xylose content and the glucose
      content obtained from enzymatic saccharification of the acid-insoluble residue.
      These results highlight the potential of wheat breeding to improve biomass
      related traits in wheat straw.

PMID- 29343668
TI  - Configuration of the sugar head of glycolipids in thylakoid membranes.
AB  - Glycolipids constitute the majority of membrane components in oxygenic
      photosynthetic organisms, whereas they are minor lipids in other organisms. In
      cyanobacteria, three glycolipids comprise ~90 mol% of the total lipids in
      thylakoid membranes, where photosynthetic electron transport occurs. Among these
      glycolipids, 80 mol% are galactolipids (monogalactosyldiacylglycerol and
      digalactosyldiacylglycerol). Galactolipids are well conserved in oxygenic
      photosynthetic organisms and are believed to be essential for the integrity of
      the membrane system. It remains unclear, however, which part(s) of the
      galactolipid structure is the key factor for their function, e.g., the sugar
      moiety and/or the anomeric configuration. To address this issue, several
      bacterial membrane glycolipid synthase genes have been introduced into
      cyanobacteria to test for complementation of knocked-out genes involved in
      galactolipid biosynthesis. In this review, we summarize recent advances in the
      analyses of sugar species and configurations of glycolipids heterologously
      synthesized in the thylakoid membrane and discuss their functional importance.

PMID- 29343669
TI  - Direct interaction between VRN1 protein and the promoter region of the wheat FT
      gene.
AB  - The wheat florigen gene Wheat FLOWERING LOCUS T (WFT, which is identical to VRN3)
      is an integrator of the vernalization, photoperiod and autonomous pathways in
      wheat flowering. Many studies have indicated that VERNALIZATION 1 (VRN1) directly
      or indirectly up-regulates WFT expression in leaves. VRN1 encodes an
      APETALA1/FRUITFULL-like MADS box transcription factor that is up-regulated by
      vernalization and aging, leading to promotion of flowering. In this study, the
      VRN1 protein was expressed as a His-Tag fusion protein in Escherichia coli and
      used in an electrophoretic mobility shift assay (EMSA). The results from the EMSA
      indicated that the VRN1 protein directly binds to the CArG-box in the promoter
      region of WFT, suggesting the direct up-regulation of WFT by VRN1 in the leaves
      of wheat plants.

PMID- 29343670
TI  - Anti-sigma factor-mediated cell surface stress responses in Bacillus subtilis.
AB  - Proteins belonging to the sigma factor family in eubacteria initiate
      transcription by associating with RNA polymerase. A subfamily, the
      extracytoplasmic function (ECF) sigma factors, which form a widely distributed
      bacterial signal transduction system comprising a sigma factor and a cognate
      membrane-embedded anti-sigma factor, regulates genes in response to stressors
      that threaten cell envelope integrity including the cell wall and membrane. The
      Gram-positive soil bacterium Bacillus subtilis provides a valuable model for
      investigation of the ECF sigma factors. This review focuses on the function and
      regulation of ECF sigma factors in B. subtilis, in which anti-sigma factors play
      a role in connecting an external stimulus with gene regulation. As representative
      examples, the regulon and regulatory mechanism of sigmaW are closely associated
      with membrane-active stressors, whereas sigmaM is strongly induced by conditions
      that impair peptidoglycan synthesis. These studies demonstrate that the
      mechanisms of ECF-dependent signaling are divergent and constitute a multi
      layered hierarchy, and provide useful insights into the elucidation of unknown
      mechanisms related to ECF sigma factors.

PMID- 29343672
TI  - Applying the Seattle Heart Failure Model in the Office Setting in the Era of
      Electronic Medical Records.
AB  - BACKGROUND: Prediction models such as the Seattle Heart Failure Model (SHFM) can
      help guide management of heart failure (HF) patients, but the SHFM has not been
      validated in the office environment. This retrospective cohort study assessed the
      predictive performance of the SHFM among patients with new or pre-existing HF in
      the context of an office visit.Methods and Results:SHFM elements were ascertained
      through electronic medical records at an office visit. The primary outcome was
      all-cause mortality. A "warranty period" for the baseline SHFM risk estimate was
      sought by examining predictive performance over time through a series of landmark
      analyses. Discrimination and calibration were estimated according to the proposed
      warranty period. Low- and high-risk thresholds were proposed based on the
      distribution of SHFM estimates. Among 26,851 HF patients, 14,380 (54%) died over
      a mean 4.7-year follow-up period. The SHFM lost predictive performance over time,
      with C=0.69 and C<0.65 within 3 and beyond 12 months from baseline respectively.
      The diminishing predictive value was attributed to modifiable SHFM elements.
      Discrimination (C=0.66) and calibration for 12-month mortality were acceptable. A
      low-risk threshold of ~5% mortality risk within 12 months reflects the 10% of HF
      patients in the office setting with the lowest risk. CONCLUSIONS: The SHFM has
      utility in the office environment.

PMID- 29343671
TI  - Development of microsatellite markers for the endangered orchid Calanthe izu
      insularis (Orchidaceae).
AB  - Microsatellite markers were developed for the endangered orchid Calanthe izu
      insularis (Orchidaceae). This species is unique to the Izu Islands in Japan.
      Unfortunately, its population size has decreased because of excessive collection
      for horticultural purposes. In addition, although natural hybridization between
      C. izu-insularis and C. discolor var. discolor has been reported, morphological
      differences between C. izu-insularis and the hybridized individuals remain
      unclear. Using next-generation sequencing, 11 polymorphic microsatellite markers
      were developed. All developed markers could amplify C. aristulifera and nine
      markers could amplify C. d. var. discolor, two other orchid species that are also
      endangered in Japan. The number of alleles and expected heterozygosity at each
      locus were 1-6 (mean, 2.35) and 0.00-0.79 (mean, 0.30), respectively. These
      microsatellite markers will help conservation geneticists in their investigation
      of the proportion of pure C. izu-insularis individuals in the Izu Islands.

PMID- 29343673
TI  - Transcutaneous Exercise Oximetry for Patients With Claudication - A Retrospective
      Review of Approximately 5,000 Consecutive Tests Over 15 Years.
AB  - BACKGROUND: Exercise transcutaneous oximetry (Ex-tcPO2) is used to argue for the
      vascular origin of lower limb pain, especially at the proximal level, where the
      diagnosis of peripheral artery disease can be difficult. This study analyzed the
      principal indications, mean results, and limitations of Ex-tcPO2, as well as the
      relationship between the annual number of Ex-tcPO2 tests and internal iliac
      artery (IIA) revascularizations.Methods and Results:Data from our first 15 years'
      experience (3,631 patients, 5,080 tests) with Ex-tcPO2 were analyzed
      retrospectively using the minimal value of the decrease from rest of oxygen
      pressure (DROPmin). We had 99.7% of expected DROPminresults. The proportion of
      tests showing isolated proximal unilateral or bilateral ischemia ranged from ~5%
      to ~20%. A gradual increase with time was observed in both the annual number of
      Ex-tcPO2 tests (from 0 to ~500 per year) and the annual number of IIA
      revascularizations performed (from 0 up to 18 per year). At least 85% of patients
      (77/91) showed function improvement after IIA revascularization. CONCLUSIONS: Ex
      tcPO2 (using DROPmin) provides an objective argument for exercise-induced
      ischemia, bilaterally at the distal and/or proximal level. Using Ex-tcPO2 has
      improved our diagnostic performance and markedly changed our therapeutic
      decisions, specifically for proximal claudication. The increased number of Ex
      tcPO2 tests is associated with an increased number of IIA revascularizations,
      although a causal relationship was not proven.

PMID- 29343674
TI  - A Spontaneous Abdominal Aortic Pseudoaneurysm Treated with N-butyl Cyanoacrylate
      and Coil Embolization: A Case Report.
AB  - Pseudoaneurysms are vascular spaces vulnerable to pressure, and expansion or
      rupture of these spaces may occur during embolization. Here, we describe the case
      of a transcatheter embolization of a spontaneous aortic pseudoaneurysm, which
      showed gradual expansion during n-butyl cyanoacrylate embolization. This
      pseudoaneurysm was successfully embolized with an adjuvant coil.

PMID- 29343676
TI  - Editorial Statistics and Best Reviewers Award for 2017.

PMID- 29343675
TI  - Diagnostic Accuracy of Quantitative Flow Ratio for Assessing Myocardial Ischemia
      in Prior Myocardial Infarction.
AB  - BACKGROUND: A novel index of the functional severity of coronary stenosis,
      quantitative flow ratio (QFR), may not consider the amount of viable myocardium
      in prior myocardial infarction (MI) because QFR is calculated from 3D
      quantitative coronary angiography.Methods and Results:We analyzed QFR (fixed-flow
      QFR [fQFR] and contrast-flow QFR [cQFR]) and fractional flow reserve (FFR) in
      prior-MI-related coronary arteries (n=75) and non-prior-MI-related coronary
      arteries (n=75). Both fQFR and cQFR directly correlated with FFR in the prior-MI
      related coronary arteries (fQFR: r=0.84, P<0.001; and cQFR: r=0.88, P<0.001) and
      the non-prior-MI-related coronary arteries (fQFR: r=0.91, P<0.001; and cQFR:
      r=0.94, P<0.001). fQFR was significantly smaller than FFR in the prior-MI-related
      coronary arteries (0.73+/-0.14 vs. 0.79+/-0.11, P=0.002), but there was no
      significant difference between fQFR and FFR in the non-prior-MI-related coronary
      arteries. The value of cQFR minus FFR was significantly lower in the prior-MI
      related coronary arteries compared with the non-prior-MI-related coronary
      arteries (-0.02+/-0.06 vs. 0.00+/-0.04, P=0.010). The diagnostic accuracy of fQFR
      <=0.8 and cQFR <=0.8 for predicting FFR <=0.80 was numerically lower in the prior
      MI-related coronary arteries compared with the non-prior-MI-related coronary
      arteries (fQFR: 77% vs. 87%; and cQFR: 87% vs. 92%). CONCLUSIONS: When FFR is
      used as the gold standard, the accuracy of QFR for assessing the functional
      severity of coronary stenosis might be reduced in the prior-MI-related coronary
      arteries compared with non-prior-MI-related coronary arteries.

PMID- 29343678
TI  - Impact of Anemia on Left Ventricular Reverse Remodeling in Response to
      Carvedilol.

PMID- 29343677
TI  - Prognostic Factors in Glioblastoma: Is There a Role for Epilepsy?
AB  - The prognostic relevance of epilepsy at glioblastoma (GBMs) onset is still under
      debate. In this study, we analyzed the value of epilepsy and other prognostic
      factors on GBMs survival. We retrospectively analyzed the clinical, radiological,
      surgical and histological data in 139 GBMs. Seizures were the presenting symptoms
      in 50 patients out of 139 (35.9%). 123 patients (88%) were treated with
      craniotomy and tumor resection while 16 (12%) with biopsy. The median overall
      survival was 9.9 months from surgery. At univariable Cox regression, the factors
      that significantly improved survival were age less than 65 years (P = 0.0015),
      focal without impairment of consciousness seizures at presentation (P = 0.043),
      complete surgical resection (P < 0.001), pre-operative Karnofsky performance
      status (KPS) > 70 (P = 0.015), frontal location (P < 0.001), radiotherapy (XRT)
      plus concomitant and adjuvant TMZ (P < 0.001). A multivariable Cox regression
      showed that the complete surgical resection (P < 0.0001), age less than 65 years
      (P = 0.008), frontal location (P = 0.0001) and XRT adjuvant temozolomide (TMZ) (P
      < 0.0001) were independent factors on longer survival. In our series epilepsy at
      presentation is not an independent prognostic factor for longer survival in GBM
      patients. Only in the subgroup of patients with focal seizures without impairment
      of consciousness, epilepsy was associated with an increased significant overall
      survival at univariate analysis (P = 0.043). Main independent factors for
      relatively favorable GBMs outcome are complete tumor resection plus combined XRT
      TMZ, frontal location and patient age below 65 years old.

PMID- 29343679
TI  - Ramsay Hunt Syndrome with Multiple Cranial Neuropathy in an Human
      Immunodeficiency Virus (HIV) Patient.
AB  - BACKGROUND Ramsay Hunt syndrome is a rare otologic complication resulting from
      varicella zoster virus reactivation that can present with a myriad of clinical
      presentations. Most common being triad of ear pain, vesicles at auricle, and ear
      canal with same side facial palsy. CASE REPORT We report a case of a 29-year-old
      male with a human immunodeficiency virus (HIV) infection who presented with left
      facial palsy, vesicles, pain in the left ear, dysphagia, dizziness, and headache
      resulting from multiple cranial nerves involvement such as cranial nerve V, VII,
      VIII, IX, and X. CONCLUSIONS This case report raises awareness among general
      practitioners to investigate for Ramsay Hunt syndrome in HIV patients presenting
      with ear pain with a thorough neurological exam and emphasize on the interplay of
      different specialties in managing these patients.

PMID- 29343680
TI  - Martrilin-3 (MATN3) Overexpression in Gastric Adenocarcinoma and its Prognostic
      Significance.
AB  - BACKGROUND The aim of this study was to investigate the expression level of
      martrilin-3 (MATN3) in patients with gastric adenocarcinoma (GAC) and to
      investigate the prognostic significance of MATN3. MATERIAL AND METHODS Gene
      Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) data were used to
      predict the expression and prognostic value of MATN3 mRNA in GAC patients.
      Seventy-six GAC patients had GAC tissue samples and paired adjacent normal tissue
      samples collected retrospectively to examine the MATN3 protein expression level
      by immunohistochemical staining. Furthermore, Kaplan-Meier univariate and Cox
      multivariate analyses were used to verify the correlation between MATN3
      expression and clinicopathological parameters of GAC patients and the prognostic
      significance of MATN3. RESULTS The GEO and TCGA data predicted that MATN3 mRNA
      levels were significantly higher in GAC tissue compared to normal tissue (all
      p<0.05). Further survival analyses showed that GAC patients with high mRNA
      expression of MATN3 had significantly lower disease-free survival (DFS) and
      overall survival (OS) time than those with low mRNA expression of MATN3 (all
      p<0.05). Subsequent immunohistochemical staining results confirmed that the MATN3
      protein levels in GAC tissues were highly expressed (p=0.000) compared to normal
      tissues. In addition, GAC patients with high protein expression of MATN3 had
      remarkably decreased OS compared to patients with low protein expression of MATN3
      (p=0.000). Univariate and multivariate survival analyses revealed that MATN3 high
      expression could be used as an independent predictor of poor prognosis in GAC
      patients (all p=0.000). CONCLUSIONS This study confirmed that MATN3 protein was
      highly expressed in GAC patients, and MATN3 overexpression could be used as an
      independent predictor of poor prognosis in GAC patients.

PMID- 29343681
TI  - Oral health in China: from vision to action.
AB  - Chinese president Xi Jinping made clear at the National Health and Wellness
      Conference that health is the prerequisite for people's all-around development
      and a precondition for the sustainable development of China. Oral health is an
      indispensable component of overall health in humans. However, the long neglect of
      oral health in overall health agendas has made oral diseases an increasing
      concern. With this perspective, we described the global challenges of oral
      diseases, with an emphasis on the challenges faced by China. We also described
      and analyzed the recently released health policies of the Chinese government,
      which aim to guide mid-term and long-term oral health promotion in China. More
      importantly, we called for specific actions to fulfill the larger goal of oral
      health for the nation. The implementation of primordial prevention efforts
      against oral diseases, the integration of oral health into the promotion of
      overall health, and the management of oral diseases in conjunction with other
      chronic non-communicable diseases with shared risk factors were highly
      recommended. In addition, we suggested the reform of standard clinical residency
      training, the development of domestic manufacturing of dental equipment and
      materials, the revitalization traditional Chinese medicine for the prevention and
      treatment of oral diseases, and integration of oral health promotion into the
      Belt and Road Initiative. We look forward to seeing a joint effort from all
      aspects of the society to fulfill the goal of Healthy China 2030 and ensure the
      oral health of the nation.

PMID- 29343682
TI  - Intermittent C1-Inhibitor Deficiency Associated with Recessive Inheritance:
      Functional and Structural Insight.
AB  - C1-inhibitor is a serine protease inhibitor (serpin) controlling complement and
      contact system activation. Gene mutations result in reduced C1-inhibitor
      functional plasma level causing hereditary angioedema, a life-threatening
      disorder. Despite a stable defect, the clinical expression of hereditary
      angioedema is unpredictable, and the molecular mechanism underlying this
      variability remains undisclosed. Here we report functional and structural studies
      on the Arg378Cys C1-inhibitor mutant found in a patient presenting reduced C1
      inhibitor levels, episodically undergoing normalization. Expression studies
      resulted in a drop in mutant C1-innhibitor secretion compared to wild-type.
      Notwithstanding, the purified proteins had similar features. Thermal denaturation
      experiments showed a comparable denaturation profile, but the mutant thermal
      stability decays when tested in conditions reproducing intracellular crowding.Our
      findings suggest that once correctly folded, the Arg378Cys C1-inhibitor is
      secreted as an active, although quite unstable, monomer. However, it could bear a
      folding defect, occasionally promoting protein oligomerization and interfering
      with the secretion process, thus accounting for its plasma level variability.
      This defect is exacerbated by the nature of the mutation since the acquired
      cysteine leads to the formation of non-functional homodimers through inter
      molecular disulphide bonding. All the proposed phenomena could be modulated by
      specific environmental conditions, rendering this mutant exceptionally vulnerable
      to mild stress.

PMID- 29343683
TI  - Hypoxia-inducible factor-1alpha is a critical transcription factor for IL-10
      producing B cells in autoimmune disease.
AB  - Hypoxia-inducible factors (HIFs) are key elements for controlling immune cell
      metabolism and functions. While HIFs are known to be involved in T cells and
      macrophages activation, their functions in B lymphocytes are poorly defined.
      Here, we show that hypoxia-inducible factor-1alpha (HIF-1alpha) contributes to IL
      10 production by B cells. HIF-1alpha regulates IL-10 expression, and HIF-1alpha
      dependent glycolysis facilitates CD1dhiCD5+ B cells expansion. Mice with B cell
      specific deletion of Hif1a have reduced number of IL-10-producing B cells, which
      result in exacerbated collagen-induced arthritis and experimental autoimmune
      encephalomyelitis. Wild-type CD1dhiCD5+ B cells, but not Hif1a-deficient
      CD1dhiCD5+ B cells, protect recipient mice from autoimmune disease, while the
      protective function of Hif1a-deficient CD1dhiCD5+ B cells is restored when their
      defective IL-10 expression is genetically corrected. Taken together, this study
      demonstrates the key function of the hypoxia-associated transcription factor HIF
      1alpha in driving IL-10 expression in CD1dhiCD5+ B cells, and in controlling
      their protective activity in autoimmune disease.

PMID- 29343684
TI  - MAIT cell clonal expansion and TCR repertoire shaping in human volunteers
      challenged with Salmonella Paratyphi A.
AB  - Mucosal-associated invariant T (MAIT) cells are innate-like T cells that can
      detect bacteria-derived metabolites presented on MR1. Here we show, using a
      controlled infection of humans with live Salmonella enterica serovar Paratyphi A,
      that MAIT cells are activated during infection, an effect maintained even after
      antibiotic treatment. At the peak of infection MAIT cell T-cell receptor
      (TCR)beta clonotypes that are over-represented prior to infection transiently
      contract. Select MAIT cell TCRbeta clonotypes that expand after infection have
      stronger TCR-dependent activation than do contracted clonotypes. Our results
      demonstrate that host exposure to antigen may drive clonal expansion of MAIT
      cells with increased functional avidity, suggesting a role for specific
      vaccination strategies to increase the frequency and potency of MAIT cells to
      optimize effector function.

PMID- 29343685
TI  - The protective role of DOT1L in UV-induced melanomagenesis.
AB  - The DOT1L histone H3 lysine 79 (H3K79) methyltransferase plays an oncogenic role
      in MLL-rearranged leukemogenesis. Here, we demonstrate that, in contrast to MLL
      rearranged leukemia, DOT1L plays a protective role in ultraviolet radiation (UVR)
      induced melanoma development. Specifically, the DOT1L gene is located in a
      frequently deleted region and undergoes somatic mutation in human melanoma.
      Specific mutations functionally compromise DOT1L methyltransferase enzyme
      activity leading to reduced H3K79 methylation. Importantly, in the absence of
      DOT1L, UVR-induced DNA damage is inefficiently repaired, so that DOT1L loss
      promotes melanoma development in mice after exposure to UVR. Mechanistically,
      DOT1L facilitates DNA damage repair, with DOT1L-methylated H3K79 involvement in
      binding and recruiting XPC to the DNA damage site for nucleotide excision repair
      (NER). This study indicates that DOT1L plays a protective role in UVR-induced
      melanomagenesis.

PMID- 29343686
TI  - Human brain patterns underlying vigilant attention: impact of sleep debt,
      circadian phase and attentional engagement.
AB  - Sleepiness and cognitive function vary over the 24-h day due to circadian and
      sleep-wake-dependent mechanisms. However, the underlying cerebral hallmarks
      associated with these variations remain to be fully established. Using functional
      magnetic resonance imaging (fMRI), we investigated brain responses associated
      with circadian and homeostatic sleep-wake-driven dynamics of subjective
      sleepiness throughout day and night. Healthy volunteers regularly performed a
      psychomotor vigilance task (PVT) in the MR-scanner during a 40-h sleep
      deprivation (high sleep pressure) and a 40-h multiple nap protocol (low sleep
      pressure). When sleep deprived, arousal-promoting thalamic activation during
      optimal PVT performance paralleled the time course of subjective sleepiness with
      peaks at night and troughs on the subsequent day. Conversely, task-related
      cortical activation decreased when sleepiness increased as a consequence of
      higher sleep debt. Under low sleep pressure, we did not observe any significant
      temporal association between PVT-related brain activation and subjective
      sleepiness. Thus, a circadian modulation in brain correlates of vigilant
      attention was only detectable under high sleep pressure conditions. Our data
      indicate that circadian and sleep homeostatic processes impact on vigilant
      attention via specific mechanisms; mirrored in a decline of cortical resources
      under high sleep pressure, opposed by a subcortical "rescuing" at adverse
      circadian times.

PMID- 29343687
TI  - Mechanically-sensitive miRNAs bias human mesenchymal stem cell fate via mTOR
      signalling.
AB  - Mechanotransduction is a strong driver of mesenchymal stem cell (MSC) fate. In
      vitro, variations in matrix mechanics invoke changes in MSC proliferation,
      migration and differentiation. However, when incorporating MSCs within
      injectable, inherently soft hydrogels, this dominance over MSC response
      substantially limits our ability to couple the ease of application of hydrogels
      with efficiently directed MSC differentiation, especially in the case of bone
      generation. Here, we identify differential miRNA expression in response to
      varying hydrogel stiffness and RhoA activity. We show that modulation of miR-100
      5p and miR-143-3p can be used to bias MSC fate and provide mechanistic insight by
      demonstrating convergence on mTOR signalling. By modulating these
      mechanosensitive miRNAs, we can enhance osteogenesis in a soft 3D hydrogel. The
      outcomes of this study provide new understanding of the mechanisms regulating MSC
      mechanotransduction and differentiation, but also a novel strategy with which to
      drive MSC fate and significantly impact MSC-based tissue-engineering
      applications.

PMID- 29343688
TI  - Wee1 inhibitor MK1775 sensitizes KRAS mutated NSCLC cells to sorafenib.
AB  - Non-Small-Cell Lung Cancer (NSCLC) is a poorly chemosensitive tumor and targeted
      therapies are only used for about 15% of patients where a specific driving and
      druggable lesion is observed (EGFR, ALK, ROS). KRAS is one of the most frequently
      mutated genes in NSCLC and patients harboring these mutations do not benefit from
      specific treatments. Sorafenib, a multi-target tyrosine kinase inhibitor, was
      proposed as a potentially active drug in KRAS-mutated NSCLC patients, but
      clinical trials results were not conclusive. Here we show that the NSCLC cells'
      response to sorafenib depends on the type of KRAS mutation. KRAS G12V cells
      respond less to sorafenib than the wild-type counterpart, in vitro and in vivo.
      To overcome this resistance, we used high-throughput screening with a siRNA
      library directed against 719 human kinases, and Wee1 was selected as a sorafenib
      response modulator. Inhibition of Wee1 by its specific inhibitor MK1775 in
      combination with sorafenib restored the KRAS mutated cells' response to the multi
      target tyrosine kinase inhibitor. This combination of the Wee1 inhibitor with
      sorafenib, if confirmed in models with different genetic backgrounds, might be
      worth investigating further as a new strategy for KRAS mutated NSCLC.

PMID- 29343689
TI  - A novel alpha-conopeptide Eu1.6 inhibits N-type (CaV2.2) calcium channels and
      exhibits potent analgesic activity.
AB  - We here describe a novel alpha-conopeptide, Eu1.6 from Conus eburneus, which
      exhibits strong anti-nociceptive activity by an unexpected mechanism of action.
      Unlike other alpha-conopeptides that largely target nicotinic acetylcholine
      receptors (nAChRs), Eu1.6 displayed only weak inhibitory activity at the
      alpha3beta4 and alpha7 nAChR subtypes and TTX-resistant sodium channels, and no
      activity at TTX-sensitive sodium channels in rat dorsal root ganglion (DRG)
      neurons, or opiate receptors, VR1, KCNQ1, L- and T-type calcium channels
      expressed in HEK293 cells. However, Eu1.6 inhibited high voltage-activated N-type
      calcium channel currents in isolated mouse DRG neurons which was independent of
      GABAB receptor activation. In HEK293 cells expressing CaV2.2 channels alone,
      Eu1.6 reversibly inhibited depolarization-activated Ba2+ currents in a voltage-
      and state-dependent manner. Inhibition of CaV2.2 by Eu1.6 was concentration
      dependent (IC50 ~1 nM). Significantly, systemic administration of Eu1.6 at doses
      of 2.5-5.0 MUg/kg exhibited potent analgesic activities in rat partial sciatic
      nerve injury and chronic constriction injury pain models. Furthermore, Eu1.6 had
      no significant side-effect on spontaneous locomotor activity, cardiac and
      respiratory function, and drug dependence in mice. These findings suggest alpha
      conopeptide Eu1.6 is a potent analgesic for the treatment of neuropathic and
      chronic pain and opens a novel option for future analgesic drug design.

PMID- 29343691
TI  - Use of nanoparticle concentration as a tool to understand the structural
      properties of colloids.
AB  - Elucidation of the structural properties of colloids is paramount for a
      successful formulation. However, the intrinsic dynamism of colloidal systems
      makes their characterization a difficult task and, in particular, there is a lack
      of physicochemical techniques that can be correlated to their biological
      performance. Nanoparticle tracking analysis (NTA) allows measurements of size
      distribution and nanoparticle concentration in real time. Its analysis over time
      also enables the early detection of physical instability in the systems not
      assessed by subtle changes in size distribution. Nanoparticle concentration is a
      parameter with the potential to bridge the gap between in vitro characterization
      and biological performance of colloids, and therefore should be monitored in
      stability studies of formulations. To demonstrate this, we have followed two
      systems: extruded liposomes exposed to increasing CHCl3 concentrations, and solid
      lipid nanoparticles prepared with decreasing amounts of poloxamer 188. NTA and
      dynamic light scattering (DLS) were used to monitor changes in nanoparticle
      number and size, and to estimate the number of lipid components per particle. The
      results revealed a strong negative correlation between particle size (determined
      by DLS) and concentration (assessed by NTA) in diluted samples, which should be
      adopted to monitor nanocolloidal stability, especially in drug delivery.

PMID- 29343690
TI  - Experimental infection of cattle with Mycobacterium tuberculosis isolates shows
      the attenuation of the human tubercle bacillus for cattle.
AB  - The Mycobacterium tuberculosis complex (MTBC) is the collective term given to the
      group of bacteria that cause tuberculosis (TB) in mammals. It has been reported
      that M. tuberculosis H37Rv, a standard reference MTBC strain, is attenuated in
      cattle compared to Mycobacterium bovis. However, as M. tuberculosis H37Rv was
      isolated in the early 1930s, and genetic variants are known to exist, we sought
      to revisit this question of attenuation of M. tuberculosis for cattle by
      performing a bovine experimental infection with a recent M. tuberculosis isolate.
      Here we report infection of cattle using M. bovis AF2122/97, M. tuberculosis
      H37Rv, and M. tuberculosis BTB1558, the latter isolated in 2008 during a TB
      surveillance project in Ethiopian cattle. We show that both M. tuberculosis
      strains caused reduced gross pathology and histopathology in cattle compared to
      M. bovis. Using M. tuberculosis H37Rv and M. bovis AF2122/97 as the extremes in
      terms of infection outcome, we used RNA-Seq analysis to explore differences in
      the peripheral response to infection as a route to identify biomarkers of
      progressive disease in contrast to a more quiescent, latent infection. Our work
      shows the attenuation of M. tuberculosis strains for cattle, and emphasizes the
      potential of the bovine model as a 'One Health' approach to inform human TB
      biomarker development and post-exposure vaccine development.

PMID- 29343692
TI  - Symmetric Decomposition of Asymmetric Games.
AB  - We introduce new theoretical insights into two-population asymmetric games
      allowing for an elegant symmetric decomposition into two single population
      symmetric games. Specifically, we show how an asymmetric bimatrix game (A,B) can
      be decomposed into its symmetric counterparts by envisioning and investigating
      the payoff tables (A and B) that constitute the asymmetric game, as two
      independent, single population, symmetric games. We reveal several surprising
      formal relationships between an asymmetric two-population game and its symmetric
      single population counterparts, which facilitate a convenient analysis of the
      original asymmetric game due to the dimensionality reduction of the
      decomposition. The main finding reveals that if (x,y) is a Nash equilibrium of an
      asymmetric game (A,B), this implies that y is a Nash equilibrium of the symmetric
      counterpart game determined by payoff table A, and x is a Nash equilibrium of the
      symmetric counterpart game determined by payoff table B. Also the reverse holds
      and combinations of Nash equilibria of the counterpart games form Nash equilibria
      of the asymmetric game. We illustrate how these formal relationships aid in
      identifying and analysing the Nash structure of asymmetric games, by examining
      the evolutionary dynamics of the simpler counterpart games in several canonical
      examples.

PMID- 29343693
TI  - Phantom Acupuncture Induces Placebo Credibility and Vicarious Sensations: A
      Parallel fMRI Study of Low Back Pain Patients.
AB  - Although acupuncture is an effective therapeutic intervention for pain reduction,
      the exact difference between real and sham acupuncture has not been clearly
      understood because a somatosensory tactile component is commonly included in the
      existing sham acupuncture protocols. In an event-related fMRI experiment, we
      implemented a novel form of sham acupuncture, phantom acupuncture, that
      reproduces the acupuncture needling procedure without somatosensory tactile
      stimulation while maintaining the credibility of the acupuncture treatment
      context. Fifty-six non-specific low back pain patients received either real
      (REAL) or phantom (PHNT) acupuncture stimulation in a parallel group study. The
      REAL group exhibited greater activation in the posterior insula and anterior
      cingulate cortex, reflecting the needling-specific components of acupuncture. We
      demonstrated that PHNT could be delivered credibly. Interestingly, the PHNT
      credible group exhibited bilateral activation in SI/SII and also reported
      vicarious acupuncture sensations without needling stimulation. The PHNT group
      showed greater activation in the bilateral dorsolateral/ventrolateral prefrontal
      cortex (dlPFC/vlPFC). Moreover, the PHNT group exhibited significant pain
      reduction, with a significant correlation between the subjective fMRI signal in
      the right dlPFC/vlPFC and a score assessing belief in acupuncture effectiveness.
      These results support an expectation-related placebo analgesic effect on
      subjective pain intensity ratings, possibly mediated by right prefrontal cortex
      activity.

PMID- 29343694
TI  - Sertraline, Paroxetine, and Chlorpromazine Are Rapidly Acting Anthelmintic Drugs
      Capable of Clinical Repurposing.
AB  - Parasitic helminths infect over 1 billion people worldwide, while current
      treatments rely on a limited arsenal of drugs. To expedite drug discovery, we
      screened a small-molecule library of compounds with histories of use in human
      clinical trials for anthelmintic activity against the soil nematode
      Caenorhabditis elegans. From this screen, we found that the neuromodulatory drugs
      sertraline, paroxetine, and chlorpromazine kill C. elegans at multiple life
      stages including embryos, developing larvae and gravid adults. These drugs act
      rapidly to inhibit C. elegans feeding within minutes of exposure. Sertraline,
      paroxetine, and chlorpromazine also decrease motility of adult Trichuris muris
      whipworms, prevent hatching and development of Ancylostoma caninum hookworms and
      kill Schistosoma mansoni flatworms, three widely divergent parasitic helminth
      species. C. elegans mutants with resistance to known anthelmintic drugs such as
      ivermectin are equally or more susceptible to these three drugs, suggesting that
      they may act on novel targets to kill worms. Sertraline, paroxetine, and
      chlorpromazine have long histories of use clinically as antidepressant or
      antipsychotic medicines. They may represent new classes of anthelmintic drug that
      could be used in combination with existing front-line drugs to boost
      effectiveness of anti-parasite treatment as well as offset the development of
      parasite drug resistance.

PMID- 29343695
TI  - Altered pattern of monocyte differentiation and monocyte-derived TGF-beta1 in
      severe asthma.
AB  - CD14+ monocytes contain precursors for macrophages and fibrocytes, known to be
      involved in regulating airway remodeling in human asthma and distinguishable by
      the PM-2K marker. We sought to identify circulating subsets of PM-2K+ macrophage
      like cells and evaluate their relationships to lung function, severity and
      control status. Circulating PM-2K+ macrophage-like cells and fibrocytes could be
      identified and distinguished between normal individuals (N = 152) and asthmatic
      subjects (N = 133) using multi-parametric flow cytometry. PM-2K+ macrophage-like
      cells were found to be significantly lower in asthmatic subjects, particularly
      noted for the CD14-PM-2K+ subset and PM-2K+CCR7-CD86+ cells in subjects with poor
      lung function (FEV%/FVC% < 80%) as compared to those of normal subjects and
      asthmatics with normal lung function, whereas the frequency of fibrocytes was
      higher in asthmatics and the CCR7-CD86+ subset distribution was significantly
      different in subjects with varying severity. Moreover, exogenous transforming
      growth factor beta 1 (TGF-beta1) was found to inhibit the generation of PM-2K+
      macrophage-like cells, but promote the growth of fibrocytes, from CD14+
      monocytes, and monocyte-derived TGF-beta1 was found to correlate with the lung
      function, severity and control status in asthmatic patients. Collectively,
      aberrant differentiation of monocytes into PM-2K+ macrophage-like cell subsets
      and fibrocytes, together with increased monocyte-derived TGF-beta1, characterized
      patients with severe asthma.

PMID- 29343696
TI  - Decoupled in-plane Dipole Resonance Modulated Colorimetric Assay-Based Optical
      Ruler for Ultra-Trace Gold (Au) Detection.
AB  - Decoupling of different plasmon resonance modes (in-plane, and out-of-plane
      dipole and quadrupole resonances) by tuning nanoparticle's size and shape offers
      a new field of plasmonics as colorimetric assay-based optical-ruler for ultra
      trace sensing. Driven by its low cost, easy to perform and efficient way to
      measure trace level (up to 30 ppt in presence of common mining elements in
      natural gold ore) abundance, this study develops a highly selective and
      ultrasensitive turn-on colorimetric sensor to detect gold-ion from environmental
      samples. Different level of gold-ion tracer makes size variable spherical- and
      disc-shaped silver nanoparticles when added to a 'growth solution' which results
      decoupling of in-plane dipole resonance from in-plane quadrupole and out-of-plane
      dipole resonances with a wide range of in-plane dipole plasmon tunability to
      generate different colors. This color-coded sensing of gold-ion shows high
      selectivity and ultrasensitivity over other metal ions in the ppt level with an
      impurity aberration limit of 1 ppm. A plausible explanation explains the possible
      role of catalytic gold-ion to initiate unfavorable silver ion (Ag+) reduction by
      ascorbic acid to generate silver nanoparticles. Proposed technology has been
      applied in real mining sample (Bugunda Gold Deposit, Tajikistan) to detect gold
      concentration from ores to find potential application in mining technology.

PMID- 29343697
TI  - Effluent and serum protein N-glycosylation is associated with inflammation and
      peritoneal membrane transport characteristics in peritoneal dialysis patients.
AB  - Mass spectrometric glycomics was used as an innovative approach to identify
      biomarkers in serum and dialysate samples from peritoneal dialysis (PD) patients.
      PD is a life-saving treatment worldwide applied in more than 100,000 patients
      suffering from chronic kidney disease. PD treatment uses the peritoneum as a
      natural membrane to exchange waste products from blood to a glucose-based
      solution. Daily exposure of the peritoneal membrane to these solutions may cause
      complications such as peritonitis, fibrosis and inflammation which, in the long
      term, lead to the failure of the treatment. It has been shown in the last years
      that protein N-glycosylation is related to inflammatory and fibrotic processes.
      Here, by using a recently developed MALDI-TOF-MS method with linkage-specific
      sialic acid derivatisation, we showed that alpha2,6-sialylation, especially in
      triantennary N-glycans from peritoneal effluents, is associated with critical
      clinical outcomes in a prospective cohort of 94 PD patients. Moreover, we found
      an association between the levels of presumably immunoglobulin-G-related glycans
      as well as galactosylation of diantennary glycans with PD-related complications
      such as peritonitis and loss of peritoneal mesothelial cell mass. The observed
      glycomic changes point to changes in protein abundance and protein-specific
      glycosylation, representing candidate functional biomarkers of PD and associated
      complications.

PMID- 29343698
TI  - Correlations between mitochondrial DNA haplogroup D5 and chronic hepatitis B
      virus infection in Yunnan, China.
AB  - Mitochondrial abnormality is frequently reported in individuals with hepatitis B
      virus (HBV) infection, but the associated hosts' mitochondrial genetic factors
      remain obscure. We hypothesized that mitochondria may affect host susceptibility
      to HBV infection. In this study, we aimed to detect the association between
      chronic HBV infection and mitochondrial DNA in Chinese from Yunnan, Southwest
      China. A total of 272 individuals with chronic HBV infection (CHB), 310 who had
      never been infected by HBV (healthy controls, HC) and 278 with a trace of HBV
      infection (spontaneously recovered, SR) were analysed for mtDNA sequence
      variations and classified into respective haplogroups. Haplogroup frequencies
      were compared between HBV infected patients, HCs and SRs. Haplogroup D5 presented
      a higher frequency in CHBs than in HCs (P = 0.017, OR = 2.87, 95% confidence
      interval [CI] = (1.21-6.81)) and SRs (P = 0.049, OR = 2.90, 95% CI = 1.01-8.35).
      The network of haplogroup D5 revealed a distinct distribution pattern between
      CHBs and non-CHBs. A trend of higher viral load among CHBs with haplogroup D5 was
      observed. Our results indicate the risk potential of mtDNA haplogroup D5 in
      chronic HBV infection in Yunnan, China.

PMID- 29343699
TI  - Collagen-Binding Hepatocyte Growth Factor (HGF) alone or with a Gelatin-
      furfurylamine Hydrogel Enhances Functional Recovery in Mice after Spinal Cord
      Injury.
AB  - The treatment of spinal cord injury (SCI) is currently a significant challenge.
      Hepatocyte growth factor (HGF) is a multipotent neurotrophic and
      neuroregenerative factor that can be beneficial for the treatment of SCI.
      However, immobilized HGF targeted to extracellular matrix may be more effective
      than diffusible, unmodified HGF. In this study, we evaluated the neurorestorative
      effects of an engineered HGF with a collagen biding domain (CBD-HGF). CBD-HGF
      remained in the spinal cord for 7 days after a single administration, while
      unmodified HGF was barely seen at 1 day. When a gelatin-furfurylamine (FA)
      hydrogel was applied on damaged spinal cord as a scaffold, CBD-HGF was retained
      in gelatin-FA hydrogel for 7 days, whereas HGF had faded by 1 day. A single
      administration of CBD-HGF enhanced recovery from spinal cord compression injury
      compared with HGF, as determined by motor recovery, and electrophysiological and
      immunohistochemical analyses. CBD-HGF alone failed to improve recovery from a
      complete transection injury, however CBD-HGF combined with gelatin-FA hydrogel
      promoted endogenous repair and recovery more effectively than HGF with hydrogel.
      These results suggest that engineered CBD-HGF has superior therapeutic effects
      than naive HGF. CBD-HGF combined with hydrogel scaffold may be promising for the
      treatment of serious SCI.

PMID- 29343700
TI  - Full-field thermal imaging of quasiballistic crosstalk reduction in nanoscale
      devices.
AB  - Understanding nanoscale thermal transport is of substantial importance for
      designing contemporary semiconductor technologies. Heat removal from small
      sources is well established to be severely impeded compared to diffusive
      predictions due to the ballistic nature of the dominant heat carriers.
      Experimental observations are commonly interpreted through a reduction of
      effective thermal conductivity, even though most measurements only probe a single
      aggregate thermal metric. Here, we employ thermoreflectance thermal imaging to
      directly visualise the 2D temperature field produced by localised heat sources on
      InGaAs with characteristic widths down to 100 nm. Besides displaying effective
      thermal performance reductions up to 50% at the active junctions in agreement
      with prior studies, our steady-state thermal images reveal that, remarkably, 1-3
      MUm adjacent to submicron devices the crosstalk is actually reduced by up to
      fourfold. Submicrosecond transient imaging additionally shows responses to be
      faster than conventionally predicted. A possible explanation based on
      hydrodynamic heat transport, and some open questions, are discussed.

PMID- 29343701
TI  - Alanine mutation of the catalytic sites of Pantothenate Synthetase causes
      distinct conformational changes in the ATP binding region.
AB  - The enzyme Pantothenate synthetase (PS) represents a potential drug target in
      Mycobacterium tuberculosis. Its X-ray crystallographic structure has demonstrated
      the significance and importance of conserved active site residues including
      His44, His47, Asn69, Gln72, Lys160 and Gln164 in substrate binding and formation
      of pantoyl adenylate intermediate. In the current study, molecular mechanism of
      decreased affinity of the enzyme for ATP caused by alanine mutations was
      investigated using molecular dynamics (MD) simulations and free energy
      calculations. A total of seven systems including wild-type + ATP, H44A + ATP,
      H47A + ATP, N69A + ATP, Q72A + ATP, K160A + ATP and Q164A + ATP were subjected to
      50 ns MD simulations. Docking score, MM-GBSA and interaction profile analysis
      showed weak interactions between ATP (substrate) and PS (enzyme) in H47A and
      H160A mutants as compared to wild-type, leading to reduced protein catalytic
      activity. However, principal component analysis (PCA) and free energy landscape
      (FEL) analysis revealed that ATP was strongly bound to the catalytic core of the
      wild-type, limiting its movement to form a stable complex as compared to mutants.
      The study will give insight about ATP binding to the PS at the atomic level and
      will facilitate in designing of non-reactive analogue of pantoyl adenylate which
      will act as a specific inhibitor for PS.

PMID- 29343702
TI  - Analysis of mitochondrial function in human induced pluripotent stem cells from
      patients with mitochondrial diabetes due to the A3243G mutation.
AB  - We previously established human induced pluripotent stem (iPS) cells in two
      diabetic patients from different families with the mitochondrial A3243G mutation
      and isolated isogenic iPS cell clones with either undetectable or high levels of
      the mutation in both patients. In the present study, we analyzed the
      mitochondrial functions of two mutation-undetectable and two mutation-high clones
      in each patient through four methods to assess complex I activity, mitochondrial
      membrane potential, mitochondrial respiration, and mitochondrial ATP production.
      In the first patient, complex I activity, mitochondrial respiration, and
      mitochondrial ATP production were decreased in the mutation-high clones compared
      with the mutation-undetectable clones, and mitochondrial membrane potential was
      decreased in a mutation-high clone compared with a mutation-undetectable clone.
      In the second patient, complex I activity was decreased in one mutation-high
      clone compared with the other clones. The other parameters showed no differences
      in any clones. In addition, the complex I activity and mitochondrial respiration
      of the mutation-undetectable clones from both patients were located in the range
      of those of iPS cells from healthy subjects. The present study suggests that the
      mitochondrial function of the mutation-undetectable iPS cell clones obtained from
      two patients with the A3243G mutation is comparable to the control iPS cells.

PMID- 29343703
TI  - A novel microRNA, hsa-miR-6852 differentially regulated by Interleukin-27 induces
      necrosis in cervical cancer cells by downregulating the FoxM1 expression.
AB  - We have previously demonstrated that Interleukin-27 differentially regulates the
      expression of seven novel microRNAs. Here we elucidate the functional
      significance of these novel microRNAs. Of the seven microRNAs, over expression of
      miRNA-6852 (miR-SX4) mimic induces cell cycle arrest at G2/M phase and induces
      necrosis in HEK293 and panel of cervical cancer cells (Human Papilloma Virus
      (HPV) infected cell lines; HeLa, CaSki and SiHa cells). To define the mechanism
      of the miR-SX4-mediated G2/M arrest, a microarray gene chip array and western
      blot analysis were performed. FoxM1, a transcription factor is identified as a
      key protein down-regulated by miR-SX4, even though the miR-SX4 does not target
      3'UTR of FoxM1. Knock down of FoxM1 using si-RNA demonstrate that FoxM1 silenced
      cell induces G2/M cell cycle arrest and necrosis. Our data demonstrated for the
      first time that miR-SX4 could be a potent anti-cancer microRNA.

PMID- 29343704
TI  - Phosphorylation induced cochaperone unfolding promotes kinase recruitment and
      client class-specific Hsp90 phosphorylation.
AB  - During the Hsp90-mediated chaperoning of protein kinases, the core components of
      the machinery, Hsp90 and the cochaperone Cdc37, recycle between different
      phosphorylation states that regulate progression of the chaperone cycle. We show
      that Cdc37 phosphorylation at Y298 results in partial unfolding of the C-terminal
      domain and the population of folding intermediates. Unfolding facilitates Hsp90
      phosphorylation at Y197 by unmasking a phosphopeptide sequence, which serves as a
      docking site to recruit non-receptor tyrosine kinases to the chaperone complex
      via their SH2 domains. In turn, Hsp90 phosphorylation at Y197 specifically
      regulates its interaction with Cdc37 and thus affects the chaperoning of only
      protein kinase clients. In summary, we find that by providing client class
      specificity, Hsp90 cochaperones such as Cdc37 do not merely assist in client
      recruitment but also shape the post-translational modification landscape of Hsp90
      in a client class-specific manner.

PMID- 29343705
TI  - Nanoscale Structural Modulation and Low-temperature Magnetic Response in Mixed
      layer Aurivillius-type Oxides.
AB  - Nanoscale structural modulation with different layer numbers in layer-structured
      complex oxides of the binary Bi4Ti3O12-BiFeO3 system can give rise to intriguing
      phenomena and extraordinary properties, originating from the correlated
      interfaces of two different phases with different strain states. In this work, we
      studied the nanoscale structural modulation induced by Co-substitution in the
      Aurivillius-type oxide of Bi11Fe3Ti6O33 with a unique and naturally occurred
      mixed-layer structure. Nanoscale structural evolution via doping occurred from
      the phase-modulated structure composed of 4- and 5-layer phases to a homogeneous
      4-layer structure was clearly observed utilizing x-ray diffraction and electron
      micro-techniques. Significantly, magnetic response for the samples under various
      temperatures was recorded and larger magnetic coercive fields (e.g. H c  ~ 10 kOe
      at 50 K) were found in the phase-modulated samples. Analyses of the x-ray
      absorption spectra and magnetic response confirmed that the low-temperature
      magnetic behaviour should be intrinsic to the phase-modulated structure inside
      the structural transformation region, mainly arising from structural distortions
      at the correlated interfaces.

PMID- 29343706
TI  - Caloric restriction lowers endocannabinoid tonus and improves cardiac function in
      type 2 diabetes.
AB  - BACKGROUND/OBJECTIVES: Endocannabinoids (ECs) are associated with obesity and
      ectopic fat accumulation, both of which play a role in the development of
      cardiovascular disease (CVD) in type 2 diabetes (T2D). The effect of prolonged
      caloric restriction on ECs in relation to fat distribution and cardiac function
      is still unknown. Therefore, our aim was to investigate this relationship in
      obese T2D patients with coronary artery disease (CAD). SUBJECTS/METHODS: In a
      prospective intervention study, obese T2D patients with CAD (n = 27) followed a
      16 week very low calorie diet (VLCD; 450-1000 kcal/day). Cardiac function and fat
      accumulation were assessed with MRI and spectroscopy. Plasma levels of lipid
      species, including ECs, were measured using liquid chromatography-mass
      spectrometry. RESULTS: VLCD decreased plasma levels of virtually all measured
      lipid species of the class of N-acylethanolamines including the EC anandamide
      (AEA; -15%, p = 0.016), without decreasing monoacylglycerols including the EC 2
      arachidonoylglycerol (2-AG). Baseline plasma AEA levels strongly correlated with
      the volume of subcutaneous white adipose tissue (SAT; R2 = 0.44, p < 0.001). VLCD
      decreased the volume of SAT (-53%, p < 0.001), visceral white adipose tissue
      (VAT) (-52%, p < 0.001), epicardial white adipose tissue (-15%, p < 0.001) and
      paracardial white adipose tissue (-28%, p < 0.001). VLCD also decreased hepatic (
      86%, p < 0.001) and myocardial (-33%, p < 0.001) fat content. These effects were
      accompanied by an increased left ventricular ejection fraction (54.8 +/- 8.7-56.2
      +/- 7.9%, p = 0.016). CONCLUSIONS: Caloric restriction in T2D patients with CAD
      decreases AEA levels, but not 2-AG levels, which is paralleled by decreased lipid
      accumulation in adipose tissue, liver and heart, and improved cardiovascular
      function. Interestingly, baseline AEA levels strongly correlated with SAT volume.
      We anticipate that dietary interventions are worthwhile strategies in advanced
      T2D, and that reduction in AEA may contribute to the improved cardiometabolic
      phenotype induced by weight loss.

PMID- 29343707
TI  - Sensory neuronal P2RX4 receptors controls BDNF signaling in inflammatory pain.
AB  - Chronic inflammatory and neuropathic pains are major public health concerns.
      Potential therapeutic targets include the ATP-gated purinergic receptors (P2RX)
      that contribute to these pathological types of pain in several different cell
      types. The purinergic receptors P2RX2 and P2RX3 are expressed by a specific
      subset of dorsal root ganglion neurons and directly shape pain processing by
      primary afferents. In contrast the P2RX4 and P2RX7 are mostly expressed in
      myeloid cells, where activation of these receptors triggers the release of
      various pro-inflammatory molecules. Here, we demonstrate that P2RX4 also controls
      calcium influx in mouse dorsal root ganglion neurons. P2RX4 is up-regulated in
      pain-processing neurons during long lasting peripheral inflammation and it co
      localizes with Brain-Derived Neurotrophic Factor (BDNF). In the dorsal horn of
      the spinal cord, BDNF-dependent signaling pathways, phosphorylation of Erk1/2 and
      of the GluN1 subunit as well as the down regulation of the co-transporter KCC2,
      which are triggered by peripheral inflammation are impaired in P2RX4-deficient
      mice. Our results suggest that P2RX4, expressed by sensory neurons, controls
      neuronal BDNF release that contributes to hyper-excitability during chronic
      inflammatory pain and establish P2RX4 in sensory neurons as a new potential
      therapeutic target to treat hyperexcitability during chronic inflammatory pain.

PMID- 29343708
TI  - Pteropods counter mechanical damage and dissolution through extensive shell
      repair.
AB  - The dissolution of the delicate shells of sea butterflies, or pteropods, has
      epitomised discussions regarding ecosystem vulnerability to ocean acidification
      over the last decade. However, a recent demonstration that the organic coating of
      the shell, the periostracum, is effective in inhibiting dissolution suggests that
      pteropod shells may not be as susceptible to ocean acidification as previously
      thought. Here we use micro-CT technology to show how, despite losing the entire
      thickness of the original shell in localised areas, specimens of polar species
      Limacina helicina maintain shell integrity by thickening the inner shell wall.
      One specimen collected within Fram Strait with a history of mechanical and
      dissolution damage generated four times the thickness of the original shell in
      repair material. The ability of pteropods to repair and maintain their shells,
      despite progressive loss, demonstrates a further resilience of these organisms to
      ocean acidification but at a likely metabolic cost.

PMID- 29343709
TI  - Experimental and Numerical Investigation on Dragonfly Wing and Body Motion during
      Voluntary Take-off.
AB  - We present a detailed analysis of the voluntary take-off procedure of a
      dragonfly. The motions of the body and wings are recorded using two high-speed
      cameras at Beihang University. The experimental results show that the dragonfly
      becomes airborne after approximately one wingbeat and then leaves the ground.
      During this process, the maximum vertical acceleration could reach 20 m/s2.
      Evidence also shows that acceleration is generated only by the aerodynamic force
      induced by the flapping of wings. The dragonfly voluntary take-off procedure is
      divided into four phases with distinctive features. The variation in phase
      difference between the forewing and hindwing and angle of attack in the down
      stroke are calculated to explain the different features of the four phases. In
      terms of the key parameters of flapping, the phase difference increases from
      approximately 0 to 110 degrees; the angle of attack in down-stroke reaches the
      maximum at first and then decreases in the following take-off procedure. Due to
      experimental limitations, 2-D simulations are conducted using the immersed
      boundary method. The results indicate that the phase difference and the angle of
      attack are highly correlated with the unsteady fluid field around the dragonfly's
      wings and body, which determines the generation of aerodynamic forces.

PMID- 29343711
TI  - Silver Nanoparticles in the Water Environment in Malaysia: Inspection,
      characterization, removal, modeling, and future perspective.
AB  - The current status of silver nanoparticles (AgNPs) in the water environment in
      Malaysia was examined and reported. For inspection, two rivers and two sewage
      treatment plants (STPs) were selected. Two activated carbons derived from oil
      palm (ACfOPS) and coconut (ACfCS) shells were proposed as the adsorbent to remove
      AgNPs. It was found that the concentrations of AgNPs in the rivers and STPs are
      in the ranges of 0.13 to 10.16 mg L-1 and 0.13 to 20.02 mg L-1, respectively,
      with the highest concentration measured in July. ACfOPS and ACfCS removed up to
      99.6 and 99.9% of AgNPs, respectively, from the water. The interaction mechanism
      between AgNPs and the activated carbon surface employed in this work was mainly
      the electrostatic force interaction via binding Ag+ with O- presented in the
      activated carbon to form AgO. Fifteen kinetic models were compared statistically
      to describe the removal of AgNPs. It was found that the experimental adsorption
      data can be best described using the mixed 1,2-order model. Therefore, this model
      has the potential to be a candidate for a general model to describe AgNPs
      adsorption using numerous materials, its validation of which has been confirmed
      with other material data from previous works.

PMID- 29343710
TI  - Phenotypic diversity identified by cardiac magnetic resonance in a large
      hypertrophic cardiomyopathy family with a single MYH7 mutation.
AB  - Limited data is available on phenotypic variations with the same genotype in
      hypertrophic cardiomyopathy (HCM). The present study aims to explore the
      relationship between genotype and phenotype characterized by cardiovascular
      magnetic resonance (CMR) in a large Chinese family. A proband diagnosed with HCM
      from a multigenerational family underwent next-generation sequencing based on a
      custom sureSelect panel, including 117 candidate pathogenic genes associated with
      cardiomyopathies. All genetic results were confirmed by the Sanger sequencing
      method. All confirmed mutation carriers underwent CMR exam and myocardial tissue
      characterization using T1 mapping and late gadolinium enhancement (LGE) on a 3T
      scanner (Siemens Trio, Gemany). After clinical and genetic screening of 36
      (including the proband) members of a large Chinese family, nineteen family
      members are determined to carry the single p.T1377M (c.4130C>T) mutation in the
      MYH7 gene. Of these 19 mutation carriers, eight are diagnosed with HCM, one was
      considered as borderline affected and ten are not clinically or phenotypically
      affected. Different HCM phenotypes are present in the nine affected individuals
      in this family. In addition, we have found different tissue characteristics
      assessed by T1 mapping and LGE in these individuals. We describe a family that
      demonstrates the diverse HCM phenotypes associated with a single MYH7 mutation.

PMID- 29343713
TI  - Atmospheric CO2 effect on stable carbon isotope composition of terrestrial fossil
      archives.
AB  - The 13C/12C ratio of C3 plant matter is thought to be controlled by the isotopic
      composition of atmospheric CO2 and stomatal response to environmental conditions,
      particularly mean annual precipitation (MAP). The effect of CO2 concentration on
      13C/12C ratios is currently debated, yet crucial to reconstructing ancient
      environments and quantifying the carbon cycle. Here we compare high-resolution
      ice core measurements of atmospheric CO2 with fossil plant and faunal isotope
      records. We show the effect of pCO2 during the last deglaciation is stronger for
      gymnosperms (-1.4 +/- 1.20/00) than angiosperms/fauna (-0.5 +/- 1.50/00), while
      the contributions from changing MAP are -0.3 +/- 0.60/00 and -0.4 +/- 0.40/00,
      respectively. Previous studies have assumed that plant 13C/12C ratios are mostly
      determined by MAP, an assumption which is sometimes incorrect in geological time.
      Atmospheric effects must be taken into account when interpreting terrestrial
      stable carbon isotopes, with important implications for past environments and
      climates, and understanding plant responses to climate change.

PMID- 29343712
TI  - Zika virus infection in pregnant rhesus macaques causes placental dysfunction and
      immunopathology.
AB  - Zika virus (ZIKV) infection during pregnancy leads to an increased risk of fetal
      growth restriction and fetal central nervous system malformations, which are
      outcomes broadly referred to as the Congenital Zika Syndrome (CZS). Here we
      infect pregnant rhesus macaques and investigate the impact of persistent ZIKV
      infection on uteroplacental pathology, blood flow, and fetal growth and
      development. Despite seemingly normal fetal growth and persistent fetal-placenta
      maternal infection, advanced non-invasive in vivo imaging studies reveal dramatic
      effects on placental oxygen reserve accompanied by significantly decreased oxygen
      permeability of the placental villi. The observation of abnormal oxygen transport
      within the placenta appears to be a consequence of uterine vasculitis and
      placental villous damage in ZIKV cases. In addition, we demonstrate a robust
      maternal-placental-fetal inflammatory response following ZIKV infection. This
      animal model reveals a potential relationship between ZIKV infection and
      uteroplacental pathology that appears to affect oxygen delivery to the fetus
      during development.

PMID- 29343714
TI  - Endothelial nitric oxide synthase overexpressing human early outgrowth cells
      inhibit coronary artery smooth muscle cell migration through paracrine functions.
AB  - Cells mobilized from the bone marrow can contribute to endothelial regeneration
      and repair. Nevertheless, cardiovascular diseases are associated with diminished
      numbers and function of these cells, attenuating their healing potential. Gene
      transfer of endothelial nitric oxide synthase (eNOS) can restore the activity of
      circulating cells. Furthermore, estrogen accelerates the reendothelialization
      capacity of early outgrowth cells (EOCs). We hypothesized that overexpressing
      eNOS alone or in combination with estrogen stimulation in EOCs would potentiate
      the beneficial effects of these cells in regulating smooth muscle cell (SMC)
      function. Native human EOCs did not have any effect on human coronary artery SMC
      (hCASMC) proliferation or migration. Transfecting EOCs with a human eNOS plasmid
      and/or stimulating with 17beta-estradiol (E2) increased NO production 3-fold and
      enhanced EOC survival. Moreover, in co-culture studies, eNOS overexpressing or E2
      stimulated EOCs reduced hCASMC migration (by 23% and 56% respectively), vs.
      control EOCs. These effects do not implicate ERK1/2 or focal adhesion kinases.
      Nevertheless, NOS-EOCs had no effect on hCASMC proliferation. These results
      suggest that overexpressing or activating eNOS in EOCs increases their survival
      and enhances their capacity to regulate SMC migration through paracrine effects.
      These data elucidate how eNOS overexpression or activation in EOCs can prevent
      vascular remodeling.

PMID- 29343715
TI  - Effects of straw application on nitrate leaching in fields in the Yellow River
      irrigation zone of Ningxia, China.
AB  - A five-year field experiment was conducted to investigate the effects of straw
      application on nitrate leaching loss. Treatments included soil that was not
      treated (control), soil treated with straw at a low rate (4,500 kg ha-2, T1) and
      soil treated with straw at a high rate (9,000 kg ha-2, T2). Nitrate-nitrogen
      leaching in the 10, 20, 30, 60, and 90 cm soil layers was measured using the
      resin-core method. The results indicated that straw application could reduce soil
      nitrate leaching losses in the 0-30 cm layer. In this layer, the nitrate leaching
      values for T1 (13.76 kg ha-2) and T2 (13.74 kg ha-2) were both significantly
      lower than those of the control (15.76 kg ha-2) (P < 0.05); the soil nitrate
      leaching losses decreased by 12.71% and 12.84% for those two treatments,
      respectively. However, no significant differences in losses were observed (P >
      0.05) between T1 and T2. The effects of straw application were apparent only in
      the ploughing layer (30 cm-depth soil layer). In the deeper layers (60 and 90
      cm), no significant differences were observed between the treatments and the
      control, and the same results were observed in the topsoil layers (10 and 20 cm).

PMID- 29343716
TI  - Expression of the methionine sulfoxide reductase lost during evolution extends
      Drosophila lifespan in a methionine-dependent manner.
AB  - Accumulation of oxidized amino acids, including methionine, has been implicated
      in aging. The ability to reduce one of the products of methionine oxidation, free
      methionine-R-sulfoxide (Met-R-SO), is widespread in microorganisms, but during
      evolution this function, conferred by the enzyme fRMsr, was lost in metazoa. We
      examined whether restoration of the fRMsr function in an animal can alleviate the
      consequences of methionine oxidation. Ectopic expression of yeast fRMsr supported
      the ability of Drosophila to catalyze free Met-R-SO reduction without affecting
      fecundity, food consumption, and response to starvation. fRMsr expression also
      increased resistance to oxidative stress. Moreover, it extended lifespan of flies
      in a methionine-dependent manner. Thus, expression of an oxidoreductase lost
      during evolution can enhance metabolic and redox functions and lead to an
      increase in lifespan in an animal model. More broadly, our study exposes the
      potential of a combination of genetic and nutritional strategies in lifespan
      control.

PMID- 29343717
TI  - The role of NFkappaB in spheroid formation of human breast cancer cells cultured
      on the Random Positioning Machine.
AB  - Human MCF-7 breast cancer cells were exposed to a Random Positioning Machine
      (RPM). After 24 hours (h) the cells grew either adherently within a monolayer
      (AD) or within multicellular spheroids (MCS). AD and MCS populations were
      separately harvested, their cellular differences were determined performing qPCR
      on genes, which were differently expressed in AD and MCS cells. Gene array
      technology was applied to detect RPM-sensitive genes in MCF-7 cells after 24 h.
      Furthermore, the capability to form multicellular spheroids in vitro was compared
      with the intracellular distribution of NF-kappaB (NFkappaB) p65. NFkappaB was
      equally distributed in static control cells, but predominantly localized in the
      cytoplasm in AD cells and nucleus in MCS cells exposed to the RPM. Gene array
      analyses revealed a more than 2-fold change of only 23 genes including some whose
      products are affected by oxygen levels or regulate glycolysis. Significant
      upregulations of the mRNAs of enzymes degrading heme, of ANXA1, ANXA2, CTGF, CAV2
      and ICAM1, as well as of FAS, Casp8, BAX, p53, CYC1 and PARP1 were observed in
      MCS cells as compared with 1g-control and AD cells. An interaction analysis of 47
      investigated genes suggested that HMOX-1 and NFkappaB variants are activated,
      when multicellular spheroids are formed.

PMID- 29343718
TI  - The bacterial Type III toxin-antitoxin system, ToxIN, is a dynamic protein-RNA
      complex with stability-dependent antiviral abortive infection activity.
AB  - Bacteria have evolved numerous defense systems to protect themselves from viral
      (bacteriophage) infection. The ToxIN system of Pectobacterium atrosepticum is a
      Type III toxin-antitoxin complex and "altruistic suicide" anti-phage system,
      which kills phage-infected cells through the release of a ribonuclease toxin,
      ToxN. ToxN is counteracted by a co-transcribed antitoxic RNA pseudoknot, ToxI,
      which self-assembles with ToxN into an inactive 3 ToxI:3 ToxN complex in vitro.
      However it is not known whether this complex is predominant in vivo, or how the
      complex is disassembled following infection to trigger a lethal, "altruistic"
      response. In this study, we characterise ToxI turnover and folding, and explore
      the link between complex stability and anti-phage activity, with a view to
      understanding events that lead to ToxN-mediated suicide following phage
      infection. We present evidence that ToxN constantly cleaves fresh ToxI in vivo
      rather than staying associated with pre-processed antitoxin, and that the ToxI
      antitoxin can partially fold spontaneously using conserved nucleotides. We also
      show that reducing the stability of the ToxIN complex can increase the strength
      of the antiviral response in a phage-dependent manner. Based on this information,
      we propose a revised model for ToxN inhibition, complex assembly and activation
      by infecting bacteriophage.

PMID- 29343719
TI  - The Significant Role of c-Abl Kinase in Barrier Altering Agonists-mediated
      Cytoskeletal Biomechanics.
AB  - Exploration of human pulmonary artery endothelial cell (EC) as a prototypical
      biomechanical system has important pathophysiologic relevance because this cell
      type plays a key role in the development of a wide variety of clinical
      conditions. The complex hierarchical organization ranging from the molecular
      scale up to the cellular level has an intimate and intricate relationship to the
      barrier function between lung tissue and blood. To understand the innate molecule
      cell-tissue relationship across varied length-scales, the functional role of c
      Abl kinase in the cytoskeletal nano-biomechanics of ECs in response to barrier
      altering agonists was investigated using atomic force microscopy. Concurrently,
      the spatially specific arrangement of cytoskeleton structure and dynamic
      distribution of critical proteins were examined using scanning electron
      microscopy and immunofluorescence. Reduction in c-Abl expression by siRNA
      attenuates both thrombin- and sphingosine 1-phosphate (S1P)-mediated structural
      changes in ECs, specifically spatially-defined changes in elastic modulus and
      distribution of critical proteins. These results indicate that c-Abl kinase is an
      important determinant of cortical actin-based cytoskeletal rearrangement. Our
      findings directly bridge the gap between kinase activity, structural complexity,
      and functional connectivity across varied length-scales, and suggest that
      manipulation of c-Abl kinase activity may be a potential target for the treatment
      of pulmonary barrier disorders.

PMID- 29343720
TI  - Associations between VDR Gene Polymorphisms and Osteoporosis Risk and Bone
      Mineral Density in Postmenopausal Women: A systematic review and Meta-Analysis.
AB  - Results on the relationships between vitamin D receptor (VDR) gene polymorphisms
      and postmenopausal osteoporosis (PMOP) susceptibility and bone mineral density
      (BMD) are conflicting. The aim of the study is to identify more eligible studies
      that calculated pooled OR and WMD with 95% CI to assess their associations.
      Overall, there were significant correlations between VDR ApaI, VDR FokI and PMOP
      susceptibility. Subgroup analysis showed that VDR ApaI polymorphism significantly
      decreased the osteoporosis risk in Caucasian postmenopausal women. In Asian
      populations, VDR BsmI and VDR FokI were associated with an increased risk of
      PMOP. As to the associations between VDR polymorphisms and BMD, Caucasian PMOP
      women carrying the ApaI aa genotype were at risk of high BMD in femoral neck, and
      low femoral neck BMD was observed in Caucasian PMOP women with FokI Ff genotype.
      PMOP women with the Cdx2 GA genotype had a lower lumbar spine BMD in overall and
      Caucasian populations compared with PMOP women with GG genotype. Different VDR
      gene polymorphisms have different impacts on PMOP risk and BMD.

PMID- 29343721
TI  - ?133p53 isoform promotes tumour invasion and metastasis via interleukin-6
      activation of JAK-STAT and RhoA-ROCK signalling.
AB  - ?122p53 mice (a model of ?133p53 isoform) are tumour-prone, have extensive
      inflammation and elevated serum IL-6. To investigate the role of IL-6 we crossed
      ?122p53 mice with IL-6 null mice. Here we show that loss of IL-6 reduced JAK-STAT
      signalling, tumour incidence and metastasis. We also show that ?122p53 activates
      RhoA-ROCK signalling leading to tumour cell invasion, which is IL-6-dependent and
      can be reduced by inhibition of JAK-STAT and RhoA-ROCK pathways. Similarly, we
      show that Delta133p53 activates these pathways, resulting in invasive and
      migratory phenotypes in colorectal cancer cells. Gene expression analysis of
      colorectal tumours showed enrichment of GPCR signalling associated with ?133TP53
      mRNA. Patients with elevated ?133TP53 mRNA levels had a shorter disease-free
      survival. Our results suggest that ?133p53 promotes tumour invasion by activation
      of the JAK-STAT and RhoA-ROCK pathways, and that patients whose tumours have high
      ?133TP53 may benefit from therapies targeting these pathways.

PMID- 29343722
TI  - Multiplex glycan bead array for high throughput and high content analyses of
      glycan binding proteins.
AB  - Glycan-binding proteins (GBPs) play critical roles in diverse cellular functions
      such as cell adhesion, signal transduction and immune response. Studies of the
      interaction between GBPs and glycans have been hampered by the availability of
      high throughput and high-content technologies. Here we report multiplex glycan
      bead array (MGBA) that allows simultaneous analyses of 384 samples and up to 500
      glycans in a single assay. The specificity, sensitivity and reproducibility of
      MGBA are evaluated using 39 plant lectins, 13 recombinant anti-glycan antibodies,
      and mammalian GBPs. We demonstrate the utility of this platform by the analyses
      of natural anti-glycan IgM and IgG antibodies in 961 human serum samples and the
      discovery of anti-glycan antibody biomarkers for ovarian cancer. Our data
      indicate that the MGBA platform is particularly suited for large population-based
      studies that require the analyses of large numbers of samples and glycans.

PMID- 29343723
TI  - Pharmacological targeting of BET proteins attenuates radiation-induced lung
      fibrosis.
AB  - Radiation-induced lung injury has restricted radiotherapy for thoracic cancer.
      The purpose of this study was to investigate the radioprotective effects of
      bromodomain and extra terminal (BET) inhibitor JQ1 in a murine model of pulmonary
      damage. Chest computed tomography (CT) was performed in a rat model after 20 Gy
      radiation of the right thorax. And histological evaluation and protein
      expressions of irradiated tissue were analyzed to confirm the potential anti
      fibrosis effect of JQ1 and its underlying mechanisms. Moreover, colony formation
      assays were used to explore the effects of JQ1 on esophageal cancer Eca109 and
      breast cancer MCF7. JQ1 attenuated radiologic and histologic presentations of
      radiation-induced fibrosis, inflammatory reaction and pulmonary structural
      changes and the increase of Hounsfield units (HU) density and hydroxyproline
      content after radiation. Additionally, JQ1 suppressed BRD4, c-MYC, Collagen I,
      TGF-beta, p-NF-kappaB p65, p-Smad2 and p-Smad3 expressions after irradiation,
      repressed proliferation and transdifferentiation of lung fibroblasts, and
      impaired clonogenic survival of thoracic cancer cells. Collectively, our study
      demonstrated for the first time that BET Bromodomain inhibitor JQ1 protected
      normal lung tissue after radiation, and exerted a radiosensitizing effect in
      thoracic cancer cells.

PMID- 29343724
TI  - The UV filtering potential of drop-casted layers of frustules of three diatom
      species.
AB  - Diatoms are in focus as biological materials for a range of photonic
      applications. Many of these applications would require embedding a multitude of
      diatoms in a matrix (e.g. paint, creme or lacquer); however, most studies on the
      photonic and spectral properties of diatoms frustules (silica walls) have been
      carried out on single cells. In this study, for the first time, we test the
      spectral properties of layers of frustules of three diatom species (Coscinodiscus
      granii, Thalassiosira punctifera and Thalassiosira pseudonana), with special
      focus on transmission and reflectance in the UV range. The transmittance
      efficiency in the UV A and B range was: T. pseudonana (56-59%) >C. granii (53
      54%) >T. punctifera (18-21%) for the rinsed frustules. To investigate the
      underlying cause of these differences, we performed X-ray scattering analysis,
      measurement of layer thickness and microscopic determination of frustule
      nanostructures. We further tested dried intact cells in the same experimental
      setup. Based on these data we discuss the relative importance of crystal
      structure properties, nanostructure and quantity of material on the spectral
      properties of diatom layers. Characterization of the UV protection performance of
      layers of diatom frustules is of central relevance for their potential use as
      innovative bio-based UV filters.

PMID- 29343726
TI  - Remarkably High Hole Mobility Metal-Oxide Thin-Film Transistors.
AB  - High performance p-type thin-film transistor (p-TFT) was realized by a simple
      process of reactive sputtering from a tin (Sn) target under oxygen ambient, where
      remarkably high field-effect mobility (MU FE ) of 7.6 cm2/Vs, 140 mV/dec
      subthreshold slope, and 3 * 104 on-current/off-current were measured. In sharp
      contrast, the SnO formed by direct sputtering from a SnO target showed much
      degraded MU FE , because of the limited low process temperature of SnO and
      sputtering damage. From the first principle quantum-mechanical calculation, the
      high hole MU FE of SnO p-TFT is due to its considerably unique merit of the small
      effective mass and single hole band without the heavy hole band. The high
      performance p-TFTs are the enabling technology for future ultra-low-power
      complementary-logic circuits on display and three-dimensional brain-mimicking
      integrated circuits.

PMID- 29343725
TI  - The phosphatase PPM1A controls monocyte-to-macrophage differentiation.
AB  - Differentiation of circulating monocytes into tissue-bound or tissue-resident
      macrophages is a critical regulatory process affecting host defense and
      inflammation. However, the regulatory signaling pathways that control the
      differentiation of monocytes into specific and distinct functional macrophage
      subsets are poorly understood. Herein, we demonstrate that monocyte-to-macrophage
      differentiation is controlled by the Protein Phosphatase, Mg2+/Mn2+-dependent 1A
      (PPM1A). Genetic manipulation experiments demonstrated that overexpression of
      PPM1A attenuated the macrophage differentiation program, while knockdown of PPM1A
      expression accelerated the ability of monocytes to differentiate into
      macrophages. We identify imiquimod and Pam3CSK4 as two Toll-like receptor
      agonists that induce PPM1A expression, and show that increased expression of
      PPM1A at the onset of differentiation impairs cellular adherence, reduces
      expression of inflammatory (M1) macrophage-specific markers, and inhibits the
      production of inflammatory cytokines. Our findings reveal PPM1A as a negative
      threshold regulator of M1-type monocyte-to-macrophage differentiation,
      establishing it as a key phosphatase that orchestrates this program.

PMID- 29343727
TI  - PredCRP: predicting and analysing the regulatory roles of CRP from its binding
      sites in Escherichia coli.
AB  - Cyclic AMP receptor protein (CRP), a global regulator in Escherichia coli,
      regulates more than 180 genes via two roles: activation and repression. Few
      methods are available for predicting the regulatory roles from the binding sites
      of transcription factors. This work proposes an accurate method PredCRP to derive
      an optimised model (named PredCRP-model) and a set of four interpretable rules
      (named PredCRP-ruleset) for predicting and analysing the regulatory roles of CRP
      from sequences of CRP-binding sites. A dataset consisting of 169 CRP-binding
      sites with regulatory roles strongly supported by evidence was compiled. The
      PredCRP-model, using 12 informative features of CRP-binding sites, and
      cooperating with a support vector machine achieved a training and test accuracy
      of 0.98 and 0.93, respectively. PredCRP-ruleset has two activation rules and two
      repression rules derived using the 12 features and the decision tree method C4.5.
      This work further screened and identified 23 previously unobserved regulatory
      interactions in Escherichia coli. Using quantitative PCR for validation, PredCRP
      model and PredCRP-ruleset achieved a test accuracy of 0.96 (=22/23) and 0.91
      (=21/23), respectively. The proposed method is suitable for designing predictors
      for regulatory roles of all global regulators in Escherichia coli. PredCRP can be
      accessed at https://github.com/NctuICLab/PredCRP .

PMID- 29343728
TI  - Oxidation of SQSTM1/p62 mediates the link between redox state and protein
      homeostasis.
AB  - Cellular homoeostatic pathways such as macroautophagy (hereinafter autophagy) are
      regulated by basic mechanisms that are conserved throughout the eukaryotic
      kingdom. However, it remains poorly understood how these mechanisms further
      evolved in higher organisms. Here we describe a modification in the autophagy
      pathway in vertebrates, which promotes its activity in response to oxidative
      stress. We have identified two oxidation-sensitive cysteine residues in a
      prototypic autophagy receptor SQSTM1/p62, which allow activation of pro-survival
      autophagy in stress conditions. The Drosophila p62 homologue, Ref(2)P, lacks
      these oxidation-sensitive cysteine residues and their introduction into the
      protein increases protein turnover and stress resistance of flies, whereas
      perturbation of p62 oxidation in humans may result in age-related pathology. We
      propose that the redox-sensitivity of p62 may have evolved in vertebrates as a
      mechanism that allows activation of autophagy in response to oxidative stress to
      maintain cellular homoeostasis and increase cell survival.

PMID- 29343730
TI  - First estimates of Greenland shark (Somniosus microcephalus) local abundances in
      Arctic waters.
AB  - Baited remote underwater video cameras were deployed in the Eastern Canadian
      Arctic, for the purpose of estimating local densities of the long-lived Greenland
      shark within five deep-water, data-poor regions of interest for fisheries
      development and marine conservation in Nunavut, Canada. A total of 31 camera
      deployments occurred between July-September in 2015 and 2016 during joint
      exploratory fishing and scientific cruises. Greenland sharks appeared at 80% of
      deployments. A total of 142 individuals were identified and no individuals were
      observed in more than one deployment. Estimates of Greenland shark abundance and
      biomass were calculated from averaged times of first arrival, video-derived
      swimming speed and length data, and local current speed estimates. Density
      estimates varied 1-15 fold among regions; being highest in warmer (>0  degrees
      C), deeper areas and lowest in shallow, sub-zero temperature regions. These
      baited camera results illustrate the ubiquity of this elusive species and suggest
      that Nunavut's Lancaster Sound eco-zone may be of particular importance for
      Greenland shark, a potentially vulnerable Arctic species.

PMID- 29343729
TI  - Drug self-assembly for synthesis of highly-loaded antimicrobial drug-silica
      particles.
AB  - Antimicrobial drug release from biomaterials for orthopedic repair and dental
      restorations can prevent biofilm growth and caries formation. Carriers for drug
      incorporation would benefit from long-term drug storage, controlled release, and
      structural stability. Mesoporous silica, synthesized through a co-assembly of
      silica and surfactant template, is an ideal drug encapsulation scaffold that
      maintains structural integrity upon release. However, conventional loading of
      drug within meso-silica pores via concentration-gradient diffusion limits the
      overall payload, concentration uniformity, and drug release control. Herein we
      demonstrate the co-assembly of an antimicrobial drug (octenidine dihydrochloride,
      OCT), and silica, to form highly-loaded (35% wt.) OCT-silica nanocomposite
      spheres of 500 nm diameter. Drug release significantly outlasted conventional OCT
      loaded mesoporous silica, closely fit Higuchi models of diffusive release, and
      was visualized via electron microscopy. Extension of this concept to the broad
      collection of self-assembling drugs grants biomedical community a powerful tool
      for synthesizing drug-loaded inorganic nanomaterials from the bottom-up.

PMID- 29343731
TI  - Impact of tissue kinetic heterogeneity on PET quantification: case study with the
      L-[1-11C]leucine PET method for cerebral protein synthesis rates.
AB  - Functional quantification with PET is generally based on modeling that assumes
      tissue regions are kinetically homogeneous. Even in regions sufficiently small to
      approach homogeneity, spillover due to resolution limitations of PET scanners may
      introduce heterogeneous kinetics into measured data. Herein we consider effects
      of kinetic heterogeneity at the smallest volume accessible, the single image
      voxel. We used L-[1-11C]leucine PET and compared rates of cerebral protein
      synthesis (rCPS) estimated voxelwise with methods that do (Spectral Analysis
      Iterative Filter, SAIF) and do not (Basis Function Method, BFM) allow for kinetic
      heterogeneity. In high resolution PET data with good counting statistics BFM
      produced estimates of rCPS comparable to SAIF, but at lower computational cost;
      thus the simpler, less costly method can be applied. With poorer counting
      statistics (lower injected radiotracer doses), BFM estimates were more biased. In
      data smoothed to simulate lower resolution PET, BFM produced estimates of rCPS 9
      14% higher than SAIF, overestimation consistent with applying a homogeneous
      tissue model to kinetically heterogeneous data. Hence with lower resolution data
      it is necessary to account for kinetic heterogeneity in the analysis. Kinetic
      heterogeneity may impact analyses of other tracers and scanning protocols
      differently; assessments should be made on a case by case basis.

PMID- 29343732
TI  - The neural correlates of the unified percept of alcohol-related craving: a fMRI
      and EEG study.
AB  - Alcohol addiction is accompanied by aberrant neural activity. Previously, task
      based fMRI and resting-state EEG studies have revealed that craving, a critical
      component of addiction, is linked to abnormal activity in cortical regions
      including the dorsal anterior cingulate cortex (dACC), nucleus accumbens (NAcc),
      posterior cingulate cortex (PCC) and pregenual anterior cingulate cortex (pgACC),
      etc. In this study, we combine these two imaging techniques to investigate a
      group of alcohol-addicted patients and provide convergent evidence for the neural
      correlates of craving not only in alcohol but substance abuse in general. We
      observe abnormal BOLD signal levels in the dACC, NAcc, pgACC, PCC, amygdala, and
      parahippocampus (PHC) in a cue-reactivity fMRI experiment. These findings are
      consistent with increased beta-band activity in the dACC and pgACC in resting
      state EEG. We further observe desynchronization characterized by decreased
      functional connectivity in cue-based fMRI and hypersynchronization characterized
      by increased functional connectivity between these regions in the theta frequency
      band. The results of our study show a consistent pattern of alcohol craving
      elicited by external cues and internal desires. Given the advantage of superior
      spatial and temporal resolution, we hypothesize a "central craving network" that
      integrates the different aspects of alcohol addiction into a unified percept.

PMID- 29343734
TI  - Cooper Pairing in A Doped 2D Antiferromagnet with Spin-Orbit Coupling.
AB  - We study the two-dimensional Hubbard model with the Rashba type spin-orbit
      coupling within and beyond the mean-field theory. The antiferromagnetic ground
      state for the model at half-filling and the Cooper pairing induced by
      antiferromagnetic spin fluctuations near half-filling are examined based on the
      random-phase approximation. We show that the antiferromagnetic order is
      suppressed and the magnetic susceptibility turns out to be anisotropic in the
      presence of the spin-orbit coupling. Energy spectrums of transverse spin
      fluctuations are obtained and the effective interactions between holes mediated
      by antiferromagnetic spin fluctuations are deduced in the case of low hole
      doping. It seems that the spin-orbit coupling tends to form s+p-wave Cooper
      pairs, while the s+d-wave pairing is dominant when the spin-orbit coupling is
      absent.

PMID- 29343733
TI  - Serum vitamin D levels and risk of prevalent tuberculosis, incident tuberculosis
      and tuberculin skin test conversion among prisoners.
AB  - Poor vitamin D status has been associated with tuberculosis (TB); whether poor
      status is cause or consequence of disease is uncertain. We conducted a case
      control study and two nested case-control studies to determine whether vitamin D
      levels were associated with active TB, tuberculin skin test (TST) conversion, and
      risk of progression to the active TB in prisoners in Brazil. In multivariable
      conditional logistic regression, subnormal vitamin D levels (OR, 3.77; 95% CI,
      1.04-13.64) were more likely in prisoners with active TB. In contrast, vitamin D
      was not found to be a risk factor for either TST conversion (OR, 2.49; 95% CI,
      0.64-9.66) or progression to active disease (OR, 0.59; 95% CI, 0.13-2.62). Black
      race (OR, 11.52; 95% CI, 2.01-63.36), less than 4 years of schooling (OR, 2.70;
      95% CI, 0.90-8.16), cigarette smoking (OR, 0.23; 95% CI, 0.06-0.79) were
      identified as risk factors for TST conversion. Risk of progression to active TB
      was found to be associated with cigarette smoking (OR, 7.42; 95% CI, 1.23-44.70).
      Our findings in the prison population show that poor vitamin D status is more
      common in individuals with active TB, but is not a risk factor for acquisition of
      latent TB or progression to active TB.

PMID- 29343735
TI  - Increasing conversion efficiency of two-step photon up-conversion solar cell with
      a voltage booster hetero-interface.
AB  - Development of high-efficiency solar cells is one of the attractive challenges in
      renewable energy technologies. Photon up-conversion can reduce the transmission
      loss and is one of the promising concepts which improve conversion efficiency.
      Here we present an analysis of the conversion efficiency, which can be increased
      by up-conversion in a single-junction solar cell with a hetero-interface that
      boosts the output voltage. We confirm that an increase in the quasi-Fermi gap and
      substantial photocurrent generation result in a high conversion efficiency.

PMID- 29343736
TI  - Establishing a mental lexicon with cochlear implants: an ERP study with young
      children.
AB  - In the present study we explore the implications of acquiring language when
      relying mainly or exclusively on input from a cochlear implant (CI), a device
      providing auditory input to otherwise deaf individuals. We focus on the time
      course of semantic learning in children within the second year of implant use; a
      period that equals the auditory age of normal hearing children during which
      vocabulary emerges and extends dramatically. 32 young bilaterally implanted
      children saw pictures paired with either matching or non-matching auditory words.
      Their electroencephalographic responses were recorded after 12, 18 and 24 months
      of implant use, revealing a large dichotomy: Some children failed to show
      semantic processing throughout their second year of CI use, which fell in line
      with their poor language outcomes. The majority of children, though, demonstrated
      semantic processing in form of the so-called N400 effect already after 12 months
      of implant use, even when their language experience relied exclusively on the
      implant. This is slightly earlier than observed for normal hearing children of
      the same auditory age, suggesting that more mature cognitive faculties at the
      beginning of language acquisition lead to faster semantic learning.

PMID- 29343737
TI  - Moderate decline in select synaptic markers in the prefrontal cortex (BA9) of
      patients with Alzheimer's disease at various cognitive stages.
AB  - Synaptic loss, plaques and neurofibrillary tangles are viewed as hallmarks of
      Alzheimer's disease (AD). This study investigated synaptic markers in neocortical
      Brodmann area 9 (BA9) samples from 171 subjects with and without AD at different
      levels of cognitive impairment. The expression levels of vesicular glutamate
      transporters (VGLUT1&2), glutamate uptake site (EAAT2), post-synaptic density
      protein of 95 kD (PSD95), vesicular GABA/glycine transporter (VIAAT),
      somatostatin (som), synaptophysin and choline acetyl transferase (ChAT) were
      evaluated. VGLUT2 and EAAT2 were unaffected by dementia. The VGLUT1, PSD95,
      VIAAT, som, ChAT and synaptophysin expression levels significantly decreased as
      dementia progressed. The maximal decrease varied between 12% (synaptophysin) and
      42% (som). VGLUT1 was more strongly correlated with dementia than all of the
      other markers (polyserial correlation = -0.41). Principal component analysis
      using these markers was unable to differentiate the CDR groups from one another.
      Therefore, the status of the major synaptic markers in BA9 does not seem to be
      linked to the cognitive status of AD patients. The findings of this study suggest
      that the loss of synaptic markers in BA9 is a late event that is only weakly
      related to AD dementia.

PMID- 29343738
TI  - Critical conditions for escape of a high-speed fullerene from a BNC nanobeam
      after collision.
AB  - For a resonator-based nano-balance, the capability of capturing a nanoparticle is
      essential for it to measure the mass of the particle. In the present study, a
      clamped-clamped nanobeam from a Boron-Nitride and Carbon (BNC) nanotube acts as
      the nano-balance, and a fullerene, e.g., C60, is chosen as the particle, and the
      capturing capability is quantitatively estimated by the minimal escape velocity
      (MEV) of the fullerene from the nanobeam after collision. When centrally
      colliding with the nanobeam, the escape of fullerene depends on both incidence of
      fullerene and temperature of the system. When the colliding in the Boron-Nitride
      (BN) area of the beam surface, the nanoball escapes easier than that at the
      carbon area. The MEV of the nanoball is lower at higher temperature. As the
      nanoball sometimes slides for a few pica-seconds on the beam surface before being
      bounced out, the nanoball can escape only when the beam surface can provide the
      nanoball enough kinetic energy to overcome the van der Waals interaction between
      them. The capturing capability of the nano-balance can, thus, be improved by
      reducing the initial kinetic energy of the system.

PMID- 29343739
TI  - Qualitative systematic review of barriers and facilitators to self-management of
      chronic obstructive pulmonary disease: views of patients and healthcare
      professionals.
AB  - Self-management interventions for chronic obstructive pulmonary disease (COPD)
      can improve quality of life, reduce hospital admissions, and improve symptoms.
      However, many factors impede engagement for patients and practitioners.
      Qualitative research, with its focus on subjective experience, can provide
      invaluable insights into such factors. Therefore, a systematic review and
      synthesis of qualitative evidence on COPD self-management from the perspective of
      patients, carers, and practitioners was conducted. Following a systematic search
      and screening, 31 studies were appraised and data extracted for analysis. This
      review found that patients can adapt to COPD; however, learning to self-manage is
      often a protracted process. Emotional needs are considerable; frustration,
      depression, and anxiety are common. In addition, patients can face an assortment
      of losses and limitations on their lifestyle and social interaction. Over time,
      COPD can consume their existence, reducing motivation. Support from family can
      prove vital, yet tinged with ambivalence and burden. Practitioners may not have
      sufficient time, resources, or appropriate skills or confidence to provide
      effective self-management support, particularly in regard to patients'
      psychosocial needs. This can compound patients' capability to engage in self
      management. For COPD self-management to be effective, patients' psychosocial
      needs must be prioritised alongside medication and exacerbation management. In
      addition, patients' personal beliefs regarding COPD and its management should be
      reviewed periodically to avoid problematic behaviours and enhance positive
      adaptions to the disease. Patients with COPD are not a homogenous group and no
      one intervention will prove effective for all. Finally, practitioners require
      greater education, training, and support to successfully assist patients.

PMID- 29343740
TI  - Modifiable lifestyle behaviors, but not a genetic risk score, associate with
      metabolic syndrome in evening chronotypes.
AB  - Evening chronotype associates with health complications possibly via lifestyle
      factors, while the contribution of genetics is unknown. The aim was to study the
      relative contributions of genetics, lifestyle, and circadian-related
      physiological characteristics in metabolic risk of evening chronotype. In order
      to capture a biological contribution to chronotype, a genetic-risk-score (GRS),
      comprised of 15 chronotype-related variants, was tested. Moreover, a wide range
      of behavioral and emotional eating factors was studied within the same
      population. Chronotype, lifestyle, and metabolic syndrome (MetS) outcomes were
      assessed (n = 2,126), in addition to genetics (n = 1,693) and rest-activity/wrist
      temperature rhythms (n = 100). Evening chronotype associated with MetS and
      insulin resistance (P < 0.05), and several lifestyle factors including poorer
      eating behaviors, lower physical activity and later sleep and wake times. We
      observed an association between higher evening GRS and evening chronotype (P <
      0.05), but not with MetS. We propose a GRS as a tool to capture the biological
      component of the inter-individual differences in chronotype. Our data show that
      several modifiable factors such as sedentary lifestyle, difficulties in
      controlling the amount of food eaten, alcohol intake and later wake and bed times
      that characterized evening-types, may underlie chronotype-MetS relationship. Our
      findings provide insights into the development of strategies, particularly for
      evening chronotype.

PMID- 29343742
TI  - Highly effective and chemically stable surface enhanced Raman scattering
      substrates with flower-like 3D Ag-Au hetero-nanostructures.
AB  - We demonstrated flower-like 3D Ag-Au hetero-nanostructures on an indium tin oxide
      glass (ITO glass) for surface enhanced Raman scattering (SERS) applications. The
      flower-like 3D Ag nanostructures were obtained through electrodeposition with
      liquid crystalline soft template which is simple, controllable and cost
      effective. The flower-like 3D Ag-Au hetero-nanostructures were further fabricated
      by galvanic replacement reaction of gold (III) chloride trihydrate (HAuCl4.3H2O)
      solution and flower-like Ag. The flower-like Ag-Au hetero-nanostructure exhibited
      stronger SERS effects and better chemical stability compared with flower-like Ag
      nanostructure. The localized surface plasmon resonance (LSPR) spectra, field
      emission scanning electron microscope (FESEM) photos and Ag-Au ratios were
      studied which show that the surface morphology and shape of the flower-like Ag-Au
      hetero-nanostructure play significant roles in enhancing SERS. The flower-like 3D
      Ag-Au hetero-nanostructures fabricated by electrodeposition in liquid crystalline
      template and galvanic replacement reaction are simple, cheap, controllable and
      chemical stable. It is a good candidate for applications in SERS detection and
      imaging.

PMID- 29343744
TI  - Improved Linearity with Polarization Coulomb Field Scattering in AlGaN/GaN
      Heterostructure Field-Effect Transistors.
AB  - The single-tone power of the AlGaN/GaN heterostructure field-effect transistors
      (HFETs) with different gate widths was measured. A distinct improvement in device
      linearity was observed in the sample with a larger gate width. The analysis of
      the variation of the parasitic source access resistance showed that, as the gate
      bias is increased, the polarization Coulomb field scattering can offset the
      increased polar optical phonon scattering and improve the device linearity. This
      approach is shown to be effective in improving the device linearity of AlGaN/GaN
      HFETs.

PMID- 29343743
TI  - Expression and subcellular localisation of AID and APOBEC3 in adenoid and
      palatine tonsils.
AB  - Activation-induced cytidine deaminase (AID) and apolipoprotein B mRNA-editing
      catalytic polypeptide 3 (A3) family are cytidine deaminases that play critical
      roles in B-cell maturation, antiviral immunity and carcinogenesis. Adenoids and
      palatine tonsils are secondary lymphoid immune organs, in which AID and A3s are
      thought to have several physiological or pathological roles. However, the
      expression of AID or A3s in these organs has not been investigated. Therefore, we
      investigated the expression profiles of AID and A3s, using 67 samples of adenoids
      and palatine tonsils from patients, with reverse transcription quantitative
      polymerase chain reaction (RT-qPCR) and immunohistochemical analyses. AID and A3s
      expression levels in the adenoids and the palatine tonsils of the same individual
      significantly correlated with each other. Of note, AID expression level in the
      adenoids negatively correlated with the age (r = -0.373, P = 0.003). The younger
      group with adenoid vegetation and tonsillar hypertrophy showed more abundant AID
      expression than the older group with recurrent tonsillitis and peritonsillar
      abscesses (P = 0.026). Moreover, immunohistochemical analysis revealed the
      distribution of AID and A3s in the epithelial cells as well as germinal centres.
      The localisation of AID expression and its relation to age may contribute to
      adenoid vegetation and inflammation.

PMID- 29343745
TI  - Malaria infected red blood cells release small regulatory RNAs through
      extracellular vesicles.
AB  - The parasite Plasmodium falciparum causes the most severe form of malaria. Cell
      communication between parasites is an important mechanism to control population
      density and differentiation. The infected red blood cells (iRBCs) release small
      extracellular vesicles (EVs) that transfer cargoes between cells. The EVs
      synchronize the differentiation of the asexual parasites into gametocytes to
      initiate the transmission to the mosquito. Beside their role in parasite
      communication, EVs regulate vascular function. So far, the exact cargoes
      responsible for cellular communication remain unknown. We isolated EVs from
      cultured iRBCs to determine their small RNA content. We identified several types
      of human and plasmodial regulatory RNAs. While the miRNAs and tRNA-derived
      fragments were the most abundant human RNAs, we also found Y-RNAs, vault RNAs,
      snoRNAs and piRNAs. Interestingly, we found about 120 plasmodial RNAs, including
      mRNAs coding for exported proteins and proteins involved in drug resistance, as
      well as non-coding RNAs, such as rRNAs, small nuclear (snRNAs) and tRNAs. These
      data show, that iRBC-EVs carry small regulatory RNAs. A role in cellular
      communication is possible since the RNAs were transferred to endothelial cells.
      Furthermore, the presence of Plasmodium RNAs, in EVs suggests that they may be
      used as biomarker to track and detect disease.

PMID- 29343747
TI  - Computational trans-omics approach characterised methylomic and transcriptomic
      involvements and identified novel therapeutic targets for chemoresistance in
      gastrointestinal cancer stem cells.
AB  - We investigated the relationship between methylomic [5-methylation on
      deoxycytosine to form 5-methylcytosine (5mC)] and transcriptomic information in
      response to chemotherapeutic 5-fluorouracil (5-FU) exposure and cisplatin (CDDP)
      administration using the ornithine decarboxylase (ODC) degron-positive cancer
      stem cell model of gastrointestinal tumour. The quantification of 5mC methylation
      revealed various alterations in the size distribution and intensity of genomic
      loci for each patient. To summarise these alterations, we transformed all large
      volume data into a smooth function and treated the area as a representative value
      of 5mC methylation. The present computational approach made the methylomic data
      more accessible to each transcriptional unit and allowed to identify candidate
      genes, including the tumour necrosis factor receptor-associated factor 4 (TRAF4),
      as novel therapeutic targets with a strong response to anti-tumour agents, such
      as 5-FU and CDDP, and whose significance has been confirmed in a mouse model in
      vivo. The present study showed that 5mC methylation levels are inversely
      correlated with gene expression in a chemotherapy-resistant stem cell model of
      gastrointestinal cancer. This mathematical method can be used to simultaneously
      quantify and identify chemoresistant potential targets in gastrointestinal cancer
      stem cells.

PMID- 29343746
TI  - The Static Magnetic Field Remotely Boosts the Efficiency of Doxorubicin through
      Modulating ROS Behaviors.
AB  - Exposure to magnetic field (MF) can affect cellular metabolism remotely. Cardio
      toxic effects of Doxorubicin (DOXO) have limited clinical uses at high dose. MF
      due to its effect on reactive oxygen species (ROS) lifetime, may provide a
      suitable choice to boost the efficacy of this drug at low dose. Here, we
      investigated the potential effects of homogenous static magnetic field (SMF) on
      DOXO-induced toxicity and proliferation rate of cancer cells. The results
      indicated that SMF similar to DOXO decreased the cell viability as well as the
      proliferation rate of MCF-7 and HFF cells. Moreover, combination of 10 mT SMF and
      0.1 uM DOXO decreased the viability and proliferation rate of cancer and normal
      cells in a synergetic manner. In spite of high a GSH level in cancer cell, SMF
      boosts the generation and lifetime of ROS at low dose of DOXO, and overcame to
      GSH mediated drug resistance. The results also confirmed that SMF exposure
      decreased 50% iron content of cells, which is attributed to iron homeostasis. In
      conclusion, these findings suggest that SMF can decrease required dose of
      chemotherapy drugs such as DOXO and thereby decrease their side effect.

PMID- 29343741
TI  - Species Distribution Modelling: Contrasting presence-only models with plot
      abundance data.
AB  - Species distribution models (SDMs) are widely used in ecology and conservation.
      Presence-only SDMs such as MaxEnt frequently use natural history collections
      (NHCs) as occurrence data, given their huge numbers and accessibility. NHCs are
      often spatially biased which may generate inaccuracies in SDMs. Here, we test how
      the distribution of NHCs and MaxEnt predictions relates to a spatial abundance
      model, based on a large plot dataset for Amazonian tree species, using inverse
      distance weighting (IDW). We also propose a new pipeline to deal with
      inconsistencies in NHCs and to limit the area of occupancy of the species. We
      found a significant but weak positive relationship between the distribution of
      NHCs and IDW for 66% of the species. The relationship between SDMs and IDW was
      also significant but weakly positive for 95% of the species, and sensitivity for
      both analyses was high. Furthermore, the pipeline removed half of the NHCs
      records. Presence-only SDM applications should consider this limitation,
      especially for large biodiversity assessments projects, when they are
      automatically generated without subsequent checking. Our pipeline provides a
      conservative estimate of a species' area of occupancy, within an area slightly
      larger than its extent of occurrence, compatible to e.g. IUCN red list
      assessments.

PMID- 29343748
TI  - Sac7 and Rho1 regulate the white-to-opaque switching in Candida albicans.
AB  - Candida albicans cells homozygous at the mating-type locus stochastically undergo
      the white-to-opaque switching to become mating-competent. This switching is
      regulated by a core circuit of transcription factors organized through
      interlocking feedback loops around the master regulator Wor1. Although a range of
      distinct environmental cues is known to induce the switching, the pathways
      linking the external stimuli to the central control mechanism remains largely
      unknown. By screening a C. albicans haploid gene-deletion library, we found that
      SAC7 encoding a GTPase-activating protein of Rho1 is required for the white-to
      opaque switching. We demonstrate that Sac7 physically associates with Rho1-GTP
      and the constitutively active Rho1G18V mutant impairs the white-to-opaque
      switching while the inactive Rho1D124A mutant promotes it. Overexpressing WOR1 in
      both sac7Delta/Delta and rho1 G18V cells suppresses the switching defect,
      indicating that the Sac7/Rho1 module acts upstream of Wor1. Furthermore, we
      provide evidence that Sac7/Rho1 functions in a pathway independent of the
      Ras/cAMP pathway which has previously been positioned upstream of Wor1. Taken
      together, we have discovered new regulators and a signaling pathway that regulate
      the white-to-opaque switching in the most prevalent human fungal pathogen C.
      albicans.

PMID- 29343750
TI  - Multi-wavelength growth of nanosecond laser-induced surface damage on fused
      silica gratings.
AB  - The nanosecond laser-induced damage growth phenomenon on the exit surface of
      fused silica grating is investigated at 1064 nm and 355 nm separately and also
      simultaneously. Experiments are first carried out on damage sites on a plane
      fused silica sample showing two different morphologies, and a damage type is
      selected for ensuring the repeatability of the subsequent tests. Comparing the
      mono-wavelength growth results on a grating and a plane fused silica sample, the
      periodic surface structure is found to be an aggravating factor for damage
      growth. This is highly supported by calculations of the enhancement of the
      optical electric field intensity thanks to Finite-Difference Time-Domain
      simulations. Finally, the mono-wavelength results enable us to quantify a
      coupling occurring in the multi-wavelength configuration, which could originate
      from the heating of the plasma (more likely produced in the ultraviolet)
      preferentially by the infrared pulse. This study provides interesting results
      about the involvement of the surface topography in damage growth, and paves the
      way towards the comprehension of this phenomenon at high-energy nanosecond laser
      facilities where fused silica gratings are simultaneously irradiated at several
      wavelengths.

PMID- 29343749
TI  - Testosterone boosts physical activity in male mice via dopaminergic pathways.
AB  - Low testosterone (T) in men, especially its free fraction, has been associated
      with loss of energy. In accordance, orchidectomy (ORX) in rodents results in
      decreased physical activity. Still, the mechanisms through which T stimulates
      activity remain mostly obscure. Here, we studied voluntary wheel running behavior
      in three different mouse models of androgen deficiency: ORX, androgen receptor
      (AR) knock-out (ARKO) and sex hormone binding globulin (SHBG)-transgenic mice, a
      novel mouse model of "low free T". Our results clearly show a fast and dramatic
      action of T stimulating wheel running, which is not explained by its action on
      muscle, as evidenced by neuromuscular studies and in a muscle-specific
      conditional ARKO mouse model. The action of T occurs via its free fraction, as
      shown by the results in SHBG-transgenic mice, and it implies both androgenic and
      estrogenic pathways. Both gene expression and functional studies indicate that T
      modulates the in vivo sensitivity to dopamine (DA) agonists. Furthermore, the
      restoration of wheel running by T is inhibited by treatment with DA antagonists.
      These findings reveal that the free fraction of T, both via AR and indirectly
      through aromatization into estrogens, stimulates physical activity behavior in
      male mice by acting on central DA pathways.

PMID- 29343751
TI  - Altered power spectral density in the resting-state sensorimotor network in
      patients with myotonic dystrophy type 1.
AB  - Myotonic dystrophy type 1 (DM1) is a multisystemic disease that involves the
      brain with several neurological symptoms. Although there were few imaging studies
      on DM1, no studies have investigated functional alterations in the sensorimotor
      network at rest in patients with DM1. In the current study, a power spectral
      density (PSD) analysis of resting-state fMRI data was performed to assess
      possible alteration in spontaneous neural activity of the sensorimotor network in
      patients with DM1. Compared to healthy controls, patients with DM1 showed higher
      PSD responses in the orbitofrontal cortex, parahippocampus and basal ganglia
      (corrected P < 0.05). Patients with DM1 showed higher PSD responses in white
      matter structures associated with motor function (corrected P < 0.05).
      Furthermore, correlation analysis indicated that the brain regions showing PSD
      differences were correlated with measures of motor performance (P < 0.05). In
      gray matter, our findings suggest that motor disability in DM1 is not an isolated
      deterioration of the motor power but a multimodal dysfunction that also involves
      the visual system. In addition, the widespread PSD alteration in white matter
      structures suggest that motor deficits in DM1 involve motor movement structures
      as well as structures important for its coordination and regulation.

PMID- 29343752
TI  - Counting Caenorhabditis elegans: Protocol Optimization and Applications for
      Population Growth and Toxicity Studies in Liquid Medium.
AB  - The nematode Caenorhabditis elegans is used extensively in molecular,
      toxicological and genetics research. However, standardized methods for counting
      nematodes in liquid culture do not exist despite the wide use of nematodes and
      need for accurate measurements. Herein, we provide a simple and affordable
      counting protocol developed to maximize count accuracy and minimize variability
      in liquid nematode culture. Sources of variability in the counting process were
      identified and tested in 14 separate experiments. Three variables resulted in
      significant effects on nematode count: shaking of the culture, priming of pipette
      tips, and sampling location within a microcentrifuge tube. Between-operator
      variability did not have a statistically significant effect on counts, even among
      differently-skilled operators. The protocol was used to assess population growth
      rates of nematodes in two different but common liquid growth media: axenic
      modified Caenorhabditis elegans Habitation and Reproduction medium (mCeHR) and S
      basal complete. In mCeHR, nematode populations doubled daily for 10 d. S-basal
      complete populations initially doubled every 12 h, but slowed within 7 d. We also
      detected a statistically significant difference between embryo-to-hatchling
      incubation period of 5 d in mCeHR compared to 4 d in S-basal complete. The
      developed counting method for Caenorhabditis elegans reduces variability and
      allows for rigorous and reliable experimentation.

PMID- 29343753
TI  - Procalcitonin as a Biomarker for Malignant Cerebral Edema in Massive Cerebral
      Infarction.
AB  - The objective of this study is to explore whether procalcitonin (PCT) can serve
      as an early biomarker of malignant cerebral edema in patients with massive
      cerebral infarction (MCI). Ninety-three patients with acute MCI were divided into
      death or survival groups based on whether they died or survived within 1 week of
      cerebral herniation. Differences in laboratory parameters between these two
      groups were analyzed by univariate analysis, followed by multivariate logistic
      regression analyses if the influencing factors were significantly different.
      Compared with the survival group, the patients in the death group had a larger
      cerebral infarct area, higher body temperature, neutrophil counts, PCT level, and
      neuron-specific enolase (NSE) level within 48 h of onset. Multivariate logistic
      regression analyses revealed an odds ratio (OR) of 1.830 or 1.235 for PCT and
      neutrophil counts respectively, suggesting that PCT and neutrophil counts are two
      independent risk factors for death in MCI. The area under receiver operating
      characteristic (ROC) curve was 0.754 for PCT, larger than that for neutrophil
      counts. Thus, both serum PCT levels and neutrophil counts can be used as
      biomarkers to predict malignant cerebral edema at the early stages after MCI, but
      PCT levels are superior predictors of malignant cerebral edema.

PMID- 29343754
TI  - Development and validation of a brief diabetic foot ulceration risk checklist
      among diabetic patients: a multicenter longitudinal study in China.
AB  - The study aims to develop and assess and validate a brief diabetic foot
      ulceration risk checklist among diabetic patients through a longitudinal study.
      Patients who had diabetes mellitus and had no foot ulceration and severe
      systematic disorders were recruited from eleven tertiary hospitals in nine
      provinces or municipalities of China. Internal consistency reliability, construct
      validity, concurrent validity, item property, and measurement invariance of the
      tool were assessed. The predictive capability of the tool was validated by the
      follow-up data using the receiver operating characteristic curve. At baseline,
      477 valid cases were collected. Twelve items were remained after initial
      selection. Cronbach's alpha was 0.56. Confirmatory factor analysis showed that
      the model had acceptable goodness-of-fit yet local dependency between two items.
      Item response theory showed that most items had acceptable discrimination and
      difficulty parameters. Differential item functioning showed that tool had
      measurement invariance. 278 were followed up one year after the baseline. Follow
      up showed that one-year incidence of ulceration among the patients was 3.6%, and
      the area under the receiver operating characteristic curve was 0.77 (95%
      confidence interval: 0.61-0.93). The cut-off point of the tool was 4, when
      sensitivity and specificity were 0.62 and 0.75 respectively. The checklist has
      good psychometric properties according to mixed evidences from classical and
      modern test theory, and has good predictive capability.

PMID- 29343755
TI  - Significantly High Modulation Efficiency of Compact Graphene Modulator Based on
      Silicon Waveguide.
AB  - We theoretically and experimentally demonstrate a significantly large modulation
      efficiency of a compact graphene modulator based on a silicon waveguide using the
      electro refractive effect of graphene. The modulation modes of electro-absorption
      and electro-refractive can be switched with different applied voltages. A high
      extinction ratio of 25 dB is achieved in the electro-absorption modulation mode
      with a driving voltage range of 0 V to 1 V. For electro-refractive modulation,
      the driving voltage ranges from 1 V to 3 V with a 185-pm spectrum shift. The
      modulation efficiency of 1.29 V . mm with a 40-MUm interaction length is two
      orders of magnitude higher than that of the first reported graphene phase
      modulator. The realisation of phase and intensity modulation with graphene based
      on a silicon waveguide heralds its potential application in optical communication
      and optical interconnection systems.

PMID- 29343756
TI  - Radiological and clinical differences among three assisted technologies in
      pedicle screw fixation of adult degenerative scoliosis.
AB  - The purpose of this study was to compare the clinical and radiological
      differences among three advanced guided technologies in adult degenerative
      scoliosis. A total of 1012 pedicle screws were inserted in 83 patients using a
      spine robot (group A), 886 screws were implanted in 75 patients using a drill
      guide template (group B), and 1276 screws were inserted in 109 patients using CT
      based navigation (group C). Screw positions were evaluated using postoperative CT
      scans according to the Gertzbein and Robbins classification. Other relevant data
      were also collected. Perfect pedicle screw insertion (Grade A) accuracy in groups
      A, B, and C was 91.3%, 81.3%, and 84.1%, respectively. Clinically acceptable
      accuracy of screw implantation (Grades A + B) respectively was 96.0%, 90.6%, and
      93.0%. Statistical analysis showed the perfect and clinically acceptable accuracy
      in group A was significant different compared with groups B and C. Group A
      exhibited the lowest intra-op radiation dose and group B showed the shortest
      surgical time compared with the other two groups. Robotic-assisted technology
      demonstrated significantly higher accuracy than the drill guide template or CT
      based navigation systems for difficult screw implantations in adult degenerative
      scoliosis and reduced the intra-op radiation dose, although it failed to reduce
      surgery time.

PMID- 29343757
TI  - The early conversion of deep-sea wood falls into chemosynthetic hotspots revealed
      by in situ monitoring.
AB  - Wood debris on the ocean floor harbor flourishing communities, which include
      invertebrate taxa thriving in sulfide-rich habitats belonging to hydrothermal
      vent and methane seep deep-sea lineages. The formation of sulfidic niches from
      digested wood material produced by woodborers has been known for a long time, but
      the temporal dynamics and sulfide ranges encountered on wood falls remains
      unknown. Here, we show that wood falls are converted into sulfidic hotpots,
      before the colonization by xylophagaid bivalves. Less than a month after
      immersion at a depth of 520 m in oxygenated seawater the sulfide concentration
      increased to millimolar levels inside immersed logs. From in situ experiments
      combining high-frequency chemical and video monitoring, we document the rapid
      development of a microbial sulfur biofilm at the surface of wood. These findings
      highlight the fact that sulfide is initially produced from the labile components
      of wood and supports chemosynthesis as an early pathway of energy transfer to
      deep-sea wood colonists, as suggested by recent aquarium studies. The study
      furthermore reveals that woodborers promote sulfide-oxidation at the periphery of
      their burrows, thus, not only facilitating the development of sulfidic zones in
      the surrounding of degraded wood falls, but also governing sulfur-cycling within
      the wood matrix.

PMID- 29343758
TI  - Electronic Properties of Synthetic Shrimp Pathogens-derived DNA Schottky Diodes.
AB  - The exciting discovery of the semiconducting-like properties of deoxyribonucleic
      acid (DNA) and its potential applications in molecular genetics and diagnostics
      in recent times has resulted in a paradigm shift in biophysics research. Recent
      studies in our laboratory provide a platform towards detecting charge transfer
      mechanism and understanding the electronic properties of DNA based on the
      sequence-specific electronic response, which can be applied as an alternative to
      identify or detect DNA. In this study, we demonstrate a novel method for
      identification of DNA from different shrimp viruses and bacteria using electronic
      properties of DNA obtained from both negative and positive bias regions in
      current-voltage (I-V) profiles. Characteristic electronic properties were
      calculated and used for quantification and further understanding in the
      identification process. Aquaculture in shrimp industry is a fast-growing food
      sector throughout the world. However, shrimp culture in many Asian countries
      faced a huge economic loss due to disease outbreaks. Scientists have been using
      specific established methods for detecting shrimp infection, but those methods do
      have their significant drawbacks due to many inherent factors. As such, we
      believe that this simple, rapid, sensitive and cost-effective tool can be used
      for detection and identification of DNA from different shrimp viruses and
      bacteria.

PMID- 29343759
TI  - Incorporation of iloprost in phospholipase-resistant phospholipid scaffold
      enhances its barrier protective effects on pulmonary endothelium.
AB  - Correction of barrier dysfunction and inflammation in acute lung injury (ALI)
      represents an important problem. Previous studies demonstrate barrier-protective
      and anti-inflammatory effects of bioactive lipid prostacyclin and its stable
      analog iloprost (ILO). We generated a phospholipase resistant synthetic
      phospholipid with iloprost attached at the sn-2 position (ILO-PC) and
      investigated its biological effects. In comparison to free ILO, ILO-PC caused
      sustained endothelial cell (EC) barrier enhancement, linked to more prolonged
      activation of Rap1 and Rac1 GTPases and their cytoskeletal and cell junction
      effectors: cortactin, PAK1, p120-catenin and VE-cadherin. ILO and ILO-PC equally
      efficiently suppressed acute, Rho GTPase-dependent EC hyper-permeability caused
      by thrombin. However, ILO-PC exhibited more sustained barrier-protective and anti
      inflammatory effects in the model of chronic EC dysfunction caused by bacterial
      wall lipopolysacharide (LPS). ILO-PC was also more potent inhibitor of NFkappaB
      signaling and lung vascular leak in the murine model of LPS-induced ALI.
      Treatment with ILO-PC showed more efficient ALI recovery over 3 days after LPS
      challenge than free ILO. In conclusion, this study describes a novel synthetic
      phospholipid with barrier-enhancing and anti-inflammatory properties superior to
      existing prostacyclin analogs, which may be used as a prototype for future
      development of more efficient treatment for ALI and other vascular leak
      syndromes.

PMID- 29343760
TI  - Large-scale semi-arid afforestation can enhance precipitation and carbon
      sequestration potential.
AB  - Afforestation is an important approach to mitigate global warming. Its complex
      interactions with the climate system, however, makes it controversial.
      Afforestation is expected to be effective in the tropics where biogeochemical and
      biogeophysical effects act in concert; however, its potential in the large semi
      arid regions remains insufficiently explored. Here, we use a Global Climate Model
      to provide a process-based demonstration that implementing measured
      characteristics of a successful semi-arid afforestation system (2000 ha, ~300 mm
      mean annual precipitation) over large areas (~200 million ha) of similar
      precipitation levels in the Sahel and North Australia leads to the weakening and
      shifting of regional low-level jets, enhancing moisture penetration and
      precipitation (+0.8 +/- 0.1 mm d-1 over the Sahel and +0.4 +/- 0.1 mm d-1 over
      North Australia), influencing areas larger than the original afforestation. These
      effects are associated with increasing root depth and surface roughness and with
      decreasing albedo. This results in enhanced evapotranspiration, surface cooling
      and the modification of the latitudinal temperature gradient. It is estimated
      that the carbon sequestration potential of such large-scale semi-arid
      afforestation can be on the order of ~10% of the global carbon sink of the land
      biosphere and would overwhelm any biogeophysical warming effects within ~6 years.

PMID- 29343761
TI  - A high throughput approach for the generation of orthogonally interacting protein
      pairs.
AB  - In contrast to the nearly error-free self-assembly of protein architectures in
      nature, artificial assembly of protein complexes with pre-defined structure and
      function in vitro is still challenging. To mimic nature's strategy to construct
      pre-defined three-dimensional protein architectures, highly specific protein
      protein interacting pairs are needed. Here we report an effort to create an
      orthogonally interacting protein pair from its parental pair using a bacteria
      based in vivo directed evolution strategy. This high throughput approach features
      a combination of a negative and a positive selection. The newly developed
      negative selection from this work was used to remove any protein mutants that
      retain effective interaction with their parents. The positive selection was used
      to identify mutant pairs that can engage in effective mutual interaction. By
      using the cohesin-dockerin protein pair that is responsible for the self-assembly
      of cellulosome as a model system, we demonstrated that a protein pair that is
      orthogonal to its parent pair could be readily generated using our strategy. This
      approach could open new avenues to a wide range of protein-based assembly, such
      as biocatalysis or nanomaterials, with pre-determined architecture and
      potentially novel functions and properties.

PMID- 29343762
TI  - Mercury sodium exospheric emission as a proxy for solar perturbations transit.
AB  - The first evidence at Mercury of direct relation between ICME transit and Na
      exosphere dynamics is presented, suggesting that Na emission, observed from
      ground, could be a proxy of planetary space weather at Mercury. The link existing
      between the dayside exosphere Na patterns and the solar wind-magnetosphere
      surface interactions is investigated. This goal is pursued by analyzing the Na
      intensity hourly images, as observed by the ground-based THEMIS solar telescope
      during 10 selected periods between 2012 and 2013 (with seeing, sigma < = 2"),
      when also MESSENGER data were available. Frequently, two-peak patterns of
      variable intensity are observed, located at high latitudes in both hemispheres.
      Occasionally, Na signal is instead diffused above the sub-solar region. We
      compare these different patterns with the in-situ time profiles of proton fluxes
      and magnetic field data from MESSENGER. Among these 10 cases, only in one
      occasion the Na signal is diffused above the subsolar region, when the MESSENGER
      data detect the transit of two ICMEs. The selected cases suggest that the Na
      emission patterns are well related to the solar wind conditions at Mercury.
      Hence, the exospheric Na emission patterns, observed from ground, could be
      considered as a 'natural monitor' of solar disturbances when transiting near
      Mercury.

PMID- 29343763
TI  - Association of S100B polymorphisms and serum S100B with risk of ischemic stroke
      in a Chinese population.
AB  - The levels of serum S100B were elevated in patients with ischemic stroke (IS),
      which may be a novel biomarker for diagnosing IS. The aim of this study was to
      investigate the association of S100B polymorphisms and serum S100B with IS risk.
      We genotyped the S100B polymorphisms rs9722, rs9984765, rs2839356, rs1051169 and
      rs2186358 in 396 IS patients and 398 controls using polymerase chain reaction
      single base extension (SBE-PCR). Serum S100B levels were measured by enzyme
      linked immunosorbent assay (ELISA). Rs9722 was associated with an increased risk
      of IS (AA vs. GG: adjusted OR = 2.172, 95% CI, 1.175-4.014, P = 0.013; dominant:
      adjusted OR = 1.507, 95% CI, 1.071-2.123, P = 0.019; recessive: adjusted OR =
      1.846, 95% CI, 1.025-3.323, P = 0.041; additive: adjusted OR=1.371, 95% CI, 1.109
      1.694, P = 0.003). The A-C-C-C-A haplotype was associated with an increased risk
      of IS (OR = 1.325, 95% CI, 1.035-1.696, P = 0.025). In addition, individuals
      carrying the rs9722 GA/AA genotypes had a higher serum S100B compared with the
      rs9722 GG genotype in IS patients (P = 0.018). Our results suggest that the S100B
      gene rs9722 polymorphism may contribute to the susceptibility of IS, probably by
      promoting the expression of serum S100B.

PMID- 29343765
TI  - Regulation of Signaling Pathways Involved in the Anti-proliferative and Apoptosis
      inducing Effects of M22 against Non-small Cell Lung Adenocarcinoma A549 Cells.
AB  - The compound 29-(4-methylpiperazine)-luepol (M22), a novel derivative of lupeol
      has shown anti-proliferative effects against the human non-small cell lung cancer
      A549 cell line. M22 showed significant anti-proliferative activity at 6.80 MUM
      and increased accumulation of G1 cells and effectively suppressed expression of
      the G1 arrest-related genes cyclins D1 and E1, CDK2 and CDC25A. This was further
      confirmed by Western blotting demonstrating decreased cyclin D1 and CDC25A
      protein levels. Furthermore, M22 caused induction of apoptosis that downregulated
      the anti-apoptotic BCL-2 gene and increased expression of BAX, CASP3 and CASP9 as
      well as the APAF1 gene. The effect of caspase-induced apoptosis was confirmed by
      an increase in reactive oxygen species (ROS), loss of mitochondrial membrane
      potential (MMP). Taken together, our findings indicated that M22 possessed potent
      anti-proliferative and apoptotic activities.

PMID- 29343766
TI  - Sudden sensory neural hearing loss is not predictive of myocardial infarction: A
      longitudinal follow-up study using a national sample cohort.
AB  - The aim of this study was to evaluate the risk of myocardial infarction (MI) in
      SSNHL subjects with differently matched control groups. The Korean Health
      Insurance Review and Assessment Service - National Sample Cohort recruited
      subjects from 2002 to 2013. We used two study designs. In study I, we matched
      4,467 SSNHL participants with a control group (17,868 subjects with no history of
      SSNHL) based on demographic factors (age, sex, income, and region of residence)
      and medical history (diabetes, dyslipidemia, and hypertension). In study II, we
      matched 4,467 SSNHL participants with a control group based on only demographic
      factors. The crude (simple) and adjusted hazard ratios (HRs) of SSNHL with MI
      were analyzed using the Cox-proportional hazard model. In study I, SSNHL was not
      associated with increased risk of MI. However, in study II, SSNHL was associated
      with increased risk of MI (adjusted HR = 1.39 95% CI = 1.00-1.93, P = 0.048). The
      SSNHL group did not exhibit increased risk of MI when compared to the control
      group matched by both demographic factors and medical history. However, compared
      to the control group not matched by medical history, the relative risk of MI was
      increased in the SSNHL group.

PMID- 29343767
TI  - Blockade of TRPV1 Inhibits Methamphetamine-induced Rewarding Effects.
AB  - Methamphetamine (MAP) is the most widely used psychostimulant in the world, but
      the exact mechanisms underlying MAP addiction are not yet fully understood.
      Recent studies have identified the distribution of TRPV1 in several brain regions
      that are related to drug addiction, including nucleus accumbens (NAc) and dorsal
      striatum (DSt). In the present study, we performed conditioned place preference
      (CPP) and self-administration tests to examine the effects of capsazepine (CPZ)
      and SB366791 (SB) on MAP reward. We found that both CPZ and SB significantly
      inhibited MAP-induced CPP and self-administration; in contrast, TRPV1 knock-out
      (KO) mice did not develop MAP-induced CPP. Real-time RT-PCR, Western blot and
      quantitative autoradiographic tests showed up-regulation of TRPV1 mRNA and
      protein expression in the NAc and/or DSt regions of mice exhibiting MAP-induced
      CPP. In addition, an in vivo microdialysis experiment showed that CPZ
      dramatically reduced dopamine (DA) levels in the NAc region of MAP-treated mice.
      Furthermore, attenuated dopamine transporter (DAT) binding levels in the NAc and
      DSt regions of MAP-induced CPP mice were reversed by CPZ. Together, these data
      suggest that TRPV1 plays an important role in MAP reward via the modulation of DA
      release and DAT density, thereby providing a novel therapeutic target for MAP
      addiction.

PMID- 29343768
TI  - Broadband Asymmetric Light Transmission at Metal/Dielectric Composite Grating.
AB  - Optical diode-like effect has sparked growing interest in recent years due to its
      potential applications in integrated photonic systems. In this paper, we propose
      and numerically demonstrate a new type of easy-processing metal/dielectric
      cylinder composite grating on semi-sphere substrate, which can achieve high
      contrast asymmetric transmission of unpolarized light for the sum of all
      diffraction modes in the entire visible region, and effectively guide the
      diffraction light transmitting out the substrate. The asymmetric light
      transmission (ALT) ratio is larger than 2 dB in the waveband from 380 nm to 780
      nm and the maximum ALT ratio can reach to 13 dB at specified wavelengths. The
      thorough theoretical research reveals that the proposed metal/dielectric pillar
      composite grating structure, together with the substrate, can effectively excite
      localized surface plasmonic resonance (LSPR) effect and waveguide mode (WGM), and
      enlarge the diffraction difference between forward and backward transmission
      spaces, including both number of diffraction orders and diffraction efficiency,
      thus resulting in high-contrast broadband ALT phenomenon. In particular, lowering
      the symmetry of the grating can achieve polarization-dependent ALT. Such a type
      of easy-processing ALT device with high performance for both polarized and
      unpolarized light can be regarded as suitable candidates in practical
      applications.

PMID- 29343764
TI  - Genome-wide association study in 79,366 European-ancestry individuals informs the
      genetic architecture of 25-hydroxyvitamin D levels.
AB  - Vitamin D is a steroid hormone precursor that is associated with a range of human
      traits and diseases. Previous GWAS of serum 25-hydroxyvitamin D concentrations
      have identified four genome-wide significant loci (GC, NADSYN1/DHCR7, CYP2R1,
      CYP24A1). In this study, we expand the previous SUNLIGHT Consortium GWAS
      discovery sample size from 16,125 to 79,366 (all European descent). This larger
      GWAS yields two additional loci harboring genome-wide significant variants (P =
      4.7*10-9 at rs8018720 in SEC23A, and P = 1.9*10-14 at rs10745742 in AMDHD1). The
      overall estimate of heritability of 25-hydroxyvitamin D serum concentrations
      attributable to GWAS common SNPs is 7.5%, with statistically significant loci
      explaining 38% of this total. Further investigation identifies signal enrichment
      in immune and hematopoietic tissues, and clustering with autoimmune diseases in
      cell-type-specific analysis. Larger studies are required to identify additional
      common SNPs, and to explore the role of rare or structural variants and gene-gene
      interactions in the heritability of circulating 25-hydroxyvitamin D levels.

PMID- 29343769
TI  - CKAMP44 modulates integration of visual inputs in the lateral geniculate nucleus.
AB  - Relay neurons in the dorsal lateral geniculate nucleus (dLGN) receive excitatory
      inputs from retinal ganglion cells (RGCs). Retinogeniculate synapses are
      characterized by a prominent short-term depression of AMPA receptor (AMPAR)
      mediated currents, but the underlying mechanisms and its function for visual
      integration are not known. Here we identify CKAMP44 as a crucial auxiliary
      subunit of AMPARs in dLGN relay neurons, where it increases AMPAR-mediated
      current amplitudes and modulates gating of AMPARs. Importantly, CKAMP44 is
      responsible for the distinctive short-term depression in retinogeniculate
      synapses by reducing the rate of recovery from desensitization of AMPARs. Genetic
      deletion of CKAMP44 strongly reduces synaptic short-term depression, which leads
      to increased spike probability of relay neurons when activated with high
      frequency inputs from retinogeniculate synapses. Finally, in vivo recordings
      reveal augmented ON- and OFF-responses of dLGN neurons in CKAMP44 knockout
      (CKAMP44-/-) mice, demonstrating the importance of CKAMP44 for modulating
      synaptic short-term depression and visual input integration.

PMID- 29343770
TI  - Reconstructing the gradient source position from steady-state fluxes to small
      receptors.
AB  - Recovering the position of a source from the fluxes of diffusing particles
      through small receptors allows a biological cell to determine its relative
      position, spatial localization and guide it to a final target. However, how a
      source can be recovered from point fluxes remains unclear. Using the Narrow
      Escape approach for an open domain, we compute the diffusion fluxes of Brownian
      particles generated by a steady-state gradient from a single source through small
      holes distributed on a surface in two dimensions. We find that the location of a
      source can be recovered when there are at least 3 receptors and the source is
      positioned no further than 10 cell radii away, but this condition is not
      necessary in a narrow strip. The present approach provides a computational basis
      for the first step of direction sensing of a gradient at a single cell level.

PMID- 29343772
TI  - Shape-matching soft mechanical metamaterials.
AB  - Architectured materials with rationally designed geometries could be used to
      create mechanical metamaterials with unprecedented or rare properties and
      functionalities. Here, we introduce "shape-matching" metamaterials where the
      geometry of cellular structures comprising auxetic and conventional unit cells is
      designed so as to achieve a pre-defined shape upon deformation. We used
      computational models to forward-map the space of planar shapes to the space of
      geometrical designs. The validity of the underlying computational models was
      first demonstrated by comparing their predictions with experimental observations
      on specimens fabricated with indirect additive manufacturing. The forward-maps
      were then used to devise the geometry of cellular structures that approximate the
      arbitrary shapes described by random Fourier's series. Finally, we show that the
      presented metamaterials could match the contours of three real objects including
      a scapula model, a pumpkin, and a Delft Blue pottery piece. Shape-matching
      materials have potential applications in soft robotics and wearable (medical)
      devices.

PMID- 29343771
TI  - Magnetoencephalographic Correlates of Perceptual State During Auditory
      Bistability.
AB  - Bistability occurs when two alternative percepts can be derived from the same
      physical stimulus. To identify the neural correlates of specific subjective
      experiences we used a bistable auditory stimulus and determined whether the two
      perceptual states could be distinguished electrophysiologically. Fourteen
      participants underwent magnetoencephalography while reporting their perceptual
      experience while listening to a continuous bistable stream of auditory tones.
      Participants reported bistability with a similar overall proportion of the two
      alternative percepts (52% vs 48%). At the individual level, sensor space
      electrophysiological discrimination between the percepts was possible in 9/14
      participants with canonical variate analysis (CVA) or linear support vector
      machine (SVM) analysis over space and time dimensions. Classification was
      possible in 14/14 subjects with non-linear SVM. Similar effects were noted in an
      unconstrained source space CVA analysis (classifying 10/14 participants), linear
      SVM (classifying 9/14 subjects) and non-linear SVM (classifiying 13/14
      participants). Source space analysis restricted to a priori ROIs showed
      discrimination was possible in the right and left auditory cortex with each
      classification approach but in the right intraparietal sulcus this was only
      apparent with non-linear SVM and only in a minority of particpants.
      Magnetoencephalography can be used to objectively classify auditory experiences
      from individual subjects.

PMID- 29343773
TI  - Mitochondrial Mutations in Cholestatic Liver Disease with Biliary Atresia.
AB  - Biliary atresia (BA) results in severe bile blockage and is caused by the absence
      of extrahepatic ducts. Even after successful hepatic portoenterostomy, a
      considerable number of patients are likely to show progressive deterioration in
      liver function. Recent studies show that mutations in protein-coding
      mitochondrial DNA (mtDNA) genes and/or mitochondrial genes in nuclear DNA (nDNA)
      are associated with hepatocellular dysfunction. This observation led us to
      investigate whether hepatic dysfunctions in BA is genetically associated with
      mtDNA mutations. We sequenced the mtDNA protein-coding genes in 14 liver
      specimens from 14 patients with BA and 5 liver specimens from 5 patients with
      choledochal cyst using next-generation sequencing. We found 34 common non
      synonymous variations in mtDNA protein-coding genes in all patients examined. A
      systematic 3D structural analysis revealed the presence of several single
      nucleotide polymorphism-like mutations in critical regions of complexes I to V,
      that are involved in subunit assembly, proton-pumping activity, and/or
      supercomplex formation. The parameters of chronic hepatic injury and liver
      dysfunction in BA patients were also significantly correlated with the extent of
      hepatic failure, suggesting that the mtDNA mutations may aggravate hepatopathy.
      Therefore, mitochondrial mutations may underlie the pathological mechanisms
      associated with BA.

PMID- 29343774
TI  - An improved method of crafting a multi-electrode spiral cuff for the selective.
AB  - This article reviews an improved methodology and technology for crafting a multi
      electrode spiral cuff for the selective activation of nerve fibres in particular
      superficial regions of a peripheral nerve. The analysis, structural and
      mechanical properties of the spot welds used for the interconnections between the
      stimulating electrodes and stainless-steel lead wires are presented. The cuff
      consisted of 33 platinum electrodes embedded within a self-curling 17-mm-long
      silicone spiral sheet with a nominal internal diameter of 2.5 mm. The weld was
      analyzed using scanning electron microscopy and nanohardness tests, while the
      interconnection was investigated using destructive load tests. The functionality
      of the cuff was tested in an isolated porcine vagus nerve. The results of the
      scanning electron microscopy show good alloying and none of the typical welding
      defects that occur between the wire and the platinum foil. The results of the
      destructive load tests show that the breaking loads were between 3.22 and 5 N.
      The results of the nanohardness testing show that the hardness of the weld was
      different for the particular sites on the weld sample. Finally, the results of
      the functional testing show that for different stimulation intensities both the
      compound action potential deflection and the shape are modulated.

PMID- 29343775
TI  - Impact of Concurrent Genomic Alterations Detected by Comprehensive Genomic
      Sequencing on Clinical Outcomes in East-Asian Patients with EGFR-Mutated Lung
      Adenocarcinoma.
AB  - Next-generation sequencing (NGS) has enabled comprehensive detection of genomic
      alterations in lung cancer. Ethnic differences may play a critical role in the
      efficacy of targeted therapies. The aim of this study was to identify and compare
      genomic alterations of lung adenocarcinoma between Japanese patients and the
      Cancer Genome Atlas (TCGA), which majority of patients are from the US. We also
      aimed to examine prognostic impact of additional genomic alterations in patients
      harboring EGFR mutations. Genomic alterations were determined in Japanese
      patients with lung adenocarcinoma (N = 100) using NGS-based sequencing of 415
      known cancer genes, and correlated with clinical outcome. EGFR active mutations,
      i.e., those involving exon 19 deletion or an L858R point mutation, were seen in
      43% of patients. Some differences in driver gene mutation prevalence were
      observed between the Japanese cohort described in the present study and the TCGA.
      Japanese cohort had significantly more genomic alterations in cell cycle pathway,
      i.e., CDKN2B and RB1 than TCGA. Concurrent mutations, in genes such as CDKN2B or
      RB1, were associated with worse clinical outcome in patients with EGFR active
      mutations. Our data support the utility of comprehensive sequencing to detect
      concurrent genomic variations that may affect clinical outcomes in this disease.

PMID- 29343776
TI  - Critical Shear Stress is Associated with Diabetic Kidney Disease in Patients with
      Type 2 Diabetes.
AB  - Critical shear stress (CSS, mPa) is an index of red blood cell (RBC)
      aggregability, defined as the minimal shear stress required to disperse RBC
      aggregates. This study aimed to investigate the association between CSS and the
      risk of diabetic kidney disease (DKD). A total of 421 (mean age, 58.1 +/- 11.5
      years; male, 250) individuals with T2DM were enrolled and divided into three
      groups according to CSS level. CSS was measured using a transient microfluidic
      technique. DKD was defined as a glomerular filtration rate (GFR) <60 ml/min/1.73
      m2 or a urine albumin-to-creatinine ratio (uACR) >=30 mg/g. CSS was significantly
      higher in patients with DKD than in those without (317.43 +/- 125.11 vs 385.22 +/
      182.89, p < 0.001). Compared to the lowest CSS tertile, the highest CSS tertile
      was independently associated with the risk of DKD after adjusting for age, sex,
      duration of diabetes, presence of hypertension and haemoglobin. The cut-off value
      of CSS for DKD was approximately 310 mPa. These results suggest that
      haemorheologic changes may contribute to DKD, and further prospective studies are
      warranted to determine the role of CSS as a DKD screening tool.

PMID- 29343777
TI  - The hidden cost of using low-resolution concentration data in the estimation of
      NH3 dry deposition fluxes.
AB  - Long-term monitoring stations for atmospheric pollutants are often equipped with
      low-resolution concentration samplers. In this study, we analyse the errors
      associated with using monthly average ammonia concentrations as input variables
      for bidirectional biosphere-atmosphere exchange models, which are commonly used
      to estimate dry deposition fluxes. Previous studies often failed to account for a
      potential correlation between ammonia exchange velocities and ambient
      concentrations. We formally derive the exact magnitude of these errors from
      statistical considerations and propose a correction scheme based on parallel
      measurements using high-frequency analysers. In case studies using both modelled
      and measured ammonia concentrations and micrometeorological drivers from sites
      with varying pollution levels, we were able to substantially reduce bias in the
      predicted ammonia fluxes. Neglecting to account for these errors can, in some
      cases, lead to significantly biased deposition estimates compared to using high
      frequency instrumentation or corrected averaging strategies. Our study presents a
      first step towards a unified correction scheme for data from nation-wide air
      pollutant monitoring networks to be used in chemical transport and air quality
      models.

PMID- 29343778
TI  - Fumarate-based metal-organic frameworks as a new platform for highly selective
      removal of fluoride from brick tea.
AB  - Adsorption and removal of fluoride from brick tea is very important but
      challenging. In this work, two fumarate-based metal-organic frameworks (MOFs)
      were synthesized for the selective removal of fluoride from brick tea infusion.
      MOFs were examined for adsorption time, effect of dose, and uptake capacity at
      different initial concentrations and temperatures. Remarkably, over 80% fluoride
      removal was achieved by MOF-801 within 5 min at room temperature, while no
      significant adsorption occurred for the catechins and caffeine in the brick tea
      infusion. Further, with the use of the Langmuir equation, the maximum fluoride
      uptake capacity for the nontoxic calcium fumarate (CaFu) MOF was calculated to be
      as high as 166.11 mg g-1 at 373 K. As observed from FTIR, EDX and XPS results,
      hydroxyl group in MOFs were substituted by fluoride. This work demonstrates that
      the novel fumarate-based MOFs are promising materials for the selective removal
      of fluoride from brick tea infusion.

PMID- 29343780
TI  - Waste Windshield-Derived Silicon/Carbon Nanocomposites as High-Performance
      Lithium-Ion Battery Anodes.
AB  - Silicon has emerged as the most promising high-capacity material for lithium-ion
      batteries. Waste glass can be a potential low cost and environmentally benign
      silica resource enabling production of nanosized silicon at the industry level.
      Windshields are generally made of laminated glass comprising two separate glass
      bonded together with a layer of polyvinyl butyral sandwiched between them.
      Herein, silicon/carbon nanocomposites are fabricated from windshields for the
      first time via magnesiothermic reduction and facile carbonization process using
      both waste glass and polyvinyl butyral as silica and carbon sources,
      respectively. High purity reduced silicon has unique 3-dimensional nanostructure
      with large surface area. Furthermore, the incorporation of carbon in silicon
      enable to retain the composite anodes highly conductive and mechanically robust,
      thus providing enhanced cycle stability.

PMID- 29343779
TI  - Characterization of signaling pathways regulating the expression of pro
      inflammatory long form thymic stromal lymphopoietin upon human metapneumovirus
      infection.
AB  - Thymic stromal lymphopoietin (TSLP) is associated with several allergic diseases
      including asthma. Two isoforms of TSLP exist in humans, a long form (lfTSLP) and
      a short form (sfTSLP), displaying distinct immunological functions. Recently,
      TSLP was found to be upregulated in human airway cells upon human metapneumovirus
      (hMPV) infection, yet it remains unclear if the two isoforms are regulated
      differently during hMPV infection. Importantly, the molecular mechanisms
      underlying hMPV-mediated TSLP induction remain undescribed. In this study, we
      characterized the expression and regulation of TSLP in hMPV-infected human airway
      cells. We demonstrated that hMPV strongly induced the expression of pro
      inflammatory lfTSLP in human airway epithelial cells and lung fibroblasts.
      Further, knockdown of pattern recognition receptors retinoic acid-inducible gene
      I (RIG-I) or Toll-like receptor 3 (TLR3), as well as downstream signal
      transducers, abrogated hMPV-mediated lfTSLP induction. Importantly, silencing of
      TANK-binding kinase 1 (TBK1) also impaired hMPV-mediated lfTSLP induction, which
      could be attributed to compromised NF-kappaB activation. Overall, these results
      suggest that TBK1 may be instrumental for hMPV-mediated activation of NF-kappaB
      downstream RIG-I and TLR3, leading to a specific induction of lfTSLP in hMPV
      infected human airway cells.

PMID- 29343781
TI  - Ocular and Clinical Characteristics Associated with the Extent of Posterior
      Lamina Cribrosa Curve in Normal Tension Glaucoma.
AB  - Although normal-tension glaucoma (NTG) is pathogenetically heterogenous, there
      have been few attempts to subclassify NTG patients according to the mechanism and
      anatomy of optic nerve damage. This cross-sectional study was performed to
      investigate differences in the clinical and ocular characteristics between NTG
      patient groups stratified according to the degree of posterior lamina cribrosa
      (LC) curve which was assessed by calculating LC curvature index (LCCI). A total
      of 101 eyes of 101 treatment naive NTG patients were included. The optic nerve
      head was imaged using enhanced-depth-imaging spectral-domain optical coherence
      tomography in three horizontal B-scan images in each eye. The patients were
      divided into two groups based on the magnitude of LCCI using a cutoff of known
      upper 95 percentile value in healthy subjects: a steeply curved LC group (Group
      1, 75 eyes, 74.3%) and a relatively flat LC group (Group 2, 26 eyes, 25.7%). NTG
      eyes with relatively flat LC had lower intraocular pressure, and were associated
      with greater parapapillary structural alternation and systemic risk factors.
      These data suggest that assessment of LC morphology may help clinicians seek
      additional risk factors and make inferences about the mechanism of optic nerve
      damage in individual patients.

PMID- 29343783
TI  - The Hessian Blob Algorithm: Precise Particle Detection in Atomic Force Microscopy
      Imagery.
AB  - Imaging by atomic force microscopy (AFM) offers high-resolution descriptions of
      many biological systems; however, regardless of resolution, conclusions drawn
      from AFM images are only as robust as the analysis leading to those conclusions.
      Vital to the analysis of biomolecules in AFM imagery is the initial detection of
      individual particles from large-scale images. Threshold and watershed algorithms
      are conventional for automatic particle detection but demand manual image
      preprocessing and produce particle boundaries which deform as a function of user
      defined parameters, producing imprecise results subject to bias. Here, we
      introduce the Hessian blob to address these shortcomings. Combining a scale-space
      framework with measures of local image curvature, the Hessian blob formally
      defines particle centers and their boundaries, both to subpixel precision.
      Resulting particle boundaries are independent of user defined parameters, with no
      image preprocessing required. We demonstrate through direct comparison that the
      Hessian blob algorithm more accurately detects biomolecules than conventional AFM
      particle detection techniques. Furthermore, the algorithm proves largely
      insensitive to common imaging artifacts and noise, delivering a stable framework
      for particle analysis in AFM.

PMID- 29343782
TI  - Protein phosphatase 5 regulates titin phosphorylation and function at a sarcomere
      associated mechanosensor complex in cardiomyocytes.
AB  - Serine/threonine protein phosphatase 5 (PP5) is ubiquitously expressed in
      eukaryotic cells; however, its function in cardiomyocytes is unknown. Under basal
      conditions, PP5 is autoinhibited, but enzymatic activity rises upon binding of
      specific factors, such as the chaperone Hsp90. Here we show that PP5 binds and
      dephosphorylates the elastic N2B-unique sequence (N2Bus) of titin in
      cardiomyocytes. Using various binding and phosphorylation tests, cell-culture
      manipulation, and transgenic mouse hearts, we demonstrate that PP5 associates
      with N2Bus in vitro and in sarcomeres and is antagonistic to several protein
      kinases, which phosphorylate N2Bus and lower titin-based passive tension. PP5 is
      pathologically elevated and likely contributes to hypo-phosphorylation of N2Bus
      in failing human hearts. Furthermore, Hsp90-activated PP5 interacts with
      components of a sarcomeric, N2Bus-associated, mechanosensor complex, and blocks
      mitogen-activated protein-kinase signaling in this complex. Our work establishes
      PP5 as a compartmentalized, well-controlled phosphatase in cardiomyocytes, which
      regulates titin properties and kinase signaling at the myofilaments.

PMID- 29343784
TI  - Tensile stress effect on epitaxial BiFeO3 thin film grown on KTaO3.
AB  - Comprehensive crystal structural study is performed for BiFeO3 (BFO) film grown
      on KTaO3 (KTO) substrate using transmission electron microscopy (TEM) and x-ray
      diffraction (XRD). Nano-beam electron diffraction (NBED) combined with structure
      factor calculation and high resolution TEM images clearly reveal that the crystal
      structure within BFO thin film is rhombohedral BFO, i.e., bulk BFO phase.
      Epitaxial relationship found by NBED indicates the BFO film grows in a manner
      that minimizes lattice mismatch with KTO. It further suggests BFO film is under
      slight biaxial tensile stress (~0.35%) along in-plane direction. XRD reveals BFO
      lattice is under compressive stress (~1.6%), along out-of-plane direction as a
      result of the biaxial tensile strain applied along in-plane direction. This leads
      to Poisson's ratio of ~0.68. In addition, we demonstrate (1) why hexagonal
      notation rather than pseudocubic one is required for accurate BFO phase
      evaluation and (2) a new XRD method that shows how rhombohedral BFO can readily
      be identified among other phases by measuring a rhombohedral specific Bragg's
      reflection.

PMID- 29343785
TI  - A patient-specific lumped-parameter model of coronary circulation.
AB  - A new lumped-parameter model for coronary hemodynamics is developed. This model
      is developed for the whole coronary network based on CT scans of a patient
      specific geometry including the right coronary tree, which is absent in many
      previous mathematical models. The model adopts the structured tree model boundary
      conditions similar to the work of Olufsen et al., thus avoiding the necessity of
      invasive perfusion measurements. In addition, we also incorporated the effects of
      the head loss at the two inlets of the large coronary arteries for the first
      time. The head loss could explain the phenomenon of a sudden increase of the
      resistance at the inlet of coronary vessel. The estimated blood pressure and flow
      rate results from the model agree well with the clinical measurements. The
      computed impedances also match the experimental perfusion measurement. The
      effects of coronary arterial stenosis are considered and the fractional flow
      reserve and relative flow in the coronary vessels for a stenotic vessel computed
      in this model show good agreement with published experimental data. It is
      believed that the approach could be readily translated to clinical practice to
      facilitate real time clinical diagnosis.

PMID- 29343786
TI  - AlGaInP Red LEDs with Hollow Hemispherical Polystyrene Arrays.
AB  - A hollow hemispherical polystyrene (HHPS) was fabricated to reduce total internal
      reflection in AlGaInP-based LEDs. At an injection current of 350 mA, the external
      quantum efficiencies of LED-I, LED-II, LED-III, and LED-IV are 20.92%, 24.65%,
      27.28%, and 33.77% and the wall-plug efficiencies are 17.11%, 20%, 22.5%, and
      27.33%, respectively. The enhanced performance is attributed to the light output
      power enhancement through the surface roughness, microlens-liked PS hemisphere,
      and scatter-liked HHPS array. In this paper, the rigorous coupled wave analysis
      (RCWA) numerical method was also conducted to demonstrate the HHPS array
      effectively enlarge the effective light cone.

PMID- 29343787
TI  - Author Correction: Comparison of bacterial microbiota of the predatory mite
      Neoseiulus cucumeris (Acari: Phytoseiidae) and its factitious prey Tyrophagus
      putrescentiae (Acari: Acaridae).
AB  - A correction to this article has been published and is linked from the HTML
      version of this paper. The error has been fixed in the paper.

PMID- 29343788
TI  - Multiple losses of photosynthesis and convergent reductive genome evolution in
      the colourless green algae Prototheca.
AB  - Autotrophic eukaryotes have evolved by the endosymbiotic uptake of photosynthetic
      organisms. Interestingly, many algae and plants have secondarily lost the
      photosynthetic activity despite its great advantages. Prototheca and
      Helicosporidium are non-photosynthetic green algae possessing colourless
      plastids. The plastid genomes of Prototheca wickerhamii and Helicosporidium sp.
      are highly reduced owing to the elimination of genes related to photosynthesis.
      To gain further insight into the reductive genome evolution during the shift from
      a photosynthetic to a heterotrophic lifestyle, we sequenced the plastid and
      nuclear genomes of two Prototheca species, P. cutis JCM 15793 and P. stagnora JCM
      9641, and performed comparative genome analyses among trebouxiophytes. Our
      phylogenetic analyses using plastid- and nucleus-encoded proteins strongly
      suggest that independent losses of photosynthesis have occurred at least three
      times in the clade of Prototheca and Helicosporidium. Conserved gene content
      among these non-photosynthetic lineages suggests that the plastid and nuclear
      genomes have convergently eliminated a similar set of photosynthesis-related
      genes. Other than the photosynthetic genes, significant gene loss and gain were
      not observed in Prototheca compared to its closest photosynthetic relative
      Auxenochlorella. Although it remains unclear why loss of photosynthesis occurred
      in Prototheca, the mixotrophic capability of trebouxiophytes likely made it
      possible to eliminate photosynthesis.

PMID- 29343789
TI  - Three-dimensional migration behavior of juvenile salmonids in reservoirs and near
      dams.
AB  - To acquire 3-D tracking data on juvenile salmonids, Juvenile Salmon Acoustic
      Telemetry System (JSATS) cabled hydrophone arrays were deployed in the forebays
      of two dams on the Snake River and at a mid-reach reservoir between the dams. The
      depth distributions of fish were estimated by statistical analyses performed on
      large 3-D tracking data sets from ~33,500 individual acoustic tagged yearling and
      subyearling Chinook salmon and juvenile steelhead at the two dams in 2012 and
      subyearling Chinook salmon at the two dams and the mid-reach reservoir in 2013.
      This research investigated the correlation between vertical migration behavior
      and passage routes. The depth distributions of fish within the forebays of the
      dams were significantly different from fish passing the mid-reach reservoir. Fish
      residing deeper in the forebay tended to pass the dam using deeper powerhouse
      routes. This difference in depth distributions indicated that the depth
      distribution of fish at the mid-reach reservoir was not related to behaviors of
      fish passing through certain routes of the adjacent dams. For fish that were
      detected deeper than 17.5 m in the forebays, the probability of powerhouse
      passage (i.e., turbine) increased significantly. Another important finding was
      the variation in depth distributions during dam passage associated with the diel
      period, especially the crepuscular periods.

PMID- 29343790
TI  - Interference experiment with asymmetric double slit by using 1.2-MV field
      emission transmission electron microscope.
AB  - Advanced electron microscopy technologies have made it possible to perform
      precise double-slit interference experiments. We used a 1.2-MV field emission
      electron microscope providing coherent electron waves and a direct detection
      camera system enabling single-electron detections at a sub-second exposure time.
      We developed a method to perform the interference experiment by using an
      asymmetric double-slit fabricated by a focused ion beam instrument and by
      operating the microscope under a "pre-Fraunhofer" condition, different from the
      Fraunhofer condition of conventional double-slit experiments. Here, pre
      Fraunhofer condition means that each single-slit observation was performed under
      the Fraunhofer condition, while the double-slit observations were performed under
      the Fresnel condition. The interference experiments with each single slit and
      with the asymmetric double slit were carried out under two different electron
      dose conditions: high-dose for calculation of electron probability distribution
      and low-dose for each single electron distribution. Finally, we exemplified the
      distribution of single electrons by color-coding according to the above three
      types of experiments as a composite image.

PMID- 29343791
TI  - Single plasmid systems for inducible dual protein expression and for CRISPR
      Cas9/CRISPRi gene regulation in lactic acid bacterium Lactococcus lactis.
AB  - Lactococcus lactis is a food-grade lactic acid bacterium that is used in the
      dairy industry as a cell factory and as a host for recombinant protein
      expression. The nisin-controlled inducible expression (NICE) system is frequently
      applied in L. lactis; however new tools for its genetic modification are highly
      desirable. In this work NICE was adapted for dual protein expression. Plasmid
      pNZDual, that contains two nisin promoters and multiple cloning sites (MCSs), and
      pNZPolycist, that contains a single nisin promoter and two MCSs separated by the
      ribosome binding site, were constructed. Genes for the infrared fluorescent
      protein and for the human IgG-binding DARPin were cloned in all possible
      combinations to assess the protein yield. The dual promoter plasmid pNZDual
      enabled balanced expression of the two model proteins. It was exploited for the
      development of a single-plasmid inducible CRISPR-Cas9 system (pNZCRISPR) by using
      a nisin promoter, first to drive Cas9 expression and, secondly, to drive single
      guide RNA transcription. sgRNAs against htrA and ermR directed Cas9 against
      genomic or plasmid DNA and caused changes in bacterial growth and survival.
      Replacing Cas9 by dCas9 enabled CRISPR interference-mediated silencing of the upp
      gene. The present study introduces a new series of plasmids for advanced genetic
      modification of lactic acid bacterium L. lactis.

PMID- 29343792
TI  - Prebiotic formation of cyclic dipeptides under potentially early Earth
      conditions.
AB  - Cyclic dipeptides, also known as 2,5-diketopiperazines (DKPs), represent the
      simplest peptides that were first completely characterized. DKPs can catalyze the
      chiral selection of reactions and are considered as peptide precursors. The
      origin of biochemical chirality and synthesis of peptides remains abstruse
      problem believed to be essential precondition to origin of life. Therefore, it is
      reasonable to believe that the DKPs could have played a key role in the origin of
      life. How the formation of the DKPs through the condensation of unprotected amino
      acids in simulated prebiotic conditions has been unclear. Herein, it was found
      that cyclo-Pro-Pro could be formed directly from unprotected proline in the
      aqueous solution of trimetaphosphate (P3m) under mild condition with the yield up
      to 97%. Other amino acids were found to form proline-containing DKPs under the
      same conditions in spite of lower yield. During the formation process of these
      DKPs, P3m promotes the formation of linear dipeptides in the first step of the
      mechanism. The above findings are helpful and significant for understanding the
      formation of DKPs in the process of chemical evolution of life.

PMID- 29343793
TI  - nNOS-positive minor-branches of the dorsal penile nerves is associated with
      erectile function in the bilateral cavernous injury model of rats.
AB  - The changes in neuronal nitric oxide synthases (nNOS) in the dorsal penile nerves
      (DPNs) are consistent with cavernous nerve (CN) injury in rat models. However,
      the anatomical relationship and morphological changes between the minor branches
      of the DPNs and the CNs after injury have never been clearly explored. There were
      forty 12 week old male Sprague-Dawley rats receiving bilateral cavernous nerve
      injury (BCNI). Erectile function of intracavernous pressure and mean arterial
      pressure were measured. The histology and ultrastructure with H&E stain, Masson's
      trichrome stain and immunohistochemical stains were applied on the examination of
      CNs and DPNs. We demonstrated communicating nerve branches between the DPNs and
      the CNs in rats. The greatest damage and lowest erectile function were seen in
      the 14th day and partially recovered in the 28th day after BCNI. The nNOS
      positive DPN minor branches' number was significantly correlated with erectile
      function. The sub-analysis of the number of nNOS positive DPN minor branches also
      matched with the time course of the erectile function after BCNI. We suggest the
      regeneration of the DPNs minor branches would ameliorate the erectile function in
      BCNI rats.

PMID- 29343794
TI  - Bone regeneration using a porcine bone substitute collagen composite in vitro and
      in vivo.
AB  - The biocharacteristics of xenogeneic grafts make them a possible substitute for
      autogenous bone grafts in dental bone graft procedures. This study aimed to
      develop a novel porcine graft with collagen capable of generating new bone in
      bone defects via osteoconduction over 8 weeks of healing and to compare it with a
      porcine graft. The porcine collagen graft was made to undergo a cell viability
      test (MTT) and alkaline phosphatase assay (ALP). The surgical procedure was
      performed in 20 male adult New Zealand white rabbits. Four calvarial critical
      size defects of 6 mm in diameter were prepared in each rabbit. The upper left
      defect was filled with a porcine graft of 500-1000 MUm, the upper right with a
      porcine collagen graft, the lower left with hydroxyapatite/beta-tricalcium
      phosphate and the lower right served as the control without any filling material.
      The rabbits were divided and sacrificed at 2, 4, 6 and 8 weeks after surgery.
      Histological and micro-CT scan results showed that the performance of the porcine
      collagen graft is superior for regenerating new bone. Porcine collagen graft
      showed cell viability and osteoblast-like cell differentiation in vitro. The
      results indicate that porcine collagen graft is a potential bone substitute for
      clinical application.

PMID- 29343795
TI  - Recurrent wheezing in neonatal pneumonia is associated with combined infection
      with Respiratory Syncytial Virus and Staphylococcus aureus or Klebsiella
      pneumoniae.
AB  - Both viral and bacterial infections can be associated with wheezing episodes in
      children; however, information regarding combined infections with both viral and
      bacterial pathogens in full term neonates is limited. We sought to investigate
      the effects of viral-bacterial codetection on pneumonia severity and recurrent
      wheezing. A retrospective cohort study was conducted on neonates admitted to our
      hospital with pneumonia from 2009 to 2015. Of 606 total cases, 341 were diagnosed
      with RSV only, and 265 were diagnosed with both RSV and a potential bacterial
      pathogen. The leading four species of bacteria codetected with RSV were
      Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus and Enterobacter
      cloacae. Neonates with RSV and a potential bacterial pathogen were significantly
      more likely to have worse symptoms, higher C-reactive protein values and more
      abnormal chest x-ray manifestations with Bonferroni correction for multiple
      comparisons (P < 0.01). On Cox regression analysis, an increased risk of
      recurrent wheezing was found for neonates positive for RSV-Staphylococcus aureus
      and RSV-Klebsiella pneumoniae. Our findings indicate that the combination of
      bacteria and RSV in the neonatal airway is associated with more serious clinical
      characteristics. The presence of RSV and Staphylococcus aureus or Klebsiella
      pneumoniae may provide predictive markers for wheeze.

PMID- 29343796
TI  - Integrated climate-chemical indicators of diffuse pollution from land to water.
AB  - Management of agricultural diffuse pollution to water remains a challenge and is
      influenced by the complex interactions of rainfall-runoff pathways, soil and
      nutrient management, agricultural landscape heterogeneity and biogeochemical
      cycling in receiving water bodies. Amplified cycles of weather can also influence
      nutrient loss to water although they are less considered in policy reviews. Here,
      we present the development of climate-chemical indicators of diffuse pollution in
      highly monitored catchments in Western Europe. Specifically, we investigated the
      influences and relationships between weather processes amplified by the North
      Atlantic Oscillation during a sharp upward trend (2010-2016) and the patterns of
      diffuse nitrate and phosphorus pollution in rivers. On an annual scale, we found
      correlations between local catchment-scale nutrient concentrations in rivers and
      the influence of larger, oceanic-scale climate patterns defined by the intensity
      of the North Atlantic Oscillation. These influences were catchment-specific
      showing positive, negative or no correlation according to a typology. Upward
      trends in these decadal oscillations may override positive benefits of local
      management in some years or indicate greater benefits in other years. Developing
      integrated climate-chemical indicators into catchment monitoring indicators will
      provide a new and important contribution to water quality management objectives.

PMID- 29343797
TI  - Artificial Intelligence Estimation of Carotid-Femoral Pulse Wave Velocity using
      Carotid Waveform.
AB  - In this article, we offer an artificial intelligence method to estimate the
      carotid-femoral Pulse Wave Velocity (PWV) non-invasively from one uncalibrated
      carotid waveform measured by tonometry and few routine clinical variables. Since
      the signal processing inputs to this machine learning algorithm are sensor
      agnostic, the presented method can accompany any medical instrument that provides
      a calibrated or uncalibrated carotid pressure waveform. Our results show that,
      for an unseen hold back test set population in the age range of 20 to 69, our
      model can estimate PWV with a Root-Mean-Square Error (RMSE) of 1.12 m/sec
      compared to the reference method. The results convey the fact that this model is
      a reliable surrogate of PWV. Our study also showed that estimated PWV was
      significantly associated with an increased risk of CVDs.

PMID- 29343799
TI  - Publisher Correction: Bacillus SEVA siblings: A Golden Gate-based toolbox to
      create personalized integrative vectors for Bacillus subtilis.
AB  - A correction to this article has been published and is linked from the HTML
      version of this paper. The error has been fixed in the paper.

PMID- 29343798
TI  - Structural and functional insights into S-thiolation of human serum albumins.
AB  - Human serum albumin (HSA) is the most abundant serum protein, contributing to the
      maintenance of redox balance in the extracellular fluids. One single free
      cysteine residue at position 34 is believed to be a target of oxidation. However,
      the molecular details and functions of oxidized HSAs remain obscure. Here we
      analyzed serum samples from normal subjects and hyperlipidemia patients and
      observed an enhanced S-thiolation of HSA in the hyperlipidemia patients as
      compared to the control individuals. Both cysteine and homocysteine were
      identified as the low molecular weight thiols bound to the HSAs. Intriguingly, S
      thiolations were observed not only at Cys34, but also at multiple cysteine
      residues in the disulfide bonds of HSA. When the serum albumins from genetically
      modified mice that exhibit high levels of total homocysteine in serum were
      analyzed, we observed an enhanced S-homocysteinylation at multiple cysteine
      residues. In addition, the cysteine residues in the disulfide bonds were also
      thiolated in recombinant HSA that had been treated with the disulfide molecules.
      These findings and the result that S-homocysteinylation mediated increased
      surface hydrophobicity and ligand binding activity of HSA offer new insights into
      structural and functional alternation of serum albumins via S-thiolation.

PMID- 29343800
TI  - Faecal shedding of rotavirus vaccine in Chinese children after vaccination with
      Lanzhou lamb rotavirus vaccine.
AB  - Lanzhou lamb rotavirus vaccine (LLR) is an oral live attenuated vaccine first
      licensed in China in 2000. To date, > 60 million doses of LLR have been
      distributed to children. However, very little is known about faecal shedding of
      LLR in children. Therefore, faecal samples (n = 1,184) were collected from 114
      children for 15 days post-vaccination in September-November 2011/2012. Faecal
      shedding and viral loads were determined by an enzyme immunoassay kit (EIA) and
      real-time RT-PCR. The complete genome was sequenced and the vaccine strain was
      isolated by culture in MA104 cells. Approximately 14.0% (16/114) of children had
      rotavirus-positive samples by EIA for at least 1 day post-vaccination. Viral
      loads in EIA-positive samples ranged from < 1.0 * 103 to 1.9 * 108 copies/g.
      Faecal shedding occurred as early as post-vaccination day 2 and as late as post
      vaccination day 13 and peaked on post-vaccination day 5-10. One LLR strain was
      isolated by culture in MA104 cells. Sequence analysis showed 99% identity with
      LLR prototype strain. Faecal shedding of LLR in stool is common within 15 days of
      LLR vaccination, indicating vaccine strains can replicate in human enteric
      tissues.

PMID- 29343801
TI  - Dictionary learning-based reverberation removal enables depth-resolved
      photoacoustic microscopy of cortical microvasculature in the mouse brain.
AB  - Photoacoustic microscopy (PAM) capitalizes on the optical absorption of blood
      hemoglobin to enable label-free high-contrast imaging of the cerebral
      microvasculature in vivo. Although time-resolved ultrasonic detection equips PAM
      with depth-sectioning capability, most of the data at depths are often obscured
      by acoustic reverberant artifacts from superficial cortical layers and thus
      unusable. In this paper, we present a first-of-a-kind dictionary learning
      algorithm to remove the reverberant signal while preserving underlying
      microvascular anatomy. This algorithm was validated in vitro, using dyed beads
      embedded in an optically transparent polydimethylsiloxane phantom. Subsequently,
      we demonstrated in the live mouse brain that the algorithm can suppress
      reverberant artifacts by 21.0 +/- 5.4 dB, enabling depth-resolved PAM up to 500
      um from the brain surface.

PMID- 29343802
TI  - Loss induced coherent combining in InP-Si3N4 hybrid platform.
AB  - Loss, as a time-reversed counterpart of gain, can also be used to control lasing
      in an optical system with coupled cavities. In this study, by manipulating mirror
      losses at different output ports of coupled Fabry-Perot cavities, an integrated
      coherently combined laser system is proposed and experimentally demonstrated in
      the InP-Si3N4 hybrid platform. Two InP-based reflective semiconductor amplifiers
      are coherently combined through an adiabatic 50:50 directional coupler in silicon
      nitride. The combining efficiency is ~92% at ~2* threshold. The novel system not
      only realizes the miniaturization of coherent laser beam combining but also
      provides a chip-scale platform to study the coherent coupling between coupled
      laser cavities.

PMID- 29343803
TI  - Targeted next generation sequencing in a young population with suspected
      inherited malignant cardiac arrhythmias.
AB  - Aborted sudden cardiac death in the young often is due to inherited heart
      disease. However, the clinical phenotype in these patients is not always evident.
      The aim of this study was to identify pathogenic molecular genetic variants in a
      population with suspected inherited cardiac arrhythmias. Eligible patients were
      admitted to Aarhus University Hospital, Denmark during the period 1999-2013 with
      arrhythmias assumed caused by a hereditary heart disease, and in whom no genotype
      had been established. We used the Danish national pacemaker and ICD registry to
      identify this cohort. One third (24/80) of the study population had first-line
      genetic testing with a targeted next-generation sequencing (NGS) panel, and two
      third (56/80) of the study population had second-line genetic testing with NGS
      where prior Sanger sequencing did not reveal a causative variant. Variants were
      assessed according to the American College of Medical Genetics and Genomics
      (ACMG) guidelines. We included 80 patients. Median age (IQR) was 38 (28-43)
      years, 54 (68%) were males. First-line genetic testing identified a genetic
      variant in 33% (8/24) of the cases and second-line genetic testing revealed a
      variant in 20% (11/56) of the cases. Eleven variants were considered pathogenic,
      three likely pathogenic and 10 were variants of unknown significance (VUS).
      Seventeen variants were very rare with a minor allele frequency (MAF) <=0.02% in
      all population databases used in the study. Molecular genetic testing of patients
      with suspected inherited cardiac arrhythmias with NGS identifies a molecular
      genetic cause in a significant proportion of patients.

PMID- 29343804
TI  - Compound heterozygous SPATA5 variants in four families and functional studies of
      SPATA5 deficiency.
AB  - Variants in the SPATA5 gene were recently described in a cohort of patients with
      global developmental delay, sensorineural hearing loss, seizures, cortical visual
      impairment and microcephaly. SPATA5 protein localizes predominantly in the
      mitochondria and is proposed to be involved in mitochondrial function and brain
      developmental processes. However no functional studies have been performed. This
      study describes five patients with psychomotor developmental delay, microcephaly,
      epilepsy and hearing impairment, who were thought clinically to have a
      mitochondrial disease with subsequent whole-exome sequencing analysis detecting
      compound heterozygous variants in the SPATA5 gene. A summary of clinical data of
      all the SPATA5 patients reported in the literature confirms the characteristic
      phenotype. To assess SPATA5's role in mitochondrial dynamics, functional studies
      were performed on rat cortical neurons. SPATA5-deficient neurons had a
      significant imbalance in the mitochondrial fusion-fission rate, impaired energy
      production and short axons. In conclusion, SPATA5 protein has an important role
      in mitochondrial dynamics and axonal growth. Biallelic variants in the SPATA5
      gene can affect mitochondria in cortical neurons and should be considered in
      patients with a neurodegenerative disorder and/or with clinical presentation
      resembling a mitochondrial disorder.

PMID- 29343806
TI  - Effect of light-delignification on mechanical, hydrophobic, and thermal
      properties of high-strength molded fiber materials.
AB  - This study developed a high-strength molded fiber material (HMFM) using pulp
      fibers, which could be a good substitute for plastic and solid wood materials.
      The surface composition, microstructure and thermal properties of HMFM were
      investigated by XPS, SEM and DSC, respectively. The SEM observations showed that
      the obvious adhesive substances and agglomeration appeared among fibers, and the
      inter-fiber contact area and binding tightness increased after the light
      delignification. The XPS examination showed that the oxygen-rich composition on
      the outer surface of HMFM were reduced, and the outer surface coverage of lignin
      increased from 70.05% to 90.15% after the light-delignification. The DSC
      observation showed that the thermal stability of HMFM decreased, the temperature
      for the maximum rate of mass loss decreased from 370  degrees C to 345.6  degrees
      C, and the enthalpy value required for decomposition was reduced from 110.8 J/g
      to 68.0 J/g after the light-delignification. The mechanical and hydrophobic
      properties of HMFM were obviously improved after the light-delignification. When
      the content of lignin decreased from 24.9% to 11.45%, the density of HMFM
      increased by 6.0%, the tensile strength increased by 22.0%, the bending strength
      increased by 23.9%, and the water contact angle increased from 64.3 degrees -72.7
      degrees  to 80.8 degrees -84.3 degrees .

PMID- 29343805
TI  - Biallelic variants in KIF14 cause intellectual disability with microcephaly.
AB  - Kinesin proteins are critical for various cellular functions such as
      intracellular transport and cell division, and many members of the family have
      been linked to monogenic disorders and cancer. We report eight individuals with
      intellectual disability and microcephaly from four unrelated families with
      parental consanguinity. In the affected individuals of each family, homozygosity
      for likely pathogenic variants in KIF14 were detected; two loss-of-function
      (p.Asn83Ilefs*3 and p.Ser1478fs), and two missense substitutions (p.Ser841Phe and
      p.Gly459Arg). KIF14 is a mitotic motor protein that is required for spindle
      localization of the mitotic citron rho-interacting kinase, CIT, also mutated in
      microcephaly. Our results demonstrate the involvement of KIF14 in development and
      reveal a wide phenotypic variability ranging from fetal lethality to moderate
      developmental delay and microcephaly.

PMID- 29343807
TI  - House dust mite induced allergic airway disease is attenuated in CD11ccreIL
      4Ralpha-/l degrees x mice.
AB  - The precise mechanisms leading to development of T helper type (Th)2-driven
      allergic responses are unknown. We aimed to determine how IL-4 receptor alpha (IL
      4Ralpha) signaling on CD11c+ cells influences allergen-induced Th2 responses in
      mice. CD11ccreIL-4Ralpha-/l degrees x mice, deficient in IL-4Ralpha on dendritic
      cells and alveolar macrophages, were compared to IL-4Ralpha-/l degrees x
      littermate controls in models of allergic airway disease induced by OVA/alum, OVA
      alone or house dust mite. Cytokine responses, eosinophil and neutrophil
      infiltration into the lungs, airway hyperreactivity and mucus hypersecretion were
      evaluated after allergen challenge. In the OVA/alum model, CD11ccreIL-4Ralpha
      /lox mice had similar airway hyperreactivity, eosinophil infiltration, Th2-type
      cytokine production and mucus hypersecretion to littermate controls. When alum
      was omitted during sensitization, CD11ccreIL-4Ralpha-/lox mice had similar airway
      hyperreactivity and mucus secretion but reduced Th2-type cytokine production and
      eosinophils, suggesting alum overrides the requirement for IL-4Ralpha signaling
      on CD11c+ cells in enhancing Th2-type responses. In the house dust mite model,
      CD11ccreIL-4Ralpha-/lox mice showed similar mucus secretion, but reduced Th2
      responses, eosinophils, neutrophils and airway hyperreactivity, unlike previously
      tested LysMcreIL-4Ralpha-/lox mice, which lack IL-4Ralpha on alveolar macrophages
      but not on dendritic cells. Therefore, our results indicate that IL-4Ralpha
      signaling on dendritic cells promotes allergen-induced Th2 responses and
      eosinophil infiltration into the lung.

PMID- 29343808
TI  - Stereotactic topography of the greater and third occipital nerves and its
      clinical implication.
AB  - This study aimed to provide topographic information of the greater occipital
      (GON) and third occipital (3ON) nerves, with the three-dimensional locations of
      their emerging points on the back muscles (60 sides, 30 cadavers) and their
      spatial relationship with muscle layers, using a 3D digitizer (Microscribe G2X,
      Immersion Corp, San Jose CA, USA). With reference to the external occipital
      protuberance (EOP), GON pierced the trapezius at a point 22.6 +/- 7.4 mm lateral
      and 16.3 +/- 5.9 mm inferior and the semispinalis capitis (SSC) at a point 13.1
      +/- 6.0 mm lateral and 27.7 +/- 9.9 mm inferior. With the same reference, 3ON
      pierced, the trapezius at a point 12.9 +/- 9.3 mm lateral and 44.2 +/- 21.4 mm
      inferior, the splenius capitis at a point 10.0 +/- 5.3 mm lateral and 59.2 +/-
      19.8 mm inferior, and SSC at a point 11.5 +/- 9.9 mm lateral and 61.4 +/- 15.3 mm
      inferior. Additionally, GON arose, winding up the obliquus capitis inferior, with
      the winding point located 52.3 +/- 11.7 mm inferior to EOP and 30.2 +/- 8.9 mm
      lateral to the midsagittal line. Knowing the course of GON and 3ON, from their
      emergence between vertebrae to the subcutaneous layer, is necessary for reliable
      nerve detection and precise analgesic injections. Moreover, stereotactic
      measurement using the 3D digitizer seems useful and accurate for neurovascular
      structure study.

PMID- 29343809
TI  - Interaction of smoking and metabolic syndrome in increasing the recurrence risk
      of colorectal cancer in a Chinese male cohort: a retrospective study.
AB  - Whether smoking and metabolic syndrome (MetS) can affect colorectal carcinoma
      (CRC) prognosis remains debatable. Therefore, the present study aimed to examine
      the individual and combined effects of smoking and MetS on the prognosis of
      patients with localized CRC, including stage I to III disease. The relationship
      among smoking status, MetS, and CRC was assessed in 838 Chinese male patients.
      Cox proportional hazards regression analysis was used to evaluate CRC prognosis
      adjusted for clinicopathological variables. Relative excess risk of interaction
      (RERI), attributable proportion (AP), and synergy index (SI) were used to
      evaluate additive interactions between smoking and MetS. The presence of MetS was
      an independent risk factor for low rates of recurrence-free survival (RFS) but
      not for overall survival (OS). However, smoking was independently associated with
      both poor RFS and OS. Furthermore, the recurrence risk for current smokers with
      MetS was 1.62 times as high as the sum of risks in patients exposed to each risk
      factor alone. In conclusion, current smoking habit is a risk factor for both
      recurrence and cancer-specific mortality in CRC patients, while MetS is an
      independent predictor for CRC recurrence. Furthermore, these two factors have an
      additive effect on the recurrence risk of CRC.

PMID- 29343810
TI  - Mitochondrial DNA damage and subsequent activation of Z-DNA binding protein 1
      links oxidative stress to inflammation in epithelial cells.
AB  - This report identifies mitochondrial DNA (mtDNA) as a target and active mediator
      that links low-level oxidative stress to inflammatory response in pulmonary
      epithelial cells. Extrusion of mtDNA into the bronchoalveolar lavage fluid occurs
      as an early event in mice subjected to cigarette smoke injury, concomitantly with
      the depletion of mtDNA in the lung tissue. In cultured lung epithelial cells,
      prolonged, low-level oxidative stress damages the mtDNA, without any detectable
      damage to the nuclear DNA. In turn, cellular depletion of the mtDNA occurs,
      together with a transient remodeling of cellular bioenergetics and morphology -
      all without any detectable impairment in overall cell viability. Damaged mtDNA
      first enters the cytoplasm, where it binds to Z-DNA binding protein 1 (ZBP1) and
      triggers inflammation via the TANK-binding kinase 1 /interferon regulatory factor
      3 signaling pathway. Fragments of the mtDNA are subsequently released into the
      extracellular space via exosomes. MtDNA-containing exosomes are capable of
      inducing an inflammatory response in naive (non-oxidatively stressed) epithelial
      cells. In vivo, administration of isolated mtDNA into the in lungs of naive mice
      induces the production of pro-inflammatory mediators, without histopathologic
      evidence of tissue injury. We propose that mtDNA-specific damage, and subsequent
      activation of the ZBP1 pathway, is a mechanism that links prolonged, low-level
      oxidative stress to autocrine and paracrine inflammation during the early stages
      of inflammatory lung disease.

PMID- 29343812
TI  - High albumin level is a predictor of favorable response to immunotherapy in
      autoimmune encephalitis.
AB  - There is no known biomarker that predicts the response to immune therapy in
      autoimmune synaptic encephalitis. Thus, we investigated serum albumin as a
      prognostic biomarker of early immune therapies in patients with autoimmune
      encephalitis. We enrolled patients who were diagnosed with definite autoimmune
      encephalitis and underwent IVIg treatment at Seoul National University Hospital
      from 2012 to 2017. Patients were dichotomized according to serum albumin prior to
      IVIg administration with a cut-off level of 4.0 g/dL, which was the median value
      of 50% of patients. Seventeen (53.1%) of the 32 patients with definite autoimmune
      encephalitis who received IVIg treatment in our hospital had low serum albumin
      (<4.0 g/dL). The initial disease severity (mRS >= 4) was the sole factor that
      predicted low albumin in autoimmune encephalitis patients using multivariate
      analysis (P = 0.013). The low albumin group exhibited a worse response to immune
      therapy at the third and fourth weeks from IVIg administration (P < 0.01 and P =
      0.012, respectively), and recovery to activities of daily life without assistance
      was faster in the high albumin group (log-rank test for trend, P < 0.01). Our
      study found that pretreatment low serum albumin was a significant indicator of
      autoimmune encephalitis prognosis in the short-term and long-term.

PMID- 29343811
TI  - A procession of metabolic alterations accompanying muscle senescence in Manduca
      sexta.
AB  - Biological aging profoundly impairs muscle function, performance, and metabolism.
      Because the progression of metabolic alterations associated with aging muscle has
      not been chronicled, we tracked the metabolic profiles of flight muscle from
      middle to advanced age in Manduca sexta to identify key molecules during the
      progression of muscle aging, as well as to evaluate the utility of the M. sexta
      system for molecular dissection of muscle aging. We identified a number of
      differences between Diel Time, Sexes, and Muscle Ages, including changes in
      metabolites related to energetics, extracellular matrix turnover, and glutathione
      metabolism. Increased abundances of glycolytic metabolites suggest a shift toward
      increased glycolysis with advancing age, whereas decreased abundances in
      lysolipids and acylcarnitines reflect decreasing beta-oxidation. We also observed
      a shift towards decreased polyamine metabolism with age, which might result in an
      age-related decline in lipid metabolism possibly due to regulation of energy
      metabolism by polyamines. Collectively, our findings demonstrate the feasibility
      of our system and approach and provide a deeper understanding of lepidopteran
      aging. More importantly, the results identify the key altered metabolic pathways
      that collectively contribute to the muscle aging phenotype and thereby improve
      our understanding of muscle senescence.

PMID- 29343813
TI  - The Drosophila Gr28bD product is a non-specific cation channel that can be used
      as a novel thermogenetic tool.
AB  - Extrinsic control of single neurons and neuronal populations is a powerful
      approach for understanding how neural circuits function. Adding new thermogenetic
      tools to existing optogenetic and other forms of intervention will increase the
      complexity of questions that can be addressed. A good candidate for developing
      new thermogenetic tools is the Drosophila gustatory receptor family, which has
      been implicated in high-temperature avoidance behavior. We examined the five
      members of the Gr28b gene cluster for temperature-dependent properties via three
      approaches: biophysical characterization in Xenopus oocytes, functional calcium
      imaging in Drosophila motor neurons, and behavioral assays in adult Drosophila.
      Our results show that Gr28bD expression in Xenopus oocytes produces a non
      specific cationic current that is activated by elevated temperatures. This
      current is non-inactivating and non-voltage dependent. When expressed in
      Drosophila motor neurons, Gr28bD can be used to change the firing pattern of
      individual cells in a temperature-dependent fashion. Finally, we show that pan
      neuronal or motor neuron expression of Gr28bD can be used to alter fruit fly
      behavior with elevated temperatures. Together, these results validate the
      potential of the Gr28bD gene as a founding member of a new class of thermogenetic
      tools.

PMID- 29343814
TI  - Intrinsic apoptotic pathway activation increases response to anti-estrogens in
      luminal breast cancers.
AB  - Estrogen receptor-alpha positive (ERalpha+) breast cancer accounts for
      approximately 70-80% of the nearly 25,0000 new cases of breast cancer diagnosed
      in the US each year. Endocrine-targeted therapies (those that block ERalpha
      activity) serve as the first line of treatment in most cases. Despite the proven
      benefit of endocrine therapies, however, ERalpha+ breast tumors can develop
      resistance to endocrine therapy, causing disease progression or relapse,
      particularly in the metastatic setting. Anti-apoptotic Bcl-2 family proteins
      enhance breast tumor cell survival, often promoting resistance to targeted
      therapies, including endocrine therapies. Herein, we investigated whether
      blockade of anti-apoptotic Bcl-2 family proteins could sensitize luminal breast
      cancers to anti-estrogen treatment. We used long-term estrogen deprivation (LTED)
      of human ERalpha+ breast cancer cell lines, an established model of sustained
      treatment with and acquired resistance to aromatase inhibitors (AIs), in
      combination with Bcl-2/Bcl-xL inhibition (ABT-263), finding that ABT-263 induced
      only limited tumor cell killing in LTED-selected cells in culture and in vivo.
      Interestingly, expression and activity of the Bcl-2-related factor Mcl-1 was
      increased in LTED cells. Genetic Mcl-1 ablation induced apoptosis in LTED
      selected cells, and potently increased their sensitivity to ABT-263. Increased
      expression and activity of Mcl-1 was similarly seen in clinical breast tumor
      specimens treated with AI + the selective estrogen receptor downregulator
      fulvestrant. Delivery of Mcl-1 siRNA loaded into polymeric nanoparticles (MCL1 si
      NPs) decreased Mcl-1 expression in LTED-selected and fulvestrant-treated cells,
      increasing tumor cell death and blocking tumor cell growth. These findings
      suggest that Mcl-1 upregulation in response to anti-estrogen treatment enhances
      tumor cell survival, decreasing response to therapeutic treatments. Therefore,
      strategies blocking Mcl-1 expression or activity used in combination with
      endocrine therapies would enhance tumor cell death.

PMID- 29343816
TI  - Sclerotic bone lesions as a potential imaging biomarker for the diagnosis of
      tuberous sclerosis complex.
AB  - Tuberous-sclerosis-complex (TSC) is associated with a high lifetime risk of
      severe complications. Clinical manifestations are largely variable and diagnosis
      is often missed. Sclerotic-bone-lesions (SBL) could represent a potential imaging
      biomarker for the diagnosis of TSC. In this study, computed tomography (CT) data
      sets of 49 TSC patients (31 females) were included and compared to an age/sex
      matched control group. Imaging features of SBLs included frequency, size and
      location pattern. Sensitivities, specificities and cutoff values for the
      diagnosis of TSC were established for the skull, thorax, and abdomen/pelvis. In
      TSC patients, 3439 SBLs were detected, including 665 skull SBLs, 1426 thoracal
      SBLs and 1348 abdominal/pelvic SBLs. In the matched control-collective, 157 SBLs
      could be found. The frequency of SBLs enabled a reliable differentiation between
      TSC patients and the control collective with the following sensitivities and
      specificities. Skull: >=5 SBLs, 0.783, 1; thorax: >=4 SBLs, 0.967, 0.967;
      abdomen/pelvis: >=5 SBLs: 0.938, 0.906. SBL size was significantly larger
      compared to controls (p < 0.05). Based on the frequency, size and location
      pattern of SBLs TSC can be suspected. SBLs may serve as a potential imaging
      biomarker in the workup of TSC patients.

PMID- 29343815
TI  - MicroRNA-145-5p and microRNA-320a encapsulated in endothelial microparticles
      contribute to the progression of vasculitis in acute Kawasaki Disease.
AB  - Kawasaki Disease (KD) is an acute inflammatory disease that takes the form of
      systemic vasculitis. Endothelial microparticles (EMPs) have been recognized as an
      important transcellular delivery system. We hypothesized whether EMPs are
      involved in vasculitis in acute KD. Fifty patients with acute KD were enrolled,
      divided into two subgroups: those with coronary artery lesions (CAL) (n = 5) and
      those without CAL (NCAL) (n = 45). EMPs were measured using flow cytometry, and
      microRNA (miR) expression profiling was performed by microRNA array. The
      percentage of EMPs in acute KD was significantly higher than in controls (P <
      0.0001). EMPs in patients with CAL rapidly increased after the initial treatment,
      and was significantly higher than those in NCAL (P < 0.001). In patients with
      CAL, we identified 2 specific miRs encapsulated in EMPs, hsa-miR-145-5p and hsa
      miR-320a, which are predicted to affect monocyte function using in silico
      analysis, and were demonstrated to upregulate inflammatory cytokine mRNAs in THP
      1 monocytes. In situ hybridization confirmed that hsa-miR-145-5p was
      preferentially expressed in CAL. EMPs may serve as a sensitive marker for the
      severity of vasculitis in acute KD. Moreover, these 2 specific miRs encapsulated
      in EMPs might be involved in inflammatory cytokine regulation and the
      pathogenesis of vasculitis in acute KD.

PMID- 29343817
TI  - Associations between body mass index and the risk of renal events in patients
      with type 2 diabetes.
AB  - BACKGROUND/OBJECTIVES: We aimed to evaluate the relationship between BMI and the
      risk of renal disease in patients with type 2 diabetes in the Action in Diabetes
      and Vascular Disease: PreterAx and DiamicroN Modified-Release Controlled
      Evaluation (ADVANCE) study. SUBJECTS/METHODS: Participants were divided into six
      baseline BMI categories: <18.5 (underweight, n = 58); >=18.5 to <25 (normal, n =
      2894); >=25 to <30 (overweight, n = 4340); >=30 to <35 (obesity grade 1, n =
      2265); >=35 to <40 (obesity grade 2, n = 744); and >=40 kg/m2 (obesity grade 3, n
      = 294); those underweight were excluded. The composite outcome "major renal
      event" was defined as development of new macroalbuminuria, doubling of
      creatinine, end stage renal disease, or renal death. These outcomes and
      development of new microalbuminuria were considered individually as secondary
      endpoints. RESULTS: During 5-years of follow-up, major renal events occurred in
      487 (4.6%) patients. The risk increased with higher BMI. Multivariable-adjusted
      HRs (95% CIs), compared to normal weight, were: 0.91 (0.72-1.15) for overweight;
      1.03 (0.77-1.37) for obesity grade 1; 1.42 (0.98-2.07) for grade 2; and 2.16
      (1.34-3.48) for grade 3 (p for trend = 0.006). These findings were similar across
      subgroups by randomised interventions (intensive versus standard glucose control
      and perindopril-indapamide versus placebo). Every additional unit of BMI over 25
      kg/m2 increased the risk of major renal events by 4 (1-6)%. Comparable results
      were observed with the risk of secondary endpoints. CONCLUSIONS: Higher BMI is an
      independent predictor of major renal events in patients with type 2 diabetes. Our
      findings encourage weight loss to improve nephroprotection in these patients.

PMID- 29343818
TI  - A surfactant polymer dressing potentiates antimicrobial efficacy in biofilm
      disruption.
AB  - A 100% water-soluble surfactant polymer dressing (SPD) that is bio-compatible and
      non-ionic has been reported to improve wound closure in preliminary clinical
      studies. The mechanism of action of SPD in wound healing remains unclear. Biofilm
      infection is a significant problem that hinders proper wound closure. The
      objective of this study was to characterize the mechanism of action of SPD
      inhibition of bacterial biofilm development. Static biofilms (48 h) of the
      primary wound pathogens Pseudomonas aeruginosa (PA01), Staphylococcus aureus
      (USA300) were grown on polycarbonate membranes and treated with SPD with and
      without antibiotics for an additional 24 h. The standard antibiotics - tobramycin
      (10 MUg/ml) for PA01 and rifampicin (10 MUg/ml) for USA300, were used in these
      studies. Following 24 h treatment with and without antibiotics, the biofilms were
      characterized using scanning electron microscopy (SEM) structural imaging, in
      vitro imaging system (IVIS) proliferation imaging, colony forming units (CFU),
      viability assay, quantitative PCR (qPCR) for virulence gene expression. Because
      SPD is a surfactant based dressing, it potentially has a direct effect on Gram
      negative bacteria such as Pseudomonas primarily due to the lipid-based outer
      membrane of the bacteria. SPD is a surfactant based dressing that has potent anti
      biofilm properties directly or in synergy with antibiotics.

PMID- 29343819
TI  - Effects of silver nanocolloids on plant complex type N-glycans in Oryza sativa
      roots.
AB  - Silver nanomaterials have been mainly developed as antibacterial healthcare
      products worldwide, because of their antibacterial activity. However, there is
      little data regarding the potential risks and effects of large amounts of silver
      nanomaterials on plants. In contrast, N-glycans play important roles in various
      biological phenomena, and their structures and expressions are sensitive to
      ambient environmental changes. Therefore, to assesse the effects of silver
      nanomaterials, we focused on the correlation between N-glycans and the effects of
      silver nanomaterials in plants and analyzed N-glycan structures in Oryza sativa
      seedlings exposed to silver nanocolloids (SNCs). The phenotype analysis showed
      that the shoot was not affected by any SNC concentrations, whereas the high SNC
      exposed root was seriously damaged. Therefore, we performed comparative N-glycan
      analysis of roots. As a result, five of total N-glycans were significantly
      increased in SNC exposed roots, of which one was a free-N-glycan with one beta-N
      acetylglucosamine residue at the reducing end. Our results suggest that the
      transition of plant complex type N-glycans, including free-N-glycans, was caused
      by abnormalities in O. sativa development, and free-N-glycan itself has an
      important role in plant development. This study originally adapted glycome
      transition analysis to environmental toxicology and proposed a new category
      called "Environmental glycobiology".

PMID- 29343820
TI  - Increased left ventricular mass index is present in patients with type 2 diabetes
      without ischemic heart disease.
AB  - Left ventricular mass index (LVMI) increase has been described in hypertension
      (HTN), but less is known about its association with type 2 diabetes (T2DM). As
      these conditions frequently co-exist, we investigated the association of T2DM,
      HTN and both with echocardiographic parameters, and hypothesized that patients
      with both had highest LVMI, followed by patients with only T2DM or HTN. Study
      population included 101 T2DM patients, 62 patients with HTN and no T2DM, and 76
      patients with T2DM and HTN, excluded for ischemic heart disease. Demographic and
      clinical data, biochemical measurements, stress echocardiography, transthoracic
      2D Doppler and tissue Doppler echocardiography were performed. Multivariable
      logistic regression was used to determine the independent association with T2DM.
      Linear regression models and Pearson's correlation were used to assess the
      correlations between LVMI and other parameters. Patients with only T2DM had
      significantly greater LVMI (84.9 +/- 20.3 g/m2) compared to patients with T2DM
      and HTN (77.9 +/- 16 g/m2) and only HTN (69.8 +/- 12.4 g/m2). In multivariate
      logistic regression analysis, T2DM was associated with LVMI (OR 1.033, 95%CI
      1.003-1.065, p = 0.029). A positive correlation of LVMI was found with fasting
      glucose (p < 0.001) and HbA1c (p = 0.0003). Increased LVMI could be a potential,
      pre-symptomatic marker of myocardial structural change in T2DM.

PMID- 29343821
TI  - Focal hyperintensity in the dorsal brain stem of patients with cerebellopontine
      angle tumor: A high-resolution 3 T MRI study.
AB  - Focal hyperintensity (FHI) in the dorsal brain stem on T2-weighted images of
      patients with cerebellopontine angle (CPA) tumor was thought to indicate
      degeneration of the vestibular nucleus and to be specific to vestibular
      schwannoma. The purpose of this study was to evaluate FHI by using high
      resolution 3 Tesla magnetic resonance imaging (3 T MRI) and the relation to
      clinical characteristics. We retrospectively reviewed the clinical data and MRI
      of 45 patients with CPA tumors (34 vestibular schwannomas and 11 other tumors).
      FHI in the dorsal brain stem was found in 25 (55.6%) patients (20 vestibular
      schwannomas and 5 other tumors). For the vestibular schwannomas, the factors
      contributing to positive FHI were age (p = 0.025), max CPA (p =  < 0.001),
      hearing ability (P = 0.005), and canal paresis (p =  < 0.001) in the univariate
      analysis. Multivariate regression analysis showed that max CPA (p = 0.029) was a
      significant factor of positive FHI. In other CPA tumors, these factors were not
      significant predictors. With the use of 3 T MRI, FHI was observed more frequently
      than previously reported. Our results suggest that FHI is not a specific
      indicator of vestibular schwannoma and is related to not only vestibular function
      but also other factors.

PMID- 29343823
TI  - Methods and extractants to evaluate silicon availability for sugarcane.
AB  - The correct evaluation of silicon (Si) availability in different soil types is
      critical in defining the amount of Si to be supplied to crops. This study was
      carried out to evaluate two methods and five chemical Si extractants in clayey,
      sandy-loam, and sandy soils cultivated with sugarcane (Saccharum spp. hybrids).
      Soluble Si was extracted using two extraction methods (conventional and microwave
      oven) and five Si extractants (CaCl2, deionized water, KCl, Na-acetate buffer (pH
      4.0), and acetic acid). No single method and/or extractant adequately estimated
      the Si availability in the soils. Conventional extraction with KCl was no more
      effective than other methods in evaluating Si availability; however, it had less
      variation in estimating soluble Si between soils with different textural classes.
      In the clayey and sandy soils, the Na-acetate buffer (pH 4.0) and acetic acid
      were effective in evaluating the Si availability in the soil regardless of the
      extraction methods. The extraction with acetic acid using the microwave oven,
      however, overestimated the Si availability. In the sandy-loam soil, extraction
      with deionized water using the microwave oven method was more effective in
      estimating the Si availability in the soil than the other extraction methods.

PMID- 29343822
TI  - The MICALs are a Family of F-actin Dismantling Oxidoreductases Conserved from
      Drosophila to Humans.
AB  - Cellular form and function - and thus normal development and physiology - are
      specified via proteins that control the organization and dynamic properties of
      the actin cytoskeleton. Using the Drosophila model, we have recently identified
      an unusual actin regulatory enzyme, Mical, which is directly activated by F-actin
      to selectively post-translationally oxidize and destabilize filaments -
      regulating numerous cellular behaviors. Mical proteins are also present in
      mammals, but their actin regulatory properties, including comparisons among
      different family members, remain poorly defined. We now find that each human
      MICAL family member, MICAL-1, MICAL-2, and MICAL-3, directly induces F-actin
      dismantling and controls F-actin-mediated cellular remodeling. Specifically, each
      human MICAL selectively associates with F-actin, which directly induces MICALs
      catalytic activity. We also find that each human MICAL uses an NADPH-dependent
      Redox activity to post-translationally oxidize actin's methionine (M) M44/M47
      residues, directly dismantling filaments and limiting new polymerization. Genetic
      experiments also demonstrate that each human MICAL drives F-actin disassembly in
      vivo, reshaping cells and their membranous extensions. Our results go on to
      reveal that MsrB/SelR reductase enzymes counteract each MICAL's effect on F-actin
      in vitro and in vivo. Collectively, our results therefore define the MICALs as an
      important phylogenetically-conserved family of catalytically-acting F-actin
      disassembly factors.

PMID- 29343824
TI  - Human Papillomavirus Prophylactic Vaccination improves reproductive outcome in
      infertile patients with HPV semen infection: a retrospective study.
AB  - In this study we aimed to evaluate the effect on reproductive outcome of HPV
      vaccination in male subjects of infertile couples with HPV semen infection. In
      this single-center study, we retrospectively enrolled 151 infertile couples with
      detection of HPV in semen, attending our Hospital Unit of Andrology between
      January 2013 and June 2015, counseled to receive adjuvant HPV vaccination.
      Seventy-nine accepted vaccination (vaccine group) whilst 72 did not (control
      group). Our protocol of follow-up, aimed to evaluate HPV viral clearance,
      consisted in semen analysis, INNO-LiPA and FISH for HPV in semen cells after 6
      and 12 months from basal evaluation. Spontaneous pregnancies, miscarriages and
      live births were recorded. Progressive sperm motility and anti-sperm antibodies
      were improved in the vaccine group at both time points (p < 0,05 vs control arm).
      Forty-one pregnancies, 11 in the control group and 30 in the vaccine group, were
      recorded (respectively 15% and 38,9%, p < 0,05) and resulted into 4 deliveries
      and 7 miscarriages (control group) and 29 deliveries and one miscarriage (vaccine
      group, p < 0,05 vs control group). HPV detection on sperms was predictive of
      negative pregnancy outcome. Adjuvant vaccination associated with enhanced HPV
      healing in semen cells and increased rate of natural pregnancies and live births.

PMID- 29343825
TI  - A Survey of Validation Strategies for CRISPR-Cas9 Editing.
AB  - The T7 endonuclease 1 (T7E1) mismatch detection assay is a widely used method for
      evaluating the activity of site-specific nucleases, such as the clustered
      regularly interspaced short palindromic repeats (CRISPR)-Cas9 system. To
      determine the accuracy and sensitivity of this assay, we compared the editing
      estimates derived by the T7E1 assay with that of targeted next-generation
      sequencing (NGS) in pools of edited mammalian cells. Here, we report that
      estimates of nuclease activity determined by T7E1 most often do not accurately
      reflect the activity observed in edited cells. Editing efficiencies of CRISPR
      Cas9 complexes with similar activity by T7E1 can prove dramatically different by
      NGS. Additionally, we compared editing efficiencies predicted by the Tracking of
      Indels by Decomposition (TIDE) assay and the Indel Detection by Amplicon Analysis
      (IDAA) assay to that observed by targeted NGS for both cellular pools and single
      cell derived clones. We show that targeted NGS, TIDE, and IDAA assays predict
      similar editing efficiencies for pools of cells but that TIDE and IDAA can
      miscall alleles in edited clones.

PMID- 29343826
TI  - Mammalian sterile 20 kinase 1 and 2 are important regulators of hematopoietic
      stem cells in stress condition.
AB  - The mammalian Hippo signaling pathway has been implicated in the self-renewal and
      differentiation of stem and progenitor cells. MST1 and MST2 (MST1/2) are core
      serine-threonine kinases in the Hippo signaling pathway, one of which, MST1, has
      been extensively investigated for its role in T cell and myeloid cell function.
      These studies have identified MST1 as a promising therapeutic target in
      immunological disease. However, the roles of MST1/2 in hematopoietic stem cell
      (HSC) function in vivo are not fully understood. Here, we report that mice with a
      conditional deletion of Mst1/2 exhibit impaired hematopoietic stem and progenitor
      cell (HSPC) function under stress condition. Furthermore, Mst1/2 deletion
      markedly altered mature cell output. Therefore, MST1/2 are indispensable for
      maintenance as well as function of stem and progenitor cells under steady state
      conditions and with transplantation stress.

PMID- 29343828
TI  - Widespread persistent changes to temperature extremes occurred earlier than
      predicted.
AB  - A critical question for climate mitigation and adaptation is to understand when
      and where the signal of changes to climate extremes have persistently emerged or
      will emerge from the background noise of climate variability. Here we show
      observational evidence that such persistent changes to temperature extremes have
      already occurred over large parts of the Earth. We further show that climate
      models forced with natural and anthropogenic historical forcings underestimate
      these changes. In particular, persistent changes have emerged in observations
      earlier and over a larger spatial extent than predicted by models. The delayed
      emergence in the models is linked to a combination of simulated change ('signal')
      that is weaker than observed, and simulated variability ('noise') that is greater
      than observed. Over regions where persistent changes had not occurred by the year
      2000, we find that most of the observed signal-to-noise ratios lie within the 16
      84% range of those simulated. Examination of simulations with and without
      anthropogenic forcings provides evidence that the observed changes are more
      likely to be anthropogenic than nature in origin. Our findings suggest that
      further changes to temperature extremes over parts of the Earth are likely to
      occur earlier than projected by the current climate models.

PMID- 29343827
TI  - Targeted NUDT5 inhibitors block hormone signaling in breast cancer cells.
AB  - With a diverse network of substrates, NUDIX hydrolases have emerged as a key
      family of nucleotide-metabolizing enzymes. NUDT5 (also called NUDIX5) has been
      implicated in ADP-ribose and 8-oxo-guanine metabolism and was recently identified
      as a rheostat of hormone-dependent gene regulation and proliferation in breast
      cancer cells. Here, we further elucidate the physiological relevance of known
      NUDT5 substrates and underscore the biological requirement for NUDT5 in gene
      regulation and proliferation of breast cancer cells. We confirm the involvement
      of NUDT5 in ADP-ribose metabolism and dissociate a relationship to oxidized
      nucleotide sanitation. Furthermore, we identify potent NUDT5 inhibitors, which
      are optimized to promote maximal NUDT5 cellular target engagement by CETSA. Lead
      compound, TH5427, blocks progestin-dependent, PAR-derived nuclear ATP synthesis
      and subsequent chromatin remodeling, gene regulation and proliferation in breast
      cancer cells. We herein present TH5427 as a promising, targeted inhibitor that
      can be used to further study NUDT5 activity and ADP-ribose metabolism.

PMID- 29343830
TI  - Biological rejuvenation of iron oxides in bioturbated marine sediments.
AB  - The biogeochemical cycle of iron is intricately linked to numerous element
      cycles. Although biological processes that catalyze the reductive side of the
      iron cycle are established, little is known about microbial oxidative processes
      on iron cycling in sedimentary environments-resulting in the formation of iron
      oxides. Here we show that a potential source of sedimentary iron oxides
      originates from the metabolic activity of iron-oxidizing bacteria from the class
      Zetaproteobacteria, presumably enhanced by burrowing animals in coastal
      sediments. Zetaproteobacteria were estimated to be a global total of 1026 cells
      in coastal, bioturbated sediments, and predicted to annually produce 8 * 1015 g
      of Fe in sedimentary iron oxides-55 times larger than the annual flux of iron
      oxides deposited by rivers. These data suggest that iron-oxidizing
      Zetaproteobacteria are keystone organisms in marine sedimentary environments
      despite their low numerical abundance-yet exert a disproportionate impact via the
      rejuvenation of iron oxides.

PMID- 29343829
TI  - Targeted inhibitors of P-glycoprotein increase chemotherapeutic-induced mortality
      of multidrug resistant tumor cells.
AB  - Overexpression of ATP-binding cassette (ABC) transporters is often linked to
      multidrug resistance (MDR) in cancer chemotherapies. P-glycoprotein (P-gp) is one
      of the best studied drug transporters associated with MDR. There are currently no
      approved drugs available for clinical use in cancer chemotherapies to reverse MDR
      by inhibiting P-glycoprotein. Using computational studies, we previously
      identified several compounds that inhibit P-gp by targeting its nucleotide
      binding domain and avoiding its drug binding domains. Several of these compounds
      showed successful MDR reversal when tested on a drug resistant prostate cancer
      cell line. Using conventional two-dimensional cell culture of MDR ovarian and
      prostate cancer cells and three dimensional prostate cancer microtumor spheroids,
      we demonstrated here that co-administration with chemotherapeutics significantly
      decreased cell viability and survival as well as cell motility. The P-gp
      inhibitors were not observed to be toxic on their own. The inhibitors increased
      cellular retention of chemotherapeutics and reporter compounds known to be
      transport substrates of P-gp. We also showed that these compounds are not
      transport substrates of P-gp and that two of the three inhibit P-gp, but not the
      closely related ABC transporter, ABCG2/BCRP. The results presented suggest that
      these P-gp inhibitors may be promising leads for future drug development.

PMID- 29343831
TI  - Novel hydrogenases from deep-sea hydrothermal vent metagenomes identified by a
      recently developed activity-based screen.
AB  - Hydrogen is one of the most common elements on Earth. The enzymes converting
      molecular hydrogen into protons and electrons are the hydrogenases. Hydrogenases
      are ubiquitously distributed in all three domains of life where they play a
      central role in cell metabolism. So far, the recovery of hydrogenases has been
      restricted to culture-dependent and sequence-based approaches. We have recently
      developed the only activity-based screen for seeking H2-uptake enzymes from
      metagenomes without having to rely on enrichment and isolation of hydrogen
      oxidizing microorganisms or prior metagenomic sequencing. When screening 14,400
      fosmid clones from three hydrothermal vent metagenomes using this solely activity
      based approach, four clones with H2-uptake activity were identified with specific
      activities of up to 258 +/- 19 nmol H2/min/mg protein of partially purified
      membrane fractions. The respective metagenomic fragments exhibited mostly very
      low or no similarities to sequences in the public databases. A search with hidden
      Markov models for different hydrogenase groups showed no hits for three of the
      four metagenomic inserts, indicating that they do not encode for classical
      hydrogenases. Our activity-based screen serves as a powerful tool for the
      discovery of (novel) hydrogenases which would not have been identified by the
      currently available techniques. This screen can be ideally combined with culture-
      and sequence-based approaches to investigate the tremendous hydrogen-converting
      potential in the environment.

PMID- 29343832
TI  - Infection dynamics of insecticide-degrading symbionts from soil to insects in
      response to insecticide spraying.
AB  - Insecticide resistance is a serious concern in modern agriculture, and an
      understanding of the underlying evolutionary processes is pivotal to prevent the
      problem. The bean bug Riptortus pedestris, a notorious pest of leguminous crops,
      acquires a specific Burkholderia symbiont from the environment every generation,
      and harbors the symbiont in the midgut crypts. The symbiont's natural role is to
      promote insect development but the insect host can also obtain resistance against
      the insecticide fenitrothion (MEP) by acquiring MEP-degrading Burkholderia from
      the environment. To understand the developing process of the symbiont-mediated
      MEP resistance in response to the application of the insecticide, we investigated
      here in parallel the soil bacterial dynamics and the infected gut symbionts under
      different MEP-spraying conditions by culture-dependent and culture-independent
      analyses, in conjunction with stinkbug rearing experiments. We demonstrate that
      MEP application did not affect the total bacterial soil population but
      significantly decreased its diversity while it dramatically increased the
      proportion of MEP-degrading bacteria, mostly Burkholderia. Moreover, we found
      that the infection of stinkbug hosts with MEP-degrading Burkholderia is highly
      specific and efficient, and is established after only a few times of insecticide
      spraying at least in a field soil with spraying history, suggesting that
      insecticide resistance could evolve in a pest bug population more quickly than
      was thought before.

PMID- 29343834
TI  - Newly discovered Late Triassic Baqing eclogite in central Tibet indicates an
      anticlockwise West-East Qiangtang collision.
AB  - The Triassic eclogite-bearing central Qiangtang metamorphic belt (CQMB) in the
      northern Tibetan Plateau has been debated whether it is a metamorphic core
      complex underthrust from the Jinsha Paleo-Tethys or an in-situ Shuanghu suture.
      The CQMB is thus a key issue to elucidate the crustal architecture of the
      northern Tibetan Plateau, the tectonics of the eastern Tethys, and the
      petrogenesis of Cenozoic high-K magmatism. We here report the newly discovered
      Baqing eclogite along the eastern extension of the CQMB near the Baqing town,
      central Tibet. These eclogites are characterized by the garnet + omphacite +
      rutile + phengite + quartz assemblages. Primary eclogite-facies metamorphic
      pressure-temperature estimates yield consistent minimum pressure of 25 +/- 1 kbar
      at 730 +/- 60  degrees C. U-Pb dating on zircons that contain inclusions (garnet
      + omphacite + rutile + phengite) gave eclogite-facies metamorphic ages of 223 Ma.
      The geochemical continental crustal signature and the presence of Paleozoic cores
      in the zircons indicate that the Baqing eclogite formed by continental subduction
      and marks an eastward-younging anticlockwise West-East Qiangtang collision along
      the Shuanghu suture from the Middle to Late Triassic.

PMID- 29343833
TI  - Dopamine D3 receptor antagonist reveals a cryptic pocket in aminergic GPCRs.
AB  - The recent increase in the number of X-ray crystal structures of G-protein
      coupled receptors (GPCRs) has been enabling for structure-based drug design
      (SBDD) efforts. These structures have revealed that GPCRs are highly dynamic
      macromolecules whose function is dependent on their intrinsic flexibility.
      Unfortunately, the use of static structures to understand ligand binding can
      potentially be misleading, especially in systems with an inherently high degree
      of conformational flexibility. Here, we show that docking a set of dopamine D3
      receptor compounds into the existing eticlopride-bound dopamine D3 receptor (D3R)
      X-ray crystal structure resulted in poses that were not consistent with results
      obtained from site-directed mutagenesis experiments. We overcame the limitations
      of static docking by using large-scale high-throughput molecular dynamics (MD)
      simulations and Markov state models (MSMs) to determine an alternative pose
      consistent with the mutation data. The new pose maintains critical interactions
      observed in the D3R/eticlopride X-ray crystal structure and suggests that a
      cryptic pocket forms due to the shift of a highly conserved residue, F6.52. Our
      study highlights the importance of GPCR dynamics to understand ligand binding and
      provides new opportunities for drug discovery.

PMID- 29343835
TI  - A non-zircon Hf isotope record in Archean black shales from the Pilbara craton
      confirms changing crustal dynamics ca. 3 Ga ago.
AB  - Plate tectonics and associated subduction are unique to the Earth. Studies of
      Archean rocks show significant changes in composition and structural style around
      3.0 to 2.5 Ga that are related to changing tectonic regime, possibly associated
      with the onset of subduction. Whole rock Hf isotope systematics of black shales
      from the Australian Pilbara craton, selected to exclude detrital zircon
      components, are employed to evaluate the evolution of the Archean crust. This
      approach avoids limitations of Hf-in-zircon analyses, which only provide input
      from rocks of sufficient Zr-concentration, and therefore usually represent
      domains that already underwent a degree of differentiation. In this study, we
      demonstrate the applicability of this method through analysis of shales that
      range in age from 3.5 to 2.8 Ga, and serve as representatives of their crustal
      sources through time. Their Hf isotopic compositions show a trend from strongly
      positive epsilonHfinitial values for the oldest samples, to strongly negative
      values for the younger samples, indicating a shift from juvenile to
      differentiated material. These results confirm a significant change in the
      character of the source region of the black shales by 3 Ga, consistent with
      models invoking a change in global dynamics from crustal growth towards crustal
      reworking around this time.

PMID- 29343836
TI  - BPX-501 T cells interfere with minimal residual disease evaluation of B-cell
      acute lymphoblastic leukemia.

PMID- 29343838
TI  - Estimating the impact of body mass index on bladder cancer risk: Stratification
      by smoking status.
AB  - We estimated the impact of obesity on bladder cancer with stratification by
      smoking status using nationally representative data on the Korean population from
      the National Health Insurance System (NHIS). Of the 45,850,458 people who
      underwent at last one health examination from 2009 to 2012, 23,378,895 without
      bladder cancer were followed from the January 2009 to the December 2015. First,
      the HR for bladder cancer was lowest in people with a BMI < 18.5 (HR = 0.92) and
      highest for those with BMI >= 30 (HR = 1.17) in multiple Cox regression analyses.
      The positive association between bladder cancer and BMI showed an increasing
      trend beyond the reference BMI. Second, an analysis of HR for bladder cancer
      stratified by obesity across smoking status strata showed a significant trend of
      increasing HR for bladder cancer across obesity and smoking status in
      multivariate-adjusted models. Conclusively, this population-based study showed
      that increasing BMI was a risk factor for bladder cancer independent of
      confounding variables. When stratified by smoking status, there was still a
      positive association between bladder cancer and BMI (P for trend < 0.01).

PMID- 29343839
TI  - Musical auditory stimulus acutely influences heart rate dynamic responses to
      medication in subjects with well-controlled hypertension.
AB  - Music can improve the efficiency of medical treatment when correctly associated
      with drug action, reducing risk factors involving deteriorating cardiac function.
      We evaluated the effect of musical auditory stimulus associated with anti
      hypertensive medication on heart rate (HR) autonomic control in hypertensive
      subjects. We evaluated 37 well-controlled hypertensive patients designated for
      anti-hypertensive medication. Heart rate variability (HRV) was calculated from
      the HR monitor recordings of two different, randomly sorted protocols (control
      and music) on two separate days. Patients were examined in a resting condition 10
      minutes before medication and 20 minutes, 40 minutes and 60 minutes after oral
      medication. Music was played throughout the 60 minutes after medication with the
      same intensity for all subjects in the music protocol. We noted analogous
      response of systolic and diastolic arterial pressure in both protocols. HR
      decreased 60 minutes after medication in the music protocol while it remained
      unchanged in the control protocol. The effects of anti-hypertensive medication on
      SDNN (Standard deviation of all normal RR intervals), LF (low frequency, nu), HF
      (high frequency, nu) and alpha-1 scale were more intense in the music protocol.
      In conclusion, musical auditory stimulus increased HR autonomic responses to anti
      hypertensive medication in well-controlled hypertensive subjects.

PMID- 29343840
TI  - Vision Status in Older Adults: The Brazilian Amazon Region Eye Survey.
AB  - Older adults living in remote areas with limited access to health services are at
      higher risk to develop visual impairment and blindness. We conducted a population
      based survey to determine the vision status in subjects 45 years of age and older
      from urban and rural areas of Parintins city, Brazilian Amazon Region.
      Participants underwent ophthalmic examination, including uncorrected (UCVA),
      presenting (PVA) and best-corrected visual acuity (BCVA). Vision status was
      described as lines of visual acuity (VA) impairment and lines of VA improvement
      from UCVA to BCVA and from PVA to BCVA in the better-seeing eye. A total of 2384
      subjects were enumerated, 2041 (85.6%) were examined, with reliable VA
      measurements obtained from 2025 participants. Vision status in lines of VA
      impairment was (mean +/- standard deviation): 3.44 +/- 3.53 for UCVA, 2.85 +/-
      3.52 for PVA and 1.50 +/- 3.51 for BCVA. Female gender, older age and lower
      education were associated with >=6 lines of UCVA impairment. Lines of improvement
      >=3 was found in 626 (30.9%) participants and associated with female gender and
      rural residency. In conclusion, a third of participants could have at least three
      lines of VA improvement with proper refraction. Strategies to improve access to
      eye care and affordable glasses are needed.

PMID- 29343837
TI  - Neurocognitive dysfunction in hematopoietic cell transplant recipients: expert
      review from the late effects and Quality of Life Working Committee of the CIBMTR
      and complications and Quality of Life Working Party of the EBMT.
AB  - Hematopoietic cell transplantation (HCT) is a potentially curative treatment for
      children and adults with malignant and non-malignant diseases. Despite increasing
      survival rates, long-term morbidity following HCT is substantial. Neurocognitive
      dysfunction is a serious cause of morbidity, yet little is known about
      neurocognitive dysfunction following HCT. To address this gap, collaborative
      efforts of the Center for International Blood and Marrow Transplant Research and
      the European Society for Blood and Marrow Transplantation undertook an expert
      review of neurocognitive dysfunction following HCT. In this review, we define
      what constitutes neurocognitive dysfunction, characterize its risk factors and
      sequelae, describe tools and methods to assess neurocognitive function in HCT
      recipients, and discuss possible interventions for HCT patients with this
      condition. This review aims to help clinicians understand the scope of this
      health-related problem, highlight its impact on well-being of survivors, and to
      help determine factors that may improve identification of patients at risk for
      declines in cognitive functioning after HCT. In particular, we review strategies
      for preventing and treating neurocognitive dysfunction in HCT patients. Lastly,
      we highlight the need for well-designed studies to develop and test interventions
      aimed at preventing and improving neurocognitive dysfunction and its sequelae
      following HCT.

PMID- 29343841
TI  - Microdosimetric Modeling of Biological Effectiveness for Boron Neutron Capture
      Therapy Considering Intra- and Intercellular Heterogeneity in 10B Distribution.
AB  - We here propose a new model for estimating the biological effectiveness for boron
      neutron capture therapy (BNCT) considering intra- and intercellular heterogeneity
      in 10B distribution. The new model was developed from our previously established
      stochastic microdosimetric kinetic model that determines the surviving fraction
      of cells irradiated with any radiations. In the model, the probability density of
      the absorbed doses in microscopic scales is the fundamental physical index for
      characterizing the radiation fields. A new computational method was established
      to determine the probability density for application to BNCT using the Particle
      and Heavy Ion Transport code System PHITS. The parameters used in the model were
      determined from the measured surviving fraction of tumor cells administrated with
      two kinds of 10B compounds. The model quantitatively highlighted the
      indispensable need to consider the synergetic effect and the dose dependence of
      the biological effectiveness in the estimate of the therapeutic effect of BNCT.
      The model can predict the biological effectiveness of newly developed 10B
      compounds based on their intra- and intercellular distributions, and thus, it can
      play important roles not only in treatment planning but also in drug discovery
      research for future BNCT.

PMID- 29343843
TI  - Cathelicidin-OA1, a novel antioxidant peptide identified from an amphibian,
      accelerates skin wound healing.
AB  - Cathelicidins play pivotal roles in host defense. The discovery of novel
      cathelicidins is important research; however, despite the identification of many
      cathelicidins in vertebrates, few have been reported in amphibians. Here we
      identified a novel cathelicidin (named cathelicidin-OA1) from the skin of an
      amphibian species, Odorrana andersonii. Produced by posttranslational processing
      of a 198-residue prepropeptide, cathelicidin-OA1 presented an amino acid sequence
      of 'IGRDPTWSHLAASCLKCIFDDLPKTHN' and a molecular mass of 3038.5 Da. Functional
      analysis showed that, unlike other cathelicidins, cathelicidin-OA1 demonstrated
      no direct microbe-killing, acute toxicity and hemolytic activity, but did exhibit
      antioxidant activity. Importantly, cathelicidin-OA1 accelerated wound healing
      against human keratinocytes (HaCaT) and skin fibroblasts (HSF) in both time- and
      dose-dependent manners. Notably, cathelicidin-OA1 also showed wound-healing
      promotion in a mouse model with full-thickness skin wounds, accelerating re
      epithelialization and granulation tissue formation by enhancing the recruitment
      of macrophages to the wound site, inducing HaCaT cell proliferation and HSF cell
      migration. This is the first cathelicidin identified from an amphibian that shows
      potent wound-healing activity. These results will help in the development of new
      types of wound-healing agents and in our understanding of the biological
      functions of cathelicidins.

PMID- 29343844
TI  - Determinants of population responses to environmental fluctuations.
AB  - Environmental fluctuations, such as changing conditions and variable nutrient
      availability, are an unavoidable component of the dynamics of virtually all
      populations. They affect populations in ways that are often difficult to predict
      and sometimes lead to paradoxical outcomes. Here, we present a general analytical
      approach to examine how populations respond to fluctuations. We show that there
      exist general explicit conditions that determine to what extent fluctuations
      propagate to the variability of the responses and how they change the behavior of
      the system, including whether they promote proliferation or death and whether
      they facilitate coexistence or exclusion of competing species. These conditions
      depend on linear and nonlinear terms of the growth rate and on the characteristic
      times of the fluctuations. We validated our general approach through
      computational experiments for both stochastic and chaotic fluctuations and for
      multiple types of systems. From an applied point of view, our results provide an
      avenue for the precise control of the population behavior through fluctuations in
      addition to just through average properties.

PMID- 29343842
TI  - Leptin resistance was involved in susceptibility to overweight in the striped
      hamster re-fed with high fat diet.
AB  - Food restriction (FR) is the most commonly used intervention to prevent the
      overweight. However, the lost weight is usually followed by "compensatory growth"
      when FR ends, resulting in overweight. The present study was aimed to examining
      the behavior patterns and hormones mechanisms underpinning the over-weight.
      Energy budget and body fat content, and several endocrine markers related to
      leptin signals were examined in the striped hamsters under 20% FR refed by either
      low-fat diet (LF group) or high-fat diet (HF group). Body mass and fat content
      significantly regained when FR ended, and the hamsters in HF group showed 49.1%
      more body fat than in LF group (P < 0.01). Digestive energy intake was higher by
      20.1% in HF than LF group, while metabolic thermogenesis and behavior patterns
      did not differed between the two groups. Gene expression of leptin receptor and
      anorexigenic peptides of pro-opiomelanocortin and cocaine- and amphetamine
      regulated transcript in hypothalamus were significantly up-regulated in LF group,
      but down-regulated in HF group. It suggests that effective leptin signals to the
      brain were involved in attenuation of hyperphagia in hamsters refed with LF.
      However, "leptin resistance" probably occurred in hamsters refed with HF, which
      impaired the control of hyperphagia, resulting in development of over-weight.

PMID- 29343845
TI  - Metal-free magnetism, spin-dependent Seebeck effect, and spin-Seebeck diode
      effect in armchair graphene nanoribbons.
AB  - Metal-free magnetism and spin caloritronics are at the forefront of condensed
      matter physics. Here, the electronic structures and thermal spin-dependent
      transport properties of armchair graphene nanoribbons (N-AGNRs), where N is the
      ribbon width (N = 5-23), are systematically studied. The results show that the
      indirect band gaps exhibit not only oscillatory behavior but also periodic
      characteristics with E 3p  > E3p+1 > E3p+2 (E 3p , E3p+1 and E3p+2 are the band
      gaps energy) for a certain integer p, with increasing AGNR width. The magnetic
      ground states are ferromagnetic (FM) with a Curie temperatures (T C ) above room
      temperature. Furthermore, the spin-up and spin-down currents with opposite
      directions, generated by a temperature gradient, are almost symmetrical,
      indicating the appearance of the perfect spin-dependent Seebeck effect (SDSE).
      Moreover, thermally driven spin currents through the nanodevices induced the spin
      Seebeck diode (SSD) effect. Our calculation results indicated that AGNRs can be
      applied in thermal spin nanodevices.

PMID- 29343846
TI  - Author Correction: CODA: Integrating multi-level context-oriented directed
      associations for analysis of drug effects.
AB  - A correction to this article has been published and is linked from the HTML
      version of this paper. The error has been fixed in the paper.

PMID- 29343847
TI  - Neural substrates of purely endogenous, self-regulatory control of attention.
AB  - Stimulus-driven orienting of attention toward a novel, salient stimulus is a
      highly adaptive behavior. In an opposing vein, it is also crucial to endogenously
      redirect attention to other stimuli of behavioral significance if the attended
      stimulus was evaluated to be unimportant. This stimulus-driven orienting and
      subsequent reorienting of attention are known to be mediated by similar neural
      substrates. However, this might be because reorienting was triggered by a sensory
      transition exogenously capturing attention, such as an abrupt onset of a new
      stimulus. Here, we used fMRI to measure the human brain's activity when attention
      captured by a salient distractor is endogenously reoriented toward the concurrent
      main task, without any exogenous shifting of attention. As results, the transient
      activity of the anterior insula (AI) signaled such endogenous reorienting,
      predicting behavioral performance. This finding points to the central role of the
      AI in purely endogenous, self-regulatory control of attention.

PMID- 29343848
TI  - A novel protein encoded by the circular form of the SHPRH gene suppresses glioma
      tumorigenesis.
AB  - Circular RNAs (circRNAs) are recognized as functional non-coding transcripts in
      eukaryotic cells. Recent evidence has indicated that even though circRNAs are
      generally expressed at low levels, they may be involved in many physiological or
      pathological processes, such as gene regulation, tissue development and
      carcinogenesis. Although the 'microRNA sponge' function is well characterized,
      most circRNAs do not contain perfect trapping sites for microRNAs, which suggests
      the possibility that circRNAs have functions that have not yet been defined. In
      this study, we show that a circRNA containing an open reading frame (ORF) driven
      by the internal ribosome entry site (IRES) can translate a functional protein.
      The circular form of the SNF2 histone linker PHD RING helicase (SHPRH) gene
      encodes a novel protein that we termed SHPRH-146aa. Circular SHPRH (circ-SHPRH)
      uses overlapping genetic codes to generate a 'UGA' stop codon, which results in
      the translation of the 17 kDa SHPRH-146aa. Both circ-SHPRH and SHPRH-146aa are
      abundantly expressed in normal human brains and are down-regulated in
      glioblastoma. The overexpression of SHPRH-146aa in U251 and U373 glioblastoma
      cells reduces their malignant behavior and tumorigenicity in vitro and in vivo.
      Mechanistically, SHPRH-146aa protects full-length SHPRH from degradation by the
      ubiquitin proteasome. Stabilized SHPRH sequentially ubiquitinates proliferating
      cell nuclear antigen (PCNA) as an E3 ligase, leading to inhibited cell
      proliferation and tumorigenicity. Our findings provide a novel perspective
      regarding circRNA function in physiological and pathological processes.
      Specifically, SHPRH-146aa generated from overlapping genetic codes of circ-SHPRH
      is a tumor suppressor in human glioblastoma.

PMID- 29343849
TI  - Mutant p53 gain of function underlies high expression levels of colorectal cancer
      stem cells markers.
AB  - Emerging notion in carcinogenesis ascribes tumor initiation and aggressiveness to
      cancer stem cells (CSCs). Specifically, colorectal cancer (CRC) development was
      shown to be compatible with CSCs hypothesis. Mutations in p53 are highly frequent
      in CRC, and are known to facilitate tumor development and aggressiveness. Yet,
      the link between mutant p53 and colorectal CSCs is not well-established. In the
      present study, we set to examine whether oncogenic mutant p53 proteins may
      augment colorectal CSCs phenotype. By genetic manipulation of mutant p53 in
      several cellular systems, we demonstrated that mutant p53 enhances colorectal
      tumorigenesis. Moreover, mutant p53-expressing cell lines harbor larger sub
      populations of cells highly expressing the known colorectal CSCs markers: CD44,
      Lgr5, and ALDH. This elevated expression is mediated by mutant p53 binding to
      CD44, Lgr5, and ALDH1A1 promoter sequences. Furthermore, ALDH1 was found to be
      involved in mutant p53-dependent chemotherapy resistance. Finally, analysis of
      ALDH1 and CD44 in human CRC biopsies indicated a positive correlation between
      their expression and the presence of oncogenic p53 missense mutations. These
      findings suggest novel insights pertaining the mechanism by which mutant p53
      enhances CRC development, which involves the expansion of CSCs sub-populations
      within CRC tumors, and underscore the importance of targeting these sub
      populations for CRC therapy.

PMID- 29343850
TI  - MiRNA-646-mediated reciprocal repression between HIF-1alpha and MIIP contributes
      to tumorigenesis of pancreatic cancer.
AB  - Migration and invasion inhibitory protein (MIIP) is recently identified as an
      inhibitor in tumor development. However, the regulatory mechanism and biological
      contributions of MIIP in pancreatic cancer (PC) have been not elucidated. In this
      study, we demonstrated a negative feedback of MIIP and hypoxia-induced factor
      1alpha (HIF-1alpha), which was mediated by a hypoxia-induced microRNA. Compared
      with paracarcinoma tissues, MIIP was downregulated in PC tissues. Overexpression
      of MIIP significantly impeded the proliferation and invasion of PC cells both in
      vitro and in mouse xenograft models. We further verified MIIP was downregulated
      under hypoxia in a HIF-1alpha-mediated manner. Interestingly, although MIIP
      promoter containing two putative hypoxia response elements (HREs), the chromatin
      immunoprecipitation (ChIP) and luciferase reporter assays did not support an
      active interaction between HIF-1alpha and MIIP promoter. Meanwhile, microRNA
      array revealed a hypoxia-induced microRNA, miR-646, impaired stability of MIIP
      mRNA and consequently inhibited its expression by targeting the coding sequence
      (CDS). Coincidently, knockdown of miR-646 significantly repressed proliferation
      and invasion ability of PC cells both in vitro and in vivo by upregulating MIIP
      expression. Besides, ChIP and luciferase reporter assays further validated that
      HIF-1alpha activated transcription of miR-646 in hypoxia condition. Therefore,
      these results suggested HIF-1alpha indirectly regulated MIIP expression in post
      transcriptional level through upregulating miR-646 transcription. Conversely, our
      results further revealed that MIIP suppressed deacetylase ability of histone
      deacetylase 6 (HDAC6) to promote the acetylation and degradation of HIF-1alpha,
      by which impairing HIF-1alpha accumulation. What is more, a specific relationship
      between downregulated MIIP and upregulated miR-646 expression was validated in PC
      samples. Moreover, the dysregulated miR-646 and MIIP expression was correlated
      with advanced tumor stage, lymphatic invasion, metastasis and shorter overall
      survival in PC patients. Together, our results highlight that the reciprocal loop
      of HIF-1alpha/miR-646/MIIP might be implemented as an applicable target for
      pancreatic cancer therapy.

PMID- 29343851
TI  - NDRG2 facilitates colorectal cancer differentiation through the regulation of
      Skp2-p21/p27 axis.
AB  - Poorly differentiated colorectal cancers (CRCs) are more aggressive and lack
      targeted therapies. We and others previously reported the predominant role of
      tumor-suppressor NDRG2 in promoting CRC differentiation, but the underlying
      mechanism is largely unknown. Herein, we demonstrate that NDRG2 induction of CRC
      cell differentiation is dependent on the repression of E3 ligase Skp2 activity.
      In patients and Ndrg2 knockout mice, NDRG2 and Skp2 are negatively correlated and
      associated with cell differentiation stage. Further, NDRG2 suppression of Skp2
      contributes to the inductions and stabilizations of p21 and p27, which are Skp2
      target proteins for degradation. The reduction of either p21 or p27 levels by
      shRNA can decrease NDRG2-induced AKP activity and resume cell growth inhibition,
      thus both p21 and p27 are required for NDRG2 effect on the promotion of cell
      differentiation in CRCs. The mechanistic study shows that NDRG2 suppresses beta
      catenin nuclear translocation and decreases the occupancy of beta-catenin/TCF
      complex on Skp2 promoter, potentially through dephosphorylating GSK-3beta. By
      subjecting a series of NDRG2 deletion mutants to Skp2 expression, the loss of NH2
      terminal domain can completely abolish NDRG2-dependent differentiation induction.
      Supporting the biological significance of the reciprocal relationship between
      NDRG2 and Skp2, an NDRG2low/Skp2high gene expression signature correlates with
      poor CRC patient outcome and could be considered as a diagnostic marker of CRCs.

PMID- 29343852
TI  - A new class of magnetically actuated pumps and valves for microfluidic
      applications.
AB  - We propose a new class of magnetically actuated pumps and valves that could be
      incorporated into microfluidic chips with no further external connections. The
      idea is to repurpose ferromagnetic low Reynolds number swimmers as devices
      capable of generating fluid flow, by restricting the swimmers' translational
      degrees of freedom. We experimentally investigate the flow structure generated by
      a pinned swimmer in different scenarios, such as unrestricted flow around it as
      well as flow generated in straight, cross-shaped, Y-shaped and circular channels.
      This demonstrates the feasibility of incorporating the device into a channel and
      its capability of acting as a pump, valve and flow splitter. Different regimes
      could be selected by tuning the frequency and amplitude of the external magnetic
      field driving the swimmer, or by changing the channel orientation with respect to
      the field. This versatility endows the device with varied functionality which,
      together with the robust remote control and reproducibility, makes it a promising
      candidate for several applications.

PMID- 29343854
TI  - Towards healthier supermarkets: a national study of in-store food availability,
      prominence and promotions in New Zealand.
AB  - BACKGROUND/OBJECTIVES: The retail environment is a key setting for potential
      public health interventions. This study assessed the healthiness of New Zealand
      supermarket food environments. SUBJECT/METHODS: A sample of 204 (about 50% of
      national total) supermarkets across three chains was selected in 2016, half in
      the most deprived socioeconomic areas. Healthiness indicators related to food
      availability (ratio of cumulative linear shelf length for healthy versus
      unhealthy foods), prominence (proportion of 'junk food free' check-outs and end
      of-aisle endcaps), and promotion (proportion of 'junk food free' promotions in
      flyers and in-store) were measured. RESULTS: About 26.5% of supermarkets had at
      least 20% of check-outs junk-food-free and 17.2% had at least 60% of endcaps junk
      food free. On average 2/3 of food promotions in-store and 3/4 of food promotions
      in flyers were junk food free. For every 1 m of shelf length for unhealthy foods,
      there was 42 cm of shelf length for healthy foods on average, with large
      variations between and within stores. In high and low prominence store areas
      there was on average 1 m of unhealthy foods for every 2 cm of healthy foods and 1
      m of unhealthy foods for every 4 m of healthy foods, respectively. The shelf
      length ratio was significantly lower in the most compared to the least/medium
      deprived socioeconomic areas (p = 0.003). CONCLUSIONS: The large variations in
      healthiness indicators within and across chains present a great opportunity for
      retailers to improve the healthiness of supermarkets towards best practice.

PMID- 29343853
TI  - Differential tissue specific, temporal and spatial expression patterns of the
      Aggrecan gene is modulated by independent enhancer elements.
AB  - The transcriptional mechanism through which chondrocytes control the spatial and
      temporal composition of the cartilage tissue has remained largely elusive. The
      central aim of this study was to identify whether transcriptional enhancers
      played a role in the organisation of the chondrocytes in cartilaginous tissue. We
      focused on the Aggrecan gene (Acan) as it is essential for the normal structure
      and function of cartilage and it is expressed developmentally in different stages
      of chondrocyte maturation. Using transgenic reporter studies in mice we
      identified four elements, two of which showed individual chondrocyte
      developmental stage specificity. In particular, one enhancer (-80) distinguishes
      itself from the others by being predominantly active in adult cartilage.
      Furthermore, the -62 element uniquely drove reporter activity in early
      chondrocytes. The remaining chondrocyte specific enhancers, +28 and -30, showed
      no preference to chondrocyte type. The transcription factor SOX9 interacted with
      all the enhancers in vitro and mutation of SOX9 binding sites in one of the
      enhancers (-30) resulted in a loss of its chondrocyte specificity and ectopic
      enhancer reporter activity. Thus, the Acan enhancers orchestrate the precise
      spatiotemporal expression of this gene in cartilage types at different stages of
      development and adulthood.

PMID- 29343855
TI  - The ferroptosis inducer erastin irreversibly inhibits system xc- and synergizes
      with cisplatin to increase cisplatin's cytotoxicity in cancer cells.
AB  - System xc- was recently described as the most upstream node in a novel form of
      regulated necrotic cell death, called ferroptosis. In this context, the small
      molecule erastin was reported to target and inhibit system xc-, leading to
      cysteine starvation, glutathione depletion and consequently ferroptotic cell
      death. Although the inhibitory effect of erastin towards system xc- is well
      documented, nothing is known about its mechanism of action. Therefore, we sought
      to interrogate in more detail the underlying mechanism of erastin's pro
      ferroptotic effects. When comparing with some well-known inhibitors of system xc
      , erastin was the most efficient inhibitor acting at low micromolar
      concentrations. Notably, only a very short exposure of cells with low erastin
      concentrations was sufficient to cause a strong and persistent inhibition of
      system xc-, causing glutathione depletion. These inhibitory effects towards
      system xc- did not involve cysteine modifications of the transporter. More
      importantly, short exposure of tumor cells with erastin strongly potentiated the
      cytotoxic effects of cisplatin to efficiently eradicate tumor cells. Hence, our
      data suggests that only a very short pre-treatment of erastin suffices to
      synergize with cisplatin to efficiently induce cancer cell death, findings that
      might guide us in the design of novel cancer treatment paradigms.

PMID- 29343856
TI  - Deep-Ultraviolet AlGaN/AlN Core-Shell Multiple Quantum Wells on AlN Nanorods via
      Lithography-Free Method.
AB  - We report deep ultraviolet (UVC) emitting core-shell-type AlGaN/AlN multiple
      quantum wells (MQWs) on the AlN nanorods which are prepared by
      catalyst/lithography free process. The MQWs are grown on AlN nanorods on a
      sapphire substrate by polarity-selective epitaxy and etching (PSEE) using high
      temperature metal organic chemical vapor deposition. The AlN nanorods prepared
      through PSEE have a low dislocation density because edge dislocations are bent
      toward neighboring N-polar AlN domains. The core-shell-type MQWs grown on AlN
      nanorods have three crystallographic orientations, and the final shape of the
      grown structure is explained by a ball-and-stick model. The photoluminescence
      (PL) intensity of MQWs grown on AlN nanorods is approximately 40 times higher
      than that of MQWs simultaneously grown on a planar structure. This result can be
      explained by increased internal quantum efficiency, large active volume, and
      increase in light extraction efficiency based on the examination in this study.
      Among those effects, the increase of active volume on AlN nanorods is considered
      to be the main reason for the enhancement of the PL intensity.

PMID- 29343857
TI  - Stimulation of Epicardial Sympathetic Nerves at Different Sites Induces Cardiac
      Electrical Instability to Various Degrees.
AB  - The cardiac sympathetic nerves distribute across cardiac tissues with uneven
      density. Yet, to what extent this anatomical heterogeneity affects electrical
      activity of the left ventricle is largely unknown. Dogs were randomized into non
      stimulation control (NC), posterior basal-stimulation (PB), anterior superior
      stimulation (AS), apical part-stimulation (AP) group. The epicardial sympathetic
      nerves at different sites along their distribution were with electrical
      stimulation (ES) for 4 hours except in the NC group. The myocardial effective
      refractory period (ERP), ventricular fibrillation threshold (VFT) and density of
      sympathetic nerves were recorded. Compared with ES at other places, the
      stimulation at PB site significantly shortened ERP (left ventricular anterior and
      posterior walls; PB group, 118 +/- 4 ms, 106 +/- 2 ms; Versus NC group, 155 +/-
      3.5 ms, 160 +/- 3 ms; p < 0.01) and VFT (PB group, 11.5 +/- 1.5 V; Versus NC
      group, 20.5 +/- 0.9 V; p < 0.01), and induced remarkable regeneration of the
      cardiac sympathetic nerves, hence influencing electrical activity of the left
      ventricle to the most extent. Our study demonstrates that the degree of induced
      ventricular electrical instability is correlated tightly with the density of
      sympathetic nerves around ES site, and PB site is a potential target for
      modulating ventricular electrical activity to the maximal extent.

PMID- 29343859
TI  - Rate after-effects fail to transfer cross-modally: Evidence for distributed
      sensory timing mechanisms.
AB  - Accurate time perception is critical for a number of human behaviours, such as
      understanding speech and the appreciation of music. However, it remains
      unresolved whether sensory time perception is mediated by a central timing
      component regulating all senses, or by a set of distributed mechanisms, each
      dedicated to a single sensory modality and operating in a largely independent
      manner. To address this issue, we conducted a range of unimodal and cross-modal
      rate adaptation experiments, in order to establish the degree of specificity of
      classical after-effects of sensory adaptation. Adapting to a fast rate of sensory
      stimulation typically makes a moderate rate appear slower (repulsive after
      effect), and vice versa. A central timing hypothesis predicts general transfer of
      adaptation effects across modalities, whilst distributed mechanisms predict a
      high degree of sensory selectivity. Rate perception was quantified by a method of
      temporal reproduction across all combinations of visual, auditory and tactile
      senses. Robust repulsive after-effects were observed in all unimodal rate
      conditions, but were not observed for any cross-modal pairings. Our results show
      that sensory timing abilities are adaptable but, crucially, that this change is
      modality-specific - an outcome that is consistent with a distributed sensory
      timing hypothesis.

PMID- 29343858
TI  - Developmental pathways inferred from modularity, morphological integration and
      fluctuating asymmetry patterns in the human face.
AB  - Facial asymmetries are usually measured and interpreted as proxies to
      developmental noise. However, analyses focused on its developmental and genetic
      architecture are scarce. To advance on this topic, studies based on a
      comprehensive and simultaneous analysis of modularity, morphological integration
      and facial asymmetries including both phenotypic and genomic information are
      needed. Here we explore several modularity hypotheses on a sample of Latin
      American mestizos, in order to test if modularity and integration patterns differ
      across several genomic ancestry backgrounds. To do so, 4104 individuals were
      analyzed using 3D photogrammetry reconstructions and a set of 34 facial landmarks
      placed on each individual. We found a pattern of modularity and integration that
      is conserved across sub-samples differing in their genomic ancestry background.
      Specifically, a signal of modularity based on functional demands and organization
      of the face is regularly observed across the whole sample. Our results shed more
      light on previous evidence obtained from Genome Wide Association Studies
      performed on the same samples, indicating the action of different genomic regions
      contributing to the expression of the nose and mouth facial phenotypes. Our
      results also indicate that large samples including phenotypic and genomic
      metadata enable a better understanding of the developmental and genetic
      architecture of craniofacial phenotypes.

PMID- 29343860
TI  - Predicted impact of thermal power generation emission control measures in the
      Beijing-Tianjin-Hebei region on air pollution over Beijing, China.
AB  - Widespread economic growth in China has led to increasing episodes of severe air
      pollution, especially in major urban areas. Thermal power plants represent a
      particularly important class of emissions. Here we present an evaluation of the
      predicted effectiveness of a series of recently proposed thermal power plant
      emission controls in the Beijing-Tianjin-Hebei (BTH) region on air quality over
      Beijing using the Community Multiscale Air Quality(CMAQ) atmospheric chemical
      transport model to predict CO, SO2, NO2, PM2.5, and PM10 levels. A baseline
      simulation of the hypothetical removal of all thermal power plants in the BTH
      region is predicted to lead to 38%, 23%, 23%, 24%, and 24% reductions in current
      annual mean levels of CO, SO2, NO2, PM2.5, and PM10 in Beijing, respectively.
      Similar percentage reductions are predicted in the major cities in the BTH
      region. Simulations of the air quality impact of six proposed thermal power plant
      emission reduction strategies over the BTH region provide an estimate of the
      potential improvement in air quality in the Beijing metropolitan area, as a
      function of the time of year.

PMID- 29343861
TI  - Sensing Native Protein Solution Structures Using a Solid-state Nanopore:
      Unraveling the States of VEGF.
AB  - Monitoring individual proteins in solution while simultaneously obtaining
      tertiary and quaternary structural information is challenging. In this study,
      translocation of the vascular endothelial growth factor (VEGF) protein through a
      solid-state nanopore (ssNP) produces distinct ion-current blockade amplitude
      levels and durations likely corresponding to monomer, dimer, and higher
      oligomeric states. Upon changing from a non-reducing to a reducing condition, ion
      current blockage events from the monomeric state dominate, consistent with the
      expected reduction of the two inter-chain VEGF disulfide bonds. Cleavage by
      plasmin and application of either a positive or a negative NP bias results in
      nanopore signals corresponding either to the VEGF receptor recognition domain or
      to the heparin binding domain, accordingly. Interestingly, multi-level analysis
      of VEGF events reveals how individual domains affect their translocation pattern.
      Our study shows that careful characterization of ssNP results elucidates real
      time structural information about the protein, thereby complementing classical
      techniques for structural analysis of proteins in solution with the added
      advantage of quantitative single-molecule resolution of native proteins.

PMID- 29343862
TI  - Angiotensin II Overstimulation Leads to an Increased Susceptibility to Dilated
      Cardiomyopathy and Higher Mortality in Female Mice.
AB  - Heart failure (HF) is associated with high mortality and affects men and women
      differently. The underlying mechanisms for these sex-related differences remain
      largely unexplored. Accordingly, using mice with cardiac-specific overexpression
      of the angiotensin II (ANGII) type 1 receptor (AT1R), we explored male-female
      differences in the manifestations of hypertrophy and HF. AT1R mice of both sexes
      feature electrical and Ca2+ handling alterations, systolic dysfunction,
      hypertrophy and develop HF. However, females had much higher mortality (21.0%)
      rate than males (5.5%). In females, AT1R stimulation leads to more pronounced
      eccentric hypertrophy (larger increase in LV mass/body weight ratio [+31%], in
      cell length [+27%], in LV internal end-diastolic [LVIDd, +34%] and systolic
      [LVIDs, +67%] diameter) and dilation (larger decrease in LV posterior wall
      thickness, +17%) than males. In addition, in female AT1R mice the cytosolic Ca2+
      extrusion mechanisms were more severely compromised and were associated with a
      specific increased in Ca2+ sparks (by 187%) and evidence of SR Ca2+ leak.
      Altogether, these results suggest that female AT1R mice have more severe
      eccentric hypertrophy, dysfunction and compromised Ca2+ dynamics. These findings
      indicate that females are more susceptible to the adverse effects of AT1R
      stimulation than males favouring the development of HF and increased mortality.

PMID- 29343863
TI  - Genetic analyses favour an ancient and natural origin of elephants on Borneo.
AB  - The origin of the elephant on the island of Borneo remains elusive. Research has
      suggested two alternative hypotheses: the Bornean elephant stems either from a
      recent introduction in the 17th century or from an ancient colonization several
      hundreds of thousands years ago. Lack of elephant fossils has been interpreted as
      evidence for a very recent introduction, whereas mtDNA divergence from other
      Asian elephants has been argued to favor an ancient colonization. We investigated
      the demographic history of Bornean elephants using full-likelihood and
      approximate Bayesian computation analyses. Our results are at odds with both the
      recent and ancient colonization hypotheses, and favour a third intermediate
      scenario. We find that genetic data favour a scenario in which Bornean elephants
      experienced a bottleneck during the last glacial period, possibly as a
      consequence of the colonization of Borneo, and from which it has slowly recovered
      since. Altogether the data support a natural colonization of Bornean elephants at
      a time when large terrestrial mammals could colonise from the Sunda shelf when
      sea levels were much lower. Our results are important not only in understanding
      the unique history of the colonization of Borneo by elephants, but also for their
      long-term conservation.

PMID- 29343864
TI  - Electrochemical and Friction Characteristics of Metallic Glass Composites at the
      Microstructural Length-scales.
AB  - Metallic glass composites represent a unique alloy design strategy comprising of
      in situ crystalline dendrites in an amorphous matrix to achieve damage tolerance
      unseen in conventional structural materials. They are promising for a range of
      advanced applications including spacecraft gears, high-performance sporting goods
      and bio-implants, all of which demand high surface degradation resistance. Here,
      we evaluated the phase-specific electrochemical and friction characteristics of a
      Zr-based metallic glass composite, Zr56.2Ti13.8Nb5.0Cu6.9Ni5.6Be12.5, which
      comprised roughly of 40% by volume crystalline dendrites in an amorphous matrix.
      The amorphous matrix showed higher hardness and friction coefficient compared to
      the crystalline dendrites. But sliding reciprocating tests for the composite
      revealed inter-phase delamination rather than preferred wearing of one phase.
      Pitting during potentiodynamic polarization in NaCl solution was prevalent at the
      inter-phase boundary, confirming that galvanic coupling was the predominant
      corrosion mechanism. Scanning vibration electrode technique demonstrated that the
      amorphous matrix corroded much faster than the crystalline dendrites due to its
      unfavorable chemistry. Relative work function values measured using scanning
      kelvin probe showed the amorphous matrix to be more electropositive, which
      explain its preferred corrosion over the crystalline dendrites as well as its
      characteristic friction behavior. This study paves the way for careful
      partitioning of elements between the two phases in a metallic glass composite to
      tune its surface degradation behavior for a range of advanced applications.

PMID- 29343865
TI  - Targeting murine leukemic stem cells by antibody functionalized mesoporous silica
      nanoparticles.
AB  - Acute leukemia is initiated and maintained by leukemia stem cells (LSCs) and
      therefore there is great interest to develop innovative therapeutic approaches
      which target LSCs. Here we show that mesoporous silica nanoparticles (MSNs)
      functionalized with succinic anhydride, tagged with an anti-B220 antibody and
      loaded with the anthracycline daunorubicin are efficiently incorporated into
      murine B220-positive AML LSCs and preferentially kill these cells in comparison
      to B220-negative AML LSCs in vitro. Furthermore, short - term treatment of the
      AML LSCs with these MSNs before transplant significantly delayed leukemia
      development in recipient mice. These data demonstrate that targeting of AML LSCs
      can be improved by using functionalized and antigen directed MSNs as carriers for
      anti-leukemic drugs.

PMID- 29343866
TI  - Identification of JAZ-interacting MYC transcription factors involved in latex
      drainage in Hevea brasiliensis.
AB  - Hevea brasiliensis Mull. Arg. is one of the most frequently wounded plants
      worldwide. Expelling latex upon mechanical injury is a wound response of rubber
      trees. However, JA-mediated wound responses in rubber trees are not well
      documented. In this work, three JAZ-interacting MYC transcription factors of H.
      brasiliensis (termed HbMYC2/3/4) were identified by yeast two-hybrid screening.
      HbMYC2/3/4 each showed specific interaction profiles with HbJAZs. HbMYC2/3/4 each
      localized in the nucleus and exhibited strong transcriptional activity. To
      identify the target genes potentially regulated by HbMYC2/3/4, cis-elements
      interacting with HbMYC2/3/4 were first screened by yeast one-hybrid assays; the
      results indicated that HbMYC2/3/4 each could bind G-box elements. Additional
      analysis confirmed that HbMYC2/3/4 bound the HbPIP2;1 promoter, which contains
      five G-box cis-elements, and regulated the expression of reporter genes in yeast
      cells and in planta. HbMYC2/3/4 were induced by exogenous JA treatment but
      suppressed by ethylene (ET) treatment; in contrast, HbPIP2;1 was positively
      regulated by ET but negatively regulated by JA treatment. Given that HbPIP2;1 is
      involved in latex drainage, it could be proposed that HbMYC2/3/4 are involved in
      the regulation of HbPIP2;1 expression as well as latex drainage, both of which
      are coordinated by the JA and ET signalling pathways.

PMID- 29343867
TI  - Improving survival of acute-on-chronic liver failure patients complicated with
      invasive pulmonary aspergillosis.
AB  - The mortality of acute-on-chronic liver failure (ACLF) patients complicated with
      invasive pulmonary aspergillosis (IPA) was extremely high. We aimed to explore
      prognostic value of the Chronic Liver Failure-Sequential Organ Failure Assessment
      (CLIF-SOFA) lung score and to establish an optimal voriconazole regimen for ACLF
      patients complicated with IPA. We retrospectively screened hospitalized ACLF
      patients in our hospital from July 2011 to April 2016, from which 20 probable IPA
      cases were diagnosed. Along with onsets of IPA, deteriorated diseases severity,
      especially lung conditions were found in those 20 ACLF patients. It was found
      that IPA patients with CLIF-SOFA lung score <2 had better 28-day survival than
      those with lung score >1 (11/13 vs 0/7, p < 0.001). Based on plasma voriconazole
      concentration measurement, an optimal voriconazole regimen (loading doses: 0.2 g
      twice daily; maintenance doses, 0.1 g once daily) was established, which resulted
      in rational trough plasma drug concentrations (1-5 MUg/mL), good clinical
      outcomes (90-day survival rate of 6/8) and no observed adverse events. In
      conclusion, CLIF-SOFA lung score >1 was able to identify ACLF patients
      complicated with IPA encountering much higher 28-day mortality. An optimal
      voriconazole regimen was safe and effective in our ACLF patients complicated with
      IPA.

PMID- 29343868
TI  - Galectin-13, a different prototype galectin, does not bind beta-galacto-sides and
      forms dimers via intermolecular disulfide bridges between Cys-136 and Cys-138.
AB  - During pregnancy, placental protein-13 (galectin-13) is highly expressed in the
      placenta and fetal tissue, and less so in maternal serum that is related to pre
      eclampsia. To understand galectin-13 function at the molecular level, we solved
      its crystal structure and discovered that its dimer is stabilized by two
      disulfide bridges between Cys136 and Cys138 and six hydrogen bonds involving
      Val135, Val137, and Gln139. Native PAGE and gel filtration demonstrate that this
      is not a crystallization artifact because dimers also form in solution. Our
      biochemical studies indicate that galectin-13 ligand binding specificity is
      different from that of other galectins in that it does not bind beta
      galactosides. This is partly explained by the presence of Arg53 rather than His53
      at the bottom of the carbohydrate binding site in a position that is crucial for
      interactions with beta-galactosides. Mutating Arg53 to histidine does not re
      establish normal beta-galactoside binding, but rather traps cryoprotectant
      glycerol molecules within the ligand binding site in crystals of the R53H mutant.
      Moreover, unlike most other galectins, we also found that GFP-tagged galectin-13
      is localized within the nucleus of HeLa and 293 T cells. Overall, galectin-13
      appears to be a new type of prototype galectin with distinct properties.

PMID- 29343869
TI  - Spatiotemporal allele organization by allele-specific CRISPR live-cell imaging
      (SNP-CLING).
AB  - Imaging and chromatin capture techniques have provided important insights into
      our understanding of nuclear organization. A limitation of these techniques is
      the inability to resolve allele-specific spatiotemporal properties of genomic
      loci in living cells. Here, we describe an allele-specific CRISPR live-cell DNA
      imaging technique (SNP-CLING) to provide the first comprehensive insights into
      allelic positioning across space and time in mouse embryonic stem cells and
      fibroblasts. With 3D imaging, we studied alleles on different chromosomes in
      relation to one another and relative to nuclear substructures such as the
      nucleolus. We find that alleles maintain similar positions relative to each other
      and the nucleolus; however, loci occupy unique positions. To monitor
      spatiotemporal dynamics by SNP-CLING, we performed 4D imaging and determined that
      alleles are either stably positioned or fluctuating during cell state
      transitions, such as apoptosis. SNP-CLING is a universally applicable technique
      that enables the dissection of allele-specific spatiotemporal genome organization
      in live cells.

PMID- 29343870
TI  - Italian law n. 24/2017 on physicians' criminal liability: a reform that does not
      solve the problems of the psychiatric practice
AB  - For years psychiatrists have been facing the risk of being prosecuted for
      professional liability. One of the reasons for this situation depends on the fact
      that professionals cannot rely on clear rules of conduct. Indeed, in psychiatry,
      it may happen that a judge considers negligent a conduct not punishable by
      another court, as in cases of hospital discharges. In order to solve this
      situation, on March 8, 2017 Italian legislators issued the law no. 24. First of
      all, it establishes that health care providers must follow the guidelines that
      will be published on the website of the High Institute of Health, with the
      exception of specific situations on a given case. In the absence of such
      guidelines, the good clinical-care practice should be applied (Art. 5). In
      addition, if health care providers have met the guidelines as appropriate to the
      specific case or, in their absence, to the good clinical-care practice, they
      cannot be sentenced for homicide or accidental injury due to incapacity (Art. 6).
      The authors analyze these provisions with the aim of verifying if they are
      adequate to achieve the purposes that the legislator had set: 1) protecting
      patients' health; 2) offering psychiatrists clear rules of conduct in order to
      reduce the risk of being subjected to criminal proceedings. The first objective
      is endangered by the fact that the law does not indicate the level of the
      evidences trustworthiness necessary to make them be considered as binding
      guidelines. The second objective appears unreachable. In fact, the law under
      consideration states that only incapacity is not punishable, whereas homicide and
      lesions caused by negligence or imprudence, even if slight, are considered a
      crime. In the psychiatric field, more than in other branches of medicine, charges
      normally concern negligence or imprudence. Therefore, this reform does not limit
      at all psychiatrists' criminal liability.

PMID- 29343871
TI  - [Ulysses contract in psychiatry].
AB  - Over the last twenty years we have witnessed a growing focus on the rights of the
      ill people. The debate on informed consent and a new redefinition of the
      therapeutic relationship is constantly evolving. With this article, we propose a
      critical literature review of the so-called "Ulysses contract" or "psychiatric
      advance directives". It refers to the will that a subject expresses in writing,
      or orally, about the treatments he or she wishes or does not wish to be subject
      to if the time comes when it may be impossible to express his/her consent. This
      can especially occur in those with psychiatric disorders with serious clinical
      involvement and remitting-relapse (typically bipolar disorder, but also chronic
      delusional disorders and schizophrenia). In this context, the question is whether
      during intercritical periods the patient may or may not leave instructions to
      their care-givers. This aspect opens up to a series of interdisciplinary
      problems. In this article, we want to show the complexity of this debate from a
      clinical, ethical, legal and psychodynamic point of view, emphasizing the
      strengths and the major criticisms of the psychiatric advance directives for each
      area.

PMID- 29343872
TI  - [Duties and liabilities for psychiatrists].
AB  - This paper evaluates forensic duties and liabilities for psychiatrists, based on
      the current literature and based on our experience over several years of forensic
      medicine practice, involving both criminal and civil cases. We evaluated
      different scenarios, including cases of patients dangerous to themselves or
      others. We highlighted the importance to keep adequate and detailed clinical
      records, both in the inpatient and outpatient setting, given the absence of other
      objective items (e.g., laboratory records or other instrumental assessments) that
      may be of help for the judge and his/her counselors.

PMID- 29343873
TI  - A bibliometric analysis of scientific production on atypical antipsychotic drugs
      from Italy
AB  - Objective: A bibliometric study of peer-reviewed scientific publications on
      atypical antipsychotic drugs (AADs) from Italy is herein presented. Methods: We
      selected the documents from Scopus database. We applied several bibliometric
      indicators of production and dispersion, including Price's Law about the increase
      of scientific literature, and Bradford's Law. We also calculated the
      participation indexacross different countries. The bibliometric data have also
      been correlated with some social and health data sourcing in Italy, such as total
      per capita expenditure on health and gross domestic expenditure. Results: A total
      of 2949 original documents were published within the period 1972-2015. Our
      results state fulfilment of Price's Law, with scientific production showing
      exponential growth (r=0.901, as against an r=0.838 after linear adjustment). The
      drugs most widely studied were clozapine (257 documents), risperidone (179), and
      olanzapine (172). Stratificationinto Bradford zones yielded a nucleus represented
      by the Journal of Clinical Psychopharmacology and Rivista di Psichiatria (58
      articles, each one). A total of 1091 different journals were evaluated.
      Conclusions: The publications on AADs in Italy have undergone exponential growth
      over the studied period, which is in line with the progressively burgeoning on
      novel AAD releases. No evidence of saturation point was observed.

PMID- 29343874
TI  - [Mental Health Recovery Star: features and validation study of the Italian
      version].
AB  - AIM: Mental Health Recovery Star (MHRS) is an instrument that helps to assess
      recovery processes of mental health patients through a collaborative approach.
      The aim of the study is to describe the features of the instrument and to report
      the results of the Italian validation study. METHODS: The study involved 117
      users which were evaluated in two phases. Besides MRHS, HoNOS, WHOQoL-brief, GAF
      were used. Acceptability for users and key-workers of the instruments and its
      main psychometric properties, as test-retes (ICC) and concurrent validity
      (Pearson's correlation coefficient), were evaluated. RESULTS: MHRS showed to have
      temporal stability in all its areas. Significant correlations were found between
      the MHRS and the most closely related areas of the scales used. Inter-rater
      reliability were studied in an unsatisfactory way. MHRS was appreciated and easy
      to use. Collaborative evaluations were completed mostly in less than 45 minutes.
      CONCLUSIONS: MHRS is an acceptable tool for users and staff-members,
      distinguishing itself from the use of useful visual aids; helps to identify the
      patient's recovery path and supports a collaborative approach between user and
      operator. The results of the psychometric properties of the instrument appeared
      promising but not exhaustive. Although further efforts should be addressed to the
      implementation of such aspects of the instrument and reflections should be raised
      with respect to the traditional methods to detect the complex meaning of recovery
      (subjective-objective aspects), the valuable collaborative contribution of MHRS
      can not be denied in favoring the user's responsibility and supporting the
      professional worker in his role of case manager.

PMID- 29343875
TI  - [Trazodone prolonged release in bipolar disorder II-obsessive-compulsive disorder
      comorbidity: a case report].
AB  - Approximately 21% of patients with bipolar disorder (BD) also have an additional
      diagnosis of obsessive-compulsive disorder (OCD). This condition is associated
      with a more severe prognosis and complicates the treatment of BD. In our case
      report we provide documentary evidence of our experience with trazodone prolonged
      release in the treatment of depressive phase in a patient with BD II-OCD
      comorbidity. Rationality in the choise of treatment was based on the need to
      manage depressive and obsessive symptoms without facilitating hypomania switches.

PMID- 29343878
TI  - CXCL14-like Immunoreactivity Exists in Somatostatin-containing Endocrine Cells,
      and in the Lamina Propria and Submucosal Somatostatinergic Nervous System of
      Mouse Alimentary Tract.
AB  - In the present study, we investigated the distribution of CXCL14 immunoreactive
      endocrine cells and neurons in mouse alimentary tract by immunohistochemistry.
      CXCL14 immunoreactive endocrine cells were found as closed-type cells in the
      stomach and open-type cells in the small intestine. The immunostaining of these
      endocrine cells corresponded with that of the somatostatin-containing endocrine
      cells. Only a few CXCL14 immunoreactive endocrine cells were seen in the large
      intestine. CXCL14 immunoreactive fibers were observed in the muscular layer from
      the stomach to the rectum with most abundance in the rectum. Many CXCL14
      immunoreactive fibers were observed in the lamina propria and submucosal layer
      from the duodenum to the rectum with most abundance in the rectum; these fibers
      corresponded to the somatostatin-containing nerve fibers. Some CXCL14
      immunoreactive neuronal somata that were also immuno-positive for somatostatin,
      were noted in the submucosal layer of the rectum. However, the remaining parts of
      the alimentary tract presented with almost negligible immunoreactive somata. The
      co-localization of CXCL14 and somatostatin suggests that CXCL14 contributes to
      the function of somatostatin, which include the inhibition of other endocrine and
      exocrine cells and the enteric nervous systems.

PMID- 29343879
TI  - CCN3 Expression Marks a Sulfomucin-nonproducing Unique Subset of Colonic Goblet
      Cells in Mice.
AB  - Intestinal goblet cells are characterized by their unique morphology and
      specialized function to secrete mucins. Although it is known that they are a
      heterogeneous population of cells, there have been few studies that relate the
      expression of a particular gene with functionally distinct subpopulations of
      intestinal goblet cells. Here we show that CCN3, a gene encoding a member of the
      CCN family proteins, is induced by inhibition of Notch signaling in colonic
      epithelial cells and expressed in goblet cells in mice. We demonstrate that CCN3
      expression is confined to a subpopulation of goblet cells in the lower crypt of
      the proximal and middle colon. In addition, CCN3+ cells in the colon correlate
      well with the cells that are positive for alcian blue (AB) staining but negative
      for high-iron diamine (HID) staining in histology. We also show that CCN3+ cells,
      which are absent in the normal distal colon, transiently and ectopically emerge
      in regenerating crypts during the repair phase of DSS-induced colitis model. Our
      study thus suggests that CCN3 labels a unique subpopulation of sulfomucin
      nonproducing colonic goblet cells that function in both normal and diseased
      colonic epithelia.

PMID- 29343880
TI  - Novel Application of Loop-mediated Isothermal Amplification for Rapid Detection
      of Gene Translocation.
AB  - Identification of fusion genes in cancer is essential for pathological diagnosis
      and clinical therapy. Although methods for detection of fusion genes, such as
      fluorescence in situ hybridization (FISH) and real-time polymerase chain reaction
      (PCR), have been developed in last two decades, these methods are not ideal for
      detection of these genetic alterations owing to their high cost and time
      consuming procedures. In this study, we developed novel application for detection
      of gene translocations using loop-mediated isothermal amplification (LAMP). We
      verified the amplified DNA products of echinoderm microtubule-associated protein
      like 4 and anaplastic lymphoma kinase (EML4-ALK), synaptotagmin and synovial
      sarcoma, X breakpoint (SYT-SSX), and immunoglobulin heavy chain gene and B cell
      leukemia/lymphoma 2 (IgH/BCL2) by real-time PCR, agarose-gel electrophoresis, and
      the naked eye after the LAMP procedure. Fusion genes were detected in samples
      diluted 103 times within 60 min. Because of the advantages of rapid
      amplification, simple operation, and easy detection without requiring
      sophisticated equipment or technical skill, LAMP may have potential applications
      as an on-site analytical approach in hospitals for pathological diagnosis and
      decision making regarding appropriate therapeutic approachs.

PMID- 29343881
TI  - Validation of Anti-CSPalpha, SNAP25, Tyrosine Hydroxylase, Ubiquitin, Cleaved
      Caspase 3, and pSer PKC Motif Antibodies for Utilization in Western Blotting.
AB  - There are many commercial antibodies with little information provided by their
      suppliers as to their reliability. Accordingly, commercial antibodies require
      proper validation before being used in scientific research. In this study, we
      validated several commercial antibodies, including anti-CSPalpha, SNAP25,
      tyrosine hydroxylase, ubiquitin, cleaved caspase 3, and pSer PKC motif. Anti
      CSPalpha, SNAP25, and tyrosine hydroxylase antibodies could detect their
      endogenous target proteins with some degree of cross-reactivity. Furthermore,
      clear SNAP25 staining was observed with SNAP25 antibody. Antibodies directed
      against ubiquitin, cleaved caspase 3, and pSer PKC motif could detect poly
      ubiquitination, apoptosis, and phosphorylation, respectively.

PMID- 29343882
TI  - Can productivity and profitability be enhanced in intensively managed cereal
      systems while reducing the environmental footprint of production? Assessing
      sustainable intensification options in the breadbasket of India.
AB  - In the most productive area of the Indo-Gangetic Plains in Northwest India where
      high yields of rice and wheat are commonplace, a medium-term cropping system
      trial was conducted in Haryana State. The goal of the study was to identify
      integrated management options for further improving productivity and
      profitability while rationalizing resource use and reducing environmental
      externalities (i.e., "sustainable intensification", SI) by drawing on the
      principles of diversification, precision management, and conservation
      agriculture. Four scenarios were evaluated: Scenario 1 - "business-as-usual"
      [conventional puddled transplanted rice (PTR) followed by (fb) conventional-till
      wheat]; Scenario 2 - reduced tillage with opportunistic diversification and
      precision resource management [PTR fb zero-till (ZT) wheat fb ZT mungbean];
      Scenario 3 - ZT for all crops with opportunistic diversification and precision
      resource management [ZT direct-seeded rice (ZT-DSR) fb ZT wheat fb ZT mungbean];
      and Scenario 4 - ZT for all crops with strategic diversification and precision
      resource management [ZT maize fb ZT wheat fb ZT mungbean]. Results of this five
      year study strongly suggest that, compared with business-as-usual practices, SI
      strategies that incorporate multi-objective yield, economic, and environmental
      criteria can be more productive when used in these production environments. For
      Scenarios 2, 3, and 4, system-level increases in productivity (10-17%) and
      profitability (24-50%) were observed while using less irrigation water (15-71%
      reduction) and energy (17-47% reduction), leading to 15-30% lower global warming
      potential (GWP), with the ranges reflecting the implications of specific
      innovations. Scenario 3, where early wheat sowing was combined with ZT along with
      no puddling during the rice phase, resulted in a 13% gain in wheat yield compared
      with Scenario 2. A similar gain in wheat yield was observed in Scenario 4 vis-a
      vis Scenario 2. Compared to Scenario 1, wheat yields in Scenarios 3 and 4 were 15
      17% higher, whereas, in Scenario 2, yield was either similar in normal years or
      higher in warmer years. During the rainy (kharif) season, ZT-DSR provided yields
      similar to or higher than those of PTR in the first three years and lower (11
      30%) in Years 4 and 5, a result that provides a note of caution for interpreting
      technology performance through short-term trials or simply averaging results over
      several years. The resource use and economic and environmental advantages of DSR
      were more stable through time, including reductions in irrigation water (22-40%),
      production cost (11-17%), energy inputs (13-34%), and total GWP (14-32%). The
      integration of "best practices" in PTR in Scenario 2 resulted in reductions of
      24% in irrigation water and 21% in GWP, with a positive impact on yield (0.9
      t/ha) and profitability compared to conventional PTR, demonstrating the power of
      simple management changes to generate improved SI outcomes. When ZT maize was
      used as a diversification option instead of rice in Scenario 4, reductions in
      resource use jumped to 82-89% for irrigation water and 49-66% for energy inputs,
      with 13-40% lower GWP, similar or higher rice equivalent yield, and higher
      profitability (27-73%) in comparison to the rice-based scenarios. Despite these
      advantages, maize value chains are not robust in this part of India and public
      procurement is absent. Results do demonstrate that transformative opportunities
      exist to break the cycle of stagnating yields and inefficient resource use in the
      most productive cereal-based cropping systems of South Asia. However, these SI
      entry points need to be placed in the context of the major drivers of change in
      the region, including market conditions, risks, and declining labor availability,
      and matching with the needs and interests of different types of farmers.

PMID- 29343883
TI  - Magnetoelectric effect in nanogranular FeCo-MgF films at GHz frequencies.
AB  - The magnetoelectric effect is a key issue for material science and is
      particularly significant in the high frequency band, where it is indispensable in
      industrial applications. Here, we present for the first time, a study of the high
      frequency tunneling magneto-dielectric (TMD) effect in nanogranular FeCo-MgF
      films, consisting of nanometer-sized magnetic FeCo granules dispersed in an MgF
      insulator matrix. Dielectric relaxation and the TMD effect are confirmed at
      frequencies over 10 MHz. The frequency dependence of dielectric relaxation is
      described by the Debye-Frohlich model, taking relaxation time dispersion into
      account, which reflects variations in the nature of the microstructure, such as
      granule size, and the inter-spacing between the granules that affect the
      dielectric response. The TMD effect reaches a maximum at a frequency that is
      equivalent to the inverse of the relaxation time. The frequency where the peak
      TMD effect is observed varies between 12 MHz and 220 MHz, depending on the
      concentration of magnetic metal in the nanogranular films. The inter-spacing of
      the films decreases with increasing magnetic metal concentration, in accordance
      with the relaxation time. These results indicate that dielectric relaxation is
      controlled by changing the nanostructure, using the deposition conditions. A
      prospective application of these nanogranular films is in tunable impedance
      devices for next-generation mobile communication systems, at frequencies over 1
      GHz, where capacitance is controlled using the applied magnetic field.

PMID- 29343885
TI  - The curriculum: What is changing?

PMID- 29343884
TI  - Neutral Sphingomyelinase Behaviour in Hippocampus Neuroinflammation of MPTP
      Induced Mouse Model of Parkinson's Disease and in Embryonic Hippocampal Cells.
AB  - Neutral sphingomyelinase is known to be implicated in growth arrest,
      differentiation, proliferation, and apoptosis. Although previous studies have
      reported the involvement of neutral sphingomyelinase in hippocampus
      physiopathology, its behavior in the hippocampus during Parkinson's disease
      remains undetected. In this study, we show an upregulation of inducible nitric
      oxide synthase and a downregulation of neutral sphingomyelinase in the
      hippocampus of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine- (MPTP-) induced
      mouse model of Parkinson's disease. Moreover, the stimulation of neutral
      sphingomyelinase activity with vitamin 1,25-dihydroxyvitamin D3 reduces
      specifically saturated fatty acid sphingomyelin by making sphingomyelin a less
      rigid molecule that might influence neurite plasticity. The possible biological
      relevance of the increase of neutral sphingomyelinase in Parkinson's disease is
      discussed.

PMID- 29343886
TI  - Prof. Narendra J. Pandya.

PMID- 29343887
TI  - Synovial tuberculosis of the hand: An ancient disease in an unusual localisation.
AB  - Background: Tuberculosis is the most prevalent infectious disease in the world.
      It is mainly caused by Mycobacterium tuberculosis. Osteoarticular tuberculosis
      represents 1%-3%. Tenosynovitis is the most common form of the disease in the
      hand. Aims: The aim of this study is to present an update of synovial
      tuberculosis. Materials and Methods: The authors present a literature review, the
      clinical and surgical management and case reports. Results: The outcomes were
      satisfactory and were not report complications. Conclusions: Early diagnosis,
      surgical transection of the transverse carpal ligament, debridement and complete
      excision of the infected synovium may be required, along with antituberculosis
      drugs. Knowledge of this disease in the hand can provide a better diagnosis and
      outcome.

PMID- 29343888
TI  - Medial femoral condyle vascularised corticoperiosteal graft: A suitable choice
      for scaphoid non-union.
AB  - Introduction: Scaphoid fractures are not very common and frequently remain
      undiagnosed, presenting in non-union and persistent wrist pain. Options for
      scaphoid fracture treatment have been described over several decades, however,
      none with an optimal solution to achieve union along with good hand function. We
      describe here, the use of vascularised corticoperiosteal bone grafts from the
      medial femoral condyle (MFC) as a solution for the difficult problem of scaphoid
      fracture non-union. Materials and Methods: This series has 11 patients with non
      union following a scaphoid fracture treated over 18 months ranging from January
      2014 to January 2016 using a vascularised corticoperiosteal graft from the MFC.
      Bone graft fixation was done using K-wires and anastomosis was done with the
      radial vessels. Results: There were no cases of flap loss. Time of union was an
      average 3 months. All patients had a full range of movements. Discussion: MFC is
      an ideal site for harvesting vascularised corticoperiosteal grafts providing a
      large surface of tissue supplied by a rich periosteal plexus from the descending
      genicular artery. No significant donor site morbidities have been reported in any
      series in the past. The well-defined anatomy helps in a rather simple dissection.
      Corticoperiosteal grafts have a high osteogenic potential and hence, this
      vascularised graft seems ideal for small bone non-unions. Conclusion: Thin,
      pliable and highly vascularised corticocancellous grafts can be obtained from the
      MFC as an optimal treatment option for scaphoid non-unions.

PMID- 29343889
TI  - First two bilateral hand transplantations in India (Part 1): From vision to
      reality.
AB  - Introduction: Vascularized composite tissue allotransplantation is a relatively
      new concept, which was unavailable in the Indian subcontinent till a bilateral
      hand transplant was carried out successfully in January 2015. Materials and
      Methods: The setting up of the transplant programme involved obtaining legal
      clearances, creating public awareness, harnessing the institutional facilities,
      drawing up protocols, assembling the surgical team, managing immunological
      issues, rehabilitation and preparing the ancillary services. Results: Both, the
      first and second bilateral hand transplants were resounding successes with both
      the recipients getting back to their original daily routines. Conclusions: The
      organisation of the hand transplant programme was a large task, which
      necessitated intensive planning, and cooperation from various teams within and
      outside the institution. Exemplary team-work was the key to the phenomenal
      success of these path breaking endeavors in the subcontinent.

PMID- 29343890
TI  - First two bilateral hand transplantations in India (Part 2): Technical details.
AB  - Introduction: This article deals with two patients who underwent bilateral hand
      transplantation following amputation of both upper limbs at the distal third of
      the foream. Materials and Methods: The first patient had a history of loss of
      hands in a train accident , with possiblity of a run over element during the
      injury. The second patient lost his both hands in a mine blast. The preoperative
      work up included detailed clinical and psychological evaluation. The donor
      retrieval was similar in both the cases and the donors were housed in our own
      instittution. The donor preparation, recipient preparation and the transplant
      procedure was similar except for the need of primary tendon transfers in the left
      hand of the first patient. Results: The first patient needed a free flap transfer
      to cover compromised skin flap on the left hand on the second day. The second
      hand transplant was uneventful. Both the recipients are now back to their normal
      daily routines. Conclusions: Hand transplantation is a potentially life altering
      procedure, but to optimise the results, it is imperative that there is a
      meticulous planning and diligent execution with utmost importance to the detail
      coupled with a synchronised team effort.

PMID- 29343891
TI  - First two bilateral hand transplantations in India (Part 3): Rehabilitation and
      immediate outcome.
AB  - Introduction: This report covers the strategies adopted for rehabilitation for
      the first and second dual hand transplants performed in India. Materials and
      Methods: The team, under a trained physiatrist, including physiotherapy and
      occupational therapy personnel, was involved in the management of both these
      patients. The management protocol was developed considering previous reports as
      well as our management strategies in the rehabilitation of the replanted hands.
      The involvement of the team with the patients started in the 1st week itself and
      continued on a daily basis for the entire year. Results: Outcome analysis was
      performed at 6 months and 1 year using the disability of shoulder and hand
      evaluation and hand transplant scoring system. Functional magnetic resonance
      imaging was done at the end of 1 year to assess the cortical integration of the
      transplanted hand. Conclusion: Despite more than 110 hands being transplanted
      worldwide, hand transplant remains an experimental procedure. It is still not
      considered the "standard of care" for hand amputees. Outcome analyses performed
      worldwide do indicate that the procedure can provide a substantial improvement in
      the quality of life for the hand amputee, especially the bilateral amputees.

PMID- 29343892
TI  - First two bilateral hand transplantations in India (Part 4): Immediate post
      operative care, immunosuppression protocol and monitoring.
AB  - Introduction: Being able to counter immune-mediated rejection has for decades
      been the single largest obstacle for the progress of vascular composite
      allotransplantation (VCA). The human immune system performs the key role of
      differentiating the 'self ' from the 'non-self '. This, although is
      quintessential to eliminate or resist infections, also resists the acceptance of
      an allograft which it promptly recognises as 'non-self'. Materials and Methods:
      Pre-operative evaluation of the recipient evaluation included immunological
      assessment in the form of panel reactive antibodies (PRA), human leucocyte
      antigen (HLA) typing, donor-specific antibody detection assays (DSA) and
      complement-dependent cytotoxicity assays (CDC). Induction immunosuppression was
      by thymoglobulin and the maintenance by the standard triple-drug therapy.
      Results: Both the recipients were managed by the standard triple drug therapy and
      have had only minor episodes of rejections thus far which have been managed
      appropriately. Discussion: Induction immunosuppression was by thymoglobulin and
      the maintenance by the standard triple-drug therapy. Various groups have tried
      various other formulations and regimes as well. Conclusion: A comprehensive plan
      has to be drawn up for immunological screening, selection and the post-operative
      immunosuppressant usage. The ultimate goal of these immunosuppression modalities
      is to achieve a state of donor-specific tolerance.

PMID- 29343893
TI  - Assessment of perfusion of free flaps used in head and neck reconstruction using
      pulsatility index.
AB  - Objective: To detect venous or arterial obstruction in the pedicle of a free flap
      we can monitor resistance in the flap bed which is reflected in Pulsatility Index
      (PI) Therefore if we detect change in the values of the PI in these flaps then we
      can detect complications in flap due to vascular insufficiency early. Materials
      and Methods: Seven patients of Free Fibular Flap Reconstruction and ten patients
      of Free Radial Forearm Flap reconstruction were evaluated over a period of 18
      months. In the pre op we recorded PI of Radial and Peroneal artery using colour
      doppler study. In the Post Operative Period 2 readings of PI at the anastomotic
      site were taken on Day 1 and Day 7. Results: Both Free Radial Forearm and Free
      Fibula flaps which were healthy (n = 15) showed a significant decrease in PI
      values on first Post Op day as compared to Pre Op. Also there was a significant
      fall in PI on Post Op Day 7 as compared to post op Day 1 (P < 0.05) in these
      flaps. The flaps developing complications (n = 2) had significantly higher Day 1
      Post op PI readings as compared to healthy flaps (P < 0.05). Conclusion: PI is an
      objective index which can indicate changes in perfusion of free flaps used in
      Head and Neck reconstruction based on which we can predict if a flap is
      susceptible to circulatory compromise.

PMID- 29343894
TI  - Primary unilateral cleft lip nasal deformity repair using V-Y-Z plasty: An
      anthropometric study.
AB  - Background: Secondary nose deformity after unilateral cleft lip repair is a
      common problem. Loss of tip projection on the cleft side of unilateral cleft lip
      nasal deformity can be difficult to correct due to lack of adequate support. The
      purpose of this study is to evaluate the surgical outcome after using V-Y-Z
      plasty to address unilateral cleft lip nasal deformities. Methods: A cross
      sectional study of one surgeon's outcome of 58 performed primary complete
      unilateral cleft lip nasal deformity repairs. All these patients met the study
      criterion of having anthropometric measurements at the cleft and non-cleft side
      of the nose performed at least 1 year postoperatively. Results: Since 2012, 32
      consecutive patients have undergone primary anatomical repair of the cleft nasal
      deformity in patients with a complete unilateral cleft. We have not found
      statistically significant differences between the cleft and non-cleft nostril
      dome height and columella length measured at least 1 year postoperatively.
      Conclusions: The findings suggest that the V-Y-Z plasty is a good alternative to
      create a more symmetric nasal tip in patients with primary unilateral cleft lip
      nasal deformity. Additional studies are required to evaluate functional and long
      term outcomes after primary rhinoplasty in patients with unilateral cleft lip.

PMID- 29343895
TI  - Why borrow from Peter when Paul can afford it? Reverse homodigital artery flap
      for fingertip reconstruction.
AB  - Background: Fingertip injuries that are complicated by pulp loss, bone or tendon
      exposure will need a flap cover. Cross finger flap is commonly used to cover such
      defects. However, patients are apprehensive about injuring the uninjured finger
      as a donor site. Reverse homodigital artery flap (RHAF) can provide reliable
      vascularised cover to such defects. Aims: This study aims to assess the
      functional and aesthetic outcomes along with the patient satisfaction of RHAFs
      done for fingertip defects. Materials and Methods: RHAFs done in 18 patients
      operated between August 2015 and October 2016 were retrospectively analysed on
      flap survival, sensory recovery, range of movements, hypersensitivity, cold
      intolerance, flexion contracture and donor site morbidity. Results: Seventeen of
      the 18 flaps done survived completely. One flap had partial necrosis of 3 mm that
      healed conservatively. Middle finger of the right hand was the most commonly
      injured finger. Touch, pain and pressure sensations recovered in 8-12 weeks. Two
      point discrimination was 4.5 mm at 6 months. The deficit of 5 degrees  s was
      present at distal interphalangeal joint during active flexion at 6 months. Cold
      intolerance and flexion contracture were not seen and 2 instances of
      hypersensitivity at 2 months got cured conservatively after 4 months. Overall
      satisfaction of patients was 8/10. Conclusion: RHAF provides single staged well
      vascularised cover for fingertip injuries with good sensory recovery without
      damaging the adjacent uninjured finger. Hence, it can be a reliable flap for
      fingertip reconstruction in selected cases.

PMID- 29343896
TI  - Management of vascular anomalies: Review of institutional management algorithm.
AB  - Introduction: Vascular anomalies are congenital lesions broadly categorised into
      vascular tumour (haemangiomas) and vascular dysmorphogenesis (vascular
      malformation). The management of these difficult problems has lately been
      simplified by the biological classification and multidisciplinary approach. To
      standardise the treatment protocol, an algorithm has been devised. The study aims
      to validate the algorithm in terms of its utility and presents our experience in
      managing vascular anomalies. Materials and Methods: The biological classification
      of Mulliken and Glowacki was followed. A detailed algorithm for management of
      vascular anomalies has been devised in the department. The protocol is being
      practiced by us since the past two decades. The data regarding the types of
      lesions and treatment modality used were maintained. Results and Conclusion: This
      study was conducted from 2002 to 2012. A total of 784 cases of vascular anomalies
      were included in the study of which 196 were haemangiomas and 588 were vascular
      malformations. The algorithmic approach has brought an element of much-needed
      objectivity in the management of vascular anomalies. This has helped us to define
      the management of particular lesion considering its pathology, extent and
      aesthetic and functional consequences of ablation to a certain extent.

PMID- 29343897
TI  - Contralateral lumbo-umbilical flap: A versatile technique for volar finger
      coverage.
AB  - Background: While contemplating any difficult soft tissue reconstruction, patient
      comfort and compliance is of paramount importance. Reconstruction of the volar
      aspect of fingers and hand by the ipsilateral pedicled flaps (groin flap,
      abdominal flaps) is demanding as the flap inset is difficult for the surgeon and
      very uncomfortable for the patient. This often leads to flap complications. For
      the comfort of the patient, better compliance and ease of complete inset, we
      planned to manage soft tissue defects of the volar aspect of fingers and hand by
      a new contralateral pedicled lumbo-umbilical flap. This flap is based on the
      paraumbilical perforators of deep inferior epigastric artery. Materials and
      Methods: The contralateral pedicled lumbo-umbilical flap was used in eight
      patients with high-tension electrical burn injuries involving the volar aspect of
      fingers and hand. The patients were closely observed for first 6 weeks for any
      flap or donor site complications and then followed monthly to assess donor and
      recipient site characteristics for 6 months to 2 years. Results and Conclusion:
      Large flaps up to 8 cm * 16 cm were raised. All but one flaps survived
      completely. All patients were mobilised within 48 h and five were discharged in
      less than a week after initial inset. The flap is reliable, easy to harvest and
      easy to inset on the volar aspect of fingers. The arm is positioned in a very
      comfortable position. The main disadvantage, however, is a conspicuous abdominal
      scar.

PMID- 29343898
TI  - Assessment of temporomandibular joint dysfunction in condylar fracture of the
      mandible using the Helkimo index.
AB  - Introduction: Condylar fractures of the mandible are functionally important
      fractures as the condyle of the mandible being a part of the temporomandibular
      joint (TMJ) and can lead to TMJ dysfunction if not properly treated. Materials
      and Methods: This was a cross-sectional study of a total of 33 treated patients
      with fracture of the mandibular condyle who underwent examination as per the
      Helkimo index. Their dysfunction was quantified and clinicoepidemiological
      characteristics were assessed. It was found that majority of our patients were
      young males involved in a two-wheeler accident. All patients underwent
      intermaxillary fixation as the minimum treatment and 30% underwent open reduction
      and internal fixation in addition. Results: There was no statistically
      significant association between the degree of clinical dysfunction and factors
      such as age, mechanism of injury, type of condyle fracture, presence of other
      mandible fractures, and surgical procedure. However, dislocation of the
      mandibular condyle was found to be a negative prognostic factor and all these
      patients had some degree of dysfunction. Conclusion: The overall prevalence of
      TMJ dysfunction according to the Helkimo index was 90%. About 61% of patients had
      mild dysfunction (Di1) and 30% had moderate dysfunction (Di2). None of the
      patients had severe dysfunction. To conclude, the Helkimo index is a simple,
      effective, inexpensive, reliable screening index to assess TMJ dysfunction in
      condylar fractures of mandible.

PMID- 29343899
TI  - Flap cover in a patient with severe haemophilia type A.
AB  - Haemophilia A is a rare haematological disorder due to deficiency of Factor VIII,
      causing an abnormal coagulation response to injury. In severe haemophilia A,
      Factor VIII level is < 1%, often manifesting with spontaneous bleeding into
      joints. Judicious use of recombinant Factor VIII therapy to maintain adequate
      levels in the intraoperative, immediate and late post-operative periods, together
      with adjuvant pro-coagulants, can ensure a safe outcome following surgery. We
      describe the successful management of one such patient suffering from Marjolin's
      ulcer of the right gluteal region, who needed wide local excision followed by
      flap cover. A protocol for management of such patients is also suggested. This is
      the first such case report from the Indian subcontinent, with only a few such
      published reports from the West.

PMID- 29343900
TI  - Direct electrical injury to brachial plexus.
AB  - Electrical current can cause neurological damage directly or by conversion to
      thermal energy. However, electrical injury causing isolated brachial plexus
      injury without cutaneous burns is extremely rare. We present a case of a 17-year
      old boy who sustained accidental electrical injury to left upper extremity with
      no associated entry or exit wounds. Complete motor and sensory loss in upper limb
      were noted immediately after injury. Subsequently, the patient showed partial
      recovery in muscles around the shoulder and in ulnar nerve distribution at 6
      months. However, there was no improvement in muscles supplied by
      musculocutaneous, median and radial nerves. On exploration at 6 months after
      trauma, injury to the infraclavicular plexus was identified. Reconstruction of
      musculocutaneous, median and radial nerves by means of sural nerve cable grafts
      was performed. The patient has shown excellent recovery in musculocutaneous nerve
      function with acceptable recovery of radial nerve function at 1-year post-injury.

PMID- 29343901
TI  - A modified Lund and Browder chart.

PMID- 29343902
TI  - An axillary port with concealed scar for liposuction of gynaecomastia.

PMID- 29343903
TI  - Whose evidence do we follow?

PMID- 29343904
TI  - Medical Council of India's amended qualifications for Indian medical teachers:
      Well intended, yet half-hearted.

PMID- 29343905
TI  - What's inside.

PMID- 29343906
TI  - Round up.

PMID- 29343907
TI  - New therapies in nonmuscle invasive bladder cancer treatment.
AB  - Introduction: Nonmuscle invasive bladder cancer (NMIBC) remains a very
      challenging disease to treat with high rates of recurrence and progression
      associated with current therapies. Recent technological and biological advances
      have led to the development of novel agents in NMIBC therapy. Methods: We
      reviewed existing literature as well as currently active and recently completed
      clinical trials in NMIBC by querying PubMed.gov and clinicaltrials.gov. Results:
      A wide variety of new therapies in NMIBC treatment are currently being developed,
      utilizing recent developments in the understanding of immune therapies and cancer
      biology. Conclusion: The ongoing efforts to develop new therapeutic approaches
      for NMIBC look very promising and are continuing to evolve.

PMID- 29343909
TI  - Decline in semen parameters from 2000 to 2016 among Bangladeshi men attending a
      tertiary care hospital.
AB  - Introduction: The objective of this study was to analyze longitudinal changes in
      sperm parameters of Bangladeshi men. We hypothesized that semen parameters
      declined for this population. Methods: We retrospectively analyzed semen data
      from men aged 18-64 years who sought care for general sperm quality or updates on
      fertility status at an infertility clinic in Dhaka, Bangladesh, from January 2000
      to June 2016 (n = 13,953). Samples with incomplete data were excluded (n = 143).
      The WHO normal criteria and semen analysis procedures were used to evaluate
      parameters of the remaining 13,810 specimens. Samples with missing values on
      sperm concentration (n = 6187) were excluded from concentration analyses. Age and
      duration of abstinence at testing were recorded and adjusted for. Data were
      imported into SAS(r) 9.4 statistical software. Temporal significance was
      investigated using one-way ANOVA for motility parameters and Chi-square test for
      raw concentration. Logistic regression analyzed the effects of confounders on
      azoospermia and raw concentration, while median regression modeling adjusted
      confounders for concentration, total motility, and rapid linear (RL) motility.
      Results: Age distribution was significantly correlated with annual parameter
      changes (concentration, total motility, and RL motility [P < 0.0001]). Adjusted
      total motility and RL motility declined by 20% from their maximum values to end
      of the study (P < 0.0001). Raw concentration lacked clear trends and was
      unaffected by adjustment. Azoospermia increased by 18% between the 2000-2010 and
      2011-2016 participants (odds ratio = 0.16 [0.14-0.16]). Conclusion: In agreement
      with the hypothesis, Bangladeshi males attending this clinic have experienced
      decline in semen parameters (total motility and RL motility) and increased
      frequency of azoospermia.

PMID- 29343908
TI  - PET-CT and PET-MR in urological cancers other than prostate cancer: An update on
      state of the art.
AB  - Hybrid positron emission tomography with computed tomography (PET/CT) and
      magnetic resonance imaging (PET/MRI) have enabled the combination of morphologic
      and functional imaging with the promise of providing better information in
      guiding therapy. Further advance has been made in the past decade with the
      development of newer radiotracers and optimization of the technical aspects. We
      performed a search in PubMed, Scopus, and Google Scholar for peer-reviewed
      literature concerning the advances and newer developments in the imaging of
      nonprostate urologic cancers between 2005 and 2017. This review aims at
      summarizing the current evidence on PET imaging in nonprostate urologic cancers
      and their impact on the diagnosis, staging, prognostication, response assessment,
      and restaging of these malignancies. However, much of the evidence is still in
      infancy and has not been incorporated into routine management or the practice
      guidelines of National Comprehensive Cancer Network or European Society for
      Medical Oncology (ESMO).

PMID- 29343910
TI  - Urodynamic outcomes of tamsulosin in the treatment of primary bladder neck
      obstruction in men.
AB  - Introduction: Alpha blockers are widely used in the treatment of primary bladder
      neck obstruction; however, evidence for objective urodynamic efficacy is scarce.
      We studied the effect of the uroselective alpha1-blocker tamsulosin on urodynamic
      parameters in male patients with type I primary bladder neck obstruction.
      Methods: A single center prospective observational study was carried out from
      July 2013 to February 2015. Male patients (18-50 years) with type 1 primary
      bladder neck obstruction were recruited. Selected patients were started on tablet
      tamsulosin 0.4 mg once daily for 3 months. International prostate symptom score
      (IPSS), uroflow and urodynamic studies were done pre- and post-treatment. Primary
      outcome was decreased in minimum detrusor pressure at maximum flow rate by 15%.
      Wilcoxon-matched pair signed-rank test was used. Results: Of 39 patients
      recruited, 21 patients completed the follow-up as per protocol and were analyzed.
      Mean age was 41 years. 57% patients achieved the primary outcome (median detrusor
      pressure pre- and post-treatment were 71 and 56 cm of water, P < 0.001).
      Similarly, median values for bladder outlet obstruction index (BOOI) and IPSS
      decreased from 59 to 38 (P < 0.001) and 22 to 12 (P < 0.001), respectively.
      Median maximum flow rate increased from 8 to 10 ml (P = 0.05). Pretreatment BOOI
      of >60 was associated with poor outcomes. Conclusions: Tamsulosin 0.4 mg once a
      day is effective in reducing bladder outlet obstruction on pressure flow studies
      in patients with primary bladder neck obstruction type 1.

PMID- 29343911
TI  - Oncologic outcomes in patients with nonurothelial bladder cancer.
AB  - Introduction: We aimed to evaluate the relative prognostic impact of the most
      common variant histologies on disease-specific survival (DSS) in patients
      undergoing radical cystectomy. Materials and Methods: The Surveillance,
      Epidemiology, and End Result database was used to identify patients who underwent
      radical cystectomy for bladder cancer from 1990 to 2007. Patients with urothelial
      cell carcinoma (UCC), squamous cell carcinoma (SCC), adenocarcinoma (AC),
      sarcoma, small cell carcinoma, signet ring carcinoma, and spindle cell carcinoma
      were included in the study. Multivariable analysis was performed using Cox
      proportional hazards model to assess independent predictors of disease-specific
      survival (DSS). Mortality rates were estimated using Kaplan-Meier analyses.
      Results: A total of 14,130 patients met inclusion criteria with the following
      histologies: UCC (90.1%), SCC (4.6%), AC, (2.3%), sarcoma (0.8%), small cell
      carcinoma (0.8%), signet ring carcinoma (0.5%), and spindle cell carcinoma
      (0.9%). Three-year DSS was most favorable in patients with UCC (63.7%; 95%
      confidence interval [62.9%-64.8%]) and AC (65.3% [59.3%-70.6%]), whereas 3-year
      DSS was the least favorable for small cell carcinoma (41.6% [31.3%-51.6%]) and
      sarcoma (45.4% [35.1%-55.1%]). In the multivariable analysis, independent
      predictors of DSS were age, marital status, grade, T-stage, N-stage, and variant
      histology. With respect to UCC, there was an increased risk of disease-specific
      death associated with all variants except AC. Sarcoma and spindle cell carcinoma
      were associated with the highest risk of death. Conclusions: With the exception
      of AC, the most common variant bladder cancer histologies are all independently
      associated with worse DSS relative to UCC in patients undergoing radical
      cystectomy.

PMID- 29343912
TI  - Lateral percutaneous nephrolithotomy: A safe and effective surgical approach.
AB  - Introduction: Percutaneous nephrolithotomy (PCNL) is traditionally performed with
      the patient in the prone position for large renal calculi. However, anesthetic
      limitations exist with the prone position. Similarly, the supine position is
      associated with poorer ergonomics due to the awkward downward position of the
      renal tract, a smaller window for percutaneous puncture, and a higher risk of
      anterior calyx puncture. This study aimed to demonstrate the feasibility and
      safety of lateral-PCNL in managing large renal calculi without the disadvantages
      of prone and supine positions. Methods: Retrospectively, 347 lateral-PCNL cases
      performed from July 2001 to July 2015 were examined. the patient's thorax,
      abdomen, and pelvis were positioned over a bridge perpendicular to a "broken"
      table, creating an extended lumbodorsal space. The procedure was evaluated in
      terms of stone clearance at 3 months' postprocedure, operative time, and
      complications. Results: Primary stone clearance was achieved in 82.7% of
      patients. The mean operating time was 97 min. The average time taken to establish
      the tract and mean radiation time were 4.5 min and 6.93 min, respectively. In
      total, 2.3% of patients required postoperative transfusion, and 13.5% of patients
      had postoperative fever. There was one case of hydrothorax, but no bowel
      perforation. Conclusions: Our lateral-PCNL technique allows for effective stone
      clearance due to good stone ergonomics and it should be considered as a safe
      alternative even in the most routine procedures.

PMID- 29343913
TI  - Comparison of RENAL, PADUA, and C-index scoring systems in predicting
      perioperative outcomes after nephron sparing surgery.
AB  - Introduction and Objective: The RENAL, PADUA and centrality index (C-index)
      nephrometry scoring systems (SS) have been individually evaluated for their role
      in predicting trifecta outcomes after nephron-sparing surgery (NSS). However,
      there is little data on their comparative superiority. The present study was
      designed to evaluate the predictive value of three SS and to assess interobserver
      reliability. Materials and Methods: Fifty patients undergoing NSS at our center
      between January 2014 and April 2016 were included in the study. The demographic
      details were noted. Images (computed tomography [CT] scans or magnetic resonance
      imaging) were reviewed by a urologist and a radiologist independently and RENAL,
      PADUA, and C-index were calculated. The correlation between these scoring system
      and trifecta outcomes were calculated. Results: The RENAL and PADUA score did not
      correlate with any of the perioperative parameters. However, C-index had a
      significant correlation with operative time (OT) (P = 0.02) and trifecta outcomes
      (P < 0.05). There was an excellent concordance between the two observers in
      scoring the RENAL score (alpha = 0.915; intraclass correlation coefficient [ICC]
      = 0.814) and PADUA score (alpha = 0.816; ICC = 0.689 [P < 0.001]). There was
      lesser although acceptable concordance in the calculation of C-index (ICC -0.552;
      alpha -0.711). Conclusions: There is good correlation among all the 3 SS. C-index
      has lower reproducibility due to difficult mathematical calculation but
      correlated best with trifecta outcomes.

PMID- 29343914
TI  - Symptomatic lower urinary tract dysfunction in sacral agenesis: Potentially high
      risk?
AB  - Introduction: Sacral agenesis (SA) is a caudal regression anomaly that can cause
      neurogenic bladder but is not generally recognized as high risk. We studied the
      clinical presentation, upper urinary tract, bone and spine abnormalities, and
      urodynamic findings in patients with SA and compared them with related high-risk
      conditions, anorectal malformation (ARM), and cloacal malformation. Materials and
      Methods: Patient records between May 2011 and December 2015 were identified and
      grouped into isolated SA without an overt anomaly (Group I), SA with overt caudal
      regression anomalies (Group II), and ARM or cloacal malformation without the SA
      (Group III). Distribution of clinical and urodynamic findings and factors
      associated with reduced eGFR were tested with rank sum test, t-test, and
      unadjusted odds (P < 0.05 significant) using R statistical program (version
      3.1.3). Results: Of 605 neurogenic bladder patients treated in the study period,
      39 fulfilled the inclusion criteria. 12 were Group I, 5 Group II, and 22 Group
      III. Long-standing lower urinary symptoms were noted in all SA patients. Group I
      patients were older (14.5 years vs. 6 years and 5 years for II and III). Patients
      with SA (Group I and II) had poor compliance (6.7 ml/cmH2O, interquartile range
      [IQR] 4-13.6 ml/cmH2O), reduced age-adjusted bladder capacity (59%, IQR 22-85%),
      elevated end-fill pressure (22 cmH2O, IQR 11-28 cmH2O), hydronephrosis (88%), and
      reduction in eGFR (29%), all comparable to Group III. Most had Renshaw type II SA
      and tethered spinal cord rather than wedge-shaped termination. Limitations
      include small numbers and significant selection bias. Conclusions: Symptomatic
      neurogenic bladder due to SA may cause renal damage similar to ARM but often
      eludes diagnosis.

PMID- 29343915
TI  - Impact of learning curve on the perioperative outcomes following robot-assisted
      partial nephrectomy for renal tumors.
AB  - Introduction: Robot-assisted partial nephrectomy (RAPN) is an established,
      minimally invasive technique to treat patients with renal masses. The aim of this
      study was to assess the learning curve (LC) of RAPN, evaluate its impact on
      perioperative outcomes following RAPN and to study the role of surgeon experience
      in achieving "trifecta" outcomes following RAPN. Methods: We prospectively
      analyzed the clinical and pathological outcomes of 108 consecutive patients who
      underwent RAPN for renal tumors from January 2012 to December 2016 by a
      laparoscopy trained surgeon with no prior robotic experience. We used warm
      ischemia time (WIT) <20 min, operative time <120 min, and blood loss <100 ml as
      endpoints for plotting the LCs. Trifecta was analyzed in relation to our LC.
      Results: Surgeon experience was found to correlate with WIT, operative time, and
      blood loss. Overall 18.5% of patients developed complications. Complication rate
      reduced with increasing surgeon experience. LC was 44 cases for WIT <=20 min, 44
      cases for operative time <120 min, and 54 cases for blood loss <100 ml. Trifecta
      outcome was achieved in 67.6% patients overall and was found to correlate with
      increasing surgeon experience. Improvement in trifecta outcomes continued to
      occur beyond the LC. Conclusions: RAPN is a viable option for nephron-sparing
      surgery in patients with renal carcinoma. For a surgeon trained in laparoscopy,
      acceptable perioperative outcomes following RAPN can be achieved after an LC of
      about 44 cases. Increasing surgeon experience was associated with improved
      "trifecta" achievement following RAPN.

PMID- 29343916
TI  - Effects of tumor size and location on survival in upper tract urothelial
      carcinoma after nephroureterectomy.
AB  - Introduction: Upper Tract Urothelial Carcinoma (UTUC) is a rare disease with few
      prognostic determinants. We sought to evaluate the impact of tumor size and
      location on patient survival following nephroureterectomy for UTUC. Materials and
      Methods: Data on 8284 patients treated with radical nephroureterectomy for UTUC
      in the United States between 1998 and 2011 were analyzed from the National Cancer
      Data Base. Univariable survivorship curves were generated based on pT stage, pN
      stage, grade, tumor size, and tumor site (renal pelvis vs. ureter). A Cox
      proportional hazards model was used to evaluate the effect of age, comorbidity, T
      stage, lymph node involvement, tumor site, and tumor size on survival. Results:
      The median follow-up time was 46 months. A majority of the patients were male
      (55.4%) with a tumor size of >=3.5 cm (52.0%) and pT stage <T2 (47.8%). The
      overall 5 years survival overall survival (OS) for the entire cohort was 51.6%.
      When stratified by tumor size <3.5 cm or >=3.5 cm the 5-year OS was 45.9% and
      58.5%, respectively. On multivariable analysis controlling for age, Charlson
      comorbidity index, grade, and tumor stage, tumor size >=3.5 cm was independently
      predictive of worse OS (odds ratio: 1.13 [95% confidence interval: 1.02-1.26], P
      = 0.023). Conclusions: Using the largest series of patients with UTUC undergoing
      nephroureterectomy, we demonstrated a worse survival in patients with larger
      tumor sizes (>=3.5 cm) but no difference in survival based on tumor location
      while controlling for other pathologic characteristics. Incorporation of tumor
      size into perioperative risk modeling may help with patient stratification and
      provide further prognostic information for patient counseling.

PMID- 29343917
TI  - Editorial comment on "Effects of tumor size and location on survival in upper
      tract urothelial carcinoma after nephroureterectomy".

PMID- 29343918
TI  - Pediatric pelvic fracture urethral distraction defect causing complete
      urethrovaginal avulsion.
AB  - Pelvic fracture with urethral injury in girls is an uncommon entity that is
      usually associated with concomitant vaginal lacerations. Management options vary
      from immediate exploration and urethral anastomosis to delayed urethroplasty. We
      report our experience of managing a 10-year old girl presenting 6 months after a
      pelvic fracture with urethrovaginal injury and a completely obliterated urethral
      meatus managed successfully with a single-stage bladder tube repair.

PMID- 29343919
TI  - Papillary renal cell carcinoma with abscess formation: A report of three cases.
AB  - We report three cases of renal cell carcinoma (RCC) associated with abscess
      formation. Such association has been reported uncommonly in literature. Our cases
      were unique in that final histopathological report was papillary RCC in all of
      the patients.

PMID- 29343920
TI  - Extrarenal retroperitoneal angiomyolipoma with oncocytoma.
AB  - The simultaneous presence of renal angiomyolipoma and oncocytoma is a rare
      occurrence. Extrarenal retroperitoneal angiomyolipoma is an even more rare
      neoplasm, and its simultaneous presence with renal oncocytoma has not been
      documented. We present herein the first case to be reported in English
      literature.

PMID- 29343921
TI  - Ureteropelvic junction obstruction - mimicking an "elephant head" on magnetic
      resonance imaging.
AB  - Ureteropelvic junction obstruction (UPJO) with giant hydronephrosis is relatively
      rare in adults as compared to children. Most of the UPJO reported or seen in
      daily practice have a distinct hydronephrosis with a narrow ureteropelvic
      junction and a collapsed ureter distally. We present images a case of an adult
      female with Left UPJO, which on MRI mimicked an 'elephant head'.

PMID- 29343922
TI  - Periureteral inferior vena caval venous ring presenting as urinary obstruction.
AB  - The embryological development of the inferior vena cava (IVC) is complex, and
      thus the vena cava may undergo a large number of congenital anomalies.
      Periureteric venous ring is a rare developmental anomaly of IVC where the right
      ureter passes through a slit-like opening in a partially duplicated infrarenal
      IVC, resulting in dilatation of upper urinary tract. Split-bolus multidetector
      computed tomography technique is useful in detecting such vascular anomaly
      causing ureteric obstruction as it can clearly show the vascular and ureteric
      phase in a single acquisition.

PMID- 29343923
TI  - Author Reply Re: Goel A. Research training during residency. Indian J Urol
      2017;33:257-8.

PMID- 29343924
TI  - IJU Awards 2017.

PMID- 29343925
TI  - From Editor's Desk.

PMID- 29343926
TI  - Cancer: Prevention and Rehabilitation through Yoga.

PMID- 29343928
TI  - Exploration of Lower Frequency EEG Dynamics and Cortical Alpha Asymmetry in Long
      term Rajyoga Meditators.
AB  - Background: Rajyoga meditation is taught by Prajapita Brahmakumaris World
      Spiritual University (Brahmakumaris) and has been followed by more than one
      million followers across the globe. However, rare studies were conducted on
      physiological aspects of rajyoga meditation using electroencephalography (EEG).
      Band power and cortical asymmetry were not studied with Rajyoga meditators. Aims:
      This study aims to investigate the effect of regular meditation practice on EEG
      brain dynamics in low-frequency bands of long-term Rajyoga meditators. Settings
      and Design: Subjects were matched for age in both groups. Lower frequency EEG
      bands were analyzed in resting and during meditation. Materials and Methods:
      Twenty-one male long-term meditators (LTMs) and same number of controls were
      selected to participate in study as par inclusion criteria. Semi high-density EEG
      was recorded before and during meditation in LTM group and resting in control
      group. The main outcome of the study was spectral power of alpha and theta bands
      and cortical (hemispherical) asymmetry calculated using band power. Statistical
      Analysis: One-way ANOVA was performed to find the significant difference between
      EEG spectral properties of groups. Pearson's Chi-square test was used to find
      difference among demographics data. Results: Results reveal high-band power in
      alpha and theta spectra in meditators. Cortical asymmetry calculated through EEG
      power was also found to be high in frontal as well as parietal channels. However,
      no correlation was seen between the experience of meditation (years, hours)
      practice and EEG indices. Conclusion: Overall findings indicate contribution of
      smaller frequencies (alpha and theta) while maintaining meditative experience.
      This suggests a positive impact of meditation on frontal and parietal areas of
      brain, involved in the processes of regulation of selective and sustained
      attention as well as provide evidence about their involvement in emotion and
      cognitive processing.

PMID- 29343929
TI  - Yoga Offers Cardiovascular Protection in Early Postmenopausal Women.
AB  - Context: Postmenopause, an estrogen deficient state comes with increased
      incidence of cardiovascular diseases (CVDs). Yoga has been described as having a
      beneficial effect on heart rate variability (HRV), a marker for cardiac autonomic
      activity which can assess cardiovascular risk, in various populations. Aim: the
      aim of the study was to study the effect of 3-month long Yoga practice on HRV in
      early postmenopausal women. Settings and Design: A prospective longitudinal study
      of 67 women within 5 years of menopause between 45 and 60 years of age attending
      menopause clinic of Department of Gynaecology, Sucheta Kriplani Hospital
      fulfilling inclusion and exclusion criteria and consenting were enrolled for the
      study. Subjects and Methods: HRV of 37 cases (Yoga group) and 30 controls (non
      Yoga group) was recorded pre and 3-month postintervention. Statistical Analysis
      Used: GraphPad Prism Version 5 software was used. Values are a mean and standard
      error of mean. Statistical significance was set up at P < 0.05. Results: In HRV,
      frequency domain analysis showed a significant fall in low frequency (LF) in
      normalized units (nu) and LF: high frequency (HF) ratio and significant rise in
      HF in nu in the Yoga group (depicting parasympathetic dominance) against a
      significant rise in LF (nu) and LF: HF ratio and significant fall in HF (nu) in
      non-Yoga group (indicating sympathetic dominance). Time domain analysis showed a
      significant decrease in Standard Deviation of NN intervals in Non-Yoga group
      against nonsignificant changes in Yoga group indicating deterioration in
      parasympathetic activity in non-Yoga group. Conclusions: Three-month long Yoga
      practice improved HRV in early postmenopausal women significantly and has the
      potential to attenuate the CVD risk in postmenopausal women.

PMID- 29343927
TI  - Yoga into Cancer Care: A Review of the Evidence-based Research.
AB  - To cope with cancer and its treatment-related side effects and toxicities, people
      are increasingly using complementary and alternative medicine (CAM).
      Consequently, integrative oncology, which combines conventional therapies and
      evidence-based CAM practices, is an emerging discipline in cancer care. The use
      of yoga as a CAM is proving to be beneficial and increasingly gaining popularity.
      An electronic database search (PubMed), through December 15, 2016, revealed 138
      relevant clinical trials (single-armed, nonrandomized, and randomized controlled
      trials) on the use of yoga in cancer patients. A total of 10,660 cancer patients
      from 20 countries were recruited in these studies. Regardless of some
      methodological deficiencies, most of the studies reported that yoga improved the
      physical and psychological symptoms, quality of life, and markers of immunity of
      the patients, providing a strong support for yoga's integration into conventional
      cancer care. This review article presents the published clinical research on the
      prevalence of yoga's use in cancer patients so that oncologists, researchers, and
      the patients are aware of the evidence supporting the use of this relatively safe
      modality in cancer care.

PMID- 29343931
TI  - Effect of Modified Slow Breathing Exercise on Perceived Stress and Basal
      Cardiovascular Parameters.
AB  - Context: Different types of breathing exercises have varied effects on
      cardiovascular parameters and the stress levels in an individual. Aim: The aim of
      this study was to assess the effect of a modified form of isolated alternate
      nostril, slow breathing exercise on perceived stress, and cardiovascular
      parameters in young, male volunteers. Settings and Design: This was a randomized
      control study carried out at Advanced Centre for Yoga Therapy Education and
      Research, Department of Physiology, Jawaharlal Institute of Postgraduate Medical
      Education and Research, Puducherry in 2014. Subjects and Methods: Hundred healthy
      male volunteers were randomized into control group, n = 50 and slow breathing
      group (study), n = 50. Slow breathing exercise training was given to study group
      for 30 min a day, 5 times/week for 12 weeks, under the supervision of certified
      yoga trainers. Perceived Stress Scale (PSS) using Cohen's questionnaire,
      anthropometric parameters such as body mass index (BMI), waist-hip ratio (WHR),
      and cardiovascular parameters such as heart rate (HR), systolic blood pressure
      (SBP), and diastolic blood pressure (DBP) were recorded at baseline and after 12
      weeks. The control group did not receive any intervention. Slow breathing
      exercise training was provided for the study group. During the study period, one
      volunteer opted out of the study group due to personal reasons. Results: HR, SBP,
      DBP, and PSS decreased significantly (P < 0.05) in the study group following 12
      weeks slow breathing exercise training, while no significant change (P > 0.05)
      was observed in BMI and WHR. There was no significant change in the control
      group. Conclusion: Twelve weeks of modified slow breathing exercise reduced
      perceived stress and improved the cardiovascular parameters. The above results
      indicate that our modified slow breathing exercise is effective in reducing
      stress and improving the cardiovascular parameters.

PMID- 29343930
TI  - Yoga-Based Postoperative Cardiac Rehabilitation Program for Improving Quality of
      Life and Stress Levels: Fifth-Year Follow-up through a Randomized Controlled
      Trial.
AB  - Objectives: This study was aimed to assess the efficacy of yoga-based lifestyle
      program (YLSP) in improving quality of life (QOL) and stress levels in patients
      after 5 years of coronary artery bypass graft (CABG). Methodology: Three hundred
      patients posted for elective CABG in Narayana Hrudayalaya Super Speciality
      Hospital, Bengaluru, were randomized into two groups: YLSP and conventional
      lifestyle program (CLSP), and follow-up was done for 5 years. Intervention: In
      YLSP group, all practices of integrative approach of yoga therapy such as yama,
      niyama, asana, pranayama, and meditation were used as an add-on to conventional
      cardiac rehabilitation. The control group (CLSP) continued conventional cardiac
      rehabilitation only. Outcome Measures: World Health Organization (WHO)-QOL BREF
      Questionnaire, Perceived Stress Scale, Positive and Negative Affect Scale
      (PANAS), and Hospital Anxiety and Depression Scale (HADS) were assessed before
      surgery and at the end of the 5th year after CABG. As data were not normally
      distributed, Mann-Whitney U-test was used for between-group comparisons and
      Wilcoxon's signed-rank test was used for within-group comparisons. Results: At
      the end of 5 years, mental health (P = 0.05), perceived stress (P = 0.01), and
      negative affect (NA) (P = 0.05) have shown significant improvements. WHO-QOL BREF
      score has shown improvements in physical health (P = 0.046), environmental health
      (P = 0.04), perceived stress (P = 0.001), and NA (P = 0.02) in YLSP than CLSP.
      Positive affect has significantly improved in CLSP than YLSP. Other domains of
      WHO-QOL-BREF, PANAS, and HADS did not reveal any significant between-group
      differences. Conclusion: Addition of long-term YLSP to conventional cardiac
      rehabilitation brings better improvements in QOL and reduction in stress levels
      at the end of 5 years after CABG.

PMID- 29343932
TI  - Effects of Multimodal Mandala Yoga on Social and Emotional Skills for Youth with
      Autism Spectrum Disorder: An Exploratory Study.
AB  - Context: Youth with autism spectrum disorder (ASD) demonstrates impairment in the
      ability to socially and emotionally relate to others that can limit participation
      in groups, interaction with peers, and building successful life relationships.
      Aims: The aim of this exploratory study was to examine the effects of a novel
      multimodal Mandala yoga program on social and emotional skills for youth with
      ASD. Subjects and Methods: Five males with ASD attended 1 h yoga sessions, twice
      a week for 4 weeks. Multimodal Mandala yoga comprised 26 circular partner/group
      poses, color and tracing sheets, rhythmic chanting, yoga cards, and games.
      Treatment and Research Institute for ASD Social Skills Assessment (TSSA) scores
      were collected before and after the eight yoga sessions. The Modified Facial Mood
      Scale (MFMS) was used to observe mood changes before and after each yoga class.
      Paired sample t-tests were conducted on TSSA and MFMS scores to compare social
      and emotional differences post the 4-week camp. Narrative field notes were
      documented after each of the eight yoga sessions. Results: A significant
      improvement from pre- to post-test was found in overall TSSA (t(4) = -5.744, P =
      0.005) and on respondent to initiation (t(4) = -3.726, P = 0.020), initiating
      interaction (t(4) = -8.5, P = 0.039), and affective understanding and perspective
      taking subscales (t(4) = -5.171 P = 0.007). Youth's MFMS scores increased from
      80% to 100% at the end of eight yoga sessions demonstrating a pleasant or
      positive mood. Thematic analysis of the narrative notes identified three key
      factors associated with the yoga experience: (a) enhanced mood and emotional
      expression, (b) increased empathy toward others, and (c) improved teamwork
      skills. Conclusion: This multimodal Mandala yoga training has implication for
      developing positive social and emotional skills for youth with ASD.

PMID- 29343933
TI  - Effects of Maharishi Yoga Asanas on Mood States, Happiness, and Experiences
      during Meditation.
AB  - Context/Background: Many studies showed positive effects of Yoga Asanas. There is
      no study on Maharishi Yoga Asanas yet. This research replicated and expanded
      observed improvements on the profile of mood states (POMS) as a result of 2-week
      Maharishi Yoga Asanas course. Thirteen college students taking part in a 4-week
      course on Maharishi Yoga Asanas were matched with 13 students taking other
      courses at the university. Aims and Objective: The main objective of the study
      was to assess the effects of Maharishi Yoga Asanas on mood states, degree of
      happiness, and experiences in Transcendental Meditation (TM) practice. Methods:
      All students were given two psychological tests and additional question before
      and after their 4-week course: POMS, Meditation Depth Questionnaire, and question
      about the degree of happiness. Results: Repeated measure MANOVA showed the 4-week
      Maharishi Yoga Asanas course resulted in significant increase in happiness during
      the day and significant improvements in (1) sense of personal self, (2)
      transpersonal qualities, and (3) transpersonal self during their TM practice.
      Conclusion: This research shows that Maharishi Yoga Asanas affect more than body
      and mind. Rather they influence much deeper levels of one's subjectivity
      including one's transpersonal self.

PMID- 29343934
TI  - A Comparative Study on the Effects of Vintage Nonpharmacological Techniques in
      Reducing Myopia (Bates eye exercise therapy vs. Trataka Yoga Kriya).
AB  - Background: Human eye captures light rays as they come and fall on the retina and
      convert them into an image. However, in myopia, light rays fall in front of
      retina, causing blurring of image. Correction of this is generally done using
      correcting devices such as corrective glasses and contact lenses. Existence of
      some alternative therapies is also noticed in literature. Aim: To compare the
      effects of Bates eye exercises and Trataka Yoga Kriya on myopia. Materials and
      Methodology: Ethical clearance was obtained from the institution, and informed
      consent was taken from participants. In this randomized comparative study, 24
      participants (48 eyes) were taken based on inclusion and exclusion criteria and
      were randomly divided into two groups: Group A and Group B, where Bates eye
      exercise therapy and Trataka Yoga Kriya were given, respectively, for 8 weeks.
      Participants were assessed for their refractive errors and visual acuity pre- and
      post-intervention. Results: Data were analyzed by SPSS version 20. Results
      obtained revealed that both Bates exercises and Trataka Yoga Kriya were not
      significantly effective in reducing refractive errors and in improving visual
      acuity (P value of refractive error in right eye: 0.4250; left eye: 0.4596; P
      value of visual acuity in right eye: 0.5691; left eye: 0.8952). Conclusion: This
      study concludes that nonpharmacological approaches such as eye exercises and
      Trataka Yoga Kriya are not significant on myopia.

PMID- 29343935
TI  - Effectiveness of Mindfulness-based Cognitive Therapy in Patients with Bipolar
      Affective Disorder: A Case Series.
AB  - The present investigation was undertaken to examine the effects of mindfulness
      based cognitive therapy (MBCT) on interepisodic symptoms, emotional regulation,
      and quality of life in patients with bipolar affective disorder (BPAD) in
      remission. The sample for the study comprised a total of five patients with the
      diagnosis of BPAD in partial or complete remission. Each patient was screened to
      fit the inclusion and exclusion criteria and later assessed on the Beck
      Depressive Inventory I, Beck Anxiety Inventory, Difficulties in Emotion
      Regulation Scale, Acceptance and Action Questionnaire-II, and The World Health
      Organization Quality of Life Assessment-BREF. Following preassessments, patients
      underwent 8-10 weeks of MBCT. A single case design with pre- and post
      intervention assessment was adopted to evaluate the changes. Improvement was
      observed in all five cases on the outcome variables. The details of the results
      are discussed in the context of the available literature. Implications,
      limitations, and ideas for future investigations are also discussed.

PMID- 29343936
TI  - The Conclusions Are Unsupported by the Data, Are Based on Invalid Analyses, Are
      Incorrect, and Should be Corrected: Letter Regarding "Sleep Quality and Body
      Composition Variations in Obese Male Adults after 14 weeks of Yoga Intervention:
      A Randomized Controlled Trial".

PMID- 29343937
TI  - Response to Comment on "Sleep Quality and Body Composition Variations in Obese
      Male Adults after 14 Weeks of Yoga Intervention: A Randomized Controlled Trial"
      by Rshikesan et al., 2017.

PMID- 29343938
TI  - CINdex: A Bioconductor Package for Analysis of Chromosome Instability in DNA Copy
      Number Data.
AB  - The CINdex Bioconductor package addresses an important area of high-throughput
      genomic analysis. It calculates the chromosome instability (CIN) index, a novel
      measurement that quantitatively characterizes genome-wide copy number alterations
      (CNAs) as a measure of CIN. The advantage of this package is an ability to
      compare CIN index values between several groups for patients (case and control
      groups), which is a typical use case in translational research. The
      differentially changed cytobands or chromosomes can then be linked to genes
      located in the affected genomic regions, as well as pathways. This enables in
      depth systems biology-based network analysis and assessment of the impact of CNA
      on various biological processes or clinical outcomes. This package was
      successfully applied to analysis of DNA copy number data in colorectal cancer as
      a part of multi-omics integrative study as well as for analysis of several other
      cancer types. The source code, along with an end-to-end tutorial, and example
      data are freely available in Bioconductor at
      http://bioconductor.org/packages/CINdex/.

PMID- 29343939
TI  - Kinetics of Procalcitonin in Pediatric Patients on Extracorporeal Membrane
      Oxygenation.
AB  - Objectives: To assess the kinetics of procalcitonin (PCT) and C-reactive protein
      (CRP) in pediatric patients who required extracorporeal membrane oxygenation
      (ECMO) and to analyze its relationship with morbidity and mortality. Patients and
      methods: Prospective observational study including pediatric patients who
      required ECMO. Both PCT and CRP were sequentially drawn before ECMO (P0) and
      until 72 hours after ECMO. Results: A total of 40 patients were recruited. Two
      cohorts were established based on the value of the P0 PCT (>10 ng/mL). Comparing
      the kinetics of PCT and CRP in these cohorts, the described curves were the
      expected for each clinical situation. The cutoff for P0 PCT to predict multiple
      organ dysfunction syndrome was 2.55 ng/mL (sensibility 83%, specificity 100%).
      Both PCT and CRP did not predict risk of neurologic sequelae or mortality in any
      group. Conclusions: Procalcitonin does not seem to be modified by ECMO and could
      be a good biomarker of evolution.

PMID- 29343940
TI  - Prescreening whole exome sequencing results from patients with retinal
      degeneration for variants in genes associated with retinal degeneration.
AB  - Background: Accurate clinical diagnosis and prognosis of retinal degeneration can
      be aided by the identification of the disease-causing genetic variant. It can
      confirm the clinical diagnosis as well as inform the clinician of the risk for
      potential involvement of other organs such as kidneys. It also aids in genetic
      counseling for affected individuals who want to have a child. Finally, knowledge
      of disease-causing variants informs laboratory investigators involved in
      translational research. With the advent of next-generation sequencing,
      identifying pathogenic mutations is becoming easier, especially the
      identification of novel pathogenic variants. Methods: We used whole exome
      sequencing on a cohort of 69 patients with various forms of retinal degeneration
      and in whom screens for previously identified disease-causing variants had been
      inconclusive. All potential pathogenic variants were verified by Sanger
      sequencing and, when possible, segregation analysis of immediate relatives.
      Potential variants were identified by using a semi-masked approach in which rare
      variants in candidate genes were identified without knowledge of the clinical
      diagnosis (beyond "retinal degeneration") or inheritance pattern. After the
      initial list of genes was prioritized, genetic diagnosis and inheritance pattern
      were taken into account. Results: We identified the likely pathogenic variants in
      64% of the subjects. Seven percent had a single heterozygous mutation identified
      that would cause recessive disease and 13% had no obviously pathogenic variants
      and no family members available to perform segregation analysis. Eleven subjects
      are good candidates for novel gene discovery. Two de novo mutations were
      identified that resulted in dominant retinal degeneration. Conclusion: Whole
      exome sequencing allows for thorough genetic analysis of candidate genes as well
      as novel gene discovery. It allows for an unbiased analysis of genetic variants
      to reduce the chance that the pathogenic mutation will be missed due to
      incomplete or inaccurate family history or analysis at the early stage of a
      syndromic form of retinal degeneration.

PMID- 29343941
TI  - Clinical features of hypophosphatemic osteomalacia induced by long-term low-dose
      adefovir dipivoxil.
AB  - Objective: To investigate the predictors of hypophosphatemic osteomalacia induced
      by adefovir dipivoxil (ADV) and to monitor for early detection. Patients and
      methods: Hospitalized patients who were diagnosed with ADV-related hypo
      phosphatemic osteomalacia were recruited and retrospectively analyzed in our
      hospital from January 2012 to December 2016. A telephone interview was conducted
      at 1, 3, 6, 9, 12, and 24 months after cessation of ADV. Results: In the 8
      patients enrolled in the study, the hypophosphatemic osteomalacia symptoms
      developed at an average of 5.14 (4-7) years since ADV treatment (10 mg/d). The
      average alkaline phosphatase (ALP) level was 279.50 (137-548) U/L, which was
      significantly higher than the normal level (45-125 U/L). The serum phosphorus
      level was an average of 0.59 (0.43-0.69) mmol/L, which was lower than the normal
      range (2.06-2.60 mmol/L). Serum calcium levels of the enrolled patients remained
      within normal limits. Reduced estimated glomerular filtration rate (eGFR <29
      mL/min/1.73 m2) was seen in 4 cases. The clinical manifestations were mainly
      progressive systemic bone and joint pain, frequent fractures, trouble in walking,
      height reduction (4-6 cm), and so on. After cessation of ADV, symptoms like bone
      pain resolved gradually. Serum phosphorus level restored to normal in 4.5 months
      after the withdrawal of ADV. However, in 4 patients, renal function failed to
      return to normal in 24 months. Conclusion: More attention should be paid to the
      duration of ADV treatment. The level of serum phosphorus and ALP, as well as
      renal function, should be monitored for early detection of potential adverse drug
      reactions.

PMID- 29343942
TI  - Portulaca oleracea L. alleviates liver injury in streptozotocin-induced diabetic
      mice.
AB  - Purslane is a widespread succulent herb that exhibits various pharmacological
      effects. The purpose of this study was to evaluate the protective effect of
      Portulaca oleracea L. (purslane) on streptozotocin-induced diabetes in mice. Oral
      glucose-tolerance tests were carried out to assess blood glucose levels and body
      weight and food intake were recorded. The biochemical parameters anti-aspartate
      aminotransferase, alanine aminotransferase, insulin, triglycerides, total
      cholesterol, IL-6, IL-1beta, and TNFalpha were also measured. The pathological
      condition of liver tissues were examined by hematoxylin-eosin staining. Rho,
      ROCK1, ROCK2, NFkappaBp65, p-NFkappaBp65, IkappaBalpha, and p-IkappaBalpha
      expression in liver tissue were analyzed by Western blot. Purslane increased body
      weight and decreased food intake. Purslane also significantly reduced
      concentrations of glucose, anti-aspartate aminotransferase, alanine
      aminotransferase, triglycerides, total cholesterol, IL-6, IL-1beta, and TNFalpha
      in serum. Serum insulin was elevated with purslane treatment. In addition,
      pathologic liver changes in diabetic mice were also alleviated by purslane.
      Obtained data revealed that purslane restored the levels of Rho-NFkappaB
      signaling-related proteins in comparison with those of diabetic mice. Above all,
      it can be assumed that purslane might play a positive role in regulating
      streptozotocin-induced liver injury through suppressing the Rho-NFkappaB pathway.

PMID- 29343943
TI  - The oral bioavailability, excretion and cytochrome P450 inhibition properties of
      epiberberine: an in vivo and in vitro evaluation.
AB  - Epiberberine (EPI) is a novel and potentially effective therapeutic and
      preventive agent for diabetes and cardiovascular disease. To evaluate its
      potential value for drug development, a specific, sensitive and robust high
      performance liquid chromatography-tandem mass spectrometry assay for the
      determination of EPI in rat biological samples was established. This assay was
      used to study the pharmacokinetics, bioavailability and excretion of EPI in rats
      after oral administration. In addition, a cocktail method was used to compare the
      inhibition characteristics of EPI on cytochrome P450 (CYP450) isoforms in human
      liver microsomes (HLMs) and rat liver microsomes (RLMs). The results demonstrated
      that EPI was rapidly absorbed and metabolized after oral administration (10, 54
      or 81 mg/kg) in rats, with Tmax of 0.37-0.42 h and T1/2 of 0.49-2.73 h. The Cmax
      and area under the curve values for EPI increased proportionally with the dose,
      and the oral absolute bioavailability was 14.46%. EPI was excreted mainly in bile
      and feces, and after its oral administration to rats, EPI was eliminated
      predominantly by the kidneys. A comparison of the current half-maximal inhibitory
      concentration and Ki values revealed that EPI demonstrated an obvious inhibitory
      effect on CYP2C9 and CYP2D6. Furthermore, its effect was stronger in HLM than in
      RLM, more likely to be a result of noncompetitive inhibition.

PMID- 29343944
TI  - Quantitative assessment of the effects of chitosan intervention on blood pressure
      control.
AB  - Background: Chitosan is a popular dietary fiber often used to reduce dietary fat
      absorption to control weight and blood lipids. However, its effects on blood
      pressure (BP) have not been fully elucidated. We evaluated the effects of
      chitosan administration on systolic blood pressure (SBP) and diastolic blood
      pressure (DBP) through a pooled analysis of available randomized controlled
      trials (RCTs). Materials and methods: Electronic searches were conducted in
      Medline, Cochrane Library, Scopus, and EMBASE to identify relevant human placebo
      control RCTs. Trials that reported BP changes from baseline to study endpoint in
      patients receiving treatment of chitosan were included for analysis. Weighted
      mean difference (WMD) and 95% CIs were pooled using fixed-effects or random
      effects models. Statistical heterogeneity, prespecified subgroup, publication
      bias, sensitivity analysis, and meta-regression assessments were also tested.
      Results: Six hundred and seventeen participants from eight trials with 10 arms
      were included. Overall, chitosan administration did not significantly lower SBP
      (WMD: -1.41 mmHg, 95% CI: -3.29 to 0.47; P=0.14) and DBP (WMD: -0.61 mmHg, 95%
      CI: -1.75 to 0.52; P=0.29). However, our subgroup analyses indicated that
      chitosan consumption significantly reduced DBP in shorter-term (<12 weeks) and
      higher-dose (>2.4 g/day) arms. Funnel plots or Egger's tests analysis (P=0.36 and
      0.43 for SBP and DBP, respectively) demonstrated that there was no significant
      publication bias in this study. Conclusion: This meta-analysis indicates that
      chitosan consumption significantly decreases DBP at higher dosage and in shorter
      term interventions, while chitosan has no significant effects on SBP. However,
      these results should be interpreted cautiously because of the limited eligible
      RCTs included in this meta-analysis; further large-scale, well-designed RCTs on
      this topic are urgently needed.

PMID- 29343945
TI  - The impact of pharmaceutical interventions on the rational use of proton pump
      inhibitors in a Chinese hospital.
AB  - Background: The prescriptions of proton pump inhibitors (PPIs) have raised
      concern due to both huge increase in medical expenditure and the possible long
      term adverse events caused by them; therefore, an approach to taper off the
      irrational use of PPIs by patients is clinically warranted. The aim of this study
      was to evaluate the impact of pharmaceutical interventions on the rational use of
      PPIs. Patients and methods: A single-center, pre- to post-intervention study
      (pharmaceutical interventions group and control group) was performed in a Chinese
      hospital. Pharmaceutical interventions were performed in the post-intervention
      group, including educative group activities, real-time monitoring of clinical
      records and making recommendations to doctors on PPI prescriptions based on the
      criteria set at the beginning of the study. The number of patients with rational
      indication, the accuracy rate of administration route, the duration of therapy
      and the changes in total PPI costs, mean PPI costs, mean total drug costs and
      mean hospitalization costs were the main outcome measures. Results: A total of
      285 patients were included in the study. After 6 months of interventions,
      significant improvements in the number of patients with rational indication were
      found (96.5% in the pharmaceutical interventions group vs 71.8% in the control
      group, P<0.01). The accuracy rate of administration route was increased (99.3% vs
      73.2%, P<0.05), while the duration of therapy was decreased (7.9+/-0.5 vs 14.3+/
      0.8, P<0.01). Pharmaceutical interventions led to significant reductions in mean
      PPIs costs, mean total drug costs and mean hospitalization costs (P<0.001).
      Conclusion: This study provides important evidence on the beneficial effect of
      pharmaceutical interventions on enhancing the rational use of PPIs and
      substantial cost saving by increasing the number of patients with rational
      indication and reducing the risk for long-term adverse events.

PMID- 29343946
TI  - A new pen device for injection of recombinant human growth hormone: a
      convenience, functionality and usability evaluation study.
AB  - Purpose: Adherence to recombinant human growth hormone (r-hGH) is critical to
      growth and other outcomes in patients with growth disorders, but the requirement
      for daily injections means that ease of use is an important factor. This study
      assessed the perceived ease of use and functionality of the prototype of a
      reusable pen injector (pen device) for r-hGH that incorporates several advanced
      features. Participants and methods: Semi-structured 60-minute qualitative
      interviews were conducted in 5 countries with 57 health care professionals (HCPs)
      and 30 patients with GH deficiency/caregivers administering r-hGH to patients,
      including children. HCPs had to be responsible for training in the use of r-hGH
      pen devices and to see >=4 r-hGH patients/caregivers per month.
      Patients/caregivers had to have experience with r-hGH administration for at least
      6 months. Results: Thirty-seven (65%) of HCPs described the pen device as
      "simple" or "easy" to use. The aluminum body was generally perceived as
      attractive, high quality and comfortable to hold and operate. The ease of
      preparation and use made it suitable for both children and adults. The ability to
      dial back the r-hGH dose, if entered incorrectly, was mentioned as a major
      benefit, because other devices need several user steps to reset.
      Patients/caregivers felt the pen device was easy to use and the injection
      feedback features reassured them that the full dose had been given. Overall, 40
      (70%) HCPs and 16 (52%) patients/caregivers were likely to recommend or request
      the pen device. Moreover, patients/caregivers rated the pen device higher than
      their current reusable pens and almost equal to the leading disposable device for
      ease of learning, preparation, administration and ease of use. Conclusion: The
      prototype pen device successfully met its design objectives and was very well
      accepted by HCPs and patients/caregivers for its ease of use, appearance and
      functionality.

PMID- 29343947
TI  - Patient preferences for important attributes of bipolar depression treatments: a
      discrete choice experiment.
AB  - Purpose: The purpose of this study was to assess patient preferences regarding
      pharmacological treatment attributes for bipolar depression using a discrete
      choice experiment (DCE). Methods: Adult members of an Internet survey panel with
      a self-reported diagnosis of bipolar depression were invited via e-mail to
      participate in a web-based DCE survey. Participants were asked to choose between
      hypothetical medication alternatives defined by attributes and levels that were
      varied systematically. The six treatment attributes included in the DCE were time
      to improvement, risk of becoming manic, weight gain, risk of sedation, increased
      blood sugar, and increased cholesterol. Attributes were supported by literature
      review, expert input, and results of focus groups with patients. Sawtooth CBC
      System for Choice-Based Conjoint Analysis was used to estimate the part-worth
      utilities for the DCE analyses. Results: The analytical sample included 185
      participants (50.8% females) from a total of 200 participants. The DCE analyses
      found weight gain to be the most important treatment attribute (relative
      importance =49.6%), followed by risk of sedation (20.2%), risk of mania (13.0%),
      increased blood sugar (8.3%), increased cholesterol (5.2%), and time to
      improvement (3.7%). Conclusion: Results from this DCE suggest that adults with
      bipolar depression considered risks of weight gain and sedation associated with
      pharmacotherapy as the most important attributes for the treatment of bipolar
      depression. Incorporating patient preferences in the treatment decision-making
      process may potentially have an impact on treatment adherence and satisfaction
      and, ultimately, patient outcomes.

PMID- 29343948
TI  - Types and delivery of emotional support to promote linkage and engagement in HIV
      care.
AB  - Purpose: Despite recommendations for early entry into human immunodeficiency
      virus (HIV) care, many people diagnosed with HIV delay seeking care. Multiple
      types of social support (ie, cognitive, emotional, and tangible) are often needed
      for someone to transition into HIV care, but a lack of emotional support at
      diagnosis may be the reason why some people fail to stay engaged in care. Thus,
      the purpose of this study was to identify how people living with HIV
      conceptualized emotional support needs and delivery at diagnosis. Method: We
      conducted a secondary analysis of qualitative data from 27 people living with
      HIV, many of whom delayed entry into HIV care. Results: Participants described
      their experiences seeking care after an HIV diagnosis and identified components
      of emotional support that aided entry into care - identification, connection, and
      navigational presence. Many participants stated that these types of support were
      ideally delivered by peers with HIV. Conclusion: In clinical practice, providers
      often use an HIV diagnosis as an opportunity to educate patients about HIV
      prevention and access to services. However, this type of social support may not
      facilitate engagement in care if emotional support needs are not met.

PMID- 29343949
TI  - Clinical observations on the use of new anti-VEGF drug, conbercept, in age
      related macular degeneration therapy: a meta-analysis.
AB  - Purpose: Conbercept is a new anti-vascular endothelial growth factor (VEGF) drug
      approved for the treatment of age-related macular degeneration (AMD). Although
      this novel drug has been widely used in clinic, unlike other anti-VEGF drugs,
      validation and consensus on its method of clinical application and clinical
      safety have not yet been achieved. Methods: Relevant literature was searched on
      PubMed, Web of Science, China National Knowledge Internet, and Wanfang Data.
      Stata 12.0 was used for data analysis. Random- and fixed-effect models were
      employed to evaluate heterogeneity. Best-corrected visual acuity (BCVA) and
      central retinal thickness (CRT) were utilized to measure the improvement of AMD
      patients. Results: In this study, we analyzed conbercept administration and
      compared its application with other control clinical methods for AMD treatment.
      Ranibizumab, triamcinolone, and traditional transpupillary thermotherapy (TTT)
      were administered in the control group. No differences were found in the BCVA and
      CRT improvement between the groups treated with conbercept and ranibizumab.
      However, the conbercept group had a lower serum VEGF level. After 3 months of
      treatment, conbercept led to a more significant BCVA and CRT improvement than
      triamcinolone. A more considerable BCVA improvement was observed in the group
      treated with conbercept than in the group treated with TTT. Moreover, even 6
      months after the treatment, the effect of conbercept on CRT improvement was still
      more pronounced than that of TTT. Conclusion: In AMD patients, conbercept exerts
      considerably more positive effects on the long-term BCVA and CRT improvement than
      triamcinolone and TTT. The serum VEGF level in the conbercept group was lower
      than that in the ranibizumab group.

PMID- 29343950
TI  - Examining 30-day COPD readmissions through the emergency department.
AB  - Background: Thirty-day readmission in COPD is common and costly, but potentially
      preventable. The emergency department (ED) may be a setting for COPD readmission
      reduction efforts. Objective: To better understand COPD readmission through the
      ED, ascertain factors associated with 30-day readmission through the ED, and
      identify subgroups of patients with COPD for readmission reduction interventions.
      Patients and methods: A retrospective cohort study was conducted from January
      2009 to September 2015 in patients with COPD of age >=18 years. Electronic health
      record data were abstracted for information available to admitting providers in
      the ED. The primary outcome was readmission through the ED within 30 days of
      discharge from an index admission for COPD. Logistic regression was used to
      examine the relationship between potential risk factors and 30-day readmission.
      Results: The study involved 1,574 patients who presented to the ED within 30 days
      on an index admission for COPD. Of these, 82.2% were readmitted through the ED.
      Charlson score (odds ratio [OR]: 3.6; 95% CI: 2.9-4.4), a chief complaint of
      breathing difficulty (OR: 1.6; 95% CI: 1.1-2.6), outpatient utilization of
      albuterol (OR: 4.1; 95% CI: 2.6-6.4), fluticasone/salmeterol (OR: 2.3; 95% CI:
      1.3-4.2), inhaled steroids (OR: 3.8; 95% CI: 1.3-10.7), and tiotropium (OR: 1.8;
      95% CI: 1.0-3.2), as well as arterial blood gas (OR: 4.4; 95% CI: 1.3-15.1) and B
      type natriuretic peptide (OR: 2.2; 95% CI: 1.4-3.5) testing in the ED were
      associated with readmission (c-statistic =0.936). Seventeen-point-eight percent
      of patients with COPD presented to the ED and were discharged home; 56% presented
      with a complaint other than breathing difficulty; and 16% of those readmitted for
      breathing difficulty had a length of stay <48 hours. Conclusion: Intensive
      outpatient monitoring, evaluation, and follow-up after discharge are needed to
      help prevent re-presentation to the ED, as practically all patients with COPD who
      represent to the ED within 30 days are readmitted to the hospital and for a
      variety of clinical complaints. Among those patients with COPD who present with
      breathing difficulty, improved decision support algorithms and alternative
      management strategies are needed to identify and intervene on the subgroup of
      patients who require <48-hour length of stay.

PMID- 29343951
TI  - Risk factors predict frequent hospitalization in patients with acute exacerbation
      of COPD.
AB  - Purpose: COPD is a heterogeneous disease, and the available prognostic indexes
      are therefore limited. This study aimed to identify the factors associated with
      acute exacerbation leading to hospitalization. Patients and methods: This was a
      retrospective study of consecutive patients with COPD (meeting the Global
      Initiative for Chronic Obstructive Lung Disease [GOLD] diagnostic criteria)
      hospitalized at the Ninth Hospital of Xi'an Affiliated Hospital of Xi'an Jiaotong
      University between October 2014 and September 2016. During follow-up after first
      hospitalization, the patients who had been rehospitalized within 1 year for acute
      exacerbation were grouped into the frequent exacerbation (FE) group, while the
      others were grouped into the infrequent exacerbation (IE) group. The baseline
      demographic, clinical, laboratory, pulmonary function, and imaging data were
      compared between the two groups. Results: Compared with the IE group, the FE
      group had lower forced expiratory volume in 1 second (FEV1)/forced vital capacity
      (FVC) (P=0.005), FEV1%pred (P=0.002), maximal mid-expiratory flow (MMEF25
      75%pred) (P=0.003), and ratio of carbon monoxide diffusion capacity to alveolar
      ventilation (DLCO/VA) (P=0.03) and higher resonant frequency (Fres; P=0.04).
      According to generations of bronchi, the percentage of the wall area (%WA) of
      lobes was found to be higher in the FE group. Emphysema index (EI), mean
      emphysema density (MED)whole and MEDleft lung in the FE group were significantly
      worse than in the IE group (P<0.05). Using logistic regression, exacerbation
      hospitalizations in the past year (odds ratio [OR] 14.4, 95% CI 6.1-34.0,
      P<0.001) and EI >10% (OR 2.9, 95% CI 1.2-7.1, P=0.02) were independently
      associated with frequent acute exacerbation of COPD (AECOPD) hospitalization.
      Conclusion: Exacerbation hospitalizations in the past year and imaging features
      of emphysema (EI) were independently associated with FE hospitalization.

PMID- 29343952
TI  - Understanding of COPD among final-year medical students.
AB  - Objective: Several previous studies have shown a suboptimal level of
      understanding of COPD among different population groups. Students in their final
      year of Medicine constitute a population that has yet to be explored. The
      evaluation of their understanding provides an opportunity to establish strategies
      to improve teaching processes. The objective of the present study is to determine
      the current level of understanding of COPD among said population. Methods: A
      cross-sectional observational study was done using digital surveys given to
      medical students in their final year at the Universidad de Sevilla. Those
      surveyed were asked about demographic data, smoking habits as well as the
      clinical manifestation, diagnosis and treatment of COPD. Results: Of the 338
      students contacted, responses were collected from 211 of them (62.4%). Only 25.2%
      had an accurate idea about the concept of the disease. The study found that 24.0%
      of students were familiar with the three main symptoms of COPD. Tobacco use was
      not considered a main risk factor for COPD by 1.5% of students. Of those
      surveyed, 22.8% did not know how to spirometrically diagnose COPD. Inhaled
      corticosteroids were believed to be part of the main treatment for this disease
      among 51.0% of the students. Results show that 36.4% of respondents believed that
      home oxygen therapy does not help COPD patients live longer. Only 15.0%
      considered the Body-mass index, airflow Obstruction, Dyspnea, and Exercise (BODE)
      index to be an important parameter for measuring the severity of COPD. Giving up
      smoking was not believed to prevent worsening COPD among 3.4% of students
      surveyed. Almost half of students (47.1%) did not recommend that those suffering
      from COPD undertake exercise. Conclusion: The moderate level of understanding
      among the population of medical students in their final year shows some strengths
      and some shortcomings. Teaching intervention is required to reinforce solid
      knowledge among this population.

PMID- 29343953
TI  - Impact of acute exacerbations on platelet reactivity in chronic obstructive
      pulmonary disease patients.
AB  - Background: A higher risk of atherothrombotic cardiovascular events, which are
      platelet-driven processes, has been described during acute exacerbations of
      chronic obstructive pulmonary disease (AECOPD). However, the relevance of
      platelet reactivity during AECOPD and whether this is affected by antiplatelet
      agents are not fully elucidated to date. This study aimed to evaluate whether
      platelet reactivity is augmented during an exacerbation in COPD patients with and
      without antiplatelet therapy and its association with systemic inflammatory
      parameters. Materials and methods: Prospective, observational, ex vivo
      investigation was conducted in consecutive patients suffering an exacerbation of
      COPD. Platelet reactivity was assessed during AECOPD and at stable state.
      Platelet function assays included: 1) vasodilator-stimulated phosphoprotein assay
      expressed as P2Y12 reactivity index (PRI), 2) multiple electrode aggregometry and
      3) optical aggregometry. Systemic inflammatory parameters such as leukocyte
      count, interleukin-6 and fibrinogen were also assessed. Results: Higher platelet
      reactivity was observed during AECOPD compared to stability measured by
      vasodilator-stimulated phosphoprotein (PRI: 75.2%+/-1.9% vs 68.8%+/-2.4%,
      p=0.001). This augmented platelet aggregability was also observed in the subset
      of patients on antiplatelet therapy (PRI: 72.8%+/-3.1% vs 61.7%+/-7.5%, p=0.071).
      Consistent findings were observed with all other platelet function tests.
      Patients with greater enhancement of inflammatory markers during AECOPD were more
      likely to present a higher increase in platelet reactivity. Conclusion: Platelet
      reactivity is increased during AECOPD, which may contribute to the augmented
      cardiovascular risk of these patients. Additionally, the increase in platelet
      reactivity might be associated with an increment in inflammatory markers during
      exacerbations.

PMID- 29343954
TI  - Exposure to environmental tobacco smoke from husband more strongly impacts on the
      airway obstruction of nonsmoking women.
AB  - Background: The impact of airway obstruction of nonsmoking women caused by their
      husband's smoking is unclear, despite the association between environmental
      tobacco smoke (ETS) exposure at home and obstructive pulmonary diseases among
      nonsmoking women. The aim of this study was to provide evidence that ETS exposure
      from the husband at home has a more significant influence on the airway
      obstruction of nonsmoking women than other housemates. Participants and methods:
      Nonsmoking women aged 40 years or older were recruited from the health checkup
      during May 2015-December 2016, Japan. They answered structured questionnaires,
      including ETS exposure from their husbands and other housemates (parents,
      siblings and dependants), and performed spirometry. We categorized the women with
      any history of ETS exposure from housemates into three groups (A = husband, B =
      others and C = both of husband and others) and defined the control group as those
      with no ETS exposure from housemates. Results: A total of 811 nonsmoking women
      completed questionnaires and spirometry. The proportion of nonsmoking women who
      had airway obstruction (forced expiratory volume in 1 second [FEV1]/forced vital
      capacity [FVC] <70%) among Group A (7.5%) was significantly higher than those in
      the control group (1.1%, p<0.01) and Group B (0.8%, p<0.01). The proportion of
      airway obstruction in Group C (6.4%) was also higher than that in the control
      group (p<0.05) and Group B (p<0.05). ETS exposure from husband (odds ratio [OR],
      3.53; 95% confidence interval [CI], 1.48-8.42) remained strongly associated with
      airway obstruction after multiple logistic regression analysis, adjusting for
      age, housemate's smoking habits, family history and ETS exposure in childhood and
      at work. Conclusion: Nonsmoking women who were exposed to ETS from their husband
      had the lowest FEV1/FVC, and a higher proportion of them had airway obstruction
      when compared to nonsmoking women who experienced ETS from housemates other than
      their husbands. The findings suggest that tobacco control in husbands is the most
      important measure to prevent airway obstruction of nonsmoking women at home.

PMID- 29343955
TI  - Lysyl oxidase activates cancer stromal cells and promotes gastric cancer
      progression: quantum dot-based identification of biomarkers in cancer stromal
      cells.
AB  - Purpose: Semiconductor quantum dots (QDs) are a promising alternative to organic
      fluorescent dyes for multiplexed molecular imaging of cancer stroma, which have
      great advantages in holistically analyzing the complex interactions among cancer
      stromal components in situ. Patients and methods: A QD probe-based multiplexed
      spectral molecular imaging method was established for simultaneous imaging. Three
      tissue microarrays (TMAs) including 184 gastric cancer (GC) tissues were
      constructed for the study. Multispectral analyses were performed for quantifying
      stromal biomarkers, such as lysyl oxidase (LOX). The stromal status including
      infiltrating of immune cells (high density of macrophages), angiogenesis (high
      density of microvessel density [MVD], low neovessel maturation) and extracellular
      matrix (ECM) remodeling (low density of type IV collagen, intense expression of
      matrix metalloproteinase 9 [MMP-9]) was evaluated. Results: This study compared
      the imaging features of the QD probe-based single molecular imaging method,
      immunohistochemistry, and organic dye-based immunofluorescent methods, and showed
      the advantages of the QD probe-based multiple molecular imaging method for
      simultaneously visualizing complex components of cancer stroma. The risk of
      macrophages in high density, high MVD, low neomicrovessel maturation, MMP-9
      expression and low type IV collagen was significantly increased for the
      expression of LOX. With the advantages of the established QD probe-based
      multiplexed molecular imaging method, the spatial relationship between LOX and
      stromal essential events could be simultaneously evaluated histologically.
      Stromal activation was defined and then evaluated. Survival analysis showed that
      the stromal activation was correlated with overall survival and disease-free
      survival (P<0.001 for all). The expression of LOX was significantly increased in
      the intense activation subgroup (P<0.001). Conclusion: Quantifying assessment of
      the stroma indicates that the LOX may be a stromal marker for GC and stromal
      activation, which is not only responsible for the ECM remodeling morphologically,
      but also for the formation of invasive properties and recurrence. These results
      support the possibility to integrate morphological and molecular biomarker
      information for cancer research by the biomedical application of QDs.

PMID- 29343956
TI  - Essential oil-loaded lipid nanoparticles for wound healing.
AB  - Chronic wounds and severe burns are diseases responsible for severe morbidity and
      even death. Wound repair is a crucial process and tissue regeneration enhancement
      and infection prevention are key factors to minimize pain, discomfort, and scar
      formation. The aim of this work was the development of lipid nanoparticles (solid
      lipid nanoparticles and nanostructured lipid carriers [NLC]), to be loaded with
      eucalyptus or rosemary essential oils and to be used, as medical devices, to
      enhance healing of skin wounds. Lipid nanoparticles were based on natural lipids:
      cocoa butter, as solid lipid, and olive oil or sesame oil, as liquid lipids.
      Lecithin was chosen as surfactant to stabilize nanoparticles and to prevent their
      aggregation. The systems were prepared by high shear homogenization followed by
      ultrasound application. Nanoparticles were characterized for physical-chemical
      properties, bioadhesion, cytocompatibility, in vitro proliferation enhancement,
      and wound healing properties toward normal human dermal fibroblasts.
      Antimicrobial activity of nanoparticles was evaluated against two reference
      microbial strains, one of Staphylococcus aureus, the other of Streptococcus
      pyogenes. Finally, the capability of nanoparticles to promote wound healing in
      vivo was evaluated on a rat burn model. NLC based on olive oil and loaded with
      eucalyptus oil showed appropriate physical-chemical properties, good bioadhesion,
      cytocompatibility, in vitro proliferation enhancement, and wound healing
      properties toward fibroblasts, associated to antimicrobial properties. Moreover,
      the in vivo results evidenced the capability of these NLC to enhance the healing
      process. Olive oil, which is characterized by a high content of oleic acid,
      proved to exert a synergic effect with eucalyptus oil with respect to
      antimicrobial activity and wound repair promotion.

PMID- 29343957
TI  - Codelivery of doxorubicin and MDR1-siRNA by mesoporous silica nanoparticles
      polymerpolyethylenimine to improve oral squamous carcinoma treatment.
AB  - Oral cancer is a type of head and neck cancer that is the seventh most frequent
      cancer and the ninth most frequent cause of death globally. About 90% of oral
      cancer is of squamous cell carcinoma type. Surgery and radiation with and without
      chemotherapy are the major treatments for oral cancer. Better advanced treatment
      is still needed. Multidrug resistance plays an important role in failure of oral
      cancer chemotherapy. In this study, we tried to fabricate a novel nanoparticle
      that could carry both MDR1-siRNA to block MDR1 expression and doxorubicin (DOX),
      a chemotherapy drug, into cancer cells in order to directly kill the cells with
      little or no effect of multidrug resistance. Results showed that mesoporous
      silica nanoparticles (MSNP) can be modified by cationic polymerpolyethylenimine
      (PEI) to obtain positive charges on the surface, which could enable the MSNP to
      carry MDR1-siRNA and DOX. The transfection efficiency assays demonstrated that
      the MSNP-PEI-DOX/ MDR1-siRNA was efficiently transfected into KBV cells in vitro.
      KBV cells transfected with MSNP-PEI-DOX/MDR1-siRNA could effectively decrease
      gene expression of MDR1 (~70% increase after 72 hours posttreatment) and induce
      the apoptosis of KBV cells (24.27% after 48 hours posttreatment) in vitro.
      Importantly, MSNP-PEI-DOX/MDR1-siRNA dramatically reduced the tumor size (81.64%
      decrease after 28 days posttreatment) and slowed down tumor growth rate compared
      to the control group in vivo (P<0.05). In the aggregate, newly synthesized MSNP
      PEI-DOX/MDR1-siRNA improves cancer chemotherapy effect in terms of treating
      multidrug-resistant cancer compared to DOX only, clearly demonstrating that MSNP
      PEI-DOX/MDR1-siRNA has potential therapeutic application for multidrug-resistant
      cancer in the future.

PMID- 29343958
TI  - Preparation of anastrozole loaded PEG-PLA nanoparticles: evaluation of apoptotic
      response of breast cancer cell lines.
AB  - Purpose: Anastrozole (ANS) is an aromatase inhibitor that is widely used as a
      treatment for breast cancer in postmenopausal women. Despite the wide use of ANS,
      it is associated with serious side effects due to uncontrolled delivery. In
      addition, ANS exhibits low solubility and short plasma half-life. Nanotechnology
      based drug delivery has the potential to enhance the efficacy of drugs and
      overcome undesirable side effects. In this study, we aimed to prepare novel ANS
      loaded PLA-PEG-PLA nanoparticles (ANS-NPs) and to compare the apoptotic response
      of MCF-7 cell line to both ANS and ANS-loaded NPs. Method: ANS-NPs were
      synthesized using double emulsion method and characterized using different
      methods. The apoptotic response was evaluated by assessing cell viability,
      morphology, and studying changes in the expression of MAPK3, MCL1, and c-MYC
      apoptotic genes in MCF-7 cell lines. Results: ANS was successfully encapsulated
      within PLA-PEG-PLA, forming monodisperse therapeutic NPs with an encapsulation
      efficiency of 67%, particle size of 186+/-27.13, and a polydispersity index of
      0.26+/-0.11 with a sustained release profile extended over 144 hours. In
      addition, results for cell viability and for gene expression represent a similar
      apoptotic response between the free ANS and ANS-NPs. Conclusion: The synthesized
      ANS-NPs showed a similar therapeutic effect as the free ANS, which provides a
      rationale to pursue pre-clinical evaluation of ANS-NPs on animal models.

PMID- 29343959
TI  - Antitumor effect of a new nano-vector with miRNA-135a on malignant glioma.
AB  - Introduction: MiR-135a is found to selectively induce apoptosis in glioma cell
      but not in normal neurons and glial cells. However, low transfection efficacy
      limits its application in vivo as other miRNAs. We prepared a new kind of nano
      vector based on polyethylene glycol methyl ether (mPEG) and hyper-branched
      polyethylenimine (hy-PEI) in order to improve the miRNA delivery system into the
      glioma cells. Methods: The mPEG-g-PEI/miR-135a was constructed and detected by 1H
      NMR and FTIR analyses. Transmission electron microscope was utilized for its
      characteristics. Stability and release efficiency was assessed by
      electrophoresis. Biocompatibility was observed and analyzed through co-culture
      with astrocytes and malignant glioma cells (C6). Transfection rate was monitored
      by laser confocal microscopy and flow cytometry. The antitumor effect of mPEG-g
      PEI/miR-135a to C6 was confirmed in vivo by MR scanning, pathology and survival
      curve. RT-PCR was used to assay transfection efficiency of mPEG-g-PEI/miR-135a in
      vitro and in vivo. And Western blotting was used to assess the expressions of the
      targeted proteins of miR-135a. Results: In this experiment, we found the optimal
      N/P ratio of mPEG-g-PEI/miR-135a was about 6 judged by Zeta potential, particle
      size and encapsulation ability. The stability of mPEG-g-PEI/miR-135a in serum and
      the release efficiency in acid(pH=5.0) of mPEG-g-PEI/miR-135a were simulated the
      environment in vivo and in tumor. The mPEG-g-PEI nano-vector was co-cultured with
      malignant glioma cell C6 and normal astrocytes in vitro and showed good
      biocompatibility evaluated by CCK8 assay. The cell experiments in vitro indicated
      that mPEG-g-PEI could significantly improve miR-135a transfection by enhancing
      uptake effect of both normal glial and glioma cells. Given the C6 implanted in
      situ model, we discovered that the mPEG-g-PEI/miR-135a could obviously increase
      the survival period and inhibit the growth of glioma confirmed by MRI and
      histochemistry. In addition, the transfection efficiency of mPEG-g-PEI was better
      than that of other transfection agents either in vitro or in vivo confirmed by RT
      PCR. Moreover, the expressions of the targeted proteins of miR-135a were
      consistent with the in vitro results. Conclusion: These results suggest that mPEG
      g-PEI is expected to provide a new effective intracellular miRNA delivery system
      with low toxicity for glioma therapy.

PMID- 29343961
TI  - Receiver operating characteristic curve analysis of the Child Behavior Checklist
      and Teacher's Report Form for assessing autism spectrum disorder in preschool
      aged children.
AB  - Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder
      characterized by social, behavioral, and communication impairments with an
      estimated prevalence of 1 in 68 school-aged children. There is a need for
      objective and easily applicable instruments for early identification of autistic
      children to enable initiation of early interventions during a very sensitive
      period of brain development and, consequently, optimize prognosis. Here, we
      tested the utility of the Child Behavior Checklist (CBCL) and the Caregiver
      Teacher's Report Form (C-TRF) scales for assessing ASD in Brazil, where ASD
      screening research is emergent. Subjects and methods: A total of 70 children (2-5
      years old, both sexes) were enrolled, including an ASD group (n=39) and a non-ASD
      control group (n=31). The preschool versions of the CBCL and C-TRF were applied.
      The CBCL and C-TRF results were compared between the ASD and non-ASD control
      groups with Mann-Whitney U tests and receiver operating characteristic analyses.
      Results: The CBCL and C-TRF were found to have moderate accuracy for the
      dimensions withdrawn and autism spectrum problems, and to correlate with each
      other. Conclusion: The CBCL and C-TRF may aid in early ASD detection.

PMID- 29343960
TI  - Changes of serum uric acid and total bilirubin in elderly patients with major
      postischemic stroke depression.
AB  - Background: This was a longitudinal study which investigated the relationship
      between serum uric acid (SUA) and total bilirubin (Tbil) upon admission in
      elderly stroke patients and the occurrence of postischemic stroke depression
      (IPSD) at 3, 6, and 9 months of post-stroke follow-up. Subjects and methods: Data
      were analyzed for 525 acute ischemic stroke patients. Beck Depression Inventory
      (BDI) scores >17 and Diagnostic and Statistical Manual of Mental Disorders,
      Fourth Edition (DSM-IV) were used separately to screen and diagnose IPSD at 3, 6,
      and 9 months post-stroke. Once IPSD was diagnosed, follow-up activities were
      terminated. Results: High levels of SUA (odds ratio [OR]=2.08, P<0.01) and Tbil
      (OR=2.31, P<0.01) in the first 3 months post-stroke and low levels of SUA
      (OR=2.05, P=0.03) and Tbil (OR=2.79, P<0.01) from 3 to 6 months post-stroke were
      identified as risk factors for major IPSD. At 3 months, patients with SUA levels
      >=406.5 MUmol/L (males with SUA levels of >=409.5 MUmol/L and females with SUA
      levels >=385.5 MUmol/L) and Tbil levels >=23.65 MUmol/L were more likely to
      develop major IPSD. At 6 months, both SUA (area under curve [AUC]=0.625, P=0.005,
      cutoff =194.0 MUmol/L) and Tbil (AUC=0.681, P=0.004, cutoff =6.75 MUmol/L) had
      minor diagnostic values (AUC<0.700), although SUA levels <=214.5 MUmol/L
      (AUC=0.756, P=0.001) in female patients had a good diagnostic value (AUC=0.722,
      P=0.006) for major IPSD. At 9 months, major IPSD showed no statistical
      relationship with either SUA (chi2=2.33, P=0.13) or Tbil (chi2=0.41, P=0.84).
      Conclusion: Higher levels of SUA and Tbil on admission were closely related to
      the occurrence of major IPSD within 3 months of stroke. Lower levels of these two
      biomarkers on admission were characteristic for the occurrence of major IPSD
      between 3 and 6 months post-stroke, while 6 months after stroke, there was no
      relationship between major IPSD and these two biomarkers.

PMID- 29343962
TI  - Functioning outcomes with adjunctive treatments for major depressive disorder: a
      systematic review of randomized placebo-controlled studies.
AB  - Objective: Patients with major depressive disorder (MDD) with inadequate response
      to antidepressant treatment (ADT) may suffer a prolonged loss of functioning.
      This review aimed to determine if self-rated functional measures are informative
      in randomized placebo-controlled studies of adjunctive therapy in patients with
      MDD and inadequate response to ADT. Methods: This was a systematic literature
      review of articles in any language from the MEDLINE database published between
      January 1990 and March 2017. Eligible studies met the following criteria:
      patients with MDD; inadequate response to at least one ADT; adjunctive therapy
      (pharmacological or otherwise) to ADT; placebo control group; randomized
      controlled trial or a post hoc analysis of a randomized controlled trial;
      reported a self-rated functioning scale. Study characteristics and functioning
      efficacy data were extracted. Results: A total of 2,090 discrete records were
      screened, 293 full-text articles were assessed for eligibility, and 26 studies
      were included. All studies were acute (6-12 weeks) except for one 52-week study.
      The only self-rated functioning scale used in the included studies was the
      Sheehan Disability Scale (SDS). Of the 13 adjunctive agents identified,
      aripiprazole, brexpiprazole, edivoxetine, and risperidone improved functioning
      versus placebo (p<0.05), as measured by the SDS total or mean score. On the SDS
      "work/studies" item, only aripiprazole had a statistically significant benefit,
      in one study out of four. Thus, where a benefit was observed on the SDS total or
      mean, this was generally driven by improvement on the "social life" and "family
      life" items. A limitation of the review is that it only considered published
      literature from one database. Conclusion: The SDS, a self-rated functional
      measure, is informative in acute randomized placebo-controlled studies of
      adjunctive therapy in patients with MDD and inadequate response to ADT. However,
      the item that measures work performance may be less relevant to this population
      than the items that measure social and family life.

PMID- 29343963
TI  - Physical factors that influence patients' privacy perception toward a psychiatric
      behavioral monitoring system: a qualitative study.
AB  - Background: Psychiatric patients have privacy concerns when it comes to
      technology intervention in the hospital setting. In this paper, we present
      scenarios for psychiatric behavioral monitoring systems to be placed in
      psychiatric wards to understand patients' perception regarding privacy.
      Psychiatric behavioral monitoring refers to systems that are deemed useful in
      measuring clinical outcomes, but little research has been done on how these
      systems will impact patients' privacy. Methods: We conducted a case study in one
      teaching hospital in Malaysia. We investigated the physical factors that
      influence patients' perceived privacy with respect to a psychiatric monitoring
      system. The eight physical factors identified from the information system
      development privacy model, a comprehensive model for designing a privacy
      sensitive information system, were adapted in this research. Scenario-based
      interviews were conducted with 25 patients in a psychiatric ward for 3 months.
      Results: Psychiatric patients were able to share how physical factors influence
      their perception of privacy. Results show how patients responded to each of these
      dimensions in the context of a psychiatric behavioral monitoring system.
      Conclusion: Some subfactors under physical privacy are modified to reflect the
      data obtained in the interviews. We were able to capture the different physical
      factors that influence patient privacy.

PMID- 29343964
TI  - Achalasia following reflux disease: coincidence, consequence, or accommodation?
      An experience-based literature review.
AB  - Achalasia is a motility disorder of the esophagus characterized by the defective
      peristaltic activity of the esophageal body and impaired relaxation of the lower
      esophageal sphincter due to the degeneration of the inhibitory neurons in the
      myenteric plexus of the esophageal wall. The histopathological and
      pathophysiological changes in achalasia have been well described. However, the
      exact etiological factors leading to the disease still remain unclear. Currently,
      achalasia is believed to be a multifactorial disease, involving both extrinsic
      and intrinsic factors. Based on our experience and the review of literature, we
      believe that gastroesophageal reflux disease (GERD) might be one of the
      triggering factors leading to the development of achalasia. However, it is also
      stated that the two diseases can simultaneously appear independently from each
      other. Considering the large number and routine treatment of patients with GERD
      and achalasia, the rare combination of the two may even remain unnoticed; thus,
      the analysis of larger patient groups with this entity is not feasible. In this
      context, we report four cases where long-standing reflux symptoms preceded the
      development of achalasia. A literature review of the available data is also
      given. We hypothesize that achalasia following the chronic acid exposure of the
      esophagus is not accidental but either a consequence of a chronic inflammation or
      a protective reaction of the organism in order to prevent aspiration and lessen
      reflux-related symptoms. This hypothesis awaits further clinical confirmation.

PMID- 29343966
TI  - Prevalence of antigliadin IgA antibodies in psoriasis vulgaris and response of
      seropositive patients to a gluten-free diet.
AB  - Introduction: The course of psoriasis relies on a variety of metabolic and
      immunological parameters. Identification of underlying pro-inflammatory
      conditions and their control is desired for optimal management. Background:
      Increased prevalence of serum markers for celiac disease has been reported among
      patients with psoriasis. The likelihood of occult celiac disease in a
      subpopulation of patients has been postulated and gluten-free diets have been
      reported to be effective. Patients and methods: The prevalence of gliadin IgA
      antibodies was assessed among patients with psoriasis in an urban population. The
      clinical effects of a strict gluten-free diet were followed. Results: Over a 2
      year period, 97 patients with Psoriasis Area and Severity Index greater than 2.4
      were recruited from a population followed in a dermatology clinic. Gliadin IgA
      antibodies were assessed in all participants and in 91 controls. Elevated gliadin
      IgA antibodies were found in 13 patients (14%) and two controls (2%). Values in
      five patients were assessed as greater than 30.0 U/mL or "strong positive"
      according to the manufacturer of the assay. All 13 patients were placed on a
      strict gluten-free diet without any other modifications in their ongoing
      treatment of psoriasis. Improvement of psoriatic lesions was observed in all
      patients with positive gliadin IgA antibodies but the decline in the Psoriasis
      Area and Severity Index score and the scaling down of pharmaceutical treatment
      was more pronounced in the five patients with strong positive gliadin IgA
      indicating an immune aberration amenable to diet changes. Conclusion: Prevalence
      of antigliadin IgA antibody is significant among patients with psoriasis not
      diagnosed with celiac disease or non-celiac gluten sensitivity. For all its
      limitations, antigliadin IgA testing can identify patients likely to benefit from
      gluten-free diets.

PMID- 29343965
TI  - Postural tachycardia syndrome: current perspectives.
AB  - Postural tachycardia syndrome (POTS) is the combination of an exaggerated heart
      rate response to standing, in association with symptoms of lightheadedness or pre
      syncope that improve when recumbent. The condition is often associated with
      fatigue and brain fog, resulting in significant disruptions at a critical time of
      diagnosis in adolescence and young adulthood. The heterogeneity of the underlying
      pathophysiology and the variable response to therapeutic interventions make
      management of this condition challenging for both patients and physicians alike.
      Here, we aim to review the factors and mechanisms that may contribute to the
      symptoms and signs of POTS and to present our perspectives on the clinical
      approach toward the diagnosis and management of this complex syndrome.

PMID- 29343968
TI  - SUN1 silencing inhibits cell growth through G0/G1 phase arrest in lung
      adenocarcinoma [Retraction].
AB  - [This retracts the article on p. 2825 in vol. 10, PMID: 28652764.].

PMID- 29343967
TI  - Indoleamine 2,3-Dioxygenase Activity Increases NAD+ Production in IFN-gamma
      Stimulated Human Primary Mononuclear Cells.
AB  - IFN-gamma activation of mononuclear phagocytes significantly increases
      indoleamine 2,3-dioxygenase (IDO) and flux through the kynurenine pathway (KP).
      However, the effect of IDO on NAD+ synthesis, the end product of KP metabolism,
      is unknown. To investigate this, primary human peripheral blood mononuclear cells
      were cultured up to 10 days and activated with IFN-gamma in the presence or
      absence of a poly(ADP-ribose) polymerase (PARP) inhibitor. Day 10 macrophages had
      significantly higher NAD+ levels compared with monocytes. IFN-gamma activation of
      macrophages resulted in the highest induction of IDO but decreased intracellular
      NAD+ concentrations at both 24 and 48 hours. However, IFN-gamma activation of
      both day 6 and day 10 macrophages in the presence of a PARP inhibitor resulted in
      significantly higher intracellular NAD+ levels at 24 hours. This study provides
      evidence for the first time that an immune-mediated increase in IDO activity
      increases NAD+ biosynthesis concomitantly with an increase in NAD+ catabolism in
      primary human macrophages.

PMID- 29343969
TI  - The putative tumor suppressor, miR-199a, regulated by Snail, modulates clear cell
      renal cell carcinoma aggressiveness by repressing ROCK1.
AB  - Background: Aberrant expression of miR-199a has been frequently reported in
      cancer studies; however, its role in renal cell carcinoma (RCC) has not been
      examined in detail. Results: Here, we showed that miR-199a was downregulated in
      RCC and associated with poor prognostic phenotype. Using luciferase and western
      blot assays we identified that Rho-associated coiled coil-containing protein
      kinases 1 (ROCK1) was a direct target gene for miR-199a. miR-199a regulated
      proliferation, invasion, and apoptosis of clear cell renal cell carcinoma (ccRCC)
      cells by modulating ROCK1 expression. Interestingly, we also found that miR-199a
      was modulated by snail in ccRCC cells. Snail elevated ROCK1 expression by
      repressing miR-199a activity. Conclusion: Altogether, our results identify a
      crucial tumor suppressive role of miR-199a in the progression of ccRCC and
      suggest that miR-199a might be an anticancer therapeutic target for ccRCC
      patients.

PMID- 29343970
TI  - A retrospective examination of the US Food and Drug Administration's clinical
      pharmacology reviews of oncology biologics for potential use of therapeutic drug
      monitoring.
AB  - Background: Biologics have gained traction for use in oncology, but have
      demonstrate clinical variability for efficacy and safety. Therapeutic drug
      monitoring (TDM) can benefit patients' outcomes from a biologic therapy when the
      latter has a defined therapeutic window. A clinically relevant therapeutic window
      may exist for biologics with established exposure-response (E-R) relationships
      for efficacy and/or safety and a documented maximum tolerated dose (MTD).
      Additionally, the inter-individual variability (IIV) on the clearance (CL)
      parameter could determine risks for patients falling outside the proposed
      therapeutic window. Materials and methods: The US Food and Drug Administration
      (FDA)-approved oncology biologics between 2005-2016 were reviewed via FDA "Purple
      Book" (FDA-repository for licensed biologics). Data were extracted from
      biologics' pharmacokinetic models available on the clinical pharmacology reviews
      published on the FDA-Approved Drug Products website. Evaluated features for
      biologics with established E-R relationships for efficacy and/or safety and MTD
      include an IIV for the CL and various other covariates including demographic
      factors, disease factors, blood chemistry, or immunogenicity. Results: Five
      therapies were identified with documented E-R relationships for both efficacy and
      safety including, Yervoy(r)(ipilimumab), Zaltrap(r) (ziv-aflibercept),
      Portrazza(r) (necitumumab), Adcetris(r) (brentuximab-vedotin), and Blincyto(r)
      (blinatumomab). The corresponding IIV on CL were: 34%, 33%, 29%, 47%, and 97%,
      respectively. Among the five therapies, only three had defined MTD including,
      brentuximab-vedotin, necitumumab, and blinatumomab. Conclusion: Of the
      medications examined, blinatumomab was identified as the anticancer drug with the
      most available information for the establishment of TDM, and hence, may benefit
      through the use of TDM to optimize effectiveness and minimize patients' toxicity.
      The approach used here may provide a generalizable framework to retrospectively
      identify anticancer biologics with high IIV that may benefit from TDM to improve
      patients' clinical outcome.

PMID- 29343971
TI  - Assessment of the cardiac safety between cetuximab and panitumumab as single
      therapy in Chinese chemotherapy-refractory mCRC.
AB  - Objective: The cardiac safety of cetuximab and panitumumab, particularly as
      single agents, has not been investigated extensively. This trial was designed to
      specifically evaluate the cardiac safety of cetuximab and panitumumab as single
      therapy in Chinese chemotherapy-refractory metastatic colorectal cancer (mCRC)
      patients. Patients and methods: Sixty-one patients received cetuximab at an
      initial dose of 400 mg/m2 intravenously over 120 minutes on day 1 (week 1),
      followed by a maintenance dose of 250 mg/m2 intravenously over 60 minutes on day
      1 of each 7-day cycle. Forty-three patients received panitumumab at a dose of 6
      mg/kg intravenously every 14 days. Routine laboratory tests and electrocardiogram
      (ECG) were performed at baseline, during therapy and after the treatment (4th and
      10th months). The incidence of elevation of troponin I ultra (TNI Ultra),
      abnormal ECGs, cardiac events and noncardiac adverse events (AEs) were recorded
      and analyzed. Results: The incidence of elevation of TNI Ultra between the two
      groups had no significance (p=0.681), and TNI Ultra+ was observed more frequently
      in patients with metastases to more than three organs and they received fourth or
      above lines of chemotherapy. The most frequent abnormal ECG manifestations were
      nonspecific ST changes and QTc prolongation in the two groups. At 10 months after
      treatment, most of the abnormal ECG manifestations were reversed. The most common
      cardiac AEs of cetuximab and panitumumab included palpitations, dyspnea, chest
      pain and arrhythmias requiring treatment. Most of the events were mild and
      transient. The incidence of cardiac AEs had no significant difference between the
      two groups. Rash was still the most common noncardiac AE in both groups.
      Conclusion: Cetuximab and panitumumab showed favorable cardiac safety as single
      agents for Chinese chemotherapy-refractory mCRC patients. But monitoring for
      cardiac AEs is still necessary throughout the entire treatment process.

PMID- 29343973
TI  - A patient with classic biphasic pulmonary blastoma harboring CD74-ROS1 fusion
      responds to crizotinib.
AB  - Pulmonary blastoma (PB) is a rare aggressive lung malignancy with a poor
      prognosis. Surgical resection is the treatment of choice for localized disease,
      and there are no standard treatment guidelines for metastatic PB. Due to its
      rareness, its molecular profile has not been elucidated. We present the first
      case of classic biphasic pulmonary blastoma (CBPB) with CD74-ROS1 rearrangement
      in a 44-year-old Asian female with stage IV disease diagnosed using capture-based
      ultra-deep targeted sequencing. It has been reported that ROS1 rearranged lung
      adenocarcinoma and squamous cell carcinoma are sensitive to crizotinib, an
      ALK/MET/ ROS1 multitargeted tyrosine kinase inhibitor. However, its efficacy has
      not been reported in CBPB patients harboring ROS1 rearrangement. This CBPB
      patient was given crizotinib and she achieved partial response after 1 month of
      treatment. We report the first clinical evidence of efficacy shown by crizotinib
      for targeting CD74-ROS1 fusion in CBPB.

PMID- 29343972
TI  - Targeting histone methyltransferase and demethylase in acute myeloid leukemia
      therapy.
AB  - Acute myeloid leukemia (AML) is a clonal disorder of myeloid progenitors
      characterized by the acquisition of chromosomal abnormalities, somatic mutations,
      and epigenetic changes that determine a consistent degree of biological and
      clinical heterogeneity. Advances in genomic technologies have increasingly shown
      the complexity and heterogeneity of genetic and epigenetic alterations in AML.
      Among the genetic alterations occurring in AML, frequent are the genetic
      alterations at the level of various genes involved in the epigenetic control of
      the DNA methylome and histone methylome. In fact, genes involved in DNA
      demethylation (such as DNMT3A, TET2, IDH1, and IDH2) or histone methylation and
      demethylation (EZH2, MLL, DOT1L) are frequently mutated in primary and secondary
      AML. Furthermore, some histone demethylases, such as LSD1, are frequently
      overexpressed in AML. These observations have strongly supported a major role of
      dysregulated epigenetic regulatory processes in leukemia onset and development.
      This conclusion was further supported by the observation that mutations in genes
      encoding epigenetic modifiers, such as DMT3A, ASXL1, TET2, IDH1, and IDH2, are
      usually acquired early and are present in the founding leukemic clone. These
      observations have contributed to development of the idea that targeting
      epigenetic abnormalities could represent a potentially promising strategy for the
      development of innovative treatments of AML. In this review, we analyze those
      proteins and their inhibitors that have already reached the first stages of
      clinical trials in AML, namely the histone methyltransferase DOT1L, the
      demethylase LSD1, and the MLL-interacting protein menin.

PMID- 29343974
TI  - Identification of key pathways and genes in TP53 mutation acute myeloid leukemia:
      evidence from bioinformatics analysis.
AB  - Background: Tumor protein p53 (TP53) mutations are not only a risk factor in
      acute myeloid leukemia (AML) but also a potential biomarker for individualized
      treatment options. This study aimed to investigate potential pathways and genes
      associated with TP53 mutations in adult de novo AML. Methods: An RNA sequencing
      dataset of adult de novo AML was downloaded from The Cancer Genome Atlas
      database. Differentially expressed genes (DEGs) were identified by edgeR of the R
      platform. Key pathways and genes were identified using the following
      bioinformatics tools: gene set enrichment analysis (GSEA), gene ontology (GO),
      the Kyoto Encyclopedia of Genes and Genomes (KEGG), Search Tool for the Retrieval
      of Interacting Genes/Proteins, and Molecular Complex Detection. Results: GSEA
      suggested that TP53 mutations were significantly associated with cell
      differentiation, proliferation, cell adhesion biological processes, and MAPK
      pathway. In total, 1,287 genes were identified as DEGs. GO and KEGG analysis
      suggested that upregulation of DEGs was significantly enriched in categories
      associated with cell adhesion biological processes, Ras-associated protein 1,
      PI3K-Akt pathway, and cell adhesion molecules. The top ten genes ranked by
      degree, CDH1, BMP2, KDR, LEP, CASR, ITGA2B, APOE, MNX1, NMU, and TRH, were
      identified as hub genes from the protein-protein interaction network. Survival
      analysis suggested that patients with TP53 mutations had a significantly
      increased risk of death, while the mRNA expression level in patients with TP53
      mutation was similar to those carrying TP53 wild type. Conclusion: Our findings
      have indicated that multiple genes and pathways may play a crucial role in TP53
      mutation AML, offering candidate targets and strategies for TP53 mutation AML
      individualized treatment.

PMID- 29343975
TI  - Spotlight on midostaurin in the treatment of FLT3-mutated acute myeloid leukemia
      and systemic mastocytosis: design, development, and potential place in therapy.
AB  - The Fms-like tyrosine kinase-3 (FLT3; fetal liver kinase-2; human stem cell
      tyrosine kinase-1; CD135) is a class III receptor tyrosine kinase that is
      normally involved in regulating the proliferation, differentiation, and survival
      of both hematopoietic cells and dendritic cells. Mutations leading it to be
      constitutively activated make it an oncogenic driver in ~30% of acute myeloid
      leukemia (AML) patients where it is associated with poor prognosis. The
      prevalence of oncogenic FLT3 and the dependency on its constitutively activated
      kinase activity for leukemia growth make this protein an attractive target for
      therapeutic intervention. Of the numerous small molecule inhibitors under
      clinical investigation for the treatment of oncogenic FLT3-positive AML, the N
      benzoyl-staurosporine, midostaurin (CGP41251; PKC412; Rydapt(r); Novartis Pharma
      AG, Basel, Switzerland), is the first to be approved by the US Food and Drug
      Administration for the treatment, in combination with standard chemotherapy, of
      newly diagnosed adult AML patients who harbor mutations in FLT3. Here, we
      describe the early design of midostaurin, the preclinical discovery of its
      activity against oncogenic FLT3, and its subsequent clinical development as a
      therapeutic agent for FLT3 mutant-positive AML.

PMID- 29343976
TI  - Epidemiology, associated burden, and current clinical practice for the diagnosis
      and management of Alzheimer's disease in Japan.
AB  - The burden of dementia in Japan is large and growing. With the world's fastest
      aging population, it is estimated that one in five elderly people will be living
      with dementia in Japan by 2025. The most common form of dementia is Alzheimer's
      disease (AD), accounting for around two-thirds of dementia cases. A systematic
      review was conducted to examine the epidemiology and associated burden of AD in
      Japan and to identify how AD is diagnosed and managed in Japan. English and
      Japanese language databases were searched for articles published between January
      2000 and November 2015. Relevant Japanese sources, clinical practice guideline
      registers, and reference lists were also searched. Systematic reviews and cohort
      and case-control studies were eligible for inclusion, with a total of 60 studies
      included. The most recent national survey conducted in six regions of Japan
      reported the mean prevalence of dementia in people aged >=65 years to be 15.75%
      (95% CI: 12.4, 22.2%), which is much higher than the previous estimated rate of
      10% in 2010. AD was confirmed as the predominant type of dementia, accounting for
      65.8% of all cases. Advancing age and low education were the most consistently
      reported risk factors for AD dementia. Japanese guidelines for the management of
      dementia were released in 2010 providing specific guidance for AD about clinical
      signs, image findings, biochemical markers, and treatment approaches.
      Pharmacotherapies and non-pharmacotherapies to relieve cognitive symptoms were
      introduced, as were recommendations to achieve better patient care. No studies
      reporting treatment patterns were identified. Due to population aging and growing
      awareness of AD in Japan, health care expenditure and associated burden are
      expected to soar. This review highlights the importance of early detection,
      diagnosis, and treatment of AD as strategies to minimize the impact of AD on
      society in Japan.

PMID- 29343977
TI  - Cost-effectiveness analysis of six therapies for the treatment of lower urinary
      tract symptoms due to benign prostatic hyperplasia.
AB  - Objective: To conduct a cost-effectiveness analysis from payers' perspectives of
      six treatments for lower urinary tract symptoms (LUTS) associated with benign
      prostatic hyperplasia (BPH) and to examine positioning of these modalities in the
      marketplace for the best use of health care funds and quality-of-life benefits
      for patients. Methods: The economic analysis was conducted with a Markov model to
      compare combination prescription drug therapy (ComboRx), minimally invasive
      therapies (MITs) including convective radiofrequency (RF) water vapor thermal
      therapy (Rezum(r)), conductive RF thermal therapy (Prostiva(r)), and prostatic
      urethral lift (UroLift(r)), and invasive surgical procedures including
      photovaporization of the prostate (Greenlight(r) PVP) and transurethral resection
      of the prostate (TURP). Effects assessed with International Prostate Symptom
      Score, adverse events, and re-treatment rates were estimated from medical
      literature; treatments effects were modeled using a common baseline score.
      Starting with each therapy, patients' transitions to more intensive therapies
      when symptoms returned were simulated in 6-month cycles over 2 years. Incremental
      cost-effectiveness ratios (ICERs) were calculated for pairs of treatments;
      uncertainty in ICERs was estimated with probabilistic sensitivity analyses.
      Results: ComboRx was least effective and provided one-third of the symptom relief
      achieved with MITs. UroLift was similar in effectiveness to Prostiva and Rezum
      but costs more than twice as much. The cheaper MITs were ~$900 more expensive
      than the cost of ComboRx generic drugs over 2 years. TURP and PVP provided
      slightly greater relief of LUTS than MITs at approximately twice the cost over 2
      years; typically, they are reserved for treatment of more severe LUTS.
      Conclusion: The analysis evaluated the costs and symptom relief of six treatment
      options in the continuum of care from a common baseline of LUTS severity.
      Identification of treatments for LUTS/BPH that demonstrate cost-effectiveness and
      provide appreciable symptom relief is paramount as reimbursement for patient care
      moves from volume-based services to value-based services.

PMID- 29343978
TI  - Parietal scalp is another affected area in female pattern hair loss: an analysis
      of hair density and hair diameter.
AB  - Purpose: Female pattern hair loss (FPHL) is a common hair disease. However,
      studies of the quantitative measurement of FPHL are still limited. The aim of
      this study was to investigate the characteristics of hair density and hair
      diameter in normal women and FPHL patients, and further correlate the
      quantitative measurement with the clinical presentation of FPHL. Patients and
      methods: An evaluation of 471 FPHL patients and 236 normal women was carried out
      according to the Ludwig classification, and analysis was performed by using a com
      puterized handheld USB camera with computer-assisted software. Various areas of
      the scalp, including frontal, parietal, midscalp, and occipital, were analyzed
      for hair density, non-vellus hair diameter, and percentage of miniaturized hair.
      Results: The hair density in normal women was the highest and the lowest in the
      midscalp and parietal areas, respectively. The FPHL group revealed the lowest
      hair density in the parietal area. Significant differences in hair density, non
      vellus hair diameter, and percentage of miniaturized hair between the normal and
      FPHL groups were observed, especially in the midscalp and parietal areas.
      Conclusion: The parietal area is another important affected area in FPHL in
      addition to the midscalp area. This finding provides novel important information
      of FPHL and will be useful for hair transplant surgeons choosing the optimal
      donor sites for hair transplantation in women.

PMID- 29343979
TI  - The influence of CYP3A5 polymorphisms on haloperidol treatment in patients with
      alcohol addiction.
AB  - Background: Isoenzymes CYP2D6 and CYP3A4, the activity of which varies widely,
      are involved in metabolism of haloperidol and may influence its profile of
      efficacy and safety. Objective: The primary aim of this study was to estimate the
      relationship between CYP3A5 gene polymorphism, activity of the CYP3A isoenzyme,
      and the risk of development of adverse drug reactions by haloperidol in patients
      with alcohol abuse. Methods: Sixty-six male alcohol-addicted patients
      participated in the study. The safety of haloperidol was evaluated by Udvalg for
      Kliniske Undersogelser Side Effect Rating Scale (UKU) and Simpson-Angus Scale for
      extrapyramidal symptoms (SAS). The activity of CYP3A was evaluated by determining
      the concentrations of an endogenous substrate of this isoenzyme (cortisol) and
      its urinary metabolite (6-beta-hydroxycortisol, 6-B-HC). Genotyping of CYP3A5*3
      was performed by real-time polymerase chain reaction with allele-specific
      hybridization. Results: The frequency of A-allele occurrence in Russian
      population was very poor (2.27%). CYP3A5*3 polymorphism had no influence on
      safety profile indicators of haloperidol (UKU scale: p=0.55, SAS scale: p=0.64).
      In addition, there was no statistical significant difference between the values
      of indexes of the metabolic ratio (6-B-HC/cortisol) in groups with different
      genotypes of CYP3A5*3: GG 5.00 (3.36; 6.39) vs AG 5.26 (2.10; 6.78) (p=0.902).
      Conclusion: The frequency of A-allele occurrence of CYP3A5*3 in Russian
      population is very poor, and it has no high influence on the safety of
      haloperidol treatment; therefore, there are no reasons to take this polymorphism
      into account in patients with alcohol addiction who receive haloperidol.

PMID- 29343980
TI  - Peripheral and spinal TRPA1 channels contribute to formalin-induced long-lasting
      mechanical hypersensitivity.
AB  - Background: Transient receptor potential ankyrin 1 (TRPA1) is a non-selective
      cation channel expressed by a subset of nociceptive neurons that acts as a
      multimodal receptor. Its activity contributes to modulate nociceptive
      transmission in acute inflammatory pain. However, the role of this channel in
      chronic pain has been less studied. The purpose of this study was to investigate
      the local peripheral and spinal participation of TRPA1 channels in formalin
      induced long-lasting hypersensitivity. Materials and methods: Formalin (1%)
      induced chronic hypersensitivity was determined by the application of von Frey
      filaments to ipsilateral and contralateral paws and through pharmacological
      testing using a selective TRPA1 blocker (A-967079). TRPA1 expression in the
      dorsal root ganglion (DRG) and spinal cord was analyzed by Western blotting.
      Results: Formalin (1%) injection produced acute flinching behavior (1 h) as well
      as secondary allodynia and hyperalgesia (12 days). Local peripheral pretreatment
      (10 min before) or posttreatment (6 days later) with A-967079 (1-100 uM)
      partially prevented and reversed, respectively, in a dose-dependent manner, long
      lasting secondary mechanical allodynia and hyperalgesia evoked by 1% formalin.
      Likewise, intrathecal pretreatment or posttreatment with A-967079 partially
      prevented and reversed, respectively, formalin-induced long-lasting
      hypersensitivity. A-967079 (100 uM) completely abolished the pro-nociceptive
      effect of formalin (adjusted to pH 7.4). Finally, formalin injection increased
      TRPA1 protein expression in the DRG and spinal cord. Conclusion: Results indicate
      that TRPA1 expressed in the DRG and spinal cord plays a relevant role in formalin
      induced long-lasting secondary nociceptive hypersensitivity.

PMID- 29343981
TI  - Assessment of pain score and specimen adequacy for ultrasound-guided fine-needle
      aspiration biopsy of thyroid nodules.
AB  - Objective: The aim of this study was to evaluate pain scores and specimen
      adequacy for ultrasound-guided fine-needle aspiration biopsy (US-FNAB) of thyroid
      nodules without and with local anesthesia (LA). Materials and methods: The US
      FNAB procedure was performed on 183 patients with and without LA. One puncture
      was made for solid nodules, and if patients could tolerate it, a two-puncture
      technique was used for nodules with a cystic change. Four-point verbal rating
      scores were assessed by a nursing assistant after completion of US-FNAB. To be an
      adequate specimen, at least six groups of follicular cells are required, and each
      group should contain at least 10 cells. Results: Immediately after US-FNAB, 92%
      of patients with LA and 80% without LA reported no or mild pain (p=0.01). Most
      patients tolerated the procedure well, with no pain (82.5%) reported 5 minutes
      after the procedure. In univariate logistic regression, irregular boundary (odds
      ratio [OR]: 2.52, 95% confidence interval [CI]: 1.04-6.06, p=0.04), calcification
      (OR: 2.86, 95% CI: 1.06-7.76, p=0.04), and LA (OR: 0.35, 95% CI: 0.15-0.86,
      p=0.02) were significantly associated with immediate moderate or severe pain.
      Specimen adequacy was significantly associated with age (OR: 0.95, 95% CI: 0.92
      0.97, p<0.01), heterogeneous echo-texture (OR: 1.76, 95% CI: 1.23-5.17, p=0.01),
      predominate solid architecture (OR: 2.78, 95% CI: 1.42-5.41, p<0.01), and the use
      of LA (OR: 3.34, 95% CI: 1.70-6.56, p<0.01). In multivariate logistic regression,
      patients receiving LA had lower risk of moderate or severe pain (OR: 0.25, 95%
      CI: 0.09-0.67, p=0.01) and higher chances of specimen adequacy (OR: 4.84, 95% CI:
      2.17-10.7, p<0.01) compared to patients who did not receive LA. Conclusion: US
      FNAB is a safe procedure, and most patients report no pain 5 minutes after the
      procedure. The use of LA was associated with lower immediate pain scales and
      higher specimen adequacy.

PMID- 29343983
TI  - Does transcutaneous electrical nerve stimulation reduce pain and improve quality
      of life in patients with idiopathic chronic orchialgia? A randomized controlled
      trial.
AB  - Background: Chronic orchialgia is defined as testicular pain, which may be either
      unilateral or bilateral, lasting for more than 3 months. It disturbs a patient's
      daily activities and quality of life (QoL), inciting the patient to search for
      treatments to alleviate the pain. It is estimated that 25% of chronic orchialgia
      cases are idiopathic. Purpose: The purpose of this study was to investigate how
      effective transcutaneous electrical nerve stimulation (TENS) is in pain reduction
      and how it consequently affects the QoL in patients with idiopathic chronic
      orchialgia (ICO). Patients and methods: Seventy-one patients were randomly
      assigned to group A (study group), which included 36 patients who received TENS
      and analgesia, and group B (control group), which included 35 patients who
      received analgesia only. The outcome measures were the participants' demographic
      data and results of the visual analog scale (VAS) and QoL questionnaire. These
      outcomes were measured before and after 4 weeks of treatment and at 2-month
      follow-up. Results: The results showed that compared to pretreatment, there was a
      significant reduction in pain postintervention and at 2-month follow-up in group
      A (P<0.0001 and <0.001, respectively; F=7.1) as well as a significant improvement
      in QoL at these time points (P<0.0001 and <0.0001, respectively). There were no
      significant differences in the VAS score and QoL in group B at different time
      points of evaluation. Conclusion: The findings indicate that TENS is effective in
      reducing pain and improving patients' QoL in cases of ICO. TENS is an easy-to
      use, effective, noninvasive, and simple method for ICO-associated pain control
      and QoL improvement.

PMID- 29343982
TI  - Increased theta band EEG power in sickle cell disease patients.
AB  - Objective: Pain is a major issue in the care of patients with sickle cell disease
      (SCD). The mechanisms behind pain and the best way to treat it are not well
      understood. We studied how electroencephalography (EEG) is altered in SCD
      patients. Methods: We recruited 20 SCD patients and compared their resting state
      EEG to that of 14 healthy controls. EEG power was found across frequency bands
      using Welch's method. Electrophysiological source imaging was assessed for each
      frequency band using the eLORETA algorithm. Results: SCD patients had increased
      theta power and decreased beta2 power compared to controls. Source localization
      revealed that areas of greater theta band activity were in areas related to pain
      processing. Imaging parameters were significantly correlated to emergency
      department visits, which indicate disease severity and chronic pain intensity.
      Conclusion: The present results support the pain mechanism referred to as
      thalamocortical dysrhythmia. This mechanism causes increased theta power in
      patients. Significance: Our findings show that EEG can be used to quantitatively
      evaluate differences between controls and SCD patients. Our results show the
      potential of EEG to differentiate between different levels of pain in an unbiased
      setting, where specific frequency bands could be used as biomarkers for chronic
      pain.

PMID- 29343984
TI  - Appropriateness of sham or placebo acupuncture for randomized controlled trials
      of acupuncture for nonspecific low back pain: a systematic review and meta
      analysis.
AB  - Objectives: To establish whether sham acupuncture (SA) or placebo acupuncture
      (PA) is more efficacious for reducing low back pain (LBP) than other routine
      treatments and to discuss whether SA or PA is appropriate for randomized
      controlled trials of acupuncture for LBP. Methods: Six databases were searched on
      31 May 2017. We included only randomized controlled trials of adults with LBP and
      lower back myofascial pain syndrome. The studies had at least two control arms: a
      sham-controlled acupuncture arm and a routine care or waiting list arm (people
      who did not receive acupuncture until the end of treatment). Trials were combined
      using meta-analysis methods when the data allowed statistical pooling. Pooled
      effect sizes were calculated by random effects models. Results: This review
      identified 7 trials (1768 participants); all were included in the meta-analysis.
      We found statistically significant differences in pain reduction post
      intervention between SA or PA and routine care or a waiting list, with a
      standardized mean difference of -0.36 (95% CI -0.54 to -0.18; I2 statistic=16%;
      participants=624; studies=6) for the Visual Analog Scale and -0.35 (95% CI -0.49
      to -0.20; I2 statistic=0%; participants=736; studies=1) for the Chronic Pain
      Grade Scale; however, no significant difference was observed between SA or PA and
      routine care or no treatment for post-intervention function. Conclusion: Compared
      with routine care or a waiting list, SA or PA was more efficacious for pain
      relief post-intervention. Concluding that SA or PA is appropriate for acupuncture
      research would be premature. Guidelines evaluating SA or PA control methods are
      needed to determine the specific effect of acupuncture over placebo.

PMID- 29343985
TI  - Bioactive chromone constituents from Vitex negundo alleviate pain and
      inflammation.
AB  - Background: Vitex negundo L. has been widely studied for its beneficial effect in
      inflammatory and pain conditions. The present study describes the isolation of
      two new bioactive chromone constituents from V. negundo and their in vivo
      evaluation for anti-inflammatory and antinociceptive activities. Methods: Two new
      chromone derivatives, namely, methyl 3-(2-(5-hydroxy-6-methoxy-4-oxo-4H-chromen-2
      yl)ethyl)benzoate (1) and 3-(1-hydroxy-2-(5-hydroxy-6-methoxy-4-oxo-4H-chromen-2
      yl)ethyl)benzoic acid (2) were isolated from V. negundo and their structures were
      determined through various spectroscopic techniques including mass spectrometry,
      UV, IR, 1H NMR, 13C NMR, and two-dimensional-NMR like correlation spectroscopy
      and heteronuclear multiple bond correlation techniques. The isolated compounds (1
      2) were tested for their prospective antinociceptive activity in acetic acid
      induced abdominal constriction assay and anti-inflammatory activity in the
      carrageenan-induced paw edema assay in mice. Results: Significant attenuation
      (P<0.001) of tonic visceral nociception was demonstrated by compound 1 and 2 at
      doses of 50 and 100 mg/kg. At similar doses, these compounds (1-2) also showed
      potent amelioration (P<0.001) of carrageenan-induced paw swelling. Conclusion:
      The isolated chromone derivatives (1-2) from V. negundo are able to alleviate
      nociception and inflammation and the findings corroborated that V. negundo may be
      used as a potential source of antinociceptive and anti-inflammatory candidates.

PMID- 29343986
TI  - Radiotherapy for esophageal carcinoma: dose, response and survival.
AB  - Esophageal cancer (EC) is an extremely aggressive, lethal malignancy that is
      increasing in incidence worldwide. At present, definitive chemoradiotherapy is
      accepted as the standard treatment for locally advanced EC. The EC guidelines
      recommend a radiation dose of 50.4 Gy for definitive treatment, yet the outcomes
      for patients who have received standard-dose radiotherapy remain unsatisfactory.
      However, some studies indicate that a higher radiation dose could improve local
      tumor control, and may also confer survival benefits. Some studies, however,
      suggest that high-dose radiotherapy does not bring survival benefit. The
      available data show that most failures occurred in the gross target volume
      (especially in the primary tumor) after definitive chemoradiation. Based on those
      studies, we hypothesize that at least for some patients, more intense local
      therapy may lead to better local control and survival. The aim of this review is
      to evaluate the radiation dose, fractionation strategies, and predictive factors
      of response to therapy in functional imaging for definitive chemoradiotherapy in
      esophageal carcinoma, with an emphasis on seeking the predictive model of
      response to CRT and trying to individualize the radiation dose for EC patients.

PMID- 29343987
TI  - Performance of the LACE index to predict 30-day hospital readmissions in patients
      with chronic obstructive pulmonary disease.
AB  - Background and objective: Patients hospitalized for acute exacerbation of chronic
      obstructive pulmonary disease (COPD) have a high 30-day hospital readmission
      rate, which has a large impact on the health care system and patients' quality of
      life. The use of a prediction model to quantify a patient's risk of readmission
      may assist in directing interventions to patients who will benefit most. The
      objective of this study was to calculate the rate of 30-day readmissions and
      evaluate the accuracy of the LACE index (length of stay, acuity of admission, co
      morbidities, and emergency department visits within the last 6 months) for 30-day
      readmissions in a general hospital population of COPD patients. Methods: All
      patients admitted with a principal diagnosis of COPD to Liverpool Hospital, a
      tertiary hospital in Sydney, Australia, between 2006 and 2016 were included in
      the study. A LACE index score was calculated for each patient and assessed using
      receiver operator characteristic curves. Results: During the study period, 2,662
      patients had 5,979 hospitalizations for COPD. Four percent of patients died in
      hospital and 25% were readmitted within 30 days; 56% of all 30-day readmissions
      were again due to COPD. The most common reasons for readmission, following COPD,
      were heart failure, pneumonia, and chest pain. The LACE index had moderate
      discriminative ability to predict 30-day readmission (C-statistic =0.63).
      Conclusion: The 30-day hospital readmission rate was 25% following
      hospitalization for COPD in an Australian tertiary hospital and as such
      comparable to international published rates. The LACE index only had moderate
      discriminative ability to predict 30-day readmission in patients hospitalized for
      COPD.

PMID- 29343988
TI  - Does breast density measured through population-based screening independently
      increase breast cancer risk in Asian females?
AB  - Purpose: The purpose of this study was to investigate the effects of breast
      density on breast cancer risk among women screened via a nationwide mammographic
      screening program. Patients and methods: We conducted a nested case-control study
      for a randomly selected population of 1,561 breast cancer patients and 6,002
      matched controls from the National Cancer Screening Program. Breast density was
      measured and recorded by two independent radiologists using the Breast Imaging
      Reporting and Data System (BI-RADS). Associations between BI-RADS density and
      breast cancer risk were evaluated according to screening results, time elapsed
      since receiving non-recall results, age, and menopausal status after adjusting
      for possible covariates. Results: Breast cancer risk for women with extremely
      dense breasts was five times higher (adjusted odds ratio [aOR] =5.0; 95%
      confidence interval [CI]) =3.7-6.7) than that for women with an almost entirely
      fatty breast, although the risk differed between recalled women (aOR =3.3, 95% CI
      =2.3-3.6) and women with non-recalled results (aOR =12.1, 95% CI =6.3-23.3, P
      heterogeneity =0.001). aORs for BI-RADS categories of breast density were similar
      when subjects who developed cancer after showing non-recall findings during
      initial screening were grouped according to time until cancer diagnosis
      thereafter (<1 and >=1 year). The prevalence of dense breasts was higher in
      younger women, and the association between a denser breast and breast cancer was
      stronger in younger women (heterogeneously dense breast: aOR =7.0, 95% CI =2.4
      20.3, women in their 40s) than older women (aOR =2.5, 95% CI =1.1-6.0, women in
      their 70s or more). In addition, while the positive association remained,
      irrespective of menopausal status, the effect of a dense breast on breast cancer
      risk was stronger in premenopausal women. Conclusion: This study confirmed an
      increased risk of breast cancer with greater breast density in Korean women which
      was consistent regardless of BI-RADS assessment category, time interval after
      initially non-recall results, and menopausal status.

PMID- 29343989
TI  - Comparison of the performance of five screening methods for sarcopenia.
AB  - Background: Sarcopenia leads to serious adverse health consequences. There is a
      dearth of screening tools for this condition, and performances of these
      instruments have rarely been evaluated. Our aim was to compare the performance of
      five screening tools for identifying elders at risk of sarcopenia against five
      diagnostic definitions. Subjects and methods: We gathered cross-sectional data of
      elders from the SarcoPhAge ("Sarco"penia and "Ph"ysical Impairment with Advancing
      "Age") study. Lean mass was measured with X-ray absorptiometry, muscle strength
      with a dynamometer and physical performance with the Short Physical Performance
      Battery (SPPB) test. Performances of screening methods were described using
      sensitivity, specificity, positive predictive value (PPV), negative predictive
      value (NPV) and area under the curve (AUC), according to five diagnostic
      definitions of sarcopenia. For each screening tool, optimal cutoff points were
      computed using two methods. Results: A total of 306 subjects (74.8+/-5.9 years,
      59.5% women) were included. The prevalence of sarcopenia varied from 5.7% to
      16.7% depending on the definition. The best sensitivity (up to 100%) and the best
      NPV (up to 99.1%) were obtained with the screening test of Ishii et al,
      regardless of the definition applied. The highest AUC (up to 0.914) was also
      demonstrated by the instrument of Ishii et al. The most specific tool was the
      algorithm of the European Working Group on Sarcopenia in Older People (EWGSOP; up
      to 91.1%). All NPVs were above 87.0%, and all PPVs were below 51.0%. New cutoffs
      related to each screening instrument were also proposed to better discriminate
      sarcopenic individuals from non-sarcopenic individuals. Conclusion: Screening
      instruments for sarcopenia can be relevantly used in clinical practice to make
      sure to identify individuals who do not suffer from the syndrome. The screening
      test of Ishii et al showed better properties in terms of distinguishing those at
      risk of sarcopenia from those who were not at risk.

PMID- 29343990
TI  - Emerging evidence on the link between depressive symptoms and bone loss in
      postmenopausal women.
AB  - Osteoporosis and depression are major health problems of crisis proportions in
      postmenopausal women. Researchers have established a relationship between bone
      loss and depression, although few studies have focused on postmenopausal women.
      The purposes of this integrative review were to synthesize and summarize the
      available literature on: 1) the associations between bone loss and depression in
      postmenopausal women; and 2) potential variables that impact the associations
      between bone loss and depression in postmenopausal women. After searching the
      databases PubMed, CINAHL, Embase, and the Cochrane library between 2007 and 2017,
      12 articles met the inclusion criteria. The majority of the included studies
      supported the relationship between depression and bone loss in postmenopausal
      women, although little information is offered as to why this relationship exists.
      This review summarizes the research that has been completed on depression and
      bone loss in postmenopausal women and identifies gaps in the literature. These
      findings will aid in the planning of future research and the development of
      health care recommendations.

PMID- 29343991
TI  - Trends and inequities in use of maternal health care services in Indonesia, 1986
      2012.
AB  - Purpose: Overall health status indicators have improved significantly over the
      past three decades in Indonesia. However, the country's maternal mortality ratio
      remains high with a stark inequality by region. Fewer studies have explored
      access inequity in maternal health care service over time using multiple
      inequality markers. In this study, we analyzed Indonesian Demographic and Health
      Survey (DHS) data to explore trends and inequities in use of any antenatal care
      (ANC), four or more ANC (ANC4+), institutional birth, and cesarean section (c
      section) birth in Indonesia during 1986-2012 to inform policy for future
      strategies ending preventable maternal deaths. Methods: Indonesian DHS data from
      1991, 1994, 1997, 2002/3, 2007, and 2012 surveys were downloaded, merged, and
      analyzed. Inequity was measured in terms of variation in use by asset quintile,
      parental education, urban-rural location, religion, and region. Trends in use
      inequities were assessed plotting changes in rich:poor ratio, rich:poor
      difference, and concentration indices over period based on asset quintiles.
      Sociodemographic determinants for service use were explored using multivariable
      logistic regression analysis. Findings: Between 1986 and 2012, institutional
      birth rate increased from 22% to 73% and c-section rate from 2% to 16%. Private
      sector was increasingly contributing in maternal health. There were significant
      access inequities by asset quintile, parental education, area of residence, and
      geographical region. The richest women were 5.45 times (95% CI: 4.75-6.25) more
      likely to give birth in a health facility and 2.83 times (95% CI: 2.23-3.60) more
      likely to give birth by c-section than their poorest counterparts. Urban women
      were 3 times more likely to use institutional birth and 1.45 times more likely to
      give birth by c-section than rural women. Use of all services was higher in Java
      and Bali than in other regions. Access inequity was narrowing over time for use
      of ANC and institutional birth but not for c-section birth. Conclusion: Ongoing
      pro-poor health-financing strategies should be strengthened with introduction of
      innovative ways to monitor access, equity, and quality of care in maternal
      health.

PMID- 29343992
TI  - Validation of BP devices QardioArm(r) in the general population and Omron M6
      Comfort(r) in type II diabetic patients according to the European Society of
      Hypertension International Protocol (ESH-IP).
AB  - Background: Following the European Society of Hypertension International Protocol
      (ESH-IP) Revision 2010, QardioArm(r) and Omron M6 Comfort IT(r) oscillometric
      devices were evaluated in the general population and in patients with type II
      diabetes, respectively, for self-blood pressure (BP) measurement. Methods: Both
      devices, QardioArm(r) and Omron M6 Comfort(r), measure BP at the brachial level.
      The ESH-IP Revision 2010 includes a total number of 33 subjects. For each
      measure, the difference between observer and device BP values was calculated. In
      all, 99 pairs of BP differences are classified into three categories (<=5, <=10,
      and <=15 mmHg). The protocol procedures were followed precisely. Results:
      QardioArm(r) and Omron M6 Comfort(r) fulfilled the requirements of the ESH-IP and
      passed the validation process successfully. For QardioArm(r), a total of 69 out
      of 99 comparisons for systolic blood pressure (SBP) showed an absolute difference
      within 5 mmHg and 82 out of 99 for diastolic blood pressure (DBP). As for Omron
      M6 Comfort(r), a total of 83 out of 99 comparisons for SBP showed an absolute
      difference within 5 mmHg and 77 out of 99 for DBP. The mean differences between
      the device and mercury readings were 0.7+/-5.9 mmHg for SBP and 0.3+/-4.1 mmHg
      for DBP for QardioArm(r) and -1.4+/-4.7 mmHg for SBP and -2.1+/-4.3 mmHg for DBP
      for Omron M6 Comfort(r). With regard to part 2 of ESH-IP 2010, 27 out of 33
      subjects had a minimum of two out of three measurements within 5 mmHg difference
      for SBP and 31 out of 33 subjects for DBP for the QardioArm(r), and 29 out of 33
      patients had a minimum of two out of three measurements within 5 mmHg difference
      for SBP and 26 out of 33 patients for DBP for Omron M6 Comfort(r). Conclusion:
      QardioArm(r) and Omron M6 Comfort(r) readings differing from the mercury standard
      by <5, 10, and 15 mmHg fulfill the ESH-IP Revision 2010 requirements.
      Consequently, these two devices are suitable for use in the general population
      and non-insulin-dependent type II diabetic patients, respectively.

PMID- 29343993
TI  - Management of disseminated intravascular coagulation: current insights on
      antithrombin and thrombomodulin treatments.
AB  - Sepsis and septic shock are frequently complicated by disseminated intravascular
      coagulation (DIC), which decreases the survival rate of patients with sepsis. In
      the past, large international randomized controlled trials (RCTs) using
      physiological anticoagulants for sepsis-induced DIC were not performed; however,
      RCTs have been conducted for sepsis and/or septic shock. In these trials,
      physiological anticoagulants did not show any beneficial effects compared with
      placebo for the treatment of sepsis and/or septic shock. In Japan, DIC treatments
      using antithrombin (AT) and/or recombinant human soluble thrombomodulin (rhTM)
      are common for patients with sepsis-induced DIC. Recently, large propensity score
      analyses demonstrated that AT and rhTM improved survival in patients with sepsis
      induced DIC. Furthermore, post hoc analyses and meta-analyses that selected
      patients with sepsis-induced DIC from the previous large international RCTs
      indicated that physiological anticoagulants improved survival without increasing
      the associated sepsis-induced DIC bleeding. DIC treatments, such as AT and rhTM,
      may demonstrate beneficial effects when they are targeted at patients with sepsis
      induced DIC only.

PMID- 29343994
TI  - Calibration and validation of an item bank for measuring general physical
      function of patients in medical rehabilitation settings.
AB  - Objective: The objective of this study was to report the item response theory
      (IRT) calibration of an 18-item bank to measure general physical function (GPF)
      in a wide range of conditions and evaluate the validity of the derived scores.
      Methods: All 18 items were administered to a large sample of patients (n=2337)
      who responded to the items in the context of their outpatient rehabilitation
      care. The responses, collected 1997- 2000, were modeled using the graded response
      model, an IRT model appropriate for items with two or more response options.
      Inter-item consistency was evaluated based on Cronbach's alpha and item to total
      correlations. Validity of scores was evaluated based on known-groups comparisons
      (age, number of health problems, symptom severity). The strength of a single,
      general factor was evaluated using a bi-factor model. Results were used to
      evaluate IRT assumption and as an indicator of construct validity. Local
      independence of item responses was also evaluated. Results: Response data met the
      assumptions of unidimensionality and local independence. Explained common
      variance of a single general factor was 0.88 (omega hierarchical =0.86). Only two
      of the 153 pairs of item residuals were flagged for local dependence. Inter-item
      consistency was high (0.93) as were item to total correlations (mean =0.61).
      Substantial variation was found in both IRT location (difficulty) and
      discrimination parameters. All omnibus known-groups comparisons were
      statistically significant (p<0.001). Conclusion: Item responses fit the IRT
      unidimensionality assumptions and were internally consistent. The usefulness of
      GPF scores in discriminating among patients with different levels of physical
      function was confirmed. Future studies should evaluate the validity of GPF scores
      based on an adaptive administration of items.

PMID- 29343995
TI  - HumanMethylation450K Array-Identified Biomarkers Predict Tumour
      Recurrence/Progression at Initial Diagnosis of High-risk Non-muscle Invasive
      Bladder Cancer.
AB  - Background: High-risk non-muscle invasive bladder cancer (HR-NMIBC) is a
      clinically unpredictable disease. Despite clinical risk estimation tools, many
      patients are undertreated with intra-vesical therapies alone, whereas others may
      be over-treated with early radical surgery. Molecular biomarkers, particularly
      DNA methylation, have been reported as predictive of tumour/patient outcomes in
      numerous solid organ and haematologic malignancies; however, there are few
      reports in HR-NMIBC and none using genome-wide array assessment. We therefore
      sought to identify novel DNA methylation markers of HR-NMIBC clinical outcomes
      that might predict tumour behaviour at initial diagnosis and help guide patient
      management. Patients and methods: A total of 21 primary initial diagnosis HR
      NMIBC tumours were analysed by Illumina HumanMethylation450 BeadChip arrays and
      subsequently bisulphite Pyrosequencing. In all, 7 had not recurred at 1 year
      after resection and 14 had recurred and/or progressed despite intra-vesical BCG.
      A further independent cohort of 32 HR-NMIBC tumours (17 no recurrence and 15
      recurrence and/or progression despite BCG) were also assessed by bisulphite
      Pyrosequencing. Results: Array analyses identified 206 CpG loci that segregated
      non-recurrent HR-NMIBC tumours from clinically more aggressive
      recurrence/progression tumours. Hypermethylation of CpG cg11850659 and
      hypomethylation of CpG cg01149192 in combination predicted HR-NMIBC recurrence
      and/or progression within 1 year of diagnosis with 83% sensitivity, 79%
      specificity, and 83% positive and 79% negative predictive values. Conclusions:
      This is the first genome-wide DNA methylation analysis of a unique HR-NMIBC
      tumour cohort encompassing known 1-year clinical outcomes. Our analyses
      identified potential novel epigenetic markers that could help guide individual
      patient management in this clinically unpredictable disease.

PMID- 29343996
TI  - Does HLA-B27 Status Influence Ankylosing Spondylitis Phenotype?
AB  - The association of HLA-B27 with ankylosing spondylitis (AS) remains as one of the
      intriguing models that could exist between a molecule and human disease in
      medicine. Although it was reported in 1973, its contribution to AS and related
      spondyloarthritis continues to be a major challenge for scientific community. It
      is important to understand its etiopathogenic mechanism and its functions in
      these diseases. Although the diagnostic and prognostic roles of HLA-B27 in AS are
      still debated, there is an increasing interest for HLA-B27-based effects
      especially in HLA-B27(+) patients with AS. This review will focus in the
      examination of published reports regarding the influence of HLA-B27 status on the
      demographic and clinical features in AS, with specific interest to its role on AS
      severity.

PMID- 29343997
TI  - Hospitalisation in Patients With Heart Failure With Preserved Ejection Fraction.
AB  - Heart failure is highly prevalent with more than 50% of cases being patients with
      a preserved ejection fraction (HFPEF), a figure that is projected to increase due
      to the changing risk factor landscape, in particular the ageing population.
      Overall mortality is similar to patients with heart failure with reduced ejection
      fraction (HFREF), as are the rates of hospitalisation. Patients with HFPEF have
      more comorbid conditions with fewer therapeutic options available. In this
      review, we explore the epidemiology of hospitalisation of HFPEF, the impact of
      current treatment modalities, and the potential of future therapies.

PMID- 29343998
TI  - Rationale and Design for a Monocentric Prospective Study: Sleep Apnea Diagnosis
      Using a Novel Pacemaker Algorithm and Link With Aldosterone Plasma Level in
      Patients Presenting With Diastolic Dysfunction (SAPAAD Study).
AB  - Previous studies showed good agreement between pacemaker respiratory disturbance
      index (RDI) and polysomnography for diagnosis of severe sleep apnea (SA). The aim
      of this study is to investigate the diagnostic accuracy of RDI compared with
      apnea-hypopnea index (AHI) from a cardiorespiratory sleep study for the diagnosis
      of severe SA within patients requiring a pacemaker and meeting diastolic
      dysfunction criteria. Secondary objectives are as follows: correlation between
      plasma aldosterone level and SA severity, diagnostic accuracy of RDI for moderate
      SA, prevalence of SA among patients with diastolic dysfunction, occurrence of
      arrhythmias, and improvement of RDI with continuous positive airway pressure
      therapy. We designed a monocentric prospective nonrandomized study of prevalent
      cases to include 68 patients with a 6-month follow-up. Both RDI and AHI will be
      compared 2 months after implantation and after 1 month of continuous positive
      airway pressure treatment in patients with severe SA. This is the first study
      that examines diagnostic accuracy of pacemaker algorithm for the diagnosis of SA
      and correlation with plasma aldosterone levels in patients with diastolic
      dysfunction. Protocol version: V04. 04/04/2017 Trial registration:
      ClinicalTrials.gov NCT02751021.

PMID- 29343999
TI  - Targeted Treatment With Radio Frequency Ablation for Lingual Tonsil.
AB  - Objectives: Benign enlargement of the lingual tonsils due to various causes may
      cause symptoms that warrant treatment. Conventional lingual tonsillectomy remains
      a challenging procedure, and there is no established standard procedure. We aimed
      to review the patients receiving different methods of lingual tonsil surgery for
      various indications at our institute. Methods: Retrospective clinical data on all
      patients with an ablative operation of the tongue base during the 8-year period
      between 2007 and 2014 at the Helsinki University Hospital, Helsinki, Finland,
      were reviewed. The larger cohort comprised 35 patients, of whom 26 were men
      (74%). Ten patients had undergone solely lingual tonsil radio frequency ablation
      (LTRFA). The minimum follow-up time for all patients was 2 years. Results: Of the
      10 patients, 5 patients with LTRFA had been operated on because of symptomatic
      lingual tonsil hypertrophy and 5 because of periodic fever associated with
      possible lingual tonsil involvement. In 2 of the 5 patients with periodic fever,
      the fever cycles ended after the operation. Of the 5 patients, 3 patients with
      symptomatic lingual tonsil hypertrophy have been non-symptomatic after 1 to 3
      treatment sessions. The last 2 patients continue to have persistent symptoms.
      There were no major complications. Conclusions: Development of new approaches for
      the management of various lingual tonsil conditions is warranted. Lingual tonsil
      volume reduction by LTRFA seems to be a treatment alternative with low morbidity
      but with limited curative effect only.

PMID- 29344000
TI  - Visible-Near Infrared Spectroscopic Assessment of Urogenital Tissue in
      Premenopausal and Postmenopausal Women.
AB  - Background: A clinical study was conducted to evaluate the feasibility of using
      visible and near-infrared (NIR) spectroscopy as a potential noninvasive measure
      of genital skin health in premenopausal and postmenopausal women. Methods: A
      total of 45 female subjects (aged 21-70 years), all of whom gave fully informed
      consent to participate, were enrolled in the study and assigned to 1 of 3 groups:
      15 premenopausal (Pre-M), 15 postmenopausal receiving hormone replacement therapy
      (Post-M HRT), and 15 postmenopausal receiving no form of hormone replacement
      therapy (Post-M non-HRT). Spectral measurements were taken at the vaginal mucosa,
      and spectral data were evaluated for the erythema index (EI), hemoglobin index
      (HI), bilirubin/beta-carotene, and melanin. The color index (CI; calculated as
      the ratio of absorbance at 480 nm/540 nm) was also determined. Results were
      compared with previously published results on biomarkers and physical
      characteristic of genital tissue measured on the same groups of women. Results:
      Spectral measurements from the Post-M Non-HRT subjects indicated a significant
      reduction in HI compared with the Pre-M group (P = .0003) and to the Post-M HRT
      group (P < .0001). Similarly, EI was reduced in the Post-M Non-HRT (P < .0001 and
      P = .0041 for the Pre-M and Post-M HRT groups, respectively). In contrast, the
      Post-M Non-HRT subjects exhibited a significant increase in beta-carotene
      compared with the Pre-M subjects (P = .0098). Bilirubin and melanin were not
      significantly affected. The Post-M Non-HRT group exhibited a significant increase
      in CI, indicating a shift away from the hemoglobin absorption region (510-620 nm
      wavelength) and toward the bilirubin/beta-carotene absorption region (450-490 nm
      wavelength). This change was significant when compared with both the Pre-M group
      (P < .0001) and the Post-M HRT group (P = .0048). The changes in spectral
      measurements were consistent with previously reported changes in physical
      parameters (vaginal atrophy, increased pH, decreased skin temperature) and with
      decreased concentrations of the biomarkers histamine and histidine. Conclusions:
      Hemodynamic spectral characteristics differ in postmenopausal vaginal tissue
      compared with tissue in premenopausal women, with decreased absorbance in the
      hemoglobin absorption region (510-620 nm wavelength) and an increased absorbance
      in the bilirubin/beta-carotene absorption region (450-490 nm wavelength). A
      change in absorbance in the visible and NIR wavelengths is a promising,
      additional measure of genital skin health related to menopause and vulvovaginal
      atrophy.

PMID- 29344001
TI  - Intraventricular Hemorrhage Due to Coagulopathy After Vitamin K Administration in
      a Preterm Infant With Maternal Crohn Disease.
AB  - Intraventricular hemorrhage (IVH) is a devastating morbidity in preterm infants
      and can result in poor neurodevelopmental outcomes. Intraventricular hemorrhage
      usually occurs within 72 hours after birth; post-acute-phase IVH (>1 week after
      birth) is uncommon. Development of the hemostatic system in fetuses and neonates
      is an age-dependent evolving process, and the neonatal hemostatic system is
      characterized by low levels of vitamin K-dependent factors, with further
      reduction caused by prematurity. Importantly, a severe coagulation deficiency can
      be a major contributing factor of IVH. Active maternal Crohn disease (CD) during
      pregnancy causes malnutrition via enteral malabsorption; this may include vitamin
      K deficiency, resulting in fetal vitamin K deficiency. We herein describe a
      preterm infant who was born to a mother with CD and developed post-acute-phase
      IVH due to coagulopathy despite vitamin K administration.

PMID- 29344002
TI  - The journey from clinician to undergraduate medical educator involves four
      patterns of transformation.
AB  - Objectives: Traditionally, teaching is part of a clinician's job. Some
      practitioners recognize the teaching activity as rewarding. This study explored
      the ways clinical practitioners experience their journey from clinicians to
      medical teachers, analyzing their prior experiences of teaching and learning,
      conceptions of good teaching and learning, perceptions of learning environments,
      and finally, how those factors influence their approaches to teaching. Methods:
      Data for phenomenographic analysis were collected through semi-structured
      interviews conducted in Spanish and administered to twelve clinical teachers in
      three medical schools in Colombia. Results: Through sequential phases of
      analysis, we constructed a conceptual diagram to identify critical concepts,
      themes, and categories that describe patterns that clinicians adopt during their
      journey to become medical teachers. We identified two themes and four patterns
      that describe the journey from practitioner to medical teacher: the identity
      theme, referring to "what" practitioners showed as the object of the journey and
      the changing process theme referring to "how" participants adopt changes during
      the journey. We describe four patterns that describe the journey that physicians
      adopt when exposed to the experience of clinical teaching. Conclusion: It is
      possible to identify two themes and to devise at least four patterns in ways of
      experiencing the journey to medical teacher. These patterns are not a fixed set
      of characteristics, but rather a spectrum of experiences. Taking into
      consideration the professional identity of clinical teachers and the path of
      their teaching process change, it might be possible to devise better strategies
      for teaching development activities.

PMID- 29344003
TI  - A medical student in private practice for a 1-month clerkship: a qualitative
      exploration of the challenges for primary care clinical teachers.
AB  - Purpose: The predicted shortage of primary care physicians emphasizes the need to
      increase the family medicine workforce. Therefore, Swiss universities develop
      clerkships in primary care physicians' private practices. The objective of this
      research was to explore the challenges, the stakes, and the difficulties of
      clinical teachers who supervised final year medical students in their primary
      care private practice during a 1-month pilot clerkship in Geneva. Methods: Data
      were collected via a focus group using a semistructured interview guide.
      Participants were asked about their role as a supervisor and their difficulties
      and positive experiences. The text of the focus group was transcribed and
      analyzed qualitatively, with a deductive and inductive approach. Results: The
      results show the nature of pressures felt by clinical teachers. First,
      participants experienced the difficulty of having dual roles: the more familiar
      one of clinician, and the new challenging one of teacher. Second, they felt
      compelled to fill the gap between the academic context and the private practice
      context. Clinical teachers were surprised by the extent of the adaptive load,
      cognitive load, and even the emotional load involved when supervising a trainee
      in their clinical practice. The context of this rotation demonstrated its utility
      and its relevance, because it allowed the students to improve their knowledge
      about the outpatient setting and to develop their professional autonomy and their
      maturity by taking on more clinical responsibilities. Conclusion: These findings
      show that future training programs will have to address the needs of clinical
      teachers as well as bridge the gap between students' academic training and the
      skills needed for outpatient care. Professionalizing the role of clinical
      teachers should contribute to reaching these goals.

PMID- 29344004
TI  - Perceived organizational support and moral distress among nurses.
AB  - Background: Moral distress is prevalent in the health care environment at
      different levels. Nurses in all roles and positions are exposed to ethically
      challenging conditions. Development of supportive climates in organizations may
      drive nurses towards coping moral distress and other related factors. This study
      aimed at determining the level of perceived organizational support and moral
      distress among nurses and investigating the relationship between the two
      variables. Methods: This was a correlational-descriptive study. A total of 120
      nurses were selected using random quota sampling method. A demographic
      questionnaire, Survey of Perceived Organizational Support, and Moral Distress
      Scale were used to collect the data which were analyzed using descriptive and
      analytical tests in SPSS20. Results: The mean perceived organizational support
      was low (2.63 +/- 0.79). The mean moral distress was 2.19 +/- 0.58, which shows a
      high level of moral distress. Moreover, Statistical analysis showed no
      significant relationship between perceived organizational support and moral
      distress (r = 0.01, p = 0.86). Conclusion: Given the low level of perceived
      organizational support and high moral distress among nurses in this study, it is
      necessary to provide a supportive environment in hospitals and to consider
      strategies for diminishing moral distress.

PMID- 29344005
TI  - Biological clocks: their relevance to immune-allergic diseases.
AB  - The 2017 Nobel Prize for Physiology or Medicine, awarded for the discoveries made
      in the past 15 years on the genetic and molecular mechanisms regulating many
      physiological functions, has renewed the attention to the importance of circadian
      rhythms. These originate from a central pacemaker in the suprachiasmatic nucleus
      in the brain, photoentrained via direct connection with melanopsin containing,
      intrinsically light-sensitive retinal ganglion cells, and it projects to
      periphery, thus creating an inner circadian rhythm. This regulates several
      activities, including sleep, feeding times, energy metabolism, endocrine and
      immune functions. Disturbances of these rhythms, mainly of wake/sleep, hormonal
      secretion and feeding, cause decrease in quality of life, as well as being
      involved in development of obesity, metabolic syndrome and neuropsychiatric
      disorders. Most immunological functions, from leukocyte numbers, activity and
      cytokine secretion undergo circadian variations, which might affect
      susceptibility to infections. The intensity of symptoms and disease severity show
      a 24 h pattern in many immunological and allergic diseases, including rheumatoid
      arthritis, bronchial asthma, atopic eczema and chronic urticaria. This is
      accompanied by altered sleep duration and quality, a major determinant of quality
      of life. Shift work and travel through time zones as well as artificial light
      pose new health threats by disrupting the circadian rhythms. Finally, the field
      of chronopharmacology uses these concepts for delivering drugs in synchrony with
      biological rhythms.

PMID- 29344006
TI  - Histone deacetylase 2 (HDAC2) attenuates lipopolysaccharide (LPS)-induced
      inflammation by regulating PAI-1 expression.
AB  - Background: Sepsis is a life-threatening organ dysfunction caused by dysregulated
      host response to infection, and is primarily characterized by an uncontrolled
      systemic inflammatory response. In the present study, we developed an effective
      adjunct therapy mediated by a novel mechanism, to attenuate overt inflammation.
      LPS-treated macrophages were adopted as an in vitro model of endotoxin-induced
      inflammation during sepsis. Experiments were carried out using primary mouse
      peritoneal macrophages and the murine macrophage cell line RAW264.7, to elucidate
      the mechanisms by which HDAC2 modulates endotoxin-induced inflammation. Results:
      Results revealed that PAI-1, TNF, and MIP-2 expression were inhibited by
      theophylline, an HDAC2 enhancer, in a RAW macrophage cell line, following LPS
      induced inflammation. Thus, HDAC2 plays an important role in immune defense by
      regulating the expression of inflammatory genes via the c-Jun/PAI-1 pathway.
      During LPS-induced inflammation, overexpression of HDAC2 was found to inhibit PAI
      1, TNF, and MIP-2 expression. Following LPS stimulation, HDAC2 knockdown
      increased nuclear translocation and DNA binding of c-Jun to the PAI-1 gene
      promoter, thereby activating PAI-1 gene transcription. Furthermore, inhibition of
      PAI-1 by TM5275 alone or in combination with theophylline notably suppressed TNF
      and MIP-2 expression. Conclusion: HDAC2 can attenuate lipopolysaccharide-induced
      inflammation by regulating c-Jun and PAI-1 expression in macrophages.

PMID- 29344007
TI  - Four-factor prothrombin complex concentrate improves thrombin generation and
      prothrombin time in patients with bleeding complications related to rivaroxaban:
      a single-center pilot trial.
AB  - Background: Direct oral anticoagulants (DOACs) pose a great challenge for
      physicians in life-threatening bleeding events. The aim of this study was to test
      the efficacy of reversing the DOAC rivaroxaban using four-factor PCC (prothrombin
      complex concentrate), a non-specific reversing agent. Methods: Patients with life
      threatening bleeding events during rivaroxaban treatment were included and
      administered 25 U kg-1 of PCC. Blood samples were collected immediately prior to
      as well as after PCC treatment at predefined time intervals. The primary endpoint
      was defined as the difference in thrombin generation (TG) parameters ETP
      (endogenous thrombin potential) and Cmax (peak thrombin generation) prior to and
      ten minutes subsequent to PCC treatment. Results: Thirteen patients, of whom the
      majority suffered from intra-cranial haemorrhage (ICH) or subdural haemorrhage
      (SDH), were included and administered PCC. The results show that the ETP (TG)
      significantly (p = 0.001) improved by 68% and Cmax (TG) by 54% (p = 0.001) during
      PCC treatment. In addition, the Quick value (prothrombin time: QuickPT)
      significantly improved by 28% and the activated partial thromboplastin time
      (aPTT) was decreased by 7% ten minutes after PCC administration. Cmax was reduced
      at baseline, but not ETP, aPTT or QuickPT. Lag time until initiation (TG, tlag),
      thromboelastometry clotting time (CTEXTEM) and time to peak (TG, tmax) correlated
      best with measured rivaroxaban levels and were out of normal ranges at baseline,
      but did not improve after PCC administration. In 77% of the patients bleeding
      (ICH/SDH-progression) ceased following PCC administration. During the study three
      participants passed away due to other complications not related to PCC treatment.
      The possibility of thrombosis formation was also evaluated seven days after
      administering PCC and no thromboses were found. Conclusions: This study shows
      that use of PCC improved ETP, Cmax, QuickPT and aPTT. However, of these
      parameters, only Cmax was reduced at the defined baseline. It can be concluded
      that CTEXTEM, tlag and tmax correlated best with the measured rivaroxaban levels.
      The study drug was found to be safe. Nonetheless, additional studies specifically
      targeting assessment of clinical endpoints should be performed to further confirm
      these findings. Clinical trial registration: EudraCT trial No. 2013-004484-31.

PMID- 29344010
TI  - Evidence Supporting No Dose Response of Mortality to Air Quality.

PMID- 29344008
TI  - Understanding the factors that effect maximal fat oxidation.
AB  - Lipids as a fuel source for energy supply during submaximal exercise originate
      from subcutaneous adipose tissue derived fatty acids (FA), intramuscular
      triacylglycerides (IMTG), cholesterol and dietary fat. These sources of fat
      contribute to fatty acid oxidation (FAox) in various ways. The regulation and
      utilization of FAs in a maximal capacity occur primarily at exercise intensities
      between 45 and 65% VO2max, is known as maximal fat oxidation (MFO), and is
      measured in g/min. Fatty acid oxidation occurs during submaximal exercise
      intensities, but is also complimentary to carbohydrate oxidation (CHOox). Due to
      limitations within FA transport across the cell and mitochondrial membranes, FAox
      is limited at higher exercise intensities. The point at which FAox reaches
      maximum and begins to decline is referred to as the crossover point. Exercise
      intensities that exceed the crossover point (~65% VO2max) utilize CHO as the
      predominant fuel source for energy supply. Training status, exercise intensity,
      exercise duration, sex differences, and nutrition have all been shown to affect
      cellular expression responsible for FAox rate. Each stimulus affects the process
      of FAox differently, resulting in specific adaptions that influence endurance
      exercise performance. Endurance training, specifically long duration (>2 h)
      facilitate adaptations that alter both the origin of FAs and FAox rate.
      Additionally, the influence of sex and nutrition on FAox are discussed. Finally,
      the role of FAox in the improvement of performance during endurance training is
      discussed.

PMID- 29344012
TI  - Coding of Tissue and Cell Products.

PMID- 29344009
TI  - Evaluation of nipple aspirate fluid as a diagnostic tool for early detection of
      breast cancer.
AB  - There has been tremendous progress in detection of breast cancer in
      postmenopausal women, resulting in two-thirds of women surviving more than 20
      years after treatment. However, breast cancer remains the leading cause of cancer
      related deaths in premenopausal women. Breast cancer is increasing in younger
      women due to changes in life-style as well as those at high risk as carriers of
      mutations in high-penetrance genes. Premenopausal women with breast cancer are
      more likely to be diagnosed with aggressive tumours and therefore have a lower
      survival rate. Mammography plays an important role in detecting breast cancer in
      postmenopausal women, but is considerably less sensitive in younger women.
      Imaging techniques, such as contrast-enhanced MRI improve sensitivity, but as
      with all imaging approaches, cannot differentiate between benign and malignant
      growths. Hence, current well-established detection methods are falling short of
      providing adequate safety, convenience, sensitivity and specificity for
      premenopausal women on a global level, necessitating the exploration of new
      methods. In order to detect and prevent the disease in high risk women as early
      as possible, methods that require more frequent monitoring need to be developed.
      The emergence of "omics" strategies over the last 20 years, enabling the
      characterisation and understanding of breast cancer at the molecular level, are
      providing the potential for long term, longitudinal monitoring of the disease.
      Tissue and serum biomarkers for breast cancer stratification, diagnosis and
      predictive outcome have emerged, but have not successfully translated into
      clinical screening for early detection of the disease. The use of breast-specific
      liquid biopsies, such as nipple aspirate fluid (NAF), a natural secretion
      produced by breast epithelial cells, can be collected non-invasively for
      biomarker profiling. As we move towards an age of active surveillance, home-based
      liquid biopsy collection kits are increasingly being applied and these could
      provide a paradigm shift where NAF biomarker profiling is used for routine breast
      health monitoring. The current status of established and newly emerging imaging
      techniques for early detection of breast cancer and the potential for alternative
      biomarker screening of liquid biopsies, particularly those applied to high-risk,
      premenopausal women, will be reviewed.

PMID- 29344011
TI  - PCB118-Induced Cell Proliferation Mediated by Oxidative Stress and MAPK Signaling
      Pathway in HELF Cells.
AB  - The present study used human lung fibroblast (HELF) cells as a test model to
      evaluate the role of oxidative stress (OS) and extracellular signal-regulated
      kinases 1/2 (ERK1/2) protein in HELF cell proliferation exposed to PCB118.
      Results from 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide
      demonstrated that PCB118 at lower concentrations stimulated proliferation of HELF
      cell and abrogate proliferative effect at higher dose concentrations and in a
      time-dependent manner. Moreover, reactive oxygen species, malondialdehyde (MDA),
      and superoxide dismutase showed a significant increase at higher concentrations
      of PCB118 than the lower concentrations with the passage of time. Antioxidant
      enzymes such as glutathione peroxidase exhibited decreasing trends in dose- and
      time-dependent manner. Lipid peroxidation assay resulted in a significant
      increase in MDA level in PCB118-treated HELF cells compared with controls,
      suggesting that OS plays a key role in PCB118-induced toxicity. Comet assay
      indicated a significant increase in genotoxicity at higher concentrations of
      PCB118 exposure than the lower concentrations. It was found that PCB118 showed
      expression of ERK1/2 protein after 4 hours, while after 48 hours, the protein
      expression was less, indicating PCB toxicity to MAPK protein of HELF cell.
      Oxidative stress, ERK1/2, and HELF cell proliferation exhibited correlation. The
      results will elaborate toxicological evaluation of PCB118 to HELF cells and will
      help to develop drug for PCB-induced diseases.

PMID- 29344013
TI  - ISBT 128 Standard for Coding Medical Products of Human Origin.
AB  - Background: ISBT 128 is an international standard for the terminology, coding,
      labeling, and identification of medical products of human origin (MPHO). Full
      implementation of ISBT 128 improves traceability, transparency, vigilance and
      surveillance, and interoperability. Methods: ICCBBA maintains the ISBT 128
      standard through the activities of a network of expert volunteers, including
      representatives from professional scientific societies, governments and users, to
      standardize and maintain MPHO identification. These individuals are organized
      into Technical Advisory Groups and work within a structured framework as part of
      a quality-controlled standards development process. Results: The extensive
      involvement of international scientific and professional societies in the
      development of the standard has ensured that ISBT 128 has gained widespread
      recognition. The user community has developed confidence in the ability of the
      standard to adapt to new developments in their fields of interest. The standard
      is fully compatible with Single European Code requirements for tissues and cells
      and is utilized by many European tissue establishments. ISBT 128's flexibility
      and robustness has allowed for expansions into subject areas such as cellular
      therapy, regenerative medicine, and tissue banking. Conclusion: ISBT 128 is the
      internationally recognized standard for coding MPHO and has gained widespread use
      globally throughout the past two decades.

PMID- 29344014
TI  - From the EU Legislation to the Application of the Single European Code: Support
      to the Implementation.
AB  - The Italian National Transplant Centre (CNT) is coordinating with the Italian
      National Blood Centre (CNS) the Joint Action '!' (www.eurocet128.eu), already
      built the European Tissue Establishment and Tissue and Cell Product Compendia
      between 2011 and 2014 in order to provide European Member States with a tool
      which would grant traceability of tissues and cells at human transplant purpose
      across the European Union. The two compendia are available on an online platform
      hosted and managed by the European Commission.

PMID- 29344015
TI  - Implementation of the Single European Code in a Multi-Tissue Bank.
AB  - Introduction: The traceability of tissue and cells transplants is important to
      ensure a high level of safety for the recipients. With the final introduction of
      the Single European Code (SEC) in April 2017 in the EU a consistent system among
      all member states became mandatory. Methods: The regulations for the SEC on EU
      and national level were evaluated. An overview on the different parts of the SEC
      with detailed explanations is given. Our own experiences with the implementation
      of the SEC in our multi-tissue bank are reported in addition. Results: The
      implementation of the SEC in our multi-tissue bank could be successfully
      realized. However, it revealed a number of difficulties, especially the sterile
      labeling of certain tissue transplants and the complex update of the existing
      database. Conclusion: The introduction of the SEC has made a contribution to the
      safety of recipients of tissue and cells transplants through a system of
      comprehensive and transparent traceability.

PMID- 29344016
TI  - Coding of Tissue and Cell Preparations Using Eurocode.
AB  - Traceability of products requires their unique identification. In Germany blood
      products have been encoded by Eurocode since 1998. EU Directives 2004/23/EC,
      2006/86/EC and 2015/565/EC demanded unique identification and safe traceability
      procedure also for tissues and cells. Eurocode IBLS e.V. and the German Society
      of Transfusion Medicine and Immunohematology (DGTI) working parties '!' within
      the Single European Code (SEC). Several data elements of Eurocode can be used to
      create the complete SEC data structure, except the tissue establishment number.
      This can be found on the EU Coding Platform in the internet. Consequently,
      existing software and labeling solutions in Eurocode format could be easily
      upgraded with SEC.

PMID- 29344017
TI  - Global Registration Identifier for Donors (GRID) of Hematopoietic Stem Cells:
      Road to Automation and Safety.
AB  - Once a cohort exceeds a certain size, it becomes mandatory to assign an
      identifier (ID) for each individual to ensure a secure, reliable, and unambiguous
      assignment. In the field of hematopoietic stem cell transplantation, with a still
      growing number of voluntary unrelated donors, it was recognized that a system
      needs to be developed to uniquely identify potential donors on a global scale to
      facilitate communication and to prevent errors in identification of donors.
      Efforts in this respect resulted in establishment of the GRID, with a defined
      structure and allocated rules. To successfully implement such a project,
      collaboration among all organizations involved in the process of volunteer donor
      recruitment, facilitation, and provision of hematopoietic stem cell products is
      necessary. Therefore, rapidly accessible information combined with a high level
      of communication and exchange of experiences is crucial. Established systems like
      the ISBT 128 and the Single European Code (SEC), which standardize the
      terminology, identification, coding, and labeling of tissues and cells of human
      origin, serve as a basis on how to successfully implement the GRID on a global
      scale.

PMID- 29344018
TI  - Three-Year Experience in NAT Screening of Blood Donors for Transfusion
      Transmitted Viruses in Croatia.
AB  - Background: Croatia implemented individual donation (ID)-NAT testing of blood
      donors in 2013 for three viruses HBV, HCV, and HIV-1 as a mandatory test for all
      blood donors. This study assessed the impact of NAT screening 3 years after its
      implementation. Methods: A total of 545,463 donations were collected and screened
      for HBV, HCV, and HIV-1 using the Procleix Ultrio Plus Assay. All initially
      reactive (IR) NAT samples were retested in triplicate and, if repeatedly reactive
      (RR), NAT discriminatory assay (dNAT) was performed. ID-NAT positive donations
      were confirmed by RT-PCR on the COBAS AmpliPrep/TaqMan platform. Results: Out of
      545,463 samples tested, 108 (0.02%) were RR in NAT. There were 82 (75,9%) HBV
      reactive, 16 (14.8%) HCV reactive, and 10 (9.3%) HIV-1 reactive samples. 51
      (47.2%) samples were ID-NAT positive only. Out of these 51 NAT yield cases, 1
      window period HIV-1 and 50 occult HBV infections (OBI) were determined. There
      were only two potential HBV DNA transmissions from OBI donors. Conclusion: The
      implementation of NAT screening for three viruses has improved blood safety in
      Croatia. During the 3-year period, 1 window period HIV-1 and a number of occult
      HBV donations were identified.

PMID- 29344019
TI  - Using Blood Donor-Derived ABO and RhD Blood Groups Helps to Detect Wrong Blood in
      Tube Errors in Recipients.
AB  - Background: Comparing the ABO and RhD group of a recipient's current pre
      transfusion sample against their historical group is an important means of
      detecting wrong blood in tube (WBIT) errors. This study investigated the utility
      of using the donor ABO and RhD group as the historical check for recipients.
      Methods: A single database stores serological information on blood donors,
      pregnant women, and patients throughout southern Denmark. A donor ABO and RhD
      group can be the historical blood group should that donor later require a
      transfusion. This database was searched to determine how often the ABO and RhD
      group on a recipient's current pre-transfusion sample was discrepant with their
      historical donor-derived blood group. Results: During about 21 years, ABO and RhD
      groupings were performed on 76,455 blood donors and on 424,697 patients. There
      were 13,630/424,697 (3.2%) patients who had their donor-derived ABO and RhD group
      used as the historical comparison with the current sample; 6/13,630 (0.04%) of
      the current pre-transfusion samples on these patients were discrepant with the
      donor-derived historical group because of WBIT errors. Seven other discrepancies
      with the donor-derived blood group were also found. Conclusion: Accessing the
      donor-derived ABO and RhD group can be an important safeguard against WBIT
      mediated mistransfusions.

PMID- 29344020
TI  - A Case of Immune Thrombocytopenia as a Rare Side Effect of an Immunotherapy with
      PD1-Blocking Agents for Metastatic Melanoma.
AB  - Background: Checkpoint blocking agents such as pembrolizumab or nivolumab may
      induce a diversity of mostly autoimmune-mediated side effects. These autoimmune
      phenomena mainly affect ductless glands such as the pituitary gland
      (hypophysitis), the thyroid gland (thyreoiditis), the skin (vitiligo and rash),
      the colon (colitis), and the lung (pneumonitis). Furthermore, many other organs
      or organ systems may be affected. Case Report: This work describes a case of an
      immune thrombocytopenia that developed or rather became clinically significant
      shortly after initiation of a systemic therapy with first nivolumab and later
      pembrolizumab given due to metastatic melanoma. Platelet counts before this
      systemic therapy were slightly decreased with values around 110/nl (normal value
      140-400/nl). Thrombocytopenia developed or became apparent rapidly within 10 days
      after the first intravenous application of nivolumab and worsened after
      changeover to pembrolizumab. Therapy had to be stopped due to disease progression
      and steady aggravation of thrombocytopenia. Immune hematology assays could prove
      an autoimmune mediated genesis of thrombocytopenia. Conclusion: Checkpoint
      inhibitors may induce a multiplicity of mostly autoimmune-mediated side effects.
      In contrast to chemotherapy-induced cytopenia that results from bone marrow
      toxicity, thrombocytopenia in melanoma patients treated with checkpoint
      inhibiting substances seems to result from autoimmune-mediated side effects in
      the majority of the cases. Thorough laboratory controls during these therapies
      are therefore required. In case of thrombocytopenia, immune hematology testing to
      diagnose or rule out immune thrombocytopenia is indispensable.

PMID- 29344021
TI  - Relevance of Endothelial Cell-Specific Molecule 1 (Endocan) Plasma Levels for
      Predicting Pulmonary Infection after Cardiac Surgery in Chronic Kidney Disease
      Patients: The Endolung Pilot Study.
AB  - Objectives: This pilot study aimed to evaluate the relevance of endocan plasma
      levels for predicting pulmonary infection after cardiac surgery in patients with
      chronic kidney disease (CKD). Methods: Serum collected in a previous prospective
      cohort study (from 166 patients with preoperative CKD who underwent cardiac
      surgery) was used. Five patients with postoperative pulmonary infection were
      compared with 15 randomly selected CKD patients with an uneventful outcome. Blood
      samples were tested at 4 time points (preoperatively and 6, 12, and 24 h after
      the end of surgery). Endocan, procalcitonin, and C-reactive protein plasma levels
      were compared between the two groups. Results: At 6 h, the patients with
      pulmonary infection had significantly higher levels of endocan than the patients
      without pulmonary infection (24.2 +/- 15.6 vs. 6.4 +/- 3.2 ng/mL; p = 0.03). A
      receiver operating characteristic curve analysis showed 80% sensitivity and 100%
      specificity for endocan to predict pulmonary infection (area under the curve
      0.84), with a cutoff value of 15.9 ng/mL. The time saved by assessment of the
      endocan dosage compared to a clinical diagnosis of pulmonary infection was 47 h.
      Conclusion: This pilot study showed that a specific study to assess the link
      between endocan plasma levels and pulmonary infection after cardiac surgery in
      CKD patients is of potential utility.

PMID- 29344022
TI  - Role of Body Mass Index in Acute Kidney Injury Patients after Cardiac Surgery.
AB  - Background/Aims: To explore the association of body mass index (BMI) with the
      risk of developing acute kidney injury after cardiac surgery (CS-AKI) and for AKI
      requiring renal replacement therapy (AKI-RRT) after cardiac surgery. Methods:
      Clinical data of 8,455 patients undergoing cardiac surgery, including demographic
      preoperative, intraoperative, and postoperative data were collected. Patients
      were divided into underweight (BMI <18.5), normal weight (18.5<= BMI <24),
      overweight (24<= BMI <28), and obese (BMI >=28) groups. The influence of BMI on
      CS-AKI incidence, duration of hospital, and intensive care unit (ICU) stays as
      well as AKI-related mortality was analyzed. Results: The mean age of the patients
      was 53.2 +/- 13.9 years. The overall CS-AKI incidence was 33.8% (n = 2,855) with
      a hospital mortality of 5.4% (n = 154). The incidence of AKI-RRT was 5.2% (n =
      148) with a mortality of 54.1% (n = 80). For underweight, normal weight,
      overweight, and obese cardiac surgery patients, the AKI incidences were 29.9,
      31.0, 36.5, and 46.0%, respectively (p < 0.001). The hospital mortality of AKI
      patients in the 4 groups was 9.5, 6.0, 3.8, and 4.3%, whereas the hospital
      mortality of AKI-RRT patients in the 4 groups was 69.2, 60.8, 36.4, and 58.8%,
      both significantly different (p < 0.05). Hospital and ICU stay durations were not
      significantly different in the 4 BMI groups. Conclusion: The hospital prognosis
      of AKI and AKI-RRT patients after cardiac surgery was best when their BMI was in
      the 24-28 range.

PMID- 29344023
TI  - Eicosapentaenoic Acid as a Potential Therapeutic Approach to Reduce
      Cardiovascular Risk in Patients with End-Stage Renal Disease on Hemodialysis: A
      Review.
AB  - Background: Patients with end-stage renal disease on hemodialysis have excess
      cardiovascular disease (CVD) burden with substantially increased CV event rates
      compared with the general population. Summary: Traditional interventions that,
      according to standard clinical guidelines, reduce CV risk such as
      antihypertensive therapy, diet, exercise, and statins are not similarly effective
      in the hemodialysis population. This raises the question of whether additional
      risk factors, such as enhanced inflammation and oxidative stress, may drive the
      increased CVD burden in hemodialysis patients. Eicosapentaenoic acid (EPA), an
      omega-3 polyunsaturated fatty acid, is incorporated into the atherosclerotic
      plaque as well as membrane phospholipid bilayers and produces beneficial effects
      on inflammatory and oxidative mechanisms involved in atherosclerotic plaque
      formation and progression. EPA levels and the ratio of EPA to the omega-6
      polyunsaturated fatty acid arachidonic acid (AA) are reduced in hemodialysis
      patients. Serum EPA levels have been inversely correlated with proinflammatory
      cytokines, and the EPA/AA ratio has been inversely associated with CV events in
      hemodialysis cohorts. Three recent studies involving over 800 hemodialysis
      patients and follow-up of 2-3 years suggest that EPA therapy may improve clinical
      outcomes in this patient population as evidenced by significant reductions in
      cardiovascular mortality, all-cause mortality, and/or CV events. Key Messages:
      Further studies with high-purity EPA are warranted in patients on hemodialysis,
      especially given the fact that other interventions including antihypertensives,
      diet, exercise, and statins have not provided meaningful benefit.

PMID- 29344024
TI  - Elevated Phosphate Levels Trigger Autophagy-Mediated Cellular Apoptosis in H9c2
      Cardiomyoblasts.
AB  - BACKGROUND/AIM: In chronic kidney disease (CKD), kidneys fail to maintain
      phosphorus homeostasis in serum. Elevated phosphorus levels in serum have been
      associated with cardiovascular diseases in CKD patients and in normal
      individuals. In this study, we evaluated the level of autophagy- and apoptosis
      related markers under different concentrations of hyperphosphate in myocardial
      cells. METHODS: Modulation inflicted on the levels of various survival-,
      autophagy-, and apoptosis-related markers were determined by Western blotting
      analysis using total protein extract. FITC-annexin V staining was performed to
      quantify the apoptotic cells in all groups. RESULTS: Hyperphosphate treatments
      showed to induce autophagy-related proteins beclin-1, ATG7, and LC3 II through
      the pAMPK-ULK1 pathway in Western blotting analysis. Further, apoptosis
      associated proteins such as Bax, Bid, cytochrome c, and c-caspase-9 were also
      upregulated with hyperphosphate treatment. 3-Methyladenine, an autophagy
      inhibitor, inhibited apoptosis significantly in FITC-annexin V staining, and the
      inhibition of Bax, cytochrome c, and c-caspase-3 was shown by Western blotting.
      CONCLUSION: The results suggest that hyperphosphate in H9c2 cardiomyoblasts would
      lead to cellular apoptosis via autophagy, which is mediated by the pAMPK
      signaling pathway. Our findings revealed the possible mechanism responsible for
      the heart damage under hyperphosphatemia.

PMID- 29344025
TI  - Insulin Resistance in Kidney Disease: Is There a Distinct Role Separate from That
      of Diabetes or Obesity?
AB  - Insulin resistance is a central component of the metabolic dysregulation observed
      in obesity, which puts one at risk for the development of type 2 diabetes and
      complications related to diabetes such as chronic kidney disease. Insulin
      resistance and compensatory hyperinsulinemia place one at risk for other risk
      factors such as dyslipidemia, hypertension, and proteinuria, e.g., development of
      kidney disease. Our traditional view of insulin actions focuses on insulin
      sensitive tissues such as skeletal muscle, liver, adipose tissue, and the
      pancreas. However, insulin also has distinct actions in kidney tissue that
      regulate growth, hypertrophy, as well as microcirculatory and fibrotic pathways
      which, in turn, impact glomerular filtration, including that governed by
      tubuloglomerular feedback. However, it is often difficult to discern the distinct
      effects of excess circulating insulin and impaired insulin actions, as exist in
      the insulin resistance individual, from the associated effects of obesity or
      elevated systolic blood pressure on the development and progression of kidney
      disease over time. Therefore, we review the experimental and clinical evidence
      for the distinct impact of insulin resistance on kidney function and disease.

PMID- 29344026
TI  - Evaluation of the Predictive Value of the Serum Calcium-Magnesium Ratio for All
      Cause and Cardiovascular Mortality in Incident Dialysis Patients.
AB  - Background/Aim: Cardiovascular disease is the most serious cause of death in
      patients on hemodialysis. Low serum magnesium (Mg) and high serum calcium (Ca)
      levels have been associated with poor outcome and cardiovascular mortality in
      patients on maintenance and initiation dialysis. As a more accurate marker is
      warranted, we evaluated the efficacy of a novel serum Ca-Mg marker of all-cause
      and cardiovascular mortality that indicates vessel calcification. Methods: We
      recruited 378 consecutive patients with end-stage renal disease who started
      dialysis between January 2009 and December 2015 at the Japanese Red Cross
      Ishinomaki Hospital. We collected data of patients' demographic characteristics
      and comorbidities from their electronic medical records. We retrospectively
      examined the association of the serum Ca-Mg ratio with all-cause and
      cardiovascular mortality using the Cox proportional hazard model, and determined
      the value that predicted cardiovascular death using the receiver operating
      characteristic (ROC) curve. Results: Overall, 253 patients with serum Mg and Ca
      data were analyzed. The 3-year survival rate of this group was 0.70 (95%
      confidence interval [CI] 0.55-0.80), and the hazard ratio for the risk of death
      was 3.94 (95% CI 1.37-11.31). The 3-year cardiovascular mortality rate was 0.12
      (95% CI 0.05-0.23), which was significantly higher than that of the other groups.
      The ROC curve of cardiovascular mortality with the Ca-Mg ratio was greater than
      that of Mg (area under the curve 0.75 vs. 0.69, p = 0.037). Conclusion: A high Ca
      Mg ratio was significantly associated with all-cause and cardiovascular
      mortality, and it was more accurate than serum Mg.

PMID- 29344027
TI  - Plasma Volume and Renal Function Predict Six-Month Survival after Hospitalization
      for Acute Decompensated Heart Failure.
AB  - Background: Plasma volume (PV) is contracted in stable patients with heart
      failure (HF) due to decongestion strategies. On the other hand, increased PV can
      adversely affect the trajectory of HF. We therefore examined the effects of
      increased percentage change in PV (%DeltaPV), blood urea nitrogen (BUN), and
      %DeltaPV stratified by BUN and glomerular filtration rate (GFR) on survival after
      discharge in patients hospitalized for acute decompensated HF (ADHF). Methods: We
      used the Strauss-Davis-Rosenbaum formula to calculate the %DeltaPV between
      baseline and hospital discharge in a cohort from the Evaluation Study of
      Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness trial
      (ESCAPE). Kaplan-Meier curves were constructed for survival over 6 months. Cox
      proportional hazards regression was used to obtain adjusted hazard ratios (HR)
      and 95% confidence intervals (95% CI) for the associations between survival after
      discharge and %DeltaPV, BUN, and %DeltaPV stratified by BUN and GFR. Results: Of
      the 324 patients included in our study (age 56.1 +/- 13.6 years, 26.5% female),
      those with increased or no %DeltaPV at discharge were less likely to survive at 6
      months compared with those having reduced %DeltaPV (log rank, p = 0.0093).
      Increased %DeltaPV (HR 1.08 per 10% increase; 95% CI: 1.02-1.14) and increased
      BUN at discharge (HR 1.02 per mg/dL; 95% CI: 1.01-1.03) were independently
      associated with worse survival. Decreasing %DeltaPV had a greater association
      with improved survival in patients with discharge BUN <31 mg/dL (p = 0.02) and
      discharge GFR >40 mL/min/1.73 m2 (p = 0.047). Conclusions: Increased %DeltaPV and
      BUN at discharge predicted worse 6-month survival in patients with ADHF.
      Decreased %DeltaPV with low BUN or high GFR at discharge was associated with
      improved survival.

PMID- 29344028
TI  - Combination Therapy with Renin-Angiotensin System Blockers and Vitamin D Receptor
      Activators for Predialysis Patients Is Associated with the Incidence of
      Cardiovascular Events after Dialysis Initiation: A Multicenter Nonrandomized
      Prospective Cohort Study.
AB  - Background: Several human studies reported that the combined use of renin
      angiotensin system blockers (RASBs) and vitamin D receptor activators (VDRAs)
      resulted in decreased urinary protein excretion. However, it is unknown whether
      this combination therapy influences the incidence of cardiovascular (CV) events
      in dialysis patients. Methods: The study was a multicenter nonrandomized
      prospective cohort analysis including 1,518 patients. Patients were classified
      into 4 groups based on medications prescribed before dialysis initiation: those
      who did not receive RASBs or oral VDRAs (N group), those receiving only RASBs,
      those receiving only VDRAs, and those receiving a combination of RASBs and VDRAs
      (RD group). CV events after dialysis initiation were compared using the log-rank
      test. Factors contributing to the incidence of CV events were examined using
      multivariate Cox proportional hazard regression analysis. Results: Significant
      differences were observed in the incidence of CV events and all-cause mortality
      between the 4 groups (p = 0.021 and p = 0.001, respectively). Cox proportional
      hazard analysis revealed that the incidence of CV events was significantly lower
      in the RD group than in the N group (hazard ratio [HR] = 0.65, 95% confidence
      interval [CI]: 0.50-0.86, p = 0.002). Multivariate analysis revealed that the
      incidence of CV events was significantly lower in the RD group than in the N
      group (HR = 0.66, 95% CI: 0.47-0.93, p = 0.016). Conclusion: Combination therapy
      with RASBs and VDRAs in patients before dialysis initiation was associated with a
      reduction in CV events during maintenance dialysis.

PMID- 29344029
TI  - Primary Adrenal Lymphoma Presenting with Adrenal Failure: A Case Report and
      Review of the Literature.
AB  - Introduction: Primary adrenal lymphoma is rare, with a few cases reported in the
      literature. Most often it manifests as bilateral adrenal lesions and adrenal
      insufficiency is a common complication. Case Presentation: A 53-year-old male was
      referred with abdominal discomfort and darkening of the skin since 1 month prior
      to admission. His workups detected large bilateral adrenal masses. The patient
      was admitted due to hypotension, and was diagnosed with adrenal insufficiency.
      Laboratory studies showed high erythrocyte sedimentation rate (ESR), lactate
      dehydrogenase (LDH), and adrenocorticotropin levels. There was no other organ
      involvement and computed tomography (CT)-guided percutaneous biopsy of the
      adrenal gland revealed B-cell type of non-Hodgkin lymphoma. Replacement therapy
      with glucocorticoid and mineralocorticoid was initiated with remission of
      symptoms. After 3 months of chemotherapy his condition improved, but the patient
      worsened thereafter and died 2 months later. Conclusions: However, this case
      reminded the importance of considering primary adrenal lymphoma in the
      differential diagnosis of bilateral adrenal masses, especially if the patient
      presents with adrenal insufficiency.

PMID- 29344030
TI  - Optimal Cutoff Points for Anthropometric Variables to Predict Insulin Resistance
      in Polycystic Ovary Syndrome.
AB  - Background: Insulin resistance (IR) is a major cardiometabolic risk factor in
      females with polycystic ovary syndrome (PCOS). The euglycemic clamp is the gold
      standard method to measure IR. However, considering the time and cost that it
      takes, surrogate markers of IR are now widely used. The current study aimed at
      evaluating the cutoff points of even less invasive anthropometric and body
      composition variables to predict IR in females with PCOS. Methods: The current
      cross sectional study selected 224 females with PCOS, using Rotterdam criteria,
      referred to reproductive endocrinology research center; 88 of which were
      diagnosed with insulin resistance. Receiver operating characteristics curve was
      used to explore the best cutoff values of each anthropometric and body
      composition measures. IR was defined as homeostasis model assessment formula
      greater or equal to 2.6: HOMA-IR = fasting insulin (mU/L) * fasting plasma
      glucose (mM/L)/22.5. Results: The highest area under the curve (0.751) was for
      the multiplication of waist circumference (WC) by body mass index (BMI), as a
      single index. The highest sensitivity and specificity were for body water (BW)
      percentage (82% for values greater than 32.85%) and WC (79% for values greater
      than 88 cm), respectively. Conclusions: It was concluded that there were simple
      anthropometric variables; e.g., WC * BMI, percentage of BW, and WC that could
      help to estimate IR in clinical settings especially when the gold standard or
      surrogate markers of IR were unavailable.

PMID- 29344031
TI  - Age-Period-Cohort Analysis of Obesity and Overweight in Iranian Children and
      Adolescents.
AB  - Background: To date, few studies looked upon obesity and overweight in children
      and adolescents through the 3 different temporal dimensions of age, period, and
      cohort. The current study aimed at evaluating the trends of these health issues
      among children under 19 years old using the age-period-cohort (APC) analysis.
      Methods: Data gathered through 5 cross sectional studies including 2 national
      health surveillance (1990 - 91 and 1999), and 3 CASPIAN surveys (2003, 2009, and
      2011). Subjects were classified by their body mass index (BMI) into 3 groups of
      normal (BMI < 85th percentile), overweight-obese (85th percentile < BMI < 95th
      percentile), and obese (95th percentile < BMI). Intrinsic estimator method was
      used to analyze the effects of age, period, and birth cohort on obesity and
      overweight among the subjects. Results: A total of 80,698 children and
      adolescents under 19 years old, including 40,419 (50.09%) males and 40,279
      (49.91%) females, were evaluated. The prevalence of obesity decreased
      progressively by age in males and females with minor discrepancies. It increased
      from 1990 to 2009 in both genders, but from that point on remained quite constant
      in males and dropped significantly in females. The prevalence of obesity was
      steady in earlier birth cohorts, but increased significantly after the birth
      cohorts from 1986 to 1990. Conclusions: Environmental factors and social stresses
      during neonatal and infantile periods (birth cohort effect) along with other
      variables influencing the children later in their lives (period effect) affect
      the prevalence of overweight and obesity substantially. Moreover, a decrease in
      the prevalence of obesity and overweight was observed by age increase (age
      effect).

PMID- 29344032
TI  - Neck Circumference Percentiles of Iranian Children and Adolescents: The Weight
      Disorders Survey of CASPIAN IV Study.
AB  - Background: Neck circumference (NC), emerging as a key morphological index for
      pediatric obesity, is associated with obesity- and overweight-related detrimental
      conditions in children. In this study, we aimed to provide the age- and sex
      specific percentile reference values for neck circumference of the Iranian
      children and adolescents. Methods: We used the data gathered through the weight
      disorders survey of CASPIAN IV study conducted in 2011 - 2012 in Iran, including
      a total of 21954 Iranian children and adolescents, composed of 10750 girls and
      11204 boys, aged 7 - 18 years old. We presented the interval of NC percentile in
      three age groups of 7 - 10 years, 11 - 14 years, and 15 - 18 years. Finally, age
      specific nomograms of NC for both genders in the Iranian and Canadian populations
      were compared. Results: The intervals of 90th percentile of NC for boys in the
      three periods of school age (7 - 10 years), pre-adolescence (11 - 14 years), and
      adolescence (15 - 18 years) were 24.2 - 30.0 cm, 26.6 - 33.2 cm, and 30.1 - 38.5
      cm, respectively. These intervals for girls were 23.7 - 30.1 cm, 26.5 - 33.7 cm,
      and 28.5 - 36.0 cm, respectively. NC increased with age in both boys and girls
      and its variability showed an increasing trend with age. Conclusions: We
      demonstrated for the first time the NC reference values for the Iranian children
      and adolescents aged 7 - 18 years old. Considering the significant differences
      between our national NC references and the values reported from the Canadian
      population, it seems logical to use these national percentiles not only for
      epidemiologic studies but also for routine clinical examinations.

PMID- 29344033
TI  - Investigating the Prevalence of Low Bone Mass in Children of Southern Iran and
      Its Associated Factors.
AB  - Background: Improving peak bone mass and bone strength in the first years of life
      and enhancing it during young adulthood could prevent osteoporosis and fractures
      in the last years of life. We evaluated the prevalence of low bone mass in the
      lumbar and femoral neck and its associated factors in southern Iranian children.
      Methods: This is a cross-sectional study on healthy Iranian children aged 9 - 18
      years old during 2011 - 2012. Dual energy X-ray absorptiometry (DEXA) was used
      for measuring bone mineral density (BMD). BMD Z-score <= -2 was considered as
      low. Anthropometric data, physical activity, sun exposure, puberty, and mineral
      biochemical parameters were assessed. Data were analyzed using SPSS v.15.
      Results: 477 normal children, including 236 (49.5%) girls and 241 (50.5%) boys,
      aged 13.8 +/- 2.7 years were enrolled. Prevalence of low bone mass (LBM) in the
      femoral and lumbar region was 10.7% and 18.7%, respectively. The prevalence of
      LBM in femur of girls is twice more than boys. Fat mass index, BMI Z-score, and
      physical activity were associated with lumbar low bone mass. BMI Z-score and
      physical activity were associated with femoral low bone mass. Conclusions: High
      prevalence of low bone mineral density in children 9 to 18 years in south of the
      country is concerned and is needed to plan for prevention and treatment. BMI-Z
      score, fat mass index, and physical activity were the 3 most important preventive
      factors in developing low bone mass in children.

PMID- 29344034
TI  - Socio-Demographic Determinants of Health-Related Quality of Life in Tehran Lipid
      and Glucose Study (TLGS).
AB  - Background: Health-related quality of life (HRQOL) is a multi-dimensional concept
      that is affected by different variables. A large body of evidence shows that
      socio-demographic factors have a significant influence on HRQOL. When considering
      differences in cultural contexts and social values of various countries and the
      lack of evidence regarding socio-demographic determinants of HRQOL among the
      Iranian general population, it is important to verify the main socio-demographic
      determinants of HRQOL in an urban Iranian population. Objectives: This study
      aimed to explore socio-demographic factors associated with HRQOL and to ascertain
      the determinants of poor HRQOL in participants of the Tehran lipid and glucose
      study (TLGS). Methods: The participants included 3491 adults, aged >= 20 years,
      who had participated in the TLGS. To obtain socio-demographic and HRQOL
      information, participants were interviewed by trained interviewers. Mean HRQOL
      scores were compared using the student's t test and analysis of variance (ANOVA).
      To determine significant determinants of poor HRQOL, multivariate logistic
      regression analysis was performed. Results: Mean ages of males and females were
      47.7 +/- 15.6 and 47.8 +/- 14.2 years, respectively and 58.6% of participants
      were male. Males had significantly higher scores compared to females in both the
      physical and mental domains of HRQOL (P < 0.001). In males, significant
      determinants of poor physical HRQOL were older age, being married, being
      unemployed yet having other sources of income, having literacy levels below high
      school diploma, and having chronic diseases (P < 0.05). In females, however older
      age and being housewives were significant determinants of poor physical HRQOL (P
      < 0.05). In addition, significant determinants of poor mental HRQOL were younger
      age and being single or divorced/widowed in males and younger age and being
      illiterate as well as having literacy levels below high school diploma in females
      (P < 0.05). Conclusions: Current findings highlight the importance of socio
      demographic determinants of HRQOL in both genders, specifically in the physical
      domain, and demonstrate their roles to be more prominent in males. These findings
      highlight gender-specific associations between socio-demographic factors and
      various aspects of HRQOL among the TLGS population, which could be applied in
      future research focusing on non-communicable diseases and planning health
      promotion programs.

PMID- 29344035
TI  - Hypercalcaemic Pancreatitis, Adrenal Insufficiency, Autoimmune Thyroiditis and
      Diabetes Mellitus in a girl with Probable Sarcoidosis.
AB  - Introduction: Sarcoidosis is a multisystemic granulomatous disease with diverse
      and often non-specific symptoms during childhood. The clinical manifestations
      sometimes include endocrinopathies related to sarcoid infiltration of various
      endocrine organs, but more commonly due to the associated autoimmune endocrine
      disorders. There are only a few reports of multiple autoimmune and non-autoimmune
      endocrine problems occurring simultaneously in patients with sarcoidosis. We
      report a girl with probable sarcoidosis who also had Hashimoto's thyroiditis,
      Type 1 diabetes (T1D) and secondary adrenal insufficiency. Case Presentation: A 9
      year-old girl previously diagnosed with autoimmune hypothyroidism and vitamin D
      deficiency, presented with hypercalcemic pancreatitis after initiating vitamin D
      supplementation that lead to a diagnosis of probable sarcoidosis. Secondary
      adrenal insufficiency and T1D were subsequently diagnosed. Her angiotensin
      converting enzyme levels on 2 occasions were 106 and 135 nmol/mL/min (normal
      range 10 - 43). All investigations conducted to exclude several infectious and
      malignant conditions that may mimic sarcoidosis were negative. The patient showed
      a good response to treatment with hydrocortisone, levothyroxine, insulin and
      methotrexate. Conclusions: To our knowledge, ours is the youngest ever patient
      reported in the literature with sarcoidosis to develop multiple autoimmune and
      non-autoimmune endocrinopathies.

PMID- 29344037
TI  - The Effects of Ginger on Fasting Blood Sugar, Hemoglobin A1c, and Lipid Profiles
      in Patients with Type 2 Diabetes.
AB  - Background: Lipid and glycemic abnormalities are prevalent in diabetes leading to
      long term complications. Use of safe and natural foods instead of medications is
      now considered by many scientists. Objectives: This study aimed at determining
      the effect of ginger on lipid and glucose levels of patients with type 2 diabetes
      mellitus. Methods: In a double-blind placebo-controlled trial, 50 patients with
      type 2 diabetes were randomly allocated to 2 groups of intervention (n = 25) and
      placebo (n = 25). Each patient received 2000 mg per day of ginger supplements or
      placebo for 10 weeks. Serum levels of fasting blood sugar (FBS), total
      cholesterol (TC), triacylglycerol (TG), low density lipoprotein cholesterol (LDL
      C), high density lipoprotein cholesterol (HDL-C), and glycosylated hemoglobin
      (HbA1C) were analyzed. Daily dietary intakes and anthropometric parameters were
      also determined. Results: Data from 45 patients were analyzed (23 patients in the
      ginger group and 22 patients in the control group) at the end of the study.
      Ginger consumption significantly reduced serum levels of fasting blood glucose (
      26.30 +/- 35.27 vs. 11.91 +/- 38.58 mg/dl; P = 0.001) and hemoglobin A1C (-0.38
      +/- 0.35 vs. 0.22 +/- 0.29 %; P < 0.0001) compared to the placebo group. Ginger
      consumption also reduced the ratio of LDL-C/HDL-C (2.64 +/- 0.85 vs. 2.35 +/-
      0.8; P = 0.009). However, there was no significant change in serum concentrations
      of triglycerides, total cholesterol, LDL-C, and HDL-C due to the ginger
      supplements. Conclusions: The current results showed that ginger could reduce
      serum levels of fasting blood glucose and hemoglobin A1C in patients with
      diabetes.

PMID- 29344036
TI  - Primordial and Primary Preventions of Thyroid Disease.
AB  - Background: Primordial and primary preventions of thyroid diseases are concerned
      with avoiding the appearance of risk factors, delaying the progression to overt
      disease, and minimizing the impact of illness. Summary: Using related key words,
      446 articles related to primordial and primary, preventions of thyroid diseases
      published between 2001-2015 were evaluated, categorized and analyzed. Prevention
      and elimination of iodine deficiency are major steps that have been successfully
      achieved and maintained in many countries of the world in last 2 decades. Recent
      investigations related to the effect of cigarette smoking, alcohol consumption,
      and autoimmunity in the prevention of thyroid disorders have been reviewed.
      Conclusions: The cornerstone for successful prevention of thyroid disease entails
      timely implementation of its primordial and primary preventions, which must be
      highly prioritized in related health strategies by health authorities.

PMID- 29344038
TI  - An Evaluation of Acupressure on the Sanyinjiao (SP6) and Hugo (LI4) Points on the
      Pain Severity and Length of Labor: A Systematic Review and Meta-analysis Study.
AB  - Background: In this study, the effects of SP6 and LI4 acupressure on the pain
      severity and length of labor are examined. Materials and Methods: This systematic
      review and meta-analysis study was performed on articles published in 2004-2015.
      The articles, published in the English and Farsi languages, related to the
      effects of acupressure on the SP6 and LI4 points on the length and pain severity
      of labor. Data were collected by searching medical databases, including PubMed,
      ISI, MagIran, Google Scholar, Iran Medex, SID, Irandoc, and EMBASE, for relevant
      material. Results: Women who received SP6 acupressure experienced less pain
      immediately after the intervention [-0.56, 95% confidence interval (CI): -0.77, 
      0.36] than women in the touch group and exhibited decrease in the length of labor
      (-0.99, 95% CI: -1.39, -0.39), the active phase (0.95, 95% CI: -1.30, -0.61), and
      the second stage of labor (-0.39, 95% CI: -0.74, -0.03). Women who received LI4
      acupressure experienced less pain immediately after the intervention (-0.94, 95%,
      CI: -1.36, -0.53) than women in the touch group and exhibited shorter active
      phase (-0.91, 95%, CI: -1.18, -0.63) and second stage of labor (-0.55, 95%, CI: 
      0.95, -0.15) lengths. Conclusions: The use of SP6 and LI4 acupressure shows
      promise as a method for managing the length and pain severity of labor, but
      further study is required to establish its effectiveness along with other
      pharmacological and nonpharmacological methods.

PMID- 29344039
TI  - The Effect of Auriculotherapy on the Stress and the Outcomes of Assistant
      Reproductive Technologies in Infertile Women.
AB  - Background: Infertility means failure to achieve pregnancy after one year of
      regular unprotected sexual intercourse. Infertile women may experience severe
      stress and depression. Numerous studies have indicated that auriculotherapy could
      reduce stress. Thus, the aim of the present study was to determine the effect of
      auriculotherapy on the stress and the outcome assisted reproductive technology in
      infertile women. Materials and Methods: The present study was a clinical trial
      that was conducted on 56 infertile women aged 20-45, who were assigned into two
      groups of intervention and control, from November 2014 to November 2015. The
      control group only received the routine treatments, while the intervention group,
      in addition to their routine treatment, received auriculotherapy for 8-10
      sessions during menstrual cycle. Both groups completed Newton's Fertility Problem
      Inventory in three stages. The datasets collected for the study were analyzed
      using independent t-test, repeated-measures analysis of variance, and Chi-square
      test. Results: The mean score of stress in the intervention group decreased
      significantly, compared to the control group prior to the embryo transfer and
      pregnancy test stages. Although insignificant, the rate of pregnancy in the
      intervention group was higher than the control group. There was a significant
      increase in the rate of clinical pregnancy in the intervention group, compared to
      the control. Conclusions: The results indicated that auriculotherapy might be
      effective in reducing stress and improving the outcome of assisted reproductive
      treatment.

PMID- 29344040
TI  - Health Journalism: Health Reporting Status and Challenges.
AB  - Background: Media play crucial role in disseminating health information. Due to
      the importance of accurate health news reports, and the national need to
      professionalism in health journalism, this study aimed to investigate the
      characteristics of health journalists, and health reporting status and the
      challenges involved. Materials and Methods: Using consensus sampling, this
      descriptive cross-sectional study was conducted on all health news reporters in
      Isfahan (34 journalists) in 2015-2016. Data collection was done via a researcher
      made questionnaire. Content validity of the questionnaire was determined by
      qualitative method and based on the opinions of six experts. The test-retest
      reliability coefficient was 98.0. Data analysis was done by Statistical Package
      for the Social Sciences, version 16 and descriptive statistics and content
      analysis were used for analyzing the responses to two open questions. Results:
      Among 34 journalists, 56% were women and 44% men; the majority of journalists
      (65%) had no specialized training on health reporting, 35% of journalists were
      not able to understand the health issues, and the knowledge of medical
      terminology in 59% of them was moderate to low. The most important required skill
      for reporters was the ability to interpret medical research reports (88%), 97%
      were eager to participate in specialized health education. Conclusions: Our study
      showed that health journalists lacked knowledge and specialized training for
      dissemination of health news. This has brought about serious challenges. Thus,
      development and implementation of training courses in close collaboration with
      educational department of the Ministry of Health and news programs professionals
      at Islamic Republic of Iran Broadcasting is highly recommended.

PMID- 29344041
TI  - Impact of Nutrition Education in Improving Dietary Pattern During Pregnancy Based
      on Pender's Health Promotion Model: A Randomized Clinical Trial.
AB  - Background: Different types of nutrients in adequate amounts are required to meet
      the increased demands of the mother and the developing fetus. Therefore, we
      examined the impact of nutrition education on the number of food servings per
      day. Materials and Methods: Pregnant mothers were recruited to a prospective,
      randomized clinical trial from May to September, 2016. At 6-10 weeks of
      gestation, the participants were randomly divided into the intervention (n = 96)
      or the control group (n = 96), and were followed-up until the end of pregnancy.
      Each woman in the experimental group met the study nutritionist at the time of
      enrollment and an individualized nutrition plan was developed. In addition, the
      nutrition education based on Pender's Health Promotion Model (HPM) was designed,
      including three 45-60 min training sessions in 6-10, 18, and 26 weeks of
      pregnancy. The participants' usual food intake using a three-day dietary record
      was assessed at 6-10 weeks and 34-36 weeks of gestation. Results: The mean scores
      of the perceived benefits, self-efficacy, activity-related affect, interpersonal
      influences (husband support), and commitment to action increased while the
      competing demand scores decreased in the interventional group compared with the
      control group. The mean standard deviation (SD) of food portions from grain
      [10.40 (1.96) versus 12.70 (1.93) in the control group], vegetable [3.88 (1.33)
      versus 2.96 (0.91)], fruit [4.02 (0.05) versus 3.95 (0.91)], dairy [2.33 (0.68)
      versus 2.11 (0.45)], and meat [3.17 (0.68) versus 2.96 (0.67)] were improved in
      the experimental group. Conclusions: Pender's HPM for nutrition education is
      effective based on the compliance of pregnant women to the dietary guideline and
      the food guide pyramid.

PMID- 29344042
TI  - Effect of Telephone Follow-up by Nurses on Self-care in Children with Diabetes.
AB  - Background: Diabetes is a serious chronic disease during childhood. Because of
      the chronic nature of the disease, self-care is necessary. Education alone is not
      effective in providing care. Misunderstanding by the patients regarding diabetes
      during the training programs render telephone follow-up after training essential.
      Materials and Methods: This quasi-experimental study with two groups
      (experimental and control) was conducted in two phases in 2014. The study
      population consisted of 70 children of 10-18 years of age with type I diabetes
      (35 patients in the experimental group and 35 in the control group). The
      participants were randomly selected from the patients referring to the Sedigheh
      Tahereh Diabetic Research and Treatment Center in Isfahan, Iran. Data were
      collected using a researcher-made questionnaire on self-care and a glycosylated
      hemoglobin recording form. The experimental group received 12 weeks of telephone
      follow-up training by the center, whereas the control group received no follow
      up. Results: The results showed that, after intervention, the total mean score of
      self-care in all aspects of diabetes care for children was significantly higher
      in the experimental group (p < 0.001). In addition, a statistically significant
      difference was observed between the experimental and control groups in terms of
      mean glycosylated hemoglobin after the intervention (p = 0.030). Conclusions: It
      can be concluded that telephone follow-up by a nurse can improve total self-care
      and glycosylated hemoglobin in patients with type I diabetes.

PMID- 29344043
TI  - Assessment of the Midwifery Students' Clinical Competency Before Internship
      Program in the Field Based on the Objective Structured Clinical Examination.
AB  - Background: One of the important goals of clinical education is to promote the
      level of students' clinical skills. About 50% of the midwifery education is
      focused on clinical education, which has a great importance in shaping the
      professional skills of the students. The aim of this study was to determine the
      ability of students in some practical skills, before internship program in the
      field, using objective structured clinical examination (OSCE). Materials and
      Methods: This research was a descriptive cross-sectional study with a single
      stage, multivariate prospective design. Twenty-seven midwifery students from the
      Isfahan University of Medical Sciences who were in their sixth semester were
      selected by convenience sampling during the second semester of 2015-2016
      educational year. OSCE was executed at skill laboratories in 8 stations during
      one day, and researcher-made checklists were used; their content and face
      validity were approved and their reliability was confirmed by a Cronbach's alpha
      coefficient of 0.97. Data analysis was performed by SPSS19. Results: Results
      showed that the level of students' skills at pelvic exam station was 39.97%, at
      bladder catheterization was 66.92%, at Leopold was 42.7%, at fetal ECG
      interpretation was 50.49%, at physical examination was 21.30%, at fetal
      resuscitation was 48.81%, at breast examination was 56.32%, and at answering the
      questions was 23.49%. Conclusions: Results show that students gained a score of
      less than 50% in most skills. Therefore, they are not efficiently skilled for
      these essential clinical skills. Nonetheless, these procedures need the minimum
      skills that are required from students after graduation and before entering the
      working environment in hospitals and health centers. Therefore, more attention
      should be paid to these skills while planning internship programs before students
      enter the field. Also, more attention is required while teachers teach these
      skills and students are supposed to regard their weaknesses in these skills.

PMID- 29344044
TI  - Ethical Challenges of Embryo Donation in Embryo Donors and Recipients.
AB  - Background: Embryo donation, as one of the novel assisted reproductive
      technologies (ART), has remained a controversial issue. This is due to this
      methods' need for individuals from outside the family circle. Their presence can
      cause many ethical issues and complicate the designing and planning of the embryo
      donation process. The present study was conducted with the aim to assess the
      ethical challenges of embryo donation from the view point of embryo donors and
      recipients. Material and Methods: This descriptive, cross-sectional study was
      conducted on 192 couples (96 embryo donators and 96 embryo recipients) referring
      to Isfahan Fertility and Infertility Center and Royan Institute, Iran. The
      subjects were selected through convenience sampling. The data collection tool was
      the researcher-made Ethical Challenges Questionnaire. Data were analyzed in SPSS
      software. Results: Embryo donors and recipients expresses the most important
      ethical challenges of embryo donation in the principle of justice (70.20%) and
      respect for autonomy (42.57%), respectively. Conclusions: The four ethical
      principles are important in the view of embryo donors and recipients; however,
      they highlighted the importance of the principle of respect for autonomy
      considering the existing barriers in the services of infertility centers.
      Legislators and relevant authorities must take measures toward the development of
      guidelines for this treatment method in the framework of ethics principles and
      incorporate all four principles independently.

PMID- 29344045
TI  - Predicting Nurses' Psychological Safety Based on the Forgiveness Skill.
AB  - Background: Forgiveness, as an intentional denial of your right of anger and
      aversion from a harmful deed, is related to many psychological processes of human
      which results in more psychological safety for people. The present study aimed to
      predict the psychological safety of nurses through different dimensions of
      forgiveness skill. Materials and Methods: This correlational study was conducted
      on 170 nurses working in Kerman hospitals during 2016-2017 who were selected
      based on convenience random sampling. Edmondson psychological safety and Thompson
      Heartland forgiveness scale were used for data collection. Data were analyzed
      through Pearson correlation coefficient and multiple regression model. Results:
      TThe results indicated that psychological safety has a significant relationship
      with self-forgiveness (p = 0.0001) and other-forgiveness (p = 0.04). Further,
      only self-forgiveness could significantly predict 0.07 of psychological safety
      variance (p = 0.003). Conclusions: Self-forgiveness skill can improve the nurses'
      psychological safety and reduce the harms caused by job pressures by reinforcing
      positive psychological factors. It is recommended to teach forgiveness skill
      through holding in-service classes to staff and study the relationship between
      psychological safety with other social life skills among nurses.

PMID- 29344046
TI  - Relationship between Spiritual Intelligence with Happiness and Fear of Childbirth
      in Iranian Pregnant Women.
AB  - Background: Spiritual intelligence is a person's ability to feel a connection to
      a higher power and a sacred entity. With regard to its relation with happiness,
      it can have an important effect on the mental health of pregnant women.
      Therefore, this study aimed to investigate the relationship between spiritual
      intelligence and happiness and fear of childbirth in pregnant women. Materials
      and Methods: This cross-sectional study was conducted on 245 low-risk pregnant
      women from June till September 2015. Using random cluster sampling method, the
      subjects were selected among the women who referred to health care centers in
      Shahroud (Northeast of Iran). After obtaining informed consent, the researchers
      evaluated the spiritual intelligence, happiness, and fear of childbirth. Data
      were analyzed using STATA12 and Chi-square test, t-test, analysis of variance,
      and Strucrural Equation Model. Results: In this study, the spiritual intelligence
      mean (SD) score was 64.43(16.51). Comparison between mothers with and without
      fear of childbirth showed there was a significant difference between the
      spiritual intelligence score and happiness mean scores in these two groups. There
      is a negative correlation between spiritual intelligence and happiness with fear
      of childbirth (-0.73 and -0.69, respectively). Conclusions: Increased level of
      spiritual intelligence in pregnant women can lead to an increase in their
      happiness and reduce their fear of childbirth. The fear of childbirth can be
      prevented via trainings to pregnant women about the components of spiritual
      intelligence; moreover, training the techniques to achieve more happiness can
      help mothers to reduce their fear of childbirth and hence promote natural
      childbirth.

PMID- 29344047
TI  - A Comparative Study of Shift Work Effects and Injuries among Nurses Working in
      Rotating Night and Day Shifts in a Tertiary Care Hospital of North India.
AB  - Background: Shift work can have an impact on the physical and psychological well
      being of the healthcare worker, affecting patients as well as their own safety at
      the workplace. This study was conducted to compare the health outcomes and
      injuries, along with associated risk factors between the nurses working in
      rotating night shift (RNS) as compared to day shift (DS) only. Materials and
      Methods: It was a cross-sectional study conducted from June to November 2016 in a
      tertiary care hospital of Delhi. It involved 275 nurses working in RNS and 275
      nurses from DS of various departments, selected through simple random sampling.
      Standard Shift Work Index Questionnaire (SSI) was used as the study instrument,
      with selected variables (according to objectives of the study). Data were
      analyzed using descriptive statistics, Chi-square, t-test, and multivariate
      regression. Results: Female nurses had more sleep disturbance, fatigue, and poor
      psychological health. Working on a contractual basis, RNS, and living outside the
      hospital campus were associated with higher odds of having needle stick injury
      (NSI). The nurses working in RNSs were found to have significantly lower mean
      scores in job satisfaction (p = 0.04), sleep (p < 0.001), and psychological well
      being (p = 0.047) as compared to DS workers. Conclusions: Health outcomes among
      nurses working in RNSs call for the interventions, focused on various factors
      which can be modified to provide supportive and safer working environment.

PMID- 29344048
TI  - The Impact of Normal Saline on the Incidence of Exposure Keratopathy in Patients
      Hospitalized in Intensive Care Units.
AB  - Background: Patients in the intensive care unit (ICU) have impaired ocular
      protective mechanisms that lead to an increased risk of ocular surface diseases
      including exposure keratopathy (EK). This study was designed to evaluate the
      effect of normal saline (NS) on the incidence and severity of EK in critically
      ill patients. Materials and Methods: This single-blind randomized controlled
      trial was conducted on 50 patients admitted to ICUs. The participants were
      selected through purposive sampling. One eye of each patient, randomly was
      allocated to intervention group (standard care with NS) and the other eye to
      control group (standard care). In each patient, one eye (control group) randomly
      received standard care and the other eye (intervention group) received NS every 6
      h in addition to standard care. The presence and severity of keratopathy was
      assessed daily until day 7 of hospitalization using fluorescein and an
      ophthalmoscope with cobalt blue filter. Chi-square test was used for statistical
      analysis in SPSS software. Results: Before the study ( first day) there were no
      statistically significant differences in the incidence and severity of EK between
      groups. Although, the incidence and severity of EK after the study (7th day) was
      higher in the intervention group compared to the control group, their differences
      were not statistically significant. Although, the incidence and severity of EK,
      from the 1st day until the 7th, increased within both groups, this increase was
      statistically significant only in the intervention (NS) group. Conclusions: The
      use of NS as eye care in patients hospitalized in ICUs can increase the incidence
      and severity of EK and is not recommended.

PMID- 29344049
TI  - A Structural Equation Model of Self-care Activities in Diabetic Elderly Patients.
AB  - Background: Self-care is a valuable strategy to improve health and reduce events
      of hospitalization and the duration of hospital stay in elderly diabetic
      patients. This study aimed to examine the model of self-care behaviors in elderly
      diabetic patients. Materials and Methods: A survey was conducted among 209
      diabetic elderly patients who were admitted in three hospitals affiliated with
      the Isfahan University of Medical Sciences, Iran. Convenience sampling method was
      used to recruit the participants. Depression, anxiety, stress, and perceived
      social support were considered as predicting exogenous variables and elderly
      patients' self-care activities were treated as endogenous variables. The data
      were collected by a four-part questionnaire consisting of demographic and health
      related characteristics; 21-item depression anxiety stress scale,
      multidimensional scale of perceived social support, and Diabetes Self-care
      Activities scale. Structural equation modelling by Statistical Package for the
      Social Sciences (SPSS) version 16 and Analysis of Moment Structures-7 (AMOS)
      software was applied for data analysis. Results: Mean (standard deviation) of
      depression, anxiety, stress, perceived social support, and self-care activities
      of participants were 14.29 (4.3), 13.62 (3.74), 16.83 (4.23), 57.33 (14.19), and
      44.56 (13.77), respectively. The results showed that the overall model fitted the
      data (chi2/df = 3.8, goodness-of-fit index (GFI) = 0.52, incremental fit index
      (IFI) = 0.48, and root mean square error of approximation (RMSEA) = 0.14). Three
      out of four variables (i.e., perceived social support, anxiety, and depression)
      significantly predicted adherence to self-care behaviors among diabetic elderly
      patients (p < 0.05). Conclusions: The perceived social support, anxiety, and
      depression were identified as key constructs which need to be taken into account
      and well managed by health care professionals to enhance adherence to self-care
      activities in diabetic elderly patients.

PMID- 29344050
TI  - The Lived Experiences of Becoming First-line Nurse Managers: A Phenomenological
      Study.
AB  - Background: Designated roles of first-line nurse managers (FLNMs) are very
      complex, this study aimed to develop a deeper understanding of their meaningful
      lived experiences. Materials and Methods: This study employed a phenomenological
      study using semi-structured interviews with FLNMs (n = 7) at the General Hospital
      of Belitung, Indonesia. The data analysis was thematic. Results: Four major
      themes were identified from the analysis of textual data: Feeling extraordinary,
      the inability to do, desire to leave the unit, and influenced by work motivation.
      The findings of this study revealed the positive and negative experiences of
      becoming FLNMs. The positive experiences were related to the feeling challenged
      and extraordinary to deal with many roles in management and leadership. The
      negative experiences included personal conflict related to the desire to leave
      the unit, and feeling unable to manage. However, the works of FLNMs were
      influenced by internal and external motivation. Conclusions: This study better
      informs nurse executives to develop competence and performance of FLNMs, and keep
      their motivation by revising performance appraisal system.

PMID- 29344051
TI  - Experiences of Fathers with Inpatient Premature Neonates: Phenomenological
      Interpretative Analysis.
AB  - Background: Birth and hospitalization of premature neonates create enormous
      challenges for the family with serious impacts on parents' mental and emotional
      health. The present study was designed to explore the experiences of fathers with
      premature neonates hospitalized in a neonatal intensive care unit (NICU).
      Materials and Methods: In this interpretative phenomenological study, data were
      collected using in-depth interviews guided with a semi-structured questionnaire
      and analyzed by interpretative phenomenological analysis. Totally seven
      interviews were conducted with six participants. Results: The mean age of the
      fathers was 32 (23-42) years, and all of the fathers lived with their wives.
      Experiences of the fathers were categorized into 13 subordinate and three
      superordinate themes: "abandonment and helplessness" (lack of financial support,
      lack of informational support, and indignation and distrust toward the hospital
      staffs); "anxiety and confusion" (family disruption, shock due to the premature
      birth of the neonate, uncertainty, the loss of wishes, feeling of guilt and
      blame, and occupational disruption); and "development and self-actualization"
      (emotional development, spiritual development, independence and self-efficacy,
      and responsibility). Conclusions: The present study showed that the fathers with
      premature neonates hospitalized in NICU encounter both positive (development and
      self-actualization) and negative experiences (lack of financial and informational
      supports, distrusting toward the hospital staffs, family disruption, and
      occupational disruption). Planning to manage adverse experiences can help fathers
      to cope with this situation.

PMID- 29344053
TI  - An overview of exposure to ethanol-containing substances and ethanol intoxication
      in children based on three illustrated cases.
AB  - Alcohol addiction and intoxication are major health problems worldwide. Acute
      alcohol intoxication is well reported in adults and adolescents but less
      frequently reported in children of younger ages. We report three anonymized cases
      of pediatric ethanol exposure and illustrate the different mechanisms of
      intoxication. In all cases, a focused history is the key to prompt diagnosis and
      timely management. Physicians should be aware of this potential poison in
      children presented with acute confusional or encephalopathic state. In contrast,
      neonates with ethanol intoxication may present with nonspecific gastrointestinal
      symptomatology. Urgent exclusion of sepsis, electrolyte imbalance, drug
      intoxication, and surgical abdominal condition is critical. Using these
      illustrated cases, we performed a narrative literature review on issues of
      exposure to ethanol-containing substances and ethanol intoxication in children.
      In conclusion, a high level of suspicion and interrogation on ethanol or
      substance use are essential particularly in the lactating mother for an accurate
      and timely diagnosis of ethanol intoxication to be made.

PMID- 29344052
TI  - Manidipine: an antihypertensive drug with positive effects on metabolic
      parameters and adrenergic tone in patients with diabetes.
AB  - Antihypertensive treatment of patients with diabetes should include those drugs
      with a positive effect on metabolic parameters. Most patients with diabetes
      require at least two antihypertensive agents. Combining a dihydropyridine calcium
      channel blocker with a renin-angiotensin-aldosterone system inhibitor is a
      rational approach. However, not all dihydropyridines are equal with respect to
      their effects on metabolic parameters. Thus, manidipine exerts a positive effect
      on insulin resistance. However, this effect has not been observed with
      amlodipine. On the other hand, the excessive activation of sympathetic nervous
      system has been related with an increase of insulin resistance, pulse pressure,
      and ankle edema rates. Compared with amlodipine, manidipine activates sympathetic
      nervous system to a lesser extent. As a result, treatment with manidipine
      represents a good option in hypertensive patients with diabetes.

PMID- 29344054
TI  - The carnitine status does not affect the contractile and metabolic phenotype of
      skeletal muscle in pigs.
AB  - Background: Recently, supplementation of L-carnitine to obese rats was found to
      improve the carnitine status and to counteract an obesity-induced muscle fiber
      transition from type I to type II. However, it has not been resolved if the
      change of muscle fiber distribution induced in obese rats and the restoration of
      the "normal" muscle fiber distribution, which is found in lean rats, in obese
      rats by supplemental L-carnitine is causally linked with the carnitine status. In
      the present study we hypothesized that fiber type distribution in skeletal muscle
      is dependent on carnitine status. Methods: To test this, an experiment with 48
      piglets which were randomly allocated to four groups (n = 12) was performed. All
      piglets were given orally either 60 mg sodium bicarbonate/kg body weight (group
      CON), 20 mg L-carnitine and 60 mg sodium bicarbonate/kg body weight (group CARN),
      30 mg pivalate (dissolved in sodium bicarbonate)/kg body weight (group PIV) or 20
      mg L-carnitine and 30 mg pivalate/kg body weight (group CARN + PIV) each day for
      a period of 4 weeks. Results: Concentrations of total carnitine in plasma, liver
      and longissimus dorsi and biceps femoris muscles were 2.0-2.7 fold higher in
      group CARN than in group CON, whereas these concentrations were 1.9-2.5-fold
      lower in group PIV than in group CON. The concentrations of total carnitine in
      these tissues did not statistically differ between group CARN + PIV and group
      CON. Fiber type distribution of longissimus dorsi and biceps femoris muscles,
      mRNA and protein levels of molecular regulators of fiber distribution in
      longissimus dorsi and biceps femoris muscles and mRNA levels of genes reflecting
      the metabolic phenotype of longissimus dorsi and biceps femoris muscles did not
      differ between groups. Conclusion: Changes in the systemic carnitine status and
      the muscle carnitine concentration induced by either supplementing L-carnitine or
      administering pivalate have no impact on the contractile and metabolic phenotype
      of skeletal muscles in pigs.

PMID- 29344055
TI  - Non-organic Vision Loss in the Afghanistan and Iraq Conflicts.
AB  - Non-organic visual loss (NOVL), defined as a decrease in visual acuity or field
      without an identifiable organic cause, can be challenging to diagnose, especially
      in patients whose NOVL is superimposed on some component of true organic
      pathology. Exposure to combat puts soldiers at risk of emotional distress and
      physical trauma, which can contribute to the development of NOVL with conversion
      disorder or malingering. This case series describes six patients with NOVL who
      sustained ocular or non-ocular injuries while serving in combat operations in
      Iraq and Afghanistan, and highlights diagnostic pearls and components of inter
      disciplinary management in the unique military context.

PMID- 29344056
TI  - Effects of Contrast Sensitivity on Colour Vision Testing.
AB  - This study analyses how contrast sensitivity loss affects colour vision (CV)
      testing. Eleven participants were scored while cycling through randomly arranged
      pictures of CV tests with varying levels of contrast changes applied. Hardy-Rand
      Rittler (HRR) scores declined significantly at each successive decrease in
      contrast level after the highest setting (p < 0.004). HRR scores were also lower
      than those for Ishihara and Farnsworth D-15 tests at two contrast settings (p <
      0.01). Contrast changes had the greatest impact on HRR scores, indicating that
      this test may not be an accurate reflection of CV in patients with contrast
      sensitivity loss.

PMID- 29344057
TI  - Causes and Prognosis of Unilateral and Bilateral Optic Disc Swelling.
AB  - The authors reviewed 93 consecutive cases with optic disc swelling (ODS) to
      compare clinical manifestations and prognosis among the causes. Among unilateral
      ODS patients >=50 years old and without pain, anterior ischaemic optic neuropathy
      accounted for 87.5%. Furthermore, papilloedema (PE) presented unilateral ODS with
      an atrophic or hypoplastic disc in the opposite eye. Despite no differences for
      age and initial visual acuity between PE and pseudopapilloedema, the two main
      causes of bilateral ODS, some PE patients showed poor visual prognosis.
      Understanding differences in frequencies and clinical features of ODS related to
      cause and age group can help to accurately determine cause and predict outcome.

PMID- 29344058
TI  - An Estimation of the Risk of Pseudotumor Cerebri among Users of the
      Levonorgestrel Intrauterine Device.
AB  - Because of a previous association of pseudotumor cerebri (PTC) with
      levonorgestrel, we wished to evaluate the use of levonorgestrel-eluting
      intrauterine devices ("levonorgestrel intrauterine systems", LNG-IUS) in our
      University of Utah and Rigshospitalet PTC patients. In our retrospective series,
      PTC prevalence was approximately 0.18% and 0.15% in the LNG-IUS population versus
      0.02% and 0.04% in the non-LNG-IUS population (Utah and Rigshospitalet,
      respectively), with no significant differences in PTC signs and symptoms among
      the two groups. Our investigation suggests that women with an LNG-IUS may have
      increased risk of developing PTC but does not suggest an LNG-IUS can cause PTC.

PMID- 29344059
TI  - Retinitis Pigmentosa Sine Pigmento Mimicking a Chiasm Disease.
AB  - A 75-year-old woman presented to her ophthalmologist complaining of visual loss
      for several years. The ophthalmic examination was remarkable for a bitemporal
      visual field defect. Magnetic resonance imaging (MRI) scan of the brain was
      normal without evidence of chiasm compression. Neuro-ophthalmic examination was
      consistent with a retinal rather than a chiasmal disease. Retinal multimodal
      imaging helped in the correct diagnosis of retinitis pigmentosa, later confirmed
      by genetic testing.

PMID- 29344060
TI  - Neuro-Ophthalmic Presentation of Neuro-Sweet Disease.
AB  - Acute febrile neutrophilic dermatosis (Sweet syndrome) is a systemic inflammatory
      condition usually associated with autoimmune or neoplastic processes and
      characterised by inflammatory dermatologic lesions such as erythematous plaques
      and papules associated with fever and leukocytosis. Neurological and
      ophthalmological involvement is rare. The authors describe an unusual case of
      Sweet syndrome associated with microscopic polyangiitis presenting with
      papilloedema, anterior uveitis, and skin rash. Years later, he developed acute
      posterior multifocal placoid pigment epitheliopathy. Treatment with
      immunosuppressive medications led to a relapsing remitting course with maximum
      benefit from use of steroids. The authors describe the difficulties in diagnosis
      and treatment of this rare case.

PMID- 29344061
TI  - Subacute Acrylamide Intoxication with Severe Visual Disturbance: A Case Report.
AB  - A 35-year-old man was admitted due to somnolence and progressive sensory-motor
      polyneuropathy, followed by severe visual impairment in both eyes after direct
      skin exposure to an acrylamide monomer solution. The results of an
      ophthalmological examination including central critical flicker fusion frequency
      and the decreased amplitude of action potentials observed in the visual evoked
      potential studies suggested that acrylamide intoxication resulted in neuronal
      degeneration in the optic pathways. Additional attention should be directed to
      the potential effect of acrylamide on the human visual system.

PMID- 29344062
TI  - Cystic Optic Chiasm Lesion: Atypical Magnetic Resonance Imaging Findings.
AB  - Intrinsic cystic lesions in the optic chiasm are an uncommon cause of bitemporal
      hemianopia compared with compressive lesions extrinsic to the chiasm. A 40-year
      old man presented with difficulty driving. Clinical assessment revealed a
      bitemporal hemianopia. Magnetic resonance imaging showed an unusual cystic
      appearance of the chiasm. The appearance was felt to be most likely secondary to
      previous infective or inflammatory disease, but biopsy was not undertaken given
      the very significant risk of further visual loss.

PMID- 29344063
TI  - Axonal Injury in the Lateral Geniculate Body: Radiological Diagnosis.
AB  - Damage to the lateral geniculate body by diffuse axonal injury in brain trauma is
      uncommon. The authors present the clinical case and in vivo fibre tractography
      using diffusion tensor magnetic resonance imaging of this lesion in a patient
      presenting with homonymous sectoranopia after a traumatic head injury.

PMID- 29344064
TI  - Occult Acute Macular Neuroretinopathy.
AB  - A 19-year-old Caucasian woman developed an upper respiratory infection, took a
      cold formulation containing 5 mg of phenylephrine, and developed a very rare and
      unusual form of acute macular neuroretinopathy (AMN) that could not be detected
      on fundoscopic examination, visual fields, nor electrophysiological testing.
      Spectral-domain optical coherence tomography (SD-OCT) revealed a lesion limited
      to the fovea. This case illustrates the value of SD-OCT, in light of otherwise
      normal testing, in a variant of AMN the authors call "occult AMN".

PMID- 29344065
TI  - Optociliary Shunt Vessels: Role in Diagnosis and Treatment of Atypical
      Pseudotumor Cerebri.
AB  - A 46-year-old man presented with severe visual loss and optic atrophy associated
      with optociliary shunt vessels. The diagnostic work-up revealed intracranial
      hypertension and cerebral venous sinus stenosis, with no evidence of previous
      thrombosis. In view of the severe visual dysfunction, both eyes were submitted to
      optic nerve sheath fenestration. After surgery, a regression of collateral
      vessels was observed in both eyes.

PMID- 29344066
TI  - Diagnostic Challenge: Sequential Unilateral Cranial Neuropathies Due to
      Perineural Spread of Carcinoma.
AB  - An 86-year old man developed sequential dysfunction of trigeminal (V1), facial,
      abducens, trigeminal (v2), oculomotor, and hypoglossal cranial nerves on the
      right over 20 months. Magnetic resonance imaging (MRI) showed a lesion in the
      right cavernous sinus. Although there was clinical suspicion that this was
      related to perineural spread of an extracranial tumour, a primary lesion was not
      discovered. Stereotactic biopsies of the intracranial lesion were non-diagnostic,
      and the patient succumbed to his tumour following a period of rapid growth.
      Postmortem examination showed the intracranial lesion to be a carcinoma with
      squamous features. This case highlights the challenges of diagnosis of
      intracranial perineural spread and the potential for transformation from indolent
      to aggressive tumour behaviour.

PMID- 29344067
TI  - Corrigendum.
AB  - [This corrects the article DOI: 10.1080/01658107.2016.1263343.].

PMID- 29344069
TI  - Pituitary Ring Sign Plus Sphenoid Sinus Mucosal Thickening: Neuroimaging Signs of
      Pituitary Apoplexy.
AB  - Two magnetic resonance imaging (MRI) signs of pituitary apoplexy are the
      "pituitary ring sign" and "sphenoid sinus mucosal thickening". The occurrence of
      both these MRI signs together in patients with ischaemic pituitary apoplexy was
      investigated. A literature review searching the terms "pituitary ring sign" and
      "sphenoid sinus mucosal thickening" in the context of pituitary apoplexy from
      1990 until present was performed. To be included in the study, each case had to
      have ischaemic pituitary apoplexy defined as acute expansion of a pituitary
      adenoma or, less commonly, in a non-adenomatous gland, from infarction without
      haemorrhage or very little haemorrhage and a T1-weighted MRI of the brain with
      contrast that displayed both "sphenoid sinus mucosal thickening" and a "pituitary
      ring sign" either on an actual study (the author's cases) or in a figure in an
      article from the literature that could be reviewed and clearly illustrate these
      two signs. Twelve cases of ischaemic pituitary apoplexy were found, all with MRI
      images that showed both of these signs. Ten cases from the literature (3 of which
      were published by this author) plus an additional 2 recently evaluated in our
      hospital, totalled the 12 cases. Thus, 5 of the total 12 cases were evaluated by
      this author. Of these 12 patients, both headache and visual loss were present in
      5 patients, headache alone was indicated in 5 patients (10 of the 12 presented
      with headache), and no initial symptoms identified in 2 patients (incidentally
      found non-functioning pituitary adenomas on MRI). These findings indicate that
      each sign ("pituitary ring sign" and "sphenoid sinus mucosal thickening") may
      exist alone with or without pituitary apoplexy, yet both signs together in the
      appropriate clinical context is a strong predictor of pituitary apoplexy.

PMID- 29344068
TI  - Clinical versus Evidence-based Rehabilitation Options for Post-stroke Visual
      Impairment.
AB  - The aim of this study was to identify which treatments for post-stroke visual
      impairment have a supportive evidence base, and which are being used in practice
      without supportive evidence. A systematic review of the literature reporting on
      the available treatment options was compared against the visual treatments used
      in the Vision In Stroke (VIS) study. Treatments were identified for visual field,
      visual neglect, visual perception and ocular motility disorders. Visual scanning
      therapies for hemianopia and neglect have an established evidence base. However,
      a number, such as typoscopes and advice options, have limited detail of their
      effectiveness and require further research.

PMID- 29344070
TI  - Diffuse Colour Discrimination as Marker of Afferent Visual System Dysfunction in
      Amyotrophic Lateral Sclerosis.
AB  - Abnormalities of the inner and intermediate retinal structures in patients with
      amyotrophic lateral sclerosis (ALS) have been described using optical coherence
      tomography and histopathology. Colour vision is a potential marker of these
      structural changes. The purpose of this study is to test the hypothesis that
      colour vision impairment is associated with ALS. Monocular (right eye) colour
      vision was assessed in subjects with definite or probable ALS (n = 25, aged 50-80
      years) and control (n = 21, aged 46-89 years) subjects with corrected near visual
      acuity of at least 20/40 using the L'Anthony D15 color test (desaturated), scored
      by c-index, a measure of diffuse colour discrimination. Of ALS subjects, 16/25
      (64%) had impaired colour vision (c-index >1.8). Comparing with our normal
      subjects and accounting for age, 72% (n = 18) of ALS subjects had colour vision
      below the 50th percentile, 52% (n = 13) had colour vision below the 25th
      percentile, 24% (n = 6) had colour vision below the 10th percentile, and 8% (n =
      2) had colour vision below the 2nd percentile. In multivariate models of ln(c
      index) and age, the intercept was higher and the slope was flatter in ALS
      subjects, suggesting that colour vision deficits are more prominent in younger
      ALS patients. Diffuse colour discrimination deficits are detected in ALS subjects
      at younger ages than in control subjects. Further study is needed to confirm
      these findings and to determine if the ALS colour discrimination abnormalities
      correlate with structural markers of retinal involvement and ALS disease
      severity.

PMID- 29344071
TI  - Acetazolamide: A New Treatment for Visual Vertigo.
AB  - Visual vertigo is a disorder characterised by symptoms of dizziness, vertigo,
      unsteadiness, disorientation, and general discomfort induced by visual triggers.
      It is currently treated with vestibular rehabilitation therapy, with no effective
      pharmacotherapy available for treatment-resistant cases. The objective of this
      study was to evaluate the efficacy of oral acetazolamide in improving symptoms of
      visual vertigo. A comparative case series of adult patients clinically diagnosed
      with visual vertigo was conducted from January 1992 to May 2015. Patients without
      a full neurologic or otorhinolaryngologic work-up, negative magnetic resonance
      imaging (MRI), and an organic cause for their symptoms were excluded. The
      identified patients were then contacted by phone to complete a voluntary symptom
      survey. Main outcome was the subjective reported percentage in symptom
      improvement. Secondary outcomes were subjective improvement by symptom triggers.
      The participants were retrospectively divided into three groups based on their
      treatment with acetazolamide: currently on acetazolamide, terminated
      acetazolamide, or never initiated acetazolamide. Fifty-seven patients met the
      inclusion criteria and were willing to complete the phone survey (19 currently on
      acetazolamide, 27 terminated acetazolamide, and 11 never initiated therapy).
      Overall symptomatic improvement was reported by 18 (94.7%) patients currently on
      acetazolamide, 18 (66.7 %) who terminated acetazolamide, and 5 (45.5%) who never
      initiated therapy, varying significantly by group (p = 0.0061). Greatest
      improvement was reported in symptoms triggered by being a passenger in a car.
      These results show that acetazolamide has a positive association with improvement
      of symptoms of visual vertigo.

PMID- 29344072
TI  - Bilateral Compressive Optic Neuropathy from Renal Osteodystrophy Caused by
      Branchio-oto-renal Syndrome Stabilised After Parathyroidectomy.
AB  - Renal osteodystrophy can cause calvarial hypertrophy and narrowing of the neural
      canals and foramina. Compressive optic neuropathy is extremely rare in renal
      osteodystrophy and was reported once only. The authors report bilateral,
      simultaneous compressive optic neuropathy secondary to renal osteodystrophy with
      features of uremic leontiasis ossea in chronic renal failure caused by branchio
      oto-renal syndrome. Because of the extensive calvarial hypertrophy and the
      surgical difficulties envisaged with optic canal decompression, conservative
      approach was pursued. The patient's visual acuity and fields improved after
      partial parathyroidectomy. Visual improvement may be explained by the arrest of
      renal osteodystrophy and reduced optic nerve compression after parathyroidectomy.

PMID- 29344073
TI  - Bilateral Non-arteritic Anterior Ischaemic Optic Neuropathy as the Presentation
      of Systemic Amyloidosis.
AB  - A 75-year-old hypertensive female with stable idiopathic intermediate uveitis
      presented with bilateral sequential optic neuropathy with optic disc swelling.
      The optic neuropathy in the first affected eye (right) was thought to be due to
      non-arteritic anterior ischaemic optic neuropathy (NAION). Asymptomatic left
      optic disc swelling was found at routine review 2 months later, and a diagnosis
      of giant cell arteritis (GCA) was sought. Temporal artery duplex ultrasound
      showed the "halo sign," but a subsequent temporal artery biopsy showed light
      chain (AL) amyloidosis with no signs of giant cell arteritis. In this case,
      bilateral sequential ischaemic optic neuropathy mimicking non-arteritic anterior
      ischaemic optic neuropathy was the presenting sign of systemic amyloidosis
      involving the temporal arteries.

PMID- 29344074
TI  - Proceedings of the 38th Annual Upper Midwest Neuro-Ophthalmology Group Meeting,
      July 28, 2017, Chicago, Illinois, USA.

PMID- 29344075
TI  - Reply to: "Bilateral Non-arteritic Anterior Ischaemic Optic Neuropathy as the
      Presentation of Systemic Amyloidosis".

PMID- 29344076
TI  - Response to Dr. Pellegrini Regarding Comments on "Bilateral Non-arteritic
      Anterior Ischaemic Optic Neuropathy as the Presentation of Systemic Amyloidosis".

PMID- 29344078
TI  - Application of the ICF based Norwegian function assessment scale to employees in
      Germany.
AB  - Background: At the interface of the occupational setting and rehabilitation,
      normative values for functional ability are desirable and worthwhile. The
      Norwegian Function Assessment Scale (NFAS) is a 39 item self-report instrument
      based on the International Classification of Functioning, Disability and Health
      (ICF). As the questionnaire was not used in a working population, we aimed to
      obtain functional levels of employees in Germany as measured through the NFAS.
      Methods: The NFAS was included in the Study on Mental Health at Work (S-MGA)
      2011/12, a representative German survey of employees aged 31 to 60 years. For
      descriptive analyses, 95% confidence intervals were applied through bootstrap
      estimation to the skewed data of the NFAS (range from 1 = 'no difficulty' to 5 =
      'could not do it'). The data were analysed by age decades, professional
      qualification, and by disabilities, congenital diseases and accidents, stratified
      by sex. Linear regression analyses were conducted to estimate adjusted effects of
      age, professional qualification, and health limitations. Results: The NFAS total
      score was 1.17 (95% CI = 1.15-1.17). Thirty-five percent of the employees' (1378
      out of 3937 participants) reported the best possible functional ability (NFAS
      total score of 1.00). Managing and walking/standing were the NFAS' most affected
      domains with a score of 1.26 (95% CI = 1.23-1.27), respectively. The regression
      analysis confirmed more functional difficulties for elder employees, females,
      employees with low professional qualification, and for employees suffering from
      disability and accidents. Conclusions: The study presents normative values of
      functional ability for the workforce. The results are useful for score
      interpretation in rehabilitation and return-to-work processes.

PMID- 29344079
TI  - Factors associated with breastfeeding intent among mothers of newborn babies in
      Da Nang, Viet Nam.
AB  - Background: Breastfeeding is recognized as the single most cost-effective
      intervention to reduce child morbidity and mortality. However, few studies have
      explored perceived barriers to breastfeeding and factors associated with
      breastfeeding intent among mothers of newborn babies in Viet Nam. We conducted a
      study to assess breastfeeding initiation rates, intent to breastfeed exclusively
      for 6 months or more and perceived barriers to breastfeed among mothers of
      newborn babies in Da Nang, Viet Nam. Methods: We conducted a cross-sectional
      questionnaire survey of mothers in the postnatal wards of Da Nang Hospital for
      Women and Children in central Viet Nam from 10 February 2017 to 24 February 2017,
      following implementation of the World Health Organization (WHO) Essential Newborn
      Care (ENC) package. Results: Of 286 mothers surveyed, 259 (90.6%) initiated
      breastfeeding; 203/258 (78.7%) within 1 hour (h) of birth. Most (207, 72.4%)
      mothers indicated intent to breastfeed exclusively for 6 months or more, but this
      was lower among mothers of preterm babies (82.2% versus 20.0%, p < 0.001) and
      those without post-secondary school education (74.8% versus 55.6%, p = 0.02).
      Amongst mothers struggling to establish breastfeeding, 18/27 (66.7%) had a
      Cesarean section. Planned non-exclusive breastfeeding was mostly (39, 60.9%)
      motivated by mothers' concern that their milk supply would be insufficient for
      their baby's growth requirements. Most mothers had good knowledge about the
      benefits of breastfeeding and indicated strong decision autonomy. Conclusions: We
      documented high rates of early breastfeeding establishment and intent to
      breastfeed exclusively for 6 months or more. This probably reflects high levels
      of maternal education and successful implementation of the WHO ENC package.
      Mothers of premature babies may benefit from additional support.

PMID- 29344081
TI  - HPV infection and P16 expression in oral and oropharyngeal cancer in Kazakhstan.
AB  - Background: Human papillomavirus (HPV) is an important etiologic factor in
      different cancers of anogenital region and also in a fraction of head and neck
      cancers (HNC) particularly oropharyngeal tumors. The HPV16 genotype associated
      with the majority of HPV-related head and neck carcinomas. Th incidence of
      oropharyngeal cancer is increasing in many countries, and the rate of HPV
      positive tumors is about 70% in Europe and North America. Little known about the
      prevalence of HPV in HNC in Central Asia. Methods: It's a prospective analysis of
      patients with verified oral or oropharyngeal cancer. Sociodemographic and
      clinical data obtained on admission to treatment. The diagnosis of HPV positivity
      assessed by both the P16 expression on immunohistochemistry(IHC) and polymerase
      chain reaction (PCR)with HPV DNA detection and HR HPV type determination.
      Results: Seventy six patients with oral and oropharyngeal cancer tested for HPV.
      Forteen cases were positive for HPV by PCR and 15 cases by P16 IHC. Of the 35
      oropharyngeal tumors, nine were HPV DNA and p16 IHC positive, giving the rate of
      25.7%. Of the 41 oral tumors, five were HPV DNA and six p16 IHC positive, giving
      the rate of 12.2%. Conclusion: It is the first study mapping prevalence of HPV
      positivity in oral and oropharyngeal cancer in the Central Asian region. The rate
      of HPV positivity was higher in oropharyngeal than in oral cancer, the nonsmokers
      were significantly more frequent in the HPV positive group and HPV 16 was the
      most frequent type. However, the HPV positivity rates are lower than referred in
      the western world.

PMID- 29344080
TI  - Effects of Huang Bai (Phellodendri Cortex) on bone growth and pubertal
      development in adolescent female rats.
AB  - Background: To evaluate the effects of Huang Bai (Phellodendron amurense) on
      growth and maturation in adolescent female rats. Methods: Female Sprague-Dawley
      rats (28 days old; n = 72) were divided into six daily treatment groups: control
      (distilled water), Huang Bai (100 and 300 mg/kg), recombinant human GH (rhGH; 20
      MUg/kg), estradiol (1 MUg/kg), and triptorelin (100 MUg). Body weight, food
      intake, and vaginal opening were measured daily from postnatal day (PND) 28 to
      PND 43. Tetracycline (20 mg/kg) was injected on PND 41. After sacrifice on PND
      43, the ovaries and uterus were weighed, and the tibias were fixed in 4%
      paraformaldehyde. Decalcified and dehydrated tibias were sectioned at a thickness
      of 40 MUm, and sectioned tissues were examined with a fluorescence microscope.
      Insulin-like growth factor (IGF)-1 and bone morphogenetic protein (BMP)-2 were
      detected using immunohistochemistry. Results: Relative to controls, body weight
      was higher in the triptorelin group. Bone growth rate increased in the Huang Bai
      100 mg/kg (354.00 +/- 31.1 MUm/day), rhGH (367.10 +/- 27.11 MUm/day), and
      triptorelin (374.50 +/- 25.37 MUm/day) groups. Expression of IGF-1 and BMP-2 in
      the hypertrophic zone was higher in all experimental groups. Vaginal opening
      occurred earlier in the estradiol group (PND 33.58 +/- 1.62) than in controls and
      later in the triptorelin group (PND > 43). Ovarian and uterine weights were lower
      in the oestradiol and triptorelin groups. However, Huang Bai had nonsignificant
      effects on vaginal opening and the weights of ovaries and the uterus.
      Conclusions: Huang Bai stimulated bone growth by upregulating IGF-1 and BMP-2 in
      the growth plate. However, it had no effect on pubertal development.

PMID- 29344082
TI  - Implementing guidelines on physical health in the acute mental health setting: a
      quality improvement approach.
AB  - Background: In the UK, life expectancy for people living with a serious mental
      illness, such as schizophrenia and bipolar disorder, is reduced by 15-20 years
      compared with the general population. In recent years, evidence based
      guidelines/policies designed to improve their physical health have been
      published, yet a gap remains between recommendations and practice. This case
      study describes how guidelines to support physical health were implemented using
      a quality improvement approach. Case presentation: A quasi-experimental study
      explored systems and processes for assessing the physical health of patients
      admitted to an acute mental health unit. The multi-disciplinary team of
      healthcare professionals, service users and experts in quality improvement
      methods developed solutions to improve the assessment of physical health, drawing
      on existing guidelines/policies as well as professional and lived experience.
      Three key interventions were developed: a comprehensive physical health
      assessment; a patient-held physical health booklet; and education and training
      for staff and patients. Interventions were co-designed by front-line healthcare
      staff and service users with iterative development and implementation through
      Plan-Do-Study-Act cycles. Real-time weekly data were reported on five measures
      over a 15-month implementation period (318 patients) and compared to a 10-month
      baseline period (247 patients) to gauge the success of the implementation of the
      physical health assessment. Improvements were seen in the numbers of patients
      receiving a physical health assessment: 81.3% (201/247) vs 96.9% (308/318),
      recording of body mass index: 21.55% (53/247) vs 58.6% (204/318) and systolic
      blood pressure: 22.35% (55/247) vs 75.9% (239/318) but a reduction in the
      recording of smoking status: 80.1% (198/247) vs 70.9% (225/318). However, 31.7%
      (118/318) patients had a cardiovascular risk-score documented in the
      implementation phase, compared to none in the baseline. Conclusion: This study
      demonstrates the use of a quality improvement approach to support teams to
      implement guidelines on physical health in the acute mental health setting.
      Reflections of the team have identified the need for resources, training, support
      and leadership to support changes to the way care is delivered. Furthermore,
      collaborations between service users and frontline clinical staff can co-design
      interventions to support improvements and raise awareness of the physical health
      needs of this population.

PMID- 29344083
TI  - Psychosocial problems in traumatized refugee families: overview of risks and some
      recommendations for support services.
AB  - This article is an abridged version of a report by an advisory council to the
      German government on the psychosocial problems facing refugee families from war
      zones who have settled in Germany. It omits the detailed information contained in
      the report about matters that are specific to the German health system and asylum
      laws, and includes just those insights and strategies that may be applicable to
      assisting refugees in other host countries as well. The focus is on understanding
      the developmental risks faced by refugee children when they or family members are
      suffering from trauma-related psychological disorders, and on identifying
      measures that can be taken to address these risks. The following recommendations
      are made: recognizing the high level of psychosocial problems present in these
      families, providing family-friendly living accommodations, teaching positive
      parenting skills, initiating culture-sensitive interventions, establishing
      training programs to support those who work with refugees, expanding the
      availability of trained interpreters, facilitating access to education and health
      care, and identifying intervention requirements through screening and other
      measures.

PMID- 29344084
TI  - The Strengths and Difficulties Questionnaire (SDQ) in Africa: a scoping review of
      its application and validation.
AB  - Background: Child and adolescent mental health in Africa remains largely
      neglected. Quick and cost-effective ways for early detection may aid early
      intervention. The Strengths and Difficulties Questionnaire (SDQ) is globally used
      to screen for mental health problems, but little is known about its use in
      Africa. We set out to perform a scoping review to examine existing studies that
      have used the SDQ in Africa. Methods: A comprehensive scoping review methodology
      was used to identify all peer-reviewed studies ever published that have used the
      SDQ in Africa. Data were extracted and analysed to assess the countries,
      languages and SDQ versions used, the purpose of the SDQ studies, psychometric
      properties of the SDQ, and to consider knowledge gaps for future in-country and
      cross-country studies. Results: Fifty-four studies from 12 African countries were
      identified, most from South Africa. Many different languages were used, but
      authorized SDQs in those languages were not always available on the SDQinfo
      website. Authors frequently commented on challenges in the translation and
      backtranslation of mental health terminology in African languages. The SDQ was
      typically used to investigate internalisation/externalization disorders in
      different clinical populations, and was most frequently used in the evaluation of
      children and adolescents affected by HIV/AIDS. Sixteen studies (29.6%)
      administered the SDQ to participants outside the intended age range, only 4
      (7.4%) used triangulation of all versions to generate assessments, and eight
      studies (14.8%) used only subscales of the SDQ. Only one study conducted thorough
      psychometric validation of the SDQ, including examination of internal consistency
      and factor analysis. Where 'caseness' was defined in studies, UK cut-off scores
      were used in all but one of the studies. Conclusions: The SDQ may be a very
      useful tool in an African setting, but the scoping review suggested that, where
      it was used in Africa researchers did not always follow instrument guidelines,
      and highlighted that very little is known about the psychometric properties of
      the SDQ in Africa. We recommend comprehensive evaluation of the psychometric
      properties of the SDQ in various African languages, including internal
      consistency, factor structure, need for local cut-off values and ensuring
      cultural equivalence of the instrument.

PMID- 29344086
TI  - Correlation of structure, function and protein dynamics in GH7 cellobiohydrolases
      from Trichoderma atroviride, T. reesei and T. harzianum.
AB  - Background: The ascomycete fungus Trichoderma reesei is the predominant source of
      enzymes for industrial conversion of lignocellulose. Its glycoside hydrolase
      family 7 cellobiohydrolase (GH7 CBH) TreCel7A constitutes nearly half of the
      enzyme cocktail by weight and is the major workhorse in the cellulose hydrolysis
      process. The orthologs from Trichoderma atroviride (TatCel7A) and Trichoderma
      harzianum (ThaCel7A) show high sequence identity with TreCel7A, ~ 80%, and
      represent naturally evolved combinations of cellulose-binding tunnel-enclosing
      loop motifs, which have been suggested to influence intrinsic cellobiohydrolase
      properties, such as endo-initiation, processivity, and off-rate. Results: The
      TatCel7A, ThaCel7A, and TreCel7A enzymes were characterized for comparison of
      function. The catalytic domain of TatCel7A was crystallized, and two structures
      were determined: without ligand and with thio-cellotriose in the active site.
      Initial hydrolysis of bacterial cellulose was faster with TatCel7A than either
      ThaCel7A or TreCel7A. In synergistic saccharification of pretreated corn stover,
      both TatCel7A and ThaCel7A were more efficient than TreCel7A, although TatCel7A
      was more sensitive to thermal inactivation. Structural analyses and molecular
      dynamics (MD) simulations were performed to elucidate important
      structure/function correlations. Moreover, reverse conservation analysis (RCA) of
      sequence diversity revealed divergent regions of interest located outside the
      cellulose-binding tunnel of Trichoderma spp. GH7 CBHs. Conclusions: We
      hypothesize that the combination of loop motifs is the main determinant for the
      observed differences in Cel7A activity on cellulosic substrates. Fine-tuning of
      the loop flexibility appears to be an important evolutionary target in
      Trichoderma spp., a conclusion supported by the RCA data. Our results indicate
      that, for industrial use, it would be beneficial to combine loop motifs from
      TatCel7A with the thermostability features of TreCel7A. Furthermore, one region
      implicated in thermal unfolding is suggested as a primary target for protein
      engineering.

PMID- 29344087
TI  - Determination of the native features of the exoglucanase Cel48S from Clostridium
      thermocellum.
AB  - Background: Clostridium thermocellum is considered one of the most efficient
      natural cellulose degraders because of its cellulosomal system. As the major
      exoglucanase of cellulosome in C. thermocellum, Cel48S plays key roles and
      influences the activity and features of cellulosome to a great extent. Thus, it
      is of great importance to reveal the enzymatic features of Cel48S. However,
      Cel48S has not been well performed due to difficulties in purifying either
      recombinant or native Cel48S proteins. Results: We observed that the soluble
      fraction of the catalytic domain of Cel48S (Cel48S_CD) obtained by heterologous
      expression in Escherichia coli and denaturation-refolding treatment contained a
      large portion of incorrectly folded proteins with low activity. Using a
      previously developed seamless genome-editing system for C. thermocellum, we
      achieved direct purification of Cel48S_CD from the culture supernatant of C.
      thermocellum DSM1313 by inserting a sequence encoding 12 successive histidine
      residues and a TAA stop codon immediately behind the GH domain of Cel48S. Based
      on the fully active protein, biochemical and structural analyses were performed
      to reveal its innate characteristics. The native Cel48S_CD showed high activity
      of 117.61 +/- 2.98 U/mg and apparent substrate preference for crystalline
      cellulose under the assay conditions. The crystal structure of the native GH48
      protein revealed substrate-coupled changes in the residue conformation,
      indicating induced-fit effects between Cel48S_CD and substrates. Mass spectrum
      and crystal structural analyses suggested no significant posttranslational
      modification in the native Cel48S_CD protein. Conclusion: Our results confirmed
      that the high activity and substrate specificity of Cel48S_CD from C.
      thermocellum were consistent with its importance in the cellulosome. The
      structure of the native Cel48S_CD protein revealed evidence of conformational
      changes during substrate binding. In addition, our study provided a reliable
      method for in situ purification of cellulosomal and other secretive proteins from
      C. thermocellum.

PMID- 29344088
TI  - Incidence and root causes of delays in emergency orthopaedic procedures: a single
      centre experience of 36,017 consecutive cases over seven years.
AB  - Background: Emergency surgery is unplanned by definition and patients are
      scheduled for surgery with minimal preparation. Some patients who have sustained
      emergency orthopaedic trauma or other conditions must be operated on immediately
      or within a few hours, while others can wait until the hospital's resources
      permit and/or the patients' health status has been optimised as needed. This may
      affect the prioritisation procedures for both emergency and elective surgery and
      might result in waiting lists, not only for planned procedures but also for
      emergencies. Method: The main purpose of this retrospective, observational,
      single-centre study was to evaluate and describe for the number and reasons of
      delays, as well as waiting times in emergency orthopaedic surgery using data
      derived from the hospital's records and registers. All the emergency patients
      scheduled for emergency surgery whose procedures were rescheduled and delayed
      between 1 January 2007 and 31 December 2013 were studied. Result: We found that
      24% (8474) of the 36,017 patients scheduled for emergency surgeries were delayed
      and rescheduled at least once, some several times. Eighty per cent of these
      delays were due to organisational causes. Twenty-one per cent of all the delayed
      patients had surgery within 24 h, whilst 41% waited for more than 24 h, up to 3
      days. Conclusion: A large number of the clinic's emergency orthopaedic procedures
      were rescheduled and delayed and the majority of the delays were related to
      organisational reasons. The results can be interpreted in two ways; first,
      organisational reasons are avoidable and the potential for improvement is great
      and, secondly and most importantly, the delays might negatively affect patient
      outcomes.

PMID- 29344085
TI  - Synthesis, secretion, function, metabolism and application of natriuretic
      peptides in heart failure.
AB  - As a family of hormones with pleiotropic effects, natriuretic peptide (NP) system
      includes atrial NP (ANP), B-type NP (BNP), C-type NP (CNP), dendroaspis NP and
      urodilatin, with NP receptor-A (guanylate cyclase-A), NP receptor-B (guanylate
      cyclase-B) and NP receptor-C (clearance receptor). These peptides are genetically
      distinct, but structurally and functionally related for regulating circulatory
      homeostasis in vertebrates. In humans, ANP and BNP are encoded by NP precursor A
      (NPPA) and NPPB genes on chromosome 1, whereas CNP is encoded by NPPC on
      chromosome 2. NPs are synthesized and secreted through certain mechanisms by
      cardiomyocytes, fibroblasts, endotheliocytes, immune cells (neutrophils, T-cells
      and macrophages) and immature cells (embryonic stem cells, muscle satellite cells
      and cardiac precursor cells). They are mainly produced by cardiovascular, brain
      and renal tissues in response to wall stretch and other causes. NPs provide
      natriuresis, diuresis, vasodilation, antiproliferation, antihypertrophy,
      antifibrosis and other cardiometabolic protection. NPs represent body's own
      antihypertensive system, and provide compensatory protection to counterbalance
      vasoconstrictor-mitogenic-sodium retaining hormones, released by renin
      angiotensin-aldosterone system (RAAS) and sympathetic nervous system (SNS). NPs
      play central roles in regulation of heart failure (HF), and are inactivated
      through not only NP receptor-C, but also neutral endopeptidase (NEP), dipeptidyl
      peptidase-4 and insulin degrading enzyme. Both BNP and N-terminal proBNP are
      useful biomarkers to not only make the diagnosis and assess the severity of HF,
      but also guide the therapy and predict the prognosis in patients with HF. Current
      NP-augmenting strategies include the synthesis of NPs or agonists to increase NP
      bioactivity and inhibition of NEP to reduce NP breakdown. Nesiritide has been
      established as an available therapy, and angiotensin receptor blocker NEP
      inhibitor (ARNI, LCZ696) has obtained extremely encouraging results with
      decreased morbidity and mortality. Novel pharmacological approaches based on NPs
      may promote a therapeutic shift from suppressing the RAAS and SNS to re-balancing
      neuroendocrine dysregulation in patients with HF. The current review discussed
      the synthesis, secretion, function and metabolism of NPs, and their diagnostic,
      therapeutic and prognostic values in HF.

PMID- 29344089
TI  - Bone marrow failure may be caused by chromosome anomalies exerting effects on
      RUNX1T1 gene.
AB  - Background: The majority of the cases of bone marrow failure syndromes/aplastic
      anaemias (BMFS/AA) are non-hereditary and considered idiopathic (80-85%). The
      peripheral blood picture is variable, with anaemia, neutropenia and/or
      thrombocytopenia, and the patients with idiopathic BMFS/AA may have a risk of
      transformation into a myelodysplastic syndrome (MDS) and/or an acute myeloid
      leukaemia (AML), as ascertained for all inherited BMFS. We already reported four
      patients with different forms of BMFS/AA with chromosome anomalies as primary
      etiologic event: the chromosome changes exerted an effect on specific genes,
      namely RUNX1, MPL, and FLI1, leading to the disease. Results: We report two
      further patients with non-hereditary BM failure, with diagnosis of severe
      aplastic anaemia and pancytopenia caused by two different constitutional
      structural anomalies involving chromosome 8, and possibly leading to the disorder
      due to effects on the RUNX1T1 gene, which was hypo-expressed and hyper-expressed,
      respectively, in the two patients. The chromosome change was unbalanced in one
      patient, and balanced in the other one. Conclusions: We analyzed the sequence of
      events in the pathogenesis of the disease in the two patients, including a number
      of non-haematological signs present in the one with the unbalanced anomaly. We
      demonstrated that in these two patients the primary event causing BMFS/AA was the
      constitutional chromosome anomaly. If we take into account the cohort of 219
      patients with a similar diagnosis in whom we made cytogenetic studies in the
      years 2003-2017, we conclude that cytogenetic investigations were instrumental to
      reach a diagnosis in 52 of them. We postulate that a chromosome change is the
      primary cause of BMFS/AA in a not negligible proportion of cases, as it was
      ascertained in 6 of these patients.

PMID- 29344090
TI  - Overexpression of the proneural transcription factor ASCL1 in chronic lymphocytic
      leukemia with a t(12;14)(q23.2;q32.3).
AB  - Background: Translocations of the IGH locus on 14q32.3 are present in about 8% of
      patients with chronic lymphocytic leukemia (CLL) and contribute to leukemogenesis
      by deregulating the expression of the IGH-partner genes. Identification of these
      genes and investigation of the downstream effects of their deregulation can
      reveal disease-causing mechanisms. Case presentation: We report on the molecular
      characterization of a novel t(12;14)(q23.2;q32.3) in CLL. As a consequence of the
      rearrangement ASCL1 was brought into proximity of the IGHJ-CMU enhancer and was
      highly overexpressed in the aberrant B-cells of the patient, as shown by qPCR and
      immunohistochemistry. ASCL1 encodes for a transcription factor acting as a master
      regulator of neurogenesis, is overexpressed in neuroendocrine tumors and a
      promising therapeutic target in small cell lung cancer (SCLC). Its overexpression
      has also been recently reported in acute adult T-cell leukemia/lymphoma.To
      examine possible downstream effects of the ASCL1 upregulation in CLL, we compared
      the gene expression of sorted CD5+ cells of the translocation patient to that of
      CD19+ B-cells from seven healthy donors and detected 176 significantly
      deregulated genes (Fold Change >=2, FDR p <= 0.01). Deregulation of 55 genes in
      our gene set was concordant with at least two studies comparing gene expression
      of normal and CLL B-lymphocytes. INSM1, a well-established ASCL1 target in the
      nervous system and SCLC, was the gene with the strongest upregulation (Fold
      Change = 209.4, FDR p = 1.37E-4).INSM1 encodes for a transcriptional repressor
      with extranuclear functions, implicated in neuroendocrine differentiation and
      overexpressed in the majority of neuroendocrine tumors. It was previously shown
      to be induced in CLL cells but not in normal B-cells upon treatment with IL-4 and
      to be overexpressed in CLL cells with unmutated versus mutated IGHV genes. Its
      role in CLL is still unexplored. Conclusion: We identified ASCL1 as a novel IGH
      partner gene in CLL. The neural transcription factor was strongly overexpressed
      in the patient's CLL cells. Microarray gene expression analysis revealed the
      strong upregulation of INSM1, a prominent ASCL1 target, which was previously
      shown to be induced in CLL cells upon IL-4 treatment. We propose further
      investigation of the expression and potential role of INSM1 in CLL.

PMID- 29344091
TI  - The correlation between gain of chromosome 8q and survival in patients with clear
      and papillary renal cell carcinoma.
AB  - Background: The proto-oncogene c-MYC, located on chromosome 8q, can be
      upregulated through gain of 8q, causing alteration in biology of renal cell
      carcinoma (RCC). The aim of this study was to evaluate the prevalence of c-MYC
      through chromosome 8q gain and to correlate findings with cancer-specific
      mortality (CSM), and overall survival (OS). Methods: Cytogenetic analysis by
      conventional or Chromosomal Genomic Microarray Analysis (CMA) was performed on
      414 renal tumors. Nonclear and nonpapillary RCC were excluded. Impact of gain in
      chromosome 8q status on CSM, OS, and its correlation with clinicopathological
      variables were evaluated. CSM and OS were assessed using log-rank test and the
      Cox proportional hazards model. Results: A total of 297 RCC tumors with
      cytogenetic analysis were included. Gain of 8q was detected in 18 (6.1%) tumors
      (9 clear cell and 9 papillary RCC), using conventional method (n = 11) or CMA (n
      = 7). Gain of 8q was associated with higher T stage (p < 0.001), grade (p <
      0.001), nodal involvement (p = 0.005), and distant metastasis (p < 0.001). No
      association between gain of 8q and age (p = 0.23), sex (p = 0.46), and Charlson
      comorbidity index (CCI, p = 0.59) were seen. Gain of 8q was associated with an
      8.38-fold [95% confidence interval (CI), 3.83-18.34, p < 0.001] and 3.31-fold
      (95% CI, 1.56-7.04, p = 0.001) increase in CSM and decrease in OS, respectively,
      at a median follow up of 56 months. Conclusion: Chromosome 8q harbors the proto
      oncogene c-MYC, which can be upregulated by gain of 8q. Our findings suggest that
      gain of 8q, can predict aggressive tumor phenotype and inferior survival in RCC.

PMID- 29344092
TI  - Engaging the primary care community to encourage appropriate prostate cancer
      screening.
AB  - Prostate-specific antigen (PSA) screening for prostate cancer remains a
      controversial topic, particularly in the primary care community. Our
      multidisciplinary prostate screening panel at Duke University Health System, USA
      created a nuanced PSA screening algorithm, implemented it into the Electronic
      Health Record of Duke Primary Care, and conducted outreach meetings with primary
      care practices to support its rollout. Through this project, we identified areas
      of concern among primary care clinicians regarding PSA screening that we
      structured into two major categories: ideological opposition and logistical
      opposition. We outlined specific concerns in each major category and described
      how our team responded to those concerns. As communication between primary care
      clinicians and prostate specialists is vital to the success and safety of PSA
      screening programs, we hope that describing primary care concerns and our
      responses to them will help other health systems thoughtfully and efficiently
      implement appropriate PSA screening programs moving forward.

PMID- 29344093
TI  - Current best practice in the management of cystitis and pelvic pain.
AB  - Bladder pain syndrome (BPS) is a difficult disorder to diagnose and subsequently
      manage despite having been recognized for more than 200 years according to
      references in medical literature. There are currently three widely accepted
      guidelines on BPS: the American Urological Association Guidelines; the Royal
      College of Obstetricians and Gynaecologists in conjunction with the British
      Society of Urogynaecologists Guidelines; and the European Association of Urology
      Guidelines. These guidelines have similarities to each other but also significant
      differences. This leaves clinicians still confused about this condition and how
      to appropriately manage the 'real' patient. We review the current guidelines and
      appropriate literature and put forward a clinically usable management strategy.

PMID- 29344094
TI  - Robotic prostatectomy leading to a delayed MRSA infected lymphocele: a case
      report and review of the literature.
AB  - Prostate cancer is the second leading cancer-related cause of death in the USA
      with the majority presenting as localized disease. In the last decade minimally
      invasive, robotic-assisted laparascopic, radical prostatectomy has become the
      most favored treatment choice. A complication that has been observed in 27% of
      patients is the formation of an asymptomatic lymphocele. It is a very rare
      complication for these to become infected, and when they do 80% have occurred 2
      12 months post-procedure. In this case report the patient presented with fever
      and leukocytosis of unknown origin and was found to have a methicillin-resistant
      Staphylococcus aureus (MRSA) infected lymphocele over 2 years after a radical
      prostatectomy. The infected fluid collection was drained percutaneously and the
      patient was treated with a 4-week course of intravenous ceftaroline with complete
      resolution of symptoms.

PMID- 29344095
TI  - Metachronous metastasis of renal cell carcinoma to the urinary bladder: a case
      report.
AB  - We report a case of intravesical metastasis of a clear cell renal cell carcinoma.
      In renal cell carcinoma 16% of patients present with metastatic disease. Renal
      cell carcinoma can metastasize to nearly every organ, although metastatic spread
      to the urinary bladder is rare, with fewer than 70 described cases. The route and
      pattern of metastatic spread is not yet fully understood and different pathways
      are suggested. Gross haematuria is the presenting symptom in the majority of
      cases. These intravesical metastases may be synchronous or metachronous and can
      be solitary or part of polymetastatic disease. No standard treatment can be
      suggested due to the rare nature of this phenomenon, and treatment varies from
      transurethral resection, partial or complete cystectomy to systemic therapy.
      Prognosis in patients with a solitary bladder lesion that developed
      metachronously is rather good, whereas poor prognosis can be expected in patients
      with synchronous and multiple metastases.

PMID- 29344096
TI  - Prevention is better than cure: The role of infection prevention in the control
      of antimicrobial resistance.

PMID- 29344097
TI  - Investigating the use of an electronic hand hygiene monitoring and prompt device:
      influence and acceptability.
AB  - Introduction: Hand hygiene (HH) prevents the transmission of healthcare
      associated infections. Electronic HH monitoring and prompt devices have been
      developed to overcome problems with monitoring HH and to improve compliance.
      Devices monitor room entry and exit and soap use through communication between
      ceiling sensors and badges worn by practitioners and the badges sense alcohol
      rub. Objectives: To investigate (1) the impact of devices on HH compliance, (2)
      how devices influence behaviour and (3) the experience and opinions of
      practitioners on the use devices. Methods: HH compliance was monitored (before,
      during and after system installation) by observations and alcohol rub usage.
      Compliance during installation was also monitored by the device. Healthcare
      practitioner interviews (n = 12) explored how the device influenced behaviour and
      experiences and opinions of wearing the device. Results: HH compliance improved
      during the period the device was installed. Practitioners reported the device
      increased their awareness, enhancing their empathy for patients and encouraged
      patients and colleagues to prompt when HH was needed. Practitioners' reported
      better HH, gaming the system and feelings of irritation. Conclusion: HH prompt
      and monitoring systems seem to improve compliance but improvements may be
      undermined by practitioner irritation and system gaming.

PMID- 29344098
TI  - 'Time to clean': A systematic review and observational study on the time required
      to clean items of reusable communal patient care equipment.
AB  - Background: Concerns have been raised over poor standards of hospital cleanliness
      and insufficient time for staff to clean reusable communal patient care
      equipment. These items may then act as vectors for the transmission of nosocomial
      pathogens between hospital patients. Aim: To evaluate the impact of cleaning
      duration on nosocomial infection rates and estimate the time required to clean
      care equipment in accordance with national specifications (i.e. a 'time to
      clean'). Methods: A systematic review of the published literature on cleaning
      times and an observational study in which nine healthcare workers cleaned seven
      items of care equipment while the duration of time taken to clean each item was
      measured. Results: A limited volume of low-quality evidence indicates that
      increased cleaning times in hospitals can reduce the incidence of healthcare
      associated infections (HCAIs). The mean 'time to clean' for care equipment ranged
      from 166.3 s (95% confidence interval [CI] = 117.8-214.7) for a bed frame to 29.0
      s (95% CI = 13.4-44.6) for a blood pressure cuff. Discussion: 'Time to clean'
      estimates for care equipment provide an indication of how much protected time is
      necessary to ensure acceptable standards of cleanliness. Clinical trials are
      needed to further evaluate the impact of increased cleaning times on nosocomial
      infection rates.

PMID- 29344099
TI  - Audit of the management of patients at high risk of carbapenemase-producing
      enterobacteriaceae (CPE): Are we ready?
AB  - Background: Incidence of carbapenemase-producing enterobacteriaceae (CPE) in the
      UK is increasing. In 2013, Public Health England (PHE) published a toolkit to
      control spread of CPE within healthcare settings. Aim: To assess compliance to
      hospital CPE policy (adapted from PHE) in the identification, isolation and
      screening of suspected CPE patients. Methods: Admission booklets of 150 patients
      were evaluated to see whether the relevant section had been completed to identify
      high-risk CPE patients. Where necessary, patients were interviewed or their GPs
      were contacted to assess their CPE risk. Additionally, 28 patients screened for
      CPE were audited to assess compliance to screening and isolation. Findings: Only
      23 patients out of 147 (15.6%) were risk assessed on admission. Risk status of 27
      (18.4%) patients could not be assessed due to lack of data. Fifteen patients out
      of 28 (54%) screened for CPE were identified and isolated on admission. Ten out
      of 19 patients (53%) had three screens 48 h apart. Discussion: This audit
      highlights difficulties in screening based on individual risk factors as the
      majority of patients were not screened on admission and documentation on
      isolation and screening was poor. More needs to be done to raise awareness of the
      requirements for routine assessment, isolation and screening.

PMID- 29344100
TI  - Surgical site infection prevention: An analysis of compliance with good practice
      in a teaching hospital.
AB  - Background: Surgical teams play a critical role in reducing surgery-related risks
      during preoperative and intraoperative phases. Aim: To analyse the preoperative
      and intraoperative practices adopted by surgical teams in surgical site
      infections prevention. Methods: This was a cross-sectional study conducted during
      April-September 2013 in a large university hospital in Belo Horizonte, Minas
      Gerais, Brazil. It was conducted through observation of the surgical practice
      during preoperative and intraoperative phases of procedures used by a
      gastroenterological, cardiovascular and paediatric surgical team. Results: A
      total of 100 surgeries were monitored. Hair removal was performed for 20% of the
      patients inside the operating room by professionals using clippers in 65% of
      operations. The antimicrobial agent of choice was appropriate/satisfactory in 62%
      of the operations and administered up to 60 min before surgical incision in 90.3%
      of the cases. The operating room door was kept closed in 4% of these procedures.
      Discussion: Some preoperative measures for surgical site infection prevention
      were not adhered to by the professionals who were monitored in this study. It is
      recommended that surgical teams undergo professional surveillance and training to
      highlight the necessity and importance of implementing measures to improve the
      quality of care provided to surgical patients.

PMID- 29344101
TI  - Healthcare-associated Legionnaires' disease: Limitations of surveillance
      definitions and importance of epidemiologic investigation.
AB  - Healthcare-associated Legionnaires' disease (HCA LD) causes significant morbidity
      and mortality, with varying guidance on prevention. We describe the evaluation of
      a case of possible HCA LD and note the pitfalls of relying solely on an
      epidemiologic definition for association of a case with a facility. Our detailed
      investigation led to the identification of a new Legionella pneumophila serogroup
      1 sequence type, confirmed a healthcare association and helped build the
      framework for our ongoing preventive efforts. Our experience highlights the role
      of routine environmental cultures in the assessment of risk for a given facility.
      As clinicians increasingly rely on urinary antigen testing for the detection of
      L. pneumophila, our investigation emphasises the importance of clinical cultures
      in an epidemiologic investigation.

PMID- 29344103
TI  - Diary.

PMID- 29344102
TI  - Should preoperative showering or cleansing with chlorhexidine gluconate (CHG) be
      part of the surgical care bundle to prevent surgical site infection?
AB  - Showering preoperatively with chlorhexidine gluconate is an issue that continues
      to promote debate; however, many studies demonstrate evidence of surgical site
      infection risk reduction. Methodological issues have been present in many of the
      studies used to compile guidelines and there has been a lack of standardisation
      of processes for application of the active agents in papers pre-2009. This review
      and commentary paper highlights the potential for enhancing compliance with this
      low-risk and low-cost intervention and provides some guidance for enhancing
      implementation of preoperative showering with both chlorhexidine in solution and
      impregnated wipes.

PMID- 29344104
TI  - X-inactive-specific transcript of peripheral blood cells is regulated by exosomal
      Jpx and acts as a biomarker for female patients with hepatocellular carcinoma.
AB  - Background: Long noncoding ribonucleic acid (lncRNA) X-inactive-specific
      transcript (Xist) was reported to affect cell proliferation and metastasis in
      hepatocellular carcinoma (HCC). However, there are rare reports focusing on the
      diagnostic evaluation and regulatory mechanism of Xist expression from peripheral
      blood cells of patients with HCC. Methods: In this study, a cohort of 206 female
      participants including healthy volunteers (HVs) and patients with chronic
      hepatitis B (CHB), cirrhosis and HCC was recruited. Coculture system was used to
      evaluate the effects of exosomal JPX transcript, XIST activator (Jpx) on Xist
      expression of blood cells. Results: First, Xist expressions of both peripheral
      blood mononuclear cells and granulocytes were upregulated in female patients with
      HCC, and showed significantly increased discriminatory power when differentiating
      female patients with early-stage HCC from controls or differentiating female
      patients with HCC from patients with CHB and cirrhosis, compared with alpha
      fetoprotein (AFP). Then, another lncRNA Jpx that was an activator of Xist was
      upregulated in exosomes, mononuclear cells and granulocytes of female patients
      with HCC. Furthermore, our results showed that Jpx could be delivered from HCC
      cells to blood cells via exosomes and activate Xist expression of blood cells by
      repressing the transregulatory effects of CCCTC-binding factor (CTCF).
      Conclusions: This study revealed an exosome-mediated regulation of Xist
      expression in blood cells and suggested that Xist expressions of mononuclear
      cells and granulocytes would be promising biomarkers for diagnosis of female
      patients with HCC.

PMID- 29344105
TI  - Optimal duration of adjuvant endocrine therapy: how to apply the newest data.
AB  - Background: The benefit of 5 years of adjuvant endocrine therapy for women with
      hormone receptor-positive (HR+) breast cancer (BC) is beyond discussion.
      Nevertheless, the risk of recurrence of luminal BC persists for 15 years or more
      after diagnosis. Consequently, approaches of extended adjuvant therapy have been
      investigated in large clinical trials, with the ultimate aim of further reducing
      the risk of recurrence in patients with HR+ BC. Methods: A review of recently
      published trial data is presented to provide a solid basis for discussion. A
      discussion of the side effects of long-term endocrine treatment, multigenetic
      tests aiming to identify patients at particular risk, and an outlook for further
      promising targets are additional aims of this review. Conclusion: Extended
      adjuvant therapy seems beneficial in reducing distant relapse and contralateral
      BC for a selected group of patients with HR+ BC, particularly if aromatase
      inhibitors (AIs) are used after initial tamoxifen therapy. However, patients with
      lower risk of recurrence and initial AI therapy may suffer more from side effects
      than benefit from extended therapy.

PMID- 29344106
TI  - Overall survival and progression-free survival with endocrine therapy for hormone
      receptor-positive, HER2-negative advanced breast cancer: review.
AB  - We reviewed randomized phase II/III trials comparing first- or second-line
      endocrine therapy as monotherapy or in combination with targeted therapies for
      treatment of postmenopausal patients with hormone receptor-positive advanced
      breast cancer. First-line was defined as treatment for endocrine therapy-naive
      advanced breast cancer or advanced disease treated with endocrine therapy in the
      adjuvant/neoadjuvant setting. Second-line was defined as endocrine therapy for
      advanced breast cancer following disease progression on endocrine therapy for
      advanced disease. Publications reporting progression-free survival (PFS)/time to
      progression (TTP) or overall survival (OS) for FDA-approved agents anastrozole,
      exemestane, fulvestrant 250 mg, fulvestrant 500 mg, letrozole (0.5 and 2.5 mg),
      megestrol acetate, and tamoxifen as monotherapy, or in combination with
      everolimus, palbociclib or ribociclib, were assessed. First-line monotherapy with
      anastrozole, fulvestrant 500 mg or letrozole 2.5 mg significantly improved
      PFS/TTP versus comparator endocrine therapy; however, only fulvestrant 500 mg
      improved OS. For endocrine therapy in combination with targeted therapies,
      palbociclib plus letrozole 2.5 mg, and ribociclib plus letrozole 2.5 mg
      significantly improved PFS versus letrozole 2.5 mg alone first-line. For second
      line monotherapies, exemestane, fulvestrant 500 mg and letrozole 2.5 mg
      significantly improved PFS/TTP versus comparator endocrine therapy; only
      fulvestrant 500 mg and letrozole 2.5 mg improved OS. For second-line combination
      therapies, everolimus plus exemestane, and palbociclib plus fulvestrant 500 mg,
      improved PFS versus endocrine therapy alone. In both first- and second-line
      settings, aromatase inhibitors demonstrated PFS benefits versus comparator
      endocrine therapy; however, fulvestrant 500 mg was the only endocrine therapy
      included in our review to show both PFS and OS advantages compared with other
      endocrine therapies. Targeted agents in combination with endocrine therapy have
      demonstrated PFS improvements both first- and second-line; OS data are awaited.

PMID- 29344107
TI  - Managing hyponatremia in lung cancer: latest evidence and clinical implications.
AB  - Hyponatremia is the most common electrolyte disorder in lung cancer patients.
      This condition may be related to many causes including incidental medications,
      concurrent diseases and side effects of antineoplastic treatments or the disease
      itself. Although not frequently life-threatening, it is usually associated with
      prolonged hospitalization, delays in scheduled chemotherapy, worsening of patient
      performance status and quality of life and may also negatively affect treatment
      response and survival. Most of the available data focus on thoracic tumors,
      especially small-cell lung cancer (SCLC), where hyponatremia is frequently
      related to the syndrome of inappropriate secretion of antidiuretic hormone
      (SIADH). Few studies specifically focus on non-small cell lung cancer (NSCLC)
      patients. Hyponatremia treatment needs to be personalized based on severity and
      duration of sodium serum reduction, extracellular fluid volume and etiology.
      However, literature data highlight the importance of early correction of the
      serum concentration levels. To achieve this the main options are fluid
      restriction, hypertonic saline, loop diuretics, isotonic saline, tolvaptan and
      urea. The aim of this review is to analyze the role of hyponatremia in lung
      cancer patients, evaluating causes, diagnosis, management and clinical
      implications.

PMID- 29344109
TI  - Corrigendum.
AB  - [This corrects the article DOI: 10.1177/1758834017711097.].

PMID- 29344108
TI  - Estimating the 95% confidence interval for survival gain between an experimental
      anti-cancer treatment and a control.

PMID- 29344111
TI  - Corrigendum.
AB  - [This corrects the article DOI: 10.1177/1759720X17729641.].

PMID- 29344110
TI  - Anti-interleukin and interleukin therapies for psoriasis: current evidence and
      clinical usefulness.
AB  - Anti-interleukin (IL) therapies have emerged as a major treatment for patients
      with moderate-to-severe psoriasis. This article reviews the up-to-date results of
      pivotal clinical trials targeting the interleukins used for the treatment of
      psoriasis, including IL-1, IL-2, IL-6, IL-8, IL-10, IL-12, IL-17, IL-20, IL-22,
      IL-23, IL-36 and bispecific biologics IL-17A/tumor necrosis factor alpha (TNF
      alpha). Cytokines involved in the circuits of psoriasis inflammation without
      ongoing clinical trials are also mentioned (IL-9, IL-13, IL-15, IL-16, IL-18, IL
      19, IL-21, IL-24, IL-27, IL-33, IL-35, IL-37, and IL-38).

PMID- 29344112
TI  - ZGDHu-1 for cancer therapy.
AB  - N,N'-di-(m-methylphenyl)-3,6-dimethyl-1,4-dihydro-1,2,4,5-tetrazine-1,4
      dicarboamide (ZGDHu-1) is a novel tetrazine derivative that was initially
      designed and produced by Professor W.X. Hu, and which has been reported by our
      group to exhibit antitumor activity. Accumulating evidence suggests that the
      anticancer mechanisms of ZGDHu-1 may be involved indifferent biological
      activities, particularly in acute myeloid leukemia (AML) cells. At a high
      concentration, ZGDHu-1 has been demonstrated to inhibit the proliferation of the
      leukemia cells by arresting the cell cycle at the G2/M phase, and by inducing
      cell apoptosis via inducing the accumulation of reactive oxygen species, the
      translocation of phosphatidylserine across the plasma membrane and the loss of
      mitochondrial membrane potential. Furthermore, at a low concentration, it was
      demonstrated to induce the differentiation and degrade the AML1-eight-twenty-one
      fusion protein in AML cells. Finally, results from a previous study indicate that
      ZGDHu-1 is a potential proteasome inhibitor. Overall, our preliminary research
      suggests that ZGDHu-1 may be a promising anticancer drug; however, further
      research is warranted to identify the exact drug target and potential clinical
      application in leukemia cells or solid tumors. In the present review, the
      application of ZGDHu-1 in cancer research, in addition to the specific underlying
      targets of ZGDHu-1, are discussed.

PMID- 29344113
TI  - Downregulated miRNA-1269a variant (rs73239138) decreases the susceptibility to
      gastric cancer via targeting ZNF70.
AB  - Although emerging evidence has indicated that single nucleotide polymorphisms
      (SNPs) in microRNAs (miRNAs) are associated with susceptibility to gastric
      cancer, a limited number of studies have revealed the underlying molecular
      mechanisms. In the present study, the results suggested that miR-1269a rs73239138
      has a role in decreasing the risk of gastric cancer. The level of miR-1269a
      variant expression was significantly downregulated compared with the wild-type
      miR-1269a in the gastric cells (Fig. 1). Furthermore, overexpression of miR-1269a
      inhibited apoptosis of gastric cancer cells. Expression of the miR-1269a variant
      inhibited the function of miR-1269a by increasing the apoptotic rate and the
      expression of Bik, Bim and Bak was upregulated consistently. In addition, zinc
      finger protein 70 (ZNF70) was identified to be a target gene of miR-1269a, which
      was downregulated by miR-1269a and upregulated by miR-1269a variant. ZNF70 was
      indicated to exert a role as a tumor suppressor in gastric cancer. To the best
      our knowledge, the present study for the first time highlights a critical role of
      miR-1269a variant rs73239138 in decreasing the susceptibility to gastric cancer
      by downregulating its expression and targeting ZNF70, which promotes apoptosis of
      gastric cancer cells. This SNP is indicated to serve as a potential biomarker and
      therapeutic target for gastric cancer.

PMID- 29344114
TI  - HNF-4alpha promotes multidrug resistance of gastric cancer cells through the
      modulation of cell apoptosis.
AB  - Multidrug resistance (MDR) typically leads to treatment failure, and is
      associated with disease progression of gastric cancer (GC). In the present study,
      a total of 15 aberrantly activated transcription factors (TFs) were detected in
      chemo-resistant GC cells using a TF Activation Profiling Plate Array. Among these
      TFs, hepatocyte nuclear factor (HNF)-4alpha was significantly upregulated in
      multidrug-resistant GC cells (P=0.019). The overexpression of HNF-4alpha was able
      to cause resistance to multiple chemotherapeutics, whereas inhibition of HNF
      4alpha appeared to reverse cancer cell resistance. Further studies demonstrated
      that HNF-4alpha had no clear influence on drug transportation; however,
      inhibition of drug-induced cell apoptosis occurred as B-cell lymphoma 2 (Bcl-2)
      expression increased in GC cells. Additionally, immunohistochemistry demonstrated
      that HNF-4alpha was overexpressed in human GC tissues, and associated with tumor
      stage and lymph node metastasis. In conclusion, the results of the present study
      indicate the involvement of TFs in MDR in GC, and suggest that HNF-4alpha may
      enhance MDR in GC by regulating cell apoptosis and Bcl-2 expression.

PMID- 29344115
TI  - Clinical significance of LMO1 in gastric cancer tissue and its association with
      apoptosis of cancer cells.
AB  - It has been reported that LMO1 gene was associated with progression, metastasis
      and apoptosis of leukemia, colorectal cancer and lung cancer. However, the
      association of LMO1 and gastric cancer remains unclear. The aim of this study is
      to analyze the relation between LMO1 expression and apoptosis of gastric cancer
      cells and explore the clinical implications of LMO1 in gastric cancer tissues.
      The results demonstrated that expression levels of LMO1 and Bcl-2 proteins in
      gastric cancer tissues were higher than those in adjacent tissues, whereas the
      opposite was detected for Bax expression (P<0.05). LMO1 protein was associated
      with TNM staging and lymph node metastasis in gastric cancer (P<0.05). The
      survival rate of the patients with positive LMO1 gastric carcinoma was lower than
      that with negative LOM1 expression, and LMO1 was as an independent prognostic
      factor in COX survival analysis (P<0.05). LMO1-siRNA transfected MKN45 cells had
      a significant decrease in LMO1 expression and the cell viability, despite of an
      increase in the apoptotic rate (P<0.05). Following LMO1-siRNA transfection, Bcl-2
      expression decreased, while the expression of Bax increased (P<0.05). It's
      concluded that overexpressed LMO1 in gastric cancer could be as one of new
      markers of poor prognosis.

PMID- 29344116
TI  - Knockdown of TGIF attenuates the proliferation and tumorigenicity of EC109 cells
      and promotes cisplatin-induced apoptosis.
AB  - A previous study has reported that frequent amplifications of the TG-interacting
      factor (TGIF) were observed in esophageal squamous cell carcinoma. The aim of the
      present study was to investigate the potential role of TGIF in the proliferation
      and tumorigenicity of the esophageal cancer cell line EC109 and cisplatin-induced
      apoptosis. Stable TGIF-knockdown EC109 cell line was established by infecting
      short hairpin RNA (shRNA) lentiviral particles. Soft agar and tumor xenograft
      assays were applied in nude mice. Flow cytometry was employed to evaluate the
      cell cycle and apoptosis. Western blot analysis was used to detect the expression
      of proteins. TGIF knockdown suppressed EC109 cell proliferation, colony formation
      in soft agar and tumor growth in nude mice, induced cell cycle arrest in the G1
      phase, and promoted cisplatin-induced apoptosis. In addition, TGIF knockdown
      significantly reduced the expression of phospho-Rb in EC109 cells. The reduced
      level of full length PARP expression and the increased level of cleaved caspase-3
      expression were observed in EC109 cells with the treatment of cisplatin and TGIF
      knockdown. The results suggest that knockdown of TGIF attenuated the
      proliferation and tumorigenicity of EC109 cells, and promoted cisplatin-induced
      apoptosis.

PMID- 29344117
TI  - Wnt inhibitor XAV939 suppresses the viability of small cell lung cancer NCI-H446
      cells and induces apoptosis.
AB  - Small cell lung cancer (SCLC) is the most aggressive type of lung cancer due to a
      fast tumor doubling time and early hematogenous spread. Advances in the treatment
      of non-small cell lung cancer using targeted therapies having been made, but no
      targeted drugs for SCLC have been approved. The Wnt signaling pathway is
      associated with tumor progression and metastasis; therefore, the inhibition of
      Wnt/beta-catenin signaling is a strategy for anticancer drugs. Tankyrase 1
      (TNKS1) is overexpressed in a number of types of cancer and XAV939 is a small
      molecule inhibitor of TNKS1 which may inhibit tumor growth. The present study
      aimed to investigate the potential molecular mechanisms underlying XAV939-induced
      suppression of the viability of SCLC cells. MTT assays were used to determine the
      viability-inhibition rate of cells and to identify the drug concentration which
      optimally inhibited cell viability. Flow cytometry was used to determine whether
      XAV939 induced apoptosis of SCLC cells, and to analyze the effect of the drug on
      the cell cycle. The results of the present study identified that XAV939 inhibited
      the viability of NCI-H446 cells in a dose-dependent manner, but cisplatin
      inhibited NCI-H446 cell viability in a time- and dose-dependent manner. The
      combination of XAV939 and cisplatin exhibited a slightly more pronounced
      inhibition of cell viability at an increased dose of XAV939. In addition, XAV939
      markedly induced cell apoptosis of the SCLC cell line H446 by increasing the
      proportion of cells in the G0/G1 phase, leading to inhibition of the cell cycle.
      The results of the present study indicated that XAV939 inhibited the viability of
      the NCI-H446 SCLC cell line by inducing cell apoptosis through the Wnt signaling
      pathway. Therefore, XAV939 may be useful for the treatment of SCLC.

PMID- 29344118
TI  - SHISA2 enhances the aggressive phenotype in prostate cancer through the
      regulation of WNT5A expression.
AB  - The present study aimed at identifying novel molecular cancer drug targets and
      biomarkers by analyzing the gene expression profiles of high-grade prostate
      cancer (PC), using a cDNA microarray combined with laser microbeam
      microdissection. A number of genes were identified that were transactivated in
      high-grade PC. First, a novel molecular target and diagnostic biomarker, shisa
      family member 2 (SHISA2), was identified as an overexpressed gene in high-grade
      PC cells. The reverse transcription-semi-quantitative polymerase chain reaction
      and immunohistochemical analysis validated the overexpression of SHISA2 (295
      amino acids in length), specifically in high-grade PC cells with Gleason scores
      of between 8 and 10, relative to normal prostate epithelium. Knockdown of SHISA2
      expression by short interfering RNA resulted in the marked suppression of PC cell
      viability. By contrast, exogenous SHISA2 expression in transfected cells promoted
      PC cell proliferation, indicating its oncogenic effects. Notably, as a result of
      cDNA microarray analysis, protein Wnt-5a (WNT5A) was focused upon and the
      expression of WNT5A was identified to be downregulated in SHISA2-knockdown.
      Western blot analysis validated significant downregulation of WNT5A by SHISA2
      knockdown and upregulation of WNT5A by SHISA2 overexpression. The results of the
      present study indicated that SHISA2 may affect WNT5A synthesis. Furthermore, the
      secreted SHISA2 protein was determined in the culture medium of PC cells. We
      hypothesize that SHISA2 is involved in the regulation of WNT5A and in the
      aggressiveness of PC via the Wnt signaling pathway through WNT5A. Furthermore,
      SHISA2 may be a molecular target for cancer drugs, and a useful diagnostic
      biomarker for the prognosis and therapeutic effect in cancer.

PMID- 29344119
TI  - Effect of Lipodox in combination with bevacizumab in a patient with a metastatic
      malignant phyllodes breast tumor: A case report.
AB  - A 76-year-old female patient with a malignant phyllodes tumor underwent modified
      radical mastectomy and wide excision. Multiple nodules were observed in the
      operated wound area. Positron emission tomography-computed tomography (PET-CT)
      revealed recurrent disease in the left breast, the adjacent left third rib, the
      left internal mammary region and the left ilium. A novel formulation of
      bevacizumab (5 mg/m2, first day) in combination with liposomal doxorubicin
      (Lipodox, 30 mg/m2, second day) was administered for 3 cycles every 2 weeks, and
      subsequently wide excision was performed. Lipodox (40 mg/m2) was administered for
      3 cycles every 3 weeks, starting 4 weeks after the surgery. Follow-up whole body
      PET-CT scanning, 3 and 6 months later, indicated no sign of residual
      hypermetabolic malignancy. Malignant phyllodes tumors do not usually respond to
      chemotherapy or radiotherapy. In the present case report, a novel formulation of
      bevacizumab in combination with Lipodox was administered as neoadjuvant
      chemotherapy in a patient with a malignant phyllodes tumor and preoperative tumor
      shrinkage was achieved, resulting in clear resection margins.

PMID- 29344120
TI  - Interim 18F-FDG PET/CT improves the prognostic value of S-IPI, R-IPI and NCCN-IPI
      in patients with diffuse large B-cell lymphoma.
AB  - The current study aimed to explore whether the efficiency of the standard
      International Prognostic Index (S-IPI), revised-IPI (R-IPI) and enhanced-IPI
      (NCCN-IPI) in evaluating the prognosis of patients with diffuse large B-cell
      lymphoma (DLBCL) may be improved by interim 18F-FDG PET/CT. A total of 185
      patients with newly diagnosed DLBCL were enrolled in the current study. All
      patients underwent interim PET/CT following the 4th cycle of chemotherapy.
      Patients were divided into different risk groups using S-IPI, R-IPI and NCCN-IPI
      and further subdivided into risk groups using interim PET/CT. Interpretations
      were evaluated for 2-year progression-free survival (PFS) and overall survival
      (OS). With a median follow-up time of 44 months, the 2-year PFS and OS were 60%
      [95% confidence interval (CI) 53-67%] and 81% (95% CI 74-86%), respectively.
      Analysis of S-IPI and NCCN-IPI identified no significant difference in PFS and OS
      between high intermediate and high risk groups. However, there were significant
      differences in the PFS and OS between the low and low intermediate risk groups
      (P<0.01). Interim PET/CT was used to redistribute patients in the higher risk
      group into PET negative and positive groups (P<0.01) and arallel results were
      observed in the lower risk group. In R-IPI, interim PET/CT identified a
      significant difference between PFS and OS in the good and poor risk groups but
      not in the very good risk group. Therefore, the results of the current study
      indicate that S-IPI, R-IPI and NCCN-IPI are three clinically useful prognostic
      indexes for patients with DLBCL. Interim PET/CT may improve the prognostic value
      of S-IPI, R-IPI and NCCN-IPI in predicting 2-year PFS and OS, particularly in
      patients with a high IPI score.

PMID- 29344121
TI  - A five-gene based risk score with high prognostic value in colorectal cancer.
AB  - Colorectal cancer (CRC) is one of the most frequently occurring malignancies
      worldwide. The outcomes of patients with similar clinical symptoms or at similar
      pathological stages remain unpredictable. This inherent clinical diversity is
      most likely due to the genetic heterogeneity. The present study aimed to create a
      predicting tool to evaluate patient survival based on genetic profile. Firstly,
      three Gene Expression Omnibus (GEO) datasets (GSE9348, GSE44076 and GSE44861)
      were utilized to identify and validate differentially expressed genes (DEGs) in
      CRC. The GSE14333 dataset containing survival information was then introduced in
      order to screen and verify prognosis-associated genes. Of the 66 DEGs, the
      present study screened out 46 biomarkers closely associated to patient overall
      survival. By Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway
      analysis, it was demonstrated that these genes participated in multiple
      biological processes which were highly associated with cancer proliferation, drug
      resistance and metastasis, thus further affecting patient survival. The five most
      important genes, MET proto-oncogene, receptor tyrosine kinase, carboxypeptidase
      M, serine hydroxymethyltransferase 2, guanylate cyclase activator 2B and sodium
      voltage-gated channel a subunit 9 were selected by a random survival forests
      algorithm, and were further made up to a linear risk score formula by
      multivariable cox regression. Finally, the present study tested and verified this
      risk score within three independent GEO datasets (GSE14333, GSE17536 and
      GSE29621), and observed that patients with a high risk score had a lower overall
      survival (P<0.05). Furthermore, this risk score was the most significant compared
      with other predicting factors including age and American Joint Committee on
      Cancer stage, in the model, and was able to predict patient survival
      independently and directly. The findings suggest that this survival associated
      DEGs-based risk score is a powerful and accurate prognostic tool and is
      promisingly implemented in a clinical setting.

PMID- 29344122
TI  - Inhibition of breast cancer cell growth by the Pteris semipinnata extract ent
      11alpha-hydroxy-15-oxo-kaur-16-en-19-oic-acid.
AB  - Previous studies have demonstrated strong anti-tumor effects of ent-11alpha
      hydroxy-15-oxo-kaur-16-en-19-oic-acid (5F), an extract from Pteris semipinnata,
      in liver, lung, stomach and anaplastic thyroid cancer cells. However, whether 5F
      inhibits the growth of breast cancer cells remains unclear. The present study
      assessed the effect of 5F on breast cancer cells. The breast cancer cell lines
      MCF-7, MDA-MB-231 and SK-BR-3 were each treated with 0, 5, 10, 20 and 40 ug/ml
      5F. Morphological changes in the breast cancer cells were assessed using
      fluorescence microscopy. The proliferation and apoptosis of the breast cancer
      cells were also examined using Cell Counting Kit-8 and flow cytometry. The levels
      of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X apoptosis regulator (Bax), Bcl-2
      antagonist/killer (Bak) 1 and caspase-3 in the breast cancer cells were assessed.
      The results of the present study demonstrated that 5F inhibited the proliferation
      of MCF-7, MDA-MB-231 and SK-BR-3 breast cancer cells in a concentration- and time
      dependent manner. Treatment with 5F also induced the apoptosis of breast cancer
      cells. MDA-MB-231, MCF-7, and SK-BR-3 cells exhibited apoptotic rates of 40.13,
      60.44, and 70.49%, respectively, following incubation with 5F for 24 h.
      Furthermore, 5F significantly decreased the expression of Bcl-2 and increased the
      expression of Bax, Bak, and caspase-3 in a concentration-dependent manner. The
      results of the present study revealed that the P. semipinnata extract 5F
      inhibited the growth of human breast cancer cells in a time- and concentration
      dependent manner, and that 5F induced apoptosis of human breast cancer cells.

PMID- 29344123
TI  - Ex vivo model of non-small cell lung cancer using mouse lung epithelial cells.
AB  - Lung cancer is the most common cause of cancer mortality, however, efficient
      methods to culture, expand and transform lung epithelial (LE) cells have not been
      established. In the present study, an efficient ex vivo method was applied to
      recapitulate lung carcinogenesis using mouse LE cells. A Matrigel-assisted three
      dimensional culture was used to isolate and selectively expand LE cells from
      mouse lungs. Purified LE cells were passaged and expanded for at least 2 to 3
      months while maintaining epidermal growth factor-dependence. LE cells were also
      easily transformed by genetic manipulations using retroviral vectors. A SV40
      large-T antigen, suppressing p53 and pRB, plus an activated oncogene, such as
      KrasG12V or EGFRex19del, were required to transform LE cells. Transformed cells
      formed tumors resembling non-small cell lung cancer (NSCLC) in allograft models
      and exhibited strong oncogene addiction. This experimental system provided a
      unique model system to study lung tumorigenesis and develop novel therapeutics
      against NSCLC.

PMID- 29344124
TI  - Molecular, biological characterization and drug sensitivity of chidamide
      resistant non-small cell lung cancer cells.
AB  - Chidamide, a histone deacetylase (HDAC) inhibitor, has been applied in clinical
      trials for various types of hematological and solid tumors. Although acquired
      resistance is common in chemotherapy, the mechanism of resistance to chidamide is
      poorly characterized. The goal of the present study was to explore, in detail,
      the mechanism for the induced resistance to chidamide, and investigate a
      potential cross-resistance to other chemotherapeutic drugs. A549 cells were
      exposed to gradually increasing chidamide concentrations to establish a chidamide
      resistant non-small cell lung cancer cell line (A549-CHI-R). The IC50 for
      chidamide, the proliferation inhibition rate, the total HDAC activity and the
      HDAC protein level were determined by an MTT assay, colony formation, a
      fluorometric HDAC activity assay and western blotting, respectively.
      Overexpression of the HDAC1 gene and HDAC1 gene-knockdown were achieved via
      plasmid transfection. A549-CHI-R cells demonstrated increased resistance to
      chidamide (8.6-fold). HDAC1 protein degradation was inhibited and HDAC activity
      was significantly higher in the A549-CHI-R cells relative to the parental A549
      cells. A549-CHI-R cells demonstrated cross-resistance to paclitaxel, vinorelbine
      and gemcitabine, but not to cisplatin (CDDP) or 5-fluorouracil (5-FU). These
      results indicated that HDAC1 may be associated with resistance to chidamide, and
      HDAC1 may therefore be a predictive marker for chidamide sensitivity in cancer.
      In addition, A549-CHI-R cells remained sensitive to 5-FU and CDDP, indicating a
      potential strategy for cancer therapy.

PMID- 29344125
TI  - miR-145-5p inhibits epithelial-mesenchymal transition via the JNK signaling
      pathway by targeting MAP3K1 in non-small cell lung cancer cells.
AB  - Lung cancer is one of the most common types of tumors and the leading cause of
      cancer-associated mortality in the world. Additionally, non-small cell lung
      cancer (NSCLC) accounts for ~80% of all lung cancer cases. Epithelial-mesenchymal
      transition (EMT) is an important cell biological process, which is associated
      with cancer migration, metastasis, asthma and fibrosis in the lung. In the
      present study, it was revealed that miR-145-5p was able to suppress EMT by
      inactivating the c-Jun N-terminal kinase (JNK) signaling pathway in NSCLC cells.
      Mitogen-activated protein kinase kinase kinase 1 (MAP3K1) was predicted and
      confirmed to be a novel target of miR-145-5p. Overexpression of MAP3K1 was able
      to reverse the inhibition of EMT induced by miR-145-5p via the JNK signaling
      pathway. Overall, the results revealed that miR-145-5p inhibits EMT via the JNK
      signaling pathway by targeting MAP3K1 in NSCLC cells.

PMID- 29344126
TI  - microRNA-34a overexpression inhibits cell migration and invasion via regulating
      SIRT1 in hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) remains one of the most common types of malignancy
      with high mortality and morbidity rates. Previous studies have suggested that
      microRNAs (miRs) serve pivotal functions in various types of tumor. The aim of
      the present study was to assess the association between miR-34a expression and
      HCC cell migration and invasion, and the potential underlying mechanisms. The miR
      34a overexpression vector or scramble control was transfected into human Hep3B
      and Huh7 cell lines. Transwell assays, and Matrigel and wound healing assays were
      used to detect the effects of miR-34a expression on HCC cell invasion and
      migration, respectively. The expression of miR-34a and the mRNA expression of
      other associated proteins were detected using quantitative reverse transcription
      polymerase chain reaction, and protein levels were measured using western blot
      analysis. Compared with the control, miR-34a expression was significantly
      downregulated in Hep3B and Huh7 cells, but this was reversed by the transfection
      with exogenous miR-34a (P<0.01). The number of migrated or invaded cells was
      significantly reduced by the overexpression of miR-34a in Hep3B or Huh7 cells
      (P<0.01). The expression of sirtuin 1 was upregulated, while the level of
      acetylate-p53 was downregulated by overexpression of miR-34a. Taken together, the
      results of the present study suggested that the overexpression of miR-34a may
      have suppressed HCC metastasis via inhibited cell migration and invasion.

PMID- 29344127
TI  - Mechanisms of peritoneal dissemination in gastric cancer.
AB  - Peritoneal dissemination is the most frequent metastatic pattern of gastric
      cancer, but the mechanisms underlying peritoneal dissemination are yet to be
      elucidated. Paget's 'seed and soil' hypothesis is recognized as the fundamental
      theory of metastasis. The 'seeding' theory proposes that the formation of
      peritoneal dissemination is a multistep process, including detachment from the
      primary tumour, transmigration and attachment to the distant peritoneum, invasion
      into subperitoneal tissue and proliferation with blood vascular neogenesis. In
      the present review, the progress of each step is discussed. Milky spots, as a
      lymphatic apparatus, are indicative of lymphatic orifices on the surface of the
      peritoneum. These stomata are open gates for peritoneal-free cancer cells to
      migrate into the submesothelial space. Therefore, milky spots provide suitable
      'soil' for cancer cells to implant. Other theories have also been proposed to
      clarify the peritoneal dissemination process, including the transvessel
      metastasis theory, which suggests that the peritoneal metastasis of gastric
      cancer develops via a vascular network mediated by hypoxia inducible factor
      1alpha.

PMID- 29344128
TI  - Three-dimensional cell culture: A powerful tool in tumor research and drug
      discovery.
AB  - In previous years, three-dimensional (3D) cell culture technology has become a
      focus of research in tumor cell biology, using a variety of methods and materials
      to mimic the in vivo microenvironment of cultured tumor cells ex vivo. These 3D
      tumor cells have demonstrated numerous different characteristics compared with
      traditional two-dimensional (2D) culture. 3D cell culture provides a useful
      platform for further identifying the biological characteristics of tumor cells,
      particularly in the drug sensitivity area of the key points of translational
      medicine. It promises to be a bridge between traditional 2D culture and animal
      experiments, and is of great importance for further research in the field of
      tumor biology. In the present review, previous 3D cell culture applications,
      focusing on anti-tumor drug susceptibility testing, are summarized.

PMID- 29344129
TI  - Update on radionuclide therapy in oncology.
AB  - Unstable isotopes and their capacity to emit ionizing radiation have been
      employed in clinical practice not only for diagnostic, but also for therapeutic
      purposes, with significant contribution in several fields of medicine and
      primarily in the management of oncologic patients. Their efficacy is associated
      with their ability to provide the targeted delivery of ionizing radiation for a
      determined duration. These compounds can be used for curative or palliative
      treatment, as well as for a diagnostic-therapeutic (theranostic) approach. This
      review summarises the most recent trends in radionuclide treatment for several
      malignancies, including prostate cancer, neuroendocrine tumours, and
      hematological and thyroid malignancies, in which radionuclide-based therapies
      have been employed with high effectiveness.

PMID- 29344130
TI  - Potential functions and implications of circular RNA in gastrointestinal cancer.
AB  - Circular RNAs (circRNAs) are a novel type of endogenous non-coding RNA that have
      gained attention from researchers for their involvement in multiple biological
      processes. circRNAs are ubiquitously expressed in eukaryotic cells and regulate
      gene expression at the transcriptional or post-transcriptional level by
      interacting with microRNAs (miRNAs) or other molecules. The present review
      provides an overview of circRNAs, as well as insights into their roles in the
      development and progression of gastrointestinal cancer. Furthermore, combined
      with reported data, the present review investigates the potential of circRNAs to
      become diagnostic or predictive biomarkers of gastrointestinal cancer and may
      provide novel insights into the treatment of associated cancer types.

PMID- 29344131
TI  - A novel variant translocation (1;9)(p22;q34) resulting in a DEK/NUP214 fusion
      gene in a patient with acute myeloid leukemia: A case report.
AB  - The present case report describes a 46-year-old female patient diagnosed with M4
      acute myeloid leukemia (AML), accompanied with a t(1;9)(p22;q34) chromosomal
      abnormality. Transcriptome sequencing identified a DEK proto-oncogene
      (DEK)/nucleoporin (NUP)214 fusion gene, which results from the t(6;9)(p23;q34)
      chromosomal translocation. Polymerase chain reaction analysis and fluorescence in
      situ hybridization were used to verify the existence of the DEK/NUP214 fusion
      gene. Few patients with AML with the t(6;9)(p23;q34) chromosomal translocation
      have been reported to have other chromosomal or karyotype changes. To our
      knowledge, no AML patient with the DEK/NUP214fusion gene but without the classic
      t(6;9)(p23;q34) translocations had been reported until now. The prognosis of AML
      cases with the DEK/NUP214 fusion gene is poor. The rate of complete remission is
      ~65% (71% in children, 58% in adult patients), while the estimated 5-year
      survival rate is 28% for children and 9% for adults. The 2008 revision of World
      Health Organization classification have defined the DEK/NUP214 mutation as a
      recurrent genetic abnormality of AML. The overall survival of the patient in the
      current report was ~29 months, and they relapsed twice. To the best of our
      knowledge, this is the first report of at(1;9)(p22;q34) variant translocation
      that results in expression of the DEK/NUP214 fusion gene.

PMID- 29344132
TI  - Aberrant NLRP3 inflammasome associated with aryl hydrocarbon receptor potentially
      contributes to the imbalance of T-helper cells in patients with acute myeloid
      leukemia.
AB  - Acute myeloid leukemia (AML) is a hematological malignancy in which the immune
      response serves a pivotal role in progression. Aryl hydrocarbon receptor (AHR) is
      involved in the modulation of the immune system, particularly in the
      differentiation of T-helper cell (Th) subsets. Although the NLR family pyrin
      domain-containing 3 (NLRP3) inflammasome has been implicated as essential in the
      pathogenesis of autoimmune and inflammatory diseases, the role it serves in the
      development of AML remains unknown. Therefore, in order to identify and describe
      the possible roles of AHR, as well as NLRP3 inflammasome, in the pathogenesis of
      AML and their relationship with Th subsets (Th1 Th22), the present study
      investigated the mRNA expression levels of AHR and NLRP3 inflammasome molecules
      in the peripheral blood and bone marrow. Concentrations of plasma IL-18 were also
      investigated in peripheral blood by ELISA, as well as the proportions of Th22 and
      Th1. In the present study, there were three groups: Newly diagnosed (ND)
      patients; complete remission (CR); and normal controls. A markedly increased
      expression of NLRP3 inflammasome molecules in bone marrow mononuclear cells
      (BMMCs) from newly diagnosed (ND) patients compared with patients in complete
      remission (CR) was identified. NLRP3 inflammasome molecules were also observed to
      be aberrantly expressed in peripheral blood (PB) mononuclear cells (PBMCs),
      accompanied with aberrant interleukin (IL)-18 levels in PB plasma. The relative
      level of IL-18 mRNA became normal after the ND patients with AML achieved CR. In
      bone marrow, the expression of AHR was significantly higher in ND patients than
      in CR patients. Furthermore, the expression level of NLRP3 inflammasome molecules
      was significantly correlated with AHR expression in patients with AML. In the Th
      subsets, a significantly increased proportion of Th22 in PB from ND patients
      compared with CR patients or controls was identified, accompanied with decreased
      Th1. It was concluded that the NLRP3 inflammasome, associated with AHR, was
      involved in the development of AML and may have influenced the differentiation of
      Th subsets.

PMID- 29344133
TI  - Improved treatment of early small hepatocellular carcinoma using sorafenib in
      combination with radiofrequency ablation.
AB  - Small hepatocellular carcinoma is an important leading cause of death amongst
      cancer patients, our study was designed in order to test the hypothesis that
      radiofrequency ablation (RFA) combined with a chemotherapeutic drug would improve
      the outcome for patients. Two groups of patients presenting early small
      hepatocellular carcinoma were treated with either conventional RFA alone (50
      individuals in the control group), or with a combination of RFA and oral
      sorafenib (40 individuals in an observation group). Individual clinical and
      laboratory evaluations were done during an average follow-up time of 35 months,
      and all the data recorded was used to compare results of both treatment
      approaches. Tumor-free survival, relapse rate and survival rate, RFA interval and
      number of treatments, overall efficacy and the incidence of complications were
      analyzed. Serum levels of vascular endothelial growth factor (VEGF), connective
      tissue growth factor (CTGF), hypoxia inducible factor-1alpha (HIF-1alpha) and
      osteopontin (OPN) were measured and compared. Our results show that the patients
      in the treatment group had statistically significant prolonged tumor-free
      survival, decreased relapse and increased survival rates. Also, the patients in
      the treatment group had significantly more prolonged average intervals of RFA and
      a lower number of treatments. Furthermore, the overall efficacy in the treatment
      group was increased, yet the incidence of complications was similar between both
      groups. Moreover, the serum levels of known tumorigenic factors VEGF, CTGF, HIF
      1alpha and OPN, which were similar between both groups before treatment, improved
      more markedly after the treatment in the observation group patients. Based on
      these findings, we propose that sorafenib in combination with percutaneous RFA is
      safe and efficacious, and a superior treatment for early small hepatocellular
      carcinoma. Larger studies are needed to corroborate our results.

PMID- 29344134
TI  - A novel classification system for the evaluation and reconstruction of oral
      defects following oncological surgery.
AB  - Accurate evaluation of oral tissue defects following oncological surgery is
      necessary for the subsequent reconstruction. However, there is currently no
      effective classification system for oral defects in the clinical setting. The
      present study therefore developed a clinical classification system for the
      evaluation and reconstruction of oral defects. A retrospective cohort study was
      performed. A two-dimensional classification system based on coronal computed
      tomography/magnetic resonance imaging was developed and validated by 145 cases
      with oral defects. Oral defects could be classified into 6 types (I-VI)
      horizontally and 2 classes (a and b) vertically. The proportion of the various
      types was as follows: Type I, 35.9%; type II, 21.4%; type III, 23.4%; type IV,
      4.8%; type V, 2.1%; and type VI, 12.4%. Among them, 91 cases (62.8%) were class a
      and 54 cases (37.2%) were class b. Type Ia-Va represented the unilateral 1-5
      subsites involving superficial oral defects without mandibular continuity
      destruction (88 cases, 60.7%). Type Ib-Vb (+M) represented the unilateral 1-5
      subsites involving deep oral defects with segmental mandibular continuity
      destruction (38 cases, 26.2%). Type I-V (+S) represented the unilateral through
      and through oral defects with cheek skin involvement (10 cases, 6.9%). Type VI
      represented bilateral oral defects (18 cases, 12.4%). The present classification
      system for the evaluation of the oral defects was simple and practical, and could
      identify the common types of oral defects and guide the reconstruction.

PMID- 29344135
TI  - Identification of differentially expressed genes in oral squamous cell carcinoma
      TCA8113 cells.
AB  - Previous studies have demonstrated that cancer cells with increased levels of
      aldehyde dehydrogenase 'bright' activity (ALDHbr) exhibit stem cell properties
      compared with cells exhibiting decreased ALDH activity (ALDHlow). To screen
      possible biomarkers of cancer stem cells in tongue squamous cell carcinoma,
      ALDHbr and ALDHlow cells were isolated from the tongue squamous cell carcinoma
      TCA8113 cell line, and suppression subtractive hybridization was performed to
      identify differentially expressed genes in the two subpopulations. A total of 240
      positive clones were randomly selected for sequencing and were functionally
      characterized using bioinformatical tools. The results of the present study
      identified the differential expression of 104 clones, 62 of which corresponded to
      known genes and 42 of which corresponded to unknown genes. Cluster analysis
      revealed that the known genes were involved in the regulation of the cell cycle
      and cell differentiation. In addition, analysis of 10 signaling pathways revealed
      that genes were markedly altered in the ALDHbr cell subpopulation. Additional
      study is required to identify the function that these genes serve in the
      biomolecular regulatory mechanisms of cancer stem cells and to assist in
      explaining the biological behavior of oral squamous cell carcinoma.

PMID- 29344136
TI  - Clinical outcome of extended-field irradiation vs. pelvic irradiation using
      intensity-modulated radiotherapy for cervical cancer.
AB  - The aim of the present study was to evaluate the distinctions in survival and
      toxicity between patients with cervical cancer with common iliac node or para
      aortic node involvement, who were treated with extended-field intensity-modulated
      radiotherapy (EF-IMRT) and patients with or without lower involved pelvic nodes,
      who were treated with pelvic IMRT. A total of 55 patients treated with EF-IMRT
      and 52 patients treated with pelvic IMRT at the Sun Yat-Sen University Cancer
      Center (Guangzhou, China) were retrospectively analyzed. Patients treated with EF
      IMRT had the highest level of lymph node involvement to the para-aortic or common
      iliac nodes, while patients treated with pelvic IMRT had no para-aortic or common
      iliac nodes involved (P<0.001). The median follow-up time was 29.5 months. The 3
      year overall survival (OS) rates of EF-IMRT and pelvic IMRT were 79.4 and 82.3%
      (P=0.45), respectively, and the 3-year disease-free survival (DFS) rates of EF
      IMRT and pelvic IMRT were 61.0 and 73.7% (P=0.55), respectively. Cox's regression
      analysis revealed that EF irradiation was a protective prognostic factor for OS
      and DFS. A total of 16 patients in the EF-IMRT group and 13 patients in the
      pelvic IMRT group experienced treatment failure (P=0.67), with the patterns of
      failure being the same for the two groups (P=0.88). The cumulative incidence of
      grade 3 and 4 acute toxicities in the EF-IMRT group was 34.5%, in comparison with
      19.2% in the pelvic group (P=0.048). The results of the present study suggest
      that patients with cervical cancer with grossly involved common iliac or para
      aortic nodes should be electively subjected to EF irradiation to improve the
      survival and alter patterns of recurrence. Notably, EF irradiation delivered via
      IMRT exhibits an increased toxicity incidence, however, this remains within an
      acceptable range.

PMID- 29344137
TI  - The association between aquaporin-1 expression, microvessel density and the
      clinicopathological features of hepatocellular carcinoma.
AB  - The present study aimed to evaluate the effects of aquaporin-1 (AQP1) level and
      intratumoral microvessel density (IMD) on the clinicopathological features of
      patients with hepatocellular carcinoma (HCC). The AQP1 expression levels, IMD and
      AQP1/IMD ratios in patients with HCC were measured using a semi-quantitative
      immunohistochemical technique. The association between these features and
      clinicopathological variables were evaluated. The prognostic impact of AQP1 and
      IMD on overall survival (OS), and 5-year disease-free survival (DFS) of HCC
      patients was investigated retrospectively. P<0.05 was considered to indicate a
      statistically significant difference. A total of 90 cases of HCC were included in
      the present study. AQP1 was markedly expressed in the membranes of microvessels
      and small vessels, but seldom in hepatocellular carcinoma cells. Blood vessels in
      the tumors were markedly stained by anti-cluster of differentiation 34 antibody.
      AQP1 expression and IMD was significantly correlated with tumor size, histologic
      grade, Child-Pugh classification, microvascular invasion and tumor-node
      metastasis (TNM) stage (P<0.05). Concurrently, for the 5-year DFS and OS, a
      larger tumor size, poorly differentiated histological grade, B and C Child-Pugh
      classification, presence of microvascular invasion, high TNM stage, a high AQP1
      expression and a high IMD were significant risk factors for mortality.
      Multivariate analysis revealed that TNM stage and IMD were independent
      unfavorable prognostic markers for 5-year DFS (P=0.049 and P=0.025, respectively)
      and OS (P=0.043 and P=0.042, respectively). These data suggest that high AQP1
      expression and IMD are associated with tumor progression and prognosis in HCC.
      The IMD level may serve as an independent indicator for the 5-year DFS and OS.

PMID- 29344138
TI  - Clinical and genetic analysis of tuberous sclerosis complex-associated renal
      angiomyolipoma in Chinese pedigrees.
AB  - Tuberous sclerosis complex-associated renal angiomyolipoma (TSC-RAML) confers a
      high risk of bleeding and even mortality. However, data on TSC-RAML in Chinese
      pedigrees is extremely lacking. The present study aimed to investigate its
      clinical and genetic characteristics by obtaining a detailed medical history from
      6 probands and their family members, and reassessing blood tests, computed
      tomography and renal dynamic imaging examinations that were conducted in the TSC
      RAML patients. The TSC1/TSC2 mutation was detected in 2 families. A total of 3
      TSC-RAML patients underwent partial nephrectomy due to a high bleeding risk, and
      the other 2 were treated with everolimus. The remaining 6 TSC-RAML patients
      received no clinical intervention and only had clinical follow-uzp. It was found
      that nearly 37% (18/49) were TSC patients, with the mean +/- standard deviation
      diagnostic age being 34.22+/-17.73 years old in the 6 pedigrees, 61% (11/18) of
      whom suffered from TSC-RAML. In the 11 TSC-RAML patients, the maximum diameter of
      the tumor ranged between 1.20 and 32.50 cm (mean +/- standard deviation, 11.48+/
      8.40 cm), the unilateral glomerular filtration rate ranged between 27.20 and
      60.10 ml/min (mean +/- standard deviation, 42.55+/-9.73 ml/min), the serum
      creatinine level ranged between 40.00 and 90.00 umol/l (mean +/- standard
      deviation, 64.84+/-16.15 umol/l) and the hemoglobin concentration ranged between
      76.00 and 140.00 g/l (mean +/- standard deviation, 107.73+/-21.04 g/l).
      Pathogenic mutations of TSC1 (c.733C>T) and TSC2 (c.788_789insC) were detected in
      family B and C, respectively, as well as certain non-pathogenic mutations, with
      the maximum diameter of TSC-RAML being 0 cm and 10.3 cm in the two patients from
      family B and 16 cm and 1.2 cm in the two patients from family C. Expression of
      phosphorylated-mechanistic target of rapamycin was determined in the TSC-RAML
      tissues by immunohistochemistry. The maximum diameter of the tumor decreased by
      4.90 and 5.30 cm, respectively, in the 2 patients treated with everolimus after 3
      months. In conclusion, TSC cannot be easily diagnosed due to its variable
      characteristics. Growth of TSC-RAML may increase the bleeding risk and reduce the
      level of hemoglobin, but it does not greatly affect renal function. Individual
      differences in tumor dimensions existed even with the same pathogenic mutation,
      except for cases of coexistent non-pathogenic mutations. Everolimus treatment
      appears to be able to significantly reduce the size of TSC-RAML.

PMID- 29344139
TI  - NLS-RARalpha is a novel transcriptional factor.
AB  - Acute promyelocytic leukemia (APL) is characterized by the presence of the
      promyelocytic leukemia (PML)-retinoic acid receptor-alpha (RAR-alpha) fusion
      protein. PML-RARalpha can be cleaved by neutrophil elastase (NE) in several
      positions in cells in the promyelocytic stage, nuclear location signal (NLS)
      negative PML and NLS-RARalpha may be the products of PML-RARalpha by NE. The
      function of NLS-RARalpha may be affected by the addition of NLS, which would
      alter its localization in cells, as the role of NLS is to identify proteins for
      transport to the nucleus. Preliminary experiments demonstrated that the
      overexpression of NLS-RARalpha in HL-60 cells could promote cellular
      proliferation and inhibit cellular differentiation. Following treatment with all
      trans retinoic acid (ATRA), the degree of cellular differentiation was enhanced.
      In the present study, the localization of NLS-RARalpha was identified and its
      activity as a novel transcriptional factor was assessed, which may be critical in
      the development of APL. The location of NLS-RARalpha was detected in the nucleus
      and cytoplasm by indirect immunofluorescence and western blot analysis, with
      expression in the nucleus revealed to be increased compared with that in the
      cytoplasm. Next, native-PAGE was performed and NLS-RARalpha and RXRalpha were
      revealed to form heterodimers in the nucleus. In addition, co-immunoprecipitation
      revealed an interaction between NLS-RARalpha and retinoid X receptor-alpha
      (RXRalpha). An electrophoresis mobility shift assay (EMSA) indicated that NLS
      RARalpha could bind retinoic acid response elements (RAREs) in the presence of
      ATRA. Indeed, NLS-RARalpha could bind RAREs just as WTRARalpha could, including
      the RAREs direct repeat-2 (DR-2) and DR-5. In addition, results from a luciferase
      reporter gene assay demonstrated that NLS-RARalpha could mediate the activity of
      RAREs that it bound. Together, these results indicated that NLS-RARalpha may be a
      novel transcription factor that contributes to leukemogenesis by competitively
      binding RAREs as heterodimers with RXRalpha, just as PML-RARalpha does, thus
      repressing the gene transcription essential for myeloid differentiation. These
      findings indicate the potential role of NLS-RARalpha targeted therapy in APL.

PMID- 29344140
TI  - Familial genetic tuberous sclerosis complex associated with bilateral giant renal
      angiomyolipoma: A case report.
AB  - Tuberous sclerosis complex (TSC) is an autosomal dominant disease involving
      multiple organs, but there are a limited number of reports on family TSC. In the
      present report, a case of a 52-year-old female with a familial genetic TSC,
      associated with bilateral giant renal angiomyolipoma, was described. The mother,
      second elder brother and daughter of the patient all exhibited TSC, but the
      clinical manifestations, and therapeutic prognosis between the family members
      were not the same. The present case report aimed at identifying an effective
      diagnostic method and treatment through additional study of familial genetic TSC,
      in order to prolong and improve the quality of life for patients with TSC.
      According to the present case and relevant literature reviews, it is suggested
      that fetal gene detection during pregnancy could prevent the passing of this
      disease onto further generations. Furthermore, early application of drug
      treatment may control the development of the disease in diagnosed patients. The
      combination of classical treatments with a small dose of mammalian target of
      rapamycin inhibitors is the typical recommendation, which may control the
      development of the disease more effectively and decrease adverse side-effects.

PMID- 29344141
TI  - The expression of S100B protein in serum of patients with brain metastases from
      small-cell lung cancer and its clinical significance.
AB  - The objective of the present study was to investigate the expression of S100B
      protein in serum of patients with brain metastases from small cell lung cancer
      (SCLC), and its clinical significance. A total of 138 patients with SCLC were
      selected from June 2013 to December 2015. Simultaneously, 138 healthy adult
      volunteers (healthy controls) were selected in the medical examination center of
      People's Hospital of Rizhao. Among the 138 patients with SCLC, 48 had liver
      metastases and 44 had brain metastases. Of the remaining 46 patients, 20 were
      initially diagnosed with SCLC and 26 underwent surgery and postoperative
      chemotherapy. The levels of serum S100B in patients and healthy controls were
      measured by ELISA, and analyzed by SPSS 20.0 statistical software. The serum
      S100B protein levels in patients with SCLC were significantly higher than those
      in healthy controls (p<0.05). Among the subgroups of patients with SCLC, the
      levels of serum S100B in patients with brain metastases were significantly higher
      than in the other subgroups (p<0.05). No significant differences were found
      between the other subgroups, except for the brain metastases group. We found that
      serum S100B protein expression levels were significantly reduced in patients with
      brain metastases after cobalt-60 radiotherapy (p<0.05). During follow-up, we
      found that higher expression of S100B protein was usually associated with poorer
      prognosis, higher mortality rate at 1 year, and lower survival rate. In
      conclusion, S100B protein can serve as a serological marker for brain metastases
      from SCLC, which provides important theoretical support for early detection of
      brain metastases.

PMID- 29344142
TI  - Isolation and identification of tumor-initiating cell properties in human
      gallbladder cancer cell lines using the marker cluster of differentiation 133.
AB  - The present study aimed to isolate and identify the properties of the cluster of
      differentiation (CD)133+ subset in human gallbladder cancer cells. The CD133+ and
      CD133- subpopulations of the GBC-SD cell line were separated using immunomagnetic
      separation, and the biological features of the two subpopulations were analyzed
      in vitro and in vivo. In particular, the present study aimed to determine whether
      the two subpopulations were resistant to anti-tumor reagents and to identify the
      underlying molecular mechanisms involved. Following cell sorting of GBC-SD cells
      using immunomagnetic beads, 90.2+/-2% of cells were identified as CD133+.
      Immunofluorescence confirmed that CD133 was expressed at higher levels in the
      Cd133+ group compared with the CD133- group. The proliferation of the CD133+
      group was significantly increased compared with the CD133- group in vitro and in
      vivo. Following treatment with fluorouracil or gemcitabine, cells in the CD133+
      group exhibited a decreased sensitivity to these drugs. The number of
      transmembrane cells was significantly increased in the CD133+ group compared with
      the CD133- group. In addition, the expression levels of ATP binding cassette
      subfamily G member 2, CD44, C-X-C motif chemokine receptor 4 (CXCR4),
      phosphorylated-protein kinase B (Akt) and CD133 in the CD133+ group were
      significantly increased, compared with those in the CD133- group. In CD133+ GBC
      SD cells, stromal cell-derived factor 1alpha (SDF-1alpha) or treatment with
      AMD3100, an inhibitor of CXCR4, promotes or suppresses the SDF-1alpha/CXCR4 axis,
      respectively, resulting in increased or decreased CD133 expression through the
      Akt signaling pathway. Inhibition of the Akt signaling pathway resulted in
      decreased CD133 expression in GBC-SD cells. Immunomagnetic beads were
      successfully used for isolation of the CD133+ subset from GBC-SD cells.
      Furthermore, the CD133+ subset revealed an increased potential for tumor
      formation, cell proliferation, invasion and resistance to chemotherapeutic agents
      with expression of stem cell-associated genes. Therefore, in GBC-SD cells, the
      CXCR4/Akt/CD133 signaling pathways may be activated.

PMID- 29344143
TI  - Function of cell-cycle regulators in predicting silent pituitary adenoma
      progression following surgical resection.
AB  - The present study investigated the use of cell-cycle regulators for predicting
      the progression of silent pituitary adenoma (SPA) following surgical resection,
      via immunohistochemical analysis of tumor samples obtained by surgical resection.
      The medical records of patients diagnosed with SPA between January 2000 and
      December 2013 in the Samsung Changwon Hospital, Sungkyunkwan University School of
      Medicine (Changwon, South Korea) were reviewed. Immunohistochemical staining was
      performed on sections of the archived, paraffin-embedded tissues obtained by
      surgery, with all tissues stained for cell-cycle regulatory proteins p16, p15,
      p21, cyclin-dependent kinase (CDK)4, CDK6, retinoblastoma protein (pRb) and
      cyclin D1, as well as E3 ubiquitin-protein ligase mib1 (MIB-1) antigen and p53.
      The primary end-point was to investigate the expression of cell-cycle regulatory
      proteins in SPA. The secondary end-point was to estimate the progression-free
      survival of patients with SPA following surgical resection and to identify its
      association with the expression of cell-cycle regulatory proteins. Of the 127 SPA
      samples, 44 (34.6%) were from patients with progression during a mean follow-up
      period of 62.4 months (range, 24.2-118.9 months). Immunohistochemical
      overexpression was identified in 61 samples (48.0%) for p16, 38 samples (29.9%)
      for p15, 19 samples (15.0%) for p21, 49 samples (38.6%) for CDK4, 17 samples
      (13.4%) for CDK6, 57 samples (44.9%) for pRb and in 65 samples (51.2%) for cyclin
      D1. Multivariate analysis revealed that null cell adenoma [95% confidence
      interval (CI), 0.276-0.808], somatotroph SPAs (95% CI, 1.296-3.121), corticotroph
      SPAs (95% CI, 1.811-4.078), pluripotent SPAs (95% CI, 2.264-5.194), decreased
      expression of p16 (95% CI, 2.724-5.588), overexpression of pRb (95% CI, 2.557
      5.333), cyclin D1 (95% CI, 1.894-4.122) and MIB-1 (95% CI, 1.561-4.133),
      increased mitotic index (95% CI, 1.228-4.079), increased p53 expression (95% CI,
      1.307-4.065) and invasion into the cavernous sinus (95% CI, 3.842-7.502)
      predicted SPA progression following resection. The results of the present study
      suggested that specific cell-cycle regulators, including p16, cyclin D1 and pRb,
      were associated with SPA progression.

PMID- 29344144
TI  - Melanoma differentiation-associated gene-7 suppresses human gastric cancer cell
      invasion and migration.
AB  - Gastric cancer is one of the most common types of cancer in the world. Patients
      with gastric cancer often respond poorly to conventional chemotherapies,
      therefore more comprehensive therapy is required. Melanoma differentiation
      associated gene-7 (MDA-7), also termed interleukin-24, is a potent tumor
      suppressor gene. Numerous studies have demonstrated that MDA-7 suppresses the
      growth and induces the apoptosis of cancer cells. In the present study, the MDA-7
      gene was transfected into human gastric cancer AGS cells using adenovirus.
      Transwell and wound healing assays were performed to evaluate AGS cell invasion
      and migration, respectively. Western blotting was used to detect the expression
      of epithelial (E)-cadherin, cluster of differentiation (CD)44 and matrix
      metalloproteinase (MMP)-2 and MMP-9 proteins. A recombinant virus package was
      successfully constructed, and it was verified using western blotting that
      exogenous MDA-7 was highly expressed in the AGS cells. MDA-7 overexpression
      inhibited invasion and migration, decreased CD44, MMP-2 and MMP-9 expression, and
      increased epithelial (E-)cadherin expression in the AGS cells. Results of the
      present study revealed that MDA-7 inhibits gastric cancer invasion and metastasis
      by inhibiting CD44, MMP-2 and MMP-9 expression and by promoting E-cadherin
      expression.

PMID- 29344145
TI  - MicroRNA-320 inhibits cell proliferation and invasion in breast cancer cells by
      targeting SOX4.
AB  - Dysregulation of microRNAs (miRs) can contribute to cancer development and
      progression. In the present study, the function and underlying molecular
      mechanisms of miR-320 in breast cancer tumorigenesis and progression were
      investigated. The results of a reverse transcription-quantitative polymerase
      chain reaction analysis demonstrated that miR-320 was frequently downregulated in
      breast cancer tissues compared with adjacent normal tissues. In addition,
      knockdown of miR-320 in breast cancer cell lines promoted cell proliferation and
      invasion in vitro, whereas miR-320 overexpression had the opposite effect.
      Furthermore, a Dual-Luciferase reporter assay indicated that SRY-box 4 (SOX4) is
      a direct target of miR-320, and the restoration of SOX4 in miR-320-overexpressing
      cells attenuated the tumor-suppressive effects of miR-320. Collectively, these
      results indicated that miR-320 acts as a tumor suppressor in breast cancer
      tumorigenesis and progression.

PMID- 29344146
TI  - Integrated microRNA-mRNA analyses of distinct expression profiles in follicular
      thyroid tumors.
AB  - MicroRNAs (miRNAs/miRs) are small non-coding RNAs identified in plants, animals
      and certain viruses; they function in RNA silencing and post-transcriptional
      regulation of gene expression. miRNAs also serve an important role in the
      pathogenesis, diagnosis and treatment of tumors. However, few studies have
      investigated the role of miRNAs in thyroid tumors. In the present study, the
      expression of miRNA and mRNA was compared between follicular thyroid carcinoma
      (FTC) and follicular thyroid adenoma (FA) samples, and then miRNA-mRNA regulatory
      network analysis was performed. Microarray datasets (GSE29315 and GSE62054) were
      downloaded from the Gene Expression Omnibus, and profiling data were processed
      with R software. Differentially expressed miRNAs (DEMs) and differentially
      expressed genes (DEGs) were determined, and Gene Ontology enrichment analysis was
      subsequently performed for DEGs using the Database for Annotation, Visualization
      and Integrated Discovery. The target genes of the DEMs were identified with
      miRWalk, miRecords and TarMir databases. Network analysis of the DEMs and DEMs
      targeted DEGs was performed using Cytoscape software. In GSE62054, 23
      downregulated and 9 upregulated miRNAs were identified. In GSE29315, 42
      downregulated and 44 upregulated mRNAs were identified. A total of 36 miRNA-gene
      pairs were also identified. Network analysis indicated a co-regulatory
      association between miR-296-5p, miR-10a, miR-139-5p, miR-452, miR-493, miR-7, miR
      137, miR-144, miR-145 and corresponding targeted mRNAs, including TNF receptor
      superfamily member 11b, benzodiazepine receptor (peripheral) -associated protein
      1, and transforming growth factor beta receptor 2. These results suggest that
      miRNA-mRNAs networks serve an important role in the pathogenesis, diagnosis and
      treatment of FTC and FA.

PMID- 29344147
TI  - Systematic analysis of the molecular mechanism of microRNA-124 in hepatoblastoma
      cells.
AB  - The present study aimed to identify the molecular mechanisms of microRNA-124
      (miRNA-124/miR-124) in hepatoblastoma. The GSE6207 microarray dataset, obtained
      from the Gene Expression Omnibus database, included samples extracted from HepG2
      cells transfected with miR-124 duplex (the experimental group) or negative
      control (the control group) at 4, 8, 16, 24, 32, 72 and 120 h after transfection.
      Differentially expressed genes (DEGs) were screened between the two groups. miR
      124 activity was inferred based on the expression of its target genes. The mRNAs
      targeted by miR-124 were predicted and a miR-124-target mRNA network was
      constructed. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes
      pathway enrichment analyses were performed for the target genes. The number of
      DEGs was highest at 72 h. The experimental group had higher miR-124 activity than
      that of the control group at 4, 8, 16, 24 and 120 h. Small GTPase-mediated signal
      transduction and Ras protein signal transduction were significant GO terms
      enriched with syndecan binding protein (SDCBP), Ras homolog family member G
      (RHOG) and Rho-GDP dissociation inhibitor-alpha (ARHGDIA). Regulation of actin
      cytoskeleton, D-glutamine and D-glutamate metabolism, and axon guidance were
      significant pathways. Axon guidance pathway was associated with neuropilin
      (NRP1), MET proto-oncogene, receptor tyrosine kinase (MET) and semaphorin 7A, GPI
      membrane anchor (SEMA7A). Small GTPase-mediated signal transduction, Ras protein
      signal transduction, regulation of actin cytoskeleton pathway, D-glutamine and D
      glutamate metabolism pathway, axon guidance pathway, SDCBP, RHOG, ARHGDIA, NRP1,
      SEMA7A, and MET may be implicated in the underlying mechanisms of miR-124
      overexpression in hepatoblastoma.

PMID- 29344148
TI  - Identification of potentially critical differentially methylated genes in
      nasopharyngeal carcinoma: A comprehensive analysis of methylation profiling and
      gene expression profiling.
AB  - The present study aimed to identify potentially critical differentially
      methylated genes associated with the progression of nasopharyngeal carcinoma
      (NPC). Methylation profiling data of GSE62336 deposited in the Gene Expression
      Omnibus database were used to identify differentially methylated regions (DMRs)
      and differentially methylated CpG islands (DMIs). Concurrently, differentially
      expressed genes (DEGs) were identified using a meta-analysis of three gene
      expression datasets (GSE53819, GSE13597 and GSE12452). Subsequently, methylated
      DEGs were identified by comparing DMRs and DEGs. Furthermore, functional
      associations of these methylated DEGs were analyzed via constructing a functional
      network using GeneMANIA prediction server. In total, 1,676 hypermethylated genes,
      28 hypomethylated genes, 17 DMIs and 2,983 DEGs (1,655 upregulated and 1,328
      downregulated) were identified. Among these DEGs, 135 downregulated genes were
      hypermethylated; of these, dual specificity phosphatase 6 (DUSP6) and tenascin XB
      (TNXB) contained DMIs. In the functional network, 154 genes and 1,651 association
      pairs were included. DUSP6 was predicted to exhibit genetic interactions with
      other hypermethylated DEGs such as malic enzyme 3 and ST3 beta-galactoside alpha
      2,3-sialyltransferase 5; TNXB was predicted to be co-expressed with a set of
      hypermethylated DEGs, including EPH receptor B6, aldehyde dehydrogenase 1 family,
      member L1 and glutathione peroxidase 3. The hypermethylated DEGs may be involved
      in the progression of NPC, and they may become novel therapeutic targets for NPC.

PMID- 29344149
TI  - Hepatoma-derived growth factor functions as an unfavorable prognostic marker of
      human gliomas.
AB  - Hepatoma-derived growth factor (HDGF) regulates various cellular processes
      involved in the onset and development of tumors. To evaluate the role of HDGF in
      human gliomas, western blotting analysis, immunohistochemistry staining and
      reverse transcription-quantitative polymerase chain reaction were performed to
      detect HDGF protein and mRNA expression levels in glioma and intractable
      epileptic brain tissue. Various clinicopathological characteristics, including
      age, gender, World health Organization grade, HDGF expression level, Karnofsky
      performance Status (KPS) and Ki-67 index were obtained from medical records. The
      correlation between HDGF expression and these clinicopathological characteristics
      was statistically evaluated. Following this, multivariate liner regression was
      used to evaluate their effect on patient survival time. HDGF expression, at the
      protein and mRNA levels, was observed to be more upregulated in glioma tissues
      compared with intractable epileptic brain tissue without tumor. Furthermore, the
      level of HDGF expression was positively associated with the grade of malignancy
      [grades II~IV, Ki-67 index >=20% or KPS <80 (P<0.05)] and poor prognosis in
      glioma patients. Notably, the univariate survival analysis identified a negative
      correlation between HDGF-expression and survival time (P<0.01) and multivariate
      liner regression demonstrated that HDGF expression is an independent prognostic
      factor for gliomas (P=0.01). Overall, HDGF upregulation may be a crucial step in
      the development and invasion of glioma. Further survival analysis highlighted its
      prognostic value for this malignancy, implying its potential as a promising
      therapeutic target for gliomas.

PMID- 29344150
TI  - Expression of CD24 and B7-H3 in breast cancer and the clinical significance.
AB  - This study aimed to investigate the correlation between the expression of CD24
      and B7-H3 in breast cancer tissues and the clinical significance. Expression of
      CD24 and B7-H3 in breast cancer and adjacent tissues were detected by
      immunohistochemistry. Quantitative PCR was used to detect the expression of CD24
      and B7-H3 mRNA in breast cancer and adjacent tissues. The expression of CD24 and
      B7-H3 protein in breast cancer and adjacent tissues was detected by
      immunoblotting. The correlation between the expression levels of the two proteins
      was analyzed and the relationship between the expression of two proteins and the
      5-year survival of breast cancer patients was investigated. CD24 and B7-H3 were
      positively expressed in breast cancer and adjacent tissues, the CD24-positive
      rate was 75.7 and 25.7%, respectively, and the B7-H3-positive rate was 56.8 and
      43.2%, respectively, and the differences were statistically significant (P<0.05).
      The expression of CD24 was positively correlated with the expression of B7-H3
      (Spearman's correlation coefficient r, 0.297; p=0.036). The positive and negative
      expression of CD24 and B7-H3 significantly affected the 5-year survival of breast
      cancer patients (P<0.05). Quantitative PCR results showed that the expression
      levels of CD24 and B7-H3 mRNA in breast cancer tissues were significantly higher
      than those in adjacent tissues (P<0.05). The expression levels of CD24 and B7-H3
      protein in breast cancer tissues were also significantly higher than those in
      adjacent tissues (P<0.05). CD24 and B7-H3 were highly expressed in breast cancer,
      suggesting that both CD24 and B7-H3 were related to the development of breast
      cancer. Five-year survival analysis of breast cancer patients showed that the
      high expression of CD24 and B7-H3 were correlated with the poor prognosis of
      patients. Thus, CD24 and B7-H3 may become new targets for the treatment of breast
      cancer.

PMID- 29344151
TI  - Expression of EZH2 in endometrial carcinoma and its effects on proliferation and
      invasion of endometrial carcinoma cells.
AB  - Expression of enhancer of zeste homolog 2 (EZH2) has been implicated in cancer
      pathology, but research on its mechanistic activity is limited. The present study
      sought to assess the levels expression of EZH2 in patients with endometrial
      carcinoma (EC) and to explore the effects of EZH2 downregulation on the
      biological behavior of endometrial carcinoma RL-952 cells. Samples were obtained
      from a total of 104 patients with EC and an immunohistochemical assay was used to
      detect the expression of EZH2 in cancer and adjacent tissues. The relationship
      between the expression of EZH2 and the clinicopathological features was analyzed.
      Endometrial carcinoma RL-952 cells were transfected with chemically synthesized
      siRNA to conduct targeting inhibition of EZH2 expression. The expression levels
      of EZH2 protein were detected by immunoblotting. MTT and Transwell assays were
      used to detect the changes of cell proliferation and invasion after EZH2
      downregulation. Of the 104 cases of endometrial carcinoma samples, 71 cases
      showed positive expression of EZH2, with an expression rate of 68.27%. In 104
      cases of adjacent tissue samples, 25 cases showed positive expression of EZH2,
      with an expression rate of 24.03%. The expression of EZH2 in endometrial
      carcinoma tissue was significantly higher than that in adjacent tissue (P<0.05).
      The expression of EZH2 in endometrial carcinoma tissue was not correlated with
      the menopausal status and age of patients (P>0.05), but was correlated with the
      histological grade, depth of tumor invasion, lymph node metastasis and TNM stage
      (P<0.05). The expression of E2H2 was significantly downregulated by si-E2H2 and
      the proliferation and invasion abilities of cells were significantly reduced
      after EZH2 downregulation (P<0.05). EZH2 is closely related to the development of
      endometrial carcinoma and can enhance the proliferative activity of endometrial
      carcinoma RL-952 cells and promote cell invasion.

PMID- 29344152
TI  - Regulation of autophagy inhibition and inflammatory response in glioma by Wnt
      signaling pathway.
AB  - The objective of this study was to investigate the mechanism of the function of
      Wnt signaling pathway in regulating autophagy and inflammatory response in glioma
      cells. Human brain glioma cells U118 were selected and divided into three groups:
      i) the Wnt signaling inhibitor IWR-1 group (the observation group); ii) the PBS
      negative control group (the PBS group) and iii) the blank control group. After 24
      h culture, Wnt5a/beta-catenin protein, autophagy marker, microtubule-associated
      proteins-1A1B-light-chain-3C (LC-3) II and Beclin I, and inflammatory factors IL
      6 and TNF-alpha protein expression levels were evaluated using western blotting.
      Compared with both control groups, Wnt5a/beta-catenin, IL-6 and TNF-alpha protein
      expression levels were significantly lower, and LC-3II and Beclin I protein
      expression levels were significantly higher in the observation group. In
      conclusion, Wnt5a/beta-catenin signaling pathway regulates autophagy and
      inflammatory response of glioma cells.

PMID- 29344153
TI  - Efficacy and prognosis of surgery combined with 125I seed implantation in
      treatment of recurrent glioma.
AB  - This study evaluated the efficacy of surgery combined with 125I seed implantation
      in the treatment of recurrent glioma, and analyzed prognosis-influencing factors.
      A total of 66 patients with recurrent gliomas in Yidu Central Hospital of Weifang
      were enrolled in the study from April, 2011 to March, 2014. Patients were
      randomly divided into a control and an observation group, with 33 patients in
      each group. Patients in the control group were treated with surgery alone, and
      those in the observation group received surgery combined with 125I seed
      implantation. Short-term curative effects in the two groups were compared using
      evaluation criteria for solid tumors. The comparison included the postoperative
      adverse reactions, the life quality (using the Karnofsky Performance Status or
      KPS), the survival time and prognostic factors (using the Kaplan-Meier survival,
      log-rank test and Cox regression analyses). Our results showed the objective
      response and disease control rates in the observation group were significantly
      higher than those in the control group (P<0.05). While no significant differences
      in postoperative adverse reactions were found between the two groups (P>0.05).
      The KPS score in the observation group was significantly higher than that in the
      control group at different time points after surgery (P<0.05). The survival rate
      and overall survival time of those in the observation group were significantly
      higher than those of the patients in the control group (P<0.05). The univariate
      analysis showed that preoperative KPS score, tumor pathological grade and degree
      of tumor resection were adverse factors influencing the prognosis of the patients
      (P<0.05). Also, multivariate Cox regression showed that preoperative KPS score,
      tumor pathological grade, and degree of tumor resection were independent risk
      factors of prognosis. Based on our findings, surgery combined with 125I seed
      implantation can improve the survival rate of patients with recurrent glioma and
      prolong their survival time. Tumor pathological grade, degree of tumor resection
      and KPS score are the most important factors influencing the prognosis.

PMID- 29344154
TI  - Study of miR-10b regulatory mechanism for epithelial-mesenchymal transition,
      invasion and migration in nasopharyngeal carcinoma cells.
AB  - The aim of the study was to investigate the miR-10b regulatory mechanism for
      epithelial-mesenchymal transition (EMT) and its effect on the proliferation and
      migration of nasopharyngeal carcinoma cells. RT-qPCR was used to detect the
      expression of miR-10b in CNE1 nasopharyngeal carcinoma cell line. The NP69
      nasopharyngeal mucosal cell line was used to determine the expression of miR-10b
      after infection with lentivirus. The effect of miR-10b on the proliferation of
      NP69 was examined using cell counting kit-8. The effect of miR-10b on NP69
      migration was examined using scratch assay. Western blot analysis was used to
      detect the effects of miR-10b on the expression of epithelial cell markers E
      cadherin and beta-catenin and mesenchymal cell markers fibronectin, N-cadherin,
      vimentin and matrix metalloproteinase-9 (MMP-9). The present study showed that
      miR-10b was highly expressed in CNE1 cells. The stable expression of miR-10b
      promoted the proliferation and migration of NP69 cells, downregulated the
      expression of epithelial cell markers E-cadherin and beta-catenin, and
      upregulated the expression of mesenchymal cell markers fibronectin, N-cadherin,
      vimentin and MMP-9 resulting in cell EMT. In conclusion, miR-10b promotes the
      proliferation and migration of nasopharyngeal carcinoma cells, and induces EMT in
      nasopharyngeal carcinoma cells, thereby having the potential to become a new
      target for the treatment of nasopharyngeal carcinoma.

PMID- 29344155
TI  - CD133 mediates the TGF-beta1-induced activation of the PI3K/ERK/P70S6K signaling
      pathway in gastric cancer cells.
AB  - Cluster of differentiation (CD)133 has been reported to be involved in the
      activation of the extracellular signal-regulated kinase (ERK) signaling pathway
      in different types of cancer cells. CD133 has been reported to be involved in the
      activation of the ERK signaling pathway in various cancer cells. Transforming
      growth factor (TGF)-beta1 has also been reported to mediate the activation of the
      ERK signaling pathway. In addition, TGF-beta1 has been previously shown to
      mediate the activation of the ERK signaling pathway. Hence, the present study
      investigated the function of CD133 in the TGF-beta1-induced activation of the
      ERK/P70S6K signaling pathway in human gastric cancer (GC) cells. To this end, GC
      cell lines SGC7901 and MKN45 were treated with TGF-beta1. The expression of
      CD133, phospho-ERK (p-ERK) and phospho-P70S6 kinase (p-P70S6K) was upregulated in
      the cells treated with TGF-beta1, while the expression of ERK and P70S6K was not
      altered. To investigate whether CD133 is involved in the TGF-beta1-induced
      activation of the ERK/P70S6K signaling pathway in GC cells, immunomagnetic cell
      sorting was employed to isolate CD133+ GC cells, and a CD133-expression construct
      or CD133-targeting small interfering ribonucleic acids were transfected into
      cells to modulate the expression of CD133. Subsequently, the expression of CD133,
      ERK, p-ERK, P70S6K, and p-P70S6K was analyzed by western blotting. The CD133+
      cells displayed a high expression of p-ERK and p-P70S6K. Furthermore, SGC7901 GC
      cells were treated with U0126, an inhibitor of the ERK signaling pathway, to
      assess whether CD133 is upstream of ERK/P70S6K. The results showed that the
      expression of p-ERK and p-P70S6K was downregulated in the cells treated with
      U0126, while the expression of CD133 remained unaltered. The above preliminary
      results showed that CD133 likely mediates the TGF-beta1-induced activation of the
      ERK/P70S6K signaling pathway in human GC cells. To further understand the
      mechanism of regulation of the ERK/P70S6K signaling pathway by CD133, the
      expression of CD133 was modulated by transfecting cells with CD133-expression
      constructs or CD133-targeting small interfering ribonucleic acids. Results
      indicated that overexpression and silencing of CD133 directly increased and
      decreased the expression of p-ERK and p-P70S6K, respectively. Therefore, we
      hypothesized that CD133 mediates the TGF-beta1-induced activation of the
      PI3K/ERK/P70S6K signaling pathway in human GC cells.

PMID- 29344156
TI  - Effects of syndecan-1 on the expression of syntenin and the migration of U251
      glioma cells.
AB  - Glioma is the most frequently occuring primary brain tumor. Syndecan-1 (SDC1)
      expression is related to poor prognosis of numerous human malignancies including
      glioma. Syndecan binding protein (SDCBP) is an important partner for SDC1. The
      present study investigated whether SDC1 and SDCBP are expressed in glioma and
      their functions on glioma cell migration. An immunohistochemical assay revealed
      that SDC1 and SDCBP were expressed and were positively related to malignant level
      of glioma (SDC1, rs=0.576, P=0.001; SDCBP, rs=0.661, P<0.001). Moreover, the
      protein levels of SDC1 were positively correlated with those of SDCBP in glioma
      tissues (rs=0.628, P=0.001). In U251 glioma cells, protein levels of SDC1 and
      SDCBP were both upregulated in U251 cells with SDC1 overexpression, while
      downregulated with SDC1 knockdown. Transwell assay and scratch-wound healing
      assay showed that SDC1 overexpression significantly increased U251 cell
      migration, while SDC1 knockdown had the opposite effects. Rac1 activity, signal
      transducer and activator of transcription 3 (STAT3) phosphorylation, as well as
      expression of matrix metalloproteinase 2 (MMP2) and MMP9 was significantly
      increased by SDC1 overexpression, while was decreased by SDC1 knockdown. In
      conclusion, SDC1 overexpression upregulated SDCBP expression, and promoted glioma
      cell migration via Rac1 activation.

PMID- 29344157
TI  - Expression and clinical significance of programmed death-1 on lymphocytes and
      programmed death ligand-1 on monocytes in the peripheral blood of patients with
      cervical cancer.
AB  - The programmed death-1 (PD-1) signaling pathway serves a critical role in immune
      regulation and tolerance by suppressing the activation and proliferation of T
      cells. The aim of the present study was to investigate the effect of PD-1 and
      programmed death-ligand 1 (PD-L1) on the development of cervical carcinoma and
      cervical intraepithelial neoplasia (CIN). A total of 40 healthy controls (HC), 40
      patients with CIN and 66 newly diagnosed cervical cancer patients were recruited.
      The expression level of PD-1 expression on peripheral cluster of differentiation
      (CD)4+ and CD8+ T cells and PD-L1 on monocytes was analyzed by flow cytometry.
      The expression level of soluble PD-L1 in serum was determined by an ELISA. The
      results of the present study demonstrated that the PD-1 expression level on CD4+
      and CD8+ T cells was significantly increased in CIN and cervical cancer, compared
      with that in HC. In addition, the PD-1 expression level on CD4+ and CD8+ T cells
      was increased in cervical cancer, compared with that in CIN. However, the
      expression level of PDL-1 on CD14+ monocytes was increased in cancer and CIN, but
      limited in cancer and CIN. In addition, PD-1 expression on CD4+ T cells was
      positively associated with PD-1 expression on CD8+ T cells in cervical cancer
      (P<0.05). Further analyses revealed that the proportion of PD-1 on CD4+ and CD8+
      T cells were positively associated with tumor stages. However, no difference in
      the degree of soluble PD-1 among cancer, CIN and HC cells was revealed. The
      results suggested that the PD-1 signaling pathway is involved in the development
      of CIN and cervical cancer.

PMID- 29344158
TI  - Construction of the POT1 promoter report gene vector, and the effect and
      underlying mechanism of the POT1 promoter in regulating telomerase and telomere
      length.
AB  - By using human genomic DNA as a template to clone protection of telomere 1 (POT1)
      promoter gene segments and construct the POT1 promoter luciferase report gene
      vector (pGL3-Control-POT1-promoter), the association between POT1, and the
      regulation of telomerase and telomere length was investigated. In the present
      study, two recombinant luciferase report gene vectors were constructed, which
      included different regions of the POT1 promoter. The plasmids were transformed
      into DH5alpha and the positive clones were obtained. The two plasmids termed as
      pGL3-Control-POT1-promoter-1 and pGL3-Control-POT1-promoter-2, were confirmed
      using restriction enzyme analysis and sequencing. They were separately and
      transiently transfected into four types of human tumor cells (A549, H460, HepG2
      and HeLa). The transcriptional activities of the POT1 promoter were verified
      using the dual-luciferase assay. The relative expression of POT1 and human
      telomerase reverse transcriptase (hTERT), and telomere length were analyzed using
      quantitative polymerase chain reaction in the four types of non-transfected tumor
      cells. Using SPSS software, correlations between POT1 promoter activity, and POT1
      expression, hTERT expression and telomere length were analyzed. Two POT1 promoter
      fragments (POT1-promoter-1 and -2) were successfully constructed into the pGL3
      Control luciferase report gene vector. POT1-promoter-1 exhibited significantly
      stronger transcription activity compared with POT1-promoter-2. The results of the
      partial correlation and linear regression analyses were similar: POT1 promoter
      activity was identified to be significantly and positively correlated with POT1
      expression and telomere length (partial correlation coefficients, both P<0.05;
      linear regression, both P<0.01). However, POT1 promoter activity and hTERT
      expression were significantly negatively correlated (both P<0.05). The results
      obtained in the present study suggest that the POT1 promoter influences telomere
      length. Furthermore, these data indicated that POT1 promoter activity and POT1,
      as well as telomere length, may be a useful biomarker for tumor detection and
      future patient prognosis.

PMID- 29344159
TI  - p38 predicts depression and poor outcome in esophageal cancer.
AB  - p38 mitogen-activated protein kinase (MAPK) signaling has been implicated in the
      cancer development and progression. However, the precise mechanism of this
      association remains unknown. The aim of the present study was to evaluate the
      association between p38 and cancer progression, including investigations into the
      effects on cell proliferation, resistance to thalidomide, indoleamine 2,3
      dioxygenase (IDO) expression and prognosis in patients with esophageal cancer.
      The present retrospective study included patients with stage I-III esophageal
      cancer. A total of 228 patients with esophageal cancer were recruited to analyze
      the expression of phosphorylated (p)-p38 and IDO in tumor, and normal tissues
      through immunohistochemistry. Depression status was measured using the Zung Self
      Rating Depression Scale. P38 cDNA was transfected into esophageal cancer cells to
      assess tumor cell viability, sensitivity to thalidomide treatment and IDO gene
      expression. Western blotting and flow cytometry was used to analyze protein
      expression alterations, and apoptosis in esophageal cancer cells. P-p38 protein
      was expressed in 68.9% of cancer tissues, and was significantly associated with
      depressive symptoms, tumor recurrence and poor survival of patients. In vitro
      experiments revealed that the expression of p-p38 induced esophageal cancer Eca
      109 and TE-1 cell viability, and resistance to thalidomide treatment, as well as
      in the expression of IDO without the application of lipopolysaccharides. Further
      follow-up of patients revealed that depression was also an independent factor for
      early recurrence and overall survival rate. Altered p38 MAPK expression was
      associated with poor outcome in patients with esophageal cancer. p38 may be a
      potential biomarker for the prediction of depressive symptoms and prognosis in
      patients with esophageal cancer.

PMID- 29344160
TI  - The role of computed tomography and magnetic resonance imaging in diagnosing
      clear cell ameloblastoma: A case report.
AB  - Ameloblastoma is the most common and clinically relevant type of odontogenic
      tumor. Clear cell odontogenic carcinoma is histologically characterized by solid
      sheets and nests of clear cells, whereas clear cell ameloblastoma (CCAM) is
      histologically characterized by an ameloblastomatous component intermixed with an
      extensive clear cell component. A total of 12 reports have been published on the
      histological etiology for CCAM; however, no reports have made regarding the
      detailed computed tomography and/or magnetic resonance imaging features of tumors
      of this type. The present study describes a case of a well-circumscribed 20-mm
      radiolucent lesion of the anterior mandible that was misdiagnosed as a clear cell
      odontogenic carcinoma. The study describes the detailed radiological
      characteristics of a case of CCAM.

PMID- 29344161
TI  - UVB radiation represses CYLD expression in melanocytes.
AB  - CYLD lysine 63 deubiquitinase (CYLD) was originally identified as a tumor
      suppressor that is mutated in familial cylindromatosis. Unlike in
      cylindromatosis, downregulation of the deubiquitinase CYLD in melanoma, a highly
      aggressive tumor, is not caused by mutations in the CYLD gene, but rather by a
      constitutive and high expression of the snail family transcriptional repressor 1
      (SNAIL1). A reduced CYLD level leads to B-cell lymphoma-3/p50/p52-dependent
      nuclear factor-kappaB activation, which in turn triggers the expression of genes
      such as cyclin D1 and N-cadherin. Elevated levels of cyclin D1 and N-cadherin
      promote melanoma proliferation and invasion. By analyzing the regulation of CYLD
      expression in melanocytes, the present study identified a signaling pathway that
      is regulated in response to ultraviolet B (UVB) radiation in melanocytes. UVB
      light leads to an extracellular signal-regulated kinase-mediated induction of
      SNAIL1 and subsequent downregulation of CYLD expression in normal human
      epithelial melanocytes. The UVB-mediated suppression of CYLD in melanocytes may
      have a key role in the reaction to UV stimuli, and may also potentially be
      involved in the early malignant transformation processes.

PMID- 29344162
TI  - Effects of rat bone marrow-derived mesenchymal stem cells on breast cancer cells
      with differing hormone receptor status.
AB  - Breast cancer is a heterogeneous disease that can be classified into several
      molecular intrinsic subtypes according to hormone markers, including estrogen
      receptor, progesterone receptor and human epidermal growth factor receptor-2.
      Breast cancer cases with different hormone status vary with respect to patient
      morbidity, metastasis organotropism and disease progression. It is well known
      that the most preferential relapse site of breast cancer is in the bone, but the
      metastatic incidence is markedly higher in hormone receptor-positive cancer
      compared with that in hormone receptor-negative cancers. Bone marrow-derived
      mesenchymal stem cells (BMSCs) perform important roles at the site of metastasis;
      however, the effects in different tumors or tumor subtypes are controversial. The
      present study aimed to explore the various effects of BMSCs on the biological
      characteristics of different hormone receptor statuses. BMSCs were obtained from
      female rats and characterized by cell lineage-specific antigens. The MCF-7 and
      MDA-MB-231 breast cancer cell lines, which are hormone receptor-positive and 
      negative, respectively, were employed in the present study. The cancer cells were
      co-cultured with BMSCs, and changes in the biological characteristic of cell
      growth, apoptosis, migration and epithelial-mesenchymal transition (EMT) were
      assessed. BMSCs exhibited chemotactic attraction to MCF-7, promoted the
      proliferation of MCF-7 cells and reduced MCF-7 cell apoptosis. By contrast, BMSCs
      exerted no marked effects on these behaviors of MDA-MB-231 cells. However,
      following co-culture with BMSCs, the migratory ability was enhanced in the two
      cell lines. Furthermore, the expression of epithelial markers (epithelial
      cadherin and occludin) was decreased, and mesenchymal marker vimentin was
      markedly increased in the two cell lines. Notably, the migratory ability of MDA
      MB-231 cells was attenuated compared with that of MCF-7 cells. The results from
      the present study indicated that BMSCs may favor receptor-positive cancer cell
      proliferation in bone and promote enhanced invasiveness of receptor-negative
      compared with receptor-positive cancer cells.

PMID- 29344163
TI  - Clinical characteristics and treatment outcomes of parathyroid carcinoma: A
      retrospective review of 234 cases.
AB  - Parathyroid carcinoma (PC) is one of the rarest known types of cancer and has a
      moderate prognosis, with estimated 5- and 10-year overall survival rates between
      78-85% and between 49-70%, respectively. To raise awareness of this disease, and
      to optimize its diagnosis, clinical management and prognosis, the present study
      retrospectively reviewed 234 cases of PC. A total of 226 cases of PC, which were
      archived between 1984 and 2015 in the three major databases of the Chinese
      population, were retrieved and pooled with the 8 cases diagnosed and treated at
      the Department of Thyroid Surgery of The First Hospital of Jilin University
      (Changchun, China) between June 2008 and December 2015. The clinicopathological
      features, diagnosis, surgical procedures and outcomes of these cases of PC were
      investigated. The review revealed that misdiagnosis has been a considerable
      issue, with >80% of the patients misdiagnosed prior to surgery, and the accuracy
      of intraoperative diagnosis based on frozen sections was only 15.04%. The use of
      radical resection as first-line therapy significantly improved the disease-free
      survival by ~8 years (log-rank, 20.956; P<0.001); and, at relapse, reoperation
      prolonged patient survival by ~7 years (log-rank, 35.322; P<0.001). Consistently,
      a Cox proportional hazards analysis indicated that radical resection as a first
      line therapy reduced the risk of postoperative recurrence (P=0.030), and that
      reoperation following recurrence significantly improved patient survival
      (P=0.030). The 5- and 10-year cumulative disease-specific survival rates of the
      cases of PC were 83 and 67%, respectively. Notably, an increased mortality rate
      was observed among males with PC compared with female patients with PC. In
      summary, in the past 32 years (1984-2015), the majority of patients with PC have
      been misdiagnosed. Performing radical resection as the first-line therapy
      significantly reduces recurrence and improves patient survival time; and,
      following relapse, subsequent surgery has also been demonstrated to be an
      effective approach.

PMID- 29344164
TI  - Mastl overexpression is associated with epithelial to mesenchymal transition and
      predicts a poor clinical outcome in gastric cancer.
AB  - Microtubule-associated serine/threonine kinase like (Mastl) is deregulated in a
      number of types of human malignancy and may be a kinase target for cancer
      treatment. The aim of the present study was to determine the Mastl expression in
      gastric cancer and to clarify its clinical and prognostic significance.
      Immunohistochemistry was performed on a cohort of 126 postoperative gastric
      cancer samples to detect the expression of Mastl and two epithelial to
      mesenchymal transition (EMT) markers, epithelial-cadherin and Vimentin. The chi2
      test, Kaplan-Meier estimator analysis and Cox's regression model were used to
      analyze the data. Upregulated Mastl protein expression was observed in the
      gastric cancer tissues compared with that in the adjacent non-cancerous gastric
      tissues. Increased Mastl expression was identified in 54/126 (42.9%) gastric
      cancer samples, and was significantly associated with lymph node metastasis,
      tumor relapse, EMT status and poor overall survival. Additional analysis
      demonstrated that the Mastl expression level stratified the patient outcome in
      stage III, but not stage II tumor subgroups. Cox's regression analysis revealed
      that increased Mastl expression was an independent prognostic factor for patients
      with gastric cancer. Mastl expression may be a valuable prognostic marker and a
      potential target for patients with gastric cancer.

PMID- 29344165
TI  - Overexpression of forkhead box M1 and urokinase-type plasminogen activator in
      gastric cancer is associated with cancer progression and poor prognosis.
AB  - Forkhead box M1 (FOXM1) and urokinase-type plasminogen activator (uPA) are
      overexpressed and associated with the pathogenesis of multiple types of human
      malignancy. The aims of the present study were to investigate FOXM1 and uPA
      expression levels in human gastric cancer using tissue microarray techniques;
      determining their association with clinicopathological characteristics as well as
      their prognostic value. Tissue microarray blocks, comprising 436 gastric cancer
      cases and 92 non-cancerous adjacent normal gastric tissues, were analyzed for
      FOXM1 and uPA protein expression levels using immunohistochemistry. The results
      were analyzed statistically in association with various clinicopathological
      characteristics and overall survival rates. FOXM1 and uPA were detected in 78.67
      (343/436) and 83.26% (363/436) of cancer samples, respectively. FOXM1 and uPA
      were not expressed in the 92 normal gastric tissue samples. In gastric cancer,
      FOXM1 and uPA levels were associated with tumor size, depth of invasion, tumor
      node-metastasis (TNM) stage, lymph node metastasis, vessel invasion and distant
      metastases. The overall survival rate was significantly decreased in patients
      expressing FOXM1 and uPA compared with FOXM1- and uPA-negative patients. Coxs
      multivariate analysis revealed that age, depth of invasion and expression levels
      of FOXM1 and uPA are independent predictors of survival in patients with gastric
      cancer. These results indicated that increased FOXM1 and uPA expression levels
      are associated with the invasive and metastatic processes in human gastric
      cancer, and inversely associated with patient prognosis. Therefore, FOXM1 and uPA
      may serve as novel prognostic markers independent of, but supplementing, the TNM
      staging system.

PMID- 29344166
TI  - Identification and functional analysis of risk-related microRNAs for the
      prognosis of patients with bladder urothelial carcinoma.
AB  - The aim of the present study was to investigate risk-related microRNAs (miRs) for
      bladder urothelial carcinoma (BUC) prognosis. Clinical and microRNA expression
      data downloaded from the Cancer Genome Atlas were utilized for survival analysis.
      Risk factor estimation was performed using Cox's proportional regression
      analysis. A microRNA-regulated target gene network was constructed and presented
      using Cytoscape. In addition, the Database for Annotation, Visualization and
      Integrated Discovery was used for Gene Ontology (GO) and Kyoto Encyclopedia of
      Genes and Genomes pathway enrichment, followed by protein-protein interaction
      (PPI) network analysis. Finally, the K-clique method was applied to analyze sub
      pathways. A total of 16 significant microRNAs, including hsa-miR-3622a and hsa
      miR-29a, were identified (P<0.05). Following Cox's proportional regression
      analysis, hsa-miR-29a was screened as a prognostic marker of BUC risk (P=0.0449).
      A regulation network of hsa-miR-29a comprising 417 target genes was constructed.
      These target genes were primarily enriched in GO terms, including collagen fibril
      organization, extracellular matrix (ECM) organization and pathways, such as focal
      adhesion (P<0.05). A PPI network including 197 genes and 510 interactions, was
      constructed. The top 21 genes in the network module were enriched in GO terms,
      including collagen fibril organization and pathways, such as ECM receptor
      interaction (P<0.05). Finally, 4 sub-pathways of cysteine and methionine
      metabolism, including paths 00270_4, 00270_1, 00270_2 and 00270_5, were obtained
      (P<0.01) and identified to be enriched through DNA (cytosine-5)-methyltransferase
      (DNMT)3A, DNMT3B, methionine adenosyltransferase 2alpha (MAT2A) and spermine
      synthase (SMS). The identified microRNAs, particularly hsa-miR-29a and its 4
      associated target genes DNMT3A, DNMT3B, MAT2A and SMS, may participate in the
      prognostic risk mechanism of BUC.

PMID- 29344167
TI  - Analysis of IMP3 expression in primary tumor and stromal cells in patients with
      colorectal cancer.
AB  - Insulin-like growth factor II mRNA-binding protein 3 (IMP3) is an oncofetal
      protein upregulated in tumor cells during carcinogenesis. The aim of the present
      study was to investigate the expression status of IMP3 in colorectal cancer (CRC)
      tissues and its clinical significance. Immunostaining was performed in 130 CRC
      samples, the association of IMP3 expression with clinicopathological
      characteristics was assessed and 58 patients were selected for survival analysis.
      To the best of our knowledge, the present study describes for the first time the
      expression of IMP3 in tumor stromal components of CRC. Stromal expression of IMP3
      was detected in 24/130 (18.5%) CRC tissue specimens and was associated with tumor
      node-metastasis (TNM) stage (stage III-IV, P=0.003), lymph node metastasis
      (P=0.006), lympho-vascular invasion (P=0.003), tumor border (P=0.013). Tumoral
      expression of IMP3 was detected in 94/130 (72.3%) of CRC specimens and was
      associated with T classification (T3-T4, P=0.027), tumor-node-metastasis (TNM)
      stage (stage III-IV, P=0.011), lymph node metastasis (P=0.048), tumor budding
      (>10 buds, P=0.005). Further study indicated that patients with IMP3 expressed in
      tumor cells and tumor stroma tend to have poorer overall survival rates (P=0.02
      and P=0.06, respectively). Moreover, tumoral expression of IMP3 and TNM stage
      were identified to be independent prognostic factors in CRC. IMP3 was not only
      expressed in tumor cells but also in stroma cells. Stromal expression of IMP3 was
      associated with lymph node metastasis and advanced tumor TNM stage. Moreover, the
      survival analysis indicated that there is a significant association between IMP3
      expression in tumor cells and a poorer overall survival rate in patients with
      CRC. The expression of IMP3 maybe a predicted factor for CRC patient.

PMID- 29344168
TI  - MiR-124 inhibits invasion and induces apoptosis of ovarian cancer cells by
      targeting programmed cell death 6.
AB  - Epithelial ovarian cancer remains the most common type of malignant tumor of the
      female reproductive system worldwide. Routine surgery and chemotherapy are the
      best treatments available for patients with ovarian cancer; however, almost 40%
      of ovarian cancer cases are intractable, with poor 5-year survival rates.
      MicroRNAs (miRNA) are endogenous small non-coding RNA molecules that function in
      transcriptional and post-transcriptional regulation of gene expression in various
      cellular processes. Recent studies demonstrated that microRNA (miR)-124 was
      downregulated in numerous types of tumors; however, the function and mechanism
      underlying miR-124 in epithelial ovarian cancer remain unclear. The present study
      revealed that miR-124 may be significantly downregulated in epithelial ovarian
      cancer. Using prediction algorithms and luciferase reporter gene assays, the
      present study identified and confirmed programmed cell death 6 (PDCD6) as a
      novel, direct target of miR-124. Overexpression of miR-124 suppressed PDCD6
      expression, inhibited cell proliferation, migration and invasion, and induced
      apoptosis in SKOV3 and OCVAR3 cells in vitro. In the present study,
      overexpression of PDCD6 in epithelial ovarian cancer cells co-transfected with
      miR-124 effectively reversed the miR-124-induced apoptosis. Therefore, the
      results of the present study suggested that miR-124 is a tumor suppressor miRNA
      and a potential target for future treatment of ovarian malignant neoplasms.

PMID- 29344169
TI  - Bortezomib overcomes the negative prognostic impact of renal impairment in a
      newly diagnosed elderly patient with multiple myeloma: A case report.
AB  - Multiple myeloma (MM) is a common B-cell hematological malignancy in the clinic.
      Bortezomib is the first-in-class proteasome inhibitor that has been approved for
      the treatment of patients with MM in the bone marrow. The present study report
      the case of an 83-year-old man who showed marked weakness, fatigue and a poor
      appetite. The patient was admitted to the Department of Nephrology due to severe
      renal impairment (RI). Immunofixation electrophoresis indicated a lambda light
      chain-positive status. There were 19.2% plasmablasts and proplasmacytes in the
      bone marrow. Positivity for the cell surface markers cluster of differentiation
      (CD)13, CD33, CD38 and human leukocyte antigen-antigen D-related was detected by
      flow cytometry. The patient was diagnosed with MM, lambda light chain type, stage
      IIIB, and received bortezomib and dexamethasone regimen chemotherapy. RI was
      improved following the chemotherapy, and plasmablasts and proplasmacytes were
      almost eliminated. The Hb level was maintained at ~90 g/l. Overall, the present
      case report suggests that bortezomib may be safe and effective for elderly
      patients, even those >80 years of age, with severe RI.

PMID- 29344170
TI  - Phosphorylation of Ser6 in hnRNPA1 by S6K2 regulates glucose metabolism and cell
      growth in colorectal cancer.
AB  - Abnormal glucose metabolism is critical in colorectal cancer (CRC) development.
      Expression of the pyruvate kinase (PK) M2 isoform, rather than the PKM1 isoform,
      serves important functions in reprogramming the glucose metabolism of cancer
      cells. Preferential expression of PKM2 is primarily driven by alternative
      splicing, which is coordinated by a group of splicing factors including
      heterogeneous nuclear ribonucleoprotein (hnRNP)A1, hnRNPA2 and RNA binding motif
      containing. However, the underlying molecular mechanisms associated with cancer
      cell expression of PKM2, instead of PKM1, remain unknown. The mRNA levels of PKM
      isoform and glucose metabolism were analyzed in CRC cells. The results of the
      present study indicated that S6 kinase 2 (S6K2) promotes glycolysis and growth of
      CRC cells by regulating alternative splicing of the PKM gene. In addition,
      chromatin immunoprecipitation assay indicated that S6K2 phosphorylation of Ser6
      of hnRNPA1 facilitated hnRNPA1 binding to the splicing site of the PKM gene. As a
      result, cancer cells preferentially expressed the PKM2 isoform, instead of the
      PKM1 isoform. Furthermore, Cox regression analysis demonstrated that the
      phosphorylation of Ser6 of hnRNPA1 was a predictor of poor prognosis for patients
      with CRC. Therefore, the results of the present study revealed that the
      phosphorylation of Ser6 in hnRNPA1 by S6K2 was a novel mechanism underlying
      glucose metabolic reprogramming, and suggested that S6K2 is a potential
      therapeutic target for CRC treatment.

PMID- 29344171
TI  - DEPDC7 inhibits cell proliferation, migration and invasion in hepatoma cells.
AB  - DEP Domain Containing 7 (DEPDC7) is highly and specifically expressed in normal
      liver tissue, belonging to the class of genes of liver-selective cell
      communication. Although the function of DEPDC7 remains poorly understood, its
      expression is decreased in liver cancer compared with normal liver tissues. It
      has previously been demonstrated that knockdown of DEPDC7 promotes cell growth, S
      phase entry and cell mobility and invasion in HepG2 cells. In the present study,
      it was shown that DEPDC7 expression is downregulated in four hepatoma cell lines
      (SMMC-7721, Huh-7, SK-Hep-1 and HepG2) and 48 hepatoma tissues, determined using
      western blot and immunohistochemical analysis. When DEPDC7 is overexpressed in
      hepatoma cell lines (SK-Hep-1 and Huh-7), it inhibits cell proliferation and cell
      growth; inhibits cell cycle entry; and inhibits cell motility and invasion. These
      results, together with the results of knockdown experiments, demonstrate that
      DEPDC7 may have an important role in hepatoma cells growth and metastasis and
      suggest it could be a therapeutic target; however, in vitro studies are required
      to validate this hypothesis.

PMID- 29344172
TI  - Potential factors influencing the development of oral tongue squamous cell
      carcinoma in young mature patients: Lingual position of the mandibular second
      molar and narrow tongue space.
AB  - The lingual position of the mandibular second molar and narrow tongue space are
      associated with oral tongue squamous cell carcinoma (OTSCC) development in young
      mature patients. The present study aimed to assess the role of the mandibular
      second molar position and tongue space in young mature patients with OTSCC. The
      medical records of 21 patients with OTSCC aged <50 years, who had an intact
      mandibular second molar and had undergone computed tomography (CT) imaging
      between April 2009 and December 2015 at the Section of Maxillofacial Surgery in
      Tokyo Medical and Dental University, were retrospectively examined. As controls,
      21 sex-matched patients of a similar age to the patients in the OTSCC group, and
      with a height and weight within 5% of those of the OTSCC group, were collected.
      The location of the mandibular second molar on the affected side and area of the
      tongue space were determined using coronal and axial CT images. Mann-Whitney U
      test analysis revealed that the location of the mandibular second molar and the
      area of the tongue space differed significantly between young mature patients
      with OTSCC and the controls. The present study thus revealed that the lingual
      position of the mandibular second molar and the narrow tongue space may be
      potential factors influencing OTSCC development in young maturity.

PMID- 29344173
TI  - RASAL1 inhibits HepG2 cell growth via HIF-2alpha mediated gluconeogenesis.
AB  - RAS protein activator like 1 (RASAL1) is a member of the RAS GTPase-activating
      protein (GAP) family, and has been identified as a tumor suppressor in various
      types of cancer. In the present study, it was determined that decreased levels of
      RASAL1 were accompanied by a higher pathological stage and larger tumor size in
      human liver cancer. Therefore, it was hypothesized that RASAL1 may serve an
      inhibitory role in liver cancer. In the present study, the following was
      demonstrated: i) Exogenous expression of RASAL1 may inhibit the proliferation and
      invasion ability of HepG2 cells; ii) overexpression of RASAL1 may downregulate
      HIF-2alpha transcription activity and HIF-2alpha-mediated gluconeogenesis through
      extracellular signal-related kinase 1/2 activation; iii) RASAL1 may reduce the
      xenograft tumor size in nude mice by inhibiting the expression of hypoxia
      inducible factor (HIF)-2alpha and gluconeogenesis enzymes. These data suggest
      that the RASAL1/HIF-2alpha axis may serve an essential role in the growth of
      HepG2 cells, and that this signaling cascade may be a novel therapeutic target
      for the treatment of liver cancer.

PMID- 29344174
TI  - Expression profile of cytokines in gastric cancer patients using proteomic
      antibody microarray.
AB  - Gastric cancer (GC) is often a deadly disease due to the late diagnosis and
      chemoresistance that characterizes many cases of this disease. The aim of this
      study was to explore a panel of candidate cytokines as diagnostic and predictive
      biomarkers for GC. Sixteen tissue samples of GC and adjacent noncancerous mucosa
      were selected from GC patients (n=8) for antibody microarray analysis. Proteomic
      chip-based analysis was performed to simultaneously identify 507 cytokines using
      a cytokine antibody array in the gastric tissues to screen for differential
      proteins related in cases of GC. Fold changes of protein expression >2.0 or <0.5
      were considered significant. The proteins that showed significant differences in
      levels between the cancerous and non-cancerous samples were analyzed using
      bioinformatics analysis. One hundred and five cytokines that were significantly
      different (p<0.05) between GC tissues and normal gastric mucosa were identified.
      Gene Ontology (GO) enrichment analysis showed that these differentially expressed
      proteins are involved in many biological and immunological processes, mainly in
      response to stress, chloroplast thylakoid membrane, vacuole, photosynthesis,
      aspartic-type endopeptidase activity and flavin adenine dinucleotide binding.
      Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that
      these proteins mainly were involved in the process of cytokine-cytokine receptor
      interaction, transforming growth factor-beta (TGF-beta) signaling pathway,
      pathways in cancer, tumor necrosis factor (TNF) signaling pathway, and mitogen
      activated protein kinase (MAPK) signaling pathway. These findings suggest that
      the differentially expressed proteins could be associated with GC in patients.
      Further study of these cytokines may provide a promising approach for diagnosis,
      classification and prognosis of GC.

PMID- 29344175
TI  - Effects of andrographolide on postoperative cognitive dysfunction and the
      association with NF-kappaB/MAPK pathway.
AB  - The present study investigated the effects of andrographolide on postoperative
      cognitive dysfunction (POCD) in aged rats to gain insight of the underlying
      mechanism, which may provide theoretical basis for the clinical application of
      andrographolide to prevent POCD in older patients. Thirty aged male rats were
      randomly assigned to 3 groups: Control, model and andrographolide groups. The
      Morris water maze test was used to examine the spatial memory and learning
      ability of the rats postoperatively. The histological alterations of neuronal
      cells in the hippocampus were visualized by H&E staining. The serum levels of
      neuron-specific enolase (NSE), human soluble protein-100beta (S-100beta) and the
      inflammation factors of interluekin (IL)-1beta, IL-6 and TNF-alpha involved in
      the nuclear factor kappaB (NF-kappaB)/mitogen-activated protein kinase (MAPK)
      signaling pathway were detected by ELISA. The NF-kappaB/MAPK signaling pathway
      associated proteins in rat serum were detected by western blotting. Following
      andrographolide treatment, the rats significantly gained learning ability after
      surgery. Is it ameliorated hippocampal neuronal injury in rats following surgery.
      Andrographolide decreased NSE, S-100beta, and the inflammation factors, IL-6, IL
      1beta and TNF-alpha in serum. Andrographolide reduced NF-kappaB/MAPK pathway
      associated protein expression. Andrographolide ameliorated POCD in aged rats
      following surgery. The underlying mechanism may be associated with the
      downregulation the inflammatory factors and NF-kappaB/MAPK-associated protein
      expression.

PMID- 29344176
TI  - Effect of fraxetin on proliferation and apoptosis in breast cancer cells.
AB  - The aim of the present study was to examine the effect of fraxetin on
      proliferation and apoptosis in the MCF-7 breast cancer cell line. Cell
      proliferation was measused using an MTT assay and 4',6-diamidino-2-phenylindole
      (DAPI) staining was used to determine shrinkage and condensation. RT-PCR was used
      to examine the expression of factor-associated suicide (Fas) and Fas ligand
      (FasL) mRNA, and western blot analysis was used to examine Bax and Bcl-2 protein.
      MTT showed that the proliferation of MCF-7 cells was significantly inhibited by
      fraxetin in a dose-dependent manner. Fraxetin also induced significant
      morphological changes of MCF-7 cells, suggestive of apoptosis, whereas DAPI
      staining showed that fraxetin caused cell shrinkage and chromatin condensation.
      RT-PCR showed that the expression of Fas and FasL mRNA was upregulated by
      fraxetin and the western blot analysis revealed that Bax was upregulated and Bcl
      2 was downregulated. In conclusion, fraxetin can inhibit the proliferation of MCF
      7 cells, induce apoptosis, upregulate Fas, FasL and Bax, and downregulate Bcl-2
      to induce apoptosis. These results support the potential therapeutic role for
      fraxetin in breast cancer.

PMID- 29344177
TI  - Characteristics of nosocomial infection and its effects on the survival of
      chemotherapy patients with advanced non-small cell lung cancer.
AB  - The present study was planned to investigate the characteristics of nosocomial
      infection and its effects on the survival in advanced non-small cell lung cancer
      (NSCLC) patients. Retrospective analysis was performed for the 169 chemotherapy
      patients with NSCLC and nosocomial infection during hospitalization in Binzhou
      City Central Hospital from March, 2013 to January, 2015. In addition, 170
      patients without nosocomial infection were also involved as a control group. The
      distribution of major drug resistance of Gram-negative (G-) and Gram-positive
      (G+) were analyzed. The survival conditions of the patients were analyzed
      according to the nosocomial infection occurrence. The risk factors of nosocomial
      infection in patients with NSCLC were analyzed by univariate and multivariate
      logistic analysis. The percentage of G+ infection was 45.6% while G- infection
      was 54.4%. Nosocomial infections were most common in respiratory system. The
      median survival time of the observation group was shorter than that of the
      control group (P<0.05). G- infection was the most common type of infection in
      nosocomial infection of the patients with NSCLC. The occurrence of infection
      seriously affected the survival time of patients. Attention is required to the
      patients older than 60 years undergoing treatment with glucocorticoids as well as
      immunosuppressive agents.

PMID- 29344178
TI  - Long non-coding RNA lncTCF7 activates the Wnt/beta-catenin pathway to promote
      metastasis and invasion in colorectal cancer.
AB  - Long non-coding RNA (Lnc)TCF7 is a novel lncRNA that is involved in
      tumorigenesis. Previous studies have revealed that lncTCF7 serves an essential
      role in maintaining cancer stem cell self-renewal; however, the functions of
      lncTCF7 in colorectal cancer (CRC) remain unknown. Therefore, the present study
      aimed to investigate the role of lncTCF7 in CRC. LncTCF7 was upregulated in 52/58
      CRC tissues, and its expression correlated with tumor size, lymph metastasis and
      tumor-node-metastasis stage in CRC. Knocking down lncTCF7 in colon cancer cell
      lines decreased cell proliferation, migration and invasion, while lncTCF7
      overexpression showed opposite changes. In addition, lncTCF7 promoted cell
      proliferation in vivo. LncTCF7 activated the Wnt/beta-catenin signaling pathway,
      which is essential for cancer development. Survival analysis revealed that
      patients with higher expression of lncTCF7 had significantly worse prognosis
      compared with patients with low expression. These findings indicate that lncTCF7
      regulates CRC progression and support the notion of lncTCF7 as a CRC prognostic
      marker.

PMID- 29344179
TI  - In vivo antitumor activity evaluation of cancer vaccines prepared by various
      antigen forms in a murine hepatocellular carcinoma model.
AB  - Cancer cell vaccines with strong specificity and low tolerance have been revealed
      to be a promising option for oncology treatment. Various antigen forms, including
      tumor cell lysate and glutaraldehyde-fixed tumor cells, have been intensively
      used in cancer vaccine preparation. However, the most effective antigen form has
      not yet been identified. In the present study, the antitumor efficiency of
      vaccines prepared by these two antigen forms was systematically investigated.
      Murine H22 hepatocellular carcinoma cell lysate and glutaraldehyde-fixed H22
      hepatocellular carcinoma cells were conjugated with Freund's adjuvant to prepare
      vaccines, H22-TCL and Fixed-H22-CELL, respectively. H22-TCL and Fixed-H22-CELL
      were administrated by subcutaneous immunization in prophylactic and therapeutic
      strategies. The results of the present study revealed that H22-TCL immunization
      induced more significant inhibition on tumor growth and metastasis compared with
      Fixed-H22-CELL injection. Furthermore, histopathological observation demonstrated
      that H22-TCL vaccine induced larger areas of continuous necrosis within tumors
      compared to the Fixed-H22-CELL vaccine, which was associated with the extent of
      tumor inhibition. More importantly, the H22-TCL vaccine injection elicited more
      evident antigen-specific antibody responses compared with the Fixed-H22-CELL
      injection. Splenocytes from H22-TCL vaccinated mice also exhibited a more
      significant T lymphocytes proliferation compared with that from Fixed-H22-CELL
      treated mice. All the results indicated that whole tumor cell lysate may be a
      more effective antigen form in cancer vaccine preparation compared with
      glutaraldehyde-fixed tumor cells, which elicited more marked antigen specific
      humoral and cellular immune responses resulted with a superior antitumor
      efficiency. This would have important clinical signification for cancer vaccine
      preparation and serve a role in prompting this to other researchers.

PMID- 29344180
TI  - miR-493 inhibits proliferation and invasion in pancreatic cancer cells and
      inversely regulated hERG1 expression.
AB  - The human ether-a-go-go-related potassium channel 1 (hERG1) is a component of the
      voltage-gated Kv11.1 potassium channel, which has been recently indicated to have
      a crucial role in the tumorigenesis of multiple tumors, including pancreatic
      carcinoma. Pancreatic carcinoma is one of the most malignant human cancer types,
      which has an extremely poor prognosis. The present study demonstrated that the
      expression levels of hERG1 were markedly elevated in pancreatic cancer tissues
      and pancreatic cancer cell lines, and that the abnormal hERG1 expression was
      significantly associated with the proliferation and invasion ability of
      pancreatic cancer. Furthermore, hERG1 was identified to be a direct target of miR
      493, which is generally reduced in pancreatic cancer tissues and cell lines.
      These findings provide a novel insight into the regulatory mechanism of miR
      493/hERG1 in pancreatic cancer cell proliferation and invasion, which may aid the
      development of novel diagnostic and therapeutic strategies for pancreatic cancer
      in the future.

PMID- 29344181
TI  - L-type amino acid transporter 1 expression is upregulated and associated with
      cellular proliferation in colorectal cancer.
AB  - Previous studies have shown that the L-type amino acid transporter 1 (LAT1) is
      highly expressed in many types of cancer. Upregulated LAT1 expression is
      considered to be associated with cancer cell proliferation. In the present study,
      we investigated LAT1 expression in 210 patients with colorectal cancer (CRC) and
      40 patients with colonic adenoma using an immunohistochemical method, and
      analyzed the associations between LAT1 expression and clinicopathological factors
      and prognosis. The biological significance of LAT1 was also examined under
      conditions with sub-normal amounts of essential amino acids using colon cancer
      cell lines. High expression of LAT1 was observed in 152 of 210 CRC patients
      (72.4%) and 12 of 40 patients with colonic adenoma (30%), and this difference in
      the frequency of LAT1 expression between CRC and adenoma was significant
      (P<0.001). High expression of LAT1 was associated with venous invasion (P=0.027).
      The restriction of amino acids suppressed cell proliferation in CRC cells with
      higher LAT1 expression, while cellular proliferation was not suppressed in the
      cells expressing lower levels of LAT1. Mammalian target of rapamycin (mTOR)
      expression was also downregulated under restricted availability of amino acids,
      suggesting that the restriction of amino acids induced an antitumor effect
      through inhibition of the LAT1/mTOR pathway. In summary, the present study
      demonstrated that LAT1 expression is frequently upregulated in CRC and is
      associated with cancer cell proliferation via the mTOR pathway.

PMID- 29344182
TI  - C-reactive protein/albumin and neutrophil/lymphocyte ratios and their combination
      predict overall survival in patients with gastric cancer.
AB  - Multiple studies have reported the prognostic association of certain inflammatory
      factors with various types of cancer. The present study assessed the prognostic
      value of the C-reactive protein (CRP)/albumin (Alb) ratio and the
      neutrophil/lymphocyte ratio (NLR), separately and in combination, in gastric
      cancer (GC). A total of 337 cases pathologically diagnosed with gastric
      adenocarcinoma were retrospectively evaluated. The clinicopathological and
      prognostic relevance of the CRP/Alb ratio and NLR and their combination were
      analyzed. The optimal cut-off values of the CRP/Alb ratio and NLR were 0.38 and
      3.14, respectively. High CRP/Alb ratio (>=0.38) and NLR (>=3.14) values were
      associated with increased tumor invasion, more distant metastasis and a more
      advanced tumor-node-metastasis stage (all P<0.05). In addition, a high NLR value
      was also associated with increased tumor size (P=0.02). The CRP/Alb ratio
      (>=0.38/<0.38) and NLR (>=3.14/<3.14) were independent prognostic factors for
      overall survival time (OS) in GC by multivariate analysis (P=0.005 and P=0.001).
      Using the CRP/Alb ratio and NLR classification, patients were stratified into
      three subgroups with different OS time (P<0.001), which were identified as
      independent prognostic variables in multivariate analysis (P<0.001). The present
      study demonstrated that the CRP/Alb ratio and NLR were independent prognostic
      factors for OS in patients with GC. The combination of these indexes was
      associated with significant prognostic value and may further stratify prognosis.

PMID- 29344183
TI  - A patient with chronic myeloid leukemia and situs inversus totalis: A case
      report.
AB  - In the present study, a case of chronic myeloid leukemia (CML) with complete
      situs inversus in a 68-year-old female patient was reported. The patient
      presented with general weakness, abdominal distension and tenderness in the right
      hypochondrium. A chest X-ray revealed a right-sided heart. Ultrasonography
      revealed situs inversus totalis. A bone marrow smear demonstrated CML in the
      accelerated phase. Imatinib mesylate was subsequently administered; the patient
      stopped taking imatinib mesylate following discharge from the hospital. The
      patient presented with dizziness, fatigue, and abdominal distention and pain 1
      year subsequently. A bone marrow smear demonstrated CML in the blast crisis
      phase; CML had progressed to acute myeloid leukemia (AML) M2a. The patient was
      treated with imatinib mesylate and cytarabine. After 5 days, the white blood cell
      count had decreased compared with that measured at the time of admission, and the
      previous relevant symptoms had disappeared. The patient succumbed to AML 3 months
      after discharge from the hospital. Situs inversus totalis is an uncommon
      congenital anomaly that often occurs concomitantly with other disorders. The
      present study documented, to the best of our knowledge, the second recorded case
      of CML in a patient with situs inversus totalis. Previous studies on the
      pathogenesis of situs inversus have suggested it is caused by embryonic cells
      failing to rotate normally during early embryonic development. Although there are
      case reports of situs inversus totalis in patients with cancer, there are few
      reports on the association between situs inversus totalis and cancer. The present
      study examined a case of CML with situs inversus totalis and assessed whether the
      latter may be associated with cancer.

PMID- 29344184
TI  - Therapeutic effects of adenovirus-mediated CD and NIS expression combined with
      Na131I/5-FC on human thyroid cancer.
AB  - Thyroid cancer is the most common type of malignant endocrine tumor diagnosed.
      Previous studies have indicated that gene therapy is the most promising and
      effective therapeutic method for thyroid cancer. Therefore, in the present study,
      Na131I/5-fluorocytosine (5-FC) treatment was combined with cytosine deaminase
      (CD, encoded by the CDA gene) and sodium iodide symporter (NIS, encoded by the
      SLC5A5 gene) to act together as a therapeutic tool for thyroid cancer. The
      present study explored the combined cytotoxic effects of adenovirus-mediated CD
      and NIS under the control of the progression elevated gene-3 (PEG-3) promoter (Ad
      PEG-3-CD-NIS) with Na131I/5-FC against the human thyroid cancer TT cell line in
      vitro. The PEG-3 fragment was obtained by polymerase chain reaction (PCR) using
      rat genomic DNA as the template, and then Ad-PEG-3-CDA-SLC5A5 was constructed
      using XbaI. TT cells were transfected by recombinant adenovirus. The method of
      reverse transcription-quantitative PCR was performed to test the expression of CD
      and NIS at the level of transcription. The morphological change was assessed by
      fluorescence microscopy and investigated by western blot analysis. An MTT assay
      was used to determine the number of living cells inhibited by single or
      combination therapies on TT cells. The results indicated that the PEG-3 was
      successfully cloned, and was also positively regulated in 293 cells. CDA and
      SLC5A5 genes were highly expressed in TT cells. Na131I combined with 5-FC
      significantly decreased the human thyroid cancer cells. In conclusion,
      combination therapy of Ad-PEG3-CDA-SLC5A5 and Na131I/5-FC induces significantly
      more apoptotic characteristics than either single treatment with Ad-PEG-3-CDA
      SLC5A5 or Na131I/5-FC, and low doses of Ad-PEG-3-CDA-SLC5A5 enhanced the
      cytotoxic effects.

PMID- 29344185
TI  - Downregulation of miR-30a is associated with proliferation and invasion via
      targeting MEF2D in cervical cancer.
AB  - Accumulating studies have revealed that microRNAs serve crucial roles in cancer
      development and progression. MicroRNA-30a (miR-30a) has been implicated in
      various cancer types. However, the role of miR-30a in cervical cancer remains
      unclear. In the current study, a reverse transcription-quantitative polymerase
      chain reaction (RT-qPCR) assay revealed that miR-30a was significantly
      downregulated in cervical cancer tissues compared with adjacent normal tissues,
      and in the cervical cancer cell lines HeLa, SiHa and Ca-Ski compared with GH329
      normal cervical epithelial cells. A functional assay using miR-30a mimic
      demonstrated that miR-30a could inhibit the growth and invasion of cervical
      cancer cells. Additionally, bioinformatics-based prediction and luciferase
      reporter assays indicated that MEF2D is a direct target of miR-30a. Transfection
      with miR-30a reduced the mRNA expression and protein levels of MEF2D, as
      determined using RT-qPCR and western blot analyses. Furthermore, MEF2D expression
      was negatively correlated with that of miR-30a in cervical cancers. Overall, the
      present study demonstrated that miR-30a functions as a tumor suppressor by
      targeting MEF2D in cervical cancer, which may provide the basis for a prognostic
      biomarker or therapeutic strategy for cervical cancer.

PMID- 29344186
TI  - Downregulation of klotho beta is associated with invasive ductal carcinoma
      progression.
AB  - Klotho beta (KLB) is a single-pass transmembrane protein measuring 1,043 amino
      acids in length that shares 41.2% homology with klotho alpha (KLA). KLB is a co
      receptor and key regulator of the fibroblast growth factor receptor 4 (FGFR4)
      pathway. KLB interacts with FGFR4 to induce apoptosis and inhibit the
      proliferation of hepatoma cells, and KLA has been demonstrated to be a tumor
      suppressor in human breast cancer; however, little is known regarding the role of
      KLB in breast cancer. In the present study, through an immunohistochemical
      analysis of invasive ductal carcinoma tissue arrays, low KLB expression was
      identified in invasive ductal carcinoma samples compared with paired adjacent non
      tumorous breast tissues (82 cases). In invasive ductal carcinoma tissues, KLB
      expression was negatively associated with pathological grade and lymph node
      metastasis. In 42 cases of paired microdissected breast specimens, the condition
      of the KLB gene allele was examined to determine the loss of heterozygosity
      (LOH), and selective LOH was identified at the KLB locus in 57.1% of primary
      tumors. These data suggest that KLB may be associated with the progression and
      metastasis of invasive ductal carcinoma, and therefore have clinical and
      therapeutic importance.

PMID- 29344187
TI  - Patuletin induces apoptosis of human breast cancer SK-BR-3 cell line via
      inhibiting fatty acid synthase gene expression and activity.
AB  - Fatty acid synthase (FASN) is a key enzyme involved in fatty acid biosynthesis
      and serves an important role in breast cancer development. The aim of the present
      study was to investigate the effects of patuletin on the gene expression and
      activity of FASN in the human breast cancer SK-BR-3 cell line, and the apoptotic
      effects of patuletin to breast cancer cells. Quantitative reverse transcription
      polymerase chain reaction, western blotting and intracellular FASN activity
      assays were used to evaluate FASN gene expression, protein expression and
      activity in patuletin-treated SK-BR-3 cells. MTT assays and flow cytometry were
      used to measure cell growth and cell apoptosis, respectively, following patuletin
      treatment. As a result, it was demonstrated that patuletin dose-dependently
      reduces FASN expression and intracellular activity in human breast cancer cells,
      and induces apoptosis in FASN over-expressing SK-BR-3 cells. Notably, apoptosis
      is associated with the reduction of intracellular FASN activity. The present
      study demonstrates that patuletin may be considered as a novel natural inhibitor
      of FASN, may induce anti-proliferative and pro-apoptotic effects in certain human
      breast cancer cells and may be useful for preventing and/or treating human breast
      cancer.

PMID- 29344188
TI  - High expression of special AT-rich sequence binding protein-1 predicts esophageal
      squamous cell carcinoma relapse and poor prognosis.
AB  - Previous studies of the roles of special AT-rich sequence binding protein-1
      (SATB1) in the development and progression of cancer have suggested that SATB1
      promotes cancer cell metastasis. The aim of the present study is to evaluate the
      role of SATB1 in the progression and prognosis of esophageal squamous cell
      carcinoma (ESCC). ESCC tissues were collected from 102 patients and SATB1 mRNA
      expression was measured by reverse transcription-quantitative polymerase chain
      reaction. The association between expression of SATB1 mRNA with
      clinicopathological features and prognosis was assessed, and the prognosis of
      ESCC was evaluated using Kaplan-Meier survival curves. In the 102 ESCC tissues,
      SATB1 mRNA expression correlated with the clinical tumor node metastasis stage
      (P<0.05), but not with any other clinicopathological features (including age,
      gender, tumor differentiation grade, adjuvant radio/chemotherapy, or the
      consumption of alcohol and use of cigarettes) (P>0.05). The disease-free survival
      (DFS) and overall survival (OS) of patients with high SATB1 expression was
      decreased compared with those with low SATB1 expression. The present study
      indicated that SATB1 mRNA expression was associated with the postoperative
      recurrent and poor prognosis in ESCC. SATB1 may be a novel marker for predicting
      the recurrent and worse prognosis of ESCC.

PMID- 29344189
TI  - Phosphorylated AKT expression in tumor-adjacent normal tissue is associated with
      poor prognosis in patients with hepatocellular carcinoma.
AB  - The AKT pathway serves important roles in tumor cell growth. Its overexpression
      is associated with poor prognosis in a number of types of cancer; however, the
      role of AKT in the role of the pathogenesis of hepatocellular carcinoma (HCC)
      remains unclear. The present study was undertaken to explore the clinical
      relevance of phosphorylated AKT (p-AKT) in HCC. The level of p-AKT in tumor (TU)
      and paired adjacent normal liver (AN) tissue from 202 HCC patients was evaluated
      with immunohistochemistry. The results demonstrated that p-AKT was more highly
      expressed in TU than in AN tissue. Kaplan-Meier curves and Cox regression
      revealed that patients with a high expression of p-AKT (AN) exhibited reduced
      overall and relapse-free survival times; this was not observed at a statistically
      significant level in p-AKT (TU). Additionally, the high expression of p-AKT (AN)
      was positively correlated with hepatitis C virus (HCV) infection in HCC patients.
      These results support the hypothesis that AKT activation is a mechanism of HCV
      induced hepatocarcinogenesis, suggesting that AKT can be a therapeutic target for
      the treatment of recurrent HCC subsequent to surgical resection.

PMID- 29344190
TI  - Anticancer effect of triterpenes from Ganoderma lucidum in human prostate cancer
      cells.
AB  - Ganoderma lucidum, within the Polyporaceae family of Basidiomycota, is a popular
      traditional remedy medicine used in Asia to promote health and longevity.
      Compounds extracted from G. lucidum have revealed anticancer, antioxidant and
      liver protective effects. G. lucidum has been associated with prostate cancer
      cells. G. lucidum extracts contain numerous bioactive components; however, the
      exact functional monomer is unknown and the role of triterpenes from G. lucidum
      (GLT) in prostate cancer remain obscure. The present study investigated the
      effects of GLT on cell viability, migration, invasion and apoptosis in DU-145
      human prostate cancer cells. The results demonstrated that a high dose (2 mg/ml)
      of GLT inhibits cell viability in a dose- and time-dependent manner by the
      regulation of matrix metalloproteases. Furthermore, GLT induced apoptosis of DU
      145 cells. In general, GLT exerts its effect on cancer cells via numerous
      mechanisms and may have potential therapeutic use for the prevention and
      treatment of cancer.

PMID- 29344191
TI  - Expression and prognostic significance of cyclin-dependent kinase inhibitor 1A in
      patients with resected gastric adenocarcinoma.
AB  - Cyclin-dependent kinase inhibitor 1A (CDKN1A) is an important cell
      cycleregulator, and has been identified to exhibit aberrant expression in various
      types of cancer tissues. However, the association between CDKN1A expression level
      and prognosis in patients with resected gastric adenocarcinoma (RGA) requires
      additional elucidation. In the present study, the CDKN1A expression profile in
      RGA tissues obtained from 217 patients were analyzed using immunohistochemistry.
      Its prognostic significance was evaluated by using the chi2 test, Kaplan-Meier
      curves and the log-rank test, and a multivariate Cox model analysis, during a
      median follow-up time of 51 months. The results demonstrated that CDKN1A
      expression was significantly correlated with lymph node metastasis (LNM;
      P=0.001), recurrence (P<0.001) and overall survival (OS; P<0.001). In addition,
      the recurrence-free survival (RFS) and OS times were significantly shorter in
      patients with low CDKN1A expression compared with those with high CDKN1A
      expression (RFS, 20 months vs. 69 months, P<0.001; and OS, 32 months vs. 70
      months, P<0.001, respectively). Multivariate analysis additionally confirmed that
      low CDKN1A expression was significantly correlated with an increased risk of LNM
      (P=0.001), recurrence (P<0.001) and mortality (P<0.001). Therefore, these data
      suggest that low expression of CDKN1A has independent prognostic significance
      indicative of tumor progression and poor survival in patients with RGA.
      Evaluation of CDKN1A expression may assist in determining prognosis in patients
      with RGA.

PMID- 29344192
TI  - TSLP promotes angiogenesis of human umbilical vein endothelial cells by
      strengthening the crosstalk between cervical cancer cells and eosinophils.
AB  - Our previous study demonstrated that thymic stromal lymphopoietin (TSLP) secreted
      by cervical cancer cells promotes angiogenesis and recruitment, and regulates the
      function of eosinophils (EOS). However, the function of TSLP in the crosstalk
      between EOS and vascular endothelial cells in cancer lesions remains unknown. The
      aim of the present study was to investigate the effect of EOS caused by TSLP in
      in vitro angiogenesis of human umbilical vein endothelial cells (HUVECs). The
      results of the present study revealed that recombinant human TSLP protein
      (rhTSLP) increased the secretion of vascular endothelial growth factor (VEGF),
      but not fibroblast growth factors, in HL-60-eosinophils (HL-60E). Compared with
      cervical cancer cells (HeLa or CasKi cells) or HL-60E alone, there were increased
      levels of interleukin (IL)-8 and VEGF in the co-culture system between cervical
      cancer cells, and HL-60E cells. This effect was strengthened by rhTSLP, but
      inhibited by inhibiting the TSLP signal with anti-human TSLP or TSLP receptor
      neutralizing antibodies. The results of the tube formation assays revealed that
      treatment with the supernatant from cervical cancer cells and/or HL-60E resulted
      in an increase in angiogenesis in HUVECs, which could be decreased by TSLP or
      TSLPR inhibitors. The results of the present study suggested that TSLP derived of
      cervical cancer cells may indirectly stimulate angiogenesis of HUVECs, by
      upregulating IL-8 and VEGF production, in a co-culture model between cervical
      cancer cells and EOS, therefore promoting the development of cervical cancer.

PMID- 29344193
TI  - Identification of differentially expressed molecular functions associated with
      breast cancer using Gibbs sampling.
AB  - The aim of the present study was to identify differentially expressed molecular
      functions (DEMFs) for breast cancer using the Gibbs sampling approach. Molecular
      functions (MFs) were obtained on the basis of the Bayesian Approach for Geneset
      Selection package. Subsequently, MFs were converted into Markov chains (MCs)
      prior to calculating their probabilities, utilizing the MC Monte Carlo algorithm.
      DEMFs were identified with probabilities >=0.8 and the gene compositions were
      studied. Finally, a co-expression network was constructed via the empirical Bayes
      method and a pathway enrichment analysis of genes in DEMFs was performed. A total
      of 396 MFs were identified and all transformed to MCs. With the threshold, 2
      DEMFs (structural molecule activity and protein heterodimerization activity) were
      obtained. The DEMFs were comprised of 297 genes, 259 of which were mapped to the
      co-expression network. These 297 genes were identified to be enriched in 10
      pathways, and ribosome was the most significant pathway. The results of the
      present study revealed 2 DEMFs (structural molecule activity and protein
      heterodimerization activity) which may be associated with the pathological
      molecular mechanisms underlying breast cancer, based on Gibbs sampling.

PMID- 29344194
TI  - Chronic myeloid leukemia following repeated diagnostic X-ray exposure for the
      treatment of recurrent spontaneous pneumothorax in a patient with ankylosing
      spondylitis: A case report and literature review.
AB  - Previous studies have indicated that X-ray irradiation may increase the risk of
      chronic myeloid leukemia (CML), and the incidence of spontaneous pneumothorax in
      patients with ankylosing spondylitis (AS) is higher than in the general
      population. Patients with AS usually develop spontaneous pneumothorax several
      years after the diagnosis of AS. The present study reports the unusual case and
      complicated clinical history of a 29-year-old man with recurrent pneumothorax and
      AS, who developed CML following repeated exposure to low doses of radiation via
      diagnostic X-rays and chest computed tomography imaging. Pneumothorax was
      diagnosed prior to AS in this patient; the present case report highlights the
      importance of recognizing AS as a possible underlying cause of recurrent
      spontaneous pneumothorax. Patients with AS may be more sensitive to injury via X
      ray-derived radiation, and even small diagnostic doses may be associated with
      CML. Diagnostic X-ray exposure should therefore be limited to reduce the risk of
      radiation-associated malignancies, including CML, particularly in patients with
      AS.

PMID- 29344195
TI  - Collagen triple helix repeat containing 1 promotes tumor angiogenesis in
      gastrointestinal stromal tumors.
AB  - Collagen triple helix repeat containing 1 (Cthrc1) is a secreted protein that has
      been observed to lead to poorer prognosis by inducing the invasion and metastasis
      in different tumors; however, it has not been demonstrated that Cthrc1 is
      involved in tumor angiogenesis. Immunohistochemical staining of Cthrc1 and CD31
      in gastrointestinal stromal tumor tissue demonstrated that Cthrc1 is associated
      with microvascular density. Overexpression of Cthrc1 protein may alter the
      properties of human umbilical vein endothelial cells (HUVECs), including
      migration, invasion, tubule formation and aortic ring sprouting. Small
      interfering RNA-mediated knockdown of Cthrc1 was performed to verify the opposite
      effects. Migration and tubule formation induced by Cthrc1 overexpression in
      HUVECs was attenuated by inhibition of phosphorylation in extracellular-signal
      regulated protein kinase (ERK) and c-Jun N-terminal kinase (JNK) signaling
      pathways. The pro-angiogenic effect of Cthcr1 is associated with increased
      phosphorylation of ERK and JNK in HUVECs. Silencing the expression of Cthrc1
      protein may be a promising strategy to inhibit tumor angiogenesis.

PMID- 29344196
TI  - Downregulated expression of TSHR is associated with distant metastasis in thyroid
      cancer.
AB  - In differentiated thyroid cancer (DTC), the association between thyroid
      stimulating hormone receptor (TSHR) and metastasis, and the underlying molecular
      mechanisms remain unclear. The role of TSHR in the epithelial-mesenchymal
      transition (EMT) has not yet been reported, to the best of our knowledge. In the
      present study, the role of TSHR in the distant metastasis of DTC was
      investigated. TSHR was significantly downregulated in well-differentiated thyroid
      cancer cells and tissues, and a lack of TSHR promoted thyroid cancer cell
      invasion and metastasis by inhibiting the EMT of thyroid cancer cells. In
      addition, the prognostic value of TSHR in thyroid cancer was analyzed.
      Immunohistochemical analysis of 172 DTC tissues revealed that a lack of
      expression of TSHR was associated with distant metastasis and a poor survival
      rate. Multivariate analyses demonstrated that TSHR expression was a significant
      prognostic factor for distant metastasis and survival time. The results from the
      present study demonstrated that TSHR inhibits metastasis through regulating EMT
      in vitro, and that a lack of expression of TSHR is a significant independent
      factor affecting distant metastasis and poor prognosis in DTC.

PMID- 29344197
TI  - Overexpression of CXCR4 promotes invasion and migration of non-small cell lung
      cancer via EGFR and MMP-9.
AB  - The aim of the present study was to verify whether overexpression of CXC receptor
      4 (CXCR4) promotes the invasion and migration of non-small cell lung cancer
      (NSCLC) via epidermal growth factor receptor (EGFR) and matrix metallopeptidase-9
      (MMP-9), and to detect the association between CXCR4, EGFR and MMP-9. The effects
      of overexpression of CXCR4 on lung cancer cell functions were investigated by
      migration and invasion assays. Western blotting and zymograph assays were used to
      analyze the protein expression levels of EGFR and the production of MMP-9,
      respectively. Immunohistochemistry was applied to analyze the expression of EGFR,
      CXCR4 and MMP-9 in NSCLC. Statistical analyses were used to detect the
      associations among EGFR, CXCR4 and MMP-9 in NSCLC. Finally, survival analyses
      were performed. CXCR4 overexpression enhanced cell motility and invasion. CXCR4
      also promoted expression of EGFR and elevated MMP-9 production. CXCR4, EGFR and
      MMP-9 were highly expressed in NSCLC, and were not identified as associated with
      age and sex (P>0.05). However, they were associated with tumor differentiation
      and lymph node metastasis (P<0.05). CXCR4, EGFR and CXCR4 expression were
      positively associated with one another in NSCLC (P<0.05). In addition, patients
      with positive expression of CXCR4, EGFR or MMP-9 in tumors exhibited
      significantly shorter overall survival compared with those with negative
      expression (P<0.05). In conclusion, CXCR4 overexpression enhanced cell motility
      and invasion via EGFR and MMP-9. CXCR4, EGFR and MMP-9 were identified as highly
      expressed in NSCLC, and there was positive correlation among them.

PMID- 29344198
TI  - Combination of cecropinXJ and LY294002 induces synergistic cytotoxicity, and
      apoptosis in human gastric cancer cells via inhibition of the PI3K/Akt signaling
      pathway.
AB  - The aim of the present study was to investigate the cytotoxic and apoptotic
      effects of cecropinXJ against human gastric cancer BGC823 cells, either alone, or
      in combination with a specific phosphatidylinositol 3-kinase (PI3K) inhibitor,
      LY294002. Cell viability and the apoptosis rate were measured using flow
      cytometry with Annexin-V staining. Additionally, the expression levels of several
      RAC-alpha serine/threonine kinase (Akt) phosphorylation-associated proteins and
      apoptosis-regulating proteins were evaluated by western blot analysis. It was
      observed that the combination of cecropinXJ and LY294002 resulted in significant
      synergistic cytotoxic and apoptosis effects, as compared with any single agent
      alone, in a dose-dependent manner. Corresponding to enhanced apoptosis, the
      expression levels of certain apoptosis-regulating proteins were changed, the most
      notable being the upregulation of caspase-3, B-cell lymphoma-2 (Bcl-2)-associated
      death promotor, Bcl-2 homologous antagonist killer, Bcl-2 interacting killer, Bcl
      2-like protein 11, Bcl-2-like protein 4 and cytochrome c, and the downregulation
      of phosphorylated-Bad and Bcl-2 proteins. The present study provided a novel
      therapeutic regimen for the use of the cecropinXJ in combination with LY294002
      for the treatment of gastric cancer.

PMID- 29344199
TI  - Expression and prognostic significance of doublecortin-like kinase 1 in patients
      with hepatocellular carcinoma.
AB  - Doublecortin-like kinase 1 (DCLK1), a putative cancer stem cell marker in
      intestinal and pancreatic tumors, is associated with tumor pathogenesis and
      progression, and poor survival outcomes in numerous types of cancer. However,
      DCLK1 expression and its prognostic value remain unclear in hepatocellular
      carcinoma (HCC). In the present study, the expression of DCLK1 was assessed using
      immunohistochemistry in 96 resected HCC and 68 adjacent tissue specimens. The
      staining intensity and the percentage of stained cells were scored on a scale of
      0-3 and 0-4, respectively. Tissue was defined as positive for DCLK1 if the
      composite multiple score was >3. Cytoplasmic expression of DCLK1 was observed in
      HCC and adjacent tissue specimens with an expression rate of 81% (78/96) and 74%
      (50/68), respectively; the median score was 4.6 and 3.9, respectively, and no
      statistically significant difference was observed between HCC and adjacent
      tissues (P=0.087). DCLK1 expression was positively associated with intrahepatic
      metastasis (P=0.035). Furthermore, univariate analysis revealed that DCLK1
      expression was significantly associated with poor disease-free survival (DFS) and
      overall survival (P=0.024 and 0.034). Multivariate analysis also demonstrated
      that DCLK1 expression was an independent prognostic factor for DFS in HCC
      (P=0.019; hazard ratio, 1.546; 95% confidence interval, 1.330-1.725). Stratified
      Kaplan-Meier survival curves revealed that DCLK1 expression predicted poorer DFS
      with respect to positivity for three characteristics: Portal venous metastasis,
      intrahepatic metastasis, and cirrhosis (P=0.020, P=0.007 and P=0.017,
      respectively). Collectively, the results of the present study suggested that
      DCLK1, functioning as a tumor promoter, is frequently overexpressed in HCC, and
      that DCLK1 expression is associated with poor DFS in patients with HCC. DCLK1 may
      represent a promising therapeutic target in HCC and requires further study.

PMID- 29344200
TI  - Molecular pathological predictive diagnostics in a patient with non-small cell
      lung cancer treated with crizotinib therapy: A case report.
AB  - Lung cancer is one of the most common malignant cancers in the Czech Republic in
      men, with the highest mortality rate of all the malignant diseases. The
      development of biological treatment enables study into novel personalized
      treatment options. This type of treatment is usually of high quality, and is
      often demanding of predictive and biopsy diagnostics, which is dependent on the
      quality of the collected material and close cooperation among particular
      departments. The present study describes the complete biopsy and predictive
      examinations performed in a male patient with lung adenocarcinoma, with an
      emphasis on the logistics of the whole process and the application of the
      tyrosine kinase inhibitors, crizotinib and LDK378. The patient experienced a long
      overall survival time of 28 months from diagnosis.

PMID- 29344201
TI  - Elevation of serum CEA and CA15-3 levels during antitumor therapy predicts poor
      therapeutic response in advanced breast cancer patients.
AB  - The aim of the present study was to assess the correlation between therapeutic
      response and carcinoembryonic antigen (CEA) and carbohydrate antigen 15-3 (CA15
      3) levels in advanced breast cancer patients with non-assessable lesions or
      stable disease (SD) according to the Response Evaluation Criteria in Solid
      Tumors. A total of 232 female patients with recurrent tumors following radical
      mastectomy were recruited, including 76 patients with non-assessable lesions and
      60 patients with SD. The correlation between CEA and CA15-3 changes, progression
      free survival (PFS) and therapeutic response were analyzed in the non-assessable
      and SD patient groups. For all subjects, the association between the patients'
      serum tumor markers levels and the clinical presentation of the tumor, as well as
      the correlation between initial tumor marker levels and PFS, were analyzed. An
      increase in CEA (an increment of >2 ng/ml) or CA15-3 levels (an increase of >15
      U/ml) following the second cycle of treatment correlated with shorter PFS in both
      non-assessable and SD patients, and with poor clinical outcome in SD patients.
      High CA15-3 levels correlated with hormone receptor-positive tumors, multiple
      metastases and liver metastases. Bone metastases correlated with high levels of
      both CEA and CA15-3. Relatively low CEA and CA15-3 concentrations were associated
      with triple-negative and locally invasive tumors. High CEA and CA15-3 levels at
      the beginning of relapse correlated with shorter PFS. The present study
      illustrates that CEA and CA15-3 levels correlate with several factors in
      recurrent breast cancer patients. Elevated levels of CEA and CA15-3 at the
      beginning of relapse may predict shorter PFS. Furthermore, elevation of CEA and
      CA15-3 levels following the second therapeutic cycle predict poor therapeutic
      response in patients with non-assessable lesions and SD. Our findings suggest
      that alterations in CEA and CA15-3 levels can predict therapeutic response in
      advanced breast cancer patients.

PMID- 29344202
TI  - Metformin in combination with cisplatin inhibits cell viability and induces
      apoptosis of human ovarian cancer cells by inactivating ERK 1/2.
AB  - Metformin protects against insulin resistance by restoring insulin sensitivity
      and may also possess anticancer activity. The aim of the present study was to
      investigate the effects of metformin alone or combined with cisplatin (DDP) on
      the cell viability and apoptosis of HO-8910 human ovarian cancer cells, and to
      investigate metformin as a potential novel therapeutic for treating ovarian
      cancer. The viability of HO-8910 cells was assessed using a cell proliferation
      and cytotoxicity assay following treatment with different concentrations of
      metformin (0.01, 0.5, 1, 5 and 10 mM) and/or 5 uM of DDP. Flow cytometry was
      performed to examine cell apoptosis, and western blotting was used to measure the
      expression of extracellular signal-related kinase 1/2 (ERK1/2) phosphorylated (p)
      ERK1/2, vascular endothelial growth factor (VEGF), VEGF receptor 2 (VEGFR2), B
      cell lymphoma 2 (Bcl-2), Bcl-2-associated X (Bax) and caspase-3. The resultsof
      the present study revealed that metformin reduced the viability of HO-8910 cells
      in a time- and concentration-dependent manner and induced cell apoptosis in a
      concentration-dependent manner. Metformin combined with DDP evidently inhibited
      cell viability and induced apoptosis. In addition, ERK1/2 and genes associated
      with apoptosis regulation, such as VEGF, VEGFR2, Bcl-2, Bax and caspase-3,
      exhibited differential expression in the HO-8910 cells. The present study
      demonstrated that expression of p-ERK1/2, VEGF, VEGFR2 and Bcl-2 was
      downregulated by treatment with increasing concentrations of metformin, whereas
      expression of Bax and caspase-3 was evidently upregulated. Taken together, these
      data demonstrate that metformin in combination with DDP reduces cell viability
      and induces apoptosis of human ovarian cancer cells.

PMID- 29344203
TI  - Mucin 1 promotes radioresistance in hepatocellular carcinoma cells through
      activation of JAK2/STAT3 signaling.
AB  - Mucin 1 (MUC1) is aberrantly overexpressed in numerous human cancer types,
      including hepatocellular carcinoma (HCC) and contributes to chemoresistance of
      tumor cells. The aim of the present study was to evaluate the possible
      implication of MUC1 in radioresistance of HCC cells and the underlying
      mechanisms. It was demonstrated that MUC1 was significantly upregulated in HCC
      cells following irradiation exposure, which was coupled with increased
      phosphorylation of signal transducer and activator of transcription 3 (STAT3).
      Enforced expression of MUC1 significantly (P<0.05) promoted the clonogenic
      survival of HCC cells following irradiation compared with empty vector
      transfected cells. MUC1 overexpression resulted in >60% reduction in apoptosis
      induced by irradiation, as determined by Annexin-V/propidium iodide double
      staining and flow cytometry analysis. Furthermore, overexpression of MUC1
      significantly (P<0.05) attenuated the activation of caspase-3 and poly (ADP
      ribose) polymerase in response to irradiation exposure. Mechanistically, MUC1
      inhibited irradiation-induced apoptosis through activation of janus kinase 2
      (JAK2) and STAT3, and induction of anti-apoptotic proteins induced myeloid
      leukemia cell differentiation protein Mcl-1 (Mcl-1) and BCL2 like 1 (Bcl-xL).
      Small hairpin RNA-mediated knockdown of STAT3 or MUC1 resensitized MUC1
      overexpressing cells to irradiation-induced apoptosis, which was accompanied by
      reduced expression of Bcl-xL and Mcl-1. Collectively, MUC1 contributes to
      radioresistance of HCC cells likely through activation of the JAK2/STAT3
      signaling pathway and thus represents a potential target for improving
      radiotherapy against HCC.

PMID- 29344204
TI  - Silibinin inhibits the migration and invasion of human gastric cancer SGC7901
      cells by downregulating MMP-2 and MMP-9 expression via the p38MAPK signaling
      pathway.
AB  - The objective of the present study was to observe the effects of silibinin and
      the p38 mitogen-activated protein kinase (MAPK) signaling pathway inhibitor
      SB203580 on the migration and invasion capabilities of SGC7901 cells, and to
      explore the underlying associated mechanisms. Scratch, Transwell and Matrigel
      invasion assays were performed to study the effects of silibinin on cell
      migration and invasion. Western blot analysis was used to determine the
      expression levels of p38MAPK, phosphorylated (p-)p38MAPK, matrix
      metalloproteinase (MMP)-2 and MMP-9. At the genomic level, quantitative
      polymerase chain reaction was performed to evaluate the expression levels of MMP
      2 and MMP-9. The results of scratch assay indicated that silibinin inhibited the
      migration capabilities of human gastric cancer SGC7901 cells in a dose-dependent
      manner. Additionally, Matrigel invasion and Transwell migration assays revealed
      that silibinin and SB203580 combined treatment significantly reduced the number
      of invasive cells. Western blot analysis indicated a reduced phosphorylation of
      p38MAPK without marked changes in p38MAPK expression. In addition, the expression
      of MMP-2 and MMP-9 significantly decreased in the presence of silibinin,
      SB203580, and the combination of silibinin and SB203580. In summary, silibinin
      decreased the invasion and migration abilities of SGC7901 cells by downregulating
      the expression of MMP-2 and MMP-9 through inhibiting p38MAPK signaling cascades.

PMID- 29344205
TI  - MicroRNA-138 suppresses cell proliferation and invasion of renal cell carcinoma
      by directly targeting SOX9.
AB  - An accumulating number of studies have reported that the expression levels of
      microRNAs (miRNAs/miRs) are dysregulated in a variety of human cancer types,
      including renal cell carcinoma (RCC). miRNAs play essential functions in
      tumorigenesis and the progression of tumors by serving as oncogenes or tumor
      suppressors. Recently, the expression and functions of miR-138 have been studied
      in a number of human cancer types; however, its role in RCC remains poorly
      understood. In the present study, the results revealed that miR-138 was
      significantly downregulated in RCC cell lines and tissues, and that low
      expression levels of miR-138 were correlated with histological grade, tumor stage
      and lymph node metastasis. In functional studies, restoration of miR-138
      expression inhibited cell proliferation and invasion of ACHN and A498 cells. In
      addition, SOX9 was validated as a direct target gene of miR-138 in RCC. SOX9
      knockdown inhibited cell proliferation and invasion of RCC, with a similar effect
      to that induced by miR-138, rendering SOX9 a functional target of miR-138 in the
      disease. These findings indicate that miR-138 may present a novel target for
      therapeutic strategies in RCC.

PMID- 29344206
TI  - Impact of metastatic status on the prognosis of EGFR mutation-positive non-small
      cell lung cancer patients treated with first-generation EGFR-tyrosine kinase
      inhibitors.
AB  - The aim of the present study was to analyze the impact of metastatic status on
      the prognosis of epithelial growth factor receptor (EGFR) mutation-positive
      patients with non-small cell lung cancer (NSCLC) treated with first-generation
      EGFR-tyrosine kinase inhibitors (TKIs). A total of 178 EGFR mutation-positive
      patients with stage IIIB-IV and relapsed NSCLC who were treated with gefitinib or
      erlotinib as the first-line treatment were enrolled in the present study.
      Metastatic status, progression-free survival (PFS), overall survival (OS) and
      treatment-response rates were investigated. The association between the number of
      metastatic organ sites and patient prognosis was also investigated. The median
      age at the time of treatment was 72 (range, 39-91) years. A total of 168 patients
      had adenocarcinoma; 156 were treated with gefitinib. Patients with brain
      metastases, bone metastases, liver metastases and pleural effusion exhibited a
      significantly reduced PFS and OS time in the univariate analysis, compared with
      patients without each of these symptoms. In the multivariate analysis, bone
      metastasis was associated with a poorer PFS (hazard ratio, 2.11; 95% confidence
      interval, 1.44-3.09; P<0.001) and brain metastasis was associated with a poorer
      OS (hazard ratio, 2.41; 95% confidence interval, 1.46-3.95; P<0.001). No
      association was observed between metastatic status and treatment response rates.
      Higher numbers of different sites of organ metastases were associated with
      significantly poorer PFS and OS. Bone, brain metastasis and higher numbers of
      metastatic organ sites are negative prognostic factors for EGFR mutation-positive
      NSCLC patients treated with first-generation EGFR-TKIs.

PMID- 29344207
TI  - Novel homobarringtonie-containing therapy for the treatment of patients with
      primary acute myeloid leukemia that are resistant to conventional therapy.
AB  - The current study investigated the efficacy and safety of a novel treatment
      regime consisting of homobarringtonie, cytosine arabinoside and etoposide (HCE)
      for the treatment of primary acute myeloid leukemia (AML). In the present study,
      141 patients diagnosed with AML were divided into the HCE (n=47) and the
      conventional AML therapy, consisting of idamycin combined with cytarabine (IA;
      n=94), treatment groups. The measured patient outcome parameters were the
      emission and response rates, as well as medication-induced adverse events, with a
      median follow-up time of 28 months. There was no significant difference in the 3
      year relapse-free survival rate between the HCE and IA treatment groups. The
      occurrence and severity of hematological or non-hematological toxicity did not
      differ between the two groups. However, of the 26 patients that demonstrated a
      poor response to the IA treatment, 19 cases were administered the HCE treatment
      and 14 of these patients achieved complete remission (CR). Of the 10 patients
      that demonstrated a poor response to the HCE treatment, 8 patients were
      administered the IA treatment and 7 of these achieved CR. Therefore, HCE may be
      an effective treatment regimen for patients with primary AML. As there was no
      cross-resistance between the HCE and IA regimens, HCE may be an alternative
      option for patients that respond poorly to IA induction therapy.

PMID- 29344208
TI  - Serum levels of anti-sperm-associated antigen 9 antibody are elevated in patients
      with hepatocellular carcinoma.
AB  - At present, there is a high incidence of viral hepatitis and high mortality rates
      due to hepatocellular carcinoma (HCC) in China. In the current study, the
      quantification of antibodies against the cancer-testis antigen sperm-associated
      antigen 9 (SPAG9), alone and combined with alpha-fetoprotein (AFP), were
      evaluated as biomarkers for the diagnosis of HCC. The levels of anti-SPAG9
      antibody and AFP were quantified in serum samples from patients with HCC and
      hepatitis or cirrhosis, as well as healthy volunteers. The results revealed that
      the serum levels of anti-SPAG9 immunoglobulin G antibody in patients with HCC
      were significantly higher compared with those in patients with
      hepatitis/cirrhosis and healthy controls. Using receiver operator characteristic
      curves, the area under the curve (AUC, 0.870) of SPAG9 as a diagnostic marker of
      HCC was significant [P<0.001; 95% confidence interval (CI), 0.793-0.947], whereas
      the AUC of AFP was 0.832 (P<0.001; 95% CI, 0.736-0.928). Serum anti-SPAG9
      antibody levels exhibited significant potential for the differential diagnosis of
      HCC, with an AUC value of 0.729, (P=0.008; 95% CI, 0.559-0.899). Similarly, serum
      AFP levels exhibited significant value for the differential diagnosis of HCC,
      with an AUC value of 0.842 (P<0.001; 95% CI, 0.732-0.953). When combined with
      quantification of AFP, the diagnostic sensitivity and specificity of anti-SPAG9
      levels were increased. In summary, the results suggested that anti-SPAG9 antibody
      is a potential early diagnostic marker of HCC.

PMID- 29344209
TI  - The effect of royal jelly on the growth of breast cancer in mice.
AB  - Due to various pharmacological properties, including antioxidative, anti
      inflammatory and antibiotic properties, royal jelly (RJ) has been widely consumed
      in daily diets in numerous countries. In the present study, the effect of RJ on
      4T1-bearing mice was investigated. The study was performed by feeding 4T1-bearing
      mice with RJ using either the prophylactic-therapeutic (PTRJ) or therapeutic
      (TRJ) method. The experimental results for the PTRJ group demonstrated that the
      weight of tumor was significantly reduced (RJ 0.5 and 1.5 g/kg); and in the
      serum, the levels of interleukin (IL)-2 (RJ 0.5 and 1.5 g/kg), interferon (IFN)
      alpha, superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) were
      significantly elevated, but the concentrations of IL-4 (RJ 0.5 and 1.5 g/kg) and
      IL-10 (RJ 1.0 g/kg) were significantly decreased. In addition, the activities of
      T-AOC and glutathione reductase (GR) were significantly improved in the liver,
      whereas in the kidney, the activities of T-AOC and GR were significantly
      increased only under the dose of 0.5 g/kg. For the TRJ group, the antitumor
      effect of RJ was not significant; the change in IL-2, IFN-alpha, SOD and T-AOC
      levels in the serum, and the change in T-AOC and GR in liver were similar to
      those observed in the PTRJ groups. RJ treatment was demonstrated to reduce the
      development of breast tumor in mice, and simultaneously improve the antioxidant
      capacity of the serum, liver and kidney, particularly using the prophylactic
      therapeutic method. These results corroborated the efficacy of RJ supplementation
      in diets. The results of the present study suggest that the antioxidant and
      immunomodulatory activities of RJ serve an important role on antitumor growth.

PMID- 29344210
TI  - MicroRNA-335 is downregulated in papillary thyroid cancer and suppresses cancer
      cell growth, migration and invasion by directly targeting ZEB2.
AB  - MicroRNAs (miRs) are a group of short, endogenous, non-protein-coding and single
      stranded RNAs that regulate gene expression by binding to the 3'-untranslated
      region (3'UTR) of mRNAs, which results in their degradation or translational
      repression. The aim of the present study was to investigate the expression and
      function of miR-335 in human papillary thyroid cancer (PTC). Reverse
      transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to
      quantify the relative miR-335 expression levels in PTC tissues and cell lines.
      The effect of miR-335 on the proliferation, migration and invasion of PTC cells
      was assessed by an MTT assay, and transwell migration and invasion assays,
      respectively. Dual-luciferase reporter assays were employed to explore whether
      miR-335 directly targeted the 3'UTR of the potential target gene zinc finger E
      box binding homeobox 2 (ZEB2). RT-qPCR and western blotting were adopted to
      assess the effect of miR-335 on the mRNA and protein expression of ZEB2. RT-qPCR
      revealed that miR-335 was downregulated in PTC tissues and cell lines. The MTT
      assay and transwell migration and invasion assays demonstrated that the
      overexpression of miR-335 significantly inhibited the proliferation, migration
      and invasion of PTC cells. ZEB2 was identified as a direct target of miR-335 with
      computational analysis, which was confirmed with a dual-luciferase reporter
      assay, RT-qPCR and western blotting. The knockdown of ZEB2 significantly
      inhibited the proliferation, migration and invasion of PTC cells, indicating that
      ZEB2 may be a functional target of miR-335. Taken together, these findings
      suggested that miR-335 functioned as a tumor suppressor and suppressed the growth
      and metastatic behavior of PTC cells by targeting ZEB2.

PMID- 29344211
TI  - Prevalence of HPV infection among HIV-positive and HIV-negative women in
      Central/Eastern Italy: Strategies of prevention.
AB  - The present cross-sectional-study aimed to determine the prevalence of human
      papillomavirus (HPV)-genotypes among human immunodeficiency virus (HIV)-positive
      and -negative women in Central/Eastern Italy, and to identify the optimal
      strategies for effective HPV-prevention in each group. A representative sample of
      HIV-negative (150/200) and -positive (50/200) women, who underwent cervico
      vaginal-swabbing. Swabs were analysed for a cytological screening and for a HPV
      DNA-genotyping-test. A total of 66/200 swabs resulted HPV-positive. The overall
      HPV-prevalence was 33% with a higher prevalence in the HIV-positive-group (48%)
      compared with the HIV-negative-group (28%). The most frequent genotypes were: 16,
      31, 52, 58, 66, 73 and 89. Furthermore, the prevalence of specific genotypes was
      different in each group. The results of the present study indicate that HIV
      infection appears to be an independent risk factor for HPV-infection. In
      addition, HPV-infection is more common and more likely to persist in HIV-positive
      compared with in HIV-negative women. The optimal way to counteract HPV infection
      is through primary prevention. The stage of immunity (cluster of differentiation
      4-level) at the time of the HPV-screening is one of the most important parameters
      for detection of susceptibility to HPV-infection and to evaluate the response to
      the HPV-vaccine in HIV-positive women. It may be used to determine the sub-group
      of HIV-positive women that are more prone to HPV-infections or that exhibit a
      partial response to the HPV-vaccine. At present, a novel type of vaccine with 9
      genotypes is available and in the near future, it may serve an essential role in
      the prevention of HPV infections.

PMID- 29344212
TI  - Coexistence of sarcoidosis and metastatic lesions: A diagnostic and therapeutic
      dilemma.
AB  - Sarcoidosis, a chronic, inflammatory disease that affects various different
      organs, is characterized by noncaseating epitheloid granulomas. This systemic
      inflammatory process is associated with an increased risk of cancer. Several
      cases of sarcoidosis that mimic metastatic tumor progression in radiological
      findings have been reported so far. However, there are also cases that have
      presented a coexistence of sarcoidosis and metastasis, which have caused a
      diagnostic and therapeutic dilemma. Due to inadequate current therapies, a
      reliable differentiation between benign and malignant lesions is crucial. This
      review focuses on the residual risk of the coexistence of metastases within
      radiological suspicious lesions in patients with a history of solid tumors and
      sarcoidosis, as well as immunological findings, in order to explain the potential
      associations. Sarcoidosis has the potential to promote metastasis as it includes
      tumor-promoting and immune-regulating cell subsets. Notably, myeloid derived
      suppressor cells may serve a pivotal role in metastatic progression in patients
      with sarcoidosis. In addition, the present review also evaluates the potential
      novel diagnostic approaches, which may be able to differentiate between
      metastatic lesions and sarcoidosis. The risk of coexistent metastasis in
      sarcoidosis lesions must be considered by clinical practitioners, and a
      multidisciplinary approach may be required to avoid misdiagnosis and the
      subsequent unnecessary surgery or insufficient treatments.

PMID- 29344214
TI  - Association of the rs2071559 (T/C) polymorphism with lymphatic metastasis in
      patients with nasopharyngeal carcinoma.
AB  - Vascular endothelial growth factor (VEGF) and its receptor, VEGFR2, serve a
      critical role in angiogenesis and lymphangiogenesis, which are involved in the
      initiation and progression of malignancies. Specific single nucleotide
      polymorphisms of VEGF and VEGFR2 have been shown to modulate gene expression and
      influence malignancy aggressiveness. The aim of the present study was to
      determine whether the VEGFR2 rs2071559 (T/C) polymorphism is associated with the
      risk of developing nasopharyngeal carcinoma (NPC) and the aggressiveness of NPC
      in a southern Chinese population. A case-control study comprising 171 NPC
      patients and 184 healthy individuals was performed. Genotyping of the rs2071559
      polymorphism was performed by quantitative polymerase chain reaction using TaqMan
      probes. Genotype and allele distribution of the rs2071559 polymorphism was not
      associated with the risk of NPC following adjustment for age, sex and ethnicity
      by multivariate logistic regression analyses. Regional lymph node metastasis was
      significantly correlated with the rs2071559 C allele and the related genotypes
      (OR 0.402, 95% CI 0.193-0.835, P=0.016; and OR 0.347, 95% CI 0.145-0.829,
      P=0.024, respectively). No correlations between genotype or allele distribution
      and the primary tumor size, distant metastasis, clinical stage, or histological
      type were observed. The rs2071559 polymorphism was shown to have an association
      with lymphatic metastasis in patients with NPC; however, the precise molecular
      mechanism should be elucidated in additional studies.

PMID- 29344213
TI  - Sentinel lymph node mapping in gynecological oncology.
AB  - The intraoperative mapping of sentinel lymph nodes (SLNs) is part of the
      treatment strategy for a number of types of tumor. To retrospectively compare
      results from the mapping of pelvic SLNs for gynecological oncology, using
      distinct dyes, the present review was conducted to determine the clinical
      significance of SLN mapping for gynecological oncology. In addition, the present
      study aimed at identifying an improved choice for SLN mapping tracers in clinical
      application. Each dye exhibits demerits when applied in the clinical environment.
      The combination of radioisotopes and blue dyes was identified to exhibit the most
      accurate detection rate of SLN drainage of gynecological oncology. However,
      contrast agents were unable to identify whether a SLN is positive or negative for
      metastasis prior to pathologic examination; additional studies are required.

PMID- 29344215
TI  - miR-203a suppresses cell proliferation by targeting E2F transcription factor 3 in
      human gastric cancer.
AB  - MicroRNAs (miRs) are a class of short non-coding RNAs that serve an essential
      role in the tumorigenesis of gastric cancer (GC). MiR-203a has been reported as a
      tumor repressor in various types of human cancer. In the present study, the
      function of miR-203a on the proliferation of GC cells was investigated.
      Bioinformatics analyses revealed that miR-203a targets the 3'-untranslated region
      of E2F transcription factor 3 (E2F3) messenger RNA. A luciferase reporter assay
      and western blot analysis were performed to confirm whether E2F3 was a target of
      miR-203a. The relative luciferase activity was decreased when overexpressing miR
      203a with E2F3-wild type pmirGLO-3'-untranslated region vector, compared with the
      control group in HEK293 cells. Overexpression of miR-203a suppressed cell
      proliferation and colony formation of SGC-7901 and AGS GC cells. Inhibition of
      miR-203a promoted the proliferation of GC cells. Collectively, the results
      indicated that miR-203a may function as a tumor suppressor in GC by targeting
      E2F3.

PMID- 29344216
TI  - Hypermethylation downregulates P2X7 receptor expression in astrocytoma.
AB  - The present study investigated the altered expression of p2X purinoceptor (P2X7R)
      in astrocytoma. Reverse transcription-quantitative polymerase chain reaction and
      western blot analysis were used to determine the P2X7R expression in glioblastoma
      (GBM) and surrounding normal brain tissue. DNA methylation levels of P2X7R gene
      promoter in GBM were analyzed using a Sequenom MassARRAY(r) System.
      Immunohistochemistry (IHC) was used to detect the expression of P2X7R in
      astrocytoma at different malignancy grades, including diffuse astrocytoma,
      anaplastic astrocytoma and GBM. P2X7R mRNA and protein were significantly
      decreased in GBM compared with normal brain tissues. IHC results showed a
      negative correlation between P2X7R expression and tumor grade. The decreased
      P2X7R expression was mostly attributed to hypermethylation of its promoter.
      Therefore, P2X7R was found to perform an important role in tumorigenesis and
      progression of astrocytoma.

PMID- 29344217
TI  - Aleukemic extramedullary T lymphoid/myeloid bilineage hematopoietic and lymphoid
      malignancy with progression to bilineage leukemia at relapse: A case report.
AB  - Bilineage T lymphoid and myeloid (T/My) neoplasms are rare entities among the
      hematopoietic and lymphoid malignancies. The majority of patients present with
      leukemic symptoms in which blasts are observed in the peripheral blood (PB) or
      bone marrow (BM) at a percentage of >20% of nucleated cells. Only a minimal
      number of cases of T/My bilineage hematopoietic and lymphoid malignancy have been
      reported with extramedullary infiltration as the initial symptom. The origin of
      the neoplastic cells in T/My bilineage malignancy has been documented as the
      hematopoietic stem cells. The present study reports the case of a 31-year-old man
      with a T/My bilineage malignancy, which initially showed cervical lymph node
      enlargement beyond the diagnostic criteria of leukemia in the PB and in the BM.
      Two distinct malignant populations were detected in the cervical lymph node and
      pleural effusion, one of which was positive for MPO-staining, while the other was
      positive for cytoplasmic cluster of differentiation 3. Mutations in platelet
      derived growth factor receptor alpha, platelet-derived growth factor receptor
      beta, fibroblast growth factor receptor 1 and other chromosome abnormalities were
      excluded. The patient obtained complete remission after conventional
      chemotherapy, but relapsed with bilineage leukemia within a short period of time.
      Lymphoid and myeloid lineages have been reported to be differentiated from
      multipotent progenitors asymmetrically. However, the cellular mutation stage in
      T/My bilineage malignancy remains unclear. The present study also reviews the
      origin, development and therapeutic strategies for extramedullary T/My bilineage
      malignancy.

PMID- 29344218
TI  - ATRA increases iodine uptake and inhibits the proliferation and invasiveness of
      human anaplastic thyroid carcinoma SW1736 cells: Involvement of beta-catenin
      phosphorylation inhibition.
AB  - All-trans-retinoic acid (ATRA) can enhance iodine uptake capability of thyroid
      tumors, but the mechanisms remain poorly understood. The aim of the present study
      was to investigate the effects of ATRA on isotope susceptibility, proliferation
      and invasion of anaplastic thyroid carcinoma (ATC) and potential mechanisms.
      SW1736 cells were treated with 1 umol/l ATRA or 1% ethanol for 5 days. A cell
      line stably expressing beta-catenin-shRNA was established. An iodine uptake assay
      was performed using 125I. Proliferation and invasiveness were tested using MTT
      and Transwell assays, respectively. Western blotting was used to assess the
      expression of beta-catenin, glycogen synthase kinase-3beta (GSK-3beta),
      sodium/iodine symporter (NIS) and proteins involved in epithelial-mesenchymal
      transition. Cells pretreated with ATRA were injected subcutaneously into SCID
      mice. Mice were intraperitoneally injected with 131I once on the first day of
      treatment, and tumor growth was then assessed. After 35 days of 131I treatment,
      ATRA-pretreated tumor volume and weight were decreased compared with the 131I
      alone group (163.32+/-19.57 vs. 332.06+/-21.37 mm3; 0.35+/-0.14 vs. 0.67+/-0.23
      g, both P<0.05). Similar results were observed in the beta-catenin shRNA
      pretreated tumors. ATRA also increased the uptake of iodine by SW1736 cells
      (P<0.01), and similar results were observed in beta-catenin shRNA cells. ATRA
      treatment decreased the cell proliferation and invasion compared with control
      cells (all P<0.05), similar to beta-catenin shRNA. ATRA treatment decreased the
      expression of phosphorylated (p-)beta-catenin, p-GSK-3beta, vimentin, and
      fibronectin, and increased the expression of NIS and E-cadherin, compared with
      the control. ATRA increased the iodine uptake and inhibited the proliferation and
      invasion of SW1736 cells, involving beta-catenin phosphorylation. In conclusion,
      ATRA could be used to improve the isotope sensitivity of ATC.

PMID- 29344219
TI  - Upregulation of miR-146a increases cisplatin sensitivity of the non-small cell
      lung cancer A549 cell line by targeting JNK-2.
AB  - The aim of the present study was to investigate the effects of microRNA (miR
      )146a on the cisplatin sensitivity of the non-small cell lung cancer (NSCLC) A549
      cell line and study the underlying molecular mechanism. The differences in
      expression of miRNAs between A549 and A549/cisplatin (A549/DDP) cells were
      determined, and miR-146a was selected to study its effect on cisplatin
      sensitivity of A549/DDP cells. miR-146a mimic and inhibitor transient
      transfection systems were constructed using vectors, and A549/DDP cells were
      infected with miR-146a mimic and inhibitor to investigate growth, apoptosis and
      migration. The directed target of miR-146a was determined and the underlying
      molecular mechanism was validated in the present study. The results of the
      present study demonstrated that miR-146a was downregulated in NSCLC A549/DDP
      cells, compared with A549 cells. The overexpression of miR-146a induced apoptosis
      and inhibited the growth and invasion of A549/DDP cells, which resulted in
      increased cisplatin sensitivity in NSCLC cells. The JNK2 gene was determined as
      the direct target of miR-146a, and may be activated by the overexpression of miR
      146a. Additionally, JNK2 activated the expression of p53 and inhibited B cell
      lymphoma 2. The upregulation of miR-146a increased cisplatin sensitivity of the
      A549 cell line by targeting JNK2, which may provide a novel method for treating
      NSCLC cisplatin resistance.

PMID- 29344220
TI  - Overexpression of microRNA-1470 promotes proliferation and migration, and
      inhibits senescence of esophageal squamous carcinoma cells.
AB  - MicroRNA-1470 (miR-1470) is overexpressed in esophageal squamous cell carcinoma
      (ESCC); however, its role and underlying molecular mechanism remain unknown. The
      aim of the present study was to explore the tumorigenic role and mechanism of miR
      1470 overexpression in ESCC. The expression of miR-1470 in ESCC tissues and cell
      lines was detected using human miRNA microarrays and the reverse transcription
      quantitative polymerase chain reaction, respectively. The effects of miR-1470 on
      cell proliferation, migration and senescence were determined using a Cell
      Counting Kit-8 assay, Transwell migration assay and beta-galactosidase staining
      kit. Western blotting was used to analyze the expression levels of genes in the
      apoptosis signaling pathway. An increased expression level of miR-1470 was
      observed in ESCC tissues compared with that in paracancerous tissues. Knockdown
      of miR-1470 significantly suppressed proliferation, and down-regulated the cell
      cycle regulatory gene cyclin E1. It was also revealed that knockdown of miR-1470
      significantly inhibited migration, and decreased the expression levels of matrix
      metalloproteinase 2 (MMP2), MMP13 and MMP14. Western blotting analysis revealed
      that knockdown of miR-1470 induced apoptosis by increasing B-cell lymphoma 2 (Bcl
      2) expression. The results of the present study suggest that overexpression of
      miR-1470 in ESCC promotes cancer cell proliferation by accelerating the cell
      cycle and inhibiting apoptosis, and also enhances cancer cell migration by
      upregulating MMPs.

PMID- 29344221
TI  - Livin serves as a prognostic marker for mid-distal rectal cancer and a target of
      mid-distal rectal cancer treatment.
AB  - Livin is a novel member of the inhibitor of apoptosis protein family, which has
      been identified to be expressed in various malignancies and is suggested to be
      associated with poor prognostic significance. However, no data are available
      concerning the significance of livin in mid-distal rectal cancer. In the present
      study, livin expression, and its association with clinicopathological
      characteristics and prognosis was examined in patients with mid-distal rectal
      cancer. Apoptotic susceptibility, invasion capacity and chemosensitivity of LoVo
      cells were investigated using small interfering RNA (siRNA)-mediated knockdown of
      livin. It was revealed that livin was highly expressed in mid-distal rectal
      cancer tissues compared with the normal rectal mucosal tissues. Livin expression
      was associated with pathological grade, extent of invasion (T stage) and extent
      of lymph node metastasis (N stage) of tumor, contributing to poor prognosis of
      mid-distal rectal cancer following surgery. The data suggest that aggressive
      surgery should be applied in patients with mid-distal rectal cancer with high
      expression of livin. It was also revealed that knockdown of livin by siRNA
      increased the apoptotic rate, suppressed invasion of LoVo cells, and decreased
      the half-maximal inhibitory concentration of oxaliplatin and 5-fluorouracil by
      ~50% in LoVo cells significantly compared with control groups. The data suggested
      that a combination of downregulation of livin and anticancer drugs may
      significantly decrease the toxicity of anticancer drugs. Taken together, the
      present study indicated that livin may be a promising target in clinical therapy
      of mid-distal rectal cancer.

PMID- 29344222
TI  - Herbal compound Teng-Long-Bu-Zhong-Tang inhibits metastasis in human RKO colon
      carcinoma.
AB  - Metastasis is one of the primary obstacles to the successful treatment of
      colorectal cancer. Teng-Long-Bu-Zhong-Tang (TLBZT) is a modern Chinese herbal
      formula that may be useful in the treatment of metastatic colorectal cancer. The
      present study evaluated the effects of TLBZT on lung metastasis in human RKO
      colon carcinoma cells injected into mice via the tail vein. The results
      demonstrated that TLBZT inhibited the metastasis of human RKO colon carcinoma
      cells to the lungs. TLBZT downregulated the expression of LOX and hypoxia
      inducible factor 1alpha. TLBZT also inhibited the expression of integrins alphaV
      and beta3 and the phosphorylation of focal adhesion kinase. These results
      indicate that TLBZT inhibits the lung metastasis of RKO colon carcinoma by
      regulating the expression of multiple genes. The results of the present study
      provide a new basis for the management of colorectal cancer metastasis using
      treatments derived from Chinese herbs.

PMID- 29344223
TI  - Application of intensity-modulated radiation therapy in the treatment of
      nasopharyngeal carcinoma.
AB  - The objective of the present study was to investigate the application values of
      the intensity-modulated radiation therapy (IMRT) and the three-dimensional
      conformal radiation therapy (3D-CRT) in the treatment of nasopharyngeal carcinoma
      (NPC). A total of 124 patients diagnosed with nasopharyngeal carcinomas were
      included into the study and randomly divided into the control group and the
      observation group, with 62 patients in each group. The 3D-CRT combined with
      postoperative chemotherapy were performed on the control group and the
      observation group received IMRT combined with postoperative chemotherapy, and
      then were followed up for a median duration of 25.5 months. Comparison of the
      survival analysis of the two groups showed no differences between them in terms
      of the total effective rate and effectiveness (P>0.05), or radiotherapy
      complications (P>0.05). In addition, no significant differences between the two
      groups were found in the follow-up local tumor control probability (TCP),
      regional lymph node control rate, distant metastasis-free rate, tumor-free
      survival rate, recurrence rate and overall survival rate (P>0.05). Furthermore,
      there was no difference between the two groups in the overall score of quality of
      life (P>0.05). The present study concludes that the IMRT and the 3D-CRT have
      almost the same short-term and long-term clinical effects in the treatment of
      nasopharyngeal carcinoma and both of them have high effectiveness and safety.

PMID- 29344224
TI  - Long-term outcomes of microwave endometrial ablation for treatment of patients
      with menorrhagia: A retrospective cohort study.
AB  - This study aimed to describe the long-term outcomes of patients with menorrhagia
      treated with microwave endometrial ablation (frequency, 2.45 GHz), as well as to
      identify factors associated with recurrence or re-surgery. This retrospective
      cohort study was conducted from 2007 to 2015 at Shimane University Hospital in
      Japan. Patients with severe menorrhagia and a desire to preserve their uterus
      were included in the study. Clinical factors associated with recurrence of
      menorrhagia or re-surgery were analyzed with a multivariable logistic regression
      model. Of 160 microwave endometrial ablation candidates, 100 had uterine myomas,
      20 adenomyosis, 26 functional excessive menstruation, and 12 endometrial polyps.
      In the full cohort, age (<40) and uterine cavity length (>=10) were associated
      with recurrence of menorrhagia and re-surgery. Among patients with myomas, age
      (<48) and number of myomas (>=4) were associated with recurrence, and largest
      myoma size (>=5) and preoperative hemoglobin level (<9 mg/dl) were associated
      with re-surgery. Among subjects with adenomyosis, uterine cavity length (>=10)
      was associated with recurrence. Microwave endometrial ablation is thought to be a
      highly efficacious method to control menorrhagia caused by functional bleeding
      and endometrial polyps. However, microwave endometrial ablation may be less
      effective for patients younger than 48 years with myomas, especially those with 4
      or more myomas, or with a myoma 5 cm or larger in size, and for patients with
      adenomyosis who have a thickened myometrium. These clinical factors may be useful
      predictors of success in selecting candidates for microwave endometrial ablation.

PMID- 29344225
TI  - Metformin enhances the chemosensitivity of hepatocarcinoma cells to cisplatin
      through AMPK pathway.
AB  - This study investigated the effect of metformin on chemosensitivity of
      hepatocarcinoma cells to cisplatin and the possible mechanism. HepG2 and Huh-7
      hepatoma cells were treated with cisplatin at concentrations of 0, 2, 4, 6, 8 and
      10 uM for 48 h. Proliferation of HepG2 and Huh-7 hepatoma cells were detected by
      MTT assay. Apoptosis of hepatocellular carcinoma cells was detected by flow
      cytometry. Western blot analysis was used to detect the expression of 5
      monophosphate-activated protein kinase (AMPK) and p-AMPK protein. Proliferative
      activity of HepG2 and Huh-7 cells decreased with the increase of cisplatin
      concentration. After adding metformin, proliferation ability of hepatocarcinoma
      cells was significantly reduced. Apoptosis rate of the metformin was
      significantly higher than that of the control group, and apoptosis rate of the
      cisplatin + metformin was significantly higher than that of the cisplatin group.
      There was no significant difference in expression level of AMPK protein found
      between control, metformin, cisplatin and cisplatin + metformin group. Compared
      with the control, ratio of p-AMPK/AMPK in metformin group was increased, and
      ratio of p-AMPK/AMPK in cisplatin + metformin was significantly higher than that
      in cisplatin group. Activity of cells in cisplatin + metformin + compound C (AMPK
      pathway blocker) group was significantly higher than that of cisplatin +
      metformin, while apoptosis of cells in cisplatin + metformin + compound C (AMPK
      pathway blocker) was significantly lower than that of cisplatin + metformin
      group. In conclusion, metformin can inhibit the proliferation, promote apoptosis
      and enhance the chemosensitivity of hepatocarcinoma cells to cisplatin through
      AMPK pathway.

PMID- 29344226
TI  - Analysis of survival and prognosis of 298 gastric adenocarcinoma patients with no
      distant metastasis.
AB  - This study investigated the survival and prognosis of 298 gastric adenocarcinoma
      patients with no distant metastasis. For analysis and comparison of the prognosis
      of patients, a retrospective analysis was performed in 298 patients with perfect
      clinical data and follow-up data who received the D2 resections for gastric
      cancer in Shandong Provincial Hospital Affiliated to Shandong University between
      January, 2005 and January, 2012, and were diagnosed as gastric adenocarcinoma
      with no distant metastasis in postoperative pathological examination. Among the
      gastric adenocarcinoma patients without distant metastasis, we found that
      differences of sex, age, differentiation and position of tumor had no statistical
      significance (P>0.05), while comparisons of the tumor diameter, regional
      lymphatic metastasis, vascular invasion and pathological TNM stages (pTNM; T for
      tumor, N for lymph node and M for metastasis) showed statistical significance
      (P<0.05). One-way analysis of variance (ANOVA) indicated the correlation between
      the prognosis of gastric adenocarcinoma patients and tumor diameter, regional
      lymphatic metastasis, vascular invasion and pTNM stages of patients (P<0.05).
      Multivariate analysis of Cox regression models was performed for discovering the
      factors associated with the prognosis of patients, and the results suggested that
      position of tumor (P=0.016), regional lymphatic metastasis (P=0.042), vascular
      invasion (P=0.021) and pTNM stage (P=0.009) were the independent risk factors
      affecting the prognosis of gastric adenocarcinoma patients. During 60-month
      follow-up, the median survival duration of gastric adenocarcinoma patients with
      no distant metastasis was 38 months, while the 5-year accumulate survival rate
      was 49.3%. The results indicated that in gastric adenocarcinoma patients without
      distant metastasis, tumor diameter, regional lymphatic metastasis, vascular
      invasion and pTNM stage are major indicators affecting the prognosis of patients.

PMID- 29344227
TI  - Sirolimus treatment for cirrhosis or hepatocellular carcinoma patients
      accompanied by psoriasis after liver transplantation: A single center experience.
AB  - There is currently no consensus on the most suitable therapeutic approach for
      psoriasis (PS) co-existing with posthepatic cirrhosis (PCs) and hepatocellular
      carcinoma (HCC) following liver transplantation (LT). The present study provides
      an analysis of the therapeutic experience of such patients. Five LT recipients
      (two with PC and three with HCC) with accompanying PS were included. The
      induction program consisted of methylprednisolone plus basiliximab treatment. The
      initial postoperative treatment scheme consisted of tacrolimus (FK506) plus
      mycophenolate mofetil (MMF) and hormone; the latter was withdrawn 1 week after
      LT. The patients with PC had been using FK506 with or without a postoperative MMF
      program; the patients with HCC and recurrence of PS had been switched to a
      sirolimus (SRL)-based replacement therapy. Furthermore, all patients received
      anti-hepatitis B virus (HBV) therapy. The patients were followed up after 8.3+/
      1.5 years. There was a positive correlation between HBV-DNA copy numbers, and
      psoriatic area and severity index (PASI) scores (r=0.97; P=0.006). The PASI
      scores were decreased significantly at 6 months following surgery compared with
      pre-transplantation (P<0.05). The patients who had received the FK506-based
      treatment experienced PS recurrence two years post-transplantation. The PASI
      scores increased significantly (P<0.05) and then declined gradually, maintaining
      a stable level (P<0.05) by 1 year after switching to the SRL-based treatment. The
      patients who had received the SRL-based treatment exhibited no recurrence of PS.
      The results of the present study suggest that SRL therapy provides a promising
      novel treatment method for patients with PS following LT that may be superior to
      tacrolimus treatment. When co-existing HBV is present pre-transplantation,
      regular injection of human hepatitis B immunoglobulin should be used to prevent
      the HBV from relapsing or aggravating the PS.

PMID- 29344228
TI  - Expression and clinical significance of ATM and PUMA gene in patients with
      colorectal cancer.
AB  - The expression of ataxia-telangiectasia mutated (ATM) and p53 upregulated
      modulator of apoptosis (PUMA) genes in patients with colorectal cancer were
      investigated, to explore the correlation between the expression of ATM and PUMA
      and tumor development, to evaluate the clinical significance of ATM and PUMA in
      the treatment of colorectal cancer. Quantitative real-time PCR was used to detect
      the expression of ATM and PUMA in tumor tissue and adjacent healthy tissue of 67
      patients with colorectal cancer and in normal colorectal tissue of 33 patients
      with colorectal polyps at mRNA level. The expression level of ATM mRNA in
      colorectal cancer tissues was significantly higher than that in normal mucosa
      tissues and adjacent non-cancerous tissue (P<=0.05), while no significant
      differences in expression level of ATM mRNA were found between normal mucosa
      tissues and adjacent noncancerous tissue (P=0.07). There was a negative
      correlation between the expression of ATM mRNA and the degree of differentiation
      of colorectal cancer (r= -0.312, P=0.013), while expression level of ATM mRNA was
      not significantly correlated with the age, sex, tumor invasion, lymph node
      metastasis or clinical stage (P>0.05). Expression levels of PUMA mRNA in
      colorectal cancer tissues, adjacent noncancerous tissue and normal tissues were
      0.68+/-0.07, 0.88+/-0.04 and 1.76+/-0.06, respectively. Expression level of PUMA
      mRNA in colorectal cancer tissues and adjacent noncancerous tissue was
      significantly lower than that in normal colorectal tissues (P<0.05). The results
      showed that ATM mRNA is expressed abnormally in colorectal cancer tissues.
      Expression of PUMA gene in colorectal carcinoma is downregulated, and is
      negatively correlated with the occurrence of cancer.

PMID- 29344229
TI  - Preparation and characterization of the Adriamycin-loaded amphiphilic chitosan
      nanoparticles and their application in the treatment of liver cancer.
AB  - In the present study, two nanoparticles including lactose myristoyl carboxymethyl
      chitosan (LMCC) and algal polysaccharide myristoyl carboxymethyl chitosan (AMCC),
      were obtained for hepatic-targeted Adriamycin (ADM) drug delivery systems. ADM
      was successfully loaded into the LMCC or AMCC nanoparticle by dialysis. The
      release function and liver targeting of the nanoparticles was explored, and it
      was revealed that ADM release from the nanoparticles was greatest at acidic pH
      5.5. ADM-conjugated nanoparticles were readily taken up by HU7 human
      hepatocellular carcinoma cells, relative to HT22 mouse hippocampal neuron cells
      in vitro. In vivo, ADM-loaded nanoparticles had significant antitumor efficacy
      with a 62.7% inhibition rate, followed by ADM and ADM-AMCC (51.2 and 42.5%,
      respectively). The tissue distribution study confirmed that ADM-LMCC had an
      improved liver delivery efficacy, by comparison with ADM. Furthermore, a series
      of safety studies, including hemolysis, acute toxicity and organ toxicity,
      revealed that the ADM-loaded LMCC and AMCC nanoparticles had advantages over the
      commercially available injectable preparation of Adriamycin hydrochloride, in
      terms of low toxicity levels and increased tolerated dose. These results
      indicated that LMCC is a promising carrier for injectable ADM nanoparticle and
      ADM-conjugated nanoparticles may improve the efficacy of ADM by hepatic
      targeting.

PMID- 29344230
TI  - Reduced miR-105-1 levels are associated with poor survival of patients with non
      small cell lung cancer.
AB  - Altered expression of microRNAs (miRNAs or miRs) contributes to lung
      carcinogenesis. The present study performed an in silico analysis of
      differentially expressed miRNAs in different peripheral blood samples from
      patients with various diseases vs. controls using the Gene Expression Omnibus
      (GEO) database data, and assessed miR-105-1 expression in 32 normal lung and 142
      non-small cell lung cancer (NSCLC) tissue samples using reverse transcription
      quantitative polymerase chain reaction. Survival data were calculated using
      Kaplan-Meier curves and a log-rank test. The stepwise forward Cox regression
      model was performed for univariate and multivariate analyses of independent
      predictor of overall survival (OS) of patients. The data on in silico and tissue
      microarray analyses of miRNA expression revealed reduced miR-105-1 expression in
      different types of human cancer, particularly in NSCLC. The level of miR-105-1
      expression was confirmed to be downregulated in NSCLC tissues compared with that
      in normal lung tissues. Reduced miR-105-1 expression was associated with larger
      tumor size as well as poor OS and disease-free survival (DFS) of patients.
      Multivariate survival analysis demonstrated that reduced miR-105-1 expression and
      tumor size were independent predictors for OS of NSCLC patients. In conclusion,
      reduced miR-105-1 expression in NSCLC tissues is associated with poor OS and DFS
      of NSCLC patients.

PMID- 29344231
TI  - Expression of Beclin 1 and Bcl-2 in pancreatic neoplasms and its effect on
      pancreatic ductal adenocarcinoma prognosis.
AB  - Aberrant expression of Beclin 1 and B-cell lymphoma-2 (Bcl-2) has been identified
      in a variety of human tumors; however, little information is available for
      pancreatic neoplasms. The present study analyzed the expression of Beclin 1 and
      Bcl-2 in pancreatic ductal adenocarcinoma (PDAC) and solid pseudopapillary
      neoplasm (SPN) of the pancreas, and evaluated their prognostic significance for
      PDAC. The present study included 117 PDAC, 43 SPN and 32 chronic pancreatitis
      (CP) cases. Levels of Beclin 1 and Bcl-2 expression were evaluated
      semiquantitatively by immunohistochemistry, and their correlation with the
      survival of patients with PDAC was determined. Beclin 1 was upregulated in 74
      (63.2%) PDAC, 26 (60.5%) SPN, and 14 (43.8%) CP cases. Bcl-2 was upregulated in
      38 (32.5%) PDAC, 11 (25.6%) SPN and 24 (75.0%) CP cases. High Beclin 1 and low
      Bcl-2 expression was significantly correlated with poor differentiation and
      distant metastasis in PDAC, and associated with the presence of nuclear
      pleomorphism in SPN and with advanced Tumor-Node-Metastasis stage in PDAC. Beclin
      1 and Bcl-2 levels were inversely correlated in PDAC, whereas they were
      positively correlated in SPN. Low Beclin 1 and high Bcl-2 expression was
      associated with improved disease-free survival and overall survival (OS).
      However, the association of Beclin 1 with survival was not significant in the Cox
      analysis, whereas Bcl-2 expression was significantly correlated with OS in the
      multivariate analysis. In conclusion, Beclin 1 upregulation exacerbated the
      progression and aggressiveness of pancreatic neoplasms, and Bcl-2 downregulated
      expression was an independently poor prognostic factor for PDAC.

PMID- 29344232
TI  - Novel combination of paraspinal keyhole surgery with a tubular retractor system
      leads to significant improvements in lumbar intraspinal extramedullary
      schwannomas.
AB  - The aim of the present study was to investigate the efficacy of combining
      paraspinal keyhole surgery with a tubular retractor system for the microsurgical
      removal of lumbar intraspinal extramedullary schwannomas. A retrospective
      analysis was conducted of 56 patients with lumbar intraspinal extramedullary
      schwannomas who were treated using the microsurgical paraspinal keyhole approach
      with a tubular retractor system. The mean +/- standard deviation was calculated
      for the following parameters: Surgery time (96.21+/-14.64 min), hemorrhagic
      volume (28.54+/-9.72 ml), bed rest (2.55+/-0.5 days) and hospital stay (5.68+/
      0.72 days). Two patients presented with cerebrospinal fluid leakage and one
      patient exhibited a nerve root injury. At a 6-month follow-up visit,
      postoperative Japanese Orthopedic Association (JOA) and visual analog scale (VAS)
      scores were evaluated. The mean +/- standard deviation JOA scores were 12.00+/
      2.07 for preoperative, 14.73+/-2.05 for 1 week postoperative, 20.07+/-2.32 for 3
      months postoperative and 21.75+/-2.18 for 6 months postoperative. The improvement
      rate was 16.07, 47.48 and 59.77%, respectively. The mean +/- standard deviation
      VAS scores were 6.64+/-1.31 for preoperative, 3.82+/-1.51 for 1 week
      postoperative, 2.11+/-1.17 for 3 months postoperative and 1.50+/-1.51 for 6
      months postoperative. The JOA and VAS scores improved significantly (P<0.05).
      Magnetic resonance imaging and computed tomography were performed preoperatively,
      immediately following surgery and at the 6-month postoperative visit to confirm
      the efficacy of the resections and evaluate spinal stability. No residual tumors
      were identified at follow-up. No alterations in the stability of the spine were
      observed postoperatively. The combination of the microsurgical paraspinal keyhole
      approach with the tubular retractor system was successful in treating lumbar
      intraspinal extramedullary schwannomas. The surgical approach was associated with
      decreased hemorrhages, decreased duration of hospital stay, faster recovery and
      improved postoperative maintenance of spinal stability.

PMID- 29344233
TI  - Lidamycin decreases CD133 expression in hepatocellular carcinoma via the Notch
      signaling pathway.
AB  - Cluster of differentiation (CD)133 is considered a molecular marker of cancer
      stem cells in hepatocellular carcinoma. In the present study, the effect of
      lidamycin (LDM) on CD133 expression in hepatocellular carcinoma (Huh7 cells) was
      evaluated and the potential molecular mechanism was investigated. Flow cytometry
      analysis, as well as sorting, sphere formation and western-blot assays, were
      performed in vitro to explore the effects of LDM on CD133 expression. A
      subcutaneous tumor model in nude mice was used to observe the effects of LDM on
      tumor volume and CD133 protein in vivo. To investigate the potential underlying
      molecular mechanism, Notch signaling pathway activity was detected by western
      blot analysis and reverse transcription-quantitative polymerase chain reaction.
      The proportion of CD133+ cells and the expression of CD133 protein were revealed
      to be downregulated by LDM. Sphere formation of sorted CD133+ cells was
      suppressed 7 days after LDM treatment. In addition, LDM inhibited tumor volume
      formed from sorted CD133+ cells and CD133 protein level in vivo. LDM decreased
      the mRNA level of NOTCH1, Hes1 (Hes family BHLH transcription factor 1) and Hey1
      (Hes-related family BHLH transcription factor with YRPW motif 1) genes;
      consequently, the protein expression of NOTCH1, Notch intracellular domain, Hes1
      and Hey1 was decreased by LDM. Downregulation of the Notch signaling pathway by
      LDM was enhanced through combination with N-[N-(3,5-difluorophenacetyl)-L-alanyl]
      S-phenylglycine t-butyl ester. In brief, these data suggest that LDM suppresses
      CD133 expression via the Notch signaling pathway, indicating the potential
      mechanism of LDM on CD133 and the benefits for further clinical application.

PMID- 29344234
TI  - An oncogenic function of retinoic acid receptor-alpha in the development of
      laryngeal squamous cell carcinoma.
AB  - The aberrant expression of retinoic acid receptor-alpha (RARalpha) has been
      reported in various types of cancer. However, its association with the prognosis
      and development of laryngeal squamous cell carcinoma (LSCC) has not yet been
      determined. Therefore, the present study aimed to examine the expression and
      function of RARalpha in patients with LSCC. The expression of RARalpha in LSCC
      tissues was investigated using immunostaining. An MTT assay and flow cytometry
      analysis were also performed to investigate the function of RARalpha in the
      proliferation and cell cycle of LSCC cells. The expression of RARalpha was
      significantly elevated in LSCC tissues compared with adjacent noncancerous
      tissues (78.1 vs. 6.3%, P<0.05). The overexpression of RARalpha was associated
      with poorly differentiated features of LSCC (P<0.05). Furthermore, the
      downregulation of RARalpha inhibited the proliferation of LSCC cells, and
      arrested the cell cycle at the G1 phase via upregulation of cyclin dependent
      kinase inhibitor 1A, which may be associated with inhibition of the protein
      kinase B signaling pathway. Therefore, the overexpression of RARalpha may
      contribute to the development of LSCC through the regulation of the cell cycle.
      The results of the present study provide evidence that RARalpha serves an
      important function in LSCC development and may be a potential therapeutic target
      or prognostic predictor for LSCC.

PMID- 29344235
TI  - Metronomic chemotherapy remodel cancer-associated fibroblasts to decrease
      chemoresistance of gastric cancer in nude mice.
AB  - The present study aimed to evaluate whether capecitabine or 5-fluorouracil (5-Fu)
      chemotherapy with the metronomic pattern may cause significant chemoresistance
      compared with the traditional pattern, and whether CAFs are involved in drug
      resistance. SGC-7901 cells were subcutaneously injected into the nude mice, and
      the mice were divided into five groups: The control group, intraperitoneally
      injected with normal saline; the 5-Fu conventional dose group [5-Fu maximum
      tolerated dose (MTD) group], intraperitoneally injected with 50 mg/kg, twice per
      week for 2 weeks, with an 1-week discontinuation for 6 weeks; the capecitabine
      conventional dose group (capecitabine MTD group), intragastric 500 mg/kg, twice
      per week for 2 weeks, with a 1-week discontinuation for 6 weeks; the 5-Fu
      metronomic group [5-Fu low-dose metronomic (LDM) group], intraperitoneally
      injected with 15 mg/kg, twice a week for 6 weeks; and the capecitabine metronomic
      group (capecitabine LDM group), intragastric administration at 200 mg/kg, twice a
      week for 6 weeks. The chemotherapy resistance markers [glutathione transferase Pi
      (GSTP) and multidrug resistance protein 1 (MDR1)] were detected by
      immunohistochemical staining (IHC), and the association of the expression of
      these markers with the chemotherapy administration patterns was analyzed.
      Vascular endothelial growth factor (VEGF) and the cancer-associated fibroblast
      (CAF) marker alpha-smooth muscle actin were also examined by IHC to illustrate
      the possible mechanism of chemoresistance. The expression of GSTP and MDR1 in the
      MTD groups was significantly higher compared with those of the LDM groups
      (P<0.01). Furthermore, the number of CAFs and the level of VEGF in the MTD groups
      were significantly higher compared with those of the LDM groups (P<0.05). The low
      dose metronomic chemotherapy did not increase the risk of chemoresistance
      compared with the conventional dose traditional chemotherapy in terms of
      capecitabine or 5-Fu, the increasing amount of CAFs in the microenvironment of
      cancer cell following therapy may protect cell from capecitabine or 5-Fu via
      producing VEGF to increase vascularization.

PMID- 29344236
TI  - Alterations in expression levels of genes in p53-related pathways determined
      using RNA-Seq analysis in patients with breast cancer following CIK therapy.
AB  - The present study aimed at investigating the underlying molecular mechanisms for
      patients following cytokine-induced killer (CIK) therapy, particularly involving
      the alterations in p53-associated signaling pathways, to elucidate whether CIK
      therapy serves a function in cancer treatment. Samples of blood were collected
      from patients with breast cancer prior to and following CIK therapy. Two group
      samples were used for RNA sequencing (RNA-Seq) to determine the alterations in
      gene expression levels following CIK therapy and one for the quantitative
      polymerase chain reaction (qPCR), to analyze the reliability of RNA-Seq results.
      The genes that may encode proteins associated with p53 pathways were selected and
      analyzed. The expression levels of 8 genes were analyzed, including tumor
      suppressor protein 53 (TP53), murine double minute homolog 2 (MDM2), ribosomal
      protein L11 (RPL11), ribosomal protein S23 (RPS23), sirtuin 1, histone
      deacetylase 1, tuberous sclerosis complex 1 (TSC1) and mechanistic target of
      rapamycin (mTOR), and alterations in expression levels following CIK therapy were
      determined. However, only RPL11 and RPS23 were identified to exhibit marked
      alterations in expression levels (FDR <0.05), which was considered to be due to
      individual distinctions. qPCR analysis revealed that the expression levels of the
      RPL11, TP53 and TSC1 genes were downregulated, and those of the RPS23 and MDM2
      genes were upregulated following CIK therapy. Only MDM2 exhibited a marked
      alteration in the gene expression level following CIK therapy. Alterations in the
      expression levels of TP53, RPL11 and TSC1 were associated with those of MDM2,
      RPS23 and mTOR, respectively.

PMID- 29344237
TI  - Chloroform extract of Hedyotis diffusa Willd inhibits viability of human
      colorectal cancer cells via suppression of AKT and ERK signaling pathways.
AB  - Hedyotis diffusa Willd (HDW) is a widely used traditional Chinese medicine in
      clinical therapy to treat various types of cancer, including colorectal cancer
      (CRC), but its effective polar fractions and functional mechanisms remain
      unclear. The aim of the present study was to determine the most effective extract
      of HDW and to investigate its effects on the regulation of CRC cell proliferation
      and apoptosis, as well as to investigate the underlying molecular mechanisms. The
      results demonstrated that the chloroform extract of HDW (CEHDW) exhibited the
      most anticancer ability. Furthermore, results of the MTT assay, colony formation,
      carboxyfluorescein diacetate succinimidyl ester assay and annexin V/propidium
      iodide staining suggested that CEHDW significantly inhibits proliferation and
      promotes apoptosis in the SW620 CRC cell line. Additionally, reverse
      transcription-polymerase chain reaction and western blot analysis demonstrated
      that CEHDW treatment downregulated the expression of Survivin, proliferating cell
      nuclear antigen, Cyclin D1, cyclin-dependent kinase 4 and B-cell lymphoma 2 (Bcl
      2), and upregulated the expression of Bcl-2-associated X protein at the mRNA and
      protein levels. CEHDW also decreased the phosphorylation of protein kinase B
      (AKT) and extracellular-signal-regulated kinase (ERK), which indicated that the
      suppression of the AKT and ERK signaling pathways may be one of the underlying
      molecular mechanisms by which CEHDW exhibited its anticancer effect. Thus, CEHDW
      may be a promising agent for anticancer therapy.

PMID- 29344238
TI  - Sophoridine suppresses cell growth in human medulloblastoma through FoxM1, NF
      kappaB and AP-1.
AB  - Sophoridine is an alkaloid extracted from Sophora alopecuroides that has
      extensive pharmacological actions. In the present study, the effect of
      sophoridine on cell growth of human medulloblastoma and its mechanism were
      investigated. Human medulloblastoma D283-Med cells were incubated with 0, 0.5, 1
      or 2 mg/ml sophoridine for 24, 48 or 72 h. Cell proliferation and cytotoxicity
      were analyzed using MTT and lactate dehydrogenase assays, respectively. Next,
      analyses of cell apoptosis and caspase-3/8 activity were performed using flow
      cytometry or spectrophotometry, respectively. Lastly, the change in FoxM1, TrkB,
      BDNF, NF-kappaB and AP-1 expression was investigated using western blot analysis.
      In the present study, treatment with sophoridine significantly suppressed cell
      growth and induced apoptosis in human medulloblastoma cells. In addition,
      sophoridine significantly increased cytotoxicity and caspase-3/8 activity in
      human medulloblastoma. Finally, it was found that sophoridine suppresses the
      protein expression of FoxM1, TrkB, BDNF NF-kappaB and AP-1 in human
      medulloblastoma cells. The present study suggests that sophoridine suppresses
      cell growth of human medulloblastoma through the inhibition of the FoxM1, NF
      kappaB and AP-1 signaling pathway.

PMID- 29344239
TI  - Prognostic impact of preoperative serum interleukin-6 levels in patients with
      early-stage oral squamous cell carcinoma, defined by sentinel node biopsy.
AB  - Failure to detect recurrence and lymph node metastasis early represents a
      fundamental barrier to the improvement of survival rate in early stage oral
      squamous cell carcinoma (OSCC). The present study evaluated the association
      between serum interleukin-6 (IL-6) level and clinical outcomes in patients with
      early stage OSCC patients defined by sentinel node biopsy (SNB). A total of 53
      patients with clinical stage I/II OSCC who underwent SNB were enrolled. SNB was
      determined by a radioisotope method, and was evaluated by histopathological
      examination and genetic analysis. Preoperative sera were measured for IL-6 by
      ELISA. In the clinical stage I/II patients, disease-free survival (DFS) was
      demonstrated to be higher in patients with negative SNB compared with patients
      with positive SNB. In total, 13 patients were demonstrated to exhibit lymph node
      metastasis by SNB or were reclassified to pathological stage T4 subsequent to
      analysis of the surgically resected specimens. Thus, 40 patients were diagnosed
      with early stage OSCC. Of these 40 patients, DFS of the patients with low serum
      IL-6 was significantly higher compared with the patients with high serum IL-6
      (P=0.012). In 19 patients with negative SNB and low serum IL-6, the disease-free
      rate was 100%. These findings suggested that SNB staging and serum IL-6 level
      have a high prognostic value in patients with early stage OSCC. Additional
      investigation and longer follow-up times are warranted to improve understanding
      of the group of patients that may benefit from this procedure.

PMID- 29344240
TI  - CXCL5 as an autocrine or paracrine cytokine is associated with proliferation and
      migration of hepatoblastoma HepG2 cells.
AB  - C-X-C motif chemokine ligand 5 (CXCL5) is a CXC-type chemokine that is a crucial
      inflammatory mediator and a powerful attractant for granulocytic immune cells.
      Increasing evidence has indicated that CXCL5 is involved in the tumorigenesis of
      various malignancies. The present investigation demonstrated that CXCL5 was
      expressed in both hepatoblastoma HepG2 cells and liver stellate LX-2 cells, and
      CXCL5's receptor C-X-C chemokine receptor type 2 (CXCR2) was expressed in HepG2
      cells by reverse transcription-polymerase chain reaction (RT-PCR), western
      blotting and ELISA assays. Cell counting kit-8, colony formation and Transwell
      assays revealed that exogenous CXCL5 expression efficiently promoted
      proliferation, colony formation and migration of HepG2 cells. To explore the
      autocrine and paracrine roles of CXCL5 in the oncogenic potential of HepG2 cells,
      HepG2 cells overexpressing CXCL5 and LX-2 cells overexpressing CXCL5 were
      successfully constructed by gene transfection. Similarly, overexpression of CXCL5
      in HepG2 also enhanced proliferation, colony formation and migration of HepG2
      cells. Furthermore, the condition medium of LX-2 cells overexpressing CXCL5
      affected the proliferation and migration of HepG2 cells. RT-PCR and western
      blotting assays were also conducted to explore whether overexpression of CXCL5 in
      HepG2 modulated the expression of genes. The results revealed that overexpression
      of CXCL5 regulated the expression of several genes, including N-myc downregulated
      gene 3,w B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein, P53, vascular
      endothelial growth factor, interleukin (IL)-18, IL-1beta and cystathionine-gamma
      lyase. In conclusion, the present findings indicate that CXCL5/CXCR2 axis
      contributes to the oncogenic potential of hepatoblastoma via autocrine or
      paracrine pathways by regulating expression of genes associated with the
      progression of carcinoma.

PMID- 29344241
TI  - Combined pitavastatin and dacarbazine treatment activates apoptosis and autophagy
      resulting in synergistic cytotoxicity in melanoma cells.
AB  - Melanoma is an aggressive skin cancer and its incidence is increasing faster than
      any other type of cancer. Whilst dacarbazine (DTIC) is the standard chemotherapy
      for metastatic melanoma, it has limited success. Statins, including pitavastatin,
      have been demonstrated to have a range of anti-cancer effects in a number of
      human cancer cell lines. The present study therefore explored the anti-cancer
      activity of combined DTIC and pitavastatin in A375 and WM115 human melanoma
      cells. Cell survival assays demonstrated that combined DTIC and pitavastatin
      treatment resulted in synergistic cell death. Cell cycle analyses further
      revealed that this combined treatment resulted in a G1 cell cycle arrest, as well
      as a sub-G1 population, indicative of apoptosis. Activation of apoptosis was
      confirmed by Annexin V-fluorescein isothiocyanate/propidium iodide double
      staining and an increase in the levels of active caspase 3 and cleaved poly (ADP
      ribose) polymerase. Furthermore, it was demonstrated that apoptosis occurs
      through the intrinsic pathway, evident from the release of cytochrome c. Finally,
      combined DTIC and pitavastatin treatment was demonstrated to also activate
      autophagy as part of a cell death mechanism. The present study provides novel
      evidence to suggest that the combined treatment of DTIC and pitavastatin may be
      effective in the treatment of melanoma.

PMID- 29344242
TI  - In vivo and in vitro induction of the apoptotic effects of oxysophoridine on
      colorectal cancer cells via the Bcl-2/Bax/caspase-3 signaling pathway.
AB  - Oxysophoridine (OSR) is a major active alkaloid extracted from
      Sophoraalopecuroides L. The aim of the present study was to investigate the
      induction of the apoptotic effects of OSR on colorectal cancer cells in vivo and
      in vitro. The results of the MTT and colony formation assays demonstrated that
      the proliferation of HCT116 cells was inhibited by OSR in vitro. The
      characteristics of cellular apoptosis in OSR-treated HCT116 cells were analyzed
      by Hoechst 33258 staining. It was also observed that the expression of caspase-3,
      B-cell lymphoma-2 (Bcl-2) associated X protein (Bax) and cytochrome c increased
      significantly upon OSR treatment. However, the expression of Bcl-2 and poly ADP
      ribose polymerase-1 (PARP-1) was downregulated in OSR-treated cells compared with
      untreated cells. The in vivo experiments identified that OSR significantly
      inhibited the growth of the transplanted mouse CT26 tumor tissue, upregulated the
      expression of caspase-3, Bax and cytochrome c and downregulated the expression of
      Bcl-2 and PARP-1, as detected by reverse transcription-quantitative polymerase
      chain reaction and western blotting. It may be concluded that OSR significantly
      induced apoptotic effects on colorectal cancer cells in vivo and in vitro, and
      that its mechanism may be associated with the Bcl-2/Bax/caspase-3 signaling
      pathway.

PMID- 29344243
TI  - T-cell immunoglobulin and mucin domain-containing protein-3 and galectin-9
      protein expression: Potential prognostic significance in esophageal squamous cell
      carcinoma for Chinese patients.
AB  - The aim of the present study was to investigate the expression levels of the T
      cell immunoglobulin and mucin domain-containing protein-3 (TIM-3) and galectin-9
      proteins and their clinical value in esophageal squamous cell carcinoma (ESCC) in
      Chinese patients. The expression profiles of TIM-3 and galectin-9 in ESCC were
      determined by the immunohistochemical analysis of the postoperative pathological
      specimens of 45 patients with ESCC; a chi2 test was used to evaluate the
      association of TIM-3 and galectin-9 expression with clinicopathological
      parameters, in addition to univariate and multivariate Cox's proportional hazards
      model to analyze the prognostic value of the expression of TIM-3 and galectin-9
      proteins. The proportion of samples exhibiting a high staining intensity for TIM
      3 and galectin-9 were 22.22 and 15.56%, respectively: these samples were termed
      the TIM-3 high-expression group (HEG) and galectin-9-HEG. There was a negative
      correlation between the expression of TIM-3 and galectin-9 (R=-0.71, P<0.001).
      The results of Kaplan-Meier survival analysis led to the conclusion that,
      compared with the TIM-3 low expression group (LEG), patients in the TIM-3-HEG
      exhibited a poorer overall survival rate (chi2=6.049, P=0.0139). By contrast,
      patients in the galectin-9-HEG exhibited a significantly better overall survival
      rate than those in the galectin-9-LEG (chi2=4.915, P=0.0266). However, the levels
      of TIM-3 and galectin-9 expression were not identified as independent indicators
      for the prognosis of patients with ESCC. As high TIM-3 and low galectin-9
      expression levels were associated with a poor prognosis for patients with ESCC in
      the present study, these proteins may be potential prognostic indicators for
      ESCC.

PMID- 29344244
TI  - Identification and validation of PSAT1 as a potential prognostic factor for
      predicting clinical outcomes in patients with colorectal carcinoma.
AB  - The aim of the present study was to explore the existence of known or candidate
      drug-target genes that are upregulated in colorectal cancer (CRC) and may serve
      as novel prognostic factors or therapeutic targets for this type of malignancy.
      An in silico analysis was conducted using the Oncomine tool to compare the
      expression levels of a list of drug-target genes between cancerous and normal
      tissues in 6 independent CRC cohorts retrieved from the Oncomine database.
      Phosphoserine aminotransferase 1 (PSAT1) was identified as the top-ranked
      upregulated gene in CRC tumors, and was highly expressed in patients with
      chemoresistant disease. Subsequently, the expression of PSAT1 was further
      experimentally validated using immunohistochemistry in an independent cohort of
      CRC specimens. The immunohistochemistry results demonstrated that PSAT1 was
      overexpressed in the CRC tissues compared with the normal colorectal tissues,
      which was consistent with the previous in silico analysis. Furthermore, PSAT1
      overexpression was associated with response to irinotecan, 5-fluorouracil and
      leucovorin chemotherapy, and with shorter survival time, and retained
      significance as an independent prognostic factor for CRC when subjected to the
      multivariate analysis with a Cox's proportional hazards model. Therefore, the
      present results implicate PSAT1 as a potential prognostic biomarker and a
      promising therapeutic target for CRC. Targeted PSAT1 inhibition in the treatment
      of CRC warrants further investigation.

PMID- 29344245
TI  - Overexpression of NEDD9 in renal cell carcinoma is associated with tumor
      migration and invasion.
AB  - Scaffold protein neural precursor cell expressed, developmentally downregulated 9
      (NEDD9) is a member of the Crk-associated substrate protein family and is known
      to be a biomarker in multiple cancer types. It serves a critical function in
      regulating cell proliferation, migration, invasion and survival. The objective of
      this study was to evaluate the potential effects of NEDD9 in renal cell carcinoma
      (RCC). The expression of NEDD9 was analyzed by immunohistochemistry, western
      blotting and reverse transcription-quantitative polymerase chain reaction. NEDD9
      protein and mRNA levels were significantly upregulated in RCC tissues compared
      with normal tissues (P<0.001). Furthermore, the NEDD9 immunostaining level was
      significantly associated with primary tumor stage and tumor, node, metastasis
      stage (P<0.05). High NEDD9 expression resulted in significantly lower survival
      rates for patients compared with normal NEDD9 expression (P<0.01). In addition,
      wound healing and transwell assays indicated that NEDD9 depletion by small
      interfering RNA significantly attenuated the migration and invasion of RCC cells
      (P<0.001). The present data suggested that NEDD9 may be a novel target for
      prevention and treatment of RCC metastasis and recurrence.

PMID- 29344246
TI  - Silibinin inhibits migration and invasion of the rhabdoid tumor G401 cell line
      via inactivation of the PI3K/Akt signaling pathway.
AB  - Rhabdoid tumors, which tend to occur prior to the age of 2 years, are one of the
      most aggressive malignancies and have a poor prognosis due to the frequency of
      metastasis. Silibinin, a natural extract, has been approved as a potential tumor
      suppressor in various studies, however, whether or not it also exerts its
      antitumor capacity in rhabdoid tumors, particularly with regards to tumor
      migration and invasion, is unclear. The rhabdoid tumor G401 cell line was used in
      the present in vitro study. An MTT assay was used to assess the cytotoxicity of
      silibinin on G401 cells, cell migration was studied using a wound healing assay
      and a Transwell migration assay, and cell invasion was determined using a
      Transwell invasion assay. The underlying mechanism in silibinin inhibited cell
      migration and invasion was investigated by western blot analysis and further
      confirmed using a specific inhibitor. Experimental results demonstrated that high
      doses of silibinin suppressed cell viability, and that low doses of silibinin
      inhibited cell migration and invasion without affecting cell proliferation. The
      phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway was
      involved in the silibinin-induced inhibition of metastasis. Silibinin inactivated
      the PI3K/Akt pathway, and inhibited cell migration and invasion, an effect that
      was further enhanced when LY294002, a classic PI3K inhibitor, was used
      concurrently. In general, silibinin inhibits migration and invasion of the
      rhabdoid tumor G401 cell line via inactivation of the PI3K/Akt signaling pathway
      and may be a potential chemotherapeutic drug to combat rhabdoid tumors in the
      future.

PMID- 29344247
TI  - Upregulation of the checkpoint protein CHFR is associated with tumor suppression
      in pancreatic cancers.
AB  - The checkpoint with forkhead-associated (FHA) domain and RING-finger (CHFR)
      protein was identified as a cell cycle checkpoint protein and E3 ubiquitin
      ligase. In the present study, the potential functions of CHFR in pancreatic
      cancer were investigated. CHFR expression was measured in five pancreatic cancer
      cell lines by reverse transcription- quantitative polymerase chain reaction and
      western blotting. Capan-1 cells stably expressing CHFR were established by
      lentiviral vector transfection. Cell proliferation was assessed using Cell
      Counting Kit-8, and cell migration/invasion assay was determined using Transwell
      assays. Cell cycle and apoptosis induced by gemcitabine or docetaxel were
      evaluated using flow cytometry. CHFR expression levels were also evaluated in
      pancreatic ductal adenocarcinoma (PDAC) tumor samples as well as adjacent non
      tumor tissues by immunohistochemistry. The significance of CHFR expression was
      determined, with respect to clinicopathological features and overall survival.
      Overexpression of CHFR in Capan-1 cells led to a decreased proliferative rate and
      reduced cell migration and invasion abilities. Results also indicated an increase
      in G1 phase cells in Capan-1 cells overexpressing CHFR. Docetaxel-induced
      apoptosis was inhibited in Capan-1 cells with CHFR-overexpression. A reduction in
      CHFR expression was detected in 51.9% of patients with PDAC, which significantly
      correlated with later T-stage. The results show CHFR functions as a tumor
      suppressor in pancreatic cancer, suggests its potential role in controlling the
      cell cycle of pancreatic cancer cells; however, CHFR overexpression is not a
      favorable factor in apoptosis induced by docetaxel.

PMID- 29344248
TI  - Survival prediction in patients with resectable colorectal liver metastases:
      Clinical risk scores and tumor response to chemotherapy.
AB  - Clinical risk scores and response to pre-operative chemotherapy are prognostic
      factors of colorectal liver metastases. The aim of the present study was to
      evaluate the effectiveness of combining these factors to predict patient survival
      and to select patients for curative therapy. The study included 189 patients who
      underwent hepatectomy following neo-adjuvant chemotherapy, for initially
      resectable colorectal liver metastases, between January 2005 and December 2015.
      Patients were stratified into four sub-groups: A1-2, low clinical risk scores
      with/without a response to pre-operative chemotherapy; and B1-2, high clinical
      risk scores with or without a response to pre-operative chemotherapy. Treatment
      and survival data were analysed. Survival was significantly longer in patients
      with low clinical risk scores and a response to pre-operative chemotherapy; these
      factors were confirmed as independent prognostic factors by multivariate
      analysis. Combining clinical risk score and chemotherapy response classification,
      patient survival was significantly longer for groups A1-2/B1 compared with for
      group B2, in which only 10.2% of patients were alive after 5 years. Of those with
      no response to first-line chemotherapy, survival was significantly longer in
      patients who responded to second-line chemotherapy. A combined clinical risk
      score and chemotherapy response classification may aid in identifying suitable
      candidates for potentially curative therapy.

PMID- 29344249
TI  - Estradiol suppresses phosphorylation of ERalpha serine 167 through upregulation
      of PP2A in breast cancer cells.
AB  - Aromatase inhibitors (AIs) are effective endocrine therapeutics for
      postmenopausal women with estrogen receptor (ER)alpha-positive breast cancer.
      However, the efficacy of the treatment is often limited by the onset of AI
      resistance, owing to the phosphorylation of ERalpha serine 167 (Ser167). Previous
      studies have indicated that hyperactivation of the phosphoinositide-3 kinase/RAC
      serine/threonine-protein kinase signaling pathway occurs in AI-resistant breast
      cancer models, which coincides with elevated levels of ERalpha phosphorylation at
      Ser167. The tumor suppressor serine/threonine-protein phosphatase 2A (PP2A)
      regulates the phosphatidylinositol 3-kinase/RAC serine/threonine-protein kinase
      signaling pathway. A previous study indicated that PP2A inhibition decreased
      ERalpha Ser167 phosphorylation and estradiol (E2)-independent cell growth. The
      present study investigated the potential relevance of PP2A in E2 deprivation
      resistant MCF-7 cells. E2 depletion reduced the susceptibility of MCF-7 cells to
      inhibitors of mechanistic target of rapamycin (mTOR) and significantly increased
      ERalpha Ser167 phosphorylation and decreased expression of PP2A. Conversely, long
      term E2-deprived (LTED) MCF-7 cells, a model of AI-resistant breast cancer,
      exhibited decreased ERalpha Ser167 phosphorylation and further upregulation of
      PP2A in E2-containing medium. The PP2A activator forskolin (FSK) significantly
      inhibited LTED cell proliferation by increasing the effect of everolimus (Eve),
      an mTOR inhibitor. In summary, the present study provides further evidence that
      PP2A represents a therapeutic target for AI-resistant breast cancer.

PMID- 29344250
TI  - Prevention of body weight loss and sarcopenia by a novel selective androgen
      receptor modulator in cancer cachexia models.
AB  - Cancer cachexia is a syndrome that impairs the quality of life and overall
      survival of patients, and thus the effectiveness of anticancer agents. There are
      no effective therapies for cancer cachexia due to the complexity of the syndrome,
      and insufficient knowledge of its pathogenesis results in difficulty establishing
      appropriate animal models. Previously, promising results have been obtained in
      clinical trials using novel agents including the ghrelin receptor agonist
      anamorelin, and the selective androgen receptor modulator (SARM) enobosarm to
      treat cachexia in patients with cancer. The present study examined the
      pharmacological effects of SARM-2f, a novel non-steroidal small molecule SARM, in
      animal models. SARM-2f increased body and skeletal muscle weight without
      significantly increasing the weight of the seminal vesicles or prostates of the
      castrated male rats. In the mice with tumor necrosis factor alpha-induced
      cachexia, SARM-2f and TP restored body weight, carcass weight, and food
      consumption rate. In the C26 and G361 cancer cachexia animal models, body and
      carcass weight, lean body mass, and the weight of the levator ani muscle were
      increased by SARM-2f and TP treatments. Tissue selectivity of SARM-2f was also
      observed in these animal models. The results demonstrate the anabolic effects of
      SARM-2f in a cytokine-induced cachexia model and other cancer cachexia models,
      and suggest that SARM-2f may be a novel therapeutic option for cachexia in
      patients with cancer.

PMID- 29344251
TI  - miR-218 inhibits acute promyelocytic leukemia cell growth by targeting BMI-1.
AB  - Acute promyelocytic leukemia (APL) is a subtype of acute myelocytic leukemia.
      Previous studies have reported a number of functions and therapeutic roles of
      microRNAs (miRs) in APL, and have suggested that miR-218 acts as a tumor
      suppressor in a number of types of human cancer; however, its role in APL remains
      unclear. In the present study, the expression of miR-218 and its effects on the
      viability and proliferation of HL-60 cells was investigated. Reverse
      transcription-quantitative polymerase chain reaction analysis demonstrated that
      miR-218 was frequently downregulated in APL marrow tissues compared with normal
      marrow tissues. Overexpression of miR-218 significantly inhibited cell
      proliferation, arrested the cell cycle in the G0/G1 phase and induced apoptosis.
      In addition, B-cell-specific Moloney murine leukemia virus integration site 1
      (BMI-1) mRNA expression was negatively associated with miR-218 expression; BMI-1
      mRNA and protein expression were downregulated following transfection with miR
      218 mimic. These results indicate that miR-218 functions as tumor suppressor in
      APL, and the miR-218/BMI-1 signaling axis may be a potential novel diagnostic
      marker and therapeutic target for the treatment of APL.

PMID- 29344252
TI  - iTRAQ-based quantitative proteomic analysis and bioinformatics study of proteins
      in retinoblastoma.
AB  - The aim of the present study was to analyze proteins in the aqueous humor (AH) of
      patients' retinoblastoma (RB), and investigate their potential role in RB using
      the comparative proteomic technique of isobaric tags for relative and absolute
      quantitation (iTRAQ) coupled with offline two-dimensional liquid chromatography
      tandem mass spectrometry. A total of 0.1 ml AH was collected from 10 children
      with RB (mean age, 3.8 years; range, 2-5 years) and patients with senile
      cataracts (mean age, 70.4 years; range, 65-79 years), which was used as the
      control. iTRAQ was used to analyze proteins in the AH of patients and controls.
      Proteins with a fold change of >1.20 or <0.83 were considered to be significantly
      differentially expressed (with corrected P<0.05). The identified proteins were
      subjected to subsequent gene ontology (GO) analysis using the DAVID database. A
      total of 83 proteins that were expressed differently between the controls and
      patients' AH samples were identified using iTRAQ analysis. Of these proteins, 44
      were upregulated and 39 were downregulated. On the basis of biological processes
      in GO, the identified proteins were primarily involved in glycoprotein, amyloid
      acute-inflammatory and defensive responses. Among these proteins, pigment
      epithelium-derived factor serves a potential role in the treatment of RB, and
      stimulated by retinoic acid 6 may serve as a potential protein involved in RB
      development. To the best of our knowledge, the present study is the first to
      identify 83 proteins associated with RB using iTRAQ technology. The results of
      the present study will aid in furthering the understanding of RB and developing
      novel therapy targets in the future.

PMID- 29344253
TI  - Diagnostic value of medical thoracoscopy in malignant pleural effusion induced by
      non-Hodgkin's lymphoma.
AB  - Malignant pleural effusion (MPE) appears in up to 20% of patients with non
      Hodgkin's lymphoma (NHL). The present study aimed to assess the efficacy of
      medical thoracoscopy (MT) in the diagnosis of patients with MPE induced by NHL.
      Between July 2005 and June 2014, 833 patients with pleural effusions of unknown
      etiology underwent MT in Beijing Chaoyang Hospital (Beijing, China), where
      diagnostic thoracocentesis or/and blind pleural biopsy had failed to yield an
      answer. Demographic, radiographic, thoracoscopic, histological and
      immunophenotyping data of 10 NHL patients with MPE were then retrospectively
      analyzed. Under medical thoracoscopy, pleural nodules (in n=6 patients),
      hyperemia (n=5), plaque-like lesions (n=4), pleural thickening (n=3), cellulose
      (n=3), ulcer (n=2), adhesion (n=2), and scattered hemorrhagic spots (n=1) were
      observed on the surface of parietal pleura. Histopathological and
      immunohistochemical analysis of pleural biopsy samples led to a correct diagnosis
      of B-cell NHL in 7 patients and T-lymphoblastic NHL in 2 patients. Data from the
      present study demonstrated that pleural biopsy through MT achieved a definite
      diagnosis of NHL in 9 out of 10 (90%) patients with MPE induced by NHL.
      Therefore, MT is a useful method for diagnosing MPE induced by NHL.

PMID- 29344254
TI  - Inhibitory effect of the low-toxic exogenous aryl hydrocarbon receptor modulator
      3'3-diindolylmethane on gastric cancer in mice.
AB  - 3'3-Diindolylmethane (DIM) has been proved to exhibit anticancer properties in
      many solid tumors. In our previous study, we demonstrated that DIM inhibited
      SGC7901 cell proliferation by inducing apoptosis and delaying cell cycle
      progression. Herein, we further explored the anti-tumor effect of DIM on SGC-7901
      tumor bearing mice. Tumors were excised, weighed, and tested by western blot and
      TdT-UTP nick-end labeling (TUNEL) assay. Blood samples were collected for
      biochemical analysis. The expression levels of AhR and cytochrome P450, family 1,
      subfamily A, polypeptide 1 (CYP1A1) protein were evaluated by western-blot assay.
      Our data show that with the increase of DIM dose (0, 5, 10, 20 mg/kg/day), AhR
      protein gradually decreased as CYP1A1 protein increased. The weight of the tumors
      found in the treated animals was significantly lower than that of the control
      group (0.845+/-0.096 vs. 1.275+/-0.236 g, 0.768+/-0.161 vs. 1.275+/-0.236 g,
      0.607+/-0.106 vs. 1.275+/-0.236 g, P<0.05). TUNEL test showed that DIM induced
      increased apoptosis in the treatment groups in a dose-dependent manner. Blood
      tests also indicated that DIM showed no toxic effect on animal weight or liver
      and kidney function. These results indicated that DIM agent could be a safe and
      potent drug in therapy of gastric cancer.

PMID- 29344255
TI  - Plasma olfactomedin 4 level in peripheral blood and its association with clinical
      features of breast cancer.
AB  - The present study aimed to investigate the expression of olfactomedin 4 (OLFM4)
      in plasma of patients with breast cancer and its association with diagnosis,
      metastasis and prognosis of breast cancer. OLFM4 gene expression level of
      peripheral blood plasma in 60 patients with breast cancer and 26 healthy donors
      was examined by ELISA. The expression of OLFM4 in tumor tissues of patients with
      breast cancer was evaluated by immunohistochemistry (protein expression) and
      reverse transcription-quantitative polymerase chain reaction (mRNA expression),
      respectively. Circulating tumor cells (CTCs) were detected in a certain set of
      patients. The expression of OLFM4 in plasma of the overall healthy people was
      higher compared with patients with breast cancer. The plasma OLFM4 level in
      patients with breast cancer was consistent with the expression of OLFM4 protein
      in tumor tissues (R2=1), indicating that the level of plasma OLFM4 expression may
      represent the expression of OLFM4 in breast cancer tissues. The plasma OLFM4
      level in patients with histological grade I was significantly lower compared with
      grade III (P<0.05). Breast cancer patients with positive CTC were associated with
      low level of plasma OLFM4. These results suggest that low OLFM4 expression in
      plasma or tissue specimens of breast cancer patients is more likely to represent
      low histological differentiation and decreased invasive/metastatic capabilities.
      Taken together, plasma OLFM4 level may be considered as a biomarker for diagnosis
      and prognosis of breast cancer for cases where there are difficulties in
      obtaining tumor tissue samples.

PMID- 29344256
TI  - Pien Tze Huang inhibits the growth of hepatocellular carcinoma cells by
      upregulating miR-16 expression.
AB  - Hepatocellular carcinoma (HCC) is characterized by uncontrolled proliferation and
      the deregulation of apoptotic signaling, although its molecular pathogenesis is
      not fully characterized. The ability to inhibit excessive proliferation and
      induce the apoptosis of cancer cells are crucial characteristics of anticancer
      drugs. Pien Tze Huang (PZH) is a widely used traditional Chinese medicine for the
      treatment of various types of cancer, and has exhibited promising therapeutic
      effects in clinical trials of HCC. However, the underlying mechanisms for its
      action are unclear. In the present study, the aim was to explore the effect of
      PZH on the proliferation and apoptosis of the BEL-7402 HCC cell line, and the
      associated mechanisms. PZH treatment significantly inhibited BEL-7402 cell
      viability, confluence and clonogenicity, inducing cell cycle arrest and promoting
      apoptosis. In addition, PZH treatment suppressed the expression of the pro
      proliferative genes cyclin D1 and cyclin-dependent kinase 4, and decreased the
      expression of the anti-apoptotic gene Bcl-2. PZH treatment also upregulated the
      expression of a key microRNA (miR), miR-16. The study demonstrated that PZH can
      effectively inhibit cancer cell proliferation and induce apoptosis in BEL-7402
      HCC cells via the upregulation of the tumor suppressor miR-16.

PMID- 29344257
TI  - Involvement of soluble B7-H3 in combination with the serum inflammatory cytokines
      interleukin-17, -8 and -6 in the diagnosis of hepatocellular carcinoma.
AB  - Previous studies have demonstrated that B7-H3, and the inflammatory cytokines
      interleukin (IL)-17, IL-8 and IL-6, are involved in the development of a variety
      of tumors. The objectives of the present study were: i) To investigate the
      association between soluble B7-H3 (sB7-H3) and cytokine levels of IL-17, IL-8 and
      IL-6 in the serum of patients with hepatocellular carcinoma (HCC); and ii) to
      determine their potential value for use in HCC diagnosis. Serum sB7-H3, IL-17, IL
      8 and IL-6 levels in the HCC patients and healthy control subjects were measured
      using ELISA. The accuracy of each of these biomarkers in HCC diagnosis was
      compared using a receiver operating characteristic curve and the area under the
      curve (AUC). A logistic regression model was used to investigate the accuracy of
      diagnosing HCC when evaluated using combined determinations of sB7-H3, IL-17, IL
      8 and IL-6 levels. The data demonstrated that serum levels of sB7-H3, IL-17, IL-8
      and IL-6 were significantly increased in HCC patients compared with those in the
      healthy control group. Serum sB7-H3 levels were positively associated with serum
      IL-17, whereas serum IL-8 levels were negatively correlated with serum IL-17
      levels. The AUC values for sB7-H3, IL-17, IL-8 and IL-6 were 83.2, 65.7, 95.3 and
      97.0%, respectively, and indicated that all four biomarkers exhibited a
      statistically significant capacity for diagnosing HCC. Using the logistic
      regression model, the AUC value, sensitivity and specificity, as determined for
      the combination of the four biomarkers, were 99.2, 96.67 and 97.14%,
      respectively. This was significantly greater than that achieved when any single
      biomarker was used alone in the logistic regression model to assess their
      accuracy in HCC diagnosis. The optimum cutoff value of the predicted probability
      obtained by the combination of sB7-H3, IL-17, IL-8 and IL-6 in the regression
      model was 0.5745. To conclude, the present study revealed that there exists a
      positive association between serum sB7-H3 and IL-17 levels in HCC patients.
      Determinations involving the combination of serum sB7-H3, IL-17, IL-8 and IL-6
      levels demonstrate great potential for use in HCC diagnosis.

PMID- 29344258
TI  - Involvement of breast cancer stem cells in tumor angiogenesis.
AB  - The aim of the present study was to investigate the role of breast cancer stem
      cells (BCSCs) in the angiogenesis of breast cancer tumors. The expression levels
      of mutant p53, cluster of differentiation (CD)31, vascular endothelial factor
      (VEGF), in addition to human epidermal growth factor (HER)2, were detected in the
      blood vessels of human breast cancer (BC) tissue samples. CD44+/CD24-/low cells
      were selected from single-cell suspensions of BC tissues to assess the expression
      of CD31 and CD105, in addition to the ability of these cells to metabolize
      acetylated low-density lipoprotein (Ac-LDL). Furthermore, vascular-like
      structures were observed histologically. Mutant p53, CD31 and VEGF were all
      expressed in these tissues. CD44+ cells comprised 7.5+/-2.6 and 94.3+/-4.7% of
      the cell population prior to and following sorting, respectively. CD24+ cells
      comprised 48.2+/-9.4 and 4.3+/-4% of the cell population prior to and following
      sorting, respectively. A low proportion of CD24+ cells corresponded to a high
      proportion of CD24-/low cells. The percentages of CD105+ and CD31+ glomus cells
      in the mammary gland were 4.5+/-0.9 and 6.2+/-1.3%, respectively, and following
      passaging for three generations, these increased to 79.6+/-9.3 and 84.1+/-10.7%,
      respectively (P<0.05). Cells were cultured using an endothelial cell culture
      system, and they internalized DiL-Ac-LDL. Here, vascular endothelial cells formed
      vascular-like structures, whereas the control group demonstrated no such
      structures. Overall, the results suggest that BCSCs-derived endothelial cells may
      contribute to tumor angiogenesis.

PMID- 29344259
TI  - Lesions of the central nervous system in leukemia: Pathological and magnetic
      resonance imaging features at presentation in 14 patients.
AB  - The present study aimed to characterize the specific pathology and magnetic
      resonance imaging (MRI) findings observed in patients with leukemia with central
      nervous system (CNS) lesions, and to determine their value in the management of
      such patients. Lesions of the CNS were observed during and following treatment of
      leukemia. The data from stereotactic biopsy-proven pathology (12 patients) and
      MRI examinations (14 patients) were retrospectively evaluated. Proton-magnetic
      resonance-spectroscopy was performed in three patients. Factors that predisposed
      to lesions of the CNS were reviewed from the patient medical records. Among the
      14 patients, eight had CNS leukemia, four had a CNS infection and two had a
      neurodegenerative disorder (one leukoencephalopathy and one glial cell
      hyperplasia). The clinical diagnosis based on clinical symptoms, signs and MRI
      features was not consistent with the pathological diagnosis in two patients. In
      one patient, the clinical diagnosis was a CNS infection; however, the patient's
      pathological diagnosis was CNS leukemia. In the other patient, the clinical
      diagnosis was CNS leukemia, but the pathological diagnosis was glial cell
      hyperplasia. CNS lesions in leukemia have a wide range of causes. Apart from the
      relapse of leukemia in the CNS, there are treatment-associated neurotoxicities
      and infections that are caused by immunocompromised states. As numerous leukemia
      associated CNS lesions are treatable, early diagnosis is essential.

PMID- 29344260
TI  - DR2 blocker thioridazine: A promising drug for ovarian cancer therapy.
AB  - Dopamine receptor 2 (DR2) may be a biomarker for various types of cancer. Ovarian
      cancer cells overexpress DR2; therefore, blocking DR2 may be a novel treatment
      strategy for ovarian cancer. Thioridazine, a DR2 blocker, has antineoplastic
      activity in a variety of cancer cells. In view of the requirement for novel
      therapeutic agents in ovarian cancer, the present study aimed to determine the
      potential effects of thioridazine in vitro and in vivo. It was revealed that the
      DR2 blocker thioridazine induced cell death in a dose-dependent manner in ovarian
      cancer cells. Thioridazine treatment induced apoptosis and autophagy, which may
      be attributed to an increased level of reactive oxygen species and associated DNA
      damage. Additionally, the expression of various proteins increased with oxidative
      stress, including nuclear factor E2-related factor 2, which is a pivotal
      transcriptional factor involved in cellular responses to oxidative stress. Heme
      oxygenase 1, NAPDH quinone dehydrogenase 1 and hypoxia inducible factor-1alpha
      and phosphorylated (p)-protein kinase B expression was significantly decreased,
      and the expression level of p-extracellular signal-related kinases and p-P38 was
      increased. Using 3-methyl adenine to inhibit autophagy caused the rate of
      apoptosis to increase. Thioridazine inhibited the growth of SKOV3 xenografts in
      nude mice. The present study demonstrated that the DR2 blocker thioridazine
      exhibited anticancer effects in vitro and in vivo, suggesting that thioridazine
      may be used as a potential drug in ovarian cancer therapy.

PMID- 29344261
TI  - T cell acute lymphoblastic lymphoma complicated with myeloid sarcoma in an adult:
      A case report.
AB  - The present case report describes a rare case of T cell acute lymphoblastic
      lymphoma (T-LBL) in the lymph node with myeloid sarcoma in the pericardium. A 33
      year-old Chinese male was admitted to hospital on 4 July 2015 exhibiting a fever
      and having experienced wheezing and fatigue for the previous 7 days. Routine
      pathological, computed tomographic, cytological and immunophenotypic observations
      revealed a diagnosis of T-LBL in the lymph node on 7 August 2015, without
      evidence of bone marrow (BM) involvement. The patient received induction
      chemotherapy for T-LBL and achieved partial remission. The patient was identified
      to have multiple serous effusion and analysis of pericardial effusion cells
      revealed the diagnosis of T-LBL with extramedullary myeloid sarcoma (without BM
      involvement) on 25 November 2015. On 30 December 2015, the patient was identified
      to exhibit proliferation of primary myeloid cells in the peripheral blood and BM,
      and an abnormal karyotype in BM cells, indicating that the complicated myeloid
      sarcoma involved the BM. No matched donor was available so the patient received
      chemotherapy to manage the disease. The patient was discharged on 31 January 2016
      and ceased treatment. The patient succumbed on 19 February 2016 at home. To the
      best of our knowledge, T-LBL complicated with myeloid sarcoma had not been
      previously reported in Chinese adult male patients. In addition, the involvement
      of the BM and aberrant karyotype of the complicated myeloid sarcoma in the
      patient were rare.

PMID- 29344262
TI  - Hedyotis diffusa willd extract suppresses colorectal cancer growth through
      multiple cellular pathways.
AB  - The development of colorectal cancer (CRC) is strongly associated with the
      imbalance of various intracellular signal transduction cascades, including
      protein kinase B (AKT), mitogen-activated protein kinase 1 (MAPK), signal
      transducer and activator of transcription 3 (STAT3), as well as crosstalk between
      these signaling networks. At present, anti-tumor agents are often single-targeted
      and therefore are not always therapeutically effective. Moreover, long-term use
      of these anti-tumor agents often generates drug resistance and potential side
      effects. These problems highlight the urgent need for the development of novel
      and more effective anti-cancer drugs. Hedyotis diffusa Willd (HDW) has been used
      as a major component in traditional Chinese medicine for the clinical treatment
      of colorectal cancer, with a limited number of adverse effects. However, the
      molecular mechanisms, which underlie its anti-cancer activity, still require
      further elucidation. In the present study, using xenograft models and various
      different human CRC cell lines, the efficacy of the ethanol extract of HDW
      (EEHDW) against tumor growth was evaluated, and its underlying molecular
      mechanisms of action were investigated. It was demonstrated that EEHDW was able
      to inhibit cancer growth in vivo and in vitro. Furthermore, EEHDW was able to
      suppress the activation of several CRC-associated signaling pathways and was able
      to regulate the expression of various inflammatory and angiogenic factors. This
      resulted in the induction of apoptosis and inhibition of cellular proliferation,
      as well as tumor angiogenesis. The present study demonstrated that EEHDW is able
      to exhibit anti-cancer activity due to its ability to affect multiple
      intracellular targets, which suggests that it may be a novel multi-potent
      therapeutic agent for the treatment of colorectal cancer.

PMID- 29344263
TI  - Thalidomide inhibits proliferation and epithelial-mesenchymal transition by
      modulating CD133 expression in pancreatic cancer cells.
AB  - Pancreatic cancer is a solid malignancy with a high mortality rate, on account of
      the high incidence of metastasis at the time of detection. The aggressiveness of
      pancreatic cancer may be partly driven by cancer stem cells (CSCs), which are
      characterized by the ability to self-renew and recapitulate tumors in the ectopic
      setting. However, although a number of drugs targeting CSCs are currently under
      clinical investigation, few effective drugs have been developed. The present
      study demonstrated that thalidomide inhibited cell proliferation and metastasis
      in pancreatic cancer cell lines through the inhibition of epithelial mesenchymal
      transition. The effect of thalidomide was more pronounced in cluster of
      differentiation 133 (CD133)+ SW1990 cells than in Capan-2 cells, in which CD133
      expression was almost undetectable. The results revealed that CD133 is likely to
      serve a role in the antitumor effect of thalidomide and indicated that
      thalidomide could be developed as a CSC-specific adjuvant chemotherapy in
      pancreatic cancer.

PMID- 29344264
TI  - Preclinical and clinical implications of TERT promoter mutation in glioblastoma
      multiforme.
AB  - The promoter region of the telomerase reverse transcriptase gene (TERT) is
      mutated in a subpopulation of patients with glioblastoma multiforme (GBM). In the
      present study, preclinical and clinical implications of the mutation were
      analyzed in 25 GBMs to evaluate its utility as a therapeutic target. Associations
      between the TERT promoter mutation and a number of preclinical/clinical
      characteristics were analyzed. Notably, the TERT promoter mutation was identified
      in 92.3% of GBMs where dissociated cells revealed in vitro sphere formation
      capacity; while the TERT promoter mutation was identified in 33.3% of GBMs
      without in vitro sphere formation capacity (P=0.004). In addition, this
      significantly increased mutation rate was observed in GBMs with in vivo
      tumorigenic potential (80% vs. 0%; P=0.004). Furthermore, patients with GBM
      exhibiting the TERT promoter mutation demonstrated significantly decreased
      overall survival rate compared with patients lacking this mutation (81.7 vs.
      152.6 weeks; P=0.026). The results of the present study indicated that the TERT
      promoter mutation is associated with the self-renewal capacity of GBM cells and
      clinical aggressiveness of GBMs, which may be translated to a targeting therapy
      against TERT to inhibit the self-renewal of GBM cells.

PMID- 29344265
TI  - High expression of PU.1 is associated with Her-2 and shorter survival in patients
      with breast cancer.
AB  - The transcription factor PU.1 was previously identified as an oncogene or a tumor
      suppressor in different types of leukemia. The aim of the present study was to
      investigate the expression of PU.1 in breast cancer and to analyze its
      association with clinical features and prognosis. Immunohistochemistry was used
      to determine PU.1 expression in breast cancer tissue microarrays and paraffin
      embedded sections. The association between PU.1 expression and
      clinicopathological factors was assessed by using chi-square test. The survival
      analysis of patients was conducted by using Kaplan-Meier analysis and log-rank
      tests. Cox regression was utilized for univariate and multivariate analyses of
      prognostic factors. The results indicated that the expression level of PU.1
      protein in breast cancer samples was significantly higher compared with normal
      breast tissues (P=2.63*10-8). Furthermore, the level of PU.1 expression was
      detected to be positively associated with androgen receptor (P=0.027) and human
      epidermal growth factor receptor 2 status (P=2.03*10-21) as well as molecular
      subtype (P=3.51*10-11). Furthermore, patients with negative PU.1 expression had
      longer OR compared with those with positive PU.1 expression (P=3.67*10-4).
      Multivariate Cox regression analysis revealed that PU.1 expression level and
      tumor-node-metastasis stage were independent prognostic factors for overall
      survival (P=0.034 and P=0.018, respectively). Therefore, PU.1 protein expression
      may contribute to breast cancer progression and may be a valuable molecular
      marker to predict the prognosis of patients with breast cancer.

PMID- 29344266
TI  - Erratum: HBV suppresses thapsigargin-induced apoptosis via inhibiting CHOP
      expression in hepatocellular carcinoma cells.
AB  - [This corrects the article DOI: 10.3892/ol.2017.6666.].

PMID- 29344268
TI  - Interferon-gamma and Colorectal Cancer: an up-to date.
AB  - Colorectal cancer still remains the third cause of cancer death among cancer
      patients. Early diagnosis is crucial and they can be either endoscopic or with
      blood biomarkers. Endoscopic methods consist of gastroscopy and colonoscopy,
      however; in recent years, endoscopic ultrasound is being used. The
      microenvironment is very important for the successful delivery of the treatment.
      Several proteins and hormones play a crucial role in the efficiency of the
      treatment. In the current mini review we will focus on interferon-gamma.

PMID- 29344270
TI  - Lenvatinib in Advanced Radioiodine-Refractory Thyroid Cancer - A Retrospective
      Analysis of the Swiss Lenvatinib Named Patient Program.
AB  - Purpose: Differentiated thyroid cancer (DTC) accounts for approximately 95% of
      thyroid carcinomas. In the metastatic RAI-refractory disease, chemotherapy has
      very limited efficacy and is associated with substantial toxicity. With
      increasing knowledge of the molecular pathogenesis of DTC, novel targeted
      therapies have been developed. Lenvatinib is a tyrosine kinase inhibitor (TKI)
      with promising clinical activity based on the randomized phase III SELECT trial.
      In Switzerland, a Named Patient Program (NPP) was installed to bridge the time
      gap to Swissmedic approval. Here, we report the results from the Swiss Lenvatinib
      NPP including patients with metastatic RAI-refractory DTC. Methods: Main
      inclusion criteria for the Swiss NPP were RAI-refractory DTC, documented disease
      progression, Eastern Cooperative Oncology Group (ECOG) performance status 0-3.
      The number of previous therapies was not limited. The Swiss Lenvatinib NPP was
      initiated in June 2014 and was closed in October 2015 with the approval of the
      drug. Results: Between June 2014 and October 2015, 13 patients with a median age
      of 72 years have been enrolled. Most patients (69%) had at least one prior
      systemic therapy, mainly sorafenib. 31% of patients showed a PR and 31% SD.
      Median progression free survival was 7.2 months and the median overall survival
      was 22.7 months. Dose reduction due to adverse events was necessary in 7 patients
      (53%). At the time of analysis 6 patients (47%) were still on treatment with a
      median time on treatment of 9.98 months. Conclusions: Our results show that
      lenvatinib has reasonable clinical activity in unselected patients with RAI
      refractory thyroid cancer with nearly two-third of patients showing clinical
      benefit. The toxicity profile of lenvatinib is manageable.

PMID- 29344267
TI  - Break Breast Cancer Addiction by CRISPR/Cas9 Genome Editing.
AB  - Breast cancer is the leading diagnosed cancer for women globally. Evolution of
      breast cancer in tumorigenesis, metastasis and treatment resistance appears to be
      driven by the aberrant gene expression and protein degradation encoded by the
      cancer genomes. The uncontrolled cancer growth relies on these cellular events,
      thus constituting the cancerous programs and rendering the addiction towards
      them. These programs are likely the potential anticancer biomarkers for
      Personalized Medicine of breast cancer. This review intends to delineate the
      impact of the CRSPR/Cas-mediated genome editing in identification and validation
      of these anticancer biomarkers. It reviews the progress in three aspects of
      CRISPR/Cas9-mediated editing of the breast cancer genomes: Somatic genome
      editing, transcription and protein degradation addictions.

PMID- 29344269
TI  - Early and Partial Reduction in CD4+Foxp3+ Regulatory T Cells during Colitis
      Associated Colon Cancer Induces CD4+ and CD8+ T Cell Activation Inhibiting
      Tumorigenesis.
AB  - Colorectal cancer (CRC) is the second most commonly diagnosed cancer in women and
      the third in men in North America and Europe. CRC is associated with inflammatory
      responses in which intestinal pathology is caused by different cell populations
      including a T cell dysregulation that concludes in an imbalance between activated
      T (Tact) and regulatory T (Treg) cells. Treg cells are CD4+Foxp3+ cells that
      actively suppress pathological and physiological immune responses, contributing
      to the maintenance of immune homeostasis. A tumor-promoting function for Treg
      cells has been suggested in CRC, but the kinetics of Treg cells during CRC
      development are poorly known. Therefore, using a mouse model of colitis
      associated colon cancer (CAC) induced by azoxymethane and dextran sodium sulfate,
      we observed the dynamic and differential kinetics of Treg cells in blood, spleen
      and mesenteric lymph nodes (MLNs) as CAC progresses, highlighting a significant
      reduction in Treg cells in blood and spleen during early CAC development, whereas
      increasing percentages of Treg cells were detected in late stages in MLNs.
      Interestingly, when Treg cells were decreased, Tact cells were increased and vice
      versa. Treg cells from late stages of CAC displayed an activated phenotype by
      expressing PD1, CD127 and Tim-3, suggesting an increased suppressive capacity.
      Suppression assays showed that T-CD4+ and T-CD8+ cells were suppressed more
      efficiently by MLN Treg cells from CAC animals. Finally, an antibody-mediated
      reduction in Treg cells during early CAC development resulted in a better
      prognostic value, because animals showed a reduction in tumor progression
      associated with an increased percentage of activated CD4+CD25+Foxp3- and
      CD8+CD25+ T cells in MLNs, suggesting that Treg cells suppress T cell activation
      at early steps during CAC development.

PMID- 29344271
TI  - Clinical-pathological Characteristics and Prognostic Factors for Papillary
      Thyroid Microcarcinoma in the Elderly.
AB  - Background: The incidence of papillary thyroid microcarcinoma (PTMC) has
      increased dramatically over the past three decades worldwide. The annual rate of
      increase in the elderly (>=65) PTMC patients is 1.4 times higher than that in the
      adult (<65) PTMC patients. The aim of the present study is to identify the
      clinical-pathological characteristics and prognostic factors in the elderly PTMC
      patients. Methods: The source population is PTMC patients whose information is
      available in the Surveillance, Epidemiology and End Results (SEER) database (2004
      2013). We analyzed specific selected clinical-pathological parameters and
      prognostic factors for the PTMC patients who were aged 65 or above (N=4812).
      Results: Within the elderly group, the male patients, in comparison to the
      females, had a higher percentage of lymph-node metastases (5.29% vs. 12.27%, P <
      0.001), distant metastasis (0.27% vs. 1.07%, P < 0.001), and stage III-IV tumors
      (9.19% vs. 15.85%, P < 0.001). Moreover, the elderly patients had a lower median
      cause-specific survival (CSS) compared with the adult patients (P < 0.001). Stage
      III-IV disease (hazard ratio (HR): 8.064, P < 0.001) was a strong risk factor for
      PTMC CSS. Being female (HR: 0.440, P = 0.011), total thyroidectomy (HR: 0.057, P
      = 0.001), and lobectomy (HR: 0.058, P < 0.001) were all strong protectors of PTMC
      CSS. Conclusion: Thyroidectomy improved CSS of the elderly PTMC patients.
      Compared with thyroid lobectomy, total thyroidectomy did not increase CSS for the
      elderly PTMC patients. The elderly PTMC patients who received radio therapy did
      not experience an increase in CSS.

PMID- 29344272
TI  - Cancer vaccine: learning lessons from immune checkpoint inhibitors.
AB  - Cancer vaccines have been exclusively studied all through the past decades, and
      have made exceptional achievements in cancer treatment. Few cancer vaccines have
      been approved by the US Food and Drug Administration (FDA), for instance,
      Provenge, which was approved for the treatment of prostate carcinoma in 2012.
      Moreover, more recently, T-VEC got approval for the treatment of melanoma. While,
      the overall therapeutic effects of cancer vaccines have been taken into
      consideration as below expectations, low antigenicity of targeting antigen and
      tumor heterogeneity are the two key limiting barriers encountered by the cancer
      vaccines. Nonetheless, recent developments in cancer immune-therapies together
      with associated technologies, for instance the unparalleled achievements bagged
      by immune checkpoint inhibitor based therapies and neo-antigen identification
      tools, envisage potential improvements in cancer vaccines in respect to the
      treatments of malignancies. This review brings forth measures for the purpose of
      refining therapeutic cancer vaccines by learning lessons from the success of PD-1
      inhibitor based immune-therapies.

PMID- 29344273
TI  - A single nucleotide polymorphism in CYP1B1 leads to differential prostate cancer
      risk and telomere length.
AB  - BACKGROUND: Cytochrome P450 1B1 (CYP1B1) is a key enzyme in its oestrogen
      metabolism pathway, giving rise to hydroxylation and conjugation. Functionally
      relevant genetic variants within CYP1B1 may affect the telomere length and
      subsequently lead to prostate carcinogenesis. METHODS: We evaluated 8 CYP1B1 tag
      single nucleotide polymorphisms (SNPs) in 1015 men with prostate cancer (PCa) and
      1052 cancer-free controls, and calculated odds ratios (ORs) and 95% confidence
      intervals (CIs) to estimate their association with risk of PCa. The influence of
      CYP1B1 SNPs on the relative telomere lengths was then appraised in peripheral
      blood leukocytes using real-time PCR. RESULTS:CYP1B1 rs1056836 variant was
      associated with decreased risk of PCa [odds ratio (OR): 0.80; 95% confidence
      interval (CI): 0.68-0.99, P = 0.041]. Longer telomere length showed a
      significantly higher proportion of the CYP1B1 rs1056836 CG/GG genotypes, compared
      with that of the CC genotype (OR: 1.60, 95% CI: 1.04-2.45). CONCLUSION: Our
      findings suggest that genetic variants within CYP1B1 may confer genetic
      susceptibility to PCa by altering telomere length.

PMID- 29344274
TI  - Immunotherapy of patient with hepatocellular carcinoma using cytotoxic T
      lymphocytes ex vivo activated with tumor antigen-pulsed dendritic cells.
AB  - Purpose The aim of this study was to evaluate the clinical response of
      immunotherapy with dendritic cell-cytotoxic T lymphocytes (DC-CTLs) in patients
      with hepatocellular carcinoma (HCC). Method Sixty-eight patients with a confirmed
      diagnosis of HCC and who received follow-up until December 2015 were enrolled. We
      measured immune phenotypes of DCs and activated T cells using flow cytometry and
      clinical indexes using an electrochemiluminescence method. Results DCs exhibited
      up-regulation of the maturation markers CD83, CD80, CD11c, and CD86 on day8.
      Levels of IFN-gamma and TNF-alpha were higher in the DCs pulsed with tumor
      associated antigens (TAAs) than in DCs with a non-proliferative recombinant
      adenovirus. The percentage of regulatory T cells (Tregs) decreased in patients
      after DC-CTLs therapy. In addition, serum levels of AFP, AFP-L3, ALT, and CA19-9
      were significantly reduced in these patients. Quality of life was improved,
      especially on physical functioning scales. Median overall survival (OS) and
      progression-free survival (PFS) were 8.2 months and 4.3 months, respectively, for
      the control group and 12.8 months and 9 months, respectively, for the DC-CTL
      group. Patients treated with DC-CTLs therapy showed a statistically significant
      PFS and OS curve (OS: p=0.016; PFS: p<0.0001). In addition, no serious adverse
      reactions were observed. Conclusion This study indicated that Tregs, as well as
      serum levels of AFP, AFP-L3, ALT, and CA19-9, which were correlated with a poor
      prognosis, decreased after DC-CTL treatments. The OS, PFS and the quality of life
      of HCC patients partially improved.

PMID- 29344275
TI  - Genistein Promotes Proliferation of Human Cervical Cancer Cells Through Estrogen
      Receptor-Mediated PI3K/Akt-NF-kappaB Pathway.
AB  - Phytoestrogens are polyphenol compounds which have similar structure to 17beta
      estradiol (E2), a kind of main estrogen in women. Thus, phytoestrogens may affect
      the reproductive and endocrine systems, leading to the development of estrogen
      related cancers. The effect of genistein (Gen), one of the most studied
      phytoestrogens, on human cervical cancer cells (HeLa) was investigated in this
      study. It was found that Gen at concentrations of 0.001, 0.01, 0.1 and 1 umol.L-1
      promoted the proliferation of HeLa cells in a dose-dependent manner. Gen
      increased the portion of HeLa cells in S phase and decreased the portion of the
      cells in G1 phase. Besides, apoptosis rate of the cells was significantly lower
      when treated with Gen compared with the control group. It was also found that the
      expression of ERalpha, Akt or nuclear NF-kappaB p65 protein was activated by Gen.
      The correlation between these three proteins may be as following: ERalpha was the
      upstream, followed by Akt, and then nuclear NF-kappaB p65 protein. In addition,
      the downstream genes of activated nuclear NF-kappaB p65 were found to be
      associated with cell cycle and apoptosis of cancer cells. Our results suggested
      that Gen may stimulate cell proliferation partially through the estrogen receptor
      mediated PI3K/Akt-NF-kappaB pathway and the further activation of the downstream
      genes of nuclear NF-kappaB p65.

PMID- 29344276
TI  - The Clinicopathological Features and Survival Outcomes of Different Histological
      Subtypes in Triple-negative Breast Cancer.
AB  - Purpose: To determine the clinicopathological features and survival outcomes of
      triple-negative breast cancer (TNBC) according to different histological
      subtypes. Methods: Using the Surveillance, Epidemiology, and End Results
      database, we included TNBC cases in 2010-2013. The effect of histological subtype
      on breast cancer-specific survival (BCSS) and overall survival (OS) were analyzed
      using univariate and multivariate analyses. Results: A total of 19,900 patients
      were identified. Infiltrating ductal carcinoma not otherwise specified accounted
      for 91.6% of patients, followed by metaplastic carcinoma (2.7%), medullary
      carcinoma (1.4%), mixed lobular-ductal carcinoma (1.4%), lobular carcinoma
      (1.3%), apocrine carcinoma (1.0%), and adenoid cystic carcinoma (0.6%). Medullary
      carcinoma was more frequently poorly/undifferentiated. Significantly more lobular
      carcinoma, mixed lobular-ductal carcinoma, and metaplastic carcinoma patients had
      larger tumors. Adenoid cystic carcinoma, metaplastic carcinoma, medullary
      carcinoma, and apocrine carcinoma were more frequently node-negative. Lobular
      carcinoma (16.0%) and mixed lobular-ductal carcinoma (10.4%) more frequently had
      distant stage at initial diagnosis. Histologic subtype was an independent
      prognostic factor of BCSS and OS. Compared with infiltrating ductal carcinoma,
      medullary carcinoma and apocrine carcinoma had better BCSS and OS, while mixed
      lobular-ductal carcinoma and metaplastic carcinoma had worse survival. Adenoid
      cystic carcinoma survival was not significantly different from that of
      infiltrating ductal carcinoma. Conclusions: TNBC histological subtypes have
      different clinicopathological characteristics and survival outcomes. Medullary
      carcinoma and apocrine adenocarcinoma have excellent prognosis; mixed lobular
      ductal carcinoma and metaplastic carcinoma are the most aggressive subtypes.

PMID- 29344277
TI  - Capn4 overexpression indicates poor prognosis of ovarian cancer patients.
AB  - Recent studies have shown a close correlation between Capn4 expression and the
      prognosis of patients with solid tumors. This study aimed to investigate clinical
      role of Capn4 in ovarian cancer. The expression of Capn4 in 113 ovarian cancer
      and 35 non-tumor tissue samples were detected by quantitative real-time
      polymerase chain reaction (qRT-PCR). Capn4 expression was significantly
      upregulated in ovarian cancer tissues compared with non-tumor tissues (p < 0.01),
      and was positively correlated to FIGO stage, tumor grade and distant metastasis
      of ovarian cancer. Kaplan-Meier analysis indicated that patients with high Capn4
      expression had shorter overall survival (HR = 1.929, 95%CI: 1.210-3.077, P=
      0.006) and progress-free survival (PFS) (HR = 2.043, 95%CI: 1.276-3.271, P=
      0.003). Moreover, univariate Cox regression analysis demonstrated that Capn4
      overexpression was an unfavorable prognostic factor for ovarian cancer (HR =
      2.819, 95%CI: 1.365-3.645, P = 0.003). After the adjustment with age,
      histological type and tumor size, multivariate Cox regression analysis showed
      that Capn4 expression level (HR = 2.157,95%CI: 1.091-3.138, P = 0.014), distant
      metastasis (HR = 1.576, 95%CI: 1.025-3.012, P = 0.028), tumor grade (HR = 1.408,
      95%CI: 0.687-2.884, P = 0.037), and FIGO stage (HR = 1.791, 95%CI: 1.016-3.158,
      P=0.036) were independent poor prognostic indicators for ovarian cancer. In
      conclusion, Capn4 has the potential as a new prognostic marker for patients with
      ovarian cancer.

PMID- 29344278
TI  - Potent peptide-conjugated silicon phthalocyanines for tumor photodynamic therapy.
AB  - Phthalocyanines (Pcs) are a group of promising photosensitizers for use in
      photodynamic therapy (PDT). However, their extremely low solubility and their
      strong tendency to aggregate in aqueous solution greatly restrict their
      application. Conjugation of Pc macrocycles with peptide ligands could be a very
      useful strategy to optimize the physical properties of Pcs not only by increasing
      their water solubility and reducing their aggregation but also by endowing the
      conjugates with a tumor-targeting capability. To develop highly potent
      photosensitizers for tumor PDT, we prepared new peptide-conjugated
      photosensitizers using silicon Pc (SiPc), which has much higher photodynamic
      activity than zinc Pcs, as the light activation moiety and the cRGDfK peptide (or
      simply cRGD) as the peptide moiety. A polyethylene glycol linker and an extra
      carboxylic acid group were also tested for introduction into the conjugates to
      optimize the conjugate structure. The conjugates' photophysical and photodynamic
      behaviors were then carefully evaluated and compared using in vitro and in vivo
      experiments. One of the prepared conjugates, RGD-(Linker)2-Glu-SiPc, showed
      excellent physical properties and photodynamic activity, with an EC50 (half
      maximal effective concentration) of 10-20 nM toward various cancer cells. This
      conjugate eradicated human glioblastoma U87-MG tumors in a xenograft murine tumor
      model after only one dose of photodynamic treatment, with no tumor regrowth
      during observation for up to 35 days. The conjugate RGD-(Linker)2-Glu-SiPc thus
      showed highly promising potential for use in tumor treatment.

PMID- 29344279
TI  - Positive Expression of SMYD2 is Associated with Poor Prognosis in Patients with
      Primary Hepatocellular Carcinoma.
AB  - Purpose: SET and MYND domain-containing protein2 (SMYD2), a histone lysine
      methyltransferases, is a candidate human oncogene in multiple tumors. However,
      the expression dynamics of SMYD2 in hepatocellular carcinoma (HCC) and its
      clinical/prognostic significance are unclear. Methods: The SMYD2 expression
      profile was examined by quantitative real-time polymerase chain reaction (qRT
      PCR), and immunohistochemistry (IHC) in HCC tissues and matched adjacent non
      tumorous tissues. SMYD2 was silenced in HCC cell lines to determine its role in
      tumor proliferation and cell cycle progression, and the possible mechanism.
      Spearman's rank correlation, Kaplan-Meier plots and Cox proportional hazards
      regression model were used to analyze the data. Results: The SMYD2 expression in
      HCC tissues were significantly up-regulated at both mRNA and protein levels as
      compared with the matched adjacent non-tumorous tissues. By IHC, positive
      expression of SMYD2 was examined in 122/163 (74.85%) of HCC and in 10/59 (16.95%)
      of tumor-adjacent tissues. Positive expression of SMYD2 was correlated with tumor
      size, vascular invasion, differentiation and TNM stage (P < 0.05). In univariate
      survival analysis, a significant association between positive expression of SMYD2
      and shortened patients' survival was found (P < 0.05). Importantly, SMYD2
      expression together with vascular invasion (P < 0.05) provided significant
      independent prognostic parameters in multivariate analysis. Functionally, SMYD2
      silenced markedly inhibited cell proliferation and cell cycle progression in SMMC
      7721 cell. Conclusions: Our findings provide evidences that positive expression
      of SMYD2 in HCC may be important in the acquisition of an aggressive phenotype,
      and it is an independent biomarker for poor prognosis of patients with HCC.

PMID- 29344280
TI  - MiR-378 and MiR-1827 Regulate Tumor Invasion, Migration and Angiogenesis in Human
      Lung Adenocarcinoma by Targeting RBX1 and CRKL, Respectively.
AB  - MicroRNAs (miRNAs) have been extensively studied over the decades and have been
      proposed as potential molecular targets for cancer treatment. Studies have shown
      that miR-378 participates in numerous biological processes in various cancers;
      whereas miR-1827 has only been reported in pediatric glioma. The mechanism of how
      miRNAs modulate lung cancer metastasis remains unclear. Our previous study
      demonstrated that miR-378 is up-regulated while miR-1827 is down-regulated in
      high invasive lung cancer sub-cell lines, and their biological functions have
      been described. Here, we report that miR-378 and miR-1827 modulate lung cancer
      cell invasion and migration via epithelial-mesenchymal transition (EMT). We also
      demonstrated that cells treated with miR-378 inhibitors or miR-1827 mimics had
      reduced number of metastases and ectopic vessels in the zebrafish embryo model.
      We then showed that miR-378 promoted invasion and miR-1827 suppressed migration
      by targeting RBX1 and CRKL, respectively. Restored protein expression in miRNA
      overexpressed/ miRNA-suppressed cells attenuated the inhibitory/ inducing effect
      of the miRNA on lung cancer cells. Collectively, our findings highlight that miR
      378 and miR-1827 could serve as novel therapeutic targets in lung cancer.

PMID- 29344281
TI  - Keratin17 Promotes Tumor Growth and is Associated with Poor Prognosis in Gastric
      Cancer.
AB  - Krt17 is a 48kDa protein member of keratin family. Previous literatures have
      demonstrated Krt17 may play a promotive role in the progression of various
      malignancies. However, the exact function of Krt17 in the carcinogenesis and the
      progression of gastric cancer (GC) remains unknown. In the present study, the
      expression of Krt17 in 20 fresh GC and matched normal tissues were detected and
      Krt17 was found to be significantly increased in GC tissues compared to normal
      tissues. And then the immunochemistry was performed to investigate the Krt17
      expression in 569 GC tissue specimens, we found that the expression of Krt17 was
      remarkably positively correlated with the tumor size (P < 0.01), depth of
      invasion (T) (P < 0.001), lymph node metastasis (N) (P < 0.001), tumor node
      metastasis (TNM) stage (P < 0.001) and vascular invasion (P < 0.05). High
      expression of Krt17 predicted a poor prognosis of GC patients. In addition, we
      showed silencing of Krt17 inhibited GC cell proliferation, migration and
      invasion, and induced cell apoptosis by altering Bcl2 family protein expression
      and cleaved caspase3 upregulation. Moreover, silencing of Krt17 led to cell cycle
      arrest at G1/S stage by decreasing cyclin E1 and cyclin D expression. In
      conclusion, our findings revealed Krt17 can be used as a novel predictive
      biomarker, thus providing a novel therapeutic target for GC patients.

PMID- 29344282
TI  - Clinical Significance of Glycoprotein Non-metastatic B and Its Association with
      EGFR/HER2 in Gastrointestinal Cancer.
AB  - Glycoprotein non-metastatic B (GPNMB), a type I transmembrane glycoprotein, is
      overexpressed in melanoma and breast cancer and promotes cancer-cell invasion and
      motility. We previously reported cross-talk between GPNMB and human epidermal
      growth factor receptor 2 (HER2) in breast cancer, suggesting that GPNMB might
      play an important role in resistance to anti-HER2 therapy in breast cancer. Here,
      we clarified the association between GPNMB and HER-family proteins in
      gastrointestinal cancer by examining their relationships using gastric and
      colorectal cancer cell lines. We found that GPNMB depletion of by small
      interfering RNA increased epidermal growth factor receptor (EGFR) expression and
      phosphorylation through AKT8 virus oncogene cellular homolog (AKT) and mitogen
      activated protein kinase (MAPK) pathways. Additionally, treatment with cetuximab
      (CTX) also increased GPNMB expression, and combination therapy consisting of
      GPNMB depletion and CTX treatment significantly suppressed cell growth in
      colorectal cancer cell lines, but not in gastric cancer cell lines. Furthermore,
      we also evaluated changes in GPNMB expression in vivo, with immunohistochemistry
      detecting GPNMB overexpression in a colorectal cancer patient following anti-EGFR
      therapy. These results suggested possible cross-talk between GPNMB and EGFR, and
      that GPNMB might play an important role in resistance to anti-EGFR therapy in
      gastrointestinal cancer.

PMID- 29344283
TI  - Antigen presentation of the Oct4 and Sox2 peptides by CD154-activated B
      lymphocytes enhances the killing effect of cytotoxic T lymphocytes on tumor stem
      like cells derived from cisplatin-resistant lung cancer cells.
AB  - The present study investigated whether antigen presentation of the Oct4 and Sox2
      peptides by CD154-activated B lymphocytes can enhance the killing effect of CD8+
      cytotoxic T lymphocytes (CTLs) on lung stem-like cancer cells (SLCCs). The CTLs
      were generated using an accelerated co-cultured dendritic cells (DC) (acDC) assay
      by incubating human peripheral blood mononuclear cells (PBMCs) from non-small
      cell lung cancer patients with antigen peptides of Oct4 and Sox2 in the presence
      of several DC-activating agents. CD154+ NIH3T3 cells prepared by CD154 lentiviral
      transfection were used as feeder layer to activate primary B cells (CD19+)
      obtained from PBMCs. Activated B cells were co-cultured with CTLs to present
      antigen peptides of Oct4 and Sox2. CTLs co-cultured with activated B cells were
      evaluated for the levels of secreted inflammatory cytokines using ELISA. In
      addition, the killing effect of the CTLs on SLCCs derived from cisplatin
      resistant strain of human lung cancer cell line PC9 was evaluated by flow
      cytometry using CFSE labeling of the target cells. After the acDC assay, the
      PBMCs exhibited a significant (p<0.01) increase in the population of CD8+/CD3+
      cells, indicating successful preparation of CTLs. The primary B cells cultured on
      the CD154+ NIH3T3 feeder layer resulted in significant (p<0.01) increase in the
      proportions of population expressing CD80, CD86, or HLA-A, indicating successful
      activation of the B cells. The co-culture of CTLs with CD154-activated B cells
      presenting the Oct4 and Sox2 peptides caused significant increase in the levels
      of secretory inflammatory cytokines and exhibited enhanced killing of the SLCCs
      derived from cisplatin-resistant PC9 cells. Antigen presentation of the Oct4 and
      Sox2 peptides by CD154-activated B cells can enhance the killing effect of CTLs
      towards lung SLCCs.

PMID- 29344285
TI  - Long noncoding RNA H19 derived miR-675 regulates cell proliferation by down
      regulating E2F-1 in human pancreatic ductal adenocarcinoma.
AB  - The long noncoding RNA (lncRNA) H19 has been proven to be overexpressed in human
      pancreatic ductal adenocarcinoma (PDAC). H19-induced PDAC cell proliferation is
      cell cycle-dependent by modulating E2F-1. However, the mechanism of how H19
      regulates E2F-1 remains unclear. In this study, we investigated the expression of
      miR-675 in PDAC tumours and cells, the biological function of miR-675 in PDAC
      cell proliferation and the possible relationship among H19, miR-675 and E2F-1. As
      a transcript of the first exon of H19, the level of miR-675 was negatively
      correlated with H19 expression in microdissected PDAC tissues (r=-0.0646,
      P=0.001). The serum miR-675 expression was significantly down-regulated in
      patients with PDAC compared to those in healthy individuals. Moreover, an
      evaluation of five PDAC cases showed that there was a remarkable increase of
      serum miR-675 levels after resection of the primary tumours. Ectopic
      overexpression of miR-675 in AsPC-1 and PANC-1 cells decreased cell viability,
      the colony-forming ability and the percentage of cells in S phase; contrarily,
      miR-675 knockdown resulted in enhanced cell proliferation. Furthermore, the
      suppressed cell proliferation caused by H19 knockdown could be rescued by
      inhibiting miR-675 expression. Additionally, intratumoural injection of either
      miR-675 agomir or antagomir could significantly affect tumour growth in vivo.
      Both the bioinformatic prediction and luciferase activity assay confirmed that
      E2F-1 was a direct target of miR-675. And the decrease of E2F-1 protein
      expression caused by siH19 could be partially reversed by miR-675 knockdown. We
      concluded that there might be a H19/miR-675/E2F-1 regulatory loop in cell cycle
      modulation. Serum miR-675 might serve as a potential biomarker for not only early
      diagnosis but also outcome prediction in PDAC.

PMID- 29344284
TI  - miR-149 in Human Cancer: A Systemic Review.
AB  - MicroRNAs (miRNAs) are small noncoding RNAs that regulate post-transcriptional
      gene expression via binding to the 3'-untranslated region (3'-UTR) of targeted
      mRNAs. They are reported to play important roles in tumorigenesis and progression
      of various cancers. Among them, miR-149 was confirmed to be aberrantly regulated
      in various tumors. In this review, we provide a complex overview of miR-149,
      particularly summarize the critical roles of it in cancers and expect to lay the
      foundation for future works on this important microRNA.

PMID- 29344286
TI  - Identification of Biomarker for Cutaneous Squamous Cell Carcinoma Using
      Microarray Data Analysis.
AB  - Cutaneous squamous cell carcinoma (CSCC) is one of the most malignant tumors
      worldwide. We aimed to explore the molecular mechanism of this CSCC and screen
      feature genes that can function as the biomarker of CSCC and thus provide a
      theoretical basis for the pathogenesis research and development of medicine. The
      method of microarray data analysis was used in this study to explore the
      differentially expressed genes between tissues of normal specimens and tissues of
      patients with CSCC. Besides, functional enrichment analysis and signal pathway
      were performed on these genes to screen the feature genes that are closely
      associated with CSCC can function as the potential biomarkers of CSCC.A total of
      53 samples from two datasets, GSE45216 and GSE45164, were used in the
      differentially expressed analysis. And as a result, a total of 833 genes were
      screened out, including 465 up-regulated genes and 215 down-regulated genes.
      Candidate genes, including up-regulated genes like S100A12, MMP1, DEFB4B/DEFB4A,
      KRT16 and PI3, and down-regulated genes like EGR3, LRP4, C14orf132, PAMR1, CCL27,
      and KRT2 were screened out. All these genes were testified in the dataset of
      GSE66359. The result showed that only three genes, KRT16, PI3 and EGR3, were
      mostly differentially expressed and only EGR3 had the same expression pattern
      with both datasets, GSE45216 and GSE45164.Of note, EGR3 gene was found to be the
      most differentially expressed gene in cutaneous squamous cell carcinoma, which
      had the potential to function as the candidate genes and help in the diagnosis
      and prognostic treatments of CSCC.

PMID- 29344287
TI  - Role of miR-483 in digestive tract cancers: from basic research to clinical
      value.
AB  - Digestive tract cancers (DTCs) is the most common malignant tumors in the world.
      Despite surgery and medical technology have witnessed the increasing development
      and sharp advancement in the past decade, DTCs remain a critical concern with
      high morbidity and mortality. Since a class of small noncoding RNAs termed miRNAs
      were identified several years ago, increasing studies have attempted to
      illustrate the relationship between the specific miRNAs dysregulated expression
      levels and the diseases phenotypic changes. For example, microRNA-483 (miR-483)
      aberrant expression plays a pivotal part in tumor biology in a variety of human
      cancer, including DTCs. In this review, we focus on the present key findings from
      recent profiling studies, discuss the use of miR-483 as a novel biomarker for
      DTCs. At the same time, we emphasize the significant diversities and technical
      difficulties must be overcome before clinically relevant signatures arose. It is
      believed that this might provide researchers an insight into the molecular
      targeting cancer treatment.

PMID- 29344288
TI  - GP73 level determines chemotherapeutic resistance in human hepatocellular
      carcinoma cells.
AB  - Objective GP73 is a new hepatocellular carcinoma (HCC) marker, which is highly
      expressed in hepatocellular carcinoma and closely relates to prognosis. This
      study was to investigate the effects of GP73 on cellular proliferation,
      apoptosis, oxaliplatin (OXA) resistance and secretory clusterin (sCLU) of HCC
      cells. Materials and Methods Western blot and immunofluorescence was used to
      detect the expression of GP73 in 8 types of commonly used HCC cell lines. Drug
      resistance was induced by increasing concentration gradient method. The drug
      resistant human HCC cell lines underwent GP73 overexpression or inhibition. Flow
      cytometry were used to detect the proliferation and apoptosis of HCC cell lines.
      The changes of sCLU were detected by enzyme-linked immunosorbent assay (ELISA).
      Results The expression of GP73 in MHC-97H cells was the highest and in Hep3B
      cells the lowest. The expression of GP73 was found further elevated in OXA
      resistant MHC-97H cells. After the knockdown of GP73 in OXA-resistant 97H cells,
      the IC50 of OXA decreased and the ability of cell proliferation decreased
      significantly. After over-expression of GP73 in OXA-resistant Hep3B cells, the
      IC50 of OXA increased and the cell proliferation ability increased, showing that
      GP73 is critical for OXA resistant in HCC cell lines; No significant change of
      sCLU level in GP73 overexpressed Hep3B and GP73 blocked MHCC-97H were identified.
      Conclusion The expression level of GP73 is critical for the resistance of OXA in
      HCC cell lines.

PMID- 29344289
TI  - Limb-bud and Heart Overexpression Inhibits the Proliferation and Migration of
      PC3M Cells.
AB  - Background: The limb-bud and heart gene (LBH) was discovered in the early 21st
      century and is specifically expressed in the mouse embryonic limb and heart
      development. Increasing evidences have indicated that LBH not only plays an
      important role in embryo development, it is also closely correlated with the
      occurance and progression of many tumors. However, its function in prostate
      cancer (PCa) is still not well understood. Here, we explored the effects of LBH
      on the proliferation and migration of the PCa cell line PC3M. Methods: LBH
      expression in tissues and cell lines of PCa was detected by immunohistochemistry
      and Western blotting. Lentivirus was used to transduct the LBH gene into the PC3M
      cells. Stable LBH-overexpressing PC3M-LBH cells and PC3M-NC control cells were
      obtained via puromycin screening. Cell proliferation was examined using the 3
      (4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Cell
      cycle distribution and apoptosis rate were investigated using flow cytometry.
      Cell migration was studied using the Transwell assay. Results: LBH expression
      level was down-regulated in 3 different PCa cell lines, especially in PC3M cells,
      compared with the normal prostate epithelial cells(RWPE-1). Cell lines of LBH
      upregulated PC3M-LBH and PC3M-NC control were successfully constructed.
      Significantly increased LBH expression level and decreased cyclin D1 and cyclin
      E2 expression level was found in PC3M-LBH cells as compared to the PC3M-NC cells.
      The overexpression of LBH significantly inhibited PC3M cell proliferation in
      vitro and tumor growth in nude mice. LBH overexpression in PC3M cell, also
      induced cell cycle G0/G1 phase arrest and decreased the migration of PC3M cells.
      Conclusions: Our results reveal that LBH expression is down-regulated in the
      tissue and cell lines of PCa. LBH overexpression inhibits PC3M cell proliferation
      and tumor growth by inducing cell cycle arrest through down-regulating cyclin
      D1and cyclin E2 expression. LBH might be a therapeutic target and potential
      diagnostic marker in PCa.

PMID- 29344290
TI  - Prophylactic cranial irradiation in resected small cell lung cancer: A systematic
      review with meta-analysis.
AB  - Background: The use of PCI in early operable patients with small cell lung cancer
      (SCLC) is still controversial. Therefore, we conducted a systematic review with
      meta-analysis to investigate the effects of PCI in resected SCLC patients.
      Methods: Relevant studies were identified from PubMed and EMBASE databases, the
      pooled hazard risks were obtained by the random-effects model. We also analyzed
      the brain metastasis (BM) risk in p-stage I patients without PCI. Results: Five
      retrospective studies were identified and a total of 1691 patients were included
      in our analysis, 315 of them received PCI. For all the resected patients, PCI was
      associated with improved overall survival (HR: 0.52, 95% CI: 0.33-0.82), and
      reduced brain metastasis risk (RR: 0.50, 95%CI: 0.32-0.78). However, with regard
      to p-stage I patients, no survival benefit was brought by PCI (HR: 0.87, 95% CI:
      0.34-2.24). Moreover, the pooled analysis of 7 studies found that the 5-year
      brain metastasis risk was relatively low (12%, 95% CI: 8%-17%) for p-stage I
      patients without PCI. Conclusions: PCI might be associated with a favorable
      survival advantage and reduced BM risk in complete resected SCLC patients, except
      for p-stage I patients.

PMID- 29344291
TI  - In Vivo Double Targeting of C26 Colon Carcinoma Cells and Microenvironmental
      Protumor Processes Using Liposomal Simvastatin.
AB  - Purpose: Besides cholesterol lowering effects, simvastatin (SIM) at very high
      doses possesses antitumor actions. Moreover our previous studies demonstrated
      that tumor-targeted delivery of SIM by using long-circulating liposomes (LCL)
      improved the therapeutic index of this drug in murine melanoma-bearing mice. To
      evaluate whether this finding can be exploited for future therapy of colorectal
      cancer the antitumor activity and the underlying mechanisms of long-circulating
      liposomal simvastatin (LCL-SIM) efficacy for inhibition of C26 murine colon
      carcinoma growth in vivo were investigated. Materials and Methods: To find LCL
      SIM dose with the highest therapeutic index, dose-response relationship and side
      effects of different LCL-SIM doses were assessed in C26 colon carcinoma-bearing
      mice. The underlying mechanisms of LCL-SIM versus free SIM treatments were
      investigated with regard to their actions on C26 cell proliferation and apoptosis
      (via tumor tissues immunostaining for PCNA and Bax markers), tumor inflammation
      (via western blot analysis of NF-kappaBeta production), angiogenesis (using an
      angiogenic protein array), and oxidative stress (by HPLC assessment of
      malondialdehyde). Results: Our findings suggest that LCL-SIM antitumor activity
      on C26 colon carcinoma is a result of the tumor-targeting property of the
      liposome formulation, as free SIM treatment was ineffective. Moreover, LCL-SIM
      exerted significant antiproliferative and pro-apoptotic actions on C26 cells,
      notable suppressive effects on two main supportive processes for tumor
      development, inflammation and angiogenesis, and only slight anti-oxidant actions.
      Conclusion: Our data proved that LCL-SIM antitumor activity in C26 colon
      carcinoma was based on cytotoxic effects on these cancer cells and suppressive
      actions on tumor angiogenesis and inflammation.

PMID- 29344293
TI  - Ligand Activation of PPARgamma by Ligustrazine Suppresses Pericyte Functions of
      Hepatic Stellate Cells via SMRT-Mediated Transrepression of HIF-1alpha.
AB  - Rationale: Hepatic stellate cells (HSCs) are liver-specific pericytes regulating
      vascular remodeling during hepatic fibrosis. Here, we investigated how
      ligustrazine affects HSC pericyte functions. Methods: Rat HSC-T6 and human HSC
      LX2 cells were cultured, and multiple molecular experiments including real-time
      PCR, Western blot, flow cytometry, immunofluorescence, electrophoretic mobility
      shift assay and co-immunoprecipitation were used to elucidate the underlying
      mechanisms. Molecular simulation and site-directed mutagenesis were performed to
      uncover the target molecule of ligustrazine. Rats were intoxicated with CCl4 for
      evaluating ligustrazine's effects in vivo. Results: Ligustrazine inhibited
      angiogenic cytokine production, migration, adhesion and contraction in HSCs, and
      activated PPARgamma. Selective PPARgamma inhibitor GW9662 potently abrogated
      ligustrazine suppression of HSC pericyte functions. Additionally, HIF-1alpha
      inhibitor PX-478 repressed HSC pericyte functions, and ligustrazine inhibited the
      transcription of HIF-1alpha, which was diminished by GW9662. Moreover,
      ligustrazine downregulation of HIF-1alpha was rescued by knockdown of SMRT, and
      ligustrazine increased PPARgamma physical interaction with SMRT, which was
      abolished by GW9662. These findings collectively indicated that activation of
      PPARgamma by ligustrazine led to transrepression of HIF-1alpha via a SMRT
      dependent mechanism. Furthermore, molecular docking evidence revealed that
      ligustrazine bound to PPARgamma in a unique double-molecule manner via hydrogen
      bonding with the residues Ser289 and Ser342. Site-directed mutation of Ser289
      and/or Ser342 resulted in the loss of ligustrazine transrepression of HIF-1alpha
      in HSCs, indicating that interactions with both the residues were indispensable
      for ligustrazine effects. Finally, ligustrazine improved hepatic injury,
      angiogenesis and vascular remodeling in CCl4-induced liver fibrosis in rats.
      Conclusions: We discovered a novel ligand activation pattern for PPARgamma
      transrepression of the target gene with therapeutic implications in HSC pericyte
      biology and liver fibrosis.

PMID- 29344292
TI  - Galectin-3 Activation and Inhibition in Heart Failure and Cardiovascular Disease:
      An Update.
AB  - Galectin-3 is a versatile protein orchestrating several physiological and
      pathophysiological processes in the human body. In the last decade, considerable
      interest in galectin-3 has emerged because of its potential role as a biotarget.
      Galectin-3 is differentially expressed depending on the tissue type, however its
      expression can be induced under conditions of tissue injury or stress. Galectin-3
      overexpression and secretion is associated with several diseases and is
      extensively studied in the context of fibrosis, heart failure, atherosclerosis
      and diabetes mellitus. Monomeric (extracellular) galectin-3 usually undergoes
      further "activation" which significantly broadens the spectrum of biological
      activity mainly by modifying its carbohydrate-binding properties. Self
      interactions of this protein appear to play a crucial role in regulating the
      extracellular activities of this protein, however there is limited and
      controversial data on the mechanisms involved. We therefore summarize (recent)
      literature in this area and describe galectin-3 from a binding perspective
      providing novel insights into mechanisms by which galectin-3 is known to be
      "activated" and how such activation may be regulated in pathophysiological
      scenarios.

PMID- 29344295
TI  - Peptide receptor radionuclide therapy as a new tool in treatment-refractory
      sarcoidosis - initial experience in two patients.
AB  - Sarcoidosis is a multisystem granulomatous disorder of unknown etiology that can
      involve virtually all organ systems. Whereas most patients present without
      symptoms, progressive and disabling organ failure can occur in up to 10% of
      subjects. Somatostatin receptor (SSTR)-directed peptide receptor radionuclide
      therapy (PRRT) has recently received market authorization for treatment of SSTR
      positive neuroendocrine tumors. Methods: We describe the first case series
      comprising two patients with refractory multi-organ involvement of sarcoidosis
      who received 4 cycles of PRRT. Results: PRRT was well-tolerated without any acute
      adverse effects. No relevant toxicities could be recorded during follow-up.
      Therapy resulted in partial response accompanied by a pronounced reduction in
      pain (patient #1) and stable disease regarding morphology as well as disease
      activity (patient #2), respectively. Conclusion: Peptide receptor radionuclide
      therapy in sarcoidosis is feasible and might be a new valuable tool in patients
      with otherwise treatment-refractory disease. Given the long experience with and
      good tolerability of PRRT, further evaluation of this new treatment option for
      otherwise treatment-refractory sarcoidosis in larger patient cohorts is
      warranted.

PMID- 29344294
TI  - Cardiomyocyte-Restricted Low Density Lipoprotein Receptor-Related Protein 6
      (LRP6) Deletion Leads to Lethal Dilated Cardiomyopathy Partly Through Drp1
      Signaling.
AB  - Low density lipoprotein receptor-related protein 6 (LRP6), a wnt co-receptor,
      regulates multiple functions in various organs. However, the roles of LRP6 in the
      adult heart are not well understood. Methods: We observed LRP6 expression in
      heart with end-stage dilated cardiomyopathy (DCM) by western blot. Tamoxifen
      inducible cardiac-specific LRP6 knockout mouse was constructed. Hemodynamic and
      echocardiographic analyses were performed to these mice. Results: Cardiac LRP6
      expression was dramatically decreased in patients with end-stage dilated
      cardiomyopathy (DCM) compared to control group. Tamoxifen-inducible cardiac
      specific LRP6 knockout mice developed acute heart failure and mitochondrial
      dysfunction with reduced survival. Proteomic analysis suggests the fatty acid
      metabolism disorder involving peroxisome proliferator-activated receptors (PPARs)
      signaling in the LRP6 deficient heart. Accumulation of mitochondrial targeting to
      autophagosomes and lipid droplet were observed in LRP6 deletion hearts. Further
      analysis revealed cardiac LRP6 deletion suppressed autophagic degradation and
      fatty acid utilization, coinciding with activation of dynamin-related protein 1
      (Drp1) and downregulation of nuclear TFEB (Transcription factor EB). Injection of
      Mdivi-1, a Drp1 inhibitor, not only promoted nuclear translocation of TFEB, but
      also partially rescued autophagic degradation, improved PPARs signaling, and
      attenuated cardiac dysfunction induced by cardiac specific LRP6 deletion.
      Conclusions: Cardiac LRP6 deficiency greatly suppressed autophagic degradation
      and fatty acid utilization, and subsequently leads to lethal dilated
      cardiomyopathy and cardiac dysfunction through activation of Drp1 signaling. It
      suggests that heart failure progression may be attenuated by therapeutic
      modulation of LRP6 expression.

PMID- 29344296
TI  - CDK16 Phosphorylates and Degrades p53 to Promote Radioresistance and Predicts
      Prognosis in Lung Cancer.
AB  - Rationale: Radioresistance is considered the main cause of local relapse in lung
      cancer. However, the molecular mechanisms of radioresistance remain poorly
      understood. This study investigates the role of CDK16 in radioresistance of human
      lung cancer cells. Methods: The expression levels of CDK16 were determined by
      immunohistochemistry in lung cancer tissues and adjacent normal lung tissues.
      Immunoprecipitation assay and GST pulldown were utilized to detect the protein
      protein interaction. The phosphorylation of p53 was evaluated by in vitro kinase
      assay. Poly-ubiquitination of p53 was examined by in vivo ubiquitination assay.
      Cell growth and apoptosis, ROS levels and DNA damage response were measured for
      functional analyses. Results: We showed that CDK16 is frequently overexpressed in
      lung cancer cells and tissues, and high levels of CDK16 are correlated with lymph
      node stage and poor prognosis in lung cancer patients. Furthermore, we provided
      evidence that CDK16 binds to and phosphorylates p53 at Ser315 site to inhibit
      transcriptional activity of p53. Moreover, we uncovered that this phosphorylation
      modification accelerates p53 degradation via the ubiquitin/proteasome pathway.
      Importantly, we demonstrated that CDK16 promotes radioresistance by suppressing
      apoptosis and ROS production as well as inhibiting DNA damage response in lung
      cancer cells in a p53-dependent manner. Conclusion: Our findings suggest that
      CDK16 negatively modulates p53 signaling pathway to promote radioresistance, and
      therefore represents a promising therapeutic target for lung cancer radiotherapy.

PMID- 29344297
TI  - Mesoporous Carbon Nanospheres as a Multifunctional Carrier for Cancer
      Theranostics.
AB  - Optical nanomaterials with intense absorption in near-infrared (NIR) region hold
      great promise for biomedical applications such as photothermal therapy (PTT) and
      photoacoustic imaging (PAI). In this work, we report mesoporous carbon
      nanospheres (Meso-CNs) with broadband and intense absorption in the UV-Vis-NIR
      region (300-1400 nm) and explore their potential as a multifunctional platform
      for photoacoustic imaging and chemo-photothermal therapy. Methods: Meso-CNs were
      prepared by a "silica-assisted" synthesis strategy and characterized by
      transmission electron microscope and optical spectroscopy. We investigated the
      photothermal conversion and photoacoustic imaging of Meso-CNs in comparison with
      single-walled carbon nanotubes (SWCNTs), graphene and gold nanorods (GNRs). In
      vitro cellular assays and in vivo chemo-photothermal combination therapy were
      performed. Results: The absorption coefficients of Meso-CNs are 1.5-2 times
      higher than those of SWCNTs and graphene and are comparable to those of GNRs in
      both the first and the second near-infrared optical windows (NIR-I and NIR-II) of
      tissues. When exposed to an NIR laser, the photothermal and photoacoustic signal
      generation of Meso-CNs are also stronger than those of SWCNTs, graphene, and
      GNRs. DOX was loaded into Meso-CNs with a high efficiency (35 wt%) owing to the
      unique mesoporous structure. Particularly, the drug release from Meso-CNs is
      sensitive to both pH and NIR light stimulation. In vivo chemo-photothermal
      combination therapy demonstrates a remarkable inhibition effect on tumor growth
      under NIR laser treatment. Conclusions: We have developed Meso-CNs for
      photothermal conversion and photoacoustic imaging. The porous structure also
      serves as a drug carrier and the drug release can be controlled by pH and
      external light. The high drug loading capacity, superior photothermal and
      photoacoustic generation, together with the apparent chemo-photothermal
      therapeutic effect, make Meso-CNs a promising platform for cancer theranostics.

PMID- 29344298
TI  - AKR1C1 Activates STAT3 to Promote the Metastasis of Non-Small Cell Lung Cancer.
AB  - Metastasis is the leading cause of mortality for human non-small cell lung cancer
      (NSCLC). However, it is difficult to target tumor metastasis because the
      molecular mechanisms underlying NSCLC invasion and migration remain unclear.
      Methods: GEO data analyses and IHC analyses were performed to identify that the
      expression level of AKR1C1, a member of human aldo-keto reductase family, was
      highly elevated in patients with metastasis or metastatic foci of NSCLC patients.
      Functional analyses (in vitro and in vivo) and quantitative genomic analyses were
      preformed to confirm the pro-metastatic effects of AKR1C1 and the underlying
      mechanisms. The correlation of AKR1C1 with the prognosis of NSCLC patients was
      evaluated using Kaplan-Meier analyses. Results: in NSCLC patients, AKR1C1
      expression was closely correlated with the metastatic potential of tumors. AKR1C1
      overexpression in nonmetastatic cancer cells significantly promoted metastasis
      both in vitro and in vivo, whereas depletion of AKR1C1 in highly metastatic
      tumors potently alleviated these effects. Quantitative genomic and functional
      analyses revealed that AKR1C1 directly interacted with STAT3 and facilitated its
      phosphorylation-thus reinforcing the binding of STAT3 to the promoter regions of
      target genes-and then transactivated these genes, which ultimately promoted tumor
      metastasis. Further studies showed that AKR1C1 might facilitate the interaction
      of STAT3 with its upstream kinase JAK2. Intriguingly, AKR1C1 exerted these pro
      metastatic effects in a catalytic-independent manner. In addition, a significant
      correlation between AKR1C1 and STAT3 pathway was observed in the metastatic foci
      of NSCLC patients, and the AKR1C1-STAT3 levels were highly correlated with a poor
      prognosis in NSCLC patients. Conclusions: taken together, we show that AKR1C1 is
      a potent inducer of NSCLC metastasis. Our study uncovers the active function of
      AKR1C1 as a key component of the STAT3 pathway, which promotes lung cancer
      metastasis, and highlights a candidate therapeutic target to potentially improve
      the survival of NSCLC patients with metastatic disease.

PMID- 29344299
TI  - Enhanced Synergism of Thermo-chemotherapy For Liver Cancer with Magnetothermally
      Responsive Nanocarriers.
AB  - A combination of magnetic hyperthermia and magnetothermally-facilitated drug
      release system was developed as a promising strategy for liver cancer therapy.
      The thermosensitive copolymer, 6sPCL-b-P(MEO2MA-co-OEGMA) shows a good
      temperature-controlled drug release response. Mn-Zn ferrite magnetic
      nanoparticles (MZF-MNPs) exhibit a strong magnetic thermal effect with an
      alternating magnetic field (AMF). Owing to its high magnetic sensitivity, the
      magnetothermally-responsive nanocarrier/doxorubicin (MTRN/DOX) can be
      concentrated in the tumor site efficiently through magnetic targeting. Given this
      information, we synthesized MTRN/DOX which was composed of MZF-MNPs,
      thermosensitive copolymer drug carriers, and the chemotherapeutic drug---DOX, to
      study its anticancer effects both in vitro and in vivo.METHODS: MTRN/DOX was
      designed and prepared. Firstly, we investigated the accumulation effects of
      MTRN/DOX by Prussian blue staining, transmission electron microscopy (TEM), laser
      scanning confocal microscopy (LSCM) and conducted 7.0 T MRI. Following this, the
      magnetothermal effects of MTRN/DOX were studied using an infrared thermal camera.
      DOX uptake, distribution, and retention in tumor cells and the distribution of
      MTRN/DOX in vivo were then analyzed via LSCM, flow cytometry and live
      fluorescence imaging. Lastly, its anticancer effects were evaluated by MTT, AM/PI
      staining, Annexin-VFITC/PI staining and comparison of relative tumor volume.
      RESULTS: We found that MTRN/DOX can be efficiently concentrated in the tumor site
      through magnetic targeting, increasing the uptake of DOX by tumor cells, and
      prolonging the retention time of the drug within the tumors. MTRN/DOX showed good
      magnetothermal effects both in vitro and in vivo. Based on the above results,
      MTRN/DOX had significant anticancer effects. CONCLUSIONS: MTRN/DOX causes
      temporal-spatial synchronism of thermo-chemotherapy and together with
      chemotherapeutic drugs, produces a synergistic effect, which enhances the
      sensitivity of tumor cells to DOX and reduces their side effects.

PMID- 29344300
TI  - General Anesthesia Inhibits the Activity of the "Glymphatic System".
AB  - INTRODUCTION: According to the "glymphatic system" hypothesis, brain waste
      clearance is mediated by a continuous replacement of the interstitial milieu by a
      bulk flow of cerebrospinal fluid (CSF). Previous reports suggested that this
      cerebral CSF circulation is only active during general anesthesia or sleep, an
      effect mediated by the dilatation of the extracellular space. Given the
      controversies regarding the plausibility of this phenomenon and the limitations
      of currently available methods to image the glymphatic system, we developed
      original whole-brain in vivo imaging methods to investigate the effects of
      general anesthesia on the brain CSF circulation. METHODS: We used magnetic
      resonance imaging (MRI) and near-infrared fluorescence imaging (NIRF) after
      injection of a paramagnetic contrast agent or a fluorescent dye in the cisterna
      magna, in order to investigate the impact of general anesthesia (isoflurane,
      ketamine or ketamine/xylazine) on the intracranial CSF circulation in mice.
      RESULTS:In vivo imaging allowed us to image CSF flow in awake and anesthetized
      mice and confirmed the existence of a brain-wide CSF circulation. Contrary to
      what was initially thought, we demonstrated that the parenchymal CSF circulation
      is mainly active during wakefulness and significantly impaired during general
      anesthesia. This effect was especially significant when high doses of anesthetic
      agent were used (3% isoflurane). These results were consistent across the
      different anesthesia regimens and imaging modalities. Moreover, we failed to
      detect a significant change in the brain extracellular water volume using
      diffusion weighted imaging in awake and anesthetized mice. CONCLUSION: The
      parenchymal diffusion of small molecular weight compounds from the CSF is active
      during wakefulness. General anesthesia has a negative impact on the intracranial
      CSF circulation, especially when using a high dose of anesthetic agent.

PMID- 29344301
TI  - WST11 Vascular Targeted Photodynamic Therapy Effect Monitoring by Multispectral
      Optoacoustic Tomography (MSOT) in Mice.
AB  - Objective: Monitoring emerging vascular-targeted photodynamic therapy (VTP) and
      understanding the time-dynamics of treatment effects remains challenging. We
      interrogated whether handheld multispectral optoacoustic tomography (MSOT) could
      noninvasively monitor the effect of VTP using WST11, a vascular-acting
      photosensitizer, on tumor tissues over time using a renal cell cancer mouse
      model. We also investigated whether MSOT illumination can induce VTP, to
      implement a single-modality theranostic approach. Materials and Methods: Eight
      BalB/c mice were subcutaneously implanted with murine renal adenocarcinoma cells
      (RENCA) on the flank. Three weeks later VTP was performed (10 min continuous
      illumination at 753 nm following intravenous infusion using WST11 or saline as
      control. Handheld MSOT images were collected prior to VTP administration and
      subsequently thereafter over the course of the first hour, at 24 and 48 h. Data
      collected were unmixed for blood oxygen saturation in tissue (SO2) based on the
      spectral signatures of deoxy- and oxygenated hemoglobin. Changes in oxygen
      saturation over time, relative to baseline, were examined by paired t-test for
      statistical significance (p < 0.05). In-vivo findings were corroborated by
      histological analyses of the tumor tissue. Results: MSOT is shown to prominently
      resolve changes in oxygen saturation in tumors within the first 20 min post WST11
      VTP treatment. Within the first hour post-treatment, SO2 decreased by more than
      60% over baseline (p < 0.05), whereas it remained unchanged (p > 0.1) in the sham
      treated group. Moreover, unlike in the control group, SO2 in treated tumors
      further decreased over the course of 24 to 48 h post-treatment, concomitant with
      the propagation of profound central tumor necrosis present in histological
      analysis. We further show that pulsed MSOT illumination can activate WST11 as
      efficiently as the continuous wave irradiation employed for treatment.
      Conclusion: Handheld MSOT non-invasively monitored WST11-VTP effects based on the
      SO2 signal and detected blood saturation changes within the first 20 min post
      treatment. MSOT may potentially serve as a means for both VTP induction and real
      time VTP monitoring in a theranostic approach.

PMID- 29344302
TI  - Evans Blue Attachment Enhances Somatostatin Receptor Subtype-2 Imaging and
      Radiotherapy.
AB  - Purpose: Radionuclide therapy directed against tumors that express somatostatin
      receptors (SSTRs) has proven effective for the treatment of advanced, low- to
      intermediate-grade neuroendocrine tumors in the clinic. In clinical usage,
      somatostatin peptide-based analogs, labeled with therapeutic radionuclides,
      provide an overall response rate of about 30%, despite the high cumulative
      activity injected per patient. We set out to improve the effectiveness of
      somatostatin radiotherapy by preparing a chemical analog that would clear more
      slowly through the urinary tract and, concomitantly, have increased blood
      circulation half-life and higher targeted accumulation in the tumors.
      Experimental Design: We conjugated a common, clinically-used SST peptide
      derivative, DOTA-octreotate, to an Evans blue analog (EB), which reversibly binds
      to circulating serum albumin. The resulting molecule was used to chelate 86Y and
      90Y, a diagnostic and a therapeutic radionuclide, respectively. The imaging
      capabilities and the radiotherapeutic efficacy of the resulting radioligand was
      evaluated in HCT116/SSTR2, HCT116, and AR42J cell lines that express differing
      levels of SST2 receptors. Results: The synthesized radiopharmaceutical retained
      affinity and specificity to SSTR2. The new molecule also retained the high
      internalization rate of DOTA-octreotate, and therefore, showed significantly
      higher accumulation in SSTR2-positive tumors. Labeling of our novel EB-octreotate
      derivative with the therapeutic, pure beta emitter, 90Y, resulted in improved
      tumor response and survival rates of mice bearing SSTR2 xenografts and had long
      term efficacy when compared to DOTA-octreotate itself. Conclusions: The coupling
      of a targeted peptide, a therapeutic radionuclide, and the EB-based albumin
      binding provides for effective treatment of SSTR2-containing tumors.

PMID- 29344303
TI  - Erratum: Improvement of Prostate Cancer Diagnosis by Detecting PSA Glycosylation
      Specific Changes: Erratum.
AB  - [This corrects the article DOI: 10.7150/thno.15226.].

PMID- 29344304
TI  - Atherosclerosis is exacerbated by chitinase-3-like-1 in amyloid precursor protein
      transgenic mice.
AB  - Although the important role of amyloid precursor protein (APP) in vascular
      diseases associated with Alzheimer's disease (AD) has been demonstrated, the
      underlying molecular mechanisms and physiological consequences are unclear. We
      aimed to evaluate vascular inflammation and atherosclerosis in Swedish mutant of
      human APP transgenic (APPsw-Tg) and ApoE-/-/APPsw-Tg mice. We also aimed to
      explore the mechanisms underlying any changes observed in these mice compared
      with non-Tg controls. Methods: The transgenic and non-Tg mouse strains were
      subjected to partial ligation of the left carotid artery to induce
      atherosclerotic changes, which were measured using histological approaches,
      immunohistochemistry, quantitative polymerase chain reaction, and gene expression
      microarrays. Results: Our results showed increased vascular inflammation,
      arterial wall thickness, and atherosclerosis in APPsw-Tg and ApoE-/-/APPsw-Tg
      mice. We further found that the expression of chitinase-3-like-1 (Chi3l1) is
      increased in the APPsw-Tg mouse artery and Chi3l1 mediates endothelial cell (EC)
      inflammation and vascular smooth muscle cell (VSMC) activation, which in turn
      exacerbates atherosclerosis. In addition, using two publicly available microarray
      datasets from the dorsolateral prefrontal cortex of people with AD and unaffected
      controls as well as inflamed human umbilical vein endothelial cells, we found
      that Chi3l1 and associated inflammatory gene were significantly associated with
      AD, evaluated by co-expression network analysis and functional annotation.
      Knockdown of Chi3l1 in the arterial endothelium in vivo suppressed the
      development of atherosclerosis. We also show that microRNA 342-3p (miR-342-3p)
      inhibits EC inflammation and VSMC activation through directly targeting Chi3l1,
      and that APPsw increased Chi3l1 expression by reducing miR-342-3p expression in
      the arterial endothelium, promoting atherosclerosis. Conclusion: Our findings
      suggest that targeting Chi3l1 might provide new diagnostic and therapeutic
      strategies for vascular diseases in patients with AD.

PMID- 29344305
TI  - A Tumor-Activatable Theranostic Nanomedicine Platform for NIR Fluorescence-Guided
      Surgery and Combinatorial Phototherapy.
AB  - Fluorescence image-guided surgery combined with intraoperative therapeutic
      modalities has great potential for intraoperative detection of oncologic targets
      and eradication of unresectable cancer residues. Therefore, we have developed an
      activatable theranostic nanoplatform that can be used concurrently for two
      purposes: (1) tumor delineation with real-time near infrared (NIR) fluorescence
      signal during surgery, and (2) intraoperative targeted treatment to further
      eliminate unresected disease sites by non-toxic phototherapy. Methods: The
      developed nanoplatform is based on a single agent, silicon naphthalocyanine
      (SiNc), encapsulated in biodegradable PEG-PCL (poly (ethylene glycol)-b-poly(E
      caprolactone)) nanoparticles. It is engineered to be non-fluorescent initially
      via dense SiNc packing within the nanoparticle's hydrophobic core, with NIR
      fluorescence activation after accumulation at the tumor site. The activatable
      nanoplatform was evaluated in vitro and in two different murine cancer models,
      including an ovarian intraperitoneal metastasis-mimicking model. Furthermore,
      fluorescence image-guided surgery mediated by this nanoplatform was performed on
      the employed animal models using a Fluobeam(r) 800 imaging system. Finally, the
      phototherapeutic efficacy of the developed nanoplatform was demonstrated in vivo.
      Results: Our in vitro data suggest that the intracellular environment of cancer
      cells is capable of compromising the integrity of self-assembled nanoparticles
      and thus causes disruption of the tight dye packing inside the hydrophobic cores
      and activation of the NIR fluorescence. Animal studies demonstrated accumulation
      of activatable nanoparticles at the tumor site following systemic administration,
      as well as release and fluorescence recovery of SiNc from the polymeric carrier.
      It was also validated that the developed nanoparticles are compatible with the
      intraoperative imaging system Fluobeam(r) 800, and nanoparticle-mediated image
      guided surgery provides successful resection of cancer tumors. Finally, in vivo
      studies revealed that combinatorial phototherapy mediated by the nanoparticles
      could efficiently eradicate chemoresistant ovarian cancer tumors. Conclusion: The
      revealed properties of the activatable nanoplatform make it highly promising for
      further application in clinical image-guided surgery and combined phototherapy,
      facilitating a potential translation to clinical studies.

PMID- 29344306
TI  - 131I-Labeled Copper Sulfide-Loaded Microspheres to Treat Hepatic Tumors via
      Hepatic Artery Embolization.
AB  - Purpose: Transcatheter hepatic artery embolization therapy is a minimally
      invasive alternative for treating inoperable liver cancer but recurrence is
      frequent. Multifunctional agents, however, offer an opportunity for tumor
      eradication. In this study, we were aim to synthesized poly (lactic-co-glycolic
      acid) (PLGA) microspheres encapsulating hollow CuS nanoparticles (HCuSNPs) and
      paclitaxel (PTX) that were then labeled with radioiodine-131 (131I) to produce
      131I-HCuSNPs-MS-PTX. This compound combines the multi-theranostic properties of
      chemotherapy, radiotherapy and photothermal therapy. In addition, it can also be
      imaged with single photon emission computed tomography (SPECT) imaging and
      photoacoustic imaging. Methods: We investigated the value of therapeutic and
      imaging of 131I-HCuSNPs-MS-PTX in rats bearing Walker-256 tumor transplanted in
      the liver. After the intra-arterial (IA) injection of 131I-HCuSNPs-MS-PTX, 18F
      Fluorodeoxyglucose (18F-FDG) micro-positron emission tomography/computed
      tomography (micro-PET/CT) imaging was used to monitor the therapeutic effect.
      PET/CT findings were verified by immunohistochemical analysis. SPECT/CT and
      photoacoustic imaging were performed to demonstrate the distribution of 131I
      HCuSNPs-MS-PTX in vivo. Results: We found that embolization therapy in
      combination with chemotherapy, radiotherapy and photothermal therapy offered by
      131I-HCuSNPs-MS-PTX completely ablated the transplanted hepatic tumors at a
      relatively low dose. In comparison, embolization monotherapy or combination with
      one or two other therapies had less effective anti-tumor efficacy. The
      combination of SPECT/CT and photoacoustic imaging effectively confirmed
      microsphere delivery to the targeted tumors in vivo and guided the near-infrared
      laser irradiation. Conclusion: Our study suggests that there is a clinical
      theranostic potential for imaging-guided arterial embolization with 131I-HCuSNPs
      MS-PTX for the treatment of liver tumors.

PMID- 29344307
TI  - Dual turn-on fluorescence signal-based controlled release system for real-time
      monitoring of drug release dynamics in living cells and tumor tissues.
AB  - Controlled release systems with capabilities for direct and real-time monitoring
      of the release and dynamics of drugs in living systems are of great value for
      cancer chemotherapy. Herein, we describe a novel dual turn-on fluorescence signal
      based controlled release system (CDox), in which the chemotherapy drug
      doxorubicin (Dox) and the fluorescent dye (CH) are conjugated by a hydrazone
      moiety, a pH-responsive cleavable linker. CDox itself shows nearly no
      fluorescence as the fluorescence of CH and Dox is essentially quenched by the C=N
      isomerization and N-N free rotation. However, when activated under acidic
      conditions, CDox could be hydrolyzed to afford Dox and CH, resulting in dual turn
      on signals with emission peaks at 595 nm and 488 nm, respectively. Notably, CDox
      exhibits a desirable controlled release feature as the hydrolysis rate is limited
      by the steric hindrance effect from both the Dox and CH moieties. Cytotoxicity
      assays indicate that CDox shows much lower cytotoxicity relative to Dox, and
      displays higher cell inhibition rate to cancer than normal cells. With the aid of
      the dual turn-on fluorescence at different wavelengths, the drug release dynamics
      of CDox in living HepG2 and 4T-1 cells was monitored in double channels in a real
      time fashion. Importantly, two-photon fluorescence imaging of CDox in living
      tumor tissues was also successfully performed by high-definition 3D imaging. We
      expect that the unique controlled release system illustrated herein could provide
      a powerful means to investigate modes of action of drugs, which is critical for
      development of much more robust and effective chemotherapy drugs.

PMID- 29344308
TI  - "Albumin Hitchhiking" with an Evans Blue Analog for Cancer Theranostics.
AB  - Although 177Lu-DOTA-TATE was recently approved in Europe for the treatment of
      certain neuroendocrine tumors, continued development and optimization has been
      ongoing to further improve the therapeutic efficacy of somatostatin receptor 2
      targeted peptide receptor radionuclide therapy, as well as reducing the renal
      toxicity. In this work, the use of an Evans blue analog for "albumin hitchhiking"
      resulted in significant improvement in both the imaging performance and
      therapeutic efficacy of radiolabeled octreotate, as well as reducing the toxicity
      since much less radioactivity was used for therapy. Upon clinical translation,
      such "albumin hitchhiking" could make significant impact in the near future for
      cancer patient management.

PMID- 29344310
TI  - Drug Repurposing Screening Identifies Tioconazole as an ATG4 Inhibitor that
      Suppresses Autophagy and Sensitizes Cancer Cells to Chemotherapy.
AB  - Background: Tumor cells require proficient autophagy to meet high metabolic
      demands and resist chemotherapy, which suggests that reducing autophagic flux
      might be an attractive route for cancer therapy. However, this theory in clinical
      cancer research remains controversial due to the limited number of drugs that
      specifically inhibit autophagy-related (ATG) proteins. Methods: We screened FDA
      approved drugs using a novel platform that integrates computational docking and
      simulations as well as biochemical and cellular reporter assays to identify
      potential drugs that inhibit autophagy-required cysteine proteases of the ATG4
      family. The effects of ATG4 inhibitors on autophagy and tumor suppression were
      examined using cell culture and a tumor xenograft mouse model. Results:
      Tioconazole was found to inhibit activities of ATG4A and ATG4B with an IC50 of
      1.3 uM and 1.8 uM, respectively. Further studies based on docking and molecular
      dynamics (MD) simulations supported that tioconazole can stably occupy the active
      site of ATG4 in its open form and transiently interact with the allosteric
      regulation site in LC3, which explained the experimentally observed obstruction
      of substrate binding and reduced autophagic flux in cells in the presence of
      tioconazole. Moreover, tioconazole diminished tumor cell viability and sensitized
      cancer cells to autophagy-inducing conditions, including starvation and treatment
      with chemotherapeutic agents. Conclusion: Tioconazole inhibited ATG4 and
      autophagy to enhance chemotherapeutic drug-induced cytotoxicity in cancer cell
      culture and tumor xenografts. These results suggest that the antifungal drug
      tioconazole might be repositioned as an anticancer drug or chemosensitizer.

PMID- 29344311
TI  - Gilz-Activin A as a Novel Signaling Axis Orchestrating Mesenchymal Stem Cell and
      Th17 Cell Interplay.
AB  - Mesenchymal stem cells (MSC) are highly immunosuppressive cells able to reduce
      chronic inflammation through the active release of mediators. Recently, we showed
      that glucocorticoid-induced leucine zipper (Gilz) expression by MSC is involved
      in their therapeutic effect by promoting the generation of regulatory T cells.
      However, the mechanisms underlying this pivotal role of Gilz remain elusive.
      Methods and Results In this study, we have uncovered evidence that Gilz modulates
      the phenotype and function of Th1 and Th17 cells likely by upregulating the level
      of Activin A and NO2 secreted by MSC. Adoptive transfer experiments sustained
      this Gilz-dependent suppressive effect of MSC on Th1 and Th17 cell functions. In
      immunoregulatory MSC, obtained by priming with IFN-gamma and TNF-alpha, Gilz was
      translocated to the nucleus and bound to the promoters of inos and Activin betaA
      to induce their expression. The increased expression of Activin A directly
      impacted on Th17 cells fate by repressing their differentiation program through
      the activation of Smad3/2 and enhancing IL-10 production. Conclusion Our results
      reveal how Gilz controls inos and Activin betaA gene expression to ultimately
      assign immunoregulatory status to MSC able to repress the pathogenic Th17 cell
      differentiation program and uncover Activin A as a novel mediator of MSC in this
      process.

PMID- 29344309
TI  - Adult Stem Cells in Vascular Remodeling.
AB  - Understanding the contribution of vascular cells to blood vessel remodeling is
      critical for the development of new therapeutic approaches to cure cardiovascular
      diseases (CVDs) and regenerate blood vessels. Recent findings suggest that
      neointimal formation and atherosclerotic lesions involve not only inflammatory
      cells, endothelial cells, and smooth muscle cells, but also several types of stem
      cells or progenitors in arterial walls and the circulation. Some of these stem
      cells also participate in the remodeling of vascular grafts, microvessel
      regeneration, and formation of fibrotic tissue around biomaterial implants. Here
      we review the recent findings on how adult stem cells participate in CVD
      development and regeneration as well as the current state of clinical trials in
      the field, which may lead to new approaches for cardiovascular therapies and
      tissue engineering.

PMID- 29344312
TI  - An Endogenous Vaccine Based on Fluorophores and Multivalent Immunoadjuvants
      Regulates Tumor Micro-Environment for Synergistic Photothermal and Immunotherapy.
AB  - Recently, near-infrared (NIR) light-based photothermal therapy (PTT) has been
      widely applied in cancer treatment. However, in most cases, the tissue
      penetration depth of NIR light is not sufficient and thus photothermal therapy is
      unable to completely eradicate deep, seated tumors inevitably leading to
      recurrence of the tumor. Due to this significant limitation of NIR, improved
      therapeutic strategies are urgently needed. Methods: We developed an endogenous
      vaccine based on a novel nanoparticle platform for combinatorial photothermal
      ablation and immunotherapy. The design was based on fluorophore-loaded liposomes
      (IR-7-lipo) coated with a multivalent immunoadjuvant (HA-CpG). In vitro PTT
      potency was assessed in cells by LIVE/DEAD and Annexin V-FITC/PI assays. The
      effect on bone marrow-derived dendritic cells (BMDC) maturation and antigen
      presentation was evaluated by flow cytometry (FCM) with specific antibodies.
      After treatment, the immune cell populations in tumor micro-environment and the
      cytokines in the serum were detected by FCM and Elisa assay, respectively.
      Finally, the therapeutic outcome was investigated in an animal model. Results:
      Upon irradiation with 808 nm laser, IR-7-lipo induced tumor cell necrosis and
      released tumor-associated antigens, while the multivalent immunoadjuvant improved
      the expression of co-stimulatory molecules on BMDC and promoted antigen
      presentation. The combination therapy of PTT and immunotherapy regulated the
      tumor micro-environment, decreased immunosuppression, and potentiated host
      antitumor immunity. Most significantly, due to an enhanced antitumor immune
      response, combined photothermal immunotherapy was effective in eradicating tumors
      in mice and inhibiting tumor metastasis. Conclusion: This endogenous vaccination
      strategy based on synergistic photothermal and immunotherapy may provide a
      potentially effective approach for treatment of cancers, especially those
      difficult to be surgically removed.

PMID- 29344313
TI  - DNA methylation as a predictor of fetal alcohol spectrum disorder.
AB  - Background: Fetal alcohol spectrum disorder (FASD) is a developmental disorder
      that manifests through a range of cognitive, adaptive, physiological, and
      neurobiological deficits resulting from prenatal alcohol exposure. Although the
      North American prevalence is currently estimated at 2-5%, FASD has proven
      difficult to identify in the absence of the overt physical features
      characteristic of fetal alcohol syndrome. As interventions may have the greatest
      impact at an early age, accurate biomarkers are needed to identify children at
      risk for FASD. Building on our previous work identifying distinct DNA methylation
      patterns in children and adolescents with FASD, we have attempted to validate
      these associations in a different clinical cohort and to use our DNA methylation
      signature to develop a possible epigenetic predictor of FASD. Methods: Genome
      wide DNA methylation patterns were analyzed using the Illumina
      HumanMethylation450 array in the buccal epithelial cells of a cohort of 48
      individuals aged 3.5-18 (24 FASD cases, 24 controls). The DNA methylation
      predictor of FASD was built using a stochastic gradient boosting model on our
      previously published dataset FASD cases and controls (GSE80261). The predictor
      was tested on the current dataset and an independent dataset of 48 autism
      spectrum disorder cases and 48 controls (GSE50759). Results: We validated
      findings from our previous study that identified a DNA methylation signature of
      FASD, replicating the altered DNA methylation levels of 161/648 CpGs in this
      independent cohort, which may represent a robust signature of FASD in the
      epigenome. We also generated a predictive model of FASD using machine learning in
      a subset of our previously published cohort of 179 samples (83 FASD cases, 96
      controls), which was tested in this novel cohort of 48 samples and resulted in a
      moderately accurate predictor of FASD status. Upon testing the algorithm in an
      independent cohort of individuals with autism spectrum disorder, we did not
      detect any bias towards autism, sex, age, or ethnicity. Conclusion: These
      findings further support the association of FASD with distinct DNA methylation
      patterns, while providing a possible entry point towards the development of
      epigenetic biomarkers of FASD.

PMID- 29344315
TI  - A Topical Anti-inflammatory Healing Regimen Utilizing Conjugated Linolenic Acid
      for Use Post-ablative Laser Resurfacing of the Face: A Randomized, Controlled
      Trial.
AB  - Background: Fractionated, ablative lasers are usually associated with post
      treatment erythema, edema, and crusting, which can last from 5 to 14 days.
      Conjugated linolenic acid, an omega-5 fatty acid, has significant antioxidant and
      anti-inflammatory properties, and has been shown to stimulate keratinocyte
      proliferation and epidermal regeneration. By modulating the early inflammatory
      milieu and directly affecting skin structure and function, conjugated linolenic
      acid might therefore shorten downtime following fractionated ablative laser
      resurfacing of the face. Objective: To evaluate the efficacy and subject
      satisfaction of a topical regimen containing conjugated linolenic acid derived
      from pomegranate seed extract in accelerating wound healing and improving skin
      quality following fractionated ablative laser resurfacing of the face. Materials
      and Methods: Thirty-four subjects were enrolled and received fractionated CO2
      laser resurfacing. Subjects were randomized to use the test healing regimen
      (n=24) or 1% dimethicone ointment (n=10) post-procedure. The primary endpoint was
      the degree of erythema, edema, crusting, and exudation evaluated by a blinded
      clinician at post-treatment Days 1,3,7,10, 14, and 30. Secondary endpoints
      included a blinded evaluator assessment of the degree of wrinkling and elastosis
      using the Fitzpatrick-Goldman Wrinkle and Elastosis Scale; subject-assessed
      degree of pain, itching, tightness, oozing, and crusting; and subject overall
      satisfaction. Results: Subjects who applied the topical conjugated linolenic acid
      healing regimen experienced significantly reduced edema on post-procedure Day 3
      (p=0.04), and itching on Days 1 and 3 (p=0.03 and p=0.04). Both regimens produced
      significant improvements in wrinkling and elastosis at Days 14 and 30 post
      treatment, with conjugated linolenic acid outperforming placebo in improvements
      in wrinkling at Day 14. Both regimens were well tolerated with no statistical
      differences in adverse events or subject satisfaction. Conclusion: The topical
      conjugated linolenic acid formulation outperformed placebo by decreasing acute
      pruritus and edema, and enabling a faster positive outcome in wrinkle
      improvement. Additionally, topical conjugated linolenic acid does not raise any
      safety or tolerability issues as compared to current standard of care.

PMID- 29344314
TI  - Aberrant expression and DNA methylation of lipid metabolism genes in PCOS: a new
      insight into its pathogenesis.
AB  - Background: Polycystic ovary syndrome (PCOS), whose etiology remains uncertain,
      is a highly heterogenous and genetically complex endocrine disorder. The aim of
      this study was to identify differentially expressed genes (DEGs) in granulosa
      cells (GCs) from PCOS patients and make epigenetic insights into the pathogenesis
      of PCOS. Results: Included in this study were 110 women with PCOS and 119 women
      with normal ovulatory cycles undergoing in vitro fertilization acting as the
      control group. RNA-seq identified 92 DEGs unique to PCOS GCs in comparison with
      the control group. Bioinformatic analysis indicated that synthesis of lipids and
      steroids was activated in PCOS GCs. 5-Methylcytosine analysis demonstrated that
      there was an approximate 25% reduction in global DNA methylation of GCs in PCOS
      women (4.44 +/- 0.65%) compared with the controls (6.07 +/- 0.72%; P < 0.05).
      Using MassArray EpiTYPER quantitative DNA methylation analysis, we also found
      hypomethylation of several gene promoters related to lipid and steroid synthesis,
      which might result in the aberrant expression of these genes. Conclusions: Our
      results suggest that hypomethylated genes related to the synthesis of lipid and
      steroid may dysregulate expression of these genes and promote synthesis of
      steroid hormones including androgen, which could partially explain mechanisms of
      hyperandrogenism in PCOS.

PMID- 29344317
TI  - Survey of Dermatologists and Venereologists Shows Varying Approach to Penile
      Biopsies.
AB  - OBJECTIVE: To determine frequency of use and safety of epinephrine containing
      local anesthesia among dermatologists in the United Kingdom and venereologists
      undertaking penile biopsy. DESIGN: A survey was distributed nationally to members
      of the British Association of Dermatologists and the British Association for
      Sexual Health and Human Immunodeficiency Virus in December 2016. RESULTS: Sixty
      six responses were received: 36.4 percent of respondents used epinephrine
      routinely, 16.7 percent sometimes used it, and 47 percent did not use it at all.
      Epinephrine use was more commonly by dermatologists in either some or all cases
      (56.8%) compared with venereologists (40%). Only two complications were reported
      to epinephrine use. Both were temporary without report of necrosis. CONCLUSION:
      Use of epinephrine-containing local anesthesia is common among physicians in the
      United Kingdom undertaking penile biopsies. Despite this, no episodes of necrosis
      were observed. While further investigation is still required, it is likely that
      use of epinephrine-containing local anesthesia is safe for local penile
      injection.

PMID- 29344316
TI  - Clinical, Biochemical, and Hormonal Associations in Female Patients with Acne: A
      Study and Literature Review.
AB  - Female acne is often associated with clinical signs of hyperandrogenism or
      metabolic syndrome. Various hormonal and biochemical factors as well as Vitamin D
      deficiency play a role in the etiopathogenesis of acne, and it is important to be
      able to detect the altered marker(s) indicative of certain abnormalities in order
      to diagnose and treat the cause. However, interpretation of these markers can be
      difficult, as there is ambiguity as to what is considered "normal" or "abnormal."
      The aim of this study was to explore the associations that acne might have with
      certain clinical, hormonal, and biological factors among female patients with
      acne. Additionally, the available literature was reviewed in order to determine
      the prevalence of these associations, discussion of which is provided. The
      author's investigations reveal a very high prevalence of abnormal metabolic and
      hormonal statuses among women with acne, indicating the need for dermatologists
      to maintain a high index of suspician for other disorders, especially metabolic
      disorders (and in particular, polycystic ovary syndrome), when treating female
      patients with acne.

PMID- 29344318
TI  - Noninvasive Long-term Monitoring of Actinic Keratosis and Field Cancerization
      Following Treatment with Ingenol Mebutate Gel 0.015.
AB  - OBJECTIVE: To determine whether actinic keratosis and photodamaged perilesional
      areas (field cancerization) treated successfully with topical ingenol mebutate
      gel 0.015% remained clear one year later, and to treat actinic keratosis and
      perilesional skin not treated one year earlier. DESIGN: Single-center, single
      arm, open-label extension of an original clinical study completed one year
      earlier. SETTING: An outpatient clinic. PARTICIPANTS: Fifteen of the original 28
      study patients enrolled in and who completed the extension phase. MEASUREMENTS:
      All treated and untreated lesions in the original study were evaluated
      clinically, dermoscopically, and with optical coherence tomography at Day 0 of
      the extension study. Previously untreated lesions were then treated with ingenol
      mebutate gel 0.015% for three days and reevaluated at Day 60. RESULTS: There was
      no significant increase in actinic keratoses over one year. The majority of
      actinic keratoses not treated in the original study were still present at the
      beginning of the extension study. Following treatment, 69 percent of these
      lesions cleared by Day 60 of the extension study, which was not significantly
      different from the 79 percent clearance observed in the original study.
      CONCLUSION: Ingenol mebutate 0.015% maintained clearance of lesions treated one
      year earlier. Optical coherence therapy demonstrated its reliability as a
      noninvasive mode of diagnosis for actinic keratosis as well as actinic damage in
      the surrounding areas of field cancerization. Optical coherence therapy also
      showed that previously untreated lesions exhibited similar clearance rates once
      treated with the medication.

PMID- 29344319
TI  - Sandalwood Album Oil as a Botanical Therapeutic in Dermatology.
AB  - Many skin conditions and diseases are characterized by inflammation, infection,
      and hyperplasia. Safe and effective topical treatment options that can be used
      long-term are needed. Traditional botanical medicines, which are often complex
      mixtures that exert their biological activities via multiple mechanisms of
      action, are being studied as potential new active ingredients in dermatology.
      Sandalwood album oil (SAO), also known as East Indian sandalwood oil (EISO), is
      an essential oil distilled from the Santalum album tree and has demonstrated
      biological activity as an anti-inflammatory, anti-microbial, and anti
      proliferative agent. Sandalwood album oil has also shown promise in clinical
      trials for treatment of acne, psoriasis, eczema, common warts, and molluscum
      contagiosum. The favorable safety profile, ease of topical use, and recent
      availability of pharmaceutical-grade sandalwood album oil support its broader use
      as the basis of novel therapies in dermatology.

PMID- 29344320
TI  - Pyoderma Gangrenosum-associated Granulomatosis with Polyangitis: A Case Report
      and Literature Review.
AB  - Granulomatosis with polyangitis, formerly known as Wegener's granulomatosis, is a
      multi-system vasculitis that has a variable clinical presentation. Although
      uncommon, cutaneous symptoms can be the initial presenting symptom of
      granulomatosis with polyangitis. We present an unusual case of pyoderma
      gangrenosum followed by a diagnosis of granulomatosis with polyangitis. We also
      provide a review of current literature on therapeutic options.

PMID- 29344321
TI  - Fixed Drug Eruption to Supplement Containing Ginkgo Biloba and Vinpocetine: A
      Case Report and Review of Related Cutaneous Side Effects.
AB  - BACKGROUND: Fixed drug eruption is a cutaneous reaction to a systemic agent that
      typically presents as an annular or oval erythematous patch or blister and
      subsequently resolves with postinflammatory hyperpigmentation at the site. Ginkgo
      biloba leaf extract and vinpocetine are nutritional supplements used to enhance
      memory in patients with dementia and age-related memory impairment conditions
      such as Alzheimer's disease. PURPOSE: To describe a fixed drug eruption in a man
      who repeatedly developed pruritus and macular erythema on his distal penile shaft
      after ingesting a natural product containing Ginkgo biloba and vinpocetine.
      METHODS: The medical literature was retrospectively reviewed using PubMed,
      searching specifically for the terms cutaneous/skin adverse/side effects, fixed
      drug eruption, Ginkgo biloba, and vinpocetine. Patient reports and previous
      reviews of the subject were critically assessed, and the salient features of
      cutaneous adverse effects in patients receiving either Ginkgo biloba or
      vinpocetine are presented. RESULTS: Cutaneous adverse effects from Ginkgo biloba
      and vinpocetine are infrequent. Ginkgo biloba fruit can result in contact
      dermatitis (following topical exposure) and mucosal symptoms of the mouth and
      anus (following oral exposure); in addition, an erythematous maculopapular
      generalized eruption or possibly Steven-Johnson syndrome can occur after oral
      ingestion of the Ginkgo biloba leaf extract. Facial erythema has been associated
      with vinpocetine ingestion. Pruritus and an annular erythema localized to the
      distal penile shaft developed after initial and repeat ingestion of a Ginkgo
      biloba/vinpocetine product. CONCLUSION:Ginkgo biloba and vinpocetine should be
      added to the agents that can potentially cause a fixed drug eruption.

PMID- 29344323
TI  - The Impact of Quantitative Data Provided by a Multi-spectral Digital Skin Lesion
      Analysis Device on Dermatologists'Decisions to Biopsy Pigmented Lesions.
AB  - BACKGROUND: Early diagnosis of melanoma is critical to survival. New
      technologies, such as a multi-spectral digital skin lesion analysis (MSDSLA)
      device [MelaFind, STRATA Skin Sciences, Horsham, Pennsylvania] may be useful to
      enhance clinician evaluation of concerning pigmented skin lesions. Previous
      studies evaluated the effect of only the binary output. OBJECTIVE: The objective
      of this study was to determine how decisions dermatologists make regarding
      pigmented lesion biopsies are impacted by providing both the underlying
      classifier score (CS) and associated probability risk provided by multi-spectral
      digital skin lesion analysis. This outcome was also compared against the
      improvement reported with the provision of only the binary output. METHODS:
      Dermatologists attending an educational conference evaluated 50 pigmented lesions
      (25 melanomas and 25 benign lesions). Participants were asked if they would
      biopsy the lesion based on clinical images, and were asked this question again
      after being shown multi-spectral digital skin lesion analysis data that included
      the probability graphs and classifier score. RESULTS: Data were analyzed from a
      total of 160 United States board-certified dermatologists. Biopsy sensitivity for
      melanoma improved from 76 percent following clinical evaluation to 92 percent
      after quantitative multi-spectral digital skin lesion analysis information was
      provided (p<0.0001). Specificity improved from 52 percent to 79 percent
      (p<0.0001). The positive predictive value increased from 61 percent to 81 percent
      (p<0.01) when the quantitative data were provided. Negative predictive value also
      increased (68% vs. 91%, p<0.01), and overall biopsy accuracy was greater with
      multi-spectral digital skin lesion analysis (64% vs. 86%, p<0.001). Interrater
      reliability improved (intraclass correlation 0.466 before, 0.559 after).
      CONCLUSION: Incorporating the classifier score and probability data into
      physician evaluation of pigmented lesions led to both increased sensitivity and
      specificity, thereby resulting in more accurate biopsy decisions.

PMID- 29344322
TI  - Acne Scarring-Pathogenesis, Evaluation, and Treatment Options.
AB  - Acne vulgaris is a ubiquitous problem affecting 80 percent of people ages 11 to
      30 years, with many patients experiencing some degree of scarring. This review
      focuses on atrophic scars, the most common type of acne scar. We briefly address
      the cellular sequelae that lead to scar formation and the initial evaluation of
      patients with acne scars. We then discuss an algorithmic approach to the
      treatment of acne scarring based on the classification of scars into erythematous
      and atrophic types. Lastly, we discuss the future treatment of acne scars and
      ongoing clinical trials.

PMID- 29344324
TI  - Treatment of Lateral Periorbital Lines with Different Dilutions of
      IncobotulinumtoxinA.
AB  - BACKGROUND: IncobotulinumtoxinA is a botulinum neurotoxin type A that is free
      from complexing proteins and is used in various therapeutic indications and
      aesthetic medicine. It is approved for the treatment of glabellar frown lines in
      the United States. In Europe, it is also approved for the treatment of lateral
      periorbital lines (crow's feet) and for the combined treatment of upper facial
      lines, including glabellar frown lines, crow's feet, and horizontal forehead
      lines. METHODS: In the present study, incobotulinumtoxinA was injected at two
      different dilutions to treat female subjects aged 40 to 50 years who had moderate
      to-severe lateral periorbital lines at maximum contraction according to a score
      of 2 or 3 points on the 5-point Merz Aesthetics Scales (MAS). For Group 1 (n=20),
      50U of incobotulinumtoxinA were reconstituted with 1.60mL of 0.9% NaCI, and for
      Group 2 (n=20), a reconstitution volume of 0.55mL was used. RESULTS: Merz
      Aesthetics Scales scores were markedly improved by at least one point in both
      groups at one month and three months. The mean Merz Aesthetics Scales scores at
      one month were 0.4 and 0.6 points for Group 1 and Group 2, respectively,
      corresponding to a mean improvement of 2.0 and 1.8 points compared with baseline,
      respectively. CONCLUSION: No significant differences in efficacy and tolerability
      of incobotulinumtoxinA were seen between the two dilutions at any time point.

PMID- 29344325
TI  - Polycystic Ovarian Syndrome-associated Confluent and Reticulated Papillomatosis:
      Report of a Patient Successfully Treated with Azithromycin.
AB  - Polycystic ovarian syndrome is a common endocrine disorder with a variety of
      dermatologic manifestations among young women. Confluent and reticulated
      papillomatosis is a rare dermatosis of unknown etiology that is seldom reported
      in patients with polycystic ovarian syndrome. We describe the case of a young
      woman with obesity, confluent and reticulated papillomatosis, and concurrent
      acanthosis nigricans. Her history, physical examination, and laboratory
      evaluation led to the diagnosis of polycystic ovarian syndrome. The proposed
      etiologies and the various of treatment options for confluent and reticulated
      papillomatosis are discussed. In our case, the patient had a dramatic response to
      treatment with azithromycin. The etiology of confluent and reticulated
      papillomatosis remains to be established. Additionally, the mechanism behind the
      success of treatment with antibiotics is unclear; however, in this patient,
      azithromycin was a safe and effective option for the treatment of confluent and
      reticulated papillomatosis.

PMID- 29344326
TI  - Non-response to Interleukin-1 Antagonist Canakinumab in Two Patients with
      Refractory Pyoderma Gangrenosum and Hidradenitis Suppurativa.
AB  - Pyoderma gangrenosum and hidradenitis suppurativa are skin conditions
      characterized by an intense neutrophil-mediated inflammatory response that is
      often difficult to effectively treat. Successful use of interleukin (IL)-1beta
      inhibition using canakinumab and anakinra has been reported in patients with
      concomitant pyoderma gangrenosum and hidradenitis suppurativa. We report two
      cases where targeted therapy with canakinumab failed to lead to improvement for
      patients with pyoderma gangrenosum and hidradenitis suppurativa. The reason
      behind the non-response to IL-1beta blockade seen in these patients is unclear.
      Our report suggests that further controlled studies are warranted to help
      clinicians predict treatment responses to anti-IL-1 therapies in these
      challenging patients.

PMID- 29344327
TI  - Secukinumab: a review of the anti-IL-17A biologic for the treatment of psoriasis.
AB  - Psoriasis is a systemic inflammatory disease associated with numerous
      comorbidities and a profound impact on patients' quality of life. While its
      complex immune pathogenesis is still not fully delineated, current evidence
      supports a fundamental role of the T-helper-17 (TH-17) pathway and its related
      interleukin-17 (IL-17) cytokine. Thus, new antipsoriatic therapies have been
      developed to block this key cytokine and its downstream effects. Secukinumab is a
      fully humanized, monoclonal anti-IL-17A antibody, and the first in its class to
      be approved by the US Food and Drug Administration for the treatment of moderate
      to severe plaque psoriasis. It has also been approved for the treatment of active
      psoriatic arthritis and ankylosing spondylitis. Its clinical efficacy in plaque
      psoriasis has been well demonstrated in numerous phase II and III clinical
      trials. In addition, it has shown superiority in clinical trials to current
      biologic agents including etanercept and ustekinumab, with a safe adverse event
      profile. In correlation with excellent skin improvements, secukinumab is also
      associated with significant improvements in health-related quality of life
      measures. Thus, secukinumab offers the potential for equal, or improved,
      therapeutic effects compared with other biologics, and is a valuable addition to
      our current antipsoriatic armamentarium.

PMID- 29344328
TI  - Management of functional dyspepsia: state of the art and emerging therapies.
AB  - Patients with functional dyspepsia, defined in the 2016 Rome IV criteria as
      bothersome clinical dyspepsia symptoms, experience markedly reduced quality of
      life. Several etiologies have been associated with the disorder. In the Rome IV
      criteria, the brain-gut axis was acknowledged as an important factor in the
      etiology of functional gastrointestinal (GI) disorders. The distinct subgroups of
      functional dyspepsia, epigastric pain syndrome (EPS) and postprandial distress
      syndrome (PDS), are treated differently: acid secretion inhibitors are
      recommended with patients with EPS, whereas prokinetic drugs as mosapride and
      acotiamide are recommended for patients with PDS. A previous study has reported
      that proton pump inhibitors (PPIs) and H2-blockers were equally effective in
      functional dyspepsia. A new drug, acotiamide, a muscarinic antagonist and
      cholinesterase inhibitor, has been shown to improve gastric motility in rodents
      and dogs, and to reduce PDS symptoms in patients in double-blind multicenter
      studies. The pharmacological mechanisms of acotiamide remain unknown; whether
      acotiamide alters gastric emptying and gastric accommodation in patients with
      functional dyspepsia remains an open question. Other emerging treatment options
      include Rikkunshito, a herbal medicine that improves gastric emptying through 5
      hydroxytryptamine (5-HT)2B-mediated pharmacological action, and tricyclic
      antidepressants (TCAs). Different drugs are needed to accommodate the clinical
      symptoms and etiology in individual patients.

PMID- 29344329
TI  - Major adverse cardiovascular event reduction with GLP-1 and SGLT2 agents:
      evidence and clinical potential.
AB  - Treatment of patients with type 2 diabetes is directed against treating symptoms
      of hyperglycemia, minimizing the risk of hypoglycemia, and the risk of
      microvascular and macrovascular complications. The majority of patients with type
      2 diabetes die from cardiovascular or cerebrovascular disease. Future therapies
      should therefore focus on reducing cardiovascular morbidity in this high-risk
      population. Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium
      glucose co-transporter 2 inhibitors (SGLT2-i) are two drug classes with proven
      antihyperglycemic effect in type 2 diabetes. However, these drugs seem to have
      other effects such as weight reduction, low risk of hypoglycemia, and blood
      pressure reduction. Emerging evidence suggests pleiotropic effects, which
      potentially could be important in reducing cardiovascular risk. Prompted by
      regulatory authorities demanding cardiovascular outcome trials (CVOTs) assessing
      the cardiovascular safety of new antihyperglycemic drug candidates, many CVOTs
      are ongoing and a few of these are finalized. Somewhat surprising recent CVOTs in
      both drug classes have shown promising data on cardiovascular morbidity and
      mortality in patients with a very high risk of cardiovascular events. It is
      uncertain whether this is a class effect of the two drug classes, and it is yet
      unproven whether long-term cardiovascular benefits of these drugs can be
      extrapolated to populations at lower risk of cardiovascular disease. The aim of
      the present review is to give an overview of our current knowledge of the GLP-1RA
      and SGLT2-i classes, with specific focus on mechanisms of action, effects on
      cardiovascular risk factors and cardiovascular morbidity and mortality from the
      CVOTs presently available. The clinical potential of these data is discussed.

PMID- 29344330
TI  - Developments in rare bone diseases and mineral disorders.
AB  - In the last decade, there have been a number of significant advances made in the
      field of rare bone diseases. In this review, we discuss the expansion of the
      classification system for osteogenesis imperfecta (OI) and the resultant increase
      in therapeutic options available for management of OI. Bisphosphonates remain the
      most widely used intervention for OI, although the effect on fracture rate
      reduction is equivocal. We review the other therapies showing promising results,
      including denosumab, teriparatide, sclerostin, transforming growth factor beta
      inhibition and gene targeted approaches. X-linked hypophosphataemia (XLH) is the
      most common heritable form of osteomalacia and rickets caused by a mutation in
      the phosphate regulating endopeptidase gene resulting in elevated serum
      fibroblast growth factor 23 (FGF23) and decreased renal phosphate reabsorption.
      The traditional treatment is phosphate replacement. We discuss the development of
      a human anti-FGF23 antibody (KRN23) as a promising development in the treatment
      of XLH. The current management of primary hypoparathyroidism is replacement with
      calcium and active vitamin D. This can be associated with under or over
      replacement and its inherent complications. We review the use of recombinant
      parathyroid hormone (1-84), which can significantly reduce the requirements for
      calcium and vitamin D resulting in greater safety and quality of life for
      individuals with hypoparathyroidism. The use of receptor activator of nuclear
      factor kappaB ligand infusions in the treatment of a particular form of
      osteopetrosis and enzyme replacement therapy for hypophosphatasia are also
      discussed.

PMID- 29344331
TI  - The Peripheral Flicker Illusion.
AB  - A new illusion is reported. A visual object suddenly appearing on a red
      background sometimes causes an impression of flicker or double flash. In
      Experiment 1, a red, green, or blue object was presented on a red, green, blue,
      or gray background. Participants evaluated the illusion strength in reference to
      the physical flicker of a gray object presented in central vision. The results
      show that the green or blue object presented on the red background caused the
      illusion. In Experiment 2, the effect of retinal eccentricity on the illusion was
      tested. The results showed that the illusion was weak in central vision but
      became stronger as the retinal eccentricity of the objects' presentation
      increased. In Experiment 3, optimal luminance conditions for the illusion were
      explored with the green and blue objects. The illusion was strong when object
      luminance was lower than background luminance and the optimal luminance for the
      blue object was lower than that for the green object. We propose a tentative
      theory for the illusion and discuss its cause.

PMID- 29344332
TI  - Kitaoka's Tomato: Two Simple Explanations Based on Information in the Stimulus.
AB  - Kitaoka's Tomato is a color illusion in which a semitransparent blue-green field
      is placed on top of a red object (a tomato). The tomato appears red even though
      the pixels would appear green if viewed in isolation. We show that this
      phenomenon can be explained by a high-pass filter and by histogram equalization.
      The results suggest that this illusion does not require complex inferences about
      color constancy; rather, the tomato's red is available in the physical stimulus
      at the appropriate spatial scale and dynamic range.

PMID- 29344333
TI  - Inverting the Facing-the-Viewer Bias for Biological Motion Stimuli.
AB  - Depth-ambiguous point-light walkers are most frequently seen as facing-the-viewer
      (FTV). It has been argued that the FTV bias depends on recognising the stimulus
      as a person. Accordingly, reducing the social relevance of biological motion by
      presenting stimuli upside down has been shown to reduce FTV bias. Here, we
      replicated the experiment that reported this finding and added stick figure
      walkers to the task in order to assess the effect of explicit shape information
      on facing bias for inverted figures. We measured the FTV bias for upright and
      inverted stick figure walkers and point-light walkers presented in different
      azimuth orientations. Inversion of the stimuli did not reduce facing direction
      judgements to chance levels. In fact, we observed a significant facing away bias
      in the inverted stimulus conditions. In addition, we found no difference in the
      pattern of data between stick figure and point-light walkers. Although the
      results are broadly consistent with previous findings, we do not conclude that
      inverting biological motion simply negates the FTV bias; rather, inversion causes
      stimuli to be seen facing away from the viewer more often than not. The results
      support the interpretation that primarily low-level visual processes are
      responsible for the biases produced by both upright and inverted stimuli.

PMID- 29344335
TI  - Glycemic control among primary care patients with type 2 diabetes mellitus in the
      Gaza Strip, Palestine.
AB  - Aim: In this study, we aimed to assess the level of good glycemic control, to
      determine association between adherence to antidiabetic medications and
      glycosylated hemoglobin (HbA1c) and to examine factors influencing good glycemic
      control. Materials and methods: A cross-sectional design was employed among 369
      patients with type 2 diabetes mellitus (T2DM) from four Ministry of Health health
      centers in 2016. A sample of 3 ml blood was taken to measure the HbA1c, and
      patients were asked to fill out a pretested questionnaire. Univariate and
      multivariate logistic regressions, to identify independent factors associated
      with good glycemic control, were conducted using SPSS software version 22 (IBM
      Corp, Armonk, NY, USA). Results: Mean [+/-standard deviation (SD)] of HbA1c was
      8.97 (2.02) and one fifth of patients had good glycemic control (HbA1c ? 7%).
      Factors associated with good glycemic control were: older age [odds ratio (OR) =
      0.96, 95% confidence interval (CI): 0.933-0.988), high medication adherence (OR:
      2.757, 95% CI: 1.308-4.693), and better health literacy (OR= 2.124, 95% CI: 1.917
      4.921). Duration of diabetes mellitus (DM > 7 years) was inversely related to
      good glycemic control (OR = 2.255, 95% CI: 1.189-4.276). Conclusion: Our study
      showed that glycemic control was suboptimal, and factors associated with that
      were: older age, high medication adherence, and better health literacy. Knowledge
      of these factors could be an entry toward helping patients and targeting
      interventions to improve glycemic control and prevent diabetes-related
      complications.

PMID- 29344334
TI  - Collective adhesion and displacement of retinal progenitor cells upon
      extracellular matrix substrates of transplantable biomaterials.
AB  - Strategies to replace retinal photoreceptors lost to damage or disease rely upon
      the migration of replacement cells transplanted into sub-retinal spaces. A
      significant obstacle to the advancement of cell transplantation for retinal
      repair is the limited migration of transplanted cells into host retina. In this
      work, we examine the adhesion and displacement responses of retinal progenitor
      cells on extracellular matrix substrates found in retina as well as widely used
      in the design and preparation of transplantable scaffolds. The data illustrate
      that retinal progenitor cells exhibit unique adhesive and displacement dynamics
      in response to poly-l-lysine, fibronectin, laminin, hyaluronic acid, and
      Matrigel. These findings suggest that transplantable biomaterials can be designed
      to improve cell integration by incorporating extracellular matrix substrates that
      affect the migratory behaviors of replacement cells.

PMID- 29344336
TI  - Treating nonalcoholic fatty liver disease in patients with type 2 diabetes
      mellitus: a review of efficacy and safety.
AB  - Objective: To review current literature for the efficacy and safety of treatment
      for nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes
      mellitus (T2DM). Data sources: A PubMed literature search from January 1990 to
      June 2017 was conducted using the search terms nonalcoholic fatty liver disease,
      diabetes mellitus, type 2, therapy, treatment, treat, therapeutics, nonalcoholic
      fatty liver, nonalcoholic hepatosteatosis, NASH, NAFLD, metformin, and statin.
      Bibliographies of chosen articles were reviewed. Study selection and data
      extraction: Relevant articles on metformin, thiazolidinediones (TZD), glucagon
      like peptide-1 receptor agonists (GLP-1 RA), and statins for the treatment of
      NAFLD which included patients with T2DM were reviewed. A total of 23 relevant
      studies were found and included randomized controlled, observational, and open
      label designs, as well as three meta-analyses. Data synthesis: Metformin combined
      with weight loss provides a modest improvement in steatosis and no improvement in
      fibrosis in patients with NAFLD and T2DM. TZDs showed positive results on
      fibrosis and resolution of NASH but at least half of patients studied were
      nonresponders. GLP-1 RAs also showed favorable results on reductions in
      transaminases and steatosis and improvements in insulin sensitivity and weight
      loss but lack efficacy data for resolution of NASH or improvement in fibrosis
      scores. Statins showed favorable results on reductions in transaminases but mixed
      results for improvement in steatosis and fibrosis scores. Conclusion: All
      reviewed treatment options are safe for management of NAFLD in patients with T2DM
      but long-term histological improvements are minimal. TZDs are efficacious for
      resolution of NASH and improvements in fibrosis but long-term use is required to
      maintain these results.

PMID- 29344337
TI  - Financial burden of diabetic foot ulcers to world: a progressive topic to discuss
      always.
AB  - Diabetic foot complications are the most common occurring problems throughout the
      globe, resulting in devastating economic crises for the patients, families and
      society. Diabetic foot ulcers (DFUs) have a neuropathic origin with a progressive
      prevalence rate in developing countries compared with developed countries among
      diabetes mellitus patients. Diabetic patients that are of greatest risk of ulcers
      may easily be diagnosed with foot examination. Economic burden may be carefully
      examined. The budget costing must include both the clinical and social impact of
      the patients.

PMID- 29344338
TI  - Current best practice in the management of Turner syndrome.
AB  - Turner syndrome (TS) is characterized by partial or complete loss of the second X
      chromosome in phenotypic females resulting in a constellation of clinical
      findings that may include lymphedema, cardiac anomalies, short stature, primary
      ovarian failure and neurocognitive difficulties. Optimizing health care delivery
      is important to enable these individuals achieve their full potential. We review
      the current best practice management recommendations for individuals with TS
      focusing on the latest consensus opinion in regard to genetic diagnosis,
      treatment of short stature, estrogen supplementation, addressing psychosocial
      issues, as well screening for other comorbidities. A multidisciplinary approach
      and a well-planned transition to adult follow-up care will improve health care
      delivery significantly for this population.

PMID- 29344339
TI  - Clozapine discontinuation in early schizophrenia: a retrospective case note
      review of patients under an early intervention service.
AB  - Aim: Research in patients with treatment-resistant schizophrenia has demonstrated
      that clozapine discontinuation is associated with poor outcomes. There is,
      however, a paucity of research investigating the impact of clozapine
      discontinuation specifically in younger patients with more recent onset
      schizophrenia. A case note review was therefore conducted to ascertain medium
      term prognoses in patients with treatment-resistant schizophrenia under an early
      intervention service (EIS) following clozapine discontinuation. Methods: The case
      notes of 25 patients under the care of Birmingham EIS who discontinued clozapine
      were examined retrospectively. Reasons for discontinuation were recorded.
      Clinical outcomes including total duration of inpatient or home treatment
      admission, antipsychotic dose, number of alternative antipsychotics prescribed
      and adverse events were recorded for both the year before and the year after
      stopping clozapine. Statistical comparisons of pre- and post-discontinuation
      clinical outcomes determined whether discontinuation had negative effects.
      Results: There was no significant difference between the pre- and post
      discontinuation clinical status following clozapine discontinuation. More than
      half (56%) of patients remained stable after stopping clozapine. Mean inpatient
      or home treatment stay rose from 29.7 to 62.6 days (p = 0.155), total
      antipsychotic dose from 50.1% of British National Formulary (BNF) limits to 60.5%
      (p = 0.627), number of alternative antipsychotics prescribed from 1.28 to 1.80 (p
      = 0.186), number of hospital/home treatment episodes from 0.20 to 0.44 (p =
      0.083) and number of adverse events from 0 to 0.20 (p = 0.059). Non-compliance
      was the main reason for discontinuation (44%, n = 11). Conclusions: This is the
      first clozapine discontinuation study specifically considering EIS patients.
      Discontinuation did not lead to significant effects on 1 year outcomes, though
      the study is underpowered. These findings may be used to inform future
      prospective cohort discontinuation studies.

PMID- 29344340
TI  - Assessment and management of sexual dysfunction in the context of depression.
AB  - Sexual dysfunction (SD) is pervasive and underreported, and its effects on
      quality of life are underestimated. Due in part to its bidirectional relationship
      with depression, SD can be difficult to diagnose; it is also a common side effect
      of many antidepressants, leading to treatment noncompliance. While physicians
      often count on patients to spontaneously report SD, treatment is optimized when
      the clinician instead performs a thorough assessment of sexual functioning before
      and during drug therapy using a standardized questionnaire such as the Arizona
      Sexual Experiences Scale (ASEX). Separating the effects of the disorder from
      those of medications is challenging; we present a concise, evidence-based
      schematic to assist physicians in minimizing treatment-emergent sexual
      dysfunction (TESD) while treating depression. Vascular, hormonal, neurogenic, and
      pharmacological factors should be considered when a patient presents with SD. We
      also recommend that physicians obtain patient information about baseline and
      historical sexual functioning before prescribing a drug that may lead to SD and
      follow up accordingly. When the goal is to treat depression while attenuating the
      risk of sexual symptoms, physicians may wish to consider agomelatine, bupropion,
      desvenlafaxine, moclobemide, trazodone, vilazodone, and vortioxetine.

PMID- 29344341
TI  - Treatment of adult ADHD: a clinical perspective.
AB  - Adult attention deficit/hyperactivity disorder (ADHD) has moved from the blurred
      edge of clinical focus to clear recognition as a prevalent and significant
      disorder in its own right. It is a relatively common comorbidity which if
      identified and treated may open the door to better outcomes for hard-to-treat
      patients. Conversely, failure to identify and treat adult ADHD is linked to
      negative outcomes. The recognition of the importance of adult ADHD in a subset of
      our patients challenges us to overcome our anxiety about this diagnosis and
      prevent the societal marginalization of vulnerable patients. Adult ADHD responds
      well to integrated pharmacological and psychotherapeutic intervention. Its
      treatment responsiveness reduces disability and allows the comorbidity which is
      typically present to be addressed. Mastering this challenge can make the
      diagnosis and treatment of adult ADHD a rewarding experience.

PMID- 29344343
TI  - The role of selective serotonin reuptake inhibitors in preventing relapse of
      major depressive disorder.
AB  - The objective of this review was to evaluate the efficacy of selective serotonin
      reuptake inhibitors (SSRIs) and SSRIs compared with other treatment modalities in
      preventing relapse after an episode of major depressive disorder (MDD). An Ovid
      MEDLINE and PsycINFO search (from 1987 to August 2017) was conducted using the
      following terms: selective serotonin reuptake inhibitors, antidepressants,
      depression, prevention, prophylaxis, relapse and MDD. Using predefined criteria,
      two authors independently selected and reached consensus on the included studies.
      Sixteen articles met the criteria: 10 compared the relapse rate of selective
      SSRIs with placebo or other SSRIs; one discussed the effectiveness of SSRIs plus
      psychotherapy, two compared SSRI versus tricyclic antidepressants (TCAs), two
      were mainly composed of TCAs plus psychotherapy, and one compared SSRIs and
      serotonin norepinephrine reuptake inhibitors (SNRIs). According to the included
      studies, the relapse risk in adults was lower when SSRIs were combined with
      psychotherapy. Results comparing SSRIs and SNRIs were inconclusive. TCAs may be
      equally as effective as SSRIs. Atypical antidepressants (mirtazapine and St
      John's Wort) had no significant difference in efficacy and remission rates
      compared with SSRIs. Escitalopram appeared to fare better in efficacy than other
      SSRIs, owing to a higher prophylactic efficacy and lower side effects; however,
      according to the current data, this difference was not significant. To conclude,
      this review provides evidence that continuing SSRIs for 1 year reduces risk of
      MDD and relapse. Furthermore, the combination of SSRIs and cognitive behavioural
      therapy may effectively reduce relapse. Escitalopram appeared to yield better
      results and fewer side effects than did other SSRIs or SNRIs. The effectiveness
      in reducing relapse of SSRIs was similar to that of TCAs and atypical
      antidepressants.

PMID- 29344344
TI  - Acetylcholinesterase inhibitors in treatment-resistant psychotic depression.
AB  - Dopamine receptor antagonists can be effective in psychotic depression but
      response is not assured. Visual hallucinations may arise from a dysregulation of
      brain cholinergic systems and acetylcholinesterase inhibitors (AChEIs) can treat
      such hallucinations in dementia with Lewy bodies (DLB). AChEIs have been used in
      schizophrenia with some success but their efficacy and tolerability in psychotic
      depression is unclear. This striking case illustrates AChEIs specifically
      targeting multimodal hallucinations in treatment-resistant depression. To our
      knowledge it is the first case report to do so. It highlights the value of
      delineating psychopathology when considering novel interventions. This case also
      shows the idiosyncratic nature of side effects and the importance of pursuing
      different drugs within class.

PMID- 29344342
TI  - Frontotemporal dementia: latest evidence and clinical implications.
AB  - Background: Frontotemporal dementia (FTD) describes a cluster of neurocognitive
      syndromes that present with impairment of executive functioning, changes in
      behavior, and a decrease in language proficiency. FTD is the second most common
      form of dementia in those younger than 65 years and is expected to increase in
      prevalence as the population ages. This goal in our review is to describe
      advances in the understanding of neurobiological pathology, classification,
      assessment, and treatment of FTD syndromes. Methods: PubMed was searched to
      obtain reviews and studies that pertain to advancements in genetics,
      neurobiology, neuroimaging, classification, and treatment of FTD syndromes.
      Articles were chosen with a predilection to more recent preclinical/clinical
      trials and systematic reviews. Results: Recent reviews and trials indicate a
      significant advancement in the understanding of molecular and neurobiological
      clinical correlates to variants of FTD. Genetic and histopathologic markers have
      only recently been discovered in the past decade. Current therapeutic modalities
      are limited, with most studies reporting improvement in symptoms with
      nonpharmacological interventions. However, a small number of studies have
      reported improvement of behavioral symptoms with selective serotonin reuptake
      inhibitor (SSRI) treatment. Stimulants may help with disinhibition, apathy, and
      risk-taking behavior. Memantine and cholinesterase inhibitors have not
      demonstrated efficacy in ameliorating FTD symptoms. Antipsychotics have been used
      to treat agitation and psychosis, but safety concerns and side effect profiles
      limit utilization in the general FTD population. Nevertheless, recent
      breakthroughs in the understanding of FTD pathology have led to developments in
      pharmacological interventions that focus on producing treatments with autoimmune,
      genetic, and molecular targets. Conclusion: FTD is an underdiagnosed group of
      neurological syndromes comprising multiple variants with distinct neurobiological
      profiles and presentations. Recent advances suggest there is an array of
      potential novel therapeutic targets, although data concerning their effectiveness
      are still preliminary or preclinical. Further studies are required to develop
      pharmacological interventions, as there are currently no US Food and Drug
      administration approved treatments to manage FTD syndromes.

PMID- 29344345
TI  - When the drugs don't work: treatment-resistant schizophrenia, serotonin and
      serendipity.
AB  - Treatment-resistant schizophrenia is a serious clinical problem. We adopt a
      systems-level approach positing a greater role for cognitive control mechanisms
      in the development of psychotic symptoms and illustrate the clinical application
      of this via a case report of treatment-resistant patients treated successfully
      with adjunct pro-cognitive serotonergic medication.

PMID- 29344346
TI  - Characterization and selective incorporation of small non-coding RNAs in non
      small cell lung cancer extracellular vesicles.
AB  - Background: Extracellular vesicles (EVs) play important roles in intercellular
      communication through the delivery of their cargoes, which include proteins,
      lipids, and RNAs. Increasingly, multiple studies have reported the association
      between EV small non-coding RNAs and cancer, due to their regulatory functions in
      gene expression. Hence, analysis of the features of small non-coding RNA
      expression and their incorporation into EVs is important for cancer research.
      Results: We performed deep sequencing to investigate the expression of small RNAs
      in plasma EVs from lung adenocarcinoma (ADC) patients, lung squamous cell
      carcinoma (SQCC) patients, and healthy controls. Then, eighteen differently
      expressed miRNAs in plasma EVs was validated by QRT-PCR. The small RNA expression
      profiles of plasma EVs were different among lung ADC, SQCC patients, and healthy
      controls. And many small RNAs, including 5' YRNA hY4-derived fragments, miR-451a,
      miR-122-5p, miR-20a-5p, miR-20b-5p, miR-30b-5p, and miR-665, were significantly
      upregulated in non-small cell lung cancer (NSCLC) EVs. And the cell viability
      assays indicated that hY4-derived fragments inhibited the proliferation of lung
      cancer cell A549. By comparing the cellular and EV expression levels of six
      miRNAs in NSCLC cells, we found that miR-451a and miR-122-5p were significantly
      downregulated in NSCLC cell lysates, while significantly upregulated in NSCLC
      EVs. Conclusions: The differently expressed EV small RNAs may serve as potential
      circulating biomarkers for the diagnosis of NSCLC. Particularly, YRNA hY4-derived
      fragments can serve as a novel class of biomarkers, which function as tumor
      suppressors in NSCLC. Additionally, miR-451a and miR-122-5p may be sorted into
      NSCLC EVs in a selective manner.

PMID- 29333228
TI  - Quantification of polysaccharides fixed to Gram stained slides using lactophenol
      cotton blue and digital image processing.
AB  - Indigo rings and circles emerged when I added the non-specific polysaccharide
      stain lactophenol cotton blue to Gram stained slides. I attribute the dark blue
      staining to the presence of capsular polysaccharides and bacterial slime
      associated with clumps of Gram-negative bacteria.  Since all bacterial cells are
      glycosylated and concentrate polysaccharides from the media, the majority of
      cells stain light blue. The contrast between dark and light staining is
      sufficient to enable a digital image processing thresholding technique to be
      quantitative with little background noise. Prior to the addition of lactophenol
      cotton blue, the Gram-stained slides appeared unremarkable, lacking ubiquitous
      clumps or stained polysaccharides.  Adding lactophenol cotton blue to Gram
      stained slides is a quick and inexpensive way to screen cell cultures for
      bacterial slime, clumps and biofilms that are invisible using the Gram stain
      alone.

PMID- 29344347
TI  - Epigenetic alterations in TRAMP mice: epigenome DNA methylation profiling using
      MeDIP-seq.
AB  - Purpose: We investigated the genomic DNA methylation profile of prostate cancer
      in transgenic adenocarcinoma of the mouse prostate (TRAMP) cancer model and to
      analyze the crosstalk among targeted genes and the related functional pathways.
      Methods: Prostate DNA samples from 24-week-old TRAMP and C57BL/6 male mice were
      isolated. The DNA methylation profiles were analyzed by methylated DNA
      immunoprecipitation (MeDIP) followed by next-generation sequencing (MeDIP-seq).
      Canonical pathways, diseases and function and network analyses of the different
      samples were then performed using the Ingenuity(r) Pathway Analysis (IPA)
      software. Some target genes with significant difference in methylation were
      selected for validation using methylation specific primers (MSP) and qPCR.
      Results: TRAMP mice undergo extensive aberrant CpG hyper- and hypo-methylation.
      There were 2147 genes with a significant (log2-change >= 2) change in CpG
      methylation between the two groups, as mapped by the IPA software. Among these
      genes, the methylation of 1105 and 1042 genes was significantly decreased and
      increased, respectively, in TRAMP prostate tumors. The top associated disease
      identified by IPA was adenocarcinoma; however, the cAMP response element-binding
      protein (CREB)-, histone deacetylase 2 (HDAC2)-, glutathione S-transferase pi
      (GSTP1)- and polyubiquitin-C (UBC)-related pathways showed significantly altered
      methylation profiles based on the canonical pathway and network analyses. MSP and
      qPCR results of genes of interests corroborated with MeDIP-seq findings.
      Conclusions: This is the first MeDIP-seq with IPA analysis of the TRAMP model to
      provide novel insight into the genome-wide methylation profile of prostate
      cancer. Studies on epigenetics, such as DNA methylation, will potentially provide
      novel avenues and strategies for further development of biomarkers targeted for
      treatment and prevention approaches for prostate cancer.

PMID- 29333229
TI  - Predicted protein interactions of IFITMs may shed light on mechanisms of Zika
      virus-induced microcephaly and host invasion.
AB  - After the first reported case of Zika virus (ZIKV) in Brazil, in 2015, a
      significant increase in the reported cases of microcephaly was observed.
      Microcephaly is a neurological condition in which the infant's head is
      significantly smaller with complications in brain development. Recently, two
      small membrane-associated interferon-inducible transmembrane proteins (IFITM1 and
      IFITM3) have been shown to repress members of the flaviviridae family which
      includes ZIKV. However, the exact mechanisms leading to the inhibition of the
      virus are yet unknown. Here, we assembled an interactome of IFITM1 and IFITM3
      with known protein-protein interactions (PPIs) collected from publicly available
      databases and novel PPIs predicted using the High-confidence Protein-Protein
      Interaction Prediction (HiPPIP) model. We analyzed the functional and pathway
      associations of the interacting proteins, and found that there are several
      immunity pathways (toll-like receptor signaling, cd28 signaling in T-helper
      cells, crosstalk between dendritic cells and natural killer cells), neuronal
      pathways (axonal guidance signaling, neural tube closure and actin cytoskeleton
      signaling) and developmental pathways (neural tube closure, embryonic skeletal
      system development) that are associated with these interactors. Our novel PPIs
      associate cilia dysfunction in ependymal cells to microcephaly, and may also shed
      light on potential targets of ZIKV for host invasion by immunosuppression and
      cytoskeletal rearrangements. These results could help direct future research in
      elucidating the mechanisms underlying host defense to ZIKV and other
      flaviviruses.

PMID- 29344350
TI  - The sensitivity of the human thirst response to changes in plasma osmolality: a
      systematic review.
AB  - Background: Dehydration is highly prevalent and is associated with adverse
      cardiovascular and renal events. Clinical assessment of dehydration lacks
      sensitivity. Perhaps a patient's thirst can provide an accurate guide to fluid
      therapy. This systematic review examines the sensitivity of thirst in responding
      to changes in plasma osmolality in participants of any age with no condition
      directly effecting their sense of thirst. Methods: Medline and EMBASE were
      searched up to June 2017. Inclusion criteria were all studies reporting the
      plasma osmolality threshold for the sensation of thirst. Results: A total of 12
      trials were included that assessed thirst intensity on a visual analogue scale,
      as a function of plasma osmolality (pOsm), and employed linear regression to
      define the thirst threshold. This included 167 participants, both healthy
      controls and those with a range of pathologies, with a mean age of 41 (20-78)
      years.The value +/-95% CI for the pOsm threshold for thirst sensation was found
      to be 285.23 +/- 1.29 mOsm/kg. Above this threshold, thirst intensity as a
      function of pOsm had a mean +/- SEM slope of 0.54 +/- 0.07 cm/mOsm/kg. The mean
      +/- 95% CI vasopressin release threshold was very similar to that of thirst,
      being 284.3 +/- 0.71 mOsm/kg.Heterogeneity across studies can be accounted for by
      subtle variation in experimental protocol and data handling. Conclusion: The
      thresholds for thirst activation and vasopressin release lie in the middle of the
      normal range of plasma osmolality. Thirst increases linearly as pOsm rises. Thus,
      osmotically balanced fluid administered as per a patient's sensation of thirst
      should result in a plasma osmolality within the normal range. This work received
      no funding.

PMID- 29344351
TI  - Endemic carbapenem-nonsusceptible Acinetobacter baumannii-calcoaceticus complex
      in intensive care units of the national referral hospital in Jakarta, Indonesia.
AB  - Background: Carbapenem-nonsusceptible A. baumannii-calcoaceticus complex have
      emerged worldwide, but the epidemiology in Indonesian hospitals has not been
      studied. Methods: A prospective observational study was performed on the
      intensive care units (ICUs) of the national referral hospital in Jakarta
      Indonesia, in 2013 and 2014. All consecutive adult patients admitted and
      hospitalized for >48 h in ICUs were included. Basic and clinical data at
      admission were recorded. Carbapenem-nonsusceptible A. baumannii-calcoaceticus
      complex from clinical cultures and standardized screening were included.
      Environmental niches and healthcare workers (HCWs) were also screened. PCR was
      used to detect carbapenemase genes, and Raman spectroscopy as well as multilocus
      sequence typing (MLST) for typing. Results: Of 412 included patients, 69 (16.7%)
      carried carbapenem-nonsusceptible A. baumannii-calcoaceticus complex on
      admission, and 89 (25.9%) became positive during ICU stay. The acquisition rate
      was 43 per 1000 patient-days at risk. Six isolates were cultured from environment
      and one from a HCW. Acquisition of carbapenem-nonsusceptible A. baumannii
      calcoaceticus complex was associated with longer ICU stay (median interquartile
      range [IQR]: 11 days [5-18], adjusted hazard ratio [aHR]: 2.56 [99% confidence
      interval (CI):1.76-3.70]), but not with mortality (adjusted odds ratio: 1.59
      [99%CI: 0.74-3.40] at the chosen level of significance). The blaOXA-23-like gene
      was detected in 292/318 (91.8%) isolates, including isolates from the environment
      and HCW. Typing revealed five major clusters. Sequence types (ST)195, ST208,
      ST218, ST642 as well as new STs were found. The dominant clone consisted of
      isolates from patients and environment throughout the study period. Conclusions:
      Carbapenem-nonsusceptible A. baumannii-calcoaceticus complex are endemic in this
      setting. Prevention requires source control and limiting transmission of strains.
      Trial registration: The study was retrospectively registered at
      www.trialregister.nl (No:5541). Candidate number: 23,527, NTR number: NTR5541,
      Date registered NTR: 22nd December 2015.

PMID- 29344352
TI  - The use of feed-grade amino acids in lactating sow diets.
AB  - Background: The use of feed grade amino acids can reduce the cost of lactation
      feed. With changing genetics, increasing feed costs, and higher number of pigs
      weaned with heavier wean weights further evaluation of higher inclusion levels of
      feed-grade amino acid in lactation diets than previously published is warranted.
      Two experiments (Exp.) were conducted to determine the optimal inclusion level of
      L-lysine HCl to be included in swine lactation diets while digestible lysine
      levels remain constant across dietary treatments and allowing feed grade amino
      acids to be added to the diet to maintain dietary ratios relative to lysine to
      maximize litter growth rate and sow reproductive performance. Furthermore, the
      studies were to evaluate minimal amino acid ratios relative to lysine that allows
      for optimal litter growth rate and sow reproductive performance. Results: Exp. 1:
      Increasing L-lysine HCl resulted in similar gilt feed intake, litter, and
      reproductive performance. Average litter gain from birth to weaning was 2.51,
      2.49, 2.59, 2.43, and 2.65 kg/d when gilts were fed 0.00, 0.075, 0.150, 0.225,
      and 0.30% L-lysine HCl, respectively. Exp. 2: The average litter gain from birth
      to weaning was 2.68, 2.73, 2.67, 2.70, and 2.64 kg/d (P < 0.70) when sows were
      fed 0.1, 0.2, 0.3, 0.4, and 0.4% L-lysine HCl plus valine, respectively. No other
      differences among dietary treatments were observed. Conclusions: Collectively,
      these studies demonstrate corn-soybean meal based lactation diets formulated with
      a constant SID lysine content for all parities containing up to 0.40% L-lysine
      HCl with only supplemental feed grade threonine and a methionine source have no
      detrimental effect on litter growth rate and subsequent total born.

PMID- 29344353
TI  - Effects of TNF receptor blockade on in vitro cell survival and response to
      negative energy balance in dairy cattle.
AB  - Background: Associative data and some controlled studies suggest that the
      inflammatory cytokine tumor necrosis factor (TNF) alpha can induce fatty liver in
      dairy cattle. However, research demonstrating that TNFalpha is a necessary
      component in the etiology of bovine fatty liver is lacking. The aim of this work
      was to evaluate whether blocking TNFalpha signaling with a synthetic cyclic
      peptide (TNF receptor loop peptide; TRLP) would improve liver metabolic function
      and reduce triglyceride accumulation during feed restriction. Results: Capability
      of TRLP to inhibit TNFalpha signaling was confirmed on primary bovine hepatocytes
      treated with recombinant bovine TNFalpha and 4 doses of TRLP (0, 1, 10, 50
      MUmol/L) over 24 h. Next, 4 lactating Holstein cows (parity 1.4 +/- 0.5, 433 +/-
      131 d in milk) in an incomplete Latin rectangle design (3 * 2) were
      subcutaneously administered with different TRLP doses (0, 1.5, 3.0 mg/kg BW)
      every 4 h for 24 h, followed by an intravenous injection of TNFalpha (5 MUg/kg
      BW). Before and for 2 h after TNFalpha injection, TRLP decreased plasma non
      esterified fatty acid (NEFA) concentration (P <= 0.05), suggesting an altered
      metabolic response to inflammation. Finally, 10 non-pregnant, non-lactating
      Holstein cows (3.9 +/- 1.1 yr of age) were randomly assigned to treatments:
      control (carrier: 57% DMSO in PBS) or TRLP (1.75 mg TRLP /kg BW per day).
      Treatments were administrated every 4 h for 7 d by subcutaneous injection to feed
      restricted cows fed 30% of maintenance energy requirements. Daily blood samples
      were analyzed for glucose, insulin, beta-hydroxybutyrate, NEFA, and haptoglobin
      concentrations, with no treatment effects detected. On d 7, cows completed a
      glucose tolerance test (GTT) by i.v. administration of a dextrose bolus (300 mg
      glucose/kg BW). Glucose, insulin, and NEFA responses failed to demonstrate any
      significant effect of treatment during the GTT. However, plasma and liver
      analyses were not indicative of dramatic lipolysis or hepatic lipidosis,
      suggesting that the feed restriction protocol failed to induce the metabolic
      state of interest. Injection site inflammation, assessed by a scorer blinded to
      treatment, was enhanced by TRLP compared to control. Conclusions: Although the
      TRLP inhibited bovine TNFalpha signaling and altered responses to i.v.
      administration of TNFalpha, repeated use over 7 d caused apparent local allergic
      responses and it failed to alter metabolism during a feed restriction-induced
      negative energy balance. Although responses to feed restriction seemed atypical
      in this study, side effects of TRLP argue against its future use as a tool for
      investigating the role of inflammation in metabolic impacts of negative energy
      balance.

PMID- 29344354
TI  - A study on the implementation fidelity of the performance-based financing policy
      in Burkina Faso after 12 months.
AB  - Background: Performance-based financing (PBF) in the health sector has recently
      gained momentum in low- and middle-income countries (LMICs) as one of the ways
      forward for achieving Universal Health Coverage. The major principle underlying
      PBF is that health centers are remunerated based on the quantity and quality of
      services they provide. PBF has been operating in Burkina Faso since 2011, and as
      a pilot project since 2014 in 15 health districts randomly assigned into four
      different models, before an eventual scale-up. Despite the need for expeditious
      documentation of the impact of PBF, caution is advised to avoid adopting hasty
      conclusions. Above all, it is crucial to understand why and how an impact is
      produced or not. Our implementation fidelity study approached this inquiry by
      comparing, after 12 months of operation, the activities implemented against what
      was planned initially and will make it possible later to establish links with the
      policy's impacts. Methods: Our study compared, in 21 health centers from three
      health districts, the implementation of activities that were core to the process
      in terms of content, coverage, and temporality. Data were collected through
      document analysis, as well as from individual interviews and focus groups with
      key informants. Results: In the first year of implementation, solid foundations
      were put in place for the intervention. Even so, implementation deficiencies and
      delays were observed with respect to certain performance auditing procedures, as
      well as in payments of PBF subsidies, which compromised the incentive-based
      rationale to some extent. Conclusion: Over next months, efforts should be made to
      adjust the intervention more closely to context and to the original planning.

PMID- 29344355
TI  - Impact of an antifungal stewardship intervention on optimization of candidemia
      management.
AB  - Background: Candidemia represents a leading cause of healthcare-associated
      bloodstream infections with significant morbidity and mortality. Previous studies
      have demonstrated that comprehensive care bundles improve candidemia management
      but are time-consuming. Objective: To determine the impact of a one-time targeted
      candidemia intervention on time to initiation of adequate therapy compared to
      standard of care. Methods: This Institutional Review Board (IRB)-approved, quasi
      experiment evaluated a targeted candidemia intervention involving a single phone
      call to the primary team providing recommendations for care. Daily follow-up was
      provided by the infectious diseases (ID) consult service. Two time periods were
      evaluated: pre-intervention (01 August 2012 to 31 July 2014) and post
      intervention (01 October 2014 to 30 September 2016). The primary endpoint was
      time to adequate antifungal therapy (TTx) in the business hours (6 a.m. to 6 p.m.
      Monday through Friday) population (BHP). Secondary endpoints were TTx in the
      total population as well as infection-related length of stay (IF-LOS) and
      compliance with quality indicators (composite endpoint: ophthalmology (OPH)
      consult, repeat cultures, and ?14 days of adequate therapy). Results: In all, 117
      patients were included (pre-intervention = 50, post-intervention = 67, BHP = 51).
      TTx decreased from 2 h 57 m to 2 h 12 m (p = 0.094) in the BHP and 3 h 30 m to 2
      h 9 m (p = 0.021) in the total population. There was no difference in IF-LOS (p =
      0.797), compliance with quality indicators (p = 0.343), or in-hospital mortality
      (p = 0.761). Post-intervention, there were more ID and OPH consults (p < 0.001).
      Conclusions: Our one-time candidemia intervention did not statistically decrease
      time to adequate therapy in the BHP, but did in the total population. No
      differences were found for other clinical outcomes, except increases in ID and
      OPH consults. Further studies are needed to examine whether a one-time
      intervention is non-inferior to a more comprehensive care bundle.

PMID- 29344356
TI  - Risk factors and outcomes for multidrug-resistant Gram-negative bacilli
      bacteremia.
AB  - Background: The incidence of multidrug-resistant (MDR) organisms is increasing
      along with mortality. Identifying risk factors for the development of MDR Gram
      negative bacilli (GNB) bacteremia could greatly impact patient care and
      management. Methods: Data from the electronic health record of patients with GNB
      over 13-month period were collected at a single university medical center.
      Baseline demographic data, risk factor, microbiological data, recurrence of
      bacteremia, and mortality were recorded. Results: A total of 177 patients were
      included in the analysis. MDR GNB occurred in 46 patients (26%). The mortality
      rate in the MDR group was 34.8% compared to 13.7% in non-MDR group (p = 0.002).
      In multivariate analysis, diabetes mellitus [DM; odds ratio (OR): 2.8, 95%
      confidence interval (CI): 1-4.88], previous antibiotic use (OR: 2.93, 95% CI:
      1.25-6.87), and urinary catheter as a source of infection (OR 5.96, 95% CI: 1.78
      19.94) were significant risk factors for the development of MDR GNB. In addition,
      end-stage liver disease (OR: 3.64, 95% CI: 1.07-12.3), solid organ malignancy
      (OR: 3.64, 95% CI: 1.25-10.56), intra-abdominal source of infection (OR: 3.66,
      95% CI: 1.14-11.73), inappropriate empiric antibiotics (OR 7.59, 95% CI: 1.68
      34.34) and urinary catheter as a source of infection (OR 5.68, 95% CI: 1.37-23.5)
      were significant factors for mortality in patients with MDR GNB. Conclusion: Our
      study provides important information about the risk factors for the development
      of MDR GNB bacteremia and helps prognosticate patient with MDR GNB.

PMID- 29344357
TI  - Examining the effectiveness of a cognitive intervention to improve cognitive
      function in a population of older adults living with HIV: a pilot study.
AB  - Objective: The purpose of this randomized-controlled pilot study was to explore
      the effectiveness of a home-based computerized cognitive training intervention in
      improving cognitive function in a population of older adults with mild cognitive
      impairment who are living with HIV. Methods: In all, 24 participants were
      enrolled in this study. All study participants were impaired [defined as Montreal
      Cognitive Assessment (MoCA) score < 26]; 12 were randomly assigned to a computer
      training intervention group and 12 to a control group. The intervention group
      used a home-based computerized cognitive training program for 8 weeks, while the
      control group received health-related newsletter via email and follow-up phone
      calls. Cognitive function was measured at study entry, immediately post
      intervention, and 8 and 16 weeks post intervention. Results: This study achieved
      a 92% retention rate, losing two persons from the intervention group.
      Participants in the intervention group scored significantly higher on cognitive
      testing immediately post intervention compared to the control group: F(1, 19) =
      4.92, p = 0.04. The partial Eta squared of 0.32 indicates a small to moderate
      effect size. Discussion: Cognitive improvement was seen immediately after the
      intervention, and cognitive improvement was still evident 16 weeks post
      intervention. Cognitive training could be considered as an option for older
      adults with HIV experiencing mild cognitive impairment.

PMID- 29344359
TI  - Group schema therapy for eating disorders: study protocol.
AB  - Background: The treatment of eating disorders is a difficult endeavor, with only
      a relatively small proportion of clients responding to and completing standard
      cognitive behavioural therapy (CBT). Given the prevalence of co-morbidity and
      complex personality traits in this population, Schema Therapy has been identified
      as a potentially viable treatment option. A case series of Group Schema Therapy
      for Eating Disorders (ST-E-g) yielded positive findings and the study protocol
      outlined in this article aims to extend upon these preliminary findings to
      evaluate group Schema Therapy for eating disorders in a larger sample (n = 40).
      Methods/design: Participants undergo a two-hour assessment where they complete a
      number of standard questionnaires and their diagnostic status is ascertained
      using the Eating Disorder Examination. Participants then commence treatment,
      which consists of 25 weekly group sessions lasting for 1.5 h and four individual
      sessions. Each group consists of five to eight participants and is facilitated by
      two therapists, at least one of who is a registered psychologist trained on
      schema therapy. The primary outcome in this study is eating disorder symptom
      severity. Secondary outcomes include: cognitive schemas, self-objectification,
      general quality of life, self-compassion, schema mode presentations, and
      Personality Disorder features. Participants complete psychological measures and
      questionnaires at pre, post, six-month and 1-year follow-up. Discussion: This
      study will expand upon preliminary research into the efficacy of group Schema
      Therapy for individuals with eating disorders. If group Schema Therapy is shown
      to reduce eating disorder symptoms, it will hold considerable promise as an
      intervention option for a group of disorders that is typically difficult to
      treat. Trial registration: ACTRN12615001323516. Registered: 2/12/2015
      (retrospectively registered, still recruiting).

PMID- 29344358
TI  - The global problem of childhood diarrhoeal diseases: emerging strategies in
      prevention and management.
AB  - Acute diarrhoeal diseases remain a leading cause of global morbidity and
      mortality particularly among young children in resource-limited countries. Recent
      large studies utilizing case-control design, prospective sampling and more
      sensitive and broad diagnostic techniques have shed light on particular pathogens
      of importance and highlighted the previously under recognized impact of these
      infections on post-acute illness mortality and growth. Vaccination, particularly
      against rotavirus, has emerged as a key effective means of preventing significant
      morbidity and mortality from childhood diarrhoeal disease. Other candidate
      vaccines against leading diarrhoeal pathogens, such as enterotoxigenic
      Escherichia coli and Shigella spp., also hold significant promise in further
      ameliorating the burden of enteric infections in children. Large studies are also
      currently underway evaluating novel and potential easy-to-implement water,
      sanitation and hygiene (WASH) preventive strategies. Given the ongoing global
      burden of this illness, the paucity of new advances in case management over the
      last several decades remains a challenge. The increasing recognition of post
      acute illness mortality and growth impairment has highlighted the need for
      interventions that go beyond management of dehydration and electrolyte
      disturbances. The few trials of novel promising interventions such as probiotics
      have mainly been conducted in high-income settings. Trials of antimicrobials have
      also been primarily conducted in high-income settings or in travellers from high
      income settings. Bloody diarrhoea has been shown to be a poor marker of
      potentially treatable bacterial enteritis, and rising antimicrobial resistance
      has also made empiric antimicrobial therapy more challenging in many settings.
      Novel effective and sustainable interventions and diagnostic strategies are
      clearly needed to help improve case management. Diarrhoeal disease and other
      enteric infections remain an unmet challenge in global child health. Most
      promising recent developments have been focused around preventive measures, in
      particular vaccination. Further advances in prevention and case management
      including the possible use of targeted antimicrobial treatment are also required
      to fully address this critical burden on child health and human potential.

PMID- 29344360
TI  - Validity, reliability and Norwegian adaptation of the Stroke-Specific Quality of
      Life (SS-QOL) scale.
AB  - Background: There is a paucity of stroke-specific instruments to assess health
      related quality of life in the Norwegian language. The objective was to examine
      the validity and reliability of a Norwegian version of the 12-domain Stroke
      Specific Quality of Life scale. Methods: A total of 125 stroke survivors were
      prospectively recruited. Questionnaires were administered at 3 months; 36 test
      retests were performed at 12 months post stroke. The translation was conducted
      according to guidelines. The internal consistency was assessed with Cronbach's
      alpha; convergent validity, with item-to-subscale correlations; and test-retest,
      with Spearman's correlations. Scaling validity was explored by calculating both
      floor and ceiling effects. A priori hypotheses regarding the associations between
      the Stroke-Specific Quality of Life domain scores and scores of established
      measures were tested. Standard error of measurement was assessed. Results: The
      Norwegian version revealed no major changes in back translations. The internal
      consistency values of the domains were Cronbach's alpha = 0.79-0.93. Rates of
      missing items were small, and the item-to-subscale correlation coefficients
      supported convergent validity (0.48-0.87). The observed floor effects were
      generally small, whereas the ceiling effects had moderate or high values (16%
      63%). Test-retest reliability indicated stability in most domains, with
      Spearman's rho = 0.67-0.94 (all p < 0.001), whereas the rho was 0.35 (p < 0.05)
      for the 'Vision' domain. Hypothesis testing supported the construct validity of
      the scale. Standard error of measurement values for each domain were generated to
      indicate the required magnitudes of detectable change. Conclusions: The Norwegian
      version of the Stroke-Specific Quality of Life scale is a reliable and valid
      instrument with good psychometric properties. It is suited for use in health
      research as well as in individual assessments of persons with stroke.

PMID- 29344361
TI  - Platelet protein biomarker panel for ovarian cancer diagnosis.
AB  - Background: Platelets support cancer growth and spread making platelet proteins
      candidates in the search for biomarkers. Methods: Two-dimensional (2D) gel
      electrophoresis, Partial Least Squares Discriminant Analysis (PLS-DA), Western
      blot, DigiWest. Results: PLS-DA of platelet protein expression in 2D gels
      suggested differences between the International Federation of Gynaecology and
      Obstetrics (FIGO) stages III-IV of ovarian cancer, compared to benign adnexal
      lesions with a sensitivity of 96% and a specificity of 88%. A PLS-DA-based model
      correctly predicted 7 out of 8 cases of FIGO stages I-II of ovarian cancer after
      verification by western blot. Receiver-operator curve (ROC) analysis indicated a
      sensitivity of 83% and specificity of 76% at cut-off >0.5 (area under the curve
      (AUC) = 0.831, p < 0.0001) for detecting these cases. Validation on an
      independent set of samples by DigiWest with PLS-DA differentiated benign adnexal
      lesions and ovarian cancer, FIGO stages III-IV, with a sensitivity of 70% and a
      specificity of 83%. Conclusion: We identified a group of platelet protein
      biomarker candidates that can quantify the differential expression between
      ovarian cancer cases as compared to benign adnexal lesions.

PMID- 29344362
TI  - Development of biomarker combinations for postoperative acute kidney injury via
      Bayesian model selection in a multicenter cohort study.
AB  - Background: Acute kidney injury (AKI) is a frequent complication of cardiac
      surgery. We sought prognostic combinations of postoperative biomarkers measured
      within 6 h of surgery, potentially in combination with cardiopulmonary bypass
      time (to account for the degree of insult to the kidney). We used data from a
      large cohort of patients and adapted methods for developing biomarker
      combinations to account for the multicenter design of the study. Methods: The
      primary endpoint was sustained mild AKI, defined as an increase of 50% or more in
      serum creatinine over preoperative levels lasting at least 2 days during the
      hospital stay. Severe AKI (secondary endpoint) was defined as a serum creatinine
      increase of 100% or more or dialysis during hospitalization. Data were from a
      cohort of 1219 adults undergoing cardiac surgery at 6 medical centers; among
      these, 117 developed sustained mild AKI and 60 developed severe AKI. We
      considered cardiopulmonary bypass time and 22 biomarkers as candidate predictors.
      We adapted Bayesian model averaging methods to develop center-adjusted
      combinations for sustained mild AKI by (1) maximizing the posterior model
      probability and (2) retaining predictors with posterior variable probabilities
      above 0.5. We used resampling-based methods to avoid optimistic bias in
      evaluating the biomarker combinations. Results: The maximum posterior model
      probability combination included plasma N-terminal-pro-B-type natriuretic
      peptide, plasma heart-type fatty acid binding protein, and change in serum
      creatinine from before to 0-6 h after surgery; the median probability combination
      additionally included plasma interleukin-6. The center-adjusted, optimism
      corrected AUCs for these combinations were 0.80 (95% CI: 0.78, 0.87) and 0.81
      (0.78, 0.87), respectively, for predicting sustained mild AKI, and 0.81 (0.76,
      0.90) and 0.83 (0.76, 0.90), respectively, for predicting severe AKI. For these
      data, the Bayesian model averaging methods yielded combinations with prognostic
      capacity comparable to that achieved by standard frequentist methods but with
      more parsimonious models. Conclusions: Pending external validation, the
      identified combinations could be used to identify individuals at high risk of AKI
      immediately after cardiac surgery and could facilitate clinical trials of
      renoprotective agents.

PMID- 29344363
TI  - Motile Salmonella serotypes causing high mortality in poultry farms in three
      South-Western States of Nigeria.
AB  - This study was carried out to identify the Salmonella serotypes causing high
      mortality in chickens in Lagos, Ogun and Oyo states, Nigeria. Chickens presented
      for postmortem examination during disease outbreaks that were characterised by
      high mortality (40 per cent to 80 per cent) in poultry farms in the study area
      were examined from January to December, 2013. Samples of the lungs, heart, liver,
      spleen, kidneys, proventriculus, intestine and caecum were collected from
      suspected cases of salmonellosis, for bacterial culture and identification.
      Salmonella isolates were confirmed using PCR and serotyped using the Kauffman
      White scheme. Twenty-six day-old pullets were raised to two weeks and inoculated
      orally with 0.2 mL of 1*108 colony forming units of Salmonella Zega identified in
      the present study to determine their pathogenicity, while another 26 served as
      control. The Salmonella serotypes were S Zega (n=13; 35.14 per cent), Salmonella
      Kentucky (n=9; 24.32 per cent), Salmonella Herston (n=6; 16.22 per cent),
      Salmonella Nima (n=4; 10.81 per cent), Salmonella Telelkebir (n=3; 8.11 per
      cent), Salmonella Colindale (n=1; 2.70 per cent) and Salmonella Tshiongwe (n=1;
      2.70 per cent). Clinical signs in both natural and experimental infections were
      acute (70 per cent) and chronic (30 per cent), and included weakness, anorexia,
      yellowish diarrhoea, pasted vents, somnolescence and mortality, while gross
      lesions showed marked pulmonary congestion and oedema, necrotic foci in the
      myocardium; the liver, spleen and kidneys were markedly enlarged and had
      subcapsular multifocal necrosis. There were catarrhal proventriculitis and
      enteritis, and haemorrhagic typhlitis. While most of the serotypes identified in
      the present study have been isolated from poultry sources from commercial farms
      in Nigeria, to the best of the authors' knowledge, they have not been previously
      reported to cause high mortality in chickens in the study area.

PMID- 29344364
TI  - Novel dry cryotherapy system for cooling the equine digit.
AB  - Objectives: Digital cryotherapy is commonly used for laminitis prophylaxis and
      treatment. Currently validated methods for distal limb cryotherapy involve wet
      application or compression technology. There is a need for a practical,
      affordable, dry cryotherapy method that effectively cools the digit. The
      objective of this study was to evaluate the hoof wall surface temperatures
      (HWSTs) achieved with a novel dry cryotherapy technology. Design: Repeated
      measures in vivo experimental study. Setting: Experimental intervention at a
      single site. Participants: 6 systemically healthy horses (3 mares, 3 geldings).
      Interventions: Cryotherapy was applied to six horses for eight hours with a
      commercially available rubber and rubber and welded fabricice boot, which
      extended proximally to include the foot and pastern. Reusable malleable cold
      therapy packs were secured against the foot and pastern with the three built-in
      hook-and-loop fastener panels. Primary and secondary outcome measures: HWST and
      pastern surface temperature of the cryotherapy-treated limb, HWST of the control
      limb and ambient temperature were recorded every five minutes throughout the
      study period. Results: Results were analysed with mixed-effects multivariable
      regression analysis. The HWST (median 11.1 degrees C, interquartile range 8.6
      degrees C-14.7 degrees C) in the cryotherapy-treated limb was significantly
      decreased compared with the control limb (median 29.7 degrees C, interquartile
      range 28.9 degrees C-30.4 degrees C) (P<=0.001). Cryotherapy limb HWST reached a
      minimum of 6.75 degrees C (median) with an interquartile range of 4.1 degrees C
      9.3 degrees C. Minimum HWST was achieved 68 minutes after cryotherapy pack
      application. Conclusions: Dry application of cryotherapy significantly reduced
      HWST and reached minimums below the therapeutic target of 10 degrees C. This
      cryotherapy method might offer an effective alternative for digital cooling.

PMID- 29344365
TI  - Arterial pathophysiology and comparison of two devices for pulse wave velocity
      assessment in elderly men: the British regional heart study.
AB  - Objective: Vascular disease is highly prevalent in the elderly. This study aimed
      to evaluate arterial phenotype in elderly men and compare carotid-femoral pulse
      wave velocity (cfPWV) assessed by two techniques (Sphygmocor (S)and Vicorder
      (V)). Methods: 1722 men (72-92 years), participants in the British Regional Heart
      Study, underwent ultrasound assessment of carotid intima-media thickness (cIMT),
      carotid distensibility coefficient and presence of carotid plaque. cfPWV and
      ankle brachial pressure index (ABPI) were also assessed. 123 men returned for
      between visit reproducibility assessments. Results: Good reproducibility was
      demonstrated in all measures (Gwet's agreement=0.8 for plaque, intraclass
      correlation=0.65 for ABPI and coefficient of variation <13% for all other
      measures). Measurements were obtained in >90% of men for all measures except
      cfPWV(S) and ABPI. In 1122 men with both cfPWV(V) and cfPWV(S) data, cfPWV(S) was
      greater than cfPWV(V) (mean difference=0.23,95%CI 0.10 to 0.37 m/s). cfPWV(V) was
      higher at low cfPWV values and cfPWV(S) was higher at high cfPWV values.
      Correlation of V transit time (TT) against S carotid and femoral TT demonstrated
      that the slope of the regression line for femoral TT was steeper than for carotid
      TT, resulting in a proportionally greater subtraction of carotid TT from femoral
      TT at higher PWVs. Conclusions: Reproducible, satisfactory quality non-invasive
      measurements of vascular phenotype were obtainable in a large proportion of
      elderly men. The discrepancy in results between the two PWV measures may partly
      be due to the differential impact of subtracting carotid TT when deriving
      cfPWV(S) across the clinical PWV range.

PMID- 29344366
TI  - Healthcare provider-led interventions to support medication adherence following
      ACS: a meta-analysis.
AB  - : We conducted a systematic review and meta-analysis to determine the
      effectiveness of healthcare provider-led (HCPs) interventions to support
      medication adherence in patients with acute coronary syndrome (ACS). A systematic
      search of Cochrane Library, Medline, EMBASE, PsycINFO, Web of Science, IPA,
      CINAHL, ASSIA, OpenGrey, EthOS, WorldCat and PQDT was undertaken. Interventions
      were deemed eligible if they included adult ACS patients, were HCP-led, measured
      medication adherence and randomised participants to parallel groups. Intervention
      content was coded using the Behaviour Change Technique (BCT) Taxonomy and data
      were pooled for analysis using random-effects models. Our search identified 8870
      records, of which 27 were eligible (23 primary studies). A meta-analysis (n=9735)
      revealed HCP-led interventions increased the odds of medication adherence by 54%
      compared to control interventions (k=23, OR 1.54, 95% CI 1.26 to 1.88, I2=57.5%).
      After removing outliers, there was a 41% increase in the odds of medication
      adherence with moderate heterogeneity (k=21, OR 1.41, 95% CI 1.21 to 1.65,
      I2=35.3%). Interventions that included phone contact yielded (k=12, OR 1.63, 95%
      CI 1.25 to 2.12, I2=32.0%) a larger effect compared to those delivered
      exclusively in person. A total of 32/93 BCTs were identified across interventions
      (mean=4.7, SD=2.2) with 'information about health consequences' (BCT 5.1) (19/23)
      the most common. HCP-led interventions for ACS patients appear to have a small
      positive impact on medication adherence. While we were able to identify BCTs
      among interventions, data were insufficient to determine the impact of particular
      BCTs on study effectiveness. PROSPERO registration number: CRD42016037706.

PMID- 29344367
TI  - Elevated brain natriuretic peptide levels in chronic fatigue syndrome associate
      with cardiac dysfunction: a case control study.
AB  - Objectives: To explore levels of the brain natriuretic peptide (BNP) and how
      these associate with the cardiac abnormalities recently identified in chronic
      fatigue syndrome (CFS). Methods: Cardiac magnetic resonance examinations were
      performed using 3T Philips Intera Achieva scanner (Best, Netherlands) in CFS
      (Fukuda) participants and sedentary controls matched group wise for age and sex.
      BNP was also measured by using an enzyme immunoassay in plasma from 42 patients
      with CFS and 10 controls. Results: BNP levels were significantly higher in the
      CFS cohort compared with the matched controls (P=0.013). When we compared cardiac
      volumes (end-diastolic and end-systolic) between those with high BNP levels (BNP
      >400 pg/mL) and low BNP (<400 pg/mL), there were significantly lower cardiac
      volumes in those with the higher BNP levels in both end-systolic and end
      diastolic volumes (P=0.05). There were no relationships between fatigue severity,
      length of disease and BNP levels (P=0.2) suggesting that our findings are
      unlikely to be related to deconditioning. Conclusion: This study confirms an
      association between reduced cardiac volumes and BNP in CFS. Lack of relationship
      between length of disease suggests that findings are not secondary to
      deconditioning. Further studies are needed to explore the utility of BNP to act
      as a stratification paradigm in CFS that directs targeted treatments. Trail
      registration number: Registered with NIHR Portfolio CLRN ID 97805.

PMID- 29344368
TI  - Inception of the 'endocarditis team' is associated with improved survival in
      patients with infective endocarditis who are managed medically: findings from a
      before-and-after study.
AB  - Objective: Despite improvements in its management, infective endocarditis (IE) is
      associated with poor survival. The aim of this study was to evaluate the impact
      of a multidisciplinary endocarditis team (ET), including a cardiologist,
      microbiologist and a cardiac surgeon, on the outcome of patients with acute IE
      according to medical or surgical treatment strategies. Methods: We conducted an
      observational before-and-after study of 196 consecutive patients with definite
      IE, who were treated at a tertiary reference centre between 2009 and 2015. The
      study was divided into two periods: period 1, before the formation of the ET
      (n=101), and period 2, after the formation of the ET (n=95). The role of the ET
      included regular multidisciplinary team meetings to confirm diagnosis, inform the
      type and duration of antibiotic therapy and recommend early surgery, when
      indicated, according to European guidelines. Results: The patient demographics
      and predisposing conditions for IE were comparable between the two study periods.
      In the time period following the introduction of the ET, there was a reduction in
      both the time to commencement of IE-specific antibiotic therapy (4.0+/-4.0 days
      vs 2.5+/-3.2 days; P=0.004) and the time from suspected IE to surgery (7.8+/-7.3
      days vs 5.3+/-4.2 days; P=0.004). A 12-month Kaplan-Meier survival for patients
      managed medically was 42.9% in the pre-ET period and 66.7% in the post-ET period
      (P=0.03). The involvement of the ET was a significant independent predictor of 1
      year survival in patients managed medically (HR 0.24, 95% CI 0.07 to 0.87;
      P=0.03). Conclusions: A standardised multidisciplinary team approach may lead to
      earlier diagnosis of IE, more appropriate individualised management strategies,
      expedited surgery, where indicated, and improved survival in those patients
      chosen for medical management, supporting the recent change in guidelines to
      recommend the use of a multidisciplinary team in the care of patients with IE.

PMID- 29344369
TI  - Rates and risk of arrhythmias in cancer survivors with chemotherapy-induced
      cardiomyopathy compared with patients with other cardiomyopathies.
AB  - Objectives: There is little information about arrhythmia burden in cancer
      survivors with chemotherapy-induced cardiomyopathy (CIC). We hypothesise that the
      rates and risk of arrhythmias will be similar in CIC when compared with other non
      ischaemic cardiomyopathy (NICMO) aetiologies. Methods: We retrospectively
      identified nine patients with CIC and an implantable defibrillator and 18 age and
      sex-matched control patients (nine patients with NICMO and nine patients with
      ischaemic cardiomyopathy (ICMO)). Rates and odds of arrhythmias were calculated
      by type of cardiomyopathy, adjusting for days since implantable cardioverter
      defibrillator implantation, history of atrial fibrillation and length of follow
      up using logistic regression analysis. Results: Compared with patients with
      NICMO, rates and adjusted odds were similar for patients with CIC for atrial
      arrhythmias (44.4% vs 33.3%; adjusted OR=1.89; 95% CI0.17 to 21.03; P=0.61), non
      sustained ventricular tachycardia (NSVT) (44.4% vs 33.3%; OR=2.10; 95% CI 0.21 to
      20.56; P=0.53), and the combined outcome of NSVT, sustained ventricular
      tachycardia and/or ventricular fibrillation (44.4% vs 44.4%; OR=2.70; 95% CI 0.25
      to 29.48; P=0.42). Conversely, compared with patients with NICMO, patients with
      ICMO demonstrated higher rates and adjusted odds of the combined outcome (88.9%
      vs 44.4%; OR=28.60; 95% CI 1.26 to 648.2; P=0.04) and NSVT (77.8% vs 33.3%;
      OR=8.95; 95% CI 0.90 to 88.94; P=0.06). Conclusions: While tentative based on
      sample size, rates of arrhythmias in patients with CIC appear to be similar to
      those experienced by patients with other forms of NICMO.

PMID- 29344370
TI  - Prevalence and prognostic value of echocardiographic screening for rheumatic
      heart disease.
AB  - Objective: Rheumatic heart disease (RHD) remains a major health problem in many
      low-income and middle-income countries. The use of echocardiographic imaging
      suggests that subclinical disease is far more widespread than previously
      appreciated, but little is known as to how these mild forms of RHD progress. We
      have determined the prevalence of subclinical RHD in a large group of
      schoolchildren in Aswan, Egypt and have evaluated its subsequent progression.
      Methods: Echocardiographic screening was performed on 3062 randomly selected
      schoolchildren, aged 5-15 years, in Aswan, Egypt. Follow-up of children with a
      definite or borderline diagnosis of RHD was carried out 48-60 months later to
      determine how the valvular abnormalities altered and to evaluate the factors
      influencing progression. Results: Sixty children were initially diagnosed with
      definite RHD (19.6 per 1000 children) and 35 with borderline disease (11.4 per
      1000); most had mitral valve disease. Of the 72 children followed up progression
      was documented in 14 children (19.4%) and regression in 30 (41.7%) children. Boys
      had lower rates of progression while older children had lower rates of
      regression. Functional defects of the valve even in the presence of structural
      features were associated with lower rates of progression and higher rates of
      regression than structural changes. Conclusions: RHD has a high prevalence in
      Egypt. Although a high proportion of the abnormalities originally detected
      persisted at follow-up, both progression and regression of valve lesions were
      demonstrated.

PMID- 29344371
TI  - Accrual monitoring in cardiovascular trials.
AB  - Objective: To provide brief guidance on how to design accrual monitoring
      activities in a clinical trial protocol. Setting: Two completed clinical trials
      that did not achieve the planned sample size, the Cost of Strategies After
      Myocardial Infarction (COSTAMI) trial and the Biventricular Pacing After Cardiac
      Surgery (BiPACS) trial. Design: A Bayesian monitoring tool, the constant accrual
      model, is applied retrospectively to accrual data from each case study to
      illustrate how the tool could be used to identify problems with accrual early in
      the trial period and to frame the conditions in which the approach can be used in
      practice. Results: After 312 days and 155 patients enrolled in the COSTAMI trial,
      accrual could be classified as 'off target' on the basis of statistical criteria
      outlined in the protocol. As for the BiPACS trial, after 2 years, it was already
      evident that the accrual was 'considerably off target'. Conclusions: Prompt
      awareness of a high risk of accrual failure could trigger different interventions
      to overcome protocol-related, patient-related or investigator-related barriers to
      recruitment or ultimately contribute to an early stopping decision due to
      recruitment futility.Accrual prediction models should be included as standard
      tools for routine monitoring activities in cardiovascular research. Among them,
      methods relying on the Bayesian approach are particularly attractive, as they can
      naturally update past evidence when actual accrual data becomes available.

PMID- 29344372
TI  - Association of high-density lipoprotein cholesterol with non-fatal cardiac and
      non-cardiac events: a CANHEART substudy.
AB  - Background: Emerging evidence has questioned the role of high-density lipoprotein
      cholesterol (HDL-C) as an independent and modifiable risk factor for
      cardiovascular disease. We sought to understand the relationship between HDL-C
      levels and subsequent non-fatal clinical events. Methods: Individuals without
      prior cardiovascular disease or cancer were identified. Outcomes of interest were
      classified as non-fatal cardiovascular, cancer and infectious. Sex-stratified,
      multivariable, cause-specific Cox proportional hazards models were created. The
      reference level HDL-C for both women and men was 51-60 mg/dL. Results: Our cohort
      consisted of 631 762 individuals. For cardiovascular events, there was a
      consistent inverse relationship, with higher adjusted HRs for the lower HDL-C
      strata in both men and women. This relationship was also seen in the composite of
      non-cardiovascular outcomes. In women, the HR in the <30 mg/dL HDL-C category was
      2.10 (95% CI 1.66 to 2.57) and 1.86 (95% CI 1.27 to 2.72) for cardiovascular and
      non-cardiovascular outcomes, respectively; in contrast, in the >90 mg/dL group,
      it was 0.87 (95% CI 0.74 to 1.02) and 0.81 (95% CI 0.63 to 1.06). For men, HRs
      were 2.02 (95% CI 1.79 to 2.28) and 1.84 (95% CI 1.47 to 2.31) in the <30 mg/dL
      HDL-C category for cardiovascular and non-cardiovascular outcomes, respectively,
      compared with 0.73 (95% CI 0.53 to 1.00) and 1.07 (95% CI 0.67 to 1.70) in the
      >90 mg/dL group. Conclusions: We found an inverse relationship between HDL-C and
      a wide spectrum of non-fatal outcomes, suggesting that HDL-C is a heavily
      confounded factor that may be a marker of poor overall health, rather than an
      independent and modifiable risk factor.

PMID- 29344373
TI  - Multianalysis with optical coherence tomography and vasomotion in everolimus
      eluting stents and everolimus-eluting biovascular scaffolds: the MOVES trial.
AB  - Aims: To compare endothelium-dependent vasomotor function and vascular healing 15
      months after implantation of two new-generation drug-eluting stents and
      biovascular scaffolds (BVS). Methods and results: A total of 28 patients
      previously treated with a SYNERGY stent (bioabsorbable polymer everolimus-eluting
      stents (BP-EES)), a PROMUS stent (persistent polymer everolimus-eluting stents
      (PP-EES)) or an ABSORB (BVS) underwent control coronary angiography, 15 months
      after implantation, coupled with optical coherence tomography imaging and supine
      bicycle exercise. Intracoronary nitroglycerin was administered after exercise
      testing. Coronary vasomotor response was assessed using quantitative coronary
      angiography at rest, during supine bicycle exercise and after nitroglycerin. The
      primary end point was the percent change in mean lumen diameter compared with
      baseline. Secondary end points were strut coverage and apposition.There were no
      significant differences in vasomotor response between the three treatment groups.
      Patients with PP-EES showed significant vasoconstriction of the proximal
      peristent segment at maximum exercise (P=0.02). BP-EES (2.7%, 95% CI 0 to 5.5)
      and BVS (3.2%, 95% CI 0 to 6.7) showed less uncovered struts than PP-EES (12.1%,
      95% CI 2.9 to 21.3, P=0.02 and 0.09, respectively). Complete strut apposition was
      more frequently seen with BP-EES (99.6%, 95% CI 99.2 to 100) than with BVS
      (98.9%, 95% CI 98.2 to 99.6, P=0.04) or PP-EES (95.0%, 95% CI 91.6 to 98.5,
      P=0.001). Conclusion: BVS and thin strut BP-EES have a reassuring vasomotion
      profile, suggesting minimal endothelial dysfunction 15 months after implantation.

PMID- 29344374
TI  - Cardioprotection by an anti-MASP-2 antibody in a murine model of myocardial
      infarction.
AB  - Background: Myocardial ischaemia-reperfusion injury is a major cause of mortality
      and morbidity in the developed world. Many approaches have been investigated to
      counteract the pathological consequences associated with acute myocardial
      infarction (AMI) and cardiac remodelling. It is accepted that inflammation, and
      therefore activation of the complement pathway, is a crucial step in the
      pathogenesis of this injury, and many attempts have been made to ameliorate the
      infarction and consequent dysfunction using anticomplement therapy, with mixed
      success. Recently, the lectin complement activation pathway involving the mannose
      binding lectin-associated serine protease 2 (MASP-2) has been shown to be an
      important mediator of the inflammatory response in ischaemia/reperfusion injury
      in the heart. In this study, therefore, we aimed to investigate the feasibility
      of using monoclonal antibodies raised against MASP-2 in a murine model of AMI.
      Methods: Mice were injected with anti-MASP-2 antibody or control 18 hours prior
      to experimental infarction by ligation of the left anterior descending coronary
      artery for 30 min followed by 120 min reperfusion. The developed infarct was
      measured, and blood was collected for analysis of lectin pathway functional
      activity. Results and conclusions: We found that mice treated with anti-MASP-2
      antibody had smaller infarcts than those treated with control antibody. We
      believe this may represent a valuable step forward in the protection of the
      myocardium against ischaemia-reperfusion injury.

PMID- 29344375
TI  - Elevated serum levels of cardiovascular biomarkers are associated with
      progression of renal cancer.
AB  - Objective: Renal cell carcinoma (RCC) is a hypervascular tumour due to high
      constitutive production of vascular endothelial growth factor (VEGF), which is
      activated by hypoxia-inducible factor (HIF). Elevated levels of cardiovascular
      peptides, including brain natriuretic peptide (BNP), have been reported in
      patients with cancer, regardless of whether they have overt cardiovascular
      disease. Furthermore, it has been demonstrated that hypoxia stimulates BNP
      production by an HIF-dependent manner. However, the clinical implications of such
      cardiovascular peptides in patients with RCC have not been assessed. Methods: In
      patients with clear cell RCC who underwent nephrectomy, we investigated the
      relationship between the serum level of BNP or N-terminal pro-BNP (NT-proBNP) and
      various clinicopathological characteristics, including serum VEGF and expression
      of BNP and HIF-2 alpha in the primary tumour. Results: Elevated preoperative
      serum levels of BNP, NT-proBNP and VEGF, as well as increased tumour expression
      of HIF-2 alpha, were associated with a worse performance status, local invasion,
      distant metastasis and shorter overall survival. HIF-2 alpha expression showed a
      positive correlation with the preoperative serum VEGF level, while there was no
      relation between the serum levels of BNP/NT-proBNP and VEGF or tumour expression
      of HIF-2 alpha. BNP expression was very low in both tumour tissues and normal
      kidney tissues. Serum levels of BNP, NT-proBNP and VEGF all decreased
      significantly after nephrectomy. Conclusions: Our findings suggested that the
      preoperative serum levels of BNP and NT-proBNP are markers of tumour progression,
      as well as indicators of subclinical functional and structural myocardial damage
      in patients with advanced RCC.

PMID- 29344376
TI  - Effectiveness of pharmacist's intervention in the management of cardiovascular
      diseases.
AB  - The pharmacist may play a relevant role in primary and secondary prevention of
      cardiovascular diseases, mainly through patient education and counselling, drug
      safety management, medication review, monitoring and reconciliation, detection
      and control of specific cardiovascular risk factors (eg, blood pressure, blood
      glucose, serum lipids) and clinical outcomes. Systematic reviews of randomised
      controlled and observational studies have documented an improved control of
      hypertension, dyslipidaemia or diabetes, smoking cessation and reduced
      hospitalisation in patients with heart failure, following a pharmacist's
      intervention. Limited proof for effectiveness is available for humanistic
      (patient satisfaction, adherence and knowledge) and economic outcomes. A
      multidisciplinary approach, including medical input plus a pharmacist, specialist
      nurse or both, and a greater involvement of community rather than hospital
      pharmacists, seems to represent the most efficient and modern healthcare delivery
      model. However, further well-designed research is demanded in order to
      quantitatively and qualitatively evaluate the impact of pharmacist's
      interventions on cardiovascular disease and to identify specific areas of impact
      of collaborative practice. Such research should particularly focus on the
      demonstration of a sensitivity to community pharmacist's intervention. Since
      pharmacy services are easily accessible and widely distributed in the community
      setting, a maximum benefit should be expected from interventions provided in this
      context.

PMID- 29344377
TI  - Major adverse cardiac and cerebrovascular event and patients' quality of life
      after endoscopic vein harvesting as compared with open vein harvest (MAQEH): a
      pilot study.
AB  - Background: This is a prospective, comparative, pilot and follow-up (2-year
      postoperatively) study in patients undergoing coronary artery bypass graft
      surgery where the long saphenous vein was harvested either by the endoscopic vein
      harvest (EVH) technique or open vein harvest (OVH) technique. Quality of life
      (QOL) and major adverse cardiac and cerebrovascular events (MACCE) were assessed.
      Methods: Alive patients who were initially part of a pilot study when EVH was
      introduced in our institution were included (n=48 EVH, n=49 OVH). Patients were
      sent a QOL questionnaire (SF12v2; 12-item medical outcomes study short form
      health survey version 2.0), and their cardiologist and general practitioner were
      contacted to assess MACCE. Results: Median follow-up was 32 and 33 months,
      respectively. Three patients died (2 EVH, 1 OVH). Of the remaining 97 patients
      who were sent a questionnaire, 76% patients returned the form. More patients from
      the EVH group returned the QOL questionnaire (82% vs 71%). Time taken to return
      to normal daily activities was much shorter in EVH (median 6 (2-30) weeks)
      compared with OVH (median 9 (2-50) weeks) (P<0.05). QOL questionnaire revealed
      significant difference in physical score at follow-up: 45.3 (10.2) for EVH group
      and 40.7 (11.0) for OVH group (P<0.05). There was no difference in mental scores
      (46.9 (10.5) vs 49.2 (9.1), P=0.4). There were no significant differences in
      MACCEs including death between the two groups (12.2% vs 13.9%, P=0.5).
      Conclusion: EVH patients returned to normal daily activities faster than OVH
      patients and experienced better physical QOL even after 2 years postoperatively
      with no increase in MACCE during follow-up.

PMID- 29344378
TI  - Clinical outcomes and costs of cardiac revascularisation in England and New York
      state.
AB  - Objectives: Healthcare expenditure per-capita in the USA is higher than in
      England. We hypothesised that clinical outcomes after cardiac revascularisation
      are better in the USA. We compared costs and outcomes of patients undergoing
      coronary artery bypass grafting (CABG) and percutaneous coronary intervention
      (PCI) in England and New York State (NYS). Methods: Costs and total mortality
      were assessed using the Hospital Episode Statistics for England and the Statewide
      Planning and Research Cooperative System for NYS. Outcomes after a first CABG or
      PCI were assessed in patients undergoing a first CABG (n=142 969) or PCI (n=431
      416). Results: After CABG, crude total mortality in England was 0.72% lower at 30
      days and 3.68% lower at 1 year (both P<0.001). After PCI, crude total mortality
      was 0.35% lower at 30 days and 3.55% lower at 1 year (both P<0.001). No
      differences emerged in total mortality at 30 days after either CABG (England: HR
      1.02,95% CI 0.94 to 1.10) or PCI (HR 1.04, 95% CI 0.99 to 1.09) after covariate
      adjustment. At 1 year, adjusted total mortality was lower in England after both
      CABG (HR 0.74, 95% CI 0.71 to 0.78) and PCI (HR 0.66, 95% CI 0.65 to 0.68). After
      adjustment for cost-to-charge ratios and purchasing power parities, costs in NYS
      amounted to uplifts of 3.8-fold for CABG and 3.6-fold for PCI. Conclusions: Total
      mortality after CABG and PCI was similar at 30 days and lower in England at 1
      year. Costs were approximately fourfold higher in NYS.

PMID- 29344379
TI  - Changes in contractile protein expression are linked to ventricular stiffness in
      infants with pulmonary hypertension or right ventricular hypertrophy due to
      congenital heart disease.
AB  - Background: The right ventricle (RV) is not designed to sustain high pressure
      leading to failure. There are no current medications to help RV contraction, so
      further information is required on adaption of the RV to such hypertension.
      Methods: The Right Ventricle in Children (RVENCH) study assessed infants with
      congenital heart disease undergoing cardiac surgery with hypertensive RV.
      Clinical and echocardiographic data were recorded, and samples of RV were taken
      from matched infants, analysed for proteomics and compared between pathologies
      and with clinical and echocardiographic outcome data. Results: Those with
      tetralogy of Fallot (TOF) were significantly more cyanosed than those with
      ventricular septal defect (median oxygen saturation 83% vs 98%, P=0.0038), had
      significantly stiffer RV (tricuspid E wave/A wave ratio 1.95 vs 0.84, P=0.009)
      and had most had restrictive physiology. Gene ontology in TOF, with enrichment
      analysis, demonstrated significant increase in proteins of contractile mechanisms
      and those of calmodulin, actin binding and others associated with contractility
      than inventricular septal defect. Structural proteins were also found to be
      higher in association with sarcomeric function: Z-disc, M-Band and thin-filament
      proteins. Remaining proteins associated with actin binding, calcium signalling
      and myocyte cytoskeletal development. Phosphopeptide enrichment led to higher
      levels of calcium signalling proteins in TOF. Conclusion: This is the first
      demonstration that those with an RV, which is stiff and hypertensive in TOF, have
      a range of altered proteins, often in calcium signalling pathways. Information
      about these alterations might guide treatment options both in terms of
      individualised therapy or inotropic support for the Right ventricle when
      hypertensive due to pulmoanry hypertension or congenital heart disease.

PMID- 29344380
TI  - Sex-stratified analysis of national trends and outcomes in isolated tricuspid
      valve surgery.
AB  - Objective: Female sex is a known risk factor for cardiac surgery, and tricuspid
      valve (TV) disease is more common in women. There are few data on sex-stratified
      surgical outcomes for isolated TV surgery. An administrative database was used to
      compare acute in-hospital outcomes between men and women undergoing isolated TV
      surgery. Methods: Patients aged >18 who underwent TV repair or replacement from
      2004 to 2013 were identified using the National Inpatient Sample. Patients were
      excluded if they had congenital heart disease, endocarditis, or were undergoing
      concomitant cardiac surgeries except coronary bypass. Results were weighted to
      represent national averages. Sex-stratified analysis was performed using
      propensity score matching to compare in-hospital mortality, postoperative
      complications and hospital costs. Results: Over 10 years, women represented 58%
      of the 5005 TV surgeries performed. With propensity matching, hospital mortality
      (7.9% vs 7.7%; P=0.99) and median length of stay (11 vs 11 days; P=0.99) were
      similar between men and women. However, median hospital charges were higher for
      men ($166 000 vs $155 000; P=0.04). Conclusion: Isolated TV surgery is rare, but
      women more commonly undergo the procedure. In-hospital mortality was similar
      between men and women after propensity matching, but remains markedly high for
      both men and women in comparison to that reported for left-sided isolated valve
      surgery.

PMID- 29344381
TI  - Impact of nutritional indices on mortality in patients with heart failure.
AB  - Background: Malnutrition is a common condition that is associated with adverse
      prognosis in patients with heart failure (HF). The Prognostic Nutritional Index
      (PNI), Geriatric Nutritional Risk Index (GNRI) and controlling nutritional status
      (CONUT) have all been used as objective indices for evaluating nutritional
      status. We aimed to clarify the relationship between these nutritional indices
      and the parameters of inflammatory markers, cardiac function and exercise
      capacity, as well as to compare the ability of these indexes for predicting
      mortality. Methods: We evaluated PNI, GNRI and CONUT in consecutive 1307 patients
      with HF. Results: First, there were significant correlations between nutritional
      indices and the following: C reactive protein; tumour necrosis factor-alpha;
      adiponectin; B-type natriuretic peptide; troponin I; inferior vena cava diameter
      and peak VO2 (P<0.05, respectively). Second, in the Kaplan-Meier analysis (follow
      up 1146 days), all-cause mortality progressively increased from normal to mild,
      moderate and severe disturbance groups in the indices (log-rank, P<0.01,
      respectively). In the Cox proportional hazard analysis, each index was an
      independent predictor of all-cause mortality in patients with HF (P<0.001,
      respectively). Third, receiver operating curve demonstrated that the areas under
      the curve of PNI and GNRI were larger than that of CONUT score (P<0.05,
      respectively). Conclusion: Patients with HF being malnourished had higher
      mortality accompanied by higher levels of C reactive protein, tumour necrosis
      factor-alpha, adiponectin, B-type natriuretic peptide, troponin I, right-sided
      volume overload and impaired exercise capacity, rather than left ventricular
      systolic function. Additionally, PNI and GNRI were superior to CONUT score in
      predicting mortality in patients with HF.

PMID- 29344382
TI  - Advanced therapies for the management of adults with pulmonary arterial
      hypertension due to congenital heart disease: a systematic review.
AB  - Pulmonary arterial hypertension (PAH) secondary to congenital heart disease (CHD)
      is the third most common cause of PAH, and it is becoming increasingly common as
      improvements in the management of CHD have led to increased life expectancy for
      these patients. The medical management of PAH due to CHD (PAH-CHD) is largely the
      same as what has been used for the treatment of idiopathic PAH, though the body
      of literature supporting this management decision is very small. There are
      currently few studies available which specifically focus on the treatment of PAH
      CHD. The purpose of this literature review is to compare the results of those
      studies that assessed the response to medical therapy among adults with PAH-CHD;
      studies were excluded if they focused on paediatric patients, did not include an
      assessment of 6 min walking distance or specifically assessed combination
      therapies. This review found that riociguat, bosentan, epoprostenol and
      sildenafil were all capable of improving functional capacity and haemodynamic
      parameters in patients with PAH-CHD, but whether this corresponds to an increase
      in mortality remains to be seen. Limitations of this review include the small
      sample size and variable duration of the included studies, which makes drawing
      direct comparisons between studies and the study drugs difficult. The lack of
      large, randomised double-blind clinical trials comparing different drugs head to
      head highlights an area that is ripe for ongoing medical research, the results of
      which may help shape future treatment algorithms tailored specifically for adults
      with PAH-CHD.

PMID- 29344383
TI  - Prognosis of patients with secondary mitral regurgitation and reduced ejection
      fraction.
AB  - Objective: The impact of the severity of secondary mitral regurgitation (MR) on
      the risk of death and heart failure (HF) hospitalisations in patients with
      reduced left ventricular (LV) systolic function is poorly defined. The study
      sought to identify the incremental risk of secondary MR in patients with reduced
      LV systolic function. Methods: We studied 615 consecutive patients with LV
      ejection fraction <=35% by transthoracic echocardiography at a single medical
      centre. Patients were divided into three groups of no MR, mild, or moderate to
      severe MR. The median follow-up was 2.9 years. The primary endpoint was a
      composite of death or HF hospitalisations. Results: Compared with patients with
      no MR, the risk of death or HF hospitalisations was higher for mild MR (HR 1.7,
      P=0.003) and moderate to severe MR (HR 2.7, P<0.001). The risk was also higher
      for the component endpoints of HF hospitalisations (mild MR: HR 2.3, P=0.001;
      moderate to severe MR: HR 3.5, P<0.001) and death (mild MR: HR 1.6, P=0.033;
      moderate to severe MR: HR 2.6, P<0.001). After adjustment for other covariates,
      MR was no longer significantly associated with death or HF hospitalisations, or
      death alone, but remained significantly associated with HF hospitalisations (mild
      MR: HR 1.7, P=0.028; moderate to severe MR: HR 2.2, P=0.002). Conclusions: In
      patients with reduced LV systolic function, secondary MR is associated with an
      increased risk of HF hospitalisations but not death.

PMID- 29344384
TI  - Blood pressure target achievement and antihypertensive medication use in women
      and men after first-ever myocardial infarction: the Tromso Study 1994-2016.
AB  - Background: Recurrent cardiovascular events after myocardial infarction (MI) are
      frequent, and gender differences in blood pressure treatment have been reported.
      Despite increased focus on secondary prevention, recent reports indicate that
      treatment targets are not achieved. There is a need for gender-specific analyses
      of post-MI blood pressure treatment target achievement and antihypertensive
      medication adherence. Design: We investigated the change in systolic and
      diastolic blood pressure and antihypertensive drug use after first-ever MI over
      two time periods in a Norwegian population-based study. Methods: We followed 10
      089 participants (55% women) attending the Tromso Study in 1994-1995 (MI-cohort
      I) and 8412 participants (55% women) attending the Tromso Study 2007-2008 (MI
      cohort II) for first-ever MI up to their participation in 2007-2008 and 2015
      2016, respectively. We used linear regression models to investigate sex and age
      differences in change in blood pressure. Results: A total of 396 participants in
      MI-cohort I and 131 participants in MI-cohort II had a first-ever MI in the
      observation periods. In MI-cohort I, 35% of the women and 52% of the men achieved
      the treatment targets of blood pressure <140/90 mm Hg (130/80 mm Hg if diabetic),
      while the proportions for MI-cohort II were 50% and 54% for women and men,
      respectively. Antihypertensive use was reported in 88% of women and 87% of men in
      MI-cohort I, and 76% of women and 81% of men in MI-cohort II. Conclusions: We
      found an overall low achievement of the treatment target. The findings call for
      better strategies for secondary prevention for both women and men.

PMID- 29344385
TI  - Improving attendance to genetic counselling services for gynaecological oncology
      patients.
AB  - Background: Gynaecological cancers may be the sentinel malignancy in women who
      carry a mutation in BRCA1 or 2, a mis-match repair gene causing Lynch Syndrome or
      other genes. Despite published guidelines for referral to a genetics service, a
      substantial number of women do not attend for the recommended genetic assessment.
      The study aims to determine the outcomes of systematic follow-up of patients
      diagnosed with ovarian or endometrial cancer from Gynaecologic-oncology
      multidisciplinary meetings who were deemed appropriate for genetics assessment.
      Methods: Women newly diagnosed with gynaecological cancer at the Royal Hospital
      for Women between 2010 and 2014 (cohort1) and 2015-2016 (cohort 2) who were
      identified as suitable for genetics assessment were checked against the New South
      Wales/Australian Capital Territory genetic database. The doctors of non-attenders
      were contacted regarding suitability for re-referral, and patients who were still
      suitable for genetics assessment were contacted by mail. Attendance was again
      checked against the genetics database. Results: Among 462 patients in cohort 1,
      flagged for genetic assessment, 167 had not consulted a genetic service at
      initial audit conducted in 2014. 86 (18.6%) women whose referral was pending
      clarification of family history and/or immunohistochemistry did not require
      further genetic assessment. Letters were sent to 40 women. 7 women (1.5%)
      attended hereditary cancer clinic in the following 6 months.The audit conducted
      in 2016 identified 148 patients (cohort 2) appropriate for genetic assessment at
      diagnosis. 66 (44.6%) had been seen by a genetics service, 51 (34.5%) whose
      referral was pending additional information did not require further genetic
      assessment. Letters were sent to 15 women, of whom 9 (6.1%) attended genetics
      within 6 months. Conclusions: To improve the effectiveness of guidelines for the
      genetic referral of women newly diagnosed with ovarian cancer, clinicians need to
      obtain a thorough family history at diagnosis; arrange for reflex MMR IHC
      according to guidelines; offer BRCA or panel testing to all women with non
      mucinous ovarian cancer prior to discharge and systematically follow up all women
      referred to genetics at the post-op visit.

PMID- 29344386
TI  - Current and future therapies for SLE: obstacles and recommendations for the
      development of novel treatments.
AB  - SLE is a serious, debilitating autoimmune disease that affects various organs and
      body systems. Of all the heterogeneous autoimmune diseases, SLE is perhaps the
      most heterogeneous. Patients with SLE, who are primarily female, have diverse
      disease manifestations and severity. SLE is characterised by substantial
      concentrations of autoantibodies against nuclear antigens, which are thought to
      be caused by immune cell dysregulation. Until recently, several immunosuppressant
      agents were used to treat this disease. Efforts to develop drugs against targets
      potentially involved in disease mechanisms have resulted in the identification
      and use of BAFF (B-cell activating factor)/APRIL (a proliferation-inducing
      ligand) inhibitors to treat SLE. Drugs in late-stage development that focus on
      pathways that are dysregulated in SLE include those that target the interferon
      pathway, T-cell signalling and B-cell signalling. New therapeutic agents are
      still necessary because of the unmet medical needs associated with this disease,
      including insufficient disease control, poor health-related quality of life,
      comorbidities, toxicity of the majority of therapies and diminished survival.
      Despite the substantial long-term investment of research, clinical activity and
      resources for identifying new treatments for this disease, only one new therapy,
      the biological belimumab, has been approved in the past 50 years. Efforts to
      develop drugs to address these needs are challenged by problems associated with
      disease heterogeneity, variable disease mechanisms and trial design. This review
      provides an overview of current and future treatments, discusses challenges in
      the SLE drug development process and offers recommendations for overcoming these
      challenges.

PMID- 29344387
TI  - Repository corticotropin injection in patients with persistently active SLE
      requiring corticosteroids: post hoc analysis of results from a two-part, 52-week
      pilot study.
AB  - Objective: Post hoc analyses evaluated the effectiveness and safety of repository
      corticotropin injection (RCI) in patients with persistently active SLE over 52
      weeks. Methods: Patients were initially randomised to 40 U daily or 80 U every
      other day RCI (n=26) or placebo (n=12) for the 8-week double-blind period.
      Completers entered the open-label extension (OLE; n=33) receiving 16, 40 or 80 U
      RCI 1-3 times/week and were followed through week 52. Outcomes included
      proportion of responders based on a novel index (resolution of joint or skin
      activity using hybrid Systemic Lupus Erythematosus Disease Activity Index
      (hSLEDAI) without any worsening British Isles Lupus Assessment Group (BILAG)
      scores in other organ systems) or revised novel index (using SLE Responder Index
      (SRI) definition of BILAG worsening (1A or 2B)), proportion of responders by SRI
      and changes in total hSLEDAI and BILAG scores. Adverse events and laboratory
      values were assessed. Results: At week 52, 12.0% (3/25) RCI/RCI patients and
      36.4% (4/11) placebo/RCI patients were responders using the novel index. The
      revised novel responder index demonstrated response rates of 48.0% (12/25) and
      54.5% (6/11) in the RCI/RCI and placebo/RCI groups, respectively. Proportions of
      SRI responders were 40.0% (10/25) and 54.5% (6/11). In the RCI/RCI group, total
      hSLEDAI and BILAG scores declined from 10.0 and 15.7 at week 0 to 3.5 and 4.6 at
      week 52, respectively. Reductions in the placebo/RCI group on switching were
      observed (mean hSLEDAI: 9.1-3.3; BILAG: 13.5-2.6). Other disease activity
      endpoints also improved in both groups. No new safety signals were observed
      during the OLE. Conclusions: RCI demonstrated durable effectiveness in patients
      with persistently active SLE despite moderate-dose corticosteroid therapy.
      Switching from placebo resulted in reduced disease activity during the OLE. These
      data provide the foundation for evaluation of RCI in a robustly powered study.

PMID- 29344388
TI  - Gender-based violence and the role of healthcare professionals.

PMID- 29344389
TI  - Family members' satisfaction with care and decision-making in intensive care
      units and post-stay follow-up needs-a cross-sectional survey study.
AB  - Aim: The aim of this study was to explore family members' satisfaction with care
      and decision-making during the intensive care units stay and their follow-up
      needs after the patient's discharge or death. Design: A cross-sectional survey
      study was conducted. Methods: Family members of patients recently treated in an
      ICU were participating. The questionnaire contented of background variables, the
      instrument Family Satisfaction in ICU (FS-ICU 24) and questions about follow-up
      needs. Descriptive and non-parametric statistics and a multiple linear regression
      were used in the analysis. Results: A total of 123 (47%) relatives returned the
      questionnaire. Satisfaction with care was higher scored than satisfaction with
      decision-making. Follow- up needs after the ICU stay was reported by 19 (17%) of
      the participants. Gender and length of the ICU stay were shown as factors
      identified to predict follow-up needs.

PMID- 29344390
TI  - Job-related stress in psychiatric assistant nurses.
AB  - Aim: We aimed to clarify how stress among psychiatric assistant nurses (PANs)
      differed from Registered Nurses (PRNs). Design: Cross-sectional survey study was
      conducted with PRNs and PANs working in six psychiatric hospitals in Japan.
      Methods: The Psychiatric Nurse Job Stressor Scale (PNJSS) and the job stressor
      and stress reaction subscales of the Brief Job Stress Questionnaire measured
      stress in 68 PANs and 140 PRNs. The results were statistically analysed. Results:
      Psychiatric assistant nurses had significantly higher scores than PRNs on the job
      stressor subscales in psychiatric nursing ability, interpersonal relations and in
      the stress reaction subscales of irritability and somatic symptoms. "Psychiatric
      nursing ability," "Communication" and "Use of techniques" were associated with
      almost all stress reactions in PANs than in PRNs.

PMID- 29344391
TI  - Pilot study: Assessing the effect of continual position monitoring technology on
      compliance with patient turning protocols.
AB  - Aim: The study aim was to evaluate if continual patient position monitoring,
      taking into account self-turns and clinician-assisted turns, would increase the
      percentage of time a patient's position changed at least every 2 hr. Background:
      While patient turning has clinical benefits, current models to help staff
      remember to turn patients, such as "turn clocks" and timers, have not resulted in
      high compliance with turning protocols. In addition, reminders are based on
      arbitrary 2-hr windows (such as turning on "even" hours) rather than on
      individual patient activity, including self-turns. Design: This is a first
      inpatient, non-randomized, pre-/postintervention study. Methods: Data collection
      occurred from May 2013-February 2014 on a 39-bed medical unit in a community
      hospital. Baseline patient turning data were recorded by a sensor; however, the
      patient data were not displayed at the nurses' station to establish compliance
      with the hospital's turning protocol. Postintervention, patient position
      information was wirelessly displayed on nurses' station computer monitors in real
      time. A Student t test was used to compare baseline to postintervention "mean
      time in compliance." Results: Data from 138 patients (N = 7,854 hr of monitoring)
      were collected. The baseline phase yielded 4,322 hr of position monitoring data
      and the postintervention phase yielded 3,532 hr of data. Statistically
      significant improvement was demonstrated in the percentage of time a patient's
      position changed at least every 2 hr from baseline to postintervention.

PMID- 29344392
TI  - Evaluating the parent-adolescent communication toolkit: Usability and preliminary
      content effectiveness of an online intervention.
AB  - Aim: This study aimed to assess the Parent-Adolescent Communication Toolkit, an
      online intervention designed to help improve parent communication with their
      adolescents. Participant preferences for two module delivery systems (sequential
      and unrestricted module access) were identified. Design: Usability assessment of
      the PACT intervention was completed using pre-test and posttest comparisons.
      Usability data, including participant completion and satisfaction ratings were
      examined. Methods: Parents (N = 18) of adolescents were randomized to a
      sequential or unrestricted chapter access group. Parent participants completed
      pre-test measures, the PACT intervention and posttest measures. Participants
      provided feedback for the intervention to improve modules and provided usability
      ratings. Adolescent pre- and posttest ratings were evaluated. Results: Usability
      ratings were high and parent feedback was positive. The sequential module access
      groups rated the intervention content higher and completed more content than the
      unrestricted chapter access group, indicating support for the sequential access
      design. Parent mean posttest communication scores were significantly higher (p <
      .05) than pre-test scores. No significant differences were detected for
      adolescent participants. Findings suggest that the Parent-Adolescent
      Communication Toolkit has potential to improve parent-adolescent communication
      but further effectiveness assessment is required.

PMID- 29344393
TI  - Effect of standardized nursing language continuing education programme on nurses'
      documentation of care at University College Hospital, Ibadan.
AB  - Aim: The study assessed the documentation of nursing care before, during and
      after the Standardized Nursing Language Continuing Education Programme (SNLCEP).
      It evaluates the differences in documentation of nursing care in different
      nursing specialty areas and assessed the influence of work experience on the
      quality of documentation of nursing care with a view to provide information on
      documentation of nursing care. The instrument used was an adapted scoring guide
      for nursing diagnosis, nursing intervention and nursing outcome (Q-DIO). Design:
      Retrospective record reviews design was used. Methods: A total of 270 nursing
      process booklets formed the sample size. From each ward, 90 booklets were
      selected in this order: 30 booklets before the SNLCEP, 30 booklets during SNLCEP
      and 30 booklets after SNLCEP. Results: Overall, the study concluded that the
      SNLCEP had a significant effect on the quality of documentation of nursing care
      using Standardized Nursing Languages.

PMID- 29344394
TI  - Patient participation, a prerequisite for care: A grounded theory study of
      healthcare professionals' perceptions of what participation means in a paediatric
      care context.
AB  - Aims: To explore healthcare professionals' perceptions of what patient
      participation means in a paediatric care context . Design: A qualitative
      explorative design with grounded theory. Methods: Fifteen healthcare
      professionals who worked in paediatric care settings were either interviewed or
      asked open-ended questions in a survey, during December 2015-May 2016. Grounded
      theory was used as a method. Results: The study results provide a theoretical
      conceptualization of what patient participation meant for healthcare
      professionals in paediatric care and how participation was enabled. The core
      category "participation a prerequisite for care" emerged as the main finding
      explaining the concept as ethical, practical and integrated in the care givers
      way of working. However, the concept was implicit in the organization. Four
      additional categories illustrated the healthcare professionals' different
      strategies used to enhance patient participation; "meeting each child where the
      child is," "building a relationship with the child," "showing respect for each
      individual child" and "making the most of the moment."

PMID- 29344395
TI  - Nurse anaesthetist students' experiences of patient dignity in perioperative
      practice-a hermeneutic study.
AB  - Aim: The aim of the study was to describe how nurse anaesthetist students
      experienced patient dignity in perioperative practice. Design: A hermeneutical
      design and the critical incident technique were used to obtain experiences from
      practice. Method: In the Autumn of 2015, after participating in a mandatory
      lecture on ethics, 23 nurse anaesthetist students reported their experiences and
      interpretation concerning violation and preservation of patients' dignity in the
      operating theatre. The text, which was a compilation of descriptions of 35
      incidents, was analysed by using hermeneutical text interpretation. Findings: The
      text revealed three main themes preserving patients' dignity: allocating time to
      the patient, inviting the patient to participate and shielding the patient's
      body. Furthermore, three main themes of dignity violation were identified:
      alienation, backbiting and violation of intimate sphere. Conclusion: Discussion
      and reflection based on the personal experience of the students during their
      practice are ways to strengthen ethical awareness and promote an ethical and
      dignified caring culture.

PMID- 29344396
TI  - Adversity of prolonged extreme cold exposure among adult clients diagnosed with
      coronary artery diseases: a primer for recommending community health nursing
      intervention.
AB  - Aim: This research study explored the lived experiences of adults diagnosed with
      Coronary Artery Disease (CAD) when exposed to a prolonged period of extreme cold.
      Design: This research study utilized descriptive qualitative research design.
      Methods: Face-to-face interview sessions with audio recording were conducted.
      There were 30 informants who participated in the study. Descriptive phenomenology
      with Colaizzi's method of data analysis was used. Results: Results revealed three
      themes, namely: (i) elucidating cold exposure; (ii) challenges of cold exposure;
      and (iii) translating adverse exposure to self-management. The results further
      revealed the significance of nursing health care especially to health promotion,
      disease prevention and health restoration especially in community setting.
      Conclusion: In conclusion, manifestations of CAD are triggered when exposed to a
      prolonged period of extremely low environmental temperature.

PMID- 29344397
TI  - A cross-sectional study of stress and its sources among health professional
      students at Makerere University, Uganda.
AB  - Aim: To assess prevalence of stress and its sources among undergraduate health
      professional students at Makerere University. Design: This was a descriptive
      cross-sectional study using quantitative methods of data collection. Methods: The
      study was conducted among 258 undergraduate health professional students
      (Medical, Dental and, Nursing students) at Makerere University. From each
      programme, students were recruited proportionately, while being selected
      conveniently from each year of study. Stress was measured using the General
      Health Questionnaire 12 and stressors assessed using a questionnaire developed
      from literature. After obtaining ethics approval, data were collected from
      consenting students. Data collected were analysed using SPSS statistical program.
      Results: The prevalence of stress was found to be 57.4% and stressors of academic
      and psychosocial origin were most frequently reported. The top stressors
      included; academic curriculum (38%), dissatisfaction with class lectures (30.9%),
      long distance walk (29.5%), lack of time for recreation (28.9%), performance in
      examination (28.3%), lack of special guidance from faculty (26.7%) and high
      parental expectations (26.7%).

PMID- 29344398
TI  - Exploring nurse managers' perception of using the RAFAELA system as a management
      tool in a Norwegian hospital setting.
AB  - Aim: The aim of the study, being part of a Norwegian evaluation project of the
      RAFAELA system, was to explore nurse managers' perception of the RAFAELA system
      as a management tool in a Norwegian hospital setting. Design: We applied an
      explorative qualitative design using focus group interviews. Methods: Two focus
      group interviews were performed with 12 nurses in different management positions
      during autumn 2013. The principles of qualitative content analysis were used for
      analysing data. Results: Three themes emerged. The informants experienced the
      RAFAELA system to be a basis for a precise and common langue. Furthermore, the
      informants considered it to be a system defining quality standards of nursing
      care. Finally, the RAFAELA system provided daily documentation of nursing
      intensity and thus was considered an important management tool for balancing
      patient needs with appropriate staff.

PMID- 29344399
TI  - Contested discourses and culture sensitivity: Norwegian nursing students'
      experience of clinical placement in Nicaragua.
AB  - Aim: The purpose of this study was to gain understanding of Norwegian students'
      practical experience of "culture sensitivity." Design: Using focus-group
      interviews and individual written assignments, we draw on a Foucauldian-inspired
      approach to analyse nursing students' narratives about their clinical placement
      in Nicaragua. Method: Seven third-year bachelor nursing students enrolled in a
      clinical placement programme on the Caribbean coast in Nicaragua and participated
      in focus-group interviews. Interviews were conducted prior to their departure to
      Nicaragua and after their return to Norway. Other sources of data included
      learning objectives for clinical placement, written individual assignments with
      students' reflections about their experiences and achievement of learning
      objectives. Results: Students expressed gradually increased awareness about the
      nursing discourses and power relations shaping clinical encounters throughout
      their learning trajectory in clinical placement. They became more aware of the
      politics of nursing practices through their experiences of clashes between
      different nursing discourses.

PMID- 29344400
TI  - The nursing legacy of the Korea Sisters.
AB  - Aim: During the Korean War (1950-1953), the Norwegian government sent a Mobile
      Army Surgical Hospital (MASH) to support the efforts of the United Nations (UN)
      Army. During the war, 111 Norwegian nurses served in seven contingents, each 6
      month, at the Norwegian Field Hospital in Korea. The nurses were nicknamed "The
      Korea Sisters". The aim of this study is to explore the impact and influence of
      their wartime nursing on Norwegian post-Korean-War nursing. Design: Qualitative.
      Methods: The study uses several historical research approaches. Interview,
      archival search, search in nursing periodicals, contemporary magazines and
      nursing text books. Result: The nursing legacy of The Korea Sisters can be found
      in changes in general nursing, uniform education of theatre nurses, uniform
      education of anaesthetist nurses and in humanitarian work.

PMID- 29344401
TI  - Protocol for Moving On: a randomized controlled trial to increase outcome
      expectations and exercise among breast cancer survivors.
AB  - Aim: The aim of this study was to test the feasibility and fidelity of an
      intervention, Moving On, aimed to increase outcome expectations OEs (i.e. what
      one expects to obtain or avoid as a result of a behaviour) and exercise among
      breast cancer survivors. Design: Randomized controlled trial. Methods:
      Intervention arm participants will be given a theory-guided booklet that was co
      created by the research team and three physically active breast cancer survivors
      who exercise to manage late and long-term treatment effects. Attention control
      arm participants will be given a similar booklet focused on diet. Participants
      will have 1 week to complete reading, writing and reflecting activities in the
      booklets. Study outcomes will be measured through online surveys; exercise will
      also be measured objectively with a Fitbit(r). Four weeks postintervention,
      participants' thoughts about the usefulness, strengths and weakness of the
      intervention booklet will be assessed. OEs and exercise will be measured at
      baseline, 4-, 8- and 12-week postintervention.

PMID- 29344402
TI  - Young Asian men with diabetes have the highest risk for acute coronary events:
      retrospective cohort analyses.
AB  - Objective: To understand the ethnic differences in coronary heart disease risk
      among inpatients with diabetes following acute coronary syndrome. Design: Single
      centre retrospective cohort-analysis of patients with type II diabetes over a six
      year period receiving standard care. Setting: Birmingham, UK. Participants: One
      thousand and one hundred and five patients with type II diabetes from a multi
      ethnic background. Main outcome measures: Odds ratios of coronary heart disease
      events among three ethnic groups. Results: The prevalence of coronary heart
      disease events was 20.7% in Asian, 13.2% in Caucasian and 7.7% in Afro-Caribbean
      patients. Asian patients were younger at diagnosis of diabetes (-5.1 years p <
      0.001 versus Afro-Caribbeans and -7.1 years p < 0.001 versus Caucasians). The
      mean number of events was highest amongst Asian (1.2) compared to Caucasian (1.1)
      and Afro-Caribbean (1.0) patients (p = 0.04). The mean age at first event was
      61.3 years for Asians, 62.5 years and 65.8 for Afro-Caribbeans and Caucasians,
      respectively (analysis of variance F[2,131] = 2.36 p = 0.09). Un-adjusted odds
      ratios for at least one coronary heart disease event were highest among Asian men
      (OR 5.04; 95% CI 2.31-11.01; p < 0.0001) with Afro-Caribbean women as baseline
      (OR 1.0). The odds ratios remain largely unchanged (1.0 Afro-Caribbeans
      [baseline], 1.27 [p = 0.56] Caucasians and 3.2 [p = 0.001] for Asians) when
      corrected for age, gender, duration of diabetes, insulin dependency, mean low
      density lipoprotein-cholesterol, triglycerides and high-density lipoprotein
      cholesterol, mean glycated haemoglobin, mean systolic and diastolic blood
      pressure (logistic regression; ROC: 79% AUC). Afro-Caribbean patients had the
      highest mean high-density lipoprotein-cholesterol (1.6 mmol/L) and the lowest
      risk for coronary heart disease events. Conclusions: Asian patients were younger
      at their first event and diagnosed earlier with diabetes. Asian men had the
      highest risk of coronary heart disease event which correlated with the lowest
      levels of high-density lipoprotein-cholesterol.

PMID- 29344403
TI  - Maternal morbidity and mortality associated with retroperitoneal haematomas in
      pregnancy.
AB  - Retroperitoneal haematomas in obstetrics are uncommon. The causes and
      pathogenesis of retroperitoneal haematomas lack clarity and the aim of this
      review is to recognise retroperitoneal haematomas as a separate entity from
      commonly seen vaginal and pelvic haematomas. It is time to raise awareness among
      obstetricians to recognise retroperitoneal haematomas as an important cause of
      maternal morbidity and mortality which requires high clinical suspicion and
      multidisciplinary input. As retroperitoneal haematomas are rare but can cause
      serious threat to maternal wellbeing, resources should be directed towards their
      management. Existing guidelines of maternal collapse and morbidity during
      pregnancy and puerperium need to include retroperitoneal haematomas as one of the
      important causes of maternal shock or morbidity. New learning pathways should be
      opted for to increase awareness of retroperitoneal haematomas among obstetricians
      enabling them to reflect on their implications while managing retroperitoneal
      haematomas. Management of retroperitoneal haematomas is complex and continues to
      improve with advancements in the investigative strategies, treatment options and
      multidisciplinary involvement.

PMID- 29344404
TI  - Unleashing the tiger - iatrogenic autoimmunity from cancer immunotherapy drugs.
AB  - Immune checkpoint inhibitors can lead to the development of organ and non-organ
      specific immune related adverse events.

PMID- 29344406
TI  - Research protocol: investigating the feasibility of a group self-management
      intervention for stroke (the GUSTO study).
AB  - Background: Life after stroke can be an ongoing struggle with over half of all
      survivors reporting unmet emotional and social needs. In the United Kingdom's
      (UK) national clinical guidelines for stroke, self-management is suggested as one
      approach which can support long-term needs. In the UK NHS, self-management
      interventions are delivered in various ways. Regardless of the delivery
      mechanism, a tailored approach and ways to integrate peer support are advocated.
      Group delivery offers a platform for peer support and has the potential to remain
      individualised. However, before the efficacy of a group self-management
      intervention can be tested, the feasibility must be explored. This research
      investigates the feasibility of a GroUp Self-management intervention for sTrOke
      (GUSTO). Methods: A randomised waitlist control design will be used to
      investigate the feasibility of a group self-management intervention adapted from
      an existing one-to-one intervention called Bridges. A mixed methods approach will
      be used. Qualitative work will capture participant experience, while quantitative
      work will allow preliminary comparison between the intervention and waitlist
      groups (between subjects) and pre-post intervention measures (within subjects).
      Interviews will be conducted with stroke survivors and focus groups with family
      and friends to assess acceptability of the intervention. Discussion: There is a
      growing interest in group-based self-management interventions for stroke as a
      method of supporting stroke survivors' ongoing unmet needs. This is an area with
      limited research to date. This study will inform design of a fully powered trial
      which would assess the efficacy of a group self-management intervention following
      stroke. Trial registration: ISRCTN19867168.

PMID- 29344405
TI  - Lee Silverman Voice Treatment versus standard speech and language therapy versus
      control in Parkinson's disease: a pilot randomised controlled trial (PD COMM
      pilot).
AB  - Background: Speech-related problems are common in Parkinson's disease (PD), but
      there is little evidence for the effectiveness of standard speech and language
      therapy (SLT) or Lee Silverman Voice Treatment (LSVT LOUD(r)). Methods: The PD
      COMM pilot was a three-arm, assessor-blinded, randomised controlled trial (RCT)
      of LSVT LOUD(r), SLT and no intervention (1:1:1 ratio) to assess the feasibility
      and to inform the design of a full-scale RCT. Non-demented patients with
      idiopathic PD and speech problems and no SLT for speech problems in the past 2
      years were eligible. LSVT LOUD(r) is a standardised regime (16 sessions over 4
      weeks). SLT comprised individualised content per local practice (typically weekly
      sessions for 6-8 weeks). Outcomes included recruitment and retention, treatment
      adherence, and data completeness. Outcome data collected at baseline, 3, 6, and
      12 months included patient-reported voice and quality of life measures, resource
      use, and assessor-rated speech recordings. Results: Eighty-nine patients were
      randomised with 90% in the therapy groups and 100% in the control group
      completing the trial. The response rate for Voice Handicap Index (VHI) in each
      arm was >= 90% at all time-points. VHI was highly correlated with the other
      speech-related outcome measures. There was a trend to improvement in VHI with
      LSVT LOUD(r) (difference at 3 months compared with control: - 12.5 points; 95% CI
      - 26.2, 1.2) and SLT (difference at 3 months compared with control: - 9.8 points;
      95% CI - 23.2, 3.7) which needs to be confirmed in an adequately powered trial.
      Conclusion: Randomisation to a three-arm trial of speech therapy including a no
      intervention control is feasible and acceptable. Compliance with both
      interventions was good. VHI and other patient-reported outcomes were relevant
      measures and provided data to inform the sample size for a substantive trial.
      Trial registration: International Standard Randomised Controlled Trial Number
      Register: ISRCTN75223808. registered 22 March 2012.

PMID- 29344407
TI  - TPF induction chemotherapy increases PD-L1 expression in tumour cells and immune
      cells in head and neck squamous cell carcinoma.
AB  - Background: Antiprogrammed cell death-1/programmed cell death-ligand 1 (PD-1/PD
      L1) therapies have demonstrated promising activity in advanced head and neck
      squamous cell carcinoma (HNSCC), with overall response rates of approximately 20%
      in unselected populations and survival benefit. Whether induction docetaxel,
      platinum and fluorouracil (TPF) modifies PD-L1 expression or tumour immune
      infiltrates is unknown. Patients and methods: Patients with locally advanced
      HNSCC treated at Gustave Roussy (Villejuif, France) between 2006 and 2013 by
      induction TPF followed by surgery were retrospectively considered. Patients with
      paired samples (pre-TPF and post-TPF) were kept for further analysis. PD-L1
      expression was quantified by immunohistochemistry according to a validated
      protocol. The objective of the study was to compare PD-L1 expression on tumour
      cells (TC) and immune cells (IC) (positivity threshold of >=5%) before and after
      TPF. CD8+ and Foxp3+ lymphocytes densities before and after TPF were also
      quantified. Results: Out of 313 patients receiving induction TPF, 86 underwent
      surgery; paired samples were available for 21 of them. Baseline PD-L1 expression
      was >=5% in two and five samples for TC and IC, respectively. A significant
      increase of PD-L1 expression was observed after TPF, with 15 samples (71%)
      presenting a positive staining in IC after induction chemotherapy (P=0.003;
      Wilcoxon rank-sum test) and eight samples (38%) in TC (P=0.005; Wilcoxon rank-sum
      test). Tumour-infiltrating CD8+ mean densities also significantly increased post
      TPF (P=0.01). There was no significant difference in Foxp3+ expression, CD8/Foxp3
      ratio or correlation with outcome. Conclusion: TPF induction chemotherapy in
      advanced HNSCC increases PD-L1 positivity on tumour-infiltrating ICs, as well as
      CD8+ lymphocytes density. These results warrant independent validation on larger
      datasets and might help therapeutic strategy in advanced HNSCC.

PMID- 29344408
TI  - Differential research impact in cancer practice guidelines' evidence base:
      lessons from ESMO, NICE and SIGN.
AB  - Background: This is an appraisal of the impact of cited research evidence
      underpinning the development of cancer clinical practice guidelines (CPGs) by the
      professional bodies of the European Society for Medical Oncology (ESMO), the
      National Institute for Health and Care Excellence (NICE) and the Scottish
      Intercollegiate Guidelines Network (SIGN). Methods: A total of 101 CPGs were
      identified from ESMO, NICE and SIGN websites across 13 cancer sites. Their 9486
      cited references were downloaded from the Web of Science Clarivate Group
      database, analysed on Excel (2016) using Visual Basic Application macros and
      imported onto SPSS (V.24.0) for statistical tests. Results: ESMO CPGs mostly
      cited research from Western Europe, while the NICE and SIGN ones from the UK,
      Canada, Australia and Scandinavian countries. The ESMO CPGs cited more recent and
      basic research (eg, drugs treatment), in comparison with NICE and SIGN CPGs where
      older and more clinical research (eg, surgery) papers were referenced. This
      chronological difference in the evidence base is also in line with that ESMO has
      a shorter gap between the publication of the research and its citation on the
      CPGs. It was demonstrated that ESMO CPGs report more chemotherapy research, while
      the NICE and SIGN CPGs report more surgery, with the results being statistically
      significant. Conclusions: We showed that ESMO, NICE and SIGN differ in their
      evidence base of CPGs. Healthcare professionals should be aware of this
      heterogeneity in effective decision-making of tailored treatments to patients,
      irrespective of geographic location across Europe.

PMID- 29344409
TI  - Immunotherapy in lung cancer.

PMID- 29344410
TI  - Traditional Chinese Medicine and Aging Intervention.

PMID- 29344411
TI  - Emerging Roles of Ganoderma Lucidum in Anti-Aging.
AB  - Ganoderma lucidum is a white-rot fungus that has been viewed as a traditional
      Chinese tonic for promoting health and longevity. It has been revealed that
      several extractions from Ganoderma lucidum, such as Ethanol extract, aqueous
      extract, mycelia extract, water soluble extract of the culture medium of
      Ganoderma lucidum mycelia, Ganodermasides A, B, C, D, and some bioactive
      components of Ganoderma lucidum, including Reishi Polysaccharide Fraction 3,
      Ganoderma lucidum polysaccharides I, II, III, IV, Ganoderma lucidum peptide,
      Ganoderma polysaccharide peptide, total G. lucidum triterpenes and Ganoderic acid
      C1 could exert lifespan elongation or related activities. Although the use of
      Ganoderma lucidum as an elixir has been around for thousands of years, studies
      revealing its effect of lifespan extension are only the tip of the iceberg.
      Besides which, the kinds of extractions or components being comfrimed to be anti
      aging are too few compared with the large amounts of Ganoderma lucidum
      extractions or constituients being discovered. This review aims to lay the ground
      for fully elucidating the potential mechanisms of Ganoderma lucidum underlying
      anti-aging effect and its clinical application.

PMID- 29344412
TI  - Ginseng: An Nonnegligible Natural Remedy for Healthy Aging.
AB  - Aging is an irreversible physiological process that affects all humans. Numerous
      theories have been proposed to regarding the process from a Western medicine
      perspective; however, ancient Chinese medicine practices and theories have
      increasingly gained attention, particularly ginseng, a grass that has been
      studied for the anti-aging properties of its active constituents. This review
      seeks to analyze current data on ginseng and its anti-aging properties. The plant
      species, characteristics, and active ingredients will be introduced. The main
      part of this review is focused on ginseng and its active components with regards
      to their effects on prolonging lifespan, the regulation of multiple organ systems
      including cardiovascular, nervous, immune, and skin, as well as the anti-oxidant
      and anti-inflammatory properties. The molecular mechanisms of these properties
      elucidated via various studies are summarized as further evidence of the anti
      aging effects of ginseng.

PMID- 29344413
TI  - Therapeutic Potential and Cellular Mechanisms of Panax Notoginseng on Prevention
      of Aging and Cell Senescence-Associated Diseases.
AB  - Owing to a dramatic increase in average life expectancy, most countries in the
      world are rapidly entering an aging society. Therefore, extending health span
      with pharmacological agents targeting aging-related pathological changes, are now
      in the spotlight of gerosciences. Panax notoginseng (Burk.) F. H. Chen, a species
      of the genus Panax, has been called the "Miracle Root for the Preservation of
      Life," and has long been used as a Chinese herb with magical medicinal value.
      Panax notoginseng has been extensively employed in China to treat
      microcirculatory disturbances, inflammation, trauma, internal and external
      bleeding due to injury, and as a tonic. In recent years, with the deepening of
      the research pharmacologically, many new functions have been discovered. This
      review will introduce its pharmacological function on lifespan extension, anti
      vascular aging, anti-brain aging, and anti-cancer properties, aiming to lay the
      ground for fully elucidating the potential mechanisms of Panax notoginseng's anti
      aging effect to promote its clinical application.

PMID- 29344414
TI  - Herba Cistanches: Anti-aging.
AB  - The Cistanche species ("Rou Cong Rong" in Chinese) is an endangered wild species
      growing in arid or semi-arid areas. The dried fleshy stem of Cistanches has been
      used as a tonic in China for many years. Modern pharmacological studies have
      since demonstrated that Herba Cistanches possesses broad medicinal functions,
      especially for use in anti-senescence, anti-oxidation, neuroprotection, anti
      inflammation, hepatoprotection, immunomodulation, anti-neoplastic, anti
      osteoporosis and the promotion of bone formation. This review summarizes the up
      to-date and comprehensive information on Herba Cistanches covering the aspects of
      the botany, traditional uses, phytochemistry and pharmacology, to lay ground for
      fully elucidating the potential mechanisms of Herba Cistanches' anti-aging effect
      and promote its clinical application as an anti-aging herbal medicine.

PMID- 29344415
TI  - Rhizoma Coptidis and Berberine as a Natural Drug to Combat Aging and Aging
      Related Diseases via Anti-Oxidation and AMPK Activation.
AB  - Aging is the greatest risk factor for human diseases, as it results in cellular
      growth arrest, impaired tissue function and metabolism, ultimately impacting life
      span. Two different mechanisms are thought to be primary causes of aging. One is
      cumulative DNA damage induced by a perpetuating cycle of oxidative stress; the
      other is nutrient-sensing adenosine monophosphate-activated protein kinase (AMPK)
      and rapamycin (mTOR)/ ribosomal protein S6 (rpS6) pathways. As the main bioactive
      component of natural Chinese medicine rhizoma coptidis (RC), berberine has
      recently been reported to expand life span in Drosophila melanogaster, and
      attenuate premature cellular senescence. Most components of RC including
      berberine, coptisine, palmatine, and jatrorrhizine have been found to have
      beneficial effects on hyperlipidemia, hyperglycemia and hypertension aging
      related diseases. The mechanism of these effects involves multiple cellular
      kinase and signaling pathways, including anti-oxidation, activation of AMPK
      signaling and its downstream targets, including mTOR/rpS6, Sirtuin1/ forkhead box
      transcription factor O3 (FOXO3), nuclear factor erythroid-2 related factor-2
      (Nrf2), nicotinamide adenine dinucleotide (NAD+) and nuclear factor-kappaB (NF
      kappaB) pathways. Most of these mechanisms converge on AMPK regulation on
      mitochondrial oxidative stress. Therefore, such evidence supports the possibility
      that rhizoma coptidis, in particular berberine, is a promising anti-aging natural
      product, and has pharmaceutical potential in combating aging-related diseases via
      anti-oxidation and AMPK cellular kinase activation.

PMID- 29344416
TI  - Lycium Barbarum: A Traditional Chinese Herb and A Promising Anti-Aging Agent.
AB  - Lycium barbarum has been used in China for more than 2,000 years as a traditional
      medicinal herb and food supplement. Lycium barbarum contains abundant Lycium
      barbarum polysaccharides (LBPs), betaine, phenolics, carotenoids (zeaxanthin and
      beta-carotene), cerebroside, 2-O-beta-d-glucopyranosyl-l-ascorbic acid (AA
      2betaG), beta-sitosterol, flavonoids and vitamins (in particular, riboflavin,
      thiamine, and ascorbic acid). LBPs are the primary active components of Lycium
      barbarum. In this review, we discuss the pharmacological activities of LBPs and
      other major components. They have been reported to mediate significant anti-aging
      effects, through antioxidant, immunoregulative, anti-apoptotic activities and
      reducing DNA damage. Thus, the basic scientific evidence for anti-aging effects
      of LBPs is already available. However, additional studies are needed to
      understand mechanisms by which LBPs mediate anti-aging properties. Novel findings
      from such studies would likely pave the way for the clinical application of
      traditional chinese medicine Lycium barbarum in modern evidence-based medicine.

PMID- 29344417
TI  - The Effect of Traditional Chinese Medicine on Neural Stem Cell Proliferation and
      Differentiation.
AB  - Neural stem cells (NSCs) are special types of cells with the potential for self
      renewal and multi-directional differentiation. NSCs are regulated by multiple
      pathways and pathway related transcription factors during the process of
      proliferation and differentiation. Numerous studies have shown that the compound
      medicinal preparations, single herbs, and herb extracts in traditional Chinese
      medicine (TCM) have specific roles in regulating the proliferation and
      differentiation of NSCs. In this study, we investigate the markers of NSCs in
      various stages of differentiation, the related pathways regulating the
      proliferation and differentiation, and the corresponding transcription factors in
      the pathways. We also review the influence of TCM on NSC proliferation and
      differentiation, to facilitate the development of TCM in neural regeneration and
      neurodegenerative diseases.

PMID- 29344418
TI  - Advances in the Studies of Ginkgo Biloba Leaves Extract on Aging-Related
      Diseases.
AB  - The prevalence of degenerative disorders in public health has promoted in-depth
      investigations of the underlying pathogenesis and the development of new
      treatment drugs. Ginkgo biloba leaves extract (EGb) is obtained from Ginkgo
      biloba leaves and has been used for thousands of years. In recent decades, both
      basic and clinical studies have established the effects of EGb. It is widely used
      in various degenerative diseases such as cerebrovascular disease, Alzheimer's
      disease, macroangiopathy and more. Here, we reviewed several pharmacological
      mechanisms of EGb, including its antioxidant properties, prevention of
      mitochondrial dysfunctions, and effect on apoptosis. We also described some
      clinical applications of EGb, such as its effect on neuro and cardiovascular
      protection, and anticancer properties. The above biological functions of EGb are
      mainly focused on aging-related disorders, but its effect on other diseases
      remains unclear. Thus, through this review, we aim to encourage further studies
      on EGb and discover more potential applications.

PMID- 29344419
TI  - Dendrobium: Sources of Active Ingredients to Treat Age-Related Pathologies.
AB  - Dendrobium represents one of the most important orchid genera, ornamentally and
      medicinally. Dendrobiums are sympodial epiphytic plants, which is a name they are
      worthy of, the name coming from Greek origin: "dendros", tree, and "bios", life.
      Dendrobium species have been used for a thousand years as first-rate herbs in
      traditional Chinese medicine (TCM). They are source of tonic, astringent,
      analgesic, antipyretic, and anti-inflammatory substances, and have been
      traditionally used as medicinal herbs in the treatment of a variety of disorders,
      such as, nourishing the stomach, enhancing production of body fluids or
      nourishing Yin. The Chinese consider Dendrobium as one of the fifty fundamental
      herbs used to treat all kinds of ailments and use Dendrobium tonic for longevity.
      This review is focused on main research conducted during the last decade (2006
      2016) on Dendrobium plants and their constituents, which have been subjected to
      investigations of their pharmacological effects involving anticancer, anti
      diabetic, neuroprotective and immunomodulating activities, to report their
      undeniable potential for treating age-related pathologies.

PMID- 29344420
TI  - The Effects of Baicalin and Baicalein on Cerebral Ischemia: A Review.
AB  - Ischemic stroke, producing a high mortality and morbidity rate, is a common
      clinical disease. Enhancing the prevention and control of ischemic stroke is
      particularly important. Baicalin and its aglycon baicalein are flavonoids
      extracted from Scutellaria baicalensis, an important traditional Chinese herb. In
      recent years, a growing body of evidences has shown that baicalin and baicalein
      could be effective in the treatment of cerebral ischemia. Pharmacokinetic studies
      have shown that baicalin could penetrate the blood-brain barrier and distribute
      in cerebral nuclei. Through a variety of in vitro and in vivo models of ischemic
      neuronal injury, numerous studies have demonstrated that baicalin and baicalein
      have salutary effect for neuroprotection. Especially, the studies on the
      pharmacological mechanism showed that baicalin and baicalein have several
      pharmacological activities, which include antioxidant, anti-apoptotic, anti
      inflammatory and anti-excitotoxicity effects, protection of the mitochondria,
      promoting neuronal protective factors expression and adult neurogenesis effects
      and many more. This review focuses on the neuroprotective effects of baicalin and
      baicalein in ischemia or stroke-induced neuronal cell death. We aimed at
      collecting all important information regarding the neuroprotective effect and its
      pharmacological mechanism of baicalin and baicalein in various in vivo and in
      vitro experimental models of ischemic neuronal injury.

PMID- 29344422
TI  - The Effects of Physical Training are Varied and Occur in an Exercise Type
      Dependent Manner in Elderly Men.
AB  - Regular exercise can decrease the deleterious effects of aging and limit the
      development and progression of chronic disease in elderly people, depending on
      the type, intensity, frequency, and duration of exercise. This study aimed to
      investigate the potential protective effects of different physical training
      programs on oxidative stress parameters and inflammatory and neurotrophic
      mediators in the serum of elderly men. Healthy male volunteers [60 to 80 years;
      n=55] were divided into four groups: control [Ctr, n=14], aerobic training on dry
      land [ATdl, n=12]; and combined training on dry land [CTdl, n=12] or in water
      [CTw, n=17]. The training protocols were performed over 8 weeks, three times per
      week. Each 1 h session included 5 min warming-up exercise, 50 min specific
      training [aerobic, strength, or combined], and 5 min stretching. Blood samples
      were drawn 72 h before [baseline] the beginning of the 8 weeks' protocol and 48 h
      after the last training session, processed, and the serum was aliquoted and
      stored at -70  degrees C until biochemical assessment of oxidative damage,
      antioxidant system and neurotrophic, growth and inflammatory factors. Elevated
      BDNF or IGF-1 levels were observed in the ATdl or CTdl groups, respectively.
      Overall oxidative stress parameters were improved including reduced lipid
      oxidative damage and increased thioredoxin reductase and glutathione peroxidase
      activities and total glutathione. Significant decreases in the inflammatory
      mediators IL-6 and IL-8 were observed; IL-6 was more susceptible to the effects
      of type of physical training. Thus, the effects of training in elderly men vary
      in an exercise type-dependent manner.

PMID- 29344424
TI  - Letters to the Editor.

PMID- 29344423
TI  - Age-Related Gray and White Matter Changes in Normal Adult Brains.
AB  - Normal aging is associated with both structural changes in many brain regions and
      functional declines in several cognitive domains with advancing age. Advanced
      neuroimaging techniques enable explorative analyses of structural alterations
      that can be used as assessments of such age-related changes. Here we used voxel
      based morphometry (VBM) to investigate regional and global brain volume
      differences among four groups of healthy adults from the IXI Dataset: older
      females (OF, mean age 68.35 yrs; n=69), older males (OM, 68.43 yrs; n=66), young
      females (YF, 27.09 yrs; n=71), and young males (YM, 27.91 yrs; n=71), using 3D T1
      weighted MRI data. At the global level, we investigated the influence of age and
      gender on brain volumes using a two-way analysis of variance. With respect to
      gender, we used the Pearson correlation to investigate global brain volume
      alterations due to age in the older and young groups. At the regional level, we
      used a flexible factorial statistical test to compare the means of gray matter
      (GM) and white matter (WM) volume alterations among the four groups. We observed
      different patterns in both the global and regional GM and WM alterations in the
      young and older groups with respect to gender. At the global level, we observed
      significant influences of age and gender on global brain volumes. At the regional
      level, the older subjects showed a widespread reduction in GM volume in regions
      of the frontal, insular, and cingulate cortices compared to the young subjects in
      both genders. Compared to the young subjects, the older subjects showed a
      widespread WM decline prominently in the thalamic radiations, in addition to
      increased WM in pericentral and occipital areas. Knowledge of these observed
      brain volume differences and changes may contribute to the elucidation of
      mechanisms underlying aging as well as age-related brain atrophy and disease.

PMID- 29344421
TI  - Anti-Aging Implications of Astragalus Membranaceus (Huangqi): A Well-Known
      Chinese Tonic.
AB  - Owing to a dramatic increase in average life expectancy and the Family Planning
      program of the 1970s - 1990s, China is rapidly becoming an aging society.
      Therefore, the investigation of healthspan-extending drugs becomes more urgent.
      Astragalus membranaceus (Huangqi) is a major medicinal herb that has been
      commonly used in many herbal formulations in the practice of traditional Chinese
      medicine (TCM) to treat a wide variety of diseases and body disorders, or
      marketed as life-prolonging extracts for human use in China, for more than 2000
      years. The major components of Astragalus membranaceus are polysaccharides,
      flavonoids, and saponins. Pharmacological research indicates that the extract
      component of Astragalus membranaceus can increase telomerase activity, and has
      antioxidant, anti-inflammatory, immunoregulatory, anticancer, hypolipidemic,
      antihyperglycemic, hepatoprotective, expectorant, and diuretic effects. A
      proprietary extract of the dried root of Astragalus membranaceus, called TA-65,
      was associated with a significant age-reversal effect in the immune system. Our
      review focuses on the function and the underlying mechanisms of Astragalus
      membranaceus in lifespan extension, anti-vascular aging, anti-brain aging, and
      anti-cancer effects, based on experimental and clinical studies.

PMID- 29344425
TI  - A Case of Psychosis in a Patient with Secondary Adrenal Insufficiency: A Possible
      Etiological Role of a Hypocortisolemic-induced Increase in Proinflammatory
      Cytokines.
AB  - Adrenal insufficiency is divided into three types based on the etiology of its
      development. In primary adrenal insufficiency, pathology resides in end-organ
      failure at the level of the adrenal cortex, while in secondary and tertiary
      adrenal insufficiency, impairment rests in the pituitary gland and hypothalamus,
      respectively. Regardless of etiology, adrenal insufficiency results in a
      hypocortisolemic condition. While the relationship between neuropsychiatric
      symptoms, especially psychosis, and hypercortisolemia has been extensively
      documented, the development of hypocortisolemia-induced psychosis is less common.
      We present a case of secondary adrenal insufficiency caused by a pituitary tumor.
      During the course of evaluation and treatment, the patient developed a psychotic
      episode. We will briefly review the condition of adrenal insufficiency and
      propose how hypocortisolemia can result in psychosis.

PMID- 29344426
TI  - ZIKA MICROCEPHALY.

PMID- 29344427
TI  - Top 10 Myths about Telepsychiatry.
AB  - This ongoing column is dedicated to providing information to our readers on
      managing legal risks associated with medical practice. We invite questions from
      our readers. The answers are provided by PRMS, Inc. (www.prms.com), a manager of
      medical professional liability insurance programs with services that include risk
      management consultation, education and onsite risk management audits, and other
      resources to healthcare providers to help improve patient outcomes and reduce
      professional liability risk. The answers published in this column represent those
      of only one risk management consulting company. Other risk management consulting
      companies or insurance carriers may provide different advice, and readers should
      take this into consideration. The information in this column does not constitute
      legal advice. For legal advice, contact your personal attorney. Note: The
      information and recommendations in this article are applicable to physicians and
      other healthcare professionals so "clinician" is used to indicate all treatment
      team members.

PMID- 29344428
TI  - Introduction to Special Issue: Disability, Work and Representation: New
      Perspectives.

PMID- 29344429
TI  - Pathway Analysis of Gene Expression of E14 Versus E18 Fetal Fibroblasts.
AB  - Objective: Fetuses early in gestation heal skin wounds without forming scars. The
      biological mechanisms behind this process are largely unknown. Fibroblasts,
      however, are cells known to be intimately involved in wound healing and scar
      formation. We examined fibroblasts in different stages of development to
      characterize differences in gene expression that may result in the switch from
      regenerative wound repair to repair with scarring. Approach: Fibroblasts were
      isolated and cultured from the back skin of BALB/c wild-type mouse fetuses at
      embryonic day (E)14 and E18 (n = 10). The fibroblast total RNA was extracted, and
      microarray analysis was conducted using chips containing 42,000 genes.
      Significance analysis of microarrays was performed to identify genes with greater
      than twofold expression difference and a false discovery rate of less than two.
      Identified genes subsequently underwent enrichment analysis to detect
      differentially expressed pathways. Results: Two hundred seventy-five genes were
      differentially expressed between E14 and E18 in fetal fibroblasts. Thirty genes
      were significantly downregulated and 245 genes were significantly upregulated at
      E18 compared with E14. Ingenuity pathway analysis identified the top 20 signaling
      pathways differentially activated in fetal fibroblasts between the E18 and E14
      time points. Innovation: To our knowledge, this work represents the first
      instance where differentially expressed genes and signaling pathways between
      fetal fibroblasts at E14 and E18 have been studied. Conclusion: The genes and
      pathways identified here potentially underlie the mechanism behind the transition
      from fetal wound healing via regeneration to wound healing by repair, and may
      prove to be key targets for future therapeutics.

PMID- 29344430
TI  - An Improved Humanized Mouse Model for Excisional Wound Healing Using Double
      Transgenic Mice.
AB  - Objective: Splinting full-thickness cutaneous wounds in mice has allowed for a
      humanized model of wound healing. Delineating the epithelial edge and assessing
      time to closure of these healing wounds via macroscopic visualization have
      remained a challenge. Approach: Double transgenic mice were created by
      crossbreeding K14-Cre and ROSAmT/mG reporter mice. Full-thickness excisional
      wounds were created in K14-Cre/ROSAmT/mG mice (n = 5) and imaged using both
      normal and fluorescent light on the day of surgery, and every other postoperative
      day (POD) until wound healing was complete. Ten blinded observers analyzed a
      series of images from a single representative healing wound, taken using normal
      or fluorescent light, to decide the POD when healing was complete. K14
      Cre/ROSAmT/mG mice (n = 4) were subsequently sacrificed at the four potential
      days of rated wound closure to accurately determine the histological point of
      wound closure using microscopic fluorescence imaging. Results: Average time to
      wound closure was rated significantly longer in the wound series images taken
      using normal light, compared with fluorescent light (mean POD 13.6 vs. 11.6, *p =
      0.008). Fluorescence imaging of histological samples indicated that
      reepithelialization was complete at 12 days postwounding. Innovation: We describe
      a novel technique, using double transgenic mice K14-Cre/ROSAmT/mG and
      fluorescence imaging, to more accurately determine the healing time of wounds in
      mice upon macroscopic evaluation. Conclusion: The accuracy by which wound healing
      can be macroscopically determined in vivo in mouse models of wound healing is
      significantly enhanced using K14-Cre/ROSAmT/mG double transgenic mice and
      fluorescence imaging.

PMID- 29344431
TI  - Noncoding RNAs in Wound Healing: A New and Vast Frontier.
AB  - Significance: Wound healing requires a highly orchestrated coordination of
      processes that are not yet fully understood. Therefore, available clinical
      therapies are thus far limited in their efficacy in preventing and treating both
      chronic wounds and scars. Current gene-based therapeutics is largely based on our
      understanding of the protein-coding genome and proteins involved in known wound
      healing pathways. Recent Advances: Noncoding RNAs such as microRNAs and long
      noncoding RNAs have recently been found to be significant modulators of gene
      expression in diverse cellular pathways. Research has now implicated noncoding
      RNAs in nearly every stage of the wound healing process, suggesting that they may
      serve as clinical therapeutic targets. Noncoding RNAs are critical regulators in
      processes such as angiogenesis and cutaneous cell migration and proliferation,
      including classically described biological pathways previously attributed to
      mostly protein constituents. Critical Issues: The complexity and diversity of the
      interactions of noncoding RNAs with their targets and other binding partners
      require thorough characterization and understanding of their functions before
      they may be altered to modulate human wound healing pathways. Future Directions:
      Research in the area of noncoding RNAs continues to rapidly expand our
      understanding of their potential roles in physiological and pathological wound
      healing. Coupled with improving technologies to enhance or suppress target
      noncoding RNA in vivo, these advances hold great promise in the development of
      new therapies for wound healing.

PMID- 29344433
TI  - One Click Away: Digital Mentorship in the Modern Era.
AB  - Mentorship is a valuable component of the career development of junior faculty.
      The digital era has allowed for greater access to mentors spanning geographic
      barriers and time zones. This article discusses the concept of digital
      mentorship, as well as strategies and techniques for developing and supporting a
      digital mentoring relationship in the modern era.

PMID- 29344432
TI  - WT1 peptide vaccine in Montanide in contrast to poly ICLC, is able to induce WT1
      specific immune response with TCR clonal enrichment in myeloid leukemia.
AB  - Background: The optimal strategy for vaccination to induce CD8+ T cell responses
      against WT1 is not known. Methods: A pilot randomized study in HLA-A02+ patients
      to receive vaccination with WT1 in Montanide or in poly ICLC, a TLR3 agonist, to
      explore the novel immune adjuvant was conducted. Seven patients were randomized.
      Four patients received WT1 in Montanide, and three with WT1 in poly ICLC. Five
      patients were in morphologic remission and two had residual morphologic disease
      at the study entry. Results: All patients finished the induction phase without
      any major toxicity except mild transient local injection reaction. One patient on
      the Montanide arm developed aseptic ulceration at two vaccine sites which healed
      without antibiotics. Three of 4 patients on the Montanide arm had a decreased
      expression of WT1 after WT1 vaccination, and two of them demonstrated generation
      of WT1-specific cytotoxic CD8+ T cell responses with biased TCR beta chain
      enrichment. In contrast, no obvious WT1-specific immune responses were detected
      in two patients on the poly ICLC arm, nor was there clonal enrichment by TCR
      alpha/beta sequencing; however, these patients did also have decreased WT1
      expression and remained in remission several years after the initiation of
      treatment. Conclusions: WT1 peptide vaccine with Montanide as an adjuvant induces
      detectable WT1-specific CD8+ T cell responses with clonal TCR enrichment, which
      may be capable of controlling leukemia recurrence in the setting of minimal
      residual disease. Poly ICLC may induce anti-leukemic activity in the absence of
      detectable WT1 specific CD8+ T cell responses.Trial registration NCT01842139,
      7/3/2012 retrospectively registered;
      https://clinicaltrials.gov/ct2/show/NCT01842139.

PMID- 29344434
TI  - Rare Multidrug-Resistant Pulmonary Nocardiosis in AIDS.
AB  - Nocardiosis is an opportunistic infection in patients with depressed cell
      mediated immunity. Inhalation is the primary route for exposure via dust
      particles. Patients with acquired immune deficiency syndrome (AIDS) are at
      increased risk of disseminated disease. A challenge in the diagnosis of pulmonary
      nocardiosis is that it can mimic other pulmonary diseases. Nocardia farcinica
      tends to be a more virulent, multidrug-resistant strain with an increased
      tendency to disseminate. This report describes a 64-year-old man with AIDS found
      to have pulmonary nocardiosis that did not respond to standard antibiotic
      therapy. Further evaluation revealed the virulent, multidrug-resistant Nocardia
      farcinica species. Targeted antibiotic therapy was initiated, after which the
      patient had an improvement in pulmonary symptoms. It is important to suspect
      pulmonary nocardiosis in immunocompromised patients who fail to respond to
      standard antimicrobial therapy. Susceptibilities should be obtained so that
      appropriate therapy can be promptly initiated as Nocardia farcinica is highly
      resistant to multiple antimicrobials.

PMID- 29344435
TI  - Synchronous Uterine Metastases from Breast Cancer: Case Study and Literature
      Review.
AB  - Breast cancer rarely metastasizes to the uterus. Here, we report two breast
      cancer patients with synchronous metastases to the uterus. Case 1 highlights a 46
      year-old female with invasive ductal carcinoma who presented with a breast mass
      and was found to have uterine enlargement on positron emission tomography (PET)
      scan. Biopsy revealed a metastatic 4 mm focus of breast cancer in the background
      of endometrial hyperplasia. Case 2 reports a 62-year-old postmenopausal female
      diagnosed with lobular carcinoma of the breast following an abnormal screening
      mammogram. A routine pap smear necessitated further workup, revealing
      simultaneous endometrial and cervical metastasis. Both patients did not have any
      gynecologic symptoms and presented a diagnostic challenge.

PMID- 29344436
TI  - Exploring Laser-Induced Breakdown Spectroscopy as a Potential Tool in Mohs
      Micrography: A Mini Review.
AB  - Mohs micrographic surgery is the technique of surgically removing skin tumors by
      gradually excising thin layers and visualizing under a microscope till a tumor
      free zone is obtained. During the surgical procedure, visible tumors are
      surgically removed. During the second stage, if tumor margins are clear with the
      positive specimen at depth, only depth cavitations need to be done without
      altering the tumor diameter. Defining the depth during this procedure is a major
      challenge due to the nonexistence of proper guidelines. Using the laser-induced
      breakdown spectroscopy (LIBS) technique, depth profiling can be performed
      precisely, preventing excessive tissue removal and reducing time consumption
      during the microscopic examination.

PMID- 29344437
TI  - Rhabdomyolysis in a Patient Taking Both Oxandrolone for Bodybuilding and
      Methamphetamine.
AB  - Nonprescription drug use is increasingly prevalent in the United States. We
      report a case of a 31-year-old male who presented with hallucinations and was
      found to have rhabdomyolysis. He was consuming oxandrolone for six weeks and
      ingested methamphetamine the night prior to presentation. With supportive
      treatment, including intravenous hydration, the patient's mental status returned
      to baseline and rhabdomyolysis resolved. Our case illustrates the need to
      understand the interaction between different illicit substances. More research
      needs to be done to further understand the reactions between different
      medications as patients consume different combinations of substances.

PMID- 29344440
TI  - HIV assessment and testing for hospital in-patients: still a weak link in the
      cascade.

PMID- 29344438
TI  - New Therapeutic Approaches in Obesity and Metabolic Syndrome Associated with
      Polycystic Ovary Syndrome.
AB  - Polycystic ovary syndrome (PCOS) is a pathophysiological disorder affecting
      reproductive and metabolic indices. PCOS is commonly associated with a high
      prevalence of insulin resistance and obesity; this association carries an
      increased risk of developing metabolic syndrome, type 2 diabetes mellitus (T2DM),
      and cardiovascular disease. Guidelines recommend lifestyle modification,
      metformin, hormonal contraceptives (HCs), and bariatric surgery as the main
      treatment options in obese patients with PCOS. Studies are being conducted to
      test the efficacy of existing treatment options as well as to discover new
      therapies. This review focuses on the most recent advances in this regard and
      highlights new hypotheses and emerging studies to give a picture of the latest
      therapeutic trends in the treatment of obese patients with PCOS. In this respect,
      much attention is given to the role of inositols, the mediators of insulin
      action. A deficiency of d-chiro-inositol containing inositol-phospho-glycans may
      be the basis of insulin resistance frequently seen in PCOS patients. Moreover,
      evidence suggests the use of statins in obese women with PCOS, but guidelines
      call for further research. Adiponectin, quercetin, vitamin D, and anti-obesity
      drugs have also been studied and seem to have a useful role in the treatment of
      obesity and metabolic syndrome in PCOS. Many trials have been conducted on the
      use of non-pharmacological therapies. Therapies including resveratrol,
      acupuncture, and berberine have favorable effects in overweight PCOS patients.
      However, more research is needed to reveal the clinical complexity of PCOS and
      develop more effective treatment options.

PMID- 29344441
TI  - Protecting those who care for others.

PMID- 29344439
TI  - Regiochemical Control in Triptycene Formation-An Exercise in Subtle Balancing
      Multiple Factors.
AB  - Reactions between 1,8-dichloroanthracenes with substituents in position 10 and
      ortho-chloroaryne afford mixtures of 1,8,13- (syn) and 1,8,16
      trichlorotriptycenes (anti). The syn/anti ratio is dependent on these
      substituents. Electropositive substituents like SiMe3 and GeMe3 lead to preferred
      formation of the syn-isomer, whereas CMe3 groups exclusively afford the anti
      isomer. Different quantum chemical calculations including location of transition
      states give conflicting results, but indicate the importance of dispersion forces
      for an at least qualitative prediction of results. The syn-trichlorotriptycenes
      with SiMe3 and GeMe3 substituents were characterized by using NMR spectroscopy,
      mass spectrometry, and X-ray diffraction experiments.

PMID- 29344442
TI  - Active tuberculosis case finding in India: need for introspection.

PMID- 29344443
TI  - Outcomes of patients treated with individualised anti-tuberculosis regimens in a
      tertiary care centre in India.

PMID- 29344444
TI  - Addressing deprivation of liberty, human mobility and tuberculosis in 2018.

PMID- 29344446
TI  - Global Optimal PEEP for Anesthetized Patients.

PMID- 29344445
TI  - Comparing Postoperative Complications and Inflammatory Markers Using Total
      Intravenous Anesthesia Versus Volatile Gas Anesthesia for Pancreatic Cancer
      Surgery.
AB  - Objectives: The objective of this study is to evaluate postoperative
      complications and inflammatory profiles when using a total intravenous anesthesia
      (TIVA) or volatile gas-opioid (VO) based anesthesia in patients undergoing
      pancreatic cancer surgery. Methods: Design, retrospective propensity score
      matched cohort; Setting, major academic cancer hospital; Patients, all patients
      who had pancreatic surgery between November 2011 and August 2014 were
      retrospectively reviewed. Propensity score matched patient pairs were formed. A
      total of 134 patients were included for analysis with 67 matched pairs;
      Interventions, Patients were categorized according to type of anesthetic used
      (TIVA or VO). Patients in the TIVA group received preoperative celecoxib,
      tramadol, and pregabalin in addition to intraoperative TIVA with propofol,
      lidocaine, ketamine, and dexmedetomidine. The VO-group received a volatile-opioid
      based anesthetic; Measurements, demographic, perioperative clinical data,
      platelet lymphocyte ratios, and neutrophil lymphocyte ratios were collected.
      Complications were graded and collected prospectively and later reviewed
      retrospectively. Results: Patients receiving TIVA were more likely to have no
      complication or a lower grade complication than the VO-group (P = 0.014). There
      were no differences in LOS or postoperative inflammatory profiles noted between
      the TIVA and VO groups. Conclusions: In this retrospective matched analysis of
      patients undergoing pancreatic cancer surgery, TIVA was associated with lower
      grade postoperative complications. Length of hospital stay (LOS) and
      postoperative inflammatory profiles were not significantly different.

PMID- 29344447
TI  - Successful Management of Right Ventricular Perforation Associated with a
      Pacemaker Lead During Off-Pump CABG Surgery: A Case Report.
AB  - Introduction: Intraoperative right ventricular perforation due to pacing catheter
      after its successful and uneventful insertion is a rare complication. Here, we
      present a case of cardiac arrest due to right ventricular perforation associated
      with a pacemaker lead during off-pump coronary artery bypass graft surgery. Case
      Presentation: The case was a 68-year-old male, who was admitted to our hospital
      with retrosternal chest pain. He had a history of implantation of a permanent
      pacemaker due to symptomatic complete atrioventricular block. Based on
      angiography, the diagnosis was 3- vessel disease involving the left anterior
      descending, second obtuse marginal, and right coronary arteries. The right
      ventricle was perforated by the tip of the permanent pacemaker lead during off
      pump coronary artery bypass graft surgery. Subsequently, the patient suddenly
      experienced cardiac arrest and underwent emergency on-pump cardiac surgery.
      Conclusions: This case showed that in some situations, emergency surgery as a
      life saving procedure may be required in cardiac perforation due to permanent
      pacemaker lead even following cardiac arrest.

PMID- 29344448
TI  - Learning Theories: The Basics to Learn in Medical Education.

PMID- 29344449
TI  - Motivating Students for Project-based Learning for Application of Research
      Methodology Skills.
AB  - Introduction: Project-based learning (PBL) is motivational for students to learn
      research methodology skills. It is a way to engage and give them ownership over
      their own learning. Aims and Objectives: The aim of this study is to use PBL for
      application of research methodology skills for better learning by encouraging an
      all-inclusive approach in teaching and learning rather than an individualized
      tailored approach. Methodology: The present study was carried out for MBBS 6th-
      and 7th-semester students of community medicine. Students and faculties were
      sensitized about PBL and components of research methodology skills. They worked
      in small groups. The students were asked to fill the student feedback
      Questionnaire and the faculty was also asked to fill the faculty feedback
      Questionnaire. Both the Questionnaires were assessed on a 5 point Likert scale.
      After submitted projects, document analysis was done. Results: A total of 99
      students of the 6th and 7th semester were participated in PBL. About 90.91%
      students agreed that there should be continuation of PBL in subsequent batches.
      73.74% felt satisfied and motivated with PBL, whereas 76.77% felt that they would
      be able to use research methodology in the near future. Conclusions: PBL requires
      considerable knowledge, effort, persistence, and self-regulation on the part of
      the students. They need to devise plans, gather information evaluate both the
      findings, and their approach. Facilitator plays a critical role in helping
      students in the process by shaping opportunity for learning, guiding students,
      thinking, and helping them construct new understanding.

PMID- 29344450
TI  - Hybrid Tool for Assessment of Professionalism among Dental Undergraduate
      Students.
AB  - Context: Of the several methods available for assessment of professionalism,
      there is still no consensus on an ideal tool for dental undergraduate (UG)
      students. Aims: The study aims to use a hybrid tool for assessment of
      professionalism among dental undergraduate students. Settings and Design: Cross
      sectional design with purposive sampling. Subjects and Methods: All final year UG
      dental students participated in this study. Evaluation of knowledge about
      professionalism was through written test. Professional behavior of each final
      year student in a clinical setting was assessed with a prevalidated questionnaire
      of multisource feedback (MSF). The scores of written test and the MSF were
      calculated for each student. Data were analyzed to evaluate scores of knowledge
      and MSF scores as per assessor category. Correlation between knowledge scores and
      MSF was evaluated. Student perceptions were taken toward assessment of
      professionalism. Statistical Analysis Used: Statistical analysis was done using
      descriptive statistics. Pearson's coefficient was used to determine the
      correlation between average knowledge scores and the MSF scores. Results:
      Knowledge scores were significantly more for female students (P < 0.05, t-test).
      Patients rated the students highest. Correlation between knowledge and MSF scores
      was found to be statistically significant (Pearson's correlation, P < 0.01).
      Students gave feedback that assessment of professionalism should be done from the
      beginning of the clinical years. Conclusions: Evaluation revealed that knowledge
      toward professionalism correlated with the professional behavior implying
      association between knowledge and reasons for a particular action.

PMID- 29344451
TI  - Evaluation of Brainstorming Session as a Teaching-learning Tool among
      Postgraduate Medical Biochemistry Students.
AB  - Background: The thrust for postgraduate teaching should be self-directed learning
      with equal participation by all students in academic discussions. Group
      discussions involve conduction of the discourse by a leader who guides the
      discussion as well as points out any wrong information. This discourages quieter
      students from participation with the fear of rebuke. Brainstorming is devoid of
      all such fallacies with no judgment and reprimand. Aim: The aim of this study was
      to use brainstorming as a teaching-learning tool among postgraduate students of
      medical biochemistry. Materials and Methods: The project was commenced after due
      approvals from the research and ethical committee. The participants were enrolled
      after informed consent and sensitization. All the pro forma and questionnaires
      were duly validated by experts. After piloting and incorporation of the
      suggestions for improvisation, the main sessions were planned and implemented.
      The response was judged by posttest scores and feedback forms. Results: There was
      an improvement of understanding of the biochemical concepts as assessed by the
      posttest scores and solving of a similar clinical problem. The students expressed
      satisfaction with the conduction, timing, and discussion of the clinical
      problems. The drawbacks of traditional teaching as expressed during the feedback
      stage were also taken care of by the brainstorming sessions. Conclusions: Our
      project made the students and the faculty aware about the utility of
      brainstorming for teaching purposes in medical education which till now was
      considered efficacious only for troubleshooting in advertising and management
      institutions. The students were satisfied with this technique for understanding
      of biochemical concepts.

PMID- 29344452
TI  - The Acceptability and Feasibility of Mini-clinical Evaluation Exercise as a
      Learning Tool for Pediatric Postgraduate Students.
AB  - Background: The mini-clinical evaluation exercise (Mini-CEX) is a valid and
      reliable tool that facilitates the assessment of skills essential for a physician
      and provision of immediate feedback. Aims: This study aimed to assess the
      acceptability and feasibility of Mini-CEX as a learning tool for pediatric
      residents. Materials and Methods: Following the sensitization with the concept of
      Mini-CEX, the actual process of assessment of residents was done using the
      "standardized American Board of Internal Medicine Mini-CEX evaluation form."
      Feedback about the Mini-CEX was taken from the residents and faculty on separate
      questionnaires consisting of close- and open-ended questions. A total of 87 Mini
      CEX encounters were done with 13 faculty and 29 residents over 6-month study
      period. Results: Residents perceived that it is a method that does the assessment
      of skills, prerequisite for good clinical performance with provision of immediate
      feedback. Most of the residents felt that it improved their clinical skills,
      uplifted the personal development, and impart a better one to one student-teacher
      interaction. Almost all the faculty were satisfied with this method of
      assessment. They found it useful for improved learning of themselves also. Both
      residents and faculty suggested to incorporate Mini-CEX in curriculum.
      Conclusions: Mini-CEX is an acceptable learning tool as reflected by the
      residents and faculty. It is feasible to use mini-CEX for assessment of
      residents.

PMID- 29344453
TI  - Introduction of Medical Humanities in MBBS 1st Year.
AB  - Context: Most vital areas of patient management such as empathy, professionalism,
      and ethics are lacking in fresh undergraduates. These areas are considered to be
      part of hidden curriculum, and as these are not formally taught, we lack
      competent medical graduates. Introduction of medical humanities (MH) early in the
      medical curriculum can help to inculcate required soft skills. Aims: This study
      aims to develop, administer, and evaluate MH module in 1st year MBBS students.
      Settings and Design: Module of MH was introduced among 150 1st year MBBS medical
      students. Subjects and Methods: After taking permission from ethical committee of
      the institute, a core committee for development of MH module was formed. A
      standardized validated module for MH comprising of three sessions was formed and
      was introduced in 1st year MBBS 150 students. Evaluation was done in the form of
      student and faculty feedback questionnaire, consisting of open- and closed-ended
      questions. Statistical Analysis Used: Analysis was done using descriptive
      statistics using mean and standard deviation. Results: According to participants'
      feedback and perception, mean overall rating of MH module was 4.69, indicating
      that it was received well by the students. Out of 3 sessions conducted, students
      gave maximum grades to session 2: cinemeducation. Results of faculty feedback
      questionnaire indicated that MH is needed and should be introduced in every batch
      of 1st year MBBS and should be continued longitudinally. Conclusions: Awareness,
      knowledge, and attitude of students improved as a result of MH module. Our
      results indicate that such modules should be implemented in undergraduate medical
      curriculum.

PMID- 29344454
TI  - Critical Review of "Family Health Advisory Services" Assessment in MBBS Training
      Program in Community Medicine.
AB  - Context: Family Health Advisory Services (FHAS) posting as well as its assessment
      is resource demanding but fails to enjoy priority. Study focuses on a holistic
      overview of the assessment process to understand need for change. Aims: The aim
      of this study is to identify perceived gaps in current assessment practices
      related to FHAS posting. Settings and Design: A cross-sectional mixed method
      study among all the V semester students currently undergoing assessment for the
      posting, past students (selected VII semester students and interns), preceptors
      (supervising residents - postgraduate students in department and senior resident,
      health assistants, medical social service officer), and involved faculty. Subject
      and Methods: Self-administered questionnaire, in-depth interview, focus group
      discussions (two) as well as observations using checklist were used for data
      collection and triangulation. Statistical Analysis Used: Quantitative data used
      in this study were statistical measures of central tendency and dispersion.
      Qualitative data transcript repeatedly read to identify underlying common themes,
      compared to draw inference. Results: There was a lack of guidelines and
      communication regarding assessment. Formative assessment was not performed and
      replaced by one time end assessment. All components of learning were not
      assessed. End-posting assessment was not standardized and unrelated to learning
      objectives. Award of scores was skewed toward right for intervention and toward
      left for analysis and community diagnosis. Conclusions: There is a need to focus
      on proper implementation of programme to strengthen formative assessment.
      Assessment should be relevant to learning objectives of posting. Faculty has to
      lead by example.

PMID- 29344455
TI  - Qualitative Assessment of Learning Strategies among Medical Students Using Focus
      Group Discussions and In-depth Interviews.
AB  - Background: Globally, students with top academic performance and high
      intellectual capacity usually opt to study medicine. However, once students get
      enrolled, their academic performance varies widely. Such variations appear to be
      determined by various factors, one of them being types of learning strategies
      adopted by students. The learning strategies utilized by the students with better
      academic performance are likely to be more effective learning strategies. Aims
      and Objectives: The objective is to identify effective learning strategies used
      by medical students. Methodology: This study was carried out among the MBBS
      students of Final Professional Part I. Students were categorized into three
      groups namely: high, average, and low rankers based on overall academic
      performance in second Professional University examination. First, a questionnaire
      consisting of closed- and open-ended questions was administered to students, to
      find their learning strategies. Subsequently, focus group discussion and in-depth
      interviews were conducted for high- and low-rankers. Discussions were audio
      recorded, transcribed, and analyzed. Key statements were highlighted, collated,
      and categorized into general themes and sub-themes. Results: Evident themes which
      emerged as effective strategies were hard work in the form of regularity of
      studies, meticulous preparation of notes, constructive use of time, utilization
      of e-learning, learning styles and deep learning approach and regular ward
      visits. Intrinsic motivation, family support, balancing physical activities and
      studies, guidance by seniors, teachers, dealing with nonacademic issues such as
      language barriers and stress were also identified as important strategies.
      Conclusions: Disseminating effective learning strategies in a systematic manner
      may be helpful to students in achieving better academic outcomes. Furthermore,
      educationists need to modulate their teaching strategies based on students'
      feedback.

PMID- 29344456
TI  - Early Clinical Exposure as a Learning Tool to Teach Neuroanatomy for First Year
      MBBS Students.
AB  - Context: Early clinical exposure (ECE) is one of the important tools to teach
      basic science to the MBBS students. It is one form of vertical integration
      between basic science and clinical subjects. This study is an effort at exploring
      the use of ECE as a motivational tool toward better learning in neuroanatomy for
      first year MBBS students. Aim: This study aims to make the students interested
      and motivated to study neuroanatomy by using ECE as learning tool in neuroanatomy
      and to make the students enable to retain the knowledge of neuroanatomy more
      efficiently and correlate the knowledge of neuroanatomy with neuromedicine.
      Settings and Design: This study was conducted in collaboration with the
      Departments of Anatomy, General Medicine and Medical Education Unit in the year
      2016. This was cross-sectional study. Subjects and Methods: One hundred and fifty
      students of 1st Professional MBBS were subdivided into two groups. After
      preliminary classes on brain, brainstem, and spinal cord for both groups,
      conventional lecture classes were taken for Group A only on upper motor neuron
      (UMN) and lower motor neuron (LMN) paralysis, and only Group B visited General
      Medicine ward where HOD, General Medicine showed and examined patients of UMN
      paralysis and LMN paralysis, elicited different symptoms, and discussed different
      investigation. It was followed by assessment of all by problem-based multiple
      choice questions (MCQ) and short answer questions. Then, Group B attended lecture
      class on different cranial nerve palsy whereas Group A visited medicine ward. It
      was followed by assessment of both groups by problem-based MCQ and short answer
      questions. The performance was compared. Then, the feedback of the students on
      ECE was collected by means of reflection writing followed by administration of
      questionnaire. Then, the perception of teachers regarding ECE was recorded by
      focused group discussion. Statistical Analysis Used: Student's t-test was used to
      compare the performance of both batches. Reflection writing and focus group
      discussion were analyzed qualitatively. Results: There was a significant
      difference in Group A (P = 0.019) but no significant difference in Group B (P =
      0.679). All the teachers opined that ECE was an efficient method but more time
      and interdepartmental collaboration were necessary. Conclusions: Group A improved
      performance due to ECE but Group B maintained the motivational effect of it.
      Therefore, ECE can be used as an effective learning tool.

PMID- 29344457
TI  - Development and Implementation of Module for Medical Graduates to Improve Socio
      cultural Sensitivity towards People Living with HIV.
AB  - Background: Health professionals are documented as an important cause for
      stigmatizing people living with HIV (PLHIV). Since traditional teaching on HIV in
      India does not address cultural competencies, medical graduates lack
      sociocultural sensitiveness while addressing the health needs of PLHIV. Aim: The
      aim of this study is to develop and to implement a module for medical graduates
      to improve their sociocultural sensitivity toward PLHIV. Methodology: A module
      was designed and introduced to address the core sensitive issues in HIV among
      medical graduates with the help of trained faculty. It included community
      education sessions including interaction with PLHIV to address cross-cultural
      issues and understand their health needs. Feedback for the perception of faculty
      and students was obtained. Knowledge and skills improvement was assessed through
      pre- and post test and direct observation of procedural skills (DOPS). Results:
      Mean feedback score was high for all the components covered by the module. It was
      found to be more for "usefulness of module" (4.91 +/- 0.27836 on a scale of 5)
      than other components of the module. Feedback by faculty showed almost perfect
      agreement on "improvement of student's clinical skills" and "bringing perfection
      in their future practice" across multiple raters. Multiple response open-ended
      feedback showed, 78 (19%) responses affirmed improvement in communication skills
      with training in this module. Pre- and post test mean score for knowledge showed
      an increase (22.1 to 26.49). Mean skills improvement as per expectations were
      86.81 and beyond expectations were 5.34. Conclusions: Training the medical
      graduates in structured HIV specific module improves their socio-cultural
      sensitivity toward PLHIV and is perceived useful.

PMID- 29344458
TI  - Case-based Learning in Microbiology: Observations from a North West Indian
      Medical College.
AB  - Background: Microbiology is usually taught by conventional lectures, and its
      retention and application is observed to be poor among medical
      graduates/practitioners. Aim and Objectives: Introduction of case-based learning
      (CBL) in microbiology for second-year professional MBBS students. Materials and
      Methods: Students were divided into two groups of fifty each. Four clinical cases
      were used for CBL. One group had two CBL sessions whereas the other had didactic
      lectures (DLs) and then the groups were crossed over. Case scenario handouts were
      given to students a week before the session, and smaller groups were formed for
      discussions and presentations in CBL sessions. Posttest, in multiple choice
      questions format, was conducted in two phases: First, immediately after the
      completion of the four CBL and DL sessions, and second, 6 weeks after the first
      posttest. Student and faculty feedback was taken about CBL sessions. Results:
      Hundred MBBS students of the fourth semester voluntarily participated in the CBL
      study. The CBL scores were significantly higher than DL session scores (P =
      0.015). This difference was more marked in scoring done after 6 weeks of session
      completion (P < 0.001). Student reported satisfaction in being taught by CBL
      method in 5-point Likert scale feedback form. Faculty feedback was positive for
      CBL. Conclusions: CBL helped in retention of knowledge and its application better
      than DL in our observation. More sessions on commonly encountered case scenarios
      will be useful for students in recalling basic science knowledge in their later
      years as practitioners.

PMID- 29344459
TI  - Module for Interns in Medical Ethics: A Developmental Diegesis.
AB  - Background: Media report is rife with incidences of doctor-patients' conflict,
      and this partly is due to communication gap and unethical practices being adopted
      by the doctors. Our regular curriculum fails to impart any training in ethical
      issues in patient care. Imparting training to students in these soft-skills is
      the need of the hour. Aim and Objectives: To develop a module for interns in
      medical ethics (MIME) in patient care, validate it and pilot run the module for
      standardization. Methodology: After conducting faculty development workshop in
      curriculum designing and three rounds of Delphi with alumni, a module in medical
      ethics was developed and peer validated. The questionnaire for pilot run,
      questionnaire for future use of module delivery and pre- and post-test were also
      peer validated. The module was delivered to 17 interns as pilot run in the form
      of 4 days' workshop. After pilot run, the module was standardized to 10 broad
      topics and 3 days' workshop. The questionnaire for future delivery of module in
      regular routine was also validated during pilot run. Results: Twenty-five faculty
      members participated in 1 day faculty development workshop and 59 alumni
      completed three rounds of Delphi. After peer review by five experts, a module of
      11 broad areas was developed and was pilot run on 17 interns. Based on the
      feedback from pilot run, a standardized, validated 18 h teaching MIME in patient
      care was developed. Conclusion: Pilot study proves that curriculum innovation in
      the form of medical ethics training to interns; when as undergraduate students,
      they actively participate in patient care under supervision will go a long way in
      inculcating soft skills like ethics, compassion and communication in them.

PMID- 29344460
TI  - Impact of Integrated Teaching Sessions for Comprehensive Learning and Rational
      Pharmacotherapeutics for Medical Undergraduates.
AB  - Background: It is postulated that integrated teaching method may enhance
      retention of the knowledge and clinical applicability of the basic sciences as
      compared to the didactic method. Aim: The present study was undertaken to compare
      the integrated teaching method with the didactic method for the learning ability
      and clinical applicability of the basic sciences. Materials and Methods: The 2nd
      year MBBS students were divided into two groups randomly. The study was conducted
      into two stages. In the first stage, conventional didactic lectures on
      hypertension (HT) were delivered to one group and multidisciplinary integrated
      teaching to another group. For the second stage, diabetes mellitus groups were
      swapped. Retention of the knowledge between the groups were assessed through a
      multiple choice questions (MCQ) test. Feedback of the students and faculty was
      obtained on a 5 point Likert scale. For the comparison, student's data were
      regrouped into four groups, i.e., integrated HT, didactic HT, integrated diabetes
      and didactic diabetes. Results: There was no significant difference of MCQ score
      between integrated HT, didactic HT, and integrated diabetes group. However, the
      score obtained in didactic diabetes was significantly more (P = 0.00) than other
      groups. Majority of the students favored integrated teaching for clinical
      application of basic science and learning of the skill for the future clinical
      practice. Faculties considered integrated method as a useful method and suggested
      frequent use of this method. Conclusion: There was no clear difference in
      knowledge acquisition; however, the students and faculties favored integrated
      teaching method in the feedback questionnaire.

PMID- 29344461
TI  - Using Role-plays as an Empathy Education Tool for Ophthalmology Postgraduate.
AB  - Purpose: To assess the role of an "empathy sensitizing module" (ESM) in
      ophthalmology postgraduates in promoting effective empathetic communication.
      Methodology: Thirty-nine ophthalmology postgraduates were taught effective
      empathetic communication using specially designed module, comprising of five
      illustrative role-plays. We evaluated the impact of the training by (a) self
      assessment of empathy quotient by residents using Jefferson Scale of Empathy (JSE
      scale) before and 6 weeks after ESM training and (b) nonparticipant observation
      (NPO) by trained faculty in real-life settings over the next 4 months. A peer
      validated, self-designed checklist was used for NPO. The change in score was
      analyzed using Student's paired t-test. The faculty observed the use of empathy
      in real-life patient encounters of the trainees over the next 6 months. In
      addition, secondary qualitative data were collected and analyzed to assess the
      impact of the module on other stakeholders such as the role-playing undergraduate
      students and core faculty. Results: Pretraining assessment revealed that concept
      of empathy during patient communication was understood by only 10% students.
      PostESM training, the self-rated mean empathy score, on JSE, significantly
      increased from 95.9 to 106.7 (of a maximum of 140). This was also confirmed by a
      significant improvement in externally rated empathy and soft skills scores (from
      29.3 to 39.1; of a maximum of 55) using the NPO tool. Focus group discussion was
      done on the continued display of empathy by the trainees in real-life situation
      over 6 months of observation by the faculty. The group agreed that there was a
      gradual attrition of initial gain in empathy behavior over the observation period
      of 6 months. The spillover benefits of the training process were observed among
      the role-playing undergraduates as well. A thematic analysis of their reflections
      on the process revealed a substantial change with an improved understanding of
      effective communication. Conclusions: There is a definite scope for introducing
      empathetic communication in medical training. Empathetic communication can be
      improved by effective training in a contextual manner with a need for regular
      reinforcement. Sensitization at all levels including the faculty is required to
      implement effective communication skills in medical profession.

PMID- 29344462
TI  - Introducing Mentoring to 1st-year Medical Students of a Private Medical College
      in North India: A Pilot Study.
AB  - Background: The stress of complex medical course, emotional immaturity, and
      adaptations to new surroundings are the challenges faced by the new medical
      entrants. Therefore, mentorship program was introduced to support them for their
      academic and personal development. Aim and Objectives: The aim of this study is
      to introduce and to assess the perception of mentors and mentees on mentorship
      program. Materials and Methods: A mentorship program was designed for Bachelor of
      Medicine and Bachelor of Surgery (MBBS) First Professional students. A 1-day
      workshop was conducted to sensitize the faculty. Seventeen faculty members from
      various departments volunteered to be mentors. After sensitization, 150 MBBS
      First Professional students were divided among these faculty members by lottery
      system. A regular visit of mentees was scheduled with the mentor. At the end of
      mentorship program, the perception of mentors and mentees was taken using a
      validated and semi-structured feedback questionnaire. A focus group discussion of
      students was also conducted. Results: A total of 112 students and 16 faculty
      members completed the feedback questionnaire. The mentors considered this program
      helpful in their self-improvement, teaching, and communication skills. Most of
      the mentees felt that this program helped them emotionally and academically. It
      was a good way to develop a strong student-teacher relationship. All the mentors
      and mentees were satisfied with the mentorship program. Conclusions: The newly
      introduced mentorship program helped in the overall development of mentors and
      mentees. Both mentors and mentees were extremely satisfied with this program and
      considered this as a successful intervention.

PMID- 29344463
TI  - Team-based Learning Strategy in Biochemistry: Perceptions and Attitudes of
      Faculty and 1st-Year Medical Students.
AB  - Background: Team-based learning (TBL) strategy has been widely adapted by medical
      schools all over the world, but the reports regarding the perceptions and the
      attitudes of faculty and undergraduate medical students towards TBL approach have
      been conflicting. Aim: The study aimed to introduce TBL strategy in curriculum of
      Biochemistry after evaluating its effectiveness through perceptions and attitudes
      of faculty and 1st-year medical students. Materials and Methods: One hundred and
      fifty students of first professional M.B.B.S and five faculty members
      participated in the study. Their responses regarding perceptions and attitudes
      towards TBL strategy were collected using structured questionnaires, focus group
      discussions, and in-depth interviews. Data were analyzed using Wilcoxon signed
      rank test, paired sample t-test, and Mann-Whitney U-test. Results: Majority of
      the students expressed satisfaction with team approach and reported improvement
      in the academic scores, learning styles, and development of problem-solving,
      interpersonal, and professional skills. The faculty, however, recommended a
      modified TBL approach to benefit all sections of the students for the overall
      success of this intervention. Conclusion: TBL is an effective technique to enable
      the students to master the core concepts and develop professional and critical
      thinking skills; however, for the 1st-year medical students, a modified TBL
      approach might be more appropriate for the effective outcomes.

PMID- 29344464
TI  - Cannabinoids in the Treatment of Epilepsy: Hard Evidence at Last?
AB  - The interest in cannabis-based products for the treatment of refractory epilepsy
      has skyrocketed in recent years. Marijuana and other cannabis products with high
      content in Delta(9) - tetrahydrocannabinol (THC), utilized primarily for
      recreational purposes, are generally unsuitable for this indication, primarily
      because THC is associated with many undesired effects. Compared with THC,
      cannabidiol (CBD) shows a better defined anticonvulsant profile in animal models
      and is largely devoid of adverse psychoactive effects and abuse liability. Over
      the years, this has led to an increasing use of CBD-enriched extracts in seizure
      disorders, particularly in children. Although improvement in seizure control and
      other benefits on sleep and behavior have been often reported, interpretation of
      the data is made difficult by the uncontrolled nature of these observations.
      Evidence concerning the potential anti-seizure efficacy of cannabinoids reached a
      turning point in the last 12 months, with the completion of three high-quality
      placebo-controlled adjunctive-therapy trials of a purified CBD product in
      patients with Dravet syndrome and Lennox-Gastaut syndrome. In these studies, CBD
      was found to be superior to placebo in reducing the frequency of convulsive
      (tonic-clonic, tonic, clonic, and atonic) seizures in patients with Dravet
      syndrome, and the frequency of drop seizures in patients with Lennox-Gastaut
      syndrome. For the first time, there is now class 1 evidence that adjunctive use
      of CBD improves seizure control in patients with specific epilepsy syndromes.
      Based on currently available information, however, it is unclear whether the
      improved seizure control described in these trials was related to a direct action
      of CBD, or was mediated by drug interactions with concomitant medications,
      particularly a marked increased in plasma levels of N-desmethylclobazam, the
      active metabolite of clobazam. Clarification of the relative contribution of CBD
      to improved seizure outcome requires re-assessment of trial data for the subgroup
      of patients not comedicated with clobazam, or the conduction of further studies
      controlling for the confounding effect of this interaction.

PMID- 29344466
TI  - Comparison of Autonomic Function before and after Surgical Intervention in
      Patients with Temporal Lobe Epilepsy.
AB  - Background and Purpose: Refractory temporal lobe epilepsy (TLE) is commonly
      associated with imbalances in cardiovascular (CV) parasympathetic and sympathetic
      functions, which are treated using TLE surgery. We investigated the effect of
      hemispheric lateralization of seizure foci on autonomic CV functions before and
      after TLE surgery. Methods: The study was conducted on patients with left TLE
      (LTLE, n = 23) and right TLE (RTLE, n = 30) undergoing unilateral TLE surgery. To
      assess the autonomic CV functions, changes in the heart rate (DeltaHR) and blood
      pressure (BP) were measured using a standardized battery of autonomic reactivity
      tests before surgery and at 3 and 6 months after surgery. Results: Before
      surgery, DeltaHR and the expiration to inspiration ratio (E:I) during the deep
      breathing test were higher in the LTLE group than in the RTLE group (both p <
      0.001), but both outcomes were comparable between the groups at 3 and 6 months.
      DeltaHR decreased at 3 and 6 months (p < 0.001 and 0.01, respectively) compared
      with preoperative values. The E:I at 3 months in the LTLE group was lower (p =
      0.04) than the preoperative values. Decrease in systolic BP during the head-up
      tilt test was greater in the LTLE group than in the RTLE group (p = 0.002) before
      surgery. The maximum increase in diastolic BP during the cold pressor test was
      lower in the RTLE group at 6 months than that before surgery (p = 0.001) and in
      the LTLE group (p = 0.002). Conclusions: We found that hemispheric lateralization
      of seizure foci in the temporal lobe had a differential effect on autonomic CV
      functions before surgery. Before surgery, parasympathetic reactivity was higher
      in the LTLE group, and sympathetic reactivity was higher in the RTLE group. After
      surgery, autonomic CV functions were comparable between the groups, suggesting
      that TLE surgery stabilizes autonomic CV functions.

PMID- 29344465
TI  - Grey and White Matter Alterations in Juvenile Myoclonic Epilepsy: A Comprehensive
      Review.
AB  - Juvenile myoclonic epilepsy (JME) has been classified as a syndrome of idiopathic
      generalized epilepsy and is characterized by a strong genetic basis, age-specific
      onset of seizures, specific types of seizures, generalized spike-wave discharges
      on electroencephalography, and a lack of focal abnormality on magnetic resonance
      imaging (MRI). Recently, a wide range of advanced neuroimaging techniques have
      been utilized to elucidate the neuroanatomical substrates and pathophysiological
      mechanisms underlying JME. Specifically, a number of quantitative MRI studies
      have reported focal or regional abnormalities of the subcortical and cortical
      grey matter, particularly the thalamus and frontal cortex, in JME patients. In
      addition, diffusion tensor imaging studies have pointed to disrupted
      microstructural integrity of the corpus callosum and multiple frontal white
      matter tracts as well as thalamofrontal dysconnectivity in JME patients.
      Converging evidence from neuroimaging studies strongly suggests that JME is a
      predominantly thalamofrontal network epilepsy, challenging the traditional
      concept of JME as a generalized epilepsy. There is also limited evidence
      indicating extrafrontal and extrathalamic involvement in JME. This systematic
      review outlines the main findings from currently available MRI studies focusing
      on grey and white matter alterations, and discusses their contributions to the
      etiology and pathophysiology of JME. The clinical utility, advantages, and
      drawbacks of each imaging modality are briefly described as well.

PMID- 29344467
TI  - Longitudinal Change in Thyroid Hormone Levels in Children with Epilepsy on a
      Ketogenic Diet: Prevalence and Risk Factors.
AB  - Background and Purpose: The aim of this study is to evaluate the prevalence of
      hypothyroidism and the change of thyroid hormone level in the children with
      epilepsy on a ketogenic diet (KD). Methods: The levels of serum free thyroxine
      (fT4) and thyroid-stimulation hormone (TSH) were measured at the start of the KD
      and at 6- to 12-month intervals in children with intractable epilepsy.
      Hypothyroidism was defined as fT4 level < 0.8 ng/dL and TSH level > 6.0 MUIU/mL.
      Results: A total of 28 children (17 boys and 11 girls) were enrolled in the
      study. The mean age of onset of seizure was 1.4 +/- 1.6 years, the mean age of
      the start of the KD was 3.2 +/- 2.4 years, and the mean duration of KD was 1.9 +/
      1.5 years. Overall, there was no significant longitudinal change in the mean fT4
      (0.99 +/- 0.25 vs. 0.94 +/- 0.71 ng/dL, p = 0.28) and TSH (2.94 +/- 1.32 vs. 3.18
      +/- 1.21 MUIU/mL, p = 0.44) levels from the start of the KD to last follow-up.
      The patients with a younger age of seizure onset, earlier initiation of KD, and
      higher serum levels of cholesterol and triglyceride had a significant decrease in
      fT4 levels and increase in TSH levels during the KD. Sex, duration of the seizure
      or KD therapy, seizure types, seizure frequency, seizure outcomes, brain lesion,
      ratio of KD, and being overweight did not affect the longitudinal change of fT4
      and TSH levels during KD. Conclusion: Thyroid function had no significant
      longitudinal decrease in pediatric epilepsy during KD therapy. However, careful
      monitoring of the serum levels of fT4/TSH should be recommended in children on
      KDs, especially in those with earlier seizure onset, earlier start of KD, and
      higher levels of lipid profiles.

PMID- 29344468
TI  - Levetiracetam-Induced Skin Hyperpigmentation: An Extremely Rare Undesirable Side
      Effect.
AB  - Levetiracetam is one of the newer second-generation antiepileptic drugs with
      multiple mechanisms of action. Cutaneous side effects due to levetiracetam are
      rarely reported in the literature. In this article, we describe a patient with
      skin hyperpigmentation due to the treatment with levetiracetam with complete
      resolution after discontinuation of the medication. In addition, we review the
      topic and hypothesize the mechanism behind this rare complication. To the best of
      our knowledge, this is the first report of skin hyperpigmentation as a side
      effect of levetiracetam in the literature. The prescribing physicians should
      inform the patients about all potential side effect of levetiracetam including
      skin hyperpigmentation. Similar to many undiagnosed conditions, increased
      awareness of their existence is the key to diagnosis. Early recognition and
      timely cessation of therapy are important to reverse this effect. Further studies
      should be conducted to explore the pathophysiology of this rare side effect.

PMID- 29344469
TI  - Successful Use of Therapeutic Hypothermia for Refractory Nonconvulsive Status
      Epilepticus.
AB  - Therapeutic hypothermia (TH) has rarely been utilized as an adjunct to
      anticonvulsants in treating patients with refractory convulsive status
      epilepticus (CSE). However, determining the effectiveness of TH in CSE is
      difficult due to the unavoidable use of sedative drugs to manage hypothermia.
      Additionally, the effectiveness of TH has not been studied in patients with
      refractory non-convulsive status epilepticus (NCSE). Here, we report the
      successful use of TH without additional sedative drugs in a patient with temporal
      lobe epilepsy and refractory NCSE. A 46-year-old man was referred to the
      neurology department because of recurrent seizure attacks. Electroencephalography
      (EEG) after first-line status treatment showed continuous periodic discharges
      consistent with NCSE. He was started simultaneously on continuous EEG monitoring
      and TH, but was not administered any benzodiazepines to control shivering or
      maintain TH. During TH, EEG abnormalities gradually improved, and the patient
      regained consciousness in accordance with the improvement in EEG. The patient was
      alert and his EEG had normalized a few days after starting TH. To the best of our
      knowledge, this is the first report describing the successful treatment of
      refractory NCSE with TH. As no sedative drugs were used during the maintenance of
      hypothermia, NCSE control may have been achieved by TH alone.

PMID- 29344470
TI  - Aphasic Status Epilepticus Associated with Uremia.
AB  - Aphasic status epilepticus (ASE) is a rare disorder characterized by recurrent
      aphasia without impairment of other cognitive functions. A 76-year-old woman with
      chronic kidney disease developed ASE after neglecting peritoneal dialysis.
      Magnetic resonance imaging failed to demonstrate an appropriate lesion.
      Electroencephalography demonstrated ictal discharges in the left frontotemporal
      leads. ASE disappeared after intravenous valproic acid and correction of uremia.
      This is the first case report of ASE in a patient with acute aggravation of
      uremia.

PMID- 29344471
TI  - A 6-Month-Old Girl with Incontinentia Pigmenti Presenting as Status Epilepticus.
AB  - Incontinentia pigmenti (IP) is an uncommon neurocutaneous syndrome. Its initial
      diagnosis is based primarily on characteristic papulovesicular skin lesions and
      early-onset neonatal seizures. In contrast to typical early neurologic
      manifestations, we encountered a normally developed 6-month-old female patient
      with hyperpigmented whorls on her body. Following respiratory syncytial virus
      infection and fever, the patient exhibited status epilepticus. Brain magnetic
      resonance imaging studies of the patient were compatible with the findings of
      acute encephalopathy in IP. Genetic analysis showed an 11.7 kb deletion within
      the gene encoding inhibitor of kappa-B kinase gamma. The patient was treated with
      anticonvulsants and subsequently reached expected developmental milestones after
      discharge. These findings indicate that when a patient presents with status
      epilepticus, meticulous examination for skin lesions should be performed to
      determine whether the patient has a neurocutaneous syndrome, such as IP.

PMID- 29344472
TI  - Status Epilepticus as an Unusual Manifestation of Heat Stroke.
AB  - Heat stroke (HS) is a medical emergency and life threatening condition,
      characterized by body temperature over 40 degrees C. This can lead to dysfunction
      of multiple organs such as the heart, liver, kidneys, lungs, blood coagulation
      system, and central nervous system. Neurological complications include change in
      consciousness, cerebellar dysfunction, convulsions, aphasia, muscular weakness,
      and parkinsonism. Cerebellar syndrome is the most common neurological finding in
      HS. We report a case of HS presenting with status epilepticus, without any other
      neurological manifestations. A 42 year old man, previously diagnosed with bipolar
      disorder, was admitted to the emergency room with high fever and repetitive
      generalized tonic-clonic seizures. He had been found unconscious after 4 hours of
      heavy physical work under extremely hot weather conditions. He was diagnosed with
      HS accompanied by status epilepticus, and treated with emergency body cooling and
      antiepileptics. Five days after admission, he regained consciousness and the
      laboratory parameters that were initially abnormal returned to normal values. On
      day 14, he was discharged without any neurological complications.

PMID- 29344473
TI  - Intractable Epilepsy with Solitary Cerebral Calcification.
AB  - Cerebral calcification is a common incidental finding upon brain imaging and its
      epileptogenicity is often underestimated. Here, we report a case of intractable
      epilepsy arising in conjunction with a solitary cerebral calcification. A 42-year
      old male with intractable epilepsy was admitted to the epilepsy clinic for
      invasive epilepsy surgery. Brain magnetic resonance imaging revealed a slight
      high-intensity signal change in the right amygdala and a small, calcified lesion
      in the right lateral temporal region. The patient underwent invasive monitoring
      with subdural electrodes. He had five habitual seizures with automatisms and fast
      activity. These seizures initiated in the right lateral temporal area just above
      the solitary calcified lesion. Neuropathology of the calcified lesion showed no
      specific findings apart from a fibrocalcific nodule. Thus, although solitary
      cerebral calcifications may be an asymptomatic or coincidental finding in some
      patients, they may also have a highly epileptogenic focus.

PMID- 29344474
TI  - Corneal Myofibroma (Keloid) in a Young Patient with Neurofibromatosis Type 2.
AB  - We present a 27-year-old male patient with neurofibromatosis type 2 (NF2), facial
      palsy, and lagophthalmos following acoustic neuroma removal and an impressing
      vascularized corneal tumor, which was excised. Histology showed a fibrous tumor
      with small vessels, and immunohistochemistry was positive for vimentin and
      negative for smooth muscle actin, S100, and GFAP. We assume a corneal myofibroma
      (keloid), which in this case rather represents a reactive lesion. This entity has
      not been described before in NF2 or in facial palsy-associated lagophthalmos in
      general.

PMID- 29344475
TI  - Ring-Shaped Leiomyoma of the Ciliary Body.
AB  - Purpose: Ciliary body mesectodermal leiomyoma is a rare, benign smooth muscle
      tumor that typically presents in women in the second to fourth decade of life.
      The diagnosis is typically based on clinical color, funduscopic appearance,
      transillumination properties, and B-scan ultrasonography. Methods: We present a
      patient with a 360 degrees  ciliary body mass with transillumination and
      ultrasonographic properties consistent with a ring melanoma. Results: This case
      emphasizes the difficulty in differentiating the benign leiomyoma from similar
      appearing malignant tumors such as melanoma. Conclusion: The eye was enucleated
      and the diagnosis was ring-shaped leiomyoma.

PMID- 29344476
TI  - Acute Angle Closure Precipitated by Hemorrhage and Necrosis of a Large Uveal
      Melanoma in the Setting of Systemic Immunomodulatory Therapy.
AB  - Management of nonmetastatic uveal melanoma has been well studied and a large body
      of work has been published by the Collaborative Ocular Melanoma Study (amongst
      many others). Management of uveal melanoma that is found to be metastatic upon
      initial diagnosis, however, is less well defined. We report an interesting case
      of acute angle closure caused by necrosis and hemorrhage into a large uveal
      melanoma occurring shortly after initiation of immunomodulatory therapy with
      ipilimumab and nivolumab for metastatic disease. The use of these
      immunomodulatory agents in the setting of metastatic uveal melanoma is not well
      studied, and our case illustrates the importance of interdisciplinary
      communication in order to best decide the timing of surgical and systemic medical
      management to optimize outcomes and minimize morbidity.

PMID- 29344477
TI  - Is There an Increased Prevalence of Asteroid Hyalosis in Eyes with Uveal
      Melanoma? A Histopathologic Study.
AB  - During the planning meeting for the Collaborative Ocular Melanoma Study (COMS)
      prior to the start of patient recruitment in 1986, there was an interest
      expressed in determining whether a relationship existed between the presence of
      uveal melanoma (UM) and asteroid hyalosis (AH). To answer this question, the
      ophthalmic examination form (unlike the pathology form for enucleated eyes) for
      each COMS patient asked whether AH was present or not. Though an increased
      prevalence was not found, this result was never published. A recent unpublished
      study at the University of Wisconsin School of Veterinary Medicine indicated a
      higher prevalence of AH in canine eyes with UM when compared to control eyes
      (without tumor) enucleated for goniodysgenesis. This further increased our
      interest in revisiting the published literature, clinical records, and
      histopathology slides of the enucleated eyes from the COMS study, as well as the
      histopathology slides on file in the University of Wisconsin Eye Pathology
      Laboratory. While cases with both AH and UM were occasionally encountered in the
      literature, clinically, we could not find a previous study focusing on these two
      processes. This study was conducted to explore whether such an association
      exists.

PMID- 29344478
TI  - Incidentally Discovered Adenoid Cystic Carcinoma of the Lacrimal Gland with
      Isolated Liver Metastases.
AB  - Aim: To report a rare presentation of adenoid cystic carcinoma (ACC) of the
      lacrimal gland. Method: This is a case report presenting clinical, radiographic,
      and histopathologic findings. Results: A 72-year-old female with no reported
      ocular symptoms was found to have an incidental right orbital mass on imaging.
      Additional studies revealed multiple liver lesions, which were biopsied and found
      to be consistent with ACC. She was then referred to the ophthalmology service,
      where ocular examination demonstrated 2.5 mm of right proptosis with elevation
      and abduction deficits. Diplopia could be elicited in extreme upgaze and right
      lateral gaze. An excisional biopsy of the orbital mass was performed, with
      histopathology confirming the diagnosis of primary ACC of the lacrimal gland,
      thereby also supporting the initial suspicion that the hepatic ACC lesions
      represented metastases. Conclusion: The authors describe a rare presentation of
      ACC of the lacrimal gland, initially asymptomatic, with metastatic lesions
      restricted to the liver at the time of diagnosis. Three previous cases of ACC
      with isolated metastatic hepatic lesions at the time of diagnosis have been
      reported; all of these cases localized the primary tumor to the salivary glands.

PMID- 29344479
TI  - Mechanisms of Optic Nerve Invasion in Primary Choroidal Melanoma.
AB  - Aim: The aim of this study was to assess morphological risk factors associated
      with optic nerve invasion of choroidal melanoma and to identify possible
      mechanisms of optic nerve invasion. Methods: Medical charts and histology slides
      of patients with primary choroidal melanoma who were treated by
      enucleation/exenteration and whose pathology showed optic nerve invasion were
      reviewed. Results: Twenty-one patients (mean age: 65.67 +/- 14.72 years) with
      primary uveal melanoma arising from the choroid were included in this analysis. A
      peripapillary location was present in 86% of the cases. Four types of optic nerve
      invasion were identified: transvitreal invasion (10%); retinal invasion (23%);
      direct peripapillary invasion (57%); and a combined mechanism (10%). Optic nerve
      invasion was prelaminar in 67%, laminar in 10%, and retrolaminar in 23% of the
      cases. Significantly higher largest basal diameter (p = 0.021) and tumor
      thickness values (p = 0.017) and higher rates of vortex vein (p = 0.022) and
      retinal invasion (p = 0.007) were observed in the transvitreal/retinal invasion
      groups when compared to the direct peripapillary invasion group. Conclusions: A
      peripapillary tumor location was the most common mechanism of optic nerve
      invasion of choroidal melanoma. In 43% of the cases, other mechanisms including
      transvitreal and retinal invasion resulted in optic nerve invasion.

PMID- 29344480
TI  - Primary Conjunctival Tuberculosis Presenting as Dry Eye: A Rare Case Report and
      Review of the Literature.
AB  - Primary conjunctival tuberculosis is very rare in the developed countries. In an
      endemic country like India, it should be considered in the differential diagnosis
      of any unusual conjunctival lesion with unilaterality, chronicity, and
      nonresolution of symptoms after steroid use. We present the case of a 52-year-old
      female who presented with unilateral itching and blurring of vision for 20 days.
      There were irregular nodular elevated areas with shrinkage of the lower palpebral
      conjunctiva. A biopsy of the lesion revealed necrotizing epithelioid cell
      granulomas along with Langhans type of giant cells. However, no acid-fast bacilli
      were seen on Ziehl-Neelsen stain. Systemic examination of the patient was normal,
      and there was no evidence of pulmonary tuberculosis. Polymerase chain reaction of
      conjunctival scrapings was positive for Mycobacterium tuberculosis. The patient
      was started on antitubercular drugs. We present this very rare case of primary
      tuberculosis of the conjunctiva presenting with dryness of the eye.

PMID- 29344481
TI  - Choroidal Melanoma Mimicker: A Case of Metastatic Clear-Cell Renal Cell
      Carcinoma.
AB  - Choroidal melanoma is the most common primary intraocular malignancy, yet
      metastatic disease remains the most common malignancy of the eye. Differentiating
      these entities is essential as treatment, systemic associations, and prognosis
      vary dramatically between the two. Established diagnostic criteria are accurate
      for the diagnosis of uveal melanoma. Yet, metastatic disease may be misdiagnosed
      as a uveal melanoma in rare cases. We report a case of metastatic clear-cell
      renal cell carcinoma masquerading as uveal melanoma. A 73-year-old Caucasian man
      with a history of renal cell carcinoma presented with a 15 * 12 * 7 mm
      homogenous, pigmented, and acoustically hollow mass without hemorrhage or
      exudation. The patient was initially treated with plaque radiotherapy with good
      tumor regression. However, the patient developed pain and vision loss due to
      total exudative retinal detachment. Subsequent enucleation allowed
      histopathologic confirmation of clear-cell renal cell carcinoma. Nine years
      following enucleation, the patient remains in complete remission without evidence
      of other systemic metastases. Renal cell carcinoma should be considered when
      evaluating patients with probable uveal melanoma. Delayed-onset ocular metastasis
      from renal cell carcinoma exhibits an atypical clinical course with the
      possibility of durable remission following enucleation.

PMID- 29344482
TI  - Optic Nerve Obscuration in Retinoblastoma: A Risk Factor for Optic Nerve
      Invasion?
AB  - Background: The objective of this study is to evaluate the risk of optic nerve
      invasion associated with optic nerve obscuration at diagnosis or persisting
      during treatment. Methods: Retrospective review from 2011-2016 of patients with
      advanced retinoblastoma (Group D/E) with complete obscuration of the nerve at
      diagnosis and a second group of patients with persistent, complete obscuration
      throughout treatment. Results: Advanced retinoblastoma was diagnosed in 102 eyes
      of 86 patients. The optic nerve was obscured in 69 eyes (68%) at diagnosis. Of
      these, 30 (43%) underwent salvage therapy and 39 (57%) primary enucleation.
      Histopathologic analysis of primarily enucleated eyes showed 41% prelaminar and
      15% postlaminar invasion. Four eyes in the salvage group demonstrated persistent
      nerve obscuration; 2 were subsequently enucleated without evidence of nerve
      invasion. Average follow-up was 23.5 months (range 1-62 months). Conclusions and
      Relevance: Optic nerve obscuration at diagnosis may be associated with
      postlaminar optic nerve invasion. While persistent, complete obscuration of the
      optic nerve by retinoblastoma during treatment is a poor prognostic sign for both
      globe salvage and vision, it does not appear, in this small cohort, to increase
      the risk of optic nerve invasion. With appropriate control of the intraocular
      tumor, these eyes can be salvaged.

PMID- 29344483
TI  - Retinoinvasive Uveal Melanoma: Report of 2 Cases and Review of the Literature.
AB  - Purpose: To describe the clinical history and histopathologic findings of 2 cases
      of retinoinvasive uveal melanoma. Methods: The medical records and pathology
      specimens of 2 patients with retinoinvasive uveal melanoma were reviewed.
      Results: The first patient had an iris/ciliary body melanoma that was treated and
      the second patient had suspected iridocorneal endothelial syndrome. Both patients
      developed a blind, painful eye; the first patient's right eye was enucleated and
      the left eye of the second patient underwent evisceration. Histopathologic
      examination of the enucleated eye showed a tumor composed of minimally pigmented
      spindle-shaped cells with fusiform nuclei and prominent nucleoli and round cells
      with prominent nucleoli. The tumor cells invaded into the retina where they
      formed perivascular aggregates. Examination of the evisceration specimen showed a
      proliferation of pigmented tumor cells within the stroma of one iris leaflet. The
      tumor cells extended onto the ciliary body and vitreous base and invaded the
      retina. The pathologic diagnosis in both patients was retinoinvasive uveal
      melanoma. Conclusions: Careful funduscopic and imaging examination should be
      performed in eyes with unilateral glaucoma with iris/ciliary body lesions, and
      enucleation, rather than evisceration, should be performed, as retinoinvasive
      melanoma is in the differential diagnosis.

PMID- 29344484
TI  - Adenocarcinoma of the Retinal Pigment Epithelium Arising in Conjunction with Late
      Recurrence and Systemic Metastasis of Retinoblastoma.
AB  - In 1974, an 8-month-old male was diagnosed with bilateral retinoblastoma. His
      left eye was enucleated, while the right eye was salvaged with a combination of
      external beam radiotherapy (4,000 cGy total, divided in 20 fractions) and retinal
      laser treatment. Thirty-nine years later, he developed intraocular recurrence of
      retinoblastoma with extrascleral spread. Histopathological examination also
      identified a second distinct malignancy, retinal pigment epithelium
      adenocarcinoma, arising in continuity with the retinoblastoma. Further
      investigation revealed foci of metastatic retinoblastoma in his parotid gland. He
      was subsequently treated with a combination of orbital exenteration, extensive
      neck dissection, and resection of metastatic foci, followed by a high-dose
      ablative chemotherapeutic regimen consisting of cisplatin, vincristine, and
      cyclophosphamide. Although very rare, late recurrence of retinoblastoma with
      systemic metastasis is possible, and continued clinical observation and
      appropriate long-term follow-up should be considered. Additionally, it is
      important to consider a second primary intraocular tumor in the differential
      diagnosis, especially in a patient with heritable retinoblastoma who has
      undergone radiation therapy.

PMID- 29344485
TI  - Prognostication for Uveal Melanoma: Are Two Tests Better than One?

PMID- 29344486
TI  - Acute Presentation of Mesectodermal Leiomyoma of the Ciliary Body.
AB  - Purpose: We report a case of acutely presenting mesectodermal leiomyoma of the
      ciliary body in a 29-year-old female who reported waking up with swollen eyelids
      of the right eye and light-perception vision. The affected eye had elevated
      intraocular pressure, a flat anterior chamber, and a pale, round mass arising
      from the nasal ciliary body, invading the angle and protruding into the visual
      axis posterior to the lens. Within days, the visual acuity decreased to no light
      perception. The eye was enucleated. Methods: The enucleated eye harbored a tumor
      arising from the ciliary body, measuring 18 mm in the greatest dimension.
      Spindled cells with fibrillary cytoplasmic processes suggested a neural origin
      though negative for S-100, Melan-A, and HMB-45. The cells stained strongly
      positive for smooth muscle actin and vimentin, leading to the diagnosis of
      mesectodermal leiomyoma of the ciliary body. Results: We review the literature to
      expand upon the clinical findings, diagnostic methods, and histopathologic and
      immunohistochemistry characteristics of mesectodermal leiomyoma. Conclusion:
      Leiomyoma must be in the differential diagnosis for ciliary body mass, especially
      in women of reproductive age. Diagnosis relies on histopathology and
      immunohistochemistry. The mechanism of acute symptom onset may be multifactorial.
      This case emphasizes the possibility of acute presentation of a rare, benign
      intraocular tumor.

PMID- 29344487
TI  - Enlarging Pigmented Eyelid Mass Associated with Remote Pencil Trauma.
AB  - The authors present a case of a gradually enlarging pigmented mass of the upper
      eyelid and anterior orbit that was discovered to be the graphite tip of a pencil
      surrounded by macrophages bearing graphite and fibrous tissue. A 25-year-old
      woman with no medical history presented with a gradually enlarging pigmented
      lesion of her left upper eyelid. She denied any history of previous skin cancer,
      trauma, or previous surgery. A biopsy was performed. This revealed an
      encapsulated grayish, pigmented mass within the medial portion of the left upper
      eyelid and anterior orbit. Within the pigmented cocoon, the graphite core of a
      pencil ("pencil lead") was identified. Histopathology demonstrated granulomatous
      inflammation with fibrosis and macrophages.

PMID- 29344488
TI  - Intravitreal Aflibercept as Rescue Therapy for Post-Radiation Cystoid Macular
      Edema Resistant to Intravitreal Bevacizumab: Outcomes at 1 Year.
AB  - Background/Aims: To investigate the efficacy of intravitreal aflibercept as
      rescue therapy for post-radiation cystoid macular edema (CME) resistant to prior
      treatment with intravitreal bevacizumab (IVB). Methods: Retrospective,
      interventional, case-controlled series. Eyes with persistent post-radiation CME
      were treated with intravitreal aflibercept (2 mg/0.05 mL). Central macular
      thickness (CMT) and visual acuity were compared to a matched control group
      treated with only IVB at 1 year. Results: Ten eyes of 10 patients were included,
      with 5 eyes in the intervention and 5 in the control group. The eyes in the
      intervention group had previously been treated with IVB (mean 11.6 injections,
      range 6-22) but failed to show resolution of CME. Following rescue treatment with
      a mean of 9 injections of aflibercept, the mean CMT was reduced from 463 +/- 138
      to 267 +/- 80 MUm (p = 0.02) and the mean Snellen visual acuity was improved from
      20/67 to 20/42 (p = 0.03). At 1 year, the eyes in the intervention group had
      lower CMT (267 +/- 80 vs. 361 +/- 71 MUm, p = 0.09) and significantly better
      Snellen visual acuity (20/48 vs. 20/76, p = 0.02) compared to the control group.
      Conclusions: Aflibercept may be an effective rescue therapy for persistent post
      radiation CME in eyes with incomplete response to IVB, with reduction in CMT and
      improvement in visual acuity.

PMID- 29344489
TI  - Caruncular Oncocytoma Mimicking Malignant Melanoma.
AB  - Purpose: To report a case of pigmented caruncular oncocytoma that simulated
      malignant melanoma and discuss the associated ultrasonographic and pathologic
      features. Method: Case report. Results: An 81-year-old female presented with a
      painless caruncular mass with a smooth brown surface suspicious for melanoma.
      Ultrasound biomicroscopy revealed a round mass with a large central cavity, more
      suggestive of a cystic rather than solid lesion. Following complete surgical
      resection, histopathology revealed a cystadenomatous lesion composed of bland
      cells with copious eosinophilic cytoplasm consistent with oncocytoma that had a
      central blood-filled cavity. Conclusions: Oncocytoma is a benign tumor that can
      appear pigmented clinically and resemble melanoma. The definitive diagnosis
      requires histopathologic evaluation. Oncocytoma should be considered in the
      differential diagnosis of a pigmented caruncular mass.

PMID- 29344490
TI  - Capillary Dropout: A Novel Fluorescein Angiography Finding in Primary
      Vitreoretinal Lymphoma.
AB  - Tissue diagnosis with vitreous and/or retinal biopsy usually confirms the
      diagnosis of primary vitreoretinal lymphoma. Multiple imaging modalities like
      fundus fluorescein angiography, fundus autofluorescence, and optical coherence
      tomography have been used to support the diagnosis of vitreoretinal lymphoma. We
      report a case of a 74-year-old lady diagnosed with primary vitreoretinal lymphoma
      showing a novel fluorescein angiographic finding of capillary dropout. We
      hypothesize that this clinical finding on the fluorescein angiogram may be due to
      the occlusion of the retinal vasculature by the malignant tumor cells. This
      finding also suggests the possible intraocular invasion of the malignant
      lymphomatous cells into the inner retinal layers.

PMID- 29344491
TI  - Hemophagocytic Lymphohistiocytosis in Adults with Intraocular Involvement:
      Clinicopathologic Features of 3 Cases.
AB  - Background/Aims: Hemophagocytic lymphohistiocytosis (HLH) is an infrequent
      inflammatory multisystemic syndrome. Only rare cases with ophthalmic involvement
      describing their pathologic features have been previously reported. Methods: We
      report 3 cases of adult-onset HLH with bilateral ocular involvement and describe
      their clinicopathologic features. Results: Three adult males - 2 with a history
      of viral infection - developed persistent fever, fatigue, bone marrow
      abnormalities, and irreversible multiorgan failure. Visual impairment was also
      documented in 2 cases. Complete autopsies were performed. Ophthalmic pathology
      demonstrated a bilateral histiocytic infiltrate with scant lymphocytes affecting
      the uvea. Focal extension to the retina, optic nerve, and trabecular meshwork
      were also identified, as well as hemophagocytosis in 1 case. Macrophages showed
      strong immunoreactivity for CD163 antibody and lacked BRAF p.V600E mutant
      protein. Conclusion: HLH is an unusual disorder associated with several systemic
      conditions. Histologic features in the eye are poorly documented, with prior
      reports restricted to children. Our 3 adult cases are reported using updated
      criteria and, despite the difference in age, show changes similar to those
      observed in the pediatric population.

PMID- 29344492
TI  - Bilateral Hypopyon Uveitis in Chronic Myeloid Leukemia.
AB  - Background: A leukemic hypopyon is considered an early sign of central nervous
      system involvement or systemic relapse. A differential diagnosis of masquerade
      syndromes should be considered in cases of hypopyon uveitis that are atypical or
      unresponsive to treatment. We report a case of a 45-year-old man who presented
      with bilateral hypopyon uveitis and was subsequently diagnosed as having chronic
      myeloid leukemia. Method: Retrospective case review. Results: A 45-year-old
      diabetic male presented with diminished vision in both eyes for 10 days.
      Ophthalmic evaluation revealed rubeosis iridis, hypopyon, and signs of
      proliferative diabetic retinopathy with panretinal laser photocoagulation scars.
      He subsequently presented 1 week later with a bloodstained hypopyon in his right
      eye and a persistent hypopyon in his left eye. A peripheral blood smear and
      subsequent bone marrow trephine biopsy confirmed the diagnosis of chronic myeloid
      leukemia in blast crisis and he was referred to an oncologist for further
      management. Conclusion: A recalcitrant or atypical hypopyon uveitis can be an
      indicator of a blast crisis or a central nervous system involvement or sign of a
      relapse in cases of leukemia. The presence of unusual bloodstained hypopyon
      helped in identifying the presence of chronic myeloid leukemia and aided in a
      prompt oncology consultation.

PMID- 29344494
TI  - Inhomogeneous Surface Dose Distributions of 106Ru Eye Plaques.

PMID- 29344493
TI  - Comparison of Gene Expression Profiling and Chromosome 3 Analysis by Fluorescent
      in situ Hybridization and Multiplex Ligation Probe Amplification in Fine-Needle
      Aspiration Biopsy Specimens of Uveal Melanoma.
AB  - Purpose: The aim of this paper was to assess the concordance between results of
      DecisionDx-UM specific gene expression profiling (GEP) and fluorescence in situ
      hybridization (FISH) for chromosome 3 analysis, and between DecisionDx-UM GEP and
      multiplex ligation probe amplification (MLPA) in uveal melanoma undergoing
      intraoperative fine-needle aspiration biopsy (FNAB) for metastatic
      prognostication during brachytherapy. Methods: We retrospectively reviewed
      consecutive patients diagnosed with posterior uveal melanoma who underwent
      intraoperative FNAB prior to placement of an iodine-125 radioactive plaque
      between 2012 and 2014. Two cohorts of patients were identified: Cohort 1 - tumors
      in which both GEP and FISH results were obtained, and Cohort 2 - tumors in which
      both GEP and MLPA results were obtained. Results: Forty-four patients were
      identified for Cohort 1. FISH and GEP results were discordant in 7 tumors
      (15.9%). Forty-three patients were identified for Cohort 2. MLPA and GEP were
      discordant in 7 tumors (16.3%). Conclusions: Discordance between GEP and
      chromosome 3 status by FISH and MLPA occurred in our series at a rate of 15.9 and
      16.3%, respectively. Caution must be advised when counseling a patient with a
      good-prognosis GEP "Class 1" result that the uveal tumor may actually harbor
      monosomy 3, which is associated with a poor prognosis for metastasis in nearly
      20% of the patients.

PMID- 29344495
TI  - Retinoblastoma: A Sixteen-Year Review of the Presentation, Treatment, and Outcome
      from a Tertiary Care Institute in Northern India.
AB  - Purpose: To study epidemiology, demographic profile, clinical characteristics,
      and outcome in pediatric patients with retinoblastoma. Methods: This was a
      retrospective review of retinoblastoma patients of a tertiary institute from
      January 1st 1998 to December 31st 2014. Results: The study included 467 patients
      (618 eyes) with a mean age of 34.7 +/- 24.6 months (median = 30; 15 days to 144
      months). Retinoblastoma was bilateral in 151 (32.3%) and there were 61.7% males.
      Intraocular disease was seen in 301 patients (451 eyes [72.9%]) and extraocular
      in 166 patients (167 eyes; 27.0%). Out of the 347 (74.3%) who received treatment,
      primary treatment was chemoreduction in 228 (65.7%) and enucleation in 117
      (33.7%), while 25.6% of patients refused treatment and 151 (43.5%) defaulted
      therapy. Local recurrence was seen in 20 (4.3%), metastasis in 2 (0.4%), and
      deaths in 13 (2.8%) (average follow-up 28.5 +/- 44.4 months). Histopathological
      high risk features were significantly less in the eyes that received
      chemoreduction (5.0%) versus primary enucleation (20.8%) (p < 0.0004), but there
      was no difference in the rate of metastasis, recurrence, and death between the
      two. Conclusions: The majority of retinoblastoma patients in our study had
      advanced disease, and nearly a third had extraocular extension. There were a
      significant number of therapy refusals and dropouts. Chemoreduction led to a
      significant decrease in the histopathological risk factors without affecting the
      outcomes.

PMID- 29344496
TI  - Quadruple Neoplasms following Radiation Therapy for Congenital Bilateral
      Retinoblastoma.
AB  - Purpose: The aim of this study was to describe a 34-year-old male with hereditary
      bilateral retinoblastoma treated with radiotherapy as a child who developed 4
      distinct tumors within the radiation field. Methods: A 34-year-old male with
      bilateral retinoblastoma status postradiation therapy and recurrence requiring
      enucleation presented with left-eye visual acuity changes. Magnetic resonance
      imaging demonstrated a left orbital mass and a right parasellar complex lobulated
      mass (right sphenoid and right cavernous sinus). Two weeks later, the patient
      underwent excision of the orbital mass and biopsy of an upper-lid nodule. This
      was followed by craniotomy for removal of the complex mass. Results: Histology
      revealed 4 distinct tumors, including an undifferentiated pleomorphic sarcoma
      (left orbit), a radiation-induced meningioma (right sphenoid), a schwannoma
      (right cavernous sinus), and a basal-cell carcinoma (left lid). Conclusion:
      Although occurrence of a second neoplasm is a well-known outcome following
      radiation treatment in patients with hereditary retinoblastoma, the diagnosis of
      4 additional neoplasms is rare. Pleomorphic sarcoma, radiation-induced
      meningioma, and schwannoma are uncommon tumors and not well represented in the
      literature describing irradiated retinoblastoma patients. Secondary malignancies
      are a leading cause of early death in retinoblastoma survivors, and long-term
      follow-up is crucial for patient care.

PMID- 29344497
TI  - A Case of Adenocarcinoma of the Retinal Pigment Epithelium: An
      Immunohistochemical and Electron Microscopic Study.
AB  - Purpose: Retinal pigment epithelium (RPE) adenocarcinoma is a very rare malignant
      intraocular tumor. Herein we describe the histopathological features of RPE
      adenocarcinoma. Case: A 36-year-old male was referred to our clinic because of
      floaters in his left eye. The initial diagnosis was malignant melanoma of the
      choroid. We resected the tumor and studied it histopathologically. The tumor
      tissue was investigated by light microscopy including immunohistochemistry using
      antibodies against S-100, HMB-45, EMA, and AE-1. Electron microscopic examination
      was also performed. Results: The tumor arose from the RPE and contained
      intracytoplasmic vacuoles and abundant melanin pigment. There were no nevoid
      cells in the choroid. A small part of the tumor cells showed tubular or lobular
      proliferation and choroidal invasion. Immunohistochemistry revealed positive
      staining in tumor cells with 4 antibodies. Tight cellular junctions specific to
      the RPE were confirmed by electron microscopy. The final diagnosis was RPE
      adenocarcinoma. Conclusions: Most pigmented intraocular tumors are nevus and
      malignant melanomas of the choroid. It is easy to misdiagnose a RPE
      adenocarcinoma as a malignant melanoma of the choroid. An exact differential
      diagnosis should be determined by immunohistopathological and electron
      microscopic examination.

PMID- 29344498
TI  - Selective Intra-Arterial Embolization for Advanced Extrascleral Uveal Melanoma.
AB  - Purpose: To report a treatment approach for advanced extrascleral uveal melanoma.
      Methods: We performed clinical examination including magnetic resonance imaging,
      computed tomography, angiography, and histopathologic analysis. Case: A 49-year
      old healthy woman presented with a 7-year history of an enlarging pigmented mass
      in her right orbit. Malignant melanoma was diagnosed after biopsy with
      immunohistochemical stains. Treatment included selective intra-arterial
      embolization. Results: A significant reduction in tumor burden was seen 3 months
      after intra-arterial embolization. No complications were associated with the
      treatment. Conclusion: Selective intra-arterial embolization may allow adequate
      palliative therapy in select cases of advanced extrascleral uveal melanoma.

PMID- 29344499
TI  - Unilateral Multifocal Choroidal Melanoma.
AB  - We report a case of multifocal choroidal melanoma in the same eye, separated in
      presentation by 20 years. A 57-year-old Caucasian male initially presented with a
      choroidal melanoma of the right eye that was treated with transpupillary
      thermotherapy. Due to recurrence, the patient underwent proton beam therapy with
      subsequent tumor regression. A second small choroidal lesion was noted in the
      right eye during his surveillance examinations that was closely monitored and
      demonstrated stable dimensions and features suggestive of a choroidal nevus.
      Twenty years after his first presentation, the second lesion exhibited
      accelerated growth with imaging studies indicative of transformation to a
      distinct choroidal melanoma. The patient underwent a second globe salvage
      treatment of proton beam therapy. We describe the clinical course, radiographic,
      and imaging findings of this rare choroidal melanoma.

PMID- 29344500
TI  - Pilot Study of a "Large-Eye," Surgically Induced Dry Eye Rabbit Model by
      Selective Removal of the Harderian, Lacrimal, and Meibomian Glands.
AB  - Background/Aims: Establish a reliable rabbit dry eye (DE) model. Methods: An
      interventional cohort study surgically removing glands contributing to the tear
      film. Eight rabbits were studied after removal of left lacrimal, Harderian, or
      both glands. Additional rabbits had Meibomian glands in the left eye thermally
      obstructed. All were followed for 10 weeks with phenol red thread (PRT) and slit
      lamp examination with 2% fluorescein. We assessed corneal sensitivity using a
      Cochet-Bonnet esthesiometer. Outcome measures were severity/duration of reduced
      PRT, punctate epithelial erosions (PEE), and histologic evidence of corneal
      pannus. Results: Fluorescein staining demonstrated signs of dryness including PEE
      in all of the interventional eyes. The subjective measurement of epithelial
      erosions correlated with decreased tear production. PRT measurements in the
      control eyes averaged 31.54 mm (+/-1.83) and 22.71 mm (+/-1.60) in the eight left
      eyes, without loss of corneal sensitivity. Conclusions: Surgical removal of
      either the Harderian or lacrimal gland results in statistically significant
      decreases in tear volume and the development of severe DE. Removal of both glands
      results in the occurrence of a DE of comparable severity/duration to removal of
      either the lacrimal or Harderian gland alone. Meibomian gland obstruction
      contributes less to the DE model.

PMID- 29344501
TI  - Pigmented Epithelioid Melanocytoma of the Cheek, Orbit, and Intracranial Cavity:
      A Case Report.
AB  - Pigmented epithelioid melanocytoma (PEM) of the skin has been rarely reported in
      ophthalmology. The purpose of this case report is to present a young male born
      with a progressive, hyperpigmented lesion involving the orbit and intracranial
      cavity diagnosed as PEM. The case is unique given the young age and the size,
      multifocality, and growth of this tumor. Identification of this lesion is
      paramount due to its low-grade malignant potential.

PMID- 29344502
TI  - Orbital Epstein-Barr Virus-Positive Polymorphic B-Cell Lymphoproliferative
      Disorder in an Apparently Immunocompetent Woman.
AB  - We report a rare case of Epstein-Barr virus (EBV)-positive polymorphic B-cell
      lymphoproliferative disorder (LPD) involving the lacrimal gland of a 28-year-old,
      apparently immunocompetent woman. She presented with a chief complaint of orbital
      swelling and tenderness and was found to have a lesion involving the right
      lacrimal gland and distal superior and lateral rectus muscles. Histology of the
      lesion revealed histiocytes with pleomorphic nuclei, reactive lymphocytes, and
      scattered cells that resembled the Reed-Sternberg (R-S) cells of classical
      Hodgkin lymphoma. The R-S-like cells were positive for PAX5 and CD30 and negative
      for CD15, supporting a diagnosis of polymorphic B-cell LPD. In situ hybridization
      for EBV-encoded RNA demonstrated the presence of EBV. Most EBV-positive
      polymorphic B-cell LPDs are associated with immunodeficiency. However, the
      patient described is HIV-negative and has no identifiable defects in
      immunoglobulin levels or cell-mediated immunity. This raises the question of
      whether she has an underlying immunodeficiency resulting from subtle changes in T
      cell physiology, or whether chronic EBV infection contributed to her immune
      dysfunction through an unclear mechanism. The orbital mass partially regressed
      with chemotherapy, and the patient has done well clinically with no recurrence of
      this EBV-LPD for over 2 years.

PMID- 29344504
TI  - New Findings on the Pathogenesis of Distal Renal Tubular Acidosis.
AB  - Background: Distal renal tubular acidosis (dRTA) is characterized by an
      impairment of the urinary acidification process in the distal nephron. Complete
      or incomplete metabolic acidosis coupled with inappropriately alkaline urine are
      the hallmarks of this condition. Genetic forms of dRTA are caused by loss of
      function mutations of either SLC4A1, encoding the AE1 anion exchanger, or
      ATP6V1B1 and ATP6V0A4, encoding for the B1 and a4 subunits of the vH+ATPase,
      respectively. These genes are crucial for the function of A-type intercalated
      cells (A-IC) of the distal nephron. Summary: Alterations of acid-base homeostasis
      are variably associated with hypokalemia, hypercalciuria, nephrocalcinosis or
      nephrolithiasis, and a salt-losing phenotype. Here we report the diagnostic test
      and the underlying physiopathological mechanisms. The molecular mechanisms
      identified so far can explain the defect in acid secretion, but do not explain
      all clinical features. We review the latest experimental findings on the
      pathogenesis of dRTA, reporting mechanisms that are instrumental for the
      clinician and potentially inspiring a novel therapeutic strategy. Key Message:
      Primary dRTA is usually intended as a single-cell disease because the A-IC are
      mainly affected. However, novel evidence shows that different cell types of the
      nephron may contribute to the signs and symptoms, moving the focus from a single
      cell towards a renal disease.

PMID- 29344503
TI  - Genetics of Magnesium Disorders.
AB  - Background: Magnesium (Mg2+), the second most abundant cation in the cell, is
      woven into a multitude of cellular functions. Dysmagnesemia is associated with
      multiple diseases and, when severe, can be life-threatening. Summary: This review
      discusses Mg2+ homeostasis and function with specific focus on renal Mg2+
      handling. Intrarenal channels and transporters related to Mg2+ absorption are
      discussed. Unraveling the rare genetic diseases with manifestations of
      dysmagnesemia has greatly increased our understanding of the complex and
      intricate regulatory network in the kidney, specifically, functions of tight
      junction proteins including claudin-14, -16, -19, and -10; apical ion channels
      including: TRPM6, Kv1.1, and ROMK; small regulatory proteins including AC3 and
      ANK3; and basolateral proteins including EGF receptor, gamma-subunit (FXYD2) of
      Na-K-ATPase, Kir4.1, CaSR, CNNM2, and SLC41A. Although our understanding of Mg2+
      handling of the kidney has expanded considerably in the last two decades, many
      questions remain. Future studies are needed to elucidate a multitude of unknown
      aspects of Mg2+ handling in the kidney. Key Message: Understanding rare and
      genetic diseases of Mg2+ dysregulation has expanded our knowledge and furthers
      the development of strategies for preventing and managing dysmagnesemia.

PMID- 29344505
TI  - Genome-Wide Analysis Studies and Chronic Kidney Disease.
AB  - In recent years, the very high worldwide prevalence of chronic kidney disease
      (CKD) has led some authors to talk of an "epidemic." The progression of CKD
      varies considerably among individuals despite similar aetiologies, optimal blood
      pressure, and glycaemic control. Over the last decade, through genome-wide
      association studies (GWAS), more than 50 genetic loci have been identified in
      association with CKD. Understanding the genetic basis of CKD could provide a
      better knowledge of the biology of the involved pathways, thus potentially
      leading to novel tools for the diagnosis, prevention, and therapy of CKD. In this
      review, we will analyse the role of GWAS in the study of CKD.

PMID- 29344506
TI  - MicroRNAs in Renal Diseases: A Potential Novel Therapeutic Target.
AB  - Background: MicroRNAs (miRNAs) are a family of short noncoding RNAs that play
      important roles in posttranscriptional gene regulation. miRNAs inhibit target
      gene expression by blocking protein translation or by inducing mRNA degradation
      and therefore have the potential to modulate physiological and pathological
      processes. Summary: In the kidney, miRNAs play a role in the organogenesis and in
      the pathogenesis of several diseases, including renal carcinoma, diabetic
      nephropathy, cystogenesis, and glomerulopathies. Indeed, podocytes, but also the
      parietal cells of the Bowman capsule are severely affected by miRNA deregulation.
      In addition, several miRNAs have been found involved in the development of renal
      fibrosis. These experimental lines of evidence found a counterpart also in
      patients affected by diabetic and Ig-A nephropathies, opening the possibility of
      their use as biomarkers. Finally, the possibility to direct target-specific miRNA
      to prevent the development of renal fibrosis is encouraging potential novel
      therapies based on miRNA mimicking or antagonism. This review reports the main
      studies that investigate the role of miRNAs in the kidneys, in particular
      highlighting the experimental models used, their potential role as biomarkers
      and, finally, the most recent data on the miRNA-based therapy. Key Messages:
      miRNAs are crucial regulators of cell function. They are easy to detect and
      represent potentially good targets for novel therapies.

PMID- 29344507
TI  - Definition, Management, and Outcomes of Acute Kidney Injury: An International
      Survey of Nephrologists.
AB  - Background: Acute kidney injury (AKI) is a complex disease burdened by
      uncertainties of definition, management strategies, and prognosis. This study
      explores the relationship between demographic characteristics of nephrologists
      and their perceptions about the definition, management, and follow-up of AKI.
      Methods: We developed a Web-based survey, the International Survey on Acute
      Kidney Injury (ISAKI), consisting of 29 items in 4 categories: (1) demographic
      and practice characteristics, (2) definition of AKI, (3) management of renal
      replacement therapy (RRT) in AKI, and (4) sequelae of AKI. A multivariable
      stepwise logistic regression model was used to examine relationships between the
      dependent variables and the demographic characteristics of the respondents.
      Results: Responses from 743 nephrologists from 90 countries were analyzed. The
      majority (60%) of respondents reported using RIFLE and/or AKIN criteria regularly
      to define AKI, although US nephrologists were less likely to do so (OR: 0.58; 95%
      CI: 0.42-0.85). The most common initial RRT modality was intermittent
      hemodialysis (63.5%), followed by continuous RRT (23.8%). Faculty affiliation was
      associated with a higher likelihood of using a dialysis schedule of >=4 times a
      week (OR: 1.75; 95% CI: 1.20-2.55). The respondents believed that a single
      episode of AKI increases the likelihood of development of chronic kidney disease
      (CKD) (55%), subsequent AKI (36%), and rapid progression of preexisting CKD
      (87%). US nephrologists were less likely to recommend follow-up after resolution
      of AKI (OR: 0.15; 95% CI: 0.07-0.33). Conclusions: Our findings highlight the
      need for a widely accepted consensus definition of AKI, a uniform approach to
      management, and improved follow-up after resolution of AKI episodes.

PMID- 29344508
TI  - Acid-Base and Electrolyte Disorders in Patients with and without Chronic Kidney
      Disease: An Update.
AB  - Kidneys play a pivotal role in the maintenance and regulation of acid-base and
      electrolyte homeostasis, which is the prerequisite for numerous metabolic
      processes and organ functions in the human body. Chronic kidney diseases
      compromise the regulatory functions, resulting in alterations in electrolyte and
      acid-base balance that can be life-threatening. In this review, we discuss the
      renal regulations of electrolyte and acid-base balance and several common
      disorders including metabolic acidosis, alkalosis, dysnatremia, dyskalemia, and
      dysmagnesemia. Common disorders in chronic kidney disease are also discussed. The
      most recent and relevant advances on pathophysiology, clinical characteristics,
      diagnosis, and management of these conditions have been incorporated.

PMID- 29344509
TI  - Review of the Diagnostic Evaluation of Normal Anion Gap Metabolic Acidosis.
AB  - Background: Normal anion gap metabolic acidosis is a common but often
      misdiagnosed clinical condition associated with diarrhea and renal tubular
      acidosis (RTA). Early identification of RTA remains challenging for inexperienced
      physicians, and diagnosis and treatment are often delayed. Summary: The presence
      of RTA should be considered in any patient with a high chloride level when the CL
      /Na+ ratio is above 0.79, if the patient does not have diarrhea. In patients with
      significant hyperkalemia one should evaluate for RTA type 4, especially in
      diabetic patients, with a relatively conserved renal function. A still growing
      list of medications can produce RTA. Key Messages: This review highlights
      practical aspects concerning normal anion gap metabolic acidosis.

PMID- 29344510
TI  - Ablation of FGFR2 in Fibroblasts Ameliorates Kidney Fibrosis after
      Ischemia/Reperfusion Injury in Mice.
AB  - Background: Fibroblast growth factors (FGFs) are heparin-binding proteins
      involved in a variety of biological processes. However, the role and mechanisms
      of FGF/FGFR2 signaling in fibroblast activation and kidney fibrosis need further
      investigation. Methods: In this study, a mouse model with fibroblast-specific
      FGFR2 gene disruption was generated. The knockouts were born normal and no kidney
      dysfunction or histological abnormality was found within 2 months after birth. A
      kidney ischemia/reperfusion injury (IRI) model was created. Results: Kidney
      fibrosis was developed in the control littermates within 2 and 4 weeks after IRI,
      while in the knockouts, total collagen deposition, fibronectin, and alpha smooth
      muscle actin expression were decreased compared to those in the control
      littermates. In addition, the numbers of Ki-67-positive interstitial cells as
      well as TUNEL-positive interstitial cells were lower in the knockout kidneys at 4
      weeks after IRI. Phosphorylated extracellular regulated protein kinase 1/2 was
      decreased in the knockout kidneys at 2 and 4 weeks after IRI compared to those in
      the control littermates. Conclusion: These results suggest that FGF/FGFR2
      signaling may promote the proliferation and activation of kidney fibroblasts,
      which contribute to the development of kidney fibrosis.

PMID- 29344512
TI  - Frontiers of Liver Surgery.

PMID- 29344511
TI  - Crosstalk of Hyperglycemia and Dyslipidemia in Diabetic Kidney Disease.
AB  - Background: Diabetic kidney disease (DKD) is defined by the functional,
      structural, and clinical abnormalities of the kidney that are caused by diabetes.
      Summary: One-third of both type 1 diabetes and type 2 diabetes patients suffer
      from DKD, which is the leading cause of end-stage renal disease, and is also
      associated with cardiovascular disease and high public health care costs. Serum
      glucose level and lipid level are key factors in the pathogenesis of DKD and are
      modifiable. The goal of this review is to provide an update on the roles of
      glucose and lipid metabolism in DKD and their crosstalk at the molecular level.
      We will further discuss the recent advances regarding metabolic nuclear receptors
      in glucose-lipid crosstalk, which may provide new potential therapeutic targets
      for DKD. Key Message: AMPK, SREBP-1, and some metabolic hormone receptors
      including liver X receptors, farnesoid X receptors, and peroxisome proliferator
      activated receptors mediate the crosstalk of hyperglycemia and dyslipidemia in
      diabetic kidney disease and might be potential treatment candidates.

PMID- 29344513
TI  - 'In-Situ Split' Liver Resection/ALPPS - Historical Development and Current
      Practice.
AB  - Background: Liver tumors that are extensive, multifocal, or critically located
      frequently require advanced techniques of liver resection including '!' -
      enabling liver resection in certain situations. Methods: The development of the
      technique in the first and the subsequent 8 patients in the index center, and
      also the method's spread throughout Germany and the world were reviewed. Results:
      In 2007, in the first patient, the new technique was developed intraoperatively
      by necessity. Due to the convincing outcome, it was deliberately applied again
      several months later in another patient, and thereafter (sparsely) used for liver
      resection for various indications. Following oral communication, the method
      spread throughout Germany, and later - mainly following the publication of the
      initial multicentric German series - very quickly disseminated worldwide.
      Currently, it is used for a very (if not overly) broad spectrum of indications by
      many hepatobiliary surgery centers. Conclusion: In-situ split/ALPPS is a newly
      developed technique for liver resection, which was established for very specific
      situations. This method has created a hype, and is currently used rather
      generously by many centers worldwide.

PMID- 29344514
TI  - Portal Vein Embolization: History and Current Indications.
AB  - Portal vein embolization (PVE) was first adapted for patients undergoing major
      hepatectomy for hepatocellular carcinoma (HCC). In these patients, PVE caused
      hypertrophy of the unaffected liver and increased the volumetric ratio of future
      liver remnant (FLR) to total liver volume. 99mTechnetium-galactosyl human serum
      albumin (99mTc-GSA) scintigraphy revealed that PVE also induced a shift in
      hepatic function from the embolized part to the nonembolized part of the liver.
      Various hepatobiliary malignancies can be treated using PVE, and PVE is
      increasingly being used to expand the indication for major hepatectomy in
      patients with initially insufficient FLR volume or function. The indication for
      PVE is determined by the underlying liver function and standardized FLR volume.
      In patients with chronic hepatitis, the histologic inflammatory activity was
      negatively correlated with the increase in FLR volume, and PVE is not suitable
      for patients with high serum 7s collagen concentrations (>8 ng/ml). This finding
      may predict the efficacy of PVE. PVE before major hepatectomy can act as a
      tolerance test to avoid postoperative hepatic failure. PVE also improved long
      term survival after liver resection in patients with HCC. Presently, PVE is a
      safe and useful treatment for patients undergoing major hepatectomy.

PMID- 29344515
TI  - Portal Vein Embolization: State-of-the-Art Technique and Options to Improve Liver
      Hypertrophy.
AB  - Portal vein embolization (PVE) is associated with a high technical and clinical
      success rate for induction of future liver remnant hypertrophy prior to surgical
      resection. The degree of hypertrophy is variable and depends on multiple factors,
      including technical aspects of the procedure and underlying chronic liver
      disease. For patients with insufficient liver volume following PVE, adjunctive
      techniques, such as intra-portal administration of stem cells, dietary
      supplementation, transarterial embolization, and hepatic vein embolization, are
      available. Our purpose is to review the state-of-the-art technique associated
      with high-quality PVE and to discuss options to improve hypertrophy of the future
      liver remnant.

PMID- 29344516
TI  - Hypertrophy and Liver Function in ALPPS: Correlation with Morbidity and
      Mortality.
AB  - Background: ALPPS (associating liver partition and portal vein ligation for
      staged hepatectomy) was introduced with the promise to reduce posthepatectomy
      liver failure (PHLF) in extended hepatectomies but has higher morbidity and
      mortality rates compared to conventional methods of volume enhancement. There are
      few studies of the incidence of PHLF after ALPPS and little information on how to
      avoid PHLF by functional testing. It remains unclear what causes the compromise
      in liver function despite rapid volume gain and if any of the modifications
      proposed reduce the incidence of PHLF. This review summarizes published data on
      this topic. Methods: This is a systematic review that studies literature on the
      incidence of liver failure and assessment of liver function following ALPPS as
      well as modifications of the existing technique. Articles were searched in
      PubMed, evaluated, selected, and tabulated. Results: The literature search
      revealed 326 articles that met the selection criteria. PHLF criteria as defined
      by the International Study Group of Liver Surgery (ISGLS) were the most commonly
      used criteria, but PHLF was frequently not defined. PHLF occurred most frequently
      after stage 2 of ALPPS at around 30% in most larger studies. Hepatobiliary
      scintigraphy showed a discrepancy between volume and functional growth of the
      liver. Function increase was only 50% compared to volume increase. Mechanistic
      explanations using histologic analyses have been given to explain the immaturity
      of the liver after rapid hypertrophy. Modifications of ALPPS showed a comparable
      volumetric gain when compared to classic ALPPS, but data were lacking to assess
      PHLF. Conclusion: ALPPS has relatively high rates of PHLF, morbidity, and
      mortality. This may be explained by data demonstrating functional growth when
      compared to volume growth. ALPPS should not be performed without functional
      assessment and with caution.

PMID- 29344517
TI  - A Comparison of Pitfalls after ALPPS Stage 1 or Portal Vein Embolization in Small
      for-Size Setting Hepatectomies.
AB  - Background: Portal vein embolization (PVE) followed by resection and associating
      liver partition and portal vein ligation for staged hepatectomy (ALPPS) are tools
      to enable liver resections in small-for-size settings. Methods: A systematic
      review of the literature and comparison of pitfalls between PVE and resection and
      after ALPPS stage 1 were performed. Results: Evidence levels were as low as 4 for
      both procedures. 20 publications were identified with reports on post-PVE or post
      ALPPS stage 1 pitfalls. A total of 2,758 patients treated with PVE followed by
      resection and 698 patients undergoing ALPPS were analyzed. Pitfalls identified
      were failure to advance to resection (PVE: high (20%)/ALPPS: low (1%); p =
      0.0001), tumor progression (PVE: high/ALPPS: low); insufficient hypertrophy (PVE:
      frequent/ALPPS: rare), and inter-stage liver failure (PVE: rare/ALPPS: frequent).
      However, in-house mortality was still very high after ALPPS (7 vs. 3%, p =
      0.0001) in a pooled analysis. Conclusion: PVE is a well-established technique to
      induce hypertrophy in small-for-size settings. The weakness of PVE is that it may
      fail to advance to resection. Inter-stage liver failure in ALPPS triggers post
      stage 2 mortality. Prolongation of the inter-stage interval to overcome liver
      failure or cancellation of the resection stage combined with adherence to defined
      indications has the potential to make ALPPS much safer and decrease mortality
      rates. Level of evidence is low for both techniques.

PMID- 29344518
TI  - Current Modalities for the Assessment of Future Remnant Liver Function.
AB  - While imaging studies such as computed tomography or magnetic resonance imaging
      allow the volumetric assessment of the liver segments, only indirect information
      is provided concerning the quality of the liver parenchyma and its actual
      functional capacity. Assessment of liver function is therefore crucial in the
      preoperative workup of patients who require extensive liver resection and in whom
      portal vein embolization is considered. This review deals with the modalities
      currently available for the measurement of liver function. Passive liver function
      tests include biochemical parameters and clinical grading systems such as the
      Child-Pugh and MELD scores. Dynamic quantitative tests of liver function can be
      based on clearance capacity tests such as the indocyanine green (ICG) clearance
      test. Although widely used, discrepancies have been reported for the ICG
      clearance test in relation with clinical outcome. Nuclear imaging studies have
      the advantage of providing simultaneous morphologic (visual) and physiologic
      (quantitative functional) information about the liver. In addition, regional
      (segmental) differentiation allows specific functional assessment of the future
      remnant liver. Technetium-99m (99mTc)-galactosyl human serum albumin scintigraphy
      and 99mTc-mebrofenin hepatobiliary scintigraphy potentially identify patients at
      risk for post-resectional liver failure who might benefit from liver-augmenting
      techniques. As there is no one test that can measure all the components of liver
      function, liver functional reserve is estimated based on a combination of
      clinical parameters and quantitative liver function tests.

PMID- 29344519
TI  - ICG Clearance Test and 99mTc-GSA SPECT/CT Fusion Images.
AB  - Preoperative estimation of future remnant liver function is critical for major
      hepatic surgery to avoid postoperative morbidity and mortality. Among several
      liver function tests, the indocyanine green (ICG) clearance test is still the
      most popular dynamic method. The usefulness of ICG clearance test parameters,
      such as ICGR15, KICG, or PDRICG, has been reported by many investigators. The
      transcutaneous non-invasive pulse dye densitometry system has made the ICG
      clearance test more convenient and attractive, even in Western countries. The
      concept of future remnant KICG (rem KICG), which combines the functional aspect
      and the volumetric factor of the future remnant liver, seems ideal for
      determining the maximum extent of major hepatic resection that will not cause
      postoperative liver failure. For damaged livers with functional heterogeneity
      among the hepatic segments, fusion images combining technetium-99m
      diethylenetriaminepentaacetic acid-galactosyl human serum albumin single photon
      emission computed tomography (99mTc-GSA SPECT) and X-ray CT are helpful to
      precisely estimate the functional reserve of the future remnant liver. Another
      technique for image-based liver function estimation, gadolinium ethoxybenzyl
      diethylenetriamine pentaacetic acid(Gd-EOB)-enhanced magnetic resonance imaging,
      may be an ideal candidate for the preoperative determination of future remnant
      liver function. Using these methods effectively, morbidity and mortality after
      major hepatic resection could be reduced.

PMID- 29344521
TI  - Frontiers of Liver Surgery.

PMID- 29344520
TI  - Did the International ALPPS Meeting 2015 Have an Impact on Daily Practice? The
      Hamburg Barmbek Experience of 58 Cases.
AB  - Background: ALPPS (associating liver partition and portal vein ligation for
      staged hepatectomy) was introduced only 10 years ago and has gained wide
      acceptance as a variation of staged procedures in liver surgery. It has been
      criticized for its high morbidity and mortality, which all centers reported in
      their initial series. Methods: After a world expert meeting in Hamburg in 2015
      where all experts in the field met to discuss this method, caveats were extracted
      and formulated. We researched our complete prospective ALPPS database to see if
      the recommendations had any impact on outcome. Results: In total, we performed 58
      ALPPS procedures in our center. 33 patients were operated on before, 25 after the
      meeting. Results in terms of morbidity and mortality were significantly better
      after the meeting, as were patient selection and strategy. Conclusion: In our own
      center's experience, the implementation of the meetings' recommendations and the
      information gathered through this valuable exchange had a dramatic impact on
      results. Having performed 58 ALPPS procedures in total, we can now conclude that
      ALPPS has become much safer in our hands since the 2015 meeting and that
      morbidity and mortality are no longer the issue to be discussed. Future research
      must focus on oncologic outcomes in these patients.

PMID- 29344524
TI  - The Professionalization of Iranian hospital social Workers.
AB  - Introduction: Identity is formed through our understanding of ourselves and what
      others perceive of our actions and how we do things. Formation of professional
      identity includes development, advancement and socialization through social
      learning of specific knowledge and skills obtained within the context of
      professional roles, new attitudes and values. Methods: This qualitative study
      used content analysis approach to explain the professionalization process of 22
      social workers working in 14 public hospitals in Tehran based on their
      experiences. The data were collected through semi-structured interviews,
      observation and writing in the field. Results: Eleven categories and three themes
      of entry into the profession, identity formation, and identity ownership were
      extracted out of data analysis. Revealing the process, barriers and facilitators
      of professionalization of hospital social workers was the results of this study.
      Conclusion: Certain individual characteristics were factors for the tendency of
      participants to choose this profession. The participants' understanding of their
      profession was formed, when studying in the university through learning relevant
      knowledge, skills, views and professional expectations. Achieving a single
      identity and professional pride and self-esteem are achievements of identity
      ownership.

PMID- 29344522
TI  - Intraductal Papillary Mucinous Neoplasms of the Pancreas: Strategic
      Considerations.
AB  - Intraductal papillary mucinous neoplasms (IPMN) are cystic neoplasms with the
      potential for progression to pancreatic cancer. Recognized by the global medical
      community just over two decades ago, IPMN have gained great epidemiological and
      clinical relevance thanks to the widespread use of cross-sectional abdominal
      imaging, which has led to a surge in the number of incidental pancreatic cysts
      being diagnosed. As our understanding of this disease has improved, we now know
      that some IPMN have a very elevated risk of cancer and require surgical
      resection, while others are low-risk lesions and can be followed. The approach to
      IPMN must therefore strike a balance between preventing the over-utilization of
      surgery and the timely recognition and treatment of patients with high-risk
      lesions. Several clinical, radiographic, and laboratory parameters have been
      proposed to risk-stratify IPMN, leading to the publication of management
      guidelines that do not always converge in their recommendations. The goal of this
      clinical therapeutic review is to describe the strategic approach to IPMN at the
      Massachusetts General Hospital, and how our current understanding, management
      algorithm, and future directions have been informed by research efforts at our
      institution and other centers.

PMID- 29344523
TI  - Clinical skills temporal degradation assessment in undergraduate medical
      education.
AB  - Introduction: Medical students' ability to learn clinical procedures and
      competently apply these skills is an essential component of medical education.
      Complex skills with limited opportunity for practice have been shown to degrade
      without continued refresher training. To our knowledge there is no evidence that
      objectively evaluates temporal degradation of clinical skills in undergraduate
      medical education. The purpose of this study was to evaluate temporal retention
      of clinical skills among third year medical students. Methods: This was a cross
      sectional study conducted at four separate time intervals in the cadaver
      laboratory at a public medical school. Forty-five novice third year medical
      students were evaluated for retention of skills in the following three
      procedures: pigtail thoracostomy, femoral line placement, and endotracheal
      intubation. Prior to the start of third-year medical clerkships, medical students
      participated in a two-hour didactic session designed to teach clinically relevant
      materials including the procedures. Prior to the start of their respective
      surgery clerkships, students were asked to perform the same three procedures and
      were evaluated by trained emergency medicine and surgery faculty for retention
      rates, using three validated checklists. Students were then reassessed at six
      week intervals in four separate groups based on the start date of their
      respective surgical clerkships. We compared the evaluation results between
      students tested one week after training and those tested at three later dates for
      statistically significant differences in score distribution using a one-tailed
      Wilcoxon Mann-Whitney U-test for non-parametric rank-sum analysis. Results:
      Retention rates were shown to have a statistically significant decline between
      six and 12 weeks for all three procedural skills. Conclusion: In the instruction
      of medical students, skill degradation should be considered when teaching complex
      technical skills. Based on the statistically significant decline in procedural
      skills noted in our investigation, instructors should consider administering a
      refresher course between six and twelve weeks from initial training.

PMID- 29344525
TI  - Psychometric properties of the communication skills attitude scale (CSAS) measure
      in a sample of Iranian medical students.
AB  - Introduction: Communication skill (CS) has been regarded as one of the
      fundamental competencies for medical and other health care professionals.
      Student's attitude toward learning CS is a key factor in designing educational
      interventions. The original CSAS, as positive and negative subscales, was
      developed in the UK; however, there is no scale to measure these attitudes in
      Iran. The aim of this study was to assess the psychometric characteristic of the
      Communication Skills Attitude Scale (CSAS), in an Iranian context and to
      understand if it is a valid tool to assess attitude toward learning communication
      skills among health care professionals. Methods: Psychometric characteristics of
      the CSAS were assessed by using a cross-sectional design. In the current study,
      410 medical students were selected using stratified sampling framework. The face
      validity of the scale was estimated through students and experts' opinion.
      Content validity of CSAS was assessed qualitatively and quantitatively.
      Reliability was examined through two methods including Chronbach's alpha
      coefficient and Intraclass Correlation of Coefficient (ICC). Construct validity
      of CSAS was assessed using confirmatory factor analysis (CFA) and explanatory
      factor analysis (PCA) followed by varimax rotation. Convergent and discriminant
      validity of the scale was measured through Spearman correlation. Statistical
      analysis was performed using SPSS 19 and EQS, 6.1. Results: The internal
      consistency and reproducibility of the total CSAS score were 0.84 (Cronbach's
      alpha) and 0.81, which demonstrates an acceptable reliability of the
      questionnaire. The item-level content validity index (I-CVI) and the scale-level
      content validity index (S-CVI/Ave) demonstrated appropriate results: 0.97 and
      0.94, respectively. An exploratory factor analysis (EFA) on the 25 items of the
      CSAS revealed 4-factor structure that all together explained %55 of the variance.
      Results of the confirmatory factor analysis indicated an acceptable goodness-of
      fit between the model and the observed data. [chi2/df = 2.36, Comparative Fit
      Index (CFI) = 0.95, the GFI=0.96, Root Mean Square Error of Approximation (RMSEA)
      = 0.05]. Conclusion: The Persian version of CSAS is a multidimensional, valid and
      reliable tool for assessing attitudes towards communication skill among medical
      students.

PMID- 29344527
TI  - Medical students' experiences and perspective on unprofessional behavior in
      clinical practice.
AB  - Introduction: Recognition of professional and unprofessional behaviors is the
      most important and fundamental factor which affects the relationships between the
      doctors and patients. Therefore, in order to progress in their professional life,
      doctors are supposed to understand and follow these behaviors. Methods: This is a
      cross-sectional, descriptive analytical study. All students in teaching hospital
      of Shiraz University of Medical Sciences were eligible to participate (374
      individuals with census method). The data were collected using a questionnaire
      containing 29 questions about the concept of medical professionalism. Here,
      participation of medical students in unprofessional behaviors and the relevance
      of this participation with the perception of these behaviors were considered.
      Data were analyzed through SPSS version 15, using descriptive statistics, t-test
      and Pearson correlation test. Results: According to the obtained data, despite
      the fact that all students (140 students in the junior and 234 in the senior
      years as interns) had passed the course of professionalism (95.7%), the
      perception of unprofessional behaviors between the two groups was significantly
      different (p<0.001) and the mean of the perception among junior students was
      higher than the interns. No significant difference was observed in participation
      in unprofessional behavior rates of the two groups (p=0.451).Moreover, the data
      did not reveal a strong relationship between participation in unprofessional
      behavior and what is taught in the curriculum (p=0.079). Conclusion: Medical
      students' perception of unprofessional behaviors as acceptable may increase their
      participation in these behaviors. Thus, medical policy makers should consider
      approaches beyond simply providing ethical and professional guidelines or
      policies, and students should be regularly evaluated for their activities; their
      professional behaviors should be evaluated in order to temper them, when
      appropriate.

PMID- 29344526
TI  - The effects of team-based learning on learning outcomes in a course of
      rheumatology.
AB  - Introduction: We evaluated the effects of implementing Team-Based Learning (TBL)
      on student engagement, accountability, satisfaction, and preference for lecture
      or team-based learning. Moreover, we assessed the effect of TBL on knowledge
      retention and application over time through short answer questions based on
      clinical scenarios addressing history taking and diagnosis skills in medical
      students. Methods: The study was conducted in a quasi-experimental design. The
      study population were all of the third-year medical students (n = 84)
      participating in a course of rheumatology in Shariati Hospital, which is a
      teaching hospital affiliated to Tehran University of Medical Sciences. We
      compared TBL with the conventional lecture-based method. The assessments were
      performed after implementation of TBL by the Classroom Engagement Survey (CES)
      and Team-Based Learning Student Assessment Instrument (TBL-SAI). The assessment
      for application of knowledge was conducted in 3 time-points through short answer
      questions on rheumatic diseases. The comparison of results was made by Student's
      t-test and repeated-measures analysis of variance (RM-ANOVA) using SPSS software,
      version 16. Results: The CES scores indicated a high level of engagement in TBL
      (Mean+/-SD=26.7+/-3.70, p=0.0001) but not in the lecture-based sessions (Mean+/
      SD=23.80+/-4.35, p=0.09). The total mean score (SD) for TBL-SAI was 159.68
      (14.14) for TBL sessions indicating a favorable outcome (p=0.0001). The student
      scores obtained from the short answer questions showed that over time the
      students' scores had declined significantly less for the TBL sessions in
      comparison to the lecture-based sessions, F (2, 166) = 4.624, p=0.011.
      Conclusion: The results indicated higher student engagement, satisfaction and
      long term learning by TBL.

PMID- 29344528
TI  - Psychometric characteristics of Clinical Reasoning Problems (CRPs) and its
      correlation with routine multiple choice question (MCQ) in Cardiology department.
AB  - Introduction: Clinical reasoning is one of the most important skills in the
      process of training a medical student to become an efficient physician.
      Assessment of the reasoning skills in a medical school program is important to
      direct students' learning. One of the tests for measuring the clinical reasoning
      ability is Clinical Reasoning Problems (CRPs). The major aim of this study is to
      measure psychometric qualities of CRPs and define correlation between this test
      and routine MCQ in cardiology department of Shiraz medical school. Methods: This
      study was a descriptive study conducted on total cardiology residents of Shiraz
      Medical School. The study population consists of 40 residents in 2014. The
      routine CRPs and the MCQ tests was designed based on similar objectives and were
      carried out simultaneously. Reliability, item difficulty, item discrimination,
      and correlation between each item and the total score of CRPs were all measured
      by Excel and SPSS software for checking psycometeric CRPs test. Furthermore, we
      calculated the correlation between CRPs test and MCQ test. The mean differences
      of CRPs test score between residents' academic year [second, third and fourth
      year] were also evaluated by Analysis of variances test (One Way ANOVA) using
      SPSS software (version 20)(alpha=0.05). Results: The mean and standard deviation
      of score in CRPs was 10.19 +/-3.39 out of 20; in MCQ, it was 13.15+/-3.81 out of
      20. Item difficulty was in the range of 0.27-0.72; item discrimination was 0.30
      0.75 with question No.3 being the exception (that was 0.24). The correlation
      between each item and the total score of CRP was 0.26-0.87; the correlation
      between CRPs test and MCQ test was 0.68 (p<0.001). The reliability of the CRPs
      was 0.72 as calculated by using Cronbach's alpha. The mean score of CRPs was
      different among residents based on their academic year and this difference was
      statistically significant (p<0.001). Conclusion: The results of this present
      investigation revealed that CRPs could be reliable test for measuring clinical
      reasoning in residents. It can be included in cardiology residency assessment
      programs.

PMID- 29344529
TI  - Internationalization of medical education in Iran: A way towards implementation
      of the plans of development and innovation in medical education.
AB  - Introduction: Academic institutions are the most important organizations for
      implementation of internationalization policies and practices for integrating an
      international, intercultural and global dimension in higher education system.
      Also, a globally increasing demand for higher education has been seen in the past
      two decades so that the number of students enrolled in higher education
      institutions in the worldwide nation-states has increased dramatically. The
      National Plan of International Development of Medical Education was designed with
      the aim of identifying available potentials in all the universities of medical
      sciences, encouraging the development of international standards of medical
      education, and planning for the utilization of the existing capacity in Islamic
      republic of Iran. Methods: Authors have tried to review the several aspects of
      international activities in higher education in the world and describe national
      experiences and main policies in globalization of medical education in Iran
      within implementation of the National Plan for Development and Innovation in
      Medical Education. Results: The findings of some global experiences provide the
      policy makers with clear directions in order to develop internationalization of
      higher education. Conclusion: The Program for International Development of
      Medical Education was designed by the Deputy of Education in the Ministry of
      Health and the effective implementation of this Program was so important for
      promotion of Iranian medical education. But there were some challenges in this
      regard; addressing them through inter-sectoral collaboration is one of the most
      important strategies for the development of internationalization of education in
      the field of medical sciences.

PMID- 29344530
TI  - Female role models in medicine: a medical student's perspective.

PMID- 29344531
TI  - Factors Affecting the Place of Delivery among Mothers Residing in Jhorahat VDC,
      Morang, Nepal.
AB  - Background: In Nepal, the maternal mortality ratio is 281 per thousand live
      births, among which 40% mortality occurs during home delivery. Home delivery
      increases the risk of maternal and neonatal mortality and morbidity due to the
      birth not assisted by skilled attendant. This study was carried out to determine
      the factors affecting the place of delivery among the mothers residing in
      Jhorahat VDC, Morang district, Nepal. Methods: A mixed method study using
      interviews based on semi-structured questionnaire (n=93) among mothers and two
      focus group discussion among decision makers of the house and female community
      health volunteers was conducted between November to December 2012. For
      quantitative data, Chi-square test and Fischer's Exact test were used to examine
      the association between the selected variables and place of delivery. Results:
      More than half (58.1%) of the mothers had institutional delivery and 41.9% of
      them had home delivery. The most common reason for home delivery was easy and
      convenient environment (66.7%) and that for institutional delivery was safety
      (77.8%). There was a significant association between caste, education of mothers,
      education of spouse, occupation of spouse, per capita income, time to reach the
      nearest health center, parity, previous place of delivery, number of antenatal
      visit, knowledge about place of delivery, planned place of delivery, and place of
      delivery. Conclusion: Maternal health services, such as prenatal care, skilled
      assistance during delivery and post-natal care, along with adequately equipped
      health institutions, play a major role in the reduction of maternal morbidity and
      mortality. Concerted efforts should be made both at community and government
      levels to increase institutional delivery.

PMID- 29344532
TI  - Functional Ability of Clients with Bipolar Disorders in Tertiary Hospital,
      Puducherry.
AB  - Background: Bipolar Disorder (BD) is a common long standing mental illness which
      is episodic in nature, affecting approximately1-2% of the world adult population.
      BD frequently affects the patient's life. Few studies have examined the
      functional impairment in patients with affective illness. The main objective of
      the current study was to assess specific domains of functioning as well as the
      overall functioning of the clients with BD. Methods: This cross-sectional study
      aimed to assess the level of function among the clients with BD in JIPMER
      Hospital, Puducherry during 2015-2016 and to identify the socio- demographic and
      clinical factors associated with the level of functioning. Ninety clients who
      fulfilled the inclusion criteria of having the diagnosis of BD were selected
      after written informed consents were obtained. After collecting basic demographic
      and clinical variables, function was assessed using 2 different sets of tools
      LIFE-RIFT and FAST. Data were analyzed using SPSS 20. Independent sample t-test,
      ANOVA and Pearson correlation were used as different statistical methods. A P
      value less than .05 was considered as statistically significant. Results: Based
      on the results, the functional level assessed using LIFE -RIFT showed a mean
      score of 26.7+/-4.7for the admitted clients and 21+/-12.5 for outpatients. The
      functional level of clients was significantly related to admission and remission
      status of the clients with a P=0.001 Similarly, FAST scale score for the admitted
      clients was 51+/-4.5, clients on remission had 24+/-12.1 with a P=0.001.
      Conclusion: Results revealed that even during remission the clients with BD had
      functional impairment. More interventions are needed to improve the functional
      ability of clients with BD.

PMID- 29344533
TI  - The Effect of Family-Centered Empowerment Program on Self-Efficacy of Adolescents
      with Thalassemia Major: A Randomized Controlled Clinical Trial.
AB  - Background: Chronic nature of thalassemia causes changes in different aspects of
      life in patients, including their self-efficacy. The aim of this study was to
      determine the effect of family-centered empowerment program on the self-efficacy
      of adolescents with Thalassemia major. Methods: A quasi-experimental study was
      performed on adolescents with thalassemia major in 2013 in Bandar Abbas, Iran.
      The participants were divided into intervention and control groups, respectively.
      Research instruments included demographic data questionnaire, need assessment
      self-made questionnaire, general self-efficacy scale, and sickle cell self
      efficacy scale. After collecting the data from the pre-intervention step, family
      centered empowerment program was implemented for the intervention group and
      secondary test was conducted six weeks after the intervention and the results
      were analyzed by statistical SPSS-21 software, using independent t-test, paired t
      test, Chi-square and Fisher's exact test, and descriptive statistics. A
      significance level of P<0.05 was considered as significant. Results: The mean and
      standard deviation of the adolescents' age were 16+/-1.9 in the intervention
      group and 15.2+/-2 in the control group. Independent t-test showed a significant
      difference between the two groups after the intervention for both self-efficacies
      (P<0.01 and P=0.02). In the control group, the results of general self-efficacy
      scores after six weeks' time were reduced compared to the previous one while
      disease-related self-efficacy scores in the same group after six weeks' time
      increased and paired t-test indicated a significant difference in the mean scores
      for both self-efficacies in both groups. Conclusion: Implementation of family
      centered empowerment program for patients with thalassemia major is practically
      feasible and it can increase self-efficacy in these patients. It is suggested
      that the program should be used in comprehensive care protocols of children and
      adolescents. Trial Registration Number: IRCT201407211788N8.

PMID- 29344534
TI  - The Effect of Self-Care Education on Emotional Intelligence and HbA1c level in
      Patients with Type 2 Diabetes Mellitus: A Randomized Controlled Clinical Trial.
AB  - Background: The role of Emotional Intelligence (EI) in glycemic control in type 2
      Diabetes Mellitus (DM) has not been fully understood. The present study aimed to
      investigate the effect of self-care education on EI and hemoglobin glycosylated
      (HbA1c) in patients with type 2 diabetes. Methods: In this randomized controlled
      clinical trial, 48 patients with type 2 DM referred to Shahid Motahari Diabetes
      Center in 2015 were divided into an intervention and a control group using block
      randomization. The study data were collected using Bar-On questionnaire and blood
      testing immediately and two months after the intervention. The educational
      content was presented to the intervention group through 1-1:30-hour sessions held
      once a week for 8 continuous weeks. The control group, however, only received the
      clinic's routine cares. Results: The results showed a significant difference in
      the mean level of HbA1c in the intervention group before and two months after the
      intervention (P=0.003). However, this difference was not significant in the
      control group. Moreover, the mean of EI was higher in the intervention group
      compared to the control group (P=0.08). Conclusion: Self-care education improved
      the HbA1c level and EI among the patients with type 2 DM. Therefore, it is
      recommended that health care providers, specially nurses, should train the
      diabetic patients for self-care, which can lead to better glycemic control. Trial
      Registration Number: IRCT201408188505N7.

PMID- 29344535
TI  - Sexual Experience of Iranian Women in Their Middle Life: A Qualitative Approach.
AB  - Background: Sexual problems are common among the middle-aged women; however,
      there is no deep understanding of sexuality in midlife. The current study aimed
      to investigate Iranian women's attitudes and experiences about sexual life
      changes in midlife. Methods: This is a descriptive qualitative study. Seventeen
      women aged 40 -65 years old were purposively selected from urban health centers
      in Gorgan, Iran, in 2015. Face-to-face, semi-structured and in-depth interviews
      were conducted for data collection until data saturation was attained. The
      resulting data were analyzed based on Graneheim and Lundman's approach. MAXQDA 10
      was used for organization of data. Results: Data analysis demonstrated seventh
      sub-themes and three themes. The emerged themes were entitled (1) "Continuous
      paradox over being a sexual agent" with three subthemes of beliefs on asexuality
      as socially accepted view for women in midlife, changing in motivation for sex
      and changing in sexual performance, (2) "Considering menopause; opportunities and
      threats for sexual life" with two subthemes of menopause related cons for sexual
      life and menopause related pros in sexual life, and (3) "Coping strategies for
      changes in sexuality in midlife" with two subthemes of different psychological
      reactions to changes that have influenced the sex and take practical steps for
      restoration of sexual attraction. Conclusion: The findings demonstrated that
      middle-aged women in a male-dominant culture encounter paradox over being a
      sexual agent. In a bio-psycho-social approach, they perceived menopause as an
      opportunity or threat for their own sexuality. Following the conflicts, threats
      and changes of sexuality in midlife, they adopt diverse coping strategies to
      improve their sexual relationships and preserve their family.

PMID- 29344536
TI  - A Cry for Help and Protest: Self-Immolation in Young Kurdish Iraqi Women -A
      Qualitative Study.
AB  - Background: Suicide is a major psychiatric emergency that has always been a topic
      of great interest to researchers. Self-immolation is a heinous suicide method
      that is common in Eastern societies. The present study was conducted to explore
      probable issues which might lead to self-immolation in young Kurdish Iraqi women.
      Methods: The present qualitative study was conducted in Soran, Erbil Governorate
      in Iraq, and the surrounding villages of Soran District (March 2015 to May 2016).
      Using purposive sampling, we conducted 24 in-depth interviews with women who had
      done self-immolation. The obtained data were analyzed using conventional content
      analysis. Results: The analysis of the data obtained from the interviews led to
      the extraction of five categories which seems to be related to self-immolation
      attempts, including not having control over personal life, marital conflicts,
      seeking attention, instilling guilt in the family members, and resentment towards
      male dominant community. Conclusion: Self-immolation is a multidimensional
      phenomenon that has not come to exist overnight and is rooted in various factors
      that join to encourage self-immolation attempts by women in critical situations.
      Comprehensive preventive strategies, such as cultural changes, along with
      education are required to help lower the rate of self-immolation.

PMID- 29344537
TI  - The Relationship between Health Literacy and Health Promoting Behaviors in
      Patients with Type 2 Diabetes.
AB  - Background: Health promoting behaviors are known to be a key factor in managing
      type 2 diabetes and improving the quality of life in diabetic patients. However,
      there is little known about the factors influencing these behaviors in diabetic
      patients. This study aimed to find the relationship between the health literacy
      and health promoting behaviors in patients with type II diabetes. Methods: This
      correlational study was conducted from August to September 2016 on 175 eligible
      diabetic patients (20 to 65 year-old) who referred to the selected centers of
      diabetes control in Ahvaz City. Patients were chosen using convenience non
      probable sampling. Data were collected by diabetic patients' health promoting
      behaviors' questionnaire and health literacy questionnaire. Data were analyzed
      using SPSS 22, descriptive statistics and Pearson's correlation coefficient.
      Result: The mean scores for health promoting behaviors and health literacy were
      determined 100.45+/-19.82 and 76.14+/-15.26, respectively. The highest and lowest
      scores in health promoting behaviors belonged to nutrition (26.11+/-6.85) and
      physical activity (6.70+/-2.75), respectively. There was a significant
      relationship between all dimensions of health promoting behaviors and health
      literacy (P<0.05). Conclusion: Since health literacy has a positive relationship
      with health promoting behaviors in diabetic patients, health care providers need
      to concentrate on increasing the health literacy of their patients rather than
      solely concentrating on increasing their knowledge, thereby facilitating the
      development of health promoting behaviors in patients.

PMID- 29344538
TI  - Lived Experiences of Mothers with Diabetic Children from the Transfer of Caring
      Role.
AB  - Background: Following the confirmed type 1 diabetes in children and their
      discharge from the hospital, the care responsibilities are transferred from
      nurses to mothers. These mothers are faced with many challenges to play this
      caring role. The aim of this study was to explore the experiences of the diabetic
      children's mothers from the transfer of caring role. Methods: In 2016, semi
      structured interviews with Eleven Iranian mothers of children (aged<=14 year)
      with type 1 diabetes were conducted. Data were analyzed using Colizzi's
      phenomenological method. Results: The following themes emerged in this study:
      'Facing the care management challenges,' 'care in the shadow of concern', and
      'hard life in the impasse of diabetes'. Conclusion: The mothers of children with
      type 1 diabetes, who undertake the caring role that has been transferred to them
      by healthcare providers, are faced with many challenges. They feel a lot of
      concerns and experience a hard life. Thus, understanding the experiences of these
      mothers by the health professionals, to improve the quality of care, is
      necessary.

PMID- 29344539
TI  - Agreement between Heart Failure Patients and Their Primary Caregivers on Symptom
      Assessment.
AB  - Background: To decrease the readmission rate of heart failure (HF) patients,
      patients and their caregivers (CGs) should participate in symptoms assessment.
      This study aimed to assess the agreement between HF patients and their CGs on
      symptoms assessment. Methods: Using a correlational design, 100 HF patients with
      their CGs (100 dyads) were recruited from Department of Cardiology, Iranshahr,
      during August-December 2014. Data were collected using modified Heart Failure
      Symptom Survey (HFSS).Pearson and intra-class correlation coefficients (ICC) were
      used to analyze the degree of agreement within HF dyads, using SPSS16. The level
      of significance was set at 0.05. Results: The most frequent and severe symptom
      assessed equally by partners was shortness of breath (SOB). Dyads had a good
      agreement on assessment of extremity swelling (r=0.87, P<=0.01, ICC=0.861 CI:
      0.798-0.901), SOB at rest (r=0.83, P<=0.01, ICC=0.775, CI: 0.680-0.845), SOB with
      activity (r=0.81, P<=0.01, ICC=0.795 CI: 0.711-0.858), and feeling depressed
      (r=0.77, P<=0.01, ICC=0.769, CI: 0.675-0.838). 28.6% of HF dyad had a good, 50%
      had a moderate, and 21.4 % had a poor agreement in assessment of HF symptoms.
      Conclusion: Most of the HF dyad members did not agree with each other on the
      assessment of symptoms. Knowledge, skills and ability of each dyad in HF symptoms
      assessment should be included in the patients' discharge planning and nurses must
      modify their misunderstanding or inability.

PMID- 29344540
TI  - Standing Height as a Prevention Measure for Overuse Injuries of the Back in
      Alpine Ski Racing: A Kinematic and Kinetic Study of Giant Slalom.
AB  - Background: In alpine ski racing, typical loading patterns of the back include a
      combined occurrence of spinal bending, torsion, and high peak loads. These
      factors are known to be associated with high spinal disc loading and have been
      suggested to be attributable to different types of spine deterioration. However,
      little is known about the effect of standing height (ie, the distance between the
      bottom of the running surface of the ski and the ski boot sole) on the
      aforementioned back loading patterns. Purpose: To investigate the effect of
      reduced standing height on the skier's overall trunk kinematics and the acting
      ground-reaction forces in giant slalom (GS) from an overuse injury prevention
      perspective. Study Design: Controlled laboratory study. Methods: Seven European
      Cup-level athletes skied a total of 224 GS turns with 2 different pairs of skis
      varying in standing height. Their overall trunk movement (frontal bending,
      lateral bending, and torsion angles) was measured based on 2 inertial measurement
      units located at the sacrum and sternum. Pressure insoles were used to determine
      the total ground-reaction force. Results: During the turn phase in which the
      greatest spinal disc loading is expected to occur, significantly lower total
      ground-reaction forces were observed for skis with a decreased standing height.
      Simultaneously, the skier's overall trunk movement (ie, frontal bending, lateral
      bending, and torsion angles) remained unwaveringly high. Conclusion: Standing
      height is a reasonable measure to reduce the skier's overall back loading in GS.
      Yet, when compared with the effects achievable by increased gate offsets in
      slalom, for instance, the preventative benefits of decreased standing height seem
      to be rather small. Clinical Relevance: To reduce the magnitude of overall back
      loading in GS and to prevent overuse injuries of the back, decreasing standing
      height might be an efficient approach. Nevertheless, the clinical relevance of
      the current findings, as well as the effectiveness of the measure "reduced
      standing height," must be verified by epidemiological studies before its
      preventative potential can be judged as conclusive.

PMID- 29344541
TI  - Bony Maturity of the Tibial Tuberosity With Regard to Age and Sex and Its
      Relationship to Pathogenesis of Osgood-Schlatter Disease: An Ultrasonographic
      Study.
AB  - Background: Although tensile force on an immature tibial tuberosity is considered
      the main cause of Osgood-Schlatter disease (OSD), the relationship between bony
      maturity and the pathogenesis of OSD remains obscure. Purpose: To survey the bone
      maturation process of the tibial tuberosity by age and sex and clarify its
      relationship to OSD. Study Design: Cross-sectional study; Level of evidence, 3.
      Methods: A total of 731 Japanese basketball players aged 6 to 14 years were
      enrolled in this study. Ultrasonographic examination was performed in all
      participants (1462 knees) to evaluate the bony maturity of the tibial tuberosity
      by use of the Ehrenborg classification. The age- and sex-specific prevalence of
      each stage was investigated, and the prevalence of symptomatic OSD and its
      relationship with bony maturity were also assessed. Results: The process of bone
      maturation occurred 1 to 2 years earlier in female participants compared with
      male participants. Among female participants, 59.2% were already at the
      epiphyseal stage (stage E) by 10 years of age, and 47.4% were skeletally mature
      by 14 years. Among male participants, conversely, only 8.0% were at stage E by 10
      years of age, and only 13.8% were skeletally mature by 14 years. The overall
      prevalence of symptomatic OSD was 6.8% (males, 6.4%; females, 7.2%), and the
      onset was 1 year earlier in the female participants. The prevalence of
      symptomatic OSD tended to increase with age and bony maturity, significantly
      increasing from the cartilaginous stage (stage C) to the apophyseal stage (stage
      A) (odds ratio, 9.48) and from stage A to stage E (odds ratio, 2.22). Conclusion:
      The tibial tuberosity matures earlier in female participants. The risk of OSD is
      greater in stage A than stage C and in stage E than stage A. The risk of OSD
      increases with age in males but not in females.

PMID- 29344542
TI  - Ruxolitinib for essential thrombocythemia?

PMID- 29344543
TI  - Targeting H(i)ck education for cancer therapy?

PMID- 29344544
TI  - Multiple pro-tumor roles for protein acyltransferase DHHC3.

PMID- 29344545
TI  - In vivo pieces of the PP2A onco-puzzle fallen into place.

PMID- 29344546
TI  - RUNX3 loss turns on the dark side of TGF-beta signaling.

PMID- 29344547
TI  - Mesenchymal stem cells in breast cancer: response to chemical and mechanical
      stimuli.

PMID- 29344548
TI  - Recombinant ADAMTS 13 in thrombotic thrombocytopenic purpura.

PMID- 29344549
TI  - E-cadherin and K-ras: implications of a newly developed model of gastric cancer.

PMID- 29344550
TI  - Neutrophils and anti-cancer immunity: a paradigm shift in cancer immunotherapy.

PMID- 29344551
TI  - Cell-autonomous and non-autonomous functions of S100A4 in regulating stemness,
      mesenchymal transition, and metastasis.

PMID- 29344552
TI  - Collagen and Calcium Binding EGF Domains 1 (CCBE1) in cancer - a new role past
      lymphatics?

PMID- 29344553
TI  - Reprogramming patient-derived tumor cells generates model cell lines for tuberous
      sclerosis-associated lymphangioleiomyomatosis.

PMID- 29344554
TI  - Pulling the plug - halting cancer's theft of mitochondria.

PMID- 29344555
TI  - Destroying the androgen receptor (AR)-potential strategy to treat advanced
      prostate cancer.

PMID- 29344556
TI  - Extracellular matrix composition modulates angiosarcoma cell attachment and
      proliferation.
AB  - Angiosarcoma is a rare and generally fatal tumor composed of aberrant cells of
      endothelial origin. Because of its infrequency in humans, very little is known
      about the growth requirements of this vascular sarcoma. Unlike the rapidly
      proliferating solid tumors from which they are isolated from, many of the
      established angiosarcoma cell lines exhibit less than robust growth in culture
      and often fail to form tumors in xenograft models. In order to better understand
      angiosarcoma in vitro growth conditions, we focused on a singular aspect of their
      culture-adhesion to the extracellular matrix-in order to identify attachment
      substrates that may facilitate and/or enhance their growth in tissue culture. Our
      data indicates that the extracellular matrix of angiosarcomas contains similar
      protein compositions to that of non-diseased endothelial cells. Moreover,
      angiosarcoma cell lines exhibited strong attachment preference to substrates such
      as collagen I or fibronectin, and less preference to collagen IV, laminin, or
      tropoelastin. Growth on preferred extracellular matrix substrates promoted
      mitogenic signaling and increased proliferation of angiosarcoma cell lines. These
      findings provide insight that may lead to more successful in vitro growth of
      angiosarcoma cell lines.

PMID- 29344557
TI  - In colonic rho0 (rho0) cells reduced mitochondrial function mediates
      transcriptomic alterations associated with cancer.
AB  - Background: Mitochondrial reprogramming has emerged as a hallmark of cancer
      pathobiology. Although it is believed this reprogramming is essential for cancer
      cells to thrive, how it supports cancer pathobiology is unclear. We previously
      generated colonic rho0 (rho0) cells with reduced mitochondrial energy function
      and acquired their transcriptional signature. Here, we utilized a bioinformatics
      approach to identify their changes linked to cancer pathobiology. Methods: Human
      colon cancer HCT116 cells, control and rho0, were used for qPCR. Bioinformatics
      analysis: GeneCards, Kaplan-Meier Survival, GENT, cBioPortal. Results: The
      colonic rho0 transcriptome was linked with proliferation, DNA replication,
      survival, tumor morphology, and cancer. Among differentially expressed
      transcripts, 281 were regulators or biomarkers of human colon cancer especially
      those with inflammatory microsatellite instability (MSI). We identified and
      validated novel transcripts in rho0 cells with altered expression in human colon
      cancer. Among them DGK1, HTR7, FLRT3, and ZBTB18 co-occurred with established
      regulators of human colon cancer pathobiology. Also, increased levels of DGKI,
      FLRT3, ZBTB18, and YPEL1 as well as decreased levels of HTR7, and CALML6 were
      linked to substantially poorer patient survival. Conclusion: We identified
      established and novel regulators in colon cancer pathobiology that are dependent
      on mitochondrial energy reprogramming and linked to poorer patient survival.

PMID- 29344558
TI  - Therapeutic potential of bleomycin plus suicide or interferon-beta gene transfer
      combination for spontaneous feline and canine melanoma.
AB  - We originated and characterized melanoma cell lines derived from tumors of two
      feline and two canine veterinary patients. These lines reestablished the
      morphology, physiology and cell heterogeneity of their respective parental
      tumors. We evaluated the cytotoxicity of bleomycin (BLM) alone, or combined with
      interferon-beta (IFN-beta) or HSVtk/GCV suicide gene (SG) lipofection on these
      cells. Although the four animals presented stage III disease (WHO system), SG
      treated feline tumors displayed stable disease in vivo, while the canine ones
      exhibited partial response. Their derived cell lines reflected this behavior.
      Feline were significantly more sensitive than canine cells to IFN-beta gene
      transfer. BLM improved the antitumor effects of both genes. The higher levels of
      reactive oxygen species (ROS) significantly correlated with membrane and DNA
      damages, emphasizing ROS intervention in apoptotic and necrotic cell death. After
      3 days of BLM alone or combined with gene treatments, the colony forming capacity
      of two canine and one feline treatments survivor cells almost disappeared. Taken
      together, these results suggest that the treatments eradicated tumor initiating
      cells and support the clinical potential of the tested combinations.

PMID- 29344559
TI  - Infant Feeding Regimens and Gastrointestinal Tolerance: A Multicenter,
      Prospective, Observational Cohort Study in China.
AB  - To study feeding tolerance in infants fed formula with increased sn-2 palmitate
      and oligofructose (sn-2+OF) in a real-world setting, healthy Chinese infants were
      enrolled in this 48-day observational study on their current feeding regimens:
      exclusively breastfed (BF; n = 147), exclusively sn-2+OF formula-fed (FF; n =
      150), or mixed-fed with breast milk and sn-2+OF formula (MF; n = 163). Throughout
      the study, incidence (90% confidence interval) of hard stools was <=2.1% (0.0
      5.3) in FF and 0.8% (0.0-3.5) in MF, with no hard stools in BF. Incidence of
      watery stools was <=5.0% (1.0-9.2) in FF and >=5.1% (2.4-9.3) in MF and BF.
      Gastrointestinal tolerance scores, although low in all groups (lower scores
      indicating better tolerance), were slightly higher (P >= .03) in FF (17.5 +/-
      4.8) and MF (18.2 +/- 5.0) versus BF (16.3 +/- 3.2) at mid-study; this difference
      disappeared at study end. Overall, low incidences of hard and watery stools and
      good feeding tolerance were observed in infants fed sn-2+OF formula.

PMID- 29344560
TI  - Nonbilious Vomiting in a 4-Week-Old Male: A Case Report and Review of the
      Literature.

PMID- 29344561
TI  - Self-expandable metal stent placement in a child for treatment of achalasia after
      failed Heller myotomy.
AB  - Background and study aims  Childhood achalasia treatment remains inconclusive.
      What is next after myotomy failure? Repeated pneumatic-dilation put patients at
      greater risk of perforation with possible symptom recurrence. We report on a 12
      year-old patient with a 1-year history of achalasia whom underwent Heller myotomy
      with fundoplication and recurred with symptoms 1 week after surgery. Pneumatic
      dilatation was considered but not done because of the risk of esophageal
      perforation. The decision was made to place a fully covered self-expanding
      metallic stent (FC-SEMS) for 3 months, which resolved the stenosis as confirmed
      by esophagram. The patient has remained asymptomatic since the procedure was
      performed 2 years ago. FC-SEMS is an alternative for treatment of refractory
      achalasia in children who do not respond to conventional treatment.

PMID- 29344562
TI  - Endoscopic ultrasound-guided choledochoduodenostomy using partially-covered self
      expandable metal stent in patients with malignant distal biliary obstruction and
      unsuccessful ERCP.
AB  - Background and study aims : Endoscopic ultrasound-guided choledochoduodenostomy
      (EUS-CDS) is an alternative to percutaneous transhepatic biliary drainage (PTBD)
      for patients with malignant distal biliary obstruction in whom ERCP has failed.
      We studied technical success, clinical success, stent patency rate and occurrence
      of adverse events in patients undergoing EUS-CDS with partially-covered self
      expanding metal stent (PCSEMS). Patients and methods : Medical records of
      consecutive patients with unresectable malignant distal biliary obstruction
      requiring biliary drainage who underwent EUS-CDS because of failure of attempt at
      ERCP were reviewed. EUS-CDS was done using 6-cm, PCSEMS (Wallflex, Boston
      Scientific). Technical success, clinical success (more than 50 % reduction in
      total bilirubin at 2 weeks post-procedure), stent patency rate and adverse events
      (AEs) were assessed. Patients were followed up for 3 months post-procedure.
      Results : Between January 2015 and December 2016, 30 patients underwent EUS-CDS,
      including 20 (67 %) with failed biliary cannulation and 10 (33 %) with duodenal
      stenosis. Technical success was achieved in 28 patients, all of whom also had
      clinical success. Median total serum bilirubin decreased from 20 mg/dL to 5 mg/dL
      at 2 weeks post-procedure. Three patients (10 %) had adverse events (bile leak,
      hemobilia, stent block in one patient each; no stent migration); none of these
      adverse events was major and all were managed successfully. There were no
      procedure-related deaths. Five patients died of disease progression in the 3
      month period post-procedure, and the 3-month dysfunction-free stent patency rate
      was 83 %. Conclusion : EUS-CDS with a PCSEMS has a high technical and clinical
      success. Adverse events were infrequent, minor and could be managed easily.

PMID- 29344563
TI  - The use of fully-covered self-expanding metallic stents for intraprocedural
      management of post-sphincterotomy perforations: a single-center study (with
      video).
AB  - Background and study aims : Management of post-sphincterotomy perforations is
      variable, with some patients managed conservatively and other requiring surgery.
      Fully-covered self-expanding metal stents (FCSEMs) have been used in the past,
      but data is limited. The aim of this study was to report the clinical
      characteristics and outcomes following placement of anchored FCSEMSs for the
      immediate management of post-sphincterotomy perforation. Patients and methods :
      All patients undergoing an ERCP procedure between June 2011 and December 2015 at
      our institution were reviewed for post-sphincterotomy perforation. All intra
      procedurally recognized perforations underwent placement of FCSEMs with flexible
      anchoring fins and were included in this study. Data extracted included patient
      demographics, indication, peri-procedural details, clinical course and long-term
      outcome following anchored FCSEMS placement. Results : A total of 15 patients (12
      females, median age-66 years) with post-sphincterotomy perforation were included.
      Major indications included choledocholithiasis in 9 (60 %), and 5 (33.3 %)
      patients had intra-ampullary or periampullary diverticula. All patients underwent
      placement of FCSEMS without any complication and had immediate resolution of
      perforation as evidenced by decrease in fluoroscopic gas and lack of contrast
      extravasation. None of the patients became symptomatic or needed surgery with a
      median 2 days of hospitalization following the procedure. Stents were removed
      after a median of 30.5 days and no complications were noted during follow-up
      after stent removal. Conclusions : Anchored FCSEMs are safe and effective for
      management of intra-procedurally recognized post-sphincterotomy perforations and
      obviates need for surgery.

PMID- 29344564
TI  - Endoscopic ultrasound guided needle-based confocal laser endomicroscopy in solid
      pancreatic masses - a prospective validation study.
AB  - Background and study aims:  Endoscopic ultrasound fine-needle aspiration (EUS
      FNA) is a keystone in diagnosing and staging of pancreatic masses. Recently, a
      microfiber that can pass through a 19-gauge needle has been introduced for
      confocal laser endomicroscopy (nCLE). The aims of this study were to evaluate the
      diagnostic value and the reproducibility of nCLE criteria for solid malignant
      lesions. Patients and methods:  This prospective dual-center study included
      patients with pancreatic masses suspicious of malignancy referred for EUS-FNA.
      Endomicroscopic imaging was performed under EUS-guidance until organ-specific
      structures were obtained. Afterwards, standard cytology was obtained and patients
      were followed for up to 12 months. All nCLE parameters included in former studies
      were correlated with the final diagnosis (dark lobular structures/normal acinar
      cells, dark cell aggregates > 40 um, dilated irregular vessels with fluorescein
      leakage, fine white fibrous bands, small black cell movements, pseudoglandular
      structures). Finally, three CLE novices and three CLE experts assessed the
      unedited movies from all patients. Results:  Twenty-eight patients were enrolled
      in the study. A final diagnosis was obtained in 24 patients (86 %). One patient
      (3 %) died before a diagnosis was obtained, while 3 were lost to follow-up (11
      %). In 18/24 patients (74 %) the diagnosis was malignant. The mean sensitivity,
      specificity, and accuracy for the nCLE parameters ranged from 19 - 93 %, 0 - 56
      %, 26 - 69 %, respectively. The inter-observer values ranged from kappa = 0.20 -
      0.41 for novices and kappa = -0.02 - 0.38 for experts. Conclusions:  The
      diagnostic value of nCLE in solid pancreatic masses is questionable and the inter
      observer agreement for both novices and CLE experts appears limited.

PMID- 29344565
TI  - A novel method of endoscopic-assisted esophageal clearance in advanced achalasia.
AB  - Background and study aims : In order to perform peroral endoscopic myotomy (POEM)
      safely, retained liquid and food debris must be removed before the procedure is
      started. We developed a novel technique using a super-slim gastroscope, and a
      gastric tube to remove retained food debris in achalasia patients. In this study,
      the safety and efficacy of this novel technique were investigated. Patients and
      methods : Eleven patients with achalasia were enrolled in this study and
      underwent this novel method for esophageal clearance. Results:  All patients had
      complete clearance of the retained food debris using this method. The median
      procedure time (range) was 13 (6 - 30) minutes. There were no serious adverse
      events (AEs) and one minor AE of mucosal erythema due to mucosal suctioning.
      Conclusion:  This novel method for esophageal clearance is safe and effective in
      achalasia patients with large amounts of retained food debris.

PMID- 29344567
TI  - Response to letter to the editor - "Training in ERCP: a multifaceted enterprise
      now more than ever".

PMID- 29344566
TI  - Training in ERCP: a multifaceted enterprise now more than ever.

PMID- 29344568
TI  - Non-surgical management of Boerhaave's syndrome: a case series study and review
      of the literature.
AB  - Background and study aims:  Boerhaave's syndrome (BS) is a life-threatening
      condition with morbidity and mortality rates as high as 50 % in some reports.
      Until recently, surgical intervention has been the mainstay of management plans.
      With advances in therapeutic endoscopy, however, there has been increasing
      interest in non-surgical options including endoscopic esophageal stenting.
      Patients and methods:  We reviewed the medical records of all patients diagnosed
      with BS and managed with endoscopic interventions between November 2011 and
      November 2016. The following variables were collected: patient demographics,
      clinical presentations, locations of esophageal perforation, primary
      interventions, complications, and outcomes. Results:  Six patients were found to
      be diagnosed with BS during the study period. The median age at presentation was
      55. There were 4 males and 2 females. The most common site of perforation was in
      the distal esophagus. The most common presenting symptom was chest pain (67 %)
      following an episode of vomiting or retching. Four patients (66.7 %) developed
      septic shock. Endoscopic treatment with a fully covered esophageal stent was the
      primary intervention in all patients (100 %). Interventional radiology was
      consulted in all cases for fluid drainage and chest tube placements. Clinical
      resolution of the BS was achieved in all patients (100 %) without any subsequent
      surgical interventions. There were no deaths within the study group, and the
      average follow-up duration was 2 years. Conclusion:  Endoscopic treatment seems
      to be an effective management strategy in patients with BS. We also noted
      satisfactory results in patients presenting with sepsis, presumably due to
      urgent, interventional radiology-guided fluid drainage.

PMID- 29344569
TI  - Endoscopic full-thickness resection with an over-the-scope clip device (FTRD) in
      the colorectum: results from a university tertiary referral center.
AB  - Background and study aims:  The full-thickness resection device (FTRD) represents
      a novel endoscopic treatment method for lesions unresectable with conventional
      endoscopic techniques. The overall aim of this study was to evaluate technical
      success and in toto resection rates, recurrence rates, as well as immediate or
      late complications in patients who underwent polyp removal with the FTRD.
      Patients and methods:  Data from a prospectively collected database of 12
      patients who underwent 13 over-the-scope clip-based full-thickness resections
      between June 2015 and June 2017 were analyzed. Follow-up endoscopy was performed
      in 11 out of 12 patients. Results:  13 full-thickness resections were performed
      in 7 males and 5 females (mean age 64.3 +/- 6.3 years). Mean size of the lesions
      removed with FTRD was 17 +/- 4 mm. Location was rectum (n = 6), cecum (n = 2),
      ascending colon (n = 2), left flexure (n = 1) and right flexure (n = 2). Mean
      procedure time was 68 +/- 35 minutes and mean hospital stay was 2.5 +/- 1.2 days.
      2 patients developed post-polypectomy syndrome, which resolved after conservative
      treatment. No perforations and no immediate surgical revision were needed.
      Histology of the 13 lesions removed with FTRD showed 5 adenomas with low grade
      intraepithelial neoplasia (IEN), 4 high grade IEN, 1 fibrosis, 1 fibrosis without
      dysplasia and 2 adenocarcinomas. Technical success was achieved in all procedures
      (13/13, 100 %). R0 resection was achieved in 10/12 patients (83.3 %). 2 patients
      underwent surgery because of recurrence or not evaluable margins. In 1 patient no
      residual malignancy was proven in histological examination, in the other patient
      residual low grade IEN adenoma. Conclusion:  FTRD is a minimally invasive
      approach with good success rate of complete resection and minimal side effects.

PMID- 29344570
TI  - Use of anticoagulant or antiplatelet agents is not related to epistaxis in
      patients undergoing transnasal endoscopy.
AB  - Background and study aims : Unsedated transnasal endoscopy (uTNE) has become
      accepted as a safe and tolerable method for upper gastrointestinal tact
      examinations. Epistaxis is 1 of the major complications of TNE, though its risk
      factors have not been elucidated. Generally, patients administered an
      anticoagulant or antiplatelet drug are considered to have an increased risk of
      epistaxis during TNE. Here, we investigated risk factors of epistaxis in patients
      undergoing uTNE, with focus on those who received antithrombotic agents. Patients
      and methods : We enrolled 6860 patients (average age 55.6 +/- 12.97 years; 3405
      males, 3455 females) who underwent uTNE and received the same preparations for
      the procedure. Epistaxis was evaluated using endoscopic images obtained while
      withdrawing the scope through the nostril. We also noted current use of
      medications including anticoagulant or antiplatelet agents prior to the
      endoscopic examination. Results : Epistaxis occurred in 3.6 % of the enrolled
      patients (245/6860), and that rate was significantly higher in younger patients
      (average age 49.31 +/- 11.8 years for epistaxis group vs. 55.83 +/- 13.0 years
      for no epistaxis group, P  < 0.01) as well as females (4.78 % vs. 2.35 %, P  <
      0.01). The odds ratio for occurrence of epistaxis was 2.31 (95 %CI: 1.746 -
      3.167) in the younger patients and 2.02 (95 % CI: 1.542 - 2.659) in females. In
      contrast, there was no significant difference for rate of epistaxis between
      patients with and without treatment with an antithrombotic agent (3.0 % vs. 3.6
      %). Conclusions : The rate of epistaxis was higher in younger and female
      patients. Importantly, that rate was not significantly increased in patients who
      were administered an antithrombotic agent.

PMID- 29344571
TI  - Underwater endoscopic mucosal resection: a new endoscopic method for resection of
      rectal neuroendocrine tumor grade 1 (carcinoid) <= 10 mm in diameter.
AB  - Background and study aims  Rectal neuroendocrine tumors grade 1 (NET G1;
      carcinoid) <= 10 mm in diameter often extend into the submucosa, making their
      complete histological resection difficult using endoscopic techniques. Endoscopic
      submucosal resection with a ligation device (ESMR-L) and endoscopic submucosal
      dissection (ESD) are commonly used to overcome these difficulties. We also
      previously reported that underwater endoscopic mucosal resection (UEMR) could
      facilitate resection of rectal NET G1. This study aimed to evaluate the safety
      and efficacy of UEMR for removing rectal NET G1 <= 10 mm in diameter. 6
      consecutive patients with rectal NET G1 <= 10 mm in diameter underwent UEMR at
      our hospital. The rate of en bloc resection was 100 %, and the rate of R0
      resection was 83 %. The median procedure time was 8 min (range 5 - 12 min). No
      perforations or delayed bleeding occurred in this study. In conclusion, UEMR
      allows the safe and reliable resection of rectal NET G1 <= 10 mm in diameter with
      comparable results to ESMR-L or ESD, including high en bloc and R0 resection
      rates with no increase in significant adverse events. A multicenter trial is
      required to confirm the validity of the present results.

PMID- 29344572
TI  - Expert-led didactic versus self-directed audiovisual training of confocal laser
      endomicroscopy in evaluation of mucosal barrier defects.
AB  - Background and study aims:  Confocal laser endomicroscopy (CLE) allows mucosal
      barrier defects along the intestinal epithelium to be visualized in vivo during
      endoscopy. Training in CLE interpretation can be achieved didactically or through
      self-directed learning. This study aimed to compare the effectiveness of expert
      led didactic with self-directed audiovisual teaching for training inexperienced
      analysts on how to recognize mucosal barrier defects on endoscope-based CLE
      (eCLE). Materials and methods:  This randomized controlled study involved trainee
      analysts who were taught how to recognize mucosal barrier defects on eCLE either
      didactically or through an audiovisual clip. After being trained, they evaluated
      6 sets of 30 images. Image evaluation required the trainees to determine whether
      specific features of barrier dysfunction were present or not. Trainees in the
      didactic group engaged in peer discussion and received feedback after each set
      while this did not happen in the self-directed group. Accuracy, sensitivity, and
      specificity of both groups were compared. Results : Trainees in the didactic
      group achieved a higher overall accuracy (87.5 % vs 85.0 %, P  = 0.002) and
      sensitivity (84.5 % vs 80.4 %, P  = 0.002) compared to trainees in the self
      directed group. Interobserver agreement was higher in the didactic group (k =
      0.686, 95 % CI 0.680 - 0.691, P  < 0.001) than in the self-directed group (k =
      0.566, 95 % CI 0.559 - 0.573, P  < 0.001). Confidence (OR 6.48, 95 % CI 5.35 -
      7.84, P  < 0.001) and good image quality (OR 2.58, 95 % CI 2.17 - 2.82, P  <
      0.001) were positive predictors of accuracy. Conclusion:  Expert-led didactic
      training is more effective than self-directed audiovisual training for teaching
      inexperienced analysts how to recognize mucosal barrier defects on eCLE.

PMID- 29344573
TI  - Development of an external-to-internal convertible endoscopic biliary drainage
      device - a preliminary prospective feasibility study.
AB  - Background and study aims:  Endoscopic nasobiliary drainage (ENBD) for a
      malignant stricture in the bile duct has some advantages over endoscopic biliary
      stenting (EBS). However, ENBD may cause nasopharyngeal discomfort. We developed
      an external-to-internal convertible endoscopic biliary drainage (ETI-EBD) device
      that enables both internal and external drainage to occur during a single
      endoscopy. Patients and methods : This device consists of three parts, comprising
      a 5-Fr ENBD tube (250 cm) (ENBD-t), an 8.5-Fr EBS tube (7 cm) (EBS-t), and an 8
      Fr pusher tube for EBS (230 cm) (P-t). The EBS-t is mounted over the ENBD-t at
      the distal end of the ENBD-t. The P-t is also placed over the ENBD-t. After an
      endoscopic sphincterotomy, the EBS-t of the device is inserted into the papilla,
      then the duodenal endoscope is withdrawn, leaving the device in place. After
      ENBD, only the ENBD-t was withdrawn from the P-t. At this point, the EBS-t was
      isolated and left without endoscopy or radiography. Results : ETI-EBD was
      successfully placed in all consecutive 21 patients (100 %). The release of EBS-t
      from ENBD-t wit was successfully completed in 19 patients (90.5 %). There were 4
      patients with kink of P-t when exchanging this device from the mouth to the nose.
      It was difficult for 2 patients to withdraw the ENBD-t because of poor
      lubrication performance. There were no significant complications associated with
      the use of the device. Conclusion : This device allows for both external and
      internal biliary drainage with a single endoscopy.

PMID- 29344574
TI  - Observation of spin-orbit magnetoresistance in metallic thin films on magnetic
      insulators.
AB  - A magnetoresistance (MR) effect induced by the Rashba spin-orbit interaction was
      predicted, but not yet observed, in bilayers consisting of normal metal and
      ferromagnetic insulator. We present an experimental observation of this new type
      of spin-orbit MR (SOMR) effect in the Cu[Pt]/Y3Fe5O12 (YIG) bilayer structure,
      where the Cu/YIG interface is decorated with nanosize Pt islands. This new MR is
      apparently not caused by the bulk spin-orbit interaction because of the
      negligible spin-orbit interaction in Cu and the discontinuity of the Pt islands.
      This SOMR disappears when the Pt islands are absent or located away from the
      Cu/YIG interface; therefore, we can unambiguously ascribe it to the Rashba spin
      orbit interaction at the interface enhanced by the Pt decoration. The numerical
      Boltzmann simulations are consistent with the experimental SOMR results in the
      angular dependence of magnetic field and the Cu thickness dependence. Our finding
      demonstrates the realization of the spin manipulation by interface engineering.

PMID- 29344575
TI  - Mammary Myofibroblastoma in a Transgender Patient on Feminizing Hormones:
      Literature Review and Case Report.
AB  - Purpose: Defining the risk of neoplasia associated with gender-affirming hormone
      therapy (GAHT) is a priority for transgender medical research. The purposes of
      this article are to present a unique case of breast neoplasia in a transgender
      individual and to review the existing evidence base on GAHT as a potential risk
      for breast pathology. Methods: We present the case of a 76-year-old transgender
      patient who developed an estrogen receptor-positive mammary myofibroblastoma
      (MFB) after 13 months of treatment on feminizing hormones. To our knowledge, this
      is the first reported case of MFB occurring in a transgender individual. A
      literature review was conducted to identify all reported cases of breast
      neoplasia among transgender individuals receiving feminizing GAHT. Information
      was abstracted from each of the included cases to describe the existing body of
      literature and to compare published cases to the case reported in this study.
      Results: We identified a total of 19 malignant and 3 benign cases of breast
      neoplasia among transgender women. Ours is the first reported case of MFB in a
      transgender individual receiving feminizing hormones and the first reported case
      of breast neoplasia associated with GAHT administered via the estradiol patch.
      Conclusion: This case reinforces the need for additional reporting of breast
      neoplasia presenting in transgender individuals treated with feminizing hormones.
      The relationship between estrogen exposure and breast neoplasia in the
      transgender population remains poorly defined, and additional research is needed
      to define risks and inform clinical practice.

PMID- 29344576
TI  - Clinical Exposure to Transgender Medicine Improves Students' Preparedness Above
      Levels Seen with Didactic Teaching Alone: A Key Addition to the Boston University
      Model for Teaching Transgender Healthcare.
AB  - Purpose: Transgender individuals are medically underserved in the United States
      and face many documented disparities in care due to providers' lack of education,
      training, and comfort. We have previously demonstrated that specific transgender
      medicine content in a medical school curriculum increases students' willingness
      to treat transgender patients. However, we have also identified that those same
      students are less comfortable with transgender care relative to care for lesbian,
      gay, and bisexual patients. We aimed to demonstrate that clinical exposure to
      care for transgender patients would help close this gap. Methods: At Boston
      University School of Medicine, we piloted a transgender medicine elective where
      students rotate on services that provide clinical care for transgender
      individuals. Pre- and postsurveys were administered to students who participated
      in the elective. Results: After completing the elective, students who reported
      "high" comfort increased from 45% (9/20) to 80% (16/20) (p=0.04), and students
      who reported "high" knowledge regarding management of transgender patients
      increased from 0% (0/20) to 85% (17/20) (p<0.001). Conclusion: Although
      integrating evidence-based, transgender-specific content into medical curricula
      improves student knowledge and comfort with transgender medical care, gaps
      remain. Clinical exposure to transgender medicine during clinical years can
      contribute to closing that gap and improving access to care for transgender
      individuals.

PMID- 29344577
TI  - A Practical Approach to Using Trend Arrows on the Dexcom G5 CGM System for the
      Management of Adults With Diabetes.
AB  - After reviewing previously published methods, we developed a practical approach
      to adjusting insulin doses based on insulin sensitivity for adult patients with
      diabetes using rtCGM trend arrow data.

PMID- 29344578
TI  - A Practical Approach to Using Trend Arrows on the Dexcom G5 CGM System to Manage
      Children and Adolescents With Diabetes.
AB  - After assessing previously published methods, we developed a practical approach
      to adjusting insulin doses using rtCGM trend arrows in pediatric patients with
      diabetes.

PMID- 29344579
TI  - Prognostic significance of cytogenetic heterogeneity in patients with newly
      diagnosed multiple myeloma.
AB  - We investigated subclonal cytogenetic aberrations (CA) detected by interphase
      fluorescence in situ hybridization (iFISH) in patients with newly diagnosed
      multiple myeloma (MM) enrolled in the Haemato Oncology Foundation for Adults in
      the Netherlands (HOVON)-65/German-Speaking MM Group (GMMG)-HD4 phase 3 trial.
      Patients were either treated with 3 cycles of vincristine, Adriamycin, and
      dexamethasone or bortezomib, Adriamycin, and dexamethasone and then thalidomide
      or bortezomib maintenance after tandem autologous transplantation. Subclones were
      defined either by presence of different copy numbers of the same chromosome loci
      and/or CA present in at least 30% less and maximally 2/3 of cells compared with
      the main clone CA. Patients with subclones harbored more frequently high risk
      (31.0%) or hyperdiploid main clone aberrations (24.8%) than patients with
      t(11;14) in the main clone (10.1%). Gains and deletions of c-MYC were the only CA
      that occurred more frequently as subclone (8.1%/20.5%) than main clone
      (6.2%/3.9%, respectively). Treatment with bortezomib completely overcame the
      negative prognosis of high-risk CA in patients without subclones, but not in
      patients with additional subclonal CA. High-risk patients treated without
      bortezomib showed dismal outcome whether subclones were present or not.
      Cytogenetic heterogeneity defined by subclonal CA is of major prognostic
      significance in newly diagnosed MM patients treated with bortezomib within the
      HOVON-65/GMMG-HD4 trial.

PMID- 29344580
TI  - Successful treatment with fingolimod of graft-versus-host disease of the central
      nervous system.
AB  - Fingolimod could be efficient to treat GVHD of the central nervous system.Further
      research should explore the use of fingolimod and other sphingosine-1-phosphate
      receptor agonists to prevent or treat GVHD.

PMID- 29344581
TI  - Glycophorin-C sialylation regulates Lu/BCAM adhesive capacity during erythrocyte
      aging.
AB  - Lutheran/basal cell adhesion molecule (Lu/BCAM) is a transmembrane adhesion
      molecule expressed by erythrocytes and endothelial cells that can interact with
      the extracellular matrix protein laminin-alpha5. In sickle cell disease, Lu/BCAM
      is thought to contribute to adhesion of sickle erythrocytes to the vascular wall,
      especially during vaso-occlusive crises. On healthy erythrocytes however, its
      function is unclear. Here we report that Lu/BCAM is activated during erythrocyte
      aging. We show that Lu/BCAM-mediated binding to laminin-alpha5 is restricted by
      interacting, in cis, with glycophorin-C-derived sialic acid residues. Following
      loss of sialic acid during erythrocyte aging, Lu/BCAM is released from
      glycophorin-C and allowed to interact with sialic acid residues on laminin
      alpha5. Decreased glycophorin-C sialylation, as observed in individuals lacking
      exon 3 of glycophorin-C, the so-called Gerbich phenotype, was found to correlate
      with increased Lu/BCAM-dependent binding to laminin-alpha5. In addition, we
      identified the sialic acid-binding site within the third immunoglobulin-like
      domain within Lu/BCAM that accounts for the interaction with glycophorin-C and
      laminin-alpha5. Last, we present evidence that neuraminidase-expressing
      pathogens, such as Streptococcus pneumoniae, can similarly induce Lu/BCAM
      mediated binding to laminin-alpha5, by cleaving terminal sialic acid residues
      from the erythrocyte membrane. These results shed new light on the mechanisms
      contributing to increased adhesiveness of erythrocytes at the end of their
      lifespan, possibly facilitating their clearance. Furthermore, this work may
      contribute to understanding the pathology induced by neuraminidase-positive
      bacteria, because they are especially harmful to patients suffering from sickle
      cell disease and are associated with the occurrence of vaso-occlusive crises.

PMID- 29344582
TI  - Factor XIII in plasma, but not in platelets, mediates red blood cell retention in
      clots and venous thrombus size in mice.
AB  - The transglutaminase factor XIII (FXIII) stabilizes clots against mechanical and
      biochemical disruption and is essential for hemostasis. In vitro and in vivo
      models of venous thrombosis demonstrate that FXIII mediates clot size by
      promoting red blood cell (RBC) retention. However, the key source of FXIII and
      whether FXIII activity can be reduced to suppress thrombosis without imposing
      deleterious hemostatic consequences are 2 critical unresolved questions. FXIII is
      present in multiple compartments, including plasma (FXIIIplasma) as a
      heterotetramer of A2 and B2 subunits and platelets (FXIIIplt) as an A2 homodimer.
      We determined the role of the FXIII compartment and level in clot contraction,
      composition, and size in vitro and using in vivo models of hemostasis and venous
      thrombosis. Reducing overall FXIII levels decreased whole blood clot weight but
      did not alter thrombin generation or contraction of platelet-rich plasma clots.
      In reconstituted platelet-rich plasma and whole blood clot contraction assays,
      FXIIIplasma, but not FXIIIplt, produced high-molecular-weight fibrin crosslinks,
      promoted RBC retention, and increased clot weights. Genetically imposed reduction
      of FXIII delayed FXIII activation and fibrin crosslinking, suggesting FXIII
      levels mediate the kinetics of FXIII activation and activity and that the timing
      of these processes is a critical determinant of RBC retention during clot
      formation and contraction. A 50% reduction in FXIIIplasma produced significantly
      smaller venous thrombi but did not increase bleeding in tail transection or
      saphenous vein puncture models in vivo. Collectively, these findings suggest that
      partial FXIII reduction may be a therapeutic strategy for reducing venous
      thrombosis.

PMID- 29344584
TI  - Early and late outcomes after cord blood transplantation for pediatric patients
      with inherited leukodystrophies.
AB  - Leukodystrophies (LD) are devastating inherited disorders leading to rapid
      neurological deterioration and premature death. Hematopoietic stem cell
      transplantation (HSCT) can halt disease progression for selected LD. Cord blood
      is a common donor source for transplantation of these patients because it is
      rapidly available and can be used without full HLA matching. However, precise
      recommendations allowing care providers to identify patients who benefit from
      HSCT are lacking. In this study, we define risk factors and describe the early
      and late outcomes of 169 patients with globoid cell leukodystrophy, X-linked
      adrenoleukodystrophy, and metachromatic leukodystrophy undergoing cord blood
      transplantation (CBT) at an European Society for Blood and Marrow Transplantation
      center or at Duke University Medical Center from 1996 to 2013. Factors associated
      with higher overall survival (OS) included presymptomatic status (77% vs 49%; P =
      .006), well-matched (<=1 HLA mismatch) CB units (71% vs 54%; P = .009), and
      performance status (PS) of >80 vs <60 or 60 to 80 (69% vs 32% and 55%,
      respectively; P = .003). For patients with PS<=60 (n = 20) or 60 to 80 (n = 24)
      pre-CBT, only 4 (9%) showed improvement. Of the survivors with PS >80 pre-CBT,
      50% remained stable, 20% declined to 60 to 80, and 30% to <60. Overall, an
      encouraging OS was found for LD patients after CBT, especially for those who are
      presymptomatic before CBT and received adequately dosed grafts. Early
      identification and fast referral to a specialized center may lead to earlier
      treatment and, subsequently, to improved outcomes.

PMID- 29344583
TI  - Heterozygous RTEL1 variants in bone marrow failure and myeloid neoplasms.
AB  - Biallelic germline mutations in RTEL1 (regulator of telomere elongation helicase
      1) result in pathologic telomere erosion and cause dyskeratosis congenita.
      However, the role of RTEL1 mutations in other bone marrow failure (BMF) syndromes
      and myeloid neoplasms, and the contribution of monoallelic RTEL1 mutations to
      disease development are not well defined. We screened 516 patients for germline
      mutations in telomere-associated genes by next-generation sequencing in 2
      independent cohorts; one constituting unselected patients with idiopathic BMF,
      unexplained cytopenia, or myeloid neoplasms (n = 457) and a second cohort
      comprising selected patients on the basis of the suspicion of
      constitutional/familial BMF (n = 59). Twenty-three RTEL1 variants were identified
      in 27 unrelated patients from both cohorts: 7 variants were likely pathogenic, 13
      were of uncertain significance, and 3 were likely benign. Likely pathogenic RTEL1
      variants were identified in 9 unrelated patients (7 heterozygous and 2
      biallelic). Most patients were suspected to have constitutional BMF, which
      included aplastic anemia (AA), unexplained cytopenia, hypoplastic myelodysplastic
      syndrome, and macrocytosis with hypocellular bone marrow. In the other 18
      patients, RTEL1 variants were likely benign or of uncertain significance.
      Telomeres were short in 21 patients (78%), and 3' telomeric overhangs were
      significantly eroded in 4. In summary, heterozygous RTEL1 variants were
      associated with marrow failure, and telomere length measurement alone may not
      identify patients with telomere dysfunction carrying RTEL1 variants.
      Pathogenicity assessment of heterozygous RTEL1 variants relied on a combination
      of clinical, computational, and functional data required to avoid
      misinterpretation of common variants.

PMID- 29344585
TI  - Hereditary folate malabsorption due to a mutation in the external gate of the
      proton-coupled folate transporter SLC46A1.
AB  - Hereditary folate malabsorption (HFM) is an autosomal recessive disorder
      characterized by impaired intestinal folate absorption and impaired folate
      transport across the choroid plexus due to loss of function of the proton-coupled
      folate transporter (PCFT-SLC46A1). We report a novel mutation, causing HFM,
      affecting a residue located in the 11th transmembrane helix within the external
      gate. The mutant N411K-PCFT was stable, trafficked to the cell membrane, and had
      sufficient residual activity to characterize the transport defect and the
      structural requirements at this site for gate function. The influx Vmax of the
      N411K mutant was markedly decreased, as was the affinity for most, but not all,
      folate/antifolate substrates. The greatest loss of activity was for 5
      methyltetrahydrofolate. Substitutions with positive charged residues resulted in
      a loss of activity (arginine > lysine > histidine). Function was retained for the
      negative charged aspartate, but not the larger glutamate substitutions, whereas
      the bulky hydrophobic (leucine), or polar (glutamine) substitutions, were
      tolerated. Homology models of PCFT, in the inward and outward open conformations,
      based upon the mammalian Glut5 fructose transporter structures, localize Asn411
      protruding into the aqueous pathway. This is most prominent when the carrier is
      in the inward open conformation when the external gate is closed. Mutations at
      this site likely result in highly specific steric and electrostatic interactions
      between the Asn411-substituted, and other, residues in the gate region that
      impede carrier function. The substrate specificity of the N411K mutant may be due
      to alterations of substrate flows through the external gate, downstream
      allosteric alterations in the folate-binding pocket, or both.

PMID- 29344586
TI  - Systemic multilineage engraftment in mice after in utero transplantation with
      human hematopoietic stem cells.
AB  - IUHCT of human cord blood-derived CD34+ cells into fetal NSG mice results in
      systemic multilineage engraftment with human cells.Preconditioning with in utero
      injection of an anti-c-Kit receptor antibody (ACK2) results in an improved rate
      of engraftment.

PMID- 29344587
TI  - An exploratory study of red raspberry (Rubus idaeus L.) (poly)phenols/metabolites
      in human biological samples.
AB  - Red raspberry (Rubus idaeus L.) contains a variety of polyphenols including
      anthocyanins and ellagitannins. Red raspberry polyphenols absorbed in different
      forms (parent compounds, degradants or microbial metabolites) are subject to
      xenobiotic metabolism in the intestine, liver, and/or kidney, forming methylate,
      glucuronide, and sulfate conjugated metabolites. Upon acute exposure,
      (poly)phenol/metabolite presence in the blood depends mainly on intestinal
      absorption, enterohepatic circulation, and metabolism by resident microbiota.
      However, chronic exposure to red raspberry polyphenols may alter metabolite
      patterns depending on adaptions in the xenobiotic machinery and/or microbiota
      composition. Understanding the metabolic fate of these compounds and their
      composition in different biological specimens relative to the exposure time/dose
      will aid in designing future health benefit studies, including the mechanism of
      action studies. The present exploratory study applied ultra-high performance
      liquid chromatography (UHPLC) coupled with quadrupole time-of-flight (QTOF) and
      triple quadrupole (QQQ) mass spectrometries to characterize red raspberry
      polyphenols in fruit and then their appearance, including metabolites in human
      biological samples (plasma, urine and breast milk) after the chronic intake of
      red raspberries. The results suggested that the most abundant polyphenols in red
      raspberries included cyanidin 3-O-sophoroside, cyanidin 3-O-glucoside, sanguiin
      H6 and lambertianin C. Sixty-two (poly)phenolic compounds were tentatively
      identified in the plasma, urine and breast milk samples after the intake of red
      raspberries. In general, urine contained the highest content of phenolic
      metabolites; phase II metabolites, particularly sulfated conjugates, were mainly
      present in urine and breast milk, and breast milk contained fewer parent
      anthocyanins compared to urine and plasma.

PMID- 29344588
TI  - A helical chain-like organic-inorganic hybrid arsenotungstate with color-tunable
      photoluminescence.
AB  - A 1-D infinite helical chain-like organic-inorganic hybrid arsenotungstate
      Na4H8[{Pr(H2O)2}2{As2W19O68}{WO2(mal)}2].24H2O (mal = malate) (1) was prepared,
      which was characterized by elemental analyses, thermogravimetric (TG) analyses,
      IR spectroscopy, powder X-ray diffraction (PXRD) and X-ray single-crystal
      diffraction. Structural characterization revealed that 1 comprises the organo
      functionalized [{As2W19O68}{WO2(mal)}2]18- polyanions hinged together by the Pr3+
      ions forming a 1-D infinite helical chain-like architecture. The malate ligand
      may play a vital role to stabilize the structure of 1 by the formation of the
      five-membered W-O-C-C-O chelate ring. Solid state photoluminescence reveals that
      1 features excitation wavelength-dependent emission properties, achieving a
      reversible emission color switching simply via changing the excitation
      wavelength. Time-resolved emission spectroscopy (TRES) indicates that the
      photoexcitation O -> M ligand to metal charge transfer (LMCT) of arsenotungstate
      fragments can sensitize the Pr3+ ions through intramolecular energy transitions
      in 1.

PMID- 29344589
TI  - Magnetism-tuning strategies for graphene oxide based on magnetic oligoacene oxide
      patches model.
AB  - Graphene oxide (GO) has wide application potential owing to its 2D structure and
      diverse modification sites for various targeted uses. The introduction of
      magnetism into GO structures has further advanced the controllability of the
      application of GO materials. Herein, the concept of modular design and modeling
      was applied to tune the magnetism of GO. To obtain desirable magnetic properties,
      diradical-structured GO patches were formed by the introduction of two functional
      groups to break the Kekule structure of the benzene ring. In these diradical GO
      patches, the energy of the triplet state was lower than those of the open-shell
      broken-symmetry singlet state and closed-shell singlet state. To create such
      multi-radical patches, a practical approach is to determine a substantial spatial
      separation of the alpha and beta spin densities in the molecule. Thus, systematic
      design strategies and tests were evaluated. The first strategy was extending the
      distance between the distribution center of the alpha and beta spin densities;
      the second was controlling the delocalization directions of the alpha and beta
      electrons; the third was controlling the delocalization extension of the alpha
      and beta electrons by oxidative modification, and finally introducing multi
      radical structures into the molecular system and controlling the position of each
      radical. Herein, successful molecular models with a large magnetic coupling
      constant (~3600 cm-1) were obtained. This study paves the way to explore
      ferromagnetic MGO guided by theoretical study, which may become reality soon.

PMID- 29344590
TI  - Magnetic anisotropy investigation on light lanthanide complexes.
AB  - Herein, a series of light lanthanide-based complexes, Ln(fdh)3(bpy) (Ln = CeIII,
      PrIII, and NdIII and fdh = 1,1,1-fluoro-5,5-dimethyl-hexa-2,4-dione, bpy = 2,2'
      bipyridine), were synthesized and characterized. The angle-resolved magnetometry
      studies reveal that the three complexes have Ising-type anisotropy, and the
      magnetic easy axes orient along the negative charge dense direction in the
      crystal field. The results were consistent with the ab initio calculations. This
      research demonstrates that the crystal field electron density distribution
      determines the anisotropy of light lanthanides.

PMID- 29344591
TI  - Introduction of axial chirality at a spiro carbon atom in the synthesis of
      pentaerythritol-imine macrocycles.
AB  - Novel chiral macrocyclic polyimines with spiro carbon atoms are described. The
      key feature of the synthesis is the formation of an axially chiral quaternary
      carbon atom having four constitutionally identical substituents. This is possible
      either by the freezing of the labile conformation of a spiro-diboronate moiety or
      by the diastereomeric fitting of a conformationally stable spiro-acetal moiety
      into a chiral framework. A general model for the description of this type of
      axial chirality is proposed.

PMID- 29344592
TI  - pH-Responsible fluorescent carbon nanoparticles for tumor selective theranostics
      via pH-turn on/off fluorescence and photothermal effect in vivo and in vitro.
AB  - We developed nanoparticles comprising a photothermal dye (IR825)-loaded
      carbonized zwitterionic polymer [FNP-I] as "switch-on" pH-responsive fluorescence
      probes to sense intracellular cancer cells and for near-infrared (NIR)
      controllable photothermal therapy (PTT) in vivo and in vitro. The fluorescent
      "off" of FNP-I was activated after reaching the cancer cell environment, where
      the zwitterionic compartment of FNP lost its hydrophobicity to induce PTT
      mediated heat release of IR825 under NIR irradiation in the tumor. Approximately
      100% of the IR825 was released from the FNP core to generate high thermal
      conversion to completely kill the cancer cells. Furthermore, after intravenous
      treatment of FNP-I into MDAMB-231-cell bearing mice, pH-responsive photothermal
      therapy was observed, achieving marked ablation of tumor cells with release of
      IR825 under tumor environment conditions. In addition, fluorescent signals were
      clearly found at the tumor site after 3 h, decreasing at the 6 h time point. The
      in vitro and in vivo detection system demonstrated good cellular uptake and
      biocompatibility as a potential imaging-guided photothermal therapy nanotool for
      cancer treatment. Interestingly, the synergism of the biosensor and PTT in single
      FNP-I platform led to more effective cancer cell killing than either monotherapy,
      providing a new approach for cancer treatment.

PMID- 29344593
TI  - Biologically inspired oxidation catalysis using metallopeptides.
AB  - The stereoselective oxidation of hydrocarbons is one of the most challenging
      reactions for synthetic chemists. However, this transformation is one of the most
      common reactions in nature. Metalloenzymes that catalyze this transformation are
      taken as inspiration for the development of new catalysts. There are several
      examples in the literature where either peptides or metal catalysts are used in
      the stereoselective oxidation reaction, but the synergistic combination of both
      systems is still a non-explored field. The use of metallopeptides in biologically
      inspired oxidation reactions is discussed in this perspective.

PMID- 29344594
TI  - Lithiation of palladated dihydropentacene: a new route for the introduction of
      substituents from both of electrophiles and nucleophiles to pentacene.
AB  - Dibromodihydropentacene compound 1 was palladated and then lithiated to give a
      lithiated-palladated intermediate. Both of the lithium moiety and the palladium
      complex moiety on dihydropentacene unexpectedly survived in the solution. The Li
      and Pd moieties reacted with electrophiles and nucleophiles respectively to give
      the substituted dihydropentacene products. Aromatization of these
      dihydropentacenes gave substituted pentacene derivatives.

PMID- 29344595
TI  - Quantitative characterization of the ionic mobility and concentration in Li
      battery cathodes via low frequency electrochemical strain microscopy.
AB  - Electrochemical strain microscopy (ESM) can provide useful information on the
      ionic processes in materials at the local scale. This is especially important for
      ever growing applications of Li-batteries whose performance is limited by the
      intrinsic and extrinsic degradation. However, the ESM method used so far has been
      only qualitative due to multiple contributions to the apparent ESM signal. In
      this work, we provide a viable approach for the local probing of ionic
      concentration and diffusion coefficients based on the frequency dependence of the
      ESM signal. A theoretical basis considering the dynamic behavior of ion migration
      and relaxation and change of ion concentration profiles under the action of the
      electric field of the ESM tip is developed. We argue that several parasitic
      contributions to the ESM signal discussed in the literature can be thus
      eliminated. The analysis of ESM images using the proposed approach allows a
      quantitative mapping of the ionic diffusion coefficients and concentration in
      ionic conductors. The results are validated on Li-battery cathodes (LiMn2O4)
      extracted from commercial Li-batteries and can provide novel possibilities for
      their development and further insight into the mechanisms of their degradation.

PMID- 29344596
TI  - Superstructure Ta2O5 mesocrystals derived from (NH4)2Ta2O3F6 mesocrystals with
      efficient photocatalytic activity.
AB  - Superstructured mesocrystalline Ta2O5 nanosheets were successfully prepared from
      mesocrystalline (NH4)2Ta2O3F6 nanorods by the annealing method for the first
      time. The as-prepared mesocrystalline Ta2O5 nanosheets in this work showed
      remarkable visible light absorption, mainly due to the formation of oxygen
      vacancy defects in the mesocrystalline Ta2O5 nanosheets, which was also confirmed
      by XPS spectra, Raman spectra and EPR spectra. Besides, the mesocrystalline Ta2O5
      nanosheets showed a highly enhanced photocatalytic activity of 11 268.24 MUmol g
      1 h-1, about 3.95 times that of commercial Ta2O5. Moreover, the specific surface
      area of the mesocrystalline Ta2O5-800 nanosheets was 16.34 m2 g-1, about 5.32
      times that of the commercial Ta2O5 (3.072 m2 g-1). The valence band XPS spectra
      indicated a strong oxidizing ability of the mesocrystalline Ta2O5 nanosheets in
      comparison to that of commercial Ta2O5. The formation of superstructured Ta2O5
      mesocrystals generated long lifetime carriers and effective conduction pathways,
      which greatly enhanced the photocatalytic activity for hydrogen production.

PMID- 29344597
TI  - Rapid localized crystallization of lysozyme by laser trapping.
AB  - Confining protein crystallization to a millimetre size was achieved within 0.5 h
      after stopping 1 h intense trapping laser irradiation, which shows excellent
      performance in spatial and temporal controllability compared to spontaneous
      nucleation. A continuous-wave near-infrared laser beam is tightly focused into a
      glass/solution interfacial layer of a supersaturated buffer solution of hen egg
      white lysozyme (HEWL). The crystallization is not observed during laser trapping,
      but initiated by stopping the laser irradiation. The generated crystals are
      localized densely in a circular area with a diameter of a few millimetres around
      the focal spot and show specific directions of the optical axes of the HEWL
      crystals. To interpret this unique crystallization, we propose a mechanism that
      nucleation and the subsequent growth take place in a highly concentrated domain
      consisting of HEWL liquid-like clusters after turning off laser trapping.

PMID- 29344598
TI  - Hot kinetic model as a guide to improve organic photovoltaic materials.
AB  - The modeling of organic solar cells (OSCs) can provide a roadmap for their
      further improvement. Many OSC models have been proposed in recent years; however,
      the impact of the key intermediates from photons to electricity-hot charge
      transfer (CT) states-on the OSC efficiency is highly ambiguous. In this study, we
      suggest an analytical kinetic model for OSC that considers a two-step charge
      generation via hot CT states. This hot kinetic model allowed us to evaluate the
      impact of different material parameters on the OSC performance: the driving force
      for charge separation, optical bandgap, charge mobility, geminate recombination
      rate, thermalization rate, average electron-hole separation distance in the CT
      state, dielectric permittivity, reorganization energy and charge delocalization.
      In contrast to a widespread trend of lowering the material bandgap, the model
      predicts that this approach is only efficient along with improvement of the other
      material properties. The most promising ways to increase the OSC performance are
      decreasing the reorganization energy, i.e., an energy change accompanying CT from
      the donor molecule to the acceptor, increasing the dielectric permittivity and
      charge delocalization. The model suggests that there are no fundamental
      limitations that can prevent achieving the OSC efficiency above 20%.

PMID- 29344599
TI  - Water thermophoresis in carbon nanotubes: the interplay between thermophoretic
      and friction forces.
AB  - Thermophoresis is the phenomenon wherein particles experience a net drift induced
      by a thermal gradient. In this work, molecular dynamics simulations are conducted
      to study with atomistic detail the thermophoresis of water nanodroplets inside
      carbon nanotubes (CNTs) and its interplay with the retarding liquid-solid
      friction. Different applied temperatures, thermal gradients, and droplet sizes
      are used to reveal the dynamics of the two kinetic regimes of the thermophoretic
      motion in CNTs. The results indicate that during the droplet motion, the
      thermophoretic force is independent of the velocity of the droplet, whereas the
      magnitude of the retarding friction force exhibits a linear dependence. In fact,
      in the initial regime the magnitude of the friction force increases linearly with
      the droplet velocity, until the thermophoretic force is balanced by the friction
      force as the droplet reaches its terminal velocity in the final regime. In
      addition, an increase in the magnitude of the thermophoretic force is found for
      longer water droplets. These findings provide a deeper understanding of liquid
      transport driven by temperature gradients in nanoconfined geometries where liquid
      solid interfaces govern fluidics.

PMID- 29344604
TI  - Advancing Clinical Improvements for Patients Using the Theory-Driven and Data
      Driven Branches of Computational Psychiatry.

PMID- 29344605
TI  - Errors in Tables, Author Affiliation, and Online-Only Supplement.

PMID- 29344606
TI  - Errors in Figure and Table 3.

PMID- 29344607
TI  - Bosentan for Cutaneous Ulcers in Anti-MDA5 Dermatomyositis.

PMID- 29344608
TI  - Nonhealing Crusted Scalp Lesions in a 4-Year-Old Boy.

PMID- 29344609
TI  - Generalized Lichen Nitidus Following Anti-PD-1 Antibody Treatment.

PMID- 29344611
TI  - Variable Response to Naltrexone in Patients With Hailey-Hailey Disease.

PMID- 29344610
TI  - Association of Combined Patterns of Tobacco and Cannabis Use in Adolescence With
      Psychotic Experiences.
AB  - Importance: There is concern about potentially causal effects of tobacco use on
      psychosis, but epidemiological studies have been less robust in attempts to
      minimize effects of confounding than studies of cannabis use have been.
      Objectives: To examine the association of patterns of cigarette and cannabis use
      with preceding and subsequent psychotic experiences, and to compare effects of
      confounding across these patterns. Design, Setting, and Participants: This cohort
      study used data from the Avon Longitudinal Study of Parents and Children, which
      initially consisted of 14 062 children. Data were collected periodically from
      September 6, 1990, with collection ongoing, and analyzed from August 8, 2016,
      through June 14, 2017. Cigarette and cannabis use data were summarized using
      longitudinal latent class analysis to identify longitudinal classes of substance
      use. Associations between classes and psychotic experiences at age 18 years were
      assessed. Exposures: Depending on the analysis model, exposures were longitudinal
      classes of substance use or psychotic experiences at age 12 years. Main Outcomes
      and Measures: Logistic regression was used to examine the associations between
      substance use longitudinal classes and subsequent onset of psychotic experiences.
      Results: Longitudinal classes were derived using 5300 participants (56.1% female)
      who had at least 3 measures of cigarette and cannabis use from ages 14 to 19
      years. Prior to adjusting for a range of potential confounders, there was strong
      evdience that early-onset cigarette-only use (4.3%), early-onset cannabis use
      (3.2%), and late-onset cannabis use (11.9%) (but not later-onset cigarette-only
      use [14.8%]) latent classes were associated with increased psychotic experiences
      compared with nonusers (65.9%) (omnibus P < .001). After adjusting for
      confounders, the association for early-onset cigarette-only use attenuated
      substantially (unadjusted odds ratio [OR], 3.03; 95% CI, 1.13-8.14; adjusted OR,
      1.78; 95% CI, 0.54-5.88), whereas those for early-onset cannabis use (adjusted
      OR, 3.70; 95% CI, 1.66-8.25) and late-onset cannabis use (adjusted OR, 2.97; 95%
      CI, 1.63-5.40) remained consistent. Conclusions and Relevance: In this study, our
      findings indicate that while individuals who use cannabis or cigarettes during
      adolescence have an increased risk of subsequent psychotic experiences,
      epidemiological evidence is substantively more robust for cannabis use than it is
      for tobacco use.

PMID- 29344613
TI  - Role of Preoperative Variables in Reducing the Rate of Occult Invasive Disease
      for Women Considering Active Surveillance for Ductal Carcinoma In Situ-Reply.

PMID- 29344612
TI  - Association of Disease Severity With Skin Microbiome and Filaggrin Gene Mutations
      in Adult Atopic Dermatitis.
AB  - Importance: Skin microbiome correlates with disease severity for lesional and
      nonlesional skin, indicating a global influence of atopic dermatitis (AD). A
      relation between skin microbiome and filaggrin gene (FLG) mutations proposes a
      possible association between skin microbiome and host genetics. Objectives: To
      assess skin and nasal microbiome diversity and composition in patients with AD
      and compare with healthy controls, and to investigate the microbiome in relation
      to disease severity and FLG mutations in patients with AD. Design, Setting, and
      Participants: An observational case-control study of 45 adult healthy controls
      and 56 adult patients with AD was carried out from January 2015 to June 2015 in a
      tertiary referral center, Department of Dermatology, Bispebjerg Hospital,
      Denmark. Exposures: Bacterial swabs were taken from patients with AD (lesional
      skin, nonlesional skin, and anterior nares) and from healthy controls
      (nonlesional skin and anterior nares). Eczema severity was assessed and FLG
      mutations noted. Bacterial DNA was extracted from swabs, and V3-V4 16S rDNA
      regions amplified with PCR. Samples were analyzed at Statens Serum Institut
      September 2015 to September 2016. Bioinformatics analyses of the microbiome were
      analyzed using R statistical software (version 3.3.1, R Foundation Inc). Main
      Outcomes and Measures: Skin microbiomes were investigated using next-generation
      sequencing targeting 16S ribosomal RNA. Results: Microbiome alpha diversity was
      lower in patients with AD compared with healthy controls in nonlesional skin
      (effect size, 0.710; 95% CI, 0.27-1.15; P = .002), lesional skin (effect size,
      0.728; 95% CI, 0.35-1.33; P = .001), and nose (effect size, 1.111; 95% CI, 0.48
      0.94; P < .001). Alpha diversity was inversely correlated with disease severity
      for lesional (effect size, 0.530; 95% CI, 0.23-1.64; P = .02) and nonlesional
      skin (effect size, 0.451; 95% CI, 0.04-2.44; P = .04) in patients with AD.
      Microbiome composition in AD nonlesional skin was linked to FLG mutations.
      Conclusions and Relevance: An altered microbiome composition in patients with AD
      in nonlesional skin, lesional skin, as well as nose, suggests a global influence
      of AD. Microbiome composition in AD nonlesional skin is associated with FLG
      mutations, proposing a possible association between the skin microbiome and host
      genetics.

PMID- 29344614
TI  - Apprehending Otherness Through Wonder: A Facial Plastic Surgeon's Review of the
      Book and Movie.

PMID- 29344615
TI  - A 30-Year-Old Man With Recurrent Dyspnea and Palpitations.

PMID- 29344616
TI  - Ensuring Timely Access to Quality Care for US Veterans.

PMID- 29344617
TI  - Eliminating Alcohol-Impaired Driving Fatalities: What Can Be Done?

PMID- 29344618
TI  - The Heart-Brain Team-Towards Optimal Team-Based Coordinated Care.

PMID- 29344619
TI  - Acoustic Analysis of Voice in Singers: A Systematic Review.
AB  - Purpose: Singers are vocal athletes having specific demands from their voice and
      require special consideration during voice evaluation. Presently, there is a lack
      of standards for acoustic evaluation in them. The aim of the present study was to
      systematically review the available literature on the acoustic analysis of voice
      in singers. Method: A systematic review of studies on acoustic analysis of voice
      in singers (PubMed/MEDLINE, CINAHL, Scopus, ProQuest, Cochrane, Ovid, Science
      Direct, and Shodhganga) was carried out. Key words based on PIO (population
      investigation-outcome) were used to develop search strings. Titles and abstracts
      were screened independently, and appropriate studies were read in full for data
      extraction. Results: Of the 895 studies, 26 studies met the inclusion criteria.
      Great variability was noted in the instruments and task used. Different acoustic
      measures were employed, such as fundamental frequency, perturbation, cepstral,
      spectral, dysphonia severity index, singing power ratio, and so forth.
      Conclusion: Overall, a great heterogeneity was noted regarding population, tasks,
      instruments, and parameters. There is a lack of standardized criteria for the
      evaluation of singing voice. In order to implement acoustic analysis as a part of
      comprehensive voice evaluation exclusively for singers, there is a certain need
      for methodical sound studies.

PMID- 29344621
TI  - Role of Preoperative Variables in Reducing the Rate of Occult Invasive Disease
      for Women Considering Active Surveillance for Ductal Carcinoma In Situ.

PMID- 29344620
TI  - Association of Depression With Mortality in Older Adults Undergoing Transcatheter
      or Surgical Aortic Valve Replacement.
AB  - Importance: Depression is increasingly recognized as a risk factor for adverse
      outcomes in cardiovascular disease. However, little is known about depression in
      older adults undergoing transcatheter (TAVR) or surgical (SAVR) aortic valve
      replacement. Objective: To determine the prevalence of depression and its
      association with all-cause mortality in older adults undergoing TAVR or SAVR.
      Design, Setting, and Participants: This preplanned analysis of the Frailty Aortic
      Valve Replacement (FRAILTY-AVR) prospective cohort study included 14 centers in 3
      countries from November 15, 2011, through April 7, 2016. Individuals 70 years or
      older who underwent TAVR or SAVR were enrolled. Depressive symptoms were
      evaluated using the Geriatric Depression Scale Short Form at baseline and follow
      up. Main Outcomes and Measures: All-cause mortality at 1 and 12 months after TAVR
      or SAVR. Logistic regression was used to determine the association of depression
      with mortality after adjusting for confounders such as frailty and cognitive
      impairment. Results: Among 1035 older adults (427 men [41.3%] and 608 women
      [58.7%]) with a mean (SD) age of 81.4 (6.1) years, 326 (31.5%) had a positive
      result of screening for depression, whereas only 89 (8.6%) had depression
      documented in their clinical record. After adjusting for clinical and geriatric
      confounders, baseline depression was found to be associated with mortality at 1
      month (odds ratio [OR], 2.20; 95% CI, 1.18-4.10) and at 12 months (OR, 1.532; 95%
      CI, 1.03-2.24). Persistent depression, defined as baseline depression that was
      still present 6 months after the procedure, was associated with a 3-fold increase
      in mortality at 12 months (OR, 2.98; 95% CI, 1.08-8.20). Conclusions and
      Relevance: One in 3 older adults undergoing TAVR or SAVR had depressive symptoms
      at baseline and a higher risk of short-term and midterm mortality. Patients with
      persistent depressive symptoms at follow-up had the highest risk of mortality.

PMID- 29344622
TI  - Barriers to and Facilitators of Implementing Enhanced Recovery Pathways Using an
      Implementation Framework: A Systematic Review.

PMID- 29344625
TI  - Perception of Cantonese Lexical Tones by Pediatric Cochlear Implant Users.
AB  - Purpose: The purpose of this study is to assess Cantonese word recognition and
      the discrimination of Cantonese tones with manipulated contours by child and
      adolescent cochlear implant (CI) users and a group of peers with normal hearing
      (NH). It was hypothesized that the CI users would perform more poorly than their
      counterparts with NH in both tasks and that CI users implanted before 2 years of
      age would perform better than those implanted after 2 years. Method: Forty-one
      participants were recruited from hospitals, schools, and kindergartens in Hong
      Kong: Ten CI users implanted at or before 2 years of age ("early" CI group), 13
      CI users implanted after 2 years of age ("late" CI group), and 18 individuals
      with NH. The mean age at implantation of the early CI group was 1.5 years (SD =
      0.3), and for the late CI group, it was 4.3 years (SD = 2.1). Participants were a
      mean of 13.3 years of age (SD = 3.7) at time of testing. Participants completed a
      Cantonese word recognition test and a discrimination task using Cantonese tones
      with modified fundamental frequency trajectories. Results: Both CI user groups
      obtained significantly lower scores than the group with NH on the word
      recognition test. Mean percent correct scores for the word recognition test were
      79% for the early CI group, 69% for the late CI group, and 97% for the group with
      NH. The group with NH consistently achieved higher scores than the CI user groups
      when discriminating manipulated Cantonese tones. Increasing the acoustic
      difference between tones improved discrimination performance for CI users for
      level tone contrasts only. CI users implanted at or before 2 years of age
      obtained higher scores than those implanted later. Conclusions: The results of
      this study add further evidence that children using CIs do not perform as well as
      peers in perceiving Cantonese tones. Modification of tones to increase pitch
      range did not consistently improve the ability of children with implants to
      perceive the difference between tones. Further research is required to fully
      assess potential benefits of early implantation for speakers of tonal languages.
      Supplemental Materials: https://doi.org/10.23641/asha.5782209.

PMID- 29344627
TI  - Error in Author Affiliations.

PMID- 29344626
TI  - Is Depression an Important New Mortality Risk Factor After Aortic Valve
      Replacement or Simply a Component of the Geriatric Disease Spectrum?

PMID- 29344628
TI  - Errors in Abstract, Text, and Figure 1 and Addition of Open Access.

PMID- 29344631
TI  - A Brief Exposure-Based Treatment vs Cognitive Processing Therapy for
      Posttraumatic Stress Disorder: A Randomized Noninferiority Clinical Trial.
AB  - Importance: Written exposure therapy (WET), a 5-session intervention, has been
      shown to efficaciously treat posttraumatic stress disorder (PTSD). However, this
      treatment has not yet been directly compared with a first-line PTSD treatment
      such as cognitive processing therapy (CPT). Objective: To determine if WET is
      noninferior to CPT in patients with PTSD. Design, Setting, and Participants: In
      this randomized clinical trial conducted at a Veterans Affairs medical facility
      between February 28, 2013, and November 6, 2016, 126 veteran and nonveteran
      adults were randomized to either WET or CPT. Inclusion criteria were a primary
      diagnosis of PTSD and stable medication therapy. Exclusion criteria included
      current psychotherapy for PTSD, high risk of suicide, diagnosis of psychosis, and
      unstable bipolar illness. Analysis was performed on an intent-to-treat basis.
      Interventions: Participants assigned to CPT (n = 63) received 12 sessions and
      participants assigned to WET (n = 63) received 5 sessions. The CPT protocol that
      includes written accounts was delivered individually in 60-minute weekly
      sessions. The first WET session requires 60 minutes while the remaining 4
      sessions require 40 minutes. Main Outcomes and Measures: The primary outcome was
      the total score on the Clinician-Administered PTSD Scale for DSM-5;
      noninferiority was defined by a score of 10 points. Blinded evaluations were
      conducted at baseline and 6, 12, 24, and 36 weeks after the first treatment
      session. Treatment dropout was also examined. Results: For the 126 participants
      (66 men and 60 women; mean [SD] age, 43.9 [14.6] years), improvements in PTSD
      symptoms in the WET condition were noninferior to improvements in the CPT
      condition at each of the assessment periods. The largest difference between
      treatments was observed at the 24-week assessment (mean difference, 4.31 points;
      95% CI, -1.37 to 9.99). There were significantly fewer dropouts in the WET vs CPT
      condition (4 [6.4%] vs 25 [39.7%]; chi21 = 12.84, Cramer V = 0.40). Conclusions
      and Relevance: Although WET involves fewer sessions, it was noninferior to CPT in
      reducing symptoms of PTSD. The findings suggest that WET is an efficacious and
      efficient PTSD treatment that may reduce attrition and transcend previously
      observed barriers to PTSD treatment for both patients and providers. Trial
      Registration: clinicaltrials.gov Identifier: NCT01800773.

PMID- 29344632
TI  - Factors Associated With Outcomes and Costs After Pediatric Laparoscopic
      Cholecystectomy.
AB  - Importance: The prevalence of pediatric cholelithiasis is increasing with the
      epidemic of childhood obesity. With this rise, the outcomes and costs of
      pediatric laparoscopic cholecystectomy become an important public health and
      economic concern. Objective: To assess patient and health system factors
      associated with the outcomes and costs after laparoscopic cholecystectomy among
      Canadian children. Design, Setting, and Participants: This was a retrospective,
      population-based study of children 17 years and younger undergoing laparoscopic
      cholecystectomy from April 1, 2008, until March 31, 2015. The data source was the
      Canadian Institute for Health Information. The Canadian Institute for Health
      Information Discharge Abstract Database includes data from all Canadian
      hospitals. The analysis was limited to inpatient cholecystectomies. All Canadian
      children undergoing laparoscopic cholecystectomy were included. Exposure: The
      exposure in this study was laparoscopic cholecystectomy. Main Outcomes and
      Measures: The primary outcome was all-cause morbidity, a composite outcome of any
      complication that prolonged length of stay by 24 hours or required a second,
      unplanned procedure. The cost of the index admission was also calculated as a
      secondary outcome. These outcomes of interest were determined before data
      analysis. Odds ratios and 95% CIs were estimated using multilevel logistic
      regression models. Results: During the study period, 3519 laparoscopic
      cholecystectomies were performed; of these, 79.1% (n = 2785) were in girls, and
      98.0% (n = 3450) were for gallstone disease. The overall morbidity rate was 3.9%
      (n = 137). After adjustment, patients with comorbidities were more susceptible to
      morbidity (odds ratio, 2.68; 95% CI, 1.78-3.86; P < .001). Operations for
      gallstones were less morbid. High-volume general surgeons had lower morbidity
      rates compared with low-volume pediatric surgeons (odds ratio, 0.32; 95% CI, 0.12
      0.69; P = .005) independent of pediatric volumes. The mean (SD) unadjusted cost
      of a laparoscopic cholecystectomy was $4115 ($7273). Operative indication,
      complications, comorbidities, emergency admission, and surgeon volume were
      associated with cost. Conclusions and Relevance: The high-volume nature of adult
      general surgery translated to lower morbidity and cost after pediatric
      laparoscopic cholecystectomy, suggesting that adult volume is associated with
      pediatric outcomes. As the rate of pediatric gallstone disease increases, surgeon
      volume, rather than specialty training, should be considered when pursuing
      operative management.

PMID- 29344633
TI  - Considering the Ability of General Surgeons to Add Value to Pediatric Surgery.

PMID- 29344634
TI  - Underlying mechanism of the photodynamic activity of hematoporphyrin-induced
      apoptosis in U87 glioma cells.
AB  - Photodynamic therapy (PDT) is a relatively novel type of tumor therapy method
      with low toxicity and limited side-effects. The aim of the present study was to
      investigate the underlying mechanism and potential microRNAs (miRNAs) involved in
      the treatment of glioma by PDT with hematoporphyrin, a clinical photosensitizer.
      The photodynamic activity of hematoporphyrin on the cell viability and apoptosis
      of gliomas was investigated by MTT, and flow cytometry and fluorescence
      microscopy, respectively. Alterations in singlet oxygen and mitochondrial
      membrane potential were detected. The differentially expressed miRNAs and
      proteins were evaluated by miRNA gene chip and apoptosis-associated protein chip,
      respectively. The results demonstrated that cell viability significantly
      decreased with hematoporphyrin concentration. PDT with hematoporphyrin
      significantly increased cell apoptosis at a later stage, induced the content of
      reactive oxygen species (ROS) and decreased the mitochondrial membrane potential,
      indicating that PDT with hematoporphyrin inhibited cell growth via induction of
      radical oxygen, decreased the mitochondrial membrane potential and induced
      apoptosis. The upregulated miRNAs, including hsa-miR-7641, hsa-miR-9500, hsa-miR
      4459, hsa-miR-21-5p, hsa-miR-663a and hsa-miR-205-5p may be important in PDT
      induced cell apoptosis in glioma. Transporter 1, ATP binding cassette subfamily B
      member- and nuclear factor-kappaB-mediated apoptosis signaling pathways were the
      most significant pathways. Thus, the current study presents PDT as a potential
      therapeutic approach for the treatment of malignant glioma, and identified miRNAs
      for the molecular design and development of a third-generation photosensitizer
      (PS).

PMID- 29344635
TI  - Eradication of cervical cancer in vivo by an AAV vector that encodes shRNA
      targeting human papillomavirus type 16 E6/E7.
AB  - The major causative agent of cervical cancer is human papilloma virus (HPV); the
      viral proteins E6 and E7 induce carcinogenesis through the inactivation of the
      host tumor-suppressor gene. Therefore, the stable expression of specific
      inhibitors of E6 and E7 in cancer cells is expected to provide effective
      treatment for cervical cancer without affecting normal tissue. In this study, we
      propose a novel therapeutic approach using an adeno-associated virus (AAV) vector
      encoding short hairpin RNA (shRNA) against the oncoproteins E6 and E7 (shE6E7) of
      HPV type 16 (HPV-16), termed AAV-shE6E7. Three different HPV-16-positive cervical
      cancer cell lines (BOKU, SiHa and SKG-IIIa cells) were tested for gene transfer
      efficiency using serotypes of AAV vectors. For in vitro analysis, the cells were
      transduced AAV-shE6E7; alternatively, in vivo studies were performed via the
      administration of a direct injection of AAV-shE6E7 into cervical cancer cell
      derived tumors in mice. The high gene transfer efficiency was observed using AAV2
      in all three cervical cancer cell lines. Following transduction, we observed
      apoptosis, G1 phase arrest and cell growth inhibition. Additionally, in the
      transduced cells, the E6, E7 and p16 expression levels decreased, whereas the
      expression levels of p53, p21 and pRb levels were enhanced. The growth of
      subcutaneously transplanted tumors was markedly inhibited by the single
      administration of AAV2-shE6E7, and the tumors were almost completely eradicated
      without any adverse effects. These results provided evidence of the utility of
      AAV2-shE6E7 as a novel treatment approach for cervical cancer.

PMID- 29344636
TI  - Analysis of the prolonged infusion of DFP-10917, a deoxycytidine analog, as a
      therapeutic strategy for the treatment of human tumor xenografts in vivo.
AB  - 2'-C-cyano-2'-deoxy-1-beta-D-arabino-pentofranocyl-cytosine (DFP-10917, CNDAC) is
      a 2'-deoxycytidine analog with antitumor activity against various tumor cells.
      However, a clinically available therapeutic regimen for this compound needs to be
      established and its functional mechanisms in relation to the dosing schedule need
      to be clarified. In this study, we evaluated the antitumor activity and toxicity
      of DFP-10917 by varying the dose and administration schedule in human solid tumor
      and leukemia xenografts in vivo. Compared to a 1-day infusion with a high-dose of
      DFP-10917 (30 mg/kg/day), a prolonged 14-day infusion with a low-dose (4.5
      mg/kg/day) exerted superior tumor growth inhibitory effects without decreasing
      the body weights of mice in our human tumor xenograft model. In addition, we
      found that a 14-day infusion of low-dose DFP-10917 markedly prolonged the
      lifespan of nude mice bearing both acute leukemia and ovarian cancer cell-derived
      tumors. On the other hand, gemcitabine (GEM) and cytosine arabinoside (Ara-C),
      which are similar deoxycytidine analogs and are widely used clinically as
      standard regimens, exerted less potent antitumor effects than DFP-10917 on these
      tumors. To elucidate the possible functional mechanisms of the prolonged infusion
      of DFP-10197 compared with that of GEM or Ara-C, the rate of DNA damage in CCRF
      CEM and HeLa cells treated with DFP-10917, Ara-C and GEM was detected using a
      comet assay. DFP-10917, at a range of 0.05 to 1 uM, induced a clear tailed-DNA
      pattern in both the CCRF-CEM and HeLa cells; Ara-C and GEM did not have any
      effect. It was thus suggested that a low concentration and long-term exposure to
      DFP-10917 aggressively introduced the fragmentation of DNA molecules, namely the
      so-called double-strand breaks in tumor cells, leading to potent cytotoxicity.
      Moreover, treatment with DFP-10917 at a low-dose with a long-term exposure
      specifically increased the population of cells in the G2/M phase, while GEM
      reduced this cell population, suggesting a unique function (G2/M arrest) of DFP
      10917. On the whole, our findings indicate that the prolonged infusion of low
      dose DFP-10917 mainly displays a novel functional mechanism as a DNA-damaging
      drug and may thus prove to be useful in the treatment of cancer patients who are
      resistant to other cytosine nucleosides, or in patients in which these other
      nucleosides have been shown to be ineffective.

PMID- 29344637
TI  - miR-186, a serum microRNA, induces endothelial cell apoptosis by targeting SMAD6
      in Kawasaki disease.
AB  - Kawasaki disease (KD) is an acute, self-limited vasculitis that predominantly
      affects medium-sized arteries, particularly the coronary arteries. Recent studies
      have indicated that microRNAs are involved in many diseases, including KD.
      However, the detailed mechanism remains unclear. The aim of the present study was
      to explore the role of miR-186 in KD and potentially discover a new target for KD
      treatment. The results demonstrated that miR-186 was upregulated in serum from
      patients with KD and KD serum could increase miR-186 transcript levels in
      endothelial cells (HUVECs). Overexpression of miR-186 mimic induced HUVEC
      apoptosis through mitogen-activated protein kinase (MAPK) activation by targeting
      and inhibiting SMAD family member 6 (SMAD6). Furthermore, KD serum induced HUVEC
      apoptosis through miR-186. In conclusion, the present results suggested that KD
      serum-associated miR-186 has an essential role in endothelial cell apoptosis by
      activating the MAPK pathway through targeting the SMAD6 gene.

PMID- 29344638
TI  - Garcinone C exerts antitumor activity by modulating the expression of
      ATR/Stat3/4E-BP1 in nasopharyngeal carcinoma cells.
AB  - Nasopharyngeal carcinoma (NPC) is one of the most common head and neck
      malignancies and is typically treated with radiotherapy and chemotherapy.
      Garcinone C, a natural compound isolated from Garcinia oblongifolia Champ., is a
      xanthone derivative with potential cytotoxic effects on certain cancers. However,
      there are limited studies regarding its effects on NPC cells, and its mechanism
      of action in NPC remains unknown. In the present study, we found that garcinone C
      significantly inhibited cell viability of the human NPC cell lines CNE1, CNE2,
      HK1 and HONE1. This inhibition was exerted in a time- and dose-dependent manner.
      Flow cytometry demonstrated that garcinone C arrested the cell cycle at the S
      phase. Moreover, with 10 uM of high-dose garcinone C treatment, the cells
      exhibited necrotic morphology changes including cell swelling, rough endoplasmic
      reticulum degranulation, endoplasmic reticulum dilatation, mitochondrial swelling
      and vacuolar degeneration. In addition, we found that garcinone C stimulated the
      expression levels of ATR and 4E-BP1, while efficiently inhibiting the expression
      levels of cyclin B1, cyclin D1, cyclin E2, cdc2, CDK7 and Stat3. Collectively,
      the ability of garcinone C to inhibit NPC in growth in vitro suggested that
      garcinone C may be a novel agent for the management of NPC.

PMID- 29344639
TI  - Therapeutic potential of a dual mTORC1/2 inhibitor for the prevention of
      posterior capsule opacification: An in vitro study.
AB  - Mammalian target of rapamycin (mTOR) serves a central role in regulating cell
      growth and survival, and has been demonstrated to be involved in the pathological
      progression of posterior capsule opacification (PCO). In the present study, the
      potency of PP242, a novel dual inhibitor of mTOR complex 1/2 (mTORC1/2), in the
      suppression of the growth of human lens epithelial cells (HLECs) was
      investigated. Using a Cell Counting Kit-8 and a wound healing assay, it was
      demonstrated that PP242 inhibited the proliferation and migration of HLECs. In
      addition, western blot analysis indicated that PP242 completely inhibited mTORC1
      and mTORC2 downstream signaling activities, whereas rapamycin only partially
      inhibited mTORC1 activity within LECs. Furthermore, PP242 treatment led to an
      upregulation of the expression levels of p53 and B cell lymphoma-2 (Bcl-2)
      associated X and downregulation of Bcl-2. In addition, flow cytometric analysis
      demonstrated that PP242 induced the cell cycle arrest at the G0/G1 phase, which
      may have caused apoptosis and induced autophagy within the LECs. The results of
      the present study suggested that administration of PP242 may potentially offer a
      novel therapeutic approach for the prevention of PCO.

PMID- 29344640
TI  - Over-regulation of microRNA-133b inhibits cell proliferation of cisplatin-induced
      non-small cell lung cancer cells through PI3K/Akt and JAK2/STAT3 signaling
      pathway by targeting EGFR.
AB  - The present study determined the anticancer activity and its mechanism of
      microRNA-133b on cell proliferation of cisplatin-induced non-small cell lung
      cancer cells. The expression of microRNA-133b cisplatin-induced non-small cell
      lung cancer (NSCLC) tissue was lower than that of para-carcinoma tissue in
      patients. Overall survival of higher expression in cisplatin-induced NSCLC
      patients was higher than that of lower expression in cisplatin-induced NSCLC
      patients. Over-regulation of microRNA-133b inhibited cell proliferation and LDH
      activity, induced apoptosis and caspase-3 activity, suppressed the protein
      expression of EGFR, PI3K, p-Akt, p-JAK2 and p-STAT3, decreased cyclin D1 and
      increased Bax protein expression in cisplatin-induced A549 cells. EGFR inhibitor
      (lapatinib) suppressed EGFR protein expression, inhibited cell proliferation and
      LDH activity, and induced apoptosis and caspase-3 activity in cisplatin-induced
      A549 cells by over-regulation of microRNA-133b. When EGFR protein expression was
      suppressed, PI3K, p-Akt, p-JAK2 and p-STAT3, decreased cyclin D1 and increased
      Bax protein expression in cisplatin-induced A549 cells by over-regulation of
      microRNA-133b. Altogether, our results indicated that over-regulation of microRNA
      133b inhibits cell proliferation of cisplatin-induced NSCLC by PI3K/Akt and
      JAK2/STAT3 signaling pathway by targeting EGFR.

PMID- 29344641
TI  - Inhibition of RPTOR overcomes resistance to EGFR inhibition in triple-negative
      breast cancer cells.
AB  - Triple-negative breast cancer (TNBC) cells frequently exhibit activated growth
      factor signaling and resistance to inhibitors for epidermal growth factor
      receptor (EGFR), despite the overexpression of EGFR protein, and this is
      associated with a malignant behavior and a poor prognosis. In this study, to
      elucidate the underlying mechanisms of resistance to EGFR inhibitor and identify
      inhibitors that exert a synergistic effect with EGFR inhibition, we examined the
      inhibitory effects of selected protein kinase inhibitors (PKIs) in combination
      with gefitinib on the viability of a mesenchymal stem-like (MSL) subtype TNBC
      cell line. MK-2206, an AKT inhibitor, and a group of mammalian target of
      rapamycin (mTOR) inhibitors were found to exert synergistic lethal effects in
      combination with gefitinib in MDA-MB-231 cells. The combination of gefitinib/MK
      2206 exerted a prominent synergistic lethal effect in an MTT cell viability assay
      and a growth inhibitory effect in a long-term colony-forming assay in 2 MSL
      subtype TNBC cell lines (MDA-MB-231 and HS578T) and one basal-like (BL) subtype
      TNBC cell line (MDA-MB-468). Gefitinib/MK-2206 treatment synergistically
      decreased the mTOR signaling target substrates along with the downregulation of
      ribosomal protein S6 (RPS6), a marker of cell proliferation and target substrate
      of the AKT-mTOR signaling pathway. In addition, gefitinib markedly reduced the
      viability of MDA-MD-231 and HS578T cells when regulatory-associated protein of
      mTOR (RPTOR) was suppressed by siRNA-based knockdown (KD). These results thus
      suggest that RPTOR mediates, at least partially, the resistance to EGFR
      inhibition in TNBC cells. Therefore, targeting the mTOR complex 1 (mTORC1)
      pathway may be a potential strategy for the treatment of EGFR-resistant TNBC.

PMID- 29344642
TI  - Microarray analysis reveals Tmub1 as a cell cycle-associated protein in rat
      hepatocytes.
AB  - Transmembrane and ubiquitin-like domain containing protein 1 (Tmub1), formerly
      known as hepatocyte odd protein shuttling (HOPS) has been recognized as a
      ubiquitously expressed shuttling protein that moves between the nucleus and
      cytoplasm in hepatocytes. Tmub1 is involved in liver regeneration and functions
      as a bridging protein in tumor cell proliferation. To investigate the
      transcriptional profile and potential biological processes affected by Tmub1
      expression in normal rat hepatocytes, microarray and bioinformatics experiments
      were used to identify 127 mRNAs differentially expressed between Tmub1
      overexpression, Tmub1-knockdown and normal BRL-3A cells (fold-change >=2.5). The
      expression levels of 17 key node genes associated with the cell cycle were
      confirmed by reverse transcription-quantitative polymerase chain reaction
      analysis. Flow cytometry, 5-Ethynyl-20-deoxyuridine, Cell Counting Kit-8 and
      western blotting experiments revealed the effects on the cell cycle and the
      inhibition of proliferation in BRL-3A cells overexpressing Tmub1. Further co
      immunoprecipitation assays demonstrated that Tmub1 interacts with cyclin A2
      during the cell cycle and that the overexpression of Tmub1 may postpone cyclin A2
      and cyclin B1 degradation in the M phase. The results of the present study
      indicated that Tmub1 functions as a cell proliferation inhibitor and cell cycle
      associated protein.

PMID- 29344643
TI  - MicroRNA-23a-5p regulates osteogenic differentiation of human bone marrow-derived
      mesenchymal stem cells by targeting mitogen-activated protein kinase-13.
AB  - The molecular mechanisms of osteogenic differentiation of bone marrow-derived
      mesenchymal stem cells (BMSCs) remain to be fully elucidated. MicroRNAs (miRs)
      serve vital roles in the process of regulating osteogenic differentiation of
      BMSCs. The present study aimed to investigate the role of miR-23a-5p in
      osteogenic differentiation of human (h)BMSCs, and the underlying molecular
      mechanism. The results of reverse transcription-quantitative polymerase chain
      reaction demonstrated that miR-23a-5p was significantly downregulated in the
      process of osteogenic differentiation. Upregulation of miR-23a-5p inhibited
      osteogenic differentiation of hBMSCs, and down-regulated expression of miR-23a-5p
      enhanced this process, which was confirmed by alkaline phosphatase (ALP) and
      Alizarin Red S staining. A dual-luciferase reporter assay confirmed that mitogen
      activated protein kinase 13 (MAPK13) was a direct target of miR-23a-5p. In
      addition, knockdown of MAPK13 inhibited osteogenic differentiation of hBMSCs,
      similar to the effect of upregulation of miR-23a-5p. Finally, the knockdown of
      MAPK13 also blocked the effect of miR-23a-5p in osteogenic differentiation of
      hBMSCs, which was also confirmed by ALP and Alizarin Red S staining. These
      results indicated that by targeting MAPK13, miR-23a-5p serves a vital role in
      osteogenic differentiation of hBMSCs, which may provide novel clinical treatments
      for bone injury however, further studies are required.

PMID- 29344645
TI  - Targeted disruption of adenosine kinase in myeloid monocyte cells increases
      osteoclastogenesis and bone resorption in mice.
AB  - Adenosine kinase (ADK) serves an important role in intracellular adenosine
      clearance via phosphorylating adenosine to AMP. The role of adenosine and its
      receptors in the maintenance of bone homeostasis is well studied, particularly in
      osteoclastogenesis and bone resorption; however, the function of ADK in bone
      metabolism is still unclear. In the present study, utilizing the cre/floxp
      recombination system, mice with conditional loss of ADK function in myeloid
      monocyte cells were used to assess the effect of ADK deficiency on bone
      metabolism. Mice were evaluated by means of gross observation and bone
      histomorphometric analysis. Ex vivo osteoclast differentiation and bone
      resorption were also examined using genetic deletion and pharmacologic inhibition
      of ADK in osteoclasts. Compared with control mice, the results of the present
      study demonstrate that adult mice lacking ADK in the myeloid monocyte cells had
      reduced body weight and nasoanal length. The results of bone histomorphometric
      analysis revealed that bone mass was significantly decreased and osteoclastic
      parameters were increased in the study mice. Furthermore, in vitro cell culture
      revealed that inhibition of ADK function promoted osteoclast differentiation and
      bone resorption. Osteoclast-associated gene expression, including tartrate
      resistant acid phosphatase, nuclear factor of activated T-cells, cytoplasmic 1,
      matrix metalloproteinase 9, Cathepsin K and calcitonin receptor, was also
      significantly increased. These results suggest that mice with ADK deficiency have
      reduced bone formation due to increased osteoclastogenesis and bone resorption.
      The present study provides further insight into the mechanism by which ADK serves
      a key role in bone metabolism.

PMID- 29344646
TI  - Engineered zinc-finger transcription factors inhibit the replication and
      transcription of HBV in vitro and in vivo.
AB  - In the present study, an artificial zinc-finger transcription factor eukaryotic
      expression vector specifically recognizing and binding to the hepatitis B virus
      (HBV) enhancer (Enh) was constructed, which inhibited the replication and
      expression of HBV DNA. The HBV EnhI-specific pcDNA3.1-artificial transcription
      factor (ATF) vector was successfully constructed, and then transformed or
      injected into HepG2.2.15 cells and HBV transgenic mice, respectively. The results
      demonstrated that the HBV EnhI (1,070-1,234 bp)-specific ATF significantly
      inhibited the replication and transcription of HBV DNA in vivo and in vitro. The
      HBV EnhI-specific ATF may be a meritorious component of progressive combination
      therapies for eliminating HBV DNA in infected patients. A radical cure for
      chronic HBV infection may become feasible by using this bioengineering
      technology.

PMID- 29344644
TI  - Inactivation of DNA-PK by knockdown DNA-PKcs or NU7441 impairs non-homologous end
      joining of radiation-induced double strand break repair.
AB  - The DNA-dependent protein kinase (DNA-PK) complex plays a pivotal role in non
      homologous end-joining (NHEJ) repair. We investigated the mechanism of NU7441, a
      highly selective DNA-PK inhibitor, in NHEJ-competent mouse embryonic fibroblast
      (MEF) cells and NHEJ-deficient cells and explored the feasibility of its
      application in radiosensitizing nasopharyngeal carcinoma (NPC) cells. We
      generated wild-type and DNA-PKcs-/- MEF cells. Clonogenic survival assays, flow
      cytometry, and immunoblotting were performed to study the effect of NU7441 on
      survival, cell cycle, and DNA repair. NU7441 profoundly radiosensitized wild-type
      MEF cells and SUNE-1 cells, but not DNA-PKcs-/- MEF cells. NU7441 significantly
      suppressed radiation-induced DSB repair post-irradiation through unrepaired and
      lethal DNA damage, the cell cycle arrest. The effect was associated with the
      activation of cell cycle checkpoints. The present study revealed a mechanism by
      which inhibition of DNA-PK sensitizes cells to irradiation suggesting that
      radiotherapy in combination with DNA-PK inhibitor is a promising paradigm for the
      management of NPC which merits further investigation.

PMID- 29344647
TI  - Autophagy regulates the degeneration of the auditory cortex through the AMPK-mTOR
      ULK1 signaling pathway.
AB  - Presbycusis is the most common sensory impairment associated with aging; however,
      the underlying molecular mechanism remains unclear. Autophagy has been
      demonstrated to serve a key role in diverse diseases; however, no studies have
      examined its function in central presbycusis. The aim of the present study was to
      investigate the changes of autophagy in the physiological processes of the
      auditory cortex and its role in the degeneration of the auditory cortex, as well
      as the related mechanisms using naturally aging rats and a D-galactose (D-gal)
      induced mimetic rat model of aging. The present study demonstrated that autophagy
      increased from 3 months to 15 months in the normal saline (NS) control group,
      while it decreased in the D-gal group. Compared with the age-matched NS group,
      the D-gal group demonstrated significantly increased levels of the autophagy
      related proteins, LC3 and Beclin 1 (BECN1) and the anti-apoptotic proteins B-cell
      lymphoma (BCL)2 and BCL-extra large (BCL-xL) at 3 months, with no obvious changes
      in cell apoptosis level and neuron ultrastructural morphology. However, LC3,
      BECN1, BCL2 and BCL-xL were decreased at 15 months in the D-gal group, with cell
      apoptosis significantly increased and substantial neuron degeneration.
      Additionally, 5' AMP-activated protein kinase (AMPK) activity was enhanced, and
      mechanistic target of rapamycin (mTOR) and ULK1 phosphorylation (Ser 757)
      activities were inhibited at 3 months compared with those of the NS group, while
      the opposite was observed at 9 and 15 months. The present results suggested that
      autophagy increases from young to adult and decreases at old age in the
      physiological processes of the auditory cortex, and has anti-apoptotic as well as
      anti-aging functions in the degeneration of the auditory cortex. Additionally,
      autophagy was regulated through AMPK activation and mTOR suppression, and
      impairment of autophagy may serve a key role in the degeneration of the auditory
      cortex, even in the pathogenesis of central presbycusis.

PMID- 29344648
TI  - Effect of midkine on gemcitabine resistance in biliary tract cancer.
AB  - Gemcitabine-based chemotherapy is one of the most effective and commonly used
      chemotherapeutic regimens for biliary tract cancer (BTC). However, development of
      resistance to this drug limits its efficacy. The present study aimed to explore
      the effects of midkine (MDK) on the resistance of BTC cells to gemcitabine. Cell
      viability and proliferation were measured by a Cell Counting Kit-8 assay and 5
      ethynyl-2'-deoxyuridine staining, respectively. Western blot analysis was used to
      detect the expression of E-cadherin and vimentin. The results indicated that BTC
      cell lines were more resistant to gemcitabine plus MDK compared with gemcitabine
      alone. In terms of the underlying mechanism, MDK promoted the epithelial to
      mesenchymal transition (EMT) of BTC cells and the enhancing effect of MDK on
      gemcitabine resistance was abrogated when the EMT was blocked with small
      interfering (si)RNA targeting Twist. In addition, MDK promoted the expression of
      Notch-1, while knockdown of Notch-1 by siRNA blocked the EMT process in the BTC
      cell lines. Taken together, these results indicated that MDK promoted gemcitabine
      resistance of BTC through inducing EMT via upregulating Notch-1. It was suggested
      that inhibition of the EMT is a promising strategy to overcome MDK-induced drug
      resistance.

PMID- 29344649
TI  - Effects of intrathecal bupivacaine on the NR2B/CaMKIIalpha/CREB signaling pathway
      in the rat lumbar spinal cord.
AB  - Neuraxial anesthesia produces an anesthetic-sparing, sedative effect. The
      mechanism underlying this effect potentially involves decreased spinal afferent
      input. However, the neurochemical mechanisms at the spinal level remain unknown.
      The N-methyl-D-aspartate receptor 2B subunit/calcium-calmodulin-dependent protein
      kinase II alpha/cAMP response element-binding protein (NR2B/CaMKIIalpha/CREB)
      signaling pathway serves an important role in regulating the transmittance of
      peripheral noxious stimulation to supraspinal regions in the process of
      nociception. The present study investigated the effects of intrathecal
      bupivacaine on the NR2B/CaMKIIalpha/CREB signaling pathway. Following
      catheterization, 36 male Sprague-Dawley rats were randomly assigned to a normal
      saline (NS) or bupivacaine treatment group, in which each rat intrathecally
      received 20 ul normal saline or 0.5% bupivacaine, respectively. The expression
      levels of NR2B, CaMKIIalpha/p-CaMKIIalpha, and CREB/phosphorylated (p)-CREB in
      the lumbar spinal cord were investigated by western blotting, reverse
      transcription-quantitative polymerase chain reaction and immunohistochemistry
      (IHC). Following bupivacaine treatment, western blot analysis demonstrated that
      the protein expression levels of NR2B, p-CaMKIIalpha, and p-CREB in the spinal
      cord were reduced by approximately 54, 56 and 33%, respectively, compared with NS
      control rats. Similar alterations in expression were observed by IHC analysis.
      Additionally, mRNA expression levels of NR2B, CaMKIIalpha, and CREB were also
      downregulated following the intrathecal administration of bupivacaine. Therefore,
      the sedative effect of subarachnoid blockade with bupivacaine possibly occurs
      through de-afferentation, which may reduce cortical arousal by downregulating the
      spinal NR2B/CaMKIIalpha/CREB pathway in vivo, however further investigation is
      required in order to verify this.

PMID- 29344650
TI  - Adrenomedullin serves a role in the humoral pathway of delayed remote ischemic
      preconditioning via a hypoxia-inducible factor-1alpha-associated mechanism.
AB  - Remote ischemic preconditioning (RIPC) is a minimally invasive method that
      provides protection by reducing injury to the heart, kidneys, brain and other
      tissues or organs. RIPC may improve the outcome in patients undergoing surgery.
      Although the role of RIPC has been studied, the results remain controversial. It
      is difficult to confirm whether RIPC has a kidney protective effect and the
      understanding of the preconditioning signal pathway involved remains unclear. In
      the present study, the effect of RIPC in urology was evaluated. The protection
      against renal damage was assessed by investigating the potential mediator,
      hypoxia-inducible factor-1alpha (HIF-1alpha), and the functional adrenomedullin
      (ADM) pathway. Male Sprague-Dawley (SD) rats were used in the present study. The
      animal model of kidney damage induced by ischemia reperfusion (IR) was used to
      investigate the protective effect of the acute and delayed phase RIPC.
      Furthermore, the protective effects of RIPC mediated by a HIF-1alpha-ADM pathway
      were assessed. The indexes of renal function and oxidative damage indicators were
      measured by Cr, BUN, mALB, beta2-MG, MPO, MDA and SOD assays, and the expression
      of HIF-1alpha and ADM were detected by western blot analysis,
      immunohistochemistry and ELISA assays. Tubular score, determined using
      hematoxylin and eosin staining, was used to evaluate renal tissue damage.
      Applying RIPC prevented IR-induced renal dysfunction and oxidative damage by
      decreasing Cr, BUN, mALB, beta2-MG, MPO, MDA levels and increasing SOD activity.
      Findings showed that delayed RIPC had an improved effect compared with acute
      treatment. Delayed RIPC also upregulated the expression of HIF-1alpha and ADM,
      indicating that the protective effect of the delayed RIPC may be associated with
      a HIF-1alpha-ADM-mediated mechanism. The effect of the delayed RIPC to reduce IR
      induced renal damage and increase ADM expression was enhanced by HIF-1alpha
      agonists DMOG and BAY 85-3934, whereas the effect was whittled by HIF-1alpha
      antagonists YC-1 and 2-MeOE2. Furthermore, receiving ADM also offered protection
      to the kidney in comparison with the IR+Vehicle group. These findings suggest
      that RIPC prevents IR-mediated renal damage by HIF-1alpha via an ADM humoral
      pathway. In the present study, RIPC provided an effective renal protection. ADM
      could also offer protection regulated by HIF-1alpha in renal tissue. However, the
      mechanism of ADM as a protective factor in RIPC requires further research.

PMID- 29344651
TI  - Identification of genes and pathways in the synovia of women with osteoarthritis
      by bioinformatics analysis.
AB  - Osteoarthritis (OA) has a high prevalence in female patients and sex may be a key
      factor affecting the progression of OA. The aim of the present study was to
      identify genetic signatures in the synovial membranes of female patients with OA
      and to elucidate the potential associated molecular mechanisms. The gene
      expression profiles of the GSE55457 and GSE55584 datasets were obtained from the
      Gene Expression Omnibus database. Data of two synovial membranes from normal
      female individuals (GSM1337306 and GSM1337310) and two synovial membranes from
      female patients affected by OA (GSM1337327 and GSM1337330) were obtained from the
      dataset GSE55457, and those of three synovial membranes from female patients
      affected by OA (GSM1339628, GSM1339629 and GSM1339632) were obtained from the
      dataset GSE55584. Differentially expressed genes (DEGs) were identified by using
      Morpheus software. Protein-protein interaction (PPI) networks of the DEGs were
      constructed by using Cytoscape software. Subsequently, Gene Ontology (GO)
      function and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment
      analyses of the top module of the PPI network were performed by using ClueGo. A
      total of 377 DEGs were identified in the synovial membranes of OA patients
      compared with those of normal individuals, including 164 upregulated and 213
      downregulated genes. The top 10 hub genes were ubiquitin (UB)C, ribosomal protein
      (RP) L23A, mammalian target of rapamycin, heat shock protein 90 alpha family
      class A member 1, RPS28, RPL37A, RPS24, RPS4X, RPS18 and UBB. The results of the
      GO analysis indicated that the DEGs included in the top module of the PPI were
      mainly enriched in the terms 'nuclear-transcribed mRNA catabolic process',
      'nonsense mediated decay', and 'cytoplasmic translation and ribosomal small
      subunit biogenesis'. KEGG pathway analysis indicated that the DEGs included in
      the top one module were mainly enriched in the 'ribosome' pathway. The present
      study provides a systematic, molecular-level understanding of the degeneration of
      the synovial membrane in the progression of OA in female patients. The hub genes
      and molecules associated with the synovial membrane may be used as biomarkers and
      therapeutic targets for the treatment of OA in female patients with OA.

PMID- 29344652
TI  - Chrysophanol inhibits proliferation and induces apoptosis through NF
      kappaB/cyclin D1 and NF-kappaB/Bcl-2 signaling cascade in breast cancer cell
      lines.
AB  - Chrysophanol is an anthraquinone compound, which exhibits anticancer effects on
      certain types of cancer cells. However, the effects of chrysophanol on human
      breast cancer remain to be elucidated. The aim of the present study was to
      clarify the role of chrysophanol on breast cancer cell lines MCF-7 and MDA-MB
      231, and to identify the signal transduction pathways regulated by chrysophanol.
      MTT assay and flow cytometric analysis demonstrated that chrysophanol inhibited
      cell proliferation, and cell cycle progression in a dose-dependent manner. The
      expression of cell cycle-associated cyclin D1 and cyclin E were downregulated
      while p27 expression was upregulated following chrysophanol treatment at the
      mRNA, and protein levels. The Annexin V/propidium iodide staining assay results
      revealed that apoptosis levels increased following chrysophanol treatment.
      Chrysophanol upregulated caspase 3 and poly (ADP-ribose) polymerase cleavage in
      both cell lines. Furthermore, chrysophanol enhanced the effect of paclitaxel on
      breast cancer cell apoptosis. In addition, chrysophanol downregulated apoptosis
      regulator Bcl-2 protein, and transcription factor p65 and IkappaB
      phosphorylation. Inhbition of nuclear factor (NF)-kappaB by ammonium pyrrolidine
      dithiocarbamate diminished the effect of chrysophanol on apoptosis and associated
      proteins. In conclusion, the results of the current study demonstrated that
      chrysophanol effectively suppresses breast cancer cell proliferation and
      facilitates chemosentivity through modulation of the NF-kappaB signaling pathway.

PMID- 29344653
TI  - A novel variant of osteogenesis imperfecta type IV and low serum phosphorus level
      caused by a Val94Asp mutation in COL1A1.
AB  - Osteogenesis imperfecta (OI) is a rare congenital disorder characterized by bone
      fragility and fractures, and associated with bone deformity, short stature,
      dentin, ligament and blue-gray eye sclera. OI is caused by a heterozygous
      mutation in collagen alpha-1(I) chain (COL1A1) or collagen alpha-2(I) chain
      (COL1A2) genes that encode alpha chains of type I collagen. Collagen alpha chain
      peptide contains an N-propeptide, which has a role in assembly and processing of
      collagen. Point mutations in the N-propeptide domain appear to trigger OI. In the
      present study, a novel heterozygous missense mutation, c.281T>A (p.Val94Asp), was
      identified in the von Willebrand C domain of N-terminal of type I collagen in an
      individual with type IV OI. The majority of N-terminal mutations are associated
      with OI/Ehlers-Danlos syndrome (EDS); however, in the present study, the affected
      individual did not suffer from EDS and the level of serum phosphorus of the
      patient was low (0.67 mmol/l). A number of clinical phenotypes were observed at
      the same variation site or in the same region on the polypeptide chain of COL1A,
      which suggests that additional genetic and environmental factors may influence
      the severity of OI. The present study may provide insight into the phenotype
      genotype association in collagen-associated diseases and improve clinical
      diagnosis of OI.

PMID- 29344654
TI  - Tunicamycin inhibits colon carcinoma growth and aggressiveness via modulation of
      the ERK-JNK-mediated AKT/mTOR signaling pathway.
AB  - Epidemiology and evidence have demonstrated that colon carcinoma is one of the
      most common gastrointestinal tumors in the clinic. Reports have suggested that
      Tunicamycin significantly inhibits aggressiveness of colon carcinoma cells by
      promotion of apoptosis. In the present study, the inhibitory effect of
      tunicamycin on colon cancer cells and the potential underlying molecular
      mechanism was investigated. Western blotting, immunohistochemistry, apoptotic
      assays and immunofluorescence were used to analyze the therapeutic effects of
      tunicamycin on apoptosis, growth, aggressiveness and cell cycle of colon tumor
      cells, by downregulation of fibronectin, vimentin and E-cadherin expression
      levels. In vitro experiments demonstrated that tunicamycin significantly
      inhibited growth, migration and invasion of colon carcinoma cells. In addition,
      tunicamycin administration promoted apoptosis of colon carcinoma cells via
      upregulation of apoptotic protease activating factor 1 and cytochrome c
      expression levels, which are proteins that have a role in mitochondrial apoptosis
      signaling. Cell cycle assays revealed that tunicamycin suppressed proliferation
      and arrested S phase entry of colon carcinoma cells. Mechanistic analysis
      demonstrated that tunicamycin reduced expression and phosphorylation levels of
      extracellular signal-regulated kinase (ERK), c-JUN N-terminal kinase (JNK) and
      protein kinase B (AKT), and inhibited mammalian target of rapamycin (mTOR)
      expression levels in colon carcinoma cells. Endogenous overexpression of ERK
      inhibited tunicamycin-mediated downregulation of JNK, AKT and mTOR expression,
      which further blocked tunicamycin-mediated inhibition of growth and
      aggressiveness of colon carcinoma. In vivo assays revealed that tunicamycin
      treatment significantly inhibited tumor growth and promoted apoptosis, which led
      to long-term survival of tumor-bearing mice compared with the control group. In
      conclusion, these results suggested that tunicamycin may inhibit growth and
      aggressiveness of colon cancer via the ERK-JNK-mediated AKT/mTOR signaling
      pathway, and suggested that tunicamycin may be a potential anti-cancer agent for
      colon carcinoma therapy.

PMID- 29344655
TI  - Protective effects of osthole against inflammation induced by lipopolysaccharide
      in BV2 cells.
AB  - Inflammation and oxidative stress are implicated in the development of
      neurodegenerative diseases. Osthole is a compound that is extracted from She
      Chuang Zi, which is a type of traditional Chinese medicine. Osthole has
      previously been demonstrated to exhibit anticancer activities and has a low
      toxicity. However, to the best of our knowledge, the anti-inflammatory effects of
      osthole in microglial cells have not been investigated extensively. The aim of
      the present study was to investigate the potential protective effects of osthole
      against inflammation induced by lipopolysaccharide (LPS) in microglial cells. The
      present study employed LPS-stimulated BV2 mouse microglia to establish an
      inflammatory cell model and to investigate the anti-inflammatory effects of
      osthole. Cells were pretreated with osthole for 1 h prior to LPS (10 ug/ml)
      stimulation. At 6 h after the addition of LPS, alterations in the levels of
      inflammatory factors, including tumor necrosis factor (TNF)-alpha, interleukin
      (IL)-6 and IL-1beta, were determined by ELISA. Furthermore, at 24 h after the
      addition of LPS, western blot analysis was performed to analyze the alterations
      in the protein expression of nuclear factor-kappaB (NF-kappaB) p65,
      phosphorylated-NF-kappaB p65, nuclear factor erythroid 2-related factor 2 (Nrf2)
      and heme oxygenase (HO)-1. The results demonstrated that the secretion of the
      inflammatory cytokines TNF-alpha, IL-6 and IL-1beta by LPS-stimulated BV2 cells
      was significantly reduced by osthole treatment. Simultaneously, osthole treatment
      inhibited the LPS-induced activation of the NF-kappaB signaling pathway. In
      addition, osthole upregulated the expression of Nrf2 and HO-1 in a dose-dependent
      manner. Based on these results, osthole may exhibit anti-inflammatory effects via
      the NF-kappaB and Nrf2 pathways, indicating that osthole has the potential to be
      developed into an effective anti-inflammatory drug.

PMID- 29344656
TI  - Liraglutide suppresses proliferation and induces adipogenic differentiation of
      3T3-L1 cells via the Hippo-YAP signaling pathway.
AB  - Liraglutide, as a glucagon-like peptide-1 analogue, is used to treat type 2
      diabetes mellitus and obesity. Previous findings have demonstrated the effects of
      liraglutide on adipogenesis; however, the underlying mechanism involved in this
      process remains to be elucidated. In the present study, to certify the effect of
      liraglutide on adipogenesis and explore the possible underlying mechanism
      involved in this process, preadipocyte 3T3-L1 cells were cultured in adipocyte
      inducing medium and treated with liraglutide. Subsequently, the expression levels
      of the master transcription factors and adipocyte-specific genes were measured by
      reverse transcription-quantitative polymerase chain reaction and immunoblotting
      analysis. Lipid droplet production was detected by Oil red O staining. Cell
      proliferation was determined by a Cell Counting Kit-8 assay and cell
      immunofluorescence for Ki67, and apoptosis was assessed by flow cytometry. Next,
      the expression levels of the core components in the Hippo-yes-associated protein
      (YAP) signaling pathway as well as YAP-specific target genes were measured.
      Finally, short interfering RNAs of mammalian ste20 kinase 1/2 (MST1/2), a key
      protein kinase in the Hippo-YAP pathway, were used to determine whether
      liraglutide regulated adipogenic differentiation via the Hippo-YAP pathway. It
      was demonstrated that liraglutide promoted adipogenic differentiation, suppressed
      proliferation, did not affect apoptosis of 3T3-L1 cells and activated the Hippo
      YAP signaling pathway at the initial stage of adipogenesis. Silencing of MST1
      counteracted the effect of increasing adipogenesis by liraglutide. These results
      suggested that liraglutide may activate the Hippo-YAP signaling pathway leading
      to the inhibition of proliferation of preadipocyte 3T3-L1 cells, and result in
      cells achieving transformation into mature adipocytes sooner. Taken together, the
      results of the present study may expand knowledge of the underlying mechanism of
      liraglutide facilitating adipogenesis, and may contribute to the development of
      GLP-1 receptor agonists for weight loss and increased insulin sensitivity.

PMID- 29344657
TI  - Effects of hereditary moderate high fat diet on metabolic performance and
      physical endurance capacity in C57BL/6 offspring.
AB  - Obesity in pregnant women presents a risk to fetal health, leading to numerous
      metabolic syndromes and chronic inflammation risks. Previously, physical exercise
      was considered to be one of the primary treatments for obesity. However, the
      effect of fat consumption throughout the life cycle on physical endurance
      capacity remains unknown. A total of two groups of female mice (age, 6 weeks;
      C57BL/6J) were fed with a normal chow diet and a moderate high fat diet (MHFD),
      during pregnancy and lactation (8 weeks), with the offspring receiving the same
      diet as the mother. When filial mice were 8, 16 and 24 weeks old, they were
      tested for endurance, blood pressure (BP) and glucose tolerance, as well as
      adipose tissue infiltration and macrophage subtype. Compared with the control
      group, filial mice in MHFD groups exhibited increased BP and glucose levels and
      larger adipose cells (~4-fold). During adolescence, the obese filial mice
      demonstrated increased endurance compared with controls. Endurance declines in
      middle and old age; the endurance of aged obese mice was 29% that of lean ones.
      In addition, body coordination and movement memory did not notably change. The
      expression of cluster of differentiation 68, one of the most reliable markers of
      macrophages, increased by 2.48-fold, demonstrating that macrophages were
      recruited and underwent infiltration. In addition, increased tumor necrosis
      factor-alpha and decreased interleukin-10 expression demonstrated that
      infiltrated macrophages are polarized to the M1 state, which weakens physical
      endurance and resists type M2 macrophages, which exhibit repairing functions. In
      conclusion, hereditary MHFD weakens physical endurance and alters the metabolic
      characteristics of C57BL/6 offspring.

PMID- 29344658
TI  - MicroRNA-188-3p is involved in sevoflurane anesthesia-induced neuroapoptosis by
      targeting MDM2.
AB  - Sevoflurane is a commonly used inhalation anesthetic. Sevoflurane-induced
      neuroapoptosis and cognitive impairments in animals are widely reported, however,
      the underlying molecular mechanisms remain largely unknown. The results of the
      present study demonstrated that sevoflurane anesthesia induced spatial memory
      impairments in rats, as determined by the Morris water maze test.
      Mechanistically, the current study demonstrated that sevoflurane administration
      significantly enhanced the expression of microRNA (miR)-188-3p. Furthermore,
      inhibition of miR-188-3p using lentiviral miR-188-3p inhibitors attenuated
      sevoflurane-induced cognitive impairments in rats. The present study also
      demonstrated that miR-188-3p targeted MDM2 proto-oncogene (MDM2) and negatively
      regulated the expression of MDM2, as determined by luciferase assays, reverse
      transcription-quantitative polymerase chain reaction and western blot analysis.
      Furthermore, decreased abundance of MDM2 following transfection with miR-188-3p
      mimics was associated with increased stability of p53 protein. Suppression of p53
      activity using the specific p53 inhibitor pifithrin-alpha alleviated sevoflurane
      induced neuroapoptosis. These results indicate that the miR-188-3p-MDM2-p53 axis
      may have a critical role in sevoflurane-induced cognitive dysfunction. Therefore,
      miR-188-3p may be a potential target for the treatment of sevoflurane-induced
      cognitive impairment.

PMID- 29344659
TI  - Degree of endplate chondrocyte degeneration in different tension regions during
      mechanical stimulation.
AB  - The aim of this study was to explore the degree of degeneration of endplate
      chondrocytes in different tension regions induced by intermittent cyclic
      mechanical tension (ICMT) in vitro. Rat endplate chondrocytes were harvested and
      treated with 10% ICMT for 8 h/day with a frequency of 0.5 Hz. A cartilage
      degeneration model was induced using an FX-5000T cell strain-loading system. The
      experiment was divided into the central region and the peripheral region,
      according to the contact area between the loading post and the six-well flexible
      silicone rubber BioFlex plates. Toluidine blue and phalloidin staining were used
      to observe the morphological changes of cells following mechanical stimulation.
      Apoptosis was detected by flow cytometry and the mRNA and protein expression
      levels of collagen type II alpha1, aggrecan, SRY-box 9 and matrix
      metalloproteinase 13 were detected by reverse transcription-quantitative
      polymerase chain reaction (RT-qPCR) and western blotting, respectively. Endplate
      chondrocytes exhibited degenerative alterations under mechanical conditions of
      10% ICMT and 0.5 Hz at 8 h/day. Toluidine blue and phalloidin staining
      demonstrated that the cells in the peripheral region were more slender compared
      with cells in the central region, but RT-qPCR and western blotting results
      demonstrated that the degree of cell degeneration between the two groups was not
      statistically differences. So that cell morphological alteration does not imply
      that cells have undergone degeneration.

PMID- 29344660
TI  - Purple sweet potato color attenuates high fat-induced neuroinflammation in mouse
      brain by inhibiting MAPK and NF-kappaB activation.
AB  - Purple sweet potato color (PSPC) is a natural anthocyanin pigment that is derived
      from purple sweet potato storage roots. PSPC possesses a variety of biological
      activities, including antioxidant, anti-inflammatory and neuroprotective effects;
      however, the detailed effects of PSPC on high-fat diet (HFD)-induced
      neuroinflammation remain to be determined. The aim of the present study was to
      investigate whether PSPC has a protective role in HFD-associated
      neuroinflammation in the mouse brain and to provide novel insight into the
      mechanisms of the action. C57BL 6J mice were maintained on a normal diet (10
      kcal% fat), a HFD (60 kcal% fat), a HFD with PSPC (700 mg/kg/day) or PSPC alone,
      which was administrated over 20 weeks. Open field and step-through tests were
      used to evaluate the effects of HFD and PSPC on mouse behavior and memory
      function. Western blotting and ELISA analyses were used to assess the expression
      of inflammatory cytokines and the activation of mitogen-activated protein kinase
      and nuclear factor-kappaB (NF-kappaB). The results demonstrated that PSPC
      treatment was able to significantly improve the HFD-induced impairment of mouse
      behavior and memory function, and suppressed the increase in body weight, fat
      content, hyperlipemia and the level of endotoxin. PSPC treatment also markedly
      decreased the expression of cyclooxygenase-2, inducible nitric oxide synthase,
      tumor necrosis factor-alpha, interleukin (IL)-1beta and IL-6, and increased the
      level of IL-10 in the HFD-treated mouse brain. In addition, PSPC inhibited the
      HFD-induced phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun
      N-terminal kinase (JNK) and p38, and the activation of NF-kappaB. These findings
      indicated that PSPC treatment may alleviate HFD-induced neuroinflammation in the
      mouse brain by inhibiting ERK, JNK, p38 and NF-kappaB activation.

PMID- 29344661
TI  - Plasma levels of microRNA-21, -126 and -423-5p alter during clinical improvement
      and are associated with the prognosis of acute heart failure.
AB  - MicroRNAs are associated with myocardial damage and heart failure (HF). The
      present study investigated whether the plasma levels of microRNA (miR)-21, -126
      and -423-5p alter according to the (de)compensated state of patients with HF and
      are associated with all-cause mortality. In 48 patients with HF admitted to the
      emergency room for an episode of acute decompensation, blood samples were
      collected to measure miR and B-type natriuretic peptide levels within 24 h of
      hospital admission, at the time of hospital discharge, and a number of weeks post
      discharge (chronic stable compensated state). Levels of miR-21, miR-126 and miR
      423-5p increased between admission and discharge, and decreased following
      clinical compensation. During follow-up (up to 48 months), 38 patients (79%) were
      rehospitalized at least once and 21 patients (44%) succumbed. Patients who had
      increased levels of miR-21 and miR-126 at the time of clinical compensation
      exhibited better 24-month survival and remained rehospitalization-free for a
      longer period compared with those with low levels. Additionally, patients whose
      levels of miR-423-5p increased between admission and clinical compensation
      experienced fewer hospital readmissions in the 24 months following the time of
      clinical compensation compared with those who had decreased levels. It was
      concluded that the plasma levels of miR-21, miR-126 and miR-423-5p altered during
      clinical improvement and were associated with the prognosis of acute
      decompensated HF.

PMID- 29344662
TI  - Dengue virus-1 NS5 genetic variant associated with a severe clinical infection:
      Possible reduction of the innate immune response by inhibition of interferon type
      1 and the Janus kinase-signal transducer and activator of transcription signaling
      pathway.
AB  - Dengue virus (DENV) is currently considered as one of the most important mosquito
      borne viral pathogens affecting humans. Genetic variations in viruses are likely
      to be a condition for more effective evasion of the immune system and resulting
      in severe clinical consequences. The DENV-1 NS5 gene was sequenced to establish
      whether during an epidemic burst there were genetic variations of the virus and
      whether any variant was associated (through a case-control design) with severe
      clinical behavior. A total of 31 patients positive for DENV-1 were enrolled.
      Among the nucleotide differences between the sequences, only two generated amino
      acid changes. The variants 124Met/166Ser (amino acid positions according to the
      report GenBank AJL35015.1), were associated with a severe clinical course of the
      disease. Via in silico tests, it was identified that the variations generate
      changes in the protein probably affecting the function of type-1 interferon,
      either at the level of its receptor or by interfering with the Janus kinase
      signal transducer and activator of transcription signaling pathway.

PMID- 29344663
TI  - Adeno-associated virus type 2-mediated gene transfer of a short hairpin-RNA
      targeting human IGFBP-2 suppresses the proliferation and invasion of MDA-MB-468
      cells.
AB  - Adeno-associated virus 2 (AAV2) is prepotent in the biological treatment of
      breast tumor because of its low pathogenicity and immunogenicity. Our previous
      study demonstrated that insulin-like growth factor-binding protein 2 (IGFBP-2)
      was highly expressed in patients with breast metastasis. In the present study,
      the effects of recombinant AAV2 on the growth and metastasis of breast cancer
      cells were determined in vitro, and in vivo. rAAV2-ZsGreen-shRNA-scramble and
      rAAV2-ZsGreen-shRNA-hIGFBP-2 were used to transfect MDA-MB-468, and MCF-10A cells
      respectively, and observed that these virus could not penetrate the normal human
      breast epithelia MCF-10A cell line. To investigate the effect of the recombinant
      virus on chemotherapeutics, paclitaxel was added to MDA-MB-468 cells and it was
      demonstrated that rAAV2-ZsGreen-shRNA-hIGFBP-2-infected MDA-MB-468 cells were
      highly chemosensitive to paclitaxel compared with rAAV2-ZsGreen-shRNA-scramble
      injected cells. In addition, it was demonstrated that the invasive ability of
      rAAV2-ZsGreen-shRNA-hIGFBP-2-infected MDA-MB-468 cells was highly impaired
      compared with the rAAV2-ZsGreen-shRNA-scramble group. In the nude mice
      xenografts, the rAAV2-ZsGreen-shRNA-hIGFBP-2 injection inhibited tumor growth and
      Ki-67 expression was significantly downregulated compared with the scramble
      group. Following IGFBP-2 knockdown using rAAV2-ZsGreen-shRNA-hIGFBP-2, matrix
      metalloproteinase-2 expression was significantly reduced in tumor tissues
      compared with that in rAAV2-ZsGreen-shRNA-scramble treated tumor tissues. These
      findings have provided a direction for the application of novel AAV2-based
      therapeutics for treating aggressive triple-negative breast cancer types.

PMID- 29344665
TI  - Overexpression of septin-7 inhibits melatonin-induced cell apoptosis in human
      fetal osteoblastic cells via suppression of endoplasmic reticulum stress.
AB  - Our previous study demonstrated that melatonin could induce apoptosis in the
      human fetal osteoblastic (hFOB) 1.19 cell line via induction of endoplasmic
      reticulum stress (ERS), and recent studies have demonstrated that the expression
      of septin-7 (SEPT7) exhibits a positive correlation with the concentration of
      melatonin. Western blotting demonstrated the expression level of SEPT7 was
      significantly upregulated in a dose-dependent manner following treatment with
      differing concentrations of melatonin compared with the control groups, which did
      not receive any treatment. The expression of proteins associated with cell
      apoptosis and endoplasmic reticulum stress (ERS; pro-caspase-3, cleaved caspase
      3, C/EBP-homologous protein, 78 kDa glucose-regulated protein and phosphorylated
      eukaryotic translation initiation factor 2alpha) were decreased following
      transfection with SEPT7 overexpression plasmid and increased following
      transfection with SEPT7 small interfering RNA compared with the control groups.
      The results of the present study suggest that SEPT7 inhibits melatonin-induced
      cell apoptosis via suppression of ERS.

PMID- 29344664
TI  - Crucial role of OX40/OX40L signaling in a murine model of asthma.
AB  - The aim of the present study was to explore the roles of OX40/OX40 ligand (OX40L)
      signaling and OX40+ T cells in ovalbumin (OVA)-induced mouse asthma model. Asthma
      was induced by OVA exposure and subsequent co-treatment with OX40L protein,
      neutralizing anti-OX40L blocking antibody, OX40+ T cells or PBS. The protein
      expression levels of interleukin (IL)-4, IL-6, IL-13, IL-17, tumor necrosis
      factor (TNF)-alpha and interferon (IFN)-gamma in bronchoalveolar lavage fluid
      (BALF) were examined using murine cytokine-specific ELISA. Eosinophil
      accumulation as well as proliferation and apoptosis of T cells in BALF were
      detected by Cell Counting kit-8 and flow cytometric assays. Expression of the
      apoptosis-related protein cleaved caspase-3 was examined in OX40+ T cells using
      western blot assay. Flow cytometric analysis revealed that OVA-treated mice that
      were co-treated with OX40L or OX40+ T cells exhibited higher eosinophil
      infiltration compared with control mice treated only with OVA, whereas
      neutralizing anti-OX40L blocking antibody inhibited eosinophil infiltration.
      ELISA assays demonstrated that the expression of IL-4, IL-6, IL-13, IL-17, TNF
      alpha and IFN-gamma in BALF in OX40L-treated and OX40+ T cell-treated mice was
      increased compared with expression levels in control mice. Treatment with OX40L
      protein effectively reduced apoptosis of T cells and the expression of cleaved
      caspase-3 in T cells. OX40L-treated and OX40+ T cell-treated mice exhibited
      increased asthma through OX40/OX40L signaling, which probably promoted
      inflammatory factor expression, eosinophil infiltration and T cell proliferation.

PMID- 29344666
TI  - Let-7b regulates alpaca hair growth by downregulating ectodysplasin A.
AB  - Hypohidrotic ectodermal dysplasia (HED), also known as anhidrotic ectodermal
      dysplasia, is characterized by the clinical manifestations of less sweat or no
      sweat, sparse or no hair, tooth agenesis and/or abnormal tooth morphology. The
      characteristics of alpaca ear hair differ from the back hair. The ectodysplasin A
      (EDA) signaling pathway has a regulatory effect on skin development and hair
      growth. The aim of the present study was to study the effects of EDA on alpaca
      hair growth by examining the mRNA and protein expression levels of EDA in alpaca
      ear and back skin by reverse transcription-quantitative polymerase chain reaction
      and western blot analysis, respectively. Results indicated that EDA expression
      was higher in the ear skin compared with the back skin. The expression levels of
      let-7b in the skin of healthy alpacas varies; the difference between let-7b
      expression levels of the ear and back have been reported to be >2-fold,
      suggesting a role for let-7b in the development of adult alpaca skin and hair
      follicles. A dual-luciferase reporter vector was constructed to verify the
      targeting relationship between microRNA let-7b and EDA, and the results revealed
      that EDA was a target gene of let-7b. Alpaca skin fibroblasts were transfected
      with a let-7b eukaryotic expression vector to investigate the regulatory
      relationship between let-7b and EDA. The expression of EDA was decreased in the
      transfected group; immunocytochemical results demonstrated that the EDA protein
      was abundantly expressed in the fibroblast cytoplasm. EDA protein expression was
      weaker in the transfected cells than in the untransfected cells. These results
      suggested that EDA may serve a role in alpaca hair growth and is probably a
      target gene of let-7b; let-7b downregulated EDA mRNA and protein expressions,
      which suggested that let-7b may regulate alpaca hair growth. These conclusions
      suggested that let-7b may be associated with HED.

PMID- 29344667
TI  - Clinical evaluation of covered stents in the treatment of superficial femoral
      artery pseudoaneurysm in drug abusers.
AB  - The present study aimed to investigate the technical feasibility and initial
      clinical outcomes of a covered stent for the endovascular treatment of
      superficial femoral artery (SFA) pseudoaneurysm in drug abusers. A total of 29
      drug abuse patients with SFA pseudoaneurysm, as confirmed by color Doppler
      sonography, were enrolled to the present study between January 2012 and May 2014.
      All patients were treated percutaneously by implantation of a covered stent.
      Physical examination and lower extremity computed tomography angiography were
      performed at 1 and 9 months postoperation. Furthermore, the ankle-brachial index
      (ABI) of all patients was measured. The results indicated that placement of the
      covered stent was technically successful in all 29 patients. All of the ruptured
      pseudoaneurysms were successfully sealed with no cases of intraprocedural
      mortality. In addition, all patients' conditions improved rapidly; active
      hemorrhage subsidence and vascular bruit disappearance were immediately detected
      following implantation of the covered stent. During the follow-up period, pain
      was markedly alleviated and pulsatile mass was decreased as time increased. No
      complaints or complications were documented. A total of 9 months postoperation,
      pain and pulsatile mass were not detected. The patency rate of the stent was
      100%, and no migration, occlusion or infection was detected. In addition, the ABI
      was significantly improved, from 0.52+/-0.09 to 0.97+/-0.37 (P<0.01). In
      conclusion, the placement of a covered stent may be considered a promising
      approach to provide an effective, safe and minimally invasive option for the
      treatment of SFA pseudoaneurysm in drug abusers.

PMID- 29344668
TI  - Blocking of autocrine IGF-1 reduces viability of human umbilical cord mesenchymal
      stem cells via inhibition of the Akt/Gsk-3beta signaling pathway.
AB  - Human umbilical cord mesenchymal stem cells (hUCMSCs) are able to secrete growth
      factors, such as hepatocyte growth factor, vascular endothelial growth factor and
      insulin-like growth factor-1 (IGF-1). The secretion of these growth factors by
      transplanted hUCMSCs have been identified to stimulate the growth of the host
      cells in the target organs or tissues. The aim of the present study was to
      investigate the effect of autocrine IGF-1 on cell viability of hUCMSCs. The
      expression levels of IGF-1 and the IGF-1 receptor (IGF-1R) in hUCMSCs were
      identified using immunocytochemistry staining. In order to block autocrine IGF-1,
      hUCMSCs were treated with 5 ug/ml alphaIR-3, a specific IGF-1R antibody, for 24
      h. The cells cultured in medium without alphaIR-3 were used as the control group.
      Cell viability, apoptosis, cell cycle and the proliferation-associated proteins
      were quantified using an MTT assay, flow cytometry and western blotting. The
      findings of the present study revealed that IGF-1 and IGF-1R were positively
      expressed in hUCMSCs. Treatment with alphaIR-3 significantly reduced cell
      viability and increased apoptosis of hUCMSCs (P<0.01). Cell cycle analysis
      indicated that the number of cells in the G2/M phase was reduced in the alphaIR-3
      treated group compared with the control group. Western blotting revealed that the
      expression levels of phosphorylated (p)-protein kinase B (Akt), p-glycogen
      synthase kinase 3beta (GSK-3beta), p-p70 S6 kinase and cyclin D1 were markedly
      reduced and p21 expression was markedly increased in the alphaIR-3-treated group
      as compared with the control group (P<0.05). However, no significant difference
      was identified in the p-extracellular-signal regulated kinase 1/2 expression when
      the alphaIR-3 treatment group was compared with the control group. (P>0.05). The
      findings of the present study suggested that the autocrine IGF-1 from hUCMSCs may
      be capable of influencing cell viability of hUCMSCs, which may be associated with
      activation of Akt/GSK-3beta signaling pathway.

PMID- 29344669
TI  - CLC-2 is a positive modulator of oligodendrocyte precursor cell differentiation
      and myelination.
AB  - Oligodendrocytes (OLs) are myelin-forming cells that are present within the
      central nervous system. Impaired oligodendrocyte precursor cell (OPC)
      differentiation into mature OLs is a major cause of demyelination diseases.
      Therefore, identifying the underlying molecular mechanisms of OPC differentiation
      is crucial to understand the processes of myelination and demyelination. It has
      been acknowledged that various extrinsic and intrinsic factors are involved in
      the control of OPC differentiation; however, the function of ion channels,
      particularly the voltage-gated chloride channel (CLC), in OPC differentiation and
      myelination are not fully understood. The present study demonstrated that CLC-2
      may be a positive modulator of OPC differentiation and myelination. Western
      blotting results revealed that CLC-2 was expressed in both OPCs and OLs.
      Furthermore, CLC-2 currents (ICLC-2) were recorded in both types of cells. The
      inhibition of ICLC-2 by GaTx2, a blocker of CLC-2, was demonstrated to be higher
      in OPCs compared with OLs, indicating that CLC-2 may serve a role in OL
      differentiation. The results of western blotting and immunofluorescence staining
      also demonstrated that the expression levels of myelin basic protein were reduced
      following GaTx2 treatment, indicating that the differentiation of OPCs into OLs
      was inhibited following CLC-2 inhibition. In addition, following western blot
      analysis, it was also demonstrated that the protein expression of the myelin
      proteins yin yang 1, myelin regulatory factor, Smad-interacting protein 1 and sex
      determining region Y-box 10 were regulated by CLC-2 inhibition. Taken together,
      the results of the present study indicate that CLC-2 may be a positive regulator
      of OPC differentiation and able to contribute to myelin formation and repair in
      myelin-associated diseases by controlling the number and open state of CLC-2
      channels.

PMID- 29344670
TI  - PGC-1alpha ameliorates kidney fibrosis in mice with diabetic kidney disease
      through an antioxidative mechanism.
AB  - The production of reactive oxygen species (ROS) is a common phenomenon in
      podocyte impairment, which leads to the irreversible progression of chronic
      kidney diseases, such as diabetic kidney disease (DKD). Previous research has
      indicated that peroxisome proliferator-activated receptor gamma (PPARgamma)
      coactivator-1alpha (PGC-1alpha) participates in mitochondrial biogenesis and
      energy metabolism in certain mitochondria-enriched cells, including myocardial
      and skeletal muscle cells. Therefore, we hypothesized that PGC-1alpha may be a
      protective nuclear factor against energy and oxidative stress in DKD. To
      investigate this hypothesis, db/db diabetic mice were used to establish a DKD
      model and the PPARgamma agonist rosiglitazone was employed to induce PGC-1alpha
      expression in vivo. Additionally, immortalized mouse podocytes and SV40 MES 13
      renal mesangial cells were utilized for in vitro experiments. The expression
      levels of PGC-1alpha and genes associated with kidney and cell injury were
      determined by western blotting or reverse transcription-quantitative polymerase
      chain reaction and intracellular ROS levels were assessed by 2',7'
      dichlorodihydrofluorescein diacetate. The results of the present study
      demonstrated that endogenous PGC-1alpha expression exhibited protective effects
      against oxidative stress, glomerulosclerosis and tubulointerstitial fibrosis in
      experimental DKD. These results indicated a potential role of PGC-1alpha in the
      amelioration of key pathophysiological features of DKD and provided evidence for
      PGC-1alpha as a potential therapeutic target in DKD.

PMID- 29344671
TI  - Role of miR-34c in the cognitive function of epileptic rats induced by
      pentylenetetrazol.
AB  - Studies suggest that microRNA (miR)-34c may serve a role in cognitive function in
      rodent and primate groups. A previous study demonstrated an increase in miR-34c
      expression in chronic epileptic rats with memory disorders, induced by
      pentylenetetrazol (PTZ). However, the mechanism underlying the effects of miR-34c
      on cognitive function in epileptic rats remains unclear. Therefore, the present
      study investigated alterations in cognitive function in temporal lobe epileptic
      rats, induced by repeated injections of PTZ, following treatment with an miR-34c
      agomir compared with a scramble group. Increased expression of miR-34c was
      observed in the agomir group, in addition to an increased deficit in learning and
      memory function in the Morris water maze test. Glutamate receptor ionotropic N
      methyl-D-aspartate (NMDA) 2B (NR2B), phosphorylated (p)-reduced nicotinamide
      adenine dinucleotide phosphate-dependent diflavin oxidoreductase 1 (NR1) and p
      glutamate receptor 1 (GluR1) protein expression was detected in the hippocampus
      using western blotting. Additionally, the downregulation of NR2B, p-NR1 and p
      GluR1 in the miR-34c agomir group demonstrated that miR-34c may serve a negative
      role in cognitive function in epileptic seizures, by dysregulating NMDA and alpha
      amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors, which are
      associated with long-term potentiation.

PMID- 29344672
TI  - Histone deacetylase inhibitor trichostatin A and autophagy inhibitor chloroquine
      synergistically exert anti-tumor activity in H-ras transformed breast epithelial
      cells.
AB  - Histone deacetylase inhibitors (HDACIs) cause oncogene-transformed mammalian cell
      death. Our previous study indicated that HDACIs activate forkhead box O1 (FOXO1)
      and induce autophagy in liver and colon cancer cells. However, whether FOXO1 is
      involved in HDACI-mediated oncogene-transformed mammalian cell death remains
      unclear. In the present study, H-ras transformed MCF10A cells were used to
      investigate the role of FOXO1 in this pathway. Results showed that trichostatin A
      (TSA), a HDACI, activated apoptosis in MCF10A-ras cells, but not in MCF10A cells.
      Furthermore, TSA activated FOXO1 via P21 upregulation, whereas the knockdown of
      FOXO1 reduced TSA-induced cell death. In addition, TSA induced autophagy in
      MCF10A and MCF10A-ras cells by blocking the mammailian target of rapamycin
      signaling pathway. Furthermore, autophagy inhibition lead to higher MCF10A-ras
      cell death by TSA, thus indicating that autophagy is essential in cell survival.
      Taken together, the present study demonstrated that TSA causes oncogene
      transformed cell apoptosis via activation of FOXO1 and HDACI-mediated autophagy
      induction, which served as important cell survival mechanisms. Notably, the
      present findings imply that a combination of HDACIs and autophagy inhibitors
      produce a synergistic anticancer effect.

PMID- 29344673
TI  - GOLPH2, a gene downstream of ras signaling, promotes the progression of
      pancreatic ductal adenocarcinoma.
AB  - Various studies have previously demonstrated that Golgi protein-73 (GOLPH2) is
      overexpressed in tumorigenesis, which has been observed in hepatocellular
      carcinoma and prostate cancer. However, the expression levels and specific
      functions of GOLPH2 in the progression of pancreatic cancer remain to be
      elucidated. The present study aimed to investigate the expression of GOLPH2 in
      pancreatic ductal adenocarcinoma (PDAC) tissues and examined the effects of
      GOLPH2 on the growth and migration of pancreatic cancer cells. In the present
      study, the mRNA levels of GOLPH2 in PDAC cancer tissues were examined using RT
      qPCR. The effects of GOLPH2 on the growth and migration of cancer cells were
      examined using crystal violet and Boyden chamber assays. The study demonstrated
      that the expression of GOLPH2 mRNA and protein was elevated in PDAC clinical
      tissues. The growth and motility of the PDAC cells was enhanced following
      overexpression of GOLPH2, whereas downregulating the expression of GOLPH2
      impaired the growth, motility and tumorigenesis. Furthermore, GOLPH2 was observed
      to interact with protein kinase B (Akt), which subsequently increased the
      activity of Akt. In addition, GOLPH2 was revealed as a downstream gene of Ras
      signaling and promoted the transformation of normal pancreatic cells. The results
      of the present study revealed the important functions of GOLPH2 in PDAC, and
      suggest that GOLPH2 may act as a promising therapeutic target for the treatment
      of PDAC in the future.

PMID- 29344674
TI  - Long non-coding RNA H1 promotes cell proliferation and invasion by acting as a
      ceRNA of miR-138 and releasing EZH2 in oral squamous cell carcinoma.
AB  - Long non-coding RNAs (lncRNAs) have been shown to play pivotal roles in various
      types of human cancer, including oral squamous cell carcinoma (OSCC). However,
      the potential mechanisms of action of lncRNAs in OSCC remain to be fully
      elucidated. The aim of the present study was to further explore the potential
      mechanisms of action of lncRNAs in OSCC. We first analyzed Gene Expression
      Omnibus (GEO) datasets to investigate aberrantly expressed lncRNAs which may be
      involved in the development of OSCC. Reverse transcription-quantitative PCR (RT
      qPCR) was performed to analyze the expression levels of lncRNA H19. In addition,
      the correlation between H19 expression and the clinical characteristics and
      prognosis of patients with OSCC was statistically analyzed. The effects of H19
      expression on OSCC cells were examined by using overexpression and RNA
      interference approaches in vitro and in vivo. To examine the competitive
      endogenous RNA (ceRNA) mechanisms, bioinformatics analysis and luciferase
      reporter assay were performed. In addition, the correlation between H19 and
      microRNA (miR)-138 was detected. H19 was found to be upregulated in OSCC tissues
      and its high expression level was associated with the TNM stage and nodal
      invasion, and also correlated with a shorter overall survival of patients with
      OSCC. The knockdown of H19 significantly inhibited OSCC cell proliferation,
      migration, invasion and epithelial-mesenchymal transition (EMT), and induced
      apoptosis in vitro; it also suppressed subcutaneous tumor growth in vivo. In
      addition, H19 was found to regulate the expression of oncogene enhancer of zeste
      homolog 2 (EZH2) by competing with miR-138; the inhibition of miR-138 attenuated
      the inhibitory effects of H19 knockdown on OSCC cells. On the whole, our findings
      suggest that H19 functions as an oncogene by inhibiting miR-138 and facilitating
      EZH2 expression in OSCC. Thus, lncRNA H1 may represent a potential therapeutic
      target for OSCC.

PMID- 29344675
TI  - Expression and prognostic significance of TRPV6 in the development and
      progression of pancreatic cancer.
AB  - In this study, we aimed to clarify the expression and biological functions of
      TRPV6 in human pancreatic cancer (PC) tissue and pancreatic cancer (PC) cell
      lines. TRPV6 was up-regulated in the primary cancer tissues from pancreatic
      cancer (PC) patients. TRPV6 may regulate multiple proteins related to apoptosis,
      cell cycle and metastasis pathways. Silencing TRPV6 significantly inhibited
      invasion, proliferation and migration and induced apoptosis and cell cycle
      arrest. TRPV6 plays a promising role of an oncogene in pancreatic carcinogenesis
      and represents the new potential biomarker for PC.

PMID- 29344677
TI  - Is vitamin D deficiency a public health concern for low middle income countries?
      A systematic literature review.
AB  - PURPOSE: Vitamin D deficiency has been receiving increasing attention as a
      potential public health concern in low and lower-middle income countries (LMICs),
      of which there are currently 83. We aimed to conduct a comprehensive systematic
      literature review (SLR) of available data on vitamin D status and prevalence of
      vitamin D deficiency in all 83 LMICs. METHODS: We followed the general
      methodology for SLRs in the area of serum 25-hydroxyvitamin D. Highest priority
      was placed on identifying relevant population-based studies, followed by cross
      sectional studies, and to a lesser extent case-control studies. We adopted the
      public health convention that a prevalence of vitamin D deficiency (serum 25
      hydroxyvitamin D < 25/30 nmol/L) at > 20% in the entire population and/or at-risk
      population subgroups (infants, children, women of child-bearing age, pregnancy)
      constitutes a public health issue that may warrant intervention. RESULTS: Our SLR
      revealed that of the 83 LMICs, 65% (n = 54 countries) had no published studies
      with vitamin D data suitable for inclusion. Using data from the remaining third,
      a number of LMICs had evidence of excess burden of vitamin D deficiency in one or
      more population subgroup(s) using the above convention (Afghanistan, Pakistan,
      India, Tunisia and Mongolia) as well as possibly other LMICs, albeit with much
      more limited data. Several LMICs had no evidence of excess burden. CONCLUSION:
      Vitamin D deficiency is a public health issue in some, but certainly not all,
      LMICs. There is a clear need for targeting public health strategies for
      prevention of vitamin D deficiency in those LMICs with excess burden.

PMID- 29344676
TI  - Application of Genome Editing Techniques in Immunology.
AB  - The idea of using the effector immune cells to specifically fight cancer has
      recently evolved into an exciting concept of adoptive cell therapies. Indeed,
      genetically engineered T cells expressing on their surface recombinant, cancer
      targeted receptors have been shown to induce promising response in oncological
      patients. However, in addition to exogenous expression of such receptors, there
      is also a need for disruption of certain genes in the immune cells to achieve
      more potent disease-targeted actions, to produce universal chimeric antigen
      receptor-based therapies or to study the signaling pathways in detail. In this
      review, we present novel genetic engineering methods, mainly TALEN and
      CRISPR/Cas9 systems, that can be used for such purposes. These unique techniques
      may contribute to creating more successful immune therapies against cancer or
      prospectively other diseases as well.

PMID- 29344678
TI  - Conservative antibiotic treatment for acute uncomplicated appendicitis is
      feasible.
AB  - PURPOSE: Appendectomy versus conservative antibiotic treatment (CAT) for children
      with acute uncomplicated appendicitis (AUA) remains unresolved, with concerns
      regarding the practicality of CAT. We analyzed our center's experience with CAT
      for AUA, using a protocol with strict inclusion, exclusion and treatment
      criteria. METHODS: Non-randomized, prospective cohort study included all children
      admitted betwee 2014 and 2016, with clinical and laboratory tests suspicious for
      AUA. Data collected included clinical signs and symptoms; laboratory, ultrasound
      and pathology results. Follow-up was conducted through clinic visits, telephone
      conversations and national registry analysis. RESULTS: Included in CAT: 362
      children, 19 underwent appendectomy within 1-2 days. Overall, 75 were readmitted
      for recurrent acute appendicitis during 22 months (6-43) follow-up. Thirty were
      treated successfully with antibiotics a second time. The remaining 45 had
      appendectomy. Overall, 86.8% underwent CAT with no surgery. Histology of all
      recurrent AUA revealed no perforations. CONCLUSION: We confirm the feasibility of
      conservative management of AUA in children. A rigorous diagnostic plan with
      strict inclusion and exclusion criteria will lead to high success rate of CAT
      with a strong safety profile. CAT does not compete with surgery or render
      appendectomy unnecessary. It is a safe alternative to surgery in selected cases.

PMID- 29344679
TI  - Distribution and dynamic expression of serotonin and dopamine in the nervous
      system and ovary of Holothuria scabra during ovarian maturation.
AB  - In the present study, the distribution and dynamic expression of serotonin and
      dopamine in the nervous system and ovary of the sea cucumber, Holothuria scabra,
      during different ovarian stages were investigated. We found that serotonin
      immunoreactivity was more intense in the neurons and neuropils of the outer
      ectoneural part, the inner hyponeural part, and the wall of hyponeural canal of
      radial nerve cord during the mature stages of ovarian cycle, whereas dopamine
      immunoreactivity was detected at a higher intensity in these tissues during the
      early stages. Both neurotransmitters were detected in the ectoneural part of the
      nerve ring. In the ovary, serotonin intensity was more intense in the cytoplasm
      of late oocytes, while dopamine-immunoreactivity was more intense in the early
      stages. The changes in the levels serotonin in the radial nerve cord and oocytes
      are incremental towards the late stages of ovarian maturation. In contrast,
      dopamine levels in the nervous tissues and oocytes were more intense in early
      stages and became decremental towards the late stages. These findings suggest
      that serotonin and dopamine may have opposing effects on ovarian development in
      this sea cucumber species.

PMID- 29344680
TI  - Acute and long-term outcome of focal atrial tachycardia ablation in the real
      world: results of the german ablation registry.
AB  - INTRODUCTION: Catheter ablation of focal atrial tachycardia (FAT) can be a
      challenging procedure and results have been rarely described. The purpose of this
      study was to determine the characteristics and results of FAT ablation in the
      large cohort of the German Ablation Registry. METHODS: The German Ablation
      Registry is a nationwide prospective multicenter database including 12566
      patients who underwent an ablation procedure between 2007 and 2010. Among them
      431 (3.4%) underwent an FAT ablation and 413 patients with documented locations
      were analyzed. Patients were divided into three groups according to the FAT
      location: biatrial (BiA, n = 31, 7.5%), left atrial (LA, n = 110, 26.5%), and
      right atrial (RA, n = 272, 66%). RESULTS: Acute success rate was 84% (68 vs. 85
      vs. 85% in biA, LA, and RA, respectively, p = 0.038). 4.8% of patients had an
      early recurrence during hospitalization, most in biatrial location (p < 0.001).
      No major acute complication occurred. At 12 months, 81% were asymptomatic or
      improved. The incidence of major adverse cardiovascular and cerebrovascular
      events (MACCE) was 3.7%. Arrhythmia freedom without antiarrhythmic drugs was 58%
      and was lower in biA (34 vs. 56% in LA vs. 62% in RA, p = 0.019). Early
      recurrence during hospitalization was an outstanding predictive factor for
      recurrence during follow-up. CONCLUSION: In this large patient population, FAT
      ablation had a relatively high acute success rate with a low complication rate.
      During follow-up, the recurrence rate was high, particularly in biatrial
      location. This was frequently predicted by an early recurrence during
      hospitalization.

PMID- 29344681
TI  - Timing of blood transfusion and oncologic outcomes in patients treated with
      radical nephroureterectomy for upper tract urothelial carcinoma.
AB  - PURPOSE: To evaluate the impact of timing of blood transfusion in patients with
      upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy
      (RNU). METHODS: Outcomes of consecutive patients with UTUC treated with RNU were
      analyzed. Clinicopathologic factors were compared using Fisher's exact test or
      the Wilcoxon rank-sum test between patients who received any transfusion and no
      transfusion, and between patients receiving intraoperative transfusion only and
      patients receiving no transfusion. Cancer-specific and overall survival were
      estimated and multivariable analyses were performed to assess the impact of
      timing of transfusion on clinical outcomes. RESULTS: Among 402 patients included
      in this study, 71 (17.6%) patients received a transfusion at any point and 27
      (6.7%) patients received an intraoperative blood transfusion. Transfusion at any
      time, patient comorbidity, high grade, advanced stage, positive surgical margins,
      low preoperative hemoglobin, longer operative duration, and increased blood loss
      were significantly associated with cancer-specific survival (DSS) on univariable
      analysis (HR 1.85, 95% CI 1.20-2.85, p < 0.005). In the multivariable analysis,
      transfusion at any point was not a prognostic factor (HR 1.00, 95% CI 0.60-1.68,
      p = 0.99). When examining intraoperatively transfusion only, transfusion was
      significantly associated with DSS (HR 1.91, 95% CI 1.01-3.59, p = 0.045) but no
      longer significant in multivariable analysis (HR 0.72, 95% CI 0.32-1.65, p =
      0.440). CONCLUSIONS: Our study indicates that the administration of blood
      transfusion either intraoperatively or postoperatively is not associated with
      clinical or oncological outcomes in patients with upper tract urothelial
      carcinoma when adjusted for other factors in multivariable analysis. Further
      study is required.

PMID- 29344682
TI  - 68Ga-prostate specific membrane antigen (PSMA) positron emission tomography (PET)
      for primary staging of high-risk prostate cancer: a systematic review.
AB  - PURPOSE: To systematically review currently available data on 68Ga-prostate
      specific membrane antigen (PSMA) positron emission tomography (PET) used for the
      primary staging of high-risk prostate cancer. METHODS: We performed critical
      reviews of EMBASE, Web of Science (including MEDLINE) and Cochrane databases in
      October 2016 according to the Preferred Reporting Items for Systematic Review and
      Meta-analysis statement. We included studies that utilized 68Ga-PSMA PET for
      primary staging of prostate cancer. Quality was assessed using the Critical
      Appraisal Skills Programme checklist for diagnostic test studies. RESULTS:
      Following our systematic search strategy, 12 studies were included for
      assessment. These studies comprised a total of 322 patients who underwent 68Ga
      PSMA PET scanning for the purpose of primary staging. Only 5 of these studies
      included histopathologic correlation data. High variation in methodology and
      outcomes such as sensitivity (range 33-99%) and specificity (> 90%) was seen
      across all studies. The ability of 68Ga-PSMA PET to detect malignant lesions was
      evident across studies, with most studies demonstrating increased detection rates
      with respect to conventional imaging modalities. CONCLUSIONS: In the primary
      staging of prostate cancer 68Ga-PSMA PET appears to outperform traditional
      imaging modalities. Overall, there are few high-quality studies investigating
      68Ga-PSMA PET in this sub-group highlighting the need for formal assessment of
      PSMA PET in the form of large-volume, prospective studies.

PMID- 29344684
TI  - Novel Injection Technique for Malar Cheek Volume Restoration.

PMID- 29344683
TI  - The root transcriptome of Achyranthes bidentata and the identification of the
      genes involved in the replanting benefit.
AB  - KEY MESSAGE: The transcriptome profiling in replanting roots revealed that
      expression pattern changes of key genes promoted important metabolism pathways,
      antioxidant and pathogen defense systems, adjusted phytohormone signaling and
      inhibited lignin biosynthesis. The yield of the medicinal plant Achyranthes
      bidentata could be significantly increased when replanted into a field cultivated
      previously for the same crop, but the biological basis of this so-called
      "replanting benefit" is unknown. Here, the RNA-seq technique was used to identify
      candidate genes responsible for the benefit. The analysis of RNA-seq libraries
      prepared from mRNA extracted from the roots of first year planting (normal
      growth, NG) and second year replanting (consecutive monoculture, CM) yielded
      about 40.22 GB sequencing data. After de novo assembly, 87,256 unigenes were
      generated with an average length of 1060 bp. Among these unigenes, 55,604 were
      annotated with public databases, and 52,346 encoding sequences and 2881
      transcription factors were identified. A contrast between the NG and CM libraries
      resulted in a set of 3899 differentially transcribed genes (DTGs). The DTGs
      related to the replanting benefit and their expression profiles were further
      analyzed by bioinformatics and qRT-PCR approaches. The major differences between
      the NG and CM transcriptomes included genes encoding products involved in
      glycolysis/gluconeogenesis, glutathione metabolism and antioxidant defense, in
      aspects of the plant/pathogen interaction, phytohormone signaling and
      phenylpropanoid biosynthesis. The indication was that replanting material enjoyed
      a stronger level of defense systems, a balance regulation of hormone signals and
      a suppression of lignin formation, thereby promoting root growth and development.
      The study provides considerable significant insights for a better understanding
      of the molecular mechanism of the replanting benefit and suggests their possible
      application in developing methods to reinforce the effects in medicinal plants.

PMID- 29344685
TI  - Long-Term Safety and Efficacy of Botulinum Toxin A Treatment in Adolescent
      Patients with Axillary Bromhidrosis.
AB  - BACKGROUND: For adolescent bromhidrosis, the long-term safety and efficacy of
      botulinum toxin type A (BTX-A) treatment are not clear to date. PATIENTS AND
      METHODS: From June 2011 to July 2016, 62 adolescent patients with primary
      axillary bromhidrosis were recruited and 50 U of BTX-A was administered in each
      axilla. Repetitive injections were performed when the malodor returned. RESULTS:
      The average follow-up was 2.64 years. There were no reported local or systemic
      adverse effects. After the first BTX-A injection, 61.3% of patients (38/62)
      maintained the duration of more than 4 weeks. Of these patients, 21 patients
      underwent two sessions, 8 patients underwent three sessions, and 4 patients
      underwent four sessions. Twenty-four of sixty-two (38.7%) of patients had the
      duration of < 4 weeks. The second injection with the same dose was immediately
      administered, and the resulting duration increased to 9 weeks. Nineteen patients
      received the third injection with 100 U per underarm, and the resulting duration
      was extended up to 16 weeks. Overall, 82% of patients (51/62) ranked the BTX-A
      treatment to be very good or good. CONCLUSION: For adolescent axillary
      bromhidrosis, BTX-A injection is safe and effective over a long-term follow-up.
      The duration of efficacy is variable, and the dosage should be fine-tuned based
      on the individual response. 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- 29344686
TI  - Executive control and faithfulness: only long-term romantic relationships require
      prefrontal control.
AB  - Individuals in the early stages of a romantic relationship generally express
      intense passionate love toward their partners. This observation allows us to
      hypothesize that the regulation of interest in extra-pair relationships by
      executive control, which is supported by the function of the prefrontal cortex,
      is less required in individuals in the early stages of a relationship than it is
      in those who are in a long-term relationship. To test this hypothesis, we asked
      male participants in romantic relationships to perform a go/no-go task during
      functional magnetic resonance imaging (fMRI), which is a well-validated task that
      can measure right ventrolateral prefrontal cortex (VLPFC) activity implicated in
      executive control. Subsequently, the participants engaged in a date-rating task
      in which they rated how much they wanted to date unfamiliar females. We found
      that individuals with higher right VLPFC activity better regulated their interest
      in dates with unfamiliar females. Importantly, this relationship was found only
      in individuals with long-term partners, but not in those with short-term
      partners, indicating that the active regulation of interest in extra-pair
      relationships is required only in individuals in a long-term relationship. Our
      findings extend previous findings on executive control in the maintenance of
      monogamous relationships by highlighting the role of the VLPFC, which varies
      according to the stage of the romantic relationship.

PMID- 29344687
TI  - Risk Factors for Early Postoperative Small Bowel Obstruction After Anterior
      Resection for Rectal Cancer: Methodological Issues: Reply.

PMID- 29344688
TI  - Inflammation-Based Prognostic Score Predicts Postoperative Survival of Patients
      with Interstitial Pneumonia After Undergoing Lung Cancer Resection.
AB  - OBJECTIVES: Idiopathic interstitial pneumonias (IIPs) are associated with an
      increased risk of lung cancer. Glasgow prognostic score (GPS), which uses serum C
      reactive protein (CRP) and albumin levels to indicate systemic inflammatory
      response and nutrition level, has been reported to be a predictor of overall
      survival in patients with various types of cancer. We evaluated the usefulness of
      GPS for prediction of survival of patients with both lung cancer and IIPs
      following a lung resection procedure. METHODS: Patients with IIPs who underwent
      lung cancer resection from January 2006 through December 2015 were investigated.
      Routine laboratory measurements, including serum CRP and albumin for determining
      GPS, were performed before the operation. Univariate and multivariate analyses
      with a COX proportional hazards regression model were used to identify
      independent risk factors for overall survival (OS), relapse-free survival (RFS),
      cancer-specific survival (CSS), and other disease-specific survival (ODSS).
      RESULTS: A total of 135 patients underwent lung resection during the study
      period. Multivariate analysis selected sublobar resection (p = 0.035), UIP
      pattern (p = 0.025), and GPS of 1-2 (p = 0.042) as predictive factors associated
      with OS, while GPS of 1-2 (p = 0.039) was shown to be a predictive factor
      associated with RFS. Multivariate analysis also revealed pTNM (p < 0.001), usual
      interstitial pneumonia pattern (p = 0.006), and GPS of 2 (p = 0.003) as
      predictive factors associated with CSS, while univariate analysis indicated pTNM
      (p = 0.042), GPS of 1 (p = 0.044), and %DLCO (p = 0.038) as predictive factors
      associated with ODSS. CONCLUSION: GPS is an independent prognostic factor of OS
      and RFS in lung cancer patients with IIPs undergoing a lung resection procedure.
      Furthermore, a GPS of 2 was found to be associated with CSS following lung cancer
      resection, while a score of 1 was associated with ODSS.

PMID- 29344689
TI  - Early Versus Late Tracheostomy in Trauma Patients: A Propensity-Matched Cohort
      Study of 5 Years' Data at a Single Institution in Korea.
AB  - BACKGROUND: Although there have been many studies dealing with tracheostomy
      timing in trauma patients, the optimal timing is still being debated. This study
      aimed to compare outcomes between early tracheostomy (ET) and late tracheostomy
      (LT) in trauma populations to estimate the optimal timing of tracheostomy after
      intubation. METHODS: We retrospectively reviewed the 5 years' data of trauma
      patients who underwent tracheostomy during their acute intensive care unit (ICU)
      stay. The cases were divided into two groups: ET was defined as tracheostomy
      performed within 7 days after intubation, and LT, after the seventh day.
      Propensity score matching was utilized using a 1-to-1 matching technique, and
      outcomes between two groups were compared. RESULTS: Among 236 enrolled patients,
      76 met the criteria for ET and 160 were included for LT. Using propensity
      matching, 70 patients who met the criteria for ET were matched to 70 patients in
      the LT. Based on the comparison of outcomes after matching, ET showed
      significantly shorter values than LT in overall ventilator duration, length of
      stay at the ICU, and post-tracheostomy ventilation duration. Furthermore, the
      incidence of pneumonia was significantly lower with ET than with LT, although the
      rate of postoperative complications showed no significant differences.
      CONCLUSIONS: We suggest that ET should be considered in trauma patients needing
      prolonged mechanical ventilation. Also, we recommend that surgeons perform
      tracheostomy as early as within 7 days after intubation to not only reduce the
      ventilation and ICU days but also prevent pneumonia without worrying about an
      increase in postoperative complications.

PMID- 29344690
TI  - [Globalization: challenges in abdominal surgery for migrants and refugees].
AB  - The increasing number of refugees, migrants and international travelers
      influences the surgical spectrum of abdominal diseases. The aim of this review is
      to familiarize surgeons with specific diseases which are endemic in the patients'
      countries of origin and are likely to be diagnosed with increasing incidence in
      Germany. Low levels of hygiene in the countries of origin or refugee camps is
      associated with a high incidence of numerous infections, such as helminth
      infections, typhoid fever or amoebiasis, which if untreated can cause surgical
      emergencies. Historically, some of them were common in Germany but have been more
      or less eradicated because of the high socioeconomic standard. Echinococcosis and
      Chagas disease are frequently treated surgically while schistosomiasis can mimic
      intestinal cancer. Abdominal tuberculosis presents in a variety of abdominal
      pathologies and frequently causes diagnostic uncertainty. Sigmoid volvulus has a
      very low incidence among Europeans, but is one of the most common abdominal
      surgical conditions of adults in endemic countries. The number of patients who
      eventually undergo surgery for these conditions might be relatively low; however,
      surgeons must be aware of them and consider them as differential diagnoses in
      refugees and migrants with acute or chronic abdominal symptoms.

PMID- 29344691
TI  - [A rare cause of acute pneumoperitoneum].

PMID- 29344692
TI  - The epidemiology of wrist fractures in older men: the Osteoporotic Fractures in
      Men (MrOS) study.
AB  - : There is limited wrist fracture information on men. Our goal was to calculate
      frequency and identify risk factors for wrist fracture in the Osteoporotic
      Fractures in Men (MrOS) study. We confirmed that fracture history and certain
      medications are predictors, and identified novel predictors including markers of
      kidney function and physical performance. INTRODUCTION: To calculate the
      incidence of wrist fractures and their risk factors in older community-dwelling
      men from the US Osteoporotic Fractures in Men (MrOS) study. METHODS: Using
      triannual postcards, we identified incident wrist fractures (centrally confirmed
      by radiology) in men aged >= 65. Potential risk factors included the following:
      demographics, lifestyle, bone mineral density (BMD), selected medications,
      biomarkers, and physical function and performance measures. Both baseline and
      time-varying models were adjusted for age, race/ethnicity, MrOS geographic
      location, and competing mortality risks. RESULTS: We observed 97 incident wrist
      fractures among 5875 men followed for an average of 10.8 years. The incidence of
      wrist fracture was 1.6 per 1000 person-years overall and ranged from 1.0 among
      men aged 65-69 to 2.4 among men age >= 80. Significant predictors included the
      following: fracture history after age 50 [hazard ratio (95% CI): 2.48 (1.65,
      3.73)], high serum phosphate [1.25 (1.02, 1.53)], use of selective serotonin
      receptor inhibitor (SSRI) [3.60 (1.96, 6.63), decreased right arm BMD [0.49
      (0.37, 0.65) per SD increase], and inability to perform the grip strength test
      [3.38 (1.24, 9.25)]. We did not find associations with factors commonly
      associated with wrist and other osteoporosis fractures like falls, diabetes,
      calcium and vitamin D intake, and alcohol intake. CONCLUSIONS: Among these older,
      community-dwelling men, we confirmed that fracture history is a strong predictor
      of wrist fractures in men. Medications such as SSRIs and corticosteroids also
      play a role in wrist fracture risk. We identified novel risk factors including
      kidney function and the inability to perform the grip strength test.

PMID- 29344694
TI  - Towards a better production of bacterial exopolysaccharides by controlling
      genetic as well as physico-chemical parameters.
AB  - Bacterial extracellular polymeric substances, which are basically bacterial
      metabolites, have currently become a subject of great concern of modern day
      microbiologists and biotechnologists. Among these metabolites, bacterial
      exopolysaccharides or EPS, in particular, have gained a significant importance.
      EPS are formed by the bacteria in their late exponential or stationary phase of
      growth under special situations for specific purposes. They take part in the
      formation of bacterial biofilms. There is a great diversity in the types of EPS.
      Strikingly enough, a same species of bacterium can produce different types of EPS
      under different situations. The importance of EPS is largely because of their
      different applications in various industries. Now that the bacterial EPS has got
      the potentiality to become an upcoming tool in various futuristic applications of
      human benefit, the focus currently develops towards how better they can be
      produced in the laboratory by promoting the favorable factors for their
      production. While studying with different EPS forming bacteria, both the
      intrinsic factors like genetic configuration of the bacteria and the extrinsic
      factors like culture conditions under the influence of different physico-chemical
      parameters in order to maximize the EPS production have been taken into
      consideration. Both the factors have proved their worth. Hence, towards a better
      outcome for EPS production, it is indicated that a genetic manipulation of the
      bacteria should be synchronized with a proper selection of its culture condition
      by controlling different physico-chemical parameters.

PMID- 29344693
TI  - Triplet-Based Codon Organization Optimizes the Impact of Synonymous Mutation on
      Nucleic Acid Molecular Dynamics.
AB  - Since the elucidation of the genetic code almost 50 years ago, many nonrandom
      aspects of its codon organization remain only partly resolved. Here, we
      investigate the recent hypothesis of 'dual-use' codons which proposes that in
      addition to allowing adjustment of codon optimization to tRNA abundance, the
      degeneracy in the triplet-based genetic code also multiplexes information
      regarding DNA's helical shape and protein-binding dynamics while avoiding
      interference with other protein-level characteristics determined by amino acid
      properties. How such structural optimization of the code within eukaryotic
      chromatin could have arisen from an RNA world is a mystery, but would imply some
      preadaptation in an RNA context. We analyzed synonymous (protein-silent) and
      nonsynonymous (protein-altering) mutational impacts on molecular dynamics in
      13823 identically degenerate alternative codon reorganizations, defined by codon
      transitions in 7680 GPU-accelerated molecular dynamic simulations of implicitly
      and explicitly solvated double-stranded aRNA and bDNA structures. When compared
      to all possible alternative codon assignments, the standard genetic code
      minimized the impact of synonymous mutations on the random atomic fluctuations
      and correlations of carbon backbone vector trajectories while facilitating the
      specific movements that contribute to DNA polymer flexibility. This trend was
      notably stronger in the context of RNA supporting the idea that dual-use codon
      optimization and informational multiplexing in DNA resulted from the
      preadaptation of the RNA duplex to resist changes to thermostability. The
      nonrandom and divergent molecular dynamics of synonymous mutations also imply
      that the triplet-based code may have resulted from adaptive functional expansion
      enabling a primordial doublet code to multiplex gene regulatory information via
      the shape and charge of the minor groove.

PMID- 29344695
TI  - Succession of microbial communities and changes of incremental oil in a post
      polymer flooded reservoir with nutrient stimulation.
AB  - Further exploitation of the residual oil underground in post-polymer flooded
      reservoirs is attractive and challengeable. In this study, indigenous microbial
      enhanced oil recovery (IMEOR) in a post-polymer flooded reservoir was performed.
      The succession of microbial communities was revealed by high-throughput
      sequencing of 16S rRNA genes and changes of incremental oil were analyzed. The
      results indicated that the abundances of reservoir microorganisms significantly
      increased, with alpha diversities decreased in the IMEOR process. With the
      intermittent nutrient injection, microbial communities showed a regular change
      and were alternately dominated by minority populations: Pseudomonas and
      Acinetobacter significantly increased when nutrients were injected; Thauera,
      Azovibrio, Arcobacter, Helicobacter, Desulfitobacterium, and Clostridium
      increased in the following water-flooding process. Accompanied by the stimulated
      populations, higher oil production was obtained. However, these populations did
      not contribute a persistent level of incremental oil in the reservoir. In
      summary, this study revealed the alternative succession of microbial communities
      and the changes of incremental oil in a post-polymer flooded reservoir with
      intermittent nutrient stimulation process.

PMID- 29344696
TI  - Reconstruction of the medial patellotibial ligament results in favorable clinical
      outcomes: a systematic review.
AB  - PURPOSE: The medial patellotibial ligament (MPTL), the medial patellofemoral
      ligament (MPFL), and the medial patellomeniscal ligament (MPML) support the
      stability of the patellofemoral joint. The purpose of this systematic review was
      to report the surgical techniques and clinical outcomes of the repair or
      reconstruction of the MPTL in isolation or concomitant with the MPFL and/or other
      procedures. METHODS: A systematic review of the literature was conducted.
      Inclusion criteria were articles in the English language that reported clinical
      outcomes of the reconstruction of the MPTL in isolation or in combination with
      the MPFL and/or other procedures. Included articles were then cross-referenced to
      find additional journal articles not found in the initial search. The
      methodological quality of the articles was determined using the Coleman
      Methodology Score. RESULTS: Nineteen articles were included detailing the
      clinical outcomes of 403 knees. The surgical procedures described included
      hamstrings tenodesis with or without other major procedures, medial transfer of
      the medial patellar tendon with or without other major procedures and the
      reconstruction of the MPTL in association with the MPFL. Overall, good and
      excellent outcomes were achieved in > 75% of cohorts in most studies and
      redislocations were < 10%, with or without the association of the MPFL. An
      exception was one study that reported a high failure rate of 82%. Results were
      consistent across different techniques. The median CMS for the articles was 66
      out of 100 (range 30-85). CONCLUSION: Across different techniques, the outcomes
      are good with low rates of recurrence, with one article reporting a high rate of
      recurrence. Quality of the articles is variable, from low to high. Randomized
      control trials are needed for a better understanding of the indications, surgical
      techniques, and clinical outcomes. This systematic review suggests that the
      reconstruction of the MPTL leads to favorable clinical outcomes and supports the
      role of the procedure as a valid surgical patellar stabilization procedure. LEVEL
      OF EVIDENCE: IV: systematic review of level I-IV studies.

PMID- 29344697
TI  - Could spouses of colorectal cancer patients possess higher risk of developing
      colorectal cancer?

PMID- 29344698
TI  - Concentrations of Cadmium, Copper, and Zinc in Macrobrachium rosenbergii (Giant
      Freshwater Prawn) from Natural Environment.
AB  - This study analyzed the levels of cadmium (Cd), copper (Cu), and zinc (Zn) by the
      flame atomic absorption spectrophotometer (FAAS), in the muscle tissues,
      exoskeletons, and gills from freshwater prawn (Macrobrachium rosenbergii) (n =
      20) harvested from natural habitat in Kerang River, Malaysia on 25th November
      2015. Significant increase of the metals level in muscle tissue and gill (r >
      0.70, p < 0.05) were observed with increase in length except for Cu in gills. No
      relationship was found between metals level in exoskeleton and length. The
      concentrations of Cd, Cu and Zn were significantly higher (p < 0.05) in males
      (muscle tissues and exoskeleton) except for Cd in exoskeleton. In gills, only Cu
      was significantly higher (p < 0.05) in female than male. All samples contained
      metals below the permissible limit for human consumption (i.e., Cd < 2.00 mg/kg;
      Cu < 30.00 mg/kg; Zn < 150 mg/kg). Annual metals monitoring in prawn and
      environmental samples is recommended to evaluate changes of metals
      bioaccumulation and cycling in the system, which is useful for resources
      management.

PMID- 29344699
TI  - Feasibility study of MR-guided transgluteal targeted in-bore biopsy for
      suspicious lesions of the prostate at 3 Tesla using a freehand approach.
AB  - OBJECTIVE: The aim of our study was (1) to establish an in-bore targeted biopsy
      of suspicious prostate lesions, avoiding bowel penetration using a transgluteal
      approach and (2) to assess operator setup, patient comfort and safety aspects in
      the clinical setting for freehand real-time MR-guidance established for
      percutaneous procedures in an open MR-scanner. MATERIAL AND METHODS: 30 patients
      with suspect prostate lesions were biopsied in a cylindrical 3T-MRI system using
      a transgluteal approach in freehand technique. One to three biopsies were sampled
      using continuous dynamic imaging. Size, location and visibility of the lesion,
      intervention time, needle artefact size, interventional complications and
      histopathological diagnosis were recorded. RESULTS: All biopsies were technically
      successful. Nineteen patients showed evidence of prostate carcinoma. Cancer
      detection rate was 50 % in patients with previously negative TRUS-biopsy. The
      average intervention time was 26 min including a learning curve as the time was
      13 min by the end of the study. No antibiotic prophylaxis was performed as none
      of the patients showed signs of infection. CONCLUSIONS: MR-guided targeted
      freehand biopsies of prostate lesions using a transgluteal approach are both
      technically feasible and time efficient in a standard closed-bore 3T-MR scanner
      as well as safe for the individual patient. KEY POINTS: * Open-bore freehand
      interventional principles were adapted to closed-bore systems. * Prostate MR
      guided freehand biopsies were feasible in a clinical setting. * A transgluteal
      approach provides a short and simplified work flow. * An inoculation of the
      prostate with bowel flora is avoided. * The intervention time is comparable to
      the stereotactic approach.

PMID- 29344700
TI  - Dual mobility hip arthroplasty provides better outcomes compared to
      hemiarthroplasty for displaced femoral neck fractures: a retrospective
      comparative clinical study.
AB  - PURPOSE: Total hip arthroplasty with a dual mobility cup (DMC) is a proposed
      alternative to the widely performed bipolar hemiarthroplasty (BHA) for treating
      displaced intracapsular femoral neck fractures (DFNF) in the elderly. However,
      the comparison between the two modalities has not been extensively conducted thus
      far. METHODS: A retrospective cohort study was conducted with DFNF patients aged
      over 65 years who were treated either by BHA or DMC. After propensity matching
      each group comprised 84 patients (168 patients in total) and was analyzed using
      peri-operative and post-operative parameters. RESULTS: Mean follow-up durations
      were 22.1 and 21.7 months in the BHA and DMC groups, respectively. The BHA group
      demonstrated significantly less intra-operative blood loss (p = 0.001) and a
      shorter length of operation (p < 0.001). However, there was no difference in one
      year mortality (p = 0.773). The Harris hip score (HHS) was significantly higher
      (p = 0.018) in the DMC group. The dislocation rate was not different between the
      two groups (p = 1.000). CONCLUSION: In DFNF patients aged over 65 years, short
      term observation showed DMC to be the preferred treatment over BHA with better
      clinical outcome, without disadvantages in mortality or dislocation rate. Further
      long-term investigations are recommended to strengthen these results.

PMID- 29344701
TI  - The fate of immunocompromised patients in the treatment of chronic periprosthetic
      joint infection: a single-centre experience.
AB  - PURPOSE: Immunocompromised patients with periprosthetic joint infection (PJI) are
      rare and currently there are no reliable guidelines according to which these
      infections can be successfully managed. The purpose of this study was to report
      the clinical course of different strategies for treatment of PJI in frail
      patients. METHODS: A retrospective analysis between 2004 and 2015 included 29
      immunocompromised patients (13 hips and 16 knees) with chronic PJI who underwent
      one-stage revision or debridement, antibiotics and implant retention (DAIR).
      Patients were stratified according to the Musculoskeletal Infection Society
      (MSIS) staging system and the clinical course included recurrence of infection
      and functional outcomes which were extracted from patients' charts. The average
      follow-up was 68 months (range, 26-149 months). RESULTS: Sixteen of the 29
      patients had recurrent infections. At last follow-up, 13 patients were on chronic
      suppressive antibiotic therapy, three patients died but not one death was
      considered to be related to the infection. A recurrent infection was observed in
      13 of the 24 medically compromised hosts (MSIS type B). Sixteen of the 24
      patients underwent one-stage revision; another eight of them underwent DAIR. The
      infection recurred in three of the five patients (60%) with the worst host grades
      (MSIS type C). One-stage revision was performed in one of the five patients and
      the remaining four patients received DAIR. CONCLUSION: Our results show that we
      should compromise our expectation and intemperate treatment for such a
      population. The goals of PJI treatment in these patients should take into account
      their preferences and may pay more attention to the concept of disease control
      rather than cure, especially for patients with severe comorbidities (MSIS C).
      LEVEL OF EVIDENCE: Therapeutic Level IV.

PMID- 29344702
TI  - [Mesenchymal abdominal tumors].

PMID- 29344704
TI  - [The role of PSMA PET-CT in patients with metastatic prostate cancer].
AB  - Prostate-specific membrane antigen (PSMA) positron emission tomography-computed
      tomography (PET-CT) imaging for the localization of prostate cancer is
      increasingly available in Germany. The advances and limitations in different
      disease stages are reviewed. As the clinical relevance of oligometastatic disease
      in primary cancer detected by PSMA PET-CT imaging is not yet completely
      understood, it should only be used in clinical trials. In recurrent prostate
      cancer after therapy with curative intent, PSMA PET-CT shows encouraging
      potential for the planning of salvage therapy. In metastatic castration-resistant
      prostate cancer evidence for its use is not available.

PMID- 29344705
TI  - [Which foot deformities should be radiologist be familiar with?]
AB  - Most deformities of the foot are visible at birth and can be diagnosed without
      imaging. They can be divided into congenital flexible, congenital structural and
      acquired foot deformities. The most common congenital flexible foot deformity in
      children is the metatarsus adductus, which usually requires no long-term therapy.
      Regarding congenital structural deformities, such as the clubfoot and talus
      verticalis, plaster therapy should be started during the first week of life, so
      that by the end of the first year of life and the beginning of the
      verticalization, a pain-free resilient foot with normal function is present.
      Imaging is usually only necessary if a relapse arises. Coalitio of the tarsal
      bones is often visible only in the course of growth through the development of a
      rigid flatfoot and always requires imaging to confirm the diagnosis. This article
      is intended to give the radiologist an overview of the most important deformities
      and to inform about their course and therapy.

PMID- 29344706
TI  - Long-term follow-up of 1217 consecutive short-stem total hip arthroplasty (THA):
      a retrospective single-center experience.
AB  - BACKGROUND: An arthroplasty registry in Germany has been recently established but
      long-term results for most short-stem innovations are missing. Short-stem hip
      arthroplasty is usually indicated in young active patients. Our indication was
      extended to older age groups, femoral neck fractures (FNF), and dysplasia. We
      evaluated all total hip arthroplasties (THAs) in this population with a collum
      femoris preserving stem (CFP) performed from 2003 to 2013. METHODS: A consecutive
      cohort of 1217 CFP THAs with a mean age of 68.7 years was followed
      retrospectively for a median of 4.8 years (patient follow-up interquartile range
      from 3.0 to 6.9 years). A questionnaire, which we used in two previous studies,
      was answered by 89.15% of patients and included information regarding complaints,
      grade of satisfaction, re-operations, and dislocation. Of the 1217 patients, 77
      had died. Survival of the stem and the cup was assessed using a competing risks
      approach according to an Aalen-Johanson estimator with revision for septic or
      aseptic loosening or death as a competing endpoint. RESULTS: Of the patients who
      answered the questionnaire, 92.5% had no complaints related to the procedures. In
      all 1217 patients, there were 43 revisions (4.2%) as follows: stem and cup
      revisions due to aseptic loosening of the stem (n = 10), infections (n = 6), pain
      (n = 4), or trauma (n = 3); cup revisions due to aseptic loosening (n = 3),
      dislocation (n = 5), and offset revisions (n = 12). Survivorship was 96% for the
      stem and 99% for the cup 9 years postoperatively. Statistical analysis confirmed
      a higher risk for revision in patients with a younger age (p = 0.033), male sex
      (p = 0.040), dysplasia (p = 0.032), and undersized or extra-large stems for stem
      revisions (p = 0.001) and female sex (p = 0.036) for cup revisions. FNF (p >
      0.20) and age >= 80 years (p = 0.114) had no higher risk for loosening of the
      stem. Our data is also compared with the current literature, especially with the
      available CFP studies. CONCLUSION: The survival rate of the CFP stem was as high
      as 96% after 9 years of followup which compares well-to-previously published long
      term survival rates. There is no higher risk for revision in patients 80 years
      old or older and in cases with femoral neck fractures. The CFP preserves also
      allowed using standard stems in the rare cases of revision.

PMID- 29344707
TI  - Effects of the establishment of a trauma center and a new protocol on patients
      with hemodynamically unstable pelvic fractures at a single institution in Korea.
AB  - PURPOSE: The aim of this study was to determine whether the outcomes of patients
      with hemodynamically unstable pelvic bone fractures changed after the
      introduction of a protocol including extraperitoneal pelvic packing (EPP) and the
      establishment of a trauma center. METHODS: We analyzed data of adult patients (>=
      18 years old) with hemodynamically unstable pelvic bone fractures who visited a
      single trauma center from February 2009 to October 2016. In July 2014, a new
      protocol for pelvic fractures was implemented, and a trauma center was
      established. Therefore, patient outcomes were compared by period (period I: pre
      protocol vs. period II: post-protocol). RESULTS: Seventy-nine patients with
      hemodynamically unstable pelvic bone fractures were recruited. The time to
      angiographic embolization after arrival at the emergency room decreased
      significantly in period II when compared to period I (182.9 vs. 268.9 min,
      respectively, p < 0.001). The time required to intervention, including EPP, also
      decreased, from 268.9 +/- 132.4 min in period I to 141.9 +/- 79.9 min in period
      II (p < 0.001). The overall mortality rate decreased from 47.2% in period I to
      23.3% in period II (p = 0.033), and mortality related to hemorrhagic shock in
      particular, was significantly lowered, from 27.8% in period I to 4.7% in period
      II (p = 0.009). CONCLUSIONS: The establishment of a trauma center and the
      implementation of a new protocol that included EPP were effective in the
      treatment of patients with hemodynamically unstable pelvic fractures.

PMID- 29344708
TI  - Treatment of combined traumatic brain injury and hemorrhagic shock with
      fractionated blood products versus fresh whole blood in a rat model.
AB  - INTRODUCTION: Treatment of combined traumatic brain injury and hemorrhagic shock,
      poses a particular challenge due to the possible conflicting consequences. While
      restoring diminished volume is the treatment goal for hypovolemia, maintaining
      adequate cerebral perfusion pressure and avoidance of secondary damage remains a
      treatment goal for the injured brain. Various treatment modalities have been
      proposed, but the optimal resuscitation fluid and goals have not yet been clearly
      defined. A growing body of evidence suggests that in hypovolemic shock,
      resuscitation with fresh whole blood (FWB) may be superior to component therapy
      without platelets (which are likely to be unavailable in the pre-hospital
      setting). Nevertheless, the effects of this approach have not been studied in the
      combined injury. Previously, in a rat model of combined injury we have found that
      mild resuscitation to MABP of 80 mmHg with FWB is superior to fluid resuscitation
      or aggressive resuscitation with FWB. In this study, we investigate the
      physiological and neurological outcomes in a rat model of combined traumatic
      brain injury (TBI) and hypovolemic shock, submitted to treatment with varying
      amounts of FWB, compared to similar resuscitation goals with fractionated blood
      products-red blood cells (RBCs) and plasma in a 1:1 ratio regimen. MATERIALS AND
      METHODS: 40 male Lewis rats were divided into control and treatment groups. TBI
      was inflicted by a free-falling rod on the exposed cranium. Hypovolemia was
      induced by controlled hemorrhage of 30% blood volume. Treatment groups were
      treated either with fresh whole blood or with RBC + plasma in a 1:1 ratio,
      achieving a resuscitation goal of a mean arterial blood pressure (MAP) of 80 mmHg
      at 15 min. MAP was assessed at 60 min, and neurological outcomes and mortality in
      the subsequent 24 h. RESULTS: At 60 min, hemodynamic parameters were improved
      compared to controls, but not significantly different between treatment groups.
      Survival rates at 48 h were 100% for both of the mildly resuscitated groups (MABP
      80 mmHg) with FWB and RBC + plasma. The best neurological outcomes were found in
      the group mildly resuscitated with FWB and were better when compared to
      resuscitation with RBC + plasma to the same MABP goal (FWB: Neurological Severity
      Score (NSS) 6 +/- 2, RBC + plasma: NSS 10 +/- 2, p = 0.02). CONCLUSIONS: In this
      study, we find that mild resuscitation with goals of restoring MAP to 80 mmHg
      (which is lower than baseline) with FWB, provided better hemodynamic stability
      and survival. However, the best neurological outcomes were found in the group
      resuscitated with FWB. Thus, we suggest that resuscitation with FWB is a feasible
      modality in the combined TBI + hypovolemic shock scenario, and may result in
      improved outcomes compared to platelet-free component blood products.

PMID- 29344709
TI  - Microbial Characterization of Methanogenic and Iron-reducing Consortium in
      Reactors with Polychlorinated Biphenyls.
AB  - Recent papers have confirmed current environmental pollution and the continuous
      release of polychlorinated biphenyls (PCBs) despite the prohibition of its
      manufacture worldwide. As the dehalogenating microorganisms are able to remove
      halogens from various analogous compounds, the characterization of PCB
      metabolisms can improve the degradation of similar compounds. Thus, this study
      extensively evaluated the microbial community developed in methanogenic and iron
      reducing reactors. The horizontal-flow anaerobic reactor (HAIB) with real waste
      of Aroclor (1 mL L-1) was fed with mineral medium, ethanol, and sodium formate.
      Bacteria belonging to Thermotogaceae (Thermotogae), Geobacteraceae, Chloroflexi,
      Proteobacteria, and Firmicutes (Clostridium) were identified in the HAIB reactor.
      Bacteria belonging to the Chloroflexi, Firmicutes, and Geobacteraceae are
      associated with the degradation of hydrocarbons and could be related to the
      Aroclor waste in this paper. Furthermore, 5.26 * 1012 cells gTVS-1 of iron
      reducing bacteria were quantified by the most probable number method in the HAIB
      reactor, suggesting that this group has an important role in aromatic
      degradation. Moreover, the evaluation of methanogenic and iron-reducing
      microorganisms in batch reactors with Aroclor 1260 was performed and the biomass
      growth was not affected by the addition of PCB. The methane production reached
      0.38 umol CH4 gTVS-1 and the iron reduction attained 90% in batch reactors.
      Through microbial analyses from HAIB and batch reactors, lower diversity was
      evidenced in the presence of PCB. This paper indicates the relevant role of iron
      reducing organisms and Chloroflexi, Geobacteraceae, and Firmicutes group in PCB
      metabolism.

PMID- 29344710
TI  - Radiation Doses to Operators in Hepatobiliary Interventional Procedures.
AB  - PURPOSE: The primary aim of this study is to provide a summary of operators'
      radiation doses during hepatobiliary fluoroscopic guided procedures. In addition,
      patient dose in these procedures was also documented. MATERIALS AND METHODS: A
      total of 283 transarterial chemoembolisation (TACE) and 302 biliary procedures,
      including 52 percutaneous transhepatic cholangiogram (PTC), 36 bilioplasty and
      214 biliary catheter changes (BCC) performed over 14 months, were included.
      Electronic personal dosimeters were used to measure operator radiation doses.
      Effective dose (E) was calculated using modified Niklason algorithm. Patient dose
      was measured as dose area product (DAP) and fluoroscopy time (FT). RESULTS: For
      TACE, E for radiologist ranged between 0 and 9.96 uSv, for radiographer 0-0.99
      uSv and for nurse 0-4.65 uSv. The patient DAP and FT ranged between 1.5 and 421.9
      Gy cm2 and 1.91-67.25 min. For PTC, E for the radiologist ranged between 0.33 and
      55.89 uSv, for radiographer 0-38.61 uSv and for nurse 0-3.18 uSv. Patient DAP and
      FT ranged between 1.7 and 218.4 Gy cm2 and 2.07-71.53 min. For bilioplasty, E
      ranged between 0.09 and 9.24 uSv for radiologist, 0-0.84 uSv for radiographer and
      0-1.38 uSv for nurse. The patients' DAP and FT ranged from 0.7 to 52.54 Gy cm2
      and 1.13-24.47 min. For BCC, E ranged from 0 to 12.78 uSv for radiologist, 0-8.43
      uSv for radiographer and 0-4.05 uSv for nurse. Patient DAP and FT ranged between
      0.12 and 117.3 Gy cm2 and 0.57-15.83 min. CONCLUSIONS: This study shows that
      doses to all operators performing hepatobiliary interventional procedures can be
      very low.

PMID- 29344711
TI  - Adult 'PICC' Device May be Used as a Tunnelled Central Venous Catheter in
      Children.
AB  - PURPOSE: Central venous access in children, in particular small children and
      infants, is challenging. We have developed a technique employing adult
      peripherally inserted central venous catheters (PICCs) as tunnelled central
      venous catheters (TCVCs) in children. The principal advantage of this novel
      technique is that the removal technique is less complex than that of conventional
      cuffed TCVCs. The catheter can be removed simply by being pulled out and does not
      require general anaesthesia. The purpose of this study is to determine the
      success, safety and utility of this technique and to identify the rate of late
      complications. We describe the 6-year experience in our unit. MATERIALS AND
      METHODS: Electronic and paper medical records were reviewed for consecutive
      paediatric patients who had a PICC device inserted as a TCVC over a 6-year period
      (September 2009 through July 2015). The following data were recorded-patient
      demographics, setting for PICC as TCVC insertion, use of ultrasound and
      fluoroscopy, PICC device type, early or late complications and date of and reason
      for removal. RESULTS: Twenty-one PICCs were inserted as TCVCs in 19 children, all
      aged less than 10 years. Mean patient age at the time of placement was 3.7 years.
      Average patient weight was 15.7 kg. All insertions were successful with no
      significant immediate complications recorded. The most common indication for
      insertion in our patient sample was pseudo-obstruction secondary to
      gastrointestinal dysmotility disorder (24%), with cystic fibrosis infective
      exacerbation being the second most frequent diagnosis (14%). Suspected catheter
      related infection led to early device removal in one case (4.8%). Inadvertent
      dislodgement occurred in one case (4.8%). Nineteen of the 21 devices (90.4%)
      lasted for the total intended duration of use. CONCLUSION: Using a PICC device as
      a TCVC in small children appears to be a safe technique, with an acceptable
      complication profile.

PMID- 29344714
TI  - Angiographic Anatomy and Relevance of 3 and 9 O'clock Arteries During
      Radioembolization.
AB  - PURPOSE: 3 and 9 o'clock arteries (3&9As) which supply the common hepatic duct
      connect hepatic with duodenal/pancreatic territories. The study purpose is to
      describe the angiographic anatomy of 3&9As and discuss their relevance when
      performing radioembolization (RE) of liver malignancies. MATERIALS AND METHODS:
      The anatomy of the 3&9As was systematically investigated by a retrospective
      analysis of angiograms, technetium Tc-99 m-macroaggregated albumin (MAA)
      scintigrams, yttrium-90 (Y90) Bremsstrahlung-SPECT/CT datasets, and clinical data
      of 153 patients who underwent RE between 2010 and 2013. RESULTS: Analysis of
      preprocedural angiograms identified 3&9As in 36 (24%) of the 153 patients.
      Following embolization of the gastroduodenal artery, 3&9As were seen in 53 cases
      (35%). The three most common origins of the 3&9As were the right hepatic artery
      (n = 14), the cystic artery (n = 11), and S5 and S6 segmental arteries (n = 5
      each). Extrahepatic Tc-99 m-MAA deposition in the territory of the 3&9As was
      significantly more frequent when 3&9As were detectable on preprocedural
      angiograms (28%visible vs. 11%not visible; p = 0.001) and especially when the
      3&9As were not embolized or bridged prior to RE (50%not occluded/bridged vs.
      19%occupied/bridged; p = 0.043). The presence of extrahepatic Y90 Bremsstrahlung
      after RE (n = 17) was attributable to microsphere diversion via the 3&9A
      territory in four patients and possible diversion via this territory in nine
      patients. Five of these 13 patients presented with epigastric pain, nausea, or
      vomiting (CTCAE severity grade <= 3) (p = 0.014). CONCLUSION: 3&9As are commonly
      detectable during evaluation angiography prior to RE, have a variable
      angioanatomic origin, and should be prophylactically occluded to prevent
      complications.

PMID- 29344713
TI  - Prognostic Factors in Overall Survival of Patients with Unresectable Intrahepatic
      Cholangiocarcinoma Treated by Means of Yttrium-90 Radioembolization: Results in
      Therapy-Naive Patients.
AB  - INTRODUCTION: To investigate prognostic factors in unresectable intrahepatic
      cholangiocarcinoma (ICC) therapy-naive patients after yttrium-90 (Y-90)
      radioembolization (RE) therapy. MATERIALS AND METHODS: Between 2005 and 2016, 21
      patients with ICC were treated with Y-90 RE only and their survival data were
      analyzed. Patients were stratified and response was assessed by the Response
      Evaluation Criteria in Solid Tumors (RECIST) criteria. RESULT: The overall median
      survival was 15 months. Survival was significantly (p = 0.009) prolonged in
      patients with tumor burden of <= 25% (n = 8, OS 37.5 months) versus those with a
      tumor burden of 25-50% (n = 13, OS 15 months). The other variables: tumor
      morphology (infiltrative vs. peripheral), tumor distribution (solitary vs.
      multifocal), lobes involved (unilobar vs. bilobar), FDG PET status (FDG avid vs.
      non-avid), RE treatment sessions (1 session vs. 2 sessions), metastases
      (metastasis vs. no metastasis) and RECIST criteria, had no significant impact on
      survival. CONCLUSION: Tumor burden represents a key prognostic factor of survival
      in therapy-naive patients with unresectable ICC treated with Y-90 RE therapy
      only.

PMID- 29344712
TI  - Usefulness of Hydrogel-Coated Coils in Embolization of Pulmonary Arteriovenous
      Malformations.
AB  - PURPOSE: To evaluate the usefulness of hydrogel-coated coils for preventing
      recanalization after coil embolization of pulmonary arteriovenous malformations
      (PAVMs). MATERIALS AND METHODS: Thirty-seven consecutive patients with 57
      untreated PAVMs underwent coil embolization with hydrogel-coated coils between
      January 2013 and Jun 2017. The mean age was 49 years (range 9-83 years), and
      there were seven male patients and 30 female patients. The median size of the
      feeding artery was 3.7 mm (range 1.5-6.1 mm), and the median size of the venous
      sac was 9.3 mm (range 2.6-36.6 mm). For all PAVM, embolization was attempted
      using 0.018-in. hydrogel-coated coils with or without other coils (0.0135-0.018
      in. bare platinum coils and fibered platinum coils). Technical success rate,
      recanalization rate, and complications were evaluated. Technical success was
      defined as completion of embolization using hydrogel-coated coils. Recanalization
      was evaluated with time-resolved magnetic resonance angiography and/or pulmonary
      angiography. RESULTS: In 56 of 57 PAVMs, embolization was successfully performed
      with hydrogel-coated coils. Therefore, the technical success rate was 98%
      (56/57). The number of PAVMs at risk was 56, 42, 18, and 12 at 0, 12, 24, and 36
      months, respectively. There was no recanalization with a mean follow-up period of
      19 months (range 2-47 months) in 56 PAVMs embolized with hydrogel-coated coils.
      There were no major complications. As a minor complication, local pain was
      observed in 8 of 43 sessions (19%) after embolization. CONCLUSIONS: Hydrogel
      coated coils may be useful for preventing recanalization after the embolization
      of PAVMs.

PMID- 29344715
TI  - A Case of Stent Fracture After Transjugular Intrahepatic Portosystemic Shunt.

PMID- 29344716
TI  - Safety and Effectiveness of Palliative Tunneled Peritoneal Drainage Catheters in
      the Management of Refractory Malignant and Non-malignant Ascites.
AB  - PURPOSE: To determine the safety and effectiveness of tunneled peritoneal
      catheters in the management of refractory malignant and non-malignant ascites.
      MATERIALS AND METHODS: An IRB-approved retrospective review was undertaken of
      patients who underwent ultrasound and fluoroscopy-guided tunneled peritoneal
      catheter placement for management of refractory malignant or non-malignant
      ascites between January 1, 2009, and March 14, 2014. RESULTS: A total of 137
      patients (76 M/61 F, mean age 62.9 years) underwent tunneled peritoneal catheter
      placement for refractory malignant (N = 119; 86.9%) or non-malignant (N = 18;
      13.1%) ascites. Technical success was 100% with no immediate complications.
      Nineteen patients (13.9%) experienced a total of 11 minor and 12 major
      complications. Nine patients developed a catheter-associated infection. The
      remaining complications included leakage at the dermatotomy site (N = 8),
      catheter dislodgement (N = 2), obstruction (N = 2), and groin pain (N = 2).
      Patients who developed a catheter-associated infection had a significantly longer
      catheter dwell time compared to those who did not develop an infection (median,
      96.5 vs. 20 days; p < 0.01). Nine patients (6.6%) were lost to follow-up. Of the
      remaining 128 patients, 125 died and the majority had a catheter in place (90.4%)
      at the time of death. There was one catheter-associated death (bacterial
      peritonitis; 0.8%). The median time from catheter placement to death was
      significantly shorter in patients with malignant versus non-malignant ascites
      (18.5 vs. 85 days; p < 0.0001). CONCLUSIONS: Tunneled peritoneal drainage
      catheters are effective and relatively safe in the management of malignant and
      non-malignant ascites. Longer catheter dwell time may be a risk factor for
      catheter-associated infection, particularly in patients with a longer anticipated
      survival in the palliative setting.

PMID- 29344717
TI  - Multiple Enlarged Aneurysms in Primary Racemose Hemangioma of the Bronchial
      Artery: Successful Prophylactic Transcatheter Arterial Embolization Using N-butyl
      2-cyanoacrylate and Coils.
AB  - An asymptomatic 48-year-old man presented with multiple aneurysms in a primary
      racemose hemangioma of the right bronchial artery. Bronchial arteriography
      revealed a tortuous artery with four fusiform aneurysms of varying sizes and
      aneurysmal dilatation with marked thrombus formation in the long segment of the
      distal portion. Because the tip of catheter could not pass beyond the aneurysmal
      dilatation, we performed balloon-occluded embolization using a mixture of N-butyl
      2-cyanoacrylate (NBCA) and iodized oil. For four other aneurysms, we performed
      embolization using a coil alone or with NBCA. After 6 months, right bronchial
      arteriography revealed no enhancement of the aneurysms. Despite the rarity of
      this procedure, embolization with NBCA is a good option for bronchial artery
      aneurysm embolization.

PMID- 29344718
TI  - Combination of baseline FDG PET/CT total metabolic tumour volume and gene
      expression profile have a robust predictive value in patients with diffuse large
      B-cell lymphoma.
AB  - PURPOSE: This study evaluated the predictive significance of total metabolic
      tumour volume (TMTV) measured on baseline FDG PET/CT and its value in addition to
      gene expression profiling using a new method of gene analysis (rapid reverse
      transcriptase multiplex ligation-dependent probe amplification assay, RT-MLPA) in
      patients with diffuse large B-cell lymphoma treated with R-CHOP or R-CHOP-like
      chemotherapies. METHODS: The analysis included 114 patients. TMTV was measured
      using a 41% SUVmax threshold and tumours were classified into GCB or ABC subtypes
      according to the RT-MLPA assay. RESULTS: The median follow-up was 40 months. the
      5-year progression-free survival (PFS) was 54% and the 5-year overall survival
      (OS) was 62%. The optimal TMTV cut-off value was 261 cm3. In 59 patients with a
      high TMTV the 5-year PFS and OS were 37% and 39%, respectively, in comparison
      with 72% and 83%, respectively, in 55 patients with a low TMTV (p = 0.0002 for
      PFS, p < 0.0001 for OS). ABC status was significantly associated with a worse
      prognosis. TMTV combined with molecular data identified three groups with very
      different outcomes: (1) patients with a low TMTV whatever their phenotype (n =
      55), (2) patients with a high TMTV and GCB phenotype (n = 33), and (3) patients
      with a high TMTV and ABC phenotype (n = 26). In the three groups, 5-year PFS
      rates were 72%, 51% and 17% (p < 0.0001), and 5-year OS rates were 83%, 55% and
      17% (p < 0.0001), respectively. In multivariate analysis, TMTV, ABC/GCB phenotype
      and International Prognostic Index were independent predictive factors for both
      PFS and OS (p < 0.05 for both). CONCLUSIONS: This integrated risk model could
      lead to more accurate selection of patients that would allow better
      individualization of therapy.

PMID- 29344719
TI  - Phosphorylation of vasodilator-stimulated phosphoprotein contributes to
      myocardial ischemic preconditioning.
AB  - Ischemic preconditioning (IP) is a well-known strategy to protect organs against
      cell death following ischemia. The previous work has shown that vasodilator
      stimulated phosphoprotein (VASP) is involved in cytoskeletal reorganization and
      that it holds significant importance for the extent of myocardial ischemia
      reperfusion injury. Yet, the role of VASP during myocardial IP is, to date, not
      known. We report here that VASP phosphorylation at serine157 and serine239 is
      induced during hypoxia in vitro and during IP in vivo. The preconditioning
      induced VASP phosphorylation inactivates the GP IIb/IIIa integrin receptor on
      platelets, which results in the reduced formation of organ compromising platelet
      neutrophil complexes. Experiments in chimeric mice confirmed the importance of
      VASP phosphorylation during myocardial IP. When studying this in VASP-/- animals
      and in an isolated heart model, we were able to confirm the important role of
      VASP on myocardial IP. In conclusion, we were able to show that IP-induced VASP
      phosphorylation in platelets is a protective mechanism against the deleterious
      effects of ischemia.

PMID- 29344720
TI  - Characteristics of pericytes in diethylstilbestrol (DES)-induced pituitary
      prolactinoma in rats.
AB  - Prolactinomas are the most common tumor of the human pituitary. They result in
      excessive prolactin secretion and important changes in the vasculature. Pericytes
      are perivascular cells associated with capillaries and have crucial roles in
      physiological and pathological neovascularization. We previously reported that
      pericytes produce type I and III collagens in the anterior pituitary of adult
      rats. In addition, pituitary pericytes contained well-developed cell organelles
      and actively synthesized collagens during early postnatal development. However,
      the characteristics of pericytes in pituitary tumors are unclear. In this study,
      we used diethylstilbestrol (DES)-treated rats as an animal model of prolactinoma.
      Using five common pericyte markers, more pericytes were observed in rats treated
      with DES for 3 months (prolactinoma) compared to the control. Transmission
      electron microscopy revealed that attached and semidetached pericytes exhibited
      active cell organelles. Moreover, we identified pericyte migration between
      capillaries. Although the fine structure of pituitary pericytes was active in
      prolactinoma, expressions of type I and III collagen mRNAs were greatly
      diminished. In sum, the characteristics and functions of pericytes were altered
      in pituitary tumors. This study is the first to clarify fine structural changes
      of pericytes in rat prolactinomas and improves our understanding of the function
      of pericytes under pathological conditions.

PMID- 29344721
TI  - Post-mortem MR angiography: quantitative investigation and intravascular
      retention of perfusates in ex situ porcine hearts.
AB  - As the implementation of minimally invasive imaging techniques in both forensic
      and pathological practice increases, research in this area focuses on addressing
      recognised diagnostic weaknesses of current approaches. Assessment of sudden
      cardiac death (SCD) can be considered one such area in which post-mortem imaging
      still shows diagnostic weaknesses. We hypothesise that magnetic resonance imaging
      (MRI) with an angiographic adjunct may improve the visualisation and
      interpretation of cardiac pathologies in a post-mortem setting. To systematically
      investigate this hypothesis, selected perfusates (paraffin oil, Gadovist(r);
      doped physiological solution and polyethylene glycol (PEG)) were injected into
      the left anterior descending (LAD) artery of ex situ porcine hearts to assess the
      visualisation of perfusates in MRI as well as their intravascular retention over
      12 h. Morphological images were acquired and quantitative T1 maps were generated
      from inversion recovery data. Visualisation of vascular structure and image
      quality were assessed using signal-to-noise and contrast-to-noise ratios.
      Intravascular retention was assessed both visually and statistically using a
      volume of interest (VOI) approach to analyse significant changes in signal
      intensity in and around the filled LAD artery, as well as changes in the
      longitudinal relaxation time (T1) in adjacent myocardium. In addition to
      presenting possible mechanisms explaining perfusate extravasation given the
      increased permeability of post-mortem vessels, the potential diagnostic
      consequences of this phenomenon and the importance of contrast stability and
      extended intravascular retention are discussed. In light of our findings and
      these considerations, paraffin oil emerged as the preferred perfusate for use in
      post-mortem MR angiography.

PMID- 29344722
TI  - Benefit of the addition of hormone therapy to neoadjuvant anthracycline-based
      chemotherapy for breast cancer: comparison of predicted and observed pCR.
AB  - INTRODUCTION: Neoadjuvant hormonal therapy is generally considered a valid option
      for hormone receptor positive breast cancer (BC) patients who are unfit for
      chemotherapy or surgery. AIMS: Whilst numerous studies analyzed efficacy of
      neoadjuvant chemotherapy (CT) or endocrine therapy (HT) alone in hormone receptor
      positive patients, there is a lack of research looking at the usefulness of a
      preoperative combinatorial approach of CT and HT in this patient subgroup.
      METHODS: Using a predictive model previously described in the literature,
      developed to analyze the probability of benefit from preoperative chemotherapy,
      we were able to compare pathological complete response (pCR) rates expected with
      the use of CT alone with the pCR rates reported in a population of 192 patients
      treated with the combination of tamoxifen plus anthracycline-based CT at Cremona
      Hospital between 2003 and 2006. RESULTS: Even with a relatively small patient
      population, this approach provided insightful information for the selection of
      hormone receptor positive BC patients most likely to benefit from the use of
      preoperative HT and CT in combination. Whilst no statistically significant
      benefit was obtained with the addition of tamoxifen to neoadjuvant chemotherapy
      in the entire population, or in any of the molecular stratification subgroups,
      the analysis of the calibration curve showed that a combinatorial approach may
      improve pCR in patients with luminal B tumors. More specific trials should be
      designed to confirm our initial results. CONCLUSION: To the best of our
      knowledge, this is the first report investigating the efficacy of the combination
      of CT and HT in the neoadjuvant treatment of hormone receptor positive BC.

PMID- 29344724
TI  - When the rhythm disappears and the mind keeps dancing: sustained effects of
      attentional entrainment.
AB  - Research has demonstrated that the human cognitive system allocates attention
      most efficiently to a stimulus that occurs in synchrony with an established
      rhythmic background. However, our environment is dynamic and constantly changing.
      What happens when rhythms to which our cognitive system adapted disappear? We
      addressed this question using a visual categorization task comprising emotional
      and neutral faces. The task was split into three blocks of which the first and
      the last were completed in silence. The second block was accompanied by an
      acoustic background rhythm that, for one group of participants, was synchronous
      with face presentations, and for another group was asynchronous. Irrespective of
      group, performance improved with background stimulation. Importantly, improved
      performance extended into the third silent block for the synchronous, but not for
      the asynchronous group. These data suggest that attentional entrainment resulting
      from rhythmic environmental regularities disintegrates only gradually after the
      regularities disappear.

PMID- 29344723
TI  - Structural associations between organelle membranes in nectary parenchyma cells.
AB  - MAIN CONCLUSION: The close association between membranes and organelles, and the
      intense chloroplast remodeling in parenchyma cells of extrafloral nectaries
      occurred only at the secretion time and suggest a relationship with the nectar
      secretion. Associations between membranes and organelles have been well
      documented in different tissues and cells of plants, but poorly explored in
      secretory cells. Here, we described the close physical juxtaposition between
      membranes and organelles, mainly with chloroplasts, in parenchyma cells of
      Citharexylum myrianthum (Verbenaeceae) extrafloral nectaries under transmission
      electron microscopy, using conventional and microwave fixation. At the time of
      nectar secretion, nectary parenchyma cells exhibit a multitude of different
      organelle and membrane associations as mitochondria-mitochondria, mitochondria
      endoplasmic reticulum, mitochondria-chloroplast, chloroplast-nuclear envelope,
      mitochondria-nuclear envelope, chloroplast-plasmalemma, chloroplast-chloroplast,
      chloroplast-tonoplast, chloroplast-peroxisome, and mitochondria-peroxisome. These
      associations were visualized as amorphous electron-dense material, a network of
      dense fibrillar material and/or dense bridges. Chloroplasts exhibited protrusions
      variable in shape and extension, which bring them closer to each other and to
      plasmalemma, tonoplast, and nuclear envelope. Parenchyma cells in the pre- and
      post-secretory stages did not exhibit any association or juxtaposition of
      membranes and organelles, and chloroplast protrusions were absent. Chloroplasts
      had peripheral reticulum that was more developed in the secretory stage. We
      propose that such subcellular phenomena during the time of nectar secretion
      optimize the movement of signaling molecules and the exchange of metabolites. Our
      results open new avenues on the potential mechanisms of organelle contact in
      parenchyma nectary cells, and reveal new attributes of the secretory cells on the
      subcellular level.

PMID- 29344725
TI  - Stimulating numbers: signatures of finger counting in numerosity processing.
AB  - Finger counting is one of the first steps in the development of mature number
      concepts. With a one-to-one correspondence of fingers to numbers in Western
      finger counting, fingers hold two numerical meanings: one is based on the number
      of fingers raised and the second is based on their ordinal position within the
      habitual finger counting sequence. This study investigated how these two
      numerical meanings of fingers are intertwined with numerical cognition in adults.
      Participants received tactile stimulation on their fingertips of one hand and
      named either the number of fingers stimulated (2, 3, or 4 fingers; Experiment 1)
      or the number of stimulations on one fingertip (2, 3, or 4 stimulations;
      Experiment 2). Responses were faster and more accurate when the set of stimulated
      fingers corresponded to finger counting habits (Experiment 1) and when the number
      of stimulations matched the ordinal position of the stimulated finger (Experiment
      2). These results show that tactile numerosity perception is affected by
      individual finger counting habits and that those habits give numerical meaning to
      single fingers.

PMID- 29344726
TI  - The safety and efficacy of elbasvir and grazoprevir in participants with
      hepatitis C virus genotype 1b infection.
AB  - BACKGROUND: Genotype 1b (GT1b) is the most common subtype of the hepatitis C
      virus (HCV). We present an integrated analysis of 1070 participants with HCV GT1b
      infection from 30 countries who received elbasvir/grazoprevir for 12 weeks.
      METHODS: This is a retrospective analysis of data from participants with chronic
      HCV GT1b infection enrolled in 11 phase II/III clinical trials. All participants
      received elbasvir 50 mg plus grazoprevir 100 mg once daily for 12 weeks. The
      primary end point of all studies was sustained virologic response 12 weeks after
      completion of therapy (SVR12, HCV RNA < 15 IU/ml). RESULTS: SVR12 was 97.2%
      (1040/1070). Of the 30 participants who failed to attain SVR12, 15 relapsed and
      15 had nonvirologic failure. Among participant subgroups, SVR12 was high in those
      with compensated cirrhosis (188/189, 99.5%), HIV co-infection (51/54, 94.4%), and
      baseline viral load > 800,000 IU/ml (705/728, 96.8%). Resistance-associated
      substitutions (RASs) at NS5A positions 28, 30, 31, or 93 were present in 21.6% of
      participants at baseline. SVR12 was 99.6% (820/823) in participants without
      baseline NS5A RASs and 94.7% (215/227) in those with baseline NS5A RASs. Serious
      adverse events occurred in 3.2% (34/1070) of participants, nine of which occurred
      after study medication was completed. CONCLUSIONS: Elbasvir/grazoprevir for 12
      weeks represents an effective treatment option for participants with HCV GT1b
      infection. SVR12 was high in all participant subgroups, including those with
      compensated cirrhosis, HIV co-infection, and high baseline viral load.
      CLINICALTRIALS. GOV IDENTIFIERS: The trials discussed in this paper were
      registered with Clinicaltrial.gov as the following: NCT02092350 (C-SURFER),
      NCT02105662 (C-EDGE Co-Infection), NCT02105467 (C-EDGE treatment-naive),
      NCT02105701 (C-EDGE treatment-experienced), NCT01717326 (C-WORTHy), NCT02251990
      (C-CORAL), NCT02105688 (C-EDGE COSTAR), NCT02252016 (C-EDGE IBLD), NCT02115321 (C
      SALT), NCT02203149 (Japan phase 2/3 study), NCT02358044 (C-EDGE Head-2-Head).

PMID- 29344728
TI  - [Cutaneous graft-versus-host disease].
AB  - BACKGROUND: Graft-versus-host disease (GvHD) is a complex multiorgan disease,
      which can occur as a complication following allogeneic stem cell transplantation.
      Involvement of the skin represents the most common appearance of GvHD. The role
      of the dermatologist is critical for diagnosis and initiation of treatment.
      OBJECTIVES: The aim of this article is to provide a comprehensive review of the
      cutaneous types of GvHD and to present the most recent data on diverse therapy
      options for its acute and chronic form allowing the clinician to establish a
      definite diagnosis and to initiate proper therapy. MATERIALS AND METHODS:
      Possible clinical appearances and recommended criteria to assist in making the
      right diagnosis are presented by means of expert recommendations. RESULTS AND
      CONCLUSION: GvHD is still a complex entity whose diagnosis is often associated
      with challenges due to its variable presentation. Proper diagnosis and subsequent
      therapy is paramount for the optimal clinical outcome.

PMID- 29344727
TI  - Work-related stress as a cardiovascular risk factor in police officers: a
      systematic review of evidence.
AB  - PURPOSE: Several studies suggest that work-related stress in police officers may
      be associated with an increased risk of cardiovascular diseases. A systematic
      review of studies is, however, still lacking. METHOD: According to PRISMA
      statement, a systematic search of PubMed, ISI Web of Science, Cinahl and
      PsychInfo electronic databases was undertaken. Studies published in English
      between 1/1/2000 and 31/12/2016 were included. A studies quality assessment was
      performed using the Newcastle Ottawa scale (NOS). RESULTS: The preliminary search
      retrieved 752 records. After selection, 16 studies (total population 17,698) were
      retrieved. The average quality of studies was low. Exposure to stress in cross
      sectional studies was inconstantly associated with hypertension, obesity,
      dyslipidaemia, and impaired glucose metabolism. In addition, there was a
      prevalence of positive studies showing an association between stress and
      cardiovascular disease morbidity. Studies of higher quality, such as longitudinal
      studies on large sample size, were more supportive of a significant positive
      association between stress and cardiovascular risk factors. Results were,
      however, often conflicting and inconsistent with regard to definitions and
      measurement of stress, features of individual study design, study conduct, and
      conclusions drawn. CONCLUSIONS: A sound precautionary principle would be to adopt
      worksite health promotion programs designed to implement stress management
      strategies in this category of workers.

PMID- 29344730
TI  - Skeletal dissemination in Paget's disease of the spine.
AB  - PURPOSE: Paget's disease of bone (PDB) is a common skeletal disorder that is
      associated with locally increased bone turnover, skeletal deformity and pain. We
      report a case of skeletal dissemination in PDB of the spine. METHODS: Case
      report. RESULTS: A 46-year-old former professional athlete suffered from
      disseminated PDB throughout the spine and hips after various surgical
      interventions including spondylodesis, bone grafting and bone morphogenetic
      protein (rhBMP-2) administration. Only intravenous zoledronic acid prevented the
      further progression of skeletal dissemination, which was expressed by a
      normalization of (bone-specific) alkaline phosphatase levels. The biopsy obtained
      from the lumbar spine confirmed the diagnosis of PDB in the absence of malignant
      transformation. CONCLUSIONS: We outline skeletal dissemination as a possibly
      surgery-related complication in a patient with PDB in the lumbar spine.
      Bisphosphonates remain the treatment of first choice in PDB and surgical
      interventions should be considered very carefully.

PMID- 29344729
TI  - Sodium bicarbonate supplementation improves severe-intensity intermittent
      exercise under moderate acute hypoxic conditions.
AB  - Acute moderate hypoxic exposure can substantially impair exercise performance,
      which occurs with a concurrent exacerbated rise in hydrogen cation (H+)
      production. The purpose of this study was therefore, to alleviate this acidic
      stress through sodium bicarbonate (NaHCO3) supplementation and determine the
      corresponding effects on severe-intensity intermittent exercise performance.
      Eleven recreationally active individuals participated in this randomised, double
      blind, crossover study performed under acute normobaric hypoxic conditions (FiO2%
      = 14.5%). Pre-experimental trials involved the determination of time to attain
      peak bicarbonate anion concentrations ([HCO3-]) following NaHCO3 ingestion. The
      intermittent exercise tests involved repeated 60-s work in their severe-intensity
      domain and 30-s recovery at 20 W to exhaustion. Participants ingested either 0.3
      g kg bm-1 of NaHCO3 or a matched placebo of 0.21 g kg bm-1 of sodium chloride
      prior to exercise. Exercise tolerance (+ 110.9 +/- 100.6 s; 95% CI 43.3-178 s; g
      = 1.0) and work performed in the severe-intensity domain (+ 5.8 +/- 6.6 kJ; 95%
      CI 1.3-9.9 kJ; g = 0.8) were enhanced with NaHCO3 supplementation. Furthermore, a
      larger post-exercise blood lactate concentration was reported in the experimental
      group (+ 4 +/- 2.4 mmol l-1; 95% CI 2.2-5.9; g = 1.8), while blood [HCO3-] and pH
      remained elevated in the NaHCO3 condition throughout experimentation. In
      conclusion, this study reported a positive effect of NaHCO3 under acute moderate
      hypoxic conditions during intermittent exercise and therefore, may offer an
      ergogenic strategy to mitigate hypoxic induced declines in exercise performance.

PMID- 29344731
TI  - The impact of surgeon volume on patient outcome in spine surgery: a systematic
      review.
AB  - PURPOSE: Recently, strategies aimed at optimizing provider factors have been
      proposed, including regionalization of surgeries to higher volume centers and
      adoption of volume standards. With limited literature promoting the
      regionalization of spine surgeries, we undertook a systematic review to
      investigate the impact of surgeon volume on outcomes in patients undergoing spine
      surgery. METHODS: We performed a systematic review examining the association
      between surgeon volume and spine surgery outcomes. To be included in the review,
      the study population had to include patients undergoing a primary or revision
      spinal procedure. These included anterior cervical discectomy and fusion (ACDF),
      anterior/posterior cervical fusion, laminectomy/decompression, anterior/posterior
      lumbar decompression with fusion, discectomy, and spinal deformity surgery (spine
      arthrodesis). RESULTS: Studies were variable in defining surgeon volume
      thresholds. Higher surgeon volume was associated with a significantly lower risk
      of postoperative complications, a lower length of stay (LOS), lower cost of
      hospital stay and a lower risk of readmissions and reoperations/revisions.
      CONCLUSIONS: Findings suggest a trend towards better outcomes for higher volume
      surgeons; however, further study needs to be carried out to define objective
      volume thresholds for individual spine surgeries for surgeons to use as a marker
      of proficiency.

PMID- 29344732
TI  - Recognition of the importance of geogenic sources in the content of metals in
      PM2.5 collected in the Mexico City Metropolitan Area.
AB  - The study of airborne metals in urban areas is relevant due to their toxic
      effects on human health and organisms. In this study, we analyzed metals
      including rare earth elements (REE) in particles smaller than 2.5 MUm (PM2.5),
      collected at five sites around the Mexico City Metropolitan Area (MCMA), during
      three periods in 2011: April (dry-warm season, DW), August (rainy season, R), and
      November (dry-cold season, DC). Principal component analysis allowed identifying
      factors related to geogenic sources and factors related to anthropogenic sources.
      The recognition of the high impact of geogenic sources in PM2.5 is in agreement
      with the REE distribution patterns, which show similar behavior as those shown by
      igneous rocks, confirming the influence of the regional geogenic material. Metals
      associated to geogenic sources showed higher concentration (p < 0.05) at NE of
      the MCMA and a significant correlation with prevalent winds. Geogenic metals show
      similar seasonal distribution, with the highest concentration during DW (p <
      0.05), suggesting a possible metal resuspension effect which affects more
      significantly at lower relative humidity (RH). The metals associated with
      anthropogenic sources are in agreement with the urban complexity of the area,
      showing homogenous distribution throughout MCMA (p > 0.05) and no similar
      seasonal pattern among them. These unexpected results exposed outstanding
      information regarding the identification of different geogenic sources as the
      main contributors of metals in the atmospheric environment in the MCMA and
      highlighted the importance of meteorology in the spatial and seasonal metal
      patterns.

PMID- 29344733
TI  - Linking intraspecific trait variability and spatial patterns of subtropical
      trees.
AB  - The importance of intraspecific trait variability (ITV) to the spatial
      distribution of individual species is unclear. We hypothesized that intraspecific
      trait dispersions underlying niche processes deviate more from null model
      expectations, by reducing their spread (range and variance), kurtosis, and
      standard deviation of near-neighbor distance, for species with aggregated than
      those with random distributions. The link between species' spatial distributions
      and ITV patterns was examined using an individual tree-based trait data set, in
      which specific leaf area, mean leaf area, leaf dry matter content, and diameter
      at breast height were measured for 18,773 stems of 45 species in a 4.84 ha mapped
      subtropical forest plot in China. The nearest-neighbor distance analysis showed
      that, of 45 species, 14 species were distributed in random and 31 species were
      distributed in aggregation, while no species was distributed in uniform in the
      plot. The dispersions of all studied traits in species with an aggregated
      distribution on average deviated more strongly from the null expectation than
      those in species with a random distribution and that the extent of deviation was
      negatively associated with the degree of spatial randomness across species. Our
      results indicate that niche processes are primarily responsible for the spatial
      structure of species with aggregated distributions, while stochastic processes
      drive those with random distributions. Our results highlight the fundamental role
      of ITV in shaping spatial patterns of co-existing species.

PMID- 29344734
TI  - The level and extent of upper airway obstruction affects the severity of
      laryngopharyngeal reflux.

PMID- 29344735
TI  - Hydrochemistry and water quality of Rewalsar Lake of Lesser Himalaya, Himachal
      Pradesh, India.
AB  - The present research is to study hydrochemistry and water quality of Rewalsar
      Lake during pre-monsoon, monsoon, and post-monsoon seasons. The Ca2+ and Na+ are
      observed as the dominant cations from pre- to post-monsoon season. On the other
      hand, HCO3- and Cl- are observed dominant anions during pre-monsoon and monsoon
      seasons, whereas HCO3- and SO42- during post-monsoon season. The comparison of
      alkaline earth metals with alkali metals and total cations (Tz+) has specified
      that the carbonate weathering is the dominant source of major ions in the water
      of lake.  The HCO3- is noticed to be mainly originated from carbonate/calcareous
      minerals during monsoon and post-monsoon, but through silicate minerals during
      pre-monsoon.  The SO42- in Rewalsar Lake is produced by the dissolution of
      calcite and dolomite etc. The alkali metals and Cl- in the lake can be attributed
      to the silicate weathering as well as halite dissolution and anthropogenic
      activities. Certain other parameters like NO3-, NH4+, F-, and Br- are mainly a
      result of anthropogenic activities. The alkaline earth metals are found to
      surpass over alkali metals, whereas weak acid (HCO3-) exceed to strong acid (SO42
      ). The Piper diagram has shown Ca2+-HCO3- type of water during all the seasons.
      The water quality index has indicated that the water quality of the lake is
      unsuitable for drinking from pre- to post-monsoon. Several parameters like
      salinity index, sodium adsorption ratio, sodium percent, residual sodium
      carbonate, magnesium hazard etc. have revealed the water of Rewalsar Lake as
      suitable for irrigation.

PMID- 29344736
TI  - Predictors of analgesic efficacy of neurolytic celiac plexus block in patients
      with unresectable pancreatic cancer: the importance of timing.
AB  - BACKGROUND: Neurolytic celiac plexus block (NCPB) is a safe and effective method
      for reducing abdominal cancer pain. However, the analgesic efficacy of NCPB is
      not always guaranteed. The aim of this retrospective study was to identify
      predictors for the analgesic efficacy of NCPB in patients with unresectable
      pancreatic cancer. METHODS: Patients with unresectable pancreatic cancer who
      underwent NCPB from 2006 to 2015 were enrolled. Good analgesia after NCPB was
      defined as >= 50% reduction in pain score at day 30. Patient demographics, cancer
      characteristics, and pain-related factors were evaluated using a logistic
      regression analysis to identify predictors for good analgesia after NCPB.
      Additionally, survival outcomes were compared between patients with poor and good
      analgesia after NCPB. RESULTS: A total of 112 patients satisfied the study
      protocol requirements. Forty-seven patients (41.9%) showed good analgesia after
      NCPB. Better performance status, lower serum CA 19-9 level, shorter pain
      duration, and lower opioid dose were observed in patients with good analgesia
      after NCPB. Good performance status (ECOG performance status 1 vs. 2 or 3, OR =
      2.737, 95% CI = 1.149 to 6.518, P = 0.023) and low daily opioid use (< 150 vs. >=
      150 mg, OR = 2.813, 95% CI = 1.159 to 6.831, P = 0.022) before NCPB were
      independent predictors of good analgesia after NCPB. The median survival was
      significantly lower for patients with poor analgesia after NCPB (68 vs. 150 days,
      P < 0.001). CONCLUSION: NCPB should be offered early to selected patients to
      improve its analgesic efficacy in advance of deterioration from disease and pain
      in this population.

PMID- 29344737
TI  - The 125th anniversary of the His bundle discovery.
AB  - In 1893, Wilhelm His Jr. was the first to describe the AV (atrioventricular)
      bundle of the vertebrate heart, which now bears his name. Moreover, prior to the
      turn of the century, W. His Jr. had proved the function of the AV bundle by
      transection experiments in animals, and had interpreted Adams Stokes disease as
      heart block due to pathological changes within the bundle. In this way, he was
      ahead of his time. While clinical interest was limited to the bundle as the
      location of an AV block in the first half of the 125 years, it has gained
      attractiveness since then as a target of diagnostic and therapeutic procedures.
      The introduction of His bundle electrography relaunched the interest in cardiac
      arrhythmias. Once the AV bundle could be localized clinically, its ablation, and
      in recent times its permanent stimulation, became options in the therapy of well
      defined arrhythmia and conduction problems.

PMID- 29344738
TI  - Genetic and functional analysis of the RYR1 mutation p.Thr84Met revealed a
      susceptibility to malignant hyperthermia.
AB  - PURPOSE: The aim of this study was to analyze the genetic and functional role of
      a novel RYR1 variant c.251 C > T (p.Thr84Met) identified in a patient with muscle
      weakness demonstrating MH susceptibility. METHODS: DNA testing of family members
      was conducted for assessment of pathogenicity of the genetic variant. For
      functional analysis, Ca2+ measurement using patient-derived myotubes and
      p.Thr84Met RYR1-transfected human embryonic kidney (HEK)-293 cells was performed
      to evaluate reactivity to RYR1 activators. The half-maximal effective
      concentration (EC50) values of two RYR1 activators, caffeine and 4-chloro-m
      cresol (4CmC), were calculated from the acquired dose-response curves. The EC50
      was compared between two groups: for myotubes, the control group and the patient,
      and for HEK-293 cells, WT and p.Thr84Met. RESULTS: Dose-response curves for
      caffeine and 4CmC were shifted to the left in both myotubes and HEK-293 cells
      compared to controls. The 50% effective concentration values for caffeine and
      4CmC were significantly lower in both myotubes and HEK-293 cells compared to
      controls (P < 0.001 for all comparisons). CONCLUSIONS: Our results of functional
      testing indicated RYR1 hypersensitivity to caffeine and 4CmC. We conclude that
      the genetic variant was associated with MH susceptibility.

PMID- 29344739
TI  - What We Have Learned from the Recent Meta-analyses on Diagnostic Methods for
      Atherosclerotic Plaque Regression.
AB  - PURPOSE OF REVIEW: Atherosclerosis has major morbidity and mortality implications
      globally. While it has often been considered an irreversible degenerative
      process, recent evidence provides compelling proof that atherosclerosis can be
      reversed. Plaque regression is however difficult to appraise and quantify, with
      competing diagnostic methods available. Given the potential of evidence synthesis
      to provide clinical guidance, we aimed to review recent meta-analyses on
      diagnostic methods for atherosclerotic plaque regression. RECENT FINDINGS: We
      identified 8 meta-analyses published between 2015 and 2017, including 79 studies
      and 14,442 patients, followed for a median of 12 months. They reported on
      atherosclerotic plaque regression appraised with carotid duplex ultrasound,
      coronary computed tomography, carotid magnetic resonance, coronary intravascular
      ultrasound, and coronary optical coherence tomography. Overall, all meta-analyses
      showed significant atherosclerotic plaque regression with lipid-lowering therapy,
      with the most notable effects on echogenicity, lipid-rich necrotic core volume,
      wall/plaque volume, dense calcium volume, and fibrous cap thickness. Significant
      interactions were found with concomitant changes in low density lipoprotein
      cholesterol, high density lipoprotein cholesterol, and C-reactive protein levels,
      and with ethnicity. Atherosclerotic plaque regression and conversion to a stable
      phenotype is possible with intensive medical therapy and can be demonstrated in
      patients using a variety of non-invasive and invasive imaging modalities.

PMID- 29344740
TI  - Trends in Awareness and Use of HIV PrEP Among Gay, Bisexual, and Other Men who
      have Sex with Men in Vancouver, Canada 2012-2016.
AB  - Gay, bisexual, and other men who have sex with men (gbMSM) are at the highest
      risk for HIV infection in British Columbia (BC). Pre-exposure prophylaxis (PrEP)
      has been recently licensed but is currently not publicly funded in BC. Using
      respondent-driven sampling, we recruited a cohort of gbMSM to complete a computer
      assisted self-interview with follow-up every 6 months. Stratified by HIV status,
      we examined trends in awareness of PrEP from 11/2012 to 02/2016 and factors
      associated with PrEP awareness. 732 participants responded to the PrEP awareness
      question. Awareness of PrEP among HIV-negative men increased from 18 to 80% (p <
      0.0001 for trend); among HIV-positive men, awareness increased from 36 to 77% (p
      < 0.0001). PrEP awareness was associated with factors related to HIV risk
      including sero-adaptive strategies and sexual sensation seeking. Eight HIV
      negative men reported using PrEP. Low PrEP uptake highlights that PrEP access
      should be expanded for at-risk gbMSM in BC.

PMID- 29344741
TI  - Assessment of potential risk factors for breast cancer in a population in
      Southern Brazil.
AB  - PURPOSE: The aim of this study is to assess potential risk factors for breast
      cancer in a population in Southern Brazil and build a multivariate logistic model
      using these factors for breast cancer risk prediction. METHODS: A total of 4242
      women between 40 and 69 years of age without a history of breast cancer were
      selected at primary healthcare facilities in Porto Alegre and submitted to
      mammographic screening. They were evaluated for potential risk factors. RESULTS:
      In all, 73 participants among the 4242 women had a breast cancer diagnosis during
      the follow-up of the project (10 years). The multivariate analysis considering
      all the patients aged 40-69 years showed that older age (OR 1.08, 95% CI 1.04
      1.12), higher height (OR 1.04, 95% CI 1.01-1.09), and history of previous breast
      biopsy (OR 2.66, 95% CI 1.38-5.13) were associated with the development of breast
      cancer. Conversely, the number of pregnancies (OR 0.87, 95% CI 0.78-0.98) and use
      of hormone replacement therapy (OR 0.39, 95% CI 0.20-0.75) were considered a
      protective factor. Additionally, we performed an analysis separating the
      participants into groups of 40-49 and 50-69 years old, since a risk factor could
      have a specific behavior in these age groups. No additional risk factors were
      identified within these age brackets, and some factors lost statistical
      significance. CONCLUSION: The risk prediction model indicates that the following
      variables should be assessed in this specific population: age, height, having had
      previous breast biopsies, number of pregnancies, and use of hormone replacement
      therapy. These findings may help to better understand the causal model of breast
      cancer in Southern Brazil.

PMID- 29344742
TI  - Increased Curie Temperature Induced by Orbital Ordering in
      La0.67Sr0.33MnO3/BaTiO3 Superlattices.
AB  - Recent theoretical studies indicated that the Curie temperature of perovskite
      manganite thin films can be increased by more than an order of magnitude by
      applying appropriate interfacial strain to control orbital ordering. In this
      work, we demonstrate that the regular intercalation of BaTiO3 layers between
      La0.67Sr0.33MnO3 layers effectively enhances ferromagnetic order and increases
      the Curie temperature of La0.67Sr0.33MnO3/BaTiO3 superlattices. The preferential
      orbital occupancy of eg(x 2 -y 2 ) in La0.67Sr0.33MnO3 layers induced by the
      tensile strain of BaTiO3 layers is identified by X-ray linear dichroism
      measurements. Our results reveal that controlling orbital ordering can
      effectively improve the Curie temperature of La0.67Sr0.33MnO3 films and that in
      plane orbital occupancy is beneficial to the double exchange ferromagnetic
      coupling of thin-film samples. These findings create new opportunities for the
      design and control of magnetism in artificial structures and pave the way to a
      variety of novel magnetoelectronic applications that operate far above room
      temperature.

PMID- 29344743
TI  - Response to different furosemide doses predicts AKI progression in ICU patients
      with elevated plasma NGAL levels.
AB  - BACKGROUND: Furosemide responsiveness (FR) is determined by urine output after
      furosemide administration and has recently been evaluated as a furosemide stress
      test (FST) for predicting severe acute kidney injury (AKI) progression. Although
      a standardized furosemide dose is required for FST, variable dosing is typically
      employed based on illness severity, including renal dysfunction in the clinical
      setting. This study aimed to evaluate whether FR with different furosemide doses
      can predict AKI progression. We further evaluated the combination of an AKI
      biomarker, plasma neutrophil gelatinase-associated lipocalin (NGAL), and FR for
      predicting AKI progression. RESULTS: We retrospectively analyzed 95 patients who
      were treated with bolus furosemide in our medical-surgical intensive care unit.
      Patients who had already developed AKI stage 3 were excluded. A total of 18
      patients developed AKI stage 3 within 1 week. Receiver operating curve analysis
      revealed that the area under the curve (AUC) values of FR and plasma NGAL were
      0.87 (0.73-0.94) and 0.80 (0.67-0.88) for AKI progression, respectively. When
      plasma NGAL level was < 142 ng/mL, only one patient developed stage 3 AKI,
      indicating that plasma NGAL measurements were sufficient to predict AKI
      progression. We further evaluated the performance of FR in 51 patients with
      plasma NGAL levels > 142 ng/mL. FR was associated with AUC of 0.84 (0.67-0.94)
      for AKI progression in this population with high NGAL levels. CONCLUSIONS:
      Although different variable doses of furosemide were administered, FR revealed
      favorable efficacy for predicting AKI progression even in patients with high
      plasma NGAL levels. This suggests that a combination of FR and biomarkers can
      stratify the risk of AKI progression in a clinical setting.

PMID- 29344744
TI  - Interleukin-1 receptor antagonist inhibits angiogenesis in gastric cancer.
AB  - BACKGROUND: Interleukin-1 alpha (IL-1alpha) plays an important role in
      tumorigenesis and angiogenesis of gastric cancer. The interleukin-1 receptor
      antagonist (IL-1RA) inhibits IL-1 selectively and specifically through IL-1R type
      I (IL-1RI). However, the underlying mechanism by which IL-1RA modulates the
      interactions of tumor cells and their micro-environment is poorly understood. We
      have evaluated the role of IL-1RA in the metastatic process as well as the mutual
      or reciprocal actions between gastric cancer cells and stromal cells. MATERIALS
      AND METHODS: The expressions of IL-1alpha, vascular endothelial growth factor
      (VEGF), and IL-1RI mRNA were determined by reverse transcriptase-PCR. The
      regulatory effect of IL-1RA on the secretion of VEGF in human gastric cancer
      cells and human umbilical vein endothelial cells (HUVECs) was detected by enzyme
      linked immunosorbent assay. The effect of IL-1RA on metastatic potential was
      evaluated using proliferation, invasion, and angiogenesis assays, respectively,
      including in vitro co-culture system models consisting of tumor cells and stromal
      cells that were used to detect invasion and angiogenesis. RESULTS: Interleukin
      1alpha mRNA was detected in the higher liver metastatic gastric cell line MKN45.
      IL-1alpha protein was expressed in MKN45 cells and in HUVECs. VEGF mRNA and
      protein were detected in the three gastric cancer cell lines (MKN4, NUGC-4, and
      AGS). Levels of VEGF secreted by gastric cancer cells and HUVECs appeared to be
      reduced through the action of IL-1RA via IL-1RI in a dose-dependent manner (P <
      0.01). IL-1RA significantly inhibited the proliferation and migration of HUVECs
      (P < 0.01) and tube formation by HUVECs (P < 0.01), both in a dose-dependent
      manner. Compared with HUVECs grown without cancer cells (control) or with NUGC-4
      cells, tube formation by HUVECs was significantly enhanced by co-culture with
      MKN45 cells (P < 0.01). The enhanced tube formation in the presence of MKN45
      cells was inhibited by the addition of IL-1RA (P < 0.01). CONCLUSIONS: The IL-1RA
      downregulated the metastatic potential of gastric cancer through blockage of the
      IL-1alpha/VEGF signaling pathways. IL-1RA has the potential to play a role in the
      treatment of gastric cancer.

PMID- 29344745
TI  - Wet milling of large quantities of human excision adipose tissue for the
      isolation of stromal vascular fraction cells.
AB  - The isolation of stromal vascular fraction (SVF) cells from excised human adipose
      tissue, for clinical or research purposes, implies the tedious and time consuming
      process of manual mincing prior to enzymatic digestion. Since no efficient
      alternative technique to this current standard procedure has been proposed so
      far, the aim of this study was to test a milling procedure, using two simple,
      inexpensive and commercially available manual meat grinders, to process large
      amounts of adipose tissue. The procedure was assessed on adipose tissue
      resections from seven human donors and compared to manual mincing with scalpels.
      The processed adipose tissues were digested and the resulting SVF cells compared
      in terms of number, clonogenicity and differentiation capacity. After 10 min of
      processing, either device tested yielded on average sixfold more processed
      material for subsequent cell isolation than manual mincing. The isolation yield
      of SVF cells (isolated cells per ml of adipose tissue), their viability,
      phenotype, clonogenicity and osteogenic/adipogenic differentiation capacity,
      tested by production of mineralized matrix and lipid vacuoles, respectively, were
      comparable. This new method is practical and inexpensive and represents an
      efficient alternative to the current standard for large scale adipose tissue
      resection processing. A device based on the milling principle could be embedded
      within a streamlined system for isolation and clinical use of SVF cells from
      adipose tissue excision.

PMID- 29344746
TI  - Desvenlafaxine-Induced Interstitial Pneumonitis: A Case Report.
AB  - A 52-year-old man developed interstitial pneumonitis during treatment with
      desvenlafaxine for major depressive disorder. The man received desvenlafaxine at
      50 mg for symptoms of depression 4 years earlier. Six months after a dose
      increase to 100 mg, he developed bronchitic symptoms with mild, persistent
      dyspnea. Investigations revealed a restrictive pattern on pulmonary function
      testing, bilateral upper lobe reticular opacities with traction bronchiectasis on
      radiology imaging, and end-stage interstitial fibrosis with honeycomb changes
      consistent with chronic hypersensitivity pneumonitis on open lung biopsy. He was
      diagnosed with drug-induced interstitial pneumonitis. Desvenlafaxine was
      discontinued and the patient received prednisone and mycophenolate mofetil. The
      patient had subsequent stability in the progression of his pulmonary disease
      after 1 month. After 1 year of drug discontinuation and treatment, his disease
      process remained, but without major progression. A Naranjo assessment score of 4
      was obtained, indicating a possible relationship between the patient's adverse
      drug reaction and his use of the suspect drug.

PMID- 29344747
TI  - Healthcare-based on Cloud Electrocardiogram System: A Medical Center Experience
      in Middle Taiwan.
AB  - Electrocardiogram (ECG) as one of the best methods to measure irregular
      heartbeats is a dispensable method for doctor to diagnose Acute Myocardial
      Infarction (AMI) patients. Most medical centers in Taiwan implement the reduction
      of Door to Balloon (D2B) time, which is defined as the time interval starting
      when an Acute-Myocardial-Infarction patient arrives at the Emergency Department,
      and ending when a catheter guide wire crosses the culprit lesion as the acute
      myocardial-infarction treatment on the patient in the cardiac catheterization
      room. Generally, when a patient with acute-chest pain is sent into a hospital
      (always to Emergency Department), the hospital will collect his/her ECG which
      needs to be evaluated by a cardiologist to ensure that the patient really has
      Acute Myocardial Infarction. Then the medical workers deliver the patient to the
      cardiac catheterization room to operate balloon angioplasty. In previous years,
      the cardiologist must utilize a PC to connect to the Intranet of the hospital and
      employ a special PACS (Picture Archiving and Communication System) image browser
      before he/she can check the patient's ECG. But this will prolong the D2B time
      since the doctor may stay outdoors and he/she needs some time to find a PC and
      network. Of course, if the PC has not installed the PACS image browser, the
      doctor has to download and install it. Consequently, the D2B time should be
      worsened, thus possibly impacting the patient's life. Therefore, in this paper,
      we introduce a Cloud-based Electrocardiogram System, with which cardiologists can
      directly utilize their smart phones to browse the patient's ECG so as to shorten
      the D2B time. This system has been online in a medical center in middle Taiwan
      for more than one year. The shortened D2B time is longer than 10 min, i.e.,
      receiving fine results.

PMID- 29344748
TI  - Lead sorption characteristics of various chicken bone part-derived chars.
AB  - Recycling food waste for beneficial use is becoming increasingly important in
      resource-limited economy. In this study, waste chicken bones of different parts
      from restaurant industry were pyrolyzed at 600  degrees C and evaluated for char
      physicochemical properties and Pb sorption characteristics. Lead adsorption
      isotherms by different chicken bone chars were carried out with initial Pb
      concentration range of 1-1000 mg L-1 at pH 5. The Pb adsorption data were better
      described by the Langmuir model (R2 = 0.9289-0.9937; ARE = 22.7-29.3%) than the
      Freundlich model (R2 = 0.8684-0.9544; ARE = 35.4-72.0%). Among the chars derived
      from different chicken bone parts, the tibia bone char exhibited the highest
      maximum Pb adsorption capacity of 263 mg g-1 followed by the pelvis (222 mg g-1),
      ribs (208 mg g-1), clavicle (179 mg g-1), vertebrae (159 mg g-1), and humerus
      (135 mg g-1). The Pb adsorption capacities were significantly and positively
      correlated with the surface area, phosphate release amount, and total phosphorus
      content of chicken bone chars (r >= 0.9711). On the other hand, approximately 75
      88% of the adsorbed Pb on the chicken bone chars was desorbable with 0.1 M HCl,
      indicating their recyclability for reuse. Results demonstrated that chicken bone
      char could be used as an effective adsorbent for Pb removal in wastewater.

PMID- 29344749
TI  - Diagnosis of sleep apnea in patients with stable chronic heart failure using a
      portable sleep test diagnostic device.
AB  - PURPOSE: ApneaLink is a portable device for the screening of sleep apnea, a
      prevalent and underdiagnosed comorbidity in heart failure patients. A prospective
      cross-sectional study in patients with chronic heart failure was carried out to
      assess the sensitivity and specificity of apnea-hypopnea index (AHI) measurements
      using ApneaLink against the standard polysomnography test. METHODS: Adult
      patients with a prior hospitalization in an acute heart failure hospital unit
      were recruited for the study. All participants were tested for sleep apnea using
      ApneaLink and polysomnography simultaneously during an overnight stay at a sleep
      laboratory. Global sleep apnea was evaluated according to the AHI, which was
      analyzed and compared. Subpopulation comparison based on ejection fraction was
      not realized due to population size. RESULTS: Thirty-five patients with stable
      chronic heart failure completed the study (mean age 70.9 +/- 10.5 years and body
      mass index 30.0 +/- 4.7 kg/m2). Two patients were excluded due to insufficient
      study duration. ApneaLink had a sensitivity greater than 80% for all AHI
      measurements, and a specificity greater than 80% for all AHI measurements, except
      for AHI >= 5 events/h (61.5%). The results showed higher sensitivities and
      specificities at AHI values of >= 10 events/h (sensitivity 81.3% and specificity
      84.2%) and >= 15 events/h (sensitivity 83.3% and specificity 91.3%). Correlation
      analysis showed that AHI measurements using ApneaLink and polysomnography had a
      strong and significant correlation (r = 0.794; P < 0.001). CONCLUSIONS: Our
      results suggest that ApneaLink could be used in clinical practice to identify
      heart failure patients with high (AHI >= 15 events/h) and low (AHI < 5 events/h)
      probability of having sleep apnea, sparing the need for a diagnostic
      polysomnography and thus potentially impacting prognosis by providing a more cost
      effective and timely diagnosis of this non-cardiac comorbidity.

PMID- 29344751
TI  - Associations Between Early Intervention Home Visits, Family Relationships and
      Competence for Mothers of Children with Developmental Disabilities.
AB  - Objectives To examine the association between intensity of home visits in early
      intervention (EI), perceived helpfulness of home visits in EI, and positive
      family relationships as predictors of maternal competence at age 3, as well as
      moderating effects of predictors, controlling for child characteristics, family
      demographics, and negative life events. Methods Data were drawn from the Early
      Intervention Collaborative Study (EICS), a 24-year longitudinal investigation of
      approximately 190 families of children with developmental disabilities who
      participated in EI programs in Massachusetts and New Hampshire. The primary
      analytic strategy was multivariable regression modeling. Each independent
      predictor was tested individually and then all together to build the final model.
      Interactions between independent predictors were also examined. Results After
      controlling for child and family characteristics and negative life events, the
      intensity of home visits was not significantly associated with maternal
      competence at age 3. However, the helpfulness of home visits (beta = 2.94, S.E. =
      1.12, p < .01) and positive family relationships (beta = 5.11, S.E. = 1.08, p <
      .001) were associated with higher maternal competence when the child was 3 years
      old. Conclusions for Practice Recommendations for programs and policy include
      collecting life course data on families, particularly on their family
      relationships and experiences in EI and home visiting, assessing family
      relationships at the beginning of EI using a strengths-based perspective, and
      closely monitoring the quality of services.

PMID- 29344750
TI  - Physical Activity and Consumption Patterns of Reproductive-Aged Women by BMI
      Category.
AB  - Objectives Obesity before and during pregnancy is associated with adverse effects
      for mother and child, but little is known about physical activity and consumption
      patterns among reproductive-aged women. The goal of this study is to identify
      behaviors of nonpregnant reproductive-aged women associated with normal weight,
      overweight, and obesity. Methods Data from the nationally representative National
      Eating Trends survey (2003-2011) were analyzed, comparing number of days of
      exercise in a 1-week period and consumption of fruits/vegetables, sugar sweetened
      beverages (SSB), and concentrated sweets by BMI. Behaviors were compared using
      analysis of variance and Chi square test across groups. Ordinal logistic
      regression was used to compare behaviors across groups controlling for
      demographic factors. Multivariable Poisson regression was used to identify
      demographic factors associated with behaviors among obese women. Results Among
      5941 18-45-year-old women, exercise and fruit/vegetable consumption were
      associated with healthy weight controlling for demographic factors. Reporting any
      exercise or fruit/vegetable consumption was associated with decreased odds of
      overweight or obesity (aOR 0.73, 95% CI 0.64-0.83 and aOR 0.74, 95% CI 0.58-0.95,
      respectively). Consuming SSBs was associated with increasing BMI category while
      consuming concentrated sweets was unexpectedly associated with normal weight.
      Among obese women, being on any diet was associated with increased exercise
      frequency and fruit/vegetable consumption and decreased SSB consumption.
      Conclusions for Practice Physical activity and consumption behaviors are
      associated with weight among reproductive-aged women in ways similar to those in
      the general population. Promoting exercise and fruit/vegetable consumption has
      the potential to reduce obesity.

PMID- 29344752
TI  - Transforming Dermatologic Imaging for the Digital Era: Metadata and Standards.
AB  - Imaging is increasingly being used in dermatology for documentation, diagnosis,
      and management of cutaneous disease. The lack of standards for dermatologic
      imaging is an impediment to clinical uptake. Standardization can occur in image
      acquisition, terminology, interoperability, and metadata. This paper presents the
      International Skin Imaging Collaboration position on standardization of metadata
      for dermatologic imaging. Metadata is essential to ensure that dermatologic
      images are properly managed and interpreted. There are two standards-based
      approaches to recording and storing metadata in dermatologic imaging. The first
      uses standard consumer image file formats, and the second is the file format and
      metadata model developed for the Digital Imaging and Communication in Medicine
      (DICOM) standard. DICOM would appear to provide an advantage over using consumer
      image file formats for metadata as it includes all the patient, study, and
      technical metadata necessary to use images clinically. Whereas, consumer image
      file formats only include technical metadata and need to be used in conjunction
      with another actor-for example, an electronic medical record-to supply the
      patient and study metadata. The use of DICOM may have some ancillary benefits in
      dermatologic imaging including leveraging DICOM network and workflow services,
      interoperability of images and metadata, leveraging existing enterprise imaging
      infrastructure, greater patient safety, and better compliance to legislative
      requirements for image retention.

PMID- 29344753
TI  - Comparative Approach of MRI-Based Brain Tumor Segmentation and Classification
      Using Genetic Algorithm.
AB  - The detection of a brain tumor and its classification from modern imaging
      modalities is a primary concern, but a time-consuming and tedious work was
      performed by radiologists or clinical supervisors. The accuracy of detection and
      classification of tumor stages performed by radiologists is depended on their
      experience only, so the computer-aided technology is very important to aid with
      the diagnosis accuracy. In this study, to improve the performance of tumor
      detection, we investigated comparative approach of different segmentation
      techniques and selected the best one by comparing their segmentation score.
      Further, to improve the classification accuracy, the genetic algorithm is
      employed for the automatic classification of tumor stage. The decision of
      classification stage is supported by extracting relevant features and area
      calculation. The experimental results of proposed technique are evaluated and
      validated for performance and quality analysis on magnetic resonance brain
      images, based on segmentation score, accuracy, sensitivity, specificity, and dice
      similarity index coefficient. The experimental results achieved 92.03% accuracy,
      91.42% specificity, 92.36% sensitivity, and an average segmentation score between
      0.82 and 0.93 demonstrating the effectiveness of the proposed technique for
      identifying normal and abnormal tissues from brain MR images. The experimental
      results also obtained an average of 93.79% dice similarity index coefficient,
      which indicates better overlap between the automated extracted tumor regions with
      manually extracted tumor region by radiologists.

PMID- 29344754
TI  - Green and Sustainable Separation of Natural Products from Agro-Industrial Waste:
      Challenges, Potentialities, and Perspectives on Emerging Approaches.
AB  - New generations of biorefinery combine innovative biomass waste resources from
      different origins, chemical extraction and/or synthesis of biomaterials,
      biofuels, and bioenergy via green and sustainable processes. From the very
      beginning, identifying and evaluating all potentially high value-added chemicals
      that could be removed from available renewable feedstocks requires robust,
      efficient, selective, reproducible, and benign analytical approaches. With this
      in mind, green and sustainable separation of natural products from agro
      industrial waste is clearly attractive considering both socio-environmental and
      economic aspects. In this paper, the concepts of green and sustainable separation
      of natural products will be discussed, highlighting the main studies conducted on
      this topic over the last 10 years. The principal analytical techniques (such as
      solvent, microwave, ultrasound, and supercritical treatments), by-products (e.g.,
      citrus, coffee, corn, and sugarcane waste) and target compounds (polyphenols,
      proteins, essential oils, etc.) will be presented, including the emerging green
      and sustainable separation approaches towards bioeconomy and circular economy
      contexts.

PMID- 29344755
TI  - Mathematical modelling of bone adaptation of the metacarpal subchondral bone in
      racehorses.
AB  - In Thoroughbred racehorses, fractures of the distal limb are commonly
      catastrophic. Most of these fractures occur due to the accumulation of fatigue
      damage from repetitive loading, as evidenced by microdamage at the predilection
      sites for fracture. Adaptation of the bone in response to training loads is
      important for fatigue resistance. In order to better understand the mechanism of
      subchondral bone adaptation to its loading environment, we utilised a square root
      function defining the relationship between bone volume fraction [Formula: see
      text] and specific surface [Formula: see text] of the subchondral bone of the
      lateral condyles of the third metacarpal bone (MCIII) of the racehorse, and using
      this equation, developed a mathematical model of subchondral bone that adapts to
      loading conditions observed in vivo. The model is expressed as an ordinary
      differential equation incorporating a formation rate that is dependent on strain
      energy density. The loading conditions applied to a selected subchondral region,
      i.e. volume of interest, were estimated based on joint contact forces sustained
      by racehorses in training. For each of the initial conditions of [Formula: see
      text] we found no difference between subsequent homoeostatic [Formula: see text]
      at any given loading condition, but the time to reach equilibrium differed by
      initial [Formula: see text] and loading condition. We found that the observed
      values for [Formula: see text] from the mathematical model output were a good
      approximation to the existing data for racehorses in training or at rest. This
      model provides the basis for understanding the effect of changes to training
      strategies that may reduce the risk of racehorse injury.

PMID- 29344757
TI  - Should we stop anti-thrombotic agents prior to vitrectomy?

PMID- 29344756
TI  - The Current State of Left Main Percutaneous Coronary Intervention.
AB  - PURPOSE OF REVIEW: While coronary artery bypass grafting (CABG) remains the
      standard of care, advances in stenting technology and procedural technique are
      changing the role of percutaneous coronary intervention (PCI) in the treatment of
      severe left main coronary artery (LMCA) disease. We review contemporary evidence
      comparing PCI and CABG for the treatment of severe LMCA disease, discuss optimal
      techniques during left main PCI, and provide guidance on studied
      revascularization strategies within specific patient subgroups. RECENT FINDINGS:
      Results from randomized control trials of patients treated with PCI or CABG for
      severe LMCA disease demonstrate comparable short- and mid-term rates of death,
      myocardial infarction (MI), and stroke, but increased rates of repeat or target
      vessel revascularization after PCI. Though extended follow-up data has suggested
      lower long-term rates of MI and stroke in patients with severe LMCA disease
      treated with CABG, results from patients undergoing PCI with second-generation
      drug-eluting stents (DES) demonstrate non-inferiority in these outcomes. These
      findings are generalizable to patients with severe LMCA disease having low to
      intermediate anatomic complexity. Intravascular ultrasound and double kissing
      (DK) crush stenting also reduce adverse event rates among patients undergoing
      left main PCI and improve long-term outcomes. In patients with severe LMCA
      disease having low to intermediate anatomic complexity, both CABG and PCI with
      second-generation DES are effective methods of revascularization with comparable
      long-term rates of death, MI, and stroke. The roles of multi-vessel coronary
      artery disease and anatomic complexity on long-term outcomes after CABG or PCI
      for severe LMCA disease remain under investigation.

PMID- 29344758
TI  - Temperature Dependence of Raman-Active In-Plane E2g Phonons in Layered Graphene
      and h-BN Flakes.
AB  - Thermal properties of sp2 systems such as graphene and hexagonal boron nitride (h
      BN) have attracted significant attention because of both systems being excellent
      thermal conductors. This research reports micro-Raman measurements on the in
      plane E2g optical phonon peaks (~ 1580 cm-1 in graphene layers and ~ 1362 cm-1 in
      h-BN layers) as a function of temperature from - 194 to 200  degrees C. The h-BN
      flakes show higher sensitivity to temperature-dependent frequency shifts and
      broadenings than graphene flakes. Moreover, the thermal effect in the c direction
      on phonon frequency in h-BN layers is more sensitive than that in graphene layers
      but on phonon broadening in h-BN layers is similar as that in graphene layers.
      These results are very useful to understand the thermal properties and related
      physical mechanisms in h-BN and graphene flakes for applications of thermal
      devices.

PMID- 29344759
TI  - Mathematical Model of Contractile Ring-Driven Cytokinesis in a Three-Dimensional
      Domain.
AB  - In this paper, a mathematical model of contractile ring-driven cytokinesis is
      presented by using both phase-field and immersed-boundary methods in a three
      dimensional domain. It is one of the powerful hypotheses that cytokinesis happens
      driven by the contractile ring; however, there are only few mathematical models
      following the hypothesis, to the author's knowledge. I consider a hybrid method
      to model the phenomenon. First, a cell membrane is represented by a zero-contour
      of a phase-field implicitly because of its topological change. Otherwise,
      immersed-boundary particles represent a contractile ring explicitly based on the
      author's previous work. Here, the multi-component (or vector-valued) phase-field
      equation is considered to avoid the emerging of each cell membrane right after
      their divisions. Using a convex splitting scheme, the governing equation of the
      phase-field method has unique solvability. The numerical convergence of
      contractile ring to cell membrane is proved. Several numerical simulations are
      performed to validate the proposed model.

PMID- 29344760
TI  - On the Shapley Value of Unrooted Phylogenetic Trees.
AB  - The Shapley value, a solution concept from cooperative game theory, has recently
      been considered for both unrooted and rooted phylogenetic trees. Here, we focus
      on the Shapley value of unrooted trees and first revisit the so-called split
      counts of a phylogenetic tree and the Shapley transformation matrix that allows
      for the calculation of the Shapley value from the edge lengths of a tree. We show
      that non-isomorphic trees may have permutation-equivalent Shapley transformation
      matrices and permutation-equivalent null spaces. This implies that estimating the
      split counts associated with a tree or the Shapley values of its leaves does not
      suffice to reconstruct the correct tree topology. We then turn to the use of the
      Shapley value as a prioritization criterion in biodiversity conservation and
      compare it to a greedy solution concept. Here, we show that for certain
      phylogenetic trees, the Shapley value may fail as a prioritization criterion,
      meaning that the diversity spanned by the top k species (ranked by their Shapley
      values) cannot approximate the total diversity of all n species.

PMID- 29344761
TI  - Construct Validity of the Autism Impact Measure (AIM).
AB  - The Autism Impact Measure (AIM) was designed to track incremental change in
      frequency and impact of core ASD symptoms. The current study examined the
      structural and convergent validity of the AIM in a large sample of children with
      ASD. The results of a series of exploratory and confirmatory factor analyses
      yielded a final model with five theoretically and empirically meaningful
      subdomains: Repetitive Behavior, Atypical Behavior, Communication, Social
      Reciprocity, and Peer Interaction. The final model showed very good fit both
      overall and for each of the five factors, indicating excellent structural
      validity. AIM subdomain scores were significantly correlated with measures of
      similar constructs across all five domains. The results provide further support
      for the psychometric properties of the AIM.

PMID- 29344762
TI  - Capsule commentary on James et al., Impact of a population health management
      intervention on disparities in cardiovascular disease control.

PMID- 29344763
TI  - Visual awareness negativity is an early neural correlate of awareness: A
      preregistered study with two Gabor sizes.
AB  - Electrophysiological recordings are commonly used to study the neural correlates
      of consciousness in humans. Previous research is inconsistent as to whether
      awareness can be indexed with visual awareness negativity (VAN) at about 200 ms
      or if it occurs later. The present study was preregistered with two main aims:
      First, to provide independent evidence for or against the presence of VAN, and
      second, to study whether stimulus size may account for the inconsistent findings.
      Subjects were shown low-contrast Gaussian filtered gratings (Gabor patches) in
      the four visual quadrants. Gabor size (large and small) was varied in different
      sessions and calibrated to each subject's threshold of visual awareness. Event
      related potentials were derived from trials in which subjects localized the
      Gabors correctly to capture the difference between trials in which they reported
      awareness versus no awareness. Bayesian analyses revealed very strong evidence
      for the presence of VAN for both Gabor sizes. However, there was no evidence for
      or against an effect of stimulus size. The present findings provide evidence for
      VAN as an early neural correlate of awareness.

PMID- 29344765
TI  - Parent-child separation: the relationship between separation and psychological
      adjustment among Chinese rural children.
AB  - PURPOSE: The current study aimed to explore the characteristics of psychological
      adjustment among Chinese left-behind children (LBC) in rural areas, and to
      examine the association between separation duration from parent/parents (SDP) and
      children's psychological adjustment and the extent to which personality mediates
      this hypothesized link. METHODS: We surveyed 534 rural children and adolescents
      aged 10-17 years at school (440 LBC and 94 non-LBC) in 2013, who were selected
      for participation using stratified cluster sampling from two counties in
      Chongqing, China. Measures used included socio-demographic variables, age at the
      commencement and end of the separation from parents, the revised Chinese Juvenile
      Eysenck Personality Questionnaire, and the Adolescent Psychological Adaptability
      Scale. RESULTS: Most children (82.4%) had experienced separation from parents. t
      test results showed a marginally significant difference (p = .08) in
      psychological adjustment between LBC (mean = 64.44, SD = 8.62) and non-LBC (mean
      = 66.16, SD = 9.26). LBC's mean SDP was 5.64 years (SD = 3.90). Correlation
      analysis showed that children's SDP was negatively associated with psychological
      adjustment. Structural equation modeling showed that neuroticism, but not
      extraversion or psychoticism, fully mediated the link between children's SDP and
      psychological adjustment. CONCLUSION: Personality (neuroticism) is one of the
      mediating pathways through which long-term SDP may predict poor psychological
      adjustment among children. Given the detrimental impact of long-term SDP,
      interventions should target the mediating pathway to buffer against the negative
      impact of parental separation on the affected rural children and to improve their
      mental health.

PMID- 29344764
TI  - O-GlcNAcylation: key regulator of glycolytic pathways.
AB  - Elevated O-GlcNAcylation is emerging as a general characteristic of most cancers.
      Although O-GlcNAcylation can regulate many cell biological pathways, recent
      evidence suggests that it is a key regulator of metabolic pathways including
      glycolysis in cancer cells. This review summarizes our current understanding of
      how O-GlcNAcylation regulates glycolytic pathways and contributes to alterations
      in cancer cell metabolism.

PMID- 29344766
TI  - Patient-reported symptoms before palliative radiotherapy predict survival
      differences.
AB  - BACKGROUND: Widely used prognostic scores, e. g., for brain or bone metastases,
      are based on disease- and patient-related factors such as extent of metastases,
      age and performance status, which were available in the databases used to develop
      the scores. Few groups were able to include patient-reported symptoms. In our
      department, all patients were assessed with the Edmonton Symptom Assessment
      System (ESAS, a one-sheet questionnaire addressing 11 major symptoms and
      wellbeing on a numeric scale of 0-10) at the time of treatment planning since
      2012. Therefore, we analyzed the prognostic impact of baseline ESAS symptom
      severity. METHODS: Retrospective review of 102 patients treated with palliative
      radiotherapy (PRT) between 2012 and 2015. All ESAS items were dichotomized
      (below/above median). Uni- and multivariate analyses were performed to identify
      prognostic factors for survival. RESULTS: The most common tumor types were
      prostate, breast and non-small cell lung cancer, predominantly with distant
      metastases. Median survival was 6 months. Multivariate analysis resulted in six
      significant prognostic factors. These were ESAS pain while not moving (median 3),
      ESAS appetite (median 5), Eastern Cooperative Oncology Group (ECOG) performance
      status, pleural effusion/metastases, intravenous antibiotics at start or within 2
      weeks before PRT and no systemic cancer treatment. CONCLUSIONS: Stronger pain
      while not moving and reduced appetite (below/above median) predicted
      significantly shorter survival. Development of new prognostic scores should
      include patient-reported symptoms and other innovative parameters because they
      were more important than primary tumor type, age and other traditional baseline
      parameters.

PMID- 29344767
TI  - Klotho attenuates isoproterenol-induced hypertrophic response in H9C2 cells by
      activating Na+/K+-ATPase and inhibiting the reverse mode of Na+/Ca2+-exchanger.
AB  - Cardiac hypertrophy plays a major role in heart failure and is related to patient
      morbidity and mortality. Calcium overloading is a main risk for cardiac
      hypertrophy, and Na+/K+-ATPase (NKA) has been found that it could not only
      regulate intracellular Na+ levels but also control the intracellular Ca2+
      ([Ca2+]i) level through Na+/Ca2+-exchanger (NCX). Recent studies have reported
      that klotho could affect [Ca2+]i level. In this study, we aimed at exploring the
      role of klotho in improving isoproterenol-induced hypertrophic response of H9C2
      cells. The H9C2 cells were randomly divided into control and isoproterenol (ISO)
      (10 MUM) groups. Klotho protein (10 MUg/ml) or NKAalpha2 siRNA was used to
      determine the changes in isoproterenol-induced hypertrophic response. The
      alterations of [Ca2+]i level were measured by spectrofluorometry. Our results
      showed that H9C2 cells which were treated with isoproterenol presented a higher
      level of [Ca2+]i and hypertrophic gene expression at 24 and 48 h compared with
      the control group. Moreover, the expressions of NKAalpha1 and NKAalpha2 were both
      increased in control and ISO groups after treating with klotho protein;
      meanwhile, the NKA activity was increased and NCX activity was decreased after
      treatment. Consistently, the [Ca2+]i level and hypertrophic gene expression were
      decreased in ISO group after klotho protein treatment. However, these effects
      were both prevented by transfecting with NKAalpha2 siRNA. In conclusion, these
      findings demonstrated that klotho inhibits isoproterenol-induced hypertrophic
      response in H9C2 cells by activating NKA and inhibiting the reverse mode of NCX
      and this effect may be associated with the upregulation of NKAalpha2 expression.

PMID- 29344768
TI  - Diagnosis and Treatment of Injuries to the Biceps and Superior Labral Complex in
      Overhead Athletes.
AB  - PURPOSE OF REVIEW: This review discusses the diagnostic and treatment challenges
      presented by injuries to the biceps and superior labral complex. RECENT FINDINGS:
      A focused patient history, numerous physical examination maneuvers, and
      appropriate advanced imaging studies must be utilized to reach an accurate
      diagnosis. Nonoperative management, even in overhead athletes, has demonstrated
      relatively good outcomes, while operative outcomes have yielded mixed results.
      The surgeon must take into account a number of variables when choosing the
      appropriate surgical procedure: labral repair versus biceps tenodesis.
      Rehabilitation, either as nonoperative management or as a postoperative protocol,
      should focus on restoring glenohumeral and scapulothoracic strength, endurance,
      and full, pain-free range of motion, while correcting any deficiencies in balance
      or rhythm throughout the overhead motion. Despite the operative treatment
      challenges that SLAP tears present, with new techniques and proper patient
      selection, overhead athletes with injuries to the biceps and superior labrum
      complex can return to sport at a high level.

PMID- 29344770
TI  - Sub-inner limiting membrane hemorrhage in a patient with Terson syndrome.
AB  - PURPOSE: To report a case of bilateral Terson Syndrome with sub inner limiting
      membrane hemorrhage associated with a rare finding: perimacular fold. METHODS:
      The patient, a 34 years old female with aneurysmal subarachnoid hemorrhage and
      bilateral Terson syndrome was admitted to the Ophthalmology department,
      complaining of blurred vision. Core vitrectomy, hyaloid detachment, peeling of
      the ILM and aspiration of the sub inner limiting membrane hemorrhage was
      performed. Once the inner limiting membrane of the left eye was peeled off, we
      noticed a particular aspect: the perimacular fold. RESULT: Although our patient
      suffered from a massive vitreous haemorrhage the postoperative outcome was
      favorable with a final best corrected visual acuity of 20/30. CONCLUSIONS: In
      patients with billateral Terson syndrome we recommend early surgery, especially
      if the neurological status allows it, a good visual acuity being helpful for the
      neurophysical rehabilitation of the patient.

PMID- 29344769
TI  - Sensitive Synchronous Spectrofluorimetric Study of Certain Sunscreens Using
      Fluorescence Enhancers in Cosmeceutical Formulations.
AB  - Synchronous spectrofluorimetric methods could be successfully adopted for
      simultaneous determination of Octinoxate (OMC), Avobenzone (AVO), Octyltriazone
      (OT), and Phenyl benzimidazole sulfonic acid (PBSA) in moisturizing sunscreen
      lotion, utilizing beta-CD as fluorescence enhancer, and determination of
      Avobenzone (AVO), Homosalate, Tinosorb M and Phenyl benzimidazole sulfonic acid
      (PBSA) in presence of Octocrylene (OCR) in whitening sunscreen cream, using
      micellar medium of Sodium Dodecyl Sulfate (SDS) to enhance fluorescence
      intensity. For first product, zero order synchronous spectrofluorimetric method
      was used for determination of OMC and AVO, and derivative synchronous
      spectrofluorimetric technique was utilized for OT and PBSA in quaternary mixture.
      Linear calibration curves were obtained in a concentration range of 0.5-8 MUg mL-
      1 for OMC and AVO, and in range of 0.05-3 MUg mL- 1 for OT and 0.001-5 MUg mL- 1
      for PBSA, by measuring the fluorescence at 370, 405, 333.2 and 340.6 nm,
      respectively. For second product, first derivative synchronous fluorescence
      method was used for each UV-filter. A linear calibration curves were obtained in
      a concentration range of 0.5-8 MUg mL- 1 for AVO, in range of 0.1-8 MUg mL- 1 for
      Homosalate, 2-10 MUg mL- 1 for Tinosorb M and 0.001-5 MUg mL- 1 for PBSA, by
      measuring the fluorescence at 409.8, 373, 307.2 and 316.8 nm, respectively. The
      detection limits are well below the maximum admissible concentration. The
      proposed methods were validated according to ICH guidelines and successfully
      applied to determine sunscreens in pure form and in Cosmeceutical formulations.
      All the results obtained were compared with those of published methods, where no
      significant difference was observed.

PMID- 29344771
TI  - Enhancing Capacity for Evidence-Based Policymaking: the Role of Economic
      Evaluation Standards.
AB  - This commentary will describe some ongoing activities that are moving the federal
      government toward stronger use of evidence in decision-making. In particular, the
      work of the Commission on Evidence-Based Policymaking points to directions that
      have implications for capacity building and the institutionalization of economic
      evaluation, as well as mechanisms and resources that could make economic
      evaluation more feasible. Bipartisan legislation incorporates many of the
      recommendations of the Commission and reinforces efforts already underway at
      individual agencies as well as among interagency groups. Understanding the
      current context of evidence-based policymaking in the federal government can
      enable economic researchers to better influence the processes of capacity
      building, shape the designs of evaluations, and inform decision-making. The
      commentary highlights areas where further elaboration of economic evaluation
      principles could be useful to support evidence building, implementation, and
      program improvement.

PMID- 29344772
TI  - Safety and efficacy of lamivudine or telbivudine started in early pregnancy for
      mothers with active chronic hepatitis B.
AB  - BACKGROUND: Few data exist regarding use of nucleos(t)ide analogs started in
      early pregnancy for mothers with active chronic hepatitis B (CHB). We assessed
      the safety and efficacy of lamivudine/telbivudine initiated in the first
      trimester versus no treatment in mothers with active CHB. METHODS: We
      retrospectively enrolled 94 mothers newly diagnosed with active CHB in the first
      trimester of pregnancy. Patients with or without antiviral therapy were followed
      until postpartum week 28. All newborns received immunoprophylaxis. The primary
      endpoint was the safety of mothers and infants. The secondary endpoints were
      hepatitis B virus (HBV) DNA suppression and mother-to-child transmission (MTCT)
      rate. RESULTS: Fifty-nine of the 94 mothers initiated lamivudine/telbivudine
      (27/32) in the first trimester of pregnancy; 35 received no treatment. At
      delivery, the viral load reduction was similar between lamivudine and
      telbivudine. Early initiation of lamivudine/telbivudine significantly increased
      the proportion of mothers achieving HBV DNA <106 copies/ml compared with those
      with no treatment (100 versus 42.42 %, p < 0.001). At postpartum week 28, the
      MTCT rate was significant lower in the treated group than in the control group
      (0/61 or 0 versus 4/34 or 11.76 %, p = 0.028). Lamivudine and telbivudine were
      well tolerated in the mothers except mild creatine kinase (CK) elevation. There
      existed no differences in gestational age, infant length and weight, Apgar score,
      adverse events, or birth defect rates between infants from treated and untreated
      mothers. CONCLUSIONS: Treatment with lamivudine or telbivudine for active CHB in
      early pregnancy appears to be safe and effective for controlling maternal disease
      as well as interrupting MTCT.

PMID- 29344773
TI  - Beyond Content: Cultural Perspectives on Using the Internet to Deliver a Sexual
      Health Intervention to American Indian Youth.
AB  - American Indian and Alaska Native (AIAN) youth are characterized by high rates of
      pregnancy and risky sexual behavior. Reaching these youth with culturally
      appropriate interventions is difficult due to geographic dispersion and cultural
      isolation. Online interventions can provide opportunities for reaching and
      engaging AIAN youth. However, electronic interventions are also impersonal and
      this can be culturally incongruous for AIANs and other populations for whom
      traditional ceremonies, practices and patterns of interpersonal communication are
      central. This paper describes the application of community based participatory
      research methods to: (1) identify concerns about the exclusive use of an online
      sexual health program; (2) address community concerns by developing supplemental
      class lessons, and (3) evaluate the feasibility and acceptability of the new
      hybrid intervention. Data derives from qualitative and quantitative sources.
      During the formative phase of the project, qualitative data from partner
      interactions was analyzed with participatory inquiry to inform intervention
      development. To evaluate the intervention, qualitative data (e.g., interviews,
      surveys) were used to understand and explain quantitative measures such as
      implementation fidelity and attendance. Implementers were enthusiastic about the
      hybrid intervention. The lessons were easy to teach and provided opportunities
      for meaningful discussions, adaptations, and community involvement. The use of
      online videos was an effective method for providing training. Working with
      community partners, we resolved cultural concerns arising from the exclusive use
      of the Internet by creating a hybrid intervention. The additional burden for
      staff to deliver the class lessons was considered minimal in comparison to the
      educational and programmatic benefits of the hybrid intervention.
      ClinicalTrials.gov identifier NCT01698073.

PMID- 29344774
TI  - Physiological mechanism of osmoregulatory adaptation in anguillid eels.
AB  - In recent years, the production of eel larvae has dramatic declines due to
      reductions in spawning stocks, overfishing, growth habitat destruction and access
      reductions, and pollution. Therefore, it is particularly important and urgent for
      artificial production of glass eels. However, the technique of artificial
      hatching and rearing larvae is still immature, which has long been regarded as an
      extremely difficult task. One of the huge gaps is artificial condition which is
      far from the natural condition to develop their capability of osmoregulation.
      Thus, understanding their osmoregulatory mechanisms will help to improve the
      breed and adapt to the changes in the environment. In this paper, we give a
      general review for a study progress of osmoregulatory mechanisms in eels from
      five aspects including tissues and organs, ion transporters, hormones, proteins,
      and high throughput sequencing methods.

PMID- 29344775
TI  - New saliva secretion model based on the expression of Na+-K+ pump and K+ channels
      in the apical membrane of parotid acinar cells.
AB  - The plasma membrane of parotid acinar cells is functionally divided into apical
      and basolateral regions. According to the current model, fluid secretion is
      driven by transepithelial ion gradient, which facilitates water movement by
      osmosis into the acinar lumen from the interstitium. The osmotic gradient is
      created by the apical Cl- efflux and the subsequent paracellular Na+ transport.
      In this model, the Na+-K+ pump is located exclusively in the basolateral membrane
      and has essential role in salivary secretion, since the driving force for Cl-
      transport via basolateral Na+-K+-2Cl- cotransport is generated by the Na+-K+
      pump. In addition, the continuous electrochemical gradient for Cl- flow during
      acinar cell stimulation is maintained by the basolateral K+ efflux. However,
      using a combination of single-cell electrophysiology and Ca2+-imaging, we
      demonstrate that photolysis of Ca2+ close to the apical membrane of parotid
      acinar cells triggered significant K+ current, indicating that a substantial
      amount of K+ is secreted into the lumen during stimulation. Nevertheless, the K+
      content of the primary saliva is relatively low, suggesting that K+ might be
      reabsorbed through the apical membrane. Therefore, we investigated the
      localization of Na+-K+ pumps in acinar cells. We show that the pumps appear
      evenly distributed throughout the whole plasma membrane, including the apical
      pole of the cell. Based on these results, a new mathematical model of salivary
      fluid secretion is presented, where the pump reabsorbs K+ from and secretes Na+
      to the lumen, which can partially supplement the paracellular Na+ pathway.

PMID- 29344776
TI  - Dawning of a new era in TRP channel structural biology by cryo-electron
      microscopy.
AB  - Cryo-electron microscopy (cryo-EM) permits the determination of atomic protein
      structures by averaging large numbers of individual projection images recorded at
      cryogenic temperatures-a method termed single-particle analysis. The cryo
      preservation traps proteins within a thin glass-like ice layer, making literally
      a freeze image of proteins in solution. Projections of randomly adopted
      orientations are merged to reconstruct a 3D density map. While atomic resolution
      for highly symmetric viruses was achieved already in 2009, the development of new
      sensitive and fast electron detectors has enabled cryo-EM for smaller and
      asymmetrical proteins including fragile membrane proteins. As one of the most
      important structural biology methods at present, cryo-EM was awarded in October
      2017 with the Nobel Prize in Chemistry. The molecular understanding of Transient
      Receptor-Potential (TRP) channels has been boosted tremendously by cryo-EM single
      particle analysis. Several near-atomic and atomic structures gave important
      mechanistic insights, e.g., into ion permeation and selectivity, gating, as well
      as into the activation of this enigmatic and medically important membrane protein
      family by various chemical and physical stimuli. Lastly, these structures have
      set the starting point for the rational design of TRP channel-targeted
      therapeutics to counteract life-threatening channelopathies. Here, we attempt a
      brief introduction to the method, review the latest advances in cryo-EM structure
      determination of TRP channels, and discuss molecular insights into the channel
      function based on the wealth of TRP channel cryo-EM structures.

PMID- 29344779
TI  - Trigeminal neuropathy in vestibular schwannoma: a treatment algorithm to avoid
      long-term morbidity.
AB  - BACKGROUND: Trigeminal neuropathy (TGN) can occur as a presenting feature of
      vestibular schwannoma (VS) or as an adverse effect of radiosurgery. This study
      was designed to evaluate a treatment algorithm for presenting symptoms of TGN in
      patients with VS, and a new radiosurgery dosimetric tolerance to avoid TGN after
      treatment. Outcome was measured after microsurgery (MS), stereotactic
      radiosurgery (SRS), hypofractionated stereotactic radiotherapy (HSRT), and
      fractionated radiotherapy (FRT). METHODS: A prospectively held VS database was
      retrospectively analysed from 2011 to 2016 at a tertiary university hospital. All
      patients who underwent MS from 2011 and all patients who underwent radiotherapy
      (SRS, HSRT, FRT) from 2015 were studied. Patients on surveillance and
      neurofibromatosis type 2 patients were not included. Patient demographic data,
      tumour characteristics, presenting symptoms, and post-treatment outcomes were
      analysed. RESULTS: Eighty-eight patients were included in the study (43
      microsurgery, 45 radiotherapy). Twenty-seven (31%) patients presented with TGN
      symptoms. The median age of patients included was 56.5 (range 6-72 years), with a
      median follow-up for MS and SRS of 38 and 20 months, respectively (range 10-80
      months). All 27 patients with TGN were offered MS as per protocol. Three patients
      declined, or were not fit for surgery, and received FRT. Complete resolution of
      TGN symptoms was achieved in all 24 patients who underwent MS and 33% (1/3) of
      patients with FRT. Eleven patients experienced transient post-operative
      complications (pseudomeningocele (6), meningitis (3), venous sinus thrombosis,
      cerebellar haemorrhagic contusion, and posterior fossa haematoma). Of the 45
      patients in the radiotherapy cohort, 36 were suitable for SRS, of which 30
      patients who met the dose-volume constraints for trigeminal nerve underwent
      single-fraction SRS and 6 patients who did not meet the constraints received
      HSRT. Nine patients (20%) received FRT including three patients with pre
      treatment TGN. None of the patients developed new TGN symptoms following SRS or
      HSRT. CONCLUSIONS: Our algorithm to select the optimal treatment modality appears
      to achieve comparable or better long-term outcome. Microsurgical resection in our
      cohort resulted in complete resolution of symptoms in all patients. None of our
      SRS- or HSRT-treated patients developed TGN during the follow-up period. The
      adherence to strict trigeminal nerve dose-volume constraints for SRS remains
      critical to minimise TGN post treatment. Fractionated radiotherapy is an
      alternative for patients who refuse surgery or those who are unfit for surgery.

PMID- 29344780
TI  - Intraoperative monitoring of Z-L response (ZLR) and abnormal muscle response
      (AMR) during microvascular decompression for hemifacial spasm. Interpreting the
      role of ZLR.
AB  - BACKGROUND: Z-L response (ZLR) has been suggested to a new electromyographic
      (EMG) potential recorded from the facial muscle of patient with hemifacial spasm
      (HFS) during microvascular decompression (MVD). Although ZLR has been suggested
      to be useful, experience of ZLR monitoring is limited and its significance during
      MVD is still unclear. METHODS: To investigate the significance of ZLR, both ZLR
      and abnormal muscle response (AMR) were simultaneously recorded before and after
      decompression of root exit zone (REZ) in 20 consecutive patients with HFS.
      RESULTS: All 19 AMRs elicited before REZ decompression disappeared immediately
      after decompression of REZ. ZLRs were also observed before decompression of REZ
      in 19 (95%) of 20 patients. Despite negative conversion of AMR after
      decompression in 19 patients, ZLR disappeared in only 13 (68.4%) of 19 patients.
      Among six sustained ZLRs, three showed reduction in the intensity of ZLRs while
      the other three remained unchanged. There were nine cases featuring attachment of
      the distal, non-offending portion of offending vessels to the distal course of
      the facial nerve in addition to attachment to REZ. Negative ZLR conversion and
      presence of peripheral contact of offending vessels to distal facial nerves
      showed significant correlations (p < 0.05). ZLR could be elicited by electrical
      stimulation at non-REZ-offending portion of the offending arterial wall, attached
      to the distal course of the facial nerve. HFS disappeared immediately in all 20
      patients. CONCLUSIONS: Although ZLR might be helpful in cases with multiple
      offenders, interpretation of ZLR needs caution for non-specific transmission of
      electric current through vessel wall to facial nerve.

PMID- 29344777
TI  - Giant Cell Arteritis: Practical Pearls and Updates.
AB  - PURPOSE OF REVIEW: The purpose of this review is to summarize recent updates and
      distill practical points from the literature which can be applied to the care of
      patients with suspected and confirmed giant cell arteritis (GCA). RECENT
      FINDINGS: Contemporary thinking implicates a fundamental failure of T regulatory
      cell function in GCA pathophysiology, representing opportunity for novel
      therapeutic avenues. Tocilizumab has become the first Food and Drug
      Administration-approved treatment for GCA following demonstration of efficacy and
      safety in a phase 3 clinical trial. There have been significant parallel advances
      in both our understanding of GCA pathophysiology and treatment. Tocilizumab, and
      other agents currently under investigation in phase 2 and 3 clinical trials,
      presents a new horizon of hope for both disease remission and avoidance of
      glucocorticoid-related complications.

PMID- 29344778
TI  - The Relationship Between Vancomycin Trough Concentrations and AUC/MIC Ratios in
      Pediatric Patients: A Qualitative Systematic Review.
AB  - BACKGROUND: In adults, the area under the concentration-time curve (AUC) divided
      by the minimum inhibitory concentration (MIC) is associated with better clinical
      and bacteriological response to vancomycin in patients with methicillin-resistant
      Staphylococcus aureus who achieve target AUC/MIC >= 400. This target is often
      extrapolated to pediatric patients despite the lack of similar evidence. The
      impracticalities of calculating the AUC in practice means vancomycin trough
      concentrations are used to predict the AUC/MIC. OBJECTIVE: This review aimed to
      determine the relationship between vancomycin trough concentrations and AUC/MIC
      in pediatric patients. METHODS: We searched the MEDLINE and Embase databases, the
      Cochrane Database of Systematic Reviews, and the Cochrane Central Register of
      Controlled Trials using the medical subject heading (MeSH) terms vancomycin and
      AUC and pediatric* or paediatric*. Articles were included if they were published
      in English and reported a relationship between vancomycin trough concentrations
      and AUC/MIC. RESULTS: Of 122 articles retrieved, 11 met the inclusion criteria.
      One trial reported a relationship between vancomycin trough concentrations,
      AUC/MIC, and clinical outcomes but was likely underpowered. Five studies found
      troughs 6-10 mg/l were sufficient to attain an AUC/MIC > 400 in most general
      hospitalized pediatric patients. One study in patients undergoing cardiothoracic
      surgery found a trough of 18.4 mg/l achieved an AUC/MIC > 400. Two oncology
      studies reported troughs >= 15 mg/l likely attained an AUC/MIC >= 400. In
      critical care patients: one study found a trough of 9 mg/l did not attain the
      AUC/MIC target; another found 7 mg/l corresponded to an AUC/MIC of 400.
      CONCLUSIONS: Potential vancomycin targets varied based on the population studied
      but, for general hospitalized pediatric patients, troughs of 6-10 mg/l are likely
      sufficient to achieve AUC/MIC >= 400. For MIC >= 2 mg/l, higher troughs are
      likely necessary to achieve an AUC/MIC >= 400. More research is needed to
      determine the relationships between vancomycin trough concentrations, AUC/MIC,
      and clinical outcomes.

PMID- 29344781
TI  - Automated 3D Soma Segmentation with Morphological Surface Evolution for Neuron
      Reconstruction.
AB  - The automatic neuron reconstruction is important since it accelerates the
      collection of 3D neuron models for the neuronal morphological studies. The
      majority of the previous neuron reconstruction methods only focused on tracing
      neuron fibres without considering the somatic surface. Thus, topological errors
      often present around the soma area in the results obtained by these tracing
      methods. Segmentation of the soma structures can be embedded in the existing
      neuron tracing methods to reduce such topological errors. In this paper, we
      present a novel method to segment the soma structures with complex geometry. It
      can be applied along with the existing methods in a fully automated pipeline. An
      approximate bounding block is firstly estimated based on a geodesic distance
      transform. Then the soma segmentation is obtained by evolving the surface with a
      set of morphological operators inside the initial bounding region. By evaluating
      the methods against the challenging images released by the BigNeuron project, we
      showed that the proposed method can outperform the existing soma segmentation
      methods regarding the accuracy. We also showed that the soma segmentation can be
      used for enhancing the results of existing neuron tracing methods.

PMID- 29344782
TI  - Accuracy and efficiency of published film dosimetry techniques using a flat-bed
      scanner and EBT3 film.
AB  - Gafchromic EBT3 film is widely used for patient specific quality assurance of
      complex treatment plans. Film dosimetry techniques commonly involve the use of
      transmission scanning to produce TIFF files, which are analysed using a non
      linear calibration relationship between the dose and red channel net optical
      density (netOD). Numerous film calibration techniques featured in the literature
      have not been independently verified or evaluated. A range of previously
      published film dosimetry techniques were re-evaluated, to identify whether these
      methods produce better results than the commonly-used non-linear, netOD method.
      EBT3 film was irradiated at calibration doses between 0 and 4000 cGy and 25
      pieces of film were irradiated at 200 cGy to evaluate uniformity. The film was
      scanned using two different scanners: The Epson Perfection V800 and the Epson
      Expression 10000XL. Calibration curves, uncertainty in the fit of the curve,
      overall uncertainty and uniformity were calculated following the methods
      described by the different calibration techniques. It was found that protocols
      based on a conventional film dosimetry technique produced results that were
      accurate and uniform to within 1%, while some of the unconventional techniques
      produced much higher uncertainties (> 25% for some techniques). Some of the
      uncommon methods produced reliable results when irradiated to the standard
      treatment doses (< 400 cGy), however none could be recommended as an efficient or
      accurate replacement for a common film analysis technique which uses transmission
      scanning, red colour channel analysis, netOD and a non-linear calibration curve
      for measuring doses up to 4000 cGy when using EBT3 film.

PMID- 29344784
TI  - The feasibility and efficacy of pure laparoscopic repeat hepatectomy.
AB  - BACKGROUND: Repeat hepatectomy is often required for hepatocellular carcinoma and
      metastatic tumors. However, this procedure is technically challenging, so
      laparoscopic repeat hepatectomy (LRH) has not been widely adopted. The aim of
      this study was to evaluate the feasibility and efficacy of LRH compared with open
      repeat hepatectomy (ORH) and laparoscopic primary hepatectomy (LPH). METHODS: We
      introduced laparoscopic hepatectomy at our institution in April 2014. We
      performed 127 LPH (LPH group) and 33 LRH procedures (LRH group) from April 2014
      to April 2017; 37 patients underwent ORH from January 2010 to April 2017 (ORH
      group). This study retrospectively compared the patient characteristics and short
      term outcomes of the LRH and ORH groups as well as the LRH and LPH groups.
      RESULTS: There were no conversions to open surgery in the LRH group. In comparing
      the LRH and ORH groups, there were no significant differences in patient
      characteristics except for the type of approach to the previous hepatectomy (p =
      0.004) and indocyanine green retention rate at 15 min (median 12.5 vs. 8.75%, p =
      0.026). The LRH group had less blood loss (median 30 mL vs. 652 mL; p < 0.001),
      less intraoperative transfusion (6.1 vs. 32.4%; p = 0.006), and shorter
      postoperative hospital stays (median 6.5 days vs. 9.0 days; p < 0.001). There
      were no differences with regard to operation time, severe postoperative
      complications, and mortality. In comparing the LRH and LPH groups, there was a
      significant difference only in past history of abdominal surgery (100 vs. 61.4%;
      p < 0.001). In the short-term outcomes, the postoperative hospital stay was
      significantly shorter in the LRH group (median 6.5 days vs. 7 days; p = 0.033),
      and the other results were comparable between the two groups. CONCLUSIONS: LRH is
      feasible and useful for repeat hepatectomy, achieving good short-term outcomes.

PMID- 29344783
TI  - Endoscopic treatment of walled-off pancreatic necrosis complicated with
      pancreaticocolonic fistula.
AB  - BACKGROUND: Pancreaticocolonic fistulas (PCFs) are serious complication of acute
      pancreatitis related with high mortality. The aim of this study was to evaluate
      the efficiency and safety of endoscopic treatment in patients with walled-off
      pancreatic necrosis (WOPN) complicated with PCF. METHODS: This is a retrospective
      analysis of results and complications in the group of 226 patients, who underwent
      endoscopic treatment of symptomatic WOPN between years 2001 and 2016 in the
      Department of Gastroenterology and Hepatology of Medical University of Gdansk.
      RESULTS: PCF was recognized in 21/226 (9.29%) patients. Transmural drainage was
      performed in 20/21 (95.24%) patients. Transpapillary drainage was used in 2/21
      (9.52) patients. The mean time since the start of endotherapy to the diagnosis of
      a fistulas was 9 (3-21) days. Fluoroscopic nasocystic tube-check imaging of an
      existing drain was the initial imaging diagnosis of a PCF in 19/21 (90.48%)
      patients. The mean duration of endoscopic drainage of WOPN was 39.29 (15-87)
      days. Procedure-related adverse events occurred in 10/21 (47.62%) patients and
      most of them were treated conservatively. Three patients required surgical
      treatment. One patient died during endotherapy. The closure of PCF was confirmed
      via imaging in 17/21 (80.95%) patients. The average time since the recognition
      till the closure of PCF was 21 (14-48) days. Complete therapeutic success of WOPN
      complicated with PCF was reached in 16/21 (76.19%) patients. Long-term success of
      endoscopic treatment was achieved in 15/21 (71.43%) patients. CONCLUSIONS:
      Endoscopic treatment of patients with WOPN complicated with PCF is an effective
      method with an acceptable number of complications. The complete regression of the
      WOPN may lead to spontaneous closure of pancreaticocolonic fistulas.

PMID- 29344785
TI  - Laparoscopic intracorporeal rectus aponeuroplasty (LIRA technique): a step
      forward in minimally invasive abdominal wall reconstruction for ventral hernia
      repair (LVHR).
AB  - BACKGROUND: Closing the defect (CD) during laparoscopic ventral hernia repair
      began to be performed in order to decrease seroma, to improve the functionality
      of the abdominal wall, and to decrease the bulging effect. However, tension at
      the incision after CD in large defects is related to an increased rate of pain
      and recurrence. We present the preliminary results of a new technique for medium
      midline hernias as an alternative to conventional CD. METHODS: A prospective
      controlled study was conducted from January 2015 to January 2017 to evaluate an
      elective new procedure (LIRA) performed on patients with midline ventral hernias
      (4-10 cm width). The posterior rectus aponeurosis was opened lengthwise around
      the hernia defect using a laparoscopic approach to create two flaps and was then
      sutured. The size of the flaps was estimated using a mathematical formula. An on
      lay mesh was placed intraperitoneal overlapping the fascia defect. The data
      analyzed included patient demographics, operative parameters, and complications.
      A computerized tomography was performed preoperatively and postoperatively (1
      month and 1 year) to evaluate recurrence, distance between rectus and seroma.
      RESULTS: Twelve patients were included. Mean width of the defect was 5.5 cm.
      Average VAS (24 h) was 3.9, 1.1 (1 month), and 0 (1 year). Mean preoperative
      distance between rectus was 5.5 cm; postoperative was 2.2 cm (1 year).
      Radiological seroma at first month was detected in 50%. Mean follow-up was 15
      months. CONCLUSION: The LIRA technique could be considered as an alternative to
      conventional CD or endoscopic component separation for medium defects under 10 cm
      in width. This technique obtained a "no tension" effect that could be related to
      a lower rate of postoperative pain with no recurrence or bulging, being a safe,
      feasible, and reproducible technique.

PMID- 29344786
TI  - Colonoscopy-induced acute diverticulitis: myth or reality?
AB  - BACKGROUND: Colonoscopy in patients with diverticulosis can be technically
      challenging and limited data exist relating to the risk of post-colonoscopy
      diverticulitis. Our aim was to evaluate the incidence, management, and outcomes
      of acute diverticulitis following colonoscopy. METHODS: Study design is
      retrospective cohort study. Data were gathered by conducting an automated search
      of the electronic patient database using current procedural terminology and ICD-9
      codes. Patients who underwent a colonoscopy from 2003 to 2012 were reviewed to
      find patients who developed acute diverticulitis within 30 days after
      colonoscopy. Patient demographics and colonoscopy-related outcomes were
      documented, which include interval between colonoscopy and diverticulitis,
      colonoscopy indication, simultaneous colonoscopic interventions, and follow-up
      after colonoscopy. RESULTS: From 236,377 colonoscopies performed during the study
      period, 68 patients (mean age 56 years) developed post-colonoscopy diverticulitis
      (0.029%; 2.9 per 10,000 colonoscopies). Incomplete colonoscopies were more
      frequent among patients with a history of previous diverticulitis [n = 10 (29%)
      vs. n = 3 (9%), p = 0.03]. Mean time to develop diverticulitis after colonoscopy
      was 12 +/- 8 days, and 30 (44%) patients required hospitalization. 34 (50%)
      patients had a history of diverticulitis prior to colonoscopy. Among those
      patients, 14 underwent colonoscopy with an indication of surveillance for
      previous disease. When colonoscopy was performed within 6 weeks of a
      diverticulitis attack, surgical intervention was required more often when
      compared with colonoscopies performed after 6 weeks of an acute attack [n = 6
      (100%) vs. n = 10 (36%), p = 0.006]. 6 (9%) out of 68 patients received emergency
      surgical treatment. 15 (24%) out of 62 patients who had non-surgical treatment
      initially underwent an elective sigmoidectomy at a later date. Recurrent
      diverticulitis developed in 16 (23%) patients after post-colonoscopy
      diverticulitis. CONCLUSIONS: Post-colonoscopy diverticulitis is a rare, but
      potentially serious complication. Although a rare entity, possibility of this
      complication should be kept in mind in patients presenting with symptoms after
      colonoscopy.

PMID- 29344787
TI  - A novel fully covered double-bump stent for staple line leaks after bariatric
      surgery: a retrospective analysis.
AB  - BACKGROUND: Staple line leakage after bariatric surgery can be treated by
      endoscopic placement of a self-expandable stent. The success rate of stent
      placement is generally high, but migration is a frequent adverse event that
      hampers successful treatment. The Niti-S Beta stent is a fully covered double
      bump stent that was specifically designed to prevent migration. This study aimed
      to evaluate the effectiveness and adverse event rate of the Niti-S Beta stent.
      METHODS: A retrospective study was performed in three high-volume bariatric
      centers. All consecutive patients between 2009 and 2016 who underwent placement
      of a Beta stent for staple line leakage were included. Primary outcome was
      resolution of the leakage; secondary outcome was the adverse event rate including
      migration. RESULTS: Thirty-eight patients were included. Twenty-five (66%) had
      resolution of the leakage. Success rate was higher in patients who were treated
      with implantation of a Beta stent as initial treatment (100%) than in patients
      who were treated with a stent after revisional surgery had failed (55%, p =
      0.013). Migration occurred in 12 patients (32%). There were two severe adverse
      events requiring surgical intervention, including a bleeding from an aorto
      esophageal fistula. CONCLUSIONS: The success rate and the migration rate of the
      Beta stent seem comparable to other stents in this retrospective study. Despite
      the novel double-bump structure of the stent, the migration rate does not seem to
      be decreased.

PMID- 29344788
TI  - Intracorporeal versus extracorporeal anastomosis after laparoscopic left
      colectomy for splenic flexure cancer: results from a multi-institutional audit on
      181 consecutive patients.
AB  - Although intracorporeal anastomosis has been demonstrated to be safe and
      effective after right colectomy, limited data are available about its efficacy
      after left colectomy for colon cancer located in splenic flexure. A multi
      institutional audit was designed, including 92 patients who underwent
      laparoscopic left colectomy with intracorporeal anastomosis (IA) compared with 89
      matched patients who underwent a laparoscopic left colectomy with extracorporeal
      anastomosis (EA). There was no significant difference in terms of age, sex, BMI,
      and ASA score between the two groups. Post-surgical history and stage of disease
      according to AJCC/UICC TNM were also similar. IA and EA groups demonstrated
      similar oncologic radicality in terms of the number of lymph nodes harvested
      (18.5 +/- 9 vs. 17.5 +/- 8.4; p = 0.48). Recovery after surgery was also better
      in patients who underwent IA, as confirmed by the shorter time to flatus in the
      IA group (2.6 +/- 1.1 days vs. 3.4 +/- 1.2 days; p < 0.001) and higher post
      operative pain expressed in the mean VAS Scale in the EA group (1.7 +/- 2.1 vs.
      3.5 +/- 1.6; p < 0.001). Laparoscopic left colectomy with intracorporeal
      anastomosis was associated with a lower rate of post-operative complications (OR
      6.7, 95% CI 2.2-20; p = 0.001). However, when stratifying according to Clavien
      classification, the difference was consistently confirmed for less severe (class
      I and II) complications (OR 7.6, 95% CI 2.5-23, p = 0.001) but not for class III,
      IV, and V complications (OR 1.8, 95% CI 0.1-16.9; p = 0.59). Our results were
      consistent to hypothesize that a complete laparoscopic approach could be
      considered a safe method to perform laparoscopic left colectomy with the
      advantage of a guaranteed faster recovery after surgery. Further randomized
      clinical trials are needed to obtain a more definitive conclusion.

PMID- 29344789
TI  - Laparoscopic conversion in colorectal cancer surgery; is there any improvement
      over time at a population level?
AB  - Conversion of laparoscopic colorectal cancer resection has been associated with
      worse outcome, but this might have been related to a learning curve effect. This
      study aimed to evaluate incidence, predictive factors and outcomes of
      laparoscopic conversion after the implementation phase of laparoscopic surgery at
      a population level. Patients undergoing elective resection of non-locally
      advanced, non-metastatic colorectal cancer between 2011 and 2015 were included.
      Data were extracted from the Dutch Surgical Colorectal Audit. Patients were
      grouped as laparoscopic completed (LR), laparoscopic converted (CONV) with
      further specification of timing (within or after 30 min) as registered in the
      DSCA, and open resection (OR). Uni- and multi-variate analyses were used to
      determine predictors of conversion and outcome (complicated course and
      mortality), with evaluation of trends over time. A total of 23,044 patients with
      colon cancer and 11,324 with rectal cancer were included. Between 2011 and 2015,
      use of laparoscopy increased from 55 to 84% in colon cancer, and from 49 to 89%
      in rectal cancer. Conversion rates decreased from 11.8 to 8.6% and from 13 to
      8.0%, respectively. Laparoscopic hospital volume was independently associated
      with conversion rate. Only for colon cancer, the rate of complicated course was
      significantly higher after CONV compared to OR (adjusted odds ratio 1.486; 95% CI
      1.298-1.702), and significantly higher after late (> 30 min) compared to early
      conversion (adjusted odds ratio 1.341; 1.046-1.719). There was no impact of CONV
      on mortality in both colon and rectal cancer. The use of laparoscopic colorectal
      cancer surgery increased to more than 80% at a national level, accompanied by a
      decrease in conversion which is significantly related to the laparoscopic
      hospital volume. Conversion was only associated with complicated course in colon
      cancer, especially when the reason for conversion consisted of an intra-operative
      complication, without affecting mortality.

PMID- 29344790
TI  - Prospective analysis of delayed colorectal post-polypectomy bleeding.
AB  - BACKGROUNDS/AIMS: Although post-polypectomy bleeding is the most frequent
      complication after colonoscopic polypectomy, only few studies have investigated
      the incidence of bleeding prospectively. The aim of this study was to investigate
      the incidence of delayed post-polypectomy bleeding and its associated risk
      factors prospectively. METHODS: Patients who underwent colonoscopic polypectomy
      at Kangbuk Samsung Hospital from January 2013 to December 2014 were prospectively
      enrolled in this study. Trained nurses contacted patients via telephone 7 and 30
      days after polypectomy and completed a standardized questionnaire regarding the
      development of bleeding. Delayed post-polypectomy bleeding was categorized as
      minor or major and early or late bleeding. Major delayed bleeding was defined as
      a > 2-g/dL drop in the hemoglobin level, requiring hospitalization for control of
      bleeding or blood transfusion; late delayed bleeding was defined as bleeding
      occurring later than 24 h after polypectomy. RESULTS: A total of 8175
      colonoscopic polypectomies were performed in 3887 patients. Overall, 133 (3.4%)
      patients developed delayed post-polypectomy bleeding. Among them, 90 (2.3%) and
      43 (1.1%) patients developed minor and major delayed bleeding, respectively, and
      39 (1.0%) patients developed late delayed bleeding. In the polyp-based
      multivariate analysis, young age (< 50 years; odds ratio [OR] 2.10; 95%
      confidence interval [CI] 1.18-3.68), aspirin use (OR 2.78; 95% CI 1.23-6.31), and
      polyp size of > 10 mm (OR 2.45; 95% CI 1.38-4.36) were significant risk factors
      for major delayed bleeding, while young age (< 50 years; OR 2.6; 95% CI 1.35
      5.12) and immediate bleeding (OR 3.3; 95% CI 1.49-7.30) were significant risk
      factors for late delayed bleeding. CONCLUSIONS: Young age, aspirin use, polyp
      size, and immediate bleeding were found to be independent risk factors for
      delayed post-polypectomy bleeding.

PMID- 29344791
TI  - SAGES's advanced GI/MIS fellowship curriculum pilot project.
AB  - BACKGROUND: The American health care system faces deficits in quality and
      quantity of surgeons. SAGES is a major stakeholder in surgical fellowship
      training and is responsible for defining the curriculum for the Advanced GI/MIS
      fellowship. SAGES leadership is actively adapting this curriculum. METHODS: The
      process of reform began in 2014 through a series of iterative meetings and
      discussions. A working group within the Resident and Fellow Training Committee
      reviewed case log data from 2012 to 2015. These data were used to propose new
      criteria designed to provide adequate exposure to core content. The working group
      also proposed using video assessment of an MIS case to provide objective
      assessment of competency. RESULTS: Case log data were available for 326 fellows
      with a total of 85,154 cases logged (median 227 per fellow). The working group
      proposed new criteria starting with minimum case volumes for five defined
      categories including foregut (20), bariatrics (25), inguinal hernia (10), ventral
      hernia (10), and solid organ/colon/thoracic (10). Fellows are expected to perform
      an additional 75 complex MIS cases of any category for a total of 150 required
      cases overall. The proposal also included a minimum volume of flexible endoscopy
      (50) and submission of an MIS foregut case for video assessment. The new criteria
      more clearly defined which surgeon roles count for major credit within individual
      categories. Fourteen fellowships volunteered to pilot these new criteria for the
      2017-2018 academic year. CONCLUSIONS: The new SAGES Advanced GI/MIS fellowship
      has been crafted to better define the core content that should be contained in
      these fellowships, while still allowing sufficient heterogeneity so that
      individual learners can tailor their training to specific areas of interest. The
      criteria also introduce innovative, evidence-based methods for assessing
      competency. Pending the results of the pilot program, SAGES will consider broad
      implementation of the new fellowship criteria.

PMID- 29344792
TI  - Post-conditioning hormesis creates a "subtraction to background" disease process:
      biological, aging, and environmental risk assessment implications.
AB  - The interaction of background disease processes with environmental induced
      diseases has long been an issue of considerable interest and debate with respect
      to its impact on risk assessment. Whether and to what extent these processes
      should be considered independent or additive to background has been the principal
      focus of debate. The concept of hormesis, a biphasic dose response characterized
      by a low dose stimulation and a high dose inhibition, as framed within the
      context of post-conditioning, reveal the occurrence of a third type of
      "background" possibility, that of "subtraction to background". This novel
      application of the hormesis concept, which is framed within the biological
      context of post-conditioning adaptive processes, offers considerable implications
      for the assessment of aging and environmental risk assessment.

PMID- 29344793
TI  - The Role of Bone Secreted Factors in Burn-Induced Muscle Cachexia.
AB  - PURPOSE OF REVIEW: Burn injury results in resorptive bone loss, failure to make
      new bone, and muscle protein breakdown resulting in cachexia. The purpose of this
      review is to examine the relationship between bone loss and muscle atrophy in
      burn injury with a view to understanding the process at work and how it may apply
      to other conditions that have similar features. RECENT FINDINGS: We present data
      suggesting that the use of bisphosphonates in the first 10 days following the
      burn prevents not only the resorptive bone loss but also the muscle wasting.
      While an extra-osseous effect of bisphosphonates remains possible, existing
      evidence points to a paracrine effect of bone on maintenance of muscle mass and
      strength. Proposed paracrine factors produced by bone include prostaglandin E2
      and components of the Wnt signaling pathway. TGFbeta may be a bone paracrine
      factor that causes oxidative damage to muscle. In the light of the pattern of
      evidence, burn patients suffer acute resorptive bone loss and muscle wasting.
      This is likely due to the effects of inflammatory cytokines and endogenous
      glucocorticoid production in exacerbating oxidative stress. Early use of
      bisphosphonates can maintain bone mass leading to a paracrine effect of bone in
      the maintenance of muscle mass, although one cannot completely discount a direct
      effect of bisphosphonate on muscle. Because investigators report this
      relationship in a variety of conditions in addition to burns, physicians should
      seriously consider the early use of bisphosphonates to maintain bone and muscle
      mass in a variety of neuromuscular and skeletal diseases.

PMID- 29344794
TI  - Ticagrelor for Secondary Prevention of Atherothrombotic Events After Myocardial
      Infarction: An Evidence Review Group Perspective of a NICE Single Technology
      Appraisal.
AB  - The National Institute for Health and Care Excellence (NICE) invited AstraZeneca,
      the manufacturer of ticagrelor (Brilique(r)), to submit evidence on the clinical
      and cost effectiveness of ticagrelor 60 mg twice daily (BID) in combination with
      low-dose aspirin [acetylsalicylic acid (ASA)] compared with ASA only for
      secondary prevention of atherothrombotic events in patients with a history of
      myocardial infarction (MI) and who are at increased risk of atherothrombotic
      events. Kleijnen Systematic Reviews Ltd (KSR), in collaboration with Maastricht
      University Medical Centre+, was commissioned as the evidence review group (ERG).
      This paper summarises the company submission (CS), the ERG report and the NICE
      guidance produced by the appraisal committee (AC) for the use of ticagrelor in
      England and Wales. The ERG critically reviewed the clinical- and cost
      effectiveness evidence in the CS. The systematic review conducted as part of the
      CS identified one randomised controlled trial (RCT), PEGASUS-TIMI 54. This trial
      reported the time to first occurrence of any event from the composite of
      cardiovascular death, MI and stroke as the primary outcome (hazard ratio 0.84
      ticagrelor 60 mg BID vs. placebo, 95% confidence interval 0.74-0.95). The
      population addressed in the CS was a subgroup of the PEGASUS-TIMI 54 trial
      population, i.e. the 'base-case' population, which comprised patients who had
      experienced an MI between 1 and 2 years ago, whereas the full trial population
      included patients who had experienced an MI between 1 and 3 years ago. While the
      ERG believed the findings of this RCT to be robust, doubts concerning the
      applicability of the trial to UK patients were raised. The company submitted an
      individual patient simulation model to estimate the cost-effectiveness of
      ticagrelor 60 mg BID + ASA versus ASA only. Parametric time-to-event models were
      used to estimate the time to first and subsequent (cardiovascular) events, time
      to treatment discontinuation and time to adverse events. The company's base-case
      analysis resulted in an incremental cost-effectiveness ratio (ICER) of L20,098
      per quality-adjusted life-year (QALY) gained. The main issues surrounding the
      cost effectiveness of ticagrelor 60 mg BID + ASA were the use of parametric time
      to-event models estimated based on the full trial population instead of being
      fitted to the 'label' population (the 'label' population comprised the 'base
      case' population and patients who started ticagrelor 60 mg BID within 1 year of
      previous adenosine diphosphate inhibitor treatment), the incorrect implementation
      of the probabilistic sensitivity analysis (PSA) of the individual patient
      simulation, and simplifications of the model structure that may have biased the
      health benefits and costs estimations of the intervention and comparator. The ERG
      believed the use of the full trial population to inform the parametric time-to
      event models was not appropriate because the 'label' population was the main
      focus of the scope and CS. The ERG could not investigate the magnitude of the
      bias introduced by this assumption. The PSA of the individual patient simulation
      provided unreliable probabilistic results and underestimated the uncertainty
      surrounding the results because it was based on a single patient. The ERG used
      the cohort simulation presented in the cost-effectiveness model to perform its
      base-case and additional analyses and to obtain probabilistic results. The ERG
      amended the company cost-effectiveness model, which resulted in an ERG base-case
      ICER of L24,711 per QALY gained. In its final guidance, the AC recommended
      treatment with ticagrelor 60 mg BID + low-dose ASA for secondary prevention of
      atherothrombotic events in adults who have had an MI and are at increased risk of
      atherothrombotic events.

PMID- 29344797
TI  - Annular dynamics of memo3D annuloplasty ring evaluated by 3D transesophageal
      echocardiography.
AB  - BACKGROUND: We assessed the mitral annular motion after mitral valve repair with
      the Sorin Memo 3D(r) (Sorin Group Italia S.r.L., Saluggia, Italy), which is a
      unique complete semirigid annuloplasty ring intended to restore the systolic
      profile of the mitral annulus while adapting to the physiologic dynamism of the
      annulus, using transesophageal real-time three-dimensional echocardiography.
      METHODS: 17 patients (12 male; mean age 60.4 +/- 14.9 years) who underwent mitral
      annuloplasty using the Memo 3D ring were investigated. Mitral annular motion was
      assessed using QLAB(r)version8 allowing for a full evaluation of the mitral
      annulus dynamics. The mitral annular dimensions were measured throughout the
      cardiac cycle using 4D MV assessment2(r) while saddle shape was assessed through
      sequential measurements by RealView(r). RESULTS: Saddle shape configuration of
      the mitral annulus and posterior and anterior leaflet motion could be observed
      during systole and diastole. The mitral annular area changed during the cardiac
      cycle by 5.7 +/- 1.8%.The circumference length and diameter also changed
      throughout the cardiac cycle. The annular height was significantly higher in mid
      systole than in mid-diastole (p < 0.05). CONCLUSIONS: The Memo 3D ring maintained
      a physiological saddle-shape configuration throughout the cardiac cycle. Real
      time three-dimensional echocardiography analysis confirmed the motion and
      flexibility of the Memo 3D ring upon implantation.

PMID- 29344798
TI  - Association between values of preoperative 6-min walk test and surgical outcomes
      in lung cancer patients with decreased predicted postoperative pulmonary
      function.
AB  - OBJECTIVE: We retrospectively investigated the possibility that the 6-min walk
      test (6MWT) could predict surgical outcomes in lung cancer patients with
      decreased predicted postoperative (ppo) lung function. METHODS: Patients were
      enrolled based on their preoperative spirometry: <60% of the ppo forced
      expiratory volume in 1 s (FEV1.0) or < 60% of the ppo lung carbon monoxide
      diffusion capacity (DLco). Morbidity, oxygen inhalation required > 10 days, home
      oxygen therapy (HOT) requirement, unexpected readmission within 90 days, and 90
      day mortality were included as surgical outcomes. The correlations with walking
      distance and the minimum SpO2 (SpO2min) and maximum decrease in SpO2 (DeltaSpO2)
      during the 6MWT were analyzed using logistic regression analysis, adjusting for
      age, sex, and surgical procedure. RESULTS: Altogether, 121 patients were
      analyzed. Logistic regression analysis revealed that higher DeltaSpO2 and lower
      SpO2min were significantly correlated with a higher risk of prolonged need for
      oxygen inhalation and HOT, surgical morbidity, and 90-day mortality. Cut-off
      values of > 4% for DeltaSpO2 were significant for prolonged oxygen inhalation and
      surgical morbidity. Cut-off values of < 89-91% for SpO2min were also significant
      for the need for prolonged oxygen inhalation, surgical morbidity, and HOT
      requirement. There were no significant correlations between walking distance and
      each surgical outcome. CONCLUSIONS: Oxygen desaturation during 6MWT was a good
      predictor for poor surgical outcomes in lung cancer patients with decreased ppo
      pulmonary function.

PMID- 29344799
TI  - Correction to: Current status of cardiovascular surgery in Japan, 2013 and 2014:
      A report based on the Japan Cardiovascular Surgery database 3. Coronary artery
      bypass surgery.
AB  - In the original publication of this article, Table 4 was published incorrectly.
      The correct Table 4 is given in the following page.

PMID- 29344800
TI  - Platycodon saponins from Platycodi Radix (Platycodon grandiflorum) for the Green
      Synthesis of Gold and Silver Nanoparticles.
AB  - A green synthesis of gold and silver nanoparticles is described in the present
      report using platycodon saponins from Platycodi Radix (Platycodon grandiflorum)
      as reducing agents. Platycodin D (PD), a major triterpenoidal platycodon saponin,
      was enriched by an enzymatic transformation of an aqueous extract of Platycodi
      Radix. This PD-enriched fraction was utilized for processing reduction reactions
      of gold and silver salts to synthesize gold nanoparticles (PD-AuNPs) and silver
      nanoparticles (PD-AgNPs), respectively. No other chemicals were introduced during
      the reduction reactions, providing an entirely green, eco-friendly, and
      sustainable method. UV-visible spectra showed the surface plasmon resonance bands
      of PD-AuNPs at 536 nm and PD-AgNPs at 427 nm. Spherically shaped nanoparticles
      were observed from high-resolution transmission electron microscopy with average
      diameters of 14.94 +/- 2.14 nm for PD-AuNPs and 18.40 +/- 3.20 nm for PD-AgNPs.
      Minor triangular and other polygonal shapes were also observed for PD-AuNPs along
      with spherical ones. Atomic force microscopy (AFM) images also demonstrated that
      both nanoparticles were mostly spherical in shape. Curvature-dependent evolution
      was employed to enhance the AFM images and precisely measure the sizes of the
      nanoparticles. The sizes were measured as 19.14 nm for PD-AuNPs and 29.93 nm for
      PD-AgNPs from the enhanced AFM images. Face-centered cubic structures for both
      nanoparticles were confirmed by strong diffraction patterns from high-resolution
      X-ray diffraction analyses. Fourier transform infrared spectra revealed the
      contribution of -OH, aromatic C=C, C-O, and C-H functional groups to the
      synthesis. Furthermore, the catalytic activity of PD-AuNPs was assessed with a
      reduction reaction of 4-nitrophenol to 4-aminophenol in the presence of sodium
      borohydride. The catalytic activity results suggest the potential application of
      these gold nanoparticles as catalysts in the future. The green strategy reported
      in this study using saponins as reducing agents will pave new roads to develop
      novel nanomaterials with versatile applications.

PMID- 29344801
TI  - Toxoplasma gondii in sympatric domestic and wild ungulates in the Mediterranean
      ecosystem.
AB  - Toxoplasma gondii is a zoonotic protozoan of worldwide distribution. The present
      study provides information on risk factors affecting T. gondii infection in
      domestic and free-ranging wild ungulates sharing habitats in Mediterranean
      ecosystems in Spain. Serum samples from 482 extensively reared domestic ruminants
      and 2351 wild ungulates were tested for T. gondii antibodies using the modified
      agglutination test (MAT, cut-off 1:25). Toxoplasma gondii seroprevalence was
      41.2% of 194 sheep, 18.6% of 199 cattle and 5.6% of 89 goats. The main risk
      factors associated with infection in livestock were the presence of cats, feeding
      on the ground and at stubble fields. In wild ungulates, T. gondii antibodies were
      detected in 10.5% of 1063 red deer, 15.6% of 294 fallow deer, 5.6% of 216
      European mouflon, 5.6% of 90 Spanish ibex, 13.6% of 22 roe deer and 18.6% of 666
      wild boars. The risk factors affecting T. gondii infection in wildlife were
      species, age and hunting season. Significantly higher seroprevalence was found in
      domestic ruminants, particularly in sheep, compared to the wild species tested.
      The present study indicates widespread exposure to T. gondii among domestic and
      wild ungulates in Southern Spain, with significant differences among species
      sharing the same ecosystem. The high seroprevalence observed in domestic
      ruminants, particularly in sheep, reinforces the need for farm management
      practices to control the risk factors associated with T. gondii infection in
      extensively reared livestock. Consumption of raw and undercooked food products
      from domestic and wildlife species may have important implications for public
      health.

PMID- 29344802
TI  - Protein profiling of Acanthamoeba species using MALDI-TOF MS for specific
      identification of Acanthamoeba genotype.
AB  - Acanthamoeba spp. are ubiquitous in the environment and have the potential to
      cause severe infections. The different genotypes of Acanthamoeba have been shown
      to influence the severity of the disease and response to therapy. Characterizing
      Acanthamoeba spp. upto genotype can aid in infection control practices. Twenty
      five Acanthamoeba isolates, characterized by 18S rDNA sequencing, were subjected
      to MALDI-TOF MS analysis by creating a database for the individual genotypes. The
      differentiating features of the various spectra were observed; the coded samples
      were then tested against the created database. The results of identification were
      compared with sequencing. Five different genotypes were obtained-T3, T4, T5, T10,
      and T11. Spectral analysis revealed genus-specific and genotype-specific peaks.
      The peak patterns for individual genotype were discrete and reproducible.
      Clinical isolates produced different peaks from the environmental isolate of the
      same genotype. A concordance of 92% was obtained with MALDI-TOF MS in comparison
      with 18sDNA sequencing. MALDI-TOF MS, once optimized, has the potential to
      reliably identify the genotype of Acanthamoeba spp. and to differentiate clinical
      isolate from mere contaminant.

PMID- 29344803
TI  - Toxoplasma gondii: prevalence and characterization of new genotypes in free-range
      chickens from south Brazil.
AB  - Toxoplasma gondii is an intracellular parasite that can infect all warm-blooded
      animals including humans. Recent studies showed that T. gondii strains from South
      America are genetically diverse. The present work aimed to determine T. gondii
      prevalence in free-ranging chicken in northwest Parana state in Brazil by two
      serological tests, to isolate the parasites from seropositive chickens and to
      genotype the isolates. Antibodies to T. gondii in 386 serum samples from 24 farms
      were investigated by immunofluorescence antibody assay (IFA) and modified
      agglutination test (MAT). Samples having titers >= 16 were considered positive
      for both tests. Among the 386 serum samples, 102 (26.4%) were positive for IFA,
      64 (16.6%) were positive for MAT, 47 (12.2%) were positive in both tests, and 119
      (30.8%) were positive in at least one of the two tests. Brain and pool of heart,
      lung, and liver from the 119 seropositive chickens were used for mouse bioassay
      to isolate the parasites. Thirty eight (31.9%) of these seropositive chickens
      were considered positives in mouse bioassay and 18 isolates were obtained. The
      isolates were characterized by 10 PCR-RFLP genetic markers including SAG1, SAG2
      (5'-3'SAG2, alt.SAG2), SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1, and Apico.
      Results of genotyping were compared with the genotypes in ToxoDB database. It
      revealed ten genotypes, including ToxoDB PCR-RFLP genotypes #6 (n = 2), #19 (n =
      1), #21 (n = 2), #111 (n = 2), #152 (n = 1), and #175 (n = 1) and four new types
      not described before. Our results confirmed a high genetic diversity of this
      parasite in southern Brazil and also showed that the use of two serological tests
      in combination can improve the chance of T. gondii isolation. More studies should
      be taken to determine the zoonotic potential of chickens in the transmission of
      T. gondii.

PMID- 29344804
TI  - Influence of highly concentrated fluoride dentifrices on remineralization
      characteristics of enamel in vitro.
AB  - OBJECTIVES: The aim of this in vitro study was to evaluate the role of highly
      fluoridated dentifrice on remineralization characteristics of lowly and highly
      pre-demineralized enamel artificial caries lesions. METHODS: Bovine enamel
      specimens were prepared (pH 4.95; 21 days) and discriminated in either lowly [L]
      or highly [H] pre-demineralized artificial caries lesions. Specimens with a mean
      DeltaZbaseline,L (95% CI) of 5120 (4995; 5245) vol.% * MUm and a mean
      DeltaZbaseline,H of 8187 (8036; 8339) vol.% * MUm were selected and randomly
      allocated to 12 groups (n = 20). Treatments during pH-cycling (28 days; 6 * 60
      min demineralization/day) were brushing 2*/day with fluoride-free (0 ppm F-
      [L0/H0]), 1100 ppm F- [L1100/H1100], 2800 ppm F- [L2800/H2800], 5000 ppm F-
      [L5000/H5000], 5000 ppm F- + glycerin [L5000 + glycerin/H5000 + glycerin], and
      5000 ppm F- + TCP [L5000 + TCP/H5000 + TCP] containing dentifrices. Dentifrice
      slurries were prepared with deionized water (1:3wt/wt). After cycling specimens
      presenting lesion surface loss were discarded and for the remaining 202
      specimens, transversal microradiographic (TMR) analyses (DeltaZpH-cycle/LDpH
      cycle) were performed again. Changes in mineral loss (DeltaDeltaZ =
      DeltaZbaseline - DeltaZpH-cycle) and lesion depth (DeltaLD = LDbaseline - LDpH
      cycle) were calculated. RESULTS: Significant differences for DeltaDeltaZ could be
      found between L0, L1100, and L5000 as well as H0, H1100, and H2800/H5000 (p <=
      0.01; ANCOVA). Except for 0 ppm F-, higher DeltaDeltaZ could be found in highly
      compared with lowly demineralized specimens (p <= 0.004; ANCOVA). After pH
      cycling, a second lesion front could only be observed in H5000 and H5000 + TCP.
      The correlation between DeltaDeltaZ and F- was moderate for lowly and highly
      demineralized lesions (rL = 0.591; pL < 0.001; rH = 0.746; pH < 0.001),
      indicating a fluoride dose response for both. CONCLUSION: For both baseline
      substrate conditions, a dose response for fluoride could be revealed. CLINICAL
      SIGNIFICANCE: Remineralization characteristics of enamel directly depended on
      baseline mineral loss.

PMID- 29344805
TI  - Salivary biomarkers for oral cancer and pre-cancer screening: a review.
AB  - OBJECTIVE: The objective of the study was to conduct a systematic review of the
      literature assessing potential salivary biomarkers of oral cancer and pre-cancer
      and discuss emerging issues and challenges in relation to oral cancer and pre
      cancer diagnostics. MATERIALS AND METHODS: Search for articles involved the
      Medline, PubMed, and EMBASE. Specific terms were used from January 1995 to March
      2017 by three experts. RESULTS: This search collected 270 articles, of which 105
      articles such as reviews, case reports, news, letter to editor, etc. in first
      round and 117 articles such as publications in other languages than English, non
      human studies, etc. were excluded. The remaining 48 articles considered analyzing
      whole saliva as well as specific gland saliva. Thirty-one studies considered oral
      stimuli such as eating, drinking, and oral hygiene practices for varied periods
      of time prior to sample collection. The time of collection of saliva was morning
      in most studies, but the exact time of collection was not mentioned. Three
      studies showed to have evaluated the whole saliva without centrifugation. Two
      dimensional gel electrophoresis and tandem mass spectrometry were the most
      commonly used methods. Most of the potential salivary biomarkers of oral cancer
      are salivary proteins. CONCLUSION: Combination approach of salivary biomarkers
      could be used as screening tool to improve early detection and diagnostic
      precision of oral pre-cancer and cancer. CLINICAL RELEVANCE: The current findings
      are of importance for clinicians and researchers to mitigate the challenges in
      salivary-based diagnosis of oral cancer and to evaluate reliable, specific, and
      sensitive salivary biomarkers for oral pre-cancer and cancer diagnosis.

PMID- 29344806
TI  - Comparison of two observational methods, scanning electron and confocal laser
      scanning microscopies, in the adhesive interface analysis of endodontic sealers
      to root dentine.
AB  - OBJECTIVES: To compare the accuracy of confocal laser scanning microscopy (CLSM)
      and scanning electron microscopy (SEM) during the analysis of the adhesive
      interface integrity and intratubular penetration of root canal sealers to
      radicular dentine. MATERIALS AND METHODS: Twenty roots of human maxillary
      incisors were prepared and distributed into two groups (n = 10), followed by
      filling with gutta-percha and Endofill (G1) or AH Plus (G2). After 7 days, roots
      were sectioned and analyzed under CLSM and SEM. Score systems were used to
      evaluate the adhesive interface integrity (0-4) and sealer intratubular
      penetration (0-3). Data were submitted to Wilcoxon-Mann-Whitney and Kendall
      correlation statistical tests (alpha = 5%). RESULTS: In the adhesive interface
      analysis, CLSM was similar (P = 0.157) to SEM for Endofill; however, the results
      were different for AH Plus (P = 0.029). Intratubular penetration had significant
      difference between observational methods for both sealers (P < 0.0001).
      Correlation analysis between SEM and CLSM for adhesive interface was moderate for
      Endofill and low for AH Plus. Intratubular penetration was low for both sealers.
      CONCLUSION: SEM and CLSM analysis had similar results when sealers were compared,
      with a more homogeneous adhesive interface, and greater intratubular penetration
      for AH Plus. Comparison between observational methods demonstrated low positive
      correlation for adhesive interface and intratubular penetration analysis.
      CLINICAL RELEVANCE: A proper interface formed between sealer and dentine is very
      important for final quality of root canal filling. Observational methods which
      allow an accurate analysis of this interface must be selected to assess such
      features.

PMID- 29344807
TI  - Inhibition of bone resorption by bisphosphonates interferes with orthodontically
      induced midpalatal suture expansion in mice.
AB  - OBJECTIVES: Craniofacial sutures are important growth sites for skull development
      and are sensitive to mechanical stress. In order to determine the role of bone
      resorption in stress-mediated sutural bone growth, midpalatal suture expansion
      was performed in mice receiving alendronate, an anti-resorptive bisphosphonate.
      MATERIALS AND METHODS: The midpalatal sutures of 8-week-old C57BL/6 mice were
      expanded by orthodontic wires over the period of 2 weeks. Mice with maxillary
      expansion without drug treatment as well as untreated animals served as controls.
      Skulls were analyzed with micro-computed tomography (micro-CT),
      immunohistochemistry and histology. RESULTS: Maxillary expansion in mice without
      drug treatment resulted in an increase of TRAP-positive osteoclasts. In contrast,
      no increase in osteoclasts was observed in expanded sutures of mice with
      bisphosphonate treatment. Double calcein labeling demonstrated rapid bone
      formation on the oral edges of the expanded sutures in mice without
      bisphosphonate treatment. Less bone formation was observed in bisphosphonate
      treated mice after expansion. Histology revealed that the sutural architecture
      was reestablished in expanded sutures of mice without bisphosphonate treatment.
      In contrast, the sutural architecture was disorganized and the cartilage had an
      irregular form, following expansion in bisphosphonate-treated mice. Finally,
      micro-CT imaging demonstrated that the total amount of maxillary expansion was
      significantly lower in mice with bisphosphonate treatment as compared to those of
      mice without drug treatment. CONCLUSIONS: In conclusion, our results indicate
      that osteoclast-mediated bone resorption is needed for maxillary suture expansion
      and reorganization of sutural architecture. CLINICAL SIGNIFICANCE: Orthodontic
      palatal expansion can be complicated in patients with inherited or drug-induced
      diseases of osteoclast dysfunction.

PMID- 29344808
TI  - Minimally Invasive Esophagectomy with Thoracic Duct Resection Post Neoadjuvant
      Chemoradiotherapy for Carcinoma Esophagus-Impact on Lymph Node Yield and
      Hemodynamic Parameters.
AB  - BACKGROUND: Neoadjuvant therapy followed by surgery is the current recommended
      treatment for locally advanced esophageal carcinoma. Thoracic duct (TD) resection
      was indicated for radical mediastinal lymphadenectomy. However, TD resection can
      cause hemodynamic disturbances. The presence of metastasis in TD has not been
      previously studied. METHODS: Twenty-two patients who underwent minimally invasive
      esophagectomy with D2 lymphadenectomy after neoadjuvant chemoradiotherapy for
      esophageal squamous cell carcinoma were analyzed. Ten patients had their TD
      resected from thoracic inlet till the esophageal hiatus. Multiple
      histopathological sections of the TD were examined for evidence of tumor spread.
      Intraoperative and immediate (48 h) postoperative hemodynamic parameters, lymph
      node yield, and postoperative morbidity were compared between TD-resected and TD
      preserved groups. RESULTS: The median postoperative day 1 fluid requirement (3310
      mL vs. 2875 mL, P = 0.059) and the median postoperative day 2 pulse rate were
      higher in the TD-resected group (111/min vs. 95/min, P = 0.043). There was no
      significant difference in the intraoperative fluid infusion, blood loss, urine
      output, mean blood pressure, pulse rate, postoperative urine output, and mean
      blood pressure between two groups. Median (range) mediastinal lymph node count
      was similar in TD-resected and TD-preserved groups [15(11-32) vs. 14(9-31), P =
      0.283]. Pathological examination of TD did not reveal tumor cells in any of the
      patients. There was no significant difference in the postoperative morbidity
      between two groups except for cervical anastomotic dehiscence (P = 0.007).
      CONCLUSIONS: Minimally invasive esophagectomy with TD resection causes minor
      hemodynamic changes in the immediate postoperative period, without adversely
      affecting the postoperative outcome. In the setting of neoadjuvant
      chemoradiotherapy, TD resection does not increase lymph node yield.

PMID- 29344809
TI  - Regeneration of functional alveoli by adult human SOX9+ airway basal cell
      transplantation.
AB  - Irreversible destruction of bronchi and alveoli can lead to multiple incurable
      lung diseases. Identifying lung stem/progenitor cells with regenerative capacity
      and utilizing them to reconstruct functional tissue is one of the biggest hopes
      to reverse the damage and cure such diseases. Here we showed that a rare
      population of SOX9+ basal cells (BCs) located at airway epithelium rugae can
      regenerate adult human lung. Human SOX9+ BCs can be readily isolated by
      bronchoscopic brushing and indefinitely expanded in feeder-free condition.
      Expanded human SOX9+ BCs can give rise to alveolar and bronchiolar epithelium
      after being transplanted into injured mouse lung, with air-blood exchange system
      reconstructed and recipient's lung function improved. Manipulation of lung
      microenvironment with Pirfenidone to suppress TGF-beta signaling could further
      boost the transplantation efficiency. Moreover, we conducted the first autologous
      SOX9+ BCs transplantation clinical trial in two bronchiectasis patients. Lung
      tissue repair and pulmonary function enhancement was observed in patients 3-12
      months after cell transplantation. Altogether our current work indicated that
      functional adult human lung structure can be reconstituted by orthotopic
      transplantation of tissue-specific stem/progenitor cells, which could be
      translated into a mature regenerative therapeutic strategy in near future.

PMID- 29344810
TI  - Dehydroepiandrosterone (DHEA) supplementation: an underappreciated cause of
      premature progesterone elevation detected during frozen embryo transfer.

PMID- 29344811
TI  - Metabolic evolution and a comparative omics analysis of Corynebacterium
      glutamicum for putrescine production.
AB  - Putrescine is widely used in the industrial production of bioplastics,
      pharmaceuticals, agrochemicals, and surfactants. Because the highest titer of
      putrescine is much lower than that of its precursor L-ornithine reported in
      microorganisms to date, further work is needed to increase putrescine production
      in Corynebacterium glutamicum. We first compared 7 ornithine decarboxylase genes
      and found that the Enterobacter cloacae ornithine decarboxylase gene speC1 was
      most suitable for putrescine production in C. glutamicum. Increasing NADPH
      availability and blocking putrescine oxidation and acetylation were chosen as
      targets for metabolic engineering. The putrescine producer C. glutamicum PUT4 was
      first constructed by deleting puo, butA and snaA genes, and replacing the fabG
      gene with E. cloacae speC1. After adaptive evolution with C. glutamicum PUT4, the
      evolved strain C. glutamicum PUT-ALE, which produced an 96% higher amount of
      putrescine compared to the parent strain, was obtained. The whole genome
      resequencing indicates that the SNPs located in the odhA coding region may be
      associated with putrescine production. The comparative proteomic analysis reveals
      that the pentose phosphate and anaplerotic pathway, the glyoxylate cycle, and the
      ornithine biosynthetic pathway were upregulated in the evolved strain C.
      glutamicum PUT-ALE. The aspartate family, aromatic, and branched chain amino acid
      and fatty acid biosynthetic pathways were also observed to be downregulated in C.
      glutamicum PUT-ALE. Reducing OdhA activity by replacing the odhA native start
      codon GTG with TTG and overexpression of cgmA or pyc458 further improved
      putrescine production. Repressing the carB, ilvH, ilvB and aroE expression via
      CRISPRi also increased putrescine production by 5, 9, 16 and 19%, respectively.

PMID- 29344812
TI  - Short-term and long-term effects of osteoporosis on incisor teeth and femoral
      bones evaluated by Raman spectroscopy and energy dispersive X-ray analysis in
      ovariectomized rats.
AB  - There are few published data on the relationship between loss of bone mass due to
      osteoporosis and poor tooth quality. This study analyzed the effects of
      osteoporosis on incisor teeth and femoral bones using optical techniques in rats.
      Twenty female Wistar rats aged 6 months (n = 20) were randomized into two groups:
      control group, non-ovariectomized rats (n = 10); ovariectomy group,
      ovariectomized rats to induce osteoporosis (n = 10). Each group was subdivided
      randomly into two groups containing five rats each as follows. Control group 1:
      non-ovariectomized rats euthanized at the age of 9 or 3 months post-ovariectomy
      (n = 5); Control group 2: non-ovariectomized rats euthanized at the age of 1 year
      or 6 months post-ovariectomy (n = 5); ovariectomy group 1: ovariectomized rats
      euthanized at the age of 9 months or 3 months post-ovariectomy (n = 5);
      ovariectomy group 2: ovariectomized rats euthanized at the age of 1 year or 6
      months post-ovariectomy (n = 5). The incisor teeth and femoral bones of Wistar
      rats were removed to perform Raman spectroscopy using an excitation laser at 785
      nm. In addition, an energy-dispersive X-ray spectrometer system was used to
      evaluate calcium (Ca) and phosphorus (P). The main findings included significant
      changes (p < 0.05) for phosphate and carbonate band areas for both incisor teeth
      and femur bones. In addition, there was significant negative correlation between
      the P concentration and phosphate/carbonate ratio (lower P content-larger ratio,
      p < 0.05) for incisor teeth and femoral bones. The proline and CH2 wag band areas
      were significantly reduced only for the incisor teeth (p < 0.05). Therefore,
      Raman spectroscopy assessed the compositional, physicochemical and structural
      changes in hard tissue. The current study also pointed out the possible action
      mechanisms of these changes, bone fracture risk and dental fragility. It is
      important to emphasize that poor dental quality may also occur due to
      osteoporosis.

PMID- 29344813
TI  - Stroke volume variation and serum creatinine changes during abdominal aortic
      aneurysm surgery: a time-integrated analysis.
AB  - BACKGROUND: Patients undergoing abdominal aortic aneurysm (AAA) surgery with
      suprarenal clamping are at high risk for acute kidney injury (AKI) and major
      cardiac and cerebrovascular events (MACCE). We aimed to assess whether the stroke
      volume variation (SVV), a measure of hemodynamic instability, is associated with
      AKI in hypertensive patients undergoing elective AAA surgery with suprarenal
      clamping. METHODS: In a cohort of 51 hypertensive patients, we performed serial
      measurements of SVV (n = 459) and serum creatinine (sCr) (n = 255). AKI was
      defined according to the KDIGO clinical practice guidelines. Data were analyzed
      by repeated-measures ANOVA and regression analysis of time-integrated changes of
      both SVV and sCr. RESULTS: AKI developed in 45% of patients (stage 1: 31%; stage
      2: 10%; stage 3: 2%). The diuresis during surgery (beta - 0.29 Z-score 95% [CI -
      0.54, - 0.05]; p = 0.02), clamp time (beta 0.29 Z-score [0.05-0.52]; p = 0.02),
      and time-integrated changes in SVV from baseline to 12 h after surgery (beta 0.31
      Z-score [0.03-0.60]; p = 0.03) were independent predictors of the time-integrated
      changes in sCr from baseline to 48 h after the end of surgery. In a model
      adjusted for age and sex, patients with AKI had an increased risk for MACCE
      during a mean follow-up of 3.5 +/- 1.1 years (HR 5.53 [1.52-20.06]; p = 0.004).
      CONCLUSIONS: SVV increases progressively during and after AAA surgery in subjects
      who will develop AKI. The increase of SVV precedes and predicts the rise in sCr
      and is a good discriminator of the development of AKI. AKI is associated with an
      increased long-term risk for MACCE.

PMID- 29344814
TI  - Nutritional therapy in autosomal dominant polycystic kidney disease.
AB  - CKD-related nutritional therapy (NT) is a crucial cornerstone of CKD patients'
      treatment, but the role of NT has not been clearly investigated in autosomal
      dominant polycystic kidney disease (ADPKD). Several clinical studies have focused
      on new pharmacological approaches to delay cystic disease progression, but there
      are no data on dietary interventions in ADPKD patients. The aim of this paper is
      to analyze the evidence from the literature on the impact of five nutritional
      aspects (water, sodium, phosphorus, protein intake, and net acid load) in CKD
      related ADPKD extrapolating-where information is unavailable-from what occurs in
      CKD non-ADPKD patients Sodium intake restriction could be useful in decreasing
      the growth rate of cysts. Although further evidence is needed, restriction of
      phosphorus and protein intake restriction represent cornerstones of the dietary
      support of renal non-ADPKD patients and common sense can guide their use. It
      could be also helpful to limit animal protein, increasing fruit and vegetables
      intake together with a full correction of metabolic acidosis. Finally, fluid
      intake may be recommended in the early stages of the disease, although it is not
      to be prescribed in the presence of moderate to severe reduction of renal
      function.

PMID- 29344815
TI  - Comment on: "Genetic Variants and Anterior Cruciate Ligament Rupture: A
      Systematic Review".

PMID- 29344816
TI  - Author's Reply to Lv: Comment on: "Genetic Variants and Anterior Cruciate
      Ligament Rupture: A Systematic Review".

PMID- 29344817
TI  - The Content of Mercury in Herbal Dietary Supplements.
AB  - The dietary supplement market in Poland has been growing rapidly, and the number
      of registered products and their consumption increases steadily. Among the most
      popular and the easiest to get are herbal supplements, available in any
      supermarket. The aim of this paper was to investigate the mercury content in the
      herbal supplements. The dietary supplements that have been examined (24) are
      available on the Polish market and contain one or more herbal ingredients.
      Supplements were pulverized in porcelain mortar and identified by AMA 254 atomic
      absorption spectrometer. The range of variations for all tested supplements was
      within 0.02-4293.07 MUg/kg. The arithmetic mean of the total result was 193.77
      MUg/kg. A higher mercury content then this mean was found in preparations-bamboo
      shoots and alga Chlorella pyrenoidosa. The studies have shown that mercury is
      present in every examined herbal supplement, and its content exceeds in two
      preparations (with bamboo and alga) the permissible limit of 0.10 mg/kg. There
      were statistically significant differences in the occurrence of mercury depending
      on the herbal ingredient in the supplement. The lowest content was found in the
      preparation with Tanacetum parthenium and the highest with bamboo shoots. The
      mercury content in the tested herbal supplements was statistically significant in
      the form of a supplement-a tablet and a capsule. Daily, weekly, monthly, and
      yearly consumption of mercury with examined supplements was calculated-the
      results did not exceed the PTWI-provisional tolerable weekly intake of mercury.
      To increase consumer safety, it is imperative to conduct further research on
      dietary supplements and implement a stricter quality control of the dietary
      supplements.

PMID- 29344818
TI  - Dietary Chromium Picolinate Supplementation Affects Growth, Whole-Body
      Composition, and Gene Expression Related to Glucose Metabolism and Lipogenesis in
      Juvenile Blunt Snout Bream, Megalobrama amblycephala.
AB  - An 11-week feeding trial was carried out to investigate the effects of
      supplemented chromium picolinate (Cr-Pic) on the growth, whole-body composition,
      and relative mRNA expression related to lipogenesis and glucose metabolism in
      juvenile blunt snout bream. Seven isonitrogenous and isoenergetic diets with
      graded Cr supplementation levels were fed to triplicate groups. The final weight
      (FW), feed conversion ratio (FCR), and specific growth rate (SGR) were improved
      with increasing dietary Cr supplementation levels up to 0.4 mg/kg, and thereafter
      showed relatively constant. However, 12.0 mg/kg dietary Cr supplementation
      decreased growth and feed utilization. Based on SGR and FCR, the optimal dietary
      Cr supplementation level for the juvenile was estimated to be 0.28 mg/kg.
      Significantly higher plasma insulin levels were found in juvenile fed diets with
      0.4 and 0.8 mg/kg Cr supplementation compared to those fed diet sans supplemented
      Cr. Plasma glucose levels decreased with increasing dietary Cr supplementation,
      and the lowest value was remarked in the group added 3.2 mg/kg of Cr. Adding 0.4
      0.8 mg/kg Cr enhanced insulin receptor substrate 1 (IRS-1), phosphoinositide-3
      kinase (PI3K), and pyruvate kinase (PK) and inhibited expression of
      phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G6Pase), and
      glycogen synthase (GS) mRNA levels. High dietary Cr (12.0 mg/kg) supplementation
      resulted in high G6Pase and PEPCK expression. The highest content of whole-body
      lipid was remarked in fish fed with 0.4 mg/kg dietary Cr, which related to the
      enhanced gene expression related to lipogenesis; thereafter, mRNA levels showed a
      diminishing trend. These findings indicate that optimum dietary Cr-Pic
      supplementation has a positive effect on growth and blood glucose homeostasis by
      modifying the mRNA levels related to glucose metabolism and lipogenesis in
      juvenile blunt snout bream.

PMID- 29344820
TI  - Metastases from distant primary tumours on the head and neck: clinical
      manifestation and diagnostics of 91 cases.
AB  - PURPOSE: The aim of this study was to evaluate which primary tumours metastasize
      on the head and neck region, identify the kind of clinical manifestation, the
      types of diagnostics that should be performed, and prove that the therapy appears
      possible and useful. PATIENTS: As many as 91 patients with a distant metastasis
      on the head and neck were enrolled in this retrospective clinical study from
      January 2004 to September 2016. All the patients were evaluated for clinical
      symptoms, primary tumour, localization, diagnostics, and surgical procedure.
      RESULTS: A total of 31 patients had asymptomatic swelling, 27 patients had
      symptomatic swelling, and nine experienced isolated pain without swelling. Most
      other symptoms were organ-specific. The most frequent localizations were the
      orbit (44 metastases), mandible (19), neck region (9), and skin (7). The most
      common primary tumours were breast carcinoma (44), bronchial carcinoma (12), and
      renal carcinoma (9). A biopsy was performed on 38 patients, a partial resection
      was done on 28 patients, extirpation on six patients, and a radical resection on
      19 patients. CONCLUSION: Distant metastases on the head and neck are rare and,
      therefore, pose a challenge for the oncologist and other involved disciplines.
      Most distant metastases occur within the first five years. Late metastases,
      especially in breast carcinoma, are still possible after 20 years. A surgical
      examination should be carried out if the findings are not clear due to multiple
      differential diagnoses. In particular, surgical options under palliative aspects
      should be examined.

PMID- 29344821
TI  - Resistance of four fixation techniques used to treat subcondylar fractures.
AB  - OBJECTIVE: This study aimed to evaluate the resistance of four fixation
      techniques used to treat subcondylar fractures. The following techniques were
      evaluated: fixation with one 4-hole single straight plate; fixation with one 2-mm
      4-hole system plate and one 1.5-mm 3-hole system plate; fixation with two 2-mm
      plates with a 3-hole anterior plate; and fixation with two 2-mm plates with four
      holes each. STUDY DESIGN: Each fixation technique was subjected to a resistance
      test. The load values were measured when displacement of 1, 2, and 5 mm was
      reached. Load values were compared for statistically significant differences
      using analysis of variance (ANOVA; p < 0.5) and Tukey's test. RESULTS:
      Statistically significant differences were observed, when the load was applied to
      the first molar on the side of the fracture. The group treated with a 4-hole, 2
      mm, one plate system showed resistance to lower load values than the groups
      treated with two plates in any combination. CONCLUSIONS: When the fracture was
      fixed using two plates, regardless of the kind of plates used, no statistically
      significant difference between the groups was observed. However, two plate
      systems showed better resistance than one plate systems.

PMID- 29344822
TI  - Novel oral anticoagulants in the preoperative period: a meta-analysis.
AB  - The purpose of this study is to evaluate the efficacy and safety of novel oral
      anticoagulant (NOAC) versus warfarin therapy in patients undergoing different
      operations. We performed a systematic review of MEDLINE, EMBASE, Cochrane
      Controlled Trials Register, and reports presented at scientific meetings. The
      efficacy and safety of NOACs during the perioperative period was compared to that
      using warfarin. Of the 2652 studies initially reviewed, we identified 9 that
      included 15,880 patients for the meta-analysis. Compared to warfarin, dabigatran
      increased the risk of major bleeding (RR 1.37, 95% CI 1.06-1.78, P = 0.02).
      Apixaban (RR 0.63, 95% CI 0.40-0.99, P = 0.04) reduced thrombotic events. NOAC
      therapy decreased thrombotic events in patients undergoing non-cardiac surgery
      (RR 0.68, 95% CI 0.50-0.92, P = 0.02). Compared to warfarin, the administration
      of NOACs in the perioperative period has the same risk of thromboembolism and
      major bleeding. But patients undergoing non-cardiac surgery may benefit more from
      perioperative NOAC therapy. Apixaban may reduce thrombotic events and dabigatran
      increases the risk of major bleeding during the perioperative period.

PMID- 29344823
TI  - Long-term visual outcomes of craniopharyngioma in children.
AB  - Visual function is a critical factor in the diagnosis, monitoring, and prognosis
      of craniopharyngiomas in children. The aim of this study was to report the long
      term visual outcomes in a cohort of pediatric patients with craniopharyngioma.
      The study design is a retrospective chart review of craniopharyngioma patients
      from a single tertiary-care pediatric hospital. 59 patients were included in the
      study. Mean age at presentation was 9.4 years old (range 0.7-18.0 years old). The
      most common presenting features were headache (76%), nausea/vomiting (32%), and
      vision loss (31%). Median follow-up was 5.2 years (range 1.0-17.2 years). During
      follow-up, visual decline occurred in 17 patients (29%). On Kaplan Meier survival
      analysis, 47% of the cases of visual decline occurred within 4 months of
      diagnosis, with the remaining cases occurring sporadically during follow-up (up
      to 8 years after diagnosis). In terms of risk factors, younger age at diagnosis,
      optic nerve edema at presentation, and tumor recurrence were found to have
      statistically significant associations with visual decline. At final follow-up,
      58% of the patients had visual impairment in at least one eye but only 10% were
      legally blind in both eyes (visual acuity 20/200 or worse or < 20 degrees  of
      visual field). Vision loss is a common presenting symptom of craniopharyngiomas
      in children. After diagnosis, monitoring vision is important as about 30% of
      patients will experience significant visual decline. Long-term vision loss occurs
      in the majority of patients, but severe binocular visual impairment is uncommon.

PMID- 29344824
TI  - Brucellosis Risk in Urban and Agro-pastoral Areas in Tanzania.
AB  - Epidemiology of human and animal brucellosis may depend on ecological conditions.
      A cross-sectional study was conducted to compare prevalence and risk factors of
      bovine brucellosis, and risky behaviours for the human infection between urban
      and agro-pastoral areas in Morogoro region, Tanzania. Cattle blood sampling and
      interviews using a structured questionnaire were conducted with farmers. Rose
      Bengal test was conducted for the cattle sera, and positive samples were
      confirmed with competitive ELISA. Farm-level sero-prevalences were 0.9% (1/106,
      95% CI 0.0-5.9%) and 52.9% (9/17, 95% CI 28.5-76.1%) in urban and agro-pastoral
      areas, respectively. The animal-level-adjusted prevalences were 0.2% (1/667, 95%
      CI 0.0-1.1%) and 7.0% (28/673, 95% CI 5.7-8.4%) in those areas. The final farm
      level model including both areas found two risk factors: history of abortion in
      the herd (P < 0.01) and cattle grazing (P = 0.07). The animal-level risk factors
      in agro-pastoral areas were age (P = 0.04) and history of abortion (P = 0.03). No
      agro-pastoral farmer knew about Brucella vaccine. Agro-pastoralists generally had
      poorer knowledge on brucellosis and practiced significantly more risky behaviours
      for human brucellosis such as drinking raw milk (17.6%, P < 0.01) and blood
      (35.3%, P < 0.01), and helping cattle birth (100%, P = 0.04) than urban farmers
      (0, 0 and 79.2%, respectively). Intervention programs through education including
      both human and animal health particularly targeting agro-pastoralists would be
      needed.

PMID- 29344825
TI  - The Voltage-Dependent Anion Channel (VDAC) of Pacific Oysters Crassostrea gigas
      Is Upaccumulated During Infection by the Ostreid Herpesvirus-1 (OsHV-1): an
      Indicator of the Warburg Effect.
AB  - Voltage-dependent anion channel (VDAC) is a key mitochondrial protein. VDAC
      drives cellular energy metabolism by controlling the influx and efflux of
      metabolites and ions through the mitochondrial membrane, playing a role in its
      permeabilization. This protein exerts a pivotal role during the white spot
      syndrome virus (WSSV) infection in shrimp, through its involvement in a
      particular metabolism that plays in favor of the virus, the Warburg effect. The
      Warburg effect corresponds to an atypical metabolic shift toward an aerobic
      glycolysis that provides energy for rapid cell division and resistance to
      apoptosis. In the Pacific oyster Crassostrea gigas, the Warburg effect occurs
      during infection by Ostreid herpesvirus (OsHV-1). At present, the role of VDAC in
      the Warburg effect, OsHV-1 infection and apoptosis is unknown. Here, we developed
      a specific antibody directed against C. gigas VDAC. This tool allowed us to
      quantify the tissue-specific expression of VDAC, to detect VDAC oligomers, and to
      follow the amount of VDAC in oysters deployed in the field. We showed that
      oysters sensitive to a mortality event in the field presented an accumulation of
      VDAC. Finally, we propose to use VDAC quantification as a tool to measure the
      oyster susceptibility to OsHV-1 depending on its environment.

PMID- 29344826
TI  - Phytochemical Analysis and Evaluation of the Antioxidant, Anti-Inflammatory, and
      Antinociceptive Potential of Phlorotannin-Rich Fractions from Three Mediterranean
      Brown Seaweeds.
AB  - Phlorotannins, phenolic compounds produced exclusively by seaweeds, have been
      reported to possess various pharmacological properties. However, there have been
      few works on these compounds from Mediterranean seaweeds. In this study, we
      investigated the phytochemical analysis and pharmacological potential of
      phlorotannin-rich fractions from three brown seaweeds collected along the Tunisia
      coast: Cystoseira sedoides (PHT-SED), Cladostephus spongeosis (PHT-CLAD), and
      Padina pavonica (PHT-PAD). Phytochemical determinations showed considerable
      differences in total phenolic content (TPC) and phlorotannin content (PHT). The
      highest TPC level (26.45 mg PGE/g dry material (Dm)) and PHT level (873.14 MUg
      PGE/g Dm) were observed in C. sedoides. The antioxidant properties of these three
      fractions assessed by three different methods indicated that C. sedoides
      displayed the highest total antioxidant activity among the three species (71.30
      mg GAE/g Dm), as well as the free radical scavenging activity with the lowest
      IC50 value in both DPPH (27.7 MUg/mL) and ABTS (19.1 MUg/mL) assays. Furthermore,
      the pharmacological screening of the anti-inflammatory potential of these
      fractions using in vivo models, in comparison to reference drugs, established a
      remarkable activity of PHT-SED at the dose of 100 mg/kg; the inhibition
      percentages of ear edema in mice model and paw edema in rats model were of 82.55
      and 81.08%, respectively. The content of malondialdehyde (MDA) in liver tissues
      has been quantified, and PHT-SED was found to remarkably increase the lipid
      peroxidation in rat liver tissues. In addition, in two pain mice models, PHT-SED
      displayed a profound antinociceptive activity at 100 mg/kg and has proved a
      better analgesic activity when used in combination with the opioid drug,
      tramadol.

PMID- 29344828
TI  - Neuroprotective effect of p-coumaric acid in mice with cerebral ischemia
      reperfusion injuries.
AB  - Cerebral ischemia reperfusion (IR) is associated with neuronal death, which leads
      to disability and cognitive decline. The pathomechanism occurs because ischemia
      is exacerbated during the reperfusion period. Neuronal damage susceptibility
      depends on the affected brain areas and the duration of ischemia. Prevention and
      supplementation to neurons may help them endure during IR and further benefit
      them in rehabilitation. We investigated the protective effect of p-coumaric acid
      (PC) on cerebral IR injuries in mice. We randomly divided 30 male ICR mice into 3
      groups of Sham (received vehicle and not induced IR), Control-IR (received
      vehicle and induced IR) and PC-IR (received 100 mg/kg PC and induced IR). We
      orally administered vehicle or 100 mg/kg of p-coumaric acid for 2 weeks before
      inducing the cerebral IR injuries by using 30 min of a bilateral common carotid
      artery occlusion followed by a 45-min reperfusion. We induced the IR condition in
      the Control-IR and PC-IR groups but not the Sham group, and only the PC-IR group
      received p-coumaric acid. After IR induction, we sacrificed all the mice and
      collected their brain tissues to evaluate their oxidative statuses, whole brain
      infarctions and vulnerable neuronal deaths. We studied the whole-brain infarction
      volume by 2, 3, 5-triethyltetrazoliumchloride staining of sections. We performed
      a histological investigation of the vulnerable neuronal population in the dorsal
      hippocampus by staining brain sections with 0.1% cresyl violet. The results
      indicated that IR caused significant increases in calcium and malondialdehyde
      (MDA) levels, whole brain infarction volume and hippocampal neuronal death.
      Pretreatment with p-coumaric acid significantly reduced MDA levels, whole-brain
      infarction volume and hippocampal neuronal death together and increased catalase
      and superoxide dismutase activities. We conclude here that pretreating animals
      with p-coumaric acid can prevent IR-induced brain oxidative stress, infarction
      size and neuronal vulnerability to death in cerebral IR injuries.

PMID- 29344829
TI  - Rapid-acting and Regular Insulin are Equal for High Fat-Protein Meal in
      Individuals with Type 1 Diabetes Treated with Multiple Daily Injections.
AB  - INTRODUCTION: The fat and protein content can impact late postprandial glycemia;
      therefore, prolonged insulin boluses for high-fat/-protein meals are recommended
      for patients with type 1 diabetes on insulin pump therapy. It is not clear how to
      translate these findings to multiple daily injection (MDI) therapy. We
      hypothesized that regular insulin with a slower onset and a longer duration of
      action might be advantageous for such meals. METHODS: Twenty-five patients with
      well-controlled type 1 diabetes (mean HbA1c 6.8%, 51 mmol/mol, no episodes of
      hypoglycemia) on MDI therapy, aged 27.9 +/- 4.3 years and well trained in
      flexible intensive insulin therapy, were given three test breakfasts with the
      same carbohydrate (CHO) content. The amount of fat and protein was low (LFP) or
      high (HFP). For LFP meals, patients received a rapid-acting insulin; for HFP
      meals, a rapid-acting or regular insulin was given in individual doses according
      to the CHO content and individual insulin-CHO ratios. Postprandial glycemia was
      determined by 6-h continuous glucose monitoring. RESULTS: Acute postprandial
      glucose levels measured for 2 h were similar after LFP and two HFP meals (7.8 +/-
      2.0, 8.1 +/- 2.1, 8.0 +/- 1.9 mmol/l). Late postprandial glycemia measured from 2
      to 6 h was significantly lower after the LFP meal (6.7 +/- 1.8 mmol/l, p < 0.05)
      than after the HFP meals, but there was no difference between the rapid-acting or
      regular insulin on HFP days (8.6 +/- 2.6 and 8.9 +/- 2.8 mmol/l, NS). CONCLUSION:
      The preliminary results of this study indicate no benefit to cover fat-protein
      meals with regular insulin in individuals with type 1 diabetes treated with MDI.

PMID- 29344827
TI  - Molecular imaging of cardiac remodelling after myocardial infarction.
AB  - Myocardial infarction and subsequent heart failure is a major health burden
      associated with significant mortality and morbidity in western societies. The
      ability of cardiac tissue to recover after myocardial infarction is affected by
      numerous complex cellular and molecular pathways. Unbalance or failure of these
      pathways can lead to adverse remodelling of the heart and poor prognosis. Current
      clinical cardiac imaging modalities assess anatomy, perfusion, function, and
      viability of the myocardium, yet do not offer any insight into the specific
      molecular pathways involved in the repair process. Novel imaging techniques allow
      visualisation of these molecular processes and may have significant diagnostic
      and prognostic values, which could aid clinical management. Single photon
      emission tomography, positron-emission tomography, and magnetic resonance imaging
      are used to visualise various aspects of these molecular processes. Imaging
      probes are usually attached to radioisotopes or paramagnetic nanoparticles to
      specifically target biological processes such as: apoptosis, necrosis,
      inflammation, angiogenesis, and scar formation. Although the results from
      preclinical studies are promising, translating this work to a clinical
      environment in a valuable and cost-effective way is extremely challenging.
      Extensive evaluation evidence of diagnostic and prognostic values in multi-centre
      clinical trials is still required.

PMID- 29344830
TI  - RAP2.6L and jasmonic acid-responsive genes are expressed upon Arabidopsis
      hypocotyl grafting but are not needed for cell proliferation related to healing.
AB  - KEY MESSAGE: Jasmonic acid and RAP2.6L are induced upon wounding but are not
      involved in cell proliferation during healing in Arabidopsis hypocotyls. Plants
      produce jasmonic acid in response to wounding, but its role in healing, if any,
      has not been determined. Previously, the jasmonic acid-induced transcription
      factor, RAP2.6L, related to APETALA 2.6-like, was identified as a spatially
      expressed factor involved in tissue reunion in partially incised flowering stems
      of Arabidopsis. In the present study, we investigated the function of JA and
      RAP2.6L on wound healing using an Arabidopsis hypocotyl-grafting system, in which
      separated tissues are reattached by vascular tissue cell proliferation. The
      jasmonic acid-responsive genes AOS and JAZ10 were transiently expressed
      immediately after grafting. We confirmed that the endogenous content of jasmonic
      acid-Ile, which is the bioactive form of jasmonic acid, increased in hypocotyls 1
      h after grafting. Morphological analysis of the grafted tissue revealed that
      vascular tissue cell proliferation occurred in a similar manner in wild-type
      Arabidopsis, the jasmonic acid-deficient mutant aos, the jasmonic acid
      insensitive mutant coi1, and in Arabidopsis that had been exogenously treated
      with jasmonic acid. RAP2.6L expression was also induced during graft healing.
      Because RAP2.6L expression occurred during graft healing in aos and coi1, its
      expression must be regulated via a jasmonic acid-independent pathway. The rap2.6L
      mutant and dominant repressor transformants for RAP2.6L showed normal cell
      proliferation during graft healing. Taken together, our results suggest that JA
      and RAP2.6L, induced by grafting, are not necessary for cell proliferation
      process in healing.

PMID- 29344833
TI  - Violence Against Women in Cambodia: Towards a Culturally Responsive Theory of
      Change.
AB  - Almost one in four women in Cambodia is a victim of physical, emotional or sexual
      violence. This article brings together two seldom connected fields: Theory of
      Change (ToC) and cultural responsiveness in international development. It applies
      these approaches to a priority in global health, which is to prevent violence
      against women (VAW) and, drawing on my research on the epigenesis of VAW in
      Cambodia, develops an argument on the need for interventions to work with
      tradition and culture rather than only highlight it in problematic terms. The
      research draws on an ethnographic study carried out in Cambodia with 102
      perpetrators and survivors of emotional, physical and sexual VAW and 228 key
      informants from the Buddhist and healing sectors. The eight 'cultural attractors'
      identified in the author's prior research highlight the cultural barriers to
      acceptance of the current Theory of Change. ToC for VAW prevention in Cambodia
      seems to assume that local culture promotes VAW and that men and women must be
      educated to eradicate the traditional gender norms. There is a need for
      interventions to work with tradition and culture rather than only highlight it in
      problematic terms. The cultural epigenesis of VAW in Cambodia is an insight which
      can be used to build culturally responsive interventions and strengthen the
      primary prevention of VAW.

PMID- 29344832
TI  - Mitogen activated protein kinase 6 and MAP kinase phosphatase 1 are involved in
      the response of Arabidopsis roots to L-glutamate.
AB  - KEY MESSAGE: The function and components of L-glutamate signaling pathways in
      plants have just begun to be elucidated. Here, using a combination of genetic and
      biochemical strategies, we demonstrated that a MAPK module is involved in the
      control of root developmental responses to this amino acid. Root system
      architecture plays an essential role in plant adaptation to biotic and abiotic
      factors via adjusting signal transduction and gene expression. L-Glutamate (L
      Glu), an amino acid with neurotransmitter functions in animals, inhibits root
      growth, but the underlying genetic mechanisms are poorly understood. Through a
      combination of genetic analysis, in-gel kinase assays, detailed cell elongation
      and division measurements and confocal analysis of expression of auxin, quiescent
      center and stem cell niche related genes, the critical roles of L-Glu in primary
      root growth acting through the mitogen-activated protein kinase 6 (MPK6) and the
      dual specificity serine-threonine-tyrosine phosphatase MKP1 could be revealed. In
      gel phosphorylation assays revealed a rapid and dose-dependent induction of MPK6
      and MPK3 activities in wild-type Arabidopsis seedlings in response to L-Glu.
      Mutations in MPK6 or MKP1 reduced or increased root cell division and elongation
      in response to L-Glu, possibly modulating auxin transport and/or response, but in
      a PLETHORA1 and 2 independent manner. Our data highlight MPK6 and MKP1 as
      components of an L-Glu pathway linking the auxin response, and cell division for
      primary root growth.

PMID- 29344831
TI  - Interaction network of core ABA signaling components in maize.
AB  - KEY MESSAGE: We defined a comprehensive core ABA signaling network in monocot
      maize, including the gene expression, subcellular localization and interaction
      network of ZmPYLs, ZmPP2Cs, ZmSnRK2s and the putative substrates. The
      phytohormone abscisic acid (ABA) plays an important role in plant developmental
      processes and abiotic stress responses. In Arabidopsis, ABA is sensed by the PYL
      ABA receptors, which leads to binding of the PP2C protein phosphatase and
      activation of the SnRK2 protein kinases. These components functioning diversely
      and redundantly in ABA signaling are little known in maize. Using Arabidopsis
      pyl112458 and snrk2.2/3/6 mutants, we identified several ABA-responsive ZmPYLs
      and ZmSnRK2s, and also ZmPP2Cs. We showed the gene expression, subcellular
      localization and interaction network of ZmPYLs, ZmPP2Cs, and ZmSnRK2s, and the
      isolation of putative ZmSnRK2 substrates by mass spectrometry in monocot maize.
      We found that the ABA dependency of PYL-PP2C interactions is contingent on the
      identity of the PP2Cs. Among 238 candidate substrates for ABA-activated protein
      kinases, 69 are putative ZmSnRK2 substrates. Besides homologs of previously
      reported putative AtSnRK2 substrates, 23 phosphoproteins have not been discovered
      in the dicot Arabidopsis. Thus, we have defined a comprehensive core ABA
      signaling network in monocot maize and shed new light on ABA signaling.

PMID- 29344834
TI  - Employment Rates in Flexible Assertive Community Treatment Teams in The
      Netherlands: An Observational Study.
AB  - We determined the proportions of clients treated in Flexible Assertive Community
      Treatment teams who were unemployed and gained employment and who were employed
      and lost employment. Secondly, we explored the demographical and clinical factors
      associated with employment. Data were collected during routine outcome
      monitoring. We calculated differences in employment rates over a year and
      explored differences in demographic characteristics at baseline between patient
      groups. Logistic regression analysis was used to estimate the role of clinical
      predictor variables on employment status. Over time, 10% remained employed, 5%
      lost their employment, 3% gained employment and 82% remained unemployed. Clients
      who found employment were younger, more often male, and had significantly fewer
      psychosocial problems and a higher subjective quality of life during follow-up
      than those who remained unemployed. Problems with motivation for treatment at
      baseline were related to losing employment or remaining unemployed. Better
      implementation of vocational services is very important for increasing the number
      of clients gaining employment.

PMID- 29344835
TI  - Genetic Evidence for the Role of a Rice Vacuolar Invertase as a Molecular Sink
      Strength Determinant.
AB  - BACKGROUND: Rice is a major crop feeding the majority of the global population,
      and increasing its sink strength is one of the modes to alleviate the declining
      availability of food for the rapidly growing world population. We demonstrate a
      role for an important rice vacuolar invertase isoform, OsINV3, in sink strength
      determination. RESULTS: OsINV3 mutants showed shorter panicles with lighter and
      smaller grains, owing to a smaller cell size on the outer and inner surfaces of
      the palea and lemma as observed by scanning electron microscopy. Further, strong
      promoter::GUS expression was observed in the palea, lemma and the rachis branches
      in the young elongating panicles, which supported the role of OsINV3 in cell
      expansion and thus, in spikelet size and panicle length determination. Size of
      the spikelet was found to directly influence the grain weight, which was
      confirmed by the lack of differences in weights of hulled grain for differently
      segregated alleles in the heterozygous lines. Assessment of field grown mutants
      not only revealed a drastic reduction in the percentage of ripened grain, 1000
      grain weight and final yield, but also significantly reduced partitioning of
      assimilates to the panicles, whereby the total dry weight remained unaffected.
      Determination of the non-structural carbohydrate contents revealed a lower hexose
      to-sucrose ratio in the panicles of the mutants from panicle initiation to 10
      days after heading, a stage that identifies as the critical pre-storage phase of
      grain filling, whereas the starch contents were not affected. In addition, strong
      promoter::GUS expression was observed in the dorsal end of ovary during the pre
      storage phase until 6 days after flowering, highlighting a function for OsINV3 in
      monitoring the initial grain filling stage. CONCLUSIONS: OsINV3 was found to
      regulate spikelet size by playing a key role in cell expansion, driving the
      movement of assimilates for grain filling by modulating the hexose-to-sucrose
      ratio, contributing in grain weight determination and thus, the grain yield.

PMID- 29344836
TI  - Boost Irradiation Integrated to Whole Brain Radiotherapy in the Management of
      Brain Metastases.
AB  - Our retrospective analysis aimed to evaluate the clinical value of dose
      intensification schemes: WBRT and consecutive, delayed, or simultaneous
      integrated boost (SIB) in brain metastasis (BM) management. Clinical data and
      overall survival (OS) of 468 patients with BM from various primaries treated with
      10 * 3 Gy WBRT (n = 195), WBRT+ 10 * 2 Gy boost (n = 125), or simultaneously 15 *
      2.2 Gy WBRT+0.7 Gy boost (n = 148) during a 6-year period were statistically
      analysed. Significant difference in OS could be detected with additional boost to
      WBRT (3.3 versus 6.5 months) and this difference was confirmed for BMs of lung
      cancer and melanoma and both for oligo- and multiplex lesions. The OS was
      prolonged for the RPA 2 and RPA3 categories, if patients received escalated dose,
      4.0 vs. 7.7 months; (p = 0.002) in class RPA2 and 2.6 vs. 4.2 months; (p <
      0.0001) in the class RPA 3 respectively. The significant difference in OS was
      also achieved with SIB. The shortened overall treatment time of SIB with lower
      WBRT fraction dose exhibited survival benefit over WBRT alone, and could be
      applied for patients developing BM even with unfavourable prognostic factors.
      These results warrant for further study of this approach with dose escalation
      using the lately available solutions for hippocampus sparing and fractionated
      stereotactic irradiation. The simultaneous delivery of WBRT with reduced fraction
      dose and boost proved to be advantageous prolonging the OS with shortened
      treatment time and reduced probability for cognitive decline development even for
      patients with poor performance status and progressing extracranial disease.

PMID- 29344837
TI  - Evaluation of the Profile and Mechanism of Neurotoxicity of Water-Soluble
      [Cu(P)4]PF6 and [Au(P)4]PF6 (P = thp or PTA) Anticancer Complexes.
AB  - [Cu(thp)4]PF6, [Cu(PTA)4]PF6, [Au(thp)4]PF6 and [Au(PTA)4]PF6 are phosphane (thp
      = tris(hydroxymethyl)phosphane; PTA = 1,3,5-triaza-7-phosphaadamantane) copper(I)
      and gold(I) water-soluble complexes characterized by high anticancer activity in
      a wide range of solid tumors, often able to overcome drug resistance of platinum
      based compounds. For these reasons, they have been proposed as a valid
      alternative to platinum-based chemotherapeutic drugs (e.g., cisplatin and
      oxaliplatin). In vitro experiments performed on organotypic cultures of dorsal
      root ganglia (DRG) from 15-day-old rat embryos revealed that copper-based
      compounds were not neurotoxic even at concentrations higher than the IC50
      obtained in human cancer cells while [Au(PTA)4]PF6 was neurotoxic at lower
      concentration than IC50 in cancer cell lines. The ability of these compounds to
      hinder the proteasome machinery in DRG neurons was tested by fluorimetric assay
      showing that the non-neurotoxic copper-based complexes do not inhibit proteasome
      activity in DRG primary neuron cultures. On the contrary, the neurotoxic complex
      [Au(PTA)4]PF6, induced a significant inhibition of proteasome activity even at
      concentrations lower than the IC50 in cancer cells. The proteasome inhibition
      induced by [Au(PTA)4]PF6 was associated with a significant increase in alpha
      tubulin polymerization that was not observed following the treatment with copper
      based compounds. Uptake experiments performed by atomic absorption spectrometry
      showed that both copper-based complexes and [Au(PTA)4]PF6 are internalized in
      neuron cultures. In vitro and in vivo preliminary data confirmed copper-based
      complexes as the most promising compounds, not only for their anticancer activity
      but also concerning the peripheral neurotoxicity profile.

PMID- 29344838
TI  - Association between human brucellosis and adverse pregnancy outcome: a cross
      sectional population-based study.
AB  - To investigate the association between the incidence of human brucellosis (HB)
      and adverse pregnancy outcomes (APOs), a population-based, cross-sectional
      aggregate data study was conducted in Israel between 2010 and 2014. HB-endemic
      localities were matched by ethnicity, population size and socioeconomic status to
      localities with a low incidence of HB. We compared APO rates in high-incidence vs
      low-incidence localities. The primary outcome was intrauterine fetal demise
      (IUFD). Secondary outcomes were premature birth (less than 37 weeks), early or
      threatened labour and poor fetal growth. APOs are expressed as events per 1,000
      live or dead births. Eleven high-incidence localities, all Arab villages or
      cities, were matched to 11 low-incidence localities. Localities were well-matched
      with regard to the matching criteria, fertility indices, health insurance access
      and education, but were imbalanced geographically. All defined APOs occurred
      significantly more frequently in the high-incidence localities. The associations
      translated to an absolute increase of 3.6 cases of IUFD (95% CI 1.6-5.3), 11.7
      preterm births (4.8-18.3), 6.6 cases of early or threatened labour (2.2-10.9) and
      7 cases of poor fetal growth (3-10.8), per 10,000 live or dead births. Owing to a
      geographic imbalance between high- and low-incidence localities, we conducted an
      analysis restricted to Southern localities of Arab Bedouins showing a significant
      association between yearly HB incidence and IUFD incidence, odds ratio 1.05 (1.03
      1.06). HB incidence is epidemiologically linked to serious pregnancy
      complications. Early detection of infection through active surveillance during
      pregnancy followed by appropriate treatment should be evaluated as additional
      public heath strategy in endemic settings.

PMID- 29344839
TI  - Risk factors of venous thrombo-embolism during cytomegalovirus infection in
      immunocompetent individuals. A systematic review.
AB  - Most of the effects and complications of cytomegalovirus (CMV) infection are
      still unknown, even though its tropism for the endothelium has been extensively
      investigated. In fact, CMV is suspected to be a cause of venous thrombo-embolism
      (VTE) since 1974, but there is still no consensus about the management of CMV
      related thrombosis and how to prevent it. Cytomegalovirus-related thrombosis has
      been reported mostly in immunocompromised patients, rarely in immunocompetent
      individuals. In order to identify potential risk factors of CMV-related
      thrombosis, we performed a systematic review of the literature regarding
      immunocompetent patients with cytomegalovirus infection and thrombosis. We found
      115 cases with a mean age of 37.36 years (SD +/- 16.43 years). Almost half the
      female patients were assuming EP contraception at the time of the event, and
      almost half the patients were affected by a coagulation disorder. Interestingly,
      just two women and four men had no risk factor for thrombosis other than the CMV
      infection at the time of the event. In conclusion, coagulation disorders and EP
      contraception have to be taken into a great deal of consideration in patients
      with CMV infection, since they could be important risk factors for VTE. Knowing
      the correlation with coagulation disorders, the use of anticoagulation drugs
      cannot be considered overtreatment. It was not feasible to determine the
      usefulness of an antiviral treatment. Further studies, even randomized ones, are
      required to determine the usefulness of antiviral drugs and the real prevalence
      of CMV-related VTE.

PMID- 29344840
TI  - Design and Rationale for comParison Between ticagreLor and clopidogrEl on
      mIcrocirculation in Patients with Acute cOronary Syndrome Undergoing Percutaneous
      Coronary Intervention (PLEIO) Trial.
AB  - It has been previously demonstrated that ticagrelor can reduce mortality compared
      to clopidogrel in acute coronary syndrome (ACS) patients. However, the mechanism
      for this mortality reduction remains uncertain. The objective of the present
      study is to assess the impact of chronic ticagrelor treatment on microvascular
      circulation. A total of 120 participants aged 20-85 years with clinical diagnosis
      of ACS will be randomized in a 1:1 fashion to the following two groups:
      ticagrelor 90 mg twice daily; clopidogrel 75 mg once daily. To evaluate the
      status of microcirculation, the primary end point is coronary microvascular
      dysfunction measured using an index of microcirculatory resistance (IMR) at 6
      months after receiving the study agent. The purpose of this trial is to
      investigate whether ticagrelor, beyond its antiplatelet efficacy, could improve
      coronary microcirculation more effectively than clopidogrel for patients with
      ACS.

PMID- 29344841
TI  - Association of D-dimer with Plaque Characteristics and Plasma Biomarkers of
      Oxidation-Specific Epitopes in Stable Subjects with Coronary Artery Disease.
AB  - D-dimer has emerged as a biomarker of cardiovascular event risk, yet
      pathophysiological factors associated with plasma D-dimer levels in stable
      coronary artery disease (CAD) subjects are poorly understood. In 106 stable CAD
      subjects undergoing intravascular ultrasound with virtual histology (IVUS-VH), we
      measured D-dimer, lipoprotein(a) (Lp(a)), plasminogen, biomarkers reflecting
      oxidation-specific epitopes (OSE) such as oxidized phospholipids on
      apolipoprotein B-100 (OxPL-apoB), OxPL on plasminogen (OxPL-PLG), and
      autoantibodies to phosphorylcholine-BSA [PC-BSA] and a malondialdehyde [MDA]
      mimotope. In univariate analysis, D-dimer was positively associated with Lp(a),
      OxPL-apoB, OxPL-PLG, and coronary artery calcium, and inversely associated with
      autoantibodies to OSE and plaque fibrosis. D-dimer levels > 500 ng/ml also showed
      positive association with plaque necrosis. After multivariate analysis, D-dimer
      remained significantly associated with Lp(a) and plaque calcium. While further
      studies are needed, results provide evidence that plasma D-dimer levels are
      associated with levels of OxPLs and IVUS-VH indices linked to plaque erosion and
      rupture.

PMID- 29344842
TI  - Reasons for Abortion: Religion, Religiosity/Spirituality and Attitudes of Male
      Secondary School Youth in South Africa.
AB  - This study focused on the relationship between religion, religiosity/spirituality
      (R/S), and attitudes of a sample of South African male secondary school youth
      toward women's rights to legal abortion in different situations. We distributed
      400 self-administered questionnaires assessing the main variables (attitudes
      toward reasons for abortion and R/S) to the target sample in six different
      secondary schools in KwaZulu-Natal, South Africa. The responses of a final sample
      of 327 learners were then analyzed using the Statistical Package for the Social
      Sciences (SPSS) software. The findings revealed that religion and R/S play a role
      in the youths' attitudes toward abortion. While the Hindu subsample indicated
      higher overall support across the different scenarios, the Muslim subsample
      reported greater disapproval than the other groups on 'Elective reasons' and in
      instances of 'Objection by significant others.' The Christian youth had the most
      negative attitudes to abortion for 'Traumatic reasons' and 'When women's
      health/life' was threatened. Across the sample, higher R/S levels were linked
      with more negative attitudes toward reasons for abortion.

PMID- 29344843
TI  - Hepatocellular Carcinoma Spreading Through the Round Ligament.

PMID- 29344844
TI  - Response to: "The Role of Bundle Size for Preventing Surgical Site Infections
      after Colorectal Surgery: Is More Better?"

PMID- 29344845
TI  - Two Cases of Dermatophytic Granuloma Successfully Treated with Terbinafine.
AB  - Dermatophytic granuloma, also called Majocchi's granuloma (MG), is an uncommon
      infection of the dermis and subcutaneous tissues that can occur in both healthy
      and immunosuppressed hosts. We present two cases of MG with different clinical
      features. Both patients had satisfactory relief after treatment with terbinafine.

PMID- 29344846
TI  - Evaluation of psychosocial and biological parameters in women seeking for a
      caesarean section and women who are aiming for vaginal delivery: a cross
      sectional study.
AB  - PURPOSE: To investigate psychosocial and biological parameters that may influence
      decision-making concerning the mode of delivery in women with caesarean section
      on maternal request (CSMR). METHODS: Two hundred and two women were enrolled
      prospectively. The study sample (n = 93) consisted of women who aimed for CSMR,
      the control sample were women who seeked for vaginal delivery (n = 109).
      Parturients of both samples were enrolled during the pre-birth counselling at the
      delivery room at the University Medical Centre Mannheim, University Heidelberg,
      Germany. Women completed standardised questionnaires regarding psychosocial
      burden (SCL-R 90), fear of childbirth (W-DEQ) and anxiety (STAI), personality
      structure (HEXACO-Pi-R), and ambiguity tolerance (PFI, PNS, and NFC), social
      support (F-SozU) as well as one questionnaire assessing demographic parameters
      and further factors potentially influencing their choice of the mode of delivery.
      Hair cortisol concentration as a marker for chronic psychological stress and
      pressure pain threshold with a pressure algometer was assessed. RESULTS: Women in
      the CSMR sample had less social support (F-SozU: 2.99 +/- 0.52 vs. 3.12 +/- 0.32;
      p = 0.043) and were less educated (high school or university degree: 37 vs. 71%,
      p = 0.001) compared to parturients of the control sample. Women who underwent
      CSMR were less open-minded (HEXACO-Pi-R: 3.08 +/- 0.57 vs. 3.26 +/- 0.50; p =
      0.016) and less extroverted (HEXACO-Pi-R: 3.34 +/- 0.36 vs. 3.46 +/- 0.41; p =
      0.041). The control collective showed higher scores in negative appraisal of the
      birth ('W-DEQ-negative appraisal': 2.5 +/- 0.8 vs. 2.2 +/- 0.9; p = 0.006),
      whereas "lack of positive anticipation" was higher in the study collective ('W
      DEQ-lack of positive anticipation': 3.2 +/- 1.2 vs. 2.8 +/- 0.8; p = 0.015). The
      study collective had higher pressure pain threshold values (5.07 +/- 2.06 vs.
      4.35 +/- 1.38; p = 0.007), while no significant differences were observed in hair
      cortisol concentration comparing both groups (5.0 +/- 11.4 vs. 4.9 +/- 8.3; p =
      0.426). The majority of the control collective (80%) had chosen the vaginal route
      as their mode of delivery before pregnancy, whereas only 21% of the women in the
      study collective decided to undergo CSMR before conception. The advice of social
      sources including both medical and non-medical aspects was rated less important
      in the study sample, with significant differences indicating a lower relevance of
      counsel from friends (p = 0.002) and midwives (p < 0.001). CONCLUSION: Women who
      inquired a CSMR had lower social support, were less educated, more anxious, and
      had a lower sensitivity for physical pain compared to women seeking for
      spontaneous delivery. This should be considered when counselling women requiring
      CSMR and could be leverage points to intervene to reduce the continuously
      increasing CSMR rate.

PMID- 29344848
TI  - Current status and future possibilities of molecular genetics techniques in
      Brassica napus.
AB  - As PCR methods have improved over the last 15 years, there has been an upsurge in
      the number of new DNA marker tools, which has allowed the generation of high
      density molecular maps for all the key Brassica crop types. Biotechnology and
      molecular plant breeding have emerged as a significant tool for molecular
      understanding that led to a significant crop improvement in the Brassica napus
      species. Brassica napus possess a very complicated polyploidy-based genomics. The
      quantitative trait locus (QTL) is not sufficient to develop effective markers for
      trait introgression. In the coming years, the molecular marker techniques will be
      more effective to determine the whole genome impairing desired traits. Available
      genetic markers using the single-nucleotide sequence (SNP) technique and high
      throughput sequencing are effective in determining the maps and genome
      polymorphisms amongst candidate genes and allele interactions. High-throughput
      sequencing and gene mapping techniques are involved in discovering new alleles
      and gene pairs, serving as a bridge between the gene map and genome evaluation.
      The decreasing cost for DNA sequencing will help in discovering full genome
      sequences with less resources and time. This review describes (1) the current use
      of integrated approaches, such as molecular marker technologies, to determine
      genome arrangements and interspecific outcomes combined with cost-effective
      genomes to increase the efficiency in prognostic breeding efforts. (2) It also
      focused on functional genomics, proteomics and field-based breeding practices to
      achieve insight into the genetics underlying both simple and complex traits in
      canola.

PMID- 29344847
TI  - The effect of surgical management of endometrioma on the IVF/ICSI outcomes when
      compared with no treatment? A systematic review and meta-analysis.
AB  - OBJECTIVE: To assess the impact of surgical management of endometrioma on the
      outcome of assisted reproduction treatment (ART). DESIGN: A systematic review and
      meta-analysis. SETTING: Department of reproductive medicine at teaching
      university hospital, UK. PATIENTS: Subfertile women with endometrioma undergoing
      ART. INTERVENTIONS: Surgical removal of endometrioma or expectant management.
      MAIN OUTCOME MEASURES: Clinical pregnancy rate, pregnancy rate, live birth rate,
      number of oocytes retrieved and number of embryos available and ovarian response
      to gonadotrophins. RESULTS: An extensive search of electronic databases for
      articles published from inception to September 2016 yielded 11 eligible studies
      for meta-analysis. Meta-analysis was conducted comparing surgery versus no
      treatment of endometrioma. There were no significant differences in pregnancy
      rate per cycle, clinical pregnancy rate and live birth rate between women who
      underwent surgery for endometrioma and those who did not. CONCLUSION: Current
      evidence suggests that women with endometriosis-related infertility have similar
      cycle outcomes to other patients going through ART. It is pertinent for
      clinicians to assess the risks of surgical intervention on ovarian reserve prior
      to initiating therapy.

PMID- 29344849
TI  - A simple protocol for transfecting human mesenchymal stem cells.
AB  - OBJECTIVES AND RESULTS: Mesenchymal stromal cells (MSCs) are potential targets
      for cell and gene therapy-based approaches against a variety of different
      diseases. The MSCs from bone marrow are a promising target population as they are
      capable of differentiating along multiple lineages and have significant expansion
      capability. These characteristics make them strong candidates for delivering
      genes and restoring organ systems function. However, as other primary cells, MSCs
      are difficult to transfect. In order to standardize a simple protocol for
      transfection of MSCs, we conducted a series of experiments and achieved a
      protocol that does not require the use of viral particles or specific expensive
      equipment. CONCLUSION: MSCs transfection at early passages using a ratio
      lipid/DNA of 3.0 uL/ug with Lipofectamine 3000(r) yields good transfection
      efficiencies for human MSCs (up to 26%) and is rapid, simple, and safe.

PMID- 29344850
TI  - HuR facilitates cancer stemness of lung cancer cells via regulating miR-873/CDK3
      and miR-125a-3p/CDK3 axis.
AB  - OBJECTIVES: To study the roles and mechanisms of HuR in cancer stem cell
      maintenance of lung cancer. RESULTS: HuR expression was increased in tumor
      spheres of lung cancer cells. Knockdown of HuR suppressed spheroid formation and
      size, inhibited the expression of stemness-related marker, Oct4, Nanog and ALDH
      in lung cancer cells. Importantly, HuR and CDK3 expressions were increased in
      lung cancer tissues compared with normal adjacent tissues, and positively
      correlated. Mechanistically, HuR directly bound to CDK3, and increased CDK3 mRNA
      stability and expression. Additionally, miR-873 or miR-125a-3p attenuated the
      promotion of HuR on CDK3 expression and lung cancer stemness. Furthermore, HuR
      facilitated lung cancer stemness dependent on CDK3 expression. miR-873 or miR
      125a-3p level was negatively correlated with HuR and CDK3 expression levels in
      lung cancer tissues. CONCLUSIONS: HuR facilitates lung cancer stemness via
      regulating miR-873/CDK3 and miR-125a-3p/CDK3 axis.

PMID- 29344851
TI  - The evolution of CRISPR/Cas9 and their cousins: hope or hype?
AB  - Clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system
      allows biologists to edit genomic DNA of any cell in precise and specific way,
      entailing great potential for crop improvement, drug development and gene
      therapy. The system involves a nuclease (Cas9) and a designed guide RNA that are
      involved in wide range of applications such as genome modification,
      transcriptional modulation, genomic loci marking and RNA tracking. The limitation
      of the technique, in view of resistance of thymidine-rich genome to Cas9
      cleavage, has now been overcome by the use of Cpf1 nuclease. In this review, we
      present an overview of CRISPR nucleases (Cas9 or Cpf1) with particular emphasis
      on human genome modification and compare their advantages and limitations.
      Furthermore, we summarize some of the pros and cons of CRISPR technology
      particularly in human therapeutics.

PMID- 29344852
TI  - Laser Capture Microdissection: Insights into Methods and Applications.
AB  - Laser capture microdissection is a non-molecular, minimally disruptive method to
      obtain cytologically and/or phenotypically defined cells or groups of cells from
      heterogeneous tissues. Its advantages include efficient rapid and precise
      procurement of cells. The potential disadvantages include time consuming,
      expensive, and limited by the need for a pathologist for recognition of distinct
      subpopulations within a specified sample. Overall it is versatile allowing the
      preparation of homogenous isolates of specific subpopulations of cells from which
      DNA/RNA or protein can be extracted for RT-PCR, quantitative PCR, next-generation
      sequencing, immunoblot blot analyses, and mass spectrometry.

PMID- 29344853
TI  - Laser Microdissection-Based Microproteomics of Formalin-Fixed and Paraffin
      Embedded (FFPE) Tissues.
AB  - Laser microdissection-based proteomics on formalin-fixed and paraffin-embedded
      tissues is usually performed from relatively large tissue areas or pools of
      multiple tissue pieces. However, several molecular pathology studies require
      working on very limited amounts of tissue. This is for example the case when very
      early cancer lesions have to be handled. Hereby, we present a method for the
      processing of very small pieces of formalin-fixed and paraffin-embedded tissues
      for proteomic purposes. This approach is designed in order to avoid sample loss
      during technical processing and to optimize the digestion of tissue areas
      containing as little as 2700 cells.

PMID- 29344854
TI  - Laser Microdissection Workflow for Isolating Nucleic Acids from Fixed and Frozen
      Tissue Samples.
AB  - Laser Capture Microdissection has earned a permanent place among modern
      techniques connecting histology and molecular biology. Laser Capture
      Microdissection has become an invaluable tool in medical research as a means for
      collection of specific cell populations isolated from their environment. Such
      genomic sample enrichment dramatically increases the sensitivity and precision of
      downstream molecular assays used for biomarker discovery, monitoring disease
      onset and progression, and in the development of personalized medicine. The
      diversity of research targets (cancerous and precancerous lesions in clinical and
      animal research, cell pellets, rodent embryos, frozen tissues, archival
      repository slides, etc.) and scientific objectives present a challenge in
      establishing standard protocols for Laser Capture Microdissection. In the present
      chapter, we share our experiences in design and successful execution of numerous
      diverse microdissection projects, and provide considerations to be taken into
      account in planning a microdissection study. Our workflow and protocols are
      standardized for a wide range of animal and human tissues and adapted to
      downstream analysis platforms.

PMID- 29344855
TI  - Protocol for the Analysis of Laser Capture Microdissected Fresh-Frozen Tissue
      Homogenates by Silver-Stained 1D SDS-PAGE.
AB  - The heterogeneity present in solid tumors adds significant difficulty to
      scientific analysis and improved understanding. Fundamentally, solid tumor
      formation consists of cancer cells proper along with stromal elements. The
      burgeoning malignant process is dependent upon modified stromal elements.
      Collectively, the stroma forms an essential microenvironment, which is
      indispensable for the survival and growth of the malignant neoplasm. This
      cellular heterogeneity makes molecular profiling of solid tumors via mass
      spectrometry (MS)-based proteomics a daunting task. Laser capture microdissection
      (LCM) is commonly used to obtain distinct histological cell types (e.g., tumor
      parenchymal cells, stromal cells) from tumor tissue and attempt to address the
      tumor heterogeneity interference with downstream liquid chromatography (LC) MS
      analysis. To provide optimal LC-MS analysis of micro-scale and/or nano-scale
      tissue sections, we modified and optimized a silver-stained one-dimensional
      sodium dodecyl sulfate polyacrylamide gel electrophoresis (1D-SDS-PAGE) protocol
      for the LC-MS analysis of LCM-procured fresh-frozen tissue specimens. Presented
      is a detailed in-gel digestion protocol adjusted specifically to maximize the
      proteome coverage of amount-limited LCM samples, and facilitate in-depth
      molecular profiling. Following LCM, targeted tissue sections are further
      fractionated using silver-stained 1D-SDS-PAGE to resolve and visualize tissue
      proteins prior to in-gel digestion and subsequent LC-MS analysis.

PMID- 29344856
TI  - Next-Generation Sequencing Analysis of Laser-Microdissected Formalin-Fixed and
      Paraffin-Embedded (FFPE) Tissue Specimens.
AB  - In recent years, next-generation sequencing (NGS) became widely used in molecular
      pathology. Comprehensive mutational profiling improved diagnosis and prognosis,
      as well as the identification of therapeutically relevant genetic alterations.
      However, the vast majority of studies analyzing tissue samples use DNA extracted
      from bulk tissue or only manually microdissected specimens. Laser-assisted
      microdissection offers the possibility of isolating morphologically defined small
      tissue compartments (like individual glands) or even of single cells for further
      molecular analysis. Even formalin-fixed paraffin-embedded (FFPE) tissue specimens
      can be used for laser-assisted microdissection. Combining these two innovative
      powerful methodological approaches provides invaluable insights into the genetic
      profile of any cell type and tissue compartment of interest, contributing to a
      better understanding of fundamental biological processes and disease-specific
      mechanisms.In this chapter, a detailed protocol is provided for microdissection
      of human mammary adenomyoepithelioma tissue specimens and subsequent targeted
      resequencing of a panel of cancer-related genes using IonTorrent/PGM technology.

PMID- 29344857
TI  - Adaptation of Laser Microdissection Technique to Nanostring RNA Analysis in the
      Study of a Spontaneous Metastatic Mammary Carcinoma Mouse Model.
AB  - The mouse model characterized by spontaneous lung metastasis from JygMC (A) cells
      closely resembles the human triple negative breast cancer (TNBC) subtype. The
      primary tumors morphologically present both epithelial and spindle-like cells,
      but metastases in lung parenchyma display only adenocarcinoma properties. In the
      study of molecular signatures, laser capture microdissection (LCM) on frozen
      tissue sections was used to separate the following regions of interest: the
      epithelial-mesenchymal transition (EMT), mesenchymal-epithelial transition (MET),
      carcinoma, lung metastases, normal mammary gland and normal lung parenchyma.
      NanoString was selected for the study of molecular signatures in LCM targets as a
      reliable downstream gene expression platform allowing analysis of tissue lysates
      without RNA extraction and amplification. This chapter provides detailed
      protocols for the collection of tissue, LCM sample preparation and dissection,
      production of lysates, extraction, and quality control of RNA for NanoString
      analysis, as well as the methodology of Nanostring gene expression profiling
      experiment.

PMID- 29344858
TI  - Laser Capture Microdissection as a Tool to Study the Mucosal Immune Response in
      Celiac Disease.
AB  - Laser capture microdissection (LCM) is a powerful tool for selection and
      isolation of single cells or compartments from complex primary tissues to perform
      molecular analyses. Celiac disease is a genetic autoimmune disorder where the
      ingestion of gluten leads to damage in the small intestine. Increased
      intraepithelial lymphocytes and the presence of the lamina propria inflammatory
      infiltrate of the duodenal mucosa is a common part of the disease. These cells
      promote inflammatory processes through the release of cytokines. Here, we
      describe the use of LCM and real-time quantitative PCR (RT-qPCR) to analyze
      cytokine profile information in distinct duodenal mucosa tissue compartments of
      celiac patients.

PMID- 29344859
TI  - Laser Capture Microdissection and Isolation of High-Quality RNA from Frozen
      Endometrial Tissue.
AB  - Laser capture microdissection (LCM) allows expression profiling of specific cell
      populations within tissues. However, isolation of high-quality RNA from laser
      capture microdissected frozen tissue is beset by problems arising from intrinsic
      tissue RNase activity. Herein, we describe an optimized staining/LCM/RNA
      extraction protocol developed for the isolation of epithelial RNA from frozen
      tissue sections using human endometrial cancer as a model tissue. This method
      combines excellent, reproducible visualization of tissue morphology with the
      isolation of high-integrity RNA suitable for downstream applications such as
      expression microarray analysis. We present quantitative and qualitative RNA data
      obtained from >200 endometrial epithelial samples (normal, hyperplastic, and
      cancerous), where 92% of samples had RIN values of 7 and above and highlight
      common pitfalls faced by investigators. This method should also be broadly
      applicable to a range of other tissue types.

PMID- 29344860
TI  - Laser Microdissection for Human Papillomavirus (HPV) Genotyping Attribution and
      Methylation Pattern Analyses of Squamous Intraepithelial Lesions.
AB  - Human papillomavirus (HPV) is a nearly ubiquitous infectious organism. It is
      estimated that 80% of sexually active adults will be exposed to anogenital HPVs
      in their lifetime, and detection of multiple genotypes in an anogenital sample is
      common. Detection and genotyping of HPV is usually performed by DNA testing, and
      less frequently by mRNA testing. HPV genotype testing and characterization of DNA
      methylation patterns of HPV-related lesions can provide important biological,
      epidemiological, and potentially relevant clinical information in individuals and
      populations. The use of laser capture microdissection to isolate cells within a
      specific lesion allows for very precise molecular characterization and hence
      causal attribution. This chapter describes detailed protocols for the capture of
      lesion-specific tissue from formalin-fixed, paraffin-embedded (FFPE) biopsy
      tissue, and downstream DNA testing for lesion-specific HPV genotype and their
      methylation patterns.

PMID- 29344861
TI  - Laser Capture Microdissection and Transcriptional Analysis of Sub-Populations of
      the Osteoblast Lineage from Undecalcified Bone.
AB  - Transcriptional analysis of tissue samples is a useful and widely applied
      approach to provide insight into the molecular mechanisms engaged in response to
      phenotypic changes or external stimuli. We describe a method that overcomes the
      technical challenges associated with the application of Laser Capture
      Microdissection to undecalcified bone enabling us to collect high-quality bone
      tissue with maintained cellular morphology that is suitable for cryosectioning,
      fixation, and cutting. Using this method, we obtain samples enriched for specific
      cell types from the mature osteoblast lineage (osteoblasts, lining cells, i.e.,
      quiescent osteoblasts, and osteocytes). RNA is well preserved and following
      extraction and amplification can be used as input to both low and high-throughput
      RNA analysis formats.

PMID- 29344862
TI  - Cell Type-Specific Laser Capture Microdissection for Gene Expression Profiling in
      the Human Brain.
AB  - Cell type-specific laser microdissection technologies in combination with
      molecular techniques to determine gene expression profiles have become powerful
      tools to gain insight into the neurobiological basis of neural circuit
      disturbances in various neurologic or psychiatric diseases. To identify specific
      cell populations in human postmortem brain tissue, one can use the inherent
      properties of the cells, such as pigmentation and morphology or their structural
      composition through immunohistochemistry (IHC). Here, we describe the isolation
      of homogeneous neurons and oligodendrocytes and the extraction of high-quality
      RNA from these cells in human postmortem brain using a combination of rapid IHC,
      Nissl staining, or simple morphology with Laser Capture Microdissection (LCM), or
      Laser Microdissection (LMD).

PMID- 29344863
TI  - The Isolation of Pure Populations of Neurons by Laser Capture Microdissection:
      Methods and Application in Neuroscience.
AB  - In mammals, the central nervous system (CNS) is constituted of various cellular
      elements, posing a challenge to isolating specific cell types to investigate
      their expression profile. As a result, tissue homogenization is not amenable to
      analyses of motor neurons profiling as these represent less than 10% of the total
      spinal cord cell population. One way to tackle the problem of tissue
      heterogeneity and obtain meaningful genomic, proteomic, and transcriptomic
      profiling is to use laser capture microdissection technology (LCM). In this
      chapter, we describe protocols for the capture of isolated populations of motor
      neurons from spinal cord tissue sections and for downstream transcriptomic
      analysis of motor neurons with RT-PCR. We have also included a protocol for the
      immunological confirmation that the captured neurons are indeed motor neurons.
      Although focused on spinal cord motor neurons, these protocols can be easily
      optimized for the isolation of any CNS neurons.

PMID- 29344864
TI  - Laser Capture Microdissection in Traumatic Brain Injury Research: Obtaining
      Hippocampal Subregions and Pools of Injured Neurons for Genomic Analyses.
AB  - The methods presented here are based on our laboratory's 15 years of experience
      using laser capture microdissection to obtain samples for the study of gene
      expression after traumatic brain injury (TBI) using a well-established rat model
      of experimental TBI. Here, we describe how to use the ArcturusXT laser capture
      microdissection system to capture swaths of specific regions of the rat
      hippocampus as well as specific neuronal populations defined by Fluoro-Jade C
      staining. Staining with Fluoro-Jade C identifies a neuron that is in the process
      of degeneration. We have optimized our protocols for Fluoro-Jade C tissue
      staining and laser capture microdissection to maintain RNA integrity which is
      essential for a variety of downstream applications, such as microarray, PCR
      array, and quantitative real-time PCR analyses.

PMID- 29344865
TI  - Isolation of Distinct Types of Neurons from Fresh Brain Tissue Using Laser
      Microdissection in Combination with High-Performance Liquid Chromatography-Mass
      Spectrometry.
AB  - Humans age and the ageing process affects cells in all areas of the human body,
      including nerve cells within the brain. With advancing age there is also a rise
      in the probability of developing a neurodegenerative disorder such as, e.g.,
      amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease, or
      Alzheimer's disease. In all these age-related neurodegenerative disorders,
      distinct neuron populations within specific brain regions are primarily affected.
      For example, Parkinson's disease is characterized by a slowly progressive
      degeneration of dopaminergic neurons in the substantia nigra whereas the
      entorhinal cortex is first affected in Alzheimer's disease. In patients suffering
      from Huntington's disease, neurons in both striatum and cortex undergo
      substantial cell loss and in amyotrophic lateral sclerosis the neurodegeneration
      arises from the spinal cord and the motor cortex. For the investigation of the
      differences in neuronal vulnerability, it is important to examine the protein
      expression pattern in these specific neural populations. By this, conclusions
      about the origination process of these diseases can be achieved. In order to
      obtain this objective, specific isolation of distinct neurons from the
      surrounding brain tissue is indispensable. However, discrimination as well as
      isolation of distinct types of neurons can be challenging, due to the brain
      tissue's complexity. With traditional methods such as the homogenization of
      tissue samples, a specific isolation of single neuron populations is not feasible
      because homogenization results into a mixture containing all cell types. Laser
      microdissection can overcome this technical limitation. First, this method
      enables visualization of tissues via a microscopic unit and therefore an enhanced
      discrimination of different brain cells. Second, a laser device guarantees a
      contact-free and consequently a contamination-free separation of distinct neurons
      from the surrounding brain tissue. In the following, we present a detailed
      protocol that includes a workflow for the isolation and analysis of neurons from
      freshly frozen post mortem human brain tissue samples. During this procedure, the
      brain tissue is sectioned, stained, laser microdissected, and ultimately analyzed
      by high-performance liquid chromatography-mass spectrometry.

PMID- 29344866
TI  - Immuno-Guided Laser-Capture Microdissection of Glial Cells for mRNA Analysis.
AB  - Laser-capture microdissection (LCM) allows for retrieval of specific cell
      populations in situ. By combining immunofluorescent labeling with LCM, mRNAs can
      be probed by qRT-PCR for determining in situ gene expression during health and
      disease. This approach permits obtaining and analyzing histologically enriched
      cell populations in a tissue that can be hardly obtained from other methods such
      as white matter astrocytes from rodents or any individual cell population from
      archival human or rodent brain tissues. Herein, we present our methodology of
      laser-captured mouse spinal cord white matter astrocytes, which can be adapted
      for any cell type in CNS tissue and low RNAse containing tissues. The methods
      presented with an emphasis on tips and advices include the cryostat section
      preparation from snap-frozen tissue, an adapted immunofluorescent labeling, a
      brief overview of LCM using a UV-based technology with polyethylene membrane
      glass slides, procedures for direct use of RNA from lysis buffer vs. column-based
      purified RNA, RNA quality/quantity assessment, the reverse transcription and
      preamplification steps used before real-time qPCR analysis.

PMID- 29344867
TI  - Immuno-Laser-Capture Microdissection for the Isolation of Enriched Glial
      Populations from Frozen Post-Mortem Human Brain.
AB  - Laser-capture microdissection (LCM) has revolutionized the isolation of defined
      regions and specific cell populations from human tissue. This approach used in
      combination with immunohistochemistry (immuno-LCM) has become a valuable method
      for isolating individual cell-types from a complex heterogeneous population.
      Here, we describe the detailed methodology required for the isolation of enriched
      populations of GFAP+ astrocytes, OSP+ oligodendrocytes, and CD68+ microglia from
      frozen post-mortem human central nervous system tissue using immuno-LCM.

PMID- 29344868
TI  - Laser-Capture Microdissection for the Analysis of Rat and Human Spinal Cord
      Ependyma by qPCR.
AB  - In the last few decades many efforts have been dedicated to decipher the nature
      and regenerative potential of neurogenic niches and endogenous stem cells after
      damage of the central nervous system. In the spinal cord, it has been largely
      focused on the ependymal region, which hosts neural precursors/stem cells (NSC)
      in rodents but differs between species and ages. In the current chapter, we
      detail our protocol to study the gene expression profile of this region using
      fresh frozen blocks of rat and human post-mortem spinal cords. We describe how to
      prepare and process those tissues, how to identify and dissect the ependymal
      region using Laser-Capture Microdissection (LCMD), and how to isolate and amplify
      RNA with different integrity states to finally obtain enough material for
      performing gene expression assays using Taqman(r) Low Density Arrays. LCMD
      technique maintains tissue integrity allowing for subsequent analysis without
      manipulation steps that may alter molecular properties of cells and the eventual
      loss of delicate cell types in comparison with other approaches that require
      previous disaggregation of the tissue and cell manipulation before isolation.

PMID- 29344869
TI  - Isolation of Amyloid Plaques and Neurofibrillary Tangles from Archived
      Alzheimer's Disease Tissue Using Laser-Capture Microdissection for Downstream
      Proteomics.
AB  - Here, we describe a new method that allows localized proteomics of amyloid
      plaques and neurofibrillary tangles (NFTs), which are the two pathological
      hallmarks of Alzheimer's disease (AD). Amyloid plaques and NFTs are visualized
      using immunohistochemistry and microdissected from archived, formalin-fixed
      paraffin-embedded (FFPE) human tissue samples using laser-capture
      microdissection. The majority of human tissue specimens are FFPE; hence the use
      of this type of tissue is a particular advantage of this technique.
      Microdissected tissue samples are solubilized with formic acid and
      deparaffinized, reduced, alkylated, proteolytically digested, and desalted. The
      resulting protein content of plaques and NFTs is determined using label-free
      quantitative LC-MS. This results in the unbiased and simultaneous quantification
      of ~900 proteins in plaques and ~500 proteins in NFTs. This approach permits
      downstream pathway and network analysis, hence providing a comprehensive overview
      of pathological protein accumulation found in neuropathological features in AD.

PMID- 29344870
TI  - Cell-Specific RNA Quantification in Human SN DA Neurons from Heterogeneous Post
      mortem Midbrain Samples by UV-Laser Microdissection and RT-qPCR.
AB  - Cell specificity of gene expression analysis is from particular relevance when
      the abundance of target cells is not homogeneous in the compared tissue samples,
      like it is the case, e.g., when comparing brain tissues from controls and in
      neurodegenerative disease states. While single-cell gene expression profiling is
      already a methodological challenge per se, it becomes even more prone to
      artifacts when analyzing individual cells from human post-mortem samples. Not
      only because human samples can never be matched as precisely as those from animal
      models, but also, because the RNA-quality that can be obtained from human samples
      usually displays a high range of variability. Here, we detail our most actual
      method for combining contact-free UV-laser microdissection (UV-LMD) with reverse
      transcription and quantitative PCR (RT-qPCR) that addresses all these issues. We
      specifically optimized our protocols to quantify and compare mRNA as well as
      miRNA levels in human neurons from post-mortem brain tissue. As human post-mortem
      tissue samples are never perfectly matched (e.g., in respect to distinct donor
      ages and RNA integrity numbers RIN), we refined data analysis by applying a
      linear mixed effects model to RT-qPCR data, which allows dissecting and
      subtracting linear contributions of distinct confounders on detected gene
      expression levels (i.e., RIN, age). All these issues were considered for
      comparative gene expression analysis in dopamine (DA) midbrain neurons of the
      Substantia nigra (SN) from controls and Parkinson's disease (PD) specimens, as
      the preferential degeneration of SN DA neurons in the pathological hallmark of
      PD. By utilizing the here-described protocol we identified that a variety of
      genes-encoding for ion channels, dopamine metabolism proteins, and PARK gene
      products-display a transcriptional dysregulation in remaining human SN DA neurons
      from PD brains compared to those of controls. We show that the linear mixed
      effects model allows further stratification of RT-qPCR data, as it indicated that
      differential gene expression of some genes was rather correlated with different
      ages of the analyzed human brain samples than with the disease state.

PMID- 29344871
TI  - Laser-Capture Microdissection for Layer-Specific Analysis of Enteric Ganglia.
AB  - The enteric nervous system (ENS) is the division of the autonomic nervous system
      that innervates the gastrointestinal (GI) tract and controls central intestinal
      functions such as peristalsis and fluid movement. Enteric nerve cell bodies
      (neurons and glia) are predominantly organized in ganglionated networks that are
      present along the entire length of the GI tract in multiple tissue layers. Most
      cell bodies are organized in the myenteric plexus allocated between the
      longitudinal and the circular muscle layers or in the submucosal plexus between
      muscle tissue and mucosa. The site-specific characteristics of these enteric
      nerve cells have traditionally been analyzed via imaging techniques. Laser
      capture microdissection (LCM) offers the prospect of site-specifically analyzing
      the gene expression profiles of these different subpopulations. This protocol
      addresses critical aspects of handling intestinal tissue for ENS dissection, such
      as the optimal quick-staining procedure, suitable laser settings, and limits of
      tissue material required to successfully dissect and analyze tissue layers for
      gene expression.

PMID- 29344872
TI  - A Laser Microdissection-Liquid Chromatography-Tandem Mass Spectrometry Workflow
      for Post-mortem Analysis of Brain Tissue.
AB  - Improved speed and sensitivity of mass spectrometry allow the simultaneous
      quantification of high numbers of proteins from increasingly smaller quantities
      of tissue sample. Quantitative data of the proteome is highly valuable for
      providing unbiased information on, for example, protein expression changes
      related to disease or identifying related biomarkers. In brain diseases the
      affected area can be small and pathogenic events can be related to a specific
      cell type in an otherwise heterogeneous tissue type. An emerging approach
      dedicated to analyzing this type of samples is laser micro-dissection (LMD)
      combined with LC-MS/MS into a single workflow. In this chapter, we describe
      different options for isolating tissue suitable for LC-MS/MS analysis.

PMID- 29344873
TI  - Laser-Capture Microdissection and RNA Extraction from Perfusion-Fixed Cartilage
      and Bone Tissue from Mice Implanted with Human iPSC-Derived MSCs in a Calvarial
      Defect Model.
AB  - Laser-capture microdissection (LCM) coupled to downstream RNA analysis poses
      unique difficulties for the evaluation of mineralized tissues. A rapid protocol
      was thus developed to enable sufficient integrity of bone and cartilage tissue
      for reliable sectioning, while minimizing RNA loss associated with prolonged
      decalcification and purification steps. Specifically, the protocol involves pump
      assisted, cardiac perfusion-fixation with paraformaldehyde, and moderate
      digestion of LCM-acquired tissue with proteinase K followed by DNase treatment
      and separation of RNA using magnetic beads. Reverse transcription and cDNA
      synthesis are performed immediately after RNA purification, without need for
      further protein removal.

PMID- 29344874
TI  - Laser Capture Microdissection-Based RNA-Seq of Barley Grain Tissues.
AB  - Spatiotemporal patterning throughout the plant body depends to a large degree on
      cell- and tissue-specific expression of genes. Subsequently, for a better
      understanding of cell and tissue differentiation processes during plant
      development it is important to conduct transcript analyses in individual cells or
      tissue types rather than in bulk tissues. Laser capture microdissection (LCM)
      provides a useful method for isolating specific cell types from complex tissue
      structures for downstream applications. Contrasting to mammalian cells, the
      texture of plant cells is more critical due to hard, cellulose-rich cell walls,
      large vacuoles, and air spaces which complicates tissue preparation and
      extraction of macromolecules, like DNA and RNA. In particular, developing barley
      seeds (i.e. grains) depict cell types with differences in osmomolarity
      (meristematic, differentiating and degenerating tissues) and contain high amounts
      of the main storage product starch. In this study, we report about methods
      allowing tissue-specific transcriptome profiling by RNA-seq of developing barley
      grain tissues from low-input RNA amounts. Details on tissue preparation, laser
      capture microdissection, RNA isolation, and linear mRNA amplification to produce
      high-quality samples for Illumina sequencing are provided. Particular emphasis
      was placed on the influence of the mRNA amplification step on the transcriptome
      data and the fidelity of deduced expression levels obtained by the developed
      methods. Analysis of RNA-seq data confirmed sample processing as a highly
      reliable and reproducible procedure that was also used for transcriptome analyses
      of different tissue types from barley plants.

PMID- 29344875
TI  - Development of a Prognostic Prediction Model to Determine Severe Dengue in
      Children.
AB  - OBJECTIVE: To develop a prognostic prediction model using the seven warning signs
      highlighted by WHO revised Dengue fever classification 2009 to determine severe
      dengue in children. METHODS: In this prospective analytical study conducted in a
      tertiary care centre, consecutive sampling of all children aged 1mo to 12y
      admitted with serologically confirmed Dengue was done from May 2015 through
      August 2016. After excluding 27 patients with co-infections and co-morbidities,
      359 patients were followed up daily to assess clinical and laboratory progression
      till discharge/ death. Independent predictors were abdominal pain or tenderness,
      persistent vomiting, lethargy, mucosal bleed, clinical fluid accumulation,
      hepatomegaly >2 cm and rising hematocrit concurrent with platelet count <100 *
      109/L. Outcome measure was severe dengue defined as per WHO guidelines 2009.
      RESULTS: Among 359 children, 93 progressed to severe dengue. In univariate
      analysis, significant predictors were clinical fluid accumulation (OR 4.773, p =
      0.000, 95%CI 2.511-9.075), persistent vomiting (OR 1.944, p = 0.010, 95%CI 1.170
      3.225), mucosal bleed (OR 2.045, p = 0.019, 95%CI 1.127-3.711) and hematocrit
      >=0.40 concurrent with platelet count <100 * 109/L (OR 2.985, p = 0.000, 95%CI
      1.783-4.997). The final multivariable model included clinical fluid accumulation
      (aOR 3.717, p = 0.000, 95%CI 1.901-7.269), hematocrit >=0.40 concurrent with
      platelet count <100 * 109/L (aOR 2.252, p = 0.004, 95%CI 1.302-3.894) and
      persistent vomiting (p = 0.056) as predictors of severe dengue. CONCLUSIONS:
      Among seven WHO warning signs, predictors of severe dengue as suggested by the
      present multivariable prediction model include clinical fluid accumulation,
      persistent vomiting and hematocrit >=0.40 concurrent with platelet count <100 *
      109/L.

PMID- 29344877
TI  - A bioluminescent test system reveals valuable antioxidant properties of
      lactobacillus strains from human microbiota.
AB  - Oxidative stress cause serious damages in human organism resulting in multiple
      diseases. Antioxidant therapy includes diet, the use of chemical agents or
      commensal bacteria such as lactobacilli. This study aims to evaluate the
      antioxidant (AO) activity of cell-free culture supernatants of lactobacilli,
      isolated from different parts of the human body. A test system based on
      Escherichia coli MG1655 strains carrying plasmids encoding luminescent biosensors
      pSoxS-lux and pKatG-lux inducible by superoxide anion and hydrogen peroxide,
      respectively, was used to analyze cell-free culture supernatants of lactobacilli.
      Bioluminescent detection systems are suitable for quick screening of AO activity
      of lactobacilli. The majority of strains (51 out of 81) belonging to six
      different species demonstrated various levels of antioxidant activity. This
      activity was confirmed using the trolox equivalent method. The genome of one of
      the strains showing high AO activity was sequenced, and the genes putatively
      involved in AO capacity were determined. Potencies of standard AO and CFS from
      the most active Lactobacillus strains. Percentages of decrease in the detected
      luminescence (IAO%) in the presence of AO or CFS are presented. L. br.-L. brevis,
      L. pl. -L. plantarum, L. rh.-L. rhamnosus.

PMID- 29344876
TI  - Biosimilarity and Interchangeability: Principles and Evidence: A Systematic
      Review.
AB  - BACKGROUND: The efficacy, safety and immunogenicity risk of switching between an
      originator biologic and a biosimilar or from one biosimilar to another are of
      potential concern. OBJECTIVES: The aim was to conduct a systematic literature
      review of the outcomes of switching between biologics and their biosimilars and
      identify any evidence gaps. METHODS: A systematic literature search was conducted
      in PubMed, EMBASE and Cochrane Library from inception to June 2017. Relevant
      societal meetings were also checked. Peer-reviewed studies reporting efficacy
      and/or safety data on switching between originator and biosimilar products or
      from one biosimilar to another were selected. Studies with fewer than 20 switched
      patients were excluded. Data were extracted on interventions, study population,
      reason for treatment switching, efficacy outcomes, safety and anti-drug
      antibodies. RESULTS: The systematic literature search identified 63 primary
      publications covering 57 switching studies. The reason for switching was reported
      as non-medical in 50 studies (23 clinical, 27 observational). Seven studies (all
      observational) did not report whether the reasons for switching were medical or
      non-medical. In 38 of the 57 studies, fewer than 100 patients were switched.
      Follow-up after switching went beyond 1 year in eight of the 57 studies. Of the
      57 studies, 33 included statistical analysis of disease activity or patient
      outcomes; the majority of these studies found no statistically significant
      differences between groups for main efficacy parameters (based on P < 0.05 or
      predefined acceptance ranges), although some studies observed changes for some
      parameters. Most studies reported similar safety profiles between groups.
      CONCLUSIONS: There are important evidence gaps around the safety of switching
      between biologics and their biosimilars. Sufficiently powered and appropriately
      statistically analysed clinical trials and pharmacovigilance studies, with long
      term follow-ups and multiple switches, are needed to support decision-making
      around biosimilar switching.

PMID- 29344878
TI  - Gemcitabine and Taxane Adjuvant Therapy with Chemoradiation in Resected
      Pancreatic Cancer: A Novel Strategy for Improved Survival?
AB  - BACKGROUND: Gemcitabine-taxane combination chemotherapy has demonstrated a
      survival benefit clinically in metastatic pancreatic cancer (PC). The authors
      present their experience with gemcitabine and docetaxel (gem/tax)-based adjuvant
      treatment (Rx) after surgery with curative intent. METHODS: Patients with de novo
      resectable PC from January 2010 to December 2015 were identified from the
      authors' institutional database and registry. The study included only patients
      who received gem/tax as their initial Rx administered exclusively at the authors'
      institution with or without chemoradiation (CRTx). Survival analysis was
      performed using Kaplan-Meier methods, and prognostic factors were investigated by
      Cox proportional hazard modeling. RESULTS: Of 102 patients identified, 58 met the
      study criteria. The median age at diagnosis was 65 years, with 55% of the
      patients undergoing an R1 resection (margin <= 1 mm). Tumor characteristics
      included a median tumor size of 28 mm, a poor differentiation rate of 54%, and a
      lymph node positivity of 67%. Most of the patients (90%, 52/58) completed 80% or
      more of the 24 week Rx. Of these patients, 71% received post-gem/tax CRTx Rx.
      Grade 3 or 4 toxicity was observed in 52% of the patients. The median follow-up
      period was 51.2 months, and the observed median overall survival (OS) was 52
      months [95% confidence interval (CI) 27.4-not reached]. The actuarial 5-year OS
      was 49% (95% CI 33.7-63.4%). In the multivariate analysis, an R1 resection and
      American Joint Committee on Cancer (AJCC) stage 2 versus stage 1 disease were
      negatively associated with OS, whereas administration of CRTx was positively
      associated with OS. CONCLUSIONS: Adjuvant gem/tax with or without CRTx is
      feasible, with a favorable OS. Future prospective studies of gem/taxane-based
      adjuvant Rx for PC are warranted.

PMID- 29344879
TI  - Antiplatelet (aspirin) therapy as a new option in the treatment of vasculogenic
      erectile dysfunction: a prospective randomized double-blind placebo-controlled
      study.
AB  - PURPOSE: To investigate the efficiency of antiplatelet (aspirin) therapy in
      vasculogenic erectile dysfunction (VED) patients with a high mean platelet
      volume. METHODS: A total of 184 patients diagnosed with VED between the ages of
      18 and 76 were randomly divided into two groups and treated for 6 weeks [group 1:
      120 patients (mean age 48.3), aspirin 100 mg/day; group 2: 64 patients (mean age
      47.7), placebo 100 mg/day]. The changes from baseline to end point in erectile
      function scores on the International Index of Erectile Function (IIEF-EF) and the
      number of patients who answered "yes" to questions 2 and 3 of the sexual
      encounter profile (SEP) were compared statistically. RESULTS: The mean baseline
      IIEF-EF scores in groups 1 and 2 were 14.1 +/- 4.9 and 14.3 +/- 5.2, respectively
      (p = 0.7966), the number of patients who answered "yes" to SEP-2 was 62 (51.6%)
      in group 1 and 32 (50%) in group 2 (p = 0.8366), and the number of patients who
      answered "yes" to SEP-3 was 38 (31.6%) in group 1 and 20 (31.2%) in group 2 (p =
      0.9557). In the aspirin group, the changes from baseline to end point in the IIEF
      EF, SEP-2, and SEP-3 scores were 7.2, 36.6, and 46.6%, respectively. In the
      placebo group, these changes were 2.0, 9.4, and 12.5%, respectively. When
      compared with the placebo group, aspirin-treated subjects showed a significant
      improvement in all three efficacy measures (p < 0.0001). CONCLUSIONS: 100 mg of
      aspirin administered once a day significantly improved EF in men with VED.

PMID- 29344880
TI  - The role of zinc in urinary stone disease.
AB  - In recent years, the role of trace elements in lithogenesis has received steadily
      increasing attention. It is well documented that some trace elements can
      influence the morphology and speed of the crystallization process. Zinc has been
      found in significant amounts in calcium stones relative or organic stones (uric
      acid and cystine), probably substituting calcium in crystals because of their
      similarity in charge and size. High Zn levels are present in carbapatite of
      Randal's plaques suggesting that zinc could promote calcium phosphate deposition
      in the medullar interstitium. Large-scale epidemiological studies have found an
      association of increased dietary zinc intake with increased risk of
      nephrolithiasis in adults but not in adolescents. Most studies examining urinary
      zinc levels in adults have reported increased urinary Zn excretion in stone
      formers. In an experimental model of organic crystal formation produced by
      silencing xanthine dehydrogenase in Drosophila fly, maneuvers that reduce Zn
      excretion have shown to reduce crystal formation in the lumen of the Malpighian
      tubules. This is curious because this is not a model of calcium stone formation.
      Finally, zinc supplementation has been associated with increased admissions for
      urinary lithiasis in men, but no change in calcium stone formation in children.
      Perhaps, some of these contradicting findings can be explained in part by the in
      vitro effect of zinc on the type and amount of calcium phosphate formed: At low
      concentrations, Zn inhibited the crystal growth of dicalcium phosphate dihydrate,
      octacalcium phosphate, and apatite, and at higher concentrations, it promoted the
      formation of amorphous calcium phosphate. Thus, further studies are needed to see
      whether manipulation of Zn metabolism can inhibit calcium stone formation.

PMID- 29344882
TI  - Detection of Combinatorial Mutational Patterns in Human Cancer Genomes by
      Exclusivity Analysis.
AB  - Cancer genes may tend to mutate in a co-mutational or mutually exclusive manner
      in a tumor sample of a specific cancer, which constitute two known combinatorial
      mutational patterns for a given gene set. Previous studies have established that
      genes functioning in different signaling pathways can mutate in the same sample,
      i.e., a tumor from one patient, while genes operating in the same pathway are
      rarely mutated in the same cancer genome. Therefore, reliable identification of
      combinatorial mutational patterns of candidate cancer genes has important
      ramifications in inferring signaling network modules in a particular cancer type.
      While algorithms for discovering mutated driver pathways based on mutual
      exclusivity of mutations in cancer genes have been proposed, a systematic
      pipeline for identifying both co-mutational and mutually exclusive patterns with
      rational significance estimation is still lacking. Here, we describe a reliable
      framework with detailed procedures to simultaneously explore both combinatorial
      mutational patterns from public cross-sectional gene mutation data.

PMID- 29344883
TI  - Discovering Altered Regulation and Signaling Through Network-based Integration of
      Transcriptomic, Epigenomic, and Proteomic Tumor Data.
AB  - With the extraordinary rise in available biological data, biologists and
      clinicians need unbiased tools for data integration in order to reach accurate,
      succinct conclusions. Network biology provides one such method for high
      throughput data integration, but comes with its own set of algorithmic problems
      and needed expertise. We provide a step-by-step guide for using Omics Integrator,
      a software package designed for the integration of transcriptomic, epigenomic,
      and proteomic data. Omics Integrator can be found at
      http://fraenkel.mit.edu/omicsintegrator .

PMID- 29344881
TI  - The impact of exercise on physical function, cardiovascular outcomes and quality
      of life in chronic kidney disease patients: a systematic review.
AB  - The prevalence of chronic kidney disease (CKD) and end-stage renal disease (ESRD)
      is increasing steadily. CKD does not only relate to morbidity and mortality but
      also has impact on quality of life, depression and malnutrition. Such patients
      often have significantly decreased physical activity. Recent evidence suggests
      that low physical activity is associated with morbidity, mortality, muscle
      atrophy, quality of life impairment, cardiovascular outcomes and depression.
      Based on this, it is now recommended to regularly improve the physical activity
      of these patients. Furthermore, studies have shown the beneficial effects of
      various exercise programs with respect to outcomes such as low physical activity
      muscle atrophy, quality of life, cardiovascular outcomes and depression. Despite
      these encouraging findings, the subject is still under debate, with various
      aspects still unknown. In this review, we tried to critically summarize the
      existing studies, to explore mechanisms and describe future perspectives
      regarding physical activity in CKD/ESRD patients.

PMID- 29344884
TI  - Analyzing DNA Methylation Patterns During Tumor Evolution.
AB  - Epigenetic modifications play a key role in cellular development and
      tumorigenesis. Recent large-scale genomic studies have shown that mutations in
      players of the epigenetic machinery and concomitant perturbation of epigenomic
      patterning are frequent events in tumors. Among epigenetic marks, DNA methylation
      is one of the best studied. Hyper- and hypo-methylation events of specific
      regulatory elements (such as promoters and enhancers) are sometimes thought to be
      correlated with expression of nearby genes. High-throughput bisulfite converted
      sequencing is currently the technology of choice for studying DNA methylation in
      base-pair resolution and on whole-genome scale. Such broad and high-resolution
      coverage investigations of the epigenome provide unprecedented opportunities to
      analyze DNA methylation patterns, which are correlated with tumorigenesis, tumor
      evolution, and tumor progression. However, few computational pipelines are
      available to the public to perform systematic DNA methylation analysis. Utilizing
      open source tools, we here describe a comprehensive computational methodology to
      thoroughly analyze DNA methylation patterns during tumor evolution based on
      bisulfite converted sequencing data, including intra-tumor methylation
      heterogeneity.

PMID- 29344885
TI  - MicroRNA Networks in Breast Cancer Cells.
AB  - A variety of molecular techniques can be used in order to unravel the molecular
      composition of cells. In particular, the microarray technology has been used to
      identify novel biomarkers that may be useful in the diagnosis, prognosis, or
      treatment of cancer. The microarray technology is ideal for biomarker discovery
      as it allows for the screening of a large number of molecules at once. In this
      review, we focus on microRNAs (miRNAs) which are key molecules in cells and
      regulate gene expression post-transcriptionally. miRNAs are small, single
      stranded RNA molecules that bind to complementary mRNAs. Binding of miRNAs to
      mRNAs leads either to degradation, or translational inhibition of the target
      mRNA. Roughly one third of all the mRNAs are postulated to be regulated by
      miRNAs. miRNAs are known to be deregulated in different types of cancer,
      including breast cancer, and it has been demonstrated that deregulation of
      several miRNAs can be used as biological markers in cancer. miRNA expression can
      for example discriminate between normal, benign and malignant breast tissue, and
      between different breast cancer subtypes.In the post-genomic era, an important
      task of molecular biology is to understand gene regulation in the context of
      biological networks. Because miRNAs have such a pronounced role in cells, it is
      pivotal to understand the mechanisms that underlie their control, and to identify
      how miRNAs influence cancer development and progression.

PMID- 29344886
TI  - Identifying Genetic Dependencies in Cancer by Analyzing siRNA Screens in Tumor
      Cell Line Panels.
AB  - Loss-of-function screening using RNA interference or CRISPR approaches can be
      used to identify genes that specific tumor cell lines depend upon for survival.
      By integrating the results from screens in multiple cell lines with molecular
      profiling data, it is possible to associate the dependence upon specific genes
      with particular molecular features (e.g., the mutation of a cancer driver gene,
      or transcriptional or proteomic signature). Here, using a panel of kinome-wide
      siRNA screens in osteosarcoma cell lines as an example, we describe a
      computational protocol for analyzing loss-of-function screens to identify genetic
      dependencies associated with particular molecular features. We describe the steps
      required to process the siRNA screen data, integrate the results with genotypic
      information to identify genetic dependencies, and finally the integration of
      protein-protein interaction data to interpret these dependencies.

PMID- 29344888
TI  - Perseus: A Bioinformatics Platform for Integrative Analysis of Proteomics Data in
      Cancer Research.
AB  - Mass spectrometry-based proteomics is a continuously growing field marked by
      technological and methodological improvements. Cancer proteomics is aimed at
      pursuing goals such as accurate diagnosis, patient stratification, and biomarker
      discovery, relying on the richness of information of quantitative proteome
      profiles. Translating these high-dimensional data into biological findings of
      clinical importance necessitates the use of robust and powerful computational
      tools and methods. In this chapter, we provide a detailed description of standard
      analysis steps for a clinical proteomics dataset performed in Perseus, a software
      for functional analysis of large-scale quantitative omics data.

PMID- 29344889
TI  - Quantitative Analysis of Tyrosine Kinase Signaling Across Differentially Embedded
      Human Glioblastoma Tumors.
AB  - Glioblastoma is the most aggressive primary brain tumor with a poor mean survival
      even with the current standard of care. Kinase signaling analyses of clinical
      glioblastoma samples provide a physiologically relevant view of oncogenic
      signaling networks. Here, we describe the methods that enable the quantification
      of protein expression profiles and phosphotyrosine signaling across flash frozen
      and optimal cutting temperature (OCT) compound embedded tumor specimens. The data
      derived from these experiments can be used to identify the intra- and inter
      patient heterogeneity present in these tumors. Correlation and functional
      analyses on the quantitative protein expression and phosphotyrosine signaling
      data obtained from clinical samples can be used to identify tyrosine kinase
      signaling networks present in these tumors and reveal the differential expression
      of functionally related proteins. This chapter provides the quantitative mass
      spectrometry methods required for the identification of in vivo oncogenic
      signaling networks from human tumor specimens.

PMID- 29344887
TI  - Phosphoproteomics-Based Profiling of Kinase Activities in Cancer Cells.
AB  - Cellular signaling, predominantly mediated by phosphorylation through protein
      kinases, is found to be deregulated in most cancers. Accordingly, protein kinases
      have been subject to intense investigations in cancer research, to understand
      their role in oncogenesis and to discover new therapeutic targets. Despite great
      advances, an understanding of kinase dysfunction in cancer is far from complete.A
      powerful tool to investigate phosphorylation is mass-spectrometry (MS)-based
      phosphoproteomics, which enables the identification of thousands of
      phosphorylated peptides in a single experiment. Since every phosphorylation event
      results from the activity of a protein kinase, high-coverage phosphoproteomics
      data should indirectly contain comprehensive information about the activity of
      protein kinases.In this chapter, we discuss the use of computational methods to
      predict kinase activity scores from MS-based phosphoproteomics data. We start
      with a short explanation of the fundamental features of the phosphoproteomics
      data acquisition process from the perspective of the computational analysis.
      Next, we briefly review the existing databases with experimentally verified
      kinase-substrate relationships and present a set of bioinformatic tools to
      discover novel kinase targets. We then introduce different methods to infer
      kinase activities from phosphoproteomics data and these kinase-substrate
      relationships. We illustrate their application with a detailed protocol of one of
      the methods, KSEA (Kinase Substrate Enrichment Analysis). This method is
      implemented in Python within the framework of the open-source Kinase Activity
      Toolbox (kinact), which is freely available at http://github.com/saezlab/kinact/
      .

PMID- 29344890
TI  - Prediction of Clinical Endpoints in Breast Cancer Using NMR Metabolic Profiles.
AB  - Metabolic profiles reflect biological conditions as a result of biochemical
      changes within a living system. It is therefore possible to associate metabolic
      signatures with clinical endpoints of diseases, such as breast cancer. Nuclear
      magnetic resonance (NMR) spectroscopy is one of the most common techniques used
      for metabolic profiling, and produces high dimensional datasets from which
      meaningful biological information can be extracted. Here, we present an overview
      of data analysis techniques used to achieve this, describing key steps in the
      procedure. Moreover, examples of clinical endpoints of interest are provided.
      Although these are specific for breast cancer, the procedures for the analysis of
      NMR spectra as described here are applicable to any type of cancer and to other
      diseases.

PMID- 29344891
TI  - Stochastic and Deterministic Models for the Metastatic Emission Process:
      Formalisms and Crosslinks.
AB  - Although the detection of metastases radically changes prognosis of and treatment
      decisions for a cancer patient, clinically undetectable micrometastases hamper a
      consistent classification into localized or metastatic disease. This chapter
      discusses mathematical modeling efforts that could help to estimate the
      metastatic risk in such a situation. We focus on two approaches: (1) a stochastic
      framework describing metastatic emission events at random times, formalized via
      Poisson processes, and (2) a deterministic framework describing the
      micrometastatic state through a size-structured density function in a partial
      differential equation model. Three aspects are addressed in this chapter. First,
      a motivation for the Poisson process framework is presented and modeling
      hypotheses and mechanisms are introduced. Second, we extend the Poisson model to
      account for secondary metastatic emission. Third, we highlight an inherent
      crosslink between the stochastic and deterministic frameworks and discuss its
      implications. For increased accessibility the chapter is split into an informal
      presentation of the results using a minimum of mathematical formalism and a
      rigorous mathematical treatment for more theoretically interested readers.

PMID- 29344892
TI  - Mechanically Coupled Reaction-Diffusion Model to Predict Glioma Growth:
      Methodological Details.
AB  - Biophysical models designed to predict the growth and response of tumors to
      treatment have the potential to become a valuable tool for clinicians in care of
      cancer patients. Specifically, individualized tumor forecasts could be used to
      predict response or resistance early in the course of treatment, thereby
      providing an opportunity for treatment selection or adaption. This chapter
      discusses an experimental and modeling framework in which noninvasive imaging
      data is used to initialize and parameterize a subject-specific model of tumor
      growth. This modeling approach is applied to an analysis of murine models of
      glioma growth.

PMID- 29344893
TI  - Profiling Tumor Infiltrating Immune Cells with CIBERSORT.
AB  - Tumor infiltrating leukocytes (TILs) are an integral component of the tumor
      microenvironment and have been found to correlate with prognosis and response to
      therapy. Methods to enumerate immune subsets such as immunohistochemistry or flow
      cytometry suffer from limitations in phenotypic markers and can be challenging to
      practically implement and standardize. An alternative approach is to acquire
      aggregative high dimensional data from cellular mixtures and to subsequently
      infer the cellular components computationally. We recently described CIBERSORT, a
      versatile computational method for quantifying cell fractions from bulk tissue
      gene expression profiles (GEPs). Combining support vector regression with prior
      knowledge of expression profiles from purified leukocyte subsets, CIBERSORT can
      accurately estimate the immune composition of a tumor biopsy. In this chapter, we
      provide a primer on the CIBERSORT method and illustrate its use for
      characterizing TILs in tumor samples profiled by microarray or RNA-Seq.

PMID- 29344894
TI  - Systems Biology Approaches in Cancer Pathology.
AB  - The complex network of the tissue system, in both pre-neoplastic tissues and
      tumors, demonstrates the need for a systems biology approach to cancer pathology,
      in which quantification of key tissue system processes is combined with
      informatics tools to produce actionable scores to aid clinical decision-making. A
      systems biology approach to cancer pathology enables integration of key system
      features that are relevant to diagnoses, patient outcomes, and responses to
      therapies. Key tissue system features relevant to cancer pathology include
      molecular and morphologic abnormalities in epithelia, cellular changes in the
      stroma such as immune infiltrates, and relationships between components of the
      system, such as interactions and spatial relationships between epithelial and
      stromal components, and also between specific immune cell subsets. Here, we
      describe a method for objective quantification of multiple epithelial and stromal
      biomarkers in the context of tissue architecture to generate a high dimensional
      tissue profile that can be used to build multivariable predictive models for
      cancer pathology.

PMID- 29344895
TI  - Bioinformatics Approaches to Predict Drug Responses from Genomic Sequencing.
AB  - Fulfilling the promises of precision medicine will depend on our ability to
      create patient-specific treatment regimens. Therefore, being able to translate
      genomic sequencing into predicting how a patient will respond to a given drug is
      critical. In this chapter, we review common bioinformatics approaches that aim to
      use sequencing data to predict sample-specific drug susceptibility. First, we
      explain the importance of customized drug regimens to the future of medical care.
      Second, we discuss the different public databases and community efforts that can
      be leveraged to develop new methods for identifying new predictive biomarkers.
      Third, we cover the basic methods that are currently used to identify markers or
      signatures of drug response, without any prior knowledge of the drug's mechanism
      of action. We further discuss how one can integrate knowledge about drug targets,
      mechanisms, and predictive markers to better estimate drug response in a diverse
      set of samples. We begin this section with a primer on popular methods to
      identify targets and mechanism of action for new small molecules. This discussion
      also includes a set of computational methods that incorporate other drug
      features, which do not relate to drug-induced genetic changes or sequencing data
      such as drug structures, side-effects, and efficacy profiles. Those additional
      drug properties can aid in gaining higher accuracy for the identification of drug
      target and mechanism of action. We then progress to discuss using these targets
      in combination with disease-specific expression patterns, known pathways, and
      genetic interaction networks to aid drug choice. Finally, we conclude this
      chapter with a general overview of machine learning methods that can integrate
      multiple pieces of sequencing data along with prior drug or biological knowledge
      to drastically improve response prediction.

PMID- 29344896
TI  - A Robust Optimization Approach to Cancer Treatment under Toxicity Uncertainty.
AB  - The design of optimal protocols plays an important role in cancer treatment.
      However, in clinical applications, the outcomes under the optimal protocols are
      sensitive to variations of parameter settings such as drug effects and the
      attributes of age, weight, and health conditions in human subjects. One approach
      to overcoming this challenge is to formulate the problem of finding an optimal
      treatment protocol as a robust optimization problem (ROP) that takes parameter
      uncertainty into account. In this chapter, we describe a method to model toxicity
      uncertainty. We then apply a mixed integer ROP to derive the optimal protocols
      that minimize the cumulative tumor size. While our method may be applied to other
      cancers, in this work we focus on the treatment of chronic myeloid leukemia (CML)
      with tyrosine kinase inhibitors (TKI). For simplicity, we focus on one particular
      mode of toxicity arising from TKI therapy, low blood cell counts, in particular
      low absolute neutrophil count (ANC). We develop optimization methods for locating
      optimal treatment protocols assuming that the rate of decrease of ANC varies
      within a given interval. We further investigated the relationship between
      parameter uncertainty and optimal protocols. Our results suggest that the dosing
      schedule can significantly reduce tumor size without recurrence in 360 weeks
      while insuring that toxicity constraints are satisfied for all realizations of
      uncertain parameters.

PMID- 29344897
TI  - Modeling of Interactions between Cancer Stem Cells and their Microenvironment:
      Predicting Clinical Response.
AB  - Mathematical models of cancer stem cells are useful in translational cancer
      research for facilitating the understanding of tumor growth dynamics and for
      predicting treatment response and resistance to combined targeted therapies. In
      this chapter, we describe appealing aspects of different methods used in
      mathematical oncology and discuss compelling questions in oncology that can be
      addressed with these modeling techniques. We describe a simplified version of a
      model of the breast cancer stem cell niche, illustrate the visualization of the
      model, and apply stochastic simulation to generate full distributions and average
      trajectories of cell type populations over time. We further discuss the advent of
      single-cell data in studying cancer stem cell heterogeneity and how these data
      can be integrated with modeling to advance understanding of the dynamics of
      invasive and proliferative populations during cancer progression and response to
      therapy.

PMID- 29344898
TI  - Methods for High-throughput Drug Combination Screening and Synergy Scoring.
AB  - Gene products or pathways that are aberrantly activated in cancer but not in
      normal tissue hold great promises for being effective and safe anticancer
      therapeutic targets. Many targeted drugs have entered clinical trials but so far
      showed limited efficacy mostly due to variability in treatment responses and
      often rapidly emerging resistance. Toward more effective treatment options, we
      will need multi-targeted drugs or drug combinations, which selectively inhibit
      the viability and growth of cancer cells and block distinct escape mechanisms for
      the cells to become resistant. Functional profiling of drug combinations requires
      careful experimental design and robust data analysis approaches. At the Institute
      for Molecular Medicine Finland (FIMM), we have developed an experimental
      computational pipeline for high-throughput screening of drug combination effects
      in cancer cells. The integration of automated screening techniques with advanced
      synergy scoring tools allows for efficient and reliable detection of synergistic
      drug interactions within a specific window of concentrations, hence accelerating
      the identification of potential drug combinations for further confirmatory
      studies.

PMID- 29344901
TI  - Imaging Characteristics and First Experience of [68Ga]THP-PSMA, a Novel Probe for
      Rapid Kit-Based Ga-68 Labeling and PET Imaging: Comparative Analysis with
      [68Ga]PSMA I&T.
AB  - PURPOSE: [68Ga]Trishydroxypyridinone (THP)-prostate-specific membrane antigen
      (PSMA) is a novel tracer that can be labeled in one step by cold reconstitution
      of a kit with unprocessed generator eluate, targeting PSMA via the lysine-urea
      glutamate (KuE) motif. The aim of this study was to evaluate the human imaging
      characteristics of [68Ga]THP-PSMA. PROCEDURES: [68Ga]THP-PSMA positron emission
      tomography (PET)/x-ray computed tomography (CT) was performed in 25 patients with
      biochemical recurrence after radical prostatectomy for prostate cancer. Urinary
      and biliary excretion and tumor lesion uptake were quantified using standardized
      uptake values (SUVs). Imaging characteristics were assessed in terms of non
      target organ uptake, background activity, target-to-background ratios (TBRs) of
      tumor lesions, and frequency of bladder halo artifacts. Findings were compared to
      a matched cohort of 25 patients undergoing PET/CT with the established agent
      [68Ga]PSMA I&T. RESULTS: Physiologic uptake of [68Ga]THP-PSMA was significantly
      lower in salivary glands (P < 0.0001), liver (P < 0.0001), spleen (P < 0.0001),
      and kidneys (P < 0.0001) than with [68Ga]PSMA I&T. While biliary tracer excretion
      of [68Ga]THP-PSMA was negligible, urinary tracer excretion of [68Ga]THP-PSMA was
      fast, and significantly higher than for [68Ga]PSMA I&T, contributing to a higher
      frequency of bladder artifacts. Malignant lesion uptake of [68Ga]THP-PSMA
      assessed as either SUV or TBR was significantly lower than with [68Ga]PSMA I&T.
      CONCLUSION: [68Ga]THP-PSMA yields suitable in vivo uptake characteristics. The
      simplified synthesis method for [68Ga]THP-PSMA may facilitate wider application
      and higher patient throughput with PSMA imaging. However, direct intraindividual
      comparison studies are needed to assess the relative performance of [68Ga]THP
      PSMA vs other PSMA ligands in terms of clinical detection rate and image quality.

PMID- 29344902
TI  - Occupational exposure to electromagnetic fields in magnetic resonance
      environment: basic aspects and review of exposure assessment approaches.
AB  - The purpose of this review is to make a contribution to build a comprehensive
      knowledge of the main aspects related to the occupational exposure to
      electromagnetic fields (EMFs) in magnetic resonance imaging (MRI) environments.
      Information has been obtained from original research papers published in
      international peer-reviewed journals in the English language and from documents
      published by governmental bodies and authorities. An overview of the occupational
      exposure scenarios to static magnetic fields, motion-induced, time-varying
      magnetic fields, and gradient and radiofrequency fields is provided, together
      with a summary of the relevant regulation for limiting exposure. A particular
      emphasis is on reviewing the main EMF exposure assessment approaches found in the
      literature. Exposure assessment is carried out either by measuring the
      unperturbed magnetic fields in the MRI rooms, or by personal monitoring
      campaigns, or by the use of numerical methods. A general lack of standardization
      of the procedures and technologies adopted for exposure assessment has emerged,
      which makes it difficult to perform a direct comparison of results from different
      studies carried out by applying different assessment strategies. In conclusion,
      exposure assessment approaches based on data collection and numerical models need
      to be better defined in order to respond to specific research questions. That
      would provide for a more complete characterization of the exposure patterns and
      for identification of the factors determining the exposure variability. Graphical
      abstract Main approaches adopted in the literature to perform occupational
      exposure assessment to electromagnetic fields (EMFs) in magnetic resonance
      imaging (MRI) environments. SMF: static magnetic field; GMF: gradient magnetic
      fields; RF: radio-frequencies.

PMID- 29344903
TI  - Nuclear genes involved in mitochondrial diseases caused by instability of
      mitochondrial DNA.
AB  - Mitochondrial diseases are defined by a respiratory chain dysfunction and in most
      of the cases manifest as multisystem disorders with predominant expression in
      muscles and nerves and may be caused by mutations in mitochondrial (mtDNA) or
      nuclear (nDNA) genomes. Most of the proteins involved in respiratory chain
      function are nuclear encoded, although 13 subunits of respiratory chain complexes
      (together with 2 rRNAs and 22 tRNAs necessary for their translation) encoded by
      mtDNA are essential for cell function. nDNA encodes not only respiratory chain
      subunits but also all the proteins responsible for mtDNA maintenance, especially
      those involved in replication, as well as other proteins necessary for the
      transcription and copy number control of this multicopy genome. Mutations in
      these genes can cause secondary instability of the mitochondrial genome in the
      form of depletion (decreased number of mtDNA molecules in the cell), vast
      multiple deletions or accumulation of point mutations which in turn leads to
      mitochondrial diseases inherited in a Mendelian fashion. The list of genes
      involved in mitochondrial DNA maintenance is long, and still incomplete.

PMID- 29344904
TI  - MGMT assessment in pituitary adenomas: comparison of different
      immunohistochemistry fixation chemicals.
AB  - PURPOSE: Despite the established role of O6-methyl-guanine-DNA methyltransferase
      (MGMT) as a marker for temozolomide response, consensus of the most reliable
      method to assess MGMT expression in pituitary adenomas is still missing.
      Currently, immunohistochemistry (IHC) assessment of formaldehyde fixed tissue
      samples is most widely used in a semiquantitative description. As formaldehyde
      fails to completely preserve nucleic acids, RCL2, an alcohol-based formaldehyde
      free fixative, has been proposed as a more reliable alternative in terms of cell
      stability. Furthermore, as the current method of IHC is semiquantitative and
      observer-dependent, pyrosequencing, an objective tool to evaluate the methylation
      status of the MGMT promoter, has emerged as a reliable and accurate alternative.
      The aim of this study was to validate the current IHC method for assessment of
      MGMT protein expression in pituitary adenomas. METHODS: The tissue samples of 8
      macroadenomas with positive IHC MGMT expression (> 50%) were investigated: first,
      we compared the time dependent stability of MGMT protein expression after
      pituitary adenoma removal between formaldehyde vs. RCL2. Then, we compared
      positive IHC MGMT expression with methylated promoter status using
      pyrosequencing. RESULTS: In the first 12 h after adenoma removal, tissue samples
      remained MGMT positive in significantly more samples when fixated with
      formaldehyde than with RCL2, respectively (96 vs. 81%, p = 0.025). CONCLUSION:
      Our data confirm that the current method using formaldehyde tissue fixation and
      IHC reveals stable and reliable results of MGMT assessment in pituitary adenomas.

PMID- 29344905
TI  - Management of NFAs: medical treatment.
AB  - INTRODUCTION: Non-functioning pituitary adenomas (NFPAs) are in general large
      tumors that present with symptoms secondary to local pressure on adjacent
      structures. Transsphenoidal surgery is the first line of treatment but residual
      tumor mass is often detected post-operatively. Medical therapy, in any stage of
      tumor management, is not well established. METHODS: A literature search was
      performed to review the available data on medical treatment of NFPAs. RESULTS:
      Medications investigated for the treatment of NFPAs include dopamine receptor
      agonists (DA) and somatostatin receptor ligands. Randomized controlled trials are
      lacking, but available data suggest that DA have a positive effect on tumor
      remnant stabilization after surgery and could be considered in this setting.
      Temozolomide is reserved for aggressive tumors, although future studies are
      required. CONCLUSIONS: NFPA are often not amenable to complete surgical
      resection. Conservative follow-up after surgery is associated with a high
      prevalence of tumor remnant progression. DA therapy may prevent residual tumor
      enlargement in over 85% of these patients, with a substantial consequent
      reduction in the need for repeat surgery or radiation therapy. It is our view
      that DA treatment should be routinely considered for the management of NFPA
      patients with incompletely resected tumors.

PMID- 29344906
TI  - Mortality in patients with non-functioning pituitary adenoma.
AB  - Non-functioning pituitary adenomas (NFA) are benign pituitary neoplasms not
      associated with clinical evidence of hormonal hypersecretion. A substantial
      number of patients with NFA have morbidities related to the tumor and possible
      recurrence(s), as well as to the treatments offered. Studies assessing the long
      term mortality of patients with NFA are limited. Based on the published
      literature of the last two decades, overall, the standardized mortality ratios in
      this group suggest mortality higher than that of the general population with
      deaths attributed mainly to circulatory, respiratory and infectious causes. Women
      seem to have higher mortality ratios, and assessment of time trends suggests
      improvement over the years. There is no consensus on predictive factors of
      mortality but those most consistently identified are older age at diagnosis and
      high doses of glucocorticoid substitution therapy. Well designed and of adequate
      power studies are needed to establish the significance of factors compromising
      the survival of patients with NFA and to facilitate improvements in long-term
      prognosis.

PMID- 29344907
TI  - Silent corticotroph adenomas.
AB  - PURPOSE: Silent corticotroph adenomas (SCAs) present clinically as non
      functioning adenomas (NFAs) but are immunopositive for adrenocorticotrophic
      hormone (ACTH) without biochemical and clinical manifestation of
      hypercortisolism. Pathologic examination of resected NFAs that demonstrate
      positive ACTH and/or TPIT expression confirms its corticotroph lineage. SCAs
      comprise up to 20% of NFAs and exhibit a higher rate of recurrence. Studies of
      molecular mechanisms have generated multiple hypotheses on SCA tumorigenesis,
      pathophysiology, and growth that as yet remain to be proven. An improved
      understanding of their pathologic and clinical characteristics is needed.
      METHODS: A literature review was performed using PubMed to identify research
      reports and clinical case series on SCAs. RESULTS: Up to date findings regarding
      epidemiology, mechanisms of pathogenesis, differentiation, progression, and
      growth, as well as clinical presentation, postoperative course, and treatment
      options for patients with SCAs are presented. Pooled results demonstrate that 25
      40% of cases show cavernous sinus invasion, preoperative hypopituitarism, new
      onset hypopituitarism, and recurrence. CONCLUSION: This article reviews the
      incidence, molecular pathology, and clinical behavior of these unique non
      functioning pituitary corticotroph adenomas, and highlights the need for rigorous
      monitoring for recurrences and hypopituitarism in patients with SCAs.

PMID- 29344908
TI  - Encoding differences affect the number and precision of own-race versus other
      race faces stored in visual working memory.
AB  - Other-race faces are discriminated and recognized less accurately than own-race
      faces. Despite a wealth of research characterizing this other-race effect (ORE),
      little is known about the nature of the representations of own-race versus other
      race faces. This is because traditional measures of this ORE provide a binary
      measure of discrimination or recognition (correct/incorrect), failing to capture
      potential variation in the quality of face representations. We applied a novel
      continuous-response paradigm to independently measure the number of own-race and
      other-race face representations stored in visual working memory (VWM) and the
      precision with which they are stored. Participants reported target own-race or
      other-race faces on a circular face space that smoothly varied along the
      dimension of identity. Using probabilistic mixture modeling, we found that
      following ample encoding time, the ORE is attributable to differences in the
      probability of a face being maintained in VWM. Reducing encoding time, a
      manipulation that is more sensitive to encoding limitations, caused a loss of
      precision or an increase in variability of VWM for other-race but not own-race
      faces. These results suggest that the ORE is driven by the inefficiency with
      which other-race faces are rapidly encoded in VWM and provide novel insights
      about how perceptual experience influences the representation of own-race and
      other-race faces in VWM.

PMID- 29344909
TI  - Flash-induced forward and reverse illusory line motion in offset bars.
AB  - Illusory line motion (ILM) refers to perception of motion in a bar that onsets or
      offsets all at once. When the bar onsets or offsets between two boxes after one
      of the boxes flashes, the bar appears to shoot out of the flashed box (flashILM).
      If the bar offsets during the flash, it appears to contract into the flashed box
      (reverse ILM; rILM). Onset bars do not show rILM. Moreover, rILM and flashILM are
      not correlated, indicating they are two different illusions. To date, rILM has
      only been studied using a 50-ms flash where the bar offsets 16.7 ms after flash
      onset. It is not clear if rILM is due to the 16.7-ms flash-bar-removal stimulus
      onset asynchrony (SOA) or due to the flash offsetting after the bar. The current
      studies explore these parameters to better understand the conditions that lead to
      rILM. The results suggest that flashILM is sensitive to the temporal interval
      between flash onset and bar offset, while rILM appears to arise when the flash
      offsets after the bar has been removed regardless of the temporal interval
      between flash onset and bar removal. These results are consistent with flashILM
      reflecting visual exogenous attention while rILM may reflect the low-level
      spreading of subthreshold activation radiating from the flashed box. The findings
      are incorporated into the recent work that suggests that the literature
      concerning ILM is possibly conflating a number of different illusions of line
      motion, including polarized gamma motion (PGM), transformational apparent motion
      (TAM), and exogenous attention induced motion (flashILM).

PMID- 29344910
TI  - Mimesis and clinical pictures: thinking with Plato and Broekman through the
      production and meaning of images of disease.
AB  - This paper contends, following Plato and Broekman, that (1) seeing images as
      images is crucial to theorizing medicine and that (2) considering clinical
      pictures as images of images is a much-needed epistemic complement to the
      domineering view that sees clinical pictures as mirrors of disease. This does not
      only offer epistemic, but also ethical benefits to individual patients,
      especially in those cases where patients suffer from chronic, debilitating, and
      terminal illnesses and where medicine provides no, or limited, answers in terms
      of treatment, intervention, and meaning. By creating room for a theory of
      clinical pictures that rightfully emphasizes its pictorial nature, patients and
      doctors alike may be encouraged to consider under what authorship, and with which
      epistemic tools, alternative, supplemental images may be produced to get at the
      existential reality of disease and suffering. Ultimately, this paper argues that
      the epistemic tools provided by aesthetics may offer such glimpses into the
      reality of disease and suffering, and I conclude by discussing a few artistic
      renditions of breast cancer to illustrate my point.

PMID- 29344911
TI  - Recurrent infectious subcapsular renal hematoma accompanied by microaneurysm.
AB  - An 80-year-old woman was admitted to the hospital complaining of loss of
      appetite. 10 days earlier, her oral intake gradually decreased with no other
      specific symptoms, such as abdominal pain, nausea, vomiting, headache, or low
      back pain. Abdominal computed tomography (CT) scan revealed a left subcapsular
      renal hematoma. We suspected infective subcapsular renal hematoma, so
      percutaneous needle aspiration and drainage were performed. Intravenous sulbactam
      ampicillin was started immediately. On day 9 after admission, repeat CT scan
      revealed the subcapsular hematoma had reduced in size. The drain was removed, and
      intravenous antibiotics were discontinued. Follow-up CT scan on day 21 revealed
      increased subcapsular renal hematoma size. The patient also had high fever.
      Suspecting recurrence of infective subcapsular renal hematoma, we repeated the
      drainage of the hematoma and restarted intravenous antibiotics. Renal
      arteriography showed a renal artery microaneurysm and her condition improved with
      renal artery embolization. Renal arteriography was useful for detecting renal
      artery microaneurysm in infective subcapsular renal hematoma that did not resolve
      after antibiotic treatment and drainage.

PMID- 29344912
TI  - Capillary leak syndrome as a complication of antibody-mediated rejection
      treatment: a case report.
AB  - We report a case of capillary leak that developed during treatment of antibody
      mediated rejection in a kidney transplant recipient. A 53-year-old female
      transplant recipient experienced an increase in serum creatinine from 1.1 to 1.8
      mg/dL. Antibody-mediated rejection was diagnosed by graft biopsy. She was treated
      with five plasmapheresis sessions (on alternate days with albumin replacement),
      five doses of immunoglobulin (5 g/dose at 100 mg/kg), a single dose of rituximab
      (500 mg), and four doses of bortezomib on days 1, 4, 7, and 10 (1.72 mg/dose at
      1.3 mg/m2 body surface area). During treatment, edema, slight diarrhea,
      pancytopenia, hypoalbuminemia, peripheral neuropathy, and postural hypotension
      were noted. Despite control of liquids, she presented with edema progressing to
      an increase of more than 10 kg body weight. Prerenal acute graft dysfunction
      associated with hypotension was diagnosed on day 12, heart failure or other
      infectious complications being discounted. On day 13, daily hemodialysis was
      prescribed, and a stable volume status was reached after five hemodialysis
      sessions. On day 20, the patient recovered diuresis and the edema and diarrhea
      abated, but she remained on chronic hemodialysis. After excluding other causes of
      distributive shock, the diagnosis of capillary leak syndrome was based on the
      presence of hypotension, generalized edema, and hypoalbuminemia in the absence of
      significant proteinuria. The concomitant presence of diarrhea, peripheral
      neuropathy, and pancytopenia, suggest a possible causal role for bortezomib.
      Awareness by clinicians of capillary leak syndrome associated with bortezomib
      based treatment of AMR is paramount, despite its rarity.

PMID- 29344913
TI  - Cardiac basal autophagic activity and increased exercise capacity.
AB  - To investigate whether high-intensity interval training (HIIT) and continuous
      moderate-intensity training (CMT) have different impacts on exercise performance
      and cardiac function and to determine the influence of these exercise protocols
      on modulating basal autophagy in the cardiac muscle of rats. Rats were assigned
      to three groups: sedentary control (SC), CMT, and HIIT. Total exercise volume and
      mean intensity were matched between the two protocols. After a 10-week training
      program, rats were evaluated for exercise performance, including exercise
      tolerance and grip strength. Blood lactate levels were measured after an
      incremental exercise test. Cardiac function and morphology were assessed by
      echocardiography. Western blotting was used to evaluate the expression of
      autophagy and mitochondrial markers. Transmission electron microscopy was used to
      evaluate mitochondrial content. The results showed that time to exhaustion and
      grip strength increased significantly in the HIIT group compared with the SC and
      CMT groups. Both training interventions significantly increased time to
      exhaustion, reduced blood lactate level (after an incremental exercise test) and
      induced adaptive changes in cardiac morphology, but without altering cardiac
      systolic function. The greater improvements in exercise performance with the HIIT
      than with the CMT protocol were related to improvement in basal autophagic
      adaptation and mitochondria function in cardiac muscle. Mitochondria markers were
      positively correlated with autophagy makers. This study shows that HIIT is more
      effective for improving exercise performance than CMT and this improvement is
      related to mitochondrial function and basal autophagic adaptation in cardiac
      muscle.

PMID- 29344914
TI  - High lithium tolerance of Apocynum venetum seeds during germination.
AB  - Identification and use of lithium (Li) accumulator plants is a promising strategy
      to remediate Li-contaminated soil. Apocynum venetum is reported as a Li
      accumulator. However, its tolerance to Li salt during germination is still
      unknown. The primary aim of this study was to investigate the effects of two Li
      salts on seed germination of A. venetum. At the same concentrations, germination
      percentages in LiCl solution were higher than that in Li2CO3 solution. At 25 
      degrees C, seeds germinated to 4-90% at 0-400 mmol L-1 LiCl and 3-91% at 0-150
      mmol L-1 Li2CO3. Low concentration (0-50 mmol L-1) of LiCl did not significantly
      affect germination percentage. The simulated critical value (when germination
      percentage is 50%) in LiCl solution is 196 mmol L-1, and 36 mmol L-1 for Li2CO3.
      Activity of alpha-amylase, contents of MDA, soluble sugar, and proline were
      dramatically affected by Li salts, especially at medium and late germination
      stages. When compared with control, alpha-amylase activity of seeds under 25 mmol
      L-1 LiCl and 10 mmol L-1 Li2CO3 did not show significant difference. Germination
      percentage and index, radicle length, and physiological parameters indicate A.
      venetum seeds are highly tolerant to Li salts during germination, especially
      LiCl.

PMID- 29344915
TI  - Mechanistic investigation of visible light driven photocatalytic inactivation of
      E. coli by Ag-AgCl/ZnFe2O4.
AB  - In this study, photocatalytic inactivation of Escherichia coli was investigated
      over magnetic nanocomposite Ag-AgCl/ZnFe2O4. The nanocomposite demonstrated
      efficient photocatalytic activity by complete inactivation of the bacteria within
      60 min of visible light irradiation. The anions HPO42- and SO42- were found to
      play the most important role in the inhibition of photocatalytic inactivation of
      E. coli. A systematic investigation of mechanism of photocatalytic bacterial
      inactivation was carried out based on cell membrane injury test, scanning
      electron microscopy (SEM) of bacterial morphology changes, Fourier transform
      infrared (FTIR) spectroscopy of E. coli cells before and after treatment,
      superoxide dismutase (SOD) and catalase (CAT) activity assay, and role of various
      reactive oxygen species (ROS). The activities of SOD and CAT enzymes were found
      to decrease due to the ROSs attacks during photocatalytic inactivation. The ROS
      produced in the photocatalytic disinfection severely altered the bacterial
      permeability and led to protein fragmentation, release of ions, and generation of
      protein carbonyl derivatives. The leaked cytoplasmic substances and cell debris
      were further degraded and, ultimately, mineralized with prolonged photocatalytic
      treatment.

PMID- 29344917
TI  - Non-cardiac uptake of technetium-99m pyrophosphate in transthyretin cardiac
      amyloidosis.
AB  - BACKGROUND: Technetium-based bone scintigraphy is rapidly becoming the most
      common non-invasive imaging tool in the diagnosis of Transthyretin cardiac
      amyloidosis (ATTR). Skeletal muscle uptake has been described with technetium-99m
      3,3-diphosphono-1,2-propanodicarboxylic acid (TcDPD), and may account for masking
      of bony uptake. We sought to investigate skeletal muscle uptake of technetium-99m
      pyrophosphate (TcPYP) in patients with ATTR. METHODS AND RESULTS: This was a
      retrospective analysis of 57 patients diagnosed with ATTR who underwent TcPYP
      scintigraphy. Cardiac uptake was assessed on whole-body planar imaging using a
      semiquantitative scale (grades 0 to 3) and on single-photon emission computed
      tomography (SPECT) with CT attenuation correction using total myocardial counts
      per voxel after a 3-hour incubation. Skeletal muscle (psoas and biceps),
      vertebral body, LV myocardium, and blood pool mean counts were calculated. In the
      cohort (age 78 +/- 9 years, 77% male, and 30% hereditary ATTR), there was no
      visualized tracer uptake in skeletal muscle or soft tissue on qualitative SPECT
      assessment. Total and blood pool-corrected uptake in the muscle groups were
      significantly less than myocardium and bone (P < 0.001). Blood pool-corrected
      muscle uptake was not associated with semiquantitative grade 3 vs 2 uptake (psoas
      P = 0.66, biceps P = 0.13) or presence of hereditary ATTR (psoas P = 0.43, biceps
      P = 0.69). As bony uptake decreased, there was no corresponding increase in
      skeletal muscle uptake. CONCLUSIONS: In patients with ATTR cardiac amyloidosis,
      skeletal muscle uptake of TcPYP is minimal when assessed by qualitative and
      quantitative metrics, and is not significantly different in patients with grade 2
      vs 3 semiquantitative uptake. The properties of this tracer may be different than
      TcDPD with respect to non-cardiac uptake.

PMID- 29344916
TI  - The acute effects of erythromycin and oxytetracycline on enhanced biological
      phosphorus removal system: shift in bacterial community structure.
AB  - Since extensive application, an increasing amount of antibiotics has been
      released into wastewater treatment plants. In this study, the enhanced biological
      phosphorus removal (EBPR) system was fed with synthetic wastewater containing
      erythromycin (ERY) and oxytetracycline (OTC) for 7 days to evaluate the
      variations of solution ortho-P (SOP), volatile fatty acid (VFA), poly
      bhydroxyalkanoates (PHAs), specific oxygen uptake rater (SOUR), and microbial
      community in the EBPR system. The obtained results showed that the P-removal
      efficiency decreased to 0.0%, and at the end of the experiment, only less than
      20% of the VFA could be consumed. Besides, the variable processes of P and PHAs
      were destroyed. Moreover, to better grasp the inhibitory mechanism of
      antibiotics, microbial community compositions of activated sludge sampled in all
      reactors were investigated by high-throughput sequencing techniques. Results of
      comparative and evolutionary analysis revealed that high concentrations (5 and 10
      mg/L) of ERY and OTC could seriously shift microbial communities, while combined
      antibiotics could induce more. Additionally, Accumulibacter and Competibacter
      were two primary microorganisms at the genus level in the EBPR system.
      Accumulibacter decreased seriously for exposure to antibiotics, while
      Competibacter increased in all experimental reactors especially in combined
      antibiotics reactor.

PMID- 29344918
TI  - Artifact-free quantitative cardiovascular PET/MR imaging: An impossible dream?

PMID- 29344919
TI  - The impact of patient-to-detector distance on LV volumes and TID index on SPECT
      myocardial perfusion imaging: Emphasis on consistent patient-detector positioning
      in stress and rest phases.

PMID- 29344920
TI  - Inflammatory reaction of a pericardial foreign body after cardiac surgery.

PMID- 29344921
TI  - Does simplified quantitative analysis of 18F-FDG PET in cardiac inflammatory
      disease work?

PMID- 29344922
TI  - Impact of renin-angiotensin-aldosterone system polymorphisms on myocardial
      perfusion: Correlations with myocardial single photon emission computed
      tomography-derived parameters.
AB  - BACKGROUND: Renin-angiotensin-aldosterone system (RAAS) has an important role in
      atherosclerosis. We investigated the effects of six RAAS gene polymorphisms on
      myocardial perfusion. METHODS AND RESULTS: We examined 810 patients with known or
      suspected coronary artery disease (CAD) using stress-rest myocardial single
      photon emission computed tomography. Summed stress score (SSS), summed rest score
      (SRS), summed difference score (SDS), transient ischemic dilation (TID), and
      lung/heart ratio (LHR) were recorded. The following gene polymorphisms were
      investigated: angiotensin-converting enzyme (ACE) insertion/deletion (I/D),
      angiotensinogen (AGT) M235T and T174M, angiotensin II type 1 receptor (AT1R)
      A1166C, renin (REN) C5312T, and angiotensin II type 2 receptor (AT2R) C3123A. The
      heterozygotes or homozygotes on ACE D allele were 7.54 times more likely to have
      abnormal SSS, while the AGT (T174M) heterozygotes were 5.19 times more likely to
      have abnormal SSS. The homozygotes of ACE D had significantly higher values on
      TID and LHR, while the AGT (T174M) heterozygotes had higher values on TID. The
      AT1R heterozygotes had greater odds for having SSS >= 3. The patients carried
      AT1R homozygosity of C allele had significantly higher values on TID, while
      heterozygotes of AT1R had significantly higher values on LHR. CONCLUSIONS: Among
      the polymorphisms investigated, ACE D allele had the strongest association with
      abnormal myocardial perfusion.

PMID- 29344923
TI  - Potential effects of low-dose average CT on cardiac implantable electronic
      devices.
AB  - BACKGROUND: Average CT has been shown to be more accurate than conventional
      helical CT in quantitation of the PET data. The risk of CT irradiation of a
      cardiac implantable electronic device (CIED) causing an adverse event is low and
      is generally outweighed by the clinical benefit of a medically indicated
      examination. However, irradiation of CIED over one breath cycle in cine CT scan
      for average CT could impose risks on a patient who is pacing dependent. The
      purpose of this study was to demonstrate that low-dose average CT can be safe for
      CIED. METHODS: A Medtronic CIED of model Protecta VR was submerged in a saline
      bath for a series of 4-s cine CT scans on a GE CT scanner programmed to deliver a
      2-cm-wide radiation at a dose rate of 0.9 to 41.2 mGy/s to the CIED. The number
      of over-sensings was recorded as the interference of radiation to the CIED.
      RESULTS: Dose rates >= 1.9 mGy/s caused over-sensing. The higher the dose rate,
      the more over-sensings there were. The lowest dose rate of 0.9 mGy/s did not
      cause any over-sensing. CONCLUSIONS: Low-dose average CT at 0.9 mGy/s can be safe
      for a CIED patient who is pacing dependent.

PMID- 29344924
TI  - Reliability of the 123I-mIBG heart/mediastinum ratio: Results of a multicenter
      test-retest reproducibility study.
AB  - A quantitative measurement, the Heart-to-Mediastinum (H/M) ratio of counts
      derived from a planar acquisition approximately 4 hours after injection of 123I
      mIBG, is a strong predictor of outcomes in patients with stable class II-III
      heart failure and LVEF <= 35%. This study assessed the test-retest
      reproducibility of the H/M ratio in such patients. 47 subjects with class II-III
      systolic heart failure and LVEF <= 35% were tested at two time intervals
      separated by 5 to 14 days. Subjects were imaged twice on the same camera using
      the same radionuclide dose. Images were sent to a core analysis lab, where three
      nuclear technologists independently determined the H/M ratios. The primary
      endpoint was test-retest H/M ratio reproducibility calculated as the absolute
      difference in mean value determined by the three readers. Mean subject age was 65
      +/- 12 years, 85% were male, and mean BMI was 29 +/- 6 kg/m2. Mean injected
      activity was 10.18 +/- 0.43 mCi for first dose and 10.09 +/- 0.52 mCi for the
      second dose. The mean and SD values for first and repeat studies were almost
      identical: the 95% confidence interval of the mean test-retest difference was
      0.055 to 0.076. Bland-Altman plots showed no systematic effect of the H/M ratio
      on the magnitude of the difference between replicate measurements. Inter-reader
      measurements were nearly identical. There were no serious adverse events despite
      exposure to 123I-mIBG on 2 occasions in a short time period. The Heart-to
      Mediastinum ratio of 123I-mIBG is a consistent and highly reproducible
      measurement in stable Class II to III heart failure patients.

PMID- 29344925
TI  - Translating visual information into action predictions: Statistical learning in
      action and nonaction contexts.
AB  - Humans are sensitive to the statistical regularities in action sequences carried
      out by others. In the present eyetracking study, we investigated whether this
      sensitivity can support the prediction of upcoming actions when observing
      unfamiliar action sequences. In two between-subjects conditions, we examined
      whether observers would be more sensitive to statistical regularities in
      sequences performed by a human agent versus self-propelled 'ghost' events.
      Secondly, we investigated whether regularities are learned better when they are
      associated with contingent effects. Both implicit and explicit measures of
      learning were compared between agent and ghost conditions. Implicit learning was
      measured via predictive eye movements to upcoming actions or events, and explicit
      learning was measured via both uninstructed reproduction of the action sequences
      and verbal reports of the regularities. The findings revealed that participants,
      regardless of condition, readily learned the regularities and made correct
      predictive eye movements to upcoming events during online observation. However,
      different patterns of explicit-learning outcomes emerged following observation:
      Participants were most likely to re-create the sequence regularities and to
      verbally report them when they had observed an actor create a contingent effect.
      These results suggest that the shift from implicit predictions to explicit
      knowledge of what has been learned is facilitated when observers perceive another
      agent's actions and when these actions cause effects. These findings are
      discussed with respect to the potential role of the motor system in modulating
      how statistical regularities are learned and used to modify behavior.

PMID- 29344926
TI  - The Mexican Drug War and Early-Life Health: The Impact of Violent Crime on Birth
      Outcomes.
AB  - This study examines the relationship between exposure to violent crime in utero
      and birth weight using longitudinal data from a household survey conducted in
      Mexico. Controlling for selective migration and fertility, the results suggest
      that early gestational exposure to the recent escalation of the Mexican Drug War
      is associated with a substantial decrease in birth weight. This association is
      especially pronounced among children born to mothers of low socioeconomic status
      and among children born to mothers who score poorly on a mental health index.

PMID- 29344927
TI  - Correction to: Protein Biomarkers and Neuroproteomics Characterization of
      Microvesicles/Exosomes from Human Cerebrospinal Fluid Following Traumatic Brain
      Injury.
AB  - The original version of this article unfortunately contained a typographical
      error on Author's name "Firas Kobessiy". This should be corrected as "Firas
      Kobeissy".

PMID- 29344929
TI  - Pla2g6 Deficiency in Zebrafish Leads to Dopaminergic Cell Death, Axonal
      Degeneration, Increased beta-Synuclein Expression, and Defects in Brain Functions
      and Pathways.
AB  - This study aimed to gain insights into the pathophysiology underlying PLA2G6
      associated neurodegeneration that is implicated in three different neurological
      disorders, suggesting that other, unknown genetic or environmental factors might
      contribute to its wide phenotypic expression. To accomplish this, we
      downregulated the function of pla2g6 in the zebrafish nervous system, performed
      parkinsonism-related phenotypic characterization, and determined the effects of
      gene regulation upon the loss of pla2g6 function by using RNA sequencing and
      downstream analyses. Pla2g6 deficiency resulted in axonal degeneration,
      dopaminergic and motor neuron cell loss, and increased beta-synuclein expression.
      We also observed that many of the identified, differentially expressed genes were
      implicated in other brain disorders, which might explain the variable phenotypic
      expression of pla2g6-associated disease, and found that top enriched canonical
      pathways included those already known or suggested to play a major role in the
      pathogenesis of Parkinson's disease. Our data support that pla2g6 is relevant for
      cranial motor development with significant implications in the pathophysiology
      underlying Parkinson's disease.

PMID- 29344928
TI  - Morphine-Mediated Brain Region-Specific Astrocytosis Involves the ER Stress
      Autophagy Axis.
AB  - A recent study from our lab has revealed a link between morphine-mediated
      autophagy and synaptic impairment. The current study was aimed at investigating
      whether morphine-mediated activation of astrocytes involved the ER
      stress/autophagy axis. Our in vitro findings demonstrated upregulation of GFAP
      indicating astrocyte activation with a concomitant increase in the production of
      proinflammatory cytokines in morphine-exposed human astrocytes. Using both
      pharmacological and gene-silencing approaches, it was demonstrated that morphine
      mediated defective autophagy involved upstream activation of ER stress with
      subsequent downstream astrocyte activation via the MU-opioid receptor (MOR). In
      vivo validation demonstrated preferential activation of ER stress/autophagy axis
      in the areas of the brain not associated with pain such as the basal ganglia,
      frontal cortex, occipital cortex, and the cerebellum of morphine-dependent rhesus
      macaques, and this correlated with increased astrocyte activation and
      neuroinflammation. Interventions aimed at blocking either the MOR or ER stress
      could thus likely be developed as promising therapeutic targets for abrogating
      morphine-mediated astrocytosis.

PMID- 29344930
TI  - Maternal prenatal stress and infant DNA methylation: A systematic review.
AB  - Maternal prenatal stress has been linked to a variety of infant postnatal
      outcomes, partially through alterations in fetal HPA axis functioning; yet the
      underlying pathobiology remains elusive. Current literature posits DNA
      methylation as a candidate mechanism through which maternal prenatal stress can
      influence fetal HPA axis functioning. The goal of this systematic review was to
      summarize the literature examining the associations among maternal prenatal
      stress, DNA methylation of commonly studied HPA axis candidate genes, and infant
      HPA axis functioning. Results from the review provided evidence for a link
      between various maternal prenatal stressors, NR3C1 methylation, and infant stress
      reactivity, but findings among other genes were limited, with mixed results. An
      original study quality review tool revealed that a majority of studies in the
      review are adequate, and emphasizes the need for future research to consider
      study quality when interpreting research findings.

PMID- 29344932
TI  - Mothers' Early Mind-Mindedness Predicts Educational Attainment in Socially and
      Economically Disadvantaged British Children.
AB  - Relations between mothers' mind-mindedness (appropriate and nonattuned mind
      related comments) at 8 months (N = 206), and children's educational attainment at
      ages 7 (n = 158) and 11 (n = 156) were investigated in a British sample.
      Appropriate mind-related comments were positively correlated with reading and
      mathematics performance at both ages but only in the low-socioeconomic status
      (SES) group. Path analyses showed that in the low-SES group, appropriate mind
      related comments directly predicted age-11 reading performance, with age-4 verbal
      ability mediating the relation between appropriate mind-related comments and age
      7 reading. In contrast, maternal sensitivity and infant-mother attachment
      security did not predict children's educational attainment. These findings are
      discussed in terms of genetic and environmental contributions to reading and
      mathematics performance.

PMID- 29344933
TI  - Unexpected terrestrial hand posture diversity in wild mountain gorillas.
AB  - OBJECTIVES: Gorillas, along with chimpanzees and bonobos, are ubiquitously
      described as 'knuckle-walkers.' Consequently, knuckle-walking (KW) has been
      featured pre-eminently in hypotheses of the pre-bipedal locomotor behavior of
      hominins and in the evolution of locomotor behavior in apes. However, anecdotal
      and behavioral accounts suggest that mountain gorillas may utilize a more complex
      repertoire of hand postures, which could alter current interpretations of African
      ape locomotion and its role in the emergence of human bipedalism. Here we
      documented hand postures during terrestrial locomotion in wild mountain gorillas
      to investigate the frequency with which KW and other hand postures are utilized
      in the wild. MATERIALS AND METHODS: Multiple high-speed cameras were used to
      record bouts of terrestrial locomotion of 77 habituated mountain gorillas at
      Bwindi Impenetrable National Park (Uganda) and Volcanoes National Park (Rwanda).
      RESULTS: We captured high-speed video of hand contacts in 8% of the world's
      population of mountain gorillas. Our results reveal that nearly 40% of these
      gorillas used "non-KW" hand postures, and these hand postures constituted 15% of
      all hand contacts. Some of these "non-KW" hand postures have never been
      documented in gorillas, yet match hand postures previously identified in
      orangutans. DISCUSSION: These results highlight a previously unrecognized level
      of hand postural diversity in gorillas, and perhaps great apes generally.
      Although present at lower frequencies than KW, we suggest that the possession of
      multiple, versatile hand postures present in wild mountain gorillas may represent
      a shared feature of the African ape and human clade (or even great ape clade)
      rather than KW per se.

PMID- 29344934
TI  - Clinical impact of treatment delay in pancreatic cancer patients revisited.

PMID- 29344931
TI  - Relationship between body mass, lean mass, fat mass, and limb bone cross
      sectional geometry: Implications for estimating body mass and physique from the
      skeleton.
AB  - OBJECTIVES: Estimating body mass from skeletal dimensions is widely practiced,
      but methods for estimating its components (lean and fat mass) are poorly
      developed. The ability to estimate these characteristics would offer new insights
      into the evolution of body composition and its variation relative to past and
      present health. This study investigates the potential of long bone cross
      sectional properties as predictors of body, lean, and fat mass. MATERIALS AND
      METHODS: Humerus, femur and tibia midshaft cross-sectional properties were
      measured by peripheral quantitative computed tomography in sample of young adult
      women (n = 105) characterized by a range of activity levels. Body composition was
      estimated from bioimpedance analysis. RESULTS: Lean mass correlated most strongly
      with both upper and lower limb bone properties (r values up to 0.74), while fat
      mass showed weak correlations (r <= 0.29). Estimation equations generated from
      tibial midshaft properties indicated that lean mass could be estimated relatively
      reliably, with some improvement using logged data and including bone length in
      the models (minimum standard error of estimate = 8.9%). Body mass prediction was
      less reliable and fat mass only poorly predicted (standard errors of estimate
      >=11.9% and >33%, respectively). DISCUSSION: Lean mass can be predicted more
      reliably than body mass from limb bone cross-sectional properties. The results
      highlight the potential for studying evolutionary trends in lean mass from
      skeletal remains, and have implications for understanding the relationship
      between bone morphology and body mass or composition.

PMID- 29344935
TI  - Progressive topological disorganization of brain network in focal epilepsy.
AB  - OBJECTIVE: Increasing evidence has suggested that epilepsy is a network disease.
      Graph theory is a mathematical tool that allows for the analysis and
      quantification of the brain network. We aimed to evaluate the influences of
      duration of epilepsy on the topological organization of brain network in focal
      epilepsy patients with normal MRI using the graph theoretical analysis based on
      diffusion tenor imaging. METHODS: We prospectively enrolled 66 patients with
      focal epilepsy (18/66 patients were newly diagnosed) and 84 healthy subjects. All
      of the patients with epilepsy had normal MRI on visual inspection. All of the
      subjects underwent diffusion tensor imaging that was analyzed using graph theory
      to obtain network measures. RESULTS: The measures of characteristic path length
      and small-worldness in the patients with focal epilepsy were significantly
      decreased, even after multiple corrections (P < .01). Moreover, the measures
      including mean clustering coefficient and global efficiency in the patients with
      epilepsy had strong tendency to decrease compared to those in healthy subjects (P
      = .0153 and P = .0138, respectively). When comparing the measures among the
      patients with newly diagnosed/chronic epilepsy and healthy subjects using ANOVA,
      the characteristic path length (P = .006), small-worldness (P = .032), and global
      efficiency (P = .004) were significantly different. In addition, the duration of
      epilepsy was negatively correlated with global efficiency (r = -.249, P = .0454).
      CONCLUSIONS: We newly found a progressive topological disorganization of the
      brain network in focal epilepsy. In addition, we demonstrated disrupted
      topological organization in focal epilepsy, shifting toward a more random state.

PMID- 29344936
TI  - Author's reply to : Pancreatic cancer : Extension of tumor is associated with
      timeliness of care and with survival in a population-based study.

PMID- 29344937
TI  - NDUFAF3 variants that disrupt mitochondrial complex I assembly may associate with
      cavitating leukoencephalopathy.
AB  - Genetic abnormalities in mitochondrial complex assembling factors are associated
      with leukoencephalopathy. We present a 1-year-old girl with consciousness
      disturbance after a respiratory infection. Brain MRI revealed leukoencephalopathy
      with bilaterally symmetrical hyperintensity in the substantia nigra, medial
      thalamic nuclei, and basal nuclei, as well as cavities in the cerebral white
      matter and corpus callosum. Lactate levels in the spinal fluid were high, while
      magnetic resonance spectroscopy of the cerebral white matter and basal nuclei
      showed high peak lactate levels, suggesting mitochondrial dysfunction. The
      respiratory enzyme activity of complex I was reduced to 17% to 21% in skeletal
      muscle. Whole exome sequencing identified compound heterozygous variations in
      NDUFAF3, involved in the assembly of mitochondrial complex I
      (c.342_343insGTG:p.117Valdup, c.505C > A:p.Pro169Thr). Two-dimensional, blue
      native polyacrylamide gel electrophoresis (PAGE) and sodium dodecyl sulfate-PAGE
      revealed reductions in Q-module (NDUFS2, NDUFS3, and NDUFA9) and P-module
      (NDUFB10 and NDUFB11) subunits, indicating disruption of mitochondrial complex I
      assembly. Our report expands the spectrum of clinical phenotypes associated with
      pathogenic variants of NDUFAF3.

PMID- 29344938
TI  - A clinical audit on the efficacy and safety of uterine artery embolisation for
      symptomatic adenomyosis: Results in 117 women.
AB  - BACKGROUND: Uterine artery embolisation (UAE) is a possible uterine-sparing
      treatment option for women with unsuccessful conservative management for
      adenomyosis-related heavy menstrual bleeding (HMB) and dysmenorrhoea. AIM: To
      conduct a clinical audit on the efficacy and safety of UAE for symptomatic
      adenomyosis. MATERIALS AND METHODS: Retrospective review of 309 women who
      underwent UAE identified 117 women with magnetic resonance imaging features of
      adenomyosis (junctional zone thickness >= 12 mm). Overall success and HMB control
      were rated by women. Visual analogue scale (VAS) pain score, Uterine Fibroid
      Symptom and health-related Quality of Life (UFS-QoL) symptoms score and quality
      of life score were also used to measure outcome. RESULTS: One hundred and fifteen
      women (98%) were available for outcome evaluation. The mean follow-up was 22.5
      months. Overall clinical success was achieved in 102/115 (89%) women; HMB control
      was achieved in 91/104 (88%); dysmenorrhea relief was achieved in 94/104 (90%),
      with VAS reduction of 6.13 (P < 0.001), Mean symptoms score was reduced from 58
      to 17 at 12 months (P < 0.001) and QoL score increased from 42 to 88 at 12 months
      (P < 0.001). Hysterectomy was performed on six (5%) women. There were three (3%)
      mild groin haematomatas and three (3%) mild subacute complications (one possible
      endometritis, two urinary tract infections; all responded to oral antibiotics).
      Two women had unintended pregnancies which were complicated. CONCLUSIONS: In this
      clinical audit UAE was found to be an effective uterine-sparing option for women
      who had unsuccessful conservative treatments for adenomyosis-related HMB and
      dysmenorrhoea. There were no major complications. Two women had unintended
      pregnancies that were complicated.

PMID- 29344939
TI  - Socially informed dispersal in a territorial cooperative breeder.
AB  - Dispersal is a key process governing the dynamics of socially and spatially
      structured populations and involves three distinct stages: emigration, transience
      and settlement. At each stage, individuals have to make movement decisions, which
      are influenced by social, environmental and individual factors. Yet, a
      comprehensive understanding of the drivers that influence such decisions is still
      lacking, particularly for the transient stage during which free-living
      individuals are inherently difficult to follow. Social circumstances such as the
      likelihood of encountering conspecifics can be expected to strongly affects
      decision-making during dispersal, particularly in territorial species where
      encounters with resident conspecifics are antagonistic. Here, we analysed the
      movement trajectories of 47 dispersing coalitions of Kalahari meerkats Suricata
      suricatta through a landscape occupied by constantly monitored resident groups,
      while simultaneously taking into account environmental and individual
      characteristics. We used GPS locations collected on resident groups to create a
      georeferenced social landscape representing the likelihood of encountering
      resident groups. We used a step-selection function to infer the effect of social,
      environmental and individual covariates on habitat selection during dispersal.
      Finally, we created a temporal mismatch between the social landscape and the
      dispersal event of interest to identify the temporal scale at which dispersers
      perceive the social landscape. Including information about the social landscape
      considerably improved our representation of the dispersal trajectory compared to
      analyses that only accounted for environmental variables. The latter were only
      marginally selected or avoided by dispersers. Before leaving their natal
      territory, dispersers selected areas frequently used by their natal group. In
      contrast, after leaving their natal territory, they selectively used areas where
      they were less likely to encounter unrelated groups. This pattern was
      particularly marked in larger dispersing coalitions and when unrelated males were
      part of the dispersing coalition. Our results suggest that, in socially and
      spatially structured species, dispersers gather and process social information
      during dispersal, and that reducing risk of aggression from unrelated resident
      groups outweighs benefits derived from conspecific attraction. Finally, our work
      underlines the intimate link between the social structure of a population and
      dispersal, which affect each other reciprocally.

PMID- 29344940
TI  - Obstetric and neonatal outcomes for women intending to use immersion in water for
      labour and birth in Western Australia (2015-2016): A retrospective audit of
      clinical outcomes.
AB  - BACKGROUND: Research supports water immersion for labour if women are healthy,
      with no obstetric or medical risk factors. AIMS: To evaluate the obstetric and
      neonatal outcomes of women intending to use immersion in water for labour or
      birth. METHODS: Retrospective audit of clinical outcomes for women intending to
      labour or birth in water conducted between July 2015 and June 2016, at a tertiary
      maternity hospital in Western Australia. Obstetric and neonatal data were
      collected from medical records. Multivariable logistic regression was utilised to
      investigate women who laboured in water stratified by those who birthed in water.
      RESULTS: A total of 502 women intended to labour or birth in water; 199 (40%) did
      not and 303 (60%) did. The majority of women using water immersion (179 of 303;
      59%) birthed in water. Multiparous women were more likely than primparous to
      birth in water (73% vs 46%; P < 0.001). Women who birthed in water were at
      increased odds of: a first stage labour <=240 min (odds ratio (OR) 2.56, 95% CI
      1.34-4.87, P = 0.004); a second stage <=60 min (OR 3.53, 95% CI 1.82-6.84, P <
      0.000); a third stage labour of 11-30 min (OR 2.15, 95% CI 1.23-3.78, P = 0.008);
      and having an intact perineum (OR 3.10, 95% CI 1.70-5.64, P < 0.000). CONCLUSION:
      Not all women who set out to labour and birth in water achieve their aim. There
      is a need for high-quality collaborative research into this option of labour and
      birth, so women can make an informed choice around this birth option.

PMID- 29344941
TI  - Systemic patterns of trabecular bone across the human and chimpanzee skeleton.
AB  - Aspects of trabecular bone architecture are thought to reflect regional loading
      of the skeleton, and thus differ between primate taxa with different locomotor
      and postural modes. However, there are several systemic factors that affect bone
      structure that could contribute to, or be the primary factor determining,
      interspecific differences in bone structure. These systemic factors include
      differences in genetic regulation, sensitivity to loading, hormone levels, diet,
      and activity levels. Improved understanding of inter-/intraspecific variability,
      and variability across the skeleton of an individual, is required to interpret
      properly potential functional signals present within trabecular structure. Using
      a whole-region method of analysis, we investigated trabecular structure
      throughout the skeleton of humans and chimpanzees. Trabecular bone volume
      fraction (BV/TV), degree of anisotropy (DA) and trabecular thickness (Tb.Th) were
      quantified from high resolution micro-computed tomographic scans of the humeral
      and femoral head, third metacarpal and third metatarsal head, distal tibia, talus
      and first thoracic vertebra. We found that BV/TV is, in most anatomical sites,
      significantly higher in chimpanzees than in humans, suggesting a systemic
      difference in trabecular structure unrelated to local loading regime. Differences
      in BV/TV between the forelimb and hindlimb did not clearly reflect differences in
      locomotor loading in the study taxa. There were no clear systemic differences
      between the taxa in DA and, as such, this parameter might reflect function and
      relate to differences in joint loading. This systemic approach reveals both the
      pattern of variability across the skeleton and between taxa, and helps identify
      those features of trabecular structure that may relate to joint function.

PMID- 29344942
TI  - Maternal care affects chicks' development differently according to sex in quail.
AB  - Maternal behavior is known to influence the behavioral development of young.
      Recently, it was demonstrated that maternal behavior also differed according to
      sex chicks and brood sex composition. So, here, we explored if these factors
      influenced behavioral development of chicks quail when they were brooded, and
      what characteristics of chicks and foster females could best explain this
      development. We studied three sets of chick pairs brooded by foster females:
      unisex male, unisex female, and mixed broods. We found that both emotivity
      profile and sociality depended on the sex: females were more reactive and less
      social than males. Females' emotivity profile was correlated with brood
      composition and foster female activity during maternal care. In males, only
      sociality was correlated with foster females' scores of aggressive rejection. Our
      results evidence that male and female chicks respond differentially to maternal
      behavior. This is discussed in terms of ecological and physiological constraints
      on development according to sex.

PMID- 29344943
TI  - An exploratory analysis of the joint contribution of HPA axis activation and
      motivation to early adolescent depressive symptoms.
AB  - This study examines the interactive contribution of the hypothalamic-pituitary
      adrenal (HPA) axis and approach-avoidance motivation systems to longitudinal
      changes in depressive symptoms across the adolescent transition. In the summer
      prior to, or fall of, 4th grade, 132 youth (68 girls; 64 boys; M age = 9.46
      years) participated in a social challenge task and reported on their depressive
      symptoms. In the winter of 6th grade, youth completed a semi-structured interview
      of depression and a self-report measure of approach-avoidance motivations.
      Analyses revealed two profiles of risk for adolescent depressive symptoms, with
      some gender differences: (1) excessive disengagement, reflected in HPA
      underactivation along with low approach motivation or high avoidance motivation;
      and (2) excessive engagement, reflected in HPA overactivation along with high
      approach motivation. This research highlights the importance of a multi-system
      perspective on development, suggesting that the implications of HPA dysregulation
      for depressive symptoms are contingent on adolescents' tendencies toward approach
      versus avoidance.

PMID- 29344945
TI  - Cumulative risk exposure moderates the association between parasympathetic
      reactivity and inhibitory control in preschool-age children.
AB  - A child's cumulative risk for early exposure to stress has been linked to
      alterations of self-regulation outcomes, including neurobiological correlates of
      inhibitory control (IC). We examined whether children's ability to engage the
      parasympathetic nervous system impacts how risk affects IC. Children ages 3-5
      years completed two laboratory measures of IC while respiratory sinus arrhythmia
      (RSA) was measured, indexing parasympathetic activity. Children with greater risk
      demonstrated lower IC; risk also moderated associations between RSA reactivity
      and IC. For children with less risk, greater RSA withdrawal during IC tasks was
      associated with better IC. In contrast, greater risk was associated with poor IC,
      regardless of RSA withdrawal. Effects of risk were more pronounced for cumulative
      than individual measures. Results suggest that cumulative risk exposure disrupts
      connectivity between physiological and behavioral components of self-regulation
      in early childhood. Parasympathetic withdrawal to cognitive tasks may be less
      relevant for performance in developmental samples experiencing greater life
      stress.

PMID- 29344944
TI  - Early temperamental fearfulness and the developmental trajectory of error-related
      brain activity.
AB  - The error-related negativity (ERN) is a negative deflection in the event-related
      potential waveform that occurs when an individual makes a mistake, and an
      increased ERN has been proposed as a biomarker for anxiety. However, previous
      work suggests that fearful children are characterized by a smaller ERN. We have
      proposed that this may reflect the changing phenomenology of anxiety across
      development. In the current study, we investigate this possibility using a
      longitudinal within-subject design. In 271 children, we completed observational
      measures of fear when the children were 3 years old, and then measured the ERN
      when the children were 6 and 9 years old. Fearful children were characterized by
      a decreased ERN when they were 6-year-old; by age 9, the same children who were
      fearful at age 3 had increased ERNs-a pattern that closely resembles that of
      anxious adolescents and adults.

PMID- 29344946
TI  - Preeclampsia and scleroderma: a prospective nationwide analysis.
AB  - INTRODUCTION: In a preliminary case-control study, women with scleroderma more
      frequently reported having had hypertensive complications during pregnancy
      compared with healthy women. MATERIAL AND METHODS: To prospectively investigate
      this possible association, we conducted a nation-wide cohort analysis of a major
      hypertensive complication during pregnancy, namely preeclampsia, and later
      scleroderma. Analyses were based on Danish register-based birth and hospital
      contact data on preeclampsia and scleroderma. We followed 778,758 women from time
      of giving birth between 1978 and 2010 to end of follow-up, emigration, death, or
      scleroderma diagnosis, whichever occurred first. The association was evaluated by
      incidence rate ratios, obtained in Poisson regression models. RESULTS: We report
      that preeclampsia is associated with a 69% significantly increased risk of later
      developing scleroderma. CONCLUSIONS: Though these findings do not impact clinical
      care directly, the association of preeclampsia with scleroderma underscores the
      significant relation of preeclampsia and other adverse pregnancy outcomes with
      later disease in women and should be included in patient counseling and
      education.

PMID- 29344947
TI  - Genome-wide population structure and admixture analysis reveals weak
      differentiation among Ugandan goat breeds.
AB  - Uganda has a large population of goats, predominantly from indigenous breeds
      reared in diverse production systems, whose existence is threatened by
      crossbreeding with exotic Boer goats. Knowledge about the genetic characteristics
      and relationships among these Ugandan goat breeds and the potential admixture
      with Boer goats is still limited. Using a medium-density single nucleotide
      polymorphism (SNP) panel, we assessed the genetic diversity, population structure
      and admixture in six goat breeds in Uganda: Boer, Karamojong, Kigezi, Mubende,
      Small East African and Sebei. All the animals had genotypes for about 46 105 SNPs
      after quality control. We found high proportions of polymorphic SNPs ranging from
      0.885 (Kigezi) to 0.928 (Sebei). The overall mean observed (HO ) and expected (HE
      ) heterozygosity across breeds was 0.355 +/- 0.147 and 0.384 +/- 0.143
      respectively. Principal components, genetic distances and admixture analyses
      revealed weak population sub-structuring among the breeds. Principal components
      separated Kigezi and weakly Small East African from other indigenous goats. Sebei
      and Karamojong were tightly entangled together, whereas Mubende occupied a more
      central position with high admixture from all other local breeds. The Boer breed
      showed a unique cluster from the Ugandan indigenous goat breeds. The results
      reflect common ancestry but also some level of geographical differentiation.
      admixture and f4 statistics revealed gene flow from Boer and varying levels of
      genetic admixture among the breeds. Generally, moderate to high levels of genetic
      variability were observed. Our findings provide useful insights into maintaining
      genetic diversity and designing appropriate breeding programs to exploit within
      breed diversity and heterozygote advantage in crossbreeding schemes.

PMID- 29344948
TI  - Glycation of ovalbumin after high-intensity ultrasound pretreatment: effects on
      conformation, immunoglobulin (Ig)G/IgE binding ability and antioxidant activity.
AB  - BACKGROUND: Ovalbumin (OVA), a protein with excellent nutritional and processing
      properties, is the major allergen of hen egg white. High-intensity ultrasound
      treatment increases the immunoglobulin (Ig)G and IgE binding abilities by
      unfolding the conformational structure of OVA. This may allow a modification of
      the IgG and IgE binding of OVA by combining high-intensity ultrasound with other
      methods, such as glycation, thus representing a promising method for the
      improvement of protein properties. RESULTS: Glycation with mannose (M) after
      ultrasound pretreatment at 0-600 W significantly reduced the IgG and IgE binding
      abilities and dramatically enhanced the antioxidant activity of OVA-M conjugates,
      with the lowest values of IgG and IgE binding and highest values of antioxidant
      capacity observed at 600 W. Polyacrylamide gel electrophoresis showed that the
      molecular weight of OVA-M conjugates with ultrasound pretreatment increased more
      than non-pretreatment sample, implying that ultrasound pretreatment promoted
      glycation. The alpha-helix content and ultraviolet absorption of OVA were
      observably increased, whereas beta-sheet content, intrinsic fluorescence and
      surface hydrophobicity were notably decreased, indicating that the tertiary and
      secondary structures of OVA were markedly changed. CONCLUSION: High-intensity
      ultrasound pretreatment can be conducive to reducing the binding abilities of IgG
      and IgE and enhancing the antioxidant activity of OVA-M conjugates. Therefore,
      glycation combined with high-intensity ultrasound pretreatment might be a
      promising method for producing hypo-allergenic and high-antioxidant OVA products.
      (c) 2018 Society of Chemical Industry.

PMID- 29344949
TI  - Flavour-active compounds in thermally treated yeast extracts.
AB  - BACKGROUND: Aroma-active compounds and non-volatile substances determine the
      characteristic aroma and taste of yeast extract (YE). Changes in the
      characteristic aroma and taste of YE due to thermal reaction are rarely studied,
      and the relationship between aroma-active compounds and non-volatile compounds is
      not yet clear. RESULTS: Non-volatile compounds identified by HPLC and LC/MS/MS
      were reduced by a rise in temperature, except for some amino acids. Peptides
      underwent degradation. In addition, a further rise in temperature above 120 
      degrees C resulted in a bitter and sour taste. Furans, pyrazines, thiophenes,
      thiazoles and some branched chain sulfur compounds were derived from GC/O/MS
      (SPME and SAFE). Sensory results revealed that the concentration of volatile
      compounds increased with an increase in temperature. The overall aroma profiles
      of YE at 25, 100 and 110  degrees C were buttery, green, nutty and meaty, while
      YE at 140  degrees C had a strong sour and sulfur odour. CONCLUSION: The non
      volatile compounds of YE were reduced and different volatile compounds were
      produced under different thermal treatments. There was a negative correlation
      between these two types of compounds. The different taste sensors and all
      precursors were correlated with each other. There are significant relationships
      between different odorants and aroma-active compounds of YE after thermal
      treatment. (c) 2018 Society of Chemical Industry.

PMID- 29344950
TI  - Systematic review and meta-analysis of left ventricular endocardial pacing in
      advanced heart failure: Clinically efficacious but at what cost?
AB  - INTRODUCTION: Cardiac resynchronization using a left ventricular (LV) epicardial
      lead placed in the coronary sinus is now routinely used in the management of
      heart failure patients. LV endocardial pacing is an alternative when this is not
      feasible, with outcomes data sparse. OBJECTIVE: To review the available evidence
      on the efficacy and safety of endocardial LV pacing via meta-analysis. METHODS:
      EMBASE, MEDLINE, and COCHRANE databases with the search term "endocardial
      biventricular pacing" or "endocardial cardiac resynchronization" or "left
      ventricular endocardial" or "endocardial left ventricular." Comparisons of pre
      and post-QRS width, LV ejection fraction (LVEF), and New York Heart Association
      (NYHA) functional classification was performed, and mean differences (and
      respective 95% confidence interval [CI]) applied as a measurement of treatment
      effect. RESULTS: Fifteen studies, including 362 patients, were selected. During a
      mean follow-up of 40 +/- 24.5 months, death occurred in 72 patients (11 per 100
      patient-years). Significant improvements in LVEF (mean difference 7.9%, 95% CI 5
      10%, P < 0.0001; I2  = 73%), QRS width (mean difference: -41% 95% -75 to -7%; P <
      0.0001; I2  = 94%), and NYHA class (mean difference: -1.06, 95% CI -1.2 to -0.9,
      P < 0.0001; I2  = 60%), (all P < 0.0001) occurred. Stroke rate was 3.3-4.2 per
      100 patient-years, which is higher than equivalent heart failure trial
      populations and recent meta-analysis that included small case series. CONCLUSION:
      LV endocardial lead implantation is a potentially efficacious alternative to CS
      lead placement, but preliminary data suggest a potentially higher risk of stroke
      during follow-up when compared to the expected incidence of stroke in similar
      cohorts of patients.

PMID- 29344951
TI  - The rise of a novel classification system for endometrial carcinoma; integration
      of molecular subclasses.
AB  - Endometrial cancer is a clinically heterogeneous disease and it is becoming
      increasingly clear that this heterogeneity may be a function of the diversity of
      the underlying molecular alterations. Recent large-scale genomic studies have
      revealed that endometrial cancer can be divided into at least four distinct
      molecular subtypes, with well-described underlying genomic aberrations. These
      subtypes can be reliably delineated and carry significant prognostic as well as
      predictive information; embracing and incorporating them into clinical practice
      is thus attractive. The road towards the integration of molecular features into
      current classification systems is not without obstacles. Collaborative studies
      engaging research teams from across the world are working to define pragmatic
      assays, improve risk stratification systems by combining molecular features and
      traditional clinicopathological parameters, and determine how molecular
      classification can be optimally utilized to direct patient care. Pathologists and
      clinicians caring for women with endometrial cancer need to engage with and
      understand the possibilities and limitations of this new approach, because
      integration of molecular classification of endometrial cancers is anticipated to
      become an essential part of gynaecological pathology practice. This review will
      describe the challenges in current systems of endometrial carcinoma
      classification, the evolution of new molecular technologies that define
      prognostically distinct molecular subtypes, and potential applications of
      molecular classification as a step towards precision medicine and refining care
      for individuals with the most common gynaecological cancer in the developed
      world. Copyright (c) 2018 Pathological Society of Great Britain and Ireland.
      Published by John Wiley & Sons, Ltd.

PMID- 29344952
TI  - A Weaning Protocol for Venovenous Extracorporeal Membrane Oxygenation With a
      Review of the Literature.
AB  - Several articles have discussed the weaning process for venoarterial
      extracorporeal membrane oxygenation; however, there is no published report to
      outline a standardized approach for weaning a patient from venovenous
      extracorporeal membrane oxygenation (ECMO). This complex process requires an
      organized approach and a thorough understanding of ventilator management and ECMO
      physiology. The purpose of this article is to describe the venovenous ECMO
      weaning protocol used at our institution as well as provide a review of the
      literature.

PMID- 29344953
TI  - Established, emerging and elusive molecular targets in the treatment of lung
      cancer.
AB  - Although histological subtype still underlies tumour classification and
      treatment, the recognition that lung cancer is, largely, a genetic disease has
      prompted a push to reconfigure cancer taxonomies according to molecular criteria.
      In this review, we discuss established (e.g. EGFR, ALK, ROS1, and programmed cell
      death 1/programmed death-ligand 1), emerging (e.g. MET, RET, and NTRK) and
      elusive (e.g. TP53, KRAS, and MYC) molecular targets in the treatment of lung
      cancer. We synthesize a large and rapidly growing body of literature regarding
      the discovery and therapeutic inhibition of these targets in lung cancer.
      Copyright (c) 2018 Pathological Society of Great Britain and Ireland. Published
      by John Wiley & Sons, Ltd.

PMID- 29344955
TI  - Development of an advanced two-dimensional microdosimetric detector based on
      THick Gas Electron Multipliers.
AB  - PURPOSE: The THick Gas Electron Multiplier (THGEM)-based tissue-equivalent
      proportional counter (TEPC) has been proven to be useful for microdosimetry due
      to its flexibility in varying the gaseous sensitive volume and achieving high
      multiplication gain. Aiming at measuring the spatial distribution of radiation
      dose for mixed neutron-gamma fields, an advanced two-dimensional (2D) THGEM-TEPC
      was designed and constructed at McMaster University which will enable us to
      overcome the operational limitation of the classical TEPCs, particularly for high
      dose rate fields. Compared to the traditional TEPCs, anode wire electrodes were
      replaced by a THGEM layer, which not only enhances the gas multiplication gain
      but also offers a flexible and convenient fabrication for building 2D detectors.
      METHOD & MATERIALS: The 2D THGEM TEPC consists of an array of 3 * 3 sensitive
      volumes, equivalent to nine individual TEPCs, each of which has a dimension of 5
      mm diameter and length. Taking the overall cost, size and flexibility into
      account, to process nine detector signals simultaneously, a multi-input digital
      pulse processing system was developed by using modern microcontrollers, each of
      which is coupled with a 12-bit sampling ADC. RESULTS: Using the McMaster
      Tandetron 7 Li(p,n) accelerator neutron source, both fundamental detector
      performance, as well as neutron dosimetric response of the 2D THGEM-TEPC, has
      been extensively investigated and compared to the data acquired by a standard
      spherical TEPC. It was shown that the microdosimetric response and the measured
      absorbed dose rate of the 2D THGEM detector developed in this study are
      comparable to the standard 1/2" TEPC which is commercially available. CONCLUSION:
      This study proved that the 2D TEPC based on the THGEM technology can be
      effectively used in microdosimetry studies and is a promising detector for
      measuring the absorbed dose rate distribution over an area in mixed radiation
      fields. This unique small gas cavity detector opens new possibilities in
      applications for high-intensity mixed radiation fields as well as in
      nanodosimetry.

PMID- 29344954
TI  - Mixed ductal-lobular carcinomas: evidence for progression from ductal to lobular
      morphology.
AB  - Mixed ductal-lobular carcinomas (MDLs) show both ductal and lobular morphology,
      and constitute an archetypal example of intratumoural morphological
      heterogeneity. The mechanisms underlying the coexistence of these different
      morphological entities are poorly understood, although theories include that
      these components either represent 'collision' of independent tumours or evolve
      from a common ancestor. We performed comprehensive clinicopathological analysis
      of a cohort of 82 MDLs, and found that: (1) MDLs more frequently coexist with
      ductal carcinoma in situ (DCIS) than with lobular carcinoma in situ (LCIS); (2)
      the E-cadherin-catenin complex was normal in the ductal component in 77.6% of
      tumours; and (3) in the lobular component, E-cadherin was almost always
      aberrantly located in the cytoplasm, in contrast to invasive lobular carcinoma
      (ILC), where E-cadherin is typically absent. Comparative genomic hybridization
      and multiregion whole exome sequencing of four representative cases revealed that
      all morphologically distinct components within an individual case were clonally
      related. The mutations identified varied between cases; those associated with a
      common clonal ancestry included BRCA2, TBX3, and TP53, whereas those associated
      with clonal divergence included CDH1 and ESR1. Together, these data support a
      model in which separate morphological components of MDLs arise from a common
      ancestor, and lobular morphology can arise via a ductal pathway of tumour
      progression. In MDLs that present with LCIS and DCIS, the clonal divergence
      probably occurs early, and is frequently associated with complete loss of E
      cadherin expression, as in ILC, whereas, in the majority of MDLs, which present
      with DCIS but not LCIS, direct clonal divergence from the ductal to the lobular
      phenotype occurs late in tumour evolution, and is associated with aberrant
      expression of E-cadherin. The mechanisms driving the phenotypic change may
      involve E-cadherin-catenin complex deregulation, but are yet to be fully
      elucidated, as there is significant intertumoural heterogeneity, and each case
      may have a unique molecular mechanism. (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- 29344956
TI  - Dispersal capacity of Haematopota spp. and Stomoxys calcitrans using a mark
      release-recapture approach in Belgium.
AB  - The dispersion potential of mechanical vectors is an important factor in the
      dissemination of pathogens. A mark-release-recapture experiment was implemented
      using two groups (unfed and partially fed) of the Tabanidae (Diptera)
      (Haematopota spp.) and biting Muscidae (Diptera) (Stomoxys calcitrans) most
      frequently collected in Belgium in order to evaluate their dispersion potential.
      In total, 2104 specimens of Haematopota spp. were collected directly from horses
      and 5396 S. calcitrans were collected in a cattle farm using hand-nets. Some of
      these insects were partially fed in vitro and all were subsequently coloured.
      Overall, 67 specimens of S. calcitrans (1.2%) and 17 of Haematopota spp. (0.8%)
      were recaptured directly on horses. Stomoxys calcitrans flew maximum distances of
      150 m and 300 m when partially fed and unfed, respectively. Haematopota spp.
      travelled maximum distances of 100 m and 200 m when partially fed and unfed,
      respectively. Segregation measures seem essential in order to reduce the risk for
      pathogen transmission. A distance of 150 m appears to be the minimum required for
      segregation to avoid the risk for mechanical transmission, but in areas of higher
      vector density, this should probably be increased.

PMID- 29344957
TI  - Rapid differentiation of Chinese hop varieties (Humulus lupulus) using volatile
      fingerprinting by HS-SPME-GC-MS combined with multivariate statistical analysis.
AB  - BACKGROUND: Hops impart flavor to beer, with the volatile components
      characterizing the various hop varieties and qualities. Fingerprinting,
      especially flavor fingerprinting, is often used to identify 'flavor products'
      because inconsistencies in the description of flavor may lead to an incorrect
      definition of beer quality. Compared to flavor fingerprinting, volatile
      fingerprinting is simpler and easier. RESULTS: We performed volatile
      fingerprinting using head space-solid phase micro-extraction gas chromatography
      mass spectrometry combined with similarity analysis and principal component
      analysis (PCA) for evaluating and distinguishing between three major Chinese
      hops. Eighty-four volatiles were identified, which were classified into seven
      categories. Volatile fingerprinting based on similarity analysis did not yield
      any obvious result. By contrast, hop varieties and qualities were identified
      using volatile fingerprinting based on PCA. The potential variables explained the
      variance in the three hop varieties. In addition, the dendrogram and principal
      component score plot described the differences and classifications of hops.
      CONCLUSION: Volatile fingerprinting plus multivariate statistical analysis can
      rapidly differentiate between the different varieties and qualities of the three
      major Chinese hops. Furthermore, this method can be used as a reference in other
      fields. (c) 2018 Society of Chemical Industry.

PMID- 29344958
TI  - Protective effects of new antioxidant compositions of 4-methylcoumarins and
      related compounds with dl-alpha-tocopherol and l-ascorbic acid.
AB  - BACKGROUND: Coumarin derivatives possess a wide range of biological activities.
      By functionalization of the parent coumarin skeleton that has neither antioxidant
      nor biological activity, a series of new bio-antioxidants has been designed.
      RESULTS: New antioxidant compositions (equimolar binary and ternary mixtures) of
      eight 4-methylcoumarins and three related compounds have been tested and
      different effects between individual components have been observed: synergism
      (positive effect), additivism (summary effect) and antagonism (negative effect).
      Higher oxidative stability of the lipid substrate was obtained in the presence of
      the new antioxidant compositions of the studied compounds with dl-alpha
      tocopherol and l-ascorbic acid. The role of each component in the antioxidant
      compositions of ternary mixtures has been identified by using new equations
      composed by the authors. CONCLUSION: All ternary mixtures demonstrate synergism
      as a result of continuous regeneration of dl-alpha-tocopherol from the studied
      antioxidants and l-ascorbic acid. Theoretical calculations have been probed as
      indicators of the expected effects between the individual components in a binary
      mixture. (c) 2018 Society of Chemical Industry.

PMID- 29344959
TI  - Three gene phylogeny of the Thoreales (Rhodophyta) reveals high species
      diversity.
AB  - The freshwater red algal order Thoreales has triphasic life history composed of a
      diminutive diploid "Chantransia" stage, a distinctive macroscopic gametophyte
      with multi-axial growth and carposporophytes that develop on the gametophyte
      thallus. This order is comprised of two genera, Thorea and Nemalionopsis. Thorea
      has been widely reported with numerous species, whereas Nemalionopsis has been
      more rarely observed with only a few species described. DNA sequences from three
      loci (rbcL, cox1, and LSU) were used to examine the phylogenetic affinity of
      specimens collected from geographically distant locations including North
      America, South America, Europe, Pacific Islands, Southeast Asia, China, and
      India. Sixteen species of Thorea and two species of Nemalionopsis were
      recognized. Morphological observations confirmed the distinctness of the two
      genera and also provided some characters to distinguish species. However, many of
      the collections were in "Chantransia" stage rather than gametophyte stage,
      meaning that key diagnostic morphological characters were unavailable. Three new
      species are proposed primarily based on the DNA sequence data generated in this
      study, Thorea kokosinga-pueschelii, T. mauitukitukii, and T. quisqueyana. In
      addition to these newly described species, one DNA sequence from GenBank was not
      closely associated with other Thorea clades and may represent further diversity
      in the genus. Two species in Nemalionopsis are recognized, N. shawii and N.
      parkeri nom. et stat. nov. Thorea harbors more diversity than had been recognized
      by morphological data alone. Distribution data indicated that Nemalionopsis is
      common in the Pacific region, whereas Thorea is more globally distributed. Most
      species of Thorea have a regional distribution, but Thorea hispida appears to be
      cosmopolitan.

PMID- 29344960
TI  - Association of genetic variation in telomere-related SNP and telomerase with
      ventricular arrhythmias in ischemic cardiomyopathy.
AB  - BACKGROUND: Telomeres are known to provide genomic stability and telomere length
      has been associated with cardiovascular diseases. Moreover, a higher telomerase
      activity has been shown to be associated with ventricular arrhythmias (VA) in
      ischemic cardiomyopathy. Increasing evidence suggests that genetic variation in
      key telomere genes has an impact on telomerase activity. Each copy of the minor
      allele of SNP rs12696304, at a locus including TERC (telomerase), has been
      associated with ~75 base pairs reduction in mean telomere length likely mediated
      by an effect on TERC expression. We investigated the impact of genetic variation
      of this SNP on telomerase and its association with VA in ischemic cardiomyopathy
      patients. METHODS AND RESULTS: Ninety ischemic cardiomyopathy patients with
      primary prevention implantable cardioverter defibrillators (ICDs) were recruited.
      Thirty-five received appropriate ICD therapy for potentially fatal VA (cases),
      while the remaining 55 patients did not (controls). No significant differences in
      baseline demographics were seen between the groups. TS was measured by qPCR,
      telomerase activity by TRAP assay, and SNP genotyping with Taqman probes.
      Telomerase was highest in C homozygous allele and had a significant association
      with VA in this group only (C/C,C/G,G/G; P-value 0.04, 0.33, 0.43). CONCLUSION:
      The present study is the first to examine the association between telomerase, a
      SNP at a locus including TERC, and VA in ischemic cardiomyopathy patients.
      Homozygosity for C-allele significantly effects telomerase expression and its
      association with VA in this cohort. Large-scale prospective studies are required
      to determine if this genetic variation predisposes patients to greater arrhythmic
      tendency post-MI.

PMID- 29344961
TI  - In vivo evaluation of some biophysical parameters of the facial skin of Indian
      subjects living in Mumbai. Part II: Variability with age and gender.
AB  - BACKGROUND: A previously published work explored the diversity of some
      biophysical parameters (colour, elasticity, sebum production, skin microrelief,
      etc.) of the skin of 1204 Indian women, differently aged, living in four Indian
      cities (Chennai, Delhi, Kolkata and Mumbai). The present work aimed at completing
      such research by focusing on possible gender-related differences in the same skin
      parameters, between Indian men and women living in the same Indian city (Mumbai).
      METHODS: A total of 297 Indian men, differently aged (18-70y), were recruited in
      Mumbai, completing the panel of 303 women who were previously recruited in this
      same city. The same instrumental measurements of facial skin colour and its
      homogeneity, its mechanical properties, the sebum production, skin pores size,
      skin relief, etc. as in the previous work, were conducted. RESULTS: Overall, the
      facial skin colour shows a darker complexion in men as compared to women, on
      forehead, ocular region, lips, chin and cheek. The skin colour unevenness, which
      increases with age, was found higher in men, as compared to women. At comparable
      age, women and men present a same density of skin pores, whereas those of men
      appear larger, up to 55y. The deepness of Crow's feet wrinkles does not
      significantly differ between genders. A lesser extensibility was found on the
      cheeks of men. In men, the sebum production was found significantly higher than
      that of women at ages above 40y. CONCLUSIONS: This work indicates some commonly
      shared age-related skin features between women and men from Mumbai, despite
      slight different characteristics such as skin pigmentation, forehead/cheek colour
      contrast, mechanical properties and sebum production.

PMID- 29344962
TI  - Bridging the molecular divide: alcohol-induced downregulation of PAX9 and tumour
      development.
AB  - The pathogenesis of oro-oesophaeal squamous cell carcinoma is causally linked to
      the consumption of alcohol. Beyond the carcinogenic effects of ethanol and its
      metabolites via DNA damage, the precise mechanisms by which alcohol drives
      tumourigenesis remain to be fully elucidated. A novel contributor now revealed is
      aberrant differentiation and proliferation mediated by suppression of PAX9, a key
      regulator of normal squamous maturation in oro-oesophageal tissues. Copyright (c)
      2018 Pathological Society of Great Britain and Ireland. Published by John Wiley &
      Sons, Ltd.

PMID- 29344963
TI  - Refractory Pulmonary Edema and Upper Body Hypoxemia During Veno-Arterial
      Extracorporeal Membrane Oxygenation-A Case for Atrial Septostomy.
AB  - Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) provides mechanical
      circulatory support for patients with advanced cardiogenic shock, facilitating
      myocardial recovery and limiting multi-organ failure. In patients with severely
      limited left ventricular ejection, peripheral VA-ECMO can further increase left
      ventricular and left atrial pressures (LAP). Failure to decompress the left heart
      under these circumstances can result in pulmonary edema and upper body hypoxemia,
      that is, myocardial and cerebral ischemia. Atrial septostomy can decrease LAP in
      these situations. However, the effects of atrial septostomy on upper body
      oxygenation remain unknown. After IRB approval, we identified 9 out of 242 adult
      VA-ECMO patients between January 2011 and June 2016 who also underwent atrial
      septostomy for refractory pulmonary edema/upper body hypoxemia. We analyzed
      LAP/pulmonary capillary wedge pressure (PCWP), right atrial pressures (RAPs), Pa
      O2 /Fi O2 ratios (blood samples from right radial artery), intrathoracic volume
      status, and resolution of pulmonary edema before and up to 48 h after septostomy.
      There were no procedure-related complications. Thirty-day survival was 44%.
      LAP/PCWP decreased by approximately 40% immediately following septostomy and
      remained so for at least 24 h. Pa O2 /Fi O2 ratios significantly increased from
      0.49 (0.38-2.12) before to 5.35 (3.01-7.69) immediately after septostomy and
      continued so for 24 h, 6.6 (4.49-10.93). Radiographic measurements also indicated
      a significant improvement in thoracic intravascular volume status after atrial
      septostomy. Atrial septostomy reduces LAP and improves upper body oxygenation and
      intrathoracic vascular volume status in patients developing severe refractory
      pulmonary edema while undergoing peripheral VA-ECMO. Atrial septostomy therefore
      appears safe and suitable to reduce the risk of upper body ischemia under these
      circumstances.

PMID- 29344964
TI  - Recent advances and opportunities in proteomic analyses of tumour heterogeneity.
AB  - Solid tumour malignancies comprise a highly variable admixture of tumour and non
      tumour cellular populations, forming a complex cellular ecosystem and tumour
      microenvironment. This tumour heterogeneity is not incidental, and is known to
      correlate with poor patient prognosis for many cancer types. Indeed, non
      malignant cell populations, such as vascular endothelial and immune cells, are
      known to play key roles supporting and, in some cases, driving aggressive tumour
      biology, and represent targets of emerging therapeutics, such as antiangiogenesis
      and immune checkpoint inhibitors. The biochemical interplay between these
      cellular populations and how they contribute to molecular tumour heterogeneity
      remains enigmatic, particularly from the perspective of the tumour proteome. This
      review focuses on recent advances in proteomic methods, namely imaging mass
      spectrometry, single-cell proteomic techniques, and preanalytical sample
      processing, that are uniquely positioned to enable detailed analysis of discrete
      cellular populations within tumours to improve our understanding of tumour
      proteomic heterogeneity. This review further emphasizes the opportunity afforded
      by the application of these techniques to the analysis of tumour heterogeneity in
      formalin-fixed paraffin-embedded archival tumour tissues, as these represent an
      invaluable resource for retrospective analyses that is now routinely accessible,
      owing to recent technological and methodological advances in tumour tissue
      proteomics. Copyright (c) 2018 Pathological Society of Great Britain and Ireland.
      Published by John Wiley & Sons, Ltd.

PMID- 29344965
TI  - Occupational therapy publications by Australian authors: A bibliometric analysis.
AB  - BACKGROUND: Bibliometrics refers to the collection and measurement of publishing
      and citation data configurations with the goal of quantifying the influence of
      scholarly activities. Advantages of bibliometrics include the generation of
      quantitative indicators of impact, productivity, quality and collaboration. Those
      parties who benefit from the results of bibliometric analysis include
      researchers, educators, journal publishers, employers and research funding
      bodies. METHODS: A bibliometric analysis was completed of peer-reviewed
      literature from 1991 to 2015, written by Australian occupational therapists (who
      were able to be identified as such), and indexed in the Science Citation Index
      Expanded (SCI-Expanded) or the Social Sciences Citation Index (SSCI) databases.
      "Occupational therapy" and "occupational therapist(s)" were used as keywords to
      search journal articles' publication title, abstract, author details, keywords
      and KeyWord Plus. RESULTS: Between 1991 and 2015, 752 peer-reviewed journal
      articles were published by Australian occupational therapy authors. On average,
      those articles had 3.7 authors, 35 references, and were nine pages in length. The
      top four journals in which Australian occupational therapists published were
      Australian Occupational Therapy Journal, British Journal of Occupational Therapy,
      American Journal of Occupational Therapy, and Physical and Occupational Therapy
      in Paediatrics. The four Australian institutions that generated the largest
      number of occupational therapy articles were the University of Queensland,
      University of Sydney, La Trobe University, and Monash University. The top four
      countries with whom Australian authors collaborated in manuscript writing were
      the United Kingdom, United States, Canada and Sweden. CONCLUSION: The volume of
      occupational therapy peer-reviewed literature has grown over the last two
      decades. Australian authors have and continue to make significant contributions
      to the occupational therapy body of knowledge nationally and internationally.

PMID- 29344966
TI  - Quorum-sensing molecule dihydroxy-2,3-pentanedione and its analogs as regulators
      of epithelial integrity.
AB  - BACKGROUND AND OBJECTIVE: Quorum-sensing molecules regulate the behavior of
      bacteria within biofilms and at the same time elicit an immune response in host
      tissues. Our aim was to investigate the regulatory role of dihydroxy-2,3
      pentanedione (DPD), the precursor of universal autoinducer-2 (AI-2), and its
      analogs (ethyl-DPD, butyl-DPD and isobutyl-DPD) in the integrity of gingival
      epithelial cells. MATERIAL AND METHODS: Human gingival keratinocytes were
      incubated with four concentrations (10 MUmol L-1 , 1 MUmol L-1 , 100 nmol L-1 and
      10 nmol L-1 ) of DPD and its analogs for 24 hours. The numbers of viable cells
      were determined using a proliferation kit, matrix metalloproteinase (MMP)-2 and 
      9 activities were determined by gelatin zymography, and expression of occludin
      protein and occludin mRNA were determined by western blotting and RT-qPCR,
      respectively. RESULTS: Increased cell proliferation was observed in gingival
      keratinocytes incubated with 100 nmol L-1 of butyl-DPD. MMP-9 activity was
      elevated in cells incubated with 10 MUmol L-1 of ethyl-DPD. On the other hand,
      MMP-2 activity did not show any significant change when gingival keratinocytes
      were incubated with or without DPD or analogs. Western blot analyses demonstrated
      five forms (105, 61, 52.2, 44 and 37 kDa) of occludin. Incubation with 1 MUmol L
      1 and 100 nmol L-1 of DPD and with 10 nmol L-1 of ethyl-DPD increased dimeric
      (105 kDa) forms of occludin, while incubation with 100 nmol L-1 of isobutyl-DPD
      increased monomeric (61 kDa) forms. DPD and ethyl-DPD decreased, and 100 nmol L-1
      of isobutyl-DPD and 10 nmol L-1 of butyl-DPD increased, the monomeric (52.2 kDa
      and 44 kDa) forms of occludin, whereas ethyl-DPD decreased and isobutyl-DPD
      increased, the low-molecular-weight (37 kDa) forms. According to RT-qPCR
      analysis, the exposure of gingival keratinocytes to 10 MUmol L-1 of isobutyl-DPD
      up-regulated expression of occludin. CONCLUSION: The results indicate that
      isobutyl-DPD has the potential to enhance the integrity of the epithelium by
      stimulating the formation of occluding, without affecting the proliferation or
      gelatinolytic enzyme activities of the exposed cells. The modulatory effect of an
      AI-2 analog on the epithelial cell response is shown for the first time.

PMID- 29344967
TI  - Predictive neuromechanical simulations indicate why walking performance declines
      with ageing.
AB  - KEY POINTS: Although the natural decline in walking performance with ageing
      affects the quality of life of a growing elderly population, its physiological
      origins remain unknown. By using predictive neuromechanical simulations of human
      walking with age-related neuro-musculo-skeletal changes, we find evidence that
      the loss of muscle strength and muscle contraction speed dominantly contribute to
      the reduced walking economy and speed. The findings imply that focusing on
      recovering these muscular changes may be the only effective way to improve
      performance in elderly walking. More generally, the work is of interest for
      investigating the physiological causes of altered gait due to age, injury and
      disorders. ABSTRACT: Healthy elderly people walk slower and energetically less
      efficiently than young adults. This decline in walking performance lowers the
      quality of life for a growing ageing population, and understanding its
      physiological origin is critical for devising interventions that can delay or
      revert it. However, the origin of the decline in walking performance remains
      unknown, as ageing produces a range of physiological changes whose individual
      effects on gait are difficult to separate in experiments with human subjects.
      Here we use a predictive neuromechanical model to separately address the effects
      of common age-related changes to the skeletal, muscular and nervous systems. We
      find in computer simulations of this model that the combined changes produce gait
      consistent with elderly walking and that mainly the loss of muscle strength and
      mass reduces energy efficiency. In addition, we find that the slower preferred
      walking speed of elderly people emerges in the simulations when adapting to
      muscle fatigue, again mainly caused by muscle-related changes. The results
      suggest that a focus on recovering these muscular changes may be the only
      effective way to improve performance in elderly walking.

PMID- 29344968
TI  - A novel nested polymerase chain reaction assay targeting Plasmodium mitochondrial
      DNA in field-collected Anopheles mosquitoes.
AB  - Sensitive techniques for the detection of Plasmodium (Aconoidasida: Plasmodiidae)
      sporozoites in field-collected malaria vectors are essential for the correct
      assessment of risk for malaria transmission. A real-time polymerase chain
      reaction (RT-PCR) protocol targeting Plasmodium mtDNA proved to be much more
      sensitive in detecting sporozoites in mosquitoes than the widely used enzyme
      linked immunosorbent assay targeting Plasmodium circumsporozoite protein (CSP
      ELISA). However, because of the relatively high costs associated with equipment
      and reagents, RT-PCRs are mostly used to assess the outcomes of experimental
      infections in the frame of research experiments, rather than in routine
      monitoring of mosquito infection in the field. The present authors developed a
      novel mtDNA-based nested PCR protocol, modified from a loop-mediated isothermal
      amplification (LAMP) assay for Plasmodium recognition in human blood samples, and
      compared its performance with that of routinely used CSP-ELISAs in field
      collected Anopheles coluzzii (Diptera: Culicidae) samples. The nested PCR showed
      1.4-fold higher sensitivity than the CSP-ELISA. However, nested PCR results
      obtained in two laboratories and in different replicates within the same
      laboratory were not 100% consistent, probably because the copy number of
      amplifiable Plasmodium mtDNA was close in some specimens to the threshold of
      nested PCR sensitivity. This implies that Plasmodium-positive specimens should be
      confirmed by a second nested PCR to avoid false positives. Overall, the results
      emphasize the need to use molecular approaches to obtain accurate estimates of
      the actual level of Plasmodium circulation within malaria vector populations.

PMID- 29344969
TI  - Media experiences and associations with mental health among the bereaved of the
      MH17-disaster: A latent profile analysis.
AB  - Research has shown that the amount of media exposure is associated with post
      event mental health problems. Whether bereaved individuals have negative
      experiences with media reports and whether they are associated with post-event
      mental health is unclear. This study evaluated these experiences and associations
      following the MH17-disaster. How media reports were experienced (nine topics,
      modified MAS), depression symptoms (QIDS-SR), functional problems (WSAS) and
      event-related coping-self-efficacy (CSE) were assessed about one year post
      disaster (May-August 2015) among Dutch bereaved (N = 152). A substantial minority
      reported negative experiences such as reports made me angry (30%) and made me sad
      (48%). Latent profile analysis with symptoms, problems and coping self-efficacy
      as indicators, identified four classes of post-disaster mental health: a Well
      functioning(class 1) , 35.1%; a Mild-problems(class 2) , 30.4%; a Sub
      clinical(class 3) , 27.0%; and a Clinical(class 4) , 7.4%. Differences in
      symptoms, problems and coping self-efficacy levels between classes were large
      according to Cohen's ds. Multivariate logistic regression (MLR) showed that the
      Clinical(class 4) compared to the Well-functioning(class 1) , more often that
      felt that reports strongly "embarrassed me," "made me feel sad," "filled me with
      fear" and "served as a magnifying glass." Future research should assess
      opportunities and effects of limiting media consumption.

PMID- 29344970
TI  - Carbon allocation to major metabolites in illuminated leaves is not just
      proportional to photosynthesis when gaseous conditions (CO2 and O2 ) vary.
AB  - In gas-exchange experiments, manipulating CO2 and O2 is commonly used to change
      the balance between carboxylation and oxygenation. Downstream metabolism
      (utilization of photosynthetic and photorespiratory products) may also be
      affected by gaseous conditions but this is not well documented. Here, we took
      advantage of sunflower as a model species, which accumulates chlorogenate in
      addition to sugars and amino acids (glutamate, alanine, glycine and serine). We
      performed isotopic labelling with 13 CO2 under different CO2 /O2 conditions, and
      determined 13 C contents to compute 13 C-allocation patterns and build-up rates.
      The 13 C content in major metabolites was not found to be a constant proportion
      of net fixed carbon but, rather, changed dramatically with CO2 and O2 . Alanine
      typically accumulated at low O2 (hypoxic response) while photorespiratory
      intermediates accumulated under ambient conditions and at high photorespiration,
      glycerate accumulation exceeding serine and glycine build-up. Chlorogenate
      synthesis was relatively more important under normal conditions and at high CO2
      and its synthesis was driven by phosphoenolpyruvate de novo synthesis. These
      findings demonstrate that carbon allocation to metabolites other than
      photosynthetic end products is affected by gaseous conditions and therefore the
      photosynthetic yield of net nitrogen assimilation varies, being minimal at high
      CO2 and maximal at high O2 .

PMID- 29344971
TI  - Clear cell carcinomas of the ovary and kidney: clarity through genomics.
AB  - Clear cell ovarian carcinoma (CCOC) and clear cell renal cell carcinoma (ccRCC)
      both feature clear cytoplasm, owing to the accumulation of cytoplasmic glycogen.
      Genomic studies have demonstrated several mutational similarities between these
      two diseases, including frequent alterations in the chromatin remodelling SWI-SNF
      and cellular proliferation phosphoinositide 3-kinase-mammalian target of
      rapamycin pathways, as well as a shared hypoxia-like mRNA expression signature.
      Although many targeted treatment options have been approved for advanced-stage
      ccRCC, CCOC patients are still treated with conventional platinum and taxane
      chemotherapy, to which they are resistant. To determine the extent of similarity
      between these malignancies, we performed unsupervised clustering of mRNA
      expression data from these cancers. This review highlights the similarities and
      differences between these two clear cell carcinomas to facilitate knowledge
      translation within future research efforts. Copyright (c) 2018 Pathological
      Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

PMID- 29344972
TI  - A patient with chronic labial oedema and nodular palatal lesions.

PMID- 29344973
TI  - Use of Hysterosalpingo-Foam Sonography for Assessment of the Efficacy of Essure
      Hysteroscopic Sterilization.
AB  - OBJECTIVES: Hysterosalpingo-foam sonography (HyFoSy) has been suggested to be a
      possible less invasive alternative to hysterosalpingography (HSG), which is the
      reference standard for confirmation of tubal occlusion after Essure (Bayer AG,
      Leverkusen, Germany) hysteroscopic sterilization. The purpose of our study was to
      evaluate the accuracy of HyFoSy compared to HSG for confirmation of tubal
      occlusion after Essure hysteroscopic sterilization. METHODS: A prospective study
      included 90 patients who underwent Essure hysteroscopic sterilization. Twelve
      weeks after the sterilization, 2-dimensional transvaginal ultrasonography was
      performed to assess the microinsert position and was followed by HyFoSy and HSG
      for evaluation of tubal occlusion. Patients with patent fallopian tubes on HSG
      were scheduled for additional HSG procedures at 3-month intervals until tubal
      occlusion was documented. RESULTS: Of 90 enrolled patients, 86 patients with 170
      fallopian tubes underwent the complete imaging protocol. Tubal occlusion was
      evaluated by HyFoSy as an index test and HSG as a reference standard. The
      accuracy of HyFoSy was 97.1% (95% confidence interval [CI], 93%-99%). The
      sensitivity and specificity were 100% (95% CI, 97%-100%) and 54.6% (95% CI, 23%
      83%), whereas the positive and negative predictive values were 97.0% (95% CI, 93%
      99%) and 100% (95% CI, 42%-100%), respectively. No long-term complications were
      reported for HyFoSy or HSG. CONCLUSIONS: Given that the concordance rate for
      tubal occlusion between HyFoSy and HSG was not 100%, an occluded fallopian tube
      on HyFoSy should be confirmed by HSG, which remains the reference standard for
      confirmation of tubal occlusion after Essure hysteroscopic sterilization.

PMID- 29344974
TI  - Utilizing selected social determinants and behaviors to predict obesity in
      military personnel.
AB  - OBJECTIVE: Like the general population, the military is experiencing an increase
      in the number of obese personnel. This study aimed to identify predictors of
      obesity by assessing social determinants of health and behaviors in relation to
      Body Mass Index (BMI), and to use these variables to build a model to predict
      obesity in Active Duty Military Personnel (ADMP). Predicting obesity would allow
      early intervention of at risk personnel, potentially reducing the number of ADMP
      who are separated from the service for failing to meet weight standards. DESIGN:
      A secondary data analysis of the 2011 Survey of Health-Related Behaviors of
      Active Duty Military Personnel was performed. The survey included 39,197
      responders. MEASURES: Descriptive statistics, bivariate analyses, and logistic
      regression analysis were conducted to examine the relationship between social
      determinants of health, behaviors in relation to Healthy People 2020
      recommendations, and obesity. Moderator variables were used to determine what
      affects the direction and/or strength of the relationship between the independent
      variables (e.g., social determinants and behaviors) and the outcome variable of
      obesity. RESULTS: At the bivariate level, these variables mirror existing
      research. However, logistic regression identified few statistically significant
      obesogenic lifestyle behaviors in relation to Healthy People 2020 recommendations
      and a weak interactive effect between the variables. CONCLUSION: The low number
      of significant variables identified to predict obesity highlights the
      multifactorial nature of obesity making it difficult for weight-loss
      interventions to be effective if limited to one group or one specific behavior.

PMID- 29344976
TI  - Role of Elastography in Axillary Examination of Patients With Breast Cancer.
AB  - OBJECTIVES: This study aimed at exploring the role of ultrasound (US)
      elastography in the diagnosis of the axillary lymph node status in patients with
      breast cancer. METHODS: We analyzed 140 visible axillary lymph nodes on
      conventional US imaging. All of them underwent elastography. Five conventional US
      features were adopted to assess axillary lymph nodes: longitudinal diameter,
      longitudinal-to-transverse diameter ratio, cortical thickness, status of the
      hilum, and vascular pattern. As for elastography, the proportion of the hard area
      within each lymph node was estimated visually. The lymph node was defined as
      positive on elastography when the proportion was 50% or greater. Meanwhile,
      disjunctive and conjunctive combinations of US and elastography were adopted to
      evaluate the lymph nodes. The histopathologic diagnosis was regarded as the
      reference standard. RESULTS: The sensitivity, specificity, and accuracy were
      76.92%, 87.10%, and 81.43%, respectively, for conventional US and 84.62%, 83.87%,
      and 84.29% for the disjunctive combination. The conjunctive combination had
      specificity of 100% and a positive predictive value of 100%, whereas the
      sensitivity was low. CONCLUSIONS: Elastography can improve the sensitivity when
      disjunctively combined with conventional US for diagnosis of the axillary lymph
      node status. Despite the low sensitivity, the conjunctive combination of US and
      elastography can improve the positive predictive value on a large scale.
      Elastography is a useful adjuvant tool in addition to conventional US for the
      preoperative assessment of axillary lymph nodes in patients with breast cancer.

PMID- 29344977
TI  - There Is No Place Like Home: Imitation and the Politics of Recognition in
      Bolivian Obstetric Care.
AB  - This article examines how efforts to "culturally adapt" birthing spaces in a
      rural Bolivian hospital are generating debates among doctors about what
      constitutes proper obstetric care. Working at the intersection of national and
      transnational projects, NGOs in Bolivia have remade the birthing rooms of some
      public health institutions to look more like a home, with the goal of making
      indigenous women feel more comfortable and encouraging them to come to the clinic
      to give birth. Yet narratives of transformation also obscure ongoing conditions
      of racial and gendered inequality in health services. I demonstrate how doctors'
      use of culturally adapted technologies enacts shifting affective relations-warm,
      cold, gentle, harsh-that draws on preoccupations with indigenous culture as a
      threat to maternal and infant life. In tracing practices of care, I argue that
      culturally adapted birthing in many ways extends historically rooted practices of
      doing biomedical work on indigenous bodies.

PMID- 29344978
TI  - Letter to the editor.

PMID- 29344979
TI  - In vivo estimation of transverse relaxation time constant (T2 ) of 17 human brain
      metabolites at 3T.
AB  - PURPOSE: The transverse relaxation times T2 of 17 metabolites in vivo at 3T is
      reported and region specific differences are addressed. METHODS: An echo-time
      series protocol was applied to one, two, or three volumes of interest with
      different fraction of white and gray matter including a total number of 106
      healthy volunteers and acquiring a total number of 128 spectra. The data were
      fitted with the 2D fitting tool ProFit2, which included individual line shape
      modeling for all metabolites and allowed the T2 calculation of 28 moieties of 17
      metabolites. RESULTS: The T2 of 10 metabolites and their moieties have been
      reported for the first time. Region specific T2 differences in white and gray
      matter enriched tissue occur in 16 of 17 metabolites examined including single
      resonance lines and coupled spin systems. CONCLUSION: The relaxation time T2 is
      regions specific and has to be considered when applying tissue composition
      correction for internal water referencing. Magn Reson Med 80:452-461, 2018. (c)
      2018 International Society for Magnetic Resonance in Medicine.

PMID- 29344975
TI  - Extracellular matrix and traumatic brain injury.
AB  - The brain extracellular matrix (ECM) plays a crucial role in both the developing
      and adult brain by providing structural support and mediating cell-cell
      interactions. In this review, we focus on the major constituents of the ECM and
      how they function in both normal and injured brain, and summarize the changes in
      the composition of the ECM as well as how these changes either promote or inhibit
      recovery of function following traumatic brain injury (TBI). Modulation of ECM
      composition to facilitates neuronal survival, regeneration and axonal outgrowth
      is a potential therapeutic target for TBI treatment.

PMID- 29344980
TI  - Analytical validation of a new point-of-care assay for serum amyloid A in horses.
AB  - BACKGROUND: Serum amyloid A (SAA) is a major acute phase protein in horses. A new
      point-of-care (POC) test for SAA (Stablelab) is available, but studies evaluating
      its analytical accuracy are lacking. OBJECTIVES: To evaluate the analytical
      performance of the SAA POC test by 1) determining linearity and precision, 2)
      comparing results in whole blood with those in serum or plasma, and 3) comparing
      POC results with those obtained using a previously validated turbidimetric
      immunoassay (TIA). STUDY DESIGN: Assay validation. METHODS: Analytical validation
      of the POC test was done in accordance with American Society of Veterinary
      Clinical Pathology guidelines using residual equine serum/plasma and whole blood
      samples from the Clinical Pathology Laboratory at the University of California
      Davis. A TIA was used as the reference method. We also evaluated the effect of
      haematocrit (HCT). RESULTS: The POC test was linear for SAA concentrations of up
      to at least 1000 MUg/mL (r = 0.991). Intra-assay CVs were 13, 18 and 15% at high
      (782 MUg/mL), intermediate (116 MUg/mL) and low (64 MUg/mL) concentrations. Inter
      assay (inter-batch) CVs were 45, 14 and 15% at high (1372 MUg/mL), intermediate
      (140 MUg/mL) and low (56 MUg/mL) concentrations. SAA results in whole blood were
      significantly lower than those in serum/plasma (P = 0.0002), but were positively
      correlated (r = 0.908) and not affected by HCT (P = 0.261); proportional negative
      bias was observed in samples with SAA>500 MUg/mL. The difference between methods
      exceeded the 95% confidence interval of the combined imprecision of both methods
      (15%). MAIN LIMITATIONS: Analytical validation could not be performed in whole
      blood, the sample most likely to be used stall side. CONCLUSION: The POC test has
      acceptable accuracy and precision in equine serum/plasma with SAA concentrations
      of up to at least 1000 MUg/mL. Low inter-batch precision at high concentrations
      may affect serial measurements, and the use of the same test batch and sample
      type (serum/plasma or whole blood) is recommended. Comparison of results between
      the POC test and the TIA is not recommended.

PMID- 29344981
TI  - Severe and recurrent levamisole-induced cutaneous vasculopathy.

PMID- 29344982
TI  - Experience with pharmacologic leeching with bivalirudin for adjunct treatment of
      venous congestion of head and neck reconstructive flaps.
AB  - OBJECTIVES: The goal of this study was to review the feasibility of local
      bivalirudin injection for adjunct treatment of venous congestion of head and neck
      reconstructive flaps. METHODS: A retrospective chart review of patients who
      underwent bivalirudin treatment for venous congestion of head and neck
      reconstructive flaps in a single institution from September 1, 2012 to September
      1, 2015 was undertaken. Individuals were treated with variable number of
      intradermal injections directly into the flap followed by a small skin incision
      to allow extended passive bleeding. The main outcome measure was improvement of
      flap congestion. RESULTS: Ten patients with free flap reconstruction (4
      anterolateral thigh flaps, 2 pectoralis major flaps, 2 fibula osseocutaneous
      flaps, 1 supraclavicular flap, and 1 radial forearm free flap) of various head
      and neck defects underwent treatment with bivalirudin. Bivalirudin injections
      were utilized as adjunct therapy in 6 patients. Two individuals underwent
      alternate therapy for venous congestion immediately following injection and
      therefore the efficacy could not be assessed. Of the 8 remaining flaps, 4
      developed partial necrosis, and 1 developed complete necrosis requiring
      additional reconstruction. Two individuals required blood transfusions during
      bivalirudin treatment. CONCLUSIONS: Bivalirudin is a safe and feasible adjunct
      therapy for treatment of flap congestion. It may serve as a useful alternative to
      traditional leech therapy, as bivalirudin negates the need for antibiotic
      prophylaxis, eliminates the psychological aversion associated with leech therapy,
      and avoids the potential for leech migration. Further work to determine the
      efficacy of bivalirudin to standard leech therapy is warranted.

PMID- 29344984
TI  - The editors respond to Drs Mowat and Sheehan.

PMID- 29344983
TI  - Anti-inflammatory effect of 4-methylcyclopentadecanone in rats submitted to
      ischemic stroke.
AB  - This study aimed to investigate the anti-inflammatory effect of 4
      methylcyclopentadecanone (4-MCPC) in rats suffering from a cerebral
      ischemia/reperfusion (I/R) injury. In this study, the focal cerebral ischemia in
      rats was induced by middle cerebral artery occlusion (MCAO) for 2 h, and the rats
      were treated with 4-MCPC (8 mg/kg) just 0.5 h before reperfusion. The ischemic
      infarct volume was recorded 24 h after the MCAO. In addition, myeloperoxidase
      (MPO) activity and TNF-alpha and IL-1beta levels in the ischemic cerebral cortex
      were determined by ELISA, while nuclear translocation of NF-kappaB p65 subunit
      and expression of p-IkappaBalpha were investigated by Western blotting. Our
      results showed that 4-MCPC treatment decreased infarct volume significantly,
      compared with I/R group (16.8%+/-7.5% vs. 39.7%+/-10.9%); it reduced MPO activity
      (0.43 +/- 0.10 vs. 1.00 +/- 0.51 U/g) and expression levels of TNF-alpha (18.90
      +/- 3.65 vs. 35.87 +/- 4.87 ng/g) and IL-1beta (1.68 +/- 0.23 vs. 2.67 +/- 0.38
      ng/g) in ischemic brain tissues of rats. Further study revealed that 4-MCPC
      treatment markedly reduced nuclear translocation of NF-kappaB p65 subunit and
      expression of p-IkappaBalpha in ischemic cerebral cortex. Taken together, our
      results suggest that 4-MCPC protects against cerebral I/R injury and displays
      anti-inflammatory actions through inhibition of the NF-kappaB signal pathway.

PMID- 29344985
TI  - Probing the microscopic environment of 23 Na ions in brain tissue by MRI: On the
      accuracy of different sampling schemes for the determination of rapid,
      biexponential T2* decay at low signal-to-noise ratio.
AB  - PURPOSE: To investigate and to reduce influences on the determination of the
      short and long apparent transverse relaxation times ( T2,s*, T2,l*) of 23 Na in
      vivo with respect to signal sampling. METHODS: The accuracy of T2* determination
      was analyzed in simulations for five different sampling schemes. The influence of
      noise in the parameter fit was investigated for three different models. A
      dedicated sampling scheme was developed for brain parenchyma by numerically
      optimizing the parameter estimation. This scheme was compared in vivo to linear
      sampling at 7T. RESULTS: For the considered sampling schemes, T2,s* / T2,l*
      exhibit an average bias of 3% / 4% with a variation of 25% / 15% based on
      simulations with previously published T2* values. The accuracy could be improved
      with the optimized sampling scheme by strongly averaging the earliest sample. A
      fitting model with constant noise floor can increase accuracy while additional
      fitting of a noise term is only beneficial in case of sampling until late echo
      time > 80 ms. T2* values in white matter were determined to be T2,s* = 5.1 +/-
      0.8 / 4.2 +/- 0.4 ms and T2,l* = 35.7 +/- 2.4 / 34.4 +/- 1.5 ms using
      linear/optimized sampling. CONCLUSION: Voxel-wise T2* determination of 23 Na is
      feasible in vivo. However, sampling and fitting methods have to be chosen
      carefully to retrieve accurate results. Magn Reson Med 80:571-584, 2018. (c) 2018
      International Society for Magnetic Resonance in Medicine.

PMID- 29344986
TI  - Evaluation of bowel function in healthy children: untreated constipation is
      common.
AB  - AIM: We evaluated bowel function in healthy children with regard to gender and
      age. METHODS: The study was carried out in 2016 at a tertiary children's
      hospital. Healthy children aged 3.5 years to 15 years who were admitted to the
      hospital, siblings to patients or offspring of staff members were included.
      Validated self-report questionnaires and internally developed questions regarding
      obstructive outlet- and gas-related symptoms were used. RESULTS: A total of 310
      participants (50% girls) were included, which corresponded to a 94% answer
      frequency. Respondents were divided into a younger age group (3.5 years to seven
      years), consisting of 135 children, and an older age group (eight years to 15
      years), consisting of 175 children. Younger children reported more foul odours
      than older children (50% vs. 29%, p = 0.001) and more obstructive symptoms (21%
      vs. 10%, p = 0.01). There was no difference between the age groups regarding
      constipation (19% vs 16%, NS). Overall, 55% of those with constipation had no
      treatment for the condition, although they reported abdominal pain (51%) and
      problems with foul odours (57%). CONCLUSION: Healthy children frequently reported
      constipation, abdominal pain and gas-related problems, but treatment was rare.
      Overall, bowel function seemed to improve during childhood, although constipation
      remained largely untreated.

PMID- 29344987
TI  - Prior Uterine Evacuation and the Risk of Short Cervical Length: A Retrospective
      Cohort Study.
AB  - OBJECTIVES: To determine whether a prior uterine evacuation procedure is
      associated with an increased risk of short cervical length (<=20 mm) in women
      without prior spontaneous preterm birth. METHODS: This work was a retrospective
      cohort study from January 2012 to December 2014 of singletons without prior
      spontaneous preterm birth with cervical length screening between 18 weeks and 23
      weeks 6 days. Women with a prior miscarriage/abortion were excluded if management
      (medical, surgical, or expectant) was not specified. Prior uterine evacuation was
      defined as dilation and curettage or dilation and evacuation of a spontaneous or
      induced abortion. The primary outcome was the risk of short cervical length (<=20
      mm) among women with and without 1 of more prior uterine evacuations at any
      gestational age, assessed by the odds ratio and adjusted odds ratio for
      confounders. RESULTS: Of 2672 women included, 714 (27%) had at least 1 prior
      uterine evacuation. The overall incidence of short cervical length in the cohort
      was 1% (n = 27). Women with at least 1 prior uterine evacuation were more likely
      to be African American (64% versus 41%; P < .001), smoke (14% versus 8%; P <
      .001), have a higher body mass index (mean +/- SD, 28.1 +/- 7.1 versus 26.8 +/-
      7.1 kg/m2 ; P < .001), and have had prior full-term delivery (60% versus 41%; P <
      .001). Women with at least 1 prior uterine evacuation had a significantly higher
      incidence of short cervical length (2% versus 0.7%; P = .003; odds ratio, 2.99
      [95% confidence interval, 1.40-6.40]). After adjustment for confounders, prior
      uterine evacuation remained a source of increased risk of short cervical length
      (adjusted odds ratio, 2.63 [95% confidence interval, 1.19-5.80]). CONCLUSIONS:
      Although the overall incidence of short cervical length is low (1%-2%), women
      with at least 1 prior uterine evacuation have at least a 2-fold increased risk of
      a short second-trimester cervical length compared to women without a prior
      uterine evacuation.

PMID- 29344988
TI  - Recent advances in articular cartilage evaluation using computed tomography and
      magnetic resonance imaging.
AB  - Articular cartilage is a critical joint tissue and its evaluation remains a
      diagnostic challenge in horses. Coupled with a poor capacity for healing, early
      degenerative changes in articular cartilage are difficult to characterise using
      routine diagnostic imaging evaluations. Both computed tomography (CT) and
      magnetic resonance imaging (MRI) provide volumetric joint assessment and
      highlight morphological and quantitative properties of articular cartilage,
      improving assessment of this essential tissue. While the use of CT and MRI for
      joint evaluation is not new, there still remains a shortage of literature and
      scientific studies on the ability of these methods to evaluate articular
      cartilage in the horse. This review article summarises current CT and MRI
      techniques capable of characterising equine articular cartilage, highlights
      recent advances in these techniques and discusses the numerous methods studied in
      human subjects that have been minimally investigated in horses. Imaging
      techniques are presented in terms of their capabilities of offering morphological
      and quantitative evaluation along with a discussion of their benefits and
      limitations. Finally, it summarises the current state-of-the-art approaches and
      identifies unmet clinical imaging needs to propel the advancement of articular
      cartilage and joint imaging in the horse.

PMID- 29344989
TI  - Salmon calcitonin ameliorates migraine pain through modulation of CGRP release
      and dural mast cell degranulation in rats.
AB  - The exact mechanism of migraine pathophysiology still remains unclear due to the
      complex nature of migraine pain. Salmon calcitonin (SC) exhibits antinociceptive
      effects in the treatment of various pain conditions. In this study, we explored
      the mechanisms underlying the analgesic effect of salmon calcitonin on migrane
      pain using glyceryltrinitrate (GTN)-induced model of migraine and ex vivo
      meningeal preparations in rats. Rats were intraperitoneally administered saline,
      GTN (10 mg/kg), vehicle, saline + GTN, SC (50 MUg/kg) + GTN, and SC alone. Also,
      ex vivo meningeal preparations were applied topically 100 MUmol/L GTN, 50 MUmol/L
      SC, and SC + GTN. Calcitonin gene-related peptide (CGRP) contents of plasma,
      trigeminal neurons and superfusates were measured using enzyme-immunoassays.
      Dural mast cells were stained with toluidine blue. c-fos neuronal activity in
      trigeminal nucleus caudalis (TNC) sections were determined by immunohistochemical
      staining. The results showed that GTN triggered the increase in CGRP levels in
      plasma, trigeminal ganglion neurons and ex vivo meningeal preparations. Likewise,
      GTN-induced c-fos expression in TNC. In in vivo experiments, GTN caused dural
      mast cell degranulation, but similar effects were not seen in ex vivo
      experiments. Salmon calcitonin administration ameliorated GTN-induced migraine
      pain by reversing the increases induced by GTN. Our findings suggested that
      salmon calcitonin could alleviate the migraine-like pain by modulating CGRP
      release at different levels including the generation and conduction sites of
      migraine pain and mast cell behaviour in the dura mater. Therefore salmon
      calcitonin may be a new therapeutic choice in migraine pain relief.

PMID- 29344990
TI  - Self-gated golden-angle spiral 4D flow MRI.
AB  - PURPOSE: The acquisition of 4D flow magnetic resonance imaging (MRI) in
      cardiovascular applications has recently made large progress toward clinical
      feasibility. The need for simultaneous compensation of cardiac and breathing
      motion still poses a challenge for widespread clinical use. Especially, breathing
      motion, addressed by gating approaches, can lead to unpredictable and long scan
      times. The current work proposes a time-efficient self-gated 4D flow sequence
      that exploits up to 100% of the acquired data and operates at a predictable scan
      time. METHODS: A self-gated golden-angle spiral 4D flow sequence was implemented
      and tested in 10 volunteers. Data were retrospectively binned into respiratory
      and cardiac states and reconstructed using a conjugate-gradient sensitivity
      encoding reconstruction. Net flow curves, stroke volumes, and peak flow in the
      aorta were evaluated and compared to a conventional Cartesian 4D flow sequence.
      Additionally, flow quantities reconstructed from 50% to 100% of the self-gated 4D
      flow data were compared. RESULTS: Self-gating signals for respiratory and cardiac
      motion were extracted for all volunteers. Flow quantities were in agreement with
      the standard Cartesian scan. Mean differences in stroke volumes and peak flow of
      7.6 +/- 11.5 and 4.0 +/- 79.9 mL/s were obtained, respectively. By
      retrospectively increasing breathing navigator efficiency while decreasing
      acquisition times (15:06-07:33 minutes), 50% of the acquired data were sufficient
      to measure stroke volumes with errors under 9.6 mL. CONCLUSION: The feasibility
      to acquire respiratory and cardiac self-gated 4D flow data at a predictable scan
      time was demonstrated. Magn Reson Med 80:904-913, 2018. (c) 2018 International
      Society for Magnetic Resonance in Medicine.

PMID- 29344991
TI  - Relationship between enamel bond fatigue durability and surface free-energy
      characteristics with universal adhesives.
AB  - The relationship between enamel bond fatigue durability and surface free-energy
      characteristics with universal adhesives was investigated. The initial shear bond
      strengths and shear fatigue strengths of five universal adhesives to enamel were
      determined with and without phosphoric acid pre-etching. The surface free-energy
      characteristics of adhesive-treated enamel with and without pre-etching were also
      determined. The initial shear bond strength and shear fatigue strength of
      universal adhesive to pre-etched enamel were higher than those to ground enamel.
      The initial shear bond strength and shear fatigue strength of universal adhesive
      to pre-etched enamel were material dependent, unlike those to ground enamel. The
      surface free-energy of the solid (gammaS ) and the hydrogen-bonding force
      (gammaSh) of universal adhesive-treated enamel were different depending on the
      adhesive, regardless of the presence or absence of pre-etching. The bond fatigue
      durability of universal adhesives was higher to pre-etched enamel than to ground
      enamel. In addition, the bond fatigue durability to pre-etched enamel was
      material dependent, unlike that to ground enamel. The surface free-energy
      characteristics of universal adhesive-treated enamel were influenced by the
      adhesive type, regardless of the presence or absence of pre-etching. The surface
      free-energy characteristics of universal adhesive-treated enamel were related to
      the results of the bond fatigue durability.

PMID- 29344992
TI  - An immunohistochemical score to predict the outcome for oral squamous cell
      carcinoma.
AB  - BACKGROUND: Oral cancer is a major public health problem worldwide, with a poor
      survival. Our aim was to evaluate several protein markers in oral squamous cell
      carcinomas (OSCC) and analyse their prognostic value on patient's survival.
      METHODS: We analysed the expression of EGFR, p53, p27, p16, cyclin D1, cyclin A2,
      COX-2, Ki-67, Bcl-2, VEGFR-1 and VEGFR-2, by immunohistochemistry on 67 primary
      OSCC. Cancer-specific survival (CSS) analysis was evaluated by the Cox regression
      model. RESULTS: Markers showed variable expression between 27.9% and 95.2%. In
      univariate analysis for CSS, we found that four of the tested markers, namely
      high expression of p53 (P = .001), EGFR (P = .003), cyclin A2 (P = .005) and low
      expression of p16 (P = .019), along with clinical stage (P < .001), tumour size
      (P < .001), presence of nodal metastasis (P < .001) and perineural permeation (P
      = .039) were related to decreased survival. On the basis of these results, we
      constructed an immunohistochemical score hinging on the possibility that any
      tumour could express none of these four markers (score 0), one or two markers
      (score 1) and three or more markers (score 2). In multivariable analysis, this
      immunohistochemical score revealed an independent prognostic value on cancer
      specific survival (P = .001; HR: 3.7: 95%CI 1.7-7.9). Moreover, we confirmed that
      in early-stage tumours (stage I or II) this score maintained its independent
      prognostic value (P = .025; HR: 7.9, 95%CI 1.3-49.1) on CSS. CONCLUSION: The
      expression of the markers p53, p16, EGFR and cyclin A in OSCC, combined to give
      an immunohistochemical score, may identify high-risk subgroups for decreased
      survival and to further guide therapeutic decisions.

PMID- 29344993
TI  - Editorial Comment to Cell death under epithelial-mesenchymal transition control
      in prostate cancer therapeutic response.

PMID- 29344994
TI  - Embryology of the craniocervical junction and posterior cranial fossa, part II:
      Embryogenesis of the hindbrain.
AB  - Although pathology of the hindbrain and its derivatives can have life altering
      effects on a patient, a comprehensive review on its embryology is difficult to
      find in the peer-reviewed medical literature. Therefore, this review article,
      using standard search engines, seemed timely. The embryology of the hindbrain is
      complex and relies on a unique timing of various neurovascular and bony elements.
      Derailment of these developmental processes can lead to a wide range of
      malformations such as the Chiari malformations. Therefore, a good working
      knowledge of this embryology as outlined in this review of the hindbrain is
      important for those treating patients with involvement of this region of the
      central nervous system. Clin. Anat. 31:488-500, 2018. (c) 2018 Wiley Periodicals,
      Inc.

PMID- 29344995
TI  - Activation of human CD141+ and CD1c+ dendritic cells in vivo with combined TLR3
      and TLR7/8 ligation.
AB  - Mice reconstituted with human hematopoietic stem cells are valuable models to
      study aspects of the human immune system in vivo. We describe a humanized mouse
      model (hu mice) in which fully functional human CD141+ and CD1c+ myeloid and
      CD123+ plasmacytoid dendritic cells (DC) develop from human cord blood CD34+
      cells in immunodeficient mice. CD141+ DC are the human equivalents of murine CD8+
      /CD103+ DC which are essential for the induction of tumor-inhibitory cytotoxic T
      lymphocyte responses, making them attractive targets to exploit for the
      development of new cancer immunotherapies. We used CD34+ -engrafted NSG-A2 mice
      to investigate activation of DC subsets by synthetic dsRNA or ssRNA analogs
      polyinosinic-polycytidylic acid/poly I:C and Resiquimod/R848, agonists for TLR3
      and TLR8, respectively, both of which are expressed by CD141+ DC. Injection of hu
      mice with these agonists resulted in upregulation of costimulatory molecules
      CD80, CD83 and CD86 by CD141+ and CD1c+ DC alike, and their combination further
      enhanced expression of these molecules by both subsets. When combined, poly I:C
      and R848 enhanced serum levels of key cytokines associated with cross
      presentation and the induction of cytotoxic T lymphocyte responses including IFN
      alpha, IFN-beta, IL-12 and CXCL10. These data advocate a combination of poly I:C
      and R848 TLR agonists as means of activating human DC for immunotherapy.

PMID- 29344996
TI  - Bibliometric analysis of a century of research on oral erythroplakia and
      leukoplakia.
AB  - BACKGROUND: Oral squamous cell carcinoma is a major cause of cancer-associated
      morbidity and mortality and may develop from oral erythroplakia and leukoplakia
      (OEL), the most common oral potentially malignant lesions. Our objective was to
      provide a descriptive overview of the global research activity on OEL over the
      past decades. METHODS: We performed a systematic bibliometric analysis of
      articles and reviews on OEL up to December 31st 2016 using the SCOPUS database.
      Contribution of each country was analyzed by density-equalizing mapping (DEMP).
      The overall scientific productivity was analyzed for each journal and country.
      RESULTS: A total of 5098 published items (articles or reviews) were identified.
      They are expected to double by 2040, with an expected number of 400 items per
      year. Only 4% of all research on oral oncology is focused on OEL. Together with
      the increasing number of publications since 1980s, an increasing number of
      international collaborative studies were observed. Journal of Oral Pathology and
      Medicine and Oral Oncology are the leading journals in terms of number of
      published items. The US, India, and the UK were the most prolific countries in
      terms of publications overtime. CONCLUSIONS: We identified the leading journals
      as well as the leading authors and countries contributing to the research on OEL.
      International collaborative studies in the field are to be encouraged to refine
      strategies of oral cancer prevention.

PMID- 29344997
TI  - Integration of Open Metal Sites and Lewis Basic Sites for Construction of a Cu
      MOF with a Rare Chiral Oh -type cage for high performance in methane
      purification.
AB  - A Cu metal-organic framework (MOF), [Cu4 (PMTD)2 (H2 O)3 ]?20 H2 O, 1, (where
      PMTD is 1,4-phenylenebis(5-methyl-4H-1,2,4-triazole-3,4-diyl)bis(5-carboxylato
      3,1-phenylene)bis(hydroperoxymethanide)), with a rare chiral Oh -type cage, and
      dual functionalities of open metal sites and Lewis basic sites, based on a
      designed U-shaped ligand, was synthesized by hydrothermal methods. It exhibits
      high CO2 , C2 , and C3 hydrocarbon storage capacity under atmospheric pressure,
      as well as high H2 (1.96 wt.%) adsorption capacity at 77 K. Methane purification
      capacity was tested and verified step by step. Isosteric heats (Qst ) studies
      reveal that CH4 has the weakest van der Waals host-guest interactions among the
      seven gases at 298 K. Ideal adsorbed solution theory (IAST) calculation reveals
      that compound 1 is more selective toward CO2 , C2 H6 , and C3 H8 over CH4 in
      further calculating its separation capacity, as exemplified for CO2 /CH4 (50:50,
      5:95), C2 H6 /CH4 (50:50, 5:95), or C3 H8 /CH4 (50:50, 5:95) binary gas mixtures.
      Breakthrough experiments show that 1 has a significantly higher adsorption
      capacity for CO2 , C2 H6 , and C3 H8 than CH4 . The selective adsorption
      properties of 1 make it a promising candidate for methane purification.

PMID- 29344998
TI  - Role of AP-endonuclease (Ape1) active site residues in stabilization of the
      reactant enzyme-DNA complex.
AB  - Apurinic/apyrimidinic endonuclease 1 (Ape1) is an important metal-dependent
      enzyme in the base excision repair mechanism, responsible for the backbone
      cleavage of abasic DNA through a phosphate hydrolysis reaction. Molecular
      dynamics simulations of Ape1 complexed to its substrate DNA performed for models
      containing 1 or 2 Mg2+ -ions as cofactor located at different positions show a
      complex with 1 metal ion bound on the leaving group site of the scissile
      phosphate to be the most likely reaction-competent conformation. Active-site
      residue His309 is found to be protonated based on pKa calculations and the higher
      conformational stability of the Ape1-DNA substrate complex compared to scenarios
      with neutral His309. Simulations of the D210N mutant further support the
      prevalence of protonated His309 and strongly suggest Asp210 as the general base
      for proton acceptance by a nucleophilic water molecule.

PMID- 29344999
TI  - The newer classifications of the chiari malformations with clarifications: An
      anatomical review.
AB  - In 1891, Hans Chiari described a group of congenital hindbrain anomalies, which
      were eventually named after him. He classified these malformations into three
      types (Chiari malformations I, II, and III), and four years later added the
      Chiari IV malformation. However, numerous reports across the literature do not
      seem to fit Chiari's original descriptions of these malformations, so researchers
      have been encouraged to propose new classifications to encompass these variants
      (e.g., Chiari 0, Chiari1.5, and Chiari 3.5 malformations). Moreover, there is a
      continued misunderstanding and misuse of the term "Chiari IV malformation."
      Therefore, the current review intended to describe anatomical,
      pathophysiological, and clinical aspects of the newer classifications with
      clarifications of the Chiari malformations. We reviewed available literature
      about Chiari malformations and their variants using "PubMed" and "Google
      Scholar." We also looked into the term Chiari IV, clarifying its original
      description and citing examples where the term has been used erroneously.
      References in the reviewed articles were searched manually. Variants of the
      originally described Chiari malformations are termed Chiari 0, Chiari 1.5, and
      Chiari 3.5. Each has distinct anatomical characteristics and some of these are
      extremely rare and incompatible with life (e.g. Chiari 3.5). Chiari IV
      malformation has been further clarified. Some physicians might be unfamiliar with
      the newer classifications of Chiari malformations because these conditions are
      rare or even unique. Furthermore, care is needed in using the term "Chiari IV
      malformation", which must be consistent with Chiari's original description, i.e.
      an occipital encephalocele containing supratentorial contents. Clin. Anat. 31:314
      322, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 29345000
TI  - Cell death under epithelial-mesenchymal transition control in prostate cancer
      therapeutic response.
AB  - Prostate cancer is a widespread problem among men, with >160 000 new cases in
      2017 alone. Androgen deprivation therapy is commonly used in prostate cancer
      treatment to block androgens required for cancer growth, but disease relapse
      after androgen deprivation therapy is both common and severe. Changes in androgen
      receptor signaling from androgen deprivation therapy have been linked to
      therapeutic resistance and tumor progression. Resistant cells can become
      reprogrammed to undergo epithelial-mesenchymal transition, a phenotypic switch
      from benign, epithelial cells to a mobile cell with mesenchymal traits. In these
      cells, attachment to their epithelial cell layer is no longer required for
      survival. Anoikis is a form of cell death that occurs when detachment from other
      cells and the basement membrane occurs. Epithelial cells have been shown to
      undergo epithelial-mesenchymal transition, avoid anoikis induction and progress
      to a metastatic phenotype. In prostate cancer progression to advanced disease,
      epithelial-mesenchymal transition induction (characterized by loss of epithelial
      cellular attachment protein E-cadherin) correlates with a higher Gleason score,
      tumor progression, increased metastasis and higher biochemical recurrence. The
      concept of interfacing epithelial-mesenchymal transition with anoikis in the
      tumor microenvironment landscape will be discussed here, with focus on the
      significance of the functional exchange between the two processes in therapeutic
      targeting of advanced disease. The current evidence on the impact of loss of cell
      cell contact, acquisition of chemoresistance, immune escape and metastatic spread
      in advanced tumors in response to transforming growth factor-beta on prostate
      cancer metastasis will be also discussed. The signaling cross-talk between
      transforming growth factor-beta and androgen receptor signaling will be
      interrogated as a new therapeutic platform for the development of combination
      strategies to impair prostate cancer metastasis.

PMID- 29345001
TI  - Wheat oral immunotherapy was moderately successful but was associated with very
      frequent adverse events in children aged 6-18 years.
AB  - AIM: This study investigated oral immunotherapy (OIT) for children aged 6-18
      years with wheat allergies. METHODS: Well-cooked wheat spaghetti was given to 100
      children with wheat allergies every day for 17 weeks, increasing from 0.3 to 2000
      mg of wheat protein, followed by three- and nine-month maintenance phases. Blood
      samples were taken before therapy and at follow-up visits. The study was carried
      out in 2009-2015 in four Finnish paediatric allergology units. RESULTS: The
      children (67% male) had a mean age of 11.6 years (range 6.1-18.6), and 57 were
      using wheat daily 16 months after the initiation of therapy. Allergic symptoms
      occurred in 94/100 children: mild in 34, moderate in 36 and severe in 24.
      Specific immunoglobulin E (IgE) for omega-5-gliadin was significantly higher in
      patients who did not reach the target dose and were related to the intensity of
      reactions. CONCLUSION: The majority (57%) of children with wheat allergies could
      use wheat in their daily diet 16 months after the initiation of OIT, but 94/100
      had adverse reactions and 60 were moderate or severe. Specific IgE to omega-5
      gliadin may provide a biomarker for how much wheat can be tolerated and the
      intensity of the reactions to immunotherapy.

PMID- 29345002
TI  - Remote C-H Activation of Various N-Heterocycles Using a Single Template.
AB  - A single and simple ortho-sulfonyl benzonitrile template was developed to achieve
      remote C-H olefination of six different classes of N-heterocycles. We demonstrate
      that, by varying precatalysts and conditions, the same template can be applied to
      the remote C-H activation of six structurally distinct heterocyclic scaffolds,
      and the site-selectivity can be predicted based on distance and geometry.
      Furthermore, this new development shows that template-directed remote C-H
      activation is possible through macrocyclopalladation processes with smaller ring
      sizes.

PMID- 29345003
TI  - Investigation of attributes which guide choice in cataract surgery services in
      urban Sydney, Australia.
AB  - BACKGROUND: It is critical to consult patients to develop patient-centred
      cataract surgery care. We aimed to identify attributes patients consider when
      making decisions about cataract surgery in an Australian context, where both
      publicly and privately funded surgery are available. This is the first step in
      investigating how decisions are made about cataract surgery services. METHODS:
      This observational qualitative study was undertaken in two public hospitals and
      one private practice in Sydney, Australia. The study involved 19 women and men
      with age-related cataracts and no previous cataract surgery, aged > 18 years,
      able to speak conversational English or Mandarin. A multi-stage attribute
      development process was followed, including: literature review, semi-structured
      interviews with surgery candidates in three eye clinics, and review by an expert
      panel. The main outcome measures were primary attributes for making choices about
      cataract surgery. RESULTS: Wait time, cost, institutional reputation, surgeon
      experience and travel time were identified as principal attributes; lower value
      was placed on consultation length and accessibility. Non-English speaking
      participants indicated greater interest in pre-operative information than English
      speakers, but expressed trust in the Australian healthcare system. CONCLUSIONS:
      Findings suggest individuals prioritise attributes which consume time or incur
      costs when accessing care (wait time, cost and travel time). They also consider
      factors associated with the outcome of their cataract surgery (surgeon experience
      and institutional reputation). Similar to other decision-making processes,
      patients are likely to trade between these different attributes depending on
      their personal preferences and circumstances.

PMID- 29345004
TI  - Epidermal permeability barrier function and sphingolipid content in the skin of
      sphingomyelin synthase 2 deficient mice.
AB  - Sphingomyelin synthase (SMS) is an enzyme that generates sphingomyelin (SM) from
      ceramide (CER) and phosphatidylcholine. SM in the epidermis is a precursor of
      CER, an important lipid for epidermal permeability barrier function. However, the
      physiological role of SMS in skin is unclear. To uncover the function of SMS in
      skin, we investigated sphingolipid metabolism enzyme activity in skin, SM content
      in the epidermis, CER content in the stratum corneum (SC) and transepidermal
      water loss (TEWL) as an indicator of barrier function in SMS2-knockout (KO) mice.
      The activities of sphingolipid metabolism enzymes in skin homogenates were
      measured using a fluorescently labelled substrate. Enzymatic reaction products
      were detected by high-performance liquid chromatography (HPLC). Lipids in the
      epidermis or SC were extracted and quantified by high-performance thin layer
      chromatography (HPTLC). TEWL was measured using a Tewameter TM300. In SMS2-KO
      mice, SMS activity in skin homogenates, epidermal SM content and SC CER content
      were significantly decreased relative to wild-type (WT) mice. The TEWL of SMS2-KO
      mice was significantly increased compared to WT mice. Our data indicate that SMS2
      generates SM in the epidermis and contributes to epidermal permeability barrier
      function and will support understanding of SM-related metabolic disorders.

PMID- 29345005
TI  - "There's no acknowledgement of what this does to people": A qualitative
      exploration of mental health among parents of children with critical congenital
      heart defects.
AB  - AIMS AND OBJECTIVES: The purpose of this study was to explore the psychological
      impact of parenting a child with a critical congenital heart defect and the
      feasibility and acceptability of integrating psychological services into
      paediatric cardiology care. BACKGROUND: Children with critical congenital heart
      defect are at an increased risk for long-term behavioural, social and emotional
      difficulties. Data suggest that this risk is partially attributable to parental
      mental health, which is a stronger predictor of long-term behavioural problems in
      congenital heart defect children than disease-specific and surgical factors.
      Parental stress and mental health are thus important intervention targets,
      especially among high-risk families. DESIGN: This article presents data from a
      qualitative study with 25 congenital heart defect parents (n = 15) and providers
      (n = 10). METHODS: Using thematic analysis, semi-structured in-depth interviews
      were transcribed and coded by the first and second author to identify major
      themes and subthemes. RESULTS: Results of the interviews were organised into four
      major themes: (i) the psychological impact of parenting a child with critical
      congenital heart defect, (ii) factors that influence the psychological impact of
      parenting a child with critical congenital heart defect, (iii) how and when to
      psychologically support congenital heart defect parents and (iv) feasibility and
      acceptability of integrating psychological support into congenital heart defect
      care. Providers and parents endorsed the integration of mental health treatment
      into routine congenital heart defect care and identified several practical issues
      related to feasibility (e.g., funding and space) that should be considered prior
      to implementation. CONCLUSIONS: Parents of children with critical congenital
      heart defect need access to mental health services, and integrating these
      services into routine paediatric cardiology care is a novel and practical way for
      parents to receive the treatment they need. RELEVANCE TO CLINICAL PRACTICE:
      Suggestions for how the field of paediatric cardiology could begin to integrate
      mental health services into congenital heart defect treatment are provided.

PMID- 29345006
TI  - Embryology of the craniocervical junction and posterior cranial fossa, part I:
      Development of the upper vertebrae and skull.
AB  - Although the embryology of the posterior cranial fossa can have life altering
      effects on a patient, a comprehensive review on this topic is difficult to find
      in the peer-reviewed medical literature. Therefore, this review article, using
      standard search engines, seemed timely. The embryology of the posterior cranial
      fossa is complex and relies on a unique timing of various neurovascular and bony
      elements. Derailment of these developmental processes can lead to a wide range of
      malformations such as the Chiari malformations. Therefore, a good working
      knowledge of this embryology as outlined in this review of its bony architecture
      is important for those treating patients with involvement of this region of the
      cranium. Clin. Anat. 31:466-487, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 29345007
TI  - Aetiology of neonatal conjunctivitis evaluated in a population-based setting.
AB  - AIM: Our aim was to study prospectively the aetiology of neonatal conjunctivitis
      in a population-based setting. METHODS: Altogether 173 neonates with clinical
      conjunctivitis aged on average 20 (SD 10) days were recruited from child welfare
      clinics in Oulu, Finland, in 2010-2015. Conjunctival specimens were collected
      from 167 neonates for multiplex polymerase chain reaction to detect 16
      respiratory viruses, from 163 for polymerase chain reaction to detect Chlamydia
      trachomatis and Neisseria gonorrhoeae and from 160 for bacterial culture studies.
      The cases were followed up until the age of 18 months. RESULTS: Viral
      conjunctivitis was diagnosed in 8/167 (4.8%; 95% CI 2.1-9.2%), chlamydial or
      gonococcal conjunctivitis in 0/163 cases (0%; 95% CI 0-2.2%) and other bacterial
      conjunctivitis in 58/160 (36%; 95% CI 29-44%). Rhinovirus was found at the ocular
      site in 4/167 (2.4%) neonates, adenovirus in 3/167 (1.8%) and bocavirus in 1/167
      (0.6%). The most commonly isolated bacteria included Staphylococcus aureus (16%),
      Moraxella catarrhalis (9.4%) and Streptococcus pneumoniae (3.1%). None of these
      pathogens was associated with the 4/173 (2.3%) cases later operated on for
      persistent nasolacrimal duct obstruction. CONCLUSION: Chlamydia trachomatis was a
      rare pathogen in neonatal conjunctivitis in a population-based setting, but
      respiratory viruses were detected more frequently than indicated earlier.

PMID- 29345008
TI  - Current knowledge of risk factors for testicular germ cell tumors.
AB  - The development of the human gonads is tightly regulated by the correct
      sequential expression of many genes and hormonal activity. Disturbance of this
      regulation does not only prevent proper development of the gonads, but it also
      contributes to the development of testicular germ cell tumors. Recent genetic
      studies, especially genome-wide association studies, have made great progress in
      understanding genetic susceptibility. Although there is strong evidence of
      inherited risks, many environmental factors also contribute to the development of
      testicular germ cell tumors. Histopathological studies have shown that most
      testicular germ cell tumors arise from germ cell neoplasia in situ, which is
      thought to be arrested and transformed primordial germ cells. Seminoma has
      features identical to germ cell neoplasia in situ or primordial germ cells,
      whereas non-seminoma shows varied differentiation. Seminomas and embryonic cell
      carcinomas have the feature of pluripotency, which is thought to be the cause of
      histological heterogeneity and mixed pathology in testicular germ cell tumors.
      Testicular germ cell tumors show high sensitivity to chemotherapies, but 20-30%
      of patients show resistance to standard chemotherapy. In the present review, the
      current knowledge of the epidemiological and genomic factors for the development
      of testicular germ cell tumors is reviewed, and the mechanisms of resistance to
      chemotherapies are briefly mentioned.

PMID- 29345009
TI  - Choosing non-redundant representative subsets of protein sequence data sets using
      submodular optimization.
AB  - Selecting a non-redundant representative subset of sequences is a common step in
      many bioinformatics workflows, such as the creation of non-redundant training
      sets for sequence and structural models or selection of "operational taxonomic
      units" from metagenomics data. Previous methods for this task, such as CD-HIT,
      PISCES, and UCLUST, apply a heuristic threshold-based algorithm that has no
      theoretical guarantees. We propose a new approach based on submodular
      optimization. Submodular optimization, a discrete analogue to continuous convex
      optimization, has been used with great success for other representative set
      selection problems. We demonstrate that the submodular optimization approach
      results in representative protein sequence subsets with greater structural
      diversity than sets chosen by existing methods, using as a gold standard the
      SCOPe library of protein domain structures. In this setting, submodular
      optimization consistently yields protein sequence subsets that include more SCOPe
      domain families than sets of the same size selected by competing approaches. We
      also show how the optimization framework allows us to design a mixture objective
      function that performs well for both large and small representative sets. The
      framework we describe is the best possible in polynomial time (under some
      assumptions), and it is flexible and intuitive because it applies a suite of
      generic methods to optimize one of a variety of objective functions.

PMID- 29345010
TI  - Genetic variation in the shape of cold-survival curves in a single fly population
      suggests potential for selection from climate variability.
AB  - Temperature variation is one of the primary challenges facing ectotherms, and the
      ability to tolerate a range of thermal environments is critical for setting
      current and future species distributions. Low temperature is particularly
      challenging for ectotherms because winter conditions have strong latitudinal and
      temporal variation. Lower lethal temperature (LLT) is a common metric of cold
      tolerance used in studies of local adaptation and plasticity. Comparisons of LLT
      across groups typically assume parallel S-shaped survival curves, but genetic
      variation in the shape of survival vs. temperature curves has not been assessed.
      Here, we measured the ability of 36 lines of the Drosophila Genetic Reference
      Panel (DGRP) to survive a 1-h cold shock at seven ecologically relevant low
      temperatures (-1 to -7  degrees C) to create a high-resolution response curve for
      each genotype. We observed surprising variation both in the magnitude of survival
      and in the shapes of the response curves, with the curves clustering into four
      distinct shapes. To encompass variation in the shapes of these survival curves,
      we developed a new cold tolerance metric, cumulative cold tolerance (CCT). By
      comparing our survival data with climatological data, we propose that variation
      in the shapes of cold-survival curves arose from weak selection pressure to
      survive intermediate subzero temperatures in this mid-latitude population of
      flies. Using publicly available genome sequence and transcript expression data
      for these lines, we identified several candidate genes associated with CCT, and
      using transgenic RNAi, we confirmed a functional role for many of these genes.

PMID- 29345011
TI  - Effectiveness of a patient education plan on knowledge of post-op venous
      thromboembolism survival skills.
AB  - AIMS AND OBJECTIVES: To investigate the effectiveness of a multimethod venous
      thromboembolism prevention patient education plan on participants' knowledge
      retention. BACKGROUND: A potential complication of surgery requiring general
      anaesthesia, worldwide, is the development of life-threatening venous
      thromboembolism. Patients need education on preventing, recognising and
      immediately responding to a suspected thromboembolism. Written instructional
      materials given to patients at discharge may be inadequate. DESIGN: A randomised
      controlled trial. METHODS: Setting was multiple general surgery units at a large
      Midwestern United States academic medical centre. Sample included patients
      recovering from surgery with general anaesthesia: (N = 66), 68% female, 34 =
      experimental, 32 = usual care. Prior to discharge, participants in the
      experimental group were given a multimethod venous thromboembolism prevention
      education plan including a video, pamphlet and verbal instruction; control group
      received usual instructional pamphlet. Both groups received a knowledge test
      immediately before instruction. Two weeks following discharge, a phone call was
      made to participants to complete the postinstruction test. The relevant EQUATOR
      guideline, CONSORT checklist, was used for reporting this study. CONCLUSIONS:
      There were no statistically significant differences in age, gender, race, length
      of stay, surgery and history of venous thromboembolism among participants and
      group or test score results. No statistically significant difference in
      postinstruction score was found between groups. However, there was a trend in
      greater perception of importance in all groups and higher knowledge scores in the
      experimental group, with the percentage of participants in the experimental group
      answering all questions correctly rising from 38.2% correct to 73.5% correct.
      RELEVANCE TO CLINICAL PRACTICE: Teaching patients the importance of knowing
      venous thromboembolism signs and preventive/survival skills is potentially life
      saving and nurses must know the importance of using the most effective methods
      for the learning needs of their patients. Further research including different
      education methods and testing is suggested.

PMID- 29345012
TI  - In Reply to Letter to the Editor from Bhartiya: Transplantation of Whole Bone
      Marrow Indicates That Bone Marrow Very Small Embryonic-Like Cells Do Not
      Contribute to Endometrial Lineages.

PMID- 29345013
TI  - Reliability and criterion-related validity testing (construct) of the
      Endotracheal Suction Assessment Tool (ESAT(c)).
AB  - AIMS AND OBJECTIVES: To establish criterion-related construct validity and test
      retest reliability for the Endotracheal Suction Assessment Tool(c) (ESAT(c)).
      BACKGROUND: Endotracheal tube suction performed in children can significantly
      affect clinical stability. Previously identified clinical indicators for
      endotracheal tube suction were used as criteria when designing the ESAT(c).
      Content validity was reported previously. The final stages of psychometric
      testing are presented. DESIGN: Observational testing was used to measure
      construct validity and determine whether the ESAT(c) could guide "inexperienced"
      paediatric intensive care nurses' decision-making regarding endotracheal tube
      suction. Test-retest reliability of the ESAT(c) was performed at two time points.
      METHODS: The researchers and paediatric intensive care nurse "experts" developed
      10 hypothetical clinical scenarios with predetermined endotracheal tube suction
      outcomes. "Experienced" (n = 12) and "inexperienced" (n = 14) paediatric
      intensive care nurses were presented with the scenarios and the ESAT(c) guiding
      decision-making about whether to perform endotracheal tube suction for each
      scenario. Outcomes were compared with those predetermined by the "experts" (n =
      9). Test-retest reliability of the ESAT(c) was measured at two consecutive time
      points (4 weeks apart) with "experienced" and "inexperienced" paediatric
      intensive care nurses using the same scenarios and tool to guide decision-making.
      RESULTS: No differences were observed between endotracheal tube suction decisions
      made by "experts" (n = 9), "inexperienced" (n = 14) and "experienced" (n = 12)
      nurses confirming the tool's construct validity. No differences were observed
      between groups for endotracheal tube suction decisions at T1 and T2. CONCLUSION:
      Criterion-related construct validity and test-retest reliability of the ESAT(c)
      were demonstrated. Further testing is recommended to confirm reliability in the
      clinical setting with the "inexperienced" nurse to guide decision-making related
      to endotracheal tube suction. RELEVANCE TO CLINICAL PRACTICE: The ESAT(c) is the
      first validated tool to systematically guide endotracheal nursing practice for
      the "inexperienced" nurse.

PMID- 29345014
TI  - Concise Review: Human Induced Pluripotent Stem Cell Models of Retinitis
      Pigmentosa.
AB  - Hereditary retinal dystrophies, specifically retinitis pigmentosa (RP) are
      clinically and genetically heterogeneous diseases affecting primarily retinal
      cells and retinal pigment epithelial cells with blindness as a final outcome.
      Understanding the pathogenicity behind these diseases has been largely precluded
      by the unavailability of affected tissue from patients, large genetic
      heterogeneity and animal models that do not faithfully represent some human
      diseases. A landmark discovery of human induced pluripotent stem cells (hiPSCs)
      permitted the derivation of patient-specific cells. These cells have unlimited
      self-renewing capacity and the ability to differentiate into RP-affected cell
      types, allowing the studies of disease mechanism, drug discovery, and cell
      replacement therapies, both as individual cell types and organoid cultures.
      Together with precise genome editing, the patient specific hiPSC technology
      offers novel strategies for targeting the pathogenic mutations and design
      therapies toward retinal dystrophies. This study summarizes current hiPSC-based
      RP models and highlights key achievements and challenges of these cellular
      models, as well as questions that still remain unanswered. Stem Cells 2018;36:474
      481.

PMID- 29345015
TI  - Dynamic sex chromosomes in Old World chameleons (Squamata: Chamaeleonidae).
AB  - Much of our current state of knowledge concerning sex chromosome evolution is
      based on a handful of 'exceptional' taxa with heteromorphic sex chromosomes.
      However, classifying the sex chromosome systems of additional species lacking
      easily identifiable, heteromorphic sex chromosomes is indispensable if we wish to
      fully understand the genesis, degeneration and turnover of vertebrate sex
      chromosomes. Squamate reptiles (lizards and snakes) are a potential model clade
      for studying sex chromosome evolution as they exhibit a suite of sex-determining
      modes yet most species lack heteromorphic sex chromosomes. Only three (of 203)
      chameleon species have identified sex chromosome systems (all with female
      heterogamety, ZZ/ZW). This study uses a recently developed method to identify sex
      specific genetic markers from restriction site-associated DNA sequence (RADseq)
      data, which enables the identification of sex chromosome systems in species
      lacking heteromorphic sex chromosomes. We used RADseq and subsequent PCR
      validation to identify an XX/XY sex chromosome system in the veiled chameleon
      (Chamaeleo calyptratus), revealing a novel transition in sex chromosome systems
      within the Chamaeleonidae. The sex-specific genetic markers identified here will
      be essential in research focused on sex-specific, comparative, functional and
      developmental evolutionary questions, further promoting C. calyptratus' utility
      as an emerging model organism.

PMID- 29345016
TI  - Evaluation of the implementation of a 24-hr stroke thrombolysis emergency
      treatment for patients with acute ischaemic stroke.
AB  - AIMS AND OBJECTIVES: To assess the trends of intravenous (IV) thrombolysis with
      recombinant tissue plasminogen activator (rt-PA) among patients with acute
      ischaemic stroke (AIS) admitted to our hospital between 2012-2014 and investigate
      the effects of a 24-hr stroke thrombolysis emergency treatment on the
      intrahospital clinical data and outcomes of these patients treated with IV rt-PA
      thrombolysis. BACKGROUND: Although prenotification of stroke by emergency medical
      services has been endorsed by the national recommendations and implemented in
      some developed countries, the development in China is limited. DESIGN: A
      retrospective, single-centre, observational study. METHODS: Patients with AIS
      admitted to our hospital between January 2012-December 2014 were included; those
      who received IV rt-PA thrombolysis within 4.5 hr of onset were investigated.
      Demographic characteristics, including age and sex, and clinical data and
      outcomes, including onset-to-treatment time (OTT), door-to-needle time (DNT),
      premorbid modified Rankin Scale score and proportion of patients treated per
      year, were all recorded. RESULTS: The proportion of patients with AIS who
      received thrombolytic therapy within 4.5 hr increased from 2012-2014. The
      baseline characteristics of all patients were similar. Since the implementation
      of 24-hr stroke thrombolysis emergency treatment in 2013, the median DNT
      significantly decreased in 2014 after implementation (42 min) compared with that
      in 2012 before implementation (81 min) (p < .05). Moreover, the admission-to
      imaging time (37 vs. 33 vs. 36 min) and OTT (176 vs. 147 vs. 124 min)
      significantly decreased during the 3 years (p < .05). CONCLUSIONS: The 24-hr
      stroke thrombolysis emergency treatment reduced in-hospital delay before
      thrombolytic therapy but had no effect on the functional outcomes of the patients
      with AIS. RELEVANCE TO CLINICAL PRACTICE: This study provides opportunities to
      improve the experiences in using 24-h stroke thrombolysis emergency treatment in
      patients with AIS in clinical practice.

PMID- 29345017
TI  - Effects of nutritional support on short-term clinical outcomes and immune
      response in unresectable locally advanced oesophageal squamous cell carcinoma.
AB  - This retrospective study investigated the efficiency of nutritional support in
      unresectable locally advanced oesophageal squamous cell carcinoma (LAOSCC)
      patients who received concurrent chemoradiotherapy (CCRT) based on 5-fluorouracil
      and cisplatin. In the routine care group, 63 patients served as historical
      controls and received nutrition support in a reactive manner. In addition, 57
      patients in the nutritional support group received timely diet counselling, oral
      nutritional supplements, enteral nutrition and/or parenteral nutrition during
      CCRT. This support was based on scores from nutritional risk screening 2002 (NRS
      2002) after June 2014. The nutritional support group had significant advantages
      over the routine care group with respect to the incidence of neutropenia, the
      objective response rate, the change in serum albumin and the lengths of hospital
      stay. In addition, the nutritional support group had significantly higher levels
      of IgG and IL-2, higher proportions of NK, CD3+ and CD4+ cells as well as a
      higher ratio of CD4+ /CD8+ cells than the routine care group (p < .05). In
      contrast, the nutritional support group had a significantly lower level of IL-6.
      In conclusion, the current nutritional care programme could bring benefits of
      improving treatment compliance, reducing toxicity and lengths of hospital stay
      and enhancing the immune response.

PMID- 29345018
TI  - An Orphan Protist Quadricilia rotundata Finally Finds Its Phylogenetic Home in
      Cercozoa.
AB  - Quadricilia rotundata is a heterotrophic flagellate with four flagella. However,
      because this species has no clear morphological characteristics or molecular data
      affiliating it with any known group, Q. rotundata has been treated as a protist
      incertae sedis, for a long time. Here, we established a clonal culture of Q.
      rotundata and sequenced its 18S rDNA sequence. Molecular phylogenetic analysis
      successfully placed Q. rotundata in an environmental clade within Cercozoa, which
      contributes to expand the morphological and species diversity within Cercozoa. We
      also discuss morphological evolution within Cercozoa based on this finding.

PMID- 29345019
TI  - A vascular mechanism to explain thermally mediated variations in deep-body
      cooling rates during the immersion of profoundly hyperthermic individuals.
AB  - NEW FINDINGS: What is the central question of this study? Does the cold-water
      immersion (14 degrees C) of profoundly hyperthermic individuals induce reductions
      in cutaneous and limb blood flow of sufficient magnitude to impair heat loss
      relative to the size of the thermal gradient? What is the main finding and its
      importance? The temperate-water cooling (26 degrees C) of profoundly hyperthermic
      individuals was found to be rapid and reproducible. A vascular mechanism
      accounted for that outcome, with temperature-dependent differences in cutaneous
      and limb blood flows observed during cooling. Decisions relating to cooling
      strategies must be based upon deep-body temperature measurements that have
      response dynamics consistent with the urgency for cooling. ABSTRACT:
      Physiologically trivial time differences for cooling the intrathoracic viscera of
      hyperthermic individuals have been reported between cold- and temperate-water
      immersion treatments. One explanation for that observation is reduced convective
      heat delivery to the skin during cold immersion, and this study was designed to
      test both the validity of that observation, and its underlying hypothesis. Eight
      healthy men participated in four head-out water immersions: two when
      normothermic, and two after exercise-induced, moderate-to-profound hyperthermia.
      Two water temperatures were used within each thermal state: temperate (26 degrees
      C) and cold (14 degrees C). Tissue temperatures were measured at three deep-body
      sites (oesophagus, auditory canal and rectum) and eight skin surfaces, with
      cutaneous vascular responses simultaneously evaluated from both forearms (laser
      Doppler flowmetry and venous-occlusion plethysmography). During the cold
      immersion of normothermic individuals, oesophageal temperature decreased relative
      to baseline (-0.31 degrees C over 20 min; P < 0.05), whilst rectal temperature
      increased (0.20 degrees C; P < 0.05). When rendered hyperthermic, oesophageal (
      0.75 degrees C) and rectal temperatures decreased (-0.05 degrees C) during the
      transition period (<8.5 min, mostly in air at 22 degrees C), with the former
      dropping to 37.5 degrees C only 54 s faster when immersed in cold rather than in
      temperate water (P < 0.05). Minimal cutaneous vasoconstriction occurred during
      either normothermic immersion, whereas pronounced constriction was evident during
      both immersions when subjects were hyperthermic, with the colder water eliciting
      a greater vascular response (P < 0.05). It was concluded that the rapid
      intrathoracic cooling of asymptomatic, hyperthermic individuals in temperate
      water was a reproducible phenomenon, with slower than expected cooling in cold
      water brought about by stronger cutaneous vasoconstriction that reduced
      convective heat delivery to the periphery.

PMID- 29345020
TI  - A new approach in exploring satisfaction with nursing care by nurses themselves.
AB  - AIMS AND OBJECTIVES: To examine the level of satisfaction with nursing care from
      nurses' perspectives, as patients and/or as caregivers for hospitalised
      relatives. BACKGROUND: Many studies that have examined patients' satisfaction
      with nursing care in Jordan and worldwide found high ratings of satisfaction with
      nursing care among patients. These ratings may be inflated because patients, as
      the recipients of care, are often unequipped to judge specific aspects of care,
      unless the patient is also a nurse. METHODS: A descriptive cross-sectional design
      was used. Data were collected using the Patients Satisfaction with Nursing Care
      Quality Questionnaire. The total sample size was 231 registered nurses from eight
      hospitals in Jordan. All participating nurses had either experienced
      hospitalisation for a minimum of 24 hr for themselves or as caregivers for one of
      their close relatives, currently or within the last year. RESULTS: The average
      age of participants was 31.7 (SD = 0.40) years. Most of the participants were
      female with <10 years of work experience. The average score for the level of
      satisfaction was 2.96 of 5, which reflects a moderate level of satisfaction with
      nursing care. None of the 19 items of the satisfaction scale exceeded the
      moderate level. The highest mean score of satisfaction level was 3.20 (SD = 1.17)
      for the skills and competence of nurses, while the lowest mean score was 2.68
      (1.22) for the coordination of care after discharge. CONCLUSION: Nurses as
      patients and/or caregivers evaluated the nursing care during their
      hospitalisation differently in comparison with public patients. The findings
      indicated that nurses perceived only moderate levels of satisfaction when
      undergoing experiences of hospitalisation. RELEVANCE TO CLINICAL PRACTICE: The
      findings from this study may help nurses to become more alert for meeting the
      patients' needs as desired under the best practice.

PMID- 29345021
TI  - Effects of loneliness on illness perception in persons with a chronic disease.
AB  - AIM AND OBJECTIVES: To determine the effects of loneliness on illness perception
      in persons with a chronic disease. BACKGROUND: How an illness is perceived not
      only affects all dimensions of a person's life but also plays an important role
      in his/her coping with the complications and consequences of the disease. One of
      the factors that influence the illness perception is loneliness. DESIGN: The
      study is a descriptive study. METHODS: The study sample included 206 individuals
      over the 18 years of age, conscious, having had a chronic illness at least 1
      year, having no communication problems and agreeing to participate in the study
      after being informed about the study. Data were collected with the Personal
      Information Form, the Illness Perception Questionnaire and the University of
      California Los Angeles Loneliness Scale. The forms were administered to the
      participants in an unoccupied patient room, and the data were collected through
      face-to-face interviews. RESULTS: The results of the study revealed that
      individuals with a chronic disease perceived emotional symptoms accompanying the
      disease more intensely that they accepted their disease was a chronic one and
      that their personal control and treatment control of the disease were at a middle
      level. The mean score the participants obtained from the University of California
      Los Angeles Loneliness Scale was 38.49 +/- 11.15. There was a significant
      negative correlation between this mean score and the mean scores obtained from
      the following subscales consequences, treatment control, illness perception and
      emotional representations. CONCLUSION: In this study, it was concluded that the
      participants perceived their loneliness level as moderate and that their illness
      perception was negatively affected as their loneliness levels increased.
      RELEVANCE TO CLINICAL PRACTICE: The knowledge of clinical nurses about perception
      of patients with chronic illnesses and conditions affecting that perception will
      enhance compliance with the illness management or treatment strategies. Clinical
      nurses should observe residents closely for signs of depression and loneliness
      and support their sense of coherence to reduce emotional and social loneliness.

PMID- 29345023
TI  - The narrow treatment road to survival: Everyday life perspectives of women with
      breast cancer from Iraq and the former Yugoslavia undergoing radiation therapy in
      Sweden.
AB  - This study aimed at exploring how women from Iraq and the former Yugoslavia,
      diagnosed with breast cancer and living in Sweden, experience their everyday life
      during radiation therapy. A qualitative research design was used comprising
      interviews with ten women, five originating from Iraq and five from the former
      Yugoslavia. Striving to survive, the women experienced their everyday life during
      radiation therapy as extremely challenging. This experience can be placed into
      three categories: strategies for survival, keeping up appearances and staying in
      control. Because of these specific challenges, immigrant women may need
      additional information and guidance in conjunction with the diagnosis, which may
      enable them to identify possible sources of support from those closest to them.
      Also, greater attention should focus on acknowledging the woman behind the
      diagnosis, regardless of her origin, to develop an individualised support
      programme to help her cope with everyday life during radiation therapy.

PMID- 29345022
TI  - Seroprevalence of Helicobacter pylori in Korea: A multicenter, nationwide study
      conducted in 2015 and 2016.
AB  - BACKGROUND: The Korean College of Helicobacter and Upper Gastrointestinal
      Research has studied Helicobacter pylori (H. pylori) prevalence since 1998 and
      found a dynamic change in its prevalence in Korea. The aim of this study was to
      determine the recent H. pylori prevalence rate and compare it with that of
      previous studies according to socioeconomic variables. METHODS: We planned to
      enroll 4920 asymptomatic Korean adults from 21 centers according to the
      population distribution of seven geographic areas (Seoul, Gyeonggi, Gangwon,
      Chungcheong, Kyungsang, Cholla, and Jeju). We centrally collected serum and
      tested H. pylori serum IgG using a chemiluminescent enzyme immunoassay. RESULTS:
      We analyzed 4917 samples (4917/4920 = 99.9%) from January 2015 to December 2016.
      After excluding equivocal serologic results, the H. pylori seropositivity rate
      was 51.0% (2414/4734). We verified a decrease in H. pylori seroprevalence
      compared with previous studies performed in 1998, 2005, and 2011 (P < .0001). The
      H. pylori seroprevalence rate differed by area: Cholla (59.5%), Chungcheong
      (59.2%), Kyungsang (55.1%), Jeju (54.4%), Gangwon (49.1%), Seoul (47.4%), and
      Gyeonggi (44.6%). The rate was higher in those older than 40 years (38.1% in
      those aged 30-39 years and 57.7% in those aged 40-49 years) and was lower in city
      residents than in noncity residents at all ages. CONCLUSIONS: Helicobacter pylori
      seroprevalence in Korea is decreasing and may vary according to population
      characteristics. This trend should be considered to inform H. pylori-related
      policies.

PMID- 29345024
TI  - Being Pluripotent, Bone Marrow Very Small Embryonic-Like Stem Cells Rather Than
      Hematopoietic Stem Cells Have the Potential to Regenerate Other Adult Organs.

PMID- 29345025
TI  - The Royal Commission into child sexual abuse: A beginning, not an end.

PMID- 29345026
TI  - Male-male aggression is unlikely to stabilize a poison frog polymorphism.
AB  - Phenotypic polymorphism is common in animals, and the maintenance of multiple
      phenotypes in a population requires forces that act against homogenizing drift
      and selection. Male-male competition can contribute to the stability of a
      polymorphism when males compete primarily with males of the same phenotype. In
      and around a contact zone between red and blue lineages of the poison frog
      Oophaga pumilio, we used simulated territorial intrusions to test the
      nonexclusive predictions that males would direct more aggression towards males of
      (i) their own phenotype and/or (ii) the phenotype that is most common in their
      population. Males in the monomorphic red and blue populations that flank the
      contact zone were more aggressive towards simulated intruders that matched the
      local coloration. However, males in the two polymorphic populations biased
      aggression towards neither their own colour nor the colour most common in their
      population. In sympatry, the rarer colour morph gains no advantage via reduced
      male-male aggression from territorial males in these O. pumilio populations, and
      so male aggression seems unlikely to stabilize colour polymorphism on its own.
      More broadly, these results suggest that the potential for divergent male
      aggression biases to maintain phenotypic diversity depends on the mechanism(s)
      that generate the biases and the degree to which these mechanisms persist in
      sympatry.

PMID- 29345027
TI  - Does flavoured dentifrice increase fluoride intake compared with regular
      toothpaste in children? A systematic review and meta-analysis.
AB  - BACKGROUND: Toothpaste manufacturers encourage through aggressive marketing
      strategies the overconsumption of fluoridated dentifrices. There are conflicting
      results regarding fluoride intake from toothpastes in children. AIM: The aim of
      this systematic review and meta-analysis was to determine whether dentifrice
      flavour increases fluoride ingestion by children. DESIGN: We included clinical
      trials on children that evaluated the use of flavoured dentifrice - FD vs regular
      dentifrice - RD to identify the fluoride intake. An electronic search was
      performed in PubMed, Web of Science, Scopus, The Cochrane Library, LILACS/BBO,
      and grey literature followed by manual search. The methodological quality of the
      studies was assessed using the Cochrane Collaboration common scheme for bias and
      ROBINS-I tool. Data were analysed in subgroups such as low (G1) and ordinary (G2)
      fluoride concentrations of dentifrices. We carried out heterogeneity and
      sensitive analyses. RESULTS: For G1, the fluoride intake from RD was
      significantly higher than from FD [standardised mean difference = -2.57 (-3.26, 
      1.89), P < 0.00001]. For G2, the fluoride ingestion from RD was significantly
      higher than from FD [mean difference = -0.00 (-0.00, -0.00), P = 0.02].
      CONCLUSIONS: There is evidence to support the null hypothesis that flavouring
      from dentifrice does not increase fluoride intake in young children.

PMID- 29345028
TI  - Should we reserve big gun antimanic drugs for only big gun manias?

PMID- 29345029
TI  - High prevalence and functional effects of serum antineuronal antibodies in
      patients with gastrointestinal disorders.
AB  - BACKGROUND: Antineuronal antibodies can be associated with both gastrointestinal
      (GI) and brain disorders. For example, antibodies against the potassium channel
      subunit dipeptidyl-peptidase-like protein-6 (DPPX) bind to neurons in the central
      nervous system (CNS) and myenteric plexus and cause encephalitis, commonly
      preceded by severe unspecific GI symptoms. We therefore investigated the
      prevalence of antineuronal antibodies indicative of treatable autoimmune CNS
      etiologies in GI patients. METHODS: Serum samples of 107 patients (Crohn's
      disease n = 42, ulcerative colitis n = 16, irritable bowel syndrome n = 13,
      others n = 36) and 44 healthy controls were screened for anti-DPPX and further
      antineuronal antibodies using immunofluorescence on rat brain and intestine and
      cell-based assays. Functional effects of high-titer reactive sera were assessed
      in organ bath and Ussing chamber experiments and compared to non-reactive patient
      sera. KEY RESULTS: Twenty-one of 107 patients (19.6%) had antibodies against the
      enteric nervous system, and 22 (20.6%) had anti-CNS antibodies, thus
      significantly exceeding frequencies in healthy controls (4.5% each). Screening on
      cell-based assays excluded established antienteric antibodies. Antibody-positive
      sera were not associated with motility effects in organ bath experiments.
      However, they induced significant, tetrodotoxin (TTX)-insensitive secretion in
      Ussing chambers compared to antibody-negative sera. CONCLUSIONS & INFERENCES:
      Antineuronal antibodies were significantly more frequent in GI patients and
      associated with functional effects on bowel secretion. Future studies will
      determine whether such antibodies indicate patients who might benefit from
      additional antibody-directed therapies. However, well-characterized encephalitis
      related autoantibodies such as against DPPX were not detected, underlining their
      rarity in routine cohorts.

PMID- 29345030
TI  - Reproductive status-dependent kisspeptin and RFamide-related peptide (Rfrp) gene
      expression in female Damaraland mole-rats.
AB  - Damaraland mole rats (Fukomys damarensis) are cooperatively breeding,
      subterranean mammals that exhibit a high reproductive skew. Reproduction is
      monopolised by the dominant female of the group, whereas subordinates are
      physiologically suppressed to the extent that they are anovulatory. In these
      latter animals, it is assumed that normal gonadotropin-releasing hormone
      secretion from the hypothalamus is disrupted. The RFamide peptides kisspeptin
      (Kiss1) and RFamide-related peptide-3 (RFRP-3) are considered as potent
      regulators of gonadotropin release. To assess whether these neuropeptides are
      involved in the mechanism of reproductive suppression, we investigated the
      distribution and gene expression of Kiss1 and Rfrp by means of in situ
      hybridisation in wild-caught female Damaraland mole-rats with different
      reproductive status. In both reproductive phenotypes, substantial Kiss1
      expression was found in the arcuate nucleus and only few Kiss1-expressing cells
      were detected in the anteroventral periventricular nucleus (AVPV), potentially as
      a result of low circulating oestradiol concentrations in breeding and nonbreeding
      females. Rfrp gene expression occurred in the dorsomedial nucleus, the
      paraventricular nucleus and the periventricular nucleus. While in female breeders
      and nonbreeders, plasma oestradiol levels were low and not significantly
      different, quantification of the hybridisation signal for both genes revealed
      significant differences in relation to reproductive status. Reproductively active
      females had more Kiss1-expressing cells and a higher number of silver grains per
      cell in the arcuate nucleus compared to nonreproductive females. This difference
      was most pronounced in the caudal part of the nucleus. No such differences were
      found in the AVPV. Furthermore, breeding status was associated with a reduced
      number of Rfrp-expressing cells in the anterior hypothalamus. This reproductive
      status-dependent expression pattern of Kiss1 and Rfrp suggests that both
      neuropeptides play a role in the regulation of reproduction in Damaraland mole
      rats. Enhanced long-term negative feedback effects of oestradiol could be
      responsible for the lower Kiss1 expression in the arcuate nucleus of
      reproductively suppressed females.

PMID- 29345031
TI  - Amazon drought and forest response: Largely reduced forest photosynthesis but
      slightly increased canopy greenness during the extreme drought of 2015/2016.
AB  - Amazon droughts have impacted regional ecosystem functioning as well as global
      carbon cycling. The severe dry-season droughts in 2005 and 2010, driven by
      Atlantic sea surface temperature (SST) anomaly, have been widely investigated in
      terms of drought severity and impacts on ecosystems. Although the influence of
      Pacific SST anomaly on wet-season precipitation has been well recognized, it
      remains uncertain to what extent the droughts driven by Pacific SST anomaly could
      affect forest greenness and photosynthesis in the Amazon. Here, we examined the
      monthly and annual dynamics of forest greenness and photosynthetic capacity when
      Amazon ecosystems experienced an extreme drought in 2015/2016 driven by a strong
      El Nino event. We found that the drought during August 2015-July 2016 was one of
      the two most severe meteorological droughts since 1901. Due to the enhanced solar
      radiation during this drought, overall forest greenness showed a small increase,
      and 21.6% of forests even greened up (greenness index anomaly >=1 standard
      deviation). In contrast, solar-induced chlorophyll fluorescence (SIF), an
      indicator of vegetation photosynthetic capacity, showed a significant decrease.
      Responses of forest greenness and photosynthesis decoupled during this drought,
      indicating that forest photosynthesis could still be suppressed regardless of the
      variation in canopy greenness. If future El Nino frequency increases as projected
      by earth system models, droughts would result in persistent reduction in Amazon
      forest productivity, substantial changes in tree composition, and considerable
      carbon emissions from Amazon.

PMID- 29345032
TI  - MiRNA-320a inhibits trophoblast cell invasion by targeting estrogen-related
      receptor-gamma.
AB  - AIM: MicroRNAs (miRs) play an essential role in the modulation of trophoblast
      function. We explored miR-320a expression in the human placenta. In addition, we
      report the promising effect and target functional loop of miR-320a in
      trophoblasts. METHODS: MiR-320a expression was investigated in both pre-eclamptic
      and healthy placenta tissues by quantitative real time-polymerase chain reaction
      to determine how miR-320a affected invasion, proliferation and migration in
      trophoblasts. A lipopolysaccharide (LPS) model was established in trophoblasts to
      reveal how LPS supplementation stimulated miR-320a expression. Western blot was
      applied to measure protein expression, which was involved in pathways modulated
      by miR-320a in pre-eclamptic placentas. RESULTS: MiR-320a expression was enhanced
      in the placental specimens of pre-eclamptic patients. Excessive miR-320a
      expression remarkably suppressed trophoblast invasion but did not affect
      migration or proliferation. However, transfection with miR-320a inhibitor
      reinforced trophoblast invasion in vitro. Luciferase assays verified that
      estrogen-related receptor-gamma (ERRgamma) served as a direct target of miR-320a.
      Quantitative real-time polymerase chain reaction and Western blot demonstrated
      that excessive miR-320a expression downregulated ERRgamma transcription and
      translation. Additionally, LPS supplementation showed excessive miR-320a
      expression and ERRgamma downregulation. Impaired ERRgamma and enhanced miR-320a
      expression occurred in PE placentas compared to controls. Pearson correlation and
      linear regression analysis revealed that miR-320a expression was negatively
      related to ERRgamma expression in normal and pre-eclamptic placentas.
      CONCLUSIONS: These findings indicate that miR-320a overexpression causes
      anomalous placentation by targeting ERRgamma. Our research reveals the promising
      effect of miR-320a and the ERRgamma functional loop on placentation.

PMID- 29345033
TI  - Total Synthesis and Conformational Study of Callyaerin A: Anti-Tubercular Cyclic
      Peptide Bearing a Rare Rigidifying (Z)-2,3- Diaminoacrylamide Moiety.
AB  - The first synthesis of the anti-TB cyclic peptide callyaerin A (1), containing a
      rare (Z)-2,3-diaminoacrylamide bridging motif, is reported. Fmoc-formylglycine
      diethylacetal was used as a masked equivalent of formylglycine in the synthesis
      of the linear precursor to 1. Intramolecular cyclization between the
      formylglycine residue and the N-terminal amine in the linear peptide precursor
      afforded the macrocyclic natural product 1. Synthetic 1 possessed potent anti-TB
      activity (MIC100 =32 MUm) while its all-amide congener was inactive. Variable
      temperature NMR studies of both the natural product and its all-amide analogue
      revealed the extraordinary rigidity imposed by this diaminoacrylamide unit on
      peptide conformation. The work reported herein pinpoints the intrinsic role that
      the (Z)-2,3-diaminoacrylamide moiety confers on peptide bioactivity.

PMID- 29345034
TI  - Precipitation frequency alters peatland ecosystem structure and CO2 exchange:
      Contrasting effects on moss, sedge, and shrub communities.
AB  - Climate projections forecast a redistribution of seasonal precipitation for much
      of the globe into fewer, larger events spaced between longer dry periods, with
      negligible changes in seasonal rainfall totals. This intensification of the
      rainfall regime is expected to alter near-surface water availability, which will
      affect plant performance and carbon uptake. This could be especially important in
      peatland systems, where large stores of carbon are tightly coupled to water
      surpluses limiting decomposition. Here, we examined the role of precipitation
      frequency on vegetation growth and carbon dioxide (CO2 ) balances for communities
      dominated by a Sphagnum moss, a sedge, and an ericaceous shrub in a cool
      temperate poor fen. Field plots and laboratory monoliths received one of three
      rainfall frequency treatments, ranging from one event every three days to one
      event every 14 days, while total rain delivered in a two-week cycle and the
      entire season to each treatment remained the same. Separating incident rain into
      fewer but larger events increased vascular cover in all peatland communities:
      vascular plant cover increased 6* in the moss-dominated plots, nearly doubled in
      the sedge plots, and tripled in the shrub plots in Low-Frequency relative to High
      Frequency treatments. Gross ecosystem productivity was lowest in moss communities
      receiving low-frequency rain, but higher in sedge and shrub communities under the
      same conditions. Net ecosystem exchange followed this pattern: fewer events with
      longer dry periods increased CO2 flux to the atmosphere from the moss while
      vascular plant-dominated communities became more of a sink for CO2 . Results of
      this study suggest that changes to rainfall frequency already occurring and
      predicted to continue will lead to increased vascular plant cover in peatlands
      and will impact their carbon-sink function.

PMID- 29345035
TI  - Pressure and pipes: from neuroimaging to virtual measurement.

PMID- 29345036
TI  - Application of molecular tools to elucidate the microbiota of seafood.
AB  - The aim of this review is to present the methodologies currently applied to
      identify microbiota and pathogens transmitted to humans through seafood
      consumption, focusing on molecular techniques and pointing out their importance,
      advantages, disadvantages and applicability. Knowledge of available techniques
      allows researchers to identify which technique best fits their expectations. With
      such discernment, it will be possible to infer which disadvantages will be
      present and, therefore, not interfering with the final result. Two methodologies
      can be employed for this purpose, dependent and independent cultures. However,
      the dependent culture has certain limitations that can be solved through the
      independent cultivation techniques, such as PCR, PFGE and NGS, especially through
      the sequencing of the 16S rRNA region, providing a complete view of microbial
      diversity. These have revolutionized microbiological knowledge, mainly because
      they allow for the identification of uncultivable micro-organisms, which
      represent a substantial portion of total micro-organisms, making it possible to
      elucidate not yet described taxa which may display pathogenic potential, besides
      quantifying microbial communities, microbiota genetics, translated proteins and
      produced metabolites. In addition, transcriptomic and metabolomic techniques also
      allow for the evaluation of possible impacts that microbial communities may
      create in their environment, as well as the determination of potential
      pathogenicity to humans.

PMID- 29345037
TI  - Prevalence of cognitive impairment in major depression and bipolar disorder.
AB  - OBJECTIVES: The current study examines prevalence of cognitive impairment in four
      mood disorder samples, using four definitions of impairment. The impact of
      premorbid IQ on prevalence was examined, and the influence of treatment response.
      METHODS: Samples were: (i) 58 inpatients in a current severe depressive episode
      (unipolar or bipolar), (ii) 69 unmedicated outpatients in a mild to moderate
      depressive episode (unipolar or bipolar), (iii) 56 outpatients with bipolar
      disorder, in a depressive episode, and (iv) 63 outpatients with bipolar disorder,
      currently euthymic. Cognitive assessment was conducted after treatment in Studies
      1 (6 weeks of antidepressant treatment commenced on admission) and 2 (16-week
      course of cognitive behaviour therapy or schema therapy), allowing the impact of
      treatment response to be assessed. All mood disorder samples were compared with
      healthy control groups. RESULTS: The prevalence of cognitive impairment was
      highest for the inpatient depression sample (Study 1), and lowest for the
      outpatient depression sample (Study 2). Substantial variability in rates was
      observed depending on the definition of impairment used. Correcting cognitive
      performance for premorbid IQ had a significant impact on the prevalence of
      cognitive impairment in the inpatient depression sample. There was minimal
      evidence that treatment response impacted on prevalence of cognitive impairment,
      except in the domain of psychomotor speed in inpatients. CONCLUSIONS: As
      interventions aiming to improve cognitive outcomes in mood disorders receive
      increasing research focus, the issue of setting a cut-off level of cognitive
      impairment for screening purposes becomes a priority. This analysis demonstrates
      important differences in samples likely to be recruited depending on the
      definition of cognitive impairment and begins to examine the importance of
      premorbid IQ in determining who is impaired.

PMID- 29345038
TI  - Electrocatalytic Activity of a 2D Phosphorene-Based Heteroelectrocatalyst for
      Photoelectrochemical Cells.
AB  - Research into efficient synthesis, fundamental properties, and potential
      applications of phosphorene is currently the subject of intense investigation.
      Herein, solution-processed phosphorene or few-layer black phosphorus (FL-BP)
      sheets are prepared using a microwave exfoliation method and used in
      photoelectrochemical cells. Based on experimental and theoretical (DFT) studies,
      the FL-BP sheets are found to act as catalytically active sites and show
      excellent electrocatalytic activity for triiodide reduction in dye-sensitized
      solar cells. Importantly, the device fabricated based on the newly designed
      cobalt sulfide (CoSx ) decorated nitrogen and sulfur co-doped carbon nanotube
      heteroelectrocatalyst coated with FL-BP (FL-BP@N,S-doped CNTs-CoSx ) displayed an
      impressive photovoltaic efficiency of 8.31 %, outperforming expensive platinum
      based cells. This work paves the way for using phosphorene-based electrocatalysts
      for next-generation energy-storage systems.

PMID- 29345039
TI  - Successful treatment in a case of ultra-rapid cycling bipolar disorder is
      reflected in brain arousal regulation.

PMID- 29345040
TI  - Assessing and addressing cognitive impairment in bipolar disorder: the
      International Society for Bipolar Disorders Targeting Cognition Task Force
      recommendations for clinicians.
AB  - OBJECTIVES: Cognition is a new treatment target to aid functional recovery and
      enhance quality of life for patients with bipolar disorder. The International
      Society for Bipolar Disorders (ISBD) Targeting Cognition Task Force aimed to
      develop consensus-based clinical recommendations on whether, when and how to
      assess and address cognitive impairment. METHODS: The task force, consisting of
      19 international experts from nine countries, discussed the challenges and
      recommendations in a face-to-face meeting, telephone conference call and email
      exchanges. Consensus-based recommendations were achieved through these exchanges
      with no need for formal consensus methods. RESULTS: The identified questions
      were: (I) Should cognitive screening assessments be routinely conducted in
      clinical settings? (II) What are the most feasible screening tools? (III) What
      are the implications if cognitive impairment is detected? (IV) What are the
      treatment perspectives? Key recommendations are that clinicians: (I) formally
      screen cognition in partially or fully remitted patients whenever possible, (II)
      use brief, easy-to-administer tools such as the Screen for Cognitive Impairment
      in Psychiatry and Cognitive Complaints in Bipolar Disorder Rating Assessment, and
      (III) evaluate the impact of medication and comorbidity, refer patients for
      comprehensive neuropsychological evaluation when clinically indicated, and
      encourage patients to build cognitive reserve. Regarding question (IV), there is
      limited evidence for current evidence-based treatments but intense research
      efforts are underway to identify new pharmacological and/or psychological
      cognition treatments. CONCLUSIONS: This task force paper provides the first
      consensus-based recommendations for clinicians on whether, when, and how to
      assess and address cognition, which may aid patients' functional recovery and
      improve their quality of life.

PMID- 29345041
TI  - Serum amyloid A, procalcitonin, highly sensitive C reactive protein and tumor
      necrosis factor alpha levels and acute inflammatory response in patients with
      hemolysis, elevated liver enzymes, low platelet count (HELLP) and eclampsia.
AB  - AIM: The aim of this study was to determine the relationship between serum
      amyloid A (SAA), procalcitonin (ProC), highly sensitive C reactive protein
      (hsCRP) and tumor necrosis factor (TNF) alpha activity in patients with pre
      eclampsia, eclampsia and hemolysis, elevated liver enzymes, low platelet count
      (HELLP), and the pathogenesis and severity of the disease. METHOD: Ninety
      patients at >= 32 gestational weeks, according to the last date of menstruation
      and ultra-sonographic measurements, diagnosed with pre-eclampsia (30 patients),
      eclampsia (30 patients) or HELLP syndrome (30 patients) were included in the
      study. Thirty healthy pregnant women from the outpatient clinic during the same
      period were recruited as the control. The age, gravida, parity, gestational age,
      systolic and diastolic blood pressures, proteinuria, hemoglobin, thrombocyte
      count, liver function tests (aspartate aminotransferase, alanine
      aminotransferase, lactate dehydrogenase, SAA, TNF alpha, ProC and hsCRP levels
      during pregnancy) were determined and recorded. RESULTS: No statistically
      significant differences were detected between the four groups in terms of age,
      gravida, parity, gestational age and hemoglobin parameters (P > 0.05). When
      compared to the control, systolic and diastolic blood pressures, spot and 24 h
      urine protein levels, aspartate aminotransferase, alanine aminotransferase,
      lactate dehydrogenase, SAA, ProC, hsCRP and TNF alpha levels were significantly
      high and thrombocyte levels were low in the pre-eclamptic, eclamptic and HELLP
      groups (P < 0.05). CONCLUSION: The investigated parameters were useful to gain an
      understanding of the maternal inflammatory profile of pre-eclampsia and might be
      beneficial as markers to predict complications such as HELLP and eclampsia and to
      provide the necessary preventive approach in these patients.

PMID- 29345042
TI  - A systematic review of community-based interventions for the treatment of
      adolescents with overweight and obesity.
AB  - Adolescent obesity is a risk factor for obesity and other chronic disease in
      adulthood. Evidence for the effectiveness of community-based obesity treatment
      programs for adolescents is required to inform policy and clinical decisions.
      This systematic review aims to evaluate recent effective and scalable community
      based weight management programs for adolescents (13-17 years) who are overweight
      or obese. Eight databases (Medline, Embase, PsycINFO, CINAHL, Cochrane Central
      Register of Controlled Trials, Cochrane Database of Systematic Reviews, Informit,
      and Scopus) were searched for studies published between January 2011-2 March 2017
      which are scalable in a community setting and reported primary outcome measures
      relating to weight. Following deduplication, 10,074 records were screened by
      title/abstract with 31 publications describing 21 programs included in this
      review. Programs were heterogeneous in nature (including length, number and
      frequency of sessions, parent-involvement and technology involvement). Reduction
      in adolescent BMIz ranged from 2 to 9% post-program and from 2 to 11% after
      varied lengths of follow-up. Study quality varied (n = 5 weak; n = 8 moderate; n
      = 8 high), and findings are limited by the risk of selection and retention bias
      in the included studies. Factors including the effectiveness and acceptability to
      the target population must be considered when selecting such community programs.

PMID- 29345043
TI  - Termiticidal activity of chitosan against the subterranean termites
      Reticulitermes flavipes and Reticulitermes virginicus.
AB  - BACKGROUND: Chitosan is a derivative form of chitin, which is the major component
      of exoskeletons of arthropods and the cell walls of fungi. The antimicrobial
      activity of chitosan against lepidopterans, aphids, fungi and bacteria has been
      extensively investigated, but only one report on the termiticidal effect of
      chitosan on termites has been published. In this study, we examined the
      termiticidal activity of chitosan by exposing single colonies of Reticulitermes
      flavipes (Kollar) and Reticulitermes virginicus Banks to wood treated with six
      different concentrations of chitosan solutions. Termite mortality and percent
      mass loss of wood samples after exposure to termites for 4 weeks were calculated.
      RESULTS: High termite mortality (>= 94%) occurred during exposure of R. flavipes
      termites to chitosan-treated wood with >=38 mg g-1 treatment concentrations (>=
      2% chitosan), while <50% termite mortality was observed at lower treatment
      concentrations (11-15 mg g-1 ; 0.5% and 1% chitosan). For R. virginicus, 100%
      mortality was observed at all levels of treatment concentrations. A decrease in
      the percent mass loss of the wood sample was apparent in samples treated with
      solutions with an increasing chitosan concentration, with a significant
      difference (P < 0.05) between lower and higher treatment concentrations.
      Treatment retention in wood samples upon leaching was also determined and showed
      retention levels of between 0 and 30 mg g-1 chitosan retention. CONCLUSION: This
      study investigated the exposure of subterranean termites to chitosan as a wood
      preservative. The results show that chitosan treatments at sufficiently high
      loadings could protect wood against termites, preferably under non-leaching
      conditions. (c) 2018 Society of Chemical Industry.

PMID- 29345044
TI  - Pre-clinical Characterization of Absorption, Distribution, Metabolism and
      Excretion Properties of TAK-063.
AB  - TAK-063 is currently being developed to treat schizophrenia. In this study, we
      investigated the absorption, distribution, metabolism and excretion (ADME)
      properties of TAK-063 using several paradigms. Following oral administration of
      TAK-063 at 0.3 mg/kg, bioavailability of TAK-063 was 27.4% in rats and 49.5% in
      dogs with elimination half-lives of 3.1 hr in rats and 3.7 hr in dogs. TAK-063 is
      a highly permeable compound without P-glycoprotein (P-gp) or breast cancer
      resistance protein substrate liability and can be readily absorbed into systemic
      circulation via the intestine. TAK-063 can also cross the blood-brain barrier.
      TAK-063 was metabolized mainly by CYP2C8 and CYP3A4/5, while incubation with
      human liver microsomes produced the major human metabolite, M-I as well as
      several unknown minor metabolites. Metabolism of TAK-063 to M-I occurs through
      hydroxylation of the mono-substituted pyrazole moiety. In vitro, TAK-063 was
      observed to inhibit CYP2C8, CYP2C19 and P-gp with IC50 values of 8.4, 12 and 7.13
      MUM, respectively. TAK-063 was primarily excreted in the faeces in rats and dogs
      with M-I as a predominant component. The pre-clinical data from these ADME
      studies demonstrate a favourable pharmacokinetic profile for TAK-063 with good
      brain distribution supporting the feasibility of targeting central nervous system
      regions involved in schizophrenia pathophysiology. TAK-063 has recently been
      investigated in a phase 2 clinical trial (NCT02477020).

PMID- 29345045
TI  - The in vitro release of cytokines and growth factors from fibrin membranes
      produced through horizontal centrifugation.
AB  - Platelet-rich fibrin membranes are biomaterials widely used for therapeutic
      purposes, and canonically produced through the processing of peripheral blood
      with fixed-angle rotor centrifuges. In this work, we evaluate the in vitro
      stability and release of cytokines and growth factors when these biomaterials are
      produced with a horizontal swing-out clinical centrifuge. Membranes produced from
      the blood of 14 donors were morphologically evaluated by scanning electron
      microscopy and fluorescence microscopy, and their stability was assessed by
      photographic recording after incubation in culture medium for up to 28 days. The
      release of 27 cytokines and growth factors was monitored for three weeks through
      a multiparametric immunoassay. The fibrin membranes presented complex three
      dimensional structure with a high density of nucleated cells. A large release of
      growth factors [platelet derived growth factor, fibroblastic growth factor
      (bFGF), and vascular endothelial growth factor] was detected in the first 24 h,
      followed by time-dependent decay, maintaining significant concentrations after
      three weeks. Both anti-inflammatory and pro-inflammatory cytokines presented
      different release peaks, maintaining high rates of elution for up to 21 days.
      Chemokines of relevance in tissue repair [RANTES, granulocyte colony-stimulating
      factor (G-CSF)] were also produced in large quantities throughout the
      experimental period. The present results demonstrate that blood-derived fibrin
      membranes with high structural stability and cell content can be generated by
      horizontal centrifugation, being able of a prolonged production/release of growth
      factors and pro- and anti-inflammatory cytokines. (c) 2018 Wiley Periodicals,
      Inc. J Biomed Mater Res Part A: 106A: 1373-1380, 2018.

PMID- 29345046
TI  - Standardizing dose in dosimetric bronchial challenge tests.
AB  - Recent technical recommendations on bronchial challenge testing aim at
      standardized assessment of provocative dose of causing 20% decrease in FEV1
      (PD20). The aim of this study was to investigate the effect of mode of
      nebulization on the output of a computerized dosimeter (APS) and to compare PD20
      obtained by two different dosimetric systems in vivo. The output of the APS
      system was tested during continuous nebulization, and using simulated breaths,
      for intermittent actuations with four different durations. Using output data, a
      modified methacholine challenge protocol was applied for APS and compared with a
      standard set-up using Spira dosimeter in 14 asthmatic patients attending
      duplicate methacholine challenges using both systems, within median (range) 3 (1
      6) days apart. The calculated output (mg min-1 ) with all the intermittent mode
      settings was significantly higher (P<0.001) than in the continuous mode, and in
      the intermittent mode, the output was dependent of the pulse duration. The PD20
      values assessed with the APS and Spira systems were significantly correlated (r =
      0.69; P<0.007), without systematic difference in the geometric means (P = 0.10).
      A moderate to good agreement was found for assessment of significant
      hyperresponsiveness. The results suggest that in dosimetric systems for bronchial
      challenge tests, the output of the nebulizer is dependent on the mode of
      nebulization, and this should be considered when standardizing the dose between
      devices and protocols. As long as the delivered dose is determined for the
      specified nebulization mode of the protocol, it may be possible to obtain
      comparable results between different devices.

PMID- 29345047
TI  - Effects of maternal heart sounds on pain and comfort during aspiration in preterm
      infants.
AB  - AIM: This study aimed to evaluate the effects of providing prerecorded maternal
      heart sounds on the level of pain and comfort that are experienced by preterm
      infants during aspiration. METHODS: This was a randomized controlled trial.
      Preterm infants (N = 62) who were receiving care or treatment at a neonatal
      intensive care unit were eligible for participation in this study. Infants in the
      intervention group (n = 32) were provided with prerecorded maternal heart sounds
      before, during, and after aspiration, whereas the infants in the control group (n
      = 30) received routine care. For the collection of the data, the "Preterm Infant
      Information Form" was used to record natal and postnatal information of the
      preterm infant, the "Premature Infant Pain Profile," assessed the level of pain,
      and the "Premature Infant Comfort Scale," assessed the level of comfort. RESULTS:
      There was a significant difference observed between the groups' pain levels
      during aspiration; however, the difference was not significant before and after
      aspiration. Furthermore, there was a significant difference observed between the
      groups' comfort levels prior to aspiration before and during aspiration; however,
      the difference was not significant after aspiration. CONCLUSION: Intervention
      with maternal heart sounds during aspiration effectively reduced pain and
      provided comfort to the premature infants.

PMID- 29345048
TI  - Urinary incontinence type, symptoms, and quality of life: A comparison between
      grand multipara and non-grand multipara women aged >=50 years.
AB  - AIM: Parity and age are risk factors for urinary incontinence (UI). The aim of
      this study was to compare grand multipara women (GMP) to non-grand multipara
      (NGMP) women concerning UI types (stress urinary incontinence [SUI], urge urinary
      incontinence [UUI]), symptoms, and quality of life. METHODS: This correlation
      comparative study used three tools: a demographic/health questionnaire,
      Questionnaire for Urinary Incontinence Diagnosis (QUID), and Incontinence Quality
      of Life (I-QOL). RESULTS: The sample included 132 women, from 50-88 years of age:
      65 NGMP women (mean age: 67.23 years) and 67 GMP women (mean age: 65.04 years).
      The GMP group had a higher score, compared to the NGMP group, for UI type (by
      QUID) and a lower QOL (by I-QOL) , with none of the scores found to be
      statistically significant. By dividing the sample into age groups, 50-59 and >=60
      years, the interaction between the parity and the age groups was found to be
      significant for both the SUI and UUI. CONCLUSION: The innovation of this study is
      the in-depth insight into the association between parity and age regarding UI
      type.

PMID- 29345049
TI  - Cryolipolysis for the treatment of submental fat: Review of the literature.
AB  - BACKGROUND: Submental fat accumulation is a common cosmetic concern.
      Cryolipolysis utilizes noninvasive cooling to lyse adipocytes. A cryolipolysis
      device was recently approved for treatment of submental fat. OBJECTIVE: This
      manuscript provides a review of the preclinical work and clinical trials related
      to cryolipolysis for the treatment of submental fat. Settings, efficacy, and side
      effects are also discussed. MATERIALS AND METHODS: A literature search was
      performed through Pubmed, EMBASE, Web of Science, and CINAHL, using the search
      terms "cryolipolysis," "submental," and "paradoxical adipose hyperplasia".
      Additional sources from the original source bibliographies were used to further
      supplement this review. RESULTS: There are 4 clinical trials and one case series
      (total 101 patients) that evaluated the use of cryolipolysis for treatment of
      submental fat. In these studies, there was a statistically significant reduction
      in submental fat and patients expressed high satisfaction with the treatment.
      Adverse effects were mild and transient. CONCLUSIONS: Cryolipolysis is a
      noninvasive cooling technique that is safe and effective for treatment of
      submental fat. To date, there are no reports of marginal mandibular nerve injury
      or paradoxical adipose hyperplasia following treatment with this device.

PMID- 29345050
TI  - Metabolic alterations in a rat model of hepatic ischaemia reperfusion injury: In
      vivo hyperpolarized 13 C MRS and metabolic imaging.
AB  - BACKGROUND & AIMS: Despite a number of studies addressing the pathophysiology of
      hepatic IRI, a gold standard test for early diagnosis and evaluation of IRI
      remains elusive. This study investigated the metabolic alterations in a rat model
      of hepatic IRI using the in vivo hyperpolarized 13C MRS and metabolic imaging.
      METHODS: Hyperpolarized 13 C MRS with IVIM-DWI was performed on the liver of 7
      sham-operated control rats and 7 rats before and after hepatic IRI. RESULTS: The
      hepatic IRI-induced rats showed significantly higher ratios of [1-13 C]
      alanine/pyruvate, [1-13 C] alanine/tC, [1-13 C] lactate/pyruvate and [1-13 C]
      lactate/tC compared with both sham-operated controls and rats before IRI, whereas
      [1-13 C] pyruvate/tC ratio was decreased in IRI-induced rats. In IVIM-DWI study,
      apparent diffusion coefficient (ADC), f and D values in rats after hepatic IRI
      were significantly lower than those of rats before IRI and sham-operated
      controls. The levels of [1-13 C] alanine and [1-13 C] lactate were negatively
      correlated with ADC, f and D values, whereas the level of [1-13 C] pyruvate was
      positively correlated with these values. CONCLUSIONS: The levels of [1-13 C]
      alanine, [1-13 C] lactate and [1-13 C] pyruvate in conjunction with IVIM-DWI will
      be helpful to evaluate the hepatic IRI as well as these findings can be useful in
      understanding the biochemical mechanism associated with hepatic damage.

PMID- 29345051
TI  - MiR-595 Suppresses the Cellular Uptake and Cytotoxic Effects of Methotrexate by
      Targeting SLC19A1 in CEM/C1 Cells.
AB  - The human solute carrier family 19 member 1 (SLC19A1) is the gene coding for
      reduced folate carrier 1 (RFC1). In our previous work, we showed that the miR-595
      related polymorphism, rs1051296 G>T, which was located in the 3'-untranslated
      region (3'-UTR) of SLC19A1, was associated with high methotrexate (MTX) plasma
      concentrations in patients with paediatric acute lymphoblastic leukaemia (ALL).
      This study aimed to investigate the role of miR-595 in the regulation of SLC19A1
      expression and its effects on the cellular uptake and cytotoxicity of MTX in ALL
      CEM/C1 cells. Luciferase reporter assay was performed to validate SLC19A1 as a
      miR-595 target. RFC1 protein expression was determined via Western blotting.
      Intracellular MTX concentrations were measured by enzyme-linked immunosorbent
      assay (ELISA). Cell viability and apoptosis were assessed using Cell Counting Kit
      8 (CCK-8) assay and flow cytometer, respectively. Compared to the negative
      control, miR-595 mimics induced a significant decrease in the relative luciferase
      activity by binding to the 3'-UTR of SLC19A1 harbouring the rs1051296 T allele (p
      < 0.01). Treatment of CEM/C1 cells with miR-595 mimics substantially reduced RFC1
      protein expression, intracellular MTX levels, MTX-induced cytotoxicity and
      apoptosis rates compared to those of negative control. However, opposite results
      were observed in cells transfected with a miR-595 inhibitor. These findings
      suggested that miR-595 acts as a phenotypic regulator of MTX sensitivity in
      CEM/C1 cells by targeting SLC19A1. This study helped us to understand the
      mechanisms underlying the variable MTX responses observed in patients with ALL.

PMID- 29345052
TI  - HpaP, a novel regulatory protein with ATPase and phosphatase activity,
      contributes to full virulence in Xanthomonas campestris pv. campestris.
AB  - The ability of the bacterial phytopathogen Xanthomonas campestris pv. campestris
      (Xcc) to cause disease is dependent on the type III secretion system (T3SS).
      Proteins of the Xcc T3SS are encoded by hrp (hypersensitive response and
      pathogenicity) genes and whose expression is mainly controlled by the regulators
      HrpG and HrpX. Here, we describe the identification and characterization of a
      previously unknown regulatory protein (named HpaP), which plays important role in
      hrp gene expression and virulence in Xcc. Clean deletion of hpaP demonstrated
      reduced virulence and HR (hypersensitive response) induction of Xcc and
      alterations in cell motility and stress tolerance. Global transcriptome analyses
      revealed that most hrp genes were down regulated in the hpaP mutant, suggesting
      HpaP positively regulates hrp genes. GUS activity assays implied that HpaP
      regulates the expression of hrp genes via controlling the expression of hrpX.
      Biochemical analyses revealed that HpaP protein had both ATPase and phosphatase
      activity. While further site-directed mutagenesis of conserved residues in the
      PTP loop (a protein tyrosine phosphatase signature) of HpaP resulted in the loss
      of both phosphatase activity and regulatory activity in virulence and HR. Taken
      together, the findings identify a new regulatory protein that controls hrp gene
      expression and virulence in Xcc.

PMID- 29345053
TI  - Naringenin (4,5,7-trihydroxyflavanone) suppresses the development of precancerous
      lesions via controlling hyperproliferation and inflammation in the colon of
      Wistar rats.
AB  - Colon cancer is a world-wide health problem and one of the most dangerous type of
      cancer, affecting both men and women. Naringenin (4, 5, 7-trihydroxyflavanone) is
      one of the major flavone glycoside present in citrus fruits. Naringenin has long
      been used in Chinese's traditional medicine because of its exceptional
      pharmacological properties and non-toxic nature. In the present study, we
      investigated the chemopreventive potential of Naringenin against 1,2
      dimethyhydrazine (DMH)-induced precancerous lesions, that is, aberrant crypt foci
      (ACF) and mucin depleted foci (MDF), and its role in regulating the oxidative
      stress, inflammation and hyperproliferation, in the colon of Wistar rats. Animals
      were divided into five groups. In groups 3-5, Naringenin was administered at the
      dose of 50 mg/kg b. wt. orally while in groups 2-4, DMH was administered
      subcutaneously in the groin at the dose of 20 mg/kg b. wt. once a week for first
      5 weeks and animals were euthanized after 10 weeks. Administration of Naringenin
      ameliorated the development of DMH-induced lipid peroxidation, ROS formation,
      precancerous lesions (ACF and MDF) and it also reduced the infiltration of mast
      cells, suppressed the immunostaining of NF-kappaB-p65, COX-2, i-NOS PCNA and Ki
      67 Naringenin treatment significantly attenuated the level of TNF-alpha and it
      also prevented the depletion of the mucous layer. Our findings suggest that
      Naringenin has strong chemopreventive potential against DMH-induced colon
      carcinogenesis but further studies are warranted to elucidate the precise
      mechanism of action of Naringenin.

PMID- 29345054
TI  - Isoflurane anesthesia in aged mice and effects of A1 adenosine receptors on
      cognitive impairment.
AB  - AIMS: Isoflurane may not only accelerate the process of Alzheimer's disease (AD),
      but increase the risk of incidence of postoperative cognitive dysfunction (POCD).
      However, the underlying mechanisms remain unknown. This study was designed to
      investigate whether isoflurane contributed to the POCD occurrence through A1
      adenosine receptor (A1AR) in aged mice. METHODS: We assessed cognitive function
      of mice with Morris water maze (MWM) and then measured expression level of two AD
      biomarkers (P-tau and Abeta) and a subtype of the NMDA receptor (NR2B) in aged
      wild-type (WT) and homozygous A1 adenosine receptor (A1AR) knockout (KO) mice at
      baseline and after they were exposed to isoflurane (1.4% for 2 hours). RESULTS:
      For cognitive test, WT mice with isoflurane exposure performed worse than the WT
      mice without isoflurane exposure. However, A1AR KO mice with isoflurane exposure
      performed better than WT mice with isoflurane exposure. WT mice exposed to
      isoflurane had increased levels of Abeta and phosphorylated tau (P-tau). Levels
      of Abeta and P-tau were decreased in A1AR KO mice, whereas no differences were
      noted between KO mice with and without isoflurane exposure. NR2B expression was
      inversely related to that of P-tau, with no differences found between KO mice
      with and without isoflurane exposure. CONCLUSIONS: We found an association
      between isoflurane exposure, impairment of spatial memory, decreasing level of
      NR2B, and increasing levels of A-beta and P-tau, presumably via the activation of
      the A1A receptor.

PMID- 29345055
TI  - Npas4 deficiency interacts with adolescent stress to disrupt prefrontal GABAergic
      maturation and adult cognitive flexibility.
AB  - Healthy cognitive and emotional functioning relies on a balance between
      excitatory and inhibitory neurotransmission in the prefrontal cortex (PFC). This
      balance is largely established during early postnatal and adolescent
      developmental periods by maturation of the gamma-aminobutyric acid (GABA) system,
      including increased density of parvalbumin (PV) cells and perineuronal nets
      (PNNs). Genetic and/or environmental factors during adolescence can disrupt
      GABAergic maturation and lead to behavioral dysfunction in adulthood. The present
      study examined the interaction between chronic mild stress during adolescence and
      genetic deficiency of neuronal Per-Arnt-Sim domain 4 (Npas4), a brain-specific
      transcription factor that regulates inhibitory neurotransmission and that
      contributes to adolescent prefrontal GABAergic maturation. Male Npas4 wild-type
      (WT) and heterozygous (HET) mice were exposed to adolescent chronic stress and
      tested in adulthood for cognitive function using the attention set shifting task.
      When Npas4 deficiency was combined with adolescent stress, mice displayed
      impaired cognitive flexibility as observed by poor performance on the extra
      dimensional set shift task. At the cellular level, adolescent stress increased
      the percentage of PV cells surrounded by PNNs in the PFC of adult WT animals, an
      effect that was not observed in HET mice. Additionally, Npas4 deficiency and/or
      adolescent stress dysregulated expression of certain GABAergic system markers.
      These results suggest that Npas4 mediates susceptibility to adolescent stress and
      subsequent cognitive functioning and inhibitory tone in adulthood. This shows a
      novel gene by environment interaction related to resilience vs vulnerability to
      stress, with implications for adolescent onset disorders like schizophrenia.

PMID- 29345056
TI  - For when bacterial infections persist: Toll-like receptor-inducible direct
      antimicrobial pathways in macrophages.
AB  - Macrophages are linchpins of innate immunity, responding to invading
      microorganisms by initiating coordinated inflammatory and antimicrobial programs.
      Immediate antimicrobial responses, such as NADPH-dependent reactive oxygen
      species (ROS), are triggered upon phagocytic receptor engagement. Macrophages
      also detect and respond to microbial products through pattern recognition
      receptors (PRRs), such as TLRs. TLR signaling influences multiple biological
      processes including antigen presentation, cell survival, inflammation, and direct
      antimicrobial responses. The latter enables macrophages to combat infectious
      agents that persist within the intracellular environment. In this review, we
      summarize our current understanding of TLR-inducible direct antimicrobial
      responses that macrophages employ against bacterial pathogens, with a focus on
      emerging evidence linking TLR signaling to reprogramming of mitochondrial
      functions to enable the production of direct antimicrobial agents such as ROS and
      itaconic acid. In addition, we describe other TLR-inducible antimicrobial
      pathways, including autophagy/mitophagy, modulation of nutrient availability,
      metal ion toxicity, reactive nitrogen species, immune GTPases (immunity-related
      GTPases and guanylate-binding proteins), and antimicrobial peptides. We also
      describe examples of mechanisms of evasion of such pathways by professional
      intramacrophage pathogens, with a focus on Salmonella, Mycobacteria, and
      Listeria. An understanding of how TLR-inducible direct antimicrobial responses
      are regulated, as well as how bacterial pathogens subvert such pathways, may
      provide new opportunities for manipulating host defence to combat infectious
      diseases.

PMID- 29345057
TI  - Sodium chloride inhibits IFN-gamma, but not IL-4, production by invariant NKT
      cells.
AB  - Invariant NKT (iNKT) cells are a distinct subset of T cells that exert Janus-like
      functions in vivo by producing IFN-gamma and IL-4. Sodium chloride modulates the
      functions of various immune cells, including conventional CD4+ T cells and
      macrophages. However, it is not known whether sodium chloride affects iNKT cell
      function, so we addressed this issue. Sodium chloride inhibited IFN-gamma, but
      not IL-4, production by iNKT cells upon TCR or TCR-independent (IL-12 and IL-18)
      stimulation in a dose-dependent manner. Consistently, sodium chloride reduced the
      expression level of tbx21, but not gata-3, in iNKT cells stimulated with TCR
      engagement or IL-12 + IL-18. Sodium chloride increased phosphorylated p38
      expression in iNKT cells and inhibitors of p38, NFAT5, SGK1, and TCF-1 restored
      IFN-gamma production by iNKT cells stimulated with sodium chloride and TCR
      engagement. Furthermore, adoptive transfer of iNKT cells pretreated with sodium
      chloride restored antibody-induced joint inflammation to a lesser extent than for
      untreated iNKT cells in Jalpha18 knockout mice. These findings suggest that
      sodium chloride inhibits IFN-gamma production by iNKT cells in TCR-dependent and
      TCR-independent manners, which is dependent on p38, NFAT5, SGK1, and TCF-1. These
      findings highlight the functional role of sodium chloride in iNKT cell-mediated
      inflammatory diseases.

PMID- 29345058
TI  - Frontline Science: Anti-PD-L1 protects against infection with common bacterial
      pathogens after burn injury.
AB  - Burn patients are susceptible to infections due, in part, to immune dysfunction.
      Upregulation of programmed death-1 (PD-1) receptor on T cells and programmed cell
      death ligand-1 (PD-L1) on myeloid cells contribute to immune dysfunction in
      nonburn-related sepsis. We hypothesized that PD-1/PDL1 interactions contribute to
      immune dysfunction after burn injury. To determine the impact of burn injury and
      infection on PD-L1, PD-1 and costimulatory receptor expression by leukocytes and
      its relationship to T cell functions. The efficacy of anti-PD-L1 antibody was
      evaluated in a clinically relevant mouse model of burn injury and bacterial
      infection. Mice underwent 35% scald burn followed by Pseudomonas aeruginosa or
      Staphylococcus aureus infection on day 4 postburn. Anti-PD-L1 was administered on
      day 3 postburn. Numbers and phenotype of leukocytes, plasma cytokine
      concentrations, bacterial clearance, organ injury, and survival were assessed.
      Burn injury and infection with P. aeruginosa caused a significant upregulation of
      PD-L1 on myeloid cells, along with a decrease in T cell numbers and function,
      significant multiorgan injury, and decreased survival. Treatment with anti-PD-L1
      antibody improved bacterial clearance, reduced organ injury, and enhanced
      survival during Pseudomonas burn wound infection. Furthermore, anti-PD-L1
      effectively protected against multiorgan injury, and improved bacterial clearance
      and survival following systemic S. aureus infection after burn injury. Blockade
      of PD-1/PD-L1 interactions might represent a viable treatment to improve outcomes
      among critically ill burn-injured subjects and increased leukocyte PD-L1
      expression could serve as a valuable biomarker to select appropriate patients for
      such treatment.

PMID- 29345059
TI  - MicroRNA networks associated with active systemic juvenile idiopathic arthritis
      regulate CD163 expression and anti-inflammatory functions in macrophages through
      two distinct mechanisms.
AB  - Systemic juvenile idiopathic arthritis (SJIA) is a severe childhood arthropathy
      with features of autoinflammation. Monocytes and macrophages in SJIA have a
      complex phenotype with both pro- and anti-inflammatory properties that combine
      features of several well characterized in vitro conditions used to activate
      macrophages. An important anti-inflammatory phenotype is expression of CD163, a
      scavenger receptor that sequesters toxic pro-inflammatory complexes that is
      highly expressed in both active SJIA and macrophage activation syndrome (MAS).
      CD163 is most strongly up-regulated by IL-10 (M(IL-10)), and not by other
      conditions that reflect features seen in SJIA monocytes such as M(LPS+IC).
      MicroRNA plays key roles in integrating cellular signals such as those in
      macrophage polarization, and as such we hypothesize microRNAs regulate macrophage
      functional responses in SJIA including CD163 expression. We find that 2 microRNAs
      previously found to be elevated in active SJIA, miR-125a-5p and miR-181c,
      significantly reduced macrophage CD163 expression through 2 distinct mechanisms.
      Neither microRNA was elevated in M(IL-10) with robust CD163 expression, but were
      instead induced in M(LPS+IC) where they restricted CD163 mRNA expression. Mir-181
      species directly targeted CD163 mRNA for degradation. In contrast, miR-125a-5p
      functions indirectly, as transcriptome analysis of miR-125a-5p overexpression
      identified "cytokine-cytokine receptor interactions" as the most significantly
      repressed gene pathway, including decreased IL10RA, required for IL-10-mediated
      CD163 expression. Finally, overexpression of miR-181c inhibited CD163 anti
      inflammatory responses to hemoglobin or high mobility group box 1 (HMGB1)
      complexes. Together, these data show that microRNA utilizes multiple mechanisms
      to integrate well-characterized polarization phenotypes and regulate macrophage
      functional properties seen in SJIA.

PMID- 29345060
TI  - Porcine NK cells display features associated with antigen-presenting cells.
AB  - NK cells are members of the innate immunity and play a central role in the
      defense against viral infections and cancer development, but also contribute to
      triggering and shaping adaptive immune responses. Human NK cells may express MHC
      II and costimulatory molecules, including CD86, CD80, and OX40 ligand, which
      allows them to stimulate the CD4+ T-cell response. In contrast, murine NK cells
      do not express MHC II or costimulatory molecules. Upon activation, mouse NK cells
      can acquire these molecules from dendritic cells (DCs) via intercellular membrane
      transfer, which leads to suppression of DC-induced CD4+ T-cell responses rather
      than stimulation of T-cell responses. Previous studies showed that porcine NK
      cells can express MHC II molecules, but it was unknown if porcine NK cells also
      express costimulatory molecules and whether NK cells may affect T-cell
      proliferation. We found that primary porcine NK cells express functional MHC II
      molecules and costimulatory CD80/86, particularly upon activation with IL-2/IL
      12/IL-18, and that they are able to stimulate T-cell proliferation. In addition,
      we show that porcine NK cells are able to internalize antigens derived from
      killed target cells in an actin polymerization-dependent process. All together,
      these results indicate that porcine NK cells possess properties associated with
      APCs, which allows them to stimulate T-cell proliferation.

PMID- 29345061
TI  - Monocyte subsets exhibit transcriptional plasticity and a shared response to
      interferon in SIV-infected rhesus macaques.
AB  - The progression to AIDS is influenced by changes in the biology of heterogeneous
      monocyte subsets. Classical (CD14++CD16-), intermediate (CD14++CD16+), and
      nonclassical (CD14+CD16++) monocytes may represent progressive stages of monocyte
      maturation or disparate myeloid lineages with different turnover rates and
      function. To investigate the relationship between monocyte subsets and the
      response to SIV infection, we performed microarray analysis of monocyte subsets
      in rhesus macaques at three time points: prior to SIV infection, 26 days
      postinfection, and necropsy with AIDS. Genes with a 2-fold change between
      monocyte subsets (2023 genes) or infection time points (424 genes) were selected.
      We identify 172 genes differentially expressed among monocyte subsets in both
      uninfected and SIV-infected animals. Classical monocytes express genes associated
      with inflammatory responses and cell proliferation. Nonclassical monocytes
      express genes associated with activation, immune effector functions, and cell
      cycle inhibition. The classical and intermediate subsets are most similar at all
      time points, and transcriptional similarity between intermediate and nonclassical
      monocytes increases with AIDS. Cytosolic sensors of nucleic acids, restriction
      factors, and IFN-stimulated genes are induced in all three subsets with AIDS. We
      conclude that SIV infection alters the transcriptional relationship between
      monocyte subsets and that the innate immune response to SIV infection is
      conserved across monocyte subsets.

PMID- 29345062
TI  - Trans-mission control in the urinary tract: Local cytokine regulation of monocyte
      proliferation to combat infection.

PMID- 29345063
TI  - Immunotherapy: It is not just for cancer anymore.

PMID- 29345064
TI  - TLR8 ligation induces apoptosis of monocytic myeloid-derived suppressor cells.
AB  - Myeloid-derived suppressor cells (MDSCs) accumulate in tumors and the peripheral
      blood of cancer patients and demonstrate cancer-promoting activity across
      multiple tumor types. A limited number of agents are known to impact MDSC
      activity. TLR8 is expressed in myeloid cells. We investigated expression of TLR8
      on MDSC and the effect of a TLR8 agonist, motolimod, on MDSC survival and
      function. TLR8 was highly expressed in monocytic MDSC (mMDSC) but absent in
      granulocytic MDSC (gMDSC). Treatment of human PBMC with motolimod reduced the
      levels of mMDSC in volunteers and cancer donors versus control (P < 0.001).
      Motolimod did not impact levels of gMDSC. The reduction of mMDSC was due to
      induced cell death by TLR8 ligation. Pretreatment of PBMC with a FAS neutralizing
      antibody inhibited motolimod-induced reduction of mMDSC (P < 0.001). Finally, we
      demonstrated that mMDSC impeded IL-2 secretion by CD3/CD28-activated T cells; IL
      2 secretion was partially restored when cells were cocultured with motolimod (142
      +/- 36 pg/ml vs. 59 +/- 13 pg/ml; P = 0.03). There is increasing evidence that
      MDSCs contribute to the progression of cancer by inhibiting tumor-directed T
      cells. TLR8 agonists may synergize with cancer immunotherapeutic approaches to
      enhance the antitumor effects of the adaptive immune response.

PMID- 29345065
TI  - Fingolimod targets cerebral endothelial activation to block leukocyte recruitment
      in the central nervous system.
AB  - Fingolimod (FTY720), an immunomodulator, is approved as an oral treatment for
      patients with relapsing forms of multiple sclerosis. Its effects are largely
      attributed to its mechanism of selectively retaining lymphocytes in the lymph
      nodes to reduce autoreactive T-cell recruitment in the CNS. In this study, we
      investigated the therapeutic effect of FTY720 on an animal model of CNS
      inflammation induced by intracerebral ventricle LPS injection. We found that
      FTY720 treatment significantly prevented LPS-induced neutrophil recruitment in
      the CNS by inhibiting leukocyte recruitment in cerebral microvessels.
      Furthermore, FTY720 also inhibited the expressions of adhesion molecules on the
      cerebral endothelium, but did not affect the expression levels of pro
      inflammatory cytokines (TNF-alpha and IL-6) and chemokines (CXCL1 and CXCL2) in
      the CNS parenchyma. The inhibition of endothelial activation was accompanied by
      reduced phosphorylation of signaling molecules, including serine/threonine
      specific protein kinase (Akt), STAT6, and nuclear factor-kappaB. This FTY720
      attenuated inhibition of leukocyte recruitment and endothelial activation was
      reversed by blocking the functions of sphingosine kinase 2 or sphingosine-1
      phosphate receptor 1. Our study demonstrated, for the first time, that FTY720
      directly inhibits the phosphorylation of multiple signaling molecules in
      endothelial cells, thereby effectively blocking leukocyte recruitment in the CNS.

PMID- 29345066
TI  - Protease activated-receptor 2 is necessary for neutrophil chemorepulsion induced
      by trypsin, tryptase, or dipeptidyl peptidase IV.
AB  - Compared to neutrophil chemoattractants, relatively little is known about the
      mechanism neutrophils use to respond to chemorepellents. We previously found that
      the soluble extracellular protein dipeptidyl peptidase IV (DPPIV) is a neutrophil
      chemorepellent. In this report, we show that an inhibitor of the protease
      activated receptor 2 (PAR2) blocks DPPIV-induced human neutrophil chemorepulsion,
      and that PAR2 agonists such as trypsin, tryptase, 2f-LIGRL, SLIGKV, and AC55541
      induce human neutrophil chemorepulsion. Several PAR2 agonists in turn block the
      ability of the chemoattractant fMLP to attract neutrophils. Compared to
      neutrophils from male and female C57BL/6 mice, neutrophils from male and female
      mice lacking PAR2 are insensitive to the chemorepulsive effects of DPPIV or PAR2
      agonists. Acute respiratory distress syndrome (ARDS) involves an insult-mediated
      influx of neutrophils into the lungs. In a mouse model of ARDS, aspiration of
      PAR2 agonists starting 24 h after an insult reduce neutrophil numbers in the
      bronchoalveolar lavage (BAL) fluid, as well as the post-BAL lung tissue.
      Together, these results indicate that the PAR2 receptor mediates DPPIV-induced
      chemorepulsion, and that PAR2 agonists might be useful to induce neutrophil
      chemorepulsion.

PMID- 29345067
TI  - Supramolecular Gels Derived from the Salts of Variously Substituted Phenylacetic
      Acid and Dicyclohexylamine: Design, Synthesis, Structures, and Dye Adsorption.
AB  - A well-studied supramolecular synthon, namely, secondary ammonium monocarboxylate
      (SAM), was exploited to generate a new series of organic salts derived from
      variously substituted phenylacetic acid and dicyclohexylamine as potential low
      molecular-weight gelators. As much as 25 % of the SAM salts under study were
      gelators. The gels were characterized by rheology, and the morphology of the gel
      networks was studied by high-resolution electron microscopy. Single-crystal and
      powder XRD data were employed to study structure-property (gelation)
      correlations. One of the gels could adsorb a hydrophobic dye (Nile Red) more
      efficiently than that of a hydrophilic dye (Calcein) from dimethyl sulfoxide;
      this might provide useful clues towards the development of stain-removing gels.

PMID- 29345068
TI  - International Diabetes Federation 2017.
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- 29345069
TI  - Automation aided optimization of cloning, expression and purification of enzymes
      of the bacterial sialic acid catabolic and sialylation pathways enzymes for
      structural studies.
AB  - The process of obtaining a well-expressing, soluble and correctly folded
      constructs can be made easier and quicker by automating the optimization of
      cloning, expression and purification. While there are many semiautomated
      pipelines available for cloning, expression and purification, there is hardly any
      pipeline that involves complete automation. Here, we achieve complete automation
      of all the steps involved in cloning and in vivo expression screening. This is
      demonstrated using 18 genes involved in sialic acid catabolism and the surface
      sialylation pathway. Our main objective was to clone these genes into a His
      tagged Gateway vector, followed by their small-scale expression optimization in
      vivo. The constructs that showed best soluble expression were then selected for
      purification studies and scaled up for crystallization studies. Our technique
      allowed us to quickly find conditions for producing significant quantities of
      soluble proteins in Escherichia coli, their large-scale purification and
      successful crystallization of a number of these proteins. The method can be
      implemented in other cases where one needs to screen a large number of
      constructs, clones and expression vectors for successful recombinant production
      of functional proteins.

PMID- 29345070
TI  - Following one's scientific compass.

PMID- 29345071
TI  - Detecting selection signatures on the X chromosome of the Chinese Debao pony.
AB  - The X chromosome shows a special interaction between demographic factors and
      genetic variation, and the analysis of X-linked genomic variation can therefore
      provide insights into the unique effects of demography and selection on the horse
      genome that cannot be readily detected by autosomal markers. Debao (DB) ponies
      have experienced intense selective pressure for the development of their small
      stature (<106 cm at adult height). To identify selective sweeps on the X
      chromosome of the DB pony, we performed a genome-wide scan of three Chinese horse
      breeds using an Equine SNP70 BeadChip. Using Yili and Mongolian horses (>134 cm
      at adult height) as reference groups, both FST and XP-EHH revealed that five
      regions on the X chromosome were under strong selection, resulting in 95
      overlapping genes. Seven of these genes, SMS, PHEX, ACSL4, CHRDL1, CACNA1F, DKC1
      and CDKL5, are involved in bone development, growth hormone secretion and fat
      deposition. The region showing the strongest selection pressure was located at
      the position of 86.6-87.5 Mb. The subsequent genome-wide association analysis of
      the adult height of three Chinese horse breeds detected the two most significant
      SNPs in the same region, and these two SNPs overlapped with the gene CHRDL1. As a
      member of the bone morphogenetic protein (BMP) superfamily, CHRDL1 antagonizes
      the function of BMP4 and plays an important role in embryonic bone formation and
      cartilage generation. Our results provide new insights into the X-linked
      selection in Chinese Debao pony.

PMID- 29345072
TI  - Genetic monitoring of horses in the Czech Republic: A large-scale study with a
      focus on the Czech autochthonous breeds.
AB  - We propose the first comprehensive in-depth study monitoring horses in the Czech
      Republic. We scanned 9,289 animals from 44 populations for 17 equine STRs. Other
      equids analysed involved Equus przewalskii and Equus asinus. The total of 228
      different alleles were detected, with the mean number of 13.4 per locus. The
      highest allelic richness (AR) was found in the Welsh Part Bred (6.01), followed
      by the Camargue (5.93) and Czech Sport Pony (5.91), whereas the Friesian
      exhibited the lowest AR (3.06). Interpopulation differences explained
      approximately nine per cent of the total genetic diversity. Reynold's genetic
      distance ranged from 0.003 between the Czech Warmblood and the Slovak Warmblood
      to 0.404 between the Friesian and donkeys. Close genetic proximity between the
      Silesian Noriker and Noriker was revealed. The Moravian Warmblood was better
      differentiated and more distant from the Czech Warmblood than the Kinsky Horse
      and retained the original genes of the old Austro-Hungarian tribes. A high gene
      flow level and a lack of genetic structure were found in the seven studied
      populations. Despite the historical bottlenecks and previous inbreeding, the
      Czech-Moravian Belgian Horse, Hucul, Old Kladruber Horse and Silesian Noriker did
      not suffer a serious loss of genetic diversity due to genetic drift/low effective
      population size. A NeighborNet dendrogram revealed breeds not classified in their
      groups according to the nomenclature (the Friesian, Hafling and Merens).

PMID- 29345073
TI  - Improving accuracy of genomic prediction in Brangus cattle by adding animals with
      imputed low-density SNP genotypes.
AB  - Reliable genomic prediction of breeding values for quantitative traits requires
      the availability of sufficient number of animals with genotypes and phenotypes in
      the training set. As of 31 October 2016, there were 3,797 Brangus animals with
      genotypes and phenotypes. These Brangus animals were genotyped using different
      commercial SNP chips. Of them, the largest group consisted of 1,535 animals
      genotyped by the GGP-LDV4 SNP chip. The remaining 2,262 genotypes were imputed to
      the SNP content of the GGP-LDV4 chip, so that the number of animals available for
      training the genomic prediction models was more than doubled. The present study
      showed that the pooling of animals with both original or imputed 40K SNP
      genotypes substantially increased genomic prediction accuracies on the ten
      traits. By supplementing imputed genotypes, the relative gains in genomic
      prediction accuracies on estimated breeding values (EBV) were from 12.60% to
      31.27%, and the relative gain in genomic prediction accuracies on de-regressed
      EBV was slightly small (i.e. 0.87%-18.75%). The present study also compared the
      performance of five genomic prediction models and two cross-validation methods.
      The five genomic models predicted EBV and de-regressed EBV of the ten traits
      similarly well. Of the two cross-validation methods, leave-one-out cross
      validation maximized the number of animals at the stage of training for genomic
      prediction. Genomic prediction accuracy (GPA) on the ten quantitative traits was
      validated in 1,106 newly genotyped Brangus animals based on the SNP effects
      estimated in the previous set of 3,797 Brangus animals, and they were slightly
      lower than GPA in the original data. The present study was the first to leverage
      currently available genotype and phenotype resources in order to harness genomic
      prediction in Brangus beef cattle.

PMID- 29345074
TI  - A century later.

PMID- 29345075
TI  - Genetic analyses of linear profiling data on 3-year-old Swedish Warmblood horses.
AB  - A linear profiling protocol was introduced in 2013 at tests for 3-year-old
      Swedish Warmblood horses. In this protocol, traits are subjectively described on
      a nine-point linear scale from one biological extreme to the other. This
      complements the traditional scoring where horses are evaluated in relation to the
      breeding objective. This study aimed to investigate the suitability of the linear
      information for genetic evaluation. Data on 22 conformation traits, 17 movement
      traits, 14 jumping traits and one temperament trait from 3,410 horses tested
      between 2013 and 2016 were analysed using an animal model. For conformation
      traits, the heritabilities ranged from 0.10 for description of hock joint from
      behind to 0.52 for shape of the neck. For movement traits, the highest
      heritability (0.54) was estimated for elasticity in trot and the lowest (0.08)
      for energy in walk. The heritabilities for jumping traits ranged from 0.05 for
      the ability to focus on the assignment to 0.57 for scope. Genetic correlations
      between linear traits and corresponding traditionally scored traits were strong (
      0.37 to in many cases <-0.9). The results show that the linear information is
      suitable for genetic evaluation and can be a useful tool for breeders.

PMID- 29345076
TI  - Rice-farming care for the elderly people with cognitive impairment in Japan: a
      case series.

PMID- 29345077
TI  - Gender difference in the association and presentation of visual hallucinations in
      dementia with Lewy bodies: statistical and methodological issues.

PMID- 29345078
TI  - Re: An investigation of public attitudes towards dementia in Bristol and South
      Gloucestershire using an online version of the Approaches to Dementia
      Questionnaire.

PMID- 29345079
TI  - Acreemagnosia (loss of financial knowledge): a symptom of functional and
      cognitive loss in frail elderly.

PMID- 29345081
TI  - Screening for latent tuberculosis infection among patients with rheumatoid
      arthritis in the era of biologics and targeted synthetic disease-modifying anti
      rheumatic drugs in India, a high-burden TB country: The importance of Mantoux and
      Quantiferon-TB Gold tests.
AB  - AIM: To test the validity of an augmented tuberculosis skin test (a-TST) combined
      with Quantiferon TB-gold(r) (QFTG) test for the screening of latent tuberculosis
      infection (LTBI) in patients with rheumatoid arthritis (RA) being considered for
      treatment with biologic disease-modifying anti-rheumatic drugs or targeted
      synthetic disease-modifying anti-rheumatic drugs. METHOD: Standard TST using 1
      tuberculin unit (TU) of purified protein derivative (PPD, RT23 strain) was
      carried out. If the positivity was less as compared to the general population,
      then a-TST using 10 TU PPD was employed. Simultaneously, QFTG test was also
      performed. RESULTS: Using standard TST, 6/44 (13.6%), patients were positive
      compared to the reported figures of ~ 40% of the general population; 38 of the
      remaining TST-negative patients were then given an a-TST with 10 TU PPD; eight of
      them dropped out. Of the remaining 30 patients, eight (26.6%) were positive.
      Another 70 patients tested directly with a-TST; 22 (31.4%) were found positive.
      Thus, of a total of 100 patients tested with a-TST, 30 (30%) were positive. In 54
      a-TST negative patients, QFTG was done; seven (13%) were positive. Thus, in
      combined a-TST with QFTG, 43% of the RA patients were found positive, suggestive
      of the presence of LTBI. CONCLUSION: Combined a-TST with QFTG testing gave 43%
      positivity among RA patients, which is close to the reported ~ 40% Mantoux
      positivity in the general population. Therefore, this method for the screening of
      LTBI in Indian patients with RA being considered for tumor necrosis factor alpha
      treatment could be satisfactory for offsetting TB flare. It may apply to other
      high-burden TB countries around the world.

PMID- 29345080
TI  - Environmental adaptation and vertical dissemination of ESBL-/pAmpC-producing
      Escherichia coli in an integrated broiler production chain in the absence of an
      antibiotic treatment.
AB  - High prevalence numbers of extended-spectrum beta-lactamase- (ESBL-)/plasmid
      mediated AmpC beta-lactamase- (pAmpC-) producing Escherichia coli in broiler
      chicken and their distribution along the broiler production chain is an ongoing
      problem in food production. We, therefore, investigated resistant isolates along
      the broiler production chain to determine whether there is a constantly occurring
      direct vertical transmission of the ESBL-/pAmpC-producing E. coli from the parent
      flocks to their offspring or not. We, furthermore, analysed the isolates
      concerning the occurrence of virulence factors and their ability to form biofilms
      to estimate their potential to effectively colonize broiler chickens and/or
      persist and survive in the environment of the broiler production facilities.
      Using whole genome sequencing, we could show that ESBL-/pAmpC-producing E. coli
      were likely transferred in a step-wise process along the broiler production chain
      but not directly from the parent flock to the fattening flock with every single
      batch of offspring chickens. Additionally, resistant E. coli strains showing an
      extraintestinal pathogenic genotype as well as high numbers of virulence
      associated genes including the production of curli fibres and cellulose have high
      capabilities to persist and spread in the broiler production chain.

PMID- 29345082
TI  - How should we respond to cannabis-impaired driving?

PMID- 29345083
TI  - Brief workshops to teach drug and alcohol first aid: A pilot evaluation study.
AB  - INTRODUCTION AND AIMS: Health and community service workers frequently encounter
      people with alcohol and other drug (AOD) problems in the course of their work,
      yet few have had training on how to respond effectively. A Drug and Alcohol First
      Aid workshop was developed by Lyndon, a non-government organisation treatment
      provider, and delivered to community and health sector workers and the general
      public. It presented evidence-based information regarding AOD use and harm
      reduction and treatment options. A pilot evaluation of the workshop was conducted
      to assess changes in participants' knowledge about AOD, methods of responding to
      use and attitudes towards individuals who use AOD, over a 3 month period. DESIGN
      AND METHODS: A self-report evaluation survey was developed and administered to
      workshop participants at three time points: before (T1), immediately after (T2)
      and 3 months after the workshop (T3). Paired samples t-tests examined changes in
      knowledge, role adequacy, motivation and personal views. RESULTS: A total of 142
      participants completed the T1 survey, 184 completed the T2 survey and 98
      completed the T3 survey. Between T1 and T2, there were significant increases in
      scores for knowledge and role adequacy, indicating significant improvements in
      these areas. No significant differences were found for motivation and personal
      views. At T3, knowledge and role adequacy scores remained significantly higher
      than at baseline. DISCUSSION AND CONCLUSIONS: Drug and Alcohol First Aid appears
      to be a viable initiative to improve AOD-related knowledge and role adequacy.
      However, alternative strategies may be required to shift negative attitudes
      towards individuals who use AOD. [Kostadinov VR, Roche AM, McEntee A, Allan JM,
      Meumann NR, McLaughlin LL. Brief workshops to teach drug and alcohol first aid: A
      pilot evaluation study. Drug Alcohol Rev 2018;37:23-27].

PMID- 29345084
TI  - The lived experience of autologous stem cell-transplanted patients: Post
      transplantation and before discharge.
AB  - AIMS AND OBJECTIVES: To explore the lived experience of the patients post
      haematopoietic stem cell transplantation and specifically after engraftment and
      before discharge. BACKGROUND: Patients post-stem cell transplantation experience
      significant changes in all life aspects. Previous studies carried out by other
      researchers focused mainly on the postdischarge experience, where patients
      reported their perceptions that have always been affected by the life post
      transplantation and influenced by their surroundings. The lived experience of
      patients, specifically after engraftment and prior to discharge (the "transition"
      phase), has not been adequately explored in the literature. Doing so might
      provide greater insight into the cause of change post-haematopoietic stem cell
      transplantation. DESIGN: This study is a phenomenological description of the
      participants' perception about their lived experience post-haematopoietic stem
      cell transplantation. The study used Giorgi's method of analysis. METHODS:
      Through purposive sampling, 15 post-haematopoietic stem cell transplantation
      patients were recruited. Data were collected by individual interviews. Data were
      then analysed based on Giorgi's method of analysis to reveal the meaning of a
      phenomenon as experienced through the identification of essential themes.
      RESULTS: The analysis process revealed 12 core themes covered by four categories
      that detailed patients lived experience post-haematopoietic stem cell
      transplantation. The four categories were general transplant experience, effects
      of transplantation, factors of stress alleviation and finally life post
      transplantation. CONCLUSION: This study showed how the haematopoietic stem cell
      transplantation affected the patients' physical, psychological and spiritual well
      being. Transplantation also impacted on the patients' way of thinking and
      perception of life. Attending to patients' needs during transplantation might
      help to alleviate the severity of the effects and therefore improve experience.
      RELEVANCE TO CLINICAL PRACTICE: Comprehensive information about transplantation
      needs to be provided over different intervals and at different occasions. The
      role of the haematopoietic stem cell transplantation coordinators is important,
      and their communication skills and knowledge were found to be significant in
      patients' preparation and decision-making. As healthcare providers usually attend
      to only the patients' physical and psychological needs, spirituality was found to
      play an important role in maintaining morale and making sense of the meaning of
      life.

PMID- 29345085
TI  - Effects of ultrasonication variables on the activity and properties of alpha
      amylase preparation.
AB  - Recently, ultrasound was demonstrated to increase enzyme activity in food
      industry. In most studies, an enzyme-substrate mixture was ultrasonicated. Very
      little is reported on the ultrasonication of enzyme preparation; the effects of
      ultrasonication variables on the enzyme activity and properties remained unclear.
      In this study, an alpha-amylase preparation was ultrasonicated under different
      conditions. At the ultrasonic frequency, power, temperature, and time of 20 kHz,
      25 W/mL, 30 degrees C, and 75 s, respectively, the secondary structure of the
      alpha-amylase was changed and that improved the catalytic activity by 47% over
      the control. The optimal temperature and pH of the alpha-amylase preparation did
      not change under the ultrasonic treatment. In addition, ultrasonic treatment
      increased kinetic parameters of the alpha-amylase including maximal velocity Vmax
      , Michaelis constant Km , turnover number Kcat , and catalytic specificity
      constant Kcat /Km . Nevertheless, the ultrasonicated alpha-amylase had lower
      thermal inactivation rate constant and half-life value than the nonultrasonicated
      enzyme. Ultrasonic treatment can be considered as a novel solution for
      improvement in enzyme activity. (c) 2018 American Institute of Chemical Engineers
      Biotechnol. Prog., 34:702-710, 2018.

PMID- 29345086
TI  - Safety of dipyrone (metamizole) in children-What's the risk of agranulocytosis?

PMID- 29345087
TI  - In this issue: February 2018.

PMID- 29345088
TI  - Retraction.
AB  - : 'The association of hypotension with the insertion of an abdominal retractor
      during lower abdominal surgery in pediatric patients: a retrospective
      observational study' by Rika Nakayama, Takahiro Mihara, Yoshihisa Miyamoto & Koui
      Ka.1 The above article from Pediatric Anesthesia, published online on July 7,
      2015 in Wiley Online Library (http://wileyonlinelibrary.com) has been retracted
      by agreement between the authors, the Journal Editor in Chief, Andrew Davidson,
      and John Wiley & Sons Ltd. The retraction has been agreed following a review of
      the study data by the authors, which found that cases not satisfying the
      inclusion criteria were included and that there were data collection errors with
      respect to the patients' ages and sexes. As a result, the authors judged that the
      reproducibility of the results could not be guaranteed and have requested
      retraction. REFERENCE: Nakayama R, Mihara T, Miyamoto Y, Ka K. The association of
      hypotension with the insertion of an abdominal retractor during lower abdominal
      surgery in pediatric patients: a retrospective observational study. Pediatr
      Anesth. 2015;25:824-828. https://doi.org/10.1111/pan.12656.

PMID- 29345089
TI  - Increased lactate load of older red blood cell preparations increases blood
      lactate concentrations in infants during cardiac surgery.

PMID- 29345090
TI  - Comment on Chiem J, Ivanova I, Jimenez N. Anaphylactic reaction to tranexamic
      acid in an adolescent undergoing posterior spinal fusion.

PMID- 29345091
TI  - The responses of microbial temperature relationships to seasonal change and
      winter warming in a temperate grassland.
AB  - Microorganisms dominate the decomposition of organic matter and their activities
      are strongly influenced by temperature. As the carbon (C) flux from soil to the
      atmosphere due to microbial activity is substantial, understanding temperature
      relationships of microbial processes is critical. It has been shown that
      microbial temperature relationships in soil correlate with the climate, and
      microorganisms in field experiments become more warm-tolerant in response to
      chronic warming. It is also known that microbial temperature relationships
      reflect the seasons in aquatic ecosystems, but to date this has not been
      investigated in soil. Although climate change predictions suggest that
      temperatures will be mostly affected during winter in temperate ecosystems, no
      assessments exist of the responses of microbial temperature relationships to
      winter warming. We investigated the responses of the temperature relationships of
      bacterial growth, fungal growth, and respiration in a temperate grassland to
      seasonal change, and to 2 years' winter warming. The warming treatments increased
      winter soil temperatures by 5-6 degrees C, corresponding to 3 degrees C warming
      of the mean annual temperature. Microbial temperature relationships and
      temperature sensitivities (Q10 ) could be accurately established, but did not
      respond to winter warming or to seasonal temperature change, despite significant
      shifts in the microbial community structure. The lack of response to winter
      warming that we demonstrate, and the strong response to chronic warming
      treatments previously shown, together suggest that it is the peak annual soil
      temperature that influences the microbial temperature relationships, and that
      temperatures during colder seasons will have little impact. Thus, mean annual
      temperatures are poor predictors for microbial temperature relationships.
      Instead, the intensity of summer heat-spells in temperate systems is likely to
      shape the microbial temperature relationships that govern the soil-atmosphere C
      exchange.

PMID- 29345092
TI  - Known unknowns: Examining the burden of neurocognitive impairment in the end
      stage renal failure population.
AB  - The burden of neurocognitive impairment (NCI) in patients receiving maintenance
      dialysis represents a spectrum of deficits across multiple cognitive domains that
      are associated with hospitalization, reduced quality-of-life, mortality and
      forced decision-making around dialysis withdrawal. Point prevalence data suggest
      that dialysis patients manifest NCI at rates 3- to 5-fold higher than the general
      population, with executive function the most commonly affected cognitive domain.
      The unique physiology of the renal failure state and maintenance dialysis appears
      to drive an excess of vascular dementia subtype compared to the general
      population where classical Alzheimer's disease predominates. Despite the absence
      of evidence-based cost-effective therapies for NCI, detecting it in this
      population creates opportunity to proactively personalize care through education,
      supported decision making and targeted communication strategies to cover specific
      areas of deficit and help define goals of care. This review discusses NCI in the
      dialysis setting, including developments in the definition of neurocognitive
      impairment, dialysis-specific epidemiology across modalities, screening
      strategies and opportunities for dialysis providers in this space.

PMID- 29345094
TI  - But is it 'evidence'?

PMID- 29345093
TI  - Rapid fabrication of detachable three-dimensional tissues by layering of cell
      sheets with heating centrifuge.
AB  - Confluent cultured cells on a temperature-responsive culture dish can be
      harvested as an intact cell sheet by decreasing temperature below 32 degrees C. A
      three-dimensional (3-D) tissue can be fabricated by the layering of cell sheets.
      A resulting 3-D multilayered cell sheet-tissue on a temperature-responsive
      culture dish can be also harvested without any damage by only temperature
      decreasing. For shortening the fabrication time of the 3-D multilayered
      constructs, we attempted to layer cell sheets on a temperature-responsive culture
      dish with centrifugation. However, when a cell sheet was attached to the culture
      surface with a conventional centrifuge at 22-23 degrees C, the cell sheet hardly
      adhere to the surface due to its noncell adhesiveness. Therefore, in this study,
      we have developed a heating centrifuge. In centrifugation (55g) at 36-37 degrees
      C, the cell sheet adhered tightly within 5 min to the dish without significant
      cell damage. Additionally, centrifugation accelerated the cell sheet-layering
      process. The heating centrifugation shortened the fabrication time by one-fifth
      compared to a multilayer tissue fabrication without centrifugation. Furthermore,
      the multilayered constructs were finally detached from the dishes by decreasing
      temperature. This rapid tissue-fabrication method will be used as a valuable tool
      in the field of tissue engineering and regenerative therapy. (c) 2018 American
      Institute of Chemical Engineers Biotechnol. Prog., 34:692-701, 2018.

PMID- 29345095
TI  - The term will survive.

PMID- 29345096
TI  - Psychiatric sequelae of corticosteroid use in hematology in Australia: A
      qualitative study.
AB  - Despite widespread steroid usage for treating hematological conditions, minimal
      attention focuses on associated psychiatric side-effects. In the present study,
      we examined hematology patients' experiences of high-dose steroid treatment. This
      was undertaken by the use of a qualitative, descriptive design, which included
      convenience sampling and the inductive, cyclic, and constant comparative thematic
      analysis of interview transcripts. Eighteen patients participated, who were
      diagnosed with lymphoma, myeloma, leukemia, or idiopathic thrombocytopenia
      purpura. Four themes emerged: side-effects, misattribution of cause, self
      management, and fragmented information. The study results revealed that
      hematology patients administered steroids can experience negligible to extensive
      erratic side-effects, with severe adverse repercussions. Psychological reactions
      to steroids are often misattributed. Patients mostly self-manage adverse effects
      experienced and receive only fragmented preparatory information, often not
      understanding steroid side-effects. Nurses could provide helpful "in the moment"
      education for inpatients who misunderstood steroid-related adverse effects, such
      as aggressive urges. Adverse repercussions for family were occasionally evident.
      Education, support, and ongoing care for patients experiencing adverse steroid
      side-effects are inadequate. Health professionals need to develop patient- and
      family-centered educational resources for potential, unpredictable, and usually
      adverse steroid side-effects.

PMID- 29345097
TI  - The diagnostic value of the functional lumen imaging probe versus high-resolution
      anorectal manometry in patients with fecal incontinence.
AB  - BACKGROUND: The functional lumen imaging probe (EndoFLIP(r) ) is a new technology
      that measures the distensibility of the anal canal represented by the anal
      distensibility index. The aims of this study were (i) to compare the anal
      distensibility index to anal pressure in a cohort of patients with fecal
      incontinence (FI) and (ii) to compare the diagnostic value of the EndoFLIP(r) to
      that of high-resolution anorectal manometry (HRAM) in the same cohort of
      patients. METHODS: Eighty-three consecutive patients with FI who underwent
      EndoFLIP(r) and HRAM assessments were enrolled. The diagnostic value of the
      EndoFLIP(r) was compared to that of HRAM and agreement between EndoFLIP(r) and
      HRAM data was assessed. KEY RESULTS: More than 70% of the patients diagnosed with
      anal deficiency at rest and/or during voluntary contractions by HRAM had the same
      diagnosis using the EndoFLIP(r) . Two patients with higher distensibility indexes
      at rest had normal anal resting pressures. Sixteen patients with a normal
      EndoFLIP(r) index (ie, normal distensibility index at rest and during voluntary
      contractions) had an abnormal HRAM result. Seven of these 16 patients (44%) had
      no sphincter lesion or neuropathic disorder that could explain an abnormal anal
      sphincter function. CONCLUSIONS & INFERENCES: We demonstrated that the anal
      distensibility index and HRAM results are largely in agreement. We did, however,
      identify several discrepancies between the two techniques, indicating that they
      may be complementary.

PMID- 29345098
TI  - Influence of maternal obesity on fetal growth at different periods of pregnancies
      with normal glucose tolerance.
AB  - AIM: We aimed to examine the influence of maternal obesity on fetal growth in
      utero at different periods of pregnancies with normal glucose tolerance. METHODS:
      A retrospective cohort study on 356 pregnant women with normal glucose tolerance
      was conducted. The women were categorized by pre-pregnancy body mass index (BMI)
      as obese (OB; BMI >= 25.0 kg/m2 ) or non-obese (n-OB). Z-scores of the fetal
      abdominal circumference (AC) and the rate of fetal macrosomia (AC >= 90th
      percentile) at 19, 30, and 36 gestational weeks (GW) were compared between the
      two groups. Maternal demographics (age, parity, height, pre-pregnancy BMI,
      history of prior large-for-gestational-age delivery) were compared between the
      pregnancies with and without fetal macrosomia at each gestational age. Multiple
      logistic regression analysis was performed to determine the independent risk
      factors for fetal macrosomia. RESULTS: Birthweights of the neonates were
      significantly higher in the OB group. Z-scores of the fetal AC were significantly
      higher in the OB group at 30 and 36 GW, while no significant difference was found
      at 19 GW. The rates of fetal macrosomia in the OB group were also higher at 30
      and 36 GW, while maternal obesity was not associated with fetal macrosomia at 19
      GW. Pre-pregnancy BMI was detected as the independent predictor of fetal
      macrosomia at 30 GW (odds ratio, 1.19 [95% CI]) and 36 GW (odds ratio, 1.13 [95%
      CI]). CONCLUSION: Maternal pre-pregnancy obesity has a promoting effect on fetal
      growth from the third trimester through birth.

PMID- 29345099
TI  - Aortic versus carotid intima-media thickness and impact of aortic valve disease.
AB  - BACKGROUND AND AIMS: Intima-media thickness is a marker for atherosclerosis but
      is also influenced by shear stress and flow. We evaluated the relation between
      intima-media thickness of the descending aorta (AoIMT) and the common carotid
      artery (CIMT) in patients with and without severe aortic valve disease (sAVD).
      METHODS: A total of 310 patients (233 with sAVD, 77 without) were examined with
      regard to AoIMT and CIMT using transesophageal echocardiography and carotid
      ultrasound, respectively, before valvular and/or aortic surgery. Digitally stored
      B-mode images were used for semiautomatic AoIMT and CIMT measurements. RESULTS:
      There were no significant differences in patients with or without sAVD with
      regard to AoIMT (1.35 +/- 0.31 vs. 1.35 +/- 0.33 mm) or CIMT (0.80 +/- 0.15 vs.
      0.78 +/- 0.16 mm). The correlations between AoIMT and CIMT were r = 0.29 in
      patients with and r = 0.51 in patients without sAVD, and the difference between
      these correlations was significant (P<0.05). In multivariate regression, age was
      the main determinant for AoIMT and CIMT in both groups, further in sAVD, the
      aortic mean pressure gradient (Pmean ) was a determinant of AoIMT, but not of
      CIMT. CONCLUSIONS: The correlation between CIMT and AoIMT is weaker in patients
      with sAVD compared to those without sAVD. Pmean is also a significant predictor
      of AoIMT, but not of CIMT. This implies that, in addition to the atherosclerotic
      process, turbulent aortic flow or altered blood flow helicity created by large
      stroke volumes and diastolic flow reversal or high-velocity jets, affect the
      intima-media of the descending aorta and common carotid artery differently.

PMID- 29345100
TI  - Relationship between orthodox and traditional medical practitioners in the
      transmission of traditional medical knowledge in Nigeria.
AB  - BACKGROUND: The problem of incomplete transmission of traditional medical
      knowledge to the younger generation is of concern to information professionals
      especially in developing countries where most rural communities depend on
      traditional medicine for primary health care. OBJECTIVE: The purpose of this
      study was to investigate the collaboration between orthodox and traditional
      medical practitioners as well as the implication of the collaboration for
      transmission of traditional medical knowledge in Nigeria. METHOD: Eighteen
      communities were purposively selected from six states in south-western Nigeria.
      Snowball technique was used in selecting 110 traditional medical practitioners.
      Three key informant interviews and two focus group discussion sessions were
      conducted in each state. Data were analysed thematically. DISCUSSION: Results
      showed the existence of a low level of collaboration mainly in the form of
      patient referrals which were not performed officially and mostly one sided. This
      was attributed to the negative perception of traditional medicine by orthodox
      practitioners and the failure of government to give traditional medicine its due
      recognition. This was reportedly responsible for the lack of interest by children
      of traditional medical practitioners to acquire traditional medical knowledge.
      CONCLUSION: The study recommends inclusion of traditional medicine in the health
      policy and educational curriculum from the basic level.

PMID- 29345101
TI  - A Pdgf-cCreERT2 knock-in mouse model for tracing PDGF-C cell lineages during
      development.
AB  - PDGF-C, a member of the platelet-derived growth factor (PDGF) family, plays
      important roles in the development of craniofacial structures, the neural system,
      the vascular system, and tumors. PDGF-C could also be required for the regulation
      of certain types of stem or progenitor cells as suggested by its expression in
      the regions where these cells are located. To further characterize the role of
      PDGF-C in development, we generated a Pdgf-cCreERT2 mouse strain, in which a
      tamoxifen-inducible Cre (CreERT2) cDNA was specifically targeted into the Pdgf-c
      genomic locus and controlled by the endogenous Pdgf-c regulatory elements. We
      also showed that Cre activity in this mouse strain could be specifically induced
      by tamoxifen, which allowed the fate of PDGF-C-expressing cells to be traced at
      various stages of development. Using this model system, we demonstrated for the
      first time that PDGF-C-expressing cells could be multipotent, generating multiple
      cell lineages required for the formation of the cerebellum. Therefore, the Pdgf
      cCreERT2 mouse strain generated in this study will be a valuable transgenic tool
      for exploring the function of PDGF-C in development and stem cell biology.

PMID- 29345102
TI  - The mycobiota of the sand fly Phlebotomus perniciosus: Involvement of yeast
      symbionts in uric acid metabolism.
AB  - The knowledge of the fungal mycobiota of arthropods, including the vectors of
      human and animal diseases, is still limited. Here, the mycobiota associated with
      the sand fly Phlebotomus perniciosus, the main vector of leishmaniasis in the
      western Mediterranean area, by a culture-dependent approach (microbiological
      analyses and sequencing of the 26S rRNA gene), internal transcribed spacer (ITS)
      rRNA amplicon-based next-generation sequencing, fluorescence in situ
      hybridisation (FISH), and genome sequencing of the dominant yeast species was
      investigated. The dominant species was Meyerozyma guilliermondii, known for its
      biotechnological applications. The focus was on this yeast and its prevalence in
      adults, pupae and larvae of reared sand flies (overall prevalence: 57.5%) and of
      field-collected individuals (overall prevalence: 9%) was investigated. Using
      whole-mount FISH and microscopic examination, it was further showed that M.
      guilliermondii colonizes the midgut of females, males and larvae and the distal
      part of Malpighian tubules of female sand flies, suggesting a possible role in
      urate degradation. Finally, the sequencing and analysis of the genome of M.
      guilliermondii allowed predicting the complete uric acid degradation pathway,
      suggesting that the yeast could contribute to the removal of the excess of
      nitrogenous wastes after the blood meal of the insect host.

PMID- 29345103
TI  - Incidence of Common Cancers in Users of Antimuscarinic Medications for Overactive
      Bladder: A Danish Nationwide Cohort Study.
AB  - The purpose of this study was to estimate the incidence rate (IR) of 10 common
      cancers in new users of antimuscarinic overactive bladder (OAB) medications. We
      conducted a cohort study using data recorded in Danish registers for patients
      newly exposed to the OAB drugs, darifenacin, fesoterodine, oxybutynin,
      solifenacin, tolterodine or trospium in years 2004-2012, aged >=18 years and
      without cancer before treatment initiation. We estimated IRs for each study
      cancer (bladder, breast, colorectal, lung, melanoma, non-Hodgkin lymphoma,
      pancreas, prostate, renal and uterine), standardised by age and sex and explored
      IR trends over time since treatment initiation. For all cancer analyses, only the
      first incident targeted cancer was considered. Of 72,917 patients (60% women;
      mean age at treatment start: 66 years), 3475 developed a study cancer during
      259,072 person-years of follow-up. The most common study cancers were prostate
      (48.1% of study cancers in men), breast (40.0% of study cancers in women) and
      lung (15.4% of all study cancers). The overall standardised study cancer IR was
      5.4 per 1000 person-years (95% confidence interval, 5.3-5.6); IRs were similar
      across individual OAB drugs. The standardised IRs for bladder and prostate
      cancers, which have symptoms in common with OAB, were highest in the first 6
      months of treatment initiation and lower thereafter. In contrast, IRs for other
      study cancers were nearly constant during follow-up. Cancer IRs did not vary
      substantially by individual OAB drug. Protopathic bias is a plausible explanation
      for the higher rates of bladder and prostate cancers observed soon after starting
      OAB drug treatment.

PMID- 29345104
TI  - A Self-Growing Strategy for Large-Scale Crystal Assembly Tubes.
AB  - Assembled tubular materials have attracted widespread attention due to their
      potential applications in catalysis, bionics, and optic-electronics. Many
      versatile methods, including template assistance and self-assembly, have been
      developed for fabrication of tubular materials. Here we demonstrate a self
      growing strategy to prepare large-scale crystal assembly tubes. Addition of the
      template and the need for the sophisticated equipment are avoided with this
      method. The sidewall of the tubes is composed of a layer of polyhedral crystals
      that are connected together through grain coalescence. We demonstrate that the
      assembled tubular structure is obtained by the synergetic effect of the
      passivation layer and the dissolution-recrystallization process. This facile one
      step strategy and the formation mechanism will offer guidance for fabrication of
      new superstructures.

PMID- 29345105
TI  - OsGATA7 modulates brassinosteroids-mediated growth regulation and influences
      architecture and grain shape.

PMID- 29345106
TI  - National study of the nutritional status of Korean older adults with dementia who
      are living in long-term care settings.
AB  - AIM: To evaluate the nutritional status of older adults with dementia who were
      living in long-term care settings. METHODS: As a secondary analysis, this study
      used the data from the Nationwide Survey on Dementia Care in Korea that was
      conducted between December 1, 2010, and August 31, 2011, which surveyed 3472
      older adults with dementia, aged >=60 years (mean age: 81.24 years), who were
      residing in 248 randomly selected long-term care settings in South Korea. Twenty
      three different variables that related to the participants' demographics,
      diseases, and functional and nutritional characteristics were selected. The
      nutritional status was assessed by using the Mini Nutritional Assessment (MNA).
      Descriptive statistics, an ANOVA, and a chi-squared test were used to analyze the
      data. RESULTS: The mean MNA score of the participants was 17.90. The malnutrition
      rate was 38.4% (n = 1333), with 54.7% (n = 1900) of the participants at risk for
      malnutrition. The largest population with malnutrition resided in long-term care
      hospitals (47.9%), followed by nursing homes (34.1%), and group homes (25.9%).
      Being older and female, while exhibiting higher cognitive impairment, more
      neuropsychiatric symptoms, higher functional dependency, and a higher number of
      disabilities, were associated with poor nutritional status. CONCLUSION: The
      nutritional status of older adults with dementia who were living in long-term
      care settings in South Korea was poor and associated with multiple factors.
      Paying special attention to recognizing, assessing, preventing, and treating
      malnutrition in this population is necessary.

PMID- 29345107
TI  - Introduction to methodology of dose-response meta-analysis for binary outcome:
      With application on software.
AB  - OBJECTIVE: Dose-response meta-analysis (DRMA) is widely applied to investigate
      the dose-specific relationship between independent and dependent variables. Such
      methods have been in use for over 30 years and are increasingly employed in
      healthcare and clinical decision-making. In this article, we give an overview of
      the methodology used in DRMA. METHODS: We summarize the commonly used regression
      model and the pooled method in DRMA. We also use an example to illustrate how to
      employ a DRMA by these methods. RESULTS: Five regression models, linear
      regression, piecewise regression, natural polynomial regression, fractional
      polynomial regression, and restricted cubic spline regression, were illustrated
      in this article to fit the dose-response relationship. And two types of pooling
      approaches, that is, one-stage approach and two-stage approach are illustrated to
      pool the dose-response relationship across studies. The example showed similar
      results among these models. CONCLUSION: Several dose-response meta-analysis
      methods can be used for investigating the relationship between exposure level and
      the risk of an outcome. However the methodology of DRMA still needs to be
      improved.

PMID- 29345108
TI  - High neutrophil-to-lymphocyte ratio predicts poor prognosis in patients with
      squamous cell carcinoma of the head and neck treated with definitive
      chemoradiotherapy.
AB  - AIM: To evaluate the role of neutrophil-to-lymphocyte ratio as a prognostic
      marker in squamous cell carcinoma of the head and neck treated with definitive
      chemoradiotherapy. METHODS: A retrospective chart review was performed on
      patients presenting to our service between 2001 and 2014. Overall survival (OS)
      and progression-free survival (PFS) were calculated using Kaplan-Meier estimates.
      The association between neutrophil-to-lymphocyte ratio and survival was analyzed
      by both univariate and multivariate analysis. RESULTS: Across all patients, OS
      and PFS at 5 years was 59% and 54%, respectively. Increasing T stage correlated
      with a statistically significant decrease in OS (P  =  0.004) and PFS (P  = 
      0.005). Both overall (P  =  0.003) and PFS (P  =  0.002) were highest in lifetime
      nonsmokers and lowest in current smokers. Patients who commenced treatment in
      2010 or later had a significantly greater overall (P  =  0.014) and PFS (P  = 
      0.009) compared to those treated prior. Patients with p16 negative tumors had a
      significantly lower overall (P < 0.001) and PFS (P < 0.001) compared to those
      with p16 positive tumors. Patients treated with cisplatin had an overall and PFS
      of 66.8% and 59.9% respectively at 5 years. Patients with a neutrophil-to
      lymphocyte ratio of less than 4 at treatment initiation had a significantly
      greater overall (P  =  0.015) and PFS (P  =  0.017). The trend for OS remained
      significant in multivariate analysis (P  =  0.05). CONCLUSION: A high neutrophil
      to-lymphocyte ratio at treatment initiation is a negative predictive marker for
      squamous cell carcinoma of the head and neck treated with definitive
      chemoradiotherapy.

PMID- 29345109
TI  - Effectiveness of smartphone technologies on glycaemic control in patients with
      type 2 diabetes: systematic review with meta-analysis of 17 trials.
AB  - Patient education and behavioural interventions for self-management of type 2
      diabetes mellitus (T2DM) are effective but place demands on manpower resources.
      This systematic review aimed to investigate the effectiveness of smartphone
      technologies (STs) for improving glycaemic control among T2DM patients. CENTRAL,
      MEDLINE, Embase, CINAHL and ScienceDirect were searched through December 2016.
      Randomized controlled trials comparing STs with usual diabetes care among T2DM
      patients and reporting change in glycated haemoglobin (HbA1c) level were
      included. Seventeen trials (2,225 participants) were included. There was a
      significant reduction in HbA1c (pooled weighted mean difference: -0.51%; 95%
      confidence interval: -0.71% to -0.30%; p < 0.001), favouring ST intervention. The
      pooled weighted mean difference was -0.83% in patients with T2DM <8.5 years and 
      0.22% in patients with T2DM >=8.5 years, with significant subgroup difference (p
      = 0.007). No subgroup differences were found among different follow-up durations,
      trial locations, patients' age, healthcare provider contract time, baseline body
      mass index and baseline HbA1c. Compared with usual diabetes care, STs improved
      glycaemic control among T2DM patients, especially for patients at earlier disease
      stages (duration of diagnosis <8.5 years). STs could be a complement or
      alternative to labour-intensive patient education and behavioural interventions,
      but more studies on up-to-date technologies are needed.

PMID- 29345110
TI  - Remarkable similarity in Plasmodium falciparum and Plasmodium vivax
      geranylgeranyl diphosphate synthase dynamics and its implication for antimalarial
      drug design.
AB  - Malaria, mainly caused by Plasmodium falciparum and Plasmodium vivax, has been a
      growing cause of morbidity and mortality. P. falciparum is more lethal than is P.
      vivax, but there is a vital need for effective drugs against both species.
      Geranylgeranyl diphosphate synthase (GGPPS) is an enzyme involved in the
      biosynthesis of quinones and in protein prenylation and has been proposed to be a
      malaria drug target. However, the structure of P. falciparumGGPPS (PfGGPPS) has
      not been determined, due to difficulties in crystallization. Here, we created a
      PfGGPPS model using the homologous P.vivaxGGPPS X-ray structure as a template. We
      simulated the modeled PfGGPPS as well as PvGGPPS using conventional and Gaussian
      accelerated molecular dynamics in both apo- and GGPP-bound states. The MD
      simulations revealed a striking similarity in the dynamics of both enzymes with
      loop 9-10 controlling access to the active site. We also found that GGPP
      stabilizes PfGGPPS and PvGGPPS into closed conformations and via similar
      mechanisms. Shape-based analysis of the binding sites throughout the simulations
      suggests that the two enzymes will be readily targeted by the same inhibitors.
      Finally, we produced three MD-validated conformations of PfGGPPS to be used in
      future virtual screenings for potential new antimalarial drugs acting on both
      PvGGPPS and PfGGPPS.

PMID- 29345111
TI  - Association between hepatitis C infection in Thai patients with oral lichen
      planus: A case-control study.
AB  - AIM: The aim of the present study was to investigate the prevalence of hepatitis
      C virus (HCV) infection and evaluate liver enzyme levels in patients from upper
      northern Thailand with oral lichen planus (OLP). METHODS: A case-control study of
      101 patients with OLP and 101 patients without OLP was conducted. Peripheral
      blood was taken from each patient and screened for anti-HCV antibody using
      immunochromatography. Positive samples were further confirmed using
      chemiluminescent microparticle immunoassay (CMIA) and reverse transcription
      polymerase chain reaction. In addition, liver enzyme levels, alanine
      transaminase, aspartate transaminase, and alkaline phosphatase were evaluated
      using spectrophotometry. RESULTS: Immunochromatography and CMIA revealed that
      nine patients with OLP (8.9%) were positive for anti-HCV antibodies, whereas only
      one patient without OLP was HCV positive (odds ratio = 9.78). All patients who
      were HCV positive had significantly higher liver enzyme levels than patients who
      were HCV negative. CONCLUSIONS: The results of the present study indicated that
      OLP in certain patients was significantly associated with HCV. This could warrant
      screening for HCV-infected patients with OLP in Thailand.

PMID- 29345112
TI  - Low NT-proBNP levels in overweight and obese patients do not rule out a diagnosis
      of heart failure with preserved ejection fraction.
AB  - BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a
      heterogeneous syndrome that presents clinicians with a diagnostic challenge. The
      use of natriuretic peptides to exclude a diagnosis of HFpEF has been proposed. We
      sought to compare HFpEF patients with N-terminal pro-brain natriuretic peptide
      (NT-proBNP) level above and below the proposed cut-off. METHODS: Stable patients
      (n = 30) with left ventricular (LV) ejection fraction >= 50% were eligible if
      they had a diagnosis of HF according to the European Society of Cardiology
      diagnostic criteria. Characteristics of patients with NT-proBNP below (<=125
      pg/mL) and above (>125 pg/mL) the diagnostic criterion were compared. RESULTS:
      There were 19 (66%) women with median age 54 years. Half were African American
      (16, 53%), and most were obese. There were no significant differences in clinical
      characteristics or medication use between groups. LV end-diastolic volume index
      was greater in high NT-proBNP patients (P = 0.03). Left atrial volume index, E/e'
      ratio, and E/e' ratio at peak exercise were not significantly different between
      NT-proBNP groups. Peak oxygen consumption (VO2 ), VO2 at ventilatory threshold,
      and ventilatory efficiency measures were impaired in all patients and were not
      significantly different between high and low NT-proBNP patients. CONCLUSIONS: NT
      proBNP was below the proposed diagnostic cut-off point of 125 pg/mL in half of
      this obese study cohort. Cardiac diastolic dysfunction and cardiorespiratory
      fitness were not significantly different between high and low NT-proBNP patients.
      These data indicate that excluding the diagnosis of HFpEF based solely on NT
      proBNP levels should be discouraged.

PMID- 29345113
TI  - Intervention for childhood obesity based on parents only or parents and child
      compared with follow-up alone.
AB  - OBJECTIVES: The study aims to assess the effects of family-based interventions
      targeted to parents only or to parents-and-child for the prevention and treatment
      of childhood obesity. METHOD: An open-label randomized study was conducted in 247
      children (166 girls, 5-11 years) with body mass index (BMI) in the 85-98th
      percentile. Participants were allocated to three groups: parents-only (n = 89),
      parents-and-child (n = 84) and follow-up alone (n = 74). The intervention
      consisted of 12 once-weekly meetings with a dietician and psychologist. All
      children were followed for 2 years. Changes in anthropometric, clinical and
      lifestyle outcomes were assessed. RESULTS: The 3-month intervention was completed
      by 58 (65.2%) in the parents-only, 61 (72.6%) in the parents-child and 49 (66.2%)
      in the control group (P = .554). BMI-standard deviation score (SDS) decreased
      from baseline to 3 months in both intervention groups (parents-only: from 1.74 +/
      0.31 to 1.66 +/- 0.36, P < .001; parents-child, 1.83 +/- 0.33 to 1.76 +/- 0.36,
      P = .012), with no significant change in the controls (1.73 +/- 0.32 to 1.70 +/-
      0.31, P = .301). The 2-year follow-up was completed by 45 in each of the
      intervention groups (50.5% and 53.5%, respectively) and 37 controls (50%) (P =
      .896). Compared with baseline, only the parents-child group showed a significant
      decrease in BMI-SDS (1.56 +/- 0.46, P = .006). The rate of children who met the
      criteria for metabolic syndrome tended to drop from 6.0% at baseline (14/232) to
      1.5% at 3 months (12/137) (P = .109), with no significant between-group
      differences in the rate of metabolic syndrome at baseline or at completion of the
      intervention. CONCLUSIONS: An intervention programme that focuses on both parents
      and children was found to have positive short-term and long-term effects on BMI
      SDS.

PMID- 29345114
TI  - Introduction to the special issue on myelin plasticity in the central nervous
      system.

PMID- 29345115
TI  - Metatranscriptome analysis reveals environmental and diel regulation of a
      Heterosigma akashiwo (raphidophyceae) bloom.
AB  - Despite numerous laboratory studies on physiologies of harmful algal bloom (HAB)
      species, physiologies of these algae during a natural bloom are understudied.
      Here, we investigated a bloom of the raphidophyte Heterosigma akashiwo in the
      East China Sea in 2014 using metabarcode (18S rDNA) and metatranscriptome
      sequencing. Based on 18S rDNA analyses, the phytoplankton community shifted from
      high diversity in the pre-bloom stage to H. akashiwo predominance during the
      bloom. A sharp decrease in ambient dissolved inorganic phosphate and strong up
      regulation of phosphate and dissolved organic phosphorus (DOP) uptake genes,
      including the rarely documented (ppGpp)ase, in H. akashiwo from pre-bloom to
      bloom was indicative of rapid phosphorus uptake and efficient utilization of DOP
      that might be a driver of the H. akashiwo bloom. Furthermore, observed up
      regulated expression of mixotrophy-related genes suggests potential contribution
      of mixotrophy to the bloom. Accelerating photosynthetic carbon fixation was also
      implied by the up-regulation of carbonic anhydrase genes during the bloom.
      Notably, we also observed a strong morning-to-afternoon shift in the expression
      of many genes. Our findings provide insights into metabolic processes likely
      important for H. akashiwo bloom formation, and suggest the need to consider
      timing of sampling in field studies on this alga.

PMID- 29345116
TI  - Notch1 gain of function in skeletal muscles leads to neuromuscular junction
      formation defects and neonatal death.

PMID- 29345119
TI  - Beyond the headlines - JEADV editor's pick of the year 2017.

PMID- 29345120
TI  - Fragrance contact allergy.

PMID- 29345117
TI  - Candida auris: A systematic review and meta-analysis of current updates on an
      emerging multidrug-resistant pathogen.
AB  - From 2009, Candida auris has emerged as a multidrug-resistant ascomycete yeast
      pathogen with the capacity for easy transmission between patients and hospitals,
      as well as persistence on environmental surfaces. Its association with high
      mortalities, breakthrough and persistent candidaemia, inconsistencies in
      susceptibility testing results, misidentification by available commercial
      identification systems and treatment failure, complicates its management and
      detection. Within the last nine years, C. auris has been increasingly reported
      from far-Eastern Asia, the Middle East, Africa, Europe, South and North America
      with substantial fatalities and misidentification. Herein, I provide a systematic
      and thorough review of this emerging pathogen. Meta-analysis showed that at least
      742 C. auris isolates have been reported in 16 countries, with most of these
      being from India (>=243), USA (>=232) and UK (>=103) (p-value = .0355) within
      2013-2017. Most isolates were from males (64.76%) (p-value = .0329) and blood
      (67.48%) (p-value < .0001), with substantial crude mortality (29.75%) (p-value =
      .0488). Affected patients presented with other comorbidities: diabetes (>=52),
      sepsis (>=48), lung diseases (>=39), kidney diseases (>=32) etc. (p-value <
      .0001). Resistance to fluconazole (44.29%), amphotericin B (15.46%), voriconazole
      (12.67%), caspofungin (3.48%) etc. were common (p-value = .0059). Commonly used
      diagnostic tools included PCR (30.38%), Bruker MALDI-TOF MS (14.00%), Vitek 2 YST
      ID (11.93%), AFLP (11.55%) and WGS (10.04%) (p-value = .002). Multidrug
      resistance, high attributable mortality and persistence are associated with C.
      auris infections. Two novel drugs, SCY-078 and VT-1598, are currently in the
      pipeline. Contact precautions, strict infection control, periodic surveillance
      and cleaning with chlorine-based detergents, efficient, faster and cheaper
      detection tools are necessary for prevention, containment and early diagnosis of
      C. auris infections.

PMID- 29345122
TI  - Ten years of Journal of Biophotonics.

PMID- 29345121
TI  - Suspected hypersensitivity to cervicovaginal fluid - what can we learn from the
      seminal plasma allergy story?

PMID- 29345123
TI  - The effects of lifestyle changes on serum lipid levels in children in a real life
      setting.
AB  - OBJECTIVE: Studies have shown improvement in lipid levels after institution of
      lifestyle changes in children enrolled in closely monitored programs. There
      programs are difficult to mimic in real world clinics. We aim to determine if
      diet and exercise result in improvement in lipid levels in patients seen in a
      designated lipid clinic in a real life setting. DESIGN: Retrospective review of
      patients followed for dyslipidemia at the Texas Children's Hospital Lipid Clinic
      from May 1, 2012 to May 1, 2015. Patients included were seen more than once, had
      repeat lipid testing, and abnormal baseline lipid levels. Multivariate analysis
      using mixed models were performed to compare outcomes in patients who did and did
      not participate in lifestyle change. RESULTS: Of the 268 patients seen within the
      study period, 174 (56% male, 44% female) met inclusion criteria. Median age was
      11 years. Compared to patients who did not make lifestyle changes: patients who
      made only diet changes demonstrated significant improvement in weight only (slope
      = -1.55, P-value = .014), and those who made only exercise changes demonstrated
      significant improvements in serum cholesterol (slope = -22.8, P-value = .017) and
      non-HDL cholesterol (slope = -28.7, P-value = < .01) levels. Patients who
      participated in both diet and exercise demonstrated significant improvement in
      weight (slope = -1.13, P-value = .011), diastolic blood pressure (slope = -1.82,
      P-value = < .01), and serum lipid levels: LDL (slope = -10.8, P-value = 0.017),
      HDL (slope = 1.52, P-value = .24), Triglycerides (slope = -0.11, P-value = .033)
      compared to those who did not make lifestyle changes. CONCLUSIONS: Outpatient
      management of dyslipidemia is difficult. Only patients who participated in both
      diet and exercise showed significant improvement in outcomes when compared to
      those who did not make lifestyle changes.

PMID- 29345124
TI  - Disposable Morpho menelaus Based Flexible Microfluidic and Electronic Sensor for
      the Diagnosis of Neurodegenerative Disease.
AB  - Rapid early disease prevention or precise diagnosis is almost impossible in low
      resource settings. Natural ordered structures in nature have great potential for
      the development of ultrasensitive biosensors. Here, motivated by the unique
      structures and extraordinary functionalities of ordered structures in nature, a
      biosensor based on butterfly wings is presented. In this study, a flexible Morpho
      menelaus (M. menelaus) based wearable sensor is integrated with a microfluidic
      system and electronic networks to facilitate the diagnosis of neurodegenerative
      disease (ND). In the microfluidic section, the structural characteristics of the
      M. menelaus wings up layer are combined with SiO2 nanoparticles to form a
      heterostructure. The fluorescent enhancement property of the heterostructure is
      used to increase the fluorescent intensity for multiplex detection of two
      proteins: IgG and AD7c-NTP. For the electronic section, conductive ink is blade
      coated on the under layer of wings for measuring resistance change rate to obtain
      the frequency of static tremors of ND patients. The disposable M. menelaus based
      flexible microfluidic and electronic sensor enables biochemical-physiological
      hybrid monitoring of ND. The sensor is also amenable to a variety of
      applications, such as comprehensive personal healthcare and human-machine
      interaction.

PMID- 29345125
TI  - Naturally acquired bovine besnoitiosis: Disease frequency, risk and outcome in an
      endemically infected beef herd.
AB  - The recent spread of bovine besnoitiosis warrants further epidemiological
      investigations to improve the knowledge on disease development. Thus, a 4-year
      longitudinal open cohort study was conducted in the first German cattle herd
      naturally infected with Besnoitia besnoiti. At seven herd-visits between 2008 and
      2012, fourteen breeding bulls (>1.5 years) and 131 females (>1 year) were
      examined clinically and serologically. In females, clinical and serological
      prevalences, incidence and remission rates were determined. In addition, the
      association of age, antibody levels and number of visible parasitic cysts with
      clinical and serological outcome was investigated. The seroprevalence (89.4%
      100%) and serological incidence rate (140.5 per 100 animal-years) were
      considerably higher than the clinical prevalence (23.5%-36.6%) and clinical
      incidence rate (16.7 per 100 animal-years). Of 33 new clinical and 12 new
      serological cases, only 6.7% (3/45) attracted attention with clinical signs of
      acute bovine besnoitiosis. The apparent serological remission rate (1.9 per 100
      animal-years) was considerably lower than the clinical remission rate (37.3 per
      100 animal-years). A median cyst score of <1 and mean immunofluorescent antibody
      test (IFAT) titre of <=1,600 over the entire observation period was significantly
      associated with a negative clinical outcome at the end. Overall cyst score was
      not significantly associated with serological outcome and age had no significant
      influence on clinical and serological outcome. Within 4 years, there was a
      significant reduction in cyst scores and IFAT titres in the same animals, leading
      to eight clinically and serologically negative animals in the end. Two initially
      negative animals achieved clinical and apparent serological remission in about
      2.5 years. In bulls, the time between herd entry and seroconversion was 7-30
      months and the serological incidence rate was nearly identical to the rate in
      females (142.0 per 100 animal-years). This shows that a high B. besnoiti
      prevalence leads to infection of bulls within a short time period.

PMID- 29345126
TI  - Enantioselective Synthesis of Boryl Tetrahydroquinolines via Cu-Catalyzed
      Hydroboration.
AB  - A Cu-catalyzed regio- and enantioselective hydroboration of 1,2-dihydroquinolines
      with high yields and excellent enantioselectivities (up to 98% ee) was presented.
      This method could be applied in the asymmetric synthesis of the important
      intermediates used in the enantioselective synthesis of the potential agent
      Sumanirole for the treatment of Parkinson's disease and of the potentially
      interesting positive inotropic agent (S)-903.

PMID- 29345127
TI  - Monochlorinated to Octachlorinated Polychlorinated Dibenzo-p-dioxin and
      Dibenzofuran Emissions in Sintering Fly Ash from Multiple-Field Electrostatic
      Precipitators.
AB  - Polychlorinated dibenzo-p-dioxin and dibenzofuran (PCDD/F) emissions in fly ash
      from multiple-field electrostatic precipitators in different sized sintering
      plants were studied. The monochlorinated-trichlorinated and tetrachlorinated
      octachlorinated PCDD/F concentrations were higher for small plants (90 m2) than
      for medium (91-180 m2) and large (>180 m2) plants. The PCDD/F concentrations and
      less-chlorinated PCDD/F contributions to the total PCDD/F concentrations
      increased as the fly ash particle size decreased moving through the precipitator
      stages; the abundance of monochlorinated-trichlorinated PCDD/F congeners and
      homologues also increased. The ash particle size and surface area can be directly
      used to indicate monochlorinated-trichlorinated PCDD/Fs and toxic equivalents
      (TEQs). Previously ignored PCDD/F emissions in discarded fly ash were identified.
      Estimated total monochlorinated-trichlorinated PCDD/F and TEQ emissions in
      discarded fly ash were 155 and 1.979 kg TEQ, respectively, in 2003-2014, and the
      ratio between annual PCDD/F emissions in discarded fly ash and flue gases has
      gradually increased. Reductions in monochlorinated-trichlorinated PCDD/F emitted
      in flue gas and fly ash in 2003-2014 were 28 and 40 kg, respectively, because of
      the phasing out of small-scale plants. Reductions in TEQs emitted in flue gas and
      fly ash in 2003-2014 were 7476 and 180 g TEQ, respectively.

PMID- 29345128
TI  - Synthesis of alpha-Formylated N-Heterocycles and Their 1,1-Diacetates from
      Inactivated Cyclic Amines Involving an Oxidative Ring Contraction.
AB  - A novel synthesis of pyrrolidine-2-carbaldehydes or tetrahydropyridine-2
      carbaldehydes from the cascade reactions of N-arylpiperidines or N-arylazepanes
      is presented. Mechanistically, the formation of the title compounds involves an
      unprecedented oxidative ring contraction of inactivated cyclic amines via
      Cu(OAc)2/KI/O2-promoted oxidative cleavage and reformation of the C-N bond.
      Interestingly, when PhI(OAc)2 was used in place of KI, 1,1-diacetates of the
      corresponding aldehydes were directly obtained with good efficiency. To the best
      of our knowledge, this is the first example of regioselective C(sp3)-H bond
      functionalization and C(sp3)-N bond activation of saturated cyclic amines using
      copper salt and oxygen.

PMID- 29345129
TI  - Displacement of Dinitrogen by Oxygen: A Methodology for the Catalytic Conversion
      of Diazocarbonyl Compounds to Ketocarbonyl Compounds by 2,6-Dichloropyridine-N
      oxide.
AB  - Dirhodium(II) catalyzed dinitrogen extrusion from diazocarbonyl compounds by 2,6
      dichloropyridine-N-oxide forms ketocarbonyl compounds in near-quantitative
      yields. Reactions occur at room temperature, and the pyridine product does not
      coordinate with dirhodium(II) to inhibit catalysis. Anhydrous tricarbonyl
      compounds, as well as dicarbonyl compounds, are conveniently prepared by this
      methodology, and they have been used in situ for catalytic ene and aldol
      transformations.

PMID- 29345130
TI  - Two Marine Cyanobacterial Aplysiatoxin Polyketides, Neo-debromoaplysiatoxin A and
      B, with K+ Channel Inhibition Activity.
AB  - The isolation and structure elucidation of two cyanobacterial debromoaplysiatoxin
      (DAT) analogues, neo-debromoaplysiatoxin A (1) and neo-debromoaplysiatoxin B (2),
      were reported and found to possess 6/10/6 and 6/6/6 fused-ring systems,
      respectively, which are rarely seen among aplysiatoxins. Both compounds exhibited
      potent blocking activity against Kv1.5 with IC50 values of 6.94 +/- 0.26 and 0.30
      +/- 0.05 MUM, respectively. These findings suggest the potential of aplysiatoxin
      analogues in modulating ionic channels and also provide links between the DAT
      target, protein kinase C, and cell regulation.

PMID- 29345131
TI  - Photolithography-Based Nanopatterning Using Re-entrant Photoresist Profile.
AB  - Photolithography based on optical mask is widely used in academic research
      laboratories due to its low cost, simple mechanism, and ability to pattern in
      micron-sized features on a wafer-scale area. Because the resolution is bound by
      diffraction limits of the light source, nanoscale patterning using
      photolithography requires short-wavelength light source combined with
      sophisticated optical elements, adding complexity and cost. In this paper, a
      novel method of subwavelength patterning process using conventional i-line
      mercury lamp is introduced, without the use of such advanced optical tools. The
      method utilizes the re-entrant geometry of image reversal photoresist produced
      from the developing process, where a secondary mask is generated by isotropically
      depositing a metal layer to cover the re-entrant profile of the photoresist.
      Removing the photoresist by applying ultrasonic vibrations in acetone bath
      uniformly cracks the metal layer at the sidewalls of the re-entrant profile,
      exposing the substrate with a reduced feature size. The width of the initial mask
      pattern can be reduced by 400 nm in a controlled manner, regardless of the
      original width choice. As a result, the method is shown to achieve sub-100 nm
      scale linear patterns compatible for both subsequent deposition process and dry
      etching process. Our approach is applicable to various shapes of the patterns and
      can be used in electronic device fabrication requiring nanoscale lithography
      patterning, such as the gate fabrication of AlGaN/GaN high-electron-mobility
      transistor.

PMID- 29345132
TI  - Rh(III)-Catalyzed Acceptorless Dehydrogenative Coupling of (Hetero)arenes with 2
      Carboxyl Allylic Alcohols.
AB  - Rhodium(III)-catalyzed C-H activation of (hetero)arenes and redox-neutral
      coupling with 2-carboxyl allylic alcohols has been realized for the construction
      of beta-aryl ketones. This reaction occurred efficiently at a relatively low
      catalyst loading via initial dehydrogenative alkylation to give a beta-keto
      carboxylic acid, followed by decarboxylation.

PMID- 29345133
TI  - Stable Organic Radicals as Hole Injection Dopants for Efficient Optoelectronics.
AB  - Precursors of reactive organic radicals have been widely used as n-dopants in
      electron-transporting materials to improve electron conductivity and enhance
      electron injection. However, the utilization of organic radicals in hole
      counterparts has been ignored. In this work, stable organic radicals have been
      proved for the first time to be efficient dopants to enhance hole injection. From
      the absorbance spectra and the ultraviolet photoelectron spectra, we could
      observe an efficient electron transfer between the organic radical, (4-N
      carbazolyl-2,6-dichlorophenyl)bis(2,4,6-trichlorophenyl)methyl (TTM-1Cz), and the
      widely used hole injection material, 1,4,5,8,9,11-hexaazatriphenylene
      hexacarbonitrile (HAT-CN). When the unpaired electron of TTM-1Cz is transferred
      to HAT-CN, it would be oxidized to a TTM-1Cz cation with a newly formed lowest
      unoccupied molecular orbital which is quite close to the highest occupied
      molecular orbital (HOMO) of the hole-transporting material (HTM). In this way,
      the TTM-1Cz cation would promote the electron extraction from the HOMO of the HTM
      and improve hole injection. Using TTM-1Cz-doped HAT-CN as the hole injection
      layer, efficient organic light-emitting diodes with extremely low voltages can be
      attained.

PMID- 29345134
TI  - Nanoscale Imaging of Primary Cilia with Scanning Ion Conductance Microscopy.
AB  - Primary cilia are hair-like sensory organelles whose dimensions and location vary
      with cell type and culture condition. Herein, we employed scanning ion
      conductance microscopy (SICM) to visualize the topography of primary cilia from
      different cell types. By combining SICM with fluorescence imaging, we
      successfully distinguished between surface cilia that project outward from the
      cell surface and subsurface cilia that are trapped below it. The nanoscale
      structure of the ciliary pocket, which cannot be easily identified using a
      confocal fluorescence microscope, was observed in SICM images. Furthermore, we
      developed a topographic reconstruction method using current-distance profiles to
      evaluate the relationship between set point and topographic image and found that
      a low set point is important for detecting the true topography of a primary
      cilium using hopping mode SICM.

PMID- 29345135
TI  - The Deposition and Elimination of Glucosinolate Metabolites Derived from Rapeseed
      Meal in Eggs of Laying Hens.
AB  - This study was to investigate the deposition and elimination of glucosinolate
      metabolites including 5-vinyl-1,3-oxazolidine-2-thione (5-VOT) and thiocyanate
      ion (SCN-) derived from rapeseed meal (RSM) in hen eggs. During 12 weeks
      accumulation phase, the serum triiodothyronine, thyronine, blood urea nitrogen,
      kidney index, and thyroid index linearly increased with the RSM at week 12 (P <
      0.05). The thyroid histopathology revealed a sign of hyperplastic goiter in hens
      fed with 17.64-29.40% RSM. The 5-VOT content of eggs (Y, ng/g) was correlated
      with 5-VOT intake (X2, MUg/d.bird) and 5-VOT feeding time (X1, week): Y = 54.94X1
      + 0.51X2 - 430.34 (P < 0.01, R2 = 0.80). The SCN- content of eggs (Y, mg/kg) was
      correlated with RSM intake (X2, MUg/d.bird) and RSM feeding time (X1, week): Y =
      0.095X1 + 0.302X2 - 0.4211 (P < 0.01, R2 = 0.70). After a 4-week withdrawal of
      RSM, the 5-VOT and SCN- did not show in eggs. Taken together, 5.88% RSM with
      dietary supplements of 23.55 mg/kg 5-VOT and 10.76 mg/kg SCN- had no effects on
      hens with regard to serum parameters, organ index, and thyroid histopathology,
      and more than 4 weeks withdrawal should be considered for human and hen health.

PMID- 29345136
TI  - Regioselective Reaction of Heterocyclic N-Oxides, an Acyl Chloride, and Cyclic
      Thioethers.
AB  - Treatment of electron deficient pyridine N-oxides with 4-nitrobenzoyl chloride
      and a cyclic thioether in the presence of triethylamine leads to the
      corresponding 2-functionalized product in up to a 74% isolated yield. The
      transformation can also be accomplished with alternative nitrogen containing
      heterocycles, including quinolines, pyrimidines, and pyrazines. To expand the
      scope of the transformation, diisopropyl ether can be used as the reaction medium
      to allow for the use of solid thioether substrates.

PMID- 29345137
TI  - Formal Insertion of Thioketenes into Donor-Acceptor Cyclopropanes by Lewis Acid
      Catalysis.
AB  - Donor-acceptor cyclopropanes were reacted under Lewis acid catalysis with 3
      thioxocyclobutanones as surrogates for disubstituted thioketenes. A broad scope
      of 2-substituted tetrahydrothiophenes with a semicyclic double bond was obtained
      under mild conditions with high functional group tolerance and in excellent
      yield. A sequence of a formal [3 + 2]-cycloaddition followed by the subsequent
      release of disubstituted ketene is postulated as the mechanism.

PMID- 29345138
TI  - A Four-Step Synthesis of (+/-)-gamma-Lycorane via Pd0-Catalyzed Double C(sp2)
      H/C(sp3)-H Arylation.
AB  - An expedient synthesis of lycorine alkaloids is reported using a palladium(0)
      catalyzed double C-X/C-H arylation as the key step. The selectivity of this
      reaction was controlled through the judicious choice of the two halogen atoms,
      and its generality was demonstrated through the construction of various
      substituted pyrrolophenanthridinones. A selective arene hydrogenation allowed for
      the completion of the synthesis of (+/-)-gamma-lycorane in just four steps from
      commercially available precursors.

PMID- 29345139
TI  - Catalytically Enantioselective Synthesis of Acyclic alpha-Tertiary Amines through
      Desymmetrization of 2-Substituted 2-Nitro-1,3-diols.
AB  - Highly enantioselective synthesis of acyclic alpha-tertiary amines through
      asymmetric desymmetrization is reported. This approach is based on chiral
      phosphoric acid mediated, enantioselective, oxidative desymmetrization of 2
      substituted 2-nitro-1,3-diolbenzylidine acetals in the presence of DMDO as an
      oxidant. The method allows for the formation of a wide variety of chiral 2-nitro
      1,3-diols in high enantioselectivity, which could be transformed into optically
      pure, unnatural alpha-alkyl series. The synthetic utility of this method has been
      further demonstrated by the expedient construction of the core structure of
      natural products manzacidins enantioselectively.

PMID- 29345140
TI  - High-Efficiency and Stable Organic Solar Cells Enabled by Dual Cathode Buffer
      Layers.
AB  - Various cathode interface materials have been used in organic solar cells (OSCs)
      to realize high performance. However, most cathode interface materials have their
      respective weaknesses in maximizing the efficiency or stability of OSCs. Herein,
      three kinds of alcohol-soluble cathode interfacial materials are combined with
      bathocuproine (BCP) to serve as multifunctional bilayer cathode buffers for the
      regular OSCs, and thus greatly enhanced power conversion efficiencies over 10.11%
      and significantly improved device stability have been achieved. By utilizing
      double interlayers, both light absorption and light distribution in active layer
      are improved. Furthermore, double interlayers offer favorable energy-level
      alignment, alcohol treatment, and duplicate protection of active layer, resulting
      in significantly reduced leakage current, suppressed recombination, and efficient
      charge collection. The improved device stability is related to the blocking
      effect of the complex formed between BCP and the metal electrode and the
      additional protection effect of the underlying alcohol-soluble materials. In view
      of the universal use of alcohol-soluble organic electrolyte as cathode buffer
      layers and by courtesy of the superiority of the double cathode layers relative
      to the monolayer controls, the double interlayer strategy demonstrated here opens
      a new way to fully exploiting the potential of OSCs and is believed to be
      extended to a wider application.

PMID- 29345142
TI  - Mediating Role of Career Coaching on Job-Search Behavior of Older Generations.
AB  - This study focuses on career development processes and options for older workers
      in South Korea and explores how career coaching enhances their career development
      efforts and transition needs. The purpose of this study is to investigate the
      structural relationship between older employees' goal-setting, self-efficacy, and
      job-search behavior mediated by career coaching. A total of 249 participants were
      recruited in a metropolitan city in South Korea. Based on the literature review,
      hypotheses were developed and tested on the structural model and the following
      findings were revealed. First, the findings indicate a positive effect of self
      efficacy on older workers' job-search behavior. Second, the value of career
      coaching was found to affect older workers' job-search behavior in the South
      Korean context. Third, career-goal commitment alone did not have a positive
      significant effect on job-search behavior, but it was influential through the
      mediating process of the perceived quality of the career coaching program
      provided by an employment center in South Korea.

PMID- 29345141
TI  - Creating Hierarchical Pores by Controlled Linker Thermolysis in Multivariate
      Metal-Organic Frameworks.
AB  - Sufficient pore size, appropriate stability, and hierarchical porosity are three
      prerequisites for open frameworks designed for drug delivery, enzyme
      immobilization, and catalysis involving large molecules. Herein, we report a
      powerful and general strategy, linker thermolysis, to construct ultrastable
      hierarchically porous metal-organic frameworks (HP-MOFs) with tunable pore size
      distribution. Linker instability, usually an undesirable trait of MOFs, was
      exploited to create mesopores by generating crystal defects throughout a
      microporous MOF crystal via thermolysis. The crystallinity and stability of HP
      MOFs remain after thermolabile linkers are selectively removed from multivariate
      metal-organic frameworks (MTV-MOFs) through a decarboxylation process. A domain
      based linker spatial distribution was found to be critical for creating
      hierarchical pores inside MTV-MOFs. Furthermore, linker thermolysis promotes the
      formation of ultrasmall metal oxide nanoparticles immobilized in an open
      framework that exhibits high catalytic activity for Lewis acid-catalyzed
      reactions. Most importantly, this work provides fresh insights into the
      connection between linker apportionment and vacancy distribution, which may shed
      light on probing the disordered linker apportionment in multivariate systems, a
      long-standing challenge in the study of MTV-MOFs.

PMID- 29345143
TI  - Readability of Online Health Information: A Meta-Narrative Systematic Review.
AB  - Online health information should meet the reading level for the general public
      (set at sixth-grade level). Readability is a key requirement for information to
      be helpful and improve quality of care. The authors conducted a systematic review
      to evaluate the readability of online health information in the United States and
      Canada. Out of 3743 references, the authors included 157 cross-sectional studies
      evaluating 7891 websites using 13 readability scales. The mean readability grade
      level across websites ranged from grade 10 to 15 based on the different scales.
      Stratification by specialty, health condition, and type of organization producing
      information revealed the same findings. In conclusion, online health information
      in the United States and Canada has a readability level that is inappropriate for
      general public use. Poor readability can lead to misinformation and may have a
      detrimental effect on health. Efforts are needed to improve readability and the
      content of online health information.

PMID- 29345144
TI  - Pilot Randomized Controlled Trial of the GO Game Intervention on Cognitive
      Function.
AB  - This study investigated the effects of an intervention using the game "GO" on
      cognitive function in nursing home residents and evaluated the acquisition of GO
      according to each stage of dementia. Participants were randomly assigned to
      either the GO intervention group or a control group, and the intervention was
      performed once weekly for 15 weeks. Cognitive tests were conducted before and
      after intervention, and 17 participants were included in the final analysis.
      Analysis of covariance demonstrated that in the intervention group, the digit
      span total score significantly improved and the digit span backward score was
      maintained, whereas these scores decreased in the control group. All
      participants, including those who had moderate dementia, acquired the rules of
      the game, and participants with mild cognitive impairment and mild dementia could
      play the game successfully. This study indicates that GO might improve the
      cognitive function of residents living in nursing homes.

PMID- 29345145
TI  - Process improvement methodologies uncover unexpected gaps in stroke care.
AB  - Background The diagnosis and treatment of acute stroke requires timed and
      coordinated effort across multiple clinical teams. Purpose To analyze the
      frequency and temporal distribution of emergent stroke evaluations (ESEs) to
      identify potential contributory workflow factors that may delay the initiation
      and subsequent evaluation of emergency department stroke patients. Material and
      Methods A total of 719 sentinel ESEs with concurrent neuroimaging were identified
      over a 22-month retrospective time period. Frequency data were tabulated and odds
      ratios calculated. Results Of all ESEs, 5% occur between 01:00 and 07:00. ESEs
      were most frequent during the late morning and early afternoon hours (10:00
      14:00). Unexpectedly, there was a statistically significant decline in the
      frequency of ESEs that occur at the 14:00 time point. Conclusion Temporal
      analysis of ESEs in the emergency department allowed us to identify an unexpected
      decrease in ESEs and through process improvement methodologies (Lean and Six
      Sigma) and identify potential workflow elements contributing to this observation.

PMID- 29345146
TI  - Quantitative contrast-enhanced ultrasound for monitoring vedolizumab therapy in
      inflammatory bowel disease patients: a pilot study.
AB  - Background Microvascularization of the bowel wall can be visualized and
      quantified non-invasively by software-assisted analysis of derived time-intensity
      curves. Purpose To perform software-based quantification of bowel wall perfusion
      using quantitative contrast-enhanced ultrasound (CEUS) according to clinical
      response in patients with inflammatory bowel disease treated with vedolizumab.
      Material and Methods In a prospective study, in 18 out of 34 patients, high
      frequency ultrasound of bowel wall thickness using color Doppler flow combined
      with CEUS was performed at baseline and after 14 weeks of treatment with
      vedolizumab. Clinical activity scores at week 14 were used to differentiate
      between responders and non-responders. CEUS parameters were calculated by
      software analysis of the video loops. Results Nine of 18 patients (11 with
      Crohn's disease and seven with ulcerative colitis) showed response to treatment
      with vedolizumab. Overall, the responder group showed a significant decrease in
      the semi-quantitative color Doppler vascularization score. Amplitude-derived CEUS
      parameters of mural microvascularization such as peak enhancement or wash-in rate
      decreased in responders, in contrast with non-responders. Time-derived parameters
      remained stable or increased during treatment in all patients. Conclusion
      Analysis of bowel microvascularization by CEUS shows statistically significant
      changes in the wash-in-rate related to response of vedolizumab therapy.

PMID- 29345148
TI  - ERRATUM.

PMID- 29345147
TI  - The Complexities of Family Caregiving at Work: A Mixed-Methods Study.
AB  - The current project examined the impact of caregiving and caregiving-work
      conflict on employees' well-being. A sequential explanatory mixed-methods design
      (QUAN->qual) was utilized, and a total of 880 employees from a large health-care
      plan employer completed an online survey. Forty-five caregivers who completed the
      survey also participated in one of the five focus groups held 1 to 2 months
      later. Employed caregivers were significantly ( p < .05) more likely to indicate
      poorer physical and mental health than noncaregivers; among caregivers ( n =
      370), caregiving-work conflict emerged as the most significant predictor of well
      being and fully mediated the empirical relationship between burden and well
      being. The focus group findings complemented the quantitative results; many of
      the challenges employed caregivers experience stem from their ability or
      inability to effectively balance their employment and caregiving roles. The
      results suggest the need to focus on caregiving-work conflict when constructing
      new or translating existing evidence-based caregiver interventions.

PMID- 29345149
TI  - Medical management of brain metastases and leptomeningeal disease in patients
      with breast carcinoma.
AB  - Breast cancer is the most common malignancy among women and accounts for the
      second highest number of cancer-related deaths. With patients surviving longer
      due to advances in systemic control, the incidence of CNS involvement is
      increasing; however, the management of CNS metastases has not undergone parallel
      advancements. The blood-brain barrier limits the efficacy of most systemic
      chemotherapies, and the utilization of surgery and radiation beyond first-line
      therapy is limited. We will explore the recent developments in the medical
      management of breast cancer brain metastasis. Beyond traditional chemotherapy, we
      will also discuss targeted therapies and immunotherapies which may provide a
      survival benefit to this population and thus, offer further treatment options and
      a path for future research and treatment advances.

PMID- 29345150
TI  - An Initial Assessment of the Utility of Validated Alcohol and Drug Screening
      Tools in Predicting 30-Day Readmission to Adult General Medicine Wards.
AB  - Previous studies have identified drug and alcohol use as risk factors for
      readmission using claims data, but not by using substance use screening scores.
      This preliminary study tested the hypothesis that prevalence of 30-day
      readmission would be higher among patients screening positive on the 10-item
      Alcohol Use Disorders Identification Test (AUDIT-10) or the 10-item Drug Abuse
      Screening Test (DAST-10) tools at intake than among the general patient
      population. Social workers screened 4708 adult inpatients using prescreening
      questions followed by the AUDIT-10 and/or DAST-10. Patients with positive screens
      were followed for readmissions within 30 days of discharge. A positive screening
      score on the AUDIT-10 or DAST-10 instrument at intake was associated with higher
      risk of readmission to the general medicine wards within 30 days; this
      relationship appears complex and subject to mediation. Post hoc chart review
      found that the majority of readmissions among patients with positive screens were
      not immediately attributable to substance use. Further study is needed to verify
      these preliminary findings.

PMID- 29345151
TI  - Emerging technologies for biotherapeutic bioanalysis from a high-throughput and
      multiplexing perspective: insights from an AAPS emerging technology action
      program committee.
AB  - This manuscript aims to provide insights and updates on emerging technologies
      from a throughput and multiplexing perspective and to update readers on changes
      in previously reported technologies. The technologies discussed range from
      nascent (ultrasensitive Cira, Intellicyt(r), Dynaxi and CaptsureTM) to the more
      established (Ella and SQIDliteTM). For the nascent technologies, there was an
      emphasis on user interviews and reviews, where available, to help provide an
      unbiased view to our readers. For the Ella, a review of published user data as
      well as author and other user experiences are summarized. Due to their emergent
      nature, all the technologies described are applicable in the early drug
      development stage, may require an upfront investment of capital and may not
      perform as expected.

PMID- 29345152
TI  - Changes in radiotherapy fractionation-breast cancer.
AB  - Conventional fractionation for half a century has been justified on the basis
      that 2.0 Gy fractions spare dose-limiting late-responding normal tissues to a
      greater degree than cancerous tissues. Early indications that breast cancer
      responds more strongly to fraction size than many other common cancers were
      followed several decades of investigation, but there is now reliable Level I
      evidence that this is the case. Four randomised trials testing fraction sizes in
      the range 2.7-3.3 Gy have reported 10-year follow up in almost 8000 patients, and
      they provide robust estimates of alpha/beta in the range of 3 Gy. The implication
      is that there are no advantages in terms of safety or effectiveness of persisting
      with 2.0 Gy fractions in patients with breast cancer. 15- or 16-fraction
      schedules are replacing the conventional 25-fraction regimen as a standard of
      care for adjuvant therapy in an increasing number of countries. A number of
      concerns relating to the appropriateness of hypofractionation in patient
      subgroups, including those treated post-mastectomy, advanced local-regional
      disease and/or to lymphatic pathways are addressed. Meanwhile, hypofractionation
      can be exploited to modulate dose intensity across the breast according to
      relapse risk by varying fraction size across the treatment volume. The lower
      limits of hypofractionation are currently being explored, one approach testing a
      5-fraction schedule of local-regional radiotherapy delivered in 1 week.

PMID- 29345153
TI  - Selective serotonin reuptake inhibitor use in pregnant women; pharmacogenetics,
      drug-drug interactions and adverse effects.
AB  - INTRODUCTION: Possible negative effects of selective serotonin reuptake
      inhibitors (SSRIs) in pregnancy relate to congenital anomalies, negative
      perinatal events and neurodevelopmental outcome. Many studies are confounded by
      the underlying maternal disease and by pharmacogenetic and pharmacokinetic
      differences of these drugs. Areas covered: The possible interactions of SSRIs and
      serotonin and norepinephrine reuptake inhibitors with other drugs and the known
      effects of SSRIs on congenital anomalies, perinatal and neurodevelopmental
      outcome. Expert opinion: SSRIs should be given with caution when combined with
      other drugs that are metabolized by cytochrome P450 enzymes. SSRIs apparently
      increase the rate of severe cardiac malformations, induce neonatal adaptation
      problems in up to 30% of the offspring, increase the rate of persistent pulmonary
      hypertension of the newborn and possibly slightly increase the rate of
      prematurity and low birth weight. Most neurodevelopmental follow up studies did
      not find significant cognitive impairments except some transient gross motor
      delay, slight impairment of language abilities and possibly behavioral changes.
      The literature on the possible association of SSRIs with autism spectrum disorder
      is inconsistent; if an association exists, it is apparently throughout pregnancy.
      The risk associated with treatment discontinuation seems to outweigh the risk of
      treatment, as severe maternal depression may negatively affect the child's
      development. If needed, treatment should continue in pregnancy with the minimal
      effective dose.

PMID- 29345154
TI  - Trends and repetition of non-fatal suicidal behaviour: analyses of the Gold Coast
      University Hospital's Emergency Department.
AB  - : Objective The aim of the current paper is to analyse time trends of non-fatal
      suicidal behaviour (NFSB) and its repetition at the Gold Coast in 2005-2015.
      Methods Data on presentations for NFSB were obtained from the Emergency
      Department (ED) Information System. Potential cases were identified through
      keyword searches, which were further scrutinised and coded. Annual person-based
      age-standardised rates for NFSB were calculated. Chi-square test, Poisson
      regression and Cox proportional hazards regression were used. RESULTS: There was
      a significant increase in the age-standardised rates of NFSB for males (incidence
      Rate Ratio = 1.05; 95% confidence interval (CI): 1.04-1.07) and females (iRR =
      1.06; 95% CI: 1.04-1.07). Age-specific rates showed significant increases for all
      age groups, except 25-34 and 55+ for females. Different types of poisoning were
      the predominant method of NFSB (poisoning only - 61.7% of episodes), followed by
      cutting (23%). Within the first year after the index episode, 13.4% of subjects
      repeated NFSB. Multivariate Cox regression model showed that sex, age and method
      predicted repetition. CONCLUSION: The increasing trends of NFSB and relatively
      high repetition rates emphasise the need for preventative actions. Monitoring of
      NFSB at the ED level should be further extended in Australia.

PMID- 29345155
TI  - Minimally invasive adrenal surgery: virtue or vice?
AB  - Adrenocortical carcinoma (ACC) is a rare malignancy associated with poor
      prognosis despite available treatments. In patients with localized or locally
      advanced disease, complete resection with negative margins offers the only
      potential for cure. Unfortunately, most patients develop local and distant
      recurrence following initial resection highlighting the importance of meticulous
      surgical technique in the hands of an experienced surgeon. While minimally
      invasive surgery (MIS) has supplanted open surgery for small to medium-sized
      benign adrenal tumors, controversy surrounds the use of MIS for resection of ACC.
      We sought to provide an overview of the key oncological principles in the
      surgical management of ACC and to critically review the literature comparing
      outcomes between the open and MIS approaches.

PMID- 29345156
TI  - Pharmacokinetic drug evaluation of opicapone for the treatment of Parkinson's
      disease.
AB  - INTRODUCTION: Opicapone (OPC) is a novel, potent, reversible, and purely
      peripheral third-generation COMT inhibitor, which provides an enhancement in
      levodopa (L-Dopa) availability. It represents adjunctive therapy for L-Dopa
      treated patients with PD and motor fluctuations. Areas covered: The purpose of
      this study was to evaluate pharmacokinetic of OPC for the treatment of PD. Expert
      commentary: Oral OPC exhibits linear, dose-dependent absorption. However,
      following concomitant ingestion of a high-fat, high-calorie meal, the maximum
      plasma concentration will be decreased. A once-daily bedtime administration of
      OPC 1 h after the last daily L-Dopa/AADCi, are considered to avoid any
      interaction during the L-Dopa absorption phase. There are no clinically relevant
      effects of age (in adults), renal impairment or race on the pharmacokinetics of
      OPC. OPC dose adjustment is not needed in patients with mild to moderate chronic
      hepatic impairment. Opicapone exhibits the lowest potential for cytotoxicity in
      comparison with other COMT inhibitors. It significantly decreases COMT activity,
      with half-life of COMT inhibition in human erythrocytes of 61.6 h and increases
      systemic exposure to L-Dopa. This provides an enhancement in L-Dopa availability
      that translates into clinical benefit for PD patients in terms of significant
      decrease of OFF periods and increase in ON-time without troublesome dyskinesia.

PMID- 29345157
TI  - Evaluation of serum cysteine-rich protein 61 levels in patients with coronary
      artery disease.
AB  - AIM: The aim is to evaluate serum cysteine-rich protein 61 (Cyr61) levels in
      patients with coronary artery disease (CAD). PATIENTS & METHODS: Serum Cyr61
      levels were measured in 180 patients with CAD and 74 participants without CAD.
      RESULTS: Serum Cyr61 levels were significantly higher in CAD patients. Patients
      with acute coronary syndrome showed significantly higher Cyr61 than those with
      stable angina pectoris. Serum Cyr61 levels in complex lesion group were
      significantly higher. Serum Cyr61 was positively correlated with Gensini score
      and C-reactive protein. Multivariable logistic regression analyses demonstrated
      that serum Cyr61 levels were independently correlated with the existence of CAD
      (p = 0.01). CONCLUSION: Our study suggested Cyr61 as a potential biomarker in
      characterizing CAD and therapeutic target for CAD.

PMID- 29345158
TI  - The impact of probiotics and n-3 long-chain polyunsaturated fatty acids on
      intestinal permeability in pregnancy: a randomised clinical trial.
AB  - A disruption in intestinal barrier integrity may predispose individuals to
      metabolic aberrations, particularly during the vulnerable period of pregnancy. We
      investigated whether intestinal permeability, as measured by serum zonulin
      concentration, changes over the duration of pregnancy and whether this change is
      reflected in lipopolysaccharide (LPS) activity. Second, we tested in a randomised
      double-blind placebo controlled clinical trial the impact of consuming dietary
      probiotics and/or long chain polyunsaturated fatty acid (LC-PUFA) supplements in
      lowering serum zonulin concentration and LPS activity. The probiotic supplement
      was a combination of two bacteria, Bifidobacterium animalis ssp. lactis 420 and
      Lactobacillus rhamnosus HN001. This study included 200 overweight pregnant women
      participating in an on-going study; participants were randomised to consume
      either (1) probiotics, (2) LC-PUFA, (3) probiotics and LC-PUFA, or (4) placebo
      for each supplement. Blood samples were obtained at early, the baseline, and late
      pregnancy (mean 14 and 35 weeks of gestation, respectively). Serum zonulin
      concentration increased from early (mean (standard deviation): 62.7 (12.9) ng/ml)
      to late pregnancy by 5.3 (95%CI 3.7-6.9) ng/ml, and LPS activity increased from
      (0.16 (0.04) EU/ml) by 0.04 (95%CI 0.03-0.05) EU/ml. No differences among the
      intervention groups were detected in the change from early to late pregnancy in
      serum zonulin concentration (P=0.8) or LPS activity (P=0.2). The change in serum
      zonulin concentration during the pregnancy was associated with the weeks of
      follow up (r=0.25, P<0.001). Serum LPS activity was correlated with higher
      maternal weight gain (r=0.19, P=0.008). As a conclusion, intestinal permeability
      increased with the progression of pregnancy in overweight and obese women and was
      reflected in LPS activity. No efficacy of supplementation with probiotics and/or
      LC-PUFA was demonstrated in pregnancy-induced changes in serum zonulin
      concentration or LPS activity.

PMID- 29345159
TI  - Weighing in on the risks and benefits of probiotic use in HIV-infected and
      immunocompromised populations.
AB  - Probiotics are used in the prophylaxis and treatment of several conditions,
      including irritable bowel syndrome, diarrhoea, necrotising enterocolitis (NEC)
      and colic in infants. Despite the long history of probiotic use in humans, there
      is still significant debate about their efficacy and safety, particularly in HIV
      infected and immunocompromised individuals. Here, we reviewed the safety and
      adverse event (AE) reporting from clinical trials that have tested probiotics in
      at risk populations, including HIV-infected individuals, the terminally ill and
      elderly, and neonates. Our analysis suggests that the benefits of probiotic
      therapy outweigh their potential risks in HIV-infected populations, and in the
      treatment of colic and NEC in low birth weight or premature neonates. Most case
      reports of severe AEs were in the elderly and terminally ill, or in those with
      additional severe medical conditions. We conclude that probiotic use, as
      adjunctive treatment, is effective and safe in the majority of patients including
      HIV-infected individuals, although special care should be taken in individuals
      with extreme immunosuppression and severe medical conditions in all ages.

PMID- 29345160
TI  - Inherited forms of bladder cancer: a review of Lynch syndrome and other inherited
      conditions.
AB  - Environmental factors that play a role in the urothelial carcinogenesis have been
      well characterized. Current research is continuously exploring potential
      heritable forms of bladder cancer. Lynch syndrome is a well-known inheritable
      disease that increases the risk for a variety of cancers, including urothelial
      carcinomas. Screening of patients with known Lynch syndrome is important to
      evaluate for development of new primary tumors. Further study may provide more
      information on what level of follow-up each patient needs. Recent data suggest
      that mismatch repair mutations confer a greater risk for urothelial cancer.
      Additional large patient series as well as advancement of molecular testing may
      provide triage for Lynch syndrome patients in regards to the frequency and type
      of screening best suited for individual patient.

PMID- 29345161
TI  - Caffeine Improves Triathlon Performance: A Field Study in Males and Females.
AB  - The ergogenic effect of caffeine on endurance exercise is commonly accepted. We
      aimed to elucidate realistically the effect of caffeine on triathlon event
      performance using a field study design, while allowing investigation into
      potential mechanisms at play. A double-blind, randomized, crossover field trial
      was conducted. Twenty-six triathletes (14 males and 12 females; mean +/- SD: age
      = 37.8 +/- 10.6 years, habitual caffeine intake = 413 +/- 505 mg/day, percentage
      body fat = 14.5 +/- 7.2%, and training/week = 12.8 +/- 4.5 hr) participated in
      this study. Microencapsulated caffeine (6 mg/kg body weight) was supplemented 60
      min pretrial. Performance data included time to completion, rating of perceived
      exertion, and profile of mood states. Blood samples taken before, during, and
      postrace were analyzed for cortisol, testosterone, and full blood count.
      Capillary blood lactate concentrations were assessed prerace, during transitions,
      and 3, 6, 9, 12, and 15 min after triathlons. Caffeine supplementation resulted
      in a 3.7% reduction in swim time (33.5 +/- 7.0 vs. 34.8 +/- 8.1 min, p < .05) and
      a 1.3% reduction in time to completion (149.6 +/- 19.8 vs. 151.5 +/- 18.6 min, p
      < .05) for the whole group. Gender differences and individual responses are also
      presented. Caffeine did not alter the rating of perceived exertion significantly,
      but better performance after caffeine supplementation suggests a central effect
      resulting in greater overall exercise intensity at the same rating of perceived
      exertion. Caffeine supplementation was associated with higher postexercise
      cortisol levels (665 +/- 200 vs. 543 +/- 169 nmol/L, p < .0001) and facilitated
      greater peak blood lactate accumulation (analysis of variance main effect, p <
      .05). We recommend that triathlon athletes with relatively low habitual caffeine
      intake may ingest 6 mg/kg body weight caffeine, 45-60 min before the start of
      Olympic-distance triathlon to improve their performance.

PMID- 29345162
TI  - Genetic defect of a combined 17 alpha-hydroxylase/17,20-lyase deficiency patient
      with adrenal crisis.
AB  - Combined 17 alpha-hydroxylase/17,20-lyase deficiency (17OHD) is a rare autosomal
      recessive disease that is a type of congenital adrenal hyperplasia, which results
      in hypertension, hypokalemia, sexual infantilism, primary amenorrhea in females
      (46,XX), or pseudohermaphroditism in males (46,XY). It is mainly caused by
      mutation in the CYP17A1 gene, which encodes a key enzyme in the steroidogenic
      pathway. However, these patients rarely experience adrenal crisis, due to
      abnormally high corticosterone levels. Here, we report a 17OHD patient who
      experienced clinical adrenal crisis on day 1 after gonadectomy. Her (46,XY)
      genetic defect was c0.715 C > T p.Arg239-stop in exon 4 of CYP17A1, which was
      confirmed by targeted sequence capture/high-throughput sequencing and Sanger
      sequencing technology. To the best of our knowledge, 17OHD with adrenal crisis
      has not been reported previously, and the reason why it arose in this patient
      might have been inappropriate glucocorticoid administration during the
      perioperative period.

PMID- 29345163
TI  - Low dose HP-hMG in an antagonist protocol for IVF in ovulatory and anovulatory
      patients with high AMH.
AB  - Women with high-AMH levels have an increased risk of ovarian hyperstimulation
      syndrome (OHSS). Studies have suggested that highly purified menotropin (HP-hMG)
      Menopur(r) reduces the risk. We, therefore, studied use of low-dose (112.5
      IU/day) HP-hMG in ovulatory and anovulatory patients with high AMH (>32 pmol/L).
      The primary endpoint was the distribution of patients with appropriate,
      excessive, and inadequate response (5-14, >=15, and <=4 oocytes). Another
      endpoint was frequency of OHSS. Totally 115 women were included and 78 (67.8%)
      had an appropriate, 8 (7.0%) an excessive, and 29 (25.2%) an inadequate response.
      The number of oocytes was independent on AMH levels and ovulatory status but
      declined significantly with increasing bodyweight (R2 = 0.07, p < .01). The
      ongoing pregnancy rate per started cycle was 47.0%. Three (2.6%) developed OHSS,
      two had cancelation of the cycle and seven patients had GnRH agonist triggering
      to prevent OHSS. Selective use of a low dose of HP-hMG in patients with high
      levels of AMH provides 5-14 oocytes in more than two-thirds of the patients and
      is safe with low risk of OHSS. The number of aspirated oocytes was independent of
      AMH levels and ovulatory status, but inversely related to body weight.

PMID- 29345164
TI  - A positive association between interleukin-1 receptor antagonist and insulin
      resistance in postmenopausal women.
AB  - OBJECTIVE: The purpose of this study was to determine whether higher circulating
      interleukin-1 receptor antagonist (IL-1Ra), an anti-inflammatory cytokine, was
      associated with insulin resistance in postmenopausal women. METHODS: We measured
      IL-1Ra concentrations in 160 naturally postmenopausal women without a history of
      diabetes mellitus. A Pearson coefficient was computed to assess the relationship
      between plasma IL-1Ra and homeostasis model assessment of insulin resistance
      (HOMA-IR). The association between HOMA-IR and IL-1Ra plasma level above the
      median was assessed by logistic regression. Linear regression was used to explore
      the determinants of IL-1Ra plasma levels. RESULTS: A significant positive
      correlation existed between IL-1Ra and HOMA-IR (r = 0.42, p < .0001). The upper
      tertile group of HOMA-IR was associated with approximately 4.5-fold increased
      risk of plasma IL-1Ra level above the median compared with the low-tertile group
      after adjustments. When multiple correlates were entered into the regression
      model simultaneously, only Log HOMA-IR remained significantly related to Log IL
      1Ra (p = .007). CONCLUSIONS: Our results demonstrated a positive association
      between plasma IL-1Ra and insulin resistance in postmenopausal women. This
      analysis suggested that insulin resistance was an important determinant of
      circulating IL-1Ra for these women.

PMID- 29345165
TI  - Oral contraceptive pills as an option for non-surgical management of retained
      products of conception - a preliminary study.
AB  - Many Patients with persistent retained products of conception prefers to avoid
      surgical interventions, such as a dilatation and curettage (D&C) that might pose
      an additional future risk to their already compromised fertility or obstetric
      performance. The aim of this study was to the possibility of induced withdrawal
      bleeding following oral contraceptive administration as a non-surgical treatment
      for patients with persistent retained products of conception (RPOC). A
      retrospective study of patients presenting with retained products of conception
      (RPOC) after failed expectant management or after treatment with PGE1 was
      performed. Twelve women presenting with RPOC at <=8 weeks gestation with minimal
      to mild vaginal bleeding and no signs of infection were treated with oral
      contraceptive pill (OCP) containing 0.03 mg ethinylestradiol and 0.15 mg of
      desogestrel for 3 weeks. Out of the 12 patients treated, nine women (75%)
      successfully expelled the RPOC after completing the three-week course of OCPs.
      The three cases (25%) that did not resolve following OCP treatment had pregnancy
      products with positive blood flow on Doppler examination. We conclude that OCPs
      may be a useful medical treatment option for persisting RPOC in selected patients
      with absence blood flow on Doppler examination wishing to avoid surgical
      intervention.

PMID- 29345166
TI  - Effects of Coffee Components on Muscle Glycogen Recovery: A Systematic Review.
AB  - Coffee is one of the most consumed beverages in the world, and it can improve
      insulin sensitivity, stimulating glucose uptake in skeletal muscle when adequate
      carbohydrate intake is observed. The aim of this review is to analyze the effects
      of coffee and coffee components on muscle glycogen metabolism. A literature
      search was conducted according to Preferred Reporting Items for Systematic
      Reviews and Meta-Analysis, and seven studies were included, that explored the
      effects of coffee components on various substances and signaling proteins. In one
      of the studies with humans, caffeine was shown to increase glucose levels,
      Ca2+/calmodulin-dependent protein kinase phosphorylation, glycogen resynthesis
      rates, and glycogen accumulation after exercise. After intravenous injection of
      caffeine in rats, caffeine increased adenosine monophosphate-activated protein
      kinase (AMPK) and acetyl-CoA carboxylase (ACC) phosphorylation, and glucose
      transport. In in vitro studies, caffeine raised AMPK and ACC phosphorylation,
      increasing glucose transport activity and reducing energy status in rat muscle
      cells. Cafestol and caffeic acid increased insulin secretion in rat beta cells
      and glucose uptake into human muscle cells. Caffeic acid also increased AMPK and
      ACC phosphorylation, reducing the energy status and increasing glucose uptake in
      rat muscle cells. Chlorogenic acid did not show any positive or negative effect.
      The findings from this review must be taken with caution due to the limited
      number of studies on the subject. In conclusion, various coffee components had a
      neutral or positive role in the metabolism of glucose and muscle glycogen,
      whereas no detrimental effect was described. Coffee beverages should be tested as
      an option for athletes' glycogen recovery.

PMID- 29345167
TI  - Dietary Supplements for Health, Adaptation, and Recovery in Athletes.
AB  - Some dietary supplements are recommended to athletes based on data that supports
      improved exercise performance. Other dietary supplements are not ergogenic per
      se, but may improve health, adaptation to exercise, or recovery from injury, and
      so could help athletes to train and/or compete more effectively. In this review,
      we describe several dietary supplements that may improve health, exercise
      adaptation, or recovery. Creatine monohydrate may improve recovery from and
      adaptation to intense training, recovery from periods of injury with extreme
      inactivity, cognitive processing, and reduce severity of or enhance recovery from
      mild traumatic brain injury (mTBI). Omega 3-fatty acid supplementation may also
      reduce severity of or enhance recovery from mTBI. Replenishment of vitamin D
      insufficiency or deficiency will likely improve some aspects of immune, bone, and
      muscle health. Probiotic supplementation can reduce the incidence, duration, and
      severity of upper respiratory tract infection, which may indirectly improve
      training or competitive performance. Preliminary data show that gelatin and/or
      collagen may improve connective tissue health. Some anti-inflammatory
      supplements, such as curcumin or tart cherry juice, may reduce inflammation and
      possibly delayed onset muscle soreness (DOMS). Beta-hydroxy beta-methylbutyrate
      (HMB) does not consistently increase strength and/or lean mass or reduce markers
      of muscle damage, but more research on recovery from injury that includes periods
      of extreme inactivity is needed. Several dietary supplements, including creatine
      monohydrate, omega 3-fatty acids, vitamin D, probiotics, gelatin, and
      curcumin/tart cherry juice could help athletes train and/or compete more
      effectively.

PMID- 29345168
TI  - Mother's age at menopause but not own age at menarche has an impact on ovarian
      reserve.
AB  - To detect clinical parameters impacting ovarian reserve, data were analyzed from
      573 patients who had an anti-Mullerian hormone (AMH) measurement for infertility
      treatment. No impact was found on the age at menarche but a significant
      diminished ovarian reserve was observed when a patient's mother was menopausal
      before age 50. These data suggest that ovarian reserve must be monitored in such
      patients to offer them fertility preservation when at risk of premature ovarian
      insufficiency (POI).

PMID- 29345169
TI  - A case of diffuse large B-cell lymphoma with MYC gene cluster amplification
      related to chromothripsis.

PMID- 29345170
TI  - Cemented total hip replacement in patients under 55 years.
AB  - Background and purpose - About 86,000 total hip replacements (THR) have been
      registered in patients under 55 years in the National Joint Registry of England
      and Wales (NJR). The use of uncemented implants has increased, despite their
      outcomes not having been proven to be significantly better than cemented implants
      in this registry. We determined the implant survivorship and functional outcomes
      of cemented THR in patients under 55 years at a minimum follow-up of 22 years.
      Patients and methods - 104 hips in 100 patients were included in this prospective
      study. Functional outcome was assessed using the Harris Hip Score and radiographs
      were assessed for implant failure and "at risk" of failure. Kaplan-Meier
      survivorship analysis was performed. Results - 89% of hips showed good to
      excellent results at final follow-up with a mean Harris Hip Score of 88 at a mean
      follow-up of 25 years. Revision was performed in 3/104 hips. 14 acetabular
      components and 4 femoral components were "at risk" of failure. The survivorship
      at minimum 22 years with revision for any reason as the end-point was 97% (95% CI
      95-98). Interpretation - Cemented hip replacements perform well in young patients
      with good long-term functional and radiographic outcomes.

PMID- 29345171
TI  - Comparison of Bioelectrical Impedance Analysis and Dual-Energy X-Ray
      Absorptiometry for Estimating Bone Mineral Content.
AB  - The purpose of this study was to validate single-frequency hand-to-foot
      bioelectrical impedance analysis (HFBIA) for estimating bone mineral content
      (BMC) using dual-energy X-ray absorptiometry as the criterion measure in healthy
      men and women aged 18-40 years. A total of 80 men and women participated in this
      study. BMC was estimated on the same day using HFBIA and dual-energy X-ray
      absorptiometry. The HFBIA device provided higher mean BMC values in men and the
      entire sample, but not in women. A smaller standard error of estimate was
      observed in women (0.20, corresponding to 8% of the mean reference BMC values)
      compared with men (0.39, corresponding to 12% of the mean reference BMC values)
      and the combined sample (0.31). HFBIA provided a smaller constant error and
      individual estimation error indicated by the 95% limits of agreement in women (
      0.05 +/- 0.39) compared with men (-0.16 +/- 0.78) and the entire sample (-0.10 +/
      0.63). In conclusion, although BMC values were found to be more accurate in
      women, HFBIA overestimated BMC compared with dual-energy X-ray absorptiometry,
      especially in individuals with lower values. Given these results, using HFBIA to
      measure BMC would be inappropriate for diagnostic purposes.

PMID- 29345172
TI  - Real-world data on first relapse of acute lymphoblastic leukemia in patients >55
      years.

PMID- 29345173
TI  - Effects of Three-Day Serial Sodium Bicarbonate Loading on Performance and
      Physiological Parameters During a Simulated Basketball Test in Female University
      Players.
AB  - The aim of this study was to investigate the effect of 3-day serial sodium
      bicarbonate ingestion on repeated sprint and jump performance. Fifteen female
      university basketball players (23.3 +/- 3.4 years; 173.1 +/- 5.8 cm; 65.8 +/- 6.3
      kg; 23.6 +/- 4.9% body fat) ingested 0.4 g/kg body mass of sodium bicarbonate or
      placebo for 3 days (split in three equal daily doses), before completing a
      simulated basketball exercise. Sprint and circuit times, jump heights,
      performance decrements, and gastrointestinal side effects were recorded during
      the test, and blood lactate concentration was measured pre- and posttest. Sodium
      bicarbonate supplementation led to significant decreases in mean sprint times
      (1.34 +/- 0.23 vs. 1.70 +/- 0.41 s, p = .008, 95% confidence intervals [-0.54, 
      0.10 s]) and mean circuit times (30.6 +/- 2.0 vs. 31.3 +/- 2.0 s, p = .044) and
      significantly greater mean jump height (26.8 [range 25.2-34.2] vs. 26.0 [range
      25.6-33.6] cm, p = .013) compared with placebo. Performance decrement was
      significantly less for sprints with sodium bicarbonate compared with placebo (9.9
      [range 3.4-37.0]% vs. 24.7 [range 4.1-61.3]%, p = .013), but not different for
      jumps (13.1 +/- 4.5% vs. 12.5 +/- 3.1%, p = .321) between conditions. No
      differences in gastrointestinal side effects were noted between conditions.
      Significantly greater postexercise blood lactate concentrations were measured in
      the sodium bicarbonate condition compared with the placebo condition (8.2 +/- 2.8
      vs. 6.6 +/- 2.4 mmol/L, p = .010). This study is the first to show that serial
      loading of sodium bicarbonate is effective for basketball players to improve
      repeated sprint and jump performance during competition, or withstand greater
      training load during practice sessions without any gastrointestinal side effects.

PMID- 29345174
TI  - Using Contemporary Behavior Change Science to Design and Implement an Effective
      Nutritional Intervention Within Professional Rugby League.
AB  - Designing and implementing successful dietary intervention is integral to the
      role of sport nutrition professionals as they attempt to positively change the
      dietary behavior of athletes. High-performance sport is a time-pressured
      environment where immediate results can often supersede pursuit of the most
      effective evidence-based practice. However, efficacious dietary intervention
      necessitates comprehensive, systematic, and theoretical behavioral design and
      implementation, if the habitual dietary behaviors of athletes are to be
      positively changed. Therefore, this case study demonstrates how the Behaviour
      Change Wheel was used to design and implement an effective nutritional
      intervention within a professional rugby league. The eight-step intervention
      targeted athlete consumption of a high-quality dietary intake of 25.1 MJ each day
      to achieve an overall body mass increase of 5 kg across a 12-week intervention
      period. The capability, opportunity, motivation, and behavior model and
      affordability, practicability, effectiveness/cost-effectiveness, acceptability,
      safety, and equity criteria were used to identify population-specific
      intervention functions, policy categories, behavior change techniques, and modes
      of intervention delivery. The resulting intervention was successful, increasing
      the average daily energy intake of the athlete to 24.5 MJ, which corresponded in
      a 6.2 kg body mass gain. Despite consuming 0.6 MJ less per day than targeted,
      secondary outcome measures of diet quality, strength, body composition, and
      immune function all substantially improved, supporting sufficient energy intake
      and the overall efficacy of a behavioral approach. Ultimately, the Behaviour
      Change Wheel provides sport nutrition professionals with an effective and
      practical stepwise method to design and implement effective nutritional
      interventions for use within high-performance sport.

PMID- 29345175
TI  - A role for bone turnover markers beta-CrossLaps (CTX) and amino-terminal
      propeptide of type I collagen (PINP) as potential indicators for disease
      progression from MGUS to multiple myeloma.
AB  - Multiple myeloma (MM) is characterized by bone lesions arising due to unbalanced
      bone remodeling. Changes in the bone formation marker amino-terminal propeptide
      of type I collagen (PINP) and the bone resorption marker beta-CrossLaps (CTX)
      reflect physiologic bone turnover. Whether PINP and CTX have a role in disease
      progression from monoclonal gammopathy of undetermined significance (MGUS) to MM
      is unknown. In this cross-sectional follow-up study, 241 patients with MM or MGUS
      were included. Serum levels of PINP and CTX were significantly higher in MM
      patients compared to MGUS. Moreover, increasing concentrations of PINP and CTX
      were observed in those MGUS patients progressing to MM, whereas PINP and CTX
      levels remained unchanged in MGUS patients with stable disease. In conclusion,
      these data indicate a potential role of PINP and CTX as biomarkers for the
      progression of MGUS to MM.

PMID- 29345177
TI  - Prognostic significance of cathepsin L expression in pediatric acute myeloid
      leukemia.
AB  - Overexpression of cathepsin L (CTSL), an endolysosomal cysteine protease, is
      associated with inferior survival of patients with various human malignancies. We
      evaluated the expression/activity of CTSL in peripheral blood mononuclear cells
      (PBMCs) and bone marrow mononuclear cells (BMMCs) of 103 pediatric acute myeloid
      leukemia (AML) patients to assess its prognostic significance in this malignancy.
      Thirty-five healthy siblings of patients served as controls. Our results revealed
      significantly higher CTSL activity (p < .0001), protein (p < .05), and mRNA
      levels (p < .01) in both PBMCs and BMMCs of patients as compared with controls.
      BMMCs displayed higher activity of CTSL than PBMCs (p < .01). A dramatic
      reduction in CTSL activity was recorded after chemotherapy in a significant
      proportion (74%) of patients (p < .0001). By multivariate analysis, CTSL in BMMCs
      emerged as a strong independent prognostic marker for overall survival (OS) (p =
      .004). Thus, our results suggest the potential utility of CTSL in predicting the
      outcome of pediatric AML.

PMID- 29345176
TI  - Bone marrow VEGFC expression is associated with multilineage dysplasia and
      several prognostic markers in adult acute myeloid leukemia, but not with
      survival.
AB  - Vascular endothelial growth factor C (VEGFC) stimulates leukemia cell
      proliferation and survival, and promotes angiogenesis. We studied VEGFC
      expression in bone marrow samples from 353 adult acute myeloid leukemia (AML)
      patients and its relationship with several clinical, cytogenetic, and molecular
      variables. We also studied the expression of 84 genes involved in VEGF signaling
      in 24 patients. We found that VEGFC expression was higher in AML patients with
      myelodysplasia-related changes (AML-MRC) than in patients with non-AML-MRC. We
      also found an association between VEGFC expression and the patient cytogenetic
      risk group, with those with a worse prognosis having higher VEGFC expression
      levels. No correlation was observed between VEGFC expression and survival or
      complete remission. VEGFC expression strongly correlated with expression of the
      VEGF receptors FLT1, KDR, and NRP1. Thus, in this series, VEGFC expression was
      increased in AML-MRC and in subgroups with a poorer prognosis, but has no impact
      on survival.

PMID- 29345178
TI  - Frequency and Factors Associated With Honorary Authorship in Indian Biomedical
      Journals: Analysis of Papers Published From 2012 to 2013.
AB  - Honorary authorship is the inclusion of an author on an article whose
      contribution does not warrant authorship. We conducted an Internet-based survey
      among first authors publishing in Indian biomedical journals from 2012 to 2013 to
      study the frequency and factors associated with honorary authorship. The response
      rate was 27% (245/908) with the prevalence of perceived, International Committee
      of Medical Journal Editors (ICMJE)-defined, and unperceived honorary authorship
      of 20.9% (50/239), 60% (147/245), and 46.9% (115/245), respectively. Those
      residing in India were found to list more honorary authors. We hope to increase
      awareness of the ICMJE authorship guidelines and the general issue of honorary
      authorship among researchers in India and elsewhere.

PMID- 29345179
TI  - Regulatory Support Improves Subsequent IRB Approval Rates in Studies Initially
      Deemed Not Ready for Review: A CTSA Institution's Experience.
AB  - We evaluated the impact of a regulatory support service (known as the Regulatory
      Knowledge and Support [RKS] program), part of the Medical University of South
      Carolina's Clinical and Translational Science Award, on the success of
      Institutional Review Board (IRB) applications that have previously been deemed by
      the IRB to be Not Ready for Review (NRR). At the time of this evaluation, 77
      studies had been deemed NRR, 53 of which came from trainees and junior faculty.
      All the applications that received regulatory support either received IRB
      approval or were deemed to not be research, and therefore did not require IRB
      review. In all, 39.1% (n = 18) of the research teams who did not accept
      regulatory support successfully received IRB approval. Providing regulatory
      support, particularly to trainees and junior faculty, may be associated with
      better success in obtaining IRB approval as well as preventing the unnecessary
      submission of projects that are not research and would therefore not require IRB
      review or approval.

PMID- 29345181
TI  - Corrigendum.

PMID- 29345180
TI  - Depression Among Caregivers of Patients With Dementia.
AB  - We aimed to assess depressive symptoms in caregivers of patients with dementia,
      taking into account variables such as severity of dementia, sex, age, and
      financial state of the patient. We recruited 222 caregivers of patients with
      dementia from King Abdulaziz Medical City, Saudi Alzheimer's Disease Association,
      and online, from February to June 2017, and employed the Patient Health
      Questionnaire to assess depression, and the Blessed Dementia Scale to assess
      severity of dementia. The prevalence of clinical depression among the caregivers
      was 14.9%. Minimal symptoms of depression were experienced by 96 caregivers
      (43.2%), moderate by 45 (20.3%), moderate-severe by 15 (6.8%), and severe by 8
      (3.6%). Forty-six patients had mild dementia (22%), 73 had moderate (34.9%), and
      90 had severe (43.1%). Caregivers of patients with dementia experience
      considerable burden and lower level of health-related quality of life and may be
      predisposed to developing clinical depression.

PMID- 29345182
TI  - Breast cancer screening among shift workers: a nationwide population-based survey
      in Korea.
AB  - We aimed to examine the association between shift work types and participation in
      breast cancer screening (BCS) programs by comparing rates of participation for
      BCS among regular daytime workers and alternative shift workers using data from a
      nationally representative, population-based survey conducted in Korea. In
      addition, the results were analyzed according to sociodemographic factors,
      including occupation, education, income, private health insurance, age, and
      number of working hours a week. This secondary cross-sectional analysis used data
      from the 2012 Korean National Health and Nutritional Examination Survey. The
      target population included women aged >= 40 years who responded as to whether
      they had undergone BCS in the previous year. Accordingly, we analyzed survey data
      for a total of 1,193 women and used a multivariate logistic regression analysis
      to evaluate the differences in factors affecting BCS between regular daytime and
      alternative shift workers. A logistic regression analysis was performed
      considering private health insurance as a significant sociodemographic factor for
      BCS among regular daytime shift workers. In contrast, none of the tested
      variables could significantly predict adherence to BCS among alternative shift
      workers. The results of this study suggest the need for the development of
      comprehensive workplace breast cancer prevention programs by considering shift
      work types. More attention should be given to female workers with low education
      levels, those who are uninsured, and young workers to improve the participation
      rate for BCS at the workplace.

PMID- 29345184
TI  - Temperature-dependent small RNA expression in Drosophila melanogaster.
AB  - Temperature has a major impact on gene expression in ectotherms. But until
      recently, it was not clear in which way, if any, small non-coding RNAs such as
      miRNAs or piRNAs contribute to thermosensitive gene regulation. We have recently
      shown that temperature-responsive miRNAs in Drosophila drive adaptation to
      different ambient temperatures on the transcriptome level. Moreover, we
      demonstrated that higher temperatures lead to a more efficient piRNA-dependent
      transposon silencing, possibly due to heat-induced unfolding of RNA secondary
      structures. In this commentary, we will dwell upon particular interesting aspects
      connected to our findings, hoping that our point of view may encourage other
      scientists to address some of the questions raised here. We will particularly
      focus on aspects related to climate-dependent transposon propagation in evolution
      and putative transgenerational epigenetic effects of altered small RNA
      transcriptomes. We further briefly indicate how temperature-responsive miRNAs may
      confound the interpretation of data obtained from experiments comprising heat
      shock treatment which is a widely used technique not only in Drosophila genetics.

PMID- 29345186
TI  - Response to Commentary: Regulatory Support Improves Subsequent IRB Approval Rates
      in Studies Initially Deemed Not Ready for Review-A CTSA Institution's Experience.

PMID- 29345187
TI  - The formation of a medical student research committee and its impact on
      involvement in departmental research.
AB  - : Over the past ten years, medical students have increased their research
      activity to be competitive for orthopaedic residency positions throughout the
      country. This increase may favor students at institutions with a strong history
      of research production and well-established research departments with supporting
      staff. To compete with these institutions, a Musculoskeletal Research Committee
      was developed at a southern academic institution to provide a mutually beneficial
      link between orthopaedic research faculty and medical students. This manuscript
      describes the formation of this committee and the resultant involvement of young
      medical students in departmental research over a one year period. Composed of
      students and faculty, the committee developed a Research Guide for Medical
      Students, Research Database and Student List, Medical Students' Webpage, and
      Routing Form, and holds quarterly meetings for those students active in
      orthopaedic research. With this platform, the committee aimed to increase young
      student involvement in research and provide a stratified level of study
      participation among upper-level students for continued mentorship. In one
      calendar year, the total number of first and second-year students participating
      in department research increased 460% (5 to 28). Also, the total number of
      research projects with student involvement from these two classes increased 780%
      (5 to 44). The introduction of a research committee is an effective method of
      stimulating student interest in departmental research. Early participation
      results are promising, and this method may be applicable to other departments and
      institutions hoping to increase research productivity. ABBREVIATIONS: IRB:
      Institutional Review Board.

PMID- 29345188
TI  - Arsenic removal from alkaline leaching solution using Fe (III) precipitation.
AB  - The alkaline leaching solution from arsenic-containing gold concentrate contains
      a large amount of arsenate ions, which should be removed because it is harmful to
      the production process and to the environment. In this study, conventional Fe
      (III) precipitation was used to remove arsenic from the leaching solution. The
      precipitation reaction was carried out at the normal temperature, and the effects
      of pH value and Fe/As ratio on the arsenic removal were investigated. The results
      show that the removal rate of arsenic is distinctive at different pH values, and
      the effect is best within the pH range of 5.25-5.96. The removal rate can be
      further increased by increasing the ratio of Fe/As. When the pH = 5.25-5.96 and
      Fe/As > 1.8, the arsenic in the solution can be reduced to below 5 mg/L. However,
      the crystallinity of ferric arsenate is poor, and the particle size is small,
      most of which is about 1 MUm. The leaching toxicity test shows the leaching
      toxicity of precipitates gradually decreased by the increase of Fe/As. The
      precipitates can be stored safely as the ratio of Fe/As exceeded 2.5.

PMID- 29345185
TI  - Drugging tRNA aminoacylation.
AB  - Inhibition of tRNA aminoacylation has proven to be an effective antimicrobial
      strategy, impeding an essential step of protein synthesis. Mupirocin, the well
      known selective inhibitor of bacterial isoleucyl-tRNA synthetase, is one of three
      aminoacylation inhibitors now approved for human or animal use. However, design
      of novel aminoacylation inhibitors is complicated by the steadfast requirement to
      avoid off-target inhibition of protein synthesis in human cells. Here we review
      available data regarding known aminoacylation inhibitors as well as key amino
      acid residues in aminoacyl-tRNA synthetases (aaRSs) and nucleotides in tRNA that
      determine the specificity and strength of the aaRS-tRNA interaction. Unlike most
      ligand-protein interactions, the aaRS-tRNA recognition interaction represents
      coevolution of both the tRNA and aaRS structures to conserve the specificity of
      aminoacylation. This property means that many determinants of tRNA recognition in
      pathogens have diverged from those of humans-a phenomenon that provides a
      valuable source of data for antimicrobial drug development.

PMID- 29345189
TI  - MicroRNA-19 contributes to the malignant phenotypes of osteosarcoma in vitro by
      targeting Pax6.
AB  - This study was conducted to detect the expression of miR-19 and Pax6 (Paired box
      protein 6) in human osteosarcoma cells and the effects on biological
      characteristics of osteosarcoma cells. Quantitative real-time polymerase chain
      reaction was used to detect the expression of Pax6 and miR-19 in normal human
      osteoblasts (hFOB 1.19) and osteosarcoma cell lines (U2OS, Saos-2, and MG-63).
      Results showed that miR-19 was significantly upregulated in osteosarcoma cell
      lines compared with that in hFOB 1.19 cells, while the expression of Pax6
      messenger RNA was significantly downregulated. Pax6 was defined as the target
      gene of miR-19 which was validated by luciferase reporter gene analysis. Results
      indicated that miR-19 had an interaction with Pax6 3'-untranslated region. At the
      same time, the protein expression of Pax6 was significantly decreased in the MG
      63 cells transfected with miR-19 mimic and was notably enhanced in osteosarcoma
      MG-63 cells transfected with miR-19 inhibitor. These data suggested that Pax6 was
      a target of miR-19 in osteosarcoma MG-63 cells. The effects of miR-19 on the
      biological behavior of MG-63 cells were determined by 3-(4,5-dimethylthiazol-2
      yl)-2,5-diphenyltetrazolium bromide, flow cytometry, and Transwell assay. Results
      showed that the downregulation of miR-19 inhibited cell viability, reduced the
      percentage of cells in S phase and the number of cells passing through the
      Transwell chamber, and increased the number of apoptotic cells. Western blot
      analysis showed that the inhibition of miR-19 significantly increased the
      expression of epithelial proteins (E-cadherin and beta-catenin) and decreased the
      expression of mesenchymal protein (Vimentin), extracellular signal-regulated
      kinase, and phosphorylated extracellular signal-regulated kinase in MG-63 cells.
      MiR-19 inhibitor and Pax6 small interfering RNA were simultaneously transfected
      into MG-63 cells. Results from 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide, flow cytometry, and Transwell assay demonstrated
      that the inhibition of Pax6 expression in MG-63 cells could reverse the cell
      biological effects induced by the inhibition of miR-19 expression. Based on these
      findings, it was suggested that miR-19, upregulated in osteosarcoma cells,
      negatively regulated the expression of Pax6, which can promote the malignant
      phenotypes of osteosarcoma cells via activation of the extracellular signal
      regulated kinase signaling pathways. Therefore, miR-19/Pax6 may offer potential
      for use as a target for the treatment of osteosarcoma.

PMID- 29345191
TI  - Enhanced sulfide removal and bioelectricity generation in microbial fuel cells
      with anodes modified by vertically oriented nanosheets.
AB  - Anode materials and structures are of critical importance for microbial fuel
      cells (MFCs) recovering energy from toxic substrates. Carbon-fiber-felt anodes
      modified by layers of vertically oriented TiO2 and Fe2O3 nanosheets were applied
      in the present study. Enhanced sulfide removal efficiencies (both over 90%) were
      obtained after a 48-h operation, with maximum power densities improved by 1.53
      and 1.36 folds compared with MFCs with raw carbon-fiber-felt anode. The modified
      anodes provided more active sites for microbial adhesion with increasing biomass
      densities. High-throughput 16S rRNA gene sequencing analysis also indicated the
      increase in microbial diversities. Bacteroidetes responsible for bioelectricity
      generation with Thiobacillus and Spirochaeta dominating sulfide removal were
      found in the MFCs with the modified anodes, with less anaerobic fermentative
      bacteria as Firmicutes appeared. This indicates that the proposed materials are
      competitive for applications of MFCs generating bioelectricity from toxic
      sulfide.

PMID- 29345190
TI  - Magnetoelectric nanoparticles for delivery of antitumor peptides into
      glioblastoma cells by magnetic fields.
AB  - AIM: We studied externally controlled anticancer effects of binding tumor growth
      inhibiting synthetic peptides to magnetoelectric nanoparticles (MENs) on
      treatment of glioblastomas. METHODS: Hydrothermally synthesized 30-nm MENs had
      the core-shell composition of CoFe2O4@BaTiO3. Molecules of growth hormone
      releasing hormone antagonist of the MIA class (MIA690) were chemically bound to
      MENs. In vitro experiments utilized human glioblastoma cells (U-87MG) and human
      brain microvascular endothelial cells. RESULTS: The studies demonstrated
      externally controlled high-efficacy binding of MIA690 to MENs, targeted
      specificity to glioblastoma cells and on-demand release of the peptide by
      application of d.c. and a.c. magnetic fields, respectively. CONCLUSION: The
      results support the use of MENs as an effective drug delivery carrier for growth
      hormone-releasing hormone antagonists in the treatment of human glioblastomas.

PMID- 29345192
TI  - Cross-validation of the Dot Counting Test in a large sample of credible and non
      credible patients referred for neuropsychological testing.
AB  - OBJECTIVE: To cross-validate the Dot Counting Test in a large neuropsychological
      sample. METHOD: Dot Counting Test scores were compared in credible (n = 142) and
      non-credible (n = 335) neuropsychology referrals. RESULTS: Non-credible patients
      scored significantly higher than credible patients on all Dot Counting Test
      scores. While the original E-score cut-off of >=17 achieved excellent specificity
      (96.5%), it was associated with mediocre sensitivity (52.8%). However, the cut
      off could be substantially lowered to >=13.80, while still maintaining adequate
      specificity (>=90%), and raising sensitivity to 70.0%. Examination of non
      credible subgroups revealed that Dot Counting Test sensitivity in feigned mild
      traumatic brain injury (mTBI) was 55.8%, whereas sensitivity was 90.6% in
      patients with non-credible cognitive dysfunction in the context of claimed
      psychosis, and 81.0% in patients with non-credible cognitive performance in
      depression or severe TBI. Thus, the Dot Counting Test may have a particular role
      in detection of non-credible cognitive symptoms in claimed psychiatric disorders.
      Alternative to use of the E-score, failure on >=1 cut-offs applied to individual
      Dot Counting Test scores (>=6.0" for mean grouped dot counting time, >=10.0" for
      mean ungrouped dot counting time, and >=4 errors), occurred in 11.3% of the
      credible sample, while nearly two-thirds (63.6%) of the non-credible sample
      failed one of more of these cut-offs. CONCLUSIONS: An E-score cut-off of 13.80,
      or failure on >=1 individual score cut-offs, resulted in few false positive
      identifications in credible patients, and achieved high sensitivity (64.0-70.0%),
      and therefore appear appropriate for use in identifying neurocognitive
      performance invalidity.

PMID- 29345193
TI  - Serotonin 2A receptor inhibition protects against the development of pulmonary
      hypertension and pulmonary vascular remodeling in neonatal mice.
AB  - Pulmonary hypertension (PH) complicating bronchopulmonary dysplasia (BPD) worsens
      clinical outcomes in former preterm infants. Increased serotonin (5
      hydroxytryptamine, 5-HT) signaling plays a prominent role in PH pathogenesis and
      progression in adults. We hypothesized that increased 5-HT signaling contributes
      to the pathogenesis of neonatal PH, complicating BPD and neonatal lung injury.
      Thus, we investigated 5-HT signaling in neonatal mice exposed to bleomycin,
      previously demonstrated to induce PH and alveolar simplification. Newborn wild
      type mice received intraperitoneal PBS, ketanserin (1 mg/kg), bleomycin (3 U/kg)
      or bleomycin (3 U/kg) plus ketanserin (1 mg/kg) three times weekly for 3 wk.
      Following treatment with bleomycin, pulmonary expression of the rate-limiting
      enzyme of 5-HT synthesis, tryptophan hydroxylase-1 (Tph1), was significantly
      increased. Bleomycin did not affect pulmonary 5-HT 2A receptor (R) expression,
      but did increase pulmonary gene expression of the 5-HT 2BR and serotonin
      transporter. Treatment with ketanserin attenuated bleomycin-induced PH (increased
      RVSP and RVH) and pulmonary vascular remodeling (decreased vessel density and
      increased muscularization of small vessels). In addition, we found that treatment
      with ketanserin activated pulmonary MAPK and Akt signaling in mice exposed to
      bleomycin. We conclude that 5-HT signaling is increased in a murine model of
      neonatal PH and pharmacological inhibition of the 5-HT 2AR protects against the
      development of PH in neonatal lung injury. We speculate this occurs through
      restoration of MAPK signaling and increased Akt signaling.

PMID- 29345194
TI  - Transient stretch induces cytoskeletal fluidization through the severing action
      of cofilin.
AB  - With every deep inspiration (DI) or sigh, the airway wall stretches, as do the
      airway smooth muscle cells in the airway wall. In response, the airway smooth
      muscle cell undergoes rapid stretch-induced cytoskeletal fluidization. As a
      molecular mechanism underlying the cytoskeletal fluidization response, we
      demonstrate a key role for the actin-severing protein cofilin. Using primary
      human airway smooth muscle cells, we simulated a DI by imposing a transient
      stretch of physiological magnitude and duration. We used traction microscopy to
      measure the resulting changes in contractile forces. After a transient stretch,
      cofilin-knockdown cells exhibited a 29 +/- 5% decrease in contractile force
      compared with prestretch conditions. By contrast, control cells exhibited a 67 +/
      6% decrease ( P < 0.05, knockdown vs. control). Consistent with these
      contractile force changes with transient stretch, actin filaments in cofilin
      knockdown cells remained largely intact, whereas actin filaments in control cells
      were rapidly disrupted. Furthermore, in cofilin-knockdown cells, contractile
      force at baseline was higher and rate of remodeling poststretch was slower than
      in control cells. Additionally, the severing action of cofilin was restricted to
      the release phase of the transient stretch. We conclude that the actin-severing
      activity of cofilin is an important factor in stretch-induced cytoskeletal
      fluidization and may account for an appreciable part of the bronchodilatory
      effects of a DI.

PMID- 29345196
TI  - Surfactant protein C dampens inflammation by decreasing JAK/STAT activation
      during lung repair.
AB  - Surfactant protein C (SPC), a key component of pulmonary surfactant, also plays a
      role in regulating inflammation. SPC deficiency in patients and mouse models is
      associated with increased inflammation and delayed repair, but the key drivers of
      SPC-regulated inflammation in response to injury are largely unknown. This study
      focuses on a new mechanism of SPC as an anti-inflammatory molecule using SPC
      TK/SPC-KO (surfactant protein C-thymidine kinase/surfactant protein C knockout)
      mice, which represent a novel sterile injury model that mimics clinical acute
      respiratory distress syndrome (ARDS). SPC-TK mice express the inducible suicide
      gene thymidine kinase from by the SPC promoter, which targets alveolar type 2
      (AT2) cells for depletion in response to ganciclovir (GCV). We compared GCV
      induced injury and repair in SPC-TK mice that have normal endogenous SPC
      expression with SPC-TK/SPC-KO mice lacking SPC expression. In contrast to SPC-TK
      mice, SPC-TK/SPC-KO mice treated with GCV exhibited more severe inflammation,
      resulting in over 90% mortality; there was only 8% mortality of SPC-TK animals.
      SPC-TK/SPC-KO mice had highly elevated inflammatory cytokines and granulocyte
      infiltration in the bronchoalveolar lavage (BAL) fluid. Consistent with a
      proinflammatory phenotype, immunofluorescence revealed increased phosphorylated
      signal transduction and activation of transcription 3 (pSTAT3), suggesting
      enhanced Janus kinase (JAK)/STAT activation in inflammatory and AT2 cells of SPC
      TK/SPC-KO mice. The level of suppressor of cytokine signaling 3, an anti
      inflammatory mediator that decreases pSTAT3 signaling, was significantly
      decreased in the BAL fluid of SPC-TK/SPC-KO mice. Hyperactivation of pSTAT3 and
      inflammation were rescued by AZD1480, a JAK1/2 inhibitor. Our findings showing a
      novel role for SPC in regulating inflammation via JAK/STAT may have clinical
      applications.

PMID- 29345197
TI  - Neonatal hyperoxia depletes pulmonary vein cardiomyocytes in adult mice via
      mitochondrial oxidation.
AB  - Supplemental oxygen given to preterm infants has been associated with permanently
      altering postnatal lung development. Now that these individuals are reaching
      adulthood, there is growing concern that early life oxygen exposure may also
      promote cardiovascular disease through poorly understood mechanisms. We
      previously reported that adult mice exposed to 100% oxygen between postnatal days
      0 and 4 develop pulmonary hypertension, defined pathologically by capillary
      rarefaction, dilation of arterioles and veins, cardiac failure, and a reduced
      lifespan. Here, Affymetrix Gene Arrays are used to identify early transcriptional
      changes that take place in the lung before pulmonary capillary rarefaction. We
      discovered neonatal hyperoxia reduced expression of cardiac muscle genes,
      including those involved in contraction, calcium signaling, mitochondrial
      respiration, and vasodilation. Quantitative RT-PCR, immunohistochemistry, and
      genetic lineage mapping using Myh6CreER; Rosa26RmT/mG mice revealed this
      reflected loss of pulmonary vein cardiomyocytes. The greatest loss of
      cadiomyocytes was seen within the lung followed by a graded loss beginning at the
      hilum and extending into the left atrium. Loss of these cells was seen by 2 wk of
      age in mice exposed to >=80% oxygen and was attributed, in part, to reduced
      proliferation. Administering mitoTEMPO, a scavenger of mitochondrial superoxide
      during neonatal hyperoxia prevented loss of these cells. Since pulmonary vein
      cardiomyocytes help pump oxygen-rich blood out of the lung, their early loss
      following neonatal hyperoxia may contribute to cardiovascular disease seen in
      these mice, and perhaps in people who were born preterm.

PMID- 29345195
TI  - Mitochondrial dysfunction and pulmonary hypertension: cause, effect, or both.
AB  - Pulmonary hypertension describes a heterogeneous disease defined by increased
      pulmonary artery pressures, and progressive increase in pulmonary vascular
      resistance due to pathologic remodeling of the pulmonary vasculature involving
      pulmonary endothelial cells, pericytes, and smooth muscle cells. This process
      occurs under various conditions, and although these populations vary, the
      clinical manifestations are the same: progressive dyspnea, increases in right
      ventricular (RV) afterload and dysfunction, RV-pulmonary artery uncoupling, and
      right-sided heart failure with systemic circulatory collapse. The overall
      estimated 5-yr survival rate is 72% in highly functioning patients, and as low as
      28% for those presenting with advanced symptoms. Metabolic theories have been
      suggested as underlying the pathogenesis of pulmonary hypertension with growing
      evidence of the role of mitochondrial dysfunction involving the major proteins of
      the electron transport chain, redox-related enzymes, regulators of the proton
      gradient and calcium homeostasis, regulators of apoptosis, and mitophagy. There
      remain more studies needed to characterize mitochondrial dysfunction leading to
      impaired vascular relaxation, increase proliferation, and failure of regulatory
      mechanisms. The effects on endothelial cells and resulting interactions with
      their microenvironment remain uncharted territory for future discovery.
      Additionally, on the basis of observations that the "plexigenic lesions" of
      pulmonary hypertension resemble the unregulated proliferation of tumor cells,
      similarities between cancer pathobiology and pulmonary hypertension have been
      drawn, suggesting interactions between mitochondria and angiogenesis. Recently,
      mitochondria targeting has become feasible, which may yield new therapeutic
      strategies. We present a state-of-the-art review of the role of mitochondria in
      both the pathobiology of pulmonary hypertension and potential therapeutic targets
      in pulmonary vascular processes.

PMID- 29345199
TI  - Pulmonary vascular dysfunction secondary to pulmonary arterial hypertension:
      insights gained through retrograde perfusion.
AB  - Here, we tested the hypothesis that severe pulmonary arterial hypertension
      impairs retrograde perfusion. To test this hypothesis, pulmonary arterial
      hypertension was induced in Fischer rats using a single injection of Sugen 5416
      followed by 3 wk of exposure to 10% hypoxia and then 2 wk of normoxia. This Sugen
      5416 and hypoxia regimen caused severe pulmonary arterial hypertension, with a
      Fulton index of 0.73 +/- 0.07, reductions in both the pulmonary arterial
      acceleration time and pulmonary arterial acceleration to pulmonary arterial
      ejection times ratio, and extensive medial hypertrophy and occlusive neointimal
      lesions. Whereas the normotensive circulation accommodated large increases in
      forward and retrograde flow, the hypertensive circulation did not. During forward
      flow, pulmonary artery and double occlusion pressures rose sharply at low
      perfusion rates, resulting in hydrostatic edema. Pulmonary arterial hypertensive
      lungs possessed an absolute intolerance to retrograde perfusion, and they rapidly
      developed edema. Retrograde perfusion was not rescued by maximal vasodilation.
      Retrograde perfusion was preserved in lungs from animals treated with Sugen 5416
      and hypoxia for 1 and 3 wk, in lungs from animals with a milder form of hypoxic
      hypertension, and in normotensive lungs subjected to high outflow pressures. Thus
      impaired retrograde perfusion coincides with development of severe pulmonary
      arterial hypertension, with advanced structural defects in the microcirculation.

PMID- 29345200
TI  - Distinct niches within the extracellular matrix dictate fibroblast function in
      (cell free) 3D lung tissue cultures.
AB  - Cues from the extracellular matrix (ECM) and their functional interplay with
      cells play pivotal roles for development, tissue repair, and disease. However,
      the precise nature of this interplay remains elusive. We used an innovative 3D
      cell culture ECM model by decellularizing 300-um-thick ex vivo lung tissue
      scaffolds (d3D-LTCs) derived from diseased and healthy mouse lungs, which widely
      mimics the native (patho)physiological in vivo ECM microenvironment. We
      successfully repopulated all d3D-LTCs with primary human and murine fibroblasts,
      and moreover, we demonstrated that the cells also populated the innermost core
      regions of the d3D-LTCs in a real 3D fashion. The engrafted fibroblasts revealed
      a striking functional plasticity, depending on their localization in distinct ECM
      niches of the d3D-LTCs, affecting the cells' tissue engraftment, cellular
      migration rates, cell morphologies, and protein expression and phosphorylation
      levels. Surprisingly, we also observed fibroblasts that were homing to the lung
      scaffold's interstitium as well as fibroblasts that were invading fibrotic areas.
      To date, the functional nature and even the existence of 3D cell matrix adhesions
      in vivo as well as in 3D culture models is still unclear and controversial. Here,
      we show that attachment of fibroblasts to the d3D-LTCs evidently occurred via
      focal adhesions, thus advocating for a relevant functional role in vivo.
      Furthermore, we found that protein levels of talin, paxillin, and zyxin and
      phosphorylation levels of paxillin Y118, as well as the migration-relevant small
      GTPases RhoA, Rac, and CDC42, were significantly reduced compared with their
      attachment to 2D plastic dishes. In summary, our results strikingly indicate that
      inherent physical or compositional characteristics of the ECM act as instructive
      cues altering the functional behavior of engrafted cells. Thus, d3D-LTCs might
      aid to obtain more realistic data in vitro, with a high relevance for drug
      discovery and mechanistic studies alike.

PMID- 29345198
TI  - Fibrin turnover and pleural organization: bench to bedside.
AB  - Recent studies have shed new light on the role of the fibrinolytic system in the
      pathogenesis of pleural organization, including the mechanisms by which the
      system regulates mesenchymal transition of mesothelial cells and how that process
      affects outcomes of pleural injury. The key contribution of plasminogen activator
      inhibitor-1 to the outcomes of pleural injury is now better understood as is its
      role in the regulation of intrapleural fibrinolytic therapy. In addition, the
      mechanisms by which fibrinolysins are processed after intrapleural administration
      have now been elucidated, informing new candidate diagnostics and therapeutics
      for pleural loculation and failed drainage. The emergence of new potential
      interventional targets offers the potential for the development of new and more
      effective therapeutic candidates.

PMID- 29345201
TI  - Clinical validation of nuclear factor kappa B expression in invasive breast
      cancer.
AB  - Breast cancer is the most commonly diagnosed cancer in Polish women. The
      expression of transcription nuclear factor kappa B, a key inducer of inflammatory
      response promoting carcinogenesis and cancer progression in breast cancer, is not
      well-established. We assessed the nuclear factor kappa B expression in a total of
      119 invasive breast carcinomas and 25 healthy control samples and correlated this
      expression pattern with several clinical and pathologic parameters including
      histologic type and grade, tumor size, lymph node status, estrogen receptor
      status, and progesterone receptor status. The data used for the analysis were
      derived from medical records. An immunohistochemical analysis of nuclear factor
      kappa B, estrogen receptor, and progesterone receptor was carried out and
      evaluation of stainings was performed. The expression of nuclear factor kappa B
      was significantly higher than that in the corresponding healthy control samples.
      No statistical difference was demonstrated in nuclear factor kappa B expression
      in relation to age, menopausal status, lymph node status, tumor size and
      location, grade and histologic type of tumor, and hormonal status (estrogen
      receptor and progesterone receptor). Nuclear factor kappa B is significantly
      overexpressed in invasive breast cancer tissues. Although nuclear factor kappa B
      status does not correlate with clinicopathological findings, it might provide
      important additional information on prognosis and become a promising object for
      targeted therapy.

PMID- 29345202
TI  - Qualitative and semiquantitative analysis of the protein coronas associated to
      different functionalized nanoparticles.
AB  - AIM: The investigation on protein coronas (PCs) adsorbed onto nanoparticle (NP)
      surface is representing an open issue due to difficulties in detection and clear
      isolation of the adsorbed proteins. In this study, we investigated protocols able
      to isolate the compositions of PCs of three polymeric NPs. MATERIALS & METHODS:
      Unfunctionalized NPs and two functionalized NPs were considered as proof-of
      concept for the qualitative and semiquantitative analysis of both the corona
      levels (stably or weakly adsorbed coronas [SC/WC]) of these different
      nanocarriers. RESULTS: The protocols applied were able to discriminate between
      the SC and WC. In particular, experimental results indicated that stably adsorbed
      coronas are prevalently composed by ApoE, while WC by albumin in all the NPs.
      Otherwise, some differences in WC could be correlated with surface
      functionalization. CONCLUSION: This experimental approach allows characterizing
      the whole PCs, proposing a protocol for isolation of different types of proteins
      composing PCs.

PMID- 29345203
TI  - Illusionary Science?

PMID- 29345205
TI  - Update on Lateral Ankle Instability.

PMID- 29345206
TI  - Successful treatment of refractory autoimmune hemolytic anemia after allogeneic
      hematopoietic stem cell transplantation with bortezomib.

PMID- 29345208
TI  - Top-rated AMEE MedEdPublish Papers - September 2017.

PMID- 29345207
TI  - Thresholds and interpretations: How clinical competency committees identify
      pediatric residents with performance concerns.
AB  - BACKGROUND: Clinical competency committee (CCC) identification of residents with
      performance concerns is critical for early intervention. METHODS: Program
      directors and 94 CCC members at 14 pediatric residency programs responded to a
      written survey prompt asking them to describe how they identify residents with
      performance concerns. Data was analyzed using thematic analysis. RESULTS: Six
      themes emerged from analysis and were grouped into two domains. The first domain
      included four themes, each describing a path through which residents could meet
      or exceed a concern threshold:1) written comments from rotation assessments are
      foundational in identifying residents with performance concerns, 2) concerning
      performance extremes stand out, 3) isolated data points may accumulate to raise
      concern, and 4) developmental trajectory matters. The second domain focused on
      how CCC members and program directors interpret data to make decisions about
      residents with concerns and contained 2 themes: 1) using norm- and/or criterion
      referenced interpretation, and 2) assessing the quality of the data that is
      reviewed. CONCLUSIONS: Identifying residents with performance concerns is
      important for their education and the care they provide. This study delineates
      strategies used by CCC members across several programs for identifying these
      residents, which may be helpful for other CCCs to consider in their efforts.

PMID- 29345209
TI  - Medical Teacher in Ten Minutes.

PMID- 29345210
TI  - The impact of time from diagnosis to treatment in diffuse large B-cell lymphoma.
AB  - Diffuse large B-cell lymphoma (DLBCL) is a high-grade lymphoma that requires
      treatment. We retrospectively analyzed the impact of time from diagnosis-to
      treatment (TDT) on progression-free survival (PFS) and overall survival (OS) in
      581 R-CHOP-treated patients. TDT was defined as the interval between diagnostic
      biopsy date and day 1 R-CHOP. Cox regression showed stage 3-4 disease (p = .01)
      and longer TDT (HR 1.13, p =.031) were associated with shorter OS. Eastern
      Cooperative Oncology Group >=2 (p = .02), stage 3-4 disease (p < .001), and
      longer TDT (HR 1.12, p = .028) predicted shorter PFS. The significant
      interactions between TDT with lactate dehydrogenase (LDH) and with disease stage
      prompted separate analyses in high versus normal LDH, and stage 3-4 versus 1-2
      disease. Longer TDT was associated with shortened PFS and OS only with advanced
      stage, and, if high LDH was present. Treatment should be started as early as
      possible for high-tumor burden disease. Delaying treatment in patients with early
      stage or low LDH does not seem harmful.

PMID- 29345211
TI  - Developing single-entity theranostic: drug-based fluorescent nanoclusters with
      augmented cytotoxicity.
AB  - AIM: To develop methotrexate (MTX) templated luminescent gold nanoclusters (NCs)
      as a single unit nanotheranostic for cancer therapy and to assess its potential
      as an alternative to the parent drug, for drug delivery vehicles (DDVs). METHODS:
      Theranostics were synthesized and extensively characterized. The stability of the
      theranostic and its bioimaging aptitude were evaluated. The antiproliferative
      propensity of the theranostic was gauged with cell viability assays and was
      supplemented with cytometry-based assays. Feasibility of delivering the MTX NCs
      instead of parent drug on a DDV was also checked. RESULTS: MTX NCs displayed
      remarkable physical characteristics and augmented cytotoxicity with a robust
      stability in phosphate-buffered saline and serum. MTX NCs also demonstrated their
      amenability to being loaded on a DDV (chitosan folic acid nanoparticles) while
      retaining their physical and cytotoxic profile. CONCLUSION: Generation of next
      level drug-based theranostics with the potential of replacing the free drug in
      drug delivery platforms.

PMID- 29345212
TI  - Prioritising action to accelerate gender equity and health for women and girls:
      Microdata analysis of 47 countries.
AB  - The Sustainable Development Goals set ambitious targets for health. Meeting such
      will require drastic improvements in the social conditions for women and girls.
      Understanding which social conditions have the greatest impact on health can help
      prioritise action, yet there is little comparative data. We use microdata from
      338,580 women in 47 low- and middle-income countries to estimate the relative
      contributions of improved social determinants in bringing about maternal and
      child health gains over the past 20 years. Regression analyses examine
      determinants related to education, work, health services, family, and violence;
      the potential health benefit that could be derived from improving conditions is
      calculated. Secondary education and child marriage emerge as the strongest and
      most consistent predictors of health. The largest impact is seen on adolescent
      births: we estimate that achieving universal completion of secondary schooling
      for young women could lower adolescent births by 18 percentage points;
      eliminating child marriages could lower adolescent births by 11 points.
      Intervening in these two areas could also bring about substantial reductions in
      the unmet need for family planning, past-year intimate partner violence, and
      child mortality. Thus, we suggest prioritising policies targeting secondary
      education and child marriage in order to accelerate gender equity and health.

PMID- 29345213
TI  - Matcha Green Tea Drinks Enhance Fat Oxidation During Brisk Walking in Females.
AB  - Intake of the catechin epigallocatechin gallate and caffeine has been shown to
      enhance exercise-induced fat oxidation. Matcha green tea powder contains
      catechins and caffeine and is consumed as a drink. We examined the effect of
      Matcha green tea drinks on metabolic, physiological, and perceived intensity
      responses during brisk walking. A total of 13 females (age: 27 +/- 8 years, body
      mass: 65 +/- 7 kg, height: 166 +/- 6 cm) volunteered to participate in the study.
      Resting metabolic equivalent (1-MET) was measured using Douglas bags (1-MET: 3.4
      +/- 0.3 ml.kg-1.min-1). Participants completed an incremental walking protocol to
      establish the relationship between walking speed and oxygen uptake and
      individualize the walking speed at 5- or 6-MET. A randomized, crossover design
      was used with participants tested between Days 9 and 11 of the menstrual cycle
      (follicular phase). Participants consumed three drinks (each drink made with 1 g
      of Matcha premium grade; OMGTea Ltd., Brighton, UK) the day before and one drink
      2 hr before the 30-min walk at 5- (n = 10) or 6-MET (walking speed: 5.8 +/- 0.4
      km/hr) with responses measured at 8-10, 18-20, and 28-30 min. Matcha had no
      effect on physiological and perceived intensity responses. Matcha resulted in
      lower respiratory exchange ratio (control: 0.84 +/- 0.04; Matcha: 0.82 +/- 0.04;
      p < .01) and enhanced fat oxidation during a 30-min brisk walk (control: 0.31 +/-
      0.10; Matcha: 0.35 +/- 0.11 g/min; p < .01). Matcha green tea drinking can
      enhance exercise-induced fat oxidation in females. However, when regular brisk
      walking with 30-min bouts is being undertaken as part of a weight loss program,
      the metabolic effects of Matcha should not be overstated.

PMID- 29345214
TI  - Deciding to adopt revised and new psychological and neuropsychological tests: an
      inter-organizational position paper.
AB  - OBJECTIVE: Neuropsychological tests undergo periodic revision intended to improve
      psychometric properties, normative data, relevance of stimuli, and ease of
      administration. In addition, new tests are developed to evaluate psychological
      and neuropsychological constructs, often purporting to improve evaluation
      effectiveness. However, there is limited professional guidance to
      neuropsychologists concerning the decision to adopt a revised version of a test
      and/or replace an older test with a new test purporting to measure the same or
      overlapping constructs. This paper describes ethical and professional issues
      related to the selection and use of older versus newer psychological and
      neuropsychological tests, with the goal of promoting appropriate test selection
      and evidence-based decision making. METHOD: Ethical and professional issues were
      reviewed and considered. CONCLUSIONS: The availability of a newer version of a
      test does not necessarily render obsolete prior versions of the test for purposes
      that are empirically supported, nor should continued empirically supported use of
      a prior version of a test be considered unethical practice. Until a revised or
      new test has published evidence of improved ability to help clinicians to make
      diagnostic determinations, facilitate treatment, and/or assess change over time,
      the choice to delay adoption of revised or new tests may be viewed as reasonable
      and appropriate. Recommendations are offered to facilitate decisions about the
      adoption of revised and new tests. Ultimately, it is the responsibility of
      individual neuropsychologists to determine which tests best meet their patients'
      needs, and to be able to support their decisions with empirical evidence and
      sound clinical judgment.

PMID- 29345215
TI  - Relationship of "weekend warrior" and regular physical activity patterns with
      metabolic syndrome and its associated diseases among Chinese rural adults.
AB  - : Little is known about the "weekend warrior" pattern of physical activity (PA)
      where people perform all their PA in 1 or 2 sessions per week. We investigated
      the relationship of weekend warrior and other PA patterns with metabolic syndrome
      (MS) and its associated diseases. Data on sociodemographic and lifestyle
      characteristics were collected from the Nantong Metabolic Syndrome Study that
      included 13,505 women and 6,997 men between 2007 and 2008. Compared with inactive
      participants, weekend warriors were at lower risk of MS, diabetes, and
      hypertension; respective odds ratios (95% confidence intervals) for men and women
      were 0.58 (0.43-0.79) and 0.67 (0.52-0.86), 0.52 (0.34-0.79) and 0.52 (0.33
      0.83), and 0.79 (0.63-0.99) and 0.71 (0.57-0.89). Similar results were observed
      with regular activity, at a frequency of >3 sessions per week. Both weekend
      warrior and regular PA patterns showed a 10-60% decrease in abnormal
      triglycerides, glucose, and blood pressure in both sexes; abnormal waist
      circumference in men only; and abnormal high-density lipoprotein in women only.
      Our observed cross-sectional relationships reflect that >150 min/week of moderate
      PA or 75 min/week vigorous-intensity PA is needed to prevent MS and its component
      diseases, even if in a short-bout, intermittent PA pattern. ABBREVIATIONS: MS:
      Metabolic syndrome; WC: Waist circumference; TG: Triglycerides; HDL-c: High
      density lipoprotein cholesterol; BP: Blood pressure; SBP: Systolic blood
      pressure, DBP: Diastolic blood pressure; PA: Physical activity; JIS: Joint
      Interim Statement; CVD: Cardiovascular disease; ATP III: US Third Report of the
      National Cholesterol Education Program, the Adult Treatment Panel; IDF:
      International Diabetes Federation; IPAQ: International Physical Activity
      Questionnaire; BMI: Body mass index; CDC: the Nantong Centers for Disease
      Control; OR: Odds ratio; CI: Confidence interval; SD: Standard deviation; IQR:
      Interquartile range.

PMID- 29345216
TI  - A Novel System for Assessing Facial Muscle Movements: The Facegram 3D.

PMID- 29345217
TI  - Statistical analysis of human microarray data shows that dietary intervention
      with n-3 fatty acids, flavonoids and resveratrol enriches for immune response and
      disease pathways.
AB  - n-3 Fatty acids, flavonoids and resveratrol are well publicised for their
      beneficial effects on human health and wellbeing. Identifying common, underlying
      biological mechanisms targeted by these functional foods would therefore be
      informative for the public health sector for advising on nutritional health and
      disease, food and drug product development and consumer interest. The aim of this
      study was to explore the potential effects of gene expression changes associated
      with n-3 fatty acids EPA and DHA, flavonoids and resveratrol on modifying
      biological systems and disease pathways. To test this, publicly available human
      microarray data for significant gene expression changes associated with dietary
      intervention with EPA/DHA, flavonoids and resveratrol was subjected to pathway
      analysis and significance testing for overlap with signals from genome-wide
      association studies (GWAS) for common non-communicable diseases and biological
      functions. There was an enrichment of genes implicated in immune responses and
      disease pathways which was common to all of the treatment conditions tested.
      Analysis of biological functions and disease pathways indicated anti-tumorigenic
      properties for EPA/DHA. In line with this, significance testing of the
      intersection of genes associated with these functional foods and GWAS hits for
      common biological functions (ageing and cognition) and non-communicable diseases
      (breast cancer, CVD, diabesity, neurodegeneration and psychiatric disorders)
      identified significant overlap between the EPA/DHA and breast cancer gene sets.
      Dietary intervention with EPA/DHA, flavonoids and resveratrol can target
      important biological and disease pathways suggesting a potentially important role
      for these bioactive compounds in the prevention and treatment of dietary-related
      diseases.

PMID- 29345218
TI  - Mitochondrial DNA suggests cryptic speciation in Prodiplosis longifila Gagne
      (Diptera: Cecidomyiidae) associated with geographic distance and host
      specialization.
AB  - Prodiplosis longifila is reported as a pest of a wide range of species cultivated
      in America, including citrus, solanaceous species and asparagus. This species has
      different behavioural traits that are primarily centred on the oviposition habit
      and the feeding of larvae, which can change depending on the host. However,
      scarce information is available on population studies and the natural history of
      this insect, and uncertainty exists about the taxonomic identity and the
      geographic distribution of this species. The main objective was to perform a
      phylogenetic and genetic study of P. longifila populations and to define whether
      the North American and South American populations belong to the same species or
      whether a differentiation process had occurred due to geographic distance. A
      second objective was to determine whether this species showed genetic
      differentiation by host specialization in South America. The phylogenetic and
      population analyses based on DNA barcodes (cytochrome oxidase I gene) and a
      region of the ribosomal DNA (ITS2) revealed divergent clades attributable to
      geographic distance and host specificity. The North American and South American
      P. longifila insects were confirmed to be genetically distinct, and the genetic
      distances exceeded the values expected for intraspecific variation. In South
      America, the population analysis of P. longifila from tomato, sweet pepper
      (Solanaceae), Tahiti lime and key lime (Rutaceae) hosts evidenced high genetic
      differentiation between populations associated with different hosts and an
      absence of gene flow between these groups, suggesting the corresponding formation
      of cryptic species.

PMID- 29345219
TI  - Transcriptional changes when Myxococcus xanthus preys on Escherichia coli suggest
      myxobacterial predators are constitutively toxic but regulate their feeding.
AB  - Predation is a fundamental ecological process, but within most microbial
      ecosystems the molecular mechanisms of predation remain poorly understood. We
      investigated transcriptome changes associated with the predation of Escherichia
      coli by the myxobacterium Myxococcus xanthus using mRNA sequencing. Exposure to
      pre-killed prey significantly altered expression of 1319 predator genes. However,
      the transcriptional response to living prey was minimal, with only 12 genes being
      significantly up-regulated. The genes most induced by prey presence (kdpA and
      kdpB, members of the kdp regulon) were confirmed by reverse transcriptase
      quantitative PCR to be regulated by osmotic shock in M. xanthus, suggesting
      indirect sensing of prey. However, the prey showed extensive transcriptome
      changes when co-cultured with predator, with 40 % of its genes (1534) showing
      significant changes in expression. Bacteriolytic M. xanthus culture supernatant
      and secreted outer membrane vesicles (OMVs) also induced changes in expression of
      large numbers of prey genes (598 and 461, respectively). Five metabolic pathways
      were significantly enriched in prey genes up-regulated on exposure to OMVs,
      supernatant and/or predatory cells, including those for ribosome and
      lipopolysaccharide production, suggesting that the prey cell wall and protein
      production are primary targets of the predator's attack. Our data suggest a model
      of the myxobacterial predatome (genes and proteins associated with predation) in
      which the predator constitutively produces secretions which disable its prey
      whilst simultaneously generating a signal that prey is present. That signal then
      triggers a regulated feeding response in the predator.

PMID- 29345220
TI  - Tissue Impression Smears as a Supplementary Diagnostic Method for Histopathology
      in Cutaneous Leishmaniasis in Sri Lanka.
AB  - Cutaneous leishmaniasis (CL) is diagnosed mainly by light microscopy of smears
      made using lesion material. Histopathology is usually done in atypical
      presentations or when lesion smears are negative. Tissue impression smears (TIS)
      made from skin biopsy specimens were compared with histopathology for the
      diagnosis of CL. Out of the 111 patients included, 83 (74.8%) were positive by
      either methods. The TIS was positive in 70.3% whereas histopathology was positive
      in 56.8% of patients. Tissue impression smears can be used as a supplementary
      diagnostic test that gives sensitive and rapid results when tissue biopsies are
      used as the source of lesion material for diagnosis of CL.

PMID- 29345221
TI  - Therapeutic Response to Dihydroartemisinin-Piperaquine for P. falciparum and P.
      vivax Nine Years after Its Introduction in Southern Papua, Indonesia.
AB  - Dihydroartemisinin-piperaquine (DHP) has been the first-line treatment of
      uncomplicated malaria due to both Plasmodium falciparum and Plasmodium vivax
      infections in Papua, Indonesia, since March 2006. The efficacy of DHP was
      reassessed to determine whether there had been any decline following almost a
      decade of its extensive use. An open-label drug efficacy study of DHP for
      uncomplicated P. falciparum and P. vivax malaria was carried out between March
      2015 and April 2016 in Timika, Papua, Indonesia. Patients with uncomplicated
      malaria were administered supervised DHP tablets once daily for 3 days. Clinical
      and laboratory data were collected daily until parasite clearance and then weekly
      for 6 weeks. Molecular analysis was undertaken for all patients with recurrent
      parasitemia. A total of 129 study patients were enrolled in the study. At day 42,
      the polymerase chain reaction-adjusted efficacy was 97.7% (95% confidence
      intervals [CI]: 87.4-99.9) in the 61 patients with P. falciparum malaria, and
      98.2% [95% CI: 90.3-100] in the 56 patients with P. vivax malaria. By day 2, 98%
      (56/57) of patients with P. falciparum and 96.9% (63/65) of those with P. vivax
      had cleared their peripheral parasitemia; none of the patients were still
      parasitaemic on day 3. Molecular analysis of P. falciparum parasites showed that
      none (0/61) had K13 mutations associated previously with artemisinin resistance
      or increased copy number of plasmepsin 2-3 (0/61). In the absence of artemisinin
      resistance, DHP has retained high efficacy for the treatment of uncomplicated
      malaria despite extensive drug pressure over a 9-year period.

PMID- 29345222
TI  - Development and implementation of multilocus sequence typing to study the
      diversity of the yeast Kluyveromyces marxianus in Italian cheeses.
AB  - The yeast Kluyveromyces marxianus possesses advantageous traits like rapid
      growth, GRAS (generally regarded as safe) status and thermotolerance that make it
      very suitable for diverse biotechnological applications. Although physiological
      studies demonstrate wide phenotypic variation within the species, there is only
      limited information available on the genetic diversity of K. marxianus. The aim
      of this work was to develop a multilocus sequence typing (MLST) method for K.
      marxianus to improve strain classification and selection. Analysis of
      housekeeping genes in a number of sequenced strains led to the selection of five
      genes, IPP1, TFC1, GPH1, GSY2 and SGA1, with sufficient polymorphic sites to
      allow MLST analysis. These loci were sequenced in an additional 76 strains and
      used to develop the MLST. This revealed wide diversity in the species and
      separation of the culture collection and wild strains into multiple distinct
      clades. Two subsets of strains that shared sources of origin were subjected to
      MLST and split decomposition analysis. The latter revealed evidence of
      recombination, indicating that this yeast undergoes mating in the wild. A public
      access web-based portal was established to allow expansion of the database and
      application of MLST to additional K. marxianus strains. This will aid
      understanding of the genetic diversity of the yeast and facilitate
      biotechnological exploitation.

PMID- 29345224
TI  - Therapy interventions for children with neurodisabilities: a qualitative scoping
      study.
AB  - BACKGROUND: Therapy interventions emerged four times in the top 10 research
      priorities in a James Lind Alliance research prioritisation exercise for children
      with neurodisabilities (Morris C, Simkiss D, Busk M, Morris M, Allard A, Denness
      J, et al. Setting research priorities to improve the health of children and young
      people with neurodisability: a British Academy of Childhood Disability-James Lind
      Alliance Research Priority Setting Partnership. BMJ Open 2015;5:e006233). The
      National Institute for Health Research (NIHR) commissioned this study as part of
      an information-gathering exercise in response to this. OBJECTIVES: The objectives
      were to (1) describe the current practice, approaches and schools of thought in
      relation to physiotherapy, occupational therapy and speech and language therapy
      for children with neurodisability; (2) explore clinical decision-making; (3)
      investigate views on outcomes and their measurement, particularly participation
      as an outcome, that is, the child's ability to have the opportunity to be
      involved in life situations and activities (e.g. communication, mobility,
      interpersonal interactions, self-care, learning and applying knowledge); (4) seek
      views on the aspects of therapy interventions that have an impact on outcomes;
      and (5) elicit stakeholder views on research needs and priorities. DESIGN,
      SETTING AND PARTICIPANTS: More than 70 professionals (therapists, service leads,
      paediatricians and education staff) and 25 parents participated in a qualitative
      interview (either individually or as part of a focus group). RESULTS:
      Professional thinking and models of service delivery are in a state of flux and
      development. There is a move towards goals-focused, family-centred approaches.
      Work tends to be highly individualised, with few protocols. Parents are certain
      of the value of therapies, although they may experience difficulties with
      provision and may seek (additional) private provision. Therapy interventions are
      conceived as three components: the therapist, the procedures/equipment, etc., and
      the wider therapeutic environment. They are believed to be highly complex and
      poorly understood. Although participation is widely endorsed as a core
      intervention objective of therapy interventions, its suitability, or
      appropriateness, as an outcome measure was questioned. Other child and/or parent
      outcomes were identified as more or equally important. Notions of intermediate
      outcomes - in terms of body structure/function, and the achievement of activities
      - were regarded as important and not counter to participation-focused approaches.
      Among therapists, research on intervention effectiveness was (cautiously)
      welcomed. A number of methodological challenges were identified. A portfolio of
      study designs - quantitative and qualitative, experimental and observational -
      was called for, and which included economic evaluation and clear pathways to
      impact. LIMITATIONS: The study was not successful in recruiting children and
      young people. Further work is required to elucidate the views of this key
      stakeholder group. CONCLUSIONS: Therapy interventions are poorly understood.
      There was strong support, tempered a little by concerns among some about the
      feasibility of demonstrating impact, for investment in research. FUTURE WORK: The
      identification of research priorities was a core study objective, and a wide
      ranging research agenda was identified. It included 'foundational' research into
      neurodisability, the active components of therapy interventions and the concept
      of participation. Three areas of evaluation were identified: overall approaches
      to therapy, service organisation and delivery issues, and the evaluation of
      specific techniques. Parents regarded evaluations of approaches to therapy (e.g.
      goals-focused; supporting family-self management) as priorities, along with
      evaluations of models of service provision. Professionals' views were broadly
      similar, with an additional emphasis on methodological research. In terms of
      specific techniques, there was no shared agreement regarding priorities, with
      views informed by personal interests and experiences. FUNDING: The NIHR Health
      Technology Assessment programme.

PMID- 29345223
TI  - Case Report: Neurobrucellosis with Plastered Spinal Arachnoiditis: A Magnetic
      Resonance Imaging-Based Report.
AB  - Diffuse spinal arachnoiditis in neurobrucellosis is a rare manifestation. We
      report a boy aged 17, presenting with hearing impairment and recurrent vomiting
      for 18 months, weight loss for 12 months, dysphagia, dysarthria, hypophonia for 6
      months, and gait unsteadiness for 5 months. He had bilateral 5th (motor) to 12th
      cranial nerve palsy, wasting and weakness of limbs, fasciculations, absent tendon
      reflexes, and positive Babinski's sign. Cerebrospinal fluid (CSF) showed raised
      protein and pleocytosis. Magnetic resonance imaging (MRI) showed extensive
      enhancing exudates in cisterns and post-contrast enhancement of bilateral 5th,
      6th, 7th, and 8th nerves. Spine showed clumping with contrast enhancement of the
      cauda equina roots and encasement of the cord with exudates. Serum and CSF were
      positive for anti-Brucella antibodies. He showed significant improvement with
      antibiotics. At 4 months follow-up, MRI demonstrated near complete resolution of
      cranial and spinal arachnoiditis. It is important to recognize such rare atypical
      presentations of neurobrucellosis.

PMID- 29345226
TI  - Failure to Use Ultrasound Is a Glaring Shortcoming.

PMID- 29345225
TI  - Indications for the Surgical Management of Benign Goiter in Adults.
AB  - BACKGROUND: Thyroidectomy is still three to six times more common in Germany than
      in the USA, Great Britain, and the Scandinavian countries. Thus, the question is
      often asked whether thyroidectomy in Germany is being performed for the correct
      indications. METHODS: This review is based on studies and guidelines containing
      information on the indications for surgery in benign goiter and Graves' disease;
      these publications were retrieved by a systematic literature search in the
      Medline and Cochrane Library databases (1990-2016). The indications recommended
      here were determined by vote by the German Society for General and Visceral
      Surgery (Deutsche Gesellschaft fur Allgemein- und Viszeralchirurgie, DGAV).
      RESULTS: On the basis of the available evidence (levels 2-4), and in the absence
      of prospective studies, the indications for surgery in goiter include a well
      founded suspicion of malignancy, local compressive symptoms, and, rarely,
      cosmesis. In hyperthyroid goiter and Graves' disease, surgery is a potential
      alternative to radio - iodine therapy, particularly if the volume of the thyroid
      gland exceeds 80 mL, in patients with advanced or active orbitopathy, and in
      female patients who are, or plan to be, pregnant. Large, asymptomatic, euthyroid
      nodular goiter without any suspicion of malignancy and scintigraphically "cold"
      nodules without any other evidence of malignancy are not indications for surgery.
      Thyroid operations of higher levels of difficulty (e.g., recurrent goiter,
      retrosternal extension, Graves' disease) should be carried out in institutions
      with special expertise in thyroid surgery. CONCLUSION: The decision to operate
      should be made on an interdisciplinary basis and in conformity with the relevant
      guidelines after all of the appropriate diagnostic studies have been performed.
      The radicality of any proposed surgical procedure should be weighed against its
      potential complications.

PMID- 29345227
TI  - Experience and a Certain Amount of Time Are Required.

PMID- 29345228
TI  - Ultrasound First.

PMID- 29345229
TI  - Oral Contrast is no Longer Needed.

PMID- 29345230
TI  - Critical Scrutiny Needed.

PMID- 29345231
TI  - In Reply.

PMID- 29345232
TI  - A Rare Cause of Chronic Cough.

PMID- 29345233
TI  - Multiple Endobronchial Chondromas.

PMID- 29345235
TI  - News on Climate Change, Air Pollution, and Allergic Triggers of Asthma.
AB  - The rising frequency of obstructive respiratory diseases during recent years, in
      particular allergic asthma, can be partially explained by changes in the
      environment, with the increasing presence in the atmosphere of chemical triggers
      (particulate matter and gaseous components such as nitrogen dioxide and ozone)
      and biologic triggers (aeroallergens). In allergic individuals, aeroallergens
      stimulate airway sensitization and thus induce symptoms of bronchial asthma. Over
      the last 50 years, the earth's temperature has risen markedly, likely because of
      growing concentrations of anthropogenic greenhouse gas. Major atmospheric and
      climatic changes, including global warming induced by human activity, have a
      considerable impact on the biosphere and on the human environment. Urbanization
      and high levels of vehicle emissions induce symptoms of bronchial obstruction (in
      particular bronchial asthma), more so in people living in urban areas compared
      than in those who live in rural areas. Measures need to be taken to mitigate the
      future impact of climate change and global warming. However, while global
      emissions continue to rise, we must learn to adapt to climate variability.

PMID- 29345234
TI  - Current Approaches to Epistaxis Treatment in Primary and Secondary Care.
AB  - BACKGROUND: The lifetime prevalence of epistaxis is approximately 60%, and 6-10%
      of the affected persons need medical care. In rare cases, severe bleeding calls
      for the rapid initiation of effective treatment. METHODS: This review is based on
      pertinent articles that were retrieved by a selective search PubMed, and on the
      authors' clinical experience. RESULTS: There are no German guidelines for the
      management of epistaxis. The available evidence consists mainly of retro spective
      analyses and expert opinions. 65-75% of the patients who require treatment can be
      adequately cared for by their primary care physician or by an emergency physician
      with baseline measures. If there is persistent anterior epistaxis, an
      otorhinolaryngologist can control the bleeding sastisfactorily in 78-88% of cases
      with chemical or electrical cauterization. Nasal packing is used if this
      treatment fails, or for posterior epistaxis. In a retrospective study, surgical
      treatment was found to be more effective than nasal packing in the treatment of
      posterior epistaxis (97% versus 62% treatment success). Percutaneous embolization
      is an alternative treatment for patients whom general anesthesia would put at
      high risk. CONCLUSION: The treatment of severe or recurrent epistaxis requires
      the interdisciplinary collaboration of the primary care physician, the emergency
      physician, the practice-based otolaryngologist, and the hospital otolaryngology
      service. Uniform guidelines and epidemiological studies on this topic would be
      desirable.

PMID- 29345237
TI  - Beyond the impact factor: may we have your attention, please?

PMID- 29345236
TI  - GLCCI1 Polymorphism rs37973 and Response to Treatment of Asthma With Inhaled
      Corticosteroids.
AB  - BACKGROUND: The response to asthma treatment is highly variable, and having
      pharmacogenetic markers that predict response to treatment would bring us one
      step closer to personalized treatment. Genome-wide association studies have shown
      that polymorphisms in GLCCI1 could be associated with the response to inhaled
      corticosteroids (ICSs) in asthma patients. MATERIAL AND METHODS: We genotyped
      rs37973 in GLCCI1 in 208 adult asthma patients treated with ICSs. The percentage
      change in FEV1, % predicted was analyzed after short-term treatment (3 months)
      and long-term treatment (at least 3 years). Treatment was defined as successful
      when FEV1 decreased by <30 mL/year. RESULTS: After 3 months of treatment, FEV1, %
      predicted was higher in patients with the GG genotype than in patients with the
      AG+AA genotype, and this genotype-dependent difference was only evident in
      nonsmokers. Similar results were found in nonsmokers and patients with atopy
      after at least 3 years of treatment, when all patients were analyzed. Even though
      no differences were observed for success of treatment (good vs poor response)
      when the whole group of patients was analyzed, genotype-dependent treatment
      success was highly influenced by smoking and atopy. The GG genotype was
      overrepresented in nonsmokers and patients with atopy and a good response.
      CONCLUSIONS: rs37973 was associated with response to short- and long-term
      treatment; however, smoking and atopy had a considerable effect on
      pharmacogenetic association. Furthermore, in contrast with findings from genome
      wide association studies, we found the GG genotype to be associated with better
      treatment response.

PMID- 29345238
TI  - Assessing coronary disease in patients with severe aortic stenosis: the need for
      a 'valid' gold standard for validation studies?

PMID- 29345239
TI  - The business of risk.

PMID- 29345240
TI  - Polymeric bioresorbable coronary scaffolds: the hype is over, but the dream lives
      on.

PMID- 29345242
TI  - Joint estimation of activity and attenuation for PET using pragmatic MR-based
      prior: application to clinical TOF PET/MR whole-body data for FDG and non-FDG
      tracers.
AB  - Accurate and robust attenuation correction remains challenging in hybrid PET/MR
      particularly for torsos because it is difficult to segment bones, lungs and
      internal air in MR images. Additionally, MR suffers from susceptibility artifacts
      when a metallic implant is present. Recently, joint estimation (JE) of activity
      and attenuation based on PET data, also known as maximum likelihood
      reconstruction of activity and attenuation, has gained considerable interest
      because of (1) its promise to address the challenges in MR-based attenuation
      correction (MRAC), and (2) recent advances in time-of-flight (TOF) technology,
      which is known to be the key to the success of JE. In this paper, we implement a
      JE algorithm using an MR-based prior and evaluate the algorithm using whole-body
      PET/MR patient data, for both FDG and non-FDG tracers, acquired from GE SIGNA
      PET/MR scanners with TOF capability. The weight of the MR-based prior is
      spatially modulated, based on MR signal strength, to control the balance between
      MRAC and JE. Large prior weights are used in strong MR signal regions such as
      soft tissue and fat (i.e. MR tissue classification with a high degree of
      certainty) and small weights are used in low MR signal regions (i.e. MR tissue
      classification with a low degree of certainty). The MR-based prior is pragmatic
      in the sense that it is convex and does not require training or population
      statistics while exploiting synergies between MRAC and JE. We demonstrate the JE
      algorithm has the potential to improve the robustness and accuracy of MRAC by
      recovering the attenuation of metallic implants, internal air and some bones and
      by better delineating lung boundaries, not only for FDG but also for more
      specific non-FDG tracers such as 68Ga-DOTATOC and 18F-Fluoride.

PMID- 29345243
TI  - Electronic and mechanical response of graphene on BaTiO3 at martensitic phase
      transitions.
AB  - Graphene is extremely sensitive to optical, electrical and mechanical stimuli,
      which cause a significant variation of the band structure, thus the
      physiochemical properties. In our work, we report on changes of strain and doping
      in graphene grown by chemical vapor deposition on copper and transferred onto a
      BaTiO3(1 0 0) (BTO) single-crystal. The BTO is known as a ferroelectric material,
      which undergoes several thermoelastic martensitic phase transitions when it is
      cooled from 300 K to 10 K. In order to enhance the very weak Raman signal of the
      graphene monolayer (ML) on the BTO, a 15 nm thin gold layer was deposited on top
      of the graphene ML to benefit from the surface enhanced Raman scattering. Using
      temperature dependent Raman spectral mapping, the principal Raman modes (D, G and
      2D) of the graphene ML were followed in situ. From a careful analysis of these
      Raman modes, we conclude that the induced strain and doping of the graphene ML
      follows the martensitic phase transitions of the BTO crystal. Our study suggests
      potential exploitation of the graphene as a highly sensitive opto-mechanical
      sensor or transducer.

PMID- 29345244
TI  - In vitro physical and biological characterization of biodegradable elastic
      polyurethane containing ferulic acid for small-caliber vascular grafts.
AB  - Demand for small diameter vascular grafts is growing. The main limitations of
      these grafts include induced thrombotic events, lack of in situ
      endothelialization, intimal hyperplasia and poor mechanical properties which
      impair the graft patency rate in long-term applications. Most anti-thrombotic
      modification methods currently in use usually conflict with the formation of an
      endothelial cell monolayer on the grafts. Here, we synthesized a novel
      biodegradable poly(ether ester urethane)urea elastomer (PEEUU) using
      poly(ethylene glycol) and poly(diethylene glycol adipate) as soft segments. To
      improve hemocompatibility, synthesized PEEUU was blended with ferulic acid (FA).
      Scanning electron microscopy, water contact angle measurement, and tensile
      testing were used to characterize the scaffolds. The PEEUU and PEEUU-FA scaffolds
      revealed appropriate mechanical properties, with tensile strengths and strains
      similar to a coronary artery. In vitro assay demonstrated that the release of FA
      from the scaffold is in a sustained manner. Hemocompatibility tests indicated
      that the PEEUU-FA sample induced lower platelet adhesion compared to the PEEUU
      sample. Reductions in hemolysis and fibrinogen adsorption were detected on the
      PEEUU-FA sample. Cell studies showed that PEEUU-FA supported the adhesion,
      expansion and proliferation of endothelial cells. The cells maintained an
      endothelial cell phenotype through the expression of the endothelial cell marker
      CD31. The results revealed that the new PEEUU modified with FA can be considered
      as a promising candidate for vascular applications with enhanced blood
      compatibility and vascular cell-compatibility.

PMID- 29345245
TI  - Isolating long-wavelength fluctuation from structural relaxation in two
      dimensional glass: cage-relative displacement.
AB  - It has recently been revealed that long-wavelength fluctuation exists in two
      dimensional (2D) glassy systems, having the same origin as that given by the
      Mermin-Wagner theorem for 2D crystalline solids. In this paper, we discuss how to
      characterise quantitatively the long-wavelength fluctuation in a molecular
      dynamics simulation of a lightly supercooled liquid. We employ the cage-relative
      mean-square displacement (MSD), defined on relative displacement to its cage, to
      quantitatively separate the long-wavelength fluctuation from the original MSD.
      For increasing system size the amplitude of acoustic long wavelength fluctuations
      not only increases but shifts to later times causing a crossover with structural
      relaxation of caging particles. We further analyse the dynamic correlation length
      using the cage-relative quantities. It grows as the structural relaxation becomes
      slower with decreasing temperature, uncovering an overestimation by the four
      point correlation function due to the long-wavelength fluctuation. These findings
      motivate the usage of cage-relative MSD as a starting point for analysis of 2D
      glassy dynamics.

PMID- 29345246
TI  - Graphene-based stretchable and transparent moisture barrier.
AB  - We propose an alumina-deposited double-layer graphene (2LG) as a transparent,
      scalable, and stretchable barrier against moisture; this barrier is indispensable
      for foldable or stretchable organic displays and electronics. Both the barrier
      property and stretchability were significantly enhanced through the introduction
      of 2LG between alumina and a polymeric substrate. 2LG with negligible polymeric
      residues was coated on the polymeric substrate via a scalable dry transfer method
      in a roll-to-roll manner; an alumina layer was deposited on the graphene via
      atomic layer deposition. The effect of the graphene layer on crack generation in
      the alumina layer was systematically studied under external strain using an in
      situ micro-tensile tester, and correlations between the deformation-induced
      defects and water vapor transmission rate were quantitatively analyzed. The
      enhanced stretchability of alumina-deposited 2LG originated from the interlayer
      sliding between the graphene layers, which resulted in the crack density of the
      alumina layer being reduced under external strain.

PMID- 29345247
TI  - Calculation of the exposure buildup factors for x-ray photons with continuous
      energy spectrum using Monte Carlo code.
AB  - Exposure buildup factors are very important for the calculation of radiation
      shielding and also applied radiation. We must distinguish the monoenergetic and
      continuous energy spectrum gamma source in order to calculate the exposure
      buildup factors. In this study, the exposure buildup factors for two x-ray
      continuous energy spectra (bremsstrahlung) with 5 and 10 MeV endpoint energies
      were calculated up to depths of 10 mfp of water. It was observed that there is a
      large difference between the obtained exposure buildup factors due to the
      monoenergetic and continuous energy spectrum gamma sources. The calculation
      results show that the relative differences in 5 MeV energy for 1 mfp to 10 mfp
      are 114% to 44%, respectively, and also the relative differences in 10 MeV energy
      for 1 mfp to 10 mfp are 87% to 38%, respectively. Actually, the main purpose of
      this paper is to illustrate the fact that there is a significant difference
      between the exposure buildup factors due to the continuous and monoenergetic
      gamma sources. Therefore, radiation staff must pay more attention to calculating
      the thickness of radiation shields for continuous energy gamma sources.

PMID- 29345248
TI  - Photo-assisted hysteresis of electronic transport for ZnO nanowire transistors.
AB  - Recently, ZnO nanowire field effect transistors (FETs) have received renewed
      interest due to their extraordinary low dimensionality and high sensitivity to
      external chemical environments and illumination conditions. These prominent
      properties have promising potential in nanoscale chemical and photo-sensors. In
      this article, we have fabricated ZnO nanowire FETs and have found hysteresis
      behavior in their transfer characteristics. The mechanism and dynamics of the
      hysteresis phenomena have been investigated in detail by varying the sweeping
      rate and range of the gate bias with and without light irradiation.
      Significantly, light irradiation is of great importance on charge trapping by
      regulating adsorption and desorption of oxygen at the interface of ZnO/SiO2.
      Carriers excited by light irradiation can dramatically promote
      trapping/detrapping processes. With the assistance of light illumination, we have
      demonstrated a photon-assisted nonvolatile memory which employs the ZnO nanowire
      FET. The device exhibits reliable programming/erasing operations and a large
      on/off ratio. The proposed proto-type memory has thus provided a possible novel
      path for creating a memory functionality to other low-dimensional material
      systems.

PMID- 29345250
TI  - Cancer-associated cachexia.

PMID- 29345249
TI  - Effects of 1,25-Dihydroxyvitamin D3 on the Prevention of Chronic Obstructive
      Pulmonary Disease (COPD) in Rats Exposed to Air Pollutant Particles Less than 2.5
      Micrometers in Diameter (PM2.5).
AB  - BACKGROUND This study aimed to investigate the effects of 1,25-dihydroxyvitamin
      D3 (1,25(OH)2D3) on airway changes in chronic obstructive pulmonary disease
      (COPD) rats exposed to air pollutant particles less than 2.5 micrometers in
      diameter (PM2.5), and to evaluate the mechanisms. MATERIAL AND METHODS Three
      groups were included in this study: a normal group, a COPD model group, and a
      COPD with 1,25(OH)2D3 treatment group. In each group, the rats were divided into
      four subgroups: control and different doses of PM2.5 (1.6, 8 and 40 mg/kg body
      weight). Apoptosis in lung tissue was detected by terminal deoxynucleotidyl
      transferase dUTP nick end labeling (TUNEL). The expression of c-Jun N-terminal
      kinase 1 (JNK1) and mucin 5AC (MUC5AC) were detected by real-time polymerase
      chain reaction (RT-PCR), Western blotting and immunofluorescence staining.
      RESULTS Compared with corresponding subgroups in normal group, the apoptotic
      rates in COPD group were significantly increased. By contrast, 1,25(OH)2D3
      treatment group significantly reduced COPD-induced apoptosis in lung tissue. Upon
      the dose increase of PM2.5, the apoptotic rate was also elevated in each group.
      Compared with the corresponding control in each group, PM2.5 increased apoptosis
      in a dose-dependent manner. Importantly, 1,25(OH)2D3 also prevented apoptosis in
      COPD rats exposed to PM2.5. Mechanically, the expression of MUC5AC and JNK1 in
      COPD group was significantly upregulated, compared with corresponding subgroups
      in the normal group. Treatment with 1,25(OH)2D3 reduced expression of MUC5AC and
      JNK1 in COPD rats. It was found that the expression of MUC5AC and JNK1 was
      elevated with the dose increase of PM2.5 in each group. Consistently, 1,25(OH)2D3
      also reduced the expression of MUC5AC and JNK1 in COPD rats exposed to PM2.5.
      CONCLUSIONS 1,25(OH)2D3 prevented lung injury in COPD rats with or without PM2.5
      exposure. Our results suggest that 1,25(OH)2D3 is useful to mitigate the injury
      caused by COPD.

PMID- 29345251
TI  - Cancer-associated cachexia.
AB  - Cancer-associated cachexia is a disorder characterized by loss of body weight
      with specific losses of skeletal muscle and adipose tissue. Cachexia is driven by
      a variable combination of reduced food intake and metabolic changes, including
      elevated energy expenditure, excess catabolism and inflammation. Cachexia is
      highly associated with cancers of the pancreas, oesophagus, stomach, lung, liver
      and bowel; this group of malignancies is responsible for half of all cancer
      deaths worldwide. Cachexia involves diverse mediators derived from the cancer
      cells and cells within the tumour microenvironment, including inflammatory and
      immune cells. In addition, endocrine, metabolic and central nervous system
      perturbations combine with these mediators to elicit catabolic changes in
      skeletal and cardiac muscle and adipose tissue. At the tissue level, mechanisms
      include activation of inflammation, proteolysis, autophagy and lipolysis.
      Cachexia associates with a multitude of morbidities encompassing functional,
      metabolic and immune disorders as well as aggravated toxicity and complications
      of cancer therapy. Patients experience impaired quality of life, reduced
      physical, emotional and social well-being and increased use of healthcare
      resources. To date, no effective medical intervention completely reverses
      cachexia and there are no approved drug therapies. Adequate nutritional support
      remains a mainstay of cachexia therapy, whereas drugs that target overactivation
      of catabolic processes, cell injury and inflammation are currently under
      investigation.

PMID- 29345253
TI  - 3-Acetyl-oleanolic acid ameliorates non-alcoholic fatty liver disease in high fat
      diet-treated rats by activating AMPK-related pathways.
AB  - 3-Acetyl-oleanolic acid (3Ac-OA) is a derivative of oleanolic acid (OA), which
      has shown therapeutic beneficial effects on diabetes and metabolic syndrome. In
      this study we investigated whether 3Ac-OA exerted beneficial effect on non
      alcoholic fatty liver disease (NAFLD) in rats and its potential underlying
      mechanisms. Treatment with 3Ac-OA (1-100 MUmol/L) dose-dependently decreased the
      intracellular levels of total cholesterol (TC) and triglyceride (TG) in FFA
      treated primary rat hepatocytes and human HepG2 cell lines in vitro. Furthermore,
      oil red staining studies showed that 3Ac-OA caused dose-dependent decrease in the
      number of lipid droplets in FFA-treated primary rat hepatocytes. SD rats were fed
      a high fat diet (HFD) for 6 weeks and subsequently treated with 3Ac-OA (60, 30,
      15 mg.kg-1.d-1) for 4 weeks. 3Ac-OA administration significantly decreased the
      body weight, liver weight and serum TC, TG, LDL-C levels in HFD rats.
      Furthermore, 3AcOA administration ameliorated lipid accumulation and cell
      apoptosis in the liver of HFD rats. Using adipokine array analyses, we found that
      the levels of 11 adipokines (HGF, ICAM, IGF-1, IGFBP-3, IGFBP-5, IGFBP-6,
      lipocalin-2, MCP-1, M-CSF, Pref-1 and RAGE) were increased by more than twofold
      in the serum of 3Ac-OA-treated rats, whereas ICAM, IGF-1 and lipocalin-2 had
      levels increased by more than 20-fold. Moreover, 3Ac-OA administration
      significantly increased the expression of glucose transporter type 2 (GLUT-2) and
      low-density lipoprotein receptor (LDLR), as well as the phosphorylation of AMP
      activated protein kinase (AMPK), protein kinase B (AKT) and glycogen synthase
      kinase 3beta (GSK-3beta) in the liver tissues of HFD rats. In conclusion, this
      study demonstrates that 3Ac-OA exerts a protective effect against hyperlipidemia
      in NAFLD rats through AMPK-related pathways.

PMID- 29345252
TI  - Optimization of lentiviral vector production for scale-up in fixed-bed
      bioreactor.
AB  - Lentiviral vectors (LVs) are promising tools for gene therapy. However, scaling
      up the production methods of LVs in order to produce high-quality vectors for
      clinical purposes has proven to be difficult. In this article, we present a
      scalable and efficient method to produce LVs with transient transfection of
      adherent 293T cells in a fixed-bed bioreactor. The disposable iCELLis bioreactors
      are scalable with a large three-dimensional (3D) growth area range between 0.53
      and 500 m2, an integrated perfusion system, and a controllable environment for
      production. In this study, iCELLis Nano (2.67-4 m2) was used for optimizing
      production parameters for scale-up. Transfections were first done using
      traditional calcium phosphate method, but in later runs polyethylenimine was
      found to be more reliable and easier to use. For scalable LV production,
      perfusion rate control by measuring cell metabolite concentrations in the
      bioreactor leads to higher productivity and reduced costs. Optimization of cell
      seeding density for targeted cell concentration during transfection, use of low
      compaction fixed-bed and lowering the culture pH have a positive effect on LV
      productivity. These results show for the first time that iCELLis bioreactor is
      scalable from bench level to clinical scale LV production.

PMID- 29345254
TI  - The mTOR inhibitor AZD8055 overcomes tamoxifen resistance in breast cancer cells
      by down-regulating HSPB8.
AB  - Tamoxifen, an important endocrine therapeutic agent, is widely used for the
      treatment of estrogen receptor positive (ER+) breast cancer. However, de novo or
      acquired resistance prevents patients from benefitting from endocrine approaches
      and necessitates alternative treatments. In this study, we report that small heat
      protein beta-8 (HSPB8) may serve as an important molecule in tamoxifen
      resistance. HSPB8 expression is enhanced in MCF-7 cells resistant to tamoxifen
      (MCF-7/R) compared to parent cells. Moreover, high expression of HSPB8 associates
      with poor prognosis in ER+ breast cancer patients but not in patients without
      classification. Stimulating ER signaling by heterogeneous expression of ERa or
      17beta-estradiol promotes HSPB8 expression and reduces the cell population in G1
      phase. In contrast, blockage of ER signaling by tamoxifen down-regulates the
      expression of HSPB8. In addition, knocking down HSPB8 by specific siRNAs induces
      significant cell cycle arrest at G1 phase. AZD8055 was found to be more potent
      against the proliferation of MCF-7/R cells than that of parent cells, which was
      associated with down-regulation of HSPB8. We found that the anti-proliferative
      activity of AZD8055 was positively correlated with the HSPB8 expression level in
      ER+ breast cancer cells. Thus, AZD8055 was able to overcome tamoxifen resistance
      in breast cancer cells, and the expression of HSPB8 may predict the efficacy of
      AZD8055 in ER+ breast cancer. This hypothesis deserves further investigation.

PMID- 29345256
TI  - Caregiver Perspectives on Communication During Hospitalization at an Academic
      Pediatric Institution: A Qualitative Study.
AB  - OBJECTIVE: Communication among those involved in a child's care during
      hospitalization can mitigate or exacerbate family stress and confusion. As part
      of a broader qualitative study, we present an in-depth understanding of
      communication issues experienced by families during their child's hospitalization
      and during the transition to home. METHODS: Focus groups and individual
      interviews stratified by socioeconomic status included caregivers of children
      recently discharged from a children's hospital after acute illnesses. An open
      ended, semistructured question guide designed by investigators included
      communication-related questions addressing information shared with families from
      the medical team about discharge, diagnoses, instructions, and care plans. By
      using an inductive thematic analysis, 4 investigators coded transcripts and
      resolved differences through consensus. RESULTS: A total of 61 caregivers across
      11 focus groups and 4 individual interviews participated. Participants were 87%
      female and 46% non-white. Analyses resulted in 3 communication-related themes.
      The first theme detailed experiences affecting caregiver perceptions of
      communication between the inpatient medical team and families. The second
      revealed communication challenges related to the teaching hospital environment,
      including confusing messages associated with large multidisciplinary teams,
      aspects of family-centered rounds, and confusion about medical team member roles.
      The third reflected caregivers' perceptions of communication between providers in
      and out of the hospital, including types of communication caregivers observed or
      believed occurred between medical providers. CONCLUSIONS: Participating
      caregivers identified various communication concerns and challenges during their
      child's hospitalization and transition home. Caregiver perspectives can inform
      strategies to improve experiences, ease challenges inherent to a teaching
      hospital, and determine which types of communication are most effective.

PMID- 29345257
TI  - Engaging Families as True Partners During Hospitalization.

PMID- 29345255
TI  - Pure mechanistic analysis of additive neuroprotective effects between baicalin
      and jasminoidin in ischemic stroke mice.
AB  - Both baicalin (BA) and jasminoidin (JA) are active ingredients in Chinese herb
      medicine Scutellaria baicalensis and Fructus gardeniae, respectively. They have
      been shown to exert additive neuroprotective action in ischemic stroke models. In
      this study we used transcriptome analysis to explore the pure therapeutic
      mechanisms of BA, JA and their combination (BJ) contributing to phenotype
      variation and reversal of pathological processes. Mice with middle cerebral
      artery obstruction were treated with BA, JA, their combination (BJ), or concha
      margaritifera (CM). Cerebral infarct volume was examined to determine the effect
      of these compounds on phenotype. Using the hippocampus microarray and ingenuity
      pathway analysis (IPA) software, we exacted the differentially expressed genes,
      networks, pathways, and functions in positive-phenotype groups (BA, JA and BJ) by
      comparing with the negative-phenotype group (CM). In the BA, JA, and BJ groups, a
      total of 7, 4, and 11 specific target molecules, 1, 1, and 4 networks, 51, 59,
      and 18 canonical pathways and 70, 53, and 64 biological functions, respectively,
      were identified. Pure therapeutic mechanisms of BA and JA were mainly overlapped
      in specific target molecules, functions and pathways, which were related to the
      nervous system, inflammation and immune response. The specific mechanisms of BA
      and JA were associated with apoptosis and cancer-related signaling and endocrine
      and hormone regulation, respectively. In the BJ group, novel target profiles
      distinct from mono-therapies were revealed, including 11 specific target
      molecules, 10 functions, and 10 pathways, the majority of which were related to a
      virus-mediated immune response. The pure additive effects between BA and JA were
      based on enhanced action in virus-mediated immune response. This pure mechanistic
      analysis may provide a clearer outline of the target profiles of multi-target
      compounds and combination therapies.

PMID- 29345258
TI  - Combination of a graphene SERS substrate and magnetic solid phase micro
      extraction used for the rapid detection of trace illegal additives.
AB  - Surface enhanced Raman scattering (SERS) is an ultra-sensitive spectroscopy
      technique, which can provide rich structural information for a great number of
      molecules, while solid phase micro-extraction (SPME) is an efficient method for
      sample pretreatment in analytical chemistry, particularly in a micro-system. In
      the present report, a silver-loaded and graphene-based magnetic composite
      (Fe3O4@GO@Ag) was fabricated for use as both a SERS-active substrate and SPME
      material. The pi-pi stacking and fluorescence quenching abilities of GO make the
      composite a perfect candidate for SERS in analyzing real-world samples.
      Therefore, through combining the magnetic nanoparticles with a SPME device, we
      have developed a pretreatment method named as disperse magnetic solid phase micro
      extraction (Dis-MSPME). In comparison to traditional SPME, the proposed Dis-MSPME
      realized solid phase micro-extraction from a dispersive system and largely
      improved the extraction efficiency. Furthermore, by combining the advantages of
      both Dis-MSPME and SERS we have proposed a new detection method called Dis-MSPME
      SERS. Finally, as an example, the illegal additive chloramphenicol (CAP) was
      successfully detected in aqueous solution with low LOQ and LOD values (1.0 * 10-8
      and 1.0 * 10-10 M, respectively), which was finalized within 10 min based on the
      proposed Dis-MSPME-SERS method. Therefore, a simpler, more efficient and
      sensitive approach to realize enrichment, magnetic separation and detection, all
      in-one, for the detection of illegal additives has been reported, which will be
      promising towards the detection of trace amounts of substance in micro-systems.

PMID- 29345259
TI  - Polymeric carbon nitride nanomesh as an efficient and durable metal-free catalyst
      for oxidative desulfurization.
AB  - We report the first use of polymeric carbon nitride (CN) for the catalytic
      selective oxidation of H2S. The as-prepared CN with unique ultrathin "nanomeshes"
      structure exhibits excellent H2S conversion and high S selectivity. In
      particular, the CN nanomesh also displays better durability in the
      desulfurization reaction than traditional catalysts, such as carbon- and iron
      based materials.

PMID- 29345260
TI  - One-pot chemoenzymatic synthesis of trolline and tetrahydroisoquinoline
      analogues.
AB  - Chemoenzymatic reaction cascades can provide access to chiral compounds from low
      cost starting materials in one pot. Here we describe one-pot asymmetric routes to
      tetrahydroisoquinoline alkaloids (THIAs) using the Pictet-Spenglerase
      norcoclaurine synthase (NCS) followed by a cyclisation, to give alkaloids with
      two new heterocyclic rings. These reactions operated with a high atom economy to
      generate THIAs in high yields.

PMID- 29345261
TI  - An inert 3D emulsification device for individual precipitation and concentration
      of amorphous drug nanoparticles.
AB  - Nanosizing increases the specific surface of drug particles, leading to faster
      dissolution inside the organism and improving the bioavailability of poorly water
      soluble drugs. A novel approach for the preparation of drug nanoparticles in
      water using chemically inert microfluidic emulsification devices is presented in
      this paper. A lithographic fabrication sequence was established, allowing
      fabrication of intersecting and coaxial channels of different depths in glass as
      is required for 3D flow-focusing. Fenofibrate was used as a model for active
      pharmaceutical ingredients with very low water solubility in the experiments. It
      was dissolved in ethyl acetate and emulsified in water, as allowed by the 3D flow
      focusing geometry. In the thread formation regime, the drug solution turned into
      monodisperse droplets of sizes down to below 1 MUm. Fast supersaturation occurs
      individually in each droplet, as the disperse phase solvent progressively
      diffuses into the surrounding water. Liquid antisolvent precipitation results in
      highly monodisperse and amorphous nanoparticles of sizes down to 128 nm which can
      be precisely controlled by the continuous and disperse phase pressure. By
      comparing optically measured droplet sizes with particle sizes by dynamic light
      scattering, we could confirm that exactly one particle forms in every droplet.
      Furthermore, a downstream on-chip concentration allowed withdrawal of major
      volumes of only the continuous phase fluid which enabled an increase of particle
      concentration by up to 250 times.

PMID- 29345262
TI  - Copper(i) complexes with phosphine derived from sparfloxacin. Part III:
      multifaceted cell death and preliminary study of liposomal formulation of
      selected copper(i) complexes.
AB  - The cytotoxic effect of iodide or thiocyanate copper(i) complexes (1-PSf, 2-PSf,
      3-PSf, 4-PSf) with phosphine derived from sparfloxacin (HSf) and 2,9-dimethyl
      1,10-phenanthroline (dmp) or 2,2'-biquinoline (bq) as diimine auxiliary ligands
      was proved in vitro on somatic (MRC-5) and neoplastic (MCF7) human cell lines.
      Differences in mode of action were investigated in-depth for the selected dmp and
      bq complexes (1-PSf, 3-PSf, respectively) by elucidation of the following: (i)
      the efficiency to produce reactive oxygen species (ROS) in biological systems
      (cyclic voltammetry); (ii) their impact on mitochondrial membrane potential;
      (iii) potency for the activation of caspases 3 and 9; (iv) influence on the
      degree of DNA degradation (comet assay). It was concluded that the apoptosis of
      cancer cells is directly connected to the caspase-dependent mitochondrial pathway
      and supported by ROS production along with irreversible DNA fragmentation.
      Finally, it was demonstrated that the selected copper(i) complex encapsulated
      inside liposomes (1-PSf-L) exhibited enhanced accumulation inside cancer cells.
      This resulted in its higher cytotoxicity against cancer cells with therapeutic
      index of ca. 60. Increased selective accumulation in active neoplasm with
      simultaneous enhanced bioavailability and reduced systemic toxicity of liposomal
      formulation of copper(i) complexes can result in the development of new copper
      based therapeutics and their successful implementation in anticancer
      chemotherapy.

PMID- 29345263
TI  - Natural products and ring-closing metathesis: synthesis of sterically congested
      olefins.
AB  - Covering: 2002 to August 2017.This review highlights recent RCM reactions towards
      the synthesis of sterically congested natural products. It offers an insight into
      various synthetic targets and approaches and provides information on the
      evolution of catalysts as powerful tools enabling the use of increasingly
      challenging diene precursors.

PMID- 29345264
TI  - Giant spontaneous exchange bias obtained by tuning magnetic compensation in
      samarium ferrite single crystals.
AB  - Spontaneous exchange bias (SEB) under zero field cooling (ZFC) has recently
      attracted lots of attention due to its underlying physics and potential
      applications. Here we report the giant SEB (GSEB) of SmFeO3 single crystals by
      tuning magnetic compensation by temperature, which is rather convenient. A SEB
      field of up to 1 T at 3.9 K after ZFC (-1.4 T at 3.9 K after field cooling) was
      obtained. The SEB shows reciprocal relationship with remnant magnetization.

PMID- 29345265
TI  - Hierarchical formation of Fe-9eG supramolecular networks via flexible
      coordination bonds.
AB  - From the interplay between high-resolution scanning tunneling microscopy
      imaging/manipulations and density functional theory calculations, we display the
      hierarchical formation of supramolecular networks by codeposition of 9eG
      molecules and Fe atoms on Au(111) based on the flexible coordination bonds (the
      adaptability and versatility in the coordination modes). In the first step,
      homochiral islands composed of homochiral G4Fe2 motifs are formed; and then in
      the second step, thermal treatment results in the transformation into the porous
      networks composed of heterochiral G4Fe2 motifs with the ratio of the components
      being constant. In situ STM manipulations and the coexistence of some other
      heterochiral G4Fe2 motifs and clusters also show the flexibility of the
      coordination bonds involved. These studies may provide a fundamental
      understanding of the regulations of multilevel supramolecular structures and shed
      light on the formation of designed supramolecular nanostructures.

PMID- 29345266
TI  - Efficient interfacial charge transfer through plasmon sensitized Ag@Bi2O3
      hierarchical photoanodes for photoelectrocatalytic degradation of chlorinated
      phenols.
AB  - The present work demonstrates an extremely proficient and robust study of
      efficient interfacial charge transfer through plasmonic Ag decorated Bi2O3
      hierarchical photoanodes for the photoelectrochemical treatment of chlorinated
      phenols. Unique 2D flake-like Bi2O3 hierarchical nanostructures were grown onto a
      fluorine-doped tin oxide (FTO) substrate by a simple chemical bath deposition
      method using triethanolamine as complexing agent. The formation of Bi2O3 on FTO
      was governed by the decomposition of a nucleated bismuth-hydroxyl complex (Bi2O1
      x(OH)x) and modification to the electrode was carried out by the deposition of Ag
      via a chemical reduction method using hydrazine hydrate. Both the fabricated
      electrodes were well characterized for their photo- and electro-optical
      properties. Efficient charge separation was observed due to the surface plasmon
      resonance phenomenon of silver nanoparticles with the favorable intrinsic
      properties of Bi2O3 under application of a small electric bias of 1 V preventing
      the recombination of charge carriers and thereby increasing the rate of
      photoelectrocatalytic degradation of the chlorinated phenols. PEC degradation
      using the Ag@Bi2O3 photoelectrode followed the trend 4-CP < 2,4-DCP < 2,4,6-TCP <
      P-CP due to efficient attack at the chlorinated positions by reactive oxygen
      species with increasing chlorine substitution and also due to the absence of an
      expected chain reaction of the generated chlorine radicals (Cl) during the PEC
      reaction. The PEC activity of Ag@Bi2O3 was 1.5 times higher than a Bi2O3
      nanoflake electrode for 4-CP over 2 h. The fabricated Ag@Bi2O3 proved to be an
      efficient photoelectrode with synergistic solar-induced photoactivity. A detailed
      mechanistic study in the presence of scavengers suggests degradation by produced
      hydroxyl radical species. Thus, physical insights into the degradation of
      chlorinated phenols were obtained.

PMID- 29345267
TI  - Ambient storage of microencapsulated Lactobacillus plantarum ST-III by complex
      coacervation of type-A gelatin and gum arabic.
AB  - Ambient storage of dry powdered probiotics is necessary for manufacturer's cost
      reduction and customer's convenience. Complex coacervation is a promising
      microencapsulation technique. In this work, a probiotic matrix of type-A
      gelatin/gum arabic/sucrose (GE/GA/S) with high coacervation pH was designed,
      based on the alkaline isoelectric point of type-A gelatin. Bacterial survival
      during ambient storage at room temperature and certain relative humidity were
      detected. To clarify the protection factors of the coacervation matrix of
      GE/GA/S, dry microcapsules of GA, GE, GE/sucrose and GE/GA were prepared as
      controls and compared in terms of their morphology, moisture content, dynamic
      vapor absorption and cell viability. Probiotics in GE/GA/S5.5 microcapsules
      behaved the best during spray drying, ambient storage and heat treatment. The
      results proved that sucrose addition was necessary for cell viability against
      environmental stresses, and that encapsulation by complex coacervation was a
      positive factor in cell protection, especially at neutral coacervation pH.

PMID- 29345268
TI  - Homoleptic U(iii) and U(iv) amidate complexes.
AB  - The syntheses of the first homoleptic U(iii) and U(iv) amidate complexes are
      described. These can be interconverted by chemical reduction/oxidation, showing
      an unusual change in coordination number from four in the U(iii) complex to eight
      in the U(iv) complex in the solid state structures.

PMID- 29345269
TI  - Tributyltin induces epigenetic changes and decreases the expression of nuclear
      respiratory factor-1.
AB  - Tributyltin (TBT), a common organotin environmental pollutant, has been widely
      used as a component of marine antifouling paints. We previously reported that
      exposure to TBT inhibits the expression and DNA binding of nuclear respiratory
      factor-1 (NRF-1) and causes neurotoxicity. In the present study, we focused on
      the epigenetic effects of TBT and investigated whether TBT decreases NRF-1
      expression via epigenetic modifications in SH-SY5Y human neuroblastoma cells.
      First, we found that exposure to 300 nM TBT decreases NRF-1 expression. We
      examined epigenetic changes induced by TBT, and showed that TBT causes
      hypermethylation of the NRF-1 promoter region, increases the amount of methyl-CpG
      binding protein 2 (MeCP2) bound to the NRF-1 promoter, and alters the expression
      of DNA methyltransferases and ten-eleven translocation (TET) demethylation
      enzymes. These results suggest that epigenetic changes play an important role in
      regulation of NRF-1 expression. Next, we investigated effect of NRF-1 expression
      decrease on cells, and TBT reduces mitochondrial membrane potential and
      overexpression of NRF-1 rescued this reduction in membrane potential. Thus, we
      suggested that NRF-1 is important for maintaining mitochondrial membrane
      potential. Our study indicates that TBT causes epigenetic changes such as
      hypermethylation, which increases recruitment of MeCP2 to the NRF-1 promoter and
      probably lead to decreased of NRF-1 expression and mitochondrial membrane
      potential. Therefore, this research provides new evidence of the epigenetic
      action caused by organotin.

PMID- 29345270
TI  - Energetics and dynamics of the non-natural fluorescent 4AP:DAP base pair.
AB  - The fluorescent non-natural 4-aminophthalimide (4AP) base, when paired to the
      complementary 2,4-diaminopyrimidine (DAP) nucleobase, is accommodated in a B-DNA
      duplex being efficiently recognized and incorporated by DNA polymerases. To
      complement the experimental studies and rationalize the impact of the above non
      natural bases on the structure, stability and dynamics of nucleic acid
      structures, we performed quantum mechanics (QM) calculations along with classical
      molecular dynamics (MD) simulations. QM calculations were initially focused on
      the geometry and energetics of the 4AP:DAP non-natural pair and of H-bonded base
      pairs between 4AP and all the natural bases in their classical Watson-Crick
      geometries. The QM calculations indicate that the 4AP:DAP pair, despite the fact
      that it can form 3 H-bonds in a classic Watson-Crick geometry, has a stability
      comparable to the A:T pair. Then, we extended the study to reverse Watson-Crick
      geometries, characteristic of parallel strands. MD simulations were carried out
      on two 13-mer DNA duplexes, featuring a central 4AP:DAP or A:T pair,
      respectively. No major structural deformation of the duplex was observed during
      the MD simulation. Snapshots from the MD simulations were subjected to QM
      calculations to investigate the 4AP:DAP interaction energy when embedded into a
      duplex structure, and to investigate the impact of the two non-natural bases on
      the stacking interactions with adjacent bases in the DNA duplex. We found a
      slight increase in stacking interactions involving the 4AP:DAP pair,
      counterbalanced by a moderate decrease in H-bonding interactions of the 4AP:DAP
      and of the adjacent base pairs in the duplex. The results of our study are in
      agreement with experimental data and complement them by providing an insight into
      which factors contribute positively and which factors contribute negatively to
      the structural compatibility of the fluorescent 4AP:DAP pair with a B-DNA
      structure.

PMID- 29345271
TI  - Flocculation on a chip: a novel screening approach to determine floc growth rates
      and select flocculating agents.
AB  - Flocculation is a key purification step in cell-based processes for the food and
      pharmaceutical industry where the removal of cells and cellular debris is aided
      by adding flocculating agents. However, finding the best suited flocculating
      agent and optimal conditions to achieve rapid and effective flocculation is a non
      trivial task. In conventional analytical systems, turbulent mixing creates a
      dynamic equilibrium between floc growth and breakage, constraining the
      determination of floc formation rates. Furthermore, these systems typically rely
      on end-point measurements only. We have successfully developed for the first time
      a microfluidic system for the study of flocculation under well controlled
      conditions. In our microfluidic device (MUFLOC), floc sizes and growth rates were
      monitored in real time using high-speed imaging and computational image analysis.
      The on-line and in situ detection allowed quantification of floc sizes and their
      growth kinetics. This eliminated the issues of sample handling, sample
      dispersion, and end-point measurements. We demonstrated the power of this
      approach by quantifying the growth rates of floc formation under forty different
      growth conditions by varying industrially relevant flocculating agents (pDADMAC,
      PEI, PEG), their concentration and dosage. Growth rates between 12.2 MUm s-1 for
      a strongly cationic flocculant (pDADMAC) and 0.6 MUm s-1 for a non-ionic
      flocculant (PEG) were observed, demonstrating the potential to rank flocculating
      conditions in a quantitative way. We have therefore created a screening tool to
      efficiently compare flocculating agents and rapidly find the best flocculating
      condition, which will significantly accelerate early bioprocess development.

PMID- 29345272
TI  - Preparation of Eu(iii) acetylacetonate-doped well-defined titania particles with
      efficient photoluminescence properties.
AB  - The aggregation/dispersion of luminescent species is a critical factor that
      determines their luminescence properties. In this study, europium(iii)
      acetylacetonate (Eu(acac)3) was doped into a titania matrix to form Eu(acac)3
      doped titania particles with well-defined size and shape through a microreactor
      based sol-gel approach. The morphology and structure of the as-synthesized
      products were characterized by Fourier transform infrared spectroscopy, scanning
      electron microscopy, transmission electron microscopy, scanning transmission
      electron microscopy and X-ray diffraction measurements. The Eu/Ti value of the
      products varied in the range from 0.125 to 5.0 and the resulting luminescence
      properties were examined. It should be noted that there was an optimum Eu/Ti
      value that exhibited the strongest luminescence. A possible reason for this
      phenomenon can be explained on the basis of a balance between the inter-molecular
      distance of Eu(acac)3 and its doped amount. The effects of the crystal phase of
      the titania matrix on luminescence behavior were also investigated. As a result,
      Eu(acac)3-doped amorphous titania demonstrated more efficient luminescence than
      that after calcined at 550  degrees C for 6 h to convert amorphous to anatase
      probably because of the aggregation of Eu species on the crystallite surface. The
      stability of the present Eu(acac)3-doped titania was confirmed by preparing thin
      films on a glass substrate and by applying UV/ozone treatment. As compared to
      bare Eu(acac)3, degradation in luminescence was suppressed in the case of
      Eu(acac)3-doped titania. Thus, the present titania-based hybrid with controlled
      Eu(acac)3 doping is useful as a stable, luminescent material for optical,
      biological and environmental applications.

PMID- 29345283
TI  - Regulation of programmed-death ligand in the human head and neck squamous cell
      carcinoma microenvironment is mediated through matrix metalloproteinase-mediated
      proteolytic cleavage.
AB  - Recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC) is
      a devastating malignancy with a poor prognosis. According to recent clinical
      studies, tumour growth can be effectively reduced and survival can be improved by
      blocking the programmed death receptor-1 (PD-1)/programmed death-ligand 1 (PD-L1)
      pathway. PD-L1 expression has been proposed as a potential causative mechanism,
      as HNSCC is highly immunosuppressive. However, anti-PD-1 treatment is beneficial
      only for certain patients. Therefore, the mechanisms controlling PD-L1 expression
      warrant further investigation in order to provide a better understanding of the
      predicting efficacy of and optimising anti-PD-1 therapy, alone or in combination.
      In this study, PD-L1 protein extracted from the cell membrane was found to be
      downregulated in OSC-20 cells compared with OSC-19 cells, despite a higher PD-L1
      expression in the total cell lysate of the OSC-20 compared with the OSC-19 cells.
      Several matrix metalloproteinases (MMPs) were found to be upregulated in HNSCC;
      in particular, MMP-7 and -13 were upregulated in the OSC-20 compared with the OSC
      19 cells. Purified PD-L1 was degraded by recombinant MMP-13 and -7. The
      expression of PD-L1 was significantly restored by a specific inhibitor of MMP-13
      (CL82198), which suggested the involvement of MMP-13 in the shedding/cleavage of
      PD-L1 in the OSC-20 cells. Among the anticancer drugs conventionally used in the
      treatment of patients with HNSCC, paclitaxel increased MMP-13 expression in R/M
      HNSCC cells (HOC313 cells) co-cultured without/with dendritic cells (DCs). These
      results suggest that the shedding/cleavage of PD-L1 by MMP-13 is one of the
      mechanisms behind the protective effect against invasion and metastasis. Thus,
      MMP-13 has potential value as a marker predictive of the decreased efficacy of
      anti-PD-1 therapy. In addition, paclitaxel is a particularly promising candidate
      for combination therapy in R/M HNSCC with anti-PD-1 therapy.

PMID- 29345284
TI  - Quantitative proteomics analysis of the role of tetraspanin-8 in the drug
      resistance of gastric cancer.
AB  - Gastric cancer, due to its high incidence rate, is the second leading cause of
      cancer-related mortality worldwide. Chemotherapy is an important component of the
      multimodal treatment for gastric cancer; however, a significant impediment to
      successful treatment is multidrug resistance (MDR) in patients with gastric
      cancer. In the present study, the protein profiles of the MDR cell line,
      SGC7901/DDP, and its parental cell line, SGC7901, were comparatively analyzed
      through an iTRAQ-based quantitative proteomics technique. The protein tetraspanin
      8 (TSPAN8) was found to be highly expressed in the SGC7901/DDP cells. To examine
      the role of TSPAN8 in the MDR of SGC7901/DDP cells, we increased cell sensitivity
      to drugs by increasing apoptosis. Additionally, the silencing of TSPAN8
      downregulated Wnt pathway activity, beta-catenin expression and beta-catenin
      transfer to the nucleus. TSPAN8 was found to bind to NOTCH2, facilitating its
      mediation of the Wnt/beta-catenin pathway by regulating beta-catenin expression.
      Overall, the suppression of TSPAN8 expression may prove to be a promising
      strategy which may aid in the development of novel gastric cancer therapeutic
      drugs.

PMID- 29345285
TI  - The epitranscriptome m6A writer METTL3 promotes chemo- and radioresistance in
      pancreatic cancer cells.
AB  - N6-methyladenosine (m6A) is the most abundant epitranscriptome modification in
      mammalian mRNA. Recent years have seen substantial progress in m6A
      epitranscriptomics, indicating its crucial roles in the initiation and
      progression of cancer through regulation of RNA stabilities, mRNA splicing,
      microRNA processing and mRNA translation. However, by what means m6A is
      dynamically regulated or written by enzymatic components represented by
      methyltransferase-like 3 (METTL3) and how m6A is significant for each of the
      numerous genes remain unclear. We focused on METTL3 in pancreatic cancer, the
      prognosis of which is not satisfactory despite the development of
      multidisciplinary therapies. We established METTL3-knockdown pancreatic cancer
      cell line using short hairpin RNA. Although morphologic and proliferative changes
      were unaffected, METTL3-depleted cells showed higher sensitivity to anticancer
      reagents such as gemcitabine, 5-fluorouracil, cisplatin and irradiation. Our data
      suggest that METTL3 is a potent target for enhancing therapeutic efficacy in
      patients with pancreatic cancer. In addition, we performed cDNA expression
      analysis followed by gene ontology and protein-protein interaction analysis using
      the Database for Annotation, Visualization, and Integrated Discovery and Search
      Tool for the Retrieval of Interacting Genes/Proteins databases, respectively. The
      results demonstrate that METTL3 was associated with mitogen-activated protein
      kinase cascades, ubiquitin-dependent process and RNA splicing and regulation of
      cellular process, suggesting functional roles and targets of METTL3.

PMID- 29345286
TI  - Cyclooxygenase-2 expression is induced by celecoxib treatment in lung cancer
      cells and is transferred to neighbor cells via exosomes.
AB  - Lung cancer is one of most common types of cancer worldwide. Lung cancer results
      in a death higher rate each year compared to colon, breast and prostate cancer
      combined. Celecoxib is a selective inhibitor of cyclooxygenase-2 (COX-2), an
      enzyme of which the expression is induced by various stimuli, such as
      inflammation. In addition, celecoxib triggers COX-2 loading on exosomes. Exosomes
      are small vesicles composed of a lipid bilayer membrane and are found in most
      biological fluids, such as blood breast milk and urine. In this study, we focused
      on exosomes containing COX-2 proteins from lung cancer cells to determine their
      involvement in the interaction with neighbor cells following treatment with
      celecoxib. We found that celecoxib induced COX-2 expression in both the cytosol
      and exosomes in lung cancer cells. Exosomes from celecoxib-treated lung cancer
      cell culture supernatant were isolated and incubated with several types of cells.
      The THP-1, monocytic leukemia cell line effectively absorbed COX-2 by lung cancer
      cell-derived exosomes. Following incubation with exosomes, the COX-2 protein
      level was increased in the THP-1 cells; however, COX-2 mRNA expression was not
      affected. Moreover, prostaglandin E2 (PGE2) and vascular endothelial growth
      factor (VEGF) production by THP-1 cells was increased following incubation with
      exosomes from celecoxib-treated lung cancer cells. Conditioned medium from THP-1
      following incubation with exosomes promoted formation in EA.hy926 cells. Taken
      together, our findings suggest that celecoxib induces COX-2 expression in lung
      cancer cells, and that highly expressed COX-2 in exosomes can be transferred to
      other cells.

PMID- 29345287
TI  - Intermittent calorie restriction enhances epithelial-mesenchymal transition
      through the alteration of energy metabolism in a mouse tumor model.
AB  - The effect of intermittent calorie restriction (ICR) on cancer is controversial.
      In this study, we examined the effects of ICR and food content in syngeneic
      BALB/c mice injected with CT26 mouse colon cancer cells. Mice were subjected to
      24-h fasting once a week for 4 weeks, and then provided with a control, high
      calorie, or trans fatty acid-rich diet. While ICR resulted in increases in tumor
      weights, metastasis and in the number of cancer stem cells (CSCs) in the tumors
      or blood of mice fed the control and high-fat diets, it had no effect on body
      weight after 4 weeks. In particular, we detected increases in the numbers of CSCs
      in the tumor or blood on the day after starvation, when food overconsumption was
      detected. Conversely, continuous calorie restriction had no effect on tumor
      weight, metastasis, or the number of CSCs in tumors or blood. In the post
      starvation period, energy metabolism in the tumor was altered from oxidative
      phosphorylation to glycolysis/lactate fermentation, with the acquisition of the
      epithelial-mesenchymal transition (EMT) phenotype. Hyperglycemia at the post
      starvation period induced the expression of insulin-like growth factor-1, hypoxia
      induced factor-1alpha and Nanog, as well as the phosphorylation of Stat3. Taken
      together, these findings suggest that ICR induces an increase in the number of
      CSCs and enhances EMT by promoting the Warburg/Crabtree effect following post
      fasting food overconsumption.

PMID- 29345288
TI  - Downregulation of miR-205 is associated with glioblastoma cell migration,
      invasion, and the epithelial-mesenchymal transition, by targeting ZEB1 via the
      Akt/mTOR signaling pathway.
AB  - Glioblastoma (GBM) is the most common type of malignant brain tumor. In spite of
      recent advancements in surgical techniques, chemotherapy, and radiation therapy,
      patients with GBM often face a dire prognosis. MicroRNAs have been shown to
      modulate the aggressiveness of various cancers, and have emerged as possible
      therapeutic agents for the management of GBM. miR-205 is dysregulated in glioma
      and act as a prognostic indicator. However, the role of miR-205 in the
      development of GBM has not been elucidated. To better understand the pathogenesis
      of GBM, we examine the biological significance and molecular mechanisms of miR
      205 in GBM cells. Zinc finger E-box binding homeobox 1 (ZEB1) has been shown to
      regulate the epithelial-mesenchymal transition (EMT), which is strongly
      associated with GBM malignancy. In the present study, we show miR-205 expression
      is reduced in GBM tissues and cell lines, and ZEB1 expression is inversely
      correlated with miR-205 expression. We also show ZEB1 is a downstream target of
      miR-205 and the Akt/mTOR signaling pathway is activated when miR-205 interacts
      with ZEB1. Increased activity of miR-205 in GBM cells significantly inhibits
      migration and invasion, and prevents EMT. Furthermore, overexpression of ZEB1
      partially abolishes these inhibitory effects of miR-205. We show that miR-205
      negatively regulates the expression of ZEB1 in GBM, inhibits cell migration and
      invasion, and prevents EMT, at least in part through the inhibition of the
      activation of the Akt/mTOR signaling pathway. Our results indicate miR-205 may be
      an efficacious therapeutic agent in the treatment of GBM.

PMID- 29345289
TI  - No erythropoietin-induced growth is observed in non-small cell lung cancer cells.
AB  - Lung cancer patients have the highest incidence of anemia among patients with
      solid tumors. The use of recombinant human erythropoietin (Epo) has consistently
      been shown to reduce the need for blood transfusions and to increase hemoglobin
      levels in lung cancer patients with chemotherapy-induced anemia. However,
      clinical and preclinical studies have prompted concerns that Epo and the presence
      of its receptor, EpoR, in tumor cells may be responsible for adverse effects and,
      eventually, death. The question has been raised whether Epo promotes tumor growth
      and inhibits the death of cancer cells. In this study, we investigated the
      presence and functionality of EpoR, as well as the implications of Epo upon the
      proliferation and survival of lung cancer cells. Since the protein expression of
      both Epo and EpoR is induced by hypoxia, which is frequently present in lung
      cancer, the cells were treated with Epo under both normoxic and hypoxic
      conditions (1% O2). By using quantitative (real-time) PCR, western blot analysis,
      and immunocytochemical staining, three non-small cell lung cancer (NSCLC) cell
      lines (A427, A549 and NCI-H358) were analyzed for the expression of EpoR and its
      specific downstream signaling pathways [Janus kinase 2 (Jak2)-signal transducer
      and activator of transcription 5 (STAT5), phosphatidylinositol-3-kinase (PI3K)
      Akt, mitogen-activated protein (MAP) kinase]. The effects of 100 U/ml Epo on cell
      proliferation and cisplatin-induced apoptosis were assessed. All NSCLC cell lines
      expressed EpoR mRNA and protein, while these levels differed considerably between
      the cell lines. We found the constitutive phosphorylation of EpoR and most of its
      downstream signaling pathways (STAT5, Akt and ERK1/2) independently of Epo
      administration. While Epo markedly enhanced the proliferation and reduced
      apoptosis of Epo-dependent UT-7/Epo leukemia cells, it did not affect tumor cell
      proliferation or the cisplatin-induced apoptosis of NSCLC cells. Thus, this in
      vitro study suggests that there are no tumor-promoting effects of Epo in the
      NSCLC cell lines studied, neither under normoxic nor under hypoxic conditions.

PMID- 29345290
TI  - Role of nestin expression in angiogenesis and breast cancer progression.
AB  - Nestin is an intermediate filament protein and a stem cell marker expressed in
      several tumours. There is growing evidence of an association between the
      expression level of nestin and the pathogenesis of triple-negative breast cancer
      (TNBC). Nestin is also expressed in newly forming tumour vessels and is a
      valuable marker of ongoing angiogenesis. In this study, we aimed to evaluate the
      prognostic value of nestin expression in breast tumour cells and to determine
      whether this expression influences angiogenesis. Immunohistochemical (IHC)
      analyses were carried out on 124 cases of invasive ductal carcinoma (IDC) of the
      breast with a panel of murine monoclonal antibodies against nestin, CD31, CD34,
      SOX-18 and Ki-67. We evaluated nestin expression in tumour and endothelial cells,
      Ki-67 in tumour cells, and CD31, CD34 and SOX-18 in endothelial cells. Our
      results demonstrated that nestin expression in tumour cells correlated with the
      area and number of vessels expressing nestin, CD31, CD34 and SOX-18. We also
      found a positive correlation between nestin-expressing vessels and SOX-18
      expressing vessels. Our results are consistent with those of previous studies, in
      which nestin expression in endothelial cells was shown to be strongly associated
      with triple-negative subtype, poorly differentiated G3 tumours, a higher
      proliferation index and a shorter overall survival. Nestin expression was also
      examined in human breast cancer cell lines (MCF-7, SK-BR-3, MDA-MB-231 and BO2
      cells) representing a different level of tumour aggressiveness and reflecting
      histological grade. A higher nestin protein level was observed in more aggressive
      MDA-MB-231 and BO2 cells than in MCF-7 and SK-BR-3 cells.

PMID- 29345291
TI  - MicroRNA-1271 functions as a metastasis and epithelial-mesenchymal transition
      inhibitor in human HCC by targeting the PTP4A1/c-Src axis.
AB  - MicroRNAs (miRNAs or miRs) have been shown to regulate hepatocellular carcinoma
      (HCC) metastasis. In the present study, we focused on the functions of miR-1271
      in HCC metastasis. The downregulation of miR-1271 was found to be associated with
      to venous infiltration, an advanced TNM stage (III+IV stage) and a shorter
      survival time. Our in vitro and in vivo data demonstrated that miR-1271 prevented
      HCC cell migration and invasion, as well as the formation of lung metastatic
      clusters. In addition, miR-1271 was demonstrated to markedly inhibit the
      epithelial-mesenchymal transition (EMT) of HCC cells. Importantly, protein
      tyrosine phosphatase type IVA member 1 (PTP4A1) was identified as a direct
      downstream target of miR-1271 in HCC. Furthermore, we confirmed that the
      phosphorylation of c-Src at Tyr416 mediated by PTP4A1 was a potential anti-HCC
      mechanism of action of miR-1271. On the whole, our data indicate that miR-1271
      inhibits HCC metastasis by targeting the PTP4A1/c-Src signaling pathway and may
      serve as a prospective cancer therapeutic target for HCC.

PMID- 29345292
TI  - Preparation and characterization of the antibody recognizing AMACR inside its
      catalytic center.
AB  - Alpha-methylacyl-CoA racemase (AMACR) catalyzes the beta-oxidation of fatty acids
      and is overexpressed in carcinomas in various organs, while its inactivation
      results in the inhibition of cancer growth. In the present study, we prepared and
      characterized 20 different mouse monoclonal antibodies against human AMACR. In
      the course of biopanning of a phage peptide commercial library against in-house
      prepared 6H9 and 2A5, and commercial 13H4 antibodies, 10 phage mimotopes
      recognized by each type of the antibody were selected. Using the program Pepitope
      and the crystal structure of AMACR from Mycobacterium tuberculosis, we reveal for
      the first time, at least to the best of our knowledge, that the epitopes
      recognizing the antibody against AMACR are composed of conformation sequences
      localized inside the AMACR catalytic center. When delivered into live HeLa cells
      using cationic lipid-based PULSin reagent, the specific antibodies against AMACR
      were co-localized with peroxisomes. The in-house made 6H9 antibody exhibited a
      low level of this co-localization compared to the commercially available 63340
      antibody, and did not inhibit the growth rate of HeLa and T98G cells. The results
      obtained suggest that antibody against AMACR may possess anti-AMACR catalytic
      activity and needs to be further investigated as a potential drug for use in
      anticancer therapy. On the whole, in this study, we generated several clones of
      AMACR antibodies and demonstrated that these antibodies can be colonized into
      live cells. Currently, we are testing the growth inhibitory properties of these
      antibodies against AMACR.

PMID- 29345293
TI  - S100B expression in breast cancer as a predictive marker for cancer metastasis.
AB  - In the tumor microenvironment, soluble molecules play important role in the
      establishment of a pre-metastatic niche. The S100 calcium-binding protein family
      are inflammatory molecules that contribute to the development of a pro
      inflammatory tumor microenvironment. S100B belongs to the S100 family and serum
      S100B (also known as S100beta) serves as a marker for metastasis in lung cancer,
      ovarian cancer and melanoma. However, the association between S100B and the
      metastasis of breast cancer is not yet well understood. In the present study, a
      relatively low S100B expression was observed in the tumor samples compared to
      normal breast tissue among online microarray datasets. When the estrogen receptor
      (ER)-negative breast cancer cell lines, MDA-MB-231 and Hs578T, were treated with
      recombinant human S100B, cell migration was significantly inhibited and
      epithelial cadherin expression was increased. Our results revealed that a high
      S100B expression predicted a good overall survival in patients with ER-negative
      breast cancer, and good distant metastases-free survival in all patients with
      breast cancer via the analysis of the KM plotter and SurvExpress databases.
      Although previous studies have indicated that the interaction of S100B with wild
      type p53 inhibits p53 function, a high S100B expression is associated with a good
      prognosis in patients with p53 mutant and p53 wild-type breast cancers. On the
      whole, our findings demonstrate that S100B treatment suppresses the migratory
      capacity of ER-negative breast cancer and that S100B expression may serve a
      predictive marker for metastasis in breast cancer.

PMID- 29345294
TI  - Hypoxia stimulates the cytoplasmic localization of oncogenic long noncoding RNA
      LINC00152 in colorectal cancer.
AB  - Recent studies have indicated that long noncoding RNAs (lncRNAs) play a pivotal
      role in almost all physiological cellular processes, including every stage of
      cancer development. Given that hypoxia in the tumor microenvironment is involved
      in the malignant behavior of tumors, such as invasion and metastasis, we
      investigated the cytoplasmic and nuclear localization of lncRNAs in colorectal
      cancer cells. A cell culture under hypoxic conditions revealed several lncRNAs,
      such as LINC00152, whose levels were increased in the cytoplasm of colorectal
      cancer cells. A database study indicated that LINC00152 shares microRNA-binding
      sites, such as miR-138 and miR-193, with the hypoxia-inducible factor 1 (HIF1),
      thus suggesting that LINC00152 could possibly function as a competing endogenous
      RNA that can augment Hif1 translation in the cytoplasm of hypoxic colorectal
      cancer cells. Moreover, the data presented in the studies of surgically resected
      samples showed that patients with colorectal cancer exhibiting high LINC00152
      expression were associated with a worsened survival rate; this supports the
      suggested oncogenic function of LINC00152 in the cytoplasm under hypoxic
      conditions. The present study demonstrated that lncRNA networks could provide
      diagnostic tools and novel therapeutic targets against colorectal cancer cells.

PMID- 29345295
TI  - Upregulation of the BDNF/TrKB pathway promotes epithelial-mesenchymal transition,
      as well as the migration and invasion of cervical cancer.
AB  - Brain-derived neurotrophic factor (BDNF) has previously been demonstrated to be
      associated with several types of cancer. In addition, its receptor, tropomyosin
      related kinase B (TrkB) is involved in tumor invasion and metastasis. Epithelial
      mesenchymal transition (EMT) is associated with metastasis in cancers. Thus, The
      aim of the present study was to examine whether BDNF/TrKB expression is linked to
      a poor survival and the acquisition of the EMT phenotype in cervical cancer. We
      found that a high positive expression of BDNF/TrKB was associated with poor
      survival in cervical cancer. Our results revealed that high expression levels of
      BDNF/TrKB were observed in cervical cancer compared to normal cells. Importantly,
      we demonstrated that the silencing of TrKB suppressed the activation of EMT via
      the downregulation of N-cadherin, vimentin, matrix metalloproteinase (MMP)2 and
      MMP9, and the upregulation of E-cadherin and tissue inhibitor of
      metalloproteinases (TIMP)2, which resulted in suppressed cell proliferation,
      migration and invasion. Furthermore, high phosphorylation levels of ERK and Akt
      were observed in the cervical cancer cells, while these levels were decreased in
      the cells in which TrKB was knocked down. On the whole, these findings suggest
      that the BDNF/TrKB pathway is a promising target for the prevention of tumor
      proliferation, invasion, metastasis and EMT in cervical cancer cells.

PMID- 29345297
TI  - miR-135b-5p promotes gastric cancer progression by targeting CMTM3.
AB  - CKLF-like MARVEL transmembrane domain containing 3 (CMTM3) is considered to be a
      tumor suppressor gene in multiple types of malignancies. Previous studies have
      indicated that CMTM3 suppresses metastasis and epithelial-mesenchymal transition
      (EMT) in gastric cancer. However, its role in gastric cancer cell proliferation
      has rarely been discussed. Moreover, the regulatory mechanisms of CMTM3 in
      gastric cancer remain unclear. In this study, RT-qPCR and IHC were used to assess
      the expression of CMTM3 and miR-135b-5p in gastric cancer tissues and cell lines.
      We found that the expression of miR-135b-5p was negatively associated with CMTM3
      in gastric cancer tissues, and we verified that miR-135b-5p directly targeted
      CMTM3 in gastric cancer cells by dual-luciferase reporter assay. CCK8 assay,
      Transwell assay and flow cytometric analysis were conducted to examine the
      functions of CMTM3 and miR-135b-5p in vitro. Our results demonstrated that the
      overexpression of CMTM3 or the suppression of miR-135b-5p using an inhibitor
      suppressed SGC-7901 gastric cancer cell proliferation, invasion and cell cycle
      progression, and promoted SGC-7901 cell apoptosis. Furthermore, a BALB/c nude
      mouse subcutaneous xenograft model was used to verify the function of miR-135b-5p
      and CMTM3. Our results revealed that miR-135b-5p inhibitor significantly
      suppressed SGC-7901 cell tumorigenesis in vivo. In addition, IHC revealed that
      CMTM3 expression was markedly increased in tumors infected with miR-135b-5p
      inhibitor lentivirus. On the whole, the findings of the present study suggest
      that the overexpression of miR-135b-5p inhibits CMTM3 expression, and promotes
      gastric cancer progression and metastasis. Our findings provide a novel
      therapeutic target for gastric cancer.

PMID- 29345298
TI  - Leishmania amazonensis isolated from human visceral leishmaniasis:
      histopathological analysis and parasitological burden in different inbred mice.
AB  - Leishmania amazonensis is a major etiological agent of human cutaneous
      leishmaniasis in the Americas; nevertheless there are some reports of this
      species causing visceral disease in dogs and men. In the present work we have
      studied a Leishmania strain isolated from a human case of visceral leishmaniasis.
      We have infected different mouse strains and analyzed the development of the
      disease, studying the parasite's ability to visceralize and whether this ability
      is influenced by host genetics. Female BALB/c, C57BL/6, C57BL/10, CBA, DBA/2, and
      C3H/He mice were subcutaneously infected with 104 L. amazonensis amastigotes.
      BALB/c, C57BL/6 and C57BL/10 mice were found to be very susceptible to infection,
      showing lesions that developed to necrosis and ulceration. CBA mice developed a
      late but severe lesion. DBA/2 mice developed only discrete lesions, while C3H/He
      mice did not develop any lesions. All mouse strains except C3H/He showed some
      degree of visceralization, presenting parasites in the spleen, while BALB/c,
      C57BL/6 and CBA presented parasites also in the liver. Moreover, most of the
      strains presented high parasite load at the infection site, whereas DBA and
      C3H/He mice showed low or no parasite load 90 days after infection, respectively.
      Histopathology corroborates the results, showing that susceptible mice presented
      an inflammatory reaction with parasites in the skin, lymph nodes and spleen,
      while strains that are more resistant presented low parasitism and discrete
      inflammatory reaction. Results indicate that this isolate is extremely virulent,
      can easily visceralize and that the pathogenesis of leishmaniasis is, at least in
      part, related to the genetic background of the host.

PMID- 29345299
TI  - The continuing misuse of null hypothesis significance testing in biological
      anthropology.
AB  - There is over 60 years of discussion in the statistical literature concerning the
      misuse and limitations of null hypothesis significance tests (NHST). Based on the
      prevalence of NHST in biological anthropology research, it appears that the
      discipline generally is unaware of these concerns. The p values used in NHST
      usually are interpreted incorrectly. A p value indicates the probability of the
      data given the null hypothesis. It should not be interpreted as the probability
      that the null hypothesis is true or as evidence for or against any specific
      alternative to the null hypothesis. P values are a function of both the sample
      size and the effect size, and therefore do not indicate whether the effect
      observed in the study is important, large, or small. P values have poor
      replicability in repeated experiments. The distribution of p values is continuous
      and varies from 0 to 1.0. The use of a cut-off, generally p <= 0.05, to separate
      significant from nonsignificant results, is an arbitrary dichotomization of
      continuous variation. In 2016, the American Statistical Association issued a
      statement of principles regarding the misinterpretation of NHST, the first time
      it has done so regarding a specific statistical procedure in its 180-year
      history. Effect sizes and confidence intervals, which can be calculated for any
      data used to calculate p values, provide more and better information about tested
      hypotheses than p values and NHST.

PMID- 29345296
TI  - Vitamin D derivatives potentiate the anticancer and anti-angiogenic activity of
      tyrosine kinase inhibitors in combination with cytostatic drugs in an A549 non
      small cell lung cancer model.
AB  - Numerous in vitro and in vivo studies have demonstrated that calcitriol
      [1,25(OH)2D3] and different vitamin D analogs possess antineoplastic activity,
      regulating proliferation, differentiation and apoptosis, as well as angiogenesis.
      Vitamin D compounds have been shown to exert synergistic effects when used in
      combination with different agents used in anticancer therapies in different
      cancer models. The aim of this study was to evaluate the mechanisms of the
      cooperation of the vitamin D compounds [1,24(OH)2D3 (PRI-2191) and 1,25(OH)2D3]
      with tyrosine kinase inhibitors (imatinib and sunitinib) together with
      cytostatics (cisplatin and docetaxel) in an A549 non-small cell lung cancer
      model. The cytotoxic effects of the test compounds used in different combinations
      were evaluated on A549 lung cancer cells, as well as on human lung microvascular
      endothelial cells (HLMECs). The effects of such combinations on the cell cycle
      and cell death were also determined. In addition, changes in the expression of
      proteins involved in cell cycle regulation, angiogenesis and the action of
      vitamin D were analyzed. Moreover, the effects of 1,24(OH)2D3 on the anticancer
      activity of sunitinib and sunitinib in combination with docetaxel were examined
      in an A549 lung cancer model in vivo. Experiments aiming at evaluating the
      cytotoxicity of the combinations of the test agents revealed that imatinib and
      sunitinib together with cisplatin or docetaxel exerted potent anti-proliferative
      effects in vitro on A549 lung cancer cells and in HLMECs; however, 1,24(OH)2D3
      and 1,25(OH)2D3 enhanced the cytotoxic effects only in the endothelial cells.
      Among the test agents, sunitinib and cisplatin decreased the secretion of
      vascular endothelial growth factor (VEGF)-A from the A549 lung cancer cells. The
      decrease in the VEGF-A level following incubation with cisplatin correlated with
      a higher p53 protein expression, while no such correlation was observed following
      treatment of the A549 cells with sunitinib. Sunitinib together with docetaxel and
      1,24(OH)2D3 exhibited a more potent anticancer activity in the A549 lung cancer
      model compared to double combinations and to treatment with the compounds alone.
      The observed anticancer activity may be the result of the influence of the test
      agents on the process of tumor angiogenesis, for example, through the
      downregulation of VEGF-A expression in tumor and also on the induction of cell
      death inside the tumor.

PMID- 29345300
TI  - Angiosarcoma following treatment of basal cell carcinoma: a report of two cases.

PMID- 29345301
TI  - Diphenylcyclopropenone-induced psoriatic koebnerization.

PMID- 29345302
TI  - Body mass prediction from femoral volume and sixteen other femoral variables in
      the elderly: BMI and adipose tissue effects.
AB  - OBJECTIVES: The frequently used prediction equations of body mass do not seem
      appropriate for elderly individuals. Here, we establish the relationship between
      femoral dimensions and known body mass in elderly individuals in order to develop
      prediction formulas and identify the factors affecting their accuracy. MATERIALS
      AND METHODS: The body mass linear least-squares regression is based on 17 femoral
      dimensions, including femoral volume, and 66 individuals. Body proportion and
      composition effects on accuracy are analyzed by means of the body mass index
      (BMI) and on a subset sample (n = 25), by means of the masses of adipose, bone
      and muscle tissues. RESULTS: Most variables significantly reflect body mass.
      Among them, six dimensions (e.g., biepicondylar breadth, femoral volume, and head
      femoral diameter) present percent standard errors of estimate ranging from 9.5 to
      11% (r = 0.72-0.81) in normal BMI samples. Correlations are clearly lower in
      samples with normal and abnormal BMI [r = 0.38-0.58; % of standard error of
      estimate (SEE) = 17.3-19.6%] and not significantly correlated in females (femoral
      volume) who present high proportions of abnormal BMI and adipose tissue. In the
      subset, femoral volume is well correlated with bone mass (r = 0.88; %SEE = 7.9%)
      and lean body mass (r = 0.67; %SEE = 17.2%). DISCUSSION: Our body mass estimation
      equations for elderly individuals are relevant since relatively low correlations
      are recurrent in studies using younger individuals of known body mass. However,
      age, sex, lifestyle, and skeleton considerations of studied populations can
      provide information about the relevance of the body mass estimation, which is
      dependent on the BMI classification and the proportion of adipose tissue. Our
      general considerations can be used for studies of younger individuals.

PMID- 29345303
TI  - Divided nevus of the penis.

PMID- 29345304
TI  - Toward more robust plant-soil feedback research.
AB  - Understanding if and how plant-soil biota feedbacks (PSFs) shape plant
      communities has become a major research priority. In this paper, we draw on a
      recent, high-profile PSF study to illustrate that certain widely used
      experimental methods cannot reliably determine if PSFs occur. One problem
      involves gathering soil samples adjacent to multiple conditioning plants, mixing
      the samples and then growing phytometers in the mixtures to test for PSFs. This
      mixed soil approach does not establish that the conditioning plant being present
      caused the soil biota to be present, the first step of a PSF. Also, soil mixing
      approximates replacing raw data with averages prior to analysis, a move certain
      to generate falsely precise statistical estimates. False precision also results
      from sample sizes being artificially inflated when phytometers are misinterpreted
      as experimental units. Plant biomass ratios become another source of false
      precision when individual plant values contribute to multiple ratio observations.
      Any one of these common missteps can cause still living null hypotheses to be
      pronounced dead, and risks of this increase with numbers of missteps. If soil
      organisms truly structure plant communities, then null hypotheses indicating
      otherwise will not survive proper testing. We discuss conceptual, experimental
      and analytical refinements to facilitate accurate testing.

PMID- 29345305
TI  - Detection of mitochondrial haplogroups in a small avar-slavic population from the
      eigth-ninth century AD.
AB  - OBJECTIVES: In the sixth century AD, Avars came to Central Europe from middle
      Eurasian steppes and founded a strong Empire called the Avar Khagante (568
      799/803 AD) in the Pannonian basin. During the existence of this empire, they
      undertook many military and pugnacious campaigns. In the seventh century, they
      conquered the northern territory inhabited by Slavs, who were further recruited
      in Avar military and were commissioned with obtaining food supplies. During
      almost 200 years of Avar domination, a significant influence by the Avar culture
      (especially on the burial rite) and assimilation with indigenous population
      (occurrence of "East Asian"cranial features) could be noticed in this mixed area,
      which is supported by achaeological and anthropologcal research. Therefore we
      expected higher incidence of east Eurasian haplogroups (introduced by Avars) than
      the frequencies detected in present-day central European populations. MATERIALS
      AND METHODS: Mitochondrial DNA from 62 human skeletal remains excavated from the
      Avar-Slavic burial site Cifer-Pac (Slovakia) dated to the eighth and ninth
      century was analyzed by the sequencing of hypervariable region I and selected
      parts of coding region. Obtained haplotypes were compared with other present-day
      and historical populations and genetic distances were calculated using standard
      statistical method. RESULTS AND DISCUSSION: In total, the detection of
      mitochondrial haplogroups was possible in 46 individuals. Our results prooved a
      higher frequency of east Eurasian haplogroups in our analyzed population (6.52%)
      than in present-day central European populations. However, it is almost three
      times lower than the frequency of east Eurasian haplogroups detected in other
      medieval Avar populations. The statistical analysis showed a greater similarity
      and the lowest genetic distances between the Avar-Slavic burial site Cifer-Pac
      and medieval European populations than the South Siberian, East and Central Asian
      populations. CONCLUSION: Our results indicate that the transfer of Avar genetic
      variation through their mtDNA was rather weak in the analyzed mixed population.

PMID- 29345306
TI  - Hypoalbuminaemia segregates different prognostic subgroups within the refined
      standard risk acute graft-versus-host disease score.
AB  - Hypoalbuminaemia has been previously described to predict worse non-relapse
      mortality (NRM) and inferior overall survival (OS) in allogeneic haematopoietic
      cell transplant (allo-HCT) recipients. Here, we evaluate the role of
      hypoalbuminaemia (<35 g/l) at time of onset of acute graft-versus-host disease
      (aGVHD) when incorporated into the refined aGVHD score. The study population
      consisted of 522 patients, median age 53 (18-75) years, who underwent an allo-HCT
      mostly for haematological malignancies. Standard risk (SR) aGVHD comprised 467
      patients (89%) and the number of high risk (HR) cases was 55 (11%). Median follow
      up for all surviving patients was 26 (3-55) months. Two-year OS was significantly
      better in patients with SR aGVHD with a serum albumin >=35 g/l compared to SR
      with albumin <35 g/l [70% (95% CI = 64-76%) vs. 49% (95% CI = 42-56%), P <
      0.0001]. Also, patients with SR aGVHD and a serum albumin level of >=35 g/l had a
      significantly lower NRM at 1-year post-transplantation [6% (95% CI = 3-10%) vs.
      25% (95% CI = 20-32%), P < 0.0001]. After our findings are validated in a large
      cohort of patients, we propose that hypoalbuminaemia should be incorporated into
      the refined aGVHD risk score to further its ability to predict outcomes within
      this group.

PMID- 29345307
TI  - Competitive ability, stress tolerance and plant interactions along stress
      gradients.
AB  - Exceptions to the generality of the stress-gradient hypothesis (SGH) may be
      reconciled by considering species-specific traits and stress tolerance
      strategies. Studies have tested stress tolerance and competitive ability in
      mediating interaction outcomes, but few have incorporated this to predict how
      species interactions shift between competition and facilitation along stress
      gradients. We used field surveys, salt tolerance and competition experiments to
      develop a predictive model interspecific interaction shifts across salinity
      stress gradients. Field survey and greenhouse tolerance tests revealed tradeoffs
      between stress tolerance and competitive ability. Modeling showed that along
      salinity gradients, (1) plant interactions shifted from competition to
      facilitation at high salinities within the physiological limits of salt
      intolerant plants, (2) facilitation collapsed when salinity stress exceeded the
      physiological tolerance of salt-intolerant plants, and (3) neighbor removal
      experiments overestimate interspecific facilitation by including intraspecific
      effects. A community-level field experiment, suggested that (1) species
      interactions are competitive in benign and, facilitative in harsh condition, but
      fuzzy under medium environmental stress due to niche differences of species and
      weak stress amelioration, and (2) the SGH works on strong but not weak stress
      gradients, so SGH confusion arises when it is applied across questionable stress
      gradients. Our study clarifies how species interactions vary along stress
      gradients. Moving forward, focusing on SGH applications rather than exceptions on
      weak or nonexistent gradients would be most productive.

PMID- 29345308
TI  - Positive size-speed relationships in gametes and vegetative cells of
      Chlamydomonas reinhardtii; implications for the evolution of sperm.
AB  - It is commonly held that differences in gametes of the two sexes (anisogamy)
      evolved from ancestors whose gametes were similar in size and behavior (isogamy).
      Underlying many hypotheses explaining anisogamy are assumed relationships between
      cell size and speed in the ancestral isogamous population. Using the isogamous
      alga Chlamydomonas reinhardtii, we explored size-speed distributions in
      vegetative and gamete cells of 10 cell lines, and clonal data from within two
      cell lines. We applied an independent speed selection approach to gamete
      populations of C. reinhardtii, monitoring correlated responses in size following
      selection for high speed. We demonstrate positive size-speed relationships in
      clones, cell lines, and artificially selected speed selection lines. We found
      different size-speed relationships in the two cell types of C. reinhardtii even
      though they overlap in size, suggesting that cell composition and/or programs of
      gene expression are capable of altering this relationship, and that the
      relationship is evolvable. The positive genetic size-speed correlation means that
      the division of parent vegetative cells into numerous gametes trades off against
      not only size, but also speed, a trade-off that has not received previous
      attention. Our results support reevaluating the role of speed selection in the
      evolution of anisogamy.

PMID- 29345309
TI  - Microbial mitigation-exacerbation continuum: a novel framework for microbiome
      effects on hosts in the face of stress.
AB  - A key challenge to understanding microbiomes and their role in ecological
      processes is contextualizing their effects on host organisms, particularly when
      faced with environmental stress. One influential theory, the Stress Gradient
      Hypothesis, might predict that the frequency of positive interactions increases
      with stressful conditions such that microbial taxa would mitigate harmful effects
      on host performance. Yet, equally plausible is that microbial taxa could
      exacerbate these effects. Here, we introduce the Mitigation-Exacerbation
      Continuum as a novel framework to conceptualize microbial mediation of stress. We
      (1) use this continuum to quantify microbial mediation of stress for six plant
      species and (2) test the association between these continuum values and natural
      species' abundance. We factorially manipulated a common stress (allelopathy) and
      the presence of soil microbes to quantify microbial effects in benign and
      stressed environments for two critical early life-history metrics, seed
      germination and seedling biomass. Although we found evidence of both mitigation
      and exacerbation among the six species, exacerbation was more common. Across
      species, the degree of microbial-mediated effects on germination explained >80%
      of the variation of natural field abundances. Our results suggest a critical role
      of soil microbes in mediating plant stress responses, and a potential microbial
      mechanism underlying species abundance.

PMID- 29345310
TI  - A potential role of knockout serum replacement as a porcine follicular fluid
      substitute for in vitro maturation: Lipid metabolism approach.
AB  - The use of supplements, such as porcine follicular fluid (pFF), fetal bovine
      serum and human serum albumin are widely used during in vitro maturation (IVM) in
      different species but these supplements contain undefined components that cause
      technical difficulties in standardization and influence the efficiency of IVM.
      Knockout serum replacement (KSR) is a synthetic protein source, without any
      undefined growth factors or differentiation-promoting factors. Therefore, it is
      feasible to use KSR as a defined component for avoiding effects of unknown
      molecules in an IVM system. In this study, the rates of oocyte maturation and
      blastocyst formation after parthenogenetic activation (PA), somatic cell nuclear
      transfer (SCNT) and in vitro fertilization (IVF) were significantly higher in the
      5% KSR supplemented group than in the unsupplemented control group and more
      similar to those of the 10% pFF supplemented group. Moreover, the intensity of
      GDF9, BMP15, ROS, GSH, BODIPY-LD, BODIPY-FA, and BODIPY-ATP staining showed
      similar values between 5% KSR and 10% pFF, which have significant difference with
      control group. Most of the gene expression related to lipid metabolism with both
      supplements exhibited similar patterns. In conclusion, 5% KSR upregulated lipid
      metabolism and thereby provides an essential energy source to sustain and improve
      oocyte quality and subsequent embryo development after PA, SCNT, and IVF. These
      indications support the idea that KSR used as a defined serum supplement for
      oocyte IVM might be universally used in other species.

PMID- 29345311
TI  - Calcium-sensing receptor activates the NLRP3 inflammasome in LS14 preadipocytes
      mediated by ERK1/2 signaling.
AB  - The study of the mechanisms that trigger inflammation in adipose tissue is key to
      understanding and preventing the cardiometabolic consequences of obesity. We have
      proposed a model where activation of the G protein-coupled calcium sensing
      receptor (CaSR) leads to inflammation and dysfunction in adipose cells. Upon
      activation, CaSR can mediate the expression and secretion of proinflammatory
      factors in human preadipocytes, adipocytes, and adipose tissue explants. One
      possible pathway involved in CaSR-induced inflammation is the activation of the
      NLR family, pyrin domain-containing 3 (NLRP3) inflammasome, that promotes
      maturation and secretion of interleukin (IL)-1beta. The present work aimed to
      study whether CaSR mediates the activation of NLRP3 inflammasome in the human
      adipose cell model LS14. We assessed NLRP3 inflammasome priming and assembly
      after cinacalcet-induced CaSR activation and evaluated if this activation is
      mediated by downstream ERK1/2 signaling in LS14 preadipocytes. Exposure to 2 MUM
      cinacalcet elevated mRNA expression of NLRP3, CASP-1, and IL-1beta, as well as an
      increase in pro-IL-1beta protein. In addition, CaSR activation triggered NLRP3
      inflammasome assembly, as evidenced by a 25% increase in caspase-1 activity and
      63% IL-1beta secretion. CaSR silencing (siRNA) abolished the effect. Upstream ERK
      pathway inhibition decreased cinacalcet-dependent activation of NLRP3
      inflammasome. We propose CaSR-dependent NLRP3 inflammasome activation in
      preadipocytes through ERK signaling as a novel mechanism for the development of
      adipose dysfunction, that may favor the cardiovascular and metabolic consequences
      of obesity. To the best of our knowledge, this is the first report linking the
      inflammatory effect of CaSR to NLRP3 inflammasome induction in adipose cells.

PMID- 29345312
TI  - Phylogenetic patterns of trait and trait plasticity evolution: Insights from
      amphibian embryos.
AB  - Environmental variation favors the evolution of phenotypic plasticity. For many
      species, we understand the costs and benefits of different phenotypes, but we
      lack a broad understanding of how plastic traits evolve across large clades.
      Using identical experiments conducted across North America, we examined prey
      responses to predator cues. We quantified five life-history traits and the
      magnitude of their plasticity for 23 amphibian species/populations (spanning
      three families and five genera) when exposed to no cues, crushed-egg cues, and
      predatory crayfish cues. Embryonic responses varied considerably among species
      and phylogenetic signal was common among the traits, whereas phylogenetic signal
      was rare for trait plasticities. Among trait-evolution models, the Ornstein
      Uhlenbeck (OU) model provided the best fit or was essentially tied with Brownian
      motion. Using the best fitting model, evolutionary rates for plasticities were
      higher than traits for three life-history traits and lower for two. These data
      suggest that the evolution of life-history traits in amphibian embryos is more
      constrained by a species' position in the phylogeny than is the evolution of life
      history plasticities. The fact that an OU model of trait evolution was often a
      good fit to patterns of trait variation may indicate adaptive optima for traits
      and their plasticities.

PMID- 29345313
TI  - A microfluidic chip with a staircase pH gradient generator, a packed column and a
      fraction collector for chromatofocusing of proteins.
AB  - A microfluidic device for pH gradient chromatofocusing is presented, which
      performs creation of a micro-column, pH gradient generation, and fraction
      collection in a single device. Using a sieve micro-valve, anion exchange
      particles were packed into a microchannel in order to realize a solid-phase
      absorption column. To fractionate proteins according to their isoelectric points,
      elution buffer solutions with a stepwise pH gradient were prepared in 16 parallel
      mixing reactors and flowed through the micro-column, wherein a protein mixture
      was previously loaded. The volume of the column is only 20 nL, hence it allows
      extremely low sample consumption and fast analysis compared with a conventional
      system. We demonstrated separation of two proteins, albumin-fluorescein
      isothiocyanate conjugate (FITC-BSA) and R-Phycoerythrin (R-PE), by using a
      microcolumn of commercial charged polymeric particles (Source 15Q). The
      microfluidic device can be used as a rapid diagnostic tool to analyse crude
      mixtures of proteins or nucleic acids and determine adsorption/desorption
      characteristics of various biochemical products, which can be helpful for
      scientific fundamental understanding as well as instrumental in various
      industrial applications, especially in early stage screening and process
      development.

PMID- 29345314
TI  - The prevalence and distribution of sheep scab in Wales: a farmer questionnaire
      survey.
AB  - Outbreaks of ovine psoroptic mange in the U.K. have increased 100-fold since its
      deregulation in 1992, with the highest prevalence in Wales, a region of high
      sheep density. A cross-sectional, retrospective, questionnaire-based survey of
      7500 members of the association of Welsh lamb and beef farmers [Welsh Lamb and
      Beef Producers Ltd (WLBP)] was used to investigate the prevalence and
      distribution of sheep scab in this region in 2015. The survey was completed by
      14.0% (n = 972) of potential respondents. Scab outbreaks were reported on 15.8%
      (n = 154) of farms in 2015. However, 29.0% (n = 282) of farms reported at least
      one scab outbreak and 2.4% (n = 23) of farms had experienced between six and 10
      outbreaks in the previous 10 years. Most outbreaks occurred during September
      January (83.0%, n = 150), and were clustered around Brecon (mid-Wales) and Bangor
      (North Wales). Farmers who used common grazing were significantly more likely to
      report scab outbreaks in the previous 10 years than farmers who did not. No
      quarantine procedures for sheep bought in were used by 29.0% (n = 262) of
      farmers. Future research should be directed towards the development of localized
      management programmes, with a particular focus on areas of common grazing.

PMID- 29345315
TI  - Chlorophyll fluorescence induction and relaxation system for the continuous
      monitoring of photosynthetic capacity in photobioreactors.
AB  - The development of high-performance photobioreactors equipped with automatic
      systems for non-invasive real-time monitoring of cultivation conditions and
      photosynthetic parameters is a challenge in algae biotechnology. Therefore, we
      developed a chlorophyll (Chl) fluorescence measuring system for the online
      recording of the light-induced fluorescence rise and the dark relaxation of the
      flash-induced fluorescence yield (Qa- - re-oxidation kinetics) in
      photobioreactors. This system provides automatic measurements in a broad range of
      Chl concentrations at high frequency of gas-tight sampling, and advanced data
      analysis. The performance of this new technique was tested on the green
      microalgae Chlamydomonas reinhardtii subjected to a sulfur deficiency stress and
      to long-term dark anaerobic conditions. More than thousand fluorescence kinetic
      curves were recorded and analyzed during aerobic and anaerobic stages of
      incubation. Lifetime and amplitude values of kinetic components were determined,
      and their dynamics plotted on heatmaps. Out of these data, stress-sensitive
      kinetic parameters were specified. This implemented apparatus can therefore be
      useful for the continuous real-time monitoring of algal photosynthesis in
      photobioreactors.

PMID- 29345316
TI  - Histopathological findings in pregnancy associated cutaneous hyperpigmentation.
AB  - Hyperpigmentation in pregnancy is a common phenomenon, experienced to some degree
      by up to 90% of pregnant women. It mainly involves sun-exposed areas, but it can
      extend to non-exposed zones. Cases with extensive hyperpigmentation are rarely
      reported. In this paper, we describe the case of a 30-year-old phototype V woman
      in her 37th week of pregnancy, who presented with brownish hyperpigmentation of
      the skin in extensive areas, including both axillae, the abdomen and the lowest
      part of the back. In the abdomen, there was a reinforcement of the
      hyperpigmentation through the linea nigra and the umbilicus. The
      hyperpigmentation affected the buttocks as well and involved the intertriginous
      area between them. Histopathologic analysis showed a hyperpigmented basal layer
      of the epidermis with no melanocytic atypia or melanocytic nests. Histochemical
      staining for iron did not show any deposits. Immunohistochemical studies for HMB
      45, Melan A and SOX10 demonstrated an increased number of melanocytes. There was
      hyperpigmentation of basal layer keratinocytes. We also performed
      immunohistochemical stains for estrogen and progesterone receptors, which were
      both negative. The patient was examined 3 months after delivery, evidencing a
      significant clearing of the lesions.

PMID- 29345317
TI  - An orientation-independent DIC microscope allows high resolution imaging of
      epithelial cell migration and wound healing in a cnidarian model.
AB  - Epithelial cell dynamics can be difficult to study in intact animals or tissues.
      Here we use the medusa form of the hydrozoan Clytia hemisphaerica, which is
      covered with a monolayer of epithelial cells, to test the efficacy of an
      orientation-independent differential interference contrast microscope for in vivo
      imaging of wound healing. Orientation-independent differential interference
      contrast provides an unprecedented resolution phase image of epithelial cells
      closing a wound in a live, nontransgenic animal model. In particular, the
      orientation-independent differential interference contrast microscope equipped
      with a 40x/0.75NA objective lens and using the illumination light with wavelength
      546 nm demonstrated a resolution of 460 nm. The repair of individual cells, the
      adhesion of cells to close a gap, and the concomitant contraction of these cells
      during closure is clearly visualized.

PMID- 29345318
TI  - Retrospective study on midfacial advancement in syndromic craniosynostosis: case
      series.
AB  - AIMS: The aim of this study was to evaluate elastic distraction surgical
      procedures performed on patients with syndromic craniosynostosis using
      cephalometric analyses. METHODS: Eleven patients who underwent surgical midfacial
      advancement were divided into three groups: G1 - monobloc frontofacial; G2 - Le
      Fort III; and G3 - high-level Le Fort I. The cephalometric analyses were manually
      created through cephalometric radiographs of each patient: T1 - preoperative; T2 
      6 months postoperatively; and T3 - 12 months postoperatively. The cephalometric
      landmark points were A and O. The distances between preoperative and
      postoperative tracings were measured. RESULTS: Point A advanced with no
      significant relapse 12 months after surgery. Point O advanced with a significant
      relapse rate of 28.5% postoperatively (p = 0.019). The vertical movement of
      points A and O increased by 40.6% (p = 0.033) and 38.8% (p = 0.032),
      respectively. There were no significant statistical differences between the
      assessed surgical techniques and syndromes with regard to midfacial advancement.
      CONCLUSION: Point O has presented statistically significant relapse only in
      horizontal movement after 12 months. The cephalometric analysis performed in the
      present study only suggested no differences between the studied surgical
      techniques and syndromes with regard to midfacial advancement in syndromic
      craniosynostosis.

PMID- 29345320
TI  - Dental local anesthesia for patients with pseudocholinesterase deficiency.

PMID- 29345319
TI  - Endothelial cells enhance adipose mesenchymal stromal cell-mediated matrix
      contraction via ALK receptors and reduced follistatin: Potential role of
      endothelial cells in skin fibrosis.
AB  - Abnormal cutaneous wound healing can lead to formation of fibrotic hypertrophic
      scars. Although several clinical risk factors have been described, the cross-talk
      between different cell types resulting in hypertrophic scar formation is still
      poorly understood. The aim of this in vitro study was to investigate whether
      endothelial cells (EC) may play a role in skin fibrosis, for example,
      hypertrophic scar formation after full-thickness skin trauma. Using a
      collagen/elastin matrix, we developed an in vitro fibrosis model to study the
      interaction between EC and dermal fibroblasts or adipose tissue-derived
      mesenchymal stromal cells (ASC). Tissue equivalents containing dermal fibroblasts
      and EC displayed a normal phenotype. In contrast, tissue equivalents containing
      ASC and EC displayed a fibrotic phenotype indicated by contraction of the matrix,
      higher gene expression of ACTA2, COL1A, COL3A, and less secretion of follistatin.
      The contraction was in part mediated via the TGF-beta pathway, as both inhibition
      of the ALK4/5/7 receptors and the addition of recombinant follistatin resulted in
      decreased matrix contraction (75 +/- 11% and 24 +/- 8%, respectively). In
      conclusion, our study shows that EC may play a critical role in fibrotic events,
      as seen in hypertrophic scars, by stimulating ASC-mediated matrix contraction via
      regulation of fibrosis-related proteins.

PMID- 29345321
TI  - Good Practices for Observational Studies of Maternal Weight and Weight Gain in
      Pregnancy.

PMID- 29345322
TI  - Effect of substrate stiffness on hepatocyte migration and cellular Young's
      modulus.
AB  - Hepatic fibrosis progress accompanied by an unbalanced extracellular matrix (ECM)
      degradation and deposition leads to an increased tissue stiffness. Hepatocytes
      interplay with all intrahepatic cell populations inside the liver. However, how
      hepatocytes migration and cellular Young's modulus influenced by the substrate
      stiffness are not well understood. Here, we established a stiffness-controllable
      in vitro cell culture model by using a polyvinyl alcohol (PVA) hydrogel that
      mimicked the same physical stiffness as a fibrotic liver. Three levels of
      stiffness were used in our experiment that corresponded to the stiffness levels
      found in normal liver tissue (4.5 kPa), the early (19 kPa) and late stages (37
      kPa) of fibrotic liver tissues. Cytoskeleton of hepatocyte was influenced by
      substrate stiffness. Soft substrate promoted the cellular migration and
      directionality. The cellular Young's modulus firstly increased and then decreased
      with increasing substrate stiffness. Integrin-beta1 and beta-catenin expression
      on cytomembrane were up-regulated and down-regulated with the increase of
      substrate stiffness, respectively. Our data not only suggested that hepatocytes
      were sensitive to substrate stiffness, but also suggested that there may be a
      potential relationship among substrate stiffness, cellular Young's modulus and
      the dynamic balance of integrin-beta1 and beta-catenin pathways. These results
      may provide us a new insight in mechanism investigation of mechano-dependent
      diseases, especially like fibrosis related diseases.

PMID- 29345323
TI  - Vernalization can regulate flowering time through microRNA mechanism in Brassica
      rapa.
AB  - Vernalization is an important process that regulates the floral transition in
      plants. MicroRNAs (miRNAs) are endogenous non-coding small RNA (sRNA) molecules
      that function in plant growth and development. Despite that miRNAs related to
      flowering have previously been characterized, their roles in response to
      vernalization in pak-choi (Brassica rapa ssp. chinensis) has never been studied.
      Here, two sRNA libraries from B. rapa leaves (vernalized and non-vernalized
      plants) were constructed and sequenced. Two hundred eight known and 535 novel
      miRNAs were obtained, of which 20 known and 66 new miRNAs were significantly
      differentially expressed and considered as vernalization-related miRNAs. The
      corresponding targets were predicted on the basic of sequence homology search. In
      addition, 11 miRNAs and eight targets were selected for real-time quantitative
      PCR to confirm their expression profiles. Functional annotation of targets using
      gene ontology and Kyoto encyclopedia of genes and genomes results suggested that
      most targets were significantly enriched in the hormone signaling pathway.
      Moreover, a decreased indole-3-acetic acid (IAA) and an increased GA3 hormone
      were detected after vernalization, indicating that the IAA and GA3 might response
      to vernalization. These results indicated that vernalization regulates flowering
      through microRNA mechanism by affecting endogenous hormone level in B. rapa. This
      study provides useful insights of promising miRNAs candidates involved in
      vernalization in B. rapa, and facilitates further investigation of the miRNA
      mediated molecular mechanisms of vernalization in B. rapa.

PMID- 29345324
TI  - Autocrine signals increase ovine mesenchymal stem cells migration through
      Aquaporin-1 and CXCR4 overexpression.
AB  - Sheep is a relevant large animal model that is frequently used to test innovative
      tissue engineering (TE) approaches especially for bone reconstruction.
      Mesenchymal stem cells (MSCs) are used in TE applications because they represent
      key component of adult tissue repair. Importantly, MSCs from different species
      show similar characteristics, which facilitated their application in
      translational studies using animal models. Nowadays, many researches are focusing
      on the use of ovine mesenchymal stem cells (oMSCs) in orthopedic preclinical
      settings for regenerative medicine purposes. Therefore, there is a need to
      amplify our knowledge on the mechanisms underlying the behaviour of these cells.
      Recently, several studies have shown that MSC function is largely dependent on
      factors that MSCs release in the environment, as well as, in conditioned medium
      (CM). It has been demonstrated that MSCs through autocrine and paracrine signals
      are able to stimulate proliferation, migration, and differentiation of different
      type of cells including themselves. In this study, we investigated the effects of
      the CM produced by oMSCs on oMSCs themselves and we explored the signal pathways
      involved. We observed that CM caused an enhancement of oMSC migration.
      Furthermore, we found that CM increased levels of two membrane proteins involved
      in cell migration, Aquaporin 1 (AQP1), and C-X-C chemokine receptor type 4
      (CXCR4), and activated Akt and Erk intracellular signal pathways. In conclusion,
      taken together our results suggest the high potential of autologous CM as a
      promising tool to modulate behaviour of MSCs thus improving their use in
      therapeutically approaches.

PMID- 29345325
TI  - A new retrograde transillumination technique for videolaryngoscopic tracheal
      intubation.
AB  - This single-centre, prospective trial was designed to assess the efficacy of a
      new retrograde transillumination device called the 'Infrared Red Intubation
      System' (IRRIS) to aid videolaryngoscopic tracheal intubation. We included 40
      adult patients, who were undergoing elective urological surgery under general
      anaesthesia. We assessed the ability to differentiate the transilluminated
      glottis from other structures and found a median (IQR [range]) larynx recognition
      time of 8 (5-14 [3-28]) s. The difference in laryngeal visibility on the screen
      between the deactivated vs. activated device expressed on a visual analogue scale
      was significant (6 (4-7 [2-10]) vs. 10 (8-10 [4-10]); p < 0.001). The number of
      laryngoscope insertions was 1 (1-2 [1-3]) and the device showed high values on a
      visual analogue scale ranging from 0 (lowest score) to 10 (highest score) for
      helpfulness (6 (5-7 [2-10])), credibility (10 (8-10 [5-10])) and ease of use (10
      (9-10 [8-10])). Tracheal intubation with the system lasted 26 (16-32 [6-89]) s.
      No alternative technique of securing the airway was necessary. The lowest SpO2
      during intubation was 98 (97-99 [91-100])%. We conclude that this method of
      retrograde transillumination can assist videolaryngoscopy.

PMID- 29345326
TI  - Live-Animal Imaging of Renal Function by Multiphoton Microscopy.
AB  - Intravital microscopy, microscopy of living animals, is a powerful research
      technique that combines the resolution and sensitivity found in microscopic
      studies of cultured cells with the relevance and systemic influences of cells in
      the context of the intact animal. The power of intravital microscopy has recently
      been extended with the development of multiphoton fluorescence microscopy systems
      capable of collecting optical sections from deep within the kidney at subcellular
      resolution, supporting high-resolution characterizations of the structure and
      function of glomeruli, tubules, and vasculature in the living kidney. Fluorescent
      probes are administered to an anesthetized, surgically prepared animal, followed
      by image acquisition for up to 3 hr. Images are transferred via a high-speed
      network to specialized computer systems for digital image analysis. This general
      approach can be used with different combinations of fluorescent probes to
      evaluate processes such as glomerular permeability, proximal tubule endocytosis,
      microvascular flow, vascular permeability, mitochondrial function, and cellular
      apoptosis/necrosis. (c) 2018 by John Wiley & Sons, Inc.

PMID- 29345327
TI  - Basics of Digital Microscopy.
AB  - Modern digital microscopy combines the equipment of classical light microscopy
      with a computerized imaging system. The technique comprises image formation by
      optics, image registration by a camera, and saving of image data in a computer
      file. This chapter describes limitations that are particular to each of these
      processes, including optical resolution, efficiency of image registration,
      characteristics of image file formats, and data management. Further suggestions
      are given which serve, in turn, to help construct a set of guidelines aimed at
      optimization of digital microscopic imaging. (c) 2018 by John Wiley & Sons, Inc.

PMID- 29345328
TI  - Lasers for Flow Cytometry: Current and Future Trends.
AB  - Lasers are the principal light sources for flow cytometers. Virtually all
      cytometers are equipped with at least one (and often many more) lasers. This unit
      covers the various types of lasers available and the qualities that make them
      suitable or unsuitable for use in flow cytometers. Also included is a discussion
      of future directions, particularly in the area of tunable laser development.
      Practical tips are provided for building multilaser cytometer systems. (c) 2018
      by John Wiley & Sons, Inc.

PMID- 29345329
TI  - Generating Quantitative Cell Identity Labels with Marker Enrichment Modeling
      (MEM).
AB  - Multiplexed single-cell experimental techniques like mass cytometry measure 40 or
      more features and enable deep characterization of well-known and novel cell
      populations. However, traditional data analysis techniques rely extensively on
      human experts or prior knowledge, and novel machine learning algorithms may
      generate unexpected population groupings. Marker enrichment modeling (MEM)
      creates quantitative identity labels based on features enriched in a population
      relative to a reference. While developed for cell type analysis, MEM labels can
      be generated for a wide range of multidimensional data types, and MEM works
      effectively with output from expert analysis and diverse machine learning
      algorithms. MEM is implemented as an R package and includes three steps: (1)
      calculation of MEM values that quantify each feature's relative enrichment in the
      population, (2) reporting of MEM labels as a heatmap or as a text label, and (3)
      quantification of MEM label similarity between populations. The protocols here
      show MEM analysis using datasets from immunology and oncology. These MEM
      implementations provide a way to characterize population identity and novelty in
      the context of computational and expert analyses. (c) 2018 by John Wiley & Sons,
      Inc.

PMID- 29345332
TI  - Environmental electron microscopy: materials in their real live in gas or liquid.

PMID- 29345330
TI  - Non-Parametric Comparison of Single Parameter Histograms.
AB  - A number of methods have been developed to compare single parameter histograms.
      Some perform a channel-by-channel analysis and others give a single statistic
      about how the histograms may or may not differ. If they do differ, then the
      significance of the difference or confidence limit is usually provided. The
      specific location(s) for the greatest deviations may also be given. Some are more
      effective at resolving severely overlapping populations and others work poorly
      when there is any significant overlap. Each method makes certain assumptions
      about the data. It is important to understand the assumptions being made and to
      understand the limitations of each method. It is essential to know how to
      identify when a comparison method will work for a given set of histograms. This
      unit explores the different methods, and provides a guide for the reader to
      choose the most appropriate method(s) to use for a specific data set(s). (c) 2018
      by John Wiley & Sons, Inc.

PMID- 29345333
TI  - Effects and mechanism of puerarin on the human retinoblastoma cells.
AB  - Puerarin is an isoflavonoid that is extracted from Kudzu root and is considered
      to have an anti-tumor effect. In the present study, the effects of puerarin on
      human retinoblastoma (RB) cells and the related pathways was determined. The
      retinoblastoma RB cell lines were used in this study. Cell viability and colony
      formation capacity were measured by MTT and colony formation assays. Cell cycle
      was determined by flow cytometry. Cell migration and invasion were examined by
      Transwell assay. The expression of cell cycle, EMT, and MAPK/ERK signal pathway
      related proteins were detected by western blot following puerarin treatment. The
      results revealed that cell viability and proliferation of RB cells treated with
      puerarin were significantly lower in RB cells compared to the control group.
      Puerarin significantly decreased the proportion of cells during S phase which was
      accompanied with increase in cells at G0/1 and G2 phases. Moreover, puerarin
      suppressed cell migration, invasion and up-regulated E-Cadherin expression as
      well as down-regulated Vimentin and alpha-SMA expression. Furthermore, puerarin
      treatment suppressed the expression of p-MEK and p-ERK in RB cells. Our findings
      suggest that puerarin contributes to in the treatment of RB and other malignant
      tumors.

PMID- 29345334
TI  - Roles of the three Mycobacterium smegmatis katG genes for peroxide detoxification
      and isoniazid susceptibility.
AB  - Three different katG sequences (katGI, katGII and katGIII) were identified in the
      Mycobacterium smegmatis genome. The contributions of the three katG genes to
      survival of the bacterium were examined by constructing disruptants of these
      three genes. The katGIII sequence did not produce a functional catalase
      peroxidase. Analyses of peroxidase activity and mRNA expression revealed that in
      wild type M. smegmatis, expression dominance between KatGI and KatGII was
      switched in the exponential and stationary growth phases. Susceptibility of the
      M. smegmatis gene disruptants to hydrogen peroxide (H2 O2 ) was tested in two
      growth phases. In the exponential phase, the katGI-null strain was more
      susceptible to H2 O2 than the katGII-null strain, indicating that KatGI plays a
      more important role in survival than KatGII in this growth phase. In contrast, in
      the stationary phase, growth of the katGII-null strain was inhibited at lower
      concentrations of H2 O2 . These results suggest that M. smegmatis has two types
      of catalase-peroxidases, expressions of which are controlled under different gene
      regulatory systems. Isoniazid (INH) susceptibilities of the katG-null strains
      were also examined and it was found that katGI is a major determinant of M.
      smegmatis susceptibility to INH.

PMID- 29345335
TI  - Heat shock protein 70 modulates neural progenitor cells dynamics in human
      neuroblastoma SH-SY5Y cells exposed to high glucose content.
AB  - In the current experiment, detrimental effects of high glucose condition were
      investigated on human neuroblastoma cells. Human neuroblastoma cell line SH-SY5Y
      were exposed to 5, 40, and 70 mM glucose over a period of 72 h. Survival rate and
      the proliferation of cells were analyzed by MTT and BrdU incorporation assays.
      Apoptosis was studied by the assays of flow cytometry and PCR array. In order to
      investigate the trans-differentiation capacity of the cell into mature neurons,
      we used immunofluorescence imaging to follow NeuN protein level. The
      transcription level of HSP70 was shown by real-time PCR analysis. MMP-2 and -9
      activities were shown by gelatin Zymography. According to data from MTT and BrdU
      incorporation assay, 70 mM glucose reduced cell viability and proliferation rate
      as compared to control (5 mM glucose) and cells treated with 40 mM glucose (P <
      0.05). Cell exposure to 70 mM glucose had potential to induced apoptosis after 72
      h (P < 0.05). Our results also demonstrated the sensitivity of SH-SY5Y cells to
      detrimental effects of high glucose condition during trans-differentiation into
      mature neuron-like cells. Real-time PCR analysis confirmed the expression of
      HSP70 in cells under high content glucose levels, demonstrating the possible cell
      compensatory response to an insulting condition (pcontrol vs 70 mM group  <0.05).
      Both MMP-2 and -9 activities were reduced in cells being exposed to 70 mM
      glucose. High glucose condition could abrogate the dynamics of neural progenitor
      cells. The intracellular level of HSP70 was proportional to cell damage in high
      glucose condition.

PMID- 29345336
TI  - gammadelta cells and tumor microenvironment: A helpful or a dangerous liason?
AB  - gammadelta T cells are a subset of T lymphocytes that have been implicated in
      immunosurveillance against infections and tumors. gammadelta T cells are endowed
      with antitumor activities, and hence several gammadelta T cell-based small-scale
      clinical trials have been conducted either by in vivo activation by intravenous
      administration of aminobiphosphonates or by adoptive transfer of in vitro
      expanded gammadelta T cells. Although both these strategies have yielded
      promising results, there are a number of limitations associated with each of them
      which, if overcome may help to further improve efficacy. One of the most
      important limits is the possible polarization of tumor-infiltrating gammadelta T
      cells toward different gammadelta T cells population with functional activities
      that help the progression and spread of the tumor. Here, we review the modalities
      and the possible mechanisms involved in the polarization of tumor-infiltrating
      gammadelta T cells upon interaction with several components of the tumor
      microenvironment and discuss their implications for the manipulation of
      gammadelta T cells in cancer immunotherapy.

PMID- 29345337
TI  - Effects of Benzoapyrene on migration and invasion of lung cancer cells
      functioning by TNF-alpha.
AB  - In this study, we attempted to find out the underlying mechanism of Benzoapyrene
      and metastasis of lung cancer cells. We also did experiments to testify the
      connection between BaP and its potential target, TNF-alpha. Cell median lethal
      dose (IC50 ) of both cells was measured by crystal violet method. Quantitative
      real-time reverse transcription PCR (qRT-PCR) and Western blot were employed to
      detect the expression of TNF-alpha. Wound healing assay and transwell assay were
      utilized to testify the impacts of BaP and TNF-alpha on the metastasis of lung
      cancer cells. Cell death rate was elevated with the increase of BaP
      concentration. BaP increased the number of metastatic cells of lung cancer. The
      expressions of TNF-alpha pathway-associated protein (TNF-alpha, NF-kB [P65],
      Caspase3, and Caspase8) were enhanced by overexpressed BaP. TNF-alpha shRNA
      suppressed the positive effects of BaP on migration and invasion of lung cancer
      cells. Our study validated the positive effects of BaP on the metastasis of lung
      cancer cells. We also revealed the instrumental role of TNF-alpha in helping the
      development of lung cancer cells induced by BaP.

PMID- 29345338
TI  - MIAT lncRNA is overexpressed in breast cancer and its inhibition triggers
      senescence and G1 arrest in MCF7 cell line.
AB  - Long non-coding RNAs are known as key regulators in the progression and
      metastasis of breast cancer. MIAT originally has been considered as an lncRNA to
      be associated with a susceptibility to myocardial infarction. Here, we have
      detected the expression of MIAT in different cancer cells and a series of breast
      tumor tissue. MIAT expression was much higher in high-grade tumors compared to
      low-grade ones. Unlike P53 positive tumors, MIAT expression was upregulated in
      ER, PR, Her2 positive tumor tissues. Knockdown MIAT suppressed breast cancer cell
      proliferation and caused G1 arrest in cell cycle. Furthermore, downregulation of
      MIAT promoted apoptosis and significantly decreased migration of breast cancer
      cells. An increase in the expression of mir-302, mir-150, and a decrease in the
      expression of mir-29c were detected following MIAT silencing. More importantly,
      knockdown MIAT significantly elevated the expression of p16Ink4A and Cox2, which
      commitment cellular senescence in breast cancer cells. Altogether, our results
      suggest that MIAT involved in breast cancer progression and could be candidate as
      a novel tumor marker for diagnosis and treatment of breast cancer.

PMID- 29345339
TI  - The role of Cdk5-mediated Drp1 phosphorylation in Abeta1-42 induced mitochondrial
      fission and neuronal apoptosis.
AB  - Alzheimer's disease, one of the most common neurodegenerative diseases, is
      pathologically characterized by Amyloid beta containing plaques and
      neurofibrillary tangles. Amyloid beta (Abeta) induces neuronal apoptosis through
      the intracellular Ca2+ increase, subsequent hyperactivation of cyclin-dependent
      kinase 5 (Cdk5) and mitochondrial abnormality. Recently, Cdk5 was identified as
      an upstream regulator of mitochondrial fission during neuronal apoptosis, but the
      underlying mechanism remains unclear. Here, in vitro phosphorylation assays
      showed that Cdk5 could phosphorylate the recombinant Drp1 at Serine 579. Abeta1
      42 stimulation increased the phosphorylation level of Drp1 at Serine 579 in mouse
      cortical neurons. Cdk5 inhibitor roscovitine and knockdown of Cdk5 by a
      lentiviral vector expressing shRNA targeting Cdk5 (Lenti-Cdk5-shRNA) efficiently
      prevented Abeta1-42 induced Drp1 phosphorylation in neurons. In addition, Abeta1
      42 stimulation induced markedly mitochondrial fission in neurons. Roscovitine,
      Lenti-Cdk5-shRNA and expression of phospho-defect mutatant GFP-Drp1-S579A in
      neurons attenuated Abeta1-42 induced mitochondrial fission, whereas expression of
      phospho-mimetic mutant GFP-Drp1-S579D alone resulted in mitochondiral fission
      similar to Abeta1-42 stimulation. Moreover, Roscovitine and Lenti-Cdk5-shRNA
      suppressed the cleavage of caspase-3 and protected neurons against Abeta1-42
      induced neuronal apoptosis.Thus, our data indicate that Drp1 is a direct target
      of Cdk5, and Cdk5-mediated phosphorylation of Drp1 at Serine 579 regulates Abeta1
      42 induced mitochondrial fission and neuronal toxicity.

PMID- 29345340
TI  - Berberine demonstrates anti-inflammatory properties in Helicobacter pylori
      infected mice with chronic gastritis by attenuating the Th17 response triggered
      by the B cell-activating factor.
AB  - Berberine (BBR) is an isoquinoline alkaloid derived from various medicinal herbs.
      Previous studies have suggested that BBR exerts antimicrobial, antitumor, and
      antidiabetic effects and can be used to treat Helicobacter pylori-induced chronic
      gastritis. However, the exact mechanism by which BBR inhibits H. pylori infection
      is not fully understood. We investigated the anti-inflammatory properties and
      potential mechanism of BBR in H. pylori-infected mice with chronic gastritis. We
      found that BBR can suppress the expression of pro-inflammatory genes IL-6, TGF
      beta, and IL-1beta and upregulate anti-inflammatory gene IL-10 expression in the
      mucosa and RAW 264.7 macrophages. Exposure to BBR also reduced the expression and
      accumulation of IL-17 in the mucosa and CD4+ T cells activated by anti-CD3 and
      anti-CD28, and it decreased the frequency of IL-17-producing CD4+ T cells. B cell
      activating factor (BAFF) production was inhibited by BBR and by cultured
      dendritic and CD4+ T cells. Furthermore, we demonstrated that BAFF can trigger
      the Th17 response by promoting the production of pro-Th17 cytokines IL-6, TGF
      beta, and IL-1beta, which are strongly associated with the anti-inflammatory role
      of BBR in chronic gastritis caused by H. pylori. In conclusion, we determined
      that BBR has anti-inflammatory effects on H. pylori-induced chronic gastritis by
      attenuating the BAFF-triggered Th17 response.

PMID- 29345341
TI  - Novel insights into FAS defects underlying autoimmune lymphoproliferative
      syndrome revealed by studies in consanguineous patients.
AB  - Autoimmune lymphoproliferative syndrome (ALPS) is a primary immunodeficiency
      disease due to impaired Fas-Fas ligand apoptotic pathway. It is characterized by
      chronic nonmalignant, noninfectious lymphadenopathy and/or splenomegaly
      associated with autoimmune manifestations primarily directed against blood cells.
      Herein, we review the heterogeneous ALPS molecular bases and discuss recent
      findings revealed by the study of consanguineous patients. Indeed, this peculiar
      genetic background favored the identification of a novel form of AR ALPS-FAS
      associated with normal or residual protein expression, expanding the spectrum of
      ALPS types. In addition, rare mutational mechanisms underlying the splicing
      defects of FAS exon 6 have been identified in AR ALPS-FAS with lack of protein
      expression. These findings will help decipher critical regions required for the
      tight regulation of FAS exon 6 splicing. We also discuss the genotype-phenotype
      correlation and disease severity in AR ALPS-FAS. Altogether, the study of ALPS
      molecular bases in endogamous populations helps to better classify the disease
      subgroups and to unravel the Fas pathway functioning.

PMID- 29345342
TI  - Frontline Science: High fat diet and leptin promote tumor progression by inducing
      myeloid-derived suppressor cells.
AB  - Obesity is a risk factor for cancer incidence and cancer mortality. The
      association of obesity and cancer is attributed to multiple factors, but the
      tightest linkage is with the chronic, low-grade inflammation that accompanies
      obesity. Myeloid-derived suppressor cells (MDSC) are known facilitators of cancer
      progression that act by suppressing the activation and function of tumor-reactive
      T cells. Because MDSC quantity and function are driven by chronic inflammation,
      we hypothesized that MDSC may accumulate in obese individuals and facilitate
      tumor growth by suppressing antitumor immunity. To test this hypothesis, tumor
      bearing mice on a high fat or low fat diet (HFD or LFD) were assessed for tumor
      progression and the metabolic dysfunction associated with obesity. HFD enhanced
      the accumulation of MDSC, and the resulting MDSC had both beneficial and
      detrimental effects. HFD-induced MDSC protected mice against diet-induced
      metabolic dysfunction and reduced HFD-associated inflammation, but also increased
      the accumulation of fat, enhanced tumor progression, and spontaneous metastasis
      and reduced survival time. HFD-induced MDSC facilitated tumor growth by limiting
      the activation of tumor-reactive CD8+ T cells. Leptin, an adipokine that
      regulates appetite satiety and is overexpressed in obesity, undergoes crosstalk
      with MDSC in which leptin drives the accumulation of MDSC while MDSC down
      regulate the production of leptin. Collectively, these studies demonstrate that
      although MDSC protect against some metabolic dysfunction associated with HFD they
      enhance tumor growth in HFD mice and that leptin is a key regulator linking HFD,
      chronic inflammation, immune suppression, and tumor progression.

PMID- 29345343
TI  - Mycobacterium tuberculosis: Rewiring host cell signaling to promote infection.
AB  - The ability of Mycobacterium tuberculosis to cause disease hinges upon
      successfully thwarting the innate defenses of the macrophage host cell. The
      pathogen's trump card is its armory of virulence factors that throw normal host
      cell signaling into disarray. This process of subverting the macrophage begins
      upon entry into the cell, when M. tuberculosis actively inhibits the fusion of
      the bacilli-laden phagosomes with lysosomes. The pathogen then modulates an array
      of host signal transduction pathways, which dampens the macrophage's host
      protective cytokine response, while simultaneously adapting host cell metabolism
      to stimulate lipid body accumulation. Mycobacterium tuberculosis also renovates
      the surface of its innate host cells by altering the expression of key molecules
      required for full activation of the adaptive immune response. Finally, the
      pathogen coordinates its exit from the host cell by shifting the balance from the
      host-protective apoptotic cell death program toward a lytic form of host cell
      death. Thus, M. tuberculosis exploits its extensive repertoire of virulence
      factors in order to orchestrate the infection process to facilitate its growth,
      dissemination, and entry into latency. This review offers critical insights into
      the most recent advances in our knowledge of how M. tuberculosis manipulates host
      cell signaling. An appreciation of such interactions between the pathogen and
      host is critical for guiding novel therapies and understanding the factors that
      lead to the development of active disease in only a subset of exposed
      individuals.

PMID- 29345345
TI  - Autophagy inhibition promotes phagocytosis of macrophage and protects mice from
      methicillin-resistant staphylococcus aureus pneumonia.
AB  - The present study is to investigate the effect of autophagy in macrophages and
      the protection of mouse models against MRSA invasion, which provide new potential
      therapeutic direction for lung infection. The effect of ST239 in macrophages were
      analyzed by Western blot. The immunofluorescence was used to observe the
      influence of autophagy inhibitor 3-MA in macrophages. Then we established MRSA
      mice model and the models were divided into different groups of drugs. The effect
      of autophagy in macrophage with MRSA and the changes of lung pathological in the
      mouse model was analyzed by flow cytometry and immunohistochemistry. The ability
      of phagocytic decreases when ST239 infected the macrophages. And the autophagy
      related genes Beclin-1, LC3-I, and LC3-II protein expression significantly
      increased. GFP-LC3 immunostaining showed that GFP-LC3 was significantly over
      expressed in ST239-infected macrophages. Then we found the autophagy inhibitors 3
      MA could make the expression of autophagy-related genes Beclin-1, LC3-I, and LC3
      II decreased, the number of ST239 decreased, and the ability of macrophages
      phagocytosed MRSA increasing. In the mouse model we performed the same assay, the
      results showed that the percentage of macrophages in the mouse model treated with
      3-MA was increased compared to the ST239 mouse model and that the number of
      bacteria in right lung significantly reduced. Lung cells treated with3-MA
      significantly improved the lesion of ST239 lung cell disease. Inhibition of
      autophagy can increase the ability of macrophages phagocytosed MRSA, and it is a
      suitable target for preventing or treating MRSA infection.

PMID- 29345346
TI  - Galectin-3 type-C self-association on neutrophil surfaces; The carbohydrate
      recognition domain regulates cell function.
AB  - Galectin-3 is an endogenous beta-galactoside-binding lectin comprising a
      carbohydrate recognition domain (CRD) linked to a collagen-like N-domain. Both
      domains are required for galectin-3 to induce cellular effects; a C-terminal
      fragment of galectin-3, galectin-3C, containing the CRD but lacking the N-domain,
      binds cell surface glycoconjugates but does not induce cellular effects since
      cross-linking promoted by the N-domain is thought to be required. Instead,
      galectin-3C is proposed to antagonize the effects of galectin-3 by competing for
      binding sites. The aim of this study was to investigate the effects of galectin
      3C on galectin-3 interactions with human neutrophils. Recombinant galectin-3C
      inhibited galectin-3-induced production of reactive oxygen species in primed
      neutrophils. Surprisingly, this inhibition was not due to competitive inhibition
      of galectin-3 binding to the cells. In contrast, galectin-3C potentiated galectin
      3 binding, in line with emerging evidence that galectin-3 can aggregate not only
      through the N-domain but also through the CRD. The cell surface interaction
      between galectin-3C and galectin-3 was corroborated by colocalization of
      fluorescently labeled galectin-3 and galectin-3C. Galectin-3C can be generated in
      vivo through cleavage of galectin-3 by proteases. Indeed, in circulation,
      galectin-3 and galectin-3C were both attached to the cell surface of neutrophils,
      which displayed great capacity to bind additional galectin-3 and galectin-3C. In
      conclusion, galectin-3C enhances galectin-3 binding to neutrophils by
      nonactivating type-C self-association, in parallel to inhibiting neutrophil
      activation by galectin-3 (induced by type-N self-association). This implicates
      type-C self-association as a termination system for galectin-3-induced cell
      activation, with the purpose of avoiding oxidant-dependent tissue damage.

PMID- 29345344
TI  - Differential outcomes of TLR2 engagement in inflammation-induced preterm birth.
AB  - Preterm birth (PTB) is the leading cause of neonatal mortality worldwide.
      Infection and inflammation are considered main causes of PTB. Among multiple
      pathogens, Gram-positive bacteria are commonly linked with induction of PTB.
      Although activation of innate immune responses, via TLR2 engagement, by Gram
      positive bacteria is a likely cause, whether induction of PTB depends on the
      potency of specific microbial components to induce Toll-like receptor (TLR)2
      driven inflammation has not been elucidated. Here, we show that TLR2 activation
      by synthetic lipopeptides, Pam2Cys, and Pam3Cys specifically, variably influenced
      inflammation and subsequent induction of PTB. Pam2Cys challenge, compared to
      Pam3Cys, induced PTB and promoted significantly higher expression of inflammatory
      cytokines, specifically IL-6 and IFN-beta, both in vivo and in vitro. Notably,
      antibody-mediated neutralization of IL-6 or genetic deletion of type I IFN
      receptor (IFNAR) was sufficient to protect from Pam2Cys-driven PTB and to temper
      excessive proinflammatory cytokine production. Conversely, IFN-beta or IL-6 was
      not sufficient to promote induction of PTB by Pam3Cys. In summary, our data
      implies a divergent function of TLR2-activating lipopeptides in the magnitude and
      type of ligand-driven inflammatory vigor in induction of PTB.

PMID- 29345347
TI  - Interferons and beyond: Induction of antiretroviral restriction factors.
AB  - Antiviral restriction factors are structurally and functionally diverse cellular
      proteins that play a key role in the first line of defense against viral
      pathogens. Although many cell types constitutively express restriction factors at
      low levels, their induction in response to viral exposure and replication is
      often required for potent control and repulse of the invading pathogens. It is
      well established that type I IFNs efficiently induce antiviral restriction
      factors. Accumulating evidence suggests that other types of IFN, as well as
      specific cytokines, such as IL-27, and other activators of the cell are also
      capable of enhancing the expression of restriction factors and hence to establish
      an antiviral cellular state. Agents that efficiently induce restriction factors,
      increase their activity, and/or render them resistant against viral antagonists
      without causing general inflammation and significant side effects hold some
      promise for novel therapeutic or preventive strategies. In the present review, we
      summarize some of the current knowledge on the induction of antiretroviral
      restriction factors and perspectives for therapeutic application.

PMID- 29345348
TI  - Roles of neutrophils in cancer growth and progression.
AB  - Chronic inflammation is a well-known tumor-enabling capacity, which allows
      nascent tumors to acquire all the hallmark capabilities, including the escape
      from immunosurveillance. Soluble and cellular inflammatory mediators constitute
      the complex network of the tumor microenvironment, in which tumors grow and with
      which constantly interact. Myeloid cells (e.g., tumor associated macrophages) are
      pivotal players of the tumor microenvironment and are characterized by
      plasticity, which consists of the ability to acquire distinct phenotypes in
      response to the microenvironment in which they reside. Neutrophils are emerging
      as important players of tumor microenvironment, given their heterogeneity and
      plasticity. Increasing evidence suggests a dual role for neutrophils in
      modulating tumor behavior and highlights the need for a reassessment of
      neutrophil functions in cancer initiation and progression.

PMID- 29345349
TI  - Enhanced phosphorylation of sphingosine and ceramide sustains the exuberant
      proliferation of endothelial progenitors in Kaposi sarcoma.
AB  - Endothelial colony-forming cells (ECFCs), a unique endothelial stem cell
      population, are highly increased in the blood of Kaposi sarcoma (KS) patients. KS
      derived ECFCs (KS-ECFCs) are also endowed with increased proliferative and
      vasculogenic potential, thus suggesting that they may be precursors of KS spindle
      cells. However, the mechanisms underlying the increased proliferative activity of
      KS-ECFCs remain poorly understood. Sphingosine-1-phosphate (S1P) and ceramide-1
      phosphate (C1P) are metabolically interconnected sphingoid mediators crucial to
      cell proliferation. Here, we investigated the metabolism, release, and
      proliferative effects of S1P and C1P in KS-ECFCs compared with control ECFCs (Ct
      ECFCs). Metabolic studies by cell labeling, chromatographic analyses, and digital
      autoradiography revealed that S1P and C1P biosynthesis and S1P secretion are all
      efficient processes in KS-ECFCs, more efficient in KS-ECFCs than Ct-ECFCs.
      Quantitative PCR analyses demonstrated a significantly higher ceramide kinase and
      sphingosine kinase-2 expression in KS-ECFCs. Notably, also the expression of S1P1
      and S1P3 receptors was augmented in KS-ECFCs. Accordingly, treatment with
      exogenous C1P or S1P induced a significant, concentration-dependent stimulation
      of KS-ECFC proliferation, but was almost completely ineffective in Ct-ECFCs.
      Hence, we identified C1P and S1P as autocrine/paracrine proliferative signals in
      KS-ECFCs. A better understanding of the mechanisms that enhance S1P/C1P formation
      in KS-ECFCs may yield effective therapeutic modalities.

PMID- 29345350
TI  - Activation of the sympathetic nervous system modulates neutrophil function.
AB  - Emerging evidence has revealed that noradrenaline (NA), the main neurotransmitter
      of the sympathetic nervous system (SNS), regulates a variety of immune functions
      via binding to adrenergic receptors present on immune cells. In this study, we
      examined the role of NA in the regulation of neutrophil functions. Neutrophils
      were isolated from the bone marrow of naive mice and treated with NA at various
      concentrations to assess the effect on various neutrophil functions.
      Additionally, we performed cremaster intravital microscopy to examine neutrophil
      endothelial cell interactions following NA superfusion in vivo. In a separate
      group of animals, mice were subjected to an experimental model of stroke and at 4
      and 24 h neutrophils were isolated for assessment on their ability to migrate
      toward various chemokines. Treatment of neutrophils with NA for 4 h significantly
      impaired neutrophil chemotaxis and induced an N2 neutrophil phenotype with
      reduced expression of the genes critical for cytoskeleton remodeling and
      inflammation. Prolonged NA administration promoted neutrophils to release
      myeloperoxidase and IL-6, but suppressed the production of interferon-gamma and
      IL-10, reduced neutrophil activation and phagocytosis. Superfusion of NA over the
      cremaster muscle almost completely inhibited fMLP-induced neutrophil
      adhesion/arrest and transmigration. Furthermore, using a mouse model of stroke, a
      pathological condition in which SNS activation is evident, neutrophils isolated
      from poststroke mice showed markedly reduced chemotaxis toward all of the
      chemokines tested. The findings from our study indicate that neutrophil
      chemotaxis, activation, and phagocytosis can all be negatively regulated in an NA
      dependent manner. A better understanding of the relationship between sympathetic
      activation and neutrophil function will be important for the development of
      effective antibacterial interventions.

PMID- 29345351
TI  - K313, a novel benzoxazole derivative, exhibits anti-inflammatory properties via
      inhibiting GSK3beta activity in LPS-induced RAW264.7 macrophages.
AB  - Benzoxazole and its derivatives have been widely studied in recent years due to
      their various biological properties. A previous study has demonstrated that K313
      (1H-indole-2,3-dione 3-(1,3-benzoxazol-2-ylhydrazone)), a novel benzoxazole
      derivative, inhibits T cell proliferation to yield immunosuppressive effects.
      However, there are no related reports about its anti-inflammatory effects. In the
      present study, we investigated the anti-inflammatory properties and the
      underlying molecular mechanism of K313 in lipopolysaccharide (LPS)-induced
      RAW264.7 macrophages. K313 dose-dependently (5, 10, and 20 MUM) inhibited LPS
      stimulated nitric oxide (NO), interleukin (IL)-6, tumor necrosis factor (TNF)
      alpha, and 3-nitrotyrosine (3-NT) production and significantly decreased the gene
      transcription levels of inducible nitric oxide (iNOS), IL-6, and TNF-alpha. In
      addition, the results showed that the inflammatory cytokines suppressed by K313
      were not regulated by p65 NF-kappaB, ERK1/2, AKT, or p38 MAPK. Instead, K313
      increased phosphorylation of glycogen synthase kinase-3 beta (GSK-3beta) (Ser9)
      resulting in GSK-3beta deactivation. Moreover, in LPS-stimulated RAW264.7
      macrophages, K313 and lithium chloride (LiCl) had a synergistic effect on the
      anti-inflammatory response. These results indicated that K313 exhibited anti
      inflammatory properties and revealed the potential mechanism. K313 can increase
      GSK-3beta (Ser9) phosphorylation to decrease GSK-3beta activation in LPS-induced
      RAW264.7 macrophages.

PMID- 29345352
TI  - Achyranthes bidentata polysaccharide suppresses osteoclastogenesis and bone
      resorption via inhibiting RANKL signaling.
AB  - Osteoclasts are highly differentiated multinucleated giant cells that play
      fundamental roles in bone resorption and in the pathogenesis of osteolytic
      conditions, such as osteoporosis and cancer-induced bone loss. Achyranthes
      bidentata polysaccharide (ABP) is a hydrophilic compound with anti-oxidation and
      anti-aging characteristics. The impact of ABP on RANKL-induced osteoclast
      formation and bone resorption has not been assessed, hence, in this study we
      investigated the effect of ABP on osteoclast formation and resorption in murine
      bone marrow derived osteoclasts. We found that ABP was able to suppress RANKL
      induced osteoclast differentiation and bone resorption activity at concentrations
      above 6.5 uM, while demonstrating no cytotoxicity at concentrations up to 10 uM.
      The actions of ABP were mediated through inhibition of RANKL-induced c-Fos and
      NFATc1 gene and protein expression. Furthermore, we found that ABP suppressed
      NFATc1 transcriptional activity, and the phosphorylation of MAPK pathways induced
      by RANKL. Collectively, ABP attenuates RANKL-mediated osteoclast activity and
      signaling, and might serve as a potential therapeutic candidate for preventing
      bone loss related diseases.

PMID- 29345353
TI  - HipOP mesenchymal population has high potential for repairing injured peripheral
      nerves.
AB  - Bone marrow stromal cells (BMSCs) are reportedly a heterogeneous population of
      mesenchymal stem cells (MSCs). Recently, we developed a simple strategy for the
      enrichment of MSCs with the capacity to differentiate into osteoblasts,
      chondrocytes, and adipocytes. On transplantation, the progenitor-enriched
      fractions can regenerate the bone with multiple lineages of donor origin and are
      thus called "highly purified osteoprogenitors" (HipOPs). Although our previous
      studies have demonstrated that HipOPs are enriched with MSCs and exhibit a higher
      potential to differentiate into osteoblasts, adipocytes, and chondrocytes than
      BMSCs, their potential to differentiate into neural cells has not been clarified.
      In this study, we evaluated the efficacy of HipOPs as a resource of neural stem
      cells. The neurosphere assay showed that neurospheres formed by HipOPs exhibited
      self-renewal ability and their size was generally larger than that of
      neurospheres formed by BMSCs. A limiting dilution assay was used to evaluate the
      frequency of neural progenitors in BMSCs and HipOPs. The results demonstrated
      that the frequency of neural progenitors in HipOPs was 120-fold higher than that
      in BMSCs. Furthermore, to investigate the in vivo regenerative potential of the
      peripheral nerve, we modified a murine peripheral nerve injury experimental model
      and demonstrated that HipOPs exhibit a higher efficacy in repairing injured
      peripheral nerves. These findings suggest that HipOPs are a useful cell resource
      for regenerative therapies such as that in case of peripheral nerve injury.

PMID- 29345354
TI  - Lack of functional selectin-ligand interactions enhances innate immune resistance
      to systemic Listeria monocytogenes infection.
AB  - Selectin-ligand interactions are important for leukocyte homing and
      functionality. The roles of selectin-ligand interactions in modulating immunity
      to intracellular infections are not completely understood. Mice lacking the
      expression of fucosyltransferase-IV and -VII (Fucosyltransferase-IV and -VII
      double knockout, FtDKO) exhibit deficient functionality of selectin-ligand
      interactions. We addressed the kinetics of infection and immunity to Listeria
      monocytogenes (LM), an intracellular pathogen, in FtDKO mice. These mice
      exhibited enhanced ability to clear infection and increased survival to a lethal
      dose of LM infection relative to wild-type (WT) C57BL/6J controls. This was
      associated with increased levels of neutrophils, monocytes, and dendritic cells
      (DCs) in the blood and/or infected organs. Adoptive transfer of bone marrow (BM)
      cells from FtDKO mice to WT mice resulted in enhanced neutrophil numbers and
      improved clearance of LM bacteria in recipients. In vivo depletion of myeloid
      innate immune cells, particularly neutrophils, monocytes, macrophages, and DCs,
      using anti-Ly-6G (RB6-8C5) monoclonal antibody, reduced the ability of FtDKO mice
      to curtail LM infection. Nevertheless, depletion using anti-Ly-6G (1A8) known to
      exclusively deplete neutrophils did not abrogate increased resistance of FtDKO
      mice to LM infection, suggesting a role for other myeloid innate immune cells in
      this model. Examination of BM hematopoietic progenitors through flow cytometry
      and cell culture colony-forming unit assay showed increased frequencies of
      granulocyte-macrophage progenitors in FtDKO relative to WT mice, Overall, our
      results indicate that functional selectin ligand deficiency enhances innate
      immune-mediated resistance to systemic LM infection despite defective leukocyte
      migration and lymphocyte homing.

PMID- 29345355
TI  - Effects of antioxidants on apoptosis induced by dasatinib and nilotinib in K562
      cells.
AB  - In clinical practice for the treatment of chronic myeloid leukemia, second
      generation of tyrosine kinase inhibitors such as Nilotinib (NIL) specific and
      potent inhibitor of the BCR/ABL kinase and Dasatinib (DAS) a inhibitor of BCR/ABL
      and Src family kinase were developed to clinically overcome imatinib resistance.
      In this study, we wanted to test the ability of some antioxidants such
      Resveratrol (RES) or a new recombinant mitochondrial manganese containing
      superoxide dismutase (rMnSOD) or delta-tocotrienol (delta-TOCO) to interact with
      DAS and NIL on viability, reactive oxygen species (ROS) production, lipid
      peroxidation, and apoptosis. To test the possible mechanisms of action of such
      antioxidants, we utilized N-acetyl-L-cysteine (NAC) a specific inhibitor ROS
      production or PP1 a specific Src tyrosine kinase inhibitor or BAPTA a specific
      chelator of intracellular calcium. Our data demonstrated: 1) RES, rMnSOD, delta
      TOCO, and NAC, at dose used, significantly reduced the intracellular levels of
      MDA induced by DAS or NIL; 2) RES, rMnSOD, and delta-TOCO increased the
      intracellular ROS levels; 3) The increase ROS levels is related to higher levels
      of oligonucleosomesi induced by DAS and NIL and that NAC significantly reduced
      this activity. Interestingly, our data showed that apoptotic activity of DAS and
      NIL have significantly increased the production of oligonucleosomes by triggering
      excessive ROS generation as well as functionality of SERCA receptors.

PMID- 29345356
TI  - Ethical and Practical Considerations in the Use of a Predictive Model to Trigger
      Suicide Prevention Interventions in Healthcare Settings.
AB  - Predictive models that utilize data from electronic healthcare records (EHR) have
      been developed, investigated, and appear to provide an important resource for
      suicide prevention in medical settings. Actuarial approaches to predicting
      suicide may be particularly important given the relative inability of clinicians
      to accurately predict suicide. Although research regarding predictive models that
      utilize EHR is certainly promising, ethical considerations for the use of these
      models to trigger suicide prevention interventions warrant careful consideration.
      The current manuscript discusses ethical considerations regarding the use of
      predictive models in suicide prevention clinical care. The unique characteristics
      of suicide are explored in terms of how they inform ethical and practical
      approaches. Additionally, biomedical ethical principles and utilitarian, Kantian,
      and personal rights ethical models are applied to the topic. Recommendations for
      navigating the ethical issues are provided as an initial framework for others who
      are considering the implementation of a predictive model to trigger suicide
      prevention initiatives.

PMID- 29345358
TI  - Editorial: Two MDSC faces in obesity: Correcting metabolic dysfunctions but
      promoting tumor development.

PMID- 29345357
TI  - The prognostic value of PI3K mutational status in breast cancer: A meta-analysis.
AB  - Breast cancer (BC) is the second most common cause of cancer-related deaths in
      women worldwide. The availability of reliable biomarkers of response/resistance
      to cancer treatments would benefit patients and clinicians allowing for a better
      selection of BC patients most likely to respond to a specific treatment.
      Phosphatidylinositol 3-kinase (PI3K) enzymes are involved in numerous cellular-
      functions and processes. The gene encoding for PI3K catalytic subunit p110alpha
      is mutated in 20-40% of BC. We performed a meta-analysis of the current
      literature on randomized clinical trials, investigating the role of PIK3CA
      mutational status as prognostic factor, and predictor of response to anti-cancer
      treatments. Overall 1929 cases were included. The pooled analysis confirmed that
      the presence of a PIK3CA mutation represents an independent negative prognostic
      factor (HR = 1.67, 95%CI: 1.15-2.43; P = 0.007) in BC, as previously reported. As
      PI3K signaling is also a result of other pathways' hyperactivation, further
      investigation of potential biomarkers able to predict likelihood of response to
      anti-PI3K/mTOR, anti-HER2, and other TKRs is warranted in future randomized
      clinical trials.

PMID- 29345359
TI  - PDZ proteins are expressed and regulated in antigen-presenting cells and are
      targets of influenza A virus.
AB  - In this work, we identified the expression, regulation, and viral targeting of
      Scribble and Dlg1 in antigen-presenting cells. Scribble and Dlg1 belong to the
      family of PDZ (postsynaptic density (PSD95), disc large (Dlg), and zonula
      occludens (ZO-1)) proteins involved in cell polarity. The relevance of PDZ
      proteins in cellular functions is reinforced by the fact that many viruses
      interfere with host PDZ-dependent interactions affecting cellular mechanisms thus
      favoring viral replication. The functions of Scribble and Dlg have been widely
      studied in polarized cells such as epithelial and neuron cells. However, within
      the cells of the immune system, their functions have been described only in T and
      B lymphocytes. Here we demonstrated that Scribble and Dlg1 are differentially
      expressed during antigen-presenting cell differentiation and dendritic cell
      maturation. While both Scribble and Dlg1 seem to participate in distinct
      dendritic cell functions, both are targeted by the viral protein NS1 of influenza
      A in a PDZ-dependent manner in dendritic cells. Our findings suggest that these
      proteins might be involved in the mechanisms of innate immunity and/or antigen
      processing and presentation that can be hijacked by viral pathogens.

PMID- 29345360
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- 29345361
TI  - Immunotherapy for cardiovascular disease.
AB  - Heart failure (HF), the final stage of pathological cardiac hypertrophy, is a
      major cause of hospitalization and mortality. The role of inflammation in the
      pathogenesis of HF has been extensively studied, with great emphasis on
      proinflammatory cytokines. Yet, clinical trials targeting these cytokines failed
      to become a credible therapeutic strategy for HF. More recent studies are
      increasingly highlighting an active role for T cells in the progression of HF
      pathology. As a result, a number of novel immunotherapy strategies are emerging
      for the treatment of HF and other cardiovascular diseases, via the targeting of
      adaptive immunity. Here we provide an overview of the background, details, and
      expected outcomes of these attempts.

PMID- 29345362
TI  - Innate lymphoid cells in antitumor immunity.
AB  - Innate lymphoid cells (ILCs) are the most recently characterized subset of innate
      lymphocytes. Based on their specific transcriptional regulation, cytokine
      secretion pattern and effector functions ILCs mirror the different CD4 T helper
      cell subsets, with the unique attributes of acting locally in early phases of
      immune responses, in an antigen-independent manner. In this review, we discuss
      how ILCs have been implicated in tumorigenesis. Their presence might favor or
      inhibit tumor growth, depending on the cytokines released and the specific tumor
      microenvironment. As our understanding of ILCs' contribution to antitumor
      responses advances, clinical options to target ILCs in antitumor therapies are
      also emerging.

PMID- 29345363
TI  - Effects of IL-10 and Th 2 cytokines on human Mphi phenotype and response to CSF1R
      inhibitor.
AB  - Tumor-associated Mphis display a plastic phenotype that is regulated by the local
      tumor milieu. Gene expression analysis and functional characterization of Mphis
      exposed in vitro to individual cytokines aids to delineate the cross-talk between
      defined cytokines shaping the complex Mphi phenotype. Human monocyte-derived
      Mphis can be differentiated in vitro with the T helper cell type 2 response
      cytokines IL-4 and IL-13 or the immunosuppressive IL-10. Notably, only the latter
      subset undergoes apoptosis when treated with the CSF 1 receptor (CSF1R) blocking
      antibody emactuzumab. However, under physiologic conditions, the Mphi phenotype
      is regulated by cytokine combination. Hence, in this study, we characterized the
      plasticity of IL-4 or IL-13-differentiated Mphis upon exposure to the
      immunosuppressive IL-10. Although IL-4-differentiated Mphis sustained their
      molecular phenotype in the presence of IL-10, IL-13-differentiated Mphis were
      skewed towards the IL-10 phenotype. Gene expression profiling revealed unique IL
      4+IL-10 and IL-13+IL-10 Mphi signatures associated with up-regulation of
      canonical NF-kappaB or Wnt/beta-catenin signaling pathways, respectively.
      Although IL-10 was able to alter the surface marker and gene expression profile
      of IL-13-differentiated Mphis, addition of IL-10 did not restore emactuzumab
      susceptibility. Combining NF-kappaB and Wnt/beta-catenin signaling inhibitors
      with emactuzumab had no effect on viability. On average 3-5% of cancer patients
      overexpressed IL-4, IL-13, or IL-10 mRNA in silico. Although a small patient
      subset overexpressed IL-10+IL-13, IL-4+IL-10 lacked co-expression. In vitro
      characterization of CSF1R inhibitor-refractory Mphi phenotypes can support novel
      pharmacological approaches to specifically target these cells.

PMID- 29345364
TI  - The N-terminal peptide moiety of the Mycobacterium tuberculosis 19 kDa
      lipoprotein harbors RP105-agonistic properties.
AB  - Radioprotective 105 kDa (RP105, CD180) is a member of the Toll-like receptor
      (TLR) family that interacts with TLR2 and facilitates recognition of mature
      lipoproteins expressed by Mycobacterium tuberculosis and Mycobacterium bovis BCG.
      In this study, we used synthetic lipopeptide analogs of the M. tuberculosis 19
      kDa lipoprotein to define structural characteristics that promote RP105-mediated
      host cell responses. A tripalmitoylated lipopeptide composed of the first 16 N
      terminal amino acids of the M. tuberculosis 19 kDa lipoprotein induced RP105
      dependent TNF and IL-6 production by macrophages. Di- and tripalmitoylated
      variants of this lipopeptide elicited an equivalent RP105-dependent response,
      indicating that while the lipid moiety is required for macrophage activation, it
      is not a determinant of RP105 dependency. Instead, substitution of two polar
      threonine residues at positions 7 and 8 with nonpolar alanine residues resulted
      in reduced RP105 dependency. These results strongly suggest that the amino acid
      composition of the M. tuberculosis 19 kDa lipoprotein, and likely other
      mycobacterial lipoproteins, is a key determinant of RP105 agonism.

PMID- 29345365
TI  - Deletion of BCG Hip1 protease enhances dendritic cell and CD4 T cell responses.
AB  - Dendritic cells (DCs) play a key role in the generation of CD4 T cell responses
      to pathogens. Mycobacterium tuberculosis (Mtb) harbors immune evasion mechanisms
      that impair DC responses and prevent optimal CD4 T cell immunity. The vaccine
      strain Mycobacterium bovis Bacille Calmette-Guerin (BCG) shares many of the
      immune evasion proteins utilized by Mtb, but the role of these proteins in DC and
      T cell responses elicited by BCG is poorly understood. We previously reported
      that the Mtb serine protease, Hip1, promotes sub-optimal DC responses during
      infection. Here, we tested the hypothesis that BCG Hip1 modulates DC functions
      and prevents optimal antigen-specific CD4 T cell responses that limit the
      immunogenicity of BCG. We generated a strain of BCG lacking hip1 (BCGDeltahip1)
      and show that it has superior capacity to induce DC maturation and cytokine
      production compared with the parental BCG. Furthermore, BCGDeltahip1-infected DCs
      were more effective at driving the production of IFN-gamma and IL-17 from antigen
      specific CD4 T cells in vitro. Mucosal transfer of BCGDeltahip1-infected DCs into
      mouse lungs induced robust CD4 T cell activation in vivo and generated antigen
      specific polyfunctional CD4 T cell responses in the lungs. Importantly,
      BCGDeltahip1-infected DCs enhanced control of pulmonary bacterial burden
      following Mtb aerosol challenge compared with the transfer of BCG-infected DCs.
      These results reveal that BCG employs Hip1 to impair DC activation, leading to
      attenuated lung CD4 T cell responses with limited capacity to control Mtb burden
      after challenge.

PMID- 29345366
TI  - Interactions between the microbiota and innate and innate-like lymphocytes.
AB  - The microbiota, which consists of commensal bacteria, fungi, and viruses, limits
      the colonization of pathogens at barrier tissues and promotes immune homeostasis.
      The latter is accomplished through the induction and regulation of both innate
      and adaptive immune responses. Innate lymphocytes, which include the type-1
      innate lymphoid cell (ILC1), NK cell, type-2 innate lymphoid cell (ILC2), type-3
      innate lymphoid cell (ILC3), and lymphoid tissue inducer (LTi) cell populations,
      and innate-like lymphocytes, such as NKT cells, mucosal-associated invariant T
      (MAIT) cells, and gammadelta T cells, are uniquely capable of responding to the
      microbiota due to their tissue localization and rapid primary responses. In turn,
      through their effector functions, these lymphocyte populations modulate the
      composition of the microbiota and maintain the segregation of commensals. This
      review will focus on how innate and innate-like lymphocytes mediate the crosstalk
      with the microbiome.

PMID- 29345367
TI  - CD300 family receptors regulate eosinophil survival, chemotaxis, and effector
      functions.
AB  - The CD300 family of receptors is an evolutionary conserved receptor family that
      belongs to the Ig superfamily and is expressed predominantly by the myeloid
      lineage. Over the past couple of years, accumulating data have shown that
      eosinophils express various Ig superfamily receptors that regulate key
      checkpoints in their biology including their maturation, transition from the bone
      marrow to the peripheral blood, migration, adhesion, survival, and effector
      functions in response to numerous activating signals such as IL-4, IL-33, and
      bacteria. In this review, we will present the emerging roles of CD300 family
      receptors and specifically CD300a and CD300f in the regulation of these
      eosinophil activities. The structure and expression pattern of these molecules
      will be discussed and their involvement in suppressing or co-activating
      eosinophil functions in health and disease will be illustrated.

PMID- 29345368
TI  - Therapeutic effect of Lipoxin A4  in malaria-induced acute lung injury.
AB  - Acute lung injury (ALI) models are characterized by neutrophil accumulation,
      tissue damage, alteration of the alveolar capillary membrane, and physiological
      dysfunction. Lipoxin A4  (LXA4 ) is an anti-inflammatory eicosanoid that was
      demonstrated to attenuate lipopolysaccharide-induced ALI. Experimental models of
      severe malaria can be associated with lung injury. However, to date, a putative
      effect of LXA4  on malaria (M)-induced ALI has not been addressed. In this study,
      we evaluated whether LXA4 exerts an effect on M-ALI. Male C57BL/6 mice were
      randomly assigned to the following five groups: noninfected; saline-treated
      Plasmodium berghei-infected; LXA4 -pretreated P. berghei-infected (LXA4 
      administered 1 h before infection and daily, from days 0 to 5 postinfection),
      LXA4 - and LXA4 receptor antagonist BOC-2-pretreated P. berghei-infected; and
      LXA4 -posttreated P. berghei-infected (LXA4  administered from days 3 to 5
      postinfection). By day 6, pretreatment or posttreatment with LXA4  ameliorate
      lung mechanic dysfunction reduced alveolar collapse, thickening and interstitial
      edema; impaired neutrophil accumulation in the pulmonary tissue and blood; and
      reduced the systemic production of CXCL1. Additionally, in vitro treatment with
      LXA4 prevented neutrophils from migrating toward plasma collected from P. berghei
      infected mice. LXA4  also impaired neutrophil cytoskeleton remodeling by
      inhibiting F-actin polarization. Ex vivo analysis showed that neutrophils from
      pretreated and posttreated mice were unable to migrate. In conclusion, we
      demonstrated that LXA4  exerted therapeutic effects in malaria-induced ALI by
      inhibiting lung dysfunction, tissue injury, and neutrophil accumulation in lung
      as well as in peripheral blood. Furthermore, LXA4 impaired the migratory ability
      of P. berghei-infected mice neutrophils.

PMID- 29345369
TI  - Memory B cell heterogeneity: Remembrance of things past.
AB  - B cells that persist for long periods of time after antigen encounter exist as
      either antibody-producing plasma cells (long-lived plasma cells, LLPCs) that
      reside primarily in the bone marrow or rapidly responsive memory B cells (MBCs)
      that reside in the spleen and circulation. Although LLPCs are thought to be non
      responsive to a secondary infection, MBCs respond to subsequent infection through
      the production of antibody-secreting cells, formation of new germinal centers
      (GCs), and repopulation of the memory pool. Dogma suggests that MBCs express
      class-switched, somatically hypermutated BCRs after undergoing a GC reaction. Yet
      this narrow view of MBCs has been challenged over the years and it is now well
      recognized that diverse MBC subsets exist in both rodents and humans. Here, we
      review current thoughts on the phenotypic and functional characteristics of MBCs,
      focusing on a population of somatically hypermutated, high affinity IgM+ MBCs
      that are rapidly responsive to a secondary malaria infection.

PMID- 29345371
TI  - Therapeutic manipulation of host cell death pathways to facilitate clearance of
      persistent viral infections.
AB  - Most persistent viral infections can be controlled, but not cured, by current
      therapies. Abrogated antiviral immunity and stable latently infected cells
      represent major barriers to cure. This necessitates life-long suppressive
      antiviral therapy. Achieving a cure for HIV, hepatitis B virus, Epstein Barr
      virus, and others, requires novel approaches to facilitate the clearance of
      infected cells from the host. One such approach is to target host cell death
      pathways, rather than the virus itself. Here, we summarize recent findings from
      studies that have utilized therapeutics to manipulate host cell death pathways as
      a means to treat and cure persistent viral infections.

PMID- 29345370
TI  - Inhibition of soluble epoxide hydrolase attenuates eosinophil recruitment and
      food allergen-induced gastrointestinal inflammation.
AB  - Prevalence of food allergies in the United States is on the rise. Eosinophils are
      recruited to the intestinal mucosa in substantial numbers in food allergen-driven
      gastrointestinal (GI) inflammation. Soluble epoxide hydrolase (sEH) is known to
      play a pro-inflammatory role during inflammation by metabolizing anti
      inflammatory epoxyeicosatrienoic acids (EETs) to pro-inflammatory diols. We
      investigated the role of sEH in a murine model of food allergy and evaluated the
      potential therapeutic effect of a highly selective sEH inhibitor (trans-4-{4-[3
      (4-trifluoromethoxyphenyl)-ureido]-cyclohexyloxy}-benzoic acid [t-TUCB]). Oral
      exposure of mice on a soy-free diet to soy protein isolate (SPI) induced
      expression of intestinal sEH, increased circulating total and antigen-specific
      IgE levels, and caused significant weight loss. Administration of t-TUCB to SPI
      challenged mice inhibited IgE levels and prevented SPI-induced weight loss.
      Additionally, SPI-induced GI inflammation characterized by increased recruitment
      of eosinophils and mast cells, elevated eotaxin 1 levels, mucus hypersecretion,
      and decreased epithelial junction protein expression. In t-TUCB-treated mice,
      eosinophilia, mast cell recruitment, and mucus secretion were significantly lower
      than in untreated mice and SPI-induced loss of junction protein expression was
      prevented to variable levels. sEH expression in eosinophils was induced by
      inflammatory mediators TNF-alpha and eotaxin-1. Treatment of eosinophils with t
      TUCB significantly inhibited eosinophil migration, an effect that was mirrored by
      treatment with 11,12-EET, by inhibiting intracellular signaling events such as
      ERK (1/2) activation and eotaxin-1-induced calcium flux. These studies suggest
      that sEH induced by soy proteins promotes allergic responses and GI inflammation
      including eosinophilia and that inhibition of sEH can attenuate these responses.

PMID- 29345372
TI  - Truncation of neurokinin-1 receptor-Negative regulation of substance P signaling.
AB  - Substance P (SP) is a tachykinin peptide, which triggers intracellular signaling
      in the nervous and immune systems, as well as, other local and systemic events.
      The interaction between SP and its receptor, neurokinin-1 receptor (NK1R),
      results in major downstream cellular actions, which include changes in calcium
      fluxes, ERK, and p21-activated kinase phosphorylation and NFkappaB activation.
      Two naturally occurring variants of the NK1R, the full-length, 407 aa receptor
      (NK1R-F) and the truncated, 311 aa isoform (NK1R-T), mediate the actions of SP.
      Receptor truncation partially disrupts signaling motifs of the carboxyl tail, a
      critical site for mediating NK1R signaling, resulting in a "less-efficient"
      receptor. Although NK1R-F is the predominant isoform in the central and
      peripheral nervous systems, NK1R-T is expressed in several tissues and cells,
      which include monocytes, NK cells, and T-cells. The SP binding domain is not
      affected by truncation and this site is identical in both NK1R receptor isoforms.
      However, while cells expressing NK1R-F respond to nanomolar concentrations of SP,
      monocyte and macrophage activation, mediated through NK1R-T, requires micromolar
      concentrations of SP in order to elicit signaling responses. Elevated plasma
      levels of SP are associated with increased inflammatory responses and NK1R
      antagonists reduce inflammation and cytokine production in vivo. This mini review
      presents and discusses the novel hypothesis that the expression of NK1R-T on
      immune system cells prevents immune activation in a milieu, which usually
      contains low concentrations of SP and, thus, maintains immune homeostasis. In
      contrast, in the activated neuronal microenvironment, when SP levels reach the
      threshold at tissue sites, SP promotes immune activation and modulates
      monocyte/macrophage polarization.

PMID- 29345373
TI  - Macrophage instructs neutrophil death.

PMID- 29345374
TI  - SHIP negatively regulates type II immune responses in mast cells and macrophages.
AB  - SHIP is a hematopoietic-specific lipid phosphatase that dephosphorylates PI3K
      generated PI(3,4,5)-trisphosphate. SHIP removes this second messenger from the
      cell membrane blunting PI3K activity in immune cells. Thus, SHIP negatively
      regulates mast cell activation downstream of multiple receptors. SHIP has been
      referred to as the "gatekeeper" of mast cell degranulation as loss of SHIP
      dramatically increases degranulation or permits degranulation in response to
      normally inert stimuli. SHIP also negatively regulates Mphi activation, including
      both pro-inflammatory cytokine production downstream of pattern recognition
      receptors, and alternative Mphi activation by the type II cytokines, IL-4, and IL
      13. In the SHIP-deficient (SHIP-/- ) mouse, increased mast cell and Mphi
      activation leads to spontaneous inflammatory pathology at mucosal sites, which is
      characterized by high levels of type II inflammatory cytokines. SHIP-/- mast
      cells and Mphis have both been implicated in driving inflammation in the SHIP-/-
      mouse lung. SHIP-/- Mphis drive Crohn's disease-like intestinal inflammation and
      fibrosis, which is dependent on heightened responses to innate immune stimuli
      generating IL-1, and IL-4 inducing abundant arginase I. Both lung and gut
      pathology translate to human disease as low SHIP levels and activity have been
      associated with allergy and with Crohn's disease in people. In this review, we
      summarize seminal literature and recent advances that provide insight into SHIP's
      role in mast cells and Mphis, the contribution of these cell types to pathology
      in the SHIP-/- mouse, and describe how these findings translate to human disease
      and potential therapies.

PMID- 29345375
TI  - Understanding the regulation of APOBEC3 expression: Current evidence and much to
      learn.
AB  - The apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3 (APOBEC3)
      family of cytosine deaminases plays crucial roles in innate immunity through the
      ability of restricting viral replication by deamination and mutation of viral
      genomes. The antiviral function of these proteins was first discovered when
      research in the field of HIV infection revealed that one member of the family,
      namely APOBEC3G, restricts HIV infection in T lymphocytes and that the viral
      infectivity factor protein drives the proteosomal degradation of this enzyme,
      thus overriding its antiviral function. Recent advances in cancer genomics,
      together with biochemical characterization of the APOBEC3 enzymes, have now
      implicated some family members in somatic mutagenesis during carcinogenesis.
      While several studies investigated the downstream consequences of APOBEC3
      expression and activity, either in the context of viral infection or
      tumorigenesis, little is known on the upstream mechanisms regulating APOBEC3
      expression. Such knowledge would be of huge importance in developing innovative
      approaches to strengthen antiviral innate immunity on one side and to prevent
      cancer development on the other. This mini review summarizes research advances on
      the molecular mechanisms regulating the expression of APOBEC3 family members in
      selected immune cell populations and cancer cells.

PMID- 29345377
TI  - Flexoelectricity in Bones.
AB  - Bones generate electricity under pressure, and this electromechanical behavior is
      thought to be essential for bone's self-repair and remodeling properties. The
      origin of this response is attributed to the piezoelectricity of collagen, which
      is the main structural protein of bones. In theory, however, any material can
      also generate voltages in response to strain gradients, thanks to the property
      known as flexoelectricity. In this work, the flexoelectricity of bone and pure
      bone mineral (hydroxyapatite) are measured and found to be of the same order of
      magnitude; the quantitative similarity suggests that hydroxyapatite
      flexoelectricity is the main source of bending-induced polarization in cortical
      bone. In addition, the measured flexoelectric coefficients are used to calculate
      the (flexo)electric fields generated by cracks in bone mineral. The results
      indicate that crack-generated flexoelectricity is theoretically large enough to
      induce osteocyte apoptosis and thus initiate the crack-healing process,
      suggesting a central role of flexoelectricity in bone repair and remodeling.

PMID- 29345376
TI  - Role of negative regulation of immune signaling pathways in neutrophil function.
AB  - Polymorphonuclear neutrophils (PMNs) play a critical role in host defense against
      infection and in the resolution of inflammation. However, immune responses
      mediated by PMN must be tightly regulated to facilitate elimination of invading
      pathogens without inducing detrimental inflammation and host tissue damage.
      Specific engagement of cell surface immunoreceptors by a diverse range of
      extracellular signals regulates PMN effector functions through differential
      activation of intracellular signaling cascades. Although mechanisms of PMN
      activation mediated via cell signaling pathways have been well described, less is
      known about negative regulation of PMN function by immune signaling cascades.
      Here, we provide an overview of immunoreceptor-mediated negative regulation of
      key PMN effector functions including maturation, migration, phagocytosis,
      reactive oxygen species release, degranulation, apoptosis, and NET formation.
      Increased understanding of mechanisms of suppression of PMN effector functions
      may point to possible future therapeutic targets for the amelioration of PMN
      mediated autoimmune and inflammatory diseases.

PMID- 29345378
TI  - Self-Calibrating Mechanochromic Fluorescent Polymers Based on Encapsulated
      Excimer-Forming Dyes.
AB  - While mechanochemical transduction principles are omnipresent in nature,
      mimicking these in artificial materials is challenging. The ability to reliably
      detect the exposure of man-made objects to mechanical forces is, however, of
      great interest for many applications, including structural health monitoring and
      tamper-proof packaging. A useful concept to achieve mechanochromic responses in
      polymers is the integration of microcapsules, which rupture upon deformation and
      release a payload causing a visually detectable response. Herein, it is reported
      that this approach can be used to create mechanochromic fluorescent materials
      that show a direct and ratiometric response to mechanical deformation. This can
      be achieved by filling poly(urea-formaldehyde) microcapsules with a solution of a
      photoluminescent aggregachromic cyano-substituted oligo(p-phenylene vinylene) and
      embedding these particles in poly(dimethylsiloxane). The application of
      mechanical force by way of impact, incision, or tensile deformation opens the
      microcapsules and releases the fluorophore in the damaged area. Due to excimer
      formation, the subsequent aggregation of the dye furnishes a detectable
      fluorescence color change. With the emission from unopened microcapsules as built
      in reference, the approach affords materials that are self-calibrating. This new
      concept appears to be readily applicable to a range of polymer matrices and
      allows for the straightforward assessment of their structural integrity.

PMID- 29345379
TI  - Sphingolipids role in the regulation of inflammatory response: From leukocyte
      biology to bacterial infection.
AB  - Sphingolipids (SLs) are amphiphilic molecules mainly associated with the external
      leaflet of eukaryotic plasma membrane, and are structural membrane components
      with key signaling properties. Since the beginning of the last century, a large
      number of papers described the involvement of these molecules in several aspects
      of cell physiology and pathology. Several lines of evidence support the critical
      role of SLs in inflammatory diseases, by acting as anti- or pro-inflammatory
      mediators. They are involved in control of leukocyte activation and migration,
      and are recognized as essential players in host response to pathogenic infection.
      We propose here a critical overview of current knowledge on involvement of
      different classes of SLs in inflammation, focusing on the role of simple and
      complex SLs in pathogen-mediated inflammatory response.

PMID- 29345380
TI  - CIRP increases ICAM-1+ phenotype of neutrophils exhibiting elevated iNOS and NETs
      in sepsis.
AB  - Sepsis represents uncontrolled inflammation due to an infection. Cold-inducible
      RNA-binding protein (CIRP) is a stress-induced damage-associated molecular
      pattern (DAMP). A subset of neutrophils expressing ICAM-1+ neutrophils was
      previously shown to produce high levels of reactive oxygen species. The role of
      CIRP for the development and function of ICAM-1+ neutrophils during sepsis is
      unknown. We hypothesize that CIRP induces ICAM-1 expression in neutrophils
      causing injury to the lungs during sepsis. Using a mouse model of cecal ligation
      and puncture (CLP)-induced sepsis, we found increased expression of CIRP and
      higher frequencies and numbers of ICAM-1+ neutrophils in the lungs. Conversely,
      the CIRP-/- mice showed significant inhibition in the frequencies and numbers of
      ICAM-1+ neutrophils in the lungs compared to wild-type (WT) mice in sepsis. In
      vitro treatment of bone marrow-derived neutrophils (BMDN) with recombinant murine
      CIRP (rmCIRP) significantly increased ICAM-1+ phenotype in a time- and dose
      dependent manner. The effect of rmCIRP on increasing frequencies of ICAM-1+
      neutrophils was significantly attenuated in BMDN treated with anti-TLR4 Ab or NF
      kappaB inhibitor compared, respectively, with BMDN treated with isotype IgG or
      DMSO. The frequencies of iNOS producing and neutrophil extracellular traps (NETs)
      forming phenotypes in rmCIRP-treated ICAM-1+ BMDN were significantly higher than
      those in ICAM-1- BMDN. Following sepsis the ICAM-1+ neutrophils in the lungs
      showed significantly higher levels of iNOS and NETs compared to ICAM-1-
      neutrophils. We further revealed that ICAM-1 and NETs were co-localized in the
      neutrophils treated with rmCIRP. CIRP-/- mice showed significant improvement in
      their survival outcome (78% survival) over that of WT mice (48% survival) in
      sepsis. Thus, CIRP could be a novel therapeutic target for regulating iNOS
      producing and NETs forming ICAM-1+ neutrophils in the lungs during sepsis.

PMID- 29345381
TI  - Durable lesion formation while avoiding esophageal injury during ablation of
      atrial fibrillation: Lessons learned from late gadolinium MR imaging.
AB  - INTRODUCTION: Adequate catheter/atrial tissue contact is critical for lesion
      formation during radiofrequency (RF) ablation of atrial fibrillation (AF). Late
      gadolinium enhancement magnetic resonance imaging (LGE-MRI) is a unique tool for
      the evaluation of lesion formation and detection of acute esophageal injury.
      METHODS: LGE-MRIs were obtained prior, within 24 hours of, and at 115 +/- 62 days
      after first AF ablation in 36 patients. The Visitag module of CARTO3 was used to
      collect contact force (CF) and duration from a CF sensing ablation catheter for
      each registered ablation point. The minimum CF resulting in permanent lesions was
      determined. Esophageal enhancement detected by acute LGE-MRI was classified as
      mild, moderate, and severe. The CF resulting in esophageal enhancement was
      determined. RESULTS: A total of 4,642 registered ablation tags at 50 W power were
      analyzed. The mean RF duration (5.9 +/- 3.7 vs. 5.6 +/- 3.2 seconds, P < 0.05),
      CF (11.5 +/- 5.6 vs. 10.9 +/- 5.4 g, P < 0.001), and force time integral (FTI)
      (67.3 +/- 54.5 vs. 62.2 +/- 52.7 gs, P < 0.01) were significantly higher between
      ablation tags with and without associated LGE-MRI detected scar. The mean CF
      (15.7 +/- 6.1 vs. 12.6 +/- 5.9 g, P < 0.05, n  =  17 patients) in areas of
      esophageal enhancement was greater than areas without. CONCLUSION: Left atrial
      short duration ablation lesions with a CF greater than 12 g are more likely to be
      associated with permanent lesion formation. Ablating on top of the esophagus, CF
      less than 15 g would help minimize esophageal wall injury.

PMID- 29345382
TI  - Overweight and obesity in patients with atrial fibrillation: Sex differences in 1
      year outcomes in the EORP-AF General Pilot Registry.
AB  - BACKGROUND: The impact of overweight and obesity on outcomes in "real world"
      patients with atrial fibrillation (AF) is not fully defined. Second, sex
      differences in AF outcomes may also exist. METHODS AND RESULTS: The aim was to
      investigate outcomes at 1 year follow-up for AF patients enrolled in the EORP-AF
      Registry, according to BMI (kg/m2 ), comparing patients with normal BMI (18.5 to
      < 25 kg/m2 ), overweight (25 to < 30 kg/m2 ) and obesity (>= 30 kg/m2 ), in
      relation to sex differences. Among 2,540 EORP AF patients (38.9% female; median
      age 69) with 1 year follow-up data available, 720 (28.3%) had a normal BMI, 1,084
      (42.7%) were overweight, and 736 (29.0%) were obese. Obese patients were younger
      and with more prevalent diabetes mellitus and hypertension (P < 0. 001). One-year
      outcomes showed that all-cause mortality was significantly different according to
      BMI among female patients (9.3% normal BMI, 5.3% overweight, and 4.3 % obese, P =
      0.023), but not among male patients (P = 0.748). The composite outcome of
      thromboembolic events and death was also significantly different, being lower in
      obese females (P = 0.035). Among male patients, bleeding events were
      significantly more frequent in obese subjects (P = 0.035). On multivariable Cox
      analysis, BMI was not independently associated with all-cause mortality.
      CONCLUSIONS: Among AF patients, overweight and obesity are common and associated
      with better outcomes in females (a finding previously reported as "obesity
      paradox"), while no significant differences in outcomes are detected among male
      patients. Final multivariable model found that increasing BMI was not associated
      with increased risk of all-cause death; conversely, age and comorbidities
      persisted as major determinants.

PMID- 29345383
TI  - Interesting mode of initiation of LBBB tachycardia: What is the mechanism?

PMID- 29345384
TI  - A Single-Molecule Propyne Trap: Highly Efficient Removal of Propyne from
      Propylene with Anion-Pillared Ultramicroporous Materials.
AB  - Propyne/propylene (C3 H4 /C3 H6 ) separation is a critical process for the
      production of polymer-grade C3 H6 . However, optimization of the structure of
      porous materials for the highly efficient removal of C3 H4 from C3 H6 remains
      challenging due to their similar structures and ultralow C3 H4 concentration.
      Here, it is first reported that hybrid ultramicroporous materials with pillared
      inorganic anions (SiF62- = SIFSIX, NbOF52- = NbOFFIVE) can serve as highly
      selective C3 H4 traps for the removal of trace C3 H4 from C3 H6 . Especially, it
      is revealed that the pyrazine-based ultramicroporous material with square grid
      structure for which the pore shape and functional site disposition can be varied
      in 0.1-0.5 A scale to match both the shape and interacting sites of guest
      molecule is an interesting single-molecule trap for C3 H4 molecule. The pyrazine
      based single-molecule trap enables extremely high C3 H4 uptake under ultralow
      concentration (2.65 mmol g-1 at 3000 ppm, one C3 H4 per unit cell) and record
      selectivity over C3 H6 at 298 K (>250). The single-molecule binding mode for C3
      H4 within ultramicroporous material is validated by X-ray diffraction experiments
      and modeling studies. The breakthrough experiments confirm that anion-pillared
      ultramicroporous materials set new benchmarks for the removal of ultralow
      concentration C3 H4 (1000 ppm on SIFSIX-3-Ni, and 10 000 ppm on SIFSIX-2-Cu-i)
      from C3 H6 .

PMID- 29345385
TI  - Crucial role of Mer tyrosine kinase in the maintenance of SIGN-R1+ marginal zone
      macrophages.
AB  - Mer Tyrosine Kinase receptor (Mer) is involved in anti-inflammatory
      efferocytosis. Here we report elevated spontaneous germinal center (Spt-GC)
      responses in Mer-deficient mice (Mer-/- ) that are associated with the loss of
      SIGN-R1+ marginal zone macrophages (MZMs). The dissipation of MZMs in Mer-/- mice
      occurs independently of reduced cellularity or delocalization of marginal zone B
      cells, sinusoidal cells or of CD169+ metallophillic macrophages. We find that MZM
      dissipation in Mer-/- mice contributes to apoptotic cell (AC) accumulation in Spt
      GCs and dysregulation of the GC checkpoint, allowing an expansion of DNA-reactive
      B cells in GCs. We further observe that bone marrow derived macrophages from Mer
      /- mice produce more TNFalpha, and are susceptible to cell death upon exposure to
      ACs compared to WT macrophages. Anti-TNFalpha Ab treatment of Mer-/- mice is,
      however, unable to reverse MZM loss, but results in reduced Spt-GC responses,
      indicating that TNFalpha promotes Spt-GC responses in Mer-/- mice. Contrary to an
      anti-TNFalpha Ab treatment, treatment of Mer-/- mice with a synthetic agonist for
      the transcription factor LXRalpha rescues a significant number of MZMs in vivo.
      Our data suggest that Mer-LXRalpha signaling plays an important role in the
      differentiation and maintenance of MZMs, which in turn regulate Spt-GC responses
      and tolerance.

PMID- 29345386
TI  - Quinoline-Flanked Diketopyrrolopyrrole Copolymers Breaking through Electron
      Mobility over 6 cm2 V-1 s-1 in Flexible Thin Film Devices.
AB  - Herein, the design and synthesis of novel pi-extended quinoline-flanked
      diketopyrrolopyrrole (DPP) [abbreviated as QDPP] motifs and corresponding
      copolymers named PQDPP-T and PQDPP-2FT for high performing n-type organic field
      effect transistors (OFETs) in flexible organic thin film devices are reported.
      Serving as DPP-flankers in backbones, quinoline is found to effectively tune
      copolymer optoelectric properties. Compared with TDPP and pyridine-flanked DPP
      (PyDPP) analogs, widened bandgaps and strengthened electron deficiency are
      achieved. Moreover, both hole and electron mobility are improved two orders of
      magnitude compared to those of PyDPP analogs (PPyDPP-T and PPyDPP-2FT). Notably,
      featuring an all-acceptor-incorporated backbone, PQDPP-2FT exhibits electron
      mobility of 6.04 cm2 V-1 s-1 , among the highest value in OFETs fabricated on
      flexible substrates to date. Moreover, due to the widened bandgap and
      strengthened electron deficiency of PQDPP, n-channel on/off ratio over 105 with
      suppressed hole transport is first realized in the ambipolar DPP-based
      copolymers.

PMID- 29345387
TI  - Fortuitous benefits of living kidney donation: Diagnosis of serious medical
      conditions during the living donor evaluation.
AB  - BACKGROUND: All living kidney donors are counseled about the possible surgical
      and medical risks associated with donation. Only a minority of transplant centers
      discuss the potential benefit of discovering undiagnosed medical conditions in
      the donor during evaluation, as part of their consent process. METHODS: We
      retrospectively investigated all potential living kidney donors evaluated over a
      10-year period at a single center to characterize incidentally diagnosed serious
      medical conditions. RESULTS: Sixty-five of the 762 potential donors (8.5%) were
      not approved for donation because of a newly diagnosed serious medical condition
      discovered during their evaluation. This included six patients diagnosed with
      malignancies, five of which required operative intervention, six patients
      diagnosed with transmittable diseases requiring follow-up and treatment, four
      patients were found to have bilateral renal stones with significant stone burden,
      and two patients diagnosed with IgA nephropathy. Additionally, four patients were
      diagnosed with significant heart disease, and one of those patients subsequently
      required a coronary artery bypass surgery. CONCLUSIONS: The evaluation process
      can diagnose serious medical conditions in a significant minority of donors that
      would have otherwise been unrecognized. The benefit associated with the donor
      evaluation should be considered an important part of the consent process.

PMID- 29345388
TI  - Dentin bond strength and nanoleakage of the adhesive interface after intracoronal
      bleaching.
AB  - This study evaluated dentin bond strength (BS) and nanoleakage of non- and pre
      etched dentin immediately (T0 ,), 7 days (T7 ), and 14 days (T14 ) after
      bleaching. Bovine incisors (150) were selected and half of them submitted to
      intrapulpal dentin etching (e). Non- and pre-etched dentin were subjected to the
      following (n = 15): no bleaching/control (C); 35% carbamide peroxide (CP); 35%
      hydrogen peroxide (35% HP); 25% hydrogen peroxide (25% HP); and sodium perborate
      (SP). Bleaching agents were applied to the pulp chamber four times within a 72-h
      interval. Afterwards, pulp chamber dentin was prepared for the BS test at
      different evaluation times (n = 5): T0 , T7 , and T14 . Composite blocks were
      built on pulp chamber and sectioned in slices. Slices were reduced to an hour
      glass shape with a cross-sectional area of 0.8 mm2 and submitted to microtensile
      BS test. Two additional specimens for each group were prepared for nanoleakage
      evaluation by transmission electron microscopy (TEM). Results were analyzed by
      ANOVA (two-way) and Dunnett's test (p < .05). BS decreased immediately after
      intracoronal bleaching for both sound and pre-etched dentin (p < .05). At T14 ,
      the BS of non-etched bleached dentin increased for all groups, whereas the pre
      etched SPe group presented BS similar to the Ce. Nanoleakage within the hybrid
      layer was perceptible immediately after bleaching, although a decrease in
      nanoleakage was observed for all groups at T14 . Adhesive restorations should be
      performed 7-14 days after bleaching, according to the bleaching agent used.
      Intracoronal bleaching should be performed preferably with sodium perborate if
      previous dentin etching is applied.

PMID- 29345389
TI  - Percutaneous access to the heart: Nontraditional approaches for the
      electrophysiologist.

PMID- 29345390
TI  - Frontline Science: Wnt/beta-catenin pathway promotes early engraftment of fetal
      hematopoietic stem/progenitor cells.
AB  - The switch from fetal to adult hematopoietic stem/progenitor cells (HSPCs) is
      associated with profound changes in several genetic programs. Although HSPC
      ageing corresponds to alterations in Wnt signaling, relatively little is known
      about the relative roles of different Wnt signaling pathways in HSPC ontogeny. We
      hypothesized that proliferating fetal HSPCs would be more dependent on canonical
      beta-catenin-dependent Wnt signaling when compared to quiescent adult bone marrow
      HSPCs. We have compared here Wnt signaling activities in murine fetal and adult
      HSPCs and demonstrate a shift from Wnt/beta-catenin-dependent signaling in fetal
      liver HSPCs to more predominantly noncanonical Wnt/polarity signaling in adult
      HSPCs. beta-Catenin was selectively required for fetal HSPC competitiveness
      shortly after transplant, and protected cells from oxidative stress. Our results
      emphasize the complexity of Wnt signaling dynamics in HSPC maintenance and
      function.

PMID- 29345391
TI  - NPTX1 inhibits colon cancer cell proliferation through down-regulating cyclin A2
      and CDK2 expression.
AB  - Colon cancer is the third most common malignancy and one of the leading causes of
      cancer-associated mortality worldwide. Neuronal pentraxin 1 (NPTX1) is associated
      with tumor progression in some types of tumors. However, its expression and role
      in colon cancer has not been yet reported. Here we observed that NPTX1 was down
      regulated in colon cancer. Additionally, we explored the functional significance
      of NPTX1 in colon cancer. We found that over-expression of NPTX1 inhibited colon
      cancer cell growth by performing MTT, colony formation, Edu corporation assays,
      and cell cycle analysis. In vivo mouse experiments also confirmed the anti
      proliferative role of NPTX1 in colon cancer. Further mechanistic study showed
      that over-expression of NPTX1 inhibited the expression of cyclin A2 and CDK2 in
      colon cancer cells, thereby regulating the Rb-E2F signaling. In summary, these
      findings reveal that NPTX1 suppress the colon cancer cell growth and might serve
      as a useful potential target for treatment of colon cancer.

PMID- 29345392
TI  - Who May Benefit From On-Demand Control of Deep Brain Stimulation? Noninvasive
      Evaluation of Parkinson Patients.
AB  - BACKGROUND: In closed-loop on-demand control (ODC) of deep brain stimulation
      (DBS), stimulation is applied only when symptoms appear. Following stimulation of
      a fixed duration, DBS is switched off until the symptoms reappear. By repeating
      these demand-driven cycles, the amount of stimulation delivered can be decreased,
      thereby reducing DBS side-effects and improving battery-life of the pulse
      generator. This article introduces Ro metric for quantification of degree of
      benefit of ODC and explores candidate selection in tremor-dominant Parkinson's
      disease (PD). METHOD: The study was performed on nine PD patients previously
      implanted with Medtronic DBS systems. Accelerometer sensor was placed on the
      tremor-dominant hand to detect onset of tremor. Fixed duration of stimulation
      (DS) of 20-80 sec was applied. Once the tremor was observed, stimulation was
      switched on. These trials were repeated during resting, postural, and kinetic
      conditions. Ro metric was calculated as the ratio of stimulation-off tremor-free
      period to the DS. Ro calculated at different DS were compared for each patient.
      RESULTS: We found that for each patient, Ro varied with DS and an optimal DS*
      gave a higher percentage of stimulation-off time. Average Ro at DS* varied from
      0.554 to 4.24 for eight patients giving 35%-80% stimulation-off time.
      CONCLUSIONS: Ro values can be used for selection of optimal DS* in ODC. Three of
      nine patients were found to be tremor-free without stimulation for >50% of total
      time with even up to 80% in one patient. Patients with low Ro may not benefit
      from ODC in DBS, where the trade-off between having side-effects and using ODC
      system will need to be assessed.

PMID- 29345393
TI  - The Protective Effect of Spinal Cord Stimulation Postconditioning Against Spinal
      Cord Ischemia/Reperfusion Injury in Rabbits.
AB  - BACKGROUND: Delayed paraplegia due to spinal cord ischemia/reperfusion injury
      (IRI) remains one of the most severe complications of thoracoabdominal aneurysm
      surgery, for which effective prevention and treatment is still lacking.
      OBJECTIVES: The current study investigates whether spinal cord stimulation (SCS)
      postconditioning has neuroprotective effects against spinal cord IRI. METHOD:
      Ninety-six New Zealand white male rabbits were randomly divided into four groups
      as follows: a sham group and three experimental groups (C group, 2 Hz group, and
      50 Hz group) n = 24/group. Spinal cord ischemia was induced by transient
      infrarenal aortic balloon occlusion for 28 min, after which rabbits in group C
      underwent no additional intervention, while rabbits in the other two experimental
      groups underwent 2 Hz or 50 Hz epidural SCS for 30 min at the onset of
      reperfusion and then daily until sacrifice. Hind limb neurologic function of
      rabbits was assessed using Jacob scale. Lumbar spinal cords were harvested
      immediately after sacrifice for histological examination and terminal
      deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining.
      The number of viable alpha-motor neurons in ventral horn was counted and TUNEL
      positive rate of alpha-motor neurons was calculated. RESULT: Spinal cord IRI was
      caused by transient infrarenal aorta occlusion for 28 min. Both 2 Hz and 50 Hz
      SCS postconditioning had neuroprotective effects, particularly the 2 Hz SCS
      postconditioning. Comparing to C group and 50 Hz group, rabbits in the 2 Hz group
      demonstrated better hind limb motor function and a lower rate of TUNEL-positive
      alpha-motor neuron after eight hours, one day, three days, and seven days of
      spinal cord reperfusion. More viable alpha-motor neurons were preserved after one
      and three days of spinal cord reperfusion in 2 Hz group rabbits than in C group
      and 50 Hz group rabbits. CONCLUSION: SCS postconditioning at 2 Hz protected the
      spinal cord from IRI.

PMID- 29345394
TI  - Viruses as key modulators of the TGF-beta pathway; a double-edged sword involved
      in cancer.
AB  - Transforming growth factor-beta (TGF-beta) signaling pathway is a key network in
      cell signaling that controls vital processes such as proliferation,
      differentiation, apoptosis, epithelial-mesenchymal transition, and migration,
      thus acting as a double-edged sword in normal development and diseases, in
      particular organ fibrosis, vascular disorders, and cancer. Early in
      tumorigenesis, the pathway exerts anti-tumor effects through suppressing cell
      cycle and inducing apoptosis, while during late stages, it functions as a tumor
      promoter by enhancing tumor invasiveness and metastasis. This signaling pathway
      can be perturbed by environmental and genetic factors such as microbial
      interference and mutation, respectively. In this way, the present review
      describes the modulation of the TGF-beta pathway by oncogenic human viral
      pathogens and other viruses. The main mechanisms by which viruses interferes with
      TGF-beta signaling seems to be through (1) the alteration of either TGF-beta
      protein expression or activation, (2) the modulation of the TGF-beta receptors or
      SMADs factors (by interfering with their levels and functions), (3) the
      alteration of none-SMAD pathways, and (4) indirect interaction with the pathway
      by the modulation of transcriptional co-activator/repressor and regulators of the
      pathway. Given the axial role of this pathway in tumorigenesis, it can be
      regarded as an attractive target for cancer therapy. Hence, further
      investigations on this subject may represent molecular targets among either TGF
      beta signaling molecules or viral factors for the treatment and management of
      viral infection consequences such as cancer.

PMID- 29345395
TI  - Patient, carer and public involvement in major system change in acute stroke
      services: The construction of value.
AB  - BACKGROUND: Patient and public involvement is required where changes to care
      provided by the UK National Health Service are proposed. Yet involvement is
      characterized by ambiguity about its rationales, methods and impact. AIMS: To
      understand how patients and carers were involved in major system changes (MSCs)
      to the delivery of acute stroke care in 2 English cities, and what kinds of
      effects involvement was thought to produce. METHODS: Analysis of documents from
      both MSC projects, and retrospective in-depth interviews with 45 purposively
      selected individuals (providers, commissioners, third-sector employees) involved
      in the MSC. RESULTS: Involvement was enacted through consultation exercises; lay
      membership of governance structures; and elicitation of patient perspectives.
      Interviewees' views of involvement in these MSCs varied, reflecting different
      views of involvement per se, and of implicit quality criteria. The value of
      involvement lay not in its contribution to acute service redesign but in its
      facilitation of the changes developed by professionals. We propose 3 conceptual
      categories-agitation management, verification and substantiation-to identify
      types of process through which involvement was seen to facilitate system change.
      DISCUSSION: Involvement was seen to have strategic and intrinsic value. Its
      strategic value lay in facilitating the implementation of a model of care that
      aimed to deliver evidence-based care to all; its intrinsic value was in the idea
      of citizen participation in change processes as an end in its own right. The
      concept of value, rather than impact, may provide greater traction in analyses of
      contemporary involvement practices.

PMID- 29345396
TI  - Performance, rumen fermentation and blood metabolites of dairy calves fed starter
      mixtures supplemented with herbal plants, essential oils or monensin.
AB  - This study evaluated the supplementation effects of three herbal plants (thyme
      [THY], eucalyptus [EUC] and celery [CEL]), a commercial phytogenic additive
      containing essential oils (PFA-EO, Digestarom(r) P.E.P.) and monensin (MON) in
      calf starter on performance, rumen fermentation and blood metabolites during pre-
      (days 3-55) and post-weaning (days 56-70). Sixty-six Holstein dairy calves (3
      days of age, 41.2 +/- 3 kg of BW) were allocated to one of six starters
      supplemented with: (i) no additives (CON), (ii) MON (30 mg/kg), (iii) THY (23
      g/kg), (iv) CEL (23 g/kg), (v) EUC (23 g/kg) and (vi) PFA-EO (3 g/kg). All the
      calves were offered starters ad libitum plus 6 L of whole milk daily. Starter
      intake tended to be the highest in calves fed PFA-EO and THY; intermediate in
      calves fed CON, MON and EUC; and the lowest in those fed CEL. Average daily gain
      (ADG) and feed efficiency (FE) remained unaffected by dietary treatments during
      the pre-weaning. During the post-weaning period, ADG and FE were greatest in
      calves fed EUC followed by those fed CON, MON, PFA-EO and THY, and then in those
      fed CEL. No differences were observed among the treatments in skeletal growth,
      faecal score, rumen pH or ammonia-N concentration. Compared to calves fed CON and
      MON, those fed the herbal plants or PFA-EO tended to recorded higher molar
      proportions of acetate and butyrate, and the acetate: propionate ratio. Blood
      malondialdehyde level did not differ among treatments, but calves on CON had the
      highest glucose concentration, and those fed PFA-EO recorded the highest value
      for beta-hydroxyl butyrate on day 70. In conclusion, the results indicate that
      the three herbs and PFA-EO are capable of modulating some of the rumen
      fermentation parameters and blood metabolites as well as eucalyptus could
      potentially be a better alternative to monensin for improving post-weaning
      performance.

PMID- 29345397
TI  - Characteristics of patients who progress from bridging to long-term oxygen
      therapy.
AB  - BACKGROUND: Patients with persistent hypoxia following an acute hospital
      admission may be discharged with 'bridging' domiciliary oxygen as per criteria
      defined by the Thoracic Society of Australia and New Zealand. The need for
      continuous long-term oxygen therapy (LTOT) is then reassessed at a clinic review
      1-2 months later. AIM: To describe the characteristics of patients discharged
      from an acute hospital admission with continuous short-term oxygen therapy
      (STOT), and subsequently to investigate for differences between subjects who
      proceeded to qualify for continuous LTOT versus those who were able to cease STOT
      at review. METHODS: This is a retrospective cohort study involving all subjects
      discharged from Alfred Health between 2011 and 2015 inclusive with bridging
      domiciliary oxygen. Multiple biochemical, physiological and demographic
      characteristics were collated and analysed. RESULTS: Of all patients prescribed
      continuous STOT at time of discharge, 47.3% qualified for LTOT at outpatient
      review. This cohort had a significantly lower PaO2 measurement at time of
      discharge, compared with those who no longer qualified. CONCLUSION: PaO2 at time
      of discharge provides a signal with the potential to identify who will require
      continuous LTOT following an acute hospital admission. Additionally, this study
      highlights the need to re-evaluate patients' oxygen requirements during a period
      of clinical stability.

PMID- 29345398
TI  - Music reduces state anxiety scores in patients undergoing pleural procedures: a
      randomised controlled trial.
AB  - BACKGROUND: Patient anxiety is an often overlooked complication of pleural
      diagnostic and therapeutic procedures. Listening to music is effective in
      reducing patient anxiety in some endoscopy procedures but has not yet been
      evaluated in pleural procedures. AIM: To evaluate the benefits of music therapy
      during pleural procedures on a patient's anxiety, perceived pain and satisfaction
      with the procedure. METHODS: Consecutive patients undergoing therapeutic pleural
      procedures were randomised to music and control groups. Participants in the music
      group listened to self-selected music using ear-bud headphones for the duration
      of the procedure. State anxiety was assessed before and after the procedure using
      the State Trait Anxiety Inventory. Physiological parameters were also measured.
      RESULTS: Sixty patients were included in the study. In the music group, a
      reduction in state anxiety scores were observed post-procedure (34 +/- 11 vs 48
      +/- 13, P < 0.001), while no change was observed in the control group (40 +/- 11
      vs 42 +/- 11, P = 0.51). Participants in the music group had reductions in heart
      rate (87 +/- 17 vs 95 +/- 15, P = 0.04), systolic (121 +/- 13 vs 130 +/- 16, P =
      0.02) and diastolic blood pressure (72 +/- 8 vs 78 +/- 9, P = 0.01) post
      procedure compared to the pre-procedures values. A similar change was not
      detected in the control group: heart rate (86 +/- 17 vs 85 +/- 15, P = 0.73),
      systolic (133 +/- 21 vs 134 +/- 20, P = 0.83) and diastolic blood pressure (77 +/
      9 vs 79 +/- 10, P = 0.30). There was no difference in patient pain scores (P =
      0.8), willingness to undergo the procedure again (P= 0.27), satisfaction with the
      performance of the pleural procedure (P = 0.20) and duration of the procedure (P
      = 0.68) between the music and control groups. CONCLUSIONS: Listening to music
      appears to be beneficial in reducing anxiety in patients undergoing pleural
      procedures.

PMID- 29345399
TI  - Glycine improves the remodeling process of tenocytes in vitro.
AB  - Tendinitis changes the biochemical and morphological properties of the tendon,
      promoting an increase of activity of metalloproteinases and disorganization of
      collagen bundles. Tenocytes, the primary cells in tendon, are scattered
      throughout the collagenic fibers, and are responsible of tendon remodeling and
      tissue repair in pathological condition. In vivo, glycine, component of the
      typical Gly-X-Y collagen tripeptide, showed beneficial effects in biochemical and
      biomechanical properties of Achilles tendon with tendinitis. In this study, we
      analyzed the effect of glycine in tenocytes subjected to inflammation. Tenocytes
      from Achilles tendon of rats were treated with TNF-alpha (10 ng/mL) with and
      without previous treatment with glycine (20 mM). Cell proliferation and migration
      were evaluated, as well as the expression of matrix molecules such as
      glycosaminoglycans, metalloproteinases (MMPs), TIMPs, and collagen I. Glycine can
      revert the inflammation due to the action of TNF-alpha by controlling the MMPs
      quantity and activity. These data indicated that the molecules involved to
      remodeling process of extracellular matrix are modulated both by TNF-alpha and
      the availability of collagen precursors; in fact, this study indicates the
      glycine can be useful for treatment of inflammation and for modulating tenocytes
      metabolism in tendons.

PMID- 29345400
TI  - Fludrocortisone-a treatment for tubulopathy post-paediatric renal
      transplantation: A national paediatric nephrology unit experience.
AB  - Calcineurin inhibitors post-renal transplantation are recognized to cause
      tubulopathies in the form of hyponatremia, hyperkalemia, and acidosis. Sodium
      supplementation may be required, increasing medication burden and potentially
      resulting in poor compliance. Fludrocortisone has been beneficial in addressing
      tubulopathies in adult studies, with limited paediatric data available. A
      retrospective review of data from an electronic renal database from December 2014
      to January 2016 was carried out. Forty-seven post-transplant patients were
      reviewed with 23 (49%) patients on sodium chloride or bicarbonate. Nine patients,
      aged 8.3 years (range 4.9-16.4), commenced fludrocortisone 22 months (range 1-80)
      after transplant and were followed up for 9 months (range 2-20). All patients
      stopped sodium bicarbonate; all had a reduction or no increase in total daily
      doses of sodium chloride. Potassium levels were significantly lower on
      fludrocortisone, 5.2 vs 4.5 mmol/L, P = .04. No difference was noted in renal
      function (eGFR 77.8 vs 81.7 mL/min/1.73 m2 , P = .45) and no significant increase
      in systolic blood pressure (z-scores 0.99 vs 0.85, P = .92). No side effects
      secondary to treatment with fludrocortisone were reported. A significant
      proportion of renal transplant patients were on sodium supplementation and
      fludrocortisone reduced sodium supplementation without significant effects on
      renal function or blood pressure. Fludrocortisone appears to be safe and
      effective for tubulopathies in children post-transplantation.

PMID- 29345401
TI  - Are characteristics of abdominal pain helpful to identify patients with visceral
      hypersensitivity in irritable bowel syndrome? Results of a prospective study.
AB  - BACKGROUND: Some consider that patients with visceral hypersensitivity may
      represent a separate entity within the IBS population not only from a
      pathophysiological but also from a clinical perspective. The aim of this
      prospective exploratory study was to assess whether characteristics of abdominal
      pain in IBS patients could be suggestive of hypersensitivity. METHODS: This
      prospective study included consecutive IBS patients selected by Rome III
      criteria. Validated scores (IBS-SSS, Bristol stool scale, HADS) were used to
      phenotype patients who were also asked to describe the main location of their
      abdominal pain on a simple image (abdomen divided into 6 zones). Progressive
      isobaric rectal distensions were performed to demonstrate, with the ascending
      method of limits, allodynia (pain threshold lower than 24 mmHg). KEY RESULTS:
      Fifty patients (women: 72%), 42.6 +/- 15.7 years old, were included. Sub-types
      were IBS-D, IBS-C and IBS-M in 58%, 22% and 20% of cases, respectively. Allodynia
      was present in 18% of cases. Neither IBS-SSS nor intensity of pain was predictive
      of hypersensitivity. In hypersensitive patients, pain was more often located in
      one of the two iliac fossa (P = 0.02) and located outside these areas in only 11%
      of cases. The sensitivity and the specificity of this pain location to
      differentiate hyper from normosensitive patients were 0.89 and 0.59,
      respectively. CONCLUSIONS & INFERENCES: The location of pain is different between
      hyper and normosensitive IBS patients. Pain located outside one of the two iliac
      fossa suggests that the patient is normosensitive.

PMID- 29345402
TI  - Association of long-term glycaemic control on tear break-up times and dry eye
      symptoms in Chinese patients with type 2 diabetes.
AB  - IMPORTANCE: Diabetes mellitus is known to be associated with dry eye syndrome
      (DES), but the effects of long-term glycaemic control on tear film metrics and
      dry eye symptoms are not known in the Chinese population. BACKGROUND: To evaluate
      tear film stability and dry eye symptoms and their associations with systemic
      risk factors in Chinese patients with type 2 diabetes mellitus (T2DM). DESIGN:
      Cross-sectional study set at the Lo Fong Siu Po Eye Centre (Grantham Hospital),
      Hong Kong. PARTICIPANTS: A total of 80 Chinese participants, aged 18 or above,
      with T2DM recruited from the specialist outpatient setting were included.
      METHODS: The Oculus Keratograph 5M (Oculus Inc., Wetzlar, Germany) was used to
      measure the non-invasive tear break-up time (NITBUT). Ocular symptoms were
      evaluated using the Ocular Surface Disease Index (OSDI). The association between
      OSDI, NITBUT and metabolic parameters relating to diabetes were evaluated using
      multiple linear regression. MAIN OUTCOME MEASURES: The associations between long
      term glycaemic control and NITBUT and OSDI scores. RESULTS: Stepwise multiple
      linear regression analysis revealed glycated haemoglobin to be the only
      significant independent variable for NITBUT (R2 = 0.099, P = 0.014) and OSDI (R2
      = 0.062, P = 0.044) after controlling for potential confounders. The age-adjusted
      prevalence of DES was 20% (95% confidence interval: 11-30%) in the Chinese T2DM
      population. The odds of DES for increasing percentage of glycated haemoglobin was
      1.49 (95% confidence interval: 1.03-2.17, P = 0.04). CONCLUSIONS AND RELEVANCE:
      Our findings highlight the importance of good glycaemic control as a modifiable
      risk factor for both dry eye symptoms and tear film instability in patients with
      T2DM.

PMID- 29345403
TI  - Improving patient adherence to secondary prevention medications 6 months after an
      acute coronary syndrome: observational cohort study.
AB  - BACKGROUND: Most patients are recommended secondary prevention pharmacotherapies
      following an acute coronary syndromes (ACS). AIM: To identify predictors of
      adherence at 6 months and strategies to improve adherence to these therapies.
      METHODS: Patients in the CONCORDANCE registry who were discharged on evidence
      based medications were stratified into those receiving >=75% ('adherent') or <75%
      ('non-adherent') of indicated medications at 6 months. Baseline characteristics,
      hospital and post-discharge care were compared between groups. Multivariable
      logistic analysis identified independent predictors of adherence. The relative
      contribution of each clinical or treatment factor to 'adherence' was determined
      using an adequacy measure method. RESULTS: Follow-up data were available for 6595
      patients, 4492 (68.1%) of whom were 'adherent'. Clinical factors predictive of
      adherence included previous stroke, percutaneous coronary intervention (PCI) and
      hypertension (odds ratios (OR) 1.36-1.56); factors predictive of non-adherence
      included discharge diagnosis of non-ST-segment elevation myocardial infarction
      (vs unstable angina) (OR 0.51) and atrial fibrillation (OR 0.59). Discharge on
      >=75% of indicated medications was a strong predictor of adherence at 6 months
      (OR 10.23, 95% confidence interval 7.89-13.27); in-hospital management factors
      predicting non-adherence were medical management alone (OR 0.34) and coronary
      artery bypass graft (OR 0.50) (both vs PCI). Post-discharge predictors of
      adherence included cardiac rehabilitation (OR 1.36) and general practitioner
      attendance (OR 1.40). CONCLUSION: Failure to discharge patients on indicated
      therapies is the most important modifiable predictor of adherence failure 6
      months after an ACS. Implementing protocols to automate prescription of indicated
      discharge therapies, has the potential to reduce non-adherence dramatically in
      the 6 months following discharge.

PMID- 29345404
TI  - Individual variability in response to renin angiotensin aldosterone system
      inhibition predicts cardiovascular outcome in patients with type 2 diabetes: A
      primary care cohort study.
AB  - AIMS: To assess variability in systolic blood pressure (SBP) and albuminuria
      (urinary albumin creatinine ratio [UACR]) responses in patients with type 2
      diabetes mellitus initiating renin angiotensin aldosterone system (RAAS)
      inhibition, and to assess the association of response variability with
      cardiovascular outcomes. MATERIAL AND METHODS: We performed an observational
      cohort study in patients with type 2 diabetes who started RAAS inhibition between
      2007 and 2013 (n = 1600). Patients were identified from general practices in the
      Netherlands. Individual response in SBP and UACR was assessed during 15 months'
      follow-up. Patients were categorized as: good responders (?SBP <0 mm Hg and ?UACR
      <0%); intermediate responders (?SBP <0 mm Hg and ?UACR >0% or ?SBP >0 mm Hg and
      ?UACR <0%); or poor responders (?SBP >0 mm Hg and ?UACR >0%). Multivariable Cox
      regression was performed to test the association between initial RAAS inhibition
      response and subsequent cardiovascular outcomes. RESULTS: After starting RAAS
      inhibition, the mean SBP change was -13.2 mm Hg and the median UACR was -36.6%,
      with large between-individual variability, both in SBP [5th to 95th percentile:
      48.5-20] and UACR [5th to 95th percentile: -87.6 to 171.4]. In all, 812 patients
      (51%) were good responders, 353 (22%) had a good SBP but poor UACR response, 268
      (17%) had a good UACR but poor SBP response, and 167 patients (10%) were poor
      responders. Good responders had a lower risk of cardiovascular events than poor
      responders (hazard ratio 0.51, 95% confidence interval 0.30-0.86; P = .012).
      CONCLUSIONS: SBP and UACR response after RAAS inhibition initiation varied
      between and within individual patients with type 2 diabetes treated in primary
      care. Poor responders had the highest risk of cardiovascular events, therefore,
      more efforts are needed to develop personalized treatment plans for these
      patients.

PMID- 29345405
TI  - Abdominal paracentesis: use of a standardised procedure checklist and equipment
      kit improves procedural quality and reduces complications.
AB  - BACKGROUND: Paracentesis is a common invasive procedure performed by junior
      doctors. Audit of procedure conduct at two New Zealand hospitals in 2012 revealed
      poor performance across a range of quality measures, including documentation of
      informed consent, excessive catheter dwell times and inappropriate albumin
      prescription. Complication rates were 12.7%, compared with published rates of
      around 9%. A local procedure protocol did not exist. AIM: To evaluate the effect
      of a standardised procedure checklist (PC) and equipment kit (EK) on procedural
      quality and complication rates for abdominal paracentesis. METHODS: After
      presenting the 2012 audit results to resident doctors, we reviewed the
      paracentesis literature and developed a local procedure protocol (PC and EK).
      These tools were made readily available after an education campaign. Paracenteses
      performed after the intervention were studied to determine the impact on
      procedural quality and safety. RESULTS: Seventy-four paracenteses (14 diagnostic;
      60 therapeutic) were performed in 10 months after the introduction of PC and EK.
      Significant improvements were observed with the use of PC including documentation
      of informed consent (97% vs 74%, P = <0.01) and aseptic technique (100% vs 62%, P
      = <0.01). Catheter dwell times <6 h improved (72% vs 48%, P = 0.02).
      Inappropriate albumin prescriptions were less frequent (21% vs 66%, P = <0.01).
      Complication rates decreased from 12.7% to 2.8% (P = <0.01). CONCLUSIONS: The PC
      and EK improved rates of informed consent, appropriate documentation and protocol
      adherence. Significantly fewer procedure-related complications occurred after
      introduction of these tools.

PMID- 29345406
TI  - Helicobacter pylori infection and occurrence of celiac disease in subjects HLA
      DQ2/DQ8 positive: A prospective study.
AB  - BACKGROUND: Celiac disease (CD) occurs in subjects positive for HLA-DQ2 and/or
      DQ8 gene loci at any age following ingestion of gluten-containing food. An
      increased permeability of the mucosa allows interactions between gliadin
      macromolecules and genetic factors. It has been observed that Helicobacter pylori
      has the ability to modulate the integrity of the duodenal epithelium. We aimed to
      determine whether H. pylori infection may enhance the occurrence of CD in
      genetically susceptible subjects. MATERIALS AND METHODS: This was a prospective
      observational study. Patients undergoing upper endoscopy for any reason and
      positive for HLA-DQ2 and/or DQ8 haplotypes with or without CD were included. H.
      pylori infection was defined as a positive gastric histopathology and/or 13C-urea
      breath test. Prevalence of infection was compared between enrolled subjects with
      and without CD. Multiple logistic regression analysis, adjusting odds ratios for
      patient age, gender, smoking habit, residency, body mass index, and assumption of
      nonsteroidal anti-inflammatory drugs (NSAIDs) and proton-pump inhibitors (PPIs)
      were performed. RESULTS: A total of 397 genetically susceptible individuals (mean
      age: 37.7 +/- 15.3 years; 86% women) were enrolled between October 2014 and
      October 2017. There were 265 (68%) patients with a diagnosis of CD. Overall, the
      prevalence of H. pylori infection was 33% and was similar in patients with and
      without CD (32% vs 36%). Adjustment for all covariates did not reveal any
      significant association, although adjusted odds ratio (OR) for CD was higher in
      female (OR = 1.302), in patients H. pylori positive (OR = 1.277), followed by use
      of NSAIDs (OR = 1.126), respectively. The use of PPIs appeared to be mildly
      protective against CD (OR = 0.644). CONCLUSION: Our study did not reveal any
      significant relationship between H. pylori and CD risk, even taking into account
      other confounders. More importantly, our findings do not support a "protective"
      role of H. pylori infection against CD, as previously reported. Therefore, there
      are no reasons to avoid eradication of H. pylori also in subject genetically
      susceptible for CD.

PMID- 29345407
TI  - Hepatitis C eradication with DAA and risk of liver cancer recurrence: The debate
      unrests.

PMID- 29345408
TI  - The effect of eradication of Helicobacter pylori on gastric cancer prevention in
      healthy asymptomatic populations.
AB  - BACKGROUND: Although many epidemiologic studies have evaluated the effect of
      Helicobacter pylori eradication on gastric cancer, the effect is still uncertain
      in general populations. We evaluated whether H. pylori eradication would affect
      the incidence of gastric cancer in healthy asymptomatic populations. MATERIALS
      AND METHODS: We performed a retrospective cohort study in 38 984 asymptomatic
      individuals, who underwent health screening examinations more than twice between
      2005 and 2016. We investigated the incidence of gastric cancer among 3 groups:
      those without H. pylori infection (Hp-negative group), those with H. pylori
      eradication (eradication group), and those without H. pylori eradication (non
      eradication group). RESULTS: The cumulative incidence of gastric cancer was 54.5
      cases per 100 000 person-years during a median of 6.4 years. In a multivariate
      analysis using the Cox proportional hazard model, the cumulative incidence of
      gastric cancer in the non-eradication group was significantly higher than those
      in the Hp-negative (hazard ratio [HR] 4.12, P < .001) and eradication groups (HR
      2.73, P = .001). However, the cumulative incidence of gastric cancer was not
      significantly different between the eradication and Hp-negative groups. Other
      risk factors for gastric cancer occurrence were age, smoking, family history of
      gastric cancer, and gastric atrophy. The standardized incidence ratios of the age
      groups above 40 and below 70 in the eradication group were all significantly
      decreased. CONCLUSIONS: Helicobacter pylori eradication reduced the cumulative
      incidence of gastric cancer in healthy asymptomatic population, and the effect of
      H. pylori eradication on the prevention of gastric cancer was observed in all
      ages.

PMID- 29345409
TI  - How I investigate monocytosis.
AB  - Monocytosis is a common finding that is caused by a wide variety of neoplastic
      and non-neoplastic conditions. The adequate evaluation of monocytosis involves
      the integration of laboratory data, morphology, clinical findings, and the
      judicious use of ancillary studies. We review the literature on monocytosis,
      including the 2017 revised 4th edition of the World Health Organization
      classification of hematopoietic neoplasms. We present a review of monocytosis
      with practical guidelines on how to approach both routine and challenging cases.

PMID- 29345410
TI  - High-Resolution Three-Dimensional Computed Tomography Reconstruction as First
      Line Imaging Modality to Detect Intrathecal Catheter Malfunction.

PMID- 29345411
TI  - Ethnicity, socioeconomic status and the severity and course of non-cystic
      fibrosis bronchiectasis.
AB  - BACKGROUND AND AIMS: This study evaluated whether there are ethnic factors which
      affect the severity and progression of bronchiectasis in our adult multi-ethnic
      population in Auckland, New Zealand. METHODS: Clinical records were reviewed from
      patients attending the outpatient facilities of our institution between 2007 and
      2010. Data collected included demographics, clinical features, smoking status,
      self-reported ethnicity, socioeconomic status (NZDep), pulmonary function and
      sputum microbiology. RESULTS: A total of 437 patients was identified: median age
      65 years, 66% female, mean forced expiratory volume in the first second (FEV1 )
      62.4% predicted, and 10.5% of patients had recurrent growth of Pseudomonas
      aeruginosa. Patients of Maori and Pacific ethnicity were overrepresented compared
      to the institution population catchment and had more severe impairment of lung
      function: mean % predicted FEV1 for Pacific 52.0, Maori 58.6, European 68.6,
      Asian 64.2 (P < 0.0001). This was independent of socioeconomic status. However,
      no overall decline was seen in serial lung function measurements, either across
      the whole cohort or in any particular ethnic group. CONCLUSIONS: Patients of
      Maori and Pacific ethnicity are both overrepresented and have more severe
      bronchiectasis in this cohort, independent of socioeconomic status. Ethnicity did
      not predict decline in pulmonary function. Further studies into genetic
      predisposition to bronchiectasis in Maori or Pacific people may be warranted.

PMID- 29345412
TI  - WNT5A promotes migration and invasion of human osteosarcoma cells via SRC/ERK/MMP
      14 pathway.
AB  - WNT5A, a representative ligand of activating several non-canonical WNT signal
      pathways, plays significant roles in oncogenesis and tumor inhibition. It has
      been shown that the non-receptor tyrosine kinase SRC is required for WNT5A
      induced invasion of osteosarcoma cells. However, the precise molecular mechanism
      underlying WNT5A/SRC-mediated osteosarcoma cells invasion remains poorly defined.
      The study was designed to explore the role of ERK1/2 in WNT5A/SRC-induced
      osteosarcoma cells invasion and the downstream target of the SRC/ERK1/2
      signalings. We found that WNT5A (100 ng/mL) remarkably stimulated migration and
      invasion of human osteosarcoma MG-63 cells, whereas inhibiting either SRC kinase
      activity by siRNA-mediated SRC silence or ERK1/2 phosphorylation by PD98059
      treatment suppressed these effects, which suggested that the activation of SRC
      and ERK1/2 is essential for WNT5A-induced MG-63 cells migration and invasion.
      Furthermore, ERK1/2 phosphorylation induced by WNT5A was dramatically blocked by
      SRC siRNA. Additionally, our study further demonstrated that MMP-14 was
      upregulated after exposure to WNT5A in MG-63 cells, and the increased expression
      was blocked by SRC siRNA or PD98059. Collectively, these results indicate that
      WNT5A activates SRC/ERK1/2 signal pathway, leading to the upregulation of MMP-14
      expression and MG-63 cells migration and invasion.

PMID- 29345413
TI  - Hepatitis B screening before rituximab therapy: a multicentre South Australian
      study of adherence.
AB  - BACKGROUND: International guidelines recommend screening for hepatitis B virus
      (HBV) infection prior to administration of rituximab, due to high risk of HBV
      reactivation in at-risk patients. AIMS: To determine: (i) adherence to the South
      Australian (SA) protocol for HBV screening; (ii) HBV prevalence in patients
      receiving rituximab; and (iii) outcomes of patients at risk of HBV reactivation.
      METHODS: All patients commenced on rituximab at the six major SA public hospitals
      during a 12-month period were included in the study. Adherence was assessed by
      documentation of both hepatitis B surface antigen (HBsAg) and hepatitis B core
      antibody (HBcAb) prior to initiation of rituximab. Patients were observed for a
      minimum of 6 months following rituximab initiation. RESULTS: Four hundred and
      thirty eight patients were included in the study. The main indication for
      rituximab therapy was haematological malignancy (76.0%). Two hundred and nine
      (47.7%) failed to receive appropriate HBV screening, 86 (19.6%) had neither HBsAg
      nor HBcAb performed, and 119 (27.2%) had only HBsAg performed. The identified
      prevalence of at-risk cases (either HBsAg- or HBcAb-positive) within the study
      population was 4.6% (20/438 cases). One case of HBV reactivation was identified,
      but none led to acute liver failure, transplantation or death. CONCLUSIONS: Poor
      adherence to HBV screening protocols suggests the need for targeted clinician
      education and system redesign. While the rate of reactivation was low, the
      prevalence of at-risk patients in this population was high and justifies further
      initiatives to increase adherence rates to HBV screening pre-rituximab.

PMID- 29345414
TI  - Molecular characterization of a series of 990 index patients with albinism.
AB  - Albinism is a clinically and genetically heterogeneous disease characterized by
      variable degrees of hypopigmentation and by nystagmus, foveal hypoplasia, and
      chiasmatic misrouting of the optic nerves. The wide phenotypic heterogeneity
      impedes the establishment of phenotype-genotype correlations. To obtain a precise
      diagnosis, we screened the 19 known albinism genes in 990 index patients using
      targeted next-generation sequencing (NGS) and high-resolution comparative genomic
      hybridization. A molecular diagnosis was obtained in 72.32% of patients. A total
      of 243 new pathogenic variants were identified. Intragenic rearrangements
      represented 10.8% of all pathogenic alleles. NGS panel analysis allowed
      establishing a diagnosis for the rarest forms of the disease, which could not be
      diagnosed otherwise. Because of the clinical overlap between the different forms
      of the disease, diagnosis nowadays clearly relies on molecular grounds.

PMID- 29345415
TI  - Investigating Complications Associated With Occipital Nerve Stimulation: A MAUDE
      Study.
AB  - OBJECTIVES: The objectives of this study are to utilize the MAUDE data base to
      enhance our understanding of the complication profile for Occipital Nerve
      Stimulation, a therapy for which the current level of evidence is limited.
      Additionally, it is our objective to describe a systematic approach to processing
      the MAUDE data, which addresses its flaws and enhances its utility. METHODS: From
      the FDA website, we accessed adverse events reports from the MAUDE data base for
      devices used in Occipital Nerve Stimulation between June 30, 2007 and June 30,
      2017. All reports were sorted into an overall classification for types of adverse
      events, types of patient complaints, and types of specific device-related
      complications. We then evaluated for the total number of adverse event reports
      that contained each of the patient complains and device-related complications.
      RESULTS: A total of 1233 adverse event records were obtained. Eight hundred
      twenty-two records were classified as surgically manageable post-operative
      complications, 121 as device malfunction, 29 as patient compliance issues, and 27
      as intra-operative complications. Two hundred thirty-seven records were not
      classified. A total of 683 records contained patient complaints including 467
      complaints of ineffective stimulation, 122 complaints of inappropriate or over
      stimulation, 50 complaints of device-shock, and 44 complaints of IPG site pain.
      We found 581 post-operative device-related complications, which included 206
      instances of lead migration, 157 reports of lead erosion, 155 infections, 46 lead
      fractures, and 17 lead disconnections. CONCLUSION: The MAUDE data base is a
      useful tool to investigate device related complications and helps fill the
      current gap in ONS data. Reviewing the types and frequencies of complications
      reported over the years allows clinicians with less personal experience to have a
      more realistic expectation of complications and make informed decisions based on
      the patient's unique needs. Additionally, patient complaint data are useful in
      establishing more realistic expectations for patient outcomes.

PMID- 29345416
TI  - A qualitative study: experiences of stigma by people with mental health problems.
AB  - OBJECTIVES: Prior research has examined various components involved in the impact
      of public and internalized stigma on people with mental health problems. However,
      studies have not previously investigated the subjective experiences of mental
      health stigma by those affected in a non-statutory treatment-seeking population.
      DESIGN: An in-depth qualitative study was conducted using thematic analysis to
      investigate the experiences of stigma in people with mental health problems.
      METHODS: Eligible participants were recruited through a local mental health
      charity in the North West of England. The topic of stigma was examined using two
      focus groups of thirteen people with experience of mental health problems and
      stigma. RESULTS: Two main themes and five subthemes were identified. Participants
      believed that (1) the 'hierarchy of labels' has a profound cyclical impact on
      several levels of society: people who experience mental health problems, their
      friends and family, and institutional stigma. Furthermore, participants suggested
      (2) ways in which they have developed psychological resilience towards mental
      health stigma. CONCLUSIONS: It is essential to utilize the views and experiences
      gained in this study to aid understanding and, therefore, develop ways to reduce
      the negative impact of public and internal stigma. PRACTITIONER POINTS: People
      referred to their mental health diagnosis as a label and associated that label
      with stigmatizing views. Promote awareness and develop improved strategies (e.g.,
      training) to tackle the cyclical impact of the 'hierarchy of labels' on people
      with mental health problems, their friends and family, and institutional stigma.
      Ensure the implementation of clinical guidelines in providing peer support to
      help people to combat feeling stigmatized. Talking about mental health in
      psychological therapy or health care professional training helped people to take
      control and develop psychological resilience.

PMID- 29345417
TI  - Catheter-based edge-to-edge mitral valve repair for pulmonary pressure reduction
      and to postpone heart transplantation in a teenaged patient.
AB  - We report a case of catheter-based edge-to-edge mitral valve repair in a teenage
      male patient with non-ischaemic cardiomyopathy to improve pulmonary hypertension
      secondary to severe functional mitral regurgitation (FMR) to defer anticipated
      heart transplantation. A 19-year-old patient with previous history of fulminant
      myocarditis followed by markedly left ventricular dysfunction presented with
      severe mitral regurgitation 3 years after initial recovery. Slightly over time,
      deterioration of FMR was associated with gradual increase in pulmonary artery
      pressures despite optimal medical therapy. MitraClip implantation in this young
      patient was successfully performed with sustainable improvement of pulmonary
      hypertension.

PMID- 29345418
TI  - Welcome to the New Editorial Board Members.
AB  - We warmly welcome our new Editorial Board members Matthias Bickelhaupt, Sally
      Brooker, Xiaoming Feng, Mikiko Sodeoka, and Takafumi Ueno.

PMID- 29345419
TI  - Targeting the BCL2 Gene Promoter G-Quadruplex with a New Class of
      Furopyridazinone-Based Molecules.
AB  - Targeting of G-quadruplex-forming DNA in the BCL2 gene promoter to inhibit the
      expression of anti-apoptotic Bcl-2 protein is an attractive approach to cancer
      treatment. So far, efforts made in the discovery of molecules that are able to
      target the BCL2 G-quadruplex have succeeded mainly in the identification of
      ligands with poor drug-like properties. Here, a small series of furo[2,3
      d]pyridazin-4(5H)-one derivatives were evaluated as a new class of drug-like G
      quadruplex-targeting compounds. Biophysical studies showed that two derivatives
      could effectively bind to BCL2 G-quadruplex with good selectivity. Moreover, one
      such ligand was found to appreciably inhibit BCL2 gene transcription, with a
      substantial decrease in protein expression levels, and also showed significant
      cytotoxicity toward the Jurkat human T-lymphoblastoid cell line.

PMID- 29345420
TI  - Integration of Gas Enhanced Oil Recovery in Multiphase Fermentations for the
      Microbial Production of Fuels and Chemicals.
AB  - In multiphase fermentations where the product forms a second liquid phase or
      where solvents are added for product extraction, turbulent conditions disperse
      the oil phase as droplets. Surface-active components (SACs) present in the
      fermentation broth can stabilize the product droplets thus forming an emulsion.
      Breaking this emulsion increases process complexity and consequently the
      production cost. In previous works, it has been proposed to promote
      demulsification of oil/supernatant emulsions in an off-line batch bubble column
      operating at low gas flow rate. The aim of this study is to test the performance
      of this recovery method integrated to a fermentation, allowing for continuous
      removal of the oil phase. A 500 mL bubble column is successfully integrated with
      a 2 L reactor during 24 h without affecting cell growth or cell viability.
      However, higher levels of surfactants and emulsion stability are measured in the
      integrated system compared to a base case, reducing its capacity for oil
      recovery. This is related to release of SACs due to cellular stress when
      circulating through the recovery column. Therefore, it is concluded that the gas
      bubble-induced oil recovery method allows for oil separation and cell recycling
      without compromising fermentation performance; however, tuning of the column
      parameters considering increased levels of SACs due to cellular stress is
      required for improving oil recovery.

PMID- 29345421
TI  - Synthesis of Histidine-Containing Oligopeptides via Histidine-Promoted Peptide
      Ligation.
AB  - Histidine-containing peptides are valuable therapeutic agents for a treatment of
      neurodegenerative diseases. However, the synthesis of histidine-containing
      peptides is not trivial due to the potential of imidazole sidechain of histidine
      to act as a nucleophile if unprotected. A peptide ligation method utilizing the
      imidazole sidechain of histidine has been developed. The key imidazolate
      intermediate that acts as an internal acyl transfer catalyst during ligation is
      generated by deprotonation. Transesterification with amino acids or peptides
      tethered with C-terminal thioester followed by N->N acyl shifts led to the final
      ligated products. A range of histidine-containing dipeptides could be synthesized
      in moderate to good yields via this method without protecting the imidazole
      sidechain. The protocol was further extended to tripeptide synthesis via a long
      range N->N acyl transfer, and tetrapeptide synthesis.

PMID- 29345422
TI  - Cantharidic acid induces apoptosis of human leukemic HL-60 cells via c-Jun N
      terminal kinase-regulated caspase-8/-9/-3 activation pathway.
AB  - Cantharidin, a natural toxin from blister beetles, has shown potent anticancer
      activities on many solid tumor cells. Recently, cantharidin and its analogue,
      norcantharidin, were also shown to suppress nonsolid tumors such as chronic
      myeloid leukemia, acute myeloid leukemia (AML), and leukemic stem cells. However,
      there is no available information to address the effects of cantharidic acid
      (CAC), a hydrolysis product of cantharidin, on human AML cells. The present study
      showed that CAC, at a range of concentrations (0-20 MUM), concentration
      dependently inhibited cell proliferation in the HL-60 AML cell line. Western blot
      and flow cytometric assays demonstrated that CAC induced several features of
      apoptosis such as sub G1-phase cell increase, phosphatidylserine (PS)
      externalization, and significantly activated proapoptotic signaling including
      caspase-8, -9, and -3 activation and poly(ADP-ribose) polymerase (PARP) cleavage
      in HL-60 AML cells. Moreover, treatment of HL-60 cells with CAC induced
      concentration- and time- dependent activation of p38 mitogen-activated protein
      kinase (p38 MAPK) and c-Jun N-terminal kinase (JNK). Only JNK-, but not p38 MAPK
      specific inhibitor can reverse the CAC-induced activation of the caspase-8, -9,
      and -3. We concluded that CAC can induce apoptosis in human leukemic HL-60 cells
      via a caspases-dependent pathway, and that the apoptosis-inducing effect of CAC
      can be regulated by JNK activation signaling.

PMID- 29345423
TI  - Deep Eutectic Solvent Aqueous Solutions as Efficient Media for the Solubilization
      of Hardwood Xylans.
AB  - This work contributes to the development of integrated lignocellulosic-based
      biorefineries by the pioneering exploitation of hardwood xylans by solubilization
      and extraction in deep eutectic solvents (DES). DES formed by choline chloride
      and urea or acetic acid were initially evaluated as solvents for commercial xylan
      as a model compound. The effects of temperature, molar ratio, and concentration
      of the DES aqueous solutions were evaluated and optimized by using a response
      surface methodology. The results obtained demonstrated the potential of these
      solvents, with 328.23 g L-1 of xylan solubilization using 66.7 wt % DES in water
      at 80  degrees C. Furthermore, xylans could be recovered by precipitation from
      the DES aqueous media in yields above 90 %. The detailed characterization of the
      xylans recovered after solubilization in aqueous DES demonstrated that 4-O-methyl
      groups were eliminated from the 4-O-methylglucuronic acids moieties and uronic
      acids (15 %) were cleaved from the xylan backbone during this process. The
      similar Mw values of both pristine and recovered xylans confirmed the success of
      the reported procedure. DES recovery in four additional extraction cycles was
      also demonstrated. Finally, the successful extraction of xylans from Eucalyptus
      globulus wood by using aqueous solutions of DES was demonstrated.

PMID- 29345424
TI  - A Fluorescence-Based Sensor Assay that Monitors General Protein Aggregation in
      Human Cells.
AB  - Protein conformational disorders are characterized by disruption of protein
      folding and toxic accumulation of protein aggregates. Here we describe a
      sensitive and simple method to follow and monitor general protein aggregation in
      human cells. Heat shock protein 27 (HSP27) is an oligomeric small heat shock
      protein that binds and keeps unfolded proteins in a folding competent state. This
      high specificity of HSP27 for aggregated proteins can be explored to monitor
      aggregation in living cells by fusing it to a fluorescent protein as Green
      Fluorescent Protein (GFP). We have constructed a HeLa stable cell line expressing
      a HSP27:GFP chimeric reporter protein and after validation, this stable cell line
      is exposed to different agents that interfere with proteostasis, namely Arsenite,
      MG132, and Abeta-peptide. Exposure to proteome destabilizers lead to re
      localization of HSP27:GFP fluorescence to foci, confirming that our reporter
      system is functional and can be used to detect and follow protein aggregation in
      living cells. This reporter is a valuable tool to setup wide-genetic screens to
      identify genes and pathways involved in protein misfolding and aggregation.

PMID- 29345425
TI  - Eligibility of sacubitril-valsartan in a real-world heart failure population: a
      community-based single-centre study.
AB  - AIMS: This study aims to investigate the eligibility of the Prospective
      Comparison of Angiotensin Receptor-Neprilysin Inhibitor (ARNI) with ACE inhibitor
      to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM
      HF) study to a real-world heart failure population. METHODS AND RESULTS: Medical
      records of all heart failure patients living within the catchment area of Umea
      University Hospital were reviewed. This district consists of around 150 000
      people. Out of 2029 patients with a diagnosis of heart failure, 1924 (95%) had at
      least one echocardiography performed, and 401 patients had an ejection fraction
      of <=35% at their latest examination. The major PARADIGM-HF criteria were
      applied, and 95 patients fulfilled all enrolment criteria and thus were eligible
      for sacubitril-valsartan. This corresponds to 5% of the overall heart failure
      population and 24% of the population with ejection fraction <= 35%. The eligible
      patients were significantly older (73.2 +/- 10.3 vs. 63.8 +/- 11.5 years), had
      higher blood pressure (128 +/- 17 vs. 122 +/- 15 mmHg), had higher heart rate (77
      +/- 17 vs. 72 +/- 12 b.p.m.), and had more atrial fibrillation (51.6% vs. 36.2%)
      than did the PARADIGM-HF population. CONCLUSIONS: Only 24% of our real-world
      heart failure and reduced ejection fraction population was eligible for
      sacubitril-valsartan, and the real-world heart failure and reduced ejection
      fraction patients were significantly older than the PARADIGM-HF population. The
      lack of data on a majority of the patients that we see in clinical practice is a
      real problem, and we are limited to extrapolation of results on a slightly
      different population. This is difficult to address, but perhaps registry-based
      randomized clinical trials will help to solve this issue.

PMID- 29345426
TI  - Single-dose intravenous iron in Southeast Asian heart failure patients: A pilot
      randomized placebo-controlled study (PRACTICE-ASIA-HF).
AB  - AIMS: Iron deficiency is highly prevalent in Southeast Asians with heart failure
      (HF) and associated with worse outcomes. This trial aimed to assess the effect of
      intravenous iron in Southeast Asians hospitalized with decompensated HF. METHODS
      AND RESULTS: Fifty patients hospitalized for acute decompensated HF, regardless
      of ejection fraction, with iron deficiency (defined as serum ferritin <300 ng/mL
      if transferrin saturation is <20%) were randomized to receive either one dose of
      intravenous ferric carboxymaltose (FCM) 1000 mg or placebo (0.9% saline)
      following HF stabilization and before discharge in two Singapore tertiary
      centres. The primary endpoint was difference in 6-min walk test (6MWT) distance
      over 12 weeks, while secondary endpoints were quality of life assessed using
      validated Kansas City Cardiomyopathy Questionnaire (KCCQ) and Visual Analogue
      Scale (VAS). Improvement in 6MWT distance at Week 12 was observed in both FCM and
      placebo groups (from 252 +/- 123 to 334 +/- 128 m and from 243 +/- 67 to 301 +/-
      83 m, respectively). Unadjusted analysis showed 6MWT distance for FCM exceeded
      that for placebo, but adjustment for baseline covariates and time attenuated this
      effect {adjusted mean difference between groups: 0.88 m [95% confidence interval
      (CI) -30.2 to 32.0, P = 0.956]}. KCCQ overall summary and VAS were similar in
      both groups [adjusted mean difference: KCCQ -1.48 (95% CI -8.27 to 5.31, P =
      0.670) and VAS 0.26 (95% CI -0.33 to 0.86, P = 0.386)]. FCM was well tolerated
      with no serious treatment-related adverse events. CONCLUSIONS: Intravenous FCM
      administered pre-discharge in Southeast Asians hospitalized with decompensated HF
      is clinically feasible. Changes in 6MWT distance should be measured beyond Week
      12 to account for background therapy effects.

PMID- 29345427
TI  - Review article: Best practice management of common shoulder injuries and
      conditions in the emergency department (part 4 of the musculoskeletal injuries
      rapid review series).
AB  - Shoulder injuries are a commonly presenting complaint to the ED. In the absence
      of an obvious deformity, they can be difficult to assess and definitively
      diagnose because of the multiple structures that cause shoulder pain, the acuity
      and severity of pain and the lack of range of motion in the ED setting. The
      quality of ED care provided to patients with musculoskeletal shoulder pain is
      crucial to ensure the best possible outcomes for the patient. This rapid review
      investigated best practice for the assessment and management of common shoulder
      injuries and conditions in the ED. Databases were searched in 2017, including
      PubMed, CINAHL, EMBASE, TRIP and the grey literature, including relevant
      organisational websites. Primary studies, systematic reviews and guidelines
      published in English-language in the past 12 years that addressed the acute
      assessment, management, follow-up plan or prognosis were considered for
      inclusion. Data extraction of included articles was conducted, followed by
      quality appraisal to rate the level of evidence. The search revealed 1902
      articles, of which 73 were included in the review (n = 12 primary articles, n =
      49 systematic reviews and n = 12 guidelines). This rapid review provides
      clinicians who manage shoulder dislocations, fractures and soft tissue injuries
      in the ED a summary of the best available evidence to enhance the quality of care
      for optimal patient outcomes. There is strong evidence to support taking a
      thorough history and physical examination, with cautious use of special tests
      because of their poor diagnostic accuracy. Key points regarding the diagnosis and
      management of these injuries are provided.

PMID- 29345428
TI  - TRAF3 regulation of inhibitory signaling pathways in B and T lymphocytes by
      kinase and phosphatase localization.
AB  - This brief review presents current understanding of how the signaling adapter
      protein TRAF3 can both induce and block inhibitory signaling pathways in B and T
      lymphocytes, via association with kinases and phosphatases, and subsequent
      regulation of their localization within the cell. In B lymphocytes, signaling
      through the interleukin 6 receptor (IL-6R) induces association of TRAF3 with IL
      6R-associated JAK1, to which TRAF3 recruits the phosphatase PTPN22 (protein
      tyrosine phosphatase number 22) to dephosphorylate JAK1 and STAT3, inhibiting IL
      6R signaling. An important biological consequence of this inhibition is
      restraining the size of the plasma cell compartment, as their differentiation is
      IL-6 dependent. Similarly, in T lymphocytes, interleukin 2 receptor (IL-2R)
      signaling recruits TRAF3, which in turn recruits the phosphatase TCPTP (T cell
      protein tyrosine phosphatase) to dephosphorylate JAK3. The resulting inhibition
      of IL-2R signaling limits the IL-2-dependent size of the T regulatory cell (Treg)
      compartment. TRAF3 also inhibits type 1 IFN receptor (IFNalphaR) signaling to T
      cells by this mechanism, restraining expression of IFN-stimulated gene
      expression. In contrast, TRAF3 association with two inhibitors of TCR signaling,
      C-terminal Src kinase (Csk) and PTPN22, promotes their localization to the
      cytoplasm, away from the membrane TCR complex. TRAF3 thus enhances TCR signaling
      and downstream T cell activation. Implications are discussed for these regulatory
      roles of TRAF3 in lymphocytes, as well as potential future directions.

PMID- 29345429
TI  - Engineering 3D Hydrogels for Personalized In Vitro Human Tissue Models.
AB  - There is a growing interest in engineering hydrogels for 3D tissue and disease
      models. The major motivation is to better mimic the physiological
      microenvironment of the disease and human condition. 3D tissue models derived
      from patients' own cells can potentially revolutionize the way treatment and
      diagnostic alternatives are developed. This requires development of tissue
      mimetic hydrogels with user defined and tunable properties. In this review
      article, a recent summary of 3D hydrogel platforms for in vitro tissue and
      disease modeling is given. Hydrogel design considerations and available hydrogel
      systems are summarized, followed by the types of currently available hydrogel
      models, such as bulk hydrogels, porous scaffolds, fibrous scaffolds, hydrogel
      microspheres, hydrogel sandwich systems, microwells, and 3D bioprinted
      constructs. Although hydrogels are utilized for a wide range of tissue models,
      this article focuses on liver and cancer models. This article also provides a
      detailed section on current challenges and future perspectives of hydrogel-based
      tissue models.

PMID- 29345430
TI  - Wearable Wireless Tyrosinase Bandage and Microneedle Sensors: Toward Melanoma
      Screening.
AB  - Wearable bendable bandage-based sensor and a minimally invasive microneedle
      biosensor are described toward rapid screening of skin melanoma. These wearable
      electrochemical sensors are capable of detecting the presence of the tyrosinase
      (TYR) enzyme cancer biomarker in the presence of its catechol substrate,
      immobilized on the transducer surface. In the presence of the surface TYR
      biomarker, the immobilized catechol is rapidly converted to benzoquinone that is
      detected amperometrically, with a current signal proportional to the TYR level.
      The flexible epidermal bandage sensor relies on printing stress-enduring inks
      which display good resiliency against mechanical deformations, whereas the hollow
      microneedle device is filled with catechol-coated carbon paste for assessing
      tissue TYR levels. The bandage sensor can thus be used directly on the skin
      whereas microneedle device can reach melanoma tissues under the skin. Both
      wearable sensors are interfaced to an ultralight flexible electronic board, which
      transmits data wirelessly to a mobile device. The analytical performance of the
      resulting bandage and microneedle sensing systems are evaluated using TYR
      containing agarose phantom gel and porcine skin. The new integrated conformal
      portable sensing platforms hold considerable promise for decentralized melanoma
      screening, and can be extended to the screening of other key biomarkers in skin
      moles.

PMID- 29345432
TI  - Getting published.

PMID- 29345431
TI  - The effect of diuresis on extravascular lung water and pulmonary function in
      acute decompensated heart failure.
AB  - AIMS: The effect of extravascular lung water (EVLW) and relationship to
      functional status as a result of acute decompensated heart failure (ADHF) are not
      well understood. We sought to quantify changes in clinical variables, EVLW,
      airway anatomy, spirometry, and diffusing capacity for carbon monoxide before and
      after treatment for ADHF. METHODS AND RESULTS: Fifteen patients were recruited
      within 24 h of hospital admission. Spirometry, diffusing capacity for carbon
      monoxide, and surrogates of EVLW by computed tomography were measured and were
      then repeated within 24 h of discharge. From the computed tomography (CT) scan,
      surrogates of EVLW were calculated from the distribution of CT attenuation of the
      lung tissue. Airways were segmented using the VIDA Apollo software. Patients were
      hospitalized for 4.6 +/- 2.1 days, had 10 +/- 4.8 L of fluid removed (7.0 +/- 4.2
      L between study visits), and lost 7.1 +/- 4.9 kg. Patients had significant
      clearance of fluid from the lungs (per cent change: mean, 4.2 +/- 6.1%; skew,
      17.5 +/- 27.0%; kurtosis, 37.6 +/- 56.7%; full-width half-maximum, 10.2 +/-
      13.5%). Static lung volumes and maximal flows improved significantly (per cent
      change: forced vital capacity, 14.5 +/- 13.6%; forced expiratory volume in 1 s,
      15.9 +/- 14.0%; forced expiratory flow at 25-75% of forced vital capacity, 27.2
      +/- 42.9%). The ratio of membrane conductance to capillary blood volume improved
      significantly (per cent change: alveolar-capillary membrane conductance/capillary
      blood volume, 23.4 +/- 22.8%). Weight loss during hospitalization was
      significantly correlated with improved spirometry and diffusing capacity.
      CONCLUSIONS: Extravascular lung water contributes to the pulmonary congestive
      syndrome in ADHF patients, and its clearance is an important component of the
      improvement in pulmonary function as a result of inpatient treatment.

PMID- 29345433
TI  - Phenotype and Function of Somatic Primary Afferent Nociceptive Neurones with C-,
      Adelta- or Aalpha/beta-Fibres.
AB  - Nociceptive dorsal root ganglion (DRG) neurones have fibres that conduct in the
      C, Adelta and Aalpha/beta conduction velocity range. The properties of
      nociceptive compared with non-nociceptive somatic afferent dorsal root ganglion
      neurones appear to fall into two patterns, A and B. Pattern A properties of
      nociceptive neurones, the more common type, include longer action potential
      duration and slower maximum rate of fibre firing, as well as a greater expression
      of substance P and calcitonin gene-related peptide immunoreactivity. The values
      of pattern A properties appear to be graded according to the conduction velocity
      group (C, Adelta or Aalpha/beta) of the fibres. The most pronounced forms of A
      type properties are expressed by nociceptive neurones with C-fibres, and these
      become less pronounced in nociceptive neurones with Adelta-fibres and least
      pronounced in those with Aalpha/beta fibres (C > Adelta > Aalpha/beta). Some of
      these properties are also expressed in a less extreme but similarly graded manner
      through C, Adelta and Aalpha/beta groups of non-nociceptive low threshold
      mechanoreceptive (LTM) neurone. The less common pattern B properties of
      nociceptive neurones have similar values in C-, Adelta- and Aalpha/beta-fibre
      nociceptive neurones but these clearly differ from LTM units with C-, Adelta- and
      Aalpha/beta-fibre conduction velocities. These features of nociceptive neurones
      include consistently larger action potential overshoots and longer after
      hyperpolarisation durations in nociceptive than in LTM neurones.

PMID- 29345434
TI  - Two-Photon-Excited Silica and Organosilica Nanoparticles for Spatiotemporal
      Cancer Treatment.
AB  - Coherent two-photon-excited (TPE) therapy in the near-infrared (NIR) provides
      safer cancer treatments than current therapies lacking spatial and temporal
      selectivities because it is characterized by a 3D spatial resolution of 1 um3 and
      very low scattering. In this review, the principle of TPE and its significance in
      combination with organosilica nanoparticles (NPs) are introduced and then studies
      involving the design of pioneering TPE-NIR organosilica nanomaterials are
      discussed for bioimaging, drug delivery, and photodynamic therapy. Organosilica
      nanoparticles and their rich and well-established chemistry, tunable composition,
      porosity, size, and morphology provide ideal platforms for minimal side-effect
      therapies via TPE-NIR. Mesoporous silica and organosilica nanoparticles endowed
      with high surface areas can be functionalized to carry hydrophobic and
      biologically unstable two-photon absorbers for drug delivery and diagnosis.
      Currently, most light-actuated clinical therapeutic applications with NPs involve
      photodynamic therapy by singlet oxygen generation, but low photosensitizing
      efficiencies, tumor resistance, and lack of spatial resolution limit their
      applicability. On the contrary, higher photosensitizing yields, versatile
      therapies, and a unique spatial resolution are available with engineered two
      photon-sensitive organosilica particles that selectively impact tumors while
      healthy tissues remain untouched. Patients suffering pathologies such as
      retinoblastoma, breast, and skin cancers will greatly benefit from TPE-NIR
      ultrasensitive diagnosis and therapy.

PMID- 29345435
TI  - N-Modified NiO Surface for Superior Alkaline Hydrogen Evolution.
AB  - Boosting the sluggish kinetics of the hydrogen evolution reaction in alkaline
      environments is key for the large-scale application of water-alkali and chlor
      alkali electrolysis. In this study, nitrogen atoms are used to precisely modulate
      electrochemical active sites on the surface of nickel oxide with low-coordinated
      oxygen atoms, to achieve enhanced kinetics in alkaline hydrogen evolution.
      Theoretical and experimental results demonstrate that surface charge
      redistribution after modulation facilitates both the initial water dissociation
      step and the subsequent recombination of Had from low-coordinated oxygen sites
      and desorption of OHad- from nickel sites, thus accelerating the overall hydrogen
      evolution process. The N-modulated nickel oxide enriched in low-coordinated
      oxygen atoms exhibits significantly enhanced activity with a small overpotential
      of -100 mV at the current density of -10 mA cm-2 and a robust stability over 90 h
      for hydrogen evolution in 1.0 m KOH.

PMID- 29345436
TI  - Effect of ginseng therapy on diabetes and its chronic complications: lessons
      learned.
AB  - Ginseng played a significant role in the management of diabetes in China and in
      other Asian countries for a long period of time. It has a large number of
      pharmacological properties and is relatively free from adverse effects. As a part
      of Ontario Ginseng Research and Innovation Consortium, we investigated the
      effects of ginseng extract on diabetes and its complications. We demonstrated
      large number of beneficial effects of ginseng therapy and showed that these
      effects are possibly mediated through its antioxidant properties. Thus ginseng
      may lend itself as a relatively safe and inexpensive adjuvant treatment for
      diabetes and chronic diabetic complications.

PMID- 29345437
TI  - Antioxidant and acetylcholinesterase inhibitory activities of ginger root
      (Zingiber officinale Roscoe) extract.
AB  - Background Zingiber officinale Roscoe has been used in traditional medicine for
      the treatment of neurological disorder. This study aimed to investigate the
      phenolic contents, antioxidant, acetylcholinesterase enzyme (AChE) inhibitory
      activities of different fraction of Z. officinale root grown in Vietnam. Methods
      The roots of Z. officinale are extracted with ethanol 96 % and fractionated with
      n-hexane, ethyl acetate (EtOAc) and butanol (BuOH) solvents. These fractions
      evaluated the antioxidant activity by 1,1-Diphenyl -2-picrylhydrazyl (DPPH) assay
      and AChE inhibitory activity by Ellman's colorimetric method. Results Our data
      showed that the total phenolic content of EtOAc fraction was highest equivalents
      to 35.2+/-1.4 mg quercetin/g of fraction. Our data also demonstrated that EtOAc
      fraction had the strongest antioxidant activity with IC50 was 8.89+/-1.37 ug/mL
      and AChE inhibitory activity with an IC50 value of 22.85+/-2.37 MUg/mL in a dose
      dependent manner, followed by BuOH fraction and the n-hexane fraction is the
      weakest. Detailed kinetic analysis indicated that EtOAc fraction was mixed
      inhibition type with Ki (representing the affinity of the enzyme and inhibitor)
      was 30.61+/-1.43 ug/mL. Conclusions Our results suggest that the EtOAc fraction
      of Z. officinale may be a promising source of AChE inhibitors for Alzheimer's
      disease.

PMID- 29345438
TI  - Evaluation of hepatic glycogen content, some haematological and biochemical
      parameters of alloxan-induced diabetic rats treated with combinations of
      glibenclamide and G. latifolium extract.
AB  - Background Diabetes is associated with both biochemical and haematological
      complications. Combination therapy has been advocated to mitigate some of these
      complications. Aim This study was designed to investigate the effects of
      glibenclamide and Gongronema latifolium (GL) on hepatic glycogen content and
      haemato-biochemical parameters. Methods Thirty male Wistar rats were assigned
      into five groups of six rats each. Groups 2-5 rats received intraperitoneally,
      160 mg/kg of alloxan monohydrate while group 1 rats served as normal control.
      Groups 2-5 rats were respectively treated with 10 mL/kg distilled water (DW), 2
      mg/kg glibenclamide, 200 mg/kg GL and 2 mg/kg glibenclamide and 200 mg/kg GL,
      while group 1 rats received 10 mL/kg DW. All treatments were per os daily for 21
      days. Blood samples for investigation of haemato-biochemical (red blood cell
      [RBC], packed cell volume [PCV], haemoglobin concentration [Hb], blood urea
      nitrogen [BUN] and creatinine) parameters were collected on days 7, 14 and 21
      post-treatment (PT), while the liver sample for hepatic glycogen determination
      was obtained on day 21 PT. Results Creatinine and BUN values of groups 3 and 4
      rats were comparable to that of group 1 but were significantly (p<0.05) lower
      when compared with those of groups 2 and 5. There were significant (p<0.05)
      increases in the mean hepatic glycogen content, RBC, PCV, and Hb of group 4 rats
      when compared to those of group 2. Conclusions It was concluded that a
      combination of glibenclamide and G. latifolium in treatment of diabetic rats
      improved glycogen storage and demonstrated beneficial effects on haematology and
      kidney marker parameters.

PMID- 29345439
TI  - Bivalirudin versus Heparin Monotherapy in Myocardial Infarction.

PMID- 29345440
TI  - Bivalirudin versus Heparin Monotherapy in Myocardial Infarction.

PMID- 29345441
TI  - Bivalirudin versus Heparin Monotherapy in Myocardial Infarction.

PMID- 29345442
TI  - Lung uptake of fluorine-18 fluoroethyl-choline PET-CT in patients with prostate
      cancer.
AB  - BACKGROUND: Metastatic spreading to the lungs is a negative prognostic factor in
      patients with prostate cancer (PC). Aim of our study was to assess the prevalence
      of lung PC metastases in patients with fluorine-18 fluoroethyl-choline (F-18
      FECh) PET-CT positive lung lesions and the role of Gleason Score (GS) and common
      biochemical markers in predicting metastatic spreading to the lungs. METHODS: We
      retrospectively evaluated the scans of 1283 patients ongoing (F-18-FECh) PET-CT
      for PC between May 2010 and July 2014. Patients with lung lesion with F-18-FECh
      uptake were included. Data concerning GS at diagnosis, "trigger" prostate
      specific antigen (PSAtr), PSA doubling time (PSAdt), PSA velocity (PSAvel) and
      ongoing androgen deprivation therapy were collected. PET-CT findings were
      confirmed by histology or followup (FU) and classified as follows: inflammation,
      primary lung cancer or metastases from tumour other than PC, and lung metastases
      from PC. RESULTS: Twenty-two patients with F-18-FECh positive lung lesion and
      available histology or FU were identified. PSAdt was significantly (p=0.029)
      shorter in patients with lung metastases from PC (median PSAdt 1.7 months,
      interquartile range [IQR] 1.5-4.1 months) than in patients without lung PC
      relapse (median PSAdt 6.7 months, IQR 3.9-7.8); PSAvel was significantly
      (p=0.019) higher in patients with lung metastases from PC (median PSAvel 3.2
      ng/ml/month, IQR 0.65-6.65 ng/ml/month) than in patients without lung PCrelapse
      (median PSAvel 0.3 ng/ml/month, IQR 0.2-0.5 ng/ml/month). Patients with lung
      metastases from PC had significantly (p=0.006) higher GS at diagnosis (median GS
      8) than the other ones (median GS 7). CONCLUSIONS: Our analysis shows that the
      prevalence of F-18-FECh positive lung metastases in patients with PC, especially
      with higher GS at diagnosis, is higher in presence of a steady increase in PSA
      values, confirmed by higher PSAvel and shorter PSAdt.

PMID- 29345443
TI  - SUV calculation in breast cancer: which normalization should be applied when
      using 18F-FDG PET?
AB  - BACKGROUND: When using 18F-FDG PET, glucose metabolism quantification is affected
      by various factors. We aimed to investigate the benefit of different SUV
      normalizations to improve the accuracy of 18F-FDG uptake to predict breast cancer
      aggressiveness and response to treatment. METHODS: Two hundred fifty-two women
      with locally advanced breast cancer treated with neoadjuvant chemotherapy (NAC)
      were included. Women underwent 18F-FDG PET before and after the first course of
      NAC. Glucose serum levels, patient heights and weights were recorded at the time
      of each PET exam. Four different procedures for SUV normalization of the primary
      tumor were used: by body weight (SUVBW by blood glucose level ( SUVG, by lean
      body mass (SUL) and then corrected for both lean body mass and blood glucose
      level ( SULG). RESULTS: At baseline, SUL was significantly lower than SUVBW
      (5.9+/-4.0 and 9.5+/-6.5, respectively; p<1.10-4), whereas SUVG and SUVBW were
      not significantly different (9.7+/-6.4 and 9.5+/-6.5, respectively; P=0.67).
      Concerning SUV changes (DeltaSUV), the different normalizations methods did not
      induce significant quantitative differences. The correlation coefficients were
      high between the four normalizations methods of SUV1, SUV2 and DeltaSUVB (R>0.95;
      p<1.10-4). High baseline SUVBW measures were positively correlated with the
      biological tumor characteristics of aggressiveness and proliferation (p<1.10-3):
      ductal carcinoma, high tumor grading, high mitotic activity, negative estrogen
      receptor status and the TNBC subtype. DeltaSUVBW was highly predictive of pCR
      (AUC=0.76 on ROC curve analysis; p<1.10-4). The different SUV normalizations
      yields identical statistical results and AUC to predict tumor biological
      aggressiveness and response to therapy. CONCLUSIONS: In the present setting,
      SUVBW and SUL can be considered as robust measures and be used in future
      multicentre trials. The additional normalization of SUV by glycemia involves
      stringent methodologic procedures to avoid biased risk measurements and offers no
      statistical advantages.

PMID- 29345444
TI  - Bivalirudin versus Heparin Monotherapy in Myocardial Infarction.

PMID- 29345445
TI  - The impact of high progesterone levels on the day of HCG administration in
      assisted human reproduction treatments.
AB  - OBJECTIVE: Progesterone is a steroid hormone that acts on the endometrium. It is
      known for producing physical and mood-related side effects. Few studies have
      looked into how progesterone levels affect embryo development and quality. This
      study aimed to find a cutoff level for serum progesterone on the day of HCG
      administration from which embryo quality is impaired. METHODS: The study included
      145 cycles, from which 885 oocytes and 613 embryos were obtained. All patients
      had their serum progesterone levels measured on the day of HCG administration.
      Data sets were collected from patient medical records. The chi-square test was
      used to assess qualitative variables and the Mann-Whitney test to evaluate
      quantitative variables. RESULTS: Statistical analysis revealed that serum
      progesterone levels and reproductive variables were not significantly associated.
      In regards to oocyte maturity, however, when progesterone levels were greater
      than 1.3 ng/mL the probability of oocytes being immature increased by 12.7%. The
      fragmentation rate of embryos categorized as "top quality" in D3 increased
      proportionately to increases in progesterone levels (12.23%). CONCLUSION: High
      progesterone levels appeared to be correlated with increased embryo fragmentation
      rates, but high serum levels of the hormone on the day of HCG administration had
      no impact on reproductive variables and were not associated with impaired embryo
      development.

PMID- 29345446
TI  - The first South American case of pre-implantation genetic diagnosis to select
      compatible embryo for cord blood transplantation as treatment for sickle cell
      anemia.
AB  - Sickle cell anemia is an inherited systemic hemoglobinopathy that affects
      hemoglobin production in red blood cells, leading to early morbidity and
      mortality. It is caused by a homozygous nucleotide substitution (c.20A>T) in the
      beta-globin gene (HBB) that changes a glutamic acid to a valine in the protein.
      We present a case report of a fertile couple, both carriers of the sickle cell
      anemia mutation, with one affected daughter. Six cycles of assisted reproductive
      techniques were performed, resulting in 53 embryos in cleavage stage. Each embryo
      was biopsied and analyzed for pre-implantation genetic diagnosis (PGD) by
      fluorescent polymerase chain reaction, using polymorphic markers of the region of
      interest followed by capillary electrophoresis in an automated genetic analyzer.
      HLA Compatible and normal embryos for the mutation represented 3 (5.66%); while
      the carriers and compatible 6 (11.32%); therefore, embryos matching those of the
      affected daughter represented 9 (16.98%). A selected embryo in blastocyst stage
      was transferred, resulting in a healthy male newborn, who had the umbilical cord
      blood cells collected and stored. The affected daughter was immunosuppressed and
      received transplanted cells from the umbilical cord blood of her brother; the
      treatment was successful. Embryo selection using PGD technologies represent the
      most effective treatment plan for parents who want to have a healthy child, and
      it could cure another child already affected by inherited hemoglobinopathy.

PMID- 29345447
TI  - Evaluation and Management of Lower-Extremity Ulcers.

PMID- 29345448
TI  - Evaluation and Management of Lower-Extremity Ulcers.

PMID- 29345449
TI  - Evaluation and Management of Lower-Extremity Ulcers.

PMID- 29345450
TI  - Noninferiority Trials.

PMID- 29345451
TI  - Gadolinium-Loaded Solid Lipid Nanoparticles as a Tumor-Absorbable Contrast Agent
      for Early Diagnosis of Colorectal Tumors Using Magnetic Resonance Colonography.
AB  - Magnetic resonance (MR) contrast agents focusing on special functions are
      required to improve cancer diagnosis, particularly in the early stages. Here, we
      designed multifunctional solid lipid nanoparticles (SLNs) with simultaneous
      loading of gadolinium (Gd) diethylenetriaminepentaacetic acid (Gd-DTPA) and
      octadecylamine fluorescein isothiocyanate (FITC) to obtain Gd-FITC-SLNs as a
      tumor-absorbable nanoparticle contrast agent for the histological confirmation of
      MR imaging (MRI) findings. Colorectal tumors were evaluated in vitro and in vivo
      via direct uptake of this contrast agent, which displayed reasonable T1
      relaxivity and no significant cytotoxicity at the experimental concentrations in
      human colon carcinoma cells (HT29) and mouse colon carcinoma cells (CT26). In
      vitro cell uptake experiments demonstrated that contrast agent absorption by the
      two types of cancer cells was concentration-dependent in the safe concentration
      range. During in vivo MRI, transrectal infusion of Gd-FITC-SLNs showed more
      significant enhancement at the tumor site compared with the infusion of Gd-DTPA
      in female C57/BL mice with azoxymethane/dextran sulfate sodium-induced colorectal
      highgrade intraepithelial neoplasia. Subsequent confocal fluorescence microscopy
      demonstrated Gd-FITC-SLNs as highly concentrated green fluorescent spots
      distributed from the tumor capsule into the tumor. This study establishes the
      "proof-of-principle" of a new MRI technique wherein colorectal tumors are
      enhanced via direct absorption or uptake of the nanoparticle contrast agent.

PMID- 29345452
TI  - Noninferiority Trials.

PMID- 29345453
TI  - Poly(glycidol) Coating on Ultrahigh Molecular Weight Polyethylene for Reduced
      Biofilm Growth.
AB  - Semibranched poly(glycidol) (PG-OH) and poly(glycidol allylglycidyl ether) (PG
      Allyl) coatings were formed on ultrahigh molecular weight polyethylene (UMWPE) in
      a unique two-step process which included radiation of UHMWPE followed by grafting
      of PG-OH or PG-Allyl to the surface via free radical cross-linking. Resulting
      surfaces were extensively characterized by FTIR-ATR, XPS, fluorescent microscopy,
      and contact goniometry. The performance was evaluated using the most prominent
      biofilm-forming bacteria Staphylococcus aureus for 24 and 48 h. The PG-Allyl
      coating demonstrated a 3 log reduction in biofilm growth compared to noncoated
      control, demonstrating a promising potential to inhibit adherence and
      colonization of biofilm-forming bacteria that often develop into persistent
      infections.

PMID- 29345454
TI  - Stability and Performance of CsPbI2Br Thin Films and Solar Cell Devices.
AB  - In this manuscript, the inorganic perovskite CsPbI2Br is investigated as a
      photovoltaic material that offers higher stability than the organic-inorganic
      hybrid perovskite materials. It is demonstrated that CsPbI2Br does not
      irreversibly degrade to its component salts as in the case of methylammonium lead
      iodide but instead is induced (by water vapor) to transform from its metastable
      brown cubic (1.92 eV band gap) phase to a yellow phase having a higher band gap
      (2.85 eV). This is easily reversed by heating to 350  degrees C in a dry
      environment. Similarly, exposure of unencapsulated photovoltaic devices to water
      vapor causes current (JSC) loss as the absorber transforms to its more
      transparent (yellow) form, but this is also reversible by moderate heating, with
      over 100% recovery of the original device performance. NMR and thermal analysis
      show that the high band gap yellow phase does not contain detectable levels of
      water, implying that water induces the transformation but is not incorporated as
      a major component. Performances of devices with best efficiencies of 9.08% (VOC =
      1.05 V, JSC = 12.7 mA cm-2 and FF = 68.4%) using a device structure comprising
      glass/ITO/c-TiO2/CsPbI2Br/Spiro-OMeTAD/Au are presented, and further results
      demonstrating the dependence of the performance on the preparation temperature of
      the solution processed CsPbI2Br films are shown. We conclude that encapsulation
      of CsPbI2Br to exclude water vapor should be sufficient to stabilize the cubic
      brown phase, making the material of interest for use in practical PV devices.

PMID- 29345455
TI  - Three-Dimensional Printing of Bisphenol A-Free Polycarbonates.
AB  - Polycarbonates are widely used in food packages, drink bottles, and various
      healthcare products such as dental sealants and tooth coatings. However,
      bisphenol A (BPA) and phosgene used in the production of commercial
      polycarbonates pose major concerns to public health safety. Here, we report a
      green pathway to prepare BPA-free polycarbonates (BFPs) by thermal ring-opening
      polymerization and photopolymerization. Polycarbonates prepared from two cyclic
      carbonates in different mole ratios demonstrated tunable mechanical stiffness,
      excellent thermal stability, and high optical transparency. Three-dimensional
      (3D) printing of the new BFPs was demonstrated using a two-photon laser direct
      writing system and a rapid 3D optical projection printer to produce structures
      possessing complex high-resolution geometries. Seeded C3H10T1/2 cells also showed
      over 95% viability with potential applications in biological studies. By
      combining biocompatible BFPs with 3D printing, novel safe and high-performance
      biomedical devices and healthcare products could be developed with broad long
      term benefits to society.

PMID- 29345456
TI  - Preoccupation of Empty Carriers Decreases Endo-/Lysosome Escape and Reduces the
      Protein Delivery Efficiency of Mesoporous Silica Nanoparticles.
AB  - Endo-/lysosome escape is a major challenge in nanoparticle-based protein delivery
      for cancer therapy. To enhance the endo-/lysosomal escape and increase the
      efficacy of protein delivery, current strategies mainly focus on destroying endo
      /lysosomes by employing modified nanoparticles, such as pH-sensitive polyplexes,
      cell-penetrating peptides, and photosensitive molecules. Herein, we hypothesize
      that pretreatment with empty nanocarriers might make endo-/lysosomes occupied and
      affect the endo/lysosomal escape of protein subsequently delivery by
      nanocarriers. We first treated breast carcinoma MDA-MB-231 cells with a high
      concentration of empty nanocarriers, mesoporous silica nanoparticles (MSN), to
      occupy the endo-/lysosome. After 2 h, we treated the cells with a lower
      concentration of fluorescein isothiocyanate-labeled MSN (MSN-FITC) and
      investigated the intracellular spatial and temporal distribution of MSN-FITC and
      their colocalization with endo-/lysosomes. We discovered the preoccupation of
      endo-/lysosomes by the empty nanocarriers did exist, mainly through changing the
      spatial distribution of the subsequently introduced nanocarriers. Furthermore,
      for the protein delivery, we observed reduced MSN-saporin delivery after endo
      /lysosome preoccupation by MSN empty carriers. A similar result is observed for
      the delivery of cytochrome C by MSN but not for the small-molecule anticancer
      drug doxorubicin. The results show that the empty nanocarriers inhibit the endo
      /lysosome intracellular trafficking process and decrease the endo-/lysosome
      escape of proteins subsequently delivered by the nanocarriers. This new
      discovered phenomenon of declined endo-/lysosome escape after endo-/lysosome
      preoccupation indicates that repeated treatment by nanomaterials with low protein
      loading capacity may not yield a good cancer therapeutic effect. Therefore, it
      provides a new insightful perspective on the role of nanomaterial carriers in
      intracellular protein delivery.

PMID- 29345457
TI  - Lithium Expulsion from the Solid-State Electrolyte Li6.4La3Zr1.4Ta0.6O12 by
      Controlled Electron Injection in a SEM.
AB  - The garnet ionic conductor is one of the promising candidate electrolytes for all
      solid-state secondary lithium batteries, thanks to its high lithium ion
      conductivity and good thermal and chemical stability. However, its microstructure
      is difficult to approach because it is very sensitive to the inquisitive electron
      beam. In this study based on a scanning electron microscope (SEM), we found that
      the electron beam expulses the lithium out of Li6.4La3Zr1.4Ta0.6O12 (LLZTO), and
      the expulsed zone expands to where a stationary beam could extend and penetrate.
      The expulsion of metallic lithium was confirmed by its oxidation reaction after
      nitrogen inflow into the SEM. This phenomenon may provide us an effective probe
      to peer into the conductive nature of this electrolyte. A frame-scan scheme is
      employed to measure the expulsion rate by controllable and more uniform incidence
      of electrons. Lithium accumulation processes are continuously recorded and
      classified into four modes by fitting its growth behaviors into a dynamic
      equation that is mainly related to the initial ion concentration and ion
      migration rate in the electrolyte. These results open a novel possibility of
      using the SEM probe to gain dynamic information on ion migration and lithium
      metal growth in solid materials.

PMID- 29345458
TI  - Synthesis of Magnetite-Semiconductor-Metal Trimer Nanoparticles through
      Functional Modular Assembly: A Magnetically Separable Photocatalyst with
      Photothermic Enhancement for Water Reduction.
AB  - Hybrid nanoparticles have intrinsic advantages to achieve better activity in
      photocatalysis compared to single-component materials, as it can synergistically
      combine functional components, which promote light absorption, charge
      transportation, surface reaction, and catalyst regeneration. Through functional
      modular assembly, a rational and stepwise approach has been developed to
      construct Fe3O4-CdS-Au trimer nanoparticles and its derivatives as magnetically
      separable catalysts for photothermo-catalytic hydrogen evolution from water. In a
      typical step-by-step synthetic process, Fe3O4-Ag dimers, Fe3O4-Ag2S dimers, Fe3O4
      CdS dimers, and Fe3O4-CdS-Au trimers were synthesized by seeding growth,
      sulfuration, ion exchange, and in situ reduction consequently. Following the same
      reaction route, a series of derivative trimer nanoparticles with alternative
      semiconductor and metal were obtained for water-reduction reaction. The
      experimental results show that the semiconductor acts as an active component for
      photocatalysis, the metal nanoparticle acts as a cocatalyst for enhancement of
      charge separation, and the Fe3O4 component helps in the convenient separation of
      catalysts in magnetic field and improves photocatalytic activity under near
      infrared illumination due to photothermic effect.

PMID- 29345459
TI  - Bifunctional Hybrid Catalysts with Perovskite LaCo0.8Fe0.2O3 Nanowires and
      Reduced Graphene Oxide Sheets for an Efficient Li-O2 Battery Cathode.
AB  - In this paper, bifunctional catalysts consisting of perovskite LaCo0.8Fe0.2O3
      nanowires (LCFO NWs) with reduced graphene oxide (rGO) sheets were prepared for
      use in lithium-oxygen (Li-O2) battery cathodes. The prepared LCFO@rGO composite
      was explored as a cathode catalyst for Li-O2 batteries, resulting in an
      outstanding discharge capacity (ca. 7088.2 mAh g-1) at the first cycle. Moreover,
      a high stability of the O2-cathode with the LCFO@rGO catalyst was achieved over
      56 cycles under the capacity limit of 500 mAh g-1 with a rate of 200 mA g-1, as
      compared to the Ketjenblack carbon and LCFO NWs. The enhanced electrochemical
      performance suggests that these hybrid composites of perovskite LCFO NWs with rGO
      nanosheets could be a perspective bifunctional catalyst for the cathode oxygen
      reduction and oxygen evolution reactions in the development of next-generation Li
      O2 battery cathodes.

PMID- 29345460
TI  - Low-Cost Room-Temperature Synthesis of NaV3O8.1.69H2O Nanobelts for Mg Batteries.
AB  - Potentially safe and economically feasible magnesium batteries (MBs) have
      attracted tremendous research attention as an alternative to high-cost and unsafe
      lithium ion batteries. In the current work, for the first time, we report a novel
      room-temperature approach to dope the atomic species sodium between the vanadium
      oxide crystal lattice to obtain NaV3O8.1.69H2O (NVO) nanobelts. The synthesized
      NVO nanobelts are used as electrode materials for MBs. The MB cells demonstrate
      stable discharge specific capacity of 110 mA h g-1 at a current density of 10 mA
      g-1 and a high cyclic stability, that is 80% capacity retention after 100 cycles,
      at a current density of 50 mA g-1. Moreover, the effects of cutoff voltages
      (ranging from 2 to 2.6 V) on their electrochemical performance were investigated.
      The reason for the limited specific capacity of MBs is attributed to the trapping
      of Mg ions inside the NVO lattices. This work opens up a new pathway to explore
      different electrode materials for MBs with improved electrochemical performance.

PMID- 29345461
TI  - Combined Iron/Hydroxytriazole Dual Catalytic System for Site Selective Oxidation
      Adjacent to Azaheterocycles.
AB  - This report details a new method for site-selective methylene oxidation adjacent
      to azaheterocycles. A dual catalysis approach, utilizing both an iron Lewis acid
      and an organic hydroxylamine catalyst, proved highly effective. We demonstrate
      that this method provides complementary selectivity to other known catalytic
      approaches and represents an improvement over current heterocycle-selective
      reactions that rely on stoichiometric activation.

PMID- 29345462
TI  - Fluorescent Zn-PDC/Tb3+ Coordination Polymer Nanostructure: A Candidate for
      Highly Selective Detections of Cefixime Antibiotic and Acetone in Aqueous System.
AB  - Tb3+-doped zinc-based coordination polymer nanospindle bundles (Zn-PDC/Tb3+, or
      [Zn(2,5-PDC)(H2O)2].H2O/Tb3+) were synthesized by a simple solution precipitation
      route at room temperature, employing Zn(NO3)2, Tb(NO3)3, and 2,5-Na2PDC as the
      initial reactants, and a mixture of water and ethanol with the volume ratio of
      10:10 as the solvent. The as-obtained nanostructures presented strong fluorescent
      emission under the excitation of 298 nm light, which was attributed to the
      characteristic emission of the Tb3+ ion. It was found that the above-mentioned
      strong fluorescence of the nanostructures could be selectively quenched by
      cefixime (CFX) in aqueous solution. The other common antibiotics hardly
      interfered. Thus, as-obtained Zn-PDC/Tb3+ nanostructures could be prepared as a
      highly sensitive fluorescence probe for selective detection of CFX in an aqueous
      system. The corresponding detection limit reached 72 ppb. The theoretic
      calculation and UV-vis absorption experiments confirmed that the fluorescence
      quenching of Zn-PDC/Tb3+ nanostructures toward CFX should be attributed to the
      electron transfer and the fluorescence inner filter effect between the
      fluorescent matter and the analyte. In addition, the strong fluorescence of the
      nanostructures could also be selectively quenched by acetone in the water system.

PMID- 29345463
TI  - (+/-)-Sativamides A and B, Two Pairs of Racemic Nor-Lignanamide Enantiomers from
      the Fruits of Cannabis sativa.
AB  - (+/-)-Sativamides A (1) and B (2), two pairs of nor-lignanamide enantiomers
      featuring a unique benzo-angular triquinane skeleton, were isolated from the
      fruits of Cannabis sativa (hemp seed). Their structures were elucidated by
      detailed spectroscopic analysis and ECD calculations. The resolution of (+)- and
      (-)-sativamides A and B were achieved by chiral HPLC. Pretreatment of
      neuroblastoma cells with 1 and 2 significantly reduced the endoplasmic reticulum
      (ER) stress-induced cytotoxicity.

PMID- 29345464
TI  - Whole Egg Consumption Exerts a Nephroprotective Effect in an Acute Rodent Model
      of Type 1 Diabetes.
AB  - Nephropathy is a well-characterized complication of type 1 diabetes (T1D),
      resulting in proteinuria and urinary loss of micronutrients. We previously found
      that a whole egg-based diet maintained vitamin D balance in type 2 diabetic rats
      despite excessive urinary losses due to nephropathy. The goal of this study was
      to investigate the impact of whole egg consumption in T1D rats. Sprague-Dawley
      rats were randomly assigned to T1D or nondiabetic control groups and fed a casein
      or whole egg-based diet for 32 days. On day 26, two-thirds of the rats received a
      streptozotocin injection to induce T1D. Whole egg consumption attenuated
      polyuria, proteinuria, and renal hypertrophy in T1D rats. These data suggest that
      dietary intervention with whole egg may offer renal protection in T1D.

PMID- 29345465
TI  - Microplastic Abundance and Composition in Western Lake Superior As Determined via
      Microscopy, Pyr-GC/MS, and FTIR.
AB  - While plastic pollution in marine and freshwater systems is an active area of
      research, there is not yet an in-depth understanding of the distributions,
      chemical compositions, and fates of plastics in aquatic environments. In this
      study, the magnitude, distribution, and common polymers of microplastic pollution
      in surface waters in western Lake Superior are determined. Analytical
      methodology, including estimates of ambient contamination during sample
      collection and processing, are described and employed. Microscopy, pyrolysis-gas
      chromatography/mass spectrometry (Pyr-GC/MS), and Fourier transform infrared
      spectroscopy (FTIR) were used to quantify and identify microplastic particles. In
      surface waters, fibers were the most frequently observed morphology, and, based
      upon PyGC/MS analysis,  polyvinyl chloride was the most frequently observed
      polymer, followed by polypropylene and polyethylene. The most common polymer
      identified by FTIR was polyethylene. Despite the low human population in Lake
      Superior's watershed, microplastic particles (particularly fibers, fragments, and
      films) were identified in western-lake surface waters at levels comparable to
      average values reported in studies within Lake Michigan, the North Atlantic
      Ocean, and the South Pacific Ocean. This study provides insight into the
      magnitude of microplastic pollution in western Lake Superior, and describes in
      detail methodology to improve future microplastics studies in aquatic systems.

PMID- 29345466
TI  - Flow Photochemistry as a Tool for the Total Synthesis of (+)-Epigalcatin.
AB  - The first total synthesis of (+)-epigalcatin was completed in a highly
      stereoselective manner starting from piperonal, 3,4-dimethylbenzaldehyde, and
      diethyl succinate. l-Prolinol was used as a chiral auxiliary. The crucial step in
      this procedure involves the construction of the cyclolignan framework by
      continuous-flow photocyclization of a chiral atropisomeric 1,2
      bisbenzylidenesuccinate amide ester.

PMID- 29345468
TI  - Photochemistry of Solid Films of the Neonicotinoid Nitenpyram.
AB  - The environmental fates of nitenpyram (NPM), a widely used neonicotinoid
      insecticide, are not well-known. A thin solid film of NPM deposited on a
      germanium attenuated total reflectance (ATR) crystal was exposed to radiation
      from a low-pressure mercury lamp at 254 nm, or from broadband low pressure
      mercury photolysis lamps centered at 350 or 313 nm. The loss during photolysis
      was followed in time using FTIR. The photolysis quantum yields (phi), defined as
      the number of NPM molecules lost per photon absorbed, were determined to be (9.4
      +/- 1.5) * 10-4 at 350 nm, (1.0 +/- 0.3) * 10-3 at 313 nm, and (1.2 +/- 0.4) * 10
      2 at 254 nm (+/-2sigma). Imines, one with a carbonyl group, were detected as
      surface-bound products and gaseous N2O was generated in low (11%) yield. The UV
      vis absorption spectra of NPM in water was different from that in acetonitrile,
      dichloromethane, and methanol, or in a thin solid film. The photolytic lifetime
      of solid NPM at a solar zenith angle at 35 degrees  is calculated to be 36 min,
      while that for NPM in water is 269 min, assuming that the quantum yield is the
      same as in the solid. Thus, there may be a significant sensitivity to the medium
      for photolytic degradation and the lifetime of NPM in the environment.

PMID- 29345467
TI  - Cyclic Acyl Disulfides and Acyl Selenylsulfides as the Precursors for Persulfides
      (RSSH), Selenylsulfides (RSeSH), and Hydrogen Sulfide (H2S).
AB  - The reactions of three model compounds (1-3) for cyclic acyl disulfides and
      cyclic acyl selenylsulfides are studied. These compounds were found to be
      effective precursors for persulfides (RSSH) and selenylsulfides (RSeSH) upon
      reacting with nucleophilic species. They could also act as H2S donors when
      interacting with cellular thiols. The most interesting discovery was the
      generation of RSeSH from compound 3 under mild conditions. Selenylsulfides
      (RSeSH) are expected to be important regulating molecules involved in Sec-related
      redox signaling. The method of producing RSeSH should allow researchers to better
      understand the chemical biology of RSeSH.

PMID- 29345469
TI  - A Large Family of Centrosymmetric and Chiral f-Element-Bearing Iodate Selenates
      Exhibiting Coordination Number and Dimensional Reductions.
AB  - The exploration of phase formation in the f-element-bearing iodate selenate
      system has resulted in 14 novel rare-earth-containing iodate selenates,
      Ln(IO3)(SeO4) (Ln = La, Ce, Pr, Nd; LnISeO-1), Ln(IO3)(SeO4)(H2O) (Ln = Sm, Eu;
      LnISeO-2), and Ln(IO3)(SeO4)(H2O)2.H2O (Ln = Gd, Dy, Ho, Er, Tm, Yb, Lu, Y;
      LnISeO-3), as well as two new thorium iodate selenates, Th(OH)(IO3)(SeO4)(H2O)
      (ThISeO-1) and Th(IO3)2(SeO4) (ThISeO-2). LnISeO-3 and ThISeO-2 crystallize in
      the chiral space group P212121, while LnISeO-1, LnISeO-2, and ThISeO-1
      crystallize in the centrosymmetric space group P21/c. The numbers of both
      coordinating and hydrating water molecules crystallized in LnISeO-1, LnISeO-2,
      and LnISeO-3 increase along these three series, in line with the increasingly
      negative values of hydration enthalpies of heavier trivalent lanthanide ions.
      Such a systematic change in compositions, especially the first coordination
      sphere of Ln, further induces structural rearrangements, including coordination
      number and dimensional reductions. More specifically, the structures of LnISeO-1,
      LnISeO-2, and LnISeO-3 have undergone transitions from 2D Ln-oxo layers with 10
      coordinate Ln centers to 1D Ln-oxo chains with 9-coordinate Ln centers and then
      to 0D Ln-oxo monomers with 8-coordinate Ln centers, respectively. The formation
      and characterization of this large family of Ln/Th iodate selenates suggest that
      such a mixed-anion system not only exhibits richer structural chemistry but also
      can be capable of generating intriguing properties, such as the second-harmonic
      generation (SHG) effect.

PMID- 29345470
TI  - A Bioinspired Cascade Sequence Enables Facile Assembly of
      Methanodibenzo[b,f][1,5]dioxocin Flavonoid Scaffold.
AB  - A remarkable bioinspired EDDA-mediated method for the selective construction of
      biologically interesting and highly strained bridged
      methanodibenzo[b,f][1,5]dioxocin flavonoid scaffold was uncovered by starting
      from a variety of readily available acylphloroglucinol and 2
      hydroxycinnamaldehyde substrates. This method merges a fascinating olefin
      isomerization/hemiacetallization/dehydration/[3 + 3]-type cycloaddition cascade
      reaction driven by an in situ generated chromenylium intermediate and provides a
      convenient and viable synthetic strategy for the efficient access of such
      flavonoid analogues.

PMID- 29345471
TI  - Synthesis and Properties of Dithiafulvenyl Functionalized Spiro[fluorene-9,9'
      xanthene] Molecules.
AB  - Two spiroannulated molecular structures with dithiafulvenyl units functionalized
      at the 2,2',7,7'- (SFX-DTF1) and 2,3',6,'7- (SFX-DTF2) positions of a
      spiro[fluorene-9,9'-xanthene] core were synthesized. Studies revealed the hole
      mobility was significantly influenced by the dithiafulvenyl functionalized
      positions in the molecular structure. To explore their primary applications as
      hole-transporting materials in perovskite solar cells, SFX-DTF1-based devices
      exhibited a power conversion efficiency of 10.67% without the use of p-type
      dopants, yielding good air stability.

PMID- 29345472
TI  - Current-Driven Motion of Domain Boundaries between Skyrmion Lattice and Helical
      Magnetic Structure.
AB  - To utilize magnetic skyrmions, nanoscale vortex-like magnetic structures,
      experimental elucidation of their dynamics against current application in various
      circumstances such as in confined structure and mixture of different magnetic
      phases is indispensable. Here, we investigate the current-induced dynamics of the
      coexistence state of magnetic skyrmions and helical magnetic structure in a thin
      plate of B20-type helimagnet FeGe in terms of in situ real-space observation
      using Lorentz transmission electron microscopy. Current pulses with various
      heights and widths were applied, and the change of the magnetic domain
      distribution was analyzed using a machine-learning technique. The observed
      average driving direction of the two-magnetic-state domain boundary is opposite
      to the applied electric current, indicating ferromagnetic s-d exchange coupling
      in the spin-transfer torque mechanism. The evaluated driving distance tends to
      increase with increasing the pulse duration time, current density (>1 * 109
      A/m2), and sample temperature, providing valuable information about hitherto
      unknown current-induced dynamics of the skyrmion-lattice ensemble.

PMID- 29345473
TI  - Highly Sensitive and Ultrastable Skin Sensors for Biopressure and Bioforce
      Measurements Based on Hierarchical Microstructures.
AB  - Piezoresistive microsensors are considered to be essential components of the
      future wearable electronic devices. However, the expensive cost, complex
      fabrication technology, poor stability, and low yield have limited their
      developments for practical applications. Here, we present a cost-effective,
      relatively simple, and high-yield fabrication approach to construct highly
      sensitive and ultrastable piezoresistive sensors using a bioinspired
      hierarchically structured graphite/polydimethylsiloxane composite as the active
      layer. In this fabrication, a commercially available sandpaper is employed as the
      mold to develop the hierarchical structure. Our devices exhibit fascinating
      performance including an ultrahigh sensitivity (64.3 kPa-1), fast response time
      (<8 ms), low limit of detection of 0.9 Pa, long-term durability (>100 000
      cycles), and high ambient stability (>1 year). The applications of these devices
      in sensing radial artery pulses, acoustic vibrations, and human body motion are
      demonstrated, exhibiting their enormous potential use in real-time healthcare
      monitoring and robotic tactile sensing.

PMID- 29345474
TI  - Total Synthesis of Antiproliferative Parvifloron F.
AB  - The first total synthesis of parvifloron F, a bioactive highly oxidized abietane
      diterpene, was achieved. The abietane skeleton was constructed by Lewis acid
      promoted cyclization. Preliminary structure-activity relationship correlations
      were established for the synthetic intermediates against human tumor cell lines.
      Certain compounds showed unique selective antiproliferative activity against
      triple-negative breast cancer. The oxidation level of the abietane ring affected
      the selectivity.

PMID- 29345475
TI  - Transition-Metal-Free Regiospecific Aroylation of Nitroarenes Using Ethyl
      Arylacetates at Room Temperature.
AB  - A novel regiospecific C(sp3)-C(sp2) coupling between ethyl arylacetates and
      nitroarenes has been developed to deliver biaryl ketones in excellent yields. The
      protocol is metal-free, mild, and compatible with a number of functional groups
      on both of the reacting partners.

PMID- 29345476
TI  - Adapting a parenting intervention for parents aging out of the child welfare
      system: A systematic approach to expand the reach of an evidence-based
      intervention.
AB  - Parents aging out of the child welfare system face a constellation of unique risk
      factors that threaten the well-being of themselves and their children. Although
      parenting interventions are an important resource for providing much-needed
      services to parents aging out, there is currently a lack of evidence-based
      parenting interventions that address the unique needs of this population. The
      purpose of this project was to systematically adapt an evidence-based parenting
      intervention for parents aging out. An established adaptation framework was used
      to guide this process, and acceptability and feasibility outcomes were evaluated
      as part of a pilot study of the adapted intervention. Preliminary intervention
      adaptations included modifications to program delivery and program content. Study
      findings indicated a high level of parent satisfaction with the adapted
      intervention but challenges to feasibility because of inconsistent attendance and
      the substantial effort required for intervention delivery. This study constitutes
      a critical first step toward increasing the reach of evidence-based parenting
      interventions among parents aging out of the child welfare system and underscores
      the need for continued efforts to develop sustainable and effective parenting
      services for this at-risk population. (PsycINFO Database Record

PMID- 29345477
TI  - An exploratory study of stress and coping among Black college men.
AB  - Research on coping mechanisms among Black Americans is robust, yet there is a
      dearth of studies that use qualitative approaches to examine coping specifically
      among young Black men. The current and historical landscape of race relations in
      the United States calls for additional concern and exploration of this topic. To
      fill gaps in this area, this study uncovered the ways Black college men cope with
      various stressors that impact their mental health. Eleven qualitative interviews
      were conducted with 18- to 25-year-old Black men enrolled at a college in the
      Midwest who participated in the Young Black Men, Masculinities, and Mental Health
      (YBMen) project. Data were analyzed using a rigorous and accelerated data
      reduction technique that involved transferring transcript data onto spreadsheets,
      reducing the data, and conducting a rigorous content analysis to generate themes
      and subthemes. Participants reported that Black college men cope with stress by
      discussing their issues with members of their social support networks, engaging
      in physical activities, and relying on themselves. Some respondents reported that
      they intentionally avoided dealing with their mental health, whereas others
      attempted to make sense of their problems. Substance use, violence, and anger
      were all identified as markers of unaddressed stressors. Stigma emerged as a
      barrier to seeking help. Study findings highlight within-group differences among
      Black college men. Mental health researchers must continue to develop creative
      ways to examine stress and coping so that resources can become more culturally
      relevant and readily available both within and outside of the spaces Black men
      occupy. (PsycINFO Database Record

PMID- 29345478
TI  - Racial/ethnic differences of justice-involved youth in substance-related problems
      and services received.
AB  - This study examined differences in substance-related problems and receipt of
      substance-specific counseling in 7 different racial/ethnic groups of justice
      involved youth. Data came from a nationally representative sample of 7,073 youth
      in residential placement across 36 states representing 5 program types.
      Descriptive analyses and regression modeling techniques were used to examine the
      relationship between race/ethnicity, substance problems, and substance services.
      Results show that more than 2/3 report a history of at least 1 substance-related
      problem. Yet, over 12% of youth in residential placement are in programs that do
      not offer any substance-related services. This has the greatest implications for
      African American and Hispanic youth, who are most likely to be the programs
      without these services. Moreover, there are substantive differences in the
      prevalence of substance problems by race and ethnicity. American Indian/Alaska
      Natives and multiracial youth were significantly more likely to have substance
      problems, to be under the influence of drugs and/or alcohol at the time of the
      current offense, to have a history of substance problems and above average mental
      health need, and to have a history of substance problems and a lifetime suicide
      attempt compared to African Americans. Asian youth were similar to African
      Americans and had lower rates of substance problems. Asian youth were also the
      least likely to be under the influence of drugs and/or alcohol at the time of the
      current offense. This study provides important preliminary findings about Asian,
      Native Hawaiian/Pacific Islander, and multiracial justice-involved youth and adds
      to the knowledge about American Indian/Alaska Native populations. (PsycINFO
      Database Record

PMID- 29345479
TI  - Culturally adapted transdiagnostic CBT for SSRI-resistant Turkish adolescents: A
      pilot study.
AB  - The most common mental health problems among adolescents are anxiety and mood
      disorders. While disorder-specific cognitive behavior therapy (CBT) is effective
      for each of these conditions, the comorbidity between anxiety and mood disorders
      indicates a need for the development of evidence-based transdiagnostic
      treatments. To examine the efficacy of culturally adapted transdiagnostic CBT (CA
      CBT) in reducing symptoms of anxiety and depression in treatment-resistant
      Turkish adolescents, 13 adolescent participants with anxiety or mood disorders
      who were treatment resistant received 10 sessions of CA-CBT in group format. The
      main outcome measures were the Screen for Childhood Child Anxiety Related
      Disorders (SCARED), Beck Depression Inventory (BDI), and the Turkish Symptom and
      Syndrome Addendum (TSSA), which were assessed at baseline, posttreatment, and at
      2-month follow-up. At posttreatment, there were large effect sizes for all
      measures: depression scores (BDI, d = .9), anxiety scores (SCARED, d = 1.1), and
      the Turkish Symptom and Syndrome Addendum (TSSA, d = 1.6). Moreover, at 2-month
      follow-up, depression and anxiety symptoms were either maintained or continued to
      improve such that from pretreatment to follow-up the effect sizes were as
      follows: depression scores (BDI, d = 1.4), anxiety scores (SCARED, d = 1.7), and
      the Turkish Symptom and Syndrome Addendum (TSSA, d = 2.4). In addition, there
      were no dropouts across treatment. This open trial suggests that CA-CBT is
      effective in reducing anxiety and depression symptoms and that the treatment is
      well accepted. A full randomized controlled trial to verify the effectiveness of
      transdiagnostic CA-CBT in similar populations is needed. (PsycINFO Database
      Record (c) 2018 APA, all rights reserved).

PMID- 29345480
TI  - Psychometric evaluation of depression measures with Northern Plains Indians.
AB  - Numerous psychometric measurements are used to assess for mental health problems
      in Native American and Alaskan Native (AI/AN) populations; however, few studies
      have been carried out to assess their validity and reliability within these
      populations. This study was designed to assess the validity and reliability of
      numerous measures among the Northern Plains Indians. This article is a partial
      report, focused on the psychometric measures directed at detecting depression,
      namely the Beck Depression Inventory (BDI) II, the Center for Epidemiologic
      Studies Depression (CES-D) Scale, the Tri-Ethnic Depression Scale (TEDS), the
      Beck Hopelessness Scale (BHS), the Beck Anxiety Inventory (BAI), and the Symptom
      Checklist-90-Revised (SCL-90-R). Results revealed moderate to strong correlation
      across all measures, alpha coefficients that exceeded published alphas for the
      general population, and overall indicated their validity and reliability of these
      measures, and a 2-factor solution for the BDI-II. While there were limitations to
      the study, analysis of the results supports the use of each measure with the
      Northern Plains Indians (NPI) subpopulation, that the NPI subpopulation scored
      similar to the general population. (PsycINFO Database Record (c) 2018 APA, all
      rights reserved).

PMID- 29345481
TI  - The influence of low-barrier and voluntary service policies on survivor
      empowerment in a domestic violence housing organization.
AB  - The purpose of community-based domestic violence crisis housing programs (e.g.,
      shelters) is to provide a safe setting that promotes empowerment for survivors of
      intimate partner violence. For staff to reach this aim, the program must have
      formal structures and processes in place to support such efforts. This study
      explored how low-barrier and voluntary service policies influenced staff
      practices and survivor empowerment. Low-barrier policies require that programs
      remove barriers that prevent survivors, particularly those who have mental health
      concerns and/or addictions, from being able to access services. A voluntary
      service policy states that survivors have the right to choose which services, if
      any, they would like to engage in during their stay at the program. Survivors'
      ability to stay at the housing program is not contingent on their participation
      in program services. This exploratory-sequential (QUAL-> quan) mixed-method study
      examined how low-barrier and voluntary service policies influenced staff behavior
      and how these behaviors then related to survivor empowerment. Qualitative results
      revealed that low-barrier and voluntary service were guided by cultural values of
      justice and access, encouraged survivor-centered practices among staff, and were
      believed to promote survivor autonomy. Quantitative results suggested that when
      survivors perceived they had a choice to engage in program services or meet with
      an advocate, their empowerment increased. This study has implications for
      domestic violence organizational practice and provides evidence about the
      contextual factors that support individual empowerment. (PsycINFO Database Record
      (c) 2018 APA, all rights reserved).

PMID- 29345482
TI  - Subjects adjust criterion on errors in perceptual decision tasks.
AB  - The optimal strategy in detection theory is to partition the decision axis at a
      criterion C, labeling all events that score above C "Signal", and all those that
      fall below "Noise." The optimal position of C, C*, depends on signal probability
      and payoffs. If observers place their criterion at some place other than C*, they
      suffer a loss in the Expected Value (EV) of payoffs over the course of many
      decisions. We provide an explicit equation for the degree of loss, where it is
      shown that the falloff in value will be steep in contexts of good discrimination
      and will be a flatter gradient in contexts of poor discrimination. It is these
      gradients of loss in EV that, in theory, drive C toward C*, strongly when
      discrimination is good, weakly when discrimination is poor. When signal
      probabilities or distributions variances are unequal, the basins of attraction
      are asymmetric, so that dynamic adjustments in C will be asymmetric, and thus, as
      we show, will leave it biased. We address our analysis to acquisition speed,
      response variability, discrimination reversal and other aspects of discriminated
      performance. In the final section, we develop an error correction model that
      predicts empirically observed deviations from C* that are inconsistent with the
      standard model, but follow from the proposed model given knowledge of d'.
      (PsycINFO Database Record

PMID- 29345483
TI  - Editorial: Journal article reporting standards.
AB  - In this editorial, the author notes that this issue of American Psychologist
      features a pair of important articles related to newly updated standards for
      reporting research in psychology in scientific journals, covering both
      quantitative (Appelbaum et al., 2018) and qualitative (Levitt et al., 2018)
      research. The increasing breadth and complexity of research, and the importance
      of communicating it effectively, requires user-friendly resources that can be
      applied widely to scientific studies. These two articles are intended to serve
      that purpose, and to encourage thoroughness and accuracy in research reporting,
      for psychologists and other scientists in broader academic communities. The
      articles, known as the Journal Article Reporting Standards (JARS) reports, are
      based on the work of a task force appointed by the American Psychological
      Association (APA) Publications and Communications Board in 2015. (PsycINFO
      Database Record

PMID- 29345484
TI  - Journal article reporting standards for quantitative research in psychology: The
      APA Publications and Communications Board task force report.
AB  - Following a review of extant reporting standards for scientific publication, and
      reviewing 10 years of experience since publication of the first set of reporting
      standards by the American Psychological Association (APA; APA Publications and
      Communications Board Working Group on Journal Article Reporting Standards, 2008),
      the APA Working Group on Quantitative Research Reporting Standards recommended
      some modifications to the original standards. Examples of modifications include
      division of hypotheses, analyses, and conclusions into 3 groupings (primary,
      secondary, and exploratory) and some changes to the section on meta-analysis.
      Several new modules are included that report standards for observational studies,
      clinical trials, longitudinal studies, replication studies, and N-of-1 studies.
      In addition, standards for analytic methods with unique characteristics and
      output (structural equation modeling and Bayesian analysis) are included. These
      proposals were accepted by the Publications and Communications Board of APA and
      supersede the standards included in the 6th edition of the Publication Manual of
      the American Psychological Association (APA, 2010). (PsycINFO Database Record

PMID- 29345485
TI  - Journal article reporting standards for qualitative primary, qualitative meta
      analytic, and mixed methods research in psychology: The APA Publications and
      Communications Board task force report.
AB  - The American Psychological Association Publications and Communications Board
      Working Group on Journal Article Reporting Standards for Qualitative Research
      (JARS-Qual Working Group) was charged with examining the state of journal article
      reporting standards as they applied to qualitative research and with generating
      recommendations for standards that would be appropriate for a wide range of
      methods within the discipline of psychology. These standards describe what should
      be included in a research report to enable and facilitate the review process.
      This publication marks a historical moment-the first inclusion of qualitative
      research in APA Style, which is the basis of both the Publication Manual of the
      American Psychological Association (APA, 2010) and APA Style CENTRAL, an online
      program to support APA Style. In addition to the general JARS-Qual guidelines,
      the Working Group has developed standards for both qualitative meta-analysis and
      mixed methods research. The reporting standards were developed for psychological
      qualitative research but may hold utility for a broad range of social sciences.
      They honor a range of qualitative traditions, methods, and reporting styles. The
      Working Group was composed of a group of researchers with backgrounds in varying
      methods, research topics, and approaches to inquiry. In this article, they
      present these standards and their rationale, and they detail the ways that the
      standards differ from the quantitative research reporting standards. They
      describe how the standards can be used by authors in the process of writing
      qualitative research for submission as well as by reviewers and editors in the
      process of reviewing research. (PsycINFO Database Record

PMID- 29345486
TI  - Facilitating pipeline progress from doctoral degree to first job.
AB  - The sequence of professional development within psychology from doctoral
      education to first job represents a period of remarkable professional and
      personal growth for each trainee. However, this sequence also contains a variety
      of barriers that hinder progress through the pipeline. The myriad individual-,
      program-, and system-level barriers encountered by trainees in health
      service/other applied service psychology and in research basic/applied psychology
      are identified. To actively and systematically facilitate improved passage
      through major transition points, individual trainee and trainer, program- and
      system-level action steps are recommended. In addition, emphasis is placed on
      ensuring that the psychology education and training culture prioritizes the
      progress, creativity, and flourishing of trainees and supports their movement
      through branching pipelines in their training and in their careers. (PsycINFO
      Database Record

PMID- 29345487
TI  - On the general acceptance of confessions research: Opinions of the scientific
      community.
AB  - Eighty-seven experts on the psychology of confessions-many of whom were highly
      published, many with courtroom experience-were surveyed online about their
      opinions on 30 propositions of relevance to deception detection, police
      interrogations, confessions, and relevant general principles of psychology. As
      indicated by an agreement rate of at least 80%, there was a strong consensus that
      several findings are sufficiently reliable to present in court. This list
      includes but is not limited to the proposition that the risk of false confessions
      is increased not only by explicit threats and promises but by 2 common
      interrogation tactics-namely, the false evidence ploy and minimization tactics
      that imply leniency by offering sympathy and moral justification. Experts also
      strongly agreed that the risk of undue influence is higher among adolescents,
      individuals with compliant or suggestible personalities, and those with
      intellectual impairments or diagnosed psychological disorders. Additional
      findings indicated that experts set a high standard before judging a proposition
      to be sufficiently reliable for court-and an even higher standard on the question
      "Would you testify?" Regarding their role as scientific experts, virtually all
      respondents stated that their primary objective was to educate the jury and that
      juries are more competent at evaluating confession evidence with assistance from
      an expert than without. These results should assist trial courts and expert
      witnesses in determining what aspects of the science are generally accepted and
      suitable for presentation in court. (PsycINFO Database Record

PMID- 29345488
TI  - Risky business: Correlation and causation in longitudinal studies of skill
      development.
AB  - Developmental theories often posit that changes in children's early psychological
      characteristics will affect much later psychological, social, and economic
      outcomes. However, tests of these theories frequently yield results that are
      consistent with plausible alternative theories that posit a much smaller causal
      role for earlier levels of these psychological characteristics. Our article
      explores this issue with empirical tests of skill-building theories, which
      predict that early boosts to simpler skills (e.g., numeracy or literacy) or
      behaviors (e.g., antisocial behavior or executive functions) support the long
      term development of more sophisticated skills or behaviors. Substantial
      longitudinal associations between academic or socioemotional skills measured
      early and then later in childhood or adolescence are often taken as support of
      these skill-building processes. Using the example of skill-building in
      mathematics, we argue that longitudinal correlations, even if adjusted for an
      extensive set of baseline covariates, constitute an insufficiently risky test of
      skill-building theories. We first show that experimental manipulation of early
      math skills generates much smaller effects on later math achievement than the
      nonexperimental literature has suggested. We then conduct falsification tests
      that show puzzlingly high cross-domain associations between early math and later
      literacy achievement. Finally, we show that a skill-building model positing a
      combination of unmeasured stable factors and skill-building processes can
      reproduce the pattern of experimental impacts on children's mathematics
      achievement. Implications for developmental theories, methods, and practice are
      discussed. (PsycINFO Database Record

PMID- 29345496
TI  - Feedback from the European Bioanalysis Forum: focus workshop on current analysis
      of immunogenicity: best practices and regulatory hurdles.
AB  - European Bioanalysis Forum Workshop, Lisbon, Portugal, September 2016: At the
      recent European Bioanalysis Forum Focus Workshop, 'current analysis of
      immunogenicity: best practices and regulatory hurdles', several important
      challenges facing the bioanalytical community in relation to immunogenicity
      assays were discussed through a mixture of presentations and panel sessions. The
      main areas of focus were the evolving regulatory landscape, challenges of assay
      interferences from either drug or target, cut-point setting and whether
      alternative assays can be used to replace neutralizing antibody assays. This
      workshop report captures discussions and potential solutions and/or
      recommendations made by the speakers and delegates.

PMID- 29345497
TI  - Experiences of menopause, self-management strategies for menopausal symptoms and
      perceptions of health care among immigrant women: a systematic review.
AB  - OBJECTIVE: To systematically review the published literature relating to
      experiences of menopause, self-management strategies for menopausal symptoms and
      health-care needs among immigrant women. METHODS: A systematic literature search
      of English-language publications was performed using Medline, Embase, PsychInfo,
      Cinahl and Scopus. Twenty-four papers reporting on 19 studies met our inclusion
      criteria and investigated immigrant women's experiences of menopause and/or their
      self-management strategies for menopausal symptoms and/or their perceptions of
      menopause-specific health care. FINDINGS: Of the 19 studies, 15 reported symptoms
      experienced during the menopausal transition. Three studies included questions
      regarding self-management strategies for menopausal symptoms and four enquired
      about perceptions of menopause-specific health care. Although the heterogeneity
      of the studies makes comparison difficult, their findings are broadly consistent.
      Immigrant women reported more vasomotor symptoms and other physical symptoms and
      poorer mental health than non-immigrant women. The few studies that investigated
      self-management strategies for menopausal symptoms found that these were
      influenced by culture and those that assessed perceptions of menopause-specific
      health care found that they were mostly dissatisfied with the care they had
      received. CONCLUSION: More research is needed to improve understanding of how
      immigrant women manage the menopausal transition and how to provide culturally
      relevant menopause-specific health care.

PMID- 29345498
TI  - Effects of blueberry and cranberry consumption on type 2 diabetes glycemic
      control: A systematic review.
AB  - The metabolic effects of cranberry and blueberry consumption on glycemic control
      have been evaluated in vitro and in animal models as well as in human studies,
      although findings have not been systematically reviewed yet. Therefore, a
      systematic review was carried out of relevant randomized clinical trials (RCTs)
      in order to assess the effect of berries (blueberry and cranberry) consumption on
      type 2 diabetes (T2DM) glycemic control. Some evidences were also discussed on
      the anti-diabetic mechanisms exerted by berries polyphenols. Studies were
      identified by searching electronic databases: LILACS, PubMed/MEDLINE, Scopus, The
      Cochrane Library and Web of Science. Three authors independently searched and
      extracted RCTs in which the effect of berries (cranberry or blueberry)
      consumption on T2DM glycemic control was assessed. A total of 7 RCTs, involving
      270 adults with type 2 diabetes were included. Despite the heterogeneity of the
      administration forms (in natura, dried, extract, preparations - juice), dosage,
      duration of the intervention and type of population of the studies involving
      these two berries some studies highlight the potential benefit of berries,
      especially of blueberry, on glucose metabolism in T2DM subjects. Daily cranberry
      juice (240 mL) consumption for 12 weeks and blueberry extract or powder
      supplementation (9.1 to 9.8 mg of anthocyanins, respectively) for 8 to 12 weeks
      showed a beneficial effect on glucose control in T2DM subjects. Those results
      indicate a promising use of these berries in T2DM management; although more
      studies are required to better understand the mechanisms involved.

PMID- 29345499
TI  - Disrupted behaviour in grammatical morphology in French speakers with autism
      spectrum disorders.
AB  - Mixed and inconsistent findings have been reported across languages concerning
      grammatical morphology in speakers with Autism Spectrum Disorders (ASD). Some
      researchers argue for a selective sparing of grammar whereas others claim to have
      identified grammatical deficits. The present study aimed to investigate this
      issue in 26 participants with ASD speaking European French who were matched on
      age, gender and SES to 26 participants with typical development (TD). The groups
      were compared regarding their productivity and accuracy of syntactic and
      agreement categories using the French MOR part-of-speech tagger available from
      the CHILDES. The groups significantly differed in productivity with respect to
      nouns, adjectives, determiners, prepositions and gender markers. Error analysis
      revealed that ASD speakers exhibited a disrupted behaviour in grammatical
      morphology. They made gender, tense and preposition errors and they omitted
      determiners and pronouns in nominal and verbal contexts. ASD speakers may have a
      reduced sensitivity to perceiving and processing the distributional structure of
      syntactic categories when producing grammatical morphemes and agreement
      categories. The theoretical and cross-linguistic implications of these findings
      are discussed.

PMID- 29345500
TI  - Effects of L-Arginine Supplementation on Leukogram, Inflammatory Bowel
      Infiltrates and Immunoglobulins with 5-FU Use in Rats.
AB  - This study evaluated the effects of L-arginine supplementation on blood
      parameters, kidney and liver function, immunoglobulins and noninflammatory
      infiltrates in the small intestines of rats subjected to chemotherapy with 5
      fluorouracil (5-FU). Thirty-two Wistar rats were randomly distributed into 4
      groups (8 rats/group): an untreated control group, and test groups receiving one
      dose of 5-FU (G5-FU group), one dose of 5-FU and 295 mg L-arginine/day (GArg295
      group) or one dose of 5-FU and 458 mg L-arginine/day (GArg458 group). Neutrophil
      count, platelet count, serum IgA, and fibrinogen levels in GArg295 and GArg458
      remained within normal limits after chemotherapy. In addition, in GArg458 the
      inflammatory bowel infiltrates improved in 57% of the rats, which showed mild
      inflammation. The results suggest that daily supplementation with 295 or 458 mg L
      arginine attenuates the side effects of 5-FU, including thrombocytopenia and
      neutropenia, and modulates IgA production. Supplementation with 458 mg of L
      arginine/day can also reduce mucositis levels in the small intestine after 5-FU
      chemotherapy.

PMID- 29345501
TI  - 'It's nothing you could ever prepare anyone for': the experiences of young people
      and their families following parental stroke.
AB  - AIMS: This study sought to explore the experiences of young people (aged 8-16)
      and their families following parental acquired brain injury (ABI), with the aim
      of developing an understanding of the ways in which members of a family make
      sense of events post-injury, and to consider the implications of different
      perspectives on adjustment and coping. DESIGN: The study applied a qualitative
      approach using a thematic analysis methodology. PROCEDURE: Individual semi
      structured interviews were conducted with 10 individuals from three families
      affected by parental stroke. RESULTS: Findings suggested that post-injury,
      families experienced a period of uncertainty in which they were required to
      renegotiate their roles and adjust to the loss associated with parental stroke.
      Additionally, the psychosocial wellbeing of young people was negatively affected,
      whilst protective and coping strategies were recognised. CONCLUSIONS: The
      research offers an insight into the processes that may contribute to patterns of
      interpersonal relating that could negatively impact on adjustment. Provision of
      adequate information, psychological and practical support during recovery may
      therefore be crucial elements of supporting young people and their families in
      adjusting to the challenges posed by stroke.

PMID- 29345502
TI  - Extended 3D and 4D cumulative plots for evaluation of unmatched incurred sample
      reanalysis.
AB  - AIM: Incurred sample reanalysis (ISR) helps ensure the reliability of
      pharmacokinetic studies. An appropriate graph may facilitate the evaluation of an
      unmatched reanalyses or a failed ISR test. METHODS: We evaluated different ways
      of visualizing multidimensional ISR data using an extended cumulative ISR plot.
      RESULTS: 3D and 4D cumulative ISR plots enable comprehensive data analysis using
      a single plot. We propose to use color for percentage difference classes in bar
      and XY-scatter plots. For the latter the shape of symbols may represent analyte
      concentration class, study phase, analyst or subject. CONCLUSION: The extended 3D
      and 4D cumulative ISR plots facilitate in-study monitoring and post-study
      inspection of data. It helps find the root cause of unmatched ISR, thus
      increasing reliability of bioanalytical data.

PMID- 29345503
TI  - Effectiveness of the Biophysical Barriers to the Peridural Fibrosis in Rat
      Laminectomy Model.
AB  - PURPOSE: Peridural fibrosis which could occur after the spinal surgery could
      adhere neural tissue closely and may cause to neural entrapment symptoms and
      require surgical reintervention. AIM OF THE STUDY: Present study was designed to
      reduce occurrence of peridural fibrosis in rat laminectomy model by using
      biophysical barriers called hyaluronic acid (HAS) dural barrier, activated
      polyethylene glycol and polyethylene imine (PEG) dural barrier, and platelet-rich
      plasma (PRP). MATERIALS AND METHODS: In this study, 2 of 26 male Wistar albino
      rats (325-350 g body weight), which were not included into study groups were
      sacrificed by removing their total blood and their blood was used for preparation
      of PRP, and remaining rats were randomly delivered into four groups called SHAM,
      HAS, PEG, and PRP groups. Then L3-4-5 laminectomy was performed to all animals
      and experimental agents were administered to the selected groups mentioned above.
      Spinal colons of all animals were removed gross total after 6-week period and
      investigated histopathologically. Additionally, real-time-polymerase chain
      reaction was used to obtain collagen type I and type III, transforming growth
      factor-1beta, and tumor necrosis factor-alpha gene expressions. RESULTS: All
      results demonstrated that polyethylene glycol and polyethylene imine dural
      barrier and PRP could decrease peridural fibrosis formation efficiently in rat.
      CONCLUSION: Present study results suggested that to reduce or block formation of
      peridural fibrosis, either polyethylene glycol and polyethylene imine dural
      barrier or PRP could be used effectively in human subjects after they will be
      closely investigated in future studies.

PMID- 29345504
TI  - Development of the HOOSglobal to Assess Patient-Reported Outcomes in Patients
      Undergoing Hip Preservation Procedures.
AB  - BACKGROUND: The creation of a single patient-reported outcome (PRO) platform
      validated across hip preservation, osteoarthritis (OA), and total hip
      arthroplasty (THA) populations may reduce barriers and streamline the routine
      collection of PROs in clinical practice. As such, the purpose of this study was
      to determine if augmenting the Hip disability and Osteoarthritis Outcome Score
      Joint Replacement (HOOS, JR) with additional HOOS questions would result in a PRO
      platform that could be used across a wider spectrum of hip patient populations.
      HYPOTHESIS: The HOOS, JR would demonstrate a notable ceiling effect, but by
      augmenting the HOOS, JR with additional HOOS questions, a responsive PRO platform
      could be created. STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 2.
      METHODS: Using preoperative and postoperative HOOS responses from a sample of 304
      patients undergoing periacetabular osteotomy (PAO), additional items were
      identified to augment the HOOS, JR. The psychometric properties of a newly
      created PRO tool (HOOSglobal) were then compared with the HOOS, JR and other PRO
      instruments developed for patients with hip OA and/or undergoing THA. RESULTS: By
      augmenting the HOOS, JR with 2 additional questions, the HOOSglobal was more
      responsive than all other included PRO tools and had significantly fewer maximum
      postoperative scores than the HOOS, JR ( P < .0001), HOOS-Physical Function Short
      form ( P < .0001), Western Ontario and McMaster Universities Osteoarthritis Index
      ( P = .02), University of California, Los Angeles activity scale ( P = .0002),
      and modified Harris Hip Score ( P = .04). The postoperative HOOSglobal score
      threshold associated with patients achieving the patient acceptable symptom state
      (PASS) was 62.5. CONCLUSION: The HOOSglobal is a valid and responsive PRO tool
      after PAO and may potentially provide the orthopaedic community with a PRO
      platform to be used across hip-related subspecialties. For patients undergoing
      PAO, a postoperative HOOSglobal score >=62.5 was associated with patients
      achieving the PASS.

PMID- 29345505
TI  - The pharmacological management of metabolic syndrome.
AB  - INTRODUCTION: The metabolic syndrome includes a constellation of several well
      established risk factors, which need to be aggressively treated in order to
      prevent overt type 2 diabetes and cardiovascular disease. While recent guidelines
      for the treatment of individual components of the metabolic syndrome focus on
      cardiovascular benefits as resulted from clinical trials, specific recent
      recommendations on the pharmacological management of metabolic syndrome are
      lacking. The objective of present paper was to review the therapeutic options for
      metabolic syndrome and its components, the available evidence related to their
      cardiovascular benefits, and to evaluate the extent to which they should
      influence the guidelines for clinical practice. Areas covered: A Medline
      literature search was performed to identify clinical trials and meta-analyses
      related to the therapy of dyslipidemia, arterial hypertension, glucose metabolism
      and obesity published in the past decade. Expert commentary: Our recommendation
      for first-line pharmacological are statins for dyslipidemia, renin-angiotensin
      aldosteron system inhibitors for arterial hypertension, metformin or
      sodium/glucose cotransporter 2 inhibitors or glucagon-like peptide 1 receptor
      agonists (GLP-1RAs) for glucose intolerance, and the GLP-1RA liraglutide for
      achieving body weight and waist circumference reduction.

PMID- 29345506
TI  - Effects of physical and depressive symptoms on the sexual life of Turkish women
      in the climacteric period.
AB  - OBJECTIVE: To assess the effects of physical and depressive symptoms on the
      sexual life of women in the climacteric period. METHODS: This study was conducted
      with 572 women at a university hospital. The Beck Depression Inventory (BDI),
      Menopause Rating Scale (MRS) and Female Sexual Function Index (FSFI) were used to
      evaluate depressive symptoms, intensity of menopausal symptoms and sexual
      function. RESULTS: Sexual dysfunction and depressive symptoms were determined in
      86.4% and 54.9% of the women, respectively. In univariate analysis, women without
      health insurance, with low income, being married for longer than 21 years and
      being in menopause had low FSFI but high BDI and MRS scores. In multiple
      regression analysis, advanced age of women, women with low income, unemployed
      women, low educated women and their husbands and women with depressive symptoms
      had low FSFI scores. There was a negative relationship between total FSFI and MRS
      and BDI scores. CONCLUSION: Determination and treatment of sexual, emotional and
      physical problems in the climacteric period are very important for the
      improvement of the quality of life of women.

PMID- 29345508
TI  - Response by Twin Italian Hub Hospitals in a Double Seismic Event: A Retrospective
      Observational Investigation.
AB  - INTRODUCTION: The objectives of this study were to compare prevalence rates of
      different pathologies, ambulance system and emergency department management
      times, and patient survival and hazard ratios for codes 2 and 3 in two hub
      hospitals in Modena in the 36-month period across the stages of two major
      earthquakes in short sequence in Northern Italy in 2012. METHODS: Clinical
      records pertaining to the emergency care of patients were analyzed and only those
      assigned status codes 2 and 3 by ambulance professionals were included (if the
      assessment was confirmed by emergency department triage). The statistical
      analysis of data was divided by three time periods studied: before,
      during/between, and after the earthquakes. RESULTS: Among the 2,278 retained
      records, there were no statistically significant differences in the prevalence of
      the main pathologies presented at the two hubs in the studied period. A Cox
      regression model was used to analyze the survival of patients in the different
      stages of the emergency; there were no statistically significant differences in
      the hazard ratios of death before, during, and after the earthquake. The study
      found a significant increase in emergency department treatment times. DISCUSSION:
      Redundancies in the Modena medical system were found to have compensated for
      damaged hospital facilities. In particular, they helped emergency systems
      reorganize themselves faster in order to bring medical assistance to people
      during and around seismic events with as a minimal amount of disruption as
      possible. CONCLUSION: The Modena medical system was redundant and ensured that
      disrupted emergency systems were reorganized and put back online while damaged
      hospital facilities were compensated for/reproduced elsewhere.

PMID- 29345509
TI  - Corrigendum.

PMID- 29345507
TI  - Ovarian tissue cryopreservation in young females through the Oncofertility
      Consortium's National Physicians Cooperative.
AB  - AIM: To characterize the clinical indications of females (<15 years old)
      undergoing ovarian tissue cryopreservation (OTC) through the Oncofertility
      Consortium's National Physicians Cooperative (OC-NPC). PATIENTS & METHODS: The
      clinical indications of 114 females who underwent OTC were classified, and their
      incidence was compared with childhood cancer databases. RESULTS:
      Leukemias/myeloproliferative diseases/myelodysplastic diseases and
      hemoglobinopathies were the most prevalent oncologic and nononcologic indications
      for OTC, respectively. The frequencies of malignant bone tumors and soft tissue
      and other extraosseous sarcomas were higher in the OC-NPC cohort relative to the
      general population, while CNS/intracranial/intraspinal neoplasms, retinoblastoma
      and hepatic tumors were lower. CONCLUSION: Those opting for OTC through the OC
      NPC are at highest fertility risk, indicating that the appropriate patient
      populations are being identified. [Formula: see text].

PMID- 29345510
TI  - Preliminary Evaluation of the Viability of Peritoneal Drainage Catheters
      Implanted in Rats for Extended Durations.
AB  - : Purpose/Aim: In developing a novel peritoneal oxygenation therapy, catheters
      implanted into the peritoneal cavity became obstructed with omental tissue and
      prevented the infusion and removal of fluid from the peritoneal cavity. The
      obstruction of peritoneal catheters is a significant failure in researching
      various peritoneal treatments as further fluid administration is no longer
      possible. The purpose of this preliminary study was to determine the most
      effective catheter design for infusion and removal of fluid into the peritoneal
      cavity of rats. MATERIALS AND METHODS: Four types of catheters were tested
      including the Jackson-Pratt, round fluted drain, flat fluted drain, and an
      original design. Three of each catheter type were surgically placed into the
      peritoneal cavity of rats (n = 12). In order to test the efficacy of each
      catheter, saline was infused and extracted twice daily. Catheters were scored on
      a weighted scale based on the amount of time they remained patent, the subjective
      force needed for extraction/infusion, and the amount of saline removed. RESULTS:
      The round and flat fluted drain catheters remained patent for the full duration
      of the study (12 days) compared to the other models which failed after 7 days.
      These catheters also yielded a high average for extracted saline volume and an
      easy extraction/infusion. CONCLUSIONS: The round and flat fluted drain catheters
      were recognized as viable options to be used in rats for peritoneal drain studies
      of up to 12 days.

PMID- 29345511
TI  - Clinical Characteristics of Herpes Simplex Virus Associated Anterior Uveitis.
AB  - PURPOSE: The aim of this study is to describe the clinical characteristics of
      molecularly proven Herpes simplex virus (HSV) anterior uveitis. METHODS: The
      literature on HSV anterior uveitis whereby the diagnosis was confirmed by
      polymerase chain reaction (PCR) and or Goldmann-Witmer coefficient in aqueous
      humor was reviewed. Three studies from Europe and one from Japan could be
      included. RESULTS: It was observed that HSV anterior uveitis is mostly an acute
      unilateral disease mainly occurring in middle-aged people with a predominance in
      females. The incidence of keratitis in HSV is between 33 and 41%. High
      intraocular pressure is frequently observed and ranged from 46 to 90%. Sectorial
      iris atrophy may be absent, especially early in the disease. CONCLUSION: The
      clinical characteristics of HSV anterior uveitis can mimic other viral and non
      infectious anterior uveitis entities especially at onset. Aqueous humor analysis
      for PCR and GWC can be useful in case of suspected viral uveitis.

PMID- 29345512
TI  - Physical Activity, Function, and Mortality in Advanced Age: A Longitudinal Follow
      Up (LiLACS NZ).
AB  - The relationship between physical activity, function, and mortality is not
      established in advanced age. Physical activity, function, and mortality were
      followed in a cohort of Maori and non-Maori adults living in advanced age for a
      period of 6 years. Generalized linear regression models were used to analyze the
      association between physical activity and Nottingham Extended Activities of Daily
      Living scale, whereas Kaplan-Meier survival analysis and Cox proportional hazard
      models were used to assess the association between the physical activity and
      mortality. The hazard ratio for mortality for those in the least active physical
      activity quartile was 4.1 for Maori and 1.8 for non-Maori compared with the most
      active physical activity quartile. There was an inverse relationship between
      physical activity and mortality, with lower hazard ratios for mortality at all
      levels of physical activity. Higher levels of physical activity were associated
      with lower mortality and higher functional status in advanced-aged adults.

PMID- 29345513
TI  - No Benefit in Neurologic Outcomes of Survivors of Out-of-Hospital Cardiac Arrest
      with Mechanical Compression Device.
AB  - INTRODUCTION: Out-of-hospital cardiac arrest (OHCA) is a major cause of death and
      morbidity in the United States. Quality cardiopulmonary resuscitation (CPR) has
      proven to be a key factor in improving survival. The aim of our study was to
      investigate the outcomes of OHCA when mechanical CPR (LUCAS 2 Chest Compression
      SystemTM) was utilized compared to conventional CPR. Although controlled trials
      have not demonstrated a survival benefit to the routine use of mechanical CPR
      devices, there continues to be an interest for their use in OHCA. METHODS: We
      conducted a retrospective observational study of OHCA comparing the outcomes of
      mechanical and manual chest compressions in a fire department based EMS system
      serving a population of 1.4 million residents. Mechanical CPR devices were
      geographically distributed on 11 of 33 paramedic ambulances. Data were collected
      over a 36-month period and outcomes were dichotomized based on utilization of
      mechanical CPR. The primary outcome measure was survival to hospital discharge
      with a cerebral performance category (CPC) score of 1 or 2. RESULTS: This series
      had 3,469 OHCA reports, of which 2,999 had outcome data and met the inclusion
      criteria. Of these 2,236 received only manual CPR and 763 utilized a mechanical
      CPR device during the resuscitation. Return of spontaneous circulation (ROSC) was
      attained in 44% (334/763) of the mechanical CPR resuscitations and in 46%
      (1,020/2,236) of the standard manual CPR resuscitations (p = 0.32). Survival to
      hospital discharge was observed in 7% (52/763) of the mechanical CPR
      resuscitations and 9% (191/2,236) of the manual CPR group (p = 0.13). Discharge
      with a CPC score of 1 or 2 was observed in 4% (29/763) of the mechanical CPR
      resuscitation group and 6% (129/2,236) of the manual CPR group (p = 0.036).
      CONCLUSIONS: In our study, use of the mechanical CPR device was associated with a
      poor neurologic outcome at hospital discharge. However, this difference was no
      longer evident after logistic regression adjusting for confounding variables.
      Resuscitation management following institution of mechanical CPR, specifically
      medication and airway management, may account for the poor outcome reported.
      Further investigation of resuscitation management when a mechanical CPR device is
      utilized is necessary to optimize survival benefit.

PMID- 29345514
TI  - Design and Validation of an Instrumented Uneven Terrain Treadmill.
AB  - Studying human and animal locomotion on an uneven terrain can be beneficial to
      basic science and applied studies for clinical and robotic applications.
      Traditional biomechanical analysis of human locomotion has often been limited to
      laboratory environments with flat, smooth runways and treadmills. The authors
      modified a regular exercise treadmill by attaching wooden blocks to the treadmill
      belt to yield an uneven locomotion surface. To ensure that these treadmill
      modifications facilitated biomechanical measurements, the authors compared ground
      reaction force data collected while a subject ran on the modified instrumented
      treadmill with a smooth surface with data collected using a conventional
      instrumented treadmill. Comparisons showed only minor differences. These results
      suggest that adding an uneven surface to a modified treadmill is a viable option
      for studying human or animal locomotion on an uneven terrain. Other types of
      surfaces (eg, compliant blocks) could be affixed in a similar manner for studies
      on other types of locomotion surfaces.

PMID- 29345515
TI  - Safety of biologic agents for psoriasis in patients with viral hepatitis.
AB  - INTRODUCTION: Biologics are highly effective, important treatment options for
      moderate-to-severe psoriasis. Biologics are well tolerated and have few side
      effects. However, the use of biologics in patients with concomitant chronic viral
      hepatitis is debatable. Recent reports have suggested a very low associated risk
      of reactivation of chronic hepatitis B (HBV) and C (HCB). OBJECTIVE: To evaluate
      the safety and effectiveness of biologics for moderate to severe psoriasis
      patients with concomitant chronic viral hepatitis. METHODS: We followed 39
      patients with psoriasis and concurrent chronic viral hepatitis (chronic inactive
      and occult cases) with no clinical signs and/or lab indication of active liver
      disease) treated with biologic agents for at least 24 weeks. Patients were
      regularly monitored for reactivation of viral hepatitis with liver enzymes, viral
      DNA load, and viral markers. RESULTS: There was no evidence of viral reactivation
      until the last available lab investigation results (done three months after
      stopping the medication). None of the patients showed signs or symptoms of liver
      failure. CONCLUSION: The use of biologic therapy appeared safe and effective in
      this small cohort of selected patients with chronic HBV and HCV infection. Close
      monitoring for HBV and HCV viral load is recommended for patients with high-risk
      factors.

PMID- 29345516
TI  - Association between Weather-Related Factors and Cardiac Arrest of Presumed
      Cardiac Etiology: A Prospective Observational Study Based on Out-of-Hospital Care
      Data.
AB  - OBJECTIVE: The objective of this study was to determine the association between
      weather-related factors and out-of-hospital cardiac arrest (OHCA) of presumed
      cardiac etiology. METHODS: This was a prospective observational study performed
      in a prehospital setting. Data from the Emergency Medical Service in Hamburg
      (Germany) and data from the local weather station were evaluated over a 5-year
      period. Weather data (temperature, humidity, air pressure, wind speed) were
      obtained every minute and matched with the associated rescue mission data. Lowess
      Regression analysis was performed to assess the relationship between the above
      mentioned weather-related factors and OHCA of presumed cardiac etiology.
      Additionally, varying measuring-ranges were defined for each weather-related
      factor in order to compare them with each other with regard to the probability of
      occurrence of OHCA. RESULTS: During the observation period 1,558 OHCA with
      presumed cardiac etiology were registered (age: 67 +/- 19 yrs; 62% male; hospital
      admission: 37%; survival to hospital discharge: 6.7%). Compared to moderate
      temperatures (5 - 25 degrees C), probability of OHCA-occurrence increased
      significantly at temperatures above 25 degrees C (p = 0.028) and below 5 degrees
      C p = 0.011). Regarding air humidity, probability of OHCA-occurrence increased
      below a threshold-value of 75% compared to values above this cut-off (p = 0.006).
      Decreased probability was seen at moderate atmospheric pressure (1000 hPa - 1020
      hPa), whereas increased probability was seen above 1020 hPa (p = 0.023) and below
      1000 hPa (p = 0.035). Probability of OHCA-occurrence increased continuously with
      increasing wind speed (p < 0.001). CONCLUSIONS: There are associations between
      several weather-related factors such as temperature, humidity, air pressure, and
      wind speed, and occurrence of OHCA of presumed cardiac etiology. Particularly
      dangerous seem to be cold weather, dry air and strong wind.

PMID- 29345517
TI  - PET-adapted therapy for advanced Hodgkin lymphoma - systematic review.
AB  - INTRODUCTION: Positron emission tomography-computed tomography (PET-CT) performed
      after two chemotherapy cycles (PET-2) has become an accepted prognostic tool in
      Hodgkin lymphoma (HL). We evaluated the effect of PET-adapted strategy on outcome
      in advanced stage HL. METHODS: In August 2017, we searched electronic databases,
      conference proceedings and ongoing trials. We included all studies in which
      treatment modification for advanced HL was performed based on the results of the
      interim PET scan. The primary analysis included randomized controlled trials
      (RCTs). Outcomes were progression-free survival (PFS) and overall survival (OS).
      RESULTS: We identified 13 studies (4 RCTs, 7 phase II and 2 retrospective
      studies), conducted between 1999 and 2014, including 6856 patients. Of the four
      RCTS: one used therapy escalation, one did de-escalation and two trials performed
      both. Outcomes were assessed at different time point between 2 and 5 years. Three
      RCTs for de-escalating therapy, obtained similar outcomes despite reducing
      therapy, with a 2-year PFS of 88-92% (6 escalated BEACOPP (EB) vs. 4 ABVD
      cycles), a 5-year PFS of 91-92% (6/8 EB vs. 4 EB cycles) and a 5-year PFS of 80
      82% (6 ABVD vs. omitting bleomycin after two successful ABVD cycles). Two RCTs
      implemented escalation. The randomization was between adding rituximab or not. In
      both trials, it did not affect outcome, with a 4-year PFS of 68-69% (addition of
      rituximab to BEACOPP after 2 ABVD cycles) and 5-year PFS of 88-90% (addition of
      rituximab to EB after 2 EB cycles). Performing true randomization between PET
      adapted and a standard ABVD control arm was not feasible, given historical data.
      CONCLUSIONS: This systematic review of PET-adapted therapy, mainly based on RCTs,
      suggests that a change to the treatment paradigm is appropriate in advanced HL.

PMID- 29345518
TI  - Bacterial pathogenesis and interleukin-17: interconnecting mechanisms of immune
      regulation, host genetics, and microbial virulence that influence severity of
      infection.
AB  - Interleukin-17 (IL-17) is a pro-inflammatory cytokine involved in the control of
      many different disorders, including autoimmune, oncogenic, and diverse infectious
      diseases. In the context of infectious diseases, IL-17 protects the host against
      various classes of microorganisms but, intriguingly, can also exacerbate the
      severity of some infections. The regulation of IL-17 expression stems, in part,
      from the activity of Interleukin-23 (IL-23), which drives the maturation of
      different classes of IL-17-producing cells that can alter the course of
      infection. In this review, we analyze IL-17/IL-23 signalling in bacterial
      infection, and examine the interconnecting mechanisms that link immune
      regulation, host genetics, and microbial virulence in the context of bacterial
      pathogenesis. We consider the roles of IL-17 in both acute and chronic bacterial
      infections, with a focus on mouse models of human bacterial disease that involve
      infection of mucosal surfaces in the lungs, urogenital, and gastrointestinal
      tracts. Polymorphisms in IL-17-encoding genes in humans, which have been
      associated with heightened host susceptibility to some bacterial pathogens, are
      discussed. Finally, we examine the implications of IL-17 biology in infectious
      diseases for the development of novel therapeutic strategies targeted at
      preventing bacterial infection.

PMID- 29345519
TI  - "I Just Roll Over, Pick Myself Up, and Carry On!" Exploring the Fall-Risk
      Experience of Canadian Masters Athletes.
AB  - OBJECTIVES: The risk of falling increases in adults aged 65 years and older. A
      common barrier to take up physical activity in sedentary older adults is the fear
      of falls and injury. Experiences of master athletes can provide insights into
      management of the risk of falling. The purpose of this phenomenological study was
      to explore the fall-risk experience of masters athletes actively competing in
      sport. METHODS: Masters athletes aged 55 years and older (N = 22) described their
      experiences in semistructured interviews. Data were analyzed through an
      interpretive-constructivist paradigm using inductive content analysis. RESULTS:
      Five dominant themes emerged: acceptance, learning, awareness, resilience, and
      self-fulfillment. Participants of this study reported an acceptance of the risk
      they take in sport for falls and injuries in their pursuits for self-fulfillment.
      DISCUSSION: Findings indicate that master athletes accept the risk for falls and
      injuries in sport, find ways to adapt, and continue to compete because it is self
      fulfilling. Sharing their experiences might inspire other older adults to get
      active as a rewarding means of remaining independent.

PMID- 29345520
TI  - Correlates of Physical Activity Among Middle-Aged and Older Adults With Hazardous
      Drinking Habits in Six Low- and Middle-Income Countries.
AB  - We investigated physical activity (PA) correlates among middle-aged and older
      adults (aged >=50 years) with hazardous drinking patterns in six low- and middle
      income countries. Cross-sectional data were analyzed from the World Health
      Organization's Study on Global Ageing and Adult Health. Hazardous drinking was
      defined as consuming >7 (females) or >14 (males) standard drinks per week.
      Participants were dichotomized into low (i.e., not meeting 150 min of moderate
      PA/week) and moderate-high physically active groups. Associations between PA and
      a range of correlates were examined using multivariable logistic regressions. The
      prevalence of low PA in 1,835 hazardous drinkers (60.5 +/- 13.1 years; 87.9%
      males) was 16.2% (95% confidence interval [13.9%, 18.9%]). Older age, living in
      an urban setting, being unemployed, depression, underweight, obesity, asthma,
      visual impairment, poor self-rated health, and higher levels of disability were
      identified as significant PA correlates. The current data provide important
      guidance for future interventions to assist older hazardous drinkers to engage in
      regular PA.

PMID- 29345521
TI  - Development and validation of an ELISA to study panitumumab pharmacokinetics.
AB  - AIM: Panitumumab is a monoclonal antibody directed against EGFR that is approved
      for the treatment of metastatic colorectal cancer. To investigate its
      pharmacokinetics and concentration-response relationship, a validated assay is
      required. RESULTS: An ELISA assay was developed and validated according to
      international recommendations. Six calibrators (ranging from 0.1 to 20 mg/l) plus
      one anchor point (50 mg/l) and three quality controls (0.45, 2 and 8 mg/l) were
      defined. The limit of detection, lower limit of quantification and upper limit of
      quantification were 0.033, 0.112 and 10 mg/l, respectively. CONCLUSION: This
      method is validated and can be used to study pharmacokinetics of panitumumab or
      to perform therapeutic drug monitoring.

PMID- 29345522
TI  - Goal setting practice in chronic low back pain. What is current practice and is
      it affected by beliefs and attitudes?
AB  - INTRODUCTION: Goal setting, led by the patient, is promising as an effective
      treatment for the management of chronic low back pain (CLBP); however, little is
      known about current practice. The aims of the study were to explore (1) current
      goal setting practice in CLBP among physiotherapists; (2) perceived barriers to
      goal setting in CLBP; and (3) relationship between clinician's attitudes and
      beliefs and goal setting practice. METHOD: A cross-sectional observational
      survey. RESULTS: The majority of respondents used goal setting with the main aim
      of facilitating self-management. The greatest number of goals were set with 50%
      therapist/50% patient involvement. The most common perceived barriers to goal
      setting related to time constraints and lack of skill and confidence. A higher
      biomedical score for treatment orientation of the therapist was associated with a
      lower patient involvement score. CONCLUSION: Goal setting is common practice for
      CLBP and is perceived as a high priority. It is more often a collaboration
      between therapist and patient rather than patient-led with treatment orientation
      of the physiotherapist a predictor of patient involvement. Education of
      healthcare professionals needs to include better understanding of chronic pain to
      orient them away from a biomedical treatment approach, as well as to enhance
      skills in facilitating patient involvement in goal setting.

PMID- 29345524
TI  - Recovery and Performance in Sport: Consensus Statement.
AB  - The relationship between recovery and fatigue and its impact on performance has
      attracted the interest of sport science for many years. An adequate balance
      between stress (training and competition load, other life demands) and recovery
      is essential for athletes to achieve continuous high-level performance. Research
      has focused on the examination of physiological and psychological recovery
      strategies to compensate external and internal training and competition loads. A
      systematic monitoring of recovery and the subsequent implementation of recovery
      routines aims at maximizing performance and preventing negative developments such
      as underrecovery, nonfunctional overreaching, the overtraining syndrome,
      injuries, or illnesses. Due to the inter- and intraindividual variability of
      responses to training, competition, and recovery strategies, a diverse set of
      expertise is required to address the multifaceted phenomena of recovery,
      performance, and their interactions to transfer knowledge from sport science to
      sport practice. For this purpose, a symposium on Recovery and Performance was
      organized at the Technical University Munich Science and Study Center
      Raitenhaslach (Germany) in September 2016. Various international experts from
      many disciplines and research areas gathered to discuss and share their knowledge
      of recovery for performance enhancement in a variety of settings. The results of
      this meeting are outlined in this consensus statement that provides central
      definitions, theoretical frameworks, and practical implications as a synopsis of
      the current knowledge of recovery and performance. While our understanding of the
      complex relationship between recovery and performance has significantly increased
      through research, some important issues for future investigations are also
      elaborated.

PMID- 29345525
TI  - Adsorption of lead ion from aqueous solution by modified walnut shell: kinetics
      and thermodynamics.
AB  - The novel modified walnut shell (WNS-MAH) with higher adsorption capacity for
      lead ion was prepared by reacting walnut shell (WNS) with maleic anhydride. Both
      WNS and WNS-MAH were analyzed by SEM and FTIR. The adsorption capacity of WNS-MAH
      for lead ion was evaluated at different adsorbent doses, pHs, time and
      temperatures. The adsorption kinetics and adsorption isotherms were investigated
      from (298 to 318) K. The adsorption kinetics of lead ion onto WNS-MAH were fitted
      using pseudo-first-order, pseudo-second-order and Elovich models. It was found
      that pseudo-second-order model gives the best correlation results. The diffusion
      mechanism was determined according to the intraparticle diffusion equation and
      Boyd equation. Results suggested the adsorption process was governed by film
      diffusion. The equilibrium adsorption data were fitted with the Freundlich model
      and the Langmuir model. The maximum adsorption capacity of WNS-MAH for lead ion
      removal was 221.24 mg/g at 318 K. The equilibrium adsorption data were analyzed
      using the D-R model, and the feature concentration ([Formula: see text]) was
      determined to distinguish chemisorption and physisorption. The thermodynamic
      parameters (DeltaG, DeltaH and DeltaS) were calculated. Additionally, the
      regeneration property was studied and the adsorption process was confirmed by
      energy disperse spectroscopy.

PMID- 29345523
TI  - Hexim1, an RNA-controlled protein hub.
AB  - Hexim1 acts as a tumor suppressor and is involved in the regulation of innate
      immunity. It was initially described as a non-coding RNA-dependent regulator of
      transcription. Here, we detail how 7SK RNA binds to Hexim1 and turns it into an
      inhibitor of the positive transcription elongation factor (P-TEFb). In addition
      to its action on P-TEFb, it plays a role in a variety of different mechanisms: it
      controls the stability of transcription factor components and assists binding of
      transcription factors to their targets.

PMID- 29345526
TI  - Differential Gait Patterns by History of Falls and Knee Pain Status in Healthy
      Older Adults: Results From the Baltimore Longitudinal Study of Aging.
AB  - Consideration of knee pain can be crucial for identifying fall-related gait
      patterns. While walking, gait parameters at usual speed were examined in persons
      with different falls and knee pain status. A total of 439 adults aged 60-92 years
      participated in this study. Persons with a history of falls had a wider stride
      width (p = .036) and longer double support time (p = .034) than nonfallers. In
      the absence of knee pain, fallers had longer double support time than nonfallers
      (p = .012), but no differences in double support time by history of falls were
      observed in participants with knee pain. With slower gait speed, fallers with
      knee pain have narrower stride width and larger hip range of motion (p = .027 and
      p = .001, respectively). Results suggest the importance of considering knee pain
      in fall studies for better understanding the fall-related differential gait
      mechanisms and for designing fall prevention intervention strategies.

PMID- 29345528
TI  - Linguistic analysis of patients with mood and anxiety disorders during cognitive
      behavioral therapy.
AB  - We analyzed the verbal behavior of patients with mood or/and anxiety disorders
      during psychotherapy. Investigating the words people used, we expected
      differences due to cognitive and emotional foci in patients with depression vs.
      anxiety. Transcripts of therapy sessions from 85 outpatients treated with
      cognitive behavioral therapy were analyzed using the software program Linguistic
      Inquiry and Word Count. Multivariate group comparisons were carried out
      investigating the LIWC-categories first-person-singular pronouns, sad, anxiety
      and fillers. Differences between the three diagnostic groups were found in verbal
      utterances related to sadness (p = .05). No differences were found for first
      person-singular pronouns and content-free fillers. Comparing the distinct groups
      "depression" and "anxiety", depressed patients used more words related to sadness
      (p = .01). Mood and anxiety disorders differ in the experience of emotions, but
      only slightly in self-focused attention. This points to differences in language
      use for different diagnostic groups and may help to improve diagnostic procedures
      or language-driven interventions which enhance therapists' attention to patients'
      verbal behavior.

PMID- 29345527
TI  - Does Problem Focused Coping Buffer the Effects of Trait Anxiety on Depressive
      Symptoms of Chronic Urticaria Patients?
AB  - The present study examined the moderating role of problem-focused coping in trait
      anxiety-depressive symptoms' relationship in patients with chronic urticaria
      (CU). Eighty-eight CU patients, who applied to an outpatient clinic of Clinical
      Immunology and Allergic Diseases, filled out a questionnaire set including State
      Trait Anxiety Inventory, Ways of Coping Inventory, and Beck Depression Inventory.
      The results suggested that CU patients high on trait anxiety reported more
      depressive symptoms, and the ones using more problem-focused coping (PFC)
      strategies reported less depressive symptoms. Also, PFC strategies moderated
      trait anxiety-depressive symptoms relation. Accordingly, PFC strategies did not
      lead to any significant difference in CU patients who were low on trait anxiety
      in terms of the level of depressive symptoms. However, CU patients with high
      trait anxiety experienced significantly less depressive symptoms if they used
      more PFC strategies. The findings were discussed in the light of the relevant
      literature.

PMID- 29345529
TI  - Effects of Telestroke on Thrombolysis Times and Outcomes: A Meta-analysis.
AB  - OBJECTIVE: Telestroke systems are tools, used to provide an advanced stroke care
      in regions without sufficient neurologic services. We performed this meta
      analysis to assess the effects of telemedicine on treatment times and clinical
      outcomes of acute stroke care. METHODS: A literature search of PubMed, SCOPUS,
      and Cochrane CENTRAL was conducted for original studies investigating
      telemedicine applications in acute stroke care. Dichotomous data on treatment
      outcomes were pooled as odds ratios (ORs), while continuous data on thrombolysis
      times were pooled as mean differences (MDs) with 95% confidence interval (CI),
      using RevMan software (version 5.3). RESULTS: Pooling data from 26 studies (6605
      thrombolysed patients) showed no significant differences between the telestroke
      and control groups in terms of in-hospital mortality (OR = 1.21, 95% CI [0.98,
      1.49]), 90-day mortality (OR = 1.08, 95% CI [0.85, 1.37]), symptomatic
      intracranial hemorrhage (sICH) (OR = 1.10, 95% CI [0.79, 1.53]), and favorable
      clinical outcome at discharge (OR = 1.03, 95% CI [0.69, 1.53]) and 90 days later
      (OR = 0.99, 95% CI [0.82, 1.18]). The onset-to-door (OTD) duration (MD = -10.4
      minutes, 95% CI [-14.79, -.01]) and length of hospital stay (MD = -0.55 days, 95%
      CI [-1.02, -0.07]) were significantly shorter in the telestroke group, compared
      to the control group. Although the overall effect estimate (under the fixed
      effect model) showed a significant decrease in the onset-to-treatment (OTT)
      duration in the telestroke group (MD = -5.83 minutes, 95% CI [-8.57, -3.09]),
      employing the random-effects model for between-study heterogeneity abolished this
      significance (MD = -5.90 minutes, 95% CI [-13.23, 1.42]). CONCLUSION: Telestroke
      significantly reduced OTD and hospital stay durations in stroke patients without
      increasing the risk of mortality or sICH. Therefore, telemedicine can improve
      stroke care in regional areas with minor experience in thrombolysis. Further
      randomized controlled trials are needed to assess the benefits of telestroke
      systems, especially in terms of cost-effectiveness and quality of life outcomes.

PMID- 29345530
TI  - Who benefits from psychotherapies for adult depression? A meta-analytic update of
      the evidence.
AB  - It is not clear whether specific target groups for psychotherapies in adult
      depression benefit as much from these treatments as other patients. We examined
      target groups that have been examined in randomized trials, including women,
      older adults, students, minorities, patients with general medical disorders, and
      specific types of depression, and we examined where patients were recruited. We
      conducted subgroup and multivariate metaregression analyses in a sample of 256
      trials (with 332 comparisons) comparing psychotherapy with an inactive control
      condition. Only 22% of the studies had low risk of bias (RoB), heterogeneity was
      high and there was a considerable risk of publication bias. A meta-regression
      analysis among low RoB studies showed that effect sizes found for studies among
      women, older adults, patients with general medical disorders, patients recruited
      from primary care, and patients scoring above a cut-off on a self-rating
      depression scale, did not differ significantly from effect sizes from other
      studies. For other target groups, the number of low RoB studies was too small to
      draw any conclusion. We found few indications that psychotherapies for adult
      depression are more or less effective in women, older adults, patients with
      comorbid general medical disorders, and primary care patients.

PMID- 29345531
TI  - How Tailoring the Mode of Information Presentation Influences Younger and Older
      Adults' Satisfaction with Health Websites.
AB  - Although older adults are increasingly using online health information, many
      websites are not senior-friendly, which might lead to user-problems and
      dissatisfaction among older people. It has been suggested that websites targeted
      at older adults should take into account age-related abilities and limitations,
      for example by providing the opportunity to adjust the modality (i.e., "mode") of
      information presentation based on visual and auditory capabilities. This study
      investigates the effects of a mode-tailored website, allowing users to self
      tailor the mode of information presentation, on younger and older adults'
      satisfaction with health websites. The results from a 5 (condition: tailored vs.
      text, text with visuals, text with audiovisual, combination) * 2 (age: younger
      [25-45] vs. older [>= 65] adults) experimental study (N = 563) show that mode
      tailoring positively influenced satisfaction with the attractiveness and
      comprehensibility of the website, as compared to non-tailored conditions. These
      effects on website satisfaction were not different for younger and older adults.
      The current study provides relevant insights for researchers and practitioners in
      the field of digital health communication.

PMID- 29345532
TI  - Ischemic Preconditioning: No Influence on Maximal Sprint Acceleration
      Performance.
AB  - Ischemic preconditioning (IPC) was initially developed to protect the myocardium
      from ischemia through altered cardiocyte metabolism. Because of the observed
      effects on metabolism and oxygen kinetics, IPC gained interest as a potential
      ergogenic aid in sports. Limited research evaluating the effects of IPC on
      maximal short-duration activities has been performed, and of the existing
      literature, mixed outcomes resulting from intrasubject variation may have clouded
      the efficacy of this technique for enhancing sprint performance. Therefore, the
      current study employed a randomized repeated-measures crossover design with IPC,
      placebo (SHAM), and control conditions while using sprint-trained athletes (N =
      18) to determine the effect of IPC (3 * 5-min occlusions, with 5-min
      reperfusion), concluding 15 min prior to maximal 10-s and 20-m sprinting. A
      visual analog scale was used in conjunction with the sprint trials to evaluate
      any possible placebo effect on performance. Despite a "significantly beneficial"
      perception of the IPC treatment compared with the SHAM trials (P < .001), no
      changes in sprint performance were observed after either the IPC or SHAM
      condition over 10 m (IPC Delta  < 0.01 [0.02] s, SHAM Delta  < 0.01 [0.02] s) or
      20 m (IPC Delta = -0.01 [0.03] s, SHAM Delta < 0.01 [0.03] s) compared with
      control. Thus, an IPC protocol does not improve 10- or 20-m sprint performance in
      sprint-trained athletes.

PMID- 29345533
TI  - Daily Bicycling in Older Adults May be Effective to Reduce Fall Risks-A Case
      Control Study.
AB  - Older adults gain many health benefits from riding bicycles regularly. We aimed
      to explore whether older persons who ride bicycles regularly have better balance
      than controls. Balance control and voluntary stepping were assessed in 20 older
      adults aged 65-85 years who live in an agricultural community village and who
      ride bicycles regularly, and 30 age- and gender-matched nonbicycle riders (NBR).
      Self-reported function and fear of fall were also assessed. Bicycle riders (BR)
      showed significantly better balance, faster voluntary stepping, and better self
      reported advanced lower-extremity function compared with NBR. The results might
      suggest that bicycling regularly preserves balance control and speed of voluntary
      stepping in older adults because bicycling might maintain specific balance
      coordination patterns. The results should be treated with caution as bicycle
      riders were older adults who selected an active lifestyle (i.e., bicycling as
      well as living in an agricultural village) that may bias the results.

PMID- 29345534
TI  - A new stipitate species of Crepidotus from India and Thailand, with notes on
      other tropical species.
AB  - A new Asian species of Crepidotus (Basidiomycota, Agaricales), C. asiaticus, is
      presented based on morphological and nuc rDNA internal transcribed spacer (ITS1
      5.8S-ITS2 = ITS) and large subunit (28S) sequence data. This new species, found
      in India and Thailand, is characterized by the centrally stipitate medium-sized
      basidiomata, orange to reddish brown pileus, white to brownish orange lamellae,
      and white stipe. Based on morphology, C. asiaticus is similar to the neotropical
      C. thermophilus. However, the microscopic characters, especially the size and
      shape of the basidiospores, can be used to distinguish these two taxa, as well as
      their geographic distributions. Further, the phylogenetic position of C.
      asiaticus is unique based on ITS and 28S nuc rDNA sequences. Melanomphalia
      argipoda, described by Singer from Ecuador, is also a stipitate Crepidotus based
      on an ITS sequence of the type specimen, so the new combination is proposed here.
      Phylogenetically, the three species form a monophyletic group with the Asiatic C.
      asiaticus forming the sister lineage to the neotropical C. argipodus and C.
      thermophilus.

PMID- 29345535
TI  - Coping Styles Mediate Perfectionism Associations with Depression Among
      Undergraduate Students.
AB  - To better understand depression among adolescent university students, this study
      was designed to examine coping style as a potential mediator between
      perfectionism and depression. Participants comprised 510 undergraduate students
      from Malaysia. Structural Equation Modelling demonstrated that personal standards
      perfectionism and task-focused coping style were negatively associated with
      depression, while emotion-focused coping style, avoidant coping style, and
      evaluative concerns perfectionism were positively associated with depression.
      Multiple mediator modelling provided evidence that coping styles partially
      mediated the relationship between perfectionism and depression. These findings
      advance current knowledge by suggesting how perfectionism may contribute to
      depression and may inform the development of more effective prevention and
      intervention programs for depression.

PMID- 29345536
TI  - UASB-septic tank as an alternative for decentralized wastewater treatment in
      Mexico.
AB  - The aim of this work was to evaluate the performance of a UASB-septic tank as a
      decentralized treatment of high-strength municipal wastewater under two different
      HRTs (48 and 72 h). Thus, a lab-scale (44.85 L) UASB-septic tank constituted by
      three compartments was operated under HRT 72 and 48 h. Removal efficiencies of
      total chemical oxygen demand (COD), biological oxygen demand (BOD5) and suspended
      solids (SS) ranged from 60% to 80% for the first two parameters and from 70% to
      90% for the last one. According to the statistical analysis, it was established
      that decreasing HRT from 72 to 48 h did not affect the performance of the UASB
      septic tank; therefore, the latter HRT is recommended to be used for operation.
      In the first compartment, most of the organic matter removal was carried out,
      while the other two compartments served as polishing. Over the course of six
      months, the VS concentration and VS/TS ratio in sludge blanket decreased,
      indicating digestion and stabilization of the retained solids. Also, an increase
      of 4% in sludge volume was observed; thus, time for desludging would be
      approximately five years. Comparison of the UASB-septic tank and the UASB reactor
      showed that both systems had similar performance regarding effluent
      concentrations of organic matter and solids. Thus, under low volumetric organic
      load conditions (less than 20 mg COD/L h), the former is an attractive option for
      municipal wastewater treatment.

PMID- 29345537
TI  - Postmatch Perceived Exertion, Feeling, and Wellness in Professional Soccer
      Players.
AB  - PURPOSE: To assess postmatch perceived exertion, feeling, and wellness according
      to the match outcome (winning, drawing, or losing) in professional soccer
      players. METHODS: In total, 12 outfield players were followed during 52 official
      matches where the outcomes (win, draw, or lose) were noted. Following each match,
      players completed both a 10-point Borg scale modified by Foster and an 11-point
      Hardy and Rejeski scale rating of perceived feeling. Rating of perceived sleep
      quality, stress, fatigue, and muscle soreness was collected separately on a 7
      point scale the day following each match. RESULTS: Player rating of perceived
      exertion was higher by a very large magnitude following a loss compared with a
      draw or a win and higher by a small magnitude after a draw compared with a win.
      Players felt more pleasure after a win compared with a draw or loss and more
      displeasure after a loss compared with draw. The players reported a largely and
      moderately better perceived sleep quality, less stress, and fatigue following a
      win compared with a draw or a loss and a moderately bad perceived sleep quality,
      higher stress, and fatigue following a draw compared with a loss. In contrast,
      only a trivial-small change was observed in perceived muscle soreness between all
      outcomes. CONCLUSION: Match outcomes moderately to largely affect rating of
      perceived exertion, feeling, sleep quality, stress, and fatigue, whereas
      perceived muscle soreness remains high regardless of the match outcome. However,
      winning a match decreases the strain and improves both pleasure and wellness in
      professional soccer players.

PMID- 29345538
TI  - Real-time monitoring of nanoscale TiO2 concentration by spectrophotometry:
      implications of agglomeration due to natural organic matter and multivalent ions.
AB  - The study of the environmental fate of nanoscale TiO2 (n-TiO2) is a major recent
      research focus which requires a rapid and accurate on-site concentration
      determination method. Inductively coupled plasma mass spectroscopy (ICP-MS) has
      been the most widely used method for determining the concentration of n-TiO2 in
      environmental samples; however, poses many challenges, such as hazardous
      hydrofluoric acid pre-treatment and clear limitations in mobile on-site
      measurement and monitoring. This study demonstrates that industrial wastewater
      containing natural organic matter (NOM) can present a major challenge to the
      analysis of n-TiO2 by ICP-MS, and introduces a spectrophotometry technique that
      can be used as an alternative. The results suggest that spectrophotometry methods
      can be more accurate than slurry nebulization ICP-MS for measuring the
      concentrations of n-TiO2 in wastewater containing NOM under low salt conditions.
      Furthermore, this study demonstrates the use of a portable flow-through
      spectrophotometer for use in applications of wastewater treatment and
      environmental monitoring with real-time feedback of n-TiO2 concentrations. The
      ability to detect and monitor n-TiO2 will greatly assist in improving the
      understanding of hazards and risks that emerging nanomaterials pose to the
      environment and the public health.

PMID- 29345539
TI  - Working Memory Updating: Load and Binding.
AB  - In the present study, we aimed to examine how specific objects are updated in
      working memory. We compared conditions in which contents or content-context
      bindings from working memory were both encoded and updated (Experiment 1). In
      addition, for bindings, we manipulated the memory load (i.e., number of contents)
      to maintain during updating. Results indicated that memory load did not
      specifically affect the process; rather, the content-context binding (vs. single
      contents) was critical in determining the increase in response latencies. Results
      were replicated even in Experiment 2, in which we manipulated the spatial
      locations of the to-be-recognized probes. Results showed evidence of a potential
      dissociation between updating of memory contents-only and content-context
      bindings. In addition, memory load and spatial coherence between phases and probe
      recognition did not interact with updating performance. Overall, results were
      taken as a contribution toward mapping the complex nature of the updating
      mechanism.

PMID- 29345541
TI  - Running Mechanics and Metabolic Responses With Water Bottles and Bottle Belt
      Holders.
AB  - PURPOSE: To determine whether differential kinematics, kinetics, rates of energy
      use, and cardiopulmonary responses occur during running with water bottles and
      bottle belt holders compared with running only. METHODS: Trained runners (N = 42;
      age 27.2 [6.4] y) ran on an instrumented treadmill for 4 conditions in a
      randomized order: control run (CON), handheld full water bottle (FULL; 16.9 fluid
      oz; 454 g), handheld half-full water bottle (HALF; 8.4 fluid oz; 227 g), and
      waist-worn bottle belt holder (BELT; hydration belt; 676 g). Gas exchange was
      measured using a portable gas analyzer. Kinetic and kinematic responses were
      determined by standard 3-dimensional videographic techniques. Interactions of
      limb side (right and left) by study condition (CON, FULL, HALF, and BELT) were
      tested for rates of oxygen use and energy expenditure and kinematic and kinetic
      parameters. RESULTS: No significant limb-side * condition interactions existed
      for rates of oxygen use or energy expenditure. A significant interaction occurred
      with sagittal elbow flexion (P < .001). Transverse pelvic-rotation excursions
      differed on average 3.8 degrees  across conditions. The minimum sagittal hip
      flexion moment was higher in the right leg in the HALF and BELT conditions
      compared with CON (P < .001). CONCLUSIONS: Carrying water by hand or on the waist
      does not significantly change the kinematics of running motion, rates of oxygen
      use and energy expenditure, or cardiopulmonary measures over short durations.
      Runners likely make adjustments to joint moments and powers that preserve balance
      and protect the lower-extremity joints while maintaining rates of oxygen use and
      energy expenditure.

PMID- 29345542
TI  - Effects of Late-Night Training on "Slow-Wave Sleep Episode" and Hour-by-Hour
      Derived Nocturnal Cardiac Autonomic Activity in Female Soccer Players.
AB  - PURPOSE: To assess the sensitivity of nocturnal heart-rate-variability-monitoring
      methods to the effects of late-night soccer training sessions in female athletes.
      METHODS: Eleven female soccer players competing in the first division of the
      Portuguese soccer league wore heart-rate monitors during sleep at night
      throughout a 1-wk competitive in-season microcycle, after late-night training
      sessions (n = 3) and rest days (n = 3). Heart rate variability was analyzed
      through "slow-wave sleep episode" (10-min duration) and "hour by hour" (all the
      RR intervals recorded throughout the hours of sleep). Training load was
      quantified by session rating of perceived exertion (281.8 [117.9] to 369.0
      [111.7] arbitrary units [a.u.]) and training impulse (77.5 [36.5] to 110.8 [31.6]
      a.u.), added to subjective well-being ratings (Hopper index = 11.6 [4.4] to 12.8
      [3.2] a.u.). These variables were compared between training and rest days using
      repeated-measures analysis of variance. RESULTS: The log-transformed slow-wave
      sleep-episode cardiac autonomic activity (lnRMSSD [natural logarithm of the
      square root of the mean of the sum of the squares of differences between adjacent
      normal RR intervals] varying between 3.92 [0.57] and 4.20 [0.60] ms; [Formula:
      see text]; 95% confidence interval, .01-.26), lnHF (natural logarithm of high
      frequency), lnLF (natural logarithm of low frequency), lnSD1 (natural logarithm
      of short-term beat-to-beat variability), and lnSD2 (natural logarithm of long
      term beat-to-beat variability), and the nontransformed LF/HF were not different
      among night-training session days and rest days (P > .05). Considering the hour
      by-hour method (lnRMSSD varying between 4.05 [0.35] and 4.33 [0.32] ms; [Formula:
      see text]; 95% confidence interval, .26-.52), lnHF, lnLF, lnSD1, and lnSD2 and
      the nontransformed LF/HF were not different among night-training session days and
      rest days (P > .05). CONCLUSION: Late-night soccer training does not seem to
      affect nocturnal slow-wave sleep-episode and hour-by-hour heart-rate-variability
      indices in highly trained athletes.

PMID- 29345540
TI  - Cost-effectiveness analysis of asymptomatic peripheral artery disease screening
      with the ABI test.
AB  - Screening for asymptomatic peripheral artery disease (aPAD) with the ankle
      brachial index (ABI) test is hypothesized to reduce disease progression and
      cardiovascular (CV) events by identifying individuals who may benefit from early
      initiation of medical therapy. Using a Markov model, we evaluated the cost
      effectiveness of initiating medical therapy (e.g. statin and ACE-inhibitor) after
      a positive ankle-brachial index (ABI) screen in 65-year-old patients. We modeled
      progression to symptomatic PAD (sPAD) and CV events with and without ABI
      screening, evaluating differences in costs and quality-adjusted life years
      (QALYs). The cost of the ABI test, physician visit, new medication, CV events,
      and interventions for sPAD were incorporated in the model. We performed
      sensitivity analysis on model variables with uncertainty. Our model found an
      incremental cost of US $338 and an incremental QALY of 0.00380 with one-time ABI
      screening, resulting in an incremental cost-effectiveness ratio (ICER) of
      $88,758/QALY over a 35-year period. The variables with the largest effects in the
      ICER were aPAD disease prevalence, cost of monthly medication after a positive
      screen and 2-year medication adherence rates. Screening high-risk populations,
      such as tobacco users, where the prevalence of PAD may be 2.5 times higher,
      decreases the ICER to $24,092/QALY. Our analysis indicates the cost effectiveness
      of one-time screening for aPAD depends on prevalence, medication costs, and
      adherence to therapies for CV disease risk reduction. Screening in higher-risk
      populations under favorable assumptions about medication adherence results in the
      most favorable cost effectiveness, but limitations in the primary data preclude
      definitive assessment of cost effectiveness.

PMID- 29345543
TI  - Physical Activity and Sitting Time Are Specifically Associated With Multiple
      Chronic Diseases and Medicine Intake in Brazilian Older Adults.
AB  - The purpose of the study was to clarify the independent association between
      sedentary behavior and physical activity with multiple chronic diseases and
      medicine intake in older individuals. Sedentary behavior and physical activity
      were measured by questionnaires. Diseases and medication use were self-reported.
      Poisson's regression was adopted for main analysis, through crude and adjusted
      prevalence ratio and confidence interval of 95%. For men, sedentary time >4
      hr/day presented a 76% higher prevalence of >=2 chronic diseases, while physical
      inactivity increases the likelihood of using >=2 medicines in 95%. For women,
      sedentary behavior >4 hr/day presented an 82% and 43% greater prevalence for >=2
      chronic diseases and the intake of >=2 medicines, respectively. Sedentary
      behavior represents an independent associated factor of multiple chronic diseases
      in older men and women. In addition, inactivity for men and sedentarism for women
      are associated with the amount of medicine intake.

PMID- 29345544
TI  - Editorial.

PMID- 29345545
TI  - Decisive Moment: A Metric to Determine Success in Elite Karate Bouts.
AB  - PURPOSE: To evaluate the concept of decisive moment (DM) as a novel analysis
      approach providing insights into factors leading to successful high-performance
      kumite karate outcomes using time-motion variables. DM represents the moment from
      which 1 of the 2 opponents uninterruptedly dominates the other until the end of
      the fight. METHODS: A total of 120 elite seniors (60 men and 60 women) World
      Karate Federation combats were analyzed during 2 World Championships (2012 and
      2014). Specific characteristics of karate combat (strategy, technique, tactic,
      target, and effectiveness) were evaluated and classified in 3 sections: at,
      before, and after DM. RESULTS: DM occurred at about 49% (32.8%) of bout duration.
      Up to DM no clearly identifiable differences in performance characteristics were
      found between winners and losers. At and after DM, an offensive strategy with
      focus on upper-limb techniques, attack and counterattack, targeting the head
      showed highest potential to achieve and maintain dominance and to win. After DM,
      losers showed increasingly reactive techniques, mainly timed attacks and
      combinatory techniques. CONCLUSION: The DM concept presents a novel approach to
      time-motion analysis, which for the first time allowed identification of clear
      discriminating factors of success and defeat in kumite karate at the highest
      performance level.

PMID- 29345546
TI  - Enhanced biosorption of transition metals by living Chlorella vulgaris
      immobilized in Ca-alginate beads.
AB  - In this study freely suspended and Ca-alginate immobilized C. vulgaris cells were
      used for the biosorption of Fe(II), Mn(II), and Zn(II) ions, from the aqueous
      solution. Experimental data showed that biosorption capacity of algal cells was
      strongly dependent on the operational condition such as pH, initial metal ions
      concentration, dosages, contact time and temperature. The maximum biosorption of
      Fe(II) 43.43, Mn(II) 40.98 and Zn(II) 37.43 mg/g was achieved with Ca-alginate
      immobilized algal cells at optimum pH of 6.0, algal cells dosage 0.6 g/L, and
      contact time of 450 min at room temperature. The biosorption efficiency of freely
      suspended and immobilized C. vulgaris cells for heavy metals removal from the
      industrial wastewater was validated. Modeling of biosorption kinetics showed good
      agreements with pseudo-second-order. Langmuir and D-R isotherm models exhibited
      the best fit of experimental data. The thermodynamic parameters (DeltaG degrees ,
      DeltaH degrees , and DeltaS degrees ) revealed that the biosorption of considered
      metal ions was feasible, spontaneous and exothermic at 25-45 degrees C. The SEM
      showed porous morphology which greatly helps in the biosorption of heavy metals.
      The Fourier transform infrared spectrophotometer (FTIR) and X-rays Photon
      Spectroscopy (XPS) data spectra indicated that the functional groups
      predominately involved in the biosorption were C-N, -OH, COO-, -CH, C=C, C=S and 
      C-. These results shows that immobilized algal cells in alginate beads could
      potentially enhance the biosorption of considered metal ions than freely
      suspended cells. Furthermore, the biosorbent has significantly removed heavy
      metals from industrial wastewater at the optimized condition.

PMID- 29345547
TI  - Are Current Physical Match Performance Metrics in Elite Soccer Fit for Purpose or
      Is the Adoption of an Integrated Approach Needed?
AB  - Time-motion analysis is a valuable data-collection technique used to quantify the
      physical match performance of elite soccer players. For over 40 years,
      researchers have adopted a "traditional" approach when evaluating match demands
      by simply reporting the distance covered or time spent along a motion continuum
      of walking through to sprinting. This methodology quantifies physical metrics in
      isolation without integrating other factors, and this ultimately leads to a 1
      dimensional insight into match performance. Thus, this commentary proposes a
      novel "integrated" approach that focuses on a sensitive physical metric such as
      high-intensity running but contextualizes this in relation to key tactical
      activities for each position and collectively for the team. In the example
      presented, the integrated model clearly unveils the unique high-intensity profile
      that exists due to distinct tactical roles, rather than 1-dimensional "blind"
      distances produced by traditional models. Intuitively, this innovative concept
      may aid coaches' understanding of the physical performance in relation to the
      tactical roles and instructions given to the players. In addition, it will enable
      practitioners to effectively translate match metrics into training and testing
      protocols. This innovative model may well aid advances in other team sports that
      incorporate similar intermittent movements with tactical purpose. Evidence of the
      merits and application of this new concept is needed before the scientific
      community accepts this model as it may well add complexity to an area that
      conceivably needs simplicity.

PMID- 29345548
TI  - ABI: The goal line is in sight.

PMID- 29345549
TI  - Veterinary Medical Students' Motivations for Exercise.
AB  - The Centers for Disease Control (CDC) declares exercise to be one of the most
      important activities one can do to improve health. The benefits of exercise are
      well documented and include both physiologic and psychological health. Given the
      current landscape of wellness issues in veterinary medical education, it is
      necessary that students engage in exercise activities to manage stress and
      increase overall health. Therefore, to develop targeted interventions with the
      greatest likelihood for success, it is first necessary to understand what
      motivates veterinary medical students to exercise given their unique situational
      and environmental factors. This study is the first to explore this issue
      systematically in veterinary medical education, thus it is the authors' hope that
      the findings from this research will help identify exercise-related wellness
      interventions that could be implemented in veterinary medical schools.

PMID- 29345550
TI  - An Anatomy Pre-Course Predicts Student Performance in a Professional Veterinary
      Anatomy Curriculum.
AB  - Little to no correlation has been identified between previous related
      undergraduate coursework or outcomes on standardized tests and performance in a
      veterinary curriculum, including anatomy coursework. Therefore, a relatively
      simplistic method to predict student performance before entrance would be
      advantageous to many. The purpose of this study was to evaluate whether there is
      a correlation between performance in a veterinary anatomy pre-course and
      subsequent performance within a professional anatomy curriculum. Incoming first
      year veterinary students at the Louisiana State University School of Veterinary
      Medicine were asked to participate in a free weeklong pre-course, before the
      start of the semester. The pre-course covered the musculoskeletal anatomy of the
      canine thoracic limb using dissection-based methods. Student performance, as
      evaluated by test grades in the pre-course, did indeed correlate with test grades
      in professional veterinary anatomy courses. A significant and positive
      correlation was identified between pre-course final exam performance and
      performance on examinations in each of 3 professional anatomy courses.
      Qualitative analyses of student comments pertaining to their experience within
      the pre-course indicated differences in the perceived benefits of the pre-course
      between high-, middle-, and low-performing students. These varied perceptions may
      provide predictive feedback as well as guidance for supporting lower performing
      students. Together, these results indicate that performance in a weeklong pre
      course covering only a small portion of canine anatomy is a strong predictor of
      performance within a professional anatomy curriculum. In addition, the pre-course
      differentially affected student perceptions of their learning experience.

PMID- 29345551
TI  - Quantifying Novice and Expert Differences in Visual Diagnostic Reasoning in
      Veterinary Pathology Using Eye-Tracking Technology.
AB  - Visual diagnostic reasoning is the cognitive process by which pathologists reach
      a diagnosis based on visual stimuli (cytologic, histopathologic, or gross
      imagery). Currently, there is little to no literature examining visual reasoning
      in veterinary pathology. The objective of the study was to use eye tracking to
      establish baseline quantitative and qualitative differences between the visual
      reasoning processes of novice and expert veterinary pathologists viewing cytology
      specimens. Novice and expert participants were each shown 10 cytology images and
      asked to formulate a diagnosis while wearing eye-tracking equipment (10 slides)
      and while concurrently verbalizing their thought processes using the think-aloud
      protocol (5 slides). Compared to novices, experts demonstrated significantly
      higher diagnostic accuracy (p <.017), shorter time to diagnosis (p <.017), and a
      higher percentage of time spent viewing areas of diagnostic interest (p <.017).
      Experts elicited more key diagnostic features in the think-aloud protocol and had
      more efficient patterns of eye movement. These findings suggest that experts'
      fast time to diagnosis, efficient eye-movement patterns, and preference for
      viewing areas of interest supports system 1 (pattern-recognition) reasoning and
      script-inductive knowledge structures with system 2 (analytic) reasoning to
      verify their diagnosis.

PMID- 29345552
TI  - The Effect of Preceding Race Efforts on Pacing and Short-Track Speed Skating
      Performance.
AB  - PURPOSE: To examine whether preceding high-intensity race efforts in a
      competitive weekend affect pacing behavior and performance in elite short-track
      speed skaters. METHODS: Finishing and intermediate lap times were gathered from
      500-, 1000-, and 1500-m short-track speed skating world cups during the seasons
      2011-2016. The effect of preceding races on pacing behavior and performance was
      explored using 2 studies. Study I: The effect of competing in extra races due to
      the repechage (Rep) system, leading to an increased number of high-intensity race
      efforts prior to the subsequent main tournament race, was explored (500-m, n =
      32; 1000-m, n = 34; and 1500-m, n = 47). Study II: The performance of skaters
      over the tournament days was evaluated (500-m, n = 129; 1000-m, n = 54; and 1500
      m, n = 114). For both analytic approaches, a 2-way repeated-measures analysis of
      variance was used to assess differences in pacing and performance within skaters
      over the races. RESULTS: An additional number of preceding high-intensity race
      efforts due to the Rep system reduced the qualification percentage in the first
      main tournament race for the next stage of competition in all events (500-m,
      direct qualification = 57.3%, Rep = 25.0%; 1000-m, direct = 44.2%, Rep = 28.3%;
      and 1500-m, direct = 27.1%, Rep = 18.2%) and led to a decreased pace in the
      initial 2 laps of the 500-m event. By contrast, tournament day (Saturday vs
      Sunday) only affected the pacing behavior of female skaters during the 1500-m
      event. CONCLUSION: High-intensity race efforts earlier in the day affected pacing
      and performance of elite skaters, whereas the effect of high-intensity race
      efforts from the previous day seemed to be only marginal.

PMID- 29345553
TI  - Quality and Variability of Patient Directions in Electronic Prescriptions in the
      Ambulatory Care Setting.
AB  - BACKGROUND: The prescriber's directions to the patient (Sig) are one of the most
      quality-sensitive components of a prescription order. Owing to their free-text
      format, the Sig data that are transmitted in electronic prescriptions (e
      prescriptions) have the potential to produce interpretation challenges at
      receiving pharmacies that may threaten patient safety and also negatively affect
      medication labeling and patient counseling. Ensuring that all data transmitted in
      the e-prescription are complete and unambiguous is essential for minimizing
      disruptions in workflow at prescribers' offices and receiving pharmacies and
      optimizing the safety and effectiveness of patient care. OBJECTIVES: To (a)
      assess the quality and variability of free-text Sig strings in ambulatory e
      prescriptions and (b) propose best-practice recommendations to improve the use of
      this quality-sensitive field. METHODS: A retrospective qualitative analysis was
      performed on a nationally representative sample of 25,000 e-prescriptions issued
      by 22,152 community-based prescribers across the United States using 501
      electronic health records (EHRs) or e-prescribing software applications. The
      content of Sig text strings in e-prescriptions was classified according to a Sig
      classification scheme developed with guidance from an expert advisory panel. The
      Sig text strings were also analyzed for quality-related events (QREs). For
      purposes of this analysis, QREs were defined as Sig text content that could
      impair accurate and unambiguous interpretation by staff at receiving pharmacies.
      RESULTS: A total of 3,797 unique Sig concepts were identified in the 25,000 Sig
      text strings analyzed; more than 50% of all Sigs could be categorized into 25
      unique Sig concepts. Even Sig strings that expressed apparently simple and
      straightforward concepts displayed substantial variability; for example, the
      sample contained 832 permutations of words and phrases used to convey the Sig
      concept of "Take 1 tablet by mouth once daily." Approximately 10% of Sigs
      contained QREs that could pose patient safety risks or workflow disruptions that
      could necessitate pharmacist callbacks to prescribers for clarification or other
      manual interventions. CONCLUSIONS: The quality of free-text patient directions in
      e-prescriptions can vary dramatically. However, more than half of all patient
      directions sent in the ambulatory setting can be categorized into only 25 Sig
      concepts. This suggests an immediate, practical opportunity to improve patient
      safety and workflow efficiency for both prescribers and pharmacies.
      Recommendations include implementing enhancements to Sig creation tools in e
      prescribing and EHR software applications, adoption of the Structured and
      Codified Sig format supported by the current national e-prescribing standard, and
      improved usability testing and end-user training for generating complete and
      unambiguous patient directions. Such quality improvements are essential for
      optimizing the safety and effectiveness of patient care as well as for minimizing
      workflow disruptions to both prescribers and pharmacies. DISCLOSURES: This
      research received no specific grant from any funding agency in the public,
      commercial, or not-for-profit sectors. Yang, Ward-Charlerie, Dhavle, and Green
      are employed by Surescripts. Rupp reported receiving consulting fees from
      Surescripts during the conduct of this study. No other disclosures were reported.
      The content in this article is solely the responsibility of the authors and does
      not necessarily represent the official views of Surescripts and Midwestern
      University or any of the affiliated institutions of the authors. Study concept
      and design were contributed by all the authors. Yang and Ward-Charlerie collected
      the data, and data interpretion was performed by Yang, Ward-Charlerie and Dhavle.
      The manuscript was primarily written by Yang, along with Dhavle and Green, and
      revised by Yang, Dhavle, Rupp, and Green.

PMID- 29345554
TI  - Letter to the editor concerning the article "Relationship between school rhythm
      and physical activity in adolescents: the HELENA study" by Vanhelst et al.
      (2017).
AB  - Recently Vanhelst et al. published a study on the relationship between school
      rhythm and physical activity patterns in European adolescents in the Journal of
      Sports Sciences. With this Letter to the Editor we would like to comment on the
      practical implementation and further perspectives of the study.

PMID- 29345555
TI  - The Preparation Period in Basketball: Training Load and Neuromuscular
      Adaptations.
AB  - PURPOSE: To investigate the effect of the preparation period on neuromuscular
      characteristics of 12 professional (PRO) and 16 semiprofessional (SEMIPRO)
      basketball players and relationships between training-load indices and changes in
      neuromuscular physical performance. METHODS: Before and after the preparation
      period, players underwent a countermovement jump (CMJ) test followed by a
      repeated change-of-direction (COD) test consisting of 4 levels with increasing
      intensities. The peripheral neuromuscular functions of the knee extensors (peak
      torque [PT]) were measured using electrical stimulations after each level (PT1,
      PT2, PT3, and PT4). Furthermore, PT Max (the highest value of PT) and PT Dec (PT
      decrement from PT Max to PT4) were calculated. RESULTS: Trivial to small (effect
      size [ES] = -0.17 to 0.46) improvements were found in CMJ variables, regardless
      of competitive level. After the preparation period, peripheral fatigue induced by
      a COD test was similarly reduced in both PRO (PT Dec: from 27.8% [21.3%] to 11.4%
      [13.7%]; ES = -0.71; 90% confidence interval [CI], +/-0.30) and SEMIPRO (PT Dec:
      from 26.1% [21.9%] to 10.2% [8.2%]; ES = -0.69; 90% CI, +/-0.32). Moderate to
      large relationships were found between session rating of perceived exertion
      training load and changes in peak power output (PPO) measured during the CMJs (rs
      [90% confidence interval]: PPOabs, -.46 [+/-.26]; PPOrel, -.53 [+/-.23]) and in
      some PTs measured during the COD test (PT1, -.45 [+/-.26]; PT2, -.44 [+/-.26];
      PT3, -.40 [+/-.27]; and PT Max, -.38 [+/-.28]). CONCLUSIONS: The preparation
      period induced minimal changes in the CMJ, while the ability to sustain repeated
      COD efforts was improved. Reaching high session rating of perceived exertion
      training loads might partially and negatively affect the ability to produce
      strength and power.

PMID- 29345556
TI  - Positional Differences in Elite Basketball: Selecting Appropriate Training-Load
      Measures.
AB  - PURPOSE: To study the structure of interrelationships among external-training
      load measures and how these vary among different positions in elite basketball.
      METHODS: Eight external variables of jumping (JUMP), acceleration (ACC),
      deceleration (DEC), and change of direction (COD) and 2 internal-load variables
      (rating of perceived exertion [RPE] and session RPE) were collected from 13
      professional players with 300 session records. Three playing positions were
      considered: guards (n = 4), forwards (n = 4), and centers (n = 5). High and total
      external variables (hJUMP and tJUMP, hACC and tACC, hDEC and tDEC, and hCOD and
      tCOD) were used for the principal-component analysis. Extraction criteria were
      set at an eigenvalue of greater than 1. Varimax rotation mode was used to extract
      multiple principal components. RESULTS: The analysis showed that all positions
      had 2 or 3 principal components (explaining almost all of the variance), but the
      configuration of each factor was different: tACC, tDEC, tCOD, and hJUMP for
      centers; hACC, tACC, tCOD, and hJUMP for guards; and tACC, hDEC, tDEC, hCOD, and
      tCOD for forwards are specifically demanded in training sessions, and therefore
      these variables must be prioritized in load monitoring. Furthermore, for all
      playing positions, RPE and session RPE have high correlation with the total
      amount of ACC, DEC, and COD. This would suggest that although players perform the
      same training tasks, the demands of each position can vary. CONCLUSION: A
      particular combination of external-load measures is required to describe the
      training load of each playing position, especially to better understand internal
      responses among players.

PMID- 29345557
TI  - Co-registration of cone beam CT and preoperative MRI for improved accuracy of
      electrode localization following cochlear implantation.
AB  - OBJECTIVES: To investigate the clinical usefulness and practicality of co
      registration of Cone Beam CT (CBCT) with preoperative Magnetic Resonance Imaging
      (MRI) for intracochlear localization of electrodes after cochlear implantation.
      METHODS: Images of 20 adult patients who underwent CBCT after implantation were
      co-registered with preoperative MRI scans. Time taken for co-registration was
      recorded. The images were analysed by clinicians of varying levels of expertise
      to determine electrode position and ease of interpretation. RESULTS: After a
      short learning curve, the average co-registration time was 10.78 minutes (StdDev
      2.37). All clinicians found the co-registered images easier to interpret than
      CBCT alone. The mean concordance of CBCT vs. co-registered image analysis between
      consultant otologists was 60% (17-100%) and 86% (60-100%), respectively. The
      sensitivity and specificity for CBCT to identify Scala Vestibuli insertion or
      translocation was 100 and 75%, respectively. The negative predictive value was
      100%. DISCUSSION: CBCT should be performed following adult cochlear implantation
      for audit and quality control of surgical technique. If SV insertion or
      translocation is suspected, co-registration with preoperative MRI should be
      performed to enable easier analysis. There will be a learning curve for this
      process in terms of both the co-registration and the interpretation of images by
      clinicians.

PMID- 29345558
TI  - Activation of NADPH Oxidase by beta-Glucan from Phellinus baumii (Agaricomycetes)
      in RAW 264.7 Cells.
AB  - Production of oxygen-derived free radicals in phagocytes is important in
      preventing bacterial and fungal infections. Among free radicals, superoxide
      anions are a typical reactive oxygen species secreted by macrophages and
      neutrophils. NADPH oxidase (NOX) is a key producer of superoxide anions in these
      cells. beta-glucans from mushrooms modulate the immune system by binding with the
      dectin-1 receptor on macrophages. Dectin-1 functions as a pattern recognition
      receptor that recognizes the pathogen-associated molecular pattern of beta
      glucans. During dectin-1 signaling, NOX functions in the activated macrophages to
      produce ROS, which are critical in antimicrobial host defense. In this study, NOX
      activation was measured using a lucigenin chemiluminescence assay in RAW 264.7
      murine macrophages treated for 1 hour with a beta-glucan fraction from Phellinus
      baumii (BGF; 10, 100, 500, and 1000 MUg/mL) in the absence or presence of phorbol
      12-myristate 13-acetate (PMA) or lipopolysaccharide (LPS). NOX was activated at
      BGF concentrations exceeding 10 MUg/mL. BGF in the presence of PMA or LPS
      activated the enzyme more than treatment with PMA or LPS alone. In the presence
      of the NOX inhibitor diphenyleneiodonium, BGF still activated NOX. When
      macrophages were treated with BGF and Staphylococcus aureus, bacterial viability
      was reduced in a concentration-dependent manner, possibly as a result of
      increased phagocytosis and oxygen radical production by the activated NOX. These
      results demonstrate that BGF is a potent stimulator of NOX in macrophages and
      augments macrophage-mediated phagocytosis and NOX activity.

PMID- 29345559
TI  - Antioxidant and Genotoxic Properties of Hispidin Isolated from the Velvet-Top
      Mushroom, Phaeolus schweinitzii (Agaricomycetes).
AB  - Antioxidant and genotoxic properties of hispidin isolated from the Phaeolus
      schweinitzii mushroom were evaluated with various assays. Hispidin demonstrated
      strong free radical scavenging, oxygen radical absorbance capacity, and ferric
      reducing antioxidant power; in all applied assays, hispidin exhibited antioxidant
      capacity similar to or higher than that of the reference antioxidant Trolox.
      Genotoxic activity of hispidin was assessed using different end points:
      chromosome aberrations, micronuclei, sister chromatid exchanges, and primary DNA
      damage (detected by the comet assay) in human lymphocytes in vitro, and gene
      mutations in the Salmonella/microsome test. Hispidin did not increase the
      frequency of chromosome aberrations, micronuclei, or primary DNA damage in human
      lymphocytes in vitro and did not produce reverse mutation in bacterial cells.
      However, we identified in human lymphocytes a statistically significant dose
      dependent increase in sister chromatid exchange frequency and a decrease in
      replication index and nuclear division index values.

PMID- 29345560
TI  - Shiitake Culinary-Medicinal Mushroom, Lentinus edodes (Agaricomycetes): A Species
      with Antioxidant, Immunomodulatory, and Hepatoprotective Activities in
      Hypercholesterolemic Rats.
AB  - Lentinus edodes is a culinary-medicinal mushroom that has an established history
      of use in Asian therapies. The mushroom offers well-documented beneficial health
      effects such as antihypercholesterolemic, antitumor, and antibacterial
      activities. In this study, dried powder of L. edodes fruiting bodies was used to
      evaluate immunomodulatory, hepatoprotective, and antioxidant effects in
      hypercholesterolemic rats. Albino rats (n = 24) were divided into 3 groups: the
      control (CON) group, the hypercholesterolemia-only group (HCG), and the L. edodes
      group (LEG). Hypercholesterolemia was induced in rats in the HCG and LEG by
      feeding cholesterol and cholic acid in a chow maintenance diet (CMD) for 24 days.
      The CON group was fed the CMD throughout the experiment. The HCG continued on the
      high-cholesterol diet without any L. edodes supplement. The LEG was fed the high
      cholesterol diet supplemented with L. edodes for an additional 42 days. Various
      biological health biomarkers, such as total antioxidant capacity, total oxidant
      status, arylesterase, paraoxonase activity, and liver enzymes in serum were
      studied to evaluate antioxidant and hepatoprotective responses. Cell-mediated
      immunity was evaluated in each group through a delayed type of hypersensitivity
      reaction. The total oxidant status decreased significantly (P <= 0.05) after
      administration of L. edodes in the diet. The cell-mediated immune response
      significantly increased (P <= 0.05) in the LEG. The significant decrease in liver
      enzymes supports the hepatoprotective effect of L. edodes. In conclusion, the
      results show the immunomodulatory, hepatoprotective, and antioxidant activities
      of L. edodes supplementation in hypercholesterolemic rats.

PMID- 29345561
TI  - Characterization of the Effects of the Shiitake Culinary-Medicinal Mushroom,
      Lentinus edodes (Agaricomycetes), on Severe Gestational Diabetes Mellitus in
      Rats.
AB  - This study evaluated the protective effect of Lentinus edodes in rats with
      streptozotocin-induced gestational diabetes mellitus (STZ-GDM) when administered
      orally. The rats received from the 1st to the 19th day of gestation daily doses
      of 100 or 200 mg/kg of lyophilized and reconstituted L. edodes; the animals in
      the saline control group and diabetic control group received a saline solution
      (DS). Gestational diabetes mellitus was induced by streptozotocin (80 mg/kg,
      administered intraperitoneally) on the fourth day of pregnancy; blood glucose >
      180 mg/dL was considered to indicate STZ-GDM. L. edodes reduced catalase in
      plasma. We also observed reduced glucose in plasma, urea, triglycerides, and
      aspartate aminotransferase. There was a decrease in preimplantation loss when
      compared with the DS group. The doses of L. edodes used here had a protective
      effect on the preimplantation parameters in STZGDM. However, the mushroom was not
      able to reverse the deleterious effects caused by streptozotocin throughout the
      evolution of pregnancy.

PMID- 29345562
TI  - Ethanolic Extract of the Golden Oyster Mushroom, Pleurotus citrinopileatus
      (Agaricomycetes), Alleviates Metabolic Syndrome in Diet-Induced Obese Mice.
AB  - Pleurotus citrinopileatus is an edible medicinal mushroom rich in biomolecules
      and thus has a high potential for use in formulating pharmaceutical and
      nutraceutical products. To test its effect on body weight and glucose control, we
      generated diet-induced obese (DIO) C57BL/6J male mice by feeding the mice a high
      fat diet (60% fat) for 8 weeks and treating them with an ethanolic P.
      citrinopileatus extract (PCE) at either 200 or 500 mg/kg body weight for 12
      additional weeks. The results showed that PCE significantly inhibited high-fat
      diet-induced weight gain, fat accumulation, and glucose intolerance in the DIO
      mice. Moreover, the PCE had a beneficial effect on liver and kidney function. On
      the basis of these results, we conclude that PCE is effective in the treatment of
      metabolic syndrome and thus could be a good candidate for use in future
      pharmaceutical or nutraceutical applications.

PMID- 29345563
TI  - Lingzhi or Reishi Medicinal Mushroom, Ganoderma lucidum (Agaricomycetes), as a
      Cardioprotectant in an Oxygen-Deficient Environment.
AB  - Imbalanced oxygen availability is detrimental to normal cell function. Oxygen
      sensitive cells such as cardiomyoblasts experience severe irreversible
      pathophysiological damage under conditions of reduced oxygen availability, such
      as hypoxia. A number of natural therapeutic agents have been explored for their
      potential cytoprotective effects, of which medicinal mushrooms are an important
      source. Ganoderma lucidum, commonly known as lingzhi, is one such mushroom that
      has been elaborately studied for its potential pharmacological properties. In
      this study, aqueous and alcoholic extracts of a natural Himalayan variety of G.
      lucidum were evaluated for their efficiency as remedial agents in treating
      hypoxic injury to H9c2 cardiomyoblasts. The alcoholic extract of G. lucidum
      effectively restored cellular viability at a concentration of 600 MUg/mL and
      aided in maintaining cellular redox balance under hypoxia. Substantial reduction
      in caspase-3 and -7 activation was observed with fluorescent-activated cell
      sorting. Alcoholic extract of G. lucidum minimized oxidative stress as indicated
      by measuring reactive oxygen species, lipid peroxidation, and reduced glutathione
      to-oxidized glutathione ratio, and also by determining changes in hypoxia
      inducible factor 1alpha and associated genes. To ascertain these positive
      outcomes of administration of G. lucidum extracts, certain phytoconstituents
      (nucleobases and flavonoids) were identified using high-performance thin-layer
      chromatography; antioxidant potential was also evaluated. Results indicated that
      both extracts contained notable quantities of nucleobases and flavonoids. The
      extracts also effected high free radical scavenging activities.

PMID- 29345564
TI  - Profiles of Little-Known Medicinal Polypores: Earliella scabrosa
      (Agaricomycetes).
AB  - The purpose of this study was to comprehensively characterize a little-known
      polypore that has recently been found to possess anticancer activity and thus can
      also be used in targeted cancer therapy. Earliella scabrosa is a polypore with
      pantropical distribution and can be found in rainforests in both the Eastern and
      Western Hemispheres. Some reports have described its antioxidant properties and
      free radical scavenging ability. Moreover, isocoumarin, which has been
      successfully used in targeted cancer therapy, was found in extracts of this
      fungus. We recommend further research of E. scabrosa so that more details of its
      health benefits could be used in mycotherapy.

PMID- 29345565
TI  - Identification of Reference Genes and Analysis of Heat Shock Protein Gene
      Expression in Lingzhi or Reishi Medicinal Mushroom, Ganoderma lucidum, after
      Exposure to Heat Stress.
AB  - Ganoderma lucidum has been considered an emerging model species for studying how
      environmental factors regulate the growth, development, and secondary metabolism
      of Basidiomycetes. Heat stress, which is one of the most important environmental
      abiotic stresses, seriously affects the growth, development, and yield of
      microorganisms. Understanding the response to heat stress has gradually become a
      hotspot in microorganism research. But suitable reference genes for expression
      analysis under heat stress have not been reported in G. lucidum. In this study,
      we systematically identified 11 candidate reference genes that were measured
      using reverse transcriptase quantitative polymerase chain reaction, and the gene
      expression stability was analyzed under heat stress conditions using geNorm and
      NormFinder. The results show that 5 reference genes-CYP and TIF, followed by
      UCE2, ACTIN, and UBQ1-are the most stable genes under our experimental
      conditions. Moreover, the relative expression levels of 3 heat stress response
      genes (hsp17.4, hsp70, and hsp90) were analyzed under heat stress conditions with
      different normalization strategies. The results show that use of a gene with
      unstable expression (SAND) as the reference gene leads to biased data and
      misinterpretations of the target gene expression level under heat stress.

PMID- 29345566
TI  - Productivity, Physicochemical Changes, and Antioxidant Activity of Shiitake
      Culinary-Medicinal Mushroom Lentinus edodes (Agaricomycetes) Cultivated on
      Lignocellulosic Residues.
AB  - The effects of substrate and strain on productivity, physicochemical
      characteristics, and compounds with antioxidant activity were evaluated in
      basidiomes of the shiitake mushroom, Lentinus edodes. Strains IE-245 and IE-256
      and the substrates oak wood shavings (OW), sorghum stubble (SS), and sugar cane
      bagasse (SC) were used. Productivity was evaluated by measuring biological
      efficiency (BE), production rate (PR), and yield. Total sugars, total soluble
      solids, pH, titratable acidity, color parameters, total phenolics, flavonoids,
      ascorbic acid, and antioxidant activity of the basidiomes were measured. BE, PR
      and yield were higher with the combination IE-256/SS, at 103.71%, 1.32%, and
      34.57%, respectively. The largest amount of total sugars (17.61 mg glucose . g-1
      dry weight) was found with combination IE-256/SS. Variation was observed in
      basidiome color; the lowest luminosity (L*) value (darkest color) was found in
      the IE-256 strain on the OW substrate (L* = 30.45), whereas that of the IE-245
      strain on the SC substrate was the lightest in color (L* = 57.00). The largest
      amounts of total phenolics were recorded in the IE-256 strain on the OW (6.50 mg
      gallic acid equivalents [GAE] . g-1 dry weight) and the SS substrates (5.85 mg
      GAE . g-1 dry weight). The best antioxidant activity was obtained with IE-256
      0.80, 0.65, and 0.59 MUmol Trolox equivalents . g dry weight-1-on the OW, SC, and
      SS substrates, respectively. Based on the values of BE, PR, and yield, IE-256/SS
      was the most productive. Substrate and strain, and their interactions, influenced
      the physicochemical characteristics of the basidiomes and the amounts of
      compounds with antioxidant activity they contained.

PMID- 29345567
TI  - Proteomic Analysis of Vernalization Responsive Proteins in Winter Wheat Jing841.
AB  - BACKGROUND: Vernalization is one of the pivotal ways for plants to flower. The
      twodimensional gel electrophoresis (2-DE) and matrix-assisted laser
      desorption/ionization time-offlight/ time-of-flight mass spectrometry (MALDI
      TOF/TOF MS) were applied to analyze the changes in protein expression profiles in
      responding to vernalization in leaves of wheat seedling before (0d) and after
      (30d) of vernalization. OBJECTIVE: The main objective of this study was to
      analyze the vernalization-responsive proteins in winter wheat after
      vernalization. METHODS: Winter wheat seedling leaf proteins were extracted by
      phenol extraction coupled with ammonium acetate in methanol. 2-DE was conducted
      according to procedures described in the manual given by the GE manufacture. The
      selected protein spots were identified by MALDITOF/ TOF MS. Gene ontology (GO)
      classification was applied to classify the functions of the differentially
      expressed proteins. Pathway enrichment analysis identified significantly enriched
      metabolic pathways or signal transduction pathways relative to the whole proteins
      background. RESULTS: The results of 2-DE and MALDI-TOF/TOF MS showed that among
      the 65 differentially expressed proteins that were successfully identified under
      vernalization, 30 were up-regulated whereas 35 were down-regulated after
      vernalization, respectively. These vernalization-responsive proteins were found
      to play roles in carbohydrate metabolism, protein metabolism, photosynthesis,
      defense and stress-resistance and may therefore participate in many biological
      processes in responding to vernalization. The enhanced accumulation of proteins
      after vernalization, such as thiamine thiazole synthase, late embryogenesis
      abundant protein, and glutathione-S-transferase, probably play vital roles in the
      mechanisms underlying vernalization response in wheat. CONCLUSION: Our results
      indicated these vernalization-responsive proteins were found to be involved in
      protein metabolism, carbohydrate metabolism, photosynthesis, and stress
      resistance/ defense. The responses of plants to low temperature were very
      complex, involving in a wide range of cellular pathways for signal transduction,
      gene regulation, protein modifications, and metabolic regulation. Studying on
      wheat proteomic profiles in response to vernalization can improve our
      understanding the molecular mechanisms underlying vernalization in cereals. The
      results obtained in this study have provided a novel insight into the mechanisms
      underlying vernalization in cereal crops.

PMID- 29345568
TI  - Surface-bioengineered Gold Nanoparticles for Biomedical Applications.
AB  - The conjugation of gold nanoparticles (AuNPs) with biomolecules could create many
      outstanding biofunctions for the surface-functionalized nanoparticles and extend
      their biomedical applications. In this review, we summarize the recent advances
      in the surface bioengineering of AuNPs with biomolecules, such as DNA, proteins,
      peptides, and biopolymers, in which the details on the structure, functions, and
      properties of surface- bioengineered AuNPs are discussed. In addition, the
      surface-biofunctionalization of AuNPs for biomedical applications like
      biosensing, bioimaging, drug delivery, and tissue engineering are introduced. It
      is expected that this work will be very helpful for readers to understand the
      surface functionalization and engineering techniques for various metallic
      nanoparticles and design novel biomaterials for biomedical applications.

PMID- 29345569
TI  - A Complex Scenario and Underestimated Challenge: The Tumor Microenvironment, ER
      Stress, and Cancer Treatment.
AB  - The paradoxical role of ER stress in malignant diseases is only just being
      unraveled and remains incompletely understood. A particular challenge is the
      complex interplay between spaciotemporal and locoregional microenvironmental
      constraints in solid tumors and stress responses upon treatment; thus, the
      potential for new combinatorial therapeutic options to foster the coincidence of
      ER stress-related deadly events is likely to be underestimated. Without claiming
      this review to be complete, we present a comprehensive overview of the signaling
      mechanisms associated with the unfolded protein response (UPR) and the molecular
      link to cell survival and death mechanisms. We (i) delineate the mechanistic
      scenario and outcome of the UPR; (ii) discuss the role of ER stress in cancer
      development and progression; (iii) highlight the impact of various environmental
      conditions and stress stimuli, such as nutrient limitation and tumor hypoxia, in
      this context; and (iv) attempt to shed some light on the putative link between
      DNA damage, irradiation, and ER stress to emphasize the potential of therapeutic
      targeting of ER stress pathways for combined cancer treatments.

PMID- 29345570
TI  - The role of AMPK/mTOR modulators in therapy of acute myeloid leukemia.
AB  - Differentiation therapy of acute promyelocytic leukemia with all-trans retinoic
      acid represents the most successful pharmacological therapy of acute myeloid
      leukemia (AML). Numerous studies demonstrate that drugs that inhibit mechanistic
      target of rapamycin (mTOR) and activate AMP-kinase (AMPK) have beneficial effects
      in promoting differentiation and blocking proliferation of AML. Most of these
      drugs are already in use for other purposes; rapalogs as immunosuppressants,
      biguanides as oral antidiabetics, and 5-amino-4-imidazolecarboxamide
      ribonucleoside (AICAr, acadesine) as an exercise mimetic. Although most of these
      pharmacological modulators have been widely used for decades, their mechanism of
      action is only partially understood. In this review, we summarize the role of
      AMPK and mTOR in hematological malignancies and discuss the possible role of
      pharmacological modulators in proliferation and differentiation of leukemia
      cells.

PMID- 29345571
TI  - Targeting Cytosolic Phospholipase A2alpha for Novel Anti-Inflammatory Agents.
AB  - Group IV cytosolic phospholipase A2 (cPLA2alpha) plays a critical role in
      inflammatory processes. It produces arachidonic acid which is the main source of
      the pro-inflammatory eicosanoids mediators that are important in innate immune
      system. In some cases, these proinflammatory mediators cause damages to the host
      tissues and therefore promote autoimmune diseases. Consequently, development of
      potent inhibitors against cPLA2alpha could improve the therapy of inflammatory
      diseases. In the last two decades, intense efforts have been done to find potent
      cPLA2alpha inhibitors. Several scaffolds have been developed with the use of
      structure activity relationship (SAR) studies, and potent inhibitors have been
      obtained. The poor absorption of these compounds from intestine was the main
      challenge for clinical application. This review illustrates the search for
      cPLA2alpha inhibitors, their SAR studies and biological effects.

PMID- 29345572
TI  - Breaking the DNA damage response via serine/threonine kinase inhibitors to
      improve cancer treatment.
AB  - Multiple, both endogenous and exogenous, sources may induce DNA damage and DNA
      replication stress. Cells have developed DNA damage response (DDR) signaling
      pathways to maintain genomic stability and effectively detect and repair DNA
      lesions. Serine/threonine kinases such as Ataxia-telangiectasia mutated (ATM) and
      Ataxia-telangiectasia and Rad3-Related (ATR) are the major regulators of DDR,
      since after sensing stalled DNA replication forks, DNA double- or single-strand
      breaks, may directly phosphorylate and activate their downstream targets, that
      play a key role in DNA repair, cell cycle arrest and apoptotic cell death.
      Interestingly, key components of DDR signaling networks may constitute an
      attractive targets for anti-cancer therapy through two distinct potential
      approaches: as a chemo- and radiosensitizers to enhance the effectiveness of
      currently used genotoxic treatment or as a single agents to exploit defects in
      DDR in cancer cells via synthetic lethal approach. Moreover, the newest data
      reported that serine/threonine protein kinase R (PKR)-like endoplasmic reticulum
      kinase (PERK) is also closely associated with cancer development and progression.
      Thereby, utilization of small-molecule, serine/threonine kinase inhibitors may
      provide a novel, groundbreaking, anti-cancer treatment strategy. Currently, a
      range of potent, highly-selective toward ATM, ATR and PERK inhibitors has been
      discovered, but after foregoing study, additional investigations are necessary
      for their future clinical use.

PMID- 29345573
TI  - Precision Medicine: Update on Diagnosis and Therapeutic Strategies of
      Hepatocellular Carcinoma.
AB  - Recent advances in multiple omics technologies and the advent of massively
      parallel sequencing provide technical supports for the implementation of
      precision medicine. The precision medicine emphasizes that heterogeneous diseases
      can be well classified into more precise subtypes by the powerful detection
      methods and integration of clinical features, so that the clinicians should
      develop more accurate diagnosis and therapeutic strategies for the disease
      subtype population in an effort to maximize the efficacy and minimize the
      unnecessary side effects. Oncology is at the forefront of precision medicine, as
      malignant tumors have significant heterogeneity and are among the leading causes
      of death nationally and worldwide. The incidence and mortality of Hepatocellular
      Carcinoma (HCC), a kind of extraordinarily heterogeneous malignancy, have been
      increasing worldwide, making it a major public health concern. Such heterogeneity
      affects key signaling pathways, driving phenotypic variation, influences tumor
      evolution, and poses severe challenges to HCC treatment. The application of
      precision medicine will have certain impact on HCC diagnosis and treatment
      strategies. Herein, we summarize the updates and challenges in high-risk
      population screening, prevention, diagnosis, staging and therapy of HCC under the
      concept of precision medicine.

PMID- 29345574
TI  - Role of CD73 in Disease: Promising Prognostic Indicator and Therapeutic Target.
AB  - CD73, also known as ecto-5'-nucleotidase (eN, NT5E, EC3.13.5), is the
      ratelimiting enzyme for adenosine generation and is expressed on multiple cells.
      Its expression is significantly influenced by hypoxia and inflammatory factors.
      During inflammation, CD73 protects endothelial barrier function and inhibits
      leukocyte trafficking. CD73 also promotes M2 macrophages (anti-inflammatory
      phenotype). In addition, CD73 is expressed on Treg cells and mediates immune
      suppression through adenosine. CD73 serves as an essential regulator for the
      immunity and inflammation. Its expression is related to many diseases, such as
      autoimmune diseases, ischemia-reperfusion injuries, arterial calcifications, and
      atherosclerosis. CD73 is overexpressed in many cancers. Its expression is
      positively associated with tumor growth, metastasis, angiogenesis, poor prognosis
      and resistance to chemotherapy. Thus, CD73 may be used for prognostic indicator
      and therapeutic target in diseases such as cancers.

PMID- 29345575
TI  - Recent progress in chemosensors using aldehyde-bearing fluorophores for detection
      of specific analytes and its bioimaging.
AB  - In recent years, aldehyde-appended fluorescence probes are paid more and more
      attention by researchers. The fluorescent biological imaging provided many new
      applications today, which is often used for cell and tissue imaging in biomedical
      research. Meanwhile, the nucleophilic mechanism is a very simple and convenient
      procedure for the preparation of aldehyde-sensing probes. This tutorial review
      focuses on aldehyde-bearing chemosensors based on nucleophilic addition mechanism
      with biological applications.

PMID- 29345576
TI  - Radiotracers for Amyloid Imaging in Neurodegenerative Disease: State-of-the-Art
      and Novel Concepts.
AB  - The pathological accumulation of different peptides is the common base of many
      neurodegenerative processes, such as Alzheimer's disease (AD). AD is
      characterized by amyloid deposits which may cause alterations in
      neurotransmission, activation of inflammatory mechanisms, neuronal death and
      cerebral atrophy. Diagnosis in vivo is challenging as the criteria rely mainly on
      clinical manifestations, which become evident only in a late stage of the
      disease. While AD can currently be definitively confirmed by postmortem
      histopathologic examination, in vivo imaging may improve the clinician's ability
      to identify AD at the earliest stage. In this regard, the detection of cerebral
      amyloid plaques with positron emission tomography (PET) is likely to improve
      diagnosis and allow for a prompt start of an effective therapy. Many PET imaging
      probes for AD-specific pathological modifications have been developed and proved
      effective in detecting amyloid deposits in vivo. We here review the current
      knowledge on PET imaging in the detection of amyloid deposits and their
      application in the diagnosis of AD.

PMID- 29345577
TI  - Probiotics and Paraprobiotics in Viral Infection: Clinical Application and
      Effects on the Innate and Acquired Immune Systems.
AB  - Recently, the risk of viral infection has dramatically increased owing to changes
      in human ecology such as global warming and an increased geographical movement of
      people and goods. However, the efficacy of vaccines and remedies for infectious
      diseases is limited by the high mutation rates of viruses, especially, RNA
      viruses. Here, we comprehensively review the effectiveness of several probiotics
      and paraprobiotics (sterilized probiotics) for the prevention or treatment of
      virally-induced infectious diseases. We discuss the unique roles of these agents
      in modulating the cross-talk between commensal bacteria and the mucosal immune
      system. In addition, we provide an overview of the unique mechanism by which
      viruses are eliminated through the stimulation of type 1 interferon production by
      probiotics and paraprobiotics via the activation of dendritic cells. Although
      further detailed research is necessary in the future, probiotics and/or
      paraprobiotics are expected to be among the rational adjunctive options for the
      treatment of various viral diseases.

PMID- 29345578
TI  - Searching for New Targets and Treatments in the Battle Against Squamous Cell
      Carcinoma of the Head and Neck, with Specific Focus on Tumours of the Tongue.
AB  - Squamous cell carcinoma of the head and neck, SCCHN, is a heterogeneous group of
      tumours not only concerning the site of origin but also regarding aetiology. The
      5-year survival for the whole group of SCCHN tumours has not significantly
      improved over the last 20-25 years. Apart from tumour spread to lymph nodes, N
      status, gains and losses of specific chromosomes are the only factors shown to be
      independent prognostic markers for these tumours. Worldwide, an increasing number
      of people <= 40 years are seen being affected by tongue SCC, the most common
      tumour within the SCCHN group. Even without any clinical signs of metastasis, up
      to 30% of all tongue SCC have histologically detectable spread to lymph nodes. In
      this mini review, field cancerization, tumour microenvironment, the so called EMT
      (epithelial mesenchymal transition) process and the role of viruses in
      development of SCCHN are discussed as well as potential new therapeutic targets.
      For the group of tongue SCC, with the increasing incidence seen in young patients
      and particularly women, new data with impact on prognosis and treatment are
      urgently needed. But as long as data from the analyses of several sub sites are
      presented as valid for the whole group of tumours, this vital point is missed.

PMID- 29345579
TI  - Genistein as a Potential Anticancer Agent Against Head and Neck Squamous Cell
      Carcinoma.
AB  - The use of nutraceuticals as protection drugs against chronic diseases gained a
      vast success. Many studies found that nutraceuticals may reduce the tumorigenic
      actions of carcinogens, inhibiting the adhesion and proliferation of tumor cells.
      Genistein is a natural isoflavone preventing osteoporosis, menopause problems and
      heart diseases. It is also known in China and Japan for its anticancer
      properties. The available treatment protocols for Head and neck squamous cell
      cancer (HNSCC) have led to poor results and new therapies are necessary. In this
      paper, we will review anticancer therapeutic potential of genistein and in vitro
      and in vivo studies that suggest its potential role in the treatments of HNSCC.

PMID- 29345580
TI  - Multi-potent Natural Scaffolds Targeting Amyloid Cascade: In Search of
      Alzheimer's Disease Therapeutics.
AB  - Alzheimer's Disease (AD) once considered a rare disorder emerges as a major
      health concern in recent times. The disease pathogenesis is very complex and yet
      to be understood completely. However, "Amyloid Cascade" is the central event in
      disease pathogenesis. Several proteins of the amyloid cascade are currently being
      considered as potential targets for AD therapeutics discovery. Many potential
      compounds are in clinical trials, but till now there is no known cure for the
      disease. Recent years have witnessed remarkable research interest in the search
      of novel concepts in drug designing for AD. Multi-targeted ligand design is a
      paradigm shift in conventional drug discovery. In this process rather than
      designing ligands targeting a single receptor, novel ligands have been designed/
      synthesized that can simultaneously target many pathways involved in disease
      pathogenesis. Here, recent developments in computational drug designing protocols
      to identify multi-targeted ligand for AD have been discussed. Therapeutic
      potential of different multi-potent compounds also has been discussed briefly.
      Prime emphasis has been given to multi-potent ligand from natural resources.
      Polyphenols are an interesting group of compounds which show efficacy against a
      wide range of disease and have the property to exhibit multi-potency. Several
      groups attempted to identify novel multi-potent phytochemicals for AD therapy.
      Multi-potency of several polyphenols or compounds synthesized using the poly
      phenolic scaffolds have been briefly discussed here. However, the multi-targeted
      drug designing for AD is still in early stages, more advancement in drug
      designing method/algorithm developments is urgently required to discover more
      efficient compounds for AD therapeutics.

PMID- 29345583
TI  - Controversies in the Cath Lab: Navigating Contemporary Conundrums Before, During
      and After Intervention.

PMID- 29345581
TI  - Premorbid and Illness-related Social Difficulties in Eating Disorders: An
      Overview of the Literature and Treatment Developments.
AB  - BACKGROUND: Social difficulties in eating disorders can manifest as predisposing
      traits and premorbid difficulties, and/or as consequences of the illness.
      OBJECTIVE: The aim of this paper is to briefly review the evidence of social
      problems in people with eating disorders and to consider the literature on
      treatments that target these features. METHOD: A narrative review of the
      literature was conducted. RESULTS: People with eating disorders often manifest
      traits, such as shyness, increased tendency to submissiveness and social
      comparison, and problems with peer relationships before illness onset. Further
      social difficulties occur as the illness develops, including impaired social
      cognition and increased threat sensitivity. All relationships with family, peers
      and therapists are compromised by these effects. Thus, social difficulties are
      both risk and maintaining factors of eating disorders and are suitable targets
      for interventions. Several forms of generic treatments (e.g. interpersonal
      psychotherapy, cognitive analytic therapy, focal psychodynamic therapy) have an
      interpersonal focus and show some efficacy. Guided self-management based on the
      cognitive interpersonal model of the illness directed to both individuals and
      support persons has been found to improve outcomes for all parties. Adjunctive
      treatments that focus on specific social difficulties, such as cognitive
      remediation and emotion skills training and cognitive bias modification have been
      shown to have a promising role. CONCLUSION: More work is needed to establish
      whether these approaches can improve on the rather disappointing outcomes that
      are attained by currently used treatments for eating disorders.

PMID- 29345582
TI  - Is the Impact of Starvation on the Gut Microbiota Specific or Unspecific to
      Anorexia Nervosa? A Narrative Review Based on a Systematic Literature Search.
AB  - BACKGROUND: The role of the gut microbiota in Anorexia Nervosa (AN) has long been
      neglected by researchers, although the fact that the former is known to play an
      important role in health, disease and weight regulation. Cycles of overweight and
      underweight due to natural states of starvation and refeeding are normal in many
      vertebrates in their ecological niches. OBJECTIVE: The aim of this review was to
      compare the similarities and differences of the gut microbiota in eating
      disorders with conditions of fasting and refeeding in other vertebrates. METHOD:
      A systematic literature search was conducted in Pubmed and Web of Science to find
      all relevant studies examining the gut microbiota in eating disorders and
      different states of fasting in vertebrates for this narrative review. RESULTS:
      Gut microbiota appears to differ in AN versus normal-weight individuals. Induced
      fasting conditions in other vertebrates resulted in heterogeneous effects on gut
      microbiota with respect to their richness, diversity and community structures.
      The findings for hibernating animals were generally consistent. A decrease in
      microbial richness and diversity was observed in the hibernating animal compared
      to the active animal, and the community structures were linked to these
      conditions. Some similarities and differences between AN and different states of
      fasting in other vertebrates were found. CONCLUSION: The complexity of the
      relationship between fasting and gut microbiota is difficult to interprete. A
      deeper biological understanding is necessary to identify promising approaches for
      the modulation of the AN gut microbiota to support established psychotherapies.

PMID- 29345584
TI  - Mechanical Support in Cardiogenic Shock Complicating Acute Coronary Syndrome:
      Ready for Prime Time?
AB  - Cardiogenic Shock (CS) is a major challenge in current cardiology. Over the last
      decade, cardiogenic shock mortality has decreased somewhat, but it still remains
      high, particularly when associated with ischaemic heart disease. The challenges
      are numerous and include prevention, accurate diagnosis, prompt management and
      effective therapies to support a failing heart and prevent multi-organ failure.
      Despite improvements in the care of Acute Coronary Syndrome (ACS), it remains the
      most common cause of CS. In addition to existing medical therapy, mechanical
      circulatory support has been proposed for the management of ventricular failure.
      The intra-aortic balloon pump was amongst the first widely used percutaneous
      mechanical support devices, and more recently, systems providing a higher level
      of support have been developed. Although the evidence supporting their use is
      limited, they have the potential to significantly reduce CS-associated mortality.
      In this narrative review, we summarize the available evidence and discuss the
      future directions regarding percutaneous mechanical circulatory support in
      patients with left ventricular dysfunction and CS complicating ACS.

PMID- 29345585
TI  - Mandatory Reporting of Coronary Artery Calcifications Incidentally Noted on Chest
      Multi-Detector Computed Tomography: A Multicentre Experience.
AB  - BACKGROUND: Coronary Artery Calcifications (CACs) are associated with coronary
      atherosclerosis and Cardiovascular (CV) events. In "non-cardiovascular" settings,
      CACs can be easily detected on chest Multi-Detector Computed Tomography (MDCT).
      Their evaluation may help to better stratify CV risk in the general population,
      especially for primary prevention. AIMS: We retrospectively evaluated the
      relationship between CAC distribution and CV risk, determined by Framingham Risk
      Score (FRS), in a cohort of patients who underwent chest MDCT performed for
      several clinical indications. METHOD: We retrospectively recruited 305 patients
      (194 men, 111 women; mean age 70.5 years) from 3 different Italian centres.
      Patients with coronary stent, pacemaker and/or CV devices were excluded from the
      study. Circumflex Artery (LCX), Left Main Coronary Artery (LMCA), left Anterior
      Descending artery (LAD) and right coronary artery (RCA) were analysed. RESULTS:
      From a total population of 305 patients, 119 (39%) had low FRS (<10%), 115 (38%)
      had intermediate FRS (10-20%), and 71 (23%) had high FRS (>20%). The study
      identified 842 CACs located in decreasing order as follows: RCA (34.5%), LAD
      (32.3%), LCX (28%) and LMCA (13%). Statistical two-step analysis subdivided
      patients into two clusters according to FRS (risk threshold = 12.38%): cluster I
      (mean 9.34) and cluster II (mean 15.09). A significant association between CAC
      distribution and cluster II was demonstrated. CACs were mostly detected in
      patients with intermediate FRS. All patients (100%) with the highest CV risk
      showed intermediate RCA and LMCA involvement. CONCLUSION: Radiologists can note
      the distribution of CACs on a chest MDCT and should mandatorily record them in
      their reports. Depending on CAC presence and location, these findings may have
      important clinical implications, mostly in asymptomatic patients with
      intermediate FRS. This information may reclassify a patients' CV risk and improve
      clinical management.

PMID- 29345586
TI  - What is the Role of Cangrelor in Patients Undergoing PCI?
AB  - Dual antiplatelet therapy with aspirin and oral P2Y12-receptor inhibitors
      prevents ischemic events in patients undergoing Percutaneous Coronary
      Intervention (PCI). However, oral administration of antiplatelet drugs cause
      delay of onset of platelet inhibition in P2Y12-inhibitor naive patients.
      Cangrelor is a novel P2Y12-receptor inhibitor which is administrated
      intravenously and thus allows immediate antiplatelet inhibition during PCI. Due
      to its unique pharmacokinetics with fast onset of platelet inhibition and very
      short plasma half-life it allows effective and controllable periprocedural
      platelet inhibition. It could reduce short-term ischemic events in large
      randomized clinical trials. The present article reviews the available evidence
      and application on cangrelor use in clinical practice.

PMID- 29345587
TI  - Is there a Role for Oral Triple Therapy in Patients with Acute Coronary Syndromes
      Without Atrial Fibrillation?
AB  - BACKGROUND: Acute Coronary Syndrome (ACS) patients, despite treatment with Dual
      Anti- Platelet Therapy (DAPT), have up to 10% risk of recurrent Major Adverse
      Cardiac Events (MACE) in the short term. METHODS: Here we review studies using
      more potent antithrombotic agent combinations to reduce this risk, namely Triple
      Therapy (TT) with the addition of an oral anticoagulant, PAR-1 antagonist, or
      cilostazol to DAPT (mainly aspirin and clopidogrel), and discuss the limitations
      of trials to date. RESULTS: Generally speaking, TT leads to an increase in
      bleeding. Vorapaxar showed a signal for reducing ischaemic events, but increased
      intracranial haemorrhage 3-fold in the subacute phase of ACS, although remains an
      option for secondary prevention beyond the immediate subacute phase, particularly
      if prasugrel or ticagrelor are not available. Non-Vitamin K Oral Anticoagulants
      (NOACs) all increased bleeding, with only modest reduction in MACE noted with low
      dose rivaroxaban. Rivaroxaban can be considered combined with aspirin and
      clopidogrel in ACS patients at high ischaemic and low bleeding risk, without
      prior stroke/TIA. The combination of P2Y12 inhibitor and NOAC, without aspirin,
      looks promising. DAPT may be replaced, not by TT, but by dual therapy comprising
      a NOAC with a P2Y12 inhibitor. CONCLUSION: More potent antithrombotic regimens
      increase bleeding and should only be considered on an individual basis, after
      careful risk stratification. Accurate risk stratification of ACS patients, for
      both ischaemic and bleeding risk, is essential to allow individualised treatment.

PMID- 29345588
TI  - The Role of Percutaneous Coronary Intervention in the Treatment of Chronic Total
      Occlusions: Rationale and Review of the Literature.
AB  - BACKGROUND: Chronic total occlusion (CTO) of a coronary artery is defined as an
      occluded segment with no antegrade flow and a known or estimated duration of at
      least 12 weeks. OBJECTIVE: We considered the current literature describing the
      indications and clinical outcomes for de-novo CTO- percutaneous coronary
      intervention (PCI), and discuss the role of CTO-PCI and future directions for
      this procedure. METHOD: Databases (PubMed, the Cochrane Library, Embase, EBSCO,
      Web of Science, and CINAHL were searched and relevant studies of CTO-PCI were
      selected for review. RESULTS: The prevalence of coronary artery CTO's has been
      reported to be ~ 20% among patients undergoing diagnostic coronary angiography
      for suspected coronary artery disease. Revascularization of any CTO can be
      technically challenging and a time-consuming procedure with relatively low
      success rates and may be associated with a higher incidence of complications,
      particularly at non-specialized centers. However, with an increase in experience
      and technological advances, several centers are now reporting success rates above
      80% for these lesions. There is marked variability among studies in reporting
      outcomes for CTO-PCI with some reporting potential mortality benefit, better
      quality of life and improved cardiac function parameters. Anecdotally, properly
      selected patients who undergo a successful CTO-PCI most often have profound
      relief of ischemic symptoms. Intuitively, it makes sense to revascularize an
      occluded coronary artery with the goal of improving cardiovascular function and
      patient quality of life. CONCLUSIONS: CTO-PCI is a rapidly expanding specialized
      procedure in interventional cardiology and is reasonable or indicated if the
      occluded vessel is responsible for symptoms or in selected patients with silent
      ischemia in whom there is a large amount of myocardium at risk and PCI is likely
      to be successful.

PMID- 29345589
TI  - Neonatal Systemic Thrombosis: An Updated Overview.
AB  - Thromboembolic disease is a complex disorder with a multifactorial aetiology and
      a severe outcome. In newborns and children it may be missed or diagnosed late,
      thus worsening the prognosis. The neonatal disease is different from the disorder
      affecting older children and adults. However, scant epidemiological data and few
      randomised clinical trials regarding paediatric patients are available, and
      treatment recommendations are largely based on adult guidelines. Younger patients
      then have several decades over which they will suffer from the complications of
      thrombosis and risk of a new thrombotic episode. Current knowledge about neonatal
      thromboembolic disease and its prevention is reviewed here along with maternal,
      foetal, neonatal, pharmacological, environmental, lifestyle and occupational
      contributing factors. Additional data are urgently needed to improve diagnostic
      and therapeutic strategies and patient outcomes.

PMID- 29345590
TI  - What is the Role for Glycoprotein IIb/IIIa Inhibitor Use in the Catheterization
      Laboratory in the Current Era?
AB  - BACKGROUND: In the era of dual antiplatelet therapy of aspirin and clopidogrel
      and systematic stent implantation, Glycoprotein IIb/IIIa Inhibitors (GPI),
      including abciximab, eptifibatide and tirofiban, proved beneficial in improving
      early outcome of Percutaneous Coronary Intervention (PCI), especially in higher
      risk clinical and/or anatomical subsets. This was associated however, with an
      increased incidence of bleeding complications. OBJECTIVE: To review whether the
      established results of GPI in PCI are maintained in the contemporary era of more
      effective antiplatelet agents (i.e., prasugrel, ticagrelor and cangrelor) and
      safer anticoagulants (i.e., bivalirudin) and interventional techniques (i.e.,
      radial approach). METHODS: The most relevant evidence on the use of GPI in stable
      coronary artery disease, non-STelevation coronary syndromes and ST-elevation
      myocardial infarction was reviewed. RESULTS: Overall the relative efficacy and
      safety of GPI in contemporary PCI is maintained, largely irrespective of the use
      of more effective antiplatelet agents and/or safer anticoagulants and
      interventional techniques. However, an increase in the absolute occurrence of
      major and/or minor bleeding and/or need for blood transfusions is generally
      observed. CONCLUSION: Because of the persistent benefit of GPI in limiting early
      ischemic complications, especially in higher risk clinical and/or anatomical
      subsets, and the associated risk of increased bleeding complications, also in
      contemporary PCI, these agents should currently be used on a selective rather
      than routine basis, including bail out administration for peri-procedural
      thrombotic complications.

PMID- 29345591
TI  - Should Antithrombotic Treatment Strategies in East Asians Differ from Caucasians?
AB  - With over 1.5 billion people, East Asians are the most populous race in the
      world. Health status in this population is an important global issue. In the
      contemporary trials of antithrombotic treatment, East Asian patients have a lower
      risk for atherothrombotic diseases (especially, Coronary Artery Disease [CAD])
      and a higher risk for bleeding (especially, gastrointestinal bleeding and
      hemorrhagic stroke). Despite these observations, antithrombotic treatment
      strategies in East Asian patients are mainly based on the American or European
      guidelines that are derived from randomized, controlled trials including mostly
      Caucasians. Despite a low response to clopidogrel, East Asian patients with CAD
      show a similar or even a lower rate of ischemic event occurrence and higher
      bleeding risk compared with Caucasian patients. The latter is referred to as the
      "East Asian Paradox", suggesting a dissimilar therapeutic window for antiplatelet
      therapy than Caucasians. In addition, different net clinical benefits have been
      observed between the races with potent P2Y12 inhibitors that may be related to
      racial differences in pharmacokinetic and pharmacodynamic profiles. Furthermore,
      there is emerging concern regarding differences between East Asian vs. Western
      patients in pharmacodynamic and clinical efficacies of anticoagulant agents. We
      now summarize experimental and clinical evidence of the efficacy and safety of
      antithrombotic agents in the East Asian population. We suggest the concept of
      "race-tailored antithrombotic treatment" in CAD patients and/or in patients
      undergoing percutaneous coronary intervention.

PMID- 29345592
TI  - Prolonging Ticagrelor Beyond a Year of Acute Coronary Syndrome: Worth or Harmful?
AB  - Platelet activation plays a central role in triggering and complicating acute
      coronary syndromes, especially in case of stent thrombosis and myocardial
      infarction. On top of aspirin, P2Y12- inhibitors are successfully used to treat
      and prevent these events for a duration of one year after an acute coronary
      episode or 6 months after drug-eluting stent implantation. However, patients with
      acute coronary syndromes remain at heightened risk for recurrent ischemic events
      after the recommended durations of P2Y12-inhibitors and therefore, prolonging
      treatment is often considered in clinical practice. However, the higher risk for
      bleeding limits the utility of such approach to a restricted group who is still
      poorly defined by available measures. This review aims to discuss potential
      benefits and highlight important pitfalls of prolonged treatment with P2Y12
      inhibitors, with a focus on ticagrelor, an attractive reversible P2Y12-inhibitor
      in patients after myocardial infarction.

PMID- 29345593
TI  - Antithrombotic Therapy After TAVR.
AB  - Transvascular Aortic Valve Replacement (TAVR) has emerged as a treatment option
      in patients with severe aortic stenosis who are inoperable and has recently been
      evaluated in patients with intermediate surgical risk. The number of procedures
      is increasing worldwide in parallel with the demographic changes in industrial
      countries. The risk for cerebral embolism is of main concern and represents a
      major determinant for prognosis and quality of live after TAVR. The empiric
      antithrombotic therapy consists of Dual Antiplatelet Therapy (DAPT); However the
      risk-benefit of this approach is lacking evidence from randomized, placebo
      controlled trials regarding choice and duration of antithrombotic treatment.
      Although anticoagulation is generally not recommended in patients with aortic
      bioprosthesis without atrial fibrillation, there is current uncertainty whether
      combination of antiplatelet and anticoagulant therapy or anticoagulation alone
      might represent a more favorable antithrombotic regimen compared to the current
      empiric standard of DAPT. In addition, so far undetected atrial fibrillation is
      highly prevalent in the elderly population undergoing TAVR. In particular, the
      favorable safety profile of Non-Vitamin K Oral Anticoagulants (NOAC) offers an
      attractive option. A number of trials are currently underway to investigate the
      benefit of NOAC in patients with and without atrial fibrillation undergoing TAVR.
      The present article reviews the available evidence concerning stroke risk in TAVR
      patients and the current and future role of antithrombotic therapy during and
      after the procedure.

PMID- 29345594
TI  - Should STEMI Patients Receive Opiate Analgesia? The Morphine Paradox.
AB  - BACKGROUND: The very significant benefit of P2Y12 receptor inhibitor
      administration in patients with ST-elevation myocardial infarction (STEMI), in
      reducing future ischaemic events and stent thrombosis, is undisputed. Morphine
      analgesia is very frequently co-administered to these patients for pain relief,
      along with antiplatelet therapy, at the time of presentation, and prior to
      reperfusion with primary percutaneous coronary intervention. METHODS: Research
      and online content related to opiates use in STEMI was reviewed. Bibliographies
      of retrieved studies were searched manually for additional studies and reviews.
      RESULTS: There is sufficient data from pharmacokinetic and pharmacodynamic
      studies showing that the co-administration of morphine with oral P2Y12 receptor
      inhibitor results in delayed antiplatelet effects. However, whether this results
      in adverse outcomes remains unclear. Data from studies reporting the effect of
      morphine on clinical outcomes in STEMI are inconsistent, although they tend to be
      underpowered to show an effect on hard clinical outcomes, but some clearly show a
      relationship between morphine use and infarct size. Strategies to overcome the
      potentially significant negative impact of morphine on platelet reactivity in
      STEMI are discussed. CONCLUSION: Whilst clearly definitive, adequately powered,
      randomised controlled trials are lacking, we would recommend avoiding the
      combination of morphine with oral P2Y12 receptor inhibitors and recommend
      alternative strategies including intravenous platelet inhibitor strategies, in
      high risk patients.

PMID- 29345595
TI  - Hospital Management of Severe Hypertriglyceridemia in Children.
AB  - BACKGROUND: Severe Hypertriglyceridemia (HTG), i.e., plasma triglyceride levels
      exceeding 1000 mg/dL, is one of the established causes of acute pancreatitis and
      severe abdominal pain. There are no established pediatric guidelines regarding
      treatment of children and adolescents with severe HTG. OBJECTIVE: To review the
      pathophysiology and etiology of severe HTG in the pediatric age group, and to
      discuss management options. METHOD AND RESULTS: Severe HTG is usually due to
      deficient or absent Lipoprotein Lipase (LPL) activity, which can be due to
      primary genetic etiology or secondary causes triggering HTG in those with
      underlying genetic susceptibility. Hospitalization is indicated for patients with
      severe HTG who are symptomatic with abdominal pain or pancreatitis, in those with
      uncontrolled diabetes requiring insulin, or, in those with substantial elevations
      of plasma TG. Fasting followed by fat free diet until plasma TG declines to
      <1000mg/dL is essential. Subsequently, stringent fat restriction followed by
      slowly increasing the dietary fat while maintaining the plasma TG concentration
      at a targeted level is recommended. Insulin infusions are helpful in patients who
      have some LPL activity, especially in those with diabetes. Plasmapheresis may be
      considered in those with severe pancreatitis, shock or multi-organ failure.
      Medications such as fibrates and omega-3 fatty acids are not effective if LPL
      activity is absent or when plasma TG is >1800 mg/dL. Medications only have an
      adjunct role in the management. Low fat diet, lifestyle changes, weight loss,
      control of secondary causes, and patient education form the mainstay of
      management once the patient is discharged.

PMID- 29345596
TI  - The Coronary Artery Risk Detection in Appalachian Communities (CARDIAC) Project:
      An 18 Year Review.
AB  - BACKGROUND: The Coronary Artery Risk Detection in Appalachian Communities
      (CARDIAC) Project is a chronic disease risk factor surveillance, intervention,
      and research initiative aimed at combating the unacceptably high prevalence of
      heart disease, diabetes, and other chronic illnesses in West Virginia. OBJECTIVES
      AND METHODS: The school-based public health project identifies health risk
      factors in children, educates families, informs primary care physicians, and
      provides resources to schools to help improve population health, beginning with
      children. RESULTS AND CONCLUSION: Details regarding methodology, results, and
      conclusions derived from this unique public health initiative that has screened
      over 200,000 children are the subject of this 18- year review.

PMID- 29345597
TI  - Pediatric Markers of Adult Cardiovascular Disease.
AB  - BACKGROUND: Cardiovascular diseases are the leading cause of death worldwide.
      While cardiovascular disease typically does not occur until adulthood, the
      pathogenesis of atherosclerotic cardiovascular disease starts in early childhood.
      OBJECTIVE: The purpose of this review is to describe the evidence that the
      process of atherosclerosis begins in childhood, as well as identify the risk
      factors present in childhood that are associated with the presence of
      atherosclerotic cardiovascular disease in childhood as well as future
      cardiovascular events in adulthood. RESULTS AND CONCLUSION: There is much
      accumulating evidence linking modifiable risk factors that are already present in
      childhood and that strongly predict future cardiovascular disease. The selective
      targeting of modifiable risk factors in childhood, including body mass index,
      holds promise in reducing the burden of adult cardiovascular disease. Future
      research studies should focus on elucidating the mechanisms which drive the
      pathogenesis of atherosclerosis in childhood and young adulthood, as well as
      identifying which interventions are most effective at limiting the progression of
      atherosclerosis and thus reducing future cardiovascular disease.

PMID- 29345598
TI  - Dolutegravir-Related Neurological Adverse Events: A Case Report of Successful
      Management with Therapeutic Drug Monitoring.
AB  - OBJECTIVE: Dolutegravir (DTG), a highly effective second-generation HIV integrase
      inhibitor with high genetic barrier to resistance, has shown excellent
      tolerability and safety profiles in clinical trials. However, some patients may
      experience neurological or psychiatric adverse effects leading to DTG
      discontinuation. CASE REPORT: This report describes a case of 29-year-old woman
      who developed neurological adverse events after starting the DTG-based
      antiretroviral therapy. Serum DTG concentrations were supratherapeutic which has
      required a dosing interval adjustment. The findings of this case report suggest
      that Therapeutic Drug Monitoring might be useful in individuals expressing
      unusual DTG pharmacokinetics.

PMID- 29345599
TI  - Crystalline Ethylene Oxide and Propylene Oxide Triblock Copolymer Solid
      Dispersion Enhance Solubility, Stability and Promoting Time- Controllable Release
      of Curcumin.
AB  - AIMS AND BACKGROUND: The design and development of an effective medicine are,
      however, often faced with a number of challenges. One of them is the close
      relationship of drug's bioavailability with solubility, dissolution rate and
      permeability. The use of curcumin's (CUR) therapeutic potential is limited by its
      poor water solubility and low chemical stability. The purpose was to evaluate the
      effect of polymer and solid dispersion (SD) preparation techniques to enhance the
      aqueous solubility, dissolution rate and stability of the CUR. The recent patents
      on curcumin SD were reported as (i) curcumin with polyvinylpyrrolidone (CN20071
      32500 20071214, WO2006022012 and CN20151414227 20150715), (ii) curcumin
      zinc/polyvinylpyrrolidone (CN20151414227 20150715), (iii) curcumin-poloxamer 188
      (CN2008171177 20080605), (iv) curcumin SD prepared by melting method
      (CN20161626746-20160801). MATERIALS AND METHODS: SD obtained by co-preciptation
      or microwave fusion and the physical mixture of CUR with Poloxamer-407 (P-407),
      Hydroxypropylmetylcellulose-K4M (HPMC K4M) and Polyvinylpyrrolidone-K30 (PVP-K30)
      were prepared at the ratios of 1:2; 1:1 and 2:1. The samples were evaluated by
      solubility, stability, dissolution rate and characterized by SEM, PXRD, DSC and
      FTIR. RESULTS: The solubility, stability (pH 7.0) and dissolution rate were
      significantly greater for SD (CUR:P-407 1:2). The PXRD,SEM and DSC indicated a
      change in the crystalline state of CUR. The enhancement of solubility was
      dependent on a combination of factors including the weight ratio, preparation
      techniques and carrier properties. The drug release data fitted well with the
      Weibull equation, indicating that the drug release was controlled by diffusion,
      polymer relaxation and erosion occurring simultaneously. CONCLUSION: Thus, these
      SDs, specifically CUR:P-407 1:2 w/w, can overcome the barriers of poor
      bioavailability to reap many beneficial properties.

PMID- 29345600
TI  - An Open-Source Storage Solution for Cryo-Electron Microscopy Samples.
AB  - Cryo-electron microscopy (cryo-EM) enables the study of biological structures in
      situ in great detail and to solve protein structures at Angstrom level
      resolution. Due to recent advances in instrumentation and data processing, the
      field of cryo-EM is a rapidly growing. Access to facilities and national centers
      that house the state-of-the-art microscopes is limited due to the ever-rising
      demand, resulting in long wait times between sample preparation and data
      acquisition. To improve sample storage, we have developed a cryo-storage system
      with an efficient, high storage capacity that enables sample storage in a highly
      organized manner. This system is simple to use, cost-effective and easily
      adaptable for any type of grid storage box and dewar and any size cryo-EM
      laboratory.

PMID- 29345601
TI  - Vaccine effectiveness and use of collar impregnated with insecticide for reducing
      incidence of Leishmania infection in dogs in an endemic region for visceral
      leishmaniasis, in Brazil.
AB  - Although a national programme for control of visceral leishmaniosis (VL) is being
      run in Brazil, the disease continues to spread. This programme is essentially
      based on culling infected dogs from endemic regions. Thus, there is an urgent
      need to develop other control measures against VL to deter its advance. Here, a
      subunit vaccine, a recombinant vaccine, an insecticide-impregnated collar and the
      associations between these measures were evaluated for reducing the incidence of
      Leishmania infection in dogs. This was through a cohort study conducted in an
      endemic region of Brazil, considering the incidence and time of total exposure
      over a period of 1 year. The incidence of VL was estimated by means of
      serological and molecular diagnostic tests, 180 and 360 days after the
      application of the control measures. The estimates of the effectiveness (EF) were
      not significant in any cohort. The EF of the subunit vaccine, the recombinant
      vaccine and the collar were 26.4%, 32.8% and 57.7% and the upper limit of the 95%
      confidence interval for EF were 63.7%, 67.9% and 82.5%, respectively. In
      conclusion, under the conditions of this study, none of the immunogens for VL
      control was sufficiently effective to protect dogs against infection. On the
      other hand, use of collars impregnated with insecticide seems to constitute a
      method with better prognosis, corroborating other studies in this field.

PMID- 29345602
TI  - The mental health of adolescents and pre-adolescents living with inherited
      arrhythmia syndromes: a systematic review of the literature.
AB  - Potentially fatal arrhythmias add to the mental health challenges of adolescence.
      This systematic review sought to summarise current knowledge regarding the mental
      health of adolescents and pre-adolescents diagnosed with inherited arrhythmia
      syndromes. Searches combining psychological problems with inherited cardiac
      arrhythmia diagnoses identified 16 studies with paediatric (<18 years) inherited
      arrhythmia patients. All studies were cross-sectional; 8/16 required an
      implantable cardioverter defibrillator. Methods were quantitative (n=11),
      qualitative (n=4), or mixed (n=1), with 14-100% of participants having an
      inherited arrhythmia syndrome. Mean/median age in 13/16 studies was 12-16 years.
      Patients and parents reported lower quality of life, particularly in relation to
      physical function, social relationships, restriction of peer activities, bodily
      pain, and mental and emotional health. Self-perceptions and behaviour were
      similar to healthy populations. Rates of anxiety and depression (15-33% of these
      patients) were not increased in these studies where patients were assessed 2+
      years after diagnosis. Higher mental health risk occurred among patients who have
      a diagnosed sibling, those with cardiomyopathy, and those who report decreased
      quality of life. Mental health research among youth with inherited arrhythmias is
      extremely limited and of low quality. Data, primarily from patients 2-4 years
      after diagnosis or treatment with an implantable cardioverter defibrillator,
      indicate that quality of life may be decreased and 15-33% experience mental
      health issues. Future research is required to examine the mental health and
      quality of life of paediatric patients with inherited arrhythmia syndromes,
      whether or not they have an implantable cardioverter defibrillator, from time of
      diagnosis.

PMID- 29345603
TI  - Association between household food security and infant feeding practices in urban
      informal settlements in Nairobi, Kenya.
AB  - Studies in urban informal settlements show widespread inappropriate infant and
      young child feeding (IYCF) practices and high rates of food insecurity. This
      study assessed the association between household food security and IYCF practices
      in two urban informal settlements in Nairobi, Kenya. The study adopted a
      longitudinal design that involved a census sample of 1110 children less than 12
      months of age and their mothers aged between 12 and 49 years. A questionnaire was
      used to collect information on: IYCF practices and household food security.
      Logistic regression was used to determine the association between food insecurity
      and IYFC practices. The findings showed high household food insecurity; only
      19.5% of the households were food secure based on Household Insecurity Access
      Score. Infant feeding practices were inappropriate: 76% attained minimum meal
      frequency; 41% of the children attained a minimum dietary diversity; and 27%
      attained minimum acceptable diet. With the exception of the minimum meal
      frequency, infants living in food secure households were significantly more
      likely to achieve appropriate infant feeding practices than those in food
      insecure households: minimum meal frequency (adjusted odds ratio (AOR)=1.26,
      P=0.530); minimum dietary diversity (AOR=1.84, P=0.046) and minimum acceptable
      diet (AOR=2.35, P=0.008). The study adds to the existing body of knowledge by
      demonstrating an association between household food security and infant feeding
      practices in low-income settings. The findings imply that interventions aimed at
      improving infant feeding practices and ultimately nutritional status need to also
      focus on improving household food security.

PMID- 29345604
TI  - A new approach of three-dimensional guidance in paediatric cath lab: segmented
      and tessellated heart models for cardiovascular interventions in CHD.
AB  - BACKGROUND: Optimal imaging is essential for catheter-based interventions in CHD.
      The three-dimensional models in volume-rendering technique currently in use are
      not standardised. This paper investigates the feasibility and impact of novel
      three-dimensional guidance with segmented and tessellated three-dimensional heart
      models in catheterisation of CHD. In addition, a nearly radiation-free two- to
      three-dimensional registration and a biplane overlay were used.Methods and
      resultsWe analysed 60 consecutive cases in which segmented tessellated three
      dimensional heart models were merged with live fluoroscopy images and aligned
      using the tracheal bifurcation as a fiducial mark. The models were generated from
      previous MRI or CT by dedicated medical software. We chose the stereo-lithography
      format, as this promises advantage over volume-rendering-technique models
      regarding visualisation. Prospects, potential benefits, and accuracy of the two-
      to three-dimensional registration were rated separately by two paediatric
      interventionalists on a five-point Likert scale. Fluoroscopy time, radiation
      dose, and contrast dye consumption were evaluated. Over a 10-month study period,
      two- to three-dimensional image fusion was applied to 60 out of 354 cases. Of the
      60 catheterisations, 73.3% were performed in the context of interventions. The
      accuracy of two- to three-dimensional registration was sufficient in all cases.
      Three-dimensional guidance was rated superior to conventional biplane imaging in
      all 60 cases. We registered significantly smaller amounts of used contrast dye
      (p<0.01), lower levels of radiation dose (p<0.02), and less fluoroscopy time
      (p<0.01) during interventions concerning the aortic arch compared with a control
      group. CONCLUSIONS: Two- to three-dimensional image fusion can be applied
      successfully in most catheter-based interventions of CHD. Meshes in stereo
      lithography format are accurate and base for standardised and reproducible three
      dimensional models.

PMID- 29345605
TI  - Histopathological evaluation of aortic coarctation after conventional balloon
      angioplasty in neonates.
AB  - BACKGROUND: Optimal management strategy for native aortic coarctation in neonates
      and young infants is still a matter of debate. The surgical procedure,
      histopathologic research, and clinical outcome in 15 neonates who underwent
      surgery after successful balloon angioplasty is the basis of this study. METHOD:
      Between 01 October, 2014 and 01 August, 2017, we enrolled 15 patients with native
      aortic coarctation for this study. These patients had complications regarding
      recoarctation, following balloon angioplasty intervention at our institute and
      other centres. Surgically extracted parts were examined histopathologically and
      patient's data were collected retrospectively.ResultThe reasons for recurrence of
      recoarctation after balloon angioplasty are as follows: patients with higher
      preoperative echocardiographic gradients had recoarctation earlier, neointimal
      proliferation, aortic intimal fibrosis at the region of ductal insertion, and
      ductal residual tissue debris after balloon angioplasty. No repeat intervention
      was required in the 15 patients who underwent surgery followed by balloon
      angioplasty. Early mortality was seen in one patient after surgery. Postoperative
      complication in the surgical group occurred in the form of chylothorax in one
      patient. CONCLUSION: In centres in which the neonatal ICU is inexperienced,
      balloon angioplasty is particularly recommended. In developing neonatal clinics,
      balloon angioplasty, when performed on patients at their earliest possible age,
      delays actual corrective operation to a later date, which in turn provides less
      risky surgical outcomes in infants who are gaining weight, growing, and do not
      have any haemodynamic complaints.

PMID- 29345606
TI  - Prevalence of transmitted drug resistance among HIV-1 treatment-naive patients in
      Beijing.
AB  - To optimise patients' outcomes and gain insight into transmitted drug resistance
      (TDR) among human immunodeficiency virus (HIV)-1 treatment-naive patients in
      Beijing, the prevalence of TDR was assessed. Demographic and clinical data of
      1241 treatment-naive patients diagnosed between April 2014 and February 2015 were
      collected. TDR was defined using the Stanford University HIV drug resistance
      mutations database. The risk factors were evaluated by multi-logistic regression
      analysis. Among 932 successfully amplified cases, most were male (96.78%) and
      infected through men having sex with men (91.74%). Genotype were CRF01_AE
      (56.44%), B (20.60%), CRF07_BC (19.96%), C (1.61%) and other genotypes (1.39%).
      The overall prevalence of TDR was 6.12%. Most frequent mutations occurred in non
      nucleoside reverse transcriptase inhibitors (NNRTIs) (3.11%), followed by
      protease inhibitors (PIs) (2.25%) and nucleoside reverse transcriptase inhibitors
      (NRTIs) (1.32%). Furthermore, HIV-1 genotype was associated with high risk of
      resistance, in which genotype C and other genotype may have higher risk for
      resistance. The prevalence among treatment-naive patients in Beijing was low.
      Resistance to NNRTIs was higher than with PIs or NRTIs. Continuous monitoring of
      regional levels of HIV-1 TDRs would contribute to improve treatment outcomes and
      prevent failures.

PMID- 29345607
TI  - The Impact of Isolation Precautions on Hand Hygiene Frequency by Healthcare
      Workers.

PMID- 29345608
TI  - Food choices to meet nutrient recommendations for the adult Brazilian population
      based on the linear programming approach.
AB  - OBJECTIVE: To identify optimal food choices that meet nutritional recommendations
      to reduce prevalence of inadequate nutrient intakes. DESIGN: Linear programming
      was used to obtain an optimized diet with sixty-eight foods with the least
      difference from the observed population mean dietary intake while meeting a set
      of nutritional goals that included reduction in the prevalence of inadequate
      nutrient intakes to <=20 %. SETTING: Brazil. SUBJECTS: Participants (men and
      women, n 25 324) aged 20 years or more from the first National Dietary Survey
      (NDS) 2008-2009. RESULTS: Feasible solution to the model was not found when all
      constraints were imposed; infeasible nutrients were Ca, vitamins D and E, Mg, Zn,
      fibre, linolenic acid, monounsaturated fat and Na. Feasible solution was obtained
      after relaxing the nutritional constraints for these limiting nutrients by
      including a deviation variable in the model. Estimated prevalence of nutrient
      inadequacy was reduced by 60-70 % for most nutrients, and mean saturated and
      trans-fat decreased in the optimized diet meeting the model constraints.
      Optimized diet was characterized by increases especially in fruits (+92 g), beans
      (+64 g), vegetables (+43 g), milk (+12 g), fish and seafood (+15 g) and whole
      cereals (+14 g), and reductions of sugar-sweetened beverages (-90 g), rice (-63
      g), snacks (-14 g), red meat (-13 g) and processed meat (-9.7 g). CONCLUSION:
      Linear programming is a unique tool to identify which changes in the current diet
      can increase nutrient intake and place the population at lower risk of nutrient
      inadequacy. Reaching nutritional adequacy for all nutrients would require major
      dietary changes in the Brazilian diet.

PMID- 29345609
TI  - Dietary patterns and their association with adiponectin and leptin concentrations
      throughout pregnancy: a prospective cohort.
AB  - The aim of this study was to evaluate the association of dietary patterns (DP)
      with maternal adiposity indicators, leptin, adiponectin and insulin
      concentrations during pregnancy. A prospective cohort of pregnant women followed
      up at the 5th-13th, 20th -26th and 30th-36th gestational weeks and 30-40 d
      postpartum was conducted in Rio de Janeiro. A FFQ was administered in the third
      trimester (30th-36th gestational weeks). The reduced rank regression procedure
      was used to identify DP that explain response variables (dietary fibre and total
      fat) related to indicators of maternal adiposity (postpartum weight retention and
      gestational weight gain (GWG) adequacy), and plasma leptin, adiponectin and
      insulin concentrations. The associations between tertiles of DP and the outcomes
      were determined using logistic regression or longitudinal linear mixed-effect
      regression models. The mean daily energy intake during pregnancy was 10 104 (sd
      3234) kJ (2415 (sd 773) kcal), and GWG was 11.9 (sd 4.2) kg. In all, 40 % of
      women presented pre-gestational overweight/obesity. Excessive GWG occurred in
      34.7 % of pregnant women and 56.6 % were overweight/obese at postpartum. The
      'common-Brazilian' DP (characterised by higher intake of beans, rice and lower
      intake of fast food/snacks, candies/table sugar and processed meats/bacon) was
      positively associated with adiponectin (beta=1.07; 95 % CI 0.17, 1.98). The
      'Western' DP (characterised by higher intake of fast food/snacks and processed
      meat/bacon and lower intake of noodles/pasta/roots/tubers and sodas) was
      negatively associated with adiponectin (beta=-1.11; 95 % CI -2.00, -0.22) and
      positively associated with leptin concentrations (beta=64.9; 95 % CI 22.8, 107.0)
      throughout pregnancy. It may be suggested that the 'common-Brazilian' is a
      healthy DP and beneficial for serum concentrations of adiponectin and leptin.

PMID- 29345610
TI  - Adherence to Central-Line Insertion Practices (CLIP) with Peripherally Inserted
      Central Catheters (PICC) and Central Venous Catheters (CVC): A Prospective Study
      of 50 Hospitals in China.

PMID- 29345611
TI  - Accuracy of Provider-Selected Indications for Antibiotic Orders.
AB  - Documentation of antibiotic indication provides helpful information for
      antimicrobial stewardship, but accuracy is not understood. Review of 396
      antibiotic orders in a pediatric ICU and adult medicine step-down unit found 90%
      agreement between provider-selected indication and independent review. Prompts to
      enter antibiotic indication during order entry provide largely accurate
      information. Infect Control Hosp Epidemiol 2018;39:111-113.

PMID- 29345612
TI  - Fit Characteristics of N95 Filtering Facepiece Respirators and the Accuracy of
      the User Seal Check among Koreans.
AB  - Adequate facepiece fit of N95 filtering facepiece respirators (FFRs) is crucial
      for optimal protection against airborne pathogens. The quantitative fit test
      (QNFT) pass rates of the 4 N95 FFR models commonly used in Korea were below 50%.
      Male sex was identified as a single independent predictive factor for QNFT pass.
      Infect Control Hosp Epidemiol 2018;39:104-107.

PMID- 29345613
TI  - Comparative transcriptomics of Aspergillus fumigatus strains upon exposure to
      human airway epithelial cells.
AB  - Aspergillus fumigatus is an opportunistic, ubiquitous, saprophytic mould that can
      cause severe allergic responses in atopic individuals as well as life-threatening
      infections in immunocompromised patients. A critical step in the establishment of
      infection is the invasion of airway epithelial cells by the inhaled fungi.
      Understanding how A. fumigatus senses and responds to airway cells is important
      to understand the pathogenesis of invasive pulmonary aspergillosis. Here, we
      analysed the transcriptomes of two commonly used clinical isolates, Af293 and
      CEA10, during infection of the A549 type II pneumocyte cell line in vitro. We
      focused our RNA-seq analysis on the core set of genes that are present in the
      genomes of the two strains. Our results suggest that: (a) A. fumigatus does not
      mount a conserved transcriptional response to airway epithelial cells in our in
      vitro model and (b) strain background and time spent in the tissue culture media
      have a greater impact on the transcriptome than the presence of host cells. Our
      analyses reveal both common and strain-specific transcriptional programmes that
      allow for the generation of hypotheses about gene function as it pertains to
      pathogenesis and the significant phenotypic heterogeneity that is observed among
      A. fumigatus isolates.

PMID- 29345615
TI  - Variability in neural networks.
AB  - Experiments on neurons in the heart system of the leech reveal why rhythmic
      behaviors differ between individuals.

PMID- 29345614
TI  - Output variability across animals and levels in a motor system.
AB  - Rhythmic behaviors vary across individuals. We investigated the sources of this
      output variability across a motor system, from the central pattern generator
      (CPG) to the motor plant. In the bilaterally symmetric leech heartbeat system,
      the CPG orchestrates two coordinations in the bilateral hearts with different
      intersegmental phase relations (Deltaphi) and periodic side-to-side switches.
      Population variability is large. We show that the system is precise within a
      coordination, that differences in repetitions of a coordination contribute little
      to population output variability, but that differences between bilaterally
      homologous cells may contribute to some of this variability. Nevertheless, much
      output variability is likely associated with genetic and life history differences
      among individuals. Variability of Deltaphi were coordination-specific: similar at
      all levels in one, but significantly lower for the motor pattern than the CPG
      pattern in the other. Mechanisms that transform CPG output to motor neurons may
      limit output variability in the motor pattern.

PMID- 29345616
TI  - Inhibition of oxidative stress in cholinergic projection neurons fully rescues
      aging-associated olfactory circuit degeneration in Drosophila.
AB  - Loss of the sense of smell is among the first signs of natural aging and
      neurodegenerative diseases such as Alzheimer's and Parkinson's. Cellular and
      molecular mechanisms promoting this smell loss are not understood. Here, we show
      that Drosophila melanogaster also loses olfaction before vision with age. Within
      the olfactory circuit, cholinergic projection neurons show a reduced odor
      response accompanied by a defect in axonal integrity and reduction in synaptic
      marker proteins. Using behavioral functional screening, we pinpoint that
      expression of the mitochondrial reactive oxygen scavenger SOD2 in cholinergic
      projection neurons is necessary and sufficient to prevent smell degeneration in
      aging flies. Together, our data suggest that oxidative stress induced axonal
      degeneration in a single class of neurons drives the functional decline of an
      entire neural network and the behavior it controls. Given the important role of
      the cholinergic system in neurodegeneration, the fly olfactory system could be a
      useful model for the identification of drug targets.

PMID- 29345617
TI  - Loss of functional BAP1 augments sensitivity to TRAIL in cancer cells.
AB  - Malignant mesothelioma (MM) is poorly responsive to systemic cytotoxic
      chemotherapy and invariably fatal. Here we describe a screen of 94 drugs in 15
      exome-sequenced MM lines and the discovery of a subset defined by loss of
      function of the nuclear deubiquitinase BRCA associated protein-1 (BAP1) that
      demonstrate heightened sensitivity to TRAIL (tumour necrosis factor-related
      apoptosis-inducing ligand). This association is observed across human early
      passage MM cultures, mouse xenografts and human tumour explants. We demonstrate
      that BAP1 deubiquitinase activity and its association with ASXL1 to form the
      Polycomb repressive deubiquitinase complex (PR-DUB) impacts TRAIL sensitivity
      implicating transcriptional modulation as an underlying mechanism. Death receptor
      agonists are well-tolerated anti-cancer agents demonstrating limited therapeutic
      benefit in trials without a targeting biomarker. We identify BAP1 loss-of
      function mutations, which are frequent in MM, as a potential genomic
      stratification tool for TRAIL sensitivity with immediate and actionable
      therapeutic implications.

PMID- 29345618
TI  - NECAPs are negative regulators of the AP2 clathrin adaptor complex.
AB  - Eukaryotic cells internalize transmembrane receptors via clathrin-mediated
      endocytosis, but it remains unclear how the machinery underpinning this process
      is regulated. We recently discovered that membrane-associated muniscin proteins
      such as FCHo and SGIP initiate endocytosis by converting the AP2 clathrin adaptor
      complex to an open, active conformation that is then phosphorylated (Hollopeter
      et al., 2014). Here we report that loss of ncap-1, the sole C. elegans gene
      encoding an adaptiN Ear-binding Coat-Associated Protein (NECAP), bypasses the
      requirement for FCHO-1. Biochemical analyses reveal AP2 accumulates in an open,
      phosphorylated state in ncap-1 mutant worms, suggesting NECAPs promote the
      closed, inactive conformation of AP2. Consistent with this model, NECAPs
      preferentially bind open and phosphorylated forms of AP2 in vitro and localize
      with constitutively open AP2 mutants in vivo. NECAPs do not associate with
      phosphorylation-defective AP2 mutants, implying that phosphorylation precedes
      NECAP recruitment. We propose NECAPs function late in endocytosis to inactivate
      AP2.

PMID- 29345619
TI  - miR-9 regulates basal ganglia-dependent developmental vocal learning and adult
      vocal performance in songbirds.
AB  - miR-9 is an evolutionarily conserved miRNA that is abundantly expressed in Area
      X, a basal ganglia nucleus required for vocal learning in songbirds. Here, we
      report that overexpression of miR-9 in Area X of juvenile zebra finches impairs
      developmental vocal learning, resulting in a song with syllable omission, reduced
      similarity to the tutor song, and altered acoustic features. miR-9 overexpression
      in juveniles also leads to more variable song performance in adulthood, and
      abolishes social context-dependent modulation of song variability. We further
      show that these behavioral deficits are accompanied by downregulation of FoxP1
      and FoxP2, genes that are known to be associated with language impairments, as
      well as by disruption of dopamine signaling and widespread changes in the
      expression of genes that are important in circuit development and functions.
      These findings demonstrate a vital role for miR-9 in basal ganglia function and
      vocal communication, suggesting that dysregulation of miR-9 in humans may
      contribute to language impairments and related neurodevelopmental disorders.

PMID- 29345621
TI  - Circulating Helper T-Cell Subsets and Regulatory T Cells in Patients With Common
      Variable Immunodeficiency Without Known Monogenic Disease.
AB  - BACKGROUND: Common variable immunodeficiency (CVID) is the most common
      symptomatic primary immunodeficiency (PID). It is characterized by heterogeneous
      clinical manifestations and defects in B cells and T cells. In the present study,
      we investigated helper T (TH) cell subsets and regulatory T (Treg) cells and
      their related cytokines and transcription factors in CVID patients with no
      definitive genetic diagnosis. METHODS: The study population comprised 13 CVID
      patients and 13 healthy controls. Mutation analysis was performed using whole
      exome sequencing in CVID patients to rule out monogenic PIDs. TH subsets and Treg
      were analyzed using flow cytometry. The expression of determinant cytokines (IFN
      gamma, IL-17, IL-22, and IL-10) and cell subset specific transcription factors
      was evaluated before and after stimulation. RESULTS: The main clinical
      presentations of these patients were infections only and lymphoproliferative
      phenotypes. No autoimmune or allergy phenotypes were recorded. The frequencies of
      CD4+ T cells, TH17, and Treg cells were significantly reduced in CVID patients;
      however, TH1, TH1-like TH17, and TH22 subsets were normal. After stimulation,
      expression of retinoic-acid-orphan-receptor-C (RORC), runtrelated transcription
      factor 1 (RUNX1), IL17, and IL10 was significantly lower in CVID patients than in
      the healthy controls. Moreover, the concentration of IL-17 and IL-10 in the cell
      culture supernatants of stimulated CD4+ T cells was lower in CVID patients than
      in healthy controls. CONCLUSIONS: Our findings demonstrate that the imbalance of
      TH17 and Tregs could be associated with infection and the lymphoproliferative
      phenotype in CVID patients without monogenic disorders.

PMID- 29345620
TI  - Functional role of the type 1 pilus rod structure in mediating host-pathogen
      interactions.
AB  - Uropathogenic E. coli (UPEC), which cause urinary tract infections (UTI), utilize
      type 1 pili, a chaperone usher pathway (CUP) pilus, to cause UTI and colonize the
      gut. The pilus rod, comprised of repeating FimA subunits, provides a structural
      scaffold for displaying the tip adhesin, FimH. We solved the 4.2 A resolution
      structure of the type 1 pilus rod using cryo-electron microscopy. Residues
      forming the interactive surfaces that determine the mechanical properties of the
      rod were maintained by selection based on a global alignment of fimA sequences.
      We identified mutations that did not alter pilus production in vitro but reduced
      the force required to unwind the rod. UPEC expressing these mutant pili were
      significantly attenuated in bladder infection and intestinal colonization in
      mice. This study elucidates an unappreciated functional role for the molecular
      spring-like property of type 1 pilus rods in host-pathogen interactions and
      carries important implications for other pilus-mediated diseases.

PMID- 29345622
TI  - Position paper on nasal obstruction: evaluation and treatment.
AB  - Nasal obstruction (NO) is defined as the subjective perception of discomfort or
      difficulty in the passage of air through the nostrils. It is a common reason for
      consultation in primary and specialized care and may affect up to 30%-40% of the
      population. It affects quality of life (especially sleep) and lowers work
      efficiency. The aim of this document is to agree on how to treat NO, establish a
      methodology for evaluating and diagnosing it, and define an individualized
      approach to its treatment. NO can be unilateral or bilateral, intermittent or
      persistent and may be caused by local or systemic factors, which may be
      anatomical, inflammatory, neurological, hormonal, functional, environmental, or
      pharmacological in origin. Directed study of the medical history and physical
      examination are key for diagnosing the specific cause. NO may be evaluated using
      subjective assessment tools (visual analog scale, symptom score, standardized
      questionnaires) or by objective estimation (active anterior rhinomanometry,
      acoustic rhinometry, peak nasal inspiratory flow). Although there is little
      correlation between the results, they may be considered complementary and not
      exclusive. Assessing the impact on quality of life through questionnaires
      standardized according to the underlying disease is also advisable. NO is treated
      according to its cause. Treatment is fundamentally pharmacological (topical
      and/or systemic) when the etiology is inflammatory or functional. Surgery may be
      necessary when medical treatment fails to complement or improve medical treatment
      or when other therapeutic approaches are not possible. Combinations of surgical
      techniques and medical treatment may be necessary.

PMID- 29345623
TI  - Affordable and accurate large-scale hybrid-functional calculations on GPU
      accelerated supercomputers.
AB  - Performing high accuracy hybrid functional calculations for condensed matter
      systems containing a large number of atoms is at present computationally very
      demanding or even out of reach if high quality basis sets are used. We present a
      highly optimized multiple graphics processing unit implementation of the exact
      exchange operator which allows one to perform fast hybrid functional density
      functional theory (DFT) calculations with systematic basis sets without
      additional approximations for up to a thousand atoms. With this method hybrid DFT
      calculations of high quality become accessible on state-of-the-art supercomputers
      within a time-to-solution that is of the same order of magnitude as traditional
      semilocal-GGA functionals. The method is implemented in a portable open-source
      library.

PMID- 29345624
TI  - The role of H-bond in the high-pressure chemistry of model molecules.
AB  - Pressure is an extraordinary tool to modify direction and strength of
      intermolecular interactions with important consequences on the chemical stability
      of molecular materials. The decrease of the distance among nearest neighbour
      molecules can give rise to reactive configurations reflecting the crystal
      arrangement and leading to association processes. In this context, the role of
      the H-bonds is very peculiar because their usual strengthening with rising
      pressure does not necessarily configure a decrease of the reaction activation
      energy but, on the contrary, can give rise to an anomalous stability of the
      system. In spite of this central role, the mechanisms by which a chemical
      reaction is favoured or prevented by H-bonding under high pressure conditions is
      a poorly explored field. Here we review a few studies where the chemical
      behaviour of simple molecular systems under static compression was related to the
      H-bonding evolution with pressure. These results are able to clarify a wealth of
      changes of the chemical and physical properties caused by the strengthening with
      pressure of the H-bonding network and provide additional tools to understand the
      mechanisms of high-pressure reactivity, a mandatory step to make these synthetic
      methods of potential interest for applicative purposes.

PMID- 29345625
TI  - The all-optical modulator in dielectric-loaded waveguide with graphene-silicon
      heterojunction structure.
AB  - All-optical modulators based on graphene show great promise for on-chip optical
      interconnects. However, the modulation performance of all-optical modulators is
      usually based on the interaction between graphene and the fiber, limiting their
      potential in high integration. Based on this point, an all-optical modulator in a
      dielectric-loaded waveguide (DLW) with a graphene-silicon heterojunction
      structure (GSH) is proposed. The DLW raises the waveguide mode, which provides a
      strong light-graphene interaction. Sufficient tuning of the graphene Fermi energy
      beyond the Pauli blocking effect is obtained with the presented GSH structure.
      Under the modulation light with a wavelength of 532 nm and a power of 60 mW, a
      modulation efficiency of 0.0275 dB um-1 is achieved for light with a
      communication wavelength of 1.55 um in the experiment. This modulator has the
      advantage of having a compact footprint, which may make it a candidate for
      achieving a highly integrated all-optical modulator.

PMID- 29345626
TI  - Accelerating acquisition strategies for low-frequency conductivity imaging using
      MREIT.
AB  - We sought to improve efficiency of magnetic resonance electrical impedance
      tomography data acquisition so that fast conductivity changes or electric field
      variations could be monitored. Undersampling of k-space was used to decrease
      acquisition times in spin-echo-based sequences by a factor of two. Full MREIT
      data were reconstructed using continuity assumptions and preliminary scans
      gathered without current. We found that phase data were reconstructed faithfully
      from undersampled data. Conductivity reconstructions of phantom data were also
      possible. Therefore, undersampled k-space methods can potentially be used to
      accelerate MREIT acquisition. This method could be an advantage in imaging real
      time conductivity changes with MREIT.

PMID- 29345627
TI  - Large-area synthesis and photoelectric properties of few-layered MoSe<sub>2</sub>
      on molybdenum foils.
AB  - Compared with MoS2 and WS2, the selenide analogues have narrower band gaps and
      higher electron mobilities, which make them more applicable to real electrical
      devices. Besides, few-layered metal selenides have higher electrical
      conductivity, carrier mobility and light absorption than the corresponding
      monolayers. However, the large-scale and high-quality growth of few-layered metal
      selenides remains a significant challenge. Here, we develop a facile method to
      grow large-area and highly-crystalline few-layered MoSe2 by directly selenizing
      the Mo foil surfaces at 550 oC within 60 min under ambient pressure. The atomic
      layers were controllably grown with the thickness between 3.4 and 6 nm which just
      met the thickness range required for high-performance electrical devices.
      Furthermore, we fabricated a vertical p-n junction photodetector composed of few
      layered MoSe2 and p-type silicon, achieving photoresponsivity higher than two
      orders of magnitude than that of the reported monolayer counterpart. This
      technique provides a feasible approach towards preparing other 2D TMDs for device
      applications.

PMID- 29345628
TI  - Reversibility and intermediate steps as key tools for the growth of extended
      ordered polymers via on-surface synthesis.
AB  - Surface-confined polymerization is a bottom-up strategy to create one- and two
      dimensional covalent organic nanostructures with a pi-conjugated backbone, which
      are suitable to be employed in real-life electronic devices, due to their high
      mechanical resistance and electronic charge transport efficiency. This strategy
      makes it possible to change the properties of the final nanostructures by a
      careful choice of the monomer architecture (i.e. of its constituent atoms and
      their spatial arrangement). Several chemical reactions have been proven to form
      low-dimensional polymers on surfaces, exploiting a variety of precursors in
      combination with metal (e.g. Cu, Ag, Au) and insulating (e.g. NaCl, CaCO3)
      surfaces. One of the main challenges of such an approach is to obtain
      nanostructures with long-range order, to boost the conductance performances of
      these materials. Most of the exploited chemical reactions use irreversible
      coupling between the monomers and, as a consequence, the resulting structures
      often suffer from poor order and high defect density. This review focuses on the
      state-of-the-art surface-confined polymerization reactions, with particular
      attention paid to reversible coupling pathways and irreversible processes
      including intermediate states, which are key aspects to control to increase the
      order of the final nanostructure.

PMID- 29345629
TI  - Molecular dynamics based simulations to study the fracture strength of monolayer
      graphene oxide.
AB  - The aim of this article is to study the effects of functional groups such as
      hydroxyl, epoxide and carboxyl on the fracture toughness of graphene. These
      functional groups form the backbone of the intrinsic atomic structure of graphene
      oxide (GO). Molecular dynamics based simulations were performed in conjunction
      with reactive force field parameters to capture the Mode-I fracture toughness of
      functionalised graphene. Simulations were performed in stages, to study the
      effect of these functional groups, individually as well as all together on the
      fracture toughness of GO nanosheets. The molecular dynamics based simulations
      performed in this article helps us to conclude that the spatial distribution and
      concentration of functional groups significantly affects the fracture behavior of
      GO nanosheets.

PMID- 29345630
TI  - Completely flat two-dimensional Zn<sub>3</sub>O<sub>2</sub> monolayer with
      triangle and pentangle coordinated networks.
AB  - Two-dimensional (2D) materials with strictly planar hyper-coordinated motifs are
      of great importance in fundamental science and potential applications but
      extremely rare. Here we theoretically design a novel 2D IIB-VIA inorganic system,
      namely Zn3O2 monolayer, by comprehensive first-principles computations. This
      Zn3O2 monolayer is composed from highly symmetrical tri-coordinated oxygen and
      tetra-coordinated zinc, featuring planar and peculiar triangle and pentangle
      combined bonded network. The newly predicted Zn3O2 monolayer possesses excellent
      dynamic and thermal stabilities and is also the lowest-energy structure of its 2D
      space indicated by particle swarm search, supporting its experimentally synthetic
      viability. A relatively wide band gap of 4.46 eV endows it potential applications
      in electronics and optoelectronics. The present findings provide a new field of
      hyper-coordinated 2D nanomaterials for study.

PMID- 29345631
TI  - Role of four-fermion interaction and impurity in the states of two-dimensional
      semi-Dirac materials.
AB  - We study the effects of four-fermion interaction and impurity on the low-energy
      states of 2D semi-Dirac materials by virtue of the unbiased renormalization group
      approach. The coupled flow equations that govern the energy-dependent evolutions
      of all correlated interaction parameters are derived after taking into account
      one-loop corrections from the interplay between four-fermion interaction and
      impurity. Whether and how four-fermion interaction and impurity influence the low
      energy properties of 2D semi-Dirac materials are discreetly explored and
      addressed attentively. After carrying out the standard renormalization group
      analysis, we find that both trivial insulating and nontrivial semimetal states
      are qualitatively stable against all four kinds of four-fermion interactions.
      However, while switching on both four-fermion interaction and impurity, certain
      insulator-semimetal phase transitions and the distance of Dirac nodal points can
      be respectively induced and modified due to their strong interplay and intimate
      competition. Moreover, several non-Fermi liquid behaviors that deviate from the
      conventional Fermi liquids are exhibited at the lowest-energy limit.

PMID- 29345632
TI  - Brain-machine interfaces for controlling lower-limb powered robotic systems.
AB  - OBJECTIVE: Lower-limb, powered robotics systems such as exoskeletons and orthoses
      have emerged as novel robotic interventions to assist or rehabilitate people with
      walking disabilities. These devices are generally controlled by certain physical
      maneuvers, for example pressing buttons or shifting body weight. Although
      effective, these control schemes are not what humans naturally use. The usability
      and clinical relevance of these robotics systems could be further enhanced by
      brain-machine interfaces (BMIs). A number of preliminary studies have been
      published on this topic, but a systematic understanding of the experimental
      design, tasks, and performance of BMI-exoskeleton systems for restoration of gait
      is lacking. APPROACH: To address this gap, we applied standard systematic review
      methodology for a literature search in PubMed and EMBASE databases and identified
      11 studies involving BMI-robotics systems. The devices, user population, input
      and output of the BMIs and robot systems respectively, neural features, decoders,
      denoising techniques, and system performance were reviewed and compared. MAIN
      RESULTS: Results showed BMIs classifying walk versus stand tasks are the most
      common. The results also indicate that electroencephalography (EEG) is the only
      recording method for humans. Performance was not clearly presented in most of the
      studies. Several challenges were summarized, including EEG denoising, safety,
      responsiveness and others. SIGNIFICANCE: We conclude that lower-body powered
      exoskeletons with automated gait intention detection based on BMIs open new
      possibilities in the assistance and rehabilitation fields, although the current
      performance, clinical benefits and several key challenging issues indicate that
      additional research and development is required to deploy these systems in the
      clinic and at home. Moreover, rigorous EEG denoising techniques, suitable
      performance metrics, consistent trial reporting, and more clinical trials are
      needed to advance the field.

PMID- 29345633
TI  - Impacts of an Exercise Program and Motivational Telephone Counseling on Health
      Related Quality of Life in People With Parkinson's Disease.
AB  - PURPOSE: The purpose of this study was to test the effects of group exercise and
      telephone counseling on physical and psychosocial health in people with
      Parkinson's disease (PD). DESIGN: This was a quasiexperimental study with a
      nonequivalent control group. METHODS: This study took place in Seoul, South
      Korea. Twenty-two and 20 subjects participated in the intervention and comparison
      groups, respectively. The intervention group performed group exercises twice a
      week and received motivational telephone counseling every 2 weeks for 12 weeks.
      FINDINGS: Significant effects of the intervention were found in overall health
      related quality of life (HRQOL; p = .012) and in the following HRQOL dimensions:
      stigma (p = .026), social function (p = .003), cognition (p = .028), and
      communication (p = .014). No other variables such as activities of daily living,
      functional fitness, and depression exhibited statistically significant effects.
      CONCLUSION/CLINICAL RELEVANCE: These results indicate that group exercise with
      telephone counseling positively affects some aspects of HRQOL in PD patients.

PMID- 29345634
TI  - Erratum.

PMID- 29345635
TI  - Genetic risk, dysbiosis, and treatment stratification using host genome and gut
      microbiome in inflammatory bowel disease.
AB  - OBJECTIVES: Inflammatory bowel diseases (IBD), comprised of Crohn's disease (CD)
      and ulcerative colitis (UC), are characterized by a complex pathophysiology that
      is thought to result from an aberrant immune response to a dysbiotic luminal
      microbiota in genetically susceptible individuals. New technologies support the
      joint assessment of host-microbiome interaction. METHODS: Using whole genome
      sequencing and shotgun metagenomics, we studied the clinical features, host
      genome, and stool microbial metagenome of 85 IBD patients, and compared the
      results to 146 control individuals. Genetic risk scores, computed on 159 single
      nucleotide variants, and human leukocyte antigen (HLA) types differentiated IBD
      patients from healthy controls. RESULTS: Genetic risk was associated with the
      need for use of biologics in IBD and, modestly, with the composition of the gut
      microbiome. As compared with healthy controls, IBD patients had hallmarks of
      stool microbiome dysbiosis, with loss of a diversified core microbiome,
      enrichment and depletion of specific bacteria, and enrichment of bacterial
      virulence factors. CONCLUSIONS: We show that genetic risk may have a role in
      early risk stratification in the care of IBD patients and propose that expression
      of virulence factors in a dysbiotic microbiome may contribute to pathogenesis in
      IBD.

PMID- 29345637
TI  - Structural basis of RNA polymerase III transcription initiation.
AB  - RNA polymerase (Pol) III transcribes essential non-coding RNAs, including the
      entire pool of transfer RNAs, the 5S ribosomal RNA and the U6 spliceosomal RNA,
      and is often deregulated in cancer cells. The initiation of gene transcription by
      Pol III requires the activity of the transcription factor TFIIIB to form a
      transcriptionally active Pol III preinitiation complex (PIC). Here we present
      electron microscopy reconstructions of Pol III PICs at 3.4-4.0 A and a
      reconstruction of unbound apo-Pol III at 3.1 A. TFIIIB fully encircles the DNA
      and restructures Pol III. In particular, binding of the TFIIIB subunit Bdp1
      rearranges the Pol III-specific subunits C37 and C34, thereby promoting DNA
      opening. The unwound DNA directly contacts both sides of the Pol III cleft.
      Topologically, the Pol III PIC resembles the Pol II PIC, whereas the Pol I PIC is
      more divergent. The structures presented unravel the molecular mechanisms
      underlying the first steps of Pol III transcription and also the general
      conserved mechanisms of gene transcription initiation.

PMID- 29345636
TI  - Promoting the accumulation of tumor-specific T cells in tumor tissues by
      dendritic cell vaccines and chemokine-modulating agents.
AB  - This protocol describes how to induce large numbers of tumor-specific cytotoxic T
      cells (CTLs) in the spleens and lymph nodes of mice receiving dendritic cell (DC)
      vaccines and how to modulate tumor microenvironments (TMEs) to ensure effective
      homing of the vaccination-induced CTLs to tumor tissues. We also describe how to
      evaluate the numbers of tumor-specific CTLs within tumors. The protocol contains
      detailed information describing how to generate a specialized DC vaccine with
      augmented ability to induce tumor-specific CTLs. We also describe methods to
      modulate the production of chemokines in the TME and show how to quantify tumor
      specific CTLs in the lymphoid organs and tumor tissues of mice receiving
      different treatments. The combined experimental procedure, including tumor
      implantation, DC vaccine generation, chemokine-modulating (CKM) approaches, and
      the analyses of tumor-specific systemic and intratumoral immunity is performed
      over 30-40 d. The presented ELISpot-based ex vivo CTL assay takes 6 h to set up
      and 5 h to develop. In contrast to other methods of evaluating tumor-specific
      immunity in tumor tissues, our approach allows detection of intratumoral T-cell
      responses to nonmanipulated weakly immunogenic cancers. This detection method can
      be performed using basic laboratory skills, and facilitates the development and
      preclinical evaluation of new immunotherapies.

PMID- 29345638
TI  - Molecular mechanism of promoter opening by RNA polymerase III.
AB  - RNA polymerase III (Pol III) and transcription factor IIIB (TFIIIB) assemble
      together on different promoter types to initiate the transcription of small,
      structured RNAs. Here we present structures of Pol III preinitiation complexes,
      comprising the 17-subunit Pol III and the heterotrimeric transcription factor
      TFIIIB, bound to a natural promoter in different functional states. Electron cryo
      microscopy reconstructions, varying from 3.7 A to 5.5 A resolution, include two
      early intermediates in which the DNA duplex is closed, an open DNA complex, and
      an initially transcribing complex with RNA in the active site. Our structures
      reveal an extremely tight, multivalent interaction between TFIIIB and promoter
      DNA, and explain how TFIIIB recruits Pol III. Together, TFIIIB and Pol III
      subunit C37 activate the intrinsic transcription factor-like activity of the Pol
      III-specific heterotrimer to initiate the melting of double-stranded DNA, in a
      mechanism similar to that of the Pol II system.

PMID- 29345640
TI  - Strategy for making safer opioids bolstered.

PMID- 29345639
TI  - Emergent constraint on equilibrium climate sensitivity from global temperature
      variability.
AB  - Equilibrium climate sensitivity (ECS) remains one of the most important unknowns
      in climate change science. ECS is defined as the global mean warming that would
      occur if the atmospheric carbon dioxide (CO2) concentration were instantly
      doubled and the climate were then brought to equilibrium with that new level of
      CO2. Despite its rather idealized definition, ECS has continuing relevance for
      international climate change agreements, which are often framed in terms of
      stabilization of global warming relative to the pre-industrial climate. However,
      the 'likely' range of ECS as stated by the Intergovernmental Panel on Climate
      Change (IPCC) has remained at 1.5-4.5 degrees Celsius for more than 25 years. The
      possibility of a value of ECS towards the upper end of this range reduces the
      feasibility of avoiding 2 degrees Celsius of global warming, as required by the
      Paris Agreement. Here we present a new emergent constraint on ECS that yields a
      central estimate of 2.8 degrees Celsius with 66 per cent confidence limits
      (equivalent to the IPCC 'likely' range) of 2.2-3.4 degrees Celsius. Our approach
      is to focus on the variability of temperature about long-term historical warming,
      rather than on the warming trend itself. We use an ensemble of climate models to
      define an emergent relationship between ECS and a theoretically informed metric
      of global temperature variability. This metric of variability can also be
      calculated from observational records of global warming, which enables tighter
      constraints to be placed on ECS, reducing the probability of ECS being less than
      1.5 degrees Celsius to less than 3 per cent, and the probability of ECS exceeding
      4.5 degrees Celsius to less than 1 per cent.

PMID- 29345642
TI  - Support for US postdocs is growing slowly.

PMID- 29345641
TI  - The dark side of light: how artificial lighting is harming the natural world.

PMID- 29345644
TI  - China's plan to recruit talented researchers.

PMID- 29345645
TI  - Integrity must underpin quality of statistics.

PMID- 29345646
TI  - Scientists in China regenerate lens in human eye.

PMID- 29345647
TI  - Laws are not the only way to boost immunization.

PMID- 29345648
TI  - Fossilized pregnant dinosaur discovered in southern China.

PMID- 29345649
TI  - NASA test proves pulsars can function as a celestial GPS.

PMID- 29345650
TI  - Synthetic species made to shun sex with wild organisms.

PMID- 29345651
TI  - US i mmigration fight heightens legal limbo for young 'Dreamer' scientists.

PMID- 29345652
TI  - Revamped collider hunts for cracks in the fundamental theory of physics.

PMID- 29345653
TI  - Make lighting healthier.

PMID- 29345655
TI  - China enters the battle for AI talent.

PMID- 29345654
TI  - Ben Barres (1954-2017).

PMID- 29345656
TI  - Intelligence conference, rainforest park and oil-spill fears.

PMID- 29345657
TI  - Putting China's science on the map.

PMID- 29345658
TI  - How a biotech entrepreneur benefits from splitting time between China and the
      United States.

PMID- 29345659
TI  - Returning to a revitalized China after research abroad.

PMID- 29345660
TI  - Pathogens boosted by food additive.

PMID- 29345661
TI  - How private-sector research is changing China.

PMID- 29345662
TI  - Maths strikes a blow for democracy.

PMID- 29345663
TI  - Don't misrepresent link between bats and SARS.

PMID- 29345664
TI  - Could baby's first bacteria take root before birth?

PMID- 29345665
TI  - How to find a job in China.

PMID- 29345666
TI  - Limitless translation limits translation.

PMID- 29345667
TI  - Showcase scientists from the global south.

PMID- 29345668
TI  - The ups and downs of moving to China.

PMID- 29345669
TI  - Why China needs your scientific expertise.

PMID- 29345671
TI  - Why an Italian astrophysicist decided to move to Shanghai.

PMID- 29345672
TI  - Train robots to self-certify their safe operation.

PMID- 29345673
TI  - China's AI dreams.

PMID- 29345675
TI  - The Fields Medal should return to its roots.

PMID- 29345674
TI  - Career guide: China.

PMID- 29345677
TI  - Mice learn to avoid the rat race.

PMID- 29345676
TI  - Research kudos does not need a price tag.

PMID- 29345679
TI  - Fixing statistics is more than a technical issue.

PMID- 29345680
TI  - Should we steer clear of the winner-takes-all approach?

PMID- 29345678
TI  - China needs to listen to its researchers to become a scientific superpower.

PMID- 29345681
TI  - Biotech booms in China.

PMID- 29345683
TI  - Homing in on a key factor of climate change.

PMID- 29345684
TI  - MSH6 and PMS2 germ-line pathogenic variants implicated in Lynch syndrome are
      associated with breast cancer.
AB  - PURPOSE: An association of Lynch syndrome (LS) with breast cancer has been long
      suspected; however, there have been insufficient data to address this question
      for each of the LS genes individually. METHODS: We conducted a retrospective
      review of personal and family history in 423 women with pathogenic or likely
      pathogenic germ-line variants in MLH1 (N = 65), MSH2 (N = 94), MSH6 (N = 140), or
      PMS2 (N = 124) identified via clinical multigene hereditary cancer testing.
      Standard incidence ratios (SIRs) of breast cancer were calculated by comparing
      breast cancer frequencies in our study population with those in the general
      population (Surveillance, Epidemiology, and End Results 18 data). RESULTS: When
      evaluating by gene, the age-standardized breast cancer risks for MSH6 (SIR =
      2.11; 95% confidence interval (CI), 1.56-2.86) and PMS2 (SIR = 2.92; 95% CI, 2.17
      3.92) were associated with a statistically significant risk for breast cancer
      whereas no association was observed for MLH1 (SIR = 0.87; 95% CI, 0.42-1.83) or
      MSH2 (SIR = 1.22; 95% CI, 0.72-2.06). CONCLUSION: Our data demonstrate that two
      LS genes, MSH6 and PMS2, are associated with an increased risk for breast cancer
      and should be considered when ordering genetic testing for individuals who have a
      personal and/or family history of breast cancer.

PMID- 29345685
TI  - Imaging: Pacemakers, ICDs, and MRI.

PMID- 29345687
TI  - Interventional cardiology: 3D printing of personalized implants for left atrial
      appendage occlusion.

PMID- 29345686
TI  - Reversal agents for non-vitamin K antagonist oral anticoagulants.
AB  - The non-vitamin K antagonist oral anticoagulants (NOACs) include dabigatran,
      which inhibits thrombin, and apixaban, betrixaban, edoxaban, and rivaroxaban,
      which inhibit coagulation factor Xa. Although clinical studies of NOACs were
      conducted without antidotes, patient outcomes with major bleeding when receiving
      NOACs were no worse than those in patients treated with a vitamin K antagonist.
      Nonetheless, in patients with life-threatening bleeding or requiring urgent
      surgery, the capacity for rapid NOAC reversal is likely to increase patient
      safety. Three NOAC reversal agents are in various stages of development:
      idarucizumab, a specific reversal agent for dabigatran; andexanet alfa, which
      reverses factor Xa inhibitors; and ciraparantag, which is purported to reverse
      all NOACs. Idarucizumab is licensed in many countries, andexanet is under
      consideration by regulatory agencies, and ciraparantag is undergoing phase III
      evaluation. In the absence of licensed reversal agents for the oral factor Xa
      inhibitors, prothrombin complex concentrates are often used in patients taking
      these agents who present with life-threatening bleeding. In this Review, we
      summarize the approved indications for the NOACs, outline how to measure their
      anticoagulant effects, describe the mechanism of action of the reversal
      strategies, assess the preclinical and clinical data supporting their use,
      provide guidance on potential indications for reversal, and offer a management
      approach for patients treated with NOACs who present with serious bleeding or
      require urgent surgery.

PMID- 29345688
TI  - Corrigendum.
AB  - [This corrects the article DOI: 10.1177/1757177417695647.].

PMID- 29345689
TI  - Concerns with conclusions in the article by Sherwood et al 'Key differences
      between 13 KRAS mutation detection technologies and their relevance for clinical
      practice'.

PMID- 29345690
TI  - Clozapine-induced myocarditis.
AB  - Approved in 1989 for the management of treatment-resistant schizophrenia,
      Clozapine is a last-line atypical antipsychotic drug used with increasing
      frequency. In addition to its well-known side effect of agranulocytosis, this
      drug also carries with it rare but serious adverse cardiovascular risk of
      myocarditis. We present a patient on Clozapine who was admitted to the cardiology
      service with chest pain, ST segment elevations and elevated troponin concerning
      for acute myocardial infarction. Evaluation with imaging revealed decreased left
      ventricular function, however, no coronary artery disease was present on
      catheterization; findings consistent with a diagnosis of myocarditis. Subsequent
      discontinuation of the patient's Clozapine and initiation of brief supportive
      medical therapy resulted in full recovery of systolic left ventricular function.
      Given the potential cardiovascular mortality risk, it is important for physicians
      on cardiology services caring for psychiatric patients to be aware of the
      presentation of symptoms, diagnostic findings and management of Clozapine induced
      myocarditis.

PMID- 29345691
TI  - Re: Goel A. Research training during residency. Indian J Urol 2017;33:257-8.

PMID- 29345693
TI  - Corrigendum.
AB  - [This corrects the article DOI: 10.1177/1757177417720999.].

PMID- 29345692
TI  - Erratum: Publisher's Note: "Implications of short time scale dynamics on long
      time processes" (Struct. Dyn. 4, 061507 (2017)].
AB  - [This corrects the article DOI: 10.1063/1.4996448.].

PMID- 29345694
TI  - Erratum to: Physical fitness of Ghanaian physiotherapists and its correlation
      with age and exercise engagement: a pilot study.
AB  - [This corrects the article DOI: 10.1186/s40945-016-0016-2.].

PMID- 29345695
TI  - Erratum: Kini Bailur J, Mehta S, Zhang L, et al. Changes in bone marrow innate
      lymphoid cell subsets in monoclonal gammopathy: target for IMiD therapy. Blood
      Adv. 2017;1(25):2343-2347.
AB  - [This corrects the article DOI: 10.1182/bloodadvances.2017012732.].

PMID- 29345697
TI  - Re: Singh A et al. Robot-assisted retroperitoneal lymph node dissection:
      Feasibility and outcome in postchemotherapy residual mass in testicular cancer.
      Indian J Urol 2017;33:304-9.

PMID- 29345696
TI  - Antiemetic efficacy and safety of granisetron or palonosetron alone and in
      combination with a corticosteroid for ABVD therapy-induced nausea and vomiting.
AB  - Background: Antiemetic effects and safety of granisetron or palonosetron alone
      and in combination with a corticosteroid against chemotherapy-induced nausea and
      vomiting (CINV) were retrospectively evaluated in patients with Hodgkin lymphoma
      receiving adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) therapy.
      Methods: A total of 39 patients were eligible for this study. Before ABVD
      therapy, granisetron or palonosetron was intravenously administered with or
      without a corticosteroid (dexamethasone or hydrocortisone) and aprepitant. The
      proportions of patients with complete control (CC) during the overall (0-120 h
      after the start of ABVD therapy), acute (0-24 h) and delayed (24-120 h) phases
      were evaluated. CC was defined as no vomiting and no use of antiemetic rescue
      medication with only grade 0-1 nausea. Results: Granisetron and palonosetron were
      administered in 21 and 18 patients, respectively. The CC rate during the acute,
      delayed and overall phases was not statistically different between the two
      groups. The CINV was completely controlled during overall phase in 58.3% of
      patients receiving granisetron or palonosetron in combination with a
      corticosteroid, whereas in 11.1% of those without co-treatment of a
      corticosteroid (P < 0.05). There were significantly higher frequencies of
      anorexia, leucopenia and neutropenia in the palonosetron group. There is a
      statistically significant difference in the frequency of febrile neutropenia
      between presence and absence of a corticosteroid (p = 0.024). Conclusion: These
      findings suggested that a combination use of a corticosteroid with a 5-HT3
      receptor antagonist was preferable for CINV control in patients with Hodgkin
      lymphoma receiving ABVD therapy, although the careful management of febrile
      neutropenia is required. Trial registration: The study approval numbers in the
      institution; 24-12 and 24-359. Registered April 17, 2012 and June 21, 2012.

PMID- 29345698
TI  - Aerogen bonds formed between AeOF2 (Ae = Kr, Xe) and diazines: comparisons
      between sigma-hole and pi-hole complexes.
AB  - The interaction between KrOF2 or XeOF2 and the 1,2, 1,3, and 1,4 diazines is
      characterized chiefly by a Kr/XeN aerogen bond, as deduced from ab initio
      calculations. The most stable dimers take advantage of the sigma-hole on the
      aerogen atom, wherein the two molecules lie in the same plane. The interaction is
      quite strong, as much as 18 kcal mol-1. A second class of dimer geometry utilizes
      the pi-hole above the aerogen atom in an approximate perpendicular arrangement of
      the two monomers; these structures are not as strongly bound: 6-8 kcal mol-1.
      Both sorts of dimers contain auxiliary CHF H-bonds which contribute to their
      stability, but even with their removal, the aerogen bond energy remains as high
      as 14 kcal mol-1. The nature and strength of each specific interaction is
      confirmed and quantified by AIM, NCI, NBO, and electron density shift patterns.
      There is not a great deal of sensitivity to the identity of either the aerogen
      atom or the position of the two N atoms in the diazine.

PMID- 29345699
TI  - Theoretical investigations on the unsymmetrical effect of beta-link Zn-porphyrin
      sensitizers on the performance for dye-sensitized solar cells.
AB  - Dye sensitizers play an important role in dye-sensitized solar cells (DSSCs). As
      a promising strategy for the design of novel porphyrin sensitizers, the
      asymmetric modification of the porphyrin ring to meso-link porphyrin sensitizer
      has emerged in recent years, which can improve the light-harvesting properties
      and enhance the electron distribution. In this work, in order to reveal the
      essence of the effect of unsymmetrical substitution on the performance of beta
      link porphyrin dyes in DSSCs, four kinds of common beta-link porphyrin dyes with
      different structures are calculated by using density functional theory (DFT) and
      time-dependent density functional theory (TD-DFT). The electronic structures and
      optical properties of these studied dyes in dimethylformamide (DMF) are also
      investigated. The key parameters of the short-circuit current density (Jsc),
      including light harvesting efficiency (LHE), electron injection driving force
      (DeltaGinject), and intra-molecular charge transfer (ICT) are discussed in
      detail. In addition, the periodic DFT calculations in the dye-TiO2 systems are
      also employed to investigate the geometrical and electronic injection process of
      the different connection types of these studied dyes adsorbed on the periodic
      TiO2 model with an exposed anatase (101) surface. We expect the present study
      would deepen the understanding of the alternative function of unsymmetrical
      substitution and may contribute to future DSSC design.

PMID- 29345700
TI  - Abnormal separation of the silicon-oxygen bond in the liquid layering transition
      of silicon dioxide in a nanoslit.
AB  - We investigated the unusual layering transition (LT) in quasi-2D liquid silicon
      dioxide (SiO2) confined in a nanoslit. Our results indicate that the slit size
      and pressure induce the abnormal LT in liquid SiO2, accompanied by a rapid change
      in the density, diffusion coefficient, pair correlation function and average
      potential energy. The silicon and oxygen atoms are almost completely separated
      under the extremely strong confinement effect, which is the characteristic
      feature of the LT. The negative slope of the LT lines in the phase diagram at
      different pressures suggests that a confinement-induced LT occurs at high
      pressure and a pressure-induced LT occurs at low pressure.

PMID- 29345701
TI  - Effects of particle size and annealing on plasmon-induced charge separation at
      self-assembled gold nanoparticle arrays.
AB  - Two-dimensional periodic Au nanoparticle arrays were constructed on TiO2 thin
      films by a micelle lithography method and seed-mediated photoelectrochemical
      growth. Their adjustable interparticle distance allows investigation of a
      particle size effect on plasmon-induced charge separation (PICS) efficiencies
      without interference from particle aggregation or plasmon coupling. External or
      internal PICS efficiencies were found to increase and decrease, respectively,
      with an increase in particle diameter from 25 to 38 nm. Improvement of the
      contact between Au nanoparticles and TiO2 by annealing enhanced the intensity of
      a plasmonic interface mode and both external and internal PICS efficiencies.

PMID- 29345702
TI  - Assessing the consumption of berries and associated factors in the United States
      using the National Health and Nutrition Examination Survey (NHANES), 2007-2012.
AB  - Intake of berries was assessed relative to other fruit and fruit juices and total
      fruit intake in the U.S. population age 2 years and older using the National
      Health and Nutrition Examination Survey, 2007-2012. Average daily intake of total
      fruit was about 1 cup, and berries comprised approximately 10% of total fruit
      consumption. Only 18% of the population met the recommendation of at least 2 cups
      of fruit per day. Children ages 2 to 5 years consumed the most total fruit of
      which about half was juice and 4% of which was berries. Among adults, the highest
      berry consumption was by those who were 65 years and older, non-Hispanic White,
      and had the highest education and income levels. Use of the Nutrition Facts panel
      and ingredient labeling was associated with greater total fruit and berry intake.
      Those who were aware of an amount of fruit that is associated with good health
      and of dietary guidance in general and those who had fruit available in the home
      consumed about twice as much berries as others. Fruit intake remains below
      recommendations in the U.S.; berry intake is particularly low. Behavioral
      indicators provided insight on how fruit and berry consumption might be
      increased.

PMID- 29345703
TI  - Controllable colloidal synthesis of anisotropic tin dichalcogenide nanocrystals
      for thin film thermoelectrics.
AB  - Tin chalcogenides have shown promise in applications including energy storage,
      optoelectronics, photovoltaics, and thermoelectrics. Here, we present a colloidal
      synthesis strategy to produce tin dichalcogenide nanocrystals (NCs) with
      controllable stoichiometry, vacancies, shape, and crystal structure. Compared
      with previously reported methods, we use less expensive precursors, such as
      tin(iv) chloride and sulfur or selenium powder, to produce tin(iv) chalcogenide
      NCs. SnS2 and SnSe2 NCs with novel NC morphologies including SnS2
      nanoflowers/nanoflakes, SnSe2 nanosheets with circular and hexagonal shapes, as
      well as mixtures of nanospheres and nanoflakes were prepared by varying the
      solvents and anion precursors. We were also able to reduce tin(iv) to tin(ii) to
      produce tin(ii) chalcogenide NCs. The corresponding thin films were prepared by
      spin-coating, followed by post-treatment to study their thermoelectric
      properties. Room temperature Seebeck coefficients of -150 MUV K-1 and -126 MUV K
      1 were measured for SnS2 and SnSe2 films, demonstrating their promise as thin
      film thermoelectric materials.

PMID- 29345704
TI  - Hierarchical core-shell structures of P-Ni(OH)2 rods@MnO2 nanosheets as high
      performance cathode materials for asymmetric supercapacitors.
AB  - The hierarchical porous structure with phosphorus-doped Ni(OH)2 (P-Ni(OH)2) rods
      as the core and MnO2 nanosheets as the shell is fabricated directly by growth on
      a three-dimensional (3D) flexible Ni foam (NF) via a two-step hydrothermal
      process. As a binder-free electrode material, this unique hybrid structure
      exhibits excellent electrochemical properties, including an ultrahigh areal
      capacitance of 5.75 F cm-2 at a current density of 2 mA cm-2 and great cyclic
      stability without capacitance loss at a current density of 20 mA cm-2 after 10
      000 cycles. Moreover, an all-solid-state asymmetric supercapacitor (AAS) based on
      a P-Ni(OH)2@MnO2 hybrid structure on Ni foam as the cathode and activated carbon
      (AC) as the anode is successfully assembled to enhance value the electrochemical
      properties. The AAS device also shows excellent electrochemical properties
      including a large potential window of 0~1.6 V, an areal capacitance is 911.3 mF
      cm-2 at a current density of 1 mA cm-2 and long-term cycling performance.
      Meanwhile, the AAS device also delivers a high energy density of 0.324 mW h cm-2
      at a power density of 0.8 mW cm-2; and can easily light colorful light-emitting
      diode (LED) lights, suggesting that 3D P-Ni(OH)2@MnO2 hybrid composite has
      promising potential for practical use in high-performance supercapacitors.

PMID- 29345705
TI  - Contact mechanics for polydimethylsiloxane: from liquid to solid.
AB  - Adhesion between a glass ball and a polydimethylsiloxane (PDMS) sample is
      dependent on the PDMS cross-link density, and the transformation of the material
      from the uncrosslinked liquid state to the fully crosslinked solid state is
      investigated in this study. The physical picture reflected a gradual transition
      from capillary forces driven contact mechanics to the classical Johnson-Kendall
      Roberts (JKR)-type contact mechanics. PDMS was produced by mixing the base fluid
      and a cross-linker at a ratio of 10 : 1 and allowed to slowly cross-link at room
      temperature with simultaneous measurement of the ball-PDMS interaction force. The
      PDMS sample was in the liquid state during the first ~16 hours, and in this case
      the ball-PDMS interaction was purely adhesive, i.e., no repulsive interaction was
      observed. Later at the PDMS gel-point the cross-linked PDMS clusters percolate,
      converting the fluid into a soft (fluid-filled) poroelastic solid. In the
      transition period, PDMS appears similar to pressure-sensitive adhesives. There we
      observe so-called "stringing" and permanent deformation of the material impacted
      by the ball. At room temperature, it takes more than ~100 hours for PDMS to fully
      cross-link that can be confirmed by the comparison with the earlier-studied
      reference PDMS produced at elevated temperatures.

PMID- 29345706
TI  - Tuning the nucleophilicity of electron-rich diborane(4) compounds with bridging
      guanidinate substituents by substitution.
AB  - Diborane(4) compounds are versatile reagents in synthetic chemistry. Generally,
      diboranes(4) with sp2-hybridized boron atoms react as electrophiles. By contrast,
      the chemistry of nucleophilic diborane(4) compounds with two sp3-hybridized boron
      atoms is very much underdeveloped. In this work, we systematically vary the
      substituents of electron-rich diborane(4) compounds with bridging guanidinate
      substituents. In this way, five new diboranes are synthesized and fully
      characterized. Using quantum chemical computations, we show that the electronic
      properties and reactivity of these compounds can be rationally varied by the
      choice of substituents. The HOMO energies, adiabatic ionization energies and
      proton affinities are considered as parameters to compare the chemical properties
      of these unusual compounds.

PMID- 29345709
TI  - Chain conformation of poly(acrylic acid)-graft-poly(ethylene oxide)-graft-dodecyl
      in solution: an anomalous counter-ions condensation.
AB  - A dielectric spectroscopy study on a polyelectrolyte in aqueous solutions, which
      contains hydrophobic groups in part of the side chains poly(acrylic acid)-graft
      poly(ethylene oxide)-graft-dodecyl (PAA-g-PEO-g-dodecyl) is reported. A refined
      double layer polarization model was proposed to analyze the double dielectric
      relaxations in the dielectric spectra. Various electrical and structural
      parameters of the copolymers were obtained. Besides the crossover concentration,
      another turning point around 4 mg mL-1 was identified through the analysis of all
      the dielectrical parameters including dielectric increment, relaxation time and
      correlation length. According to the scaling relationship between the correlation
      length and concentration, a necklace-like structure was predicted. In addition, 4
      mg mL-1 was proven to be the transition point between string-controlling with
      bead-controlling structure of the chains. In addition, the fraction of effective
      charges on the chains was illustrated by Ito's counter-ions fluctuation theory,
      as well as its linear dependence relationship with the zeta potential. Meanwhile,
      the counter-ions condensation behavior was consistent with the avalanche-like
      trend, which was predicted by theory for a hydrophobic polyelectrolyte with a
      necklace conformation. The results demonstrated that the electrostatic
      interactions were the main driving force of the necklace-like structure with
      pendant globules when the string-controlling structure was below 4 mg mL-1. While
      hydrophobic interactions are the main driving force of the structure of bead
      controlling above 4 mg mL-1.

PMID- 29345707
TI  - Synthesis and characterization of a photocleavable collagen-like peptide.
AB  - A 34-amino acid long collagen-like peptide rich in proline, hydroxyproline, and
      glycine, and with four photoreactive N-acyl-7-nitroindoline units incorporated
      into the peptide backbone was synthesized by on-resin fragment condensation. Its
      circular dichroism supports a stable triple helix structure. The built-in
      photochemical function enables the decomposition of the peptide into small
      peptide fragments by illumination with UV light of 350 nm in aqueous solution.
      Illumination of a thin film of the peptide, or a thin film of a photoreactive
      amino acid model compound containing a 5-bromo-7-nitroindoline moiety, with
      femtosecond laser light at 710 nm allows for the creation of well-resolved
      micropatterns. The cytocompatibility of the peptide was demonstrated using human
      mesenchymal stem cells and mouse embryonic fibroblasts. Our data show that the
      full-length peptide is cytocompatible as it can support cell growth and maintain
      cell viability. In contrast, the small peptide fragments created by photolysis
      are somewhat cytotoxic and therefore less cytocompatible. These data suggest that
      biomimetic collagen-like photoreactive peptides could potentially be used for
      growing cells in 2D micropatterns based on patterns generated by photolysis prior
      to cell growth.

PMID- 29345708
TI  - Triphenylstannyl((arylimino)methyl)benzoates with selective potency that induce
      G1 and G2/M cell cycle arrest and trigger apoptosis via ROS in human cervical
      cancer cells.
AB  - Metal complexes with organelle specificity and potent but selective cytotoxicity
      are highly desirable. A novel series of triphenylstannyl 4
      ((arylimino)methyl)benzoates (2-8) were obtained by the reactions of
      triphenylstannyl 4-formylbenzoate [Ph3Sn(L1)] 1 with primary aromatic amines. Two
      representative compounds (10, 11) were also synthesized by reacting aqua
      triphenylstannyl 2-formylbenzoate [Ph3Sn(L9)(H2O)] (9) with aniline and p
      fluoroaniline, respectively. These compounds were characterized by elemental
      analysis, IR and 1H, 13C and 119Sn NMR spectroscopy, as well as single-crystal X
      ray diffraction for compounds 5, 7-11 and three pro-ligands. The in vitro
      cytotoxic activities of 1-11 were assessed using the MTT tetrazolium dye assay
      against HeLa (human cervical) and MDA-MB-231 (breast) cancer cells, with IC50
      values revealing high activity. Compared to cisplatin, compounds 1-11 exhibited
      enhanced cytotoxic efficacy, indicating their potential as potent anticancer
      agents. Among these, 1 and 5 demonstrated maximum inhibition in HeLa cells, with
      negligible effect on normal human embryonic kidney (HEK) cells. The combined
      results of the DCFH-DA dye and Hoechst 33342/PI nuclear staining assays, along
      with flow cytometry analysis, show that they possess a dual mode of action: They
      induced apoptotic cell death, attributable to the tin-assisted generation of
      reactive oxygen species. Cell cycle analyses indicated that compounds 1 and 5
      exhibit cell growth inhibition and may cause turbulences in the G1 and G2/M
      phases.

PMID- 29345710
TI  - Small degree of anisotropic wetting on self-similar hierarchical wrinkled
      surfaces.
AB  - We studied the wetting behavior of multiscale self-similar hierarchical wrinkled
      surfaces. The hierarchical surface was fabricated on poly(dimethylsiloxane)
      (PDMS) substrates by manipulating the sequential strain release and combined
      plasma/ultraviolet ozone (UVO) treatment. The generated structured surface shows
      an independently controlled dual-scale roughness with level-1 small-wavelength
      wrinkles (wavelength of 700-1500 nm and amplitude of 50-500 nm) resting on level
      2 large-wavelength wrinkles (wavelength of 15-35 MUm and amplitude of 3.5-5 MUm),
      as well as accompanying orthogonal cracks. By tuning the aspect ratio of
      hierarchical wrinkles, the degree of wetting anisotropy in hierarchical wrinkled
      surfaces, defined as the contact angle difference between the parallel and
      perpendicular directions to the wrinkle grooves, is found to change between 3
      degrees  and 9 degrees . Through both experimental characterization (confocal
      fluorescence imaging) and theoretical analyses, we showed that the wetting state
      in the hierarchical wrinkled surface is in the Wenzel wetting state. We found
      that the measured apparent contact angle is larger than the theoretically
      predicted Wenzel contact angle, which is found to be attributed to the three
      phase contact line pinning effect of both wrinkles and cracks that generates
      energetic barriers during the contact line motion. This is evidenced by the
      observed sudden drop of over 20 degrees  in the static contact angles along both
      perpendicular and parallel directions after slight vibration perturbation.
      Finally, we concluded that the observed small degree of wetting anisotropy in the
      hierarchical wrinkled surfaces mainly arises from the competition between
      orthogonal wrinkles and cracks in the contact line pinning.

PMID- 29345711
TI  - Direct access to spirobiisoxazoline via the double 1,3-dipolar cycloaddition of
      nitrile oxide with allenoate.
AB  - The double [3 + 2]-cycloadditions between nitrile oxides and allenoates have been
      achieved. In the presence of DABCO combined with Et3N, 2-substituted buta-2,3
      dienoates reacted with oxime chlorides to afford spirobiisoxazolines in 55-90%
      yields via the double 1,3-dipolar cycloaddition. Notably, the construction of
      double isoxazoline moieties and two chiral centers including a spiro carbon
      center was achieved.

PMID- 29345712
TI  - The thiolation of pentafluorobenzene with disulfides by C-H, C-F bond activation
      and C-S bond formation.
AB  - A metal-free thiolation reaction between pentafluorobenzene and disulfides by C
      H, C-F bond activation and C-S bond formation is reported. Bisthiolated
      tetrafluorobenzene derivatives would be prepared in moderate to good yields from
      pentafluorobenzene and disulfides under mild conditions. A possible mechanism for
      the reaction was given.

PMID- 29345713
TI  - Synthetic and immunological studies on trimeric MUC1 immunodominant motif antigen
      based anti-cancer vaccine candidates.
AB  - Therapeutic vaccines have been regarded as a very promising treatment modality
      against cancer. Tumor-associated MUC1 is a promising antigen for the design of
      antitumor vaccines. However, body's immune tolerance and low immunogenicity of
      MUC1 glycopeptides limited their use as effective antigen epitopes of therapeutic
      vaccines. To solve this problem, we chose the immune dominant region of MUC1
      VNTRs. We designed and synthesized its linear trivalent glycopeptide fragments
      and coupled the fragments with BSA. Immunological evaluation indicated that the
      antibodies induced by glycosylated MUC1 based vaccine 11 had a stronger binding
      than non-glycosylated 10. The novel constructed antigen epitopes have the
      potential to overcome the weak immunogenicity of natural MUC1 glycopeptides and
      deserve further research.

PMID- 29345714
TI  - From discrete to continuous description of spherical surface charge
      distributions.
AB  - The importance of electrostatic interactions in soft matter and biological
      systems can often be traced to non-uniform charge effects, which are commonly
      described using a multipole expansion of the corresponding charge distribution.
      The standard approach when extracting the charge distribution of a given system
      is to treat the constituent charges as points. This can, however, lead to an
      overestimation of multipole moments of high order, such as dipole, quadrupole,
      and higher moments. Focusing on distributions of charges located on a spherical
      surface - characteristic of numerous biological macromolecules, such as globular
      proteins and viral capsids, as well as of inverse patchy colloids - we develop a
      novel way of representing spherical surface charge distributions based on the von
      Mises-Fisher distribution. This approach takes into account the finite spatial
      extension of individual charges, and leads to a simple yet powerful way of
      describing surface charge distributions and their multipole expansions. In this
      manner, we analyze charge distributions and the derived multipole moments of a
      number of different spherical configurations of identical charges with various
      degrees of symmetry. We show how the number of charges, their size, and the
      geometry of their configuration influence the behavior and relative importance of
      multipole magnitudes of different order. Importantly, we clearly demonstrate how
      neglecting the effect of charge size leads to an overestimation of high-order
      multipoles. The results of our work can be applied to construct analytical models
      of electrostatic interactions and multipole expansion of charged particles in
      diverse soft matter and biological systems.

PMID- 29345715
TI  - Tendon - function-related structure, simple healing process and mysterious
      ageing.
AB  - Tendons are connective tissue structures of paramount importance to human ability
      of locomotion. The understanding of their physiology and pathology is gaining
      importance as advances in regenerative medicine are being made today. So far,
      very few studies were conducted to extend the knowledge about pathology, healing
      response and management of tendon lesions. In this paper we summarise actual
      knowledge on structure, process of healing and ageing of the tendons. The
      structure of tendon is optimised for the best performance of the tissue. Despite
      the simplicity of the healing response, numerous studies showed that the problems
      with full recovery are common and much more significant than we thought; that is
      why we discussed the issue of immobilisation and mechanical stimulation during
      healing process. The phenomenon of tendons' ageing is poorly understood. Although
      it seems to be a natural and painless process, it is completely different from
      degeneration in tendinopathy. Recent studies of biological treatment reported
      faster and optimal healing of the tendons when augmented by growth factors and
      stem cells. Despite advances in biology of tendons, management of their injuries
      is still a challenge for physicians; therefore, further studies are required to
      improve treatment outcomes.

PMID- 29345716
TI  - Endodontium - together or separately?
AB  - Endodontium, otherwise referred to as pulp-dentin complex or endodont. This term
      includes two tooth tissues: dentin and pulp, which constitute a structural and
      functional unity. These tissues have a huge, inseparable influence on each other 
      the pulp (inter alia) nourishes the dentine, while the dentin forms a protective
      barrier for the pulp. They develop from the papillary tissue (Latin:
      papilladentis) from mesenchymal tissue. Nevertheless, in clinical practice this
      structural-functional complex is often treated as two separate tissues, and not
      as a whole. Adequate knowledge of the structure, function and protective
      mechanisms of the endodontium produces successful results in the treatment. The
      appropriate choice and application of the therapeutic methods and materials to
      the dentin secures vitality of both tissues of this complex.

PMID- 29345717
TI  - Vasoconstrictive responses of the cephalic vein during first-time cardiac
      implantable electronic device placement.
AB  - BACKGROUND: During cardiac implantable electronic device (CIED) implantation
      procedures cardiac leads have been mostly introduced transvenously. The
      associated injury to the selected vessel and adjacent tissues may induce reflex
      vasoconstriction. The aim of the study was to assess the incidence of cephalic
      vein (CV) vasoconstriction during first-time CIED implantation. MATERIALS AND
      METHODS: Of the 146 evaluated first-time CIED implantation procedures conducted
      in our centre in 2016, we selected those during which CV vasoconstriction was
      recorded. We focused on the stage of the procedure involving CV cutdown and/or
      axillary vein (AV)/subclavian vein (SV) puncture for lead insertion. Only cases
      documented via venography were considered. RESULTS: Vasoconstriction was observed
      in 11 patients (5 females and 6 males, mean age 59.0 +/- 21.2 years). The
      presence of this phenomenon affected the stage of CIED implantation involving
      cardiac lead insertion to the venous system, in severe cases, requiring a change
      of approach from CV cutdown to AV/SV puncture. The extent of vasoconstriction
      front propagation was limited to the nearest valves. Histological examinations of
      collected CV samples revealed an altered spatial arrangement of myocytes in the
      tunica media at the level of leaflet attachment. CONCLUSIONS: Cephalic vein
      vasoconstriction is a rare phenomenon associated with accessing the venous system
      during first-time CIED implantation. The propagation of CV constriction was
      limited by the location of the nearest valves.

PMID- 29345718
TI  - Evaluation of the morphological characteristic and sex differences of sternum by
      multi-detector computed tomography.
AB  - BACKGROUND: Sternum is one of the skeleton parts which have frequently congenital
      anomalies and variations are commonly used by researchers in determining sex. We
      evaluated the morphological characteristics and sex-related changes of the
      sternum in adult individuals using multidetector computed tomography in our
      study. MATERIALS AND METHODS: Two hundred adults (103 female and 97 male) aged
      between 18 and 87 years were evaluated. Utilising the morphological
      characteristics of the sternum based on the multislice images; length, width and
      the thickness of manubrium, length, width and the thickness of corpus sterni,
      total length of sternum, sternal angle, sternal index (SI), length of the xiphoid
      process, the thickness of xiphoid process, the number of indents of xiphoid
      process were measured and a total of 20 parameters were evaluated by adding age,
      height and weight to these variables. RESULTS: The mean length of the manubrium,
      the length of corpus sterni, the length of total sternum, SI, sternal angle were
      found in females 46.7 +/- 5.1, 86.6 +/- 9.7, 133.1 +/- 1.1, 54.47 +/- 10.0 and
      163.75 +/- 5.79; in males 51.2 +/- 6,102.4 +/- 13.3, 154.1 +/- 13.1, 50.11 +/-
      10.02 and 162.21 +/- 6.17, respectively. We found that Hyrtl's Law and SI did not
      provide adequate accuracy for sex determination in our patients. It has been
      detected that the length of the manubrium alone is not helpful for individual
      samples. Total length of the sternum was found to be more reliable than the
      length of the manubrium and the length of corpus sterni. We determined sternal
      cleft and sternal foramen as 0.5% and 3.5%, respectively. CONCLUSIONS: We suggest
      that the morphometric standards cannot be universally applied and can demonstrate
      individual differences. The standard rules must be implemented for every
      population.

PMID- 29345719
TI  - An anatomical variant: evaluation of accessory canals of the canalis sinuosus
      using cone beam computed tomography.
AB  - BACKGROUND: The anatomical variation of the anterior superior alveolar nerve
      described as canalis sinuosus (CS) is a less known structure of anterior maxilla.
      Due to the fact that it contains anterior superior alveolar nerve as well as
      veins and arteries, exact localisation of this structure will allow surgeons to
      avoid complications. Hence, the aim of this study was to verify the presence,
      reveal the frequency and characteristics of accessory canals of CS. MATERIALS AND
      METHODS: This study was based on retrospective evaluation of cone beam computed
      tomography (CBCT) scans. A total of 1460 CBCT images were analysed and collected
      data were noted. The following parameters were recorded: age, sex, presence or
      absence of CS, location in relation to the adjacent teeth and impaction of canine
      teeth. RESULTS: A total of 6668 accessory canals were found in 1460 CBCT images.
      Of these, 672 (46.0%) were from female patients, and 788 (54.0%) were from male
      patients. 1034 (70.8%) of 1460 images had at least one accessory canal of CS.
      Maxillary intercentral region is the area where accessory canals were seen most
      frequently (n = 653, 44.72%). CONCLUSIONS: Canalis sinuosus is a bony canal which
      is incidentally found and less known structure of anterior portion of maxilla.
      Knowing the accessory canals deriving from this structure will allow surgeons to
      avoid complications and non-integration after dental implant procedures.
      Conventional imaging modalities have limited value in detecting this
      neurovascular structures. Therefore CBCT may have an important role for accurate
      diagnosis to reveal anatomical variations.

PMID- 29345720
TI  - Effects of nicotine administration in rats on MMP2 and VEGF levels in periodontal
      membrane.
AB  - BACKGROUND: Nicotine is associated with increased incidence of periodontal
      disease and poor response to therapy. This article aimed at identifying the
      expression of matrix metalloproteinases 2 (MMPs2) and vascular endothelial growth
      factor (VEGF) proteins on extracellular matrix, fibrous distribution and
      angiogenetic development in periodontitis caused by nicotine effects on
      periodontal membrane. MATERIALS AND METHODS: In this experimental study, rats
      were divided into nicotine and control groups. While the rats in the nicotine
      group (n = 6) were administered 2 mg/kg nicotine sulphate for 28 days, the
      animals in the control group (n = 6) were only administered 1.5 mL physiologic
      saline solution subcutaneously for 28 days. RESULTS: Histological sections were
      prepared and immunohistochemically stained for MMP2 and VEGF. The sections
      stained with Trichrome-Masson were observed under light microscope. VEGF and MMP2
      immunoreactivity of periodontal gingiva and dentin was assessed by
      immunohistochemical staining. CONCLUSIONS: Nicotine reduces MMP production,
      disrupts collagen synthesis and causes periodontitis. We observed that nicotine
      increases periodontitis by disrupting periodontal membrane and prevents tooth to
      anchor in dental alveoli by disrupting epithelial structure.

PMID- 29345721
TI  - Sectioned images and surface models of a cadaver head with reference to botulinum
      neurotoxin injection.
AB  - BACKGROUND: The aim of this study is to elucidate the anatomical considerations
      with reference to botulinum neurotoxin type A (BTX) injection, on sectioned
      images and surface models, using Visible Korean. These can be used for medical
      education and clinical training in the field of facial surgery. MATERIALS AND
      METHODS: Serially sectioned images of the head were obtained from a cadaver.
      Significant anatomic structures in the sectioned images were outlined and
      assembled to create a surface model. RESULTS: The PDF file (27.8 MB) of the
      stacked models can be accessed for free. The file can also be obtained from the
      authors by email. Using this file, important anatomical structures associated
      with the BTX injection can be investigated in the sectioned images. All surface
      models and stereoscopic structures related with the BTX injection are described
      in real time. CONCLUSIONS: We hope that these state-of-the-art sectioned images,
      outlined images, and surface models will assist students and trainees in
      acquiring a better understanding of the anatomy associated with the BTX
      injection.

PMID- 29345722
TI  - Morphometric properties of the tensor fascia lata muscle in human foetuses.
AB  - BACKGROUND: In neonatal and early childhood surgeries such as meningomyelocele
      repairs, closing deep wounds and oncological treatment, tensor fasciae lata (TFL)
      flaps are used. However, there are not enough data about structural properties of
      TFL in foetuses, which can be considered as the closest to neonates in terms of
      sampling. This study's main objective is to gather data about morphological
      structures of TFL in human foetuses to be used in newborn surgery. MATERIALS AND
      METHODS: Fifty formalin-fixed foetuses (24 male, 26 female) with gestational age
      ranging from 18 to 30 weeks (mean 22.94 +/- 3.23 weeks) were included in the
      study. TFL samples were obtained by bilateral dissection and then surface area,
      width and length parameters were recorded. Digital callipers were used for length
      and width measurements whereas surface area was calculated using digital image
      analysis software. RESULTS: No statistically significant differences were found
      in terms of numerical value of parameters between sides and sexes (p > 0.05).
      Linear functions for TFL surface area, width, anterior and posterior margin
      lengths were calculated as y = -225.652 + 14.417 * age (weeks), y = -5.571 +
      0.595 * age (weeks), y = -4.276 + 0.909 * age (weeks), and y = -4.468 + 0.779 *
      age (weeks), respectively. CONCLUSIONS: Linear functions for TFL surface area,
      width and lengths can be used in designing TFL flap dimensions in newborn
      surgery. In addition, using those described linear functions can also be
      beneficial in prediction of TFL flap dimensions in autopsy studies.

PMID- 29345723
TI  - Anatomical characteristics of the lingual foramen in ancient skulls: a cone beam
      computed tomography study in an Anatolian population.
AB  - BACKGROUND: The purpose of this study is to evaluate the anatomical features of
      lingual foramina and their bony canals in Anatolian ancient mandibles (9-10th
      century) by using cone beam computed tomography (CBCT). MATERIALS AND METHODS:
      Fifty-eight ancient dry mandibles were scanned with CBCT. Lingual foramina were
      grouped into midline, paramedian, posterior foramina and combination of these
      groups. Midline group was also classified according to internal surface of the
      mandible (gonial tubercles [GTs]). The incidence, vertical distance and diameter
      of lingual foramina were measured according to age groups and gender. RESULTS:
      The incidence of the lingual foramen was 96.6%. Midline of the symphysis had the
      highest incidence (34.4%) of foramina (p < 0.05), followed by both midline and
      paramedian type (32.8%; p < 0.05). Classification in terms of GT represented
      class 3 as the most encountered group (28.6%). Number of foramina observed in the
      mandibles ranged from 0 to 6 with the incidence of 3.4% and 32.8%, respectively.
      The male and < 35 years groups presented larger measurement values in midline
      region (p < 0.05). CONCLUSIONS: Mandibular lingual foramina and bony canals are
      frequently present in ancient mandibles. When compared with modern subjects,
      similar findings are observed according to published literatures. CBCT is also
      proved to be an effective imaging modality in the detection of lingual foramina
      and canals in anthropological studies.

PMID- 29345724
TI  - Effects of Cognitive Training on Cognition and Quality of Life of Older Persons
      with Dementia.
AB  - OBJECTIVES: To evaluate the effect of cognitive training on cognition and health
      related quality of life (HRQoL) in community-dwelling persons with dementia.
      DESIGN: Single-blind randomized controlled trial with 3- and 9-month follow-up.
      SETTING: Adult day care centers in Helsinki, Finland. PARTICIPANTS: Older
      individuals with mild to moderate dementia living at home and attending adult day
      care twice a week (N = 147; mean age 83, 72% female, 63% at mild stage of
      dementia). INTERVENTION: A systematic 12-week training program focused on
      subskills of executive function: attention, working memory, cognitive
      flexibility, and planning. The intervention group (n = 76) underwent cognitive
      training twice a week for 45 minutes, and the control group (n = 71) attended day
      care as usual. MEASUREMENTS: Primary outcomes were the Alzheimer's Disease
      Assessment Scale-Cognitive subscale (ADAS-Cog) for global cognition and the 15
      dimensional instrument (15D) for HRQoL. The outcomes were measured at baseline
      and 3 and 9 months. RESULTS: Both groups deteriorated in global cognition and
      HRQoL during follow-up, and there were no differences between the two groups in
      change on the ADAS-Cog (P = .43) or 15D (P = .61) over time (adjusted for age and
      sex). At 3 months, changes were 0.8 (95% confidence interval (CI) = -0.2-1.8) for
      the intervention group and 1.7 (95% CI = 0.6-2.7) for the control group on the
      ADAS-Cog and -0.040 (95% CI = -0.058 to -0.021) for the intervention group and 
      0.037 (95% CI = -0.056 to -0.018) for the control group on the 15D. CONCLUSION:
      Systematic cognitive training had no effect on global cognition or HRQoL in
      community-living persons with mild to moderate dementia.

PMID- 29345726
TI  - ?

PMID- 29345725
TI  - Polyols and UV-sunscreens in the Prasiola-clade (Trebouxiophyceae, Chlorophyta)
      as metabolites for stress response and chemotaxonomy.
AB  - In many regions of the world, aeroterrestrial green algae of the Trebouxiophyceae
      (Chlorophyta) represent very abundant soil microorganisms, and hence their
      taxonomy is crucial to investigate their physiological performance and ecological
      importance. Due to a lack in morphological features, taxonomic and phylogenetic
      studies of Trebouxiophycean algae can be a challenging task. Since chemotaxonomic
      markers could be a great assistance in this regard, 22 strains of aeroterrestrial
      Trebouxiophyceae were chemically screened for their polyol-patterns as well as
      for mycosporine-like amino acids (MAAs) in their aqueous extracts using RP-HPLC
      and LC-MS. d-sorbitol was exclusively detected in members of the Prasiolaceae
      family. The novel MAA prasiolin and a related compound ("prasiolin-like") were
      present in all investigated members of the Prasiola-clade, but missing in all
      other tested Trebouxiophyceae. While prasiolin could only be detected in field
      material directly after extraction, the "prasiolin-like" compound present in the
      other algae was fully converted into prasiolin after 24 h. These findings suggest
      d-sorbitol and prasiolin-like compounds are suitable chemotaxonomic markers for
      the Prasiolaceae and Prasiola-clade, respectively. Additional UV-exposure
      experiments with selected strains show that MAA formation and accumulation can be
      induced, supporting their role as UV-sunscreen.

PMID- 29345727
TI  - The Petal Project: An innovation in sexual healthcare and education for Kenyan
      schoolgirl.
AB  - In the western province of Nyanza in Kenya, girls and women face an issue all too
      common in the developing world-little or no access to affordable means to
      effectively managing their menstrual flow. As a result, many stay at home or drop
      out of school because they are teased and embarrassed. Some approach men for
      money to buy pads and are forced, in return, to engage in transactional sex. The
      girls may not be able to return to school at all due to pregnancy. The story
      literally and figuratively continues to cycle, keeping girls in positions of
      dependency and poverty. In May 2011, two visiting nursing faculty conducting
      health clinics with students, were approached by a young male school volunteer
      who shared his observations and unease with what he saw happening. Concerns
      shared that day spawned an initiative known as the Petal Project, which has
      yielded thousands of starter kits hand-sewn and delivered to girls in Kenya. The
      Petal Project has grown in popularity and participation on their college campus
      and in neighboring communities. Since its inception, this initiative has expanded
      to include over six countries and has positively impacted the lives of hundreds
      of givers and receivers.

PMID- 29345728
TI  - Analytical performance of the ThyroSeq v3 genomic classifier for cancer diagnosis
      in thyroid nodules.
AB  - BACKGROUND: Molecular tests have clinical utility for thyroid nodules with
      indeterminate fine-needle aspiration (FNA) cytology, although their performance
      requires further improvement. This study evaluated the analytical performance of
      the newly created ThyroSeq v3 test. METHODS: ThyroSeq v3 is a DNA- and RNA-based
      next-generation sequencing assay that analyzes 112 genes for a variety of genetic
      alterations, including point mutations, insertions/deletions, gene fusions, copy
      number alterations, and abnormal gene expression, and it uses a genomic
      classifier (GC) to separate malignant lesions from benign lesions. It was
      validated in 238 tissue samples and 175 FNA samples with known surgical follow
      up. Analytical performance studies were conducted. RESULTS: In the training
      tissue set of samples, ThyroSeq GC detected more than 100 genetic alterations,
      including BRAF, RAS, TERT, and DICER1 mutations, NTRK1/3, BRAF, and RET fusions,
      22q loss, and gene expression alterations. GC cutoffs were established to
      distinguish cancer from benign nodules with 93.9% sensitivity, 89.4% specificity,
      and 92.1% accuracy. This correctly classified most papillary, follicular, and
      Hurthle cell lesions, medullary thyroid carcinomas, and parathyroid lesions. In
      the FNA validation set, the GC sensitivity was 98.0%, the specificity was 81.8%,
      and the accuracy was 90.9%. Analytical accuracy studies demonstrated a minimal
      required nucleic acid input of 2.5 ng, a 12% minimal acceptable tumor content,
      and reproducible test results under variable stress conditions. CONCLUSIONS: The
      ThyroSeq v3 GC analyzes 5 different classes of molecular alterations and provides
      high accuracy for detecting all common types of thyroid cancer and parathyroid
      lesions. The analytical sensitivity, specificity, and robustness of the test have
      been successfully validated and indicate its suitability for clinical use. Cancer
      2018;124:1682-90. (c) 2018 American Cancer Society.

PMID- 29345729
TI  - Sinus node dysfunction after heart transplantation-An analysis of risk factors
      and atrial pacing burden.
AB  - INTRODUCTION: We investigated the development of sinus node dysfunction (SND)
      requiring pacemaker implantation after heart transplant (HTx) especially
      regarding pacing burden in these patients. PATIENTS AND METHODS: Patients
      requiring a pacemaker for SND were compared to all other patients in an HTx
      cohort including transplant patients from 1981 to 2016. RESULTS: Sinus node
      dysfunction requiring pacemaker implantation developed in 118 patients (10%).
      These patients had received a biatrial anastomosis more frequently than those in
      the No SND group 95.8% vs 90.0% (P = .042). The ratio of reperfusion time to
      aortic cross-clamp time was significantly smaller in the SND group compared to
      the No SND group 71.7% vs 80.3% (P = .033). This also holds for the ratio of
      reperfusion time to ischemia time, which was 23.2% and 28.6%, respectively (P =
      .032). Pacing burden decreased from 90.5% to 66.3% after 2 years and remained
      around this value in the remaining 4 years of follow-up. CONCLUSION: We
      identified the biatrial anastomosis and a low ratio of reperfusion time to aortic
      cross-clamp time as well as to ischemia time as risk factors for SND requiring
      pacing. After implantation pacemakers continue to pace for over 60% of the time
      after 6 years.

PMID- 29345730
TI  - Regional pattern of microgliosis in sporadic Creutzfeldt-Jakob disease in
      relation to phenotypic variants and disease progression.
AB  - AIMS: The aim of this study was to describe the regional profiles of microglial
      activation in sporadic Creutzfeldt-Jakob disease (sCJD) subtypes and analyse the
      influence of prion strain, disease duration and codon 129 genotype. METHODS: We
      studied the amount/severity and distribution of activated microglia, protease
      resistant prion protein (PrPSc ) spongiform change, and astrogliosis in eight
      regions of 57 brains, representative of the entire spectrum of sCJD subtypes.
      RESULTS: In each individual subtype, the regional extent and distribution of
      microgliosis significantly correlated with PrPSc deposition and spongiform
      change, leading to subtype-specific 'lesion profiles'. However, large differences
      in the ratio between PrPSc load or the score of spongiform change and microglial
      activation were seen among disease subtypes. Most significantly, atypical sCJD
      subtypes such as VV1 and MM2T showed a degree of microglial activation comparable
      to other disease variants despite the relatively low PrPSc deposition and the
      less severe spongiform change. Moreover, the mean microglial total load was
      significantly higher in subtype MM1 than in MM2C, whereas the opposite was true
      for the PrPSc and spongiform change total loads. Finally, some sCJD subtypes
      showed distinctive regional cerebellar profiles of microgliosis characterized by
      a high granular/molecular layer ratio (MV2K) and/or a predominant involvement of
      white matter (MVK and MM2T). CONCLUSIONS: Microglial activation is an early event
      in sCJD pathogenesis and is strongly influenced by prion strain, PRNP codon 129
      genotype and disease duration. Microglial lesion profiling, by highlighting
      strain-specific properties of prions, contributes to prion strain
      characterization and classification of human prion diseases, and represents a
      valid support to molecular and histopathologic typing.

PMID- 29345731
TI  - Student evaluations of teaching (SET): Guidelines for their use.
AB  - Student evaluations of teaching (SET) provide a structured way of collecting
      feedback from students about the course and teacher's effectiveness. We reviewed
      literature describing use of SET across a broad range of disciplines in
      undergraduate and graduate education to provide guidelines for faculty in using
      SET in a nursing or other health professions program. On SET tools, students
      typically rate their satisfaction with a course and perceptions about the quality
      of the teaching. It is important to evaluate SET tools prior to their use
      including pilot testing tools with students because studies show students may not
      interpret items or questions on a SET tool as faculty intended. Common uses of
      the evaluation data from SET include improvement of courses and teaching, and for
      personnel decisions.

PMID- 29345732
TI  - Near Visual Impairment Incidence in Relation to Diabetes in Older People: The
      Three-Cities Study.
AB  - OBJECTIVES: To characterize the relationship between diabetes mellitus (DM) and
      future risk of near vision impairment (VI) in a community-dwelling population of
      older people. DESIGN: Seven-year population-based longitudinal study. SETTING:
      Three-Cities Study, a French prospective study designed to assess the risk of
      cognitive and functional decline attributable to vascular factors. PARTICIPANTS:
      Community-dwelling individuals aged 65 and older (N = 8,412). MEASUREMENTS: DM
      was determined at baseline according to self-reported DM, antidiabetic treatment,
      and fasting blood glucose. Near visual acuity was measured at baseline and 2, 4,
      and 7 years later. Near VI was defined as a Snellen score greater than 20/30.
      RESULTS: DM was associated with a higher risk of near VI in an adjusted model
      (hazard ratio (HR) = 1.24, 95% confidence interval (CI) = 1.02-1.52, P = .03).
      Because of an interaction between Body Mass Index (BMI) and diagnosed DM, the
      longitudinal analyses were stratified according to BMI category. DM was
      associated with greater risk of near VI only in underweight (BMI <21.0 kg/m2 , HR
      = 2.89, 95% CI = 1.18-7.03) and normal-weight (BMI 21.0-24.9 kg/m2 , HR = 1.60,
      95% CI = 1.10-2.32), but not overweight (P = .69) and obese (P = .09) subjects.
      CONCLUSION: DM is a risk factor for near VI in older people, particularly in
      those with a low or normal BMI. This risk profile should be taken into account in
      older adults to support their independence.

PMID- 29345733
TI  - Putative mechanisms of cognitive decline with implications for clinical research
      and practice.
AB  - Multiple intrinsic and extrinsic mechanisms contribute to vulnerability of
      cognitive decline and nurses play a significant role in assisting individuals and
      families to use strategies for healthy cognitive aging. The objective of this
      narrative review is to provide a synthesis of the intrinsic and extrinsic
      mechanisms of cognitive decline and conditions that are associated with cognitive
      decline. Well-established intrinsic mechanisms of cognitive decline include
      aging, apolipoprotein E (APOE) epsilon4 carrier status, SORL1 mutations,
      neuroinflammation, mitochondrial dysfunction, amyloid deposition, and
      demyelination. Extrinsic risk factors include obesity, diabetes, hypertension,
      elevated lipid panel, metabolic syndrome, depression, traumatic brain injury,
      substance use, heart failure, and stroke. The various definitions of cognitive
      decline as well as the intrinsic and extrinsic factors that impact cognition as
      humans age should be incorporated in future clinical research studies. Nurses may
      use this information to help patients make lifestyle choices regarding cognitive
      health.

PMID- 29345734
TI  - Glove port path for transanal resection of rectal lesion - a video vignette.

PMID- 29345735
TI  - Landscape simplification reduces classical biological control and crop yield.
AB  - Agricultural intensification resulting in the simplification of agricultural
      landscapes is known to negatively impact the delivery of key ecosystem services
      such as the biological control of crop pests. Both conservation and classical
      biological control may be influenced by the landscape context in which they are
      deployed; yet studies examining the role of landscape structure in the
      establishment and success of introduced natural enemies and their interactions
      with native communities are lacking. In this study, we investigated the
      relationship between landscape simplification, classical and conservation
      biological control services and importantly, the outcome of these interactions
      for crop yield. We showed that agricultural simplification at the landscape scale
      is associated with an overall reduction in parasitism rates of crop pests.
      Additionally, only introduced parasitoids were identified, and no native
      parasitoids were found in crop habitat, irrespective of agricultural landscape
      simplification. Pest densities in the crop were lower in landscapes with greater
      proportions of semi-natural habitats. Furthermore, farms with less semi-natural
      cover in the landscape and consequently, higher pest numbers, had lower yields
      than farms in less agriculturally dominated landscapes. Our study demonstrates
      the importance of landscape scale agricultural simplification in mediating the
      success of biological control programs and highlights the potential risks to
      native natural enemies in classical biological control programs against native
      insects. Our results represent an important contribution to an understanding of
      the landscape-mediated impacts on crop yield that will be essential to
      implementing effective policies that simultaneously conserve biodiversity and
      ecosystem services.

PMID- 29345736
TI  - Palbociclib in combination with letrozole as first-line treatment for advanced
      breast cancer: A Japanese phase II study.
AB  - This single-arm, open-label, phase II study in 42 Japanese postmenopausal
      patients with estrogen receptor-positive/human epidermal growth factor receptor 2
      negative (ER+/HER2-) advanced breast cancer evaluated the efficacy, safety, and
      pharmacokinetics of first-line palbociclib (125 mg once daily, 3 weeks on/1 week
      off) coadministered with letrozole (2.5 mg once daily). Primary endpoint of
      investigator-assessed 1-year progression-free survival (PFS) probability was
      75.0% (90% CI, 61.3%-84.4%), far surpassing the 40% lower limit of the 90% CI
      supporting efficacy. Median duration of treatment was 438 days. Among secondary
      efficacy measures, median PFS was not reached (95% CI, 16.7: not estimable),
      17/42 patients (40.5%) had an objective response, 36/42 (85.7%) maintained
      disease control, and 27/42 (64.3%) remained in follow-up. Median overall survival
      was not reached, and 1-year survival probability was 92.9% (95% CI, 79.5%-97.6%).
      Results of intensive pharmacokinetics in a subset of 6 patients showed
      palbociclib steady-state mean area under the plasma concentration-time curve over
      the dosing interval [tau] and mean maximum plasma concentration were 1979 ng.h/mL
      and 124.7 ng/mL, respectively. For day 15 plasma samples from cycles 1 and 2,
      geometric mean of the within-patient mean trough concentration was 90.1 ng/mL.
      The most common treatment-related adverse events were neutropenia (100%) and
      stomatitis (73.8%). There was 1 case of treatment-related febrile neutropenia.
      Toxicities were generally tolerated and manageable by dose modifications and/or
      medical care. Efficacy and safety of first-line palbociclib plus letrozole
      therapy is supported in Japanese postmenopausal patients with treatment-naive
      ER+/HER2- advanced breast cancer.

PMID- 29345738
TI  - Elucidation of the Oxygen Reduction Volcano in Alkaline Media using a Copper
      Platinum(111) Alloy.
AB  - The relationship between the binding of the reaction intermediates and oxygen
      reduction activity in alkaline media was experimentally explored. By introducing
      Cu into the 2nd surface layer of a Pt(111) single crystal, the surface reactivity
      was tuned. In both 0.1 m NaOH and 0.1 m KOH, the optimal catalyst should exhibit
      OH binding circa 0.1 eV weaker than Pt(111), via a Sabatier volcano; this
      observation suggests that the reaction is mediated via the same surface bound
      intermediates as in acid, in contrast to previous reports. In 0.1 m KOH, the
      alloy catalyst at the peak of the volcano exhibits a maximum activity of 101+/-8
      mA cm-2 at 0.9 V vs. a reversible hydrogen electrode (RHE). This activity
      constitutes a circa 60-fold increase over Pt(111) in 0.1 m HClO4 .

PMID- 29345739
TI  - Exact Mapping from Many-Spin Hamiltonians to Giant-Spin Hamiltonians.
AB  - Thermodynamic and spectroscopic data of exchange-coupled molecular spin clusters
      (e.g. single-molecule magnets) are routinely interpreted in terms of two
      different models: the many-spin Hamiltonian (MSH) explicitly considers couplings
      between individual spin centers, while the giant-spin Hamiltonian (GSH) treats
      the system as a single collective spin. When isotropic exchange coupling is weak,
      the physical compatibility between both spin Hamiltonian models becomes a serious
      concern, due to mixing of spin multiplets by local zero-field splitting (ZFS)
      interactions ('S-mixing'). Until now, this effect, which makes the mapping MSH
      >GSH ('spin projection') non-trivial, had only been treated perturbationally (up
      to third order), with obvious limitations. Here, based on exact diagonalization
      of the MSH, canonical effective Hamiltonian theory is applied to construct a GSH
      that exactly matches the energies of the relevant (2S+1) states comprising an
      effective spin multiplet. For comparison, a recently developed strategy for the
      unique derivation of effective ('pseudospin') Hamiltonians, now routinely
      employed in ab initio calculations of mononuclear systems, is adapted to the
      problem of spin projection. Expansion of the zero-field Hamiltonian and the
      magnetic moment in terms of irreducible tensor operators (or Stevens operators)
      yields terms of all ranks k (up to k=2S) in the effective spin. Calculations
      employing published MSH parameters illustrate exact spin projection for the well
      investigated [Ni(hmp)(dmb)Cl]4 ('Ni4 ') single-molecule magnet, which displays
      weak isotropic exchange (dmb=3,3-dimethyl-1-butanol, hmp- is the anion of 2
      hydroxymethylpyridine). The performance of the resulting GSH in finite field is
      assessed in terms of EPR resonances and diabolical points. The large tunnel
      splitting in the M=+/- 4 ground doublet of the S=4 multiplet, responsible for
      fast tunneling in Ni4 , is attributed to a Stevens operator with eightfold
      rotational symmetry, marking the first quantification of a k=8 term in a spin
      cluster. The unique and exact mapping MSH->GSH should be of general importance
      for weakly-coupled systems; it represents a mandatory ultimate step for comparing
      theoretical predictions (e.g. from quantum-chemical calculations) to ZFS,
      hyperfine or g-tensors from spectral fittings.

PMID- 29345737
TI  - Present status and future perspective of peptide-based vaccine therapy for
      urological cancer.
AB  - Use of peptide-based vaccines as therapeutics aims to elicit immune responses
      through antigenic epitopes derived from tumor antigens. Peptide-based vaccines
      are easily synthesized and lack significant side-effects when given in vivo.
      Peptide-based vaccine therapy against several cancers including urological
      cancers has made progress for several decades, but there is no worldwide approved
      peptide vaccine. Peptide vaccines were also shown to induce a high frequency of
      immune response in patients accompanied by clinical efficacy. These data are
      discussed in light of the recent progression of immunotherapy caused by the
      addition of immune checkpoint inhibitors thus providing a general picture of the
      potential therapeutic efficacy of peptide-based vaccines and their combination
      with other biological agents. In this review, we discuss the mechanism of the
      antitumor effect of peptide-based vaccine therapy, development of our peptide
      vaccine, recent clinical trials using peptide vaccines for urological cancers,
      and perspectives of peptide-based vaccine therapy.

PMID- 29345740
TI  - Accurate Etiological Diagnosis of Dementia Contributes to Better Clinical Care.

PMID- 29345741
TI  - Geriatric Syndromes, Dementia Subtypes, Gizmo Idolatry.

PMID- 29345742
TI  - Cognitive Training for Older Adults: What Works?

PMID- 29345743
TI  - Refining mortality estimates in shark demographic analyses: a Bayesian inverse
      matrix approach.
AB  - Leslie matrix models are an important analysis tool in conservation biology that
      are applied to a diversity of taxa. The standard approach estimates the finite
      rate of population growth (lambda) from a set of vital rates. In some instances,
      an estimate of lambda is available, but the vital rates are poorly understood and
      can be solved for using an inverse matrix approach. However, these approaches are
      rarely attempted due to prerequisites of information on the structure of age or
      stage classes. This study addressed this issue by using a combination of Monte
      Carlo simulations and the sample-importance-resampling (SIR) algorithm to solve
      the inverse matrix problem without data on population structure. This approach
      was applied to the grey reef shark (Carcharhinus amblyrhynchos) from the Great
      Barrier Reef (GBR) in Australia to determine the demography of this population.
      Additionally, these outputs were applied to another heavily fished population
      from Papua New Guinea (PNG) that requires estimates of lambda for fisheries
      management. The SIR analysis determined that natural mortality (M) and total
      mortality (Z) based on indirect methods have previously been overestimated for C.
      amblyrhynchos, leading to an underestimated lambda. Updated distributions of Z
      and lambda were produced for the GBR population and corrected obvious error in
      the demographic parameters for the PNG population. This approach provides
      opportunity for the inverse matrix approach to be applied more broadly to
      situations where information on population structure is lacking.

PMID- 29345744
TI  - Land surveys show regional variability of historical fire regimes and dry forest
      structure of the western United States.
AB  - An understanding of how historical fire and structure in dry forests (ponderosa
      pine, dry mixed conifer) varied across the western United States remains
      incomplete. Yet, fire strongly affects ecosystem services, and forest restoration
      programs are underway. We used General Land Office survey reconstructions from
      the late 1800s across 11 landscapes covering ~1.9 million ha in four states to
      analyze spatial variation in fire regimes and forest structure. We first
      synthesized the state of validation of our methods using 20 modern validations,
      53 historical cross-validations, and corroborating evidence. These show our
      method creates accurate reconstructions with low errors. One independent modern
      test reported high error, but did not replicate our method and made many
      calculation errors. Using reconstructed parameters of historical fire regimes and
      forest structure from our validated methods, forests were found to be non-uniform
      across the 11 landscapes, but grouped together in three geographical areas. Each
      had a mixture of fire severities, but dominated by low-severity fire and low
      median tree density in Arizona, mixed-severity fire and intermediate to high
      median tree density in Oregon-California, and high-severity fire and intermediate
      median tree density in Colorado. Programs to restore fire and forest structure
      could benefit from regional frameworks, rather than one size fits all.

PMID- 29345745
TI  - Comparison of Flow Cytometric Methods for the Enumeration of Residual Leucocytes
      in Leucoreduced Blood Products: A Multicenter Study.
AB  - The BD FACSViaTM System features novel designs in hardware, software, and
      instrument QC. We compared the performance of the BD FACSVia System using the BD
      LeucocountTM kit with the BD FACSCaliburTM flow cytometer. Leucoreduced platelet
      (PLT, n = 252) and red blood cell (RBC, n = 278) specimens were enrolled at four
      sites. Each specimen was stained in four tubes using the BD Leucocount kit
      reagents and acquired on the two systems. BD Leucocount Control cells (high and
      low) were used to evaluate the inter-site reproducibility on the BD FACSVia
      System at three sites over 20 days. Deming regression and Bland-Altman analysis
      were performed to determine the WBC absolute counts on the BD FACSVia System vs.
      the BD FACSCalibur system. Assay accuracy for the range of 0-350 WBCs/ul was
      adequate. For samples with <25 WBCs/ul, the bias with 95% limits of agreement was
      0.136 (-1.897 to 2.169) WBC/ul for PLTs (n = 184) and 0.170 (-2.025 to 2.365)
      WBC/ul for RBCs (n = 193). For inter-site reproducibility, the CV% was 6.46%
      (upper 95% CI 7.16%) for the PLT high control and 9.49% (10.52%) for the PLT low
      control. The CV% was 7.51% (8.32%) for the RBC high control and 10.76% (11.92%)
      for the RBC low control. The BD FACSVia System reported equivalent results of WBC
      absolute counts for leucoreduced PLT and RBC samples compared to the BD
      FACSCalibur system. The inter-laboratory reproducibility of the BD FACSVia System
      met study specifications. (c) 2018 The Authors. Cytometry Part A Published by
      Wiley Periodicals, Inc. on behalf of ISAC.

PMID- 29345747
TI  - Recurrent IgA nephropathy after renal transplantation and steroid withdrawal.
AB  - Immunoglobulin A nephropathy (IgAN) is the most common primary
      glomerulonephritis; the reported recurrence rate of IgAN after renal
      transplantation is as high as 13%-50%. The impact of immunosuppressive therapy
      and steroid withdrawal on the risk of recurrence of IgAN is still under debate.
      We performed a retrospective single-center study, selecting 123 kidney
      transplants (rtx) in 120 patients, between January 1995 and December 2012, with
      IgAN on the native kidney. In 51 of 123 transplants, at least one post
      transplantation biopsy for clinical indication was performed; in 28 of 51
      transplants, IgAN recurrence (IgANr) was demonstrated. This group (G1; N = 28)
      was compared with a group without IgANr (G2; N = 23). In our study, clinically
      evident IgANr rate was 54.9% (28/51) on biopsied patients. At discharge, the use
      of the immunosuppressant drugs (tacrolimus, cyclosporine A, mycophenolate
      mofetil, azathioprine, mTor inhibitors) was not associated with an increased risk
      of IgANr (P = NS). At discharge, all patients were steroid treated. Neither the
      use of tacrolimus, mycophenolate mofetil, nor mTor inhibitors (mTori) at biopsy
      time were associated with IgANr. However, IgANr was significantly higher in
      patients who experienced steroid withdrawal at any post-transplantation time (OR
      7.7 P = .03). The median time to recurrence after steroid withdrawal was 59
      months (min 4.18, max 113.2).

PMID- 29345748
TI  - Kudingcha and Fuzhuan Brick Tea Prevent Obesity and Modulate Gut Microbiota in
      High-Fat Diet Fed Mice.
AB  - SCOPE: Kudingcha (KDC) from Ilex kudingcha and Fuzhuan brick tea (FBT) are
      popular beverages in China, and their preventive and therapeutic roles in
      metabolic disorders have been reported. However, the relationship between the gut
      microbiota modulatory effects of KDC and FBT and prevention of obesity is still
      not clearly understood. METHODS AND RESULTS: KDC and FBT are tested individually
      for their capacities to prevent obesity and modulate the gut microbiota in high
      fat diet (HFD) fed C57BL/6J mice. The results show that both KDC and FBT
      supplementation could modulate oxidative injury, inflammation, lipid metabolism,
      and reduce HFD induced obesity significantly. Both KDC and FBT could enhance the
      diversity of gut microbiota. KDC could reduce the relative abundance of
      Erysipelotrichaceae, while FBT could reduce the ratio of Firmicutes to
      Bacteroidetes and enhance the relative abundance of Bifidobacteriaceae.
      CONCLUSION: These findings suggest that KDC and FBT could attenuate features of
      the metabolic syndrome in HFD-fed mice, which might be due to the modulation of
      gut microbiota by KDC and FBT.

PMID- 29345746
TI  - History of genome editing in yeast.
AB  - For thousands of years humans have used the budding yeast Saccharomyces
      cerevisiae for the production of bread and alcohol; however, in the last 30-40
      years our understanding of the yeast biology has dramatically increased, enabling
      us to modify its genome. Although S. cerevisiae has been the main focus of many
      research groups, other non-conventional yeasts have also been studied and
      exploited for biotechnological purposes. Our experiments and knowledge have
      evolved from recombination to high-throughput PCR-based transformations to highly
      accurate CRISPR methods in order to alter yeast traits for either research or
      industrial purposes. Since the release of the genome sequence of S. cerevisiae in
      1996, the precise and targeted genome editing has increased significantly. In
      this 'Budding topic' we discuss the significant developments of genome editing in
      yeast, mainly focusing on Cre-loxP mediated recombination, delitto perfetto and
      CRISPR/Cas.

PMID- 29345749
TI  - Self-production of oxygen system CaO2 /MnO2 @PDA-MB for the photodynamic therapy
      research and switch-control tumor cell imaging.
AB  - Photodynamic therapy (PDT) holds promise in biochemical study and tumor
      treatment. A novel multifunctional nanosystem CaO2 /MnO2 @polydopamine (PDA)
      methylene blue (MB) nanosheet (CMP-MB) was designed. CaO2 nanoparticles were
      encapsulated by MnO2 nanosheet, and then PDA was coated on the surface of CaO2
      /MnO2 nanosheets, which could adsorb photosensitizer MB through hydrophobic
      interaction or pi-pi stacking. In this nanosystem, CaO2 /MnO2 had the ability of
      self-production of oxygen, which solved the problem of tumor hypoxia largely.
      Moreover, it is worth mentioning that the fluorescence of MB was suppressed by
      MnO2 , while its emission was triggered in the simulated tumor microenvironment.
      Therefore, CMP-MB nanosheet could be used to switch-control cell imaging
      potentially. 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide
      testing and Live/Dead assay confirmed CMP-MB nanosheet had fewer side effects
      without illumination while it destroyed Hela cell with the illumination of light.
      Vitro cell experiment demonstrated CMP-MB nanosheet could achieve tumor
      microenvironment responsive imaging and inhibit tumor cell growth under
      illumination effectively. Therefore, the system has great potential for PDT
      application and switch-control tumor cell imaging. (c) 2018 Wiley Periodicals,
      Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2544-2552, 2018.

PMID- 29345750
TI  - Mobility Trajectories at the End of Life: Comparing Clinical Condition and Latent
      Class Approaches.
AB  - OBJECTIVES: To assess mobility disability trajectories before death in a large
      sample of very old adults using two analytical approaches to determine how well
      they corresponded. DESIGN: Decedent sample from the Health, Aging and Body
      Composition (Health ABC) Study. Data were collected between 1997 and 2015.
      SETTING: Pittsburgh, Pennsylvania, and Memphis, Tennessee. PARTICIPANTS:
      Individuals randomly selected from well-functioning white Medicare beneficiaries
      and all black community residents meeting age criteria (70-79) (N = 3,075).
      MEASUREMENTS: Participants were interviewed in person or by phone at least every
      six months throughout the study. Of the 1,991 participants who died by the end of
      the study, 1,410 had been interviewed for 3 years before death, including an
      interview 6 months before dying. We analyzed self-reported mobility collected
      prospectively at 6-month intervals during the last 3 years of life. We derived
      trajectories in two ways: by averaging decline within decedent groups
      prespecified according to clinical conditions and by estimating trajectory models
      using maximum-likelihood semiparametric modeling. RESULTS: Ninety-eight percent
      of decedents were classified according to 4 prespecified clinical conditions
      (sudden death, terminal, organ failure, frailty), which produced groups with
      different characteristics. Five disability trajectories were identified: late
      decline, progressive disability, moderate disability, early decline, and
      persistent disability. Disability trajectory and clinical condition grouping
      confirmed previous research but were only marginally related. CONCLUSION: Derived
      disability trajectories and grouping according to clinical condition provide
      useful information about different facets of the end-of-life experience. The lack
      of fit between them suggests a need for greater attention to heterogeneity in
      disability in the period before death.

PMID- 29345751
TI  - First evidence of freezing tolerance in a resurrection plant: insights into
      molecular mobility and zeaxanthin synthesis in the dark.

PMID- 29345752
TI  - Oxidative Mechanochemistry: Direct, Room-Temperature, Solvent-Free Conversion of
      Palladium and Gold Metals into Soluble Salts and Coordination Complexes.
AB  - Noble metals are valued, critical elements whose chemical activation or recycling
      is challenging, and traditionally requires high temperatures, strong acids or
      bases, or aggressive complexation agents. By using elementary palladium and gold,
      demonstrated here is the use of mechanochemistry for noble-metal activation and
      recycling by mild, clean, solvent-free, and room-temperature chemistry. The
      process leads to direct, efficient, one-pot conversion of the metals, including
      spent catalysts, into either simple water-soluble salts or metal-organic
      catalysts.

PMID- 29345753
TI  - Restorative proctocolectomy and ileal pouch-anal anastomosis for right-sided
      colonic adenocarcinoma in familial adenomatous polyposis: an abdominal
      laparoscopic approach combined with transanal total mesorectal excision - a video
      vignette.

PMID- 29345754
TI  - Long-term follow-up after full-split liver transplantation and its applicability
      in the recent transplant era.
AB  - INTRODUCTION: Full-split liver transplantation (LTX) offers the possibility to
      expand the donor pool by utilization of one liver for two adults. The aim of our
      study was to analyze the long-term outcome in a large series and its
      applicability in the recent transplant era. METHODS: We performed a retrospective
      analysis of all full-split LTX from deceased donors (1999-2015). Additionally,
      the potential of full-split LTX was retrospectively analyzed in all whole organ
      LTX recipients between 2006 and 2015 (after introduction of the MELD allocation).
      RESULTS: We performed 44 full-split LTX, thereof 82% before introduction of the
      MELD-based allocation system in Germany. Analysis showed highly selected
      recipients (median MELD score 8 points) and organ data (median donor age 30
      years). 5- and 10-year patient survival rates after full-left and full-right LTX
      were 90.7%/90.7% and 85.2%/56.8% (P = .301), corresponding graft survival rates
      were 80.5%/80.5% in full-left grafts and 73.7%/36.8% in full-right graft (P =
      .198). CONCLUSION: In the past, in case of strict donor and recipient selection,
      full-split LTX was a feasible method with a good outcome. Due to introduction of
      the national waiting list with a patient-oriented allocation based on the MELD
      score in 2006, full-split LTX seems to be not any longer applicable.

PMID- 29345755
TI  - Expression of hepatic progenitor cell markers in acute cellular rejection of
      liver allografts-An immunohistochemical study.
AB  - BACKGROUND: Hepatic progenitor cells (HPC) are induced following liver injury to
      facilitate regeneration. Acute cellular rejection (ACR) is a common complication
      after liver transplantation as a result of immune-mediated liver injury. In this
      study, we characterized HPC phenotype in liver allograft biopsy with ACR. We also
      explored the correlation between expression HPC immunophenotype and
      clinicopathological parameters. METHODS: Forty-four liver allograft biopsies
      performed between 2008 and 2016 in a single center with histologically proven ACR
      were examined for immunohistochemical expression of HPC markers CK19 and Sox9.
      The number of positive-staining cells was assessed and correlated with
      clinicopathological features by statistical analysis. RESULTS: HPC phenotype
      expression as denoted by CK19 and Sox9 staining was detected in the liver tissue
      with ACR. The numbers of CK19+ and Sox9+ cells were positively correlated. A
      larger number of CK19+ cells were associated with higher serum aspartate
      aminotransferase (AST) level at biopsy. By histological rejection score, a larger
      number of Sox9+ cells were associated with a higher score of bile duct damage.
      CONCLUSION: Expression HPC markers were correlated with clinical and histological
      parameters in ACR. Expression of each individual marker may be more tightly
      associated with a particular component of the ACR process.

PMID- 29345756
TI  - Clinical Intentions of Antibiotics Prescribed Upon Discharge to Hospice Care.
AB  - OBJECTIVES: To better understand the clinical intentions for antibiotic
      prescribing upon discharge from acute care to hospice care. DESIGN: Retrospective
      cohort study. SETTING: Five hundred forty-four-bed academic, acute-care, tertiary
      referral hospital in Portland, Oregon. PARTICIPANTS: Adults (>=18) who received
      an outpatient prescription for antibiotics on discharge from an acute care
      hospital to hospice care between January 1, 2009 and December 31, 2011 (N = 149).
      MEASUREMENTS: We determined whether antibiotics were indicated for treatment of
      an active infection, palliative treatment, prophylaxis, or prescribed according
      to family or participant preference. RESULTS: Antibiotics were prescribed to
      17.6% (n = 149) of individuals discharged to hospice care over the 3-year study
      period. Antibiotics were most frequently prescribed for pneumonia (19.5%),
      urinary tract infections (18.9%), and gastrointestinal tract infections (17.0%).
      The explicit rationale for antibiotic prescription was documented for only 72
      prescriptions (45.3%). For 84 (52.8%) participants, antibiotics were used to
      treat an active infection in the hospital. Of prescriptions with a documented
      rationale, 37.5% indicated that the intent was curative, 26.4% prophylaxis, and
      22.2% to suppress an infection. For 19.4% of prescriptions, participants or their
      family members specifically wanted to be treated with antibiotics. Only 9.7% of
      prescriptions specifically indicated that antibiotics were prescribed for
      palliative reasons. CONCLUSION: Antibiotics were frequently prescribed for
      treatment of active infection in individuals discharged to hospice care. Further
      research is needed to document antibiotic benefits and risks and optimize
      medication management at the end of life.

PMID- 29345758
TI  - Continuous deacetylation of cephalosporins.
AB  - Continuous deacetylation of cephalosporin C, 7-aminocephalosporanic acid, and of
      2-methoxyethyl acetate in packed beds of an immobilized esterase is described by
      simple empirical equations relating conversion to space velocity and temperature.
      The choice of process conditions is discussed in relation to the effects of
      temperature on column efficiency, column life, growth of microbial contaminants,
      and the rates of thermal decomposition of the substrates. At the preferred
      temperature of 10 degrees C columns were operated continuously for one month with
      only small losses in efficiency.

PMID- 29345759
TI  - Continuous conversion of sucrose to fructose and gluconic acid by immobilized
      yeast cell multienzyme complex.
AB  - A multienzyme complex consisting of invertase, glucose oxidase, and catalase was
      reconstituted by binding glucose oxidase using concanavalin A (Con A) to the cell
      wall of Sacchararomyces cerevisiae, previously induced for maximal activities of
      invertase and catalase. The cell flocculate obtained was stabilized by entrapment
      in polyacrylamide using gamma irradiation at 100 kR. This complex showed a
      shortening of the lag period and enhancement in gluconic acid production as
      compared to a similar mixture of soluble enzymes. The efficacy of the multienzyme
      complex has been compared with that of mixed multienzyme system composed of
      individually immobilized enzymes. The immobilized multienzyme complex in a
      continuous-flow stirred-tank reactor system could be operated for continuous
      conversion of sucrose to fructose and gluconic acid. The reactor system did not
      show any loss in efficiency in a continuous operation over 20 days.

PMID- 29345757
TI  - Whole genome sequencing analysis for cancer genomics and precision medicine.
AB  - Explosive advances in next-generation sequencer (NGS) and computational analyses
      have enabled exploration of somatic protein-altered mutations in most cancer
      types, with coding mutation data intensively accumulated. However, there is
      limited information on somatic mutations in non-coding regions, including
      introns, regulatory elements and non-coding RNA. Structural variants and pathogen
      in cancer genomes remain widely unexplored. Whole genome sequencing (WGS)
      approaches can be used to comprehensively explore all types of genomic
      alterations in cancer and help us to better understand the whole landscape of
      driver mutations and mutational signatures in cancer genomes and elucidate the
      functional or clinical implications of these unexplored genomic regions and
      mutational signatures. This review describes recently developed technical
      approaches for cancer WGS and the future direction of cancer WGS, and discusses
      its utility and limitations as an analysis platform and for mutation
      interpretation for cancer genomics and cancer precision medicine. Taking into
      account the diversity of cancer genomes and phenotypes, interpretation of
      abundant mutation information from WGS, especially non-coding and structure
      variants, requires the analysis of large-scale WGS data integrated with RNA-Seq,
      epigenomics, immuno-genomic and clinic-pathological information.

PMID- 29345760
TI  - Application of temperature-sensitive mutants for single-cell protein production.
AB  - Cell-division-cycle, temperature-sensitive mutants of Saccharomyces cerevisiae
      were investigated as a means of altering the morphological characteristics and
      subsequent physical properties of single-cell protein (SCP). Strain 4471,
      harboring mutation cdc 4, formed a visible complex mass at the nonpermissive
      temperature, after being grown at 30 degrees C and then transferred to 37 degrees
      C for 8 hr. Microscopic observation showed that the mother cell was unable to
      complete the budding process at the nonpermissive temperature, which caused the
      cells to enlarge. Viscosity measurements were used to establish and characterize
      optimum morphological changes in the yeast. The Maximum increase in viscosity
      occurred when cells were incubated at 30 degrees C and then shifted to 37 degrees
      C for 8 hr. Strain 4471 exhibited yield stress, whereas A364A did not. Maximum
      change in yield stress occurred when cells were shifted from 30 to 37 degrees C
      for 8 hr. No significant loss of protein or RNA occurred in strain 4471, as
      compared to strain A364A, when incubated at the nonpermissive temperature.

PMID- 29345761
TI  - The Brazilian ethanol program.
AB  - Brazilian needs for petroleum as a primary energy source grew from 13.2% in 1940
      to 41.7% in 1977. This resulted in a much greater dependence on foreign sources
      and prompted the Government to initiate a detailed study of alternatives. The
      National Alcohol Program established in 1975 is just one of the options being
      examined. The National Energy Balance forecast shows that annual anhydrous
      alcohol consumption for automotive purposes should increase from 1.74 * 106 m3 to
      4.7 * 106 m3 in the period from 1978 to 1987. This paper presents the main
      objectives of the National Alcohol Program in the context of the overall Energy
      Program, points out the problems connected with alcohol production and
      utilization, and reviews the serious problems related to its distribution to the
      consuming centers. Finally, the indirect benefits resulting from the
      implementation of the National Alcohol Program are shown, underlining the saving
      of foreign currency, the substantial increase in employment opportunities, the
      reduction in regional and individual income discrepancies, and the expansion of
      capital goods production, together with the improvement of national technology in
      the agricultural and industrial sectors.

PMID- 29345762
TI  - Kinetic study on thermal stability of immobilized invertase.
AB  - The kinetic study of the thermal stability of three kinds of invertases: native,
      immobilized on porous glass covalently, and on ion-exchange resin ionically, has
      been carried out, measuring their enzymatic activity for sucrose hydrolysis.
      Thermal deactivations of all invertases obeyed first-order kinetics, being
      independent of substrate concentration, with kd and DeltaEd , DeltaSd * as shown
      in Tables I and II, respectively. Based on these parameter values, the effects of
      immobilization and pH at deactivation on the stability have been considered, and
      it was suggested that the ionic bond gives a more loosely deformed enzyme than
      the covalent bond.

PMID- 29345763
TI  - Modeling of rotating biological contactor systems.
AB  - An investigation of the rotating biological contractor (RBC) process variables to
      determine the efficiency of biological oxygen demand (BOD) removal is presented.
      Operating parameters including influent BOD content (<355 mg/liter), flow rate,
      disk surface area, hydraulic loading, disk rotational speed, liquid retention
      time, stage number, and wastewater temperature were evaluated. The BOD predictive
      model was developed using literature data with multiple regression analysis. This
      study shows that influent BOD concentration, hydraulic loading, stage number, and
      wastewater temperature are the most significant variables in predicting the RBC
      system performance. The model presently developed was verified by field data
      concerned with the treatment of both domestic and low-strength industrial
      wastewaters. Also, the results calculated by this model were compared to those
      obtained from Weng's model.

PMID- 29345764
TI  - Characteristics of immobilized invertase.
AB  - Five kinds of immobilized invertases (IMI)-covalently of porous glass and ion
      exchange resins and ionically on ion-exchange resins-have been prepared and their
      kinetic characteristics for sucrose hydrolysis, such as Km , K, pH profile, and
      thermal stability were studied. Comparing the values of Km and activation energy
      and the entropy of IMI with those of native invertase, it was concluded that the
      immobilization influences not binding but kinetic specificity. The effects of the
      immobilization method on thermal stability were also discussed.

PMID- 29345765
TI  - Batch- and continuous-culture studies of a methane-utilizing mixed culture.
AB  - A methane-utilizing mixed culture isolated from activated sludge by selective
      enrichment at 45 degrees C was found to consist of three interacting species: a
      methaneutilizing bacterium, a citrate-utilizing bacterium, and a methanol
      utilizing bacterium. All three species grew well at 45 degrees C. Three different
      stable mixed cultures were reconstituted by various combinations of these pure
      cultures. The nutritional requirements and substrate ranges for each pure culture
      were determined. The nutritional requirements and substrate ranges for each pure
      culture were determined. The saturation constant for the methane-utilizing
      bacterium on methane (K CH 4) and for the methanol-utilizing bacterium on
      methanol (K CH 3OH) were 1.73 * 10-6 M and 4.51 * 10-7 M, respectively. The
      volumetric mass transfer coefficient for methane (KL a) was determined to be 65.6
      hr-1 .

PMID- 29345766
TI  - Production of maltose and maltotriose from starch and pullulan by a immobilized
      multienzyme of pullulanase and beta-amylase.
AB  - Pullulanase was immobilized on tannic acid and TEAE-cellulose, and beta-amylase
      was covalently immobilized on p-aminobenzylcellulose. Both the immobilized
      enzymes showed similar properties in pH and temperature optima and heat
      stability. On passing the pullulan solution at high temperature (50 degrees C)
      through a column packed with immobilized pullulanase, only maltotriose was
      obtained for ten days and the half-life was about 15 days. In a continuous
      reaction using immobilized multienzyme, starch was completely converted into
      maltose at 50 degrees C and at a space velocity of 1.2, a comparative longer half
      life (20 days) was obtained. It was concluded that starch was smoothly converted
      into maltose with the aid of alpha-amylase contaminated in the immobilized
      pullulanase and the operational stability of the column increased with 2-5mM Ca2+
      .

PMID- 29345767
TI  - A quantitative description of the growth of Saccharomyces cerevisiae CBS 426 on a
      mixed substrate of glucose and ethanol.
AB  - Saccharomyces cerevisiae CBS 426 was grown aerobically in continuous culture with
      a mixture of glucose and ethanol as the carbon source. The flows of biomass,
      glucose, ethanol, oxygen, and carbon dioxide were measured. A model for growth
      with two substrates was derived. Application of this model to the above-mentioned
      system yielded values for YATP and P/O. The joint confidence regions for these
      parameters were calculated. The relevance to industrial production of bakers'
      yeast is discussed.

PMID- 29345768
TI  - Immobilized catalase-containing yeast cells: Preparation and enzymatic
      properties.
AB  - The cell of Saccharomyces cerevisiae previously induced for catalase (EC
      1.11.1.6) activity were immobilized by entrapment of intact cells in acrylamide
      polymerized by gamma irradiation (100 kR). Yeast cells showed an enhancement in
      catalase activity on entrapment, an effect similar to that observed on treatment
      with organic solvents like toluene. The cells pretreated with toluene, however,
      showed complete loss of catalase activity on entrapment. The entrapped enzyme
      exhibited a narrow pH optimum, reduced Km for H2 O2 , and a decrease in
      thermostability. The temperature optimum of catalase was also decreased from 60
      to 40 degrees C on immobilization. A tenfold decrease in the activation energy
      was also observed. The enzyme in the entrapped cells was, however, stable toward
      inactivation by gamma irradiation. Unlike the intact cells, the entrapped yeast
      cells did not have the ability to induce catalase.

PMID- 29345769
TI  - Substrate utilization kinetic model for biological treatment process.
AB  - The applicability of Contois' kinetic equation to aerobic and anaerobic
      treatments of organic wastes is investigated. A refractory coefficient to account
      for the nonbiodegradable portion of the organic substrates in the digester is
      incorporated into the kinetic equation. The kinetic equation is applied to the
      data for aerobic digestions of organic substrates and for anaerobic treatment of
      dairy wastes. They all show a very good fit of the kinetic equation to the data.
      Furthermore, the kinetic parameters and the refractory coefficients are shown to
      be independent of influent organic substrate concentration. This study confirms
      previous reports that the effluent quality of biological treatment systems for
      organic wastes depends on influent organic waste concentration. The effect of
      temperature on the kinetic parameters and the refractory coefficient for
      anaerobic treatment of sewage sludge are studied. It shows that the kinetic
      parameters vary with temperature, while the refractory coefficient remains fairly
      constant. Equations to predict biodegradable treatment efficiency and volumetric
      substrate utilization rate are also briefly discussed.

PMID- 29345770
TI  - Interspecific interactions in a methane-utilizing mixed culture.
AB  - A two-member methane-utilizing mixed culture of bacteria, formed by combining two
      pure cultures isolated from a naturally occurring methane-utilizing mixed
      culture, was studied in continuous culture. From the nutritional requirements and
      substrate ranges of the pure cultures, a mechanism for the interspecific
      interactions occurring in the mixed culture was proposed. Product formation
      kinetics were determined in continuous culture for each product involved in the
      proposed mechanism. From this proposed mechanism a mathematical model was derived
      based on simple material balance equations around a single-stage chemostat. The
      steady-state predictions of this model were compared to experimental results
      obtained from continuous-culture experiments with the two-member methane
      utilizing mixed culture. Interspecific interactions occurring in two-member
      methanol-utilizing and three-member methane-utilizing mixed cultures have also
      been discussed.

PMID- 29345771
TI  - Reply to Wang and Kan.

PMID- 29345772
TI  - Membrane responses induced by oligogalacturonides in suspension-cultured tobacco
      cells.

PMID- 29345773
TI  - Novel carbohydrate metabolism in the resurrection plant Craterostigma
      plantagineum.

PMID- 29345774
TI  - Rewiring Chemical Networks Based on Dynamic Dithioacetal and Disulfide Bonds.
AB  - The control of the connectivity between nodes of synthetic networks is still
      largely unexplored. To address this point we take advantage of a simple dynamic
      chemical system with two exchange levels that are mutually connected and can be
      activated simultaneously or sequentially. Dithioacetals and disulfides can be
      exchanged simultaneously under UV light in the presence of a sensitizer.
      Crossover reactions between both exchange processes produce a fully connected
      chemical network. On the other hand, the use of acid, base or UV light connects
      different nodes allowing network rewiring.

PMID- 29345775
TI  - Versatile Modes of Cooperative B-H Bond Activation Reactions in Ruthenium-Carbene
      Complexes: Addition, Ring-Opening and Insertion.
AB  - Cooperative B-H bond activation reactions with thio- and iminophosphoryl tethered
      ruthenium-carbene complexes are reported. The complexes show surprisingly
      different reactivities towards the commonly employed boranes CatBH, PinBH and BH3
      ?LB as a result of different modes of metal-ligand cooperation. Although the
      iminophosphoryl system allows for selective 1,2-addition of the B-H bond across
      the Ru=C double bond, the sulfur analogue only delivers the 1,2-addition product
      for CatBH, whereas activation of BH3 and PinBH lead to further insertion
      reactions in one or more sides of the Ru-C-P-S-ring. The different reactivities
      can be explained by the differences in the electronics of the carbene complexes
      and the phosphoryl tether and by the Lewis acidities of the boranes. DFT
      calculations show that the mechanism of the reactions either proceeds by an
      addition across the Ru=C bond with different regioselectivities or across the Ru
      S linkage.

PMID- 29345776
TI  - Allyl Isothiocyanate Ameliorates Obesity by Inhibiting Galectin-12.
AB  - SCOPE: The aim of this study is to investigate the signaling pathways by which
      allyl isothiocyanate (AITC) reduces adipocyte differentiation and the efficacy of
      AITC in suppressing galectin-12 levels as a therapeutic for high fat diet (HFD)
      induced obesity. METHODS AND RESULTS: AITC presents anti-adipogenic effects on
      3T3-L1 cells by decreasing lipid droplet accumulation in a dose-dependent manner.
      AITC suppresses 3T3-L1 differentiation into adipocytes by decreasing galectin-12
      expression and by downregulating key adipogenic transcription factors. AITC
      influences the expression of 3T3-L1 pre-adipocytes by modulating adipokine
      expression (leptin and resistin) and by regulating the protein kinase B
      (PKB/Akt)/cAMP response element-binding protein (CREB) pathway. In HFD-fed mice,
      oral administration of AITC reduces the body weight, accumulation of lipid
      droplets in the liver, and white adipocyte size. CONCLUSION: In summary, the
      results indicate that AITC inhibits adipocyte differentiation by suppressing
      galectin-12 levels in 3T3L1 cells and has antiobesity effects in HFD-fed mice.

PMID- 29345777
TI  - The occurrence and prevention of ethanol fermentation in high-dry-matter grass
      silage.
AB  - Ethanol is a common, usually minor fermentation product in ensiled forages, the
      major product being lactic acid. Occasionally, high levels of ethanol are found
      in silages. The aim of this study was to determine the incidence of high-dry
      matter (DM) grass silages containing ethanol as the main fermentation product
      (ethanol silages), to describe the fermentation process in such silages and to
      determine the effect of grass maceration prior to wilting and addition of a
      bacterial inoculant containing Lactobacillus plantarum and Enterococcus faecium
      strains on fermentation. Twenty-one laboratory silages produced between 1993 and
      1995, 21 farm silages produced between 1980 and 1989 and 36 farm silages produced
      in 1995 (all produced without additive) were examined for pH and chemical
      composition. Dry matter (DM) loss during ensilage was determined for the
      laboratory silages only. Four laboratory silages were identified as ethanol
      silages. Mean concentrations of ethanol, lactic acid and acetic acid were 48.1,
      15.5 and 6.0 g kg-1 DM respectively. In the silages that contained lactic acid as
      the main fermentation product (lactic acid silages) these values were 7.7, 45.5
      and 15.1 g kg-1 DM. Mean DM loss and pH were 62.8 g kg-1 DM and 5.32 respectively
      for ethanol silages and 24.4 g kg-1 DM and 4.69 for lactic acid silages. There
      was no difference between ethanol silages and lactic acid silages in the mean
      concentration of ammonia-N (94 g kg-1 total N), and butyric acid was not detected
      (<0.2 g kg-1 DM), indicating that both types of silages were well preserved.
      Analysis of the composition of the grass at ensiling showed a positive
      correlation between the concentration of soluble carbohydrates and the
      development into ethanol silage. Analysis of the farm silages indicated that 29%
      of the silages produced between 1980 and 1989 and 14% of those produced in 1995
      were ethanol silages. Maceration prior to wilting and addition of silage
      inoculant improved lactic acid fermentation and prevented high ethanol levels.
      The micro-organisms responsible for ethanol fermentation as well as the
      implications of feeding ethanol silages to livestock remain to be resolved. (c)
      2000 Society of Chemical Industry.

PMID- 29345778
TI  - First confirmation in red wine of products resulting from direct anthocyanin
      tannin reactions.
AB  - Analysis of wine fractions before and after thiolysis confirmed the occurrence in
      red wine of direct reactions between anthocyanins and tannins established earlier
      in model solutions. Results showed the presence of two types of structures
      differing in the linkage position of the anthocyanin moiety. On one hand,
      detection of malvidin-3-glucoside (Mv3g) among thiolysis products revealed the
      presence of anthocyanin-derived pigments in which Mv3g is linked by its C-6 or C
      8 top. On the other hand, LC/MS analysis allowed the detection of two derivatives
      tentatively identified as flavenes or a bicyclic condensation products yielded by
      the reaction of a flavanol monomer (C-6 or C-8 top) with malvidin-3-glucoside (C
      4 position). The presence of the corresponding benzylthioethers after thiolysis
      of the polymeric fractions confirmed that procyanidins are similarly involved in
      the latter reaction. Besides, MS also allowed the detection of new
      benzylthioethers of catechin derivatives released after thiolysis of the wine
      fractions, indicating that in addition to the postulated processes other types of
      reactions take place in wines. (c) 2000 Society of Chemical Industry.

PMID- 29345779
TI  - Kinetics of flavour and aroma changes in thermally processed cupuacu (Theobroma
      grandiflorum) pulp.
AB  - Changes in 'fresh' and 'cooked-notes' during thermal treatment of cupuacu
      (Theobroma grandiflorum) pulp were evaluated and modelled. Isothermal experiments
      in the temperature range of 70-98  degrees C were carried out and a non-linear
      regression was performed to all data to estimate kinetic parameters. 'Fresh' and
      'cooked-notes' change followed simple first-order (Ea = 78-82 kJ.mol-1 , z = 30
      31  degrees C) and reversible first order (Ea = 80-85 kJ.mol-1 ) kinetics,
      respectively. Although 'cooked-notes' were linearly correlated with 'fresh-notes'
      (R2  = 0.99), the former was a better indicator for quality degradation. These
      results are useful to design pasteurisation processes while minimising sensory
      changes. (c) 2000 Society of Chemical Industry.

PMID- 29345780
TI  - Influence of intramuscular fat content on lipid composition, sensory qualities
      and consumer acceptability of cured cooked ham.
AB  - The present study is part of a project which aims to examine the influence of
      intramuscular fat (IMF) content on the sensory attributes and consumer
      acceptability of pork. An experiment was conducted to evaluate the influence of
      IMF level in muscle semimembranosus (SM) on the composition of its lipid fraction
      and on the sensory qualities and consumer acceptability of cured cooked hams.
      Thirty-two carcasses were selected 24 h after slaughter from 125 Duroc * Landrace
      castrated male pigs showing large variability in SM muscle IMF content and were
      assigned to four IMF groups: <=2%, 2-3%, 3-4% and >4%. Cured cooked ham slices
      were evaluated by a trained expert panel of 12 members and by a group of 56
      consumers. Results from lipid analyses indicate that (i) an increase in IMF
      content was almost entirely reflected by an increase in the triglyceride content
      of the muscle and (ii) higher IMF levels were associated with higher free fatty
      acid and monoglyceride and lower cholesterol levels. The sensory evaluation of
      marbling significantly increased with IMF level, whereas other sensory qualities
      were unaffected. High IMF levels significantly depreciated the consumer
      perception of fat, aspect, taste and smell of ham slices. Overall, slices with
      the highest IMF levels got the least favourable rating by consumers. The present
      study indicates that increased IMF levels in muscle semimembranosus do not have
      significant effects on the sensory attributes of cured cooked hams, apart from
      the perception of marbling. However, high IMF levels have detrimental effects on
      the acceptability by consumers. (c) 2000 Society of Chemical Industry.

PMID- 29345781
TI  - The yield and carcass chemical composition of impala (Aepyceros melampus), a
      southern African antelope species.
AB  - This investigation analyses the commercial carcass yields and chemical
      composition of impala (Aepyceros melampus). The potential of this species for the
      export market is also discussed. Impala rams (eight) and ewes (eight) cropped
      commercially in Zimbabwe were found to have a similar dressout proportion (580 g
      kg-1 ), although the males had a heavier live weight (49.4 +/- 4.606 kg) than the
      females (33.5 +/- 3.417 kg). Sexual dimorphism was shown, with the males having
      significantly (p < 0.01) heavier necks (69 +/- 5.47 g kg-1 ) and forequarters
      (279 +/- 3.79 g kg-1 ) than the females (51 +/- 1.70 and 259 +/- 2.15 g kg-1
      respectively) when expressed as a proportion of cold carcass weight (27.6 +/-
      2.551 and 19.0 +/- 1.960 kg for males and females respectively). No sexual
      effects (p > 0.2) were found in the mean chemical proximate composition of the 9
      10-11 rib cut for the moisture (724.0 +/- 14.00 g kg-1 pooled sample), protein
      (238.3 +/- 7.46 g kg-1 pooled sample) and ash (21.2 +/- 3.74 g kg-1 pooled
      sample) contents. The females had a statistically higher (p = 0.0197) mean total
      lipid content (33.9 +/- 1.705 g kg-1 ) than the males (24.5 +/- 3.171 g kg-1 ).
      This investigation occurred at the end of the impala rut season, a period when
      the rams not only consume less feed but also expend more energy owing to
      strenuous activities in fighting for and maintaining a harem. (c) 2000 Society of
      Chemical Industry.

PMID- 29345782
TI  - Comparison of the expansion ability of fermented maize flour and cassava starch
      during baking.
AB  - The modifications occurring during the fermentation (at 20 or 35  degrees C) and
      drying (under the sun or in an oven at 40  degrees C) of maize flour (ogi) and
      cassava starch along with their expansion ability during baking were
      characterised and compared. A high temperature accelerated the fermentation but
      favoured lactic acid synthesis for maize ogi and butyric acid for cassava starch.
      The increase in acidity was higher for maize, but dried maize ogi did not
      evidence any expansion ability whatever the experimental conditions. Cassava
      starch that had been fermented at 20  degrees C then sun-dried presented the
      highest expansion ability. It was associated with low paste viscosities and high
      swelling and solubilisation values. When the fermentation was carried out at 35 
      degrees C, an annealing of cassava starch occurred that delayed starch
      gelatinisation and which could be involved in its lower baking expansion ability.
      (c) 2000 Society of Chemical Industry.

PMID- 29345783
TI  - Nutritional quality of complementary food prepared from unmalted and malted maize
      fortified with cowpea using extrusion cooking.
AB  - The nutritional quality of extruded unmalted or malted maize fortified with
      cowpea as complementary food was assessed based on its proximate analysis, amino
      acid composition and results from rat feeding with the blends. Results indicated
      a slight decrease and increase in protein content due to malting and extrusion
      respectively. The changes in fat, crude fibre and ash content were not
      significant. The blends were a good source of energy, ranging from 1831 to 2045
      kJ per 100 g. Extrusion significantly increased the amino acid content of the
      blends, while malting had a varied effect on each of the amino acids. There was
      no significant difference in the protein efficiency ratio (PER), net protein
      ratio (NPR) and weight gain of rats fed the blends when compared with the control
      (casein diet). The present study shows that malting improved the nutritional
      quality of the blends. Rats fed the casein diet had higher values for total
      digestibility (TD) and net protein utilisation (NPU). There was no significant
      difference (P > 0.05) in the internal organ weights of rats fed all blends except
      the protein-free diet. (c) 2000 Society of Chemical Industry.

PMID- 29345784
TI  - Interaction between Maillard reaction products and lipid oxidation in starch
      based model systems.
AB  - The effect of Maillard reaction products (MRPs) on the kinetics of lipid
      oxidation in intermediate-moisture model systems containing pregelatinised
      starch, glucose, lysine and soybean oil has been studied. The samples, either
      containing all components or excluding one or more of them, were heated at 100 
      degrees C for different times. Lipid oxidation and browning indices were measured
      and the results confirmed the ability of MRPs to retard peroxide formation. Under
      the conditions adopted, the rate of the Maillard reaction was increased by the
      presence of the oil and its oxidation products. The antioxidant action of MRPs
      was also evaluated using a peroxide-scavenging test based on crocin bleaching.
      The results demonstrated that antioxidant activity developed with increased
      browning of the samples. (c) 2000 Society of Chemical Industry.

PMID- 29345785
TI  - Sequential hydrolysis of swine carcass samples and determination of amino acid
      concentrations using pre-column derivatization with phenyl isothiocyanate.
AB  - Comparing amino acid (AA) retention levels in pig carcass to true ileal
      digestible AA intake provides an estimate of the marginal efficiency of AA
      utilization. Accurate analysis of AA levels in the carcass samples is critical.
      However, the standard 24 h of hydrolysis does not always provide maximum AA
      values. A study was carried out to investigate the effect of hydrolysis time on
      AA measurements in pig carcass. Correction factors to standardize AA levels to 24
      h of hydrolysis were also determined. Ground carcass samples were hydrolysed with
      6 mol litre-1 hydrochloric acid (HCl) in a 110  degrees C oven for nine different
      time periods. Pre-column derivatization with phenyl isothiocyanate (PITC) was
      used to determine AA concentrations in all of the samples. Hydrolysis time
      significantly affected (P < 0.001) AA levels. The highest levels (P > 0.05) of
      valine, isoleucine, serine, glycine, threonine, alanine, arginine, proline,
      histidine and phenylalanine were not observed with 24 h hydrolysis. Therefore,
      correction factors and sequential hydrolysis curves are important for these amino
      acids. In conclusion, the effect of hydrolysis time should be considered in amino
      acids analysis. (c) 2000 Society of Chemical Industry.

PMID- 29345786
TI  - Existing and potential applications of ultraviolet light in the food industry - a
      critical review.
AB  - Short-wave ultraviolet light (UVC, 254 nm) can reduce dramatically the microbial
      load in air or on hard surfaces free from food residues, and can eliminate
      pathogens from potable water filtered to remove organic residues and 'clumps' of
      bacteria. More recently, approval of the Food and Drug Administration (USA) has
      been sought for a system for the destruction of pathogenic bacteria in fruit
      juices using UVC, and the same approach could perhaps be applied to remove
      spoilage organisms from cider or wines. In contrast, long-wave UV light (UVA,
      >320 nm) has limited microbiocidal properties, and for practical applications its
      effectiveness has to be enhanced by the presence of photosensitive compounds (eg
      furocoumarins) that will diffuse into a microbial cell prior to irradiation. The
      penetration of UVA into water is better than that of UVC, and its bacteriocidal
      action in the presence of photosensitisers can be rapid. However, pure
      furocoumarins are expensive and their addition to foodstuffs might be questioned
      on safety grounds. (c) 2000 Society of Chemical Industry.

PMID- 29345787
TI  - Development and application of soy-protein films to reduce fat intake in deep
      fried foods.
AB  - A soy protein film coating was developed and evaluated to reduce fat transfer in
      deep-fried foods during frying. Soy protein isolate solutions (10% SPI) with
      0.05% gellan gum as plasticizer cooled after being held at 80  degrees C for 20
      min provided suitable films. There was a significant fat reduction (55.12 (+/
      6.03)%db) between fried uncoated and coated discs of doughnut mix. The same films
      were used on potato fries. Some panellists observed a slight difference between
      the coated and uncoated fries but many preferred the coated fries over the
      uncoated ones. Penetration test on potato fries showed no significant difference
      between the texture of coated (SPI with gellan gum) and the uncoated fried
      samples. A solution of 10% SPI with 0.05% gellan gum is recommended for coating
      foods to reduce fat intake during deep-fat frying. (c) 2000 Society of Chemical
      Industry.

PMID- 29345788
TI  - Activities of phospholipases A and lysophospholipases in glycolytic and oxidative
      skeletal muscles in the rabbit.
AB  - Oxidative muscles contain more free fatty acids than glycolytic muscles, which
      could explain in part their higher sensitivity to oxidation. These fatty acids
      are partly the result of phospholipid hydrolysis catalysed by phospholipases A
      and lysophospholipases. Up to now, very little is known on the activities of
      these enzymes in skeletal muscles. This study deals with the activities of
      phospholipases A and lysophospholipases in five rabbit muscles covering a large
      range of metabolic types (oxidative Soleus and Semimembranosus proprius muscles,
      glycolytic Psoas major and Longissimus lumborum muscles and intermediate
      Gastrocnemius laterale muscle). The results showed that (a) phospholipases A and
      lysophospholipases had maximal activity at pH 8-9; (b) phospholipases A and
      lysophospholipases retained more than 50% of their maximal activity at pH 5.5-6,
      the ultimate pH of muscles; (c) lysophospholipases exhibited a higher activity
      than phospholipases A (4-7-fold higher in the oxidative muscles, 11-fold higher
      in the intermediate muscle and 18-23-fold higher in the glycolytic muscles); and
      (d) phospholipase A and lysophospholipase activities were higher in oxidative
      muscles than in glycolytic muscles (10-25-fold higher for phospholipases A and 4
      5-fold higher for lysophospholipases). Thus oxidative muscles have a higher
      potential activity for post-mortem hydrolysis of phospholipids. (c) 2000 Society
      of Chemical Industry.

PMID- 29345789
TI  - A mathematical model for colour loss in paprikas containing differing proportions
      of seed.
AB  - In this paper a general kinetic model for predicting the colour of paprikas with
      differing proportions of seed as a function of the storage conditions is
      developed. We apply this model to study the effect of time and storage conditions
      on colour loss in paprikas made from the same pepper variety, Ocal, but with
      differing proportions of seed. The agreement between the experimental colour data
      for this paprika and the results predicted by the mathematical model is very
      good. Both the model and the experimental data show that the rate of colour loss
      decreases with increasing proportion of seed, and after a determined inversion
      time the samples with the lowest initial colour values actually show the highest
      values. Likewise, the experimental data show that for a given proportion of seed
      the colour loss decreases as the storage relative humidity increases. (c) 2000
      Society of Chemical Industry.

PMID- 29345790
TI  - Evaluating two kinds of centrifuged virgin oils arising from continuous olive
      processing.
AB  - Oils extracted from olive pastes by the direct centrifugation mode were compared
      with the homologous oils produced by the indirect centrifugation (after
      percolation) mode. The former were characterised by: (i) higher contents of total
      phenols, o-diphenols, hydroxytyrosol, hydroxytyrosol-aglycons, total volatiles,
      trans-2-hexanal and other pleasant volatiles, total tocopherols, total sterols
      and waxes; (ii) lower contents of triterpene dialcohols, aliphatic and triterpene
      alcohols, chlorophylls and pheophytins; (iii) lower values of integral colour
      index; (iv) higher values of turbidity, campesterol/stigmasterol ratio, 1,2
      diglycerides/1,3-diglycerides ratio, oxidative stability and overall quality
      indices; and (v) higher sensory score. Stigmastadienes and trans-isomer C18 fatty
      acids were always not detected. The average oil outputs of the two centrifugation
      extraction procedures were comparable, as confirmed by similar overall oil
      amounts found in the by-products. (c) 2000 Society of Chemical Industry.

PMID- 29345791
TI  - Characterisation of peptides in silages made from perennial ryegrass with
      different silage additives.
AB  - The effects of applying either formic acid (5.4 g kg-1 ), a mixture of formic
      acid (2.7 g kg-1 ) and formaldehyde (1.5 g kg-1 , 81 g kg-1 herbage crude
      protein) or two concentrations of a cysteine peptidase inhibitor, cystamine (5 or
      50 g kg-1 ), to perennial ryegrass (Lolium perenne) on the nitrogen (N)
      distribution of the resulting silages were investigated, with emphasis on changes
      in concentration, composition and molecular weight of silage peptides. Herbage
      (156 g dry matter kg-1 and 141 g water-soluble carbohydrate kg-1 dry matter) was
      ensiled in triplicate in laboratory silos for 100 days. Formic acid and the
      formic acid/formaldehyde mixture reduced soluble non-protein N and ammonia N
      concentrations (P < 0.01); in addition, formic acid increased peptide N
      concentrations (P < 0.05). Cystamine at 50 g kg-1 reduced ammonia N
      concentrations (P < 0.01) and increased peptide N concentrations (P < 0.05), but
      when applied at 5 g kg-1 had little effect. Gel filtration of silage extracts on
      Sephadex G-25 suggested that a small proportion (0.06-0.11 g kg-1 peptide N) of
      silage peptides had a chain length of 7-9 amino acids, but remaining peptides
      were smaller with chain lengths of 2-6 amino acid residues. Amino acid analysis
      of silage peptides indicated that additive treatment had little effect on peptide
      amino acid composition but that peptides with a chain length of 7-9 amino acids
      contained lower proportions of isoleucine and arginine. (c) 2000 Society of
      Chemical Industry.

PMID- 29345792
TI  - Location of and post-mortem changes in some cytoskeletal proteins in pork and cod
      muscle.
AB  - The cytoskeletal proteins actin, nebulin, spectrin, desmin, vinculin and talin
      were labelled immunohistochemically in sections of muscle from commercially
      available pigs and cod (Gadus morhua) taken pre-rigor and from samples stored for
      several days. Actin, nebulin and spectrin gave similar labelling patterns in both
      pork and cod muscle which remained the same in stored samples. Desmin was
      intensely labelled at the cell boundaries and within the body of the cells in
      both pork and cod in the initial and the stored samples. Vinculin was readily
      labelled in pork muscle but showed only diffuse labelling in fish. Labelling for
      talin in pork muscle was intense at the sarcolemma but was not present in samples
      stored for 4 days. In contrast, the label for talin was concentrated at the
      myotendinous junction of the cod muscle throughout the storage period. These are
      the first reports of the detection and location of spectrin and vinculin in fish
      muscle and of the location of talin. The results are discussed in terms of muscle
      structure, function and post-mortem tenderisation. (c) 2000 Society of Chemical
      Industry.

PMID- 29345793
TI  - Characteristics of nixtamalised maize flours produced with the use of microwave
      heating during alkaline cooking.
AB  - Whole, ground and abrasively dehulled grains from both normal (H-34 and H-34) and
      quality protein (QPM and QPMa) maize were mixed with water contents of 70, 95 and
      100 g kg-1 and calcium hydroxide concentrations of 0.0, 0.3, 0.5 and 2.0 g kg-1
      and heated (operating frequency 2.450 MHz, high-power setting) for 10, 15 and 20
      min in a commercial microwave oven. The cooked grain was then oven dried and
      milled to obtain nixtamalised maize flour (NMF). The protein contents and test
      weights of QPM were higher than for the normal hybrids. The highest yields of
      masa and tortillas were found for the normal hybrids, and these samples did not
      show significant differences, as compared with the commercial nixtamalised flour
      (CNMF) used as control, with respect to masa firmness and adhesiveness and
      tortilla tensile strength. The cutting force of tortillas from hybrid H-30 and
      QPM did not show significant differences from the control. The highest values of
      tortilla rollability were found for the control followed by hybrid H-34. The
      values of residual cooking liquor for microwave-heated samples were lower than
      for the control. Ground or dehulled maize grain gave sticky masa and poor
      mechinical characteristics. Tortillas from whole grain showed good
      characteristics of texture and consistency of masa, and the tortillas were
      subjectively similar in colour, flavour and rollability to the tortillas prepared
      with CNMF. These results indicate a potential use of microwave energy to produce
      NMF for tortillas and derivatives. (c) 2000 Society of Chemical Industry.

PMID- 29345794
TI  - A modified laboratory canning protocol for quality evaluation of dry bean
      (Phaseolus vulgaris L).
AB  - The effects of calcium (Ca2+ ) level in the soak water, blanch water and brine,
      blanching temperature, and total seed solids on dry bean canning quality were
      investigated to optimise a laboratory canning protocol. A linear increase in the
      Ca2+ level of soak water, blanch water and brine resulted in a linear decrease in
      hydration coefficient and percent washed drained weight but a linear increase in
      texture. Low Ca2+ level (10 mg kg-1 ) reduced the hydration time for dry bean
      seed from 14 to 1 h. Blanching temperatures of 50, 70 and 88  degrees C had non
      significant effects on canning quality traits. Blanching for 30 min at 70 
      degrees C for black bean or at 88  degrees C for navy bean and pinto bean
      resulted in percent washed drained weight >= 60, as required by the Canada
      Agricultural Products Standards Act. Seed solids levels of 95-97 g per 300 * 407
      (14 fl oz) can were sufficient to attain a percent washed drained weight of 60.
      It was confirmed that the thermal processing conditions (115.6  degrees C retort
      temperature, 45 min) used in this study were sufficient to achieve commercial
      sterility. The optimised lab protocol for evaluation of the canning quality of
      dry bean breeding lines is as follows. Seed containing 95 g of solids for pinto
      bean, 96 g for navy bean and 97 g for black bean is soaked in water for 30 min at
      20  degrees C and blanched for 30 min at 70  degrees C for black bean and 88 
      degrees C for navy bean and pinto bean in water containing 10 mg kg-1 of Ca2+ .
      The seed is then transferred to a 300 * 407 can, filled with brine containing 10
      mg kg-1 of Ca2+ , 1.3% (w/v) of NaCl and 1.6% (w/v) of sugar. The can is then
      sealed, processed in steam at 115.6  degrees C for 45 min and cooled at 20 
      degrees C for 20 min. Cans are stored for at least 2 weeks prior to quality
      evaluation of the canned product. Canning of dry bean seed according to this
      protocol results in precise estimation of canning quality traits, particularly
      percent washed drained weight. (c) 2000 Society of Chemical Industry.

PMID- 29345795
TI  - Combined effect of high pressure, temperature and holding time on
      polyphenoloxidase and peroxidase activity in banana (Musa acuminata).
AB  - Polyphenoloxidase and peroxidase enzyme activities were evaluated following
      combined pressure, temperature and holding time treatment in banana (Musa
      acuminata). Using pressures of up to 110 MPa, temperatures of up to 70  degrees C
      and holding times of up to 25 min, based on a 23 central composite design, the
      interactive effects were found to significantly influence the activity of both
      enzymes in prepared banana pulp. Temperature and pressure were found to influence
      the inactivation of polyphenoloxidase separately, while temperature, pressure and
      holding time were found to influence the loss of peroxidase in the banana,
      although no significant interactive effects were found. The reduction in
      polyphenoloxidase activity was found to be less influenced by the combined
      treatment than peroxidase activity, thought to be due to solubilisation of the
      enzyme and effects of the soluble solids content. (c) 2000 Society of Chemical
      Industry.

PMID- 29345796
TI  - Physicochemical and rheological characteristics of commercial nixtamalised
      Mexican maize flours for tortillas.
AB  - Three commercial nixtamalised Mexican maize flours (CNMFs) designated HI-A, HI-B
      and HI-C were evaluated in this work. For each brand, four samples corresponding
      to four consecutive months of production were evaluated. Tortillas prepared by
      the traditional process of nixtamalisation were used as the control. The maize
      flours and their respective tortillas showed variations between samples in their
      physical, chemical and rheological parameters. The three commercial maize flours
      incorporated additives and preservatives. The moisture content, colour, pH,
      subjective water absorption capacity, water solubility index, water absorption
      index and swelling capacity of flours showed strong differences between the three
      CNMFs with respect to the chemical analysis. Important differences in the
      protein, calcium and amylose contents were observed. Tortillas from CNMFs had a
      blander maize flavour, less desirable texture and staled more rapidly than
      traditional tortillas. Some modifications are required in the current Official
      Mexican Quality Standard, principally in the appropriate selection of additives
      and levels used in the preparation of CNMFs. (c) 2000 Society of Chemical
      Industry.

PMID- 29345797
TI  - Changes in the carotenoid content of apricot (Prunus armeniaca, var Bergeron)
      during enzymatic browning: beta-carotene inhibition of chlorogenic acid
      degradation.
AB  - Considering the numerous beneficial effects in human health ascribed to
      carotenoids, studies were performed to investigate the modification of carotenoid
      amount and composition during apricot enzymatic browning. First works on bruised
      apricot purees have shown a trans-beta-carotene isomerisation (20%) induced by
      enzymatic browning. To clarify this isomerisation, oxidation of chlorogenic acid
      in presence of trans-beta-carotene, catalysed by purified apricot
      polyphenoloxidase (PPO), was followed by HPLC and polarography. Isomerisation
      rate of trans-beta-carotene in its cis isomer was found to increase with
      chlorogenic acid concentration. Moreover, trans-beta-carotene was shown to be a
      potent inhibitor of phenol degradation. This inhibition was partially ascribed to
      PPO inhibition (non-competitive inhibitor towards phenol with an apparent Ki
      close to 0.5 mM, a mixed type inhibitor towards oxygen with an apparent Ki close
      to 0.15 mM). The additional inhibition was explained by non-enzymatic reactions
      involving trans-beta-carotene and chlorogenic acid o-quinones and leading to
      phenol regeneration and carotene isomerisation. (c) 2000 Society of Chemical
      Industry.

PMID- 29345798
TI  - Clinical impact of pharmacokinetic interactions between the HCV protease
      inhibitor simeprevir and frequently used concomitant medications.
AB  - AIMS: Direct-acting antiviral agents (DAAs) for the treatment of hepatitis C
      (HCV) can be associated with drug-drug interactions (DDIs) with concomitant
      medications. The practical clinical implications of such DDIs are poorly
      understood. We assessed the clinical impact of possible pharmacokinetic (PK)
      interactions between simeprevir and frequently prescribed concomitant
      medications. METHODS: This post hoc analysis pooled data from nine studies which
      evaluated simeprevir (SMV)-based interferon-free HCV treatment. Three classes of
      frequently used concomitant medications of interest (CMOIs) were analysed
      [antihypertensive drugs (AHDs), anxiolytic drugs (AXDs) and lipid-lowering drugs
      (LLDs)] and categorized as amber or green according to their DDI potential with
      SMV (green: no DDIs; amber: potential/known PK interactions). Concomitant
      medications not recommended to be coadministered with SMV were not included. The
      composite primary endpoint was defined as the frequency of either
      discontinuation, interruption or dose modification of the CMOI during 12 weeks of
      SMV treatment. RESULTS: Few patients met the composite endpoint in the various
      subgroups. Patients on amber CMOIs tended to experience CMOI modification more
      often (13.4-19.4%) than those on green CMOIs (3.1-10.8%). There was no difference
      in the frequency of adverse events between patients taking green and those taking
      amber CMOIs. CONCLUSIONS: In this large pooled analysis, coadministration of the
      evaluated commonly prescribed medications with known or potential PK interactions
      with SMV was manageable and resulted in few adjustments of concomitant
      medications. Our method could serve as a blueprint for the evaluation of the
      impact of DDIs.

PMID- 29345799
TI  - Self-criticism self-report measures: Systematic review.
AB  - PURPOSE: Self-criticism is a transdiagnostic process that has been attracting
      research and clinical interest. The accurate measurement of this construct is
      therefore crucial; however, there are currently numerous measures of self
      criticism and no guidelines about which to use in different contexts. This
      systematic review evaluated the measurement properties of self-report
      questionnaires of self-criticism. METHODS: OvidSP and Web of Science were used to
      search through multiple databases, and an initial grey literature search was
      completed. Studies were included when the main focus was to evaluate the
      measurement properties of English version of scales or subscales that aimed to
      measure self-criticism in an adult population. Both the methodological quality of
      included studies and the specific measurement properties were evaluated; these
      ratings were then combined into a best evidence synthesis. RESULTS: Five scales
      and five subscales were identified, described in 16 papers. The scales were
      designed to measure different types of self-criticism including trait or
      repetitive self-criticism and self-criticism in response to difficult situations
      or as a mood regulation strategy. The majority of included studies were either
      rated as having poor methodological quality, or were given indeterminate or
      negative ratings for the measurement properties they reported. Questionnaire
      content varied depending on how the authors conceptualized self-criticism. Issues
      were also highlighted in relation to the checklist used to rate methodological
      quality. CONCLUSIONS: Tentative recommendations were made about two measures of
      self-criticism based on existing evidence; future research is required.
      Furthermore, questionnaire choice should be based on the type of self-criticism
      being assessed. PRACTITIONER POINTS: Self-criticism has been associated with a
      range of clinical difficulties including depression and eating disorders and is
      increasingly the focus of research, including treatment studies directly
      targeting self-criticism. Since different researchers have conceptualized self
      criticism differently, a number of self-criticism self-report questionnaires have
      been developed that vary in terms of design, structure, and content. This
      systematic review identified and evaluated the measurement properties of self
      report questionnaires of self-criticism and makes tentative recommendations about
      their use in clinical and research settings and areas for future research.

PMID- 29345800
TI  - Haplotype-based genotyping-by-sequencing in oat genome research.
AB  - In a de novo genotyping-by-sequencing (GBS) analysis of short, 64-base tag-level
      haplotypes in 4657 accessions of cultivated oat, we discovered 164741 tag-level
      (TL) genetic variants containing 241224 SNPs. From this, the marker density of an
      oat consensus map was increased by the addition of more than 70000 loci. The
      mapped TL genotypes of a 635-line diversity panel were used to infer chromosome
      level (CL) haplotype maps. These maps revealed differences in the number and size
      of haplotype blocks, as well as differences in haplotype diversity between
      chromosomes and subsets of the diversity panel. We then explored potential
      benefits of SNP vs. TL vs. CL GBS variants for mapping, high-resolution genome
      analysis and genomic selection in oats. A combined genome-wide association study
      (GWAS) of heading date from multiple locations using both TL haplotypes and
      individual SNP markers identified 184 significant associations. A comparative
      GWAS using TL haplotypes, CL haplotype blocks and their combinations demonstrated
      the superiority of using TL haplotype markers. Using a principal component-based
      genome-wide scan, genomic regions containing signatures of selection were
      identified. These regions may contain genes that are responsible for the local
      adaptation of oats to Northern American conditions. Genomic selection for heading
      date using TL haplotypes or SNP markers gave comparable and promising prediction
      accuracies of up to r = 0.74. Genomic selection carried out in an independent
      calibration and test population for heading date gave promising prediction
      accuracies that ranged between r = 0.42 and 0.67. In conclusion, TL haplotype GBS
      derived markers facilitate genome analysis and genomic selection in oat.

PMID- 29345802
TI  - The EAA International Quality Control Programme for Y-Chromosomal Microdeletions.

PMID- 29345801
TI  - Individual psychological therapy in an acute inpatient setting: Service user and
      psychologist perspectives.
AB  - OBJECTIVES: The acute inpatient setting poses potential challenges to delivering
      one-to-one psychological therapy; however, there is little research on the
      experiences of both receiving and delivering therapies in this environment. This
      qualitative study aimed to explore service users' and psychologists' experiences
      of undertaking individual therapy in acute inpatient units. It focused on the
      relationship between service users and psychologists, what service users found
      helpful or unhelpful, and how psychologists attempted to overcome any challenges
      in delivering therapy. DESIGN: The study used a qualitative, interview-based
      design. METHODS: Eight service users and the six psychologists they worked with
      were recruited from four acute inpatient wards. They participated in individual
      semi-structured interviews eliciting their perspectives on the therapy. Service
      users' and psychologists' transcripts were analysed together using Braun and
      Clarke's (2006, Qualitative Research in Psychology, 3, 77) method of thematic
      analysis. RESULTS: The accounts highlighted the importance of forming a 'human'
      relationship - particularly within the context of the inpatient environment - as
      a basis for therapeutic work. Psychological therapy provided valued opportunities
      for meaning-making. To overcome the challenges of acute mental health crisis and
      environmental constraints, psychologists needed to work flexibly and creatively;
      the therapeutic work also extended to the wider context of the inpatient unit, in
      efforts to promote a shared understanding of service users' difficulties.
      CONCLUSIONS: Therapeutic relationships between service users and clinicians need
      to be promoted more broadly within acute inpatient care. Psychological
      formulation can help both service users and ward staff in understanding crisis
      and working collaboratively. Practice-based evidence is needed to demonstrate the
      effectiveness of adapted psychological therapy models. PRACTITIONER POINTS:
      Developing 'human' relationships at all levels of acute inpatient care continues
      to be an important challenge for clinical practice. Due to the distress of
      individuals and the constraints of the acute inpatient environment, psychologists
      need to be flexible and adaptable in delivering individual therapy. Making
      meaning and psychological formulation can give service users a sense of hope and
      empowerment, and can contribute to a shared understanding within the ward team of
      service users' difficulties.

PMID- 29345803
TI  - Effects of mindfulness-based cognitive therapy on shame, self-compassion and
      psychological distress in anxious and depressed patients: A pilot study.
AB  - OBJECTIVES: The tendency to experience shame or guilt is associated
      differentially with anxiety and depression, with shame being associated with
      greater psychopathology. Correlational studies have shown self-compassion to be
      related to lower shame and rumination, and mindfulness-based interventions
      increase self-compassion. Therefore, mindfulness-based interventions may decrease
      shame. This pilot study aimed to assess the association of shame, rumination,
      self-compassion, and psychological distress and the effects of a mindfulness
      based intervention on these measures in a clinical sample. DESIGN: Single-group
      design with pre-test and post-test measures. METHOD: Thirty-two service users who
      experienced clinically diagnosed depressive or anxiety disorders in a mindfulness
      based cognitive therapy programme were assessed before and twenty-two after
      therapy with measures of shame-proneness, external shame, rumination, self
      compassion, and psychological distress. RESULTS: Shame-proneness and external
      shame were positively correlated with self-coldness, and external shame was
      positively correlated with stress and depressive symptoms. Self-compassion
      increased and self-coldness decreased, while shame-proneness, rumination,
      anxiety, and stress symptoms decreased from pre- to post-treatment. There was no
      significant reduction in depressive symptoms, guilt-proneness, or external shame.
      CONCLUSION: Our preliminary findings suggest that mindfulness-based approaches
      may be helpful in increasing self-compassion and reducing shame-proneness in
      mixed groups of anxious and depressed patients. Controlled studies of the effects
      of mindfulness-based interventions on shame in clinical populations are
      warranted. PRACTITIONER POINTS: Shame-proneness and external shame showed
      different patterns of relationship with depressive and stress symptoms and with
      self-compassion. Shame-proneness decreased to a greater extent than external
      shame decreased following participation in an MBCT group. Mindfulness-based
      interventions may benefit shame-proneness to a greater extent than external
      shame.

PMID- 29345804
TI  - MoP Nanoparticles Supported on Indium-Doped Porous Carbon: Outstanding Catalysts
      for Highly Efficient CO2 Electroreduction.
AB  - Electrochemical reduction of CO2 into value-added product is an interesting area.
      MoP nanoparticles supported on porous carbon were synthesized using metal-organic
      frameworks as the carbon precursor, and initial work on CO2 electroreduction
      using the MoP-based catalyst were carried out. It was discovered that MoP
      nanoparticles supported on In-doped porous carbon had outstanding performance for
      CO2 reduction to formic acid. The Faradaic efficiency and current density could
      reach 96.5 % and 43.8 mA cm-2 , respectively, when using ionic liquid 1-butyl-3
      methylimidazolium hexafluorophosphate as the supporting electrolyte. The current
      density is higher than those reported up to date with very high Faradaic
      efficiency. The MoP nanoparticles and the doped In2 O3 cooperated very well in
      catalyzing the CO2 electroreduction.

PMID- 29345805
TI  - Is the widely used two-factor structure of the Ruminative Responses Scale
      invariant across different samples of women?
AB  - OBJECTIVES: Although the Ruminative Responses Scale is one of the most widely
      used measures of rumination, its two-factor structure remains controversial.
      Taking this into account, we aimed to test the RRS-10 two-factor invariance
      (Brazilian version) between different samples of women and to study its internal
      consistency and convergent validity. METHODS: A sample of 321 women (general
      population, n = 106; college students, n = 115; and medical population of
      patients with overweight and obesity, n = 100) participated in the study. The two
      factor structure of RRS-10 was assessed by CFA and multigroup analysis using
      Mplus software. Internal consistency was assessed by Cronbach's alpha and the
      convergent validity by Pearson correlations. RESULTS: The two-factor structure of
      RRS-10 showed a good fit, factorial invariance across three samples, good
      internal consistency, and adequate convergent validity. Brooding and Reflection
      subscales were both positively correlated with psychological inflexibility,
      cognitive fusion, anxiety, depression, and stress symptoms, although Brooding
      presented significantly stronger associations with these variables than
      Reflection. CONCLUSIONS: This study provides further discussion and evidence
      regarding the RRS-10 two-factor structure, as well as a valid version of RRS-10
      to use in Brazil in order to reliably assess rumination in medical and research
      settings. PRACTITIONER POINTS: This is the first study to test and confirm the
      RRS two-factor structure invariance across groups. RRS-10 two-dimensionality was
      confirmed in medical and non-medical samples of women. Brooding subscale showed
      significantly stronger relationships with psychopathology and experiential
      avoidance than Reflection. The study provides evidence that RRS can be used as a
      valid and sound measure to accurately assess the clinically relevant dimensions
      of rumination simultaneously across distinct groups.

PMID- 29345806
TI  - Response to Dr. Finucane.

PMID- 29345807
TI  - Targeting a Dark Excited State of HIV-1 Nucleocapsid by Antiretroviral Thioesters
      Revealed by NMR Spectroscopy.
AB  - HIV-1 nucleocapsid (NCp7) is a two Cys2 HisCys zinc knuckle (N-Zn and C-Zn)
      protein that plays a key role in viral replication. NCp7 conformational dynamics
      is characterized by NMR relaxation dispersion and chemical exchange saturation
      transfer measurements. While the N-Zn knuckle is conformationally stable, the C
      Zn knuckle interconverts on the millisecond timescale between the major state, in
      which the zinc is coordinated by three cysteines and a histidine, and two folded
      minor species (with populations around 1 %) in which one of the coordination
      bonds (Cys413-Sgamma-Zn or His421-Nepsilon2-Zn) is hydrolyzed. These findings
      explain why antiretroviral thioesters specifically disrupt the C-Zn knuckle by
      initial acylation of Cys413, and show that transient, sparsely-populated
      ("dark"), excited states of proteins can present effective targets for rational
      drug design.

PMID- 29345808
TI  - Immune protective effects of chitooligosaccharides on mice genital tract infected
      by Chlamydia trachomatis.
AB  - PROBLEM: The immune protective effects of chitooligosaccharides (COs) on mouse
      genital tract infected by Chlamydia trachomatis (Ct) were unknown. METHODS: The
      minimum effective/infective dose was obtained by establishing the murine model of
      the genital tract infected by Ct. The model mice were treated with different
      doses (0.1, 0.2, and 0.3 g/kg,) of COs and 0.9% saline, and the serum
      immunoglobulin G (IgG) antibody and interleukin (IL)-11 levels were then assayed.
      The healthy mice were used as the control. After 1 week of immunity, a double
      effective/infective dose of Ct was used to attack the genital tract. After 10
      days of experiment, the mice were killed, their spleen and thymus indexes were
      determined, and the pathological changes in their genital tract were evaluated.
      RESULTS: Treatment with COs increased the serum IgG antibody, IL-11 levels, and
      spleen and thymus indexes but decreased the positive infection rate and inclusion
      body formation with Ct. CONCLUSION: COs could induce immune protection on the Ct
      infected mouse genital tract and might be used as an alternative drug for the
      treatment of genital tract infected with Ct.

PMID- 29345809
TI  - Peroxisomes in lipid metabolism.
AB  - Gene targeting and the elucidation of mutations underlying inherited peroxisomal
      diseases have provided new insights in peroxisomal lipid metabolism in vivo. The
      work led to the identification of a novel peroxisomal beta-oxidation pathway and
      established clearly that genes, which are required for efficient peroxisomal
      oxidation of fatty acids, at the same time are key regulators of PPARalpha
      function in vivo. The new mouse models may provide helpful tools in the search
      for unknown natural PPARalpha agonists and in screening for in vivo PPARalpha
      antagonists. J. Cell Biochem. Suppls. 30/31:158-167, 1998. (c) 1998 Wiley-Liss,
      Inc.

PMID- 29345810
TI  - Communication between the cell membrane and the nucleus: Role of protein
      compartmentalization.
AB  - Understanding how the information is conveyed from outside to inside the cell is
      a critical challenge for all biologists involved in signal transduction. The flow
      of information initiated by cell-cell and cell-extracellular matrix contacts is
      mediated by the formation of adhesion complexes involving multiple proteins.
      Inside adhesion complexes, connective membrane skeleton (CMS) proteins are signal
      transducers that bind to adhesion molecules, organize the cytoskeleton, and
      initiate biochemical cascades. Adhesion complex-mediated signal transduction
      ultimately directs the formation of supramolecular structures in the cell
      nucleus, as illustrated by the establishment of multi complexes of DNA-bound
      transcription factors, and the redistribution of nuclear structural proteins to
      form nuclear subdomains. Recently, several CMS proteins have been observed to
      travel to the cell nucleus, suggesting a distinctive role for these proteins in
      signal transduction. This review focuses on the nuclear translocation of
      structural signal transducers of the membrane skeleton and also extends our
      analysis to possible translocation of resident nuclear proteins to the membrane
      skeleton. This leads us to envision the communication between spatially distant
      cellular compartments (i.e., membrane skeleton and cell nucleus) as a
      bidirectional flow of information (a dynamic reciprocity) based on subtle
      multilevel structural and biochemical equilibria. At one level, it is mediated by
      the interaction between structural signal transducers and their binding partners,
      at another level it may be mediated by the balance and integration of signal
      transducers in different cellular compartments. J. Cell. Biochem. Suppls.
      30/31:250-263, 1998. (c) 1998 Wiley-Liss, Inc.

PMID- 29345811
TI  - Osteopontin expression and function: Role in bone remodeling.
AB  - The cytokine and cell attachment protein osteopontin (OPN) is not necessary for
      the development and survival of mice in a clean animal facility. The primary role
      of OPN appears to be that of facilitating recovery of the organism after injury
      or infection, which generally causes an increase in its expression. It also is
      essential for some forms of bone remodeling. OPN stimulates cellular signaling
      pathways via various receptors found on most cell types and can encourage cell
      migration. OPN modulates immune and inflammatory responses and possibly
      negatively regulates Ras signaling pathways. Its apparent ability to enhance cell
      survival by inhibiting apoptosis may explain why the metastatic proficiency of
      tumor cells increases with increased OPN expression. J. Cell. Biochem. Suppls.
      30/31:92-102, 1998. (c) 1998 Wiley-Liss, Inc.

PMID- 29345812
TI  - Role of histone deacetylases in acute leukemia.
AB  - Accumulating evidence points to a connection between cancer and transcriptional
      control by histone acetylation and deacetylation. This is particularly true with
      regard to the acute leukemias, many of which are caused by fusion proteins that
      have been created by chromosomal translocations. Genetic rearrangements that
      disrupt the retinoic acid receptor-alpha and acute myeloid leukemia-1 genes
      create fusion proteins that block terminal differentiation of hematopoietic cells
      by repressing transcription. These fusion proteins interact with nuclear hormone
      co-repressors, which recruit histone deacetylases to promoters to repress
      transcription. This finding suggests that proteins within the histone deacetylase
      complexes may be potential targets for pharmaceutical intervention in many
      leukemia patients. J. Cell. Biochem. Suppls. 30/31:194-202, 1998. (c) 1998 Wiley
      Liss, Inc.

PMID- 29345813
TI  - High throughput analysis of differential gene expression.
AB  - Elucidation of the changes in gene expression associated with biological
      processes is a central problem in biology. Advances in molecular and
      computational biology have led to the development of powerful, high-thoughput
      methods for the analysis of differential gene expression. These tools have opened
      up new opportunities in disciplines ranging from cell and developmental biology
      to drug development and pharmacogenomics. In this review, the attributes of five
      commonly used differential gene expression methods are discussed: expressed
      sequence tag (EST) sequencing, cDNA microarray hybridization, subtractive
      cloning, differential display, and serial analysis of gene expression (SAGE). The
      application of EST sequencing and microarray hybridization is illustrated by the
      discovery of novel genes associated with osteoblast differentiation. The
      application of subtractive cloning is presented as a tool to identify genes
      regulated in vivo by the transcription factor pax-6. These and other examples
      illustrate the power of genomics for discovering novel genes that are important
      in biology and which also represent new targets for drug development. The central
      theme of the review is that each of the approaches to identifying differentially
      expressed genes is useful, and that the experimental context and subsequent
      evaluation of differentially expressed genes are the critical features that
      determine success. J. Cell. Biochem. Suppls. 30/31:286-296, 1998. (c) 1998 Wiley
      Liss, Inc.

PMID- 29345814
TI  - Promiscuous subunit interactions: A possible mechanism for the regulation of
      protein kinase CK2.
AB  - Protein kinase CK2 is a ubiquitous eukaryotic ser/thr protein kinase. The active
      holoenzyme is a heterotetrameric protein composed of catalytic (alpha and alpha')
      and regulatory (beta) subunits that phosphorylates many different protein
      substrates and appears to be involved in the regulation of cell division. Despite
      important structural studies, the intimate details of the interactions of the
      alpha catalytic subunits with the beta regulatory subunits are unknown. Recent
      evidence that indicates that both CK2 subunits can interact promiscuously with
      other proteins in a manner that excludes the binding of their complementary CK2
      partners has opened the possibility that the phosphorylating activity of this
      enzyme may be regulated in a novel way. These alternative interactions could
      limit the in vivo availability of CK2 subunits to generate fully active
      holoenzyme CK2 tetramers. Likewise, variations in the ratio of alpha- and beta
      subunits could determine the activity of several phosphorylating and
      dephosphorylating activities. The promiscuity of the CK2 subunits can be
      extrapolated to a more widespread phenomenon in which "wild-card" proteins could
      act as general switches by interacting and regulating several catalytic
      activities. J. Cell. Biochem. Suppls. 30/31:129-136, 1998. (c) 1998 Wiley-Liss,
      Inc.

PMID- 29345815
TI  - In search of cellular control: Signal transduction in context.
AB  - The field of molecular cell biology has experienced enormous advances over the
      last century by reducing the complexity of living cells into simpler molecular
      components and binding interactions that are amenable to rigorous biochemical
      analysis. However, as our tools become more powerful, there is a tendency to
      define mechanisms by what we can measure. The field is currently dominated by
      efforts to identify the key molecules and sequences that mediate the function of
      critical receptors, signal transducers, and molecular switches. Unfortunately,
      these conventional experimental approaches ignore the importance of
      supramolecular control mechanisms that play a critical role in cellular
      regulation. Thus, the significance of individual molecular constituents cannot be
      fully understood when studied in isolation because their function may vary
      depending on their context within the structural complexity of the living cell.
      These higher-order regulatory mechanisms are based on the cell's use of a form of
      solid-state biochemistry in which molecular components that mediate biochemical
      processing and signal transduction are immobilized on insoluble cytoskeletal
      scaffolds in the cytoplasm and nucleus. Key to the understanding of this form of
      cellular regulation is the realization that chemistry is structure and hence,
      recognition of the importance of architecture and mechanics for signal
      integration and biochemical control. Recent work that has unified chemical and
      mechanical signaling pathways provides a glimpse of how this form of higher-order
      cellular control may function and where paths may lie in the future. J. Cell.
      Biochem. Suppls. 30/31:232-237, 1998. (c) 1998 Wiley-Liss, Inc.

PMID- 29345816
TI  - Initiation of DNA replication in eukaryotic chromosomes.
AB  - Our understanding of the process by which eukaryotes regulate initiation of DNA
      replication has made remarkable advances in the past few years, thanks in large
      part to the explosion of genetic and biochemical information on the budding
      yeast, Saccharomyces cerevisiae. At least three major concepts have emerged: 1)
      The sequence of molecular events that determines when replication begins and how
      frequently each replication site is used are conserved among most, if not all,
      eukaryotes; 2) specific replication origins are used in most, if not all,
      eukaryotes that consist of a flexible modular anatomy; and 3) epigenetic factors
      such as chromatin structure and nuclear organization determine which of many
      potential replication origins are used at different stages in animal development.
      Thus, the current state of our knowledge suggests a simple unifying concept-all
      eukaryotes utilize the same basic proteins and DNA sequences to initiate
      replication, but the metazoa can change both the number and locations of
      replication origins in response to the demands of animal development. J. Cell.
      Biochem. Suppls. 30/31:8-17, 1998.

PMID- 29345817
TI  - Intranuclear targeting of DNA replication factors.
AB  - Mammalian nuclei are highly organized into functional compartments. Major nuclear
      processes like DNA replication and RNA processing take place in distinct foci.
      These microscopically visible foci are formed by the assembly of, for example,
      DNA replication factors and associated proteins into megadalton complexes often
      referred to as protein machines or factories. Thus far, two proteins, DNA ligase
      I and DNA methyltransferase (DNA MTase), have been analyzed in greater detail. In
      both cases, the assembly process appears to be controlled by distinct targeting
      sequences that were attached to the catalytic protein core in the course of
      evolution and mediate the association with replication factories in mammalian
      cells. The dynamics of these nuclear structures throughout the cell cycle are
      analyzed using green fluorescent protein (GFP). Further studies are needed to
      elucidate the architecture, regulation, and role of these subnuclear structures.
      J. Cell. Biochem. Suppls. 30/31:243-249, 1998. (c) 1998 Wiley-Liss, Inc.

PMID- 29345818
TI  - Biomineralization: Conflicts, challenges, and opportunities.
AB  - Biomineralization is the process by which mineral crystals are deposited in an
      organized fashion in the matrix (either cellular or extracellular) of living
      organisms. Over the past 25 years, new insights into the mechanisms that control
      these processes have been obtained, yet questions asked then still persist,
      especially in terms of vertebrate mineralization. Specifically, there are still
      debates concerning the chemical nature of the first mineral crystals formed in
      bone, dentin, and cementum; the factors leading to the initial deposition of
      these crystals; and the functions of macromolecules found associated with these
      crystals. In this review, emphasis is placed on the currently accepted answers to
      these questions, drawing insight from nonvertebrate systems. It is suggested that
      there are redundant calcification mechanisms and that, by taking advantage of our
      current knowledge of these mechanisms, opportunities will be provided for
      therapeutic manipulation of diseases in which biomineralization is impaired. J.
      Cell. Biochem. Suppls. 30/31:83-91, 1998. (c) 1998 Wiley-Liss, Inc.

PMID- 29345819
TI  - Steroid receptors at the nexus of transcriptional regulation.
AB  - During the past few years, our understanding of nuclear receptor action has
      dramatically improved as a result of the identification and functional analysis
      of co-regulators such as factors involved in chromatin remodeling, transcription
      intermediary factors (co-repressors and co-activators), and direct interactions
      with the basal transcriptional machinery. Furthermore, the elucidation of the
      crystal structures of the empty ligand-binding domains of the nuclear receptor
      and of complexes formed by the nuclear receptor's ligand-binding domain bound to
      agonists and antagonists has contributed significantly to our understanding of
      the early events of nuclear receptor action. However, the picture of hormone- and
      hormone receptor-mediated mechanisms of gene regulation remain incomplete and
      extremely complicated when one also considers the "nontraditional" interactions
      of hormone-activated nuclear receptors, for example, interactions between the
      activated steroid receptors and components of the chromatin/nuclear matrix; and
      finally the nongenomic effects that steroid hormones can exhibit with other
      signaling pathways. In this prospectus on steroid receptors, we discuss the
      implications of various steroid hormone and nuclear receptor interactions and
      potential future directions of investigation. J. Cell. Biochem. Suppls. 30/31:185
      193, 1998. (c) 1999 Wiley-Liss, Inc.

PMID- 29345820
TI  - Marrow stromal cells as stem cells for continual renewal of nonhematopoietic
      tissues and as potential vectors for gene therapy.

PMID- 29345821
TI  - Oligosaccharide signaling of plant cells.
AB  - A variety of oligosaccharide signals have been identified that function in the
      regulation of plant development, defense, and other interactions of plants with
      the environment. Some of these oligosaccharides are produced by various pathogens
      or symbionts, whereas others are synthesized by the plant itself. This mini
      review summarizes our present state of information on these oligosaccharide
      signals and provides an overview of approaches being used to identify receptors
      for these signals and gain an understanding of the mechanism(s) by which these
      signals activate downstream events. Possible biotechnological applications of
      future work in this field are also considered. J. Cell. Biochem. Suppls.
      30/31:123-128, 1998. (c) 1998 Wiley-Liss, Inc.

PMID- 29345823
TI  - Color section.

PMID- 29345822
TI  - Linkages of nuclear architecture to biological and pathological control of gene
      expression.
AB  - Functional interrelationships between components of nuclear architecture and
      control of gene expression are becoming increasingly evident. There is growing
      appreciation that multiple levels of nuclear organization integrate the
      regulatory cues that support activation and suppression of genes as well as the
      processing of gene transcripts. The linear organization of genes and promoter
      elements provide the potential for responsiveness to physiological regulatory
      signals. Parameters of chromatin structure and nucleosome organization support
      synergism between activities at independent regulatory sequences and render
      promoter elements accessible or refractory to transcription factors. Association
      of genes, transcription factors, and the machinery for transcript processing with
      the nuclear matrix facilitates fidelity of gene expression within the three
      dimensional context of nuclear architecture. Mechanisms must be defined that
      couple nuclear morphology with enzymatic parameters of gene expression. The
      recent characterization of factors that mediate chromatin remodeling and
      intranuclear targeting signals that direct transcription factors to subnuclear
      domains where gene expression occurs, reflect linkage of genetic and structural
      components of transcriptional control. Nuclear reorganization and aberrant
      intranuclear trafficking of transcription factors for developmental and tissue
      specific control that occurs in tumor cells and in neurological disorders
      provides a basis for high resolution diagnostics and targeted therapy. J. Cell.
      Biochem. Suppls. 30/31:220-231, 1998. (c) 1998 Wiley-Liss, Inc.

PMID- 29345824
TI  - The S phase: Beginning, middle, and end: A perspective.
AB  - Events in the S phase of the cell cycle have been investigated to a relatively
      limited extent in comparison with those in G1 and M phases. Four aspects of S are
      briefly discussed in this report: (1) the final biochemical step permitting
      initiation of DNA synthesis, (2) determination of replication timing of
      individual genes and its mechanism, (3) S phase processes that lead to the onset
      of M phase, and (4) resetting the S-phase machinery. J. Cell. Biochem. Suppls.
      30/31:1-7, 1998. (c) 1999 Wiley-Liss, Inc.

PMID- 29345825
TI  - Bone stem cells.
AB  - Osteoblasts are the skeletal cells responsible for synthesis, deposition, and
      mineralization of the extracellular matrix of bone. By mechanisms that are only
      beginning to be understood, stem and primitive osteoprogenitors and related
      mesenchymal precursors arise in the embryo and at least some appear to persist in
      the adult organism, where they contribute to replacement of osteoblasts in bone
      turnover and in fracture healing. In this paper, the nature of these cells,
      whether they constitute a stem cell pool or a committed progenitor pool, and
      aspects of their apparent plasticity are discussed. Current understanding of
      differential expression of osteoblast-associated genes during osteoprogenitor
      proliferation and differentiation to mature matrix synthesizing osteoblasts is
      summarized. Finally, evidence is discussed that supports the hypothesis that the
      mature osteoblast phenotype is heterogeneous with subpopulations of osteoblasts
      expressing only subsets of the known osteoblast markers, raising also the
      possibility of multiple parallel differentiation pathways and perhaps even
      different progenitor pools. J. Cell. Biochem. Suppls. 30/31:73-82, 1998. (c) 1998
      Wiley-Liss, Inc.

PMID- 29345826
TI  - Nucleosome and chromatin structures and functions.

PMID- 29345827
TI  - The ongoing saga of osteoporosis treatment.

PMID- 29345828
TI  - Signal transduction by transforming growth factor-beta: A cooperative paradigm
      with extensive negative regulation.
AB  - Transforming growth factor-beta (TGF-beta) represents an evolutionarily conserved
      family of secreted factors that mobilize a complex signaling network to control
      cell fate by regulating proliferation, differentiation, motility, adhesion, and
      apoptosis. TGF-beta promotes the assembly of a cell surface receptor complex
      composed of type I (TbetaRI) and type II (TbetaRII) receptor serine/threonine
      kinases. In response to TGF-beta binding, TbetaRII recruits and activates TbetaRI
      through phosphorylation of the regulatory GS-domain. Activated TbetaRI then
      initiates cytoplasmic signaling pathways to produce cellular responses. SMAD
      proteins together constitute a unique signaling pathway with key roles in signal
      transduction by TGF-beta and related factors. Pathway-restricted SMADs are
      phosphorylated and activated by type I receptors in response to stimulation by
      ligand. Once activated, pathway-restricted SMADs oligomerize with the common
      mediator Smad4 and subsequently translocate to the nucleus. Genetic analysis in
      Drosophila melanogaster and Caenorhabditis elegans, as well as TbetaRII and SMAD
      mutations in human tumors, emphasizes their importance in TGF-beta signaling.
      Mounting evidence indicates that SMADs cooperate with ubiquitous cytoplasmic
      signaling cascades and nuclear factors to produce the full spectrum of TGF-beta
      responses. Operating independently, these ubiquitous elements may influence the
      nature of cellular responses to TGF-beta. Additionally, a variety of regulatory
      schemes contribute temporal and/or spatial restriction to TGF-beta responses.
      This report reviews our current understanding of TGF-beta signal transduction and
      considers the importance of a cooperative signaling paradigm to TGF-beta-mediated
      biological responses. J. Cell. Biochem. Suppls. 30/31:111-122, 1998. (c) 1998
      Wiley-Liss, Inc.

PMID- 29345829
TI  - Macromolecular exchanges between the nucleus and cytoplasm.
AB  - The control of transcription and translation is of fundamental importance in cell
      biology. In this regard, the nuclear envelope is in a unique position to
      contribute to the regulation of these events, by directing macromolecular
      exchanges between the nucleus and cytoplasm. Such exchanges occur through the
      nuclear pore complexes, mainly by signal-mediated processes. Different signals
      are required for import and export. Specific cytoplasmic or nuclear receptors
      initially bind the signal-containing substrate, and the complex subsequently
      interacts with the pores. Additional factors then assist in translocation across
      the envelope. Current research is focused mainly on further characterization of
      transport receptors, translocation factors, as well as components of the nuclear
      pore complex, i.e., the nucleoporins. The ultimate goal is to understand the
      molecular interactions that occur among the different components of the transport
      apparatus, the energy sources for transport, and how variations in transport
      capacity are generated. J. Cell. Biochem. Suppls. 30/31:214-219, 1998. (c) 1998
      Wiley-Liss, Inc.

PMID- 29345830
TI  - DNA vaccines: Vector design, delivery, and antigen presentation.
AB  - Inoculations with antigen-expressing plasmid DNAs (DNA vaccines) in the
      production of protective immune responses. Since the initial development of DNA
      vaccines more than 5 years ago, major strides have been made in the design of
      efficient vaccine vectors and in the process of vaccine delivery. However, many
      questions remain regarding the mechanism of cellular transfection and in the
      development of immune responses. This review addresses functional aspects of DNA
      vaccines, including vector design and delivery, as well as cellular transfection
      and antigen presentation. J. Cell. Biochem. Suppls. 30/31:304-311, 1998. (c) 1998
      Wiley-Liss, Inc.

PMID- 29345831
TI  - Signaling mechanisms and molecular characteristics of G protein-coupled receptors
      for lysophosphatidic acid and sphingosine 1-phosphate.
AB  - Lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) are potent
      phospholipid mediators with diverse biological activities. Their appearance and
      functional properties suggest possible roles in development, wound healing, and
      tissue regeneration. The growth-stimulating and other complex biological
      activities of LPA and S1P are attributable in part to the activation of multiple
      G protein-mediated intracellular signaling pathways. Several heterotrimeric G
      proteins, as well as Ras- and Rho-dependent pathways play central roles in the
      cellular responses to LPA and S1P. Recently, several G protein-coupled receptors
      encoded by a family of endothelial differentiation genes (edg) have been shown to
      bind LPA or S1P and transduce responses of cAMP, Ca2+ , MAP kinases, Rho, and
      gene transcription. This review summarizes our current understanding of signaling
      pathways critical for cellular responses to LPA and S1P and of recent progress in
      the molecular biological analyses of the Edg receptors. J. Cell. Biochem. Suppls.
      30/31:147-157, 1998. (c) 1998 Wiley-Liss, Inc.

PMID- 29345832
TI  - Introduction.

PMID- 29345833
TI  - Osteocalcin gene promoter: Unlocking the secrets for regulation of osteoblast
      growth and differentiation.
AB  - The bone tissue-specific osteocalcin gene remains one of a few genes that
      exhibits osteoblast-restricted expression. Over the last decade, characterization
      of the promoter regulatory elements and complexes of factors that control
      suppression of the osteocalcin gene in osteoprogenitor cells and transactivation
      in mature osteoblasts has revealed transcriptional regulatory mechanisms that
      mediate development of the osteoblast phenotype. In this review, we have focused
      on emerging concepts related to molecular mechanisms supporting osteoblast growth
      and differentiation based on the discoveries that the osteocalcin gene is
      regulated by homeodomain factors, AP-1 related proteins, and the bone restricted
      Cbfa1/AML3 transcription factor. J. Cell. Biochem. Suppls. 30/31:62-72, 1998. (c)
      1998 Wiley-Liss, Inc.

PMID- 29345834
TI  - A role for cadherins in cellular signaling and differentiation.
AB  - Cadherins form a family of cell-cell adhesion proteins that are critical to
      normal embryonic development. Expression of the various family members is
      regulated in a complex pattern during embryogenesis. Both reduced and
      inappropriate expression of cadherins have been associated with abnormal tissue
      formation in embryos and tumorigenesis in mature organisms. Evidence is
      accumulating that signals unique to individual members of the cadherin family, as
      well as signals common to multiple cadherins, contribute to the differentiated
      phenotype of various cell types. While a complete understanding of the regulation
      of cadherin expression of the molecular nature of intracellular signaling
      downstream of cadherin adhesion is essential to an understanding of embryogenesis
      and tumorigenesis, our knowledge in both areas is inadequate. Clearly,
      elucidating the factors and conditions that regulate cadherin expression and
      defining the signaling pathways activated by cadherins are frontiers for future
      research. J. Cell. Biochem. Suppls. 30/31:168-176, 1998. (c) 1998 Wiley-Liss,
      Inc.

PMID- 29345835
TI  - Translocations, fusion genes, and acute leukemia.
AB  - Genes involved in chromosomal translocations, associated with the formation of
      fusion proteins in leukemia, are modular in nature and regulatory in function. It
      is likely that they are involved in the initiation and maintenance of normal
      hematopoiesis. A conceptual model is proposed by which disruption of these
      different genes leads to the development of acute leukemia. Central to this model
      is the functional interaction between the mammalian trithorax and polycomb group
      protein complexes. Many of the genes identified in leukemia-associated
      translocations are likely upstream regulators, co-participators or downstream
      targets of these complexes. In the natural state, these proteins interact with
      each other to form multimeric higher-order structures, which sequentially
      regulate the development of the normal hematopoietic state, either through HOX
      gene expression or other less defined pathways. The novel interaction domains
      acquired by the chimaeric fusion products subvert normal cellular control
      mechanisms, which result in both a failure of cell maturation and activation of
      anti-apoptotic pathways. The mechanisms by which these translocation products are
      able to affect these processes are thought to lie at the level of chromatin
      mediated transcriptional activation and/or repression. The stimuli for
      proliferation and development of clinically overt disease may require subsequent
      mutations in more than one oncogene or tumor suppressor gene, or both. A more
      comprehensive catalogue of mutation events in malignant cells is therefore
      required to understand the key regulatory networks that serve to maintain
      multipotentiality and in particular the modifications which initiate and
      coordinate commitment in differentiating hematopoietic cells. We propose a model
      in which common pathways for leukemogenesis lie along the cell cycle control of
      chromatin structure in terms of transcriptional activation or repression. A
      clearer understanding of this cascade will provide opportunities for the design
      and construction of novel biological agents that are able to restore normal
      regulatory mechanisms. J. Cell. Biochem. Suppls. 30/31:264-276, 1998. (c) 1998
      Wiley-Liss, Inc.

PMID- 29345836
TI  - Regulation of intracellular membrane interactions: Recent progress in the field
      of neurotransmitter release.
AB  - Maintenance of compartmental independence and diversity is part of the blueprint
      of the eukaryotic cell. The molecular composition of every organelle membrane is
      custom tailored to fulfill its unique tasks. It is retained by strict sorting and
      directional transport of newly synthesized cellular components by the use of
      specific transport vesicles. Temporally and spatially controlled membrane fission
      and fusion steps thus represent the basic process for delivery of both, membrane
      bound and soluble components to their appropriate destination. This process is
      fundamental to cell growth, organelle inheritance during cell division, uptake
      and intracellular transport of membrane-bound and soluble molecules, and neuronal
      communication. The latter process has become one of the best studied examples in
      terms of regulatory mechanisms of membrane interactions. It has been dissected
      into the stages of transmitter vesicle docking, priming, and fusion: Specificity
      of membrane interactions depends on interactions between sets of organelle
      specific membrane proteins. Priming of the secretory apparatus is an ATP
      dependent process involving proteins and membrane phospholipids. Release of
      vesicle content is triggered by a rise in intracellular free Ca2+ levels that
      relieves a block previously established between the membranes poised to fuse.
      Neurotransmitter release is a paradigm of highly regulated intracellular membrane
      interaction and molecular mechanisms for this phenomenon begin to be delineated.
      J. Cell. Biochem. Suppls. 30/31:103-110, 1998. (c) 1998 Wiley-Liss, Inc.

PMID- 29345837
TI  - Regulation and regulatory parameters of histone modifications.
AB  - Histone acetylation and phosphorylation destablizes nucleosome and chromatin
      structure. Relaxation of the chromatin fiber facilitates transcription.
      Coactivator complexes with histone acetyltransferase activity are recruited by
      transcription factors bound to enhancers or promoters. The recruited histone
      acetyltransferases may acetylate histone or nonhistone chromosomal proteins,
      resulting in the relaxation of chromatin structure. Alternatively, repressors
      recruit corepressor complexes with histone deacetylase activity, leading to
      condensation of chromatin.This review highlights the recent advances made in our
      understanding of the roles of histone acetyltransferases, histone deacetylases,
      histone kinases, and protein phosphatases in transcriptional activation and
      repression. Exciting reports revealing mechanistic connections between histone
      modifying activities and the RNA polymerase II machinery, the coupling of histone
      deacetylation and DNA methylation, the possible involvement of histone
      deacetylases in the organization of nuclear DNA, and the role of chromatin
      modulators in oncogenesis are discussed. J. Cell. Biochem. Suppls. 30/31:203-213,
      1998. (c) 1998 Wiley-Liss, Inc.

PMID- 29345838
TI  - Tissue engineering: The first decade and beyond.
AB  - This article reviews the important developments in the field of tissue
      engineering over the last 10 years. Research in the area of biomaterials is
      examined from the perspective of providing the foundation for the development of
      tissue engineering. Early efforts combining cells with biocompatible materials
      are described and applications of this technology presented, with particular
      focus on uses in orthopaedics and maxillofacial surgery. The basic principles of
      tissue engineering and state-of-the-art technology in cell biology and materials
      science as used currently in the field are presented. Finally, futures challenges
      are outlined from the perspective of integrating technologies from medicine,
      biology, and engineering, in hopes of translating tissue engineering to clinical
      applications. J. Cell. Biochem. Suppls. 30/31:297-303, 1998. (c) 1998 Wiley-Liss,
      Inc.

PMID- 29345839
TI  - G-protein regulatory pathways: Rocketing into the twenty-first century.
AB  - Complex cellular responses involve the integration of heterotrimeric G protein
      systems with protein kinase signal transduction pathways. Key in this integration
      is the control of small GTP-binding proteins including Ras and Rho family
      members. In this paper, we discuss the control of signal transduction pathways by
      G proteins and their integration with specific tyrosine kinases. The integration
      of G proteins, kinases, and small GTP-binding proteins in controlling cellular
      responses is illustrated through the newly defined Galpha12/13 -regulated
      pathways. Furthermore, the polymorphonuclear leukocyte provides a primary cell
      system for analyzing the integration of G proteins, kinases, and small GTP
      binding proteins in controlling cellular functions such as superoxide production,
      adherence, chemotaxis, and granule secretion. J. Cell. Biochem. Suppls. 30/31:137
      146, 1998. (c) 1998 Wiley-Liss, Inc.

PMID- 29345840
TI  - The new paradigm: Integrating genomic function and nuclear architecture.
AB  - A new view of the cell nucleus is emerging based on the functional dynamics of
      nuclear architecture. The striking structural preservation of a variety of
      genomic processes on the nuclear matrix provides an important approach for
      correlating nuclear form and function. In situ labeling coupled with three
      dimensional microscopy and computer imaging techniques shows that DNA replication
      and transcription sites are organized into higher-order units, or "zones," in the
      cell nucleus. The dynamic interplay and "re-zoning" of replication and
      transcription regions during the cell cycle may form the structural basis for the
      elaborate global coordination of replicational and transcriptional programs in
      the mammalian cell. J. Cell. Biochem. Suppls. 30/31:238-242, 1998. (c) 1998 Wiley
      Liss, Inc.

PMID- 29345841
TI  - Effects of high-impact exercise on the physical properties of bones of
      ovariectomized rats fed to a high-protein diet.
AB  - The aim of this study was to evaluate the effects of high-impact physical
      exercise as a prophylactic and therapeutic means in osteopenic bones of rats
      submitted to ovariectomy and protein diet intake. A total of 64 Wistar rats were
      divided into eight groups (n = 8 each), being: OVX, ovx, standard diet and
      sedentary; OVXE, ovx, standard diet and jump; OVXP, ovx, high-protein diet and
      sedentary; and OVXEP, ovx, high-protein diet and jump; SH, sham, standard diet
      and sedentary; SHE, sham, standard diet and jump; SHP, sham, high-protein diet
      and sedentary; and SHEP, sham, high-protein diet and jump. OVX surgery consists
      of ovariectomy, and sham was the control surgery. The jumping protocol consisted
      of 20 jumps/day, 5 days/week. The bone structure was evaluated by densitometry,
      mechanical tests, histomorphometric, and immunohistochemical analyses. A high
      protein diet resulted in increased bone mineral density (P = .049), but decreased
      maximal load (P = .026) and bone volume fraction (P = .023). The benefits of
      physical exercise were demonstrated by higher values of the maximal load in the
      trained groups compared to the sedentary groups (P < .001). The sham groups had
      decreased immunostaining of osteocalcin (P = .004) and osteopontin (P = .010)
      compared to ovx groups. However, the high-protein diet (P = .005) and jump
      exercise (P = .017) resulted in lower immunostaining of osteopontin compared to
      the standard diet and sedentary groups, respectively. In this experimental model,
      it was concluded that ovariectomy and a high-fat diet can negatively affect bone
      tissue and the high-impact exercise was not enough to suppress the deleterious
      effects caused by the protein diet and ovariectomy.

PMID- 29345843
TI  - Does the Use of Epiduroscopic Lysis of Adhesions Reduce the Need for Spinal Cord
      Stimulation in Failed Back Surgery Syndrome? A Short-Term Pilot Study.
AB  - BACKGROUND AND AIMS: Persistent low back pain after initially successful surgery
      that is not attributed to structural deficits is called failed back surgery
      syndrome (FBSS). When conservative and minimal invasive therapy fail, the
      recommended treatment is spinal cord stimulation (SCS). Because epidural fibrosis
      can be a contributing factor in the majority of FBSS patients, lumbosacral
      epiduroscopic lysis of adhesions may be considered as a less invasive alternative
      treatment option. We hypothesized that the use of epiduroscopic lysis of
      adhesions could reduce the need for SCS. METHODS: A pilot study was performed in
      35 consecutive patients with FBSS who underwent epiduroscopic lysis of adhesions.
      SCS was considered if epiduroscopic lysis of adhesions gave less than 50% global
      perceived effect (GPE) improvement after 15 months of follow-up. The GPE was
      measured 1 week and 6 months after the procedure. RESULTS: Over a period of 69
      months, 35 patients were included. After 15 months of follow-up, 43% of patients
      required SCS. Eight of the 15 patients who reported no short-term improvement
      needed SCS; those patients had severe epidural fibrosis. One week after
      epiduroscopic lysis of adhesions, 34%, 23%, and 43% of patients reported GPE
      improvement of > 50%, 20% to 50%, and < 20%, respectively. After 6 months, 5
      patients were lost to follow-up, and 30%, 17%, and 16% of patients reported
      improvement of > 50%, 20% to 50%, and < 20%, respectively. CONCLUSIONS: In this
      pilot study we observed a reduced need for SCS when lumbosacral epiduroscopic
      lysis of adhesions was used for patients with FBSS and magnetic resonance imaging
      proven adhesions. These observations justify the evaluation of both treatment
      options in a prospective observational trial.

PMID- 29345842
TI  - Programmed death-ligand 1 is a promising blood marker for predicting tumor
      progression and prognosis in patients with gastric cancer.
AB  - Immune checkpoint inhibitor therapy has been clinically introduced for several
      malignancies, and its effectiveness has been confirmed by clinical trials. In
      particular, programmed cell death protein 1 (PD-1) and programmed death-ligand 1
      (PD-L1) are widely known as important immune checkpoint molecules associated with
      the mechanisms of immune escape by malignant tumor cells. In addition, liquid
      biopsy of blood specimens has the clinical benefit of providing a simple,
      repeatable sampling tool. Non-invasive liquid biopsy has recently been
      spotlighted as a promising approach to predicting tumor progression and
      prognosis. This study assessed the clinical significance of PD-L1 mRNA expression
      in blood specimens obtained from patients with gastric cancer. Peripheral blood
      specimens were collected before treatment from 124 patients with gastric cancer.
      The PD-L1 mRNA expression was evaluated by quantitative RT-PCR. Programmed death
      ligand 1 mRNA expression was significantly higher in patients with advanced
      gastric cancer than in patients with early gastric cancer (P = .002). Moreover,
      PD-L1 expression correlated significantly with depth of tumor invasion, distant
      metastasis, and stage (P = .001, P < .001, and P < .001, respectively). Patients
      with high PD-L1 expression showed significantly poorer prognosis than those with
      low PD-L1 expression (P < .0001). Multivariate analysis indicated PD-L1
      expression as an independent prognostic factor. Expression of PD-L1 in peripheral
      blood may offer an immunological predictor of tumor progression and disease
      outcome in patients with gastric cancer.

PMID- 29345844
TI  - Assessing hepatitis C spontaneous clearance and understanding associated factors
      A systematic review and meta-analysis.
AB  - New advances in the treatment of hepatitis C provide high levels of sustained
      viral response but their expense limits availability in publicly funded health
      systems. The aim of this review was to estimate the proportion of patients who
      will spontaneously clear HCV, to identify factors that are associated with
      clearance and to support better targeting of directly acting antivirals. We
      searched Ovid EMBASE, Ovid MEDLINE and PubMed from 1 January 1994 to 30 June 2015
      for studies reporting hepatitis C spontaneous clearance and/or demographic,
      clinical and behavioural factors associated with clearance. We undertook meta
      analyses to estimate the odds of clearance for each predictor. Forty-three
      studies met the inclusion criteria, representing 20 110 individuals, and 6 of
      these studies included sufficient data to estimate spontaneous clearance. The
      proportion achieving clearance within 3, 6, 12 and 24 months following infection
      were, respectively, 19.8% (95% CI: 2.6%-47.5%), 27.9% (95% CI: 17.2%-41.8%),
      36.1% (95% CI: 23.5%-50.9%) and 37.1% (95% CI: 23.7%-52.8%). Individuals who had
      not spontaneously cleared by 12 months were unlikely to do so. The likelihood of
      spontaneous clearance was lower in males and individuals with HIV co-infection,
      the absence of HBV co-infection, asymptomatic infection, black or nonindigenous
      race, nongenotype 1 infection, older age and alcohol or drug problems. This study
      suggests that patients continue to spontaneously clear HCV for at least 12 months
      following initial infection. However, injecting drug users are comparatively less
      likely to achieve clearance; thus, they should be considered a priority for early
      treatment given the continuing risks that these individuals pose for onwards
      transmission.

PMID- 29345845
TI  - Atypical familial Mediterranean fever developed in a long-term hemodialysis
      patient.
AB  - Familial Mediterranean Fever (FMF) is usually an autosomal recessive
      autoinflammatory disease characterized by recurrent attacks of fever and
      serositis. FMF develops before the age of 20 years in 90% of patients. It has
      intervals of 1 week to several years between attacks, which leads to renal
      dysfunction-amyloidosis. We report a case of atypical FMF that developed in a
      long-term hemodialysis patient. A 65-year-old Japanese female undergoing
      hemodialysis for 32 years was referred to our hospital with a fever of unknown
      origin (FUO) following cervical laminoplasty. The fever occurred as recurrent
      attacks accompanied by oligoarthralgia of the left hip and knee. We suspected FMF
      because of recurrent self-limited febrile attacks, although the patient showed
      atypical clinical features such as late-onset and highly frequent attacks. After
      receiving treatment, she achieved a complete response to colchicine. Therefore, a
      diagnosis of FMF was made based on the Tel-Hashomer criteria, which was confirmed
      by genetic testing. The case suggests that FMF may be of note in long-term
      hemodialysis patients developing FUO.

PMID- 29345846
TI  - Stable and Highly Efficient Electrochemical Production of Formic Acid from Carbon
      Dioxide Using Diamond Electrodes.
AB  - High faradaic efficiencies can be achieved in the production of formic acid
      (HCOOH) by metal electrodes, such as Sn or Pb, in the electrochemical reduction
      of carbon dioxide (CO2 ). However, the stability and environmental load in using
      them are problematic. The electrochemical reduction of CO2 to HCOOH was
      investigated in a flow cell using boron-doped diamond (BDD) electrodes. BDD
      electrodes have superior electrochemical properties to metal electrodes, and,
      moreover, are highly durable. The faradaic efficiency for the production of HCOOH
      was as high as 94.7 %. Furthermore, the selectivity for the production of HCOOH
      was more than 99 %. The rate of the production was increased to 473 MUmol m-2  s
      1 at a current density of 15 mA cm-2 with a faradaic efficiency of 61 %. The
      faradaic efficiency and the production rate are almost the same as or larger than
      those achieved using Sn and Pb electrodes. Furthermore, the stability of the BDD
      electrodes was confirmed by 24 h operation.

PMID- 29345847
TI  - Characterizing the temporal evolution of the hepatitis C virus epidemic in
      Pakistan.
AB  - Pakistan has the second largest number of HCV infections in the world. We
      assessed past, present and future levels and trends of the HCV epidemic in
      Pakistan. An age-structured mathematical model was developed and analysed to
      describe transmission dynamics over 1980-2050. The model was fitted to a
      nationally representative survey and a comprehensive database of systematically
      gathered HCV Ab prevalence data. HCV Ab and chronic infection prevalences peaked
      at 5.3% and 3.9% in 2000 but were projected to decline to 4.3% and 3.2% by 2017,
      3.4% and 2.6% by 2030 and 2.6% and 1.9% by 2050, respectively. The number of
      chronically infected individuals was estimated at 6 663 906 in 2017 and was
      projected to peak at 6 665 900 in 2018 and decline to 6 372 100 in 2030 and 5 131
      500 in 2050. Annual number of new infections peaked at 346 740 in 1992 but was
      projected to decline to 198 320 in 2017, 151 090 in 2030 and 98 120 in 2050.
      Incidence rate per 100 000 person-year peaked at 343 in 1988 but was projected to
      decline to 99 in 2017, 62 in 2030 and 36 in 2050. Prevalence and incidence varied
      by age, and the majority of new infections occurred in the 20-39 age group.
      Prevalence and incidence of HCV in Pakistan have been slowly declining for two
      decades-Pakistan is enduring a large epidemic that will persist for decades if
      not controlled. Nearly, 10% of global infections are in Pakistan, with about 200
      000 additional infections every year. Rapid and mass scale-up of prevention and
      treatment programmes are critically needed.

PMID- 29345848
TI  - Economic evaluation of cognitive behavioral therapy and Internet-based guided
      self-help for binge-eating disorder.
AB  - OBJECTIVE: To determine the cost-effectiveness of individual face-to-face
      cognitive behavioral therapy (CBT) compared to therapist guided Internet-based
      self-help (GSH-I) in overweight or obese adults with binge-eating disorder (BED).
      METHOD: Analysis was conducted alongside the multicenter randomized controlled
      INTERBED trial. CBT (n = 76) consisted of up to 20 individual therapy sessions
      over 4 months. GSH-I (n = 71) consisted of 11 modules combining behavioral
      interventions, exercises including a self-monitoring food diary, psychoeducation,
      and 2 face-to-face coaching sessions over 4 months. Assessments at baseline,
      after 4 months (post-treatment), as well as 6 and 18 months after the end of
      treatment included health care utilization and sick leave days to calculate
      direct and indirect costs. Binge-free days (BFD) were calculated as effect
      measure based on the German version of the Eating Disorder Examination. The
      incremental cost-effectiveness ratio (ICER) was determined, and net benefit
      regressions, adjusted for comorbidities and baseline differences, were used to
      derive cost-effectiveness acceptability curves. RESULTS: After controlling for
      baseline differences, CBT was associated with non-significantly more costs
      (+?2,539) and BFDs (+40.1) compared with GSH-I during the 22-month observation
      period, resulting in an adjusted ICER of ?63 per additional BFD. CBTs probability
      of being cost-effective increased above 80% only if societal willingness to pay
      (WTP) was >=?250 per BFD. DISCUSSION: We did not find clear evidence for one of
      the treatments being more cost-effective. CBT tends to be more effective but also
      more costly. If the societal WTP for an additional BFD is low, then our results
      suggest that GSH-I should rather be adopted.

PMID- 29345849
TI  - Impact of cone beam computed tomography on periapical assessment and treatment
      planning five to eleven years after surgical endodontic retreatment.
AB  - AIM: To evaluate how additional information from Cone Beam CT (CBCT) impacts on
      periapical assessment and treatment planning based on clinical examination and
      periapical radiographs (PR) in cases followed up five to eleven years after
      surgical endodontic retreatment (SER). METHODOLOGY: Patients receiving SER during
      2004-2010 were reinvited for follow-up examination including clinical
      examination, PR, and CBCT. In total, 108 patients (119 teeth) were reinvited, 74
      patients (83 teeth) accepted to participate. Three observers initially assessed
      PR according to the four-scaled, increasing disease severity criteria by Rud et
      al. (International Journal of Oral Surgery, 1, 1972 and 195) and Molven et al.
      (International Journal of Oral and Maxillofacial Surgery, 16, and 432):
      'Radiographic assessment A'. By including clinical information 'Treatment plan A'
      was made as follows: 1) no treatment, 2) further observation, 3) SER reoperation
      (SER-R), or 4) extraction. Hereafter, the CBCT volume was assessed and the
      information incorporated for 'Radiographic assessment B' followed by 'Treatment
      plan B'. Agreement between radiographic assessments and between treatment plans
      was recorded and assessed statistically by Stuart-Maxwell test for marginal
      homogeneity. RESULTS: Nine teeth had been extracted; thus, the final analysis
      included 74 teeth (66 patients). The radiographic assessment was changed as a
      result of the CBCT evaluation in 38 cases (51.4%), of which 35 (47.3%) were to a
      higher Rud & Molven score, P < 0.001. The treatment plan was changed for 18 teeth
      (24.3%). For 14 teeth (18.9%), the change was from no treatment or further
      observation to a more invasive treatment plan (SER-R or extraction), P = 0.005.
      CONCLUSION: The use of CBCT for long-term follow-up after SER led to more cases
      diagnosed with persisting or recurrent apical periodontitis and hence often to
      the recommendation of a more invasive treatment modality.

PMID- 29345850
TI  - Effects of glutaraldehyde-didecyldimethylammonium bromide combined disinfectant
      on the cell surface of Staphylococcus aureus.
AB  - AIMS: The effects of a new glutaraldehyde-didecyldimethylammonium bromide
      combination disinfectant (GD) on the cell surface of Staphylococcus aureus, a
      representative Gram-positive bacterium, were investigated in this study. METHODS
      AND RESULTS: Results of bacterial surface structural analysis showed that GD
      significantly changed the bacterial morphology. The membrane fluidity decreased
      and outer membrane permeabilization increased after contact with GD. Furthermore,
      the integrity of the cytoplasmic membrane was destroyed by over 99% after
      exposure to GD for a short time. Bacterial ATPase activity correlated negatively
      with the treatment of GD over time, and proteins were degraded. Assays of
      intracellular component leakage indicated that GD caused the rapid leakage of K+
      , Mg2+ , ATP molecules, and proteins into the extracellular environment.
      CONCLUSIONS: The effects of GD against S. aureus are probably attributable to the
      removal of the permeability barrier, changes in the S. aureus morphology, changes
      in the structures and functions of the cell membrane, leakage of intracellular
      substances and disturbance of the intracellular homeostasis. As a result, this
      irreversible damage accelerated the death of S. aureus. SIGNIFICANCE AND IMPACT
      OF THE STUDY: In an earlier study, the bactericidal mechanism of GD against
      Escherichia coli was investigated. Hence, this study focused on the action of
      mechanism of GD against S. aureus. It is important to clarify the disinfectant
      bactericidal mechanisms of GD against bacterium, in general, and this study
      provides theoretical support to the prevention of bacterial resistance.

PMID- 29345851
TI  - The immunosuppressive effects of CD4+ CD25+ regulatory T cells on dendritic cells
      in patients with chronic hepatitis B.
AB  - The characteristics and functions of CD4+ CD25+ regulatory T cells (Tregs) have
      been well defined in murine and human systems. However, the interaction or
      crosstalk between CD4+ CD25+ Tregs and dendritic cells (DCs) remains
      controversial. In this study, the effects of chronic hepatitis B (CHB) CD4+ CD25+
      Tregs on the maturation and function of monocyte-derived DCs were examined. The
      results showed that CD4+ CD25+ render the DCs inefficient as antigen-presenting
      cells (APCs) despite prestimulation with CD40 ligand. This effect was marginally
      reverted by applying neutralizing antibodies (Abs) to IL-10 and TGF-beta. There
      were an increased IL-10 and TGF-beta secretion and reduced expression of
      costimulatory molecules in DC. Thus, in addition to a direct suppressor effect on
      CD4+ T cells, CD4+ CD25+ may modulate the immune response through DCs in CHB
      patients.

PMID- 29345853
TI  - Any Associations Between the Timing of the Peak QTc Prolongation, Depth of the
      Admission T-Wave Inversions, and Extent/Intensity of Myocardial Edema in Patients
      With Takotsubo Syndrome?

PMID- 29345852
TI  - Cadmium and cadmium-tolerant soil bacteria in cacao crops from northeastern
      Colombia.
AB  - AIMS: This research aims to assess total-cadmium soil content and microbiological
      aspects to understand the dynamics of culturable cadmium-tolerant bacteria (CdtB)
      in cacao soils from northeastern Colombia. METHODS AND RESULTS: An integration of
      inverted dish plating, Cd determination and a microcalorimetry assay (IMC) was
      carried out. A farm in Boyaca showed the highest level of total soil Cd (3.74 mg
      kg-1 ) followed by farms in Santander and Arauca (2.76 and 1.16 mg kg-1 ,
      respectively). Coefficient of determination between total soil Cd and CFU of CdtB
      was high (R2  = 0.83) for the farm in Boyaca. Moreover, a pool of 129 CdtB was
      isolated, and phylogeny of 21 CdtB was discussed. Among CdtB strains isolated,
      Enterobacter sp. CdDB41 showed major Cd immobilization capacity (Qmax of 2.21 and
      2.32 J at 6 and 24 mg l-1 of CdCl2 ), with an immobilization rate of 0.220 mg kg
      1  h-1 . CONCLUSIONS: Among CdtB strains isolated, Enterobacter sp. CdDB41 showed
      major Cd immobilization capacity (Qmax of 2.21 and 2.32 J at 6 and 24 mg l-1 of
      CdCl2 ), with an immobilization rate of 0.220 mg kg-1  h-1 . SIGNIFICANCE AND
      IMPACT OF THE STUDY: Nothing is known about soil CdtB in cacao. Our data showed
      that CdtB such as Enterobacter sp. has high immobilization capacity. Furthermore,
      the otavite found in situ might be mineralized due to the bacterial metabolic
      activity of CdtB.

PMID- 29345854
TI  - [CH3 NH3 ]4 Ga4 SbS9 S0.28 O0.72 H: A Three-Dimensionally Open-Framework
      Heterometallic Chalcogenidoantimonate Exhibiting Ni2+ Ion-Exchange Property.
AB  - An open-framework chalcogenidoantimonate, namely, [CH3 NH3 ]4 Ga4 SbS9 S0.28
      O0.72 H (1), has been solvothermally synthesized and structurally characterized.
      Interestingly, 1 showed Ni2+ ion-exchange properties and wide pH resistance, with
      a maximum exchange capacity of 76.9 mg g-1 . To the best of our knowledge, this
      is the first example of amine-directed three-dimensional (3D) heterometallic
      chalcogenidometalates for highly selective Ni2+ ion capture with a high
      distribution coefficient (Kd =1.65*105  mL g-1 ).

PMID- 29345856
TI  - Response to Teng et al.

PMID- 29345855
TI  - Increased oestradiol in hepatitis E virus-infected pregnant women promotes viral
      replication.
AB  - Hepatitis E virus (HEV) infection causes subclinical diseases, leading to high
      mortality (>25%) in pregnant women. HEV replication is aggressively escalated in
      pregnant women, especially in the third trimester of pregnancy. Oestrogen plays
      an important role in pregnancy. However, the pathogenesis of HEV in pregnant
      women or immunosuppressive pregnant women (such as HIV-infected or organ
      transplanted pregnant women) remains unclear. We investigated the role of
      oestradiol in HEV infection in a cell culture system. HEV-infected pregnant women
      had significantly higher oestradiol levels compared with uninfected individuals.
      HEV infection was significantly increased in cells treated with analogues of
      oestradiol, diethylstilbestrol (DES) or 17beta-oestradiol in a dose-dependent
      way. However, tamoxifen, an antagonist oestrogen, inhibited HEV replication. HEV
      infection inhibits oestrogen receptor (ER-alpha) expression. Immunofluorescence
      and co-immunoprecipitation assays indicated that ER-alpha interacted with the
      helicase of HEV ORF1 indirectly. More importantly, HEV infection was exacerbated
      in immunosuppressive cells treated with an inhibitor of PI3K-AKT-mTOR signal
      pathway (LY296004) and supplemented with pregnant women serum with high
      oestradiol simultaneously. These results strongly suggest that pregnant women
      with high oestradiol and/or immunosuppression will be vulnerable to HEV
      infection.

PMID- 29345857
TI  - News from the European Academy of Andrology (EAA).

PMID- 29345858
TI  - Cardiopulmonary fitness is strongly associated with body cell mass and fat-free
      mass: The Study of Health in Pomerania (SHIP).
AB  - Peak oxygen uptake (VO2peak) is commonly indexed by total body weight (TBW) to
      determine cardiopulmonary fitness (CPF). This approach may lead to
      misinterpretation, particularly in obese subjects. We investigated the
      normalization of VO2peak by different body composition markers. We analyzed
      combined data of 3848 subjects (1914 women; 49.7%), aged 20-90, from two
      independent cohorts of the population-based Study of Health in Pomerania (SHIP-2
      and SHIP-TREND). VO2peak was assessed by cardiopulmonary exercise testing. Body
      cell mass (BCM), fat-free mass (FFM), and fat mass (FM) were determined by
      bioelectrical impedance analysis. The suitability of the different markers as a
      normalization variable was evaluated by taking into account correlation
      coefficients (r) and intercept (alpha-coefficient) values from linear regression
      models. A combination of high r and low alpha values was considered as preferable
      for normalization purposes. BCM was the best normalization variable for VO2peak
      (r = .72; P <= .001; alpha-coefficient = 63.3 mL/min; 95% confidence interval
      [CI]: 3.48-123) followed by FFM (r = .63; P <= .001; alpha-coefficient = 19.6
      mL/min; 95% CI: -57.9-97.0). On the other hand, a much weaker correlation and a
      markedly higher intercept were found for TBW (r = .42; P <= .001; alpha
      coefficient = 579 mL/min; 95% CI: 483 to 675). Likewise, FM was also identified
      as a poor normalization variable (r = .10; P <= .001; alpha-coefficient = 2133;
      95% CI: 2074-2191). Sex-stratified analyses confirmed the above order for the
      different normalization variables. Our results suggest that BCM, followed by FFM,
      might be the most appropriate marker for the normalization of VO2peak when
      comparing CPF between subjects with different body shape.

PMID- 29345859
TI  - Development of a risk prediction model for lung cancer: The Japan Public Health
      Center-based Prospective Study.
AB  - Although the impact of tobacco consumption on the occurrence of lung cancer is
      well-established, risk estimation could be improved by risk prediction models
      that consider various smoking habits, such as quantity, duration, and time since
      quitting. We constructed a risk prediction model using a population of 59 161
      individuals from the Japan Public Health Center (JPHC) Study Cohort II. A
      parametric survival model was used to assess the impact of age, gender, and
      smoking-related factors (cumulative smoking intensity measured in pack-years, age
      at initiation, and time since cessation). Ten-year cumulative probability of lung
      cancer occurrence estimates were calculated with consideration of the competing
      risk of death from other causes. Finally, the model was externally validated
      using 47 501 individuals from JPHC Study Cohort I. A total of 1210 cases of lung
      cancer occurred during 986 408 person-years of follow-up. We found a dose
      dependent effect of tobacco consumption with hazard ratios for current smokers
      ranging from 3.78 (2.00-7.16) for cumulative consumption <=15 pack-years to 15.80
      (9.67-25.79) for >75 pack-years. Risk decreased with time since cessation. Ten
      year cumulative probability of lung cancer occurrence estimates ranged from 0.04%
      to 11.14% in men and 0.07% to 6.55% in women. The model showed good predictive
      performance regarding discrimination (cross-validated c-index = 0.793) and
      calibration (cross-validated chi2 = 6.60; P-value = .58). The model still showed
      good discrimination in the external validation population (c-index = 0.772). In
      conclusion, we developed a prediction model to estimate the probability of
      developing lung cancer based on age, gender, and tobacco consumption. This model
      appears useful in encouraging high-risk individuals to quit smoking and undergo
      increased surveillance.

PMID- 29345860
TI  - Reply to 'Mucosal ischemia and bowel gangrene can have different treatment
      options in sigmoid volvulus'.

PMID- 29345862
TI  - Thirty Great Years.

PMID- 29345861
TI  - Ruthenium-Catalyzed Aerobic Oxidation of Amines.
AB  - Amine oxidation is one of the fundamental reactions in organic synthesis as it
      leads to a variety of value-added products such as oximes, nitriles, imines, and
      amides among many others. These products comprise the key N-containing building
      blocks in the modern chemical industry, and such transformations, when achieved
      in the presence of molecular oxygen without using stoichiometric oxidants, are
      much preferred as they circumvent the production of unwanted wastes. In parallel,
      the versatility of ruthenium catalysts in various oxidative transformations is
      well-documented. Herein, this review focuses on aerobic oxidation of amines
      specifically by using ruthenium catalysts and highlights the major achievements
      in this direction and challenges that still need to be addressed.

PMID- 29345863
TI  - All Good Things....

PMID- 29345864
TI  - Naltrexone and Disulfiram Treatment Response in Veterans With Alcohol Dependence
      and Co-Occurring Problem-Gambling Features.
AB  - BACKGROUND: Disordered gambling behavior frequently co-occurs with alcohol
      dependence and other psychiatric conditions. Using data from a previously
      published trial, we conducted secondary analyses to examine the influence of
      problem-gambling features on treatment outcome for alcohol dependence or co
      occurring psychopathology assessed via DSM-IV criteria. METHODS: Two hundred
      fifty-four patients with alcohol dependence and co-occurring psychiatric
      disorders were treated for 12 weeks in an outpatient medication study conducted
      at 3 Veterans Administration outpatient clinics from October 1998 to March 2002.
      Randomization included assignment to 1 of 4 groups: (1) naltrexone alone, (2)
      placebo alone, (3) (open-label) disulfiram and (blinded) naltrexone, or (4) (open
      label) disulfiram and (blinded) placebo. One hundred seventy-four participants
      were evaluated for the diagnostic inclusionary criteria for pathological gambling
      using the Massachusetts Gambling Screen. Primary outcome and secondary outcome
      measures assessed alcohol use and psychiatric domains. RESULTS: Forty-five of 174
      participants (25.9%) exhibited problem-gambling features (acknowledged 1 or more
      inclusionary criteria for pathological gambling). A gambling-group-by-disulfiram
      interaction was observed for abstinence, with problem-gambling features not
      associated with beneficial response to disulfiram (z = 6.58, P = .01).
      Participants with problem-gambling features reported significantly less
      improvement over time in general psychiatric functioning (z = 2.62, P = .01),
      specifically within somatization (z = 3.77, P < .01), phobic anxiety (z = 3.24, P
      < .01), interpersonal sensitivity (z = 2.61, P = .01), paranoid ideation (z =
      2.32, P = .02), and anxiety (z = 2.10, P = .04) domains. CONCLUSIONS: The
      association between problem-gambling features and poorer outcomes in alcohol and
      multiple nonsubstance psychiatric domains suggests the need for improved
      screening for gambling problems in dually diagnosed populations and for the
      development of empirically validated treatments for individuals with these
      disorders.

PMID- 29345865
TI  - The Few Who Served Deserved to Be Cared For.

PMID- 29345866
TI  - Cognitive Impairment in Patients With Depression: Awareness, Assessment, and
      Management.
AB  - Cognitive impairment is a common, often persistent, symptom of major depressive
      disorder (MDD) that is disproportionately represented in patients who have not
      returned to full psychosocial functioning. The ultimate goal of treatment in
      depression is full functional recovery, and assessing patients for cognitive
      impairment and selecting treatments that address cognitive dysfunction should
      lead to improved functional outcomes. Unfortunately, many clinicians use
      screening and assessment tools that are not suited for measuring cognitive
      impairment in patients with depression. The new THINC-it assessment tool is the
      first instrument that provides objective and subjective data on dysfunction in
      all the cognitive domains commonly affected by depression. In regard to
      treatment, several pharmacologic and nonpharmacologic interventions have been
      investigated as treatments for cognitive dysfunction in individuals with MDD.
      However very few studies of treatments for cognitive function in patients with
      MDD have been adequate, in terms of sample size and study methods, to guide
      clinical practice. The best evidence supports the moderate efficacy of some
      antidepressants, cognitive-behavioral therapy, and exercise. .

PMID- 29345867
TI  - Findings of Interest.

PMID- 29345868
TI  - The Gap Between the Randomized Controlled Trial-Based Evidence and Real-World
      Practice in Switching Strategies of Major Depressive Disorder.

PMID- 29345869
TI  - Drs Bschor and Baethge Reply.

PMID- 29345870
TI  - Antidepressant Response and Dissociative Effects After Ketamine Treatment: Two
      Sides of the Same Coin?

PMID- 29345871
TI  - Dr Andrade Replies.

PMID- 29345872
TI  - Cognitive Planning Neural Correlates in a Pediatric Monozygotic Twin Pair
      Discordant for Obsessive-Compulsive Disorder: Exploring Potential Application in
      Precision Medicine.

PMID- 29345874
TI  - Epidemiology and Prevention of Tardive Dyskinesia.
AB  - What risk factors suggest that patients are more likely to develop tardive
      dyskinesia (TD)? Can TD symptoms be prevented? Read this CME activity to learn
      about the prevalence, epidemiology, and prevention of these abnormal movements
      from an expert.

PMID- 29345873
TI  - Patient Education in Psychopharmacology and the Risk of Nocebo-Related Treatment
      Inefficacy and Harm.
AB  - Many studies have shown that educating patients about the potential adverse
      effects of a drug can increase the chances that those adverse effects will be
      experienced. Studies have further shown that how such information is communicated
      can also impact this nocebo risk. Additionally, information provided through
      patient education can influence treatment efficacy, perhaps by moderating the
      placebo response. There is therefore a need to optimize the manner in which
      patients are educated about their medications so that placebo-related benefits
      are enhanced and nocebo-related harm is minimized. This article provides
      suggestions on the subject for clinical practice as well as research. Nonspecific
      factors in psychopharmacology are important and should not be neglected.

PMID- 29345875
TI  - Available Tools for Assessing Cognitive Impairment in Major Depressive Disorder.
AB  - You know that measuring cognition in your patients with depression is important.
      But cognitive assessment instruments can be difficult to access, expensive, time
      consuming, and not available in an electronic format. Read this CME activity to
      learn about a new free tool.

PMID- 29345876
TI  - Assessing Patients for Tardive Dyskinesia.
AB  - Do you regularly screen for tardive dyskinesia in at-risk patients? Explore this
      CME activity by a well-known expert for information on rating scales for
      screening, available diagnostic criteria, assessment tips, and monitoring
      recommendations.

PMID- 29345877
TI  - Comparing Treatments for Tardive Dyskinesia.
AB  - Many treatment interventions for tardive dyskinesia have been studied, but some
      have better evidence than others. Read this CME activity to get an expert's
      perspectives on the evidence for older and newer treatments so that you can
      minimize abnormal movements in your patients.

PMID- 29345878
TI  - Impact of Cognitive Impairment on Functioning in Patients With Depression.
AB  - Reassessing a patient's diagnosis if he or she does not respond adequately to
      initial antidepressant pharmacotherapy is imperative. In this CME activity,
      evaluate the case of Melissa, a 32-year-old architect with a potential case of
      treatment-resistant depression, and decide on appropriate treatment strategies.

PMID- 29345879
TI  - Improving Long-Term Outcomes in Patients With Schizophrenia: What Is the Evidence
      for Long-Acting Injectable Antipsychotics?
AB  - Do you consider long-acting injectable (LAI) antipsychotics when selecting among
      treatments for schizophrenia? Take part in this CME activity to review the
      evidence for LAIs vs oral medications and to learn which patients may benefit
      most from this treatment option. Plus, discover the pharmacokinetic properties of
      LAIs and barriers to their use.

PMID- 29345880
TI  - Strategies for Managing Patients With Depression Who Are Experiencing Cognitive
      Impairment.
AB  - Pronounced deficits in executive function are found in up to one-third of
      patients with MDD, and this impairment can keep patients from achieving full
      functional recovery. In this CME activity, review the evidence regarding the
      effectiveness of available interventions to improve cognitive dysfunction in
      patients with MDD.

PMID- 29345881
TI  - Noninferiority Trials.

PMID- 29345882
TI  - Improvement of Antitumor Efficacy by Combination of Thermosensitive Liposome with
      High-Intensity Focused Ultrasound.
AB  - High intensity focused ultrasound (HIFU), allowing for precise heating of the
      deep and local area, is emerging as the source of mild hyperthermia for delivery
      of doxorubicin (DOX) using thermosensitive liposomes (TSLs). Conventionally, HIFU
      has been used for intravascular drug release at tumor tissue by inducing mild
      hyperthermia immediately upon systemic administration of DOX-TSLs. This immediate
      heating approach (IHA), however, limits the deep penetration of DOX for high
      anticancer efficacy. In an attempt to maximize the accumulation of DOX at tumor,
      the delayed heating approach (DHA) has been explored. In this approach, DOX-TSLs
      were intravenously administered into the tumor-bearing mice after pre-treatment
      of tumor tissue with HIFU to increase vascular permeability. We developed the
      fatty acid-cojugated elastinlike polypeptide bearing TSL (FTSL). The DOX-loaded
      FTSLs had a hydrodynamic size of 142 nm. In vivo biodistribution study
      demonstrated that DOX-FTSLs were selectively accumulated at tumor tissue with the
      maximum amount of DOX at 6 h post-injection. Thereafter, the tumor tissue was
      heated to 42  degrees C to induce rapid release of DOX from FTSLs. The results
      have demonstrated that, compared to IHA, DHA significantly enhances the antitumor
      efficacy of DOX-FTSLs because of their effective penetration to tumor tissue via
      the enhanced permeation retention effect, followed by rapid release of DOX.

PMID- 29345883
TI  - Crisis in the Sustainability of the U.S. Blood System.

PMID- 29345884
TI  - Crisis in the Sustainability of the U.S. Blood System.

PMID- 29345885
TI  - Superparamagnetic Iron Oxide Nanorod Carriers for Paclitaxel Delivery in the
      Treatment and Imaging of Colon Cancer in Mice.
AB  - A multifunctional magnetic drug delivery system was developed and explored as an
      efficient and less invasive technique to improve colon cancer diagnosis and
      therapy in mice. In this system, superparamagnetic iron oxide nanorod cores
      enhanced passive targeting by bandaging a magnet adjacent to the tumor site,
      whereas pluronic F127 shell acted as the carrier for paclitaxel. The pluronic
      conjugated superparamagnetic iron oxide cores were prepared using the
      hydrothermal method. It was found that the initial pluronic concentration exerted
      a significant effect on the distribution of the diameters and lengths of the
      nanorods. Despite the variation in pluronic concentrations and dimensions of iron
      oxide products, all the samples exhibited negligible coercivity and remanence,
      confirming their superparamagnetic characteristics. The pluronic F127
      superparamagnetic iron oxide nanocarriers were then prepared by encapsulation of
      nanorods into pluronic micelles and assessed for paclitaxel loading. Results
      showed that paclitaxel was incorporated into the core of the micelles through
      hydrophobic interactions, and that elevating both paclitaxel concentration and
      temperature increased the loading efficiency. The therapeutic effect of
      paclitaxel-loaded nanocarriers was then tested in in vitro and in vivo colon
      cancer models. Compared to docetaxel, the paclitaxel-loaded magnetic nanocarriers
      significantly suppressed tumor growth and improved survival time of xenograft
      mice. The accumulated magnetic nanocarriers inside the tumor also served as a
      contrast agent and enhanced magnetic resonance imaging localization and
      visualization of the small tumor.

PMID- 29345886
TI  - Curcumin-Zein Nanospheres Improve Liver Targeting and Antifibrotic Activity of
      Curcumin in Carbon Tetrachloride-Induced Mice Liver Fibrosis.
AB  - Liver fibrosis is a major health problem that has no satisfactory medication.
      Curcumin, (CUR) although known for its antifibrotic activity, has limited
      medicinal use owing to its poor oral pharmacokinetic properties and targeting
      efficiency. The current study aimed at exploring the ability of zein (ZN)
      nanospheres to improve the liver targeting and antifibrotic activity of CUR in a
      mouse model of carbon tetrachloride (CCl4)-induced liver fibrosis. Four different
      formulae of ZN-loaded CUR were prepared and examined in terms of particle size,
      zeta potential, encapsulation efficiency, and in vitro permeation. The formula
      containing a CUR to ZN ratio of 1:3 showed optimum nanosphere properties and was
      subjected to further investigations. Under a scanning electron microscope, the
      selected formula showed spherical particles with uniform size distribution. In
      normal mice, the selected formula exhibited improved bioavailability and liver
      targeting efficiency compared to raw CUR. The nanosphere preparation also offered
      significant protection against CCl4-induced liver function deterioration,
      histopathological changes, and oxidative stress in mice. Compared to raw CUR, CUR
      ZN was significantly more effective in attenuating the rise in hepatic gene
      expression of collagen-1, tissue inhibitor of metalloproteinase-2, and
      transforming growth factor beta, as well as the downregulation of matrix
      metalloproteinase-2 expression. Masson's trichrome staining confirmed the higher
      antifibrotic activity of the nanospheres that ameliorated the rise in hepatic
      hydroxyproline content and collagen-1-immunopositive areas in mice liver
      sections. In conclusion, CUR-ZN nanospheres demonstrated improved liver targeting
      efficiency and antifibrotic activity in comparison to raw CUR in CCl4-induced
      liver fibrosis in mice.

PMID- 29345887
TI  - Nanotheranostic Based Iron Oxide (Fe3O4) Saturated Lactoferrin Nanocapsules for
      Colonic Adenocarcinoma.
AB  - Efficient early detection of cancer and its simultaneous therapy can improve the
      survival of cancer patients significantly. Recently there is great interest for
      the development of nanotheranostic systems with multimodal live real-time imaging
      ability. Novel multimodal multifunctional iron oxide (Fe3O4) saturated
      lactoferrin (FebLf) nanocapsules/nanocarriers (FebLf NCs) nanoformulation was
      fabricated. Anti-cancer nanotheranostic ability in human xenograft colonic
      adenocarcinoma model was conducted in vivo by employing near infrared
      flouroscence (NIRF) real time live mice imaging technology. FebLf NCs showed
      spherical morphology with 50 to 80 nm size with super paramagnetic property and
      exhibited profound in vivo anti-tumour efficacy, leading to regression of the
      xenograft colonic tumour growth over a 90 day trial period. NIRF real time
      imaging revealed selective localisation patterns of the FebLf NCs at the tumour
      site causing tumour growth inhibition. In turn, ex vivo NIRF imaging of mice
      organs showed enhanced tumoural uptake and biodistribution at the vital organs
      including spleen, intestine, kidney, and intestine. Low-density lipoprotein
      receptors (LDLRs), ferroportin, ferritin receptor based in vivo internalisation
      mechanisms and iron metabolism regulation were observed. Histopathological
      analysis revealed obsolute non-toxic nature of FebLf NCs in mice tissues. These
      observations summate biocompatible, multimodal anticancer activity of novel FebLf
      NCs for real time cancer therapeutic imaging leading to targeted colonic
      adenocarcinoma therapy.

PMID- 29345888
TI  - Nanoparticles with Optimal Ratiometric Co-Delivery of Docetaxel with Gambogic
      Acid for Treatment of Multidrug-Resistant Breast Cancer.
AB  - It has been reported that gambogic acid (GA), the main active component of
      gamboge, could directly inhibit and reduce the expression level of P-gp by
      promoting protein degradation through post-translational proteasome pathway. In
      this study, the optimal molar ratio of GA/docetaxel (DTX) that could recover the
      sensitivity of MCF-7/ADR cells to DTX was firstly investigated. Then GA and DTX
      were loaded simultaneously in PLGA nanoparticles in terms of the optimal ratio.
      In vitro cell apoptosis and western-blot assays showed that co-delivery of
      anticancer drugs resulted in enhanced cell apoptosis through the downregulation
      of the expression level of P-gp. Interestingly, in vivo pharmacokinetic study
      demonstrated that GA and DTX are released synchronously in blood from the NPs.
      Finally, the most effective tumor growth inhibition in the MCF-7/ADR human breast
      tumor xenograft was observed in the co-delivery nanoparticle formulation group in
      comparison with saline control, free DTX solution and free DTX/GA solution. Taken
      together, our study demonstrated that DTX/GA PLGA NPs based combination therapy
      holds significant potential towards the treatment of multidrug-resistant breast
      cancer.

PMID- 29345889
TI  - Modulation of MicroRNAs 34a and 21 Affects Viability, Senescence, and Invasion in
      Glioblastoma Multiforme.
AB  - Glioblastoma multiforme (GBM) is an aggressive and invasive brain tumor. Current
      interventional strategies have been minimally successful. Three key
      characteristics of GBMs are (1) enhanced resistance to apoptosis, (2) increased
      proliferation rate, and (3) increased invasion potential, making them difficult
      to treat. MicroRNAs (miRs) have demonstrated beneficial therapeutic intervention;
      particularly miRs 34a and 21, which have been implicated in regulation of
      apoptosis, senescence, and invasion of GBM tumor cells. MiR21 is anti-apoptotic
      and pro-proliferative, whereas miR34a is proapoptotic and an anti-invasive
      regulator in tumor cells. Our study investigates the effects of modulating both
      miR34a and miR21, in addition to comparing the two individual treatments. Using
      targeted cationic liposomes that bind to the epidermal growth factor receptor
      (EGFR), we delivered miR34a and/or anti-sense oligonucleotide to miR21 (ASO21) to
      GBM tumor cell lines, U87MG and A172, in vitro. Our data demonstrate that co
      delivery of miR34a and ASO21 results in enhanced reduction in viability and
      invasion, while increasing senescence in vitro. Additionally, there were
      significant decreases in pro-invasion and -proliferation gene markers, as well as
      an increase in pro-apoptotic markers. In vivo results demonstrate that the
      combination of miR34a and ASO21 reduced tumor volume and proliferation of the
      A172 tumor cells. Accumulation of rhodamine encapsulated EGFR-targeted cationic
      liposomes was observed throughout the primary tumor bed after systemic injection.
      To our knowledge, we are the first to modulate multiple miRs, while using a
      targeted cationic liposomal delivery for miR-based therapy. These results
      demonstrate a potential clinically relevant, miR therapeutic strategy for GBM.

PMID- 29345890
TI  - How Medicare Could Provide Dental, Vision, and Hearing Care for Beneficiaries.
AB  - Issue: The Medicare program specifically excludes coverage of dental, vision, and
      hearing services. As a result, many beneficiaries do not receive necessary care.
      Those that do are subject to high out-of-pocket costs. Goal: Examine gaps in
      access to dental, vision, and hearing services for Medicare beneficiaries and
      design a voluntary dental, vision, and hearing benefit plan with cost estimates.
      Methods: Uses the Medicare Current Beneficiary Survey, Cost and Use File, 2012,
      with population and costs projected to 2016 values. Findings and Conclusions:
      Among Medicare beneficiaries, 75 percent of people who needed a hearing aid did
      not have one; 70 percent of people who had trouble eating because of their teeth
      did not go to the dentist in the past year; and 43 percent of people who had
      trouble seeing did not have an eye exam in the past year. Lack of access was
      particularly acute for poor beneficiaries. Because few people have supplemental
      insurance covering these additional services, among people who received care,
      three-fourths of their costs of dental and hearing services and 60 percent of
      their costs of vision services were paid out of pocket. We propose a basic
      benefit package for dental, vision, and hearing services offered as a premium
      financed voluntary insurance option under Medicare. Assuming the benefit package
      could be offered for $25 per month, we estimate the total coverage costs would be
      $1.924 billion per year, paid for by premiums. Subsidies to reach low-income
      beneficiaries would follow the same design as the Part D subsidy.

PMID- 29345891
TI  - Rapid and Sensitive Fusion Gene Detection in Prostate Cancer Urinary Specimens by
      Label-Free Surface-enhanced Raman Scattering.
AB  - Recurrent chromosomal rearrangements such as fusion genes are associated with
      cancer initiation and progression. Prostate cancer (PCa) is a leading cause of
      cancer-related deaths in men and the TMPRSS2-ERG gene fusion is a recurrent
      biomarker in about 50% of all prostate cancers. However, current screening tools
      for TMPRSS2-ERG are generally confined to research settings and hence, the
      development of a rapid, sensitive and accurate assay for TMPRSS2-ERG detection
      may aid in clinical PCa diagnosis and treatment. Herein, we described a new
      strategy for non-invasive TMPRSS2-ERG detection in patient urinary samples by
      coupling of isothermal reverse transcription-recombinase polymerization
      amplification (RT-RPA) to amplify TMPRSS2-ERG transcripts and surface-enhanced
      Raman scattering (SERS) to directly detect the amplicons. This novel coupling of
      both techniques allows rapid and quantitative TMPRSS2-ERG detection. Our assay
      can specifically detect as low as 103 copies input of TMPRSS2-ERG transcripts and
      was successfully applied to clinical PCa urinary samples. Hence, we believe our
      assay is a potential clinical screening tool for TMPRSS2-ERG in PCa and may have
      broad applications in detecting other gene fusion transcripts in other diseases.

PMID- 29345892
TI  - Colistin-Functionalized Nanoparticles for the Rapid Capture of Acinetobacter
      baumannii.
AB  - Gold nanoparticles (AuNPs) were functionalized for rapid binding of Acinetobacter
      baumannii (A. baumannii), a Gram-negative bacterium. AuNPs were functionalized
      with colistin (Col), a polycationic antibiotic, using a two-step self-assembly
      process, in which heterobifunctional polyethylene glycol (PEG) was used as a
      linker. Colistin was successfully conjugated to the AuNPs (Col-PEG-AuNP), as
      validated by dynamic light scattering (DLS) and proton nuclear magnetic resonance
      (H1 NMR). High angle annular dark field scanning transmission electron microscopy
      (HAADF-STEM) images, acquired simultaneously with X-ray energy dispersive
      spectroscopy (EDS) data, confirmed binding of Col-PEG-AuNPs to the cell envelope
      of A. baumannii. Results generated from a binding assay indicated that Col-PEG
      AuNP complexation with A. baumannii occurred rapidly and reached half-maximum
      saturation in approximately 7 minutes, on average, for all A. baumannii strains
      evaluated. Quantitative measurement of the kinetics of Col-PEG-AuNP binding to A.
      baumannii is essential to inform the design of colistin-functionalized magnetic
      nanoparticles for magnetic separation of nanoparticle-bound A. baumannii.

PMID- 29345893
TI  - Fullerene C60 Derivatives Attenuated Microglia-Mediated Prion Peptide
      Neurotoxicity.
AB  - Prion disorders are progressive neurodegenerative diseases characterized by
      extensive neuronal loss, which is linked to the extracellular accumulation of the
      scrapie isoform (PrPSC) of the normal cellular prion protein (PrPC). As
      microglial activation is a central event in pathogenesis of prion disease, the
      strategies that reduce microglial activation may have therapeutic benefits. In
      this study, the neuroprotective effects of hydroxylated C60(C60-OH) and amino
      modified-C60(C60-NH2) were evaluated by using PrP(106-126)-stimulated BV-2 cells
      as a model of activated microglia. Herein, we showed that microglial activation
      in response to PrP(106-126) was effectively attenuated by pretreatment with C60
      OH as compared with C60-NH2. C60-OH significantly inhibited the excessive
      production of inflammatory mediators, such as prostaglandin E2 (PGE2), nitric
      oxide (NO), tumor necrosis factors (TNF)-alpha, interleukin (IL)-1beta, and IL-6,
      and blocked the expression of cyclooxygenase-2 (COX-2) and inducible nitric-oxide
      synthase (iNOS) in PrP(106-126)-stimulated BV-2 cells. C60-OH exerted anti
      inflammatory potential by up-regulating the expression of antioxidant enzymes via
      activation of nuclear factor erythroid 2-related factor 2 (Nrf2). The inhibitory
      effect of C60-OH against PrP(106-126)-induced inflammatory response was abolished
      by siRNA of Nrf2. In addition, conditioned culture media taken from PrP(106-126)
      stimulated microglia cause apoptotic neuronal cell death, which was suppressed by
      pretreatment with C60-OH. Take together, these results suggest that C60-OH
      protects neuronal cells against PrP(106-126)-mediated neurotoxicity through
      activation of Nrf2 pathway, and provides evidence that fullerene derivatives may
      have therapeutic potential in prion diseases.

PMID- 29345894
TI  - High-Bandwidth White-Light System Combining a Micro-LED with Perovskite Quantum
      Dots for Visible Light Communication.
AB  - This work proposes a high-bandwidth white-light system consisting of a blue
      gallium nitride (GaN) micro-LED (MULED) exciting yellow-emitting CsPbBr1.8I1.2
      perovskite quantum dots (YQDs) for high-speed real-time visible light
      communication (VLC). The packaged 80 MUm * 80 MUm blue-emitting MULED has a
      modulation bandwidth of ~160 MHz and a peak emission wavelength of ~445 nm. The
      achievable bandwidth of the white-light system is up to 85 MHz in the absence of
      filters and equalization technology. Meanwhile, the bandwidth of the YQDs as a
      color converter is as high as 73 MHz with the blue GaN MULED as the pump source.
      A maximum data rate of 300 Mbps can be achieved by taking advantage of the high
      bandwidth of the white-light system using the non-return-to-zero on-off keying
      (NRZ-OOK) modulation scheme. The resultant bit-error rate is 2.0 * 10-3, well
      beneath the forward error correction criterion of 3.8 * 10-3 required for error
      free data transmission. In addition, the YQDs which we proposed as a color
      converter possess high stability for VLC. After half a year, the achievable
      bandwidths of the white-light system and the YQDs are still up to 83 and 70 MHz,
      respectively. This study provides the direction of developing high-bandwidth
      white-light system for both high-efficiency solid-state lighting and high-speed
      VLC.

PMID- 29345895
TI  - Selective Discrimination of Key Enzymes of Pathogenic and Nonpathogenic Bacteria
      on Autonomously Reporting Shape-Encoded Hydrogel Patterns.
AB  - This work reports on a new approach to rapidly and selectively detect and
      discriminate enzymes of pathogenic from those of nonpathogenic bacteria using a
      patterned autonomously reporting hydrogel on a transparent support, in which the
      selectivity has been encoded by the pattern shape to enable facile detection by a
      color change at one single wavelength. In particular, enzyme-responsive chitosan
      hydrogel layers that report the presence of the enzymes beta-glucuronidase (beta
      Gus) and beta-galactosidase (beta-Gal), produced by the nonvirulent Escherichia
      coli K12 and the food-borne biosafety level 3 pathogen enterohemorrhagic E. coli,
      respectively, via the blue color of an indigo dye were patterned by two
      complementary strategies. The comparison of the functionalization of patterned
      chitosan patches on a solid support with two chromogenic substrates on one hand
      and the area-selective conjugation of the substrates on the other hand showed
      that the two characteristic enzymes could indeed be rapidly and selectively
      discriminated. The limits of detection of the highly stable sensing layers for an
      observation time of 60 min using a spectrophotometer correspond to enzyme
      concentrations of beta-Gus and beta-Gal of <=5 and <=3 nM, respectively, and to
      <=62 and <=33 nM for bare eye detection in nonoptimized sensor patches. These
      results confirm the applicability of this approach, which is compatible with the
      simple measurement of optical density at one single wavelength only as well as
      with parallel, multiplexed detection, to differentiate the enzymes secreted by a
      highly pathogenic E. coli from a nonpathogenic E. coli on the basis of
      specifically secreted enzymes. Hence, a general approach for the rapid and
      selective detection of enzymes of different bacterial species for potential
      applications in food safety as well as point-of-care microbiological diagnostics
      is described.

PMID- 29345896
TI  - Correction to Fingerprint Analysis: Moving Toward Multiattribute Determination
      via Individual Markers.

PMID- 29345897
TI  - Design, Synthesis, and Biological Evaluation of 1-Benzylamino-2-hydroxyalkyl
      Derivatives as New Potential Disease-Modifying Multifunctional Anti-Alzheimer's
      Agents.
AB  - The multitarget approach is a promising paradigm in drug discovery, potentially
      leading to new treatment options for complex disorders, such as Alzheimer's
      disease. Herein, we present the discovery of a unique series of 1-benzylamino-2
      hydroxyalkyl derivatives combining inhibitory activity against
      butyrylcholinesterase, beta-secretase, beta-amyloid, and tau protein aggregation,
      all related to mechanisms which underpin Alzheimer's disease. Notably,
      diphenylpropylamine derivative 10 showed balanced activity against both disease
      modifying targets, inhibition of beta-secretase (IC50  hBACE-1 = 41.60 MUM),
      inhibition of amyloid beta aggregation (IC50 Abeta = 3.09 MUM), inhibition of tau
      aggregation (55% at 10 MUM); as well as against symptomatic targets,
      butyrylcholinesterase inhibition (IC50  hBuChE = 7.22 MUM). It might represent an
      encouraging starting point for development of multifunctional disease-modifying
      anti-Alzheimer's agents.

PMID- 29345898
TI  - Engineered Phage Matrix Stiffness-Modulating Osteogenic Differentiation.
AB  - Herein, we demonstrate an engineered phage mediated matrix for osteogenic
      differentiation with controlled stiffness by cross-linking the engineered phage
      displaying Arg-Gly-Asp (RGD) and His-Pro-Gln (HPQ) with various concentrations of
      streptavidin or polymer, poly(diallyldimethylammonium)chloride (PDDA). Osteogenic
      gene expressions showed that they were specifically increased when MC3T3 cells
      were cultured on the stiffer phage matrix than the softer one. Our phage matrixes
      can be easily functionalized using chemical/genetic engineering and used as a
      stem cell tissue matrix stiffness platform for modulating differential cell
      expansion and differentiation.

PMID- 29345899
TI  - Three-Dimensional Graphene Foam-Polymer Composite with Superior Deicing
      Efficiency and Strength.
AB  - The adhesion of ice severely compromises the aerodynamic performance of aircrafts
      operating under critically low-temperature conditions to their surfaces. In this
      study, highly thermally and electrically conductive graphene foam (GrF) polymer
      composite is fabricated. GrF-polydimethylsiloxane (PDMS) deicing composite
      exhibits superior deicing efficiency of 477% and electrical conductivities of 500
      S m-1 with only 0.1 vol % graphene foam addition as compared to other nanocarbon
      based deicing systems. The three-dimensional interconnected architecture of GrF
      allows the effective deicing of surfaces by employing low power densities (0.2 W
      cm-2). Electrothermal stability of the GrF-PDMS composite was proven after
      enduring 100 cycles of the dc loading-unloading current. Moreover,
      multifunctional GrF-PDMS deicing composite provides simultaneous mechanical
      reinforcement by the effective transfer and absorption of loads resulting in a
      23% and 18% increase in elastic modulus and tensile strength, respectively, as
      compared to pure PDMS. The enhanced efficiency of the GrF-PDMS deicing composite
      is a novel alternative to current high-power consumption deicing systems.

PMID- 29345900
TI  - High-Performance Ga2O3 Anode for Lithium-Ion Batteries.
AB  - There is a great deal of interest in developing battery systems that can exhibit
      self-healing behavior, thus enhancing cyclability and stability. Given that
      gallium (Ga) is a metal that melts near room temperature, we wanted to test if it
      could be employed as a self-healing anode material for lithium-ion batteries
      (LIBs). However, Ga nanoparticles (NPs), when directly applied, tended to
      aggregate upon charge/discharge cycling. To address this issue, we employed
      carbon-coated Ga2O3 NPs as an alternative. By controlling the pH of the precursor
      solution, highly dispersed and ultrafine Ga2O3 NPs, embedded in carbon shells,
      could be synthesized through a hydrothermal carbonization method. The particle
      size of the Ga2O3 NPs was 2.6 nm, with an extremely narrow size distribution, as
      determined by high-resolution transmission electron microscopy and Brunauer
      Emmett-Teller measurements. A lithium-ion battery anode based on this material
      exhibited stable charging and discharging, with a capacity of 721 mAh/g after 200
      cycles. The high cyclability is due to not only the protective effects of the
      carbon shell but also the formation of Ga0 during the lithiation process, as
      indicated by operando X-ray absorption near-edge spectroscopy.

PMID- 29345902
TI  - Flexible Amoxicillin-Grafted Bacterial Cellulose Sponges for Wound Dressing: In
      Vitro and in Vivo Evaluation.
AB  - In this study, we report the design and fabrication of a novel biocompatible
      sponge with excellent antibacterial property, making it a promising material for
      wound dressings. The sponge is formed by grafting amoxicillin onto regenerated
      bacterial cellulose (RBC). It was observed that the grafted RBC could enhance the
      antibacterial activity against fungus, Gram-negative, and Gram-positive bacteria.
      The morphology of strains treated with the grafted RBC and fluorescent stain
      results further demonstrated the antibacterial ability of the fabricated sponge.
      Moreover, a cytocompatibility test evaluated in vitro and in vivo illustrates the
      nontoxicity of the prepared sponge. More importantly, the wound infection model
      reveals that this sponge can accelerate the wound healing in vivo. This work
      indicates the novel sponge has the huge potential in wound dressing application
      for clinical use.

PMID- 29345903
TI  - Light-Emitting Diodes Based on Colloidal Silicon Quantum Dots with Octyl and
      Phenylpropyl Ligands.
AB  - Colloidal silicon quantum dots (Si QDs) hold ever-growing promise for the
      development of novel optoelectronic devices such as light-emitting diodes (LEDs).
      Although it has been proposed that ligands at the surface of colloidal Si QDs may
      significantly impact the performance of LEDs based on colloidal Si QDs, little
      systematic work has been carried out to compare the performance of LEDs that are
      fabricated using colloidal Si QDs with different ligands. Here, colloidal Si QDs
      with rather short octyl ligands (Octyl-Si QDs) and phenylpropyl ligands (PhPr-Si
      QDs) are employed for the fabrication of LEDs. It is found that the optical power
      density of PhPr-Si QD LEDs is larger than that of Octyl-Si QD LEDs. This is due
      to the fact that the surface of PhPr-Si QDs is more oxidized and less defective
      than that of Octyl-Si QDs. Moreover, the benzene rings of phenylpropyl ligands
      significantly enhance the electron transport of QD LEDs. It is interesting that
      the external quantum efficiency (EQE) of PhPr-Si QD LEDs is lower than that of
      Octyl-Si QD LEDs because the benzene rings of phenylpropyl ligands suppress the
      hole transport of QD LEDs. The unbalance between the electron and hole injection
      in PhPr-Si QD LEDs is more serious than that in Octyl-Si QD LEDs. The currently
      obtained highest optical power density of ~0.64 mW/cm2 from PhPr-Si QD LEDs and
      highest EQE of ~6.2% from Octyl-Si QD LEDs should encourage efforts to further
      advance the development of high-performance optoelectronic devices based on
      colloidal Si QDs.

PMID- 29345904
TI  - Enzyme-Initiated Quinone-Chitosan Conjugation Chemistry: Toward A General in Situ
      Strategy for High-Throughput Photoelectrochemical Enzymatic Bioanalysis.
AB  - Herein we report a general and novel strategy for high-throughput
      photoelectrochemical (PEC) enzymatic bioanalysis on the basis of enzyme-initiated
      quinone-chitosan conjugation chemistry (QCCC). Specifically, the strategy was
      illustrated by using a model quinones-generating oxidase of tyrosinase (Tyr) to
      catalytically produce 1,2-bezoquinone or its derivative, which can easily and
      selectively be conjugated onto the surface of the chitosan deposited PbS/NiO/FTO
      photocathode via the QCCC. Upon illumination, the covalently attached quinones
      could act as electron acceptors of PbS quantum dots (QDs), improving the
      photocurrent generation and thus allowing the elegant probing of Tyr activity.
      Enzyme cascades, such as alkaline phosphatase (ALP)/Tyr and beta-galactosidase
      (Gal)/Tyr, were further introduced into the system for the successful probing of
      the corresponding targets. This work features not only the first use of QCCC in
      PEC bioanalysis but also the separation of enzymatic reaction from the
      photoelectrode as well as the direct signal recording in a split-type protocol,
      which enables quite convenient and high-throughput detection as compared to
      previous formats. More importantly, by using numerous other oxidoreductases that
      involve quinones as reactants/products, this protocol could serve as a common
      basis for the development of a new class of QCCC-based PEC enzymatic bioanalysis
      and further extended for general enzyme-labeled PEC bioanalysis of versatile
      targets.

PMID- 29345905
TI  - Chelate-Assisted Ring-Closing Metathesis: A Strategy for Accelerating
      Macrocyclization at Ambient Temperatures.
AB  - Ring-closing metathesis (RCM) offers versatile catalytic routes to macrocycles,
      with applications ranging from perfumery to production of antiviral drugs.
      Unwanted oligomerization, however, is a long-standing challenge. Oligomers can be
      converted into the cyclic targets by catalysts that are sufficiently reactive to
      promote backbiting (e.g., Ru complexes of N-heterocyclic carbenes; NHCs), but
      catalyst decomposition limits yields and selectivity. Incorporation of a
      hemilabile o-dianiline (ODA) chelate into new catalysts of the form
      RuCl2(NHC)(ODA)(=CHPh) accelerates macrocyclization, particularly for dienes
      bearing polar sites capable of H-bonding: it may also inhibit catalyst
      decomposition during metathesis. Significant improvements relative to prior Ru
      NHC catalysts result, with fast macrocyclization of conformationally flexible
      dienes at room temperature.

PMID- 29345906
TI  - Prediction of Hot Spots at Myeloid Cell Leukemia-1-Inhibitor Interface Using
      Energy Estimation and Alanine Scanning Mutagenesis.
AB  - Myeloid cell leukemia 1 (Mcl1) is an antiapoptotic protein that plays central
      role in apoptosis regulation. Also, Mcl1 has the potency to resist apoptotic cues
      resulting in up-regulation and cancer cell protection. A molecular probe that has
      the potential to specifically target Mcl1 and thereby provoke its down-regulatory
      activity is very essential. The aim of the current study is to probe the internal
      conformational dynamics of protein motions and potential binding mechanism in
      response to a series of picomolar range Mcl1 inhibitors using explicit-solvent
      molecular dynamics (MD) simulations. Subsequently, domain cross-correlation and
      principal component analysis was performed on the snapshots obtained from the MD
      simulations. Our results showed significant differences in the internal
      conformational dynamics of Mcl1 with respect to binding affinity values of
      inhibitors. Further, the binding free energy estimation, using three different
      samples, was performed on the MD simulations and revealed that the predicted
      energies (DeltaGmmgbsa) were in good correlation with the experimental values
      (DeltaGexpt). Also, the energies obtained using all sampling models were
      efficiently ranked. Subsequently, the decomposition energy analysis highlighted
      the major energy-contributing residues at the Mcl1 binding pocket. Computational
      alanine scanning performed on high energy-contributing residues predicted the hot
      spot residues. The dihedral angle analysis using MD snapshots on the predicted
      hot spot residue exhibited consistency in side chain conformational motion that
      ultimately led to strong binding affinity values. The findings from the present
      study might provide valuable guidelines for the design of novel Mcl1 inhibitors
      that might significantly improve the specificity for new-generation
      chemotherapeutic agents.

PMID- 29345901
TI  - Playing with the Molecules of Life.
AB  - Our understanding of the complex molecular processes of living organisms at the
      molecular level is growing exponentially. This knowledge, together with a
      powerful arsenal of tools for manipulating the structures of macromolecules, is
      allowing chemists to to harness and reprogram the cellular machinery in ways
      previously unimaged. Here we review one example in which the genetic code itself
      has been expanded with new building blocks that allow us to probe and manipulate
      the structures and functions of proteins with unprecedented precision.

PMID- 29345907
TI  - Effects of Plant Sterols or beta-Cryptoxanthin at Physiological Serum
      Concentrations on Suicidal Erythrocyte Death.
AB  - The eryptotic and hemolytic effects of a phytosterol (PS) mixture (beta
      sitosterol, campesterol, stigmasterol) or beta-cryptoxanthin (beta-Cx) at
      physiological serum concentration and their effect against oxidative stress
      induced by tert-butylhydroperoxide (tBOOH) (75 and 300 MUM) were evaluated. beta
      Cryptoxanthin produced an increase in eryptotic cells, cell volume, hemolysis,
      and glutathione depletion (GSH) without ROS overproduction and intracellular Ca2+
      influx. Co-incubation of both bioactive compounds protected against beta-Cx
      induced eryptosis. Under tBOOH stress, PS prevented eryptosis, reducing Ca2+
      influx, ROS overproduction and GSH depletion at 75 MUM, and hemolysis at both
      tBOOH concentrations. beta-Cryptoxanthin showed no cytoprotective effect. Co
      incubation with both bioactive compounds completely prevented hemolysis and
      partially prevented eryptosis as well as GSH depletion induced by beta-Cx plus
      tBOOH. Phytosterols at physiological serum concentrations help to prevent pro
      eryptotic and hemolytic effects and are promising candidate compounds for
      ameliorating eryptosis-associated diseases.

PMID- 29345908
TI  - A Small-Molecule Inhibitor of Human DNA Polymerase eta Potentiates the Effects of
      Cisplatin in Tumor Cells.
AB  - Translesion DNA synthesis (TLS) performed by human DNA polymerase eta (hpol eta)
      allows tolerance of damage from cis-diamminedichloroplatinum(II) (CDDP or
      cisplatin). We have developed hpol eta inhibitors derived from N-aryl-substituted
      indole barbituric acid (IBA), indole thiobarbituric acid (ITBA), and indole
      quinuclidine scaffolds and identified 5-((5-chloro-1-(naphthalen-2-ylmethyl)-1H
      indol-3-yl)methylene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione (PNR-7-02), an
      ITBA derivative that inhibited hpol eta activity with an IC50 value of 8 MUM and
      exhibited 5-10-fold specificity for hpol eta over replicative pols. We conclude
      from kinetic analyses, chemical footprinting assays, and molecular docking that
      PNR-7-02 binds to a site on the little finger domain and interferes with the
      proper orientation of template DNA to inhibit hpol eta. A synergistic increase in
      CDDP toxicity was observed in hpol eta-proficient cells co-treated with PNR-7-02
      (combination index values = 0.4-0.6). Increased gammaH2AX formation accompanied
      treatment of hpol eta-proficient cells with CDDP and PNR-7-02. Importantly, PNR-7
      02 did not impact the effect of CDDP on cell viability or gammaH2AX in hpol eta
      deficient cells. In summary, we observed hpol eta-dependent effects on DNA
      damage/replication stress and sensitivity to CDDP in cells treated with PNR-7-02.
      The ability to employ a small-molecule inhibitor of hpol eta to improve the
      cytotoxic effect of CDDP may aid in the development of more effective
      chemotherapeutic strategies.

PMID- 29345909
TI  - Metabolomics Study Reveals Enhanced Inhibition and Metabolic Dysregulation in
      Escherichia coli Induced by Lactobacillus acidophilus-Fermented Black Tea
      Extract.
AB  - This study examined the ability of Lactobacillus acidophilus (LA) to ferment
      black tea extract (BTE) and the enhancement of Escherichia coli cellular uptake
      of phenolic compounds when these bacteria were incubated with fermented BTE. The
      inhibitory effects of BTE to E. coli bacteria with and without fermentation were
      compared. Several intracellular phenolic compounds as well as metabolic profiles
      of E. coli with and without treatments were also determined using a high
      performance liquid chromatography-tandem mass spectrometry-based approach. Our
      results showed that of three concentrations from the non-fermented BTE treatment,
      only the extract from the 25 mg/mL tea leaves solution could inhibit E. coli
      survival, while LA-fermented BTE extract from 5, 10, and 25 mg/mL tea leaves
      solutions all inhibited E. coli growth significantly. Intracellular
      concentrations of (+)-catechin-3-gallate/(-)-epicatechin-3-gallate and (+)
      catechin/(-)-epicatechin were significantly higher when E. coli was treated with
      fermented BTE in comparison to non-fermented BTE. Scanning electron microscopy
      images indicated that the intracellular phenolic compounds inhibited E. coli
      growth by increasing endogenous oxidative stress. Metabolic profiles of E. coli
      were also investigated to understand their metabolic response when treated with
      BTE, and significant metabolic changes of E. coli were observed. Metabolic
      profile data were further analyzed using partial least squares discriminant
      analysis to distinguish the fermented BTE treatment group from the control group
      and the non-fermented BTE treatment group. The results indicated a large-scale E.
      coli metabolic dysregulation induced by the fermented BTE. Our findings showed
      that LA fermentation can be an efficient approach to enhance phenolic inhibition
      of bacterial cells through increased endogenous oxidative stress and dysregulated
      metabolic activities.

PMID- 29345910
TI  - Qualitative and Quantitative Analysis of Ethanolic Extract and Phenolic Fraction
      of Jatropha aethiopica (Euphorbiaceae) Leaves and Their Hypoglycemic Potential.
AB  - Although Jatropha aethiopica, popularly known in Cuba as "mata diabetes", is used
      in salads and as a dietary supplement, its chemical composition and antidiabetic
      properties yet remains unclear. In this work, we evaluate the qualitative and
      quantitative composition of ethanolic extract (EE) and phenolic fraction (PF) of
      Jatropha aethiopica leaves and their hypoglycemic and hypolipidemic activity.
      Chemical fractionation of the ethanolic extract yielded nine compounds, which
      included protocatechuic acid (1), chlorogenic acid (2), caffeic acid (3),
      quercetin 3-O-alpha-l-rhamnopyranosyl-(1 -> 2)-[alpha-l-rhamnopyranolsyl-(1 ->
      6)]-beta-d-galactopyranoside (4), a new kaempferol 3-O-alpha-l-rhamnopyranosyl-(1
      -> 4)-[alpha-l-rhamnopyranolsyl-(1 -> 6)]-beta-d-galactopyranoside (5),
      kaempferol 3-O-alpha-l-rhamnopyranosyl-(1 -> 2)-[alpha-l-rhamnopyranolsyl-(1 ->
      6)]-beta-d-glucopyranoside (6), rutin (7), kaempferol 3-O-alpha-l-rhamnopyranosyl
      (1 -> 6)-beta-d-glucopyranoside (8), and quercetin (9). The compounds (1, 4-7)
      were quantified by high-performance liquid chromatography photodiode array
      detection (HPLC-PDA) in both the ethanolic extract (62.65 +/- 0.15 mg/g) and
      phenolic fraction (61.72 +/- 0.23 mg/g). The results obtained show that both
      ethanolic extract and phenolic fraction contributed toward the improvement of
      glucose tolerance, which in turn led to a decline in the glucose levels.
      Remarkably, the ethanolic extract presented a relatively higher promising effect
      compared to metformin.

PMID- 29345911
TI  - Role of Glycanation and Convertase Maturation of Soluble Glypican-3 in Inhibiting
      Proliferation of Hepatocellular Carcinoma Cells.
AB  - Glypican 3 (GPC3) is a complex heparan sulfate proteoglycan associated with the
      outer surface of the plasma membrane by a glycosylphosphatidylinositol (GPI)
      anchor. It is also N-glycosylated and processed by a furin-like convertase. GPC3
      has numerous biological functions. Although GPC3 is undetectable in normal liver
      tissue, it is abnormally and highly overexpressed in hepatocellular carcinoma
      (HCC). Interestingly, proliferation of HCC cells such as HepG2 and HuH7 is
      inhibited when they express a soluble form of GPC3 after lentiviral transduction.
      To obtain more insight into the role of some of its post-translational
      modifications, we designed a mutant GPC3, sGPC3m, without its GPI anchor,
      convertase cleavage site, and glycosaminoglycan chains. The highly pure sGPC3m
      protein strongly inhibited HuH7 and HepG2 cell proliferation in vitro and induced
      a significant increase in their cell doubling time. It changed the morphology of
      HuH7 cells but not that of HepG2. It induced the enlargement of HuH7 cell nuclear
      area and the restructuration of adherent cell junctions. Unexpectedly, for both
      cell types, the levels of apoptosis, cell division, and beta-catenin were not
      altered by sGPC3m, although growth inhibition was very efficient. Overall, our
      data show that glycanation and convertase maturation are not required for sGPC3m
      to inhibit HCC cell proliferation.

PMID- 29345912
TI  - A (Re)Discovery of the Fom3 Substrate.

PMID- 29345913
TI  - Non-Centrosymmetric RbNaMgP2O7 with Unprecedented Thermo-Induced Enhancement of
      Second Harmonic Generation.
AB  - It is of great difficulty to obtain deep-UV transparent materials with enhanced
      second harmonic generation (SHG), mainly limited by the theoretically poor
      transparency of these materials in the deep-UV spectral region. Here we report a
      new noncentrosymmetric, deep-UV transparent phosphate RbNaMgP2O7, which undergoes
      a thermo-induced reversible phase transition (at a high temperature of 723 K) and
      correspondingly an evident SHG enhancement up to ~1.5 times. The phase transition
      is aroused by the twist of [P2O7]4- dimers with deviation from the P-O-P
      equilibrium positions. Theoretical analyses reveal that the enhanced SHG can be
      ascribed to the thermo-induced collective alignment of SHG-active [P2O7]4- dimers
      along the polar axis of high-temperature phase. This work provides an
      unprecedented physical routine (to SHG-enhanced materials) that is distinguished
      from the traditional one by chemical design and synthesis.

PMID- 29345914
TI  - Comparative Analysis of EPA/DHA-PL Forage and Liposomes in Orotic Acid-Induced
      Nonalcoholic Fatty Liver Rats and Their Related Mechanisms.
AB  - Nonalcoholic fatty liver disease (NAFLD) has become one predictive factor of
      death from various illnesses. The present study was to comparatively investigate
      the effects of eicosapentaenoic acid-enriched and docosahexaenoic acid-enriched
      phospholipids forage (EPA-PL and DHA-PL) and liposomes (lipo-EPA and lipo-DHA) on
      NAFLD and demonstrate the possible protective mechanisms involved. The additive
      doses of EPA-PL and DHA-PL in all treatment groups were 1% of total diets,
      respectively. The results showed that Lipo-EPA could significantly improve
      hepatic function by down-regulating orotic acid-induced serum aspartate
      aminotransferase (AST) and alanine aminotransferase (ALT) levels by 55.6% and
      34.2%, respectively (p < 0.01). Moreover, lipo-EPA exhibited excellent inhibition
      on the mRNA expression of SREBP-1c and FAS at the values of 0.454 +/- 0.09 (p <
      0.01) and 0.523 +/- 0.08 (p < 0.01), respectively, thus ameliorating OA-induced
      NAFLD. Meanwhile, lipo-EPA could significantly suppress the SREBP-2 and HMGR
      levels (31.4% and 66.7%, p < 0.05, respectively). In addition, EPA-PL and lipo
      DHA could also significantly suppress hepatic lipid accumulation mainly by
      enhancement of hepatic lipolysis and cholesterol efflux. Furthermore, DHA-PL
      played a certain role in inhibiting hepatic lipogenesis and accelerating
      cholesterol efflux. The results obtained in this work might contribute to the
      understanding of the biological activities of EPA/DHA-PL and liposomes and
      further investigation on its potential application values for food supplements.

PMID- 29345915
TI  - The Effect of Water on Quinone Redox Mediators in Nonaqueous Li-O2 Batteries.
AB  - The parasitic reactions associated with reduced oxygen species and the difficulty
      in achieving the high theoretical capacity have been major issues plaguing
      development of practical nonaqueous Li-O2 batteries. We hereby address the above
      issues by exploring the synergistic effect of 2,5-di-tert-butyl-1,4-benzoquinone
      and H2O on the oxygen chemistry in a nonaqueous Li-O2 battery. Water stabilizes
      the quinone monoanion and dianion, shifting the reduction potentials of the
      quinone and monoanion to more positive values (vs Li/Li+). When water and the
      quinone are used together in a (largely) nonaqueous Li-O2 battery, the cell
      discharge operates via a two-electron oxygen reduction reaction to form Li2O2,
      with the battery discharge voltage, rate, and capacity all being considerably
      increased and fewer side reactions being detected. Li2O2 crystals can grow up to
      30 MUm, more than an order of magnitude larger than cases with the quinone alone
      or without any additives, suggesting that water is essential to promoting a
      solution dominated process with the quinone on discharging. The catalytic
      reduction of O2 by the quinone monoanion is predominantly responsible for the
      attractive features mentioned above. Water stabilizes the quinone monoanion via
      hydrogen-bond formation and by coordination of the Li+ ions, and it also helps
      increase the solvation, concentration, lifetime, and diffusion length of reduced
      oxygen species that dictate the discharge voltage, rate, and capacity of the
      battery. When a redox mediator is also used to aid the charging process, a high
      power, high energy density, rechargeable Li-O2 battery is obtained.

PMID- 29345916
TI  - Monitoring H2O2 inside Aspergillus fumigatus with an Integrated Microelectrode:
      The Role of Peroxiredoxin Protein Prx1.
AB  - Peroxiredoxins (Prx) are important proteins involved in hydroperoxide degradation
      and are related to virulence in several pathogens, including Aspergillus
      fumigatus. In this work, in vivo studies on the degradation of hydrogen peroxide
      (H2O2) in the microenvironment of A. fumigatus fungus were performed by using an
      integrated Pt microelectrode. Three A. fumigatus strains were used to confirm the
      role of the cytosolic protein Prx1 in the defense mechanism of this
      microorganism: a wild-type strain, capable to expressing the protein Prx1; a
      Deltaprx strain, whose gene prx1 was removed; and a genetically complemented
      Deltaprx1::prx1+ strain generated from the Deltaprx1 and in which the gene prx1
      was reintroduced. The fabricated microelectrode was shown to be a reliable inert
      probe tip for in situ and real-time measurements of H2O2 in such
      microenvironments, with potential applications in investigations involving the
      mechanism of oxidative stress.

PMID- 29345917
TI  - Anisotropic Assembly of Ag52 and Ag76 Nanoclusters.
AB  - Although there has been an upsurge of interest in anisotropic assembly of
      inorganic nanoparticles, atomically precise self-assembly of anisotropic metal
      clusters is extremely rare. Herein, we presented two novel silver nanoclusters,
      Ag52 (SD/Ag23) and Ag76 (SD/Ag24), which are interiorly templated by five MoO42-
      and a pair of Mo6O228- anions, respectively, and coprotected by bridging RSH and
      terminal diphosphine ligands exteriorly. Regiospecific distribution diphosphine
      ligands on the surface and the arrangement of multiple molybdate templates within
      the nanoclusters synergetically tailor their shapes to anisotropic oblate
      spheroid and elongated rod, respectively. This work not only open up new avenues
      for the synthesis of silver nanoclusters with novel metal skeleton shapes and
      anisotropic surface structures but also give important insights for the
      anisotropic growth of silver nanoclusters through surface modifications or/and
      template organizations.

PMID- 29345918
TI  - Anti-Inflammatory and Antioxidant Activities from the Basolateral Fraction of
      Caco-2 Cells Exposed to a Rosmarinic Acid Enriched Extract.
AB  - The potential use of Origanum majorana L. as a source of bioavailable phenolic
      compounds, specifically rosmarinic acid (RA), has been evaluated. Phenolic
      bioavailability was tested using an in vitro digestion process followed by a Caco
      2 cellular model of intestinal absorption. The high-performance liquid
      chromatography-photodiode array detector-tandem mass spectrometry (HPLC-PAD
      MS/MS) analysis showed the main components in the extract were 6-hydroxyluteolin
      7-O-glucoside and rosmarinic acid, followed by luteolin-O-glucoside. After
      digestion process, the amount of total phenolic compounds (TPC) only decreased
      slightly, although a remarkable reduction in RA (near 50%) was detected.
      Bioavailable fraction contained 7.37 +/- 1.39 mg/L digested extract of RA with
      small quantities of lithospermic acid and diosmin and presented an important
      antioxidant activity (0.89 +/- 0.09 mmol Trolox/L digested extract). Besides,
      this bioavailable fraction produced a significant inhibition in TNF-alpha, IL
      1beta, and IL-6 secretion, using a human THP-1 macrophages model. Therefore, RA
      content in the basolateral compartment could play an important role in the
      antioxidant and anti-inflammatory activities found.

PMID- 29345919
TI  - Using Isomeric and Metabolic Ratios of DDT To Identify the Sources and Fate of
      DDT in Chinese Agricultural Topsoil.
AB  - The metabolic ratio of (p,p'-DDE + p,p'-DDD)/p,p'-DDT or p,p'-DDE/p,p'-DDT has
      been used previously to estimate the approximate half-life of p,p'-DDT, with a
      relatively unclear concept of "old" and "new" sources of p,p'-DDT and without
      paying attention to the influence by dicofol-type DDT contributed from the more
      recent usage of dicofol. Based on the isomeric ratio of o,p'-DDT/p,p'-DDT to
      distinguish the sources of DDT, this study used the corrected metabolic ratio of
      (p,p'-DDE + p,p'-DDD)/p,p'-DDT to estimate a more accurate half-life of p,p'-DDT
      using a model-based approach. This indicates the average half-life of p,p'-DDT in
      Chinese topsoils was 14.2 +/- 0.9 years with dicofol-type DDT input considered.
      In deeper soil, the half-life was >30 years and the metabolic pathway of p,p'-DDT
      was significantly different with topsoil's. Further analysis on the fraction of
      DDT from technical DDT suggested that a region that had been sprayed with
      technical DDT was likely to have been sprayed with dicofol as well, but the
      monitoring residues of DDT in topsoil mainly derive from historical use of
      technical DDT.

PMID- 29345921
TI  - Molecular Mechanisms in the Selectivity of Nonsteroidal Anti-Inflammatory Drugs.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase (COX) 1 and
      2 with varying degrees of selectivity. A group of COX-2 selective inhibitors
      coxibs-binds in a time-dependent manner through a three-step mechanism, utilizing
      a side pocket in the binding site. Coxibs have been extensively probed to
      identify the structural features regulating the slow tight-binding mechanism
      responsible for COX-2 selectivity. In this study, we further probe a structurally
      and kinetically diverse data set of COX inhibitors in COX-2 by molecular dynamics
      and free energy simulations. We find that the features regulating the high
      affinities associated with time-dependency in COX depend on the inhibitor
      kinetics. In particular, most time-dependent inhibitors share a common structural
      binding mechanism, involving an induced-fit rotation of the side-chain of Leu531
      in the main binding pocket. The high affinities of two-step slow tight-binding
      inhibitors and some slow reversible inhibitors can thus be explained by the
      increased space in the main binding pocket after this rotation. Coxibs that
      belong to a separate class of slow tight-binding inhibitors benefit more from the
      displacement of the neighboring side-chain of Arg513, exclusive to the COX-2 side
      pocket. This displacement further stabilizes the aforementioned rotation of
      Leu531 and can explain the selectivity of coxibs for COX-2.

PMID- 29345920
TI  - Acetylation by Eis and Deacetylation by Rv1151c of Mycobacterium tuberculosis
      HupB: Biochemical and Structural Insight.
AB  - Bacterial nucleoid-associated proteins (NAPs) are critical to genome integrity
      and chromosome maintenance. Post-translational modifications of bacterial NAPs
      appear to function similarly to their better studied mammalian counterparts. The
      histone-like NAP HupB from Mycobacterium tuberculosis (Mtb) was previously
      observed to be acetylated by the acetyltransferase Eis, leading to genome
      reorganization. We report biochemical and structural aspects of acetylation of
      HupB by Eis. We also found that the SirT-family NAD+-dependent deacetylase
      Rv1151c from Mtb deacetylated HupB in vitro and characterized the deacetylation
      kinetics. We propose that activities of Eis and Rv1151c could regulate the
      acetylation status of HupB to remodel the mycobacterial chromosome in response to
      environmental changes.

PMID- 29345923
TI  - Capped Polyoxometalate Pillars between Metal-Organic Layers for Transferring a
      Supramolecular Structure into a Covalent 3D Framework.
AB  - Two robust metal-organic frameworks (MOFs), {H4[Ni(pi-H2O)2]2[Ni(rt
      H2O)2]8Ni4(Tri)24}[VIVW12O40]2.24H2O (1) and {H[Ni(pi-O)2]2[Ni(rt
      H2O)2]8Ni4(Tri)24}[VIVW10VV2O40V2][VIVW9VV3O40VIV2].24H2O (2) (Tri = 1,2,4
      triazole), composed of polyoxometalates (POMs) and metal-organic units, were
      designed and synthesized by a hydrothermal method. Structure analysis indicates
      that there is a metal-organic crown [{Ni3(Tri)6(H2O)4}4] ({Ni12}) in these two
      compounds. In 1, the {Ni12} crown embraces four pendant Tri ligands that could
      capture a cationic [Ni(H2O)2]2+ group, resulting in the Ni13-Tri building unit
      [Ni(H2O)2{Ni3(Tri)6(H2O)4}4] ({Ni13}). The {Ni13} building unit was fused
      together by Tri bridges into the 2D metal-organic layers, which are pillared by a
      typical Keggin-type POM [VW12O40]4- to construct a 3D supramolecular framework
      via the hydrogen bonds. Interestingly, the 2D metal-organic layer in 1 was
      successfully transferred into a 3D covalent MOF via extension of the length of
      the pillars by capping a Keggin-type POM with V-O units. Moreover,
      electrochemical behaviors and electrocatalytic properties of these two compounds
      were both studied, which can act as bifunctional electrocatalysts toward the
      reduction of H2O2 and oxidation of nitrite in neutral aqueous solution.

PMID- 29345924
TI  - Domain-Based Local Pair Natural Orbital Version of Mukherjee's State-Specific
      Coupled Cluster Method.
AB  - This article reports development of a local variant of Mukherjee's state-specific
      multireference coupled cluster method based on the domain-based pair natural
      orbital approach (DLPNO-MkCC). The current implementation is restricted to
      connected single and double excitations and model space with up to biexcited
      references. The performance of the DLPNO-MkCCSD was tested on calculations of
      tetramethyleneethane. The results show that above 99.9% of the correlation energy
      was recovered, with respect to the conventional MkCC method. To demonstrate the
      applicability of the method to large systems, singlet-triplet gaps of triangulene
      and bis(1-(2,6-diisopropylphenyl)-3,3,5,5-tetramethylpyrrolidine-2
      ylidene)beryllium complex were studied. For the last system (105 atoms), we were
      able to perform a calculation in cc-pVTZ with 2158 basis functions on a single
      CPU in less than 9 days.

PMID- 29345922
TI  - Efficient Fusion at Neutral pH by Human Immunodeficiency Virus gp41 Trimers
      Containing the Fusion Peptide and Transmembrane Domains.
AB  - Human immunodeficiency virus (HIV) is membrane-enveloped, and an initial
      infection step is joining/fusion of viral and cell membranes. This step is
      catalyzed by gp41, which is a single-pass integral viral membrane protein. The
      protein contains an ~170-residue ectodomain located outside the virus that is
      important for fusion and includes the fusion peptide (FP), N-helix, loop, C
      helix, and viral membrane-proximal external region (MPER). The virion initially
      has noncovalent complexes between three gp41 ectodomains and three gp120
      proteins. A gp120 contains ~500 residues and functions to identify target T-cells
      and macrophages via binding to specific protein receptors of the target cell
      membrane. gp120 moves away from the gp41 ectodomain, and the ectodomain is
      thought to bind to the target cell membrane and mediate membrane fusion. The
      secondary and tertiary structures of the ectodomain are different in the initial
      complex with gp120 and the final state without gp120. There is not yet imaging of
      gp41 during fusion, so the temporal relationship between the gp41 and membrane
      structures is not known. This study describes biophysical and functional
      characterization of large gp41 constructs that include the ectodomain and
      transmembrane domain (TM). Significant fusion is observed of both neutral and
      anionic vesicles at neutral pH, which reflects the expected conditions of
      HIV/cell fusion. Fusion is enhanced by the FP, which in HIV/cell fusion likely
      contacts the host membrane, and the MPER and TM, which respectively interfacially
      contact and traverse the HIV membrane. Initial contact with vesicles is made by
      protein trimers that are in a native oligomeric state that reflects the initial
      complex with gp120 and also is commonly observed for the ectodomain without
      gp120. Circular dichroism data support helical structure for the N-helix, C
      helix, and MPER and nonhelical structure for the FP and loop. Distributions of
      monomer, trimer, and hexamer states are observed by size-exclusion chromatography
      (SEC), with dependences on solubilizing detergent and construct. These SEC and
      other data are integrated into a refined working model of HIV/cell fusion that
      includes dissociation of the ectodomain into gp41 monomers followed by folding
      into hairpins that appose the two membranes, and subsequent fusion catalysis by
      trimers and hexamers of hairpins. The monomer and oligomer gp41 states may
      therefore satisfy dual requirements for HIV entry of membrane apposition and
      fusion.

PMID- 29345925
TI  - Catalytic Mechanism of the Ubiquitin-Like NEDD8 Transfer in RING E3-E2~NEDD8
      Target Complex from QM/MM Free Energy Simulations.
AB  - Ubiquitin-like (UBL) protein modifications play a key role in regulating protein
      function. In contrast to the ubiquitin (UB) and small ubiquitin-like modifier
      (SUMO) which are ligated to a massive segment of proteome, the UBL NEDD8 is
      highly selective for modifying a lysine residue on closely related cullin
      proteins (CULs). In this study, the X-ray structure of a trapped E3-E2~NEDD8
      target intermediate (RBX1-UBC1~NEDD8-CUL1-DCN1) is used to build computer models,
      and combined quantum mechanics/molecular mechanics (QM/MM) molecular dynamics
      (MD) and free energy (potential of mean force) simulations are performed to
      investigate the catalytic mechanism of the NEDD8 transfer from E2 to the lysine
      residue (K720) on the substrate in the complex. The role of the active site
      residues is examined. The simulation results show that either E117 or D143 from
      E2 may be able to work as a general base catalyst to deprotonate K720 on the
      substrate, and K720 can then perform the nucleophilic attack on the thioester
      bond linking E2 and NEDD8. It is also shown that the formation of a new
      isopeptide bond between K720 and NEDD8 and the breaking of the thioester bond are
      concerted based on the computer simulations. Furthermore, the results suggest
      that K720 may act as a general acid catalyst to protonate the leaving group of
      C111 from E2. The free energy barrier for nucleophilic attack is estimated to be
      14-15 kcal/mol based on the free energy simulations.

PMID- 29345926
TI  - Investigation on the Thermodynamic Dissociation Kinetics of Photosystem II
      Supercomplexes To Determine the Binding Strengths of Light-Harvesting Complexes.
AB  - The photosystem II (PSII) supercomplex splits water utilizing light energy and is
      composed of a core dimer complex surrounded by light-harvesting complexes (LHCs).
      In green algae, the major LHCs which are LHCII trimers have thus far been
      categorized into strongly, moderately, or loosely binding LHCII trimers based on
      their predicted binding to core complexes. However, the binding energies have
      been indirectly predicted based on the presence or absence of LHCII trimers in
      the PSII supercomplex under electron microscopy and have not been determined
      experimentally. In this study, we investigated the binding of LHCII trimers by
      analyzing thermodynamic dissociation kinetics using isolated PSII supercomplexes.
      We identified two activation energies for dissociation of LHCII trimers: 54 +/-
      19 and 134 +/- 8 kJ/mol. This result indicated the types of intermolecular
      interactions between LHCII trimers and core complexes.

PMID- 29345927
TI  - Embedded Multireference Coupled Cluster Theory.
AB  - Internally contracted multireference coupled cluster (icMRCC) theory is embedded
      within multireference perturbation theory (MRPT) to calculate energy differences
      in large strongly correlated systems. The embedding scheme is based on
      partitioning the orbital spaces of a complete active space self-consistent field
      (CASSCF) wave function, with a truncated virtual space constructed by
      transforming selected projected atomic orbitals (PAOs). MRPT is applied to the
      environment using a subtractive embedding approach that also allows for
      multilayer embedding. Benchmark calculations are presented for biradical bond
      dissociation, spin splitting in a heterocyclic carbene and hydrated Fe(II), and
      for the super-exchange coupling constant in solid nickel oxide. The method is
      further applied to two large transition metal complexes with a triple-zeta basis
      set: an iron complex with 175 atoms and 2939 basis functions, and a nickel
      complex with 231 atoms, and 4175 basis functions.

PMID- 29345928
TI  - Physicochemical Properties of Whey-Protein-Stabilized Astaxanthin Nanodispersion
      and Its Transport via a Caco-2 Monolayer.
AB  - Astaxanthin nanodispersion was prepared using whey protein isolate (WPI) and
      polymerized whey protein (PWP) through an emulsification-evaporation technique.
      The physicochemical properties of the astaxanthin nanodispersion were evaluated,
      and the transport of astaxanthin was assessed using a Caco-2 cell monolayer
      model. The astaxanthin nanodispersions stabilized by WPI and PWP (2.5%, w/w) had
      a small particle size (121 +/- 4.9 and 80.4 +/- 5.9 nm, respectively), negative
      zeta potential (-19.3 +/- 1.5 and -35.0 +/- 2.2 mV, respectively), and high
      encapsulation efficiency (92.1 +/- 2.9 and 93.5 +/- 2.4%, respectively).
      Differential scanning calorimetry curves indicated that amorphous astaxanthin
      existed in both astaxanthin nanodispersions. Whey-protein-stabilized astaxanthin
      nanodispersion showed resistance to pepsin digestion but readily released
      astaxanthin after trypsin digestion. The nanodispersions showed no cytotoxicity
      to Caco-2 cells at a protein concentration below 10 mg/mL. WPI- and PWP
      stabilized nanodispersions improved the apparent permeability coefficient (Papp)
      of Caco-2 cells to astaxanthin by 10.3- and 16.1-fold, respectively. The results
      indicated that whey-protein-stabilized nanodispersion is a good vehicle to
      deliver lipophilic bioactive compounds, such as astaxanthin, and to improve their
      bioavailability.

PMID- 29345929
TI  - Antihypertensive Effects, Molecular Docking Study, and Isothermal Titration
      Calorimetry Assay of Angiotensin I-Converting Enzyme Inhibitory Peptides from
      Chlorella vulgaris.
AB  - The aim of this work is to explore angiotensin I-converting enzyme (ACE)
      inhibitory peptides from Chlorella vulgaris (C. vulgaris) and discover the
      inhibitory mechanism of the peptides. After C. vulgaris proteins were
      gastrointestinal digested in silico, several ACE inhibitory peptides with C
      terminal tryptophan were screened. Among them, two novel noncompetitive ACE
      inhibitors, Thr-Thr-Trp (TTW) and Val-His-Trp (VHW), exhibited the highest
      inhibitory activity indicated by IC50 values 0.61 +/- 0.12 and 0.91 +/- 0.31 MUM,
      respectively. Both the peptides were demonstrated stable against gastrointestinal
      digestion and ACE hydrolysis. The peptides were administrated to spontaneously
      hypertensive rats (SHRs) in the dose 5 mg/kg body weight, and VHW could decrease
      50 mmHg systolic blood pressure of SHRs (p < 0.05). Molecular docking displayed
      that both TTW and VHW formed six hydrogen bonds with active site pockets of ACE.
      Besides, isothermal titration calorimetry assay discovered that VHW could form
      more stable complex with ACE than TTW. Therefore, VHW was an excellent ACE
      inhibitor.

PMID- 29345930
TI  - alpha-Amino-beta-carboxymuconate-epsilon-semialdehyde Decarboxylase (ACMSD)
      Inhibitors as Novel Modulators of De Novo Nicotinamide Adenine Dinucleotide
      (NAD+) Biosynthesis.
AB  - NAD+ has a central function in linking cellular metabolism to major cell
      signaling and gene-regulation pathways. Defects in NAD+ homeostasis underpin a
      wide range of diseases, including cancer, metabolic disorders, and aging.
      Although the beneficial effects of boosting NAD+ on mitochondrial fitness,
      metabolism, and lifespan are well established, to date, no therapeutic enhancers
      of de novo NAD+ biosynthesis have been reported. Herein we report the discovery
      of 3-[[[5-cyano-1,6-dihydro-6-oxo-4-(2-thienyl)-2
      pyrimidinyl]thio]methyl]phenylacetic acid (TES-1025, 22), the first potent and
      selective inhibitor of human ACMSD (IC50 = 0.013 MUM) that increases NAD+ levels
      in cellular systems. The results of physicochemical-property, ADME, and safety
      profiling, coupled with in vivo target-engagement studies, support the hypothesis
      that ACMSD inhibition increases de novo NAD+ biosynthesis and position 22 as a
      first-class molecule for the evaluation of the therapeutic potential of ACMSD
      inhibition in treating disorders with perturbed NAD+ supply or homeostasis.

PMID- 29345931
TI  - Umbrella Sampling and X-ray Crystallographic Analysis Unveil an Arg-Asp Gate
      Facilitating Inhibitor Binding Inside Phosphopantetheine Adenylyltransferase
      Allosteric Cleft.
AB  - Phosphopantetheine adenylyltransferase (PPAT) is a rate-limiting enzyme essential
      for biosynthesis of coenzyme A (CoA), which in turn is responsible to regulate
      the secretion of exotoxins via type III secretion system in Pseudomonas
      aeruginosa, causing severe health concerns ranging from nosocomial infections to
      respiratory failure. Acetyl coenzyme A (AcCoA) is a newly reported inhibitor of
      PPAT, believed to regulate the cellular levels of CoA and thereby the
      pathogenesis. Very little is known so far regarding the mechanistic details of
      AcCoA binding inside PPAT-binding cleft. Herein, we have used extensive umbrella
      sampling simulations to decipher mechanistic insight into the inhibitor
      accommodation inside the binding cavity. We found that R90 and D94 residues act
      like a gate near the binding cavity to accommodate and stabilize the incoming
      ligand. Mutational models concerning these residues also show considerable
      difference in AcCoA-binding thermodynamics. To substantiate our findings, we have
      solved the first crystal structure of apo-PPAT from P. aeruginosa, which also
      found to agree with the simulation results. Collectively, these results describe
      the mechanistic details of accommodation of inhibitor molecule inside PPAT
      binding cavity and also offer valuable insight into regulating cellular levels of
      CoA/AcCoA and thus controlling the pathogenicity.

PMID- 29345932
TI  - Synthesis of Polysubstituted Quinolines from alpha-2-Aminoaryl Alcohols Via
      Nickel-Catalyzed Dehydrogenative Coupling.
AB  - This study reports a nickel-catalyzed sustainable synthesis of polysubstituted
      quinolines from alpha-2-aminoaryl alcohols by a sequential dehydrogenation and
      condensation process that offers the advantages of a low catalyst loading and
      wide substrate scope. In contrast to earlier reported methods, this strategy
      allows the use of both primary as well as secondary alpha-2-aminoaryl alcohols in
      combination with either ketones or secondary alcohols for desired product
      formation. Using this methodology, 30 substituted quinoline derivatives were
      synthesized with up to 93% isolated yields.

PMID- 29345933
TI  - Large-Scale Functional Group Symmetry-Adapted Perturbation Theory on Graphical
      Processing Units.
AB  - Symmetry-adapted perturbation theory (SAPT) is a valuable method for analyzing
      intermolecular interactions. The functional group SAPT partition (F-SAPT) has
      been introduced to provide additional insight into the origins of noncovalent
      interactions. Until now, SAPT analysis has been too costly for large ligand
      protein complexes where it could provide key insights for chemical modifications
      that might improve ligand binding. In this paper, we present a large-scale
      implementation of a variant of F-SAPT. Two pragmatic choices are made from the
      outset to render the problem tractable: (1) Ab initio computation of dispersion
      and exchange-dispersion is replaced with Grimme's empirical dispersion
      correction. (2) Basis sets with augmented functions are avoided to allow for
      efficient integral screening. These choices allow the F-SAPT analysis to be
      written largely in terms of Coulomb and exchange matrix builds which have been
      implemented efficiently on graphical processing units (GPUs). Our formulation of
      F-SAPT is routinely applicable to molecules with well over 3000 atoms and 25,000
      basis functions and is particularly optimized for the case where one monomer is
      significantly larger than the other. This is demonstrated explicitly with results
      from F-SAPT analysis of the full indinavir @ HIV-II protease complex (PDB ID 1HSG
      ) in a polarized double-zeta basis.

PMID- 29345934
TI  - Zein Nanoparticles as Eco-Friendly Carrier Systems for Botanical Repellents
      Aiming Sustainable Agriculture.
AB  - Botanical repellents represent one of the main ways of reducing the use of
      synthetic pesticides and the contamination of soil and hydric resources. However,
      the poor stability and rapid degradation of these compounds in the environment
      hinder their effective application in the field. Zein nanoparticles can be used
      as eco-friendly carrier systems to protect these substances against premature
      degradation, provide desirable release characteristics, and reduce toxicity in
      the environment and to humans. In this study, we describe the preparation and
      characterization of zein nanoparticles loaded with the main constituents of the
      essential oil of citronella (geraniol and R-citronellal). The phytotoxicity,
      cytotoxicity, and insect activity of the nanoparticles toward target and
      nontarget organisms were also evaluated. The botanical formulations showed high
      encapsulation efficiency (>90%) in the nanoparticles, good physicochemical
      stability, and effective protection of the repellents against UV degradation.
      Cytotoxicity and phytotoxicity assays showed that encapsulation of the botanical
      repellents decreased their toxicity. Repellent activity tests showed that
      nanoparticles containing the botanical repellents were highly repellent against
      the Tetranychus urticae Koch mite. This nanotechnological formulation offers a
      new option for the effective use of botanical repellents in agriculture, reducing
      toxicity, protecting against premature degradation, and providing effective pest
      control.

PMID- 29345935
TI  - Rhodium-Catalyzed Asymmetric [2 + 2 + 2] Cycloaddition of Unsymmetrical
      alpha,omega-Diynes with Acenaphthylene.
AB  - It has been established that a cationic rhodium(I)/(R)-BINAP complex catalyzes
      the asymmetric [2 + 2 + 2] cycloaddition of unsymmetrical alpha,omega-diynes with
      acenaphthylene at room temperature to give the corresponding chiral multicyclic
      compounds with high yields and ee values. Interestingly, enantioselectivity
      highly depended on the structures of alpha,omega-diynes used. The structural
      requirements of alpha,omega-diynes for high enantioselectivity were opposite to
      those in our previously reported cationic rhodium(I)/(R)-Difluorphos complex
      catalyzed asymmetric [2 + 2 + 2] cycloaddition of alpha,omega-diynes with indene.

PMID- 29345936
TI  - Copper-Catalyzed One-Pot Cross-Dehydrogenative Thienannulation: Chemoselective
      Access to Naphtho[2,1-b]thiophene-4,5-diones and Subsequent Transformation to
      Benzo[a]thieno[3,2-c]phenazines.
AB  - A facile, cost-effective, and highly efficient copper-catalyzed, TEMPO-mediated
      straightforward synthesis of 2,3-disubstituted naphtho[2,1-b]thiophene-4,5-diones
      has been achieved via cross-dehydrogenative thienannulation. The reaction
      proceeded via in situ generated naphthalene-1,2-diones by dearomatization of beta
      naphthols, followed by oxidative heteroannulation with alpha-enolic dithioesters
      chemoselectively in an open flask. Further, the naphtho[2,1-b]thiophene-4,5
      diones undergo l-proline-catalyzed cross-dehydrative coupling with ortho
      phenylenediamine enabling pentacyclic benzo[a]thieno[3,2-c]phenazines in good
      yields under solvent-free conditions. A mechanistic rationale for this cascade
      reaction sequence is well supported by the control experiments.

PMID- 29345937
TI  - Hole Hopping Rates in Organic Semiconductors: A Second-Order Cumulant Approach.
AB  - Second-order cumulant expansion of the time dependent reduced density matrix has
      been employed to evaluate hole hopping rates in pentacene, tetracene, picene, and
      rubrene homodimers. The cumulant expansion is a full quantum mechanical approach,
      which enables the use of the whole set of nuclear coordinates in computations and
      the inclusion of both the effects of the equilibrium position displacements and
      of normal mode mixing upon hole transfer. The time dependent populations
      predicted by cumulant approach are in good agreement with those obtained by
      numerical solution of time dependent Schrodinger equation, even for ultrafast
      processes, where the Fermi Golden Rule fails.

PMID- 29345938
TI  - PSO Method for Fitting Analytic Potential Energy Functions. Application to I
      (H2O).
AB  - In this work a particle swarm optimization (PSO) algorithm was used to fit an
      analytic potential energy function to I-(H2O) intermolecular potential energy
      curves calculated with DFT/B97-1 theory. The analytic function is a sum of two
      body terms, each written as a generalized sum of Buckingham and Lennard-Jones
      terms with only six parameters. Two models were used to describe the two-body
      terms between I- and H2O: a three-site model H2O and a four-site model including
      a ghost atom. The fits are compared with those obtained with a genetic/nonlinear
      least-squares algorithm. The ghost atom model significantly improves the fitting
      accuracy for both algorithms. The PSO fits are significantly more accurate and
      much less time-consuming than those obtained with the genetic/nonlinear least
      squares algorithm. Eight I----H2O potential energy curves, fit with the PSO
      algorithm for the three- and four-site models, have RMSE of 1.37 and 0.22
      kcal/mol and compute times of ~20 and ~68 min, respectively. The PSO fit for the
      four-site model is quite adequate for determining densities of states and
      partition functions for I-(H2O) n clusters at high energies and temperatures,
      respectively. The PSO algorithm was also applied to the eight potential energy
      curves, with the four-site model, for a short time ~8 min fitting. The RMSE was
      small, only 0.37 kcal/mol, showing the high efficiency of the PSO algorithm with
      retention of a good fitting accuracy. The PSO algorithm is a good choice for
      fitting analytic potential energy functions, and for the work presented here was
      able to find an adequate fit to an I-(H2O) analytic intermolecular potential with
      a small number of parameters.

PMID- 29345940
TI  - Environment-Modulated Crystallization of Cu2O and CuO Nanowires by
      Electrospinning and Their Charge Storage Properties.
AB  - This article reports the synthesis of cuprous oxide (Cu2O) and cupric oxide (CuO)
      nanowires by controlling the calcination environment of electrospun polymeric
      nanowires and their charge storage properties. The Cu2O nanowires showed higher
      surface area (86 m2 g-1) and pore size than the CuO nanowires (36 m2 g-1).
      Electrochemical analysis was carried out in 6 M KOH, and both the electrodes
      showed battery-type charge storage mechanism. The electrospun Cu2O electrodes
      delivered high discharge capacity (126 mA h g-1) than CuO (72 mA h g-1) at a
      current density of 2.4 mA cm-2. Electrochemical impedance spectroscopy
      measurements show almost similar charge-transfer resistance in Cu2O (1.2 Omega)
      and CuO (1.6 Omega); however, Cu2O showed an order of magnitude higher ion
      diffusion. The difference in charge storage between these electrodes is
      attributed to the difference in surface properties and charge kinetics at the
      electrode. The electrode also shows superior cyclic stability (98%) and Coulombic
      efficiency (98%) after 5000 cycles. Therefore, these materials could be
      acceptable choices as a battery-type or pseudocapacitive electrode in asymmetric
      supercapacitors.

PMID- 29345939
TI  - Discovery of Alternative Producers of the Enediyne Antitumor Antibiotic C-1027
      with High Titers.
AB  - The potent cytotoxicity and unique mode of action make the enediyne antitumor
      antibiotic C-1027 an exquisite drug candidate for anticancer chemotherapy.
      However, clinical development of C-1027 has been hampered by its low titer from
      the original producer Streptomyces globisporus C-1027. Here we report three new C
      1027 alternative producers, Streptomyces sp. CB00657, CB02329, and CB03608, from
      The Scripps Research Institute actinomycetes strain collection. Together with the
      previously disclosed Streptomyces sp. CB02366 strain, four C-1027 alternative
      producers with C-1027 titers of up to 11-fold higher than the original producer
      have been discovered. The five C-1027 producers, isolated from distant geographic
      locations, are distinct Streptomyces strains based on morphology and taxonomy.
      Pulsed-field gel electrophoresis and Southern analysis of the five C-1027
      producers reveal that their C-1027 biosynthetic gene clusters (BGCs) are all
      located on giant plasmids of varying sizes. The high nucleotide sequence
      similarity among the five C-1027 BGCs implies that they most likely have evolved
      from a common ancestor.

PMID- 29345941
TI  - Dual Signaling DNA Electrochemistry: An Approach To Understand DNA Interfaces.
AB  - Electrochemical DNA biosensors composed of a redox marker modified nucleic acid
      probe tethered to a solid electrode is a common experimental construct for
      detecting DNA and RNA targets, proteins, inorganic ions, and even small
      molecules. This class of biosensors generally relies on the binding-induced
      conformational changes in the distance of the redox marker relative to the
      electrode surface such that the charge transfer is altered. The conventional
      design is to attach the redox species to the distal end of a surface-bound
      nucleic acid strand. Here we show the impact of the position of the redox marker,
      whether on the distal or proximal end of the DNA monolayer, on the DNA interface
      electrochemistry. Somewhat unexpectedly, greater currents were obtained when the
      redox molecules were located on the distal end of the surface-bound DNA
      monolayer, notionally furthest away from the electrode, compared with currents
      when the redox species were located on the proximal end, close to the electrode.
      Our results suggest that a limitation in ion accessibility is the reason why
      smaller currents were obtained for the redox markers located at the bottom of the
      DNA monolayer. This understanding shows that to allow the quantification of the
      amount of redox labeled target DNA strand that hybridizes to probe DNA
      immobilized on the electrode surface, the redox species must be on the distal end
      of the surface-bound duplex.

PMID- 29345942
TI  - Highly Stereoselective 2-Oxonia-Cope Rearrangement: A Platform Enabling At-Will
      Control of Regio-, Enantio-, and Diastereoselectivity in the Vinylogous Aldol
      Reactions of Aldehydes.
AB  - A distinctly different approach for the vinylogous aldolation of aldehydes is
      described, which exploits 2-oxonia-Cope rearrangement reactions between two
      readily available partners, a set of rationally designed chiral homoallylic
      alcohol synthons and aldehydes, under simple conditions. In these processes,
      chirality transfer from the former to the latter is nearly perfect, giving rise
      to excellent enantio- and diastereoselectivity without the regioselectivity issue
      associated with traditional vinylogous aldol reactions.

PMID- 29345944
TI  - Correction to Nanoscale Control of Morphology in Fullerene-Based Electron
      Conducting Buffers via Organic Vapor Phase Deposition.

PMID- 29345943
TI  - Oxycyanation of Vinyl Ethers with 2,2,6,6-Tetramethyl-N-oxopiperidinium Enabled
      by Electron Donor-Acceptor Complex.
AB  - An efficient and mild oxycyanation of vinyl ethers with 2,2,6,6-tetramethyl-N
      oxopiperidinium and TMSCN is described. The mechanistic studies indicated that
      the formation of an electron donor-acceptor complex and subsequent single
      electron-transfer process could be involved in the reaction.

PMID- 29345945
TI  - Chitosan-Silica Hybrid Composites for Removal of Sulfonated Azo Dyes from Aqueous
      Solutions.
AB  - In this study, the influence of the chitosan immobilization method on the
      properties of final hybrid materials was performed. Chitosan was immobilized on
      the surface of mesoporous (ChS2) and fumed silica (ChS3) by physical adsorption
      and the sol-gel method (ChS1). It was found that physical immobilization of
      chitosan allows to obtain hybrid composites (ChS) with a homogeneous distribution
      of polymer on the surface, relatively wide pores, and specific surface area of
      about 170 m2/g, pHPZC = 5.7 for ChS3 and 356 m2/g and pHPZC = 6.0 for ChS2. The
      microporous chitosan-silica material with a specific surface area of 600 m2/g and
      a more negatively charged surface (pHPZC = 4.2) was obtained by the sol-gel
      reaction. The mechanisms of azo dye adsorption were studied, and the correlation
      with the composite structure was distinguished. The generalized Langmuir equation
      and its special cases, that is, Langmuir-Freundlich and Langmuir equations, were
      applied for the analysis of adsorption isotherm data. The adsorption study showed
      that physically adsorbed chitosan (ChS1 and ChS2) on a silica surface has a
      higher sorption capacity, for example, 0.48 mmol/g for the acid red 88 (AR88) dye
      (ChS2) and 0.23 mmol/g for the acid orange 8 (AO8) dye (ChS1), compared to the
      composite obtained by the sol-gel method [ChS1, 0.05 mmol/g for the AO8 dye]. For
      a deeper understanding of the behavior of immobilized chitosan in the adsorption
      processes, various kinetic equations were applied: first-order, second-order,
      mixed 1,2-order (MOE), multiexponential, and fractal-like MOE as well as
      intraparticle and pore diffusion model equations. In the case of AO8 dye, the
      adsorption rates were differentiated for three composites: for ChS3, 50% of the
      dye was removed from the solution after merely 5 min and almost 90% after 80 min.
      The slowest adsorption process controlled by the diffusion rate of dye molecules
      into the internal space of the pore structure was found for ChS1 (225 min
      halftime). In the case of ChS2, the rates for various dyes change in the
      following order: acid orange (AO7) > orange G (OG) > acid red 1 (AR1) > AR88 >
      AO8 (halftimes: 10.5 < 15.7 < 23.7 < 34.9 < 42.9 min).

PMID- 29345946
TI  - Cooperative Metal-Ligand Catalyzed Intramolecular Hydroamination and
      Hydroalkoxylation of Allenes Using a Stable Iron Catalyst.
AB  - A new iron-catalyzed chemoselective intramolecular hydroamination and
      hydroalkoxylation of the readily available alpha-allenic amines and alcohols to
      valuable unsaturated 5-membered heterocycles, 2,3-dihydropyrrole and 2,3
      dihydrofuran, is reported. Effective selectivity control is achieved by a metal
      ligand cooperative activation of the substrates. The mild reaction conditions and
      the use of low amounts of an air and moisture stable iron catalyst allow for the
      hydrofunctionalization of a wide range of allenes bearing different functional
      groups in good yields in the absence of base or any sensitive additives.

PMID- 29345947
TI  - Nucleophilic Ring Opening of Donor-Acceptor Cyclopropanes Catalyzed by a Bronsted
      Acid in Hexafluoroisopropanol.
AB  - A general, Bronsted acid catalyzed method for the room temperature, nucleophilic
      ring opening of donor-acceptor cyclopropanes in fluorinated alcohol solvent,
      HFIP, is described. Salient features of this method include an expanded
      cyclopropane scope, including those bearing single keto-acceptor groups and those
      bearing electron-deficient aryl groups. Notably, the catalytic system proved
      amenable to a wide range of nucleophiles including arenes, indoles, azides,
      diketones, and alcohols.

PMID- 29345948
TI  - Matched Coupling of Propargylic Carbonates with Cyclopropanols.
AB  - The ring opening-coupling reaction of cyclopropanols with propargylic carbonates
      affording synthetically attractive allenyl ketones has been developed. The
      mechanism involves the ligand-exchange reaction of in situ formed allenyl
      palladium methoxide with cyclopropanols followed by carbon-carbon bond cleavage
      and reductive elimination. The reactions proceeded smoothly under mild reaction
      conditions with Pd(0)/XPhos catalysis in the absence of any external base and
      displayed a wide scope and application to a steroidal skeleton. The efficiency of
      chirality transfer and synthetic utility of the allene products have also been
      demonstrated.

PMID- 29345949
TI  - Surface State Dynamics Dictating Transport in InAs Nanowires.
AB  - Because of their high aspect ratio, nanostructures are particularly susceptible
      to effects from surfaces such as slow electron trapping by surface states.
      However, nonequilibrium trapping dynamics have been largely overlooked when
      considering transport in nanoelectronic devices. In this study, we demonstrate
      the profound influence of dynamic trapping processes on transport in InAs
      nanowires through an investigation of the hysteretic and time-dependent behavior
      of the transconductance. We observe large densities (~1013 cm-2) of slow surface
      traps and demonstrate the ability to control and permanently fix their occupation
      and charge through electrostatic manipulation by the gate potential followed by
      thermal deactivation by cryogenic cooling. Furthermore, we observe a transition
      from enhancement- to depletion-mode and a 400% change in field-effect mobility
      within the same device when the initial gate voltage and sweep rate are varied,
      revealing the severe impact of electrostatic history and dynamics on InAs
      nanowire field-effect transistors. A time-dependent model for nanowire
      transconductance based on nonequilibrium carrier population dynamics with
      thermally activated capture and emission was constructed and showed excellent
      agreement with experiments, confirming the effects to be a direct result of the
      dynamics of slow surface traps characterized by large thermal activation barriers
      (~ 700 meV). This work reveals a clear and direct link between the electrical
      conductivity and the microscopic interactions of charged species with nanowire
      surfaces and highlights the necessity for considering dynamic properties of
      surface states in nanoelectronic devices.

PMID- 29345950
TI  - Confined Electroconvective Vortices at Structured Ion Exchange Membranes.
AB  - In this paper, we investigate electroconvective ion transport at cation exchange
      membranes with different geometry square-wave structures (line undulations)
      experimentally and numerically. Electroconvective microvortices are induced by
      strong concentration polarization once a threshold potential difference is
      applied. The applied potential required to start and sustain electroconvection is
      strongly affected by the geometry of the membrane. A reduction in the resistance
      of approximately 50% can be obtained when the structure size is similar to the
      mixing layer (ML) thickness, resulting in confined vortices with less lateral
      motion compared to the case of flat membranes. From electrical, flow, and
      concentration measurements, ion migration, advection, and diffusion are
      quantified, respectively. Advection and migration are dominant in the vortex ML,
      whereas diffusion and migration are dominant in the stagnant diffusion layer.
      Numerical simulations, based on Poisson-Nernst-Planck and Navier-Stokes
      equations, show similar ion transport and flow characteristics, highlighting the
      importance of membrane topology on the resulting electrokinetic and
      electrohydrodynamic behavior.

PMID- 29345951
TI  - Visible-Light-Driven Silver-Catalyzed One-Pot Approach: A Selective Synthesis of
      Diaryl Sulfoxides and Diaryl Sulfones.
AB  - An efficient one-pot approach for the synthesis of diaryl sulfoxides and diaryl
      sulfones using aryl thiols and aryl diazonium salts was developed. The use of a
      visible-light-driven silver catalysis and the subsequent singlet-oxygen-induced
      oxidation enabled selective synthesis of sulfoxides and sulfones in the absence
      of a photocatalyst. The reactions were carried out under mild reaction
      conditions; the desired products were obtained under air atmosphere at room
      temperature.

PMID- 29345952
TI  - Visible-Light-Enabled Preparation of Palladium Nanoparticles and Application as
      Catalysts for Suzuki-Miyaura Coupling.
AB  - Silyl ketones were used for the preparation of palladium nanoparticles (PdNPs)
      starting with Pd(OAc)2 in dimethylformamide under irradiation with a visible
      light-emitting diode (LED). Variation of the silyl ketone structure allowed
      adjustment of the PdNP diameter (1.9 or 5.2 nm). The in situ-formed PdNPs were
      further stabilized with polyvinylpyrrolidone and then applied as recyclable
      catalysts in the Suzuki-Miyaura coupling of arylboronic acids with aryl iodides
      to obtain substituted biphenyls in excellent yields.

PMID- 29345953
TI  - Micro to Nanoscale Engineering of Surface Precipitates Using Reconfigurable
      Contact Lines.
AB  - Nanoscale engineering has traditionally adopted the chemical route of synthesis
      or optochemical techniques such as lithography requiring large process times,
      expensive equipment, and an inert environment. Directed self-assembly using
      evaporation of nanocolloidal droplet can be a potential low-cost alternative
      across various industries ranging from semiconductors to biomedical systems. It
      is relatively simple to scale and reorient the evaporation-driven internal flow
      field in an evaporating droplet which can direct dispersed matter into functional
      agglomerates. The resulting functional precipitates not only exhibit
      macroscopically discernible changes but also nanoscopic variations in the
      particulate assembly. Thus, the evaporating droplet forms an autonomous system
      for nanoscale engineering without the need for external resources. In this
      article, an indigenous technique of interfacial re-engineering, which is both
      simple and inexpensive to implement, is developed. Such re-engineering widens the
      horizon for surface patterning previously limited by the fixed nature of the
      droplet interface. It involves handprinting hydrophobic lines on a hydrophilic
      substrate to form a confinement of any selected geometry using a simple document
      stamp. Droplets cast into such confinements get modulated into a variety of
      shapes. The droplet shapes control the contact line behavior, evaporation
      dynamics, and complex internal flow pattern. By exploiting the dynamic interplay
      among these variables, we could control the deposit's macro- as well as nanoscale
      assembly not possible with simple circular droplets. We provide a detailed
      mechanism of the coupling at various length scales enabling a predictive
      capability in custom engineering, particularly useful in nanoscale applications
      such as photonic crystals.

PMID- 29345954
TI  - Irradiation-Induced Palladium-Catalyzed Decarboxylative Heck Reaction of
      Aliphatic N-(Acyloxy)phthalimides at Room Temperature.
AB  - It is reported that Pd(PPh3)2Cl2 in combination with 4,5-bis(diphenylphosphino)
      9,9-dimethylxanthene (Xantphos) under irradiation of blue LEDs efficiently
      catalyzes a decarboxylative Heck reaction of vinyl arenes and vinyl heteroarenes
      with aliphatic N-(acyloxy)phthalimides at room temperature. A broad scope of
      secondary, tertiary, and quaternary carboxylates, including alpha-amino acid
      derived esters, can be applied as amenable substrates with high
      stereoselectivity. The experimental observation was explained by excitation-state
      reactivity of the palladium complex under irradiation to induce single-electron
      transfer to activate N-(acyloxy)phthalimides, and to suppress undesired beta
      hydride elimination of alkyl palladium intermediates.

PMID- 29345955
TI  - Investigation of Polymer/Surfactant Interactions and Their Impact on Itraconazole
      Solubility and Precipitation Kinetics for Developing Spray-Dried Amorphous Solid
      Dispersions.
AB  - Methods were developed to systematically screen different polymer-surfactant
      combinations for the purpose of enhancing amorphous active pharmaceutical
      ingredient (API) solubility while maintaining its physical stability.
      Itraconazole (ITZ) was chosen as the model API mostly due to its low aqueous
      solubility. Special attention was paid to determine the effect of a reduction in
      the critical micelle concentration (CMC) by specific polymer/surfactant
      combinations on the ITZ solubility and physical stability. However, only a slight
      correlation was actually found. Only the polymer/surfactant combinations with the
      smallest effect on CMC improved solubility and stability of ITZ in simulated
      intestinal fluids (SIF). Surfactants were found to negate the stabilizing effects
      of polymers. ITZ crystallization tendency generally depended on the degree of
      supersaturation and the type of polymer/surfactant combinations used. In general,
      we found that instead of focusing solely on reducing the CMC, a systematic
      screening of systems that maintain high ITZ supersaturation proved to be a
      successful approach.

PMID- 29345956
TI  - Measuring Three-Dimensional Strain and Structural Defects in a Single InGaAs
      Nanowire Using Coherent X-ray Multiangle Bragg Projection Ptychography.
AB  - III-As nanowires are candidates for near-infrared light emitters and detectors
      that can be directly integrated onto silicon. However, nanoscale to microscale
      variations in structure, composition, and strain within a given nanowire, as well
      as variations between nanowires, pose challenges to correlating microstructure
      with device performance. In this work, we utilize coherent nanofocused X-rays to
      characterize stacking defects and strain in a single InGaAs nanowire supported on
      Si. By reconstructing diffraction patterns from the 2110 Bragg peak, we show that
      the lattice orientation varies along the length of the wire, while the strain
      field along the cross-section is largely unaffected, leaving the band structure
      unperturbed. Diffraction patterns from the 0110 Bragg peak are reproducibly
      reconstructed to create three-dimensional images of stacking defects and
      associated lattice strains, revealing sharp planar boundaries between different
      crystal phases of wurtzite (WZ) structure that contribute to charge carrier
      scattering. Phase retrieval is made possible by developing multiangle Bragg
      projection ptychography (maBPP) to accommodate coherent nanodiffraction patterns
      measured at arbitrary overlapping positions at multiple angles about a Bragg
      peak, eliminating the need for scan registration at different angles. The
      penetrating nature of X-ray radiation, together with the relaxed constraints of
      maBPP, will enable the in operando imaging of nanowire devices.

PMID- 29345957
TI  - Besifloxacin: A Critical Review of Its Characteristics, Properties, and
      Analytical Methods.
AB  - Bacterial conjunctivitis has high impact on the health of the population, since
      it represents more than a third of ocular pathologies reported by health services
      worldwide. There is a high incidence of bacterial resistance to the
      antimicrobials most commonly used for the treatment of conjunctivitis. In this
      context, besifloxacin stands out, since it is a fluoroquinolone developed
      exclusively for topical ophthalmic use, presenting a low risk of developing
      resistance due to its reduced systemic exposure. Bausch & Lomb markets it as
      ophthalmic suspension, under the trade name BesivanceTM. Literature review on
      besifloxacin is presented, covering its pharmaceutical and clinical
      characteristics, and the analytical methods used to measure the drug in
      pharmaceutical products and biological samples. High performance liquid
      chromatography is the most used method for this purpose. A discussion on Green
      Chemistry is also presented, focusing the importance of the development of green
      analytical methods for the analysis of drugs.

PMID- 29345958
TI  - Plasma Cell Variant Multicentric Castleman Disease and Kaposi's Sarcoma in a
      Treatment-Naive HIV-Infected Patient.

PMID- 29345959
TI  - Have We Not Learned from Past Mistakes?

PMID- 29345960
TI  - Pacing strategies by age in marathon cross-country skiing.
AB  - OBJECTIVES: Pacing strategies have mainly been investigated for runners, but
      little is known for cross-country skiers. The aim of the present study was to
      investigate whether differences in pacing strategies do exist between younger and
      older cross-country skiers competing in the 42 km 'Engadin Ski Marathon'.
      METHODS: Pacing was studied in 105,565 cross-country skiers (classified in 5-year
      age groups) competing between 1998 and 2016 in this race by examining changes of
      mean section velocity in 10 km (Change A, i.e. 100*(velocity in the 10-20 km
      section - velocity in the 0-10 km section)/velocity in the 0-10 km section), 20
      km (Change B) and 35 km (Change C). RESULTS: A small sex*distance (i.e. Change A
      versus Change B versus Change C) interaction on change of velocity was shown (P <
      .001, eta2 = 0.016), with women showing a less even pacing than men. In women,
      there was a trivial main effect of age group on Change A (P < .001, eta2 = 0.008)
      with a smaller decrease in velocity in age group <20 (-7.4%) and larger decrease
      in velocity in age group 75-79 (-12.8%), and Change B (P = .006, eta2 = 0.004)
      with smaller increase in velocity in age group 75-79 (+30.6%) and larger increase
      in velocity in age group 40-44 (+37.7%), but not on Change C (P = .784, eta2 =
      0.003). In men, a small main effect of age group on Change A was shown (P < .001,
      eta2 = 0.019), with a smaller decrease of velocity in age group <20 (-3.5%) and
      larger in age group 70-74 (-10.5%). Trivial main effects of age group on Change B
      (P < .001, eta2 = .002), with a smaller increase of velocity in age group 85-89
      (+25.8%) and larger increase in age group 70-74 (+33.0%), and Change C (P < .001,
      eta2 = 0.003), with smaller decrease of velocity in age group 85-89 (-38.2%) and
      larger decrease in age group 80-84 (-41.0%), were found. CONCLUSIONS: Based on
      these findings, it was concluded that men and young cross-country skiers had a
      more even pacing than women and older cross-country skiers, which was in contrast
      with previous findings in other endurance sports, suggesting that the sex- and
      age-related differences in pacing might be sport-dependent.

PMID- 29345961
TI  - Effects of Quercetin, Kaempferol, and Exogenous Glutathione on Phospho- and Total
      AKT in 3T3-L1 Preadipocytes.
AB  - Obesity has been reported to be a risk factor for some types of cancer, such as
      prostate and lung. The AKT or PI3K-AKT is a signal transduction pathway that
      promotes survival and growth in response to extracellular signals. The aim of
      this study was to investigate the effects of two flavonoids, quercetin and
      kaempferol, and exogenous glutathione (GSH) on the expressions of phospho- and
      total-AKT levels in 3T3-L1 preadipocytes. Glyceraldehyde 3-phosphate
      dehydrogenase (GAPDH) levels were measured in the treated samples and used as the
      internal standard. 3T3-L1 preadipocytes were exposed to each flavonoid and GSH at
      concentrations of 0, 5, 10, 15, 20, and 25 uM, and the levels of phospho- and
      total-Akt were measured by the MILLIPLEX MAP mates protocol, based on the Luminex
      xMAP technology (Millipore Corp., St. Charles, MI, USA). GAPDH levels in the
      preadipocytes were not significantly different at the doses tested for the
      flavonoids and exogenous GSH. However, significant (p <.05) decreases in phospho
      AKT levels in cells treated with quercetin, kaempferol, and GSH at certain doses
      were observed compared to their respective controls. Total-AKT levels showed the
      same profile for all the tested compounds. Significant (p <.01) differences were
      observed for kaempferol (15-25 uM), quercetin at 10 and 20 uM, and GSH at 10 uM
      compared to their respective controls. Findings suggest that exposure of 3T3-L1
      preadipocytes to quercetin, kaempferol, and GSH may block the activation of AKT,
      suggesting the role such compounds play in cell differentiation in 3T3-L1 cells.

PMID- 29345962
TI  - Role of selected polymorphisms in determining muscle fiber composition in
      Japanese men and women.
AB  - Genetic polymorphisms and sex differences are suggested to affect muscle fiber
      composition; however, no study has investigated the effects of genetic
      polymorphisms on muscle fiber composition with respect to sex differences.
      Therefore, the present study examined the effects of genetic polymorphisms on
      muscle fiber composition with respect to sex differences in the Japanese
      population. The present study included 211 healthy Japanese individuals (102 men
      and 109 women). Muscle biopsies were obtained from the vastus lateralis to
      determine the proportion of myosin heavy chain (MHC) isoforms (MHC-I, MHC-IIa,
      and MHC-IIx). Moreover, we analyzed polymorphisms in alpha-actinin-3 gene (
      ACTN3; rs1815739 ), angiotensin-converting enzyme gene ( ACE; rs4341 ), hypoxia
      inducible factor 1 alpha gene ( rs11549465 ), vascular endothelial growth factor
      receptor 2 gene ( rs1870377 ), and angiotensin II receptor, type 2 gene (
      rs11091046 ), by TaqMan single-nucleotide polymorphism genotyping assays. The
      proportion of MHC-I was 9.8% lower in men than in women, whereas the proportion
      of MHC-IIa and MHC-IIx was higher in men than in women (5.0 and 4.6%,
      respectively). Men with the ACTN3 RR + RX genotype had a 4.8% higher proportion
      of MHC-IIx than those with the ACTN3 XX genotype. Moreover, men with the ACE ID +
      DD genotype had a 4.7% higher proportion of MHC-I than those with the ACE II
      genotype. Furthermore, a combined genotype of ACTN3 R577X and ACE
      insertion/deletion (I/D) was significantly correlated with the proportion of MHC
      I ( r = -0.23) and MHC-IIx ( r = 0.27) in men. In contrast, no significant
      correlation was observed between the examined polymorphisms and muscle fiber
      composition in women. These results suggest that the ACTN3 R577X and ACE I/D
      polymorphisms independently affect the proportion of human skeletal muscle fibers
      MHC-I and MHC-IIx in men but not in women. NEW & NOTEWORTHY In men, the RR + RX
      genotype of the alpha-actinin-3 gene ( ACTN3) R577X polymorphism was associated
      with a higher proportion of myosin heavy chain (MHC)-IIx. The ID + DD genotype of
      the angiotensin-converting enzyme gene ( ACE) insertion/deletion (I/D)
      polymorphism, in contrast to a previous finding, was associated with a higher
      proportion of MHC-I in men. In addition, the combined genotype of these
      polymorphisms was correlated with the proportion of MHC-I and MHC-IIx in men.
      Thus ACTN3 R577X and ACE I/D polymorphisms influence the muscle fiber composition
      in Japanese men.

PMID- 29345963
TI  - Deletion of estrogen receptor alpha in skeletal muscle results in impaired
      contractility in female mice.
AB  - Estradiol deficiency in females can result in skeletal muscle strength loss, and
      treatment with estradiol mitigates the loss. There are three primary estrogen
      receptors (ERs), and estradiol elicits effects through these receptors in various
      tissues. Ubiquitous ERalpha-knockout mice exhibit numerous biological disorders,
      but little is known regarding the specific role of ERalpha in skeletal muscle
      contractile function. The purpose of this study was to determine the impact of
      skeletal muscle-specific ERalpha deletion on contractile function, hypothesizing
      that ERalpha is a main receptor through which estradiol affects muscle strength
      in females. Deletion of ERalpha specifically in skeletal muscle (skmERalphaKO)
      did not affect body mass compared with wild-type littermates (skmERalphaWT) until
      26 wk of age, at which time body mass of skmERalphaKO mice began to increase
      disproportionally. Overall, skmERalphaKO mice had low strength demonstrated in
      multiple muscles and by several contractile parameters. Isolated extensor
      digitorum longus muscles from skmERalphaKO mice produced 16% less eccentric and
      16-26% less submaximal and maximal isometric force, and isolated soleus muscles
      were more fatigable, with impaired force recovery relative to skmERalphaWT mice.
      In vivo maximal torque productions by plantarflexors and dorsiflexors were 16%
      and 12% lower in skmERalphaKO than skmERalphaWT mice, and skmERalphaKO muscles
      had low phosphorylation of myosin regulatory light chain. Plantarflexors also
      generated 21-32% less power, submaximal isometric and peak concentric torques.
      Data support the hypothesis that ablation of ERalpha in skeletal muscle results
      in muscle weakness, suggesting that the beneficial effects of estradiol on muscle
      strength are receptor mediated through ERalpha. NEW & NOTEWORTHY We
      comprehensively measured in vitro and in vivo skeletal muscle contractility in
      female estrogen receptor alpha (ERalpha) skeletal muscle-specific knockout mice
      and report that force generation is impaired across multiple parameters. These
      results support the hypothesis that a primary mechanism through which estradiol
      elicits its effects on strength is mediated by ERalpha. Evidence is presented
      that estradiol signaling through ERalpha appears to modulate force at the
      molecular level via posttranslational modifications of myosin regulatory light
      chain.

PMID- 29345965
TI  - The case for exploring the usage of employee wellness programs for pediatric
      asthma control.
AB  - The multiple socioecological determinants of asthma mandate that pediatricians
      develop a treatment strategy beyond the practice-based setting. To expand to a
      more impactful community-based role, pediatricians must look to form partnerships
      with groups that are capable of promoting social and environmental change.
      Traditionally, these groups have included schools, governmental agencies, and
      child care establishments. One group that is not actively being availed of are
      employers who have shown success in improving adult-based outcomes through
      wellness programs. Employers are stakeholders in pediatric asthma care through
      its impact on reduced worker productivity and higher health insurance premiums.
      An employer's focus on pediatric asthma will be a collective win for the employer
      and employee. The article herein describes the rationale for the focus of
      employers on pediatric asthma care and potential incorporation within employer
      based wellness strategies.

PMID- 29345966
TI  - No Room for Error in Medicine-A Case of Deja Vu.

PMID- 29345967
TI  - Reclassifying Acute Respiratory Distress Syndrome.
AB  - RATIONALE: The ratio of PaO2 to FiO2 (P/F) defines acute respiratory distress
      syndrome (ARDS) severity and suggests appropriate therapies. OBJECTIVES: We
      investigated 1) whether a 150-mm-Hg P/F threshold within the range of moderate
      ARDS (100-200 mm Hg) would define two subgroups that were more homogeneous; and
      2) which criteria led the clinicians to apply extracorporeal membrane oxygenation
      (ECMO) in severe ARDS. METHODS: At the 150-mm-Hg P/F threshold, moderate patients
      were split into mild-moderate (n = 50) and moderate-severe (n = 55) groups.
      Patients with severe ARDS (FiO2 not available in three patients) were split into
      higher (n = 63) and lower (n = 18) FiO2 groups at an 80% FiO2 threshold.
      MEASUREMENTS AND MAIN RESULTS: Compared with mild-moderate ARDS, patients with
      moderate-severe ARDS had higher peak pressures, PaCO2, and pH. They also had
      heavier lungs, greater inhomogeneity, more noninflated tissue, and greater lung
      recruitability. Within 84 patients with severe ARDS (P/F < 100 mm Hg), 75%
      belonged to the higher FiO2 subgroup. They differed from the patients with severe
      ARDS with lower FiO2 only in PaCO2 and lung weight. Forty-one of 46 patients
      treated with ECMO belonged to the higher FiO2 group. Within this group, the
      patients receiving ECMO had higher PaCO2 than the 22 non-ECMO patients. The
      inhomogeneity ratio, total lung weight, and noninflated tissue were also
      significantly higher. CONCLUSIONS: Using the 150-mm-Hg P/F threshold gave a more
      homogeneous distribution of patients with ARDS across the severity subgroups and
      identified two populations that differed in their anatomical and physiological
      characteristics. The patients treated with ECMO belonged to the severe ARDS
      group, and almost 90% of them belonged to the higher FiO2 subgroup.

PMID- 29345968
TI  - Mature gastric chief cells are not required for the development of metaplasia.
AB  - During human gastric carcinogenesis, intestinal metaplasia is frequently seen in
      the atrophic stomach. In mice, a distinct type of metaplasia known as spasmolytic
      polypeptide-expressing metaplasia (SPEM) is found in several inflammatory and
      genetically engineered models. Given the diversity of long- and short-term models
      of mouse SPEM, it remains unclear whether all models have a shared or distinct
      molecular mechanism. The origin of SPEM in mice is presently under debate. It is
      postulated that stem or progenitor cells acquire genetic alterations that then
      supply metaplastic cell clones, whereas the possibility of transdifferentiation
      or dedifferentiation from mature gastric chief cells has also been suggested. In
      this study, we report that loss of chief cells was sufficient to induce short
      term regenerative SPEM-like lesions that originated from chief cell precursors in
      the gastric neck region. Furthermore, Lgr5+ mature chief cells failed to
      contribute to both short- and long-term metaplasia, whereas isthmus stem and
      progenitor cells efficiently contributed to long-term metaplasia. Interestingly,
      multiple administrations of high-dose pulsed tamoxifen induced expansion of Lgr5
      expression and Lgr5-CreERT recombination within the isthmus progenitors apart
      from basal chief cells. Thus we conclude that short-term SPEM represents a
      regenerative process arising from neck progenitors following chief cell loss,
      whereas true long-term SPEM originates from isthmus progenitors. Mature gastric
      chief cells may be dispensable for SPEM development. NEW & NOTEWORTHY Recently,
      dedifferentiation ability in gastric chief cells during metaplasia development
      has been proposed. Our findings reveal that lesions that were thought to be acute
      metaplasia in fact represent normal regeneration supplied from neck lineage and
      that isthmus stem/progenitors are more responsible for sustained metaplastic
      changes. Cellular plasticity in gastric chief cells may be more limited than
      recently highlighted.

PMID- 29345964
TI  - Immune Response to Dengue and Zika.
AB  - Flaviviruses such as dengue (DENV), yellow fever (YFV), West Nile (WNV), and Zika
      (ZIKV) are human pathogens of global significance. In particular, DENV causes the
      most prevalent mosquito-borne viral diseases in humans, and ZIKV emerged from
      obscurity into the spotlight in 2016 as the etiologic agent of congenital Zika
      syndrome. Owing to the recent emergence of ZIKV as a global pandemic threat, the
      roles of the immune system during ZIKV infections are as yet unclear. In
      contrast, decades of DENV research implicate a dual role for the immune system in
      protection against and pathogenesis of DENV infection. As DENV and ZIKV are
      closely related, knowledge based on DENV studies has been used to prioritize
      investigation of ZIKV immunity and pathogenesis, and to accelerate ZIKV
      diagnostic, therapeutic, and vaccine design. This review discusses the following
      topics related to innate and adaptive immune responses to DENV and ZIKV: the
      interferon system as the key mechanism of host defense and viral target for
      immune evasion, antibody-mediated protection versus antibody-dependent
      enhancement, and T cell-mediated protection versus original T cell antigenic sin.
      Understanding the mechanisms that regulate the balance between immune-mediated
      protection and pathogenesis during DENV and ZIKV infections is critical toward
      development of safe and effective DENV and ZIKV therapeutics and vaccines.

PMID- 29345969
TI  - Reply to Dahm et al., to Shah et al., and to Schunemann and Brozek.

PMID- 29345971
TI  - A Blast from the Past-Back to the 1970s.

PMID- 29345970
TI  - The Prevalence and Significance of Staphylococcus aureus in Patients with Non
      Cystic Fibrosis Bronchiectasis.
AB  - RATIONALE: Staphylococcus aureus is commonly cultured from the sputum of patients
      with bronchiectasis; however, little is known about the prevalence of the
      organism in these patients, the characteristics of patients who have grown the
      organism, or its implications. OBJECTIVES: Determine the relationship between S.
      aureus and pulmonary function, frequency of exacerbations, and frequency of
      hospitalization in patients with bronchiectasis Methods: The Bronchiectasis
      Research Registry is a database of adults with non-cystic fibrosis bronchiectasis
      identified from 13 sites within the United States. Baseline and follow-up
      demographic, spirometric, microbiologic, and therapeutic data were entered into a
      central web-based database. Patients were grouped into three cohorts based on
      their previous respiratory cultures at the time of entry into the Registry: 1) no
      prior S. aureus or glucose-nonfermenting gram-negative bacilli (NF-GNB)
      (Pseudomonas, Stenotrophomonas, or Burkholderia spp.); 2) prior S. aureus at
      least once; or 3) no prior S. aureus but prior NF-GNB at least once. The
      association between S. aureus isolation and pulmonary function and frequency of
      exacerbations and hospital admissions was assessed, both at baseline and after 1
      year of follow-up. RESULTS: S. aureus was cultured from 94 of 830 patients
      (11.3%) included in the analysis. Patients who had grown S. aureus before entry
      into the Registry had a frequency of prior exacerbations and baseline pulmonary
      function that was between that of patients who had grown NF-GNB and those who had
      grown neither NF-GNB or S. aureus. Similarly, at the first follow-up visit after
      study entry, patients who had grown S. aureus had a frequency of exacerbations
      and hospitalizations that was between those of patients who had grown NF-GNB and
      those who had grown neither NF-GNB nor S. aureus. However, in multivariate
      analysis, S. aureus was not associated with pulmonary function, frequency of
      exacerbation, or hospital admissions. There were no significant differences in
      patient characteristics or outcomes between patients who had methicillin
      sensitive and methicillin-resistant S. aureus. CONCLUSIONS: Staphylococcus aureus
      does not appear to be an independent risk factor for severe disease in patients
      with bronchiectasis enrolled in the Bronchiectasis Research Registry.

PMID- 29345972
TI  - Trypsin Inhibitors from Cajanus cajan and Phaseolus limensis Possess Antioxidant,
      Anti-Inflammatory, and Antibacterial Activity.
AB  - Protease inhibitors are one of the most promising and investigated subjects for
      their role in pharmacognostic and pharmacological studies. This study aimed to
      investigate antioxidant, anti-inflammatory, and antimicrobial activities of
      trypsin inhibitors (TIs) from two plant sources (Cajanus cajan and Phaseolus
      limensis). TI was purified from C. cajan (PUSA-992) by ammonium sulfate
      precipitation followed by ion exchange chromatography. TI from Phaseolus limensis
      (lima bean trypsin inhibitor; LBTI) was procured from Sigma-Aldrich, St. Louis,
      Missouri, United States. The antioxidant activity was analyzed by ferric ion
      reducing antioxidant power (FRAP) and 2,2-diphenyl-1-picrylhydrazyl (DPPH). The
      anti-inflammatory property of TIs was determined by inhibition of albumin
      denaturation assay. Ascorbic acid and aspirin were used as standards for
      antioxidant and anti-inflammatory assays, respectively. These TIs were tested
      against various bacterial and fungal strains. The TIs showed DPPH radical
      scavenging activity in a concentration-dependent manner with IC50 values
      comparable to ascorbic acid. The FRAP values were also observed comparable to
      ascorbic acid and followed the trend of dose-dependent manner. The half maximal
      inhibitory concentration (IC50) values of CCTI and LBTI in anti-inflammatory test
      showed that LBTI is more potent than CCTI. The TIs showed potent antibacterial
      activity, but apparently no action against fungi. This study has reported the
      biological properties of CCTI and LBTI for the first time. The results show that
      TIs possess the ability to inhibit diseases caused by oxidative stress,
      inflammation, and bacterial infestation.

PMID- 29345973
TI  - R-Spondin-2 Is Upregulated in Idiopathic Pulmonary Fibrosis and Affects
      Fibroblast Behavior.
AB  - Idiopathic pulmonary fibrosis (IPF) is characterized by the expansion of the
      myofibroblast population, excessive extracellular matrix accumulation, and
      destruction of the lung parenchyma. The R-spondin family (RSPO) comprises a group
      of proteins essential for development. Among them, RSPO2 is expressed primarily
      in the lungs, and its mutations cause severe defects in the respiratory tract.
      Interestingly, RSPO2 participates in the canonical Wingless/int1 pathway, a
      critical route in the pathogenesis of IPF. Thus, the aim of this study was to
      examine the expression and putative role of RSPO2 in this disease. We found that
      RSPO2 and its receptor leucine-rich G protein-coupled receptor 6 were upregulated
      in IPF lungs, where they localized primarily in fibroblasts and epithelial cells.
      Stimulation of IPF and normal lung fibroblasts with recombinant human RSPO2
      resulted in the deregulation of numerous genes, although the transcriptional
      response was essentially distinct. In IPF fibroblasts, RSPO2 stimulation induced
      the up- or downregulation of several genes involved in the Wingless/int1 pathway
      (mainly from noncanonical signaling). In both normal and IPF fibroblasts, RSPO2
      modifies the expression of genes implicated in several pathways, including the
      cell cycle and apoptosis. In accordance with gene expression, the stimulation of
      normal and IPF fibroblasts with RSPO2 significantly reduced cell proliferation
      and induced cell death. RSPO2 also inhibited collagen production and increased
      the expression of matrix metalloproteinase 1. Silencing RSPO2 with shRNA induced
      the opposite effects. Our findings demonstrate, for the first time to our
      knowledge, that RSPO2 is upregulated in IPF, where it appears to have an
      antifibrotic role.

PMID- 29345974
TI  - Cognitive Effects of Cancer and Cancer Treatments.
AB  - As the population of cancer survivors has grown into the millions, there has been
      increasing emphasis on understanding how the late effects of treatment affect
      survivors' ability to return to work/school, their capacity to function and live
      independently, and their overall quality of life. This review focuses on
      cognitive change associated with cancer and cancer treatments. Research in this
      area has progressed from a pharmacotoxicology perspective to a view of the
      cognitive change as a complex interaction of aspects of the treatment,
      vulnerability factors that increase risk for posttreatment cognitive decline,
      cancer biology, and the biology of aging. Methodological advances include the
      development of (a) measurement approaches that assess more fine-grained
      subcomponents of cognition based on cognitive neuroscience and (b) advanced
      statistical approaches. Conceptual issues that arise from this multidimensional
      perspective are described in relation to future directions, understanding of
      mechanisms, and development of innovative interventions.

PMID- 29345975
TI  - Nano- and micro-particles for delivery of catechins: Physical and biological
      performance.
AB  - Catechins, present in many fruits and vegetables, have many health benefits, but
      they are prone to degradation. Nano- and micro-particle systems have been used to
      stabilise catechins when exposed to adverse environments and to improve their
      bioavailability after ingestion. This review discusses the inherent properties of
      various catechins, the design of delivery formulations and the properties of
      catechin-loaded nano- and micro-particles. The protection afforded to catechins
      during exposure to harsh environmental conditions and gastrointestinal tract
      transit is reviewed. The bioavailability and efficacy of encapsulated catechins,
      as assessed by various in vitro and in vivo conditions, are discussed.
      Bioavailability based on uptake in the upper gut alone underestimates the
      bioavailability as polyphenols. The caveats with interpretation of
      bioavailability based on various tests are discussed, when taking into
      consideration the pathways of catechin metabolism including the role of the gut
      microflora. However, taken together, the weight of the evidence suggests that
      there are potentially improved health benefits with the use of appropriately
      designed nano- and micro-particles for delivery of catechins. Further systematic
      studies on the metabolism and physiological effects of encapsulated catechins in
      vivo and clinical trials are needed to validate the bioefficacy of the
      encapsulated catechins.

PMID- 29345976
TI  - Synthetic Biology: Immunotherapy by Design.
AB  - Cellular immunotherapy holds great promise for the treatment of human disease.
      Clinical evidence suggests that T cell immunotherapies have the potential to
      combat cancers that evade traditional immunotherapy. Despite promising results,
      adverse effects leading to fatalities have left scientists seeking tighter
      control over these therapies, which is reflected in the growing body of synthetic
      biology literature focused on developing tightly controlled, context-independent
      parts. In addition, researchers are adapting these tools for other uses, such as
      for the treatment of autoimmune disease, HIV infection, and fungal interactions.
      We review this body of work and devote special attention to approaches that may
      lend themselves to the development of an "ideal" therapy: one that is safe,
      efficient, and easy to manufacture. We conclude with a look toward the future of
      immunotherapy: how synthetic biology can shift the paradigm from the treatment of
      disease to a focus on wellness and human health as a whole.

PMID- 29345978
TI  - Research in Rare Disease: From Genomics to Proteomics.
AB  - Jessica Lacoste from the Donnelly Centre at the University of Toronto was awarded
      best poster at the annual Society of Biomolecular Imaging and Informatics meeting
      held in San Diego, September 2017. Her work focuses on characterizing the protein
      localization of variants involved in rare disease. The current works and future
      directions of research in rare disease are summarized in the following overview.

PMID- 29345979
TI  - Machine Learning Enables Live Label-Free Phenotypic Screening in Three
      Dimensions.
AB  - There is a large amount of information in brightfield images that was previously
      inaccessible by using traditional microscopy techniques. This information can now
      be exploited by using machine-learning approaches for both image segmentation and
      the classification of objects. We have combined these approaches with a label
      free assay for growth and differentiation of leukemic colonies, to generate a
      novel platform for phenotypic drug discovery. Initially, a supervised machine
      learning algorithm was used to identify in-focus colonies growing in a three
      dimensional (3D) methylcellulose gel. Once identified, unsupervised clustering
      and principle component analysis of texture-based phenotypic profiles were
      applied to group similar phenotypes. In a proof-of-concept study, we successfully
      identified a novel phenotype induced by a compound that is currently in clinical
      trials for the treatment of leukemia. We believe that our platform will be of
      great benefit for the utilization of patient-derived 3D cell culture systems for
      both drug discovery and diagnostic applications.

PMID- 29345977
TI  - Targeted and Nontargeted alpha-Particle Therapies.
AB  - alpha-Particle irradiation of cancerous tissue is increasingly recognized as a
      potent therapeutic option. We briefly review the physics, radiobiology, and
      dosimetry of alpha-particle emitters, as well as the distinguishing features that
      make them unique for radiopharmaceutical therapy. We also review the emerging
      clinical role of alpha-particle therapy in managing cancer and recent studies on
      in vitro and preclinical alpha-particle therapy delivered by antibodies, other
      small molecules, and nanometer-sized particles. In addition to their unique
      radiopharmaceutical characteristics, the increased availability and improved
      radiochemistry of alpha-particle radionuclides have contributed to the growing
      recent interest in alpha-particle radiotherapy. Targeted therapy strategies have
      presented novel possibilities for the use of alpha-particles in the treatment of
      cancer. Clinical experience has already demonstrated the safe and effective use
      of alpha-particle emitters as potent tumor-selective drugs for the treatment of
      leukemia and metastatic disease.

PMID- 29345980
TI  - Society of Biomolecular Imaging and Informatics High-Content Screening/High
      Content Analysis Emerging Technologies in Biological Models, When and Why?

PMID- 29345981
TI  - Correction to: J Endourol 2017;31:985-990.

PMID- 29345982
TI  - Development of a Trio of Potential Biomarkers for Cancer Prognosis.

PMID- 29345983
TI  - No Seat at the Recommendations Table?

PMID- 29345984
TI  - Development of a Polymerase Chain Reaction/Ligase Detection Reaction Assay for
      Detection of CYP2C19 Polymorphisms.
AB  - AIMS: Cytochrome P450 2C19 (CYP2C19) genotypes are associated with differential
      drug metabolism. The aim of this study was to establish a reliable assay for
      CYP2C19 genotyping based on a polymerase chain reaction/ligase detection reaction
      (PCR-LDR). MATERIALS AND METHODS: Specific primers and probes were designed to
      detect CYP2C19*1, *2, *3, and *17. A control for each allele was prepared and
      used for performance evaluation. A total of 200 clinical samples were analyzed
      using the PCR-LDR assay and Sanger sequencing. RESULTS: The detection limit of
      the PCR-LDR assay was 2 ng/MUL of genomic DNA. Common interfering substances in
      the blood did not affect the results of the detection. For the clinical samples,
      the results of the PCR-LDR and the Sanger sequencing were identical. Among the
      200 patients, 104 (52%) were wild type (*1/*1), 64 (32%) were *1/*2, 16 (8%) were
      *1/*3, 8 (4%) were *2/*2, 7 (3.5%) were *2/*3, and 1 (0.5%) was *1/*7. No *3/*3
      genotype was detected in these patients. CONCLUSION: This PCR-LDR assay is
      reliable for the detection of CYP2C19 genotypes in a clinical setting. It will be
      a useful tool to screen for CYP2C19 loss-of-function alleles in patients before
      clopidogrel and proton pump inhibitor treatment.

PMID- 29345985
TI  - CYP3A Activity and Rivaroxaban Serum Concentrations in Russian Patients with Deep
      Vein Thrombosis.
AB  - BACKGROUND: Rivaroxaban is metabolized in the liver via CYP3A4, the cytochrome
      involved in the metabolism of nearly 50% of all medications. Thus, its effective
      concentration depends on multiple pharmacologic parameters. METHODS: The primary
      goal of our research was to study the correlation between the CYP3A family
      activity and the safety and efficacy of anticoagulant therapy with rivaroxaban in
      patients with deep vein thrombosis (DVT). Thirty one patients with DVT aged 21-83
      years, 18 men and 13 women, received rivaroxaban (Xarelto) 30 mg/day for 21 days
      after diagnosis and 20 mg/day for the follow-up period of 6 months. During the
      study period, Doppler ultrasound was performed weekly to assess the clot dynamics
      and recanalization time. RESULTS: We found a direct statistically reliable
      correlation between CYP3A4 activity and both peak and trough rivaroxaban levels.
      A correlation was also found between the initial clot length and the time to full
      recanalization r = 0.764 (0.554-0.883), p < 0.0001. No significant link was found
      between either the glomerular filtration rate and peak rivaroxaban concentrations
      or between CYP3A4 activity and the treatment effectiveness parameters. No
      connection between renal function and rivaroxaban concentration was established
      in our study, which agrees with the clinical trials data that allow unlimited
      rivaroxaban use in patients with glomerular filtration rate >30 mL/min.
      CONCLUSIONS: The direct link between the initial clot length and time to full
      recanalization that has been found means that patients with more advanced stages
      of thrombosis need more time to reach recanalization than their counterparts with
      a less severe condition.

PMID- 29345986
TI  - Vital Signs: Seismology of Icy Ocean Worlds.
AB  - Ice-covered ocean worlds possess diverse energy sources and associated mechanisms
      that are capable of driving significant seismic activity, but to date no
      measurements of their seismic activity have been obtained. Such investigations
      could reveal the transport properties and radial structures, with possibilities
      for locating and characterizing trapped liquids that may host life and yielding
      critical constraints on redox fluxes and thus on habitability. Modeling efforts
      have examined seismic sources from tectonic fracturing and impacts. Here, we
      describe other possible seismic sources, their associations with science
      questions constraining habitability, and the feasibility of implementing such
      investigations. We argue, by analogy with the Moon, that detectable seismic
      activity should occur frequently on tidally flexed ocean worlds. Their ices
      fracture more easily than rocks and dissipate more tidal energy than the <1 GW of
      the Moon and Mars. Icy ocean worlds also should create less thermal noise due to
      their greater distance and consequently smaller diurnal temperature variations.
      They also lack substantial atmospheres (except in the case of Titan) that would
      create additional noise. Thus, seismic experiments could be less complex and less
      susceptible to noise than prior or planned planetary seismology investigations of
      the Moon or Mars. Key Words: Seismology-Redox-Ocean worlds-Europa-Ice
      Hydrothermal. Astrobiology 18, 37-53.

PMID- 29345987
TI  - Habitable Worlds: Delivering on the Promises of Online Education.
AB  - Critical thinking and scientific reasoning are central to higher education in the
      United States, but many courses (in-person and online) teach students information
      about science much more than they teach the actual process of science and its
      associated knowledge and skills. In the online arena specifically, the tools
      available for course construction exacerbate this problem by making it difficult
      to build the types of active learning activities that research shows to be the
      most effective. Here, we present a report on Habitable Worlds, offered by Arizona
      State University for 12 semesters over the past 6 years. This is a unique online
      course that uses an array of novel technologies to deliver an active, inquiry
      driven learning experience. Learning outcomes and quantitative data from more
      than 3000 students demonstrate the success of our approach but also identify
      several remaining challenges. The design and development of this course offers
      valuable lessons for instructional designers and educators who are interested in
      fully capitalizing on the capabilities of 21st-century technology to achieve
      educational goals. Key Words: Online education-Active learning-SETI-Astrobiology
      Teaching. Astrobiology 17, 86-99.

PMID- 29345988
TI  - Measuring Entropy in Molecular Recognition by Proteins.
AB  - Molecular recognition by proteins is fundamental to the molecular basis of
      biology. Dissection of the thermodynamic landscape governing protein-ligand
      interactions has proven difficult because determination of various entropic
      contributions is quite challenging. Nuclear magnetic resonance relaxation
      measurements, theory, and simulations suggest that conformational entropy can be
      accessed through a dynamical proxy. Here, we review the relationship between
      measures of fast side-chain motion and the underlying conformational entropy. The
      dynamical proxy reveals that the contribution of conformational entropy can range
      from highly favorable to highly unfavorable and demonstrates the potential of
      this key thermodynamic variable to modulate protein-ligand interactions. The
      dynamical so-called entropy meter also refines the role of solvent entropy and
      directly determines the loss in rotational-translational entropy that occurs upon
      formation of high-affinity complexes. The ability to quantify the roles of
      entropy through an entropy meter based on measurable dynamical properties
      promises to highlight its role in protein function.

PMID- 29345989
TI  - Assembly of COPI and COPII Vesicular Coat Proteins on Membranes.
AB  - In eukaryotes, distinct transport vesicles functionally connect various
      intracellular compartments. These carriers mediate transport of membranes for the
      biogenesis and maintenance of organelles, secretion of cargo proteins and
      peptides, and uptake of cargo into the cell. Transport vesicles have distinct
      protein coats that assemble on a donor membrane where they can select cargo and
      curve the membrane to form a bud. A multitude of structural elements of coat
      proteins have been solved by X-ray crystallography. More recently, the
      architectures of the COPI and COPII coats were elucidated in context with their
      membrane by cryo-electron tomography. Here, we describe insights gained from the
      structures of these two coat lattices and discuss the resulting functional
      implications.

PMID- 29345990
TI  - Imaging mRNA In Vivo, from Birth to Death.
AB  - RNA is the fundamental information transfer system in the cell. The ability to
      follow single messenger RNAs (mRNAs) from transcription to degradation with
      fluorescent probes gives quantitative information about how the information is
      transferred from DNA to proteins. This review focuses on the latest technological
      developments in the field of single-mRNA detection and their usage to study gene
      expression in both fixed and live cells. By describing the application of these
      imaging tools, we follow the journey of mRNA from transcription to decay in
      single cells, with single-molecule resolution. We review current theoretical
      models for describing transcription and translation that were generated by single
      molecule and single-cell studies. These methods provide a basis to study how
      single-molecule interactions generate phenotypes, fundamentally changing our
      understating of gene expression regulation.

PMID- 29345991
TI  - Collapse Transitions of Proteins and the Interplay Among Backbone, Sidechain, and
      Solvent Interactions.
AB  - Proteins can collapse into compact globules or form expanded, solvent-accessible,
      coil-like conformations. Additionally, they can fold into well-defined three
      dimensional structures or remain partially or entirely disordered. Recent
      discoveries have shown that the tendency for proteins to collapse or remain
      expanded is not intrinsically coupled to their ability to fold. These
      observations suggest that proteins do not have to form compact globules in
      aqueous solutions. They can be intrinsically disordered, collapsed, or expanded,
      and even form well-folded, elongated structures. This ability to decouple
      collapse from folding is determined by the sequence details of proteins. In this
      review, we highlight insights gleaned from studies over the past decade. Using a
      polymer physics framework, we explain how the interplay among sidechains,
      backbone units, and solvent determines the driving forces for collapsed versus
      expanded states in aqueous solvents. 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- 29345992
TI  - The Effect of Patient Navigation on the Likelihood of Engagement in Clinical Care
      for HIV-Infected Individuals Leaving Jail.
AB  - OBJECTIVES: To compare the effectiveness of patient navigation-enhanced case
      management in supporting engagement in HIV care upon release from jail relative
      to existing services. METHODS: We randomized 270 HIV-infected individuals to
      receive navigation-enhanced case management for 12 months or standard case
      management for 90 days following release from jail between 2010 and 2013.
      Participants were interviewed at 2, 6, and 12 months after release. We abstracted
      medical data from jail and city health records. RESULTS: Patient navigation
      enhanced case management resulted in greater linkage to care within 30 days of
      release (odds ratio [OR] = 2.15; 95% confidence interval [CI] = 1.23, 3.75) and
      consistent retention over 12 months (OR = 1.95; 95% CI = 1.11, 3.46). Receipt of
      treatment for substance use disorders in jail also resulted in early linkage (OR
      = 4.06; 95% CI = 1.93, 8.53) and retention (OR = 2.52; 95% CI = 1.21, 5.23).
      Latinos were less likely to be linked to (OR = 0.35; 95% CI = 0.14, 0.91) or
      retained in (OR = 0.28; 95% CI = 0.09, 0.82) HIV care. CONCLUSIONS: Patient
      navigation supports maintaining engagement in care and can mitigate health
      disparities, and should become the standard of care for HIV-infected individuals
      leaving jail.

PMID- 29345993
TI  - Socioeconomic Outcomes of Women Who Receive and Women Who Are Denied Wanted
      Abortions in the United States.
AB  - OBJECTIVES: To determine the socioeconomic consequences of receipt versus denial
      of abortion. METHODS: Women who presented for abortion just before or after the
      gestational age limit of 30 abortion facilities across the United States between
      2008 and 2010 were recruited and followed for 5 years via semiannual telephone
      interviews. Using mixed effects models, we evaluated socioeconomic outcomes for
      813 women by receipt or denial of abortion care. RESULTS: In analyses that
      adjusted for the few baseline differences, women denied abortions who gave birth
      had higher odds of poverty 6 months after denial (adjusted odds ratio [AOR] =
      3.77; P < .001) than did women who received abortions; women denied abortions
      were also more likely to be in poverty for 4 years after denial of abortion. Six
      months after denial of abortion, women were less likely to be employed full time
      (AOR = 0.37; P = .001) and were more likely to receive public assistance (AOR =
      6.26; P < .001) than were women who obtained abortions, differences that remained
      significant for 4 years. CONCLUSIONS: Women denied an abortion were more likely
      than were women who received an abortion to experience economic hardship and
      insecurity lasting years. Laws that restrict access to abortion may result in
      worsened economic outcomes for women.

PMID- 29345994
TI  - Work as an Inclusive Part of Population Health Inequities Research and
      Prevention.
AB  - Despite its inclusion in models of social and ecological determinants of health,
      work has not been explored in most health inequity research in the United States.
      Leaving work out of public health inequities research creates a blind spot in our
      understanding of how inequities are created and impedes our progress toward
      health equity. We first describe why work is vital to our understanding of
      observed societal-level health inequities. Next, we outline challenges to
      incorporating work in the study of health inequities, including (1) the
      complexity of work as a concept; (2) work's overlap with socioeconomic position,
      race, ethnicity, and gender; (3) the development of a parallel line of inquiry
      into occupational health inequities; and (4) the dearth of precise data with
      which to explore the relationships between work and health status. Finally, we
      summarize opportunities for advancing health equity and monitoring progress that
      could be achieved if researchers and practitioners more robustly include work in
      their efforts to understand and address health inequities.

PMID- 29345995
TI  - The Effects of Household Medical Expenditures on Income Inequality in the United
      States.
AB  - OBJECTIVES: To assess the effect of households' outlays for medical expenditures
      on income inequality and changes since the implementation of the Affordable Care
      Act (ACA). METHODS: We analyzed data from the US Current Population Surveys for
      calendar years 2010 through 2014. We calculated the Gini index of income
      inequality before and after subtracting households' medical outlays (including
      insurance premiums and out-of-pocket costs) from income, the financial burden of
      medical outlays for each income decile, and the number of individuals pushed
      below poverty by medical outlays. RESULTS: In 2014, the Gini index was 47.84,
      which rose to 49.21 after medical outlays were subtracted, indicating that
      medical outlays effectively redistributed about 1.37% of total income from poorer
      to richer individuals, a slightly smaller redistribution compared with the years
      before the ACA. Medical outlays reduced the median income of the poorest decile
      by 47.6% versus 2.7% for the wealthiest decile and pushed 7.013 million
      individuals into poverty. CONCLUSIONS: The way we finance medical care
      exacerbates income inequality and impoverishes millions of Americans. This
      regressive financing pattern improved minimally in the wake of the ACA.

PMID- 29345996
TI  - Delays in Global Disease Outbreak Responses: Lessons from H1N1, Ebola, and Zika.
AB  - In global disease outbreaks, there are significant time delays between the source
      of an outbreak and collective action. Some delay is necessary, but recent delays
      have been extended by insufficient surveillance capacity and time-consuming
      efforts to mobilize action. Three public health emergencies of international
      concern (PHEICs)-H1N1, Ebola, and Zika-allow us to identify and compare sources
      of delays and consider seven hypotheses about what influences the length of
      delays. These hypotheses can then motivate further research that empirically
      tests them. The three PHEICs suggest that deferred global mobilization is a
      greater source of delay than is poor surveillance capacity. These case study
      outbreaks support hypotheses that we see quicker responses for novel diseases
      when outbreaks do not coincide with holidays and when US citizens are infected.
      They do not support hypotheses that we see quicker responses for more severe
      outbreaks or those that threaten larger numbers of people. Better understanding
      the reason for delays can help target policy interventions and identify the kind
      of global institutional changes needed to reduce the spread and severity of
      future PHEICs.

PMID- 29345997
TI  - Trends in Health Insurance and Type Among Military Veterans: United States, 2000
      2016.
AB  - OBJECTIVES: To describe long-term national trends in health insurance coverage
      among US veterans from 2000 to 2016 in the context of recent health care reform.
      METHODS: We used 2000 to 2016 National Health Interview Survey data on veterans
      aged 18 to 64 years to examine trends in insurance coverage and uninsurance by
      year, income, and state Medicaid expansion status. We also explored the current
      proportions of veterans with each type of insurance by age group. RESULTS: The
      percentage of veterans with private insurance decreased from 70.8% in 2000 to
      56.9% in 2011, whereas between 2000 and 2016 Department of Veterans Affairs (VA)
      health care coverage (only) almost tripled, Medicaid (without concurrent TRICARE
      or private coverage) doubled, and TRICARE coverage of any type tripled. After
      2011, the percentage of veterans who were uninsured decreased. In 2016, low
      income veterans in Medicaid expansion states had double the Medicaid coverage
      (41.1%) of low-income veterans in nonexpansion states (20.1%). CONCLUSIONS: Our
      estimates, which are nationally representative of noninstitutionalized veterans,
      show marked increases in military-related coverage through TRICARE and VA health
      care. In 2016, only 7.2% of veterans aged 18 to 64 years and 3.7% of all veterans
      (aged 18 years or older) remained uninsured.

PMID- 29345998
TI  - Key Factors Inhibiting Legislative Progress Toward Smoke-Free Coverage in
      Appalachia.
AB  - The Appalachian Region has among the highest rates of smoking and smoking-related
      illness in the United States. Strong smoke-free legislation could help protect
      nonsmoking residents from the harmful effects of secondhand smoke. However, there
      is a dearth of state, county, city, and subcounty smoke-free law coverage
      throughout Appalachia. As of July 2016, only 21% of Appalachian residents were
      covered by comprehensive smoke-free laws (i.e., 100% coverage for workplaces,
      restaurants, and bars). Only 46% of Appalachians lived in places with 100% smoke
      free workplace laws, only 30% lived in places with 100% smoke-free restaurant
      laws, and only 29% lived in places with 100% smoke-free bar laws. Reasons for
      this lack of smoke-free law coverage include socioeconomic disadvantage, the
      historical importance of tobacco in Appalachian economies, and preemptive state
      legislation. By understanding the contextual issues that have inhibited smoke
      free legislation, smoke-free advocates will be better prepared to lead efforts
      that expand smoke-free coverage in this region.

PMID- 29345999
TI  - Cost-Effectiveness of Capping Freeways for Use as Parks: The New York Cross-Bronx
      Expressway Case Study.
AB  - OBJECTIVES: To examine health benefits and cost-effectiveness of implementing a
      freeway deck park to increase urban green space. METHODS: Using the Cross-Bronx
      Expressway in New York City as a case study, we explored the cost-effectiveness
      of implementing deck parks. We built a microsimulation model that included
      increased exercise, fewer accidents, and less pollution as well as the cost of
      implementation and maintenance of the park. We estimated both the quality
      adjusted life years gained and the societal costs for 2017. RESULTS:
      Implementation of a deck park over sunken parts of Cross-Bronx Expressway
      appeared to save both lives and money. Savings were realized for 84% of Monte
      Carlo simulations. CONCLUSIONS: In a rapidly urbanizing world, reclaiming green
      space through deck parks can bring health benefits alongside economic savings
      over the long term. Public Health Implications. Policymakers are seeking ways to
      create cross-sectorial synergies that might improve both quality of urban life
      and health. However, such projects are very expensive, and there is little
      information on their return of investment. Our analysis showed that deck parks
      produce exceptional value when implemented over below-grade sections of road.

PMID- 29346000
TI  - Preventable Emergency Department Visits for Nontraumatic Dental Conditions:
      Trends and Disparities in Nevada, 2009-2015.
AB  - OBJECTIVES: To examine trends and socioeconomic disparities for preventable
      dental-related emergency department (ED) visits in Nevada. METHODS: We pooled
      retrospective data containing 66 267 ED visits involving dental conditions from
      Nevada hospital ED databases from 2009 to 2015. The dependent variable was
      nontraumatic dental conditions identified by International Classification of
      Diseases, Ninth Revision, codes; 3 independent variables included treatment year,
      health insurance status, and race/ethnicity. RESULTS: Odds of ED visits for
      nontraumatic dental conditions increased 16% annually from 2009 to 2015 (odds
      ratio [OR] = 1.16; 95% confidence interval [CI] = 1.13, 1.19). Medicaid (OR =
      2.16; 95% CI = 1.96, 2.39) and uninsured patients (OR = 2.75; 95% CI = 2.52,
      3.00) presenting with nontraumatic dental conditions were 1 to 2 times more
      likely than those with private dental insurance to seek ED treatment. Black
      patients were more likely than White patients to seek ED treatment (OR = 1.13;
      95% CI = 1.02, 1.24). CONCLUSIONS: Socioeconomic and demographic factors were
      significantly associated with ED visits for nontraumatic dental conditions, with
      a steady increase in trends and a widening of socioeconomic disparities in recent
      years.

PMID- 29346001
TI  - Strategies and Challenges in Preventing Violence Against Canadian Indoor Sex
      Workers.
AB  - OBJECTIVES: To examine indoor sex workers' strategies in preventing workplace
      violence and influential socio-structural conditions. METHODS: Data included
      qualitative interviews with 85 sex workers in British Columbia, Canada, from 2014
      through 2016. For analyses, we used interpretive thematic techniques informed by
      World Health Organization position statements on violence. RESULTS: Robbery,
      nonpayment, financial exploitation, and privacy violations were frequent types of
      violence perpetrated by clients, landlords, and neighbors. We identified 2 themes
      that depicted how sex workers prevented violence and mitigated its effects: (1)
      navigating physical spaces and (2) navigating client relationships. CONCLUSIONS:
      Sex workers' diverse strategies to prevent violence and mitigate its effects are
      creative and effective in many circumstances. These are limited, however, by the
      absence of legal and public health regulations governing occupational health and
      safety and stigma associated with sex work. Public Health Implications.
      Occupational health and safety regulatory policies that set conditions for
      clients' substance and condom use within commercial sex transactions are
      required. Revisions to the current legal regulations governing prostitution are
      critical to support optimal work environments that reduce the likelihood of
      violence. These revisions must recognize sex work as a form of labor versus
      victimization.

PMID- 29346003
TI  - Medicaid Expansion and Infant Mortality in the United States.
AB  - OBJECTIVES: To explore the effect of Medicaid expansion on US infant mortality
      rate. METHODS: We examined data from 2010 to 2016 and 2014 to 2016 to compare
      infant mortality rates in states and Washington, DC, that accepted the Affordable
      Care Act Medicaid expansion (Medicaid expansion states) and states that did not
      (non-Medicaid expansion states), stratifying data by race/ethnicity. RESULTS:
      Mean infant mortality rate in non-Medicaid expansion states rose (6.4 to 6.5)
      from 2014 to 2016 but declined in Medicaid expansion states (5.9 to 5.6). Mean
      difference in infant mortality rate in Medicaid expansion versus non-Medicaid
      expansion states increased from 0.573 (P = .08) in 2014 to 0.838 in 2016 (P =
      .006) because of smaller declines in non-Medicaid expansion (11.0%) than in
      Medicaid expansion (15.2%) states. The 14.5% infant mortality rate decline from
      11.7 to 10.0 in African American infants in Medicaid expansion states was more
      than twice that in non-Medicaid expansion states (6.6%: 12.2 to 11.4; P = .012).
      CONCLUSIONS: Infant mortality rate decline was greater in Medicaid expansion
      states, with greater declines among African American infants. Future research
      should explore what aspects of Medicaid expansion may improve infant survival.

PMID- 29346002
TI  - Intermittent Preventive Therapy in Pregnancy and Incidence of Low Birth Weight in
      Malaria-Endemic Countries.
AB  - OBJECTIVES: To estimate the impact of hypothetical antimalarial and nutritional
      interventions (which reduce the prevalence of low midupper arm circumference
      [MUAC]) on the incidence of low birth weight (LBW). METHODS: We analyzed data
      from 14 633 pregnancies from 13 studies conducted across Africa and the Western
      Pacific from 1996 to 2015. We calculated population intervention effects for
      increasing intermittent preventive therapy in pregnancy (IPTp), full coverage
      with bed nets, reduction in malaria infection at delivery, and reductions in the
      prevalence of low MUAC. RESULTS: We estimated that, compared with observed IPTp
      use, administering 3 or more doses of IPTp to all women would decrease the
      incidence of LBW from 9.9% to 6.9% (risk difference = 3.0%; 95% confidence
      interval = 1.7%, 4.0%). The intervention effects for eliminating malaria at
      delivery, increasing bed net ownership, and decreasing low MUAC prevalence were
      all modest. CONCLUSIONS: Increasing IPTp uptake to at least 3 doses could
      decrease the incidence of LBW in malaria-endemic countries. The impact of IPTp on
      LBW was greater than the effect of prevention of malaria, consistent with a
      nonmalarial effect of IPTp, measurement error, or selection bias.

PMID- 29346004
TI  - Universal Lead Screening Requirement: A California Case Study.
AB  - OBJECTIVES: To estimate potential impacts of California Assembly Bill (AB) 1316:
      a requirement for universal screening and insurance coverage for child blood lead
      testing. METHODS: In April 2017 the California Health Benefits Review Program
      (Oakland, CA) analyzed AB 1316 for the California legislature, including a
      systematic review of lead screening effectiveness, commercial insurer surveys
      regarding screening coverage, and actuarial utilization and cost implication
      assessments. RESULTS: Universal screening requirements would increase child lead
      testing by 273%, raise affected populations' premiums by 0.0043%, and detect an
      additional 4777 exposed children 1 year after implementation. CONCLUSIONS: The
      evidence for a net societal benefit of universal screening approach is limited
      and is not supported by prominent medical professional groups. Public Health
      Implications. California expanded targeted screening to identify additional
      children at higher risk for lead poisoning on the basis of California-specific
      risk factors, while mitigating the potential harms of universal screening such as
      an increase in false positive tests and health care costs.

PMID- 29346005
TI  - Ethical Issues in Social Media Research for Public Health.
AB  - Social media (SM) offer huge potential for public health research, serving as a
      vehicle for surveillance, delivery of health interventions, recruitment to
      trials, collection of data, and dissemination. However, the networked nature of
      the data means they are riddled with ethical challenges, and no clear consensus
      has emerged as to the ethical handling of such data. This article outlines the
      key ethical concerns for public health researchers using SM and discusses how
      these concerns might best be addressed. Key issues discussed include privacy;
      anonymity and confidentiality; authenticity; the rapidly changing SM environment;
      informed consent; recruitment, voluntary participation, and sampling; minimizing
      harm; and data security and management. Despite the obvious need, producing a set
      of prescriptive guidelines for researchers using SM is difficult because the
      field is evolving quickly. What is clear, however, is that the ethical issues
      connected to SM-related public health research are also growing. Most
      importantly, public health researchers must work within the ethical principles
      set out by the Declaration of Helsinki that protect individual users first and
      foremost.

PMID- 29346006
TI  - Public Health Education: Teaching Epidemiology in High School Classrooms.
AB  - Epidemiology instruction has expanded at the undergraduate level in part because
      it increases student critical thinking and scientific literacy, promotes
      students' perception of public health as both practical and relevant, and
      empowers students as independent, lifelong learners. Why then are more high
      schools not adopting epidemiology as a course requirement for students? Although
      prior iterations of high school epidemiology courses are noteworthy for
      incorporating active and participatory learning, embedding them into existing and
      continually shifting curricula is challenging and time-consuming, especially for
      teachers not trained in the field. It also may be argued that currently available
      epidemiology teaching resources emphasize content rather than thinking skills and
      therefore do not optimally promote students' personal engagement with, and in
      depth understanding of, the mission and goals of public health. I propose a new
      framework for high school epidemiology that draws from progressive education
      ideology, including three critical elements: empowerment, authenticity, and
      transfer. I provide multiple examples to show how this framework has been used
      across a wide array of settings to hone epidemiology thinking skills in high
      school students.

PMID- 29346007
TI  - The Rise and Fall of "Universal Health Coverage" as a Goal of International
      Health Politics, 1925-1952.
AB  - The UN Sustainable Development Goals of 2015 have restored universal health
      coverage (UHC) to prominence in the international health agenda. Can
      understanding the past illuminate the prospects for UHC in the present? This
      article traces an earlier history of UHC as an objective of international health
      politics. Its focus is the efforts of the International Labor Organization (ILO),
      whose Philadelphia Declaration (1944) announced the goal of universal social
      security, including medical coverage and care. After World War II, the ILO
      attempted to enshrine this in an international convention, which nation states
      would ratify. However, by 1952 these efforts had failed, and the final convention
      was so diluted that universalism was unobtainable. Our analysis first explains
      the consolidation of ideas about social security and health care, tracing
      transnational policy linkages among experts whose world view transcended narrow
      loyalties. We then show how UHC goals became marginalized, through the opposition
      of employers and organized medicine, and of certain nation states, both rich and
      poor. We conclude with reflections on how these findings might help us in
      thinking about the challenges of advancing UHC today.

PMID- 29346008
TI  - Follow-Up Care Provider Preferences of Adolescent and Young Adult Cancer
      Survivors.
AB  - PURPOSE: To explore the experiences and perspectives of adolescent and young
      adult (AYA) cancer survivors regarding patient-provider relationships and their
      preferences surrounding type of healthcare provider for follow-up care. METHODS:
      We recruited AYA cancer survivors who were diagnosed between the ages of 15 and
      39 using the Utah Cancer Registry. Twenty-eight survivors participated in six
      focus groups held between March and May of 2015 in Salt Lake City and St. George,
      Utah. This analysis focuses on how survivors' preferences about type of
      healthcare provider may influence their transition into, and utilization of,
      follow-up care. RESULTS: On average, survivors were 6.3 (standard deviation =
      1.7) years from their cancer diagnosis. A majority of survivors expressed a
      desire not to transition to a new provider and preferred continuing to see their
      oncologist for follow-up care. For these survivors, this was due to already
      having a close relationship with their oncologist and because they trusted their
      provider's knowledge about cancer and how to handle late effects. However,
      survivors placed emphasis on being comfortable with their healthcare provider,
      regardless of provider type. CONCLUSIONS: Our findings demonstrate the importance
      of formalizing provider transitions and roles after cancer therapy to improve
      patient comfort with new providers. By understanding the complexities of the
      transition from active cancer treatment to follow-up care for AYA survivors,
      these findings can inform programs undertaking post-care educational activities
      to ensure a seamless transition into survivorship care. Survivorship care plans
      can facilitate these transitions and improve patient confidence in follow-up
      care.

PMID- 29346009
TI  - Automation on an Open-Access Platform of Alzheimer's Disease Biomarker
      Immunoassays.
AB  - The lack of (inter-)laboratory standardization has hampered the application of
      universal cutoff values for Alzheimer's disease (AD) cerebrospinal fluid (CSF)
      biomarkers and their transfer to general clinical practice. The automation of the
      AD biomarker immunoassays is suggested to generate more robust results than using
      manual testing. Open-access platforms will facilitate the integration of
      automation for novel biomarkers, allowing the introduction of the protein
      profiling concept. A feasibility study was performed on an automated open-access
      platform of the commercial immunoassays for the 42-amino-acid isoform of amyloid
      beta (Abeta1-42), Abeta1-40, and total tau in CSF. Automated Abeta1-42, Abeta1
      40, and tau immunoassays were performed within predefined acceptance criteria for
      bias and imprecision. Similar accuracy was obtained for ready-to-use calibrators
      as for reconstituted lyophilized kit calibrators. When compared with the addition
      of a standard curve in each test run, the use of a master calibrator curve,
      determined before and applied to each batch analysis as the standard curve,
      yielded an acceptable overall bias of -2.6% and -0.9% for Abeta1-42 and Abeta1
      40, respectively, with an imprecision profile of 6.2% and 8.4%, respectively. Our
      findings show that transfer of commercial manual immunoassays to fully automated
      open-access platforms is feasible, as it performs according to universal
      acceptance criteria.

PMID- 29346010
TI  - Identification and Correction of Additive and Multiplicative Spatial Biases in
      Experimental High-Throughput Screening.
AB  - Data generated by high-throughput screening (HTS) technologies are prone to
      spatial bias. Traditionally, bias correction methods used in HTS assume either a
      simple additive or, more recently, a simple multiplicative spatial bias model.
      These models do not, however, always provide an accurate correction of
      measurements in wells located at the intersection of rows and columns affected by
      spatial bias. The measurements in these wells depend on the nature of interaction
      between the involved biases. Here, we propose two novel additive and two novel
      multiplicative spatial bias models accounting for different types of bias
      interactions. We describe a statistical procedure that allows for detecting and
      removing different types of additive and multiplicative spatial biases from
      multiwell plates. We show how this procedure can be applied by analyzing data
      generated by the four HTS technologies (homogeneous, microorganism, cell-based,
      and gene expression HTS), the three high-content screening (HCS) technologies
      (area, intensity, and cell-count HCS), and the only small-molecule microarray
      technology available in the ChemBank small-molecule screening database. The
      proposed methods are included in the AssayCorrector program, implemented in R,
      and available on CRAN.

PMID- 29346011
TI  - Minimally Invasive Management of Severe Aortoiliac Occlusive Disease.
AB  - BACKGROUND: Peripheral arterial disease (PAD) is a complex and highly prevalent
      pathology. It has been estimated that ~8.5 million people in the United States
      are affected by PAD, of which 12%-20% are older than age 60. The TransAtlantic
      Inter-Society Consensus (TASC) guidelines classified aortoiliac atherosclerotic
      disease based on morphology and level of lesions. TASC II guidelines recommend
      bilateral surgical bypass to the femoral arteries for TASC II C and D lesions.
      The aortobifemoral bypass (ABF) has been considered the gold standard in the
      treatment of aortoiliac occlusive disease (AIOD). The long-term patency rate of
      85%-90% at 5 years and 75%-80% at 10 years has been for a long time unmatched by
      other methods of revascularization. METHODS: This is a review of the current
      literature regarding minimally invasive strategies in the care of TASC II C and D
      aortoiliac disease. RESULTS: Endovascular therapies have led to a paradigm change
      even in the treatment of highly advanced lesions. Reconstruction of the aortic
      bifurcation for distal aortic and/or ostial unilateral/bilateral common iliac
      artery disease can be achieved via the deployment of stents with "kissing"
      technique and aortic endografts. Laparoscopic aortoiliac surgery for TASC II C
      and D lesions was first proposed in 1993. Total laparoscopic, laparoscopic
      assisted, and laparobotic techniques have been described. Minimal incision aortic
      surgery (MIAS) describes abdominal incisions varying from 6 to 12 cm and
      positional adjustment of retractors to access the retroperitoneum for infrarenal
      aortic aneurysms and/or AIOD. CONCLUSIONS: Although initial enthusiasm
      laparoscopic aortic surgery and MIAS have failed to gain acceptance in the
      vascular surgery community due to intrinsic procedural challenges, they are
      currently practiced in few highly specialized centers. At this moment, high
      quality evidence is lacking regarding the further feasibility of these techniques
      and their applicability in general practice compared to endovascular therapies.
      While the ABF remains still the optimal choice in select, fit for surgery
      patients, endovascular therapies offer a less invasive approach that may provide
      a mortality and morbidity benefit in higher risk patients with acceptable short-
      and long-term outcomes.

PMID- 29346012
TI  - The Combination of Probiotic Complex, Rosavin, and Zinc Improves Pain and
      Cartilage Destruction in an Osteoarthritis Rat Model.
AB  - Osteoarthritis (OA), a degenerative disorder, induces pain, joint inflammation,
      and destruction of the articular cartilage matrix. Probiotic complex, rosavin,
      and zinc have been used as dietary supplements that exhibit anti-inflammatory and
      antioxidant properties. However, there is no evidence demonstrating a synergic
      effect in OA. This study aims to determine whether combination with probiotic
      complex, rosavin, and zinc decreases progression of monosodium iodoacetate (MIA)
      induced OA rat model. The combination improved pain levels by preventing
      cartilage damage. The expression of proinflammatory cytokines and catabolic
      factors was reduced by the combination within the joint tissue. However, the
      combination increased anti-inflammatory cytokines as well as the anabolic factor
      production. The gene level of catabolic factors was decreased with treatment of
      the combination in chondrocytes isolated from OA patients. These results suggest
      that the combination can improve MIA development through the inhibition of
      proinflammatory cytokines and cartilage destruction, thus playing a key role as a
      therapeutic candidate for OA treatment.

PMID- 29346013
TI  - Purification of Lymphocytes by Acoustic Separation in Plastic Microchannels.
AB  - Emerging cell therapies have created new demands for instruments that will
      increase processing efficiency. Purification of lymphocytes prior to downstream
      steps of gene transfer currently relies on centrifugal separation, which has
      drawbacks in output sample purity and process automation. Here, we present an
      alternative approach to blood cell purification using acoustic forces in plastic
      microchannels. We provide details regarding the system's ability to purify
      lymphocytes relative to other blood cell types while maintaining a high overall
      recovery, testing performance starting from leukapheresis product, buffy coat,
      and whole blood. Depending on settings, the device achieves for lymphocytes up to
      97% purity and up to 68% recovery, and depletes 98% of monocytes while also
      reducing red cells and platelets. We expect that future scale-up of our system
      for increased throughput will enable its incorporation in the cell therapy
      workflow, and that it could ultimately reduce costs and expand access for
      patients.

PMID- 29346014
TI  - Role of the Lymphatic System in the Pathogenesis of Hypertension in Humans.
AB  - BACKGROUND: Recent studies, mainly on animal models, have suggested that
      negatively charged glycosaminoglycans, macrophages, and lymph vessels in the skin
      interstitium may serve as extrarenal control of sodium balance and blood
      pressure. The aim of the study was to prove the hypothesis that skin interstitium
      has a role in the pathogenesis of hypertension in humans. METHODS AND RESULTS: We
      have examined skin biopsies in 91 patients from the department of surgery who had
      elective surgery with abdominal skin incision: 43 were hypertensive, 14 had
      resistant hypertension, and 34 with normal blood pressure as control group
      (median patients' age in these groups estimated accordingly 64 vs. 64 vs. 61.5; p
      > 0.05). We have studied (1) the content of Na+, water, accumulation of
      macrophages (CD68), and density of lymphatic vessels (D2-40) and blood vessels
      (CD31) in the specimens of abdominal skin taken at the time of surgery and (2)
      plasma NT-proANP, vascular endothelial growth factor (VEGF)-C, and VEGF-D
      concentrations. The study groups differed in skin expression of CD68 (control vs.
      hypertension vs. resistant hypertension groups were accordingly: 3.33 vs. 4.00
      vs. 8.33; p = 0.005) and in serum concentration of VEGF-C (5792 vs. 4348 vs. 3974
      pg/mL; p = 0.026). Differences among groups in plasma NT-proANP levels were close
      to statistical significance (p = 0.056). CONCLUSIONS: Our results confirm that
      skin interstitium may be involved in the pathogenesis of essential hypertension
      in humans. Lower levels of VEGF-C in hypertensive groups suggest that impairment
      of lymphangiogenesis and protective function of the skin lymphatic system may
      play a role in the pathogenesis of hypertension.

PMID- 29346015
TI  - Treatment of a textile effluent by adsorption with cork granules and titanium
      dioxide nanomaterial.
AB  - This study aimed to explore the efficiency of two adsorbents, cork granules with
      different granulometry and titanium dioxide nanomaterial, in the removal of
      chemical oxygen demand (COD), colour and toxicity from a textile effluent. The
      adsorption assays with cork were unsatisfactory in the removal of chemical
      parameters however they eliminated the acute toxicity of the raw effluent to
      Daphnia magna. The assay with TiO2 NM did not prove to be efficient in the
      removal of colour and COD even after 240 min of contact; nevertheless it also
      reduced the raw effluent toxicity. The best approach for complete remediation of
      the textile effluent has not yet been found however promising findings were
      achieved, which may be an asset in future adsorption assays.

PMID- 29346016
TI  - In situ electrochemical manipulation of oxidation-reduction potential in
      saturated subsurface matrices.
AB  - Application of a low-intensity electric field is known to influence oxidation
      reduction (redox) potential in a saturated matrix. In this study, such redox
      manipulation was attempted in at a site with contaminated aquifer. At the
      experiment field site, electrodes connected to a direct current (DC) source
      provided an electric field with an intensity of 1.82 V m-1. Redox potentials at
      locations 3.0 m and 7.9 m from the cathode decreased by 111 mV and 33 mV within a
      few hours, respectively, indicating that reducing conditions in the aquifer may
      be established within the electric field. Overall, it is possible to manipulate
      in situ redox potential in saturated subsurface matrices by applying low
      intensity electric fields.

PMID- 29346017
TI  - The Role of Posterior Parietal Cortex in Beat-based Timing Perception: A
      Continuous Theta Burst Stimulation Study.
AB  - There is growing interest in how the brain's motor systems contribute to the
      perception of musical rhythms. The Action Simulation for Auditory Prediction
      hypothesis proposes that the dorsal auditory stream is involved in bidirectional
      interchange between auditory perception and beat-based prediction in motor
      planning structures via parietal cortex [Patel, A. D., & Iversen, J. R. The
      evolutionary neuroscience of musical beat perception: The Action Simulation for
      Auditory Prediction (ASAP) hypothesis. Frontiers in Systems Neuroscience, 8, 57,
      2014]. We used a TMS protocol, continuous theta burst stimulation (cTBS), that is
      known to down-regulate cortical activity for up to 60 min following stimulation
      to test for causal contributions to beat-based timing perception. cTBS target
      areas included the left posterior parietal cortex (lPPC), which is part of the
      dorsal auditory stream, and the left SMA (lSMA). We hypothesized that down
      regulating lPPC would interfere with accurate beat-based perception by disrupting
      the dorsal auditory stream. We hypothesized that we would induce no interference
      to absolute timing ability. We predicted that down-regulating lSMA, which is not
      part of the dorsal auditory stream but has been implicated in internally timed
      movements, would also interfere with accurate beat-based timing perception. We
      show ( n = 25) that cTBS down-regulation of lPPC does interfere with beat-based
      timing ability, but only the ability to detect shifts in beat phase, not changes
      in tempo. Down-regulation of lSMA, in contrast, did not interfere with beat-based
      timing. As expected, absolute interval timing ability was not impacted by the
      down-regulation of lPPC or lSMA. These results support that the dorsal auditory
      stream plays an essential role in accurate phase perception in beat-based timing.
      We find no evidence of an essential role of parietal cortex or SMA in interval
      timing.

PMID- 29346018
TI  - The Tortoise and the Hare: Interactions between Reinforcement Learning and
      Working Memory.
AB  - Learning to make rewarding choices in response to stimuli depends on a slow but
      steady process, reinforcement learning, and a fast and flexible, but capacity
      limited process, working memory. Using both systems in parallel, with their
      contributions weighted based on performance, should allow us to leverage the best
      of each system: rapid early learning, supplemented by long-term robust
      acquisition. However, this assumes that using one process does not interfere with
      the other. We use computational modeling to investigate the interactions between
      the two processes in a behavioral experiment and show that working memory
      interferes with reinforcement learning. Previous research showed that neural
      representations of reward prediction errors, a key marker of reinforcement
      learning, were blunted when working memory was used for learning. We thus
      predicted that arbitrating in favor of working memory to learn faster in simple
      problems would weaken the reinforcement learning process. We tested this by
      measuring performance in a delayed testing phase where the use of working memory
      was impossible, and thus participant choices depended on reinforcement learning.
      Counterintuitively, but confirming our predictions, we observed that associations
      learned most easily were retained worse than associations learned slower: Using
      working memory to learn quickly came at the cost of long-term retention.
      Computational modeling confirmed that this could only be accounted for by working
      memory interference in reinforcement learning computations. These results further
      our understanding of how multiple systems contribute in parallel to human
      learning and may have important applications for education and computational
      psychiatry.

PMID- 29346019
TI  - Independent Attention Mechanisms Control the Activation of Tactile and Visual
      Working Memory Representations.
AB  - Working memory (WM) is limited in capacity, but it is controversial whether these
      capacity limitations are domain-general or are generated independently within
      separate modality-specific memory systems. These alternative accounts were tested
      in bimodal visual/tactile WM tasks. In Experiment 1, participants memorized the
      locations of simultaneously presented task-relevant visual and tactile stimuli.
      Visual and tactile WM load was manipulated independently (one, two, or three
      items per modality), and one modality was unpredictably tested after each trial.
      To track the activation of visual and tactile WM representations during the
      retention interval, the visual contralateral delay activity (CDA) and tactile CDA
      (tCDA) were measured over visual and somatosensory cortex, respectively. CDA and
      tCDA amplitudes were selectively affected by WM load in the corresponding
      (tactile or visual) modality. The CDA parametrically increased when visual load
      increased from one to two and to three items. The tCDA was enhanced when tactile
      load increased from one to two items and showed no further enhancement for three
      tactile items. Critically, these load effects were strictly modality-specific, as
      substantiated by Bayesian statistics. Increasing tactile load did not affect the
      visual CDA, and increasing visual load did not modulate the tCDA. Task
      performance at memory test was also unaffected by WM load in the other (untested)
      modality. This was confirmed in a second behavioral experiment where tactile and
      visual loads were either two or four items, unimodal baseline conditions were
      included, and participants performed a color change detection task in the visual
      modality. These results show that WM capacity is not limited by a domain-general
      mechanism that operates across sensory modalities. They suggest instead that WM
      storage is mediated by distributed modality-specific control mechanisms that are
      activated independently and in parallel during multisensory WM.

PMID- 29346020
TI  - Sequential Ridge Augmentation Protocol for Hard and Soft Tissue Grafting in
      Alveolar Ridge Deficiencies: A Proposed Evidence-Based Algorithm.

PMID- 29346021
TI  - Extending Implications of Study Findings on Real-World Implementation.

PMID- 29346022
TI  - The Road From Theory to Reality: Illuminating the Complexity of Prospective
      Cancer Bundles.

PMID- 29346023
TI  - Fertility Preservation in Pediatric Oncology Patients: New Perspectives.
AB  - Over the past 30 years, advances in antineoplastic treatment led to a significant
      increase in the survival of patients with childhood cancer. In Europe and the
      United States, 82% of children, adolescents, and young adults survive 5 years
      from the cancer diagnosis and the majority achieves long-term survival into
      adulthood. The impact of cancer therapy on fertility is related to the age of the
      patient and to the duration, dose/intensity, and type of treatment. Exposure to
      chemotherapy or to radiation to gonads or pituitary brings long-term
      complications of cancer-directed therapies that include effects on reproductive
      capacity. Different methods to preserve fertility can be offered. In prepubertal
      women, ovarian tissue freezing, in vitro maturation, and surgical movement of
      ovaries outside the field of irradiation are still experimental. In pubertal and
      postpubertal women, oocyte-embryo freezing is an established option. In men, the
      options are sperm cryopreservation, gonadal transposition, and testicular tissue
      or spermatogonial cryopreservation and reimplantation. Fertility risks and
      provision of strategies to minimize cancer treatment impact fertility include
      discussion of the tail of the option before cancer treatment. Having to make a
      decision in a limited time, while still coming to terms with a potentially life
      threatening diagnosis, can cause patients to feel overwhelmed. To date, there are
      no uniform guidelines on how to approach this problem, so it is important to be
      aware of it for proper clinical practice.

PMID- 29346024
TI  - Occurrence of polycyclic aromatic hydrocarbons in surface water and hospital
      wastewater.
AB  - The main objective of this study was to determine the occurrence of polycyclic
      aromatic hydrocarbons (PAHs) in surface water samples collected from different
      points along the stream that flows through the Campus of the Federal University
      of Santa Maria, RS-Brazil. Before reaching the campus, the water in the stream is
      already contaminated by wastewater discharged from the surrounding, and once
      inside the Campus, additional wastewater from a Gas Station situated close to the
      University hospital. A bench scale photodegradation experiment was conducted of
      the occurring traces of anthracene, phenanthrene and naphthalene, with the aid of
      a stirred tank reactor and polymer-supported TiO2 as a catalyst. To prevent loss
      of the low soluble analytes, it was necessary to add 5% and 10% acetonitrile, as
      an organic modifier of the synthetic aqueous solutions and real samples,
      respectively. An experimental design was employed and the best conditions for the
      photocatalysis of the aqueous solutions and real samples were pH 9 and pH 7, and
      35 degrees C and 30 degrees C, respectively. Under optimized conditions, the
      analytes were completely degraded after 60 min of irradiation. The subproducts of
      the photocatalysis were identified through gas chromatography/mass spectrometry,
      and fragmentation routes were proposed. The mean concentrations of PAHs in the
      polluted surface water and hospital wastewater were relatively high: 3.9 +/- 1.7
      and 21.5 +/- 2.8 ug L-1, respectively. A preliminary risk assessment revealed
      that the presence of anthracene requires particular attention. The risk posed by
      the occurrence of PAHs in the surface water and hospital wastewater samples
      confirms the need for an efficient treatment system.

PMID- 29346025
TI  - Linkage of Metabolic Defects to Activated PIK3CA Alleles in Endothelial Cells
      Derived from Lymphatic Malformation.
AB  - BACKGROUND: Lymphatic endothelial cells (LECs) derived from lymphatic
      malformations (LMs) bear activated PIK3CA alleles yet display an inflammatory
      gene expression profile. A basis for the inflammatory phenotype was sought by
      screening for coexisting somatic mutations. METHODS AND RESULTS: Fourteen
      independent LEC populations bearing activated PIK3CA alleles were isolated from
      LM. These were characterized by the expression of growth and inflammatory genes
      (VEGFC, IL-6, COX-2, IL-8, HO-1, E-SEL) by qRT-PCR. Most commonly upregulated
      gene products were VEGFC, COX2, HO-1, and ANGPTL4. The specific inhibition of
      PI3K reduced VEGFC expression without resolving inflammation. Whole exome
      sequencing of six LM-LEC populations identified five novel somatically acquired
      alleles coexisting with activated PIK3CA alleles. Two affected genes regulate
      lipid droplet metabolism (FITM2 and ATG2A), two are gene regulators (MTA1 and
      TAF1L), and the fifth is an isoform of ANK3 (an endosomal/lysosomal protein).
      Inhibition of AMPK implicated its involvement in regulating COX-2 and HO-1
      overexpression. ANGPTL4 expression was independent of AMPK and PI3K activity and
      reflected lipid stress demonstrated in normal LECs. AMPK activation with AICAR
      had a selective growth-limiting effect in a subset of LM-LEC isolates.
      CONCLUSIONS: Inflammatory stress displayed by LM-LECs is consistent with errors
      in lipid metabolism that may be linked to acquired mutations. The acquisition of
      PIK3CA alleles may be a permissive event that antagonizes inflammation and
      metabolic defect.

PMID- 29346026
TI  - A Scintigraphic Method for Quantitation of Lymphatic Function in Arm Lymphedema.
AB  - BACKGROUND: Lymphoscintigraphy is commonly used to assess breast cancer-related
      lymphedema. However, a reliable quantitative method that clearly distinguishes
      normal lymphatic function from lymphedema is desired. We propose a quantitative
      method based upon the physiological mean transit time (MTT) measure of lymph
      fluid passing through the arm. METHODS AND RESULTS: Eleven patients, aged 34-68
      years, with unilateral arm lymphedema following breast cancer treatment underwent
      simultaneous bilateral lymphoscintigraphy using intradermal injection of 99mTc
      labeled human serum albumin (HSA). Imaging was performed at 30-45 minute
      intervals for 5 hours. Time activity curves from each injection site and each arm
      region were recorded. The input into the arm region was obtained as the (minus)
      time derivative of the injection site activity curve. In the proposed model the
      arm activity curve was considered to arise from the convolution of the retention
      function and the input function. The retention function was obtained by fitting
      the calculated arm activity curve to the measured arm activity curve. The MTT of
      activity passing through the arm was calculated as the time integral of the
      resulting retention function. All measured time activity curves were well
      described by the model. The MTT of the lymphedema arm (mean 60.1 minutes, range
      22-105 minutes) was markedly different from that of the contralateral normal arm
      (mean 5.4 minutes, range 1.2-8.7 minutes), p < 0.0001. CONCLUSION: The proposed
      model showed great similarity with measured time activity curves and was capable
      of quantitatively distinguishing lymphatic function of the lymphedema arm from
      that of the normal arm in terms of calculated MTT.

PMID- 29346027
TI  - Postsurgical Outcomes and Surgical Completeness of Robotic Thyroid Surgery: A
      Single Surgeon's Experience on 700 Cases.
AB  - BACKGROUND: Advanced technology and understanding of robotic surgical system have
      rendered robotic thyroid surgery more expanding. The aim of this study was to
      identify the periodic changes in postsurgical outcomes of robotic thyroid surgery
      performed by a single surgeon. METHODS: We conducted a retrospective review of
      700 robotic thyroid surgery cases using gasless trans-axillary approach. RESULTS:
      All patients underwent successful operations without conversion to open surgery,
      and were mostly younger than 45 years, female, less-extended thyroid surgery and
      lymph node dissection, and thyroid cancer. The median follow-up period was 67
      months (12-99 months). Regarding technical outcomes, the operation time declined
      steeply after 100 consecutive cases, and reached 120.0-132.7 minutes for thyroid
      lobectomy and 162.9-174.1 minutes for total thyroidectomy (TT). The most common
      complication was transient hypoparathyroidism (43.7%), whose incidence decreased
      steeply to a range of 9.1% to 25.0% after 300 consecutive cases. Regarding
      surgical completeness for thyroid cancer, an average of seven lymph nodes was
      retrieved through central compartment node dissection without fluctuation over
      time. The proportion of the patients with serum stimulated thyroglobulin levels
      <10 ng/mL at the time of radioactive iodine remnant ablation after TT and <1
      ng/mL 6-12 months after the first remnant ablation ranged between 86.4%-100% and
      66.7%-100%, respectively, without significant fluctuation. CONCLUSION: For
      properly selected patients, robotic thyroid surgery is useful surgical option
      with reliable technical outcome and surgical completeness and cosmetic benefit.

PMID- 29346029
TI  - Unifying Visual Space Across the Left and Right Hemifields.
AB  - Visual space is perceived as continuous and stable even though visual inputs from
      the left and right visual fields are initially processed separately within the
      two cortical hemispheres. In the research reported here, we examined whether the
      visual system utilizes a dynamic recalibration mechanism to integrate these
      representations and to maintain alignment across the visual fields. Subjects
      adapted to randomly oriented moving lines that straddled the vertical meridian;
      these lines were vertically offset between the left and right hemifields.
      Subsequent vernier alignment judgments revealed a negative aftereffect: An offset
      in the same direction as the adaptation was required to correct the perceived
      misalignment. This aftereffect was specific to adaptation to vertical, but not
      horizontal, misalignments and also occurred following adaptation to movie clips
      and patterns without coherent motion. Our results demonstrate that the visual
      system unifies the left and right halves of visual space by continuously
      recalibrating the alignment of elements across the visual fields.

PMID- 29346030
TI  - The Challenge of Surgical Sepsis.

PMID- 29346031
TI  - 2016 New Horizons Lecture: Beyond Imaging-Radiology of Tomorrow.
AB  - This article is based on the New Horizons lecture delivered at the 2016
      Radiological Society of North America Annual Meeting. It addresses looming
      changes for radiology, many of which stem from the disruptive effects of the
      Fourth Industrial Revolution. This is an emerging era of unprecedented rapid
      innovation marked by the integration of diverse disciplines and technologies,
      including data science, machine learning, and artificial intelligence
      technologies that narrow the gap between man and machine. Technologic advances
      and the convergence of life sciences, physical sciences, and bioengineering are
      creating extraordinary opportunities in diagnostic radiology, image-guided
      therapy, targeted radionuclide therapy, and radiology informatics, including
      radiologic image analysis. This article uses the example of oncology to make the
      case that, if members in the field of radiology continue to be innovative and
      continuously reinvent themselves, radiology can play an ever-increasing role in
      both precision medicine and value-driven health care. (c) RSNA, 2018.

PMID- 29346032
TI  - Pathways Into Literacy: The Role of Early Oral Language Abilities and Family Risk
      for Dyslexia.
AB  - The present study investigated the role of early oral language and family risk
      for dyslexia in the two developmental pathways toward reading comprehension,
      through word reading and through oral language abilities. The sample contained
      237 children (164 at family risk for dyslexia) from the Dutch Dyslexia Program.
      Longitudinal data were obtained on seven occasions when children were between 4
      and 12 years old. The relationship between early oral language ability and
      reading comprehension at the age of 12 years was mediated by preliteracy skills
      and word-decoding ability for the first pathway and by later language abilities
      for the second pathway. Family risk influenced literacy development through its
      subsequent relations with preliteracy skills, word decoding, and reading
      comprehension. Although performance on language measures was often lower for the
      family-risk group than for the no-family-risk group, family risk did not have a
      specific relation with either early or later oral language abilities.

PMID- 29346033
TI  - The psychology of elite cycling: a systematic review.
AB  - This systematic review sought to synthesise what is currently known about the
      psychology of elite cycling. Nine electronic databases were searched in March
      2017 for studies reporting an empirical test of any psychological construct in an
      elite cycling sample. Fourteen studies (total n = 427) met inclusion criteria.
      Eight studies were coded as having high risk of bias. Themes extracted included
      mood, anxiety, self-confidence, pain, and cognitive function. Few studies had
      similar objectives meaning that in many instances findings could not be
      synthesised in a meaningful way. Nevertheless, there was some cross-study
      evidence that elite cyclists have more positive mood states (relative to
      normative scores), pre-race anxiety impairs performance (among male cyclists),
      and associative strategies are perceived as helpful for pain management. Among
      single studies coded as having low risk of bias, evidence suggests that implicit
      beliefs affect decision making performance, elite cyclists are less susceptible
      to mental fatigue (than non-elite cyclists), and better leadership skills relates
      to greater social labouring. Limitations include non-standardisation of measures,
      lack of follow-up data, small sample sizes, and overall poor research quality.
      The findings of this systematic review might be used to inform research and
      theory development on the psychology of elite endurance cycling.

PMID- 29346034
TI  - Coagulopathy in Severe Sepsis: Interconnectivity of Coagulation and the Immune
      System.
AB  - BACKGROUND: Disseminated intravascular coagulation (DIC) remains a challenging
      complication of infection with inadequate treatment and significant morbidity and
      mortality rates. METHODS: Review of the English-language literature. RESULTS:
      Disseminated intravascular coagulation arises from the immune system's response
      to microbial invasion, as well as the byproducts of cell death that result from
      severe sepsis. This response triggers the coagulation system through an
      interconnected network of cellular and molecular signals, which developed
      originally as an evolutionary mechanism intended to isolate micro-organisms via
      fibrin mesh formation. However, this response has untoward consequences,
      including hemorrhage and thrombosis caused by dysregulation of the coagulation
      cascade and fibrinolysis system. Ultimately, diagnosis relies on clinical
      findings and laboratory studies that recognize excessive activation of the
      coagulation system, and treatment focuses on supportive measures and correction
      of coagulation abnormalities. Clinically, DIC secondary to sepsis in the surgical
      population presents a challenge both in diagnosis and in treatment. Biologically,
      however, DIC epitomizes the crosstalk between signaling pathways that is
      essential to normal physiology, while demonstrating the devastating consequences
      when failure of local control results in systemic derangements. CONCLUSIONS: This
      paper discusses the pathophysiology of coagulopathy and fibrinolysis secondary to
      sepsis, the diagnostic tools available to identify the abnormalities, and the
      available treatments.

PMID- 29346035
TI  - Determination of 105 antibiotic, anti-inflammatory, antiparasitic agents and
      tranquilizers by LC-MS/MS based on an acidic QuEChERS-like extraction.
AB  - A procedure for screening 105 veterinary drugs in foods by liquid chromatography
      tandem mass-spectrometry (LC-MS/MS) is presented. Its scope encompasses raw
      materials of animal origin (milk, meat, fish, egg and fat) but also related
      processed ingredients and finished products commonly used and manufactured by
      food business operators. Due to the complexity of the matrices considered and to
      efficiently deal with losses during extraction and matrix effects during MS
      source ionisation, each sample was analysed twice, that is 'unspiked' and 'spiked
      at the screening target concentration' using a QuEChERS-like extraction. The
      entire procedure was validated according to the European Community Reference
      Laboratories Residues Guidelines. False-negative and false-positive rates were
      below 5% for all veterinary drugs whatever the food matrix. Effectiveness of the
      procedure was further demonstrated through participation to five proficiency
      tests and its ruggedness demonstrated in quality control operations by a second
      laboratory.

PMID- 29346036
TI  - Genetics, the Rearing Environment, and the Intergenerational Transmission of
      Divorce: A Swedish National Adoption Study.
AB  - We used classical and extended adoption designs in Swedish registries to
      disentangle genetic and rearing-environment influences on the intergenerational
      transmission of divorce. In classical adoption analyses, adoptees ( n = 19,715)
      resembled their biological parents, rather than their adoptive parents, in their
      history of divorce. In extended adoption analyses, offspring ( n = 82,698)
      resembled their not-lived-with fathers and their lived-with mothers. There was
      stronger resemblance to lived-with mothers, providing indirect evidence of
      rearing-environment influences on the intergenerational transmission of divorce.
      The heritability of divorce assessed across generations was 0.13. We attempted to
      replicate our findings using within-generation data from adoptive and biological
      siblings ( ns = 8,523-53,097). Adoptees resembled their biological, not adoptive,
      siblings in their history of divorce. Thus, there was consistent evidence that
      genetic factors contributed to the intergenerational transmission of divorce but
      weaker evidence for a rearing-environment effect of divorce. Within-generation
      data from siblings supported these conclusions.

PMID- 29346037
TI  - Development of an ultrasensitive PCR assay for polycyclic musk determination in
      fish.
AB  - Polycyclic musks (PCMs) in the aquatic environment and organisms have become an
      emerging environmental issue because of their potential risk. The most used
      method for polycyclic musk determination is gas chromatography-mass spectrometry
      (GC-MS) with different sample extractions, which are somewhat expensive to
      operate, complex and laborious. In this study, a novel and ultrasensitive real
      time polymerase chain reaction (PCR) assay with multiple signal amplification of
      carboxylic-DNA by gold nanoparticle-polyamidoamine conjugation (Au-PAMAM) was
      developed for determining polycyclic musks in fish. Hapten and immunogen were
      specially prepared. Polyclonal antibodies were produced based on the optimal
      immunisation, and the antibodies were characterised. Due to PAMAM's unique
      nanostructure of numerous functional amino groups, polyclonal antibody and
      carboxylic-DNA were immobilised by Au-PAMAM conjugation to develop the antibody
      Au-PAMAM-DNA probes, which were used as a signal DNA amplifier in the PCR system.
      Compared with real-time immuno-PCR, this biological probe-amplified immuno-PCR
      (BPAI-PCR) assay had higher sensitivity due to the probes' higher ratio of signal
      DNA. Finally, the BPAI-PCR assay was applied to analyse AHTN (7-acetyl
      1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene,Tonalide) concentrations in
      fish samples in the range from 1 pg/L to 10 ng/L, giving an of LOD 0.61 pg/L. In
      general, due to the specificity of the antibody and novel nanoprobe design, this
      BPAI-PCR assay provided a potential way for trace analysis of AHTN in the aquatic
      organisms. The high concentrations of AHTN found in cultivated fish should
      encourage further toxicological studies.

PMID- 29346038
TI  - Smartphone Applications for Amblyopia Treatment: A Review of Current Apps and
      Professional Involvement.
AB  - OBJECTIVES: The objective of this study was to review games for amblyopia (lazy
      eye) that are commercially available in mobile applications (apps) stores and
      assess the involvement of eye care professionals in their development. MATERIALS
      AND METHODS: The Google play store and the Apple iTunes store were searched in
      July 2017 and updated in September 2017 for amblyopia games using the terms
      amblyopia, lazy eye, amblyopia therapy, lazy eye therapy, lazy eye exercises,
      amblyopia exercises, lazy eye games, and amblyopia games. General ophthalmology
      or optometry apps and apps in languages other than English were excluded.
      RESULTS: A total of 42 games were identified, 12 Android only (28%), 20 iOS only
      (48%), and 10 (24%) both Android and iOS. Most of the games were available under
      the medical category (60%). Most of the games were released in 2015. The price of
      the games ranged from $0.00 to $32.00 (USD). Nearly half of the games (45%) were
      to be played binocularly either using red-green goggles (38%) or a virtual
      reality set (7%). Only 7% of the games had explicitly documented the involvement
      of eye care professionals during game development. Only one game (app) was
      developed in collaboration with a research group and a children's hospital.
      CONCLUSIONS: This study identified that most of the currently available games do
      not have eye care professional input. An establishment of the quality assurance
      by a body of qualified eye care professionals could enhance the confidence of
      patients and clinicians using the game.

PMID- 29346039
TI  - Evaluation of a French Regional Telemedicine Network Dedicated to Neurological
      Emergencies: A 14-Year Study.
AB  - BACKGROUND: Equality in healthcare between urban and rural areas is problematic
      in France. Telemedicine networks are expected to improve equality in expertise
      assessment. We aimed to evaluate the use and impact of a regional rural French
      telemedicine network, dedicated to medical and surgical neurological emergencies,
      on interhospital patient transfers. METHODS: Eight community hospital emergency
      departments were remotely connected to the only university hospital in Franche
      Comte, France. We prospectively obtained data from all patients consecutively
      admitted to emergency care departments in the region and who received medical or
      neurosurgical expertise by telemedicine from January 2002 to December 2015. The
      reasons for requesting expertise, number of requested neurological opinions, and
      interhospital patient transfers were analyzed. Economic savings were determined
      by estimating the cost of avoided transfers. RESULTS: A total of 23,710 patients
      had telemedicine consultations in the region. The network was used by every
      community hospital (independently of the existence of local neurological teams).
      These consultations were overwhelmingly for cases of stroke (30%) and head or
      spinal injuries (36%). Cerebral tumors represented 9% of teleconsultations. In
      2015, 75% of patients admitted to the remote hospitals that did not have onsite
      neurological expertise nevertheless received neurovascular tele-expertise. The
      rate of thrombolyzed patients dramatically increased within 13 years regionally
      (9.9%) and 33.5% of thrombolyses were performed by telemedicine. The number of
      patients examined by telemedicine and admitted for head or spinal injuries also
      increased over the 13-year period (12% vs. 21%). Secondary interhospital
      transfers were halved for both pathologies. The estimated saving is ~?3.5
      million. CONCLUSION: Telemedicine networks facilitate acute-phase neurological
      assessment and prevent unnecessary secondary interhospital transfers.

PMID- 29346040
TI  - Bevacizumab Maintenance Versus No Maintenance During Chemotherapy-Free Intervals
      in Metastatic Colorectal Cancer: A Randomized Phase III Trial (PRODIGE 9).
AB  - Purpose Conflicting results are reported for maintenance treatment with
      bevacizumab during chemotherapy-free intervals (CFI) in metastatic colorectal
      cancer after induction chemotherapy. Patients and Methods In this open-label,
      phase III, randomized controlled trial, we compared the tumor control duration
      (TCD) observed with bevacizumab maintenance and with no treatment (observation)
      during CFI subsequent to induction chemotherapy with 12 cycles of fluorouracil,
      leucovorin, and irinotecan plus bevacizumab. After disease progression, the
      induction regimen was repeated for eight cycles, followed by a new CFI. Results
      From March 2010 to July 2013, 491 patients were randomly assigned. Disease
      progression or death occurred during induction chemotherapy in 85 patients (17%);
      261 patients (53%) had at least one reinduction, 107 (22%) had two reinductions,
      and 56 (11%) had three or more reinductions. The median TCD was 15 months in both
      groups; the median progression-free survival (PFS) from randomization was 9.2 and
      8.9 months in the maintenance group and observation groups, respectively. The TCD
      observed in both groups was higher compared with the TCD hypotheses of the trial.
      The median overall survival (OS) was 21.7 and 22.0 months in the maintenance and
      observation groups, respectively. In the per-protocol population, defined as
      patients with at least one reinduction after the first progression, the median
      duration of the first CFI was 4.3 months in both arms; the median TCD was 17.8
      and 23.3 months ( P = .339), the median PFS was 9.9 and 9.5 months, and the
      median OS was 27.6 and 28.5 months in the maintenance and observation groups,
      respectively. Multivariable analysis revealed that female gender, WHO performance
      status >= 2, and unresected primary tumors were associated with a shorter TCD.
      Conclusion Bevacizumab maintenance monotherapy did not improve TCD, CFI duration,
      PFS, or OS.

PMID- 29346041
TI  - Post-Treatment Mortality After Surgery and Stereotactic Body Radiotherapy for
      Early-Stage Non-Small-Cell Lung Cancer.
AB  - Purpose In early-stage non-small cell lung cancer (NSCLC), post-treatment
      mortality may influence the comparative effectiveness of surgery and stereotactic
      body radiotherapy (SBRT), with implications for shared decision making among high
      risk surgical candidates. We analyzed early mortality after these interventions
      using the National Cancer Database. Patients and Methods We abstracted patients
      with cT1-T2a, N0, M0 NSCLC diagnosed between 2004 and 2013 undergoing either
      surgery or SBRT. Thirty-day and 90-day post-treatment mortality rates were
      calculated and compared using Cox regression and propensity score-matched
      analyses. Results We identified 76,623 patients who underwent surgery (78%
      lobectomy, 20% sublobar resection, 2% pneumonectomy) and 8,216 patients who
      received SBRT. In the unmatched cohort, mortality rates were moderately increased
      with surgery versus SBRT (30 days, 2.07% v 0.73% [absolute difference (Delta),
      1.34%]; P < .001; 90 days, 3.59% v 2.93% [Delta, 0.66%]; P < .001). Among the
      27,200 propensity score-matched patients, these differences increased (30 days,
      2.41% v 0.79% [Delta, 1.62%]; P < .001; 90 days, 4.23% v 2.82% [Delta, 1.41%]; P
      < .001). Differences in mortality between surgery and SBRT increased with age,
      with interaction P < .001 at both 30 days and 90 days (71 to 75 years old: 30-day
      Delta, 1.87%; 90-day Delta, 2.02%; 76 to 80 years old: 30-day Delta, 2.80%; 90
      day Delta, 2.59%; > 80 years old: 30-day Delta, 3.03%; 90-day Delta, 3.67%; all P
      <= .001). Compared with SBRT, surgical mortality rates were higher with increased
      extent of resection (30-day and 90-day multivariate hazard ratio for mortality:
      sublobar resection, 2.85 and 1.37; lobectomy, 3.65 and 1.60; pneumonectomy, 14.5
      and 5.66; all P < 0.001). Conclusion Differences in 30- and 90-day post-treatment
      mortality between surgery and SBRT increased as a function of age, with the
      largest differences in favor of SBRT observed among patients older than 70 years.
      These representative mortality data may inform shared decision making among
      patients with early-stage NSCLC who are eligible for both interventions.

PMID- 29346042
TI  - Treatment of Malignant Pleural Mesothelioma: American Society of Clinical
      Oncology Clinical Practice Guideline.
AB  - Purpose To provide evidence-based recommendations to practicing physicians and
      others on the management of malignant pleural mesothelioma. Methods ASCO convened
      an Expert Panel of medical oncology, thoracic surgery, radiation oncology,
      pulmonary, pathology, imaging, and advocacy experts to conduct a literature
      search, which included systematic reviews, meta-analyses, randomized controlled
      trials, and prospective and retrospective comparative observational studies
      published from 1990 through 2017. Outcomes of interest included survival, disease
      free or recurrence-free survival, and quality of life. Expert Panel members used
      available evidence and informal consensus to develop evidence-based guideline
      recommendations. Results The literature search identified 222 relevant studies to
      inform the evidence base for this guideline. Recommendations Evidence-based
      recommendations were developed for diagnosis, staging, chemotherapy, surgical
      cytoreduction, radiation therapy, and multimodality therapy in patients with
      malignant pleural mesothelioma. Additional information is available at
      www.asco.org/thoracic-cancer-guidelines and www.asco.org/guidelineswiki .

PMID- 29346043
TI  - Analysis of Margin Classification Systems for Assessing the Risk of Local
      Recurrence After Soft Tissue Sarcoma Resection.
AB  - Purpose To compare the ability of margin classification systems to determine
      local recurrence (LR) risk after soft tissue sarcoma (STS) resection. Methods Two
      thousand two hundred seventeen patients with nonmetastatic extremity and truncal
      STS treated with surgical resection and multidisciplinary consideration of
      perioperative radiotherapy were retrospectively reviewed. Margins were coded by
      residual tumor (R) classification (in which microscopic tumor at inked margin
      defines R1), the R+1mm classification (in which microscopic tumor within 1 mm of
      ink defines R1), and the Toronto Margin Context Classification (TMCC; in which
      positive margins are separated into planned close but positive at critical
      structures, positive after whoops re-excision, and inadvertent positive margins).
      Multivariate competing risk regression models were created. Results By R
      classification, LR rates at 10-year follow-up were 8%, 21%, and 44% in R0, R1,
      and R2, respectively. R+1mm classification resulted in increased R1 margins (726
      v 278, P < .001), but led to decreased LR for R1 margins without changing R0 LR;
      for R0, the 10-year LR rate was 8% (range, 7% to 10%); for R1, the 10-year LR
      rate was 12% (10% to 15%) . The TMCC also showed various LR rates among its tiers
      ( P < .001). LR rates for positive margins on critical structures were not
      different from R0 at 10 years (11% v 8%, P = .18), whereas inadvertent positive
      margins had high LR (5-year, 28% [95% CI, 19% to 37%]; 10-year, 35% [95% CI, 25%
      to 46%]; P < .001). Conclusion The R classification identified three distinct
      risk levels for LR in STS. An R+1mm classification reduced LR differences between
      R1 and R0, suggesting that a negative but < 1-mm margin may be adequate with
      multidisciplinary treatment. The TMCC provides additional stratification of
      positive margins that may aid in surgical planning and patient education.

PMID- 29346045
TI  - In This Issue * February 1, 2018.

PMID- 29346044
TI  - Clinical features, treatment, and outcomes of cutaneous and oral squamous cell
      carcinoma in avian species.
AB  - OBJECTIVE To determine the clinical features, treatment, and outcomes of
      treatment for oral and cutaneous squamous cell carcinoma (SCC) in avian species.
      DESIGN Retrospective case series with nested cohort study. ANIMALS 87 client
      owned birds of various species with histologically confirmed SCC of the skin or
      oral cavity. PROCEDURES Clinicians entered case information through an online
      survey tool. Data were collected regarding patient signalment, concurrent
      conditions, treatments, adverse effects, and clinical outcomes. Relationships
      were examined between complete excision and partial or complete response.
      Survival analysis was performed to compare outcomes among groupings of
      therapeutic approaches. RESULTS Only 7 of 64 (11%) birds for which full outcome
      data were available had complete remission of SCC; 53 (83%) had progressive
      disease, were euthanized, or died of the disease. The unadjusted OR for partial
      or complete response following complete tumor excision (vs other treatment
      approaches) was 6.9 (95% confidence interval [CI], 1.8 to 25.8). Risk of death
      was 62% lower (hazard ratio, 0.38; 95% CI, 0.19 to 0.77) for birds that underwent
      complete excision versus conservative treatment. Median survival time from
      initial evaluation for birds receiving complete excision was 628 days (95% CI,
      210 to 1,008 days), compared with 171 days (95% CI, 89 to 286 days) for birds
      receiving monitoring with or without conservative treatment. Birds receiving any
      other additional treatment had a median survival time of 357 days (95% CI, 143 to
      562 days). CONCLUSIONS AND CLINICAL RELEVANCE For birds with SCC, complete
      excision was the only treatment approach significantly associated with complete
      or partial response and increased survival time.

PMID- 29346046
TI  - Ultrasonographic characteristics of the reproductive tract and serum progesterone
      and estradiol concentrations in captive female red wolves (Canis rufus) with and
      without reproductive tract disease.
AB  - OBJECTIVE To describe ultrasonographic characteristics of the reproductive tract
      and serum progesterone and estradiol concentrations in captive female red wolves
      (Canis rufus) with and without reproductive tract disease. DESIGN Prospective
      study. ANIMALS 13 adult female red wolves. PROCEDURES Wolves with varying parity
      and history of contraceptive treatment were anesthetized to facilitate
      ultrasonographic examination and measurement of the reproductive tract and blood
      collection for determination of serum progesterone and estradiol concentrations
      in December 2011 and June 2012. Additionally, during the December evaluation,
      fine-needle aspirate samples of the uterus were obtained for cytologic
      evaluation. Measurements were compared between wolves with and without
      reproductive tract disease and between wolves that had and had not received a
      contraceptive. RESULTS 7 of 13 wolves had or developed reproductive tract disease
      during the study. Ranges for measurements of reproductive tract structures
      overlapped between ultrasonographically normal and abnormal tracts, but
      measurements for abnormal tracts were generally greater than those for normal
      tracts. The ultrasonographic diagnosis was consistent with the histologic
      diagnosis for reproductive tracts obtained from wolves that were sterilized, were
      euthanized, or died during the study. Cytologic results for fine-needle aspirate
      samples of the uterus and serum progesterone and estradiol concentrations were
      unable to distinguish wolves with and without reproductive tract disease.
      Reproductive tract disease was not associated with parity or contraceptive
      administration. CONCLUSIONS AND CLINICAL RELEVANCE The ultrasonographic images,
      reproductive tract measurements, and descriptions of reproductive tract lesions
      provided in this study can be used as diagnostic guidelines for the treatment and
      management of red wolves with reproductive tract disease.

PMID- 29346047
TI  - Cultivating our next generation of leaders.

PMID- 29346048
TI  - Risk factors and prognostic indicators for surgical outcome of dogs with
      esophageal foreign body obstructions.
AB  - OBJECTIVE To determine risk factors for surgical intervention, complications, and
      outcome in dogs with an esophageal foreign body (EFB). DESIGN Retrospective
      observational study. ANIMALS 224 incidents of EFB in 223 dogs evaluated at a
      veterinary teaching hospital from 1995 through 2014. PROCEDURES Hospital records
      were reviewed to collect data regarding signalment, history, clinical signs, EFB
      type and location, procedures, complications, and outcomes. Breed distributions
      were compared between dogs with EFB and the entire canine patient population
      during the study period. Variables were tested for associations with each other
      and with outcomes. RESULTS Terrier breeds were most common (71/233 [30.5%]).
      Duration of EFB entrapment, body weight, anorexia, lethargy, rectal temperature,
      and esophageal perforation were associated with the need for surgical
      intervention. Older age, longer duration of EFB entrapment, and perforation were
      associated with a poorer prognosis. Endoscopic retrieval or advancement into the
      stomach was successful for 183 of 219 (83.6%) EFBs, and 16 of 143 (11.2%)
      entrapments resulted in postprocedural esophageal stricture. Overall median
      duration of hospitalization was brief (1 day), and the need for surgical
      intervention was associated with a longer duration. Overall mortality rate was
      5.4% (12/223); 90 of 102 (88.2%) dogs with a median follow-up period of 27 months
      after EFB treatment had an excellent outcome. CONCLUSIONS AND CLINICAL RELEVANCE
      Study findings suggested that endoscopic EFB retrieval remains the initial
      treatment option of choice for affected dogs, provided that esophageal
      perforation does not necessitate surgical intervention. Although esophageal
      stricture formation was the most common complication, the overall rate of this
      outcome was low.

PMID- 29346049
TI  - Microphthalmia, corneal dermoids, and congenital anomalies resembling Goldenhar
      syndrome in a cat.
AB  - CASE DESCRIPTION An 18-month-old spayed female domestic shorthair cat was
      evaluated because of conjunctivitis and skin-fold dermatitis secondary to
      bilateral microphthalmia, corneal dermoids, and ankyloblepharon. CLINICAL
      FINDINGS Physical examination revealed bilateral microphthalmia, bilaterally
      symmetrical corneal dermoids, ankyloblepharon, superior and inferior entropion,
      prognathism, and facial asymmetry with deviation of the nasal septum. Computed
      tomography revealed malformed, thickened bony orbits with mineralization of the
      orbital ligament bilaterally. Moderate rightward deviation of the nasal septum
      and ventral nasal meatus was also evident, with no identifiable maxillary
      sinuses. Results of MRI of the brain were unremarkable. Abdominal ultrasonography
      showed an irregularly marginated left kidney and a right kidney defect suggestive
      of chronic renal infarction. An abnormal, well-demarcated, focally thickened
      region of the muscularis externa of the jejunum was also evident. TREATMENT AND
      OUTCOME Transpalpebral enucleation was performed bilaterally. Histologic
      examination of ocular tissues confirmed the corneal dermoids and microphthalmia
      with anterior and posterior segment dysgenesis and cataracts in both eyes. Ocular
      discomfort resolved after postoperative recovery, and follow-up revealed that the
      patient's activity level and quality of life were excellent. No clinical signs of
      upper respiratory, urinary, or gastrointestinal tract disease were observed
      during the approximately 3.5-year follow-up period. CLINICAL RELEVANCE The
      congenital abnormalities observed resembled those described for human patients
      with Goldenhar syndrome, and the outcome of treatment was favorable. This report
      may prompt clinicians to consider this diagnosis when evaluating young cats with
      similar clinical signs.

PMID- 29346050
TI  - Diagnosis and management of inflammatory bowel disease in a harpy eagle (Harpia
      harpyja) with suspected fenbendazole toxicosis.
AB  - CASE DESCRIPTION A 14-year-old 4.1-kg (9.02-lb) male harpy eagle (Harpia harpyja)
      was evaluated because of vomiting, anorexia, lethargy, and weight loss (decrease
      of 0.35 kg [0.77 lb]) of 4 weeks' duration. The bird had previously been treated
      orally with fenbendazole after the initial onset of clinical signs. CLINICAL
      FINDINGS An initial CBC revealed marked heteropenia and anemia, but whole-body
      contrast-enhanced CT images and other diagnostic test findings were unremarkable.
      Clinical signs persisted, and additional diagnostic testing failed to reveal the
      cause. During celiotomy, a biopsy specimen of the duodenum was obtained for
      histologic examination, which revealed lymphoplasmacytic inflammation, consistent
      with inflammatory bowel disease (IBD). TREATMENT AND OUTCOME Prior to
      histopathologic diagnosis of IBD, barium sulfate administered via gavage resulted
      in a temporary improvement of clinical signs. Following diagnosis of IBD,
      corticosteroid administration was initiated in conjunction with antifungal
      prophylaxis. Cessation of vomiting and a return to normal appetite occurred
      within 3 days. Fifteen months after cessation of corticosteroid treatment, the
      eagle continued to do well. CLINICAL RELEVANCE To our knowledge, this was the
      first report of diagnosis and management of IBD in an avian species. For the
      eagle of the present report, results of several diagnostic tests increased
      clinical suspicion of IBD, but histologic examination of an intestinal biopsy
      specimen was required for definitive diagnosis. Although successful in this case,
      steroid administration in avian species must be carefully considered. Conclusive
      evidence of fenbendazole toxicosis was not obtained, although it was highly
      suspected in this bird.

PMID- 29346051
TI  - Diagnosis, treatment, and outcome of and risk factors for ophthalmic disease in
      leopard geckos (Eublepharis macularius) at a veterinary teaching hospital: 52
      cases (1985-2013).
AB  - OBJECTIVE To describe diagnosis, treatment, and outcome of and risk factors for
      ophthalmic disease in leopard geckos (Eublepharis macularius) evaluated at a
      veterinary teaching hospital. DESIGN Retrospective case series. ANIMALS 112 of
      144 (78%) leopard geckos that were evaluated at a veterinary teaching hospital in
      January 1985 through October 2013 and for which sufficient medical record
      information was available. PROCEDURES Information from medical records was used
      to identify leopard geckos with ophthalmic disease, characterize cases, and
      determine risk factors for the presence of ophthalmic disease. RESULTS Of the 112
      leopard geckos, 52 (46%) had ophthalmic disease (mainly corneal or conjunctival
      disease). Female geckos were less likely to have ophthalmic disease, and there
      was a positive association between increasing age and ophthalmic disease. Use of
      a paper towel substrate, absence of any heat source, and lack of vitamin A
      supplementation were positively associated with a diagnosis of ophthalmic
      disease. Head dysecdysis was the only concurrent disorder significantly
      associated with ophthalmic disease. At necropsy, 5 affected leopard geckos had
      squamous metaplasia of the conjunctivae. CONCLUSIONS AND CLINICAL RELEVANCE
      Results indicated that ophthalmic disease is a common finding in leopard geckos.
      The cause of ocular surface disease in leopard geckos may be multifactorial, and
      hypovitaminosis A may be an important risk factor. Although animals receiving
      supplemental vitamin A were less likely to have ophthalmic disease, further
      understanding is required regarding the metabolism of and nutritional
      requirements for vitamin A in leopard geckos.

PMID- 29346052
TI  - Pathology in Practice.

PMID- 29346053
TI  - What Is Your Diagnosis?

PMID- 29346055
TI  - Pathology in Practice.

PMID- 29346056
TI  - Esophageal leiomyoma in a dog causing esophageal distension and treated by
      transcardial placement of a self-expanding, covered, nitinol esophageal stent.
AB  - CASE DESCRIPTION A 10-year-old spayed female Rottweiler was referred for
      evaluation because of a 2-month history of regurgitation and weight loss, despite
      no apparent change in appetite. The dog had received antiemetic and antacid
      treatment, without improvement. CLINICAL FINDINGS Physical examination revealed a
      low body condition score (2/5), but other findings were unremarkable. Diffuse,
      global esophageal dilatation was noted on plain thoracic radiographs, and normal
      motility was confirmed through videofluoroscopic evaluation of swallowing.
      Transhepatic ultrasonographic and CT examination revealed a circumferential,
      intraparietal lesion in the distal portion of the esophagus causing distal
      esophageal or cardial subobstruction and no metastases. Incisional biopsy of the
      lesion was performed, and findings of histologic examination supported a
      diagnosis of esophageal leiomyoma. TREATMENT AND OUTCOME In view of numerous
      possible complications associated with esophageal surgery, the decision was made
      to palliatively treat the dog by transcardial placement of a self-expanding,
      covered, nitinol esophageal stent under endoscopic guidance. Two weeks after
      stent placement, radiography revealed complete migration of the stent into the
      gastric lumen. Gastrotomy was performed, and the stent was replaced and fixed in
      place. Twenty-four months after initial stent placement, the dog had a healthy
      body condition and remained free of previous clinical signs. CLINICAL RELEVANCE
      Diffuse benign muscular neoplasia should be considered as a differential
      diagnosis for acquired esophageal dilatation in adult and elderly dogs. In the
      dog of this report, transcardial stent placement resulted in resolution of the
      clinical signs, with no apparent adverse effect on digestive function. The
      described procedure could be beneficial for nonsurgical treatment of benign
      esophageal tumors in dogs.

PMID- 29346057
TI  - Anesthesia Case of the Month.

PMID- 29346058
TI  - How Much Do We Spend? Creating Historical Estimates of Public Health Expenditures
      in the United States at the Federal, State, and Local Levels.
AB  - The United States has a complex governmental public health system. Agencies at
      the federal, state, and local levels all contribute to the protection and
      promotion of the population's health. Whether the modern public health system is
      well situated to deliver essential public health services, however, is an open
      question. In some part, its readiness relates to how agencies are funded and to
      what ends. A mix of Federalism, home rule, and happenstance has contributed to a
      siloed funding system in the United States, whereby health agencies are given
      particular dollars for particular tasks. Little discretionary funding remains.
      Furthermore, tracking how much is spent, by whom, and on what is notoriously
      challenging. This review both outlines the challenges associated with estimating
      public health spending and explains the known sources of funding that are used to
      estimate and demonstrate the value of public health spending.

PMID- 29346059
TI  - Fermented Extraction of Citrus unshiu Peel Inhibits Viability and Migration of
      Human Pancreatic Cancers.
AB  - Pancreatic cancer is one of the most dangerous cancers with high mortality rates.
      Despite continuous efforts, there has been limited improvement in its prognosis.
      In this study, we prepared fermented extract of Citrus unshiu peel (fCUP) from
      the by-product after juice processing and then examined the anticancer effects of
      fCUP on human pancreatic cancer cells. Treatment with fCUP inhibited the growth
      of human pancreatic cancer cells through induction of caspase-3 cleavage both in
      vitro and in vivo. Treatment with fCUP also blocked the migration of human
      pancreatic cancer cells through activation of intracellular signaling pathways
      such as MKK3/6 and P38. In contrast, treatment with fCUP did not inhibit growth
      and migration of human umbilical vein endothelial cells. In addition, we found
      that fCUP mainly consisted of aboriginal compounds, narirutin and hesperidin, as
      well as newly generated compounds, naringenin and hesperetin. In silico analysis
      showed that naringenin and hesperetin were the unique modules related to
      anticancer effect. Furthermore, fCUP exhibited the anticancer effects in in vivo
      xenograft models. Collectively, these results suggest that fCUP might have the
      potential to be developed into an effective anticancer drug for pancreatic
      cancers without causing adverse side-effects.

PMID- 29346060
TI  - A Combination with Probiotic Complex, Zinc, and Coenzyme Q10 Attenuates
      Autoimmune Arthritis by Regulation of Th17/Treg Balance.
AB  - Probiotic complex, zinc, and coenzyme Q10 (CoQ10) are recognized dietary
      supplements with an anti-inflammatory role. Although these supplementations are
      individually known to benefit rheumatoid arthritis (RA), there is no evidence
      suggesting any synergic effect. The primary goal of this study is to determine
      whether probiotic complex, zinc, and CoQ10 attenuate the development of collagen
      induced arthritis (CIA). The combination of probiotic complex, zinc, and CoQ10
      reduced CIA severity by downregulating the levels of IgG, IgG1, and IgG2a in
      serum. Joint inflammation, bone destruction, and cartilage damage were also
      improved by the complex. There was a decrease in the expression of tumor necrosis
      factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, IL-17, and vascular endothelial
      growth factor (VEGF) in the joint synovium. The balance between helper T 17
      (Th17) cells and regulatory T (Treg) cells was shown to be controlled
      reciprocally by the complex. These findings suggest that the combination of
      probiotic complex, zinc, and CoQ10 can ameliorate the development of CIA by
      inhibiting the expression of proinflammatory cytokines, and is thus an important
      therapeutic candidate for RA treatment.

PMID- 29346061
TI  - Two Cases of Dengue Fever Imported from Egypt to Russia, 2017.
AB  - In 2017, two cases of dengue fever were imported from Hurghada, Egypt, where
      dengue fever was not considered endemic, to Moscow. These cases show how
      emergence of dengue fever in popular resort regions on the coast of the Red Sea
      can spread infection to countries where it is not endemic.

PMID- 29346062
TI  - Television Viewing Time, Physical Activity, and Mortality Among African
      Americans.
AB  - BACKGROUND: Prolonged television viewing time, a marker of sedentary activity, is
      independently associated with increased all-cause mortality; however, this
      association has rarely been studied in African Americans. The objective of our
      study was to examine the association between television viewing time and
      mortality among African Americans by using data from the Jackson Heart Study
      (JHS). METHODS: We studied 5,289 participants from the JHS study who reported
      television viewing time (h/day) in the JHS baseline questionnaire from 2000
      through 2004. Using multivariable Cox regression models adjusted for age, sex,
      smoking, alcohol use, physical activity, nutrition, prevalent coronary heart
      disease, chronic kidney disease, diabetes, and hypertension, we computed hazard
      ratios to examine the association between television viewing time (<=2 h/day, 2-4
      h/day, and >=4 h/day) and mortality. RESULTS: Participants had a mean age of 55
      years, and 64% were women. After a median follow-up of 9.9 years (interquartile
      range, 9.0-10.7), 615 deaths occurred (data analysis conducted in 2017). Hazard
      ratios for mortality were 1.08 (0.86-1.37) for television time of 2 to 4 hours
      per day and 1.48 (95% CI: 1.19-1.83) for television time of greater than or equal
      to 4 hours per day when compared with those who watched television less than 2
      hours per day (P trend = .002). When we restricted analyses to those who
      performed leisure-time activities, the hazard ratios for mortality were 1.10 (95%
      CI, 0.84-1.45) for television viewing of 2 to 4 hours per day and 1.45 (95% CI,
      1.13-1.86) for more than 4 hours per day compared with the less than 2 hours per
      day. CONCLUSION: Our findings suggest that greater television viewing time, even
      among those who perform leisure-time physical activities, is associated with
      increased all-cause mortality among African Americans. Thus, it may serve as an
      indicator of a sedentary lifestyle with potential for intervention.

PMID- 29346063
TI  - Linking Data From Health Surveys and Electronic Health Records: A Demonstration
      Project in Two Chicago Health Center Clinics.
AB  - INTRODUCTION: Monitoring and understanding population health requires conducting
      health-related surveys and surveillance. The objective of our study was to assess
      whether data from self-administered surveys could be collected electronically
      from patients in urban, primary-care, safety-net clinics and subsequently linked
      and compared with the same patients' electronic health records (EHRs). METHODS:
      Data from self-administered surveys were collected electronically from a
      convenience sample of 527 patients at 2 Chicago health centers from September
      through November, 2014. Survey data were linked to EHRs. RESULTS: A total of 251
      (47.6%) patients who completed the survey consented to having their responses
      linked to their EHRs. Consenting participants were older, more likely to report
      fair or poor health, and took longer to complete the survey than those who did
      not consent. For 8 of 18 categorical variables, overall percentage of agreement
      between survey data and EHR data exceeded 80% (sex, race/ethnicity, pneumococcal
      vaccination, self-reported body mass index [BMI], diabetes, high blood pressure,
      medication for high blood pressure, and hyperlipidemia), and of these, the level
      of agreement was good or excellent (kappa >=0.64) except for pneumococcal
      vaccination (kappa = 0.40) and hyperlipidemia (kappa = 0.47). Of 7 continuous
      variables, agreement was substantial for age and weight (concordance coefficients
      >=0.95); however, with the exception of calculated survey BMI and EHR-BMI
      (concordance coefficient = 0.88), all other continuous variables had poor
      agreement. CONCLUSIONS: Self-administered and web-based surveys can be completed
      in urban, primary-care, safety-net clinics and linked to EHRs. Linking survey and
      EHR data can enhance public health surveillance by validating self-reported data,
      completing gaps in patient data, and extending sample sizes obtained through
      current methods. This approach will require promoting and sustaining patient
      involvement.

PMID- 29346064
TI  - Using Two Disability Measures to Compare Physical Inactivity Among US Adults With
      Disabilities.
AB  - Prevalence of health behaviors among adults with disabilities may vary by
      disability measure. We used data from the 2011-2015 National Health Interview
      Survey to estimate prevalence of physical inactivity by disability status using 2
      measures of disability: Basic Actions Difficulty questions (BADQ) and a standard
      6-question measure (6Q). Disability prevalence (BADQ, 31.1%; 6Q, 17.5%) and
      inactivity prevalence among adults with disability (BADQ, 42.9%; 6Q, 52.5%) and
      without disability (BADQ, 24.3%; 6Q, 26.2%) varied by measure; however, both
      measures highlight inactivity disparities for adults with disability. Disability
      measures influence physical inactivity estimates and are important for guiding
      surveillance and health promotion activities for adults with disabilities.

PMID- 29346065
TI  - Accuracy of Principal and Teacher Knowledge of School District Policies on Sun
      Protection in California Elementary Schools.
AB  - INTRODUCTION: Policy is a key aspect of school-based efforts to prevent skin
      cancer. We explored the extent and accuracy of knowledge among principals and
      teachers in California public school districts about the elements specified in
      their district's written sun safety policy. METHODS: The sample consisted of
      California public school districts that subscribed to the California School
      Boards Association, had an elementary school, adopted Board Policy 5141.7 for sun
      safety, and posted it online. The content of each policy was coded. Principals (n
      = 118) and teachers (n = 113) in elementary schools were recruited from September
      2013 through December 2015 and completed a survey on sun protection policies and
      practices from January 2014 through April 2016. RESULTS: Only 38 of 117
      principals (32.5%) were aware that their school district had a sun protection
      policy. A smaller percentage of teachers (13 of 109; 11.9%) than principals were
      aware of the policy (F108 = 12.76, P < .001). We found greater awareness of the
      policy among principals and teachers who had more years of experience working in
      public education (odds ratio [OR] = 1.05, F106 = 4.71, P = .03) and worked in
      schools with more non-Hispanic white students (OR = 7.65, F109 = 8.61, P = .004)
      and fewer Hispanic students (OR = 0.28, F109 = 4.27, P = .04). CONCLUSION: Policy
      adoption is an important step in implementing sun safety practices in schools,
      but districts may need more effective means of informing school principals and
      teachers of sun safety policies. Implementation will lag without clear
      understanding of the policy's content by school personnel.

PMID- 29346066
TI  - Expression of autophagy related genes in chronic lymphocytic leukemia is
      associated with disease course.
AB  - Autophagy leads cells to different fates in various cell types and under diverse
      contexts. Chronic lymphocytic leukemia (CLL), an incurable hematologic neoplasm,
      has highly variable course and its heterogeneity prompts interest in exploring
      autophagic trajectories in CLL. We detected the mRNA levels of two autophagy
      related genes, BECN1 and ATG5, assessed the association between expression levels
      and clinical characteristics, and did survival analysis. One hundred and six
      patients with CLL and fifty healthy controls were enrolled in the present study.
      CLL samples were found higher expression levels of BECN1 and ATG5 mRNA compared
      with healthy controls. Further confirmation at the protein level performed in a
      small cohort of patients, which included Beclin1, ATG5 and LC3-II showed the same
      trend. What's more, high expression at the mRNA level correlated with early Binet
      stage, isolated 13q deletion and negative CD38, which were associated with favor
      prognosis, suggesting that autophagy differs in CLL due to the presence of
      heterogeneity and high levels of these two genes may reflect better outcomes.
      Survival analysis did show patients with high expression of ATG5 mRNA had longer
      treatment free survival from the date of sampling.

PMID- 29346067
TI  - The association between child maltreatment and adult poverty - A systematic
      review of longitudinal research.
AB  - Child maltreatment is a global problem affecting millions of children and is
      associated with an array of cumulative negative outcomes later in life, including
      unemployment and financial difficulties. Although establishing child maltreatment
      as a causal mechanism for adult economic outcomes is fraught with difficulty,
      understanding the relationship between the two is essential to reducing such
      inequality. This paper presents findings from a systematic review of longitudinal
      research examining experiences of child maltreatment and economic outcomes in
      adulthood. A systematic search of seven databases found twelve eligible
      retrospective and prospective cohort studies. From the available evidence, there
      was a relatively clear relationship between 'child maltreatment' and poorer
      economic outcomes such as reduced income, unemployment, lower level of job skill
      and fewer assets, over and above the influence of family of origin socio-economic
      status. Despite an extremely limited evidence base, neglect had a consistent
      relationship with a number of long-term economic outcomes, while physical abuse
      has a more consistent relationship with income and employment. Studies examining
      sexual abuse found less of an association with income and employment, although
      they did find a relationship other outcomes such as sickness absence, assets,
      welfare receipt and financial insecurity. Nonetheless, all twelve studies showed
      some association between at least one maltreatment type and at least one economic
      measure. The task for future research is to clarify the relationship between
      specific maltreatment types and specific economic outcomes, taking account of how
      this may be influenced by gender and life course stage.

PMID- 29346068
TI  - Prevalence of hypertension and prehypertension among a coastal population in
      south India: baseline findings from a population-based health registry project in
      Kerala.

PMID- 29346069
TI  - The prevalence and influencing factors for child neglect in a rural area of Anhui
      province: a 2-year follow-up study.
AB  - OBJECTIVES: The purpose of the current study was to identify the change of
      prevalence and influencing factors for child neglect in a rural area of Anhui
      province through the 2-year follow-up study. STUDY DESIGN: Longitudinal study
      with 2-year follow-up. METHODS: Analyses were based on data from a longitudinal
      study, performed in five elementary schools and three secondary schools in
      Changfeng County. A total of 816 children aged between 7 and 16 years completed
      the three assessments during the period of 2009-2011. Generalized estimating
      equations (GEEs) were applied to identify the influencing factors of child
      neglect. RESULTS: The prevalence of child neglect was 67.8%, 56.6%, and 57.7% at
      the three assessments, respectively. There were 272 children (33.3%) having
      consistently experiencing neglect during three assessments and 106 (13.0%)
      children had not suffered from neglect during three assessments. Among 553
      participants who experienced neglect at the first assessment, 105 (19.0%)
      children no longer met the diagnosis at the next two assessments. Fifty-two
      children who did not suffer from neglect at the first assessment experienced
      neglect at the final assessment. The results of GEEs showed that child neglect
      was clearly associated with age (odds ratio [OR] = 0.95, 95% confidence interval
      [CI] = 0.92-0.99, P = 0.016), male gender (OR = 1.20, 95% CI = 1.00-1.43, P =
      0.047), siblings (OR = 1.26, 95% CI = 1.03-1.55, P = 0.028), parental marital
      disruption (OR = 2.02, 95% CI = 1.09-3.78, P = 0.027), left-behind status (OR =
      1.26, 95% CI = 1.06-1.49, P = 0.008), severe family dysfunction (OR = 1.46, 95%
      CI = 1.03-2.07, P = 0.035), quality of life (OR = 0.98, 95% CI = 0.98-0.99, P <
      0.001), positive coping styles (OR = 0.97, 95% CI = 0.94-0.99, P = 0.001), and
      negative coping styles (OR = 1.03, 95% CI = 1.02-1.05, P < 0.001). CONCLUSION:
      Our studies detected the decreased prevalence of child neglect across the three
      assessments. Additionally, some sociodemographic, psychosocial and family risk
      factors of child neglect were identified, which will be helpful for child neglect
      prevention strategies development and implementation in China.

PMID- 29346070
TI  - Key pharmacovigilance stakeholders' experiences of direct patient reporting of
      adverse drug reactions and their prospects of future development in the European
      Union.
AB  - OBJECTIVES: In the European Union (EU), legislation allows patients to directly
      report adverse drug reactions (ADRs) to competent authorities. Five years after
      its implementation, patient reporting is not equal in all countries. This study
      aimed to explore key stakeholders' perceptions of patient reporting in four EU
      countries. STUDY DESIGN: Qualitative study design. METHODS: Twelve
      representatives from national pharmacovigilance centres and/or authorities as
      well as national pharmaceutical industry bodies in four EU countries participated
      in the study. Supranational organizations were also included. Data collection was
      via face-semi-structured interviews. Inductive content analysis was performed
      thereafter, applying principles of risk management as a theoretical framework.
      RESULTS: Four themes (attitudes and beliefs, system maturation factors,
      regulatory improvements, and cultural shifts) emerged, conceptually
      interconnected. Participants from countries introducing patient reporting
      recently expressed a negative attitude. Participants highlighted the need for
      additional resources, both human and financial, to address patient reporting and
      associated advantages. CONCLUSIONS: The findings identified perceived barriers
      and facilitators of patient reporting. The involvement of patients, use of
      information, and dissemination of patient reporting are far from optimal. A
      better integration of the work by EU regulatory authorities is recommended.

PMID- 29346071
TI  - Identification of potential inhibitors against nuclear Dam1 complex subunit Ask1
      of Candida albicans using virtual screening and MD simulations.
AB  - Identification of hit compounds against specific target form the starting point
      for a drug discovery program. A consistent decline of new chemical entities
      (NCEs) in recent years prompted a challenge to explore newer approaches to
      discover potential hit compounds that in turn can be converted into leads, and
      ultimately drug with desired therapeutic efficacy. The vast amount of omics and
      activity data available in public databases offers an opportunity to identify
      novel targets and their potential inhibitors. State of the art in silico methods
      viz., clustering of compounds, virtual screening, molecular docking, MD
      simulations and MMPBSA calculations were employed in a pipeline to identify
      potential 'hits' against those targets as well whose structures, as of now, could
      only predict through threading approaches. In the present work, we have started
      from scratch, amino acid sequence of target and compounds retrieved from PubChem
      compound database, modeled it in such a way that led to the identification of
      possible inhibitors of Dam1 complex subunit Ask1 of Candida albicans. We also
      propose a ligand based binding site determination approach. We have identified
      potential inhibitors of Ask1 subunit of a Dam1 complex of C. albicans, which is
      required to prevent precocious spindle elongation in pre-mitotic phases. The
      proposed scheme may aid to find virtually potential inhibitors of other unique
      targets against candida.

PMID- 29346072
TI  - Synthesis, biological evaluation and molecular docking studies of novel
      benzimidazole derivatives.
AB  - A novel series of N-substituted-benzimidazolyl linked para substituted
      benzylidene based molecules containing three pharmacologically potent hydrogen
      bonding parts namely; 2,4-thiazolidinedione (TZD: a 2,4-dicarbonyl), diethyl
      malonate (DEM: a 1,3-diester and an isooxazolidinedione analog) and methyl
      acetoacetate (MAA: a beta-ketoester) (6a-11b) were synthesized and evaluated for
      in vitro alpha-glucosidase inhibition. The structure of the novel synthesized
      compounds was confirmed through the spectral studies (LC-MS, 1H NMR, 13C NMR, FT
      IR). Comparative evaluation of these compounds revealed that the compound 9b
      showed maximum inhibitory potential against alpha-amylase and alpha-glucosidase
      giving an IC50 value of 0.54 +/- 0.01 MUM. Furthermore, binding affinities in
      terms of G score values and hydrogen bond interactions between all the
      synthesized compounds and the AA residues in the active site of the protein (PDB
      code: 3TOP) to that of Acarbose (standard drug) were explored with the help of
      molecular docking studies. Compound 9b was considered as promising candidate of
      this series.

PMID- 29346073
TI  - Extensive conservation of prokaryotic ribosomal binding sites in known and novel
      picobirnaviruses.
AB  - Currently, the Leviviridae and Cystoviridae are the only two recognized families
      of prokaryotic RNA viruses. Picobirnaviruses, which are bisegmented double
      stranded RNA viruses commonly found in animal stool samples, are currently
      thought to be animal viruses, but have not been propagated in cell culture or in
      an animal model. We hypothesize that picobirnaviruses are prokaryotic RNA
      viruses. We identified and analyzed the genomes of 38 novel picobirnaviruses and
      determined that a classical bacterial sequence motif, the ribosomal binding site
      (RBS), is present in the 5' untranslated regions (5' UTRs) of all of the novel as
      well as all previously published picobirnavirus sequences. Among all viruses,
      enrichment of the RBS motif is only observed in viral families that infect
      prokaryotes and not in eukaryotic infecting viral families. These results will
      enable future studies to more accurately understand the biology of
      picobirnaviruses.

PMID- 29346074
TI  - A partial deletion within foot-and-mouth disease virus non-structural protein 3A
      causes clinical attenuation in cattle but does not prevent subclinical infection.
AB  - Deletions within the 3A coding region of foot-and-mouth disease virus (FMDV) are
      associated with decreased virulence in cattle; however, the mechanisms are
      unknown. We compared experimental infection of cattle with virulent FMDV O1Campos
      (O1Ca) and a mutant derivative (O1Ca?3A) lacking residues 87-106 of 3A.
      Unexpectedly, primary infection of the nasopharyngeal mucosa was similar for both
      viruses. However, while O1Ca caused viremia and fulminant clinical disease,
      O1Ca?3A infection was subclinical and aviremic. There were no differences in
      expression of anti-viral cytokines in nasopharyngeal tissues between the groups,
      suggesting attenuation by O1Ca?3A was a consequence of reduced replication
      efficiency in bovine cells, rather than a difference in the host response. These
      results demonstrated that although deletion in 3A of FMDV confers a clinically
      attenuated phenotype in cattle, the deletion does not prevent subclinical
      infection. These findings have implications for field scenarios involving
      outbreaks with apparently host-limited strains of FMDV.

PMID- 29346076
TI  - Ultrasensitive electrochemical immuno-sensing platform based on gold
      nanoparticles triggering chlorpyrifos detection in fruits and vegetables.
AB  - Chlorpyrifos (chl) is an organophosphate pesticide extensively used in
      agriculture and highly toxic for human health. Fluorine doped tin-oxide (FTO)
      based electrochemical nanosensor was developed for chlorpyrifos detection with
      gold nanoparticles (AuNPs) and anti-chlorpyrifos antibodies (chl-Ab). AuNPs
      provides high electrical conductivity and specific resistivity, thus increases
      the sensitivity of immunoassay. High electrical conductivity of AuNPs reveals
      that it promotes the redox reaction for better cyclic voltammetry. Based on the
      intrinsic conductive properties of FTO-AuNPs complex, chl-Ab was immobilized onto
      AuNPs surface. Under optimized conditions, the proposed FTO based nanosensor
      exhibited high sensitivity and stable response for the detection of chlorpyrifos,
      ranging from 1fM to 1uM with limit of detection (LOD) up to 10fM. The FTO-AuNPs
      sensor was successfully employed for the detection of chlorpyrifos in standard as
      well in real samples up to 10nM for apple and cabbage, 50nM for pomegranate. The
      proposed FTO-AuNPs nanosensor can be used as a quantitative tool for rapid, on
      site detection of chlorpyrifos traces in real samples when miniaturized due to
      its excellent stability, sensitivity, and simplicity.

PMID- 29346075
TI  - Human Papillomavirus E6 interaction with cellular PDZ domain proteins modulates
      YAP nuclear localization.
AB  - HPV E6 oncoproteins associate with cellular PDZ proteins. In addition to
      previously identified cellular PDZ proteins, we found association of the HPV16 E6
      PBM with the Dystrophin Glycoprotein Complex, LRCC1, and SLC9A3R2. HPV18 E6 had
      additional associations when lysates from adenomatous cell lines were used
      including LRPPRC, RLGAPB, EIF3A, SMC2 and 3, AMOT, AMOTL1, and ARHGEF1; some of
      these cellular PDZ proteins are implicated in the regulation of the YAP1
      transcriptional co-activator. In keratinocytes, nuclear translocation of YAP1 was
      promoted by the complete HPV-16 genome, or by expression of the individual E6 or
      E7 oncoproteins; the activity of E6 required an intact PBM at the carboxy
      terminus. This work demonstrates that E6 association with cellular PDZ proteins
      promotes the nuclear localization of YAP1. The ability of E6 to promote the
      nuclear transport of YAP1 thus identifies an E6 activity that could contribute to
      the transformation of cells by E6.

PMID- 29346077
TI  - Three-dimensional graphene biointerface with extremely high sensitivity to single
      cancer cell monitoring.
AB  - We developed a three-dimensional biointerface of graphene-based electrical
      impedance sensor for metastatic cancer diagnosis at single-cell resolution.
      Compared with traditional impedance sensor with two-dimensional interface, the
      graphene biointerface mimiced the topography and somatotype features of cancer
      cells, achieving more comprehensive and thorough single cell signals in the three
      dimensional space. At the nodes of physiological behavior change of single cell,
      namely cell capture, adhesion, migration and proliferation, the collected
      electrical signals from graphene biointerface were about two times stronger than
      those from the two-dimensional gold interface due to the substantial increase in
      contact area and significant improvement of topographical interaction between
      cells and graphene electrode. Simultaneous CCD recording and electrical signal
      extraction from the entrapped single cell on the graphene biointerface enabled to
      investigate multidimensional cell-electrode interactions and predict cancerous
      stage and pathology.

PMID- 29346078
TI  - Long-term high air pollution exposure induced metabolic adaptations in traffic
      policemen.
AB  - OBJECTIVE: To assess the adverse physiological changes induced by long-term
      exposure to PM2.5. METHODS: Totally 183 traffic policemen and 88 office policemen
      as the control group, were enrolled in this study. The concentrations of PM2.5 in
      both the working places of traffic and office policemen were obtained. Detailed
      personal questionnaires and conventional laboratory tests including hematology,
      fasting blood glucose, blood lipids, liver, kidney, immunity and tumor-related
      markers were conducted on all participants of this study. RESULTS: A dose
      response relationship between the FBG, HDL-c and CEA values and the PM2.5
      exposure duration was observed. Multivariate analysis confirmed that one hour on
      duty outdoor per day for one year was associated with an increase in FBG of
      0.005% (95% CI: 0.0004% to 0.009%), CEA of 0.012% (95% CI: 0.006% to 0.017%), and
      a decrease in HDL-C of 0.001% (95% CI: 0.00034% to 0.002%). CONCLUSION: Long-term
      high air pollution exposure may lead to metabolism adaptation and it is likely
      involved in the development of cardiovascular disease and diabetes mellitus.

PMID- 29346079
TI  - A recognition mechanism study: Luminescent metal-organic framework for the
      detection of nitro-explosives.
AB  - This article presents a recognition mechanism for nitro-explosives by the
      luminescent metal-organic framework 1 (LMOF-1) with the aid of density functional
      theory (DFT) and time-dependent density functional theory (TDDFT). The behavior
      of hydrogen bonding between the LMOF-1 and nitro-explosives in the S1 state is
      closely associated with the fluorescence properties of the LMOF-1. In our
      research, we calculated the geometric configuration, 1H NMR and IR spectra of the
      Complex 2 formed by LMOF-1 and nitrobenzene in the S0 and S1 states. The results
      showed that the hydrogen bond in the S1 state was increased, which was
      unfavorable for the luminescence of LMOF-1. Furthermore, the fluorescence rate of
      LMOF-1 decreased after encapsulating nitrobenzene into it. These calculated
      results collectively suggest that LMOF-1 is a potential fluorescence sensor for
      the detection of nitro-explosives. This research was aiming to provide a better
      understanding of the recognition mechanism by LMOFs for nitro-explosives.

PMID- 29346080
TI  - New insight into the action of tryptanthrins against Plasmodium falciparum:
      Pharmacophore identification via a novel submolecular QSAR descriptor.
AB  - A new submolecular quantitative structure activity relationship (QSAR) descriptor
      was applied toward elucidating the anti-malarial pharmacophore of tryptanthrins,
      a class of compounds known for their anti-parasitic activities. The new
      descriptor is based on experimental and computational measurements of the
      tunneling barriers of individual lobes of the molecular orbitals. Lobe-by-lobe
      QSAR correlation plots revealed a single lobe of the LUMO to be strongly
      associated with tryptanthrin's anti-malarial activity. The correlation also
      showed a threshold behavior wherein barriers below a particular value show low
      IC50 values. Above the threshold, the correlation of IC50 vs the logarithm of the
      barrier is linear with R2 = 0.999. This barrier threshold may be applied as a
      design criterion for future tryptanthrin-based anti-malarial lead optimization.
      The new descriptor may be broadly applicable toward other molecular systems of
      interest, such as catalysts, pesticides, and herbicides. The authors have named
      the new descriptor: submolecular tunneling analysis of barriers (STAB).

PMID- 29346081
TI  - Reported balance confidence and movement reinvestment of younger knee replacement
      patients are more like younger healthy individuals, than older patients.
AB  - This study focused on differences between the rapidly growing younger (<65 years
      old) and older (>65 years old) total knee replacement (TKR) patients for measures
      of balance confidence, movement reinvestment, and functional mobility. Fifty-nine
      participants, including twenty-nine primary unilateral TKR patients (six months
      post-TKR) formed the four experimental groups: 1) Younger TKR Patient (YP), 2)
      Younger Control (YC), 3) Older TKR Patient (OP), and 4) Older Control (OC). The
      Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the
      Oxford Knee Score (OKS), Activities-specific Balance Confidence scale (ABC), the
      Movement-Specific Reinvestment Scale (MSRS), and the Timed Up and Go (TUG) test
      were measured. The YP group reported a significantly lower WOMAC score (p <
      0.001), and higher perceived knee joint function (p = 0.001), compared to the OP
      group. The YP group also reported significantly higher balance confidence (p <
      0.001) and less movement reinvestment (p = 0.001) than the OP group. TUG
      durations revealed that the YP group had significantly higher functional mobility
      compared to the OP group (p = 0.001). The YP group did not differ from the YC
      group across any of these measures (p > 0.05). These results identify a clear
      distinction between younger and older TKR patients for fall risk and TKR outcome,
      which argues that age should be a factor clinicians take into account when
      addressing the management and care of individuals recovering from TKR.

PMID- 29346082
TI  - Distal upper limb kinematics during functional everyday tasks.
AB  - Quantitative characterisation of upper limb motion allows the evaluation of the
      effect of pathology on functional task performance, potentially directing
      rehabilitation strategies. Movement patterns of the distal upper limb in healthy
      adults during functional tasks have not been extensively characterised. During
      five loaded functional tasks (drinking from a glass, pouring from a kettle,
      turning a handle, lifting a bag to a shelf, turning a key) the movement patterns
      were characterised using three-dimensional motion analysis with a minimal marker
      set in 16 healthy adults (10 M,6F, 27 (IQR:25-43)years). Joint angles reported
      include flexion/extension at the elbow and wrist, forearm supination/pronation
      and digits 2-5 metacarpophalangeal (MCP) joint flexion/extension. Additionally
      for the thumb the angle between the metacarpal of the thumb and the 2nd digit
      (Thumb base), the thumb MCP (Thumb MCP) and interphalangeal (Thumb IP) joint
      angles are presented. Durations of activities performed at self-selected
      comfortable speeds (3.36 (IQR:3.07,3.66)s turning a key to 6.20 (IQR:5.44,6.38)s
      drinking from a glass) are reported. The maximum joint angles used (median of
      participants' maxima) were 141 degrees  of elbow flexion, 116 degrees  forearm
      supination, 36 degrees  wrist extension, 56 degrees  Thumb base, 14 degrees 
      Thumb MCP flexion, 18 degrees  Thumb IP flexion, 85 degrees  MCP2-5 flexion. The
      tasks of drinking from a glass, lifting a bag to a shelf and turning a key
      appeared to have the least variation in performance, suggesting that these
      activities are better suited to be selected as standardized tasks for assessing
      the impact of pathology on movement than pouring from a kettle and turning a
      handle.

PMID- 29346083
TI  - Testing the cognitive catalyst model of rumination with explicit and implicit
      cognitive content.
AB  - BACKGROUND AND OBJECTIVES: The cognitive catalyst model posits that rumination
      and negative cognitive content, such as negative schema, interact to predict
      depressive affect. Past research has found support for this model using explicit
      measures of negative cognitive content such as self-report measures of trait self
      esteem and dysfunctional attitudes. The present study tested whether these
      findings would extend to implicit measures of negative cognitive content such as
      implicit self-esteem, and whether effects would depend on initial mood state and
      history of depression. METHOD: Sixty-one undergraduate students selected on the
      basis of depression history (27 previously depressed; 34 never depressed)
      completed explicit and implicit measures of negative cognitive content prior to
      random assignment to a rumination induction followed by a distraction induction
      or vice versa. Dysphoric affect was measured both before and after these
      inductions. RESULTS: Analyses revealed that explicit measures, but not implicit
      measures, interacted with rumination to predict change in dysphoric affect, and
      these interactions were further moderated by baseline levels of dysphoria.
      LIMITATIONS: Limitations include the small nonclinical sample and use of a self
      report measure of depression history. CONCLUSIONS: These findings suggest that
      rumination amplifies the association between explicit negative cognitive content
      and depressive affect primarily among people who are already experiencing sad
      mood.

PMID- 29346084
TI  - Effects of the road environment on the development of driver sleepiness in young
      male drivers.
AB  - Latent driver sleepiness may in some cases be masked by for example social
      interaction, stress and physical activity. This short-term modulation of
      sleepiness may also result from environmental factors, such as when driving in
      stimulating environments. The aim of this study is to compare two road
      environments and investigate how they affect driver sleepiness. Thirty young male
      drivers participated in a driving simulator experiment where they drove two
      scenarios: a rural environment with winding roads and low traffic density, and a
      suburban road with higher traffic density and a more built-up roadside
      environment. The driving task was essentially the same in both scenarios, i.e. to
      stay on the road, without much interaction with other road users. A 2 * 2 design,
      with the conditions rural versus suburban, and daytime (full sleep) versus night
      time (sleep deprived), was used. The results show that there were only minor
      effects of the road environment on subjective and physiological indicators of
      sleepiness. In contrast, there was an increase in subjective sleepiness, longer
      blink durations and increased EEG alpha content, both due to time on task and to
      night-time driving. The two road environments differed both in terms of the
      demand on driver action and of visual load, and the results indicate that action
      demand is the more important of the two factors. The notion that driver fatigue
      should be countered in a more stimulating visual environment such as in the city
      is thus more likely due to increased task demand rather than to a richer visual
      scenery. This should be investigated in further studies.

PMID- 29346085
TI  - Performance of the BioPlex 2200 HIV Ag-Ab assay for identifying acute HIV
      infection.
AB  - BACKGROUND: Assays that detect HIV antigen (Ag) and antibody (Ab) can be used to
      screen for HIV infection. OBJECTIVES: To compare the performance of the BioPlex
      2200 HIV Ag-Ab assay and two other Ag/Ab combination assays for detection of
      acute HIV infection. STUDY DESIGN: Samples were obtained from 24 individuals (18
      from the US, 6 from South Africa); these individuals were classified as having
      acute infection based on the following criteria: positive qualitative RNA assay;
      two negative rapid tests; negative discriminatory test. The samples were tested
      with the BioPlex assay, the ARCHITECT HIV Ag/Ab Combo test, the Bio-Rad GS HIV
      Combo Ag-Ab EIA test, and a viral load assay. RESULTS: Twelve (50.0%) of 24
      samples had RNA detected only ( > 40 to 13,476 copies/mL). Ten (43.5%) samples
      had reactive results with all three Ag/Ab assays, one sample was reactive with
      the ARCHITECT and Bio-Rad assays, and one sample was reactive with the Bio-Rad
      and BioPlex assays. The 11 samples that were reactive with the BioPlex assay had
      viral loads from 83,010 to >750,000 copies/mL; 9/11 samples were classified as Ag
      positive/Ab negative by the BioPlex assay. CONCLUSIONS: Detection of acute HIV
      infection was similar for the BioPlex assay and two other Ag/Ab assays. All three
      tests were less sensitive than a qualitative RNA assay and only detected HIV Ag
      when the viral load was high. The BioPlex assay detected acute infection in about
      half of the cases, and identified most of those infections as Ag positive/Ab
      negative.

PMID- 29346086
TI  - The dynamics of a serum steroid profile after stimulation with intravenous ACTH.
AB  - BACKGROUND: Stimulation with intravenous adrenocorticotropic hormone (ACTH) is a
      widely used diagnostic procedure to characterize the adrenocortical function.
      Currently, the response of serum cortisol, mainly quantified by immunoassays, is
      the only established read-out of this test. By using liquid chromatography
      coupled with mass spectrometry (LC-MS/MS) simultaneous determination of several
      steroids that respond to ACTH stimulation is now possible. The aim of this study
      was to further characterize the typical effect of exogenous ACTH (250 mg) on a LC
      MS/MS-serum steroid profile. METHODS: A set of 36 paired samples (pre-/post-IV
      ACTH) was investigated (age range 22-58, 26 female and 10 male individuals).
      Serum steroid profiling was performed using a LC-MS/MS method covering cortisol,
      cortisone, corticosterone, 11-deoxycortisol, 17-OH-progesterone and 11
      deoxycorticosterone. RESULTS: The concentrations of all measured steroids
      increased after stimulation with ACTH, except for cortisone. Serum
      corticosterone, 11-deoxycorticosterone and 11-deoxycortisol showed markedly more
      pronounced relative increases compared to cortisol. The strongest response was
      observed for corticosterone (15-fold median relative increase, compared to 1.4
      fold median increase of cortisol). CONCLUSION: Serum steroid profiling using LC
      MS/MS after stimulation with IV ACTH demonstrates highly dynamic response
      patterns. Further studies should address in particular serum corticosterone as a
      potential novel marker of biochemical stress response.

PMID- 29346087
TI  - A "not-for-profit" regulatory model for legal recreational cannabis: Insights
      from the regulation of gaming machine gambling in New Zealand.
AB  - A dozen or more regulatory frameworks have been proposed for legal cannabis but
      many of the "not-for-profit" options have yet to be developed in any detail,
      reducing the likelihood they will be seriously considered by policy makers. New
      Zealand's innovative "not-for-profit" regulatory regime for gaming machine
      gambling (i.e. "slot machines") has reversed the previous increase in gambling
      expenditure, empowered local councils to cap the number of gambling venues, and
      is unique in requiring the societies operating gaming machines to distribution
      40% of the gross expenditure from machines (i.e. $NZ 262 million in 2015) to
      community purposes (e.g. sports). However, the regime has been criticised for not
      addressing the concentration of gaming outlets in poorer communities, and not
      requiring grants to be allocated in the disadvantaged communities where outlets
      are located. There have also been cases of gaming societies providing community
      grants in exchange for direct or indirect benefits. In this paper we adapt this
      regulatory approach to a legal cannabis market. Under the proposed regime,
      licensed "not-for-profit" cannabis societies will be required to distribute 20%
      of cannabis sales to drug treatment and 20% to community purposes, including drug
      prevention. Grants must be allocated in the regions where cannabis sales are made
      and grant committees must be independent from cannabis societies. A 20% levy will
      be used to cover the wider health costs of cannabis use. A further 10% levy will
      be used to fund the regulator and evaluate the new regime. Local councils will
      have the power to decide how many, and where, cannabis retail outlets are
      located. Other important elements include a minimum price for cannabis, effective
      taxation of cannabis products, regulating CBD in cannabis products, higher
      taxation of traditional smoking products, advertising restricted to place-of
      sale, no internet sales, and restrictions on industry involvement in regulation
      making and research.

PMID- 29346088
TI  - Intense olfactory stimulation blocks seizures in an experimental model of
      epilepsy.
AB  - There are reports of patients whose epileptic seizures are prevented by means of
      olfactory stimulation. Similar findings were described in animal models of
      epilepsy, such as the electrical kindling of amygdala, where olfactory
      stimulation with toluene (TOL) suppressed seizures in most rats, even when the
      stimuli were 20% above the threshold to evoke seizures in already kindled
      animals. The Wistar Audiogenic Rat (WAR) strain is a model of tonic-clonic
      seizures induced by acute acoustic stimulation, although it also expresses limbic
      seizures when repeated acoustic stimulation occurs - a process known as
      audiogenic kindling (AK). The aim of this study was to evaluate whether or not
      the olfactory stimulation with TOL would interfere on the behavioral expression
      of brainstem (acute) and limbic (chronic) seizures in the WAR strain. For this,
      animals were exposed to TOL or saline (SAL) and subsequently exposed to acoustic
      stimulation in two conditions that generated: I) acute audiogenic seizures (only
      one acoustic stimulus, without previous seizure experience before of the odor
      test) and II) after AK (20 acoustic stimuli [2 daily] before of the protocol
      test). We observed a decrease in the seizure severity index of animals exposed
      only to TOL in both conditions, with TOL presented 20s before the acoustic
      stimulation in both protocols. These findings were confirmed by behavioral
      sequential analysis (neuroethology), which clearly indicated an exacerbation of
      clusters of specific behaviors such as exploration and grooming (self-cleaning),
      as well as significant decrease in the expression of brainstem and limbic
      seizures in response to TOL. Thus, these data demonstrate that TOL, a strong
      olfactory stimulus, has anticonvulsant properties, detected by the decrease of
      acute and AK seizures in WARs.

PMID- 29346089
TI  - Genererating a core cluster of Fasciola hepatica virulence and immunomodulation
      related genes using a comparative in silico approach.
AB  - A total of 71 virulence and immunomodulation-related transcripts (VIRs) of
      Fasciola hepatica have been previously proposed (Hacariz et al., 2015). In an
      attempt to further refine this cohort, an in silico meta analysis approach was
      carried out using publicly available sequence data of related liver flukes,
      Clonorchis sinensis and Opisthorchis viverrini. Data of both liver flukes were
      investigated in terms of sequential homology with data of non-parasitic
      organisms, pathogens and VIRs of F. hepatica, directional selection (Ka/Ks), and
      cytokine signaling relation (protein motif based). Some VIRs of F. hepatica
      [showing homology with immune receptors (for toll/interleukin-1, TGF-beta or TNF
      alpha), TGF-beta, TNF-alpha, CD147, or relation with suppressors of cytokine
      signaling/IKBKE 1 or stimulation of TGF-beta (through thrombospondin similarity)]
      were found to be orthologous with those of both C. sinensis and O. viverrini. The
      in silico analysis indicates that on the basis of genetic commonality, a total of
      30 VIRs of F. hepatica are highlighted as of foremost importance in the parasite
      evasion strategy, through controlling of host immune system. Findings in this
      study could be important to further enhance our understanding of the parasitic
      mechanisms and develop effective control strategies against F. hepatica and other
      related parasites.

PMID- 29346090
TI  - Fast 2D Complex Gabor Filter With Kernel Decomposition.
AB  - 2D complex Gabor filtering has found numerous applications in the fields of
      computer vision and image processing. Especially, in some applications, it is
      often needed to compute 2D complex Gabor filter bank consisting of filtering
      outputs at multiple orientations and frequencies. Although several approaches for
      fast Gabor filtering have been proposed, they focus primarily on reducing the
      runtime for performing filtering once at specific orientation and frequency. To
      obtain the Gabor filter bank, the existing methods are repeatedly applied with
      respect to multiple orientations and frequencies. In this paper, we propose a
      novel approach that efficiently computes the 2D complex Gabor filter bank by
      reducing the computational redundancy that arises when performing filtering at
      multiple orientations and frequencies. The proposed method first decomposes the
      Gabor kernel to allow a fast convolution with the Gaussian kernel in a separable
      manner. This enables reducing the runtime of the Gabor filter bank by reusing
      intermediate results computed at a specific orientation. By extending this idea,
      we also propose a fast approach for 2D localized sliding discrete Fourier
      transform that uses the Gaussian kernel in order to lend spatial localization
      ability as in the Gabor filter. Experimental results demonstrate that the
      proposed method runs faster than the state-of-the-art methods, while maintaining
      similar filtering quality.

PMID- 29346091
TI  - Plenoptic Image Motion Deblurring.
AB  - We propose a method to remove motion blur in a single light field captured with a
      moving plenoptic camera. Since motion is unknown, we resort to a blind
      deconvolution formulation, where one aims to identify both the blur point spread
      function and the latent sharp image. Even in the absence of motion, light field
      images captured by a plenoptic camera are affected by a non-trivial combination
      of both aliasing and defocus, which depends on the 3D geometry of the scene.
      Therefore, motion deblurring algorithms designed for standard cameras are not
      directly applicable. Moreover, many state of the art blind deconvolution
      algorithms are based on iterative schemes, where blurry images are synthesized
      through the imaging model. However, current imaging models for plenoptic images
      are impractical due to their high dimensionality. We observe that plenoptic
      cameras introduce periodic patterns that can be exploited to obtain highly
      parallelizable numerical schemes to synthesize images. These schemes allow
      extremely efficient GPU implementations that enable the use of iterative methods.
      We can then cast blind deconvolution of a blurry light field image as a
      regularized energy minimization to recover a sharp high-resolution scene texture
      and the camera motion. Furthermore, the proposed formulation can handle non
      uniform motion blur due to camera shake as demonstrated on both synthetic and
      real light field data.

PMID- 29346092
TI  - Hierarchical and Spatio-Temporal Sparse Representation for Human Action
      Recognition.
AB  - In this paper, we present a novel two-layer video representation for human action
      recognition employing hierarchical group sparse encoding technique and spatio
      temporal structure. In the first layer, a new sparse encoding method named
      locally consistent group sparse coding (LCGSC) is proposed to make full use of
      motion and appearance information of local features. LCGSC method not only
      encodes global layouts of features within the same video-level groups, but also
      captures local correlations between them, which obtains expressive sparse
      representations of video sequences. Meanwhile, two kinds of efficient location
      estimation models, namely an absolute location model and a relative location
      model, are developed to incorporate spatio-temporal structure into LCGSC
      representations. In the second layer, action-level group is established, where a
      hierarchical LCGSC encoding scheme is applied to describe videos at different
      levels of abstractions. On the one hand, the new layer captures higher order
      dependency between video sequences; on the other hand, it takes label information
      into consideration to improve discrimination of videos' representations. The
      superiorities of our hierarchical framework are demonstrated on several
      challenging datasets.

PMID- 29346093
TI  - Multipolarization Through-Wall Radar Imaging Using Low-Rank and Jointly-Sparse
      Representations.
AB  - Compressed sensing techniques have been applied to through-the-wall radar imaging
      (TWRI) and multipolarization TWRI for fast data acquisition and enhanced target
      localization. The studies so far in this area have either assumed effective wall
      clutter removal prior to image formation or performed signal estimation, wall
      clutter mitigation, and image formation independently. This paper proposes a low
      rank and sparse imaging model for jointly addressing the problem of wall clutter
      mitigation and image formation in multichannel TWRI. The proposed model exploits
      two important structures of through-wall radar signals: low-rank structure of the
      wall reflections and jointly-sparse structure among the different polarization
      images. The task of removing wall clutter and reconstructing multichannel images
      of the same scene behind-the-wall is formulated as a regularized least squares
      problem, where low-rank regularization is enforced for the wall components, and
      joint-sparsity penalty is imposed on channel images. To solve the optimization
      problem, an iterative algorithm based on the proximal gradient technique is
      introduced, which simultaneously estimates the wall interferences and yields
      multichannel images of the indoor targets. Experiments on real and simulated
      radar data are conducted under full measurements and compressive sensing
      scenarios. The results show that the proposed model is very effective at removing
      unwanted wall clutter and enhancing the stationary targets, even under
      considerable reduction in measurements.

PMID- 29346094
TI  - Reweighted Low-Rank Matrix Analysis With Structural Smoothness for Image
      Denoising.
AB  - In this paper, we develop a new low-rank matrix recovery algorithm for image
      denoising. We incorporate the total variation (TV) norm and the pixel range
      constraint into the existing reweighted low-rank matrix analysis to achieve
      structural smoothness and to significantly improve quality in the recovered
      image. Our proposed mathematical formulation of the low-rank matrix recovery
      problem combines the nuclear norm, TV norm, and norm, thereby allowing us to
      exploit the low-rank property of natural images, enhance the structural
      smoothness, and detect and remove large sparse noise. Using the iterative
      alternating direction and fast gradient projection methods, we develop an
      algorithm to solve the proposed challenging non-convex optimization problem. We
      conduct extensive performance evaluations on single-image denoising, hyper
      spectral image denoising, and video background modeling from corrupted images.
      Our experimental results demonstrate that the proposed method outperforms the
      state-of-the-art low-rank matrix recovery methods, particularly for large random
      noise. For example, when the density of random sparse noise is 30%, for single
      image denoising, our proposed method is able to improve the quality of the
      restored image by up to 4.21 dB over existing methods.

PMID- 29346095
TI  - Feature Map Quality Score Estimation Through Regression.
AB  - Understanding the visual quality of a feature map plays a significant role in
      many active vision applications. Previous works mostly rely on object-level
      features, such as compactness, to estimate the quality score of a feature map.
      However, the compactness is leveraged on feature maps produced by salient object
      detection techniques where the maps tend to be compact. As a result, the
      compactness feature fails when the feature maps are blurry (e.g., fixation maps).
      In this paper, we regard the process of estimating the quality score of feature
      maps, specifically fixation maps, as a regression problem. After extracting
      several local, global, geometric, and positional characteristic features from a
      feature map, a model is learned using a random forest regressor to estimate the
      quality score of any unseen feature map. Our model is specifically tailored to
      estimate the quality of three types of maps: bottom-up, target, and contextual
      feature maps. These maps are produced for a large benchmark fixation data set of
      more than 900 challenging outdoor images. We demonstrate that our approach
      provides an accurate estimate of the quality of the abovementioned feature maps
      compared to the groundtruth data. In addition, we show that our proposed approach
      is useful in feature map integration for predicting human fixation. Instead of
      naively integrating all three feature maps when predicting human fixation, our
      proposed approach dynamically selects the best feature map with the highest
      estimated quality score on an individual image basis, thereby improving the
      fixation prediction accuracy.

PMID- 29346096
TI  - Iterative Graph Seeking for Object Tracking.
AB  - To effectively solve the challenges in object tracking, such as large deformation
      and severe occlusion, many existing methods use graph-based models to capture
      target part relations, and adopt a sequential scheme of target part selection,
      part matching, and state estimation. However, such methods have two major
      drawbacks: 1) inaccurate part selection leads to performance deterioration of
      part matching and state estimation and 2) there are insufficient effective global
      constraints for local part selection and matching. In this paper, we propose a
      new object tracking method based on iterative graph seeking, which integrate
      target part selection, part matching, and state estimation using a unified energy
      minimization framework. Our method also incorporates structural information in
      local parts variations using the global constraint. We devise an alternative
      iteration scheme to minimize the energy function for searching the most plausible
      target geometric graph. Experimental results on several challenging benchmarks
      (i.e., VOT2015, OTB2013, and OTB2015) demonstrate improved performance and
      robustness in comparison with existing algorithms.

PMID- 29346097
TI  - Change Detection in Heterogenous Remote Sensing Images via Homogeneous Pixel
      Transformation.
AB  - The change detection in heterogeneous remote sensing images remains an important
      and open problem for damage assessment. We propose a new change detection method
      for heterogeneous images (i.e., SAR and optical images) based on homogeneous
      pixel transformation (HPT). HPT transfers one image from its original feature
      space (e.g., gray space) to another space (e.g., spectral space) in pixel-level
      to make the pre-event and post-event images represented in a common space for the
      convenience of change detection. HPT consists of two operations, i.e., the
      forward transformation and the backward transformation. In forward
      transformation, for each pixel of pre-event image in the first feature space, we
      will estimate its mapping pixel in the second space corresponding to post-event
      image based on the known unchanged pixels. A multi-value estimation method with
      noise tolerance is introduced to determine the mapping pixel using -nearest
      neighbors technique. Once the mapping pixels of pre-event image are available,
      the difference values between the mapping image and the post-event image can be
      directly calculated. After that, we will similarly do the backward transformation
      to associate the post-event image with the first space, and one more difference
      value for each pixel will be obtained. Then, the two difference values are
      combined to improve the robustness of detection with respect to the noise and
      heterogeneousness (modality difference) of images. Fuzzy-c means clustering
      algorithm is employed to divide the integrated difference values into two
      clusters: changed pixels and unchanged pixels. This detection results may contain
      some noisy regions (i.e., small error detections), and we develop a spatial
      neighbor-based noise filter to further reduce the false alarms and missing
      detections using belief functions theory. The experiments for change detection
      with real images (e.g., SPOT, ERS, and NDVI) during a flood in U.K. are given to
      validate the effectiveness of the proposed method.

PMID- 29346098
TI  - Region-Based Prediction for Image Compression in the Cloud.
AB  - Thanks to the increasing number of images stored in the cloud, external image
      similarities can be leveraged to efficiently compress images by exploiting inter
      images correlations. In this paper, we propose a novel image prediction scheme
      for cloud storage. Unlike current state-of-the-art methods, we use a semi-local
      approach to exploit inter-image correlation. The reference image is first
      segmented into multiple planar regions determined from matched local features and
      super-pixels. The geometric and photometric disparities between the matched
      regions of the reference image and the current image are then compensated.
      Finally, multiple references are generated from the estimated compensation models
      and organized in a pseudo-sequence to differentially encode the input image using
      classical video coding tools. Experimental results demonstrate that the proposed
      approach yields significant rate-distortion performance improvements compared
      with the current image inter-coding solutions such as high efficiency video
      coding.

PMID- 29346099
TI  - Cell Membrane Tracking in Living Brain Tissue Using Differential Interference
      Contrast Microscopy.
AB  - Differential interference contrast (DIC) microscopy is widely used for observing
      unstained biological samples that are otherwise optically transparent. Combining
      this optical technique with machine vision could enable the automation of many
      life science experiments; however, identifying relevant features under DIC is
      challenging. In particular, precise tracking of cell boundaries in a thick ( )
      slice of tissue has not previously been accomplished. We present a novel
      deconvolution algorithm that achieves the state-of-the-art performance at
      identifying and tracking these membrane locations. Our proposed algorithm is
      formulated as a regularized least squares optimization that incorporates a
      filtering mechanism to handle organic tissue interference and a robust edge
      sparsity regularizer that integrates dynamic edge tracking capabilities. As a
      secondary contribution, this paper also describes new community infrastructure in
      the form of a MATLAB toolbox for accurately simulating DIC microscopy images of
      in vitro brain slices. Building on existing DIC optics modeling, our simulation
      framework additionally contributes an accurate representation of interference
      from organic tissue, neuronal cell-shapes, and tissue motion due to the action of
      the pipette. This simulator allows us to better understand the image statistics
      (to improve algorithms), as well as quantitatively test cell segmentation and
      tracking algorithms in scenarios, where ground truth data is fully known.

PMID- 29346100
TI  - Improving Color Constancy in an Ambient Light Environment Using the Phong
      Reflection Model.
AB  - We present a physics-based illumination estimation approach explicitly designed
      to handle natural images under ambient light. Existing physics-based color
      constancy methods are theoretically perfect but do not handle real-world images
      well because the majority of these methods assume a single illuminant. Therefore,
      specular pixels selected using existing methods produce estimated dichromatic
      lines that are thick or curvilinear in the presence of ambient light, thus
      generating significant errors. Based on the Phong reflection model, we show that
      a group of specular pixels on a uniformly colored object, although they are
      subject to intensity thresholding, produce a unique dichromatic line length
      depending on the geometry of each image path. Assuming that the longest
      dichromatic line is the most desirable when estimating the chromaticity of an
      illuminant, ambient-robust specular pixels are also found on the same path on
      which the longest dichromatic line segment is generated. Therefore, we propose a
      method to find the optimal image path in which the specular pixels produce the
      longest dichromatic line. Even though the number of collected specular pixels is
      reduced using the proposed method, they are proven to be more accurate when
      determining the illuminant chromaticity even in the existing methods. Experiments
      with an established benchmark data set and a self-produced image set find that
      the proposed method is better able to locate the illuminant chromaticity compared
      with the state-of-the-art color constancy methods.

PMID- 29346101
TI  - Stacked Denoising Tensor Auto-Encoder for Action Recognition With Spatiotemporal
      Corruptions.
AB  - Spatially or temporally corrupted action videos are impractical for recognition
      via vision or learning models. It usually happens when streaming data are
      captured from unintended moving cameras, which bring occlusion or camera
      vibration and accordingly result in arbitrary loss of spatiotemporal information.
      In reality, it is intractable to deal with both spatial and temporal corruptions
      at the same time. In this paper, we propose a coupled stacked denoising tensor
      auto-encoder (CSDTAE) model, which approaches this corruption problem in a divide
      and-conquer fashion by jointing both the spatial and temporal schemes together.
      In particular, each scheme is a SDTAE designed to handle either spatial or
      temporal corruption, respectively. SDTAE is composed of several blocks, each of
      which is a denoising tensor auto-encoder (DTAE). Therefore, CSDTAE is designed
      based on several DTAE building blocks to solve the spatiotemporal corruption
      problem simultaneously. In one DTAE, the video features are represented as a high
      order tensor to preserve the spatiotemporal structure of data, where the temporal
      and spatial information are processed separately in different hidden layers via
      tensor unfolding. In summary, DTAE explores the spatial and temporal structure of
      the tensor representation, and SDTAE handles different corrupted ratios
      progressively to extract more discriminative features. CSDTAE couples the
      temporal and spatial corruptions of the same data through a thorough step-by-step
      procedure based on canonical correlation analysis, which integrates the two sub
      problems into one problem. The key point is solving the spatiotemporal corruption
      in one model by considering them as noises in either spatial or temporal
      direction. Extensive experiments on three action data sets demonstrate the
      effectiveness of our model, especially when large volumes of corruption in the
      video.

PMID- 29346102
TI  - Impedance Measures During in vitro Cochlear Implantation Predict Array
      Positioning.
AB  - OBJECTIVE: Improper electrode placement during cochlear implant (CI) insertion
      can adversely affect speech perception outcomes. However, the intraoperative
      methods to determine positioning are limited. Because measures of electrode
      impedance can be made quickly, the goal of this study was to assess the
      relationship between CI impedance and proximity to adjacent structures. METHODS:
      An Advanced Bionics CI array was inserted into a clear, plastic cochlea one
      electrode contact at a time in a saline bath (nine trials). At each insertion
      depth, response to biphasic current pulses was used to calculate access
      resistance (Ra), polarization resistance (Rp), and polarization capacitance (Cp).
      These measures were correlated to actual proximity as assessed by microscopy
      using linear regression models. RESULTS: Impedance increased with insertion depth
      and proximity to the inner wall. Specifically, Ra increased, Cp decreased, and Rp
      slightly increased. Incorporating all impedance measures afforded a prediction
      model (r = 0.88) while optimizing for sub-mm positioning afforded a model with
      78.3% specificity. CONCLUSION: Impedance in vitro greatly changes with electrode
      insertion depth and proximity to adjacent structures in a predicable manner.
      SIGNIFICANCE: Assessing proximity of the CI to adjacent structures is a
      significant first step in qualifying the electrode-neural interface. This
      information should aid in CI fitting, which should help maximize hearing and
      speech outcomes with a CI. Additionally, knowledge of the relationship between
      impedance and positioning could have utility in other tissue implants in the
      brain, retina, or spinal cord.

PMID- 29346103
TI  - WaveDec: A Wavelet Approach to Identify Both Shared and Individual Patterns of
      Copy-Number Variations.
AB  - : Copy-number variations (CNVs) are associated with complex diseases and
      particular tumor types. Array-based comparative genomic hybridization (aCGH) is a
      common approach for the detection of CNVs. Traditional CNV detection methods for
      multiple aCGH samples mainly use batch samples to find common variations, not
      accounting for the individual characteristics of each sample. Accurately
      differentiating both the commonly shared and the individual CNV patterns is
      pivotal to identify cell populations, or to distinguish cell growth (as in
      cancer) from invasion of new cells. Our preliminary results have now demonstrated
      that both the shared and individual CNV patterns have distinctive characteristics
      after wavelet transform. METHODS: To exploit these characteristics, we propose to
      formulate a quadratic data-separation problem within the wavelet space to
      discriminate the shared and individual CNVs from raw data. We have elaborated a
      numerical solution and shown that the solution can be obtained by solving
      decoupled subproblems. By this approach, computational costs can be limited,
      enabling efficient application in the analysis of large sequencing datasets.
      RESULTS: The advantages of our proposed method, called WaveDec, have been
      demonstrated by comparison with popular CNV-detection methods using synthetic and
      empirical aCGH data. The performance of WaveDec was further validated by
      experiments with single-cell-sequencing data. CONCLUSION: WaveDec can
      successfully differentiate shared and individual patterns, and performs well even
      in data contaminated with high levels of noise. SIGNIFICANCE: Both the shared and
      individual patterns can be uniquely characterized as well as effectively
      decomposed within the wavelet space.

PMID- 29346104
TI  - Characterization and Modeling of Tissue Thermal Conductivity During an
      Electrosurgical Joining Process.
AB  - Electrosurgical vessel joining is commonly performed in surgical procedures to
      maintain hemostasis. This process requires elevated temperature to denature the
      tissue and while compression is applied, the tissue can be joined together. The
      elevated temperature can cause thermal damages to the surrounding tissues. In
      order to minimize these damages, it is critical to understand how the tissue
      properties change and how that affects the thermal spread. The purpose of this
      study is to investigate the changes of tissue thermal conductivity and how the
      changes correlate to thermal dose during the joining process. We propose a hybrid
      method combining experimental measurement with inverse heat transfer analysis to
      determine thermal conductivity of thin tissue sample. Porcine aorta arterial
      tissues were used to investigate tissue thermal conductivity with variable
      thermal dose. Different joining times were used to create different amounts of
      thermal dose. A 36% decrease in tissue thermal conductivity was found when the
      thermal dose reaches the threshold for second-degree burn. When thermal dose is
      beyond the threshold of third-degree burn, the tissue thermal conductivity does
      not decrease significantly. A regression model was also developed and can be used
      to predict tissue thermal conductivity based on the thermal dose.

PMID- 29346106
TI  - Spatial Position Measurement System for Surgical Navigation Using 3-D Image
      Marker-Based Tracking Tools With Compact Volume.
AB  - We develop a spatial position measurement system using three-dimensional (3-D)
      image marker-based tracking tools targeted at surgical navigation in minimally
      invasive surgery. We generate 3-D image markers with spatial information encoded
      to 2-D images, design tracking tools with the 3-D image markers, and analyze the
      tracking tools' theoretical spatial errors, which are primarily limited by the
      spatial distribution of reconstructed fiducial 3-D markers. A pattern analysis
      based positional measurement algorithm is developed to calculate the tool's
      spatial information using its spatial configuration. Evaluation experiments were
      conducted to demonstrate the accuracy and effectiveness of the proposed system.
      Furthermore, surgical navigation feasibility studies were performed. With a
      patient-image registration algorithm, a navigation interface that shows
      preoperative medical data and intraoperative information about the tool can
      intuitively and accurately assist surgeons. The results demonstrate that the
      proposed tracking tools, which have compact volume and spatial positional
      information, are of potential use in minimally invasive surgery in a limited
      space.

PMID- 29346105
TI  - Automated Detection of Postictal Generalized EEG Suppression.
AB  - Although there is no strict consensus, some studies have reported that Postictal
      generalized EEG suppression (PGES) is a potential electroencephalographic (EEG)
      biomarker for risk of sudden unexpected death in epilepsy (SUDEP). PGES is an
      epoch of EEG inactivity after a seizure, and the detection of PGES in clinical
      data is extremely difficult due to artifacts from breathing, movement and muscle
      activity that can adversely affect the quality of the recorded EEG data. Even
      clinical experts visually interpreting the EEG will have diverse opinions on the
      start and end of PGES for a given patient. The development of an automated EEG
      suppression detection tool can assist clinical personnel in the review and
      annotation of seizure files, and can also provide a standard for quantifying PGES
      in large patient cohorts, possibly leading to further clarification of the role
      of PGES as a biomarker of SUDEP risk. In this paper, we develop an automated
      system that can detect the start and end of PGES using frequency domain features
      in combination with boosting classification algorithms. The average power for
      different frequency ranges of EEG signals are extracted from the prefiltered
      recorded signal using the fast fourier transform and are used as the feature set
      for the classification algorithm. The underlying classifiers for the boosting
      algorithm are linear classifiers using a logistic regression model. The tool is
      developed using 12 seizures annotated by an expert then tested and evaluated on
      another 20 seizures that were annotated by 11 experts.

PMID- 29346107
TI  - Brain MR Image Restoration Using an Automatic Trilateral Filter With GPU-Based
      Acceleration.
AB  - OBJECTIVE: Noise reduction in brain magnetic resonance (MR) images has been a
      challenging and demanding task. This study develops a new trilateral filter that
      aims to achieve robust and efficient image restoration. METHODS: Extended from
      the bilateral filter, the proposed algorithm contains one additional intensity
      similarity funct-ion, which compensates for the unique characteristics of noise
      in brain MR images. An entropy function adaptive to intensity variations is
      introduced to regulate the contributions of the weighting components. To hasten
      the computation, parallel computing based on the graphics processing unit (GPU)
      strategy is explored with emphasis on memory allocations and thread
      distributions. To automate the filtration, image texture feature analysis
      associated with machine learning is investigated. Among the 98 candidate
      features, the sequential forward floating selection scheme is employed to acquire
      the optimal texture features for regularization. Subsequently, a two-stage
      classifier that consists of support vector machines and artificial neural
      networks is established to predict the filter parameters for automation. RESULTS:
      A speedup gain of 757 was reached to process an entire MR image volume of 256 *
      256 * 256 pixels, which completed within 0.5 s. Automatic restoration results
      revealed high accuracy with an ensemble average relative error of 0.53 +/- 0.85%
      in terms of the peak signal-to-noise ratio. CONCLUSION: This self-regulating
      trilateral filter outperformed many state-of-the-art noise reduction methods both
      qualitatively and quantitatively. SIGNIFICANCE: We believe that this new image
      restoration algorithm is of potential in many brain MR image processing
      applications that require expedition and automation.

PMID- 29346108
TI  - Modeling of Electroporation Induced by Pulsed Electric Fields in Irregularly
      Shaped Cells.
AB  - During the past decades, the poration of cell membrane induced by pulsed electric
      fields has been widely investigated. Since the basic mechanisms of this process
      have not yet been fully clarified, many research activities are focused on the
      development of suitable theoretical and numerical models. To this end, a
      nonlinear, nonlocal, dispersive, and space-time numerical algorithm has been
      developed and adopted to evaluate the transmembrane voltage and pore density
      along the perimeter of realistic irregularly shaped cells. The presented model is
      based on the Maxwell's equations and the asymptotic Smoluchowski's equation
      describing the pore dynamics. The dielectric dispersion of the media forming the
      cell has been modeled by using a general multirelaxation Debye-based formulation.
      The irregular shape of the cell is described by using the Gielis' superformula.
      Different test cases pertaining to red blood cells, muscular cells, cell in
      mitosis phase, and cancer-like cell have been investigated. For each type of
      cell, the influence of the relevant shape, the dielectric properties, and the
      external electric pulse characteristics on the electroporation process has been
      analyzed. The numerical results demonstrate that the proposed model is an
      efficient numerical tool to study the electroporation problem in arbitrary-shaped
      cells.

PMID- 29346109
TI  - Endocardial Energy Harvesting by Electromagnetic Induction.
AB  - OBJECTIVE: cardiac pacemakers require regular medical follow-ups to ensure proper
      functioning. However, device replacements due to battery depletion are common and
      account for ~25% of all implantation procedures. Furthermore, conventional
      pacemakers require pacemaker leads which are prone to fractures, dislocations or
      isolation defects. The ensuing surgical interventions increase risks for the
      patients and costs that need to be avoided. METHODS: in this study, we present a
      method to harvest energy from endocardial heart motions. We developed a novel
      generator, which converts the heart's mechanical into electrical energy by
      electromagnetic induction. A mathematical model has been introduced to identify
      design parameters strongly related to the energy conversion efficiency of heart
      motions and fit the geometrical constraints for a miniaturized transcatheter
      deployable device. The implemented final design was tested on the bench and in
      vivo. RESULTS: the mathematical model proved an accurate method to estimate the
      harvested energy. For three previously recorded heart motions, the model
      predicted a mean output power of 14.5, 41.9, and 16.9 MUW. During an animal
      experiment, the implanted device harvested a mean output power of 0.78 and 1.7
      MUW at a heart rate of 84 and 160 bpm, respectively. CONCLUSION: harvesting
      kinetic energy from endocardial motions seems feasible. Implanted at an
      energetically favorable location, such systems might become a welcome alternative
      to extend the lifetime of cardiac implantable electronic device. SIGNIFICANCE:
      the presented endocardial energy harvesting concept has the potential to turn
      pacemakers into battery- and leadless systems and thereby eliminate two major
      drawbacks of contemporary systems.

PMID- 29346110
TI  - A Three-Dimensional Arrayed Microfluidic Blood-Brain Barrier Model With
      Integrated Electrical Sensor Array.
AB  - OBJECTIVE: The blood-brain barrier (BBB) poses a unique challenge to the
      development of therapeutics against neurological disorders due to its impermeabi
      lity to most of the chemical compounds. Most in vitro BBB models have limitations
      in mimicking in vivo conditions and functions. Here, we show a co-culture
      microfluidic BBB-on-a-chip that provides interactions between neurovascular
      endothelial cells and neuronal cells across a porous polycarbonate membrane,
      which better mimics the in vivo conditions, as well as allows in vivo level shear
      stress to be applied. METHODS: A 4 * 4 intersecting microchannel array forms 16
      BBB sites on a chip, with a multielectrode array integrated to measure the
      transendothelial electrical resistance (TEER) from all 16 different sites, which
      allows label-free real-time analysis of the barrier function. Primary mouse
      endothelial cells and primary astrocytes were co-cultured in the chip while
      applying in vivo level shear stress. The chip allows the barrier function to be
      analyzed through TEER measurement, dextran permeability, as well as
      immunostaining. RESULTS: Co-culture between astrocytes and endothelial cells, as
      well as in vivo level shear stress applied, led to the formation of tighter
      junctions and significantly lower barrier permeability. Moreover, drug testing
      with histamine showed increased permeability when using only endothelial cells
      compared to almost no change when using co-culture. CONCLUSION: Results show that
      the developed BBB chip more closely mimics the in vivo BBB environment.
      SIGNIFICANCE: The developed multisite BBB chip is expected to be used for
      screening drug by more accurately predicting their permeability through BBB as
      well as their toxicity.

PMID- 29346111
TI  - Single-Scan High-Resolution 2-D $J$ -Resolved Spectroscopy in Inhomogeneous
      Magnetic Fields.
AB  - OBJECTIVE: A method is proposed to obtain high-resolution 2-D -resolved nuclear
      magnetic resonance (NMR) spectra in inhomogeneous magnetic fields. METHODS: The
      proposed experiment enables the acquisition of an entire 2-D spectrum in a single
      scan by utilizing intermolecular double-quantum coherences and the spatial
      encoding of NMR observables. RESULTS: Chemical shifts, coupling constants, and
      multiplet patterns are recovered even when field inhomogeneities are severe
      enough to completely obscure conventional NMR spectra. After intentional
      deshimming to yield inhomogeneous magnetic fields, the method was demonstrated on
      ethyl 3-bromoproprionate in acetone and on a complex mixture of organic
      compounds. To illustrate the technique's applicability to biological samples with
      intrinsic magnetic field inhomogeneities arising from macroscopic magnetic
      susceptibility variations, we performed the experiment on a pig bone marrow
      sample. CONCLUSION: Our results show that the new method is a fast and effective
      tool for studying complex chemical mixtures and biological tissues. SIGNIFICANCE:
      The method could potentially be useful for real-time in vivo NMR studies.

PMID- 29346112
TI  - Numerical Model Reduction for the Prediction of Interface Pressure Applied by
      Compression Bandages on the Lower Leg.
AB  - OBJECTIVE: To develop a new method for the prediction of interface pressure
      applied by medical compression bandages. METHODS: A finite element simulation of
      bandage application was designed, based on patient-specific leg geometries. For
      personalized interface pressure prediction, a model reduction approach was
      proposed, which included the parametrization of the leg geometry. Pressure values
      computed with this reduced model were then confronted to experimental pressure
      values. RESULTS: The most influencing parameters were found to be the bandage
      tension, the skin-to-bandage friction coefficient and the leg morphology. Thanks
      to the model reduction approach, it was possible to compute interface pressure as
      a linear combination of these parameters. The pressures computed with this
      reduced model were in agreement with experimental pressure values measured on 66
      patients' legs. CONCLUSION: This methodology helps to predict patient-specific
      interface pressure applied by compression bandages within a few minutes whereas
      it would take a few days for the numerical simulation. The results of this method
      show less bias than Laplace's Law, which is for now the only other method for
      interface pressure computation.

PMID- 29346113
TI  - Uncertainty in Limb Configuration Makes Minimal Contribution to Errors Between
      Observed and Predicted Forces in a Musculoskeletal Model of the Rat Hindlimb.
AB  - Subject-specific musculoskeletal models are increasingly used in biomedical
      applications to predict endpoint forces due to muscle activation, matching
      predicted forces to experimentally observed forces at a specific limb
      configuration. However, it is difficult to precisely measure the limb
      configuration at which these forces are observed. The consequent uncertainty in
      limb configuration might contribute to errors in model predictions. We therefore
      evaluated how uncertainties in limb configuration measurement contributed to
      errors in force prediction, using data from in vivo measurements in the rat
      hindlimb. We used a data-driven approach to estimate the uncertainty in estimated
      limb configuration and then used this configuration uncertainty to evaluate the
      consequent uncertainty in force predictions, using Monte Carlo simulations. We
      used subject-specific models of joint structures (i.e., centers and axes of
      rotation) in order to estimate limb configurations for each animal. The standard
      deviation of the distribution of predicted force directions resulting from
      configuration uncertainty was small, ranging between 0.27 degrees  and 3.05
      degrees  across muscles. For most muscles, this standard deviation was
      considerably smaller than the error between observed and predicted forces
      (between 0.57 degrees  and 70.96 degrees ), suggesting that uncertainty in limb
      configuration could not explain inaccuracies in model predictions. Instead, our
      results suggest that inaccuracies in muscle model parameters, most likely in
      parameters specifying muscle moment arms, are the main source of prediction
      errors by musculoskeletal models in the rat hindlimb.

PMID- 29346114
TI  - OR.NET: a service-oriented architecture for safe and dynamic medical device
      interoperability.
AB  - Modern surgical departments are characterized by a high degree of automation
      supporting complex procedures. It recently became apparent that integrated
      operating rooms can improve the quality of care, simplify clinical workflows, and
      mitigate equipment-related incidents and human errors. Particularly using
      computer assistance based on data from integrated surgical devices is a promising
      opportunity. However, the lack of manufacturer-independent interoperability often
      prevents the deployment of collaborative assistive systems. The German flagship
      project OR.NET has therefore developed, implemented, validated, and standardized
      concepts for open medical device interoperability. This paper describes the
      universal OR.NET interoperability concept enabling a safe and dynamic
      manufacturer-independent interconnection of point-of-care (PoC) medical devices
      in the operating room and the whole clinic. It is based on a protocol
      specifically addressing the requirements of device-to-device communication, yet
      also provides solutions for connecting the clinical information technology (IT)
      infrastructure. We present the concept of a service-oriented medical device
      architecture (SOMDA) as well as an introduction to the technical specification
      implementing the SOMDA paradigm, currently being standardized within the IEEE
      11073 service-oriented device connectivity (SDC) series. In addition, the Session
      concept is introduced as a key enabler for safe device interconnection in highly
      dynamic ensembles of networked medical devices; and finally, some security
      aspects of a SOMDA are discussed.

PMID- 29346115
TI  - Mitochondrial dysfunction: a key player in the pathogenesis of cardiovascular
      diseases linked to air pollution.
AB  - Air pollution has become an environmental burden with regard to non-communicable
      diseases, particularly heart disease. It has been reported that air pollution can
      accelerate the development of heart failure and atrial fibrillation. Air
      pollutants encompass various particulate matters (PMs), which change the blood
      composition and heart rate and eventually leads to cardiac failure by triggering
      atherosclerotic plaque ruptures or by developing irreversible ischemia. A series
      of major epidemiological and observational studies have established the noxious
      effect of air pollutants on cardiovascular diseases (CVD), but the underlying
      molecular mechanisms of its susceptibility and the pathological disease events
      remain largely elusive and are predicted to be initiated in the cell organelle.
      The basis of this belief is that mitochondria are one of the major targets of
      environmental toxicants that can damage mitochondrial morphology, function and
      its DNA (manifested in non-communicable diseases). In this article, we review the
      literature related to air pollutants that adversely affect the progression of CVD
      and that target mitochondrial morphological and functional activities and how
      mitochondrial DNA (mtDNA) copy number variation, which reflects the airborne
      oxidant-induced cell damage, correlates with heart failure. We conclude that
      environmental health assessment should focus on the cellular/circulatory
      mitochondrial functional copy number status, which can predict the outcome of
      CVD.

PMID- 29346116
TI  - 4D computed tomography scans for conformal thoracic treatment planning: is a
      single scan sufficient to capture thoracic tumor motion?
AB  - Four dimensional computed tomography (4DCT) scans are routinely used in radiation
      therapy to determine the internal treatment volume for targets that are moving
      (e.g. lung tumors). The use of these studies has allowed clinicians to create
      target volumes based upon the motion of the tumor during the imaging study. The
      purpose of this work is to determine if a target volume based on a single 4DCT
      scan at simulation is sufficient to capture thoracic motion. Phantom studies were
      performed to determine expected differences between volumes contoured on 4DCT
      scans and those on the evaluation CT scans (slow scans). Evaluation CT scans
      acquired during treatment of 11 patients were compared to the 4DCT scans used for
      treatment planning. The images were assessed to determine if the target remained
      within the target volume determined during the first 4DCT scan. A total of 55
      slow scans were compared to the 11 planning 4DCT scans. Small differences were
      observed in phantom between the 4DCT volumes and the slow scan volumes, with a
      maximum of 2.9%, that can be attributed to minor differences in contouring and
      the ability of the 4DCT scan to adequately capture motion at the apex and base of
      the motion trajectory. Larger differences were observed in the patients studied,
      up to a maximum volume difference of 33.4%. These results demonstrate that a
      single 4DCT scan is not adequate to capture all thoracic motion throughout
      treatment.

PMID- 29346118
TI  - Mycobacterium avium complex pulmonary disease: new epidemiology and management
      concepts.
AB  - PURPOSE OF REVIEW: The prevalence of Mycobacterium avium complex (MAC)-related
      pulmonary disease has been increasing because of environmental factors, changes
      in organism virulence, and evolving host susceptibility. Treatment is often
      complicated by adverse effects, development of drug resistance, and refractory
      disease, with recurrence rates as high as 25-45%. RECENT FINDINGS: Aerosolization
      of water, soil, or dusts are the likely sources of MAC-related pulmonary disease
      in susceptible individuals. The management of MAC-related pulmonary disease
      requires a multimodality approach, including antimicrobial therapy in appropriate
      patients, employment of mucus clearance techniques, instituting changes in the
      individual's home environment and personal habits to reduce environmental
      exposure to MAC, prevention of reflux, and maintenance of a healthy body weight.
      When the standard treatment for MAC-related pulmonary disease is not possible
      because of drug intolerance, antibiotic resistance, or progression of disease,
      second-line agents such as inhaled amikacin, clofazimine, bedaquiline, and
      delamanid must be considered, despite limited experience and few studies to guide
      their use. SUMMARY: Individuals who have proven to be susceptible to MAC-related
      pulmonary disease should institute measures to reduce exposure to environmental
      sources of infection. Further research is needed to assess the impact of such
      preventive strategies on the incidence of new infection and disease recurrence.
      The efficacy of new medications for MAC-related pulmonary disease and their use
      in different combinations also requires further study.

PMID- 29346117
TI  - The deubiquitinase USP9X regulates FBW7 stability and suppresses colorectal
      cancer.
AB  - The tumor suppressor FBW7 targets oncoproteins such as c-MYC for ubiquitylation
      and is mutated in several human cancers. We noted that in a substantial
      percentage of colon cancers, FBW7 protein is undetectable despite the presence of
      FBW7 mRNA. To understand the molecular mechanism of FBW7 regulation in these
      cancers, we employed proteomics and identified the deubiquitinase (DUB) USP9X as
      an FBW7 interactor. USP9X antagonized FBW7 ubiquitylation, and Usp9x deletion
      caused Fbw7 destabilization. Mice lacking Usp9x in the gut showed reduced
      secretory cell differentiation and increased progenitor proliferation,
      phenocopying Fbw7 loss. In addition, Usp9x inactivation impaired intestinal
      regeneration and increased tumor burden in colitis-associated intestinal cancer.
      c-Myc heterozygosity abrogated increased progenitor proliferation and tumor
      burden in Usp9x-deficient mice, suggesting that Usp9x suppresses tumor formation
      by regulating Fbw7 protein stability and thereby reducing c-Myc. Thus, we
      identify a tumor suppressor mechanism in the mammalian intestine that arises from
      the posttranslational regulation of FBW7 by USP9X independent of somatic FBW7
      mutations.

PMID- 29346119
TI  - The role of tedizolid in skin and soft tissue infections.
AB  - PURPOSE OF REVIEW: Tedizolid is a second-generation oxazolidinone with activity
      against Gram-positive bacteria, including MRSA isolates resistant to linezolid.
      Pivotal clinical trials showed that tedizolid at 200 mg once-daily for 6 days is
      not inferior to linezolid 600 mg twice daily for 10 days in patients with SSTI.
      The comparison of adverse events is favorable to tedizolid under the
      circumstances of the clinical trials. This is a review of recent literature on
      tedizolid, its use in special populations and potential adverse effects. RECENT
      FINDINGS: Findings suggest that tedizolid can be used in SSTI in adolescents,
      those older than 65 years, obese individuals and patients with diabetic foot
      infections. Forthcoming research to determine the future uses of this drug in
      other clinical syndromes requires demonstration of tolerance whenever tedizolid
      is administered for longer than 6 days.We also speculate on missing data and
      potential future indications of tedizolid in the highly competitive field of the
      treatment of severe Gram-positive infections other than SSTI. SUMMARY: Tedizolid
      is a second-generation oxazolidinone, very convenient for treatment of SSTI, in
      search for other indications including nosocomial pneumonia and bone and joint
      infections. VIDEO ABSTRACT.

PMID- 29346120
TI  - A View From the UK: The UK and Ireland Confidential Enquiry into Maternal Deaths
      and Morbidity.
AB  - The UK Confidential Enquiry into Maternal Deaths has been in operation for more
      than 60 years, during which time maternal mortality rates have fallen 10-fold.
      The program includes two aspects, surveillance and confidential case review,
      providing different information to aid quality improvement in maternity care. The
      enquiry now also reviews the care of women with specific severe morbidities.
      Recommendations have very clearly led to improved outcomes for women, most
      notably shown in the very low mortality rate due to hypertensive and related
      disorders of pregnancy. Maternal cardiac disease and mental health problems
      remain the major areas still to be addressed.

PMID- 29346122
TI  - Bolus Norepinephrine Administration and Fetal Acidosis at Cesarean Delivery Under
      Spinal Anesthesia.

PMID- 29346123
TI  - In Response.

PMID- 29346121
TI  - Reducing Disparities in Severe Maternal Morbidity and Mortality.
AB  - Significant racial and ethnic disparities in maternal morbidity and mortality
      exist in the United States. Black women are 3 to 4 times more likely to die a
      pregnancy-related death as compared with white women. Growing research indicates
      that quality of health care, from preconception through postpartum care, may be a
      critical lever for improving outcomes for racial and ethnic minority women. This
      article reviews racial and ethnic disparities in severe maternal morbidities and
      mortality, underlying drivers of these disparities, and potential levers to
      reduce their occurrence.

PMID- 29346124
TI  - In Response.

PMID- 29346125
TI  - The Unknown Mechanism of Exogenous Tetrahydrobiopterin in the Renal Protection of
      Sheep Ischemia and Reperfusion.

PMID- 29346126
TI  - Complete revascularization for patients with ST-segment elevation myocardial
      infarction and multivessel coronary artery disease: a meta-analysis of randomized
      trials.
AB  - INTRODUCTION: Despite the recent findings in randomized clinical trials (RCTs)
      with limited sample sizes and the updates in clinical guidelines, the current
      available data for the complete revascularization (CR) in hemodynamically stable
      patients with ST-segment elevation myocardial infarction (STEMI) at the time of
      primary percutaneous coronary intervention (PCI) are still contradictory. AIM:
      The aim of this meta-analysis of the existing RCTs was to assess the efficacy of
      the CR versus revascularization of infarct-related artery (IRA) only during
      primary PCI in patients with STEMI and multivessel disease (MVD). PATIENTS AND
      METHODS: We searched PubMed, MEDLINE, Embase, Scopus, Google Scholar, Cochrane
      Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov databases
      aiming to find RCTs for patients with STEMI and MVD which compared CR with IRA
      only. Random effect risk ratios (RRs) were calculated for efficacy and safety
      outcomes. RESULTS: Ten RCTs with 3291 patients were included. The median follow
      up duration was 17.5 months. Major adverse cardiac events (RR=0.57; 0.43-0.76;
      P<0.0001), cardiac mortality (RR=0.52; 0.31-0.87; P=0.014), and repeat
      revascularization (RR=0.50; 0.30-0.84; P=0.009) were lower in CR compared with
      IRA-only strategies. However, there was no significant difference in the risk of
      all-cause mortality, recurrent nonfatal myocardial infarction, stroke, major
      bleeding events, and contrast-induced nephropathy. CONCLUSION: For patients with
      STEMI and MVD undergoing primary PCI, the current evidence suggests that the risk
      of major adverse cardiac events, repeat revascularization, and cardiac death is
      reduced by CR. However, the risk for all-cause mortality and PCI-related
      complications is not different from the isolated culprit lesion-only treatment.
      Although these findings support the cardiac mortality and safety benefit of CR in
      stable STEMI, further large trials are required to provide better guidance for
      optimum management of such patients.

PMID- 29346127
TI  - Rivaroxaban with or without aspirin for prevention of cardiovascular disease.

PMID- 29346128
TI  - Management of heavy menstrual bleeding during direct oral anticoagulant therapy
      for recurrent venous thromboembolism: a case report.
AB  - : A high risk of venous thromboembolism (VTE) recurrence requires extended
      anticoagulation but limits the options to control heavy menstrual bleeding (HMB)
      in women of reproductive age. We report the management of HMB in a 48-year-old
      woman with a history of menometrorrhagia, recurrent VTE and multiple VTE risk
      factors. Due to the occurrence of HMB during extended rivaroxaban treatment, the
      presence of a uterine fibroid and the contraindication to interrupt
      anticoagulation for high risk of VTE recurrence, she received hormonal treatment
      first with a gonadotropin-releasing hormone agonist and then with progestin. This
      strategy allowed to adequately control HMB, without rivaroxaban discontinuation
      or dose reduction, and no new thromboembolic and no more bleeding events occurred
      over a long follow-up period of more than 20 months. In conclusion, the use of
      hormonal therapy in VTE women requiring long-term anticoagulation may be an
      option to control HMB, without further increasing the risk of VTE recurrence.

PMID- 29346129
TI  - High Inflammatory Infiltrate Correlates With Poor Symptomatic Improvement After
      Surgical Treatment for Superior Limbic Keratoconjunctivitis.
AB  - PURPOSE: Superior limbic keratoconjunctivitis (SLK) is a chronic and recurrent
      condition of unknown etiology. It is often managed conservatively, but there is a
      high rate of success with surgical management for severe or recalcitrant cases.
      The purpose of this article is to describe and analyze clinicopathological
      features of patients with SLK who underwent surgical treatment and their
      association with the clinical outcome. METHODS: A total of 22 eyes from 18
      patients who underwent surgical SLK management were retrospectively analyzed.
      Clinicopathological data were collected including details of follow-up and
      patient satisfaction (n = 15). Moreover, 12 cases had specimens available for
      review of histopathologic findings and COX-2 expression analysis by
      immunohistochemistry. RESULTS: From a clinical perspective, 66.7% of the SLK eyes
      had nonmechanical factors contributing to SLK, and 66.7% of eyes demonstrated
      significant symptomatic improvement after surgery. Histopathological analysis of
      all the lesions showed acanthosis and goblet cell loss. Unexpectedly, in 93% of
      the eyes, dilated lymphatic vessels were found. Furthermore, a high inflammatory
      infiltrate correlated with minimal symptomatic improvements (P = 0.013).
      Moreover, COX-2 expression was higher in patients with SLK than in a normal
      conjunctiva (P = 0.001). CONCLUSIONS: In this study, the most common systemic
      association with SLK was the patient's autoimmune status. Histopathological
      evaluation revealed that high inflammatory infiltration in the biopsy might be
      predictive of minimal symptomatic improvement with surgical management. Finally,
      the higher COX-2 expression in patients with SLK compared with that in
      individuals with a normal conjunctiva supports the use of anti-COX-2 drugs as a
      possible therapeutic target.

PMID- 29346130
TI  - Reply: Management of Descemet Membrane Detachment After Forceps Birth Injury.

PMID- 29346131
TI  - Toxicological profile and safety pharmacology of a single dose of fibroblast
      activation protein-alpha-based doxorubicin prodrug: in-vitro and in-vivo
      evaluation.
AB  - Fibroblast activation protein-alpha (FAPalpha) is a promising tumor-associated
      target expressed by reactive stromal fibroblasts in tumor tissue. FAPalpha has a
      postprolyl peptidase activity and can specifically cleave N-terminal
      benzyloxycarbonyl (Z)-blocked peptides, such as the substrate Z-Gly-Pro-AMC.
      Doxorubicin (DOX) is an effective antitumor drug, but its application is greatly
      limited by toxic adverse effects owing to poor tumor selectivity. Based on these
      facts, we previously designed a FAPalpha-targeting prodrug of doxorubicin (FTPD)
      which can be selectively hydrolyzed by FAPalpha. FTPD can retain potent antitumor
      efficacy and has favorable tumor targeting. The present study aimed to further
      evaluate the toxicological profile and the safety pharmacological property of
      FTPD in vitro and in vivo. The cytotoxicity assay showed that FTPD displayed
      markedly lower cytotoxicity to 3T3 cells and HEK-293 cells compared with DOX. In
      the short-term toxicity study, mice treated with 25 mg/kg of FTPD showed no
      obvious change in the appearance and general behavior, and no case of mortality
      was observed within 14 days. Unlike DOX, FTPD exhibited reduced toxicity to
      heart, liver, kidney, spleen as well as peripheral white blood cells in mice.
      Moreover, open file test and general pharmacology study were also conducted
      correspondingly in mice and beagle dogs. It was found that FTPD may not produce
      significant pharmacological effects on spontaneous locomotor activity and
      cardiovascular-respiratory system except for a transient decreasing in systolic
      blood pressure. Taken together, the results of this work suggest that FTPD has
      more favorable toxicological profile and better drug safety compared with its
      parent drug DOX.

PMID- 29346132
TI  - Enzymatic sources and physio-pathological functions of soluble (pro)renin
      receptor.
AB  - PURPOSE OF REVIEW: (Pro)renin receptor (PRR) belongs to type I transmembrane
      receptor family and binds both prorenin and renin, representing a potential
      regulator of the activity of the renin-angiotensin system. Soluble form of PRR
      (sPRR) is generated by intracellular protease-mediated cleavage of full-length
      PRR. The purpose of this review is to highlight recent advances in understanding
      the mechanisms of action and production of sPRR. RECENT FINDINGS: It has recently
      been demonstrated that site-1-protease (S1P) plays a dominant role in the
      generation of sPRR. New evidence is also emerging to support a biological
      function of sPRR in the physiological regulation of fluid homeostasis as well as
      pathogenesis of chronic kidney disease. SUMMARY: sPRR is a 28 kDa product of PRR
      cleavage via S1P-mediated protease activity. Not only does sPRR regulate renal
      tubular water transport, but it also mediates pathogenic responses to renal
      cellular injury. sPRR is likely involved in a wide range of physio-pathological
      processes.

PMID- 29346133
TI  - Dexmedetomidine Impairs Diaphragm Function and Increases Oxidative Stress but
      Does Not Aggravate Diaphragmatic Atrophy in Mechanically Ventilated Rats.
AB  - BACKGROUND: Anesthetics in ventilated patients are critical as any cofactor
      hampering diaphragmatic function may have a negative impact on the weaning
      progress and therefore on patients' mortality. Dexmedetomidine may display
      antioxidant and antiproteolytic properties, but it also reduced glucose uptake by
      the muscle, which may impair diaphragm force production. This study tested the
      hypothesis that dexmedetomidine could inhibit ventilator-induced diaphragmatic
      dysfunction. METHODS: Twenty-four rats were separated into three groups (n =
      8/group). Two groups were mechanically ventilated during either dexmedetomidine
      or pentobarbital exposure for 24 h, referred to as interventional groups. A third
      group of directly euthanized rats served as control. Force generation, fiber
      dimensions, proteolysis markers, protein oxidation and lipid peroxidation,
      calcium homeostasis markers, and glucose transporter-4 (Glut-4) translocation
      were measured in the diaphragm. RESULTS: Diaphragm force, corrected for cross
      sectional area, was significantly decreased in both interventional groups
      compared to controls and was significantly lower with dexmedetomidine compared to
      pentobarbital (e.g., 100 Hz: -18%, P < 0.0001). In contrast to pentobarbital,
      dexmedetomidine did not lead to diaphragmatic atrophy, but it induced more
      protein oxidation (200% vs. 73% in pentobarbital, P = 0.0015), induced less
      upregulation of muscle atrophy F-box (149% vs. 374% in pentobarbital, P < 0.001)
      and impaired Glut-4 translocation (-73%, P < 0.0005). It activated autophagy, the
      calcium-dependent proteases, and caused lipid peroxidation similarly to
      pentobarbital. CONCLUSIONS: Twenty-four hours of mechanical ventilation during
      dexmedetomidine sedation led to a worsening of ventilation-induced diaphragm
      dysfunction, possibly through impaired Glut-4 translocation. Although
      dexmedetomidine prevented diaphragmatic fiber atrophy, it did not inhibit
      oxidative stress and activation of the proteolytic pathways.

PMID- 29346134
TI  - Effect of Maternal Body Mass Index on Postpartum Hemorrhage.
AB  - BACKGROUND: It is unclear whether obesity is a risk factor for postpartum
      hemorrhage. The authors hypothesized that obese women are at greater risk of
      hemorrhage than women with a normal body mass index. METHODS: The authors
      conducted a cohort study of women who underwent delivery hospitalization in
      California between 2008 and 2012. Using multilevel regression, the authors
      examined the relationships between body mass index with hemorrhage (primary
      outcome), atonic hemorrhage, and severe hemorrhage (secondary outcomes).
      Stratified analyses were performed according to delivery mode. RESULTS: The
      absolute event rate for hemorrhage was 60,604/2,176,673 (2.8%). In this cohort,
      4% of women were underweight, 49.1% of women were normal body mass index, 25.9%
      of women were overweight, and 12.7%, 5.2%, and 3.1% of women were in obesity
      class I, II, and III, respectively. Compared to normal body mass index women, the
      odds of hemorrhage and atonic hemorrhage were modestly increased for overweight
      women (hemorrhage: adjusted odds ratio [aOR], 1.06; 99% CI, 1.04 to 1.08; atonic
      hemorrhage: aOR, 1.07; 99% CI, 1.05 to 1.09) and obesity class I (hemorrhage:
      aOR, 1.08; 99% CI, 1.05 to 1.11; atonic hemorrhage; aOR, 1.11; 99% CI, 1.08 to
      1.15). After vaginal delivery, overweight and obese women had up to 19% increased
      odds of hemorrhage or atonic hemorrhage; whereas, after cesarean delivery, women
      in any obesity class had up to 14% decreased odds of severe hemorrhage.
      CONCLUSIONS: The authors' findings suggest that, at most, maternal obesity has a
      modest effect on hemorrhage risk. The direction of the association between
      hemorrhage and body mass index may differ by delivery mode.

PMID- 29346135
TI  - Behavioral Health Training in Pediatric Residency Programs: A National Survey of
      Training Directors.
AB  - OBJECTIVE: To identify perceptions of behavioral health (BH) training in
      pediatric residency programs, the degree of involvement from behavioral health
      providers (BHPs), and opportunities for and barriers to innovation in training.
      METHOD: A tailored design methodology was used to target all pediatric residency
      program directors in the United States (N = 214). Participants were identified
      from the Electronic Residency Application Service website of the Association of
      American Medical Colleges and were asked to complete a 22-item item survey on BH
      training. RESULTS: A 69.2% usable response rate (N = 148) was obtained. A total
      of 62.8% of directors described training in the developmental-behavioral
      pediatrics (DBP) rotation as optimal; 36% described BH training in the residency
      program as a whole (i.e., outside the DBP rotation) as optimal. Only 20.3%
      described "common factors" training as optimal, and the quality of training in
      this area was positively and significantly related to the quality of BH training
      in the residency program as a whole (chi = 35.05, p < 0.001). The quality of
      common factors training was significantly higher in programs that had embedded
      BHPs (i.e., psychologists and social workers) in the continuity clinic than
      programs that did not (chi = 7.65, p = 0.04). Barriers to quality training
      included instructional content, instructional methods, stakeholder support, and
      resources. CONCLUSION: Despite substantial improvement in residency training in
      BH over the last decade, additional improvement is needed. Barriers to continued
      improvement include training content, training methods, support from faculty and
      administrator stakeholders, and resource issues. Strategies derived from
      implementation science have the potential to address these barriers.

PMID- 29346136
TI  - Interdisciplinary Team Evaluation: An Effective Method for the Diagnostic
      Assessment of Autism Spectrum Disorder.
AB  - OBJECTIVE: The objective of this research is to assess the feasibility of an
      interdisciplinary team diagnostic assessment model for autism spectrum disorder
      (ASD). METHOD: Medical records from 366 patients evaluated for ASD at the Seattle
      Children's Autism Center (SCAC) were reviewed. ASD diagnostic outcomes, provider
      satisfaction, engagement in follow-up care, billed time, and reimbursement
      amounts were compared in patients evaluated through an interdisciplinary team
      approach (n = 91) with those seen in multidisciplinary evaluations led by either
      a psychologist (n = 165) or a physician (n = 110). RESULTS: Diagnostic
      determination was made in 90% of patients evaluated through the interdisciplinary
      team model in a single day. Rates of ASD diagnosis were similar across the 3
      tracks, ranging from 61% to 72%. Demographic characteristics did not impact the
      likelihood of ASD diagnosis. Rates of patient follow-up care and provider
      satisfaction were significantly higher in interdisciplinary versus
      multidisciplinary teams. Interdisciplinary team evaluations billed 1.8 fewer
      hours yet generated more net hourly clinic income compared with psychology-led
      multidisciplinary evaluations. CONCLUSION: An interdisciplinary team approach,
      focusing on ruling-in or ruling-out ASD, was sufficient to determine ASD
      diagnosis in most patients seen at the SCAC Interdisciplinary teams generated
      more clinic income and decreased the time spent in evaluation compared with a
      psychology-led approach. They did so while maintaining consistency in diagnostic
      rates, demonstrating increased provider satisfaction and an increased likelihood
      of engagement in follow-up care.

PMID- 29346137
TI  - Guidance Provided to Authors on Citing and Formatting References in Nursing
      Journals.
AB  - Reference citations should be accurate, complete, and presented in a consistent
      format. This study analyzed information provided to authors on preparing
      citations and references for manuscripts submitted to nursing journals (n = 209).
      Half of the journals used the American Psychological Association reference style.
      Slightly more than half provided examples of how to cite articles and books;
      there were fewer examples of citing websites and online journals. Suggestions on
      improving accuracy of references are discussed.

PMID- 29346138
TI  - Obesity and chronic kidney disease.
AB  - PURPOSE OF REVIEW: To review recent advances in the epidemiology,
      pathophysiology, clinical features, and treatment of obesity-related kidney
      disease. RECENT FINDINGS: Studies have confirmed that obesity is associated with
      increased risk of developing chronic kidney disease (CKD). This risk extends to
      those who are metabolically healthy, indicating that obesity per se contributes
      to CKD independent of the metabolic syndrome. Recent developments in the
      pathophysiology of obesity-related kidney disease indicate that chronic
      inflammation and abnormal lipid metabolism contribute to kidney cell injury.
      Children with severe obesity have increased prevalence of early kidney
      abnormalities, including albuminuria, decreased kidney function, and elevated
      biomarkers of early kidney injury. For these patients, bariatric surgery has
      emerged as a treatment option to consider. Longitudinal studies in children and
      adults have demonstrated that in patients with obesity-related kidney disease,
      kidney function and albuminuria improve following bariatric surgery. SUMMARY: The
      injurious renal effects of obesity are present in childhood, although the natural
      history and clinical spectrum of obesity-related kidney disease in children are
      not known. In obese children with early kidney disease, identification of kidney
      injury, implementation of preventive strategies, and prompt treatment are
      essential to improving clinical outcomes.

PMID- 29346139
TI  - Blood biomarkers for evaluation of perinatal encephalopathy: state of the art.
AB  - PURPOSE OF REVIEW: The rapid progress in biomarker science is on the threshold of
      significantly changing clinical care for infants in the neonatal ICU. Infants
      with neonatal brain injuries will likely be the first group whose management is
      dramatically altered with point-of-care, rapidly available brain biomarker
      analysis. Providing an interim update on progress in this area is the purpose of
      this review. RECENT FINDINGS: Highlighted findings from the past 18 months of
      publications on biomarkers in neonatal brain injury include; Specific nonbrain
      markers of cardiac health and global asphyxia continue to provide information on
      brain injury after hypoxic-ischemic encephalopathy (HIE). Prediction of injury in
      the piglet hypoxia-ischemia model is improved with the use of a combination score
      of plasma metabolites. In a neonatal piglet model of perinatal hypoxia-ischemia,
      a systemic proinflammatory surge of cytokines has been identified after rewarming
      from therapeutic hypothermia. New biomarkers identified recently include
      osteopontin, activin A, neutrophil gelatinase-associated lipocalin,
      secretoneurin, Tau and neurofilament light protein. Brain-based biomarkers differ
      in their ability to predict short-term in-hospital outcomes and long-term
      neurologic deficits. SUMMARY: Neonatal brain biomarker research is currently in
      its very early development with major advances still to be made.

PMID- 29346140
TI  - Neonatal hypoglycemia: continuous glucose monitoring.
AB  - PURPOSE OF REVIEW: Continuous glucose monitoring (CGM) is increasingly used in
      the management of diabetes in children and adults, but there are few data
      regarding its use in neonates. The purpose of this article is to discuss the
      potential benefits and limitations of CGM in neonates. RECENT FINDINGS: Smaller
      electrodes in new sensors and real-time monitoring have made CGM devices more
      approachable for neonatal care. CGM is well tolerated in infants including very
      low birth weight babies, and few if any local complications have been reported.
      Use of CGM in newborns may reduce the frequency of blood sampling and improve
      glycemic stability, with more time spent in the euglycemic range. However, CGM
      may also lead to more intervention, with potential adverse effects on outcomes.
      More information is also needed about reliability, calibration and interpretation
      of CGM in the neonate. SUMMARY: Although the use of CGM in neonates appears to be
      well tolerated, feasible and has been associated with better glycemic status,
      there is not yet any evidence of improved clinical outcomes. Clinical utility of
      CGM should be demonstrated in randomized trials prior to its introduction into
      regular neonatal care.

PMID- 29346141
TI  - Caffeine controversies.
AB  - PURPOSE OF REVIEW: Caffeine use in preterm infants has endured several paradigms:
      from standard of care to possible neurotoxin to one of the few medications for
      which there is evidence of bronchopulmonary dysplasia (BPD) risk reduction. The
      purpose of the review is to analyze this dynamic trajectory and discuss
      controversies that still remain after decades of caffeine use. RECENT FINDINGS:
      Following concerns for caffeine safety in preterm infants, a large randomized
      controlled trial demonstrated a reduction in BPD and treatment for patent ductus
      arteriosus. The lower rate of death or neurodevelopmental impairment noted at 18
      21 months was not statistically different at later timepoints; however, infants
      in the caffeine group had lower rates of motor impairment at 11-year follow-up.
      The time of caffeine therapy initiation is now substantially earlier, and doses
      used are sometimes higher that previously used, but there are limited data to
      support these practices. SUMMARY: Caffeine therapy for apnea of prematurity (AOP)
      remains one of the pillars of neonatal care, although more evidence to support
      dosing and timing of initiation and discontinuation are needed.

PMID- 29346142
TI  - Neonatal abstinence syndrome: an update.
AB  - PURPOSE OF REVIEW: The current review provides an update focused on the evolving
      epidemiology of neonatal abstinence syndrome (NAS), factors influencing disease
      expression, advances in clinical assessment of withdrawal, novel approaches to
      NAS treatment, and the emerging role of quality improvement in assessment and
      management of NAS. RECENT FINDINGS: The rise in the incidence of NAS
      disproportionately occurred in rural and suburban areas. Polysubstance exposure
      and genetic polymorphisms have been shown to modify NAS expression and severity.
      New bedside assessments using a limited number of factors to identify infants
      with NAS result in fewer infants receiving pharmacotherapy. In addition,
      buprenorphine may be a promising therapeutic alternative to morphine to treat
      NAS. Lastly, local, state, and national quality improvement initiatives have
      emerged as an effective mechanism to advance the care of infants with NAS.
      SUMMARY: NAS remains a critical public health issue associated with significant
      medical, economic, and personal burdens. Emerging data on associated risk
      factors, assessment of and treatment for NAS provide clinicians and hospitals
      with new knowledge and an urgency to promote standardization of care for infants
      with NAS.

PMID- 29346143
TI  - Progression of chronic kidney disease in children.

PMID- 29346144
TI  - Making Keys, Looking for Locks: Technology-Driven Versus Patient-Focused Medical
      Devices.

PMID- 29346145
TI  - Diagnostic and Therapeutic Ultrasound on Venous and Arterial Ulcers: A Focused
      Review.
AB  - GENERAL PURPOSE: To provide information about the use of ultrasound for
      diagnostic and therapeutic treatment of venous and arterial ulcers. TARGET
      AUDIENCE: This continuing education activity is intended for physicians,
      physician assistants, nurse practitioners, and nurses with an interest in skin
      and wound care. LEARNING OBJECTIVES/OUTCOMES: After completing this continuing
      education activity, you should be able to: ABSTRACT: To review the diagnostic and
      therapeutic use of ultrasound on venous and arterial ulcers. METHODS: PubMed was
      searched for peer-reviewed articles using the search terms "ultrasound for venous
      ulcers" and "ultrasound for arterial ulcers." The search yielded 282 articles on
      ultrasound for venous ulcers and 455 articles for ultrasound on arterial ulcers.
      Data from 36 articles were selected and included after abstract review. RESULTS:
      Ultrasound is an established diagnostic modality for venous and arterial disease
      and is indicated for wound debridement. Recent evidence continues to support its
      superiority over standard of care in healing venous ulcers, but findings conflict
      in terms of the effectiveness of low-frequency ultrasound over high-frequency
      ultrasound. There are currently no standardized treatment protocols for
      ultrasound. CONCLUSIONS: Diagnostic ultrasound is used to assess venous and
      arterial disease and guide appropriate treatment for ulcers. Therapeutic low
      frequency ultrasound is used to debride the wound bed, as an adjunctive topical
      wound treatment with standard of care, and to guide the application of other
      advanced therapies to chronic wounds. Better trial designs and consistent data
      are needed to support the effectiveness of ultrasound therapy on venous and
      arterial ulcers.

PMID- 29346146
TI  - Use of Oxidized Regenerated Cellulose/Collagen Matrix in Chronic Diabetic Foot
      Ulcers: A Systematic Review.
AB  - OBJECTIVE: Diabetic wounds that do not heal completely usually exhibit
      inflammatory markers, increased protease activity, and reduced levels of growth
      factors and cell count. A systematic review was performed to determine whether
      there is enough evidence to support the use of an oxidized regenerated
      cellulose/collagen matrix (ORC+C) to treat diabetic foot ulcers (DFUs). METHODS:
      Study authors analyzed randomized controlled trials (RCTs) on ORC+C dressings for
      the treatment of DFUs. A literature search was conducted for all available
      reports of relevant studies published in journals indexed in PubMed, LILACS, and
      SciELO databases. There were no restrictions based on date of publication. A
      population-intervention-comparison-outcome framework was built on MeSH terms and
      keywords. Two independent researchers analyzed all articles for data collection
      and used the Cochrane Collaboration tool for risk-of-bias assessment. RESULTS: At
      first, 316 related studies were located in the databases. After evaluating these
      studies for methodological similarities, only 3 were considered eligible for the
      review. One RCT was considered at high risk of bias. Results from this meta
      analysis of 2 studies showed no significant improvement in wound healing rates of
      DFUs when ORC+C was compared with standard wound care. CONCLUSIONS: Because of
      several methodology flaws in the reviewed studies, these results suggest that
      there is currently no research evidence to suggest that the use of ORC+C improves
      wound healing rates of DFUs. Additional research with high-quality RCTs focused
      on diabetic ulcers is necessary.

PMID- 29346147
TI  - Hypoperfusion and Wound Healing: Another Dimension of Wound Assessment.
AB  - OBJECTIVE: To examine the correlation between mean arterial pressure (MAP) and
      wound healing indices and describe an analytical process that can be used
      accurately and prospectively when evaluating all types of skin ulcerations.
      METHODS: A correlational study in a long-term-care facility.Participants (N =
      230) were adults residing in a long-term-care facility with an average age of
      77.8 years (range, 35-105). MAIN OUTCOME MEASURES: Assessment through both an
      index of wound healing and wound surface area. Signs of wound healing included a
      reduction of surface area and surface necrosis and increased granulation or
      epithelialization. RESULTS: Aggregate analyses for all wound locations revealed a
      positive correlation between the MAP and index of wound healing (r = 0.86, n =
      501, P < .0001). A well-defined positive correlation between the MAP and stalled
      or poor wound healing was noted for all wound locations in this data set when MAP
      values were 80 mm Hg or less (r = 0.95, n = 141, P < .0001). Further, the data
      set of truncal wounds and MAP of less than 80 mm Hg yielded a very strong
      positive correlation. The data indicated that as perfusion decreased, wounds
      within the sample population declined (r = 0.93, n = 102, P < .0001). CONCLUSION:
      The data suggest that MAP values less than 80 mm Hg can independently result in
      stalled wound healing or worsened wounds. A predictability of wounds stalling or
      declining related to the MAP was observed, regardless of topical treatment or
      standard-of-care interventions. Therefore, the data also suggest that remediating
      states of low perfusion should take precedence in making treatment decisions.

PMID- 29346148
TI  - Vertical Profunda Artery Perforator Flap for Plantar Foot Wound Closure: A New
      Application.
AB  - BACKGROUND: Plantar foot reconstruction requires special consideration of both
      form and function. There are several fasciocutaneous flap options, each with
      indications and reservations. CASE STUDY: This case presents a new application of
      the vertical profunda artery perforator flap for definitive closure of a
      neuropathic foot ulcer in a young woman with spina bifida. The postoperative
      course was uneventful, and the flap survived completely. The surgical and donor
      sites were without wound recurrence at 5-month follow-up. DISCUSSION:
      Understanding the variability of foot flap options is important because of unique
      cases such as the one presented where the wound was caused by specific and less
      commonly observed foot anatomy. The specific choice to use the vertical profunda
      artery perforator flap for this patient and her neuropathic wound type was made
      based on its excellent flexibility, durability, and donor site appeal.
      CONCLUSIONS: The vertical profunda artery perforator flap has adequate surface
      area and bulk and a favorable pedicle length and caliber, can be thinned, and
      leaves a donor scar in a less conspicuous area than other popular free flaps for
      lower-extremity reconstruction. For these reasons, it should be considered a
      first-line therapy for free flap coverage of selected foot wounds.

PMID- 29346149
TI  - Testing Elevated Protease Activity: Prospective Analysis of 160 Wounds.
AB  - OBJECTIVE: Given that local elevated protease activity (EPA) has been implicated
      in impaired wound healing, a prospective single-center study was conducted to
      assess protease activity in various wound types. METHODS: Protease activity was
      determined using an easy-to-use test system (Woundchek Protease Status Test Kit;
      Systagenix, Gatwick, United Kingdom) in 160 wounds in 143 patients. The assay
      detects the combined activity of inflammatory proteases, mainly matrix
      metalloproteinases 8 and 9 and human neutrophil elastase. RESULTS: Local EPA was
      detected in 29 of 153 validly tested wounds (18.95%). No difference was detected
      between acute and chronic wounds, regardless of associated or causative
      conditions, with the sole exception of surgical wounds. Surgical wounds showed
      EPA significantly less frequently than nonsurgical wounds. Among nonsurgical
      wounds, EPA was detected more frequently in acute compared with chronic wounds.
      Wounds with signs of unimpeded healing (granulation or epithelialization) showed
      EPA less often than wounds covered with necrotic tissue or a fibrin layer.
      However, 14% of wounds with epithelialization or granulation exhibited EPA
      potentially impeding wound healing. Wounds treated with moisture-retentive wound
      dressings showed EPA significantly less frequently compared with wounds bandaged
      with dressings with less moisture-retentive properties. Remarkably, none of the
      wounds treated with collagen/oxidized regenerated cellulose/silver, which is a
      protease-modulating dressing, showed EPA. CONCLUSIONS: To the study authors'
      knowledge, this is the largest study assessing EPA in various wound types. The
      convenient applicability of the test system provides a basis for future studies
      assessing the pathophysiologic relevance of EPA. In some unsuspicious wounds,
      early detection of EPA might precede impaired healing and prompt protease
      modulating treatment before failure to heal becomes apparent.

PMID- 29346150
TI  - Orders and Documentation Are Vital to Diabetic Shoe Coverage.

PMID- 29346154
TI  - The Cornerstone of Compliance: Your Workflow.

PMID- 29346155
TI  - Diagnostic and Therapeutic Ultrasound on Venous and Arterial Ulcers: A Focused
      Review.

PMID- 29346156
TI  - Developing a Mobile App for Prevention and Treatment of Pressure Injuries.
AB  - OBJECTIVE: This descriptive study describes the planning and development of a
      mobile application (app) for prevention and treatment of pressure injuries for
      use by providers in a university research center. The app delineates risk factors
      for pressure injury development, provides an evaluation of the wound, recommends
      wound cleansing procedures, performs pressure injury staging, and recommends
      treatment interventions. METHODS: A mobile app was developed using a
      contextualized instructional design, which involves a constructivist proposal and
      planning, developing, and applying specific didactic situations, thus
      incorporating mechanisms that favor contextualization. A literature search was
      conducted to identify relevant studies for the construction of the mobile app.
      The development process involved the selection of app tools, definition of the
      navigation structure, and planning of the environment configuration. The
      environment for downloading the app software on the Internet and installing it on
      the mobile device was created. MAIN RESULTS: The literature search yielded 18
      articles, 2 books, and 1 master's degree thesis. A mobile app was created with an
      easy-to-use graphic interface. The app stores the patient's demographic
      characteristics and provides an evaluation of his/her wound, a list of risk
      factors for pressure injury development, wound cleansing procedures, and
      treatment interventions. CONCLUSIONS: The developed app may be useful in clinical
      practice, helping to prevent pressure injuries and promote select nursing
      interventions for the treatment of patients with pressure injury.

PMID- 29346158
TI  - Biomechanical Response to Osteoarthritis Pain Treatment May Impair Long-Term
      Efficacy.
AB  - Pain has an important physiologic role and acts with or stimulates motor system
      adaptations to protect tissue from threats of damage. Although clinically
      beneficial, removing the protective pain response may have negative consequence
      in osteoarthritis, a mechanically mediated disease. We hypothesize motor system
      adaptations to joint pain and its treatment may impact osteoarthritis
      progression, thereby limiting efficacy of pain therapies.

PMID- 29346157
TI  - Identifying Novel Signaling Pathways: An Exercise Scientists Guide to
      Phosphoproteomics.
AB  - We propose that phosphoproteomic-based studies will radically advance our
      knowledge about exercise-regulated signaling events. However, these studies use
      cutting-edge technologies that can be difficult for nonspecialists to understand.
      Hence, this review is intended to help nonspecialists 1) understand the
      fundamental technologies behind phosphoproteomic analysis and 2) use various
      bioinformatic tools that can be used to interrogate phosphoproteomic datasets.

PMID- 29346159
TI  - Making a Case for Cardiorespiratory Fitness Surveillance Among Children and
      Youth.
AB  - We review the evidence that supports cardiorespiratory fitness (CRF) as an
      important indicator of current and future health among school-aged children and
      youth, independent of physical activity levels. We discuss the merit of CRF
      measurement for population health surveillance and propose the development of CRF
      guidelines to help support regional, national, and international surveillance
      efforts.

PMID- 29346160
TI  - Potential Role of MicroRNA in the Anabolic Capacity of Skeletal Muscle With
      Aging.
AB  - Age-induced loss of skeletal muscle mass and function, termed sarcopenia, may be
      the result of diminished response to anabolic stimulation. This review will
      explore the hypothesis that alterations in the expression of microRNA with aging
      contributes to reduced muscle plasticity resulting in impaired skeletal muscle
      adaptations to exercise-induced anabolic stimulation.

PMID- 29346161
TI  - Promotion of Exercise in Multiple Sclerosis Through Health Care Providers.
AB  - Participation in exercise yields meaningful benefits among persons with multiple
      sclerosis (MS), yet this population engages in low rates of health-promoting
      physical activity. The disconnect between evidence of benefits and rates of
      participation requires consideration of new opportunities for changing this
      health behavior. The current article hypothesizes that the patient-provider
      interaction offers a fertile opportunity for promoting exercise behavior in MS.

PMID- 29346162
TI  - Specificity of "Live High-Train Low" Altitude Training on Exercise Performance.
AB  - The novel hypothesis that "Live High-Train Low" (LHTL) does not improve sport
      specific exercise performance (e.g., time trial) is discussed. Indeed, many
      studies demonstrate improved performance after LHTL but, unfortunately, control
      groups are often lacking, leaving open the possibility of training camp effects.
      Importantly, when control groups, blinding procedures, and strict scientific
      evaluation criteria are applied, LHTL has no detectable effect on performance.

PMID- 29346163
TI  - The Hippo Signaling Pathway in the Regulation of Skeletal Muscle Mass and
      Function.
AB  - The Hippo signaling pathway regulates the activity of the proteins Yes-associated
      protein (Yap) and transcriptional co-activator with PDZ-binding motif (Taz) to
      control tissue growth in many different cell types. Previously, we demonstrated
      that Yap is a critical regulator of skeletal muscle mass. We hypothesize that
      alterations in Yap and Taz activity modulate the anabolic adaptations of skeletal
      muscle to resistance exercise.

PMID- 29346164
TI  - The Nuclear Receptor Nor-1 Is a Pleiotropic Regulator of Exercise-Induced
      Adaptations.
AB  - Exercise induces various physical and metabolic changes in skeletal muscle that
      adaptively reprograms this tissue to current physiological and environmental
      demands. Underlying these changes are broad modifications to gene expression. We
      postulate that the nuclear hormone receptor, Nor-1, is activated after exercise,
      and this transcription factor modifies gene expression to drive the molecular and
      cellular adaptations associated with contractile reorganization.

PMID- 29346165
TI  - Using Drosophila to Understand Biochemical and Behavioral Responses to Exercise.
AB  - The development of endurance exercise paradigms in Drosophila has facilitated
      study of genetic factors that control individual response to exercise. Recent
      work in Drosophila has demonstrated that activation of octopaminergic neurons is
      alone sufficient to confer exercise adaptations to sedentary flies. These results
      suggest that adrenergic activity is both necessary and sufficient to promote
      endurance exercise adaptations.

PMID- 29346166
TI  - Cardiorespiratory Fitness in Children and Youth: A Call for Surveillance, But Now
      How Do We Do It?

PMID- 29346167
TI  - New Reference Values for Cardiopulmonary Exercise Testing in Children.
AB  - INTRODUCTION: Cardiopulmonary exercise testing is an essential tool to assess
      cardiorespiratory fitness (CRF) in children. There is a paucity of adequate
      pediatric reference values that are independent of body size and pubertal stage.
      The purpose of this study is to provide Z score equations for several maximal and
      submaximal CRF parameters derived from a prospectively recruited sample of
      healthy children. METHODS: In this cross-sectional multicenter study, we
      prospectively recruited 228 healthy children 12 to 17 yr old in local schools. We
      performed a symptom-limited cardiopulmonary exercise testing progressive ramp
      protocol on an electronically braked cycle ergometer. Eighteen CRF parameters
      were analyzed. We tested several regression models to obtain prediction curves
      that minimized residual association with age, body size, and pubertal stage. Both
      the predicted mean and the predicted SD were modeled to account for
      heteroscedasticity. RESULTS: We identified nonlinear association of CRF
      parameters with body size and significant heteroscedasticity. To normalize CRF
      parameters, the use of a single body size variable was not sufficient. We
      therefore used multivariable models with various combination of height, corrected
      body mass, and age. Final prediction models yielded adjusted CRF parameters that
      were independent of age, sex, body mass, height, body mass index, and Tanner
      stages. CONCLUSIONS: We present Z score equations for several CRF parameters
      derived from a healthy pediatric population. These reference values provide
      updated predicted means and range of normality that are independent of sex and
      body size. Further testing is needed to assess if these reference values increase
      sensitivity and specificity to identify abnormal cardiorespiratory response in
      children with chronic diseases.

PMID- 29346168
TI  - A New Robot-assisted Billroth-I Reconstruction: Details of the Technique and
      Early Results.
AB  - BACKGROUND: Laparoscopic surgery for gastric tumor is considered a demanding
      procedure because of lymph node dissection and reconstruction. Billroth-I (B-I)
      reconstruction after laparoscopic distal gastrectomy is commonly performed
      extracorporeally because of the complexity of an intracorporeal procedure.
      Robotic surgery overcomes some limitations of laparoscopy, allowing to reproduce
      the basic maneuvers of open surgery. We describe a new technique to perform
      robotic B-I anastomosis. METHODS: Between January 2012 and February 2015, 5
      patients underwent distal gastrectomy with intracorporeal B-I-stapled
      anastomosis. Patient demographics, tumor characteristics, histopathologic
      features, and perioperative data were analyzed. RESULTS: Median operative time
      was 170 minutes (145 to 180 min). There were no conversions. Contrast swallow was
      routinely performed on the third postoperative day. Median postoperative
      hospitalization was 7 days (range: 6 to 8). No major complications or mortality
      were observed. CONCLUSIONS: Robotic distal gastrectomy with intracorporeal B-I
      anastomosis is a safe and promising technique in selected cases of gastric
      tumors.

PMID- 29346169
TI  - Sphenoid Dysplasia: A Rare Presentation of Infantile Myofibroma.
AB  - The authors report a case of isolated congenital orbital myofibroma causing
      sphenoid dysplasia and presenting as global restriction of extraocular motility
      and ptosis in a neonate. Sphenoid wing dysplasia is most commonly associated
      neurofibromatosis 1 but this patient had no evidence of neurofibromatosis on
      clinical examination and genetic testing. Congenital orbital myofibroma can have
      secondary effects on bone and likely the lesion was present early in development
      leading to aplasia of the sphenoid bone. To the best of the authors' knowledge,
      this is the first reported case of sphenoid wing aplasia secondary to congenital
      orbital myofibroma independent of neurofibromatosis 1.

PMID- 29346170
TI  - Apocrine Cystadenoma of the Eyelid: A Rare Palpebral Neoplasm. Report of 2 Cases.
AB  - The authors report 2 cases of apocrine cystadenoma of the eyelid, 1 of which was
      studied with immunohistochemical and other special stains. While a previous
      report describes the tumor in a palpebro-orbital location, no other detailed
      descriptions of a purely eyelid location are present in the literature. Apocrine
      cystadenoma occupies an unusual portion of the spectrum of Moll gland tumors of
      the eyelid. It has no definitive clinical characteristics and may be diagnosed
      pathologically by hematoxylin-eosin-stained sections.

PMID- 29346171
TI  - A Common Procedure With an Uncommon Pathology: Triamcinolone Acetonide Eyelid
      Injection.
AB  - Local corticosteroid injections are frequently employed by ophthalmologists to
      treat a variety of ocular, periocular, and orbital inflammatory conditions.
      Triamcinolone acetonide is a slowly dissolving crystalline corticosteroid that is
      often used for this purpose because of its prolonged anti-inflammatory effect. On
      occasion, previously injected corticosteroid material persists in tissues longer
      than anticipated, creating nodules that may masquerade as other disease
      conditions, or appearing incidentally in excised lesions on histopathologic
      examination. The histopathologic features of corticosteroid residues are
      unfamiliar to most ophthalmic pathologists and general pathologists. These
      features are described herein. Triamcinolone acetonide deposits in the skin
      appear as pale eosinophilic lakes of acellular frothy material on hematoxylin
      eosin staining and are occasionally surrounded by a mild inflammatory reaction.

PMID- 29346172
TI  - Apremilast Use in a Case of Cicatricial Ectropion Secondary to Severe Lamellar
      Ichthyosis.
AB  - Ichthyosis is a cutaneous disorder characterized by excessive amounts of dry
      thickened skin surface scales. Ocular manifestations of ichthyosis include
      cicatricial ectropion, which may cause exposure keratoconjunctivitis and rarely
      corneal perforation. Topical emollients, anti-inflammatory ointments, and
      systemic retinoids have been used to control the disease process, while surgical
      correction with donor graft has been reserved for severe cases involving corneal
      exposure. The authors report a case of a Caucasian male with lamellar ichthyosis
      with severe bilateral upper and lower eyelid cicatricial ectropion and corneal
      ulceration requiring surgical correction. Treatment with apremilast, a novel
      phosphodiesterase-4 inhibitor, for the treatment of a concomitant plaque
      psoriasis achieved good control of his skin diseases and minimized the recurrence
      of eyelid ectropion.

PMID- 29346173
TI  - The subresolution DaTSCAN phantom: a cost-effective, flexible alternative to
      traditional phantom technology.
AB  - The Alderson striatal phantom is frequently used to assess I-FP-CIT (Ioflupane)
      image quality and to test semi-quantification software. However, its design is
      associated with a number of limitations, in particular: unrealistic image
      appearances and inflexibility. A new physical phantom approach is proposed on the
      basis of subresolution phantom technology. The design incorporates thin slabs of
      attenuating material generated through additive manufacturing, and paper sheets
      with radioactive ink patterns printed on their surface, created with a
      conventional inkjet printer. The paper sheets and attenuating slabs are
      interleaved before scanning. Use of thin layers ensures that they cannot be
      individually resolved on reconstructed images. An investigation was carried out
      to demonstrate the performance of such a phantom in producing simplified I-FP-CIT
      uptake patterns. Single photon emission computed tomography imaging was carried
      out on an assembled phantom designed to mimic a healthy patient. Striatal binding
      ratio results and linear striatal dimensions were calculated from the
      reconstructed data and compared with that of 22 clinical patients without
      evidence of Parkinsonian syndrome, determined from clinical follow-up. Striatal
      binding ratio results for the fully assembled phantom were: 3.1, 3.3, 2.9 and 2.6
      for the right caudate, left caudate, right putamen and right caudate,
      respectively. All were within two SDs of results derived from a cohort of
      clinical patients. Medial-lateral and anterior-posterior dimensions of the
      simulated striata were also within the range of values seen in clinical data.
      This work provides the foundation for the generation of a range of more
      clinically realistic, physical phantoms.

PMID- 29346174
TI  - Tonal and vowel information processing in Chinese spoken word recognition: an
      event-related potential study.
AB  - In the present study, the time course of tonal and vowel information processing
      of the spoken words in Mandarin Chinese was investigated using a delayed-response
      paradigm. Idiomatic materials, providing semantically highly constraining
      contexts, were utilized. Besides being presented normally, the terminal
      monosyllabic words in idioms were manipulated with Tonal, Vowel, or Triple
      violations (i.e. with consonantal, tonal, and vowel mismatches). Event-related
      potential results showed that all three violations elicited larger widespread
      negativities in comparison with the Control condition, with the Triple violation
      effect starting first from 150 ms, then the Vowel violation, and the Tonal
      violation being the latest. The different starting times of the violation effects
      suggest that the access of tonal information is slower than that of vowel
      information, even though the lexical tones are very important in distinguishing
      the meaning of Chinese words.

PMID- 29346175
TI  - Long-Term Impacts Faced by Patients and Families After Harmful Healthcare Events.
AB  - BACKGROUND: Patients and families report experiencing a multitude of harms from
      medical errors resulting in physical, emotional, and financial hardships. Little
      is known about the duration and nature of these harms and the type of support
      needed to promote patient and family healing after such events. We sought to
      describe the long-term impacts (LTIs) reported by patients and family members who
      experienced harmful medical events 5 or more years ago. METHODS: We performed a
      content analysis on 32 interviews originally conducted with 72 patients or family
      members about their views of the factors contributing to their self-reported
      harmful event. Interviews selected occurred 5 or more years after the harmful
      event and were grouped by time since event, 5 to 9 years (22 interviews) or 10 or
      more years (10 interviews) for analysis. We analyzed these interviews targeting
      spontaneous references of ongoing impacts experienced by the participants.
      RESULTS: Participants collectively described the following four LTIs:
      psychological, social/behavioral, physical, and financial. Most cited
      psychological impacts with half-reporting ongoing anger and vivid memories. More
      than half reported ongoing physical impacts and one-third experienced ongoing
      financial impacts. Long-term social and behavioral impacts such as alterations in
      lifestyle, self-identity, and healthcare seeking behaviors were the most highly
      reported. CONCLUSIONS: These patients and families experienced many profound LTIs
      after their harmful medical event. For some, these impacts evolved into secondary
      harms ongoing 10 years and more after the event. Our results draw attention to
      the persistent impacts patients and families may experience long after harmful
      events and the need for future research to understand and support affected
      patients and families.

PMID- 29346176
TI  - Rapid Response: To Scan or Not to Scan? The Utility of Noncontrast CT Head for
      Altered Mental Status.
AB  - OBJECTIVES: The aims of the study were the following: (1) to determine how often
      computed tomography (CT) scans of the head are obtained on rapid responses called
      for altered mental status (AMS), (2) to determine whether CT imaging of the head
      is required during all rapid responses called for AMS, (3) to determine which
      patients would benefit from CT scans of the head in this setting, (4) to note
      whether an adequate neurologic exam was documented, (5) to determine the cost of
      CT scans that did not change management, and (6) to examine the role of
      medications leading to AMS. METHODS: The study was a retrospective chart review
      at Abington Jefferson Hospital. Data collected included the age, sex, time of
      rapid response, clinical condition of the patient, whether an arterial blood gas
      and blood glucose were done, and whether a neurological exam was documented in
      the resident's rapid response team note. The patient's medications were also
      reviewed. Computed tomography scan findings as well as changes made in a
      patient's care as a result of the scan were recorded. Any findings that did not
      lead to a change in management were considered a "negative" scan. RESULTS:
      Overall, 610 rapid responses were activated from January to August 2016. One
      hundred four (17.04%) of the total rapid responses were for AMS and 83 (79.8%) of
      these patients underwent noncontrast CT scan of the head. The mean (SD) age of
      the patients was 74.7 (13.6) years. A total of 56.6% were female. The most
      frequent clinical conditions documented at the time of rapid responses were noted
      as confused (33.7%, 28/83), either lethargic or unconscious (32.5%, 27/83), and
      concern for stroke (21.7%, 18/83). A total of 96.4% (80/83) of the CT scans done
      were negative for any acute changes. The three patients with positive scans
      (3/83) had a change in management as a result of the scans. If patients with
      symptoms concerning for stroke and unconscious patients are excluded, the total
      number of remaining patients is 56. Of these, zero patients had a positive scan.
      A total of 64.7% of the rapid response teams were activated either in the
      afternoon (31.3%) or at night (33.7%). A total of 33.7% had a complete
      neurological exam documented. A total of 66.2% were either incomplete (34.9%) or
      absent (31.3%). Sixty percent of the patients who had a CT head for AMS also had
      a blood sugar checked at bedside. Thirty-eight percent had an arterial blood gas.
      More than half the patients were taking one or more sedating medications (45/83,
      57.8%). Most patients were not on anticoagulants (79.5%). CONCLUSIONS: The
      findings of this study suggest that CT scan of the head is useful in older
      patients, patients with symptoms concerning for stroke, or cases of sudden onset
      of impaired consciousness. Noncontrast CT scans of the head are not useful for
      other presentations of AMS.

PMID- 29346177
TI  - No association between FOXP2 rs10447760 and schizophrenia in a replication study
      of the Chinese Han population.
AB  - BACKGROUND: Schizophrenia (SCZ) is a severe and heritable psychiatric disorder,
      and previous studies have shown that regulation of the forkhead-box P2 gene
      (FOXP2) may play a role in schizophrenia. Moreover, just a few studies have
      identified a single nucleotide polymorphism (SNP) rs10447760 within the gene that
      was a risk variant for SCZ in the Chinese Han population. METHODS: To examine
      whether the variant in the FOXP2 gene contributes toward SCZ susceptibility, we
      carried out an association analysis of the SNP rs10447760 of the FOXP2 gene in a
      case-control study (1405 cases, 1137 controls) from China. RESULTS: We identified
      no association of rs10447760 in the FOXP2 gene with SCZ (all P>0.05). In
      addition, a meta-analysis indicated that the SNP rs10447760 was not associated
      with susceptibility to SCZ in Han Chinese populations (pooled odds ratio=1.44,
      95% confidence interval: 0.63-3.31, P=0.39). CONCLUSION: Thus, our results did
      not support the association between FOXP2 rs10447760 and schizophrenia in a
      Chinese Han population, and large-scale genetic replication studies with
      different racial and geographic origins are required in the future.

PMID- 29346178
TI  - Multiple primary malignancies and prolonged survival in a patient with widespread
      metastatic cutaneous melanoma.

PMID- 29346179
TI  - Avstick: An Intravenous Catheter Insertion Simulator for Use with Standardized
      Patients.
AB  - An overwhelming majority of hospitalized patients undergo intravenous (IV)
      catheter insertion in order to receive hydration and necessary medication.
      Current IV insertion training techniques include manikins that are unable to
      react or give feedback to the trainee. The Avstick(r) is a realistic training
      device that can be worn by an actor, allowing a nurse trainee to perform an IV
      catheter insertion on a live patient without causing the person harm. The purpose
      of this study is to demonstrate the effectiveness of the Avstick in nursing
      education to increase nurse-patient communication and trainee self-efficacy.

PMID- 29346180
TI  - Development of a PD-L1 Complementary Diagnostic Immunohistochemistry Assay
      (SP142) for Atezolizumab.
AB  - Cancer immunotherapies, such as atezolizumab, are proving to be a valuable
      therapeutic strategy across indications, including non-small cell lung cancer
      (NSCLC) and urothelial cancer (UC). Here, we describe a diagnostic assay that
      measures programmed-death ligand 1 (PD-L1) expression, via immunohistochemistry,
      to identify patients who will derive the most benefit from treatment with
      atezolizumab, a humanized monoclonal anti-PD-L1 antibody. We describe the
      performance of the VENTANA PD-L1 (SP142) Assay in terms of specificity,
      sensitivity, and the ability to stain both tumor cells (TC) and tumor
      infiltrating immune cells (IC), in NSCLC and UC tissues. The reader precision,
      repeatability and intermediate precision, interlaboratory reproducibility, and
      the effectiveness of pathologist training on the assessment of PD-L1 staining on
      both TC and IC were evaluated. We detail the analytical validation of the VENTANA
      PD-L1 (SP142) Assay for PD-L1 expression in NSCLC and UC tissues and show that
      the assay reliably evaluated staining on both TC and IC across multiple
      expression levels/clinical cut-offs. The reader precision showed high overall
      agreement when compared with consensus scores. In addition, pathologists met the
      predefined training criteria (>=85.0% overall percent agreement) for the
      assessment of PD-L1 expression in NSCLC and UC tissues with an average overall
      percent agreement >=95.0%. The assay evaluates PD-L1 staining on both cell types
      and is robust and precise. In addition, it can help to identify those patients
      who may benefit the most from treatment with atezolizumab, although treatment
      benefit has been demonstrated in an all-comer NSCLC and UC patient
      population.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- 29346181
TI  - 34BetaE12 and Alfa-Methylacyl Coenzyme A Racemase (AMACR) Antibodies Better Than
      p63 Antibody Distinguish Normal and Neoplastic Glands in Prostatic Tissue With
      Thermal Artifacts.
AB  - The occurrence of inked margins with crush artifact derived from the
      electrocauterization in radical prostatectomy and/or the presence of crushed
      areas with distorted glands in prostatic samples after transurethral resection of
      prostate (TURP) can induce a significant interobserver variability during
      histopathologic evaluation of specimens. The specific immunostaining for basal
      cell markers 34BetaE12 and p63 and for alfa-methylacyl coenzyme A racemase
      (AMACR) in neoplastic cells is commonly used as an ancillary tool to establish
      benign and malignant glands. In this study we carried out the immunohistochemical
      reactions for p63, 34BetaE12, and AMACR on 3 different and successive paraffin
      sections to discriminate malignant and benign prostatic glands, distorted and
      crushed by the thermal artifacts in 60 radical prostatectomies and 50 TURP
      samples. All prostatic acinar adenocarcinoma showed the loss of basal cell
      markers and expression of AMACR, whereas p63 failed to stain the basal cell layer
      in benign crushed prostatic glands. The same cauterized glands were steadily
      positive for 34BetaE12. The high percentage of p63 false negative cases in benign
      distorted and crushed glands could be explained by the thermal artifacts which
      might cause lack of p63 antigenicity. In contrast, the antigenicity of 34BetaE12
      and AMACR seem not to be affected by cautery artifacts. Thus, in cauterized
      suspicious prostatic glands an immunohistochemistry panel including, p63,
      34BetaE12, and AMACR or only 34BetaE12 is recommended. In addition, after the
      first evaluation with only p63, we suggest that a separate and confirmatory
      staining for 34BetaE12 is strongly recommended.

PMID- 29346182
TI  - Atypical Teratoid Rhabdoid Tumor of the Cauda Equina in a Child: Report of a Very
      Unusual Case.
AB  - Atypical teratoid/rhabdoid tumors (AT/RT) are highly aggressive malignant
      primitive neoplasms that commonly occur in children younger than 2 years of age.
      The prognosis is generally dismal with a median survival time of <1 year. The
      majority of AT/RT occur in the posterior fossa and less frequently the
      supratentorium. Primary pediatric spinal AT/RT are exceedingly rare and only 15
      cases have been reported to date. Here we report a very unusual case of primary
      spinal AT/RT extensively involving the spinal cord from T11 down to the cauda
      equina. In this patient, the tumor was highly aggressive and resulted in
      extensive dissemination into the nerve roots and paraspinal soft tissue rapidly
      resulting in the patient's death 1 month after diagnosis. to the best of our
      knowledge, this degree of involvement of the spine by a primary AT/RT has not
      been described before.

PMID- 29346183
TI  - Near-infrared spectroscopy to predict organ failure and outcome in sepsis: the
      Assessing Risk in Sepsis using a Tissue Oxygen Saturation (ARISTOS) study.
AB  - OBJECTIVES: Sepsis is acute organ dysfunction in the setting of infection. An
      accurate diagnosis is important to guide treatment and disposition. Tissue oxygen
      saturation (StO2) can be estimated noninvasively by near-infrared spectroscopy
      (NIRS), and may be an indicator of microcirculatory dysfunction in early sepsis.
      We aimed to determine the utility of StO2 for sepsis recognition and outcome
      prediction among patients presenting to the emergency department (ED) with
      infection. PATIENTS AND METHODS: A multicentre, prospective, observational cohort
      study recruited patients who were being admitted to hospital with infection. StO2
      was measured in the ED using a handheld NIRS device, Inspectra 300. Outcomes were
      sepsis, defined as an increase in sequential organ failure assessment score of at
      least 2 points within 72 h, and composite in-hospital mortality/ICU admission at
      least 3 days. RESULTS: A cohort of 323 participants, median age 64 (interquartile
      range: 47-77) years, was recruited at three Australian hospitals. 143 (44%)
      fulfilled the criteria for sepsis and 22 (7%) died within 30 days. The mean+/-SD
      StO2 was 74+/-8% in sepsis and 78+/-7% in nonsepsis (P<0.0001). StO2 correlated
      with the peak sequential organ failure assessment score (Spearman's rho -0.27,
      P<0.0001). Area under the receiver operating characteristic curve was 0.66 (95%
      confidence interval: 0.60-0.72) for sepsis and 0.66 (0.58-0.75) for the composite
      outcome. StO2 less than 75% had an odds ratio of 2.67 (1.45-4.94; P=0.002), for
      the composite outcome compared with StO2 at least 75%. CONCLUSION: NIRS-derived
      StO2 correlates with organ failure and is associated with outcome in sepsis.
      However, its ability to differentiate sepsis among ED patients with infection is
      limited. NIRS cannot be recommended for this purpose.

PMID- 29346184
TI  - Synergistic Impact of Training Followed by On-Site Support on HIV Clinical
      Practice: A Mixed-Design Study in Uganda With Pre/Post and Cluster-Randomized
      Trial Components.
AB  - BACKGROUND: Task shifting can expand antiretroviral therapy access, but little is
      known about effective approaches to improve clinical practice among midlevel
      practitioners (MLPs) such as clinical officers, nurses, and midwives. The
      Integrated Infectious Diseases Capacity Building Evaluation compared training
      alone with training combined with on-site support (OSS). METHODS: Two MLPs each
      from 36 health facilities attended the 5-week Integrated Management of Infectious
      Disease training. After training, 18 facilities randomly assigned to arm A
      received OSS for 9 months, whereas 18 arm B facilities did not. Clinical faculty
      assessed MLP HIV clinical practice on 6 tasks: history taking, physical
      examination, laboratory investigations, diagnosis, treatment, and patient
      education. We analyzed the effect of training alone and training combined with
      OSS as the pre/post change within each arm. We analyzed the incremental effect of
      OSS with a difference-in-difference analysis that compared changes between arms.
      RESULTS: Training alone and training combined with OSS significantly improved
      clinical practice in patient history taking (13% and 24% increase, respectively),
      physical examination (54% and 71%), laboratory investigations (32% and 20%), and
      diagnosis (31% and 51%). Combined training and OSS also improved patient
      education significantly (72% increase). Effect sizes for training combined with
      OSS were larger than for training alone except for laboratory investigations, and
      the effects were robust in sensitivity analyses. The incremental effect of OSS on
      diagnosis was significant [adjusted relative risk = 1.23; 95% confidence interval
      = 1.00 to 1.50]. CONCLUSIONS: Combined training and OSS improved MLP HIV clinical
      practice over training alone and can contribute to continued expansion of access
      to antiretroviral therapy.

PMID- 29346185
TI  - Brief Report: Higher ART Adherence Is Associated With Lower Systemic Inflammation
      in Treatment-Naive Ugandans Who Achieve Virologic Suppression.
AB  - BACKGROUND: Residual systemic inflammation persists despite suppressive
      antiretroviral therapy (ART) and is associated with non-AIDS clinical outcomes.
      We aimed to evaluate the association between ART adherence and inflammation in
      Ugandans living with HIV who were predominantly receiving nevirapine-based ART
      with a thymidine analog backbone and were virologically suppressed by
      conventional assays. METHODS: Plasma concentrations of interleukin-6 (IL-6), D
      dimer, soluble (s)CD14, sCD163, and the kynurenine/tryptophan ratio, in addition
      to CD8 T-cell activation, were measured at baseline and 6 months after ART
      initiation in treatment-naive adults who achieved an undetectable plasma HIV RNA
      (<400 copies/mL) at their 6-month visit. Adherence was measured through
      medication event monitoring system and calculated as the ratio of
      observed/prescribed device openings per participant. We fit adjusted linear
      regression models to estimate the association between ART adherence and the log
      transformed plasma concentrations of inflammatory biomarkers. RESULTS: We
      evaluated 282 participants (median age, 35 years; 70% women). The median
      (interquartile range) adherence was 93% (84-98). In the adjusted analyses, for
      every 10% increase in average ART adherence, we found a 15% [P < 0.0001; 95%
      confidence interval (CI), -21.0 to -7.9], 11% (P = 0.017; 95% CI, -18.3 to -2.0),
      and 3% (P = 0.028; 95% CI, -5.0 to -0.3) decrease in IL-6, D-dimer, and sCD14,
      respectively. CONCLUSIONS: Higher ART adherence was associated with lower levels
      of biomarkers of inflammation, immune activation, and coagulopathy among Ugandans
      living with HIV who achieved viral suppression shortly after ART initiation. This
      suggests that ART adherence could have biological consequences beyond viral
      suppression. Whether ART adherence optimization in virologically suppressed
      individuals could reduce residual inflammation remains unknown.

PMID- 29346186
TI  - Fall Rates in Urban and Rural Nursing Units: Does Location Matter?
AB  - Patient falls remain a leading adverse event in hospitals. In a study of 65 rural
      hospitals with 222 nursing units and 560 urban hospitals with 4274 nursing units,
      we found that geographic region, unit type, and nurse staffing, education,
      experience, and outcomes were associated with fall rates. Implications include
      specific attention to fall prevention in rehabilitation units, creating better
      work environments that promote nurse retention, and provide RN-BSN educational
      opportunities.

PMID- 29346187
TI  - Quality in Postoperative Patient Handover: Different Perceptions of Quality
      Between Transferring and Receiving Nurses.
AB  - BACKGROUND: A safe and efficient patient handover is important to ensure high
      quality patient care and reduce the risk of patient harm. Few studies have
      explored handover activities beyond information transfer. PURPOSE: The aims were
      to assess overall postoperative handover quality and relate quality assessments
      to handover circumstances, conduct, and teamwork and to compare transferring and
      receiving nurses' evaluations of handover quality. METHOD: This was a cross
      sectional study using the Norwegian Handover Quality Rating Form (N-HQRF). In
      addition, data were collected on nurses' evaluations of the patient condition,
      handover preparation, and participating nurses' clinical experience. RESULTS:
      Although total perceived handover quality was high in a large majority of cases,
      there were significant differences between transferring and receiving nurses'
      evaluations of the same handover. Lower-quality handovers had a higher frequency
      of time pressure, uncertainty, and patient-related problems. CONCLUSION: The
      findings point to the need to assess handover quality in a wider perspective.
      Handover circumstances might impact handover quality and should be considered
      when procedures for handover quality are designed and implemented.

PMID- 29346188
TI  - Evaluation of Role Acquisition and Preparation for the CNL Certification
      Examination Through an Online Immersion Course.

PMID- 29346190
TI  - Why Don't Hospitals Prioritize Substance Abuse in Their Community Benefit
      Programming?
AB  - The goal of this study was to understand whether Appalachian Ohio hospitals
      prioritized substance abuse in their IRS-mandated community health needs
      assessments (CHNAs) and if not, what factors were important in this decision.
      Analysis of CHNA reports from all 28 hospitals in the region supplemented
      interview data from in-depth phone interviews, with 17 participants tasked with
      overseeing CHNAs at 21 hospitals. The CHNA reports show that hospitals in this
      region prioritize substance abuse and mental health less often than access to
      care and obesity. Interviews suggest 4 reasons: lack of resources, risk aversion,
      concern about hospital expertise, and stigma related to substance abuse.
      Hospitals are playing a larger role in public health as a result of CHNA
      requirements but resist taking on challenging problems such as substance abuse.
      The report concludes by summarizing concrete steps to ensure that community
      benefit efforts address pressing health problems. The implications of this study
      are manifest in concrete recommendations for encouraging hospitals to address
      pressing health problems in their community benefit efforts.

PMID- 29346191
TI  - The Four Corners Sign: A Specific Imaging Feature in Differentiating Systemic
      Sclerosis-related Interstitial Lung Disease From Idiopathic Pulmonary Fibrosis.
AB  - PURPOSE: Differentiating between systemic sclerosis-related interstitial lung
      disease (SSc-ILD) and idiopathic pulmonary fibrosis (IPF) is important because of
      the differences in workup, prognosis, and treatment. However, there is much
      overlap in the appearance of these 2 entities on high-resolution computed
      tomography. We propose that inflammation and/or fibrosis focally or
      disproportionately involving the bilateral anterolateral upper lobes and
      posterosuperior lower lobes ["Four Corners" Sign (FCS)] is specific for SSc-ILD.
      MATERIALS AND METHODS: Randomized high-resolution computed tomography studies
      from 74 IPF and 73 SSc-ILD cases were evaluated by 2 thoracic radiologists
      blinded to all patient data. For each case the reviewers noted whether the FCS
      was present and assigned a confidence level on the basis of a 7-point Likert
      scale. The same process was then performed on a randomized external validation
      group of 42 SSc-ILD and 42 IPF cases. RESULTS: For Likert scores of 6 or 7
      ("mostly agree" or "entirely agree" that the FCS is present, respectively) the
      sensitivity in SSc was 16.4% (95% confidence interval, 9.7%, 26.6%), specificity
      100.0% (95% confidence interval, 95.1%, 100.0%). There was a significant
      association between a confidently present FCS and SSc compared with a confidently
      present FCS and IPF (P=0.0003). Analysis on an external validation group of 42
      SSc and 42 IPF cases conferred similarly high specificity for SSc in cases
      characterized as FCS with high confidence. CONCLUSION: The FCS, a pattern of
      focal or disproportionate inflammation and/or fibrosis involving the bilateral
      anterolateral upper lobes and posterosuperior lower lobes, is specific for SSc
      ILD when readers are confident of its presence.

PMID- 29346189
TI  - The Impact of Implementing Tobacco Control Policies: The 2017 Tobacco Control
      Policy Scorecard.
AB  - The Tobacco Control Scorecard, published in 2004, presented estimates of the
      effectiveness of different policies on smoking rates. Since its publication, new
      evidence has emerged. We update the Scorecard to include recent studies of demand
      reducing tobacco policies for high-income countries. We include cigarette taxes,
      smoke-free air laws, media campaigns, comprehensive tobacco control programs,
      marketing bans, health warnings, and cessation treatment policies. To update the
      2004 Scorecard, a narrative review was conducted on reviews and studies published
      after 2000, with additional focus on 3 policies in which previous evidence was
      limited: tobacco control programs, graphic health warnings, and marketing bans.
      We consider evaluation studies that measured the effects of policies on smoking
      behaviors. Based on these findings, we derive estimates of short-term and long
      term policy effect sizes. Cigarette taxes, smoke-free air laws, marketing
      restrictions, and comprehensive tobacco control programs are each found to play
      important roles in reducing smoking prevalence. Cessation treatment policies and
      graphic health warnings also reduce smoking and, when combined with policies that
      increase quit attempts, can improve quit success. The effect sizes are broadly
      consistent with those previously reported for the 2004 Scorecard but now reflect
      the larger evidence base evaluating the impact of health warnings and advertising
      restrictions.

PMID- 29346192
TI  - Image Quality, Overall Evaluability, and Effective Radiation Dose of Coronary
      Computed Tomography Angiography With Prospective Electrocardiographic Triggering
      Plus Intracycle Motion Correction Algorithm in Patients With a Heart Rate Over 65
      Beats Per Minute.
AB  - PURPOSE: Recently, a new intracycle motion correction algorithm (MCA) was
      introduced to reduce motion artifacts from heart rate (HR) in coronary computed
      tomography angiography (cCTA). The aim of the study was to evaluate the image
      quality, overall evaluability, and effective radiation dose (ED) of cCTA with
      prospective electrocardiographic (ECG) triggering plus MCA as compared with
      standard protocol with retrospective ECG triggering in patients with HR>=65 bpm.
      MATERIALS AND METHODS: One hundred consecutive patients (67+/-10 y) scheduled for
      cCTA with 65<HR<80 bpm were retrospectively analyzed. The patients were assigned
      to 2 groups undergoing prospective (group 1) or retrospective (group 2) triggered
      cCTA. The study protocol was approved by the Institutional Ethics Committee and a
      written informed consent was obtained from all patients. Image noise, signal to
      noise ratio, contrast to noise ratio, Likert image quality score (score 1,
      nondiagnostic; score 2, adequate; score 3, good; score 4, excellent), overall
      image evaluability, and ED were measured and compared between the 2 groups. Both
      vessel-based and patient-based analyses were evaluated. Student test or Wilcoxon
      test were used to evaluate differences of continuous variables, whereas the chi
      test was used to study differences with regard to categorical data. A P-value
      <0.05 was considered statistically significant. RESULTS: cCTA was successfully
      performed in all patients. In a segment-based model, group 1 compared with group
      2 showed a lower rate of overall artifacts (67% vs. 83%; P<0.001) and motion
      artifacts (49% vs. 66%; P<0.001), resulting in a better Likert image quality
      score (2.83+/-1.03 vs. 2.37+/-1.02; P<0.01) and overall evaluability (85% vs.
      75%; P<0.01). Group 1 showed a lower ED as compared with group 2 (3.1+/-1.9 vs.
      11.9+/-3.3 mSv; P<0.01). CONCLUSION: MCA and cCTA with prospective ECG-triggering
      acquisition in patients with high HR improves image quality and overall
      evaluability compared with cCTA with standard retrospective ECG triggering.

PMID- 29346193
TI  - Perceptions of Infection Risk With Immunomodulatory Medications.
AB  - OBJECTIVES: Physicians of many specialties encounter patients treated with
      immunomodulatory medications and must weigh the risk of infection when making
      medical decisions. We explored how physician perceptions of the infection risk of
      immunomodulatory medications differ by specialty and level of experience.
      METHODS: A survey was distributed to physicians from the internal medicine,
      family medicine, emergency medicine, rheumatology, dermatology, and infectious
      disease departments at 1 tertiary care institution. Physicians scored their level
      of concern for the risk of infection of 15 commonly used immunomodulatory
      medications hypothetically taken for 1 year. RESULTS: The survey was distributed
      to 634 people; 197 physicians completed the survey. Opinion of the risk of
      infection differed significantly by specialty for 8 of 15 medications.
      Experienced providers rated risk of infection differently from less experienced
      providers for prednisone 10 to 20 mg (P = 0.046), hydroxychloroquine (P = 0.013),
      dapsone (P = 0.029), and anti-tumor necrosis factor (TNF) therapy (P = 0.027).
      Most experienced physicians regarded dapsone (95%) and hydroxychloroquine (93%)
      as low risk, whereas many less experienced physicians scored them as medium- or
      high-risk medications. In contrast, experienced physicians were more likely to
      rate prednisone 10 to 20 mg as medium or high risk. Most less experienced
      physicians (55%) identified anti-TNF therapy as high risk, whereas experienced
      physicians were split evenly among low, medium, and high risk. CONCLUSIONS: There
      is substantial variability in physician perception of the risk of infection of
      many immunomodulatory medications. Experienced physicians are more concerned than
      peers about the risk of infection of intermediate doses of prednisone. Opinions
      regarding anti-TNF therapy range broadly even among experienced providers.

PMID- 29346194
TI  - A Radiographic Double Contour Sign Mimicking Pseudogout.

PMID- 29346195
TI  - The Entheseal Signature of Erosive Arthritis: Surface Microscopy of Achilles
      Tendon Insertions Into Bone.

PMID- 29346197
TI  - From Foundation to Demolition: The Influence of Perioperative Tranexamic Acid.

PMID- 29346196
TI  - Effectiveness of CenteringPregnancy on Breastfeeding Initiation Among African
      Americans: A Systematic Review and Meta-analysis.
AB  - While breastfeeding initiation rates for African American mothers are low, an
      innovative model of group prenatal care, CenteringPregnancy, holds promise to
      increase breastfeeding rates. The aim of this systematic review and meta-analysis
      was to examine the effects of CenteringPregnancy versus individual prenatal care
      on breastfeeding initiation among African American mothers. Using a systematic
      approach and PRISMA guidelines, 4 electronic databases were used to search the
      literature. English-language studies, comparing CenteringPregnancy and individual
      prenatal care, including African American participants, and specifying
      breastfeeding initiation as an outcome were screened for inclusion. Study
      strength and quality were assessed and 7 studies were systematically reviewed and
      meta-analyzed. Participation in CenteringPregnancy increased the probability of
      breastfeeding initiation by 53% (95% confidence interval = 29%-81%) (n = 8047). A
      subgroup analysis of breastfeeding initiation among only African American
      participants was performed on 4 studies where data were available. Participation
      in CenteringPregnancy increased the probability of breastfeeding initiation by
      71% (95% confidence interval = 27%-131%) (n = 1458) for African American
      participants. CenteringPregnancy is an effective intervention to increase
      breastfeeding initiation for participants, especially for African Americans. To
      close the racial gap in breastfeeding initiation, high-quality research providing
      specific outcomes for African American participants in CenteringPregnancy are
      needed.

PMID- 29346198
TI  - A Tale of Two Solutions: High vs Low-Chloride Intravenous Fluids.

PMID- 29346199
TI  - "Mirror, Mirror on the Wall": Learning From Reflections on Quality.

PMID- 29346200
TI  - A Novel Approach to Synthesize the Evidence on Analgesic Adjuvants for
      Postoperative Pain.

PMID- 29346201
TI  - Learning From Human Factors Can Make Anesthesia Even Safer.

PMID- 29346202
TI  - Ischemic Preconditioning and the Role of Antifibrinolytic Drugs: Translation From
      Bench to Bedside.

PMID- 29346203
TI  - Emergency General Surgery: Time for Anesthesiology and Surgery to Work Together
      to Drive Improvement in Outcomes.

PMID- 29346204
TI  - New Diabetes Medications Raise New Perioperative Concerns for the
      Anesthesiologist.

PMID- 29346205
TI  - "That's Not What I Said": Seeking Fidelity in Citations.

PMID- 29346206
TI  - Disparities in Anesthesia Care.

PMID- 29346207
TI  - Population Health Management and Perioperative Medicine: The Expanding Role of
      the Anesthesiologist.

PMID- 29346208
TI  - Surveying the Literature: Synopsis of Recent Key Publications.

PMID- 29346209
TI  - The Society of Thoracic Surgeons, The Society of Cardiovascular
      Anesthesiologists, and The American Society of ExtraCorporeal Technology:
      Clinical Practice Guidelines-Anticoagulation During Cardiopulmonary Bypass.
AB  - Despite more than a half century of "safe" cardiopulmonary bypass (CPB), the
      evidence base surrounding the conduct of anticoagulation therapy for CPB has not
      been organized into a succinct guideline. For this and other reasons, there is
      enormous practice variability relating to the use and dosing of heparin,
      monitoring heparin anticoagulation, reversal of anticoagulation, and the use of
      alternative anticoagulants. To address this and other gaps, The Society of
      Thoracic Surgeons, the Society of Cardiovascular Anesthesiologists, and the
      American Society of Extracorporeal Technology developed an Evidence Based
      Workgroup. This was a group of interdisciplinary professionals gathered to
      summarize the evidence and create practice recommendations for various aspects of
      CPB. To date, anticoagulation practices in CPB have not been standardized in
      accordance with the evidence base. This clinical practice guideline was written
      with the intent to fill the evidence gap and to establish best practices in
      anticoagulation therapy for CPB using the available evidence. To identify
      relevant evidence, a systematic review was outlined and literature searches were
      conducted in PubMed using standardized medical subject heading (MeSH) terms from
      the National Library of Medicine list of search terms. Search dates were
      inclusive of January 2000 to December 2015. The search yielded 833 abstracts,
      which were reviewed by two independent reviewers. Once accepted into the full
      manuscript review stage, two members of the writing group evaluated each of 286
      full papers for inclusion eligibility into the guideline document. Ninety-six
      manuscripts were included in the final review. In addition, 17 manuscripts
      published before 2000 were included to provide method, context, or additional
      supporting evidence for the recommendations as these papers were considered
      sentinel publications. Members of the writing group wrote and developed
      recommendations based on review of the articles obtained and achieved more than
      two thirds agreement on each recommendation. The quality of information for a
      given recommendation allowed assessment of the level of evidence as recommended
      by the American College of Cardiology Foundation/American Heart Association Task
      Force on Practice Guidelines. Recommendations were written in the three following
      areas: (1) heparin dosing and monitoring for initiation and maintenance of CPB;
      (2) heparin contraindications and heparin alternatives; and (3) reversal of
      anticoagulation during cardiac operations. It is hoped that this guideline will
      serve as a resource and will stimulate investigators to conduct more research and
      to expand on the evidence base on the topic of anticoagulation therapy for CPB.

PMID- 29346210
TI  - Significance, Errors, Power, and Sample Size: The Blocking and Tackling of
      Statistics.
AB  - Inferential statistics relies heavily on the central limit theorem and the
      related law of large numbers. According to the central limit theorem, regardless
      of the distribution of the source population, a sample estimate of that
      population will have a normal distribution, but only if the sample is large
      enough. The related law of large numbers holds that the central limit theorem is
      valid as random samples become large enough, usually defined as an n >= 30. In
      research-related hypothesis testing, the term "statistically significant" is used
      to describe when an observed difference or association has met a certain
      threshold. This significance threshold or cut-point is denoted as alpha (alpha)
      and is typically set at .05. When the observed P value is less than alpha, one
      rejects the null hypothesis (Ho) and accepts the alternative. Clinical
      significance is even more important than statistical significance, so treatment
      effect estimates and confidence intervals should be regularly reported. A type I
      error occurs when the Ho of no difference or no association is rejected, when in
      fact the Ho is true. A type II error occurs when the Ho is not rejected, when in
      fact there is a true population effect. Power is the probability of detecting a
      true difference, effect, or association if it truly exists. Sample size
      justification and power analysis are key elements of a study design. Ethical
      concerns arise when studies are poorly planned or underpowered. When calculating
      sample size for comparing groups, 4 quantities are needed: alpha, type II error,
      the difference or effect of interest, and the estimated variability of the
      outcome variable. Sample size increases for increasing variability and power, and
      for decreasing alpha and decreasing difference to detect. Sample size for a given
      relative reduction in proportions depends heavily on the proportion in the
      control group itself, and increases as the proportion decreases. Sample size for
      single-group studies estimating an unknown parameter is based on the desired
      precision of the estimate. Interim analyses assessing for efficacy and/or
      futility are great tools to save time and money, as well as allow science to
      progress faster, but are only 1 component considered when a decision to stop or
      continue a trial is made.

PMID- 29346211
TI  - Intratidal Analysis of Intraoperative Respiratory System Mechanics.

PMID- 29346212
TI  - Intratidal Analysis of Intraoperative Respiratory System Mechanics: Keep it
      Simple.

PMID- 29346213
TI  - Self-Esteem and Anger in Borderline Patients With Self-Injury Behavior.
AB  - Anger and low self-esteem characterize borderline individuals, yet little is
      known about their role and impact in the presence or absence of self-injury
      behavior. The present study aimed to investigate the impact of anger and self
      esteem in borderline patients and whether these variables distinguish these
      patients with and without self-injury. Patients were recruited from a psychiatric
      service and were evaluated for self-esteem and anger. Additionally, impulsivity
      and symptoms were assessed. Two groups were compared, one with self-injurious
      behavior (n = 18) and another one without it (n = 23). Those who injure
      themselves seem to have a lower self-esteem (p < 0.001), yet the strengthening of
      self-esteem seems to have different outcomes, according to the presence or
      absence of self-injury. Anger and self-esteem seem to influence the severity of
      diagnosis, but only in patients who self-injure. Anger and self-esteem may
      influence borderline patients differently according to the presence or absence of
      self-injury.

PMID- 29346214
TI  - Validation of Biomarkers for Early Detection of Pancreatic Cancer: Summary of The
      Alliance of Pancreatic Cancer Consortia for Biomarkers for Early Detection
      Workshop.
AB  - Pancreatic cancer is the third leading cause of cancer death in the United
      States, and the 5-year relative survival for patients diagnosed with pancreatic
      cancer is less than 10%. Early intervention is the key to a better survival
      outcome. Currently, there are no biomarkers that can reliably detect pancreatic
      cancer at an early stage or identify precursors that are destined to progress to
      malignancy. The National Cancer Institute in partnership with the Kenner Family
      Research Fund and the Pancreatic Cancer Action Network convened a Data Jamboree
      on Biomarkers workshop on December 5, 2016, to discuss and evaluate existing or
      newly developed biomarkers and imaging methods for early detection of pancreatic
      cancer. The primary goal of this workshop was to determine if there are any
      promising biomarkers for early detection of pancreatic cancer that are ready for
      clinical validation. The Alliance of Pancreatic Cancer Consortia for Biomarkers
      for Early Detection, formed under the auspices of this workshop, will provide the
      common platform and the resources necessary for validation. Although none of the
      biomarkers evaluated seemed ready for a large-scale biomarker validation trial, a
      number of them had sufficiently high sensitivity and specificity to warrant
      additional research, especially if combined with other biomarkers to form a
      panel.

PMID- 29346215
TI  - Challenges and Perspectives for Immunotherapy in Adenocarcinoma of the Pancreas:
      The Cancer Immunity Cycle.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with a devastating 5
      year overall survival of only approximately 7%. Although just 4% of all malignant
      diseases are accounted to PDAC, it will become the second leading cause of cancer
      related deaths before 2030. Immunotherapy has proven to be a promising
      therapeutic option in various malignancies such as melanoma, non-small cell lung
      cancer (NSCLC), microsatellite instability-high gastrointestinal cancer, urinary
      tract cancer, kidney cancer, and others. In this review, we summarize recent
      findings about immunological aspects of PDAC with the focus on the proposed model
      of the "cancer immunity cycle". By this model, a deeper understanding of the
      underlying mechanism in achieving a T-cell response against cancer cells is
      provided. There is currently great interest in the field around designing novel
      immunotherapy combination studies for PDAC based on a sound understanding of the
      underlying immunobiology.

PMID- 29346217
TI  - Pathological and Molecular Aspects to Improve Endoscopic Ultrasonography-Guided
      Fine-Needle Aspiration From Solid Pancreatic Lesions.
AB  - Endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) has been
      applied to pancreatic lesions since the 1990s, and its use is now widespread.
      Improvements in endoscopic devices and sampling techniques have resulted in
      excellent diagnostic ability for solid pancreatic lesions. However, clinical
      improvements alone are not responsible for it; pathological aspects have also
      played important roles. Rapid on-site evaluation minimizes endoscopic procedures,
      although its value at improving the diagnostic ratio is still debated. Diagnostic
      efficacy differs by sample preparations (direct smear, cytospin, liquid-based
      cytology, cell block, and biopsy) and by staining methods (Papanicoloau, Diff
      Quik, hematoxylin-eosin, and Giemsa). Several immunocytochemistry protocols aid
      in diagnosing epithelial components with cytological atypia and in
      differentiating various tumor types. One cytopathology diagnostic system is
      telecytology, which uses transmitted digital images and enables real-time
      diagnosis of EUS-FNA samples by expert cytologists at remote locations. However,
      EUS-FNA samples are useful for more than just diagnoses, as molecular analysis of
      these samples allows the identification of prognostic markers, such as genetic
      alterations in K-ras and EGFR. Expression of drug-metabolizing enzymes, human
      equilibrative nucleoside transporter 1, correlates with the response to
      gemcitabine-based chemotherapy. These pathology efforts have enhanced the
      diagnostic efficacy of EUS-FNA, thereby leading to better outcomes for patients
      with pancreatic diseases.

PMID- 29346216
TI  - Obesity and Pancreatic Cancer: Overview of Epidemiology and Potential Prevention
      by Weight Loss.
AB  - Currently, there are no effective preventive strategies for pancreatic cancer.
      Obesity has been increasingly recognized as a strong but modifiable risk factor
      of pancreatic cancer. In this article, we aim to review the literature regarding
      weight loss on prevention of pancreatic cancer. Epidemiological and laboratory
      studies have shown that obesity is associated with increased incidence of
      pancreatic cancer and potentially worse cancer outcome. Whereas the underlying
      pathomechanisms remain unclear, chronic inflammation, insulin resistance, and
      altered intestinal microbiota are all implicated in the carcinogenic effect of
      obesity. Weight loss, especially the durable and significant weight loss after
      bariatric surgery, has been shown to reduce the risks of multiple cancers and may
      become a good intervention for pancreatic cancer prevention.

PMID- 29346218
TI  - Predicting Pancreatitis Phenotype Based on a Shared Genotype.

PMID- 29346219
TI  - Pancreatic Metastases as the Initial Manifestation of a Neuroendocrine Carcinoma
      of the Uterine Cervix.

PMID- 29346220
TI  - TRO40303 Ameliorates Alcohol-Induced Pancreatitis Through Reduction of Fatty Acid
      Ethyl Ester-Induced Mitochondrial Injury and Necrotic Cell Death: Erratum.

PMID- 29346221
TI  - A Validation Argument for a Simulation-Based Training Course Centered on
      Assessment, Recognition, and Early Management of Pediatric Sepsis.
AB  - INTRODUCTION: Early recognition of sepsis remains one of the greatest challenges
      in medicine. Novice clinicians are often responsible for the recognition of
      sepsis and the initiation of urgent management. The aim of this study was to
      create a validity argument for the use of a simulation-based training course
      centered on assessment, recognition, and early management of sepsis in a
      laboratory-based setting. METHODS: Five unique simulation scenarios were
      developed integrating critical sepsis cues identified through qualitative
      interviewing. Scenarios were piloted with groups of novice, intermediate, and
      expert pediatric physicians. The primary outcome was physician recognition of
      sepsis, measured with an adapted situation awareness global assessment tool.
      Secondary outcomes were physician compliance with pediatric advanced life support
      (PALS) guidelines and early sepsis management (ESM) recommendations, measured by
      two internally derived tools. Analysis compared recognition of sepsis by levels
      of expertise and measured association of sepsis recognition with the secondary
      outcomes. RESULTS: Eighteen physicians were recruited, six per study group. Each
      physician completed three sepsis simulations. Sepsis was recognized in 19 (35%)
      of 54 simulations. The odds that experts recognized sepsis was 2.6 [95%
      confidence interval (CI) = 0.5-13.8] times greater than novices. Adjusted for
      severity, for every point increase in the PALS global performance score, the odds
      that sepsis was recognized increased by 11.3 (95% CI = 3.1-41.4). Similarly, the
      odds ratio for the PALS checklist score was 1.5 (95% CI = 0.8-2.6). Adjusted for
      severity and level of expertise, the odds of recognizing sepsis was associated
      with an increase in the ESM checklist score of 1.8 (95% CI = 0.9-3.6) and an
      increase in ESM global performance score of 4.1 (95% CI = 1.7-10.0). CONCLUSIONS:
      Although incomplete, evidence from initial testing suggests that the simulations
      of pediatric sepsis were sufficiently valid to justify their use in training
      novice pediatric physicians in the assessment, recognition, and management of
      pediatric sepsis.

PMID- 29346222
TI  - "To Err Is Human" but Disclosure Must be Taught: A Simulation-Based Assessment
      Study.
AB  - INTRODUCTION: Although error disclosure is critical in promoting safety and
      patient-centered care, physicians are inconsistently trained in its practice, and
      few objective methods to assess competence exist. We used an immersive simulation
      scenario to determine whether providers with varying levels of clinical
      experience adhere to the disclosure safe practice guidelines when exposed to a
      serious adverse event simulation scenario. METHODS: This was a prospective cohort
      study with medical students, junior emergency medicine (EM) residents (PGY 1-2),
      senior EM residents (PGY 3-4), and attending EM physicians participating in a
      simulated case in which a scripted medication overdose resulted in an adverse
      event. Each scenario was videotaped and scored by two expert raters based on a 6
      component, 21-point disclosure assessment instrument. RESULTS: There were 12
      participants in each study group (N = 48). There was good interrater reliability
      (kappa = 0.70). Total scores improved significantly as the level of training
      increased: medical student = 10.3 (2.7), PGY 1-2 = 12.3 (6.2), PGY 3-4 = 13.7
      (3.2), and attending physicians = 12.8 (3.7) (P = 0.03). Seventy-five percent of
      participants did not address preventing recurrence of the error. Fifty-six
      percent offered no apology or only offered it with prompting from the patient;
      only 23% offered an apology with the initial disclosure. CONCLUSIONS: We
      demonstrated suboptimal adherence to best practices guidelines for error
      disclosure when providers are assessed in an immersive simulation setting.
      Despite a correlation in performance of medical error disclosure with increased
      physician experience, this study suggests that healthcare providers may need
      additional training to comply with safe practice guidelines for disclosure of
      unanticipated adverse events.

PMID- 29346223
TI  - Learner-Adaptive Educational Technology for Simulation in Healthcare: Foundations
      and Opportunities.
AB  - STATEMENT: Despite evidence that learners vary greatly in their learning needs,
      practical constraints tend to favor ''one-size-fits-all'' educational approaches,
      in simulation-based education as elsewhere. Adaptive educational technologies -
      devices and/or software applications that capture and analyze relevant data about
      learners to select and present individually tailored learning stimuli - are a
      promising aid in learners' and educators' efforts to provide learning experiences
      that meet individual needs. In this article, we summarize and build upon the 2017
      Society for Simulation in Healthcare Research Summit panel discussion on adaptive
      learning. First, we consider the role of adaptivity in learning broadly. We then
      outline the basic functions that adaptive learning technologies must implement
      and the unique affordances and challenges of technology-based approaches for
      those functions, sharing an illustrative example from healthcare simulation.
      Finally, we consider future directions for accelerating research, development,
      and deployment of effective adaptive educational technology and techniques in
      healthcare simulation.

PMID- 29346224
TI  - Tipping the Scales: Prioritizing Mentorship and Support in Simulation Faculty
      Development.

PMID- 29346225
TI  - Validating Lung Models Using the ASL 5000 Breathing Simulator.
AB  - OBJECTIVE: This study sought to validate pediatric models with normal and altered
      pulmonary mechanics. METHODS: PubMed and CINAHL databases were searched for
      studies directly measuring pulmonary mechanics of healthy infants and children,
      infants with severe bronchopulmonary dysplasia and neuromuscular disease. The ASL
      5000 was used to construct models using tidal volume (VT), inspiratory time (TI),
      respiratory rate, resistance, compliance, and esophageal pressure gleaned from
      literature. Data were collected for a 1-minute period and repeated three times
      for each model. t tests compared modeled data with data abstracted from the
      literature. Repeated measures analyses evaluated model performance over multiple
      iterations. Statistical significance was established at a P value of less than
      0.05. RESULTS: Maximum differences of means (experimental iteration mean -
      clinical standard mean) for TI and VT are the following: term infant without lung
      disease (TI = 0.09 s, VT = 0.29 mL), severe bronchopulmonary dysplasia (TI = 0.08
      s, VT = 0.17 mL), child without lung disease (TI = 0.10 s, VT = 0.17 mL), and
      child with neuromuscular disease (TI = 0.09 s, VT = 0.57 mL). One-sample testing
      demonstrated statistically significant differences between clinical controls and
      VT and TI values produced by the ASL 5000 for each iteration and model (P <
      0.01). The greatest magnitude of differences was negligible (VT < 1.6%, TI = 18%)
      and not clinically relevant. CONCLUSIONS: Inconsistencies occurred with the
      models constructed on the ASL 5000. It was deemed accurate for the study
      purposes. It is therefore essential to test models and evaluate magnitude of
      differences before use.

PMID- 29346226
TI  - Preparing Physiotherapy Students for Clinical Placement: Student Perceptions of
      Low-Cost Peer Simulation. A Mixed-Methods Study.
AB  - INTRODUCTION: Simulation is increasingly used in health care education, yet the
      organizational and financial costs can be prohibitive. This study aimed to
      investigate whether peer simulation is perceived by third-year undergraduate
      physiotherapy students as valuable for clinical placement preparation. METHODS:
      Third-year undergraduate physiotherapy students participated in a 9-week peer
      simulation program, using each other as patients, and were invited to complete
      two surveys evaluating perceptions of the program. The program consisted of
      weekly patient interactions during which students were required to assess and
      treat a "patient" under strict simulation guidelines and in accordance with
      stated learning objectives. Items rated included self-perceived skills,
      confidence, time management, and clinical placement readiness and included
      collection of qualitative responses. Surveys were released at commencement and
      completion of the simulation program. RESULTS: Of 79 third-year students, 63%
      completed survey 1 and 66% completed survey 2. Students had high expectations of
      the program and these were consistently met. Peer simulation rated highly for all
      items, including identifying knowledge and skill deficits, and improving
      confidence, clinical reasoning, time management, and communication. Simulation
      was considered safe, supportive, engaging, and valuable for clinical placement
      preparation. Students identified some lack of authenticity when working with
      peers. CONCLUSIONS: Peer simulation was perceived by students as valuable in
      preparing them for clinical placement, despite a perceived lack of realism. These
      findings support the use of peer simulation as an alternative to the use of more
      formalized standardized patients in an undergraduate physiotherapy program.
      Further investigation is required to establish a detailed cost analysis of the
      program and to determine the amount of realism required to optimize the benefits
      of this promising educational strategy.

PMID- 29346227
TI  - Refractory Pain Management in Amyloid-Associated Peripheral Neuropathy.
AB  - OBJECTIVE: Systemic amyloidosis is a disease that often involves multiple organ
      systems, including the peripheral nervous system. Patients may present with
      severe, refractory neuropathic pain; however, the optimal treatment approach for
      pain for these patients remains unclear. CASE REPORT: A man with severe,
      refractory neuropathic pain in his bilateral upper and lower extremities and the
      trunk secondary to amyloid neuropathy is presented. Multiple medication trials,
      including neuropathic and opioid agents, produced considerable adverse effects
      and minimal relief. Scrambler therapy, a novel electrical stimulation modality,
      was used and was associated with substantial short-term but nonsustained benefit.
      Spinal cord stimulation was considered, but given his diffuse symptoms, it was
      deemed a less-than-optimal approach. Ultimately, an intrathecal drug delivery
      system was placed with infusion of hydromorphone, resulting in substantial pain
      reduction in all involved areas and with an improved adverse effect profile. This
      intervention resulted in immense improvement in the patient's quality of life,
      despite progression of his systemic amyloidosis. CONCLUSIONS: Severe pain in the
      setting of amyloid neuropathy is often difficult to treat. To our knowledge, this
      represents the first report of Scrambler therapy or an implanted intrathecal drug
      delivery system used for a patient with refractory amyloidosis-related
      neuropathic pain, resulting in substantial analgesic benefit and improved quality
      of life.

PMID- 29346228
TI  - Analgesia of Combined Femoral Triangle and Obturator Nerve Blockade Is Superior
      to Local Infiltration Analgesia After Total Knee Arthroplasty With High-Dose
      Intravenous Dexamethasone.
AB  - BACKGROUND AND OBJECTIVES: High-dose intravenous dexamethasone reduces the
      postoperative opioid requirement and is often included in the multimodal
      analgesia strategy after total knee arthroplasty (TKA). Combined obturator nerve
      and femoral triangle blockade (OFB) reduces the opioid consumption and pain after
      TKA better than local infiltration analgesia (LIA). The question is whether
      preoperative high-dose intravenous dexamethasone would cancel out the superior
      analgesic effect of OFB compared with LIA. The aim was to evaluate the analgesic
      effect of OFB versus LIA after TKA when all patients received high-dose
      intravenous dexamethasone. METHODS: Eighty-two patients were randomly assigned
      either to OFB or LIA after primary unilateral TKA. All patients received 16 mg
      dexamethasone. Primary outcome was morphine consumption via patient-controlled
      analgesia during the first 20 postoperative hours. Secondary outcomes were pain,
      nausea, dizziness, and length of hospital stay. RESULTS: Seventy-four patients
      were included in the analysis. Median total intravenous morphine consumption
      during the first 20 postoperative hours was 6 mg (interquartile range [IQR], 2-18
      mg) in the OFB group and 20 mg (IQR, 12-28 mg) in the LIA group. The 14-mg
      difference (95% confidence interval, 6.4-18.0 mg) was significant (P < 0.001).
      There was no difference in pain score at rest at 20 hours postoperatively: 2
      (IQR, 1-4) in the OFB group and 3 (IQR, 2-5) in the LIA group. CONCLUSIONS:
      Combined OFB reduces morphine consumption better than LIA after TKA even when all
      patients received high-dose intravenous dexamethasone. CLINICAL TRIAL
      REGISTRATION: This study was registered at ClinicalTrials.gov, identifier
      NCT02374008.

PMID- 29346229
TI  - Anatomical Variations of the Vertebral Artery in the Upper Cervical Spine:
      Clinical Relevance for Procedures Targeting the C1/C2 and C2/C3 Joints.
AB  - BACKGROUND AND OBJECTIVES: Accidental breach of the vertebral artery (VA) during
      the performance of cervical pain blocks can result in significant morbidity.
      Whereas anatomical variations have been described for the foraminal (V2) segment
      of the VA, those involving its V3 portion (between the C2 transverse process and
      dura) have not been investigated and may be of importance for procedures
      targeting the third occipital nerve or the lateral atlantoaxial joint. METHODS:
      Five hundred computed tomography angiograms of the neck performed in patients
      older than 50 years for the management of cerebrovascular accident or cervical
      trauma (between January 2010 and May 2016) were retrospectively and independently
      reviewed by 2 neuroradiologists. Courses of the VA in relation to the lateral
      aspect of the C2/C3 joint and the posterior surface of the C1/C2 joint were
      examined. For the latter, any medial encroachment of the VA (or one of its
      branches) was noted. The presence of a VA loop between C1 and C2 and its distance
      from the upper border of the superior articular process (SAP) of C3 were also
      recorded. If the VA loop coursed posteriorly, its position in relation to 6
      fields found on the lateral aspects of the articular pillars of C2 and C3 was
      tabulated. RESULTS: At the C1/C2 level, the VA coursed medially over the lateral
      quarter of the dorsal joint surface in 1% of subjects (0.6% and 0.4% on the left
      and right sides, respectively; P = 0.998). A VA loop originating between C1 and
      C2 was found to travel posteroinferiorly over the anterolateral aspect of the
      inferior articular pillar of C2 in 55.5% of patients on the left and 41.9% on the
      right side (P < 0.001), as well as over the SAP of C3 in 0.4% of subjects. When
      present in the quadrant immediately cephalad to the C3 SAP, VA loops coursed
      within 2.0 +/- 1.5 and 3.3 +/- 2.5 mm on the left and right sides, respectively,
      of its superior aspect (P < 0.001). CONCLUSIONS: The VA commonly travels adjacent
      to areas targeted by third occipital nerve procedures and more rarely over the
      access point for lateral atlantoaxial joint injections. Modifications to existing
      techniques may reduce the risk of accidental VA breach.

PMID- 29346230
TI  - Chronic Hematoma of the Neck.
AB  - Chronic hematomas are defined as hematomas with slow, progressive growth over
      many weeks. They are an extremely rare cause of acute neck swelling in the
      pediatric population. They consist of an organized central mass of blood with
      granulation tissue and fibrotic changes peripherally. The presence of a capsule
      prevents resorption but allows for intracapsular bleeding with subsequent
      expansion. We describe a case of a 6-year-old girl who presented to the emergency
      department with a spontaneously occurring left neck mass in the supraclavicular
      region. A possible neoplasm was suggested on imaging. The patient was referred to
      a head and neck surgeon, she underwent a thorough workup, and the mass was
      ultimately surgically excised. Histologically, the mass was confirmed to be a
      chronic hematoma. The patient recovered uneventfully, and there has been no
      recurrence.

PMID- 29346231
TI  - The Complex Association of Race/Ethnicity With Pain Treatment Quality in an Urban
      Medical Center With 2 Pediatric Emergency Departments.
AB  - OBJECTIVE: This study aimed to explore racial differences in analgesia quality.
      METHODS: A retrospective cross-sectional study of 24,733 visits by individuals 21
      years or younger with pain scores of 4 to 10 was performed using electronic
      medical records. We compared 2 process metrics, treatment with any analgesics
      within 60 minutes and treatment with opioids within 60 minutes, and one outcome
      metric, a reduction in pain score by 2 or more points within 90 minutes.
      Multivariable logistic regression adjusted for the effects of patient
      characteristics and health status. We also determined variations in analgesia
      quality among those with severe pain. RESULTS: When compared with white children,
      black children were more likely to receive any analgesia (adjusted odds ratio
      [aOR], 1.94; 95% confidence interval, 1.71-2.21), but both blacks (aOR, 0.66;
      0.51-0.85) and Hispanics (aOR, 0.56; 0.39-0.80) were less likely to receive
      opioids. Blacks were more likely to reduce their pain score (aOR, 1.50; 1.28
      1.76).Among children with severe pain, both blacks and Hispanics were more likely
      to receive any analgesia (black: aOR, 2.05 [1.71-2.46]; Hispanic: aOR, 1.29 [1.05
      1.59]), and Hispanic children were less likely to receive opioids (aOR, 0.58;
      0.37-0.91). Again, black children were more likely to reduce their pain score
      (aOR, 1.42; 1.13-1.79). CONCLUSIONS: The relationship between race/ethnicity and
      analgesia is complex. Although minority children were less likely to receive
      opioids, black children had better treatment outcomes. Future studies should
      explore clinical response to analgesia in addition to process measures to better
      understand if differential treatment may be justified to achieve equitable care
      outcomes.

PMID- 29346232
TI  - Use of Point-of-Care Ultrasound to Guide Pediatric Gastrostomy Tube Replacement
      in the Emergency Department.
AB  - The presentation of a pediatric patient to the emergency department for a
      malfunctioning or dislodged gastrostomy tube (G-tube) is not uncommon. As such,
      these tubes are often replaced at the bedside. Improper placement can result in a
      number of complications, including perforation, fistula tract formation,
      peritonitis, and sepsis. The current criterion standard method to confirm proper
      G-tube placement is contrast-enhanced radiography. However, point-of-care
      ultrasound may be an alternative method to guide and confirm pediatric G-tube
      replacement in the emergency department. We report a series of cases on this
      novel point-of-care ultrasound application.

PMID- 29346233
TI  - Video Recordings to Analyze Preventable Management Errors in Pediatric
      Resuscitation Bay.
AB  - OBJECTIVE: In treating patients of different ages and diseases in the pediatric
      resuscitation bay, management errors are common. This study aimed to analyze the
      adherence to advanced trauma life support and pediatric advanced life support
      guidelines and identify management errors in the pediatric resuscitation bay by
      using video recordings. METHODS: Video recording of all patients admitted to the
      pediatric resuscitation bay at University Children's Hospital Zurich during a 13
      month period was performed. Treatment adherence to advanced trauma life support
      guidelines and pediatric advanced life support guidelines and errors per patient
      were identified. RESULTS: During the study period, 128 patients were recorded
      (65.6% with surgical, 34.4% with medical diseases). The most common causes for
      admission were traumatic brain injury (21.1%), multiple trauma (20.3%), and
      seizures (14.8%). There was a statistically significant correlation between
      accurate handover from emergency medical service to hospital physicians and
      adherence to airway, breathing, circulation, and disability sequence (correlation
      coefficient [CC], 0.205; P = 0.021), existence of a defined team leader and
      adherence to airway, breathing, circulation, and disability sequence (CC, 0.856;
      P < 0.001), and accurate hand over and existence of a defined team leader (CC,
      0.186; P = 0.037). Unexpected errors were revealed. Cervical spine
      examination/stabilization was omitted in 40% of admitted surgical patients, even
      in 20% of patients with an injury of spine/limbs. CONCLUSIONS: Video recording is
      a useful tool to evaluate patient management in the pediatric resuscitation bay.
      Analyzing errors of missing the adherence to the guidelines helps to pay
      attention and focus on specific items to improve patient care.

PMID- 29346234
TI  - A Qualitative Study of Multidisciplinary Providers' Experiences With the Transfer
      Process for Injured Children and Ideas for Improvement.
AB  - OBJECTIVE: Most injured children initially present to a community hospital, and
      many will require transfer to a regional pediatric trauma center. The purpose of
      this study was 1) to explore multidisciplinary providers' experiences with the
      process of transferring injured children and 2) to describe proposed ideas for
      process improvement. METHODS: This qualitative study involved 26 semistructured
      interviews. Subjects were recruited from 6 community hospital emergency
      departments and the trauma and transport teams of a level I pediatric trauma
      center in New Haven, Conn. Participants (n = 34) included interprofessional
      providers from sending facilities, transport teams, and receiving facilities.
      Using the constant comparative method, a multidisciplinary team coded transcripts
      and collectively refined codes to generate recurrent themes across interviews
      until theoretical saturation was achieved. RESULTS: Participants reported that
      the transfer process for injured children is complex, stressful, and necessitates
      collaboration. The transfer process was perceived to involve numerous
      interrelated components, including professions, disciplines, and institutions.
      The 5 themes identified as areas to improve this transfer process included 1)
      Creation of a unified standard operating procedure that crosses
      institutions/teams, 2) Enhancing 'shared sense making' of all providers, 3)
      Improving provider confidence, expertise, and skills in caring for pediatric
      trauma transfer cases, 4) Addressing organization and environmental factors that
      may impede/delay transfer, and 5) Fostering institutional and personal
      relationships. CONCLUSIONS: Efforts to improve the transfer process for injured
      children should be guided by the experiences of and input from multidisciplinary
      frontline emergency providers.

PMID- 29346236
TI  - A Teenager With Acute Anterograde Amnesia.
AB  - Isolated amnesia is an uncommon presenting complaint in the pediatric age group.
      We report the case of an 18-year-old woman who presented with the acute onset of
      memory difficulty and an otherwise normal neurologic examination. Brain magnetic
      resonance imaging demonstrated inflammation in the bilateral temporal lobes.
      Serum and cerebrospinal fluid testing ultimately revealed a diagnosis of
      autoimmune encephalitis. Although rare, the acute onset of isolated amnesia
      deserves a prompt, comprehensive evaluation.

PMID- 29346235
TI  - Posttraumatic Stress in Children After Injury: The Role of Acute Pain and Opioid
      Medication Use.
AB  - OBJECTIVES: After injury, many children experience posttraumatic stress symptoms
      (PTSS) that negatively impact recovery. Acute pain and PTSS share neurobiological
      pathways, and acute dosage of morphine has been linked to reduced PTSS in
      naturalistic studies. However, the complex interactions between pain, morphine
      and other opioid use, and PTSS have yet to be investigated in robust pediatric
      samples.This prospective, longitudinal study examined relationships between acute
      pain, opioid medications, and PTSS after pediatric injury. METHODS: Ninety-six
      children aged 8 to 13 years (mean = 10.60, SD = 1.71), hospitalized for
      unintentional injury, completed assessments at baseline (T1) and 12 weeks (T2)
      later. Pain ratings and opioid administration data were obtained via chart
      review. RESULTS: Structural equation modeling revealed that worst pain endorsed
      during hospitalization was positively associated with concurrent and later PTSS
      when controlling for evidence-based risk factors (ie, age, sex, prior trauma
      history, traumatic appraisals of injury event, heart rate). Neither opioid
      medications overall nor morphine specifically (milligram/kilogram/day)
      administered during hospitalization mediated the relationship between pain and T2
      PTSS. CONCLUSIONS: Pain during hospitalization may increase susceptibility for
      persistent PTSS above and beyond the influence of other empirical risk factors.
      Findings suggest that pain assessment may be a useful addition to pediatric PTSS
      screening tools and highlight the need for additional research on pharmacological
      secondary prevention approaches. Given that inadequate pain control and
      persistent PTSS each hinder recovery and long-term functioning, better
      understanding of interactions between acute pain and PTSS after injury is
      essential for improving screening, prevention, and early intervention efforts.

PMID- 29346237
TI  - Pediatric Pelvic Fractures and Differences Compared With the Adult Population.
AB  - INTRODUCTION: Although pelvic fractures in children are rare, because of
      anatomical differences between an adult's skeleton and a child's skeleton, these
      lesions in the pediatric population have specific characteristics that need to be
      borne in mind when dealing with them. MATERIALS AND METHODS: A retrospective
      chart review was performed on the pelvic fractures in skeletally immature
      patients treated in our hospital in the last 20 years. RESULTS: Eighty-one pelvic
      fractures in children were treated between 1993 and 2013. The mean age was 9.98
      years, with 61.7%(50/81) boys and 38.2% (31/81) girls. A traffic accident was the
      main injury mechanism (74%, 60/81), and height fall was in second place (16%,
      13/81). Following Tile pelvic fracture classification, type A2 was the most
      frequent (58.04%, 47/81); and following Torode and Zieg classification, type IIIA
      (45.68%, 37/81).Associated injuries were present in 77.8% (63/81) of the
      patients; fractures of other bones and head trauma were the most frequent. An
      acetabular fracture was present in 13.5% (11/81) of the patients.Nonsurgical
      treatment was chosen for all the pelvic fractures except in 4 patients, which
      required surgical management for their pelvic injuries. Blood transfusion was
      required in 32% (26/81) of the patients, and arterial embolization was not needed
      in any case. Furthermore, 11.1% (9/81) required a stay in the pediatric care
      unit, and the death rate was 8.64% (7/81).The mean length of hospital stay was
      12.4 days. CONCLUSIONS: Because of the specific characteristics of pelvic
      fractures in children, fracture patterns are less severe than those of adults,
      but the injury mechanisms are high-energy traumas. The rate of associated
      injuries is very high, and a multidisciplinary management in pediatric trauma
      centers is needed to treat these patients.

PMID- 29346238
TI  - Trends in Severe Pediatric Emergency Conditions in a National Cohort, 2008 to
      2014.
AB  - OBJECTIVE: The objective of this study was to determine the incidence and recent
      trends in serious pediatric emergency conditions. METHODS: We conducted a cross
      sectional study of the Nationwide Emergency Department Sample from 2008 through
      2014, and included patients with age below 18 years with a serious condition,
      defined as each diagnosis group in the diagnosis grouping system with a severity
      classification system score of 5. We calculated national incidences for each
      serious condition using annualized weighted condition counts divided by annual
      United States census child population counts. We determined the highest-incidence
      serious conditions over the study period and calculated percentage changes
      between 2008 and 2014 for each serious condition using a Poisson model. RESULTS:
      The 2008 incidence of serious conditions across the national child population was
      1721 visits per million person-years (95% confidence interval, 1485-1957). This
      incidence increased to 2020 visits per million person-years (95% confidence
      interval, 1661-2379) in 2014. The most common serious conditions were serious
      respiratory diseases, septicemia, and serious neurologic diseases. Anaphylaxis
      was the condition with the largest change, increasing by 147%, from 101 to 249
      visits per million person-years. CONCLUSIONS: The most common serious condition
      in children presenting to United States emergency departments is serious
      respiratory disease. Anaphylaxis is the fastest increasing serious condition.
      Additional research attention to these diagnoses is warranted.

PMID- 29346239
TI  - FACTORS ASSOCIATED WITH DEVELOPMENT OF DISSOCIATED OPTIC NERVE FIBER LAYER
      APPEARANCE IN THE PIONEER INTRAOPERATIVE OPTICAL COHERENCE TOMOGRAPHY STUDY.
AB  - PURPOSE: To assess the relationship of dissociated optic nerve fiber layer
      (DONFL) and intraoperative membrane-peeling dynamics as visualized using
      intraoperative optical coherence tomography (OCT), and to evaluate the functional
      implications of DONFL. METHODS: This was a post hoc analysis of eyes undergoing
      membrane peeling for vitreomacular interface disorders in the prospective PIONEER
      intraoperative OCT study. Retinal layer measurements in preincision and postpeel
      intraoperative OCT images were obtained. The primary outcome was development of
      DONFL appearance on spectral domain OCT at 6-month follow-up. Secondary outcomes
      included correlation of DONFL with surgical technique, surgical indication,
      intraoperative OCT findings, and retinal sensitivity. RESULTS: Ninety-five eyes
      were included. The prevalence of DONFL at 6 months was 36%. Increased inner
      retinal layer thickness on intraoperative OCT immediately after membrane peeling
      was associated with development of DONFL (P < 0.01). Macular hole repair was
      significantly associated with DONFL appearance. Peel technique (forceps vs.
      diamond-dusted membrane scraper) was not associated with DONFL. There was no
      difference in retinal sensitivity or visual acuity between eyes with or without
      DONFL. CONCLUSION: Acute postpeel increase in inner retinal thickness and macular
      hole repair were associated with development of DONFL appearance. However, it is
      unclear whether the surgical indication (e.g., macular hole) or the surgical
      manipulations performed (e.g., internal limiting membrane peeling) is the major
      factor that has an impact on DONFL appearance. Overall, these findings suggest
      that one mechanism in the development of DONFL appearance may be intraoperative
      trauma to the inner retina, potentially during internal limiting membrane peeling
      (e.g., macular hole repair).

PMID- 29346240
TI  - RESPONSE OF INFLAMMATORY CYSTOID MACULAR EDEMA TO TREATMENT USING ORAL
      ACETAZOLAMIDE.
AB  - PURPOSE: To determine the treatment effect of oral acetazolamide on refractory
      inflammatory macular edema. METHODS: A retrospective review of identified
      patients with uveitic or pseudophakic macular edema treated using acetazolamide
      between 2007 and 2014. Visual acuity and central macular subfield thickness was
      determined at baseline and at first follow-up. Baseline optical coherence
      tomography features were analyzed as predictors of acetazolamide response.
      RESULTS: Sixteen patients (19 eyes) of 61 screened met all criteria. Mean age was
      57.9 years (19.7-81.1). The most common diagnosis was idiopathic uveitis (n = 6,
      31.6%). Mean uveitis duration was 4.4 years (0.2-27.5). Average central macular
      subfield thickness decreased significantly (from 471.8 +/- 110.6 MUm to 358.3 +/-
      50.4 MUm) (P < 0.0001). Average visual acuity (logarithm of the minimum angle of
      resolution) improved significantly from 20/54 (0.43 +/- 0.25) to 20/37 (0.27 +/-
      0.16) (P = 0.003). Pretreatment optical coherence tomographies demonstrated
      intraretinal fluid (n = 19, 100%), subretinal fluid (n = 8, 42.1%), epiretinal
      membrane (n = 13, 68.3%), and vitreomacular traction (n = 1, 5.2%). No optical
      coherence tomography characteristic was predictive of a response to therapy.
      CONCLUSION: There is a significant benefit to vision and central macular subfield
      thickness after acetazolamide treatment in patients with inflammatory macular
      edema. In patients with refractory inflammatory macular edema, treatment using
      acetazolamide can provide anatomical and visual benefit without corticosteroid
      related adverse effects.

PMID- 29346241
TI  - CHRONIC CENTRAL SEROUS CHORIORETINOPATHY: Early and Late Morphological and
      Functional Changes After Verteporfin Photodynamic Therapy.
AB  - PURPOSE: To describe early and late morphological and functional changes in
      subjects receiving photodynamic therapy (PDT) for chronic central serous
      chorioretinopathy. METHODS: Patients with chronic central serous
      chorioretinopathy were prospectively enrolled and received standard PDT. At the
      baseline examination, each subject underwent complete ophthalmological
      examination, including best-corrected visual acuity (BCVA) assessment,
      fluorescein angiography and indocyanine green angiography, spectral domain
      optical coherence tomography, and microperimetry. Spectral domain optical
      coherence tomography, microperimetry, and BCVA assessment were repeated in
      multiple sections over 7 days after PDT and at 1-, 3-, and 12-month intervals.
      Main outcome measures were: identification of early changes (1-week examination)
      in BCVA, retinal sensitivity, and spectral domain optical coherence tomography
      parameters and their influence on outcomes at the 1-year follow-up. RESULTS:
      Three main patterns of early response to PDT were identified during the 1-week
      examination. The neurosensory retinal detachment most frequently decreased
      rapidly (12/19 pts), with complete resolution in 50% of cases. An increase in
      neurosensory retinal detachment height was registered in 16% (3/19) of cases,
      whereas in 21% (4/19), a large fluctuation in neurosensory retinal detachment was
      encountered. Best-corrected visual acuity declined significantly in 5/12 patients
      in the first group and was stable or improved in the remaining cases. Overall,
      retinal sensitivity diminished in 16/19 subjects, with a mean worsening of 2.56
      dB (P = 0.0002). At the 12-month examination, final mean BCVA improved by 14.4
      letters (P = 0.001) and a similar progressive recovery in the retinal sensitivity
      was observed (+2.69 dB, P = 0.0039). The neurosensory retinal detachment
      completely resolved in 18/19 (95%) cases, with a parallel significant reduction
      in central foveal choroidal thickness (P < 0.0001). CONCLUSION: Three patterns of
      early response to standard PDT can be identified. Although an early and abrupt
      reduction in BCVA and retinal sensitivity after treatment is possible, this does
      not compromise a final improvement in visual functions.

PMID- 29346242
TI  - PREVALENCE AND CLINICAL CHARACTERISTICS OF PACHYDRUSEN IN POLYPOIDAL CHOROIDAL
      VASCULOPATHY: Multimodal Image Study.
AB  - PURPOSE: To investigate the prevalence of a newly defined drusen type,
      pachydrusen, soft drusen, and subretinal drusenoid deposits in eyes with
      polypoidal choroidal vasculopathy and fellow eyes and the relationship between
      each drusen type and the choroidal thickness, vascular morphology, and
      hyperpermeability. METHODS: The 169 eyes of 90 patients with polypoidal choroidal
      vasculopathy were retrospectively reviewed. The prevalence of each drusen type
      was evaluated using color fundus photography and optical coherence tomography.
      The choroidal thickness and presence of pachyvessels on optical coherence
      tomography and choroidal vascular hyperpermeability on indocyanine green
      angiography were compared among the drusen groups. RESULTS: Pachydrusen, soft
      drusen, and subretinal drusenoid deposits were found in 49.3%, 12.3%, and 6.9% in
      polypoidal choroidal vasculopathy eyes. The mean subfoveal choroidal thickness of
      the pachydrusen, soft drusen, and subretinal drusenoid deposit groups was 403.1,
      184.4, and 176.4 um. The pachydrusen group showed significantly thicker choroid
      than the others. The choroidal hyperpermeability was noticed at 41.7%, 0%, and 0%
      and the pachyvessel was observed at 80.6%, 44.4%, and 40% in pachydrusen, soft
      drusen, and subretinal drusenoid deposit groups, respectively. CONCLUSION: In
      patients with polypoidal choroidal vasculopathy, pachydrusen was prevalent and
      associated with thicker choroid. Polypoidal choroidal vasculopathy with
      pachydrusen was highly associated with choroidal vascular hyperpremeability and
      pachyvessel morphology than other types of drusen.

PMID- 29346243
TI  - PARS PLANA VITRECTOMY WITH ANTERIOR CHAMBER VERSUS GORE-TEX SUTURED POSTERIOR
      CHAMBER INTRAOCULAR LENS PLACEMENT: LONG-TERM OUTCOMES.
AB  - PURPOSE: To compare clinical outcomes of combined pars plana vitrectomy (PPV)
      with anterior chamber intraocular lens (ACIOL) placement versus scleral fixation
      of a posterior chamber intraocular lens (PCIOL) using Gore-Tex suture. METHODS:
      Retrospective, interventional case series of eyes undergoing combined PPV and IOL
      placement for retained lens material, aphakia, or dislocated IOL. Eyes with
      history of amblyopia, corneal opacity, retinal, or optic nerve disease were
      excluded. Outcome measures were change in visual acuity and occurrence of
      postoperative complications with minimum follow-up of 1 year. RESULTS: Sixty
      three eyes of 60 patients were identified. Thirty-three eyes underwent combined
      PPV and ACIOL placement and 30 eyes underwent combined PPV and scleral fixation
      of a PCIOL using Gore-Tex suture. Mean follow-up was 502 +/- 165 days (median
      450, range 365-1,095 days). In the ACIOL group, mean visual acuity improved from
      20/914 preoperatively to 20/50 postoperatively (P < 0.001). In the scleral
      fixated PCIOL group, mean visual acuity improved from 20/677 preoperatively to
      20/46 postoperatively (P < 0.001). No difference in visual acuity was noted
      between groups at 1-year (P = 0.91) or final follow-up (P = 0.62). Regarding
      postoperative complications, eyes undergoing ACIOL placement had a significantly
      higher rate of transient corneal edema (30.3 vs. 6.7%, P = 0.02) compared with
      eyes undergoing scleral fixation of a PCIOL. CONCLUSION: Combined PPV with ACIOL
      placement or scleral fixation of a PCIOL with Gore-Tex suture were well
      tolerated. The techniques resulted in similar visual outcomes at minimum follow
      up of 1 year.

PMID- 29346244
TI  - COMPARING FUNDUS FLUORESCEIN ANGIOGRAPHY AND SWEPT-SOURCE OPTICAL COHERENCE
      TOMOGRAPHY ANGIOGRAPHY IN THE EVALUATION OF DIABETIC MACULAR PERFUSION.
AB  - PURPOSE: To compare fundus fluorescein angiography (FFA) and swept-source optical
      coherence tomography angiography (SS-OCTA) in the evaluation of macular perfusion
      in diabetic patients. METHODS: Forty-one eyes (21 diabetic patients) seen at
      Moorfields Eye Hospital (London) over a 1-month interval underwent color fundus
      photography, FFA, and SS-OCTA imaging of the capillary superficial plexus using 2
      different protocols: 3 * 3 mm and 4.5 * 4.5 mm. Quantitative assessment (foveal
      avascular zone diameters and area), qualitative analysis (macroscopic and
      microscopic levels) and Early Treatment Diabetic Retinopathy Study diabetic
      macular ischemia grading were performed. Artifacts were recorded. Intraclass
      correlation coefficients and weighted kappa values were calculated. RESULTS: Mean
      (SD) foveal avascular zone area was 0.695 (0.52) mm on FFA, 0.627 (0.54) mm on SS
      OCTA 3 * 3 and 0.701 (0.54) mm on SS-OCTA 4.5 * 4.5 protocol. Intraclass
      correlation coefficients showed good agreement between FFA and SS-OCTA for both
      vertical diameter and foveal avascular zone area measurements. The agreement
      between SS-OCTA 3 * 3 and 4.5 * 4.5 was good for all quantitative measurements.
      Weighted kappa for diabetic macular ischemia grading showed low to fair agreement
      between FFA and SS-OCTA, whereas the agreement was good between two different SS
      OCTA protocols. CONCLUSION: Swept-source OCTA is a reproducible technique in the
      assessment of macular perfusion in diabetic patients with special regards to
      foveal avascular zone analysis. The agreement with FFA is limited especially for
      diabetic macular ischemia grading. Fundus fluorescein angiography is more
      sensitive in identifying microaneurysms.

PMID- 29346245
TI  - Diagnostic Yield and Safety of Bronchoscopist-directed Moderate Sedation With a
      Bolus Dose Administration of Propofol During Endobronchial Ultrasound
      Bronchoscopy.
AB  - BACKGROUND: The propofol use for moderate sedation (MS) during endobronchial
      ultrasound (EBUS) bronchoscopy is primarily restricted for use by an
      anesthesiologist because of safety concerns. The goals of this study were to
      demonstrate the safety and the diagnostic yield of the use of propofol by
      bronchoscopists and trained endoscopy nurses during EBUS bronchoscopy without
      intubation. METHODS: We tested a bolus propofol administration protocol targeting
      MS for EBUS bronchoscopy. A fixed initial dose of 40 mg of propofol along with a
      fixed 50 mcg fentanyl dose were administered. Sedation assessment was performed
      every 2 minutes, and repeated bolus doses of propofol were given to maintain MS
      under the direction of the bronchoscopist. RESULTS: A total of 122 subjects
      underwent EBUS bronchoscopy with a goal of MS from August 2015 to April 2017. In
      total, 110 subjects who underwent convex EBUS bronchoscopy under MS with propofol
      were included in the analysis. Median procedure duration was 57 minutes (range,
      15 to 97 min). Deep sedation and agitation-related delay were occurred in 14 and
      21 subjects, respectively. Hemodynamic instability and hypoxemia occurred in 23
      subjects. However, there was no need for vasopressors or artificial airway
      placement. Median of total propofol dose per case was 560 mg. Diagnostic yield
      for malignancy and granuloma was 68%, and a median of 4 lymph node stations were
      sampled per subject. All specimens with adenocarcinoma were sufficient for
      genetic marker analysis. There were no major sedation-related complications.
      CONCLUSION: A bolus administration of propofol during EBUS bronchoscopy provided
      excellent adequacy of sedation and well tolerance safety profile.

PMID- 29346246
TI  - Comparison of Diagnostic Potential of Narrow Band Imaging Bronchoscopy Over White
      Light Bronchoscopy in Lung Cancer.
AB  - BACKGROUND: Worldwide, lung cancer is the largest contributor to new cancer
      diagnoses and to death from cancer. Narrow band imaging (NBI) is a novel
      bronchoscopic technique which enables detailed examination of submucosal
      microcapillary grid and showed great potential in early detection of malignant
      lesions of the bronchial mucosa. The aim of this study was to compare diagnostic
      potential of NBI bronchoscopy over white light (WL) bronchoscopy in lung cancer.
      METHODS: We enrolled 187 patients having clinical and radiologic findings highly
      suspicious of lung cancer. Patients were further divided into 2 groups: NBI group
      (n=102), and control WL group (n=85). Bronchoscopy examination was performed with
      respective visualization modes and all pathologic lesions were biopsied and
      histologically confirmed. RESULTS: On NBI bronchoscopy, malignancy was suspected
      in 69 patients, of whom 62 had malignancy, and 33 patients were suspected of
      inflammation, of whom 32 had inflammation and only 1 patient had malignancy.
      Under WL bronchoscopy, 54 patients were suspected of malignancy, of whom 36 had
      malignancy, and 31 patients were suspected of inflammation, of whom 23 had
      inflammatory disease and 8 had malignancy. NBI bronchoscopy had sensitivity
      98.1%, specificity 82.05%, positive predictive value 89.86% and negative
      predictive value 96.97% in comparison to standard WL bronchoscopy which had
      sensitivity 81.82%, specificity 56.10%, positive predictive value 66.67% and
      negative predictive value 74.19%. CONCLUSION: NBI bronchoscopy demonstrated
      better results in comparison to WL bronchoscopy. The presence of pathologic
      vascularization of the tumor helps to better identify the malignant process.
      Inflammatory changes in the mucosa can be easily differentiated from malignant
      changes by the appearance of vessels.

PMID- 29346247
TI  - Concurrent Versus Sequential Intrapleural Instillation of Tissue Plasminogen
      Activator and Deoxyribonuclease for Pleural Infection.
AB  - BACKGROUND: Treatment of pleural infection with instillation of sequential
      intrapleural tissue plasminogen activator (tPA) and human recombinant
      deoxyribonuclease (DNase) twice daily for a total of 6 doses has been shown to
      decrease surgical referral and improve radiographic imaging. This labor-intensive
      regimen was empirically chosen. Thus, it remains unclear whether the 2 drugs can
      be administered immediately one after the other (concurrent administration)
      instead of instilling them separately with a 1-hour to 2-hour interval in between
      (sequential administration). The aim of this study was to compare the efficacy
      and safety of sequential versus concurrent tPA/DNase therapy in patients with
      pleural infection. METHODS: This was a prospective observational study.
      Consecutive patients with pleural infection who received concurrent and
      sequential tPA/DNase were included. The initiation and number of doses of
      tPA/DNase therapy were based on the amount of pleural fluid drainage, clinical
      response and radiographic findings. RESULTS: A total of 38 patients with pleural
      infection received tPA/DNase treatment: 18 in the sequential group and 20 in the
      concurrent group. Treatment was successful in 77.7% in the sequential group and
      75% in concurrent group (P=0.57). There was no statistically significant
      difference between the 2 treatment groups (sequential and concurrent) in median
      pleural fluid drainage (P=0.45), median volume of pleural effusion estimated on
      chest computed tomography scan (P=0.4) or median hemithorax occupied by effusion
      on chest radiography (P=0.83) following intrapleural therapy. One patient
      required a blood transfusion for gradual pleural blood loss in each treatment
      group. Pain needing escalation of analgesia affected 3 patients in each arm but
      none required cessation of therapy. CONCLUSION: A simpler regimen of concurrent
      administration of intrapleural tPA/DNase as compared with sequential intrapleural
      therapy is safe, effective, and represents a viable option for the management of
      pleural infection.

PMID- 29346248
TI  - The Utility of Ultrasound to Diagnose Tunnel-Tract Infection Related to
      Indwelling Pleural Catheters.
AB  - Indwelling pleural catheter (IPC) infections lead to increased morbidity and
      treatment failure in patients with chronic recurrent pleural effusions.
      Ultrasonography is a readily available diagnostic tool used by pulmonologists on
      a daily basis. Ultrasonography has been used to identify the etiology of
      indwelling peritoneal catheter obstruction, including infection of the exit site
      and tunnel tract. The use of ultrasonography to identify tunnel-tract infection
      involving IPC has not been reported. We describe the ultrasonographic
      characteristics of 3 cases of confirmed tunnel-tract infection and compared them
      with noninfected chronic IPCs. Ultrasonographic evaluation of the soft tissue
      tunnel tract can accurately identify fluid collections around the catheter and
      cuff, which is highly suggestive of tunnel-tract infection.

PMID- 29346249
TI  - 1% Versus 2% Lignocaine for Airway Anesthesia in Flexible Bronchoscopy Without
      Lignocaine Nebulization (LIFE): A Randomized Controlled Trial.
AB  - BACKGROUND: The ideal concentration of lignocaine for topical anesthesia in
      bronchoscopy remains investigational. In this randomized, double blind study, we
      compared 1% versus 2% lignocaine for topical anesthesia. METHODS: Consecutive
      patients undergoing bronchoscopy were randomized to receive either 1% or 2%
      lignocaine solution by spray-as-you-go technique. All received 10% lignocaine
      spray to the oropharynx along with nasal 2% lignocaine gel. Nebulized lignocaine
      was not administered. Primary outcomes were operator-rated overall procedural
      satisfaction, visual analogue scale (VAS)-rated and operator-rated cough, VAS.
      Secondary objectives were total lignocaine dose administered, patient-rated pain
      on faces pain scale, cumulative dose of lignocaine and procedural complications.
      RESULTS: A total of 500 patients (250 in each group) were randomized. Baseline
      characteristics were comparable. Operator-rated overall procedural satisfaction,
      VAS (72.05+/-20.16 and 72.20+/-21.96 in 1% and 2% group respectively; P=0.93) and
      operator-rated cough, VAS [1% group: 19.1 (12.6-34.6) and 2% group: 20.6 (12.5
      36.9); P>0.05] were similar between the 2 groups. Cumulative dose of lignocaine
      used in 2% lignocaine group was greater (220.89+/-12.96 mg in 1% and 319.55+/
      19.32 mg in 2% group; P<0.001). Patients receiving sedation were comparable
      between the 2 groups. (10% in 1% lignocaine group and 6% in 2% lignocaine group;
      P=0.13). Minor complications occurred in 2 patients in each group. CONCLUSION:
      One percent lignocaine in flexible bronchoscopy is as efficacious as 2%
      lignocaine when administered using the spray as you go technique without
      concurrent lignocaine nebulization, at a significantly lower total dose of
      lignocaine administered.

PMID- 29346250
TI  - Incidence, Etiology, and Clinicopathologic Features of Endobronchial Benign
      Lesions: A 10-Year Consecutive Retrospective Study.
AB  - BACKGROUND: Airways can be affected by non-neoplastic lesions leading to critical
      stenosis of the lumen. Incidence, etiology, and clinical significance of
      endobronchial benign lesions are not systematically characterized.This study
      aimed to assess the epidemiology of nonmalignant processes involving the
      bronchial tree on clinical, pathologic, endoscopic, and radiologic grounds.
      METHODS: We retrospectively analyzed bronchoscopy procedures over 10 years at the
      Bronchoscopy Unit of Modena University Hospital. All the endoscopically growing
      benign lesions with histologic confirmation were considered. For each lesion, we
      evaluated demographics, clinical features and outcome, the endoscopic aspect and
      radiologic characteristics by means of computed tomography as assessed by 2
      experienced radiologists blinded with regard to the diagnosis. RESULTS: Over the
      study period, we analyzed 10,431 bronchoscopies and identified 2075 cases of
      tracheobronchial alterations. Among these, 11.2% had a benign etiology with an
      average annual incidence of 23 new cases/year and a general incidence of 2.2%.
      Anthrachosis was the most prevalent bronchial lesion. In total, 22% of benign
      lesions presented airway stenosis >50% and required bronchoscopic treatment.
      Bronchial stenosis was most frequently observed in tuberculosis (P=0.031) and
      aspergillosis (P=0.020) when compared with sarcoidosis. Immunosuppressive status
      was significantly associated with endobronchial aspergillosis (P=0.0001) and the
      1-year survival from diagnosis resulted significantly lower irrespectively to the
      immune system condition. CONCLUSIONS: A consistent proportion of endobronchial
      benign lesions are reported. One fifth of these are associated with critical
      stenosis of the airway lumen, requiring rigid bronchoscopy. Among these,
      aspergillosis is characterized by the poorest prognosis, regardless of host
      immunity status.

PMID- 29346251
TI  - Combined Endosonography Reduces Time to Diagnose Pulmonary Coccidioidomycosis.
AB  - Coccidioidomycosis causes significant morbidity in endemic areas. In the absence
      of sensitive diagnostic serologic testing, clinicians have increasingly relied on
      lung and lymph node biopsies for diagnosis. Recently, endobronchial ultrasound
      guided transbronchial needle aspiration (EBUS-TBNA) has been shown to be an
      excellent sampling method for the diagnosis and staging of lung cancers,
      especially when combined with endoscopic ultrasound guided fine needle aspiration
      (EUS-FNA). We present 13 consecutive cases where EBUS-TBNA and/or EUS-FNA of
      pulmonary lymph nodes were performed as part of the workup for pulmonary
      coccidioidomycosis. EBUS-TBNA+EUS-FNA led to diagnosis in all nine cases in which
      they were performed concurrently, and in the remaining 4 in which either was
      performed individually. BAL was performed in all cases with positive results in 5
      (38%). The mean time to diagnose by EBUS/EUS (1.6 d) was significantly shorter
      than by bronchoalveolar lavage (6.3 d) (P=0.003). The findings indicate that
      combined EBUS-TBNA+EUS-FNA for lymph node biopsy facilitates early and accurate
      diagnosis of pulmonary coccidioidomycosis.

PMID- 29346252
TI  - Sarcoidosis With Pleural Effusion as the Presenting Symptom.
AB  - A 65-year-old woman, never smoker, with medical history of hypertension,
      nonischemic cardiomyopathy, and moderate pulmonary hypertension presented with
      symptomatic bilateral pleural effusions. Thoracentesis revealed a lymphocyte
      predominant transudate and was negative for malignancy, microbiologic cultures
      were negative for an infectious cause. Chest tomography showed mediastinal and
      bilateral hilar lymphadenopathy, lymph node biopsy with endobronchial ultrasound
      guided transbronchial needle aspiration showed non-necrotizing granulomas
      compatible with sarcoidosis. Echocardiogram showed ejection fraction of 45% and
      cardiac workup for sarcoid involvement was negative. Despite overall clinical
      management with diuretics, pleural effusion persisted and the patient underwent
      medical thoracoscopy with pleural biopsy. Biopsy showed noncaseating granulomas
      consistent with sarcoid, with all stains and microbiologic cultures negative for
      an infectious etiology. To the best of our knowledge, this is the first described
      case of sarcoidosis presenting as large transudative pleural effusion.

PMID- 29346253
TI  - An Innovative Solution for Prolonged Air Leaks: The Customized Endobronchial
      Silicone Blocker.
AB  - BACKGROUND: Prolonged air leak (PAL) is a life-threatening condition that can
      present either as bronchopleural fistula, or alveolar-pleural fistula (APF).
      Although numerous bronchoscopic treatments are described, they are either
      expensive, not widely available in the developing world or have limited success.
      We describe our experience with a novel customized endobronchial silicone blocker
      (CESB) for PAL treatment. METHODS: This is a retrospective study of PAL patients
      who underwent CESB placement. The air leak was localized using a balloon
      occlusion test. The CESB was uniquely designed by molding silicone stent pieces
      into a conical shape, deployed with rigid bronchoscopy into the appropriate
      segment, and reinforced with cyanoacrylate glue to prevent migration. In patients
      with APF, pleurodesis was performed after leak resolution to prevent recurrence.
      Following this, the CESB was removed after 6 weeks. RESULTS: Forty-nine CESBs
      were placed in 31 patients (25 male individuals, 6 female individuals) with mean
      age of 49.7+/-19.7 years. The PALs included APF (n=16), bronchopleural fistula
      (n=14), and airway-mediastinal fistula (n=1). The average diameter of the CESB
      used was 7.9+/-2.9 mm. There was resolution of the PAL in 26 of 31 patients
      (84%). The CESB migrated in 5 patients with no adverse events. Pleurodesis was
      performed in 13 of 16 patients with APF, to prevent recurrence. No other
      significant complications were observed. CONCLUSIONS: CESBs represent a safe,
      effective, and innovative approach in the management of PAL. They should be
      considered in patients who are not surgical candidates, fail surgery, or those
      who have a recurrence following surgery.

PMID- 29346254
TI  - Long-term Outcomes of Pediatric En Bloc Compared to Living Donor Kidney
      Transplantation: A Single-Center Experience With 25 Years Follow-Up.
AB  - BACKGROUND: Pediatric en bloc kidneys are considered marginal for transplantation
      into adults. We aimed to compare the long-term outcomes of pediatric en bloc
      versus living donor kidney transplantation. METHODS: A retrospective review was
      undertaken on pediatric en bloc and living donor kidney transplants performed at
      our center between 1990 and 2001. The outcomes compared between the groups
      included 25 year graft survival and longitudinal glomerular filtration rate.
      RESULTS: There were 72 pediatric en bloc and 75 living donor kidney recipients
      included in the analysis. Pediatric donors were 16.9 +/- 11.2 months old and
      weighed 10.7 +/- 3.8 kg with terminal serum creatinine of 0.50 +/- 0.45 mg/dL.
      Living donors were 40.1 +/- 9.4 years old and serum creatinine was 0.90 +/- 0.16
      mg/dL at the time of donation. En bloc kidney recipients had higher dialysis
      vintage (23.0 +/- 29.2 months vs 14.3 +/- 14.7 months; P = 0.03), and longer cold
      ischemia time (30.5 +/- 9.8 hours vs 2.6 +/- 0.9 hours, P < 0.001). Kaplan-Meier
      estimate revealed similar graft survival between the groups up to 27 years of
      follow up (log rank P = 0.78). Estimated glomerular filtration rate was
      significantly higher in pediatric en bloc kidney recipients from years 5 through
      17 posttransplantation. CONCLUSIONS: Pediatric en bloc kidneys conferred long
      term graft survival similar to living donor kidneys over a 25-year period after
      transplantation along with superior graft function. These findings support
      improved utilization of pediatric kidneys for transplantation into adults which
      not only helps to alleviate organ shortage but also provide excellent long-term
      function.

PMID- 29346255
TI  - Safety of BCG Vaccination in Pediatric Liver Transplant Recipients.

PMID- 29346256
TI  - Causes, Preventability, and Cost of Unplanned Rehospitalizations Within 30 Days
      of Discharge After Lung Transplantation.
AB  - BACKGROUND: Unplanned rehospitalizations (UR) within 30 days of discharge are
      common after lung transplantation. It is unknown whether UR represents
      preventable gaps in care or necessary interventions for complex patients. The
      objective of this study was to assess the incidence, causes, risk factors, and
      preventability of UR after initial discharge after lung transplantation. METHODS:
      This was a single-center prospective cohort study. Subjects completed a modified
      short physical performance battery to assess frailty at listing and at initial
      hospital discharge after transplantation and the State-Trait Anxiety Inventory at
      discharge. For each UR, a study staff member and the patient's admitting or
      attending clinician used an ordinal scale (0, not; 1, possibly; 2, definitely
      preventable) to rate readmission preventability. A total sum score of 2 or higher
      defined a preventable UR. RESULTS: Of the 90 enrolled patients, 30 (33.3%) had an
      UR. The single most common reasons were infection (7 [23.3%]) and atrial
      tachyarrhythmia (5 [16.7%]). Among the 30 URs, 9 (30.0%) were deemed preventable.
      Unplanned rehospitalization that happened before day 30 were more likely to be
      considered preventable than those between days 30 and 90 (30.0% versus 6.2%, P =
      0.04). Discharge frailty, defined as short physical performance battery less than
      6, was the only variable associated with UR on multivariable analysis (odds
      ratio, 3.4; 95% confidence interval, 1.1-11.8; P = 0.04). CONCLUSIONS: Although
      clinicians do not rate the majority of UR after lung transplant as preventable,
      discharge frailty is associated with UR. Further research should identify whether
      modification of discharge frailty can reduce UR.

PMID- 29346258
TI  - Quantifying Frailty in Post-Lung Transplant Patients-Can We Predict Who Will Need
      Readmission?

PMID- 29346257
TI  - Association of Cold Ischemia Time With Acute Renal Transplant Rejection.
AB  - BACKGROUND: Kidney transplantation holds much promise as a treatment of choice
      for patients with end-stage kidney disease. The impact of cold ischemia time
      (CIT) on acute renal transplant rejection (ARTR) remains to be fully studied in a
      large cohort of renal transplant patients. METHODS: From the Organ Procurement
      and Transplantation Network database, we analyzed 63 798 deceased donor renal
      transplants performed between 2000 and 2010. We assessed the association between
      CIT and ARTR. We also evaluated the association between recipient age and ARTR.
      RESULTS: Six thousand eight hundred two (11%) patients were clinically diagnosed
      with ARTR. Longer CIT was associated with an increased risk of ARTR. After
      multivariable adjustment, compared with recipients with CIT < 12 hours, the
      relative risk of ARTR was 1.13 (95% confidence interval, 1.04-1.23) in recipients
      with CIT >= 24 hours. The association of CIT and ARTR was more pronounced in
      patients undergoing retransplantation: compared with recipients with CIT less
      than 12 hours, the relative risk of ARTR was 1.66 (95% confidence interval, 1.01
      2.73) in recipients with CIT of 24 hours or longer. Additionally, older age was
      associated with a decreased risk of ARTR. Compared with recipients aged 18 to 29
      years, the relative risk of ARTR was 0.50 (95% confidence interval, 0.45-0.57) in
      recipients 60 years or older. Longer CIT was also associated with increased risk
      of death-censored graft loss. Compared with recipients with CIT less than 12
      hours, the hazard ratio of death-censored graft loss was 1.22 (95% confidence
      interval, 1.14-1.30) in recipients with CIT of 24 hours or longer. CONCLUSIONS:
      Prolonged CIT is associated with an increased risk of ARTR and death-censored
      graft loss. Older age was associated with a lower risk of ARTR.

PMID- 29346259
TI  - Do Patients Supported With Continuous-flow Left Ventricular Assist Device Have a
      Sufficient Risk of Death to Justify a Priority Allocation? A Propensity Score
      Matched Analysis of Patients Listed in UNOS Status 2.
AB  - BACKGROUND: Outcomes of continuous flow left ventricular assist devices (CF
      LVADs) as bridge to transplant have significantly improved. The question has
      arisen whether patients on CF-LVADs have an increased risk of death on the
      waiting list as to justify a priority allocation (status 1). The aim of this
      study was to compare the survival after implantation of CF-LVADs with the
      survival on the waiting list for patients initially listed in United Network for
      Organ Sharing (UNOS) status 2. METHODS: All patients 18 years or older listed for
      heart transplantation (HT) in the United States between 2011 and 2013 in UNOS
      status 2 with no mechanical circulatory support at time of listing were analyzed.
      Patients were divided into 2 groups, depending on whether they received a new CF
      LVAD while listed (CF-LVAD group) or not (NO-LVAD) and were further matched on
      their propensity score (PS) in a 1:2 ratio. RESULTS: Two hundred eighty-seven CF
      LVAD patients were matched to 574 NO-LVAD patients. Survival after CF-LVAD was
      significantly lower at 24 months compared with waiting list (75.4 +/- 4.4% vs
      91.2 +/- 8.9%, P < 0.0001). Further, survival was not significantly different
      between the 2 groups at 24 months after transplantation (81.3 +/- 5.9% vs 86.7 +/
      3.3%, P = 0.3). CONCLUSIONS: Survival of patients listed in UNOS status 2 who
      receive a CF-LVAD while listed is significantly lower compared to patients who do
      not receive mechanical support on the waiting list. The current priority in the
      allocation system given to patients on CF-LVAD seems justified. Further
      posttransplant survival is not negatively influenced by previous CF-LVAD
      implantation.

PMID- 29346260
TI  - Race, Risk, and Willingness of End-Stage Renal Disease Patients Without Hepatitis
      C Virus to Accept an HCV-Infected Kidney Transplant.
AB  - BACKGROUND: Despite effective antiviral treatment, hundreds of kidneys from
      deceased donors with hepatitis C virus (HCV) are discarded annually. Little is
      known about the determinants of willingness to accept HCV-infected kidneys among
      HCV-negative patients. METHODS: At 2 centers, 189 patients undergoing initial or
      reevaluation for transplant made 12 hypothetical decisions about accepting HCV
      infected kidneys in which we systematically varied expected HCV cure rate,
      allograft quality, and wait time for an uninfected kidney. RESULTS: Only 29% of
      the participants would accept an HCV-infected kidney under all scenarios, whereas
      53% accepted some offers and rejected others, and 18% rejected all HCV-infected
      kidneys. Higher cure rate (odds ratio [OR], 3.49; 95% confidence interval [CI],
      2.33-5.24 for 95% vs 75% probability of HCV cure), younger donor (OR, 2.34; 95%
      CI, 1.91-2.88 for a 20-year-old vs a 60-year-old hypertensive donor), and longer
      wait for an uninfected kidney (OR, 1.43; 95% CI, 1.22-1.67 for 5 years vs 2
      years) were associated with greater willingness to accept an HCV-infected kidney.
      Black race modified the effect of HCV cure rate, such that willingness to accept
      a kidney increased less for blacks versus whites as the cure rate improved.
      Patients older than 60 years and prior kidney recipients showed greater
      willingness to accept an HCV-infected organ. CONCLUSIONS: Most patients will
      consider an HCV-infected kidney in some situations. Future trials using HCV
      infected kidneys may enhance enrollment by targeting older patients and prior
      transplant recipients, but centers should anticipate that black patients'
      acceptance of HCV-infected kidneys will be reduced compared with white patients.

PMID- 29346261
TI  - The Authors' Reply.

PMID- 29346262
TI  - Important Facts About Organ Donation and OPO Performance.

PMID- 29346263
TI  - Clinical Application of Real-Time Shear Wave Elastography in Identifying the
      Histological Components of Parotid Adenolymphoma.
AB  - OBJECTIVE: This study aimed to investigate the relationship between the elastic
      modulus and the histological components of parotid adenolymphoma by using real
      time shear wave elastography. METHODS: A total of 157 patients, histologically
      confirmed as having parotid adenolymphoma, were enrolled in the study. The
      maximum and the mean elastic modulus of the parotid mass were measured by using
      preoperative shear wave elastography. Parotid adenolymphoma was
      histopathologically subdivided into different types based on the relative
      proportion of stromal to cellular components. RESULTS: The maximal elasticity of
      parotid adenolymphoma ranged from 20.67 to 160.90 kPa, and the mean elasticity
      was 83.18 +/- 39.15 kPa. The maximal elasticity of the 3 types of parotid
      adenolymphoma was 34.21 to 155.20, 20.67 to 104.20, and 45.89 to 160.90 kPa,
      respectively. The mean elasticity of the 3 types of parotid adenolymphoma was
      89.16 +/- 40.62, 63.24 +/- 28.07, and 111.10 +/- 37.85 kPa, respectively. The
      difference in the maximal elasticity among 3 groups was significant (P < 0.01).
      There was no significant difference in maximal elasticity of type II and type III
      as compared with type I adenolymphoma (P > 0.05). The maximal elasticity of type
      III adenolymphoma was significantly higher than that of type II (P < 0.05, t =
      3.12). CONCLUSION: Shear wave elastography depicts parotid adenolymphoma with a
      variable appearance because of the relative proportions of stromal to cellular
      contents in the mass.

PMID- 29346264
TI  - Sonography of the Cecum: Gateway to the Right Lower Quadrant.
AB  - Sonography of the cecum has come of age largely as a consequence of the
      successful evolution of appendiceal sonography as a useful tool in the evaluation
      of patients with right lower-quadrant pain. At some medical centers, graded
      compression sonography (GCS) has become the initial imaging study of choice in
      the assessment of these individuals. The cecum serves as a helpful anatomic
      landmark for localization of the appendix in these examinations-providing a
      sonographic starting point in the search for the appendix. During GCS, primary
      pathology within the cecum itself can become evident, including a variety of
      processes, such as infectious, inflammatory, or neoplastic disorders, whose
      presentations commonly mimic that of appendicitis. The accurate diagnosis of
      cecal abnormalities and their differentiation from acute appendicitis play
      valuable roles in the management of affected patients because the options for
      further workup and subsequent treatment vary greatly according to the diagnosis
      at hand. Additionally, the compressed cecum often becomes an acoustic window into
      the right lower quadrant, revealing pathology apart from the appendix within the
      right iliac fossa. The purpose of this pictorial essay is to highlight the
      importance and value of performing a careful evaluation of the cecum during GCS
      of patients with suspected appendicitis and to review the differential diagnosis
      and imaging findings of primary cecal abnormalities whose clinical presentations
      can mimic that of acute appendicitis.

PMID- 29346267
TI  - Erratum: Lavergne, S.N. In Vitro Research Tools in the Field of Human Immediate
      Drug Hypersensitivity and Their Present Use in Small Animal Veterinary Medicine
      Vet. Sci. 2017, 4, 1.
AB  - Due to an error during production, the author, Lavergne S. Lavergne's name in the
      published paper [1] was incorrect.[...].

PMID- 29346266
TI  - The Relationship between Autism Spectrum Disorder and Melatonin during Fetal
      Development.
AB  - The aim of this review is to clarify the interrelationship between melatonin and
      autism spectrum disorder (ASD) during fetal development. ASD refers to a diverse
      range of neurodevelopmental disorders characterized by social deficits, impaired
      communication, and stereotyped or repetitive behaviors. Melatonin, which is
      secreted by the pineal gland, has well-established neuroprotective and circadian
      entraining effects. During pregnancy, the hormone crosses the placenta into the
      fetal circulation and transmits photoperiodic information to the fetus allowing
      the establishment of normal sleep patterns and circadian rhythms that are
      essential for normal neurodevelopment. Melatonin synthesis is frequently impaired
      in patients with ASD. The hormone reduces oxidative stress, which is harmful to
      the central nervous system. Therefore, the neuroprotective and circadian
      entraining roles of melatonin may reduce the risk of neurodevelopmental disorders
      such as ASD.

PMID- 29346265
TI  - Halfway between 2D and Animal Models: Are 3D Cultures the Ideal Tool to Study
      Cancer-Microenvironment Interactions?
AB  - An area that has come to be of tremendous interest in tumor research in the last
      decade is the role of the microenvironment in the biology of neoplastic diseases.
      The tumor microenvironment (TME) comprises various cells that are collectively
      important for normal tissue homeostasis as well as tumor progression or
      regression. Seminal studies have demonstrated the role of the dialogue between
      cancer cells (at many sites) and the cellular component of the microenvironment
      in tumor progression, metastasis, and resistance to treatment. Using an
      appropriate system of microenvironment and tumor culture is the first step
      towards a better understanding of the complex interaction between cancer cells
      and their surroundings. Three-dimensional (3D) models have been widely described
      recently. However, while it is claimed that they can bridge the gap between in
      vitro and in vivo, it is sometimes hard to decipher their advantage or limitation
      compared to classical two-dimensional (2D) cultures, especially given the broad
      number of techniques used. We present here a comprehensive review of the
      different 3D methods developed recently, and, secondly, we discuss the pros and
      cons of 3D culture compared to 2D when studying interactions between cancer cells
      and their microenvironment.

PMID- 29346268
TI  - Effect of Novel Quercetin Titanium Dioxide-Decorated Multi-Walled Carbon
      Nanotubes Nanocomposite on Bacillus subtilis Biofilm Development.
AB  - The present work was targeted to design a surface against cell seeding and
      adhering of bacteria, Bacillus subtilis. A multi-walled carbon nanotube/titanium
      dioxide nano-power was produced via simple mixing of carbon nanotube and titanium
      dioxide nanoparticles during the sol-gel process followed by heat treatment.
      Successfully, quercetin was immobilized on the nanocomposite via physical
      adsorption to form a quercetin/multi-walled carbon nanotube/titanium dioxide
      nanocomposite. The adhesion of bacteria on the coated-slides was verified after
      24 h using confocal laser-scanning microscopy. Results indicated that the
      quercetin/multi-walled carbon nanotube/titanium dioxide nanocomposite had more
      negativity and higher recovery by glass surfaces than its counterpart. Moreover,
      coating surfaces with the quercetin-modified nanocomposite lowered both
      hydrophilicity and surface-attached bacteria compared to surfaces coated with the
      multi-walled carbon nanotubes/titanium dioxide nanocomposite.

PMID- 29346270
TI  - Resistance to HIV Integrase Inhibitors: About R263K and E157Q Mutations.
AB  - The use of integrase inhibitors (INI) is increasing in antiretroviral therapies
      (ART) and INI are not all equal regarding genetic barrier to resistance. The aim
      of this manuscript was to review main in vivo and in vitro knowledge about two
      particular integrase resistance-associated mutations: R263K and E157Q. The R263K
      mutation was the first mutation rarely found selected at time of virological
      failure in patients failing a first-line dolutegravir-based treatment. Further in
      vitro studies on R263K mutants showed a moderate increase in phenotypic
      resistance level and a drastic reduction in viral replicative capacity. No
      compensatory mutations were evidenced. The E157Q mutation is polymorphic, found
      between 1.7% and 5.6% of viral sequences issued from ART-naive patients depending
      on the viral subtype; as well as acquired resistance emerging at failure of a
      raltegravir-based regimen in two case reports. We reported data on phenotypic
      resistance level of E157Q mutants and virological response of patients harboring
      a E157Q virus initiating an INI-based regimen, showing that dolutegravir might be
      the most recommended INI in such patients. These findings show that there is
      still a need for a better understanding of resistance mechanisms to INI and
      emphasized the importance of genotypic background in viral evolution under drug
      pressure.

PMID- 29346271
TI  - "Bacterial Toxins" Section in the Journal Toxins: A Fantastic Multidisciplinary
      Interplay between Bacterial Pathogenicity Mechanisms, Physiological Processes,
      Genomic Evolution, and Subsequent Development of Identification Methods,
      Efficient Treatment, and Prevention of Toxigenic Bacteria.
AB  - Toxins are powerful pathogenicity factors produced by certain bacteria, fungi,
      animals, and plants which mediate drastic interactions of these pathogens on the
      organism host[...].

PMID- 29346269
TI  - Identification of Secreted Proteins Involved in Nonspecific dsRNA-Mediated
      Lutzomyia longipalpis LL5 Cell Antiviral Response.
AB  - Hematophagous insects transmit infectious diseases. Sand flies are vectors of
      leishmaniasis, but can also transmit viruses. We have been studying immune
      responses of Lutzomyia longipalpis, the main vector of visceral leishmaniasis in
      the Americas. We identified a non-specific antiviral response in L. longipalpis
      LL5 embryonic cells when treated with non-specific double-stranded RNAs (dsRNAs).
      This response is reminiscent of interferon response in mammals. We are
      investigating putative effectors for this antiviral response. Secreted molecules
      have been implicated in immune responses, including interferon-related responses.
      We conducted a mass spectrometry analysis of conditioned medium from LL5 cells 24
      and 48 h after dsRNA or mock treatment. We identified 304 proteins. At 24 h, 19
      proteins had an abundance equal or greater than 2-fold change, while the levels
      of 17 proteins were reduced when compared to control cells. At the 48 h time
      point, these numbers were 33 and 71, respectively. The two most abundant secreted
      peptides at 24 h in the dsRNA-transfected group were phospholipid scramblase, an
      interferon-inducible protein that mediates antiviral activity, and forskolin
      binding protein (FKBP), a member of the immunophilin family, which mediates the
      effect of immunosuppressive drugs. The transcription profile of most candidates
      did not follow the pattern of secreted protein abundance.

PMID- 29346272
TI  - Viral and Antibody Kinetics, and Mosquito Infectivity of an Imported Case of Zika
      Fever Due to Asian Genotype (American Strain) in Singapore.
AB  - We report a case of a Singaporean who acquired Zika virus (ZIKV) during a visit
      to Cuba. The infection was confirmed using molecular and serological methods.
      This report highlights potential drawbacks of using IgG serology for diagnosis of
      flavivirus infections in endemic regions. The low viremia detected during the
      early phase of this case resulted in low mosquito infectivity rates, suggesting
      the possibility of ZIKV transmission prior to clinical onset. The report also
      emphasizes the challenges of public health interventions for Zika fever and the
      importance of sustaining a low vector population to reduce the risk of arbovirus
      transmission in vulnerable regions.

PMID- 29346273
TI  - Report on the Symposium "Molecular Mechanisms Involved in Neurodegeneration".
AB  - The prevalence of neurodegenerative diseases is currently a major concern in
      public health because of the lack of neuroprotective and neuroregenerative drugs.
      The symposium on Molecular Mechanisms Involved in Neurodegeneration held in
      Varadero, Cuba, updated the participants on the basic mechanisms of
      neurodegeneration, on the different approaches for drug discovery, and on early
      research results on therapeutic approaches for the treatment of neurodegenerative
      diseases. Alzheimer's disease and in silico research were covered by many of the
      presentations in the symposium, under the umbrella of the "State of the Art of
      Non-clinical Models for Neurodegenerative Diseases" International Congress, held
      from 20 to 24 June 2017. This paper summarizes the highlights of the symposium.

PMID- 29346274
TI  - IRF4 Mediates the Oncogenic Effects of STAT3 in Anaplastic Large Cell Lymphomas.
AB  - Systemic anaplastic large cell lymphomas (ALCL) are a category of T-cell non
      Hodgkin's lymphomas which can be divided into anaplastic lymphoma kinase (ALK)
      positive and ALK negative subgroups, based on ALK gene rearrangements. Among
      several pathways aberrantly activated in ALCL, the constitutive activation of
      signal transducer and activator of transcription 3 (STAT3) is shared by all ALK
      positive ALCL and has been detected in a subgroup of ALK negative ALCL. To
      discover essential mediators of STAT3 oncogenic activity that may represent
      feasible targets for ALCL therapies, we combined gene expression profiling
      analysis and RNA interference functional approaches. A shRNA screening of STAT3
      modulated genes identified interferon regulatory factor 4 (IRF4) as a key driver
      of ALCL cell survival. Accordingly, ectopic IRF4 expression partially rescued
      STAT3 knock-down effects. Treatment with immunomodulatory drugs (IMiDs) induced
      IRF4 down regulation and resulted in cell death, a phenotype rescued by IRF4
      overexpression. However, the majority of ALCL cell lines were poorly responsive
      to IMiDs treatment. Combination with JQ1, a bromodomain and extra-terminal (BET)
      family antagonist known to inhibit MYC and IRF4, increased sensitivity to IMiDs.
      Overall, these results show that IRF4 is involved in STAT3-oncogenic signaling
      and its inhibition provides alternative avenues for the design of
      novel/combination therapies of ALCL.

PMID- 29346276
TI  - Comparison of the Response of Male BALB/c and C57BL/6 Mice in Behavioral Tasks to
      Evaluate Cognitive Function.
AB  - To evaluate several cognitive parameters during the execution of behavioral tasks
      assessing cognitive function in laboratory animals, the parameters are reported
      within a range. This situation entails that each laboratory must establish the
      conditions under which the behavioral task to evaluate the cognitive function can
      be carried out. C57BL/6 and BALB/c inbred strains are used more often in
      behavioral studies relating to anxiety, stress, fear and cognitive function. The
      aim of this work was to compare the behavioral response of mice of the strains
      BALB/c and C57BL/6 to evaluate memory and learning as cognitive functions. Young
      male mice, 7-8 weeks of age, from each strain were used. Y maze, object
      recognition and passive avoidance tasks were performed. Both strains of mice
      showed differences in the response to the passive avoidance and Y maze task. This
      study advances knowledge about the baseline behavior of laboratory mice strains
      and their response during the experimental procedures, which are due to the
      treatment, genetic influence, procedural differences, genetic background
      variance, or any combination of these elements.

PMID- 29346275
TI  - A Review on Recent Advances in Stabilizing Peptides/Proteins upon Fabrication in
      Hydrogels from Biodegradable Polymers.
AB  - Hydrogels evolved as an outstanding carrier material for local and controlled
      drug delivery that tend to overcome the shortcomings of old conventional dosage
      forms for small drugs (NSAIDS) and large peptides and proteins. The aqueous
      swellable and crosslinked polymeric network structure of hydrogels is composed of
      various natural, synthetic and semisynthetic biodegradable polymers. Hydrogels
      have remarkable properties of functionality, reversibility, sterilizability, and
      biocompatibility. All these dynamic properties of hydrogels have increased the
      interest in their use as a carrier for peptides and proteins to be released
      slowly in a sustained manner. Peptide and proteins are remarkable therapeutic
      agents in today's world that allow the treatment of severe, chronic and life
      threatening diseases, such as diabetes, rheumatoid arthritis, hepatitis. Despite
      few limitations, hydrogels provide fine tuning of proteins and peptides delivery
      with enormous impact in clinical medicine. Novels drug delivery systems composed
      of smart peptides and molecules have the ability to drive self-assembly and form
      hydrogels at physiological pH. These hydrogels are significantly important for
      biological and medical fields. The primary objective of this article is to review
      current issues concerned with the therapeutic peptides and proteins and impact of
      remarkable properties of hydrogels on these therapeutic agents. Different routes
      for pharmaceutical peptides and proteins and superiority over other drugs
      candidates are presented. Recent advances based on various approaches like self
      assembly of peptides and small molecules to form novel hydrogels are also
      discussed. The article will also review the literature concerning the
      classification of hydrogels on a different basis, polymers used, "release
      mechanisms" their physical and chemical characteristics and diverse applications.

PMID- 29346278
TI  - A Case Study in Citizen Science: The Effectiveness of a Trap-Neuter-Return
      Program in a Chicago Neighborhood.
AB  - The use of trap-neuter-return (TNR) as a method of managing free-roaming cat
      populations has increased in the United States in recent decades. Historically,
      TNR has been conducted most often at a grassroots level, which has led to
      inconsistent data collection and assessment practices. Consequently, a paucity of
      analyzable data exists. An initiative is underway to standardize TNR program data
      collection and assessment. However, it could be some time before scientifically
      sound protocols are implemented on a broad scale. In the interim, sets of data
      collected by nascent citizen scientists offer valid opportunities to evaluate
      grassroots TNR programs. The purpose of the present study was to examine the
      effectiveness of a TNR program conducted by a citizen scientist located in
      Chicago, Illinois, where a county law permitting TNR was enacted in 2007. Colony
      populations, when grouped by the number of years enrolled in the program,
      declined by a mean of 54% from entry and 82% from peak levels. Results from
      coexistent TNR programs in the Chicago area are consistent with these findings.

PMID- 29346277
TI  - Vaccinia Virus in Blood Samples of Humans, Domestic and Wild Mammals in Brazil.
AB  - Outbreaks of Vaccinia virus (VACV) affecting cattle and humans have been reported
      in Brazil in the last 15 years, but the origin of outbreaks remains unknown.
      Although VACV DNA have been already detected in mice (Mus musculus), opossums
      (Didelphis albiventris) and dogs during VACV zoonotic outbreaks, no transmission
      to cattle or humans from any of these were reported during Brazilian outbreaks.
      In this work, we assessed the PCR positivity to VACV in blood samples of cows and
      other domestic mammals, wild rodents and other wild mammals, and humans from
      areas with or without VACV infection reports. Our results show the detection of
      VACV DNA in blood samples of cows, horse and opossums, raising important
      questions about VACV spread.

PMID- 29346279
TI  - How Neighborhood Effects Vary: Childbearing and Fathering among Latino and
      African American Adolescents.
AB  - This study examines what neighborhood conditions experienced at age 15 and after
      are associated with teen childbearing and fathering among Latino and African
      American youth and whether these neighborhood effects vary by gender and/or
      ethnicity. Administrative and survey data from a natural experiment are used for
      a sample of 517 Latino and African American youth whose families were quasi
      randomly assigned to public housing operated by the Denver (CO) Housing Authority
      (DHA). Characteristics of the neighborhood initially assigned by DHA to wait list
      applicants are utilized as identifying instruments for the neighborhood contexts
      experienced during adolescence. Cox Proportional Hazards (PH) models reveal that
      neighborhoods having higher percentages of foreign-born residents but lower
      levels of social capital robustly predict reduced odds of teen parenting though
      the magnitude of these effects was contingent on gender and ethnicity.
      Specifically, the presence of foreign-born neighbors on the risk of teen
      parenting produced a stronger dampening effect for African American youth when
      compared to Latino youth. Additionally, the effects of social capital on teen
      parenting were stronger for males than females.

PMID- 29346280
TI  - A Multi-Band Body-Worn Distributed Radio-Frequency Exposure Meter: Design, On
      Body Calibration and Study of Body Morphology.
AB  - A multi-band Body-Worn Distributed exposure Meter (BWDM) calibrated for
      simultaneous measurement of the incident power density in 11 telecommunication
      frequency bands, is proposed. The BDWM consists of 22 textile antennas integrated
      in a garment and is calibrated on six human subjects in an anechoic chamber to
      assess its measurement uncertainty in terms of 68% confidence interval of the on
      body antenna aperture. It is shown that by using multiple antennas in each
      frequency band, the uncertainty of the BWDM is 22 dB improved with respect to
      single nodes on the front and back of the torso and variations are decreased to
      maximum 8.8 dB. Moreover, deploying single antennas for different body
      morphologies results in a variation up to 9.3 dB, which is reduced to 3.6 dB
      using multiple antennas for six subjects with various body mass index values. The
      designed BWDM, has an improved uncertainty of up to 9.6 dB in comparison to
      commercially available personal exposure meters calibrated on body. As an
      application, an average incident power density in the range of 26.7-90.8 MUW.m -
      2 is measured in Ghent, Belgium. The measurements show that commercial personal
      exposure meters underestimate the actual exposure by a factor of up to 20.6.

PMID- 29346281
TI  - A Prototype Sensor for In Situ Sensing of Fine Particulate Matter and Volatile
      Organic Compounds.
AB  - Air pollution exposure causes seven million deaths per year, according to the
      World Health Organization. Possessing knowledge of air quality and sources of air
      pollution is crucial for managing air pollution and providing early warning so
      that a swift counteractive response can be carried out. An optical prototype
      sensor (AtmOptic) capable of scattering and absorbance measurements has been
      developed to target in situ sensing of fine particulate matter (PM2.5) and
      volatile organic compounds (VOCs). For particulate matter testing, a test chamber
      was constructed and the emission of PM2.5 from incense burning inside the chamber
      was measured using the AtmOptic. The weight of PM2.5 particles was collected and
      measured with a filter to determine their concentration and the sensor signal-to
      concentration correlation. The results of the AtmOptic were also compared and
      found to trend well with the Dylos DC 1100 Pro air quality monitor. The
      absorbance spectrum of VOCs emitted from various laboratory chemicals and
      household products as well as a two chemical mixtures were recorded. The
      quantification was demonstrated, using toluene as an example, by calibrating the
      AtmOptic with compressed gas standards containing VOCs at different
      concentrations. The results demonstrated the sensor capabilities in measuring
      PM2.5 and volatile organic compounds.

PMID- 29346282
TI  - Smartphone-Based Cooperative Indoor Localization with RFID Technology.
AB  - In GPS-denied indoor environments, localization and tracking of people can be
      achieved with a mobile device such as a smartphone by processing the received
      signal strength (RSS) of RF signals emitted from known location beacons (anchor
      nodes), combined with Pedestrian Dead Reckoning (PDR) estimates of the user
      motion. An enhacement of this localization technique is feasible if the users
      themselves carry additional RF emitters (mobile nodes), and the cooperative
      position estimates of a group of persons incorporate the RSS measurements
      exchanged between users. We propose a centralized cooperative particle filter
      (PF) formulation over the joint state of all users that permits to process RSS
      measurements from both anchor and mobile emitters, as well as PDR motion
      estimates and map information (if available) to increase the overall positioning
      accuracy, particularly in regions with low density of anchor nodes. Smartphones
      are used as a convenient mobile platform for sensor measurements acquisition, low
      level processing, and data transmission to a central unit, where cooperative
      localization processing takes place. The cooperative method is experimentally
      demonstrated with four users moving in an area of 1600 m 2 , with 7 anchor nodes
      comprised of active RFID (radio frequency identification) tags, and additional
      mobile tags carried by each user. Due to the limited coverage provided by the
      anchor beacons, RSS-based individual localization is inaccurate (6.1 m median
      error), but this improves to 4.9 m median error with the cooperative PF. Further
      gains are produced if the PDR information is added to the filter: median error of
      3.1 m (individual) and 2.6 m (cooperative); and if map information is also
      considered, the results are 1.8 m (individual) and 1.6 m (cooperative). Thus, for
      each version of the particle filter, cooperative localization outperforms
      individual localization in terms of positioning accuracy.

PMID- 29346283
TI  - The Biological Role of Hyaluronan-Rich Oocyte-Cumulus Extracellular Matrix in
      Female Reproduction.
AB  - Fertilization of the mammalian oocyte requires interactions between spermatozoa
      and expanded cumulus extracellular matrix (ECM) that surrounds the oocyte. This
      review focuses on key molecules that play an important role in the formation of
      the cumulus ECM, generated by the oocyte-cumulus complex. In particular, the
      specific inhibitors (AG1478, lapatinib, indomethacin and MG132) and progesterone
      receptor antagonist (RU486) exerting their effects through the remodeling of the
      ECM of the cumulus cells surrounding the oocyte have been described. After
      gonadotropin stimulus, cumulus cells expand and form hyaluronan (HA)-rich cumulus
      ECM. In pigs, the proper structure of the cumulus ECM depends on the interaction
      between HA and serum-derived proteins of the inter-alpha-trypsin inhibitor
      (IalphaI) protein family. We have demonstrated the synthesis of HA by cumulus
      cells, and the presence of the IalphaI, tumor necrosis factor-alpha-induced
      protein 6 and pentraxin 3 in expanding oocyte-cumulus complexes (OCC). We have
      evaluated the covalent linkage of heavy chains of IalphaI proteins to HA, as the
      principal component of the expanded HA-rich cumulus ECM, in porcine OCC cultured
      in medium with specific inhibitors: AG1478 and lapatinib (both inhibitors of
      epidermal growth factor receptor tyrosine kinase activity); MG132 (a specific
      proteasomal inhibitor), indomethacin (cyclooxygenase inhibitor); and progesterone
      receptor antagonist (RU486). We have found that both RU486 and indomethacin does
      not disrupt the formation of the covalent linkage between the heavy chains of
      IalphaI to HA in the expanded OCC. In contrast, the inhibitors AG1478 and
      lapatinib prevent gonadotropin-induced cumulus expansion. Finally, the formation
      of oocyte-cumulus ECM relying on the covalent transfer of heavy chains of IalphaI
      molecules to HA has been inhibited in the presence of MG132.

PMID- 29346284
TI  - Double Heterozygosity for BRCA1 Pathogenic Variant and BRCA2 Polymorphic Stop
      Codon K3326X: A Case Report in a Southern Italian Family.
AB  - Here, we describe a patient with bilateral breast cancer and melanoma, and with a
      concomitant double variant, namely p.Gln563Ter in BRCA1 and p.Lys3326Ter in
      BRCA2. The BRCA2 p.Lys3326Ter (K3326X) (rs11571833) mutation identified in our
      patient is a debated substitution of thymidine for adenine which is currently
      regarded as benign polymorphism in main gene databases. Recent studies, however,
      describe this variant as associated with breast and ovarian tumors. Based on the
      observation of the cancer's earliest age of onset in this subject, our purpose
      was to reevaluate this variant according to recent papers indicating a role of
      powerful modifier of the genetic penetrance. Genetic testing was performed in all
      consenting patient's relatives, and in the collection of the clinical data
      particular attention was paid to the age of onset of the neoplasia. Following our
      observation that the our patient with double heterozygosis had an early age of
      onset for cancer similar to a few rare cases of double mutation for BRCA1 and
      BRCA2, we also performed an extensive review of the literature relative to
      patients carrying a double heterozygosity for both genes. In line with previous
      studies relative to the rare double heterozygosity in both BRCA1/2 genes, we
      found the earlier onset of breast cancer in our patient with both BRCA1/2
      mutations with respect to other relatives carrying the single BRCA1 mutation. The
      presence of the second K3326X variant in our case induces a phenotype
      characterized by early onset of the neoplasia in a manner similar to the other
      cases of double heterozygosity previously described. Therefore, we suggest that
      during the genetic counseling, it should be recommendable to evaluate the
      presence of the K3326X variant in association with other pathogenic mutations.

PMID- 29346285
TI  - Characterization of Odors of Wood by Gas Chromatography-Olfactometry with Removal
      of Extractives as Attempt to Control Indoor Air Quality.
AB  - Indoor air quality problems are usually revealed by occupants' complaints. In
      this study, the odors of two types of hardwood species, namely, Cathy poplar
      (Populus cathayana Rehd.) and rubberwood (Hevea brasiliensis) were selected and
      extracted with ethanol-toluene for removal of extractives in an attempt to
      eliminate the odors. The odorous components of neat and extracted woods were
      identified by gas chromatography-mass spectrometry/olfactometry (GC-MS/O). The
      results showed that about 33 kinds of key volatile compounds (peak area above
      0.2%) were detected from the GC-MS, and about 40 kinds of odorants were
      identified from GC-O. The components were concentrated between 15 and 33 min in
      GC-O, which was different from the concentration time in GC-MS. Lots of the odors
      identified from GC-O were unpleasant to humans, and variously described as
      stinky, burnt, leather, bug, herb, etc. These odors may originate from the
      thermos-oxidation of wood components. After extraction, the amounts and
      intensities of some odorants decreased, while some remained. However, the
      extraction process resulted in a benzene residue and led to increased benzene
      odor.

PMID- 29346286
TI  - A More Efficient Transportable and Scalable System for Real-Time Activities and
      Exercises Recognition.
AB  - Many people in the world are affected by muscle wasting, especially the
      population hits by myotonic dystrophy type 1 (DM1). Those people are usually
      given a program of multiple physical exercises to do. While DM1 and many other
      people have difficulties attending commercial centers to realize their program, a
      solution is to develop such a program completable at home. To this end, we
      developed a portable system that patients could bring home. This prototype is an
      improved version of the previous one using Wi-Fi, as this new prototype runs on
      BLE technology. This new prototype conceptualized induces great results.

PMID- 29346287
TI  - Development of Zika Virus Vaccines.
AB  - Zika virus (ZIKV) is a mosquito-borne flavivirus that emerged as a global threat
      following the most recent outbreak in Brazil in 2015. ZIKV infection of pregnant
      women is associated with fetal abnormalities such as microcephaly, and infection
      of adults can lead to Guillain-Barre syndrome, an autoimmune disease
      characterized by neurological deficits. Although there are currently licensed
      vaccines for other flaviviruses, there remains an urgent need for preventative
      vaccines against ZIKV infection. Herein we describe the current efforts to
      accelerate the development of ZIKV vaccines using various platforms, including
      live attenuated virus, inactivated virus, DNA and RNA, viral vectors, and in
      silico-predicted immunogenic viral epitopes. Many of these approaches have
      leveraged lessons learned from past experience with Dengue and other flavivirus
      vaccines.

PMID- 29346288
TI  - Application of Computational Intelligence to Improve Education in Smart Cities.
AB  - According to UNESCO, education is a fundamental human right and every nation's
      citizens should be granted universal access with equal quality to it. Because
      this goal is yet to be achieved in most countries, in particular in the
      developing and underdeveloped countries, it is extremely important to find more
      effective ways to improve education. This paper presents a model based on the
      application of computational intelligence (data mining and data science) that
      leads to the development of the student's knowledge profile and that can help
      educators in their decision making for best orienting their students. This model
      also tries to establish key performance indicators to monitor objectives'
      achievement within individual strategic planning assembled for each student. The
      model uses random forest for classification and prediction, graph description for
      data structure visualization and recommendation systems to present relevant
      information to stakeholders. The results presented were built based on the real
      dataset obtained from a Brazilian private k-9 (elementary school). The obtained
      results include correlations among key data, a model to predict student
      performance and recommendations that were generated for the stakeholders.

PMID- 29346289
TI  - Himawari-8 Satellite Based Dynamic Monitoring of Grassland Fire in China-Mongolia
      Border Regions.
AB  - In this study, we used bands 7, 4, and 3 of the Advance Himawari Imager (AHI)
      data, combined with a Threshold Algorithm and a visual interpretation method to
      monitor the entire process of grassland fires that occurred on the China-Mongolia
      border regions, between 05:40 (UTC) on April 19th to 13:50 (UTC) on April 21st
      2016. The results of the AHI data monitoring are evaluated by the fire point
      product data, the wind field data, and the environmental information data of the
      area in which the fire took place. The monitoring result shows that, the
      grassland fire burned for two days and eight hours with a total burned area of
      about 2708.29 km2. It mainly spread from the northwest to the southeast, with a
      maximum burning speed of 20.9 m/s, a minimum speed of 2.52 m/s, and an average
      speed of about 12.07 m/s. Thus, using AHI data can not only quickly and
      accurately track the dynamic development of a grassland fire, but also estimate
      the spread speed and direction. The evaluation of fire monitoring results reveals
      that AHI data with high precision and timeliness can be highly consistent with
      the actual situation.

PMID- 29346290
TI  - Joint Probabilistic Data Association Filter with Unknown Detection Probability
      and Clutter Rate.
AB  - This paper proposes a novel joint probabilistic data association (JPDA) filter
      for joint target tracking and track maintenance under unknown detection
      probability and clutter rate. The proposed algorithm consists of two main parts:
      (1) the standard JPDA filter with a Poisson point process birth model for multi
      object state estimation; and (2) a multi-Bernoulli filter for detection
      probability and clutter rate estimation. The performance of the proposed JPDA
      filter is evaluated through empirical tests. The results of the empirical tests
      show that the proposed JPDA filter has comparable performance with ideal JPDA
      that is assumed to have perfect knowledge of detection probability and clutter
      rate. Therefore, the algorithm developed is practical and could be implemented in
      a wide range of applications.

PMID- 29346291
TI  - Filaments Production and Fused Deposition Modelling of ABS/Carbon Nanotubes
      Composites.
AB  - Composite acrylonitrile-butadiene-styrene (ABS)/carbon nanotubes (CNT) filaments
      at 1, 2, 4, 6 and 8 wt %, suitable for fused deposition modelling (FDM) were
      obtained by using a completely solvent-free process based on direct melt
      compounding and extrusion. The optimal CNT content in the filaments for FDM was
      found to be 6 wt %; for this composite, a detailed investigation of the thermal,
      mechanical and electrical properties was performed. Presence of CNT in ABS
      filaments and 3D-printed parts resulted in a significant enhancement of the
      tensile modulus and strength, accompanied by a reduction of the elongation at
      break. As documented by dynamic mechanical thermal analysis, the stiffening
      effect of CNTs in ABS is particularly pronounced at high temperatures. Besides,
      the presence of CNT in 3D-printed parts accounts for better creep and thermal
      dimensional stabilities of 3D-printed parts, accompanied by a reduction of the
      coefficient of thermal expansion). 3D-printed nanocomposite samples with 6 wt %
      of CNT exhibited a good electrical conductivity, even if lower than pristine
      composite filaments.

PMID- 29346292
TI  - Isoform Sequencing and State-of-Art Applications for Unravelling Complexity of
      Plant Transcriptomes.
AB  - Single-molecule real-time (SMRT) sequencing developed by PacBio, also called
      third-generation sequencing (TGS), offers longer reads than the second-generation
      sequencing (SGS). Given its ability to obtain full-length transcripts without
      assembly, isoform sequencing (Iso-Seq) of transcriptomes by PacBio is
      advantageous for genome annotation, identification of novel genes and isoforms,
      as well as the discovery of long non-coding RNA (lncRNA). In addition, Iso-Seq
      gives access to the direct detection of alternative splicing, alternative
      polyadenylation (APA), gene fusion, and DNA modifications. Such applications of
      Iso-Seq facilitate the understanding of gene structure, post-transcriptional
      regulatory networks, and subsequently proteomic diversity. In this review, we
      summarize its applications in plant transcriptome study, specifically pointing
      out challenges associated with each step in the experimental design and highlight
      the development of bioinformatic pipelines. We aim to provide the community with
      an integrative overview and a comprehensive guidance to Iso-Seq, and thus to
      promote its applications in plant research.

PMID- 29346293
TI  - Fabry-Perot Interferometric High-Temperature Sensing Up to 1200  degrees C Based
      on a Silica Glass Photonic Crystal Fiber.
AB  - A Fabry-Perot interferometric sensor for temperature measurement was fabricated
      based on a silica glass solid-core photonic crystal fiber with a central air
      bore. By splicing a stub of photonic crystal fiber to a standard single-mode
      fiber, an intrinsic Fabry-Perot cavity was formed inside the photonic crystal
      fiber. Sensing experiment results show that the sensor can work stably for a
      consecutive 24 h under temperatures up to 1100  degrees C, and the short-term
      operation temperature can reach as high as 1200  degrees C (<30 min). In the
      measurement range of 300-1200  degrees C, the temperature sensitivity of the peak
      wavelength shift can reach as high as 15.61 pm/ degrees C, with a linearity of
      99.76%. The presented interferometric sensor is compact in size and possesses
      advantages such as an extended working range and high sensitivity, showing
      promising application prospects.

PMID- 29346294
TI  - GC-MS Analysis of the Volatile Constituents in the Leaves of 14 Compositae
      Plants.
AB  - The green organs, especially the leaves, of many Compositae plants possess
      characteristic aromas. To exploit the utility value of these germplasm resources,
      the constituents, mainly volatile compounds, in the leaves of 14 scented plant
      materials were qualitatively and quantitatively compared via gas chromatography
      mass spectrometry (GC-MS). A total of 213 constituents were detected and
      tentatively identified in the leaf extracts, and terpenoids (especially
      monoterpene and sesquiterpene derivatives), accounting for 40.45-90.38% of the
      total compounds, were the main components. The quantitative results revealed
      diverse concentrations and compositions of the chemical constituents between
      species. Principal component analysis (PCA) showed that different groups of these
      Compositae plants were characterized by main components of alpha-thujone,
      germacrene D, eucalyptol, beta-caryophyllene, and camphor, for example. On the
      other hand, cluster memberships corresponding to the molecular phylogenetic
      framework, were found by hierarchical cluster analysis (HCA) based on the
      terpenoid composition of the tested species. These results provide a
      phytochemical foundation for the use of these scented Compositae plants, and for
      the further study of the chemotaxonomy and differential metabolism of Compositae
      species.

PMID- 29346295
TI  - Peri-Elastodynamic Simulations of Guided Ultrasonic Waves in Plate-Like Structure
      with Surface Mounted PZT.
AB  - Peridynamic based elastodynamic computation tool named Peri-elastodynamics is
      proposed herein to simulate the three-dimensional (3D) Lamb wave modes in
      materials for the first time. Peri-elastodynamics is a nonlocal meshless approach
      which is a scale-independent generalized technique to visualize the acoustic and
      ultrasonic waves in plate-like structure, micro-electro-mechanical systems (MEMS)
      and nanodevices for their respective characterization. In this article, the
      characteristics of the fundamental Lamb wave modes are simulated in a sample
      plate-like structure. Lamb wave modes are generated using a surface mounted
      piezoelectric (PZT) transducer which is actuated from the top surface. The
      proposed generalized Peri-elastodynamics method is not only capable of simulating
      two dimensional (2D) in plane wave under plane strain condition formulated
      previously but also capable of accurately simulating the out of plane Symmetric
      and Antisymmetric Lamb wave modes in plate like structures in 3D. For structural
      health monitoring (SHM) of plate-like structures and nondestructive evaluation
      (NDE) of MEMS devices, it is necessary to simulate the 3D wave-damage interaction
      scenarios and visualize the different wave features due to damages. Hence, in
      addition, to simulating the guided ultrasonic wave modes in pristine material,
      Lamb waves were also simulated in a damaged plate. The accuracy of the proposed
      technique is verified by comparing the modes generated in the plate and the mode
      shapes across the thickness of the plate with theoretical wave analysis.

PMID- 29346296
TI  - Highly Sensitive Strain Sensor Based on a Novel Mach-Zehnder Interferometer with
      TCF-PCF Structure.
AB  - A highly sensitive strain sensor based on a novel fiber in line Mach-Zehnder
      interferometer (MZI) was demonstrated experimentally. The MZI was realized by
      splicing a section of photonic crystal fiber (PCF) with the same length of thin
      core fiber (TCF) between two single mode fibers (SMFs). The fringe visibility of
      MZI can reach as high as 20 dB in air. In particular, the strain sensitivity of 
      1.95 pm/MUepsilon was achieved within a range from 0 to 4000 MUepsilon.
      Furthermore, the strain properties of different length of MZI was investigated.
      It was found that the sensitivity was weekly dependent on the length of MZI. The
      strain sensitivities corresponding to the MZI with 35 mm PCF, 40 mm PCF and 45 mm
      PCF at 1550 nm band were -1.78 pm/MUepsilon, -1.73 pm/MUepsilon and -1.63
      pm/MUepsilon, respectively. Additionally, the sensor has advantages of simple
      fabrication, compact size and high sensitivity as well as good fringe visibility.

PMID- 29346297
TI  - The Dynamic Performance of Flexural Ultrasonic Transducers.
AB  - Flexural ultrasonic transducers are principally used as proximity sensors and for
      industrial metrology. Their operation relies on a piezoelectric ceramic to
      generate a flexing of a metallic membrane, which delivers the ultrasound signal.
      The performance of flexural ultrasonic transducers has been largely limited to
      excitation through a short voltage burst signal at a designated mechanical
      resonance frequency. However, a steady-state amplitude response is not generated
      instantaneously in a flexural ultrasonic transducer from a drive excitation
      signal, and differences in the drive characteristics between transmitting and
      receiving transducers can affect the measured response. This research
      investigates the dynamic performance of flexural ultrasonic transducers using
      acoustic microphone measurements and laser Doppler vibrometry, supported by a
      detailed mechanical analog model, in a process which has not before been applied
      to the flexural ultrasonic transducer. These techniques are employed to gain
      insights into the physics of their vibration behaviour, vital for the
      optimisation of industrial ultrasound systems.

PMID- 29346298
TI  - Motion Tracking System for Robust Non-Contact Blood Perfusion Sensor.
AB  - We propose a motion-robust laser Doppler flowmetry (LDF) system that can be used
      as a non-contact blood perfusion sensor for medical diagnosis. Endoscopic LDF
      systems are typically limited in their usefulness in clinical contexts by the
      need for the natural organs to be immobilized, as serious motion artifacts due to
      the axial surface displacement can interfere with blood perfusion measurements.
      In our system, the focusing lens moves to track the motion of the target using a
      low-frequency reference signal in the optical data, enabling the suppression of
      these motion artifacts in the axial direction. This paper reports feasibility
      tests on a prototype of this system using a microfluidic phantom as a measurement
      target moving in the direction of the optical axis. The frequency spectra
      detected and the perfusion values calculated from those spectra show that the
      motion tracking system is capable of suppressing motion artifacts in perfusion
      readings. We compared the prototype LDF system's measurements with and without
      motion feedback, and found that motion tracking improves the fidelity of the
      perfusion signal by as much as 87%.

PMID- 29346299
TI  - Meteo and Hydrodynamic Measurements to Detect Physical Processes in Confined
      Shallow Seas.
AB  - Coastal sites with typical lagoon features are extremely vulnerable, often
      suffering from scarce circulation. Especially in the case of shallow basins
      subjected to strong anthropization and urban discharges, it is fundamental to
      monitor their hydrodynamics and water quality. The proper detection of events by
      high performance sensors and appropriate analysis of sensor signals has proved to
      be a necessary tool for local authorities and stakeholders, leading to early
      warning and preventive measures against environmental degradation and related
      hazards. At the same time, assessed datasets are not only essential to deepen the
      knowledge of the physical processes in the target basin, but are also necessary
      to calibrate and validate modelling systems providing forecasts. The present
      paper aims to show how long-term and continuous recordings of meteorological and
      hydrodynamic data, collected in a semi-enclosed sea, can be managed to rapidly
      provide fundamental insights on its hydrodynamic structure. The acquired signals
      have been analyzed in time domain, processed and finally, correlated. The adopted
      method is simple, feasible and easily replicable. Even if the results are site
      dependent, the procedure is generic, and depends on having good quality available
      data. To show how this might be employed, a case study is examined. In fact, it
      has been applied to a coastal system, located in Southern Italy, where two
      monitoring stations are placed in two interconnected basins. The inferred results
      show that the system is not wind dominated, and that the annual trends in the
      wind regime, wave spreading and current circulation are not independent, but
      rather reiterate. These deductions are of great interest as a predictive
      perspective and for numerical modelling.

PMID- 29346300
TI  - Trapezium Bone Density-A Comparison of Measurements by DXA and CT.
AB  - Bone density may influence the primary fixation of cementless implants, and poor
      bone density may increase the risk of implant failure. Before deciding on using
      total joint replacement as treatment in osteoarthritis of the trapeziometacarpal
      joint, it is valuable to determine the trapezium bone density. The aim of this
      study was to: (1) determine the correlation between measurements of bone mineral
      density of the trapezium obtained by dual-energy X-ray absorptiometry (DXA) scans
      by a circumference method and a new inner-ellipse method; and (2) to compare
      those to measurements of bone density obtained by computerized tomography (CT)
      scans in Hounsfield units (HU). We included 71 hands from 59 patients with a mean
      age of 59 years (43-77). All patients had Eaton-Glickel stage II-IV
      trapeziometacarpal (TM) joint osteoarthritis, were under evaluation for
      trapeziometacarpal total joint replacement, and underwent DXA and CT wrist scans.
      There was an excellent correlation (r = 0.94) between DXA bone mineral density
      measures using the circumference and the inner-ellipse method. There was a
      moderate correlation between bone density measures obtained by DXA- and CT-scans
      with (r = 0.49) for the circumference method, and (r = 0.55) for the inner
      ellipse method. DXA may be used in pre-operative evaluation of the trapezium bone
      quality, and the simpler DXA inner-ellipse measurement method can replace the DXA
      circumference method in estimation of bone density of the trapezium.

PMID- 29346302
TI  - Smart Device-Based Notifications to Promote Healthy Behavior Related to Childhood
      Obesity and Overweight.
AB  - Obesity is one of the most serious public health challenges of the 21st century
      and it is a threat to the life of people according to World Health Organization.
      In this scenario, family environment is important to establish healthy habits
      which help to reduce levels of obesity and control overweight in children.
      However, little efforts have been focused on helping parents to promote and have
      healthy lifestyles. In this paper, we present two smart device-based notification
      prototypes to promote healthy behavior with the aim of avoiding childhood
      overweight and obesity. The first prototype helps parents to follow a healthy
      snack routine, based on a nutritionist suggestion. Using a fridge magnet, parents
      receive graphical reminders of which snacks they and their children should
      consume. The second prototype provides a graphical reminder that prevents parents
      from forgetting the required equipment to practice sports. Prototypes were
      evaluated by nine nutritionists from three countries (Costa Rica, Mexico and
      Spain). Evaluations were based on anticipation of use and the ergonomics of human
      system interaction according to the ISO 9241-210. Results show that the system is
      considered useful. Even though they might not be willing to use the system, they
      would recommend it to their patients. Based on the ISO 9241-210 the best ranked
      features were the system's comprehensibility, the perceived effectiveness and
      clarity. The worst ranked features were the system's suitability for learning and
      its discriminability.

PMID- 29346301
TI  - BRAF and MEK Inhibitors Influence the Function of Reprogrammed T Cells:
      Consequences for Adoptive T-Cell Therapy.
AB  - BRAF and MEK inhibitors (BRAFi/MEKi), the standard treatment for patients with
      BRAFV600 mutated melanoma, are currently explored in combination with various
      immunotherapies, notably checkpoint inhibitors and adoptive transfer of receptor
      transfected T cells. Since two BRAFi/MEKi combinations with similar efficacy are
      approved, potential differences in their effects on immune cells would enable a
      rational choice for triple therapies. Therefore, we characterized the influence
      of the clinically approved BRAFi/MEKi combinations dabrafenib (Dabra) and
      trametinib (Tram) vs. vemurafenib (Vem) and cobimetinib (Cobi) on the activation
      and functionality of chimeric antigen receptor (CAR)-transfected T cells. We co
      cultured CAR-transfected CD8+ T cells and target cells with clinically relevant
      concentrations of the inhibitors and determined the antigen-induced cytokine
      secretion. All BRAFi/MEKi reduced this release as single agents, with Dabra
      having the mildest inhibitory effect, and Dabra + Tram having a clearly milder
      inhibitory effect than Vem + Cobi. A similar picture was observed for the
      upregulation of the activation markers CD25 and CD69 on CAR-transfected T cells
      after antigen-specific stimulation. Most importantly, the cytolytic capacity of
      the CAR-T cells was significantly inhibited by Cobi and Vem + Cobi, whereas the
      other kinase inhibitors showed no effect. Therefore, the combination Dabra + Tram
      would be more suitable for combining with T-cell-based immunotherapy than Vem +
      Cobi.

PMID- 29346303
TI  - Micro-Spherical Sulfur/Graphene Oxide Composite via Spray Drying for High
      Performance Lithium Sulfur Batteries.
AB  - An efficient, industry-accepted spray drying method was used to synthesize micro
      spherical sulfur/graphene oxide (S/GO) composites as cathode materials within
      lithium sulfur batteries. The as-designed wrapping of the sulfur-nanoparticles,
      with wrinkled GO composites, was characterized by scanning electron microscopy
      (SEM) and transmission electron microscopy (TEM). The unique morphological design
      of this material enabled superior discharge capacity and cycling performance,
      demonstrating a high initial discharge capacity of 1400 mAh g-1 at 0.1 C. The
      discharge capacity remained at 828 mAh g-1 after 150 cycles. The superior
      electrochemical performance indicates that the S/GO composite improves electrical
      conductivity and alleviates the shuttle effect. This study represents the first
      time such a facile spray drying method has been adopted for lithium sulfur
      batteries and used in the fabrication of S/GO composites.

PMID- 29346304
TI  - 'Total Pain' in Children with Severe Neurological Impairment.
AB  - Many children with palliative care needs experience difficulty in managing pain.
      Perhaps none more so than those with severe neurological impairment. For many
      years; behaviours in these children were misunderstood. As a result; pain was
      poorly recognised and inadequately managed. Significant advances have been made
      in the assessment and management of pain in this challenging group of patients.
      We summarise these advances; drawing on our own experience working with infants;
      children and young adults with palliative care needs within a UK tertiary
      paediatric palliative care service. We expand on the recent understanding of
      'Total Pain'; applying a holistic approach to pain assessment and management in
      children with severe neurological impairment.

PMID- 29346305
TI  - The Sustainable Development Assessment of Reservoir Resettlement Based on a BP
      Neural Network.
AB  - Resettlement affects not only the resettlers' production activities and life but
      also, directly or indirectly, the normal operation of power stations, the
      sustainable development of the resettlers, and regional social stability.
      Therefore, a scientific evaluation index system for the sustainable development
      of reservoir resettlement must be established that fits Chinese national
      conditions and not only promotes reservoir resettlement research but also
      improves resettlement practice. This essay builds an evaluation index system for
      resettlers' sustainable development based on a back-propagation (BP) neural
      network, which can be adopted in China, taking the resettlement necessitated by
      step hydropower stations along the Wujiang River cascade as an example. The
      assessment results show that the resettlement caused by step power stations along
      the Wujiang River is sustainable, and this evaluation supports the conclusion
      that national policies and regulations, which are undergoing constant
      improvement, and resettlement has increasingly improved. The results provide a
      reference for hydropower reservoir resettlement in developing countries.

PMID- 29346306
TI  - Zinc Tantalum Oxynitride (ZnTaO2N) Photoanode Modified with Cobalt Phosphate
      Layers for the Photoelectrochemical Oxidation of Alkali Water.
AB  - Photoanodes fabricated by the electrophoretic deposition of a thermally prepared
      zinc tantalum oxynitride (ZnTaO2N) catalyst onto indium tin oxide (ITO)
      substrates show photoactivation for the oxygen evolution reaction (OER) in
      alkaline solutions. The photoactivity of the OER is further boosted by the
      photodeposition of cobalt phosphate (CoPi) layers onto the surface of the ZnTaO2N
      photoanodes. Structural, morphological, and photoelectrochemical (PEC) properties
      of the modified ZnTaO2N photoanodes are studied using X-ray diffraction (XRD),
      scanning electron microscopy (SEM), ultraviolet visible (UV-Vis) diffuse
      reflectance spectroscopy, and electrochemical techniques. The presence of the
      CoPi layer significantly improved the PEC performance of water oxidation in an
      alkaline sulphate solution. The photocurrent-voltage behavior of the CoPi
      modified ZnTaO2N anodes was improved, with the influence being more prominent at
      lower oxidation potentials. A stable photocurrent density of about 2.3 mA.cm-2 at
      1.23 V vs. RHE was attained upon visible light illumination. Relative to the
      ZnTaO2N photoanodes, an almost three-fold photocurrent increase was achieved at
      the CoPi/ZnTaO2N photoelectrode. Perovskite-based oxynitrides are modified using
      an oxygen-evolution co-catalyst of CoPi, and provide a new dimension for
      enhancing the photoactivity of oxygen evolution in solar-assisted water-splitting
      reactions.

PMID- 29346307
TI  - Knowledge and Attitudes of General Practitioners and Sexual Health Care
      Professionals Regarding Human Papillomavirus Vaccination for Young Men Who Have
      Sex with Men.
AB  - Men who have sex with men (MSM) may be at higher risk for human papillomavirus
      (HPV)-associated cancers. Healthcare professionals' recommendations can affect
      HPV vaccination uptake. Since 2016, MSM up to 45 years have been offered HPV
      vaccination at genitourinary medicine (GUM) clinics in a pilot programme, and
      primary care was recommended as a setting for opportunistic vaccination.
      Vaccination prior to potential exposure to the virus (i.e., sexual debut) is
      likely to be most efficacious, therefore a focus on young MSM (YMSM) is
      important. This study aimed to explore and compare the knowledge and attitudes of
      UK General Practitioners (GPs) and sexual healthcare professionals (SHCPs)
      regarding HPV vaccination for YMSM (age 16-24). A cross-sectional study using an
      online questionnaire examined 38 GPs and 49 SHCPs, including 59 (67.82%) females
      with a mean age of 40.71 years. Twenty-two participants (20 SHCPs, p < 0.001) had
      vaccinated a YMSM patient against HPV. GPs lack of time (25/38, 65.79%) and SHCP
      staff availability (27/49, 55.10%) were the main reported factors preventing YMSM
      HPV vaccination. GPs were less likely than SHCPs to believe there was sufficient
      evidence for vaccinating YMSM (OR = 0.02, 95% CI = 0.01, 0.47); less likely to
      have skills to identify YMSM who may benefit from vaccination (OR = 0.03, 95% CI
      = 0.01, 0.15); and less confident recommending YMSM vaccination (OR = 0.01, 95%
      CI = 0.00, 0.01). GPs appear to have different knowledge, attitudes, and skills
      regarding YMSM HPV vaccination when compared to SHCPs.

PMID- 29346310
TI  - AR Signaling in Human Malignancies: Prostate Cancer and Beyond.
AB  - The notion that androgens and androgen receptor (AR) signaling are the hallmarks
      of prostate cancer oncogenesis and disease progression is generally well
      accepted. What is more poorly understood is the role of AR signaling in other
      human malignancies. This special issue of Cancers initially reviews the role of
      AR in advanced prostate cancer, and then explores the potential importance of AR
      signaling in other epithelial malignancies. The first few articles focus on the
      use of novel AR-targeting therapies in castration-resistant prostate cancer and
      the mechanisms of resistance to novel antiandrogens, and they also outline the
      interaction between AR and other cellular pathways, including PI3 kinase
      signaling, transcriptional regulation, angiogenesis, stromal factors, Wnt
      signaling, and epigenetic regulation in prostate cancer. The next several
      articles review the possible role of androgens and AR signaling in breast cancer,
      bladder cancer, salivary gland cancer, and hepatocellular carcinoma, as well as
      the potential treatment implications of using antiandrogen therapies in these non
      prostatic malignancies.

PMID- 29346308
TI  - Tissue Engineering to Improve Immature Testicular Tissue and Cell Transplantation
      Outcomes: One Step Closer to Fertility Restoration for Prepubertal Boys Exposed
      to Gonadotoxic Treatments.
AB  - Despite their important contribution to the cure of both oncological and benign
      diseases, gonadotoxic therapies present the risk of a severe impairment of
      fertility. Sperm cryopreservation is not an option to preserve prepubertal boys'
      reproductive potential, as their seminiferous tubules only contain spermatogonial
      stem cells (as diploid precursors of spermatozoa). Cryobanking of human immature
      testicular tissue (ITT) prior to gonadotoxic therapies is an accepted practice.
      Evaluation of cryopreserved ITT using xenotransplantation in nude mice showed the
      survival of a limited proportion of spermatogonia and their ability to
      proliferate and initiate differentiation. However, complete spermatogenesis could
      not be achieved in the mouse model. Loss of germ cells after ITT grafting points
      to the need to optimize the transplantation technique. Tissue engineering, a new
      branch of science that aims at improving cellular environment using scaffolds and
      molecules administration, might be an approach for further progress. In this
      review, after summarizing the lessons learned from human prepubertal testicular
      germ cells or tissue xenotransplantation experiments, we will focus on the
      benefits that might be gathered using bioengineering techniques to enhance
      transplantation outcomes by optimizing early tissue graft revascularization,
      protecting cells from toxic insults linked to ischemic injury and exploring
      strategies to promote cellular differentiation.

PMID- 29346309
TI  - The Role of E6 Spliced Isoforms (E6*) in Human Papillomavirus-Induced
      Carcinogenesis.
AB  - Persistent infections with High Risk Human Papillomaviruses (HR-HPVs) are the
      main cause of cervical cancer development. The E6 and E7 oncoproteins of HR-HPVs
      are derived from a polycistronic pre-mRNA transcribed from an HPV early promoter.
      Through alternative splicing, this pre-mRNA produces a variety of E6 spliced
      transcripts termed E6*. In pre-malignant lesions and HPV-related cancers,
      different E6/E6* transcriptional patterns have been found, although they have not
      been clearly associated to cancer development. Moreover, there is a controversy
      about the participation of E6* proteins in cancer progression. This review
      addresses the regulation of E6 splicing and the different functions that have
      been found for E6* proteins, as well as their possible role in HPV-induced
      carcinogenesis.

PMID- 29346312
TI  - Sidewalk Landscape Structure and Thermal Conditions for Child and Adult
      Pedestrians.
AB  - Walking is being promoted for health and transportation purposes across all
      climatic regions in the US and beyond. Despite this, an uncomfortable
      microclimate condition along sidewalks is one of the major deterrents of walking,
      and more empirical research is needed to determine the risks of heat exposure to
      pedestrians while walking. This study examined the effect of street trees and
      grass along sidewalks on air temperatures. A series of thermal images were taken
      at the average heights of adults and children in the US to objectively measure
      the air temperatures of 10 sidewalk segments in College Station, TX, USA. After
      controlling the other key physical environmental conditions, sidewalks with more
      trees or wider grass buffer areas had lower air temperatures than those with less
      vegetation. Children were exposed to higher temperatures due to the greater
      exposure or proximity to the pavement surface, which tends to have higher radiant
      heat. Multivariate regression analysis suggested that the configuration of trees
      and grass buffers along the sidewalks helped to promote pleasant thermal
      conditions and reduced the differences in ambient air temperatures measured at
      child and adult heights. This study suggests that street trees and vegetated
      ground help reduce the air temperatures, leading to more thermally comfortable
      environments for both child and adult pedestrians in warm climates. The thermal
      implications of street landscape require further attention by researchers and
      policy makers that are interested in promoting outdoor walking.

PMID- 29346313
TI  - A Comparison of the Chemical Composition, In Vitro Bioaccessibility and
      Antioxidant Activity of Phenolic Compounds from Rice Bran and Its Dietary Fibres.
AB  - The composition, in vitro bioaccessibility and antioxidant activities of the
      phenolic compounds in defatted rice bran (DRB) and its soluble and insoluble
      dietary fibres were systematically evaluated in this study. The total phenolic
      content of insoluble dietary fibre from DRB (IDFDRB) was much higher than that of
      the soluble dietary fibre from DRB (SDFDRB) but was 10% lower than that of DRB.
      Bound phenolics accounted for more than 90% of the total phenolics in IDFDRB,
      whereas they accounted for 34.2% and 40.5% of the total phenolics in DRB and
      SDFDRB, respectively. Additionally, the phenolic profiles and antioxidant
      activities were significantly different in DRB, SDFDRB and IDFDRB. The phenolic
      compounds in IDFDRB were much less bioaccessibility than those in DRB and SDFDRB
      due to the higher proportion of bound phenolics in IDFDRB. Considering that bound
      phenolics could be released from food matrices by bacterial enzymes in the large
      intestine and go on to exert significant beneficial health effects in vivo,
      further studies on IDFDRB are needed to investigate the release of the phenolics
      from IDFDRB via gut microbiota and the related health benefits.

PMID- 29346311
TI  - Apoptotic and Nonapoptotic Activities of Pterostilbene against Cancer.
AB  - Cancer is a major cause of death. The outcomes of current therapeutic strategies
      against cancer often ironically lead to even increased mortality due to the
      subsequent drug resistance and to metastatic recurrence. Alternative medicines
      are thus urgently needed. Cumulative evidence has pointed out that pterostilbene
      (trans-3,5-dimethoxy-4-hydroxystilbene, PS) has excellent pharmacological
      benefits for the prevention and treatment for various types of cancer in their
      different stages of progression by evoking apoptotic or nonapoptotic anti-cancer
      activities. In this review article, we first update current knowledge regarding
      tumor progression toward accomplishment of metastasis. Subsequently, we review
      current literature regarding the anti-cancer activities of PS. Finally, we
      provide future perspectives to clinically utilize PS as novel cancer therapeutic
      remedies. We, therefore, conclude and propose that PS is one ideal alternative
      medicine to be administered in the diet as a nutritional supplement.

PMID- 29346314
TI  - Sustainable Transportation Attitudes and Health Behavior Change: Evaluation of a
      Brief Stage-Targeted Video Intervention.
AB  - Promoting physical activity and sustainable transportation is essential in the
      face of rising health care costs, obesity rates, and other public health threats
      resulting from lack of physical activity. Targeted communications can encourage
      distinct population segments to adopt active and sustainable transportation
      modes. Our work is designed to promote the health, social, and environmental
      benefits of sustainable/active transportation (ST) using the Transtheoretical
      Model of Change (TTM), which has been successfully applied to a range of health,
      and more recently, sustainability behaviors. Earlier, measurement development
      confirmed both the structure of ST pros and cons and efficacy measures as well as
      the relationship between these constructs and ST stages of change, replicating
      results found for many other behaviors. The present paper discusses a brief pre
      post video pilot intervention study designed for precontemplators and
      contemplators (N = 604) that was well received, effective in moving respondents
      towards increased readiness for ST behavior change, and improving some ST
      attitudes, significantly reducing the cons of ST. This research program shows
      that a brief stage-targeted behavior change video can increase readiness and
      reduce the cons for healthy transportation choices.

PMID- 29346315
TI  - Dietary Total Prenylflavonoids from the Fruits of Psoralea corylifolia L.
      Prevents Age-Related Cognitive Deficits and Down-Regulates Alzheimer's Markers in
      SAMP8 Mice.
AB  - Alzheimer's disease (AD) is a serious threat for the aging society. In this
      study, we examined the preventive effect of the total prenylflavonoids (TPFB)
      prepared from the dried fruits of Psoralea corylifolia L., using an age-related
      AD mouse model SAMP8. We found that long-term dietary TPFB at 50 mg/kg.day
      significantly improved cognitive performance of the SAMP8 mice in Morris water
      maze tests, similar to 150 mg/kg.day of resveratrol, a popular neuro-protective
      compound. Furthermore, TPFB treatment showed significant improvements in various
      AD markers in SAMP8 brains, which were restored to near control levels of the
      normal mice, SAMR1. TPFB significantly reduced the level of amyloid beta-peptide
      42 (Abeta42), inhibited hyperphosphorylation of the microtubule-associated
      protein Tau, induced phosphorylation of Ser9 of the glycogen synthase kinase
      3beta (GSK-3beta), and decreased the expression of the proinflammatory cytokines
      TNFalpha, IL-6, and IL-1beta. Finally, TPFB also markedly reduced the level of
      serum derivatives of reactive oxygen metabolites (d-ROMs), a biomarker of
      oxidative stress in vivo. These results showed that dietary TPFB could
      effectively prevent age-related cognitive deficits and AD-like neurobiochemical
      changes, and may have a potential role in the prevention of Alzheimer's disease.

PMID- 29346316
TI  - Chronic Dietary Intake of Enniatin B in Broiler Chickens Has Low Impact on
      Intestinal Morphometry and Hepatic Histology, and Shows Limited Transfer to Liver
      Tissue.
AB  - The Fusarium mycotoxin enniatin B (ENN B) is a so-called emerging mycotoxin
      frequently contaminating poultry feed. To investigate the impact of chronic ENN B
      exposure on animal health, broiler chickens were fed either a diet naturally
      contaminated with ENN B (2352 ug/kg) or a control diet (135 ug/kg) for 2, 7, 14,
      or 21 days. ENN B concentrations were determined in plasma and liver using a
      validated ultra-high performance liquid chromatography-tandem mass spectrometry
      UHPLC-MS/MS method. Liver was evaluated histologically, and the villus length and
      crypt depth of the duodenum, jejunum, and ileum were measured. Histopathology of
      the livers did not reveal major abnormalities. Feeding an ENN B-contaminated diet
      could possibly inhibit the proliferation of enterocytes in the duodenal crypts,
      but did not affect villus length, crypt depth, or villus length-crypt depth ratio
      of the jejunum and ileum. ENN B levels in plasma and liver were significantly
      higher in the ENN B-fed group and ranged between <25-264 pg/mL and <0.05-0.85
      ng/g, respectively. ENN B carry-over rates from feed to liver tissue were 0.005
      0.014% and 0.034-0.109% in the ENN B and control group, respectively. Carry-over
      rates were low and indicated a limited contribution of poultry tissue-derived
      products to the total dietary ENN B intake for humans. The above results support
      the opinion of the European Food Safety Authority stating that adverse health
      effects from ENN B in broiler chickens are unlikely.

PMID- 29346318
TI  - Differences between Outdoor and Indoor Sound Levels for Open, Tilted, and Closed
      Windows.
AB  - Noise exposure prediction models for health effect studies normally estimate free
      field exposure levels outside. However, to assess the noise exposure inside
      dwellings, an estimate of indoor sound levels is necessary. To date, little field
      data is available about the difference between indoor and outdoor noise levels
      and factors affecting the damping of outside noise. This is a major cause of
      uncertainty in indoor noise exposure prediction and may lead to exposure
      misclassification in health assessments. This study aims to determine sound level
      differences between the indoors and the outdoors for different window positions
      and how this sound damping is related to building characteristics. For this
      purpose, measurements were carried out at home in a sample of 102 Swiss residents
      exposed to road traffic noise. Sound pressure level recordings were performed
      outdoors and indoors, in the living room and in the bedroom. Three scenarios-of
      open, tilted, and closed windows-were recorded for three minutes each. For each
      situation, data on additional parameters such as the orientation towards the
      source, floor, and room, as well as sound insulation characteristics were
      collected. On that basis, linear regression models were established. The median
      outdoor-indoor sound level differences were of 10 dB(A) for open, 16 dB(A) for
      tilted, and 28 dB(A) for closed windows. For open and tilted windows, the most
      relevant parameters affecting the outdoor-indoor differences were the position of
      the window, the type and volume of the room, and the age of the building. For
      closed windows, the relevant parameters were the sound level outside, the
      material of the window frame, the existence of window gaskets, and the number of
      windows.

PMID- 29346317
TI  - Liposomal TriCurin, A Synergistic Combination of Curcumin, Epicatechin Gallate
      and Resveratrol, Repolarizes Tumor-Associated Microglia/Macrophages, and
      Eliminates Glioblastoma (GBM) and GBM Stem Cells.
AB  - Glioblastoma (GBM) is a deadly brain tumor with a current mean survival of 12-15
      months. Despite being a potent anti-cancer agent, the turmeric ingredient
      curcumin (C) has limited anti-tumor efficacy in vivo due to its low
      bioavailability. We have reported earlier a strategy involving the use two other
      polyphenols, epicatechin gallate (E) from green tea and resveratrol (R) from red
      grapes at a unique, synergistic molar ratio with C (C:E:R: 4:1:12.5, termed
      TriCurin) to achieve superior potency against HPV+ tumors than C alone at C:E:R
      (MUM): 32:8:100 (termed 32 MUM+ TriCurin). We have now prepared liposomal
      TriCurin (TrLp) and demonstrated that TrLp boosts activated p53 in cultured GL261
      mouse GBM cells to trigger apoptosis of GBM and GBM stem cells in vitro. TrLp
      administration into mice yielded a stable plasma concentration of 210 nM C for 60
      min, which, though sub-lethal for cultured GL261 cells, was able to cause
      repolarization of M2-like tumor (GBM)-associated microglia/macrophages to the
      tumoricidal M1-like phenotype and intra-GBM recruitment of activated natural
      killer cells. The intratumor presence of such tumoricidal immune cells was
      associated with concomitant suppression of tumor-load, and apoptosis of GBM and
      GBM stem cells. Thus, TrLp is a potential onco-immunotherapeutic agent against
      GBM tumors.

PMID- 29346319
TI  - Hierarchical Discriminant Analysis.
AB  - The Internet of Things (IoT) generates lots of high-dimensional sensor
      intelligent data. The processing of high-dimensional data (e.g., data
      visualization and data classification) is very difficult, so it requires
      excellent subspace learning algorithms to learn a latent subspace to preserve the
      intrinsic structure of the high-dimensional data, and abandon the least useful
      information in the subsequent processing. In this context, many subspace learning
      algorithms have been presented. However, in the process of transforming the high
      dimensional data into the low-dimensional space, the huge difference between the
      sum of inter-class distance and the sum of intra-class distance for distinct data
      may cause a bias problem. That means that the impact of intra-class distance is
      overwhelmed. To address this problem, we propose a novel algorithm called
      Hierarchical Discriminant Analysis (HDA). It minimizes the sum of intra-class
      distance first, and then maximizes the sum of inter-class distance. This proposed
      method balances the bias from the inter-class and that from the intra-class to
      achieve better performance. Extensive experiments are conducted on several
      benchmark face datasets. The results reveal that HDA obtains better performance
      than other dimensionality reduction algorithms.

PMID- 29346321
TI  - New Control Paradigms for Resources Saving: An Approach for Mobile Robots
      Navigation.
AB  - In this work, an event-based control scheme is presented. The proposed system has
      been developed to solve control problems appearing in the field of Networked
      Control Systems (NCS). Several models and methodologies have been proposed to
      measure different resources consumptions. The use of bandwidth, computational
      load and energy resources have been investigated. This analysis shows how the
      parameters of the system impacts on the resources efficiency. Moreover, the
      proposed system has been compared with its equivalent discrete-time solution. In
      the experiments, an application of NCS for mobile robots navigation has been set
      up and its resource usage efficiency has been analysed.

PMID- 29346320
TI  - C-Phycocyanin and Phycocyanobilin as Remyelination Therapies for Enhancing
      Recovery in Multiple Sclerosis and Ischemic Stroke: A Preclinical Perspective.
AB  - Myelin loss has a crucial impact on behavior disabilities associated to Multiple
      Sclerosis (MS) and Ischemic Stroke (IS). Although several MS therapies are
      approved, none of them promote remyelination in patients, limiting their ability
      for chronic recovery. With no available therapeutic options, enhanced
      demyelination in stroke survivors is correlated with a poorer behavioral
      recovery. Here, we show the experimental findings of our group and others
      supporting the remyelinating effects of C-Phycocyanin (C-PC), the main
      biliprotein of Spirulina platensis and its linked tetrapyrrole Phycocyanobilin
      (PCB), in models of these illnesses. C-PC promoted white matter regeneration in
      rats and mice affected by experimental autoimmune encephalomyelitis. Electron
      microscopy analysis in cerebral cortex from ischemic rats revealed a potent
      remyelinating action of PCB treatment after stroke. Among others biological
      processes, we discussed the role of regulatory T cell induction, the control of
      oxidative stress and pro-inflammatory mediators, gene expression modulation and
      COX-2 inhibition as potential mechanisms involved in the C-PC and PCB effects on
      the recruitment, differentiation and maturation of oligodendrocyte precursor
      cells in demyelinated lesions. The assembled evidence supports the implementation
      of clinical trials to demonstrate the recovery effects of C-PC and PCB in these
      diseases.

PMID- 29346322
TI  - Regioselective Synthesis of Procyanidin B6, A 4-6-Condensed (+)-Catechin Dimer,
      by Intramolecular Condensation.
AB  - Proanthocyanidins, also known as condensed tannins or oligomeric flavonoids, are
      found in many edible plants and exhibit interesting biological activities.
      Herein, we report a new, simple method for the stereoselective synthesis of
      procyanidin B6, a (+)-catechin-(4-6)-(+)-catechin dimer, by Lewis acid-catalyzed
      intramolecular condensation. The 5-O-t-butyldimethylsilyl (TBDMS) group of
      5,7,3'4'-tetra-O-TBDMS-(+)-catechin was regioselectively removed using
      trifluoroacetic acid, leading to the "regio-controlled" synthesis of procyanidin
      B6. The 5-hydroxyl group of the 7,3',4'-tri-O-TBDMS-(+)-catechin nucleophile and
      the 3-hydroxyl group of 5,7,3',4'-tetra-O-benzylated-(+)-catechin electrophile
      were connected with an azelaic acid. The subsequent SnCl4-catalyzed
      intramolecular condensation proceeded smoothly to give the 4-6-condensed catechin
      dimer. This is the first report on the complete regioselective synthesis of a 4-6
      connected oligomer without modifying the 8-position.

PMID- 29346323
TI  - Sculling Compensation Algorithm for SINS Based on Two-Time Scale Perturbation
      Model of Inertial Measurements.
AB  - In order to decrease the velocity sculling error under vibration environments, a
      new sculling error compensation algorithm for strapdown inertial navigation
      system (SINS) using angular rate and specific force measurements as inputs is
      proposed in this paper. First, the sculling error formula in incremental velocity
      update is analytically derived in terms of the angular rate and specific force.
      Next, two-time scale perturbation models of the angular rate and specific force
      are constructed. The new sculling correction term is derived and a gravitational
      search optimization method is used to determine the parameters in the two-time
      scale perturbation models. Finally, the performance of the proposed algorithm is
      evaluated in a stochastic real sculling environment, which is different from the
      conventional algorithms simulated in a pure sculling circumstance. A series of
      test results demonstrate that the new sculling compensation algorithm can achieve
      balanced real/pseudo sculling correction performance during velocity update with
      the advantage of less computation load compared with conventional algorithms.

PMID- 29346325
TI  - Synthesis and Antimicrobial Activity of 4-Substituted 1,2,3-Triazole-Coumarin
      Derivatives.
AB  - A new series of coumarin-1,2,3-triazole conjugates with varied alkyl, phenyl and
      heterocycle moieties at C-4 of the triazole nucleus were synthesized using a
      copper(I)-catalysed Huisgen 1,3-dipolar cycloaddition reaction of corresponding O
      propargylated coumarin (3) or N-propargylated coumarin (6) with alkyl or aryl
      azides. Based on their minimal inhibitory concentrations (MICs) against selected
      microorganisms, six out of twenty-six compounds showed significant antibacterial
      activity towards Enterococcus faecalis (MIC = 12.5-50 ug/mL). Moreover, the
      synthesized triazoles show relatively low toxicity against human erythrocytes.

PMID- 29346326
TI  - Lipid Membrane Nanosensors for Environmental Monitoring: The Art, the
      Opportunities, and the Challenges.
AB  - The advent of nanotechnology has brought along new materials, techniques, and
      concepts, readily adaptable to lipid membrane-based biosensing. The transition
      from micro-sensors to nano-sensors is neither straightforward nor effortless, yet
      it leads to devices with superior analytical characteristics: ultra-low
      detectability, small sample volumes, better capabilities for integration, and
      more available bioelements and processes. Environmental monitoring remains a
      complicated field dealing with a large variety of pollutants, several
      decomposition products, or secondary chemicals produced ad hoc in the short- or
      medium term, many sub-systems affected variously, and many processes largely
      unknown. The new generation of lipid membranes, i.e., nanosensors, has the
      potential for developing monitors with site-specific analytical performance and
      operational stability, as well as analyte-tailored types of responses. This
      review presents the state-of-the art, the opportunities for niche applicability,
      and the challenges that lie ahead.

PMID- 29346327
TI  - Enhanced Isotopic Ratio Outlier Analysis (IROA) Peak Detection and Identification
      with Ultra-High Resolution GC-Orbitrap/MS: Potential Application for
      Investigation of Model Organism Metabolomes.
AB  - Identifying non-annotated peaks may have a significant impact on the
      understanding of biological systems. In silico methodologies have focused on ESI
      LC/MS/MS for identifying non-annotated MS peaks. In this study, we employed in
      silico methodology to develop an Isotopic Ratio Outlier Analysis (IROA) workflow
      using enhanced mass spectrometric data acquired with the ultra-high resolution GC
      Orbitrap/MS to determine the identity of non-annotated metabolites. The higher
      resolution of the GC-Orbitrap/MS, together with its wide dynamic range, resulted
      in more IROA peak pairs detected, and increased reliability of chemical formulae
      generation (CFG). IROA uses two different 13C-enriched carbon sources (randomized
      95% 12C and 95% 13C) to produce mirror image isotopologue pairs, whose mass
      difference reveals the carbon chain length (n), which aids in the identification
      of endogenous metabolites. Accurate m/z, n, and derivatization information are
      obtained from our GC/MS workflow for unknown metabolite identification, and aids
      in silico methodologies for identifying isomeric and non-annotated metabolites.
      We were able to mine more mass spectral information using the same Saccharomyces
      cerevisiae growth protocol (Qiu et al. Anal. Chem 2016) with the ultra-high
      resolution GC-Orbitrap/MS, using 10% ammonia in methane as the CI reagent gas. We
      identified 244 IROA peaks pairs, which significantly increased IROA detection
      capability compared with our previous report (126 IROA peak pairs using a GC
      TOF/MS machine). For 55 selected metabolites identified from matched IROA CI and
      EI spectra, using the GC-Orbitrap/MS vs. GC-TOF/MS, the average mass deviation
      for GC-Orbitrap/MS was 1.48 ppm, however, the average mass deviation was 32.2 ppm
      for the GC-TOF/MS machine. In summary, the higher resolution and wider dynamic
      range of the GC-Orbitrap/MS enabled more accurate CFG, and the coupling of
      accurate mass GC/MS IROA methodology with in silico fragmentation has great
      potential in unknown metabolite identification, with applications for
      characterizing model organism networks.

PMID- 29346328
TI  - Comparison of SVM, RF and ELM on an Electronic Nose for the Intelligent
      Evaluation of Paraffin Samples.
AB  - Paraffin odor intensity is an important quality indicator when a paraffin
      inspection is performed. Currently, paraffin odor level assessment is mainly
      dependent on an artificial sensory evaluation. In this paper, we developed a
      paraffin odor analysis system to classify and grade four kinds of paraffin
      samples. The original feature set was optimized using Principal Component
      Analysis (PCA) and Partial Least Squares (PLS). Support Vector Machine (SVM),
      Random Forest (RF), and Extreme Learning Machine (ELM) were applied to three
      different feature data sets for classification and level assessment of paraffin.
      For classification, the model based on SVM, with an accuracy rate of 100%, was
      superior to that based on RF, with an accuracy rate of 98.33-100%, and ELM, with
      an accuracy rate of 98.01-100%. For level assessment, the R2 related to the
      training set was above 0.97 and the R2 related to the test set was above 0.87.
      Through comprehensive comparison, the generalization of the model based on ELM
      was superior to those based on SVM and RF. The scoring errors for the three
      models were 0.0016-0.3494, lower than the error of 0.5-1.0 measured by industry
      standard experts, meaning these methods have a higher prediction accuracy for
      scoring paraffin level.

PMID- 29346329
TI  - Anti-Phytopathogenic and Cytotoxic Activities of Crude Extracts and Secondary
      Metabolites of Marine-Derived Fungi.
AB  - Thirty-one isolates belonging to eight genera in seven orders were identified
      from 141 strains that were isolated from several marine plants. Alternaria sp.
      and Fusarium sp. were found to be the predominant fungi. Evaluation of the anti
      phytopathogenic bacterial and fungal activities, as well as the cytotoxicity of
      these 31 extracts, revealed that most of them displayed different levels of
      bioactivities. Due to their interesting bioactivities, two fungal strains
      Fusarium equiseti (P18) and Alternaria sp. (P8)-were selected for chemical
      investigation and compounds 1-4 were obtained. The structure of 1 was elucidated
      by 1D and 2D NMR analysis, as well as high-resolution electrospray ionization
      mass spectroscopy (HRESIMS), and the absolute configuration of its stereogenic
      carbon (C-11) was established by comparison of the experimental and calculated
      electronic circular-dichroism (ECD) spectra. Moreover, alterperylenol (4)
      exhibited antibacterial activity against Clavibacter michiganensis with a minimum
      inhibitory concentration (MIC) of 1.95 MUg/mL, which was 2-fold stronger than
      that of streptomycin sulfate. Additionally, an antibacterial mechanism study
      revealed that 4 caused membrane hyperpolarization without evidence of destruction
      of cell membrane integrity. Furthermore, stemphyperylenol (3) displayed potent
      antifungal activity against Pestallozzia theae and Alternaria brassicicola with
      MIC values equal to those of carbendazim. The cytotoxicity of 1 and 2 against
      human lung carcinoma (A-549), human cervical carcinoma (HeLa), and human hepatoma
      (HepG2) cell lines were also evaluated.

PMID- 29346330
TI  - Formulation of Poloxamers for Drug Delivery.
AB  - Poloxamers, also known as Pluronics(r), are block copolymers of poly(ethylene
      oxide) (PEO) and poly(propylene oxide) (PPO), which have an amphiphilic character
      and useful association and adsorption properties emanating from this. Poloxamers
      find use in many applications that require solubilization or stabilization of
      compounds and also have notable physiological properties, including low toxicity.
      Accordingly, poloxamers serve well as excipients for pharmaceuticals. Current
      challenges facing nanomedicine revolve around the transport of typically water
      insoluble drugs throughout the body, followed by targeted delivery. Judicious
      design of drug delivery systems leads to improved bioavailability, patient
      compliance and therapeutic outcomes. The rich phase behavior (micelles,
      hydrogels, lyotropic liquid crystals, etc.) of poloxamers makes them amenable to
      multiple types of processing and various product forms. In this review, we first
      present the general solution behavior of poloxamers, focusing on their self
      assembly properties. This is followed by a discussion of how the self-assembly
      properties of poloxamers can be leveraged to encapsulate drugs using an array of
      processing techniques including direct solubilization, solvent displacement
      methods, emulsification and preparation of kinetically-frozen nanoparticles.
      Finally, we conclude with a summary and perspective.

PMID- 29346332
TI  - Owners and Veterinary Surgeons in the United Kingdom Disagree about What Should
      Happen during a Small Animal Vaccination Consultation.
AB  - Dog and cat vaccination consultations are a common part of small animal practice
      in the United Kingdom. Few data are available describing what happens during
      those consultations or what participants think about their content. The aim of
      this novel study was to investigate the attitudes of dog and cat owners and
      veterinary surgeons towards the content of small animal vaccination
      consultations. Telephone interviews with veterinary surgeons and pet owners
      captured rich qualitative data. Thematic analysis was performed to identify key
      themes. This study reports the theme describing attitudes towards the content of
      the consultation. Diverse preferences exist for what should be prioritised during
      vaccination consultations, and mismatched expectations may lead to negative
      experiences. Vaccination consultations for puppies and kittens were described to
      have a relatively standardised structure with an educational and preventative
      healthcare focus. In contrast, adult pet vaccination consultations were described
      to focus on current physical health problems with only limited discussion of
      preventative healthcare topics. This first qualitative exploration of UK
      vaccination consultation expectations suggests that the content and consistency
      of adult pet vaccination consultations may not meet the needs or expectations of
      all participants. Redefining preventative healthcare to include all preventable
      conditions may benefit owners, pets and veterinary surgeons, and may help to
      provide a clearer structure for adult pet vaccination consultations. This study
      represents a significant advance our understanding of this consultation type.

PMID- 29346335
TI  - Notes from the Field: Legionellosis Outbreak Associated with a Hotel Aquatics
      Facility - Tennessee, 2017.

PMID- 29346331
TI  - Growth Hormone (GH) and Cardiovascular System.
AB  - This review describes the positive effects of growth hormone (GH) on the
      cardiovascular system. We analyze why the vascular endothelium is a real internal
      secretion gland, whose inflammation is the first step for developing
      atherosclerosis, as well as the mechanisms by which GH acts on vessels improving
      oxidative stress imbalance and endothelial dysfunction. We also report how GH
      acts on coronary arterial disease and heart failure, and on peripheral arterial
      disease, inducing a neovascularization process that finally increases flow in
      ischemic tissues. We include some preliminary data from a trial in which GH or
      placebo is given to elderly people suffering from critical limb ischemia, showing
      some of the benefits of the hormone on plasma markers of inflammation, and the
      safety of GH administration during short periods of time, even in diabetic
      patients. We also analyze how Klotho is strongly related to GH, inducing, after
      being released from the damaged vascular endothelium, the pituitary secretion of
      GH, most likely to repair the injury in the ischemic tissues. We also show how GH
      can help during wound healing by increasing the blood flow and some neurotrophic
      and growth factors. In summary, we postulate that short-term GH administration
      could be useful to treat cardiovascular diseases.

PMID- 29346334
TI  - Effect of Gastrointestinal Bleeding on Gastrointestinal Stromal Tumor Patients: A
      Retrospective Cohort Study.
AB  - BACKGROUND The contemporary risk classification criteria of gastrointestinal
      stromal tumors (GISTs) may still have room to improve. The aim of our research
      was to analyze the impact factors for GIST patients' relapse-free survival (RFS).
      Furthermore, we explore whether gastrointestinal (1) bleeding will be a valuable
      indicator to predict GIST patients' prognosis. MATERIAL AND METHODS R0 resection
      GISTs patients were retrospectively enrolled during an 8-year period at West
      China Hospital of Sichuan University, and all patients' data were from the WCHSU
      GIST database. Of a total of 333 GIST patients, 164 patients had GI bleeding.
      Univariate analysis and Cox regression analysis were used to calculate the
      survival and recurrence rates. RESULTS Compared with non-GI-bleeding patients, GI
      bleeding patients had a shorter relapse-free survival (RFS, P=0.003), but among
      the different risk groups, GI bleeding only affected the RFS rate of the high
      risk group. A Cox regression analysis illustrated that tumor site (P<0.001),
      tumor size (P=0.009), mitotic index (P<0.001), tumor rupture (P<0.001), and GI
      bleeding (P=0.01) were independent indicators for GIST patients' RFS. CONCLUSIONS
      Our study demonstrates that the RFS of GIST patients with GI bleeding was
      significantly shorter than that of non-GI-bleeding patients, and GI bleeding was
      an independent negative factor predicting RFS, while GI bleeding had more
      influence among high-risk patients.

PMID- 29346333
TI  - Platelet Rich Plasma: New Insights for Cutaneous Wound Healing Management.
AB  - The overall increase of chronic degenerative diseases associated with ageing
      makes wound care a tremendous socioeconomic burden. Thus, there is a growing need
      to develop novel wound healing therapies to improve cutaneous wound healing. The
      use of regenerative therapies is becoming increasingly popular due to the low
      invasive procedures needed to apply them. Platelet-rich plasma (PRP) is gaining
      interest due to its potential to stimulate and accelerate the wound healing
      process. The cytokines and growth factors forming PRP play a crucial role in the
      healing process. This article reviews the emerging field of skin wound
      regenerative therapies with particular emphasis on PRP and the role of growth
      factors in the wound healing process.

PMID- 29346336
TI  - Respiratory Syncytial Virus Seasonality - United States, 2014-2017.
AB  - Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract
      infection in young children worldwide (1-3). In the United States, RSV infection
      results in >57,000 hospitalizations and 2 million outpatient visits each year
      among children aged <5 years (3). Recent studies have highlighted the importance
      of RSV in adults as well as children (4). CDC reported RSV seasonality
      nationally, by U.S. Department of Health and Human Services (HHS) regions* and
      for the state of Florida, using a new statistical method that analyzes polymerase
      chain reaction (PCR) laboratory detections reported to the National Respiratory
      and Enteric Virus Surveillance System (NREVSS)
      (https://www.cdc.gov/surveillance/nrevss/index.html). Nationally, across three
      RSV seasons, lasting from the week ending July 5, 2014 through July 1, 2017, the
      median RSV onset occurred at week 41 (mid-October), and lasted 31 weeks until
      week 18 (early May). The median national peak occurred at week 5 (early
      February). Using these new methods, RSV season circulation patterns differed from
      those reported from previous seasons (5). Health care providers and public health
      officials use RSV circulation data to guide diagnostic testing and to time the
      administration of RSV immunoprophylaxis for populations at high risk for severe
      respiratory illness (6). With several vaccines and other immunoprophlyaxis
      products in development, estimates of RSV circulation are also important to the
      design of clinical trials and future vaccine effectiveness studies.

PMID- 29346337
TI  - Notes from the Field: Baylisascaris procyonis Encephalomyelitis in a Toddler -
      King County, Washington, 2017.

PMID- 29346339
TI  - QuickStats: Percentage Distribution* of Adult Day Services Center Participants,
      by Place of Residence? - National Study of Long-Term Care Providers, United
      States, 2016.
AB  - In 2016, 51.5% of adult day services center participants lived in a private
      residence with relative(s), 19.9% lived alone in a private residence, 16.3% lived
      in an assisted living/residential care community, 5.3% lived in a private
      residence with nonrelative(s), 4.5% had another living arrangement, and 1.5%
      lived in a nursing home.

PMID- 29346338
TI  - Current Cigarette Smoking Among Adults - United States, 2016.
AB  - The U.S. Surgeon General has concluded that the burden of death and disease from
      tobacco use in the United States is overwhelmingly caused by cigarettes and other
      combusted tobacco products (1). Cigarettes are the most commonly used tobacco
      product among U.S. adults, and about 480,000 U.S. deaths per year are caused by
      cigarette smoking and secondhand smoke exposure (1). To assess progress toward
      the Healthy People 2020 target of reducing the proportion of U.S. adults aged
      >=18 years who smoke cigarettes to <=12.0% (objective TU-1.1),* CDC analyzed data
      from the 2016 National Health Interview Survey (NHIS). In 2016, the prevalence of
      current cigarette smoking among adults was 15.5%, which was a significant decline
      from 2005 (20.9%); however, no significant change has occurred since 2015
      (15.1%). In 2016, the prevalence of cigarette smoking was higher among adults who
      were male, aged 25-64 years, American Indian/Alaska Native or multiracial, had a
      General Education Development (GED) certificate, lived below the federal poverty
      level, lived in the Midwest or South, were uninsured or insured through Medicaid,
      had a disability/limitation, were lesbian, gay, or bisexual (LGB), or had serious
      psychological distress. During 2005-2016, the percentage of ever smokers who quit
      smoking increased from 50.8% to 59.0%. Proven population-based interventions are
      critical to reducing the health and economic burden of smoking-related diseases
      among U.S. adults, particularly among subpopulations with the highest smoking
      prevalences (1,2).

PMID- 29346341
TI  - Erratum: Vol. 66, No. 50.

PMID- 29346340
TI  - Disparities in Preconception Health Indicators - ?Behavioral Risk Factor
      Surveillance System, 2013-2015, and Pregnancy Risk Assessment Monitoring System,
      2013-2014.
AB  - PROBLEM/CONDITION: Preconception health is a broad term that encompasses the
      overall health of nonpregnant women during their reproductive years (defined here
      as aged 18-44 years). Improvement of both birth outcomes and the woman's health
      occurs when preconception health is optimized. Improving preconception health
      before and between pregnancies is critical for reducing maternal and infant
      mortality and pregnancy-related complications. The National Preconception Health
      and Health Care Initiative's Surveillance and Research work group suggests ten
      prioritized indicators that states can use to monitor programs or activities for
      improving the preconception health status of women of reproductive age. This
      report includes overall and stratified estimates for nine of these preconception
      health indicators. REPORTING PERIOD: 2013-2015. DESCRIPTION OF SYSTEMS: Survey
      data from two surveillance systems are included in this report. The Behavioral
      Risk Factor Surveillance System (BRFSS) is an ongoing state-based, landline and
      cellular telephone survey of noninstitutionalized adults in the United States
      aged >=18 years that is conducted by state and territorial health departments.
      BRFSS is the main source of self-reported data for states on health risk
      behaviors, chronic health conditions, and preventive health services primarily
      related to chronic disease in the United States. The Pregnancy Risk Assessment
      Monitoring System (PRAMS) is an ongoing U.S. state- and population-based
      surveillance system administered collaboratively by CDC and state health
      departments. PRAMS is designed to monitor selected maternal behaviors,
      conditions, and experiences that occur before, during, and shortly after
      pregnancy that are self-reported by women who recently delivered a live-born
      infant. This report summarizes BRFSS and PRAMS data on nine of 10 prioritized
      preconception health indicators (i.e., depression, diabetes, hypertension,
      current cigarette smoking, normal weight, recommended physical activity, recent
      unwanted pregnancy, prepregnancy multivitamin use, and postpartum use of a most
      or moderately effective contraceptive method) for which the most recent data are
      available. BRFSS data from all 50 states and the District of Columbia were used
      for six preconception health indicators: depression, diabetes (excluded if
      occurring only during pregnancy or if limited to borderline/prediabetes
      conditions), hypertension (excluded if occurring only during pregnancy or if
      limited to borderline/prehypertension conditions), current cigarette smoking,
      normal weight, and recommended physical activity. PRAMS data from 30 states, the
      District of Columbia, and New York City were used for three preconception health
      indicators: recent unwanted pregnancy, prepregnancy multivitamin use, and
      postpartum use of a most or moderately effective contraceptive method by women or
      their husbands or partners (i.e., male or female sterilization, hormonal implant,
      intrauterine device, injectable contraceptive, oral contraceptive, hormonal
      patch, or vaginal ring). Heavy alcohol use during the 3 months before pregnancy
      also was included in the prioritized set of 10 indicators, but PRAMS data for
      each reporting area are not available until 2016 for that indicator. Therefore,
      estimates for heavy alcohol use are not included in this report. All BRFSS
      preconception health estimates are based on 2014-2015 data except two
      (hypertension and recommended physical activity are based on 2013 and 2015 data).
      All PRAMS preconception health estimates rely on 2013-2014 data. Prevalence
      estimates of indicators are reported for women aged 18-44 years overall, by age
      group, race-ethnicity, health insurance status, and reporting area. Chi-square
      tests were conducted to assess differences in indicators by age group,
      race/ethnicity, and insurance status. RESULTS: During 2013-2015, prevalence
      estimates of indicators representing risk factors were generally highest and
      prevalence estimates of health-promoting indicators were generally lowest among
      older women (35-44 years), non-Hispanic black women, uninsured women, and those
      residing in southern states. For example, prevalence of ever having been told by
      a health care provider that they had a depressive disorder was highest among
      women aged 35-44 years (23.1%) and lowest among women aged 18-24 years (19.2%).
      Prevalence of postpartum use of a most or moderately effective method of
      contraception was lowest among women aged 35-44 years (50.6%) and highest among
      younger women aged 18-24 years (64.9%). Self-reported prepregnancy multivitamin
      use and getting recommended levels of physical activity were lowest among non
      Hispanic black women (21.6% and 42.8%, respectively) and highest among non
      Hispanic white women (37.8% and 53.8%, respectively). Recent unwanted pregnancy
      was lowest among non-Hispanic white women and highest among non-Hispanic black
      women (5.0% and 11.6%, respectively). All but three indicators (diabetes,
      hypertension, and use of a most or moderately effective contraceptive method)
      varied by insurance status; for instance, prevalence of current cigarette smoking
      was higher among uninsured women (21.0%) compared with insured women (16.1%), and
      prevalence of normal weight was lower among women who were uninsured (38.6%),
      compared with women who were insured (46.1%). By reporting area, the range of
      women reporting ever having been told by a health care provider that they had
      diabetes was 5.0% (Alabama) to 1.9% (Utah), and women reporting ever having been
      told by a health care provider that they had hypertension ranged from 19.2%
      (Mississippi) to 7.0% (Minnesota). INTERPRETATION: Preconception health risk
      factors and health-promoting indicators varied by age group, race/ethnicity,
      insurance status, and reporting area. These disparities highlight subpopulations
      that might benefit most from interventions that improve preconception health.
      PUBLIC HEALTH ACTION: Eliminating disparities in preconception health can
      potentially reduce disparities in two of the leading causes of death in early and
      middle adulthood (i.e., heart disease and diabetes). Public health officials can
      use this information to provide a baseline against which to evaluate state
      efforts to improve preconception health.

PMID- 29346342
TI  - Attention-Deficit/Hyperactivity Disorder Medication Prescription Claims Among
      Privately Insured Women Aged 15-44 Years - United States, 2003-2015.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder
      that affects individuals across the lifespan. ADHD medication use among pregnant
      women is increasing (1), but consensus about the safety of ADHD medication use
      during pregnancy is lacking. Given that nearly half of U.S. pregnancies are
      unintended (2), and early pregnancy is a critical period for fetal development,
      examining trends in ADHD medication prescriptions among reproductive-aged women
      is important to quantify the population at risk for potential exposure. CDC used
      the Truven Health MarketScan Commercial Database* for the period 2003-2015 to
      estimate the percentage of women aged 15-44 years with private employer-sponsored
      insurance who filled prescriptions for ADHD medications each year. The percentage
      of reproductive-aged women who filled at least one ADHD medication prescription
      increased 344% from 2003 (0.9% of women) to 2015 (4.0% of women). In 2015, the
      most frequently filled medications were mixed amphetamine salts,
      lisdexamfetamine, and methylphenidate. Prescribing ADHD medications to
      reproductive-aged women is increasingly common; additional research on ADHD
      medication safety during pregnancy is warranted to inform women and their health
      care providers about any potential risks associated with ADHD medication exposure
      before and during pregnancy.

PMID- 29346343
TI  - Asthma Mortality Among Persons Aged 15-64 Years, by Industry and Occupation -
      United States, 1999-2016.
AB  - In 2015, an estimated 18.4 million U.S. adults had current asthma, and 3,396
      adult asthma deaths were reported (1). An estimated 11%-21% of asthma deaths
      might be attributable to occupational exposures (2). To describe asthma mortality
      among persons aged 15-64 years,* CDC analyzed multiple cause-of-death data? for
      1999-2016 and industry and occupation information collected from 26 statesS for
      the years 1999, 2003, 2004, and 2007-2012. Proportionate mortality ratios (PMRs) 
      for asthma among persons aged 15-64 years were calculated. During 1999-2016, a
      total of 14,296 (42.9%) asthma deaths occurred among males and 19,011 (57.1%)
      occurred among females. Based on an estimate that 11%-21% of asthma deaths might
      be related to occupational exposures, during this 18-year period, 1,573-3,002
      asthma deaths in males and 2,091-3,992 deaths in females might have resulted from
      occupational exposures. Some of these deaths might have been averted by
      instituting measures to prevent potential workplace exposures. The annual age
      adjusted asthma death rate** per 1 million persons aged 15-64 years declined from
      13.59 in 1999 to 9.34 in 2016 (p<0.001) among females, and from 9.14 (1999) to
      7.78 (2016) (p<0.05) among males. The highest significantly elevated asthma PMRs
      for males were for those in the food, beverage, and tobacco products
      manufacturing industry (1.82) and for females were for those in the social
      assistance industry (1.35) and those in community and social services occupations
      (1.46). Elevated asthma mortality among workers in certain industries and
      occupations underscores the importance of optimal asthma management and
      identification and prevention of potential workplace exposures.

PMID- 29346344
TI  - Development of immune and microbial environments is independently regulated in
      the mammary gland.
AB  - Breastfeeding is important for mammals, providing immunological and
      microbiological advantages to neonates, together with the nutritional supply from
      the mother. However, the mechanisms of this functional diversity in the mammary
      gland remain poorly characterized. Here, we show that, similar to the
      gastrointestinal tract, the mammary gland develops immune and microbial
      environments consisting of immunoglobulin A (IgA) and the microflora,
      respectively, both of which are important for protecting neonates and the mother
      from infectious diseases. The IgA production and microflora development are
      coordinated in the gastrointestinal tract but seem to be independently regulated
      in the mammary gland. In particular, the chemokine (C-C motif) ligand 28 and poly
      Ig receptor, crucial molecules for the IgA production in milk, were expressed
      normally in germ-free lactating mice but were almost undetectable in postweaning
      mothers, regardless of the microflora presence. Our findings offer insights into
      potentially improving the quality of breastfeeding, using both immunological and
      microbiological approaches.

PMID- 29346346
TI  - Protein kinase C-delta (PKCdelta), a marker of inflammation and tuberculosis
      disease progression in humans, is important for optimal macrophage killing
      effector functions and survival in mice.
AB  - This corrects the article DOI: 10.1038/mi.2017.68.

PMID- 29346345
TI  - The cytosolic sensor STING is required for intestinal homeostasis and control of
      inflammation.
AB  - STING (stimulator of interferon genes) is a cytosolic sensor for cyclic
      dinucleotides and also an adaptor molecule for intracellular DNA receptors.
      Although STING has important functions in the host defense against pathogens and
      in autoimmune diseases, its physiological relevance in intestinal homeostasis is
      largely unknown. In this study, we show that STING-/- mice presented defective
      protective mechanisms of intestinal mucosa, including decreased number of goblet
      cells, diminished mucus production, and lower levels of secretory IgA, when
      compared with wild-type (WT) mice. Fecal content and microbiota DNA could
      activate STING, indicating a role of this molecule in gut. Microbiota composition
      was altered in STING-/- mice toward a more inflammatory profile, evidencing a
      reduction in the Allobacolum and Bifidobacterium groups along with increase in
      Disulfovibrio bacteria. Absence of STING lead to decrease in induced
      intraepithelial lymphocytes (IEL) and to increase in group 1 innate lymphoid cell
      (ILC1) as well as ILC3 frequencies and decrease in ILC2 in the colon. Development
      and function of Foxp3+ and LAP+ regulatory T cells were also compromised in STING
      /- mice. Moreover, these mice were highly susceptible to dextran sodium sulfate
      induced colitis, T-cell-induced colitis, and enteric Salmonella typhimurium
      infection when compared with WT animals. Therefore, our results identify an
      important role of STING in maintaining gut homeostasis and also a protective
      effect in controlling gut inflammation.

PMID- 29346348
TI  - Macrophages regulate lung ILC2 activation via Pla2g5-dependent mechanisms.
AB  - Group V phospholipase A2 (Pla2g5) is a lipid-generating enzyme necessary for
      macrophage effector functions in pulmonary inflammation. However, the lipid
      mediators involved and their cellular targets have not been identified. Mice
      lacking Pla2g5 showed markedly reduced lung ILC2 activation and eosinophilia
      following repetitive Alternaria Alternata inhalation. While Pla2g5-null mice had
      Wt levels of immediate IL-33 release after one Alternaria dose, they failed to
      upregulate IL-33 in macrophages following repeated Alternaria administration.
      Unexpectedly, while adoptive transfer of bone marrow-derived (BM)-macrophages
      restored ILC2 activation and eosinophilia in Alternaria-exposed Pla2g5-null mice,
      exogenous IL-33 did not. Conversely, transfers of Pla2g5-null BM-macrophages
      reduced inflammation in Alternaria-exposed Wt mice. Mass spectrometry analysis of
      free fatty acids (FFAs) demonstrated significantly reduced FFAs (including
      linoleic acid (LA) and oleic acid (OA)) in lung and BM-macrophages lacking
      Pla2g5. Exogenous administration of LA or LA+OA to Wt mice sharply potentiated IL
      33-induced lung eosinophilia and ILC2 expansion in vitro and in vivo. In
      contrast, OA potentiated IL-33-induced inflammation and ILC2 expansion in Pla2g5
      null mice, but LA was inactive both in vivo and in vitro. Notably, Pla2g5-null
      ILC2s showed significantly reduced expression of the FFA-receptor-1 compared to
      Wt ILC2s. Thus, macrophage-associated Pla2g5 contributes significantly to type-2
      immunity through regulation of IL-33 induction and FFA-driven ILC2 activation.

PMID- 29346347
TI  - CD103+CD11b+ mucosal classical dendritic cells initiate long-term switched
      antibody responses to flagellin.
AB  - Antibody responses induced at mucosal and nonmucosal sites demonstrate a
      significant level of autonomy. Here, we demonstrate a key role for mucosal
      interferon regulatory factor-4 (IRF4)-dependent CD103+CD11b+ (DP), classical
      dendritic cells (cDCs) in the induction of T-dependent immunoglobulin G (IgG) and
      immunoglobulin A (IgA) responses in the mesenteric lymph node (MLN) following
      systemic immunization with soluble flagellin (sFliC). In contrast, IRF8-dependent
      CD103+CD11b- (SP) are not required for these responses. The lack of this response
      correlated with a complete absence of sFliC-specific plasma cells in the MLN,
      small intestinal lamina propria, and surprisingly also the bone marrow (BM). Many
      sFliC-specific plasma cells accumulating in the BM of immunized wild-type mice
      expressed alpha4beta7+, suggesting a mucosal origin. Collectively, these results
      suggest that mucosal DP cDC contribute to the generation of the sFliC-specific
      plasma cell pool in the BM and thus serve as a bridge linking the mucosal and
      systemic immune system.

PMID- 29346349
TI  - Early treatment of SIV+ macaques with an alpha4beta7 mAb alters virus
      distribution and preserves CD4+ T cells in later stages of infection.
AB  - Integrin alpha4beta7 mediates the trafficking of leukocytes, including CD4+ T
      cells, to lymphoid tissues in the gut. Virus mediated damage to the gut is
      implicated in HIV and SIV mediated chronic immune activation and leads to
      irreversible damage to the immune system. We employed an immuno-PET/CT imaging
      technique to evaluate the impact of an anti-integrin alpha4beta7 mAb alone or in
      combination with ART, on the distribution of both SIV infected cells and CD4+
      cells in rhesus macaques infected with SIV. We determined that alpha4beta7 mAb
      reduced viral antigen in an array of tissues of the lung, spleen, axillary, and
      inguinal lymph nodes. These sites are not directly linked to alpha4beta7 mediated
      homing; however, the most pronounced reduction in viral load was observed in the
      colon. Despite this reduction, alpha4beta7 mAb treatment did not prevent an
      apparent depletion of CD4+ T cells in gut in the acute phase of infection that is
      characteristic of HIV/SIV infection. However, alpha4beta7 mAb appeared to
      facilitate the preservation or restoration of CD4+ T cells in gut tissues at
      later stages of infection. Since damage to the gut is believed to play a central
      role in HIV pathogenesis, these results support further evaluation of alpha4beta7
      antagonists in the study and treatment of HIV disease.

PMID- 29346351
TI  - Adolescents and young adults with cancer in New Zealand-understudied and
      underserved.

PMID- 29346352
TI  - Compassion defined: it's time for doctors to step up.

PMID- 29346350
TI  - Epithelial-mesenchymal transition in Crohn's disease.
AB  - Crohn's disease (CD) is often accompanied by the complications of intestinal
      strictures and fistulas. These complications remain obstacles in CD treatment. In
      recent years, the importance of epithelial-mesenchymal transition in the
      pathogenesis of CD-associated fistulas and intestinal fibrosis has become
      apparent. Epithelial-mesenchymal transition refers to a dynamic change, wherein
      epithelial cells lose their polarity and adherence and acquire migratory function
      and fibroblast features. During formation of CD-associated fistulas, intestinal
      epithelial cells dislocate from the basement membrane and migrate to the lining
      of the fistula tracts, where they convert into transitional cells as a
      compensatory response under the insufficient wound healing condition. In CD
      associated intestinal fibrosis, epithelial-mesenchymal transition may serve as a
      source of new fibroblasts and consequently lead to overproduction of
      extracellular matrix. In this review, we present current knowledge of epithelial
      mesenchymal transition and its role in the pathogenesis of CD in order to
      highlight new therapy targets for the associated complications.

PMID- 29346353
TI  - The burden of cancer in 25-29 year olds in New Zealand: a case for a wider
      adolescent and young adult age range?
AB  - AIMS: New Zealand currently defines the adolescent and young adult (AYA) group
      for cancer services as young people 12-24 years of age, while other countries
      favour a designation of 15-29 years. This study was undertaken to compare cancer
      incidence and survival among 25-29 year olds to New Zealand's younger AYA
      population and to assess survival for our 15-29 year population against
      international benchmarks. METHODS: Diagnostic and demographic information for
      cancer registrations between 2000 and 2009 for 25-29 year olds was obtained from
      the New Zealand Cancer Registry. Incidence rates (IR) and five-year relative
      survival estimates were calculated according to AYA diagnostic group/sub-group,
      sex and prioritised ethnicity. RESULTS: 1,541 new primary malignant cancers were
      diagnosed (IR: 588 per million). Five-year relative survival was 85%, but was
      significantly lower for Maori and Pacific peoples (both 77%) compared to non
      Maori/non-Pacific peoples (88%). In the overall 15-29 year AYA cohort, disease
      specific outcomes for bone tumours (46%) and breast cancer (64%) were inferior to
      international standards. CONCLUSION: New Zealand 25 to 29 year olds are at twice
      the risk of developing cancer as those 15-24 years. Given that the survival
      disparities identified were remarkably consistent with those for younger AYA,
      consideration should be given widening New Zealand's AYA age range.

PMID- 29346354
TI  - Compassion from a palliative care perspective.
AB  - BACKGROUND: Compassion is a core virtue in medicine and lies at the heart of good
      medical care. It connects us to each other and reflects our need for
      relationships with others. AIM: Our aim is to explore how palliative care
      patients perceive, understand and experience compassion from health
      professionals, and to inform clinical practice. METHODS: Seven hospice managers
      in the North Island of New Zealand were contacted and invited to join the study.
      Twenty participants expressed a desire to participate and were involved in semi
      structured face-to-face interviews. A set of questions guided the interviewers
      with interviews lasting between 15-60 minutes. RESULTS: In regards to the
      question, what is your understanding of compassion?, four central themes emerged:
      connection, presence and warmth, respect and caring. When asked, what advice can
      you give to trainee health professionals?, participants articulated four themes:
      connecting with patients and talking in a way they can understand, treating the
      person with respect, showing interest in them and being a positive presence for
      them. CONCLUSIONS: Compassion was seen as a connection between the carer and the
      patient. Compassion is having a positive presence and warmth; an attitude of
      respect and caring. The main advice given by research participants to enhance
      compassion is for doctors and nurses to connect, to talk in a way that can be
      understood, and show interest and respect to patients facing the end of their
      lives.

PMID- 29346355
TI  - Increasing rates of people identifying as transgender presenting to Endocrine
      Services in the Wellington region.
AB  - AIMS: Overseas clinics specialising in management of transgender people have
      noted a marked increase in the numbers of people requesting therapy in the last
      few years. No data has been presented for New Zealand. We therefore reviewed the
      number of transgender people seen in the Wellington Endocrine Service to assess
      if the pattern was similar and assess any potential problems for service
      delivery. METHODS: Using hospital records, we reviewed the new appointments of
      people who were referred for advice on gender reassignment and seen in the
      Wellington Endocrine Service from 1990 to 2016. RESULTS: In total, 438 people who
      identified as transgender attended the clinic at least once in this period. There
      has been a progressive increase in number of people identifying as transgender
      presenting to the clinic, particularly since 2010. In addition to increasing
      overall numbers, there has been in particular increase in referrals for people
      under age 30, as well as an increasing proportion of people requesting female-to
      male (FtM) therapy so that it is now approaching the number of people requesting
      male-to-female therapy (MtF). CONCLUSION: The pattern observed is comparable to
      changes reported overseas. These changes have practical consequences for the
      delivery of both secondary and primary level healthcare, requiring an increased
      focus on clinical coordination between the relevant medical services and their
      links to the primary services sector.

PMID- 29346356
TI  - The effect of trampoline parks on presentations to the Christchurch Emergency
      Department.
AB  - AIMS: To analyse trampoline-related injuries suffered after the opening of two
      new trampoline parks in Christchurch. METHODS: Data was collected from three 90
      day periods. All trampoline-related injuries were collected from electronic
      documentation and coding. Those injured after both arenas opened were contacted
      and a semi-structured interview performed. RESULTS: In the 90 days after both
      parks opened there were 602 claims for trampoline-related injuries with 106
      hospital presentations (55% male). This was a significant increase (p<0.01) from
      one year earlier (333 claims, 37 hospital presentations) and the 90 days prior to
      their opening (201 claims, 15 hospital presentations). Most injuries affected an
      older group of children, aged between 10-14 years (26%, n=28), compared to the
      other two periods (p<0.01). There was also a greater proportion of lower-limb
      injuries (52%, n=55) compared to the other two periods (p<0.01). Thirty-six
      required hospital admission, with 29 operations and an average length of stay of
      2.11 days. One trampoline park allowed two or more people to use the same
      trampoline at the same time, and had over twice as many presentations (33%, n=35)
      than the other trampoline park (14%, n=15). CONCLUSIONS: Christchurch saw a
      significant increase in trampoline-related injuries after the opening of two new
      parks. These injuries involved an older group of children, affected predominantly
      the lower limbs and were more severe than those reported from the use of domestic
      trampolines. Consistent with past research, the trampoline park allowing multiple
      users had a higher proportion of presentations and more injuries requiring
      operative intervention.

PMID- 29346357
TI  - Type of cows' milk consumption and relationship to health predictors in New
      Zealand preschool children.
AB  - AIMS: New Zealand dietary guidelines recommend children from two years of age
      consume low- or reduced-fat milk. We aimed to investigate the predictors of type
      of milk consumption in preschool children. METHODS: Data were drawn from a cross
      sectional study which enrolled preschool children (2-<5 years, n=1,329) from
      throughout New Zealand. RESULTS: Cows' milk was consumed regularly by 88% of
      children. Of these, 26% consumed plain low- or reduced-fat milk, while 74%
      consumed full-fat milk. The adjusted odds of consuming plain low- or reduced-fat
      milk were increased in older children: three-year old (OR=1.80, 95% CI 1.29
      2.50); four-year old (OR=1.93, 95% CI 1.38-2.72) versus two-year old children,
      and were decreased in Maori (OR=0.56, 95% CI 0.36-0.88) and Pacific children
      (OR=0.32, 95% CI 0.12-0.86) compared with New Zealand European children.
      Approximately 18% of children were overweight/obese. The odds (adjusted for socio
      demographic characteristics) of consuming plain low- or reduced-fat milk were
      increased in overweight children (OR=1.74, 95% CI 1.20-2.54) than normal weight
      children. CONCLUSIONS: The type of milk consumed by preschool children varies
      with child demographics and anthropometry. Further research is warranted to
      investigate caregivers/parents' knowledge about dietary guidelines and to
      determine the causal relationship between obesity and milk type consumption. The
      findings of the current study may have important implications for developing and
      shaping interventions and in helping shape public health policy and practice to
      promote cows' milk consumption in preschool children.

PMID- 29346359
TI  - A systematic review of leadership training for medical students.
AB  - BACKGROUND: Leadership is increasingly being recognised as an essential
      requirement for doctors. Many medical schools are in the process of developing
      formal leadership training programmes, but it remains to be elucidated what
      characteristics make such programmes effective, and to what extent current
      programmes are effective, beyond merely positive learner reactions. This review's
      objective was to investigate the effectiveness of undergraduate medical
      leadership curricula and to explore common features of effective curricula.
      METHODS: A systematic literature search was conducted. Articles describing and
      evaluating undergraduate medical leadership curricula were included. Outcomes
      were stratified and analysed according to a modified Kirkpatrick's model for
      evaluating educational outcomes. RESULTS: Eleven studies met inclusion criteria.
      Leadership curricula evaluated were markedly heterogeneous in their duration and
      composition. The majority of studies utilised pre- and post- intervention
      questionnaires for evaluation. Two studies described randomised controlled trials
      with objective measures. Outcomes were broadly positive. Only one study reported
      neutral outcomes. CONCLUSIONS: A wide range of leadership curricula have shown
      subjective effectiveness, including short interventions. There is limited
      objective evidence however, and few studies have measured effectiveness at the
      system and patient levels. Further research is needed investigating objective and
      downstream outcomes, and use of standard frameworks for evaluation will
      facilitate effective comparison of initiatives.

PMID- 29346358
TI  - Rates of unsuspected thyroid cancer in multinodular thyroid disease.
AB  - BACKGROUND: Previously the risk of concomitant thyroid cancer in multinodular
      goitre (MNG) has been reported as approximately 4%. Cancer risk in toxic MNG was
      often considered lower than for non-toxic MNG, due to a possible protective
      effect of TSH suppression. However, recent American data suggest an approximately
      18% risk of occult malignancy in both toxic and non-toxic MNG. AIMS: To assess
      malignancy risk in a New Zealand population undergoing thyroidectomy for MNG.
      METHODS: Single-centre study of patients undergoing thyroidectomy for MNG from 1
      December 2006 to 30 November 2016. RESULTS: Six hundred and two patients
      underwent surgery for MNG (448 non-toxic and 154 toxic). Of these, 95/602 (16%)
      had thyroid cancer. After excluding patients operated for preoperative suspicion
      for cancer, 30/401 (8%) patients with non-toxic MNG and 15/151 (10%) with toxic
      MNG had unsuspected or occult thyroid cancer (p=0.358). Patients with toxic MNG
      were less likely to undergo preoperative fine needle aspiration than those with
      non-toxic MNG (34% vs 52%, respectively p=0.0001). Two-thirds of unsuspected
      thyroid cancers were incidental micropapillary carcinomas and unlikely to alter
      survival irrespective of therapy. CONCLUSION: Malignancy rates in MNG are higher
      than historically reported, although most unsuspected cancers are unlikely to
      alter mortality even if diagnosis is delayed.

PMID- 29346360
TI  - Evaluation of the Report on Euthanasia for the New Zealand Medical Association by
      Grant Gillett.

PMID- 29346361
TI  - Publication and authorship challenges experienced by medical students involved in
      biomedical research.

PMID- 29346362
TI  - Research opportunities for medical students: time flies when you're having fun.

PMID- 29346363
TI  - Euthanasia and abortion.

PMID- 29346365
TI  - The ISCB Student Council Internship Program: Expanding computational biology
      capacity worldwide.
AB  - Education and training are two essential ingredients for a successful career. On
      one hand, universities provide students a curriculum for specializing in one's
      field of study, and on the other, internships complement coursework and provide
      invaluable training experience for a fruitful career. Consequently,
      undergraduates and graduates are encouraged to undertake an internship during the
      course of their degree. The opportunity to explore one's research interests in
      the early stages of their education is important for students because it improves
      their skill set and gives their career a boost. In the long term, this helps to
      close the gap between skills and employability among students across the globe
      and balance the research capacity in the field of computational biology. However,
      training opportunities are often scarce for computational biology students,
      particularly for those who reside in less-privileged regions. Aimed at helping
      students develop research and academic skills in computational biology and
      alleviating the divide across countries, the Student Council of the International
      Society for Computational Biology introduced its Internship Program in 2009. The
      Internship Program is committed to providing access to computational biology
      training, especially for students from developing regions, and improving
      competencies in the field. Here, we present how the Internship Program works and
      the impact of the internship opportunities so far, along with the challenges
      associated with this program.

PMID- 29346364
TI  - Mutations in Caenorhabditis elegans neuroligin-like glit-1, the apoptosis pathway
      and the calcium chaperone crt-1 increase dopaminergic neurodegeneration after 6
      OHDA treatment.
AB  - The loss of dopaminergic neurons is a hallmark of Parkinson's disease, the
      aetiology of which is associated with increased levels of oxidative stress. We
      used C. elegans to screen for genes that protect dopaminergic neurons against
      oxidative stress and isolated glit-1 (gliotactin (Drosophila neuroligin-like)
      homologue). Loss of the C. elegans neuroligin-like glit-1 causes increased
      dopaminergic neurodegeneration after treatment with 6-hydroxydopamine (6-OHDA),
      an oxidative-stress inducing drug that is specifically taken up into dopaminergic
      neurons. Furthermore, glit-1 mutants exhibit increased sensitivity to oxidative
      stress induced by H2O2 and paraquat. We provide evidence that GLIT-1 acts in the
      same genetic pathway as the previously identified tetraspanin TSP-17. After
      exposure to 6-OHDA and paraquat, glit-1 and tsp-17 mutants show almost identical,
      non-additive hypersensitivity phenotypes and exhibit highly increased induction
      of oxidative stress reporters. TSP-17 and GLIT-1 are both expressed in
      dopaminergic neurons. In addition, the neuroligin-like GLIT-1 is expressed in
      pharynx, intestine and several unidentified cells in the head. GLIT-1 is
      homologous, but not orthologous to neuroligins, transmembrane proteins required
      for the function of synapses. The Drosophila GLIT-1 homologue Gliotactin in
      contrast is required for epithelial junction formation. We report that GLIT-1
      likely acts in multiple tissues to protect against 6-OHDA, and that the
      epithelial barrier of C. elegans glit-1 mutants does not appear to be
      compromised. We further describe that hyperactivation of the SKN-1 oxidative
      stress response pathway alleviates 6-OHDA-induced neurodegeneration. In addition,
      we find that mutations in the canonical apoptosis pathway and the calcium
      chaperone crt-1 cause increased 6-OHDA-induced dopaminergic neuron loss. In
      summary, we report that the neuroligin-like GLIT-1, the canonical apoptosis
      pathway and the calreticulin CRT-1 are required to prevent 6-OHDA-induced
      dopaminergic neurodegeneration.

PMID- 29346366
TI  - Testing for soil-transmitted helminth transmission elimination: Analysing the
      impact of the sensitivity of different diagnostic tools.
AB  - In recent years, an increased focus has been placed upon the possibility of the
      elimination of soil-transmitted helminth (STH) transmission using various
      interventions including mass drug administration. The primary diagnostic tool
      recommended by the WHO is the detection of STH eggs in stool using the Kato-Katz
      (KK) method. However, detecting infected individuals using this method becomes
      increasingly difficult as the intensity of infection decreases. Newer techniques,
      such as qPCR, have been shown to have greater sensitivity than KK, especially at
      low prevalence. However, the impact of using qPCR on elimination thresholds is
      yet to be investigated. In this paper, we aim to quantify how the sensitivity of
      these two diagnostic tools affects the optimal prevalence threshold at which to
      declare the interruption of transmission with a defined level of confidence. A
      stochastic, individual-based STH transmission model was used in this study to
      simulate the transmission dynamics of Ascaris and hookworm. Data from a Kenyan
      deworming study were used to parameterize the diagnostic model which was based on
      egg detection probabilities. The positive and negative predictive values (PPV and
      NPV) were calculated to assess the quality of any given threshold, with the
      optimal threshold value taken to be that at which both were maximised. The
      threshold prevalence of infection values for declaring elimination of Ascaris
      transmission were 6% and 12% for KK and qPCR respectively. For hookworm, these
      threshold values are lower at 0.5% and 2% respectively. Diagnostic tests with
      greater sensitivity are becoming increasingly important as we approach the
      elimination of STH transmission in some regions of the world. For declaring the
      elimination of transmission, using qPCR to diagnose STH infection results in the
      definition of a higher prevalence, than when KK is used.

PMID- 29346367
TI  - Assessment of serum pharmacokinetics and urinary excretion of albendazole and its
      metabolites in human volunteers.
AB  - BACKGROUND: Soil Transmitted Helminth (STH) infections negatively impact physical
      and mental development in human populations. Current WHO guidelines recommend
      morbidity control of these infections through mass drug administration (MDA)
      using albendazole (ABZ) or mebendazole. Despite major reductions in STH
      associated morbidity globally, not all programs have demonstrated the expected
      impact on prevalence of parasite infections. These therapeutic failures may be
      related to poor programmatic coverage, suboptimal adherence or the exposure of
      parasites to sub-therapeutic drug concentrations. As part of the DeWorm3 project,
      we sought to characterize the serum disposition kinetics and pattern of urinary
      excretion of ABZ and its main metabolites ABZ sulphoxide (ABZSO) and ABZ sulphone
      (ABZSO2) in humans, and the assessment of the duration and optimal time point
      where ABZ and/or its metabolites can be measured in urine as an indirect
      assessment of an individual's adherence to treatment. METHODOLOGY/PRINCIPAL
      FINDINGS: Consecutive venous blood and urine samples were collected from eight
      (8) human volunteers up to 72 h post-ABZ oral administration. ABZ/metabolites
      were quantified by HPLC. The ABZSO metabolite was the main analyte recovered both
      in serum and urine. ABZSO Cmax in serum was 1.20 +/- 0.44 MUg/mL, reached at 4.75
      h post-treatment. In urine, ABZSO Cmax was 3.24 +/- 1.51 MUg/mL reached at 6.50 h
      post-ABZ administration. CONCLUSION/SIGNIFICANCE: Pharmacokinetic data obtained
      for ABZ metabolites in serum and urine, including the recovery of the ABZ
      sulphoxide derivative up to 72 h in both matrixes and the recovery of the amino
      ABZ sulphone metabolite in urine samples, are suggesting the possibility of
      developing a urine based method to assess compliance to ABZ treatment. Such an
      assay may be useful to optimize ABZ use in human patients. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT03192449.

PMID- 29346368
TI  - Mechanical feedback coordinates cell wall expansion and assembly in yeast mating
      morphogenesis.
AB  - The shaping of individual cells requires a tight coordination of cell mechanics
      and growth. However, it is unclear how information about the mechanical state of
      the wall is relayed to the molecular processes building it, thereby enabling the
      coordination of cell wall expansion and assembly during morphogenesis. Combining
      theoretical and experimental approaches, we show that a mechanical feedback
      coordinating cell wall assembly and expansion is essential to sustain mating
      projection growth in budding yeast (Saccharomyces cerevisiae). Our theoretical
      results indicate that the mechanical feedback provided by the Cell Wall Integrity
      pathway, with cell wall stress sensors Wsc1 and Mid2 increasingly activating
      membrane-localized cell wall synthases Fks1/2 upon faster cell wall expansion,
      stabilizes mating projection growth without affecting cell shape. Experimental
      perturbation of the osmotic pressure and cell wall mechanics, as well as
      compromising the mechanical feedback through genetic deletion of the stress
      sensors, leads to cellular phenotypes that support the theoretical predictions.
      Our results indicate that while the existence of mechanical feedback is essential
      to stabilize mating projection growth, the shape and size of the cell are
      insensitive to the feedback.

PMID- 29346369
TI  - The rise of neglected tropical diseases in the "new Texas".
AB  - Within the last five years, the State of Texas has experienced either
      transmission or outbreaks of Ebola, chikungunya, West Nile, and Zika virus
      infections. Autochthonous transmission of neglected parasitic and bacterial
      diseases has also become increasingly reported. The rise of such emerging and
      neglected tropical diseases (NTDs) has not occurred by accident but instead
      reflects rapidly evolving changes and shifts in a "new" Texas beset by modern and
      globalizing forces that include rapid expansions in population together with
      urbanization and human migrations, altered transportation patterns, climate
      change, steeply declining vaccination rates, and a new paradigm of poverty known
      as "blue marble health." Summarized here are the major NTDs now affecting Texas.
      In addition to the vector-borne viral diseases highlighted above, there also is a
      high level of parasitic infections, including Chagas disease, trichomoniasis, and
      possibly leishmaniasis and toxocariasis, as well as typhus-group rickettsiosis, a
      vector-borne bacterial infection. I also highlight some of the key shifts in
      emerging and neglected disease patterns, partly due to an altered and evolving
      economic and ecological landscape in the new Texas, and provide some preliminary
      disease burden estimates for the major prevalent and incident NTDs.

PMID- 29346370
TI  - Structure, function, and control of the human musculoskeletal network.
AB  - The human body is a complex organism, the gross mechanical properties of which
      are enabled by an interconnected musculoskeletal network controlled by the
      nervous system. The nature of musculoskeletal interconnection facilitates
      stability, voluntary movement, and robustness to injury. However, a fundamental
      understanding of this network and its control by neural systems has remained
      elusive. Here we address this gap in knowledge by utilizing medical databases and
      mathematical modeling to reveal the organizational structure, predicted function,
      and neural control of the musculoskeletal system. We constructed a highly
      simplified whole-body musculoskeletal network in which single muscles connect to
      multiple bones via both origin and insertion points. We demonstrated that, using
      this simplified model, a muscle's role in this network could offer a theoretical
      prediction of the susceptibility of surrounding components to secondary injury.
      Finally, we illustrated that sets of muscles cluster into network communities
      that mimic the organization of control modules in primary motor cortex. This
      novel formalism for describing interactions between the muscular and skeletal
      systems serves as a foundation to develop and test therapeutic responses to
      injury, inspiring future advances in clinical treatments.

PMID- 29346371
TI  - Identification of novel leishmanicidal molecules by virtual and biochemical
      screenings targeting Leishmania eukaryotic translation initiation factor 4A.
AB  - Leishmaniases are neglected parasitic diseases in spite of the major burden they
      inflict on public health. The identification of novel drugs and targets
      constitutes a research priority. For that purpose we used Leishmania infantum
      initiation factor 4A (LieIF), an essential translation initiation factor that
      belongs to the DEAD-box proteins family, as a potential drug target. We modeled
      its structure and identified two potential binding sites. A virtual screening of
      a diverse chemical library was performed for both sites. The results were
      analyzed with an in-house version of the Self-Organizing Maps algorithm combined
      with multiple filters, which led to the selection of 305 molecules. Effects of
      these molecules on the ATPase activity of LieIF permitted the identification of a
      promising hit (208) having a half maximal inhibitory concentration (IC50) of 150
      +/- 15 MUM for 1 MUM of protein. Ten chemical analogues of compound 208 were
      identified and two additional inhibitors were selected (20 and 48). These
      compounds inhibited the mammalian eIF4I with IC50 values within the same range.
      All three hits affected the viability of the extra-cellular form of L. infantum
      parasites with IC50 values at low micromolar concentrations. These molecules
      showed non-significant toxicity toward THP-1 macrophages. Furthermore, their anti
      leishmanial activity was validated with experimental assays on L. infantum
      intramacrophage amastigotes showing IC50 values lower than 4.2 MUM. Selected
      compounds exhibited selectivity indexes between 19 to 38, which reflects their
      potential as promising anti-Leishmania molecules.

PMID- 29346372
TI  - Ceramides in tracheal aspirates of preterm infants: Marker for bronchopulmonary
      dysplasia.
AB  - BACKGROUND: In an experimental mouse model we showed that ceramides play a role
      in the pathogenesis of bronchopulmonary dysplasia (BPD) and are a potential
      target for therapeutic intervention. We investigated whether ceramides are
      detectable in tracheal aspirates (TAs) of preterm infants and differ between
      infants with or without BPD. METHODS: Infants born <= 32 weeks of gestational age
      in need of mechanical ventilation in the first week of life were included. TAs
      were obtained directly after intubation and at day 1, 3, 5, 7, and 14. Ceramide
      concentrations were measured by tandem mass spectrometry. At 36 weeks
      postmenstrual age BPD was defined as having had >= 28 days supplemental oxygen.
      RESULTS: 122 infants were included, of which 14 died and 41 developed BPD. All
      infants showed an increase in ceramides after the first day of intubation. The
      ceramide profile differed significantly between preterm infants who did and did
      not develop BPD. However, the ceramide profile had no additional predictive value
      for BPD development over GA at birth, birth weight and total days of mechanical
      ventilation. CONCLUSIONS: Ceramides are measurable in TAs of preterm born infants
      and may be an early marker for BPD development.

PMID- 29346373
TI  - Reconciling Pasteur and Darwin to control infectious diseases.
AB  - The continual emergence of new pathogens and the increased spread of antibiotic
      resistance in bacterial populations remind us that microbes are living entities
      that evolve at rates that impact public health interventions. Following the
      historical thread of the works of Pasteur and Darwin shows how reconciling
      clinical microbiology, ecology, and evolution can be instrumental to
      understanding pathology, developing new therapies, and prolonging the efficiency
      of existing ones.

PMID- 29346374
TI  - Epidemiological investigation into the prevalence of abnormal inter-arm blood
      pressure differences among different ethnicities in Xinjiang, China.
AB  - OBJECTIVES: The prevalence of and risk factors for IAD among different ethnicity
      groups was unknown. Our aim was to investigate the prevalence of and risk factors
      for IAD among Han, Uygur and Kazakh ethnicities in Xinjiang. China. METHODS: In
      total, 14,618 adult participants (7,799 males and 6,819 females) were recruited
      from the Cardiovascular Risk Survey. A 4-stage stratified cluster random sampling
      method was used. The participants' personal information and medical history were
      assessed by questionnaire. IAD was diagnosed by a noninvasive arteriosclerosis
      analyzer. RESULTS: The prevalence of abnormal IAD among the general population
      was 14.3%, with 12.5% in the Han, 14.9% in the Uygur, and 16.4% in the Kazakh
      populations. The prevalence of abnormal IAD among the hypertensive population was
      19.4%, with 17.0% in the Han, 18.1% in the Uygur, and 22.7% in the Kazakh
      populations. The prevalence of abnormal IAD increased with age (all P < 0.01) but
      was not significantly different between the genders (all P> 0.05). Multivariate
      logistic regression analysis showed that age more than 45 years, obesity and
      hypertriglyceridemia were significantly associated with a higher prevalence of
      IAD. There were different risk factors for abnormal IAD in different ethnicities.
      Middle or old age, obesity, ABI and diabetes mellitus were risk factors for the
      Han population, smoking was a risk factor in the Uygur population, and obesity
      and PAD were risk factors in the Kazakh population. CONCLUSION: The prevalence of
      abnormal IAD in the Kazakh participants was higher than that in the Han and Uygur
      populations among both the general population and the hypertensive population in
      Xinjiang, China. The main risk factors of IAD were age, obesity, and triglyceride
      levels. Different ethnicities had different kinds of risk factors for IAD.

PMID- 29346375
TI  - How do we reach the girls and women who are the hardest to reach? Inequitable
      opportunities in reproductive and maternal health care services in armed conflict
      and forced displacement settings in Colombia.
AB  - OBJECTIVES: This paper assesses inequalities in access to reproductive and
      maternal health services among females affected by forced displacement and sexual
      and gender-based violence in conflict settings in Colombia. This was accomplished
      through the following approaches: first, we assessed the gaps and gradients in
      three selected reproductive and maternal health care services. Second, we
      analyzed the patterns of inequalities in reproductive and maternal health care
      services and changes over time. And finally, we identified challenges and
      strategies for reaching girls and women who are the hardest to reach in conflict
      settings, in order to accelerate progress towards universal health coverage and
      to contribute to meeting the Sustainable Development Goals of good health and
      well-being and gender equality by 2030. METHODS: Three types of data were
      required: data about health outcomes (relating to rates of females affected by
      conflict), information about reproductive and maternal health care services to
      provide a social dimension to unmask inequalities (unmet needs in family
      planning, antenatal care and skilled births attendance); and data on the female
      population. Data sources used include the National Information System for Social
      Protection, the National Registry of Victims, the National Administrative
      Department of Statistics, and Demographic Health Survey at three specific time
      points: 2005, 2010 and 2015. We estimated the slope index of inequality to
      express absolute inequality (gaps) and the concentration index to expresses
      relative inequality (gradients), and to understand whether inequality was
      eliminated over time. RESULTS: Our findings show that even though absolute health
      care service-related inequalities dropped over time, relative inequalities
      worsened or remain unchanged. All summary measures still indicated the existence
      of inequalities as well as common patterns. Our findings suggest that there is a
      pattern of marginal exclusion and incremental patterns of inequality in the
      reproductive and maternal health care service provided to female affected by
      armed conflict. CONCLUSIONS: Overall, the effects of conflict continue to
      threaten reproductive and maternal health in Colombia, impeding progress towards
      the realization of universal health care (UHC) and reinforcing already-existing
      inequities. Key messages and steps forward include the need to understand the two
      distinct patterns of inequalities identified in this study in order to prompt
      improved general policy responses. Addressing unmet needs in reproductive and
      maternal health requires supporting gender equality and prioritizing the girls
      and women in regions with the highest rates of victims of armed conflict, with
      the objective of leaving no girl or woman behind. This analysis represents the
      first attempt to analyze coverage-related inequality in reproductive and maternal
      health care services for female affected by armed conflict in Colombia. As the
      World Health Organization and global health systems leaders call for more
      inclusive engagement, this approach may serve as the key to shaping people
      centred health systems. In this particular case, health care facilities must be
      located in close proximity to girls and women in conflict and post-conflict
      settings in order to deliver essential reproductive and maternal health care
      services. Finally, reducing inequalities in opportunities would not only promote
      equity, but also drive sustainable development.

PMID- 29346376
TI  - Evaluating the sustainability, scalability, and replicability of an STH
      transmission interruption intervention: The DeWorm3 implementation science
      protocol.
AB  - Hybrid trials that include both clinical and implementation science outcomes are
      increasingly relevant for public health researchers that aim to rapidly translate
      study findings into evidence-based practice. The DeWorm3 Project is a series of
      hybrid trials testing the feasibility of interrupting the transmission of soil
      transmitted helminths (STH), while conducting implementation science research
      that contextualizes clinical research findings and provides guidance on
      opportunities to optimize delivery of STH interventions. The purpose of DeWorm3
      implementation science studies is to ensure rapid and efficient translation of
      evidence into practice. DeWorm3 will use stakeholder mapping to identify
      individuals who influence or are influenced by school-based or community-wide
      mass drug administration (MDA) for STH and to evaluate network dynamics that may
      affect study outcomes and future policy development. Individual interviews and
      focus groups will generate the qualitative data needed to identify factors that
      shape, contextualize, and explain DeWorm3 trial outputs and outcomes. Structural
      readiness surveys will be used to evaluate the factors that drive health system
      readiness to implement novel interventions, such as community-wide MDA for STH,
      in order to target change management activities and identify opportunities for
      sustaining or scaling the intervention. Process mapping will be used to
      understand what aspects of the intervention are adaptable across heterogeneous
      implementation settings and to identify contextually-relevant modifiable
      bottlenecks that may be addressed to improve the intervention delivery process
      and to achieve intervention outputs. Lastly, intervention costs and incremental
      cost-effectiveness will be evaluated to compare the efficiency of community-wide
      MDA to standard-of-care targeted MDA both over the duration of the trial and over
      a longer elimination time horizon.

PMID- 29346377
TI  - Assessing the feasibility of interrupting the transmission of soil-transmitted
      helminths through mass drug administration: The DeWorm3 cluster randomized trial
      protocol.
AB  - : Current control strategies for soil-transmitted helminths (STH) emphasize
      morbidity control through mass drug administration (MDA) targeting preschool- and
      school-age children, women of childbearing age and adults in certain high-risk
      occupations such as agricultural laborers or miners. This strategy is effective
      at reducing morbidity in those treated but, without massive economic development,
      it is unlikely it will interrupt transmission. MDA will therefore need to
      continue indefinitely to maintain benefit. Mathematical models suggest that
      transmission interruption may be achievable through MDA alone, provided that all
      age groups are targeted with high coverage. The DeWorm3 Project will test the
      feasibility of interrupting STH transmission using biannual MDA targeting all age
      groups. Study sites (population >=80,000) have been identified in Benin, Malawi
      and India. Each site will be divided into 40 clusters, to be randomized 1:1 to
      three years of twice-annual community-wide MDA or standard-of-care MDA, typically
      annual school-based deworming. Community-wide MDA will be delivered door-to-door,
      while standard-of-care MDA will be delivered according to national guidelines.
      The primary outcome is transmission interruption of the STH species present at
      each site, defined as weighted cluster-level prevalence <=2% by quantitative
      polymerase chain reaction (qPCR), 24 months after the final round of MDA.
      Secondary outcomes include the endline prevalence of STH, overall and by species,
      and the endline prevalence of STH among children under five as an indicator of
      incident infections. Secondary analyses will identify cluster-level factors
      associated with transmission interruption. Prevalence will be assessed using qPCR
      of stool samples collected from a random sample of cluster residents at baseline,
      six months after the final round of MDA and 24 months post-MDA. A smaller number
      of individuals in each cluster will be followed with annual sampling to monitor
      trends in prevalence and reinfection throughout the trial. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT03014167.

PMID- 29346378
TI  - Evaluating the impact of a 'virtual clinic' on patient experience, personal and
      provider costs of care in urinary incontinence: A randomised controlled trial.
AB  - OBJECTIVE: To evaluate the impact of using a 'virtual clinic' on patient
      experience and cost in the care of women with urinary incontinence. MATERIALS AND
      METHODS: Women, aged > 18 years referred to a urogynaecology unit were randomised
      to either (1) A Standard Clinic or (2) A Virtual Clinic. Both groups completed a
      validated, web-based interactive, patient-reported outome measure (ePAQ-Pelvic
      Floor), in advance of their appointment followed by either a telephone
      consultation (Virtual Clinic) or face-to-face consultation (Standard Care). The
      primary outcome was the mean 'short-term outcome scale' score on the Patient
      Experience Questionnaire (PEQ). Secondary Outcome Measures included the other
      domains of the PEQ (Communications, Emotions and Barriers), Client Satisfaction
      Questionnaire (CSQ), Short-Form 12 (SF-12), personal, societal and NHS costs.
      RESULTS: 195 women were randomised: 98 received the intervention and 97 received
      standard care. The primary outcome showed a non-significant difference between
      the two study arms. No significant differences were also observed on the CSQ and
      SF-12. However, the intervention group showed significantly higher PEQ domain
      scores for Communications, Emotions and Barriers (including following adjustment
      for age and parity). Whilst standard care was overall more cost-effective, this
      was minimal (L38.04). The virtual clinic also significantly reduced consultation
      time (10.94 minutes, compared with a mean duration of 25.9 minutes respectively)
      and consultation costs compared to usual care (L31.75 versus L72.17
      respectively), thus presenting potential cost-savings in out-patient management.
      CONCLUSIONS: The virtual clinical had no impact on the short-term dimension of
      the PEQ and overall was not as cost-effective as standard care, due to greater
      clinic re-attendances in this group. In the virtual clinic group, consultation
      times were briefer, communication experience was enhanced and personal costs
      lower. For medical conditions of a sensitive or intimate nature, a virtual clinic
      has potential to support patients to communicate with health professionals about
      their condition.

PMID- 29346380
TI  - Rapidly progressive dementia: An eight year (2008-2016) retrospective study.
AB  - BACKGROUND AND PURPOSE: Rapidly progressive dementia (RPD) is an emergency in
      cognitive neurology, defined as cognitive impairment affecting the daily living
      activities developed over less than 1 year. This study investigated the profile
      of patients with rapidly progressive dementia at first presentation. METHODS:
      Retrospective case analysis was done in 187 patients with rapidly progressive
      dementia who presented to the Postgraduate Institute of Medical Education and
      Research, Chandigarh, India from January 2008 to August 2016. Patients were
      divided into three groups: (1) Reversible (treatable) secondary dementia group,
      (2) Prion dementia group (sporadic Creutzfeldt-Jakob disease), (3) Non-prion
      Neurodegenerative and vascular dementias (primary neurodegenerative and vascular
      dementia). Cases presenting with delirium secondary to metabolic, drug induced or
      septic causes and those with signs of meningitis were excluded. RESULTS:
      Secondary reversible causes formed the most common cause for RPD with immune
      mediated encephalitides, neoplastic and infectious disorders as the leading
      causes. The patients in this series had an younger onset of RPD. Infections
      presenting with RPD accounted for the most common cause in our series (39%) with
      SSPE (41%) as the leading cause followed by neurosyphilis (17.9%) and progressive
      multifocal leukoencephalopathy (15.3%). Immune mediated dementias formed the
      second most common (18.1%) etiologic cause for RPD. The neurodegenerative
      dementias were third common cause for RPD in our series. Neoplastic disorders and
      immune mediated presented early (< 6 months) while neurodegenerative disorders
      presented later (> 6 months). CONCLUSIONS: Rapidly progressive dementia is an
      emergency in cognitive neurology with potentially treatable or reversible causes
      that should be sought for diligently.

PMID- 29346379
TI  - A putative lateral flagella of the cystic fibrosis pathogen Burkholderia dolosa
      regulates swimming motility and host cytokine production.
AB  - Burkholderia dolosa caused an outbreak in the cystic fibrosis clinic at Boston
      Children's Hospital and was associated with high mortality in these patients.
      This species is part of a larger complex of opportunistic pathogens known as the
      Burkholderia cepacia complex (Bcc). Compared to other species in the Bcc, B.
      dolosa is highly transmissible; thus understanding its virulence mechanisms is
      important for preventing future outbreaks. The genome of one of the outbreak
      strains, AU0158, revealed a homolog of the lafA gene encoding a putative lateral
      flagellin, which, in other non-Bcc species, is used for movement on solid
      surfaces, attachment to host cells, or movement inside host cells. Here, we
      analyzed the conservation of the lafA gene and protein sequences, which are
      distinct from those of the polar flagella, and found lafA homologs to be present
      in numerous beta-proteobacteria but notably absent from most other Bcc species. A
      lafA deletion mutant in B. dolosa showed a greater swimming motility than wild
      type due to an increase in the number of polar flagella, but did not appear to
      contribute to biofilm formation, host cell invasion, or murine lung colonization
      or persistence over time. However, the lafA gene was important for cytokine
      production in human peripheral blood mononuclear cells, suggesting it may have a
      role in recognition by the human immune response.

PMID- 29346381
TI  - Control of recollection by slow gamma dominating mid-frequency gamma in
      hippocampus CA1.
AB  - Behavior is used to assess memory and cognitive deficits in animals like Fmr1
      null mice that model Fragile X Syndrome, but behavior is a proxy for unknown
      neural events that define cognitive variables like recollection. We identified an
      electrophysiological signature of recollection in mouse dorsal Cornu Ammonis 1
      (CA1) hippocampus. During a shocked-place avoidance task, slow gamma (SG) (30-50
      Hz) dominates mid-frequency gamma (MG) (70-90 Hz) oscillations 2-3 s before
      successful avoidance, but not failures. Wild-type (WT) but not Fmr1-null mice
      rapidly adapt to relocating the shock; concurrently, SG/MG maxima (SGdom)
      decrease in WT but not in cognitively inflexible Fmr1-null mice. During SGdom,
      putative pyramidal cell ensembles represent distant locations; during place
      avoidance, these are avoided places. During shock relocation, WT ensembles
      represent distant locations near the currently correct shock zone, but Fmr1-null
      ensembles represent the formerly correct zone. These findings indicate that
      recollection occurs when CA1 SG dominates MG and that accurate recollection of
      inappropriate memories explains Fmr1-null cognitive inflexibility.

PMID- 29346382
TI  - 6-OHDA-induced dopaminergic neurodegeneration in Caenorhabditis elegans is
      promoted by the engulfment pathway and inhibited by the transthyretin-related
      protein TTR-33.
AB  - Oxidative stress is linked to many pathological conditions including the loss of
      dopaminergic neurons in Parkinson's disease. The vast majority of disease cases
      appear to be caused by a combination of genetic mutations and environmental
      factors. We screened for genes protecting Caenorhabditis elegans dopaminergic
      neurons from oxidative stress induced by the neurotoxin 6-hydroxydopamine (6
      OHDA) and identified the transthyretin-related gene ttr-33. The only described C.
      elegans transthyretin-related protein to date, TTR-52, has been shown to mediate
      corpse engulfment as well as axon repair. We demonstrate that TTR-52 and TTR-33
      have distinct roles. TTR-33 is likely produced in the posterior arcade cells in
      the head of C. elegans larvae and is predicted to be a secreted protein. TTR-33
      protects C. elegans from oxidative stress induced by paraquat or H2O2 at an
      organismal level. The increased oxidative stress sensitivity of ttr-33 mutants is
      alleviated by mutations affecting the KGB-1 MAPK kinase pathway, whereas it is
      enhanced by mutation of the JNK-1 MAPK kinase. Finally, we provide genetic
      evidence that the C. elegans cell corpse engulfment pathway is required for the
      degeneration of dopaminergic neurons after exposure to 6-OHDA. In summary, we
      describe a new neuroprotective mechanism and demonstrate that TTR-33 normally
      functions to protect dopaminergic neurons from oxidative stress-induced
      degeneration, potentially by acting as a secreted sensor or scavenger of
      oxidative stress.

PMID- 29346383
TI  - Seasonally timed treatment programs for Ascaris lumbricoides to increase impact
      An investigation using mathematical models.
AB  - There is clear empirical evidence that environmental conditions can influence
      Ascaris spp. free-living stage development and host reinfection, but the impact
      of these differences on human infections, and interventions to control them, is
      variable. A new model framework reflecting four key stages of the A. lumbricoides
      life cycle, incorporating the effects of rainfall and temperature, is used to
      describe the level of infection in the human population alongside the
      environmental egg dynamics. Using data from South Korea and Nigeria, we conclude
      that settings with extreme fluctuations in rainfall or temperature could exhibit
      strong seasonal transmission patterns that may be partially masked by the
      longevity of A. lumbricoides infections in hosts; we go on to demonstrate how
      seasonally timed mass drug administration (MDA) could impact the outcomes of
      control strategies. For the South Korean setting the results predict a
      comparative decrease of 74.5% in mean worm days (the number of days the average
      individual spend infected with worms across a 12 month period) between the best
      and worst MDA timings after four years of annual treatment. The model found no
      significant seasonal effect on MDA in the Nigerian setting due to a narrower
      annual temperature range and no rainfall dependence. Our results suggest that
      seasonal variation in egg survival and maturation could be exploited to maximise
      the impact of MDA in certain settings.

PMID- 29346384
TI  - Histoplasmosis in Africa: An emerging or a neglected disease?
AB  - Histoplasmosis in Africa has markedly increased since the advent of the HIV/AIDS
      epidemic but is under-recognised. Pulmonary histoplasmosis may be misdiagnosed as
      tuberculosis (TB). In the last six decades (1952-2017), 470 cases of
      histoplasmosis have been reported. HIV-infected patients accounted for 38% (178)
      of the cases. West Africa had the highest number of recorded cases with 179; the
      majority (162 cases) were caused by Histoplasma capsulatum var. dubuosii (Hcd).
      From the Southern African region, 150 cases have been reported, and the majority
      (119) were caused by H. capsulatum var. capsulatum (Hcc). There have been 12
      histoplasmin skin test surveys with rates of 0% to 35% positivity. Most cases of
      Hcd presented as localised lesions in immunocompetent persons; however, it was
      disseminated in AIDS patients. Rapid diagnosis of histoplasmosis in Africa is
      only currently possible using microscopy; antigen testing and PCR are not
      available in most of Africa. Treatment requires amphotericin B and itraconazole,
      both of which are not licensed or available in several parts of Africa.

PMID- 29346385
TI  - Combined effectiveness of anthelmintic chemotherapy and WASH among HIV-infected
      adults.
AB  - INTRODUCTION: Current global helminth control guidelines focus on regular
      deworming of targeted populations for morbidity control. However, water,
      sanitation, and hygiene (WASH) interventions may also be important for reducing
      helminth transmission. We evaluated the impact of different potential helminth
      protective packages on infection prevalence, including repeated treatment with
      albendazole and praziquantel with and without WASH access. METHODOLOGY/PRINCIPAL
      FINDINGS: We conducted a cohort study nested within a randomized trial of empiric
      deworming of HIV-infected adults in Kenya. Helminth infections and infection
      intensity were diagnosed using semi-quantitative real-time PCR. We conducted a
      manual forward stepwise model building approach to identify if there are packages
      of interventions that may be protective against an STH infection of any species
      (combined outcome) and each helminth species individually. We conducted secondary
      analyses using the same approach only amongst individuals with no anthelmintis
      exposure. We used interaction terms to test for potential intervention synergy.
      Approximately 22% of the 701 stool samples provided were helminth-infected, most
      of which were of low to moderate intensity. The odds of infection with any STH
      species were lower for individuals who were treated with albendazole (aOR:0.11,
      95%CI: 0.05, 0.20, p<0.001), adjusting for age and sex. Although most WASH
      conditions demonstrated minimal additional benefit in reducing the probability of
      infection with any STH species, access to safe flooring did appear to offer some
      additional protection (aOR:0.34, 95%CI: 0.20, 0.56, p<0.001). For
      schistosomiasis, only treatment with praziquantel was protective (aOR:0.30 95%CI:
      0.14, 0.60, p = 0.001). Amongst individuals who were not treated with albendazole
      or praziquantel, the most protective intervention package to reduce probability
      of STH infections included safe flooring (aOR:0.34, 95%CI: 0.20, 0.59, p<0.001)
      and latrine access (aOR:0.59, 95%CI: 0.35, 0.99, p = 0.05). Across all species,
      there was no evidence of synergy or antagonism between anthelmintic chemotherapy
      with albendazole or praziquantel and WASH resources. CONCLUSIONS/SIGNIFICANCE:
      Deworming is effective in reducing the probability of helminth infections amongst
      HIV-infected adults. With the exception of safe flooring, WASH offers minimal
      additional benefit. However, WASH does appear to significantly reduce infection
      prevalence in adults who are not treated with chemotherapy. TRIAL REGISTRATION:
      ClinicalTrials.gov, NCT00507221.

PMID- 29346386
TI  - Histological subtypes of mouse mammary tumors reveal conserved relationships to
      human cancers.
AB  - Human breast cancer has been characterized by extensive transcriptional
      heterogeneity, with dominant patterns reflected in the intrinsic subtypes. Mouse
      models of breast cancer also have heterogeneous transcriptomes and we noted that
      specific histological subtypes were associated with particular subsets. We
      hypothesized that unique sets of genes define each tumor histological type across
      mouse models of breast cancer. Using mouse models that contained both gene
      expression data and expert pathologist classification of tumor histology on a
      sample by sample basis, we predicted and validated gene expression signatures for
      Papillary, EMT, Microacinar and other histological subtypes. These signatures
      predict known histological events across murine breast cancer models and identify
      counterparts of mouse mammary tumor types in subtypes of human breast cancer.
      Importantly, the EMT, Adenomyoepithelial, and Solid signatures were predictive of
      clinical events in human breast cancer. In addition, a pan-cancer comparison
      revealed that the histological signatures were active in a variety of human
      cancers such as lung, oral, and esophageal squamous tumors. Finally, the
      differentiation status and transcriptional activity implicit within these
      signatures was identified. These data reveal that within tumor histology groups
      are unique gene expression profiles of differentiation and pathway activity that
      stretch well beyond the transgenic initiating events and that have clear
      applicability to human cancers. As a result, our work provides a predictive
      resource and insights into possible mechanisms that govern tumor heterogeneity.

PMID- 29346387
TI  - Inferring the risk factors behind the geographical spread and transmission of
      Zika in the Americas.
AB  - BACKGROUND: An unprecedented Zika virus epidemic occurred in the Americas during
      2015-2016. The size of the epidemic in conjunction with newly recognized health
      risks associated with the virus attracted significant attention across the
      research community. Our study complements several recent studies which have
      mapped epidemiological elements of Zika, by introducing a newly proposed
      methodology to simultaneously estimate the contribution of various risk factors
      for geographic spread resulting in local transmission and to compute the risk of
      spread (or re-introductions) between each pair of regions. The focus of our
      analysis is on the Americas, where the set of regions includes all countries,
      overseas territories, and the states of the US. METHODOLOGY/PRINCIPAL FINDINGS:
      We present a novel application of the Generalized Inverse Infection Model (GIIM).
      The GIIM model uses real observations from the outbreak and seeks to estimate the
      risk factors driving transmission. The observations are derived from the dates of
      reported local transmission of Zika virus in each region, the network structure
      is defined by the passenger air travel movements between all pairs of regions,
      and the risk factors considered include regional socioeconomic factors, vector
      habitat suitability, travel volumes, and epidemiological data. The GIIM relies on
      a multi-agent based optimization method to estimate the parameters, and utilizes
      a data driven stochastic-dynamic epidemic model for evaluation. As expected, we
      found that mosquito abundance, incidence rate at the origin region, and human
      population density are risk factors for Zika virus transmission and spread.
      Surprisingly, air passenger volume was less impactful, and the most significant
      factor was (a negative relationship with) the regional gross domestic product
      (GDP) per capita. CONCLUSIONS/SIGNIFICANCE: Our model generates country level
      exportation and importation risk profiles over the course of the epidemic and
      provides quantitative estimates for the likelihood of introduced Zika virus
      resulting in local transmission, between all origin-destination travel pairs in
      the Americas. Our findings indicate that local vector control, rather than travel
      restrictions, will be more effective at reducing the risks of Zika virus
      transmission and establishment. Moreover, the inverse relationship between Zika
      virus transmission and GDP suggests that Zika cases are more likely to occur in
      regions where people cannot afford to protect themselves from mosquitoes. The
      modeling framework is not specific for Zika virus, and could easily be employed
      for other vector-borne pathogens with sufficient epidemiological and
      entomological data.

PMID- 29346389
TI  - Rising up: Fertility trends in Egypt before and after the revolution.
AB  - In 2014, Egypt's Demographic and Health Survey (EDHS) documented an increase in
      the total fertility rate (TFR) to 3.5, up from a low of 3.0 recorded by the 2008
      EDHS. The increase has been anecdotally attributed to the social upheaval
      following Egypt's January 2011 revolution, but little is known about when
      fertility first began to increase and among which sub-groups of women. Using
      birth histories from seven rounds of EDHS (1992-2014), this study reconstructed
      fertility rates for single years from 1990-2013 and examined patterns of
      childbearing in five-year birth cohorts of women. We found that the decline in
      fertility reversed in 2007, earlier than postulated, plateaued and then increased
      again in 2013. The increase in TFR coincided with a convergence of fertility
      rates across education levels, and there is evidence of a shift toward
      childbearing at younger ages among more educated women, which may be inflating
      period measures of fertility.

PMID- 29346388
TI  - Safety and pharmacokinetic profile of fixed-dose ivermectin with an innovative
      18mg tablet in healthy adult volunteers.
AB  - : Ivermectin is a pivotal drug for the control of onchocerciasis and lymphatic
      filariasis, which is increasingly identified as a useful drug for the control of
      other Neglected Tropical Diseases. Its role in the treatment of soil transmitted
      helminthiasis through improved efficacy against Trichuris trichiura in
      combination with other anthelmintics might accelerate the progress towards
      breaking transmission. Ivermectin is a derivative of Avermectin B1, and consists
      of an 80:20 mixture of the equipotent homologous 22,23 dehydro B1a and B1b.
      Pharmacokinetic characteristics and safety profile of ivermectin allow to explore
      innovative uses to further expand its utilization through mass drug
      administration campaigns to improve coverage rates. We conducted a phase I
      clinical trial with 54 healthy adult volunteers who sequentially received 2
      experimental treatments using a new 18 mg ivermectin tablet in a fixed-dose
      strategy of 18 and 36 mg single dose regimens, compared to the standard, weight
      based 150-200 MUg/kg, regimen. Volunteers were recruited in 3 groups based on
      body weight. Plasma concentrations of ivermectin were measured through HPLC up to
      168 hours post treatment. Safety data showed no significant differences between
      groups and no serious adverse events: headache was the most frequent adverse
      event in all treatment groups, none of them severe. Pharmacokinetic parameters
      showed a half-life between 81 and 91 h in the different treatment groups. When
      comparing the systemic bioavailability (AUC0t and Cmax) of the reference product
      (WA-ref) with the other two study groups using fixed doses, we observed an
      overall increase in AUC0t and Cmax for the two experimental treatments of 18 mg
      and 36 mg. Body mass index (BMI) and weight were associated with t1/2 and V/F,
      probably reflecting the high liposolubility of IVM with longer retention times
      proportional to the presence of more adipose tissue. Systemic exposure to
      ivermectin (AUC0t or Cmax) was not associated with BMI or weight in our study.
      These findings contribute to further understand the pharmacokinetic
      characteristics of ivermectin, highlighting its safety across different dosing
      regimens. They also correlate with known pharmacokinetic parameters showing
      stable levels of AUC and Cmax across a wide range of body weights, which
      justifies the strategy of fix dosing from a pharmacokinetic perspective. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT03173742.

PMID- 29346390
TI  - Africanized bees extend their distribution in California.
AB  - Africanized honey bees (Apis mellifera) arrived in the western hemisphere in the
      1950s and quickly spread north reaching California in the 1990s. These bees are
      highly defensive and somewhat more difficult to manage for commercial purposes
      than the European honey bees traditionally kept. The arrival of these bees and
      their potentially replacing European bees over much of the state is thus of great
      concern. After a 25 year period of little systematic sampling, a recent small
      scale study found Africanized honey bees in the Bay Area of California, far north
      of their last recorded distribution. The purpose of the present study was to
      expand this study by conducting more intensive sampling of bees from across
      northern California. We found Africanized honey bees as far north as Napa and
      Sacramento. We also found Africanized bees in all counties south of these
      counties. Africanized honey bees were particularly abundant in parts of the
      central valley and Monterey. This work suggests the northern spread of
      Africanized honey bees may not have stopped. They may still be moving north at a
      slow rate, although due to the long gaps in sampling it is currently impossible
      to tell for certain. Future work should routinely monitor the distribution of
      these bees to distinguish between these two possibilities.

PMID- 29346392
TI  - Sequential linear regression with online standardized data.
AB  - The present study addresses the problem of sequential least square
      multidimensional linear regression, particularly in the case of a data stream,
      using a stochastic approximation process. To avoid the phenomenon of numerical
      explosion which can be encountered and to reduce the computing time in order to
      take into account a maximum of arriving data, we propose using a process with
      online standardized data instead of raw data and the use of several observations
      per step or all observations until the current step. Herein, we define and study
      the almost sure convergence of three processes with online standardized data: a
      classical process with a variable step-size and use of a varying number of
      observations per step, an averaged process with a constant step-size and use of a
      varying number of observations per step, and a process with a variable or
      constant step-size and use of all observations until the current step. Their
      convergence is obtained under more general assumptions than classical ones. These
      processes are compared to classical processes on 11 datasets for a fixed total
      number of observations used and thereafter for a fixed processing time. Analyses
      indicate that the third-defined process typically yields the best results.

PMID- 29346391
TI  - Development and validation of a population based risk algorithm for obesity: The
      Obesity Population Risk Tool (OPoRT).
AB  - BACKGROUND: Given the dramatic rise in the prevalence of obesity, greater focus
      on prevention is necessary. We sought to develop and validate a population risk
      tool for obesity to inform prevention efforts. METHODS: We developed the Obesity
      Population Risk Tool (OPoRT) using the longitudinal National Population Health
      Survey and sex-specific Generalized Estimating Equations to predict the 10-year
      risk of obesity among adults 18 and older. The model was validated using a
      bootstrap approach accounting for the survey design. Model performance was
      measured by the Brier statistic, discrimination was measured by the C-statistic,
      and calibration was assessed using the Hosmer-Lemeshow Goodness of Fit Chi Square
      (HL chi2). RESULTS: Predictive factors included baseline body mass index, age,
      time and their interactions, smoking status, living arrangements, education,
      alcohol consumption, physical activity, and ethnicity. OPoRT showed good
      performance for males and females (Brier 0.118 and 0.095, respectively),
      excellent discrimination (C statistic >= 0.89) and achieved calibration (HL chi2
      <20). CONCLUSION: OPoRT is a valid and reliable algorithm that can be applied to
      routinely collected survey data to estimate the risk of obesity and identify
      groups at increased risk of obesity. These results can guide prevention efforts
      aimed at reducing the population burden of obesity.

PMID- 29346393
TI  - Computational study of HIV gp120 as a target for polyanionic entry inhibitors:
      Exploiting the V3 loop region.
AB  - Multiple approaches are being utilized to develop therapeutics to treat HIV
      infection. One approach is designed to inhibit entry of HIV into host cells, with
      a target being the viral envelope glycoprotein, gp120. Polyanionic compounds have
      been shown to be effective in inhibiting HIV entry, with a mechanism involving
      electrostatic interactions with the V3 loop of gp120 being proposed. In this
      study, we applied computational methods to elucidate molecular interactions
      between the repeat unit of the precisely alternating polyanion, Poly(4,4'
      stilbenedicarboxylate-alt-maleic acid) (DCSti-alt-MA) and the V3 loop of gp120
      from strains of HIV against which these polyanions were previously tested (IIIb,
      BaL, 92UG037, JR-CSF) as well as two strains for which gp120 crystal structures
      are available (YU2, 2B4C). Homology modeling was used to create models of the
      gp120 proteins. Using monomers of the gp120 protein, we applied extensive
      molecular dynamics simulations to obtain dominant morphologies that represent a
      variety of open-closed states of the V3 loop to examine the interaction of 112
      ligands of the repeating units of DCSti-alt-MA docked to the V3 loop and
      surrounding residues. Using the distance between the V1/V2 and V3 loops of gp120
      as a metric, we revealed through MD simulations that gp120 from the lab-adapted
      strains (BaL and IIIb), which are more susceptible to inhibition by DCSti-alt-MA,
      clearly transitioned to the closed state in one replicate of each simulation set,
      whereas none of the replicates from the Tier II strains (92UG037 and JR-CSF) did
      so. Docking repeat unit microspecies to the gp120 protein before and after MD
      simulation enabled identification of residues that were key for binding. Notably,
      only a few residues were found to be important for docking both before and after
      MD simulation as a result of the conformational heterogeneity provided by the
      simulations. Consideration of the residues that were consistently involved in
      interactions with the ligand revealed the importance of both hydrophilic and
      hydrophobic moieties of the ligand for effective binding. The results also
      suggest that polymers of DCSti-alt-MA with repeating units of different
      configurations may have advantages for therapeutic efficacy.

PMID- 29346394
TI  - Decision time and confidence predict choosers' identification performance in
      photographic showups.
AB  - In vast contrast to the multitude of lineup studies that report on the link
      between decision time, confidence, and identification accuracy, only a few
      studies looked at these associations for showups, with results varying widely
      across studies. We therefore set out to test the individual and combined value of
      decision time and post-decision confidence for diagnosing the accuracy of
      positive showup decisions using confidence-accuracy characteristic curves and
      Bayesian analyses. Three-hundred-eighty-four participants viewed a stimulus event
      and were subsequently presented with two showups which could be target-present or
      target-absent. As expected, we found a negative decision time-accuracy and a
      positive post-decision confidence-accuracy correlation for showup selections.
      Confidence-accuracy characteristic curves demonstrated the expected additive
      effect of combining both postdictors. Likewise, Bayesian analyses, taking into
      account all possible target-presence base rate values showed that fast and
      confident identification decisions were more diagnostic than slow or less
      confident decisions, with the combination of both being most diagnostic for
      postdicting accurate and inaccurate decisions. The postdictive value of decision
      time and post-decision confidence was higher when the prior probability that the
      suspect is the perpetrator was high compared to when the prior probability that
      the suspect is the perpetrator was low. The frequent use of showups in practice
      emphasizes the importance of these findings for court proceedings. Overall, these
      findings support the idea that courts should have most trust in showup
      identifications that were made fast and confidently, and least in showup
      identifications that were made slowly and with low confidence.

PMID- 29346395
TI  - Evaluation of participatory teaching methods in undergraduate medical students'
      learning along the first academic courses.
AB  - The European Higher Education Area (EHEA) is an opportunity to redesign medical
      education. Academic training is now focused on acquiring not only knowledge, but
      also those competencies critical to face complex professional scenarios. Together
      with re-evaluating traditional teaching methods, EHEA has forced a technological
      shift in the way we teach. By critically assessing the impact of novel teaching
      methodologies, we can better define biomedical education demands. Here, we
      address this question on a sample of medical students instructed in basic
      subjects along the first two academic courses. Two hundred and one medical
      students participated in the study (n = 128 first year, n = 73 second year).
      Quantitative (conventional survey statistics) and qualitative (open coding)
      approaches were combined to analyze data from surveys, confidential
      questionnaires, semi-structured interviews and open discussion. First year
      medical students rated more positively the use of participatory methodologies
      than second year students. A major drawback is detected in the perceived
      workload. Active teaching methodologies show a strong reliance on their time of
      implementation for medical students, a key aspect to be considered in the design
      of integrative participatory curricula along the first academic courses.

PMID- 29346396
TI  - Serum miRNA levels are related to glucose homeostasis and islet autoantibodies in
      children with high risk for type 1 diabetes.
AB  - Micro RNAs (miRNAs) are promising disease biomarkers due to their high stability.
      Their expression in serum is altered in type 1 diabetes, but whether deviations
      exist in individuals with high risk for type 1 diabetes remains unexplored. We
      therefore assessed serum miRNAs in high-risk individuals (n = 21) positive for
      multiple islet autoantibodies, age-matched healthy children (n = 17) and recent
      onset type 1 diabetes patients (n = 8), using Serum/Plasma Focus microRNA PCR
      Panels from Exiqon. The miRNA levels in the high-risk group were similar to
      healthy controls, and no specific miRNA profile was identified for the high-risk
      group. However, serum miRNAs appeared to reflect glycemic status and ongoing
      islet autoimmunity in high-risk individuals, since several miRNAs were associated
      to glucose homeostasis and autoantibody titers. High-risk individuals progressing
      to clinical disease after the sampling could not be clearly distinguished from
      non-progressors, while miRNA expression in the type 1 diabetes group deviated
      significantly from high-risk individuals and healthy controls, perhaps explained
      by major metabolic disturbances around the time of diagnosis.

PMID- 29346397
TI  - Dose enhancement effects of gold nanoparticles specifically targeting RNA in
      breast cancer cells.
AB  - Localization microscopy has shown to be capable of systematic investigations on
      the arrangement and counting of cellular uptake of gold nanoparticles (GNP) with
      nanometer resolution. In this article, we show that the application of specially
      modified RNA targeting gold nanoparticles ("SmartFlares") can result in ring like
      shaped GNP arrangements around the cell nucleus. Transmission electron microscopy
      revealed GNP accumulation in vicinity to the intracellular membrane structures
      including them of the endoplasmatic reticulum. A quantification of the radio
      therapeutic dose enhancement as a proof of principle was conducted with gammaH2AX
      foci analysis: The application of both-SmartFlares and unmodified GNPs-lead to a
      significant dose enhancement with a factor of up to 1.2 times the dose deposition
      compared to non-treated breast cancer cells. This enhancement effect was even
      more pronounced for SmartFlares. Furthermore, it was shown that a magnetic field
      of 1 Tesla simultaneously applied during irradiation has no detectable influence
      on neither the structure nor the dose enhancement dealt by gold nanoparticles.

PMID- 29346398
TI  - Dual function of EDTA with silver nanoparticles for root canal treatment-A novel
      modification.
AB  - The chelating and antimicrobial capacity of a novel modification of 17% EDTA with
      silver nanoparticles (AgNPs) (EDTA-AgNPs) was evaluated in-vitro for root canal
      treatment (RCT). The EDTA-AgNPs solution was characterized by UV-Vis
      spectroscopy, zeta-potential and high-resolution transmission electron microscopy
      (HRTEM). Antimicrobial capacity was evaluated against Candida albicans and
      Staphylococcus aureus in planktonic and biofilm cells by broth macrodilution (24
      h) and XTT assays, (1, 10 and 30 min) respectively. The chelating capacity of
      EDTA-AgNPs was assessed indirectly (smear layer removal) and directly
      (demineralizing effect) in bovine dentin at two silver concentrations, 16 and 512
      MUg/ml at 1 and 10 minutes of exposure time. Smear layer removal was evaluated by
      atomic force microscopy (AFM) and scanning electron microscopy (SEM). The
      demineralizing effect was determined by atomic absorption spectroscopy (AAS),
      microhardness test (MH) and X-ray diffractometer (XRD). Synthesized AgNPs were
      quasi-spherical in shape with an average size of 13.09 +/- 8.05 nm. 17% EDTA
      AgNPs was effective to inhibit C. albicans and S. aureus in planktonic and
      biofilm cultures. The smear layer removal and demineralizing effect were similar
      between 17% EDTA-AgNPs and 17% EDTA treatments. The 17% EDTA-AgNPs solution
      proved to be an effective antimicrobial agent, and has a similar chelating
      capacity to 17% EDTA alone. These in-vitro studies strongly suggest that EDTA
      AgNPs could be used for effective smear layer removal, having an antimicrobial
      effect at the same time during RCT.

PMID- 29346399
TI  - The motivation-based calving facility: Social and cognitive factors influence
      isolation seeking behaviour of Holstein dairy cows at calving.
AB  - In order to improve animal welfare it is recommended that dairy farmers move
      calving cows from the herd to individual pens when calving is imminent. However,
      the practicality of moving cows has proven a challenge and may lead to
      disturbance of the cows rather than easing the process of calving. One solution
      may be to allow the cow to seek isolation prior to calving. This study examined
      whether pre-parturient dairy cows will isolate in an individual calving pen
      placed in a group calving setting and whether a closing gate in this individual
      calving pen will cause more cows to isolate prior to calving. Danish Holstein
      cows (n = 66) were housed in groups of six in a group pen with access to six
      individual calving pens connected to the group area. Cows were trained to use one
      of two isolation opportunities i.e. individual calving pens with functional
      closing gates (n = 35) allowing only one cow access at a time, or individual
      calving pens with permanently open gates allowing free cow traffic between group
      area and individual pen (n = 31). The response variables were calving site,
      calving behaviour and social behaviour. Unexpectedly, a functional gate did not
      facilitate isolation seeking, perhaps because the cows were not able to combine a
      learnt response with the motivation to isolate. Dominant cows had the highest
      chance of calving in an individual calving pen. If an alien calf was present in
      the group pen or any of the individual pens, cows were less likely to calve in an
      individual calving pen. Future studies should allow cows easy access to an
      individual calving pen and explore what motivates pre-parturient cows to seek
      isolation in order to facilitate voluntary use of individual calving pens.

PMID- 29346400
TI  - The mechanisms how heparin affects the tumor cell induced VEGF and chemokine
      release from platelets to attenuate the early metastatic niche formation.
AB  - Metastasis is responsible for the majority of cancer associated fatalities. Tumor
      cells leaving the primary tumor and entering the blood flow immediately interact
      with platelets. Activated platelets contribute in different ways to cancer cell
      survival and proliferation, e.g. in formation of the early metastatic niche by
      release of different growth factors and chemokines. Here we show that a direct
      interaction between platelets and MV3 melanoma or MCF7 breast cancer cells
      induces platelet activation and a VEGF release in citrated plasma that cannot be
      further elevated by the coagulation cascade and generated thrombin. In contrast,
      the release of platelet-derived chemokines CXCL5 and CXCL7 depends on both, a
      thrombin-mediated platelet activation and a direct interaction between tumor
      cells and platelets. Preincubation of platelets with therapeutic concentrations
      of unfractionated heparin reduces the tumor cell initiated VEGF release from
      platelets. In contrast, tumor cell induced CXCL5 and CXCL7 release from platelets
      was not impacted by heparin pretreatment in citrated plasma. In defibrinated,
      recalcified plasma, on the contrary, heparin is able to reduce CXCL5 and CXCL7
      release from platelets by thrombin inhibition. Our data indicate that different
      chemokines and growth factors in diverse platelet granules are released in
      tightly regulated processes by various trigger mechanisms. We show for the first
      time that heparin is able to reduce the mediator release induced by different
      tumor cells both in a contact and coagulation dependent manner.

PMID- 29346401
TI  - CD1d deficiency inhibits the development of abdominal aortic aneurysms in LDL
      receptor deficient mice.
AB  - An abdominal aortic aneurysm (AAA) is a dilatation of the abdominal aorta leading
      to serious complications and mostly to death. AAA development is associated with
      an accumulation of inflammatory cells in the aorta including NKT cells. An
      important factor in promoting the recruitment of these inflammatory cells into
      tissues and thereby contributing to the development of AAA is angiotensin II (Ang
      II). We demonstrate that a deficiency in CD1d dependent NKT cells under
      hyperlipidemic conditions (LDLr-/-CD1d-/- mice) results in a strong decline in
      the severity of angiotensin II induced aneurysm formation when compared with LDLr
      /- mice. In addition, we show that Ang II amplifies the activation of NKT cells
      both in vivo and in vitro. We also provide evidence that type I NKT cells
      contribute to AAA development by inducing the expression of matrix degrading
      enzymes in vSMCs and macrophages, and by cytokine dependently decreasing vSMC
      viability. Altogether, these data prove that CD1d-dependent NKT cells contribute
      to AAA development in the Ang II-mediated aneurysm model by enhancing aortic
      degradation, establishing that therapeutic applications which target NKT cells
      can be a successful way to prevent AAA development.

PMID- 29346402
TI  - Gene regulation in Kluyveromyces marxianus in the context of chromosomes.
AB  - Eukaryotes, including the unicellular eukaryotes such as yeasts, employ multiple
      levels of gene regulation. Regulation of chromatin structure through chromatin
      compaction cascades, and influenced by transcriptional insulators, might play a
      role in the coordinated regulation of genes situated at adjacent loci and
      expressed as a co-regulated cluster. Subtelomeric gene silencing, which has
      previously been described in the yeast Saccharomyces cerevisiae, is an example of
      this phenomenon. Transcription from a common regulatory element located around a
      shared intergenic region is another factor that could coordinate the
      transcription of genes at adjacent loci. Additionally, the presence of DNA
      binding sites for the same transcription factor may coordinate expression of
      multiple genes. Yeasts such as the industrially important Kluyveromyces marxianus
      may also display these modes of regulation, but this has not been explored to
      date. An exploration was done using a complete genome and RNA-seq data from a
      previous study of the transcriptional response to glucose or xylose as the carbon
      source in a defined culture medium, and investigating whether the species
      displays clusters of co-localised differentially expressed genes. Regions of
      possible subtelomeric silencing were evident, but were non-responsive to the
      carbon sources tested here. Additionally, glucose or xylose responsive clusters
      were discovered far from telomeres which contained some of the most significantly
      differentially expressed genes, encoding enzymes involved in the utilisation of
      alternative carbon sources such as the industrially important inulinase gene
      INU1. These clusters contained putative binding sites for the carbon source
      responsive transcription factors Mig1 and Adr1. Additionally, we investigated the
      potential contribution of common intergenic regions in co-regulation. Some
      observations were also made in terms of the evolutionary conservation of these
      clusters among yeast species and the presence of potential transcriptional
      insulators at the periphery of these clusters.

PMID- 29346403
TI  - Prime incision: A minimally invasive approach to breast cancer surgical treatment
      A 2 cohort retrospective comparison with conventional breast conserving surgery.
AB  - The prime incision technique is an oncoplastic surgery aimed to remove both the
      breast tumor and the sentinel lymph node through one incision, thus providing
      better aesthetic results than the conventional breast conservative two incision
      technique. We retrospectively evaluated 2 cohorts of 60 consecutive breast cancer
      patients operated by either conventional breast conservative surgery (N = 26) or
      one incision surgery (N = 34). There were no recurrence or death events observed
      in any group. No difference was seen regarding the incidence of surgical
      complications. In the prime incision group the breast volume removed was
      significantly lower than in the conventional surgery group as well as was the
      surgical time and the number of dissected lymph nodes. Aesthetical results were
      better in the one incision group. Further prospective studies are needed to
      validate the one incision technique as a surgical option for selected early stage
      breast cancer patients.

PMID- 29346404
TI  - Bio-fortification potential of global wild annual lentil core collection.
AB  - Lentil, generally known as poor man's' meat due to its high protein value is also
      a good source of dietary fiber, antioxidants and vitamins along with fast cooking
      characteristics. It could be used globally as a staple food crop to eradicate
      hidden hunger, if this nutritionally rich crop is further enriched with essential
      minerals. This requires identification of essential mineral rich germplasm. So,
      in the present study, a core set of 96 wild accessions extracted from 405 global
      wild annual collections comprising different species was analyzed to determine
      its bio-fortification potential. Impressive variation (mg/100 g) was observed for
      different minerals including Na (30-318), K (138.29-1578), P (37.50-593.75), Ca
      (4.74-188.75), Mg (15-159), Fe (2.82-14.12), Zn (1.29-12.62), Cu (0.5-7.12), Mn
      (1.22-9.99), Mo (1.02-11.89), Ni (0.16-3.49), Pb (0.01-0.58), Cd (0-0.03), Co (0
      0.63) and As (0-0.02). Hierarchical clustering revealed high intra- and inter
      specific variability. Further, correlation study showed positive significant
      association among minerals and between minerals including agro-morphological
      traits. Accessions representation from Turkey and Syria had maximum variability
      for different minerals. Diversity analysis exhibited wide geographical variations
      across gene-pool in core set. Potential use of the identified trait-specific
      genetic resources could be initial genetic material, for genetic base broadening
      and biofortification of cultivated lentil.

PMID- 29346406
TI  - Shea (Vitellaria paradoxa Gaertn C. F.) fruit yield assessment and management by
      farm households in the Atacora district of Benin.
AB  - Vitellaria paradoxa (Gaertn C. F.), or shea tree, remains one of the most
      valuable trees for farmers in the Atacora district of northern Benin, where rural
      communities depend on shea products for both food and income. To optimize
      productivity and management of shea agroforestry systems, or "parklands,"
      accurate and up-to-date data are needed. For this purpose, we monitored120
      fruiting shea trees for two years under three land-use scenarios and different
      soil groups in Atacora, coupled with a farm household survey to elicit
      information on decision making and management practices. To examine the local
      pattern of shea tree productivity and relationships between morphological factors
      and yields, we used a randomized branch sampling method and applied a regression
      analysis to build a shea yield model based on dendrometric, soil and land-use
      variables. We also compared potential shea yields based on farm household socio
      economic characteristics and management practices derived from the survey data.
      Soil and land-use variables were the most important determinants of shea fruit
      yield. In terms of land use, shea trees growing on farmland plots exhibited the
      highest yields (i.e., fruit quantity and mass) while trees growing on Lixisols
      performed better than those of the other soil group. Contrary to our
      expectations, dendrometric parameters had weak relationships with fruit yield
      regardless of land-use and soil group. There is an inter-annual variability in
      fruit yield in both soil groups and land-use type. In addition to observed inter
      annual yield variability, there was a high degree of variability in production
      among individual shea trees. Furthermore, household socioeconomic characteristics
      such as road accessibility, landholding size, and gross annual income influence
      shea fruit yield. The use of fallow areas is an important land management
      practice in the study area that influences both conservation and shea yield.

PMID- 29346405
TI  - Oxytocin alters cell fate selection of rat neural progenitor cells in vitro.
AB  - Synthetic oxytocin (sOT) is widely used during labor, yet little is known about
      its effects on fetal brain development despite evidence that it reaches the fetal
      circulation. Here, we tested the hypothesis that sOT would affect early
      neurodevelopment by investigating its effects on neural progenitor cells (NPC)
      from embryonic day 14 rat pups. NPCs expressed the oxytocin receptor (OXTR),
      which was downregulated by 45% upon prolonged treatment with sOT. Next, we
      examined the effects of sOT on NPC death, apoptosis, proliferation, and
      differentiation using antibodies to NeuN (neurons), Olig2 (oligodendrocytes), and
      GFAP (astrocytes). Treated NPCs were analysed with unbiased high-throughput
      immunocytochemistry. Neither 6 nor 24 h exposure to 100 pM or 100 nM sOT had an
      effect on viability as assessed by PI or CC-3 immunocytochemistry. Similarly, sOT
      had negligible effect on NPC proliferation, except that the overall rate of NPC
      proliferation was higher in the 24 h compared to the 6 h group regardless of sOT
      exposure. The most significant finding was that sOT exposure caused NPCs to
      select a predominantly neuronal lineage, along with a concomitant decrease in
      glial cells. Collectively, our data suggest that perinatal exposure to sOT can
      have neurodevelopmental consequences for the fetus, and support the need for in
      vivo anatomical and behavioral studies in offspring exposed to sOT in utero.

PMID- 29346408
TI  - Long lasting insecticidal bed nets ownership, access and use in a high malaria
      transmission setting before and after a mass distribution campaign in Uganda.
AB  - INTRODUCTION: Uganda is conducting a second mass LLIN distribution campaign and
      Katakwi district recently received LLINs as part of this activity. This study was
      conducted to measure the success of the campaign in this setting, an area of high
      transmission, with the objectives to estimate LLIN ownership, access and use pre
      and post campaign implementation. METHODS: Two identical cross sectional surveys,
      based on the Malaria Indicator Survey methodology, were conducted in three sub
      counties in this district (Kapujan, Magoro and Toroma), six months apart, one
      before and another after the mass distribution campaign. Data on three main LLIN
      indicators including; household LLIN ownership, population with access to an LLIN
      and use were collected using a household and a women's questionnaire identical to
      the Malaria Indicator Survey. RESULTS: A total of 601 and 607 households were
      randomly selected in survey one and two respectively. At baseline, 60.57% (56.53
      64.50) of households owned at least one net for every two persons who stayed in
      the household the night before the survey which significantly increased to 70.35%
      (66.54-73.96) after the campaign (p = 0.001). Similarly, the percentage of the
      household population with access to an LLIN significantly increased from 84.76%
      (82.99-86.52) to 91.57% (90.33-92.81), p = 0.001 and the percentage of household
      population that slept under an LLIN the night before the survey also
      significantly increased from 56.85% (55.06-58.82) to 81.72% (76.75-83.21), p =
      0.001. CONCLUSION: The LLIN mass campaign successfully achieved the national
      target of over eighty-five percent of the population with access to an LLIN in
      this setting, however, universal household coverage and use were fourteen and
      three percent points less than the national target respectively. This is useful
      for malaria programs to consider during the planning of future campaigns by
      tailoring efforts around deficient areas like mechanisms to increase universal
      coverage and behavior change communication.

PMID- 29346407
TI  - Relaxin reverses inflammatory and immune signals in aged hearts.
AB  - BACKGROUND: 'Healthy' aging drives structural and functional changes in the heart
      including maladaptive electrical remodeling, fibrosis and inflammation, which
      lower the threshold for cardiovascular diseases such as heart failure (HF) and
      atrial fibrillation (AF). Despite mixed results in recent clinical trials,
      Relaxin-therapy for 2-days could reduce mortality by 37% at 180-days post
      treatment, in patients with acute decompensated HF. Relaxin's short life-span
      (hours) but long-lasting protective actions led us to test the hypothesis that
      relaxin acts at a genomic level to reverse maladaptive remodeling in aging and
      HF. METHODS AND RESULTS: Young (9-month) and aged (24-month), male and female F
      344/Brown Norway rats were treated with relaxin (0.4 mg/kg/day) for 2-weeks
      delivered by subcutaneous osmotic mini-pumps or with sodium acetate (controls).
      The genomic effects of aging and relaxin were evaluated by extracting RNA from
      the left ventricles and analyzing genomic changes by RNA-sequencing, Ingenuity
      Pathway Analysis, MetaCore and tissue immunohistochemistry. We found that aging
      promotes a native inflammatory response with distinct sex-differences and relaxin
      suppresses transcription of multiple genes and signaling pathways associated with
      inflammation and HF in both genders. In addition, aging significantly increased:
      macrophage infiltration and atrial natriuretic peptide levels in female
      ventricles, and activation of the complement cascade, whereas relaxin reversed
      these age-related effects. CONCLUSION: These data support the hypothesis that
      relaxin alters gene transcription and suppresses inflammatory pathways and genes
      associated with HF and aging. Relaxin's suppression of inflammation and fibrosis
      supports its potential as a therapy for cardiovascular and inflammation-related
      diseases, such as HF, AF and diabetes.

PMID- 29346410
TI  - An evaluation of multi-probe locality sensitive hashing for computing
      similarities over web-scale query logs.
AB  - Many modern applications of AI such as web search, mobile browsing, image
      processing, and natural language processing rely on finding similar items from a
      large database of complex objects. Due to the very large scale of data involved
      (e.g., users' queries from commercial search engines), computing such near or
      nearest neighbors is a non-trivial task, as the computational cost grows
      significantly with the number of items. To address this challenge, we adopt
      Locality Sensitive Hashing (a.k.a, LSH) methods and evaluate four variants in a
      distributed computing environment (specifically, Hadoop). We identify several
      optimizations which improve performance, suitable for deployment in very large
      scale settings. The experimental results demonstrate our variants of LSH achieve
      the robust performance with better recall compared with "vanilla" LSH, even when
      using the same amount of space.

PMID- 29346409
TI  - Prediction of absolute risk of acute graft-versus-host disease following
      hematopoietic cell transplantation.
AB  - Allogeneic hematopoietic cell transplantation (HCT) is the treatment of choice
      for a variety of hematologic malignancies and disorders. Unfortunately, acute
      graft-versus-host disease (GVHD) is a frequent complication of HCT. While
      substantial research has identified clinical, genetic and proteomic risk factors
      for acute GVHD, few studies have sought to develop risk prediction tools that
      quantify absolute risk. Such tools would be useful for: optimizing donor
      selection; guiding GVHD prophylaxis, post-transplant treatment and monitoring
      strategies; and, recruitment of patients into clinical trials. Using data on
      9,651 patients who underwent first allogeneic HLA-identical sibling or unrelated
      donor HCT between 01/1999-12/2011 for treatment of a hematologic malignancy, we
      developed and evaluated a suite of risk prediction tools for: (i) acute GVHD
      within 100 days post-transplant and (ii) a composite endpoint of acute GVHD or
      death within 100 days post-transplant. We considered two sets of inputs: (i)
      clinical factors that are typically readily-available, included as main effects;
      and, (ii) main effects combined with a selection of a priori specified two-way
      interactions. To build the prediction tools we used the super learner, a recently
      developed ensemble learning statistical framework that combines results from
      multiple other algorithms/methods to construct a single, optimal prediction tool.
      Across the final super learner prediction tools, the area-under-the curve (AUC)
      ranged from 0.613-0.640. Improving the performance of risk prediction tools will
      likely require extension beyond clinical factors to include biological variables
      such as genetic and proteomic biomarkers, although the measurement of these
      factors may currently not be practical in standard clinical settings.

PMID- 29346411
TI  - Evaluation of Hirst-type spore traps in outdoor Aspergillaceae monitoring during
      large demolition work in hospital.
AB  - Demolition can generate fungal spore suspensions in association with various
      adverse health effects, such as high risk of invasive aspergillosis in
      immunocompromised patients. One block of Edouard Herriot Hospital was entirely
      demolished. The aim of the present study was to evaluate Hirst-type spore traps
      utility in monitoring outdoor Aspergillaceae (Aspergillus spp. + Penicillium
      spp.) spores in part of Edouard Herriot Hospital (Lyon, France) undergoing major
      demolition. Three periods were scheduled in 2015: (A) Gutting of building and
      asbestos removal, (B) Demolition of floors, (C) Excavation and earthwork. Outdoor
      Aspergillaceae fungal load was monitored by cultivable (Air Ideal(r), bioMerieux)
      and non-cultivable methods (Lanzoni VPPS-2000, Analyzair(r), Bologna, Italy).
      Differences of Aspergillaceae recorded with Hirst-type spore traps were observed
      between Gerland and Edouard Herriot Hospital. Differences between Aspergillaceae
      were recorded between day time and night time at Gerland and Edouard Herriot
      Hospital. Daily paired differences between Aspergillaceae recorded with non
      cultivable methodology at Edouard Herriot Hospital and in an area without
      demolition work were significant in Period A vs Period B (p = 10-4) and Period A
      vs Period C (p = 10-4). Weak correlation of daily Aspergillaceae recorded by both
      methods at Edouard Herriot Hospital was significant only for Period C (r = 0.26,
      p = 0.048, n = 58). Meteorological parameters and type of demolition works were
      found to heavily influenced Aspergillaceae dispersion. Non-cultivable methodology
      is a promising tool for outdoor Aspergillaceae scrutiny during major demolition
      work in hospital, helping infection control staff to rapidly implement control
      measures.

PMID- 29346412
TI  - A comparative analysis of preservation techniques for the optimal molecular
      detection of hookworm DNA in a human fecal specimen.
AB  - BACKGROUND: Proper collection and storage of fecal samples is necessary to
      guarantee the subsequent reliability of DNA-based soil-transmitted helminth
      diagnostic procedures. Previous research has examined various methods to preserve
      fecal samples for subsequent microscopic analysis or for subsequent determination
      of overall DNA yields obtained following DNA extraction. However, only limited
      research has focused on the preservation of soil-transmitted helminth DNA in
      stool samples stored at ambient temperature or maintained in a cold chain for
      extended periods of time. METHODOLOGY: Quantitative real-time PCR was used in
      this study as a measure of the effectiveness of seven commercially available
      products to preserve hookworm DNA over time and at different temperatures.
      Results were compared against "no preservative" controls and the "gold standard"
      of rapidly freezing samples at -20 degrees C. The preservation methods were
      compared at both 4 degrees C and at simulated tropical ambient temperature (32
      degrees C) over a period of 60 days. Evaluation of the effectiveness of each
      preservative was based on quantitative real-time PCR detection of target hookworm
      DNA. CONCLUSIONS: At 4 degrees C there were no significant differences in DNA
      amplification efficiency (as measured by Cq values) regardless of the
      preservation method utilized over the 60-day period. At 32 degrees C,
      preservation with FTA cards, potassium dichromate, and a silica bead two-step
      desiccation process proved most advantageous for minimizing Cq value increases,
      while RNA later, 95% ethanol and Paxgene also demonstrate some protective effect.
      These results suggest that fecal samples spiked with known concentrations of
      hookworm-derived egg material can remain at 4 degrees C for 60 days in the
      absence of preservative, without significant degradation of the DNA target.
      Likewise, a variety of preservation methods can provide a measure of protection
      in the absence of a cold chain. As a result, other factors, such as preservative
      toxicity, inhibitor resistance, preservative cost, shipping requirements, sample
      infectivity, and labor costs should be considered when deciding upon an
      appropriate method for the storage of fecal specimens for subsequent PCR
      analysis. Balancing logistical factors and the need to preserve the target DNA,
      we believe that under most circumstances 95% ethanol provides the most pragmatic
      choice for preserving stool samples in the field.

PMID- 29346413
TI  - Genetic diversity and potential routes of transmission of Mycobacterium bovis in
      Mozambique.
AB  - Bovine tuberculosis is a zoonotic disease with largely unknown impact in Africa,
      with risk factors such as HIV and direct contact with animals or consumption of
      Mycobacterium bovis infected animal products. In order to understand and quantify
      this risk and design intervention strategies, good epidemiological studies are
      needed. Such studies can include molecular typing of M. bovis isolates. The aim
      of this study was to apply these tools to provide novel information concerning
      the distribution of bovine tuberculosis in cattle in Mozambique and thereby
      provide relevant information to guide policy development and strategies to
      contain the disease in livestock, and reduce the risk associated with
      transmission to humans. A collection of 178 M. bovis isolates was obtained from
      cattle in Mozambique. Using spoligotyping and regions of difference analysis, we
      classified the isolates into clonal complexes, thus reporting the first
      characterisation of M. bovis strains in this region. Data from MIRU-VNTR typing
      was used to compare isolates from a number of African countries, revealing a
      deeply geographically structured diversity of M. bovis. Eastern Africa appears to
      show high diversity, suggesting deep evolution in that region. The diversity of
      M. bovis in Africa does not seem to be a function of recent importation of
      animals, but is probably maintained within each particular region by constant
      reinfection from reservoir animals. Understanding the transmission routes of M.
      bovis in Mozambique and elsewhere is essential in order to focus public health
      and veterinary resources to contain bovine tuberculosis.

PMID- 29346414
TI  - Reliability of plasma polar metabolite concentrations in a large-scale cohort
      study using capillary electrophoresis-mass spectrometry.
AB  - BACKGROUND: Cohort studies with metabolomics data are becoming more widespread,
      however, large-scale studies involving 10,000s of participants are still limited,
      especially in Asian populations. Therefore, we started the Tsuruoka Metabolomics
      Cohort Study enrolling 11,002 community-dwelling adults in Japan, and using
      capillary electrophoresis-mass spectrometry (CE-MS) and liquid chromatography
      mass spectrometry. The CE-MS method is highly amenable to absolute quantification
      of polar metabolites, however, its reliability for large-scale measurement is
      unclear. The aim of this study is to examine reproducibility and validity of
      large-scale CE-MS measurements. In addition, the study presents absolute
      concentrations of polar metabolites in human plasma, which can be used in future
      as reference ranges in a Japanese population. METHODS: Metabolomic profiling of
      8,413 fasting plasma samples were completed using CE-MS, and 94 polar metabolites
      were structurally identified and quantified. Quality control (QC) samples were
      injected every ten samples and assessed throughout the analysis. Inter- and intra
      batch coefficients of variation of QC and participant samples, and technical
      intraclass correlation coefficients were estimated. Passing-Bablok regression of
      plasma concentrations by CE-MS on serum concentrations by standard clinical
      chemistry assays was conducted for creatinine and uric acid. RESULTS AND
      CONCLUSIONS: In QC samples, coefficient of variation was less than 20% for 64
      metabolites, and less than 30% for 80 metabolites out of the 94 metabolites.
      Inter-batch coefficient of variation was less than 20% for 81 metabolites.
      Estimated technical intraclass correlation coefficient was above 0.75 for 67
      metabolites. The slope of Passing-Bablok regression was estimated as 0.97 (95%
      confidence interval: 0.95, 0.98) for creatinine and 0.95 (0.92, 0.96) for uric
      acid. Compared to published data from other large cohort measurement platforms,
      reproducibility of metabolites common to the platforms was similar to or better
      than in the other studies. These results show that our CE-MS platform is suitable
      for conducting large-scale epidemiological studies.

PMID- 29346415
TI  - Acute multi-sgRNA knockdown of KEOPS complex genes reproduces the microcephaly
      phenotype of the stable knockout zebrafish model.
AB  - Until recently, morpholino oligonucleotides have been widely employed in
      zebrafish as an acute and efficient loss-of-function assay. However, off-target
      effects and reproducibility issues when compared to stable knockout lines have
      compromised their further use. Here we employed an acute CRISPR/Cas approach
      using multiple single guide RNAs targeting simultaneously different positions in
      two exemplar genes (osgep or tprkb) to increase the likelihood of generating
      mutations on both alleles in the injected F0 generation and to achieve a similar
      effect as morpholinos but with the reproducibility of stable lines. This multi
      single guide RNA approach resulted in median likelihoods for at least one
      mutation on each allele of >99% and sgRNA specific insertion/deletion profiles as
      revealed by deep-sequencing. Immunoblot showed a significant reduction for Osgep
      and Tprkb proteins. For both genes, the acute multi-sgRNA knockout recapitulated
      the microcephaly phenotype and reduction in survival that we observed previously
      in stable knockout lines, though milder in the acute multi-sgRNA knockout.
      Finally, we quantify the degree of mutagenesis by deep sequencing, and provide a
      mathematical model to quantitate the chance for a biallelic loss-of-function
      mutation. Our findings can be generalized to acute and stable CRISPR/Cas
      targeting for any zebrafish gene of interest.

PMID- 29346416
TI  - Decoding the network of Trypanosoma brucei proteins that determines sensitivity
      to apolipoprotein-L1.
AB  - In contrast to Trypanosoma brucei gambiense and T. b. rhodesiense (the causative
      agents of human African trypanosomiasis), T. b. brucei is lysed by apolipoprotein
      L1 (apoL1)-containing human serum trypanolytic factors (TLF), rendering it non
      infectious to humans. While the mechanisms of TLF1 uptake, apoL1 membrane
      integration, and T. b. gambiense and T. b. rhodesiense apoL1-resistance have been
      extensively characterised, our understanding of the range of factors that drive
      apoL1 action in T. b. brucei is limited. Selecting our bloodstream-form T. b.
      brucei RNAi library with recombinant apoL1 identified an array of factors that
      supports the trypanocidal action of apoL1, including six putative ubiquitin
      modifiers and several proteins putatively involved in membrane trafficking; we
      also identified the known apoL1 sensitivity determinants, TbKIFC1 and the V
      ATPase. Most prominent amongst the novel apoL1 sensitivity determinants was a
      putative ubiquitin ligase. Intriguingly, while loss of this ubiquitin ligase
      reduces parasite sensitivity to apoL1, its loss enhances parasite sensitivity to
      TLF1-dominated normal human serum, indicating that free and TLF1-bound apoL1 have
      contrasting modes-of-action. Indeed, loss of the known human serum sensitivity
      determinants, p67 (lysosomal associated membrane protein) and the cathepsin-L
      regulator, 'inhibitor of cysteine peptidase', had no effect on sensitivity to
      free apoL1. Our findings highlight a complex network of proteins that influences
      apoL1 action, with implications for our understanding of the anti-trypanosomal
      action of human serum.

PMID- 29346417
TI  - Xylose donor transport is critical for fungal virulence.
AB  - Cryptococcus neoformans, an AIDS-defining opportunistic pathogen, is the leading
      cause of fungal meningitis worldwide and is responsible for hundreds of thousands
      of deaths annually. Cryptococcal glycans are required for fungal survival in the
      host and for pathogenesis. Most glycans are made in the secretory pathway,
      although the activated precursors for their synthesis, nucleotide sugars, are
      made primarily in the cytosol. Nucleotide sugar transporters are membrane
      proteins that solve this topological problem, by exchanging nucleotide sugars for
      the corresponding nucleoside phosphates. The major virulence factor of C.
      neoformans is an anti-phagocytic polysaccharide capsule that is displayed on the
      cell surface; capsule polysaccharides are also shed from the cell and impede the
      host immune response. Xylose, a neutral monosaccharide that is absent from model
      yeast, is a significant capsule component. Here we show that Uxt1 and Uxt2 are
      both transporters specific for the xylose donor, UDP-xylose, although they
      exhibit distinct subcellular localization, expression patterns, and kinetic
      parameters. Both proteins also transport the galactofuranose donor, UDP
      galactofuranose. We further show that Uxt1 and Uxt2 are required for xylose
      incorporation into capsule and protein; they are also necessary for C. neoformans
      to cause disease in mice, although surprisingly not for fungal viability in the
      context of infection. These findings provide a starting point for deciphering the
      substrate specificity of an important class of transporters, elucidate a
      synthetic pathway that may be productively targeted for therapy, and contribute
      to our understanding of fundamental glycobiology.

PMID- 29346418
TI  - The relationship of lung function with ambient temperature.
AB  - BACKGROUND: Lung function is complex trait with both genetic and environmental
      factors contributing to variation. It is unknown how geographic factors such as
      climate affect population respiratory health. OBJECTIVE: To determine whether
      ambient air temperature is associated with lung function (FEV1) in the general
      population. DESIGN/SETTING: Associations between spirometry data from two
      National Health and Nutrition Examination Survey (NHANES) periods representative
      of the U.S. non-institutionalized population and mean annual ambient temperature
      were assessed using survey-weighted multivariate regression.
      PARTICIPANTS/MEASUREMENTS: The NHANES III (1988-94) cohort included 14,088
      individuals (55.6% female) and the NHANES 2007-12 cohort included 14,036
      individuals (52.3% female), with mean ages of 37.4+/-23.4 and 34.4+/-21.8 years
      old and FEV1 percent predicted values of 99.8+/-15.8% and 99.2+/-14.5%,
      respectively. RESULTS: After adjustment for confounders, warmer ambient
      temperatures were associated with lower lung function in both cohorts (NHANES III
      p = 0.020; NHANES 2007-2012 p = 0.014). The effect was similar in both cohorts
      with a 0.71% and 0.59% predicted FEV1 decrease for every 10 degrees F increase in
      mean temperature in the NHANES III and NHANES 2007-2012 cohorts, respectively.
      This corresponds to ~2 percent predicted difference in FEV1 between the warmest
      and coldest regions in the continental United States. CONCLUSIONS: In the general
      U.S. population, residing in regions with warmer ambient air temperatures was
      associated with lower lung function with an effect size similar to that of
      traffic pollution. Rising temperatures associated with climate change could have
      effects on pulmonary function in the general population.

PMID- 29346419
TI  - SAXS analysis of a soluble cytosolic NgBR construct including extracellular and
      transmembrane domains.
AB  - The Nogo-B receptor (NgBR) is involved in oncogenic Ras signaling through
      directly binding to farnesylated Ras. It recruits farnesylated Ras to the non
      lipid-raft membrane for interaction with downstream effectors. However, the
      cytosolic domain of NgBR itself is only partially folded. The lack of several
      conserved secondary structural elements makes this domain unlikely to form a
      complete farnesyl binding pocket. We find that inclusion of the extracellular and
      transmembrane domains that contain additional conserved residues to the cytosolic
      region results in a well folded protein with a similar size and shape to the
      E.coli cis-isoprenyl transferase (UPPs). Small Angle X-ray Scattering (SAXS)
      analysis reveals the radius of gyration (Rg) of our NgBR construct to be 18.2 A
      with a maximum particle dimension (Dmax) of 61.0 A. Ab initio shape modeling
      returns a globular molecular envelope with an estimated molecular weight of 23.0
      kD closely correlated with the calculated molecular weight. Both Kratky plot and
      pair distribution function of NgBR scattering reveal a bell shaped peak which is
      characteristic of a single globularly folded protein. In addition, circular
      dichroism (CD) analysis reveals that our construct has the secondary structure
      contents similar to the UPPs. However, this result does not agree with the
      currently accepted topological orientation of NgBR which might partition this
      construct into three separate domains. This discrepancy suggests another possible
      NgBR topology and lends insight into a potential molecular basis of how NgBR
      facilitates farnesylated Ras recruitment.

PMID- 29346420
TI  - Initial acquisition and succession of the cystic fibrosis lung microbiome is
      associated with disease progression in infants and preschool children.
AB  - The cystic fibrosis (CF) lung microbiome has been studied in children and adults;
      however, little is known about its relationship to early disease progression. To
      better understand the relationship between the lung microbiome and early
      respiratory disease, we characterized the lower airways microbiome using
      bronchoalveolar lavage (BAL) samples obtained from clinically stable CF infants
      and preschoolers who underwent bronchoscopy and chest computed tomography (CT).
      Cross-sectional samples suggested a progression of the lower airways microbiome
      with age, beginning with relatively sterile airways in infancy. By age two,
      bacterial sequences typically associated with the oral cavity dominated lower
      airways samples in many CF subjects. The presence of an oral-like lower airways
      microbiome correlated with a significant increase in bacterial density and
      inflammation. These early changes occurred in many patients, despite the use of
      antibiotic prophylaxis in our cohort during the first two years of life. The
      majority of CF subjects older than four harbored a pathogen dominated airway
      microbiome, which was associated with a further increase in inflammation and the
      onset of structural lung disease, despite a negligible increase in bacterial
      density compared to younger patients with an oral-like airway microbiome. Our
      findings suggest that changes within the CF lower airways microbiome occur during
      the first years of life and that distinct microbial signatures are associated
      with the progression of early CF lung disease.

PMID- 29346421
TI  - The absence of specific yeast heat-shock proteins leads to abnormal aggregation
      and compromised autophagic clearance of mutant Huntingtin proteins.
AB  - The functionality of a protein depends on its correct folding, but newly
      synthesized proteins are susceptible to aberrant folding and aggregation. Heat
      shock proteins (HSPs) function as molecular chaperones that aid in protein
      folding and the degradation of misfolded proteins. Trinucleotide (CAG) repeat
      expansion in the Huntingtin gene (HTT) results in the expression of misfolded
      Huntingtin protein (Htt), which contributes to the development of Huntington's
      disease. We previously found that the degradation of mutated Htt with polyQ
      expansion (Htt103QP) depends on both ubiquitin proteasome system and autophagy.
      However, the role of heat shock proteins in the clearance of mutated Htt remains
      poorly understood. Here, we report that cytosolic Hsp70 (Ssa family), its
      nucleotide exchange factors (Sse1 and Fes1), and a Hsp40 co-chaperone (Ydj1) are
      required for inclusion body formation of Htt103QP proteins and their clearance
      via autophagy. Extended induction of Htt103QP-GFP leads to the formation of a
      single inclusion body in wild-type yeast cells, but mutant cells lacking these
      HSPs exhibit increased number of Htt103QP aggregates. Most notably, we detected
      more aggregated forms of Htt103QP in sse1Delta mutant cells using an agarose gel
      assay. Increased protein aggregates are also observed in these HSP mutants even
      in the absence Htt103QP overexpression. Importantly, these HSPs are required for
      autophagy-mediated Htt103QP clearance, but are less critical for proteasome
      dependent degradation. These findings suggest a chaperone network that
      facilitates inclusion body formation of misfolded proteins and the subsequent
      autophagic clearance.

PMID- 29346422
TI  - Nanoparticle effect on neutrophil produced myeloperoxidase.
AB  - Nanoparticles affect the immune system as they may interact directly with immune
      cells and activate them. However, it is possible that nanoparticles also interact
      with released cytokines and immunologically active enzymes. To test this
      hypothesis, the activity of myeloperoxidase released from activated neutrophils
      was measured in the presence of nanoparticles with different chemistry and size.
      In high concentrations of nanoparticles, myeloperoxidase activity is decreased
      whereas in low concentrations of nanoparticles the activity is increased. The
      effect of the nanoparticles on myeloperoxidase is dependent on the total protein
      concentration as low concentrations of bovine serum albumin together with
      nanoparticles further increase the myeloperoxidase activity. The results herein
      show that nanoparticles affect the immune response not only at the cellular level
      but also on released immune effectors. In particular, they show that the
      nanoparticle effect on myeloperoxidase activity in the neutrophil degranulation
      environment is the result of an intricate interplay between the enzyme and
      protein concentrations in the environment and the available surface area on the
      nanoparticle.

PMID- 29346423
TI  - The association of estimated salt intake with blood pressure in a Viet Nam
      national survey.
AB  - OBJECTIVE: To evaluate the association of salt consumption with blood pressure in
      Viet Nam, a developing country with a high level of salt consumption. DESIGN AND
      SETTING: Analysis of a nationally representative sample of Vietnamese adults 25
      65 years of age who were surveyed using the World Health Organization STEPwise
      approach to Surveillance protocol. Participants who reported acute illness,
      pregnancy, or current use of antihypertensive medications were excluded. Daily
      salt consumption was estimated from fasting mid-morning spot urine samples.
      Associations of salt consumption with systolic blood pressure and prevalent
      hypertension were assessed using adjusted linear and generalized linear models.
      Interaction terms were tested to assess differences by age, smoking, alcohol
      consumption, and rural/urban status. RESULTS: The analysis included 2,333
      participants (mean age: 37 years, 46% male, 33% urban). The average estimated
      salt consumption was 10g/day. No associations of salt consumption with blood
      pressure or prevalent hypertension were observed at a national scale in men or
      women. The associations did not differ in subgroups defined by age, smoking, or
      alcohol consumption; however, associations differed between urban and rural
      participants (p-value for interaction of urban/rural status with salt
      consumption, p = 0.02), suggesting that higher salt consumption may be associated
      with higher systolic blood pressure in urban residents but lower systolic blood
      pressure in rural residents. CONCLUSIONS: Although there was no evidence of an
      association at a national level, associations of salt consumption with blood
      pressure differed between urban and rural residents in Viet Nam. The reasons for
      this differential association are not clear, and given the large rate of rural to
      urban migration experienced in Viet Nam, this topic warrants further
      investigation.

PMID- 29346424
TI  - Higher sequence diversity in the vaginal tract than in blood at early HIV-1
      infection.
AB  - In the majority of cases, human immunodeficiency virus type 1 (HIV-1) infection
      is transmitted through sexual intercourse. A single founder virus in the blood of
      the newly infected donor emerges from a genetic bottleneck, while in rarer
      instances multiple viruses are responsible for systemic infection. We sought to
      characterize the sequence diversity at early infection, between two distinct
      anatomical sites; the female reproductive tract vs. systemic compartment. We
      recruited 72 women from Uganda and Zimbabwe within seven months of HIV-1
      infection. Using next generation deep sequencing, we analyzed the total genetic
      diversity within the C2-V3-C3 envelope region of HIV-1 isolated from the female
      genital tract at early infection and compared this to the diversity of HIV-1 in
      plasma. We then compared intra-patient viral diversity in matched cervical and
      blood samples with three or seven months post infection. Genetic analysis of the
      C2-V3-C3 region of HIV-1 env revealed that early HIV-1 isolates within blood
      displayed a more homogeneous genotype (mean 1.67 clones, range 1-5 clones) than
      clones in the female genital tract (mean 5.7 clones, range 3-10 clones)
      (p<0.0001). The higher env diversity observed within the genital tract compared
      to plasma was independent of HIV-1 subtype (A, C and D). Our analysis of early
      mucosal infections in women revealed high HIV-1 diversity in the vaginal tract
      but few transmitted clones in the blood. These novel in vivo finding suggest a
      possible mucosal sieve effect, leading to the establishment of a homogenous
      systemic infection.

PMID- 29346425
TI  - Hippocampal corticotropin-releasing hormone neurons support recognition memory
      and modulate hippocampal excitability.
AB  - Corticotropin-releasing hormone (CRH) signaling in the hippocampus has been
      established to be important for mediating the effects of stress on learning and
      memory. Given our laboratory's recent characterization of a subset of hippocampal
      CRH neurons as a novel class of GABAergic interneurons, we hypothesized that
      these local GABAergic hippocampal CRH neurons may influence hippocampal function.
      Here we applied an array of molecular tools to selectively label and manipulate
      hippocampal CRH neurons in mice, in order to assess this interneuron population's
      impact on hippocampus-dependent behaviors and hippocampal network excitability.
      Genetically-targeted ablation of hippocampal CRH neurons in vivo impaired object
      recognition memory and substantially enhanced the severity of kainic acid-induced
      seizures. Conversely, selective activation of CRH neurons in vitro suppressed the
      excitability of the mossy fiber-CA3 pathway. Additional experiments are needed to
      reconcile the functions of GABA and CRH signaling of hippocampal CRH neurons on
      hippocampal function. However, our results indicate that this interneuron
      population plays an important role in maintaining adaptive network excitability,
      and provide a specific circuit-level mechanism for this role.

PMID- 29346428
TI  - Revisiting facial resemblance in couples.
AB  - It is widely believed that couples look alike. Consistently, previous research
      reported higher facial similarity for couples than non-couples, and that facial
      similarity predicts marital satisfaction. However, it is unclear if facial
      similarity in couples shown in previous studies was solely driven by extrinsic
      features like hairstyle, glasses, etc. Also unclear is what attributes are
      perceived as similar from the faces of a couple. In three experiments, we showed
      that faces were considered more similar in couples than non-couples even without
      extrinsic features. Personality and age perceived from faces were also more
      similar in couples. Importantly, by matching pairs of faces according to their
      perceived personality, we found that a higher similarity in the perceived
      personality of a face pair led to higher facial similarity and couple likelihood
      ratings. These findings suggest that, instead of a result of pure physical
      analyses, facial similarity in couples is partly based on active social cognitive
      judgments on perceived personality, which may reveal the actual personality of
      the couples and thus inform relationship quality.

PMID- 29346427
TI  - Soluble factors from adipose tissue-derived mesenchymal stem cells promote canine
      hepatocellular carcinoma cell proliferation and invasion.
AB  - The potential effects of adipose tissue-derived mesenchymal stem cells (AT-MSCs)
      on the growth and invasion of canine tumours including hepatocellular carcinoma
      (HCC) are not yet understood. Moreover in humans, the functional contribution of
      AT-MSCs to malignancies remains controversial. The purpose of this study was to
      investigate the effects of AT-MSCs on the proliferation and invasion of canine
      HCC cells in vitro. The effect of AT-MSCs on mRNA levels of factors related to
      HCC progression were also evaluated. Conditioned medium from AT-MSCs (AT-MSC-CM)
      significantly enhanced canine HCC cell proliferation and invasion. Moreover, mRNA
      expression levels of transforming growth factor-beta 1, epidermal growth factor
      A, hepatocyte growth factor, platelet-derived growth factor-beta, vascular
      endothelial growth factor, and insulin-like growth factor 2 were 2.3 +/- 0.4, 2.0
      +/- 0.5, 5.7 +/- 1.9, 1.7 +/- 0.2, 2.1 +/- 0.4, and 1.4 +/- 0.3 times higher,
      respectively (P < 0.05). The mRNA expression level of MMP-2 also increased (to
      4.0 +/- 1.2 times control levels) in canine HCC cells co-cultured with AT-MSCs,
      but MMP-9 mRNA significantly decreased (to 0.5 +/- 0.1 times control levels).
      These findings suggest that soluble factors from AT-MSCs promote the
      proliferation and invasion of canine HCC cells.

PMID- 29346426
TI  - Proliferation and survival of human amniotic epithelial cells during their
      hepatic differentiation.
AB  - Stem cells derived from placental tissues are an attractive source of cells for
      regenerative medicine. Amniotic epithelial cells isolated from human amnion
      (hAECs) have desirable and competitive characteristics that make them stand out
      between other stem cells. They have the ability to differentiate toward all three
      germ layers, they are not tumorigenic and they have immunosuppressive properties.
      Although liver transplantation is the best way to treat acute and chronic hepatic
      failure patients, there are several obstacles. Recently, stem cells have been
      spotlighted as alternative source of hepatocytes because of their potential for
      hepatogenic differentiation. In this work, we aimed to study the proliferation
      and survival of the hAECs during their hepatic differentiation. We have also
      analyzed the changes in pluripotency and hepatic markers. We differentiated
      amniotic cells applying a specific hepatic differentiation (HD) protocol. We
      determined by qRT-PCR that hAECs express significant levels of SOX-2, OCT-4 and
      NANOG during at least 15 days in culture and these pluripotent markers diminish
      during HD. SSEA-4 expression was reduced during HD, measured by
      immunofluorescence. Morphological characteristics became more similar to hepatic
      ones in differentiated cells and representative hepatic markers significantly
      augmented their expression, measured by qRT-PCR and Western blot. Cells achieved
      a differentiation efficiency of 75%. We observed that HD induced proliferation
      and promoted survival of hAECs, during 30 days in culture, evaluated by 3H
      thymidine incorporation and MTT assay. HD also promoted changes in hAECs cell
      cycle. Cyclin D1 expression increased, while p21 and p53 levels were reduced.
      Immunofluorescence analysis showed that Ki-67 expression was upregulated during
      HD. Finally, ERK 1/2 phosphorylation, which is intimately linked to proliferation
      and cell survival, augmented during all HD process and the inhibition of this
      signaling pathway affected not only proliferation but also differentiation. Our
      results suggest that HD promotes proliferation and survival of hAECs, providing
      important evidence about the mechanisms governing their hepatic differentiation.
      We bring new knowledge concerning some of the optimal transplantation conditions
      for these hepatic like cells.

PMID- 29346429
TI  - The farnesoid X receptor agonist obeticholic acid upregulates biliary excretion
      of asymmetric dimethylarginine via MATE-1 during hepatic ischemia/reperfusion
      injury.
AB  - BACKGROUND: We previously showed that increased asymmetric dimethylarginine
      (ADMA) biliary excretion occurs during hepatic ischemia/reperfusion (I/R),
      prompting us to study the effects of the farnesoid X receptor (FXR) agonist
      obeticholic acid (OCA) on bile, serum and tissue levels of ADMA after I/R.
      MATERIAL AND METHODS: Male Wistar rats were orally administered 10mg/kg/day of
      OCA or vehicle for 5 days and were subjected to 60 min partial hepatic ischemia
      or sham-operated. After a 60 min reperfusion, serum, tissue and bile ADMA levels,
      liver mRNA and protein expression of ADMA transporters (CAT-1, CAT-2A, CAT-2B,
      OCT-1, MATE-1), and enzymes involved in ADMA synthesis (protein-arginine-N
      methyltransferase-1, PRMT-1) and metabolism (dimethylarginine
      dimethylaminohydrolase-1, DDAH-1) were measured. RESULTS: OCA administration
      induced a further increase in biliary ADMA levels both in sham and I/R groups,
      with no significant changes in hepatic ADMA content. A reduction in CAT-1, CAT-2A
      or CAT-2B transcripts was found in OCA-treated sham-operated rats compared with
      vehicle. Conversely, OCA administration did not change CAT-1, CAT-2A or CAT-2B
      expression, already reduced by I/R. However, a marked decrease in OCT-1 and
      increase in MATE-1 expression was observed. A similar trend occurred with protein
      expression. CONCLUSION: The reduced mRNA expression of hepatic CAT transporters
      suggests that the increase in serum ADMA levels is probably due to decreased
      liver uptake of ADMA from the systemic circulation. Conversely, the mechanism
      involved in further increasing biliary ADMA levels in sham and I/R groups treated
      with OCA appears to be MATE-1-dependent.

PMID- 29346430
TI  - Estimation of inhalation flow profile using audio-based methods to assess inhaler
      medication adherence.
AB  - Asthma and chronic obstructive pulmonary disease (COPD) patients are required to
      inhale forcefully and deeply to receive medication when using a dry powder
      inhaler (DPI). There is a clinical need to objectively monitor the inhalation
      flow profile of DPIs in order to remotely monitor patient inhalation technique.
      Audio-based methods have been previously employed to accurately estimate flow
      parameters such as the peak inspiratory flow rate of inhalations, however, these
      methods required multiple calibration inhalation audio recordings. In this study,
      an audio-based method is presented that accurately estimates inhalation flow
      profile using only one calibration inhalation audio recording. Twenty healthy
      participants were asked to perform 15 inhalations through a placebo ElliptaTM DPI
      at a range of inspiratory flow rates. Inhalation flow signals were recorded using
      a pneumotachograph spirometer while inhalation audio signals were recorded
      simultaneously using the Inhaler Compliance Assessment device attached to the
      inhaler. The acoustic (amplitude) envelope was estimated from each inhalation
      audio signal. Using only one recording, linear and power law regression models
      were employed to determine which model best described the relationship between
      the inhalation acoustic envelope and flow signal. Each model was then employed to
      estimate the flow signals of the remaining 14 inhalation audio recordings. This
      process repeated until each of the 15 recordings were employed to calibrate
      single models while testing on the remaining 14 recordings. It was observed that
      power law models generated the highest average flow estimation accuracy across
      all participants (90.89+/-0.9% for power law models and 76.63+/-2.38% for linear
      models). The method also generated sufficient accuracy in estimating inhalation
      parameters such as peak inspiratory flow rate and inspiratory capacity within the
      presence of noise. Estimating inhaler inhalation flow profiles using audio based
      methods may be clinically beneficial for inhaler technique training and the
      remote monitoring of patient adherence.

PMID- 29346431
TI  - Sensitivity and specificity of two dried blood spot methods for HIV-1 viral load
      monitoring among patients in Hanoi, Vietnam.
AB  - The use of dried blood spot (DBS) specimens for HIV viral load (VL) monitoring is
      recommended to support the roll-out of routine VL monitoring in low and middle
      income countries (LMICs). To better understand the use of DBS for VL monitoring,
      we evaluated two DBS testing methods, Roche TaqMan(r) Free Virus Evolution
      protocol (DBS-FVE) and Roche TaqMan(r) SPEX protocol (DBS-SPEX)) in patients
      receiving ART at an HIV clinic in Hanoi, Vietnam. Sensitivity, specificity,
      positive predictive value (PPV), and negative predictive value (NPV) were
      calculated for each DBS testing method at the thresholds of 1000 and 5000
      copies/ml compared to plasma VL. At a threshold of 1000 copies/ml, sensitivity,
      specificity, PPV and NPV of the DBS-SPEX method were 98.8% (95% CI: 93.3%-100%),
      74.3% (95% CI: 70.8%-77.5%), 31.5% (95% CI: 25.8%-37.6%), and 99.8% (95% CI:
      98.9%-100%), respectively. Increasing the VL threshold value to 5000 copies/ml
      improved specificity (97.9% CI: 96.6%-98.9%) and PPV (83.9% CI: 74.5%-90.9%).
      Using the DBS-FVE method, at the threshold of 1000 copies/ml and with a
      correction factor of +0.3 log copies/ml, sensitivity was 95.1% (87.8%-98.6%) and
      specificity was 98.8% (97.7%-99.5%). Sensitivity decreased at the threshold of
      5000 copies/ml (65.8%, 95% CI: 54.3%-76.1%). With a correction factor of +0.7 log
      copies/ml, the sensitivity was 96.3% (89.6%-99.2%) and specificity was 98.2%
      (96.9%-99.1%) at the threshold of 1000 copies/ml. We found that the Roche DBS-FVE
      method, with a +0.7 log copies/ml correction factor, performed well with
      sensitivity and specificity greater than 96% at a VL threshold of 1000 copies/m.
      These findings add to the growing body of evidence supporting the use of DBS VL
      testing for ART monitoring. Future research should evaluate the association
      between VL results by DBS and clinical outcome measures such as HIV drug
      resistance, morbidity, and mortality.

PMID- 29346432
TI  - Retraction: Virulent Diuraphis noxia Aphids Over-Express Calcium Signaling
      Proteins to Overcome Defenses of Aphid-Resistant Wheat Plants.

PMID- 29346433
TI  - Vault RNAs partially induces drug resistance of human tumor cells MCF-7 by
      binding to the RNA/DNA-binding protein PSF and inducing oncogene GAGE6.
AB  - BACKGROUND: Vault is the largest nonicosahedral cytosolic nucleoprotein particle,
      which is widely involved in induction of chemoresistance and lead to failure in
      long-term chemotherapy. Vault contains three different major vault proteins
      (MVPs) and four vault RNAs paralogues (vtRNAs, vtRNA1-1, vtRNA1-2, vtRNA1-3 and
      vtRNA2-1). Disruption of the MVPs do not induce hypersensitivity while expression
      of vtRNAs contributes to cells' drug resistance, indicates that vtRNAs, but not
      MVPs play an important role in causing drug resistance. Polypyrimidine tract
      binding protein associated splicing factor (PSF) contributes to cell sensitivity
      to chemotherapy by its transcriptional activity, promotes us to figure out its
      potential association with vtRNAs. METHODS: We investigate the interaction
      between PSF and vtRNAs by electrophoretic mobility shift assays (EMSA) and RNA
      immunoprecipitation (IP), and showed the binding between PSF and vtRNAs.
      Chromatin Immunoprecipitation (ChIP) was performed to detect the effects of
      vtRNAs on the interaction of PSF with GAGE6 promoter. The role of vtRNAs on
      chemoresistance in MCF-7 was detected by CCK-8 and EdU staining. The independent
      role of vtRNAs with MVP is detected by MVP or vtRNAs knockdown. RESULTS: The
      complex with vtRNA1-1 releases PSF, allowing transcription of GAGE6 to proceed.
      Then we showed that induction of GAGE6 caused drug resistance by promoting cell
      proliferation and colony formation in soft agar. Ectopic expression of shRNA
      targets to vtRNA1-1 further confirmed the role of vtRNA1-1 in regulating PSF
      transcriptional activity independent with the expression of MVP. By vtRNA1-1 or
      MVP knockdown, it is revealed that vtRNA1-1 caused chemoresistance independent of
      MVP. Furthermore, knockdown of GAGE6 does not cause drug resistance, indicates
      the GAGE6 is directly involved in cell proliferation, but not the drug
      resistance. CONCLUSION: These results suggest that vtRNAs regulates cell
      proliferation, drug resistance, and possibly other physiological processes of
      humans, by complex formation with PSF.

PMID- 29346434
TI  - Cognitive distortions and gambling near-misses in Internet Gaming Disorder: A
      preliminary study.
AB  - Increased cognitive distortions (i.e. biased processing of chance, probability
      and skill) are a key psychopathological process in disordered gambling. The
      present study investigated state and trait aspects of cognitive distortions in 22
      individuals with Internet Gaming Disorder (IGD) and 22 healthy controls.
      Participants completed the Gambling Related Cognitions Scale as a trait measure
      of cognitive distortions, and played a slot machine task delivering wins, near
      misses and full-misses. Ratings of pleasure ("liking") and motivation to play
      ("wanting") were taken following the different outcomes, and gambling persistence
      was measured after a mandatory phase. IGD was associated with elevated trait
      cognitive distortions, in particular skill-oriented cognitions. On the slot
      machine task, the IGD group showed increased "wanting" ratings compared with
      control participants, while the two groups did not differ regarding their
      "liking" of the game. The IGD group displayed increased persistence on the slot
      machine task. Near-miss outcomes did not elicit stronger motivation to play
      compared to full-miss outcomes overall, and there was no group difference on this
      measure. However, a near-miss position effect was observed, such that near-misses
      stopping before the payline were rated as more motivating than near-misses that
      stopped after the payline, and this differentiation was attenuated in the IGD
      group, suggesting possible counterfactual thinking deficits in this group. These
      data provide preliminary evidence for increased incentive motivation and
      cognitive distortions in IGD, at least in the context of a chance-based gambling
      environment.

PMID- 29346435
TI  - Influenza A virus hemagglutinin glycosylation compensates for antibody escape
      fitness costs.
AB  - Rapid antigenic evolution enables the persistence of seasonal influenza A and B
      viruses in human populations despite widespread herd immunity. Understanding
      viral mechanisms that enable antigenic evolution is critical for designing
      durable vaccines and therapeutics. Here, we utilize the primerID method of error
      correcting viral population sequencing to reveal an unexpected role for
      hemagglutinin (HA) glycosylation in compensating for fitness defects resulting
      from escape from anti-HA neutralizing antibodies. Antibody-free propagation
      following antigenic escape rapidly selected viruses with mutations that modulated
      receptor binding avidity through the addition of N-linked glycans to the HA
      globular domain. These findings expand our understanding of the viral mechanisms
      that maintain fitness during antigenic evolution to include glycan addition, and
      highlight the immense power of high-definition virus population sequencing to
      reveal novel viral adaptive mechanisms.

PMID- 29346436
TI  - Bone marrow concentrate promotes bone regeneration with a suboptimal-dose of
      rhBMP-2.
AB  - Bone marrow concentrate (BMC), which is enriched in mononuclear cells (MNCs) and
      platelets, has recently attracted the attention of clinicians as a new optional
      means for bone engineering. We previously reported that the osteoinductive effect
      of bone morphogenetic protein-2 (BMP-2) could be enhanced synergistically by co
      transplantation of peripheral blood (PB)-derived platelet-rich plasma (PRP). This
      study aims to investigate whether BMC can effectively promote bone formation
      induced by low-dose BMP-2, thereby reducing the undesirable side-effects of BMP
      2, compared to PRP. Human BMC was obtained from bone marrow aspirates using an
      automated blood separator. The BMC was then seeded onto beta-TCP granules pre
      adsorbed with a suboptimal-dose (minimum concentration to induce bone formation
      at 2 weeks in mice) of recombinant human (rh) BMP-2. These specimens were
      transplanted subcutaneously to the dorsal skin of immunodeficient-mice and the
      induction of ectopic bone formation was assessed 2 and 4 weeks post
      transplantation. Transplantations of five other groups [PB, PRP, platelet-poor
      plasma (PPP), bone marrow aspirate (BM), and BM-PPP] were employed as
      experimental controls. Then, to clarify the effects on vertical bone
      augmentation, specimens from the six groups were transplanted for on-lay
      placement on the craniums of mice. The results indicated that BMC, which
      contained an approximately 2.5-fold increase in the number of MNCs compared to
      PRP, could accelerate ectopic bone formation until 2 weeks post-transplantation.
      On the cranium, the BMC group promoted bone augmentation with a suboptimal-dose
      of rhBMP-2 compared to other groups. Particularly in the BMC specimens harvested
      at 4 weeks, we observed newly formed bone surrounding the TCP granules at sites
      far from the calvarial bone. In conclusion, the addition of BMC could reduce the
      amount of rhBMP-2 by one-half via its synergistic effect on early-phase
      osteoinduction. We propose here that BMC transplantation facilitates the clinical
      use of rhBMP-2 as an alternative strategy for bone engineering.

PMID- 29346437
TI  - Tissue-specific transcriptome analyses provide new insights into GPCR signalling
      in adult Schistosoma mansoni.
AB  - Schistosomes are blood-dwelling trematodes with global impact on human and animal
      health. Because medical treatment is currently based on a single drug,
      praziquantel, there is urgent need for the development of alternative control
      strategies. The Schistosoma mansoni genome project provides a platform to study
      and connect the genetic repertoire of schistosomes to specific biological
      functions essential for successful parasitism. G protein-coupled receptors
      (GPCRs) form the largest superfamily of transmembrane receptors throughout the
      Eumetazoan phyla, including platyhelminths. Due to their involvement in diverse
      biological processes, their pharmacological importance, and proven druggability,
      GPCRs are promising targets for new anthelmintics. However, to identify candidate
      receptors, a more detailed understanding of the roles of GPCR signalling in
      schistosome biology is essential. An updated phylogenetic analysis of the S.
      mansoni GPCR genome (GPCRome) is presented, facilitated by updated genome data
      that allowed a more precise annotation of GPCRs. Additionally, we review the
      current knowledge on GPCR signalling in this parasite and provide new insights
      into the potential roles of GPCRs in schistosome reproduction based on the
      findings of a recent tissue-specific transcriptomic study in paired and unpaired
      S. mansoni. According to the current analysis, GPCRs contribute to gonad-specific
      functions but also to nongonad, pairing-dependent processes. The latter may
      regulate gonad-unrelated functions during the multifaceted male-female
      interaction. Finally, we compare the schistosome GPCRome to that of another
      parasitic trematode, Fasciola, and discuss the importance of GPCRs to basic and
      applied research. Phylogenetic analyses display GPCR diversity in free-living and
      parasitic platyhelminths and suggest diverse functions in schistosomes. Although
      their roles need to be substantiated by functional studies in the future, the
      data support the selection of GPCR candidates for basic and applied studies,
      invigorating the exploitation of this important receptor class for drug discovery
      against schistosomes but also other trematodes.

PMID- 29346438
TI  - Colonization of the cervicovaginal space with Gardnerella vaginalis leads to
      local inflammation and cervical remodeling in pregnant mice.
AB  - The role of the cervicovaginal (CV) microbiome in regulating cervical function
      during pregnancy is poorly understood. Gardnerella vaginalis (G. vaginalis) is
      the most common bacteria associated with the diagnosis of bacterial vaginosis
      (BV). While BV has been associated with preterm birth (PTB), clinical trials
      targeting BV do not decrease PTB rates. It remains unknown if G. vaginalis is
      capable of triggering molecular, biomechanical and cellular events that could
      lead to PTB. The objective of this study was to determine if cervicovaginal
      colonization with G. vaginalis, in pregnant mice, induced cervical remodeling and
      modified cervical function. CD-1 timed-pregnant mice received a 5X108 CFU/mL
      intravaginal inoculation of G. vaginalis or control on embryonic day 12 (E12) and
      E13. On E15, the mice were sacrificed and cervicovaginal fluid (CVF), amniotic
      fluid (AF), cervix, uterus, placentas and fetal membranes (FM) were collected.
      Genomic DNA was isolated from the CVF, placenta, uterus and FM and QPCR was
      performed to confirm colonization. IL-6 was measured in the CVF and AF and
      soluble e-cadherin (seCAD) was assessed in the CVF by ELISA. RNA was extracted
      from the cervices to evaluate IL-10, IL-8, IL-1beta, TNF-alpha, Tff-1, SPINK-5,
      HAS-1 and LOX expression via QPCR. Mucicarmine and trichrome staining was used to
      assess cervical mucin and collagen. Biomechanical properties of the cervix were
      studied using quasi-static tensile load-to-failure biomechanical tests. G.
      vaginalis successfully colonized the CV space. This colonization induced immune
      responses (increased IL-6 levels in CVF and AF, increased mRNA expression of
      cervical cytokines), altered the epithelial barrier (increased seCAD in the CVF),
      induced cervical remodeling (increased mucin production, altered collagen) and
      altered cervical biomechanical properties (a decrease in biomechanical modulus
      and an increase in maximum strain). The ability of G. vaginalis to induce these
      molecular, immune, cellular and biomechanical changes suggests that this
      bacterium may play a pathogenic role in premature cervical remodeling leading to
      PTB.

PMID- 29346439
TI  - Interspecies diversity of chloride channel regulators, calcium-activated 3 genes.
AB  - Members of the chloride channel regulators, calcium-activated (CLCA) family, have
      been implicated in diverse biomedical conditions, including chronic inflammatory
      airway diseases such as asthma, chronic obstructive pulmonary disease, and cystic
      fibrosis, the activation of macrophages, and the growth and metastatic spread of
      tumor cells. Several observations, however, could not be repeated across species
      boundaries and increasing evidence suggests that select CLCA genes are
      particularly prone to dynamic species-specific evolvements. Here, we
      systematically characterized structural and expressional differences of the CLCA3
      gene across mammalian species, revealing a spectrum of gene duplications, e.g.,
      in mice and cows, and of gene silencing via diverse chromosomal modifications in
      pigs and many primates, including humans. In contrast, expression of a canonical
      CLCA3 protein from a single functional gene seems to be evolutionarily retained
      in carnivores, rabbits, guinea pigs, and horses. As an accepted asthma model, we
      chose the cat to establish the tissue and cellular expression pattern of the
      CLCA3 protein which was primarily found in mucin-producing cells of the
      respiratory tract and in stratified epithelia of the esophagus. Our results
      suggest that, among developmental differences in other CLCA genes, the CLCA3 gene
      possesses a particularly high dynamic evolutionary diversity with pivotal
      consequences for humans and other primates that seem to lack a CLCA3 protein. Our
      data also help to explain previous contradictory results on CLCA3 obtained from
      different species and warrant caution in extrapolating data from animal models in
      conditions where CLCA3 may be involved.

PMID- 29346440
TI  - Geographical distribution of soil transmitted helminths and the effects of
      community type in South Asia and South East Asia - A systematic review.
AB  - BACKGROUND: Soil-transmitted helminth (STH) infections are among the most
      prevalent neglected tropical diseases (NTD) worldwide. Since the publication of
      the WHO road map to combat NTD in 2012, there has been a renewed commitment to
      control STH. In this study, we analysed the geographical distribution and effect
      of community type on prevalence of hookworm, Trichuris and Ascaris in south Asia
      and south east Asia. METHODOLOGY: We conducted a systematic review of open-access
      literature published in PubMed Central and the Global Atlas of Helminth
      Infection. A total of 4182 articles were available and after applying selection
      criteria, 174 studies from the region were retained for analysis. PRINCIPAL
      FINDINGS: Ascaris was the commonest STH identified with an overall prevalence of
      18% (95% CI, 14-23%) followed by Trichuris (14%, 9-19%) and hookworm (12%, 9
      15%). Hookworm prevalence was highest in Laos, Vietnam and Cambodia. We found a
      geographical overlap in countries with high prevalence rates for Trichuris and
      Ascaris (Malaysia, Philippines, Myanmar, Vietnam and Bangladesh). When the effect
      of community type was examined, prevalence rates of hookworm was comparable in
      rural (19%, 14-24%) and tribal communities (14%, 10-19%). Tribal communities,
      however, showed higher prevalence of Trichuris (38%, 18-63%) and Ascaris (32%, 23
      43%) than rural communities (13%, 9-20% and 14%, 9-20% respectively).
      Considerable between and within country heterogeneity in the distribution of STH
      (I2 >90%) was also noted. When available data from school aged children (SAC)
      were analysed, prevalence of Ascaris (25% 16-31%) and Trichuris (22%, 14-34%)
      were higher than among the general population while that of hookworm (10%, 7-16%)
      was comparable. CONCLUSIONS/SIGNIFICANCE: Our analysis showed significant
      variation in prevalence rates between and within countries in the region.
      Highlighting the importance of community type in prevalence and species mix, we
      showed that tribal and rural communities had higher hookworm infections than
      urban communities and for ascariasis and trichuriasis, tribal populations had
      higher levels of infection than rural populations. We also found a higher
      prevalence of ascariasis and trichuriasis in SAC compared to the general
      population but comparable levels of hookworm infections. These key findings need
      to be taken into account in planning future MDA and other interventions.

PMID- 29346441
TI  - A portable system for processing donated whole blood into high quality components
      without centrifugation.
AB  - BACKGROUND: The use of centrifugation-based approaches for processing donated
      blood into components is routine in the industrialized world, as disparate
      storage conditions require the rapid separation of 'whole blood' into distinct
      red blood cell (RBC), platelet, and plasma products. However, the logistical
      complications and potential cellular damage associated with
      centrifugation/apheresis manufacturing of blood products are well documented. The
      objective of this study was to evaluate a proof-of-concept system for whole blood
      processing, which does not employ electromechanical parts, is easily portable,
      and can be operated immediately after donation with minimal human labor. METHODS
      AND FINDINGS: In a split-unit study (n = 6), full (~500mL) units of freshly
      donated whole blood were divided, with one half processed by conventional
      centrifugation techniques and the other with the new blood separation system.
      Each of these processes took 2-3 hours to complete and were performed in
      parallel. Blood products generated by the two approaches were compared using an
      extensive panel of cellular and plasma quality metrics. Comparison of nearly all
      RBC parameters showed no significant differences between the two approaches,
      although the portable system generated RBC units with a slight but statistically
      significant improvement in 2,3-diphosphoglyceric acid concentration (p < 0.05).
      More notably, several markers of platelet damage were significantly and
      meaningfully higher in products generated with conventional centrifugation: the
      increase in platelet activation (assessed via P-selectin expression in platelets
      before and after blood processing) was nearly 4-fold higher for platelet units
      produced via centrifugation, and the release of pro-inflammatory mediators
      (soluble CD40-ligand, thromboxane B2) was significantly higher for centrifuged
      platelets as well (p < 0.01). CONCLUSION: This study demonstrated that a simple,
      passive system for separating donated blood into components may be a viable
      alternative to centrifugation-particularly for applications in remote or resource
      limited settings, or for patients requiring highly functional platelet product.

PMID- 29346442
TI  - Comparative metabolic ecology of tropical herbivorous echinoids on a coral reef.
AB  - BACKGROUND: The metabolic rate of consumers is a key driver of ecosystem
      dynamics. On coral reefs, herbivorous echinoids consume fleshy algae,
      facilitating the growth of reef-building calcified organisms; however, little is
      known about differences among species in their metabolic and functional ecology.
      Here, we used log-linear (log-log) regression models to examine the allometric
      scaling of mass and routine metabolic rate for five common herbivorous echinoids
      on a Hawaiian coral reef: Echinothrix calamaris, E. diadema, Echinometra
      matthaei, Heterocentrotus mammillatus, and Tripneustes gratilla. Scaling
      relationships were then contrasted with empirical observations of echinoid
      ecology and general metabolic theory to broaden our understanding of diversity in
      the metabolic and functional ecology of tropical herbivorous echinoids. RESULTS:
      Test diameter and species explained 98% of the variation in mass, and mass and
      species explained 92.4% and 87.5% of the variation in individual (I) and mass
      specific (B) metabolic rates, respectively. Scaling exponents did not differ for
      mass or metabolism; however, normalizing constants differed significantly among
      species. Mass varied as the cube of test diameter (b = 2.9), with HM exhibiting a
      significantly higher normalizing constant than other species, likely due to its
      heavily-calcified spines and skeleton. Individual metabolic rate varied
      approximately as the 2/5 power of mass (gamma = 0.44); significantly smaller than
      the 3/4 universal scaling coefficient, but inclusive of 2/3 scaling. E. calamaris
      and H. mammillatus exhibited the lowest normalizing constants, corresponding with
      their slow-moving, cryptic, rock-boring life-history. In contrast, E. calamaris,
      E. diadema, and T. gratilla, exhibited higher metabolic rates, likely reflecting
      their higher levels of activity and ability to freely browse for preferred algae
      due to chemical anti-predator defenses. Thus, differences in metabolic scaling
      appeared to correspond with differences in phylogeny, behavior, and ecological
      function. Such comparative metabolic assessments are central to informing theory,
      ecological models, and the effective management of ecosystems.

PMID- 29346443
TI  - Exposure to previous cART is associated with significant liver fibrosis and
      cirrhosis in human immunodeficiency virus-infected patients.
AB  - INTRODUCTION: Combined antiretroviral therapy (cART) has improved survival in HIV
      patients. While the first antiretrovirals, which became available in particular D
      drugs (especially didanosine and stavudine) and unboosted protease inhibitors,
      may impair liver function, the modern cART seems to decrease liver fibrosis. This
      study assessed the influence of exposure to previous antiretrovirals on liver
      fibrosis in HIV-infected patients. METHODS: This observational cross-sectional
      single-center study recruited 333 HIV patients and assessed liver fibrosis using
      transient elastography (TE). RESULTS: 83% were male with a median age of 45,
      while 131 were co-infected with viral hepatitis. Overall, 18% had significant
      fibrosis and 7.5% had cirrhosis. 11% of HIV mono-infected patients had
      significant fibrosis and 2% had cirrhosis. HCV infection (OR:5.3), history of
      exposure to didanosine (OR:2.7) and HIV load below 40copies/mL (OR:0.5) were
      independently associated with significant fibrosis, while HCV (OR:5.8), exposure
      to didanosine (OR:2.9) and azidothymidine (OR:2.8) were independently associated
      with cirrhosis. Interestingly, in HIV mono-infected patients, a HIV-load below
      40copies/mL (OR:0.4) was independently associated with significant fibrosis, and
      didanosine (OR:20.8) with cirrhosis. CONCLUSION: In conclusion, history of
      exposure to didanosine and azidothymidine continues to have an impact on the
      presence of liver cirrhosis in HIV patients. However, HCV co-infection and
      ongoing HIV-replication have the strongest effect on development of significant
      fibrosis in these patients.

PMID- 29346444
TI  - Social and structural barriers for adherence to methadone maintenance treatment
      among Vietnamese opioid dependence patients.
AB  - INTRODUCTION: Methadone maintenance treatment (MMT) services may reduce the risk
      of HIV transmission if patients completely adhere to the treatment. Identifying
      adherence patterns and potential related factors is vital for the sustainability
      of MMT program in Vietnam. This study examined social and structural factors
      associated with adherence to MMT among patients in different service delivery
      models. MATERIALS AND METHODS: A total of 510 patients at three MMT clinics in
      Hanoi were interviewed. Measures of self-reported adherence included the number
      of missed doses in the past 7 days and the level of adherence in the past 30 days
      using a visual analog scale (VAS) scoring from 0 (non-adherence) to 100 (perfect
      adherence). Multivariate regressions were employed to identify factors associated
      with non-adherence to MMT. RESULTS: A total of 17.7% of participants reported
      incomplete MMT adherence in the last 30 days and 8.3% reported missing a dose in
      the last seven days, respectively. Living with HIV/AIDS, poor self-care and usual
      activities, and disclosure of health issues to spouses or intimate partners were
      associated with non-adherence. Those patients with pain or depression were more
      likely to report better adherence. Disclosing health status to spouse/partner
      increased the risk of incomplete adherence, while disclosing to friends reduced
      the number of missed dose in the last seven days. Patients attending clinics with
      comprehensive services had a lower VAS score of adherence compared to those
      enrolling in clinics with only MMT and general health care. CONCLUSIONS:
      Sustaining the compliance of patients to MMT is principal in the rapid expansion
      of this service in Vietnam. It is necessary to address the complexity of health
      care demands of drug users, their difficulties to be rehabilitated into workforce
      and society, and the stigmatization to maximize the outcomes of MMT program.

PMID- 29346445
TI  - Transcriptome analysis of skin fibroblasts with dominant negative COL3A1
      mutations provides molecular insights into the etiopathology of vascular Ehlers
      Danlos syndrome.
AB  - Vascular Ehlers-Danlos syndrome (vEDS) is a dominantly inherited connective
      tissue disorder caused by mutations in the COL3A1 gene that encodes type III
      collagen (COLLIII), which is the major expressed collagen in blood vessels and
      hollow organs. The majority of disease-causing variants in COL3A1 are glycine
      substitutions and in-frame splice mutations in the triple helix domain that
      through a dominant negative effect are associated with the severe clinical
      spectrum potentially lethal of vEDS, characterized by fragility of soft
      connective tissues with arterial and organ ruptures. To shed lights into
      molecular mechanisms underlying vEDS, we performed gene expression profiling in
      cultured skin fibroblasts from three patients with different structural COL3A1
      mutations. Transcriptome analysis revealed significant changes in the expression
      levels of several genes involved in maintenance of cell redox and endoplasmic
      reticulum (ER) homeostasis, COLLs folding and extracellular matrix (ECM)
      organization, formation of the proteasome complex, and cell cycle regulation.
      Protein analyses showed that aberrant COLLIII expression is associated with the
      disassembly of many structural ECM constituents, such as fibrillins, EMILINs, and
      elastin, as well as with the reduction of the proteoglycans perlecan, decorin,
      and versican, all playing an important role in the vascular system. Furthermore,
      the altered distribution of the ER marker protein disulfide isomerase PDI and the
      strong reduction of the COLLs-modifying enzyme FKBP22 are consistent with the
      disturbance of ER-related homeostasis and COLLs biosynthesis and post
      translational modifications, indicated by microarray analysis. Our findings add
      new insights into the pathophysiology of this severe vascular disorder, since
      they provide a picture of the gene expression changes in vEDS skin fibroblasts
      and highlight that dominant negative mutations in COL3A1 also affect post
      translational modifications and deposition into the ECM of several structural
      proteins crucial to the integrity of soft connective tissues.

PMID- 29346446
TI  - Osteopontin (OPN) as a CSF and blood biomarker for multiple sclerosis: A
      systematic review and meta-analysis.
AB  - Identifying a reliable biomarker may accelerate diagnosis of multiple sclerosis
      (MS) and lead to early management of the disease. Accumulating evidence suggest
      that cerebrospinal fluid (CSF) and peripheral blood concentration of osteopontin
      (OPN) may have diagnostic and prognostic value in MS. We conducted a systematic
      review and meta-analysis of studies that measured peripheral blood and CSF levels
      of OPN in MS patients and controls to evaluate the diagnostic potential of this
      biomarker better. We searched PubMed, Web of Science and Scopus databases to find
      articles that measured OPN concentration in peripheral blood and CSF samples from
      MS patients up to October 19, 2016. Q statistic tests and the I2 index were
      applied for heterogeneity assessment. If the I2 index was less than 40%, the
      fixed-effects model was used for meta-analysis. Random-effects meta-analysis was
      chosen if the I2 value was greater than 40%. After removal of duplicates, 918
      articles were identified, and 27 of them fulfilled the inclusion criteria. We
      included 22 eligible studies in the final meta-analysis. MS patients, in general,
      had considerably higher levels of OPN in their CSF and blood when compared to all
      types of controls (p<0.05). When the comparisons were made between different
      subtypes of MS patients and controls, the results pointed to significantly higher
      levels of OPN in CSF of MS subgroups (p<0.05). All subtypes of MS patients,
      except CIS patients, had increased blood levels of OPN compared to controls
      (p<0.05). In the second set of meta-analyses, we compared the peripheral blood
      and CSF concentrations of OPN between MS patient subtypes. CIS patients had
      significantly lower levels of OPN both in their peripheral blood and CSF compared
      to patients with progressive subtypes of MS (p<0.05). CSF concentration of OPN
      was significantly higher among RRMS patients compared to the CIS patients and
      SPMS patients (P<0.05). Finally, patients with active MS had significantly higher
      OPN levels in their CSF compared to patients with stable disease (P = 0.007). The
      result of this study confirms that increased levels of OPN exist in CSF and
      peripheral blood of MS patients and strengthens the evidence regarding the
      clinical utility of OPN as a promising and validated biomarker for MS.

PMID- 29346447
TI  - Pik3ca is required for mouse uterine gland development and pregnancy.
AB  - The PI3K/AKT signaling pathway plays a critical role in the maintenance of
      equilibrium between cell survival and apoptosis. The Pik3ca gene is mutated in a
      range of human cancers. It has been found to be oncogenic, and mutations lead to
      constitutive activation of the PI3K/AKT pathway. The expression patterns of
      PIK3CA proteins in the uterus of mice during early pregnancy indicate that it may
      play a role in the regulation of glandular epithelial cells, which is required to
      support uterine receptivity. To further investigate the role of Pik3ca in uterine
      function, Pik3ca was conditionally ablated only in the PGR-positive cells
      (Pgrcre/+Pik3caf/f; Pik3cad/d). A defect of uterine gland development and
      decidualization led to subfertility observed in Pik3cad/d mice. Pik3cad/d mice
      showed significantly decreased uterine weight compared to Pik3caf/f mice.
      Interestingly, a significant decrease of gland numbers were detected in Pik3cad/d
      mice compared to control mice. In addition, we found a decrease of Foxa2
      expression, which is a known uterine gland marker in Pik3cad/d mice. Furthermore,
      the excessive proliferation of endometrial epithelial cells was observed in
      Pik3cad/d mice. Our studies suggest that Pik3ca has a critical role in uterine
      gland development and female fertility.

PMID- 29346449
TI  - Within host selection for faster replicating bacterial symbionts.
AB  - Wolbachia is a widespread, intracellular symbiont of arthropods, able to induce
      reproductive distortions and antiviral protection in insects. Wolbachia can also
      be pathogenic, as is the case with wMelPop, a virulent variant of the
      endosymbiont of Drosophila melanogaster. An extensive genomic amplification of
      the 20kb region encompassing eight Wolbachia genes, called Octomom, is
      responsible for wMelPop virulence. The Octomom copy number in wMelPop can be
      highly variable between individual D. melanogaster flies, even when comparing
      siblings arising from a single female. Moreover, Octomom copy number can change
      rapidly between generations. These data suggest an intra-host variability in
      Octomom copy number between Wolbachia cells. Since wMelPop Wolbachia with
      different Octomom copy numbers grow at different rates, we hypothesized that
      selection could act on this intra-host variability. Here we tested if total
      Octomom copy number changes during the lifespan of individual Drosophila hosts,
      revealing selection for different Wolbachia populations. We performed a time
      course analysis of Octomom amplification in flies whose mothers were controlled
      for Octomom copy number. We show that despite the Octomom copy number being
      relatively stable it increases slightly throughout D. melanogaster adult life.
      This indicates that there is selection acting on the intra-host variation in the
      Octomom copy number over the lifespan of individual hosts. This within host
      selection for faster replicating bacterial symbionts may be in conflict with
      between host selection against highly pathogenic Wolbachia.

PMID- 29346448
TI  - A cross-sectional study to estimate prevalence of periodontal disease in a
      population of dogs (Canis familiaris) in commercial breeding facilities in
      Indiana and Illinois.
AB  - The objectives of this cross-sectional study were: 1) to estimate the prevalence
      and characterize the severity of periodontal disease in a population of dogs
      housed in commercial breeding facilities; 2) to characterize PD preventive care
      utilized by facility owners; and 3) to assess inter-rater reliability of a visual
      scoring assessment tool. Adult dogs (N = 445) representing 42 breeds at 24 CB
      facilities in Indiana and Illinois were assessed. Periodontal disease was scored
      visually using the American Veterinary Dental Collage 0-IV scale. Inter-rater
      reliability was assessed on 198 dogs and facility owners were asked to provide
      information about the preventive care utilized. The overall prevalence of
      periodontal disease (Grades I-IV) was 86.3% (95% CI: 82.9, 89.3). An ordered
      logistic regression analysis found age (OR = 1.4; 95% CI 1.24, 1.54; P<0.0001),
      facility (OR = 1.13; 95% CI 1.09, 1.18; P<0.0001), sex (OR = 1.7; 95% CI 1.12,
      2.65; P = 0.013), and non-professional dental scaling (OR = 2.82; 95% CI 1.34,
      5.91; P = 0.006) to be statistically significant. Inter-rater reliability
      analysis found agreement to be 86.2%, with a weighted kappa of 0.4731 (95% CI
      0.3847, 0.5615) indicating moderate agreement. Risk of periodontal disease
      increased with increasing age. Additionally, a trend toward decreasing risk with
      increasing weight was also found, although it was not statistically significant.
      The trends identified agree with studies that have evaluated periodontal disease
      in the companion dog population and do not support the assumption that the dental
      health of dogs in commercial breeding facilities is worse than that of the
      population as a whole. Although there were few cases of severe periodontal
      disease and all facilities employed some type of preventive care in this sample,
      the large number of dogs with some degree of disease (Grades I-IV) suggests that
      further investigation of preventive care is warranted.

PMID- 29346450
TI  - Cloning and spatiotemporal expression of Xenopus laevis Apolipoprotein CI.
AB  - Apolipoprotein CI (ApoCI) belongs to the Apolipoprotein superfamily, members of
      which are involved in lipid transport, uptake and homeostasis. Excessive ApoCI
      has been implicated in atherosclerosis and Alzheimer's disease in humans. In this
      study we report the isolation of Xenopus laevis apoCI and describe the expression
      pattern of this gene during early development, using reverse transcription
      polymerase chain reaction and whole mount in situ hybridization. Xenopus apoCI is
      enriched in the dorsal ectoderm during gastrulation, and is subsequently
      expressed in sensory placodes, neural tube and cranial neural crest. These data
      suggest as yet uncharacterized roles for ApoCI during early vertebrate
      embryogenesis.

PMID- 29346451
TI  - An approach for predicting the compressive strength of cement-based materials
      exposed to sulfate attack.
AB  - In this paper, a support vector machine (SVM) model which can be used to predict
      the compressive strength of mortars exposed to sulfate attack was established. An
      accelerated corrosion test was applied to collect compressive strength data. For
      predicting the compressive strength of mortars, a total of 638 data samples
      obtained from experiment was chosen as a dataset to establish a SVM model. The
      values of the coefficient of determination, the mean absolute error, the mean
      absolute percentage error and the root mean square error were used for evaluating
      the predictive accuracy. The main factors affecting the predicted compressive
      strength were obtained by sensitivity analysis. A SVM model was calibrated,
      validated, and finally established. Moreover, the performance of the SVM model
      was compared to an artificial neural network (ANN) model. Results show that the
      prediction values from the SVM model were close to the experimental values; the
      main factors sensitive to concrete compressive strength were exposure time, water
      cement ratio and sulfate ions; the performance of the SVM model was better than
      the ANN model. The SVM model developed in this study can be potentially used for
      predicting the compressive strength of cement-based materials servicing in harsh
      environments.

PMID- 29346452
TI  - Body shape indices are predictors for estimating fat-free mass in male athletes.
AB  - It is unknown whether body size and body shape parameters can be predictors for
      estimating whole body fat-free mass (FFM) in male athletes. This study aimed to
      investigate whether body size and shape variables can be predictors for FFM in
      male athletes. Using a whole-body dual-energy X-ray absorptiometry scanner, whole
      body fat mass (FM) and FFM were determined in 132 male athletes and 14 sedentary
      males. The sample was divided into two groups: validation (N = 98) and cross
      validation (N = 48) groups. Body height (BH), body mass (BM), and waist
      circumference at immediately above the iliac crest (W) were measured. BM-to-W and
      W-to-BH ratios were calculated as indices of body shapes. Stepwise multiple
      regression analysis revealed that BM/W and W/BH were selected as explainable
      variables for predicting FFM. The equation developed in the validation group was
      FFM (kg) = 0.883 * BM/W (kg/m) + 43.674 * W/BH (cm/cm)- 41.480 [R2 = 0.900, SEE
      (%SEE) = 2.3 kg (3.8%)], which was validated in the cross-validation group. Thus,
      the current results demonstrate that an equation using BM/W and W/BH as
      independent variables is applicable for predicting FFM in male athletes.

PMID- 29346453
TI  - Yearly fluctuations of flower landscape in a Mediterranean scrubland:
      Consequences for floral resource availability.
AB  - Species flower production and flowering phenology vary from year to year due to
      extrinsic factors. Inter-annual variability in flowering patterns may have
      important consequences for attractiveness to pollinators, and ultimately, plant
      reproductive output. To understand the consequences of flowering pattern
      variability, a community approach is necessary because pollinator flower choice
      is highly dependent on flower context. Our objectives were: 1) To quantify yearly
      variability in flower density and phenology; 2) To evaluate whether changes in
      flowering patterns result in significant changes in pollen/nectar composition. We
      monitored weekly flowering patterns in a Mediterranean scrubland community (23
      species) over 8 years. Floral resource availability was estimated based on field
      measures of pollen and nectar production per flower. We analysed inter-annual
      variation in flowering phenology (duration and date of peak bloom) and flower
      production, and inter-annual and monthly variability in flower, pollen and nectar
      species composition. We also investigated potential phylogenetic effects on inter
      annual variability of flowering patterns. We found dramatic variation in yearly
      flower production both at the species and community levels. There was also
      substantial variation in flowering phenology. Importantly, yearly fluctuations
      were far from synchronous across species, and resulted in significant changes in
      floral resources availability and composition at the community level. Changes
      were especially pronounced late in the season, at a time when flowers are scarce
      and pollinator visitation rates are particularly high. We discuss the
      consequences of our findings for pollinator visitation and plant reproductive
      success in the current scenario of climate change.

PMID- 29346454
TI  - More Unified Analysis of Medical Imaging System SNR Characteristics.
AB  - The ideal observer signal-to-noise ratio has been derived from statistical
      decision theory for all of the major medical imaging modalities. This yields an
      absolute scale for image performance assessment and instrumentation design and
      optimization. Applications include: the functional dependence of detectable
      detail size on exposure or imaging time; a framework for comparing data
      acquisition techniques, e.g., Fourier methods vs reconstruction from projections
      in NMR imaging; calculations of realizable limits, e.g., the limiting gain of
      time-of-flight PET scanning. Measurements on human observers show that they can
      come close to ideal performance, except when the noise has negative correlations
      as in images reconstructed from projections. In this latter case they suffer a
      small but significant penalty.

PMID- 29346455
TI  - Response: Concerns with conclusions in the article by Sherwood et al 'Key
      differences between 13 KRAS mutation detection technologies and their relevance
      for clinical practice'.

PMID- 29346467
TI  - Modification of the Associations Between Duration of Oral Contraceptive Use and
      Ovarian, Endometrial, Breast, and Colorectal Cancers.
AB  - Importance: Although oral contraceptive (OC) use is common, the influence of OC
      use on carcinogenesis is not fully understood. A recent Agency for Healthcare
      Research and Quality report identified a need to understand the consistency of OC
      use and cancer associations across subpopulations, including smokers and obese
      women. Objective: To determine whether associations between duration of OC use
      and risk of specific cancers were modified by lifestyle characteristics. Design,
      Setting, and Participants: The prospective NIH-AARP Diet and Health Study
      (enrolled 1995-1996, followed until 2011), with population-based recruitment of
      AARP members in 6 states and 2 metropolitan areas. All analyses included at least
      100 000 women who reported OC use at enrollment. We identified 1241 ovarian, 2337
      endometrial, 11 114 breast, and 3507 colorectal cancer cases during follow-up.
      Data analysis was performed between September 2016 and April 2017. Exposures:
      Duration of OC use (never or <1 year [reference], 1-4, 5-9, or >=10 years). Main
      Outcomes and Measures: Development of ovarian, endometrial, breast, and
      colorectal cancers. We examined effect modification by modifiable lifestyle
      characteristics: cigarette smoking, alcohol consumption, body mass index (BMI),
      and physical activity. We used Cox models adjusted for age, race, age at
      menarche, and the modifiers of interest. Results: The analytic population was
      aged 50 to 71 years (median, 62 years) at enrollment and largely white (91%) and
      postmenopausal (96%). For ovarian cancer, OC use-associated risk reductions
      strengthened with duration of use (long-term OC use [>=10 years] HR, 0.60; 95%
      CI, 0.47-0.76; P < .001 for trend) and were similar across modifiable lifestyle
      factors. Risk reductions for endometrial cancer strengthened with duration of use
      (long-term OC use HR, 0.66; 95% CI, 0.56-0.78; P < .001 for trend); the most
      pronounced reductions were among long-term OC users who were smokers (HR, 0.47;
      95% CI, 0.25-0.88), had obese BMIs (0.36; 95% CI, 0.25-0.52), and who exercised
      rarely (HR, 0.40; 95% CI, 0.29-0.56). Associations between OC use and breast and
      colorectal cancers were predominantly null. Conclusions and Relevance: Long-term
      OC use is consistently associated with reduced ovarian cancer risk across
      lifestyle factors. We observed the greatest risk reductions for endometrial
      cancer among women at risk for chronic diseases (ie, smokers, obese BMI). Oral
      contraceptive use may be beneficial for chemoprevention for a range of women with
      differing baseline cancer risks.

PMID- 29346468
TI  - Congenital Restrictive Strabismus.

PMID- 29346469
TI  - Identifying who lives in a care home-a challenge to be conquered.

PMID- 29346470
TI  - Proposal for a New Diagnosis for Cochlear Migraine.

PMID- 29346471
TI  - Use of Single-Nucleotide Polymorphisms and Mammographic Density Plus Classic Risk
      Factors for Breast Cancer Risk Prediction.
AB  - Importance: Single-nucleotide polymorphisms (SNPs) have demonstrated an
      association with breast cancer susceptibility, but there is limited evidence on
      how to incorporate them into current breast cancer risk prediction models.
      Objective: To determine whether a panel of 18 SNPs (SNP18) may be used to predict
      breast cancer in combination with classic risk factors and mammographic density.
      Design, Setting, and Participants: This cohort study enrolled a subcohort of 9363
      women, aged 46 to 73 years, without a previous breast cancer diagnosis from the
      larger prospective cohort of the PROCAS study (Predicting Risk of Cancer at
      Screening) specifically to evaluate breast cancer risk-assessment methods.
      Enrollment took place from October 2009 through June 2015 from multiple
      population-based screening centers in Greater Manchester, England. Follow-up
      continued through January 5, 2017. Exposures: Genotyping of 18 SNPs, visual
      assessment percentage mammographic density, and classic risk assessed by the
      Tyrer-Cuzick risk model from a self-completed questionnaire at cohort entry. Main
      Outcomes and Measures: The predictive ability of SNP18 for breast cancer
      diagnosis (invasive and ductal carcinoma in situ) was assessed using logistic
      regression odds ratios per interquartile range of the predicted risk. Results: A
      total of 9363 women were enrolled in this study (mean [range] age, 59 [46-73]
      years). Of these, 466 were found to have breast cancer (271 prevalent; 195
      incident). SNP18 was similarly predictive when unadjusted or adjusted for
      mammographic density and classic factors (odds ratios per interquartile range,
      respectively, 1.56; 95% CI, 1.38-1.77 and 1.53; 95% CI, 1.35-1.74), with observed
      risks being very close to expected (adjusted observed-to-expected odds ratio,
      0.98; 95% CI, 0.69-1.28). A combined risk assessment indicated 18% of the
      subcohort to be at 5% or greater 10-year risk, compared with 30% of all cancers,
      35% of interval-detected cancers, and 42% of stage 2+ cancers. In contrast, 33%
      of the subcohort were at less than 2% risk but accounted for only 18%, 17%, and
      15% of the total, interval, and stage 2+ breast cancers, respectively.
      Conclusions and Relevance: SNP18 added substantial information to risk assessment
      based on the Tyrer-Cuzick model and mammographic density. A combined risk is
      likely to aid risk-stratified screening and prevention strategies.

PMID- 29346472
TI  - A Revised Estimate of Costs Associated With Routine Preoperative Testing in
      Medicare Cataract Patients With a Procedure-Specific Indicator.
AB  - Importance: Routine preoperative medical testing is not recommended for patients
      undergoing low-risk surgery, but testing is common before surgery. A 30-day
      preoperative testing window is conventionally used for study purposes; however,
      the extent of routine testing that occurs prior to that point is unknown.
      Objective: To improve on existing cost estimates by identifying all routine
      preoperative testing that takes place after the decision is made to perform
      cataract surgery. Design, Setting, and Participants: This cross-sectional study
      assessed preoperative care in a 50% sample of Medicare beneficiaries older than
      66 years who underwent ambulatory cataract surgery in 2011. Data analysis was
      completed from March 2016 to October 2017. Main Outcomes and Measures: Using
      ocular biometry as a procedure-specific indicator to mark the start of the
      routine preoperative testing window, we measured testing rates in the interval
      between ocular biometry and cataract surgery and compared this with testing rates
      in the 6 months preceding biometry. We estimated the total cost of testing that
      occurred between biometry and cataract surgery. Results: A total of 440 857
      patients underwent cataract surgery. A total of 423 710 (96.1%) had an ocular
      biometry claim before index surgery, of whom 264 514 (60.0%) were female; the
      mean (SD) age of the cohort was 76.1 (6.2) years. A total of 111 998 (25.4%)
      underwent surgery more than 30 days after biometry. Among patients with a
      biometry claim, the mean number of tests/patient/month increased from 1.1 in the
      baseline period to 1.7 in the interval between biometry and cataract surgery.
      Although preoperative testing peaked in all patients in the 30 days preceding
      surgery (1.8 tests/patient/month), the subset of patients with no overlap between
      postbiometry and presurgery periods experienced increased testing rates to 1.8
      tests per patient per month in the 30 days after biometry, regardless of the
      elapsed time between biometry and surgery. The total estimated cost of routine
      preoperative testing in the full cohort was $22.7 million; we estimate that
      routine preoperative testing costs Medicare up to $45.4 million annually.
      Conclusions and Relevance: In this study of Medicare beneficiaries, routine
      preoperative medical testing occurs more often and is costlier than has been
      reported previously. Extra costs are attributable to testing that occurs prior to
      the 30-day window preceding surgery. As a cost-cutting measure, routine
      preoperative medical testing should be avoided in patients with cataracts
      throughout the interval between ocular biometry and cataract surgery.

PMID- 29346473
TI  - Treatment for Alcohol Dependence in Primary Care Compared to Outpatient
      Specialist Treatment-A Randomized Controlled Trial.
AB  - Aim: To investigate if treatment for alcohol dependence in primary care is as
      effective as specialist addiction care. Method: Randomized controlled non
      inferiority trial, between groups parallel design, not blinded. The non
      inferiority limit was set to 50 grams of alcohol per week. About 288 adults
      fulfilling ICD-10 criteria for alcohol dependence were randomized to treatment in
      primary care (men n = 82, women n = 62) or specialist care (men n = 77, women n =
      67). General practitioners at 12 primary care centers received 1-day training in
      a treatment manual for alcohol dependence. Primary outcome was change in weekly
      alcohol consumption at 6-months follow-up compared with baseline, as measured
      with timeline follow back. Secondary outcomes were heavy drinking days, severity
      of dependence, consequences of drinking, psychological health, quality of life,
      satisfaction with treatment and biomarkers. Results: Intention-to-treat analysis
      (n = 228) was statistically inconclusive, and could not confirm non-inferiority
      for the primary outcome, since the high end of the confidence interval exceeded
      50 grams (estimated mean weekly alcohol consumption was 30 grams higher in
      primary care compared with specialist care; 95% confidence interval -10.20;
      69.72). However, treatment in specialist care was not significantly superior to
      primary care (P = 0.146). Subanalysis suggests that specialist care was superior
      to primary care only for patients with high severity of dependence. Conclusions:
      Treatment for alcohol dependence in primary care is a promising approach,
      especially for individuals with low to moderate dependence. This may be a way to
      broaden the base of treatment for alcohol dependence, reducing the current
      treatment gap.

PMID- 29346474
TI  - Examining Nonparticipation in the Maternal Follow-up Within the Danish National
      Birth Cohort.
AB  - A follow-up questionnaire on maternal health was distributed within the Danish
      National Birth Cohort (established in 1996-2002) 14 years after the index birth.
      Responses were obtained from 41,466 (53.2%) of 78,010 eligible mothers. To ensure
      the appropriate use of these data, the possibility of selection bias due to
      nonparticipation had to be evaluated. We estimated 4 selected exposure-outcome
      associations (prepregnancy weight-depression; exercise-degenerative
      musculoskeletal conditions; smoking-heart disease; and alcohol consumption-breast
      cancer). We adjusted for several factors associated with participation and
      applied inverse probability weighting. To estimate the degree of selection bias,
      we calculated relative odds ratios for the relationship between the baseline
      cohort and the subset participating in the Maternal Follow-up. Participating
      women were generally healthier, of higher social status, and older than the
      baseline cohort. However, selection bias in the chosen scenarios was limited;
      ratios of the odds ratios ranged from -14% to 5% after adjustment for age,
      parity, social status, and, if the variable was not the exposure variable,
      prepregnancy body mass index, exercise, smoking, and alcohol consumption.
      Applying inverse probability weighting did not further reduce bias. In
      conclusion, while participants differed somewhat from the baseline cohort,
      selection bias was limited after factors associated with participation status
      were accounted for.

PMID- 29346476
TI  - Errors in Figures 1, 2, and 3.

PMID- 29346475
TI  - Current Status of Radiology Training in Otolaryngology Residency Programs.
AB  - Importance: Otolaryngologists use head and neck imaging on a daily basis.
      However, little is known about the training residents receive on the subject.
      Understanding the current training environment is important to identify areas of
      improvement for resident education. Objective: To assess the current state of
      radiology training in otolaryngology residency programs. Design, Setting, and
      Participants: This was a cross-sectional survey of 106 otolaryngology residency
      program directors involving multiple academic institutions. Main Outcomes and
      Measures: The main outcome of this study is the number of US otolaryngology
      residency programs that have a radiology curriculum. Measured outcomes were
      obtained from an anonymous online survey and reported as a percent of total
      respondents. Results: Program directors from 39 of 106 (37%) US otolaryngology
      residency training programs responded to the survey. Twenty-eight of 39 (71%)
      have a focused radiology curriculum; 18 of 28 (64%) conduct sessions on a monthly
      basis, 8 of 28 (29%) on a quarterly basis, and 2 of 28 (7%) on a weekly basis.
      The predominant format (20 of 27 programs [74%]) is a mix of case-based review of
      inpatient studies and standard lectures. The largest proportion of sessions were
      run by radiologists (13 of 28 [46%]), with a mix of radiology and
      otolaryngologists close behind (11 of 28 [39%]). Twenty-two of 39 residency
      programs (56%) have a dedicated radiology rotation within their educational
      curriculum, of which 17 of 22 (77%) occur in postgraduate year 1 (PGY-1) of
      training, 3 of 22 (14%) in PGY-3, and 2 of 22 (9%) in PGY-4. Rotation lengths
      range from 1 week to 3 months, with most running 1 to 4 weeks. Thirty-two of 38
      of US program directors (84%) believe that a formal radiology curriculum would
      benefit their residents. Thirty-five of 39 believe that this should be a case
      based review of images. Twenty-four of 38 believe this should be done on a
      monthly basis. Fifteen of 39 responding program directors (39%) believe the
      optimal time is during the PGY-3 of training, 36% (14 of 38) favor the PGY-2, and
      23% (9 of 38) in PGY-1. Conclusions and Relevance: Despite no standardized
      requirements from the Accreditation Council for Graduate Medical Education
      (ACGME), 71% of US otolaryngology residency program directors who responded to
      our survey have a radiology curriculum. Most run didactics sessions at the
      desired frequency, setting, and format preferred by responding program directors.
      More than half of programs provide a dedicated radiology rotation, mostly during
      PGY-1, while identifying PGY-2 and PGY-3 as the optimal time for such an
      experience. These results highlight the need for a more thorough review of
      radiology education requirements from the ACGME to improve the training of
      otolaryngology residents across the country.

PMID- 29346477
TI  - Enasidenib-Induced Differentiation Syndrome in IDH2-Mutant Acute Myeloid
      Leukemia.

PMID- 29346478
TI  - Differentiation Syndrome Associated With Enasidenib, a Selective Inhibitor of
      Mutant Isocitrate Dehydrogenase 2: Analysis of a Phase 1/2 Study.
AB  - Importance: Enasidenib mesylate, a mutant isocitrate dehydrogenase 2 (IDH2)
      protein inhibitor that promotes differentiation of leukemic myeloblasts, was
      recently approved by the US Food and Drug Administration for use in
      relapsed/refractory (R/R) mutant IDH2 acute myeloid leukemia (AML). During the
      first study of enasidenib in humans, a minority of patients with advanced myeloid
      neoplasms experienced unexpected signs/symptoms of a differentiation syndrome
      (DS), a potentially lethal entity. Objective: To characterize IDH-inhibitor
      associated DS (IDH-DS) and its effective management. Design, Setting, and
      Participants: Using data obtained from a multicenter, open-label, pivotal phase
      1/2 study of enasidenib, a differentiation syndrome review committee
      retrospectively evaluated potential cases of IDH-DS in enasidenib-treated
      patients with R/R AML. Data were collected between August 27, 2013, and October
      14, 2016. The committee identified and agreed on signs and symptoms
      characteristic of IDH-DS and developed an algorithm for identification and
      treatment. Among 281 patients with R/R AML enrolled in the trial, the committee
      identified 72 patients for review based on investigator-reported cases of DS (n =
      33) or reported adverse events or signs and symptoms characteristic of IDH-DS.
      Interventions: Treatment with enasidenib at a dosage of 50 to 650 mg/d was
      evaluated during the dose-escalation phase, and a dosage of 100 mg/d was used in
      the phase 1 expansion and phase 2, all in continual 28-day cycles. Main Outcomes
      and Measures: Unexpected adverse events of IDH-DS during the phase 1/2 study.
      Results: Thirty-three of the 281 patients (11.7%) were identified as having
      possible or probable IDH-DS. Median age of those 33 patients was 70 years (range,
      38-80 years); 20 (60.6%) were male. The most frequent manifestations were
      dyspnea, fever, pulmonary infiltrates, and hypoxia. Median time to onset was 30
      days (range, 7-129 days). Patients who experienced IDH-DS were less likely to
      have less than 20% bone marrow blasts (6% vs 22%, P = .04) and more likely to
      have undergone fewer previous anticancer regimens (median, 1.0 [range, 1-4] vs
      2.0 [range, 1-14], P = .05) at study entry than those who did not. Thirteen
      patients (39.4%) had concomitant leukocytosis. Isocitrate dehydrogenase
      differentiation syndrome was effectively managed with systemic corticosteroids.
      The enasidenib regimen was interrupted for 15 patients (45.5%), but permanent
      discontinuation of treatment was not required. Conclusions and Relevance:
      Isocitrate dehydrogenase differentiation syndrome is a recognizable and
      potentially lethal clinical entity, occurring in approximately 12% of enasidenib
      treated patients with mutant-IDH2 R/R AML. It requires prompt recognition and
      management. As use of mutant IDH inhibitors increases, these findings and
      recommendations are increasingly germane to care of patients with mutant-IDH
      neoplasms. Trial Registration: clinicaltrials.gov Identifier: NCT01915498.

PMID- 29346479
TI  - A karyozoic phenomenon for Neospora caninum.

PMID- 29346480
TI  - Changing Collective Social Norms in Favour of Reduced Harmful Use of Alcohol: A
      Review of Reviews.
AB  - Background: Public sector bodies have called for policies and programmes to shift
      collective social norms in disfavour of the harmful use of alcohol. This article
      aims to identify and summarize the evidence and propose how policies and
      programmes to shift social norms could be implemented and evaluated. Design:
      Review of reviews for all years to July 2017. Data sources: Searches on OVID
      Medline, Healthstar, Embase, PsycINFO, AMED, Social Work Abstracts, CAB
      Abstracts, Mental Measurements Yearbook, Joanna Briggs Institute EBP, Health and
      Psychosocial Instruments, International Pharmaceutical Abstracts, International
      Political Science Abstracts, NASW Clinical Register and Epub Ahead of Print
      databases. Eligibility: All reviews, without language or date restrictions
      resulting from combining the terms ((review or literature review or review
      literature or data pooling or comparative study or systematic review or meta
      analysis or pooled analysis) and (social norms or culture) and (alcohol
      drinking)). Results: Two relevant reviews were identified. One review of
      community-based interventions found one study that demonstrated small changes in
      parental disapproval of under-age drinking. One review stressed that collective
      social norms about drinking are malleable and not uniform in any one country.
      Three factors are proposed to inform programmes: provide information about the
      consequences of the harmful use of alcohol, and their causes and distribution;
      act on groups, not individuals; and strengthen environmental laws, regulations
      and approaches. Conclusions: Purposeful policies and programmes could be
      implemented to change collective social norms in disfavour of the harmful use of
      alcohol; they should be evidence-based and fully evaluated for their impact.

PMID- 29346483
TI  - Retreat From Human Rights and Adverse Consequences for Health.

PMID- 29346484
TI  - Association of Dietary Inflammatory Potential With Colorectal Cancer Risk in Men
      and Women.
AB  - Importance: Inflammation is important in colorectal cancer development. Diet
      modulates inflammation and may thus be a crucial modifiable factor in colorectal
      cancer prevention. Objective: To examine whether proinflammatory diets are
      associated with increased colorectal cancer risk by using an empirical dietary
      inflammatory pattern (EDIP) score based on a weighted sum of 18 food groups that
      characterizes dietary inflammatory potential based on circulating levels of
      inflammation biomarkers. Design, Settings, and Participants: Cohort study of 46
      804 men (Health Professionals Follow-up Study: 1986-2012) and 74 246 women
      (Nurses' Health Study: 1984-2012) followed for 26 years to examine associations
      between EDIP scores and colorectal cancer risk using Cox regression. We also
      examined associations in categories of alcohol intake and body weight. Data
      analysis began January 17, 2017, and was completed August 9, 2017. Exposures:
      EDIP scores calculated from food frequency questionnaires administered every 4
      years. Main Outcomes and Measures: Incident colorectal cancer. Results: We
      documented 2699 incident colorectal cancer cases over 2 571 831 person-years of
      follow-up. Compared with participants in the lowest EDIP quintile (Q) who had a
      colorectal cancer incidence rate (per 100 000 person-years) of 113 (men) and 80
      (women), those in the highest Q had an incidence rate of 151 (men) and 92
      (women), leading to an unadjusted rate difference of 38 and 12 more colorectal
      cancer cases, respectively, among those consuming highly proinflammatory diets.
      Comparing participants in the highest vs lowest EDIP Qs in multivariable-adjusted
      analyses, higher EDIP scores were associated with 44% (men: hazard ratio [HR],
      1.44; 95% CI, 1.19-1.74; P < .001 for trend), 22% (women: HR, 1.22; 95% CI, 1.02
      1.45; P = .007 for trend), and 32% (men and women: pooled HR, 1.32; 95% CI, 1.12
      1.55; P < .001 for trend) higher risk of developing colorectal cancer. In both
      men and women, associations were observed in all anatomic subsites except for the
      rectum in women. In subgroups (P <= .02 for all interactions), associations
      differed by alcohol intake level, with stronger associations among men (Q5 vs Q1
      HR, 1.62; 95% CI, 1.05-2.49; P = .002 for trend) and women (Q5 vs Q1 HR, 1.33;
      95% CI, 0.97-1.81; P = .03 for trend) not consuming alcohol; and by body weight,
      with stronger associations among overweight/obese men (Q5 vs Q1 HR, 1.48; 95% CI,
      1.12-1.94; P = .008 for trend) and lean women (Q5 vs Q1 HR, 1.31; 95% CI, 0.99
      1.74; P = .01 for trend). Conclusions and Relevance: Findings suggest that
      inflammation is a potential mechanism linking dietary patterns and colorectal
      cancer development. Interventions to reduce the adverse role of proinflammatory
      diets may be more effective among overweight/obese men and lean women or men and
      women who do not consume alcohol.

PMID- 29346485
TI  - Adverse Events in Facial Implant Surgery and Associated Malpractice Litigation.
AB  - Importance: Facial implants represent an important strategy for providing instant
      and long-lasting volume enhancement to address both aging and posttraumatic
      defects. Objective: To better understand risks of facial implants by examining
      national resources encompassing adverse events and considerations facilitating
      associated litigation. Design, Setting, and Participants: A cross-sectional study
      reviewed complications following facial implants. The procedures reviewed were
      performed on patients at locations throughout the United States from January 2006
      to December 2016. Data collection was completed in March 2017. The Manufacturer
      and User Facility Device Experience database, which contains medical device
      reports submitted to the US Food and Drug Administration (FDA), was searched for
      complications that occurred from January 2006 to December 2016 involving facial
      implants made by Implantech, MEDPOR, Stryker, KLS Martin, and Synthes.
      Furthermore, the Thomson Reuters Westlaw legal database was searched for relevant
      litigation. Main Outcomes and Measures: The complications of facial implants were
      analyzed in relation to the location of implant and severity of complication.
      Litigation was analyzed to determine which factors determine outcome. Results:
      Thirty-nine instances of adverse events reported to the FDA were identified.
      Sixteen (41%) involved malar implants, followed by 12 chin implants (31%). The
      most common complications included infection (18 [46%]), implant migration (9
      [23%]), swelling (7 [18%]), and extrusion (4 [10%]). Thirty-two patients (83%)
      had to have their implants removed. Infection occurred at a mean (SD) of 83.3
      (68.8) days following the surgery. One-third of complications involved either
      migration or extrusion. The mean (range) time to migration or extrusion was 381.1
      (10-2400) days. In 12 malpractice cases identified in publicly available court
      proceedings, alleged inadequate informed consent and requiring additional
      surgical intervention (ie, removal) were the most commonly cited factors.
      Conclusions and Relevance: Infection and implant migration or extrusion are the
      most common complications of facial implants. Most of these complications
      necessitate removal. These considerations need to be discussed with patients
      preoperatively as part of the informed consent process, as allegedly inadequate
      informed consent was cited in a significant proportion of resultant litigation,
      and there were overlapping considerations among adverse events reported to the
      FDA and factors brought up in relevant litigation. Cases resolved with
      settlements and jury-awarded damages encompassed considerable award totals. Level
      of Evidence: NA.

PMID- 29346486
TI  - Treatment Outcomes and Adverse Events Following In-Office Angiolytic Laser With
      or Without Concurrent Polypectomy for Vocal Fold Polyps.
AB  - Importance: In-office angiolytic laser procedures have been used successfully as
      an alternative treatment for vocal fold polyps; little is known in detail about
      the treatment outcomes and adverse events. Objective: To examine the outcomes and
      incidence rates of adverse events associated with in-office angiolytic laser
      procedures with or without concurrent polypectomy as an alternative treatment for
      vocal fold polyps. Design, Setting, and Participants: Retrospective cohort study
      at a tertiary medical center. We identified 114 consecutive patients with vocal
      polyps who underwent in-office angiolytic laser treatments between January 1,
      2014, and August 31, 2016. After the exclusion of 17 with missing or incomplete
      data, 97 were enrolled. Interventions: In-office 532-nm laser procedures with or
      without concurrent polypectomy. Main Outcomes and Measures: Between 1 and 2
      months after the surgical procedures, we collected the following outcome data:
      videolaryngostroboscopy, perceptual rating of voice quality, acoustic analysis,
      maximal phonation time, and subjective rating of voice quality using a visual
      analogue scale and 10-item voice handicap index. Results: This study enrolled 97
      patients (mean [SD] age, 45.6 [11.3] years; 48 [49%] male). The mean duration of
      symptoms was 10.1 months (range, 1-60 months). Twenty-nine patients (30%) had
      angiolytic laser procedures only, while 68 (70%) received laser with concurrent
      polypectomy. Both treatment modalities offered significant improvements. Only 1
      patient (1%) receiving angiolytic laser with concurrent polypectomy underwent
      another treatment session, so this group had significantly less need for multiple
      treatments than those receiving laser treatment alone (6 [21%]; effect size, 
      1.57; 95% CI, -2.77 to -0.36). We identified 8 adverse events (8% of the cases):
      vocal fold edema (n = 5), vocal hematoma (n = 2), and vocal ulceration (n = 1).
      Patients treated with laser plus concurrent polypectomy had significantly fewer
      adverse events than those treated with angiolytic laser alone (2 [3%] vs 6 [21%];
      effect size, 1.20; 95% CI, 0.26 to 2.13). Conclusions and Relevance: In-office
      angiolytic laser procedures can be an effective alternative treatment for vocal
      polyps, although with possible need for multiple treatment sessions and
      occasional occurrence of minor postoperative adverse events. Concurrent
      polypectomy following laser coagulation allows less laser energy delivery and
      reduces the risk of postoperative adverse events and the need for additional
      treatment sessions.

PMID- 29346487
TI  - Preoperative Evaluations for Cataract Surgery Are Routine but Anachronistic.

PMID- 29346488
TI  - A Subretinal Cell Delivery Method via Suprachoroidal Access in Minipigs: Safety
      and Surgical Outcomes.
AB  - Purpose: This study evaluated a new subretinal method for delivery of human or
      pig umbilical tissue-derived cells (hUTC or pUTC, respectively) using a novel
      subretinal injection cannula and suprachoroidal approach in Gottingen minipig
      eyes. hUTC (palucorcel) are currently under development for treating geographic
      atrophy in humans. Methods: Twenty-four Gottingen minipigs (divided into eight
      groups) were subretinally administered palucorcel, pUTC, or vehicle. In some
      cases, fluorescently labeled cells and vehicle were administered. Conjunctival
      cutdown and sclerotomy were performed, then a flexible cannula containing a
      microneedle was inserted and advanced into the suprachoroidal space. The
      microneedle was deployed and visualized; 50 MUL cells (target concentration, 11.2
      * 106 cells/mL [560,000 cells/eye]) or vehicle was injected subretinally. Safety
      outcomes were evaluated. Results: For all animals, cells and vehicle were
      successfully administered. Labeled cells or fluorescent vehicle were contained in
      the subretinal bleb, without leakage into the vitreous. No retinal detachment or
      vitreous traction band was identified by ophthalmologic examination. At all time
      points, observed microscopic changes were attributable to experimental
      procedures. On histopathology immediately after injection, localized retinal
      detachments were seen, along with focal retinal, choroidal, and/or scleral
      discontinuities. A moderate inflammatory response was seen in a limited number of
      animals. In the allogeneic setting, no antibody responses were detectable. Anti
      human UTC antibodies were detected in the xenogeneic setting. Conclusions:
      Palucorcel, pUTC, and vehicle were successfully administered to Gottingen
      minipigs using a novel subretinal injection cannula via a suprachoroidal surgical
      approach, with no significant adverse events; therefore, this technique appears
      to be feasible for further clinical development.

PMID- 29346489
TI  - The Suprachoroidal Delivery Route and Exploring the Potential of Cell-Based
      Therapies for Age-Related Macular Degeneration.

PMID- 29346491
TI  - Increased mtDNA Copy Number Does Not Protect Against LHON.

PMID- 29346490
TI  - Composition, Architecture, and Functional Implications of the Connective Tissue
      Network of the Extraocular Muscles.
AB  - Purpose: We examined the pattern and extent of connective tissue distribution in
      the extraocular muscles (EOMs) and determined the ability of the interconnected
      connective tissues to disseminate force laterally. Methods: Human EOMs were
      examined for collagens I, III, IV, and VI; fibronectin; laminin; and elastin
      using immunohistochemistry. Connective tissue distribution was examined with
      scanning electron microscopy. Rabbit EOMs were examined for levels of force
      transmission longitudinally and transversely using in vitro force assessment.
      Results: Collagens I, III, and VI localized to the endomysium, perimysium, and
      epimysium. Collagen IV, fibronectin, and laminin localized to the basal lamina
      surrounding all myofibers. All collagens localized similarly in the orbital and
      global layers throughout the muscle length. Elastin had the most irregular
      pattern and ran longitudinally and circumferentially throughout the length of all
      EOMs. Scanning electron microscopy showed these elements to be extensively
      interconnected, from endomysium through the perimysium to the epimysium
      surrounding the whole muscle. In vitro physiology demonstrated force generation
      in the lateral dimension, presumably through myofascial transmission, which was
      always proportional to the force generated in the longitudinally oriented
      muscles. Conclusions: A striking connective tissue matrix interconnects all the
      myofibers and extends, via perimysial connections, to the epimysium. These
      interconnections are significant and allow measurable force transmission
      laterally as well as longitudinally, suggesting that they may contribute to the
      nonlinear force summation seen in motor unit recording studies. This provides
      strong evidence that separate compartmental movements are unlikely as no region
      is independent of the rest of the muscle.

PMID- 29346492
TI  - Author Response: Increased mtDNA Copy Number Protects Against LHON.

PMID- 29346495
TI  - Long Term Temporal Changes in Structure and Function of Rat Visual System After
      Blast Exposure.
AB  - Purpose: We identify long-term ocular sequelae subsequent to experimental blast
      exposure. Methods: Male Long-Evans rats were exposed to 230 kPa side-on primary
      blast overpressure using a compressed air driven shock tube. Visual system
      function and structure were assessed for 8 weeks after exposure using optokinetic
      nystagmus and optical coherence tomography. Vitreous protein expression and
      histology (TUNEL, H&E) were performed at 1 day and 1, 4, and 8 weeks. IOP was
      recorded bilaterally during blast in a subset of animals. Results: Blast pressure
      profiles resembled the Friedlander waveform indicative of an open field blast.
      Peak IOP in directly-exposed eyes (240 kPa) was similar to peak blast
      overpressure, but IOP in indirectly-exposed eyes was 30% lower. Contrast
      sensitivity of blast-exposed animals decreased significantly by 20% 1 day after
      blast and did not recover by 8 weeks. Significant swelling and structural damage
      to the corneal epithelial and stromal layers were observed 2 weeks after blast
      exposure. Swollen corneas increased 254 +/- 143 MUm from baseline by 6 weeks, and
      scarring developed by 8 weeks. Histology revealed additional lens pathology 1
      week after blast, suggestive of cataract development. Endothelial cell density
      increased significantly in blast-exposed animals between 1 and 4 weeks.
      Neurofilament heavy chain significantly increased after blast and returned to
      near baseline values by 8 weeks. Inflammatory cytokine changes corroborated
      ocular pathology findings. Conclusions: These data demonstrate immediate visual
      dysfunction and biochemical responses, but delayed structural pathology, in
      response to single primary blast exposure. The delayed pathology time course may
      provide a window to implement treatment strategies for improved visual outcome.

PMID- 29346493
TI  - Antimicrobial Studies Using the Therapeutic Tissue Cross-Linking Agent, Sodium
      Hydroxymethylglycinate: Implication for Treating Infectious Keratitis.
AB  - Purpose: Our recent studies raise the possibility of using sodium
      hydroxymethylglycinate (SMG), for pharmacologic therapeutic tissue cross-linking
      (TXL) of the cornea. The present study was performed to evaluate the
      antimicrobial effects of SMG for potential use in treating infectious keratitis.
      Methods: In initial (group 1) experiments, methicillin-sensitive Staphylococcus
      aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), and
      Pseudomonas aeruginosa (PA) were treated with SMG (10-40 mM) for 10 to 120
      minutes. In group 2 experiments, MRSA, PA, Candida albicans (CA), and vancomycin
      resistant Enterococcus (VRE) were treated with SMG (20-200 mM) for 30 minutes. In
      group 2 experiments, BSA and neutralizing buffer were added to provide a
      proteinaceous medium, and to ensure precise control of SMG exposure times,
      respectively. SMG effectiveness was quantitated based on pathogen growth
      following a 24- to 48-hour incubation period. Results: In group 1 experiments, as
      expected, time- and concentration-dependent bactericidal effects were noted using
      MSSA. In addition, the effect of SMG (40 mM) was greatest against MSSA (99.3%),
      MRSA (96.0%), and PA (97.4%) following a 2-hour exposure with lesser effects
      following 30- and 10-minute exposures. In group 2 experiments, concentration
      dependent bactericidal effects were confirmed for MRSA (91%), PA (99%), and VRE
      (55%) for 200-mM SMG with 30-minute treatment. SMG was not as effective against
      CA, with a maximum kill rate of 37% at 80 mM SMG. Conclusions: SMG solution
      exhibits a dose-dependent bactericidal effect on MSSA, MRSA, and PA, with milder
      effects on VRE and CA. These studies raise the possibility of using SMG TXL for
      the treatment of infectious keratitis.

PMID- 29346496
TI  - Melanopsin System Dysfunction in Smith-Magenis Syndrome Patients.
AB  - Purpose: Smith-Magenis syndrome (SMS) causes sleep disturbance that is related to
      an abnormal melatonin profile. It is not clear how the genomic disorder leads to
      a disturbed synchronization of the sleep/wake rhythm in SMS patients. To evaluate
      the integrity of the intrinsically photosensitive retinal ganglion cell
      (ipRGC)/melanopsin system, the transducers of the light-inhibitory effect on
      pineal melatonin synthesis, we recorded pupillary light responses (PLR) in SMS
      patients. Methods: Subjects were SMS patients (n = 5), with molecular diagnosis
      and melatonin levels measured for 24 hours and healthy controls (n = 4). Visual
      stimuli were 1-second red light flashes (640 nm; insignificant direct ipRGC
      activation), followed by a 470-nm blue light, near the melanopsin peak absorption
      region (direct ipRGC activation). Blue flashes produce a sustained pupillary
      constriction (ipRGC driven) followed by baseline return, while red flashes
      produce faster recovery. Results: Pupillary light responses to 640-nm red flash
      were normal in SMS patients. In response to 470-nm blue flash, SMS patients had
      altered sustained responses shown by faster recovery to baseline. SMS patients
      showed impairment in the expected melatonin production suppression during the
      day, confirming previous reports. Conclusions: SMS patients show dysfunction in
      the sustained component of the PLR to blue light. It could explain their well
      known abnormal melatonin profile and elevated circulating melatonin levels during
      the day. Synchronization of daily melatonin profile and its photoinhibition are
      dependent on the activation of melanopsin. This retinal dysfunction might be
      related to a deficit in melanopsin-based photoreception, but a deficit in rod
      function is also possible.

PMID- 29346494
TI  - Novel Myopia Genes and Pathways Identified From Syndromic Forms of Myopia.
AB  - Purpose: To test the hypothesis that genes known to cause clinical syndromes
      featuring myopia also harbor polymorphisms contributing to nonsyndromic
      refractive errors. Methods: Clinical phenotypes and syndromes that have
      refractive errors as a recognized feature were identified using the Online
      Mendelian Inheritance in Man (OMIM) database. One hundred fifty-four unique
      causative genes were identified, of which 119 were specifically linked with
      myopia and 114 represented syndromic myopia (i.e., myopia and at least one other
      clinical feature). Myopia was the only refractive error listed for 98 genes and
      hyperopia and the only refractive error noted for 28 genes, with the remaining 28
      genes linked to phenotypes with multiple forms of refractive error. Pathway
      analysis was carried out to find biological processes overrepresented within
      these sets of genes. Genetic variants located within 50 kb of the 119 myopia
      related genes were evaluated for involvement in refractive error by analysis of
      summary statistics from genome-wide association studies (GWAS) conducted by the
      CREAM Consortium and 23andMe, using both single-marker and gene-based tests.
      Results: Pathway analysis identified several biological processes already
      implicated in refractive error development through prior GWAS analyses and animal
      studies, including extracellular matrix remodeling, focal adhesion, and axon
      guidance, supporting the research hypothesis. Novel pathways also implicated in
      myopia development included mannosylation, glycosylation, lens development,
      gliogenesis, and Schwann cell differentiation. Hyperopia was found to be linked
      to a different pattern of biological processes, mostly related to organogenesis.
      Comparison with GWAS findings further confirmed that syndromic myopia genes were
      enriched for genetic variants that influence refractive errors in the general
      population. Gene-based analyses implicated 21 novel candidate myopia genes
      (ADAMTS18, ADAMTS2, ADAMTSL4, AGK, ALDH18A1, ASXL1, COL4A1, COL9A2, ERBB3, FBN1,
      GJA1, GNPTG, IFIH1, KIF11, LTBP2, OCA2, POLR3B, POMT1, PTPN11, TFAP2A, ZNF469).
      Conclusions: Common genetic variants within or nearby genes that cause syndromic
      myopia are enriched for variants that cause nonsyndromic, common myopia. Analysis
      of syndromic forms of refractive errors can provide new insights into the
      etiology of myopia and additional potential targets for therapeutic
      interventions.

PMID- 29346497
TI  - Convergent and Divergent Validity of the Grammaticality and Utterance Length
      Instrument.
AB  - Purpose: This feasibility study examines the convergent and divergent validity of
      the Grammaticality and Utterance Length Instrument (GLi), a tool designed to
      assess the grammaticality and average utterance length of a child's prerecorded
      story retell. Method: Three raters used the GLi to rate audio-recorded story
      retells from 100 English-speaking preschool children. To examine convergent
      validity, the results of the GLi were correlated with 2 language sample measures,
      mean length of utterance in words and percentage of grammatical utterances, and
      with the results of the Structured Photographic Expressive Language Test-Third
      Edition (Dawson, Stout, & Eyer, 2003). To examine divergent validity, the results
      of the GLi were correlated with the results of the Kaufman Brief Intelligence
      Test-Second Edition (Kaufman & Kaufman, 2004). Comparisons between task
      completion time for the GLi and Systematic Analysis of Language Transcripts
      (SALT; Miller & Iglesias, 2010) transcription and analysis were also conducted.
      Last, preliminary discriminant analysis was used to examine the diagnostic
      potential of the GLi. Results: The results of this study provide evidence of
      convergent and divergent validity for the GLi. The task completion time for the
      GLi was considerably shorter than the SALT transcription and analysis.
      Preliminary analysis of diagnostic accuracy suggests that the GLi has the
      potential to be a good tool to identify children with language impairment.
      Discussion: The GLi has good convergent and divergent validity and is a reliable
      instrument to assess utterance length and grammaticality of prerecorded language
      samples. However, SALT transcription and analysis provide a more detailed and
      comprehensive analysis of the language skills of a child.

PMID- 29346498
TI  - Association of Treatment for Hodgkin Lymphoma With Estrogen Receptor Status of
      Subsequent Breast Cancers.

PMID- 29346499
TI  - Repeatability and Agreement of Visual Acuity Using the ETDRS Number Chart,
      Landolt C Chart, or ETDRS Alphabet Chart in Eyes With or Without Sight
      Threatening Diseases.
AB  - Importance: The Early Treatment Diabetic Retinopathy Study (ETDRS) alphabet chart
      is not feasible for measuring best-corrected visual acuity (BCVA) for individuals
      who are unfamiliar with the Roman alphabet. The ETDRS Landolt C chart is an
      alternative, but it may not reflect true BCVA among those with confusion between
      left and right. The ETDRS number chart might overcome these limitations, but
      little is known regarding its reliability. Objective: To evaluate repeatability
      and agreement of BCVA using the ETDRS number chart or Landolt C chart compared
      with ETDRS alphabet charts in healthy and diseased eyes. Design, Setting, and
      Participants: A cross-sectional study was conducted in Thailand from July 1,
      2015, to June 30, 2016, among 154 adult Thai individuals. Those who could read
      Roman alphabets were classified into the following 4 groups, using 1 eye per
      participant: group A, which comprised 60 healthy eyes (BCVA, 20/20-20/25); group
      B, which comprised 40 eyes with age-related cataract, diabetic macular edema, or
      age-related macular degeneration (BCVA, 20/20-20/40); group C, which comprised 40
      eyes with age-related cataract, diabetic macular edema, or age-related macular
      degeneration (BCVA, 20/50-20/100); and group D, which comprised 14 eyes with age
      related cataract, diabetic macular edema, or age-related macular degeneration
      (BCVA, 20/125-20/200). Interventions: Two standardized 4-m BCVA measurements with
      3 different Precision Vision ETDRS charts (PV number, Landolt C, and alphabet),
      in random sequence, performed 30 minutes apart. Main Outcomes and Measures:
      Repeatability, agreement, and testing duration of BCVA. Results: Of 154 Thai
      participants (82 women and 72 men; mean [SD] age, 52.9 [18.2] years), the ETDRS
      number chart had strong repeatability coefficients (group A, 0.61 [95% CI, 0.42
      0.75]; group B, 0.87 [95% CI, 0.78-0.93]; group C, 0.81 [95% CI, 0.67-0.90]; and
      group D, 0.81 [95% CI, 0.49-0.94]). Concordance correlation coefficients between
      the number and alphabet charts were also strong (group A, 0.89 [95% CI, 0.82
      0.93]; group B, 0.97 [95% CI, 0.94-0.98]; group C, 0.92 [95% CI, 0.86-0.96]; and
      group D, 0.96 [95% CI, 0.87-0.99]), while the concordance correlation
      coefficients between the Landolt C and alphabet charts were lower (group A, 0.72
      [95% CI, 0.52-0.83]; group B, 0.83 [95% CI, 0.68-0.91]; group C, 0.79 [95% CI,
      0.61-0.89]; and group D, 0.89 [95% CI, 0.66-0.97]). The mean letter score
      difference between the number and alphabet charts was 1 (95% limits of agreement,
      -4 to +6) compared with -7 (95% limits of agreement, -18 to +5; P < .001) between
      the Landolt C and alphabet charts. Conclusions and Relevance: The repeatability
      coefficients and concordance correlation coefficients suggest that ETDRS number
      charts are viable for measuring BCVA in clinical practice and trials for
      individuals who are unfamiliar with the Roman alphabet.

PMID- 29346500
TI  - Commentary: Alcohol and Alcoholism Special Issue on 'Alcohol and Liver
      Transplantation'.

PMID- 29346503
TI  - p53beta: a new prognostic marker for patients with clear-cell renal cell
      carcinoma from 5.3 years of median follow-up.
AB  - We previously reported six different p53 isoforms in renal cell carcinoma (RCC).
      In the present study, influences of p53beta on recurrence-free survival (RFS) and
      overall survival (OS) were evaluated. Patients diagnosed with RCC in our center
      were into this study. mRNA expressions of p53 isoforms (p53alpha, p53beta,
      p53gamma) in tumors were determined by RT-PCR and real-time PCR. Functional yeast
      based assay was performed to analyze p53 mutational status. p53beta transfected
      786-O and CAKi-1 cells were cultured to examine expressions of B-cell lymphoma 2
      associated X protein (bax) and caspase-3, and ratios of apoptosis. After
      surgeries, all patients were followed up at programmed intervals. 266 patients
      were analyzed in this study. Median follow-up time was 5.3 years. RT-PCR (r = 
      0.72, P = 0.016) and real-time PCR (r = -0.65, P = 0.033) both showed only
      p53beta expressed higher level in lower tumor stage versus higher stage. p53 wild
      type and p53 mutation had comparable RFS (P = 0.361) and OS (P = 0.218),
      respectively. Kaplan-Meier analysis showed high p53beta expression was associated
      with significantly improved RFS and OS, regardless of p53 mutational status. High
      p53beta expression indicated better RFS [hazard ratio (HR) 2.599, 95% confidence
      interval (CI) 1.472-4.551, P = 0.038] and OS (HR 2.604, 95% CI 1.453-4.824, P =
      0.031). p53beta transfected 786-O and CAKi-1 cells expressed significantly higher
      level of bax and caspase-3, and had higher ratios of apoptosis than untransfected
      cells. Taken together, higher level of p53beta predict better prognosis in
      patients with RCC through enhancing apoptosis in tumors.

PMID- 29346505
TI  - Clustering single cells: a review of approaches on high-and low-depth single-cell
      RNA-seq data.

PMID- 29346504
TI  - BAUM: improving genome assembly by adaptive unique mapping and local overlap
      layout-consensus approach.
AB  - Motivation: It is highly desirable to assemble genomes of high continuity and
      consistency at low cost. The current bottleneck of draft genome continuity using
      the second generation sequencing (SGS) reads is primarily caused by uncertainty
      among repetitive sequences. Even though the single-molecule real-time sequencing
      technology is very promising to overcome the uncertainty issue, its relatively
      high cost and error rate add burden on budget or computation. Many long-read
      assemblers take the overlap-layout-consensus (OLC) paradigm, which is less
      sensitive to sequencing errors, heterozygosity and variability of coverage.
      However, current assemblers of SGS data do not sufficiently take advantage of the
      OLC approach. Results: Aiming at minimizing uncertainty, the proposed method
      BAUM, breaks the whole genome into regions by adaptive unique mapping; then the
      local OLC is used to assemble each region in parallel. BAUM can (i) perform
      reference-assisted assembly based on the genome of a close species (ii) or
      improve the results of existing assemblies that are obtained based on short or
      long sequencing reads. The tests on two eukaryote genomes, a wild rice Oryza
      longistaminata and a parrot Melopsittacus undulatus, show that BAUM achieved
      substantial improvement on genome size and continuity. Besides, BAUM
      reconstructed a considerable amount of repetitive regions that failed to be
      assembled by existing short read assemblers. We also propose statistical
      approaches to control the uncertainty in different steps of BAUM. Availability
      and implementation:
      http://www.zhanyuwang.xin/wordpress/index.php/2017/07/21/baum. Supplementary
      information: Supplementary data are available at Bioinformatics online.

PMID- 29346506
TI  - Small and surrounded: population size and land use intensity interact to
      determine reliance on autonomous selfing in a monocarpic plant.
AB  - Background and Aims: Habitat fragmentation has transformed landscapes globally,
      leaving remnants embedded within a complex matrix that is rapidly becoming more
      developed. For many plant populations, the associated factors of decreased size
      and intensification of land use surrounding them are expected to increase pollen
      limitation ('PL'), unless autonomous self-pollination provides reproductive
      assurance ('RA'). Decreased pollinator visitation is often assumed to drive these
      patterns, but other, less studied mechanisms might include increased
      heterospecific pollen transfer or decreased conspecific pollen availability via
      florivory. I investigate how PL and RA and their potential underlying mechanisms
      vary with population size and land use intensity surrounding populations in the
      biennial Sabatia angularis (Gentianaceae). Methods: I estimated the capacity for
      seed production via autonomous self-pollination (i.e. autofertility). Over 2
      years in 22 S. angularis populations across a fragmented landscape, I performed
      emasculation and pollen supplementation experiments measuring RA and PL, and
      quantified visitation rates of potential pollinators and a pollen consumer,
      conspecific pollen loads and rates of heterospecific pollen deposition. Key
      results: Autofertility based on fruit mass was 93 % under PL but only 51.6 %
      relative to maximal conditions. PL and RA were significant on average across
      populations in the first year of study. Variation in RA was significantly
      influenced by the interaction between population size and land use intensity,
      which in turn rendered PL independent of these factors. Visitation and
      heterospecific pollen deposition rates were greatest in small populations and
      declined with population size, while conspecific pollen loads were greatest in
      intermediate sized populations. Conclusions: Increased reliance on RA is
      predicted in small S. angularis populations surrounded by intense development,
      which can explain elevated selfing rates in fragmented populations of plant
      species more generally. Results from this study point toward forces such as
      heterospecific pollen transfer, self-pollen limitation or resource availability
      influencing the need and ability to rely on RA.

PMID- 29346508
TI  - Oroxylin A, a natural compound, mitigates the negative effects of TNFalpha
      treated acute myelogenous leukemia cells.
AB  - Tumor necrosis factor alpha (TNFalpha) is a complicated cytokine which is
      involved in proliferation and differentiation of acute myelogenous leukemia (AML)
      cells through a poorly understood mechanism. Mechanistic studies indicate that
      TNFalpha induced binding of PI3K subunit p85alpha to N-terminal truncated nuclear
      receptor RXRalpha (tRXRalpha) proteins, and activated AKT. The activated PI3K/AKT
      pathway negatively regulated differentiation of AML cells through the
      upregulation of c-Myc. In addition, TNFalpha also induced activation of nuclear
      factor kappaB (NF-kappaB), a nuclear transcription factor which was shown to
      promote cell proliferation. The present study demonstrates that oroxylin A, a
      natural compound isolated from Scutellariae radix, sensitizes leukemia cells to
      TNFalpha and markedly enhances TNFalpha-induced growth inhibition and
      differentiation of AML cell including human leukemia cell lines and primary AML
      cells. Activation of PI3K/AKT pathway could be inhibited by oroxylin A through
      inhibiting expression of tRXRalpha in NB4 and HL-60-resistant cells. Furthermore,
      we found that oroxylin A inhibited the activation of NF-kappaB and the DNA
      binding activity by TNFalpha proved by EMSA in these two AML cell lines.
      Moreover, in vivo studies showed that treatment with oroxylin A in combination
      with TNFalpha decreased AML cell population and prolonged survival in NOD/SCID
      mice with xenografts of primary AML cells. Overall, our results indicate that
      oroxylin A is able to inhibit the negative effects of TNFalpha for AML therapy,
      suggesting that combination of oroxylin A and TNFalpha have the potential to
      delay growth or eliminate the abnormal leukemic cells, thus representing a
      promising strategy for AML treatment.

PMID- 29346509
TI  - A distance-based approach for testing the mediation effect of the human
      microbiome.
AB  - Motivation: Recent studies have revealed a complex interplay between environment,
      the human microbiome and health and disease. Mediation analysis of the human
      microbiome in these complex relationships could potentially provide insights into
      the role of the microbiome in the etiology of disease and, more importantly, lead
      to novel clinical interventions by modulating the microbiome. However, due to the
      high dimensionality, sparsity, non-normality and phylogenetic structure of
      microbiome data, none of the existing methods are suitable for testing such
      clinically important mediation effect. Results: We propose a distance-based
      approach for testing the mediation effect of the human microbiome. In the
      framework, the nonlinear relationship between the human microbiome and
      independent/dependent variables is captured implicitly through the use of sample
      wise ecological distances, and the phylogenetic tree information is conveniently
      incorporated by using phylogeny-based distance metrics. Multiple distance metrics
      are utilized to maximize the power to detect various types of mediation effect.
      Simulation studies demonstrate that our method has correct Type I error control,
      and is robust and powerful under various mediation models. Application to a real
      gut microbiome dataset revealed that the association between the dietary fiber
      intake and body mass index was mediated by the gut microbiome. Availability and
      implementation: An R package 'MedTest' is freely available at
      https://github.com/jchen1981/MedTest. Contact: zhiwei@njit.edu or
      chen.jun2@mayo.edu. Supplementary information: Supplementary data are available
      at Bioinformatics online.

PMID- 29346507
TI  - Activity and safety of afatinib in a window preoperative EORTC study in patients
      with squamous cell carcinoma of the head and neck (SCCHN).
AB  - Background: To investigate the activity and safety of afatinib in the
      preoperative treatment of squamous cell carcinoma of the head and neck (SCCHN).
      Patients and methods: This study was an open-label, randomized, multicenter,
      phase II window of opportunity trial. Treatment-naive SCCHN patients selected for
      primary curative surgery were randomized (5 : 1 ratio) to receive afatinib during
      14 days (day -15 until day -1) before surgery (day 0) or no treatment. Tumor
      biopsies, 2-[fluorine-18]-fluoro-2-deoxy-d-glucose positron emission tomography
      (FDG-PET), and magnetic resonance imaging (MRI) were carried out at diagnosis and
      just before surgery. The primary end point was metabolic FDG-PET response
      (according to EORTC guidelines). Other end points included response assessment
      based on the Response Evaluation Criteria In Solid Tumors (RECIST) v1.1, dynamic
      contrast-enhanced (DCE)-MRI, diffusion weighted (DW)-MRI, safety, and
      translational research (TR). Results: Thirty patients were randomized: 25 to
      afatinib and 5 to control arm. Of the 23 eligible patients randomized to
      afatinib, 16 (70%; 95% CI: 47% to 87%) patients had a partial metabolic FDG-PET
      response (PMR). Five patients (22%; 95% CI: 8% to 44%) showed a partial response
      by RECISTv1.1. Responses assessed via DCE-MRI and DWI-MRI did not show a strong
      association with PMR or RECIST. One patient discontinued afatinib after 11 days
      for grade 3 diarrhea with subsequent renal failure and 24 days delay in surgery.
      No grade 4 toxicities or surgical comorbidities related to afatinib were
      reported. TR results indicated that PMR was more frequent in the tumors with high
      Cluster3-hypoxia score expression and with TP53 wild type. Conclusion: Afatinib
      given for 2 weeks to newly diagnosed SCCHN patients induces a high rate of FDG
      PET partial metabolic response and partial response according to RECISTv1.1.
      Afatinib can be safely administered before surgery. Although exploratory, the
      hypoxic gene signature needs further investigations as a predictive biomarker of
      afatinib activity. Clinical trial registration: ClinicalTrials.gov: NCT01538381.

PMID- 29346510
TI  - VIPER: a web application for rapid expert review of variant calls.
AB  - Summary: With the rapid development in next-generation sequencing, cost and time
      requirements for genomic sequencing are decreasing, enabling applications in many
      areas such as cancer research. Many tools have been developed to analyze genomic
      variation ranging from single nucleotide variants to whole chromosomal
      aberrations. As sequencing throughput increases, the number of variants called by
      such tools also grows. Often employed manual inspection of such calls is thus
      becoming a time-consuming procedure. We developed the Variant InsPector and
      Expert Rating tool (VIPER) to speed up this process by integrating the
      Integrative Genomics Viewer into a web application. Analysts can then quickly
      iterate through variants, apply filters and make decisions based on the generated
      images and variant metadata. VIPER was successfully employed in analyses with
      manual inspection of more than 10 000 calls. Availability and implementation:
      VIPER is implemented in Java and Javascript and is freely available at
      https://github.com/MarWoes/viper. Contact: marius.woeste@uni-muenster.de.
      Supplementary information: Supplementary data are available at Bioinformatics
      online.

PMID- 29346511
TI  - Sleep and Health in Older Adulthood: Recent Advances and the Path Forward.

PMID- 29346512
TI  - Validation of the Pediatric Infectious Diseases Society-Infectious Diseases
      Society of America Severity Criteria in Children With Community-Acquired
      Pneumonia.
AB  - Background: The Pediatric Infectious Diseases Society (PIDS)-Infectious Diseases
      Society of America (IDSA) guideline for community-acquired pneumonia (CAP)
      recommends intensive care unit (ICU) admission or continuous monitoring for
      children meeting severity criteria. Our objective was to validate these criteria.
      Methods: This was a retrospective cohort study of children aged 3 months-18 years
      diagnosed with CAP in a pediatric emergency department (ED) from September 2014
      through August 2015. Children with chronic conditions and recent ED visits were
      excluded. The primary predictor was the PIDS-IDSA severity criteria. Outcomes
      included disposition, and interventions and diagnoses that necessitated
      hospitalization (ie, need for hospitalization [NFH]). Results: Of 518 children,
      56.6% were discharged; 54.3% of discharged patients and 80.8% of those
      hospitalized for less than 24 hours were classified as severe. Of those admitted,
      10.7% did not meet severity criteria; 69.5% met PIDS-IDSA severity criteria. Of
      those children, 73.1% did not demonstrate NFH. The areas under the receiver
      operator characteristic curves (AUC) for PIDS-IDSA major criteria were 0.63 and
      0.51 for predicting disposition and NFH, respectively. For PIDS-IDSA minor
      criteria, the AUC was 0.81 and 0.56 for predicting disposition and NFH,
      respectively. The sensitivity, specificity, and likelihood ratios (LR)+ and LR-
      of the PIDS-IDSA criteria were 89%, 46%, 1.65, and 0.23 for disposition and 95%,
      16%, 1.13, and 0.31 for NFH. Conclusions: More than half of children classified
      as severe by PIDS-IDSA criteria were not hospitalized. The PIDS-IDSA CAP severity
      criteria have only fair ability to predict the need for hospitalization. New
      predictive tools specifically for children are required to improve clinical
      decision making.

PMID- 29346513
TI  - Pancancer analysis identifies prognostic high-APOBEC1 expression level implicated
      in cancer in-frame insertions and deletions.
AB  - Genome insertions and deletions (indels) show tremendous functional impacts
      despite they are much less common than single nucleotide variants, which are at
      the center of studies assessing cancer mutational signatures. We studied 8891
      tumor samples of 32 types from The Cancer Genome Atlas in order to explore those
      genes which are potentially implicated in cancer indels. Survival analysis
      identified in-frame indels as the most important variants predicting adverse
      outcome. Transcriptome-wide association study identified 16 genes overexpressed
      in both tumor samples and tumor types with high number of in-frame indels, of
      whom four (APOBEC1, BCL2L15, FOXL1 and PDX1) were identified with gene products
      distributed within the nucleus. APOBEC1 emerged as the mere consistently
      hypomethylated gene in tumor samples with high number of in-frame indels. The
      correlation of APOBEC1 expression levels with cancer indels was independent of
      age and defects in DNA homologous recombination (HR) and/or mismatch repair.
      Unlike frame-shift indels, triplet repeat motifs were found to occur frequently
      at in-frame indel sites. The splicing variant 3, making a shorter isoform b,
      showed essentially all the same indel correlations as of APOBEC1. Expression
      levels of both APOBEC1 and variant 3 were found to be predicting adverse
      prognosis independent of DNA HR and mismatch repair. Not less importantly, high
      level of variant 3 in paired normal tissues was also proved to predict cancer
      outcome. Our findings propose APOBEC1 and isoform b as the potential endogenous
      mutators implicated in cancer in-frame indels and pave the way for their use as
      novel prognostic tumor markers.

PMID- 29346514
TI  - Optimal water networks in protein cavities with GAsol and 3D-RISM.
AB  - Motivation: Water molecules in protein binding sites play essential roles in
      biological processes. The popular 3D-RISM prediction method can calculate the
      solvent density distribution within minutes, but is difficult to convert it into
      explicit water molecules. Results: We present GAsol, a tool that is capable of
      finding the network of water molecules that best fits a particular 3D-RISM
      density distribution in a fast and accurate manner and that outperforms other
      available tools by finding the globally optimal solution thanks to its genetic
      algorithm. Availability and implementation: https://github.com/accsc/GAsol. BSD 3
      clauses license. Contact: alvaro.x.cortes@gsk.com. Supplementary information:
      Supplementary data are available at Bioinformatics online.

PMID- 29346515
TI  - A brain-based pain facilitation mechanism contributes to painful diabetic
      polyneuropathy.
AB  - The descending pain modulatory system represents one of the oldest and most
      fundamentally important neurophysiological mechanisms relevant to pain. Extensive
      work in animals and humans has shown how a functional imbalance between the
      facilitatory and inhibitory components is linked to exacerbation and maintenance
      of persistent pain states. Forward translation of these findings into clinical
      populations is needed to verify the relevance of this imbalance. Diabetic
      polyneuropathy is one of the most common causes of chronic neuropathic pain;
      however, the reason why ~25-30% of patients with diabetes develop pain is not
      known. The current study used a multimodal clinical neuroimaging approach to
      interrogate whether the sensory phenotype of painful diabetic polyneuropathy
      involves altered function of the ventrolateral periaqueductal grey-a key node of
      the descending pain modulatory system. We found that ventrolateral periaqueductal
      grey functional connectivity is altered in patients suffering from painful
      diabetic polyneuropathy; the magnitude of which is correlated to their
      spontaneous and allodynic pain as well as the magnitude of the cortical response
      elicited by an experimental tonic heat paradigm. We posit that ventrolateral
      periaqueductal grey-mediated descending pain modulatory system dysfunction may
      reflect a brain-based pain facilitation mechanism contributing to painful
      diabetic polyneuropathy.

PMID- 29346516
TI  - Deletion of Nrip1 Extends Female Mice Longevity, Increases Autophagy, and Delays
      Cell Senescence.
AB  - Using age of female sexual maturation as a biomarker, we previously identified
      nuclear receptor interacting protein 1 (Nrip1) as a candidate gene that may
      regulate aging and longevity. In the current report, we found that the deletion
      of Nrip1 can significantly extend longevity of female mice (log-rank test, p =
      .0004). We also found that Nrip1 expression is altered differently in various
      tissues during aging and under diet restriction. Remarkably, Nrip1 expression is
      elevated with aging in visceral white adipose tissue (WAT), but significantly
      reduced after 4 months of diet restriction. However, in gastrocnemius muscle,
      Nrip1 expression is significantly upregulated after the diet restriction. In
      mouse embryonic fibroblasts, we found that the deletion of Nrip1 can suppress
      fibroblast proliferation, enhance autophagy under normal culture or amino acid
      starvation conditions, as well as delay oxidative and replicative senescence.
      Importantly, in WAT of old animals, the deletion of the Nrip could significantly
      upregulate autophagy and reduce the number of senescent cells. These results
      suggest that deleting Nrip1 can extend female longevity, but tissue-specific
      deletion may have varying effects on health span. The deletion of Nrip1 in WAT
      may delay senescence in WAT and extend health span.

PMID- 29346517
TI  - Does Telomere Length Indicate Biological, Physical, and Cognitive Health Among
      Older Adults? Evidence from the Health and Retirement Study.
AB  - Telomere length (TL) has been suggested as a biomarker that can indicate
      individual variability in the rate of aging. Yet, it remains unclear whether TL
      is related to recognized indicators of health in an aging, older nationally
      representative sample. We examine whether TL is associated with 15 biological,
      physical, and cognitive markers of health among older adults ages 54+. TL was
      assayed from saliva using quantitative polymerase chain reaction (T/S ratio) in
      the 2008 Health and Retirement Study (n = 4,074). We estimated probability of
      high-risk levels across indictors of health by TL and age-singly and jointly. TL
      was associated with seven indicators of poor functioning: high-density
      lipoprotein and total cholesterol, cystatin C, pulse pressure, body mass index,
      lung function, and walking speed. However, after adjusting for age, associations
      were substantially attenuated; only associations with cholesterol and lung
      function remained significant. Additionally, findings show TL did not add to the
      predictive power of chronological age in predicting poor functioning. While TL
      may not be a useful clinical marker of functional aging in an older adult
      population, it may still play an important role in longitudinal studies in young
      and middle aged populations that attempt to understand aging.

PMID- 29346518
TI  - Determinants of Health Trajectories in England and the United States: An Approach
      to Identify Different Patterns of Healthy Aging.
AB  - Background: Aging is a multidimensional process with a remarkable interindividual
      variability. This study is focused on identifying groups of population with
      similar aging patterns, and to define the health trajectories of these groups.
      Sociodemographic and health determinants of these trajectories are also
      identified. Methods: Data from the English Longitudinal Study of Aging (ELSA) and
      the Health and Retirement Study (HRS) were used. A set of self-reported health
      items and measured tests were used to generate a latent health metric by means of
      a Bayesian multilevel IRT model, assessing the ability of the metric to predict
      mortality. Then, a Growth Mixture Model (GMM) was conducted in each study to
      identify latent classes and assess health trajectories. Kaplan-Meier survival
      curves were obtained for each class and a multinomial logistic regression was
      used to identify determinants of these trajectories. Results: The health score
      generated showed an adequate ability to predict mortality over 10 years in ELSA
      (AUC = 0.74; 95% CI: 0.72, 0.75) and HRS (AUC = 0.74; 95% CI: 0.73, 0.75). By
      means of GMM, four latent classes were identified in ELSA and five in HRS.
      Chronic conditions, no qualification and low level of household wealth were
      associated to the classes which showed a higher mortality in both studies.
      Conclusion: The method based on the creation of a common metric of health and the
      use of GMM to identify similar patterns of aging, allows for the comparison of
      trajectories of health across longitudinal surveys. Multimorbidity, educational
      level, and household wealth could be considered as determinants associated to
      these trajectories.

PMID- 29346519
TI  - Final results of a multi-institutional phase II trial of reirradiation with
      concurrent weekly cisplatin and cetuximab for recurrent or second primary
      squamous cell carcinoma of the head and neck.
AB  - Background: The optimal regimen of chemotherapy and reirradiation (re-XRT) for
      recurrent head and neck squamous cell carcinoma (HNSCC) is controversial. We
      report the final outcomes of a multicenter phase II trial evaluating cetuximab
      and cisplatin-based chemotherapy concurrent with re-XRT for patients with
      recurrent HNSCC. Materials and methods: Patients with unresectable recurrent
      disease or positive margins after salvage surgery arising within a previously
      irradiated field with KPS >= 70 were eligible for this trial. Cetuximab 400 mg/m2
      was delivered as a loading dose in week 1 followed by weekly cetuximab 250 mg/m2
      and cisplatin 30 mg/m2 concurrent with 6 weeks of intensity-modulated
      radiotherapy to a dose of 60-66 Gy in 30 daily fractions. Patients who previously
      received both concurrent cetuximab and cisplatin with radiation or who received
      radiotherapy less than 6 months prior were ineligible. Results: From 2009 to
      2013, 48 patients enrolled on this trial, 2 did not receive any protocol
      treatment. Of the remaining 46 patients, 34 were male and 12 female, with a
      median age of 62 years (range 36-85). Treatment was feasible and only 1 patient
      did not complete the treatment course. Common grade 3 or higher acute toxicities
      were lymphopenia (46%), pain (22%), dysphagia (13%), radiation dermatitis (13%),
      mucositis (11%) and anorexia (11%). There were no grade 5 acute toxicities. Eight
      grade 3 late toxicities were observed, four of which were swallowing related.
      With a median follow-up of 1.38 years, the 1-year overall survival (OS) was 60.4%
      and 1-year recurrence-free survival was 34.1%. On univariate analysis, OS was
      significantly improved with young age (P = 0.01). OS was not associated with
      radiation dose, surgery before re-XRT or interval from prior XRT. Conclusions:
      Concurrent cisplatin and cetuximab with re-XRT is feasible and offers good
      treatment outcomes for patients with high-risk features. Younger patients had
      significantly improved OS. ClinicalTrials.Gov Identifier: NCT00833261.

PMID- 29346520
TI  - Uncovering the links between systemic hormones and oncogenic signaling in the
      pathogenesis of meningioma.

PMID- 29346522
TI  - Serious Fall Injury History and Adverse Health Outcomes After Initiating
      Hemodialysis Among Older U.S. Adults.
AB  - Background: Although older adults with predialysis chronic kidney disease are at
      higher risk for falls, the prognostic significance of a serious fall injury prior
      to dialysis initiation has not been well described in the end-stage renal disease
      population. Methods: We examined the association between a serious fall injury in
      the year prior to starting hemodialysis and adverse health outcomes in the year
      following dialysis initiation using a retrospective cohort study of U.S. Medicare
      beneficiaries >= 67 years old who initiated dialysis in 2010-2012. Serious fall
      injuries were defined using diagnostic codes for falls plus an injury (fracture,
      joint dislocation, or head injury). Health outcomes, defined as time-to-event
      variables within the first year of dialysis, included four outcomes: a subsequent
      serious fall injury, hospital admission, post-acute skilled nursing facility
      (SNF) utilization, and mortality. Results: Among this cohort of 81,653 initiating
      hemodialysis, 2,958 (3.6%) patients had a serious fall injury in the year prior
      to hemodialysis initiation. In the first year of dialysis, 7.6% had a subsequent
      serious fall injury, 67.6% a hospitalization, 30.7% a SNF claim, and 26.1% died.
      Those with versus without a serious fall injury in the year prior to hemodialysis
      initiation were at higher risk (hazard ratio, 95% confidence interval) for a
      subsequent serious fall injury (2.65, 2.41-2.91), hospitalization (1.11, 1.06
      1.16), SNF claim (1.40, 1.30-1.50), and death (1.14, 1.06-1.22). Conclusions: For
      older adults initiating dialysis, a history of a serious fall injury may provide
      prognostic information to support decision making and establish expectations for
      life after dialysis initiation.

PMID- 29346523
TI  - Association Between Timed Up and Go Test and Future Dementia Onset.
AB  - Background: This study evaluated whether baseline results of the Timed Up and Go
      (TUG) test is associated with future dementia occurrence. Methods: Using the
      Korean National Health Insurance Service-National Health Screening Cohort
      database, we identified 49,283 subjects without a dementia diagnosis who
      participated in the National Screening Program for Transitional Ages at 66 years
      of age during 2007-2012. Gait impairment was defined as taking longer than 10
      seconds to perform the TUG test. Dementia occurrence was defined by the first
      prescription for acetylcholinesterase inhibitors or N-Methyl-D-Aspartate receptor
      antagonist with an International Classification of Diseases 10th Revision (ICD
      10) code for dementia (F00, F01, F02, F03, G30, F051, or G311) during 2007-2013.
      Cox proportional hazard regression models were used to assess the hazard ratios
      for dementia occurrence according to baseline TUG test results. Results: Mean
      follow-up period was 3.8 years. Incidence rates of dementia were 4.6 and 6.8
      cases per 1,000 person-years in the normal and impaired TUG groups, respectively.
      The impaired TUG group showed a higher risk of total dementia incidence (adjusted
      hazard ratio [aHR], 1.34; 95% confidence interval [95% CI], 1.14-1.57). Subtype
      analysis showed that the impaired TUG group had a higher risk of Alzheimer's
      disease (aHR, 1.26; 95% CI, 1.06-1.51) and vascular dementia (aHR, 1.65; 95% CI,
      1.19-2.30). Conclusions: The TUG test result was associated with future dementia
      occurrence. More vigilant follow-up and early intervention to prevent dementia
      would benefit elderly people with impaired TUG test result.

PMID- 29346521
TI  - The intracellular and intercellular cross-talk during subsidiary cell formation
      in Zea mays: existing and novel components orchestrating cell polarization and
      asymmetric division.
AB  - Background: Formation of stomatal complexes in Poaceae is the outcome of three
      asymmetric and one symmetric cell division occurring in particular leaf
      protodermal cells. In this definite sequence of cell division events, the
      generation of subsidiary cells is of particular importance and constitutes an
      attractive model for studying local intercellular stimulation. In brief, an
      induction stimulus emitted by the guard cell mother cells (GMCs) triggers a
      series of polarization events in their laterally adjacent protodermal cells. This
      signal determines the fate of the latter cells, forcing them to divide
      asymmetrically and become committed to subsidiary cell mother cells (SMCs).
      Scope: This article summarizes old and recent structural and molecular data
      mostly derived from Zea mays, focusing on the interplay between GMCs and SMCs,
      and on the unique polarization sequence occurring in both cell types. Recent
      evidence suggests that auxin operates as an inducer of SMC
      polarization/asymmetric division. The intercellular auxin transport is
      facilitated by the distribution of a specific transmembrane auxin carrier and
      requires reactive oxygen species (ROS). Interestingly, the local differentiation
      of the common cell wall between SMCs and GMCs is one of the earliest features of
      SMC polarization. Leucine-rich repeat receptor-like kinases, Rho-like plant
      GTPases as well as the SCAR/WAVE regulatory complex also participate in the
      perception of the morphogenetic stimulus and have been implicated in certain
      polarization events in SMCs. Moreover, the transduction of the auxin signal and
      its function are assisted by phosphatidylinositol-3-kinase and the products of
      the catalytic activity of phospholipases C and D. Conclusion: In the present
      review, the possible role(s) of each of the components in SMC polarization and
      asymmetric division are discussed, and an overall perspective on the mechanisms
      beyond these phenomena is provided.

PMID- 29346524
TI  - Effects of a Primary Care-Based Multifactorial Intervention on Physical and
      Cognitive Function in Frail, Elderly Individuals: A Randomized Controlled Trial.
AB  - Background: Detecting and managing frailty at early stages can prevent disability
      and other adverse outcomes. The study aim was to evaluate whether a
      multifactorial intervention program could modify physical and cognitive frailty
      parameters in elderly individuals. Methods: We conducted a multicenter,
      randomized, single-blind, parallel-group trial in community-living prefrail/frail
      elderly individuals in Barcelona. A total of 352 patients, aged >=65 years old
      with positive frailty screening, was randomized into two groups to receive a 12
      week multidisciplinary intervention or usual care, with concealed allocation. The
      intervention consisted of: exercise training, intake of hyperproteic nutritional
      shakes, memory training, and medication review. Main outcome assessments with
      multivariate analysis were conducted at 3 and 18 months. Results: A total of 347
      participants (98.6%) completed the study, mean age 77.3 years, 89 prefrail
      subjects (25.3%), and 75.3% female (n = 265). Eighteen-month assessments were
      performed in 76% of the sample. After 3 and 18 months, adjusted means difference
      between-groups showed significant improvements for the intervention group in all
      comparisons: Short Physical Performance Battery score improved 1.58 and 1.36
      points (p < .001), handgrip strength 2.84 and 2.49 kg (p < .001), functional
      reach 4.3 and 4.52 cm (p < .001), and number of prescriptions decreased 1.39 and
      1.09 (p < .001), respectively. Neurocognitive battery also showed significant
      improvements across all dimensions at 3 and 18 months. Conclusions: A physical,
      nutritional, neurocognitive, and pharmacological multifaceted intervention was
      effective in reversing frailty measures both at short-term and 18 months. Lasting
      benefits of a multi-intervention program among frail elderly individuals
      encourage its prioritization.

PMID- 29346525
TI  - Frailty Syndrome and Genomic Instability in Older Adults: Suitability of the
      Cytome Micronucleus Assay As a Diagnostic Tool.
AB  - Frailty, a condition involving increased risk of disability and mortality in
      older adults, has emerged as a reliable way to predict the effect of aging.
      Genomic instability may help to anticipate recognition of frail individuals and
      improving frailty outcomes. Our objective was to evaluate the potential of the
      micronucleus frequency, evaluated in lymphocytes and buccal cells, to anticipate
      frailty identification and improve diagnosis reliability. Our results, from a
      group of older adults over 65, showed that frail individuals had significantly
      higher frequencies of micronucleus in lymphocytes (19.16 +/- 0.66 vs. 13.07 +/-
      0.78, p < .001) and of binucleated buccal cells (82.65 +/- 3.42 vs. 37.16 +/-
      2.85, p < .001) and lower frequencies of pyknotic and condensed chromatin buccal
      cells, than nonfrail subjects. When cognitive status was considered, similar
      results were obtained. Moreover, the presence of frailty and cognitive impairment
      were independently related to increases in frequencies of lymphocyte micronucleus
      and binucleated buccal cells. Our results encourage the use of micronucleus
      frequency in lymphocytes as a complement to clinical parameters in frailty
      identification. However, these results have to be further evaluated in prefrail
      patients, to better understand the connection between genomic instability and
      frailty and to establish these parameters as actual biomarkers of frailty in
      clinical practice.

PMID- 29346526
TI  - What Is the Impact of Physical Activity and Physical Function on the Development
      of Multimorbidity in Older Adults Over Time? A Population-Based Cohort Study.
AB  - Background: Multimorbidity is recognized internationally as having a serious
      impact on health outcomes. It is associated with reduced quality of life,
      increased health care utilization, and future functional decline. Physical
      activity is associated with good health and psychological well-being. The aim of
      this study was to identify the impact of physical activity and physical function
      on the development and worsening of multimorbidity over time. Methods: Using The
      Irish Longitudinal Study on Ageing (TILDA), we analyzed 4,823 participants >=50
      years with and without multimorbidity. Multimorbidity was defined as the presence
      of >=2 chronic conditions. Development of multimorbidity was measured as the
      accrual of additional conditions over a 2-year period. Physical activity and
      physical function were measured using the International Physical Activity
      Questionnaire (IPAQ), gait speed (m/sec), and grip strength (kg). Results:
      Sixteen groups of chronic conditions were included in analyses. 53.7% of included
      participants had multimorbidity at baseline and 71.7% at follow-up. Six hundred
      and thirty-eight of 2,092 (30.4%) participants without multimorbidity and 1,005
      of 2,415 (41.6%) with existing multimorbidity developed new condition/s. Gait
      speed (relative risk [RR] = 0.67, confidence interval [CI]: 0.49-0.90), grip
      strength (RR = 0.98, CI: 0.97-0.99), and age (compared to 50-59 years, 60-69: RR
      = 1.30, CI: 1.11-1.52; >=70: RR = 1.35, CI: 1.03-1.77) were significantly
      associated with the development of multimorbidity and accrual of additional
      conditions. Conclusion: These results show that physical function is associated
      with the development and worsening of multimorbidity over time. They support the
      recent National Institute for Health & Care Excellence (NICE) Guidance on
      multimorbidity that suggests that patients with multimorbidity and reduced gait
      speed should be identified and targeted for interventions to improve health
      outcomes.

PMID- 29346527
TI  - Progesterone effects on extracellular vesicles in the sheep uterus.
AB  - Progesterone (P4) acts via the endometrium to promote conceptus growth and
      implantation for pregnancy establishment. Many cells release extracellular
      vesicles (EVs) that are membrane-bound vesicles of endosomal and plasma membrane
      origin. In sheep, endometrial-derived EVs were found to traffic to the conceptus
      trophectoderm. Thus, EVs are hypothesized to be an important mode of
      intercellular communication by transferring select RNAs, proteins, and lipids
      between the endometrium and conceptus. Electron microscopy analysis found that
      the endometrial luminal and glandular epithelia were the primary source of EVs in
      the uterus of cyclic sheep. Size exclusion chromatography and nanoparticle
      tracking analysis (NTA) found that total EV number in the uterine lumen increased
      from day 10 to 14 in cyclic sheep. Next, ewes were ovariectomized and hormone
      replaced to determine effects of P4 on the endometrium and EVs in the uterine
      lumen. Transcriptome analyses found that P4 regulated 1611 genes and nine miRNAs
      in the endometrium. Total EV number in the uterine lumen was increased by P4
      treatment. Small RNA sequencing of EVs detected expression of 768 miRNAs and
      determined that P4 regulated seven of those miRNAs. These studies provide
      fundamental new information on how P4 influences endometrial function to regulate
      conceptus growth for pregnancy establishment in sheep.

PMID- 29346528
TI  - A novel stromal lncRNA signature reprograms fibroblasts to promote the growth of
      oral squamous cell carcinoma via LncRNA-CAF/interleukin-33.
AB  - Stromal carcinoma-related fibroblasts (CAFs) are the main type of non-immune
      cells in the tumor microenvironment (TME). CAFs interact with cancer cells to
      promote tumor proliferation. Long non-coding RNAs (lncRNAs) are known to regulate
      cell growth, apoptosis and metastasis of cancer cells, but their role in stromal
      cells is unclear. Using RNA sequencing, we identified a stromal lncRNA signature
      during the transformation of CAFs from normal fibroblasts (NFs) in oral squamous
      cell carcinoma (OSCC). We uncovered an uncharacterized lncRNA, FLJ22447, which
      was remarkably up-regulated in CAFs, referred to LncRNA-CAF (Lnc-CAF) hereafter.
      Interleukin-33 (IL-33) was mainly located in the stroma and positively co
      expressed with Lnc-CAF to elevate the expression of CAF markers (alpha-SMA,
      vimentin and N-cadherin) in fibroblasts. In a co-culture system, IL-33 knockdown
      impaired Lnc-CAF-mediated stromal fibroblast activation, leading to decreased
      proliferation of tumor cells. Mechanistically, Lnc-CAF up-regulated IL-33 levels
      and prevented p62-dependent autophagy-lysosome degradation of IL-33, which was
      independent of LncRNA-protein scaffold effects. Treatment with the autophagy
      inducer, rapamycin, impaired the proliferative effect of Lnc-CAF/IL-33 by
      promoting IL-33 degradation. In turn, tumor cells further increased Lnc-CAF
      levels in stromal fibroblasts via exosomal Lnc-CAF. In patients with OSCC, high
      Lnc-CAF/IL-33 expression correlated with high TNM stage (n = 140). Moreover, high
      Lnc-CAF expression predicted poor prognosis. In vivo, Lnc-CAF knockdown
      restricted tumor growth and was associated with decreased Ki-67 expression and
      alpha-SMA+ CAF in the stroma. In conclusion, we identified a stromal lncRNA
      signature, which reprograms NFs to CAFs via Lnc-CAF/IL-33 and promotes OSCC
      development.

PMID- 29346529
TI  - Echocardiographic criteria to detect unicuspid aortic valve morphology.
AB  - Aims: Unicuspid aortic valve (UAV) is a rare congenital malformation associated
      with severe aortic stenosis or regurgitation. This study aimed to systematically
      determine echocardiographic criteria to identify UAV. Methods and results: All
      patients underwent a preoperative baseline examination, including
      echocardiography. A total of 69 patients with intraoperatively confirmed UAV
      underwent an aortic valve repair procedure between August 2001 and May 2011. To
      compare the findings of UAV cases with those of other valve morphologies, we
      examined 99 consecutive patients with a bicuspid aortic valve (BAV) and 103
      consecutive patients with a tricuspid aortic valve (TAV) undergoing isolated
      aortic valve surgery before May 2016. The mean age of the 271 patients was 44.2
      +/- 12.8 years; 85% were male, with a mean body mass index of 26.2 +/- 4.0 kg/m2.
      Patients with UAV were younger and had fewer co-morbidities than patients with
      BAV or TAV, respectively. The major criteria for the echocardiographic diagnosis
      of UAV were defined based on our preoperative examination as follows: (i) single
      commissural attachment zone, (ii) rounded, leaflet-free edge on the opposite side
      of the commissural attachment zone, (iii) eccentric valvular orifice during
      systole, and (iv) patient age <20 years and mean transvalvular gradient >15 mmHg.
      The minor criteria were defined as an associated thoracic aortopathy and age <40
      years. Three out of the four major criteria or two out of the four major criteria
      and one minor criterion were met in all patients with UAV and in none of the
      patients with BAV or TAV. Associated 95% confidence intervals were calculated for
      each estimate of sensitivity (94.7-100%) and specificity (98.1-100%), indicating
      that an adequate number of patients were included in each of the three groups.
      Conclusion: The proposed echocardiographic score appears to be a specific and
      sensitive method to distinguish UAV from BAV and TAV.

PMID- 29346530
TI  - Bacterioplankton composition in tropical high-elevation lakes of the Andean
      plateau.
AB  - High-elevation lakes in the tropics are subject to extreme environmental
      fluctuations and microbes may harbor a unique genomic repertoire, but their
      composition and diversity are largely unknown. Here, we compared the planktonic
      bacterial community composition (BCC) and diversity of three tropical lakes
      located in the high Andean plateau (>=4400 m above sea level) during the dry and
      wet season. Diversity in these lakes was higher in the cool and wet season than
      in the warm and dry one. Operational taxonomic units (OTUs) composition was
      significantly different among lakes and between seasons. Members of the class
      Opitutae, Spartobacteria, Burkholderiales and Actinobacteria were dominant, but
      only the hgcI clade (Actinobacteria) and the Comamonadaceae family
      (Burkholderiales) were shared between seasons among the three lakes. In general,
      a large percentage (up to 42%) of the rare OTUs was unclassified even at the
      family level. In one lake, a pycnocline and an anoxic water layer with high
      abundance of Thiocapsa sp. was found in the wet season indicating that the known
      polymictic thermal condition is not always given. Our study highlights the
      particular BCC of tropical high-elevation lakes and also how little is known
      about the variability in physico-chemical conditions of these ecosystems.

PMID- 29346531
TI  - Doppler assessment of aortic stenosis: a 25-operator study demonstrating why
      reading the peak velocity is superior to velocity time integral.
AB  - Aims: Measurements with superior reproducibility are useful clinically and
      research purposes. Previous reproducibility studies of Doppler assessment of
      aortic stenosis (AS) have compared only a pair of observers and have not explored
      the mechanism by which disagreement between operators occurs. Using custom
      designed software which stored operators' traces, we investigated the
      reproducibility of peak and velocity time integral (VTI) measurements across a
      much larger group of operators and explored the mechanisms by which disagreement
      arose. Methods and results: Twenty-five observers reviewed continuous wave (CW)
      aortic valve (AV) and pulsed wave (PW) left ventricular outflow tract (LVOT)
      Doppler traces from 20 sequential cases of AS in random order. Each operator
      unknowingly measured each peak velocity and VTI twice. VTI tracings were stored
      for comparison. Measuring the peak is much more reproducible than VTI for both PW
      (coefficient of variation 10.1 vs. 18.0%; P < 0.001) and CW traces (coefficient
      of variation 4.0 vs. 10.2%; P < 0.001). VTI is inferior because the steep early
      and late parts of the envelope are difficult to trace reproducibly. Dimensionless
      index improves reproducibility because operators tended to consistently over-read
      or under-read on LVOT and AV traces from the same patient (coefficient of
      variation 9.3 vs. 17.1%; P < 0.001). Conclusion: It is far more reproducible to
      measure the peak of a Doppler trace than the VTI, a strategy that reduces
      measurement variance by approximately six-fold. Peak measurements are superior to
      VTI because tracing the steep slopes in the early and late part of the VTI
      envelope is difficult to achieve reproducibly.

PMID- 29346532
TI  - What color should glacier algae be? An ecological role for red carbon in the
      cryosphere.
AB  - Red-colored secondary pigments in glacier algae play an adaptive role in melting
      snow and ice. We advance this hypothesis using a model of color-based absorption
      of irradiance, an experiment with colored particles in snow, and the natural
      history of glacier algae. Carotenoids and phenols-astaxanthin in snow-algae and
      purpurogallin in ice-algae-shield photosynthetic apparatus by absorbing
      overabundant visible wavelengths, then dissipating the excess radiant energy as
      heat. This heat melts proximal ice crystals, providing liquid-water in a 0
      degrees C environment and freeing up nutrients bound in frozen water. We show
      that purple-colored particles transfer 87%-89% of solar energy absorbed by black
      particles. However, red-colored particles transfer nearly as much (85%-87%) by
      absorbing peak solar wavelengths and reflecting the visible wavelengths most
      absorbed by nearby ice and snow crystals; this latter process may reduce
      potential cellular overheating when snow insulates cells. Blue and green
      particles transfer only 80%-82% of black particle absorption. In the experiment,
      red-colored particles melted 87% as much snow as black particles, while blue
      particles melted 77%. Green-colored snow-algae naturally occupy saturated snow
      where water is non-limiting; red-colored snow-algae occupy drier, water-limited
      snow. In addition to increasing melt, we suggest that esterified astaxanthin in
      snow-alga cells increases hydrophobicity to remain surficial.

PMID- 29346533
TI  - Density of Emerald Ash Borer (Coleoptera: Buprestidae) Adults and Larvae at Three
      Stages of the Invasion Wave.
AB  - Emerald ash borer (EAB) (Agrilus planipennis Fairmaire) (Coleoptera:
      Buprestidae), an invasive phloem-feeding buprestid, has killed hundreds of
      millions of ash (Fraxinus spp.) trees in the United States and two Canadian
      provinces. We evaluated EAB persistence in post-invasion sites and compared EAB
      adult captures and larval densities in 24 forested sites across an east-west
      gradient in southern Michigan representing the Core (post-invasion), Crest (high
      EAB populations), and Cusp (recently infested areas) of the EAB invasion wave.
      Condition of green ash (Fraxinus pennsylvanica Marsh) trees were recorded in
      fixed radius plots and linear transects in each site. Ash mortality was highest
      in Core sites in the southeast, moderate in Crest sites in central southern
      Michigan, and low in Cusp sites in the southwest. Traps and trap trees in Crest
      sites accounted for 75 and 60% of all EAB beetles captured in 2010 and 2011,
      respectively. Populations of EAB were present in all Core sites and traps in
      these sites captured 13% of all beetles each year. Beetle captures and larval
      densities at Cusp sites roughly doubled between 2010 and 2011, reflecting the
      increasing EAB populations. Sticky bands on girdled trees captured the highest
      density of EAB beetles per m2 of area, while baited double-decker traps had the
      highest detection rates and captured the most beetles. Larval densities were
      higher on girdled ash than on similar ungirdled trees and small planted trees.
      Woodpecker predation and a native larval parasitoid were present in all three
      invasion regions but had minor effects on ash survival and EAB densities.

PMID- 29346534
TI  - Microbial community structure of sea spray aerosols at three California beaches.
AB  - We characterized the microbial communities in sea spray aerosols (SSA), water and
      sand of three beaches in central California (Cowell Beach, Baker Beach and Lovers
      Point) by sequencing the V4 region of the 16S rRNA gene. Average concentrations
      of 16S rRNA genes in SSA ranged from 2.4 * 104 to 1.4 * 105 gene copies per m3 of
      air. A total of 9781 distinct OTUs were identified in SSA and of these, 1042 OTUs
      were found in SSA of all beaches. SSA microbial communities included marine taxa,
      as well as some associated with the terrestrial environment. SSA taxa included
      organisms that play important roles in biogeochemical cycling of elements such as
      Planctomyces and Synechococcus, as well as those representing potential pathogens
      and fecal indicator bacteria including Staphylococcus epidermidis and
      Enterococcus spp. There were a large number of shared OTUs among SSA and water,
      and there was relatively high similarity between SSA and water communities.
      Results are consistent with a conceptual model where SSA is generated by breaking
      waves and bubble bursting in marine waters and that enables the transport of
      microorganisms from the sea to sand or other environments.

PMID- 29346535
TI  - Tricuspid regurgitation in acute heart failure: is there any incremental risk?
AB  - Aim: Significant tricuspid regurgitation (TR) is common in heart failure (HF) and
      portends poor prognosis. We sought to determine whether the poor outcome results
      from the TR itself, or whether the TR is a surrogate marker of advanced left
      sided myocardial or valvular heart disease. Methods and results: We studied 639
      patients admitted for acute HF. The relationship between TR severity and the
      endpoint of readmission for HF or mortality was assessed after adjustment for
      multiple clinical and echocardiographic parameters. Higher TR grade was
      associated with higher congestion score and with other cardiac abnormalities
      including reduced left ventricular systolic function, moderate or severe mitral
      regurgitation, pulmonary hypertension (PH, defined as pulmonary artery systolic
      pressure >= 50 mmHg), and right ventricular dysfunction (all P < 0.001). Only 7%
      of patients with moderate or severe TR were free of other cardiac lesions. In
      adjusted models, moderate or severe TR was not associated with readmission for HF
      or mortality [hazard ratio (HR) 1.24, 95% confidence interval (95% CI) 0.97
      1.57]. Patients with moderate/severe TR had similar risk for HF readmission or
      death compared with patients with trivial/mild TR when PH was not present (HR
      1.17; 95% CI 0.78-1.75, P = 0.40) whereas the risk was higher in moderate/severe
      TR and PH (HR 1.78; 95% CI 1.34-2.36, P < 0.0001). Conclusion: Patients
      presenting with symptomatic HF and significant TR have multiple coexisting
      cardiac abnormalities. TR provides no additive risk in the presence of normal or
      mildly elevated pulmonary pressures. However, it is associated with excess
      rehospitalizations and mortality in patients with PH.

PMID- 29346536
TI  - Residual carcinoma cells after chemoradiotherapy for esophageal squamous cell
      carcinoma patients: striving toward appropriate judgment of biopsy.
AB  - In esophageal squamous cell carcinoma (ESCC) patients who are treated with
      chemoradiotherapy (CRT), identification of the presence or absence of residual or
      recurrent carcinoma is usually pivotal in their clinical management. In addition,
      the extent of carcinoma invasion into the esophageal wall could determine the
      clinical outcome of these patients following CRT. Therefore, in this study, we
      evaluated the response to CRT both macroscopically and histologically in a
      consecutive series of 42 ESCC patients receiving neoadjuvant chemoradiotherapy
      following curative esophageal resection at Tohoku University Hospital between
      August 2011 and December 2012. The histological grading of tumor regression was
      as follows: grade 3, markedly effective (no viable residual tumor cells); grade
      2, moderately effective (residual tumor cells in less than one-third of the
      tumor); grade 1, slightly effective (1b, residual tumor cells in one-third to two
      thirds of the tumor; 1a, residual tumor cells in more than two-thirds of the
      tumor); and grade 0, ineffective. In this study, we selected grade 2 and 1b cases
      because they might show a complete response with definitive CRT. We evaluated the
      presence of any residual in situ lesions and tumor depth in detail. The grading
      of tumor regression in primary sites was as follows: grade 3 (7 cases), grade 2
      (16 cases), grade 1b (13 cases), and grade 1a (6 cases). The concordance rate
      between macroscopic and histopathological evaluation on the depth of the tumor
      was 40% (17/42). Among 29 cases (grade 2 and grade 1b), intraepithelial lesions
      were not detected in 17 cases, and tumor nests were not detected in the lamina
      propria mucosae in 9 cases. The results of this study highlight the difficulties
      of detecting residual carcinoma cells using conventional endoscopic biopsy in
      patients who have received CRT. Therefore, when residual cancer is clinically
      suspected in patients who have received CRT, the biopsy specimen should be
      obtained from the deep layer of the esophagus whenever possible. Additionally,
      close follow-up is required using positron emission tomography/computed
      tomography, endoscopy, and other radiological evaluations.

PMID- 29346537
TI  - Cerebral mitochondrial dysfunction associated with deep hypothermic circulatory
      arrest in neonatal swine.
AB  - OBJECTIVES: Controversy remains regarding the use of deep hypothermic circulatory
      arrest (DHCA) in neonatal cardiac surgery. Alterations in cerebral mitochondrial
      bioenergetics are thought to contribute to ischaemia-reperfusion injury in DHCA.
      The purpose of this study was to compare cerebral mitochondrial bioenergetics for
      DHCA with deep hypothermic continuous perfusion using a neonatal swine model.
      METHODS: Twenty-four piglets (mean weight 3.8 kg) were placed on cardiopulmonary
      bypass (CPB): 10 underwent 40-min DHCA, following cooling to 18 degrees C, 10
      underwent 40 min DHCA and 10 remained at deep hypothermia for 40 min; animals
      were subsequently rewarmed to normothermia. 4 remained on normothermic CPB
      throughout. Fresh brain tissue was harvested while on CPB and assessed for
      mitochondrial respiration and reactive oxygen species generation. Cerebral
      microdialysis samples were collected throughout the analysis. RESULTS: DHCA
      animals had significantly decreased mitochondrial complex I respiration, maximal
      oxidative phosphorylation, respiratory control ratio and significantly increased
      mitochondrial reactive oxygen species (P < 0.05 for all). DHCA animals also had
      significantly increased cerebral microdialysis indicators of cerebral ischaemia
      (lactate/pyruvate ratio) and neuronal death (glycerol) during and after
      rewarming. CONCLUSIONS: DHCA is associated with disruption of mitochondrial
      bioenergetics compared with deep hypothermic continuous perfusion. Preserving
      mitochondrial health may mitigate brain injury in cardiac surgical patients.
      Further studies are needed to better understand the mechanisms of neurological
      injury in neonatal cardiac surgery and correlate mitochondrial dysfunction with
      neurological outcomes.

PMID- 29346538
TI  - Vitamin K5 is an efficient photosensitizer for ultraviolet A light inactivation
      of bacteria.
AB  - Photodynamic treatment combining light and a photosensitizer molecule can be an
      effective method to inactivate pathogenic bacteria. This study identified vitamin
      K5 as an efficient photosensitizer for ultraviolet light A (UVA)-induced
      bacterial inactivation. Six bacterial species, Bacillus cereus (vegetative form),
      Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus
      epidermidis, Klebsiella pneumoniae, and two species of antibiotic-resistant
      bacteria, Pseudomonas aeruginosa* and Staphylococcus aureus*, were suspended in
      aqueous solutions with or without vitamin K5 and exposed to UVA irradiation. UVA
      irradiation (5.8 J cm-2) with vitamin K5 (1600 MUmol l-1) reduced the colony
      forming units (CFU) of these bacteria by three to seven logs. Antibiotic
      resistant bacteria were also susceptible to the bactericidal effects of UVA and
      vitamin K5 combination treatment. Inactivation of bacteria in human plasma
      required higher doses of UVA light and vitamin K5. UVA irradiation (30 J cm-2)
      with vitamin K5 (2000 MUmol l-1) reduced E. coli and S. aureus spiked into human
      plasma by seven logs CFU/ml. Reactive oxygen species, such as superoxide anion
      radicals and hydroxyl radicals, were found to be generated in vitamin K5 aqueous
      solution after UVA irradiation, suggesting these oxygen species may mediate the
      inactivation of the bacteria.

PMID- 29346539
TI  - CORRIGENDUM FOR "Functional Characterization of MicroRNA-27a-3p Expression in
      Human Polycystic Ovary Syndrome".

PMID- 29346540
TI  - Blood and lymphatic vessels contribute to the impact of the immune
      microenvironment on clinical outcome in non-small-cell lung cancer.
AB  - OBJECTIVES: Lymphangiogenesis plays a critical role in the immune response,
      tumour progression and therapy effectiveness. The aim of this study was to
      determine whether the interplay between the lymphatic and the blood
      microvasculature, tumour-infiltrating lymphocytes and the programmed death 1 (PD
      1)/programmed death ligand 1 (PD-L1) immune checkpoint constitutes an immune
      microenvironment affecting the clinical outcome of patients with non-small-cell
      lung cancer. METHODS: Samples from 50 squamous cell carcinomas and 42
      adenocarcinomas were subjected to immunofluorescence to detect blood and
      lymphatic vessels. CD3pos, CD8pos and PD-1pos tumour-infiltrating lymphocytes and
      tumour PD-L1 expression were assessed by immunohistochemical analysis. RESULTS:
      Quantification of vascular structures documented a peak of lymphatics at the
      invasive margin together with a decreasing gradient of blood and lymphatic
      vessels from the peritumour area throughout the neoplastic core. Nodal
      involvement and pathological stage were strongly associated with vascularization,
      and an increased density of vessels was detected in samples with a higher
      incidence of tumour-infiltrating lymphocytes and a lower expression of PD-L1.
      Patients with a high PD-L1 to PD-1 ratio and vascular rarefaction had a gain of
      10 months in overall survival compared to those with a low ratio and prominent
      vascularity. CONCLUSIONS: Microvessels are an essential component of the cancer
      immune microenvironment. The clinical impact of the PD-1/PD-L1-based immune
      contexture may be implemented by the assessment of microvascular density to
      potentially identify patients with non-small-cell lung cancer who could benefit
      from immunotherapy and antiangiogenic treatment.

PMID- 29346541
TI  - Practical implications of erythromycin resistance gene diversity on surveillance
      and monitoring of resistance.
AB  - Use of antibiotics in human and animal medicine has applied selective pressure
      for the global dissemination of antibiotic-resistant bacteria. Therefore, it is
      of interest to develop strategies to mitigate the continued amplification and
      transmission of resistance genes in environmental reservoirs such as farms,
      hospitals and watersheds. However, the efficacy of mitigation strategies is
      difficult to evaluate because it is unclear which resistance genes are important
      to monitor, and which primers to use to detect those genes. Here, we evaluated
      the diversity of one type of macrolide antibiotic resistance gene (erm) in one
      type of environment (manure) to determine which primers would be most informative
      to use in a mitigation study of that environment. We analyzed all known erm genes
      and assessed the ability of previously published erm primers to detect the
      diversity. The results showed that all known erm resistance genes group into 66
      clusters, and 25 of these clusters (40%) can be targeted with primers found in
      the literature. These primers can target 74%-85% of the erm gene diversity in the
      manures analyzed.

PMID- 29346542
TI  - Hepatitis B in Moroccan-Dutch: a qualitative study into determinants of screening
      participation.
AB  - Background: Chronic hepatitis B (HBV) leads to an increased risk for liver
      cirrhosis and liver cancer. In the Netherlands, chronic HBV prevalence in the
      general population is 0.20%, but 3.77% in first generation immigrants. Our aim
      was to identify determinants associated with the intention to participate in HBV
      testing among first generation Moroccan immigrants, one of the two largest
      immigrant groups targeted for screening. Methods: Semi-structured interviews were
      held with first (n = 9) and second generation (n = 10) Moroccan-Dutch immigrants,
      since second generation immigrants frequently act as their parents' brokers in
      healthcare. Results: Most participants had little knowledge about hepatitis B,
      but had a positive attitude towards screening. Facilitators for screening
      intention were perceived susceptibility to and severity of disease, positive
      attitude regarding prevention, wishing to know their hepatitis B status and to
      prevent potential hepatitis B transmission to others. Additional cultural
      facilitators included fear (of developing cancer), and existing high health care
      utilization; a religious facilitator was the responsibility for one's own health
      and that of others. Barriers included lack of awareness and knowledge, practical
      issues, not having symptoms, negative attitude regarding prevention, fear about
      the test result and low-risk perception. A cultural barrier was shame and stigma,
      and a religious barrier was fatalism. Conclusion: We identified important
      facilitators and barriers, which we found, can be interpreted differently.
      Specific and accurate information should be provided, accompanied by strategies
      to address shame and stigma, in which Islamic religious leaders could play a role
      in bringing information across.

PMID- 29346543
TI  - The Impact of Reported Beta-Lactam Allergy in Hospitalized Patients With
      Hematologic Malignancies Requiring Antibiotics.
AB  - Background: Patients hospitalized with hematologic malignancy are particularly
      vulnerable to infection. The impact of reported beta-lactam (BL) allergy in this
      population remains unknown. Methods: This was a retrospective cohort study of
      adult inpatients with hematologic malignancy admitted at 2 tertiary care
      hospitals from 2010 through 2015. The primary outcome was hospital length of stay
      (LOS) after administration of the first antibiotic. Secondary outcomes included
      readmission, mortality, complications, hospital charges, and antibiotic usage.
      Our goal was to define the impact of BL-only allergy (BLOA) label on clinical
      outcomes compared to those with no BL allergy (NBLA) in hematologic malignancy
      inpatients who required systemic antibiotics. Results: In our cohort (n = 4671),
      38.3% had leukemia, 4.9% had Hodgkin lymphoma, 36.1% had non-Hodgkin lymphoma,
      and 20.7% had multiple myeloma. Among patients, 35.1% reported antibiotic
      allergy, and 14.1% (n = 660) had BLOA (including 9.3% with penicillin-only
      allergy and 3.3% cephalosporin-only allergy). Patients with BLOA had longer
      median LOS compared to patients with NBLA (11.3 vs 7.6 days, P < .001), which
      remained significant after multivariable adjustment. Patients with BLOA also had
      significantly worse outcomes in terms of mortality rate at 30 days (7.6% vs 5.3%,
      P = .017) and 180 days (15.8% vs 12.2%, P = .013), 30-day readmission rate,
      Clostridium difficile rate, hospital charges ($223 046 vs $173 256, P < .001),
      antibiotic classes used, and antibiotic duration. Conclusions: In hospitalized
      patients with hematologic malignancy, patients with reported BL allergy had worse
      clinical outcomes and higher healthcare cost than those without BL allergy label.

PMID- 29346544
TI  - So low... so far so good: neurocognitive impact of lowering LDL-C levels with
      PCSK9 inhibitors.

PMID- 29346546
TI  - Identifying cardiac pathologies with coronary wave intensity analysis: an
      enrichment to the ever-expanding coronary haemodynamics armamentarium?

PMID- 29346545
TI  - Influence of Nicotine Metabolism Ratio on [11C]-(+)-PHNO PET Binding in Tobacco
      Smokers.
AB  - Background: Identifying the biological basis of smoking cessation success is of
      growing interest. The rate of nicotine metabolism, measured by the nicotine
      metabolite ratio, affects multiple aspects of nicotine dependence. Fast nicotine
      metabolizers tend to smoke more, experience more withdrawal and craving, and have
      lower cessation rates compared with slow metabolizers. The nicotine metabolite
      ratio predicts treatment response, and differences in brain activation between
      fast metabolizers and slow metabolizers have been reported in fMRI studies. As
      reinforcing/rewarding effects of tobacco are associated with dopamine
      transmission, the purpose of the present study was to study the dopaminergic
      system in human smokers based on their nicotine metabolite ratio. Methods: The
      first aim of the study was to explore if there were differences in D2 and D3
      receptor binding between fast metabolizers and slow metabolizers during
      abstinence. The second aim was to explore smoking-induced dopamine release in
      both groups. Participants underwent 2 [11C]-(+)-PHNO PET scans: one scan during
      abstinence and the other after smoking a tobacco cigarette. Subjective measures
      were recorded and blood was drawn for measurement of nicotine and cotinine
      levels. Results: During abstinence, slow metabolizers (n = 13) had lower [11C]
      (+)-PHNO binding potential than fast metabolizers (n = 15) restricted to the D2
      regions of the associative striatum and sensorimotor striatum. After smoking a
      cigarette, [11C]-(+)-PHNO binding potential was decreased in the limbic striatum
      and ventral pallidum, suggestive of increases in dopamine, but there were no
      nicotine metabolite ratio differences. Conclusions: Further studies are required
      to delineate if differences in [11C]-(+)-PHNO binding between slow metabolizers
      and fast metabolizers at abstinence baseline are preexisting traits or induced by
      prolonged tobacco use.

PMID- 29346548
TI  - Impact of the EURO-2016 football cup on emergency department visits related to
      alcohol and injury.
AB  - In Marseille, the 2016 EURO football cup days were independently associated with
      a 43% increase in alcohol-related visits in the Emergency Department (ED).
      Patients admitted for alcohol consumption were younger (41 vs. 46.6; P < 0.001),
      more often male (82.8% vs. 60.1%; P < 0.001) and more often admitted as
      inpatients (24.0% vs. 16.5%; P = 0.03) than those admitted for injury. Unlike
      reported in previous studies, injury-related visits did not increase. This could
      be explained by coding practice variability between EDs (alcohol or injury). To
      account for this variability, both diagnosis groups must be separately included
      when using ED data for preparing and monitoring major gatherings.

PMID- 29346547
TI  - How to do (or not to do) ... a health financing incidence analysis.
AB  - Financing incidence analysis (FIA) assesses how the burden of health financing is
      distributed in relation to household ability to pay (ATP). In a progressive
      financing system, poorer households contribute a smaller proportion of their ATP
      to finance health services compared to richer households. A system is regressive
      when the poor contribute proportionately more. Equitable health financing is
      often associated with progressivity. To conduct a comprehensive FIA, detailed
      household survey data containing reliable information on both a cardinal measure
      of household ATP and variables for extracting contributions to health services
      via taxes, health insurance and out-of-pocket (OOP) payments are required.
      Further, data on health financing mix are needed to assess overall FIA. Two major
      approaches to conducting FIA described in this article include the structural
      progressivity approach that assesses how the share of ATP (e.g. income) spent on
      health services varies by quantiles, and the effective progressivity approach
      that uses indices of progressivity such as the Kakwani index. This article
      provides some detailed practical steps for analysts to conduct FIA. This includes
      the data requirements, data sources, how to extract or estimate health payments
      from survey data and the methods for assessing FIA. It also discusses data
      deficiencies that are common in many low- and middle-income countries (LMICs).
      The results of FIA are useful in designing policies to achieve an equitable
      health system.

PMID- 29346550
TI  - Coronary microvascular dysfunction and heart failure with preserved ejection
      fraction as female-pattern cardiovascular disease: the chicken or the egg?

PMID- 29346549
TI  - Transcriptome and functional analysis in a Drosophila model of NGLY1 deficiency
      provides insight into therapeutic approaches.
AB  - Autosomal recessive loss-of-function mutations in N-glycanase 1 (NGLY1) cause
      NGLY1 deficiency, the only known human disease of deglycosylation. Patients
      present with developmental delay, movement disorder, seizures, liver dysfunction
      and alacrima. NGLY1 is a conserved cytoplasmic component of the Endoplasmic
      Reticulum Associated Degradation (ERAD) pathway. ERAD clears misfolded proteins
      from the ER lumen. However, it is unclear how loss of NGLY1 function impacts ERAD
      and other cellular processes and results in the constellation of problems
      associated with NGLY1 deficiency. To understand how loss of NGLY1 contributes to
      disease, we developed a Drosophila model of NGLY1 deficiency. Loss of NGLY1
      function resulted in developmental delay and lethality. We used RNAseq to
      determine which processes are misregulated in the absence of NGLY1. Transcriptome
      analysis showed no evidence of ER stress upon NGLY1 knockdown. However, loss of
      NGLY1 resulted in a strong signature of NRF1 dysfunction among downregulated
      genes, as evidenced by an enrichment of genes encoding proteasome components and
      proteins involved in oxidation-reduction. A number of transcriptome changes also
      suggested potential therapeutic interventions, including dysregulation of GlcNAc
      synthesis and upregulation of the heat shock response. We show that increasing
      the function of both pathways rescues lethality. Together, transcriptome analysis
      in a Drosophila model of NGLY1 deficiency provides insight into potential
      therapeutic approaches.

PMID- 29346551
TI  - Brazil's Family Health Strategy: factors associated with programme uptake and
      coverage expansion over 15 years (1998-2012).
AB  - Universal Health Coverage (UHC) is one of the United Nations Sustainable
      Development Goals (SDGs). Achieving UHC will require strong health systems to
      promote and deliver equitable and integrated healthcare services through primary
      healthcare (PHC). In Brazil, the Family Health Strategy (FHS) delivers PHC
      through the public health system. Created in 1994, the FHS covered almost 123
      million individuals (63% of the Brazilian population) by 2015. The FHS has been
      associated with many health improvements, but gaps in coverage still remain. This
      article examines factors associated with the implementation and expansion of the
      FHS across 5419 Brazilian municipalities from 1998 to 2012. The proportion of the
      municipal population covered by the FHS over time was assessed using a
      longitudinal multilevel model for change that accounted for variables covering
      eight domains: economic development, healthcare supply, healthcare needs/access,
      availability of other sources of healthcare, political context, geographical
      isolation, regional characteristics and population size. Data were obtained from
      multiple publicly available sources. During the 15-year study period, national
      coverage of the FHS increased from 4.4% to 54%, with 58% of the municipalities
      having population coverage of 95% or more, and municipalities that had not
      adopted the programme decreased from 86.4% to 4.9%. The increase in FHS uptake
      and coverage was not homogenous across municipalities, and was positively
      associated with small population size, low population density, low coverage of
      private health insurance, low level of economic development, alignment of the
      political party of the Mayor and the state Governor, and availability of
      healthcare supply. Efforts to expand the FHS coverage will need to focus on
      increasing the availability of health personnel, devising financial incentives
      for municipalities to uptake/expand the FHS and devising new policies that
      encompass both private and public sectors.

PMID- 29346552
TI  - Safety profile of near-zero fluoroscopy atrial fibrillation ablation with non
      fluoroscopic catheter visualization: experience from 1000 consecutive procedures.
AB  - Aims: Efforts to reduce radiation exposure during catheter ablation procedures
      have included the use of various technological measures. Significant results have
      been achieved to the point where near lead-free procedures in routine clinical
      practice has become a realistic goal. The integration of MediGuide technology
      [non-fluoroscopic catheter visualization technology (NFCV)] and three-dimensional
      electroanatomical mapping is one of the methods developed in response to
      radiation reduction initiatives. We aimed to evaluate the impact of this NFCV
      technology on atrial fibrillation (AF) catheter ablation in terms of reduction in
      procedural and radiation time as well as safety aspects. Methods and results:
      Between March 2012 and March 2017, a total of 1000 patients underwent AF ablation
      using NFCV. Patient and procedural data and complications within the first 3
      months were entered into a prospective registry and analysed. We assessed
      procedure time, fluoroscopy time, and dose and complications. In a cohort of 1000
      patients (62.9 +/- 11 years; 72% men; left ventricular ejection fraction 57%; and
      left atrial diameter 43.2 mm), the median procedure time was 120 min, median
      fluoroscopy time was 0.90 min, and the median fluoroscopy dose of was 345.1 cGy .
      cm2. Stratification of the first (Group 1) and the last 250 (Group 2) cases
      showed significant improvement in the median procedure time (140-110 min) and
      reduction in the median fluoroscopy time (6-0.5 min) and the median dose (2263
      151.9 cGy . cm2). The overall complication rate was 2.0%. Conclusion: The use of
      NFCV technology enables safe, consistent, and 'near lead-free' performance of AF
      ablation in routine clinical practice.

PMID- 29346553
TI  - Prediction of Barrett's esophagus: are we there yet?

PMID- 29346554
TI  - Functional Roles of Sex-Biased, Growth Hormone-Regulated MicroRNAs miR-1948 and
      miR-802 in Young Adult Mouse Liver.
AB  - Sex-specific temporal patterns of pituitary growth hormone (GH) secretion
      determine the sex-biased transcription of hundreds of genes in the liver and
      impart important sex differences in liver physiology, metabolism, and disease.
      Sex differences in hepatic gene expression vary widely, ranging from less than
      twofold to >1000-fold in the mouse. Here, we use small RNA sequencing to discover
      24 sex-biased mouse liver microRNAs (miRNAs), and then investigate the roles of
      two of these miRNAs in GH-regulated liver sex differences. Studies in prepubertal
      and young adult mice, and in mice in which pituitary hormones are ablated or
      where sex-specific hepatic GH signaling is dysregulated, demonstrated that the
      male-biased miR-1948 and the female-biased miR-802 are both regulated by sex
      specific pituitary GH secretory patterns, acquire sex specificity at puberty, and
      are dependent on the GH-activated transcription factor STAT5 for their sex
      specific expression. Both miRNAs are within genomic regions characterized by sex
      biased chromatin accessibility. miR-1948, an uncharacterized miRNA, has essential
      features for correct Drosha/Dicer processing, generates a bona fide mature miRNA
      with strong strand bias for the 5p arm, and is bound by Argonaute in liver
      tissue, as is miR-802. In vivo studies using inhibitory locked nucleic acid
      sequences revealed that miR-1948-5p preferentially represses female-biased
      messenger RNAs (mRNAs) and induces male-biased mRNAs in male liver; conversely,
      miR-802-5p preferentially represses male-biased mRNAs and increases levels of
      female-biased mRNAs in female liver. Cytochrome P450 mRNAs were strongly enriched
      as targets of both miRNAs. Thus, miR-1948-5p and miR-802-5p are functional
      components of the GH regulatory network that shapes sex-differential gene
      expression in mouse liver.

PMID- 29346557
TI  - Peer supporters' experiences on an Australian perinatal mental health helpline.
AB  - Perinatal mental health is an important public health issue, and peer support is
      a potentially important strategy for emotional well-being in the perinatal
      period. PANDA Perinatal Anxiety & Depression Australia provides support to
      individuals impacted by perinatal mental health issues via the National Perinatal
      Anxiety & Depression Helpline. Callers receive peer support from volunteers and
      counselling from paid professional staff. The views and experiences of PANDA peer
      support volunteers have not previously been studied. We conducted two focus
      groups and an online survey to explore the experiences of women providing
      volunteer peer support on the Helpline. Data collection took place in October and
      November 2013. Two social theories were used in framing and addressing the study
      aims and in interpreting our findings: the Empathy-Altruism Hypothesis, and the
      Helper Therapy Principle. All PANDA volunteers were invited to participate (n =
      40). Eight volunteers attended a focus group, and 11 survey responses were
      received. Descriptive statistics were used to analyse quantitative data. All
      survey respondents 'strongly agreed' that they felt positive about being part of
      PANDA. Thematic analysis of data from focus groups and open-ended survey
      responses identified the following themes: motivated to help others, supported to
      support callers, helping to make a difference and emotional impacts for
      volunteers. Respondents described a strong desire to support others experiencing
      emotional distress as a motivator to volunteer. Although perinatal peer support
      services are designed to benefit those who receive support, this study suggests
      volunteers may also experience personal benefits from the role.

PMID- 29346556
TI  - Cohort Profile: The Epidemiology of Chronic Diseases and Multimorbidity. The
      EpiChron Cohort Study.

PMID- 29346555
TI  - Data Resource Profile: Expansion of the Rochester Epidemiology Project medical
      records-linkage system (E-REP).

PMID- 29346558
TI  - Thoraco-abdominal aortic aneurysm rupture in a patient with Shprintzen-Goldberg
      syndrome.
AB  - Shprintzen-Goldberg syndrome is a rare systemic connective tissue disorder
      characterized by craniosynostosis, skeletal abnormalities, infantile hypotonia,
      mild-to-moderate intellectual disability and cardiovascular anomalies. To our
      knowledge, this is the first report of a Shprintzen-Goldberg syndrome patient who
      developed a thoraco-abdominal aortic aneurysm. The aneurysm grew rapidly
      necessitating emergent thoraco-abdominal aortic replacement. The postoperative
      course was uneventful, and a careful lifetime follow-up was planned.

PMID- 29346560
TI  - Aggregation and travelling wave dynamics in a two-population model of cancer cell
      growth and invasion.
AB  - Cells adhere to each other and to the extracellular matrix (ECM) through protein
      molecules on the surface of the cells. The breaking and forming of adhesive
      bonds, a process critical in cancer invasion and metastasis, can be influenced by
      the mutation of cancer cells. In this paper, we develop a nonlocal mathematical
      model describing cancer cell invasion and movement as a result of integrin
      controlled cell-cell adhesion and cell-matrix adhesion, for two cancer cell
      populations with different levels of mutation. The partial differential equations
      for cell dynamics are coupled with ordinary differential equations describing the
      ECM degradation and the production and decay of integrins. We use this model to
      investigate the role of cancer mutation on the possibility of cancer clonal
      competition with alternating dominance, or even competitive exclusion (phenomena
      observed experimentally). We discuss different possible cell aggregation
      patterns, as well as travelling wave patterns. In regard to the travelling waves,
      we investigate the effect of cancer mutation rate on the speed of cancer
      invasion.

PMID- 29346561
TI  - Floricolin C elicits intracellular reactive oxygen species accumulation and
      disrupts mitochondria to exert fungicidal action.
AB  - Candida albicans, one of the most prevalent fungal pathogens, causes severe
      mucosal and invasive infections in predisposed individuals. The rise of fungal
      infection and drug resistance demands the development of novel antifungal agents.
      In this study, we observed that floricolin C (FC), a p-terphenyl pigment from an
      endolichenic fungus, killed C. albicans cells in the planktonic state or within
      biofilms through reactive oxygen species (ROS) accumulation. Further tests
      revealed that FC could directly damage the mitochondria to cause ROS
      accumulation. In addition, FC can quench thiol-based agents through a Michael
      reaction involving the alpha,beta-unsaturated carbonyl group, whose effect may
      chelate intracellular thiol-based molecules or proteins in C. albicans, resulting
      in an imbalance in redox homeostasis. Increased ROS generation led to
      mitochondrial dysfunction, nuclear dispersion and consequently cell death. We
      further demonstrated that FC could prevent biofilm formation of other Candida
      species and eradicate their pre-formed biofilms. An in vivo study demonstrated
      that FC prolonged the survival of C. albicans-infected Caenorhabditis elegans.
      Taken together, our study provides the basis for the application of FC to combat
      Candida infections.

PMID- 29346559
TI  - Predicting plant biomass accumulation from image-derived parameters.
AB  - Background: Image-based high-throughput phenotyping technologies have been
      rapidly developed in plant science recently, and they provide a great potential
      to gain more valuable information than traditionally destructive methods.
      Predicting plant biomass is regarded as a key purpose for plant breeders and
      ecologists. However, it is a great challenge to find a predictive biomass model
      across experiments. Results: In the present study, we constructed 4 predictive
      models to examine the quantitative relationship between image-based features and
      plant biomass accumulation. Our methodology has been applied to 3 consecutive
      barley (Hordeum vulgare) experiments with control and stress treatments. The
      results proved that plant biomass can be accurately predicted from image-based
      parameters using a random forest model. The high prediction accuracy based on
      this model will contribute to relieving the phenotyping bottleneck in biomass
      measurement in breeding applications. The prediction performance is still
      relatively high across experiments under similar conditions. The relative
      contribution of individual features for predicting biomass was further
      quantified, revealing new insights into the phenotypic determinants of the plant
      biomass outcome. Furthermore, methods could also be used to determine the most
      important image-based features related to plant biomass accumulation, which would
      be promising for subsequent genetic mapping to uncover the genetic basis of
      biomass. Conclusions: We have developed quantitative models to accurately predict
      plant biomass accumulation from image data. We anticipate that the analysis
      results will be useful to advance our views of the phenotypic determinants of
      plant biomass outcome, and the statistical methods can be broadly used for other
      plant species.

PMID- 29346562
TI  - Scaffold-free trachea regeneration by tissue engineering with bio-3D printing.
AB  - OBJECTIVES: Currently, most of the artificial airway organs still require
      scaffolds; however, such scaffolds exhibit several limitations. Alternatively,
      the use of an autologous artificial trachea without foreign materials and
      immunosuppressants may solve these issues and constitute a preferred tool. The
      rationale of this study was to develop a new scaffold-free approach for an
      artificial trachea using bio-3D printing technology. Here, we assessed the
      circumferential tracheal replacement using scaffold-free trachea-like grafts
      generated from isolated cells in an inbred animal model. METHODS: Chondrocytes
      and mesenchymal stem cells were isolated from F344 rats. Rat lung microvessel
      endothelial cells were purchased. Our bio-3D printer generates spheroids
      consisting of several types of cells to create 3D structures. The bio-3D-printed
      artificial trachea from spheroids was matured in a bioreactor and transplanted
      into F344 rats as a tracheal graft under general anaesthesia. The mechanical
      strength of the artificial trachea was measured, and histological and
      immunohistochemical examinations were performed. RESULTS: Tracheal
      transplantation was performed in 9 rats, which were followed up postoperatively
      for 23 days. The average tensile strength of artificial tracheas before
      transplantation was 526.3 +/- 125.7 mN. The bio-3D-printed scaffold-free
      artificial trachea had sufficient strength to transplant into the trachea with
      silicone stents that were used to prevent collapse of the artificial trachea and
      to support the graft until sufficient blood supply was obtained. Chondrogenesis
      and vasculogenesis were observed histologically. CONCLUSIONS: The scaffold-free
      isogenic artificial tracheas produced by a bio-3D printer could be utilized as
      tracheal grafts in rats.

PMID- 29346564
TI  - Genome-wide comparison of allele-specific gene expression between African and
      European populations.
AB  - Transcriptomic diversity across human populations reflects differential
      regulatory mechanisms. Allelic-imbalanced gene expression is a genetic regulatory
      mechanism that contributes to human phenotypic variation. To systematically
      investigate genome-wide allele-specific expression (ASE), we analyzed RNA-Seq
      data from European and African populations provided by the Geuvadis project. We
      identified 11 sites in 8 genes showing ASE in both Europeans and Africans, and 9
      sites in 9 genes showing population-specific ASE, including both novel and known
      ASE signals. Notably, the top signal of differentiated ASE between inter
      continental populations was observed in DNAJC15, of which the derived allele of
      rs12015, a single nucleotide polymorphism (SNP), showed significantly higher
      expression than did the ancestral allele specifically in European individuals. We
      identified a unique haplotype of DNAJC15, where a few SNPs highly differentiated
      between European and African populations were strongly linked to sites with high
      ASE. Among these, SNP rs17553284 affected the binding of several transcription
      factors as well as the genotype-dependent expression of DNAJC15. Therefore, we
      speculated that rs17553284 could be a regulatory causal variant that mediates the
      ASE of rs12015. We found several variations in ASE between intercontinental
      populations. The highly differentiated ASE genes identified here may implicate in
      the phenotypic variations among populations that are both evolutionarily and
      medically important.

PMID- 29346563
TI  - LC3 Immunostaining in the Inferior Olivary Nuclei of Cats With Niemann-Pick
      Disease Type C1 Is Associated With Patterned Purkinje Cell Loss.
AB  - The feline model of Niemann-Pick disease, type C1 (NPC1) recapitulates the
      clinical, neuropathological, and biochemical abnormalities present in children
      with NPC1. The hallmarks of disease are the lysosomal storage of unesterified
      cholesterol and multiple sphingolipids in neurons, and the spatial and temporal
      distribution of Purkinje cell death. In feline NPC1 brain, microtubule-associated
      protein 1 light chain 3 (LC3) accumulations, indicating autophagosomes, were
      found within axons and presynaptic terminals. High densities of accumulated LC3
      were seen in subdivisions of the inferior olive, which project to cerebellar
      regions that show the most Purkinje cell loss, suggesting that autophagic
      abnormalities in specific climbing fibers may contribute to the spatial pattern
      of Purkinje cell loss seen. Biweekly intrathecal administration of 2
      hydroxypropyl-beta cyclodextrin (HPbetaCD) ameliorated neurological dysfunction,
      reduced cholesterol and sphingolipid accumulation, and increased lifespan in NPC1
      cats. LC3 pathology was reduced in treated animals suggesting that HPbetaCD
      administration also ameliorates autophagic abnormalities. This study is the first
      to (i) identify specific brain regions exhibiting autophagic abnormalities in any
      species with NPC1, (ii) provide evidence of differential vulnerability among
      discrete brain nuclei and pathways, and (iii) show the amelioration of these
      abnormalities in NPC1 cats treated with HPbetaCD.

PMID- 29346565
TI  - Apigenin induces cell shrinkage in Candida albicans by membrane perturbation.
AB  - Apigenin, a natural flavone, has been well characterized for its their
      anticarcinogenic property; however, its bioactivity against pathogenic fungi has
      not been investigated in detail. In this study, we examined the antifungal
      activity and mode of action of apigenin. Apigenin inhibited the growth of fungal
      pathogens, which induced superficial infection and reduced biofilm mass. Three
      dimensional flow cytometric analysis demonstrated that apigenin induced
      morphological changes, especially cell shrinkage, in Candida albicans. We
      investigated the cause of cell shrinkage using the cyanine dye 3,3?
      dipropylthiacarbocyanine iodide. Results revealed that apigenin altered the cell
      membrane potential. Apigenin also induced membrane dysfunction, and increased
      cell permeability to 1,6-diphenyl-1,3,5-hexatriene and propidium iodide. We
      observed the influx and efflux of fluorescent molecules of varying molecular
      weights and radii across large unilamellar vesicles and live cells that had been
      treated with apigenin. Membrane disruption facilitates the release of small
      intracellular constituents such as ions and sugars, but not proteins. These
      findings suggested that apigenin exerted an antifungal activity by inducing
      membrane disturbances, which led to cell shrinkage and leakage of intracellular
      components.

PMID- 29346566
TI  - A genome-wide association study identifies nucleotide variants at SIGLEC5 and
      DEFA1A3 as risk loci for periodontitis.

PMID- 29346567
TI  - Epithelial grafting of a decellularized whole-tracheal segment: an in vivo
      experimental model.
AB  - OBJECTIVES: Prerequisites for successful trachea transplantation include the use
      of a biocompatible construct, submucosal vascularization and an epithelial
      covering. Implantation of non-epithelialized tracheal scaffolds may lead to
      stenosis. However, epithelial grafting or seeding can only be attempted onto a
      well-vascularized submucosal bed. Our aim was to investigate a method to prevent
      stenosis during prelamination of non-epithelialized, gently decellularized rabbit
      tracheae and to evaluate whether grafting of revascularized constructs with
      buccal mucosa is feasible. METHODS: Allotracheae underwent two 48-h cycles of
      detergent-enzymatic decellularization using sodium deoxycholate and DNAse. In the
      first series, 12 circular scaffolds were implanted bilaterally in lateral
      thoracic artery flaps (n = 6 rabbits). Right-sided transplants were covered
      internally with IntegraTM. In the second series, 10 decellularized tracheae
      covered with Integra were prelaminated in flaps (n = 10 rabbits). Twenty-one days
      after implantation, revascularized tracheae were grafted with buccal mucosa. A
      macroscopic, histological analysis and immunohistochemistry were performed on
      explants. RESULTS: In the first series, tracheae without Integra covering
      developed significantly greater intraluminal (P = 0.032) and subepithelial
      narrowing (P = 0.0345) compared with tracheae with Integra covering. All tracheae
      exhibited insufficient submucosal revascularization. In the second series,
      submucosal revascularization was incomplete in the first 2 constructs, which were
      implanted circularly. These tracheae only showed marginal buccal graft ingrowth.
      To accelerate revascularization, the subsequent 8 transplants were opened
      longitudinally before implantation. Compared to circularly implanted tracheae,
      submucosal revascularization of these transplants was superior (P = 0.0008).
      Graft adherence was complete in 6 opened constructs. Mild lymphocytic
      infiltration within the buccal graft was detected in 5 specimens. CONCLUSIONS: We
      observed satisfactory host integration of opened tracheae that were temporarily
      covered with Integra during revascularization and subsequently grafted with
      buccal mucosa. Integra successfully prevented stenosis during revascularization.
      This model may provide an example of an immunosuppressive-free approach in the
      treatment of long-segment tracheal lesions. With the aid of further refinements
      such as a respiratory epithelial lining, an orthotopically transplantable
      construct could be created.

PMID- 29346568
TI  - Are infection specialists recommending short antibiotic treatment durations? An
      ESCMID international cross-sectional survey.
AB  - Objectives: To evaluate the current practice and the willingness to shorten the
      duration of antibiotic therapy among infection specialists. Methods: Infection
      specialists giving at least weekly advice on antibiotic prescriptions were
      invited to participate in an online cross-sectional survey between September and
      December 2016. The questionnaire included 15 clinical vignettes corresponding to
      common clinical cases with favourable outcomes; part A asked about the antibiotic
      treatment duration they would usually advise to prescribers and part B asked
      about the shortest duration they were willing to recommend. Results: We included
      866 participants, mostly clinical microbiologists (22.8%, 197/863) or infectious
      diseases specialists (58.7%, 507/863), members of an antibiotic stewardship team
      in 73% (624/854) of the cases, coming from 58 countries on all continents. Thirty
      six percent of participants (271/749) already advised short durations of
      antibiotic therapy (compared with the literature) to prescribers for more than
      half of the vignettes and 47% (312/662) chose shorter durations in part B
      compared with part A for more than half of the vignettes. Twenty-two percent
      (192/861) of the participants declared that their regional/national guidelines
      expressed durations of antibiotic therapy for a specific clinical situation as a
      fixed duration as opposed to a range and in the multivariable analysis this was
      associated with respondents advising short durations for more than half of the
      vignettes (adjusted OR 1.5, P = 0.02). Conclusions: The majority of infection
      specialists currently do not advise the shortest possible duration of antibiotic
      therapy to prescribers. Promoting short durations among these experts is urgently
      needed.

PMID- 29346570
TI  - Implementation status of morbidity and mortality conferences in Swiss hospitals:
      a national cross-sectional survey study.
AB  - Objective: To determine the implementation status and current practice of
      morbidity and mortality conferences (M&MCs) in Switzerland. Design: A national
      cross-sectional online survey was conducted in spring 2017. The questionnaire
      focused on overall goals, structure and procedures of hospital M&MCs. Further
      topics included satisfaction, perceived effectiveness and support requirements.
      Setting: A total of 913 chief physicians of surgery and internal medicine, and
      specialist fields of obstetrics and gynaecology, anaesthesiology and intensive
      care from Swiss acute care hospitals were invited to the survey. 321 completed
      the questionnaire, resulting in a 35.2% response rate. Participants: Chief or
      senior physicians in charge of the M&MCs in their department. Intervention: No
      intervention. Main Outcome Measures: Numbers and percentages of M&MCs within the
      surveyed disciplines fulfilling certain characteristics and procedural features.
      Results: Among 321 respondents, the majority are conducting M&MCs in their
      departments. Within and between the medical disciplines considerable
      heterogeneity was found in structural and procedural features of M&MCs. Only a
      small part of the reported M&MCs is following a systematic approach and meeting
      recommended procedural features. Although the respondents are satisfied and
      perceive the M&MCs as an efficient tool, they agree that there is a need for
      professionalization and standardization. Conclusion: M&MCs are widely used to
      promote medical education, patient safety and quality improvements. However, the
      term M&MC seems to cover different types of meetings. Although the overall goals
      are similar, various types of M&MCs are used in practice and different objectives
      are pursued. Tools such as checklists, guidelines and templates are considered
      helpful.

PMID- 29346569
TI  - Controlled Antenatal Thyroid Screening II: Effect of Treating Maternal Suboptimal
      Thyroid Function on Child Cognition.
AB  - Context and Objective: The Controlled Antenatal Thyroid Screening (CATS) study
      investigated treatment of suboptimal gestational thyroid function (SGTF) on
      childhood cognition and found no difference in intelligence quotient (IQ) at 3
      years between children of treated and untreated SGTF mothers. We have measured IQ
      in the same children at age 9.5 years and included children from normal
      gestational thyroid function (normal-GTF) mothers. Design, Setting, and
      Participants: One examiner, blinded to participant group, assessed children's IQ
      (Wechsler Intelligence Scale for Children, Fourth Edition UK), long-term memory,
      and motor function (Developmental Neuropsychological Assessment II) from children
      of 119 treated and 98 untreated SGTF mothers plus children of 232 mothers with
      normal-GTF. Logistic regression explored the odds and percentages of an IQ < 85
      in the groups. Results: There was no difference in IQ < 85 between children of
      mothers with normal-GTF and combined SGTF, i.e., treated and untreated (fully
      adjusted odds ratio [OR] = 1.15 [95% confidence interval (CI) 0.52, 2.51]; P =
      0.731). Furthermore, there was no significant effect of treatment [untreated OR =
      1.33 (95% CI 0.53, 3.34); treated OR = 0.75 (95% CI 0.27, 2.06) P = 0.576]. IQ <
      85 was 6.03% in normal-GTF, 7.56% in treated, and 11.22% in untreated groups.
      Analyses accounting for treated-SGTF women with free thyroxine > 97.5th
      percentile of the entire CATS-I cohort revealed no significant effect on a
      child's IQ < 85 in CATS-II. IQ at age 3 predicted IQ at age 9.5 (P < 0.0001) and
      accounted for 45% of the variation. Conclusions: Maternal thyroxine during
      pregnancy did not improve child cognition at age 9.5 years. Our findings
      confirmed CATS-I and suggest that the lack of treatment effect may be a result of
      the similar proportion of IQ < 85 in children of women with normal-GTF and SGTF.

PMID- 29346571
TI  - Natural Course of Human T-Cell Leukemia Virus Type 1 Proviral DNA Levels in
      Carriers During Pregnancy.
AB  - The measurement of human T-cell leukemia virus type 1 (HTLV-1) proviral DNA
      levels by using polymerase chain reaction has been beneficial for confirming HTLV
      1 infection during pregnancy. However, the influence of pregnancy on HTLV-1
      infection and proviral DNA levels among pregnant women with HTLV-1 has not been
      clarified. We prospectively gathered blood samples from 36 pregnant women in whom
      HTLV-1 carriage was previously diagnosed and sequentially measured their proviral
      DNA levels. The HTLV-1 proviral DNA levels remained at a plateau during pregnancy
      but were elevated after delivery. Moreover, flow cytometry and serological
      analyses revealed that the regulatory T-cell population and soluble interleukin 2
      receptor levels were similarly elevated after birth in comparison with those in
      control pregnant women. This study is the first to provide data on sequential
      changes in HTLV-1 proviral DNA levels during and after pregnancy. These findings
      will guide the establishment of a better program to prevent mother-to-child
      transmission of HTLV-1.

PMID- 29346572
TI  - Analysis of experience-regulated transcriptome and imprintome during critical
      periods of mouse visual system development reveals spatiotemporal dynamics.
AB  - Visual system development is light-experience dependent, which strongly
      implicates epigenetic mechanisms in light-regulated maturation. Among many
      epigenetic processes, genomic imprinting is an epigenetic mechanism through which
      monoallelic gene expression occurs in a parent-of-origin-specific manner. It is
      unknown if genomic imprinting contributes to visual system development. We
      profiled the transcriptome and imprintome during critical periods of mouse visual
      system development under normal- and dark-rearing conditions using B6/CAST F1
      hybrid mice. We identified experience-regulated, isoform-specific and brain
      region-specific imprinted genes. We also found imprinted microRNAs were
      predominantly clustered into the Dlk1-Dio3 imprinted locus with light experience
      affecting some imprinted miRNA expression. Our findings provide the first
      comprehensive analysis of light-experience regulation of the transcriptome and
      imprintome during critical periods of visual system development. Our results may
      contribute to therapeutic strategies for visual impairments and circadian rhythm
      disorders resulting from a dysfunctional imprintome.

PMID- 29346573
TI  - The Addition of Bevacizumab to Oxaliplatin-Based Chemotherapy: Impact Upon
      Hepatic Sinusoidal Injury and Thrombocytopenia.
AB  - Background: Oxaliplatin-based chemotherapy can cause hepatic sinusoidal injury
      (HSI), portal hypertension, and splenic sequestration of platelets. Evidence
      suggests that bevacizumab may protect against HSI. Methods: Two cohorts of
      metastatic colorectal cancer (CRC) were analyzed: a nonrandomized exploratory
      cohort of 184 patients treated at a single institution from 2003 to 2010 and a
      confirmatory cohort of 200 patients from a multi-institutional randomized trial
      (NO16966). All patients were treated with frontline fluoropyrimidine and
      oxaliplatin with or without bevacizumab. Changes in splenic volumes and platelet
      counts were compared by treatment, two-sided log-rank test. Results: In the
      exploratory cohort, the bevacizumab-treated patients (n = 138) compared with the
      nonbevacizumab-treated patients (n = 46) demonstrated a longer median time to
      splenic enlargement (>=30%, P = .02) and reduced rate of thrombocytopenia (<150
      000/mm3, P = .04). In the confirmatory cohort (106 bevacizumab arm and 94 placebo
      arm), the median time to a spleen enlargement of 30% or more was 7.6 vs 5.4 (P =
      .01), and six-month cumulative incidence of thrombocytopenia (platelets < 100
      000/mm3) was 19% vs 51% (P < .001) for bevacizumab compared with placebo. The
      development of an increasing spleen size was associated with the risk of either
      grade 1 or grade 2 thrombocytopenia (P < .001). The cumulative rate of grade 1 or
      grade 2 thrombocytopenia was statistically less in the bevacizumab arm, with six
      month grade 2 thrombocytopenia rates of 4% vs 23% (P < .001). Patients with a
      large spleen prior to chemotherapy initiation appeared to be at highest risk of
      this toxicity. Conclusion: In metastatic CRC, the addition of bevacizumab to
      oxaliplatin-based chemotherapy reduces the frequency of splenic enlargement and
      the rate of thrombocytopenia.

PMID- 29346574
TI  - Systematic genetic interaction studies identify histone demethylase Utx as
      potential target for ameliorating Huntington's disease.

PMID- 29346575
TI  - Abacavir Induces Arterial Thrombosis in a Murine Model.
AB  - Background: The purinergic system is known to underlie prothrombotic and
      proinflammatory vascular programs, making the profile of experimental actions
      demonstrated by abacavir compatible with thrombogenesis. However, direct evidence
      of a prothrombotic effect by the drug has been lacking. Methods: The present
      study appraised the effects of abacavir in a well-validated animal model of
      arterial thrombosis. The role of ATP-P2X7 receptors in the actions of the drug
      was also assessed, and the actions of recognized vascular-damaging agents and
      other nucleoside reverse-transcriptase inhibitors (NRTIs) were evaluated and
      compared to those of abacavir. Results: Abacavir dose-dependently promoted
      thrombus formation. This effect was reversed by a P2X7-receptor antagonist and
      was nonexistent in P2X7 knockout mice. The effects of abacavir were similar to
      those of diclofenac and rofecoxib. Other NRTIs had no thrombosis-related effects.
      Conclusion: Abacavir promotes arterial thrombosis through interference with
      purinergic signaling, suggesting a possible biological mechanism for the clinical
      association of abacavir with cardiovascular diseases.

PMID- 29346576
TI  - Commentary on 'Communicating Messages About Drinking': Using the 'Big Legal Guns'
      to Block Alcohol Health Warning Labels.
AB  - Like the tobacco industry, the alcohol industry, with the support of governments
      in alcohol exporting nations, is looking to international trade and investment
      law as a means to oppose health warning labels on alcohol. The threat of such
      litigation, let alone its commencement, has the potential to deter all but the
      most resolute governments from implementing health warning labeling.

PMID- 29346577
TI  - Improved Success Rate of Arterial Puncture for Blood Gas Analysis Through
      Standardization.
AB  - Background: Arterial puncture for blood gas analysis is a common procedure in
      hospitals. The aim of the study is to determine if standardizing technique
      elements of the arterial puncture process could improve the success rate of
      technicians through the full scope of an academic medical center. Methods: The
      study is conducted by the Blood Gas Laboratory at University of Utah Health's
      main campus. During the baseline period, technicians tallied whether arterial
      puncture attempts were successful or unsuccessful from December 2014 through
      February 2015. A small team reviewed the steps of performing arterial puncture
      and selected segments of the process for standardization. Starting in March 2015,
      staff were trained individually in the standard processes. All staff continued to
      tally outcomes of puncture attempts through March 2017. Results: During the
      baseline period, the puncture success rate was 83.6%. From April 2015 through
      March 2017 the success rate was 89.2%. Conclusion: Standardizing arterial
      puncture technique for blood gas analysis leads to fewer punctures.

PMID- 29346578
TI  - Effect of daidzein and equol on DNA replication in MCF-7 cells.
AB  - It has been reported that daidzein and equol stimulate DNA replication and
      proliferation of MCF-7 cells. However, their molecular mechanisms of action are
      still unclear. We examined the effects of daidzein and equol on DNA replication
      of MCF-7 cells, focusing on MCM2-7 proteins, which function as the replicative
      helicase. In the presence of either 1 MUM of daidzein or equol, the number of
      cells in S-phase, which was determined by detecting bromodeoxyuridine
      incorporated into replicated DNA, almost doubled. The total amounts of MCM7
      protein and chromatin-bound MCM7 protein increased in the presence of daidzein.
      The data suggest that phytoestrogens facilitate cell cycle progression in G1
      phase by increasing the level of MCM proteins. In the presence of phytoestrogens,
      phosphorylation of Rb and levels of MCM2, 3 and 7 mRNA increased, suggesting that
      stimulation of MCM2-7 transcription is involved in the cell cycle progression.
      Under the same conditions, double-stranded DNA breakage in logarithmically
      growing MCF-7 cells, which was detected using anti-gamma-H2AX antibodies, did not
      increase in the presence of equol.

PMID- 29346579
TI  - Web-Based Cognitive Behavior Therapy for Chronic Pain Patients with Aberrant Drug
      Related Behavior: Outcomes from a Randomized Controlled Trial.
AB  - Objective: There is high unmet need for effective behavioral treatments for
      chronic pain patients at risk for or with demonstrated histories of opioid
      misuse. Despite growing evidence supporting technology-based delivery of self
      management interventions for chronic pain, very few such programs target co
      occurring chronic pain and aberrant drug-related behavior. This randomized
      controlled trial evaluated the effectiveness of a novel, web-based self
      management intervention, grounded in cognitive behavior therapy, for chronic pain
      patients with aberrant drug-related behavior. Methods: Opioid-treated chronic
      pain patients at a specialty pain practice who screened positive for aberrant
      drug-related behavior (N = 110) were randomized to receive treatment as usual
      plus the web-based program or treatment as usual alone. The primary outcomes of
      pain severity, pain interference, and aberrant drug-related behavior, and the
      secondary outcomes of pain catastrophizing and pain-related emergency department
      visits, were assessed during the 12-week intervention and at one and three months
      postintervention. Results: Patients assigned to use the web-based program
      reported significantly greater reductions in aberrant drug-related behavior, pain
      catastrophizing, and pain-related emergency department visits-but not pain
      severity or pain interference-relative to those assigned to treatment as usual.
      The positive outcomes were observed during the 12-week intervention and for three
      months postintervention. Conclusions: A web-based self-management program, when
      delivered in conjunction with standard specialty pain treatment, was effective in
      reducing chronic pain patients' aberrant drug-related behavior, pain
      catastrophizing, and emergency department visits for pain. Technology-based self
      management tools may be a promising therapeutic approach for the vulnerable group
      of chronic pain patients who have problems managing their opioid medication.

PMID- 29346581
TI  - Melatonin attenuates lung ischaemia-reperfusion injury via inhibition of
      oxidative stress and inflammation.
AB  - OBJECTIVES: Lung ischaemia-reperfusion injury is a complex pathophysiological
      process due to the production of reactive oxygen species and the generation of
      inflammatory reaction. We investigated the protective effects and the
      corresponding mechanism of melatonin (MT), a potent free-radical scavenger, on
      lung injury induced by ischaemia-reperfusion in a mouse model. METHODS: Adult
      male C57BL/6J mice (n = 30) were randomly and equally allocated into 5 groups:
      sham controls, IR, IR + 10 mg/kg MT, IR + 20 mg/kg MT and IR + 30 mg/kg MT. Lung
      ischaemia-reperfusion injury was induced by thoracotomy followed by clamping of
      the left hilum for 1 h and subsequent reperfusion for 2 h. RESULTS: Histological
      scoring analysis showed that lung parenchymal damage was ameliorated in the
      melatonin pretreatment groups when compared with the IR group, with the IR + 20
      mg/kg MT group showing the strongest effect among the melatonin pretreatment
      groups. Wet-to-dry weight ratio, detection of malondialdehyde, protein
      expressions of inflammatory factors (tumour necrosis factor-alpha, interleukin
      1beta, NF-kappaB and IKK-gamma) and apoptotic factors (cleaved caspase-3 and
      Bax/Bcl-2), as well as TUNEL assay showed changes similar to those of the lung
      injury scores in all groups. In contrast, the examination of superoxide dismutase
      showed a pattern contrary to that of the lung injury score in all groups. In
      addition, immunohistochemistry staining showed that the expressions of the
      antioxidants glutathione peroxidase and glutathione reductase were increased in
      the melatonin pretreatment groups. CONCLUSIONS: This study demonstrated that
      melatonin pretreatment attenuated lung ischaemia-reperfusion injury via
      inhibition of oxidative stress, inflammation and apoptosis.

PMID- 29346582
TI  - It's not just 'What' you do, it's also the 'Way' that you do it: Patient and
      Public Involvement in the Development of Health Research.
AB  - Purpose: This article presents a reflective account of Patient and Public
      Involvement (PPI) in the development of obesity and binge eating research.
      Method: We established Patient Advisory Groups (PAGs) at two English regional
      National Health Service (NHS) weight management services. PPI was evaluated as
      follows: (i) PAG members completed a Post Participation Evaluation Questionnaire,
      (ii) PAG meetings captured group discussion on PPI involvement, (iii)
      practitioner and researchers produced written reflections on PPI and (iv) sources
      one to three were consolidated during reflections that took place via e-mail and
      telephone correspondence between researchers and practitioners, culminating in a
      summary SKYPE meeting between one practitioner and one researcher involved in the
      PAGs. Results: Results in the form of reflections suggest guidelines on
      undertaking PPI were helpful with regard 'what to do', but less helpful on 'how'.
      For example, suggestions for the management of interpersonal factors such as
      eliciting self-disclosure and managing power differentials are insufficiently
      addressed in existing guidelines. Conclusions: The present case study illustrated
      how interpersonal considerations can help or hinder the optimal use of PPI.
      Recommendations for practitioners and researchers planning PPI are offered.

PMID- 29346580
TI  - Smoking, Sex, and Non-Small Cell Lung Cancer: Steroid Hormone Receptors in Tumor
      Tissue (S0424).
AB  - Background: To what extent steroid hormones contribute to lung cancer in male and
      female never smokers and smokers is unclear. We examined expression of hormone
      receptors in lung tumors by sex and smoking. Methods: Patients with primary non
      small cell lung cancer were recruited into an Intergroup study in the United
      States and Canada, led by SWOG (S0424). Tumors from 813 cases (450 women and 363
      men) were assayed using immunohistochemistry for estrogen receptor (ER)-alpha, ER
      beta, progesterone receptor (PR), and human epidermal growth factor receptor 2
      (HER2). Linear regression was used to examine differences in expression by sex
      and smoking status. Cox proportional hazard models were used to estimate survival
      associated with the receptors. All statistical tests were two-sided. Results: In
      ever smokers, postmenopause and oral contraceptive use were associated with lower
      nuclear ER-beta (P = .02) and total (nuclear + cytoplasmic) PR expression (P =
      .02), respectively. Women had lower cytoplasmic ER-alpha (regression coefficient
      [beta], or differences in H-scores = -15.8, P = .003) and nuclear ER-beta (beta =
      -12.8, P = .04) expression than men, adjusting for age, race, and smoking. Ever
      smokers had both higher cytoplasmic ER-alpha (beta = 45.0, P < .001) and ER-beta
      (beta = 25.9, P < .001) but lower total PR (beta = -42.1, P < .001) than never
      smokers. Higher cytoplasmic ER-alpha and ER-beta were associated with worse
      survival (hazard ratio = 1.73, 95% confidence interval [CI] = 1.15 to 2.58, and
      HR = 1.59, 95% CI = 1.08 to 2.33, respectively; quartiles 4 vs 1). Conclusions:
      Lower expression of nuclear ER-beta in women supports the estrogen hypothesis in
      lung cancer etiology. Increasing cytoplasmic ER-alpha and ER-beta and decreasing
      PR protein expression may be mechanisms whereby smoking disrupts hormone
      pathways.

PMID- 29346583
TI  - DataMed - an open source discovery index for finding biomedical datasets.
AB  - Objective: Finding relevant datasets is important for promoting data reuse in the
      biomedical domain, but it is challenging given the volume and complexity of
      biomedical data. Here we describe the development of an open source biomedical
      data discovery system called DataMed, with the goal of promoting the building of
      additional data indexes in the biomedical domain. Materials and Methods: DataMed,
      which can efficiently index and search diverse types of biomedical datasets
      across repositories, is developed through the National Institutes of Health
      funded biomedical and healthCAre Data Discovery Index Ecosystem (bioCADDIE)
      consortium. It consists of 2 main components: (1) a data ingestion pipeline that
      collects and transforms original metadata information to a unified metadata
      model, called DatA Tag Suite (DATS), and (2) a search engine that finds relevant
      datasets based on user-entered queries. In addition to describing its
      architecture and techniques, we evaluated individual components within DataMed,
      including the accuracy of the ingestion pipeline, the prevalence of the DATS
      model across repositories, and the overall performance of the dataset retrieval
      engine. Results and Conclusion: Our manual review shows that the ingestion
      pipeline could achieve an accuracy of 90% and core elements of DATS had varied
      frequency across repositories. On a manually curated benchmark dataset, the
      DataMed search engine achieved an inferred average precision of 0.2033 and a
      precision at 10 (P@10, the number of relevant results in the top 10 search
      results) of 0.6022, by implementing advanced natural language processing and
      terminology services. Currently, we have made the DataMed system publically
      available as an open source package for the biomedical community.

PMID- 29346584
TI  - In vitro interactions between IAP antagonist AT406 and azoles against planktonic
      cells and biofilms of pathogenic fungi Candida albicans and Exophiala
      dermatitidis.
AB  - In vitro interactions of AT406, a novel IAP antagonist, and azoles including
      itraconazole, voriconazole, and fluconazole against planktonic cells and biofilms
      of Candida albicans and Exophiala dermatitidis were assessed via broth
      microdilution checkerboard technique. AT406 alone exhibited limited antifungal
      activity. However, synergistic effect between AT406 and fluconazole was observed
      against both planktonic cells and biofilms of C. albicans, including one
      fluconazole-resistant strain. Moreover, synergism was also demonstrated between
      AT406 and itraconazole against both planktonic cells and biofilms of E.
      dermatitidis. No interaction was observed between AT406 and voriconazole. No
      antagonism was observed in all combinations.

PMID- 29346585
TI  - Maternal Vaccination With a Monocomponent Pertussis Toxoid Vaccine Is Sufficient
      to Protect Infants in a Baboon Model of Whooping Cough.
AB  - Background: Bordetella pertussis is a human pathogen responsible for serious
      respiratory illness. The disease is most severe in infants too young to be
      vaccinated with most hospitalizations and deaths occurring within this age group.
      The Advisory Committee on Immunization Practices recommended immunization of
      pregnant women to protect infants from birth until their first vaccination at 6-8
      weeks of age. We previously demonstrated that maternal vaccination with licensed
      acellular pertussis vaccines protected newborn baboons from disease. We
      hypothesized that protection was due to toxin-neutralizing, maternal anti
      pertussis toxin antibodies and predicted that maternal vaccination with a
      pertussis toxoid (PTx)-only vaccine would protect newborns from disease. Methods:
      Infant baboons born to unvaccinated mothers or mothers vaccinated with a PTx-only
      vaccine were challenged with B. pertussis at 5 weeks of age and followed for
      infection and signs of disease. Results: Although all challenged infants were
      heavily colonized, the infant baboons born to mothers vaccinated with PTx-only
      vaccine were free from clinical disease following exposure to B. pertussis. In
      contrast, disease was observed in infants born to unvaccinated mothers.
      Conclusions: Our results demonstrated that maternal vaccination with a PTx-only
      vaccine is sufficient to protect newborn baboons from disease following exposure
      to pertussis.

PMID- 29346586
TI  - PlasFlow: predicting plasmid sequences in metagenomic data using genome
      signatures.
AB  - Plasmids are mobile genetics elements that play an important role in the
      environmental adaptation of microorganisms. Although plasmids are usually
      analyzed in cultured microorganisms, there is a need for methods that allow for
      the analysis of pools of plasmids (plasmidomes) in environmental samples. To that
      end, several molecular biology and bioinformatics methods have been developed;
      however, they are limited to environments with low diversity and cannot recover
      large plasmids. Here, we present PlasFlow, a novel tool based on genomic
      signatures that employs a neural network approach for identification of bacterial
      plasmid sequences in environmental samples. PlasFlow can recover plasmid
      sequences from assembled metagenomes without any prior knowledge of the
      taxonomical or functional composition of samples with an accuracy up to 96%. It
      can also recover sequences of both circular and linear plasmids and can perform
      initial taxonomical classification of sequences. Compared to other currently
      available tools, PlasFlow demonstrated significantly better performance on test
      datasets. Analysis of two samples from heavy metal-contaminated microbial mats
      revealed that plasmids may constitute an important fraction of their metagenomes
      and carry genes involved in heavy-metal homeostasis, proving the pivotal role of
      plasmids in microorganism adaptation to environmental conditions.

PMID- 29346587
TI  - Are root cause analyses recommendations effective and sustainable? An
      observational study.
AB  - Objective: To assess the strength of root cause analysis (RCA) recommendations
      and their perceived levels of effectiveness and sustainability. Design: All RCAs
      related to sentinel events (SEs) undertaken between the years 2010 and 2015 in
      the public health system in Victoria, Australia were analysed. The type and
      strength of each recommendation in the RCA reports were coded by an expert
      patient safety classifier using the US Department of Veteran Affairs type and
      strength criteria. Participants and setting: Thirty-six public health services.
      Main outcome measure(s): The proportion of RCA recommendations which were
      classified as 'strong' (more likely to be effective and sustainable), 'medium'
      (possibly effective and sustainable) or 'weak' (less likely to be effective and
      sustainable). Results: There were 227 RCAs in the period of study. In these RCAs,
      1137 recommendations were made. Of these 8% were 'strong', 44% 'medium' and 48%
      were 'weak'. In 31 RCAs, or nearly 15%, only weak recommendations were made. In
      24 (11%) RCAs five or more weak recommendations were made. In 165 (72%) RCAs no
      strong recommendations were made. The most frequent recommendation types were
      reviewing or enhancing a policy/guideline/documentation, and training and
      education. Conclusions: Only a small proportion of recommendations arising from
      RCAs in Victoria are 'strong'. This suggests that insights from the majority of
      RCAs are not likely to inform practice or process improvements. Suggested
      improvements include more human factors expertise and independence in
      investigations, more extensive application of existing tools that assist teams to
      prioritize recommendations that are likely to be effective, and greater use of
      observational and simulation techniques to understand the underlying systems
      factors. Time spent in repeatedly investigating similar incidents may be better
      spent aggregating and thematically analysing existing sources of information
      about patient safety.

PMID- 29346589
TI  - Urban Evolutionary Ecology and the Potential Benefits of Implementing Genomics.
AB  - Urban habitats are quickly becoming exceptional models to address adaptation
      under rapid environmental change, given the expansive temporal and spatial scales
      with which anthropogenic landscape conversion occurs. Urban ecologists in the
      last 10-15 years have done an extraordinary job of highlighting phenotypic
      patterns that correspond with urban living, as well as delineating urban
      population structure using traditional genetic markers. The underpinning genetic
      mechanisms that govern those phenotypic patterns, however, are less well
      established. Moreover, the power of traditional molecular studies is constrained
      by the number of markers being evaluated, which limits the potential to assess
      fine-scale population structure potentially common in urban areas. With the
      recent proliferation of low-cost, high-throughput sequencing methods, we can
      begin to address an emerging question in urban ecology: are species adapted to
      local optima within cities or are they expressing latent phenotypic plasticity?
      Here, I provide a comprehensive review of previous urban ecological studies, with
      special focus on the molecular ecology and phenotypic adjustments documented in
      urban terrestrial and amphibious fauna. I subsequently pinpoint areas in the
      literature that could benefit from a genomic investigation and briefly discuss
      the suitability of specific techniques in addressing eco-evolutionary questions
      within urban ecology. Though many challenges exist with implementing genomics
      into urban ecology, such studies provide an exceptional opportunity to advance
      our understanding of eco-evolutionary processes in metropolitan areas.

PMID- 29346590
TI  - Hellenic Society of Cardiology International Congress 2017.

PMID- 29346588
TI  - Genome Sequencing of Museum Specimens Reveals Rapid Changes in the Genetic
      Composition of Honey Bees in California.
AB  - The western honey bee, Apis mellifera, is an enormously influential pollinator in
      both natural and managed ecosystems. In North America, this species has been
      introduced numerous times from a variety of different source populations in
      Europe and Africa. Since then, feral populations have expanded into many
      different environments across their broad introduced range. Here, we used whole
      genome sequencing of historical museum specimens and newly collected modern
      populations from California (USA) to analyze the impact of demography and
      selection on introduced populations during the past 105 years. We find that
      populations from both northern and southern California exhibit pronounced genetic
      changes, but have changed in different ways. In northern populations, honey bees
      underwent a substantial shift from western European to eastern European ancestry
      since the 1960s, whereas southern populations are dominated by the introgression
      of Africanized genomes during the past two decades. Additionally, we identify an
      isolated island population that has experienced comparatively little change over
      a large time span. Fine-scale comparison of different populations and time points
      also revealed SNPs that differ in frequency, highlighting a number of genes that
      may be important for recent adaptations in these introduced populations.

PMID- 29346591
TI  - Eduardo Marban MD PhD.

PMID- 29346593
TI  - HEART Group meeting.

PMID- 29346592
TI  - The ESC DAPT Guidelines 2017.

PMID- 29346594
TI  - The heart in embryology.

PMID- 29346595
TI  - 'Ten Commandments' of the 2017 ESC DAPT focused update Guidelines.

PMID- 29346596
TI  - Dual antiplatelet therapy: how, how long, and in which patients?

PMID- 29346597
TI  - Exenatide Increases IL-1RA Concentration and Induces Nrf-2-Keap-1-Regulated
      Antioxidant Enzymes: Relevance to beta-Cell Function.
AB  - Purpose: We previously demonstrated the anti-inflammatory and antioxidant effects
      of exenatide. We now hypothesized that exenatide also increases the plasma
      concentration of interleukin-1 receptor antagonist (IL-1RA), an endogenous anti
      inflammatory protein, and modulates the nuclear factor erythroid 2-related factor
      Kelchlike ECH-associated protein 1-antioxidant response element (Nrf-2-Keap-1
      ARE) system to induce key antioxidant enzymes to suppress inflammatory and
      oxidative stress. Methods: Twenty-four patients with obesity and type 2 diabetes
      receiving combined oral and insulin therapy were randomly assigned to receive
      either exenatide 10 MUg or placebo twice a day for 12 weeks. Results: Exenatide
      increased IL-1RA concentration by 61% (from 318 +/- 53 to 456 +/- 88 pg/mL; P <
      0.05). Exenatide treatment also suppressed Keap-1 protein (P < 0.05) and
      increased messenger RNA expression of NQO-1, glutathione S-transferase PI, heme
      oxygenase-1, and p21 and increased NAD(P)H dehydrogenase [quinone] 1 protein (P <
      0.05) in mononuclear cells. Conclusions: Because IL-1RA protects, maintains, and
      stimulates beta-cell function in humans and Nrf-2-Keap-1-ARE protects beta cells
      in animals with experimental diabetes, these actions of exenatide may contribute
      to a potential protective effect on beta cells in diabetes.

PMID- 29346598
TI  - Accuracy of preoperative staging for a priori resectable esophageal cancer.
AB  - This study assessed the accuracy of preoperative staging in patients undergoing
      oncological esophagectomy for adenocarcinoma and squamous cell carcinoma. All
      patients undergoing surgery for resectable esophageal cancer in a university
      hospital from 2005 to 2016 were identified from our institutional database.
      Patients with neoadjuvant treatment were excluded to avoid bias from down-staging
      effects. Routinely, all patients had an upper endoscopy with biopsy, a
      thoracoabdominal CT scan, an 18-FEG PET-CT, and endoscopic ultrasound.
      Preoperative staging was compared to histopathological staging of surgical
      specimen that was considered as gold standard. There were 51 patients with a
      median age of 65 years (IQR: 59.3-73 years) having 21 squamous cell carcinoma and
      30 adenocarcinoma, respectively. T- and N-stages were correctly predicted in 26
      (51%) and 37 patients (72%), respectively. Overall, 18 patients (35%) were
      preoperatively diagnosed with a correct T- and N-stage. There was no difference
      between adenocarcinoma and squamous cell carcinoma. Accuracy of the T-stage was
      not influenced by the smoking status. The N-stage was not correct in 7/22 smoking
      patients (32%) and 6/29 nonsmoking patients (21%).The N-stage was underestimated
      in smoking patients as 6/22 patients (27%) had a histologically confirmed N+ who
      were preoperatively classified as N0. In conclusion, only 35% of patients had a
      correct assessment. Separate T- and N-stage prediction was improved with 51% and
      72%, respectively. Major efforts are needed for improvement.

PMID- 29346599
TI  - Magnetic Resonance Imaging-Guided Laser Interstitial Thermal Therapy for the
      Treatment of Hypothalamic Hamartomas: A Retrospective Review.
AB  - BACKGROUND: Hypothalamic hamartomas (HH) are rare lesions associated with
      treatment-resistant epilepsy. Open surgery results in modest seizure control
      (about 50%) but has a significant associated morbidity. Radiosurgery is limited
      to a subset of patients due to latent therapeutic effects. Magnetic resonance
      imaging-guided laser interstitial thermal therapy (LITT) offers a novel minimally
      invasive option. OBJECTIVE: To evaluate a single center's outcomes for the LITT
      treatment of HH. METHODS: We retrospectively reviewed our experience with LITT
      for the treatment of HH using our institution's prospectively maintained patient
      database. RESULTS: Eighteen patients (mean age, 21.1 yr; median age, 11 yr)
      underwent 21 total LITT treatments for HH. Mean follow-up was 17.4 mo. The length
      of stay was 1 night for 16 (89%) patients. At the end of follow-up, 11 of 18
      patients (61%) had full disconnection of the HH, and 12 of 15 (80%) patients with
      gelastic seizures and 5 (56%) of 9 patients with nongelastic seizures were
      seizure free (International League Against Epilepsy Class 1). Immediate
      complications included a 39% (7/18) incidence of neurological deficits, including
      1 case of hemiparesis. At the end of follow-up, 22% of patients (4/18) had
      persistent deficits. The hypothyroidism that occurred was delayed in 11% of
      patients (2/18), as was short-term memory loss (22%, 4/18) and weight gain (22%,
      4/18). CONCLUSION: LITT therapy for HH can achieve excellent rates of seizure
      control with low morbidity and a short postoperative stay in a majority of
      patients. Additional research is needed to assess the durability of results and
      the full spectrum of cognitive outcomes.

PMID- 29346600
TI  - PD-1 blockade in HIV-infected patients with lung cancer: a new challenge or
      already a strategy?

PMID- 29346601
TI  - Accumulation of Mutational Load at the Edges of a Species Range.
AB  - Why species have geographically restricted distributions is an unresolved
      question in ecology and evolutionary biology. Here, we test a new explanation
      that mutation accumulation due to small population size or a history of range
      expansion can contribute to restricting distributions by reducing population
      growth rate at the edge. We examined genomic diversity and mutational load across
      the entire geographic range of the North American plant Arabidopsis lyrata,
      including old, isolated populations predominantly at the southern edge and
      regions of postglacial range expansion at the northern and southern edges.
      Genomic diversity in intergenic regions declined toward distribution edges and
      signatures of mutational load in exon regions increased. Genomic signatures of
      mutational load were highly linked to phenotypically expressed load, measured as
      reduced performance of individual plants and lower estimated rate of population
      growth. The geographic pattern of load and the connection between load and
      population growth demonstrate that mutation accumulation reduces fitness at the
      edge and helps restrict species' distributions.

PMID- 29346602
TI  - How Can We Best Protect Infants from Pertussis?

PMID- 29346603
TI  - Homologous stress adaptation, antibiotic resistance, and biofilm forming ability
      of Salmonella enterica serovar Heidelberg ATCC8326 on different food-contact
      surfaces following exposure to sublethal chlorine concentrations1.
AB  - Salmonella enterica serovar Heidelberg (American Type Culture Collection; ATCC
      8326) was examined for the ability to adapt to the homologous stress of chlorine
      through exposure to increasing chlorine concentrations (25 ppm daily increments)
      in tryptic soy broth (TSB). The tested strain exhibited an acquired tolerance to
      chlorine in TSB with the tolerant cells growing in concentrations up to 400 ppm.
      In addition, the chlorine stressed cells displayed rugose morphology on tryptic
      soy agar (TSA) plates at 37 degrees C. The minimum inhibitory concentration (MIC)
      of chlorine for adapted (rugose and smooth) cells was determined to be 550 ppm
      and 500 ppm, respectively whereas the MIC for the control was 450 ppm. The
      biofilm forming ability of the adapted and control cells were examined on both
      plastic and stainless steel surface at room temperature and 37 degrees C. The
      rugose variant, in contrast to the smooth (adapted and control) showed the
      ability to form strong biofilms (P <= 0.05) on a plastic surface at room
      temperature and 37 degrees C. Rugose cells compared to smooth and control
      attached more (P <= 0.05) to steel surfaces as well. The possibility of cross
      adaptation was examined by exposing the adapted and control cells to different
      antibiotics according to the Clinical & Laboratory Standards Institute
      guidelines. Adapted cells exhibited reduced susceptibility to some of the
      antibiotics tested as compared to control. The findings of this study suggest
      that exposure to sublethal chlorine concentration during the sanitization
      procedure can result in tolerant Salmonella cells. Chlorine may confer cross
      protection that aids in the survival of the tolerant population to other
      environmental stresses.

PMID- 29346604
TI  - Unique genetic profiles from cerebrospinal fluid cell-free DNA in leptomeningeal
      metastases of EGFR-mutant non-small-cell lung cancer: a new medium of liquid
      biopsy.
AB  - Background: Leptomeningeal metastases (LM) are more frequent in non-small-cell
      lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. Due
      to limited access to leptomeningeal lesions, the purpose of this study was to
      explore the potential role of cerebrospinal fluid (CSF) as a source of liquid
      biopsy in patients with LM. Patients and methods: Primary tumor, CSF, and plasma
      in NSCLC with LM were tested by next-generation sequencing. In total, 45 patients
      with suspected LM underwent lumbar puncture, and those with EGFR mutations
      diagnosed with LM were enrolled. Results: A total of 28 patients were enrolled in
      this cohort; CSF and plasma were available in 26 patients, respectively. Driver
      genes were detected in 100% (26/26), 84.6% (22/26), and 73.1% (19/26) of samples
      comprising CSF cell-free DNA (cfDNA), CSF precipitates, and plasma, respectively;
      92.3% (24/26) of patients had much higher allele fractions in CSF cfDNA than the
      other two media. Unique genetic profiles were captured in CSF cfDNA compared with
      those in plasma and primary tissue. Multiple copy number variations (CNVs) were
      mainly identified in CSF cfDNA, and MET copy number gain identified in 47.8%
      (11/23) of patients was the most frequent one, while other CNVs included ERBB2,
      KRAS, ALK, and MYC. Moreover, loss of heterozygosity (LOH) of TP53 was identified
      in 73.1% (19/26) CSF cfDNA, which was much higher than that in plasma (2/26,
      7.7%; P < 0.001). There was a trend towards a higher frequency of concomitant
      resistance mutations in patients with TP53 LOH than those without (70.6% versus
      33.3%; P = 0.162). EGFR T790M was identified in CSF cfDNA of 30.4% (7/23) of
      patients who experienced TKI progression. Conclusion: CSF cfDNA could reveal the
      unique genetic profiles of LM and should be considered as the most representative
      liquid biopsy medium for LM in EGFR-mutant NSCLC.

PMID- 29346605
TI  - The US Food and Drug Administration's use of regular approval for cancer drugs
      based on single-arm studies: implications for subsequent evidence generation.

PMID- 29346606
TI  - Characteristics of Cases With Repeated Sexually Transmitted Infections,
      Massachusetts, 2014-2016.
AB  - Background: Persons with prior sexually transmitted infections (STIs) are at high
      risk for reinfection. No recent studies have examined frequency with which
      persons are diagnosed and reported with multiple bacterial STIs over time.
      Methods: We conducted a retrospective, of confirmed syphilis, gonorrhea, and
      chlamydial infections reported to Massachusetts state surveillance system within
      a 2-year period, 28 July 2014-27 July 2016. Results: Among Massachusetts
      population aged 13-65 years (4847510), 49142 (1.0%) were reported with >=1 STIs;
      6999 (14.2% of those with >=1 STI) had >=2 STIs, accounting for 27.7% of STIs. Of
      cases with >=5 or more STIs (high-volume repeaters), 118 (74%) were men and 42
      (26%) were women. Men spanned the age spectrum and were predominantly non
      Hispanic white; 87% reported same-sex contacts. Women were younger, predominantly
      nonwhite, and without known same-sex contacts. Women were reinfected with
      gonorrhea and chlamydia or chlamydia alone; none had syphilis or human
      immunodeficiency virus (HIV) infection. All men with syphilis also had gonorrhea
      and/or chlamydia; 35% were diagnosed with HIV before, during, or within 10 months
      after study period. The majority (56%) of high-volume repeaters were seen at more
      than 1 care site/system. Conclusions: In Massachusetts, a large proportion of
      bacterial STIs are reported from a small subpopulation, many of whom have
      repeated infections and are likely to have higher impact on STI and HIV rates.
      Public health can play a crucial role in reaching high-volume repeaters whose STI
      histories may be hidden from clinicians due to fragmented care.

PMID- 29346607
TI  - Combined Endovascular and Microsurgical Treatment of a Premotor Arteriovenous
      Malformation: 2-Dimensional Operative Video.

PMID- 29346608
TI  - On-Demand Intraoperative 3-Dimensional Printing of Custom Cranioplastic
      Prostheses.
AB  - BACKGROUND: Currently, implantation of patient-specific cranial prostheses
      requires reoperation after a period for design and formulation by a third-party
      manufacturer. Recently, 3-dimensional (3D) printing via fused deposition modeling
      has demonstrated increased ease of use, rapid production time, and significantly
      reduced costs, enabling expanded potential for surgical application. Three
      dimensional printing may allow neurosurgeons to remove bone, perform a rapid
      intraoperative scan of the opening, and 3D print custom cranioplastic prostheses
      during the remainder of the procedure. OBJECTIVE: To evaluate the feasibility of
      using a commercially available 3D printer to develop and produce on-demand
      intraoperative patient-specific cranioplastic prostheses in real time and assess
      the associated costs, fabrication time, and technical difficulty. METHODS: Five
      different craniectomies were each fashioned on 3 cadaveric specimens (6 sides) to
      sample regions with varying topography, size, thickness, curvature, and
      complexity. Computed tomography-based cranioplastic implants were designed,
      formulated, and implanted. Accuracy of development and fabrication, as well as
      implantation ability and fit, integration with exiting fixation devices, and
      incorporation of integrated seamless fixation plates were qualitatively
      evaluated. RESULTS: All cranioprostheses were successfully designed and printed.
      Average time for design, from importation of scan data to initiation of printing,
      was 14.6 min and average print time for all cranioprostheses was 108.6 min.
      CONCLUSION: On-demand 3D printing of cranial prostheses is a simple, feasible,
      inexpensive, and rapid solution that may help improve cosmetic outcomes;
      significantly reduce production time and cost-expanding availability; eliminate
      the need for reoperation in select cases, reducing morbidity; and has the
      potential to decrease perioperative complications including infection and
      resorption.

PMID- 29346609
TI  - Decreased Serum Levels of Ghrelin and Brain-Derived Neurotrophic Factor in
      Premenopausal Women With Metabolic Syndrome.
AB  - Objective: We aimed to investigate the association between serum levels of
      ghrelin and brain-derived neurotrophic factor (BDNF) with MetS and its components
      in premenopausal women. Methods: 43 patients with MetS and 43 healthy controls
      participated in this study. Participants' body mass index (BMI), waist
      circumference (WC), systolic and diastolic blood pressure (SBP and DBP) were
      measured. Serum levels of total cholesterol (TC), triglyceride (TG), low and high
      density lipoprotein cholesterol (LDL-C and HDL-C), fasting blood sugar (FBS),
      insulin, BDNF and ghrelin determined. Homeostasis model assessment insulin
      resistance index (HOMA-IR) was also calculated. Results: Participants in MetS
      group had higher waist-to-hip ratios, elevated SBP and DBP, and higher serum
      levels of TG, FBS and insulin when compared with the control group. Serum ghrelin
      and BDNF levels were significantly lower in participants with MetS than in the
      healthier control subjects. There was a strong, positive correlation between
      serum ghrelin and BDNF levels. Both proteins negatively correlated with TG, FBS,
      HOMA-IR and positively with HDL-C. Furthermore, serum BDNF levels negatively
      associated with insulin levels. Conclusions: The findings indicate that
      variations occur in the circulating level of ghrelin and BDNF proteins in MetS
      patients. A strong correlation between serum ghrelin and BDNF suggests that
      production, release or practice of these 2 proteins might be related
      mechanically.

PMID- 29346610
TI  - Novel mutations in the lipase H gene lead to secretion defects of LIPH in Chinese
      patients with autosomal recessive woolly hair/hypotrichosis (ARWH/HT).
AB  - Autosomal recessive woolly hair/hypotrichosis (ARWH/HT: OMIM #278150/604379) is a
      rare hereditary hair disease characterized by tightly curled hair at birth which
      can lead to sparse hair later in life. The mutations in both LIPH and LPAR6/P2RY5
      are responsible for autosomal recessive woolly hair with or without hypotrichosis
      (ARWH/HT). To conduct clinical and genetic investigations in four patients from
      three unrelated Chinese Han families with ARWH/HT, we performed mutation
      screening of LIPH and LPAR6/P2RY5 gene and identified four mutations in LIPH:
      c.454G>A, c.614A>G, c.736T>A, c.742C>A. c.736T>A and c.742C>A mutations were
      reported in previous studies, and c.454G>A, c.614A>G were identified for the
      first time. We carried out functional studies of the two mutants with c.454G>A
      (p.Gly152Arg, G152R) or c.614A>G (p.His205Arg, H205R). Interestingly, both of
      them lead to secretion defects of LIPH, which are involved in the pathogenesis of
      ARWH/HT.

PMID- 29346612
TI  - Hyperpyrexia in a patient with a left ventricular assist device: a diagnosis
      beyond the obvious.
AB  - As the number of patients receiving a left ventricular assist device increases,
      physicians must always keep in mind that several conditions can present with non
      specific symptoms, such as fever, tachypnoea and confusion. We herein report the
      case of a left ventricular assist device patient who developed a life-threatening
      condition with acute hyperthermia, confusion and extremities' clonus and muscle
      spasms. The patient was diagnosed with serotonin syndrome, attributed to the
      coadministration of 2 commonly prescribed medications (citalopram and
      omeprazole). This case highlights that a significant proportion of left
      ventricular assist device patients is treated with serotonergic agents that may
      predispose them to the appearance of serotonin syndrome, a potentially life
      threatening condition.

PMID- 29346611
TI  - Combined roles of ATP and small hairpin RNA in the activation of RIG-I revealed
      by solution-based analysis.
AB  - RIG-I (retinoic acid inducible gene-I) is a cytosolic innate immune protein that
      senses viral dsRNA with a 5'-triphosphate overhang. Upon interaction with dsRNA a
      de-repression of the RIG-I CARD domains takes place that ultimately leads to the
      production of type I interferons and pro-inflammatory cytokines. Here we
      investigate the RIG-I conformational rearrangement upon interaction with an
      activating 5'-triphosphate-10-base pair dsRNA hairpin loop (10bp) compared with a
      less active 5'-triphosphate-8-base pair dsRNA hairpin loop (8bp). We use size
      exclusion chromatography-coupled small-angle X-ray scattering (SAXS) and limited
      tryptic digest experiments to show that that upon binding to 10 bp, but not 8 bp,
      RIG-I becomes extended and shows greater flexibility, reflecting the release of
      its CARDs. We also examined the effect of different ATP analogues on the
      conformational changes of RIG-I/dsRNA complexes. Of the analogues tested, the
      addition of ATP transition state analogue ADP-AlFx further assisted in the
      complete activation of RIG-I in complex with 10bp and also to some extent RIG-I
      bound to 8bp. Together these data provide solution-based evidence for the
      molecular mechanism of innate immune signaling by RIG-I as stimulated by short
      hairpin RNA and ATP.

PMID- 29346613
TI  - Review of chronic non-cancer pain research among Aboriginal people in Canada.
AB  - Purpose: Aboriginal people in Canada are disproportionately affected by chronic
      illnesses, compared to non-Aboriginal Canadians. The purpose of this review was
      to determine whether differences exist between the two groups with respect to
      chronic non-cancer pain (CNCP) in order to better inform clinical practice and to
      identify research gaps. Data sources: Four electronic databases were searched for
      the period of 1990-2015. Study selection: Only English and French language
      original studies that examined CNCP prevalence, assessment tools and beliefs
      among Aboriginal people in Canada were considered. Data extraction: Data
      extracted included Aboriginal group, geographic location, study setting and pain
      definition (for prevalence studies only). Results of data synthesis: A total of
      11 studies matched the selection criteria: 10 reported estimates of chronic pain
      prevalence among Aboriginal people in Canada, 1 was about a culturally adapted
      pain assessment tool, and no study was found about CNCP beliefs within Aboriginal
      people. Conclusion: CNCP among Aboriginal people is still a largely unexplored
      research field. The limited evidence available so far does not allow us to
      conclude that CNCP affects a higher proportion of Aboriginal than non-Aboriginal
      people in Canada. However, arthritis, a specific condition associated with
      chronic pain, is more prevalent in Aboriginal than non-Aboriginal people.
      Additional research is needed on other CNCP types and conditions. Furthermore,
      pain assessment tools are not culturally adapted and clinicians should inquire
      more about the beliefs of Aboriginal patients to make them feel safer and to
      better target interventions.

PMID- 29346614
TI  - Influenza Vaccine Effectiveness Against Influenza A(H3N2) Hospitalizations in
      Children in Hong Kong in a Prolonged Season, 2016/2017.
AB  - Background: Influenza A(H3N2) viruses circulated for 12 consecutive months in
      Hong Kong in 2016-2017, peaking in late June and July 2017. The objective of our
      study was to estimate the effectiveness of influenza vaccination in preventing
      hospitalizations in children in Hong Kong. Methods: We conducted a test-negative
      study between 1 September 2016 and 31 August 2017, enrolling children 6 months to
      17 years of age hospitalized for an acute respiratory infection. Influenza was
      diagnosed by PCR on nasopharyngeal aspirates. Results: We enrolled 5514 children,
      including 3608 children 6 months to 2 years, 1600 children 3-5 years, and 1206
      children 6-17 years of age. Influenza-associated hospitalizations occurred
      throughout the study year but time of vaccination of these children was also wide
      spread, from September 2016 to May 2017. Influenza vaccine effectiveness (VE) was
      39.7% (95% confidence interval [CI], 14.7%-57.3%) against laboratory-confirmed
      influenza A(H3N2). In analyses stratified by time since vaccination, the VE
      against influenza A(H3N2) was 52.8% (95% CI, 17.1%-73.2%) within 3 months of
      vaccination, and 31.2% (95% CI, -6.6% to 55.6%) 4-6 months after vaccination.
      Conclusions: Influenza vaccination was effective in preventing hospitalizations
      in children in Hong Kong.

PMID- 29346615
TI  - The RNA-splicing endonuclease from the euryarchaeaon Methanopyrus kandleri is a
      heterotetramer with constrained substrate specificity.
AB  - Four different types (alpha4, alpha'2, (alphabeta)2 and epsilon2) of RNA-splicing
      endonucleases (EndAs) for RNA processing are known to exist in the Archaea. Only
      the (alphabeta)2 and epsilon2 types can cleave non-canonical introns in precursor
      (pre)-tRNA. Both enzyme types possess an insert associated with a specific loop,
      allowing broad substrate specificity in the catalytic alpha units. Here, the
      hyperthermophilic euryarchaeon Methanopyrus kandleri (MKA) was predicted to
      harbor an (alphabeta)2-type EndA lacking the specific loop. To characterize MKA
      EndA enzymatic activity, we constructed a fusion protein derived from MKA alpha
      and beta subunits (fMKA EndA). In vitro assessment demonstrated complete removal
      of the canonical bulge-helix-bulge (BHB) intron structure from MKA pre-tRNAAsn.
      However, removal of the relaxed BHB structure in MKA pre-tRNAGlu was inefficient
      compared to crenarchaeal (alphabeta)2 EndA, and the ability to process the
      relaxed intron within mini-helix RNA was not detected. fMKA EndA X-ray structure
      revealed a shape similar to that of other EndA types, with no specific loop.
      Mapping of EndA types and their specific loops and the tRNA gene diversity among
      various Archaea suggest that MKA EndA is evolutionarily related to other
      (alphabeta)2-type EndAs found in the Thaumarchaeota, Crenarchaeota and
      Aigarchaeota but uniquely represents constrained substrate specificity.

PMID- 29346616
TI  - Racial differences in family health history knowledge of type 2 diabetes:
      exploring the role of interpersonal mechanisms.
AB  - Collecting complete and accurate family health history is critical to preventing
      type 2 diabetes. Whether there are any racial difference in family health history
      knowledge of type 2 diabetes and whether such differences are related to
      interpersonal mechanisms remain unclear. We seek to identify the interpersonal
      mechanisms that give rise to discrepancies in family health history knowledge of
      type 2 diabetes in families of different racial backgrounds. We analyze informant
      dyad consensus with respect to shared family history of type 2 diabetes in 127
      informants of 45 families in the greater Cincinnati area (white: 28 families, 78
      informants; black/African-American: 17 families, 49 informants). We first
      document a difference in informant-dyad consensus by race and then test whether
      this difference can be explained by interpersonal ties, particularly health
      communication. Compared with their white counterparts, dyads in families of
      black/African-American background are more likely to have an uneven distribution
      of knowledge, with one informant knowing and the other not knowing his/her family
      health history. The racial difference is explained by dyads in families of
      black/African-American background having fewer reciprocal health communication
      ties. While associated with informant-dyad consensus, education, kinship ties,
      and closeness ties do not account for the observed racial difference. Activating
      health communication is a key to improving family health history knowledge,
      especially in families of black/African-American background. Researchers and
      clinicians should leverage communication ties in the family network for better
      collection and utilization of family health history in preventive services.

PMID- 29346617
TI  - Riboswitching with ciprofloxacin-development and characterization of a novel RNA
      regulator.
AB  - RNA molecules play important and diverse regulatory roles in the cell. Inspired
      by this natural versatility, RNA devices are increasingly important for many
      synthetic biology applications, e.g. optimizing engineered metabolic pathways,
      gene therapeutics or building up complex logical units. A major advantage of RNA
      is the possibility of de novo design of RNA-based sensing domains via an in vitro
      selection process (SELEX). Here, we describe development of a novel ciprofloxacin
      responsive riboswitch by in vitro selection and next-generation sequencing-guided
      cellular screening. The riboswitch recognizes the small molecule drug
      ciprofloxacin with a KD in the low nanomolar range and adopts a pseudoknot fold
      stabilized by ligand binding. It efficiently interferes with gene expression both
      in lower and higher eukaryotes. By controlling an auxotrophy marker and a
      resistance gene, respectively, we demonstrate efficient, scalable and
      programmable control of cellular survival in yeast. The applied strategy for the
      development of the ciprofloxacin riboswitch is easily transferrable to any small
      molecule target of choice and will thus broaden the spectrum of RNA regulators
      considerably.

PMID- 29346619
TI  - Spurious Thrombocytopenia in Automated Platelet Count.
AB  - Spurious thrombocytopenia is a well-known phenomenon observed with the widespread
      use of hematology analyzers (HAs). In this study, 355 specimens with pseudo
      thrombocytopenia (PTCP) were evaluated via epidemiology, identification,
      remedies, and platelet (PLT) count. Data showed that anticoagulants such as
      citrate and/or heparin-dependent PTCP (16.0%) became increasingly common, whereas
      ethylenediaminetetraacetic acid (EDTA)-induced PTCP (49.1%) remained the most
      frequent. We note that that nearly half of the patients with PTCP had veritable
      decreased PLT counts, even after PLT levels had been corrected. Our findings
      suggest that there were seasonal changes in patients with PTCP: PLT levels were
      higher in spring, compared with other seasons, with winter levels being the
      lowest. There were higher risks of PTCP for individuals with malignant neoplasms,
      liver diseases, infection, and hematologic disease, compared with other
      conditions. PTCP is related to diseases, rather than being a simple phenomenon,
      and thus demands careful attention.

PMID- 29346618
TI  - Evidence of Adaptive Evolution and Relaxed Constraints in Sex-Biased Genes of
      South American and West Indies Fruit Flies (Diptera: Tephritidae).
AB  - Several studies have demonstrated that genes differentially expressed between
      sexes (sex-biased genes) tend to evolve faster than unbiased genes, particularly
      in males. The reason for this accelerated evolution is not clear, but several
      explanations have involved adaptive and nonadaptive mechanisms. Furthermore, the
      differences of sex-biased expression patterns of closely related species are also
      little explored out of Drosophila. To address the evolutionary processes involved
      with sex-biased expression in species with incipient differentiation, we analyzed
      male and female transcriptomes of Anastrepha fraterculus and Anastrepha obliqua,
      a pair of species that have diverged recently, likely in the presence of gene
      flow. Using these data, we inferred differentiation indexes and evolutionary
      rates and tested for signals of selection in thousands of genes expressed in head
      and reproductive transcriptomes from both species. Our results indicate that sex
      biased and reproductive-biased genes evolve faster than unbiased genes in both
      species, which is due to both adaptive pressure and relaxed constraints.
      Furthermore, among male-biased genes evolving under positive selection, we
      identified some related to sexual functions such as courtship behavior and
      fertility. These findings suggest that sex-biased genes may have played important
      roles in the establishment of reproductive isolation between these species, due
      to a combination of selection and drift, and unveil a plethora of genetic markers
      useful for more studies in these species and their differentiation.

PMID- 29346620
TI  - Combating Global Antibiotic Resistance: Emerging One Health Concerns in Lower-
      and Middle-Income Countries.
AB  - Antibiotic misuse in lower- and middle-income countries (LMICs) contributes to
      the development of antibiotic resistance that can disseminate globally.
      Strategies specific to LMICs that seek to reduce antibiotic misuse by humans, but
      simultaneously improve antibiotic access, have been proposed. However, most
      approaches to date have not considered the growing impact of animal and
      environmental reservoirs of antibiotic resistance, which threaten to exacerbate
      the antibiotic resistance crisis in LMICs. In particular, current strategies do
      not prioritize the impacts of increased antibiotic use for terrestrial food
      animal and aquaculture production, inadequate food safety, and widespread
      environmental pollution. Here, we propose new approaches that address emerging,
      One Health challenges.

PMID- 29346621
TI  - Assessing polymyalgia rheumatica activity when C-reactive protein is unavailable
      or uninterpretable.
AB  - Objective: The PMR activity score (PMR-AS) includes the CRP value, which may be
      lacking or invalid owing to anti-IL-6 therapy. Our objective was to develop
      alternatives to PMR-AS that do not require CRP. Methods: We used the Club
      Rhumatisme et Inflammation (CRI; 89 patients with PMR) and the Tolerance and
      Efficacy of tocilizumab iN pOlymyalgia Rheumatica (TENOR; 20 patients with recent
      onset PMR naive to glucocorticoid who received three tocilizumab infusions, at
      weeks 0, 4 and 8, followed by prednisone from weeks 12 to 24) cohorts. In the CRI
      cohort, we evaluated correlations between PMR-AS items to select the best item
      for imputing CRP. Then we calculated the PMR-AS with (PMR-AS) and without (clin
      PMR-AS) CRP and we used the linear regression between PMR-AS and clin-PMR-AS to
      obtain CRP-imputed (CRP-imp) PMR-AS. Finally, we evaluated agreement between clin
      PMR-AS, CRP-imp PMR-AS, PMR-AS and ESR-PMR-AS in the TENOR cohort during
      tocilizumab therapy. Results: In the CRI cohort, agreement between PMR-AS and
      clin-PMR-AS was excellent (kappa = 0.90). Linear regression between PMR-AS and
      clin-PMR-AS [CRP-imp PMR-AS = 1.12(clin-PMR-AS)+0.26] allowed us to build the CRP
      imp PMR-AS. Mean (s.d.) values were as follows: 8.40 (9.76) for PMR-AS, 7.24
      (8.58) for clin-PMR-AS and 7.84 (9.61) for CRP-imp PMR-AS. CRP-imp PMR-AS agreed
      more closely with PMR-AS than did clin-PMR-AS. The results in the TENOR cohort
      confirmed that CRP-imp PMR-AS or ESR-PMR-AS could be used. Conclusion:
      Alternatives to the PMR-AS obtained without CRP can be used to monitor PMR
      activity in everyday practice in patients without available CRP values and in
      those receiving IL-6 antagonist therapy.

PMID- 29346622
TI  - A Nosocomial Foodborne Outbreak of a VIM Carbapenemase-Expressing Citrobacter
      freundii.
AB  - Background: A foodborne outbreak of VIM carbapenemase-expressing Citrobacter
      freundii (CPC) occurred between February 2016 and June 2016 at a major university
      hospital in Germany. Methods: An explosive increase in CPC isolated from rectal
      swabs of patients during weekly routine screening led to the declaration of an
      outbreak. A hospital-wide prevalence screening was initiated as well as screening
      of all patients on admission and before transfer to another ward, canteen staff,
      patient rooms, medical and kitchen inventory, and food. Swabs were streaked out
      on selective plates. All CPC isolates were analyzed using mass spectrometry, and
      selected isolates were analyzed using whole-genome sequencing. Results: A total
      of 76 were identified; most were unrelated cases in different wards. The CPC was
      isolated from retained samples of prepared vegetable salads and puddings and from
      a mixing machine used to prepare these foods only after an overnight culture. The
      immediate ban on serving potential source food resulted in a sharp decline and
      finally disappearance of novel cases. Repeated testing of presliced vegetables
      showed a high degree of contamination with C. freundii without a carbapenemase,
      indicating a possible source. Conclusions: An explosive increase in carbapenemase
      expressing Enterobacteriaceae contamination may have been caused by a foodborne
      source, and presliced vegetables should be taken into account as a putative
      pathogen repository. These findings underline the importance of appropriate
      cooling, transport, reheating, and distribution of meals and indicate that
      probing of nonorganic surfaces is limited by low sensitivity, which may be
      increased by additional overnight cultivation in appropriate media.

PMID- 29346623
TI  - A large-scale field study of bacterial communities in cereal aphid populations
      across Morocco.
AB  - Insects are frequently associated with bacteria that can have significant
      ecological and evolutionary impacts on their hosts. To date, few studies have
      examined the influence of environmental factors to microbiome composition of
      aphids. The current work assessed the diversity of bacterial communities of five
      cereal aphid species (Sitobion avenae, Rhopalosiphum padi, R. maidis, Sipha
      maydis and Diuraphis noxia) collected across Morocco, covering a wide range of
      environmental conditions. We aimed to test whether symbiont combinations are host
      or environment specific. Deep 16S rRNA sequencing enabled us to identify 17
      bacterial operational taxonomic units (OTUs). The obligate symbiont Buchnera
      aphidicola was represented by five OTUs with multiple haplotypes in many single
      samples. Facultative endosymbionts were presented by a high prevalence of
      Regiella insecticola and Serratia symbiotica in S. avenae and Si. maydis,
      respectively. In addition to these symbiotic partners, Pseudomonas,
      Acinetobacter, Pantoea, Erwinia and Staphyloccocus were also identified in
      aphids, suggesting that the aphid microbiome is not limited to the presence of
      endosymbiotic bacteria. Beside a significant association between host species and
      bacterial communities, an inverse correlation was also found between altitude and
      alpha-diversity. Overall, our results support that symbiont combinations are
      mainly host specific.

PMID- 29346624
TI  - Data-driven approaches to define the upper limit of the intermovement interval of
      periodic leg movements during sleep.
AB  - Study Objectives: To define statistically the upper limit of the intermovement
      interval (IMI, the time interval between the onset of consecutive movements) of
      periodic leg movements during sleep (PLMS). Methods: We computed the IMI
      distribution of a large sample (n = 141) of patients with restless legs syndrome
      (RLS) and analyzed it with two independent approaches, based on fitting either
      empirical functions or normal and exponential functions to the data. Results: The
      two fitting approaches consistently pointed to an upper limit of the PLMS IMI in
      the range between 50 and 60 s. Decreasing the upper limit of PLMS IMI from 90 to
      60 s evidently decreased the PLMS index in patients with RLS and control
      participants; nevertheless, the PLMS index remained significantly higher in RLS
      vs. control participants. Shifting the upper limit of PLMS IMI to 60 s did not
      significantly modify the effectiveness of discrimination of PLMS between controls
      and patients with RLS. Conclusion: These results seem to indicate that a
      conservative, yet data-driven upper limit for IMI contributing to the PLMS in
      patients with RLS might be 60 s instead of 90 s, as recommended by the present
      guidelines.

PMID- 29346626
TI  - Anti-aminoacyl tRNA synthetase antibody-positive clinically amyopathic
      dermatomyositis.

PMID- 29346625
TI  - Complete genomic and transcriptional landscape analysis using third-generation
      sequencing: a case study of Saccharomyces cerevisiae CEN.PK113-7D.
AB  - Completion of eukaryal genomes can be difficult task with the highly repetitive
      sequences along the chromosomes and short read lengths of second-generation
      sequencing. Saccharomyces cerevisiae strain CEN.PK113-7D, widely used as a model
      organism and a cell factory, was selected for this study to demonstrate the
      superior capability of very long sequence reads for de novo genome assembly. We
      generated long reads using two common third-generation sequencing technologies
      (Oxford Nanopore Technology (ONT) and Pacific Biosciences (PacBio)) and used
      short reads obtained using Illumina sequencing for error correction. Assembly of
      the reads derived from all three technologies resulted in complete sequences for
      all 16 yeast chromosomes, as well as the mitochondrial chromosome, in one step.
      Further, we identified three types of DNA methylation (5mC, 4mC and 6mA).
      Comparison between the reference strain S288C and strain CEN.PK113-7D identified
      chromosomal rearrangements against a background of similar gene content between
      the two strains. We identified full-length transcripts through ONT direct RNA
      sequencing technology. This allows for the identification of transcriptional
      landscapes, including untranslated regions (UTRs) (5' UTR and 3' UTR) as well as
      differential gene expression quantification. About 91% of the predicted
      transcripts could be consistently detected across biological replicates grown
      either on glucose or ethanol. Direct RNA sequencing identified many
      polyadenylated non-coding RNAs, rRNAs, telomere-RNA, long non-coding RNA and
      antisense RNA. This work demonstrates a strategy to obtain complete genome
      sequences and transcriptional landscapes that can be applied to other eukaryal
      organisms.

PMID- 29346629
TI  - HIV-1 Control and Immunoglobulin Genes.

PMID- 29346627
TI  - Severe and protracted sleep disruptions in mouse model of post-traumatic stress
      disorder.
AB  - Increasing evidences suggest that the predator threat model is a valid animal
      model of post-traumatic stress disorder (PTSD). However, sleep has never been
      examined in this model. Since sleep disturbances, including insomnia and
      excessive daytime sleepiness, are severe and protracted symptoms of PTSD, we
      hypothesized that mice exposed to predator odor trauma (POT) will display
      contextual fear conditioning along with severe and protracted sleep disruptions.
      Adult male C57BL/6J mice, instrumented with wire electrodes (to record
      hippocampal local field potentials [LFP] and nuchal muscle [electromyogram, EMG]
      activity), were exposed to contextual conditioning using soiled cat litter as
      unconditional stimulus (US). On day 1, fear memory acquisition (FMA) training was
      performed by exposing mice to contextual cage (conditional stimulus; CS) for 30
      min followed by exposure to CS + US for 90 min. On day 5, fear memory recall
      (FMR) testing was performed by exposing mice to CS (without US) for 120 min. LFP
      and EMG were recorded continuously for 5 days. Mice exposed to POT displayed as
      follows: (1) hyperarousal coupled with electrophysiological indicators of memory
      acquisition and retrieval (increased hippocampal theta and gamma power) during
      FMA and FMR; (2) increased nonrapid eye movement (NREM) delta and rapid eye
      movement theta power during sleep post FMA, indicating memory consolidation; (3)
      protracted sleep disturbances as evident by increased wakefulness, reduced NREM
      sleep and NREM delta power, increased NREM beta power during light (sleep)
      period, and increased sleep during dark (active) period. Based on these results,
      we suggest that mice exposed to POT display severe and protracted sleep
      disturbances mimicking sleep disturbance observed in human PTSD.

PMID- 29346630
TI  - Vitamin D Toxicity: A 16-Year Retrospective Study at an Academic Medical Center.
AB  - Background: Interest in vitamin D has increased during the past 2 decades, with a
      corresponding increase in laboratory testing of 25-hydroxyvitamin D [25(OH)D].
      The vast majority of specimens tested display normal or deficient levels of
      25(OH)D; concentrations rarely fall in the potentially toxic range. Methods: We
      performed a retrospective investigation of elevated 25(OH)D levels during a 16
      year period at the University of Iowa Hospitals and Clinics (UIHC), a 734-bed
      tertiary-/quaternary-care academic medical center in the midwestern United
      States. Detailed medical-record review was performed for patients with
      serum/plasma 25(OH)D concentrations higher than 120 ng per mL. Results: A total
      of 127,932 serum/plasma 25(OH)D measurements were performed on 73,779 unique
      patients. Of these patients, 780 (1.05%) had results that exceeded 80 ng per mL
      and 89 patients (0.12%) had results that exceeded 120 ng per mL. Only 4 patients
      showed symptoms of vitamin D toxicity. Three of these cases involved inadvertent
      misdosing of liquid formulations. Conclusions: Symptomatic vitamin D toxicity is
      uncommon, and elevated levels of 25(OH)D do not strongly correlate with clinical
      symptoms or total serum/plasma calcium levels. Our study highlights the potential
      risks of the liquid formulation of vitamin D.

PMID- 29346631
TI  - Anticardiolipin antibodies and 12-month graft function in kidney transplant
      recipients: a prognosis cohort survey.
AB  - Background: In kidney transplant recipients, anticardiolipin (ACL) antibodies
      without antiphospholipid syndrome (APS) are found in up to 38% of patients and
      could be associated with thrombotic events (TEs). However, the prognostic role of
      ACL regarding kidney transplant and patients outcomes have still not been well
      defined. Methods: We conducted an observational, monocentric, retrospective
      cohort study including 446 kidney transplant recipients and standardized follow
      up: 36-month allograft and patient survival, 12-month estimated glomerular
      filtration rate (eGFR) and 3- and 12-month screening biopsies. Results: ACL tests
      were run on 247 patients, 101 were positive (ACL+ group, 41%) and 146 were
      negative (ACL- group, 59%). Allografts and patient survival within 36 months as
      TE were similar between both groups [hazard ratio (HR) = 1.18 and HR = 0.98,
      respectively]. The 12-month eGFR was significantly lower in the ACL+ group
      [median (95% confidence interval) 48.5 (35.1-60.3) versus 51.9 (39.1-65.0)
      mL/min/1.73 m2, P= 0.042]. ACL+ was independently associated with eGFR decrease
      (P = 0.04). In 12-month screening biopsies, tubular atrophy was significantly
      more severe in the ACL+ group compared with the ACL- group (P = 0.02).
      Conclusions: ACL without APS before kidney transplantation is an independent risk
      factor of eGFR decline within the first year post-transplant without over
      incidence of TEs. Specific immunosuppressive therapy including mammalian target
      of rapamycin inhibitors should be discussed in the future.

PMID- 29346632
TI  - Diagnostic and Prognostic Value of JC Virus DNA in Plasma in Progressive
      Multifocal Leukoencephalopathy.
AB  - Background: Progressive multifocal leukoencephalopathy (PML) is a severe
      demyelinating disease caused by the polyomavirus JC (John Cunningham; JCV) that
      affects patients with impaired immune systems. While JCV-DNA detection in
      cerebrospinal fluid (CSF) is diagnostic of PML, the clinical significance of
      plasma JCV-DNA is uncertain. Methods: We retrospectively analyzed plasma samples
      from PML patients that were drawn close to disease onset and from controls
      without PML. In PML patients, we compared plasma JCV-DNA detection and levels to
      clinical and laboratory parameters, and patient survival. Results: JCV-DNA was
      detected in plasma of 49/103 (48%) patients with PML (20/24, 83%, human
      immunodeficiency virus [HIV] negative; 29/79, 37%, HIV-positive) and of 4/144
      (3%) controls without PML (0/95 HIV-negative; 4/49, 8%, HIV-positive), yielding a
      diagnostic sensitivity and specificity of 48% and 97% (83% and 100% in HIV
      negative; 37% and 92% in HIV-positive), respectively. Among 16 PML patients with
      undetectable CSF JCV-DNA, 4 (25%) had detectable plasma JCV-DNA. Plasma JCV-DNA
      levels were independently associated with CSF levels (P < .0001) and previous
      corticosteroid treatment (P = .012). Higher plasma JCV-DNA levels were associated
      with disease progression in HIV-negative patients (P = .005); in HIV-positive
      patients, there was an increased risk of progression only in those treated with
      combination antiretroviral therapy (cART; P < .0001). Conclusions: Testing JCV
      DNA in plasma might complement PML diagnosis, especially when CSF is unavailable
      or JCV-DNA not detectable in CSF. In addition, JCV-DNA plasma levels could be
      useful as a marker of disease progression in both HIV-negative and cART-treated,
      HIV-positive PML patients.

PMID- 29346633
TI  - Intraoperative epicardial focal pulmonary venous electrocardiography in patients
      with atrial fibrillation.
AB  - OBJECTIVES: In patients referred to off-pump coronary artery bypass grafting,
      pulmonary vein isolation (PVI) may be used for those with persistent atrial
      fibrillation (AF), an alternative to the Maze procedure. However, the success
      rate of PVI in persistent AF is limited. The study assesses the prognostic value
      of focal epicardial electrocardiography of the pulmonary veins (PVs) for surgical
      ablation results. METHODS: We mapped 140 PV in 35 cases undergoing off-pump
      coronary artery bypass grafting. Data obtained using a sensing-pacing probe
      before ablation were analysed. The composite study end-point consisted of the
      need for electrical cardioversion for in-hospital recurrence of AF and the
      presence of AF at hospital discharge and after 6 months follow-up confirmed by 24
      h Holter electrocardiographic monitoring. RESULTS: In patients with epicardial
      far-field (FF) signals recorded over at least 1 PV, the composite end-point
      occurred in 61% (14) vs 25% (3) of patients with no FF signal recorded over any
      PV (P = 0.04). The presence of FF signals in at least 1 PV significantly
      increased the risk of composite end-point occurrence (odds ratio 3; P = 0.04).
      The composite end-point occurred in 86% (6) of patients with FF signals recorded
      over all PVs and in 39% (11) in the remainder of the study population (P = 0.03).
      CONCLUSIONS: Intraoperative epicardial focal electrocardiography of PVs revealed
      more than 40% of PVs had only FF atrial signals. The presence of FF signals in
      PVs is related to a lower early effectiveness of PVI on ablating AF. Epicardial
      focal electrocardiography of PVs may be a clinically effective intraoperative
      tool in the decision-making process between less invasive PVI and the standard
      Maze procedure.

PMID- 29346634
TI  - Are people getting quality thalassemia care in twin cities of Pakistan? A
      comparison with international standards.
AB  - Objectives: This study was conducted to determine if thalassemia patients were
      getting quality care in Rawalpindi and Islamabad, Pakistan, as per international
      standards and to identify determinants for better quality of thalassemia care.
      Design: A cross sectional study was conducted using interview based structured
      questionnaire, which was developed using standards of thalassemia care used by
      International Thalassemia Foundation. Setting: Five healthcare facilities
      catering to the needs of thalassemia patients in Rawalpindi and Islamabad,
      Pakistan. Participants: Data were collected from 315 thalassemia patients from
      May to August, 2016. Main outcome measure: Survey data on quality indicators.
      Results: Results showed that almost half of thalassemia patients (48.5%) were
      getting poor quality of care. On average patients were getting only 63.93% of
      possible quality care for the disease. The most deficient quality area was
      management of complications where patients were getting only 49.1% of possible
      care. Better quality of care was likely to be received by those patients who were
      educated, patients with educated fathers, those visiting private facilities and
      those who were visiting facilities in Islamabad. Those with concomitant diseases
      were also likely to receive better care. Conclusion: Quality of care provided to
      thalassemia patients was well below the international standards for the care of
      thalassemia. There is a need to take urgent action to improve quality of care in
      the country.

PMID- 29346635
TI  - A scoping study of frameworks for adapting public health evidence-based
      interventions.
AB  - Evidence-based public health translation of research to practice is essential to
      improve the public's health. Dissemination and implementation researchers have
      explored what happens once practitioners adopt evidence-based interventions
      (EBIs) and have developed models and frameworks to describe the adaptation
      process. This scoping study identified and summarized adaptation frameworks in
      published reports and grey literature. We followed the recommended steps of a
      scoping study: (a) identifying the research question; (b) identifying relevant
      studies; (c) selecting studies; (d) charting the data; (e) collating,
      summarizing, and reporting the results; and (f) consulting with experts. We
      searched PubMed, PsycINFO, PsycNET, and CINAHL databases for articles referencing
      adaptation frameworks for public health interventions in the published and gray
      literature, and from reference lists of framework articles. Two reviewers
      independently coded the frameworks and their steps and identified common steps.
      We found 13 adaptation frameworks with 11 program adaptation steps: (a) assess
      community, (b) understand the EBI(s), (c) select the EBI, (d) consult with
      experts, (e) consult with stakeholders, (f) decide on needed adaptations, (g)
      adapt the original EBI, (h) train staff, (i) test the adapted materials, (j)
      implement the adapted EBI, and (k) evaluate. Eight of these steps were
      recommended by more than five frameworks: #1-3, 6-7, and 9-11. This study is the
      first to systematically identify, review, describe, and summarize frameworks for
      adapting EBIs. It contributes to the literature by consolidating key steps in
      program adaptation of EBIs and describing the associated tasks in each step.

PMID- 29346636
TI  - Tuberculosis among the homeless in Chennai city, South India.
AB  - Background: In India from a national perspective, the incidence/prevalence of
      active tuberculosis (TB) among the homeless are unknown. Methods: Homeless
      individuals, aged 15 years and above, were screened for TB by radiography and
      smear examination in Chennai city. Results: 301 individuals were enrolled and
      screened for TB; 8% (24/301) had chest symptoms; 5.6% (17/301) found X-ray
      abnormalities. The overall prevalence of TB was 1661/100 000; prevalence of
      culture-positive TB was 997/100 000 and smear-positive TB was 664/100 000
      population. Conclusion: There is a need to address TB control among homeless
      populations. The current pilot study showed that the prevalence of TB was
      disproportionately high and there is a need for a larger study with an adequately
      powered sample size.

PMID- 29346637
TI  - Scleroderma renal crisis and cancer.

PMID- 29346638
TI  - Standardized languages and notations for graphical modelling of patient care
      processes: a systematic review.
AB  - Purpose: The importance of working toward quality improvement in healthcare
      implies an increasing interest in analysing, understanding and optimizing process
      logic and sequences of activities embedded in healthcare processes. Their
      graphical representation promotes faster learning, higher retention and better
      compliance. The study identifies standardized graphical languages and notations
      applied to patient care processes and investigates their usefulness in the
      healthcare setting. Data sources: Peer-reviewed literature up to 19 May 2016.
      Information complemented by a questionnaire sent to the authors of selected
      studies. Study selection: Systematic review conducted in accordance with the
      Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement.
      Data extraction: Five authors extracted results of selected studies. Results of
      data synthesis: Ten articles met the inclusion criteria. One notation and
      language for healthcare process modelling were identified with an application to
      patient care processes: Business Process Model and Notation and Unified Modeling
      LanguageTM. One of the authors of every selected study completed the
      questionnaire. Users' comprehensibility and facilitation of inter-professional
      analysis of processes have been recognized, in the filled in questionnaires, as
      major strengths for process modelling in healthcare. Conclusion: Both the
      notation and the language could increase the clarity of presentation thanks to
      their visual properties, the capacity of easily managing macro and micro
      scenarios, the possibility of clearly and precisely representing the process
      logic. Both could increase guidelines/pathways applicability by representing
      complex scenarios through charts and algorithms hence contributing to reduce
      unjustified practice variations which negatively impact on quality of care and
      patient safety.

PMID- 29346639
TI  - Comparison of Dopamine D3 and D2 Receptor Occupancies by a Single Dose of
      Blonanserin in Healthy Subjects: A Positron Emission Tomography Study With [11C]
      (+)-PHNO.
AB  - Background: Blockade of D3 receptor, a member of the dopamine D2-like receptor
      family, has been suggested as a possible medication for schizophrenia.
      Blonanserin has high affinity in vitro for D3 as well as D2 receptors. We
      investigated whether a single dose of 12 mg blonanserin, which was within the
      daily clinical dose range (i.e., 8-24 mg) for the treatment of schizophrenia,
      occupies D3 as well as D2 receptors in healthy subjects. Methods: Six healthy
      males (mean 35.7+/-7.6 years) received 2 positron emission tomography scans, the
      first prior to taking blonanserin, and the second 2 hours after the
      administration of a single dose of 12 mg blonanserin. Dopamine receptor
      occupancies by blonanserin were evaluated by [11C]-(+)-PHNO. Results: Occupancy
      of each region by 12 mg blonanserin was: caudate (range 64.3%-81.5%; mean+/-SD,
      74.3+/-5.6%), putamen (range 60.4%-84.3%; mean+/-SD, 73.3%+/-8.2%), ventral
      striatum (range 40.1%-88.2%; mean+/-SD, 60.8%+/-17.1%), globus pallidus (range
      65.8%-87.6%; mean+/-SD, 75.7%+/-8.6%), and substantia nigra (range 56.0%-88.7%;
      mean+/-SD, 72.4%+/-11.0%). Correlation analysis between plasma concentration of
      blonanserin and receptor occupancy in D2-rich (caudate and putamen) and D3-rich
      (globus pallidus and substantia nigra) regions showed that EC50 for D2-rich
      region was 0.39 ng/mL (r=0.43) and EC50 for D3-rich region was 0.40 ng/mL
      (r=0.79). Conclusions: A single dose of 12 mg blonanserin occupied D3 receptor to
      the same degree as D2 receptor in vivo. Our results were consistent with previous
      studies that reported that some of the pharmacological effect of blonanserin is
      mediated via D3 receptor antagonism.

PMID- 29346640
TI  - Preventive chemotherapy to control soil-transmitted helminthiasis averted more
      than 500 000 DALYs in 2015.
AB  - Background: Preventive chemotherapy (PC), the large-scale administration of
      anthelminthics, is recommended by the World Health Organization (WHO) for the
      control of soil-transmitted helminthiasis (STH). Since 2010, donated
      anthelminthics for STH have boosted the implementation of PC programmes in
      children, achieving global coverage of more than 60% in 2015. The WHO Global
      Health Estimates attribute an annual loss of over 3.3 million disability-adjusted
      life-years (DALYs) to STH. The aim of this study is to estimate the impact of PC
      programmes on child morbidity. Method: We used data from the WHO Global Health
      Estimates, national coverage data on PC and the results of an evaluation of the
      impact of PC in 17 countries on morbidity previously conducted by our group.
      Results: We estimated that the implementation of PC averted in 2015 over 44% of
      the DALYs that would have been caused in children by STH without the control
      intervention. A reduction in morbidity of over 75% is expected, if the global
      target is reached in 2020. If the programme is subsequently maintained, morbidity
      from STH will be almost totally removed by 2025. Conclusions: In endemic areas,
      preventive chemotherapy provides a significant health benefit. We consider this
      estimation potentially useful to evaluate the cost utility of the investment made
      by several endemic countries on PC to control STH.

PMID- 29346641
TI  - Uncovering behavioural diversity amongst high-strength Pseudomonas spp.
      surfactants at the limit of liquid surface tension reduction.
AB  - Bacterial biosurfactants have a wide range of biological functions and
      biotechnological applications. Previous analyses had suggested a limit to their
      reduction of aqueous liquid surface tensions (gammaMin), and here we confirm this
      in an analysis of 25 Pseudomonas spp. strains isolated from soil which produce
      high-strength surfactants that reduce surface tensions to 25.2 +/- 0.1-26.5 +/-
      0.2 mN m-1 (the surface tension of sterile growth medium and pure water was 52.9
      +/- 0.4 mN m-1 and 72.1 +/- 1.2 mN m-1, respectively). Comparisons of culture
      supernatants produced using different growth media and semi-purified samples
      indicate that the limit of 24.2-24.7 mN m-1 is not greatly influenced by culture
      conditions, pH or NaCl concentrations. We have used foam, emulsion and oil
      displacement behavioural assays as a simple and cost-effective proxy for in-depth
      biochemical characterisation, and these suggest that there is significant
      structural diversity amongst these surfactants that may reflect different
      biological functions and offer new biotechnological opportunities. Finally, we
      obtained a draft genome for the strain producing the highest strength surfactant,
      and identified a cluster of non-ribosomal protein synthase genes that may produce
      a cyclic lipopeptide (CLP)-like surfactant. Further investigation of this group
      of related bacteria recovered from the same site will allow a better
      understanding of the significance of the great variety of surfactants produced by
      bacterial communities found in soil and elsewhere.

PMID- 29346642
TI  - RNase 7 but not psoriasin nor sPLA2-IIA associates with Mycobacterium
      tuberculosis during airway epithelial cell infection.
AB  - Tuberculosis is a disease caused by Mycobacterium tuberculosis (Mtb). Innate
      immunity is the first line of defense against Mtb and malfunctions in any of its
      components are associated with the susceptibility to the disease. Epithelial
      products such as host defense peptides (HDPs) are the first molecules produced to
      counteract the infection. Although a wide variety of HDPs are produced by
      epithelial cells only a few of them have been studied during Mtb infection. Here,
      we assessed the expression and production of the HDPs psoriasin, secreted
      phospholipases A2 (sPLA2-IIA) and Ribonuclease (RNase) 7 in airway epithelial
      cells (NCI-H292), type II pneumocytes (A549 cells) and monocyte-derived
      macrophages from human peripheral blood mononuclear cells and from the human cell
      line THP1 after Mtb in vitro infection. Results show that psoriasin and sPLA2-IIA
      were not induced by Mtb in any of the evaluated cells, while RNase 7 was
      overexpressed in infected airway epithelial cells. Intracellular analysis by flow
      cytometry demonstrated that the highest levels of RNase 7 were observed 6 h post
      infection and the induction was dependent on direct interaction between airway
      epithelial cells and Mtb. In addition, analysis by electron microscopy showed
      that RNase 7 was capable of attaching to the cell wall of intracellular
      mycobacteria. Our studies suggest that the induction of RNase 7 in response to
      Mtb could have a role in anti-mycobacterial immunity, which needs to be studied
      as an innate immune mechanism.

PMID- 29346643
TI  - Genetic characterization of a VanG-type vancomycin-resistant Enterococcus faecium
      clinical isolate.
AB  - Objectives: To characterize, phenotypically and genotypically, the first
      Enterococcus faecium clinical isolate harbouring a vanG operon. Methods: The
      antibiotic resistance profile of E. faecium 16-346 was determined and its whole
      genome sequenced using PacBio technology. Attempts to transfer vancomycin
      resistance by filter mating were performed and the inducibility of expression of
      the vanG operon was studied by reverse-transcription quantitative PCR (RT-qPCR)
      in the presence or absence of subinhibitory concentrations of vancomycin.
      Results: E. faecium 16-346 was resistant to rifampicin (MIC >4 mg/L),
      erythromycin (MIC >4 mg/L), tetracycline (MIC >16 mg/L) and vancomycin (MIC 8
      mg/L), but susceptible to teicoplanin (MIC 0.5 mg/L). The strain harboured the
      vanG operon in its chromosome, integrated in a 45.5 kb putative mobile genetic
      element, similar to that of Enterococcus faecalis BM4518. We were unable to
      transfer vancomycin resistance from E. faecium 16-346 to E. faecium BM4107 and E.
      faecalis JH2-2. Lastly, transcription of the vanG gene was inducible by
      vancomycin. Conclusions: This is, to the best of our knowledge, the first report
      of a VanG-type vancomycin-resistant strain of E. faecium. Despite the alarm
      pulled because of the therapeutic problems caused by VRE, our work shows that new
      resistant loci can still be found in E. faecium.

PMID- 29346644
TI  - Genome-wide analysis of disease progression in age-related macular degeneration.
AB  - Family- and population-based genetic studies have successfully identified
      multiple disease-susceptibility loci for Age-related macular degeneration (AMD),
      one of the first batch and most successful examples of genome-wide association
      study. However, most genetic studies to date have focused on case-control studies
      of late AMD (choroidal neovascularization or geographic atrophy). The genetic
      influences on disease progression are largely unexplored. We assembled unique
      resources to perform a genome-wide bivariate time-to-event analysis to test for
      association of time-to-late-AMD with ~9 million variants on 2721 Caucasians from
      a large multi-center randomized clinical trial, the Age-Related Eye Disease
      Study. To our knowledge, this is the first genome-wide association study of
      disease progression (bivariate survival outcome) in AMD genetic studies, thus
      providing novel insights to AMD genetics. We used a robust Cox proportional
      hazards model to appropriately account for between-eye correlation when analyzing
      the progression time in the two eyes of each participant. We identified four
      previously reported susceptibility loci showing genome-wide significant
      association with AMD progression: ARMS2-HTRA1 (P = 8.1 * 10-43), CFH (P = 3.5 *
      10-37), C2-CFB-SKIV2L (P = 8.1 * 10-10) and C3 (P = 1.2 * 10-9). Furthermore, we
      detected association of rs58978565 near TNR (P = 2.3 * 10-8), rs28368872 near
      ATF7IP2 (P = 2.9 * 10-8) and rs142450006 near MMP9 (P = 0.0006) with progression
      to choroidal neovascularization but not geographic atrophy. Secondary analysis
      limited to 34 reported risk variants revealed that LIPC and CTRB2-CTRB1 were also
      associated with AMD progression (P < 0.0015). Our genome-wide analysis thus
      expands the genetics in both development and progression of AMD and should assist
      in early identification of high risk individuals.

PMID- 29346645
TI  - Performance of an easy-to-use prediction model for renal patient survival: an
      external validation study using data from the ERA-EDTA Registry.
AB  - Background: An easy-to-use prediction model for long-term renal patient survival
      based on only four predictors [age, primary renal disease, sex and therapy at 90
      days after the start of renal replacement therapy (RRT)] has been developed in
      The Netherlands. To assess the usability of this model for use in Europe, we
      externally validated the model in 10 European countries. Methods: Data from the
      European Renal Association-European Dialysis and Transplant Association (ERA
      EDTA) Registry were used. Ten countries that reported individual patient data to
      the registry on patients starting RRT in the period 1995-2005 were included.
      Patients <16  years of age and/or with missing predictor variable data were
      excluded. The external validation of the prediction model was evaluated for the
      10- (primary endpoint), 5- and 3-year survival predictions by assessing the
      calibration and discrimination outcomes. Results: We used a data set of 136 304
      patients from 10 countries. The calibration in the large and calibration plots
      for 10 deciles of predicted survival probabilities showed average differences of
      1.5, 3.2 and 3.4% in observed versus predicted 10-, 5- and 3-year survival, with
      some small variation on the country level. The concordance index, indicating the
      discriminatory power of the model, was 0.71 in the complete ERA-EDTA Registry
      cohort and varied according to country level between 0.70 and 0.75. Conclusions:
      A prediction model for long-term renal patient survival developed in a single
      country, based on only four easily available variables, has a comparably adequate
      performance in a wide range of other European countries.

PMID- 29346647
TI  - Resistance to Selected Pyrethroid Insecticides in the Malaria Mosquito, Anopheles
      stephensi (Diptera: Culicidae), From Punjab, Pakistan.
AB  - Pyrethroids are commonly used insecticides in malaria control programs; however,
      insecticide resistance limits the benefits gained by using these insecticides. In
      the present study, we assessed the resistance status for different pyrethroids of
      the malaria mosquito vector, Anopheles stephensi Liston (Diptera: Culicidae), in
      the Punjab province, Pakistan. Bioassays were conducted using diagnostic doses
      following standard World Health Organization protocols: 0.05% lambda-cyhalothrin,
      0.75% permethrin, 0.15% cyfluthrin, 0.05% deltamethrin, and 0.1% cypermethrin.
      Field collected An. stephensi from four localities in Punjab (Khanewal, Multan,
      Lodhran, and Bahawalpur) were reared in the laboratory, and non-blood-fed females
      were used in the bioassays. An. stephensi from all the study sites except
      Khanewal were found to be susceptible to permethrin and deltamethrin. Resistance
      or potential resistance to cypermethrin, lambda-cyhalothrin and cyfluthrin was
      observed from all the study sites. The median and 95% knockdown times (KDT50 and
      KDT95) estimates for all the tested insecticides also showed similar responses.
      In conclusion, the study revealed resistance to selected pyrethroids in An.
      stephensi from some parts of Punjab, Pakistan, underscoring the need to devise a
      resistance management strategy for effective control of this important malaria
      vector.

PMID- 29346646
TI  - The Evolutionary History of Nebraska Deer Mice: Local Adaptation in the Face of
      Strong Gene Flow.
AB  - The interplay of gene flow, genetic drift, and local selective pressure is a
      dynamic process that has been well studied from a theoretical perspective over
      the last century. Wright and Haldane laid the foundation for expectations under
      an island-continent model, demonstrating that an island-specific beneficial
      allele may be maintained locally if the selection coefficient is larger than the
      rate of migration of the ancestral allele from the continent. Subsequent
      extensions of this model have provided considerably more insight. Yet, connecting
      theoretical results with empirical data has proven challenging, owing to a lack
      of information on the relationship between genotype, phenotype, and fitness.
      Here, we examine the demographic and selective history of deer mice in and around
      the Nebraska Sand Hills, a system in which variation at the Agouti locus affects
      cryptic coloration that in turn affects the survival of mice in their local
      habitat. We first genotyped 250 individuals from 11 sites along a transect
      spanning the Sand Hills at 660,000 single nucleotide polymorphisms across the
      genome. Using these genomic data, we found that deer mice first colonized the
      Sand Hills following the last glacial period. Subsequent high rates of gene flow
      have served to homogenize the majority of the genome between populations on and
      off the Sand Hills, with the exception of the Agouti pigmentation locus.
      Furthermore, mutations at this locus are strongly associated with the pigment
      traits that are strongly correlated with local soil coloration and thus
      responsible for cryptic coloration.

PMID- 29346648
TI  - EsrB negatively regulates expression of the glutamine sythetase GlnA in the fish
      pathogen Edwardsiella piscicida.
AB  - Edwardsiella piscicida is a gram-negative bacterial pathogen invading a wide
      range of fish species. Response regulator EsrB is essential for the activation of
      type III and type VI secretion systems (T3/T6SS). In this study, proteomes of the
      wild-type E. piscicida EIB202 and DeltaesrB mutant strains were compared to
      identify the regulon components of EsrB cultured in DMEM allowing T3/T6SS
      expression. As a result, 19 proteins showed different expression, which were
      identified to be associated with T3/T6SS, related to amino acid transport and
      metabolism, and energy production. Particularly, GlnA, a glutamine synthetase
      essential for ammonia assimilation and glutamine biosynthesis from glutamate, was
      found to be regulated negatively by EsrB. Moreover, GlnA affected bacterial
      growth in vitro and bacterial colonization in vivo. Collectively, our results
      indicated that EsrB plays important roles in regulating the expression of
      metabolic pathways and virulence genes, including glutamine biosynthesis in E.
      piscicida during infection.

PMID- 29346649
TI  - Endothelial function in rheumatoid arthritis.
AB  - Background: Rheumatoid arthritis (RA) patients are at higher risk of accelerated
      atherosclerosis. Aims: To assess endothelial dysfunction in RA to find a possible
      mechanistic pathway that will explain the clinical phenomenon. Methods: A
      prospective study recruited 44 RA patients with an active long standing (>12
      months) disease. All underwent a detailed assessment of disease activity. To
      estimate the endothelial function the brachial artery method was performed,
      measuring flow mediated diameter percent (FMD%) change. Clustering analyses
      (hierarchical and k-means) were performed. Patients were compared to healthy
      subjects. Results: Forty four RA patients (54.42 +/- 11.14 years, females
      (72.7%)) with co-morbidities (70.5%), not taking tumor necrosis factor-blockers
      or disease modifying anti rheumatic drugs (63.6%). Only 6 (13.6%) had a normal
      endothelial function. Hierarchical and k-means clustering techniques showed
      statistically significant differences among the three clusters concerning disease
      activity score-28 (DAS-28)- erythrocyte sedimentation rate (ESR) (P = 0.000), DAS
      28- C-reactive protein (CRP; P = 0.001), clinical disease activity index (P =
      0.002), simplified disease activity index (P = 0.001), ESR (P = 0.000), (CRP) (P
      = 0.003) and FMD% (P = 0.009). The group with the highest FMD% values exhibited
      the lowest clinical scores and laboratory parameters. Patients with the lowest
      FMD% values co-clustered with subjects with positive but low FMD% changes and
      elevated clinical and laboratory parameters. Conclusions: Our study confirmed the
      feasibility of exploiting endothelial function in clinical practice as an early
      predictor of atherosclerosis in RA patients.

PMID- 29346650
TI  - Persistence of Zika Virus After Birth: Clinical, Virological, Neuroimaging, and
      Neuropathological Documentation in a 5-Month Infant With Congenital Zika
      Syndrome.
AB  - During the Zika epidemic in Brazil, a baby was born at term with microcephaly and
      arthrogryposis. The mother had Zika symptoms at 10 weeks of gestation. At 17
      weeks, ultrasound showed cerebral malformation and ventriculomegaly. At 24 weeks,
      the amniotic fluid contained ZIKV RNA and at birth, placenta and maternal blood
      were also positive using RT-qPCR. At birth the baby urine contained ZIKV RNA,
      whereas CSF at birth and urine at 17 days did not. Seizures started at 6 days.
      EEG was abnormal and CT scan showed cerebral atrophy, calcifications,
      lissencephaly, ventriculomegaly, and cerebellar hypoplasia. Bacterial sepsis at 2
      months was treated. A sudden increase in head circumference occurred at 4 months
      necessitating ventricle-peritoneal shunt placement. At 5 months, the infant died
      with sepsis due to bacterial meningitis. Neuropathological findings were as
      severe as some of those found in neonates who died soon after birth, including
      hydrocephalus, destructive lesions/calcification, gliosis, abnormal neuronal
      migration, dysmaturation of nerve cells, hypomyelination, loss of descending
      axons, and spinal motor neurons. ZIKV RNA was detected only in frozen brain
      tissue using RT-qPCR, but infected cells were not detected by in situ
      hybridization. Progressive gliosis and microgliosis in the midbrain may have
      contributed to aqueduct compression and subsequent hydrocephalus. The etiology of
      progressive disease after in utero infection is not clear and requires
      investigation.

PMID- 29346652
TI  - Toward rational antibody design: recent advancements in molecular dynamics
      simulations.
AB  - Because antibodies have become an important therapeutic tool, rational antibody
      design is a challenging issue involving various science and technology fields.
      From the computational aspect, many types of design-assist methods have been
      developed, but their accuracy is not fully satisfactory. Because of recent
      advancements in computational power, molecular dynamics (MD) simulation has
      become a helpful tool to trace the motion of proteins and to characterize their
      properties. Thus, MD simulation has been applied to various systems involving
      antigen-antibody complexes and has been shown to provide accurate insight into
      antigen-antibody interactions and dynamics at an atomic resolution. Therefore, it
      is highly possible that MD simulation will play several roles complementing the
      conventional antibody design. In this review, we address several important
      features of MD simulation in the context of rational antibody design.

PMID- 29346651
TI  - Bipartite Network Analysis of Gene Sharings in the Microbial World.
AB  - Extensive microbial gene flows affect how we understand virology, microbiology,
      medical sciences, genetic modification, and evolutionary biology. Phylogenies
      only provide a narrow view of these gene flows: plasmids and viruses, lacking
      core genes, cannot be attached to cellular life on phylogenetic trees. Yet
      viruses and plasmids have a major impact on cellular evolution, affecting both
      the gene content and the dynamics of microbial communities. Using bipartite
      graphs that connect up to 149,000 clusters of homologous genes with 8,217 related
      and unrelated genomes, we can in particular show patterns of gene sharing that do
      not map neatly with the organismal phylogeny. Homologous genes are recycled by
      lateral gene transfer, and multiple copies of homologous genes are carried by
      otherwise completely unrelated (and possibly nested) genomes, that is, viruses,
      plasmids and prokaryotes. When a homologous gene is present on at least one
      plasmid or virus and at least one chromosome, a process of "gene
      externalization," affected by a postprocessed selected functional bias, takes
      place, especially in Bacteria. Bipartite graphs give us a view of vertical and
      horizontal gene flow beyond classic taxonomy on a single very large, analytically
      tractable, graph that goes beyond the cellular Web of Life.

PMID- 29346653
TI  - Emergence of acute/subacute infant-juvenile paracoccidioidomycosis in Northeast
      Argentina: Effect of climatic and anthropogenic changes?
AB  - Argentina has two endemic areas of paracoccidioidomycosis (PCM). Bordering
      Paraguay and Brazil, Northeast Argentina (NEA) comprises the area with the
      highest incidence where the chronic adult clinical form has historically been
      reported. Juvenile form in children and adolescents is rare in this area since
      only one case was reported in the last 10 years. Despite this, between 2010 and
      2012, several cases of acute/subacute clinical forms in children aged 10 to 16
      (median 12) were detected. In the last decade, the NEA region has been exposed to
      ecological variations as consequences of certain climatic and anthropogenic
      changes, including El Nino-Southern Oscillation phenomenon during 2009, and
      deforestation. The region has also suffered from the significant ecological
      effects of the construction of one of the biggest hydroelectric dams of South
      America. This study aims to describe clinical and epidemiological aspects of
      acute/subacute PCM cases detected in children from NEA and to discuss climatic
      and anthropogenic changes as possible contributing factors in the emergence of
      this disease in children. This acute/subacute PCM cluster was characterized by
      severe disseminated and aggressive presentations to localized form, with a high
      spectrum of clinical manifestations uncommonly observed. Due to the lack of
      experience in acute/subacute PCM in children in the studied area and the atypical
      clinical manifestations observed, the diagnosis was delayed. In order to avoid
      misdiagnosis, a higher level of suspicion is now required in NEA and countries
      bordering the southern part of the endemic area, which are affected by the
      changes discussed in this article.

PMID- 29346654
TI  - Evaluation of system mapping approaches in identifying patient safety risks.
AB  - Objective: While many system mapping approaches (SMAs) have been broadly used in
      safety-critical industries, few have so far been employed in the healthcare field
      to assist in the identification of patient safety risks. In this study, we
      evaluated a set of system modelling approaches to assess their potential
      contribution to the identification of risks affecting patient safety. The aim was
      to gain a greater understanding of the practical application of system modelling
      approaches with the help of the risk categorization framework developed in this
      study. Setting: We conducted this study in a newly established Adult Attention
      Deficit Hyperactivity Disorder (ADHD) service at Cambridge and Peterborough
      Foundation Trust. Study participants: Eight key stakeholders of the chosen
      service, including clinicians, managers and administrative staff, were
      individually asked to evaluate a set of pre-defined six SMAs according to their
      usefulness in identifying patient safety risks through interview-based
      questionnaires. Results: It was found that each SMA could be useful in the chosen
      healthcare service in different ways. Further, specific types of diagrams were
      selected by stakeholders as more useful than others in identifying different
      sources of risks within the given system. Conclusions: The results of the
      evaluation showed that the system diagram is the most useful SMA in risk
      identification within the given system, while limited time, resources and
      experience of stakeholders with SMAs may present possible obstacles for their
      potential use in the healthcare field in future.

PMID- 29346656
TI  - Host responses to intestinal nematodes.
AB  - Helminth infection remains common in developing countries, where residents who
      suffer from the consequences of such infections can develop serious physical and
      mental disorders and often persist in the face of serious economic problems.
      Intestinal nematode infection induces the development of Th2-type immune
      responses including the B-cell IgE response; additionally, this infection induces
      an increase in the numbers and activation of various types of effector cells,
      such as mast cells, eosinophils and basophils, as well as the induction of goblet
      cell hyperplasia, anti-microbial peptide production and smooth-muscle
      contraction, all of which contribute to expel nematodes. Innate immunity is
      important in efforts to eliminate helminth infection; cytokines, including IL-25,
      IL-33 and thymic stromal lymphopoietin, which are products of epithelial cells
      and mast cells, induce Th2 cells and group 2 innate lymphoid cells to proliferate
      and produce Th2 cytokines. Nematodes also facilitate chronic infection by
      suppression of immune reactions through an increased number of Treg cells.
      Immunosuppression by parasite infection may ultimately be beneficial for the host
      animals; indeed, a negative correlation has been found between parasite infection
      and the prevalence of inflammatory disease in humans.

PMID- 29346655
TI  - Does the Additional Component of Calf Circumference Refine Metabolic Syndrome in
      Correlating With Cardiovascular Risk?
AB  - Context: Calf circumference (CC) was a useful anthropometric tool, but there was
      limited study on the effect of CC on metabolic syndrome (MetS) for cardiovascular
      risk. Objective: The objective of our study was to determine whether adding CC as
      a component of MetS refined correlating MetS with cardiovascular, all-cause, and
      cancer mortality risks. Design, Setting, Patients, and Interventions: From the
      National Health and Nutrition Examination Survey data set for 1999 through 2002,
      we analyzed four types of MetS: (1) increased waist circumference and two or more
      of four MetS components (WaistMetS); (2) decreased CC and two or more of four
      MetS components (CalfMetS); (3) increased waist-to-calf ratio and two or more of
      four MetS components (WCRMetS); and (4) decreased CC and three or more of five
      MetS components (CC+MetS). Primary Outcome Measure: The cause-specific hazard
      ratios were measured as categorized by the four types of MetS. Results: For
      cardiovascular mortality, the adjusted hazard ratios for WaistMetS, CalfMetS,
      WCRMetS, and CC+MetS were 1.867, 1.871, 1.949, and 2.306, respectively (all P <
      0.001). Notably, CalfMetS showed the strongest positive correlation with serum C
      reactive protein levels, and WCRMetS had the strongest positive relationship with
      homeostasis model assessment of insulin resistance. Conclusions: Adding CC to the
      components of MetS correlated with higher cardiovascular and all-cause mortality
      risk than the traditional definition of MetS.

PMID- 29346657
TI  - Perspectives on Queer Music Therapy: A Qualitative Analysis of Music Therapists'
      Reactions to Radically Inclusive Practice.
AB  - Background: The queer music therapy model was designed by Bain, Grzanka, and
      Crowe in 2016 as a novel therapeutic approach to affirm and empower LGBTQ+
      identity through music. No data have been generated on how this model might
      actually be implemented, or the strengths and limitations of the model according
      to music therapy professionals. Objective: The purpose of this study was to build
      on Bain and colleagues' work by collecting music therapists' perspectives on
      queer music therapy and using these data to critically evaluate the model.
      Methods: Semi-structured qualitative interviews were conducted with twelve music
      therapists who identify as LGBTQ+ or have experience working with LGBTQ+ clients.
      Participants were prompted to discuss their music therapy backgrounds,
      experiences with LGBTQ+ clients, and reactions to the queer music therapy model.
      Interviews were analyzed using a critical discourse analysis approach. Results:
      The qualitative findings revealed major strengths of the queer music therapy
      model and ways in which it could be improved by attending to: (a) the structural
      limitations of the music therapy discipline, including the demographic
      composition of the field and lack of critical perspectives in music therapy
      training; and (b) intersectional considerations of ageism and ableism within
      diverse LGBTQ+ populations. Conclusions: Queer music therapy has positive
      implications for future work with LGBTQ+ individuals, but it must more
      substantively integrate intersectionality theory to serve a diverse range of
      LGBTQ+ clients. Further, it must critically attend to the structural limitations
      of the music therapy discipline itself.

PMID- 29346658
TI  - Potential for diet to prevent and remediate cognitive deficits in neurological
      disorders.
AB  - The pathophysiology of many neurological disorders involves oxidative stress,
      neuroinflammation, and mitochondrial dysfunction. There is now substantial
      evidence that diet can decrease these forms of pathophysiology, and an emerging
      body of literature relatedly suggests that diet can also prevent or even
      remediate the cognitive deficits observed in neurological disorders that exhibit
      such pathology (eg, Alzheimer's disease, multiple sclerosis, age-related
      cognitive decline, epilepsy). The current review summarizes the emerging evidence
      in relation to whole diets prominent in the scientific literature-ketogenic,
      caloric restriction, high polyphenol, and Mediterranean diets-and provides a
      discussion of the possible underlying neurophysiological mechanisms.

PMID- 29346659
TI  - Case Report: Facial Nerve Bifurcation Noted During Resection of Vestibular
      Schwannoma.
AB  - BACKGROUND AND IMPORTANCE: Resection of cerebellopontine angle tumors is
      challenging because the proximity of the facial nerve puts it at risk of
      inadvertent injury and subsequent dysfunction. It is critical to consider
      variations in anatomy and be aware of the potential deviations in the course of
      the nerve in order to avoid damage. CLINICAL PRESENTATION: We present a case of a
      facial nerve bifurcation identified during resection of a vestibular schwannoma.
      CONCLUSION: This is the only reported case of proximal facial nerve bifurcation.
      We review what is known about variations in proximal facial nerve anatomy, the
      rates of facial nerve injury after schwannoma resection, and the importance of
      neuromonitoring in identifying the nerve and predicting function postoperatively.
      Ultimately, understanding possible anatomic variations in the nerve is critical
      to minimize iatrogenic injury during surgery.

PMID- 29346660
TI  - Herpes zoster and Hutchinson's sign.

PMID- 29346661
TI  - The role of healthcare and education systems in co-occurrence of health risk
      behaviours in 27 European countries.
AB  - Background: Contextual factors play an important role in health and related
      behaviours. This study aims to examine the association of co-occurrence of five
      health-risk behaviours with healthcare and education contextual factors using
      nationally representative samples from 27 European countries. Methods: Data were
      from Eurobarometer 72.3, 2009. The outcome was a count variable ranging from 0 to
      5 indicating co-occurrence of five health-risk behaviours, namely smoking,
      excessive alcohol consumption, non-frequent fresh fruit consumption, physical
      inactivity and non-dental check-ups. Public expenditures on healthcare and
      education as a percentage of GDP and quality of healthcare and education at a
      country-level were used as contextual factors. A set of multilevel Poisson
      regression models were conducted to examine the associations between co
      occurrence of health-risk behaviours and each of the contextual factors
      considering age, gender, marital status, urbanisation, individual socioeconomic
      positions (education, subjective social status or difficulty in paying bills) and
      GDP per capita. Results: The total population was 23 842. Greater expenditures on
      healthcare and education, and better quality of healthcare systems had negative
      associations with co-occurrence of health-risk behaviours in the model adjusted
      for all individual demographic indicators. However, statistical significance
      disappeared after adjusting for socioeconomic indicators and GDP per capita.
      Conclusion: While the study highlights the importance of developing high-quality
      healthcare and education systems generously supported by public fund in relation
      to co-occurrence of health-risk behaviours, the influence of contextual factors
      in adopting health-related behaviours is probably attenuated by individual
      socioeconomic factors.

PMID- 29346662
TI  - Shifting determinants of health inequalities in unstable times: Portugal as a
      case study.
AB  - Background: We explore how health inequalities (HI) changed in Portugal over the
      last decade, considering it is one of the most unequal European countries and has
      gone through major economic changes. We describe how inequalities in limitations
      changed considering different socioeconomic determinants, in order to understand
      what drove changes in HI. Methods: We used cross-sectional waves from the
      European Survey on Income and Living Conditions database to determine how
      inequalities in health limitations changed between 2004 and 2014 in Portugal in
      residents aged 16 years and over. We calculated prevalence estimates of
      limitations and differences between income terciles, the concentration index for
      each year and its decomposition and multiple logistic regressions to estimate the
      association between socioeconomic determinants and limitations. Results: The
      prevalence of health limitations increased in Portugal since 2004, especially
      after 2010, from 35 to 47%. But the difference between top and bottom income
      terciles decreased from 23 to 10 percentage points, as richer people experienced
      a steeper increase. This was driven by an increase in prevalence among
      economically active people, who, from 2011 onwards, had more limitations (OR and
      95% CI were 2.42 [2.13-2.75] in 2004 and 0.71 [0.65-0.78] in 2014). Conclusion:
      These results suggest worsening health in Portugal in the last decade, possibly
      connected to periods of economic instability. However, absolute HI decreased
      considerably in the same period. We discuss the possible role of diverse
      adaptation capacity of socioeconomic groups, and of high emigration rates of
      young, healthier people, reflecting another side of the 'migrant health effect'.

PMID- 29346664
TI  - Challenges for prevention research.

PMID- 29346663
TI  - Resident participation in neighbourhood audit tools - a scoping review.
AB  - Background: Healthy urban environments require careful planning and a testing of
      environmental quality that goes beyond statutory requirements. Moreover, it
      requires the inclusion of resident views, perceptions and experiences that help
      deepen the understanding of local (public health) problems. To facilitate this,
      neighbourhoods should be mapped in a way that is relevant to them. One way to do
      this is participative neighbourhood auditing. This paper provides an insight into
      availability and characteristics of participatory neighbourhood audit
      instruments. Methods: A scoping review in scientific and grey literature,
      consisting of the following steps: literature search, identification and
      selection of relevant audit instruments, data extraction and data charting
      (including a work meeting to discuss outputs), reporting. Results: In total, 13
      participatory instruments were identified. The role of residents in most
      instruments was as 'data collectors'; only few instruments included residents in
      other audit activities like problem definition or analysis of data. The
      instruments identified focus mainly on physical, not social, neighbourhood
      characteristics. Paper forms containing closed-ended questions or scales were the
      most often applied registration method. Conclusions: The results show that
      neighbourhood auditing could be improved by including social aspects in the audit
      tools. They also show that the role of residents in neighbourhood auditing is
      limited; however, little is known about how their engagement takes place in
      practice. Developers of new instruments need to balance not only social and
      physical aspects, but also resident engagement and scientific robustness.
      Technologies like mobile applications pose new opportunities for participative
      approaches in neighbourhood auditing.

PMID- 29346665
TI  - Moving towards compulsory vaccination: the Italian experience.

PMID- 29346666
TI  - Gypsy, Roma and Traveller access to and engagement with health services: a
      systematic review.
AB  - Background: Gypsy, Roma and Traveller people represent the most disadvantaged
      minority groups in Europe, having the poorest health outcomes. This systematic
      review addressed the question of how Gypsy, Roma and Traveller people access
      healthcare and what are the best ways to enhance their engagement with health
      services. Methods: Searches were conducted in 21 electronic databases
      complemented by a focussed Google search. Studies were included if they had
      sufficient focus on Gypsy, Roma or Traveller populations; reported data pertinent
      to healthcare service use or engagement and were published in English from 2000
      to 2015. Study findings were analyzed thematically and a narrative synthesis
      reported. Results: Ninety-nine studies from 32 countries were included, covering
      a range of health services. Nearly one-half of the presented findings related to
      primary healthcare services. Reported barriers to health service usage related to
      organisation of health systems, discrimination, culture and language, health
      literacy, service-user attributes and economic barriers. Promising engagement
      strategies included specialist roles, outreach services, dedicated services,
      raising health awareness, handheld records, training for staff and collaborative
      working. Conclusion: This review provides evidence that Gypsy, Roma and Traveller
      populations across Europe struggle to exercise their right to healthcare on
      account of multiple barriers; and related to other determinants of disadvantage
      such as low literacy levels and experiences of discrimination. Some promising
      strategies to overcome barriers were reported but the evidence is weak;
      therefore, rigorous evaluations of interventions to improve access to and
      engagement with health services for Gypsy, Roma and Traveller people are needed.

PMID- 29346667
TI  - The Results of Hemoglobin Variant Analysis in Patients Revealing Microcytic
      Erythrocytosis on Complete Blood Count.
AB  - Background: Microcytic erythrocytosis is an underrecognized and underevaluated
      complete blood count (CBC) finding. The literature pertaining to the
      determination of its etiology specifically by hemoglobin variant analysis is
      limited. Methods: We performed hemoglobin variant analysis by high performance
      liquid chromatography on 137 patients who revealed microcytic erythrocytosis on
      CBC, and reviewed the results for the diagnosis of hemoglobin-associated
      disorders. Results: A diagnosis of thalassemia trait and/or a hemoglobinopathy
      was established in 93 of 137 (67.9%) patients. Amongst these, beta-thalassemia
      trait topped the list with 69 cases (74.1%), followed by hereditary persistence
      of fetal hemoglobin with 5 cases (5.5%), Hemoglobin E disease with 4 cases
      (4.3%), and ?/beta-thalassemia with 2 cases (2.1%). Compound heterozygous
      conditions with 1 or more hemoglobinopathies and/or thalassemias were diagnosed
      in 13 cases (14.0%). Abnormal hemoglobins in the compound heterozygosity group
      included C, S, HPFH, and 2 unknowns. Conclusion: Hemoglobin variant analysis
      provided a very high positive yield in determining the etiology of microcytic
      erythrocytosis.

PMID- 29346669
TI  - Regulation of mitotic recombination between DNA repeats in centromeres.

PMID- 29346668
TI  - RAD51 and RTEL1 compensate telomere loss in the absence of telomerase.
AB  - Replicative erosion of telomeres is naturally compensated by telomerase and
      studies in yeast and vertebrates show that homologous recombination can
      compensate for the absence of telomerase. We show that RAD51 protein, which
      catalyzes the key strand-invasion step of homologous recombination, is localized
      at Arabidopsis telomeres in absence of telomerase. Blocking the strand-transfer
      activity of the RAD51 in telomerase mutant plants results in a strikingly earlier
      onset of developmental defects, accompanied by increased numbers of end-to-end
      chromosome fusions. Imposing replication stress through knockout of RNaseH2
      increases numbers of chromosome fusions and reduces the survival of these plants
      deficient for telomerase and homologous recombination. This finding suggests that
      RAD51-dependent homologous recombination acts as an essential backup to the
      telomerase for compensation of replicative telomere loss to ensure genome
      stability. Furthermore, we show that this positive role of RAD51 in telomere
      stability is dependent on the RTEL1 helicase. We propose that a RAD51 dependent
      break-induced replication process is activated in cells lacking telomerase
      activity, with RTEL1 responsible for D-loop dissolution after telomere
      replication.

PMID- 29346670
TI  - SCOPING ANALYSIS OF MATERIAL ACTIVATION AT A BORON NEUTRON CAPTURE THERAPY
      FACILITY BASED ON THE Be(p,xn) REACTION WITH 30 MeV PROTONS.
AB  - Material activation assessment of a proposed accelerator-based boron neutron
      capture therapy facility was performed using the FLUKA Monte Carlo code to
      quantify the magnitude of the problem in terms of the isotope inventories,
      induced activities, and residual dose rates. Two simplified operation scenarios
      were considered: a 30-min proton bombardment to simulate a typical session of
      patient treatment and a long-term 1 year continuous operation to estimate the
      accumulation of long-lived radionuclides. Following the generation and transport
      of decay radiation, the space- and time-dependent inventories of induced
      radionuclides in materials and residual dose rates after shutdown were obtained.
      The predicted results were compared with the corresponding regulatory limits.
      Moreover, the effectiveness of various measures to reduce the impact of material
      activation was demonstrated.

PMID- 29346671
TI  - Hematological Analysis in Thai Samples With Deletional and Nondeletional HbH
      Diseases.
AB  - Objectives: To compare hematological parameters between deletional and
      nondeletional HbH diseases, and to investigate the correlation between HbH levels
      and hematological parameters within these 2 groups. Methods: Samples of 43
      deletional HbH diseases, which included 39 --SEA/-alpha3.7, 4 - -SEA/-alpha4.2,
      and 22 nondeletional HbH diseases (- -SEA/alphacsalpha), were used in this study.
      Correlations between HbH levels and hematological parameters within these 2
      groups were analyzed. Results: The deletional HbH disease had higher levels of
      RBC counts, total Hb, pack cell volume (PCV), mean corpuscular Hb (MCH), mean
      corpuscular Hb concentration (MCHC), HbA, and HbA2 than did the nondeletional HbH
      disease. A negative correlation between HbH and RBC counts was detected in the
      group of deletional HbH disease, while a positive correlation between HbH and RBC
      counts, total Hb, and PCV was found in the group of nondeletional HbH disease.
      Conclusions: These results reflected that samples with nondeletional HbH showed
      more anemic features than those with the deletional HbH.

PMID- 29346672
TI  - Learning to Live With Schizoaffective Disorder: A Transformative Journey Toward
      Recovery.

PMID- 29346673
TI  - Commentary on "The Potential of Cannabidiol Treatment for Cannabis Users With
      Recent-Onset Psychosis".

PMID- 29346674
TI  - Integrating Research Techniques to Improve Quality and Safety in the
      Preanalytical Phase.
AB  - Background: Reducing errors in the preanalytical phase is difficult, which
      suggests the issue may be multidimensional. As such, qualitative research may be
      truly innovative in this context. Method: We carried out a descriptive study
      using a qualitative method incorporating 4 focus groups. Data analysis followed
      the principles of Grounded Theory. Results: We queried in each of the 4 focus
      groups collectively to identify weaknesses in the system. Those weaknesses that
      were most cited were logistics, coupled with uneven compliance with regulations.
      Conclusion: All 4 focus groups mapped out directives for future work, so that
      regulatory aspects, process management, communication and resources could be
      identified as key areas where error reduction is critical.

PMID- 29346675
TI  - In search of the best xenogeneic material for a paediatric conduit: an
      experimental study.
AB  - OBJECTIVES: The development of calcification-resistant bioprosthetic materials is
      a very important challenge for paediatric surgery. The subcutaneous implantation
      in rats is the well-known first-stage model for this kind of research. Using this
      model, we aimed to compare calcification of the porcine aortic wall and bovine
      pericardium and jugular vein wall cross-linked with glutaraldehyde (GA) and
      ethylene glycol diglycidyl ether (DE). We also determined the efficacy of DE
      preserved tissue modification with 2-(2-carboxyethylamino)ethylidene-1,1
      bisphosphonic acid (CEABA). METHODS: Three groups of each biomaterial were
      evaluated: GA-treated, DE-treated and DE + CEABA-treated. The microstructure of
      non-implanted biomaterials was assessed by light microscopy after Picro Mallory
      staining; the phosphorus content of the DE and DE + CEABA samples was assessed by
      atomic emission spectrometry. Samples were implanted subcutaneously into young
      rats for 10 and 60 days. The explant end-point included quantitative
      calcification assessment by atomic absorption spectrophotometry and light
      microscopy examination after von Kossa staining. RESULTS: All GA-treated
      biomaterials had a high calcium-binding capacity (>100 MUg/mg dry tissue). DE
      preservation decreased the vein wall and pericardium calcium content by 4- and 40
      fold, respectively, but was ineffective for the aortic wall. The calculated CEABA
      content was almost equal in the vein wall and pericardium (17.7 and 18.5 MUM/g)
      and slightly less in the aortic wall (15 MUM/g) (P = 0.011). CEABA effectively
      reduced mineralization in the DE aortic wall and DE pericardium to 10.1 (7.8
      21.1) and 0.95 (0.57-1.38) MUg/mg but had no effect in the DE vein wall.
      Mineralization in the GA- and DE-treated aortic and vein walls was predominantly
      associated with elastin. CEABA modification decreased elastin calcification but
      did not block it completely. CONCLUSIONS: Each xenogeneic material requires
      individual anticalcification strategy. DE + CEABA pretreatment demonstrates a
      high mineralization-blocking efficacy for the bovine pericardium and should be
      employed to further develop the paediatric pericardial conduit. Aortic wall
      calcification cannot be blocked completely using this strategy.

PMID- 29346676
TI  - Familial hypercholesterolemia: xanthelasma, corneal arcus and tendon xanthomas,
      only in severe forms.

PMID- 29346677
TI  - Anatomical explanations for acute depressions in radial pattern of axial sap flow
      in two diffuse-porous mangrove species: implications for water use.
AB  - Mangrove species have developed uniquely efficient water-use strategies in order
      to survive in highly saline and anaerobic environments. Herein, we estimated the
      stand water use of two diffuse-porous mangrove species of the same age,
      Sonneratia apetala Buch. Ham and Sonneratia caseolaris (L.) Engl., growing in a
      similar intertidal environment. Specifically, to investigate the radial patterns
      of axial sap flow density (Js) and understand the anatomical traits associated
      with them, we measured axial sap flow density in situ together with
      micromorphological observations. A significant decrease of Js was observed for
      both species. This result was accompanied by the corresponding observations of
      wood structure and blockages in xylem sapwood, which appeared to influence and,
      hence, explained the acute radial reductions of axial sap flow in the stems of
      both species. However, higher radial resistance in sapwood of S. caseolaris
      caused a steeper decline of Js radially when compared with S. apetala, thus
      explaining the latter's more efficient use of water. Without first considering
      acute reductions in Js into the sapwood from the outer bark, a total of ~55% and
      51% of water use would have been overestimated, corresponding to average
      discrepancies in stand water use of 5.6 mm day-1 for S. apetala trees and 2.5 mm
      day-1 for S. caseolaris trees. This suggests that measuring radial pattern of Js
      is a critical factor in determining whole-tree or stand water use.

PMID- 29346678
TI  - Case study of an adaptation and implementation of a Diabetes Prevention Program
      for individuals with serious mental illness.
AB  - The Diabetes Prevention Program (DPP) is an evidence-based lifestyle intervention
      developed to decrease the risk for type 2 diabetes and promote weight loss in
      individuals at risk for diabetes. Individuals with serious mental illness have a
      greater risk for developing diabetes compared with the general population. In
      this article, the authors provide a detailed description of the adaptation
      process of the DPP for individuals with serious mental illness (DPP-SMI). The
      adaptation process was based on a cultural adaptation framework for modifying
      evidence-based interventions. To assess the effectiveness of the DPP-SMI, 11
      individuals from a community mental health residential agency completed a 22
      session pilot study of the adapted program and provided physiological measures
      before and after the intervention. As primary outcomes, participants were
      expected to report decreased body weight and increased physical activity per
      week. Completers had an average weight loss of 19 lbs (8%) and their physical
      activity increased from 161 to 405 min per week. These preliminary results
      together with participants' feedback informed further refinement of the DPP-SMI.
      This case study supports that individuals with serious mental illness can benefit
      from the DPP-SMI, which is tailored to meet the unique needs of this population
      group.

PMID- 29346679
TI  - Risk stratification in Takotsubo syndrome: a role of mitral annular plane
      systolic excursion.
AB  - Aim: Takotsubo syndrome (TTS) patients have a higher mortality rate than the
      general population. Our study was conducted to determine the short- and long-term
      outcome of TTS patients associated with a significantly compromised mitral
      annular plane systolic excursion (MAPSE) on hospital admission. Methods and
      results: Our institutional database constituted a collective of 53 patients
      diagnosed with TTS between 2003 and 2016. The patients were classified into two
      groups based on the MAPSE, with those presenting with an MAPSE <1 cm on admission
      categorized into one group (n = 20, 38%) and those presenting with MAPSE >=1 cm
      (n = 33, 62%) categorized into another group. Preliminary results indicated that
      patients with an MAPSE < 1 cm had a greater risk of developing thromboembolic
      events. The long-term mortality was significantly higher in TTS patients with an
      MAPSE < 1 cm. In the multivariate Cox regression analysis, cardiogenic shock
      (hazard ratio 3.5; 95% confidence interval: 1.2-10.7; P = 0.02) and MAPSE < 1 cm
      (hazard ratio 5.1; 95% confidence interval: 1.3-19.2; P = 0.01) figured as
      independent predictors of the mortality. Conclusion: Although the short-term
      mortality rates among TTS patients diagnosed with a reduced MAPSE on admission
      were as similar as without reduced MAPSE, the long-term mortality rates among TTS
      patients diagnosed with a reduced MAPSE on admission were significantly higher.
      There is an urgent need for randomized trials, which could help define uniform
      clinical management strategies for high-risk TTS patients.

PMID- 29346680
TI  - Conjunctival petechiae and infective endocarditis.

PMID- 29346681
TI  - Optimal number and sizes of the doses in fractionated radiotherapy according to
      the LQ model.
AB  - We address a non-linear programming problem to find the optimal scheme of dose
      fractionation in cancer radiotherapy. Using the LQ model to represent the
      response to radiation of tumour and normal tissues, we formulate a constrained
      non-linear optimization problem in terms of the variables number and sizes of the
      dose fractions. Quadratic constraints are imposed to guarantee that the damages
      to the early and late responding normal tissues do not exceed assigned tolerable
      levels. Linear constraints are set to limit the size of the daily doses. The
      optimal solutions are found in two steps: i) analytical determination of the
      optimal sizes of the fractional doses for a fixed, but arbitrary number of
      fractions n; ii) numerical simulation of a sequence of the previous optima for n
      increasing, and for specific tumour classes. We prove the existence of a finite
      upper bound for the optimal number of fractions. So, the optimum with respect to
      n is found by means of a finite number of comparisons amongst the optimal values
      of the objective function at the first step. In the numerical simulations, the
      radiosensitivity and repopulation parameters of the normal tissue are fixed,
      while we investigate the behaviour of the optimal solution for wide variations of
      the tumour parameters, relating our optima to real clinical protocols. We
      recognize that the optimality of hypo or equi-fractionated treatment schemes
      depends on the value of the tumour radiosensitivity ratio compared to the normal
      tissue radiosensitivity. Fast growing, radioresistant tumours may require
      particularly short optimal treatments.

PMID- 29346683
TI  - Strigolactones: mediators of osmotic stress responses with a potential for
      agrochemical manipulation of crop resilience.
AB  - After quickly touching upon general aspects of strigolactone biology and
      functions, including structure, synthesis, and perception, this review focuses on
      the role and regulation of the strigolactone pathway during osmotic stress, in
      light of the most recent research developments. We discuss available data on
      organ-specific dynamics of strigolactone synthesis and interaction with abscisic
      acid in the acclimatization response, with emphasis on the ecophysiological
      implications of the effects on the stomatal closure process. We highlight the
      importance of considering roots and shoots separately as well as combined versus
      individual stress treatments; and of performing reciprocal grafting experiments
      to work out organ contributions and long-distance signalling events and
      components under more realistic conditions. Finally, we elaborate on the question
      of if and how synthetic or natural strigolactones, alone or in combination with
      crop management strategies such as grafting, hold potential to maximize crop
      resilience to abiotic stresses.

PMID- 29346682
TI  - Receptor Usage of a Novel Bat Lineage C Betacoronavirus Reveals Evolution of
      Middle East Respiratory Syndrome-Related Coronavirus Spike Proteins for Human
      Dipeptidyl Peptidase 4 Binding.
AB  - Although bats are known to harbor Middle East Respiratory Syndrome coronavirus
      (MERS-CoV)-related viruses, the role of bats in the evolutionary origin and
      pathway remains obscure. We identified a novel MERS-CoV-related betacoronavirus,
      Hp-BatCoV HKU25, from Chinese pipistrelle bats. Although it is closely related to
      MERS-CoV in most genome regions, its spike protein occupies a phylogenetic
      position between that of Ty-BatCoV HKU4 and Pi-BatCoV HKU5. Because Ty-BatCoV
      HKU4 but not Pi-BatCoV HKU5 can use the MERS-CoV receptor human dipeptidyl
      peptidase 4 (hDPP4) for cell entry, we tested the ability of Hp-BatCoV HKU25 to
      bind and use hDPP4. The HKU25-receptor binding domain (RBD) can bind to hDPP4
      protein and hDPP4-expressing cells, but it does so with lower efficiency than
      that of MERS-RBD. Pseudovirus assays showed that HKU25-spike can use hDPP4 for
      entry to hDPP4-expressing cells, although with lower efficiency than that of MERS
      spike and HKU4-spike. Our findings support a bat origin of MERS-CoV and suggest
      that bat CoV spike proteins may have evolved in a stepwise manner for binding to
      hDPP4.

PMID- 29346684
TI  - Comparing Cortical Trajectory Transforaminal Lumbar Interbody Fusions Against
      Pedicle Trajectory Transforaminal Lumbar Interbody Fusions and Posterolateral
      Fusions: A Retrospective Cohort Study of 90-day Outcomes.
AB  - BACKGROUND: The cortical screw (CS) trajectory for pedicle screw placement is
      believed to require a smaller incision and less tissue dissection resulting in
      lower blood loss and faster healing; however, this has not yet been confirmed in
      clinical studies. OBJECTIVE: To compare CS transforaminal lumbar interbody
      fusions (TLIF), traditional pedicle screw (TPS) trajectory TLIFs, and
      posterolateral fusion (PLF) without interbody for differences in operative
      characteristics and complications. METHODS: We performed a retrospective cohort
      study (CS, TPS, and PLF) looking at patients who underwent lumbar fusion with 1
      or 2 levels. Extracted data included demographics, comorbidities, estimated blood
      loss, transfusions, operative time, length of stay, discharge disposition (home
      vs rehabilitation), and complications within the perioperative, 30- and 90-d
      periods. RESULTS: A total of 118 patients (45 CS, 35 TPS, and 38 PLF) were
      included with average age 62 and 90-d follow-up for 106 (90%) patients. CS had
      less average blood loss (231 ml) than either TPS (424, P = .0023) or PLF (400, P
      = .0070). CS had far fewer transfusions than either TPS or PLF (P < .0001). TPS
      had longer average operating room (OR) time (262 min) than either CS (214, P =
      .0075) or PLF (211, P = .0060). CS had the shortest length of postoperative stay
      (4.3 days) which was significantly shorter than PLF (6.2, P = .0138) but not
      different than TPS (4.8). There were no differences in discharge disposition,
      complications, perioperative, 30-d, 90-d, durotomy, or wound healing issues.
      CONCLUSION: The CS trajectory is associated with less blood loss, fewer
      transfusions, reduced OR time, and shorter length of stay, with no difference in
      complications.

PMID- 29346685
TI  - Metabolic Flux Engineering of Cembratrien-ol Production in Both the Glandular
      Trichome and Leaf Mesophyll in Nicotiana tabacum.
AB  - Cembratrien-ol synthase (CBTS) catalyzes the first step in cembranoid
      biosynthesis, producing cembratrien-ols in plant trichomes. In our previous
      study, microarray transcriptomes between leaves with trichomes and leaves without
      trichomes showed that an NtCBTS2 gene was expressed exclusively and abundantly in
      trichomes. Here, two NtCBTS2 isogenes (NtCBTS2a and NtCBTS2b), derived from a
      diploid genome donor, Nicotiana sylvestris, were identified from N. tabacum. Both
      genes were expressed primarily in trichomes, with relatively decreased
      transcription in flowers and stems, and faint expression in roots, and no
      expression was detected in leaves lacking trichomes. To demonstrate the
      feasibility of producing natural product cembratrien-ols in tobacco mesophylls,
      the mesophylls of 35S:NtCBTS2b transgenic tobacco plants were used in the
      analysis, suggesting that constitutive expression of NtCBTS2b led to the
      cembratrien-ol production in mesophylls. Overexpression of NtCBTS2b using either
      Cauliflower mosaic virus (CaMV) 35S or trichome-specific Cyt P450 oxygenase (CYP)
      promoters greatly increased aphid resistance by promoting the accumulation of CBT
      ols, increased the secretory cell growth in glandular trichomes and increased the
      levels of various physiological measures, including sugar esters, gibberellins,
      and cembranoid production. Meanwhile, specifically overexpressing NtCBTS2b in
      glandular trichomes could most efficiently promote aphid resistance in tobacco
      plants. Notably, our results indicate the feasibility of utilizing bio
      engineering to produce large amounts of CBT-ols, and modify significantly the
      composition of naturally produced CBT-ols and CBT-diols, thereby promoting aphid
      resistance in plants.

PMID- 29346689
TI  - Initial Development and Validation of a Family Medicine Attitudes Questionnaire.
AB  - BACKGROUND AND OBJECTIVES: Although many curricular and policy interventions are
      designed to influence students' attitudes toward family medicine, assessment of
      these interventions is limited by lack of a comprehensive, validated measure of
      students' attitudes. We sought to develop and validate a questionnaire that
      effectively assesses medical student attitudes toward family medicine. METHODS: A
      31-item questionnaire was assessed for internal, external, and content validity.
      The questionnaire was offered to fourth-year students at two Midwestern medical
      schools. Internal validity was assessed using data reduction and iterative factor
      analyses. External validity was assessed by correlating scores with intention to
      match in family medicine. Content validity was assessed by directly observing
      students as they completed the questionnaire and qualitatively evaluating student
      comments. RESULTS: Of 858 students invited, 426 (49.7%) provided usable
      questionnaire data. After removal of questions with lower interitem correlations
      and simplification of subscales, the modified questionnaire achieved acceptable
      subscale internal consistency and a Cronbach alpha of 0.798. The overall
      instrument summative score correlated with family medicine career choice
      (P<0.001). Most subscales and individual items also correlated with family
      medicine choice. Ten students were directly observed, using an iterative process,
      and modifications were made based on student understanding. CONCLUSIONS:
      Development of a validated questionnaire assessing medical student attitudes
      toward family medicine is feasible. With further refinement, the Family Medicine
      Attitudes Questionnaire may be useful in evaluating the impact of curricular
      interventions on students' perceptions of family medicine, contributing to an
      evidence-based approach to recruitment of students to the specialty.

PMID- 29346690
TI  - Using Standardized Patient Assessments to Evaluate a Health Literacy Curriculum.
AB  - BACKGROUND AND OBJECTIVES: Patients' health literacy is a growing concern as
      patients are expected to perform more self-care. While many US schools implement
      health literacy in their curricula, time spent on the topic ranges from 0 to 8
      hours and is largely didactic. Evaluation of health literacy skills is not well
      defined. The effectiveness of a health literacy curriculum for third-year medical
      students was evaluated by two standardized patients assessments (SPAs). METHODS:
      All third-year medical students complete a required 4-week clerkship in family
      medicine. After participating in seminars on patient-centered communication,
      health literacy, mindfulness, implicit bias, and chronic disease management,
      students complete SPA-1. Students also work in two team-based teaching clinics
      with chronic disease patients with limited health literacy and receive faculty
      feedback. At week 4, students complete SPA-2. Six raters evaluated all video
      recorded SPA performances using the Common Ground validated instrument and a
      tailored health literacy skills checklist. RESULTS: Using SPAs and reliably
      trained nonclinical raters is an effective method for training and evaluating
      students about health literacy. Two classes (2013 and 2015) had significant
      improvement in Common Ground core skills from SPA-1 to SPA-2. For all classes, a
      small but significant increase in student use of health literacy checklist was
      seen from SPA-1 to SPA-2. CONCLUSIONS: Didactic sessions prepare students to
      demonstrate competence on Common Ground and health literacy skills. Improvements
      in students' health literacy and communication skills are feasible in a 4-week
      clerkship utilizing the curriculum and evaluation process described.

PMID- 29346691
TI  - The Impact of Near-Peer Teaching on Medical Students' Transition to Clerkships.
AB  - BACKGROUND AND OBJECTIVES: The transition to clerkships is one of the most
      challenging times during medical school. To help students better cope, many
      schools have established transition-to-clerkship curricula. Such curricula may
      optimally prepare students through increasing their self-efficacy and response
      efficacy. We hypothesized that a small-group, near-peer-led format would be
      ideally suited to help students achieve these outcomes. METHODS: During process
      improvement for a transition-to-clerkship curriculum, we conducted an informal
      focus group and subsequent survey of postclerkship students to guide curricular
      innovation, including incorporation of third- and fourth-year students as near
      peer instructors in a seminar format. Seminars included three sequential small
      group discussions focused on discrete topic areas and concluded with a large
      group session highlighting salient discussion points. To evaluate the impact of
      this educational strategy, near-peer learners were surveyed before and after the
      seminars. RESULTS: Junior student participants reported feeling more prepared to
      integrate into the health care team, develop a clerkship study plan, and access
      applicable, valuable study materials, both immediately following the seminars and
      6 months later, demonstrating increased self-efficacy. These students placed
      equal or greater value on these topics as compared to students in previous year
      groups, demonstrating similar response efficacy. CONCLUSIONS: This study
      demonstrated an increase in student self-efficacy that persisted 6 months
      postintervention, in addition to similar response efficacy. Future research could
      be directed toward: (1) investigating whether improvements in self-efficacy among
      students transitioning to clerkships are associated with improved clerkship
      performance and (2) studying outcomes for near-peer teachers.

PMID- 29346692
TI  - US Federal Policies Should Better Support the Primary Care Physician Workforce.

PMID- 29346693
TI  - Clinical Experience in Medical School.

PMID- 29346694
TI  - Vocation, Autonomy, Agency, and Meaning.

PMID- 29346695
TI  - Symbols and Rituals of Healing.

PMID- 29346696
TI  - An Unlikely Job Search Leads Home.

PMID- 29346697
TI  - Surviving End-of-Life Care.

PMID- 29346698
TI  - Procedural Knowledge and Skills of Residents Entering Canadian Family Medicine
      Programs in Alberta.
AB  - BACKGROUND AND OBJECTIVES: Incoming family medicine (FM) residents start
      residency with different levels of procedural training. Understanding their
      baseline skill level is necessary to plan the educational experiences and
      teaching methods that will provide the desired knowledge, skills, and attitudes
      related to performing medical procedures. METHODS: A survey of 69 procedures
      based on the core list issued by the College of Family Physicians of Canada was
      administered to incoming residents in Alberta (Calgary and Edmonton FM programs).
      The survey intended to identify the levels of training and confidence acquired
      for each listed procedure before residency, and plans to perform each of the
      procedures in future independent practice. RESULTS: A total of 146 residents from
      both programs responded to the survey (82% response rate). Of the 69 procedures
      evaluated, 15 (21.7%) had been previously performed at least five times by 50% or
      more residents. Only five procedures were rated by 80% or more of the residents
      as being able to perform independently or to teach to others: simple suture,
      infiltration of local anesthetic, intramuscular injection, cryotherapy of skin
      lesions and Pap smear. More male residents than female residents felt confident
      in performing 10 procedures, while female residents were more confident in
      performing Pap smears. Rural residents felt more confident to perform 22
      procedures than their urban colleagues. CONCLUSIONS: This information
      demonstrates limited prior training in procedures among entering residents, and
      provides guidance to FM programs to develop teaching interventions to achieve
      competence in those procedural skills seen as necessary for family physicians.

PMID- 29346699
TI  - Teaching Chronic Pain in the Family Medicine Residency.
AB  - BACKGROUND AND OBJECTIVES: Chronic pain is a significant condition affecting many
      Americans. Primary care physicians play an important role in chronic pain
      management, but many residents and physicians feel poorly prepared to manage it.
      METHODS: Data were collected as part of the 2016 Council of Academic Family
      Medicine Educational Research Alliance (CERA) Program Director Survey, which was
      sent electronically to 484 program directors in the United States. The authors
      sought to determine whether residency directors' attitudes about treating chronic
      pain were associated with the amount of time devoted to teaching family medicine
      residents about chronic pain assessment, therapy (use of opioids, use adjuvant
      pain medications, use of other nonopioids, use of nonpharmacological treatments),
      and risk management (risk assessment, use of pain management contracts, informed
      consent when prescribing opioids, and urine drug monitoring). Attitudes were
      assessed by asking whether: (1) chronic pain is best managed by a primary care
      physician (PCP); (2) prescribing opioid medications is time consuming; (3)
      prescribing opioids is high-risk; (4) prescribing opioids contributes to opioid
      misuse; and (4) effective nonopioid treatments exist. An additional question
      assessed confidence in treating chronic pain. RESULTS: The response rate was 53%.
      The average family medicine residency devotes about 33 hours to education about
      pain management topics including 5.4 hours on chronic pain assessment, 16.2 hours
      on therapy, and 11.4 hours on risk assessment. Residency directors' belief that
      there are effective nonopioid treatments for chronic pain was the only attitude
      item that was associated with teaching about chronic pain. CONCLUSIONS: Residency
      directors' attitudes do not predict the time devoted to teaching chronic pain in
      family medicine residencies.

PMID- 29346700
TI  - Competence Revisited in a Rural Context.
AB  - BACKGROUND AND OBJECTIVES: General competencies developed in undergraduate and
      graduate medical education are sometimes promoted as applicable in any practice
      context. However, rural practice presents challenges and opportunities that may
      require unique training. The objectives of this national survey of both
      undergraduate and graduate medical educators and practicing physicians were to
      further develop a previously published list of competency domains for working in
      rural communities and to assess their relative importance in education and
      practice. METHODS: Using six rural competency domains first refined with a
      national group at the Society of Teachers of Family Medicine Annual Meeting in
      Baltimore in 2008, the authors employed a snowball strategy to survey medical
      educators and physicians regarding the importance and relevance of this list and
      to solicit additional domains and competencies. RESULTS: All six domains were
      considered important, with average responses for each domain ranging from 4.16 to
      4.78 on a 5-point Likert scale (1-not important; 5-extremely important). Unique
      relevance to rural practice was more varied, with average responses for domains
      ranging from 2.36 to 3.6 (1-not at all unique; 5-extremely unique). Analysis of
      free text responses identified two important new domains-Comprehensiveness and
      Agency/Courage-and provided clarification of some competencies within existing
      domains. CONCLUSIONS: This study validates and further elaborates dimensions of
      competence believed to be important in rural practice. The authors propose these
      domains as a common language and framework for addressing the unique challenges
      and opportunities that training and practicing in a rural setting present.

PMID- 29346701
TI  - Identifying Prevalence and Characteristics of Behavioral Health Education in
      Family Medicine Clerkships: A CERA Study.
AB  - BACKGROUND AND OBJECTIVES: Many patients with behavioral health disorders do not
      seek or receive adequate care for their conditions. Among those that do, most
      will receive care in a primary care setting. To best meet this need, clinicians
      will need to demonstrate proficiency of behavioral health skills and evidence
      based practices. We sought to explore the degree to which these skills are being
      taught in family medicine clerkships. METHODS: The Council of Academic Family
      Medicine's (CAFM) Educational Research Alliance (CERA) 2016 survey of clerkship
      directors (CDs) was sent to 141 CDs at US and Canadian medical schools with a
      required family medicine run course. CDs were asked about the inclusion of
      behavioral health topics, tools, and techniques in the clerkship, as well as
      rating the importance of these items. RESULTS: Eighty-six percent of CDs
      completed the survey. Mood disorders (81.4%) were most frequently taught,
      followed by anxiety disorders (77.8%), substance use disorders (74.4%), and
      impulse control disorders (39.1%). Screening tools and behavioral health
      counseling skills were less commonly taught. CONCLUSIONS: Many behavioral health
      topics are not taught universally to all family medicine clerkship students. Gaps
      exist between what is included in current curriculum and what is recommended by
      the National Clerkship Curriculum for family medicine. These gaps may represent
      challenges for improving the care for patients with behavioral health disorders.

PMID- 29346702
TI  - And an Equitable New Year.

PMID- 29346703
TI  - Pursuing Personal Passion: Learner-Centered Research Mentoring.
AB  - New researchers often face difficulty finding and focusing research questions. I
      describe a new tool for research mentoring, the Pursuing Personal Passion (P3)
      interview, and a systematic approach to help learners organize their curiosity
      and develop researchable questions aligned with their personal and professional
      priorities. The learner-centered P3 research interview parallels the patient
      centered clinical interview. This paper reviews experience with 27 research
      mentees over the years 2009 to 2016, using the P3 approach to identify their
      initial research topics, classify their underlying passions and track the
      evolution into their final research questions. These researchers usually
      identified one of three personal passions that provided lenses to focus their
      research: problem, person, or process. Initial research topics focused on:
      problem (24%, 6), person (48%, 12) and process (28%, 7). Final research questions
      evolved into: problem (20%, 5), person (32%, 8) and process (48%, 12).
      Identification of the underlying passion can lead researchers who start with one
      general topic to develop it into very different research questions. Using this P3
      approach, mentors can help new researchers focus their interests into
      researchable questions, successful studies, and organized programs of
      scholarship.

PMID- 29346704
TI  - Usefulness of live/real time three/four-dimensional transesophageal
      echocardiography in the percutaneous closure of an iatrogenic aorto-right
      ventricular fistula.
AB  - The development of an aorto-right ventricular fistula is a rare complication of
      cardiac surgery. The most common treatment is surgical closure of the fistula,
      but percutaneous closure of the fistula has become an attractive alternative
      option. We present a case of successful utilization of live/real time three/four
      dimensional transoesophageal echocardiography (3/4DTEE) to select the correct
      device size for percutaneous closure of an adult patient presenting with an aorto
      right ventricular (AO-RV) fistula following aortic valve replacement. To the best
      of our knowledge, this is the first case in which 3/4DTEE was used to select the
      device size and guide percutaneous closure of an iatrogenic AO-RV fistula.

PMID- 29346705
TI  - Effect of dys-1 mutation on gene expression profile in space-flown Caenorhabditis
      elegans.
AB  - INTRODUCTION: Dystrophin-like dys-1 gene expression increases in the body wall
      muscles of Caenorhabditis elegans after spaceflight (SF). Here we used a dys
      1(cx18) mutant to analyze the molecular adaptive responses of C. elegans to SF.
      METHODS: DNA microarrays were performed to identify differentially expressed
      genes between wild-type (WT) and dys-1 mutant worms after SF. We performed Gene
      Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses, predicted
      human diseases, and screened out key genes for human muscle diseases with
      NextBio. RESULTS: Gene expression was less affected by SF in the dys-1 mutant
      than in the WT worms. The dys-1 mutation influenced neuromuscular gene expression
      (neuropeptide genes, muscle-related genes, and dystrophin-related genes) under SF
      conditions, among which 15 genes were specifically regulated by dys-1. NextBio
      analysis predicted that cdka-1, lev-11, unc-27, and unc-94 genes might play
      critical roles in muscle atrophy. DISCUSSION: dys-1 Potentially regulates the
      neuromuscular system in space. Muscle Nerve, 2018.

PMID- 29346706
TI  - Anti-3-hydroxy-3-methylglutaryl-coenzyme a reductase autoantibody-positive
      necrotizing autoimmune myopathy with dermatomyositis-like eruption.

PMID- 29346707
TI  - Tuning the High-Temperature Wetting Behavior of Metals toward Ultrafine
      Nanoparticles.
AB  - The interaction between metal nanoparticles (NPs) and their substrate plays a
      critical role in determining the particle morphology, distribution, and
      properties. The pronounced impact of a thin oxide coating on the dispersion of
      metal NPs on a carbon substrate is presented. Al2 O3 -supported Pt NPs are
      compared to the direct synthesis of Pt NPs on bare carbon surfaces. Pt NPs with
      an average size of about 2 nm and a size distribution ranging between 0.5 nm and
      4.0 nm are synthesized on the Al2 O3 coated carbon nanofiber, a significant
      improvement compared to those directly synthesized on a bare carbon surface.
      First-principles modeling verifies the stronger adsorption of Pt clusters on Al2
      O3 than on carbon, which attributes the formation of ultrafine Pt NPs. This
      strategy paves the way towards the rational design of NPs with enhanced
      dispersion and controlled particle size, which are promising in energy storage
      and electrocatalysis.

PMID- 29346708
TI  - Role of comprehension on performance at higher levels of Bloom's taxonomy:
      Findings from assessments of healthcare professional students.
AB  - The first four levels of Bloom's taxonomy were used to create quiz questions
      designed to assess student learning of the gross anatomy, histology, and
      physiology of the gastrointestinal (GI) system. Information on GI histology and
      physiology was presented to separate samples of medical, dental, and podiatry
      students in computer based tutorials where the information from the two
      disciplines was presented either separately or in an integrated fashion. All
      students were taught GI gross anatomy prior to this study by course faculty as
      part of the required curriculum of their respective program. Student responses to
      the quiz questions were analyzed to assess both the validity of Bloom's
      cumulative hierarchy and the effectiveness of an integrated curriculum. No
      statistically significant differences were found between quiz scores from
      students who received the integrated tutorial and from those who received the
      separate tutorials. Multiple regression analyses provided partial support for a
      cumulative hierarchy where scores on the lower levels of Bloom's taxonomy
      predicted scores on higher levels. Notably, in the majority of regression
      analyses, the comprehension score was the key foundational predictor for
      application and analysis scores. This study supports the suggestion that
      educators increase the number of comprehension level questions, even at the
      expense of knowledge level questions, in course assessments both to evaluate
      lower order cognitive skills and also as a predictor of success on questions
      requiring application and analysis levels of the higher order cognitive skills of
      Bloom's taxonomy. Anat Sci Educ 11: 433-444. (c) 2018 American Association of
      Anatomists.

PMID- 29346709
TI  - Rating the quality of a body of evidence on the effectiveness of health and
      social interventions: A systematic review and mapping of evidence domains.
AB  - INTRODUCTION: Rating the quality of a body of evidence is an increasingly common
      component of research syntheses on intervention effectiveness. This study sought
      to identify and examine existing systems for rating the quality of a body of
      evidence on the effectiveness of health and social interventions. METHODS: We
      used a multicomponent search strategy to search for full-length reports of
      systems for rating the quality of a body of evidence on the effectiveness of
      health and social interventions published in English from 1995 onward. Two
      independent reviewers extracted data from each eligible system on the evidence
      domains included, as well as the development and dissemination processes for each
      system. RESULTS: Seventeen systems met our eligibility criteria. Across systems,
      we identified 13 discrete evidence domains: study design, study execution,
      consistency, measures of precision, directness, publication bias, magnitude of
      effect, dose-response, plausible confounding, analogy, robustness, applicability,
      and coherence. We found little reporting of rigorous procedures in the
      development and dissemination of evidence rating systems. CONCLUSION: We
      identified 17 systems for rating the quality of a body of evidence on
      intervention effectiveness across health and social policy. Existing systems vary
      greatly in the domains they include and how they operationalize domains, and most
      have important limitations in their development and dissemination. The construct
      of the quality of the body of evidence was defined in a few systems largely
      extending the Grading of Recommendations Assessment, Development, and Evaluation
      approach. Grading of Recommendations Assessment, Development, and Evaluation was
      found to be unique in its comprehensive guidance, rigorous development, and
      dissemination strategy.

PMID- 29346710
TI  - An extensive caseous calcification of the mitral annulus complicated with severe
      mitral regurgitation.
AB  - Caseous calcification of the mitral annulus (CCMA) is considered a rare variant
      of mitral annular calcification (MAC) due to caseous transformation of the inner
      material and prevalence of CCMA, about 0.63% of all MAC cases and 0.06%-0.07% of
      the population. The precise pathophysiology of CCMA is still unknown. It is a
      chronic degenerative disorder common in the elderly, particularly in women.
      Caseous calcification of the mitral annulus (CCMA) is a soft peri-annular
      extensive calcification, resembling cardiac tumors, abscesses, vegetation, or
      calcified thrombus, which is composed of an admixture of calcium, fatty acids,
      and cholesterol with a toothpaste-like texture. In the characteristic appearance
      on echocardiography, the calcification is a round, large, soft mass with a
      central echo dense area, typically located at the basal area of the posterior
      mitral valve. It usually carries a benign prognosis but rarely may be complicated
      with mitral valve dysfunction (valve stenosis/mitral regurgitation) or systemic
      embolization. The current data suggest conservative medical therapy and clinical
      follow-up for management of CCMA unless there is a need of cardiac surgery for
      severe mitral stenosis and/or regurgitation. We present a case, complicated with
      severe mitral regurgitation, and need surgical resection of the CCMA because of
      the CCMA-induced symptomatic severe mitral regurgitation despite optimal medical
      therapy. Macroscopic and microscopic examination of caseous material also
      demonstrated the characteristic appearance of CCMA.

PMID- 29346711
TI  - Early assessment of post-surgical outcomes with pre-pectoral breast
      reconstruction: A literature review and meta-analysis.
AB  - BACKGROUND: Pre-pectoral breast reconstruction is an emerging surgical approach.
      This study provides an early assessment of outcomes with the technique. METHODS:
      A comprehensive literature review was performed through searches of PubMed(r)
      /MEDLINE(r) to identify studies on pre-pectoral reconstruction. Patient
      characteristics and outcomes were extracted from studies and pooled. Linear
      relationships between complication rates and patient characteristics with pre
      pectoral reconstruction were analyzed. A meta-analysis compared complication
      rates between pre-pectoral and dual-plane reconstruction. RESULTS: Fourteen
      studies (406 women/654 breasts) were included. The most common complications with
      pre-pectoral reconstruction were flap necrosis (7.8%), seroma (6.7%), capsular
      contracture (5.8%), and explantation (4.6%). No hyperanimation was reported.
      Significant correlation between previous radiation and flap necrosis, post
      operative chemotherapy and infection, hypertension and flap necrosis, diabetes
      and dehiscence, and smoking and explantation were found. A meta-analysis of four
      studies comparing pre-pectoral (135 women/219 breasts) and dual-plane (230/408)
      reconstruction found no significant difference for likelihood of infection (odds
      ratio, 0.46; 95% confidence interval, 0.16-1.30), explantation (0.83; 0.29-2.38),
      necrosis (1.61; 0.77-3.36), seroma (1.88; 0.71-5.02), dehiscence (1.84; 0.68
      4.95), or capsular contracture (0.14; 0.02-1.14). CONCLUSIONS: Complication rates
      are comparable following pre-pectoral and dual-plane reconstruction, indicating
      the pre-pectoral technique may be a feasible option for appropriate patients.

PMID- 29346712
TI  - Synergetic Effects of Prenatal and Postnatal High Sucrose Intake on Glucose
      Tolerance and Hepatic Insulin Resistance in Rat Offspring.
AB  - SCOPE: High sucrose intake during pregnancy is linked to type 2 diabetes mellitus
      and altered insulin resistance. METHODS AND RESULTS: This study attempts to
      ascertain whether prenatal high sucrose intake (20% sucrose) alleviates the
      detrimental effects of high postnatal sugar consumption in the offspring, and the
      molecular mechanisms are investigated using a rat model. High prenatal sucrose
      exposure increases the body weight of the offspring at 1-3 weeks of age. Exposure
      to both prenatal and postnatal high sucrose increases glucose tolerance in the 4
      month-old adult offspring compared with offspring receiving other treatments.
      Postnatal high sucrose exposure suppresses food intake but increases the total
      daily caloric and fluid intake. Both fasting blood glucose and plasma
      triglyceride levels are increased, but the fasting insulin level is unaffected.
      Prenatal high sucrose intake enlarges pancreatic islet area; however, prenatal
      plus-postnatal high sucrose exposure induces smaller pancreatic islets. IRS
      1(S612) protein phosphorylation is significantly increased, and the GSK-3beta
      (S9) phosphorylation level is reduced. CONCLUSION: Both prenatal and prenatal
      plus-postnatal high sucrose exposure substantially affect biological functions
      related to insulin homeostasis. IRS-1(S612) protein phosphorylation appears to be
      a part of the molecular mechanism underlying these effects. These results add to
      the understanding of how high sucrose intake contributes to insulin resistance
      and diabetes pathogenesis and how postnatal nutrition and lifestyle may mitigate
      detrimental prenatal exposures.

PMID- 29346713
TI  - Spark-generated microbubble cell sorter for microfluidic flow cytometry.
AB  - High-speed and accurate cell sorting is of great significance for cell analysis
      regarding both bioresearch and clinical application. Different from the jet-in
      air sorting of commercial flow cytometers, sorting in fully enclosed and disposal
      microfluidic chips can avoid aerosols and crosscontamination, thus contributing
      to the improvement of biosafety and test accuracy. However, current microfluidic
      sorters usually require complicated structures, or otherwise cannot attain high
      throughput. In this article, a sorting mechanism for microfluidics is proposed
      for the first time based on the jet flow induced by the spark-generated
      cavitation microbubble that can be easily realized by a pair of electrodes. The
      sorter was integrated into a microfluidic chip based on three-dimensional (3D)
      hydrodynamic focusing and a binary optical element (BOE) for laser illumination.
      Besides, several aspects of the sorting mechanism were studied to optimize the
      device. It achieved a switching time of 250 MUs at the sample flow velocity of 5
      m/s and performed the continuous operation at 200 Hz. Both the stability of
      fluorescence signals and the viability of cells were basically maintained. To
      conclude, this work explores a new on-chip sorting mechanism which possesses the
      merits of simple structure, easy control, and fast switching. (c) 2018
      International Society for Advancement of Cytometry.

PMID- 29346714
TI  - "Vascular profiles" of regenerative and dysplastic nodules.

PMID- 29346715
TI  - Duchenne muscular dystrophy caused by a novel deep intronic DMD mutation.

PMID- 29346716
TI  - Neuropeptide AF Induces Piecemeal Degranulation in Murine Mucosal Mast Cells: A
      New Mediator in Neuro-Immune Communication in the Intestinal Lamina Propria?
AB  - Neuropeptides AF (NPAF), FF (NPFF) and SF (NPSF) are RFamide neuropeptides known
      to be widely expressed in the mammalian central nervous system, where they
      fulfill a wide range of functions with pain modulation being the most prominent
      one. Recent evidence indicates that RFamides act as mediators in mast cell
      sensory nerve communications related to allergic disease. Previous work by our
      group has shown that the expression levels of some members of the Mas-related
      gene receptor (Mrgpr) family in both enteric neurons and mucosal mast cells
      change during intestinal inflammation. The Mrgpr subtypes C11 and A4 can be
      activated by NPAF, while A1 and C11 are triggered by NPFF. The aim of the present
      study was to investigate whether RFamides of the NPFF group are expressed in the
      gastrointestinal tract and to identify possible targets and receptors that might
      be involved in RFamide-associated mast cell modulation. To this end, the
      expression and distribution patterns of NPFF/AF receptors and the NPFF precursor
      protein were determined in bone marrow-derived mucosal mast cells (BMMCs) by
      immunocytochemistry and (RT-) PCR. BMMCs were found to express MrgprA4 and A1,
      and functional analysis of the effects of NPAF by means of a beta-hexosaminidase
      assay, mMCP-1 ELISA, electron microscopy and live cell calcium imaging revealed a
      piecemeal degranulation induced by NPAF. However, knock-out of MrgprA4 and A1 did
      not reduce the effect of NPAF, indicating that the BMMC response to NPAF was
      receptor independent. ProNPFF was expressed in neurons and BMMCs, suggesting that
      both cell types are potential sources of NPAF in situ. Our results show that the
      RFamide NPAF can be considered as a novel modulator of BMMC activity in the neuro
      immune communication in the gastrointestinal tract, although the exact signaling
      pathway remains to be elucidated. Anat Rec, 00:000-000, 2018. (c) 2018 Wiley
      Periodicals, Inc. Anat Rec, 301:1103-1114, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 29346718
TI  - EDITORIAL.

PMID- 29346717
TI  - Anterior cruciate ligament tear induces a sustained loss of muscle fiber force
      production.
AB  - INTRODUCTION: Patients with anterior cruciate ligament (ACL) tears have
      persistent quadriceps strength deficits that are thought to be due to altered
      neurophysiological function. Our goal was to determine the changes in muscle
      fiber contractility independent of the ability of motor neurons to activate
      fibers. METHODS: We obtained quadriceps biopsies of patients undergoing ACL
      reconstruction, and additional biopsies 1, 2, and 6 months after surgery. Muscles
      fiber contractility was assessed in vitro, along with whole muscle strength
      testing. RESULTS: Compared with controls, patients had a 30% reduction in
      normalized muscle fiber force at the time of surgery. One month later, the force
      deficit was 41%, and at 6 months the deficit was 23%. Whole muscle strength
      testing demonstrated similar trends. DISCUSSION: While neurophysiological
      dysfunction contributes to whole muscle weakness, there is also a reduction in
      the force generating capacity of individual muscle cells independent of alpha
      motor neuron activation. Muscle Nerve, 2018.

PMID- 29346719
TI  - A Tunable Molten-Salt Route for Scalable Synthesis of Ultrathin Amorphous Carbon
      Nanosheets as High-Performance Anode Materials for Lithium-Ion Batteries.
AB  - Amorphous carbon is regarded as a promising alternative to commercial graphite as
      the lithium-ion battery anode due to its capability to reversibly store more
      lithium ions. However, the structural disorder with a large number of defects can
      lead to low electrical conductivity of the amorphous carbon, thus limiting its
      application for high power output. Herein, ultrathin amorphous carbon nanosheets
      were prepared from petroleum asphalt through tuning the carbonization temperature
      in a molten-salt medium. The amorphous nanostructure with expanded carbon
      interlayer spacing can provide substantial active sites for lithium storage,
      while the two-dimensional (2D) morphology can facilitate fast electrical
      conductivity. As a result, the electrodes deliver a high reversible capacity,
      outstanding rate capability, and superior cycling performance (579 and 396 mAh g
      1 at 2 and 5 A g-1 after 900 cycles). Furthermore, full cells consisting of the
      carbon anodes coupled with LiMn2O4 cathodes exhibit high specific capacity (608
      mAh g-1 at 50 mA g-1) and impressive cycling stability with slow capacity loss
      (0.16% per cycle at 200 mA g-1). The present study not only paves the way for
      industrial-scale synthesis of advanced carbon materials for lithium-ion batteries
      but also deepens the fundamental understanding of the intrinsic mechanism of the
      molten-salt method.

PMID- 29346720
TI  - Nanoscale Control of Molecular Self-Assembly Induced by Plasmonic Hot-Electron
      Dynamics.
AB  - Self-assembly processes allow designing and creating complex nanostructures using
      molecules as building blocks and surfaces as scaffolds. This autonomous driven
      construction is possible due to a complex thermodynamic balance of molecule
      surface interactions. As such, nanoscale guidance and control over this process
      is hard to achieve. Here we use the highly localized light-to-chemical-energy
      conversion of plasmonic materials to spatially cleave Au-S bonds on predetermined
      locations within a single nanoparticle, enabling a high degree of control over
      this archetypal system for molecular self-assembly. Our method offers nanoscale
      precision and high-throughput light-induced tailoring of the surface chemistry of
      individual and packed nanosized metallic structures by simply varying wavelength
      and polarization of the incident light. Assisted by single-molecule super
      resolution fluorescence microscopy, we image, quantify, and shed light onto the
      plasmon-induced desorption mechanism. Our results point toward localized
      distribution of hot electrons, contrary to uniformly distributed lattice heating,
      as the mechanism inducing Au-S bond breaking. We demonstrate that plasmon-induced
      photodesorption enables subdiffraction and even subparticle multiplexing.
      Finally, we explore possible routes to further exploit these concepts for the
      selective positioning of nanomaterials and the sorting and purification of
      colloidal nanoparticles.

PMID- 29346721
TI  - Emulsion Electrospinning of Polytetrafluoroethylene (PTFE) Nanofibrous Membranes
      for High-Performance Triboelectric Nanogenerators.
AB  - Electrospinning is a simple, versatile technique for fabricating fibrous
      nanomaterials with the desirable features of extremely high porosities and large
      surface areas. Using emulsion electrospinning, polytetrafluoroethylene/polyethene
      oxide (PTFE/PEO) membranes were fabricated, followed by a sintering process to
      obtain pure PTFE fibrous membranes, which were further utilized against a
      polyamide 6 (PA6) membrane for vertical contact-mode triboelectric nanogenerators
      (TENGs). Electrostatic force microscopy (EFM) measurements of the sintered
      electrospun PTFE membranes revealed the presence of both positive and negative
      surface charges owing to the transfer of positive charge from PEO which was
      further corroborated by FTIR measurements. To enhance the ensuing triboelectric
      surface charge, a facile negative charge-injection process was carried out onto
      the electrospun (ES) PTFE subsequently. The fabricated TENG gave a stabilized
      peak-to-peak open-circuit voltage (Voc) of up to ~900 V, a short-circuit current
      density (Jsc) of ~20 mA m-2, and a corresponding charge density of ~149 MUC m-2,
      which are ~12, 14, and 11 times higher than the corresponding values prior to the
      ion-injection treatment. This increase in the surface charge density is caused by
      the inversion of positive surface charges with the simultaneous increase in the
      negative surface charge on the PTFE surface, which was confirmed by using EFM
      measurements. The negative charge injection led to an enhanced power output
      density of ~9 W m-2 with high stability as confirmed from the continuous
      operation of the ion-injected PTFE/PA6 TENG for 30 000 operation cycles, without
      any significant reduction in the output. The work thus introduces a relatively
      simple, cost-effective, and environmentally friendly technique for fabricating
      fibrous fluoropolymer polymer membranes with high thermal/chemical resistance in
      TENG field and a direct ion-injection method which is able to dramatically
      improve the surface negative charge density of the PTFE fibrous membranes.

PMID- 29346722
TI  - Layer-by-Layer Epitaxial Growth of Defect-Engineered Strontium Cobaltites.
AB  - Control over structure and composition of (ABO3) perovskite oxides offers
      exciting opportunities since these materials possess unique, tunable properties.
      Perovskite oxides with cobalt B-site cations are particularly promising, as the
      range of the cation's stable oxidation states leads to many possible structural
      frameworks. Here, we report growth of strontium cobalt oxide thin films by
      molecular beam epitaxy, and conditions necessary to stabilize different defect
      concentration phases. In situ X-ray scattering is used to monitor structural
      evolution during growth, while in situ X-ray absorption near-edge spectroscopy is
      used to probe oxidation state and measure changes to oxygen vacancy concentration
      as a function of film thickness. Experimental results are compared to kinetically
      limited thermodynamic predictions, in particular, solute trapping, with
      semiquantitative agreement. Agreement between observations of dependence of
      cobaltite phase on oxidation activity and deposition rate, and predictions
      indicates that a combined experimental/theoretical approach is key to
      understanding phase behavior in the strontium cobalt oxide system.

PMID- 29346723
TI  - Shear-Induced Brittle Failure along Grain Boundaries in Boron Carbide.
AB  - The role that grain boundaries (GBs) can play on mechanical properties has been
      studied extensively for metals and alloys. However, for covalent solids such as
      boron carbide (B4C), the role of GB on the inelastic response to applied stresses
      is not well established. We consider here the unusual ceramic, boron carbide
      (B4C), which is very hard and lightweight but exhibits brittle impact behavior.
      We used quantum mechanics (QM) simulations to examine the mechanical response in
      atomistic structures that model GBs in B4C under pure shear and also with biaxial
      shear deformation that mimics indentation stress conditions. We carried out these
      studies for two simple GB models including also the effect of adding Fe atoms
      (possible sintering aid and/or impurity) to the GB. We found that the critical
      shear stresses of these GB models are much lower than that for crystalline and
      twinned B4C. The two GB models lead to different interfacial energies. The higher
      interfacial energy at the GB only slightly decreases the critical shear stress
      but dramatically increases the critical failure strain. Doping the GB with Fe
      decreases the critical shear stress of at the boundary by 14% under pure shear
      deformation. In all GBs studied here, failure arises from deconstructing the
      icosahedra within the GB region under shear deformation. We find that Fe dopant
      interacts with icosahedra at the GB to facilitate this deconstruction of
      icosahedra. These results provide significant insight into designing
      polycrystalline B4C with improved strength and ductility.

PMID- 29346724
TI  - Structural and Biophysical Characterization of Human EXTL3: Domain Organization,
      Glycosylation, and Solution Structure.
AB  - Heparan sulfate proteoglycans are proteins substituted with one or more heparan
      sulfate (HS) polysaccharides, found in abundance at cell surfaces. HS chains
      influence the activity of many biologically important molecules involved in
      cellular communication and signaling. The exostosin (EXT) proteins are
      glycosyltransferases in the Golgi apparatus that assemble HS chains on HSPGs. The
      EXTL3 enzyme mainly works as an initiator in HS biosynthesis. In this work, human
      lumenal N-glycosylated EXTL3 (EXTL3DeltaN) was cloned, expressed in human
      embryonic kidney cells, and purified. Various biophysical and biochemical
      approaches were then employed to elucidate the N-glycosylation sites and the
      function of their attached N-glycans. Furthermore, the stability and conformation
      of the purified EXTL3DeltaN protein in solution have been analyzed. Our data show
      that EXTL3DeltaN has N-glycans at least at two positions, Asn290 and Asn592,
      which seem to be critical for proper protein folding and/or release. EXTL3DeltaN
      is quite stable, as high temperature (~59  degrees C) was required for
      denaturation. Deconvolution of the EXTL3DeltaN far-UV CD spectrum revealed a
      substantial fraction of beta sheets (25%) with a minor proportion of alpha
      helices (14%) in the secondary structure. Solution small-angle X-ray scattering
      and dynamic light scattering revealed an extended structure suggestive of a
      dimeric arrangement and consisting of two distinct regions, narrow and broad,
      respectively. This is consistent with bioinformatics analyses suggesting a 3
      domain structure with two glycosyltransferase domains and a coiled-coil domain.

PMID- 29346725
TI  - Rapid Chemical Vapor Infiltration of Silicon Carbide Minicomposites at
      Atmospheric Pressure.
AB  - The chemical vapor infiltration technique is one of the most popular for the
      fabrication of the matrix portion of a ceramic matrix composite. This work
      focuses on tailoring an atmospheric pressure deposition of silicon carbide onto
      carbon fiber tows using the methyltrichlorosilane (CH3SiCl3) and H2 deposition
      system at atmospheric pressure to create minicomposites faster than low pressure
      systems. Adjustment of the flow rate of H2 bubbled through CH3SiCl3 will improve
      the uniformity of the deposition as well as infiltrate the substrate more
      completely as the flow rate is decreased. Low pressure depositions conducted at
      50 Torr deposit SiC at a rate of approximately 200 nm*h-1, while the atmospheric
      pressure system presented has a deposition rate ranging from 750 nm*h-1 to 3.88
      MUm*h-1. The minicomposites fabricated in this study had approximate total
      porosities of 3 and 6% for 10 and 25 SCCM infiltrations, respectively.

PMID- 29346726
TI  - The Effect of Dielectric Environment on Doping Efficiency in Colloidal PbSe
      Nanostructures.
AB  - Doping, as a central strategy to control free carrier type and concentration in
      semiconductor materials, suffers from low efficiency at the nanoscale, especially
      in systems having high permittivity (epsilon) and large Bohr radii, such as lead
      chalcogenide nanocrystals (NCs) and nanowires (NWs). Here, we study dielectric
      confinement effects on the doping efficiency of lead chalcogenides nanostructures
      by integrating PbSe NWs in the platform of field effect transistors (FETs).
      Elemental Pb or In or elemental Se is deposited by thermal evaporation to
      remotely n- or p-dope the NWs. Polymeric and oxide materials of varying epsilon
      are subsequently deposited to control the dielectric environment surrounding the
      NWs. Analyzing the device characteristics, we extract the change of carrier
      concentration introduced by tailoring the dielectric environment. The calculated
      doping efficiency for n-type (Pb/In) and p-type (Se) dopants increases as the
      epsilon of the surrounding medium increases. Using a high-epsilon material, such
      as HfO2 for encapsulation, the doping efficiency can be enhanced by >10-fold. A
      theoretical model is built to describe the doping efficiency in PbSe NWs embedded
      in different dielectric environments, which agrees with our experimental data for
      both NW array and single NW devices. As dielectric confinement affects all low
      dimensional materials, engineering the dielectric environment is a promising
      general approach to enhance doping concentrations, without introducing excess
      impurities that may scatter carriers, and is suitable for various device
      applications.

PMID- 29346727
TI  - Bioinspired Pressure-Tolerant Asymmetric Slippery Surface for Continuous Self
      Transport of Gas Bubbles in Aqueous Environment.
AB  - Biosurfaces with geometry-gradient structures or special wettabilities
      demonstrate intriguing performance in manipulating the behaviors of versatile
      fluids. By mimicking natural species, that is, the cactus spine with a shape
      gradient morphology and the Picher plant with a lubricated inner surface, we have
      successfully prepared an asymmetric slippery surface by following the processes
      of CO2-laser cutting, superhydrophobic modification, and the fluorinert infusion.
      The asymmetric morphology will cause the deformation of gas bubbles and
      subsequently engender an asymmetric driven force on them. Due to the infusion of
      fluorinert, which has a low surface energy (~16 mN/m, 25  degrees C) and an easy
      fluidic property (~0.75 cP, 25  degrees C), the slippery surface demonstrates
      high adhesive force (~300 MUN) but low friction force on the gas bubbles. Under
      the cooperation of the asymmetric morphology and fluorinert infused surface, the
      fabricated asymmetric slippery surface is applicable to the directional and
      continuous bubble delivery in an aqueous environment. More importantly, due to
      the hard-compressed property of fluorinert, the asymmetric slippery surface is
      facilitated with distinguished bubble transport capability even in a pressurized
      environment (~0.65 MPa), showing its feasibility in practical industrial
      production. In addition, asymmetric slippery surfaces with a snowflake-like
      structure and a star-shaped structure were successfully fabricated for the real
      world applications, both of which illustrated reliable performances in the
      continuous generation, directional transportation, and efficient collection of
      CO2 and H2 microbubbles.

PMID- 29346728
TI  - Design and Assembly of Chiral Coordination Cages for Asymmetric Sequential
      Reactions.
AB  - Supramolecular nanoreactors featuring multiple catalytically active sites are of
      great importance, especially for asymmetric catalysis, and are yet challenging to
      construct. Here we report the design and assembly of five chiral single- and
      mixed-linker tetrahedral coordination cages using six dicarboxylate ligands
      derived-from enantiopure Mn(salen), Cr(salen) and/or Fe(salen) as linear linkers
      and four Cp3Zr3 clusters as three-connected vertices. The formation of these
      cages was confirmed by a variety of techniques including single-crystal and
      powder X-ray diffraction, inductively coupled plasma optical emission
      spectrometer, quadrupole-time-of-flight mass spectrometry and energy dispersive X
      ray spectrometry. The cages feature a nanoscale hydrophobic cavity decorated with
      the same or different catalytically active sites, and the mixed-linker cage
      bearing Mn(salen) and Cr(salen) species is shown to be an efficient
      supramolecular catalyst for sequential asymmetric alkene epoxidation/epoxide ring
      opening reactions with up to 99.9% ee. The cage catalyst demonstrates improved
      activity and enantioselectivity over the free catalysts owing to stabilization of
      catalytically active metallosalen units and concentration of reactants within the
      cavity. Manipulation of catalytic organic linkers in cages can control the
      activities and selectivities, which may provide new opportunities for the design
      and assembly of novel functional supramolecular architectures.

PMID- 29346729
TI  - Electronic Interactions in Iminophosphorane Superbase Complexes with Carbon
      Dioxide.
AB  - Iminophosphoranes or phosphazenes are an important class of compounds with
      increasing use in synthetic organic chemistry as neutral organic superbases
      exhibiting low nucleophilicity. Their electronic structure and therefore their
      properties strongly depend on substitution, but there have been very few
      theoretical studies devoted to this topic, and more specifically to the formation
      of electron donor-acceptor complexes of iminophosphoranes with electrophiles. In
      this work, we have investigated the interaction with carbon dioxide at different
      ab initio levels. Carbon dioxide usually behaves as a Lewis acid and the reaction
      with iminiphosphoranes has been described as a nonconventional aza-Wittig process
      leading to isocyanates. The reaction can be conducted in supercritical CO2
      conditions (carbon dioxide acts as both solvent and reactant), which is a
      promising strategy in the context of green chemistry. Our calculations have been
      carried out at the CCSD(T)/aug-cc-pVTZ//MP2/aug-cc-pVTZ level for model systems
      and at the M06-2X/6-611+G(d,p) level for a larger species used in experiments.
      The electronic interactions and the interaction energies are analyzed and
      discussed in detail using the natural bond orbital method. Proton affinities and
      gas-phase basicities are provided as well.

PMID- 29346731
TI  - Direct Polymerization of the Arsenic Drug PENAO to Obtain Nanoparticles with High
      Thiol-Reactivity and Anti-Cancer Efficiency.
AB  - PENAO (4-(N-(S-penicillaminylacetyl)amino) phenylarsonous acid), which is a
      mitochondria inhibitor that reacts with adenine nucleotide translocator (ANT), is
      currently being trialed in patients with solid tumors. To increase the stability
      of the drug, the formation of nanoparticles has been proposed. Herein, the direct
      synthesis of polymeric micelles based on the anticancer drug PENAO is presented.
      PENAO is readily available for amidation reaction to form PENAO MA (4-(N-(S
      penicillaminylacetyl) amino) phenylarsonous acid methacrylamide) which undergoes
      RAFT (reversible addition-fragmentation chain transfer) polymerization with
      poly(ethylene glycol methyl ether methacrylate) as comonomer and poly(methyl
      methacrylate) (pMMA) as chain transfer agent, resulting in p(MMA)-b-p(PEG-co
      PENAO) block copolymers with 3-15 wt % of PENAO MA. The different block
      copolymers self-assembled into micelle structures, varying in size and stability
      (Dh = 84-234 nm, cmc = 0.5-82 MUg mol-1) depending on the hydrophilic to
      hydrophobic ratio of the polymer blocks and the amount of drug in the corona of
      the particle. The more stable micelle structures were investigated toward 143B
      human osteosarcoma cells, showing an enhanced cytotoxicity and cellular uptake
      compared to the free drug PENAO (IC50 (PENAO) = 2.7 +/- 0.3 MUM; IC50 (micelle
      M4) = 0.8 +/- 0.02 MUM). Furthermore, PENAOs arsonous acid residue remains active
      when incorporated into a polymer matrix and conjugates to small mono and closely
      spaced dithiols and is able to actively target the mitochondria, which is PENAO's
      main target to introduce growth inhibition in cancer cells. As a result, no
      cleavable linker between drug and polymer was necessary for the delivery of PENAO
      to osteosarcoma cells. These findings provide a rationale for in vivo studies of
      micelle M4 versus PENAO in an osteosarcoma animal model.

PMID- 29346732
TI  - Microscopic Theory of Coupled Slow Activated Dynamics in Glass-Forming Binary
      Mixtures.
AB  - The Elastically Collective Nonlinear Langevin Equation theory for one-component
      viscous liquids and suspensions is generalized to treat coupled slow activated
      relaxation and diffusion in glass-forming binary sphere mixtures of any
      composition, size ratio, and interparticle interactions. A trajectory-level
      dynamical coupling parameter concept is introduced to construct two coupled
      dynamic free energy functions for the smaller penetrant and larger matrix
      particle. A two-step dynamical picture is proposed where the first-step process
      involves matrix-facilitated penetrant hopping quantified in a self-consistent
      manner based on a temporal coincidence condition. After penetrants dynamically
      equilibrate, the effectively one-component matrix particle dynamics is controlled
      by a new dynamic free energy (second-step process). Depending on the time scales
      associated with the first- and second-step processes, as well as the extent of
      matrix-correlated facilitation, distinct physical scenarios are predicted. The
      theory is implemented for purely hard-core interactions, and addresses the glass
      transition based on variable kinetic criteria, penetrant-matrix coupled activated
      relaxation, self-diffusion of both species, dynamic fragility, and shear
      elasticity. Testable predictions are made. Motivated by the analytic ultralocal
      limit idea derived for pure hard sphere fluids, we identify structure
      thermodynamics-dynamics relationships. As a case study for molecule-polymer
      thermal mixtures, the chemically matched fully miscible polystyrene-toluene
      system is quantitatively studied based on a predictive mapping scheme. The
      resulting no-adjustable-parameter results for toluene diffusivity and the mixture
      glass transition temperature are in good agreement with experiment. The theory
      provides a foundation to treat diverse dynamical problems in glass-forming
      mixtures, including suspensions of colloids and nanoparticles, polymer-molecule
      liquids, and polymer nanocomposites.

PMID- 29346730
TI  - Two-Dimensional Spectroscopy Is Being Used to Address Core Scientific Questions
      in Biology and Materials Science.
AB  - Two-dimensional spectroscopy is a powerful tool for extracting structural and
      dynamic information from a wide range of chemical systems. We provide a brief
      overview of the ways in which two-dimensional visible and infrared spectroscopies
      are being applied to elucidate fundamental details of important processes in
      biological and materials science. The topics covered include amyloid proteins,
      photosynthetic complexes, ion channels, photovoltaics, batteries, as well as a
      variety of promising new methods in two-dimensional spectroscopy.

PMID- 29346733
TI  - Synthesis and Structure-Activity Relationship (SAR) Studies of Novel
      Pyrazolopyridine Derivatives as Inhibitors of Enterovirus Replication.
AB  - A series of novel pyrazolopyridine compounds have been designed and prepared by a
      general synthetic route. Their activities against the replication of poliovirus
      1, EV-A71, and CV-B3 enteroviruses were evaluated. The comprehensive
      understanding of the structure-activity relationship was obtained by utilizing
      the variation of four positions, namely, N1, C6, C4, and linker unit. From the
      screened analogues, the inhibitors with the highest selectivity indices at 50%
      inhibition of viral replication (SI50) were those with isopropyl at the N1
      position and thiophenyl-2-yl unit at C6 position. Furthermore, the C4 position
      offered the greatest potential for improvement because many different N-aryl
      groups had better antiviral activities and compatibilities than the lead compound
      JX001. For example, JX040 with a 2-pyridyl group was the analogue with the most
      potent activity against non-polio enteroviruses, and JX025, possessing a 3
      sulfamoylphenyl moiety, had the best activity against polioviruses. In addition,
      analogue JX037, possessing a novel pyrazolopyridine heterocycle, was also shown
      to have good antienteroviral activity, which further enlarges the compound space
      for antienteroviral drug design.

PMID- 29346734
TI  - Fluctuation Effects on the Brush Structure of Mixed Brush Nanoparticles in
      Solution.
AB  - A potentially attractive way to control nanoparticle assembly is to graft one or
      more polymers on the nanoparticle, to control the nanoparticle-nanoparticle
      interactions. When two immiscible polymers are grafted on the nanoparticle, they
      can microphase separate to form domains at the nanoparticle surface. Here, we
      computationally investigate the phase behavior of such binary mixed brush
      nanoparticles in solution, across a large and experimentally relevant parameter
      space. Specifically, we calculate the mean-field phase diagram, assuming uniform
      grafting of the two polymers, as a function of the nanoparticle size relative to
      the length of the grafted chains, the grafting density, the enthalpic repulsion
      between the grafted chains, and the solvent quality. We find a variety of phases
      including a Janus phase and phases with varying numbers of striped domains. Using
      a nonuniform, random distribution of grafting sites on the nanoparticle instead
      of the uniform distribution leads to the development of defects in the mixed
      brush structures. Introducing fluctuations as well leads to increasingly
      defective structures for the striped phases. However, we find that the simple
      Janus phase is preserved in all calculations, even with the introduction of
      nonuniform grafting and fluctuations. We conclude that the formation of the Janus
      phase is more realistic experimentally than is the formation of defect-free
      multivalent mixed brush nanoparticles.

PMID- 29346735
TI  - Mechanisms of Modulation of Calcium Phosphate Pathological Mineralization by
      Mobile and Immobile Small-Molecule Inhibitors.
AB  - Potential pathways for inhibiting crystal growth are via either disrupting local
      microenvironments surrounding crystal-solution interfaces or physically blocking
      solute molecule attachment. However, the actual mode of inhibition may be more
      complicated due to the characteristic time scale for the inhibitor adsorption and
      relaxation to a well-bound state at crystal surfaces. Here we demonstrate the
      role of citrate (CA) and hydroxycitrate (HCA) in brushite (DCPD, CaHPO4.2H2O)
      crystallization over a broad range of both inhibitor concentrations and
      supersaturations by in situ atomic force microscopy (AFM). We observed that both
      inhibitors exhibit two distinct actions: control of surface crystallization by
      the decrease of step density at high supersaturations and the decrease of the
      [100]Cc step velocity at high inhibitor concentration and low supersaturation.
      The switching of the two distinct modes depends on the terrace lifetime, and the
      slow kinetics along the [100]Cc step direction provides specific sites for the
      newly formed dislocations. Molecular modeling shows the strong HCA-crystal
      interaction by molecular recognition, explaining the AFM observations for the
      formation of new steps and surface dissolution along the [101]Cc direction due to
      the introduction of strong localized strain in the crystal lattice. These direct
      observations highlight the importance of the inhibitor coverage on mineral
      surfaces, as well as the solution supersaturation in predicting the inhibition
      efficacy, and reveal an improved understanding of inhibition of calcium phosphate
      biomineralization, with clinical implications for the full therapeutic potential
      of small-molecule inhibitors for kidney stone disease.

PMID- 29346736
TI  - Light-Activatable Red Blood Cell Membrane-Camouflaged Dimeric Prodrug
      Nanoparticles for Synergistic Photodynamic/Chemotherapy.
AB  - Biomimetic approach offers numerous opportunities to design therapeutic platforms
      with enhanced antitumor performance and biocompatibility. Herein we report red
      blood cell membrane-camouflaged nanoparticles (RBC(M(TPC-PTX))) for synergistic
      chemo- and photodynamic therapy (PDT). Specifically, the inner core is mainly
      constructed by reactive oxygen species (ROS)-responsive PTX dimer (PTX2-TK) and
      photosensitizer 5,10,15,20-tetraphenylchlorin (TPC). In vitro experiments show
      that the prepared RBC(M(TPC-PTX)) is readily taken up into endosomes. Under
      appropriate light irradiation, the TPC can generate ROS, not only for PDT but
      also for triggering PTX2-TK cleavage and on-demand PTX release for chemotherapy.
      In vivo results show that the coating of RBC membrane prolongs blood circulation
      and improves tumor accumulation. The combination of chemo- and photodynamic
      therapy enhances anticancer therapeutic activity, and light-triggered drug
      release reduces systematic toxicity. All these characteristics render the
      described technology extremely promising for cancer treatment.

PMID- 29346737
TI  - Quantitative and Qualitative Assessment of the Relative Arterial Contributions to
      the Calcaneus.
AB  - BACKGROUND: The purpose of this study was to quantitatively and qualitatively
      assess relative arterial contributions to the calcaneus. METHOD: Fourteen
      cadaveric ankle pairs were used. In each specimen, the posterior tibial artery,
      peroneal artery, and anterior tibial artery were cannulated and used for contrast
      enhanced magnetic resonance imaging (MRI) and computed tomography (CT).
      Quantitative MRI analysis of the pre- and postcontrast MRI scans facilitated
      assessment of relative arterial contributions. In addition, postcontrast MRIs
      were used to measure all perfused arterial entry points and scaled to a 3
      dimensional calcaneus model. Contrast-enhanced CT imaging was assessed to further
      delineate the extraosseous arterial course. Two pairs underwent infusion of
      diluted BaSO4 through a constant-pressure pump using extended infusion duration.
      RESULTS: Quantitative MRI findings indicated the peroneal artery provided 52.6%
      of the calcaneal arterial supply, 31.6% from the posterior tibial artery, and
      15.8% from the anterior tibial artery. The cortical entry points were found in
      fairly consistent patterns along calcaneal cortical surfaces. All specimens
      demonstrated intraosseous anastomoses between lateral and medial entry points at
      common locations. CONCLUSIONS: The peroneal artery was found to provide the
      largest calcaneal arterial contribution, followed by the posterior tibial artery
      and anterior tibial artery. A rich anastomotic arterial network was found
      supplying the calcaneus. CLINICAL RELEVANCE: This study provides quantitative and
      qualitative findings of the relative arterial contribution of the calcaneus. This
      knowledge can help expand our understanding of calcaneal vascularization,
      demonstrate the vascular impact of calcaneal fracture and surgery, and facilitate
      future research on the arterial anatomy of the calcaneal soft tissue envelope.

PMID- 29346738
TI  - First Record of Leucocytozoon (Haemosporida: Leucocytozoidae) in Amazonia:
      Evidence for Rarity in Neotropical Lowlands or Lack of Sampling for This Parasite
      Genus?
AB  - Birds harbor an astonishing diversity of haemosporidian parasites belonging to
      the genera Haemoproteus, Leucocytozoon, and Plasmodium. Currently there are more
      than 250 morphologically described avian haemosporidian species and 2,828 unique
      lineages found in virtually all avian clades and zoogeographic regions, except
      for Antarctica. Our report is based on PCR and microscopic screening of 1,302
      individual avian samples from Brazil to detect the underrepresented genus
      Leucocytozoon. This survey primarily focuses on passerine birds collected from
      Amazonia, the Atlantic Rain Forest, and Pantanal. We also summarize studies
      conducted in Brazil that report haemosporidian prevalence using both microscopy
      and molecular tools and present for the first time a record of Leucocytozoon
      infecting an avian host population in Amazonia. Based on our findings, we suggest
      that high average temperatures may be constraining both the distribution and
      diversity of Leucocytozoon in lowland tropical South America.

PMID- 29346739
TI  - The Role of the Diabetes Educator in Diabetes Formulary and Medical Device
      Decisions.
AB  - It is the position of the American Association of Diabetes Educators that
      diabetes educators should be included as expert consultants for formulary
      decisions regarding diabetes medications and medical devices.

PMID- 29346740
TI  - Role of the Diabetes Educator in Inpatient Diabetes Management.
AB  - It is the position of American Association of Diabetes Educators (AADE) that all
      inpatient interdisciplinary teams include a diabetes educator to lead or support
      improvement efforts that affect patients hospitalized with diabetes or
      hyperglycemia. This not only encompasses patient and family education but
      education of interdisciplinary team members and achievement of diabetes-related
      organizational quality metrics and performance outcomes.

PMID- 29346742
TI  - Management of Children With Diabetes in the School Setting.
AB  - Diabetes educators are well positioned to help optimize care of the student with
      diabetes within the school setting.

PMID- 29346743
TI  - Publishing AADE's Position Statements.

PMID- 29346745
TI  - The THIK and Thin of Microglia Dynamics.
AB  - Madry et al. (2018) show that the two-pore potassium channel THIK-1 is tonically
      active in microglia and promotes microglial ramification and surveillance of the
      brain parenchyma. Interestingly, THIK-1 is not essential to damage-induced
      outgrowth of microglial processes but is critical to microglial IL-1beta release.

PMID- 29346744
TI  - 2017 National Standards for Diabetes Self-Management Education and Support.
AB  - Purpose The purpose of this study is to review the literature for Diabetes Self
      Management Education and Support (DSMES) to ensure the National Standards for
      DSMES (Standards) align with current evidence-based practices and utilization
      trends. Methods The 10 Standards were divided among 20 interdisciplinary
      workgroup members. Members searched the current research for diabetes education
      and support, behavioral health, clinical, health care environment, technical,
      reimbursement, and business practice for the strongest evidence that guided the
      Standards revision. Results Diabetes Self-Management Education and Support
      facilitates the knowledge, skills, and ability necessary for diabetes self-care
      as well as activities that assist a person in implementing and sustaining the
      behaviors needed to manage their condition on an ongoing basis. The evidence
      indicates that health care providers and people affected by diabetes are
      embracing technology, and this is having a positive impact of DSMES access,
      utilization, and outcomes. Conclusion Quality DSMES continues to be a critical
      element of care for all people with diabetes. The DSMES services must be
      individualized and guided by the concerns, preferences, and needs of the person
      affected by diabetes. Even with the abundance of evidence supporting the benefits
      of DSMES, it continues to be underutilized, but as with other health care
      services, technology is changing the way DSMES is delivered and utilized with
      positive outcomes.

PMID- 29346746
TI  - Shh-ushing Midline Crossing through Remote Protein Transport.
AB  - Shh contributes to neural circuit formation with different mechanisms. In this
      issue, Peng and colleagues (2018) identify a novel trans-axonal mechanism by
      which Shh derived from contralateral projecting retinal ganglion cells prevents
      midline crossing of Boc-expressing ipsilateral axons at the optic chiasm.

PMID- 29346747
TI  - Sensorimotor Integration for Decision Making: How the Worm Steers.
AB  - Animals' movements actively shape their perception and subsequent decision
      making. In this issue of Neuron, Liu et al. (2018) show how C. elegans nematodes
      steer toward an odorant: a dedicated interneuron class integrates oscillatory
      olfactory signals, generated by head swings, with corollary discharge motor
      signals.

PMID- 29346748
TI  - Spiraling Connectivity of NAc-VTA Circuitry.
AB  - How do nucleus accumbens (NAc) subdivisions shape information flow into distinct
      ventral tegmental area (VTA) subcircuits? Yang et al. (2018) provide insightful
      answers to this question by expanding our knowledge about the circuit
      architecture and function of reciprocal connectivity between NAc and VTA.

PMID- 29346749
TI  - Statistical Challenges in "Big Data" Human Neuroimaging.
AB  - Smith and Nichols discuss "big data" human neuroimaging studies, with very large
      subject numbers and amounts of data. These studies provide great opportunities
      for making new discoveries about the brain but raise many new analytical
      challenges and interpretational risks.

PMID- 29346750
TI  - From Healthcare to Warfare and Reverse: How Should We Regulate Dual-Use
      Neurotechnology?
AB  - Recent advances in military-funded neurotechnology and novel opportunities for
      misusing neurodevices show that the problem of dual use is inherent to
      neuroscience. This paper discusses how the neuroscience community should respond
      to these dilemmas and delineates a neuroscience-specific biosecurity framework.
      This neurosecurity framework involves calibrated regulation, (neuro)ethical
      guidelines, and awareness-raising activities within the scientific community.

PMID- 29346751
TI  - The Brain Compass: A Perspective on How Self-Motion Updates the Head Direction
      Cell Attractor.
AB  - Head direction cells form an internal compass signaling head azimuth orientation
      even without visual landmarks. This property is generated by a neuronal ring
      attractor that is updated using rotation velocity cues. The properties and origin
      of this velocity drive remain, however, unknown. We propose a quantitative
      framework whereby this drive represents a multisensory self-motion estimate
      computed through an internal model that uses sensory prediction errors of
      vestibular, visual, and somatosensory cues to improve on-line motor drive. We
      show how restraint-dependent strength of recurrent connections within the
      attractor can explain differences in head direction cell firing between free
      foraging and restrained passive rotation. We also summarize recent findings on
      how gravity influences azimuth coding, indicating that the velocity drive is not
      purely egocentric. Finally, we show that the internal compass may be three
      dimensional and hypothesize that the additional vertical degrees of freedom use
      global allocentric gravity cues.

PMID- 29346753
TI  - Sonic Hedgehog Is a Remotely Produced Cue that Controls Axon Guidance Trans
      axonally at a Midline Choice Point.
AB  - At the optic chiasm choice point, ipsilateral retinal ganglion cells (RGCs) are
      repelled away from the midline by guidance cues, including Ephrin-B2 and Sonic
      Hedgehog (Shh). Although guidance cues are normally produced by cells residing at
      the choice point, the mRNA for Shh is not found at the optic chiasm. Here we show
      that Shh protein is instead produced by contralateral RGCs at the retina,
      transported anterogradely along the axon, and accumulates at the optic chiasm to
      repel ipsilateral RGCs. In vitro, contralateral RGC axons, which secrete Shh,
      repel ipsilateral RGCs in a Boc- and Smo-dependent manner. Finally, knockdown of
      Shh in the contralateral retina causes a decrease in the proportion of
      ipsilateral RGCs in a non-cell-autonomous manner. These findings reveal a role
      for axon-axon interactions in ipsilateral RGC guidance, and they establish that
      remotely produced cues can act at axon guidance midline choice points.

PMID- 29346752
TI  - Epitranscriptomic m6A Regulation of Axon Regeneration in the Adult Mammalian
      Nervous System.
AB  - N6-methyladenosine (m6A) affects multiple aspects of mRNA metabolism and
      regulates developmental transitions by promoting mRNA decay. Little is known
      about the role of m6A in the adult mammalian nervous system. Here we report that
      sciatic nerve lesion elevates levels of m6A-tagged transcripts encoding many
      regeneration-associated genes and protein translation machinery components in the
      adult mouse dorsal root ganglion (DRG). Single-base resolution m6A-CLIP mapping
      further reveals a dynamic m6A landscape in the adult DRG upon injury. Loss of
      either m6A methyltransferase complex component Mettl14 or m6A-binding protein
      Ythdf1 globally attenuates injury-induced protein translation in adult DRGs and
      reduces functional axon regeneration in the peripheral nervous system in vivo.
      Furthermore, Pten deletion-induced axon regeneration of retinal ganglion neurons
      in the adult central nervous system is attenuated upon Mettl14 knockdown. Our
      study reveals a critical epitranscriptomic mechanism in promoting injury-induced
      protein synthesis and axon regeneration in the adult mammalian nervous system.

PMID- 29346755
TI  - Connecting Neural Codes with Behavior in the Auditory System of Drosophila.

PMID- 29346754
TI  - Input-Specific NMDAR-Dependent Potentiation of Dendritic GABAergic Inhibition.
AB  - Preservation of a balance between synaptic excitation and inhibition is critical
      for normal brain function. A number of homeostatic cellular mechanisms have been
      suggested to play a role in maintaining this balance, including long-term
      plasticity of GABAergic inhibitory synapses. Many previous studies have
      demonstrated a coupling of postsynaptic spiking with modification of perisomatic
      inhibition. Here, we demonstrate that activation of NMDA-type glutamate receptors
      leads to input-specific long-term potentiation of dendritic inhibition mediated
      by somatostatin-expressing interneurons. This form of plasticity is expressed
      postsynaptically and requires both CaMKIIalpha and the beta2 subunit of the GABA
      A receptor. Importantly, this process may function to preserve dendritic
      inhibition, as genetic deletion of NMDAR signaling results in a selective
      weakening of dendritic inhibition. Overall, our results reveal a new mechanism
      for linking excitatory and inhibitory input in neuronal dendrites and provide
      novel insight into the homeostatic regulation of synaptic transmission in
      cortical circuits.

PMID- 29346756
TI  - Exploration Disrupts Choice-Predictive Signals and Alters Dynamics in Prefrontal
      Cortex.

PMID- 29346757
TI  - p53 Suppresses Metabolic Stress-Induced Ferroptosis in Cancer Cells.
AB  - How cancer cells respond to nutrient deprivation remains poorly understood. In
      certain cancer cells, deprivation of cystine induces a non-apoptotic, iron
      dependent form of cell death termed ferroptosis. Recent evidence suggests that
      ferroptosis sensitivity may be modulated by the stress-responsive transcription
      factor and canonical tumor suppressor protein p53. Using CRISPR/Cas9 genome
      editing, small-molecule probes, and high-resolution, time-lapse imaging, we find
      that stabilization of wild-type p53 delays the onset of ferroptosis in response
      to cystine deprivation. This delay requires the p53 transcriptional target CDKN1A
      (encoding p21) and is associated with both slower depletion of intracellular
      glutathione and a reduced accumulation of toxic lipid-reactive oxygen species
      (ROS). Thus, the p53-p21 axis may help cancer cells cope with metabolic stress
      induced by cystine deprivation by delaying the onset of non-apoptotic cell death.

PMID- 29346758
TI  - Size-Dependent Axonal Bouton Dynamics following Visual Deprivation In Vivo.
AB  - Persistent synapses are thought to underpin the storage of sensory experience,
      yet little is known about their structural plasticity in vivo. We investigated
      how persistent presynaptic structures respond to the loss of primary sensory
      input. Using in vivo two-photon (2P) imaging, we measured fluctuations in the
      size of excitatory axonal boutons in L2/3 of adult mouse visual cortex after
      monocular enucleation. The average size of boutons did not change after
      deprivation, but the range of bouton sizes was reduced. Large boutons decreased,
      and small boutons increased. Reduced bouton variance was accompanied by a reduced
      range of correlated calcium-mediated neural activity in L2/3 of awake animals.
      Network simulations predicted that size-dependent plasticity may promote
      conditions of greater bidirectional plasticity. These predictions were supported
      by electrophysiological measures of short- and long-term plasticity. We propose
      size-dependent dynamics facilitate cortical reorganization by maximizing the
      potential for bidirectional plasticity.

PMID- 29346760
TI  - Single-Cell Transcriptional Profiling Reveals Cellular Diversity and
      Intercommunication in the Mouse Heart.
AB  - Characterization of the cardiac cellulome, the network of cells that form the
      heart, is essential for understanding cardiac development and normal organ
      function and for formulating precise therapeutic strategies to combat heart
      disease. Recent studies have reshaped our understanding of cardiac cellular
      composition and highlighted important functional roles for non-myocyte cell
      types. In this study, we characterized single-cell transcriptional profiles of
      the murine non-myocyte cardiac cellular landscape using single-cell RNA
      sequencing (scRNA-seq). Detailed molecular analyses revealed the diversity of the
      cardiac cellulome and facilitated the development of techniques to isolate
      understudied cardiac cell populations, such as mural cells and glia. Our analyses
      also revealed extensive networks of intercellular communication and suggested
      prevalent sexual dimorphism in gene expression in the heart. This study offers
      insights into the structure and function of the mammalian cardiac cellulome and
      provides an important resource that will stimulate studies in cardiac cell
      biology.

PMID- 29346759
TI  - NF-kappaB-Chromatin Interactions Drive Diverse Phenotypes by Modulating
      Transcriptional Noise.
AB  - Noisy gene expression generates diverse phenotypes, but little is known about
      mechanisms that modulate noise. Combining experiments and modeling, we studied
      how tumor necrosis factor (TNF) initiates noisy expression of latent HIV via the
      transcription factor nuclear factor kappaB (NF-kappaB) and how the HIV genomic
      integration site modulates noise to generate divergent (low-versus-high)
      phenotypes of viral activation. We show that TNF-induced transcriptional noise
      varies more than mean transcript number and that amplification of this noise
      explains low-versus-high viral activation. For a given integration site, live
      cell imaging shows that NF-kappaB activation correlates with viral activation,
      but across integration sites, NF-kappaB activation cannot account for differences
      in transcriptional noise and phenotypes. Instead, differences in transcriptional
      noise are associated with differences in chromatin state and RNA polymerase II
      regulation. We conclude that, whereas NF-kappaB regulates transcript abundance in
      each cell, the chromatin environment modulates noise in the population to support
      diverse HIV activation in response to TNF.

PMID- 29346761
TI  - INO80 Chromatin Remodeling Coordinates Metabolic Homeostasis with Cell Division.
AB  - Adaptive survival requires the coordination of nutrient availability with
      expenditure of cellular resources. For example, in nutrient-limited environments,
      50% of all S. cerevisiae genes synchronize and exhibit periodic bursts of
      expression in coordination with respiration and cell division in the yeast
      metabolic cycle (YMC). Despite the importance of metabolic and proliferative
      synchrony, the majority of YMC regulators are currently unknown. Here, we
      demonstrate that the INO80 chromatin-remodeling complex is required to coordinate
      respiration and cell division with periodic gene expression. Specifically, INO80
      mutants have severe defects in oxygen consumption and promiscuous cell division
      that is no longer coupled with metabolic status. In mutant cells, chromatin
      accessibility of periodic genes, including TORC1-responsive genes, is relatively
      static, concomitant with severely attenuated gene expression. Collectively, these
      results reveal that the INO80 complex mediates metabolic signaling to chromatin
      to restrict proliferation to metabolically optimal states.

PMID- 29346762
TI  - Transcriptome and DNA Methylome Analysis in a Mouse Model of Diet-Induced Obesity
      Predicts Increased Risk of Colorectal Cancer.
AB  - Colorectal cancer (CRC) tends to occur at older age; however, CRC incidence rates
      have been rising sharply among young age groups. The increasing prevalence of
      obesity is recognized as a major risk, yet the mechanistic underpinnings remain
      poorly understood. Using a diet-induced obesity mouse model, we identified
      obesity-associated molecular changes in the colonic epithelium of young and aged
      mice, and we further investigated whether the changes were reversed after weight
      loss. Transcriptome analysis indicated that obesity-related colonic cellular
      metabolic switch favoring long-chain fatty acid oxidation happened in young mice,
      while obesity-associated downregulation of negative feedback regulators of pro
      proliferative signaling pathways occurred in older mice. Strikingly, colonic DNA
      methylome was pre-programmed by obesity at young age, priming for a tumor-prone
      gene signature after aging. Furthermore, obesity-related changes were
      substantially preserved after short-term weight loss, but they were largely
      reversed after long-term weight loss. We provided mechanistic insights into
      increased CRC risk in obesity.

PMID- 29346763
TI  - Derepression of the Iroquois Homeodomain Transcription Factor Gene IRX3 Confers
      Differentiation Block in Acute Leukemia.
AB  - The Iroquois homeodomain transcription factor gene IRX3 is expressed in the
      developing nervous system, limb buds, and heart, and transcript levels specify
      obesity risk in humans. We now report a functional role for IRX3 in human acute
      leukemia. Although transcript levels are very low in normal human bone marrow
      cells, high IRX3 expression is found in ~30% of patients with acute myeloid
      leukemia (AML), ~50% with T-acute lymphoblastic leukemia, and ~20% with B-acute
      lymphoblastic leukemia, frequently in association with high-level HOXA gene
      expression. Expression of IRX3 alone was sufficient to immortalize hematopoietic
      stem and progenitor cells (HSPCs) in myeloid culture and induce lymphoid
      leukemias in vivo. IRX3 knockdown induced terminal differentiation of AML cells.
      Combined IRX3 and Hoxa9 expression in murine HSPCs impeded normal T-progenitor
      differentiation in lymphoid culture and substantially enhanced the morphologic
      and phenotypic differentiation block of AML in myeloid leukemia transplantation
      experiments through suppression of a terminal myelomonocytic program. Likewise,
      in cases of primary human AML, high IRX3 expression is strongly associated with
      reduced myelomonocytic differentiation. Thus, tissue-inappropriate derepression
      of IRX3 contributes significantly to the block in differentiation, which is the
      pathognomonic feature of human acute leukemias.

PMID- 29346764
TI  - SGK1 Governs the Reciprocal Development of Th17 and Regulatory T Cells.
AB  - A balance between Th17 and regulatory T (Treg) cells is critical for immune
      homeostasis and tolerance. Our previous work has shown Serum- and glucocorticoid
      induced kinase 1 (SGK1) is critical for the development and function of Th17
      cells. Here, we show that SGK1 restrains the function of Treg cells and
      reciprocally regulates development of Th17/Treg balance. SGK1 deficiency leads to
      protection against autoimmunity and enhances self-tolerance by promoting Treg
      cell development and disarming Th17 cells. Treg cell-specific deletion of SGK1
      results in enhanced Treg cell-suppressive function through preventing Foxo1 out
      of the nucleus, thereby promoting Foxp3 expression by binding to Foxp3 CNS1
      region. Furthermore, our data suggest that SGK1 also plays a critical role in IL
      23R-mediated inhibition of Treg and development of Th17 cells. Therefore, we
      demonstrate that SGK1 functions as a pivotal node in regulating the reciprocal
      development of pro-inflammatory Th17 and Foxp3+ Treg cells during autoimmune
      tissue inflammation.

PMID- 29346765
TI  - Characterization of Endothelial Cells Associated with Hematopoietic Niche
      Formation in Humans Identifies IL-33 As an Anabolic Factor.
AB  - Bone marrow formation requires an orchestrated interplay between osteogenesis,
      angiogenesis, and hematopoiesis that is thought to be mediated by endothelial
      cells. The nature of the endothelial cells and the molecular mechanisms
      underlying these events remain unclear in humans. Here, we identify a subset of
      endoglin-expressing endothelial cells enriched in human bone marrow during fetal
      ontogeny and upon regeneration after chemotherapeutic injury. Comprehensive
      transcriptional characterization by massive parallel RNA sequencing of these
      cells reveals a phenotypic and molecular similarity to murine type H endothelium
      and activation of angiocrine factors implicated in hematopoiesis, osteogenesis,
      and angiogenesis. Interleukin-33 (IL-33) was significantly overexpressed in these
      endothelial cells and promoted the expansion of distinct subsets of hematopoietic
      precursor cells, endothelial cells, as well as osteogenic differentiation. The
      identification and molecular characterization of these human regeneration
      associated endothelial cells is thus anticipated to instruct the discovery of
      angiocrine factors driving bone marrow formation and recovery after injury.

PMID- 29346766
TI  - Cell-Type Specificity of Callosally Evoked Excitation and Feedforward Inhibition
      in the Prefrontal Cortex.
AB  - Excitation and inhibition are highly specific in the cortex, with distinct
      synaptic connections made onto subtypes of projection neurons. The functional
      consequences of this selective connectivity depend on both synaptic strength and
      the intrinsic properties of targeted neurons but remain poorly understood. Here,
      we examine responses to callosal inputs at cortico-cortical (CC) and cortico
      thalamic (CT) neurons in layer 5 of mouse prelimbic prefrontal cortex (PFC). We
      find callosally evoked excitation and feedforward inhibition are much stronger at
      CT neurons compared to neighboring CC neurons. Elevated inhibition at CT neurons
      reflects biased synaptic inputs from parvalbumin and somatostatin positive
      interneurons. The intrinsic properties of postsynaptic targets equalize
      excitatory and inhibitory response amplitudes but selectively accelerate decays
      at CT neurons. Feedforward inhibition further reduces response amplitude and
      balances action potential firing across these projection neurons. Our findings
      highlight the synaptic and cellular mechanisms regulating callosal recruitment of
      layer 5 microcircuits in PFC.

PMID- 29346767
TI  - Functional Principles of Posterior Septal Inputs to the Medial Habenula.
AB  - The medial habenula (MHb) is an epithalamic hub contributing to expression and
      extinction of aversive states by bridging forebrain areas and midbrain
      monoaminergic centers. Although contradictory information exists regarding their
      synaptic properties, the physiology of the excitatory inputs to the MHb from the
      posterior septum remains elusive. Here, combining optogenetics-based mapping with
      ex vivo and in vivo physiology, we examine the synaptic properties of posterior
      septal afferents to the MHb and how they influence behavior. We demonstrate that
      MHb cells receive sparse inputs producing purely glutamatergic responses via
      calcium-permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
      (AMPA), heterotrimeric GluN2A-GluN2B-GluN1 N-methyl-D-aspartate (NMDA) receptors,
      and inhibitory group II metabotropic glutamate receptors. We describe the complex
      integration dynamics of these components by MHb cells. Finally, we combine ex
      vivo data with realistic afferent firing patterns recorded in vivo to demonstrate
      that efficient optogenetic septal stimulation in the MHb induces anxiolysis and
      promotes locomotion, contributing long-awaited evidence in favor of the
      importance of this septo-habenular pathway.

PMID- 29346768
TI  - Activation of AMPK-Regulated CRH Neurons in the PVH is Sufficient and Necessary
      to Induce Dietary Preference for Carbohydrate over Fat.
AB  - Food selection is essential for metabolic homeostasis and is influenced by
      nutritional state, food palatability, and social factors such as stress. However,
      the mechanism responsible for selection between a high-carbohydrate diet (HCD)
      and a high-fat diet (HFD) remains unknown. Here, we show that activation of a
      subset of corticotropin-releasing hormone (CRH)-positive neurons in the rostral
      region of the paraventricular hypothalamus (PVH) induces selection of an HCD over
      an HFD in mice during refeeding after fasting, resulting in a rapid recovery from
      the change in ketone metabolism. These neurons manifest activation of AMP
      activated protein kinase (AMPK) during food deprivation, and this activation is
      necessary and sufficient for selection of an HCD over an HFD. Furthermore, this
      effect is mediated by carnitine palmitoyltransferase 1c (CPT1c). Thus, our
      results identify the specific neurons and intracellular signaling pathway
      responsible for regulation of the complex behavior of selection between an HCD
      and an HFD. VIDEO ABSTRACT.

PMID- 29346769
TI  - Switching On Depression and Potentiation in the Cerebellum.
AB  - Long-term depression (LTD) and long-term potentiation (LTP) in the cerebellum are
      important for motor learning. However, the signaling mechanisms controlling
      whether LTD or LTP is induced in response to synaptic stimulation remain obscure.
      Using a unified model of LTD and LTP at the cerebellar parallel fiber-Purkinje
      cell (PF-PC) synapse, we delineate the coordinated pre- and postsynaptic
      signaling that determines the direction of plasticity. We show that LTP is the
      default response to PF stimulation above a well-defined frequency threshold.
      However, if the calcium signal surpasses the threshold for CaMKII activation,
      then an ultrasensitive "on switch" activates an extracellular signal-regulated
      kinase (ERK)-based positive feedback loop that triggers LTD instead. This
      postsynaptic feedback loop is sustained by another, trans-synaptic, feedback loop
      that maintains nitric oxide production throughout LTD induction. When full
      depression is achieved, an automatic "off switch" inactivates the feedback loops,
      returning the network to its basal state and demarcating the end of the early
      phase of LTD.

PMID- 29346770
TI  - Integrative Analyses of De Novo Mutations Provide Deeper Biological Insights into
      Autism Spectrum Disorder.
AB  - Recent studies have established important roles of de novo mutations (DNMs) in
      autism spectrum disorders (ASDs). Here, we analyze DNMs in 262 ASD probands of
      Japanese origin and confirm the "de novo paradigm" of ASDs across ethnicities.
      Based on this consistency, we combine the lists of damaging DNMs in our and
      published ASD cohorts (total number of trios, 4,244) and perform integrative
      bioinformatics analyses. Besides replicating the findings of previous studies,
      our analyses highlight ATP-binding genes and fetal cerebellar/striatal circuits.
      Analysis of individual genes identified 61 genes enriched for damaging DNMs,
      including ten genes for which our dataset now contributes to statistical
      significance. Screening of compounds altering the expression of genes hit by
      damaging DNMs reveals a global downregulating effect of valproic acid, a known
      risk factor for ASDs, whereas cardiac glycosides upregulate these genes.
      Collectively, our integrative approach provides deeper biological and potential
      medical insights into ASDs.

PMID- 29346771
TI  - Rapid Turnover of Cortical NCAM1 Regulates Synaptic Reorganization after
      Peripheral Nerve Injury.
AB  - Peripheral nerve injury can induce pathological conditions that lead to
      persistent sensitized nociception. Although there is evidence that plastic
      changes in the cortex contribute to this process, the underlying molecular
      mechanisms are unclear. Here, we find that activation of the anterior cingulate
      cortex (ACC) induced by peripheral nerve injury increases the turnover of
      specific synaptic proteins in a persistent manner. We demonstrate that neural
      cell adhesion molecule 1 (NCAM1) is one of the molecules involved and show that
      it mediates spine reorganization and contributes to the behavioral sensitization.
      We show striking parallels in the underlying mechanism with the maintenance of
      NMDA-receptor- and protein-synthesis-dependent long-term potentiation (LTP) in
      the ACC. Our results, therefore, demonstrate a synaptic mechanism for cortical
      reorganization and suggest potential avenues for neuropathic pain treatment.

PMID- 29346772
TI  - Peroxisome Proliferator Activated Receptor Gamma Controls Mature Brown Adipocyte
      Inducibility through Glycerol Kinase.
AB  - Peroxisome proliferator-activated receptors (PPARs) have been suggested as the
      master regulators of adipose tissue formation. However, their role in regulating
      brown fat functionality has not been resolved. To address this question, we
      generated mice with inducible brown fat-specific deletions of PPARalpha,
      beta/delta, and gamma, respectively. We found that both PPARalpha and
      beta/deltadelta are dispensable for brown fat function. In contrast, we could
      show that ablation of PPARgamma in vitro and in vivo led to a reduced thermogenic
      capacity accompanied by a loss of inducibility by beta-adrenergic signaling, as
      well as a shift from oxidative fatty acid metabolism to glucose utilization. We
      identified glycerol kinase (Gyk) as a partial mediator of PPARgamma function and
      could show that Gyk expression correlates with brown fat thermogenic capacity in
      human brown fat biopsies. Thus, Gyk might constitute the link between PPARgamma
      mediated regulation of brown fat function and activation by beta-adrenergic
      signaling.

PMID- 29346773
TI  - Dual Role for DsbA in Attacking and Targeted Bacterial Cells during Type VI
      Secretion System-Mediated Competition.
AB  - Incorporation of disulfide bonds into proteins can be critical for function or
      stability. In bacterial cells, the periplasmic enzyme DsbA is responsible for
      disulfide incorporation into many extra-cytoplasmic proteins. The type VI
      secretion system (T6SS) is a widely occurring nanomachine that delivers toxic
      effector proteins directly into rival bacterial cells, playing a key role in
      inter-bacterial competition. We report that two redundant DsbA proteins are
      required for virulence and for proper deployment of the T6SS in the opportunistic
      pathogen Serratia marcescens, with several T6SS components being subject to the
      action of DsbA in secreting cells. Importantly, we demonstrate that DsbA also
      plays a critical role in recipient target cells, being required for the toxicity
      of certain incoming effector proteins. Thus we reveal that target cell functions
      can be hijacked by T6SS effectors for effector activation, adding a further level
      of complexity to the T6SS-mediated inter-bacterial interactions which define
      varied microbial communities.

PMID- 29346774
TI  - Mannose Receptor 1 Restricts HIV Particle Release from Infected Macrophages.
AB  - Human mannose receptor 1 (hMRC1) is expressed on the surface of most tissue
      macrophages, dendritic cells, and select lymphatic or liver endothelial cells.
      HMRC1 contributes to the binding of HIV-1 to monocyte-derived macrophages (MDMs)
      and is involved in the endocytic uptake of HIV-1 into these cells. Here, we
      identify hMRC1 as an antiviral factor that inhibits virus release through a bone
      marrow stromal antigen 2 (BST-2)-like mechanism. Virions produced in the presence
      of hMRC1 accumulated in clusters at the cell surface but were fully infectious.
      HIV-1 counteracted the effect by transcriptional silencing of hMRC1. The effect
      of hMRC1 was not virus isolate specific. Surprisingly, deletion of the Env
      protein, which is known to interact with hMRC1, did not relieve the hMRC1
      antiviral activity, suggesting the involvement of additional cellular factor(s)
      in the process. Our data reveal an antiviral mechanism that is active in primary
      human macrophages and is counteracted by HIV-1 through downregulation of hMRC1.

PMID- 29346775
TI  - BRD4 Promotes DNA Repair and Mediates the Formation of TMPRSS2-ERG Gene
      Rearrangements in Prostate Cancer.
AB  - BRD4 belongs to the bromodomain and extraterminal (BET) family of chromatin
      reader proteins that bind acetylated histones and regulate gene expression.
      Pharmacological inhibition of BRD4 by BET inhibitors (BETi) has indicated
      antitumor activity against multiple cancer types. We show that BRD4 is essential
      for the repair of DNA double-strand breaks (DSBs) and mediates the formation of
      oncogenic gene rearrangements by engaging the non-homologous end joining (NHEJ)
      pathway. Mechanistically, genome-wide DNA breaks are associated with enhanced
      acetylation of histone H4, leading to BRD4 recruitment, and stable establishment
      of the DNA repair complex. In support of this, we also show that, in clinical
      tumor samples, BRD4 protein levels are negatively associated with outcome after
      prostate cancer (PCa) radiation therapy. Thus, in addition to regulating gene
      expression, BRD4 is also a central player in the repair of DNA DSBs, with
      significant implications for cancer therapy.

PMID- 29346776
TI  - Loss of an Androgen-Inactivating and Isoform-Specific HSD17B4 Splice Form Enables
      Emergence of Castration-Resistant Prostate Cancer.
AB  - Castration-resistant prostate cancer (CRPC) requires tumors to engage metabolic
      mechanisms that allow sustained testosterone and/or dihydrotestosterone to
      stimulate progression. 17beta-Hydroxysteroid dehydrogenase type 4 (17betaHSD4),
      encoded by HSD17B4, is thought to inactivate testosterone and dihydrotestosterone
      by converting them to their respective inert 17-keto steroids.
      Counterintuitively, HSD17B4 expression increases in CRPC and predicts poor
      prognosis. Here, we show that, of five alternative splice forms, only isoform 2
      encodes an enzyme capable of testosterone and dihydrotestosterone inactivation.
      In contrast with other transcripts, functional expression of isoform 2 is
      specifically suppressed in development of CRPC in patients. Genetically silencing
      isoform 2 shifts the metabolic balance toward 17beta-OH androgens (testosterone
      and dihydrotestosterone), stimulating androgen receptor (AR) and CRPC
      development. Our studies specifically implicate HSD17B4 isoform 2 loss in lethal
      prostate cancer.

PMID- 29346777
TI  - PRRT2 Regulates Synaptic Fusion by Directly Modulating SNARE Complex Assembly.
AB  - Mutations in proline-rich transmembrane protein 2 (PRRT2) are associated with a
      range of paroxysmal neurological disorders. PRRT2 predominantly localizes to the
      pre-synaptic terminals and is believed to regulate neurotransmitter release.
      However, the mechanism of action is unclear. Here, we use reconstituted single
      vesicle and bulk fusion assays, combined with live cell imaging of single
      exocytotic events in PC12 cells and biophysical analysis, to delineate the
      physiological role of PRRT2. We report that PRRT2 selectively blocks the trans
      SNARE complex assembly and thus negatively regulates synaptic vesicle priming.
      This inhibition is actualized via weak interactions of the N-terminal proline
      rich domain with the synaptic SNARE proteins. Furthermore, we demonstrate that
      paroxysmal dyskinesia-associated mutations in PRRT2 disrupt this SNARE-modulatory
      function and with efficiencies corresponding to the severity of the disease
      phenotype. Our findings provide insights into the molecular mechanisms through
      which loss-of-function mutations in PRRT2 result in paroxysmal neurological
      disorders.

PMID- 29346778
TI  - Diverse Brain Myeloid Expression Profiles Reveal Distinct Microglial Activation
      States and Aspects of Alzheimer's Disease Not Evident in Mouse Models.
AB  - Microglia, the CNS-resident immune cells, play important roles in disease, but
      the spectrum of their possible activation states is not well understood. We
      derived co-regulated gene modules from transcriptional profiles of CNS myeloid
      cells of diverse mouse models, including new tauopathy model datasets. Using
      these modules to interpret single-cell data from an Alzheimer's disease (AD)
      model, we identified microglial subsets-distinct from previously reported
      "disease-associated microglia"-expressing interferon-related or proliferation
      modules. We then analyzed whole-tissue RNA profiles from human neurodegenerative
      diseases, including a new AD dataset. Correcting for altered cellular composition
      of AD tissue, we observed elevated expression of the neurodegeneration-related
      modules, but also modules not implicated using expression profiles from mouse
      models alone. We provide a searchable, interactive database for exploring gene
      expression in all these datasets (http://research
      pub.gene.com/BrainMyeloidLandscape). Understanding the dimensions of CNS myeloid
      cell activation in human disease may reveal opportunities for therapeutic
      intervention.

PMID- 29346779
TI  - Predictors of Recoverability of Renal Function after Pyeloplasty in Adults with
      Ureteropelvic Junction Obstruction.
AB  - BACKGROUND: This study aimed to identify factors predicting the recoverability of
      renal function after pyeloplasty in adult patients with ureteropelvic junction
      obstruction. METHODS: We retrospectively reviewed 138 adults with unilateral
      renal obstruction-induced hydronephrosis and who underwent Anderson-Hynes
      dismembered pyeloplasty from January 2013 to January 2016. Hydronephrosis was
      classified preoperatively according to the Society for Fetal Urology (SFU)
      grading system. All patients underwent Doppler ultrasonography, excretory
      urography, computed tomography, and technetium-99m-diethylenetriamine pentaacetic
      acid radioisotope (99mTc DTPA) renography before and after surgery. Renal
      resistive index (RRI) and 99mTc DTPA renography were repeated at 1, 3, 6, and 12
      months. RESULTS: Multivariate analysis identified age, renal pelvic type, SFU
      grade, preoperative RRI, decline of RRI, and renal parenchyma to hydronephrosis
      area ratio (PHAR) as independent predictors of renal function recoverability
      after pyeloplasty. However, preoperative RRI and RRI decline were not
      significantly associated with recoverability of renal function in patients aged
      >35 years. Lower preoperative RRI, greater decline in RRI, higher PHAR, lower SFU
      grade, and extrarenal pelvis were associated with greater improvements in
      postoperative renal function. CONCLUSIONS: Preoperative differential renal
      function cannot independently predict the recoverability of postoperative renal
      function in adult patients with unilateral renal obstruction-induced
      hydronephrosis. SFU grade, renal pelvic type, PHAR, preoperative RRI, and decline
      in RRI were significantly associated with the recoverability of renal function in
      adult patients aged <35 years, while only SFU grade, renal pelvic type, and PHAR
      were significantly associated with renal function recoverability in patients aged
      >=35 years. Renal function recovery was better in patients younger than 35 years
      when compared with older patients.

PMID- 29346780
TI  - Prevention of Aortic Dissection Suggests a Diameter Shift to a Lower Aortic Size
      Threshold for Intervention.
AB  - BACKGROUND: Multiple studies have quantified the relationship between aortic size
      and risk of dissection. However, these studies estimated the risk of dissection
      without accounting for any increase in aortic size from the dissection process
      itself. OBJECTIVES: This study aims to compare aortic size before and after
      dissection and to evaluate the change in size consequent to the dissection
      itself. METHODS: Fifty-five consecutive patients (29 type A; 26 type B) with
      aortic dissection and incidental imaging studies prior to dissection were
      identified and compared to a control group of aneurysm patients (n = 205). The
      average time between measurement at and prior to dissection was 1.7 +/- 1.9 years
      (1.9 +/- 2.0 years mean inter-image time in the control group). A multivariate
      regression model controlling for growth rate, age, and gender was created to
      estimate the effect of dissection itself on aortic size. RESULTS: The mean aortic
      sizes at and prior to dissection were 54.2 +/- 7.0 and 45.1 +/- 5.7 mm for the
      ascending aorta, and 47.1 +/- 13.8 and 39.5 +/- 13.1 mm for the descending aorta,
      respectively. The multivariable analysis revealed a significant impact of the
      dissection itself (p < 0.001) and estimated an increase in size of 7.65 mm
      (ascending aorta) and 6.38 mm (descending aorta). Thus, a proportional estimate
      of 82.8% (ascending aorta) and 80.8% (descending aorta) of dissections are made
      at a size lower than the guideline-recommended threshold (55 mm). CONCLUSIONS:
      The aortic diameter increases substantially due to aortic dissection itself and,
      thus, aortas are being dissected at clinically meaningfully smaller sizes than
      natural history analyses have previously suggested. These findings have important
      implications regarding the size at which the risk of dissection is increased.

PMID- 29346781
TI  - Laparoscopic Nephron-Sparing Calycectomy for Treating Fraley's Syndrome.
AB  - : Background/Aims/Objectives: Various nephron-sparing approaches were described
      as part of surgical management for Fraley's syndrome, a rare anatomic variant of
      the renal vascular anatomy that compresses the upper pole infundibulum resulting
      in an upper calyceal obstruction and dilatation, with symptoms of flank pain and
      hematuria. To date, descriptions of minimally invasive correction techniques are
      anecdotal. METHODS: A retroperitoneal pure laparoscopic approach using the
      nephron-sparing technique was chosen in the presented case. RESULTS: In this
      report, we demonstrated that if laparoscopic calycectomy is performed without
      clamping of renal branches, parenchymal ischemia can be completely avoided.
      Additionally, the preservation of renal tissue surrounding the calyx enables the
      preservation of the intrasinusal segmental arteries flow, thereby avoiding their
      accidental closure by hemostatic sutures. CONCLUSIONS: In conclusion,
      Laparoscopic Nephron-Sparing Calycectomy is a safe and effective surgical
      procedure for the treatment of Fraley's syndrome. Consistent laparoscopic
      experience is required before embarking on this kind of surgery.

PMID- 29346782
TI  - A Fair Chance for Everyone: Total Tumor Volume as a Selection Tool in Liver
      Transplantation for Hepatocellular Carcinoma.
AB  - : Total tumor volume (TTV) has been proposed as a more accurate means of
      selecting patients for liver transplantation (LT) due to hepatocellular carcinoma
      (HCC). We aim to analyze the role of TTV in a population with a short waiting
      time on list. METHODS: Analysis of a prospective database of patients submitted
      to LT for HCC between September 1992 and February 2014. TTV, Milan criteria (MC),
      UCSF (University of California San Francisco), and "Up to Seven" criteria were
      calculated both with preoperative imaging exams and histological data. RESULTS:
      The study population consisted of 231 out of patients. Median waiting time on
      list was 62.5 days. MC included 187 patients, while TTV <=115 cm3 included 214.
      Microvascular invasion (HR 2.601, 95% CI 1.529-4.426), MC (HR 1.666, 95% CI 0.990
      2.804), UCSF criteria (HR 2.995, 95% CI 1.875-4.875), TTV <=115 cm3 (HR 2.898,
      95% CI 1.398-6.007), and "Up to Seven" criteria (HR 2.139, 95% CI 1.353-3.383)
      proved to be independent factors for prognosis for disease-free survival.
      CONCLUSIONS: TTV <=115 cm3 may be a useful tool to properly identify the best HCC
      candidates for LT in a population with a short waiting time on list. TTV gives
      more patients the opportunity of undergoing LT while maintaining similar rates of
      tumor recurrence and patient survival.

PMID- 29346783
TI  - Does [-2]Pro-Prostate Specific Antigen Meet the Criteria to Justify Its Inclusion
      in the Clinical Decision-Making Process?
AB  - INTRODUCTION: To assess whether [-2]pro-prostate-specific antigen (p2PSA) meets
      the criteria to justify its inclusion in a predictive model of prostate cancer
      (PCa) diagnosis and in the clinical decision-making process. MATERIALS AND
      METHODS: A total 172 men with total prostate-specific antigen of 2-10 ng/mL
      underwent measurement of free PSA and p2PSA before prostate biopsy in an
      observational and prospective study. From these measurements, the Prostate Health
      Index (PHI) was calculated. Clinical and analytical predictive models were
      created incorporating PHI. RESULTS: Of 172 men, 72 (42%) were diagnosed with PCa,
      33 (46%) of whom were found to be with high-grade disease. PHI score was the most
      predictive of biopsy outcomes in terms of discriminative ability (area under the
      curve = 0.79), with an added gain in predictive accuracy of 17%. All the models
      that incorporated PHI worked better in terms of calibration close to 45 degrees 
      on the slope. In the decision curve analysis, at a threshold probability of 40%
      we could prevent 82 biopsies, missing only 16 tumors and 5 high-grade tumors.
      CONCLUSIONS: PHI score is a more discriminant biomarker, has superior calibration
      and superior net benefit, and provides a higher rate of avoided biopsies; thus,
      it can be useful for aiding in making a more informed decision for each patient.

PMID- 29346784
TI  - Surgical Treatment and Chemotherapy of Adult Primary Liver Sarcoma: Experiences
      from a Single Hospital in China.
AB  - BACKGROUND: The aim of this study is to improve the preoperative diagnostic
      accuracy and treatment results by investigating the clinical features and
      prognosis of primary liver sarcoma (PLS). METHODS: Clinical data, surgical
      treatments, adjuvant chemotherapy, and prognosis of 17 PLS patients whose
      diseases were pathologically confirmed were retrospectively analyzed. RESULTS:
      The main clinical symptoms included epigastric pain in 9 patients, epigastric
      distention in 7, and loss of appetite in 4; these symptoms were detected during
      the postoperative follow-up for gastric carcinoma in 1. The resection rate was
      64.7% (12/17), including R0 resection in 10 patients and R1 resection in 2, and
      laparotomy with biopsy in 5. Five patients accepted an adjuvant selective hepatic
      artery infusion chemotherapy (mitomycin C 16-20 mg+ 5-fluorouracil 5.0 g+
      epirubicin 40-50 mg), and 4 accepted adjuvant systemic chemotherapy (vincristin,
      cisplatin, cyclophosphamide, and adriamycin). All 5 patients with simple
      laparotomy died within 1 year, and the overall 1-, 3-, and 5-year survival rates
      for all patients were 58.8% (10/17), 29.4% (5/17) and 11.7% (2/17), respectively,
      whereas those were 100.0% (10/10), 50.0% (5/10), and 20.0% (2/10) for R0 resected
      patients respectively. CONCLUSIONS: The diagnosis of PLS is difficult before
      operation due to its nonspecific manifestations, and the high survival rate can
      be achieved by radical resection with adjuvant chemotherapy.

PMID- 29346785
TI  - Impulsivity and Saliva Cortisol in Patients with Suicide Attempt and Controls.
AB  - OBJECTIVES: The objective of this study was to prove concepts in the
      characterization of suicidal patients and the possible usefulness of those
      markers to potentially identify patients with a higher risk for suicidality.
      METHODS: Patients with a recent suicide attempt were compared with patients
      suffering from depression, adjustment disorder, anxiety, or eating disorders
      without suicidality, healthy controls and remitted patients with a history of at
      least 1 suicide attempt (>=1 year). We analyzed impulsivity (Barratt Impulsivity
      Scale, BIS) and saliva cortisol concentrations. RESULTS: Independently of
      suicidality and disease state patients display higher BIS scores than healthy
      controls. Saliva cortisol levels tend to be higher in patients in the acute
      disease state than in remitted patients and healthy controls. CONCLUSIONS: Saliva
      cortisol may be a useful marker that reveals alterations in nonsuicidal patients
      suffering from depression, adjustment disorder, anxiety, or eating disorders who
      might be at risk.

PMID- 29346786
TI  - Changing Trends in Brain Imaging Technique for Pediatric Patients with
      Ventriculoperitoneal Shunts.
AB  - BACKGROUND: Children with ventriculoperitoneal shunts (VPS) undergoing brain
      computed tomography (CT) for shunt malfunction evaluation are at risk for later
      malignancy due to radiation exposure. We aimed to determine if and how hospitals
      have adopted radiation-avoiding magnetic resonance imaging (MRI) techniques.
      METHODS: We performed a secondary analysis of the Pediatric Health Information
      System (PHIS) database. Children with VPS presenting to acute wards at 31 PHIS
      hospitals between January 1, 2007 and January 2, 2015 and receiving noncontrast
      neuroimaging on day of service 0/1 were included. Outcome measures were (1)
      incidence of MRI over time and (2) comparison of demographic characteristics
      between hospitals with MRI representing higher versus lower proportions (>15% or
      <15%) of total brain imaging. RESULTS: MRIs increased by 18.1% from 2007 to 2015.
      Hospitals were assigned to high-use (n = 12) or minimal-use (n = 19) MRI groups
      based on year 2014/2015 MRI percentages. The only identified difference was an
      older mean age in the high-use group (8.1 vs. 7.5 years; p = 0.03). CONCLUSIONS:
      MRI is increasingly used to evaluate patients with VPS. Hospitals with more MRI
      use had older patients and no increase in cost or length of stay. Initiating
      local quality improvement projects may help identify barriers to MRI uptake and
      increase use.

PMID- 29346787
TI  - Speech and Communication Changes Reported by People with Parkinson's Disease.
AB  - BACKGROUND: Changes in communicative functions are common in Parkinson's disease
      (PD), but there are only limited data provided by individuals with PD on how
      these changes are perceived, what their consequences are, and what type of
      intervention is provided. AIM: To present self-reported information about speech
      and communication, the impact on communicative participation, and the amount and
      type of speech-language pathology services received by people with PD. METHODS:
      Respondents with PD recruited via the Swedish Parkinson's Disease Society filled
      out a questionnaire accessed via a Web link or provided in a paper version.
      RESULTS: Of 188 respondents, 92.5% reported at least one symptom related to
      communication; the most common symptoms were weak voice, word-finding
      difficulties, imprecise articulation, and getting off topic in conversation. The
      speech and communication problems resulted in restricted communicative
      participation for between a quarter and a third of the respondents, and their
      speech caused embarrassment sometimes or more often to more than half. Forty-five
      percent of the respondents had received speech-language pathology services.
      CONCLUSIONS: Most respondents reported both speech and language symptoms, and
      many experienced restricted communicative participation. Access to speech
      language pathology services is still inadequate. Services should also address
      cognitive/linguistic aspects to meet the needs of people with PD.

PMID- 29346788
TI  - Vitamin D: Classic and Novel Actions.
AB  - BACKGROUND: Classically, vitamin D has been implicated in bone health by
      promoting calcium absorption in the gut and maintenance of serum calcium and
      phosphate concentrations, as well as by its action on bone growth and
      reorganization through the action of osteoblasts and osteoclasts cells. However,
      in the last 2 decades, novel actions of vitamin D have been discovered. The
      present report summarizes both classic and novel actions of vitamin D. SUMMARY:
      1,25(OH)2 vitamin D, the active metabolite of vitamin D, also known as
      calcitriol, regulates not only calcium and phosphate homeostasis but also cell
      proliferation and differentiation, and has a key a role to play in the responses
      of the immune and nervous systems. Current effects of vitamin D include
      xenobiotic detoxification, oxidative stress reduction, neuroprotective functions,
      antimicrobial defense, immunoregulation, anti-inflammatory/anticancer actions,
      and cardiovascular benefits. The mechanism of action of calcitriol is mediated by
      the vitamin D receptor, a subfamily of nuclear receptors that act as
      transcription factors into the target cells after forming a heterodimer with the
      retinoid X receptor. This kind of receptors has been found in virtually all cell
      types, which may explain its multiple actions on different tissues. Key Messages:
      In addition to classic actions related to mineral homeostasis, vitamin D has
      novel actions in cell proliferation and differentiation, regulation of the innate
      and adaptative immune systems, preventive effects on cardiovascular and
      neurodegenerative diseases, and even antiaging effects.

PMID- 29346789
TI  - Mentalization and Self-Efficacy as Mediators between Psychological Symptom
      Severity and Disabilities in Activities and Participation in Psychotherapy
      Patients.
AB  - BACKGROUND: Psychotherapy patients can be more or less disabled by their
      psychological symptoms. The present study investigated whether mentalization and
      self-efficacy contribute to the association between psychological symptom
      severity and disabilities in activities and participation. METHODS: The data of
      216 psychotherapy inpatients were examined in a cross-sectional design.
      Bootstrapping-enhanced mediation analyses were performed to investigate whether
      self-efficacy and mentalization are mediators between psychological symptom
      severity and disabilities in activities and participation. The Hamburg Modules
      for the Assessment of Psychosocial Health-49 were used to measure psychological
      symptom severity and self-efficacy, mentalization was assessed with the
      Mentalization Questionnaire, and disabilities in activities and participation
      were operationalized with the ICF-Mental-A & P questionnaire. RESULTS:
      Mentalization as well as self-efficacy functioned as mediators between
      psychological symptom severity and disabilities in activities and participation
      (p < 0.05). They were equally strong mediators, and both remained significant
      mediators when statistically controlling for the other mediator (p < 0.05).
      CONCLUSIONS: Mentalization as well as self-efficacy explain a significant
      proportion of the relationship between psychological symptom severity and
      disabilities in activities and participation. Working on mentalizing and self
      efficacy might be important mechanisms to reduce disability due to symptoms. The
      cross-sectional design is a limitation of the study.

PMID- 29346790
TI  - Multivisceral Resection for Locally Invasive Colorectal Liver Metastases:
      Outcomes of a Matched Cohort Analysis.
AB  - : Local invasion of adjacent viscera by colorectal liver metastases (CRLM) is no
      longer considered an absolute contraindication to curative hepatic resection. A
      growing number of observational analyses have illustrated the feasibility of such
      resections; however, the evidence base is at best heterogeneous with a lack of
      evidence comparing similar patient groups. We aimed to evaluate the outcomes of
      hepatectomy for CRLM when combined with other viscera and compare to a matched
      cohort of isolated hepatic resections. METHODS: From 2005 to 2015, 523 patients
      underwent hepatic resection for CRLM at our institution, 19 of whom underwent
      hepatectomy with extrahepatic resection. A 3: 1 matched cohort analysis was
      performed between those who underwent isolated hepatectomy (control group) and
      those who underwent hepatectomy with extrahepatic resection (combined group).
      Clinicopathological data were reviewed along with 30-day postoperative morbidity
      and mortality. Furthermore, overall survival for the multivisceral cohort was
      compared to all other isolated hepatectomies over the same time period. RESULTS:
      Nineteen patients underwent liver resection accompanied by either/or
      diaphragmatic resection (n = 13), major vein resection and reconstruction (n =
      5), and visceral resection (n = 3). Maximum tumor size was significantly larger
      in the combined group (60.58 vs. 15.34 mm p < 0.0001). Postoperative morbidity
      was similar in both groups (p = 0.41). Following multivisceral resection, 1-, 3-
      and 5-year survival rates were 75, 56.6, and 25.7% respectively. Overall survival
      showed no significant difference between combined and control groups (p = 0.78).
      Similarly, when compared to the total cohort of isolated liver resections (n =
      504), no significant difference in overall mortality was noted. CONCLUSION: In
      patients presenting with concomitant CRLM and extrahepatic extension where R0
      margins can be achieved, this present study supports the rationale to proceed to 
      surgery with comparable morbidity and mortality rates to -isolated hepatectomy.

PMID- 29346792
TI  - Pancreaticoduodenectomy and Outcomes for Groove Pancreatitis.
AB  - BACKGROUND/AIMS: The operative management of groove pancreatitis (GP) is still a
      matter of controversy and pancreaticoduodenectomy (PD) can be a high-risk
      procedure for patients. The aim of this study was to report our 9-year experience
      of surgical resection for GP and to review relevant literature. METHODS: A
      retrospective review of patients undergoing pancreatectomy for GP from August 1,
      2008, through May 31, 2017 was performed. Patients with clinical, radiologic, and
      final pathologic confirmation of GP were included. Literature on the current
      understanding of GP was reviewed. RESULTS: Eight patients from total 449
      pancreatectomies met inclusion criteria. Four male and 4 female patients (mean
      age, 51.9 years; mean body mass index, 25.3) underwent pylorus-preserving
      pancreatoduodenectomy (3 by laparoscopy and 5 by open approach). Mean (range)
      operative time and blood loss was 343 (167-525) min and 218 (40-500) mL
      respectively. Pancreatic fistula and delayed gastric emptying were noted in one
      patient each. No major complications occurred, but minor complications occurred
      in 5 (62%) patients. Mean hospital stay was 6.1 (range 3-14) days. At median
      follow-up of 18.15 (interquartile range 7.25-33.8) months, all patients
      experienced a resolution of pancreatitis and improvement in symptoms.
      CONCLUSIONS: PD is a safe procedure for GP. Short-term surgical outcomes are
      acceptable and long-term outcomes are associated with improved symptom control.

PMID- 29346791
TI  - Social and Behavioural Determinants of the Difference in Survival among Older
      Adults in Japan and England.
AB  - BACKGROUND: A rapidly ageing population presents major challenges to health and
      social care services. Cross-country comparative studies on survival among older
      adults are limited. In addition, Japan, the country with the longest life
      expectancy, is rarely included in these cross-country comparisons. OBJECTIVE: We
      examined the relative contributions of social and behavioural factors on the
      differences in survival among older people in Japan and England. METHODS: We used
      data from the Japan Gerontological Evaluation Study (JAGES; n = 13,176) and the
      English Longitudinal Study of Ageing (ELSA; n = 5,551) to analyse all-cause
      mortality up to 9.4 years from the baseline. Applying Laplace regression models,
      the 15th survival percentile difference was estimated. RESULTS: During the follow
      up, 31.3% of women and 38.6% of men in the ELSA died, whereas 19.3% of women and
      31.3% of men in the JAGES died. After adjusting for age and baseline health
      status, JAGES participants had longer survival than ELSA participants by 318.8
      days for women and by 131.6 days for men. Family-based social relationships
      contributed to 105.4 days longer survival in JAGES than ELSA men. Fewer
      friendship-based social relationships shortened the JAGES men's survival by 45.4
      days compared to ELSA men. Currently not being a smoker contributed to longer
      survival for JAGES women (197.7 days) and ELSA men (46.6 days), and having lower
      BMI reduced the survival of JAGES participants by 129.0 days for women and by
      212.2 days for men. CONCLUSION: Compared to participants in England, Japanese
      older people lived longer mainly because of non-smoking for women and family
      based social relationships for men. In contrast, a lower rate of underweight,
      men's better friendship-based social relationships, and a lower smoking rate
      contributed to survival among participants in England.

PMID- 29346793
TI  - Epicardial Fat Thickness in Non-Obese Neurologically Impaired Children:
      Association with Unfavorable Cardiometabolic Risk Profile.
AB  - BACKGROUND: Cardiovascular risk is reported in disabled children and epicardial
      fat (EF) is considered an independent predictor of cardiovascular disease (CVD).
      No data on the EF thickness (EFT) evaluation in disabled children have been
      published. OBJECTIVE: We investigated EFT in neurologically impaired (NI)
      children; its relationship with their metabolic profile was also considered.
      METHODS: Clinical data, body composition estimation, biochemical profile, and
      ultrasound-measured EFT were performed in 32 disabled patients (12.4 +/- 6.3
      years). Pathological parameters were defined using the following criteria: waist
      circumference >95th percentile, waist to height ratio (WHtR) >0.5, total
      cholesterol and triglycerides (TG) values >95th percentile, high density
      lipoprotein cholesterol <5th percentile, fasting blood glucose >100 mg/dL,
      homeostasis model assessment for insulin resistance (HOMA) >97.5th percentile,
      and EFT >3.6 mm. RESULTS: EFT values in NI children were higher compared with
      control group values (p = 0.02). EFT correlated with gender (p < 0.001), age (p =
      0.02), pubertal stage (p = 0.04), as well as WHtR (p = 0.03). A correlation
      between EFT and leptin was also noted (p = 0.04). EFT levels significantly
      correlated with pathological TG (p = 0.01) and HOMA-IR (p = 0.04). CONCLUSIONS:
      Higher EFT was observed in NI children compared with controls. EFT values
      correlated with clinical, metabolic, and endocrinological parameters. Ultrasound
      measured EFT could be used to promptly detect subclinical CVD and to prevent
      adverse outcomes in disabled children.

PMID- 29346795
TI  - Hello, Goodbye!

PMID- 29346794
TI  - Clinicoepidemiologic Features of Chronic Urticaria in Patients with versus
      without Subclinical Helicobacter pylori Infection: A Cross-Sectional Study of 150
      Patients.
AB  - BACKGROUND: The Helicobacter pylori infection is linked to chronic urticaria in
      nearly 60% of patients. We studied clinicoepidemiologic features in patients with
      chronic urticaria with and without H. pylori infection. METHODS: Endoscopic
      antral biopsy for the rapid urease test (RUT) and histopathology, and serum IgG
      ELISA for H. pylori infection were performed in 150 patients (male:female ratio
      1:2.4) of chronic urticaria aged 18-68 years. Clinicoepidemiologic features
      including age, gender, age of onset and duration, frequency and distribution of
      wheals, urticaria severity score, and systemic symptoms were analyzed in patients
      with and without H. pylori. The results of serum IgG ELISA for H. pylori were
      compared with 106 age- and gender-matched healthy adult controls. RESULTS: The
      RUT in 84 patients (56%), histopathology in 76 patients (50.6%), and H. pylori
      IgG ELISA in 94 patients (62.6%) were positive. H. pylori IgG ELISA was positive
      only in 35 (33%) controls, suggesting that chronic urticaria patients were more
      likely to have asymptomatic H. pylori infection than normal controls. Although
      not statistically significant, patients with H. pylori had a higher mean
      urticaria severity score, number of urticaria/angioedema episodes per year, and
      involvement of more body sites, particularly the scalp, palms, and soles. The
      constitutional or gastrointestinal symptoms were statistically higher in patients
      with H. pylori infection than those without it. CONCLUSION: A subset of chronic
      urticaria patients appears to have asymptomatic H. pylori infection. However, its
      implications in chronicity, recurrences, the severity of urticaria, other
      systemic manifestations, and management remains conjectural in view of 33% of
      controls also having positive H. pylori ELISA and the endemicity of infection in
      developing countries.

PMID- 29346796
TI  - Background Factors and Subjective Voice Symptoms in Patients with Acquired Vocal
      Fold Scarring and Sulcus Vocalis.
AB  - OBJECTIVE: Vocal fold scarring (VFS) and sulcus vocalis (SV) often result in
      severe and chronic voice disorders. This study compares subjective voice
      complaints as rated with the Voice Handicap Index and etiological factors for
      patients with VFS and SV. PATIENTS AND METHODS: Data were collected from the
      medical records at the Department of Otorhinolaryngology, Karolinska University
      Hospital, for 27 VFS patients and 27 SV patients. Descriptive background factors
      were compared between the groups and data were compared from the Swedish Voice
      Handicap Index (Sw-VHI) questionnaires. RESULTS: Previous laryngeal
      surgery/trauma was significantly more common for the patients with VFS. The SV
      group had significantly more persistent dysphonia since childhood. It was
      significantly more common to have a non-Germanic language origin among the SV
      patients. VFS and SV rated high for the total median Sw-VHI scores. The VFS
      group's total Sw-VHI and the three domain scores were significantly higher
      compared to the SV group. The physical domain showed a significantly higher score
      when compared to the functional and emotional domains in the SV cohort and when
      compared to the emotional domain in the VFS cohort. CONCLUSION: There are
      significant differences between the VFS group and SV group regarding etiological
      factors as well as the Sw-VHI. The degree and profile of VHI should be considered
      when selecting patients and evaluating the result of new treatments for this
      group of patients.

PMID- 29346797
TI  - Aortic Size and Aortic Dissection: Does One Size Fit All?

PMID- 29346798
TI  - Uric Acid in the Follow-Up Determines 30% Decline in Estimated GFR Over 2 Years:
      a Propensity Score Analysis.
AB  - BACKGROUND/AIMS: Higher level of serum uric acid (SUA) predicts early entry to
      dialysis in chronic kidney disease (CKD) patients. However, a short-term effect
      of SUA remains to be elucidated using a novel surrogate endpoint. METHODS:
      Japanese CKD stage 3 to 4 patients were retrospectively examined (n= 701). The
      follow-up level of SUA was estimated as time-averaged uric acid (TA-UA). A
      propensity score for 6.0, 6.5 or 7.0 mg/dL of TA-UA was respectively calculated
      using baseline 23 covariates. The time-to-event analysis was performed for 30%
      decline in estimated GFR over 2 years. RESULTS: Incidence rates over 2 years were
      90 of 440 in men and 36 of 261 in women (p = 0.03). Despite the negative result
      of baseline SUA, stratified Cox regression on the quintiles of the estimated
      propensity score showed that higher TA-UA of the three thresholds were all
      significant (crude HR 2.10 to 2.44) even after adjusting for the confounders.
      Kaplan-Meier analysis after propensity score matching likewise showed worse
      survival in the patients with the higher TA-UA (HR 3.11 to 4.26). CONCLUSION:
      Higher SUA increases likelihood of reaching a surrogate endpoint over 2 years.
      Early intervention for SUA less than 6.0 mg/dL is recommended for slowing CKD
      progression.

PMID- 29346799
TI  - Call for Nomination of Members of the International Standing Committee of Human
      Cytogenomic Nomenclature.

PMID- 29346800
TI  - Correction: Key differences between 13 KRAS mutation detection technologies and
      their relevance for clinical practice.
AB  - [This corrects the article DOI: 10.1136/esmoopen-2017-000235.][This corrects the
      article DOI: 10.1136/esmoopen-2017-000235.].

PMID- 29346801
TI  - Early Gene Expression Profile in Retinal Ganglion Cell Layer After Optic Nerve
      Crush in Mice.
AB  - Purpose: Optic nerve crush (ONC) induces retinal ganglion cell (RGC) death, which
      causes vision loss in glaucoma. To investigate early events leading to apoptosis
      of RGCs, we performed gene expression analysis of injured retinas in the period
      before RGC loss. Methods: The temporal changes of gene profiles at 0, 1, and 4
      days after ONC were determined by DNA microarray. To verify the gene expression
      changes in RGCs, we enriched RGCs by laser-captured microdissection and performed
      real-time RT-PCR of 14 selected genes. In situ localization study was performed
      by immunohistochemistry. Results: At 1 day and 4 days after ONC, 1423 and 2010
      retinal genes were changed compared with 0 day, respectively; these genes were
      mainly related to apoptotic process, immune process, regulation of cell cycle,
      and ion transport. RT-PCR analysis revealed that expression levels of Activating
      transcription factor 3 (Atf3), Lipocalin 2 (Lcn2), and tumor necrosis factor
      receptor superfamily member 12a (Tnfrsf12a) were remarkably changed in RGC
      enriched fraction within 4 days postcrush. Immunohistochemical analysis confirmed
      that all of these genes expressed highly in the ganglion cell layer of crushed
      retinas. Conclusions: In response to ONC, the expression of apoptotic genes was
      stimulated soon after crush. Atf3, Lcn2, and Tnfrsf12a might be key molecules
      responsible for RGC loss in glaucoma.

PMID- 29346802
TI  - Penetrance of the LHON Mutation m.11778G>A May Depend on Factors Other Than the
      Haplotype or Heteroplasmy Rate.

PMID- 29346803
TI  - Author Response: Penetrance of the LHON Mutation m.11778G>A May Depend on Factors
      Other Than Haplotype or Heteroplasmy Rate.

PMID- 29346805
TI  - Mesenteric Vessel Patency Following HIFU Therapy in Patients with Locally
      Invasive Pancreatic Cancer.
AB  - PURPOSE:  To evaluate the effects of HIFU therapy on visceral vessel patency in
      patients with inoperable locally invasive pancreatic cancer. MATERIALS AND
      METHODS:  50 pancreatic cancer patients (26 men, 24 women) aged 41 - 82 years
      (65.0 +/- 10.2) underwent ultrasonography (US) and computed tomography (CT)
      examinations before and within one day after HIFU treatment, as well as at follow
      up at six weeks, three months and six months. Evaluation and grading were
      performed by two experienced independent radiologists according to a
      classification scheme based on vessel involvement, vessel diameter, patency, and
      defects in flow. RESULTS:  Before HIFU treatment, arterial vessel involvement was
      noted in 42 patients, venous involvement in 47, and 47 patients presented with
      both. Superior mesenteric artery occlusion was found in three carcinomas while
      nearly half of the cases (n = 24) displayed signs of superior mesenteric vein,
      portal vein, or splenic vein occlusion. High-grade tumor-associated arterial
      narrowing was seen in ten patients. Despite vessel encasement and partially
      extensive propagation of collateral vessels, it was possible to safely perform
      HIFU treatment in all patients without complications. US and CT studies performed
      within one day after therapy did not show any change in vessel patency in 47
      patients (94 %). Follow-up controls at the six-week mark revealed increased
      vessel narrowing and finally occlusion after six months in 11 patients due to
      tumor progression. CONCLUSION:  This study demonstrates that HIFU treatment can
      be safely applied to pancreatic cancers enveloping large mesenteric vessels
      despite vessel narrowing or extensive collateral propagation. Most patients (94
      %) did not experience adverse effects regarding vessel patency.

PMID- 29346804
TI  - Trabodenoson, an Adenosine Mimetic With A1 Receptor Selectivity Lowers
      Intraocular Pressure by Increasing Conventional Outflow Facility in Mice.
AB  - Purpose: To evaluate the relationship between the IOP-lowering effect of
      trabodenoson and the associated structural and functional changes in the
      trabecular meshwork (TM). Methods: Six independent cohorts of young and aged mice
      were exposed to three different topical once-a-day formulations of trabodenoson
      and eyes were compared to those treated with placebo drops. IOP was measured
      daily just before drug administration using rebound tonometry. Outflow facility
      was measured in enucleated eyes. Flow patterns and morphology of conventional
      outflow tissues were monitored using tracer beads and standard histology,
      respectively. In parallel, three-dimensional human TM tissue constructs (3D-HTM)
      were grown and used in experiments to test effect of trabodenoson on the
      expression of collagen IV, fibronectin, matrix metalloproteinase (MMP)-2 and MMP
      14 plus MMP-2 activity. Results: Topical administration of trabodenoson
      significantly lowered IOP on every day tested, up to 7 days. After 2 days of
      treatment, outflow facility increased by 26% in aged mice and 30% overall (young
      and aged mice), which was significantly different from vehicle (P < 0.05).
      Outflow facility was 15% higher than controls after 7 days of treatment (P =
      0.07). While gross morphology was not affected by treatment, the intensity of
      tracer bead distribution increased by day 7 (P = 0.05). Parallel experiments in
      3D-HTM showed that trabodenoson treatment significantly increased MMP-2 activity
      and MMP-14 abundance, while decreasing fibronectin and collagen IV expression.
      Conclusions: Trabodenoson alters ECM turnover by TM cells and increases
      conventional outflow facility, which accounts for its ability to lower IOP in
      young and aged mice.

PMID- 29346806
TI  - Lithium and Renal Impairment: A Review on a Still Hot Topic.
AB  - INTRODUCTION: Lithium is established as an effective treatment of mania, of
      depression in bipolar and unipolar disorder, and in maintenance treatment of
      these disorders. However, due to the necessity of monitoring and concerns about
      irreversible adverse effects, in particular renal impairment, after long-term
      use, lithium might be underutilized. METHODS: This study reviewed 6 large
      observational studies addressing the risk of impaired renal function associated
      with lithium treatment and methodological issues impacting interpretation of
      results. RESULTS: An increased risk of renal impairment associated with lithium
      treatment is suggested. This increased risk may, at least partly, be a result of
      surveillance bias. Additionally, the earliest studies pointed toward an increased
      risk of end-stage renal disease associated with lithium treatment, whereas the
      later and methodologically most sound studies do not. DISCUSSION: The improved
      renal outcome found in the more recent lithium studies may be a result of
      improved monitoring and focus on recommended serum levels (preferentially 0.6-0.8
      mmol/L) as compared to poorer renal outcome in studies with patients treated in
      the 1960s to 1980s.

PMID- 29346807
TI  - Anti-Angiogenic Activity of Rotenoids from the Stems of Derris trifoliata.
AB  - The plants in the genus Derris have proven to be a rich source of rotenoids, of
      which cytotoxic effect against cancer cells seem to be pronounced. However, their
      effect on angiogenesis playing a crucial role in both cancer growth and
      metastasis has been seldom investigated. This study aimed at investigating the
      effect of the eight rotenoids (1: -8: ) isolated from Derris trifoliata stems on
      three cancer cells and angiogenesis. Among them, 12a-hydroxyrotenone (2: )
      exhibited potent inhibition on both cell growth and migration of HCT116 colon
      cancer cells. Further, anti-angiogenic assay in an ex vivo model was carried out
      to determine the effect of the isolated rotenoids on angiogenesis. Results
      revealed that 12a-hydroxyrotenone (2: ) displayed the most potent suppression of
      microvessel sprouting. The in vitro assay on human umbilical vein endothelial
      cells was performed to determine whether compound 2: elicits anti-angiogenic
      effect and its effect was found to occur via suppression of endothelial cells
      proliferation and tube formation, but not endothelial cells migration. This study
      provides the first evidence that compound 2: could potently inhibit HCT116 cancer
      migration and anti-angiogenic activity, demonstrating that 2: might be a
      potential agent or a lead compound for cancer therapy.

PMID- 29346808
TI  - ?

PMID- 29346809
TI  - ?

PMID- 29346810
TI  - [POEMS Syndrome].

PMID- 29346811
TI  - ?

PMID- 29346812
TI  - ?

PMID- 29346813
TI  - ?

PMID- 29346814
TI  - ?

PMID- 29346815
TI  - ?

PMID- 29346816
TI  - ?

PMID- 29346817
TI  - ?

PMID- 29346818
TI  - ?

PMID- 29346819
TI  - ?

PMID- 29346820
TI  - ?

PMID- 29346821
TI  - ?

PMID- 29346822
TI  - ?

PMID- 29346823
TI  - ?

PMID- 29346824
TI  - Antimicrobial Chemotherapy has a Linear Relationship to the Proportion of Gram
      Negative Isolates from Pediatric Burn Wounds.
AB  - : Wound infection in burns is a relevant cause of morbidity and mortality in
      children. We aimed to determine the relationship between antibacterial
      chemotherapy and Gram-negative burn wound colonization and infection. All
      children admitted to the pediatric intensive care unit for burn trauma from June
      1, 2005 to January 31, 2013 were included. We obtained 141 wound samples, of
      which 88 (65.7%) showed growth of Gram-positive bacteria. Treatment with
      antimicrobial chemotherapy was necessary in 23 (31.1%) patients. The proportion
      of Gram-negative isolates seems to increase linear from 12.5% (95% confidence
      interval (CI): 4.4%-28.7%) without antibacterial chemotherapy to 36.8% (95% CI:
      25.5%-49.6%) with one to 48.9% (95% CI: 35.3%-62.8%) with 2 antimicrobial agents.
      The Odds ratio for a Gram-negative isolate, in comparison to patients without
      antibacterial chemotherapy, increased from 4.083 (95% CI: 1.140-15.961) for one
      administered substance to 6.708 (95% CI: 1.832-26.786) if 2 or more were used.
      CONCLUSION: We found that antibacterial chemotherapy seems to facilitate burn
      wound colonization and results in an increased number of gram-negative isolates
      from children with burn wounds.

PMID- 29346825
TI  - Magnetic Resonance Imaging of Articular Cartilage within the Knee.
AB  - Magnetic resonance imaging (MRI) provides an effective and noninvasive means by
      which to evaluate articular cartilage within the knee. Existing techniques can be
      utilized to detect and monitor longitudinal changes in cartilage status due to
      injury or progression of degenerative disease. Quantitative MRI (qMRI) techniques
      can provide a metric by which to evaluate the efficacy of cartilage repair
      techniques and offer insight into the composition of cartilage and cartilage
      repair tissue. In this review, we provide background on MR signal generation and
      decay, the utility of morphologic MRI assessment, and qMRI techniques for the
      biochemical assessment of cartilage (dGEMRIC, T2, T2*, T1rho, sodium, gagCEST).
      Finally, the description and utility of these qMRI techniques for the evaluation
      of cartilage repair are discussed.

PMID- 29346826
TI  - Gastroduodenal intussusception and pylorus obstruction induced by a c-KIT
      negative gastric gastrointestinal stromal tumor: case report and review of the
      literature.
AB  - INTRODUCTION: Gastrointestinal stromal tumors (GISTs) are infrequently reported
      to cause gastroduodenal intussusception, especially in the cases with complete
      pylorus obstruction. GISTs comprise only 1 - 3 % of all gastrointestinal tract
      tumors, and most of them strongly express the c-KIT protein. Approximately 5 % of
      GISTs show negative staining of c-KIT. CASE PRESENTATION: A 69-year-old man
      complained of acute abdominal pain accompanied with nausea and vomiting for 6
      hours. Emergency endoscopic examination, upper gastroenterography, and computed
      tomography scan suggested gastroduodenal intussusception and pylorus obstruction
      induced by a gastric GIST. Laparoscopic exploration and wedge resection of the
      tumor were performed in the patient. Postoperative histological examination
      showed a gastric GIST with c-KIT-negative expression. CONCLUSION: Herein, we
      report the unique findings of a c-KIT-negative gastric GIST presenting with
      gastroduodenal intussusception and pylorus obstruction. We also reviewed the
      English language literature of gastroduodenal intussusception induced by GISTs
      and put our case in the context of the previously reported cases.

PMID- 29346827
TI  - Efficacy and complications of submucosal tunneling endoscopic resection for upper
      gastrointestinal submucosal tumors and exploration for influencing factors.
AB  - BACKGROUND: Submucosal tunneling endoscopic resection (STER) has emerged as a
      feasible technique for resecting upper gastrointestinal (GI) tract submucosal
      tumors (SMTs) through natural orifice transluminal endoscopic surgery. STER
      reduces the risk of postoperative perforation and abdominal infections and
      promotes rapid wound healing. The aim of this meta-analysis was to evaluate the
      safety and efficacy of STER for small (<= 3.5 cm) upper GI SMTs and explore the
      potential factors influencing STER's efficacy and complication rate. METHODS:
      Comprehensive literature searches were performed to find studies on STER for
      removal of SMTs. Several English-language databases were searched, including
      MEDLINE (through PubMed), EMBASE, and the Cochrane Library for the period January
      2010 to June 2016. The medical terms "submucosal tunneling endoscopic resection
      or STER", "upper gastrointestinal", and "submucosal tumors" were used in the
      search. The primary outcome measures were the pooled estimates of the complete
      resection and en bloc resection rates. The secondary outcome measure was the
      pooled estimate of complications. RESULT: Twelve studies including 397 patients
      and 430 lesions were identified. The pooled estimate of the complete resection
      rate was 98.1 % (95 % confidence interval [CI]: 95.9 - 99.2 %). The pooled
      estimate of en bloc resection was 94.9 % (95 % CI: 91.1 - 97.1 %). The pooled
      estimate of gas-related complications such as pneumoperitoneum and subcutaneous
      emphysema was 21.5 % (95 % CI: 13.2 - 33.1 %). The pooled estimate of
      inflammation-related complications including pleural and abdominal effusion was
      8.4 % (95 % CI: 5.6 - 12.3 %). Gas-related complications occurred more frequently
      in the esophagogastric junction than in the stomach. In addition, the pooled
      estimate of delayed bleeding was 2.2 % (95 % CI: 1.0 - 4.7 %). CONCLUSION: STER
      appeared to be an extremely effective technique for removing upper GI SMTs
      originating from the muscularis propria layer. In addition, the very low rate of
      complications also shows the safety of this technique. Tumor size, infiltration
      depth, and location may influence the complication rates.

PMID- 29346828
TI  - Dynamic Posterior Stabilization versus Posterior Lumbar Intervertebral Fusion: A
      Matched Cohort Study Based on the Spine Tango Registry.
AB  - PURPOSE:  The primary aim of dynamic stabilization is to stabilize the spine and
      preserve function without overstressing adjacent segments, which is a potential
      risk of fusion surgery. However, direct comparative analyses of the two
      approaches are still limited, and little is known about the association of
      patient-reported outcomes with these treatment options. OBJECTIVE:  To compare
      the clinical outcomes of dynamic posterior stabilization using the DSS
      Stabilization System (Paradigm Spine, LLC, New York, New York, United States)
      versus posterior lumbar intervertebral fusion (PLIF) based on data from a spine
      registry. We hypothesized that patient-reported outcomes of DSS are not inferior
      to those of PLIF. METHODS:  We identified 202 DSS and 269 PLIF patients with
      lumbar degenerative disease with a minimum 2-year follow-up. A 1:1 propensity
      score-based matching was applied to balance the groups for various patient
      characteristics. The primary outcome was the change in the patient-reported Core
      Outcome Measures Index (COMI; a 0-10 scale) score. RESULTS:  The matching
      resulted in 77 DSS-PLIF pairs (mean age: 67 years; average COMI follow-up: 3.3
      years) without residual significant differences in baseline characteristics. The
      groups showed no difference in improved COMI score (p = 0.69), as well as in back
      (p = 0.51) and leg pain relief (p = 0.56), blood loss (p = 0.12), and
      complications (p > 0.15). Fewer repeat surgeries occurred after DSS (p = 0.01).
      The number of repeat surgeries per 100 observed person-years was 0.8 and 2.9 in
      DSS and in PLIF patients, respectively. Furthermore, shorter surgery time (p <
      0.001) and longer hospital stays (p = 0.03) were observed for DSS cases.
      CONCLUSION:  In a midterm perspective, DSS may be a viable alternative to PLIF
      because both therapies result in similar COMI score improvement. Advantages of
      DSS may be shorter duration of surgery and fewer repeat surgeries. However, more
      than half of DSS patients did not find a match with a PLIF patient, suggesting
      that the patient profiles may be different. Further multicenter studies are
      needed to better understand the most appropriate indication for each therapy.

PMID- 29346830
TI  - Feasibility of Navigable Percutaneous Disk Decompressor (L'DISQ-C) for Cervical
      Disk Herniation.
AB  - OBJECTIVE:  To assess the procedural efficacy and safety of a Navigable
      Percutaneous Disk Decompressor (L'DISQ-C) for cervical disk herniation. METHODS: 
      We performed intradiskal decompression on cervical spine specimens from five
      human cadavers using the L'DISQ-C under C-arm fluoroscopic guidance. We evaluated
      our success for positioning the navigable wand tip into the target region and
      recorded temperature variation at various distances from the wand tip in the
      cervical nucleus pulposus. The histologic effect of plasma decompression was
      examined microscopically using harvested tissues adjacent to the procedure site.
      RESULTS:  We successfully navigated the tip of the L'DISQ-C into the target
      region of the posterior cervical disks on the first insertion attempt in all C3
      C4 to C6-C7 disks and in 50% of the C2-C3 and C7-T1 disks. The average
      temperature elevations within the nucleus pulposus ranged from 4.14 +/- 0.08
      degrees C to 12.17 +/- 0.76 degrees C at various distances from the wand tip with
      or without saline infusion. A histologic examination showed only minor
      denaturation at the marginal border of the procedure tract. CONCLUSION:  We
      effectively navigated the L'DISQ-C wand tip into the posterior target region of
      six cadaveric cervical disks and performed percutaneous resection of the target
      disk tissues without significant thermal or structural damage to adjacent
      tissues.

PMID- 29346829
TI  - Intraoperative Seizures in Awake Craniotomy for Perirolandic Glioma Resections
      That Undergo Cortical Mapping.
AB  - BACKGROUND:  Perirolandic motor area gliomas present invasive eloquent region
      tumors within the precentral gyrus that are difficult to resect without causing
      neurologic deficits. STUDY AIMS:  This study evaluates the role of awake
      craniotomy and motor mapping on neurologic outcome and extent of resection (EOR)
      of tumor in the perirolandic motor region. It also analyzes preoperative risk
      factors for intraoperative seizures. METHODS:  We evaluated 57 patients who
      underwent an awake craniotomy for a perirolandic motor area eloquent region
      glioma. Patients who had positive mapping (PM) or intraoperative identification
      of motor regions in the cortex using direct cortical stimulation were compared
      with patients with no positive motor mapping following direct cortical
      stimulation and negative mapping (NM). Preoperative risks, intraoperative
      seizures, perioperative outcomes, tumor characteristics, and EOR were also
      compared. A logistic regression model was used to evaluate the predictors for
      intraoperative seizures in this patient cohort. RESULTS:  Overall, 33 patients
      were in the PM cohort; 24 were in the NM cohort. Our study showed an 8.8%
      incidence of intraoperative seizures during cortical and subcortical mapping for
      awake craniotomies in the perirolandic motor area, none of which aborted the
      case. PM patients had significantly more intraoperative and postoperative
      seizures (15.5% and 30.3%, respectively) compared with the NM patients (0% and
      8.3%, respectively; p = 0.046 and 0.044). New transient postoperative motor
      deficits were found more often in the PM group (51.5%) versus the NM group
      (12.5%; p = 0.002). A univariate logistic regression showed that PM (odds ratio
      [OR]: 1.16; 95% confidence interval [CI], 1.01-1.34; p = 0.035) and preoperative
      tumor volume (OR: 0.998; 95% CI, 0.996-0.999; p = 0.049) were significant
      predictors for intraoperative seizures in patients with perirolandic gliomas.
      CONCLUSION:  Awake craniotomies in the perirolandic motor region can be safely
      performed with a similar incidence of intraoperative seizures as reported for the
      language cortex. PM in this region may increase the likelihood of perioperative
      seizures or motor deficits compared with NM. Craniotomies that minimize cortical
      exposure for perirolandic gliomas that may not localize motor regions can still
      allow for extensive tumor resection with a good postoperative outcome.

PMID- 29346831
TI  - Postoperative Reduction of Intraventricular Hemorrhage Volume: Single- Versus
      Dual-Catheter Drainage.
AB  - BACKGROUND/AIMS:  The use of single/dual external ventricular drains (EVD) for
      reducing intraventricular hemorrhage (IVH) is under investigation. A randomized
      controlled trial was conducted to compare postoperative reduction of IVH volume
      using single- and dual-catheter drainage in spontaneous IVH patients. We
      investigated factors that may influence an effective hematoma volume reduction by
      EVDs. MATERIALS AND METHODS:  The average cerebrospinal fluid (CSF) drainage
      volumes were analyzed. Computed tomography (CT) scans were performed on
      admission, 24 hours and 48 hours after EVD placement, and then on days 5 and 8.
      Patient group 1 was treated with a single EVD; patient group 2 was treated with
      bilateral EVDs. The IVH volume was calculated in all ventricles. A multivariate
      analysis was conducted to investigate variables that can influence the extent of
      hematoma volume reduction with a bilateral EVD. Regression followed by a Pearson
      correlation was performed to observe the strength of association of cofounders
      with the IVH volume reduction. RESULTS:  The percentage of IVH volume change was
      found to be significantly higher in the dual-catheter group compared with the
      single-catheter group (p = 0.0034) after 5 days of EVD. The mean reduction in IVH
      volume was 17.36 (mL) in patients <= 45 years of age and 20.50 (mL) in patients >
      45 years. The multivariate analysis suggested the following significant
      predictors for IVH volume reduction: age of the patient (p = 0.011) and longer
      duration (days) of EVD (p = 0.028). The age of the patient had a weak positive
      association and duration of EVD had a positive association with the IVH volume
      reduction. CONCLUSION:  Intraventricular drainage via bilateral EVDs may provide
      a better draining of blood-mixed CSF because it led to faster clot clearance. It
      is suggested that a longer duration of bilateral EVDs may lead to a greater
      reduction in IVH volume. Older patients may experience a greater IVH volume
      reduction by EVD because the volume of CSF increases with cerebral atrophy.

PMID- 29346832
TI  - Diagnosis of Lumbar Spinal Stenosis with Functional Myelography.
AB  - BACKGROUND AND STUDY AIMS:  The diagnosis of a lumbar spinal stenosis demands
      advanced diagnostic radiologic techniques. In recent decades magnetic resonance
      imaging (MRI) has replaced myelography, now considered an old-fashioned
      technique. It was our hypothesis that functional myelography still plays an
      important role in selected cases. We investigated how our surgical strategy was
      influenced by the results of MRI, functional myelography, and postmyelography
      computed tomography (CT) in patients with a lumbar spinal stenosis. METHODS:  The
      sagittal diameters of the lumbar spinal canal were measured from L1 to S1 on
      patients with lumbar spinal stenosis. MRI, functional myelography, and
      postmyelography CT were compared in each of the patients. Sensitivity and
      specificity were calculated in each method. We examined how the surgical strategy
      was influenced by the results of these different methods. RESULTS:  Fifty
      consecutive patients (21 women and 29 men; mean age: 70 years, [range: 49-86
      years]) fulfilled the inclusion criteria. Functional myelography revealed a
      sensitivity of 0.99, a specificity of 0.79, and a positive predictive value of
      0.45. The MRI exhibited a sensitivity of 0.93, a specificity of 0.74, and a
      positive predictive value of 0.39. Postmyelography CT showed a sensitivity of
      0.96, a specificity of 0.75, and a positive predictive value of 0.41. A
      functional myelography revealed more information than the MRI and resulted in a
      change in the surgical strategy in 11 of 50 patients (22%) in comparison with the
      sole results of MRI or a postmyelography CT. CONCLUSIONS:  In selected cases with
      multilevel lumbar spinal stenosis, functional myelography revealed the highest
      precision in reaching a correct diagnosis. It resulted in a change in the
      surgical approach in every fifth patient in comparison with the MRI and proved
      most helpful, especially in elderly patients.

PMID- 29346833
TI  - Phase 1b Trial of Ficlatuzumab, a Humanized Hepatocyte Growth Factor Inhibitory
      Monoclonal Antibody, in Combination With Gefitinib in Asian Patients With NSCLC.
AB  - Hepatocyte growth factor (HGF)/c-Met pathway dysregulation is a mechanism for
      epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs).
      Ficlatuzumab (AV-299; SCH 900105), a humanized IgG1 kappa HGF inhibitory
      monoclonal antibody, prevents HGF/c-Met pathway ligand-mediated activation. This
      phase 1b study assessed the safety/tolerability,
      pharmacokinetics/pharmacodynamics, and antitumor activity of ficlatuzumab plus
      gefitinib in Asian patients with previously treated advanced non-small cell lung
      cancer (NSCLC). Patients received intravenous ficlatuzumab either 10 mg/kg
      (cohort 1; n = 3) or 20 mg/kg (cohort 2; n = 12) every 2 weeks plus oral
      gefitinib 250 mg daily. Patients tolerated the drug combination well. Four
      treatment-related grade 3/4 adverse events were reported in 3 patients (cohort
      2). Pharmacokinetic profiles for ficlatuzumab and gefitinib were consistent with
      prior single-agent trials. Partial responses were achieved in 5 patients (4
      confirmed), all in cohort 2; objective response rate (ORR) was 33% (duration, 1.9
      6.4 months). Responding patients had no prior EGFR TKI treatment, 2 without an
      EGFR mutation. Four additional patients had disease stabilization (cohort 2;
      duration, 2.7-9.1 months; 42% ORR). The recommended phase 2 dose for ficlatuzumab
      plus gefitinib 250 mg/day was 20 mg/kg every 2 weeks. This drug combination has
      shown preliminary dose-related antitumor activity in advanced NSCLC.

PMID- 29346834
TI  - Twelve-week ravidasvir plus ritonavir-boosted danoprevir and ribavirin for non
      cirrhotic HCV genotype 1 patients: A phase 2 study.
AB  - BACKGROUND AND AIM: The need for all-oral hepatitis C virus (HCV) treatments with
      higher response rates, improved tolerability, and lower pill burden compared with
      interferon-inclusive regimen has led to the development of new direct-acting
      antiviral agents. Ravidasvir (RDV) is a second-generation, pan-genotypic NS5A
      inhibitor with high barrier to resistance. The aim of this phase 2 study (EVEREST
      study) was to assess the efficacy and safety of interferon-free, 12-week RDV plus
      ritonavir-boosted danoprevir (DNVr) and ribavirin (RBV) regimen for treatment
      naive Asian HCV genotype 1 (GT1) patients without cirrhosis. METHODS: A total of
      38 treatment-naive, non-cirrhotic adult HCV GT1 patients were enrolled in this
      multicenter, open-label, single-arm phase 2 study (NCT03020095). All patients
      received a combination of RDV 200 mg once daily (q.d.) plus DNVr 100 mg/100 mg
      twice daily (b.i.d.) and oral RBV 1000/1200 mg/day (body weight < 75/>= 75 kg)
      for 12 weeks. The primary endpoint was the rate of sustained virologic response
      12 weeks after the end of treatment (SVR12). RESULTS: Of 38 patients, all (100%)
      achieved SVR12. During the study, no treatment-related serious adverse events, no
      patients discontinued treatment due to adverse events, and no deaths were
      reported. Six of 37 (16%) patients with available sequences had HCV NS5A
      resistance-associated variants at baseline. All patients (6/6) with baseline NS5A
      resistance-associated variants achieved SVR12. CONCLUSIONS: Twelve-week RDV and
      DNVr in combination with RBV for 12 weeks achieves the SVR12 rate of 100% in
      treatment-naive non-cirrhotic Asian patients with HCV GT1 infection. This
      interferon-free regimen is also safe and well tolerated.

PMID- 29346835
TI  - Two citrate transporters coordinately regulate citrate secretion from rice bean
      root tip under aluminum stress.
AB  - Aluminum (Al)-induced organic acid secretion from the root apex is an important
      Al resistance mechanism. However, it remains unclear how plants fine-tune root
      organic acid secretion which can contribute significantly to the loss of fixed
      carbon from the plant. Here, we demonstrate that Al-induced citrate secretion
      from the rice bean root apex is biphasic, consisting of an early phase with low
      secretion and a later phase of large citrate secretion. We isolated and
      characterized VuMATE2 as a possible second citrate transporter in rice bean
      functioning in tandem with VuMATE1, which we previously identified. The time
      dependent kinetics of VuMATE2 expression correlates well with the kinetics of
      early phase root citrate secretion. Ectopic expression of VuMATE2 in Arabidopsis
      resulted in increased root citrate secretion and Al resistance.
      Electrophysiological analysis of Xenopus oocytes expressing VuMATE2 indicated
      VuMATE2 mediates anion efflux. However, the expression regulation of VuMATE2
      differs from VuMATE1. While a protein translation inhibitor suppressed Al-induced
      VuMATE1 expression, it releases VuMATE2 expression. Yeast one-hybrid assays
      demonstrated that a previously identified transcription factor, VuSTOP1,
      interacts with the VuMATE2 promoter at a GGGAGG cis-acting motif. Thus, we
      demonstrate that plants adapt to Al toxicity by fine-tuning root citrate
      secretion with two separate root citrate transport systems.

PMID- 29346836
TI  - Emergency demand, repeat and frequent presentations by older patients in
      metropolitan Melbourne: A retrospective cohort study using routinely collected
      hospital data.
AB  - OBJECTIVE: To describe patterns for potentially avoidable general practice (PAGP)
      type and non-PAGP-type ED presentations by older patients during 2008 and 2012.
      METHODS: Retrospective analysis of ED presentations by patients >=70 years for
      2008 and 2012. Metropolitan Melbourne public hospital data were obtained from the
      Victorian Emergency Minimum Dataset. Outcomes were characteristics of PAGP-type
      and non-PAGP-type presentations as defined by the Australian Institute of Health
      and Welfare; numbers and rates per 1000 population >=70 years of repeat (*2
      3/year) and frequent (>= *4/year) PAGP-type and non-PAGP-type presentations.
      RESULTS: The older metropolitan Melbourne population increased by 10.3% between
      2008 and 2012, whereas the number of ED presentations increased by 12.7%. The
      volume of PAGP-type presentations decreased by 2.6%, with declining rates per
      1000 population >=70 years of repeat (7.2-6.2) and frequent (0.7-0.4)
      presentation. In contrast, the volume of non-PAGP-type presentations grew by
      15.4%, with increasing repeat (57.6-60.7) and frequent (13.1-14.2) presentation
      rates per 1000 population >=70 years. The majority (39%) of non-PAGP-type
      presentations by frequent ED attenders were due to cardiovascular or respiratory
      problems. CONCLUSION: The rate of repeat and frequent PAGP-type presentations by
      older people decreased in 2012 compared with 2008, suggesting that initiatives
      implemented to reduce avoidable presentations may have had an effect. However, an
      increase in the rate of frequent non-PAGP-type presentations, predominately for
      acute exacerbation of cardiovascular and respiratory conditions, has important
      implications for planning future healthcare delivery; hence, the importance of
      initiatives such as the Health Care Home.

PMID- 29346837
TI  - A Phase 1, Randomized, Placebo- and Active-Controlled Crossover Study to
      Determine the Effect of Single-Dose Ertugliflozin on QTc Interval in Healthy
      Volunteers.
AB  - Ertugliflozin, a selective sodium-glucose cotransporter-2 inhibitor, is being
      developed for the treatment of type 2 diabetes mellitus. This randomized, 6
      sequence, 3-period crossover study assessed the effect of ertugliflozin (100 mg;
      supratherapeutic dose) vs placebo and moxifloxacin (400 mg; positive control) on
      the QT interval corrected for heart rate (QTc) in 42 male or female healthy
      subjects. Triplicate electrocardiograms were performed predose and serially over
      48 hours postdose in each treatment period. The maximum observed least-squares
      mean (90% CI) difference in QTc using the Fridericia correction (QTcF) between
      ertugliflozin and placebo was 2.99 (1.68, 4.30) milliseconds, 24 hours postdose,
      below the 5-millisecond threshold of potential clinical concern. The upper limits
      of the 2-sided 90% CI were less than 10 milliseconds at all postdose time points.
      The lower 90% CIs for the least-squares mean QTcF difference between moxifloxacin
      and placebo were greater than 5 milliseconds at the preselected time points of 2,
      3, and 4 hours postdose, establishing study sensitivity. The majority of adverse
      events were mild in severity. In healthy volunteers, at a supratherapeutic dose
      of 100 mg, ertugliflozin was not associated with QTc interval prolongation.

PMID- 29346839
TI  - Prepared for the future.

PMID- 29346840
TI  - Into the future.

PMID- 29346838
TI  - First-in-human study to assess the safety, pharmacokinetics and pharmacodynamics
      of BMS-962212, a direct, reversible, small molecule factor XIa inhibitor in non
      Japanese and Japanese healthy subjects.
AB  - AIMS: The aims of the present study were to assess the safety, pharmacokinetics
      (PK) and pharmacodynamics (PD) of BMS-962212, a first-in-class factor XIa
      inhibitor, in Japanese and non-Japanese healthy subjects. METHODS: This was a
      randomized, placebo-controlled, double-blind, sequential, ascending-dose study of
      2-h (part A) and 5-day (part B) intravenous (IV) infusions of BMS-962212. Part A
      used four doses (1.5, 4, 10 and 25 mg h-1 ) of BMS-962212 or placebo in a 6:2
      ratio per dose. Part B used four doses (1, 3, 9 and 20 mg h-1 ) enrolling
      Japanese (n = 4 active, n = 1 placebo) and non-Japanese (n = 4 active, n = 1
      placebo) subjects per dose. The PK, PD, safety and tolerability were assessed
      throughout the study. RESULTS: BMS-962212 was well tolerated; there were no signs
      of bleeding, and adverse events were mild. In parts A and B, BMS-962212
      demonstrated dose proportionality. The mean half-life in parts A and B ranged
      from 2.04 to 4.94 h and 6.22 to 8.65 h, respectively. Exposure-dependent changes
      were observed in the PD parameters, activated partial thromboplastin time (aPTT)
      and factor XI clotting activity (FXI:C). The maximum mean aPTT and FXI:C change
      from baseline at 20 mg h-1 in part B was 92% and 90%, respectively. No difference
      was observed in weight-corrected steady-state concentrations, aPTT or FXI:C
      between Japanese and non-Japanese subjects (P > 0.05). CONCLUSION: BMS-962212 has
      tolerability, PK and PD properties suitable for investigational use as an acute
      antithrombotic agent in Japanese or non-Japanese subjects.

PMID- 29346841
TI  - Granulomatous interstitial nephritis associated with silica.

PMID- 29346842
TI  - Dapagliflozin associated ketoacidosis: A must know fact for nephrologists.

PMID- 29346843
TI  - Misdiagnosed as osteosarcoma: Brown tumour in a haemodialysis patient.

PMID- 29346844
TI  - Conversion of renal abstracts to papers: Published or perished?

PMID- 29346845
TI  - A New Approach to the Evaluation of Local Muscular Load while Typing on a
      Keyboard.
AB  - OBJECTIVE: The aim of this study was to assess the contribution of using
      keystroke dynamics (KD) in combination with integrated electromyography (iEMG)
      for the objective evaluation of local muscular load of hands and forearms while
      typing on a computer keyboard and to compare it with results of the commonly used
      method. METHOD: Study was performed on 12 subjects. Data were collected using our
      own application for capturing KD data and using EMG Holter for detecting
      electromyographic potentials to determine local muscular load. RESULTS: The
      results of our study revealed that currently used methods for assessment of the
      workload while typing on a computer keyboard are not entirely accurate. In
      particular, the real total number of keystrokes performed during processing of a
      text is significantly higher than the count of characters the text is consisting
      of. In addition to this count, also the so-called invisible keys, keyboard
      shortcuts, and especially corrections in the typed text must be taken into
      consideration. CONCLUSIONS: The results indicated that all probands in our study
      exceeded the valid hygienic limits for the total amount of the small repetitive
      movements of the hands and forearms and the total amount of the keyboard typing
      movements. Most of the probands in our study also exceeded the valid hygienic
      limit for the highest average time-weighted value of the percent maximum
      voluntary contraction (%MVC). This implies that the keystroke dynamics method has
      a great potential to increase the accuracy of evaluation of local muscular load
      when using the keyboard and thus to improve the existing methodology for
      investigation of occupational diseases resulting from overload while working on
      the computer.

PMID- 29346846
TI  - Legislative Norms to Control Cannabis Use in the Light of Its Prevalence in Czech
      Republic, Poland, Slovakia, and Hungary.
AB  - OBJECTIVES: Cannabis control legislation ranks among key measures to prevent
      social-health impacts of its use. The article qualitatively analyses respective
      legislation in the Czech Republic, Poland, Slovakia, and Hungary (Visegrad Four,
      V4) considering level of decriminalisation of cannabis use in relation to current
      epidemiological situation. METHODS: Qualitative analysis of the cannabis control
      legislation in V4 countries from 1995 to 2016 focusing on criminal liability,
      differentiation of cannabis from other illicit substances, definition of a small
      amount intended for personal use, sentences for possessing and dealership of the
      drug. Results: Slovakia, Hungary and Poland share similar restrictive legislative
      approach throughout the studied period. In the Czech Republic, the situation has
      been different and since 2010 cannabis has been further decriminalised:
      possession of defined small amount of drug not being under prosecution and milder
      sentences for cannabis than for other illicit psychoactive substances. RESULTS:
      Slovakia, Hungary and Poland share similar restrictive legislative approach
      throughout the studied period. In the Czech Republic, the situation has been
      different and since 2010 cannabis has been further decriminalised: possession of
      defined small amount of drug not being under prosecution and milder sentences for
      cannabis than for other illicit psychoactive substances. CONCLUSION: Although the
      prevalence of cannabis use among adolescents is the highest in the Czech
      Republic, partial decriminalisation did not show further increase. Slovakia,
      Hungary and Poland show different trends in epidemiological situation despite of
      similar legislative approach. Results indicate that beside legislation other
      social factors play a role and measures to change attitudes and decrease social
      tolerance are important.

PMID- 29346847
TI  - Manner of Death of Older People with Regard to Blood Alcohol Concentration.
AB  - OBJECTIVE: Alcohol abuse is related to a wide variety of negative health outcomes
      including mortality in older people. Alcohol abuse in older people is
      characterised by certain specific features uncommon in general adult population.
      The main objective of this study was to analyse the autopsy protocols of deceased
      older people in relation to blood alcohol concentration (BAC), sex, age, and
      manner of death. As a positive BAC, >0.20 g/kg was accepted. METHODS: The sample
      consists of 1,012 deceased older people (i.e. aged 65 years and over) selected
      out of 2,377 autopsied subjects in the period from 2003-2013. Subjects included
      into the sample were chosen via the proportional sampling method. Data (BAC, sex,
      age, and manner of death) was recorded in a single structured protocol. Data was
      evaluated statistically (Kolmogorov-Smirnov two-sample test, Wilcoxon two-sample
      test, risk ratio). RESULTS: Among older people, there has been a statistically
      significant correlation of natural death with sex (men died earlier) and with
      increased BAC (people with positive BAC died earlier). In case of violent death
      there is a difference in the types of accidents in older people with positive BAC
      (>0.2 g/kg) and with negative BAC (<=0.2 g/kg). Drowning is more common in older
      people with positive BAC. CONCLUSIONS: Health campaigns in Europe and the Czech
      Republic aimed at reducing alcohol consumption mainly deal with young people.
      Alcohol abuse has an impact on premature mortality even in older people. As shown
      by this study, older people with positive BAC die significantly earlier.

PMID- 29346848
TI  - Factors Influencing Suicidal Tendencies of Patients with Diagnosis of Attempted
      Suicide in Medical History and Potential Prevention of Relapse Prevention.
AB  - OBJECTIVE: The authors researched the incidence of suicidal thoughts and related
      factors in 123 patients of the psychiatric ward of the Hospital of Ceske
      Budejovice with diagnosed attempted suicide in their medical history for the
      period from January 2013 - June 2015. METHODS: The research was carried out in
      two stages. At the beginning of the hospitalization, quantitative data collection
      was implemented using a semi-structured questionnaire, followed by qualitative
      research conducted with semi-structured phone conversation, based on previous
      patient's written consent. The research data were statistically processed to
      obtain information about the character of relations among individual
      characteristics. To quantify them, the Bayesian Network (BN) was constructed, and
      to identify relations among individual characteristics, the Hill-Climbing
      algorithm was used. Before deriving the network, variables were discretized. The
      network parameters were set based on a data matrix using the maximal plausibility
      method. RESULTS: The results of analysed set show that the probability of
      suicidal thoughts is high, achieving a value of 0.750 (0.781 for women and 0.724
      for men). If the patient visits a contact centre for drug-addicted persons, the
      probability of suicidal thoughts decreases to 0.683. If the patient visits a
      psychotherapist, the values of 0.736 are achieved. If a daily care centre is
      visited, the estimated risk rises to 0.832 and the probability of the patient
      repetitively attempting suicide is 0.606. If the interviewed person regularly
      consumes alcohol, the probable relapse amounts to 0.616. But if the person
      consumes alcohol from time to time, the probability rises to 0.701. In case of
      abstinence, the probable relapse decreases to 0.565. CONCLUSIONS: The incidence
      of suicidal thoughts in observed patients was high, and the amount of risk was
      influenced by gender, by visiting follow-up care facilities, psychotherapy, and
      particularly by the frequency of alcohol consumption. Intermittent alcohol
      consumption is the highest-risk factor in connection with relapsing suicide. In
      case of psychiatric patients with attempted suicide in their medical history, all
      verified preventive and therapeutic procedures that can contribute to prevention
      of relapses should be used within follow-up professional care. Specific approach
      of the closest social environment, medical literacy of the population and state
      safety measures are important.

PMID- 29346849
TI  - Syphilis Resurgence in Belgrade, Serbia, in the New Millennium: An Outbreak in
      2014.
AB  - OBJECTIVE: A worldwide syphilis incidence increase was recorded at the beginning
      of the new millennium, occurring primarily among men who have sex with men (MSM).
      The aim of this study was to analyse the epidemiological situation of syphilis in
      the Belgrade population between 2005 and 2014 and to examine the characteristics
      of an early syphilis outbreak among MSM in Belgrade in 2014. METHOD: Reporting of
      syphilis is compulsory in Serbia. Routinely reported data were analysed along
      with data collected from patients' charts. RESULTS: During the period observed,
      syphilis incidence increased from 1.07 per 100,000 in 2005 to 4.1 per 100,000 in
      2014 (383.2%). From 2005 to 2009, syphilis rates in Belgrade were low, around 1
      case per 100,000 people. The first outbreak was registered in 2010. The new
      incidence increase happened in 2012, and again in 2014 when it was the highest.
      These incidence changes were registered mainly in men, where the frequency of
      syphilis was much higher than in women. In 2014, primary syphilis was diagnosed
      in 20 cases, secondary syphilis in 42, and early latent syphilis in 9 patients.
      Fifty-seven were MSM, 10 were heterosexual men and 4 were women. Twenty-four
      cases, all MSM were co-infected with HIV. Majority of patients acquired infection
      in Belgrade, while in 42/71 cases oral sex was the only risk factor. In
      comparison with HIV negative, HIV positive syphilis patients were older, more
      frequently unemployed and MSM. They also more frequently had sex with unknown
      partners and were diagnosed in the secondary stage of infection. CONCLUSIONS:
      Study results underline the need for coordinated and expeditious surveillance,
      partner services, enhanced screening of population at risk, health education, as
      well as early diagnosis and treatment.

PMID- 29346850
TI  - Trends in the Minimum Inhibitory Concentrations of Erythromycin, Clarithromycin,
      Azithromycin, Ciprofloxacin, and Trimethoprim/Sulfamethoxazole for Strains of
      Bordetella pertussis isolated in the Czech Republic in 1967-2015.
AB  - OBJECTIVE: The aim of the study was to determine trends in the minimum inhibitory
      concentrations (MICs) of erythromycin used as first-line therapy and alternative
      antibiotics against Bordetella pertussis (B. pertussis) strains isolated from
      patients with whooping cough in the Czech Republic (CR) in three periods from
      1967 to 2015. METHODS: In total, 135 isolates from the years 1967-2015 were
      analysed. The strains were divided into three groups by the year of isolation:
      1967-1999 (42 strains), 2004-2010 (43 strains), and 2011-2015 (50 strains). MIC
      of selected antibiotics (erythromycin, clarithromycin, azithromycin,
      ciprofloxacin, and trimethoprim/sulfamethoxazole) were obtained by the reference
      agar dilution method on Bordet Gengou Agar with 15% defibrinated sheep blood.
      RESULTS: The study set included 70 strains previously tested for MICs of
      erythromycin and four other antibiotics. In the three study periods, the MICs of
      the tested antibiotics for B. pertussis were nearly identical. All but a single
      strain, inhibited by erythromycin at a concentration of 0.03 mg/l, were inhibited
      by two concentrations of erythromycin and azithromycin (0.06 and 0.125 mg/l).
      Clarithromycin inhibited the strains from all three study periods at the
      following concentrations: 0.03, 0.06, and 0.125 mg/l. Any of the 135 strains was
      inhibited by ciprofloxacin at a single concentration of 0.06 mg/l and by
      trimethoprim/sulfamethoxazole at three concentrations (0.125, 0.25, and 0.5
      mg/l). CONCLUSION: The study set of 135 Czech strains of B. pertussis isolated in
      1967-2015 appears to be homogeneous in terms of the MICs for five antimicrobials.
      The MICs remained in a narrow range of two to three low concentrations; the
      unimodal distribution of the MICs suggests the absence of resistance mechanisms.
      The highest MICs of erythromycin, clarithromycin, and azithromycin were equally
      0.125 mg/l, that of ciprofloxacin was 0.06 mg/l, and that of
      trimethoprim/sulfamethoxazole was 0.5 mg/l. Over the study period of 55 years,
      the MICs of the study antibiotics remained in the same ranges.

PMID- 29346851
TI  - A Nurse-Led School-Based Sun Protection Programme in Turkey.
AB  - OBJECTIVE: The aim of this study was to determine the effects of a nurse-led
      school-based sun protection programme in Turkey. METHODS: A randomized controlled
      trial was performed at two public schools between February and October 2014.
      Children with written consent from their parents were screened by nurses for skin
      type, and 80 children at moderate to high risk for skin cancer were included in
      the study. The sample was randomized by age, gender and skin type. Stratified and
      block randomizations were used. The participants were separated into an
      intervention group (n=40) and control group (n=40). Data were collected using a
      personal information form and two scales for sun protection behaviour and self
      efficacy. RESULTS: In the intervention group, the pretest mean score for sun
      protection behaviour was 19.25+/-5.44 and increased significantly in the posttest
      assessment (33.05+/-4.23, p<0.001). Self-efficacy scores also increased
      significantly after the intervention (pretest 20.50+/-6.68, post-test 35.85+/
      4.70, p<0.001). However, there were no significant increases in mean sun
      protection behaviour or self-efficacy scores in the control group (p>0.05).
      CONCLUSION: A nurse-led school-based sun protection programme effectively
      promoted children's self-efficacy and sun protection behaviour.

PMID- 29346852
TI  - Symptomatic Response of the Elderly with Cardiovascular Disease during a Heat
      Wave in Slovenia.
AB  - OBJECTIVE: The aim of this study is to analyse the symptomatic response of
      elderly people to heat burden and indoor air quality exposure, and to create an
      index, the basis on which healthcare workers could react and prevent heat-related
      illnesses when the first symptoms appear. METHODS: The impact of the indoor
      thermal environment was studied with regards to Humidex and indoor air quality by
      CO2 concentrations on elderly people's symptomatic response. It was a natural
      experiment in which two different groups of elderly people (>65 years) were
      observed: the first group had a diagnosed cardiovascular disease, and the second
      group did not have the disease. RESULTS: The results show that the expression and
      aggravation of symptoms are related to an increase of heat burden and low indoor
      air quality. The symptoms under analysis do not have the same frequency
      distribution of intensity and, therefore, cannot be interpreted as a single
      universal symptom index. Instead, two indices must be created separately for both
      general and specific symptoms. CONCLUSIONS: Healthcare workers should be educated
      about the interactive influences of the thermal environment and the air quality
      on health. Unsuitable conditions could be ascertained by the nursing home
      occupants' symptomatic response.

PMID- 29346853
TI  - Selected Cardiovascular Risk Markers in Vegetarians and Subjects of General
      Population.
AB  - OBJECTIVE: Besides genetic factors there are environmental effects including
      nutritional habits which can influence the risk of age-related diseases. The aim
      of the study was to assess the age dependence of selected cardiovascular risk
      markers in two groups of subjects with different nutritional pattern. METHODS: In
      470 long-term vegetarians and 478 subjects of general population the following
      indicators were measured: total cholesterol, HDL-cholesterol, triacylglycerol,
      glucose, insulin concentrations, LDL-cholesterol, atherogenic index and insulin
      resistance IR(HOMA) were also calculated in studied subjects. Obtained data were
      evaluated according to age decades. RESULTS: Vegetarian vs. non-vegetarian
      concentrations of total cholesterol, LDL-cholesterol, insulin, and values of
      atherogenic index and IR(HOMA) were significantly reduced in all age decades.
      Vegetarian vs. non-vegetarian triacalglycerol concentrations were significantly
      reduced from 4th-7th decade. Vegetarian average decade values of all lipid
      parameters were in reference range. In non-vegetarian group, the risk average
      values of total cholesterol (>5.2 mmol/l) were found from 5th-7th decade, LDL
      cholesterol (>3.3 mmol/l) in 7th decade and atherogenic index (>4) in 6th-7th
      decade. In vegetarians vs. non-vegetarians were noted the average decade values
      for total cholesterol ranging from 4.01-4.59 vs. 4.48-5.67 mmol/l, for
      triacylglycerols 1.00-1.33 vs. 1.13-1.74 mmol/l, for LDL-cholesterol 2.03-2.58
      vs. 2.43-3.49 mmol/l, for atherogenic index 2.72-3.31 vs. 3.05-4.21 and for
      IR(HOMA) 0.99-1.15 vs. 1.15-1.84. CONCLUSION: Our data show significantly reduced
      mean age decade values of lipid and non-lipid cardiovascular risk markers in all
      adult vegetarians. Smaller changes of markers between decades compared to non
      vegetarians document a protective effect of vegetarian nutrition in prevention of
      cardiovascular disease.

PMID- 29346854
TI  - High Participation Rate in Mammography Screening: Experience from Croatia.
AB  - OBJECTIVE: The aim of the study was to analyse the results of three cycles of
      mammography screening (MS) in the Croatian National Programme (CNP) for Early
      Breast Cancer Detection for women aged 50-69 years in the Bjelovar-Bilogora
      County (BBC) from 2006-2014. METHODS: Data on women aged 50-69 screened during a
      9-year period were obtained from the Croatian Cancer Registry and Institute of
      Public Health reports. Participation rate and performance indicators were
      examined. RESULTS: The total of 57,428 women were invited to mammography
      screening in BBC during a 9-year period and 31,402 mammograms in total were
      performed. The response rate of 84% in BBC was consistently higher than the
      national average of about 60% reported in 2007, 2013 and 2014. CONCLUSION: The
      National Programme in BBC has been carried out continuously for nine years with a
      higher response rate compared with the national average, as a result of
      additional efforts of the Croatian Institute of Public Health team, as well as
      good cooperation among all programme stakeholders. It was concluded that to
      achieve better results in the response of women to screening and consequently
      reduced mortality from breast cancer is possible through tailored health
      promotion activities.

PMID- 29346855
TI  - Do Adolescents with T1DM Differ from Their Peers in Health, Eating Habits and
      Social Support?
AB  - OBJECTIVE: The aim of this study was to analyse differences in health, eating
      habits and social support in adolescents with type 1 diabetes mellitus (T1DM) in
      comparison to peers with another long-term illness or without any medical
      condition. METHODS: We used self-reported data from the cross-sectional Health
      Behaviour in School-aged Children study collected in 2014 among Slovak
      adolescents as well as data from adolescents with T1DM collected in outpatient
      settings (11 to 15 years old, N=8,910, 50.3% of boys). Logistic regression models
      and general linear models were used to analyse differences between adolescents
      with T1DM and their peers with and without long-term illness in self-rated
      health, life satisfaction, health complaints, regular breakfast, sweets and soft
      drink consumption, and perceived support from family, teachers and classmates.
      RESULTS: Adolescents with T1DM reported worse self-rated health and suffer from
      more health complaints, but they have lower chance of having breakfast
      irregularly in comparison to their peers with another long-term illness or
      without any medical condition. Moreover, compared with their peers, adolescents
      with T1DM perceived stronger support from teachers and classmates, but weaker
      support from their family. We did not confirm any differences in life
      satisfaction, sweets and soft drink consumption between adolescents with T1DM and
      their peers. CONCLUSIONS: Adolescents with T1DM reported more regular eating
      habits, no difference in life satisfaction and more social support outside the
      family in comparison to their peers. However, their worse self-rated health, more
      health complaints and weaker support from family should be considered in
      interventions targeting psychosocial adjustment of adolescents with T1DM.

PMID- 29346856
TI  - Prevalence and Trends of Metabolic Syndrome in Slovakia during the Period of 2003
      2012.
AB  - OBJECTIVE: Metabolic syndrome is a combination of clinical risk factors for
      cardiovascular disease as well as for diabetes. Metabolic syndrome arises from
      insulin resistance accompanied with abnormal adipose deposition. The aim of our
      cross-sectional time trends study was to characterize the prevalence of metabolic
      syndrome and its five risk determinants among the clients of Health Advice
      Centres of Regional Public Health Authorities in Slovakia. The study was
      stratified by gender and age groups during the 10 year period from 2003-2012.
      METHODS: Prevalence data were estimated in adults and children (>=10 years,
      N=79,904) from the nationwide electronic database of Health Advice Centres of
      Regional Public Health Authorities in Slovak Republic "Test of healthy heart"
      from 2003 to 2012. RESULTS: The overall prevalence of metabolic syndrome was
      30.2% in males and 26.6% in females, abdominal obesity was confirmed in 48.3% of
      males and 53.9% of females. Increased triglyceride level has higher prevalence
      among males (33.3%) compared to females (24.2%). Blood pressure (BP) values and
      fasting glucose values were significantly higher in males (58.2%) than females
      (41.9%). During the 10 year period from 2003 to 2012, we confirmed an increased
      trend in the age-adjusted prevalence of metabolic syndrome. Abdominal obesity and
      elevated triglycerides had also increased time trends prevalence in both sexes.
      The prevalence of people without risk determinants of metabolic syndrome had a
      time decreasing trend. A surprising finding is a decrease in the proportion of
      persons with suboptimal HDL-cholesterol. The proportion of people with elevated
      BP and glucose showed little change during the reporting period. CONCLUSION: The
      increasing prevalence of metabolic syndrome, abdominal obesity, and elevated
      triglycerides highlights the urgency of addressing these health problems as a
      healthcare priority to reduce cardiovascular mortality in the Slovak Republic.

PMID- 29346857
TI  - Higher Energy Intake Variability as Predisposition to Obesity: Novel Approach
      Using Interquartile Range.
AB  - OBJECTIVE: It is known that total energy intake and its distribution during the
      day influences human anthropometric characteristics. However, possible
      association between variability in total energy intake and obesity has thus far
      remained unexamined. This study was designed to establish the influence of energy
      intake variability of each daily meal on the anthropometric characteristics of
      obesity. METHODS: A total of 521 individuals of Czech Caucasian origin aged 16-73
      years (390 women and 131 men) were included in the study, 7-day food records were
      completed by all study subjects and selected anthropometric characteristics were
      measured. The interquartile range (IQR) of energy intake was assessed
      individually for each meal of the day (as a marker of energy intake variability)
      and subsequently correlated with body mass index (BMI), body fat percentage
      (%BF), waist-hip ratio (WHR), and waist circumference (cW). RESULTS: Four
      distinct models were created using multiple logistic regression analysis and
      backward stepwise logistic regression. The most precise results, based on the
      area under the curve (AUC), were observed in case of the %BF model (AUC=0.895)
      and cW model (AUC=0.839). According to the %BF model, age (p<0.001) and IQR-lunch
      (p<0.05) seem to play an important prediction role for obesity. Likewise,
      according to the cW model, age (p<0.001), IQR-breakfast (p<0.05) and IQR-dinner
      (p <0.05) predispose patients to the development of obesity. The results of our
      study show that higher variability in the energy intake of key daily meals may
      increase the likelihood of obesity development. CONCLUSIONS: Based on the
      obtained results, it is necessary to emphasize the regularity in meals intake for
      maintaining proper body composition.

PMID- 29346859
TI  - Professor Vladimir Bencko Celebrates 80th Birthday.

PMID- 29346858
TI  - Comprehensive Group Therapy of Obesity and Its Impact on Selected Anthropometric
      and Postural Parameters.
AB  - OBJECTIVE: Obesity is a multifactorial disease. This non-infectious epidemic has
      reached pandemic proportions in the 21 century. Posture is a dynamic process
      referring to an active maintenance of body movement segments against the action
      of external forces. The aim of the study was to investigate the effect of
      comprehensive group therapy for obese persons on selected anthropometric and
      postural parameters. METHODS: The study comprised 53 females with a mean age of
      44.5 years (range 29-65 years, standard deviation 9.42 years, median 44 years),
      who completed a controlled weight loss programme. At the beginning and at the end
      of the programme, anthropometric parameters (Body Mass Index (BMI), weight and
      waist circumference) were measured and the posturography tests Limits of
      Stability (LOS) and Motor Control Test (MCT) were performed using the NeuroCom's
      SMART EquiTest system. The data were statistically analyzed using R software at a
      level of significance of 0.05. RESULTS: There were positive changes after the
      controlled weight loss programme in anthropometric parameters (BMI reduction,
      with p<0.001; waist circumference reduction, with p<0.001; and weight loss, with
      p<0.001), postural stability with statistically significant (p<0.05) improvements
      in both postural activity (LOS test parameters) and reactions (MCT parameters).
      CONCLUSION: The study showed a statistically significant effect of comprehensive
      group therapy for obesity in terms of reductions in waist circumference, body
      weight and BMI, and thus the overall reduction of both cardiovascular and
      metabolic risks, as well as improved postural skills (activity and reactions).

PMID- 29346860
TI  - Phase transitions between different spin-glass phases and between different
      chaoses in quenched random chiral systems.
AB  - The left-right chiral and ferromagnetic-antiferromagnetic double-spin-glass clock
      model, with the crucially even number of states q=4 and in three dimensions d=3,
      has been studied by renormalization-group theory. We find, for the first time to
      our knowledge, four spin-glass phases, including conventional, chiral, and
      quadrupolar spin-glass phases, and phase transitions between spin-glass phases.
      The chaoses, in the different spin-glass phases and in the phase transitions of
      the spin-glass phases with the other spin-glass phases, with the non-spin-glass
      ordered phases, and with the disordered phase, are determined and quantified by
      Lyapunov exponents. It is seen that the chiral spin-glass phase is the most
      chaotic spin-glass phase. The calculated phase diagram is also otherwise very
      rich, including regular and temperature-inverted devil's staircases and
      reentrances.

PMID- 29346861
TI  - Power series expansions for the planar monomer-dimer problem.
AB  - We compute the free energy of the planar monomer-dimer model. Unlike the
      classical planar dimer model, an exact solution is not known in this case. Even
      the computation of the low-density power series expansion requires heavy and
      nontrivial computations. Despite the exponential computational complexity, we
      compute almost three times more terms than were previously known. Such an
      expansion provides both lower and upper bounds for the free energy and makes it
      possible to obtain more accurate numerical values than previously possible. We
      expect that our methods can be applied to other similar problems.

PMID- 29346862
TI  - Craters produced by explosions in a granular medium.
AB  - We report on an experimental investigation of craters generated by explosions at
      the surface of a model granular bed. Following the initial blast, a pressure wave
      propagates through the bed, producing high-speed ejecta of grains and ultimately
      a crater. We analyzed the crater morphology in the context of large-scale
      explosions and other cratering processes. The process was analyzed in the context
      of large-scale explosions, and the crater morphology was compared with those
      resulting from other cratering processes in the same energy range. From this
      comparison, we deduce that craters formed through different mechanisms can
      exhibit fine surface features depending on their origin, at least at the
      laboratory scale. Moreover, unlike laboratory-scale craters produced by the
      impact of dense spheres, the diameter and depth do not follow a 1/4-power-law
      scaling with energy, rather the exponent observed herein is approximately 0.30,
      as has also been found in large-scale events. Regarding the ejecta curtain of
      grains, its expansion obeys the same time dependence followed by shock waves
      produced by underground explosions. Finally, from experiments in a two
      dimensional system, the early cavity growth is analyzed and compared to a recent
      study on explosions at the surface of water.

PMID- 29346863
TI  - Nucleation of twisted and tubular states in chiral ribbons.
AB  - Bilayers of chiral molecules can self-assemble into twisted and tubular
      structures, as was recently shown with chiral molecular constituents such as
      ssDNA-amphiphiles. I show that the dynamics of the transition between these
      topologies is driven by a nucleation mechanism that bears a striking formal
      similarity to that encountered in first-order wetting and dewetting transitions.
      Exploiting this analogy enables the critical nuclei of the transition to be
      calculated.

PMID- 29346864
TI  - Effects of particle-fluid density ratio on the interactions between the turbulent
      channel flow and finite-size particles.
AB  - A parallel direct-forcing fictitious domain method is employed to perform fully
      resolved numerical simulations of turbulent channel flow laden with finite-size
      particles. The effects of the particle-fluid density ratio on the turbulence
      modulation in the channel flow are investigated at the friction Reynolds number
      of 180, the particle volume fraction of 0.84%, and the particle-fluid density
      ratio ranging from 1 to 104.2. The results show that the variation of the flow
      drag with the particle-fluid density ratio is not monotonic, with a larger flow
      drag for the density ratio of 10.42, compared to those of unity and 104.2. A
      significant drag reduction by the particles is observed for large particle-fluid
      density ratios during the transient stage, but not at the statistically
      stationary stage. The intensity of particle velocity fluctuations generally
      decreases with increasing particle inertia, except that the particle streamwise
      root-mean-square velocity and streamwise-transverse velocity correlation in the
      near-wall region are largest at the density ratio of the order of 10. The
      averaged momentum equations are derived with the spatial averaging theorem and
      are used to analyze the mechanisms for the effects of the particles on the flow
      drag. The results indicate that the drag-reduction effect due to the decrease in
      the fluid Reynolds shear stress is counteracted by the drag-enhancement effect
      due to the increase in the total particle stress or the interphase drag force for
      the large particle-inertia case. The sum of the total Reynolds stress and
      particle inner stress contributions to the flow drag is largest at the density
      ratio of the order of 10, which is the reason for the largest flow drag at this
      density ratio. The interphase drag force obtained from the averaged momentum
      equation (the balance theory) is significantly smaller than (but agrees
      qualitatively with) that from the empirical drag formula based on the phase
      averaged slip velocity for large density ratios. For the neutrally buoyant case,
      the balance theory predicts a positive interphase force on the particles arising
      from the negative gradient of the particle inner stress, which cannot be
      predicted by the drag formula based on the phase-averaged slip velocity. In
      addition, our results show that both particle collision and particle-turbulence
      interaction play roles in the formation of the inhomogeneous distribution of the
      particles at the density ratio of the order of 10.

PMID- 29346865
TI  - Simplification of Markov chains with infinite state space and the mathematical
      theory of random gene expression bursts.
AB  - Here we develop an effective approach to simplify two-time-scale Markov chains
      with infinite state spaces by removal of states with fast leaving rates, which
      improves the simplification method of finite Markov chains. We introduce the
      concept of fast transition paths and show that the effective transitions of the
      reduced chain can be represented as the superposition of the direct transitions
      and the indirect transitions via all the fast transition paths. Furthermore, we
      apply our simplification approach to the standard Markov model of single-cell
      stochastic gene expression and provide a mathematical theory of random gene
      expression bursts. We give the precise mathematical conditions for the bursting
      kinetics of both mRNAs and proteins. It turns out that random bursts exactly
      correspond to the fast transition paths of the Markov model. This helps us gain a
      better understanding of the physics behind the bursting kinetics as an emergent
      behavior from the fundamental multiscale biochemical reaction kinetics of
      stochastic gene expression.

PMID- 29346866
TI  - Filter method without boundary-value condition for simultaneous calculation of
      eigenfunction and eigenvalue of a stationary Schrodinger equation on a grid.
AB  - The paper presents a method for simultaneous computation of eigenfunction and
      eigenvalue of the stationary Schrodinger equation on a grid, without imposing
      boundary-value condition. The method is based on the filter operator, which
      selects the eigenfunction from wave packet at the rate comparable to delta
      function. The efficacy and reliability of the method are demonstrated by
      comparing the simulation results with analytical or numerical solutions obtained
      by using other methods for various boundary-value conditions. It is found that
      the method is robust, accurate, and reliable. Further prospect of filter method
      for simulation of the Schrodinger equation in higher-dimensional space will also
      be highlighted.

PMID- 29346867
TI  - Two distinct bifurcation routes for delayed optoelectronic oscillators.
AB  - We investigate the coexistence of low- and high-frequency oscillations in a
      delayed optoelectronic oscillator. We identify two nearby Hopf bifurcation points
      exhibiting low and high frequencies and demonstrate analytically how they lead to
      stable solutions. We then show numerically that these two branches of solutions
      undergo higher order instabilities as the feedback rate is increased but remain
      separated in the bifurcation diagram. The two bifurcation routes can be followed
      independently by either progressively increasing or decreasing the bifurcation
      parameter.

PMID- 29346868
TI  - Effective one-dimensional approach to the source reconstruction problem of three
      dimensional inverse optoacoustics.
AB  - The direct problem of optoacoustic signal generation in biological media consists
      of solving an inhomogeneous three-dimensional (3D) wave equation for an initial
      acoustic stress profile. In contrast, the more defiant inverse problem requires
      the reconstruction of the initial stress profile from a proper set of observed
      signals. In this article, we consider an effectively 1D approach, based on the
      assumption of a Gaussian transverse irradiation source profile and plane acoustic
      waves, in which the effects of acoustic diffraction are described in terms of a
      linear integral equation. The respective inverse problem along the beam axis can
      be cast into a Volterra integral equation of the second kind for which we explore
      here efficient numerical schemes in order to reconstruct initial stress profiles
      from observed signals, constituting a methodical progress of computational
      aspects of optoacoustics. In this regard, we explore the validity as well as the
      limits of the inversion scheme via numerical experiments, with parameters geared
      toward actual optoacoustic problem instances. The considered inversion input
      consists of synthetic data, obtained in terms of the effectively 1D approach,
      and, more generally, a solution of the 3D optoacoustic wave equation. Finally, we
      also analyze the effect of noise and different detector-to-sample distances on
      the optoacoustic signal and the reconstructed pressure profiles.

PMID- 29346869
TI  - Brownian systems with spatially inhomogeneous activity.
AB  - We generalize the Green-Kubo approach, previously applied to bulk systems of
      spherically symmetric active particles [J. Chem. Phys. 145, 161101
      (2016)JCPSA60021-960610.1063/1.4966153], to include spatially inhomogeneous
      activity. The method is applied to predict the spatial dependence of the average
      orientation per particle and the density. The average orientation is given by an
      integral over the self part of the Van Hove function and a simple Gaussian
      approximation to this quantity yields an accurate analytical expression. Taking
      this analytical result as input to a dynamic density functional theory
      approximates the spatial dependence of the density in good agreement with
      simulation data. All theoretical predictions are validated using Brownian
      dynamics simulations.

PMID- 29346870
TI  - Nucleation and superstabilization in small systems.
AB  - Phase transitions are known to present peculiarities in small systems that are
      related to depletion effects of the ambient phase. Mass conservation affects the
      conditions of thermodynamic equilibrium between a nucleus of the new phase and
      the matrix as compared with nucleation in infinite systems. This finite-size
      effect is known to delay the phase transition but can also impede nucleation in
      very small systems as it stabilizes the initial state, originally metastable in
      infinite systems. In this work, we investigate this superstabilization effect in
      the context of classical nucleation theory in multicomponent solutions and we
      derive an analytical expression for the system size below which nucleation
      becomes thermodynamically impossible. Comparing with the exact solution, our
      simple result is shown to accurately predict the superstabilization effect, and
      can therefore be used, for instance, as a guideline for the design of novel
      nanomaterials.

PMID- 29346871
TI  - Electric-field-induced stretching of surface-tethered polyelectrolytes in a
      microchannel.
AB  - We study the stretching of a surface-tethered polyelectrolyte confined between
      parallel surfaces under the application of a dc electric field. We explore the
      influence of the electric-field strength, the length of the polyelectrolyte, and
      the degree of confinement on the conformation of the polyelectrolyte by single
      molecule experiments and coarse-grained coupled lattice-Boltzmann molecular
      dynamics simulations. The fractional extension of the polyelectrolyte is found to
      be a universal function of the product of the applied electric field and the
      molecular contour length, which is explained by simple scaling arguments. The
      degree of confinement does not have any significant influence on the stretching.
      We also confirm that an electrohydrodynamic equivalence principle relating the
      stretching in an electric field to that in a flow field is applicable.

PMID- 29346872
TI  - Border-crossing model for the diffusive coarsening of two-dimensional and quasi
      two-dimensional wet foams.
AB  - For dry foams, the transport of gas from small high-pressure bubbles to large low
      pressure bubbles is dominated by diffusion across the thin soap films separating
      neighboring bubbles. For wetter foams, the film areas become smaller as the
      Plateau borders and vertices inflate with liquid. So-called "border-blocking"
      models can explain some features of wet-foam coarsening based on the presumption
      that the inflated borders totally block the gas flux; however, this approximation
      dramatically fails in the wet or unjamming limit where the bubbles become close
      packed spheres and coarsening proceeds even though there are no films. Here, we
      account for the ever-present border-crossing flux by a new length scale defined
      by the average gradient of gas concentration inside the borders. We compute that
      it is proportional to the geometric average of film and border thicknesses, and
      we verify this scaling by numerical solution of the diffusion equation. We
      similarly consider transport across inflated vertices and surface Plateau borders
      in quasi-two-dimensional foams. And we show how the dA/dt=K_{0}(n-6) von Neumann
      law is modified by the appearance of terms that depend on bubble size and shape
      as well as the concentration gradient length scales. Finally, we use the modified
      von Neumann law to compute the growth rate of the average bubble area, which is
      not constant.

PMID- 29346873
TI  - Autonomously responsive pumping by a bacterial flagellar forest: A mean-field
      approach.
AB  - This study is motivated by a microfluidic device that imparts a magnetic torque
      on an array of bacterial flagella. Bacterial flagella can transform their helical
      geometry autonomously in response to properties of the background fluid, which
      provides an intriguing mechanism allowing their use as an engineered element for
      the regulation or transport of chemicals in microscale applications. The
      synchronization of flagellar phase has been widely studied in biological
      contexts, but here we examine the synchronization of flagellar tilt, which is
      necessary for effective pumping. We first examine the effects of helical geometry
      and tilt on the pumping flows generated by a single rotating flagellum. Next, we
      explore a mean-field model for an array of helical flagella to understand how
      collective tilt arises and influences pumping. The mean-field methodology allows
      us to take into account possible phase differences through a time-averaging
      procedure and to model an infinite array of flagella. We find array separation
      distances, magnetic field strengths, and rotation frequencies that produce
      nontrivial self-consistent pumping solutions. For individual flagella, pumping is
      reversed when helicity or rotation is reversed; in contrast, when collective
      effects are included, self-consistent tilted pumping solutions become untilted
      nonpumping solutions when helicity or rotation is reversed.

PMID- 29346874
TI  - Internal autoresonance in coupled oscillators with slowly decaying frequency.
AB  - In this work, we study resonance energy transfer from an impulsively loaded
      strongly nonlinear oscillator to a weakly coupled linear attachment with a slowly
      time-decaying stiffness. It is shown that even in the absence of external
      periodic forcing both oscillators may exhibit the resonance phenomenon, with the
      permanent response enhancement of the linear oscillator and the corresponding
      response reduction of the nonlinear actuator. This effect is said to be internal
      autoresonance. The influence of the system parameters on the emergence and
      stability of autoresonance is investigated both analytically and numerically.

PMID- 29346875
TI  - Granular temperature measured experimentally in a shear flow by acoustic energy.
AB  - Granular temperature may control high-speed granular flows, yet it is difficult
      to measure in laboratory experiments. Here we utilize acoustic energy to measure
      granular temperature in dense shear flows. We show that acoustic energy captures
      the anticipated behavior of granular temperature as a function of grain size in
      quartz sand shear flows. We also find that granular temperature (through its
      proxy acoustic energy) is nearly linearly proportional to inertial number, and
      dilation is proportional to acoustic energy raised to the power 0.6+/-0.2. This
      demonstrates the existence of a relationship between granular temperature and
      dilation. It is also consistent with previous results on dilation due to
      externally imposed vibration, thus showing that internally and externally induced
      vibrations have identical results on granular shear flows.

PMID- 29346876
TI  - X-ray scattering reveals molecular tilt is an order parameter for the main phase
      transition in a model biomembrane.
AB  - Synchrotron diffuse x-ray scattering data reveal a dramatic softening of the
      molecular tilt modulus K_{theta} of the model biomembrane composed of DMPC lipids
      as the temperature is lowered towards the main phase transition temperature at
      T_{M}=24^{?}C. Spontaneous tilt occurs below T_{M}, suggesting that tilt is a
      symmetry breaking order parameter. Consistent with this hypothesis, it is also
      found that a different lipid POPS has no spontaneous tilt below its T_{M} at
      14^{?}C and correspondingly its tilt modulus did not soften as T_{M} was
      approached from above. As previously known, the bending modulus K_{C} of DMPC
      also softens close to T_{M}, but unlike the tilt modulus, K_{C} has a maximum
      3^{?} above T_{M}, which also marks the limit of the well-known anomalous
      swelling regime. Tilt adds a different perspective to our previous understanding
      of the main phase transition in lipid bilayers.

PMID- 29346877
TI  - Stable three-dimensional modon soliton in plasmas.
AB  - We derive the nonlinear equations that describe coupled drift waves and ion
      acoustic waves in a plasma. We show that when the coupling to ion acoustic waves
      is negligible, the reduced nonlinear equation is a generalization of the Hasegawa
      Mima equation to the three-dimensional (3D) case. We find an exact analytical
      solution of this equation in the form of a 3D soliton drift wave (3D modon). By
      numerical simulations we study collisions between the modons and show that the
      collisions can be fully elastic.

PMID- 29346878
TI  - Publisher's Note: Golf-course and funnel energy landscapes: Protein folding
      concepts in martensites [Phys. Rev. E 95, 063003 (2017)].
AB  - This corrects the article DOI: 10.1103/PhysRevE.95.063003.

PMID- 29346879
TI  - Phase behavior of binary and polydisperse suspensions of compressible microgels
      controlled by selective particle deswelling.
AB  - We investigate the phase behavior of suspensions of poly(N-isopropylacrylamide)
      (pNIPAM) microgels with either bimodal or polydisperse size distribution. We
      observe a shift of the fluid-crystal transition to higher concentrations
      depending on the polydispersity or the fraction of large particles in suspension.
      Crystallization is observed up to polydispersities as high as 18.5%, and up to a
      number fraction of large particles of 29% in bidisperse suspensions. The crystal
      structure is random hexagonal close-packed as in monodisperse pNIPAM microgel
      suspensions. We explain our experimental results by considering the effect of
      bound counterions. Above a critical particle concentration, these cause
      deswelling of the largest microgels, which are the softest, changing the size
      distribution of the suspension and enabling crystal formation in conditions where
      incompressible particles would not crystallize.

PMID- 29346880
TI  - Emergence and detailed structure of terraced surfaces produced by oblique
      incidence ion sputtering.
AB  - We study the nanoscale terraced topographies that arise when a solid surface is
      bombarded with a broad ion beam that has a relatively high angle of incidence
      theta. We find that the surface is not completely flat between the regions in
      which the surface slope changes rapidly with position: Instead, small-amplitude
      ripples propagate along the surface. Our analytical work on these ripples yields
      their propagation velocity as well as the scaling behavior of their amplitude.
      Our simulations establish that the surfaces exhibit interrupted coarsening, i.e.,
      the characteristic width and height of the surface disturbance grow for a time
      but ultimately asymptote to finite values as the fully terraced state develops.
      In addition, as theta is reduced, the surface can undergo a transition from a
      terraced morphology that changes little with time as it propagates over the
      surface to an unterraced state that appears to exhibit spatiotemporal chaos. For
      different ranges of the parameters, our equation of motion produces unterraced
      topographies that are remarkably similar to those seen in various experiments,
      including pyramidal structures that are elongated along the projected beam
      direction and isolated lenticular depressions.

PMID- 29346881
TI  - Coda reconstruction from cross-correlation of a diffuse field on thin elastic
      plates.
AB  - This study contributes to the evaluation of the robustness and accuracy of
      Green's function reconstruction from cross-correlation of strongly dispersed
      reverberated signals, with disentangling of the respective roles of ballistic and
      reverberated ("coda") contributions. We conduct a suite of experiments on a
      highly reverberating thin duralumin plate, where an approximately diffuse
      flexural wave field is generated by taking advantage of the plate reverberation
      and wave dispersion. A large number of impulsive sources that cover the whole
      surface of the plate are used to validate ambient-noise theory through comparison
      of the causal and anticausal (i.e., positive- and negative-time) terms of the
      cross-correlation to one another and to the directly measured Green's function.
      To quantify the contribution of the ballistic and coda signals, the cross
      correlation integral is defined over different time windows of variable length,
      and the accuracy of the reconstructed Green's function is studied as a function
      of the initial and end times of the integral. We show that even cross
      correlations measured over limited time windows converge to a significant part of
      the Green's function. Convergence is achieved over a wide time window, which
      includes not only direct flexural-wave arrivals, but also the multiply
      reverberated coda. We propose a model, based on normal-mode analysis, that
      relates the similarity between the cross-correlation and the Green's function to
      the statistical properties of the plate. We also determine quantitatively how
      incoherent noise degrades the estimation of the Green's function.

PMID- 29346882
TI  - Morphological-evolution pathway during phase separation in polymer solutions with
      highly asymmetrical miscibility gap.
AB  - Microstructural evolution during thermally induced phase separation in a polymer
      solution with a highly asymmetrical miscibility gap is analyzed using Flory
      Huggins thermodynamics and nonlinear Cahn-Hilliard kinetics. Computer simulation
      results demonstrate that, in contrast to systems with symmetric miscibility gaps,
      interesting morphological-evolution pathways (MEPs) including cluster-to
      percolation and percolation-to-cluster transitions are identified. These MEPs are
      rationalized according to asynchronous evolution of the two product phases. For a
      highly asymmetric polymer system, the initial solution composition is also found
      to play a critical role in determining the MEPs. According to the simulation
      results a map of MEPs in terms of initial solution composition and aging time of
      phase separation is established to guide future microstructural design in
      asymmetrical polymer solutions.

PMID- 29346883
TI  - Force spectroscopy unravels the role of ionic strength on DNA-cisplatin
      interaction: Modulating the binding parameters.
AB  - In the present work we have gone a step forward in the understanding of the DNA
      cisplatin interaction, investigating the role of the ionic strength on the
      complexes formation. To achieve this task, we use optical tweezers to perform
      force spectroscopy on the DNA-cisplatin complexes, determining their mechanical
      parameters as a function of the drug concentration in the sample for three
      different buffers. From such measurements, we determine the binding parameters
      and study their behavior as a function of the ionic strength. The equilibrium
      binding constant decreases with the counterion concentration ([Na]) and can be
      used to estimate the effective net charge of cisplatin in solution. The
      cooperativity degree of the binding reaction, on the other hand, increases with
      the ionic strength, as a result of the different conformational changes induced
      by the drug on the double-helix when binding under different buffer conditions.
      Such results can be used to modulate the drug binding to DNA, by appropriately
      setting the ionic strength of the surrounding buffer. The conclusions drawn
      provide significant new insights on the complex cooperative interactions between
      the DNA molecule and the class of platinum-based compounds, much used in
      chemotherapies.

PMID- 29346884
TI  - Nonstationary dynamics of encounters: Mean valuable territory covered by a random
      searcher.
AB  - Inspired by recent experiments on the organism Caenorhabditis elegans we present
      a stochastic problem to capture the adaptive dynamics of search in living beings,
      which involves the exploration-exploitation dilemma between remaining in a
      previously preferred area and relocating to new places. We assess the question of
      search efficiency by introducing a new magnitude, the mean valuable territory
      covered by a Browinan searcher, for the case where each site in the domain
      becomes valuable only after a random time controlled by a nonhomogeneous rate
      which expands from the origin outwards. We explore analytically this magnitude
      for domains of dimensions 1, 2, and 3 and discuss the theoretical and applied
      (biological) interest of our approach. As the main results here, we (i) report
      the existence of some universal scaling properties for the mean valuable
      territory covered as a function of time and (ii) reveal the emergence of an
      optimal diffusivity which appears only for domains in two and higher dimensions.

PMID- 29346885
TI  - Theoretical microbial ecology without species.
AB  - Ecosystems are commonly conceptualized as networks of interacting species.
      However, partitioning natural diversity of organisms into discrete units is
      notoriously problematic and mounting experimental evidence raises the intriguing
      question whether this perspective is appropriate for the microbial world. Here an
      alternative formalism is proposed that does not require postulating the existence
      of species as fundamental ecological variables and provides a naturally
      hierarchical description of community dynamics. This formalism allows approaching
      the species problem from the opposite direction. While the classical models treat
      a world of imperfectly clustered organism types as a perturbation around well
      clustered species, the presented approach allows gradually adding structure to a
      fully disordered background. The relevance of this theoretical construct for
      describing highly diverse natural ecosystems is discussed.

PMID- 29346886
TI  - Predictability of escape for a stochastic saddle-node bifurcation: When rare
      events are typical.
AB  - Transitions between multiple stable states of nonlinear systems are ubiquitous in
      physics, chemistry, and beyond. Two types of behaviors are usually seen as
      mutually exclusive: unpredictable noise-induced transitions and predictable
      bifurcations of the underlying vector field. Here, we report a different
      situation, corresponding to a fluctuating system approaching a bifurcation, where
      both effects collaborate. We show that the problem can be reduced to a single
      control parameter governing the competition between deterministic and stochastic
      effects. Two asymptotic regimes are identified: When the control parameter is
      small (e.g., small noise), deviations from the deterministic case are well
      described by the Freidlin-Wentzell theory. In particular, escapes over the
      potential barrier are very rare events. When the parameter is large (e.g., large
      noise), such events become typical. Unlike pure noise-induced transitions, the
      distribution of the escape time is peaked around a value which is asymptotically
      predicted by an adiabatic approximation. We show that the two regimes are
      characterized by qualitatively different reacting trajectories with algebraic and
      exponential divergences, respectively.

PMID- 29346887
TI  - Time correlation functions in the Lebwohl-Lasher model of liquid crystals.
AB  - Time correlation functions in the Lebwohl-Lasher model of nematic liquid crystals
      are studied using theory and molecular dynamics simulations. In particular, the
      autocorrelation functions of angular momentum and nematic director fluctuations
      are calculated in the long-wavelength limit. The constitutive relations for the
      hydrodynamic currents are derived using a standard procedure based on non
      negativity of the entropy production. The continuity equations are then
      linearized and solved to calculate the correlation functions. We find that the
      transverse angular momentum fluctuations are coupled to the director fluctuations
      and are both propagative. The propagative nature of the fluctuations suppresses
      the anticipated hydrodynamic long-time tails in the single-particle
      autocorrelation functions. The fluctuations in the isotropic phase are, however,
      diffusive, leading to t^{-d/2} long-time tails in d spatial dimensions. The Frank
      elastic constant measured using the time correlation functions are in good
      agreement with previously reported results.

PMID- 29346888
TI  - Critical adsorption profiles around a sphere and a cylinder in a fluid at
      criticality: Local functional theory.
AB  - We study universal critical adsorption on a solid sphere and a solid cylinder in
      a fluid at bulk criticality, where preferential adsorption occurs. We use a local
      functional theory proposed by Fisher et al. [M. E. Fisher and P. G. de Gennes, C.
      R. Acad. Sci. Paris Ser. B 287, 207 (1978); M. E. Fisher and H. Au-Yang, Physica
      A 101, 255 (1980)PHYADX0378-437110.1016/0378-4371(80)90112-0]. We calculate the
      mean order parameter profile psi(r), where r is the distance from the sphere
      center and the cylinder axis, respectively. The resultant differential equation
      for psi(r) is solved exactly around a sphere and numerically around a cylinder. A
      strong adsorption regime is realized except for very small surface field h_{1},
      where the surface order parameter psi(a) is determined by h_{1} and is
      independent of the radius a. If r considerably exceeds a, psi(r) decays as r^{
      (1+eta)} for a sphere and r^{-(1+eta)/2} for a cylinder in three dimensions,
      where eta is the critical exponent in the order parameter correlation at bulk
      criticality.

PMID- 29346889
TI  - Morphological inversion of complex diffusion.
AB  - Epidemics, neural cascades, power failures, and many other phenomena can be
      described by a diffusion process on a network. To identify the causal origins of
      a spread, it is often necessary to identify the triggering initial node. Here, we
      define a new morphological operator and use it to detect the origin of a
      diffusive front, given the final state of a complex network. Our method performs
      better than algorithms based on distance (closeness) and Jordan centrality. More
      importantly, our method is applicable regardless of the specifics of the forward
      model, and therefore can be applied to a wide range of systems such as
      identifying the patient zero in an epidemic, pinpointing the neuron that triggers
      a cascade, identifying the original malfunction that causes a catastrophic
      infrastructure failure, and inferring the ancestral species from which a
      heterogeneous population evolves.

PMID- 29346890
TI  - Mechanics of active surfaces.
AB  - We derive a fully covariant theory of the mechanics of active surfaces. This
      theory provides a framework for the study of active biological or chemical
      processes at surfaces, such as the cell cortex, the mechanics of epithelial
      tissues, or reconstituted active systems on surfaces. We introduce forces and
      torques acting on a surface, and derive the associated force balance conditions.
      We show that surfaces with in-plane rotational symmetry can have broken up-down,
      chiral, or planar-chiral symmetry. We discuss the rate of entropy production in
      the surface and write linear constitutive relations that satisfy the Onsager
      relations. We show that the bending modulus, the spontaneous curvature, and the
      surface tension of a passive surface are renormalized by active terms. Finally,
      we identify active terms which are not found in a passive theory and discuss
      examples of shape instabilities that are related to active processes in the
      surface.

PMID- 29346891
TI  - Discrete-to-continuum modeling of weakly interacting incommensurate chains.
AB  - In this paper we use a formal discrete-to-continuum procedure to derive a
      continuum variational model for two chains of atoms with slightly incommensurate
      lattices. The chains represent a cross section of a three-dimensional system
      consisting of a graphene sheet suspended over a substrate. The continuum model
      recovers both qualitatively and quantitatively the behavior observed in the
      corresponding discrete model. The numerical solutions for both models demonstrate
      the presence of large commensurate regions separated by localized incommensurate
      domain walls.

PMID- 29346892
TI  - Anomalous stress fluctuations in athermal two-dimensional amorphous solids.
AB  - We numerically study the local stress distribution within athermal, isotropically
      stressed, mechanically stable, packings of bidisperse frictionless disks above
      the jamming transition in two dimensions. Considering the Fourier transform of
      the local stress, we find evidence for algebraically increasing fluctuations in
      both isotropic and anisotropic components of the stress tensor at small wave
      numbers, contrary to recent theoretical predictions. Such increasing fluctuations
      imply a lack of self-averaging of the stress on large length scales. The
      crossover to these increasing fluctuations defines a length scale l_{0}, however,
      it appears that l_{0} does not vary much with packing fraction phi, nor does
      l_{0} seem to be diverging as phi approaches the jamming phi_{J}. We also find
      similar large length scale fluctuations of stress in the inherent states of a
      quenched Lennard-Jones liquid, leading us to speculate that such fluctuations may
      be a general property of amorphous solids in two dimensions.

PMID- 29346893
TI  - Resuspension threshold of a granular bed by localized heating.
AB  - The resuspension and dispersion of particles occur in industrial fluid dynamic
      processes as well as environmental and geophysical situations. In this paper, we
      experimentally investigate the ability to fluidize a granular bed with a vertical
      gradient of temperature. Using laboratory experiments with a localized heat
      source, we observe a large entrainment of particles into the fluid volume beyond
      a threshold temperature. The buoyancy-driven fluidized bed then leads to the
      transport of solid particles through the generation of particle-laden plumes. We
      show that the destabilization process is driven by the thermal conductivity
      inside the granular bed and demonstrate that the threshold temperature depends on
      the thickness of the granular bed and the buoyancy number, i.e., the ratio of the
      stabilizing density contrast to the destabilizing thermal density contrast.

PMID- 29346894
TI  - Size scaling of failure strength with fat-tailed disorder in a fiber bundle
      model.
AB  - We investigate the size scaling of the macroscopic fracture strength of
      heterogeneous materials when microscopic disorder is controlled by fat-tailed
      distributions. We consider a fiber bundle model where the strength of single
      fibers is described by a power law distribution over a finite range. Tuning the
      amount of disorder by varying the power law exponent and the upper cutoff of
      fibers' strength, in the limit of equal load sharing an astonishing size effect
      is revealed: For small system sizes the bundle strength increases with the number
      of fibers, and the usual decreasing size effect of heterogeneous materials is
      restored only beyond a characteristic size. We show analytically that the extreme
      order statistics of fibers' strength is responsible for this peculiar behavior.
      Analyzing the results of computer simulations we deduce a scaling form which
      describes the dependence of the macroscopic strength of fiber bundles on the
      parameters of microscopic disorder over the entire range of system sizes.

PMID- 29346895
TI  - Levy walks in nonhomogeneous environments.
AB  - The Levy walk process with rests is discussed. The jumping time is governed by an
      alpha-stable distribution with alpha>1 while a waiting time distribution is
      Poissonian and involves a position-dependent rate which reflects a nonhomogeneous
      trap distribution. The master equation is derived and solved in the asymptotic
      limit for a power-law form of the jumping rate. The relative density of resting
      and flying particles appears time-dependent, and the asymptotic form of both
      distributions obeys a stretched-exponential shape at large time. The diffusion
      properties are discussed, and it is demonstrated that, due to the heterogeneous
      trap structure, the enhanced diffusion, observed for the homogeneous case, may
      turn to a subdiffusion. The density distributions and mean squared displacements
      are also evaluated from Monte Carlo simulations of individual trajectories.

PMID- 29346896
TI  - Nonequilibrium thermodynamics with binary quantum correlations.
AB  - The balance equations for thermodynamic quantities are derived from the nonlocal
      quantum kinetic equation. The nonlocal collisions lead to molecular contributions
      to the observables and currents. The corresponding correlated parts of the
      observables are found to be given by the rate to form a molecule multiplied with
      its lifetime which can be considered as collision duration. Explicit expressions
      of these molecular contributions are given in terms of the scattering phase
      shifts. The two-particle form of the entropy is derived extending the Landau
      quasiparticle picture by two-particle molecular contributions. There is a
      continuous exchange of correlation and kinetic energies condensing into the rate
      of correlated variables for energy and momentum. For the entropy, an explicit
      gain remains and Boltzmann's H theorem is proved including the molecular parts of
      the entropy.

PMID- 29346897
TI  - Quantum Otto engine with exchange coupling in the presence of level degeneracy.
AB  - We consider a quasistatic quantum Otto cycle using two effectively two-level
      systems with degeneracy in the excited state. The systems are coupled through
      isotropic exchange interaction of strength J>0, in the presence of an external
      magnetic field B which is varied during the cycle. We prove the positive work
      condition and show that level degeneracy can act as a thermodynamic resource, so
      that a larger amount of work can be extracted than in the nondegenerate case,
      both with and without coupling. We also derive an upper bound for the efficiency
      of the cycle. This bound is the same as derived for a system of coupled spin-1/2
      particles [G. Thomas and R. S. Johal, Phys. Rev. E 83, 031135 (2011)PLEEE81539
      375510.1103/PhysRevE.83.031135], i.e., without degeneracy, and depends only on
      the control parameters of the Hamiltonian, being independent of the level
      degeneracy and the reservoir temperatures.

PMID- 29346898
TI  - Stochastic Kuramoto oscillators with discrete phase states.
AB  - We present a generalization of the Kuramoto phase oscillator model in which
      phases advance in discrete phase increments through Poisson processes, rendering
      both intrinsic oscillations and coupling inherently stochastic. We study the
      effects of phase discretization on the synchronization and precision properties
      of the coupled system both analytically and numerically. Remarkably, many key
      observables such as the steady-state synchrony and the quality of oscillations
      show distinct extrema while converging to the classical Kuramoto model in the
      limit of a continuous phase. The phase-discretized model provides a general
      framework for coupled oscillations in a Markov chain setting.

PMID- 29346899
TI  - Formation and relaxation of quasistationary states in particle systems with power
      law interactions.
AB  - We explore the formation and relaxation of the so-called quasistationary states
      (QSS) for particle distributions in three dimensions interacting via an
      attractive radial pair potential V(r->infinity)~1/r^{gamma} with gamma>0, and
      either a soft core or hard core regularization at small r. In the first part of
      the paper, we generalize, for any spatial dimension d>=2, Chandrasekhar's
      approach for the case of gravity to obtain analytic estimates of the rate of
      collisional relaxation due to two-body collisions. The resultant relaxation rates
      indicate an essential qualitative difference depending on the integrability of
      the pair force at large distances: for gamma>d-1, the rate diverges in the large
      particle number N (mean-field) limit, unless a sufficiently large soft core is
      present; for gamma<d-1, on the other hand, the rate vanishes in the same limit
      even in the absence of any regularization. In the second part of the paper we
      compare our analytical predictions with the results of extensive parallel
      numerical simulations in d=3 performed with an appropriate modification of the
      gadget code, for a range of different exponents gamma and soft cores leading to
      the formation of QSS. We find, just as for the previously well studied case of
      gravity (which we also revisit), excellent agreement between the parametric
      dependence of the observed relaxation times and our analytic predictions.
      Further, as in the case of gravity, we find that the results indicate that, when
      large impact factors dominate, the appropriate cutoff is the size of the system
      (rather than, for example, the mean interparticle distance). Our results provide
      strong evidence that the existence of QSS is robust only for long-range
      interactions with a large distance behavior gamma<d-1; for gamma>=d-1, the
      existence of such states will be conditioned strongly on the short-range
      properties of the interaction.

PMID- 29346900
TI  - Smoothed particle hydrodynamics study of the roughness effect on contact angle
      and droplet flow.
AB  - We employ a pairwise force smoothed particle hydrodynamics (PF-SPH) model to
      simulate sessile and transient droplets on rough hydrophobic and hydrophilic
      surfaces. PF-SPH allows modeling of free-surface flows without discretizing the
      air phase, which is achieved by imposing the surface tension and dynamic contact
      angles with pairwise interaction forces. We use the PF-SPH model to study the
      effect of surface roughness and microscopic contact angle on the effective
      contact angle and droplet dynamics. In the first part of this work, we
      investigate static contact angles of sessile droplets on different types of rough
      surfaces. We find that the effective static contact angles of Cassie and Wenzel
      droplets on a rough surface are greater than the corresponding microscale static
      contact angles. As a result, microscale hydrophobic rough surfaces also show
      effective hydrophobic behavior. On the other hand, microscale hydrophilic
      surfaces may be macroscopically hydrophilic or hydrophobic, depending on the type
      of roughness. We study the dependence of the transition between Cassie and Wenzel
      states on roughness and droplet size, which can be linked to the critical
      pressure for the given fluid-substrate combination. We observe good agreement
      between simulations and theoretical predictions. Finally, we study the impact of
      the roughness orientation (i.e., an anisotropic roughness) and surface
      inclination on droplet flow velocities. Simulations show that droplet flow
      velocities are lower if the surface roughness is oriented perpendicular to the
      flow direction. If the predominant elements of surface roughness are in alignment
      with the flow direction, the flow velocities increase compared to smooth
      surfaces, which can be attributed to the decrease in fluid-solid contact area
      similar to the lotus effect. We demonstrate that classical linear scaling
      relationships between Bond and capillary numbers for droplet flow on flat
      surfaces also hold for flow on rough surfaces.

PMID- 29346901
TI  - Method of model reduction and multifidelity models for solute transport in random
      layered porous media.
AB  - This work presents a method of model reduction that leads to models with three
      solutions of increasing fidelity (multifidelity models) for solute transport in a
      bounded layered porous media with random permeability. The model generalizes the
      Taylor-Aris dispersion theory to stochastic transport in random layered porous
      media with a known velocity covariance function. In the reduced model, we
      represent (random) concentration in terms of its cross-sectional average and a
      variation function. We derive a one-dimensional stochastic advection-dispersion
      type equation for the average concentration and a stochastic Poisson equation for
      the variation function, as well as expressions for the effective velocity and
      dispersion coefficient. In contrast to the linear scaling with the correlation
      length and the mean velocity from macrodispersion theory, our model predicts a
      nonlinear and a quadratic dependence of the effective dispersion on the
      correlation length and the mean velocity, respectively. We observe that velocity
      fluctuations enhance dispersion in a nonmonotonic fashion (a stochastic spike
      phenomenon): The dispersion initially increases with correlation length lambda,
      reaches a maximum, and decreases to zero at infinity (correlation). Maximum
      enhancement in dispersion can be obtained at a correlation length about 0.25 the
      size of the porous media perpendicular to flow. This information can be useful
      for engineering such random layered porous media. Numerical simulations are
      implemented to compare solutions with varying fidelity.

PMID- 29346902
TI  - Transport, diffusion, and energy studies in the Arnold-Beltrami-Childress map.
AB  - We study the transport and diffusion properties of passive inertial particles
      described by a six-dimensional dissipative bailout embedding map. The base map
      chosen for the study is the three-dimensional incompressible Arnold-Beltrami
      Childress (ABC) map chosen as a representation of volume preserving flows. There
      are two distinct cases: the two-action and the one-action cases, depending on
      whether two or one of the parameters (A,B,C) exceed 1. The embedded map dynamics
      is governed by two parameters (alpha,gamma), which quantify the mass density
      ratio and dissipation, respectively. There are important differences between the
      aerosol (alpha<1) and the bubble (alpha>1) regimes. We have studied the diffusive
      behavior of the system and constructed the phase diagram in the parameter space
      by computing the diffusion exponents eta. Three classes have been broadly
      classified-subdiffusive transport (eta<1), normal diffusion (eta~1), and
      superdiffusion (eta>1) with eta~2 referred to as the ballistic regime.
      Correlating the diffusive phase diagram with the phase diagram for dynamical
      regimes seen earlier, we find that the hyperchaotic bubble regime is largely
      correlated with normal and superdiffusive behavior. In contrast, in the aerosol
      regime, ballistic superdiffusion is seen in regions that largely show periodic
      dynamical behaviors, whereas subdiffusive behavior is seen in both periodic and
      chaotic regimes. The probability distributions of the diffusion exponents show
      power-law scaling for both aerosol and bubbles in the superdiffusive regimes. We
      further study the Poincare recurrence times statistics of the system. Here, we
      find that recurrence time distributions show power law regimes due to the
      existence of partial barriers to transport in the phase space. Moreover, the plot
      of average particle kinetic energies versus the mass density ratio for the two
      action case exhibits a devil's staircase-like structure for higher dissipation
      values. We explain these results and discuss their implications for realistic
      systems.

PMID- 29346903
TI  - Pseudospectral Maxwell solvers for an accurate modeling of Doppler harmonic
      generation on plasma mirrors with particle-in-cell codes.
AB  - With the advent of petawatt class lasers, the very large laser intensities
      attainable on target should enable the production of intense high-order Doppler
      harmonics from relativistic laser-plasma mirror interactions. At present, the
      modeling of these harmonics with particle-in-cell (PIC) codes is extremely
      challenging as it implies an accurate description of tens to hundreds of harmonic
      orders on a broad range of angles. In particular, we show here that due to the
      numerical dispersion of waves they induce in vacuum, standard finite difference
      time domain (FDTD) Maxwell solvers employed in most PIC codes can induce a
      spurious angular deviation of harmonic beams potentially degrading simulation
      results. This effect was extensively studied and a simple toy model based on the
      Snell-Descartes law was developed that allows us to finely predict the angular
      deviation of harmonics depending on the spatiotemporal resolution and the Maxwell
      solver used in the simulations. Our model demonstrates that the mitigation of
      this numerical artifact with FDTD solvers mandates very high spatiotemporal
      resolution preventing realistic three-dimensional (3D) simulations even on the
      largest computers available at the time of writing. We finally show that
      nondispersive pseudospectral analytical time domain solvers can considerably
      reduce the spatiotemporal resolution required to mitigate this spurious deviation
      and should enable in the near future 3D accurate modeling on supercomputers in a
      realistic time to solution.

PMID- 29346904
TI  - Extracting oscillating components from nonstationary time series: A wavelet
      induced method.
AB  - This paper consists in the description and application of a method called wavelet
      induced mode extraction (WIME) in the context of time-frequency analysis. WIME
      aims to extract the oscillating components that build amplitude modulated
      frequency modulated signals. The essence of this technique relies on the
      successive extractions of the dominant ridges of wavelet-based time-frequency
      representations of the signal under consideration. Our tests on simulated
      examples indicate strong decomposition and reconstruction skills, trouble-free
      handling of crossing trajectories in the time-frequency plane, sharp performances
      in frequency detection in the case of mode-mixing problems, and a natural
      tolerance to noise. These results are compared with those obtained with empirical
      mode decomposition. We also show that WIME still gives meaningful results with
      real-life data, namely, the Oceanic Nino Index.

PMID- 29346905
TI  - Predicting Escherichia coli's chemotactic drift under exponential gradient.
AB  - Bacterial species are known to show chemotaxis, i.e., the directed motions in the
      presence of certain chemicals, whereas the motion is random in the absence of
      those chemicals. The bacteria modulate their run time to induce chemotactic drift
      towards the attractant chemicals and away from the repellent chemicals. However,
      the existing theoretical knowledge does not exhibit a proper match with
      experimental validation, and hence there is a need for developing alternate
      models and validating experimentally. In this paper a more robust theoretical
      model is proposed to investigate chemotactic drift of peritrichous Escherichia
      coli under an exponential nutrient gradient. An exponential gradient is used to
      understand the steady state behavior of drift because of the logarithmic
      functionality of the chemosensory receptors. Our theoretical estimations are
      validated through the experimentation and simulation results. Thus, the developed
      model successfully delineates the run time, run trajectory, and drift velocity as
      measured from the experiments.

PMID- 29346906
TI  - Smoothed particle hydrodynamics method for evaporating multiphase flows.
AB  - The smoothed particle hydrodynamics (SPH) method has been increasingly used for
      simulating fluid flows; however, its ability to simulate evaporating flow
      requires significant improvements. This paper proposes an SPH method for
      evaporating multiphase flows. The present SPH method can simulate the heat and
      mass transfers across the liquid-gas interfaces. The conservation equations of
      mass, momentum, and energy were reformulated based on SPH, then were used to
      govern the fluid flow and heat transfer in both the liquid and gas phases. The
      continuity equation of the vapor species was employed to simulate the vapor mass
      fraction in the gas phase. The vapor mass fraction at the interface was predicted
      by the Clausius-Clapeyron correlation. An evaporation rate was derived to predict
      the mass transfer from the liquid phase to the gas phase at the interface.
      Because of the mass transfer across the liquid-gas interface, the mass of an SPH
      particle was allowed to change. Alternative particle splitting and merging
      techniques were developed to avoid large mass difference between SPH particles of
      the same phase. The proposed method was tested by simulating three problems,
      including the Stefan problem, evaporation of a static drop, and evaporation of a
      drop impacting a hot surface. For the Stefan problem, the SPH results of the
      evaporation rate at the interface agreed well with the analytical solution. For
      drop evaporation, the SPH result was compared with the result predicted by a
      level-set method from the literature. In the case of drop impact on a hot
      surface, the evolution of the shape of the drop, temperature, and vapor mass
      fraction were predicted.

PMID- 29346907
TI  - Fast electrons generated by quasistatic electric fields of a fs-laser-pulse
      induced plasma.
AB  - We present a new acceleration mechanism for electrons taking place during the
      interaction of an ultrashort, nonrelativistic laser pulse with a plasma generated
      at the surface of a solid density target. In our experiments, the plasma is
      created by a laser pulse with femtosecond duration and an energy of about 1 mJ
      focused to intensities of above 10^{17}W/cm^{2}. We observe that the electron
      energies acquired by this mechanism exceed the ponderomotive potential of the
      laser by an order of magnitude. This result was reproduced and quantitatively
      confirmed by particle-in-cell simulations, which further revealed that the
      observed electron acceleration is based on quasistatic electric fields caused by
      the space charges of ponderomotively preaccelerated electrons. This acceleration
      process is examined in more detail by a simplified numerical model, which allows
      a qualitative explanation of the final electron energies.

PMID- 29346908
TI  - Mechanisms of self-organized criticality in social processes of knowledge
      creation.
AB  - In online social dynamics, a robust scale invariance appears as a key feature of
      collaborative efforts that lead to new social value. The underlying empirical
      data thus offers a unique opportunity to study the origin of self-organized
      criticality (SOC) in social systems. In contrast to physical systems in the
      laboratory, various human attributes of the actors play an essential role in the
      process along with the contents (cognitive, emotional) of the communicated
      artifacts. As a prototypical example, we consider the social endeavor of
      knowledge creation via Questions and Answers (Q&A). Using a large empirical data
      set from one of such Q&A sites and theoretical modeling, we reveal fundamental
      characteristics of SOC by investigating the temporal correlations at all scales
      and the role of cognitive contents to the avalanches of the knowledge-creation
      process. Our analysis shows that the universal social dynamics with power-law
      inhomogeneities of the actions and delay times provides the primary mechanism for
      self-tuning towards the critical state; it leads to the long-range correlations
      and the event clustering in response to the external driving by the arrival of
      new users. In addition, the involved cognitive contents (systematically annotated
      in the data and observed in the model) exert important constraints that identify
      unique classes of the knowledge-creation avalanches. Specifically, besides
      determining a fine structure of the developing knowledge networks, they affect
      the values of scaling exponents and the geometry of large avalanches and shape
      the multifractal spectrum. Furthermore, we find that the level of the activity of
      the communities that share the knowledge correlates with the fluctuations of the
      innovation rate, implying that the increase of innovation may serve as the active
      principle of self-organization. To identify relevant parameters and unravel the
      role of the network evolution underlying the process in the social system under
      consideration, we compare the social avalanches to the avalanche sequences
      occurring in the field-driven physical model of disordered solids, where the
      factors contributing to the collective dynamics are better understood.

PMID- 29346909
TI  - Random matrices and the New York City subway system.
AB  - We analyze subway arrival times in the New York City subway system. We find
      regimes where the gaps between trains are well modeled by (unitarily invariant)
      random matrix statistics and Poisson statistics. The departure from random matrix
      statistics is captured by the value of the Coulomb potential along the subway
      route. This departure becomes more pronounced as trains make more stops.

PMID- 29346910
TI  - Dynamics-dependent synchronization in on-chip coupled semiconductor lasers.
AB  - Synchronization properties of chaotic dynamics in two mutually coupled
      semiconductor lasers with optical feedback embedded in a photonic integrated
      circuit are investigated from the point of view of their dynamical content. A
      phenomenon in which the two lasers can show qualitatively different
      synchronization properties according to the frequency range of investigation and
      their nonlinear dynamics is identified and termed dynamics-dependent
      synchronization. In-phase synchronization is observed for original signals and
      antiphase synchronization is observed for low-pass filtered signals in the case
      where one of the lasers shows chaotic oscillations while the other laser exhibits
      low-frequency fluctuations dynamics. The experimental conditions causing the
      synchronization states to vary according to the considered frequency interval are
      studied and the key roles of asymmetric coupling strength and injection currents
      are clarified.

PMID- 29346911
TI  - Avalanche precursors in a frictional model.
AB  - We present a one-dimensional numerical model based on elastically coupled sliders
      on a frictional incline of variable tilt. This very simple approach makes it
      possible to study the precursors to the avalanche and to provide a
      rationalization of different features that have been observed in experiments. We
      provide a statistical description of the model leading to master equations
      describing the state of the system as a function of the angle of inclination. Our
      central results are the reproduction of large-scale regular events preceding the
      avalanche, on the one hand, and an analytical approach providing an internal
      threshold for the outbreak of rearrangements before the avalanche in the system,
      on the other hand.

PMID- 29346912
TI  - Wedge wetting by electrolyte solutions.
AB  - The wetting of a charged wedgelike wall by an electrolyte solution is
      investigated by means of classical density functional theory. As in other studies
      on wedge wetting, this geometry is considered as the most simple deviation from a
      planar substrate, and it serves as a first step toward more complex confinements
      of fluids. By focusing on fluids containing ions and surface charges, features of
      real systems are covered that are not accessible within the vast majority of
      previous theoretical studies concentrating on simple fluids in contact with
      uncharged wedges. In particular, the filling transition of charged wedges is
      necessarily of first order, because wetting transitions of charged substrates are
      of first order and the barrier in the effective interface potential persists
      below the wetting transition of a planar wall; hence, critical filling
      transitions are not expected to occur for ionic systems. The dependence of the
      critical opening angle on the surface charge, as well as the dependence of the
      filling height, of the wedge adsorption, and of the line tension on the opening
      angle and on the surface charge are analyzed in detail.

PMID- 29346913
TI  - Strained-graphene-based highly efficient quantum heat engine operating at maximum
      power.
AB  - A strained graphene monolayer is shown to operate as a highly efficient quantum
      heat engine delivering maximum power. The efficiency and power of the proposed
      device exceeds that of recent proposals. The reason for these excellent
      characteristics is that strain enables complete valley separation in
      transmittance through the device, implying that increasing strain leads to very
      high Seebeck coefficient as well as lower conductance. In addition, since time
      reversal symmetry is unbroken in our system, the proposed strained graphene
      quantum heat engine can also act as a high-performance refrigerator.

PMID- 29346914
TI  - Noise-induced torus bursting in the stochastic Hindmarsh-Rose neuron model.
AB  - We study the phenomenon of noise-induced torus bursting on the base of the three
      dimensional Hindmarsh-Rose neuron model forced by additive noise. We show that in
      the parametric zone close to the Neimark-Sacker bifurcation, where the
      deterministic system exhibits rapid tonic spiking oscillations, random
      disturbances can turn tonic spiking into bursting, which is characterized by the
      formation of a peculiar dynamical structure resembling that of a torus. This
      phenomenon is confirmed by the changes in dispersion of random trajectories as
      well as the power spectral density and interspike intervals statistics. In
      particular, we show that as noise increases, the system undergoes P and D
      bifurcations, transitioning from order to chaos. We ultimately characterize the
      transition from stochastic (tonic) spiking to bursting by stochastic sensitivity
      functions.

PMID- 29346915
TI  - Efficient method for estimating the number of communities in a network.
AB  - While there exist a wide range of effective methods for community detection in
      networks, most of them require one to know in advance how many communities one is
      looking for. Here we present a method for estimating the number of communities in
      a network using a combination of Bayesian inference with a novel prior and an
      efficient Monte Carlo sampling scheme. We test the method extensively on both
      real and computer-generated networks, showing that it performs accurately and
      consistently, even in cases where groups are widely varying in size or structure.

PMID- 29346916
TI  - Construction of and efficient sampling from the simplicial configuration model.
AB  - Simplicial complexes are now a popular alternative to networks when it comes to
      describing the structure of complex systems, primarily because they encode
      multinode interactions explicitly. With this new description comes the need for
      principled null models that allow for easy comparison with empirical data. We
      propose a natural candidate, the simplicial configuration model. The core of our
      contribution is an efficient and uniform Markov chain Monte Carlo sampler for
      this model. We demonstrate its usefulness in a short case study by investigating
      the topology of three real systems and their randomized counterparts (using their
      Betti numbers). For two out of three systems, the model allows us to reject the
      hypothesis that there is no organization beyond the local scale.

PMID- 29346917
TI  - Structural and dynamical characterization of water on the Au (100) and graphene
      surfaces: A molecular dynamics simulation approach.
AB  - The positioning, adsorption, and movement of water on substrates is dependent
      upon the chemical nature and arrangement of the atoms of the surface. Therefore
      the behavior of water molecules on a substrate is a reflection of properties of
      the surface. Based on this premise, graphene and gold substrates were chosen to
      study this subject from a molecular perspective. In this work, the structural and
      dynamical behaviors of a water nanodroplet on Au (100) and the graphene
      interfaces have been studied by molecular dynamics simulation. The results have
      shown how the structural and dynamical behaviors of water molecules at the
      interface reflect the characteristics of these surfaces. The results have
      demonstrated that residence time and hydrogen bonds' lifetime at the water-Au
      (100) interface are bigger than at the water-graphene interface. Energy contour
      map analysis indicates a more uniform surface energy on graphene than on the gold
      surface. The obtained results illustrate that water clusters on gold and graphene
      form tetramer and hexamer structures, respectively. Furthermore, the water
      molecules are more ordered on the gold surface than on graphene. The study of
      hydrogen bonds showed that the order, stability, and the number of hydrogen bonds
      is higher on the gold surface. The positioning pattern of water molecules is also
      similar to the arrangement of gold atoms while no regularity was observed on
      graphene. The study of dynamical behavior of water molecules revealed that the
      movement of water on gold is much less than on graphene which is in agreement
      with the strong water-gold interaction in comparison to the water-graphene
      interaction.

PMID- 29346918
TI  - Random walk to describe diffusion phenomena in three-dimensional discontinuous
      media: Step-balance and fictitious-velocity corrections.
AB  - In this paper, we show that diffusion phenomena in three-dimensional
      discontinuous media can be described as a random walk by two simple interface
      correction methods, namely step-balance and fictitious-velocity corrections,
      which are completely different in a physical picture but equivalent in that the
      continuity of the random walk at interfaces is considered. In both corrections,
      asymmetric interface permeability of a random walker, which comes from ensuring
      the continuity, causes apparent confinement of the walker in higher-diffusivity
      layers for benchmark tests on heat diffusion in two-phase multilayered systems.
      Effective thermal conductivities (walker diffusivities) computed from the
      trajectories are in excellent agreement with the series and parallel conduction
      formulas, indicating the equivalence of the two corrections and the importance of
      ensuring the continuity of a random walk at interfaces.

PMID- 29346919
TI  - Balancing building and maintenance costs in growing transport networks.
AB  - The costs associated to the length of links impose unavoidable constraints to the
      growth of natural and artificial transport networks. When future network
      developments cannot be predicted, the costs of building and maintaining
      connections cannot be minimized simultaneously, requiring competing optimization
      mechanisms. Here, we study a one-parameter nonequilibrium model driven by an
      optimization functional, defined as the convex combination of building cost and
      maintenance cost. By varying the coefficient of the combination, the model
      interpolates between global and local length minimization, i.e., between minimum
      spanning trees and a local version known as dynamical minimum spanning trees. We
      show that cost balance within this ensemble of dynamical networks is a sufficient
      ingredient for the emergence of tradeoffs between the network's total length and
      transport efficiency, and of optimal strategies of construction. At the
      transition between two qualitatively different regimes, the dynamics builds up
      power-law distributed waiting times between global rearrangements, indicating a
      point of nonoptimality. Finally, we use our model as a framework to analyze
      empirical ant trail networks, showing its relevance as a null model for cost
      constrained network formation.

PMID- 29346920
TI  - Conditional 1/f^{alpha} noise: From single molecules to macroscopic measurement.
AB  - We demonstrate that the measurement of 1/f^{alpha} noise at the single molecule
      or nano-object limit is remarkably distinct from the macroscopic measurement over
      a large sample. The single-particle measurements yield a conditional time
      dependent spectrum. However, the number of units fluctuating on the time scale of
      the experiment is increasing in such a way that the macroscopic measurements
      appear perfectly stationary. The single-particle power spectrum is a conditional
      spectrum, in the sense that we must make a distinction between idler and nonidler
      units on the time scale of the experiment. We demonstrate our results based on
      stochastic and deterministic models, in particular the well-known approach of
      superimposed Lorentzians, the blinking quantum dot model, and deterministic
      dynamics generated by a nonlinear mapping. Our results show that the 1/f^{alpha}
      spectrum is inherently nonstationary even if the macroscopic measurement
      completely obscures the underlying time dependence of the phenomena.

PMID- 29346921
TI  - Orthotropic hydraulic permeability of arrays of parallel cylinders.
AB  - Approximate analytical methods are presented to calculate the overall orthotropic
      hydraulic permeability of a flow with low Reynolds number, passing through a
      bundle of parallel circular cylinders. Two particular distributions are
      considered: (i) arrays with ordered rectangular lattices and (ii) irregular
      nonrandom distributions for which the unit cell cross sections are elliptical.
      The standard unit cell models, originally developed by Happel and Kuwabara for a
      random distribution of cylinders, are adapted to the case of nonrandom
      distributions. The drag force on a representative cylinder in a direction
      perpendicular to its axis is obtained based on the standard unit cell model: the
      actual unit cell of rectangular or elliptical cross section is replaced with an
      "equivalent" cylindrical unit cell of diameter equal to the maximum width of the
      actual unit cell. Using the obtained drag forces and referring back to the
      original geometry of the unit cell, closed-form approximate expressions for the
      overall permeabilities in the perpendicular directions are obtained. Numerical
      comparisons with more sophisticated approaches confirm the good efficiency of the
      presented approach, especially in the range of low solid volume fraction, i.e.,
      of high porosity. Previous studies have revealed that, for the parallel fluid
      flow, the variation of permeability with aspect ratio (or in general the lateral
      arrangement) of parallel cylinders is generally weak. These observations suggest
      that Happel's model for parallel permeability in a random distribution of
      cylinders could be a good approximation for parallel permeabilities in nonrandom
      distributions with the same volume fraction.

PMID- 29346922
TI  - Effects of viscous heating and wall-fluid interaction energy on rate-dependent
      slip behavior of simple fluids.
AB  - Molecular dynamics simulations are used to investigate the rate and temperature
      dependence of the slip length in thin liquid films confined by smooth, thermal
      substrates. In our setup, the heat generated in a force-driven flow is removed by
      the thermostat applied on several wall layers away from liquid-solid interfaces.
      We found that for both high and low wall-fluid interaction (WFI) energies, the
      temperature of the fluid phase rises significantly as the shear rate increases.
      Surprisingly, with increasing shear rate, the slip length approaches a constant
      value from above for high WFI energies and from below for low WFI energies. The
      two distinct trends of the rate-dependent slip length are rationalized by
      examining S(G_{1}), the height of the main peak of the in-plane structure factor
      of the first fluid layer (FFL) together with D_{WF}, which is the average
      distance between the wall and FFL. The results of numerical simulations
      demonstrate that reduced values of the structure factor, S(G_{1}), correlate with
      the enhanced slip, while smaller distances D_{WF} indicate that fluid atoms
      penetrate deeper into the surface potential leading to larger friction and
      smaller slip. Interestingly, at the lowest WFI energy, the combined effect of the
      increase of S(G_{1}) and decrease of D_{WF} with increasing shear rate results in
      a dramatic reduction of the slip length.

PMID- 29346923
TI  - Unifying different interpretations of the nonlinear response in glass-forming
      liquids.
AB  - This work aims at reconsidering several interpretations coexisting in the recent
      literature concerning nonlinear susceptibilities in supercooled liquids. We
      present experimental results on glycerol and propylene carbonate, showing that
      the three independent cubic susceptibilities have very similar frequency and
      temperature dependences, for both their amplitudes and phases. This strongly
      suggests a unique physical mechanism responsible for the growth of these
      nonlinear susceptibilities. We show that the framework proposed by two of us [J.
      P. Bouchaud and G. Biroli, Phys. Rev. B 72, 064204 (2005)PRBMDO1098
      012110.1103/PhysRevB.72.064204], where the growth of nonlinear susceptibilities
      is intimately related to the growth of glassy domains, accounts for all the
      salient experimental features. We then review several complementary and/or
      alternative models and show that the notion of cooperatively rearranging glassy
      domains is a key (implicit or explicit) ingredient to all of them. This paves the
      way for future experiments, which should deepen our understanding of glasses.

PMID- 29346924
TI  - Multiclustered chimeras in large semiconductor laser arrays with nonlocal
      interactions.
AB  - The dynamics of a large array of coupled semiconductor lasers is studied
      numerically for a nonlocal coupling scheme. Our focus is on chimera states, a
      self-organized spatiotemporal pattern of coexisting coherence and incoherence. In
      laser systems, such states have been previously found for global and nearest
      neighbor coupling, mainly in small networks. The technological advantage of large
      arrays has motivated us to study a system of 200 nonlocally coupled lasers with
      respect to the emerging collective dynamics. Moreover, the nonlocal nature of the
      coupling allows us to obtain robust chimera states with multiple (in)coherent
      domains. The crucial parameters are the coupling strength, the coupling phase and
      the range of the nonlocal interaction. We find that multiclustered chimera states
      exist in a wide region of the parameter space and we provide quantitative
      characterization for the obtained spatiotemporal patterns. By proposing two
      different experimental setups for the realization of the nonlocal coupling
      scheme, we are confident that our results can be confirmed in the laboratory.

PMID- 29346925
TI  - Cluster sizes in a classical Lennard-Jones chain.
AB  - The definitions of breaks and clusters in a one-dimensional chain in equilibrium
      are discussed. Analytical expressions are obtained for the expected cluster
      length, <K>, as a function of temperature and pressure in a one-dimensional
      Lennard-Jones chain. These expressions are compared with results from molecular
      dynamics simulations. It is found that <K> increases exponentially with
      beta=1/k_{B}T and with pressure, P in agreement with previous results in the
      literature. A method is illustrated for using <K>(beta,P) to generate a "phase
      diagram" for the Lennard-Jones chain. Some implications for the study of heat
      transport in Lennard-Jones chains are discussed.

PMID- 29346926
TI  - Convection induced by thermal gradients on thin reaction fronts.
AB  - We present a thin front model for the propagation of chemical reaction fronts in
      liquids inside a Hele-Shaw cell or porous media. In this model we take into
      account density gradients due to thermal and compositional changes across a thin
      interface. The front separating reacted from unreacted fluids evolves following
      an eikonal relation between the normal speed and the curvature. We carry out a
      linear stability analysis of convectionless flat fronts confined in a two
      dimensional rectangular domain. We find that all fronts are stable to
      perturbations of short wavelength, but they become unstable for some wavelengths
      depending on the values of compositional and thermal gradients. If the effects of
      these gradients oppose each other, we observe a range of wavelengths that make
      the flat front unstable. Numerical solutions of the nonlinear model show curved
      fronts of steady shape with convection propagating faster than flat fronts.
      Exothermic fronts increase the temperature of the fluid as they propagate through
      the domain. This increment in temperature decreases with increasing speed.

PMID- 29346927
TI  - Topological inversions in coalescing granular media control fluid-flow regimes.
AB  - Sintering-or coalescence-of viscous droplets is an essential process in many
      natural and industrial scenarios. Current physical models of the dynamics of
      sintering are limited by the lack of an explicit account of the evolution of
      microstructural geometry. Here, we use high-speed time-resolved x-ray tomography
      to image the evolving geometry of a sintering system of viscous droplets, and use
      lattice Boltzmann simulations of creeping fluid flow through the reconstructed
      pore space to determine its permeability. We identify and characterize a
      topological inversion, from spherical droplets in a continuous interstitial gas,
      to isolated bubbles in a continuous liquid. We find that the topological
      inversion is associated with a transition in permeability-porosity behavior, from
      Stokes permeability at high porosity, to percolation theory at low porosity. We
      use these findings to construct a unified physical description that reconciles
      previously incompatible models for the evolution of porosity and permeability
      during sintering.

PMID- 29346928
TI  - Signatures of classical structures in the leading eigenstates of quantum
      dissipative systems.
AB  - By analyzing a paradigmatic example of the theory of dissipative systems-the
      classical and quantum dissipative standard map-we are able to explain the main
      features of the decay to the quantum equilibrium state. The classical isoperiodic
      stable structures typically present in the parameter space of these kinds of
      systems play a fundamental role. In fact, we have found that the period of stable
      structures that are near in this space determines the phase of the leading
      eigenstates of the corresponding quantum superoperator. Moreover, the
      eigenvectors show a strong localization on the corresponding periodic orbits
      (limit cycles). We show that this sort of scarring phenomenon (an established
      property of Hamiltonian and projectively open systems) is present in the
      dissipative case and it is of extreme simplicity.

PMID- 29346929
TI  - Numerical estimation of structure constants in the three-dimensional Ising
      conformal field theory through Markov chain uv sampler.
AB  - Herdeiro and Doyon [Phys. Rev. E 94, 043322 (2016)2470
      004510.1103/PhysRevE.94.043322] introduced a numerical recipe, dubbed uv sampler,
      offering precise estimations of the conformal field theory (CFT) data of the
      planar two-dimensional (2D) critical Ising model. It made use of scale invariance
      emerging at the critical point in order to sample finite sublattice marginals of
      the infinite plane Gibbs measure of the model by producing holographic boundary
      distributions. The main ingredient of the Markov chain Monte Carlo sampler is the
      invariance under dilation. This paper presents a generalization to higher
      dimensions with the critical 3D Ising model. This leads to numerical estimations
      of a subset of the CFT data-scaling weights and structure constants-through
      fitting of measured correlation functions. The results are shown to agree with
      the recent most precise estimations from numerical bootstrap methods [Kos,
      Poland, Simmons-Duffin, and Vichi, J. High Energy Phys. 08 (2016)
      03610.1007/JHEP08(2016)036].

PMID- 29346930
TI  - Proxy-equation paradigm: A strategy for massively parallel asynchronous
      computations.
AB  - Massively parallel simulations of transport equation systems call for a paradigm
      change in algorithm development to achieve efficient scalability. Traditional
      approaches require time synchronization of processing elements (PEs), which
      severely restricts scalability. Relaxing synchronization requirement introduces
      error and slows down convergence. In this paper, we propose and develop a novel
      "proxy equation" concept for a general transport equation that (i) tolerates
      asynchrony with minimal added error, (ii) preserves convergence order and thus,
      (iii) expected to scale efficiently on massively parallel machines. The central
      idea is to modify a priori the transport equation at the PE boundaries to offset
      asynchrony errors. Proof-of-concept computations are performed using a one
      dimensional advection (convection) diffusion equation. The results demonstrate
      the promise and advantages of the present strategy.

PMID- 29346931
TI  - Equation-based model for the stock market.
AB  - We propose a stock market model which is investigated in the forms of difference
      and differential equations whose variables correspond to the demand or supply of
      each agent and to the price. In the model, agents are driven by the behavior of
      their trust contact network as well by fundamental analysis. By means of the
      deterministic version of the model, the connection between such drive mechanisms
      and the price is analyzed: imitation behavior promotes market instability,
      finitude of resources is associated to stock index stability, and high
      sensitivity to the fair price provokes price oscillations. Long-range
      correlations in the price temporal series and heavy-tailed distribution of
      returns are observed for the version of the model which considers different
      proposals for stochasticity of microeconomic and macroeconomic origins.

PMID- 29346932
TI  - Gap-junction coupling and ATP-sensitive potassium channels in human beta-cell
      clusters: Effects on emergent dynamics.
AB  - The importance of gap-junction coupling between beta cells in pancreatic islets
      is well established in mouse. Such ultrastructural connections synchronize
      cellular activity, confine biological heterogeneity, and enhance insulin
      pulsatility. Dysfunction of coupling has been associated with diabetes and
      altered beta-cell function. However, the role of gap junctions between human beta
      cells is still largely unexplored. By using patch-clamp recordings of beta cells
      from human donors, we previously estimated electrical properties of these
      channels by mathematical modeling of pairs of human beta cells. In this work we
      revise our estimate by modeling triplet configurations and larger heterogeneous
      clusters. We find that a coupling conductance in the range 0.005-0.020 nS/pF can
      reproduce experiments in almost all the simulated arrangements. We finally
      explore the consequence of gap-junction coupling of this magnitude between beta
      cells with mutant variants of the ATP-sensitive potassium channels involved in
      some metabolic disorders and diabetic conditions, translating studies performed
      on rodents to the human case. Our results are finally discussed from the
      perspective of therapeutic strategies. In summary, modeling of more realistic
      clusters with more than two beta cells slightly lowers our previous estimate of
      gap-junction conductance and gives rise to patterns that more closely resemble
      experimental traces.

PMID- 29346933
TI  - Internal temperature of quantum chaotic systems at the nanoscale.
AB  - The extent to which a temperature can be appropriately assigned to a small
      quantum system, as an internal property but not as a property of any large
      environment, is still an open problem. In this paper, a method is proposed for
      solving this problem, by which a studied small system is coupled to a two-level
      system as a probe, the latter of which can be measured by measurement devices. A
      main difficulty in the determination of possible temperature of the studied
      system comes from the back-action of the probe-system coupling to the system. For
      small quantum chaotic systems, we show that a temperature can be determined, the
      value of which is sensitive to neither the form, location, and strength of the
      probe-system coupling, nor the Hamiltonian and initial state of the probe. The
      temperature thus obtained turns out to have the form of Boltzmann temperature.

PMID- 29346934
TI  - Kardar-Parisi-Zhang modes in d-dimensional directed polymers.
AB  - We define a stochastic lattice model for a fluctuating directed polymer in d>=2
      dimensions. This model can be alternatively interpreted as a fluctuating random
      path in two dimensions, or a one-dimensional asymmetric simple exclusion process
      with d-1 conserved species of particles. The deterministic large dynamics of the
      directed polymer are shown to be given by a system of coupled Kardar-Parisi-Zhang
      (KPZ) equations and diffusion equations. Using nonlinear fluctuating
      hydrodynamics and mode coupling theory we argue that stationary fluctuations in
      any dimension d can only be of KPZ type or diffusive. The modes are pure in the
      sense that there are only subleading couplings to other modes, thus excluding the
      occurrence of modified KPZ-fluctuations or Levy-type fluctuations, which are
      common for more than one conservation law. The mode-coupling matrices are shown
      to satisfy the so-called trilinear condition.

PMID- 29346935
TI  - Chase-and-run dynamics in cell motility and the molecular rupture of interacting
      active elastic dimers.
AB  - Cell migration in morphogenesis and cancer metastasis typically involves
      interplay between different cell types. We construct and study a minimal, one
      dimensional model composed of two different motile cells with each cell
      represented as an active elastic dimer. The interaction between the two cells via
      cadherins is modeled as a spring that can rupture beyond a threshold force as it
      undergoes dynamic loading from the interacting motile cells. We obtain a phase
      diagram consisting of chase-and-run dynamics and clumping dynamics as a function
      of the stiffness of the interaction spring and the threshold force and,
      therefore, posit that active rupture, or rupture via active forces, is a
      mechanosensitive means to regulate dynamics between cells. Since the parameters
      in the model differentiate between N- and E-cadherins, we make predictions for
      the interactions between a placodelike cell and a neural crestlike cell in a
      microchannel as well as discuss how our results inform chase-and-run dynamics
      found in a group of placode cells interacting with a group of neural crest cells.
      In particular, an argument was made in the latter case that the feedback between
      cadherins and cell-substrate interaction via integrins was necessary to obtain
      the chase-and-run behavior. Based on our two-cell results, we argue that this
      feedback accentuates, but is not necessary for, the chase-and-run behavior.

PMID- 29346936
TI  - Accessibility and delay in random temporal networks.
AB  - In a wide range of complex networks, the links between the nodes are temporal and
      may sporadically appear and disappear. This temporality is fundamental to
      analyzing the formation of paths within such networks. Moreover, the presence of
      the links between the nodes is a random process induced by nature in many real
      world networks. In this paper, we study random temporal networks at a microscopic
      level and formulate the probability of accessibility from a node i to a node j
      after a certain number of discrete time units T. While solving the original
      problem is computationally intractable, we provide an upper and two lower bounds
      on this probability for a very general case with arbitrary time-varying
      probabilities of the links' existence. Moreover, for a special case where the
      links have identical probabilities across the network at each time slot, we
      obtain the exact probability of accessibility between any two nodes. Finally, we
      discuss scenarios where the information regarding the presence and absence of
      links is initially available in the form of time duration (of presence or absence
      intervals) continuous probability distributions rather than discrete
      probabilities over time slots. We provide a method for transforming such
      distributions to discrete probabilities, which enables us to apply the given
      bounds in this paper to a broader range of problem settings.

PMID- 29346937
TI  - Uhlenbeck-Ford model: Phase diagram and corresponding-states analysis.
AB  - Using molecular dynamics simulations and nonequilibrium thermodynamic-integration
      techniques we compute the Helmholtz free energies of the body-centered-cubic
      (bcc), face-centered-cubic (fcc), hexagonal close-packed, and fluid phases of the
      Uhlenbeck-Ford model (UFM) and use the results to construct its phase diagram.
      The pair interaction associated with the UFM is characterized by an ultrasoft,
      purely repulsive pair potential that diverges logarithmically at the origin. We
      find that the bcc and fcc are the only thermodynamically stable crystalline
      phases in the phase diagram. Furthermore, we report the existence of two
      reentrant transition sequences as a function of the number density, one featuring
      a fluid-bcc-fluid succession and another displaying a bcc-fcc-bcc sequence near
      the triple point. We find strong resemblances to the phase behavior of other
      soft, purely repulsive systems such as the Gaussian-core model (GCM), inverse
      power-law, and Yukawa potentials. In particular, we find that the fcc-bcc-fluid
      triple point and the phase boundaries in its vicinity are in good agreement with
      the prediction supplied by a recently proposed corresponding-states principle [J.
      Chem. Phys. 134, 241101 (2011)JCPSA60021-960610.1063/1.3605659; Europhys. Lett.
      100, 66004 (2012)EULEEJ0295-507510.1209/0295-5075/100/66004]. The particularly
      strong resemblance between the behavior of the UFM and GCM models are also
      discussed.

PMID- 29346938
TI  - Equilibrium position of a rigid sphere in a turbulent jet: A problem of elastic
      reconfiguration.
AB  - The position of floating spheres trapped within an immersed turbulent water jet
      is investigated. Using the self-similarity properties of the jet velocity
      profile, the equilibrium problem is formulated in a rescaled space where the
      sphere is static and deformable. This approach is found to be related to a
      problem of elastic reconfiguration where elasticity arises here from the geometry
      of the flow instead of an actual deformation of a body.

PMID- 29346939
TI  - Promoting information diffusion through interlayer recovery processes in
      multiplex networks.
AB  - For information diffusion in multiplex networks, the effect of interlayer
      contagion on spreading dynamics has been explored in different settings.
      Nevertheless, the impact of interlayer recovery processes, i.e., the transition
      of nodes to stiflers in all layers after they become stiflers in any layer, still
      remains unclear. In this paper, we propose a modified ignorant-spreader-stifler
      model of rumor spreading equipped with an interlayer recovery mechanism. We find
      that the information diffusion can be effectively promoted for a range of
      interlayer recovery rates. By combining the mean-field approximation and the
      Markov chain approach, we derive the evolution equations of the diffusion process
      in two-layer homogeneous multiplex networks. The optimal interlayer recovery rate
      that achieves the maximal enhancement can be calculated by solving the equations
      numerically. In addition, we find that the promoting effect on a certain layer
      can be strengthened if information spreads more extensively within the
      counterpart layer. When applying the model to two-layer scale-free multiplex
      networks, with or without degree correlation, similar promoting effect is also
      observed in simulations. Our work indicates that the interlayer recovery process
      is beneficial to information diffusion in multiplex networks, which may have
      implications for designing efficient spreading strategies.

PMID- 29346940
TI  - Advective superdiffusion in superhydrophobic microchannels.
AB  - We consider pressure-driven flows in wide microchannels, and discuss how a
      transverse shear, generated by misaligned superhydrophobic walls, impacts cross
      sectional spreading of Brownian particles. We show that such a transverse shear
      can induce an advective superdiffusion, which strongly enhances dispersion of
      particles compared to a normal diffusion, and that maximal cross-sectional
      spreading corresponds to a crossover between its subballistic and superballistic
      regimes. This allows us to argue that an advective superdiffusion can be used for
      boosting dispersion of particles at smaller Peclet numbers compared to known
      concepts of passive microfluidic mixing. This implies that our superdiffusion
      scenario allows one efficient mixing of much smaller particles or using much
      thinner microchannels than methods, which are currently being exploited.

PMID- 29346941
TI  - Phase transition in the singularity spectrum of an intermingled basin.
AB  - A two-dimensional piecewise linear mapping is introduced as a solvable model to
      characterize the multifractal structure of an intermingled basin. To this end, we
      make use of the multifractal formalism and introduce a partition function. The
      singularity spectrum, which characterizes local scaling property of the
      intermingled basin, is then determined. We have found that if the system is not
      symmetric, the singularity spectrum of either basin shows a phase transition,
      corresponding to the existence of two phases the orbits experience in the system,
      i.e., local one governed by the chaotic motions on the chaotic attractor, and the
      other global one reflecting nonhyperbolic motions characteristic of the
      intermingled basin.

PMID- 29346942
TI  - Transitions in optimal adaptive strategies for populations in fluctuating
      environments.
AB  - Biological populations are subject to fluctuating environmental conditions.
      Different adaptive strategies can allow them to cope with these fluctuations:
      specialization to one particular environmental condition, adoption of a
      generalist phenotype that compromises between conditions, or population-wise
      diversification (bet hedging). Which strategy provides the largest selective
      advantage in the long run depends on the range of accessible phenotypes and the
      statistics of the environmental fluctuations. Here, we analyze this problem in a
      simple mathematical model of population growth. First, we review and extend a
      graphical method to identify the nature of the optimal strategy when the
      environmental fluctuations are uncorrelated. Temporal correlations in
      environmental fluctuations open up new strategies that rely on memory but are
      mathematically challenging to study: We present analytical results to address
      this challenge. We illustrate our general approach by analyzing optimal adaptive
      strategies in the presence of trade-offs that constrain the range of accessible
      phenotypes. Our results extend several previous studies and have applications to
      a variety of biological phenomena, from antibiotic resistance in bacteria to
      immune responses in vertebrates.

PMID- 29346943
TI  - Whitham modulation theory for the two-dimensional Benjamin-Ono equation.
AB  - Whitham modulation theory for the two-dimensional Benjamin-Ono (2DBO) equation is
      presented. A system of five quasilinear first-order partial differential
      equations is derived. The system describes modulations of the traveling wave
      solutions of the 2DBO equation. These equations are transformed to a singularity
      free hydrodynamic-like system referred to here as the 2DBO-Whitham system. Exact
      reductions of this system are discussed, the formulation of initial value
      problems is considered, and the system is used to study the transverse stability
      of traveling wave solutions of the 2DBO equation.

PMID- 29346944
TI  - Phase transition and power-law coarsening in an Ising-doped voter model.
AB  - We examine an opinion formation model, which is a mixture of Voter and Ising
      agents. Numerical simulations show that even a very small fraction (~1%) of the
      Ising agents drastically changes the behavior of the Voter model. The Voter
      agents act as a medium, which correlates sparsely dispersed Ising agents, and the
      resulting ferromagnetic ordering persists up to a certain temperature. Upon
      addition of the Ising agents, a logarithmically slow coarsening of the Voter
      model (d=2), or its active steady state (d=3), change into an Ising-type power
      law coarsening.

PMID- 29346945
TI  - Nonmonotonic dependence of polymer-glass mechanical response on chain bending
      stiffness.
AB  - We investigate the mechanical properties of amorphous polymers by means of coarse
      grained simulations and nonaffine lattice dynamics theory. A small increase of
      polymer chain bending stiffness leads first to softening of the material, while
      hardening happens only upon further strengthening of the backbones. This
      nonmonotonic variation of the storage modulus G^{'} with bending stiffness is
      caused by a competition between additional resistance to deformation offered by
      stiffer backbones and decreased density of the material due to a necessary
      decrease in monomer-monomer coordination. This counterintuitive finding suggests
      that the strength of polymer glasses may in some circumstances be enhanced by
      softening the bending of constituent chains.

PMID- 29346946
TI  - Flow and clog in a silo with oscillating exit.
AB  - When grains flow out of a silo, flow rate W increases with exit size D. If D is
      too small, an arch may form and the flow may be blocked at the exit. To recover
      from clogging, the arch has to be destroyed. Here we construct a two-dimensional
      silo with movable exit and study the effects of exit oscillation (with amplitude
      A and frequency f) on flow rate, clogging, and unclogging of grains through the
      exit. We find that, if exit oscillates, W remains finite even when D (measured in
      unit of grain diameter) is only slightly larger than one. Surprisingly, while W
      increases with oscillation strength Gamma=4pi^{2}Af^{2} as expected at small D, W
      decreases with Gamma when D>=5 due to induced random motion of the grains at the
      exit. When D is small and oscillation speed v=2piAf is slow, temporary clogging
      events cause the grains to flow intermittently. In this regime, W depends only on
      v-a feature consistent to a simple arch breaking mechanism, and the phase
      boundary of intermittent flow in the D-v plane is consistent to either a power
      law: D?v^{-7} or an exponential form: D?e^{-D/0.55}. Furthermore, the flow time
      statistic is Poissonian whereas the recovery time statistic follows a power-law
      distribution.

PMID- 29346947
TI  - Bragg solitons in systems with separated nonuniform Bragg grating and
      nonlinearity.
AB  - The existence and stability of quiescent Bragg grating solitons are
      systematically investigated in a dual-core fiber, where one of the cores is
      uniform and has Kerr nonlinearity while the other one is linear and incorporates
      a Bragg grating with dispersive reflectivity. Three spectral gaps are identified
      in the system, in which both lower and upper band gaps overlap with one branch of
      the continuous spectrum; therefore, these are not genuine band gaps. However, the
      central band gap is a genuine band gap. Soliton solutions are found in the lower
      and upper gaps only. It is found that in certain parameter ranges, the solitons
      develop side lobes. To analyze the side lobes, we have derived exact analytical
      expressions for the tails of solitons that are in excellent agreement with the
      numerical solutions. We have analyzed the stability of solitons in the system by
      means of systematic numerical simulations. We have found vast stable regions in
      the upper and lower gaps. The effect and interplay of dispersive reflectivity,
      the group velocity difference, and the grating-induced coupling on the stability
      of solitons are investigated. A key finding is that a stronger grating-induced
      coupling coefficient counteracts the stabilization effect of dispersive
      reflectivity.

PMID- 29346948
TI  - Regularized fractional Ornstein-Uhlenbeck processes and their relevance to the
      modeling of fluid turbulence.
AB  - Motivated by the modeling of the temporal structure of the velocity field in a
      highly turbulent flow, we propose and study a linear stochastic differential
      equation that involves the ingredients of an Ornstein-Uhlenbeck process,
      supplemented by a fractional Gaussian noise, of parameter H, regularized over a
      (small) time scale epsilon>0. A peculiar correlation between these two plays a
      key role in the establishment of the statistical properties of its solution. We
      show that this solution reaches a stationary regime, which marginals, including
      variance and increment variance, remain bounded when epsilon->0. In particular,
      in this limit, for any H?]0,1[, we show that the increment variance behaves at
      small scales as the one of a fractional Brownian motion of same parameter H. From
      the theoretical side, this approach appears especially well suited to deal with
      the (very) rough case H<1/2, including the boundary value H=0, and to design
      simple and efficient numerical simulations.

PMID- 29346949
TI  - Hyperuniformity disorder length spectroscopy for extended particles.
AB  - The concept of a hyperuniformity disorder length h was recently introduced for
      analyzing volume fraction fluctuations for a set of measuring windows [Chieco et
      al., Phys. Rev. E 96, 032909 (2017).PLEEE81539-375510.1103/PhysRevE.96.032909].
      This length permits a direct connection to the nature of disorder in the spatial
      configuration of the particles and provides a way to diagnose the degree of
      hyperuniformity in terms of the scaling of h and its value in comparison with
      established bounds. Here, this approach is generalized for extended particles,
      which are larger than the image resolution and can lie partially inside and
      partially outside the measuring windows. The starting point is an expression for
      the relative volume fraction variance in terms of four distinct volumes: that of
      the particle, the measuring window, the mean-squared overlap between particle and
      region, and the region over which particles have nonzero overlap with the
      measuring window. After establishing limiting behaviors for the relative
      variance, computational methods are developed for both continuum and pixelated
      particles. Exact results are presented for particles of special shape and for
      measuring windows of special shape, for which the equations are tractable.
      Comparison is made for other particle shapes, using simulated Poisson patterns.
      And the effects of polydispersity and image errors are discussed. For small
      measuring windows, both particle shape and spatial arrangement affect the form of
      the variance. For large regions, the variance scaling depends only on arrangement
      but particle shape sets the numerical proportionality. The combined understanding
      permit the measured variance to be translated to the spectrum of hyperuniformity
      lengths versus region size, as the quantifier of spatial arrangement. This
      program is demonstrated for a system of nonoverlapping particles at a series of
      increasing packing fractions as well as for an Einstein pattern of particles with
      several different extended shapes.

PMID- 29346950
TI  - Generalized Archimedes' principle in active fluids.
AB  - We show how a gradient in the motility properties of noninteracting pointlike
      active particles can cause a pressure gradient that pushes a large inert object.
      We calculate the force on an object inside a system of active particles with
      position-dependent motion parameters, in one and two dimensions, and show that a
      modified Archimedes' principle is satisfied. We characterize the system, both in
      terms of the model parameters and in terms of experimentally measurable
      quantities: the spatial profiles of the density, velocity and pressure. This
      theoretical analysis is motivated by recent experiments, which showed that the
      nucleus of a mouse oocyte (immature egg cell) moves from the cortex to the center
      due to a gradient of activity of vesicles propelled by molecular motors; it more
      generally applies to artificial systems of controlled localized activity.

PMID- 29346951
TI  - Universal exponent for transport in mixed Hamiltonian dynamics.
AB  - We compute universal distributions for the transition probabilities of a Markov
      model for transport in the mixed phase space of area-preserving maps and verify
      that the survival probability distribution for trajectories near an infinite
      island-around-island hierarchy exhibits, on average, a power-law decay with
      exponent gamma=1.57. This exponent agrees with that found from simulations of the
      Henon and Chirikov-Taylor maps. This provides evidence that the Meiss-Ott Markov
      tree model describes the transport for mixed systems.

PMID- 29346952
TI  - Fluctuations in an established transmission in the presence of a complex
      environment.
AB  - In various situations where wave transport is preeminent, like in wireless
      communication, a strong established transmission is present in a complex
      scattering environment. We develop a nonperturbative approach to describe
      emerging fluctuations which combines a transmitting channel and a chaotic
      background in a unified effective Hamiltonian. Modeling such a background by
      random matrix theory, we derive exact results for both transmission and
      reflection distributions at arbitrary absorption that is typically present in
      real systems. Remarkably, in such a complex scattering situation, the transport
      is governed by only two parameters: an absorption rate and the ratio of the so
      called spreading width to the natural width of the transmission line. In
      particular, we find that the established transmission disappears sharply when
      this ratio exceeds unity. The approach exemplifies the role of the chaotic
      background in dephasing the deterministic scattering.

PMID- 29346953
TI  - Quantum statistical effects in the mass transport of interstitial solutes in a
      crystalline solid.
AB  - The impact of quantum statistics on the many-body dynamics of a crystalline solid
      at finite temperatures containing an interstitial solute atom (ISA) is
      investigated. The Mori-Zwanzig theory allows the many-body dynamics of the
      crystal to be formulated and solved analytically within a pseudo-one-particle
      approach using the Langevin equation with a quantum fluctuation-dissipation
      relation (FDR) based on the Debye model. At the same time, the many-body dynamics
      is also directly solved numerically via the molecular dynamics approach with a
      Langevin heat bath based on the quantum FDR. Both the analytical and numerical
      results consistently show that below the Debye temperature of the host lattice,
      quantum statistics significantly impacts the ISA transport properties, resulting
      in major departures from both the Arrhenius law of diffusion and the Einstein
      Smoluchowski relation between the mobility and diffusivity. Indeed, we found that
      below one-third of the Debye temperature, effects of vibrations on the quantum
      mobility and diffusivity are both orders-of-magnitude larger and practically
      temperature independent. We have shown that both effects have their physical
      origin in the athermal lattice vibrations derived from the phonon ground state.
      The foregoing theory is tested in quantum molecular dynamics calculation of
      mobility and diffusivity of interstitial helium in bcc W. In this case, the
      Arrhenius law is only valid in a narrow range between ~300 and ~700 K. The
      diffusivity becomes temperature independent on the low-temperature side while
      increasing linearly with temperature on the high-temperature side.

PMID- 29346954
TI  - Dynamical pattern selection of growing cellular mosaic in fish retina.
AB  - A Markovian lattice model for photoreceptor cells is introduced to describe the
      growth of mosaic patterns on fish retina. The radial stripe pattern observed in
      wild-type zebrafish is shown to be selected naturally during retina growth,
      against the geometrically equivalent circular stripe pattern. The mechanism of
      such dynamical pattern selection is clarified on the basis of both numerical
      simulations and theoretical analyses, which find that the successive emergence of
      local defects plays a critical role in the realization of the wild-type pattern.

PMID- 29346955
TI  - Ehrenfest urn model with interaction.
AB  - We studied the Ehrenfest urn model in which particles in the same urn interact
      with each other. Depending on the nature of interaction, the system undergoes a
      first- or second-order phase transition. The relaxation time to the equilibrium
      state, the Poincare cycles of the equilibrium state and the most far-from
      equilibrium state, and the duration time of the states during first-order phase
      transition are calculated. It was shown that the scaling behavior the Poincare
      cycles could serve as an indication to the nature of phase transition, and the
      behavior of the ratio of duration time of the states could be strong evidence of
      the metastability during first-order phase transition.

PMID- 29346956
TI  - Pseudoinverse of the Laplacian and best spreader node in a network.
AB  - Determining a set of "important" nodes in a network constitutes a basic endeavor
      in network science. Inspired by electrical flows in a resistor network, we
      propose the best conducting node j in a graph G as the minimizer of the diagonal
      element Q_{jj}^{?} of the pseudoinverse matrix Q^{?} of the weighted Laplacian
      matrix of the graph G. We propose a new graph metric that complements the
      effective graph resistance R_{G} and that specifies the heterogeneity of the
      nodal spreading capacity in a graph. Various formulas and bounds for the diagonal
      element Q_{jj}^{?} are presented. Finally, we compute the pseudoinverse matrix of
      the Laplacian of star, path, and cycle graphs and derive an expansion and lower
      bound of the effective graph resistance R_{G} based on the complement of the
      graph G.

PMID- 29346957
TI  - Double transition in a model of oscillating percolation.
AB  - Two distinct transition points have been observed in a problem of lattice
      percolation studied using a system of pulsating disks. Sites on a regular lattice
      are occupied by circular disks whose radii vary sinusoidally within [0,R_{0}]
      starting from a random distribution of phase angles. A lattice bond is said to be
      connected when its two end disks overlap with each other. Depending on the
      difference of the phase angles of these disks, a bond may be termed as dead or
      live. While a dead bond can never be connected, a live bond is connected at least
      once in a complete time period. Two different time scales can be associated with
      such a system, leading to two transition points. Namely, a percolation transition
      occurs at R_{0c}=0.908(5) when a spanning cluster of connected bonds emerges in
      the system. Here, information propagates across the system instantly, i.e., with
      infinite speed. Secondly, there exists another transition point
      R_{0}^{*}=0.5907(3) where the giant cluster of live bonds spans the lattice. In
      this case the information takes finite time to propagate across the system
      through the dynamical evolution of finite-size clusters. This passage time
      diverges as R_{0}->R_{0}^{*} from above. Both the transitions exhibit the
      critical behavior of ordinary percolation transition. The entire scenario is
      robust with respect to the distribution of frequencies of the individual disks.
      This study may be relevant in the context of wireless sensor networks.

PMID- 29346958
TI  - Electroclinic effect in chiral smectic-A liquid crystal elastomers.
AB  - Chiral smectic-A liquid crystal elastomers are rubbery materials composed of a
      lamellar arrangement of liquid crystalline mesogens. It has been shown
      experimentally that these materials shear when subjected to an electric field due
      to the electrically induced tilt of the director. Experiments have also shown
      that shearing a chiral smectic-A elastomer gives rise to a polarization. Roughly,
      the shear force tilts the directors which, in turn, induce electric dipoles. This
      paper builds on previous works and models the electromechanical response of
      smectic-A elastomers using free energy contributions that are associated with the
      lamellar structure, the relative tilt between the director and the layer normal,
      and the coupling between the director and the electric field. To illustrate the
      merit of the proposed model, two cases are considered-a deformation induced
      polarization and an electrically induced deformation. The predictions according
      to these two models qualitatively agree with experimental findings. Finally, a
      cylinder composed of helical smectic layers is also considered. It is shown that
      the electromechanical response varies as a function of the helix angle.

PMID- 29346959
TI  - Complex free-energy landscapes in biaxial nematic liquid crystals and the role of
      repulsive interactions: A Wang-Landau study.
AB  - General quadratic Hamiltonian models, describing the interaction between liquid
      crystal molecules (typically with D_{2h} symmetry), take into account couplings
      between their uniaxial and biaxial tensors. While the attractive contributions
      arising from interactions between similar tensors of the participating molecules
      provide for eventual condensation of the respective orders at suitably low
      temperatures, the role of cross coupling between unlike tensors is not fully
      appreciated. Our recent study with an advanced Monte Carlo technique (entropic
      sampling) showed clearly the increasing relevance of this cross term in
      determining the phase diagram (contravening in some regions of model parameter
      space), the predictions of mean-field theory, and standard Monte Carlo simulation
      results. In this context, we investigated the phase diagrams and the nature of
      the phases therein on two trajectories in the parameter space: one is a line in
      the interior region of biaxial stability believed to be representative of the
      real systems, and the second is the extensively investigated parabolic path
      resulting from the London dispersion approximation. In both cases, we find the
      destabilizing effect of increased cross-coupling interactions, which invariably
      result in the formation of local biaxial organizations inhomogeneously
      distributed. This manifests as a small, but unmistakable, contribution of biaxial
      order in the uniaxial phase. The free-energy profiles computed in the present
      study as a function of the two dominant order parameters indicate complex
      landscapes. On the one hand, these profiles account for the unusual thermal
      behavior of the biaxial order parameter under significant destabilizing influence
      from the cross terms. On the other, they also allude to the possibility that in
      real systems, these complexities might indeed be inhibiting the formation of a
      low-temperature biaxial order itself-perhaps reflecting the difficulties in their
      ready realization in the laboratory.

PMID- 29346960
TI  - Chimera and modulated drift states in a ring of nonlocally coupled oscillators
      with heterogeneous phase lags.
AB  - We consider a ring of phase oscillators with nonlocal coupling strength and
      heterogeneous phase lags. We analyze the effects of heterogeneity in the phase
      lags on the existence and stability of a variety of steady states. A nonlocal
      coupling with heterogeneous phase lags that allows the system to be solved
      analytically is suggested and the stability of solutions along the Ott-Antonsen
      invariant manifold is explored. We present a complete bifurcation diagram for
      stationary patterns including the uniform drift and modulated drift states as
      well as chimera state, which reveals that the stable modulated drift state and a
      continuum of metastable drift states could occur due to the heterogeneity of the
      phase lags. We verify our theoretical results using the direct numerical
      simulations of the model system.

PMID- 29346961
TI  - Photonic band structure of diamond colloidal crystals in a cholesteric liquid
      crystal.
AB  - In this paper, we demonstrate the presence of a photonic band gap for a diamond
      lattice structure made of particles with normal anchoring inside a cholesteric
      liquid crystal. As is typical for liquid crystals (LCs), there is considerable
      contrast between the dielectric constant parallel epsilon_{?} and perpendicular
      epsilon_{?} to the director, with epsilon_{?}/epsilon_{?}~4 here. It is shown
      that the size of the photonic band gap is directly related to the size of
      colloidal particles and the contrast between the dielectric constant in the
      particles and the extreme values of epsilon in the LC medium (one needs either
      epsilon in the particle much smaller than epsilon_{?} or much bigger than
      epsilon_{?}). No opening is seen in the band diagrams for small particles. For
      larger particles a partial gap opens when the particles are composed of very low
      dielectric material but never a complete gap. On the other hand, a complete gap
      starts to be revealed when the size of the colloidal particles is increased and
      when a high dielectric constant is used for filling inside the particles. The
      maximum size of the gap is observed when the particles are large enough so that
      their surfaces overlap.

PMID- 29346962
TI  - Osmotic mechanism of the loop extrusion process.
AB  - The loop extrusion theory assumes that protein factors, such as cohesin rings,
      act as molecular motors that extrude chromatin loops. However, recent single
      molecule experiments have shown that cohesin does not show motor activity. To
      predict the physical mechanism involved in loop extrusion, we here theoretically
      analyze the dynamics of cohesin rings on a loop, where a cohesin loader is in the
      middle and unloaders at the ends. Cohesin monomers bind to the loader rather
      frequently and cohesin dimers bind to this site only occasionally. Our theory
      predicts that a cohesin dimer extrudes loops by the osmotic pressure of cohesin
      monomers on the chromatin fiber between the two connected rings. With this
      mechanism, the frequency of the interactions between chromatin segments depends
      on the loading and unloading rates of dimers at the corresponding sites.

PMID- 29346963
TI  - Publisher's Note: Oscillatory motion of a camphor grain in a one-dimensional
      finite region [Phys. Rev. E 94, 042215 (2016)].
AB  - This corrects the article DOI: 10.1103/PhysRevE.94.042215.

PMID- 29346964
TI  - Predictability of fat-tailed extremes.
AB  - We conjecture for a linear stochastic differential equation that the
      predictability of threshold exceedances (I) improves with the event magnitude
      when the noise is a so-called correlated additive-multiplicative noise, no matter
      the nature of the stochastic innovations, and also improves when (II) the noise
      is purely additive, obeying a distribution that decays fast, i.e., not by a power
      law, and (III) deteriorates only when the additive noise distribution follows a
      power law. The predictability is measured by a summary index of the receiver
      operating characteristic curve. We provide support to our conjecture-to
      compliment reports in the existing literature on (II)-by a set of case studies.
      Calculations for the prediction skill are conducted in some cases by a direct
      numerical time-series-data-driven approach and in other cases by an analytical or
      semianalytical approach developed here.

PMID- 29346965
TI  - Solute-mediated interactions between active droplets.
AB  - Concentration gradients play a critical role in embryogenesis, bacterial
      locomotion, as well as the motility of active particles. Particles develop
      concentration profiles around them by dissolution, adsorption, or the reactivity
      of surface species. These gradients change the surface energy of the particles,
      driving both their self-propulsion and governing their interactions. Here, we
      uncover a regime in which solute gradients mediate interactions between slowly
      dissolving droplets without causing autophoresis. This decoupling allows us to
      directly measure the steady-state, repulsive force, which scales with
      interparticle distance as F~1/r^{2}. Our results show that the dissolution
      process is diffusion rather than reaction rate limited, and the theoretical model
      captures the dependence of the interactions on droplet size and solute
      concentration, using a single fit parameter, l=16+/-3nm, which corresponds to the
      length scale of a swollen micelle. Our results shed light on the out-of
      equilibrium behavior of particles with surface reactivity.

PMID- 29346966
TI  - Systematic dimensionality reduction for continuous-time quantum walks of
      interacting fermions.
AB  - To extend the continuous-time quantum walk (CTQW) to simulate P distinguishable
      particles on a graph G composed of N vertices, the Hamiltonian of the system is
      expanded to act on an N^{P}-dimensional Hilbert space, in effect, simulating the
      multiparticle CTQW on graph G via a single-particle CTQW propagating on the
      Cartesian graph product G^{?P}. The properties of the Cartesian graph product
      have been well studied, and classical simulation of multiparticle CTQWs are
      common in the literature. However, the above approach is generally applied as is
      when simulating indistinguishable particles, with the particle statistics then
      applied to the propagated N^{P} state vector to determine walker probabilities.
      We address the following question: How can we modify the underlying graph
      structure G^{?P} in order to simulate multiple interacting fermionic CTQWs with a
      reduction in the size of the state space? In this paper, we present an algorithm
      for systematically removing "redundant" and forbidden quantum states from
      consideration, which provides a significant reduction in the effective dimension
      of the Hilbert space of the fermionic CTQW. As a result, as the number of
      interacting fermions in the system increases, the classical computational
      resources required no longer increases exponentially for fixed N.

PMID- 29346967
TI  - Surface contact charging.
AB  - Experiments in several laboratories have demonstrated that identical materials
      brought into repeated contact generate unexplained and growing surface charge
      domains. Here we show that the growth of charge from these experiments can be
      fitted to a previously developed first-principles model for contact charging
      based on feedback of random surface polarizations. Surprisingly this mechanism,
      which leads to exponential growth in colliding granular beds, can also explain
      nonexponential growth of surface charging, as well as predicting spatiotemporal
      growth of charge domains and their dependencies on material parameters.

PMID- 29346968
TI  - Scaling behavior of thin films on chemically heterogeneous walls.
AB  - We study the adsorption of a fluid in the grand canonical ensemble occurring at a
      planar heterogeneous wall which is decorated with a chemical stripe of width L.
      We suppose that the material of the stripe strongly preferentially adsorbs the
      liquid in contrast to the outer material which is only partially wet. This
      competition leads to the nucleation of a droplet of liquid on the stripe, the
      height h_{m} and shape of which (at bulk two-phase coexistence) has been
      predicted previously using mesoscopic interfacial Hamiltonian theory. We test
      these predictions using a microscopic Fundamental Measure Density Functional
      Theory which incorporates short-ranged fluid-fluid and fully long-ranged wall
      fluid interactions. Our model functional accurately describes packing effects not
      captured by the interfacial Hamiltonian but still we show that there is excellent
      agreement with the predictions h_{m}~L^{1/2} and for the scaled circular shape of
      the drop even for L as small as 50 molecular diameters. For smaller stripes the
      droplet height is considerably lower than that predicted by the mesoscopic
      interfacial theory. Phase transitions for droplet configurations occurring on
      substrates with multiple stripes are also discussed.

PMID- 29346969
TI  - Fitness voter model: Damped oscillations and anomalous consensus.
AB  - We study the dynamics of opinion formation in a heterogeneous voter model on a
      complete graph, in which each agent is endowed with an integer fitness parameter
      k>=0, in addition to its + or - opinion state. The evolution of the distribution
      of k-values and the opinion dynamics are coupled together, so as to allow the
      system to dynamically develop heterogeneity and memory in a simple way. When two
      agents with different opinions interact, their k-values are compared, and with
      probability p the agent with the lower value adopts the opinion of the one with
      the higher value, while with probability 1-p the opposite happens. The agent that
      keeps its opinion (winning agent) increments its k-value by one. We study the
      dynamics of the system in the entire 0<=p<=1 range and compare with the case
      p=1/2, in which opinions are decoupled from the k-values and the dynamics is
      equivalent to that of the standard voter model. When 0<=p<1/2, agents with higher
      k-values are less persuasive, and the system approaches exponentially fast to the
      consensus state of the initial majority opinion. The mean consensus time tau
      appears to grow logarithmically with the number of agents N, and it is greatly
      decreased relative to the linear behavior tau~N found in the standard voter
      model. When 1/2<p<=1, agents with higher k-values are more persuasive, and the
      system initially relaxes to a state with an even coexistence of opinions, but
      eventually reaches consensus by finite-size fluctuations. The approach to the
      coexistence state is monotonic for 1/2<p<p_{o}?0.8, while for p_{o}<=p<=1 there
      are damped oscillations around the coexistence value. The final approach to
      coexistence is approximately a power law t^{-b(p)} in both regimes, where the
      exponent b increases with p. Also, tau increases respect to the standard voter
      model, although it still scales linearly with N. The p=1 case is special, with a
      relaxation to coexistence that scales as t^{-2.73} and a consensus time that
      scales as tau~N^{beta}, with beta?1.45.

PMID- 29346970
TI  - Evoking prescribed spike times in stochastic neurons.
AB  - Single cell stimulation in vivo is a powerful tool to investigate the properties
      of single neurons and their functionality in neural networks. We present a method
      to determine a cell-specific stimulus that reliably evokes a prescribed spike
      train with high temporal precision of action potentials. We test the performance
      of this stimulus in simulations for two different stochastic neuron models. For a
      broad range of parameters and a neuron firing with intermediate firing rates (20
      40 Hz) the reliability in evoking the prescribed spike train is close to its
      theoretical maximum that is mainly determined by the level of intrinsic noise.

PMID- 29346971
TI  - Drag force in a cold or hot granular medium.
AB  - We measure experimentally and analyze the resisting force exerted by a
      bidimensional packing of small disks on a larger intruder disk dragged
      horizontally at constant velocity V_{0}. Depending on the vibration level of the
      packing that leads to a granular "cold" or "hot" packing, two force regimes are
      observed. At low vibration level ("cold" granular medium), the drag force F does
      not depend on V_{0}, whereas for high vibrations ("hot" granular medium), the
      drag force increases linearly with V_{0}. Both regimes can be understood by the
      balance of two "granular temperatures" that can be defined in the system: a bulk
      temperature T_{b} imposed by the external vibration to the overall packing and a
      local temperature T_{0} induced by the own motion of the intruder disk in its
      vicinity. All experimental data obtained for different sizes and velocities of
      the intruder disk are shown to be governed by the temperature ratio T_{0}/T_{b}.
      A critical velocity V_{0c}, above which the system switches from "hot" to "cold,"
      can be obtained in this frame. Finally, we discuss how these two "viscous"
      regimes should be followed by an inertial regime where the drag force F should
      increase as V_{0}^{2} at high enough velocity values, for V_{0} greater than a
      critical value V_{0i} corresponding to high enough Reynolds or Froude number.

PMID- 29346972
TI  - Recursive regularization step for high-order lattice Boltzmann methods.
AB  - A lattice Boltzmann method (LBM) with enhanced stability and accuracy is
      presented for various Hermite tensor-based lattice structures. The collision
      operator relies on a regularization step, which is here improved through a
      recursive computation of nonequilibrium Hermite polynomial coefficients. In
      addition to the reduced computational cost of this procedure with respect to the
      standard one, the recursive step allows to considerably enhance the stability and
      accuracy of the numerical scheme by properly filtering out second- (and higher-)
      order nonhydrodynamic contributions in under-resolved conditions. This is first
      shown in the isothermal case where the simulation of the doubly periodic shear
      layer is performed with a Reynolds number ranging from 10^{4} to 10^{6}, and
      where a thorough analysis of the case at Re=3*10^{4} is conducted. In the latter,
      results obtained using both regularization steps are compared against the
      Bhatnagar-Gross-Krook LBM for standard (D2Q9) and high-order (D2V17 and D2V37)
      lattice structures, confirming the tremendous increase of stability range of the
      proposed approach. Further comparisons on thermal and fully compressible flows,
      using the general extension of this procedure, are then conducted through the
      numerical simulation of Sod shock tubes with the D2V37 lattice. They confirm the
      stability increase induced by the recursive approach as compared with the
      standard one.

PMID- 29346973
TI  - Generalized model for k-core percolation and interdependent networks.
AB  - Cascading failures in complex systems have been studied extensively using two
      different models: k-core percolation and interdependent networks. We combine the
      two models into a general model, solve it analytically, and validate our
      theoretical results through extensive simulations. We also study the complete
      phase diagram of the percolation transition as we tune the average local k-core
      threshold and the coupling between networks. We find that the phase diagram of
      the combined processes is very rich and includes novel features that do not
      appear in the models studying each of the processes separately. For example, the
      phase diagram consists of first- and second-order transition regions separated by
      two tricritical lines that merge and enclose a two-stage transition region. In
      the two-stage transition, the size of the giant component undergoes a first-order
      jump at a certain occupation probability followed by a continuous second-order
      transition at a lower occupation probability. Furthermore, at certain fixed
      interdependencies, the percolation transition changes from first-order -> second
      order -> two-stage -> first-order as the k-core threshold is increased. The
      analytic equations describing the phase boundaries of the two-stage transition
      region are set up, and the critical exponents for each type of transition are
      derived analytically.

PMID- 29346974
TI  - Additional energy-information relations in thermodynamics of small systems.
AB  - The Clausius inequality form of the second law of thermodynamics relates
      information changes (entropy) to changes in the first moment of the energy (heat
      and indirectly also work). Are there similar relations between other moments of
      the energy distribution, and other information measures, or is the Clausius
      inequality a one of a kind instance of the energy-information paradigm? If there
      are additional relations, can they be used to make predictions on measurable
      quantities? Changes in the energy distribution beyond the first moment (average
      heat or work) are especially important in small systems which are often very far
      from thermal equilibrium. The additional energy-information relations (AEIR's),
      here derived, provide positive answers to the two questions above and add another
      layer to the fundamental connection between energy and information. To illustrate
      the utility of the new AEIR's, we find scenarios where the AEIR's yield tighter
      constraints on performance (e.g., in thermal machines) compared to the second
      law. To obtain the AEIR's we use the Bregman divergence-a mathematical tool found
      to be highly suitable for energy-information studies. The quantum version of the
      AEIR's provides a thermodynamic meaning to various quantum coherence measures. It
      is intriguing to fully map the regime of validity of the AEIR's and extend the
      present results to more general scenarios including continuous systems and
      particles exchange with the baths.

PMID- 29346975
TI  - Cycle-expansion method for the Lyapunov exponent, susceptibility, and higher
      moments.
AB  - Lyapunov exponents characterize the chaotic nature of dynamical systems by
      quantifying the growth rate of uncertainty associated with the imperfect
      measurement of initial conditions. Finite-time estimates of the exponent,
      however, experience fluctuations due to both the initial condition and the
      stochastic nature of the dynamical path. The scale of these fluctuations is
      governed by the Lyapunov susceptibility, the finiteness of which typically
      provides a sufficient condition for the law of large numbers to apply. Here, we
      obtain a formally exact expression for this susceptibility in terms of the Ruelle
      dynamical zeta function for one-dimensional systems. We further show that, for
      systems governed by sequences of random matrices, the cycle expansion of the zeta
      function enables systematic computations of the Lyapunov susceptibility and of
      its higher-moment generalizations. The method is here applied to a class of
      dynamical models that maps to static disordered spin chains with interactions
      stretching over a varying distance and is tested against Monte Carlo simulations.

PMID- 29346976
TI  - Correspondence between a noisy sample-space-reducing process and records in
      correlated random events.
AB  - We study survival time statistics in a noisy sample-space-reducing (SSR) process.
      Our simulations suggest that both the mean and standard deviation scale as
      ~N/N^{lambda}, where N is the system size and lambda is a tunable parameter that
      characterizes the process. The survival time distribution has the form
      P_{N}(tau)~N^{-theta}J(tau/N^{theta}), where J is a universal scaling function
      and theta=1-lambda. Analytical insight is provided by a conjecture for the
      equivalence between the survival time statistics in the noisy SSR process and the
      record statistics in a correlated time series modeled as a drifted random walk
      with Cauchy distributed jumps.

PMID- 29346977
TI  - Dynamical ion transfer between coupled Coulomb crystals in a double-well
      potential.
AB  - We investigate the nonequilibrium dynamics of coupled Coulomb crystals of
      different sizes trapped in a double well potential. The dynamics is induced by an
      instantaneous quench of the potential barrier separating the two crystals. Due to
      the intra- and intercrystal Coulomb interactions and the asymmetric population of
      the potential wells, we observe a complex reordering of ions within the two
      crystals as well as ion transfer processes from one well to the other. The study
      and analysis of the latter processes constitutes the main focus of this work. In
      particular, we examine the dependence of the observed ion transfers on the quench
      amplitude performing an analysis for different crystalline configurations ranging
      from one-dimensional ion chains via two-dimensional zigzag chains and ring
      structures to three-dimensional spherical structures. Such an analysis provides
      us with the means to extract the general principles governing the ion transfer
      dynamics and we gain some insight on the structural disorder caused by the quench
      of the barrier height.

PMID- 29346978
TI  - Heating without heat: Thermodynamics of passive energy filters between finite
      systems.
AB  - Passive filters allowing the exchange of particles in a narrow band of energy are
      currently used in microrefrigerators and energy transducers. In this Rapid
      Communication, we analyze their thermal properties using linear irreversible
      thermodynamics and kinetic theory, and discuss a striking phenomenon: the
      possibility of simultaneously increasing or decreasing the temperatures of two
      systems without any supply of energy. This occurs when the filter induces a flow
      of particles whose energy is between the average energies of the two systems.
      Here we show that this selective transfer of particles does not need the action
      of any sort of Maxwell demon and can be carried out by passive filters without
      compromising the second law of thermodynamics. This phenomenon allows us to
      design cycles between two reservoirs at temperatures T_{1}<T_{2} that are able to
      reach temperatures below T_{1} or above T_{2}.

PMID- 29346979
TI  - Variational formulation of a quantitative phase-field model for nonisothermal
      solidification in a multicomponent alloy.
AB  - A variational formulation of a quantitative phase-field model is presented for
      nonisothermal solidification in a multicomponent alloy with two-sided asymmetric
      diffusion. The essential ingredient of this formulation is that the diffusion
      fluxes for conserved variables in both the liquid and solid are separately
      derived from functional derivatives of the total entropy and then these fluxes
      are related to each other on the basis of the local equilibrium conditions. In
      the present formulation, the cross-coupling terms between the phase-field and
      conserved variables naturally arise in the phase-field equation and diffusion
      equations, one of which corresponds to the antitrapping current, the
      phenomenological correction term in early nonvariational models. In addition,
      this formulation results in diffusivities of tensor form inside the interface.
      Asymptotic analysis demonstrates that this model can exactly reproduce the free
      boundary problem in the thin-interface limit. The present model is widely
      applicable because approximations and simplifications are not formally introduced
      into the bulk's free energy densities and because off-diagonal elements of the
      diffusivity matrix are explicitly taken into account. Furthermore, we propose a
      nonvariational form of the present model to achieve high numerical performance. A
      numerical test of the nonvariational model is carried out for nonisothermal
      solidification in a binary alloy. It shows fast convergence of the results with
      decreasing interface thickness.

PMID- 29346980
TI  - Fractional cable equation for general geometry: A model of axons with swellings
      and anomalous diffusion.
AB  - Different experimental studies have reported anomalous diffusion in brain tissues
      and notably this anomalous diffusion is expressed through fractional derivatives.
      Axons are important to understand neurodegenerative diseases such as multiple
      sclerosis, Alzheimer's disease, and Parkinson's disease. Indeed, abnormal
      accumulation of proteins and organelles in axons is a hallmark of these diseases.
      The diffusion in the axons can become anomalous as a result of this abnormality.
      In this case the voltage propagation in axons is affected. Another hallmark of
      different neurodegenerative diseases is given by discrete swellings along the
      axon. In order to model the voltage propagation in axons with anomalous diffusion
      and swellings, in this paper we propose a fractional cable equation for a general
      geometry. This generalized equation depends on fractional parameters and
      geometric quantities such as the curvature and torsion of the cable. For a cable
      with a constant radius we show that the voltage decreases when the fractional
      effect increases. In cables with swellings we find that when the fractional
      effect or the swelling radius increases, the voltage decreases. Similar behavior
      is obtained when the number of swellings and the fractional effect increase.
      Moreover, we find that when the radius swelling (or the number of swellings) and
      the fractional effect increase at the same time, the voltage dramatically
      decreases.

PMID- 29346982
TI  - Direction-dependent force-induced dissociation dynamics of an entropic-driven
      lock-and-key assembly.
AB  - The unbinding dynamics of a nanosized sphere-and-cavity assembly under the
      pulling of constant force and constant loading rate is explored by dissipative
      particle dynamics simulations. The formation of this matched lock-and-key pair in
      a polymer solution is driven by the depletion attraction. The two-dimensional
      free energy landscape U(x,z) associated with this assembly is constructed. Our
      results indicate that the unbinding pathway along the orientation of the assembly
      is unfavorable due to the relatively high energy barrier compared to that along
      the tortuous minimum path whose energy barrier is not high. It is also found that
      the dissociation rate depends on the direction of the external force (theta) with
      respect to the assembly orientation. The presence of the force component
      perpendicular to the assembly orientation can reduce the bond lifetime
      significantly by driving the key particle to approach the minimum path. Moreover,
      the dissociation dynamics can be facilitated even by a pushing force compared to
      the spontaneous dissociation (without forces). To elucidate the effective pathway
      under pulling, the escaping position is analyzed and its mean direction with
      respect to the assembly orientation rises generally with increasing theta,
      revealing that the presence of the force component along the minimum pathway is
      helpful. The importance of the direction of the external pulling has been
      demonstrated in our simple system. Therefore, this effect should be considered in
      more complicated unbinding experiments.

PMID- 29346983
TI  - Three-dimensional slow Rossby waves in rotating spherical density-stratified
      convection.
AB  - We develop a theory of three-dimensional slow Rossby waves in rotating spherical
      density stratified convection. The Rossby waves, with frequencies which are much
      smaller than the rotating frequency, are excited by a nonaxisymmetric instability
      from the equilibrium based on the developed convection. These waves interact with
      the inertial waves and the density stratified convection. The density
      stratification is taken into account using the anelastic approximation for very
      low-Mach-number flows. We study long-term planetary Rossby waves with periods
      which are larger than two years. We suggest that these waves are related to the
      southern oscillation and El Nino. The El Nino is an irregularly periodical
      variation in winds and sea surface temperatures over the tropical Pacific ocean,
      while the southern oscillation is an oscillation in surface air pressure between
      the tropical eastern and the western Pacific ocean. The strength of the southern
      oscillation is characterized by the southern oscillation index (SOI). The
      developed theory is applied for the interpretation of the observed periods of the
      SOI. This study demonstrates a good agreement between the theoretical predictions
      and the observations.

PMID- 29346981
TI  - Model for screened, charge-regulated electrostatics of an eye lens protein:
      Bovine gammaB-crystallin.
AB  - We model screened, site-specific charge regulation of the eye lens protein bovine
      gammaB-crystallin (gammaB) and study the probability distributions of its proton
      occupancy patterns. Using a simplified dielectric model, we solve the linearized
      Poisson-Boltzmann equation to calculate a 54*54 work-of-charging matrix, each
      entry being the modeled voltage at a given titratable site, due to an elementary
      charge at another site. The matrix quantifies interactions within patches of
      sites, including gammaB charge pairs. We model intrinsic pK values that would
      occur hypothetically in the absence of other charges, with use of experimental
      data on the dependence of pK values on aqueous solution conditions, the
      dielectric model, and literature values. We use Monte Carlo simulations to
      calculate a model grand-canonical partition function that incorporates both the
      work-of-charging and the intrinsic pK values for isolated gammaB molecules and we
      calculate the probabilities of leading proton occupancy configurations, for
      4<pH<8 and Debye screening lengths from 6 to 20 A. We select the interior
      dielectric value to model gammaB titration data. At pH 7.1 and Debye length 6.0
      A, on a given gammaB molecule the predicted top occupancy pattern is present
      nearly 20% of the time, and 90% of the time one or another of the first 100
      patterns will be present. Many of these occupancy patterns differ in net charge
      sign as well as in surface voltage profile. We illustrate how charge pattern
      probabilities deviate from the multinomial distribution that would result from
      use of effective pK values alone and estimate the extents to which gammaB charge
      pattern distributions broaden at lower pH and narrow as ionic strength is
      lowered. These results suggest that for accurate modeling of orientation
      dependent gammaB-gammaB interactions, consideration of numerous pairs of proton
      occupancy patterns will be needed.

PMID- 29346984
TI  - Mechanical failure in amorphous solids: Scale-free spinodal criticality.
AB  - The mechanical failure of amorphous media is a ubiquitous phenomenon from
      material engineering to geology. It has been noticed for a long time that the
      phenomenon is "scale-free," indicating some type of criticality. In spite of
      attempts to invoke "Self-Organized Criticality," the physical origin of this
      criticality, and also its universal nature, being quite insensitive to the nature
      of microscopic interactions, remained elusive. Recently we proposed that the
      precise nature of this critical behavior is manifested by a spinodal point of a
      thermodynamic phase transition. Demonstrating this requires the introduction of
      an "order parameter" that is suitable for distinguishing between disordered
      amorphous systems. At the spinodal point there exists a divergent correlation
      length which is associated with the system-spanning instabilities (known also as
      shear bands) which are typical to the mechanical yield. The theory, the order
      parameter used and the correlation functions which exhibit the divergent
      correlation length are universal in nature and can be applied to any amorphous
      solid that undergoes mechanical yield. The phenomenon is seen at its sharpest in
      athermal systems, as is explained below; in this paper we extend the discussion
      also to thermal systems, showing that at sufficiently high temperatures the
      spinodal phenomenon is destroyed by thermal fluctuations.

PMID- 29346985
TI  - Three faces of entropy for complex systems: Information, thermodynamics, and the
      maximum entropy principle.
AB  - There are at least three distinct ways to conceptualize entropy: entropy as an
      extensive thermodynamic quantity of physical systems (Clausius, Boltzmann,
      Gibbs), entropy as a measure for information production of ergodic sources
      (Shannon), and entropy as a means for statistical inference on multinomial
      processes (Jaynes maximum entropy principle). Even though these notions represent
      fundamentally different concepts, the functional form of the entropy for
      thermodynamic systems in equilibrium, for ergodic sources in information theory,
      and for independent sampling processes in statistical systems, is degenerate,
      H(p)=-?_{i}p_{i}logp_{i}. For many complex systems, which are typically history
      dependent, nonergodic, and nonmultinomial, this is no longer the case. Here we
      show that for such processes, the three entropy concepts lead to different
      functional forms of entropy, which we will refer to as S_{EXT} for extensive
      entropy, S_{IT} for the source information rate in information theory, and
      S_{MEP} for the entropy functional that appears in the so-called maximum entropy
      principle, which characterizes the most likely observable distribution functions
      of a system. We explicitly compute these three entropy functionals for three
      concrete examples: for Polya urn processes, which are simple self-reinforcing
      processes, for sample-space-reducing (SSR) processes, which are simple history
      dependent processes that are associated with power-law statistics, and finally
      for multinomial mixture processes.

PMID- 29346986
TI  - Unifying perspective: Solitary traveling waves as discrete breathers in
      Hamiltonian lattices and energy criteria for their stability.
AB  - In this work, we provide two complementary perspectives for the (spectral)
      stability of solitary traveling waves in Hamiltonian nonlinear dynamical
      lattices, of which the Fermi-Pasta-Ulam and the Toda lattice are prototypical
      examples. One is as an eigenvalue problem for a stationary solution in a
      cotraveling frame, while the other is as a periodic orbit modulo shifts. We
      connect the eigenvalues of the former with the Floquet multipliers of the latter
      and using this formulation derive an energy-based spectral stability criterion.
      It states that a sufficient (but not necessary) condition for a change in the
      wave stability occurs when the functional dependence of the energy (Hamiltonian)
      H of the model on the wave velocity c changes its monotonicity. Moreover, near
      the critical velocity where the change of stability occurs, we provide an
      explicit leading-order computation of the unstable eigenvalues, based on the
      second derivative of the Hamiltonian H^{''}(c_{0}) evaluated at the critical
      velocity c_{0}. We corroborate this conclusion with a series of analytically and
      numerically tractable examples and discuss its parallels with a recent energy
      based criterion for the stability of discrete breathers.

PMID- 29346987
TI  - Characterizing pixel and point patterns with a hyperuniformity disorder length.
AB  - We introduce the concept of a "hyperuniformity disorder length" h that controls
      the variance of volume fraction fluctuations for randomly placed windows of fixed
      size. In particular, fluctuations are determined by the average number of
      particles within a distance h from the boundary of the window. We first compute
      special expectations and bounds in d dimensions, and then illustrate the range of
      behavior of h versus window size L by analyzing several different types of
      simulated two-dimensional pixel patterns-where particle positions are stored as a
      binary digital image in which pixels have value zero if empty and one if they
      contain a particle. The first are random binomial patterns, where pixels are
      randomly flipped from zero to one with probability equal to area fraction. These
      have long-ranged density fluctuations, and simulations confirm the exact result
      h=L/2. Next we consider vacancy patterns, where a fraction f of particles on a
      lattice are randomly removed. These also display long-range density fluctuations,
      but with h=(L/2)(f/d) for small f, and h=L/2 for f->1. And finally, for a
      hyperuniform system with no long-range density fluctuations, we consider
      "Einstein patterns," where each particle is independently displaced from a
      lattice site by a Gaussian-distributed amount. For these, at large L,h approaches
      a constant equal to about half the root-mean-square displacement in each
      dimension. Then we turn to gray-scale pixel patterns that represent simulated
      arrangements of polydisperse particles, where the volume of a particle is encoded
      in the value of its central pixel. And we discuss the continuum limit of point
      patterns, where pixel size vanishes. In general, we thus propose to quantify
      particle configurations not just by the scaling of the density fluctuation
      spectrum but rather by the real-space spectrum of h(L) versus L. We call this
      approach "hyperuniformity disorder length spectroscopy".

PMID- 29346988
TI  - Liquid part of the phase diagram and percolation line for two-dimensional
      Mercedes-Benz water.
AB  - Monte Carlo simulations and Wertheim's thermodynamic perturbation theory (TPT)
      are used to predict the phase diagram and percolation curve for the simple two
      dimensional Mercedes-Benz (MB) model of water. The MB model of water is quite
      popular for explaining water properties, but the phase diagram has not been
      reported till now. In the MB model, water molecules are modeled as two
      dimensional Lennard-Jones disks, with three orientation-dependent hydrogen
      bonding arms, arranged as in the MB logo. The liquid part of the phase space is
      explored using grand canonical Monte Carlo simulations and two versions of
      Wertheim's TPT for associative fluids, which have been used before to predict the
      properties of the simple MB model. We find that the theory reproduces well the
      physical properties of hot water but is less successful at capturing the more
      structured hydrogen bonding that occurs in cold water. In addition to reporting
      the phase diagram and percolation curve of the model, it is shown that the
      improved TPT predicts the phase diagram rather well, while the standard one
      predicts a phase transition at lower temperatures. For the percolation line, both
      versions have problems predicting the correct position of the line at high
      temperatures.

PMID- 29346989
TI  - Generation of droplet arrays with rational number spacing patterns driven by a
      periodic energy landscape.
AB  - The generation of droplets at low Reynolds numbers is driven by nonlinear
      dynamics that give rise to complex patterns concerning both the droplet-to
      droplet spacing and the individual droplet sizes. Here we demonstrate an
      experimental system in which a time-varying energy landscape provides a periodic
      magnetic force that generates an array of droplets from an immiscible mixture of
      ferrofluid and silicone oil. The resulting droplet patterns are periodic, owing
      to the nature of the magnetic force, yet the droplet spacing and size can vary
      greatly by tuning a single bias pressure applied on the ferrofluid phase; for a
      given cycle period of the magnetic force, droplets can be generated either at
      integer multiples (1, 2, ...), or at rational fractions (3/2, 5/3, 5/2, ...) of
      this period with mono- or multidisperse droplet sizes. We develop a discrete-time
      dynamical systems model not only to reproduce the phenotypes of the observed
      patterns but also to provide a framework for understanding systems driven by such
      periodic energy landscapes.

PMID- 29346990
TI  - Critical noise can make the minority candidate win: The U.S. presidential
      election cases.
AB  - A national voting population, when segmented into groups such as, for example,
      different states, can yield a counterintuitive scenario in which the winner may
      not necessarily get the highest number of total votes. A recent example is the
      2016 presidential election in the United States. We model the situation by using
      interacting opinion dynamics models, and we look at the effect of coarse graining
      near the critical points where the spatial fluctuations are high. We establish
      that the sole effect of coarse graining, which mimics the "winner take all"
      electoral college system in the United States, can give rise to finite
      probabilities of events in which a minority candidate wins even in the large size
      limit near the critical point. The overall probabilities of victory of the
      minority candidate can be predicted from the models, which indicate that one may
      expect more instances of minority candidate winning in the future.

PMID- 29346991
TI  - Universal scaling of the stress-strain curve in amorphous solids.
AB  - The yielding transition of amorphous solids is a phase transition with a special
      type of universality. Critical exponents and scaling relations have been defined
      and proposed near the yield stress. We show here that, even in the initial stage
      of shear far below the yield stress, the stress-strain curve of amorphous solids
      also shows critical scaling with universal exponents. The key point is to remove
      the elastic part of the strain, and the shear stress exhibits a sublinear scaling
      with the plastic strain. We show how this critical scaling is related to the
      finite size effect of the minimum strain to trigger the first plastic avalanche
      after a quench. We point out that this sublinear scaling between the stress and
      the plastic strain implies the divergence of a high-order shear modulus. A
      scaling relation is derived between two exponents characterizing the stress
      strain curve and the density distribution of the local stabilities, respectively.
      We test the critical scaling of the stress-strain curve using both mesoscopic and
      atomistic simulations and get satisfying agreement in two and three dimensions.

PMID- 29346992
TI  - Existence and construction of large stable food webs.
AB  - Ecological diversity is ubiquitous despite the restrictions imposed by
      competitive exclusion and apparent competition. To explain the observed richness
      of species in a given habitat, food-web theory has explored nonlinear functional
      responses, self-interaction, or spatial structure and dispersal-model ingredients
      that have proven to promote stability and diversity. We return instead here to
      classical Lotka-Volterra equations, where species-species interaction is
      characterized by a simple product and spatial restrictions are ignored. We
      quantify how this idealization imposes constraints on coexistence and diversity
      for many species. To this end, we introduce the concept of free and controlled
      species and use this to demonstrate how stable food webs can be constructed by
      the sequential addition of species. The resulting food webs can reach dozens of
      species and generally yield nonrandom degree distributions in accordance with the
      constraints imposed through the assembly process. Our model thus serves as a
      formal starting point for the study of sustainable interaction patterns between
      species.

PMID- 29346993
TI  - Vibrational resonance in an inhomogeneous medium with periodic dissipation.
AB  - The role of nonlinear dissipation in vibrational resonance (VR) is investigated
      in an inhomogeneous system characterized by a symmetric and spatially periodic
      potential and subjected to nonuniform state-dependent damping and a biharmonic
      driving force. The contributions of the parameters of the high-frequency signal
      to the system's effective dissipation are examined theoretically in comparison to
      linearly damped systems, for which the parameter of interest is the effective
      stiffness in the equation of slow vibration. We show that the VR effect can be
      enhanced by varying the nonlinear dissipation parameters and that it can be
      induced by a parameter that is shared by the damping inhomogeneity and the system
      potential. Furthermore, we have apparently identified the origin of the nonlinear
      dissipation-enhanced response: We provide evidence of its connection to a Hopf
      bifurcation, accompanied by monotonic attractor enlargement in the VR regime.

PMID- 29346994
TI  - Weakly non-Boussinesq convection in a gaseous spherical shell.
AB  - We examine the dynamics associated with weakly compressible convection in a
      spherical shell by running 3D direct numerical simulations using the Boussinesq
      formalism [Spiegel and Veronis, Astrophys. J. 131, 442 (1960)AJLEEY0004
      637X10.1086/146849]. Motivated by problems in astrophysics, we assume the
      existence of a finite adiabatic temperature gradient ?T_{ad} and use mixed
      boundary conditions for the temperature with fixed flux at the inner boundary and
      fixed temperature at the outer boundary. This setup is intrinsically more
      asymmetric than the more standard case of Rayleigh-Benard convection in liquids
      between parallel plates with fixed temperature boundary conditions. Conditions
      where there is substantial asymmetry can cause a dramatic change in the nature of
      convection and we demonstrate that this is the case here. The flows can become
      pressure- rather than buoyancy-dominated, leading to anomalous heat transport by
      upflows. Counterintuitively, the background temperature gradient ?T[over -] can
      develop a subadiabatic layer (where g.?T[over -]<g.?T_{ad}, where g is gravity)
      although convection remains vigorous at every point across the shell. This
      indicates a high degree of nonlocality.

PMID- 29346995
TI  - Difference between memory and prediction in linear recurrent networks.
AB  - Recurrent networks are trained to memorize their input better, often in the hopes
      that such training will increase the ability of the network to predict. We show
      that networks designed to memorize input can be arbitrarily bad at prediction. We
      also find, for several types of inputs, that one-node networks optimized for
      prediction are nearly at upper bounds on predictive capacity given by Wiener
      filters and are roughly equivalent in performance to randomly generated five-node
      networks. Our results suggest that maximizing memory capacity leads to very
      different networks than maximizing predictive capacity and that optimizing
      recurrent weights can decrease reservoir size by half an order of magnitude.

PMID- 29346996
TI  - Particle rearrangement and softening contributions to the nonlinear mechanical
      response of glasses.
AB  - Amorphous materials such as metallic, polymeric, and colloidal glasses exhibit
      complex preparation-dependent mechanical response to applied shear. In
      particular, glassy solids yield, with a mechanical response that transitions from
      elastic to plastic, with increasing shear strain. We perform numerical
      simulations to investigate the mechanical response of binary Lennard-Jones
      glasses undergoing athermal, quasistatic pure shear as a function of the cooling
      rate R used to prepare them. The ensemble-averaged stress versus strain curve
      <sigma(gamma)> resembles the spatial average in the large size limit, which
      appears smooth and displays a putative elastic regime at small strains, a
      yielding-related peak in stress at intermediate strain, and a plastic flow regime
      at large strains. In contrast, for each glass configuration in the ensemble, the
      stress-strain curve sigma(gamma) consists of many short nearly linear segments
      that are punctuated by particle-rearrangement-induced rapid stress drops. To
      explain the nonlinearity of <sigma(gamma)>, we quantify the shape of the small
      stress-strain segments and the frequency and size of the stress drops in each
      glass configuration. We decompose the stress loss [i.e., the deviation in the
      slope of <sigma(gamma)> from that at <sigma(0)>] into the loss from particle
      rearrangements and the loss from softening [i.e., the reduction of the slopes of
      the linear segments in sigma(gamma)], and then compare the two contributions as a
      function of R and gamma. For the current studies, the rearrangement-induced
      stress loss is larger than the softening-induced stress loss, however, softening
      stress losses increase with decreasing cooling rate. We also characterize the
      structure of the potential energy landscape along the strain direction for
      glasses prepared with different R, and observe a dramatic change of the
      properties of the landscape near the yielding transition. We then show that the
      rearrangement-induced energy loss per strain can serve as an order parameter for
      the yielding transition, which sharpens for slow cooling rates and in large
      systems.

PMID- 29346997
TI  - Deformation and buckling of microcapsules in a viscoelastic matrix.
AB  - In this paper, we numerically study the dynamics of (1) a Newtonian liquid-filled
      capsule in a viscoelastic matrix and that of (2) a viscoelastic capsule in a
      Newtonian matrix in a linear shear flow using a front-tracking method. The
      numerical results for case (1) indicate that the polymeric fluid reduces the
      capsule deformation and aligns the deformed capsule with the flow direction. It
      also narrows the range of tension experienced by the deformed capsule for case
      (1), while the tank-treading period significantly increases. Interestingly, the
      polymeric fluid has an opposite effect on the tank-treading period and the
      orientation angle of case (2), but its effect on the deformation is similar to
      case (1).

PMID- 29346998
TI  - Antiferromagnetic Ising model in an imaginary magnetic field.
AB  - We study the two-dimensional antiferromagnetic Ising model with a purely
      imaginary magnetic field, which can be thought of as a toy model for the usual
      theta physics. Our motivation is to have a benchmark calculation in a system
      which suffers from a strong sign problem, so that our results can be used to test
      Monte Carlo methods developed to tackle such problems. We analyze here this model
      by means of analytical techniques, computing exactly the first eight cumulants of
      the expansion of the effective Hamiltonian in powers of the inverse temperature,
      and calculating physical observables for a large number of degrees of freedom
      with the help of standard multiprecision algorithms. We report accurate results
      for the free energy density, internal energy, standard and staggered
      magnetization, and the position and nature of the critical line, which confirm
      the mean-field qualitative picture, and which should be quantitatively reliable,
      at least in the high-temperature regime, including the entire critical line.

PMID- 29346999
TI  - Mean flow produced by small-amplitude vibrations of a liquid bridge with its free
      surface covered with an insoluble surfactant.
AB  - As is well known, confined fluid systems subject to forced vibrations produce
      mean flows, called in this context streaming flows. These mean flows promote an
      overall mass transport in the fluid that has consequences in the transport of
      passive scalars and surfactants, when these are present in a fluid interface.
      Such transport causes surfactant concentration inhomogeneities that are to be
      counterbalanced by Marangoni elasticity. Therefore, the interaction of streaming
      flows and Marangoni convection is expected to produce new flow structures that
      are different from those resulting when only one of these effects is present. The
      present paper focuses on this interaction using the liquid bridge geometry as a
      paradigmatic system for the analysis. Such analysis is based on an appropriate
      post-processing of the results obtained via direct numerical simulation of the
      system for moderately small viscosity, a condition consistent with typical
      experiments of vibrated millimetric liquid bridges. It is seen that the flow
      patterns show a nonmonotone behavior as the Marangoni number is increased. In
      addition, the strength of the mean flow at the free surface exhibits two well
      defined regimes as the forcing amplitude increases. These regimes show fairly
      universal power-law behaviors.

PMID- 29347000
TI  - Pattern production through a chiral chasing mechanism.
AB  - Recent experiments on zebrafish pigmentation suggests that their typical black
      and white striped skin pattern is made up of a number of interacting
      chromatophore families. Specifically, two of these cell families have been shown
      to interact through a nonlocal chasing mechanism, which has previously been
      modeled using integro-differential equations. We extend this framework to include
      the experimentally observed fact that the cells often exhibit chiral movement, in
      that the cells chase, and run away, at angles different to the line connecting
      their centers. This framework is simplified through the use of multiple small
      limits leading to a coupled set of partial differential equations which are
      amenable to Fourier analysis. This analysis results in the production of
      dispersion relations and necessary conditions for a patterning instability to
      occur. Beyond the theoretical development and the production of new pattern
      planiforms we are able to corroborate the experimental hypothesis that the global
      pigmentation patterns can be dependent on the chirality of the chromatophores.

PMID- 29347001
TI  - Universal scaling of the distribution of land in urban areas.
AB  - In this work, we explore the spatial structure of built zones and green areas in
      diverse western cities by analyzing the probability distribution of areas and a
      coefficient that characterize their respective shapes. From the analysis of
      diverse datasets describing land lots in urban areas, we found that the
      distribution of built-up areas and natural zones in cities obey inverse power
      laws with a similar scaling for the cities explored. On the other hand, by
      studying the distribution of shapes of lots in urban regions, we are able to
      detect global differences in the spatial structure of the distribution of land.
      Our findings introduce information about spatial patterns that emerge in the
      structure of urban settlements; this knowledge is useful for the understanding of
      urban growth, to improve existing models of cities, in the context of
      sustainability, in studies about human mobility in urban areas, among other
      applications.

PMID- 29347002
TI  - Work and power fluctuations in a critical heat engine.
AB  - We investigate fluctuations of output work for a class of Stirling heat engines
      with working fluid composed of interacting units and compare these fluctuations
      to an average work output. In particular, we focus on engine performance close to
      a critical point where Carnot's efficiency may be attained at a finite power as
      reported by M. Campisi and R. Fazio [Nat. Commun. 7, 11895 (2016)2041
      172310.1038/ncomms11895]. We show that the variance of work output per cycle
      scales with the same critical exponent as the heat capacity of the working fluid.
      As a consequence, the relative work fluctuation diverges unless the output work
      obeys a rather strict scaling condition, which would be very hard to fulfill in
      practice. Even under this condition, the fluctuations of work and power do not
      vanish in the infinite system size limit. Large fluctuations of output work thus
      constitute inseparable and dominant element in performance of the macroscopic
      heat engines close to a critical point.

PMID- 29347003
TI  - Killing (absorption) versus survival in random motion.
AB  - We address diffusion processes in a bounded domain, while focusing on somewhat
      unexplored affinities between the presence of absorbing and/or inaccessible
      boundaries. For the Brownian motion (Levy-stable cases are briefly mentioned)
      model-independent features are established of the dynamical law that underlies
      the short-time behavior of these random paths, whose overall lifetime is
      predefined to be long. As a by-product, the limiting regime of a permanent
      trapping in a domain is obtained. We demonstrate that the adopted conditioning
      method, involving the so-called Bernstein transition function, works properly
      also in an unbounded domain, for stochastic processes with killing (Feynman-Kac
      kernels play the role of transition densities), provided the spectrum of the
      related semigroup operator is discrete. The method is shown to be useful in the
      case, when the spectrum of the generator goes down to zero and no isolated
      minimal (ground state) eigenvalue is in existence, like in the problem of the
      long-term survival on a half-line with a sink at origin.

PMID- 29347004
TI  - Self-propulsion against a moving membrane: Enhanced accumulation and drag force.
AB  - Self-propulsion (SP) is a main feature of active particles (AP), such as bacteria
      or biological micromotors, distinguishing them from passive colloids. A renowned
      consequence of SP is accumulation at static interfaces, even in the absence of
      hydrodynamic interactions. Here we address the role of SP in the interaction
      between AP and a moving semipermeable membrane. In particular, we implement a
      model of noninteracting AP in a channel crossed by a partially penetrable wall,
      moving at a constant velocity c. With respect to both the cases of passive
      colloids with c>0 and AP with c=0, the AP with finite c show enhancement of
      accumulation in front of the obstacle and experience a largely increased drag
      force. This effect is understood in terms of an effective potential localised at
      the interface between particles and membrane, of height proportional to ctau/xi,
      where tau is the AP's reorientation time and xi the width characterizing the
      surface's smoothness (xi->0 for hard core obstacles). An approximate analytical
      scheme is able to reproduce the observed density profiles and the measured drag
      force, in very good agreement with numerical simulations. The effects discussed
      here can be exploited for automatic selection and filtering of AP with desired
      parameters.

PMID- 29347005
TI  - Universality-class crossover by a nonorder field introduced to the pair contact
      process with diffusion.
AB  - The one-dimensional pair contact process with diffusion (PCPD), an interacting
      particle system with diffusion, pair annihilation, and creation by pairs, has
      defied consensus about the universality class to which it belongs. An argument by
      Hinrichsen [Physica A 361, 457 (2006)PHYADX0378-437110.1016/j.physa.2005.06.101]
      claims that freely diffusing particles in the PCPD should play the same role as
      frozen particles when it comes to the critical behavior. Therefore, the PCPD is
      claimed to have the same critical phenomena as a model with infinitely many
      absorbing states that belongs to the directed percolation (DP) universality
      class. To investigate if diffusing particles are really indistinguishable from
      frozen particles in the sense of the renormalization group, we study numerically
      a variation of the PCPD by introducing a nonorder field associated with
      infinitely many absorbing states. We find that a crossover from the PCPD to DP
      occurs due to the nonorder field. By studying a similar model, we exclude the
      possibility that the mere introduction of a nonorder field to one model can
      entail a nontrivial crossover to another model in the same universality class,
      thus we attribute the observed crossover to the difference of the universality
      class of the PCPD from the DP class.

PMID- 29347006
TI  - Two-time correlation functions and the Lee-Yang zeros for an interacting Bose
      gas.
AB  - Two-time correlation functions of a system of Bose particles are studied. We find
      a relation of zeros of the correlation functions with the Lee-Yang zeros of the
      partition function of the system. The obtained relation gives the possibility to
      observe the Lee-Yang zeros experimentally. A particular case of Bose particles on
      two levels is examined, and zeros of two-time correlation functions and Lee-Yang
      zeros of the partition function of the system are analyzed.

PMID- 29347007
TI  - Critical transitions and perturbation growth directions.
AB  - Critical transitions occur in a variety of dynamical systems. Here we employ
      quantifiers of chaos to identify changes in the dynamical structure of complex
      systems preceding critical transitions. As suitable indicator variables for
      critical transitions, we consider changes in growth rates and directions of
      covariant Lyapunov vectors. Studying critical transitions in several models of
      fast-slow systems, i.e., a network of coupled FitzHugh-Nagumo oscillators, models
      for Josephson junctions, and the Hindmarsh-Rose model, we find that tangencies
      between covariant Lyapunov vectors are a common and maybe generic feature during
      critical transitions. We further demonstrate that this deviation from hyperbolic
      dynamics is linked to the occurrence of critical transitions by using it as an
      indicator variable and evaluating the prediction success through receiver
      operating characteristic curves. In the presence of noise, we find the alignment
      of covariant Lyapunov vectors and changes in finite-time Lyapunov exponents to be
      more successful in announcing critical transitions than common indicator
      variables as, e.g., finite-time estimates of the variance. Additionally, we
      propose a new method for estimating approximations of covariant Lyapunov vectors
      without knowledge of the future trajectory of the system. We find that these
      approximated covariant Lyapunov vectors can also be applied to predict critical
      transitions.

PMID- 29347008
TI  - Erratum: Correlations in suspensions confined between viscoelastic surfaces:
      Noncontact microrheology [Phys. Rev. E 96, 022607 (2017)].
AB  - This corrects the article DOI: 10.1103/PhysRevE.96.022607.

PMID- 29347009
TI  - Evolutionary stability concepts in a stochastic environment.
AB  - Over the past 30 years, evolutionary game theory and the concept of an
      evolutionarily stable strategy have been not only extensively developed and
      successfully applied to explain the evolution of animal behaviors, but also
      widely used in economics and social sciences. Nonetheless, the stochastic
      dynamical properties of evolutionary games in randomly fluctuating environments
      are still unclear. In this study, we investigate conditions for stochastic local
      stability of fixation states and constant interior equilibria in a two-phenotype
      model with random payoffs following pairwise interactions. Based on this model,
      we develop the concepts of stochastic evolutionary stability (SES) and stochastic
      convergence stability (SCS). We show that the condition for a pure strategy to be
      SES and SCS is more stringent than in a constant environment, while the condition
      for a constant mixed strategy to be SES is less stringent than the condition to
      be SCS, which is less stringent than the condition in a constant environment.

PMID- 29347010
TI  - Erratum: Optimization of finite-size errors in finite-temperature calculations of
      unordered phases [Phys. Rev. E 91, 062142 (2015)].
AB  - This corrects the article DOI: 10.1103/PhysRevE.91.062142.

PMID- 29347011
TI  - Luminescence from cavitation bubbles deformed in uniform pressure gradients.
AB  - Presented here are observations that demonstrate how the deformation of
      millimetric cavitation bubbles by a uniform pressure gradient quenches single
      collapse luminescence. Our innovative measurement system captures a broad
      luminescence spectrum (wavelength range, 300-900 nm) from the individual
      collapses of laser-induced bubbles in water. By varying the bubble size, driving
      pressure, and perceived gravity level aboard parabolic flights, we probed the
      limit from aspherical to highly spherical bubble collapses. Luminescence was
      detected for bubbles of maximum radii within the previously uncovered range,
      R_{0}=1.5-6 mm, for laser-induced bubbles. The relative luminescence energy was
      found to rapidly decrease as a function of the bubble asymmetry quantified by the
      anisotropy parameter zeta, which is the dimensionless equivalent of the Kelvin
      impulse. As established previously, zeta also dictates the characteristic
      parameters of bubble-driven microjets. The threshold of zeta beyond which no
      luminescence is observed in our experiment closely coincides with the threshold
      where the microjets visibly pierce the bubble and drive a vapor jet during the
      rebound. The individual fitted blackbody temperatures range between T_{lum}=7000
      and T_{lum}=11500 K but do not show any clear trend as a function of zeta. Time
      resolved measurements using a high-speed photodetector disclose multiple
      luminescence events at each bubble collapse. The averaged full width at half
      maximum of the pulse is found to scale with R_{0} and to range between 10 and 20
      ns.

PMID- 29347012
TI  - Steady diffusion in a drift field: A comparison of large-deviation techniques and
      multiple-scale analysis.
AB  - A particle with internal unobserved states diffusing in a force field will
      generally display effective advection-diffusion. The drift velocity is
      proportional to the mobility averaged over the internal states, or effective
      mobility, while the effective diffusion has two terms. One is of the equilibrium
      type and satisfies an Einstein relation with the effective mobility while the
      other is quadratic in the applied force. In this contribution we present two new
      methods to obtain these results, on the one hand using large deviation techniques
      and on the other by a multiple-scale analysis, and compare the two. We consider
      both systems with discrete internal states and continuous internal states. We
      show that the auxiliary equations in the multiple-scale analysis can also be
      derived in second-order perturbation theory in a large deviation theory of a
      generating function (discrete internal states) or generating functional
      (continuous internal states). We discuss that measuring the two components of the
      effective diffusion give a way to determine kinetic rates from only first and
      second moments of the displacement in steady state.

PMID- 29347013
TI  - Correlations in magnitude series to assess nonlinearities: Application to
      multifractal models and heartbeat fluctuations.
AB  - The correlation properties of the magnitude of a time series are associated with
      nonlinear and multifractal properties and have been applied in a great variety of
      fields. Here we have obtained the analytical expression of the autocorrelation of
      the magnitude series (C_{|x|}) of a linear Gaussian noise as a function of its
      autocorrelation (C_{x}). For both, models and natural signals, the deviation of
      C_{|x|} from its expectation in linear Gaussian noises can be used as an index of
      nonlinearity that can be applied to relatively short records and does not require
      the presence of scaling in the time series under study. In a model of artificial
      Gaussian multifractal signal we use this approach to analyze the relation between
      nonlinearity and multifractallity and show that the former implies the latter but
      the reverse is not true. We also apply this approach to analyze experimental
      data: heart-beat records during rest and moderate exercise. For each individual
      subject, we observe higher nonlinearities during rest. This behavior is also
      achieved on average for the analyzed set of 10 semiprofessional soccer players.
      This result agrees with the fact that other measures of complexity are
      dramatically reduced during exercise and can shed light on its relationship with
      the withdrawal of parasympathetic tone and/or the activation of sympathetic
      activity during physical activity.

PMID- 29347014
TI  - Imperfections, impacts, and the singularity of Euler's disk.
AB  - The motion of a rigid, spinning disk on a flat surface ends with a dissipation
      induced finite-time singularity. The problem of finding the dominant energy
      absorption mechanism during the last phase of the motion generated a lively
      debate during the past two decades. Various candidates including air drag and
      different types of friction have been considered, nevertheless impacts have not
      been examined until now. We investigate the effect of impacts caused by geometric
      imperfections of the disk and of the underlying flat surface, through analyzing
      the dynamics of polygonal disks with unilateral point contacts. Similarly to
      earlier works, we determine the rate of energy absorption under the assumption of
      a regular pattern of motion analogous to precession-free motion of a rolling
      disk. In addition, we demonstrate that the asymptotic stability of this motion
      depends on parameters of the impact model. In the case of instability, the
      emerging irregular motion is investigated numerically. We conclude that there
      exists a range of model parameters (small radii of gyration or small restitution
      coefficients) in which absorption by impacts dominates all previously
      investigated mechanisms during the last phase of motion. Nevertheless the
      parameter values associated with a homogeneous disk on a hard surface are
      typically not in this range, hence the effect of impacts is in that case not
      dominant.

PMID- 29347015
TI  - Mathematical and information-geometrical entropy for phenomenological Fourier and
      non-Fourier heat conduction.
AB  - The second law of thermodynamics governs the direction of heat transport, which
      provides the foundational definition of thermodynamic Clausius entropy. The
      definitions of entropy are further generalized for the phenomenological heat
      transport models in the frameworks of classical irreversible thermodynamics and
      extended irreversible thermodynamics (EIT). In this work, entropic functions from
      mathematics are combined with phenomenological heat conduction models and
      connected to several information-geometrical conceptions. The long-time behaviors
      of these mathematical entropies exhibit a wide diversity and physical pictures in
      phenomenological heat conductions, including the tendency to thermal equilibrium,
      and exponential decay of nonequilibrium and asymptotics, which build a bridge
      between the macroscopic and microscopic modelings. In contrast with the EIT
      entropies, the mathematical entropies expressed in terms of the internal energy
      function can avoid singularity paired with nonpositive local absolute temperature
      caused by non-Fourier heat conduction models.

PMID- 29347016
TI  - Modeling a photoinduced planar-to-homeotropic anchoring transition triggered by
      surface azobenzene units in a nematic liquid crystal.
AB  - The performance of light-controlled liquid crystal anchoring surfaces depends on
      the nature of the photosensitive moieties and on the concentration of spacer
      units. Here, we study the kinetics of photosensitive liquid crystal cells that
      incorporate an azobenzene-based self-assembled monolayer. We characterize the
      photoinduced homeotropic-to-planar transition and the subsequent reverse
      relaxation in terms of the underlying isomerization of the photosensitive layer.
      We show that the response time can be precisely adjusted by tuning the lateral
      packing of azobenzene units by means of inert spacer molecules. Using simple
      kinetic assumptions and a well-known model for the energetics of liquid crystal
      anchoring we are able to capture the details of the optical microscopy
      experimental observations. Our analysis provides fitted values for all the
      relevant material parameters, including the zenithal and the azimuthal anchoring
      strength.

PMID- 29347017
TI  - Friction force regimes and the conditions for endless penetration of an intruder
      into a granular medium.
AB  - An intruder penetrating into a granular column experiences a depth-dependent
      friction force F(z). Different regimes of F(z) have been measured depending on
      the experimental design: a nearly linear dependence for shallow penetrations,
      total saturation at large depths, and an exponential increase when the intruder
      approaches the bottom of the granular bed. We report here an experiment that
      allows us to measure the different regimes in a single run during the quasistatic
      descent of a sphere in a light granular medium. From the analysis of the
      resistance in the saturation zone, it was found that F(z) follows a cube-power
      law dependence on the intruder diameter and an exponential increase with the
      packing fraction of the bed. Moreover, we determine the critical mass m_{c}
      required to observe infinite penetration and its dependence on the above
      parameters. Finally, we use our results to estimate the final penetration depth
      reached by intruders of masses m<m_{c}. The results indicate that an intruder of
      any density (larger than the density of the granular bed) can sink indefinitely
      into the granular medium if the bed packing fraction is smaller than a critical
      value.

PMID- 29347018
TI  - Numerical study of enhanced mixing in pressure-driven flows in microchannels
      using a spatially periodic electric field.
AB  - We propose an innovative mechanism for enhancing mixing in steady pressure driven
      flow of an electrolytic solution in a straight rectangular microchannel. A
      transverse electric field is used to generate an electroosmotic flow across the
      cross-section. The resulting flow field consists of a pair of helical vortices
      that transport fluid elements along the channel. We show, through numerical
      simulations, that chaotic advection may be induced by periodically varying the
      direction of the applied electric field along the channel length. This periodic
      electric field generates a longitudinally varying, three-dimensional steady flow,
      such that the streamlines in the first half of the repeating unit cell intersect
      those in the second half, when projected onto the cross-section. Mixing is
      qualitatively characterized by tracking passive particles and obtaining Poincare
      maps. For quantification of the extent of mixing, Shannon entropy is calculated
      using particle advection of a binary mixture. The convection diffusion equation
      is also used to track the evolution of a scalar species and quantify the mixing
      efficiency as a function of the Peclet number.

PMID- 29347019
TI  - Humidity-insensitive water evaporation from molecular complex fluids.
AB  - We investigated theoretically water evaporation from concentrated supramolecular
      mixtures, such as solutions of polymers or amphiphilic molecules, using numerical
      resolutions of a one-dimensional model based on mass transport equations. Solvent
      evaporation leads to the formation of a concentrated solute layer at the drying
      interface, which slows down evaporation in a long-time-scale regime. In this
      regime, often referred to as the falling rate period, evaporation is dominated by
      diffusive mass transport within the solution, as already known. However, we
      demonstrate that, in this regime, the rate of evaporation does not also depend on
      the ambient humidity for many molecular complex fluids. Using analytical
      solutions in some limiting cases, we first demonstrate that a sharp decrease of
      the water chemical activity at high solute concentration leads to evaporation
      rates which depend weakly on the humidity, as the solute concentration at the
      drying interface slightly depends on the humidity. However, we also show that a
      strong decrease of the mutual diffusion coefficient of the solution enhances
      considerably this effect, leading to nearly independent evaporation rates over a
      wide range of humidity. The decrease of the mutual diffusion coefficient indeed
      induces strong concentration gradients at the drying interface, which shield the
      concentration profiles from humidity variations, except in a very thin region
      close to the drying interface.

PMID- 29347020
TI  - Macroscopic violation of the law of heat conduction.
AB  - We analyze a model describing an anharmonic macroscopic chain in contact with
      general reservoirs that follow the Levy-Ito theorem on the Gaussian-Poissonian
      decomposition of the measure. We do so by considering a perturbative approach to
      compute the heat flux and the (canonical) temperature profile when the system
      reaches the steady state. This approach allows observing a macroscopic violation
      of the law of the heat conduction equivalent to that found for small (N=2)
      systems in contact with general reservoirs, which conveys the ascendency of the
      nature of the reservoirs over the size of the system.

PMID- 29347021
TI  - Gaps between avalanches in one-dimensional random-field Ising models.
AB  - We analyze the statistics of gaps (DeltaH) between successive avalanches in one
      dimensional random-field Ising models (RFIMs) in an external field H at zero
      temperature. In the first part of the paper we study the nearest-neighbor
      ferromagnetic RFIM. We map the sequence of avalanches in this system to a
      nonhomogeneous Poisson process with an H-dependent rate rho(H). We use this to
      analytically compute the distribution of gaps P(DeltaH) between avalanches as the
      field is increased monotonically from -infinity to +infinity. We show that
      P(DeltaH) tends to a constant C(R) as DeltaH->0^{+}, which displays a nontrivial
      behavior with the strength of disorder R. We verify our predictions with
      numerical simulations. In the second part of the paper, motivated by avalanche
      gap distributions in driven disordered amorphous solids, we study a long-range
      antiferromagnetic RFIM. This model displays a gapped behavior P(DeltaH)=0 up to a
      system size dependent offset value DeltaH_{off}, and P(DeltaH)~(DeltaH
      DeltaH_{off})^{theta} as DeltaH->H_{off}^{+}. We perform numerical simulations on
      this model and determine theta~0.95(5). We also discuss mechanisms which would
      lead to a nonzero exponent theta for general spin models with quenched random
      fields.

PMID- 29347022
TI  - Destabilization of a liquid metal by nonuniform Joule heating.
AB  - We study the effect of an impressing AC magnetic field at the bottom of a liquid
      metal layer of thickness h. In this situation the fluid is set in motion by the
      buoyancy forces caused by internal heat sources. The heat sources, caused by the
      Joule effect induced by the AC field, present an exponentially decaying profile,
      with characteristic length delta. As the magnetic field is horizontal, the
      Lorentz force has no influence on the dynamics of the system since it contributes
      only to the magnetic pressure. We propose an analysis of both the transient and
      fully developed regimes using linear stability analysis (LSA) and direct
      numerical simulations (DNSs). The transient period is governed by the temporal
      evolution of the temperature field as well as the development of the convective
      instability, which can be concomitant and therefore requires adopting a transient
      LSA algorithm to track these two effects. The DNSs have been performed for
      various distributions of the heat sources and various total heat input. This
      corresponds to independently varying delta/h in the range 0.04<=delta/h<=0.45 and
      a Rayleigh number 1.1*10^{4}<=Ra<=1.2*10^{5}. We observe the relaxation of the
      temperature up to the steady conductive profile before the transition to the
      nonlinear regime when Ra is small, whereas for larger Ra, nonlinear effects
      appear during the relaxation of the temperature profile. The unsteadiness of the
      temperature field significantly alters the development of the instability because
      of a much smaller growth rate. Surprisingly, we observe that delta/h has only a
      limited influence on averaged quantities as well as on the patterns for both the
      linear and nonlinear regimes. This comes with the fact that the profiles present
      an apparent reflectional symmetry, despite the asymmetry of the governing
      equations.

PMID- 29347023
TI  - Stability of the quantum Sherrington-Kirkpatrick spin glass model.
AB  - I study in detail the quantum Sherrington-Kirkpatrick (SK) model, i.e., the
      infinite-range Ising spin glass in a transverse field, by solving numerically the
      effective one-dimensional model that the quantum SK model can be mapped to in the
      thermodynamic limit. I find that the replica symmetric solution is unstable down
      to zero temperature, in contrast to some previous claims, and so there is not
      only a line of transitions in the (longitudinal) field-temperature plane (the de
      Almeida-Thouless, AT, line) where replica symmetry is broken, but also a quantum
      de Almeida-Thouless (QuAT) line in the transverse field-longitudinal field plane
      at T=0. If the QuAT line also occurs in models with short-range interactions its
      presence might affect the performance of quantum annealers when solving spin
      glass-type problems with a bias (i.e., magnetic field).

PMID- 29347024
TI  - Dimensionless embedding for nonlinear time series analysis.
AB  - Recently, infinite-dimensional delay coordinates (InDDeCs) have been proposed for
      predicting high-dimensional dynamics instead of conventional delay coordinates.
      Although InDDeCs can realize faster computation and more accurate short-term
      prediction, it is still not well-known whether InDDeCs can be used in other
      applications of nonlinear time series analysis in which reconstruction is needed
      for the underlying dynamics from a scalar time series generated from a dynamical
      system. Here, we give theoretical support for justifying the use of InDDeCs and
      provide numerical examples to show that InDDeCs can be used for various
      applications for obtaining the recurrence plots, correlation dimensions, and
      maximal Lyapunov exponents, as well as testing directional couplings and
      extracting slow-driving forces. We demonstrate performance of the InDDeCs using
      the weather data. Thus, InDDeCs can eventually realize "dimensionless embedding"
      while we enjoy faster and more reliable computations.

PMID- 29347025
TI  - Distribution of shortest path lengths in a class of node duplication network
      models.
AB  - We present analytical results for the distribution of shortest path lengths
      (DSPL) in a network growth model which evolves by node duplication (ND). The
      model captures essential properties of the structure and growth dynamics of
      social networks, acquaintance networks, and scientific citation networks, where
      duplication mechanisms play a major role. Starting from an initial seed network,
      at each time step a random node, referred to as a mother node, is selected for
      duplication. Its daughter node is added to the network, forming a link to the
      mother node, and with probability p to each one of its neighbors. The degree
      distribution of the resulting network turns out to follow a power-law
      distribution, thus the ND network is a scale-free network. To calculate the DSPL
      we derive a master equation for the time evolution of the probability P_{t}(L=l),
      l=1,2,?, where L is the distance between a pair of nodes and t is the time.
      Finding an exact analytical solution of the master equation, we obtain a closed
      form expression for P_{t}(L=l). The mean distance <L>_{t} and the diameter
      Delta_{t} are found to scale like lnt, namely, the ND network is a small-world
      network. The variance of the DSPL is also found to scale like lnt. Interestingly,
      the mean distance and the diameter exhibit properties of a small-world network,
      rather than the ultrasmall-world network behavior observed in other scale-free
      networks, in which <L>_{t}~lnlnt.

PMID- 29347026
TI  - Analytical theory of the hydrophobic effect of solutes in water.
AB  - We develop an analytical statistical-mechanical model for hydrophobic solvation
      in water. In this three-dimensional Mercedes-Benz-like model, two neighboring
      waters have three possible interaction states: a radial van der Waals
      interaction, a tetrahedral orientation-dependent hydrogen-bonding interaction, or
      no interaction. Nonpolar solutes are modeled as van der Waals particles of
      different radii. The model is sufficiently simple that we can calculate the
      partition function and thermal and volumetric properties of solvation versus
      temperature, pressure, and solute radius. Predictions are in good agreement with
      results of Monte Carlo simulations. And their trends agree with experiments on
      hydrophobic solute insertion. The theory shows that first-shell waters are more
      highly structured than bulk waters, because of hydrogen bonding, and that that
      structure melts out faster with temperature than it does in bulk waters. Because
      the theory is analytical, it can explore a broad range of solvation properties
      and anomalies of water, at minimal computational expense.

PMID- 29347027
TI  - Thermal gas rectification using a sawtooth channel.
AB  - We study the rectification of a two-dimensional thermal gas in a channel of
      asymmetric dissipative walls. For an ensemble of smooth Lennard-Jones particles,
      our numerical simulations reveal a nonmonotonic dependence of the flux on the
      thermostat temperature, channel asymmetry, and particle density, with three
      distinct regimes. Theoretical arguments are developed to shed light on the
      functional dependence of the flux on the model parameters.

PMID- 29347028
TI  - Continuous-time random-walk model for anomalous diffusion in expanding media.
AB  - Expanding media are typical in many different fields, e.g., in biology and
      cosmology. In general, a medium expansion (contraction) brings about dramatic
      changes in the behavior of diffusive transport properties such as the set of
      positional moments and the Green's function. Here, we focus on the
      characterization of such effects when the diffusion process is described by the
      continuous-time random-walk (CTRW) model. As is well known, when the medium is
      static this model yields anomalous diffusion for a proper choice of the
      probability density function (pdf) for the jump length and the waiting time, but
      the behavior may change drastically if a medium expansion is superimposed on the
      intrinsic random motion of the diffusing particle. For the case where the jump
      length and the waiting time pdfs are long-tailed, we derive a general
      bifractional diffusion equation which reduces to a normal diffusion equation in
      the appropriate limit. We then study some particular cases of interest, including
      Levy flights and subdiffusive CTRWs. In the former case, we find an analytical
      exact solution for the Green's function (propagator). When the expansion is
      sufficiently fast, the contribution of the diffusive transport becomes irrelevant
      at long times and the propagator tends to a stationary profile in the comoving
      reference frame. In contrast, for a contracting medium a competition between the
      spreading effect of diffusion and the concentrating effect of contraction arises.
      In the specific case of a subdiffusive CTRW in an exponentially contracting
      medium, the latter effect prevails for sufficiently long times, and all the
      particles are eventually localized at a single point in physical space. This "big
      crunch" effect, totally absent in the case of normal diffusion, stems from
      inefficient particle spreading due to subdiffusion. We also derive a hierarchy of
      differential equations for the moments of the transport process described by the
      subdiffusive CTRW model in an expanding medium. From this hierarchy, the full
      time evolution of the second-order moment is obtained for some specific types of
      expansion. In the case of an exponential expansion, exact recurrence relations
      for the Laplace-transformed moments are obtained, whence the long-time behavior
      of moments of arbitrary order is subsequently inferred. Our analytical and
      numerical results for both Levy flights and subdiffusive CTRWs confirm the
      intuitive expectation that the medium expansion hinders the mixing of diffusive
      particles occupying separate regions. In the case of Levy flights, we quantify
      this effect by means of the so-called "Levy horizon."

PMID- 29347029
TI  - Transient chaos and associated system-intrinsic switching of spacetime patterns
      in two synaptically coupled layers of Morris-Lecar neurons.
AB  - Spatiotemporal chaos collapses to either a rest state or a propagating pulse
      solution in a single layer of diffusively coupled, excitable Morris-Lecar
      neurons. Weak synaptic coupling of two such layers reveals system intrinsic
      switching of spatiotemporal activity patterns within and between the layers at
      irregular times. Within a layer, switching sequences include spatiotemporal
      chaos, erratic and regular pulse propagation, spontaneous network wide neuron
      activity, and rest state. A momentary substantial reduction in neuron activity in
      one layer can reinitiate transient spatiotemporal chaos in the other layer, which
      can induce a swap of spatiotemporal chaos with a pulse state between the layers.
      Presynaptic input maximizes the distance between propagating pulses, in contrast
      to pulse merging in the absence of synapses.

PMID- 29347030
TI  - Phase diagrams for sticky rods in bulk and in a monolayer from a lattice free
      energy functional for anisotropic particles with depletion attractions.
AB  - A density functional of fundamental measure type for a lattice model of
      anisotropic particles with hard-core repulsions and effective attractions is
      derived in the spirit of the Asakura-Oosawa model. Through polymeric lattice
      particles of various size and shape, effective attractions of different strength
      and range between the colloids can be generated. The functional is applied to the
      determination of phase diagrams for sticky rods of length L in two dimensions, in
      three dimensions, and in a monolayer system on a neutral substrate. In all cases,
      there is a competition between ordering and gas-liquid transitions. In two
      dimensions, this gives rise to a tricritical point, whereas in three dimensions,
      the isotropic-nematic transition crosses over smoothly to a gas-nematic liquid
      transition. The richest phase behavior is found for the monolayer system. For
      L=2, two stable critical points are found corresponding to a standard gas-liquid
      transition and a nematic liquid-liquid transition. For L=3, the gas-liquid
      transition becomes metastable.

PMID- 29347031
TI  - Fractality in nonequilibrium steady states of quasiperiodic systems.
AB  - We investigate the nonequilibrium response of quasiperiodic systems to boundary
      driving. In particular, we focus on the Aubry-Andre-Harper model at its metal
      insulator transition and the diagonal Fibonacci model. We find that opening the
      system at the boundaries provides a viable experimental technique to probe its
      underlying fractality, which is reflected in the fractal spatial dependence of
      simple observables (such as magnetization) in the nonequilibrium steady state. We
      also find that the dynamics in the nonequilibrium steady state depends on the
      length of the chain chosen: generic length chains harbour qualitatively slower
      transport (different scaling exponent) than Fibonacci length chains, which is in
      turn slower than in the closed system. We conjecture that such fractal
      nonequilibrium steady states should arise in generic driven critical systems that
      have fractal properties.

PMID- 29347032
TI  - Subspace dynamic mode decomposition for stochastic Koopman analysis.
AB  - The analysis of nonlinear dynamical systems based on the Koopman operator is
      attracting attention in various applications. Dynamic mode decomposition (DMD) is
      a data-driven algorithm for Koopman spectral analysis, and several variants with
      a wide range of applications have been proposed. However, popular implementations
      of DMD suffer from observation noise on random dynamical systems and generate
      inaccurate estimation of the spectra of the stochastic Koopman operator. In this
      paper, we propose subspace DMD as an algorithm for the Koopman analysis of random
      dynamical systems with observation noise. Subspace DMD first computes the
      orthogonal projection of future snapshots to the space of past snapshots and then
      estimates the spectra of a linear model, and its output converges to the spectra
      of the stochastic Koopman operator under standard assumptions. We investigate the
      empirical performance of subspace DMD with several dynamical systems and show its
      utility for the Koopman analysis of random dynamical systems.

PMID- 29347033
TI  - Basins of attraction of the bistable region of time-delayed cutting dynamics.
AB  - This paper investigates the effects of bistability in a nonsmooth time-delayed
      dynamical system, which is often manifested in science and engineering. Previous
      studies on cutting dynamics have demonstrated persistent coexistence of chatter
      and chatter-free responses in a bistable region located in the linearly stable
      zone. As there is no widely accepted definition of basins of attraction for time
      delayed systems, bistable regions are coined as unsafe zones (UZs). Hence, we
      have attempted to define the basins of attraction and stability basins for a
      typical delayed system to get insight into the bistability in systems with time
      delays. Special attention was paid to the influences of delayed initial
      conditions, starting points, and states at time zero on the long-term dynamics of
      time-delayed systems. By using this concept, it has been confirmed that the
      chatter is prone to occur when the waviness frequency in the workpiece surface
      coincides with the effective natural frequency of the cutting process. Further
      investigations unveil a thin "boundary layer" inside the UZ in the immediate
      vicinity of the stability boundary, in which we observe an extremely fast growth
      of the chatter basin stability. The results reveal that the system is more stable
      when the initial cutting depth is smaller. The physics of the tool deflection at
      the instant of the tool-workpiece engagement is used to evaluate the cutting
      safety, and the safe level could be zero when the geometry of tool engagement is
      unfavorable. Finally, the basins of attraction are used to quench the chatter by
      a single strike, where the resultant "islands" offer an opportunity to suppress
      the chatter even when the cutting is very close to the stability boundary.

PMID- 29347034
TI  - Power-law citation distributions are not scale-free.
AB  - We analyze time evolution of statistical distributions of citations to scientific
      papers published in the same year. While these distributions seem to follow the
      power-law dependence we find that they are nonstationary and the exponent of the
      power-law fit decreases with time and does not come to saturation. We attribute
      the nonstationarity of citation distributions to different longevity of the low
      cited and highly cited papers. By measuring citation trajectories of papers we
      found that citation careers of the low-cited papers come to saturation after 10
      15 years while those of the highly cited papers continue to increase
      indefinitely: The papers that exceed some citation threshold become runaways.
      Thus, we show that although citation distribution can look as a power-law
      dependence, it is not scale free and there is a hidden dynamic scale associated
      with the onset of runaways. We compare our measurements to our recently developed
      model of citation dynamics based on copying-redirection-triadic closure and find
      explanations to our empirical observations.

PMID- 29347035
TI  - Aging transition in systems of oscillators with global distributed-delay
      coupling.
AB  - We consider a globally coupled network of active (oscillatory) and inactive
      (nonoscillatory) oscillators with distributed-delay coupling. Conditions for
      aging transition, associated with suppression of oscillations, are derived for
      uniform and gamma delay distributions in terms of coupling parameters and the
      proportion of inactive oscillators. The results suggest that for the uniform
      distribution increasing the width of distribution for the same mean delay allows
      aging transition to happen for a smaller coupling strength and a smaller
      proportion of inactive elements. For gamma distribution with sufficiently large
      mean time delay, it may be possible to achieve aging transition for an arbitrary
      proportion of inactive oscillators, as long as the coupling strength lies in a
      certain range.

PMID- 29347036
TI  - Front propagation in weakly subcritical pattern-forming systems.
AB  - The speed and stability of fronts near a weakly subcritical steady-state
      bifurcation are studied, focusing on the transition between pushed and pulled
      fronts in the bistable Ginzburg-Landau equation. Exact nonlinear front solutions
      are constructed and their stability properties investigated. In some cases, the
      exact solutions are stable but are not selected from arbitrary small amplitude
      initial conditions. In other cases, the exact solution is unstable to
      modulational instabilities which select a distinct front. Chaotic front dynamics
      may result and is studied using numerical techniques.

PMID- 29347037
TI  - Escape of coupled Brownian particles across a fluctuating barrier.
AB  - The escape of two harmonically coupled Brownian particles across the fluctuating
      barrier of a bistable potential is investigated with correlated additive and
      multiplicative fluctuations. Positive correlations enhance the rate of escape
      across the barrier when the coupling is effective, whereas for weakly coupled
      particles, escape becomes difficult. It is found that the system exhibits the
      phenomenon of resonant activation when the rate of barrier fluctuations is
      comparable to the relaxation time in the bistable potential. Using a decoupling
      ansatz, we derive the Markovian limit of the problem in the steady state, under
      the constraint that the barriers fluctuate on a time scale faster than the
      relative oscillation of the two particles. Adiabatic elimination of the fast
      variable of the dynamical system is discussed in appropriate limits.

PMID- 29347038
TI  - Shock propagation in locally driven granular systems.
AB  - We study shock propagation in a system of initially stationary hard spheres that
      is driven by a continuous injection of particles at the origin. The disturbance
      created by the injection of energy spreads radially outward through collisions
      between particles. Using scaling arguments, we determine the exponent
      characterizing the power-law growth of this disturbance in all dimensions. The
      scaling functions describing the various physical quantities are determined using
      large-scale event-driven simulations in two and three dimensions for both elastic
      and inelastic systems. The results are shown to describe well the data from two
      different experiments on granular systems that are similarly driven.

PMID- 29347039
TI  - Recurrence relations in one-dimensional Ising models.
AB  - The exact finite-size partition function for the nonhomogeneous one-dimensional
      (1D) Ising model is found through an approach using algebra operators.
      Specifically, in this paper we show that the partition function can be computed
      through a trace from a linear second-order recurrence relation with nonconstant
      coefficients in matrix form. A relation between the finite-size partition
      function and the generalized Lucas polynomials is found for the simple
      homogeneous model, thus establishing a recursive formula for the partition
      function. This is an important property and it might indicate the possible
      existence of recurrence relations in higher-dimensional Ising models. Moreover,
      assuming quenched disorder for the interactions within the model, the quenched
      averaged magnetic susceptibility displays a nontrivial behavior due to changes in
      the ferromagnetic concentration probability.

PMID- 29347040
TI  - Electrical autonomous Brownian gyrator.
AB  - We study experimentally and theoretically the steady-state dynamics of a simple
      stochastic electronic system featuring two resistor-capacitor circuits coupled by
      a third capacitor. The resistors are subject to thermal noises at real
      temperatures. The voltage fluctuation across each resistor can be compared to a
      one-dimensional Brownian motion. However, the collective dynamical behavior, when
      the resistors are subject to distinct thermal baths, is identical to that of a
      Brownian gyrator, as first proposed by Filliger and Reimann [Phys. Rev. Lett. 99,
      230602 (2007)PRLTAO0031-900710.1103/PhysRevLett.99.230602]. The average gyrating
      dynamics is originated from the absence of detailed balance due to unequal
      thermal baths. We look into the details of this stochastic gyrating dynamics, its
      dependences on the temperature difference and coupling strength, and the
      mechanism of heat transfer through this simple electronic circuit. Our work
      affirms the general principle and the possibility of a Brownian ratchet working
      near room temperature scale.

PMID- 29347041
TI  - Collision rate coefficient for charged dust grains in the presence of linear
      shear.
AB  - Like and oppositely charged particles or dust grains in linear shear flows are
      often driven to collide with one another by fluid and/or electrostatic forces,
      which can strongly influence particle-size distribution evolution. In gaseous
      media, collisions in shear are further complicated because particle inertia can
      influence differential motion. Expressions for the collision rate coefficient
      have not been developed previously which simultaneously account for the
      influences of linear shear, particle inertia, and electrostatic interactions.
      Here, we determine the collision rate coefficient accounting for the
      aforementioned effects by determining the collision area, i.e., the area of the
      plane perpendicular to the shear flow defining the relative initial locations of
      particles which will collide with one another. Integration of the particle flux
      over this area yields the collision rate. Collision rate calculations are
      parametrized as an enhancement factor, i.e., the ratio of the collision rate
      considering potential interactions and inertia to the traditional collision rate
      considering laminar shear only. For particles of constant surface charge density,
      the enhancement factor is found dependent only on the Stokes number (quantifying
      particle inertia), the electrostatic energy to shear energy ratio, and the ratio
      of colliding particle radii. Enhancement factors are determined for Stokes
      numbers in the 0-10 range and energy ratios up to 5. Calculations show that the
      influences of both electrostatic interactions and inertia are significant; for
      inertialess (St=0) equal-sized and oppositely charged particles, we find that
      even at energy ratios as low as 0.2, enhancement factors are in excess of 2. For
      the same situation but like-charged particles, enhancement factors fall below
      0.5. Increasing the Stokes number acts to mitigate the influence of electrostatic
      potentials for both like and oppositely charged particles; i.e., inertia reduces
      the enhancement factor for oppositely charged particles and increases it for like
      charged particles. Uniquely, at elevated Stokes numbers with attractive
      potentials we find collisionless "pockets" within the collision area, which are
      regions completely bounded by the collision area but within which collisions do
      not occur. Regression equations to results are provided, enabling calculation of
      the enhancement factor as a function of energy ratio and Stokes number. In total,
      this study both leads to insight into the collision dynamics of finite-inertia,
      charged particles in shear flows, and provides a means to simply calculate the
      particle-particle collision rate coefficient.

PMID- 29347042
TI  - Probing the excited-state quantum phase transition through statistics of
      Loschmidt echo and quantum work.
AB  - By analyzing the probability distributions of the Loschmidt echo (LE) and quantum
      work, we examine the nonequilibrium effects of a quantum many-body system, which
      exhibits an excited-state quantum phase transition (ESQPT). We find that
      depending on the value of the controlling parameter the distribution of the LE
      displays different patterns. At the critical point of the ESQPT, both the
      averaged LE and the averaged work show a cusplike shape. Furthermore, by
      employing the finite-size scaling analysis of the averaged work, we obtain the
      critical exponent of the ESQPT. Finally, we show that at the critical point of
      ESQPT the eigenstate is a highly localized state, further highlighting the
      influence of the ESQPT on the properties of the many-body system.

PMID- 29347043
TI  - Scaling laws for the mechanics of loose and cohesive granular materials based on
      Baxter's sticky hard spheres.
AB  - We have conducted discrete element simulations (pfc3d) of very loose, cohesive,
      granular assemblies with initial configurations which are drawn from Baxter's
      sticky hard sphere (SHS) ensemble. The SHS model is employed as a promising
      auxiliary means to independently control the coordination number z_{c} of
      cohesive contacts and particle volume fraction phi of the initial states. We
      focus on discerning the role of z_{c} and phi for the elastic modulus, failure
      strength, and the plastic consolidation line under quasistatic, uniaxial
      compression. We find scaling behavior of the modulus and the strength, which both
      scale with the cohesive contact density nu_{c}=z_{c}phi of the initial state
      according to a power law. In contrast, the behavior of the plastic consolidation
      curve is shown to be independent of the initial conditions. Our results show the
      primary control of the initial contact density on the mechanics of cohesive
      granular materials for small deformations, which can be conveniently, but not
      exclusively explored within the SHS-based assembling procedure.

PMID- 29347044
TI  - Monte Carlo simulations of the XY vectorial Blume-Emery-Griffiths model in
      multilayer films for ^{3}He-^{4}He mixtures.
AB  - The XY vectorial generalization of the Blume-Emery-Griffiths (XY-VBEG) model,
      which is suitable to be applied to the study of ^{3}He-^{4}He mixtures, is
      treated on thin films structure and its thermodynamical properties are analyzed
      as a function of the film thickness. We employ extensive and up-to-date Monte
      Carlo simulations consisting of hybrid algorithms combining lattice-gas moves,
      Metropolis, Wolff, and super-relaxation procedures to overcome the critical
      slowing down and correlations among different spin configurations of the system.
      We also make use of single histogram techniques to get the behavior of the
      thermodynamical quantities close to the corresponding transition temperatures.
      Thin films of the XY-VBEG model present a quite rich phase diagram with
      Berezinskii-Kosterlitz-Thouless (BKT) transitions, BKT endpoints, and isolated
      critical points. As one varies the impurity concentrations along the layers, and
      in the limit of infinite film thickness, there is a coalescence of the BKT
      transition endpoint and the isolated critical point into a single, unique
      tricritical point. In addition, when mimicking the behavior of thin films of
      ^{3}He-^{4}He mixtures, one obtains that the concentration of ^{3}He atoms
      decreases from the outer layers to the inner layers of the film, meaning that the
      superfluid particles tend to locate in the bulk of the system.

PMID- 29347045
TI  - Effect of disorder on shrinkage-induced fragmentation of a thin brittle layer.
AB  - We investigate the effect of the amount of disorder on the shrinkage-induced
      cracking of a thin brittle layer attached to a substrate. Based on a discrete
      element model we study how the dynamics of cracking and the size of fragments
      evolve when the amount of disorder is varied. In the model a thin layer is
      discretized on a random lattice of Voronoi polygons attached to a substrate. Two
      sources of disorder are considered: structural disorder captured by the local
      variation of the stiffness and strength disorder represented by the random
      strength of cohesive elements between polygons. Increasing the amount of strength
      disorder, our calculations reveal a transition from a cellular crack pattern,
      generated by the sequential branching and merging of cracks, to a disordered
      ensemble of cracks where the merging of randomly nucleated microcracks dominate.
      In the limit of low disorder, the statistics of fragment size is described by a
      log-normal distribution; however, in the limit of high disorder, a power-law
      distribution is obtained.

PMID- 29347047
TI  - Interface tension in the improved Blume-Capel model.
AB  - We study interfaces with periodic boundary conditions in the low-temperature
      phase of the improved Blume-Capel model on the simple cubic lattice. The
      interface free energy is defined by the difference of the free energy of a system
      with antiperiodic boundary conditions in one of the directions and that of a
      system with periodic boundary conditions in all directions. It is obtained by
      integration of differences of the corresponding internal energies over the
      inverse temperature. These differences can be computed efficiently by using a
      variance reduced estimator that is based on the exchange cluster algorithm. The
      interface tension is obtained from the interface free energy by using predictions
      based on effective interface models. By using our numerical results for the
      interface tension sigma and the correlation length xi obtained in previous work,
      we determine the universal amplitude ratios
      R_{2nd,+}=sigma_{0}f_{2nd,+}^{2}=0.3863(6), R_{2nd,-}=sigma_{0}f_{2nd,
      }^{2}=0.1028(1), and R_{exp,-}=sigma_{0}f_{exp,-}^{2}=0.1077(3). Our results are
      consistent with those obtained previously for the three-dimensional Ising model,
      confirming the universality hypothesis.

PMID- 29347046
TI  - Cortical geometry as a determinant of brain activity eigenmodes: Neural field
      analysis.
AB  - Perturbation analysis of neural field theory is used to derive eigenmodes of
      neural activity on a cortical hemisphere, which have previously been calculated
      numerically and found to be close analogs of spherical harmonics, despite heavy
      cortical folding. The present perturbation method treats cortical folding as a
      first-order perturbation from a spherical geometry. The first nine spatial
      eigenmodes on a population-averaged cortical hemisphere are derived and compared
      with previous numerical solutions. These eigenmodes contribute most to brain
      activity patterns such as those seen in electroencephalography and functional
      magnetic resonance imaging. The eigenvalues of these eigenmodes are found to
      agree with the previous numerical solutions to within their uncertainties. Also
      in agreement with the previous numerics, all eigenmodes are found to closely
      resemble spherical harmonics. The first seven eigenmodes exhibit a one-to-one
      correspondence with their numerical counterparts, with overlaps that are close to
      unity. The next two eigenmodes overlap the corresponding pair of numerical
      eigenmodes, having been rotated within the subspace spanned by that pair, likely
      due to second-order effects. The spatial orientations of the eigenmodes are found
      to be fixed by gross cortical shape rather than finer-scale cortical properties,
      which is consistent with the observed intersubject consistency of functional
      connectivity patterns. However, the eigenvalues depend more sensitively on finer
      scale cortical structure, implying that the eigenfrequencies and consequent
      dynamical properties of functional connectivity depend more strongly on details
      of individual cortical folding. Overall, these results imply that well
      established tools from perturbation theory and spherical harmonic analysis can be
      used to calculate the main properties and dynamics of low-order brain eigenmodes.

PMID- 29347048
TI  - Distribution of randomly diffusing particles in inhomogeneous media.
AB  - Diffusion can be conceptualized, at microscopic scales, as the random hopping of
      particles between neighboring lattice sites. In the case of diffusion in
      inhomogeneous media, distinct spatial domains in the system may yield distinct
      particle hopping rates. Starting from the master equations (MEs) governing
      diffusion in inhomogeneous media we derive here, for arbitrary spatial
      dimensions, the deterministic lattice equations (DLEs) specifying the average
      particle number at each lattice site for randomly diffusing particles in
      inhomogeneous media. We consider the case of free (Fickian) diffusion with no
      steric constraints on the maximum particle number per lattice site as well as the
      case of diffusion under steric constraints imposing a maximum particle
      concentration. We find, for both transient and asymptotic regimes, excellent
      agreement between the DLEs and kinetic Monte Carlo simulations of the MEs. The
      DLEs provide a computationally efficient method for predicting the (average)
      distribution of randomly diffusing particles in inhomogeneous media, with the
      number of DLEs associated with a given system being independent of the number of
      particles in the system. From the DLEs we obtain general analytic expressions for
      the steady-state particle distributions for free diffusion and, in special cases,
      diffusion under steric constraints in inhomogeneous media. We find that, in the
      steady state of the system, the average fraction of particles in a given domain
      is independent of most system properties, such as the arrangement and shape of
      domains, and only depends on the number of lattice sites in each domain, the
      particle hopping rates, the number of distinct particle species in the system,
      and the total number of particles of each particle species in the system. Our
      results provide general insights into the role of spatially inhomogeneous
      particle hopping rates in setting the particle distributions in inhomogeneous
      media.

PMID- 29347049
TI  - Deviation from fluctuation-dissipation relation for driven superdiffusion:
      Polymer stretching as an example.
AB  - We discuss a deviation of the fluctuation-dissipation relation (FDR) in a driven
      superdiffusive system as exemplified by polymer stretching. The superdiffusion is
      found by monitoring momentum transfer to a tracer, which is a conjugate
      observable with the position. Molecular-dynamics simulation demonstrates that the
      FDR deviates during the nonequilibrium transient process. We then propose
      nonequilibrium mode analysis for superdiffusion, which is a counterpart to that
      for driven subdiffusion. The mode analysis yields results that are in qualitative
      agreement with the simulation results, suggesting that the fluctuations of the
      stiffness in the system from initial equilibrium to stretching account for the
      FDR deviation.

PMID- 29347050
TI  - Manipulation of double-stranded DNA melting by force.
AB  - By integrating elasticity-as described by the Gaussian network model-with bond
      binding energies that distinguish between different base-pair identities and
      stacking configurations, we study the force induced melting of a double-stranded
      DNA (dsDNA). Our approach is a generalization of our previous study of thermal
      dsDNA denaturation [J. Chem. Phys. 145, 144101 (2016)JCPSA60021
      960610.1063/1.4964285] to that induced by force at finite temperatures. It allows
      us to obtain semimicroscopic information about the opening of the chain, such as
      whether the dsDNA opens from one of the ends or from the interior, forming an
      internal bubble. We study different types of force manipulation: (i) "end
      unzipping," with force acting at a single end base pair perpendicular to the
      helix, (ii) "midunzipping," with force acting at a middle base pair perpendicular
      to the helix, and (iii) "end shearing," where the force acts at opposite ends
      along the helix. By monitoring the free-energy landscape and probability
      distribution of intermediate denaturation states, we show that different dominant
      intermediate states are stabilized depending on the type of force manipulation
      used. In particular, the bubble state of the sequence L60B36, which we have
      previously found to be a stable state during thermal denaturation, is absent for
      end unzipping and end shearing, whereas very similar bubbles are stabilized by
      midunzipping, or when the force location is near the middle of the chain. Ours
      results offer a simple tool for stabilizing bubbles and loops using force
      manipulations at different temperatures, and may implicate on the mechanism in
      which DNA enzymes or motors open regions of the chain.

PMID- 29347051
TI  - Enhanced capital-asset pricing model for the reconstruction of bipartite
      financial networks.
AB  - Reconstructing patterns of interconnections from partial information is one of
      the most important issues in the statistical physics of complex networks. A
      paramount example is provided by financial networks. In fact, the spreading and
      amplification of financial distress in capital markets are strongly affected by
      the interconnections among financial institutions. Yet, while the aggregate
      balance sheets of institutions are publicly disclosed, information on single
      positions is mostly confidential and, as such, unavailable. Standard approaches
      to reconstruct the network of financial interconnection produce unrealistically
      dense topologies, leading to a biased estimation of systemic risk. Moreover,
      reconstruction techniques are generally designed for monopartite networks of
      bilateral exposures between financial institutions, thus failing in reproducing
      bipartite networks of security holdings (e.g., investment portfolios). Here we
      propose a reconstruction method based on constrained entropy maximization,
      tailored for bipartite financial networks. Such a procedure enhances the
      traditional capital-asset pricing model (CAPM) and allows us to reproduce the
      correct topology of the network. We test this enhanced CAPM (ECAPM) method on a
      dataset, collected by the European Central Bank, of detailed security holdings of
      European institutional sectors over a period of six years (2009-2015). Our
      approach outperforms the traditional CAPM and the recently proposed maximum
      entropy CAPM both in reproducing the network topology and in estimating systemic
      risk due to fire sales spillovers. In general, ECAPM can be applied to the whole
      class of weighted bipartite networks described by the fitness model.

PMID- 29347052
TI  - Capacitively coupled rf discharge with a large amount of microparticles:
      Spatiotemporal emission pattern and microparticle arrangement.
AB  - The effect of micron-sized particles on a low-pressure capacitively coupled rf
      discharge is studied both experimentally and using numerical simulations. In the
      laboratory experiments, microparticle clouds occupying a considerable fraction of
      the discharge volume are supported against gravity with the help of the
      thermophoretic force. The spatiotemporally resolved optical emission measurements
      are performed with different arrangements of microparticles. The numerical
      simulations are carried out on the basis of a one-dimensional hybrid (fluid
      kinetic) discharge model describing the interaction between plasma and
      microparticles in a self-consistent way. The study is focused on the role of
      microparticle arrangement in interpreting the spatiotemporal emission
      measurements. We show that it is not possible to reproduce simultaneously the
      observed microparticle arrangement and emission pattern in the framework of the
      considered one-dimensional model. This disagreement can be attributed to the two
      dimensional effects (e.g., radial diffusion of the plasma components) or to the
      lack of the proper description of the sharp void boundary in the frame of fluid
      approach.

PMID- 29347053
TI  - Radiation-pressure-driven ion Weibel instability and collisionless shocks.
AB  - The Weibel instability from counterstreaming plasma flows is a basic process
      highly relevant for collisionless shock formation in astrophysics. In this paper
      we investigate, via two- and three-dimensional simulations, suitable
      configurations for laboratory investigations of the ion Weibel instability (IWI)
      driven by a fast quasineutral plasma flow launched into the target via the
      radiation pressure of an ultra-high-intensity laser pulse ("hole-boring"
      process). The use of S-polarized light at oblique incidence is found to be an
      optimal configuration for driving IWI, as it prevents the development of surface
      rippling observed at normal incidence that would lead to strong electron heating
      and would favor competing instabilities. Conditions for the evolution of IWI into
      a collisionless shock are also investigated.

PMID- 29347054
TI  - Chaos-based wireless communication resisting multipath effects.
AB  - In additive white Gaussian noise channel, chaos has been shown to be the optimal
      coherent communication waveform in the sense of using a very simple matched
      filter to maximize the signal-to-noise ratio. Recently, Lyapunov exponent
      spectrum of the chaotic signals after being transmitted through a wireless
      channel has been shown to be unaltered, paving the way for wireless communication
      using chaos. In wireless communication systems, inter-symbol interference caused
      by multipath propagation is one of the main obstacles to achieve high bit
      transmission rate and low bit-error rate (BER). How to resist the multipath
      effect is a fundamental problem in a chaos-based wireless communication system
      (CWCS). In this paper, a CWCS is built to transmit chaotic signals generated by a
      hybrid dynamical system and then to filter the received signals by using the
      corresponding matched filter to decrease the noise effect and to detect the
      binary information. We find that the multipath effect can be effectively resisted
      by regrouping the return map of the received signal and by setting the
      corresponding threshold based on the available information. We show that the
      optimal threshold is a function of the channel parameters and of the information
      symbols. Practically, the channel parameters are time-variant, and the future
      information symbols are unavailable. In this case, a suboptimal threshold is
      proposed, and the BER using the suboptimal threshold is derived analytically.
      Simulation results show that the CWCS achieves a remarkable competitive
      performance even under inaccurate channel parameters.

PMID- 29347055
TI  - Renormalization group theory outperforms other approaches in statistical
      comparison between upscaling techniques for porous media.
AB  - Determining the pressure differential required to achieve a desired flow rate in
      a porous medium requires solving Darcy's law, a Laplace-like equation, with a
      spatially varying tensor permeability. In various scenarios, the permeability
      coefficient is sampled at high spatial resolution, which makes solving Darcy's
      equation numerically prohibitively expensive. As a consequence, much effort has
      gone into creating upscaled or low-resolution effective models of the coefficient
      while ensuring that the estimated flow rate is well reproduced, bringing to the
      fore the classic tradeoff between computational cost and numerical accuracy. Here
      we perform a statistical study to characterize the relative success of upscaling
      methods on a large sample of permeability coefficients that are above the
      percolation threshold. We introduce a technique based on mode-elimination
      renormalization group theory (MG) to build coarse-scale permeability
      coefficients. Comparing the results with coefficients upscaled using other
      methods, we find that MG is consistently more accurate, particularly due to its
      ability to address the tensorial nature of the coefficients. MG places a low
      computational demand, in the manner in which we have implemented it, and accurate
      flow-rate estimates are obtained when using MG-upscaled permeabilities that
      approach or are beyond the percolation threshold.

PMID- 29347056
TI  - Force-linearization closure for non-Markovian Langevin systems with time delay.
AB  - This paper is concerned with the Fokker-Planck (FP) description of classical
      stochastic systems with discrete time delay. The non-Markovian character of the
      corresponding Langevin dynamics naturally leads to a coupled infinite hierarchy
      of FP equations for the various n-time joint distribution functions. Here, we
      present an approach to close the hierarchy at the one-time level based on a
      linearization of the deterministic forces in all members of the hierarchy
      starting from the second one. This leads to a closed equation for the one-time
      probability density in the steady state. Considering two generic nonlinear
      systems, a colloidal particle in a sinusoidal or bistable potential supplemented
      by a linear delay force, we demonstrate that our approach yields a very accurate
      representation of the density as compared to quasiexact numerical results from
      direct solution of the Langevin equation. Moreover, the results are significantly
      improved against those from a small-delay approximation and a perturbation
      theoretical approach. We also discuss the possibility of accessing transport
      related quantities, such as escape times, based on an additional Kramers
      approximation. Our approach applies to a wide class of models with nonlinear
      deterministic forces.

PMID- 29347057
TI  - Revisiting the use of the immersed-boundary lattice-Boltzmann method for
      simulations of suspended particles.
AB  - The immersed-boundary lattice-Boltzmann method (IB-LBM) is increasingly being
      used in simulations of dense suspensions. These systems are computationally very
      expensive and can strongly benefit from lower resolutions that still maintain the
      desired accuracy for the quantities of interest. IB-LBM has a number of free
      parameters that have to be defined, often without exact knowledge of the
      tradeoffs, since their behavior in low resolutions is not well understood. Such
      parameters are the lattice constant Deltax, the number of vertices N_{v}, the
      interpolation kernel phi, and the LBM relaxation time tau. We investigate the
      effect of these IB-LBM parameters on a number of straightforward but challenging
      benchmarks. The systems considered are (a) the flow of a single sphere in shear
      flow, (b) the collision of two spheres in shear flow, and (c) the lubrication
      interaction of two spheres. All benchmarks are performed in three dimensions. The
      first two systems are used for determining two effective radii: the hydrodynamic
      radius r_{hyd} and the particle interaction radius r_{inter}. The last system is
      used to establish the numerical robustness of the lubrication forces, used to
      probe the hydrodynamic interactions in the limit of small gaps. Our results show
      that lower spatial resolutions result in larger hydrodynamic and interaction
      radii, while surface densities should be chosen above two vertices per LU^{2}
      result to prevent fluid penetration in underresolved meshes. Underresolved meshes
      also failed to produce the migration of particles toward the center of the domain
      due to lift forces in Couette flow, mostly noticeable for IBM-kernel phi_{2}.
      Kernel phi_{4}, despite being more robust toward mesh resolution, produces a
      notable membrane thickness, leading to the breakdown of the lubrication forces in
      larger gaps, and its use in dense suspensions where the mean particle distances
      are small can result in undesired behavior. r_{hyd} is measured to be different
      from r_{inter}, suggesting that there is no consistent measure to recalibrate the
      radius of the suspended particle.

PMID- 29347058
TI  - Fluctuations in percolation of sparse complex networks.
AB  - We study the role of fluctuations in percolation of sparse complex networks. To
      this end we consider two random correlated realizations of the initial damage of
      the nodes and we evaluate the fraction of nodes that are expected to remain in
      the giant component of the network in both cases or just in one case. Our
      framework includes a message-passing algorithm able to predict the fluctuations
      in a single network, and an analytic prediction of the expected fluctuations in
      ensembles of sparse networks. This approach is applied to real ecological and
      infrastructure networks and it is shown to characterize the expected fluctuations
      in their response to external damage.

PMID- 29347059
TI  - Acoustic streaming in a microfluidic channel with a reflector: Case of a standing
      wave generated by two counterpropagating leaky surface waves.
AB  - A theory is developed for the modeling of acoustic streaming in a microfluidic
      channel confined between an elastic solid wall and a rigid reflector. A situation
      is studied where the acoustic streaming is produced by two leaky surface waves
      that propagate towards each other in the solid wall and thus form a combined
      standing wave in the fluid. Full analytical solutions are found for both the
      linear acoustic field and the field of the acoustic streaming. A dispersion
      equation is derived that allows one to calculate the wave speed in the system
      under study. The obtained solutions are used to consider particular numerical
      examples and to reveal the structure of the acoustic streaming. It is shown that
      two systems of vortices are established along the boundaries of the microfluidic
      channel.

PMID- 29347060
TI  - Contact angle entropy and macroscopic friction in noncohesive two-dimensional
      granular packings.
AB  - We study the relationship between the granular contact angle distribution and
      local particle friction on the macroscopic friction and bulk modulus in
      noncohesive disk packings. Molecular dynamics in two dimensions are used to
      simulate uniaxial loading-unloading cycles imposed on the granular packings.
      While macroscopic Mohr friction depends on the granular pack geometric details,
      it reaches a stationary limit after a finite number of loading-unloading cycles
      that render well-defined values for bulk modulus, grain coordination, porosity,
      and friction. For random packings and for all polydispersities analyzed, we found
      that as interparticle friction increases, the bulk modulus for the limit cycle
      decreases linearly, while the mean coordination number is reduced and the
      porosity increased, also as approximately linear functions. On the other hand,
      the macroscopic Mohr friction increases in a monotonous trend with interparticle
      friction. The latter result is compared to a theoretical model that assumes the
      existence of sliding planes corresponding to definite Mohr-friction values. The
      simulation results for macroscopic friction are well described by the theoretical
      model that incorporates the local neighbor angle distribution that can be
      quantified through the contact angle entropy. As local friction is increased, the
      limit entropy of the neighbor angle distribution is reduced, thus introducing the
      geometric component to granular friction. Surprisingly, once the limit cycle is
      reached, the Mohr friction seems to be insensitive to polydispersity as has been
      recently reported.

PMID- 29347061
TI  - Predictions of first passage times in sparse discrete fracture networks using
      graph-based reductions.
AB  - We present a graph-based methodology to reduce the computational cost of
      obtaining first passage times through sparse fracture networks. We derive graph
      representations of generic three-dimensional discrete fracture networks (DFNs)
      using the DFN topology and flow boundary conditions. Subgraphs corresponding to
      the union of the k shortest paths between the inflow and outflow boundaries are
      identified and transport on their equivalent subnetworks is compared to transport
      through the full network. The number of paths included in the subgraphs is based
      on the scaling behavior of the number of edges in the graph with the number of
      shortest paths. First passage times through the subnetworks are in good agreement
      with those obtained in the full network, both for individual realizations and in
      distribution. Accurate estimates of first passage times are obtained with an
      order of magnitude reduction of CPU time and mesh size using the proposed method.

PMID- 29347062
TI  - From thermal to excited-state quantum phase transition: The Dicke model.
AB  - We study the thermodynamics of the full version of the Dicke model, including all
      the possible values of the total angular momentum j, with both microcanonical and
      canonical ensembles. We focus on both the excited-state quantum phase transition,
      appearing in the microcanonical description of the maximum angular momentum
      sector, j=N/2, and the thermal phase transition, which occurs when all the
      sectors are taken into account. We show that two different features characterize
      the full version of the Dicke model. If the system is in contact with a thermal
      bath and is described by means of the canonical ensemble, the parity symmetry
      becomes spontaneously broken at the critical temperature. In the microcanonical
      ensemble, and despite that all the logarithmic singularities which characterize
      the excited-state quantum phase transition are ruled out when all the j sectors
      are considered, there still exists a critical energy (or temperature) dividing
      the spectrum into two regions: one in which the parity symmetry can be broken,
      and another in which this symmetry is always well defined.

PMID- 29347063
TI  - Smallest quantum thermal machine: The effect of strong coupling and distributed
      thermal tasks.
AB  - The functions of the smallest self-contained thermal machine consisting of a
      single qutrit are studied when the weak internal coupling assumption is relaxed.
      It is shown that in the presence of one target to be cooled the strong coupling
      is not beneficial to the refrigeration. The reason is explained by examining the
      effect of the strong coupling on the contributions of all eigenstates transitions
      to the heat current of the related thermal reservoir. When acting simultaneously
      on two targets, the machine can be manipulated to implement distributed tasks on
      them, such as cooling one target and meanwhile heating another one, by adjusting
      the coupling strengths between the machine with the two targets. In particular,
      we show that the machine can realize temperature reversal for the two qubits,
      namely, the qubit that is coupled to the high temperature reservoir is
      refrigerated to a temperature below that of the qubit contacting with the low
      temperature reservoir.

PMID- 29347064
TI  - Anisotropic decay of the energy spectrum in two-dimensional dense granular flows.
AB  - We study anisotropic collective motions of two-dimensional granular particles
      under simple shear deformations. Employing molecular-dynamics simulations of
      large system sizes, we find that anisotropic fluidized bands develop in the
      system yielding under quasistatic deformations, where the spectrum of nonaffine
      velocities, which is associated with the energy spectrum for turbulent flows,
      exhibits a quadrupole structure. To explain theoretically the anisotropic
      spectrum, we derive hydrodynamic modes from a continuum model of dense granular
      materials, where we find that fluidized bands are caused by long-lived
      hydrodynamic fluctuations characterized by compressibility.

PMID- 29347065
TI  - Theory of wavelet-based coarse-graining hierarchies for molecular dynamics.
AB  - We present a multiresolution approach to compressing the degrees of freedom and
      potentials associated with molecular dynamics, such as the bond potentials. The
      approach suggests a systematic way to accelerate large-scale molecular
      simulations with more than two levels of coarse graining, particularly
      applications of polymeric materials. In particular, we derive explicit models for
      (arbitrarily large) linear (homo)polymers and iterative methods to compute large
      scale wavelet decompositions from fragment solutions. This approach does not
      require explicit preparation of atomistic-to-coarse-grained mappings, but instead
      uses the theory of diffusion wavelets for graph Laplacians to develop system
      specific mappings. Our methodology leads to a hierarchy of system-specific coarse
      grained degrees of freedom that provides a conceptually clear and mathematically
      rigorous framework for modeling chemical systems at relevant model scales. The
      approach is capable of automatically generating as many coarse-grained model
      scales as necessary, that is, to go beyond the two scales in conventional coarse
      grained strategies; furthermore, the wavelet-based coarse-grained models
      explicitly link time and length scales. Furthermore, a straightforward method for
      the reintroduction of omitted degrees of freedom is presented, which plays a
      major role in maintaining model fidelity in long-time simulations and in
      capturing emergent behaviors.

PMID- 29347066
TI  - Mean-field approach to evolving spatial networks, with an application to
      osteocyte network formation.
AB  - We consider evolving networks in which each node can have various associated
      properties (a state) in addition to those that arise from network structure. For
      example, each node can have a spatial location and a velocity, or it can have
      some more abstract internal property that describes something like a social
      trait. Edges between nodes are created and destroyed, and new nodes enter the
      system. We introduce a "local state degree distribution" (LSDD) as the degree
      distribution at a particular point in state space. We then make a mean-field
      assumption and thereby derive an integro-partial differential equation that is
      satisfied by the LSDD. We perform numerical experiments and find good agreement
      between solutions of the integro-differential equation and the LSDD from
      stochastic simulations of the full model. To illustrate our theory, we apply it
      to a simple model for osteocyte network formation within bones, with a view to
      understanding changes that may take place during cancer. Our results suggest that
      increased rates of differentiation lead to higher densities of osteocytes, but
      with a smaller number of dendrites. To help provide biological context, we also
      include an introduction to osteocytes, the formation of osteocyte networks, and
      the role of osteocytes in bone metastasis.

PMID- 29347067
TI  - Isotropic-nematic transition for hard rods on a three-dimensional cubic lattice.
AB  - Using grand-canonical Monte Carlo (GCMC) simulations, we investigate the
      isotropic-nematic phase transition for hard rods of size L*1*1 on a three
      dimensional cubic lattice. We observe such a transition for L>=6. For L=6, the
      nematic state has a negative order parameter, reflecting the co-occurrence of two
      dominating orientations. For L>=7, the nematic state has a positive order
      parameter, corresponding to the dominance of one orientation. We investigate rod
      lengths up to L=25 and find evidence for a very weakly first-order isotropic
      nematic transition, while we cannot completely rule out a second-order
      transition. It was not possible to detect a density jump at the transition,
      despite using large systems containing several 10^{5} particles. The probability
      density distributions P(Q) from the GCMC simulations near the transition are very
      broad, pointing to strong fluctuations. Our results complement earlier results on
      the demixing (pseudonematic) transition for an equivalent system in two
      dimensions, which is presumably of Ising type and occurs for L>=7. We compare our
      results to lattice fundamental measure theory (FMT) and find that FMT strongly
      overestimates nematic order and consequently predicts a strong first-order
      transition. The rod packing fraction of the nematic coexisting states, however,
      agree reasonably well between FMT and GCMC.

PMID- 29347068
TI  - How to determine a boundary condition for diffusion at a thin membrane from
      experimental data.
AB  - We present a method of deriving a boundary condition for diffusion at a thin
      membrane from experimental data. Based on experimental results obtained for
      normal diffusion of ethanol in water, we show that the derived boundary condition
      at a membrane contains a term with a Riemann-Liouville fractional time derivative
      of order 1/2. Such a form of the boundary condition shows that a transfer of
      particles through a thin membrane is a "long-memory process." The presented
      method is an example that an important part of the mathematical model of physical
      processes may be derived directly from experimental data.

PMID- 29347069
TI  - Adaptive numerical algorithms to simulate the dynamical Casimir effect in a
      closed cavity with different boundary conditions.
AB  - We present an alternative numerical approach to compute the number of particles
      created inside a cavity due to time-dependent boundary conditions. The physical
      model consists of a rectangular cavity, where a wall always remains still while
      the other wall of the cavity presents a smooth movement in one direction. The
      method relies on the setting of the boundary conditions (Dirichlet and Neumann)
      and the following resolution of the corresponding equations of modes. By a
      further comparison between the ground state before and after the movement of the
      cavity wall, we finally compute the number of particles created. To demonstrate
      the method, we investigate the creation of particle production in vibrating
      cavities, confirming previously known results in the appropriate limits. Within
      this approach, the dynamical Casimir effect can be investigated, making it
      possible to study a variety of scenarios where no analytical results are known.
      Of special interest is, of course, the realistic case of the electromagnetic
      field in a three-dimensional cavity, with transverse electric (TE)-mode and
      transverse magnetic (TM)-mode photon production. Furthermore, with our approach
      we are able to calculate numerically the particle creation in a tuneable resonant
      superconducting cavity by the use of the generalized Robin boundary condition. We
      compare the numerical results with analytical predictions as well as a different
      numerical approach. Its extension to three dimensions is also straightforward.

PMID- 29347070
TI  - Instabilities of conducting fluid layers in weak time-dependent magnetic fields.
AB  - We present the experimental analysis of the instabilities generated on a large
      drop of liquid metal by a time-dependent magnetic field. The study is done
      exploring the range of tiny values of the control parameter (the ratio between
      the Lorentz forces and inertia) avoiding nonlinear effects. Two different
      instabilities break the symmetries generating spatial patterns that appear
      without a threshold for some specific frequencies (up to the experimental
      precision) and have been observed for parameter values two orders of magnitude
      lower than in previously published experiments [J. Fluid Mech. 239, 383
      (1992)JFLSA70022-112010.1017/S0022112092004452]. One of the instabilities
      corresponds to a boundary condition oscillation that generates surface waves and
      breaks the azimuthal symmetry. The other corresponds to a parametric forcing
      through a modulation of the Lorentz force. The competition between these two
      mechanisms produces time-dependent patterns near codimension-2 points.

PMID- 29347071
TI  - Consistency of detrended fluctuation analysis.
AB  - The scaling function F(s) in detrended fluctuation analysis (DFA) scales as
      F(s)~s^{H} for stochastic processes with Hurst exponent H. This scaling law is
      proven for stationary stochastic processes with 0<H<1 and nonstationary
      stochastic processes with 1<H<2. For H<0.5, it is observed that the asymptotic
      (power-law) autocorrelation function (ACF) scales as ~s^{1/2}. It is also
      demonstrated that the fluctuation function in DFA is equal in expectation to (i)
      a weighted sum of the ACF and (ii) a weighted sum of the second-order structure
      function. These results enable us to compute the exact finite-size bias for
      signals that are scaling and to employ DFA in a meaningful sense for signals that
      do not exhibit power-law statistics. The usefulness is illustrated by examples
      where it is demonstrated that a previous suggested modified DFA will increase the
      bias for signals with Hurst exponents 1<H<=1.5. As a final application of these
      developments, an estimator F[over ](s) is proposed. This estimator can handle
      missing data in regularly sampled time series without the need of interpolation
      schemes. Under mild regularity conditions, F[over ](s) is equal in expectation to
      the fluctuation function F(s) in the gap-free case.

PMID- 29347072
TI  - Macroscopic and microscopic spectral properties of brain networks during local
      and global synchronization.
AB  - We introduce a practical and computationally not demanding technique for
      inferring interactions at various microscopic levels between the units of a
      network from the measurements and the processing of macroscopic signals. Starting
      from a network model of Kuramoto phase oscillators, which evolve adaptively
      according to homophilic and homeostatic adaptive principles, we give evidence
      that the increase of synchronization within groups of nodes (and the
      corresponding formation of synchronous clusters) causes also the defragmentation
      of the wavelet energy spectrum of the macroscopic signal. Our methodology is then
      applied to getting a glance into the microscopic interactions occurring in a
      neurophysiological system, namely, in the thalamocortical neural network of an
      epileptic brain of a rat, where the group electrical activity is registered by
      means of multichannel EEG. We demonstrate that it is possible to infer the degree
      of interaction between the interconnected regions of the brain during different
      types of brain activities and to estimate the regions' participation in the
      generation of the different levels of consciousness.

PMID- 29347073
TI  - Orientational dynamics of a triaxial ellipsoid in simple shear flow: Influence of
      inertia.
AB  - The motion of a single ellipsoidal particle in simple shear flow can provide
      valuable insights toward understanding suspension flows with nonspherical
      particles. Previously, extensive studies have been performed on the ellipsoidal
      particle with rotational symmetry, a so-called spheroid. The nearly prolate
      ellipsoid (one major and two minor axes of almost equal size) is known to perform
      quasiperiodic or even chaotic orbits in the absence of inertia. With small
      particle inertia, the particle is also known to drift toward this irregular
      motion. However, it is not previously understood what effects from fluid inertia
      could be, which is of highest importance for particles close to neutral buoyancy.
      Here, we find that fluid inertia is acting strongly to suppress the chaotic
      motion and only very weak fluid inertia is sufficient to stabilize a rotation
      around the middle axis. The mechanism responsible for this transition is believed
      to be centrifugal forces acting on fluid, which is dragged along with the
      rotational motion of the particle. With moderate fluid inertia, it is found that
      nearly prolate triaxial particles behave similarly to the perfectly spheroidal
      particles. Finally, we also are able to provide predictions about the stable
      rotational states for the general triaxial ellipsoid in simple shear with weak
      inertia.

PMID- 29347074
TI  - Explosive percolation on directed networks due to monotonic flow of activity.
AB  - An important class of real-world networks has directed edges, and in addition,
      some rank ordering on the nodes, for instance the popularity of users in online
      social networks. Yet, nearly all research related to explosive percolation has
      been restricted to undirected networks. Furthermore, information on such rank
      ordered networks typically flows from higher-ranked to lower-ranked individuals,
      such as follower relations, replies, and retweets on Twitter. Here we introduce a
      simple percolation process on an ordered, directed network where edges are added
      monotonically with respect to the rank ordering. We show with a numerical
      approach that the emergence of a dominant strongly connected component appears to
      be discontinuous. Large-scale connectivity occurs at very high density compared
      with most percolation processes, and this holds not just for the strongly
      connected component structure but for the weakly connected component structure as
      well. We present analysis with branching processes, which explains this unusual
      behavior and gives basic intuition for the underlying mechanisms. We also show
      that before the emergence of a dominant strongly connected component, multiple
      giant strongly connected components may exist simultaneously. By adding a
      competitive percolation rule with a small bias to link uses of similar rank, we
      show this leads to formation of two distinct components, one of high-ranked
      users, and one of low-ranked users, with little flow between the two components.

PMID- 29347075
TI  - Rogue wave solutions for the infinite integrable nonlinear Schrodinger equation
      hierarchy.
AB  - We present rogue wave solutions of the integrable nonlinear Schrodinger equation
      hierarchy with an infinite number of higher-order terms. The latter include
      higher-order dispersion and higher-order nonlinear terms. In particular, we
      derive the fundamental rogue wave solutions for all orders of the hierarchy, with
      exact expressions for velocities, phase, and "stretching factors" in the
      solutions. We also present several examples of exact solutions of second-order
      rogue waves, including rogue wave triplets.

PMID- 29347076
TI  - Optimizing stability of mutual synchronization between a pair of limit-cycle
      oscillators with weak cross coupling.
AB  - We consider optimization of the linear stability of synchronized states between a
      pair of weakly coupled limit-cycle oscillators with cross coupling, where
      different components of state variables of the oscillators are allowed to
      interact. On the basis of the phase reduction theory, we derive the coupling
      matrix between different components of the oscillator states that maximizes the
      linear stability of the synchronized state under given constraints on the overall
      coupling intensity and the stationary phase difference. The improvement in the
      linear stability is illustrated by using several types of limit-cycle oscillators
      as examples.

PMID- 29347077
TI  - Entropy production for complex Langevin equations.
AB  - We study irreversible processes for nonlinear oscillators networks described by
      complex-valued Langevin equations that account for coupling to different
      thermochemical baths. Dissipation is introduced via non-Hermitian terms in the
      Hamiltonian of the model. We apply the stochastic thermodynamics formalism to
      compute explicit expressions for the entropy production rates. We discuss in
      particular the nonequilibrium steady states of the network characterized by a
      constant production rate of entropy and flows of energy and particle currents.
      For two specific examples, a one-dimensional chain and a dimer, numerical
      calculations are presented. The role of asymmetric coupling among the oscillators
      on the entropy production is illustrated.

PMID- 29347078
TI  - Collisional heating and adiabatic expansion of warm dense matter with intense
      relativistic electrons.
AB  - Adiabatic expansion of a warm dense Ti plasma has been observed after isochoric
      heating of a 100-MUm-thick Ti foil with an ~100-ns-long intense relativistic
      electron bunch at an energy of 19.8 MeV and a current of 1.7 kA. The expansion
      fits well with the analytical point-source solution. After 10 J is deposited and
      the plasma rapidly expands out of the warm dense phase, a stable degenerate
      plasma (T~1.2eV) with n_{e}>10^{17}cm^{-3} is measured for >100 ns. This is the
      first temporal measurement of the generation and adiabatic expansion of a large
      volume (3*10^{-4}cm^{3}) of warm dense plasma isochorically heated by intense
      monochromatic electrons. The suite of diagnostics is presented, which includes
      time-resolved plasma plume expansion measurements on a single shot, visible
      spectroscopy measurements of the emission and absorption spectrum, measurements
      of the beam distribution, and plans for the future.

PMID- 29347079
TI  - Optimal information transfer in enzymatic networks: A field theoretic
      formulation.
AB  - Signaling in enzymatic networks is typically triggered by environmental
      fluctuations, resulting in a series of stochastic chemical reactions, leading to
      corruption of the signal by noise. For example, information flow is initiated by
      binding of extracellular ligands to receptors, which is transmitted through a
      cascade involving kinase-phosphatase stochastic chemical reactions. For a class
      of such networks, we develop a general field-theoretic approach to calculate the
      error in signal transmission as a function of an appropriate control variable.
      Application of the theory to a simple push-pull network, a module in the kinase
      phosphatase cascade, recovers the exact results for error in signal transmission
      previously obtained using umbral calculus [Hinczewski and Thirumalai, Phys. Rev.
      X 4, 041017 (2014)2160-330810.1103/PhysRevX.4.041017]. We illustrate the
      generality of the theory by studying the minimal errors in noise reduction in a
      reaction cascade with two connected push-pull modules. Such a cascade behaves as
      an effective three-species network with a pseudointermediate. In this case,
      optimal information transfer, resulting in the smallest square of the error
      between the input and output, occurs with a time delay, which is given by the
      inverse of the decay rate of the pseudointermediate. Surprisingly, in these
      examples the minimum error computed using simulations that take nonlinearities
      and discrete nature of molecules into account coincides with the predictions of a
      linear theory. In contrast, there are substantial deviations between simulations
      and predictions of the linear theory in error in signal propagation in an
      enzymatic push-pull network for a certain range of parameters. Inclusion of
      second-order perturbative corrections shows that differences between simulations
      and theoretical predictions are minimized. Our study establishes that a field
      theoretic formulation of stochastic biological signaling offers a systematic way
      to understand error propagation in networks of arbitrary complexity.

PMID- 29347080
TI  - Derivation of stable Burnett equations for rarefied gas flows.
AB  - A set of constitutive relations for the stress tensor and heat flux vector for
      the hydrodynamic description of rarefied gas flows is derived in this work. A
      phase density function consistent with Onsager's reciprocity principle and H
      theorem is utilized to capture nonequilibrium thermodynamics effects. The phase
      density function satisfies the linearized Boltzmann equation and the collision
      invariance property. Our formulation provides the correct value of the Prandtl
      number as it involves two different relaxation times for momentum and energy
      transport by diffusion. Generalized three-dimensional constitutive equations for
      different kinds of molecules are derived using the phase density function. The
      derived constitutive equations involve cross single derivatives of field
      variables such as temperature and velocity, with no higher-order derivative in
      higher-order terms. This is remarkable feature of the equations as the number of
      boundary conditions required is the same as needed for conventional Navier-Stokes
      equations. Linear stability analysis of the equations is performed, which shows
      that the derived equations are unconditionally stable. A comparison of the
      derived equations with existing Burnett-type equations is presented and salient
      features of our equations are outlined. The classic internal flow problem, force
      driven compressible plane Poiseuille flow, is chosen to verify the stable Burnett
      equations and the results for equilibrium variables are presented.

PMID- 29347081
TI  - Phenomenological modeling of durotaxis.
AB  - Cells exhibit qualitatively different behaviors on substrates with different
      rigidities. The fact that cells are more polarized on the stiffer substrate
      motivates us to construct a two-dimensional cell with the distribution of focal
      adhesions dependent on substrate rigidities. This distribution affects the forces
      exerted by the cell and thereby determines its motion. Our model reproduces the
      experimental observation that the persistence time is higher on the stiffer
      substrate. This stiffness-dependent persistence will lead to durotaxis, the
      preference in moving towards stiffer substrates. This propensity is characterized
      by the durotaxis index first defined in experiments. We derive and validate a two
      dimensional corresponding Fokker-Planck equation associated with our model. Our
      approach highlights the possible role of the focal adhesion arrangement in
      durotaxis.

PMID- 29347082
TI  - Definite existence of subphases with eight- and ten-layer unit cells as studied
      by complementary methods, electric-field-induced birefringence and microbeam
      resonant x-ray scattering.
AB  - A mixture of two selenium-containing compounds, 80 wt. % AS657 and 20 wt. %
      AS620, are studied with two complementary methods, electric-field-induced
      birefringence (EFIB) and microbeam resonant x-ray scattering (MURXS). The mixture
      shows the typical phase sequence of Sm-C_{A}^{*}-1/3-1/2-Sm-C^{*}-Sm
      C_{alpha}^{*}-Sm-A, where 1/3 and 1/2 are two prototypal ferrielectric and
      antiferroelectric subphases with three- and four-layer unit cells, respectively.
      Here we designate the subphase as its q_{T} number defined by the ratio of
      [F]/([F]+[A]), where [F] and [A] are the numbers of synclinic ferroelectric and
      anticlinic antiferroelectric orderings in the unit cell, respectively. The
      electric field vs temperature phase diagram with EFIB contours indicates the
      emergence of three additional subphases, an antiferroelectric one between Sm
      C_{A}^{*} and 1/3 and antiferroelectric and apparently ferrielectric ones between
      1/3 and 1/2. The simplest probable q_{T}'s for these additional subphases are
      1/4, 2/5, and 3/7, respectively, in the order of increasing temperature. The
      MURXS profiles indicate that antiferroelectric 1/4 and 2/5 approximately have the
      eight-layer (FAAAFAAA) and ten-layer (FAFAAFAFAA) Ising unit cells, respectively.
      The remaining subphase may be ferrielectric 3/7 with a seven-layer unit cell,
      although the evidence is partial. These experimental results are compared with
      the phenomenological Landau model [P. V. Dolganov and E. I. Kats, Liq. Cryst.
      Rev. 1, 127 (2014)2168-039610.1080/21680396.2013.869667] and the quasimolecular
      model [A. V. Emelyanenko and M. A. Osipov, Phys. Rev. E 68, 051703 (2003)1063
      651X10.1103/PhysRevE.68.051703].

PMID- 29347083
TI  - Contact of a spherical probe with a stretched rubber substrate.
AB  - We report on a theoretical and experimental investigation of the normal contact
      of stretched neo-Hookean substrates with rigid spherical probes. Starting from a
      published formulation of surface Green's function for incremental displacements
      on a prestretched, neo-Hookean, substrate [J. Mech. Phys. Solids 56, 2957
      (2008)JMPSA80022-509610.1016/j.jmps.2008.07.002], a model is derived for both
      adhesive and nonadhesive contacts. The shape of the elliptical contact area
      together with the contact load and the contact stiffness are predicted as a
      function of the in-plane stretch ratios lambda_{x} and lambda_{y} of the
      substrate. The validity of this model is assessed by contact experiments carried
      out using an uniaxally stretched silicone rubber. For stretch ratio below about
      1.25, a good agreement is observed between theory and experiments. Above this
      threshold, some deviations from the theoretical predictions are induced as a
      result of the departure of the mechanical response of the silicone rubber from
      the neo-Hokeean description embedded in the model.

PMID- 29347084
TI  - Identifying the linear phase of the relativistic Kelvin-Helmholtz instability and
      measuring its growth rate via radiation.
AB  - For the relativistic Kelvin-Helmholtz instability (KHI), which occurs at shear
      interfaces between two plasma streams, we report results on the polarized
      radiation over all observation directions and frequencies emitted by the plasma
      electrons from ab initio kinetic simulations. We find the polarization of the
      radiation to provide a clear signature for distinguishing the linear phase of the
      KHI from its other phases. During the linear phase, we predict the growth rate of
      the KHI radiation power to match the growth rate of the KHI to a high degree. Our
      predictions are based on a model of the vortex dynamics, which describes the
      electron motion in the vicinity of the shear interface between the two streams.
      Albeit the complex and turbulent dynamics happening in the shear region, we find
      excellent agreement between our model and large-scale particle-in-cell
      simulations. Our findings pave the way for identifying the KHI linear regime and
      for measuring its growth rate in astrophysical jets observable on earth as well
      as in laboratory plasmas.

PMID- 29347085
TI  - Optimizing mutual synchronization of rhythmic spatiotemporal patterns in reaction
      diffusion systems.
AB  - Optimization of the stability of synchronized states between a pair of
      symmetrically coupled reaction-diffusion systems exhibiting rhythmic
      spatiotemporal patterns is studied in the framework of the phase reduction
      theory. The optimal linear filter that maximizes the linear stability of the in
      phase synchronized state is derived for the case in which the two systems are
      nonlocally coupled. The optimal nonlinear interaction function that theoretically
      gives the largest linear stability of the in-phase synchronized state is also
      derived. The theory is illustrated by using typical rhythmic patterns in FitzHugh
      Nagumo systems as examples.

PMID- 29347086
TI  - Aggregation-fragmentation-diffusion model for trail dynamics.
AB  - We investigate statistical properties of trails formed by a random process
      incorporating aggregation, fragmentation, and diffusion. In this stochastic
      process, which takes place in one spatial dimension, two neighboring trails may
      combine to form a larger one, and also one trail may split into two. In addition,
      trails move diffusively. The model is defined by two parameters which quantify
      the fragmentation rate and the fragment size. In the long-time limit, the system
      reaches a steady state, and our focus is the limiting distribution of trail
      weights. We find that the density of trail weight has power-law tail P(w)~w^{
      gamma} for small weight w. We obtain the exponent gamma analytically and find
      that it varies continuously with the two model parameters. The exponent gamma can
      be positive or negative, so that in one range of parameters small-weight trails
      are abundant and in the complementary range they are rare.

PMID- 29347087
TI  - Parallel random target searches in a confined space.
AB  - We study a random target searching performed by N independent searchers in a d
      dimensional domain of a large but finite volume. Considering the two initial
      distributions of searchers where searchers are either uniformly or point
      distributed, we estimate the mean time for the first of the searchers to reach
      the target and refer to it as searching time. The searching time for the
      uniformly distributed searchers exhibits a universal power-law dependence on N,
      irrespective of dimensionality and the target-to-domain size ratio. For point
      distributed searching, the searching time has a logarithmic dependence on N in
      the large N limit, while in the small N limit, it shows qualitatively different
      behaviors depending upon r_{0}, the initial distance of the searchers from a
      target. We obtain a diagram by comparing the searching times of the two initial
      distributions in the parameter space (r_{0},N) and therein present the asymptotic
      lines separating three characteristic regions to explain numerical simulation
      results.

PMID- 29347088
TI  - Effect of polymer additives on heat transport and large-scale circulation in
      turbulent Rayleigh-Benard convection.
AB  - The present paper presents direct numerical simulations of Rayleigh-Benard
      convection (RBC) in an enclosed cell filled with the polymer solution in order to
      investigate the viscoelastic effect on the characteristics of heat transport and
      large-scale circulation (LSC) of RBC. To overcome the difficulties in numerically
      solving a high Weissenberg number (Wi) problem of viscoelastic fluid flow with
      strong elastic effect, the log-conformation reformulation method was implemented.
      Numerical results showed that the addition of polymers reduced the heat flux and
      the amount of heat transfer reduction (HTR) behaves nonmonotonically, which
      firstly increases but then decreases with Wi. The maximum HTR reaches around 8.7%
      at the critical Wi. The nonmonotonic behavior of HTR as a function of Wi was then
      corroborated with the modifications of the period of LSC and turbulent energy as
      well as viscous boundary layer thickness. Finally, a standard turbulent kinetic
      energy (TKE) budget analysis was done for the whole domain, the boundary layer
      region, and the bulk region. It showed that the role change of elastic stress
      contributions to TKE is mainly responsible for this nonmonotonic behavior of HTR.

PMID- 29347089
TI  - Alternative steady states in ecological networks.
AB  - In many natural situations, one observes a local system with many competing
      species that is coupled by weak immigration to a regional species pool. The
      dynamics of such a system is dominated by its stable and uninvadable (SU) states.
      When the competition matrix is random, the number of SUs depends on the average
      value and variance of its entries. Here we consider the problem in the limit of
      weak competition and large variance. Using a yes-no interaction model, we show
      that the number of SUs corresponds to the number of maximum cliques in an Erdos
      Renyi network. The number of SUs grows exponentially with the number of species
      in this limit, unless the network is completely asymmetric. In the asymmetric
      limit, the number of SUs is O(1). Numerical simulations suggest that these
      results are valid for models with a continuous distribution of competition terms.

PMID- 29347090
TI  - Phase-field lattice Boltzmann modeling of boiling using a sharp-interface energy
      solver.
AB  - The main objective of this paper is to extend an isothermal incompressible two
      phase lattice Boltzmann equation method to model liquid-vapor phase change
      problems using a sharp-interface energy solver. Two discrete particle
      distribution functions, one for the continuity equation and the other for the
      pressure evolution and momentum equations, are considered in the current model.
      The sharp-interface macroscopic internal energy equation is discretized with an
      isotropic finite difference method to find temperature distribution in the
      system. The mass flow generated at liquid-vapor phase interface is embedded in
      the pressure evolution equation. The sharp-interface treatment of internal energy
      equation helps to find the interfacial mass flow rate accurately where no free
      parameter is needed in the calculations. The proposed model is verified against
      available theoretical solutions of the two-phase Stefan problem and the two-phase
      sucking interface problem, with which our simulation results are in good
      agreement. The liquid droplet evaporation in a superheated vapor, the vapor
      bubble growth in a superheated liquid, and the vapor bubble rising in a
      superheated liquid are analyzed and underlying physical characteristics are
      discussed in detail. The model is successfully tested for the liquid-vapor phase
      change with large density ratio up to 1000.

PMID- 29347091
TI  - Graph spectral characterization of the XY model on complex networks.
AB  - There is recent evidence that the XY spin model on complex networks can display
      three different macroscopic states in response to the topology of the network
      underpinning the interactions of the spins. In this work we present a way to
      characterize the macroscopic states of the XY spin model based on the spectral
      decomposition of time series using topological information about the underlying
      networks. We use three different classes of networks to generate time series of
      the spins for the three possible macroscopic states. We then use the temporal
      Graph Signal Transform technique to decompose the time series of the spins on the
      eigenbasis of the Laplacian. From this decomposition, we produce spatial power
      spectra, which summarize the activation of structural modes by the nonlinear
      dynamics, and thus coherent patterns of activity of the spins. These signatures
      of the macroscopic states are independent of the underlying network class and can
      thus be used as robust signatures for the macroscopic states. This work opens
      avenues to analyze and characterize dynamics on complex networks using temporal
      Graph Signal Analysis.

PMID- 29347092
TI  - Front roughening of flames in discrete media.
AB  - The morphology of flame fronts propagating in reactive systems composed of
      randomly positioned, pointlike sources is studied. The solution of the
      temperature field and the initiation of new sources is implemented using the
      superposition of the Green's function for the diffusion equation, eliminating the
      need to use finite-difference approximations. The heat released from triggered
      sources diffuses outward from each source, activating new sources and enabling a
      mechanism of flame propagation. Systems of 40000 sources in a 200*200 two
      dimensional domain were tracked using computer simulations, and statistical
      ensembles of 120 realizations of each system were averaged to determine the
      statistical properties of the flame fronts. The reactive system of sources is
      parameterized by two nondimensional values: the heat release time (normalized by
      interparticle diffusion time) and the ignition temperature (normalized by
      adiabatic flame temperature). These two parameters were systematically varied for
      different simulations to investigate their influence on front propagation. For
      sufficiently fast heat release and low ignition temperature, the front roughness
      [defined as the root mean square deviation of the ignition temperature contour
      from the average flame position] grew following a power-law dependence that was
      in excellent agreement with the Kardar-Parisi-Zhang (KPZ) universality class
      (beta=1/3). As the reaction time was increased, lower values of the roughening
      exponent were observed, and at a sufficiently great value of reaction time,
      reversion to a steady, constant-width thermal flame was observed that matched the
      solution from classical combustion theory. Deviation away from KPZ scaling was
      also observed as the ignition temperature was increased. The features of this
      system that permit it to exhibit both KPZ and non-KPZ scaling are discussed.

PMID- 29347093
TI  - Self-assembly of rigid magnetic rods consisting of single dipolar beads in two
      dimensions.
AB  - Molecular dynamics simulations are used to investigate the structural properties
      of a two-dimensional ensemble of magnetic rods, which are modeled as aligned
      single dipolar beads. The obtained self-assembled configurations can be
      characterized as (1) clusters, (2) percolated, and (3) ordered structures, and
      their structural properties are investigated in detail. By increasing the aspect
      ratio of the magnetic rods, we show that the percolation transition is suppressed
      due to the reduced mobility of the rods in two dimensions. Such a behavior is
      opposite to the one observed in three dimensions. A magnetic bulk phase is found
      with local ferromagnetic order and an unusual nonmonotonic behavior of the
      nematic order is observed.

PMID- 29347094
TI  - Perturbation scheme for a fluxon in a curved Josephson junction.
AB  - The kink solution in the long Josephson junction is studied. The perturbation
      scheme of constructing the fluxon solution in curved junction is formulated. The
      prediction from the perturbation scheme is compared with the prediction that
      follows from the numerical studies of the complete field model.

PMID- 29347095
TI  - Viscorotational shear instability of Keplerian granular flows.
AB  - The linear stability of viscous Keplerian flow around a gravitating center is
      studied using the rheological granular fluid model. The linear rheological
      instability triggered by the interplay of the shear rheology and Keplerian
      differential rotation of incompressible dense granular fluids is found.
      Instability sets in in granular fluids, where the viscosity parameter grows
      faster than the square of the local shear rate (strain rate) at constant
      pressure. Found instability can play a crucial role in the dynamics of dense
      planetary rings and granular flows in protoplanetary disks.

PMID- 29347096
TI  - Random blebbing motion: A simple model linking cell structural properties to
      migration characteristics.
AB  - If the plasma membrane of a cell is able to delaminate locally from its actin
      cortex, a cellular bleb can be produced. Blebs are pressure-driven protrusions,
      which are noteworthy for their ability to produce cellular motion. Starting from
      a general continuum mechanics description, we restrict ourselves to considering
      cell and bleb shapes that maintain approximately spherical forms. From this
      assumption, we obtain a tractable algebraic system for bleb formation. By
      including cell-substrate adhesions, we can model blebbing cell motility. Further,
      by considering mechanically isolated blebbing events, which are randomly
      distributed over the cell, we can derive equations linking the macroscopic
      migration characteristics to the microscopic structural parameters of the cell.
      This multiscale modeling framework is then used to provide parameter estimates,
      which are in agreement with current experimental data. In summary, the
      construction of the mathematical model provides testable relationships between
      the bleb size and cell motility.

PMID- 29347097
TI  - Extreme and superextreme events in a loss-modulated CO_{2} laser: Nonlinear
      resonance route and precursors.
AB  - We investigate the occurrence of extreme and rare events, i.e., giant and rare
      light pulses, in a periodically modulated CO_{2} laser model. Due to nonlinear
      resonant processes, we show a scenario of interaction between chaotic bands of
      different orders, which may lead to the formation of extreme and rare events. We
      identify a crisis line in the modulation parameter space, and we show that, when
      the modulation amplitude increases, remaining in the vicinity of the crisis, some
      statistical properties of the laser pulses, such as the average and dispersion of
      amplitudes, do not change much, whereas the amplitude of extreme events grows
      enormously, giving rise to extreme events with much larger deviations than
      usually reported, with a significant probability of occurrence, i.e., with a long
      tailed non-Gaussian distribution. We identify recurrent regular patterns, i.e.,
      precursors, that anticipate the emergence of extreme and rare events, and we
      associate these regular patterns with unstable periodic orbits embedded in a
      chaotic attractor. We show that the precursors may or may not lead to the
      emergence of extreme events. Thus, we compute the probability of success or
      failure (false alarm) in the prediction of the extreme events, once a precursor
      is identified in the deterministic time series. We show that this probability
      depends on the accuracy with which the precursor is identified in the laser
      intensity time series.

PMID- 29347098
TI  - Statistics of randomly cross-linked polymer models to interpret chromatin
      conformation capture data.
AB  - Polymer models are used to describe chromatin, which can be folded at different
      spatial scales by binding molecules. By folding, chromatin generates loops of
      various sizes. We present here a statistical analysis of the randomly cross
      linked (RCL) polymer model, where monomer pairs are connected randomly,
      generating a heterogeneous ensemble of chromatin conformations. We obtain
      asymptotic formulas for the steady-state variance, encounter probability, the
      radius of gyration, instantaneous displacement, and the mean first encounter time
      between any two monomers. The analytical results are confirmed by Brownian
      simulations. Finally, the present results are used to extract the mean number of
      cross links in a chromatin region from conformation capture data.

PMID- 29347099
TI  - Heat engines at optimal power: Low-dissipation versus endoreversible model.
AB  - The low-dissipation model and the endoreversible model of heat engines are two of
      the most commonly studied models of machines in finite-time thermodynamics. In
      this paper we compare the performance characteristics of these two models under
      optimal power output. We point out a basic equivalence between them, in the
      linear response regime.

PMID- 29347100
TI  - Correcting binding parameters for interacting ligand-lattice systems.
AB  - Binding of ligands to macromolecules is central to many functional and regulatory
      biological processes. Key parameters characterizing ligand-macromolecule
      interactions are the stoichiometry, inducing the number of ligands per
      macromolecule binding site, and the dissociation constant, quantifying the ligand
      binding site affinity. Both these parameters can be obtained from analyses of
      classical saturation experiments using the standard binding equation that offers
      the great advantage of mathematical simplicity but becomes an approximation for
      situations of interest when a ligand binds and covers more than one single
      binding site on the macromolecule. Using the framework of car-parking problem
      with latticelike macromolecules where each ligand can cover simultaneously
      several consecutive binding sites, we showed that employing the standard analysis
      leads to underestimation of binding parameters, i.e., ligands appear larger than
      they actually are and their affinity is also greater than it is. Therefore, we
      have derived expressions allowing to determine the ligand size and true binding
      parameters (stoichiometry and dissociation constant) as a function of apparent
      binding parameters retrieved from standard saturation experiments.

PMID- 29347101
TI  - Formation of liquid drops at an orifice and dynamics of pinch-off in liquid jets.
AB  - This paper presents a numerical investigation of the dynamics of pinch-off in
      liquid drops and jets during injection of a liquid through an orifice into
      another fluid. The current study is carried out by solving axisymmetric Navier
      Stokes equations and the interface is captured using a coupled level-set and
      volume-of-fluid approach. The delicate interplay of inertia and viscous effects
      plays a crucial role in deciding the dynamics of the formation as well as breakup
      of liquid drops and jets. In the dripping regime, the growth and breakup rate of
      a drop are studied and quantified by corroborating with theoretical predictions.
      During the growth stage of the drops, a self-similar behavior of the drop profile
      is identified over a relatively short duration of time. The viscosity of the drop
      liquid shows substantial influence on the thinning behavior of a liquid neck and
      a transition is observed from an inertia dominated regime to an inertia-viscous
      regime beyond a critical minimum value of the neck radius. The phenomenon of
      interface overturning is fundamentally related to the magnitude of drop
      viscosity. The variation of overturning angle as a function of drop viscosity is
      computed and a critical value of Ohnesorge number is obtained beyond which
      overturning ceases. Increasing the inertia of drop liquid transforms the system
      from a periodically dripping regime to a quasiperiodic regime and finally it
      culminates into an elongated liquid jet. Another interesting transition from
      dripping to jetting regime is demonstrated by varying the viscosity of the
      ambient medium. The breakup of jets in Rayleigh mode is explored and the breakup
      length obtained from our computations shows excellent agreement with the
      theoretical predictions owing to Rayleigh's analysis. The ambient medium is
      entrained as the jet moves downstream with the creation of a vortical structure
      just outside the jet signifying increased participation of the ambient medium in
      the dynamics of jet breakup at higher inflow rates.

PMID- 29347102
TI  - Crack-tip process zone as a bifurcation problem.
AB  - Stress concentration at a crack tip generates a solid structural transformation
      in its vicinity, the process zone. We argue that its formation represents a local
      phase transition described by a multicomponent order parameter. We derive a
      system of equations describing the dynamics of the order parameter driven by an
      inhomogeneous, time-dependent stress field in the solid and show that it exhibits
      a bifurcation. The latter corresponds to the emergence of a process zone
      characterized by the distribution of the order parameter localized in the
      vicinity of the crack tip. The emergence temperature T_{*} considerably differs
      from the temperature of the bulk phase transformation T_{c}. We demonstrate that
      T_{*} exhibits a universal behavior T_{*}-T_{c}~K_{I}^{4/3}, in terms of the
      stress intensity factor K_{I}, and that the zone universally vanishes upon
      achieving a critical velocity. These facts together give rise to a universal
      dynamic phase diagram.

PMID- 29347103
TI  - Shortcuts to isothermality and nonequilibrium work relations.
AB  - In conventional thermodynamics, it is widely acknowledged that the realization of
      an isothermal process for a system requires a quasistatic controlling protocol.
      Here we propose and design a strategy to realize a finite-rate isothermal
      transition from an equilibrium state to another one at the same temperature,
      which is named the "shortcut to isothermality." By using shortcuts to
      isothermality, we derive three nonequilibrium work relations, including an
      identity between the free-energy difference and the mean work due to the
      potential of the original system, a Jarzynski-like equality, and the inverse
      relationship between the dissipated work and the total driving time. We
      numerically test these three relations by considering the motion of a Brownian
      particle trapped in a harmonic potential and dragged by a time-dependent force.

PMID- 29347104
TI  - Visibility graphs of random scalar fields and spatial data.
AB  - We extend the family of visibility algorithms to map scalar fields of arbitrary
      dimension into graphs, enabling the analysis of spatially extended data
      structures as networks. We introduce several possible extensions and provide
      analytical results on the topological properties of the graphs associated to
      different types of real-valued matrices, which can be understood as the high and
      low disorder limits of real-valued scalar fields. In particular, we find a closed
      expression for the degree distribution of these graphs associated to uncorrelated
      random fields of generic dimension. This result holds independently of the
      field's marginal distribution and it directly yields a statistical randomness
      test, applicable in any dimension. We showcase its usefulness by discriminating
      spatial snapshots of two-dimensional white noise from snapshots of a two
      dimensional lattice of diffusively coupled chaotic maps, a system that generates
      high dimensional spatiotemporal chaos. The range of potential applications of
      this combinatorial framework includes image processing in engineering, the
      description of surface growth in material science, soft matter or medicine, and
      the characterization of potential energy surfaces in chemistry, disordered
      systems, and high energy physics. An illustration on the applicability of this
      method for the classification of the different stages involved in carcinogenesis
      is briefly discussed.

PMID- 29347105
TI  - Lattice gas with molecular dynamics collision operator.
AB  - We introduce a lattice gas implementation that is based on coarse-graining a
      molecular dynamics (MD) simulation. Such a lattice gas is similar to standard
      lattice gases, but its collision operator is informed by an underlying MD
      simulation. This can be considered an optimal lattice gas implementation because
      it allows for the representation of any system that can be simulated with MD. We
      show here that equilibrium behavior of the popular lattice Boltzmann algorithm is
      consistent with this optimal lattice gas. This comparison allows us to make a
      more accurate identification of the expressions for temperature and pressure in
      lattice Boltzmann simulations, which turn out to be related not only to the
      physical temperature and pressure but also to the lattice discretization. We show
      that for any spatial discretization, we need to choose a particular temporal
      discretization to recover the lattice Boltzmann equilibrium.

PMID- 29347106
TI  - Criticality in Brownian ensembles.
AB  - A Brownian ensemble appears as a nonequilibrium state of transition from one
      universality class of random matrix ensembles to another one. The parameter
      governing the transition is, in general, size-dependent, resulting in a rapid
      approach of the statistics, in infinite size limit, to one of the two
      universality classes. Our detailed analysis, however, reveals the appearance of a
      new scale-invariant spectral statistics, nonstationary along the spectrum,
      associated with multifractal eigenstates, and different from the two end-points
      if the transition parameter becomes size-independent. The number of such critical
      points during transition is governed by a competition between the average
      perturbation strength and the local spectral density. The results obtained here
      have applications to wide-ranging complex systems, e.g., those modeled by
      multiparametric Gaussian ensembles or column constrained ensembles.

PMID- 29347107
TI  - Hawkes process model with a time-dependent background rate and its application to
      high-frequency financial data.
AB  - A Hawkes process model with a time-varying background rate is developed for
      analyzing the high-frequency financial data. In our model, the logarithm of the
      background rate is modeled by a linear model with a relatively large number of
      variable-width basis functions, and the parameters are estimated by a Bayesian
      method. Our model can capture not only the slow time variation, such as in the
      intraday seasonality, but also the rapid one, which follows a macroeconomic news
      announcement. By analyzing the tick data of the Nikkei 225 mini, we find that (i)
      our model is better fitted to the data than the Hawkes models with a constant
      background rate or a slowly varying background rate, which have been commonly
      used in the field of quantitative finance; (ii) the improvement in the goodness
      of-fit to the data by our model is significant especially for sessions where
      considerable fluctuation of the background rate is present; and (iii) our model
      is statistically consistent with the data. The branching ratio, which quantifies
      the level of the endogeneity of markets, estimated by our model is 0.41,
      suggesting the relative importance of exogenous factors in the market dynamics.
      We also demonstrate that it is critically important to appropriately model the
      time-dependent background rate for the branching ratio estimation.

PMID- 29347108
TI  - In silico optimization of critical currents in superconductors.
AB  - For many technological applications of superconductors the performance of a
      material is determined by the highest current it can carry losslessly-the
      critical current. In turn, the critical current can be controlled by adding
      nonsuperconducting defects in the superconductor matrix. Here we report on
      systematic comparison of different local and global optimization strategies to
      predict optimal structures of pinning centers leading to the highest possible
      critical currents. We demonstrate performance of these methods for a
      superconductor with randomly placed spherical, elliptical, and columnar defects.

PMID- 29347109
TI  - Traveling waves in a spring-block chain sliding down a slope.
AB  - Traveling waves are studied in a spring slider-block model. We explicitly
      construct front waves (kinks) for a piecewise-linear spinodal friction force.
      Pulse waves are obtained as the matching of two traveling fronts with identical
      speeds. Explicit formulas are obtained for the wavespeed and the wave form in the
      anticontinuum limit. The link with localized waves in a Burridge-Knopoff model of
      an earthquake fault is briefly discussed.

PMID- 29347110
TI  - Influence of a dispersion of magnetic and nonmagnetic nanoparticles on the
      magnetic Fredericksz transition of the liquid crystal 5CB.
AB  - A long time ago, Brochard and de Gennes predicted the possibility of
      significantly decreasing the critical magnetic field of the Fredericksz
      transition (the magnetic Fredericksz threshold) in a mixture of nematic liquid
      crystals and ferromagnetic particles, the so-called ferronematics. This
      phenomenon is rarely measured to be large, due to soft homeotropic anchoring
      induced at the nanoparticle surface. Here we present an optical study of the
      magnetic Fredericksz transition combined with a light scattering study of the
      classical nematic liquid crystal: the pentylcyanobiphenyl (5CB), doped with 6 nm
      diameter magnetic and nonmagnetic nanoparticles. Surprisingly, for both
      nanoparticles, we observe at room temperature a net decrease of the threshold
      field of the Fredericksz transition at low nanoparticle concentrations, which
      appears associated with a coating of the nanoparticles by a brush of
      polydimethylsiloxane copolymer chains inducing planar anchoring of the director
      on the nanoparticle surface. Moreover, the magnetic Fredericksz threshold
      exhibits nonmonotonic behavior as a function of the nanoparticle concentration
      for both types of nanoparticles, first decreasing down to a value from 23% to 31%
      below that of pure 5CB, then increasing with a further increase of nanoparticle
      concentration. This is interpreted as an aggregation starting at around 0.02
      weight fraction that consumes more isolated nanoparticles than those introduced
      when the concentration is increased above c=0.05 weight fraction (volume fraction
      3.5*10^{-2}). This shows the larger effect of isolated nanoparticles on the
      threshold with respect to aggregates. From dynamic light scattering measurements
      we deduced that, if the decrease of the magnetic threshold when the nanoparticle
      concentration increases is similar for both kinds of nanoparticles, the origin of
      this decrease is different for magnetic and nonmagnetic nanoparticles. For
      nonmagnetic nanoparticles, the behavior may be associated with a decrease of the
      elastic constant due to weak planar anchoring. For magnetic nanoparticles there
      are non-negligible local magnetic interactions between liquid crystal molecules
      and magnetic nanoparticles, leading to an increase of the average order
      parameter. This magnetic interaction thus favors an easier liquid crystal
      director rotation in the presence of external magnetic field, able to reorient
      the magnetic moments of the nanoparticles along with the molecules.

PMID- 29347111
TI  - Eigenstate thermalization in the two-dimensional transverse field Ising model.
      II. Off-diagonal matrix elements of observables.
AB  - We study the matrix elements of few-body observables, focusing on the off
      diagonal ones, in the eigenstates of the two-dimensional transverse field Ising
      model. By resolving all symmetries, we relate the onset of quantum chaos to the
      structure of the matrix elements. In particular, we show that a general result of
      the theory of random matrices, namely, the value 2 of the ratio of variances
      (diagonal to off-diagonal) of the matrix elements of Hermitian operators, occurs
      in the quantum chaotic regime. Furthermore, we explore the behavior of the off
      diagonal matrix elements of observables as a function of the eigenstate energy
      differences and show that it is in accordance with the eigenstate thermalization
      hypothesis ansatz.

PMID- 29347112
TI  - Statistics, distillation, and ordering emergence in a two-dimensional stochastic
      model of particles in counterflowing streams.
AB  - In this paper, we propose a stochastic model which describes two species of
      particles moving in counterflow. The model generalizes the theoretical framework
      that describes the transport in random systems by taking into account two
      different scenarios: particles can work as mobile obstacles, whereas particles of
      one species move in the opposite direction to the particles of the other species,
      or particles of a given species work as fixed obstacles remaining in their places
      during the time evolution. We conduct a detailed study about the statistics
      concerning the crossing time of particles, as well as the effects of the lateral
      transitions on the time required to the system reaches a state of complete
      geographic separation of species. The spatial effects of jamming are also studied
      by looking into the deformation of the concentration of particles in the two
      dimensional corridor. Finally, we observe in our study the formation of patterns
      of lanes which reach the steady state regardless of the initial conditions used
      for the evolution. A similar result is also observed in real experiments
      involving charged colloids motion and simulations of pedestrian dynamics based on
      Langevin equations, when periodic boundary conditions are considered (particles
      counterflow in a ring symmetry). The results obtained through Monte Carlo
      simulations and numerical integrations are in good agreement with each other.
      However, differently from previous studies, the dynamics considered in this work
      is not Newton-based, and therefore, even artificial situations of self-propelled
      objects should be studied in this first-principles modeling.

PMID- 29347113
TI  - Counting statistics of chaotic resonances at optical frequencies: Theory and
      experiments.
AB  - A deformed dielectric microcavity is used as an experimental platform for the
      analysis of the statistics of chaotic resonances, in the perspective of testing
      fractal Weyl laws at optical frequencies. In order to surmount the difficulties
      that arise from reading strongly overlapping spectra, we exploit the mixed nature
      of the phase space at hand, and only count the high-Q whispering-gallery modes
      (WGMs) directly. That enables us to draw statistical information on the more
      lossy chaotic resonances, coupled to the high-Q regular modes via dynamical
      tunneling. Three different models [classical, Random-Matrix-Theory (RMT) based,
      semiclassical] to interpret the experimental data are discussed. On the basis of
      least-squares analysis, theoretical estimates of Ehrenfest time, and independent
      measurements, we find that a semiclassically modified RMT-based expression best
      describes the experiment in all its realizations, particularly when the resonator
      is coupled to visible light, while RMT alone still works quite well in the
      infrared. In this work we reexamine and substantially extend the results of a
      short paper published earlier [L. Wang et al., Phys. Rev. E 93, 040201(R)
      (2016)2470-004510.1103/PhysRevE.93.040201].

PMID- 29347114
TI  - Passive scalar transport by a non-Gaussian turbulent flow in the Batchelor
      regime.
AB  - We analyze passive scalar advection by a turbulent flow in the Batchelor regime.
      No restrictions on the velocity statistics of the flow are assumed. The
      properties of the scalar are derived from the statistical properties of velocity;
      analytic expressions for the moments of scalar density are obtained. We show that
      the scalar statistics can differ significantly from that obtained in the frames
      of the Kraichnan model.

PMID- 29347115
TI  - Multiple-relaxation-time lattice Boltzmann simulation for flow, mass transfer,
      and adsorption in porous media.
AB  - In this paper, to predict the dynamics behaviors of flow and mass transfer with
      adsorption phenomena in porous media at the representative elementary volume
      (REV) scale, a multiple-relaxation-time (MRT) lattice Boltzmann (LB) model for
      the convection-diffusion equation is developed to solve the transfer problem with
      an unsteady source term in porous media. Utilizing the Chapman-Enskog analysis,
      the modified MRT-LB model can recover the macroscopic governing equations at the
      REV scale. The coupled MRT-LB model for momentum and mass transfer is validated
      by comparing with the finite-difference method and the analytical solution.
      Moreover, using the MRT-LB method coupled with the linear driving force model,
      the fluid transfer and adsorption behaviors of the carbon dioxide in a porous
      fixed bed are explored. The breakthrough curve of adsorption from MRT-LB
      simulation is compared with the experimental data and the finite-element
      solution, and the transient concentration distributions of the carbon dioxide
      along the porous fixed bed are elaborated upon in detail. In addition, the MRT-LB
      simulation results show that the appearance time of the breakthrough point in the
      breakthrough curve is advanced as the mass transfer resistance in the linear
      driving force model increases; however, the saturation point is prolonged
      inversely.

PMID- 29347116
TI  - Orientational dynamics of fluctuating dipolar particles assembled in a mesoscopic
      colloidal ribbon.
AB  - We combine experiments and theory to investigate the dynamics and orientational
      fluctuations of ferromagnetic microellipsoids that form a ribbonlike structure
      due to attractive dipolar forces. When assembled in the ribbon, the ellipsoids
      display orientational thermal fluctuations with an amplitude that can be
      controlled via application of an in-plane magnetic field. We use video microscopy
      to investigate the orientational dynamics in real time and space. Theoretical
      arguments are used to derive an analytical expression that describes how the
      distribution of the different angular configurations depends on the strength of
      the applied field. The experimental data are in good agreement with the developed
      model for all the range of field parameters explored. Understanding the role of
      fluctuations in chains composed of dipolar particles is important not only from a
      fundamental point of view, but it may also help understanding the stability of
      such structures against thermal noise, which is relevant in microfluidics and
      laboratory-on-a-chip applications.

PMID- 29347117
TI  - Molecular-dynamics study on characteristics of energy and tangential momentum
      accommodation coefficients.
AB  - Gas-surface interaction is studied by the molecular dynamics method to
      investigate qualitatively characteristics of accommodation coefficients. A large
      number of trajectories of gas molecules colliding to and scattering from a
      surface are statistically analyzed to calculate the energy (thermal)
      accommodation coefficient (EAC) and the tangential momentum accommodation
      coefficient (TMAC). Considering experimental measurements of the accommodation
      coefficients, the incident velocities are stochastically sampled to represent a
      bulk condition. The accommodation coefficients for noble gases show qualitative
      coincidence with experimental values. To investigate characteristics of these
      accommodation coefficients in detail, the gas-surface interaction is
      parametrically studied by varying the molecular mass of gas, the gas-surface
      interaction strength, and the molecular size of gas, one by one. EAC increases
      with increasing every parameter, while TMAC increases with increasing the
      interaction strength, but decreases with increasing the molecular mass and the
      molecular size. Thus, contradictory results in experimentally measured TMAC for
      noble gases could result from the difference between the surface conditions
      employed in the measurements in the balance among the effective parameters of
      molecular mass, interaction strength, and molecular size, due to surface
      roughness and/or adsorbed molecules. The accommodation coefficients for a thermo
      fluid dynamics field with a temperature difference between gas and surface and a
      bulk flow at the same time are also investigated.

PMID- 29347118
TI  - Linear stability of layered two-phase flows through parallel soft-gel-coated
      walls.
AB  - The linear stability of layered two-phase Poiseuille flows through soft-gel
      coated parallel walls is studied in this work. The focus is on determining the
      effect of the elastohydrodynamic coupling between the fluids and the soft-gel
      layers on the different instabilities observed in flows between parallel plates.
      The fluids are assumed Newtonian and incompressible, while the soft gels are
      modeled as linear viscoelastic solids. A long-wave asymptotic analysis is used to
      obtain an analytical expression for the growth rate of the disturbances. A
      Chebyshev collocation method is used to numerically solve the general linearized
      equations. Three distinct instability modes are identified in the flow: (a) a
      liquid-liquid long-wave mode; (b) a liquid-liquid short-wave mode; (c) a gel
      liquid short-wave mode. The effect of deformability of the soft gels on these
      three modes is analyzed. From the long-wave analysis of the liquid-liquid mode a
      stability map is obtained, in which four different regions are clearly
      demarcated. It is shown that introducing a gel layer near the more viscous fluid
      has a predominantly stabilizing effect on this mode seen in flows between rigid
      plates. For parameters where this mode is stable for flow between rigid plates,
      introducing a gel layer near the less viscous and thinner fluid has a
      predominantly destabilizing effect. The liquid-liquid short-wave mode is
      destabilized by the introduction of soft-gel layers. Additional instability modes
      at the gel-liquid interfaces induced by the deformability of the soft-gel layers
      are identified. We show that these can be controlled by varying the thickness of
      the gel layers. Insights into the physical mechanism driving different
      instabilities are obtained using an energy budget analysis.

PMID- 29347119
TI  - Disentangling structural information from core-level excitation spectra.
AB  - Core-level spectra of liquids can be difficult to interpret due to the presence
      of a range of local environments. We present computational methods for
      investigating core-level spectra based on the idea that both local structural
      parameters and the x-ray spectra behave as functions of the local atomic
      configuration around the absorbing site. We identify correlations between
      structural parameters and spectral intensities in defined regions of interest,
      using the oxygen K-edge excitation spectrum of liquid water as a test case. Our
      results show that this kind of analysis can find the main structure-spectral
      relationships of ice, liquid water, and supercritical water.

PMID- 29347120
TI  - Microscopic muon dynamics in the polymer electrolyte poly(ethylene oxide).
AB  - The microscopic dynamics of protons (H^{+}) in poly(ethylene oxide) (PEO) have
      been investigated through a study of implanted positive muons (Mu^{+}), which can
      be considered a light proton analog. The exponential decay of the muon spin
      polarization in zero magnetic field indicated that Mu^{+} hopping is in the fast
      fluctuation limit between 140 and 310 K and the relaxation rate was found to be
      sensitive to the glass transition. Mu^{+} dynamics in PEO was monitored via the
      relaxation of the muon spin polarization in a transverse field of 10 mT.
      Activated hopping of Mu^{+} was observed above the glass transition temperature
      with an activation barrier of 122+/-1 meV. The temperature dependence of the
      diamagnetic muon polarization in PEO can be explained by diffusion of radiolytic
      electrons.

PMID- 29347121
TI  - Recurrence in the high-order nonlinear Schrodinger equation: A low-dimensional
      analysis.
AB  - We study a three-wave truncation of the high-order nonlinear Schrodinger equation
      for deep-water waves (also named Dysthe equation). We validate the model by
      comparing it to numerical simulation; we distinguish the impact of the different
      fourth-order terms and classify the solutions according to their topology. This
      allows us to properly define the temporary spectral upshift occurring in the
      nonlinear stage of Benjamin-Feir instability and provides a tool for studying
      further generalizations of this model.

PMID- 29347122
TI  - Impact of the kinetic boundary condition on porous media flow in the lattice
      Boltzmann formulation.
AB  - To emphasize the importance of the kinetic boundary condition for micro- to
      nanoscale flow, we present an ad hoc kinetic boundary condition suitable for
      torturous geological porous media. We found that the kinetic boundary condition
      is one of the essential features which should be supplemented to the standard
      lattice Boltzmann scheme in order to obtain accurate continuum observables. The
      claim is validated using a channel flow setup by showing the agreement of mass
      flux with analytical value. Further, using a homogeneous porous structure, the
      importance of the kinetic boundary condition is shown by comparing the
      permeability correction factor with the analytical value. Finally, the proposed
      alternate to the kinetic boundary condition is validated by showing its
      capability to capture the basic feature of the kinetic boundary condition.

PMID- 29347123
TI  - Dislocation-free growth of quasicrystals from two seeds due to additional
      phasonic degrees of freedom.
AB  - We explore the growth of two-dimensional quasicrystals, i.e., aperiodic
      structures that possess long-range order, from two seeds at various distances and
      with different orientations by using dynamical phase-field crystal calculations.
      We compare the results to the growth of periodic crystals from two seeds. There,
      a domain border consisting of dislocations is observed in case of large distances
      between the seed and large angles between their orientation. Furthermore, a
      domain border is found if the seeds are placed at a distance that does not fit to
      the periodic lattice. In the case of the growth of quasicrystals, we only observe
      domain borders for large distances and different orientations. Note that all
      distances do inherently not match to a perfect domain wall-free quasicrystalline
      structure. Nevertheless, we find dislocation-free growth for all seeds at a small
      enough distance and for all seeds that approximately have the same orientation.
      In periodic structures, the stress that occurs due to incommensurate distances
      between the seeds results in phononic strain fields or, in the case of too large
      stresses, in dislocations. In contrast, in quasicrystals an additional phasonic
      strain field can occur and suppress dislocations. Phasons are additional degrees
      of freedom that are unique to quasicrystals. As a consequence, the additional
      phasonic strain field helps to distribute the stress and facilitates the growth
      of dislocation-free quasicrystals from multiple seeds. In contrast, in the
      periodic case the growth from multiple seeds most likely leads to a structure
      with multiple domains. Our work lays the theoretical foundations for growing
      perfect quasicrystals from different seeds and is therefore relevant for many
      applications.

PMID- 29347124
TI  - Controllability of flow-conservation networks.
AB  - The ultimate goal of exploring complex networks is to control them. As such,
      controllability of complex networks has been intensively investigated. Despite
      recent advances in studying the impact of a network's topology on its
      controllability, a comprehensive understanding of the synergistic impact of
      network topology and dynamics on controllability is still lacking. Here, we
      explore the controllability of flow-conservation networks, trying to identify the
      minimal number of driver nodes that can guide the network to any desirable state.
      We develop a method to analyze the controllability on flow-conservation networks
      based on exact controllability theory, transforming the original analysis on
      adjacency matrix to Laplacian matrix. With this framework, we systematically
      investigate the impact of some key factors of networks, including link density,
      link directionality, and link polarity, on the controllability of these networks.
      We also obtain the analytical equations by investigating the network's structural
      properties approximatively and design the efficient tools. Finally, we consider
      some real networks with flow dynamics, finding that their controllability is
      significantly different from that predicted by only considering the topology.
      These findings deepen our understanding of network controllability with flow
      conservation dynamics and provide a general framework to incorporate real
      dynamics in the analysis of network controllability.

PMID- 29347125
TI  - Interplay of different environments in open quantum systems: Breakdown of the
      additive approximation.
AB  - We analyze an open quantum system under the influence of more than one
      environment: a dephasing bath and a probability-absorbing bath that represents a
      decay channel, as encountered in many models of quantum networks. In our case,
      dephasing is modeled by random fluctuations of the site energies, while the
      absorbing bath is modeled with an external lead attached to the system. We
      analyze under which conditions the effects of the two baths can enter additively
      the quantum master equation. When such additivity is legitimate, the reduced
      master equation corresponds to the evolution generated by an effective non
      Hermitian Hamiltonian and a Haken-Strobl dephasing super-operator. We find that
      the additive decomposition is a good approximation when the strength of dephasing
      is small compared to the bandwidth of the probability-absorbing bath.

PMID- 29347126
TI  - Requisite ingredients for thermal rectification.
AB  - The present work is devoted to an analytical investigation of the thermal
      rectification mechanism. More specifically, we attempt to find the requisite
      ingredients for such a phenomenon to occur. Starting from the linearization of
      the time evolution equations of anharmonic chains of oscillators, we propose some
      effective harmonic toy models with a potential that is dependent on temperature,
      and we investigate their steady heat currents. This unusual temperature-dependent
      potential is the footprint of nonlinearity in the final effective linear model.
      The approach is not restricted to any particular regime of heat transport. Our
      results show that thermal rectification holds in a system if it has asymmetric
      parameters related to its own structure, e.g., a graded particle mass
      distribution and some other parameters or features dependent on the inner
      temperatures that change as we invert the baths at the boundaries. The
      description of rectification in these simplified models, with minimal
      ingredients, shows that it is a ubiquitous phenomenon, and it may serve as a
      guide for further research.

PMID- 29347127
TI  - Long-time instability in the Runge-Kutta algorithm for a Nose-Hoover heat bath of
      a harmonic chain and its stabilization.
AB  - In this paper, we investigate the Runge-Kutta algorithm for the Nose-Hoover heat
      bath of a harmonic chain. The Runge-Kutta algorithm is found to be unstable in
      long-time calculations, with the system temperature growing exponentially. The
      growth rate increases if time step size is chosen larger. By analyzing the
      Fourier spectra in both space (wave number) and time (frequency), we discover
      that the growth is caused by spurious energy accumulation, particularly at the
      largest wave number. Such accumulation may be explained by von Neumann analysis
      for an infinite chain, with the nonlinear heat bath being ignored. Furthermore,
      we propose to add a filter to remove excessive energy, which effectively
      stabilizes the algorithm.

PMID- 29347128
TI  - Finite-size effect on optimal efficiency of heat engines.
AB  - The optimal efficiency of quantum (or classical) heat engines whose heat baths
      are n-particle systems is given by the strong large deviation. We give the
      optimal work extraction process as a concrete energy-preserving unitary time
      evolution among the heat baths and the work storage. We show that our optimal
      work extraction turns the disordered energy of the heat baths to the ordered
      energy of the work storage, by evaluating the ratio of the entropy difference to
      the energy difference in the heat baths and the work storage, respectively. By
      comparing the statistical mechanical optimal efficiency with the macroscopic
      thermodynamic bound, we evaluate the accuracy of the macroscopic thermodynamics
      with finite-size heat baths from the statistical mechanical viewpoint. We also
      evaluate the quantum coherence effect on the optimal efficiency of the cycle
      processes without restricting their cycle time by comparing the classical and
      quantum optimal efficiencies.

PMID- 29347129
TI  - Boundary-layer effects in droplet splashing.
AB  - A drop falling onto a solid substrate will disintegrate into smaller parts when
      its impact velocity V exceeds the so-called critical velocity for splashing,
      i.e., when V>V^{*}. Under these circumstances, the very thin liquid sheet, which
      is ejected tangentially to the solid after the drop touches the substrate, lifts
      off as a consequence of the aerodynamic forces exerted on it. Subsequently, the
      growth of capillary instabilities breaks the toroidal rim bordering the ejecta
      into smaller droplets, violently ejected radially outward, provoking the splash
      [G. Riboux and J. M. Gordillo, Phys. Rev. Lett. 113, 024507 (2014)]PRLTAO0031
      900710.1103/PhysRevLett.113.024507. In this contribution, the effect of the
      growth of the boundary layer is included in the splash model presented in Phys.
      Rev. Lett. 113, 024507 (2014)PRLTAO0031-900710.1103/PhysRevLett.113.024507,
      obtaining very good agreement between the measured and the predicted values of
      V^{*} for wide ranges of liquid and gas material properties, atmospheric
      pressures, and substrate wettabilities. Our description also modifies the way at
      when the liquid sheet is first ejected, which can now be determined in a much
      more straightforward manner than that proposed in Phys. Rev. Lett. 113, 024507
      (2014)PRLTAO0031-900710.1103/PhysRevLett.113.024507.

PMID- 29347130
TI  - Low-algorithmic-complexity entropy-deceiving graphs.
AB  - In estimating the complexity of objects, in particular, of graphs, it is common
      practice to rely on graph- and information-theoretic measures. Here, using
      integer sequences with properties such as Borel normality, we explain how these
      measures are not independent of the way in which an object, such as a graph, can
      be described or observed. From observations that can reconstruct the same graph
      and are therefore essentially translations of the same description, we see that
      when applying a computable measure such as the Shannon entropy, not only is it
      necessary to preselect a feature of interest where there is one, and to make an
      arbitrary selection where there is not, but also more general properties, such as
      the causal likelihood of a graph as a measure (opposed to randomness), can be
      largely misrepresented by computable measures such as the entropy and entropy
      rate. We introduce recursive and nonrecursive (uncomputable) graphs and graph
      constructions based on these integer sequences, whose different lossless
      descriptions have disparate entropy values, thereby enabling the study and
      exploration of a measure's range of applications and demonstrating the weaknesses
      of computable measures of complexity.

PMID- 29347131
TI  - Minimum energy paths for conformational changes of viral capsids.
AB  - In this work we study conformational changes of viral capsids using techniques of
      large deviations theory for stochastic differential equations. The viral capsid
      is a model of a complex system in which many units-the proteins forming the
      capsomers-interact by weak forces to form a structure with exceptional mechanical
      resistance. The destabilization of such a structure is interesting both, per se,
      since it is related either to infection or maturation processes and because it
      yields insights into the stability of complex structures in which the
      constitutive elements interact by weak attractive forces. We focus here on a
      simplified model of a dodecahedral viral capsid and assume that the capsomers are
      rigid plaquettes with one degree of freedom each. We compute the most probable
      transition path from the closed capsid to the final configuration using minimum
      energy paths and discuss the stability of intermediate states.

PMID- 29347132
TI  - Finite-size scaling in the system of coupled oscillators with heterogeneity in
      coupling strength.
AB  - We consider a mean-field model of coupled phase oscillators with random
      heterogeneity in the coupling strength. The system that we investigate here is a
      minimal model that contains randomness in diverse values of the coupling
      strength, and it is found to return to the original Kuramoto model [Y. Kuramoto,
      Prog. Theor. Phys. Suppl. 79, 223 (1984)10.1143/PTPS.79.223] when the coupling
      heterogeneity disappears. According to one recent paper [H. Hong, H. Chate, L.-H.
      Tang, and H. Park, Phys. Rev. E 92, 022122 (2015)10.1103/PhysRevE.92.022122],
      when the natural frequency of the oscillator in the system is "deterministically"
      chosen, with no randomness in it, the system is found to exhibit the finite-size
      scaling exponent nu[over -]=5/4. Also, the critical exponent for the dynamic
      fluctuation of the order parameter is found to be given by gamma=1/4, which is
      different from the critical exponents for the Kuramoto model with the natural
      frequencies randomly chosen. Originally, the unusual finite-size scaling behavior
      of the Kuramoto model was reported by Hong et al. [H. Hong, H. Chate, H. Park,
      and L.-H. Tang, Phys. Rev. Lett. 99, 184101 (2007)10.1103/PhysRevLett.99.184101],
      where the scaling behavior is found to be characterized by the unusual exponent
      nu[over -]=5/2. On the other hand, if the randomness in the natural frequency is
      removed, it is found that the finite-size scaling behavior is characterized by a
      different exponent, nu[over -]=5/4 [H. Hong, H. Chate, L.-H. Tang, and H. Park,
      Phys. Rev. E 92, 022122 (2015)10.1103/PhysRevE.92.022122]. Those findings brought
      about our curiosity and led us to explore the effects of the randomness on the
      finite-size scaling behavior. In this paper, we pay particular attention to
      investigating the finite-size scaling and dynamic fluctuation when the randomness
      in the coupling strength is considered.

PMID- 29347133
TI  - One-dimensional long-range percolation: A numerical study.
AB  - In this paper we study bond percolation on a one-dimensional chain with power-law
      bond probability C/r^{d+sigma}, where r is the distance length between distinct
      sites and d=1. We introduce and test an order-N Monte Carlo algorithm and we
      determine as a function of sigma the critical value C_{c} at which percolation
      occurs. The critical exponents in the range 0<sigma<1 are reported. Our analysis
      is in agreement, up to a numerical precision ~10^{-3}, with the mean-field result
      for the anomalous dimension eta=2-sigma, showing that there is no correction to
      eta due to correlation effects. The obtained values for C_{c} are compared with a
      known exact bound, while the critical exponent nu is compared with results from
      mean-field theory, from an expansion around the point sigma=1 and from the E
      expansion used with the introduction of a suitably defined effective dimension
      d_{eff} relating the long-range model with a short-range one in dimension
      d_{eff}. We finally present a formulation of our algorithm for bond percolation
      on general graphs, with order N efficiency on a large class of graphs including
      short-range percolation and translationally invariant long-range models in any
      spatial dimension d with sigma>0.

PMID- 29347134
TI  - Dynamics of scroll waves in a cylinder jacket geometry.
AB  - The dynamics of scroll waves in a narrow cylinder jacket-shaped reactor is
      investigated experimentally by optical tomography. The fate of the scroll waves
      of excitation in the Belousov-Zhabotinsky reaction depends on the thickness of
      the cylinder jacket. While at sufficiently wide cylinder jackets vertically
      oriented scroll waves remain stable, the probability that the filament of a
      scroll hits a lateral wall increases as the cylinder jacket narrows. This may
      lead to the rupture of the initial filament and pinning of the filament ends at
      the lateral walls. Filaments that pin to opposite lateral walls shrink and
      reorient to a horizontal orientation; such a reorientation corresponds to a
      transition from an intramural to a transmural scroll wave. The kinetics of the
      reorientation and shrinkage of the scrolls were studied. Furthermore, we find
      that no new filaments were generated upon collision of excitation waves at the
      side of the cylinder jacket opposite to the scroll wave. Thus, under the studied
      conditions, we do not observe any new generation of filaments due to a phenomenon
      like reentry.

PMID- 29347135
TI  - Discrete-time dynamic network model for the spread of susceptible-infective
      recovered diseases.
AB  - We propose a discrete-time dynamic network model describing the spread of
      susceptible-infective-recovered diseases in a population. We consider the case in
      which the nodes in the network change their links due to social mixing dynamics
      as well as in response to the disease. The model shows the behavior that, as we
      increase social mixing, disease spread is inhibited in certain cases, while in
      other cases it is enhanced. We also extend this dynamic network model to take
      into account the case of hidden infection. Here we find that, as expected, the
      disease spreads more readily if there is a time period after contracting the
      disease during which an individual is infective but is not known to have the
      disease.

PMID- 29347136
TI  - Linking initial microstructure and local response during quasistatic granular
      compaction.
AB  - We performed experiments combining three-dimensional x-ray diffraction and x-ray
      computed tomography to explore the relationship between microstructure and local
      force and strain during quasistatic granular compaction. We found that initial
      void space around a grain and contact coordination number before compaction can
      be used to predict regions vulnerable to above-average local force and strain at
      later stages of compaction. We also found correlations between void space around
      a grain and coordination number, and between grain stress and maximum
      interparticle force, at all stages of compaction. Finally, we observed grains
      that fracture to have an above-average initial local void space and a below
      average initial coordination number. Our findings provide (1) a detailed
      description of microstructure evolution during quasistatic granular compaction,
      (2) an approach for identifying regions vulnerable to large values of strain and
      interparticle force, and (3) methods for identifying regions of a material with
      large interparticle forces and coordination numbers from measurements of grain
      stress and local porosity.

PMID- 29347137
TI  - Hyperuniformity of initial conditions and critical decay of a diffusive epidemic
      process belonging to the Manna class.
AB  - For a fixed-energy Manna sandpile model belonging to a Manna class in one
      dimension (d=1), we recently showed that the critical decay is different for
      random and regular initial conditions (ICs). Compared with previous results of
      natural IC for several models, we suggested for the Manna class that the critical
      decay depends on the characteristics of the three ICs. But the dependence on the
      random and regular ICs was shown only for a single model. In this work, we study
      the critical decay for the random and regular ICs for another model of the Manna
      class in d=1, a diffusive epidemic process. It is shown that the critical decay
      exponent agrees with the previous result for each IC, which verifies that IC
      dependence is a common feature of the Manna class. In addition, for the random
      and regular ICs, we measure the variance sigma^{2}(r) of total particle density
      in a region of size r by increasing r up to system size and investigate its
      temporal evolution toward the value sigma_{q}^{2}(r) of the quasisteady state at
      criticality. In d=1,sigma^{2}(r) scales as sigma^{2}(r)~r^{-psi} with psi=1 for
      random distributions and 1<psi<=2 for hyperuniform ones. The temporal evolution
      shows that sigma^{2}(r) of the two ICs differently relax toward sigma_{q}^{2}(r)
      and the regular IC becomes a hyperuniform distribution of psi=2 in the beginning
      of the evolution. We estimate psi=1.45(3) for both the quasisteady state and
      absorbing states, so the quasisteady state is also as hyperuniform as absorbing
      states. The hyperuniformity of the quasisteady state shows that the natural IC
      also should be hyperuniform as much as the quasisteady state, because the natural
      IC is obtained from particle configurations close to the quasisteady state.
      Consequently, the different psi of the three ICs suggest that sigma^{2}(r) can
      classify the characteristics of the three ICs in a unified way and the different
      degree of hyperuniformity of the ICs provides another explanation for the
      observed IC-dependent critical decay in a point of view of initial fluctuations
      and correlations.

PMID- 29347138
TI  - Anomalous diffusion and stress relaxation in surfactant micelles.
AB  - We investigate the mechanisms of anomalous diffusion in cationic surfactant
      micelles using molecular dynamics simulations in the presence of explicit salt
      and solvent-mediated interactions. Simulations show that when the counterion
      density increases, saddle-shaped branched interfaces manifest. In experiments,
      branched structures exhibit lower viscosity as compared to linear and wormlike
      micelles. This has long been attributed to stress relaxation arising from the
      sliding motion of branches along the main chain. Our simulations reveal a
      mechanism of branch motion resulting from an enhanced counterion condensation at
      the branched interfaces and provide quantitative evidence of stress relaxation
      facilitated by branched sliding. Furthermore, depending on the surfactant and
      salt concentrations, which in turn determine the microstructure, we observe
      normal, subdiffusive, and superdiffusive motions of surfactants. Specifically,
      superdiffusive behavior is associated with branch sliding, breakage and
      recombination of micelle fragments, as well as constraint release in entangled
      systems.

PMID- 29347139
TI  - Energy transfer in the nonequilibrium spin-boson model: From weak to strong
      coupling.
AB  - To explore energy transfer in the nonequilibrium spin-boson model (NESB) from
      weak to strong system-bath coupling regimes, we propose a polaron-transformed
      nonequilibrium Green's function (NEGF) method. By combining the polaron
      transformation, we are able to treat the system-bath coupling nonperturbatively,
      thus in direct contrast to conventionally used NEGF methods which take the system
      bath coupling as a perturbation. The Majorana-fermion representation is further
      utilized to evaluate terms in the Dyson series. This method not only allows us to
      deal with weak as well as strong coupling regimes but also enables an
      investigation on the role of bias in the energy transfer. As an application of
      the method, we study an Ohmic NESB. For an unbiased spin system, our energy
      current result smoothly bridges predictions of two benchmarks, namely, the
      quantum master equation and the nonequilibrium noninteracting blip approximation,
      a considerable improvement over existing theories. In case of a biased spin
      system, we found a bias-induced nonmonotonic behavior of the energy conductance
      in the intermediate coupling regime, resulting from the resonant character of the
      energy transfer. This finding may offer a nontrivial quantum control knob over
      energy transfer at the nanoscale.

PMID- 29347140
TI  - Force distribution in a granular medium under dynamic loading.
AB  - Force distribution in a granular medium subjected to an impulse loading is
      investigated in experiment and computer simulations. An experimental technique is
      developed to measure forces acting on individual grains at the bottom of the
      granular sample consisting of steel balls. Discrete element method simulation
      also is performed under conditions mimicking those in experiment. Both theory and
      experiment display exponentially decaying maximum force distributions at the
      bottom of the sample in the range of large forces. In addition, the simulations
      also reveal exponential force distribution throughout the sample and uncover
      correlation properties of the interparticle forces during dynamic loading of the
      granular samples. Simulated time dependence of coordination number, orientational
      order parameter, correlation radius, and force distribution clearly demonstrates
      the nonequilibrium character of the deformation process in a granular medium
      under impulse loading.

PMID- 29347141
TI  - Columnar-disorder phase boundary in a mixture of hard squares and dimers.
AB  - A mixture of hard squares, dimers, and vacancies on a square lattice is known to
      undergo a transition from a low-density disordered phase to a high-density
      columnar ordered phase. Along the fully packed square-dimer line, the system
      undergoes a Kosterliz-Thouless-type transition to a phase with power law
      correlations. We estimate the phase boundary separating the ordered and
      disordered phases by calculating the interfacial tension between two differently
      ordered phases within two different approximation schemes. The analytically
      obtained phase boundary is in good agreement with Monte Carlo simulations.

PMID- 29347142
TI  - Fisher waves: An individual-based stochastic model.
AB  - The propagation of a beneficial mutation in a spatially extended population is
      usually studied using the phenomenological stochastic Fisher-Kolmogorov-Petrovsky
      Piscounov (SFKPP) equation. We derive here an individual-based, stochastic model
      founded on the spatial Moran process where fluctuations are treated exactly. The
      mean-field approximation of this model leads to an equation that is different
      from the phenomenological FKPP equation. At small selection pressure, the front
      behavior can be mapped into a Brownian motion with drift, the properties of which
      can be derived from the microscopic parameters of the Moran model. Finally, we
      generalize the model to take into account dispersal kernels beyond migration to
      nearest neighbors. We show how the effective population size (which controls the
      noise amplitude) and the diffusion coefficient can both be computed from the
      dispersal kernel.

PMID- 29347143
TI  - Time-delayed feedback control of diffusion in random walkers.
AB  - Time delay in general leads to instability in some systems, while specific
      feedback with delay can control fluctuated motion in nonlinear deterministic
      systems to a stable state. In this paper, we consider a stochastic process, i.e.,
      a random walk, and observe its diffusion phenomenon with time-delayed feedback.
      As a result, the diffusion coefficient decreases with increasing delay time. We
      analytically illustrate this suppression of diffusion by using stochastic delay
      differential equations and justify the feasibility of this suppression by
      applying time-delayed feedback to a molecular dynamics model.

PMID- 29347144
TI  - Molecular kinetic analysis of a local equilibrium Carnot cycle.
AB  - We identify a velocity distribution function of ideal gas particles that is
      compatible with the local equilibrium assumption and the fundamental
      thermodynamic relation satisfying the endoreversibility. We find that this
      distribution is a Maxwell-Boltzmann distribution with a spatially uniform
      temperature and a spatially varying local center-of-mass velocity. We construct
      the local equilibrium Carnot cycle of an ideal gas, based on this distribution,
      and show that the efficiency of the present cycle is given by the endoreversible
      Carnot efficiency using the molecular kinetic temperatures of the gas. We also
      obtain an analytic expression of the efficiency at maximum power of our cycle
      under a small temperature difference. Our theory is also confirmed by a molecular
      dynamics simulation.

PMID- 29347145
TI  - Ballistic front dynamics after joining two semi-infinite quantum Ising chains.
AB  - We consider two semi-infinite quantum Ising chains initially at thermal
      equilibrium at two different temperatures and subsequently joined by an
      interaction between their end points. Transport properties such as the heat
      current are determined by the dynamics of the left- and right-moving fermionic
      quasiparticles which characterize the ensuing unitary dynamics. Within the so
      called semiclassical space-time scaling limit we extend known results by
      determining the full space and time dependence of the density and current of
      energy and of fermionic quasiparticles. Upon approaching the edge of the
      propagating front, these quantities as well as the two-point correlation function
      display qualitatively different behaviors depending on the transverse field of
      the chain being critical or not. While in the latter case corrections to the
      leading behavior are described, as expected, by the Airy kernel, in the former a
      novel scaling form emerges with universal features.

PMID- 29347146
TI  - Calculating the rotational friction coefficient of fractal aerosol particles in
      the transition regime using extended Kirkwood-Riseman theory.
AB  - We apply our extended Kirkwood-Riseman theory to compute the translation,
      rotation, and coupling friction tensors and the scalar rotational friction
      coefficient for an aerosol fractal aggregate in the transition flow regime. The
      method can be used for particles consisting of spheres in contact. Our approach
      considers only the linear velocity of the primary spheres in a rotating aggregate
      and ignores rotational and coupling interactions between spheres. We show that
      this simplified approach is within approximately 40% of the true value for any
      particle for Knudsen numbers between 0.01 and 100. The method is especially
      accurate (i.e., within about 5%) near the free-molecule regime, where there is
      little interaction between the particle and the flow field, and for particles
      with low fractal dimension (?2) consisting of many spheres, where the average
      distance between spheres is large and translational interaction effects dominate.
      Our results suggest that there is a universal relationship between the rotational
      friction coefficient and an aggregate Knudsen number, defined as the ratio of
      continuum to free-molecule rotational friction coefficients.

PMID- 29347147
TI  - Generalized run-and-turn motions: From bacteria to Levy walks.
AB  - Swimming bacteria exhibit a repertoire of motility patterns, in which persistent
      motion is interrupted by turning events. What are the statistical properties of
      such random walks? If some particular instances have long been studied, the
      general case where turning times do not follow a Poisson process has remained
      unsolved. We present a generic extension of the continuous time random walks
      formalism relying on operators and noncommutative calculus. The approach is first
      applied to a unimodal model of bacterial motion. We examine the existence of a
      minimum in velocity correlation function and discuss the maximum of diffusivity
      at an optimal value of rotational diffusion. The model is then extended to
      bimodal patterns and includes as particular cases all swimming strategies: run
      and-tumble, run-stop, run-reverse and run-reverse-flick. We characterize their
      velocity correlation functions and investigate how bimodality affects
      diffusivity. Finally, the wider applicability of the method is illustrated by
      considering curved trajectories and Levy walks. Our results are relevant for
      intermittent motion of living beings, be they swimming micro-organisms or
      crawling cells.

PMID- 29347148
TI  - Impact of interaction range and curvature on crystal growth of particles confined
      to spherical surfaces.
AB  - When colloidal particles form a crystal phase on a spherical template, their
      packing is governed by the effective interaction between them and the elastic
      strain of bending the growing crystal. For example, if growth commences under
      appropriate conditions, and the isotropic crystal that forms reaches a critical
      size, growth continues via the incorporation of defects to alleviate elastic
      strain. Recently, it was experimentally found that, if defect formation is
      somehow not possible, the crystal instead continues growing in ribbons that
      protrude from the original crystal. Here we report on computer simulations in
      which we observe both the formation of ribbons at short interaction ranges and
      packings that incorporate defects if the interaction is longer-ranged. The
      ribbons only form above some critical crystal size, below which the nucleus is
      disk-shaped. We find that the scaling of the critical crystal size differs
      slightly from the one proposed in the literature, and we argue that this is
      because the actual morphology transition is caused by the competition between
      line tension and elastic stress, rather than the competition between chemical
      potential and elastic stress.

PMID- 29347149
TI  - Simulation and observation of line-slip structures in columnar structures of soft
      spheres.
AB  - We present the computed phase diagram of columnar structures of soft spheres
      under pressure, of which the main feature is the appearance and disappearance of
      line slips, the shearing of adjacent spirals, as pressure is increased. A
      comparable experimental observation is made on a column of bubbles under forced
      drainage, clearly exhibiting the expected line slip.

PMID- 29347150
TI  - Ashkin-Teller criticality and weak first-order behavior of the phase transition
      to a fourfold degenerate state in two-dimensional frustrated Ising
      antiferromagnets.
AB  - We study the thermal phase transition of the fourfold degenerate phases (the
      plaquette and single-stripe states) in the two-dimensional frustrated Ising model
      on the Shastry-Sutherland lattice using Monte Carlo simulations. The critical
      Ashkin-Teller-like behavior is identified both in the plaquette phase region and
      the single-stripe phase region. The four-state Potts critical end points
      differentiating the continuous transitions from the first-order ones are
      estimated based on finite-size-scaling analyses. Furthermore, a similar behavior
      of the transition to the fourfold single-stripe phase is also observed in the
      anisotropic triangular Ising model. Thus, this work clearly demonstrates that the
      transitions to the fourfold degenerate states of two-dimensional Ising
      antiferromagnets exhibit similar transition behavior.

PMID- 29347151
TI  - Near-field deformation of a liquid interface by atomic force microscopy.
AB  - We experiment the interaction between a liquid puddle and a spherical probe by
      Atomic Force Microscopy (AFM) for a probe radius R ranging from 10 nm to 30 MUm.
      We have developed a new experimental setup by coupling an AFM with a high-speed
      camera and an inverted optical microscope. Interaction force-distance curves (in
      contact mode) and frequency shift-distance curves (in frequency modulation mode)
      are measured for different bulk model liquids for which the probe-liquid Hamaker
      constant H_{pl} is known. The experimental results, analyzed in the frame of the
      theoretical model developed in Phys. Rev. Lett. 108, 106104 (2012)PRLTAO0031
      900710.1103/PhysRevLett.108.106104 and Phys. Rev. E 85, 061602 (2012)PLEEE81539
      375510.1103/PhysRevE.85.061602, allow to determine the "jump-to-contact" critical
      distance d_{min} below which the liquid jumps and wets the probe. Comparison
      between theory and experiments shows that the probe-liquid interaction at
      nanoscale is controlled by the liquid interface deformation. This work shows a
      very good agreement between the theoretical model and the experiments and paves
      the way to experimental studies of liquids at the nanoscale.

PMID- 29347152
TI  - Exact solution of the isotropic majority-vote model on complete graphs.
AB  - The isotropic majority-vote (MV) model, which, apart from the one-dimensional
      case, is thought to be nonequilibrium and violating the detailed balance
      condition. We show that this is not true when the model is defined on a complete
      graph. In the stationary regime, the MV model on a fully connected graph fulfills
      the detailed balance and is equivalent to the modified Ehrenfest urn model. Using
      the master equation approach, we derive the exact expression for the probability
      distribution of finding the system in a given spin configuration. We show that it
      only depends on the absolute value of magnetization. Our theoretical predictions
      are validated by numerical simulations.

PMID- 29347153
TI  - Determination of scale invariance in random-matrix spectral fluctuations without
      unfolding.
AB  - We apply the singular value decomposition (SVD) method, based on normal-mode
      analysis, to decompose the spectra of finite random matrices of standard Gaussian
      ensembles in trend and fluctuation modes. We use the fact that the fluctuation
      modes are scale invariant and follow a power law, to characterize the transition
      between the extreme regular and chaotic cases. Thereby, we quantify the quantum
      chaos in systems described by random matrix theory in a direct way, without
      performing any previous unfolding procedure, and therefore, avoiding possible
      artifacts.

PMID- 29347154
TI  - Ionization-potential depression and dynamical structure factor in dense plasmas.
AB  - The properties of a bound electron system immersed in a plasma environment are
      strongly modified by the surrounding plasma. The modification of an essential
      quantity, the ionization energy, is described by the electronic and ionic self
      energies, including dynamical screening within the framework of the quantum
      statistical theory. Introducing the ionic dynamical structure factor as the
      indicator for the ionic microfield, we demonstrate that ionic correlations and
      fluctuations play a critical role in determining the ionization potential
      depression. This is, in particular, true for mixtures of different ions with
      large mass and charge asymmetry. The ionization potential depression is
      calculated for dense aluminum plasmas as well as for a CH plasma and compared to
      the experimental data and more phenomenological approaches used so far.

PMID- 29347155
TI  - Laser opacity in underdense preplasma of solid targets due to quantum
      electrodynamics effects.
AB  - We investigate how next-generation laser pulses at 10-200PW interact with a solid
      target in the presence of a relativistically underdense preplasma produced by
      amplified spontaneous emission (ASE). Laser hole boring and relativistic
      transparency are strongly restrained due to the generation of electron-positron
      pairs and gamma-ray photons via quantum electrodynamics (QED) processes. A pair
      plasma with a density above the initial preplasma density is formed,
      counteracting the electron-free channel produced by hole boring. This pair
      dominated plasma can block laser transport and trigger an avalanchelike QED
      cascade, efficiently transferring the laser energy to the photons. This renders a
      1-MUm scale-length, underdense preplasma completely opaque to laser pulses at
      this power level. The QED-induced opacity therefore sets much higher contrast
      requirements for such a pulse in solid-target experiments than expected by
      classical plasma physics. Our simulations show, for example, that proton
      acceleration from the rear of a solid with a preplasma would be strongly
      impaired.

PMID- 29347156
TI  - Classification of universality classes for quasideterministic sandpile models.
AB  - The critical behavior of the two-state rotational sandpile model proposed by
      Santra et al. [Phys. Rev. E 75, 041122 (2007)PLEEE81539
      375510.1103/PhysRevE.75.041122] and the locally deterministic and globally
      stochastic three-state sandpile model are investigated via Monte Carlo
      simulations. Through these simulations, we are able to estimate critical
      exponents that characterize the avalanche properties, i.e., the probability
      distributions of the avalanche size, area, lifetime, and gyration radius, and the
      expectation values of the avalanche size and area against time and of the size
      against area. The results are compared with those of the known universality
      classes. The two models are found to yield consistent results within the range of
      statistical error, and appear to be consistent with the stochastic two-state
      Manna sandpile model; therefore, both models appear to belong to the Manna
      universality class. Our results contradict the earlier conclusion of Santra et
      al., which we attribute to the slow convergence of the probability distribution
      to the asymptotic power-law behavior, particularly for the size and lifetime of
      avalanches.

PMID- 29347157
TI  - Finite-time generalization of the thermodynamic uncertainty relation.
AB  - For fluctuating currents in nonequilibrium steady states, the recently discovered
      thermodynamic uncertainty relation expresses a fundamental relation between their
      variance and the overall entropic cost associated with the driving. We show that
      this relation holds not only for the long-time limit of fluctuations, as
      described by large deviation theory, but also for fluctuations on arbitrary
      finite time scales. This generalization facilitates applying the thermodynamic
      uncertainty relation to single molecule experiments, for which infinite time
      scales are not accessible. Importantly, often this finite-time variant of the
      relation allows inferring a bound on the entropy production that is even stronger
      than the one obtained from the long-time limit. We illustrate the relation for
      the fluctuating work that is performed by a stochastically switching laser
      tweezer on a trapped colloidal particle.

PMID- 29347158
TI  - Modification of magnetohydrodynamic waves by the relativistic Hall effect.
AB  - This study shows that a relativistic Hall effect significantly changes the
      properties of wave propagation by deriving a linear dispersion relation for
      relativistic Hall magnetohydrodynamics (HMHD). Whereas, in nonrelativistic HMHD,
      the phase and group velocities of fast magnetosonic wave become anisotropic with
      an increasing Hall effect, the relativistic Hall effect brings upper bounds to
      the anisotropies. The Alfven wave group velocity with strong Hall effect also
      becomes less anisotropic than the nonrelativistic case. Moreover, the group
      velocity surfaces of Alfven and fast waves coalesce into a single surface in the
      direction other than near perpendicular to the ambient magnetic field. It is also
      remarkable that a characteristic scale length of the relativistic HMHD depends on
      ion temperature, magnetic field strength, and density while the nonrelativistic
      HMHD scale length, i.e., ion skin depth, depends only on density. The modified
      characteristic scale length increases as the ion temperature increases and
      decreases as the magnetic field strength increases.

PMID- 29347159
TI  - Thermodynamic dislocation theory of high-temperature deformation in aluminum and
      steel.
AB  - The statistical-thermodynamic dislocation theory developed in previous papers is
      used here in an analysis of high-temperature deformation of aluminum and steel.
      Using physics-based parameters that we expect theoretically to be independent of
      strain rate and temperature, we are able to fit experimental stress-strain curves
      for three different strain rates and three different temperatures for each of
      these two materials. Our theoretical curves include yielding transitions at zero
      strain in agreement with experiment. We find that thermal softening effects are
      important even at the lowest temperatures and smallest strain rates.

PMID- 29347160
TI  - Markov chain sampling of the O(n) loop models on the infinite plane.
AB  - A numerical method was recently proposed in Herdeiro and Doyon [Phys. Rev. E 94,
      043322 (2016)10.1103/PhysRevE.94.043322] showing a precise sampling of the
      infinite plane two-dimensional critical Ising model for finite lattice
      subsections. The present note extends the method to a larger class of models,
      namely the O(n) loop gas models for n?(1,2]. We argue that even though the Gibbs
      measure is nonlocal, it is factorizable on finite subsections when sufficient
      information on the loops touching the boundaries is stored. Our results attempt
      to show that provided an efficient Markov chain mixing algorithm and an improved
      discrete lattice dilation procedure the planar limit of the O(n) models can be
      numerically studied with efficiency similar to the Ising case. This confirms that
      scale invariance is the only requirement for the present numerical method to
      work.

PMID- 29347161
TI  - Colloidal dynamics over a tilted periodic potential: Forward and reverse
      transition probabilities and entropy production in a nonequilibrium steady state.
AB  - We report a systematic study of the forward and reverse transition probability
      density functions (TPDFs) and entropy production in a nonequilibrium steady state
      (NESS). The NESS is realized in a two-layer colloidal system, in which the bottom
      layer colloidal crystal provides a two-dimensional periodic potential U_{0}(x,y)
      for the top-layer diffusing particles. By tilting the sample at an angle with
      respect to gravity, a tangential component of the gravitational force F is
      applied to the diffusing particles, which breaks the detailed balance (DB)
      condition and generates a steady particle flux along the [1,0] crystalline
      orientation. While both the measured forward and reverse TPDFs reveal interesting
      space-time dependence, their ratio is found to be independent of time and obeys a
      DB-like relation. The experimental results are in good agreement with the
      theoretical predictions. This study thus provides a better understanding on how
      entropy is generated and heat is dissipated to the reservoir during a NESS
      transition process. It also demonstrates the applications of the two-layer
      colloidal system in the study of NESS transition dynamics.

PMID- 29347162
TI  - Scaling properties of multilayer random networks.
AB  - Multilayer networks are widespread in natural and manmade systems. Key properties
      of these networks are their spectral and eigenfunction characteristics, as they
      determine the critical properties of many dynamics occurring on top of them.
      Here, we numerically demonstrate that the normalized localization length beta of
      the eigenfunctions of multilayer random networks follows a simple scaling law
      given by beta=x^{*}/(1+x^{*}), with x^{*}=gamma(b_{eff}^{2}/L)^{delta}, delta~1,
      and b_{eff} being the effective bandwidth of the adjacency matrix of the network,
      whose size is L. The scaling law for beta, that we validate on real-world
      networks, might help to better understand criticality in multilayer networks and
      to predict the eigenfunction localization properties of them.

PMID- 29347163
TI  - Pendular behavior of public transport networks.
AB  - In this paper, we propose a methodology that bears close resemblance to the
      Fourier analysis of the first harmonic to study networks subjected to pendular
      behavior. In this context, pendular behavior is characterized by the phenomenon
      of people's dislocation from their homes to work in the morning and people's
      dislocation in the opposite direction in the afternoon. Pendular behavior is a
      relevant phenomenon that takes place in public transport networks because it may
      reduce the overall efficiency of the system as a result of the asymmetric
      utilization of the system in different directions. We apply this methodology to
      the bus transport system of Brasilia, which is a city that has commercial and
      residential activities in distinct boroughs. We show that this methodology can be
      used to characterize the pendular behavior of this system, identifying the most
      critical nodes and times of the day when this system is in more severe demanded.

PMID- 29347164
TI  - Observation of a strong-coupling effect on electron-ion collisions in ultracold
      plasmas.
AB  - Ultracold plasmas (UCPs) provide a well-controlled system for studying multiple
      aspects in plasma physics that include collisions and strong-coupling effects. By
      applying a short electric field pulse to an UCP, a plasma electron center-of-mass
      oscillation can be initiated. For accessible parameter ranges, the damping rate
      of this oscillation is determined by the electron-ion collision rate. We
      performed measurements of the oscillation damping rate with such parameters and
      compared the measured rates to both a molecular dynamics (MD) simulation that
      includes strong-coupling effects and a Monte Carlo binary collision simulation
      designed to predict the damping rate including only weak-coupling considerations.
      We found agreement between the experimentally measured damping rate and the MD
      result. This agreement did require including the influence of a previously
      unreported UCP heating mechanism whereby the presence of a dc electric field
      during ionization increased the electron temperature, but estimations and
      simulations indicate that such a heating mechanism should be present for our
      parameters. The measured damping rate at our coldest electron temperature
      conditions was much faster than the weak-coupling prediction obtained from the
      Monte Carlo binary collision simulation, which indicates the presence of a
      significant strong-coupling influence. The density averaged electron strong
      coupling parameter Gamma measured at our coldest electron temperature conditions
      was 0.35(8).

PMID- 29347165
TI  - Interaction between a tubular beam of charged particles and a dispersive
      metamaterial of cylindrical configuration.
AB  - The interaction between a tubular beam of charged particles and a dispersive
      metamaterial of cylindrical configuration has been investigated theoretically.
      This metamaterial may have negative permittivity and negative permeability
      simultaneously over a certain frequency range where it behaves like a left-handed
      metamaterial. The dispersion equation for the eigenmodes spectra of a
      metamaterial and the coupled modes spectra of the system have been derived and
      numerically analyzed. It has been found that the absolute beam instability of
      bulk-surface waves occurs because of peculiarities of the eigenmodes spectra of a
      left-handed metamaterial. Specifically, the resonant frequency behavior of the
      permeability causes the emergence of the sections of dispersion curves with
      anomalous dispersion. It has been demonstrated that the symmetric bulk-surface
      mode with two field variations along the cylinder radius possesses the maximum
      value of instability increment. The obtained results allow us to propose the left
      handed metamaterial as the delaying medium in oscillators of electromagnetic
      radiation without a need to provide an additional feedback in the system just as
      in a backward-wave tube.

PMID- 29347166
TI  - Solution to urn models of pairwise interaction with application to social,
      physical, and biological sciences.
AB  - We investigate a family of urn models that correspond to one-dimensional random
      walks with quadratic transition probabilities that have highly diverse
      applications. Well-known instances of these two-urn models are the Ehrenfest
      model of molecular diffusion, the voter model of social influence, and the Moran
      model of population genetics. We also provide a generating function method for
      diagonalizing the corresponding transition matrix that is valid if and only if
      the underlying mean density satisfies a linear differential equation and express
      the eigenvector components as terms of ordinary hypergeometric functions. The
      nature of the models lead to a natural extension to interaction between agents in
      a general network topology. We analyze the dynamics on uncorrelated heterogeneous
      degree sequence networks and relate the convergence times to the moments of the
      degree sequences for various pairwise interaction mechanisms.

PMID- 29347167
TI  - How fast does a random walk cover a torus?
AB  - We present high statistics simulation data for the average time <T_{cover}(L)>
      that a random walk needs to cover completely a two-dimensional torus of size L*L.
      They confirm the mathematical prediction that <T_{cover}(L)>~(LlnL)^{2} for large
      L, but the prefactor seems to deviate significantly from the supposedly exact
      result 4/pi derived by Dembo et al. [Ann. Math. 160, 433 (2004)ANMAAH0003
      486X10.4007/annals.2004.160.433], if the most straightforward extrapolation is
      used. On the other hand, we find that this scaling does hold for the time
      T_{N(t)=1}(L) at which the average number of yet unvisited sites is 1, as also
      predicted previously. This might suggest (wrongly) that <T_{cover}(L)> and
      T_{N(t)=1}(L) scale differently, although the distribution of rescaled cover
      times becomes sharp in the limit L->infinity. But our results can be reconciled
      with those of Dembo et al. by a very slow and nonmonotonic convergence of
      <T_{cover}(L)>/(LlnL)^{2}, as had been indeed proven by Belius et al. [Probab.
      Theory Relat. Fields 167, 461 (2017)10.1007/s00440-015-0689-6] for Brownian
      walks, and was conjectured by them to hold also for lattice walks.

PMID- 29347168
TI  - Quantifying the entropic cost of cellular growth control.
AB  - Viewing the ways a living cell can organize its metabolism as the phase space of
      a physical system, regulation can be seen as the ability to reduce the entropy of
      that space by selecting specific cellular configurations that are, in some sense,
      optimal. Here we quantify the amount of regulation required to control a cell's
      growth rate by a maximum-entropy approach to the space of underlying metabolic
      phenotypes, where a configuration corresponds to a metabolic flux pattern as
      described by genome-scale models. We link the mean growth rate achieved by a
      population of cells to the minimal amount of metabolic regulation needed to
      achieve it through a phase diagram that highlights how growth suppression can be
      as costly (in regulatory terms) as growth enhancement. Moreover, we provide an
      interpretation of the inverse temperature beta controlling maximum-entropy
      distributions based on the underlying growth dynamics. Specifically, we show that
      the asymptotic value of beta for a cell population can be expected to depend on
      (i) the carrying capacity of the environment, (ii) the initial size of the
      colony, and (iii) the probability distribution from which the inoculum was
      sampled. Results obtained for E. coli and human cells are found to be remarkably
      consistent with empirical evidence.

PMID- 29347169
TI  - Nonlinear mechanics of rigidifying curves.
AB  - Thin shells are characterized by a high cost of stretching compared to bending.
      As a result isometries of the midsurface of a shell play a crucial role in their
      mechanics. In turn, curves on the midsurface with zero normal curvature play a
      critical role in determining the number and behavior of isometries. In this
      paper, we show how the presence of these curves results in a decrease in the
      number of linear isometries. Paradoxically, shells are also known to continuously
      fold more easily across these rigidifying curves than other curves on the
      surface. We show how including nonlinearities in the strain can explain these
      phenomena and demonstrate folding isometries with explicit solutions to the
      nonlinear isometry equations. In addition to explicit solutions, exact geometric
      arguments are given to validate and guide our analysis in a coordinate-free way.

PMID- 29347170
TI  - Information propagation in a noisy gene cascade.
AB  - We use information theory to study the information transmission through a simple
      gene cascade where the product of an unregulated gene regulates the expression
      activity of a cooperative genetic switch. While the input signal is provided by
      the upstream gene with two states, we consider that the expression of downstream
      gene is controlled by a cis-regulatory system with three binding sites for the
      regulator product, which can bind cooperatively. By computing exactly the
      associated probability distributions, we estimate information transmission
      thought the mutual information measure. We found that the mutual information
      associated with unimodal input signal is lower than the associated with bimodal
      inputs. We also observe that mutual information presents a maximum in the
      cooperativity intensity, and the position of this maximum depends on the kinetic
      rates of the promoter. Furthermore, we found that the bursting dynamics of the
      input signal can enhance the information transmission capacity.

PMID- 29347171
TI  - Properties and relative measure for quantifying quantum synchronization.
AB  - Although quantum synchronization phenomena and corresponding measures have been
      widely discussed recently, it is still an open question how to characterize
      directly the influence of nonlocal correlation, which is the key distinction for
      identifying classical and quantum synchronizations. In this paper, we present
      basic postulates for quantifying quantum synchronization based on the related
      theory in Mari's work [Phys. Rev. Lett. 111, 103605 (2013)PRLTAO0031
      900710.1103/PhysRevLett.111.103605], and we give a general formula of a quantum
      synchronization measure with clear physical interpretations. By introducing
      Pearson's parameter, we show that the obvious characteristics of our measure are
      the relativity and monotonicity. As an example, the measure is applied to
      describe synchronization among quantum optomechanical systems under a Markovian
      bath. We also show the potential by quantifying generalized synchronization and
      discrete variable synchronization with this measure.

PMID- 29347172
TI  - Dynamic finite-size scaling at first-order transitions.
AB  - We investigate the dynamic behavior of finite-size systems close to a first-order
      transition (FOT). We develop a dynamic finite-size scaling (DFSS) theory for the
      dynamic behavior in the coexistence region where different phases coexist. This
      is characterized by an exponentially large time scale related to the tunneling
      between the two phases. We show that, when considering time scales of the order
      of the tunneling time, the dynamic behavior can be described by a two-state
      coarse-grained dynamics. This allows us to obtain exact predictions for the
      dynamical scaling functions. To test the general DFSS theory at FOTs, we consider
      the two-dimensional Ising model in the low-temperature phase, where the external
      magnetic field drives a FOT, and the 20-state Potts model, which undergoes a
      thermal FOT. Numerical results for a purely relaxational dynamics fully confirm
      the general theory.

PMID- 29347173
TI  - Hybrid colored noise process with space-dependent switching rates.
AB  - A fundamental issue in the theory of continuous stochastic process is the
      interpretation of multiplicative white noise, which is often referred to as the
      Ito-Stratonovich dilemma. From a physical perspective, this reflects the need to
      introduce additional constraints in order to specify the nature of the noise,
      whereas from a mathematical perspective it reflects an ambiguity in the
      formulation of stochastic differential equations (SDEs). Recently, we have
      identified a mechanism for obtaining an Ito SDE based on a form of temporal
      disorder. Motivated by switching processes in molecular biology, we considered a
      Brownian particle that randomly switches between two distinct conformational
      states with different diffusivities. In each state, the particle undergoes normal
      diffusion (additive noise) so there is no ambiguity in the interpretation of the
      noise. However, if the switching rates depend on position, then in the fast
      switching limit one obtains Brownian motion with a space-dependent diffusivity of
      the Ito form. In this paper, we extend our theory to include colored additive
      noise. We show that the nature of the effective multiplicative noise process
      obtained by taking both the white-noise limit (kappa->0) and fast switching limit
      (epsilon->0) depends on the order the two limits are taken. If the white-noise
      limit is taken first, then we obtain Ito, and if the fast switching limit is
      taken first, then we obtain Stratonovich. Moreover, the form of the effective
      diffusion coefficient differs in the two cases. The latter result holds even in
      the case of space-independent transition rates, where one obtains additive noise
      processes with different diffusion coefficients. Finally, we show that yet
      another form of multiplicative noise is obtained in the simultaneous limit
      epsilon,kappa->0 with epsilon/kappa^{2} fixed.

PMID- 29347174
TI  - Periodic jetting and monodisperse jet drops from oblique gas injection.
AB  - When air is blown in a straw or tube near an air-liquid interface, typically one
      of two behaviors is observed: a dimple in the liquid's surface, or a frenzy of
      sputtering bubbles, waves, and spray. Here we report and characterize an
      intermediate regime that can develop when a confined air jet enters the interface
      at an angle. This regime is oscillatory with a distinct characteristic frequency
      and can develop periodic angled jets that can break up into monodisperse
      aerosols. The underlying mechanisms responsible for this highly periodic regime
      are not well understood. Here we flow a continuous stream of gas through a tube
      near a liquid surface, observing both optically and acoustically the deformation
      of the liquid-air interface as various parameters are systematically adjusted. We
      show that the Kelvin-Helmholtz instability is responsible for the inception of
      waves within a cavity formed by the gas. Inertia, gravity, and capillary forces
      both shape the cavity and govern the frequency and amplitude of these gas-induced
      cavity waves. The flapping cavity focuses the waves into a series of periodic
      jets that can break up into droplets following the Rayleigh-Plateau instability.
      We present scaling arguments to rationalize the fundamental frequencies driving
      this system, as well as the conditions that bound the periodic regime. These
      frequencies and conditions compare well with our experimental results.

PMID- 29347175
TI  - Publisher's Note: Asymmetric transmission of sound wave in cavitating liquids
      [Phys. Rev. E 95, 033118 (2017)].
AB  - This corrects the article DOI: 10.1103/PhysRevE.95.033118.

PMID- 29347176
TI  - Optimal allocation of resources for suppressing epidemic spreading on networks.
AB  - Efficient allocation of limited medical resources is crucial for controlling
      epidemic spreading on networks. Based on the susceptible-infected-susceptible
      model, we solve the optimization problem of how best to allocate the limited
      resources so as to minimize prevalence, providing that the curing rate of each
      node is positively correlated to its medical resource. By quenched mean-field
      theory and heterogeneous mean-field (HMF) theory, we prove that an epidemic
      outbreak will be suppressed to the greatest extent if the curing rate of each
      node is directly proportional to its degree, under which the effective infection
      rate lambda has a maximal threshold lambda_{c}^{opt}=1/<k>, where <k> is the
      average degree of the underlying network. For a weak infection region
      (lambda?lambda_{c}^{opt}), we combine perturbation theory with the Lagrange
      multiplier method (LMM) to derive the analytical expression of optimal allocation
      of the curing rates and the corresponding minimized prevalence. For a general
      infection region (lambda>lambda_{c}^{opt}), the high-dimensional optimization
      problem is converted into numerically solving low-dimensional nonlinear equations
      by the HMF theory and LMM. Counterintuitively, in the strong infection region the
      low-degree nodes should be allocated more medical resources than the high-degree
      nodes to minimize prevalence. Finally, we use simulated annealing to validate the
      theoretical results.

PMID- 29347177
TI  - Theory of helicoids and skyrmions in confined cholesteric liquid crystals.
AB  - Cholesteric liquid crystals experience geometric frustration when they are
      confined between surfaces with anchoring conditions that are incompatible with
      the cholesteric twist. Because of this frustration, they develop complex
      topological defect structures, which may be helicoids or skyrmions. We develop a
      theory for these structures, which extends previous theoretical research by
      deriving exact solutions for helicoids with the assumption of constant azimuth,
      calculating numerical solutions for helicoids and skyrmions with varying azimuth,
      and interpreting the results in terms of competition between terms in the free
      energy.

PMID- 29347178
TI  - Stability of the fluid interface in a Hele-Shaw cell subjected to horizontal
      vibrations.
AB  - The stability of the horizontal interface of two immiscible viscous fluids in a
      Hele-Shaw cell subject to gravity and horizontal vibrations is studied. The
      problem is reduced to the generalized Hill equation, which is solved analytically
      by the multiple scale method and numerically. The long-wave instability, the
      resonance (parametric resonance) excitation of waves at finite frequencies of
      vibrations (for the first three resonances), and the limit of high-frequency
      vibrations are studied analytically under the assumption of small amplitudes of
      vibrations and small viscosity. For finite amplitudes of vibrations, finite wave
      numbers, and finite viscosity, the study is performed numerically. The influence
      of the specific natural control parameters and physical parameters of the system
      on its instability threshold is discussed. The results provide extension to other
      results [J. Bouchgl, S. Aniss, and M. Souhar, Phys. Rev. E 88, 023027
      (2013)10.1103/PhysRevE.88.023027], where the authors considered a similar problem
      but took into account viscosity in the basic state and did not consider it in the
      equations for perturbations.

PMID- 29347179
TI  - Classical ergodicity and quantum eigenstate thermalization: Analysis in fully
      connected Ising ferromagnets.
AB  - We investigate the relation between the classical ergodicity and the quantum
      eigenstate thermalization in the fully connected Ising ferromagnets. In the case
      of spin-1/2, an expectation value of an observable in a single-energy eigenstate
      coincides with the long-time average in the underlying classical dynamics, which
      is a consequence of the Wentzel-Kramers-Brillouin approximation. In the case of
      spin-1, the underlying classical dynamics is not necessarily ergodic. In that
      case, it turns out that, in the thermodynamic limit, the statistics of the
      expectation values of an observable in the energy eigenstates coincides with the
      statistics of the long-time averages in the underlying classical dynamics
      starting from random initial states sampled uniformly from the classical phase
      space. This feature seems to be a general property in semiclassical systems, and
      the result presented here is crucial in discussing equilibration, thermalization,
      and dynamical transitions of such systems.

PMID- 29347180
TI  - Lattice Boltzmann modeling and simulation of liquid jet breakup.
AB  - A three-dimensional color-fluid lattice Boltzmann model for immiscible two-phase
      flows is developed in the framework of a three-dimensional 27-velocity (D3Q27)
      lattice. The collision operator comprises the D3Q27 versions of three
      suboperators: a multiple-relaxation-time (MRT) collision operator, a generalized
      Liu-Valocchi-Kang perturbation operator, and a Latva-Kokko-Rothman recoloring
      operator. A D3Q27 version of an enhanced equilibrium distribution function is
      also incorporated into this model to improve the Galilean invariance. Three types
      of numerical tests, namely, a static droplet, an oscillating droplet, and the
      Rayleigh-Taylor instability, show a good agreement with analytical solutions and
      numerical simulations. Following these numerical tests, this model is applied to
      liquid-jet-breakup simulations. The simulation conditions are matched to the
      conditions of the previous experiments. In this case, numerical stability is
      maintained throughout the simulation, although the kinematic viscosity for the
      continuous phase is set as low as 1.8*10^{-4}, in which case the corresponding
      Reynolds number is 3.4*10^{3}; the developed lattice Boltzmann model based on the
      D3Q27 lattice enables us to perform the simulation with parameters directly
      matched to the experiments. The jet's liquid column transitions from an
      asymmetrical to an axisymmetrical shape, and entrainment occurs from the side of
      the jet. The measured time history of the jet's leading-edge position shows a
      good agreement with the experiments. Finally, the reproducibility of the regime
      map for liquid-liquid systems is assessed. The present lattice Boltzmann
      simulations well reproduce the characteristics of predicted regimes, including
      varicose breakup, sinuous breakup, and atomization.

PMID- 29347181
TI  - Relationship between the size of a camphor-driven rotor and its angular velocity.
AB  - We consider a rotor made of two camphor disks glued below the ends of a plastic
      stripe. The disks are floating on a water surface and the plastic stripe does not
      touch the surface. The system can rotate around a vertical axis located at the
      center of the stripe. The disks dissipate camphor molecules. The driving momentum
      comes from the nonuniformity of surface tension resulting from inhomogeneous
      surface concentration of camphor molecules around the disks. We investigate the
      stationary angular velocity as a function of rotor radius l. For large l the
      angular velocity decreases for increasing l. At a specific value of l the angular
      velocity reaches its maximum and, for short l it rapidly decreases. Such behavior
      is confirmed by a simple numerical model. The model also predicts that there is a
      critical rotor size below which it does not rotate. Within the introduced model
      we analyze the type of this bifurcation.

PMID- 29347182
TI  - Propulsion via flexible flapping in granular media.
AB  - Biological locomotion in nature is often achieved by the interaction between a
      flexible body and its surrounding medium. The interaction of a flexible body with
      granular media is less understood compared with viscous fluids partially due to
      its complex rheological properties. In this work, we explore the effect of
      flexibility on granular propulsion by considering a simple mechanical model in
      which a rigid rod is connected to a torsional spring that is under a displacement
      actuation using a granular resistive force theory. Through a combined numerical
      and asymptotic investigation, we characterize the propulsive dynamics of such a
      flexible flapper in relation to the actuation amplitude and spring stiffness, and
      we compare these dynamics with those observed in a viscous fluid. In addition, we
      demonstrate that the maximum possible propulsive force can be obtained in the
      steady propulsion limit with a finite spring stiffness and large actuation
      amplitude. These results may apply to the development of synthetic locomotive
      systems that exploit flexibility to move through complex terrestrial media.

PMID- 29347183
TI  - Quantum dynamics of long-range interacting systems using the positive-P and gauge
      P representations.
AB  - We provide the necessary framework for carrying out stochastic positive-P and
      gauge-P simulations of bosonic systems with long-range interactions. In these
      approaches, the quantum evolution is sampled by trajectories in phase space,
      allowing calculation of correlations without truncation of the Hilbert space or
      other approximations to the quantum state. The main drawback is that the
      simulation time is limited by noise arising from interactions. We show that the
      long-range character of these interactions does not further increase the
      limitations of these methods, in contrast to the situation for alternatives such
      as the density matrix renormalization group. Furthermore, stochastic gauge
      techniques can also successfully extend simulation times in the long-range
      interaction case, by making using of parameters that affect the noise properties
      of trajectories, without affecting physical observables. We derive essential
      results that significantly aid the use of these methods: estimates of the
      available simulation time, optimized stochastic gauges, a general form of the
      characteristic stochastic variance, and adaptations for very large systems.
      Testing the performance of particular drift and diffusion gauges for nonlocal
      interactions, we find that, for small to medium systems, drift gauges are
      beneficial, whereas for sufficiently large systems, it is optimal to use only a
      diffusion gauge. The methods are illustrated with direct numerical simulations of
      interaction quenches in extended Bose-Hubbard lattice systems and the excitation
      of Rydberg states in a Bose-Einstein condensate, also without the need for the
      typical frozen gas approximation. We demonstrate that gauges can indeed lengthen
      the useful simulation time.

PMID- 29347184
TI  - Boundary in the dynamic phase of globally coupled oscillatory and excitable
      units.
AB  - There is a crucial boundary between dynamic phase 1 and dynamic phase 2 of
      globally coupled oscillatory and excitable units, where the mean field is
      constant and oscillates in the former and the latter, respectively. This boundary
      is theoretically derived here for a large population of dynamical units, each
      having only a phase variable, where it is assumed that both the coupling strength
      and the distribution width of bifurcation parameters are equally small. This
      theory, which is applicable only if all or most of the units are intrinsically
      oscillatory, is confirmed to agree with simulation results for two different
      distribution densities.

PMID- 29347185
TI  - Balancing specificity, sensitivity, and speed of ligand discrimination by zero
      order ultraspecificity.
AB  - Specific interactions between receptors and their target ligands in the presence
      of nontarget ligands are crucial for biological processes such as T cell ligand
      discrimination. To discriminate between the target and nontarget ligands, cells
      have to increase specificity to the target ligands by amplifying the small
      differences in affinity among ligands. In addition, sensitivity to the ligand
      concentration and quick discrimination are also important to detect low amounts
      of target ligands and facilitate fast cellular decision making after ligand
      recognition. In this work we propose a mechanism for nonlinear specificity
      amplification (ultraspecificity) based on zero-order saturating reactions, which
      was originally proposed to explain nonlinear sensitivity amplification
      (ultrasensitivity) to the ligand concentration. In contrast to the previously
      proposed proofreading mechanisms that amplify the specificity by a multistep
      reaction, our model can produce an optimal balance of specificity, sensitivity,
      and quick discrimination. Furthermore, we show that a model for insensitivity to
      a large number of nontarget ligands can be naturally derived from a model with
      the zero-order ultraspecificity. The zero-order ultraspecificity, therefore, may
      provide an alternative way to understand ligand discrimination from the viewpoint
      of nonlinear properties in biochemical reactions.

PMID- 29347186
TI  - Extreme event statistics in a drifting Markov chain.
AB  - We analyze extreme event statistics of experimentally realized Markov chains with
      various drifts. Our Markov chains are individual trajectories of a single atom
      diffusing in a one-dimensional periodic potential. Based on more than 500
      individual atomic traces we verify the applicability of the Sparre Andersen
      theorem to our system despite the presence of a drift. We present detailed
      analysis of four different rare-event statistics for our system: the
      distributions of extreme values, of record values, of extreme value occurrence in
      the chain, and of the number of records in the chain. We observe that, for our
      data, the shape of the extreme event distributions is dominated by the underlying
      exponential distance distribution extracted from the atomic traces. Furthermore,
      we find that even small drifts influence the statistics of extreme events and
      record values, which is supported by numerical simulations, and we identify cases
      in which the drift can be determined without information about the underlying
      random variable distributions. Our results facilitate the use of extreme event
      statistics as a signal for small drifts in correlated trajectories.

PMID- 29347187
TI  - Mean-field dynamics of a population of stochastic map neurons.
AB  - We analyze the emergent regimes and the stimulus-response relationship of a
      population of noisy map neurons by means of a mean-field model, derived within
      the framework of cumulant approach complemented by the Gaussian closure
      hypothesis. It is demonstrated that the mean-field model can qualitatively
      account for stability and bifurcations of the exact system, capturing all the
      generic forms of collective behavior, including macroscopic excitability,
      subthreshold oscillations, periodic or chaotic spiking, and chaotic bursting
      dynamics. Apart from qualitative analogies, we find a substantial quantitative
      agreement between the exact and the approximate system, as reflected in matching
      of the parameter domains admitting the different dynamical regimes, as well as
      the characteristic properties of the associated time series. The effective model
      is further shown to reproduce with sufficient accuracy the phase response curves
      of the exact system and the assembly's response to external stimulation of finite
      amplitude and duration.

PMID- 29347188
TI  - Reply to "Comment on 'Flow of wet granular materials: A numerical study' ".
AB  - In his Comment on our paper [Phys. Rev. E 92, 022201
      (2015)10.1103/PhysRevE.92.022201], Chareyre criticizes, as inaccurate, the simple
      approach we adopted to explain the strong enhancement of the quasistatic shear
      strength of the material caused by capillary cohesion. He also observes that a
      similar form of the "effective stress" approach, accounting for the capillary
      shear stress, which we neglected, results in a quantitatively correct prediction
      of this yield stress. We agree with these remarks, which we deem quite relevant
      and valuable. We nevertheless point out that the initial approximation, despite
      ~25% errors on shear strength in the worst cases, provides a convenient estimate
      of the Mohr-Coulomb cohesion of the material, which is directly related to the
      coordination number. We argue that the effective stress assumption, despite its
      surprising success in the range of states explored in Khamseh et al. [Phys. Rev.
      E 92, 022201 (2015)10.1103/PhysRevE.92.022201], is bound to fail in strongly
      cohesion-dominated material states.

PMID- 29347189
TI  - Turing mechanism for homeostatic control of synaptic density during C. elegans
      growth.
AB  - We propose a mechanism for the homeostatic control of synapses along the ventral
      cord of Caenorhabditis elegans during development, based on a form of Turing
      pattern formation on a growing domain. C. elegans is an important animal model
      for understanding cellular mechanisms underlying learning and memory. Our
      mathematical model consists of two interacting chemical species, where one is
      passively diffusing and the other is actively trafficked by molecular motors,
      which switch between forward and backward moving states (bidirectional
      transport). This differs significantly from the standard mechanism for Turing
      pattern formation based on the interaction between fast and slow diffusing
      species. We derive evolution equations for the chemical concentrations on a
      slowly growing one-dimensional domain, and use numerical simulations to
      demonstrate the insertion of new concentration peaks as the length increases.
      Taking the passive component to be the protein kinase CaMKII and the active
      component to be the glutamate receptor GLR-1, we interpret the concentration
      peaks as sites of new synapses along the length of C. elegans, and thus show how
      the density of synaptic sites can be maintained.

PMID- 29347190
TI  - Exact phase boundaries and topological phase transitions of the XYZ spin chain.
AB  - Within the block spin renormalization group, we give a very simple derivation of
      the exact phase boundaries of the XYZ spin chain. First, we identify the Ising
      order along x[over ] or y[over ] as attractive renormalization group fixed points
      of the Kitaev chain. Then, in a global phase space composed of the anisotropy
      lambda of the XY interaction and the coupling Delta of the
      Deltasigma^{z}sigma^{z} interaction, we find that the above fixed points remain
      attractive in the two-dimesional parameter space. We therefore classify the
      gapped phases of the XYZ spin chain as: (1) either attracted to the Ising limit
      of the Kitaev-chain, which in turn is characterized by winding number +/-1,
      depending on whether the Ising order parameter is along x[over ] or y[over ]
      directions; or (2) attracted to the charge density wave (CDW) phases of the
      underlying Jordan-Wigner fermions, which is characterized by zero winding number.
      We therefore establish that the exact phase boundaries of the XYZ model in
      Baxter's solution indeed correspond to topological phase transitions. The
      topological nature of the phase transitions of the XYZ model justifies why our
      analytical solution of the three-site problem that is at the core of the present
      renormalization group treatment is able to produce the exact phase boundaries of
      Baxter's solution. We argue that the distribution of the winding numbers between
      the three Ising phases is a matter of choice of the coordinate system, and
      therefore the CDW-Ising phase is entitled to host appropriate form of zero modes.
      We further observe that in the Kitaev-chain the renormalization group flow can be
      cast into a geometric progression of a properly identified parameter. We show
      that this new parameter is actually the size of the (Majorana) zero modes.

PMID- 29347191
TI  - Time-reversal symmetry for systems in a constant external magnetic field.
AB  - The time-reversal properties of charged systems in a constant external magnetic
      field are reconsidered in this paper. We show that the evolution equations of the
      system are invariant under a new symmetry operation that implies a new signature
      property for time-correlation functions under time reversal. We then show how
      these findings can be combined with a previously identified symmetry to
      determine, for example, null components of the correlation functions of
      velocities and currents and of the associated transport coefficients. These
      theoretical predictions are illustrated by molecular dynamics simulations of
      superionic AgI.

PMID- 29347192
TI  - Endoreversible quantum heat engines in the linear response regime.
AB  - We analyze general models of quantum heat engines operating a cycle of two
      adiabatic and two isothermal processes. We use the quantum master equation for a
      system to describe heat transfer current during a thermodynamic process in
      contact with a heat reservoir, with no use of phenomenological thermal
      conduction. We apply the endoreversibility description to such engine models
      working in the linear response regime and derive expressions of the efficiency
      and the power. By analyzing the entropy production rate along a single cycle, we
      identify the thermodynamic flux and force that a linear relation connects. From
      maximizing the power output, we find that such heat engines satisfy the tight
      coupling condition and the efficiency at maximum power agrees with the Curzon
      Ahlborn efficiency known as the upper bound in the linear response regime.

PMID- 29347193
TI  - Pseudo-Hermitian anti-Hermitian ensemble of Gaussian matrices.
AB  - It is shown that the ensemble of pseudo-Hermitian Gaussian matrices recently
      introduced gives rise in a certain limit to an ensemble of anti-Hermitian
      matrices whose eigenvalues have properties directly related to those of the
      chiral ensemble of random matrices.

PMID- 29347194
TI  - Comment on "Flow of wet granular materials: A numerical study".
AB  - The effective stress model of Khamseh et al., Phys. Rev. E 92, 022201
      (2015)PLEEE81539-375510.1103/PhysRevE.92.022201 is in semiquantitative agreement
      with the shear stress in simulated steady state flow of a wet granular material.
      Nonetheless, the predictions are increasingly biased at low normal pressure. The
      approximation of the capillary stress by a spherical tensor in this model is a
      sufficient cause of the prediction errors, as shown in this Comment. The re
      examination reveals an excellent agreement between the data and the effective
      stress expression formerly introduced for similar systems, further validating a
      yet unexplained empirical result.

PMID- 29347195
TI  - Floquet analysis of Kuznetsov-Ma breathers: A path towards spectral stability of
      rogue waves.
AB  - In the present work, we aim at taking a step towards the spectral stability
      analysis of Peregrine solitons, i.e., wave structures that are used to emulate
      extreme wave events. Given the space-time localized nature of Peregrine solitons,
      this is a priori a nontrivial task. Our main tool in this effort will be the
      study of the spectral stability of the periodic generalization of the Peregrine
      soliton in the evolution variable, namely the Kuznetsov-Ma breather. Given the
      periodic structure of the latter, we compute the corresponding Floquet
      multipliers, and examine them in the limit where the period of the orbit tends to
      infinity. This way, we extrapolate towards the stability of the limiting
      structure, namely the Peregrine soliton. We find that multiple unstable modes of
      the background are enhanced, yet no additional unstable eigenmodes arise as the
      Peregrine limit is approached. We explore the instability evolution also in
      direct numerical simulations.

PMID- 29347196
TI  - Iterative control strategies for nonlinear systems.
AB  - In this paper, we focus on the control of the mean-field equilibrium of nonlinear
      networks of the Langevin type in the limit of small noise. Using iterative linear
      approximations, we derive a formula that prescribes a control strategy in order
      to displace the equilibrium state of a given system and remarkably find that the
      control function has a "universal" form under certain physical conditions. This
      result can be employed to define universal protocols useful, for example, in the
      optimal work extraction from a given reservoir. Generalizations and limits of
      application of the method are discussed.

PMID- 29347197
TI  - Dynamical crossover in a stochastic model of cell fate decision.
AB  - We study the asymptotic behaviors of stochastic cell fate decision between
      proliferation and differentiation. We propose a model of a self-replicating
      Langevin system, where cells choose their fate (i.e., proliferation or
      differentiation) depending on local cell density. Based on this model, we propose
      a scenario for multicellular organisms to maintain the density of cells (i.e.,
      homeostasis) through finite-ranged cell-cell interactions. Furthermore, we
      numerically show that the distribution of the number of descendant cells changes
      over time, thus unifying the previously proposed two models regarding
      homeostasis: the critical birth death process and the voter model. Our results
      provide a general platform for the study of stochastic cell fate decision in
      terms of nonequilibrium statistical mechanics.

PMID- 29347198
TI  - Supercritical Gruneisen parameter and its universality at the Frenkel line.
AB  - We study the thermomechanical properties of matter under extreme conditions deep
      in the supercritical state, at temperatures exceeding the critical one by up to
      four orders of magnitude. We calculate the Gruneisen parameter gamma and find
      that on isochores it decreases with temperature from 3 to 1, depending on the
      density. Our results indicate that from the perspective of thermomechanical
      properties, the supercritical state is characterized by a wide range of gamma's
      which includes solidlike values-an interesting finding in view of the common
      perception of the supercritical state as being an intermediate state between
      gases and liquids. We rationalize this result by considering the relative weights
      of oscillatory and diffusive components of the supercritical system below the
      Frenkel line. We also find that gamma is nearly constant at the Frenkel line
      above the critical point and explain this universality in terms of the pressure
      and temperature scaling of system properties along the lines where particle
      dynamics changes qualitatively.

PMID- 29347199
TI  - Single and double linear and nonlinear flatband chains: Spectra and modes.
AB  - We report results of systematic analysis of various modes in the flatband
      lattice, based on the diamond-chain model with the on-site cubic nonlinearity,
      and its double version with the linear on-site mixing between the two lattice
      fields. In the single-chain system, a full analysis is presented, first, for the
      single nonlinear cell, making it possible to find all stationary states, viz.,
      antisymmetric, symmetric, and asymmetric ones, including an exactly investigated
      symmetry-breaking bifurcation of the subcritical type. In the nonlinear infinite
      single-component chain, compact localized states (CLSs) are found in an exact
      form too, as an extension of known compact eigenstates of the linear diamond
      chain. Their stability is studied by means of analytical and numerical methods,
      revealing a nontrivial stability boundary. In addition to the CLSs, various
      species of extended states and exponentially localized lattice solitons of
      symmetric and asymmetric types are also studied, by means of numerical
      calculations and variational approximation. As a result, existence and stability
      areas are identified for these modes. Finally, the linear version of the double
      diamond chain is solved in an exact form, producing two split flatbands in the
      system's spectrum.

PMID- 29347200
TI  - Apparent slip of shear thinning fluid in a microchannel with a superhydrophobic
      wall.
AB  - The peculiarities of simple shear flow of shear thinning fluids over a
      superhydrophobic wall consisting of a set of parallel gas-filled grooves and
      solid stripes (domains with slip and stick boundary conditions) are studied
      numerically. The Carreau-Yasuda model is used to provide further insight into the
      problem of the slip behavior of non-Newtonian fluids having a decreasing
      viscosity with a shear rate increase. This feature is demonstrated to cause a
      nonlinear velocity profile leading to the apparent slip. The corresponding
      transverse and longitudinal apparent slip lengths of a striped texture are found
      to be noticeably larger than the respective effective slip lengths of Newtonian
      liquids in microchannels of various thicknesses and surface fractions of the slip
      domains. The viscosity distribution of the shear thinning fluid over the
      superhydrophobic wall is carefully investigated to describe the mechanism of the
      apparent slip. Nonmonotonic behavior of the apparent slip length as a function of
      the applied shear rate is revealed. This important property of shear thinning
      fluids is considered to be sensitive to the steepness of the viscosity flow
      curve, thus providing a way to decrease considerably the flow resistance in
      microchannels.

PMID- 29347201
TI  - Stiffening thermal membranes by cutting.
AB  - Two-dimensional crystalline membranes have recently been realized experimentally
      in systems such as graphene and molybdenum disulfide, sparking a resurgence in
      interest in their statistical properties. Thermal fluctuations can significantly
      affect the effective mechanical properties of properly thermalized membranes,
      renormalizing both bending rigidity and elastic moduli so that in particular they
      become stiffer to bending than their bare bending rigidity would suggest. We use
      molecular dynamics simulations to examine how the mechanical behavior of
      thermalized two-dimensional clamped ribbons (cantilevers) depends on their
      precise topology and geometry. We find that a simple slit smooths roughness as
      measured by the variance of height fluctuations. This counterintuitive effect may
      be due to the counterposed coupling of the lips of the slit to twist in the
      intact regions of the ribbon.

PMID- 29347202
TI  - Graphene as transmissive electrodes and aligning layers for liquid-crystal-based
      electro-optic devices.
AB  - In a conventional liquid crystal (LC) cell, polyimide layers are used to align
      the LC homogeneously in the cell, and transmissive indium tin oxide (ITO)
      electrodes are used to apply the electric field to reorient the LC along the
      field. It is experimentally presented here that monolayer graphene films on the
      two glass substrates can function concurrently as the LC aligning layers and the
      transparent electrodes to fabricate an LC cell, without using the conventional
      polyimide and ITO substrates. This replacement can effectively decrease the
      thickness of all the alignment layers and electrodes from about 100 nm to less
      than 1 nm. The interaction between LC and graphene through pi-pi electron
      stacking imposes a planar alignment on the LC in the graphene-based cell-which is
      verified using a crossed polarized microscope. The graphene-based LC cell
      exhibits an excellent nematic director reorientation process from planar to
      homeotropic configuration through the application of an electric field-which is
      probed by dielectric and electro-optic measurements. Finally, it is shown that
      the electro-optic switching is significantly faster in the graphene-based LC cell
      than in a conventional ITO-polyimide LC cell.

PMID- 29347203
TI  - Dynamical properties of the herding voter model with and without noise.
AB  - Collective leadership and herding may arise in standard models of opinion
      dynamics as an interplay of a strong separation of time scales within the
      population and its hierarchical organization. Using the voter model as a simple
      opinion formation model, we show that, in the herding phase, a group of agents
      become effectively the leaders of the dynamics while the rest of the population
      follow blindly their opinion. Interestingly, in some cases such herding dynamics
      accelerates the time to consensus, which then becomes size independent or, on the
      contrary, makes the consensus nearly impossible. These behaviors have important
      consequences when an external noise is added to the system that makes consensus
      (absorbing) states to disappear. We analyze this model, which shows an
      interesting phase diagram, with a purely diffusive phase, a herding (or two
      states) phase, and mixed phases where both behaviors are possible.

PMID- 29347204
TI  - Magnetic-field-driven alteration in capillary filling dynamics in a narrow
      fluidic channel.
AB  - We investigated pressure-driven transport of an immiscible binary system,
      constituted by two electrically conducting liquids, in a narrow fluidic channel
      under the influence of an externally applied magnetic field. The surface
      wettability was taken into account in the analysis considering that the walls of
      the channel are chemically treated to obtain various predefined contact angles as
      required for the study. Alterations in the capillary filling and wetting dynamics
      in the channel stemming from a complex interplay among different forces acting
      over the interface were investigated. It was shown that an alteration in the
      strength of the magnetic field leads to an alteration in the dynamics of the
      interface, which in turn, alters the filling and wetting dynamics nontrivially
      upon interaction with the surface tension force due to the wetted walls of the
      channel. It is emphasized that a contrast in properties of constituents of the
      binary system gives rise to an alteration in the forces being applied across the
      interface, leading to an intricate control over the filling and wetting dynamics
      for a given flow configuration and an applied field strength. We believe that the
      results obtained from this analysis may aid the design of microfluidic devices
      used for multiphase transport.

PMID- 29347205
TI  - Inferring network structure from cascades.
AB  - Many physical, biological, and social phenomena can be described by cascades
      taking place on a network. Often, the activity can be empirically observed, but
      not the underlying network of interactions. In this paper we offer three
      topological methods to infer the structure of any directed network given a set of
      cascade arrival times. Our formulas hold for a very general class of models where
      the activation probability of a node is a generic function of its degree and the
      number of its active neighbors. We report high success rates for synthetic and
      real networks, for several different cascade models.

PMID- 29347206
TI  - Detection of time delays and directional interactions based on time series from
      complex dynamical systems.
AB  - Data-based and model-free accurate identification of intrinsic time delays and
      directional interactions is an extremely challenging problem in complex dynamical
      systems and their networks reconstruction. A model-free method with new scores is
      proposed to be generally capable of detecting single, multiple, and distributed
      time delays. The method is applicable not only to mutually interacting dynamical
      variables but also to self-interacting variables in a time-delayed feedback loop.
      Validation of the method is carried out using physical, biological, and
      ecological models and real data sets. Especially, applying the method to air
      pollution data and hospital admission records of cardiovascular diseases in Hong
      Kong reveals the major air pollutants as a cause of the diseases and, more
      importantly, it uncovers a hidden time delay (about 30-40 days) in the causal
      influence that previous studies failed to detect. The proposed method is expected
      to be universally applicable to ascertaining and quantifying subtle interactions
      (e.g., causation) in complex systems arising from a broad range of disciplines.

PMID- 29347207
TI  - Role of anchoring energy on the texture of cholesteric droplets: Finite-element
      simulations and experiments.
AB  - We present a numerical method to compute defect-free textures inside cholesteric
      domains of arbitrary shape. This method has two interesting properties, namely a
      robust and fast quadratic convergence to a local minimum of the Frank free
      energy, thanks to a trust region strategy. We apply this algorithm to study the
      texture of cholesteric droplets in coexistence with their isotropic liquid in two
      cases: when the anchoring is planar and when it is tilted. In the first case, we
      show how to determine the anchoring energy at the cholesteric-isotropic interface
      from a study of the optical properties of droplets of different sizes oriented
      with an electric field. This method is applied to the case of the liquid crystal
      CCN-37. In the second case, we come back to the issue of the textural transition
      as a function of the droplet radius between the double-twist droplets and the
      banded droplets, observed for instance in cyanobiphenyl liquid crystals. We show
      that, even if this transition is dominated by the saddle-splay Gauss constant
      K_{4}, as was recently recognized by Yoshioka et al. [Soft Matter 12, 2400
      (2016)1744-683X10.1039/C5SM02838H], the anchoring energy does also play an
      important role that cannot be neglected.

PMID- 29347208
TI  - Colloid-colloid hydrodynamic interaction around a bend in a quasi-one-dimensional
      channel.
AB  - We report a study of how a bend in a quasi-one-dimensional (q1D) channel
      containing a colloid suspension at equilibrium that exhibits single-file particle
      motion affects the hydrodynamic coupling between colloid particles. We observe
      both structural and dynamical responses as the bend angle becomes more acute. The
      structural response is an increasing depletion of particles in the vicinity of
      the bend and an increase in the nearest-neighbor separation in the pair
      correlation function for particles on opposite sides of the bend. The dynamical
      response monitored by the change in the self-diffusion [D_{11}(x)] and coupling
      [D_{12}(x)] terms of the pair diffusion tensor reveals that the pair separation
      dependence of D_{12} mimics that of the pair correlation function just as in a
      straight q1D channel. We show that the observed behavior is a consequence of the
      boundary conditions imposed on the q1D channel: both the single-file motion and
      the hydrodynamic flow must follow the channel around the bend.

PMID- 29347209
TI  - Takeover times for a simple model of network infection.
AB  - We study a stochastic model of infection spreading on a network. At each time
      step a node is chosen at random, along with one of its neighbors. If the node is
      infected and the neighbor is susceptible, the neighbor becomes infected. How many
      time steps T does it take to completely infect a network of N nodes, starting
      from a single infected node? An analogy to the classic "coupon collector" problem
      of probability theory reveals that the takeover time T is dominated by extremal
      behavior, either when there are only a few infected nodes near the start of the
      process or a few susceptible nodes near the end. We show that for N?1, the
      takeover time T is distributed as a Gumbel distribution for the star graph, as
      the convolution of two Gumbel distributions for a complete graph and an Erdos
      Renyi random graph, as a normal for a one-dimensional ring and a two-dimensional
      lattice, and as a family of intermediate skewed distributions for d-dimensional
      lattices with d>=3 (these distributions approach the convolution of two Gumbel
      distributions as d approaches infinity). Connections to evolutionary dynamics,
      cancer, incubation periods of infectious diseases, first-passage percolation, and
      other spreading phenomena in biology and physics are discussed.

PMID- 29347210
TI  - Eigenvector centrality for geometric and topological characterization of porous
      media.
AB  - Solving flow and transport through complex geometries such as porous media is
      computationally difficult. Such calculations usually involve the solution of a
      system of discretized differential equations, which could lead to extreme
      computational cost depending on the size of the domain and the accuracy of the
      model. Geometric simplifications like pore networks, where the pores are
      represented by nodes and the pore throats by edges connecting pores, have been
      proposed. These models, despite their ability to preserve the connectivity of the
      medium, have difficulties capturing preferential paths (high velocity) and
      stagnation zones (low velocity), as they do not consider the specific relations
      between nodes. Nonetheless, network theory approaches, where a complex network is
      a graph, can help to simplify and better understand fluid dynamics and transport
      in porous media. Here we present an alternative method to address these issues
      based on eigenvector centrality, which has been corrected to overcome the
      centralization problem and modified to introduce a bias in the centrality
      distribution along a particular direction to address the flow and transport
      anisotropy in porous media. We compare the model predictions with millifluidic
      transport experiments, which shows that, albeit simple, this technique is
      computationally efficient and has potential for predicting preferential paths and
      stagnation zones for flow and transport in porous media. We propose to use the
      eigenvector centrality probability distribution to compute the entropy as an
      indicator of the "mixing capacity" of the system.

PMID- 29347211
TI  - Dependence of the configurational entropy on amorphous structures of a hard
      sphere fluid.
AB  - The free energy of a hard-sphere fluid for which the average energy is trivial
      signifies how its entropy changes with packing. The packing eta_{f} at which the
      free energy of the crystalline state becomes lower than that of the disordered
      fluid state marks the freezing point. For packing fractions eta>eta_{f} of the
      hard-sphere fluid, we use the modified weighted density functional approximation
      to identify metastable free energy minima intermediate between uniform fluid and
      crystalline states. The distribution of the sharply localized density profiles,
      i.e., the inhomogeneous density field rho(x) characterizing the metastable state
      is primarily described by a pair function g_{s}(eta/eta_{0}). eta_{0} is a
      structural parameter such that for eta=eta_{0} the pair function is identical to
      that for the Bernal random structure. The configurational entropy S_{c} of the
      metastable hard-sphere fluid is calculated by subtracting the corresponding
      vibrational entropy from the total entropy. The extrapolated S_{c} vanishes as
      eta->eta_{K} and eta_{K} is in agreement with other works. The dependence of
      eta_{K} on the structural parameter eta_{0} is obtained.

PMID- 29347212
TI  - Theory of microphase separation in bidisperse chiral membranes.
AB  - We present a Ginzburg-Landau theory of microphase separation in a bidisperse
      chiral membrane consisting of rods of opposite handedness. This model system
      undergoes a phase transition from an equilibrium state where the two components
      are completely phase separated to a state composed of microdomains of a finite
      size comparable to the twist penetration depth. Characterizing the phenomenology
      using linear stability analysis and numerical studies, we trace the origin of the
      discontinuous change in microdomain size that occurs during this phase transition
      to a competition between the cost of creating an interface and the gain in twist
      energy for small microdomains in which the twist penetrates deep into the center
      of the domain.

PMID- 29347213
TI  - Nonlinear dispersive waves in repulsive lattices.
AB  - The propagation of nonlinear waves in a lattice of repelling particles is studied
      theoretically and experimentally. A simple experimental setup is proposed,
      consisting of an array of coupled magnetic dipoles. By driving harmonically the
      lattice at one boundary, we excite propagating waves and demonstrate different
      regimes of mode conversion into higher harmonics, strongly influenced by
      dispersion and discreteness. The phenomenon of acoustic dilatation of the chain
      is also predicted and discussed. The results are compared with the theoretical
      predictions of the alpha-Fermi-Pasta-Ulam equation, describing a chain of masses
      connected by nonlinear quadratic springs and numerical simulations. The results
      can be extrapolated to other systems described by this equation.

PMID- 29347214
TI  - Quantum Hamiltonian daemons: Unitary analogs of combustion engines.
AB  - Hamiltonian daemons have recently been defined classically as small, closed
      Hamiltonian systems which can exhibit secular energy transfer from high-frequency
      to low-frequency degrees of freedom (steady downconversion), analogous to the
      steady transfer of energy in a combustion engine from the high terahertz
      frequencies of molecular excitations to the low kilohertz frequencies of piston
      motion [L. Gilz, E. P. Thesing, and J. R. Anglin, Phys. Rev. E 94, 042127
      (2016)2470-004510.1103/PhysRevE.94.042127]. Classical daemons achieve
      downconversion within a small, closed system by exploiting nonlinear resonances;
      the adiabatic theorem permits their operation but imposes nontrivial limitations
      on their efficiency. Here we investigate a simple example of a quantum mechanical
      daemon. In the correspondence regime it obeys similar efficiency limits to its
      classical counterparts, but in the strongly quantum mechanical regime the daemon
      operates in an entirely different manner. It maintains an engine-like behavior in
      a distinctly quantum mechanical form: a weight is lifted at a steady average
      speed through a long sequence of quantum jumps in momentum, at each of which a
      quantum of fuel is consumed. The quantum daemon can cease downconversion at any
      time through nonadiabatic Landau-Zener transitions, and continuing operation of
      the quantum daemon is associated with steadily growing entanglement between fast
      and slow degrees of freedom.

PMID- 29347215
TI  - Optomechanical proposal for monitoring microtubule mechanical vibrations.
AB  - Microtubules provide the mechanical force required for chromosome separation
      during mitosis. However, little is known about the dynamic (high-frequency)
      mechanical properties of microtubules. Here, we theoretically propose to control
      the vibrations of a doubly clamped microtubule by tip electrodes and to detect
      its motion via the optomechanical coupling between the vibrational modes of the
      microtubule and an optical cavity. In the presence of a red-detuned strong pump
      laser, this coupling leads to optomechanical-induced transparency of an optical
      probe field, which can be detected with state-of-the art technology. The center
      frequency and line width of the transparency peak give the resonance frequency
      and damping rate of the microtubule, respectively, while the height of the peak
      reveals information about the microtubule-cavity field coupling. Our method opens
      the new possibilities to gain information about the physical properties of
      microtubules, which will enhance our capability to design physical cancer
      treatment protocols as alternatives to chemotherapeutic drugs.

PMID- 29347216
TI  - Ordering phenomena in a heterostructure of frustrated and unfrustrated triangular
      lattice Ising layers.
AB  - We study critical and magnetic properties of a bilayer Ising system consisting of
      two triangular planes A and B, with the antiferromagnetic (AF) coupling J_{A} and
      the ferromagnetic (FM) one J_{B} for the respective layers, which are coupled by
      the interlayer interaction J_{AB} by using Monte Carlo simulations. When J_{A}
      and J_{B} are of the same order, the unfrustrated FM plane orders first at a high
      temperature T_{c1}~J_{B}. The spontaneous FM order then exerts influence on the
      other frustrated AF plane as an effective magnetic field, which subsequently
      induces a ferrimagnetic order in this plane at low temperatures below T_{c2}.
      When short-range order is developed in the AF plane while the influence of the FM
      plane is still small, there appears a preemptive Berezinskii-Kosterlitz-Thouless
      type pseudocritical crossover regime just above the ferrimagnetic phase
      transition point, where the short-distance behavior up to a rather large length
      scale exponentially diverging in ?J_{A}/T is controlled by a line of Gaussian
      fixed points at T=0. In the crossover region, a continuous variation in the
      effective critical exponent 4/9?eta^{eff}?1/2 is observed. The phase diagram by
      changing the ratio J_{A}/J_{B} is also investigated.

PMID- 29347217
TI  - Aging in the three-dimensional random-field Ising model.
AB  - We studied the nonequilibrium aging behavior of the random-field Ising model in
      three dimensions for various values of the disorder strength. This allowed us to
      investigate how the aging behavior changes across the ferromagnetic-paramagnetic
      phase transition. We investigated a large system size of N=256^{3} spins and up
      to 10^{8} Monte Carlo sweeps. To reach these necessary long simulation times, we
      employed an implementation running on Intel Xeon Phi coprocessors, reaching
      single-spin-flip times as short as 6 ps. We measured typical correlation
      functions in space and time to extract a growing length scale and corresponding
      exponents.

PMID- 29347218
TI  - Effect of particle-size dynamics on properties of dense spongy-particle systems:
      Approach towards equilibrium.
AB  - Open-porous deformable particles, often envisaged as sponges, are ubiquitous in
      biological and industrial systems (e.g., casein micelles in dairy products and
      microgels in cosmetics). The rich behavior of these suspensions is owing to the
      elasticity of the supporting network of the particle, and the viscosity of
      permeating solvent. Therefore, the rate-dependent size change of these particles
      depends on their structure, i.e., the permeability. This work aims at
      investigating the effect of the particle-size dynamics and the underlying
      particle structure, i.e., the particle permeability, on the transient and long
      time behavior of suspensions of spongy particles in the absence of applied
      deformation, using the dynamic two-scale model developed by Hutter et al. [Farad.
      Discuss. 158, 407 (2012)1359-664010.1039/c2fd20025b]. In the high-density limit,
      the transient behavior is found to be accelerated by the particle-size dynamics,
      even at average size changes as small as 1%. The accelerated dynamics is
      evidenced by (i) the higher short-time diffusion coefficient as compared to
      elastic-particle systems and (ii) the accelerated formation of the stable fcc
      crystal structure. Furthermore, after long times, the particle-size dynamics of
      spongy particles is shown to result in lower stationary values of the energy and
      normal stresses as compared to elastic-particle systems. This dependence of the
      long-time behavior of these systems on the permeability, that essentially is a
      transport coefficient and hence must not affect the equilibrium properties,
      confirms that full equilibration has not been reached.

PMID- 29347219
TI  - Transport and diffusion properties of Brownian particles powered by a rotating
      wheel.
AB  - Diffusion and rectification of Brownian particles powered by a rotating wheel are
      numerically investigated in a two-dimensional channel. The nonequilibrium driving
      comes from the rotating wheel, which can break thermodynamical equilibrium and
      induce the directed transport in an asymmetric potential. It is found that the
      direction of the transport along the potential is determined by the asymmetry of
      the potential and the position of the wheel. The average velocity is a peaked
      function of the angular speed (or the diffusion coefficient) and the position of
      the peak shifts to large angular speed (or diffusion coefficient) when the
      diffusion coefficient (or the angular speed) increases. There exists an optimal
      angular speed (or diffusion coefficient) at which the effective diffusion
      coefficient takes its maximal value. Remarkably, the giant acceleration of
      diffusion is observed by suitably adjusting the system parameters. The parameters
      corresponding to the maximum effective diffusion coefficient are not the same as
      the parameters at which average velocity is maximum.

PMID- 29347220
TI  - Geometrical properties of rigid frictionless granular packings as a function of
      particle size and shape.
AB  - Three-dimensional discrete numerical simulation is used to investigate the
      properties of close-packed frictionless granular assemblies as a function of
      particle polydispersity and shape. Unlike some experimental results, simulations
      show that disordered packings of pinacoids (eight-face convex polyhedra) achieve
      higher solid fraction values than amorphous packings of spherical or rounded
      particles, thus fulfilling the analog of Ulam's conjecture stated by Jiao and co
      workers for random packings [Y. Jiao and S. Torquato, Phys. Rev. E 84, 041309
      (2011)PLEEE81539-375510.1103/PhysRevE.84.041309]. This seeming discrepancy
      between experimental and numerical results is believed to result from
      difficulties in overcoming inter particle friction through experimental
      densification processes. Moreover, solid fraction is shown to increase further
      with bidispersity and peak when the volume proportion of small particles reaches
      30%. Contrarily, substituting up to 50% of flat pinacoids for isometric ones
      yields solid fraction decrease, especially when flat particles are also
      elongated. Nevertheless, particle shape seems to play a minor role in packing
      solid fraction compared to polydispersity. Additional investigations focused on
      the packing microstructure confirm that pinacoid packings fulfill the isostatic
      conjecture and that they are free of order except beyond 30% to 50% of flat or
      flat-elongated polyhedra in the packing. This order increase progressively takes
      the form of a nematic phase caused by the reorientation of flat or flat-elongated
      particles to minimize the packing potential energy. Simultaneously, this
      reorientation seems to increase the solid fraction value slightly above the
      maximum achieved by monodisperse isometric pinacoids, as well as the coordination
      number. Finally, partial substitution of elongated pinacoids for isometric ones
      has limited effect on packing solid fraction or order.

PMID- 29347221
TI  - Production rate of the system-bath mutual information.
AB  - When an open system comes into contact with several thermal baths, the entropy
      produced by the irreversible processes (dS_{i}=dS-?_{alpha} dQ_{alpha}/T_{alpha})
      keeps increasing, and this entropy production rate is always non-negative.
      However, when the system comes into contact with nonthermal baths containing
      quantum coherence or squeezing, this entropy production formula does not apply.
      In this paper, we study the increasing rate of mutual information between an open
      system and its environment. In the case of canonical thermal baths, we prove that
      this mutual information production rate could return exactly to the previous
      entropy production rate. Furthermore, we study an example of a single boson mode
      that comes into contact with multiple squeezed thermal baths, where the
      conventional entropy production rate does not apply, and we find that this mutual
      information production rate remains non-negative, which indicates a monotonic
      increase in the correlation between the system and its environment.

PMID- 29347222
TI  - Extremal-point density of scaling processes: From fractional Brownian motion to
      turbulence in one dimension.
AB  - In recent years several local extrema-based methodologies have been proposed to
      investigate either the nonlinear or the nonstationary time series for scaling
      analysis. In the present work, we study systematically the distribution of the
      local extrema for both synthesized scaling processes and turbulent velocity data
      from experiments. The results show that for the fractional Brownian motion (fBm)
      without intermittency correction the measured extremal-point-density (EPD) agrees
      well with a theoretical prediction. For a multifractal random walk (MRW) with the
      lognormal statistics, the measured EPD is independent of the intermittency
      parameter MU, suggesting that the intermittency correction does not change the
      distribution of extremal points but changes the amplitude. By introducing a
      coarse-grained operator, the power-law behavior of these scaling processes is
      then revealed via the measured EPD for different scales. For fBm the scaling
      exponent xi(H) is found to be xi(H)=H, where H is Hurst number, while for MRW
      xi(MU) shows a linear relation with the intermittency parameter MU. Such EPD
      approach is further applied to the turbulent velocity data obtained from a wind
      tunnel flow experiment with the Taylor scale lambda-based Reynolds number
      Re_{lambda}=720, and a turbulent boundary layer with the momentum thickness theta
      based Reynolds number Re_{theta}=810. A scaling exponent xi?0.37 is retrieved for
      the former case. For the latter one, the measured EPD shows clearly four regimes,
      which agrees well with the corresponding sublayer structures inside the turbulent
      boundary layer.

PMID- 29347223
TI  - Metal nanospheres under intense continuous-wave illumination: A unique case of
      nonperturbative nonlinear nanophotonics.
AB  - We show that the standard perturbative (i.e., cubic) description of the thermal
      nonlinear response of a single metal nanosphere to intense continuous-wave (CW)
      illumination is sufficient only for a temperature rise of up to 100 degrees above
      room temperature. Beyond this regime, the slowing down of the temperature rise
      requires a nonperturbative description of the nonlinear response, even though the
      permittivity is linearly dependent on the temperature and despite the deep
      subwavelength effective propagation distances involved. Using experimental data,
      we show that, generically, the increase of the imaginary part of the metal
      permittivity dominates the increase of the host permittivity as well as the
      resonance shift due to the joint changes to the real parts of the metal and host.
      Thus, the main nonlinear effect is a decrease of the quality factor of the
      resonance. We further analyze the relative importance of the various
      contributions to the temperature rise and thermal nonlinearity, compare the
      nonlinearity of Au and Ag, demonstrate the potential effect of the nanoparticle
      morphology, and show that although the thermo-optical nonlinearity of the host
      typically plays a minor role, its thermal conductivity and its temperature
      dependence is important. Finally, we discuss the differences between CW and
      ultrafast thermal nonlinearities.

PMID- 29347224
TI  - Spreading law of non-Newtonian power-law liquids on a spherical substrate by an
      energy-balance approach.
AB  - The spreading of a cap-shaped spherical droplet of non-Newtonian power-law
      liquids, both shear-thickening and shear-thinning liquids, that completely wet a
      spherical substrate is theoretically investigated in the capillary-controlled
      spreading regime. The crater-shaped droplet model with the wedge-shaped meniscus
      near the three-phase contact line is used to calculate the viscous dissipation
      near the contact line. Then the energy balance approach is adopted to derive the
      equation that governs the evolution of the contact line. The time evolution of
      the dynamic contact angle theta of a droplet obeys a power law theta~t^{-alpha}
      with the spreading exponent alpha, which is different from Tanner's law for
      Newtonian liquids and those for non-Newtonian liquids on a flat substrate.
      Furthermore, the line-tension dominated spreading, which could be realized on a
      spherical substrate for late-stage of spreading when the contact angle becomes
      low and the curvature of the contact line becomes large, is also investigated.

PMID- 29347225
TI  - First-principles equation of state and shock compression predictions of warm
      dense hydrocarbons.
AB  - We use path integral Monte Carlo and density functional molecular dynamics to
      construct a coherent set of equations of state (EOS) for a series of hydrocarbon
      materials with various C:H ratios (2:1, 1:1, 2:3, 1:2, and 1:4) over the range of
      0.07-22.4gcm^{-3} and 6.7*10^{3}-1.29*10^{8}K. The shock Hugoniot curve derived
      for each material displays a single compression maximum corresponding to K-shell
      ionization. For C:H = 1:1, the compression maximum occurs at 4.7-fold of the
      initial density and we show radiation effects significantly increase the shock
      compression ratio above 2 Gbar, surpassing relativistic effects. The single
      peaked structure of the Hugoniot curves contrasts with previous work on higher-Z
      plasmas, which exhibit a two-peak structure corresponding to both K- and L-shell
      ionization. Analysis of the electronic density of states reveals that the change
      in Hugoniot structure is due to merging of the L-shell eigenstates in carbon,
      while they remain distinct for higher-Z elements. Finally, we show that the
      isobaric-isothermal linear mixing rule for carbon and hydrogen EOS is a
      reasonable approximation with errors better than 1% for stellar-core conditions.

PMID- 29347226
TI  - Diffusion in time-dependent random media and the Kardar-Parisi-Zhang equation.
AB  - Although time-dependent random media with short-range correlations lead to
      (possibly biased) normal tracer diffusion, anomalous fluctuations occur away from
      the most probable direction. This was pointed out recently in one-dimensional
      (1D) lattice random walks, where statistics related to the 1D Kardar-Parisi-Zhang
      (KPZ) universality class, i.e., the Gaussian unitary ensemble Tracy-Widom
      distribution, were shown to arise. Here, we provide a simple picture for this
      correspondence, directly in the continuum, which allows one to study arbitrary
      space dimensions and to predict a variety of universal distributions. In d=1, we
      predict and verify numerically the emergence of the Gaussian orthogonal ensemble
      Tracy-Widom distribution for fluctuations of the transition probability. In d=3,
      we predict a phase transition from Gaussian fluctuations to three-dimensional KPZ
      type fluctuations as the bias is increased. We predict KPZ universal
      distributions for the arrival time of a first particle from a cloud diffusing in
      such media.

PMID- 29347227
TI  - Thomas-Fermi simulations of dense plasmas without pseudopotentials.
AB  - The Thomas-Fermi model for warm and hot dense matter is widely used to predict
      material properties such as the equation of state. However, for practical reasons
      current implementations use pseudopotentials for the electron-nucleus interaction
      instead of the bare Coulomb potential. This complicates the calculation and
      quantities such as free energy cannot be converged with respect to the
      pseudopotential parameters. We present a method that retains the bare Coulomb
      potential for the electron-nucleus interaction and does not use pseudopotentials.
      We demonstrate that accurate free energies are obtained by checking variational
      consistency. Examples for aluminum and iron plasmas are presented.

PMID- 29347228
TI  - Dynamics of spinning particle pairs in a single-layer complex plasma crystal.
AB  - Spontaneous formation of spinning pairs of particles, or torsions, is studied in
      a single-layer complex plasma crystal by reducing the discharge power at constant
      neutral gas pressure. At higher gas pressures, torsions spontaneously form below
      a certain power threshold. Further reduction of the discharge power leads to the
      formation of multiple torsions. However, at lower gas pressures the torsion
      formation is preceded by mode-coupling instability (MCI). The crystal dynamics
      are studied with the help of the fluctuation spectra of crystal particles' in
      plane velocities. Surprisingly, the spectra of the crystal with torsions and MCI
      are rather similar and contain hot spots at similar locations on the (k,omega)
      plane, despite very different appearances of the respective particle
      trajectories. The torsion rotation speed is close (slightly below) to the maximum
      frequency of the in-plane compressional mode. When multiple torsions form, their
      rotation speeds are distributed in a narrow range slightly below the maximum
      frequency.

PMID- 29347229
TI  - Phase diagram and criticality of the two-dimensional prisoner's dilemma model.
AB  - The stationary states of the prisoner's dilemma model are studied on a square
      lattice taking into account the role of a noise parameter in the decision-making
      process. Only first neighboring players-defectors and cooperators-are considered
      in each step of the game. Through Monte Carlo simulations we determined the phase
      diagrams of the model in the plane noise versus the temptation to defect for a
      large range of values of the noise parameter. We observed three phases:
      cooperators and defectors absorbing phases, and a coexistence phase between them.
      The phase transitions as well as the critical exponents associated with them were
      determined using both static and dynamical scaling laws.

PMID- 29347230
TI  - Detecting unstable periodic orbits in chaotic time series using synchronization.
AB  - An alternative approach of detecting unstable periodic orbits in chaotic time
      series is proposed using synchronization techniques. A master-slave
      synchronization scheme is developed, in which the chaotic system drives a system
      of harmonic oscillators through a proper coupling condition. The proposed scheme
      is designed so that the power of the coupling signal exhibits notches that drop
      to zero once the system approaches an unstable orbit yielding an explicit
      indication of the presence of a periodic motion. The results shows that the
      proposed approach is particularly suitable in practical situations, where the
      time series is short and noisy, or it is obtained from high-dimensional chaotic
      systems.

PMID- 29347231
TI  - Reconstructing networks of pulse-coupled oscillators from spike trains.
AB  - We present an approach for reconstructing networks of pulse-coupled neuronlike
      oscillators from passive observation of pulse trains of all nodes. It is assumed
      that units are described by their phase response curves and that their phases are
      instantaneously reset by incoming pulses. Using an iterative procedure, we
      recover the properties of all nodes, namely their phase response curves and
      natural frequencies, as well as strengths of all directed connections.

PMID- 29347232
TI  - Continuous-time random walk under time-dependent resetting.
AB  - Continuous-time random walks of a particle that is randomly reset to an initial
      position are considered. The distribution of the waiting time between the reset
      events is represented as a sum of an arbitrary number of exponentials. The
      governing equation of this stochastic process is established. The mean first
      passage time to a particular position is calculated. It is shown that anomalous
      subdiffusion has a significant impact on the shape of the stationary state.

PMID- 29347233
TI  - Dynamics and energy spectra of aperiodic discrete-time quantum walks.
AB  - We investigate the role of different aperiodic sequences in the dynamics of
      single quantum particles in discrete space and time. For this we consider three
      aperiodic sequences, namely, the Fibonacci, Thue-Morse, and Rudin-Shapiro
      sequences, as examples of tilings the diffraction spectra of which have pure
      point, singular continuous, and absolutely continuous support, respectively. Our
      interest is to understand how the order, intrinsically introduced by the
      deterministic rule used to generate the aperiodic sequences, is reflected in the
      dynamical properties of the quantum system. For this system we consider a single
      particle undergoing a discrete-time quantum walk (DTQW), where the aperiodic
      sequences are used to distribute the coin operations at different lattice
      positions (inhomogeneous DTQW) or by applying the same coin operation at all
      lattice sites at a given time but choosing different coin operation at each time
      step according to the chosen aperiodic sequence (time dependent DTQW). We study
      the energy spectra and the spreading of an initially localized wave packet for
      different cases, finding that in the case of Fibonacci and Thue-Morse tilings the
      system is superdiffusive, whereas in the Rudin-Shapiro case it is strongly
      subdiffusive. Trying to understand this behavior in terms of the energy spectra,
      we look at the survival amplitude as a function of time. By means of the echo we
      present strong evidence that, although the three orderings are very different as
      evidenced by their diffraction spectra, the energy spectra are all singular
      continuous except for the inhomogeneous DTQW with the Rudin-Shapiro sequence
      where it is discrete. This is in agreement with the observed strong localization
      both in real space and in the Hilbert space. Our paper is particularly
      interesting because quantum walks can be engineered in laboratories by means of
      ultracold gases or in optical waveguides, and therefore would be a perfect
      playground to study singular continuous energy spectra in a completely controlled
      quantum setup.

PMID- 29347234
TI  - Pace and patterns of magnetic swimmers in a billiard pool.
AB  - We experimentally investigate magnetic surface swimmers on water. These objects
      self-assemble from ferromagnetic microparticles and a nonmagnetic disk. They are
      floating on the liquid surface due to interface tension and move under the
      influence of a harmonically oscillating homogeneous magnetic field oriented
      vertically, which is distinguished by its amplitude and frequency. The speed of
      the surface swimmers strongly depends on these parameters. The functional
      dependencies between speed and amplitude and between speed and frequency are
      investigated by independently varying both control parameters. In the first case,
      the data obtained are in good agreement with the predicted scaling while there
      are some deviations in the latter case. Moreover, due to the interplay between
      the surface bound swimmers and the ascending liquid meniscus at the edge of the
      experimental vessel, different dynamics can be realized. We observe periodic and
      quasiperiodic trajectories in a circular vessel and aperiodic trajectories in a
      vessel shaped like a Bunimovich stadium.

PMID- 29347235
TI  - Ballistic aggregation in systems of inelastic particles: Cluster growth,
      structure, and aging.
AB  - We study far-from-equilibrium dynamics in models of freely cooling granular gas
      and ballistically aggregating compact clusters. For both the cases, from event
      driven molecular dynamics simulations, we have presented detailed results on
      structure and dynamics in space dimensions d=1 and 2. Via appropriate analyses it
      has been confirmed that the ballistic aggregation mechanism applies in d=1
      granular gases as well. Aging phenomena for this mechanism, in both the
      dimensions, have been studied via the two-time density autocorrelation function.
      This quantity is demonstrated to exhibit scaling property similar to that in the
      standard phase transition kinetics. The corresponding functional forms have been
      quantified and the outcomes have been discussed in connection with the structural
      properties. Our results on aging establish a more complete equivalence between
      the granular gas and the ballistic aggregation models in d=1.

PMID- 29347236
TI  - Importance-sampling computation of statistical properties of coupled oscillators.
AB  - We introduce and implement an importance-sampling Monte Carlo algorithm to study
      systems of globally coupled oscillators. Our computational method efficiently
      obtains estimates of the tails of the distribution of various measures of
      dynamical trajectories corresponding to states occurring with (exponentially)
      small probabilities. We demonstrate the general validity of our results by
      applying the method to two contrasting cases: the driven-dissipative Kuramoto
      model, a paradigm in the study of spontaneous synchronization; and the
      conservative Hamiltonian mean-field model, a prototypical system of long-range
      interactions. We present results for the distribution of the finite-time Lyapunov
      exponent and a time-averaged order parameter. Among other features, our results
      show most notably that the distributions exhibit a vanishing standard deviation
      but a skewness that is increasing in magnitude with the number of oscillators,
      implying that nontrivial asymmetries and states yielding rare or atypical values
      of the observables persist even for a large number of oscillators.

PMID- 29347237
TI  - Linear and nonlinear response of the Vlasov system with nonintegrable
      Hamiltonian.
AB  - Linear and nonlinear response formulas taking into account all Casimir invariants
      are derived without use of angle-action variables of a single-particle (mean
      field) Hamiltonian. This article deals mainly with the Vlasov system in a
      spatially inhomogeneous quasistationary state whose associating single-particle
      Hamiltonian is not integrable and has only one integral of the motion, the
      Hamiltonian itself. The basic strategy is to restrict the form of perturbation so
      that it keeps Casimir invariants within a linear order, and the single particle's
      probabilistic density function is smooth with respect to the single particle's
      Hamiltonian. The theory is applied for a spatially two-dimensional system and is
      confirmed by numerical simulations. A nonlinear response formula is also derived
      in a similar manner.

PMID- 29347238
TI  - Cascade replication of dissipative solitons.
AB  - We report a new effect of a cascade replication of dissipative solitons from a
      single one. It is discussed in the framework of a common model based on the one
      dimensional cubic-quintic complex Ginzburg-Landau equation in which an additional
      linear term is introduced to account the perturbation from a particular potential
      of externally applied force. The effect is demonstrated on the light beams
      propagating through a planar waveguide. The waveguide consists of a nonlinear
      layer able to guide dissipative solitons and a magneto-optic substrate. In the
      waveguide an externally applied force is considered to be an inhomogeneous
      magnetic field which is induced by modulated electric currents flowing along a
      set of conducting wires adjusted on the top of the waveguide.

PMID- 29347239
TI  - Stochastic and information-thermodynamic structures of population dynamics in a
      fluctuating environment.
AB  - Adaptation in a fluctuating environment is a process of fueling environmental
      information to gain fitness. Living systems have gradually developed strategies
      for adaptation from random and passive diversification of the phenotype to more
      proactive decision making, in which environmental information is sensed and
      exploited more actively and effectively. Understanding the fundamental relation
      between fitness and information is therefore crucial to clarify the limits and
      universal properties of adaptation. In this work, we elucidate the underlying
      stochastic and information-thermodynamic structure in this process, by deriving
      causal fluctuation relations (FRs) of fitness and information. Combined with a
      duality between phenotypic and environmental dynamics, the FRs reveal the limit
      of fitness gain, the relation of time reversibility with the achievability of the
      limit, and the possibility and condition for gaining excess fitness due to
      environmental fluctuation. The loss of fitness due to causal constraints and the
      limited capacity of real organisms is shown to be the difference between time
      forward and time-backward path probabilities of phenotypic and environmental
      dynamics. Furthermore, the FRs generalize the concept of the evolutionary stable
      state (ESS) for fluctuating environment by giving the probability that the
      optimal strategy on average can be invaded by a suboptimal one owing to rare
      environmental fluctuation. These results clarify the information-thermodynamic
      structures in adaptation and evolution.

PMID- 29347240
TI  - Social contagions on weighted networks.
AB  - We investigate critical behaviors of a social contagion model on weighted
      networks. An edge-weight compartmental approach is applied to analyze the
      weighted social contagion on strongly heterogenous networks with skewed degree
      and weight distributions. We find that degree heterogeneity cannot only alter the
      nature of contagion transition from discontinuous to continuous but also can
      enhance or hamper the size of adoption, depending on the unit transmission
      probability. We also show that the heterogeneity of weight distribution always
      hinders social contagions, and does not alter the transition type.

PMID- 29347241
TI  - Viscoinertial regime of immersed granular flows.
AB  - By means of extensive coupled molecular dynamics-lattice Boltzmann simulations,
      accounting for grain dynamics and subparticle resolution of the fluid phase, we
      analyze steady inertial granular flows sheared by a viscous fluid. We show that,
      for a broad range of system parameters (shear rate, confining stress, fluid
      viscosity, and relative fluid-grain density), the frictional strength and packing
      fraction can be described by a modified inertial number incorporating the fluid
      effect. In a dual viscous description, the effective viscosity diverges as the
      inverse square of the difference between the packing fraction and its jamming
      value, as observed in experiments. We also find that the fabric and force
      anisotropies extracted from the contact network are well described by the
      modified inertial number, thus providing clear evidence for the role of these key
      structural parameters in dense suspensions.

PMID- 29347242
TI  - Multi-phase-field model for surface and phase-boundary diffusion.
AB  - The multi-phase-field approach is generalized to treat capillarity-driven
      diffusion parallel to the surfaces and phase boundaries, i.e., the boundaries
      between a condensed phase and its vapor and the boundaries between two or
      multiple condensed phases. The effect of capillarity is modeled via curvature
      dependence of the chemical potential whose gradient gives rise to diffusion. The
      model is used to study thermal grooving on the surface of a polycrystalline body.
      Decaying oscillations of the surface profile during thermal grooving, postulated
      by Hillert long ago but reported only in few studies so far, are observed and
      discussed. Furthermore, annealing of multi-nanoclusters on a deformable free
      surface is investigated using the proposed model. Results of these simulations
      suggest that the characteristic craterlike structure with an elevated perimeter,
      observed in recent experiments, is a transient nonequilibrium state during the
      annealing process.

PMID- 29347243
TI  - Analytical scalings of the linear Richtmyer-Meshkov instability when a
      rarefaction is reflected.
AB  - The Richtmyer-Meshkov instability for the case of a reflected rarefaction is
      studied in detail following the growth of the contact surface in the linear
      regime and providing explicit analytical expressions for the asymptotic
      velocities in different physical limits. This work is a continuation of the
      similar problem when a shock is reflected [Phys. Rev. E 93, 053111 (2016)1539
      375510.1103/PhysRevE.93.053111]. Explicit analytical expressions for the
      asymptotic normal velocity of the rippled surface (deltav_{i}^{infinity}) are
      shown. The known analytical solution of the perturbations growing inside the
      rarefaction fan is coupled to the pressure perturbations between the transmitted
      shock front and the rarefaction trailing edge. The surface ripple growth
      (psi_{i}) is followed from t=0+ up to the asymptotic stage inside the linear
      regime. As in the shock reflected case, an asymptotic behavior of the form
      psi_{i}(t)?psi_{infinity}+deltav_{i}^{infinity}t is observed, where
      psi_{infinity} is an asymptotic ordinate to the origin. Approximate expressions
      for the asymptotic velocities are given for arbitrary values of the shock Mach
      number. The asymptotic velocity field is calculated at both sides of the contact
      surface. The kinetic energy content of the velocity field is explicitly
      calculated. It is seen that a significant part of the motion occurs inside a
      fluid layer very near the material surface in good qualitative agreement with
      recent simulations. The important physical limits of weak and strong shocks and
      high and low preshock density ratio are also discussed and exact Taylor
      expansions are given. The results of the linear theory are compared to
      simulations and experimental work [R. L. Holmes et al., J. Fluid Mech. 389, 55
      (1999)JFLSA70022-112010.1017/S0022112099004838; C. Mariani et al., Phys. Rev.
      Lett. 100, 254503 (2008)PRLTAO0031-900710.1103/PhysRevLett.100.254503]. The
      theoretical predictions of deltav_{i}^{infinity} and psi_{infinity} show good
      agreement with the experimental and numerical reported values.

PMID- 29347244
TI  - Marginally compact fractal trees with semiflexibility.
AB  - We study marginally compact macromolecular trees that are created by means of two
      different fractal generators. In doing so, we assume Gaussian statistics for the
      vectors connecting nodes of the trees. Moreover, we introduce bond-bond
      correlations that make the trees locally semiflexible. The symmetry of the
      structures allows an iterative construction of full sets of eigenmodes
      (notwithstanding the additional interactions that are present due to
      semiflexibility constraints), enabling us to get physical insights about the
      trees' behavior and to consider larger structures. Due to the local stiffness,
      the self-contact density gets drastically reduced.

PMID- 29347245
TI  - Kinetic Ising models with various single-spin-flip dynamics on quenched and
      annealed random regular graphs.
AB  - We investigate a kinetic Ising model with several single-spin-flip dynamics
      (including Metropolis and heat bath) on quenched and annealed random regular
      graphs. As expected, on the quenched structures all proposed algorithms reproduce
      the same results since the conditions for the detailed balance and the Boltzmann
      distribution in an equilibrium are satisfied. However, on the annealed graphs the
      situation is far less clear-the network annealing disturbs the equilibrium moving
      the system away from it. Consequently, distinct dynamics lead to different steady
      states. We show that some algorithms are more resistant to the annealed disorder,
      which causes only small quantitative changes in the model behavior. On the other
      hand, there are dynamics for which the influence of annealing on the system is
      significant, and qualitative changes arise like switching the type of phase
      transition from a continuous to a discontinuous one. We try to identify features
      of the proposed dynamics which are responsible for the above phenomenon.

PMID- 29347246
TI  - Social contagion with degree-dependent thresholds.
AB  - We investigate opinion spreading by a threshold model in a situation in which the
      influence of people is heterogeneously distributed. We assume that there is a
      coupling between the influence of an individual (measured by the out-degree) and
      the threshold for accepting a new opinion or habit. We find that if the coupling
      is strongly positive, the final state of the system will be a mix of different
      opinions. Otherwise, it will converge to a consensus state. This phenomenon
      cannot simply be explained as a phase transition, but it is a combined effect of
      mechanisms and their relative dominance in different regions of parameter space.

PMID- 29347247
TI  - Multivalent ligand-receptor-mediated interaction of small filled vesicles with a
      cellular membrane.
AB  - The ligand-receptor-mediated contacts of small sub-100-nm-sized lipid vesicles
      (or nanoparticles) with the cellular membrane are of interest in the contexts of
      cell-to-cell communication, endocytosis of membrane-coated virions, and drug
      (RNA) delivery. In all these cases, the interior of vesicles is filled by
      biologically relevant content. Despite the diversity of such systems, the
      corresponding ligand-receptor interaction possesses universal features. One of
      them is that the vesicle-membrane contacts can be accompanied by the
      redistribution of ligands and receptors between the contact and contact-free
      regions. In particular, the concentrations of ligands and receptors may become
      appreciably higher in the contact regions and their composition may there be
      different compared to that in the suspended state in the solution. A statistical
      model presented herein describes the corresponding distribution of various
      ligands and receptors and allows one to calculate the related change of the free
      energy with variation of the vesicle-engulfment extent. The results obtained are
      used to clarify the necessary conditions for the vesicle-assisted pathway of drug
      delivery.

PMID- 29347248
TI  - Transition probability generating function of a transitionless quantum parametric
      oscillator.
AB  - The transitionless tracking (TT) algorithm enables the exact tracking of quantum
      adiabatic dynamics in an arbitrary short time by adding a counterdiabatic
      Hamiltonian to the original adiabatic Hamiltonian. By applying Husimi's method
      originally developed for a quantum parametric oscillator (QPO) to the
      transitionless QPO achieved using the TT algorithm, we obtain the transition
      probability generating function with a time-dependent parameter constituted with
      solutions of the corresponding classical parametric oscillator (CPO). By
      obtaining the explicit solutions of this CPO using the phase-amplitude method, we
      find that the time-dependent parameter can be reduced to the frequency ratio
      between the Hamiltonians without and with the counterdiabatic Hamiltonian, from
      which we can easily characterize the result achieved by the TT algorithm. We
      illustrate our theory by showing the trajectories of the CPO on the classical
      phase space, which elucidate the effect of the counterdiabatic Hamiltonian of the
      QPO.

PMID- 29347249
TI  - Calculating how long it takes for a diffusion process to effectively reach steady
      state without computing the transient solution.
AB  - Mathematically, it takes an infinite amount of time for the transient solution of
      a diffusion equation to transition from initial to steady state. Calculating a
      finite transition time, defined as the time required for the transient solution
      to transition to within a small prescribed tolerance of the steady-state
      solution, is much more useful in practice. In this paper, we study estimates of
      finite transition times that avoid explicit calculation of the transient solution
      by using the property that the transition to steady state defines a cumulative
      distribution function when time is treated as a random variable. In total, three
      approaches are studied: (i) mean action time, (ii) mean plus one standard
      deviation of action time, and (iii) an approach we derive by approximating the
      large time asymptotic behavior of the cumulative distribution function. Our
      approach leads to a simple formula for calculating the finite transition time
      that depends on the prescribed tolerance delta and the (k-1)th and kth moments
      (k>=1) of the distribution. Results comparing exact and approximate finite
      transition times lead to two key findings. First, although the first two
      approaches are useful at characterizing the time scale of the transition, they do
      not provide accurate estimates for diffusion processes. Second, the new approach
      allows one to calculate finite transition times accurate to effectively any
      number of significant digits using only the moments with the accuracy increasing
      as the index k is increased.

PMID- 29347250
TI  - Nonlinear continuous-wave optical propagation in nematic liquid crystals:
      Interplay between reorientational and thermal effects.
AB  - We investigate nonlinear optical propagation of continuous-wave (CW) beams in
      bulk nematic liquid crystals. We thoroughly analyze the competing roles of
      reorientational and thermal nonlinearity with reference to self
      focusing/defocusing and, eventually, the formation of nonlinear diffraction-free
      wavepackets, the so-called spatial optical solitons. To this extent we refer to
      dye-doped nematic liquid crystals in planar cells excited by a single CW beam in
      the highly nonlocal limit. To adjust the relative weight between the two
      nonlinear responses, we employ two distinct wavelengths, inside and outside the
      absorption band of the dye, respectively. Different concentrations of the dye are
      considered in order to enhance the thermal effect. The theoretical analysis is
      complemented by numerical simulations in the highly nonlocal approximation based
      on a semi-analytic approach. Theoretical results are finally compared to
      experimental results in the Nematic Liquid Crystals (NLC) 4-trans-4'-n
      hexylcyclohexylisothiocyanatobenzene (6CHBT) doped with Sudan Blue dye.

PMID- 29347251
TI  - Dynamically crowded solutions of infinitely thin Brownian needles.
AB  - We study the dynamics of solutions of infinitely thin needles up to densities
      deep in the semidilute regime by Brownian dynamics simulations. For high
      densities, these solutions become strongly entangled and the motion of a needle
      is essentially restricted to a one-dimensional sliding in a confining tube
      composed of neighboring needles. From the density-dependent behavior of the
      orientational and translational diffusion, we extract the long-time transport
      coefficients and the geometry of the confining tube. The sliding motion within
      the tube becomes visible in the non-Gaussian parameter of the translational
      motion as an extended plateau at intermediate times and in the intermediate
      scattering function as an algebraic decay. This transient dynamic arrest is also
      corroborated by the local exponent of the mean-square displacements perpendicular
      to the needle axis. Moreover, the probability distribution of the displacements
      perpendicular to the needle becomes strongly non-Gaussian; rather, it displays an
      exponential distribution for large displacements. On the other hand, based on the
      analysis of higher-order correlations of the orientation we find that the
      rotational motion becomes diffusive again for strong confinement. At coarse
      grained time and length scales, the spatiotemporal dynamics of the needle for the
      high entanglement is captured by a single freely diffusing phantom needle with
      long-time transport coefficients obtained from the needle in solution. The time
      dependent dynamics of the phantom needle is also assessed analytically in terms
      of spheroidal wave functions. The dynamic behavior of the needle in solution is
      found to be identical to needle Lorentz systems, where a tracer needle explores a
      quenched disordered array of other needles.

PMID- 29347252
TI  - de Almeida-Thouless instability in short-range Ising spin glasses.
AB  - We use high-temperature series expansions to study the +/-J Ising spin glass in a
      magnetic field in d-dimensional hypercubic lattices for d=5-8 and in the infinite
      range Sherrington-Kirkpatrick (SK) model. The expansions are obtained in the
      variable w=tanh^{2}J/T for arbitrary values of u=tanh^{2}h/T complete to order
      w^{10}. We find that the scaling dimension Delta associated with the ordering
      field h^{2} equals 2 in the SK model and for d>=6. However, in agreement with the
      work of Fisher and Sompolinsky [Phys. Rev. Lett. 54, 1063 (1985)PRLTAO0031
      900710.1103/PhysRevLett.54.1063], there is a violation of scaling in a finite
      field, leading to an anomalous h-T dependence of the de Almeida-Thouless (AT) [J.
      Phys. A 11, 983 (1978)JPHAC50305-447010.1088/0305-4470/11/5/028] line in high
      dimensions, whereas scaling is restored as d->6. Within the convergence of our
      series analysis, we present evidence supporting an AT line in d>=6. In d=5, the
      exponents gamma and Delta are substantially larger than mean-field values, but we
      do not see clear evidence for the AT line in d=5.

PMID- 29347253
TI  - Consistent lattice Boltzmann modeling of low-speed isothermal flows at finite
      Knudsen numbers in slip-flow regime: Application to plane boundaries.
AB  - The first nonequilibrium effect experienced by gaseous flows in contact with
      solid surfaces is the slip-flow regime. While the classical hydrodynamic
      description holds valid in bulk, at boundaries the fluid-wall interactions must
      consider slip. In comparison to the standard no-slip Dirichlet condition, the
      case of slip formulates as a Robin-type condition for the fluid tangential
      velocity. This makes its numerical modeling a challenging task, particularly in
      complex geometries. In this work, this issue is handled with the lattice
      Boltzmann method (LBM), motivated by the similarities between the closure
      relations of the reflection-type boundary schemes equipping the LBM equation and
      the slip velocity condition established by slip-flow theory. Based on this
      analogy, we derive, as central result, the structure of the LBM boundary closure
      relation that is consistent with the second-order slip velocity condition,
      applicable to planar walls. Subsequently, three tasks are performed. First, we
      clarify the limitations of existing slip velocity LBM schemes, based on discrete
      analogs of kinetic theory fluid-wall interaction models. Second, we present
      improved slip velocity LBM boundary schemes, constructed directly at discrete
      level, by extending the multireflection framework to the slip-flow regime. Here,
      two classes of slip velocity LBM boundary schemes are considered: (i) linear slip
      schemes, which are local but retain some calibration requirements and/or
      operation limitations, (ii) parabolic slip schemes, which use a two-point
      implementation but guarantee the consistent prescription of the intended slip
      velocity condition, at arbitrary plane wall discretizations, further dispensing
      any numerical calibration procedure. Third and final, we verify the improvements
      of our proposed slip velocity LBM boundary schemes against existing ones. The
      numerical tests evaluate the ability of the slip schemes to exactly accommodate
      the steady Poiseuille channel flow solution, over distinct wall slippage
      conditions, namely, no-slip, first-order slip, and second-order slip. The
      modeling of channel walls is discussed at both lattice-aligned and non-mesh
      aligned configurations: the first case illustrates the numerical slip due to the
      incorrect modeling of slippage coefficients, whereas the second case adds the
      effect of spurious boundary layers created by the deficient accommodation of bulk
      solution. Finally, the slip-flow solutions predicted by LBM schemes are further
      evaluated for the Knudsen's paradox problem. As conclusion, this work establishes
      the parabolic accuracy of slip velocity schemes as the necessary condition for
      the consistent LBM modeling of the slip-flow regime.

PMID- 29347254
TI  - Fragmentation approach to the point-island model with hindered aggregation:
      Accessing the barrier energy.
AB  - We study the effect of hindered aggregation on the island formation process in a
      one- (1D) and two-dimensional (2D) point-island model for epitaxial growth with
      arbitrary critical nucleus size i. In our model, the attachment of monomers to
      preexisting islands is hindered by an additional attachment barrier,
      characterized by length l_{a}. For l_{a}=0 the islands behave as perfect sinks
      while for l_{a}->infinity they behave as reflecting boundaries. For intermediate
      values of l_{a}, the system exhibits a crossover between two different kinds of
      processes, diffusion-limited aggregation and attachment-limited aggregation. We
      calculate the growth exponents of the density of islands and monomers for the low
      coverage and aggregation regimes. The capture-zone (CZ) distributions are also
      calculated for different values of i and l_{a}. In order to obtain a good spatial
      description of the nucleation process, we propose a fragmentation model, which is
      based on an approximate description of nucleation inside of the gaps for 1D and
      the CZs for 2D. In both cases, the nucleation is described by using two different
      physically rooted probabilities, which are related with the microscopic
      parameters of the model (i and l_{a}). We test our analytical model with
      extensive numerical simulations and previously established results. The proposed
      model describes excellently the statistical behavior of the system for arbitrary
      values of l_{a} and i=1, 2, and 3.

PMID- 29347255
TI  - From Kardar-Parisi-Zhang scaling to explosive desynchronization in arrays of
      limit-cycle oscillators.
AB  - Phase oscillator lattices subject to noise are one of the most fundamental
      systems in nonequilibrium physics. We have discovered a dynamical transition
      which has a significant impact on the synchronization dynamics in such lattices,
      as it leads to an explosive increase of the phase diffusion rate by orders of
      magnitude. Our analysis is based on the widely applicable Kuramoto-Sakaguchi
      model, with local couplings between oscillators. For one-dimensional lattices, we
      observe the universal evolution of the phase spread that is suggested by a
      connection to the theory of surface growth, as described by the Kardar-Parisi
      Zhang (KPZ) model. Moreover, we are able to explain the dynamical transition both
      in one and two dimensions by connecting it to an apparent finite-time singularity
      in a related KPZ lattice model. Our findings have direct consequences for the
      frequency stability of coupled oscillator lattices.

PMID- 29347256
TI  - Self-assembly processes of superparamagnetic colloids in a quasi-two-dimensional
      system.
AB  - Superparamagnetic colloids gather depending on the magnitude of the magnetic
      field applied, forming chains and ribbons in a quasi-two-dimensional chamber. The
      results presented in this work are in good agreement with recent experimental
      multistable data for the mean length of the aggregates in thermodynamic
      equilibrium.

PMID- 29347257
TI  - Nonuniversality in the erosion of tilted landscapes.
AB  - The anisotropic model for landscapes erosion proposed by Pastor-Satorras and
      Rothman [R. Pastor-Satorras and D. H. Rothman, Phys. Rev. Lett. 80, 4349
      (1998)PRLTAO0031-900710.1103/PhysRevLett.80.4349] is believed to capture the
      physics of erosion at intermediate length scale (?3 km), and to account for the
      large value of the roughness exponent alpha observed in real data at this scale.
      Our study of this model-conducted using the nonperturbative renormalization group
      concludes on the nonuniversality of this exponent because of the existence of a
      line of fixed points. Thus the roughness exponent depends (weakly) on the details
      of the soil and the erosion mechanisms. We conjecture that this feature, while
      preserving the generic scaling observed in real data, could explain the wide
      spectrum of values of alpha measured for natural landscapes.

PMID- 29347258
TI  - Doubly excited pulse waves on thin liquid films flowing down an inclined plane:
      An experimental and numerical study.
AB  - The interaction patterns between doubly excited pulse waves on thin liquid films
      flowing down an inclined plane are studied both experimentally and numerically.
      The effect of varying the film flow rate, interpulse interval, and substrate
      inclination angle on the pulse interaction patterns is examined. Our results show
      that different interaction patterns exist for these binary pulses, which include
      solitary wave behavior, partial or complete pulse coalescence, and pulse
      noncoalescence. A regime map of these patterns is plotted for each inclination
      angle examined, parametrized by the film Reynolds number and interpulse interval.
      Finally, the individual effect of the system parameters mentioned above on the
      coalescence distance of binary pulses in the "complete pulse coalescence" mode is
      studied; the results are compared to numerical simulations of the two-dimensional
      Navier-Stokes equations yielding good agreement.

PMID- 29347259
TI  - Electro-osmosis of nematic liquid crystals under weak anchoring and second-order
      surface effects.
AB  - Advent of nematic liquid crystal flows has attracted renewed attention in view of
      microfluidic transport phenomena. Among various transport processes, electro
      osmosis stands as one of the efficient flow actuation mechanisms through narrow
      confinements. In the present study, we explore the electrically actuated flow of
      an ordered nematic fluid with ionic inclusions, taking into account the
      influences from surface-induced elasticity and electrical double layer (EDL)
      phenomena. Toward this, we devise the coupled flow governing equations from
      fundamental free-energy analysis, considering the contributions from first- and
      second-order elastic, dielectric, flexoelectric, charged surface polarization,
      ionic and entropic energies. The present study focuses on the influence of
      surface charge and elasticity effects in the resulting linear electro-osmosis
      through a slit-type microchannel whose surfaces are chemically treated to display
      a homeotropic-type weak anchoring state. An optical periodic stripe configuration
      of the nematic director has been observed, especially for higher electric fields,
      wherein the Ericksen number for the dynamic study is restricted to the order of
      unity. Contrary to the isotropic electrolytes, the EDL potential in this case was
      found to be dependent on the external field strength. Through a systematic
      investigation, we brought out the fact that the wavelength of the oscillating
      patterns is dictated mainly by the external field, while the amplitude depends on
      most of the physical variables ranging from the anchoring strength and the
      flexoelectric coefficients to the surface charge density and electrical double
      layer thickness.

PMID- 29347260
TI  - Enhancement of polar anchoring strength in a graphene-nematic suspension and its
      effect on nematic electro-optic switching.
AB  - A small quantity of monolayer graphene flakes is doped in a nematic liquid
      crystal (LC), and the effective polar anchoring strength coefficient between the
      LC and the alignment substrate is found to increase by an order of magnitude. The
      hexagonal pattern of graphene can interact with the LC's benzene rings via pi-pi
      electron stacking, enabling the LC to anchor to the graphene surface
      homogeneously (i.e., planar anchoring). When the LC cell is filled with the
      graphene-doped LC, some graphene flakes are preferentially attached to the
      alignment layer and modify the substrate's anchoring property. These
      spontaneously deposited graphene flakes promote planar anchoring at the substrate
      and the polar anchoring energy at alignment layer is enhanced significantly. The
      enhanced anchoring energy is found to impact favorably on the electro-optic
      response of the LC. Additional studies reveal that the nematic electro-optic
      switching is significantly faster in the LC-graphene hybrid than that of the pure
      LC.

PMID- 29347261
TI  - Light propagation in binary kagome ribbons with evolving disorder.
AB  - By introducing evolving disorder in the binary kagome ribbons, we study the
      establishment of diffusive spreading of flat band states characterized by
      diffractionless propagation in regular periodic ribbons. Our numerical analysis
      relies on controlling strength and rate of change of disorder during light
      propagation while tailoring binarism of the kagome ribbons in order to isolate
      the flat band with the gap from the rest of the ribbon's eigenvalue spectrum and
      study systematically its influence on diffusion. We show that the flat band plays
      a dominant role in the establishment of the diffusion for a given strength and
      rate of change of disorder, whereas the rest of the ribbon's eigenvalue spectrum
      induces only quantitative differences in the light spreading regimes. Due to the
      universality of studied phenomena, our findings may be of interest in various
      disordered physical systems with flat spectral bands, ranging from photonics to
      ultracold matter systems and plasmonics.

PMID- 29347262
TI  - Dynamics of a bilayer membrane coupled to a two-dimensional cytoskeleton: Scale
      transfers of membrane deformations.
AB  - We theoretically investigate the dynamics of a floating lipid bilayer membrane
      coupled with a two-dimensional cytoskeleton network, taking into account
      explicitly the intermonolayer friction, the discrete lattice structure of the
      cytoskeleton, and its prestress. The lattice structure breaks lateral continuous
      translational symmetry and couples Fourier modes with different wave vectors. It
      is shown that within a short time interval a long-wavelength deformation excites
      a collection of modes with wavelengths shorter than the lattice spacing. These
      modes relax slowly with a common renormalized rate originating from the long
      wavelength mode. As a result, and because of the prestress, the slowest
      relaxation is governed by the intermonolayer friction. Conversely, and most
      interestingly, forces applied at the scale of the cytoskeleton for a sufficiently
      long time can cooperatively excite large-scale modes.

PMID- 29347263
TI  - Modulated phases in a three-dimensional Maier-Saupe model with competing
      interactions.
AB  - This work is dedicated to the study of the discrete version of the Maier-Saupe
      model in the presence of competing interactions. The competition between
      interactions favoring different orientational ordering produces a rich phase
      diagram including modulated phases. Using a mean-field approach and Monte Carlo
      simulations, we show that the proposed model exhibits isotropic and nematic
      phases and also a series of modulated phases that meet at a multicritical point,
      a Lifshitz point. Though the Monte Carlo and mean-field phase diagrams show some
      quantitative disagreements, the Monte Carlo simulations corroborate the general
      behavior found within the mean-field approximation.

PMID- 29347264
TI  - Statistical mechanics of stochastic growth phenomena.
AB  - We develop statistical mechanics for stochastic growth processes and apply it to
      Laplacian growth by using its remarkable connection with a random matrix theory.
      The Laplacian growth equation is obtained from the variation principle and
      describes adiabatic (quasistatic) thermodynamic processes in the two-dimensional
      Dyson gas. By using Einstein's theory of thermodynamic fluctuations we consider
      transitional probabilities between thermodynamic states, which are in a one-to
      one correspondence with simply connected domains occupied by gas. Transitions
      between these domains are described by the stochastic Laplacian growth equation,
      while the transitional probabilities coincide with a free-particle propagator on
      an infinite-dimensional complex manifold with a Kahler metric.

PMID- 29347265
TI  - Coarsening with nontrivial in-domain dynamics: Correlations and interface
      fluctuations.
AB  - Using numerical simulations we investigate the space-time properties of a system
      in which spirals emerge within coarsening domains, thus giving rise to nontrivial
      internal dynamics. Initially proposed in the context of population dynamics, the
      studied six-species model exhibits growing domains composed of three species in a
      rock-paper-scissors relationship. Through the investigation of different
      quantities, such as space-time correlations and the derived characteristic
      length, autocorrelation, density of empty sites, and interface width, we
      demonstrate that the nontrivial dynamics inside the domains affects the
      coarsening process as well as the properties of the interfaces separating
      different domains. Domain growth, aging, and interface fluctuations are shown to
      be governed by exponents whose values differ from those expected in systems with
      curvature driven coarsening.

PMID- 29347266
TI  - Phase separation and folding in swelled nematoelastic films.
AB  - We explore reshaping of nematoelastic films upon imbibing an isotropic solvent
      under conditions when isotropic and nematic phases coexist. The structure of the
      interphase boundary is computed taking into account the optimal nematic
      orientation governed by interaction of gradients of the nematic order parameter
      and solvent concentration. This structure determines the effective line tension
      of the boundary. We further compute equilibrium shapes of deformed thin sheets
      and cylindrical and spherical shells with the rectilinear or circular shape of
      the boundary between nematic and isotropic domains. A differential expansion or
      contraction near this boundary generates a folding pattern spreading out into the
      bulk of both phases. The hierarchical ordering of this pattern is most pronounced
      on a cylindrical shell.

PMID- 29347267
TI  - Decomposition of conditional probability for high-order symbolic Markov chains.
AB  - The main goal of this paper is to develop an estimate for the conditional
      probability function of random stationary ergodic symbolic sequences with
      elements belonging to a finite alphabet. We elaborate on a decomposition
      procedure for the conditional probability function of sequences considered to be
      high-order Markov chains. We represent the conditional probability function as
      the sum of multilinear memory function monomials of different orders (from zero
      up to the chain order). This allows us to introduce a family of Markov chain
      models and to construct artificial sequences via a method of successive
      iterations, taking into account at each step increasingly high correlations among
      random elements. At weak correlations, the memory functions are uniquely
      expressed in terms of the high-order symbolic correlation functions. The proposed
      method fills the gap between two approaches, namely the likelihood estimation and
      the additive Markov chains. The obtained results may have applications for
      sequential approximation of artificial neural network training.

PMID- 29347268
TI  - Nonequilibrium fluctuations during diffusion in liquid layers.
AB  - Theoretical analysis and experiments have provided compelling evidence of the
      presence of long-range nonequilibrium concentration fluctuations during diffusion
      processes in fluids. In this paper, we investigate the dependence of the features
      of the fluctuations from the dimensionality of the system. In three-dimensional
      fluids the amplitude of nonequilibrium fluctuations can become several orders of
      magnitude larger than that of equilibrium fluctuations. Notwithstanding that, the
      amplitude of nonequilibrium fluctuations remains small with respect to the
      concentration difference driving the diffusion process. By extending the theory
      to two-dimensional systems, such as liquid monolayers and bilayers, we show that
      the amplitude of the fluctuations becomes much stronger than in three-dimensional
      systems. We investigate the properties of the fronts of diffusion and show that
      they have a self-affine structure characterized by a Hurst exponent H=1. We
      discuss the implications of these results for diffusion in liquid crystals and in
      cellular membranes of living organisms.

PMID- 29347269
TI  - Length of excitable knots.
AB  - In this paper, we present extensive numerical simulations of an excitable medium
      to study the long-term dynamics of knotted vortex strings for all torus knots up
      to crossing number 11. We demonstrate that FitzHugh-Nagumo evolution preserves
      the knot topology for all the examples presented, thereby providing a field
      theory approach to the study of knots. Furthermore, the evolution yields a well
      defined minimal length for each knot that is comparable to the ropelength of
      ideal knots. We highlight the role of the medium boundary in stabilizing the
      length of the knot and discuss the implications beyond torus knots. We also show
      that there is not a unique attractor within a given knot topology.

PMID- 29347270
TI  - Detection of nonstationary transition to synchronized states of a neural network
      using recurrence analyses.
AB  - We study the stability of asymptotic states displayed by a complex neural
      network. We focus on the loss of stability of a stationary state of networks
      using recurrence quantifiers as tools to diagnose local and global stabilities as
      well as the multistability of a coupled neural network. Numerical simulations of
      a neural network composed of 1024 neurons in a small-world connection scheme are
      performed using the model of Braun et al. [Int. J. Bifurcation Chaos 08, 881
      (1998)IJBEE40218-127410.1142/S0218127498000681], which is a modified model from
      the Hodgkin-Huxley model [J. Phys. 117, 500 (1952)]. To validate the analyses,
      the results are compared with those produced by Kuramoto's order parameter
      [Chemical Oscillations, Waves, and Turbulence (Springer-Verlag, Berlin
      Heidelberg, 1984)]. We show that recurrence tools making use of just integrated
      signals provided by the networks, such as local field potential (LFP) (LFP
      signals) or mean field values bring new results on the understanding of neural
      behavior occurring before the synchronization states. In particular we show the
      occurrence of different stationary and nonstationarity asymptotic states.

PMID- 29347271
TI  - Machine-learning approach for local classification of crystalline structures in
      multiphase systems.
AB  - Machine learning is one of the most popular fields in computer science and has a
      vast number of applications. In this work we will propose a method that will use
      a neural network to locally identify crystal structures in a mixed phase Yukawa
      system consisting of fcc, hcp, and bcc clusters and disordered particles similar
      to plasma crystals. We compare our approach to already used methods and show that
      the quality of identification increases significantly. The technique works very
      well for highly disturbed lattices and shows a flexible and robust way to
      classify crystalline structures that can be used by only providing particle
      positions. This leads to insights into highly disturbed crystalline structures.

PMID- 29347272
TI  - Nonadiabatic dynamics of the excited states for the Lipkin-Meshkov-Glick model.
AB  - We theoretically investigate the impact of the excited state quantum phase
      transition on the adiabatic dynamics for the Lipkin-Meshkov-Glick model. Using a
      time-dependent protocol, we continuously change a model parameter and then
      discuss the scaling properties of the system especially close to the excited
      state quantum phase transition where we find that these depend on the energy
      eigenstate. On top, we show that the mean-field dynamics with the time-dependent
      protocol gives the correct scaling and expectation values in the thermodynamic
      limit even for the excited states.

PMID- 29347273
TI  - Additive scaling law for structural organization of chromatin in chicken
      erythrocyte nuclei.
AB  - Small-angle neutron scattering (SANS) on nuclei of chicken erythrocytes
      demonstrates the cubic dependence of the scattering intensity Q^{-3} in the range
      of momentum transfer Q?10^{-3}-10^{-2}nm^{-1}. Independent spin-echo SANS
      measurements give the spin-echo function, which is well described by the
      exponential law in a range of sizes (3*10^{2})-(3*10^{4}) nm. Both experimental
      dependences reflect the nature of the structural organization of chromatin in the
      nucleus of a living cell, which corresponds to the correlation function
      gamma(r)=ln(xi/r) for r<xi, where xi=(3.69+/-0.07)*10^{3} nm, the size of the
      nucleus. It has the specific scaling property of the logarithmic fractal
      gamma(r/a)=gamma(r)+ln(a), i.e., the scaling down by a gives an additive constant
      to the correlation function, which distinguishes it from the mass fractal, which
      is characterized by multiplicative constant.

PMID- 29347274
TI  - Coupling of lipid membrane elasticity and in-plane dynamics.
AB  - Biomembranes exhibit liquid and solid features concomitantly with their in-plane
      fluidity and elasticity tightly regulated by cells. Here, we present experimental
      evidence supporting the existence of the dynamics-elasticity correlations for
      lipid membranes and propose a mechanism involving molecular packing densities to
      explain them. This paper thereby unifies, at the molecular level, the aspects of
      the continuum mechanics long used to model the two membrane features. This
      ultimately may elucidate the universal physical principles governing the cellular
      phenomena involving biomembranes.

PMID- 29347275
TI  - Physical insight into the thermodynamic uncertainty relation using Brownian
      motion in tilted periodic potentials.
AB  - Using Brownian motion in periodic potentials V(x) tilted by a force f, we provide
      physical insight into the thermodynamic uncertainty relation, a recently
      conjectured principle for statistical errors and irreversible heat dissipation in
      nonequilibrium steady states. According to the relation, nonequilibrium output
      generated from dissipative processes necessarily incurs an energetic cost or heat
      dissipation q, and in order to limit the output fluctuation within a relative
      uncertainty epsilon, at least 2k_{B}T/epsilon^{2} of heat must be dissipated. Our
      model shows that this bound is attained not only at near-equilibrium [f?V^{'}(x)]
      but also at far-from-equilibrium [f?V^{'}(x)], more generally when the dissipated
      heat is normally distributed. Furthermore, the energetic cost is maximized near
      the critical force when the barrier separating the potential wells is about to
      vanish and the fluctuation of Brownian particles is maximized. These findings
      indicate that the deviation of heat distribution from Gaussianity gives rise to
      the inequality of the uncertainty relation, further clarifying the meaning of the
      uncertainty relation. Our derivation of the uncertainty relation also recognizes
      a bound of nonequilibrium fluctuations that the variance of dissipated heat
      (sigma_{q}^{2}) increases with its mean (MU_{q}), and it cannot be smaller than
      2k_{B}TMU_{q}.

PMID- 29347276
TI  - Generalized network modeling: Network extraction as a coarse-scale discretization
      of the void space of porous media.
AB  - A generalized network extraction workflow is developed for parameterizing three
      dimensional (3D) images of porous media. The aim of this workflow is to reduce
      the uncertainties in conventional network modeling predictions introduced due to
      the oversimplification of complex pore geometries encountered in natural porous
      media. The generalized network serves as a coarse discretization of the surface
      generated from a medial-axis transformation of the 3D image. This discretization
      divides the void space into individual pores and then subdivides each pore into
      sub-elements called half-throat connections. Each half-throat connection is
      further segmented into corners by analyzing the medial axis curves of its axial
      plane. The parameters approximating each corner-corner angle, volume, and
      conductivity-are extracted at different discretization levels, corresponding to
      different wetting layer thickness and local capillary pressures during multiphase
      flow simulations. Conductivities are calculated using direct single-phase flow
      simulation so that the network can reproduce the single-phase flow permeability
      of the underlying image exactly. We first validate the algorithm by using it to
      discretize synthetic angular pore geometries and show that the network model
      reproduces the corner angles accurately. We then extract network models from
      micro-CT images of porous rocks and show that the network extraction preserves
      macroscopic properties, the permeability and formation factor, and the statistics
      of the micro-CT images.

PMID- 29347277
TI  - Towards uncovering the structure of power fluctuations of wind farms.
AB  - The structure of the turbulence-driven power fluctuations in a wind farm is
      fundamentally described from basic concepts. A derived tuning-free model,
      supported with experiments, reveals the underlying spectral content of the power
      fluctuations of a wind farm. It contains two power-law trends and oscillations in
      the relatively low- and high-frequency ranges. The former is mostly due to the
      turbulent interaction between the flow and the turbine properties, whereas the
      latter is due to the advection between turbine pairs. The spectral wind-farm
      scale power fluctuations Phi_{P} exhibit a power-law decay proportional to f^{
      5/3-2} in the region corresponding to the turbulence inertial subrange and at
      relatively large scales, Phi_{P}~f^{-2}. Due to the advection and turbulent
      diffusion of large-scale structures, a spectral oscillation exists with the
      product of a sinusoidal behavior and an exponential decay in the frequency
      domain.

PMID- 29347278
TI  - Modes of failure in disordered solids.
AB  - The two principal ingredients determining the failure modes of disordered solids
      are the strength of heterogeneity and the length scale of the region affected in
      the solid following a local failure. While the latter facilitates damage
      nucleation, the former leads to diffused damage-the two extreme natures of the
      failure modes. In this study, using the random fiber bundle model as a prototype
      for disordered solids, we classify all failure modes that are the results of
      interplay between these two effects. We obtain scaling criteria for the different
      modes and propose a general phase diagram that provides a framework for
      understanding previous theoretical and experimental attempts of interpolation
      between these modes. As the fiber bundle model is a long-standing model for
      interpreting various features of stressed disordered solids, the general phase
      diagram can serve as a guiding principle in anticipating the responses of
      disordered solids in general.

PMID- 29347279
TI  - Narrow log-periodic modulations in non-Markovian random walks.
AB  - What are the necessary ingredients for log-periodicity to appear in the dynamics
      of a random walk model? Can they be subtle enough to be overlooked? Previous
      studies suggest that long-range damaged memory and negative feedback together are
      necessary conditions for the emergence of log-periodic oscillations. The role of
      negative feedback would then be crucial, forcing the system to change direction.
      In this paper we show that small-amplitude log-periodic oscillations can emerge
      when the system is driven by positive feedback. Due to their very small
      amplitude, these oscillations can easily be mistaken for numerical finite-size
      effects. The models we use consist of discrete-time random walks with strong
      memory correlations where the decision process is taken from memory profiles
      based either on a binomial distribution or on a delta distribution. Anomalous
      superdiffusive behavior and log-periodic modulations are shown to arise in the
      large time limit for convenient choices of the models parameters.

PMID- 29347280
TI  - Interactions in reentrant phase behavior of a charged nanoparticle solution by
      multivalent ions.
AB  - The interactions following a reentrant phase transition of charged silica
      nanoparticles from one phase to two phases and back to one phase by varying the
      concentration of multivalent counterions have been examined. The observations are
      far beyond the framework of Debye-Huckel or even nonlinear Poisson-Boltzmann
      equations and demonstrate the universal behavior of multivalent counterion-driven
      charge inversion. We show that the interplay of multivalent counterion-induced
      short-range attraction and long-range electrostatic repulsion between
      nanoparticles results in reentrant phase behavior.

PMID- 29347281
TI  - Coherent wave transmission in quasi-one-dimensional systems with Levy disorder.
AB  - We study the random fluctuations of the transmission in disordered quasi-one
      dimensional systems such as disordered waveguides and/or quantum wires whose
      random configurations of disorder are characterized by density distributions with
      a long tail known as Levy distributions. The presence of Levy disorder leads to
      large fluctuations of the transmission and anomalous localization, in relation to
      the standard exponential localization (Anderson localization). We calculate the
      complete distribution of the transmission fluctuations for a different number of
      transmission channels in the presence and absence of time-reversal symmetry.
      Significant differences in the transmission statistics between disordered systems
      with Anderson and anomalous localizations are revealed. The theoretical
      predictions are independently confirmed by tight-binding numerical simulations.

PMID- 29347282
TI  - Site-bond percolation of heteronuclear dimers irreversibly deposited on square
      lattices.
AB  - A generalization of the site-bond percolation problem was studied, in which pairs
      of neighboring sites (site dimers) and bonds are occupied irreversibly, randomly,
      and independently on homogeneous square surfaces. A dimer is composed of two
      segments and occupies two adjacent sites. Each segment can be either a conductive
      segment (segment type A) or a nonconductive segment (segment type B). Two types
      of dimers are considered, AA and AB, and the connectivity analysis is carried out
      by accounting only for the conductive segments (segments type A) in combination
      with bonds. For the combination of dimers and bonds, two different criteria were
      analyzed: the union or the intersection between the adsorbed percolating
      particles and the bonds. By means of numerical simulations and finite-size
      scaling analysis, the complete phase diagram separating a percolating from a non
      percolating region was determined.

PMID- 29347283
TI  - Stochastic wave-function unravelling of the generalized Lindblad equation.
AB  - We investigate generalized non-Markovian stochastic Schrodinger equations (SSEs),
      driven by a multidimensional counting process and multidimensional Brownian
      motion introduced by A. Barchielli and C. Pellegrini [J. Math. Phys. 51, 112104
      (2010)JMAPAQ0022-248810.1063/1.3514539]. We show that these SSEs can be
      translated in a nonlinear form, which can be efficiently simulated. The
      simulation is illustrated by the model of a two-level system in a structured
      bath, and the results of the simulations are compared with the exact solution of
      the generalized master equation.

PMID- 29347284
TI  - Two-point resistances in an Apollonian network.
AB  - The computation of resistance between two nodes in a resistor network is a
      classical problem in electric theory and graph theory. Based on the Apollonian
      packing, Andrade et al. introduced a deterministic growing type of networks A(k)
      [Phys. Rev. Lett. 94, 018702 (2005)PRLTAO0031-900710.1103/PhysRevLett.94.018702].
      In this paper, first, a recursive algorithm for computing resistance between any
      two nodes in A(k) is given. Then as explanations, using the algorithm, explicit
      expressions for some resistances in A(k) are obtained.

PMID- 29347285
TI  - Erratum: Phase diagram of fluid phases in ^{3}He-^{4}He mixtures [Phys. Rev. E
      91, 022138 (2015)].
AB  - This corrects the article DOI: 10.1103/PhysRevE.91.022138.

PMID- 29347286
TI  - Influence of topology in the mobility enhancement of pulse-coupled oscillator
      synchronization.
AB  - In this work we revisit the nonmonotonic behavior (NMB) of synchronization time
      with velocity reported for systems of mobile pulse-coupled oscillators (PCOs). We
      devise a control parameter that allows us to predict in which range of velocities
      NMB may occur, also uncovering the conditions allowing us to establish the
      emergence of NMB based on specific features of the connectivity rule.
      Specifically, our results show that if the connectivity rule is such that the
      interaction patterns are sparse and, more importantly, include a large fraction
      of nonreciprocal interactions, then the system will display NMB. We furthermore
      provide a microscopic explanation relating the presence of such features of the
      connectivity patterns to the existence of local clusters unable to synchronize,
      termed frustrated clusters, for which we also give a precise definition in terms
      of simple graph concepts. We conclude that, if the probability of finding a
      frustrated cluster in a system of moving PCOs is high enough, NMB occurs in a
      predictable range of velocities.

PMID- 29347287
TI  - Solution of the Riemann problem for polarization waves in a two-component Bose
      Einstein condensate.
AB  - We provide a classification of the possible flows of two-component Bose-Einstein
      condensates evolving from initially discontinuous profiles. We consider the
      situation where the dynamics can be reduced to the consideration of a single
      polarization mode (also denoted as "magnetic excitation") obeying a system of
      equations equivalent to the Landau-Lifshitz equation for an easy-plane
      ferromagnet. We present the full set of one-phase periodic solutions. The
      corresponding Whitham modulation equations are obtained together with formulas
      connecting their solutions with the Riemann invariants of the modulation
      equations. The problem is not genuinely nonlinear, and this results in a non
      single-valued mapping of the solutions of the Whitham equations with physical
      wave patterns as well as the appearance of interesting elements-contact
      dispersive shock waves-that are absent in more standard, genuinely nonlinear
      situations. Our analytic results are confirmed by numerical simulations.

PMID- 29347288
TI  - Optical band gap in a cholesteric elastomer doped by metallic nanospheres.
AB  - We analyzed the optical band gaps for axially propagating electromagnetic waves
      throughout a metallic doped cholesteric elastomer. The composed medium is made of
      metallic nanospheres (silver) randomly dispersed in a cholesteric elastomer
      liquid crystal whose dielectric properties can be represented by a resonant
      effective uniaxial tensor. We found that the band gap properties of the periodic
      system greatly depend on the volume fraction of nanoparticles in the cholesteric
      elastomer. In particular, we observed a displacement of the reflection band for
      quite small fraction volumes whereas for larger values of this fraction there
      appears a secondary band in the higher frequency region. We also have calculated
      the transmittance and reflectance spectra for our system. These calculations
      verify the mentioned band structure and provide additional information about the
      polarization features of the radiation.

PMID- 29347289
TI  - Quasimonochromatic exact solutions to Maxwell's equations with finite total
      energy and arbitrary frequencies in the vacuum.
AB  - We analyze a family of exact finite energy solutions to Maxwell's equations.
      These solutions are a subset of the modified-power-spectrum solutions found by
      Ziolkowski [Phys. Rev. A 39, 2005 (1989)10.1103/PhysRevA.39.2005]. There are
      three characteristic parameters in the solutions: q_{1},q_{2}, and k_{0}. q_{1}
      and q_{2} are related to the frequency bandwidth of the solution. In the
      parameter space of k_{0}q_{1}?1 and k_{0}q_{2}?1, they represent
      quasimonochromatic continuous wave fields with the main angular frequency k_{0}c
      and energy localized in the transverse directions. Under the restriction of
      q_{1}?q_{2}, the beam propagates mainly in the +z direction with velocity c and
      limited diffraction.

PMID- 29347290
TI  - Turbulent transport and mixing in transitional Rayleigh-Taylor unstable flow: A
      priori assessment of gradient-diffusion and similarity modeling.
AB  - Data from a 1152*760*1280 direct numerical simulation [N. J. Mueschke and O.
      Schilling, Phys. Fluids 21, 014106 (2009)PHFLE61070-663110.1063/1.3064120] of a
      Rayleigh-Taylor mixing layer modeled after a small-Atwood-number water-channel
      experiment is used to investigate the validity of gradient diffusion and
      similarity closures a priori. The budgets of the mean flow, turbulent kinetic
      energy, turbulent kinetic energy dissipation rate, heavy-fluid mass fraction
      variance, and heavy-fluid mass fraction variance dissipation rate transport
      equations across the mixing layer were previously analyzed [O. Schilling and N.
      J. Mueschke, Phys. Fluids 22, 105102 (2010)PHFLE61070-663110.1063/1.3484247] at
      different evolution times to identify the most important transport and mixing
      mechanisms. Here a methodology is introduced to systematically estimate model
      coefficients as a function of time in the closures of the dynamically significant
      terms in the transport equations by minimizing the L_{2} norm of the difference
      between the model and correlations constructed using the simulation data. It is
      shown that gradient-diffusion and similarity closures used for the turbulent
      kinetic energy K, turbulent kinetic energy dissipation rate epsilon, heavy-fluid
      mass fraction variance S, and heavy-fluid mass fraction variance dissipation rate
      chi equations capture the shape of the exact, unclosed profiles well over the
      nonlinear and turbulent evolution regimes. Using order-of-magnitude estimates [O.
      Schilling and N. J. Mueschke, Phys. Fluids 22, 105102 (2010)PHFLE61070
      663110.1063/1.3484247] for the terms in the exact transport equations and their
      closure models, it is shown that several of the standard closures for the
      turbulent production and dissipation (destruction) must be modified to include
      Reynolds-number scalings appropriate for Rayleigh-Taylor flow at small to
      intermediate Reynolds numbers. The late-time, large Reynolds number coefficients
      are determined to be different from those used in shear flow applications and
      largely adopted in two-equation Reynolds-averaged Navier-Stokes (RANS) models of
      Rayleigh-Taylor turbulent mixing. In addition, it is shown that the predictions
      of the Boussinesq model for the Reynolds stress agree better with the data when
      additional buoyancy-related terms are included. It is shown that an unsteady RANS
      paradigm is needed to predict the transitional flow dynamics from early evolution
      times, analogous to the small Reynolds number modifications in RANS models of
      wall-bounded flows in which the production-to-dissipation ratio is far from
      equilibrium. Although the present study is specific to one particular flow and
      one set of initial conditions, the methodology could be applied to calibrations
      of other Rayleigh-Taylor flows with different initial conditions (which may give
      different results during the early-time, transitional flow stages, and perhaps
      asymptotic stage). The implications of these findings for developing high
      fidelity eddy viscosity-based turbulent transport and mixing models of Rayleigh
      Taylor turbulence are discussed.

PMID- 29347291
TI  - Dynamics of a flexible ferromagnetic filament in a rotating magnetic field.
AB  - Flexible magnetic filaments have garnered considerable attention as prospective
      materials for the creation of different microdevices. We describe a theoretical
      model of a ferromagnetic filament and derive its equations of motion by
      variational techniques. The numerical algorithm used to solve the filament
      dynamics in magnetic fields of different configurations is described. It is found
      that in a rotating field the filament transitions between synchronous and
      asynchronous regimes with respect to the rotating field, similarly to a rigid
      magnetic dipole. The mean angular velocity of the filament is well described by a
      relation valid for a rigid magnetic dipole with quantitative differences
      attributable to the flexibility of the filament.

PMID- 29347292
TI  - Boundary conditions for a one-sided numerical model of evaporative instabilities
      in sessile drops of ethanol on heated substrates.
AB  - The work is focused on obtaining boundary conditions for a one-sided numerical
      model of thermoconvective instabilities in evaporating pinned sessile droplets of
      ethanol on heated substrates. In the one-sided model, appropriate boundary
      conditions for heat and mass transfer equations are required at the droplet
      surface. Such boundary conditions are obtained in the present work based on a
      derived semiempirical theoretical formula for the total droplet's evaporation
      rate, and on a two-parametric nonisothermal approximation of the local
      evaporation flux. The main purpose of these boundary conditions is to be applied
      in future three-dimensional (3D) one-sided numerical models in order to save a
      lot of computational time and resources by solving equations only in the droplet
      domain. Two parameters, needed for the nonisothermal approximation of the local
      evaporation flux, are obtained by fitting computational results of a 2D two-sided
      numerical model. Such model is validated here against parabolic flight
      experiments and the theoretical value of the total evaporation rate. This study
      combines theoretical, experimental, and computational approaches in convective
      evaporation of sessile droplets. The influence of the gravity level on
      evaporation rate and contributions of different mechanisms of vapor transport
      (diffusion, Stefan flow, natural convection) are shown. The qualitative
      difference (in terms of developing thermoconvective instabilities) between steady
      state and unsteady numerical approaches is demonstrated.

PMID- 29347293
TI  - Shear-banding and superdiffusivity in entangled polymer solutions.
AB  - Using high-resolution confocal rheometry, we study the shear profiles of well
      entangled DNA solutions under large-amplitude oscillatory shear in a rectilinear
      planar shear cell. With increasing Weissenberg number (Wi), we observe successive
      transitions from normal Newtonian linear shear profiles to wall-slip dominant
      shear profiles and, finally, to shear-banding profiles at high Wi. To investigate
      the microscopic origin of the observed shear banding, we study the dynamics of
      micron-sized tracers embedded in DNA solutions. Surprisingly, tracer particles in
      the shear frame exhibit transient superdiffusivity and strong dynamic
      heterogeneity. The probability distribution functions of particle displacements
      follow a power-law scaling at large displacements, indicating a Levy-walk-type
      motion, reminiscent of tracer dynamics in entangled wormlike micelle solutions
      and sheared colloidal glasses. We further characterize the length and time scales
      associated with the abnormal dynamics of tracer particles. We hypothesize that
      the unusual particle dynamics arise from localized shear-induced chain
      disentanglement.

PMID- 29347294
TI  - ^{13}C NMR study of the director distribution adopted by the modulated nematic
      phases formed by liquid-crystal dimers with odd numbers of atoms in their
      spacers.
AB  - The orientational order of the molecules in the bent mesogen CB6OCB has been
      studied throughout the range of temperature stability of both the N_{U} and
      N_{TB} liquid-crystal phases by ^{13}C NMR spectroscopy. These spectra provide
      local order parameters for the para axes of both of the nonequivalent
      cyanobiphenyl groups and show how they change on entering the twist-bend nematic
      phase. A key feature of the order parameters is a weak, but clear maximum in the
      temperature variation of the order parameter prior to the N_{TB} phase. This
      suggests that the directors in both the N_{U} and N_{TB} phases are tilted with
      respect to the magnetic field of the spectrometer. Significantly the
      conformational states of the spacer are comparable in both phases, although the
      low temperature nematic is chiral but not that at high temperature. It is
      proposed that the higher temperature, tilted phase could be the splay-bend
      nematic phase.

PMID- 29347295
TI  - Time-varying multiplex network: Intralayer and interlayer synchronization.
AB  - A large class of engineered and natural systems, ranging from transportation
      networks to neuronal networks, are best represented by multiplex network
      architectures, namely a network composed of two or more different layers where
      the mutual interaction in each layer may differ from other layers. Here we
      consider a multiplex network where the intralayer coupling interactions are
      switched stochastically with a characteristic frequency. We explore the
      intralayer and interlayer synchronization of such a time-varying multiplex
      network. We find that the analytically derived necessary condition for intralayer
      and interlayer synchronization, obtained by the master stability function
      approach, is in excellent agreement with our numerical results. Interestingly, we
      clearly find that the higher frequency of switching links in the layers enhances
      both intralayer and interlayer synchrony, yielding larger windows of
      synchronization. Further, we quantify the resilience of synchronous states
      against random perturbations, using a global stability measure based on the
      concept of basin stability, and this reveals that intralayer coupling strength is
      most crucial for determining both intralayer and interlayer synchrony. Lastly, we
      investigate the robustness of interlayer synchronization against a progressive
      demultiplexing of the multiplex structure, and we find that for rapid switching
      of intralayer links, the interlayer synchronization persists even when a large
      number of interlayer nodes are disconnected.

PMID- 29347296
TI  - Temperature dependence of the nonlinear optical response of smectic liquid
      crystals containing gold nanorods.
AB  - The present study is devoted to the investigation of the nonlinear optical
      properties of a smectic liquid crystal doped with gold nanorods. Using the Z-scan
      technique, we investigate the changes in the optical birefringence of a
      homeotropic sample upon laser exposure, considering the configurations of normal
      and oblique incidence. Our results reveal that the birefringence variations may
      be governed by distinct physical mechanisms, depending on the relative angle
      between the far-field director and the wave vector of the excitation laser beam.
      In particular, we observe that the position dependence of the far-field
      transmittance exhibits different behaviors as the incidence angle is changed,
      indicating that distortions in the beam wavefront may be associated with the
      thermal lens phenomenon or an optically induced reorientation of the nematic
      director. The temperature dependence of the nonlinear refractive and absorptive
      coefficients is investigated close to the smectic-A-nematic phase transition. A
      detailed analysis of the interplay between smectic order and plasmon resonance is
      performed, thus unveiling the capability of plasmonic liquid crystal to be used
      in optical devices.

PMID- 29347297
TI  - Intermittent direction reversals of moving spatially localized turbulence
      observed in two-dimensional Kolmogorov flow.
AB  - We have found that in two-dimensional Kolmogorov flow a spatially localized
      turbulent state (SLT) exists stably and travels with a constant speed on average
      switching the moving direction randomly and intermittently for moderate values of
      the control parameters: Reynolds number and the flow rate. We define the coarse
      grained position and velocity of an SLT and separate the motion of the SLT from
      its internal turbulent dynamics by introducing a co-moving frame. The switching
      process of an SLT represented by the coarse-grained velocity seems to be a random
      telegraph signal. Focusing on the asymmetry of the internal turbulence we
      introduce two coarse-grained variables characterizing the internal dynamics.
      These quantities follow the switching process reasonably. This suggests that the
      twin attracting invariant sets each of which corresponds to a one-way traveling
      SLT are embedded in the attractor of the moving SLT and the connection of the two
      sets is too complicated to be represented by a few degrees of freedom but the
      motion of an SLT is correlated with the internal turbulent dynamics.

PMID- 29347298
TI  - Self-induced temperature gradients in Brownian dynamics.
AB  - Brownian systems often surmount energy barriers by absorbing and emitting heat to
      and from their local environment. Usually, the temperature gradients created by
      this heat exchange are assumed to dissipate instantaneously. Here we relax this
      assumption to consider the case where Brownian dynamics on a time-independent
      potential can lead to self-induced temperature gradients. In the same way that
      externally imposed temperature gradients can cause directed motion, these self
      induced gradients affect the dynamics of the Brownian system. The result is a
      coupling between the local environment and the Brownian subsystem. We explore the
      resulting dynamics and thermodynamics of these coupled systems and develop a
      robust method for numerical simulation. In particular, by focusing on one
      dimensional situations, we show that self-induced temperature gradients reduce
      barrier-crossing rates. We also consider a heat engine and a heat pump based on
      temperature gradients induced by a Brownian system in a nonequilibrium potential.

PMID- 29347299
TI  - Self-similarity in explosive synchronization of complex networks.
AB  - We report that explosive synchronization of networked oscillators (a process
      through which the transition to coherence occurs without intermediate stages but
      is rather characterized by a sudden and abrupt jump from the network's
      asynchronous to synchronous motion) is related to self-similarity of synchronous
      clusters of different size. Self-similarity is revealed by destructing the
      network synchronous state during the backward transition and observed with the
      decrease of the coupling strength between the nodes of the network. As
      illustrative examples, networks of Kuramoto oscillators with different topologies
      of links have been considered. For each one of such topologies, the destruction
      of the synchronous state goes step by step with self-similar configurations of
      interacting oscillators. At the critical point, the invariance of the phase
      distribution in the synchronized cluster with respect to the cluster size is
      reported.

PMID- 29347300
TI  - Swimming efficiency in a shear-thinning fluid.
AB  - Micro-organisms expend energy moving through complex media. While propulsion
      speed is an important property of locomotion, efficiency is another factor that
      may determine the swimming gait adopted by a micro-organism in order to locomote
      in an energetically favorable manner. The efficiency of swimming in a Newtonian
      fluid is well characterized for different biological and artificial swimmers.
      However, these swimmers often encounter biological fluids displaying shear
      thinning viscosities. Little is known about how this nonlinear rheology
      influences the efficiency of locomotion. Does the shear-thinning rheology render
      swimming more efficient or less? How does the swimming efficiency depend on the
      propulsion mechanism of a swimmer and rheological properties of the surrounding
      shear-thinning fluid? In this work, we address these fundamental questions on the
      efficiency of locomotion in a shear-thinning fluid by considering the squirmer
      model as a general locomotion model to represent different types of swimmers. Our
      analysis reveals how the choice of surface velocity distribution on a squirmer
      may reduce or enhance the swimming efficiency. We determine optimal shear rates
      at which the swimming efficiency can be substantially enhanced compared with the
      Newtonian case. The nontrivial variations of swimming efficiency prompt questions
      on how micro-organisms may tune their swimming gaits to exploit the shear
      thinning rheology. The findings also provide insights into how artificial
      swimmers should be designed to move through complex media efficiently.

PMID- 29347301
TI  - Critical behavior of the two-dimensional icosahedron model.
AB  - In the context of a discrete analog of the classical Heisenberg model, we
      investigate the critical behavior of the icosahedron model, where the interaction
      energy is defined as the inner product of neighboring vector spins of unit length
      pointing to the vertices of the icosahedron. The effective correlation length and
      magnetization of the model are calculated by means of the corner-transfer-matrix
      renormalization group (CTMRG) method. A scaling analysis with respect to the
      cutoff dimension m in CTMRG reveals a second-order phase transition characterized
      by the exponents nu=1.62+/-0.02 and beta=0.12+/-0.01. We also extract the central
      charge from the classical analog of entanglement entropy as c=1.90+/-0.02, which
      cannot be explained by the minimal series of conformal field theory.

PMID- 29347302
TI  - Dynamics of washboard road formation driven by a harmonic oscillator.
AB  - Granular surfaces subjected to repeated passage often spontaneously develop a
      corrugated pattern. In this study, we scrutinized the growth dynamics of surface
      corrugation in a self-rotating sand bed that is traced by the edge of a
      vertically oscillating arm. We found that both the rotation velocity and the
      frequency of the oscillator strongly affect the occurrence rate of corrugation as
      well as the time evolution in the corrugation pattern, due to the intermittent
      collision between the oscillator and sand bed. We also discovered that the growth
      dynamics involves two distinct collective modes that describe the translational
      motion of the corrugation pattern on the sand bed.

PMID- 29347303
TI  - Predicting tensorial electrophoretic effects in asymmetric colloids.
AB  - We formulate a numerical method for predicting the tensorial linear response of a
      rigid, asymmetrically charged body to an applied electric field. This prediction
      requires calculating the response of the fluid to the Stokes drag forces on the
      moving body and on the countercharges near its surface. To determine the fluid's
      motion, we represent both the body and the countercharges using many point
      sources of drag known as Stokeslets. Finding the correct flow field amounts to
      finding the set of drag forces on the Stokeslets that is consistent with the
      relative velocities experienced by each Stokeslet. The method rigorously
      satisfies the condition that the object moves with no transfer of momentum to the
      fluid. We demonstrate that a sphere represented by 1999 well-separated Stokeslets
      on its surface produces flow and drag force like a solid sphere to 1% accuracy.
      We show that a uniformly charged sphere with 3998 body and countercharge
      Stokeslets obeys the Smoluchowski prediction [F. Morrison, J. Colloid Interface
      Sci. 34, 210 (1970)JCISA50021-979710.1016/0021-9797(70)90171-2] for
      electrophoretic mobility when the countercharges lie close to the sphere. Spheres
      with dipolar and quadrupolar charge distributions rotate and translate as
      predicted analytically to 4% accuracy or better. We describe how the method can
      treat general asymmetric shapes and charge distributions. This method offers
      promise as a way to characterize and manipulate asymmetrically charged colloid
      scale objects from biology (e.g., viruses) and technology (e.g., self-assembled
      clusters).

PMID- 29347304
TI  - Convex hulls of random walks in higher dimensions: A large-deviation study.
AB  - The distribution of the hypervolume V and surface ?V of convex hulls of
      (multiple) random walks in higher dimensions are determined numerically,
      especially containing probabilities far smaller than P=10^{-1000} to estimate
      large deviation properties. For arbitrary dimensions and large walk lengths T, we
      suggest a scaling behavior of the distribution with the length of the walk T
      similar to the two-dimensional case and behavior of the distributions in the
      tails. We underpin both with numerical data in d=3 and d=4 dimensions. Further,
      we confirm the analytically known means of those distributions and calculate
      their variances for large T.

PMID- 29347305
TI  - Antiswarming: Structure and dynamics of repulsive chemically active particles.
AB  - Chemically active Brownian particles with surface catalytic reactions may repel
      each other due to diffusiophoretic interactions in the reaction and product
      concentration fields. The system behavior can be described by a "chemical"
      coupling parameter Gamma_{c} that compares the strength of diffusiophoretic
      repulsion to Brownian motion, and by a mapping to the classical electrostatic one
      component plasma (OCP) system. When confined to a constant-volume domain, body
      centered cubic (bcc) crystals spontaneously form from random initial
      configurations when the repulsion is strong enough to overcome Brownian motion.
      Face-centered cubic (fcc) crystals may also be stable. The "melting point" of the
      "liquid-to-crystal transition" occurs at Gamma_{c}~140 for both bcc and fcc
      lattices.

PMID- 29347306
TI  - Logarithmic scaling for fluctuations of a scalar concentration in wall
      turbulence.
AB  - Within wall turbulence, there is a sublayer where the mean velocity and the
      variance of velocity fluctuations vary logarithmically with the height from the
      wall. This logarithmic scaling is also known for the mean concentration of a
      passive scalar. By using heat as such a scalar in a laboratory experiment of a
      turbulent boundary layer, the existence of the logarithmic scaling is shown here
      for the variance of fluctuations of the scalar concentration. It is reproduced by
      a model of energy-containing eddies that are attached to the wall.

PMID- 29347307
TI  - Dynamics of nonspherical microbubble oscillations above instability threshold.
AB  - Time-resolved dynamics of nonspherical oscillations of micrometer-sized bubbles
      are captured and analyzed using high-speed imaging. The axisymmetry of the bubble
      shape is ensured with certainty for the first time from the recordings of two
      synchronous high-speed cameras located at 90^{?}. The temporal dynamics of finite
      amplitude nonspherical oscillations are then analyzed for various acoustic
      pressures above the instability threshold. The experimental results are compared
      with recent theories accounting for nonlinearities and mode coupling,
      highlighting particular effects inherent to these mechanisms (saturation of the
      instability, triggering of nonparametric shape modes). Finally, the amplitude of
      the nonspherical oscillations is given as function of the driving pressure both
      for quadrupolar and octupolar bubbles.

PMID- 29347308
TI  - Clogging of soft particles in two-dimensional hoppers.
AB  - Using experiments and simulations, we study the flow of soft particles through
      quasi-two-dimensional hoppers. The first experiment uses oil-in-water emulsion
      droplets in a thin sample chamber. Due to surfactants coating the droplets, they
      easily slide past each other, approximating soft frictionless disks. For these
      droplets, clogging at the hopper exit requires a narrow hopper opening only
      slightly larger than the droplet diameter. The second experiment uses soft
      hydrogel particles in a thin sample chamber, where we vary gravity by changing
      the tilt angle of the chamber. For reduced gravity, clogging becomes easier and
      can occur for larger hopper openings. Our simulations mimic the emulsion
      experiments and demonstrate that softness is a key factor controlling clogging:
      with stiffer particles or a weaker gravitational force, clogging is easier. The
      fractional amount a single particle is deformed under its own weight is a useful
      parameter measuring particle softness. Data from the simulation and hydrogel
      experiments collapse when compared using this parameter. Our results suggest that
      prior studies using hard particles were in a limit where the role of softness is
      negligible, which causes clogging to occur with significantly larger openings.

PMID- 29347309
TI  - Permutation entropy with vector embedding delays.
AB  - Permutation entropy (PE) is a statistic used widely for the detection of
      structure within a time series. Embedding delay times at which the PE is reduced
      are characteristic timescales for which such structure exists. Here, a
      generalized scheme is investigated where embedding delays are represented by
      vectors rather than scalars, permitting PE to be calculated over a (D-1)
      dimensional space, where D is the embedding dimension. This scheme is applied to
      numerically generated noise, sine wave and logistic map series, and experimental
      data sets taken from a vertical-cavity surface emitting laser exhibiting
      temporally localized pulse structures within the round-trip time of the laser
      cavity. Results are visualized as PE maps as a function of embedding delay, with
      low PE values indicating combinations of embedding delays where correlation
      structure is present. It is demonstrated that vector embedding delays enable
      identification of structure that is ambiguous or masked, when the embedding delay
      is constrained to scalar form.

PMID- 29347310
TI  - Quantum heat engine with coupled superconducting resonators.
AB  - We propose a quantum heat engine composed of two superconducting transmission
      line resonators interacting with each other via an optomechanical-like coupling.
      One resonator is periodically excited by a thermal pump. The incoherently driven
      resonator induces coherent oscillations in the other one due to the coupling. A
      limit cycle, indicating finite power output, emerges in the thermodynamical phase
      space. The system implements an all-electrical analog of a photonic piston.
      Instead of mechanical motion, the power output is obtained as a coherent
      electrical charging in our case. We explore the differences between the quantum
      and classical descriptions of our system by solving the quantum master equation
      and classical Langevin equations. Specifically, we calculate the mean number of
      excitations, second-order coherence, as well as the entropy, temperature, power,
      and mean energy to reveal the signatures of quantum behavior in the statistical
      and thermodynamic properties of the system. We find evidence of a quantum
      enhancement in the power output of the engine at low temperatures.

PMID- 29347311
TI  - Percolation thresholds and fractal dimensions for square and cubic lattices with
      long-range correlated defects.
AB  - We study long-range power-law correlated disorder on square and cubic lattices.
      In particular, we present high-precision results for the percolation thresholds
      and the fractal dimension of the largest clusters as a function of the
      correlation strength. The correlations are generated using a discrete version of
      the Fourier filtering method. We consider two different metrics to set the length
      scales over which the correlations decay, showing that the percolation thresholds
      are highly sensitive to such system details. By contrast, we verify that the
      fractal dimension d_{f} is a universal quantity and unaffected by the choice of
      metric. We also show that for weak correlations, its value coincides with that
      for the uncorrelated system. In two dimensions we observe a clear increase of the
      fractal dimension with increasing correlation strength, approaching d_{f}->2. The
      onset of this change does not seem to be determined by the extended Harris
      criterion.

PMID- 29347312
TI  - Experimental investigation of water distribution in a two-phase zone during
      gravity-dominated evaporation.
AB  - We characterize the water repartition within the partially saturated (two-phase)
      zone (PSZ) during evaporation from mixed wettable porous media by controlling the
      wettability of glass beads, their sizes, and as well the surrounding relative
      humidity. Here, capillary numbers are low and under these conditions, the
      percolating front is stabilized by gravity. Using experimental and numerical
      analyses, we find that the PSZ saturation decreases with the Bond number, where
      packing of smaller particles have higher saturation values than packing made of
      larger particles. Results also reveal that the extent (height) of the PSZ, as
      well as water saturation in the PSZ, both increase with wettability. We also
      numerically calculate the saturation exclusively contained in connected liquid
      films and results show that values are less than the expected PSZ saturation.
      These results strongly reflect that the two-phase zone is not solely made up of
      connected capillary networks but also made of disconnected water clusters or
      pockets. Moreover, we also find that global saturation (PSZ + full wet zone)
      decreases with wettability, confirming that greater quantity of water is lost via
      evaporation with increasing hydrophilicity. These results show that connected
      liquid films are favored in more-hydrophilic systems while disconnected water
      pockets are favored in less-hydrophilic systems.

PMID- 29347313
TI  - Exact mean-energy expansion of Ginibre's gas for coupling constants
      Gamma=2*(oddinteger).
AB  - Using the approach of a Vandermonde determinant to the power Gamma=Q^{2}/k_{B}T
      expansion on monomial functions, a way to find the excess energy U_{exc} of the
      two-dimensional one-component plasma (2DOCP) on hard and soft disks (or a Dyson
      gas) for odd values of Gamma/2 is provided. At Gamma=2, the present study not
      only corroborates the result for the particle-particle energy contribution of the
      Dyson gas found by Shakirov [Shakirov, Phys. Lett. A 375, 984
      (2011)10.1016/j.physleta.2011.01.004] by using an alternative approach, but also
      provides the exact N-finite expansion of the excess energy of the 2DOCP on the
      hard disk. The excess energy is fitted to the ansatz of the form
      U_{exc}=K^{1}N+K^{2}sqrt[N]+K^{3}+K^{4}/N+O(1/N^{2}) to study the finite-size
      correction, with K^{i} coefficients and N the number of particles. In particular,
      the bulk term of the excess energy is in agreement with the well known result of
      Jancovici for the hard disk in the thermodynamic limit [Jancovici, Phys. Rev.
      Lett. 46, 386 (1981)10.1103/PhysRevLett.46.386]. Finally, an expression is found
      for the pair correlation function which still keeps a link with the random matrix
      theory via the kernel in the Ginibre ensemble [Ginibre, J. Math. Phys. 6, 440
      (1965)10.1063/1.1704292] for odd values of Gamma/2. A comparison between the
      analytical two-body density function and histograms obtained with Monte Carlo
      simulations for small systems and Gamma=2,6,10,... shows that the approach
      described in this paper may be used to study analytically the crossover behavior
      from systems in the fluid phase to small crystals.

PMID- 29347314
TI  - Polymer adsorption on curved surfaces.
AB  - The conformational behavior of a coarse-grained finite polymer chain near an
      attractive spherical surface was investigated by means of multicanonical Monte
      Carlo computer simulations. In a detailed analysis of canonical equilibrium data
      over a wide range of sphere radius and temperature, we have constructed entire
      phase diagrams both for nongrafted and end-grafted polymers. For the
      identification of the conformational phases, we have calculated several energetic
      and structural observables such as gyration tensor based shape parameters and
      their fluctuations by canonical statistical analysis. Despite the simplicity of
      our model, it qualitatively represents in the considered parameter range real
      systems that are studied in experiments. The work discussed here could have
      experimental implications from protein-ligand interactions to designing nanosmart
      materials.

PMID- 29347315
TI  - Impact of anticipation in dynamical systems.
AB  - Many animals, including humans, have predictive capabilities and, presumably,
      base their behavioral decisions-at least partially-upon an anticipated state of
      their environment. We explore a minimal version of this idea in the context of
      particles that interact according to a pairwise potential. Anticipation enters
      the picture by calculating the interparticle forces from linear extrapolations of
      the particle positions some time tau in the future. Simulations show that for
      intermediate values of tau, compared to a transient time scale defined by the
      potential and the initial conditions, the particles form rotating clusters in
      which the particles are arranged in a hexagonal pattern. Analysis of the system
      shows that anticipation induces energy dissipation and we show that the kinetic
      energy asymptotically decays as 1/t. Furthermore, we show that the angular
      momentum is not necessarily conserved for tau>0, and that asymmetries in the
      initial condition therefore can cause rotational movement. These results suggest
      that anticipation could play an important role in collective behavior, since it
      may induce pattern formation and stabilizes the dynamics of the system.

PMID- 29347316
TI  - Quantum and classical complexity in coupled maps.
AB  - We study a generic and paradigmatic two-degrees-of-freedom system consisting of
      two coupled perturbed cat maps with different types of dynamics. The Wigner
      separability entropy (WSE)-equivalent to the operator space entanglement entropy
      and the classical separability entropy (CSE) are used as measures of complexity.
      For the case where both degrees of freedom are hyperbolic, the maps are
      classically ergodic and the WSE and the CSE behave similarly, growing to higher
      values than in the doubly elliptic case. However, when one map is elliptic and
      the other hyperbolic, the WSE reaches the same asymptotic value than that of the
      doubly hyperbolic case but at a much slower rate. The CSE only follows the WSE
      for a few map steps, revealing that classical dynamical features are not enough
      to explain complexity growth.

PMID- 29347317
TI  - Onset of fractional-order thermal convection in porous media.
AB  - The macroscopic description of buoyancy-driven thermal convection in porous media
      is governed by advection-diffusion processes, which in the presence of
      thermophysical heterogeneities fail to predict the onset of thermal convection
      and the average rate of heat transfer. This work extends the classical model of
      heat transfer in porous media by including a fractional-order advective
      dispersive term to account for the role of thermophysical heterogeneities in
      shifting the thermal instability point. The proposed fractional-order model
      overcomes limitations of the common closure approaches for the thermal dispersion
      term by replacing the diffusive assumption with a fractional-order model. Through
      a linear stability analysis and Galerkin procedure, we derive an analytical
      formula for the critical Rayleigh number as a function of the fractional model
      parameters. The resulting critical Rayleigh number reduces to the classical value
      in the absence of thermophysical heterogeneities when solid and fluid phases have
      similar thermal conductivities. Numerical simulations of the coupled flow
      equation with the fractional-order energy model near the primary bifurcation
      point confirm our analytical results. Moreover, data from pore-scale simulations
      are used to examine the potential of the proposed fractional-order model in
      predicting the amount of heat transfer across the porous enclosure. The linear
      stability and numerical results show that, unlike the classical thermal advection
      dispersion models, the fractional-order model captures the advance and delay in
      the onset of convection in porous media and provides correct scalings for the
      average heat transfer in a thermophysically heterogeneous medium.

PMID- 29347318
TI  - Entropy production in systems with random transition rates close to equilibrium.
AB  - We study the entropy production of systems out of equilibrium using random
      networks. We focus on systems with a finite number of states described by a
      master equation close to equilibrium. The dynamics are mapped into a network of
      states (nodes) connected by transition rates (links). Using this framework, we
      analyze the entropy production of ensembles of randomly generated networks owing
      to specific constraints (e.g., size or symmetries) and identify the most
      important parameters that determine its value. This analysis gives a null-model
      estimation for the entropy production that can be used for comparison with
      specific systems.

PMID- 29347319
TI  - Electromagnetic-radiation absorption by water.
AB  - Why does a microwave oven work? How does biological tissue absorb electromagnetic
      radiation? Astonishingly, we do not have a definite answer to these simple
      questions because the microscopic processes governing the absorption of
      electromagnetic waves by water are largely unclarified. This absorption can be
      quantified by dielectric loss spectra, which reveal a huge peak at a frequency of
      the exciting electric field of about 20 GHz and a gradual tailing off toward
      higher frequencies. The microscopic interpretation of such spectra is highly
      controversial and various superpositions of relaxation and resonance processes
      ascribed to single-molecule or molecule-cluster motions have been proposed for
      their analysis. By combining dielectric, microwave, THz, and far-infrared
      spectroscopy, here we provide nearly continuous temperature-dependent broadband
      spectra of water. Moreover, we find that corresponding spectra for aqueous
      solutions reveal the same features as pure water. However, in contrast to the
      latter, crystallization in these solutions can be avoided by supercooling. As
      different spectral contributions tend to disentangle at low temperatures, this
      enables us to deconvolute them when approaching the glass transition under
      cooling. We find that the overall spectral development, including the 20 GHz
      feature (employed for microwave heating), closely resembles the behavior known
      for common supercooled liquids. Thus water's absorption of electromagnetic waves
      at room temperature is not unusual but very similar to that of glass-forming
      liquids at elevated temperatures, deep in the low-viscosity liquid regime, and
      should be interpreted along similar lines.

PMID- 29347320
TI  - Neural field model of memory-guided search.
AB  - Many organisms can remember locations they have previously visited during a
      search. Visual search experiments have shown exploration is guided away from
      these locations, reducing redundancies in the search path before finding a hidden
      target. We develop and analyze a two-layer neural field model that encodes
      positional information during a search task. A position-encoding layer sustains a
      bump attractor corresponding to the searching agent's current location, and
      search is modeled by velocity input that propagates the bump. A memory layer
      sustains persistent activity bounded by a wave front, whose edges expand in
      response to excitatory input from the position layer. Search can then be biased
      in response to remembered locations, influencing velocity inputs to the position
      layer. Asymptotic techniques are used to reduce the dynamics of our model to a
      low-dimensional system of equations that track the bump position and front
      boundary. Performance is compared for different target-finding tasks.

PMID- 29347321
TI  - Analytical solutions for the profile of two-dimensional droplets with finite
      length precursor films.
AB  - By means of the lubrication approximation we obtain the full family of static
      bidimensional profiles of a liquid resting on a substrate under partial-wetting
      conditions imposed by a disjoining-conjoining pressure. We show that for a set of
      quite general disjoining-conjoining pressure potentials, the free surface can
      adopt only five nontrivial static patterns; in particular, we find solutions when
      the height goes to zero which describe satisfactorily the complete free surface
      for a finite amount of fluid deposited on a substrate. To test the extension of
      the applicability of our solutions, we compare them with those obtained when the
      lubrication approximations are not employed and under conditions where the
      lubrication hypothesis are not strictly valid, and also with axisymmetric
      solutions. For a given disjoining-conjoining potential, we report a new
      analytical solution that accounts for all the five possible solutions.

PMID- 29347322
TI  - Typical equilibrium state of an embedded quantum system.
AB  - We consider an arbitrary quantum system coupled nonperturbatively to a large
      arbitrary and fully quantum environment. In the work by Ithier and Benaych
      Georges [Phys. Rev. A 96, 012108 (2017)2469-992610.1103/PhysRevA.96.012108] the
      typicality of the dynamics of such an embedded quantum system was established for
      several classes of random interactions. In other words, the time evolution of its
      quantum state does not depend on the microscopic details of the interaction.
      Focusing on the long-time regime, we use this property to calculate analytically
      a partition function characterizing the stationary state and involving the
      overlaps between eigenvectors of a bare and a dressed Hamiltonian. This partition
      function provides a thermodynamical ensemble which includes the microcanonical
      and canonical ensembles as particular cases. We check our predictions with
      numerical simulations.

PMID- 29347323
TI  - Evolution of inverse cascades and formation of precondensate in Gross-Pitaevskii
      turbulence in two dimensions.
AB  - Here we study how coherence appears in a system driven by noise at small scales.
      In the wave turbulence modeled by the Gross-Pitaevskii or the nonlinear
      Schrodinger equation, we observe states with correlation scales smaller than the
      system size but much larger than the excitation scale. We call a such state
      precondensate to distinguish it from condensate defined as a systemwide coherent
      state. Both condensate and precondensate are characterized by large-scale phase
      coherence and a narrow distribution of amplitudes. When one excites small scales,
      precondensate is achieved relatively quickly by an inverse cascade heating
      quasiequilibrium distribution of large-scale modes. The transition from the
      precondensate to the systemwide condensate requires a much longer time. The
      spectra of precondensate differ from quasiequilibrium and are characterized by
      two bending points, one on the scale of the average distance between vortex pairs
      and the other on the scale of the distance between vortices in a pair. We suggest
      temporal evolution laws for both lengths and use them to predict the probability
      of the transition to condensate.

PMID- 29347324
TI  - Exponential integrators in time-dependent density-functional calculations.
AB  - The integrating factor and exponential time differencing methods are implemented
      and tested for solving the time-dependent Kohn-Sham equations. Popular time
      propagation methods used in physics, as well as other robust numerical
      approaches, are compared to these exponential integrator methods in order to
      judge the relative merit of the computational schemes. We determine an
      improvement in accuracy of multiple orders of magnitude when describing dynamics
      driven primarily by a nonlinear potential. For cases of dynamics driven by a time
      dependent external potential, the accuracy of the exponential integrator methods
      are less enhanced but still match or outperform the best of the conventional
      methods tested.

PMID- 29347325
TI  - Two-step relaxation mode analysis with multiple evolution times applied to all
      atom molecular dynamics protein simulation.
AB  - Proteins implement their functionalities when folded into specific three
      dimensional structures, and their functions are related to the protein structures
      and dynamics. Previously, we applied a relaxation mode analysis (RMA) method to
      protein systems; this method approximately estimates the slow relaxation modes
      and times via simulation and enables investigation of the dynamic properties
      underlying the protein structural fluctuations. Recently, two-step RMA with
      multiple evolution times has been proposed and applied to a slightly complex
      homopolymer system, i.e., a single [n]polycatenane. This method can be applied to
      more complex heteropolymer systems, i.e., protein systems, to estimate the
      relaxation modes and times more accurately. In two-step RMA, we first perform RMA
      and obtain rough estimates of the relaxation modes and times. Then, we apply RMA
      with multiple evolution times to a small number of the slowest relaxation modes
      obtained in the previous calculation. Herein, we apply this method to the results
      of principal component analysis (PCA). First, PCA is applied to a 2-MUs molecular
      dynamics simulation of hen egg-white lysozyme in aqueous solution. Then, the two
      step RMA method with multiple evolution times is applied to the obtained
      principal components. The slow relaxation modes and corresponding relaxation
      times for the principal components are much improved by the second RMA.

PMID- 29347326
TI  - Equation of state of polydisperse hard-disk mixtures in the high-density regime.
AB  - A proposal to link the equation of state of a monocomponent hard-disk fluid to
      the equation of state of a polydisperse hard-disk mixture is presented. Event
      driven molecular dynamics simulations are performed to obtain data for the
      compressibility factor of the monocomponent fluid and of 26 polydisperse mixtures
      with different size distributions. Those data are used to assess the proposal and
      to infer the values of the compressibility factor of the monocomponent hard-disk
      fluid in the metastable region from those of mixtures in the high-density region.
      The collapse of the curves for the different mixtures is excellent in the stable
      region. In the metastable regime, except for two mixtures in which
      crystallization is present, the outcome of the approach exhibits a rather good
      performance. The simulation results indicate that a (reduced) variance of the
      size distribution larger than about 0.01 is sufficient to avoid crystallization
      and explore the metastable fluid branch.

PMID- 29347327
TI  - Effective dielectric response of dispersions of graded particles.
AB  - Based upon our compact group approach and the Hashin-Shtrikman variational
      theorem, we propose a solution, which effectively incorporates many-particle
      effects in concentrated systems, to the problem of the effective quasistatic
      permittivity of dispersions of graded dielectric particles. After the theory is
      shown to recover existing analytical results and simulation data for dispersions
      of hard dielectric spheres with power-law permittivity profiles, we use it to
      describe the effective dielectric response of nonconducting polymer-ceramic
      composites modeled as dispersions of dielectric core-shell particles. Possible
      generalizations of the results are specified.

PMID- 29347328
TI  - Chaos and unpredictability in evolution of cooperation in continuous time.
AB  - Cooperators benefit others with paying costs. Evolution of cooperation crucially
      depends on the cost-benefit ratio of cooperation, denoted as c. In this work, we
      investigate the infinitely repeated prisoner's dilemma for various values of c
      with four of the representative memory-one strategies, i.e., unconditional
      cooperation, unconditional defection, tit-for-tat, and win-stay-lose-shift. We
      consider replicator dynamics which deterministically describes how the fraction
      of each strategy evolves over time in an infinite-sized well-mixed population in
      the presence of implementation error and mutation among the four strategies. Our
      finding is that this three-dimensional continuous-time dynamics exhibits chaos
      through a bifurcation sequence similar to that of a logistic map as c varies. If
      mutation occurs with rate MU?1, the position of the bifurcation sequence on the c
      axis is numerically found to scale as MU^{0.1}, and such sensitivity to MU
      suggests that mutation may have nonperturbative effects on evolutionary paths. It
      demonstrates how the microscopic randomness of the mutation process can be
      amplified to macroscopic unpredictability by evolutionary dynamics.

PMID- 29347329
TI  - Unified implicit kinetic scheme for steady multiscale heat transfer based on the
      phonon Boltzmann transport equation.
AB  - An implicit kinetic scheme is proposed to solve the stationary phonon Boltzmann
      transport equation (BTE) for multiscale heat transfer problem. Compared to the
      conventional discrete ordinate method, the present method employs a macroscopic
      equation to accelerate the convergence in the diffusive regime. The macroscopic
      equation can be taken as a moment equation for phonon BTE. The heat flux in the
      macroscopic equation is evaluated from the nonequilibrium distribution function
      in the BTE, while the equilibrium state in BTE is determined by the macroscopic
      equation. These two processes exchange information from different scales, such
      that the method is applicable to the problems with a wide range of Knudsen
      numbers. Implicit discretization is implemented to solve both the macroscopic
      equation and the BTE. In addition, a memory reduction technique, which is
      originally developed for the stationary kinetic equation, is also extended to
      phonon BTE. Numerical comparisons show that the present scheme can predict
      reasonable results both in ballistic and diffusive regimes with high efficiency,
      while the memory requirement is on the same order as solving the Fourier law of
      heat conduction. The excellent agreement with benchmark and the rapid converging
      history prove that the proposed macro-micro coupling is a feasible solution to
      multiscale heat transfer problems.

PMID- 29347330
TI  - Lagrangian formulation and symmetrical description of liquid dynamics.
AB  - Theoretical description of liquids has been primarily based on the hydrodynamic
      approach and its generalization to the solid-like regime. We show that the same
      liquid properties can be derived starting from solid-like equations and
      generalizing them to account for the hydrodynamic flow. Both approaches predict
      propagating shear waves with the notable gap in k-space. This gives an important
      symmetry of liquids regarding their description. We subsequently construct a two
      field Lagrangian of liquid dynamics where the dissipative hydrodynamic and solid
      like terms are treated on equal footing. The Lagrangian predicts two gapped waves
      propagating in opposite space-time directions. The dissipative and mass terms
      compete by promoting gaps in k-space and energy, respectively. When bare mass is
      close to the field hopping frequency, both gaps close and the dissipative term
      annihilates the bare mass.

PMID- 29347331
TI  - Two-dimensional collective electron magnetotransport, oscillations, and chaos in
      a semiconductor superlattice.
AB  - When quantized, traces of classically chaotic single-particle systems include
      eigenvalue statistics and scars in eigenfuntions. Since 2001, many theoretical
      and experimental works have argued that classically chaotic single-electron
      dynamics influences and controls collective electron transport. For transport in
      semiconductor superlattices under tilted magnetic and electric fields, these
      theories rely on a reduction to a one-dimensional self-consistent drift model. A
      two-dimensional theory based on self-consistent Boltzmann transport does not
      support that single-electron chaos influences collective transport. This theory
      agrees with existing experimental evidence of current self-oscillations, predicts
      spontaneous collective chaos via a period doubling scenario, and could be tested
      unambiguously by measuring the electric potential inside the superlattice under a
      tilted magnetic field.

PMID- 29347332
TI  - Linear and nonlinear market correlations: Characterizing financial crises and
      portfolio optimization.
AB  - Pearson correlation and mutual information-based complex networks of the day-to
      day returns of U.S. S&P500 stocks between 1985 and 2015 have been constructed to
      investigate the mutual dependencies of the stocks and their nature. We show that
      both networks detect qualitative differences especially during (recent) turbulent
      market periods, thus indicating strongly fluctuating interconnections between the
      stocks of different companies in changing economic environments. A measure for
      the strength of nonlinear dependencies is derived using surrogate data and leads
      to interesting observations during periods of financial market crises. In
      contrast to the expectation that dependencies reduce mainly to linear
      correlations during crises, we show that (at least in the 2008 crisis) nonlinear
      effects are significantly increasing. It turns out that the concept of centrality
      within a network could potentially be used as some kind of an early warning
      indicator for abnormal market behavior as we demonstrate with the example of the
      2008 subprime mortgage crisis. Finally, we apply a Markowitz mean variance
      portfolio optimization and integrate the measure of nonlinear dependencies to
      scale the investment exposure. This leads to significant outperformance as
      compared to a fully invested portfolio.

PMID- 29347333
TI  - Extending electrostatics of dielectric spheres to arbitrary charge distributions
      with applications to biosystems.
AB  - A previously developed classical model of electrostatic interactions, based on a
      formalism of dielectric spheres, which has been found to have surprising accuracy
      for S state atoms, is extended by allowing higher-order moments of the intrinsic
      charge distribution. Two methods to introduce the charge distribution (point
      moments at the center vs surface charge) are shown to be equivalent and are
      compared with another common model for polarizable atoms that utilizes
      polarizable point dipoles. Unlike the polarizable point dipole model, the
      polarizable spheres models do not suffer from a divergence at small separation of
      atoms and are easily generalized to higher multipoles.

PMID- 29347334
TI  - Sequence selection by dynamical symmetry breaking in an autocatalytic binary
      polymer model.
AB  - Template-directed replication of nucleic acids is at the essence of all living
      beings and a major milestone for any origin of life scenario. We present an
      idealized model of prebiotic sequence replication, where binary polymers act as
      templates for their autocatalytic replication, thereby serving as each others
      reactants and products in an intertwined molecular ecology. Our model
      demonstrates how autocatalysis alters the qualitative and quantitative system
      dynamics in counterintuitive ways. Most notably, numerical simulations reveal a
      very strong intrinsic selection mechanism that favors the appearance of a few
      population structures with highly ordered and repetitive sequence patterns when
      starting from a pool of monomers. We demonstrate both analytically and through
      simulation how this "selection of the dullest" is caused by continued symmetry
      breaking through random fluctuations in the transient dynamics that are amplified
      by autocatalysis and eventually propagate to the population level. The impact of
      these observations on related prebiotic mathematical models is discussed.

PMID- 29347335
TI  - Saturation of entropy production in quantum many-body systems.
AB  - Bridging the second law of thermodynamics and microscopic reversible dynamics has
      been a longstanding problem in statistical physics. Here, we address this problem
      on the basis of quantum many-body physics, and discuss how the entropy production
      saturates in isolated quantum systems under unitary dynamics. First, we
      rigorously prove that the entropy production does indeed saturate in the long
      time regime, even when the total system is in a pure state. Second, we discuss
      the non-negativity of the entropy production at saturation, implying the second
      law of thermodynamics. This is based on the eigenstate thermalization hypothesis,
      which states that even a single energy eigenstate is thermal. We also numerically
      demonstrate that the entropy production saturates at a non-negative value even
      when the initial state of a heat bath is a single energy eigenstate. Our results
      reveal fundamental properties of the entropy production in isolated quantum
      systems at late times.

PMID- 29347336
TI  - Numerical study of two disks settling in an Oldroyd-B fluid: From periodic
      interaction to chaining.
AB  - In this article, we present a numerical study of the dynamics of two disks
      sedimenting in a narrow vertical channel filled with an Oldroyd-B fluid. Two
      kinds of particle dynamics are observed: (i) a periodic interaction between the
      two disks, and (ii) the formation of a two-disk chain. For the periodic
      interaction of the two disks, two different motions are observed: (a) the two
      disks stay far apart and interact periodically, and (b) the two disks interact
      closely and then far apart in a periodic way, like the drafting, kissing, and
      tumbling of two disks sedimenting in a Newtonian fluid, due to a weak elastic
      force. Concerning the formation of a two-disk chain occurring at higher values of
      the elasticity number, either a tilted chain or a vertical chain is observed. Our
      simulations show that, as expected, the values of the elasticity and Mach numbers
      are the determining factors concerning the particle chain formation and its
      orientation.

PMID- 29347337
TI  - Controlling percolation with limited resources.
AB  - Connectivity, or the lack thereof, is crucial for the function of many man-made
      systems, from financial and economic networks over epidemic spreading in social
      networks to technical infrastructure. Often, connections are deliberately
      established or removed to induce, maintain, or destroy global connectivity. Thus,
      there has been a great interest in understanding how to control percolation, the
      transition to large-scale connectivity. Previous work, however, studied control
      strategies assuming unlimited resources. Here, we depart from this unrealistic
      assumption and consider the effect of limited resources on the effectiveness of
      control. We show that, even for scarce resources, percolation can be controlled
      with an efficient intervention strategy. We derive such an efficient strategy and
      study its implications, revealing a discontinuous transition as an unintended
      side effect of optimal control.

PMID- 29347338
TI  - Numerical solution of modified differential equations based on symmetry
      preservation.
AB  - In this paper, we propose a method to construct invariant finite-difference
      schemes for solution of partial differential equations (PDEs) via consideration
      of modified forms of the underlying PDEs. The invariant schemes, which preserve
      Lie symmetries, are obtained based on the method of equivariant moving frames.
      While it is often difficult to construct invariant numerical schemes for PDEs due
      to complicated symmetry groups associated with cumbersome discrete variable
      transformations, we note that symmetries associated with more convenient
      transformations can often be obtained by appropriately modifying the original
      PDEs. In some cases, modifications to the original PDEs are also found to be
      useful in order to avoid trivial solutions that might arise from particular
      selections of moving frames. In our proposed method, modified forms of PDEs can
      be obtained either by addition of perturbation terms to the original PDEs or
      through defect correction procedures. These additional terms, whose primary
      purpose is to enable symmetries with more convenient transformations, are then
      removed from the system by considering moving frames for which these specific
      terms go to zero. Further, we explore selection of appropriate moving frames that
      result in improvement in accuracy of invariant numerical schemes based on
      modified PDEs. The proposed method is tested using the linear advection equation
      (in one- and two-dimensions) and the inviscid Burgers' equation. Results obtained
      for these tests cases indicate that numerical schemes derived from the proposed
      method perform significantly better than existing schemes not only by virtue of
      improvement in numerical accuracy but also due to preservation of qualitative
      properties or symmetries of the underlying differential equations.

PMID- 29347339
TI  - Rheology of dense granular flows for elongated particles.
AB  - We study the rheology of dense granular flows for frictionless spherocylinders by
      means of 3D numerical simulations. As in the case of spherical particles, the
      effective friction MU is an increasing function of the inertial number I, and we
      systematically investigate the dependence of MU on the particle aspect ratio Q,
      as well as that of the normal stress differences, the volume fraction, and the
      coordination number. We show in particular that the quasistatic friction
      coefficient is nonmonotonic with Q: from the spherical case Q=1, it first sharply
      increases, reaches a maximum around Q?1.05, and then gently decreases until Q=3,
      passing its initial value at Q?2. We provide a microscopic interpretation for
      this unexpected behavior through the analysis of the distribution of dissipative
      contacts around the particles: as compared to spheres, slightly elongated grains
      enhance contacts in their central cylindrical band, whereas at larger aspect
      ratios particles tend to align and dissipate by preferential contacts at their
      hemispherical caps.

PMID- 29347340
TI  - Mirror node correlations tuning synchronization in multiplex networks.
AB  - We show that the degree-degree correlations have a major impact on global
      synchronizability (GS) of multiplex networks, enabling the specification of
      synchronizability by only changing the degree-degree correlations of the mirror
      nodes while maintaining the connection architecture of the individual layer
      unaltered. If individual layers have nodes that are mildly correlated, the
      multiplex network is best synchronizable when the mirror degrees are strongly
      negatively correlated. If individual layers have nodes with strong degree-degree
      correlations, mild correlations among the degrees of mirror nodes are the best
      strategy for the optimization of GS. Global synchronization also depend on the
      density of connections, a phenomenon not observed in a single layer network. The
      results are crucial to understand, predict, and specify behavior of systems
      having multiple types of connections among the interacting units.

PMID- 29347341
TI  - Spatial correlations of hydrodynamic fluctuations in simple fluids under shear
      flow: A mesoscale simulation study.
AB  - Hydrodynamic fluctuations in simple fluids under shear flow are demonstrated to
      be spatially correlated, in contrast to the fluctuations at equilibrium, using
      mesoscopic hydrodynamic simulations. The simulation results for the equal-time
      hydrodynamic correlations in a multiparticle collision dynamics (MPC) fluid in
      shear flow are compared with the explicit expressions obtained from fluctuating
      hydrodynamics calculations. For large wave vectors k, the nonequilibrium
      contributions to transverse and longitudinal velocity correlations decay as k^{
      4} for wave vectors along the flow direction and as k^{-2} for the off-flow
      directions. For small wave vectors, a crossover to a slower decay occurs,
      indicating long-range correlations in real space. The coupling between the
      transverse velocity components, which vanishes at equilibrium, also exhibits a
      k^{-2} dependence on the wave vector. In addition, we observe a quadratic
      dependency on the shear rate of the nonequilibrium contribution to pressure.

PMID- 29347342
TI  - Synchronization of coupled active rotators by common noise.
AB  - We study the effect of common noise on coupled active rotators. While such a
      noise always facilitates synchrony, coupling may be attractive (synchronizing) or
      repulsive (desynchronizing). We develop an analytical approach based on a
      transformation to approximate angle-action variables and averaging over fast
      rotations. For identical rotators, we describe a transition from full to partial
      synchrony at a critical value of repulsive coupling. For nonidentical rotators,
      the most nontrivial effect occurs at moderate repulsive coupling, where a
      juxtaposition of phase locking with frequency repulsion (anti-entrainment) is
      observed. We show that the frequency repulsion obeys a nontrivial power law.

PMID- 29347343
TI  - Dissipation, lag, and drift in driven fluctuating systems.
AB  - This work deals with thermostated fluctuating systems subjected to driven
      transformations of the internal energetics. The main focus is on generally
      multidimensional systems with continuous configurational degrees of freedom over
      which overdamped Markovian fluctuations take place (diffusive regime of the
      motion). Mutual bounds are established between the average energy dissipation,
      the deviation between nonequilibrium probability density and underlying
      equilibrium distribution due to the system's lag, and the statistical properties
      of the components of the directed flow induced by the transformation itself. The
      directed flow is here expressed in terms of time-dependent "drift velocity"
      associated with the probability current in a advection-like formulation of the
      nonstationary Fokker-Planck equation. Consideration of the drift makes that the
      bounds achieved here extend the inequality derived by Vaikuntanathan and
      Jarzynski [Europhys. Lett. 87, 60005 (2009)EULEEJ0295-507510.1209/0295
      5075/87/60005] involving only dissipation and lag. The key relations are then
      specified for the so-called stochastic pumps, i.e., systems that reach a periodic
      steady state in response of cyclic transformations and that are prototypes of
      nonautonomous dissipative converters of input energy into directed motion; a one
      dimensional case model is adopted to illustrate the main features. Complementary
      results concerning bounds between the evolution rates of dissipation and lag,
      valid for both overdamped and underdamped dynamics, are also presented.

PMID- 29347344
TI  - Experimental investigation of mesoscopic heterogeneous motion of laser-activated
      self-propelling Janus particles in suspension.
AB  - The mesoscopic collective motion of self-propelling active particle suspension is
      experimentally investigated. The active particles are silica micro spheres with
      Au hemisphere coating, and their propelling strength is activated by laser
      irradiation. The suspension is driven from equilibrium to near equilibrium and
      far from equilibrium by tuning the excitation laser intensity. By use of the long
      term particle tracking technique, the time evolution of a large amount of active
      particles is resolvable. For low laser intensity, the suspension is driven to
      near equilibrium state with homogeneous superdiffusion motion. The strength of
      enhanced superdiffusion is monotonically related to the laser intensity. For high
      laser intensity, the motility-induced phase separation with the coexistence of
      dense cluster and very dilute individual particle are observed. It leads to
      highly heterogeneous dynamic with less mobile jammed cluster and fast-moving
      particles and subsequently suppresses the enhanced superdiffusion. Such
      heterogeneous dynamics is similar to many far from equilibrium systems. Finally,
      the degree away from equilibrium (Gaussian dynamics) triggered by propelling
      strength is quantified by non-Gaussian parameters.

PMID- 29347345
TI  - Effect of temperature on the dynamics and geometry of reactive-wetting interfaces
      around room temperature.
AB  - The temperature effect on the dynamics and geometry of a mercury droplet (~150
      MUm) spreading on a silver substrate (4000 A) was studied. The system temperature
      was controlled by a heating stage in the temperature range of -15  degrees C < T
      < 25  degrees C, and the spreading process was monitored using an optical
      microscope. We studied the wetting dynamics (droplet radius and velocity) as a
      function of temperature. We found that for all studied temperatures, the
      spreading radius R(t) grows linearly with time, with a velocity value depending
      on temperature. We also studied the temperature effect on the kinetic roughening
      properties of the advancing interface (growth (beta) and roughness (alpha)
      exponents). Our results show that the growth exponent increases with temperature
      while the roughness exponent is relatively constant. In addition, we obtained the
      system's activation energy at this temperature range.

PMID- 29347346
TI  - Elucidating distinct ion channel populations on the surface of hippocampal
      neurons via single-particle tracking recurrence analysis.
AB  - Protein and lipid nanodomains are prevalent on the surface of mammalian cells. In
      particular, it has been recently recognized that ion channels assemble into
      surface nanoclusters in the soma of cultured neurons. However, the interactions
      of these molecules with surface nanodomains display a considerable degree of
      heterogeneity. Here, we investigate this heterogeneity and develop statistical
      tools based on the recurrence of individual trajectories to identify
      subpopulations within ion channels in the neuronal surface. We specifically study
      the dynamics of the K^{+} channel Kv1.4 and the Na^{+} channel Nav1.6 on the
      surface of cultured hippocampal neurons at the single-molecule level. We find
      that both these molecules are expressed in two different forms with distinct
      kinetics with regards to surface interactions, emphasizing the complex proteomic
      landscape of the neuronal surface. Further, the tools presented in this work
      provide new methods for the analysis of membrane nanodomains, transient
      confinement, and identification of populations within single-particle
      trajectories.

PMID- 29347347
TI  - Energetics in a model of prebiotic evolution.
AB  - Previously we reported [A. Wynveen et al., Phys. Rev. E 89, 022725
      (2014)PLEEE81539-375510.1103/PhysRevE.89.022725] that requiring that the systems
      regarded as lifelike be out of chemical equilibrium in a model of abstracted
      polymers undergoing ligation and scission first introduced by Kauffman [S. A.
      Kauffman, The Origins of Order (Oxford University Press, New York, 1993), Chap.
      7] implied that lifelike systems were most probable when the reaction network was
      sparse. The model was entirely statistical and took no account of the bond
      energies or other energetic constraints. Here we report results of an extension
      of the model to include effects of a finite bonding energy in the model. We
      studied two conditions: (1) A food set is continuously replenished and the total
      polymer population is constrained but the system is otherwise isolated and (2) in
      addition to the constraints in (1) the system is in contact with a finite
      temperature heat bath. In each case, detailed balance in the dynamics is
      guaranteed during the computations by continuous recomputation of a temperature
      [in case (1)] and of the chemical potential (in both cases) toward which the
      system is driven by the dynamics. In the isolated case, the probability of
      reaching a metastable nonequilibrium state in this model depends significantly on
      the composition of the food set, and the nonequilibrium states satisfying
      lifelike condition turn out to be at energies and particle numbers consistent
      with an equilibrium state at high negative temperature. As a function of the
      sparseness of the reaction network, the lifelike probability is nonmonotonic, as
      in our previous model, but the maximum probability occurs when the network is
      less sparse. In the case of contact with a thermal bath at a positive ambient
      temperature, we identify two types of metastable nonequilibrium states, termed
      locally and thermally alive, and locally dead and thermally alive, and evaluate
      their likelihood of appearance, finding maxima at an optimal temperature and an
      optimal degree of sparseness in the network. We use a Euclidean metric in the
      space of polymer populations to distinguish these states from one another and
      from fully equilibrated states. The metric can be used to characterize the degree
      and type of chemical equilibrium in observed systems, as we illustrate for the
      proteome of the ribosome.

PMID- 29347348
TI  - Consciousness as a global property of brain dynamic activity.
AB  - We seek general principles of the structure of the cellular collective activity
      associated with conscious awareness. Can we obtain evidence for features of the
      optimal brain organization that allows for adequate processing of stimuli and
      that may guide the emergence of cognition and consciousness? Analyzing brain
      recordings in conscious and unconscious states, we followed initially the classic
      approach in physics when it comes to understanding collective behaviours of
      systems composed of a myriad of units: the assessment of the number of possible
      configurations (microstates) that the system can adopt, for which we use a global
      entropic measure associated with the number of connected brain regions. Having
      found maximal entropy in conscious states, we then inspected the microscopic
      nature of the configurations of connections using an adequate complexity measure
      and found higher complexity in states characterized not only by conscious
      awareness but also by subconscious cognitive processing, such as sleep stages.
      Our observations indicate that conscious awareness is associated with maximal
      global (macroscopic) entropy and with the short time scale (microscopic)
      complexity of the configurations of connected brain networks in pathological
      unconscious states (seizures and coma), but the microscopic view captures the
      high complexity in physiological unconscious states (sleep) where there is
      information processing. As such, our results support the global nature of
      conscious awareness, as advocated by several theories of cognition. We thus hope
      that our studies represent preliminary steps to reveal aspects of the structure
      of cognition that leads to conscious awareness.

PMID- 29347349
TI  - Importance sampling with imperfect cloning for the computation of generalized
      Lyapunov exponents.
AB  - We revisit the numerical calculation of generalized Lyapunov exponents, L(q), in
      deterministic dynamical systems. The standard method consists of adding noise to
      the dynamics in order to use importance sampling algorithms. Then L(q) is
      obtained by taking the limit noise-amplitude -> 0 after the calculation. We focus
      on a particular method that involves periodic cloning and pruning of a set of
      trajectories. However, instead of considering a noisy dynamics, we implement an
      imperfect (noisy) cloning. This alternative method is compared with the standard
      one and, when possible, with analytical results. As a workbench we use the
      asymmetric tent map, the standard map, and a system of coupled symplectic maps.
      The general conclusion of this study is that the imperfect-cloning method
      performs as well as the standard one, with the advantage of preserving the
      deterministic dynamics.

PMID- 29347350
TI  - Birth of a subaqueous barchan dune.
AB  - Barchan dunes are crescentic shape dunes with horns pointing downstream. The
      present paper reports the formation of subaqueous barchan dunes from initially
      conical heaps in a rectangular channel. Because the most unique feature of a
      barchan dune is its horns, we associate the time scale for the appearance of
      horns to the formation of a barchan dune. A granular heap initially conical was
      placed on the bottom wall of a closed conduit and it was entrained by a water
      flow in turbulent regime. After a certain time, horns appear and grow, until an
      equilibrium length is reached. Our results show the existence of the time scales
      0.5t_{c} and 2.5t_{c} for the appearance and equilibrium of horns, respectively,
      where t_{c} is a characteristic time that scales with the grains diameter,
      gravity acceleration, densities of the fluid and grains, and shear and threshold
      velocities.

PMID- 29347351
TI  - Kinetics of doublet formation in bicomponent magnetic suspensions: The role of
      the magnetic permeability anisotropy.
AB  - Micron-sized particles (microbeads) dispersed in a suspension of magnetic
      nanoparticles, i.e., ferrofluids, can be assembled into different types of
      structures upon application of an external magnetic field. This paper is devoted
      to theoretical modeling of a relative motion of a pair of microbeads (either soft
      ferromagnetic or diamagnetic) in the ferrofluid under the action of applied
      uniform magnetic field which induces magnetic moments in the microbeads making
      them attracting to each other. The model is based on a point-dipole approximation
      for the magnetic interactions between microbeads mediated by the ferrofluid;
      however, the ferrofluid is considered to possess an anisotropic magnetic
      permeability thanks to field-induced structuring of its nanoparticles. The model
      is tested against experimental results and shows generally better agreement with
      experiments than the model considering isotropic magnetic permeability of
      ferrofluids. The results could be useful for understanding kinetics of
      aggregation of microbeads suspended in a ferrofluid. From a broader perspective,
      the present study is believed to contribute to a general understanding of
      particle behaviors in anisotropic media.

PMID- 29347352
TI  - Simple scaling laws for the evaporation of droplets pinned on pillars: Transfer
      rate- and diffusion-limited regimes.
AB  - The evaporation of droplets can give rise to a wide range of interesting
      phenomena in which the dynamics of the evaporation are crucial. In this work, we
      find simple scaling laws for the evaporation dynamics of axisymmetric droplets
      pinned on millimeter-sized pillars. Different laws are found depending on whether
      evaporation is limited by the diffusion of vapor molecules or by the transfer
      rate across the liquid-vapor interface. For the diffusion-limited regime, we find
      that a mass-loss rate equal to 3/7 of that of a free-standing evaporating droplet
      brings a good balance between simplicity and physical correctness. We also find a
      scaling law for the evaporation of multicomponent solutions. The scaling laws
      found are validated against experiments of the evaporation of droplets of (1)
      water, (2) blood plasma, and (3) a mixture of water and polyethylene glycol,
      pinned on acrylic pillars of different diameters. These results shed light on the
      macroscopic dynamics of evaporation on pillars as a first step towards the
      understanding of other complex phenomena that may be taking place during the
      evaporation process, such as particle transport and chemical reactions.

PMID- 29347353
TI  - Theory of nonstationary Hawkes processes.
AB  - We expand the theory of Hawkes processes to the nonstationary case, in which the
      mutually exciting point processes receive time-dependent inputs. We derive an
      analytical expression for the time-dependent correlations, which can be applied
      to networks with arbitrary connectivity, and inputs with arbitrary statistics.
      The expression shows how the network correlations are determined by the interplay
      between the network topology, the transfer functions relating units within the
      network, and the pattern and statistics of the external inputs. We illustrate the
      correlation structure using several examples in which neural network dynamics are
      modeled as a Hawkes process. In particular, we focus on the interplay between
      internally and externally generated oscillations and their signatures in the
      spike and rate correlation functions.

PMID- 29347354
TI  - Coarsening and pattern formation during true morphological phase separation in
      unstable thin films under gravity.
AB  - We address in detail the problem of true morphological phase separation (MPS) in
      three-dimensional or (2+1)-dimensional unstable thin liquid films (>100nm) under
      the influence of gravity. The free-energy functionals of these films are
      asymmetric and show two points of common tangency, which facilitates the
      formation of two equilibrium phases. Three distinct patterns formed by relative
      preponderance of these phases are clearly identified in "true MPS". Asymmetricity
      induces two different pathways of pattern formation, viz., defect and direct
      pathway for true MPS. The pattern formation and phase-ordering dynamics have been
      studied using statistical measures such as structure factor, correlation
      function, and growth laws. In the late stage of coarsening, the system reaches
      into a scaling regime for both pathways, and the characteristic domain size
      follows the Lifshitz-Slyozov growth law [L(t)~t^{1/3}]. However, for the defect
      pathway, there is a crossover of domain growth behavior from L(t)~t^{1/4}
      >t^{1/3} in the dynamical scaling regime. We also underline the analogies and
      differences behind the mechanisms of MPS and true MPS in thin liquid films and
      generic spinodal phase separation in binary mixtures.

PMID- 29347355
TI  - Inverse Ising problem in continuous time: A latent variable approach.
AB  - We consider the inverse Ising problem: the inference of network couplings from
      observed spin trajectories for a model with continuous time Glauber dynamics. By
      introducing two sets of auxiliary latent random variables we render the
      likelihood into a form which allows for simple iterative inference algorithms
      with analytical updates. The variables are (1) Poisson variables to linearize an
      exponential term which is typical for point process likelihoods and (2) Polya
      Gamma variables, which make the likelihood quadratic in the coupling parameters.
      Using the augmented likelihood, we derive an expectation-maximization (EM)
      algorithm to obtain the maximum likelihood estimate of network parameters. Using
      a third set of latent variables we extend the EM algorithm to sparse couplings
      via L1 regularization. Finally, we develop an efficient approximate Bayesian
      inference algorithm using a variational approach. We demonstrate the performance
      of our algorithms on data simulated from an Ising model. For data which are
      simulated from a more biologically plausible network with spiking neurons, we
      show that the Ising model captures well the low order statistics of the data and
      how the Ising couplings are related to the underlying synaptic structure of the
      simulated network.

PMID- 29347356
TI  - First- and second-order quantum phase transitions of a q-state Potts model in
      fractal lattices.
AB  - Quantum phase transitions of a q-state Potts model in fractal lattices are
      studied using a continuous-time quantum Monte Carlo simulation technique. For
      small values of q, the transition is found to be second order and critical
      exponents of the quantum critical point are calculated. The dynamic critical
      exponent z is found to be greater than one for all fractals studied, which is in
      contrast to integer-dimensional regular lattices. When q is greater than a
      certain value q_{c}, the phase transition becomes first order, where q_{c}
      depends on the lattice. Further analysis shows that the characteristics of phase
      transitions are more sensitive to the average number of nearest neighbors than
      the Hausdorff dimension or the order of ramification.

PMID- 29347357
TI  - Coupled Lorenz oscillators near the Hopf boundary: Multistability, intermingled
      basins, and quasiriddling.
AB  - We investigate the dynamics of coupled identical chaotic Lorenz oscillators just
      above the subcritical Hopf bifurcation. In the absence of coupling, the motion is
      on a strange chaotic attractor and the fixed points of the system are all
      unstable. With the coupling, the unstable fixed points are converted into chaotic
      attractors, and the system can exhibit a multiplicity of coexisting attractors.
      Depending on the strength of the coupling, the motion of the individual
      oscillators can be synchronized (both in and out of phase) or desynchronized and
      in addition there can be mixed phases. We find that the basins have a complex
      structure: the state that is asymptotically reached shows extreme sensitivity to
      initial conditions. The basins of attraction of these different states are
      characterized using a variety of measures and depending on the strength of the
      coupling, they are intermingled or quasiriddled.

PMID- 29347358
TI  - Divergence of activity expansions: Is it actually a problem?
AB  - For realistic interaction models, which include both molecular attraction and
      repulsion (e.g., Lennard-Jones, modified Lennard-Jones, Morse, and square-well
      potentials), the asymptotic behavior of the virial expansions for pressure and
      density in powers of activity has been studied taking power terms of high orders
      into account on the basis of the known finite-order irreducible integrals as well
      as the recent approximations of infinite irreducible series. Even in the
      divergence region (at subcritical temperatures), this behavior stays
      thermodynamically adequate (in contrast to the behavior of the virial equation of
      state with the same set of irreducible integrals) and corresponds to the
      beginning of the first-order phase transition: the divergence yields the jump
      (discontinuity) in density at constant pressure and chemical potential. In
      general, it provides a statistical explanation of the condensation phenomenon,
      but for liquid or solid states, the physically proper description (which can turn
      the infinite discontinuity into a finite jump of density) still needs further
      study of high-order cluster integrals and, especially, their real dependence on
      the system volume (density).

PMID- 29347359
TI  - Self-organized emergence of multilayer structure and chimera states in dynamical
      networks with adaptive couplings.
AB  - We report the phenomenon of self-organized emergence of hierarchical multilayered
      structures and chimera states in dynamical networks with adaptive couplings. This
      process is characterized by a sequential formation of subnetworks (layers) of
      densely coupled elements, the size of which is ordered in a hierarchical way, and
      which are weakly coupled between each other. We show that the hierarchical
      structure causes the decoupling of the subnetworks. Each layer can exhibit either
      a two-cluster state, a periodic traveling wave, or an incoherent state, and these
      states can coexist on different scales of subnetwork sizes.

PMID- 29347360
TI  - Incorporation of velocity-dependent restitution coefficient and particle surface
      friction into kinetic theory for modeling granular flow cooling.
AB  - Kinetic theory (KT) has been successfully used to model rapid granular flows in
      which particle interactions are frictionless and near elastic. However, it fails
      when particle interactions become frictional and inelastic. For example, the KT
      is not able to accurately predict the free cooling process of a vibrated granular
      medium that consists of inelastic frictional particles under microgravity. The
      main reason that the classical KT fails to model these flows is due to its
      inability to account for the particle surface friction and its inelastic
      behavior, which are the two most important factors that need be considered in
      modeling collisional granular flows. In this study, we have modified the KT model
      that is able to incorporate these two factors. The inelasticity of a particle is
      considered by establishing a velocity-dependent expression for the restitution
      coefficient based on many experimental studies found in the literature, and the
      particle friction effect is included by using a tangential restitution
      coefficient that is related to the particle friction coefficient. Theoretical
      predictions of the free cooling process by the classical KT and the improved KT
      are compared with the experimental results from a study conducted on an airplane
      undergoing parabolic flights without the influence of gravity [Y. Grasselli, G.
      Bossis, and G. Goutallier, Europhys. Lett. 86, 60007 (2009)10.1209/0295
      5075/86/60007]. Our results show that both the velocity-dependent restitution
      coefficient and the particle surface friction are important in predicting the
      free cooling process of granular flows; the modified KT model that integrates
      these two factors is able to improve the simulation results and leads to better
      agreement with the experimental results.

PMID- 29347361
TI  - Folding time dependence of the motions of a molecular motor in an amorphous
      medium.
AB  - We investigate the dependence of the displacements of a molecular motor embedded
      inside a glassy material on its folding characteristic time tau_{f}. We observe
      two different time regimes. For slow foldings (regime I) the diffusion evolves
      very slowly with tau_{f}, while for rapid foldings (regime II) the diffusion
      increases strongly with tau_{f}(D~tau_{f}^{-2}), suggesting two different
      physical mechanisms. We find that in regime I the motor's displacement during the
      folding process is counteracted by a reverse displacement during the unfolding,
      while in regime II this counteraction is much weaker. We notice that regime I
      behavior is reminiscent of the scallop theorem that holds for larger motors in a
      continuous medium. We find that the difference in the efficiency of the motor's
      motion explains most of the observed difference between the two regimes. For fast
      foldings the motor trajectories differ significantly from the opposite
      trajectories induced by the following unfolding process, resulting in a more
      efficient global motion than for slow foldings. This result agrees with the
      fluctuation theorems expectation for time reversal mechanisms. In agreement with
      the fluctuation theorems we find that the motors are unexpectedly more efficient
      when they are generating more entropy, a result that can be used to increase
      dramatically the motor's motion.

PMID- 29347362
TI  - Phase transitions in a system of long rods on two-dimensional lattices by means
      of information theory.
AB  - The orientational phase transitions that occur in the deposition of longitudinal
      polymers of length k (in terms of lattice units) are characterized by information
      theory techniques. We calculate the absolute value of an order parameter delta,
      which weights the relative orientations of the deposited rods, which varies
      between 0.0 (random orientation) and 1.0 (fully oriented in either of the two
      equivalent directions in an L*L square lattice). A Monte Carlo (MC) algorithm is
      implemented to induce a dynamics allowing for accommodation of the rods for any
      given density or coverage theta (ratio of the occupied sites over all the sites
      in the lattice). The files storing delta(t) (with time t measured in MC steps)
      are then treated by data recognizer wlzip based on data compressor techniques
      yielding the information content measured by a parameter eta(theta). This allows
      us to recognize two maxima separated by a well-defined minimum for eta(theta)
      provided k>=7. The first maximum is associated with an isotropic-nematic (I-N)
      phase transition occurring at intermediate density, while the second maximum is
      associated with some kind of nematic-isotropic transition at high coverage. In
      the cases of k<7, the curves for eta(theta) are almost constant, presenting a
      very broad maximum which can hardly be associated with a phase transition. The
      study varies L and k, allowing for a basic scaling of the found critical
      densities towards the thermodynamic limit. These calculations confirm the
      tendency obtained by different methods in the case of the intermediate-density I
      N phase transition, while this tendency is established here in the case of the
      high-density phase transition.

PMID- 29347363
TI  - Control of viscous fingering by nanoparticles.
AB  - A substantial viscosity increase by the addition of a low dose of nanoparticles
      to the base fluids can well influence the dynamics of viscous fingering. There is
      a lack of detailed theoretical studies that address the effect of the presence of
      nanoparticles on unstable miscible displacements. In this study, the impact of
      nonreactive nanoparticle presence on the stability and subsequent mixing of an
      originally unstable binary system is examined using linear stability analysis
      (LSA) and pseudospectral-based direct numerical simulations (DNS). We have
      parametrized the role of both nondepositing and depositing nanoparticles on the
      stability of miscible displacements using the developed static and dynamic
      parametric analyses. Our results show that nanoparticles have the potential to
      weaken the instabilities of an originally unstable system. Our LSA and DNS
      results also reveal that nondepositing nanoparticles can be used to fully
      stabilize an originally unstable front while depositing particles may act as
      temporary stabilizers whose influence diminishes in the course of time. In
      addition, we explain the existing inconsistencies concerning the effect of the
      nanoparticle diffusion coefficient on the dynamics of the system. This study
      provides a basis for further research on the application of nanoparticles for
      control of viscosity-driven instabilities.

PMID- 29347364
TI  - Distribution of shortest cycle lengths in random networks.
AB  - We present analytical results for the distribution of shortest cycle lengths
      (DSCL) in random networks. The approach is based on the relation between the DSCL
      and the distribution of shortest path lengths (DSPL). We apply this approach to
      configuration model networks, for which analytical results for the DSPL were
      obtained before. We first calculate the fraction of nodes in the network which
      reside on at least one cycle. Conditioning on being on a cycle, we provide the
      DSCL over ensembles of configuration model networks with degree distributions
      which follow a Poisson distribution (Erdos-Renyi network), degenerate
      distribution (random regular graph), and a power-law distribution (scale-free
      network). The mean and variance of the DSCL are calculated. The analytical
      results are found to be in very good agreement with the results of computer
      simulations.

PMID- 29347365
TI  - Solution x-ray scattering and structure formation in protein dynamics.
AB  - We propose a computationally effective approach that builds on Landau mean-field
      theory in combination with modern nonequilibrium statistical mechanics to model
      and interpret protein dynamics and structure formation in small- to wide-angle x
      ray scattering (S/WAXS) experiments. We develop the methodology by analyzing
      experimental data in the case of Engrailed homeodomain protein as an example. We
      demonstrate how to interpret S/WAXS data qualitatively with a good precision and
      over an extended temperature range. We explain experimental observations in terms
      of protein phase structure, and we make predictions for future experiments and
      for how to analyze data at different ambient temperature values. We conclude that
      the approach we propose has the potential to become a highly accurate,
      computationally effective, and predictive tool for analyzing S/WAXS data. For
      this, we compare our results with those obtained previously in an all-atom
      molecular dynamics simulation.

PMID- 29347366
TI  - Switching synchronization in one-dimensional memristive networks: An exact
      solution.
AB  - We study a switching synchronization phenomenon taking place in one-dimensional
      memristive networks when the memristors switch from the high- to low-resistance
      state. It is assumed that the distributions of threshold voltages and switching
      rates of memristors are arbitrary. Using the Laplace transform, a set of
      nonlinear equations describing the memristors dynamics is solved exactly, without
      any approximations. The time dependencies of memristances are found, and it is
      shown that the voltage falls across memristors are proportional to their
      threshold voltages. A compact expression for the network switching time is
      derived.

PMID- 29347368
TI  - Three-scale analysis of the permeability of a natural shale.
AB  - The macroscopic permeability of a natural shale is determined by using structural
      measurements on three different scales. Transmission electron microscopy yields
      two-dimensional (2D) images with pixels smaller than 1 nm; these images are used
      to reconstruct 3D nanostructures. Three-dimensional focused ion beam-scanning
      electron microscopy (5.95- to 8.48-nm voxel size) provides 3D mesoscale pores of
      limited relative volume (1.71-5.9%). Micro-computed tomography (700-nm voxel
      size) provides information on the mineralogy of the shale, including the pores on
      this scale which do not percolate; synthetic 3D media are derived on the
      macroscopic scale by a training image technique. Permeability of the nanoscale,
      of the mesoscale structures and of their superposition is determined by solving
      the Stokes equation and this enables us to estimate the permeabilities of the 700
      nm voxels located within the clay matrix. Finally, the Darcy equation is solved
      on synthetic 3D macroscale media to obtain the macroscopic permeability which is
      found in good agreement with experimental results obtained on the centimetric
      scale.

PMID- 29347367
TI  - Elastic and viscous properties of the nematic dimer CB7CB.
AB  - We present a comprehensive set of measurements of optical, dielectric,
      diamagnetic, elastic, and viscous properties in the nematic (N) phase formed by a
      liquid crystalline dimer. The studied dimer, 1,7-bis-4-(4'-cyanobiphenyl) heptane
      (CB7CB), is composed of two rigid rodlike cyanobiphenyl segments connected by a
      flexible aliphatic link with seven methyl groups. CB7CB and other nematic dimers
      are of interest due to their tendency to adopt bent configurations and to form
      two states possessing a modulated nematic director structure, namely, the twist
      bend nematic, N_{TB}, and the oblique helicoidal cholesteric, Ch_{OH}, which
      occurs when the achiral dimer is doped with a chiral additive and exposed to an
      external electric or magnetic field. We characterize the material parameters as
      functions of temperature in the entire temperature range of the N phase,
      including the pretransitional regions near the N-N_{TB} and N-to-isotropic (I)
      transitions. The splay constant K_{11} is determined by two direct and
      independent techniques, namely, detection of the Frederiks transition and
      measurement of director fluctuation amplitudes by dynamic light scattering (DLS).
      The bend K_{33} and twist K_{22} constants are measured by DLS. K_{33}, being the
      smallest of the three constants, shows a strong nonmonotonous temperature
      dependence with a negative slope in both N-I and N-N_{TB} pretransitional
      regions. The measured ratio K_{11}/K_{22} is larger than 2 in the entire nematic
      temperature range. The orientational viscosities associated with splay, twist,
      and bend fluctuations in the N phase are comparable to those of nematics formed
      by rodlike molecules. All three show strong temperature dependence, increasing
      sharply near the N-N_{TB} transition.

PMID- 29347369
TI  - Relaxation-type nonlocal inertial-number rheology for dry granular flows.
AB  - We propose a constitutive model to describe the nonlocality, hysteresis, and
      several flow features of dry granular materials. Taking the well-known inertial
      number I as a measure of sheared-induced local fluidization, we derive a
      relaxation model for I according to the evolution of microstructure during
      avalanche and dissipation processes. The model yields a nonmonotonic flow law for
      a homogeneous flow, accounting for hysteretic solid-fluid transition and
      intermittency in quasistatic flows. For an inhomogeneous flow, the model predicts
      a generalized Bagnold shear stress revealing the interplay of two microscopic
      nonlocal mechanisms: collisions among correlated structures and the diffusion of
      fluidization within the structures. In describing a uniform flow down an incline,
      the model reproduces the hysteretic starting and stopping heights and the
      Pouliquen flow rule for mean velocity. Moreover, a dimensionless parameter
      reflecting the nonlocal effect on the flow is discovered, which controls the
      transition between Bagnold and creeping flow dynamics.

PMID- 29347370
TI  - Crucial events, randomness, and multifractality in heartbeats.
AB  - We study the connection between multifractality and crucial events.
      Multifractality is frequently used as a measure of physiological variability,
      where crucial events are known to play a fundamental role in the transport of
      information between complex networks. To establish the connection of interest we
      focus on the special case of heartbeat time series and on the search for a
      diagnostic prescription to distinguish healthy from pathologic subjects. Over the
      past 20 years two apparently different diagnostic techniques have been
      established: the first is based on the observation that the multifractal spectrum
      of healthy patients is broader than the multifractal spectrum of pathologic
      subjects; the second is based on the observation that heartbeat dynamics are a
      superposition of crucial and uncorrelated Poisson-like events, with pathologic
      patients hosting uncorrelated Poisson-like events with larger probability than
      the healthy patients. In this paper, we prove that increasing the percentage of
      uncorrelated Poisson-like events hosted by heartbeats has the effect of making
      their multifractal spectrum narrower, thereby establishing that the two different
      diagnostic techniques are compatible with one another and, at the same time,
      establishing a dynamic interpretation of multifractal processes that had been
      previously overlooked.

PMID- 29347371
TI  - Boundary effects in a quasi-two-dimensional driven granular fluid.
AB  - The effect of a confining boundary on the spatial variations in granular
      temperature of a driven quasi-two-dimensional layer of particles is investigated
      experimentally. The radial drop in the relative granular temperature DeltaT/T
      exhibits a maximum at intermediate particle numbers which coincides with a
      crossover from kinetic to collisional transport of energy. It is also found that
      at low particle numbers, the distributions of radial velocities are increasingly
      asymmetric as one approaches the boundary. The radial and tangential granular
      temperatures split, and in the tails of the radial velocity distribution there is
      a higher population of fast moving particles traveling away rather than towards
      the boundary.

PMID- 29347372
TI  - Lattice Boltzmann heat transfer model for permeable voxels.
AB  - We develop a gray-scale lattice Boltzmann (LB) model to study fluid flow combined
      with heat transfer for flow through porous media where voxels may be partially
      solid (or void). Heat transfer in rocks may lead to deformation, which in turn
      can modulate the fluid flow and so has significant contribution to rock
      permeability. The LB temperature field is compared to a finite difference
      solution of the continuum partial differential equations for fluid flow in a
      channel. Excellent quantitative agreement is found for both Poiseuille channel
      flow and Brinkman flow. The LB model is then applied to sample porous media such
      as packed beds and also more realistic sandstone rock sample, and both the
      convective and diffusive regimes are recovered when varying the thermal
      diffusivity. It is found that while the rock permeability can be comparatively
      small (order milli-Darcy), the temperature field can show significant variation
      depending on the thermal convection of the fluid. This LB method has significant
      advantages over other numerical methods such as finite and boundary element
      methods in dealing with coupled fluid flow and heat transfer in rocks which have
      irregular and nonsmooth pore spaces.

PMID- 29347373
TI  - Quantum chaos for nonstandard symmetry classes in the Feingold-Peres model of
      coupled tops.
AB  - We consider two coupled quantum tops with angular momentum vectors L and M. The
      coupling Hamiltonian defines the Feingold-Peres model, which is a known paradigm
      of quantum chaos. We show that this model has a nonstandard symmetry with respect
      to the Altland-Zirnbauer tenfold symmetry classification of quantum systems,
      which extends the well-known threefold way of Wigner and Dyson (referred to as
      "standard" symmetry classes here). We identify the nonstandard symmetry classes
      BDI_{0} (chiral orthogonal class with no zero modes), BDI_{1} (chiral orthogonal
      class with one zero mode), and CI (antichiral orthogonal class) as well as the
      standard symmetry class AI (orthogonal class). We numerically analyze the
      specific spectral quantum signatures of chaos related to the nonstandard
      symmetries. In the microscopic density of states and in the distribution of the
      lowest positive energy eigenvalue, we show that the Feingold-Peres model follows
      the predictions of the Gaussian ensembles of random-matrix theory in the
      appropriate symmetry class if the corresponding classical dynamics is chaotic. In
      a crossover to mixed and near-integrable classical dynamics, we show that these
      signatures disappear or strongly change.

PMID- 29347374
TI  - Relative velocities in bidisperse turbulent suspensions.
AB  - We investigate the distribution of relative velocities between small heavy
      particles of different sizes in turbulence by analyzing a statistical model for
      bidisperse turbulent suspensions, containing particles with two different Stokes
      numbers. This number, St, is a measure of particle inertia which in turn depends
      on particle size. When the Stokes numbers are similar, the distribution exhibits
      power-law tails, just as in the case of equal St. The power-law exponent is a
      nonanalytic function of the mean Stokes number St[over -], so that the exponent
      cannot be calculated in perturbation theory around the advective limit. When the
      Stokes-number difference is larger, the power law disappears, but the tails of
      the distribution still dominate the relative-velocity moments, if St[over -] is
      large enough.

PMID- 29347375
TI  - Probing the anomalous dynamical phase in long-range quantum spin chains through
      Fisher-zero lines.
AB  - Using the framework of infinite matrix product states, the existence of an
      anomalous dynamical phase for the transverse-field Ising chain with sufficiently
      long-range interactions was first reported in J. C. Halimeh and V. Zauner-Stauber
      [Phys. Rev. B 96, 134427 (2017)10.1103/PhysRevB.96.134427], where it was shown
      that anomalous cusps arise in the Loschmidt-echo return rate for sufficiently
      small quenches within the ferromagnetic phase. In this work we further probe the
      nature of the anomalous phase through calculating the corresponding Fisher-zero
      lines in the complex time plane. We find that these Fisher-zero lines exhibit a
      qualitative difference in their behavior, where, unlike in the case of the
      regular phase, some of them terminate before intersecting the imaginary axis,
      indicating the existence of smooth peaks in the return rate preceding the cusps.
      Additionally, we discuss in detail the infinite matrix product state time
      evolution method used to calculate Fisher zeros and the Loschmidt-echo return
      rate using the matrix product state transfer matrix. Our work sheds further light
      on the nature of the anomalous phase in the long-range transverse-field Ising
      chain, while the numerical treatment presented can be applied to more general
      quantum spin chains.

PMID- 29347376
TI  - Numerical solution of the general coupled nonlinear Schrodinger equations on
      unbounded domains.
AB  - The numerical solution of the general coupled nonlinear Schrodinger equations on
      unbounded domains is considered by applying the artificial boundary method in
      this paper. In order to design the local absorbing boundary conditions for the
      coupled nonlinear Schrodinger equations, we generalize the unified approach
      previously proposed [J. Zhang et al., Phys. Rev. E 78, 026709 (2008)PLEEE81539
      375510.1103/PhysRevE.78.026709]. Based on the methodology underlying the unified
      approach, the original problem is split into two parts, linear and nonlinear
      terms, and we then achieve a one-way operator to approximate the linear term to
      make the wave out-going, and finally we combine the one-way operator with the
      nonlinear term to derive the local absorbing boundary conditions. Then we reduce
      the original problem into an initial boundary value problem on the bounded
      domain, which can be solved by the finite difference method. The stability of the
      reduced problem is also analyzed by introducing some auxiliary variables. Ample
      numerical examples are presented to verify the accuracy and effectiveness of our
      proposed method.

PMID- 29347377
TI  - Edge instability in incompressible planar active fluids.
AB  - Interfacial instability is highly relevant to many important biological
      processes. A key example arises in wound healing experiments, which observe that
      an epithelial layer with an initially straight edge does not heal uniformly. We
      consider the phenomenon in the context of active fluids. Improving upon the
      approximation used by Zimmermann, Basan, and Levine [Eur. Phys. J.: Spec. Top.
      223, 1259 (2014)1951-635510.1140/epjst/e2014-02189-7], we perform a linear
      stability analysis on a two-dimensional incompressible hydrodynamic model of an
      active fluid with an open interface. We categorize the stability of the model and
      find that for experimentally relevant parameters, fingering instability is always
      absent in this minimal model. Our results point to the crucial role of density
      variation in the fingering instability in tissue regeneration.

PMID- 29347378
TI  - Interfacial mixing in high-energy-density matter with a multiphysics kinetic
      model.
AB  - We have extended a recently developed multispecies, multitemperature Bhatnagar
      Gross-Krook model [Haack et al., J. Stat. Phys. 168, 822 (2017)JSTPBS0022
      471510.1007/s10955-017-1824-9], to include multiphysics capabilities that enable
      modeling of a wider range of physical conditions. In terms of geometry, we have
      extended from the spatially homogeneous setting to one spatial dimension. In
      terms of the physics, we have included an atomic ionization model, accurate
      collision physics across coupling regimes, self-consistent electric fields, and
      degeneracy in the electronic screening. We apply the model to a warm dense matter
      scenario in which the ablator-fuel interface of an inertial confinement fusion
      target is heated, but for larger length and time scales and for much higher
      temperatures than can be simulated using molecular dynamics. Relative to
      molecular dynamics, the kinetic model greatly extends the temperature regime and
      the spatiotemporal scales over which we are able to model. In our numerical
      results we observe hydrogen from the ablator material jetting into the fuel
      during the early stages of the implosion and compare the relative size of various
      diffusion components (Fickean diffusion, electrodiffusion, and barodiffusion)
      that drive this process. We also examine kinetic effects, such as anisotropic
      distributions and velocity separation, in order to determine when this problem
      can be described with a hydrodynamic model.

PMID- 29347379
TI  - Neuronal network model of interictal and recurrent ictal activity.
AB  - We propose a neuronal network model which undergoes a saddle node on an invariant
      circle bifurcation as the mechanism of the transition from the interictal to the
      ictal (seizure) state. In the vicinity of this transition, the model captures
      important dynamical features of both interictal and ictal states. We study the
      nature of interictal spikes and early warnings of the transition predicted by
      this model. We further demonstrate that recurrent seizures emerge due to the
      interaction between two networks.

PMID- 29347380
TI  - Homoclinic snaking in the discrete Swift-Hohenberg equation.
AB  - We consider the discrete Swift-Hohenberg equation with cubic and quintic
      nonlinearity, obtained from discretizing the spatial derivatives of the Swift
      Hohenberg equation using central finite differences. We investigate the
      discretization effect on the bifurcation behavior, where we identify three
      regions of the coupling parameter, i.e., strong, weak, and intermediate coupling.
      Within the regions, the discrete Swift-Hohenberg equation behaves either
      similarly or differently from the continuum limit. In the intermediate coupling
      region, multiple Maxwell points can occur for the periodic solutions and may
      cause irregular snaking and isolas. Numerical continuation is used to obtain and
      analyze localized and periodic solutions for each case. Theoretical analysis for
      the snaking and stability of the corresponding solutions is provided in the weak
      coupling region.

PMID- 29347381
TI  - Maximum entropy modeling of metabolic networks by constraining growth-rate
      moments predicts coexistence of phenotypes.
AB  - In this work maximum entropy distributions in the space of steady states of
      metabolic networks are considered upon constraining the first and second moments
      of the growth rate. Coexistence of fast and slow phenotypes, with bimodal flux
      distributions, emerges upon considering control on the average growth
      (optimization) and its fluctuations (heterogeneity). This is applied to the
      carbon catabolic core of Escherichia coli where it quantifies the metabolic
      activity of slow growing phenotypes and it provides a quantitative map with
      metabolic fluxes, opening the possibility to detect coexistence from flux data. A
      preliminary analysis on data for E. coli cultures in standard conditions shows
      degeneracy for the inferred parameters that extend in the coexistence region.

PMID- 29347382
TI  - Aging in mortal superdiffusive Levy walkers.
AB  - A growing body of literature examines the effects of superdiffusive subballistic
      movement premeasurement (aging or time lag) on observations arising from single
      particle tracking. A neglected aspect is the finite lifetime of these Levy
      walkers, be they proteins, cells, or larger structures. We examine the effects of
      aging on the motility of mortal walkers, and discuss the means by which permanent
      stopping of walkers may be categorized as arising from "natural" death or
      experimental artifacts such as low photostability or radiation damage. This is
      done by comparison of the walkers' mean squared displacement (MSD) with the front
      velocity of propagation of a group of walkers, which is found to be invariant
      under time lags. For any running time distribution of a mortal random walker, the
      MSD is tempered by the stopping rate theta. This provides a physical
      interpretation for truncated heavy-tailed diffusion processes and serves as a
      tool by which to better classify the underlying running time distributions of
      random walkers. Tempering of aged MSDs raises the issue of misinterpreting
      superdiffusive motion which appears Brownian or subdiffusive over certain time
      scales.

PMID- 29347383
TI  - Wavelet-based regularization of the Galerkin truncated three-dimensional
      incompressible Euler flows.
AB  - We present numerical simulations of the three-dimensional Galerkin truncated
      incompressible Euler equations that we integrate in time while regularizing the
      solution by applying a wavelet-based denoising. For this, at each time step, the
      vorticity field is decomposed into wavelet coefficients, which are split into
      strong and weak coefficients, before reconstructing them in physical space to
      obtain the corresponding coherent and incoherent vorticities. Both components are
      multiscale and orthogonal to each other. Then, by using the Biot-Savart kernel,
      one obtains the coherent and incoherent velocities. Advancing the coherent flow
      in time, while filtering out the noiselike incoherent flow, models turbulent
      dissipation and corresponds to an adaptive regularization. To track the flow
      evolution in both space and scale, a safety zone is added in wavelet coefficient
      space to the coherent wavelet coefficients. It is shown that the coherent flow
      indeed exhibits an intermittent nonlinear dynamics and a k^{-5/3} energy
      spectrum, where k is the wave number, characteristic of three-dimensional
      homogeneous isotropic turbulence. Finally, we compare the dynamical and
      statistical properties of Euler flows subjected to four kinds of regularizations:
      dissipative (Navier-Stokes), hyperdissipative (iterated Laplacian), dispersive
      (Euler-Voigt), and wavelet-based regularizations.

PMID- 29347384
TI  - Bifurcation analysis and phase diagram of a spin-string model with buckled
      states.
AB  - We analyze a one-dimensional spin-string model, in which string oscillators are
      linearly coupled to their two nearest neighbors and to Ising spins representing
      internal degrees of freedom. String-spin coupling induces a long-range
      ferromagnetic interaction among spins that competes with a spin-spin
      antiferromagnetic coupling. As a consequence, the complex phase diagram of the
      system exhibits different flat rippled and buckled states, with first or second
      order transition lines between states. This complexity translates to the two
      dimensional version of the model, whose numerical solution has been recently used
      to explain qualitatively the rippled to buckled transition observed in scanning
      tunneling microscopy experiments with suspended graphene sheets. Here we describe
      in detail the phase diagram of the simpler one-dimensional model and phase
      stability using bifurcation theory. This gives additional insight into the
      physical mechanisms underlying the different phases and the behavior observed in
      experiments.

PMID- 29347385
TI  - Organization and scaling in water supply networks.
AB  - Public water supply is one of the society's most vital resources and most costly
      infrastructures. Traditional concepts of these networks capture their engineering
      identity as isolated, deterministic hydraulic units, but overlook their physics
      identity as related entities in a probabilistic, geographic ensemble,
      characterized by size organization and property scaling. Although discoveries of
      allometric scaling in natural supply networks (organisms and rivers) raised the
      prospect for similar findings in anthropogenic supplies, so far such a finding
      has not been reported in public water or related civic resource supplies.
      Examining an empirical ensemble of large number and wide size range, we show that
      water supply networks possess self-organized size abundance and theory-explained
      allometric scaling in spatial, infrastructural, and resource- and emission-flow
      properties. These discoveries establish scaling physics for water supply networks
      and may lead to novel applications in resource- and jurisdiction-scale water
      governance.

PMID- 29347386
TI  - Finite plateau in spectral gap of polychromatic constrained random networks.
AB  - We consider critical behavior in the ensemble of polychromatic Erdos-Renyi
      networks and regular random graphs, where network vertices are painted in
      different colors. The links can be randomly removed and added to the network
      subject to the condition of the vertex degree conservation. In these constrained
      graphs we run the Metropolis procedure, which favors the connected unicolor
      triads of nodes. Changing the chemical potential, MU, of such triads, for some
      wide region of MU, we find the formation of a finite plateau in the number of
      intercolor links, which exactly matches the finite plateau in the network
      algebraic connectivity (the value of the first nonvanishing eigenvalue of the
      Laplacian matrix, lambda_{2}). We claim that at the plateau the spontaneously
      broken Z_{2} symmetry is restored by the mechanism of modes collectivization in
      clusters of different colors. The phenomena of a finite plateau formation holds
      also for polychromatic networks with M>=2 colors. The behavior of polychromatic
      networks is analyzed via the spectral properties of their adjacency and Laplacian
      matrices.

PMID- 29347387
TI  - Anomalous interfacial temperature profile induced by phonon localization.
AB  - Through the integration of the power spectral density, we obtain temperature
      profiles of both multisegment harmonic and anharmonic systems, showing the
      presence of an anomalous negative temperature gradient inside the interfacial
      segment. Via investigating patterns of the power spectral density, we found that
      the counterintuitive phenomenon comes from the presence of interfacial localized
      phonon modes. Two out-band localized modes of the harmonic model, which make no
      contributions to local temperature due to the absence of phonon interactions,
      result in the concave temperature profile and overcooling effect. For the
      anharmonic model, thanks to the phonon-phonon interactions, the localized modes
      are excited and make considerable contributions to interfacial temperature, which
      is clearly shown by examining the temperature accumulation function. When
      anharmonicity is considerably large, the negative temperature gradient is absent
      since the localized phonon modes are fully mixed. The presence of localized modes
      are evidently demonstrated by the inverse participation ratio and normal mode
      analysis for the isolated harmonic model. The localized modes make contribution
      to interfacial temperature profiles of the harmonic system when they are excited
      in initial conditions of simulations.

PMID- 29347388
TI  - Finite volume method for self-consistent field theory of polymers: Material
      conservation and application.
AB  - For the purpose of checking material conservation of various numerical algorithms
      used in the self-consistent-field theory (SCFT) of polymeric systems, we develop
      an algebraic method using matrix and bra-ket notation, which traces the
      Hermiticity of the product of the volume and evolution matrices. Algebraic tests
      for material conservation reveal that the popular pseudospectral method in the
      Cartesian grid conserves material perfectly, while the finite-volume method (FVM)
      is the proper tool when real-space SCFT with the Crank-Nicolson method is adopted
      in orthogonal coordinate systems. We also find that alternating direction
      implicit methods combined with the FVM exhibit small mass errors in the SCFT
      calculation. By introducing fractional cells in the FVM formulation, accurate
      SCFT calculations are performed for systems with irregular geometries and the
      results are consistent with previous experimental and theoretical works.

PMID- 29347389
TI  - Integral fluctuation theorems for stochastic resetting systems.
AB  - We study the stochastic thermodynamics of resetting systems. Violation of
      microreversibility means that the well-known derivations of fluctuations theorems
      break down for dynamics with resetting. Despite that we show that stochastic
      resetting systems satisfy two integral fluctuation theorems. The first is the
      Hatano-Sasa relation describing the transition between two steady states. The
      second integral fluctuation theorem involves a functional that includes both
      dynamical and thermodynamic contributions. We find that the second law-like
      inequality found by Fuchs et al. for resetting systems [Europhys. Lett. 113,
      60009 (2016)EULEEJ0295-507510.1209/0295-5075/113/60009] can be recovered from
      this integral fluctuation theorem with the help of Jensen's inequality.

PMID- 29347390
TI  - Coalescing colony model: Mean-field, scaling, and geometry.
AB  - We analyze the coalescing model where a 'primary' colony grows and randomly emits
      secondary colonies that spread and eventually coalesce with it. This model
      describes population proliferation in theoretical ecology, tumor growth, and is
      also of great interest for modeling urban sprawl. Assuming the primary colony to
      be always circular of radius r(t) and the emission rate proportional to
      r(t)^{theta}, where theta>0, we derive the mean-field equations governing the
      dynamics of the primary colony, calculate the scaling exponents versus theta, and
      compare our results with numerical simulations. We then critically test the
      validity of the circular approximation for the colony shape and show that it is
      sound for a constant emission rate (theta=0). However, when the emission rate is
      proportional to the perimeter, the circular approximation breaks down and the
      roughness of the primary colony cannot be discarded, thus modifying the scaling
      exponents.

PMID- 29347391
TI  - Search efficiency of biased migration towards stationary or moving targets in
      heterogeneously structured environments.
AB  - Efficient search acts as a strong selective force in biological systems ranging
      from cellular populations to predator-prey systems. The search processes commonly
      involve finding a stationary or mobile target within a heterogeneously structured
      environment where obstacles limit migration. An open generic question is whether
      random or directionally biased motions or a combination of both provide an
      optimal search efficiency and how that depends on the motility and density of
      targets and obstacles. To address this question, we develop a simple model that
      involves a random walker searching for its targets in a heterogeneous medium of
      bond percolation square lattice and used mean first passage time (<T>) as an
      indication of average search time. Our analysis reveals a dual effect of
      directional bias on the minimum value of <T>. For a homogeneous medium,
      directionality always decreases <T> and a pure directional migration (a ballistic
      motion) serves as the optimized strategy, while for a heterogeneous environment,
      we find that the optimized strategy involves a combination of directed and random
      migrations. The relative contribution of these modes is determined by the density
      of obstacles and motility of targets. Existence of randomness and motility of
      targets add to the efficiency of search. Our study reveals generic and simple
      rules that govern search efficiency. Our findings might find application in a
      number of areas including immunology, cell biology, ecology, and robotics.

PMID- 29347392
TI  - Two-dimensional dynamics of a trapped active Brownian particle in a shear flow.
AB  - We model the two-dimensional dynamics of a pointlike artificial microswimmer
      diffusing in a harmonic trap subject to the shear flow of a highly viscous
      medium. The particle is driven simultaneously by the linear restoring force of
      the trap, the drag force exerted by the flow, and the torque due to the shear
      gradient. For a Couette flow, elliptical orbits in the noiseless regime, and the
      correlation functions between the particle's displacements parallel and
      orthogonal to the flow are computed analytically. The effects of thermal
      fluctuations (translational) and self-propulsion fluctuations (angular) are
      treated separately. Finally, we discuss how to extend our approach to the
      diffusion of a microswimmer in a Poiseuille flow. These results provide an
      accurate reference solution to investigate, both numerically and experimentally,
      hydrodynamics corrections to the diffusion of active matter in confined
      geometries.

PMID- 29347393
TI  - Ultrasonic waves in classical gases.
AB  - The velocity and absorption coefficient for the plane sound waves in a classical
      gas are obtained by solving the Boltzmann kinetic equation, which describes the
      reaction of the single-particle distribution function to a periodic external
      field. Within the linear response theory, the nonperturbative dispersion equation
      valid for all sound frequencies is derived and solved numerically. The results
      are in agreement with the approximate analytical solutions found for both the
      frequent- and rare-collision regimes. These results are also in qualitative
      agreement with the experimental data for ultrasonic waves in dilute gases.

PMID- 29347394
TI  - Linking biological and physical aging: Dynamical scaling of multicellular
      regeneration.
AB  - The fight against biological aging (bio-aging) is long-standing, with the focus
      of intense research aimed at maintaining high rates of tissue regeneration to
      promote health and longevity. Nevertheless, there are overwhelming complexities
      associated with the quantitative analysis of aging. In this study, we sought to
      quantify bio-aging based on physical aging, by mapping instances of multicellular
      regeneration to the relaxation of physical systems. An experiment of delayed
      wound healing assays was devised to obtain delay-dependent healing data. The
      experiment confirmed the slowdown of healing events, which fitted dynamical
      scaling just as relaxation events do in physical aging. The scaling exponent,
      which describes the aging rate in physics, is here similarly proposed as an
      indicator of the deterioration rate of tissue-regenerative power. Parallel
      equation-based and cell-based simulations also revealed that asymmetric cell
      cycle-regulatory mechanisms under strong growth-inhibitory conditions
      predominantly control the critical slowdown of healing analogous to physical
      criticality. By establishing a direct link between physical aging and biological
      aging, we are able to estimate the aging rate of tissues and to achieve an
      integrated understanding of bio-aging mechanism which may improve the modulation
      of regeneration for clinical use.

PMID- 29347395
TI  - Scarcity of crossing dependencies: A direct outcome of a specific constraint?
AB  - The structure of a sentence can be represented as a network where vertices are
      words and edges indicate syntactic dependencies. Interestingly, crossing
      syntactic dependencies have been observed to be infrequent in human languages.
      This leads to the question of whether the scarcity of crossings in languages
      arises from an independent and specific constraint on crossings. We provide
      statistical evidence suggesting that this is not the case, as the proportion of
      dependency crossings of sentences from a wide range of languages can be
      accurately estimated by a simple predictor based on a null hypothesis on the
      local probability that two dependencies cross given their lengths. The relative
      error of this predictor never exceeds 5% on average, whereas the error of a
      baseline predictor assuming a random ordering of the words of a sentence is at
      least six times greater. Our results suggest that the low frequency of crossings
      in natural languages is neither originated by hidden knowledge of language nor by
      the undesirability of crossings per se, but as a mere side effect of the
      principle of dependency length minimization.

PMID- 29347396
TI  - Diffusiophoresis in nonadsorbing polymer solutions: The Asakura-Oosawa model and
      stratification in drying films.
AB  - A colloidal particle placed in an inhomogeneous solution of smaller nonadsorbing
      polymers will move towards regions of lower polymer concentration in order to
      reduce the free energy of the interface between the surface of the particle and
      the solution. This phenomenon is known as diffusiophoresis. Treating the polymer
      as penetrable hard spheres, as in the Asakura-Oosawa model, a simple analytic
      expression for the diffusiophoretic drift velocity can be obtained. In the
      context of drying films we show that diffusiophoresis by this mechanism can lead
      to stratification under easily accessible experimental conditions. By
      stratification we mean spontaneous formation of a layer of polymer on top of a
      layer of the colloid. Transposed to the case of binary colloidal mixtures, this
      offers an explanation for the stratification observed recently in these systems
      [A. Fortini et al., Phys. Rev. Lett. 116, 118301 (2016)PRLTAO0031
      900710.1103/PhysRevLett.116.118301]. Our results emphasize the importance of
      treating solvent dynamics explicitly in these problems and caution against the
      neglect of hydrodynamic interactions or the use of implicit solvent models in
      which the absence of solvent backflow results in an unbalanced osmotic force that
      gives rise to large but unphysical effects.

PMID- 29347397
TI  - Maximum of an Airy process plus Brownian motion and memory in Kardar-Parisi-Zhang
      growth.
AB  - We obtain several exact results for universal distributions involving the maximum
      of the Airy_{2} process minus a parabola and plus a Brownian motion, with
      applications to the one-dimensional Kardar-Parisi-Zhang (KPZ) stochastic growth
      universality class. This allows one to obtain (i) the universal limit, for large
      time separation, of the two-time height correlation for droplet initial
      conditions, e.g., C_{infinity}=lim_{t_{2}/t_{1}->+infinity}h(t_{1})h(t_{2})[over 
      ]^{c}/h(t_{1})^{2}[over -]^{c}, with C_{infinity}~0.623, as well as conditional
      moments, which quantify ergodicity breaking in the time evolution; (ii) in the
      same limit, the distribution of the midpoint position x(t_{1}) of a directed
      polymer of length t_{2}; and (iii) the height distribution in stationary KPZ with
      a step. These results are derived from the replica Bethe ansatz for the KPZ
      continuum equation, with a "decoupling assumption" in the large time limit. They
      agree and confirm, whenever they can be compared, with (i) our recent tail
      results for two-time KPZ with the work by de Nardis and Le Doussal [J. Stat.
      Mech. (2017) 0532121742-546810.1088/1742-5468/aa6bce], checked in experiments
      with the work by Takeuchi and co-workers [De Nardis et al., Phys. Rev. Lett. 118,
      125701 (2017)PRLTAO0031-900710.1103/PhysRevLett.118.125701] and (ii) a recent
      result of Maes and Thiery [J. Stat. Phys. 168, 937 (2017)JSTPBS0022
      471510.1007/s10955-017-1839-2] on midpoint position.

PMID- 29347398
TI  - Forced underwater laminar flows with active magnetohydrodynamic metamaterials.
AB  - Theory and practical implementations for wake-free propulsion systems are
      proposed and proven with computational fluid dynamic modeling. Introduced
      earlier, the concept of active hydrodynamic metamaterials is advanced by
      introducing magnetohydrodynamic metamaterials, structures with custom-designed
      volumetric distribution of Lorentz forces acting on a conducting fluid.
      Distributions of volume forces leading to wake-free, laminar flows are designed
      using multivariate optimization. Theoretical indications are presented that such
      flows can be sustained at arbitrarily high Reynolds numbers. Moreover, it is
      shown that in the limit Re?10^{2}, a fixed volume force distribution may lead to
      a forced laminar flow across a wide range of Re numbers, without the need to
      reconfigure the force-generating metamaterial. Power requirements for such a
      device are studied as a function of the fluid conductivity. Implications to the
      design of distributed propulsion systems underwater and in space are discussed.

PMID- 29347399
TI  - Correlation between peak-height modulation and phase lapses in transport through
      quantum dots.
AB  - We show that two intriguing features of mesoscopic transport, namely, the
      modulation of Coulomb blockade peak heights and the transmission phase lapses
      occurring between subsequent peaks, are closely related. Our analytic arguments
      are corroborated by numerical simulations for chaotic ballistic quantum dots. The
      correlations between the two properties are experimentally testable. The
      statistical distribution of the partial-width amplitude, at the heart of the
      previous relationship, is determined, and its characteristic parameters are
      estimated from simple models.

PMID- 29347401
TI  - Transport on intermediate time scales in flows with cat's eye patterns.
AB  - We consider the advection-diffusion transport of tracers in a one-parameter
      family of plane periodic flows where the patterns of streamlines feature regions
      of confined circulation in the shape of "cat's eyes," separated by meandering
      jets with ballistic motion inside them. By varying the parameter, we proceed from
      the regular two-dimensional lattice of eddies without jets to the sinusoidally
      modulated shear flow without eddies. When a weak thermal noise is added, i.e., at
      large Peclet numbers, several intermediate time scales arise, with qualitatively
      and quantitatively different transport properties: depending on the parameter of
      the flow, the initial position of a tracer, and the aging time, motion of the
      tracers ranges from subdiffusive to superballistic. We report on results of
      extensive numerical simulations of the mean-squared displacement for different
      initial conditions in ordinary and aged situations. These results are compared
      with a theory based on a Levy walk that describes the intermediate-time ballistic
      regime and gives a reasonable description of the behavior for a certain class of
      initial conditions. The interplay of the walk process with internal circulation
      dynamics in the trapped state results at intermediate time scales in nonmonotonic
      characteristics of aging not captured by the Levy walk model.

PMID- 29347400
TI  - Disordered hyperuniformity in two-component nonadditive hard-disk plasmas.
AB  - We study the behavior of a classical two-component ionic plasma made up of
      nonadditive hard disks with additional logarithmic Coulomb interactions between
      them. Due to the Coulomb repulsion, long-wavelength total density fluctuations
      are suppressed and the system is globally hyperuniform. Short-range volume
      effects lead to phase separation or to heterocoordination for positive or
      negative nonadditivities, respectively. These effects compete with the hidden
      long-range order imposed by hyperuniformity. As a result, the critical behavior
      of the mixture is modified, with long-wavelength concentration fluctuations
      partially damped when the system is charged. It is also shown that the decrease
      of configurational entropy due to hyperuniformity originates from contributions
      beyond the two-particle level. Finally, despite global hyperuniformity, we show
      that in our system the spatial configuration associated with each component
      separately is not hyperuniform, i.e., the system is not "multihyperuniform."

PMID- 29347402
TI  - Stable lattice Boltzmann model for Maxwell equations in media.
AB  - : The present work shows a method for stable simulations via the lattice
      Boltzmann (LB) model for electromagnetic waves (EM) transiting homogeneous media.
      LB models for such media were already presented in the literature, but they
      suffer from numerical instability when the media transitions are sharp. We use
      one of these models in the limit of pure vacuum derived from Liu and Yan [Appl.
      Math. MODEL: 38, 1710 (2014)AMMODL0307-904X10.1016/j.apm.2013.09.009] and apply
      an extension that treats the effects of polarization and magnetization
      separately. We show simulations of simple examples in which EM waves travel into
      media to quantify error scaling, stability, accuracy, and time scaling. For
      conductive media, we use the Strang splitting and check the simulations accuracy
      at the example of the skin effect. Like pure EM propagation, the error for the
      static limits, which are constructed with a current density added in a first
      order scheme, can be less than 1%. The presented method is an easily implemented
      alternative for the stabilization of simulation for EM waves propagating in
      spatially complex structured media properties and arbitrary transitions.

PMID- 29347403
TI  - Influence of periodic external fields in multiagent models with language
      dynamics.
AB  - We investigate large-scale effects induced by external fields, phenomenologically
      interpreted as mass media, in multiagent models evolving with the microscopic
      dynamics of the binary naming game. In particular, we show that a single external
      field, broadcasting information at regular time intervals, can reverse the
      majority opinion of the population, provided the frequency and the effectiveness
      of the sent messages lie above well-defined thresholds. We study the phase
      structure of the model in the mean field approximation and in numerical
      simulations with several network topologies. We also investigate the influence on
      the agent dynamics of two competing external fields, periodically broadcasting
      different messages. In finite regions of the parameter space we observe periodic
      equilibrium states in which the average opinion densities are reversed with
      respect to naive expectations. Such equilibria occur in two cases: (i) when the
      frequencies of the competing messages are different but close to each other; (ii)
      when the frequencies are equal and the relative time shift of the messages does
      not exceed half a period. We interpret the observed phenomena as a result of the
      interplay between the external fields and the internal dynamics of the agents and
      conclude that, depending on the model parameters, the naming game is consistent
      with scenarios of first- or second-mover advantage (to borrow an expression from
      the jargon of business strategy).

PMID- 29347404
TI  - Scale-invariant Green-Kubo relation for time-averaged diffusivity.
AB  - In recent years it was shown both theoretically and experimentally that in
      certain systems exhibiting anomalous diffusion the time- and ensemble-averaged
      mean-squared displacement are remarkably different. The ensemble-averaged
      diffusivity is obtained from a scaling Green-Kubo relation, which connects the
      scale-invariant nonstationary velocity correlation function with the transport
      coefficient. Here we obtain the relation between time-averaged diffusivity,
      usually recorded in single-particle tracking experiments, and the underlying
      scale-invariant velocity correlation function. The time-averaged mean-squared
      displacement is given by <delta^{2}[over -]>~2D_{nu}t^{beta}Delta^{nu-beta},
      where t is the total measurement time and Delta is the lag time. Here nu is the
      anomalous diffusion exponent obtained from ensemble-averaged measurements
      <x^{2}>~t^{nu}, while beta>=-1 marks the growth or decline of the kinetic energy
      <v^{2}>~t^{beta}. Thus, we establish a connection between exponents that can be
      read off the asymptotic properties of the velocity correlation function and
      similarly for the transport constant D_{nu}. We demonstrate our results with
      nonstationary scale-invariant stochastic and deterministic models, thereby
      highlighting that systems with equivalent behavior in the ensemble average can
      differ strongly in their time average. If the averaged kinetic energy is finite,
      beta=0, the time scaling of <delta^{2}[over -]> and <x^{2}> are identical;
      however, the time-averaged transport coefficient D_{nu} is not identical to the
      corresponding ensemble-averaged diffusion constant.

PMID- 29347405
TI  - Revisiting universality of the liquid-gas critical point in two dimensions.
AB  - Critical point of liquid-gas (LG) transition does not conform with the paradigm
      of spontaneous symmetry breaking because there is no broken symmetry in both
      phases. We revisit the conjecture that this critical point belongs to the Ising
      class by performing large scale Monte Carlo simulations in two-dimensional free
      space in combination with the numerical flowgram method. Our main result is that
      the critical indices do agree with the Onsager values within the error of 1%-2%.
      This significantly improves the accuracy reported in the literature. The related
      problem about the role of higher order odd terms in the (real) phi^{4} field
      model as a mapping of the LG transition is addressed too. The scaling dimension
      of the phi^{5} term at criticality is shown to be the same as that of the linear
      one phi. We suggest that the role of all higher order odd terms at criticality is
      simply in generating the linear field operator with the critical dimension
      consistent with the Ising universality class.

PMID- 29347406
TI  - Fast inverse nonlinear Fourier transformation using exponential one-step methods:
      Darboux transformation.
AB  - This paper considers the non-Hermitian Zakharov-Shabat (ZS) scattering problem
      which forms the basis for defining the SU(2) nonlinear Fourier transformation
      (NFT). The theoretical underpinnings of this generalization of the conventional
      Fourier transformation are quite well established in the Ablowitz-Kaup-Newell
      Segur formalism; however, efficient numerical algorithms that could be employed
      in practical applications are still unavailable. In this paper, we present a
      unified framework for the forward and inverse NFT using exponential one-step
      methods which are amenable to FFT-based fast polynomial arithmetic. Within this
      discrete framework, we propose a fast Darboux transformation (FDT) algorithm
      having an operational complexity of O(KN+Nlog^{2}N) such that the error in the
      computed N-samples of the K-soliton vanishes as O(N^{-p}) where p is the order of
      convergence of the underlying one-step method. For fixed N, this algorithm
      outperforms the classical DT (CDT) algorithm which has a complexity of O(K^{2}N).
      We further present an extension of these algorithms to the general version of DT
      which allows one to add solitons to arbitrary profiles that are admissible as
      scattering potentials in the ZS problem. The general CDT and FDT algorithms have
      the same operational complexity as that of the K-soliton case and the order of
      convergence matches that of the underlying one-step method. A comparative study
      of these algorithms is presented through exhaustive numerical tests.

PMID- 29347407
TI  - Improved thermal lattice Boltzmann model for simulation of liquid-vapor phase
      change.
AB  - In this paper, an improved thermal lattice Boltzmann (LB) model is proposed for
      simulating liquid-vapor phase change, which is aimed at improving an existing
      thermal LB model for liquid-vapor phase change [S. Gong and P. Cheng, Int. J.
      Heat Mass Transfer 55, 4923 (2012)10.1016/j.ijheatmasstransfer.2012.04.037].
      First, we emphasize that the replacement of
      ?.(lambda?T)/?.(lambda?T)rhoc_{V}rhoc_{V} with ?.(chi?T) is an inappropriate
      treatment for diffuse interface modeling of liquid-vapor phase change.
      Furthermore, the error terms ?_{t_{0}}(Tv)+?.(Tvv), which exist in the
      macroscopic temperature equation recovered from the previous model, are
      eliminated in the present model through a way that is consistent with the
      philosophy of the LB method. Moreover, the discrete effect of the source term is
      also eliminated in the present model. Numerical simulations are performed for
      droplet evaporation and bubble nucleation to validate the capability of the model
      for simulating liquid-vapor phase change. It is shown that the numerical results
      of the improved model agree well with those of a finite-difference scheme.
      Meanwhile, it is found that the replacement of
      ?.(lambda?T)/?.(lambda?T)rhoc_{V}rhoc_{V} with ?.(chi?T) leads to significant
      numerical errors and the error terms in the recovered macroscopic temperature
      equation also result in considerable errors.

PMID- 29347408
TI  - Instabilities in rapid directional solidification under weak flow.
AB  - We examine a rapidly solidifying binary alloy under directional solidification
      with nonequilibrium interfacial thermodynamics viz. the segregation coefficient
      and the liquidus slope are speed dependent and attachment-kinetic effects are
      present. Both of these effects alone give rise to (steady) cellular
      instabilities, mode S, and a pulsatile instability, mode P. We examine how weak
      imposed boundary-layer flow of magnitude |V| affects these instabilities. For
      small |V|, mode S becomes a traveling and the flow stabilizes (destabilizes) the
      interface for small (large) surface energies. For small |V|, mode P has a
      critical wave number that shifts from zero to nonzero giving spatial structure.
      The flow promotes this instability and the frequencies of the complex conjugate
      pairs each increase (decrease) with flow for large (small) wave numbers. These
      results are obtained by regular perturbation theory in powers of V far from the
      point where the neutral curves cross, but requires a modified expansion in powers
      of V^{1/3} near the crossing. A uniform composite expansion is then obtained
      valid for all small |V|.

PMID- 29347409
TI  - Bulk and local rheology in a dense and vibrated granular suspension.
AB  - In this paper, we investigate experimentally the dynamics of particles in dense
      granular suspensions when both shear and external vibrations are applied. We
      study in detail how vibrations affect particle reorganization at the local scale
      and modify the apparent rheology. The nonlocal nature of the rheology when no
      vibrations are applied is evidenced, in agreement with previous numerical studies
      from the literature. It is also shown that vibrations induce structural
      reorganizations, which tend to homogenize the system and cancel the nonlocal
      properties.

PMID- 29347410
TI  - Mode-coupling theory for active Brownian particles.
AB  - We present a mode-coupling theory (MCT) for the slow dynamics of two-dimensional
      spherical active Brownian particles (ABPs). The ABPs are characterized by a self
      propulsion velocity v_{0} and by their translational and rotational diffusion
      coefficients D_{t} and D_{r}, respectively. Based on the integration-through
      transients formalism, the theory requires as input only the equilibrium static
      structure factors of the passive system (where v_{0}=0). It predicts a nontrivial
      idealized-glass-transition diagram in the three-dimensional parameter space of
      density, self-propulsion velocity, and rotational diffusivity that arise because
      at high densities, the persistence length of active swimming l_{p}=v_{0}/D_{r}
      interferes with the interaction length l_{c} set by the caging of particles.
      While the low-density dynamics of ABPs is characterized by a single Peclet number
      Pe=v_{0}^{2}/D_{r}D_{t}, close to the glass transition the dynamics is found to
      depend on Pe and l_{p} separately. At fixed density, increasing the self
      propulsion velocity causes structural relaxation to speed up, while decreasing
      the persistence length slows down the relaxation. The active-MCT glass is a
      nonergodic state that is qualitatively different from the passive glass. In it,
      correlations of initial density fluctuations never fully decay, but also an
      infinite memory of initial orientational fluctuations is retained in the
      positions.

PMID- 29347411
TI  - Complete analysis of ensemble inequivalence in the Blume-Emery-Griffiths model.
AB  - We study inequivalence of canonical and microcanonical ensembles in the mean
      field Blume-Emery-Griffiths model. This generalizes previous results obtained for
      the Blume-Capel model. The phase diagram strongly depends on the value of the
      biquadratic exchange interaction K, the additional feature present in the Blume
      Emery-Griffiths model. At small values of K, as for the Blume-Capel model, lines
      of first- and second-order phase transitions between a ferromagnetic and a
      paramagnetic phase are present, separated by a tricritical point whose location
      is different in the two ensembles. At higher values of K the phase diagram
      changes substantially, with the appearance of a triple point in the canonical
      ensemble, which does not find any correspondence in the microcanonical ensemble.
      Moreover, one of the first-order lines that starts from the triple point ends in
      a critical point, whose position in the phase diagram is different in the two
      ensembles. This line separates two paramagnetic phases characterized by a
      different value of the quadrupole moment. These features were not previously
      studied for other models and substantially enrich the landscape of ensemble
      inequivalence, identifying new aspects that had been discussed in a
      classification of phase transitions based on singularity theory. Finally, we
      discuss ergodicity breaking, which is highlighted by the presence of gaps in the
      accessible values of magnetization at low energies: it also displays new
      interesting patterns that are not present in the Blume-Capel model.

PMID- 29347412
TI  - Observation of structural universality in disordered systems using bulk diffusion
      measurement.
AB  - We report on an experimental observation of classical diffusion distinguishing
      between structural universality classes of disordered systems in one dimension.
      Samples of hyperuniform and short-range disorder were designed, characterized by
      the statistics of the placement of micrometer-thin parallel permeable barriers,
      and the time-dependent diffusion coefficient was measured by NMR methods over
      three orders of magnitude in time. The relation between the structural exponent,
      characterizing disorder universality class, and the dynamical exponent of the
      diffusion coefficient is experimentally verified. The experimentally established
      relation between structure and transport exemplifies the hierarchical nature of
      structural complexity-dynamics are mainly determined by the universality class,
      whereas microscopic parameters affect the nonuniversal coefficients. These
      results open the way for noninvasive characterization of structural correlations
      in porous media, complex materials, and biological tissues via a bulk diffusion
      measurement.

PMID- 29347413
TI  - Off-diagonal expansion quantum Monte Carlo.
AB  - We propose a Monte Carlo algorithm designed to simulate quantum as well as
      classical systems at equilibrium, bridging the algorithmic gap between quantum
      and classical thermal simulation algorithms. The method is based on a
      decomposition of the quantum partition function that can be viewed as a series
      expansion about its classical part. We argue that the algorithm not only provides
      a theoretical advancement in the field of quantum Monte Carlo simulations, but is
      optimally suited to tackle quantum many-body systems that exhibit a range of
      behaviors from "fully quantum" to "fully classical," in contrast to many existing
      methods. We demonstrate the advantages, sometimes by orders of magnitude, of the
      technique by comparing it against existing state-of-the-art schemes such as path
      integral quantum Monte Carlo and stochastic series expansion. We also illustrate
      how our method allows for the unification of quantum and classical thermal
      parallel tempering techniques into a single algorithm and discuss its practical
      significance.

PMID- 29347414
TI  - Dynamical density functional theory analysis of the laning instability in sheared
      soft matter.
AB  - Using dynamical density functional theory (DDFT) methods we investigate the
      laning instability of a sheared colloidal suspension. The nonequilibrium ordering
      at the laning transition is driven by nonaffine particle motion arising from
      interparticle interactions. Starting from a DDFT which incorporates the nonaffine
      motion, we perform a linear stability analysis that enables identification of the
      regions of parameter space where lanes form. We illustrate our general approach
      by applying it to a simple one-component fluid of soft penetrable particles.

PMID- 29347415
TI  - Possible mechanism for aligning microscopic flexible filaments predicted using
      "caterpillar" hydrodynamics.
AB  - We use the "caterpillar" model for accurately calculating the inhomogeneous
      hydrodynamic friction along a microscopic slender cylindrical filaments using
      Oseen level hydrodynamics. The methodology is applied to study the motion of a
      flexible filament in a circularly polarized field. Our results predict that in
      dilute solution alignment occurs along the axis of the field. For electric
      fields, the strengths and frequencies required are deduced. These are
      experimentally accessible. We therefore propose that this is a practical method
      for aligning filaments such as microtubules and functionalized carbon nanotubes.

PMID- 29347416
TI  - Computational framework for particle and spin simulations based on the stochastic
      Galerkin method.
AB  - An implementation of the polynomial chaos expansion is introduced as a fast
      solver of the equations of beam and spin motion of charged particles in
      electromagnetic fields. We show that, based on the stochastic Galerkin method,
      our computational framework substantially reduces the required number of tracking
      calculations compared to the widely used Monte Carlo method.

PMID- 29347417
TI  - Exact solution of the critical Ising model with special toroidal boundary
      conditions.
AB  - The Ising model in two dimensions with special toroidal boundary conditions is
      analyzed. These boundary conditions, which we call duality-twisted boundary
      conditions, may be interpreted as inserting a specific defect line ("seam") in
      the system, along noncontractible circles of the cylinder, before closing it into
      a torus. We derive exact expressions for the eigenvalues of a transfer matrix for
      the critical ferromagnetic Ising model on the M*N square lattice wrapped on the
      torus with a specific defect line. As a result we have obtained analytically the
      partition function for the Ising model with such boundary conditions. In the case
      of infinitely long cylinders of circumference L with duality-twisted boundary
      conditions we obtain the asymptotic expansion of the free energy and the inverse
      correlation lengths. We find that the ratio of subdominant finite-size correction
      terms in the asymptotic expansion of the free energy and the inverse correlation
      lengths should be universal. We verify such universal behavior in the framework
      of a perturbating conformal approach by calculating the universal structure
      constant C_{n1n} for descendent states generated by the operator product
      expansion of the primary fields. For such states the calculations of an universal
      structure constants is a difficult task, since it involves knowledge of the four
      point correlation function, which in general is not fixed by conformal invariance
      except for some particular cases, including the Ising model.

PMID- 29347418
TI  - Preconditioned lattice Boltzmann method for steady flows: A noncascaded central
      moments-based approach.
AB  - We present a concise yet effective central-moments-based lattice Boltzmann method
      with an accelerated convergence to the steady state through preconditioning. It
      is demonstrated that the proposed scheme reduces to a slight modification of the
      unaccelerated one, as the preconditioning affects only the equilibrium state.
      Different from previous efforts carried out within the lattice Boltzmann
      community, the present scheme is built on an original model. In fact, the
      corresponding collision operator loses the pyramidal orchestrated nature that is
      typical of the cascaded scheme, hence we coin the name "noncascaded." Our model
      is very general, characterized by highly intelligible formulations, simple to
      implement, and it can be derived for any lattice velocity space.

PMID- 29347419
TI  - Diverging, but negligible power at Carnot efficiency: Theory and experiment.
AB  - We discuss the possibility of reaching the Carnot efficiency by heat engines
      (HEs) out of quasistatic conditions at nonzero power output. We focus on several
      models widely used to describe the performance of actual HEs. These models
      comprise quantum thermoelectric devices, linear irreversible HEs, minimally
      nonlinear irreversible HEs, HEs working in the regime of low-dissipation,
      overdamped stochastic HEs and an underdamped stochastic HE. Although some of
      these HEs can reach the Carnot efficiency at nonzero and even diverging power,
      the magnitude of this power is always negligible compared to the maximum power
      attainable in these systems. We provide conditions for attaining the Carnot
      efficiency in the individual models and explain practical aspects connected with
      reaching the Carnot efficiency at large power output. Furthermore, we show how
      our findings can be tested in practice using a standard Brownian HE realizable
      with available micromanipulation techniques.

PMID- 29347420
TI  - Bayesian inference with information content model check for Langevin equations.
AB  - The Bayesian data analysis framework has been proven to be a systematic and
      effective method of parameter inference and model selection for stochastic
      processes. In this work, we introduce an information content model check that may
      serve as a goodness-of-fit, like the chi^{2} procedure, to complement
      conventional Bayesian analysis. We demonstrate this extended Bayesian framework
      on a system of Langevin equations, where coordinate-dependent mobilities and
      measurement noise hinder the normal mean-squared displacement approach.

PMID- 29347421
TI  - Turing-like structures in a functional model of cortical spreading depression.
AB  - Cortical spreading depression (CSD) along with migraine waves and spreading
      depolarization events with stroke or injures are the front-line examples of
      extreme physiological behaviors of the brain cortex which manifest themselves via
      the onset and spreading of localized areas of neuronal hyperactivity followed by
      their depression. While much is known about the physiological pathways involved,
      the dynamical mechanisms of the formation and evolution of complex spatiotemporal
      patterns during CSD are still poorly understood, in spite of the number of
      modeling studies that have been already performed. Recently we have proposed a
      relatively simple mathematical model of cortical spreading depression which
      counts the effects of neurovascular coupling and cerebral blood flow
      redistribution during CSD. In the present study, we address the main dynamical
      consequences of newly included pathways, namely, the changes in the formation and
      propagation speed of the CSD front and the pattern formation features in two
      dimensions. Our most notable finding is that the combination of vascular-mediated
      spatial coupling with local regulatory mechanisms results in the formation of
      stationary Turing-like patterns during a CSD event.

PMID- 29347422
TI  - Periodicity in the autocorrelation function as a mechanism for regularly
      occurring zero crossings or extreme values of a Gaussian process.
AB  - The problem of zero crossings is of great historical prevalence and promises
      extensive application. The challenge is to establish precisely how the
      autocorrelation function or power spectrum of a one-dimensional continuous random
      process determines the density function of the intervals between the zero
      crossings of that process. This paper investigates the case where periodicities
      are incorporated into the autocorrelation function of a smooth process. Numerical
      simulations, and statistics about the number of crossings in a fixed interval,
      reveal that in this case the zero crossings segue between a random and
      deterministic point process depending on the relative time scales of the periodic
      and nonperiodic components of the autocorrelation function. By considering the
      Laplace transform of the density function, we show that incorporating correlation
      between successive intervals is essential to obtaining accurate results for the
      interval variance. The same method enables prediction of the density function
      tail in some regions, and we suggest approaches for extending this to cover all
      regions. In an ever-more complex world, the potential applications for this scale
      of regularity in a random process are far reaching and powerful.

PMID- 29347423
TI  - Rayleigh-Taylor instability in accelerated elastic-solid slabs.
AB  - We develop the linear theory for the asymptotic growth of the incompressible
      Rayleigh-Taylor instability of an accelerated solid slab of density rho_{2},
      shear modulus G, and thickness h, placed over a semi-infinite ideal fluid of
      density rho_{1}<rho_{2}. It extends previous results for Atwood number A_{T}=1
      [B. J. Plohr and D. H. Sharp, Z. Angew. Math. Phys. 49, 786 (1998)ZAMPA80044
      227510.1007/s000330050121] to arbitrary values of A_{T} and unveil the singular
      feature of an instability threshold below which the slab is stable for any
      perturbation wavelength. As a consequence, an accelerated elastic-solid slab is
      stable if rho_{2}gh/G<=2(1-A_{T})/A_{T}.

PMID- 29347424
TI  - Topology effects on nonaffine behavior of semiflexible fiber networks.
AB  - Filamentous semiflexible networks define the mechanical and physical properties
      of many materials such as cytoskeleton. In the absence of a distinct unit cell,
      the Mikado fiber network model is commonly used algorithm for representing the
      microstructure of these networks in numerical models. Nevertheless, certain types
      of filamentous structures such as collagenous tissues, at early stages of their
      development, are assembled by growth of individual fibers from random nucleation
      sites. In this work, we develop a computational model to investigate the
      mechanical response of such networks by characterizing their nonaffine behavior.
      We show that the deformation of these networks is nonaffine at all length scales.
      Furthermore, similar to Mikado networks, the degree of nonaffinity in these
      structures decreases with increasing the probing length scale, the network fiber
      density, and/or the bending stiffness of constituting filaments. Nevertheless,
      despite the lower coordination number of these networks, their deformation field
      is more affine than that of the Mikado networks with the same fiber density and
      fiber mechanical properties.

PMID- 29347425
TI  - Entanglement transitions induced by large deviations.
AB  - The probability of large deviations of the smallest Schmidt eigenvalue for random
      pure states of bipartite systems, denoted as A and B, is computed analytically
      using a Coulomb gas method. It is shown that this probability, for large N, goes
      as exp[-betaN^{2}Phi(zeta)], where the parameter beta is the Dyson index of the
      ensemble, zeta is the large deviation parameter, while the rate function
      Phi(zeta) is calculated exactly. Corresponding equilibrium Coulomb charge density
      is derived for its large deviations. Effects of the large deviations of the
      extreme (largest and smallest) Schmidt eigenvalues on the bipartite entanglement
      are studied using the von Neumann entropy. Effect of these deviations is also
      studied on the entanglement between subsystems 1 and 2, obtained by further
      partitioning the subsystem A, using the properties of the density matrix's
      partial transpose rho_{12}^{Gamma}. The density of states of rho_{12}^{Gamma} is
      found to be close to the Wigner's semicircle law with these large deviations. The
      entanglement properties are captured very well by a simple random matrix model
      for the partial transpose. The model predicts the entanglement transition across
      a critical large deviation parameter zeta. Log negativity is used to quantify the
      entanglement between subsystems 1 and 2. Analytical formulas for it are derived
      using the simple model. Numerical simulations are in excellent agreement with the
      analytical results.

PMID- 29347426
TI  - Dynamic induced softening in frictional granular materials investigated by
      discrete-element-method simulation.
AB  - A granular system composed of frictional glass beads is simulated using the
      discrete element method. The intergrain forces are based on the Hertz contact law
      in the normal direction with frictional tangential force. The damping due to
      collision is also accounted for. Systems are loaded at various stresses and their
      quasistatic elastic moduli are characterized. Each system is subjected to an
      extensive dynamic testing protocol by measuring the resonant response to a broad
      range of ac drive amplitudes and frequencies via a set of diagnostic strains. The
      system, linear at small ac drive amplitudes, has resonance frequencies that shift
      downward (i.e., modulus softening) with increased ac drive amplitude. Detailed
      testing shows that the slipping contact ratio does not contribute significantly
      to this dynamic modulus softening, but the coordination number is strongly
      correlated to this reduction. This suggests that the softening arises from the
      extended structural change via break and remake of contacts during the
      rearrangement of bead positions driven by the ac amplitude.

PMID- 29347427
TI  - Effect of an external field on capillary waves in a dipolar fluid.
AB  - The role of an external field on capillary waves at the liquid-vapor interface of
      a dipolar fluid is investigated using molecular dynamics simulations. For fields
      parallel to the interface, the interfacial width squared increases linearly with
      respect to the logarithm of the size of the interface across all field strengths
      tested. The value of the slope decreases with increasing field strength,
      indicating that the field dampens the capillary waves. With the inclusion of the
      parallel field, the surface stiffness increases with increasing field strength
      faster than the surface tension. For fields perpendicular to the interface, the
      interfacial width squared is linear with respect to the logarithm of the size of
      the interface for small field strengths, and the surface stiffness is less than
      the surface tension. Above a critical field strength that decreases as the size
      of the interface increases, the interface becomes unstable due to the increased
      amplitude of the capillary waves.

PMID- 29347428
TI  - Allison mixture and the two-envelope problem.
AB  - In the present study, we have investigated the Allison mixture, a variant of the
      Parrondo's games where random mixing of two random sequences creates
      autocorrelation. We have obtained the autocorrelation function and mutual entropy
      of two elements. Our analysis shows that the mutual information is nonzero even
      if two distributions have identical average values. We have also considered the
      two-envelope problem and solved for its exact probability distribution.

PMID- 29347429
TI  - Collapse transition in polymer models with multiple monomers per site and
      multiple bonds per edge.
AB  - We present results from extensive Monte Carlo simulations of polymer models where
      each lattice site can be visited by up to K monomers and no restriction is
      imposed on the number of bonds on each lattice edge. These multiple monomer per
      site (MMS) models are investigated on the square and cubic lattices, for K=2 and
      3, by associating Boltzmann weights omega_{0}=1, omega_{1}=e^{beta_{1}}, and
      omega_{2}=e^{beta_{2}} to sites visited by 1, 2, and 3 monomers, respectively.
      Two versions of the MMS models are considered for which immediate reversals of
      the walks are allowed (RA) or forbidden (RF). In contrast to previous simulations
      of these models, we find the same thermodynamic behavior for both RA and RF
      versions. In three dimensions, the phase diagrams, in space beta_{2}*beta_{1},
      are featured by coil and globule phases separated by a line of Theta points, as
      thoroughly demonstrated by the metric nu_{t}, crossover phi_{t}, and entropic
      gamma_{t} exponents. The existence of the Theta lines is also confirmed by the
      second virial coefficient. This shows that no discontinuous collapse transition
      exists in these models, in contrast to previous claims based on a weak bimodality
      observed in some distributions, which indeed exists in a narrow region very close
      to the Theta line when beta_{1}<0. Interestingly, in two dimensions, only a
      crossover is found between the coil and globule phases.

PMID- 29347430
TI  - Fluctuation correlation models for receptor immobilization.
AB  - Nanoscale dynamics with cycles of receptor diffusion and immobilization by cell
      external-or-internal factors is a key process in living cell adhesion phenomena
      at the origin of a plethora of signal transduction pathways. Motivated by modern
      correlation microscopy approaches, the receptor correlation functions in physical
      models based on diffusion-influenced reaction is studied. Using analytical and
      stochastic modeling, this paper focuses on the hybrid regime where diffusion and
      reaction are not truly separable. The time receptor autocorrelation functions are
      shown to be indexed by different time scales and their asymptotic expansions are
      given. Stochastic simulations show that this analysis can be extended to
      situations with a small number of molecules. It is also demonstrated that this
      analysis applies when receptor immobilization is coupled to environmental noise.

PMID- 29347431
TI  - Bending energy of buckled edge dislocations.
AB  - The study of elastic membranes carrying topological defects has a longstanding
      history, going back at least to the 1950s. When allowed to buckle in three
      dimensional space, membranes with defects can totally relieve their in-plane
      strain, remaining with a bending energy, whose rigidity modulus is small compared
      to the stretching modulus. In this paper we study membranes with a single edge
      dislocation. We prove that the minimum bending energy associated with strain-free
      configurations diverges logarithmically with the size of the system.

PMID- 29347432
TI  - Lattice diffusion of a single molecule in solution.
AB  - The ability to trap a single molecule in an electrostatic potential well in
      solution has opened up new possibilities for the use of molecular electrical
      charge to study macromolecular conformation and dynamics at the level of the
      single entity. Here we study the diffusion of a single macromolecule in a two
      dimensional lattice of electrostatic traps in solution. We report the ability to
      measure both the size and effective electrical charge of a macromolecule by
      observing single-molecule transport trajectories, typically a few seconds in
      length, using fluorescence microscopy. While, as shown previously, the time spent
      by the molecule in a trap is a strong function of its effective charge, we
      demonstrate here that the average travel time between traps in the landscape
      yields its hydrodynamic radius. Tailoring the pitch of the lattice thus yields
      two different experimentally measurable time scales that together uniquely
      determine both the size and charge of the molecule. Since no information is
      required on the location of the molecule between consecutive departure and
      arrival events at lattice sites, the technique is ideally suited to measurements
      on weakly emitting entities such as single molecules.

PMID- 29347433
TI  - Integral representation of channel flow with interacting particles.
AB  - We construct a boundary integral representation for the low-Reynolds-number flow
      in a channel in the presence of freely suspended particles (or droplets) of
      arbitrary size and shape. We demonstrate that lubrication theory holds away from
      the particles at horizontal distances exceeding the channel height and derive a
      multipole expansion of the flow which is dipolar to the leading approximation. We
      show that the dipole moment of an arbitrary particle is a weighted integral of
      the stress and the flow at the particle surface, which can be determined
      numerically. We introduce the equation of motion that describes hydrodynamic
      interactions between arbitrary, possibly different, distant particles, with
      interactions determined by the product of the mobility matrix and the dipole
      moment. Further, the problem of three identical interacting spheres initially
      aligned in the streamwise direction is considered and the experimentally observed
      "pair exchange" phenomenon is derived analytically and confirmed numerically. For
      nonaligned particles, we demonstrate the formation of a configuration with one
      particle separating from a stable pair. Our results suggest that in a dilute
      initially homogenous particulate suspension flowing in a channel the particles
      will eventually separate into singlets and pairs.

PMID- 29347434
TI  - Thermalized formulation of soft glassy rheology.
AB  - We present a version of soft glassy rheology that includes thermalized strain
      degrees of freedom. It fully specifies systems' strain-history-dependent
      positions on their energy landscapes and therefore allows for quantitative
      analysis of their heterogeneous yielding dynamics and nonequilibrium deformation
      thermodynamics. As a demonstration of the method, we illustrate the very
      different characteristics of fully thermal and nearly athermal plasticity by
      comparing results for thermalized and nonthermalized plastic flow.

PMID- 29347435
TI  - Three faces of node importance in network epidemiology: Exact results for small
      graphs.
AB  - We investigate three aspects of the importance of nodes with respect to
      susceptible-infectious-removed (SIR) disease dynamics: influence maximization
      (the expected outbreak size given a set of seed nodes), the effect of vaccination
      (how much deleting nodes would reduce the expected outbreak size), and sentinel
      surveillance (how early an outbreak could be detected with sensors at a set of
      nodes). We calculate the exact expressions of these quantities, as functions of
      the SIR parameters, for all connected graphs of three to seven nodes. We obtain
      the smallest graphs where the optimal node sets are not overlapping. We find that
      (i) node separation is more important than centrality for more than one active
      node, (ii) vaccination and influence maximization are the most different aspects
      of importance, and (iii) the three aspects are more similar when the infection
      rate is low.

PMID- 29347436
TI  - Quantification of tension to explain bias dependence of driven polymer
      translocation dynamics.
AB  - Motivated by identifying the origin of the bias dependence of tension
      propagation, we investigate methods for measuring tension propagation
      quantitatively in computer simulations of driven polymer translocation. Here, the
      motion of flexible polymer chains through a narrow pore is simulated using
      Langevin dynamics. We measure tension forces, bead velocities, bead distances,
      and bond angles along the polymer at all stages of translocation with
      unprecedented precision. Measurements are done at a standard temperature used in
      simulations and at zero temperature to pin down the effect of fluctuations. The
      measured quantities were found to give qualitatively similar characteristics, but
      the bias dependence could be determined only using tension force. We find that in
      the scaling relation tau~N^{beta}f_{d}^{alpha} for translocation time tau, the
      polymer length N, and the bias force f_{d}, the increase of the exponent beta
      with bias is caused by center-of-mass diffusion of the polymer toward the pore on
      the cis side. We find that this diffusion also causes the exponent alpha to
      deviate from the ideal value -1. The bias dependence of beta was found to result
      from combination of diffusion and pore friction and so be relevant for polymers
      that are too short to be considered asymptotically long. The effect is relevant
      in experiments all of which are made using polymers whose lengths are far below
      the asymptotic limit. Thereby, our results also corroborate the theoretical
      prediction by Sakaue's theory [Polymers 8, 424 (2016)2073
      436010.3390/polym8120424] that there should not be bias dependence of beta for
      asymptotically long polymers. By excluding fluctuations we also show that monomer
      crowding at the pore exit cannot have a measurable effect on translocation
      dynamics under realistic conditions.

PMID- 29347437
TI  - Mechanisms of cooperation and competition of two-species transport in narrow
      nanochannels.
AB  - Flow of particles of two different species through a narrow channel with solely
      two discrete spatial positions is analyzed with respect to the species'
      capability to cooperate or compete for transport. The origin of the latter arises
      from particle-channel and interparticle interactions within the channel, i.e.,
      blocking the position of a particle, and its interaction with its neighbors in
      the channel. The variety of occupation options within the channel defines the
      state space. The transition dynamics within is considered as a continuous Markov
      process, which, in contrast to mean-field approaches, conserves explicitly
      spatial correlations. A strong repulsive interaction between particles of the
      same kind and a very attractive empty channel imply a strong entanglement of
      transport of both species. In the limiting case of perfect coupling, flows in
      state space are restricted to a cyclic subspace, where they become all equivalent
      in the steady state. In particular, this implies equal particle flows of the two
      species. Entanglement of transport implies that the species mutually exert
      entropic forces on each other. For parallel directed concentration gradients this
      implies that the species' ability to cooperate increases with the degree of
      entanglement. Thus, the gradient of one species reciprocally induces a higher
      flow of the other species when compared to that in its absence. The opposite
      holds for antiparallel gradients where species mutually hamper their transport.
      For a sufficient strong coupling, the species under the influence of the stronger
      concentration gradient drives the other against its gradient, i.e., the positive
      mixing entropy production of the driving species becomes the motor for the
      negative mixing entropy production of the driven one. The degree of effectiveness
      by which negative entropy production emerges at the cost of positive entropy
      production increases with the coupling strength. This becomes evident from
      location and connectivity of the sources of entropy production in state space.

PMID- 29347438
TI  - Spatial shape of avalanches.
AB  - In disordered elastic systems, driven by displacing a parabolic confining
      potential adiabatically slowly, all advance of the system is in bursts, termed
      avalanches. Avalanches have a finite extension in time, which is much smaller
      than the waiting time between them. Avalanches also have a finite extension l in
      space, i.e., only a part of the interface of size l moves during an avalanche.
      Here we study their spatial shape <S(x)>_{l} given l, as well as its fluctuations
      encoded in the second cumulant <S^{2}(x)>_{l}^{c}. We establish scaling relations
      governing the behavior close to the boundary. We then give analytic results for
      the Brownian force model, in which the microscopic disorder for each degree of
      freedom is a random walk. Finally, we confirm these results with numerical
      simulations. To do this properly we elucidate the influence of discretization
      effects, which also confirms the assumptions entering into the scaling ansatz.
      This allows us to reach the scaling limit already for avalanches of moderate
      size. We find excellent agreement for the universal shape and its fluctuations,
      including all amplitudes.

PMID- 29347439
TI  - Quantum effects and quantum chaos in multidimensional tunneling.
AB  - The ground-state energy splitting due to tunneling in two-dimensional double
      wells of the form V(x,y)=(x^{2}-R^{2})^{2}/8R^{2}+x^{2}
      R^{2}/R^{2}gammay+omega^{2}/2y^{2} is calculated. Several results are reported.
      First, we give a systematic WKB expansion of the splitting in series in powers of
      R^{-2}, each term of the series being a finite polynomial in gamma^{2}. We find
      an ascending sequence of the values of the parameter gamma characterizing the
      curvature of the classical path, for which the successive corrections to the
      leading order vanish. This effect arises because curvature of the path and
      quantum nature of motion cancel each other; it does not appear for one
      dimensional double wells. Second, we find that for large curvatures, such as for
      those describing the proton transfer in a malonaldehyde and hydroxalate anion,
      this expansion is of no practical use. Thus, the WKB expansion is reordered to a
      strong coupling form, each term of the series in powers of R^{-2} being an
      infinite series in powers of gamma[over -]^{2}, gamma[over -]=gamma/R. Third, we
      find that the radius of convergence of the series is determined by the
      singularity at gamma[over -]_{s}=omega/2. At the singularity the system changes
      its character from being a double well to become a single well. Close to this
      singularity the classical action and its first quantum correction are found to be
      nonanalytic functions of gamma[over -], most likely of the form [1-(gamma[over 
      ]/gamma[over -]_{s})^{2}]^{alpha}, where alpha=1/2 and alpha=-1/2 for the
      classical action and its first quantum correction, respectively. Since in the
      semiclassical regime of large R the splitting is exponentially dependent on the
      value of the classical action and its first quantum correction, close to the
      singularity we establish strong sensitivity of the splitting on slight variations
      of the parameter gamma[over -] entering the Hamiltonian linearly.

PMID- 29347440
TI  - Cooling beyond the boundary value in supercritical fluids under vibration.
AB  - Supercritical fluids when subjected to simultaneous quench and vibration have
      been known to cause various intriguing flow phenomena and instabilities depending
      on the relative direction of temperature gradient and vibration. Here we describe
      a surprising and interesting phenomenon wherein temperature in the fluid falls
      below the imposed boundary value when the walls are quenched and the direction of
      vibration is normal to the temperature gradient. We define these regions in the
      fluid as sink zones, because they act like sink for heat within the fluid domain.
      The formation of these zones is first explained using a one-dimensional (1D)
      analysis with acceleration in constant direction. Subsequently, the effect of
      various boundary conditions and the relative direction of the temperature
      gradient to acceleration are analyzed, highlighting the necessary conditions for
      the formation of sink zones. It is found that the effect of high compressibility
      and the action of self-weight (due to high acceleration) causes the temperature
      to change in the bulk besides the usual action of piston effect. This
      subsequently affects the overall temperature profile thereby leading to the
      formation of sink zones. Though the examined 1D cases differ from the current two
      dimensional (2D) cases, owing to the direction of acceleration being normal as
      compared to parallel in case of former, the explanations pertaining to 1D cases
      are judiciously utilized to elucidate the formation of sink zones in 2D
      supercritical fluids subjected to thermal quench and vibrational acceleration.
      The appearance of sink zones is found to be dependent on several factors such as
      proximity to the critical point and acceleration. A surface three-dimensional
      plot illustrating the effect of these parameters on onset time of sink zones is
      presented to further substantiate these arguments.

PMID- 29347441
TI  - Geometrical interpretation of dynamical phase transitions in boundary-driven
      systems.
AB  - Dynamical phase transitions are defined as nonanalytic points of the large
      deviation function of current fluctuations. We show that for boundary-driven
      systems, many dynamical phase transitions can be identified using the geometrical
      structure of an effective potential of a Hamiltonian, recovered from the
      macroscopic fluctuation theory description. Using this method we identify new
      dynamical phase transitions that could not be recovered using existing
      perturbative methods. Moreover, using the Hamiltonian picture, an experimental
      scheme is suggested to demonstrate an analog of dynamical phase transitions in
      linear, rather than exponential, time.

PMID- 29347442
TI  - Influence of ligand-receptor interactions on force-extension behavior within the
      freely jointed chain model.
AB  - We study the influence of receptor-ligand interactions on the force response of
      single polymer chains theoretically. The extension of the chain is modeled in
      terms of freely jointed chain or elastic freely jointed chain (EFJC) models. The
      situation involving noninteracting bonds is solved exactly, while effects of
      interactions are treated within a mean-field approximation. The form with shorter
      bonds governs the low force situation, while the form with longer bonds is
      relevant in the high force regime. We further discuss the accuracy of approximate
      relations, which were used to describe the response of the EFJC model.

PMID- 29347443
TI  - Microcanonical Szilard engines beyond the quasistatic regime.
AB  - We discuss the possibility of extracting energy from a single thermal bath using
      microcanonical Szilard engines operating in finite time. This extends previous
      works on the topic which are restricted to the quasistatic regime. The feedback
      protocol is implemented based on linear response predictions of the excess work.
      It is claimed that the underlying mechanism leading to energy extraction does not
      violate Liouville's theorem and preserves ergodicity throughout the cycle. We
      illustrate our results with several examples including an exactly solvable model.

PMID- 29347444
TI  - Theoretical study of the effect of pi^{+}-pi^{+} association in imidazolium ionic
      liquids at charged interfaces.
AB  - We develop an extended classical density-functional theory to describe clustering
      of imidazolium-based cations into linear chains, driven by pi-pi stacking. We
      find that the associating system displays a similar short-ranged structure to the
      completely dissociated fluid. We also construct a restricted primitive model for
      associating ionic species in an RTIL+solvent mixture. The double-layer formed in
      these systems exhibits strong overscreening by the cation chains, as expected.
      Significantly enhanced capacitance is also observed for the case where
      counterions are the associating species. The established density-functional
      method can be also used to describe polydisperse polyelectrolyte models.

PMID- 29347445
TI  - Mobility-induced persistent chimera states.
AB  - We study the dynamics of mobile, locally coupled identical oscillators in the
      presence of coupling delays. We find different kinds of chimera states in which
      coherent in-phase and antiphase domains coexist with incoherent domains. These
      chimera states are dynamic and can persist for long times for intermediate
      mobility values. We discuss the mechanisms leading to the formation of these
      chimera states in different mobility regimes. This finding could be relevant for
      natural and technological systems composed of mobile communicating agents.

PMID- 29347446
TI  - Diffusing-wave spectroscopy in a standard dynamic light scattering setup.
AB  - Diffusing-wave spectroscopy (DWS) extends dynamic light scattering measurements
      to samples with strong multiple scattering. DWS treats the transport of photons
      through turbid samples as a diffusion process, thereby making it possible to
      extract the dynamics of scatterers from measured correlation functions. The
      analysis of DWS data requires knowledge of the path length distribution of
      photons traveling through the sample. While for flat sample cells this path
      length distribution can be readily calculated and expressed in analytical form;
      no such expression is available for cylindrical sample cells. DWS measurements
      have therefore typically relied on dedicated setups that use flat sample cells.
      Here we show how DWS measurements, in particular DWS-based microrheology
      measurements, can be performed in standard dynamic light scattering setups that
      use cylindrical sample cells. To do so we perform simple random-walk simulations
      that yield numerical predictions of the path length distribution as a function of
      both the transport mean free path and the detection angle. This information is
      used in experiments to extract the mean-square displacement of tracer particles
      in the material, as well as the corresponding frequency-dependent viscoelastic
      response. An important advantage of our approach is that by performing
      measurements at different detection angles, the average path length through the
      sample can be varied. For measurements performed on a single sample cell, this
      gives access to a wider range of length and time scales than obtained in a
      conventional DWS setup. Such angle-dependent measurements also offer an important
      consistency check, as for all detection angles the DWS analysis should yield the
      same tracer dynamics, even though the respective path length distributions are
      very different. We validate our approach by performing measurements both on
      aqueous suspensions of tracer particles and on solidlike gelatin samples, for
      which we find our DWS-based microrheology data to be in good agreement with
      rheological measurements performed on the same samples.

PMID- 29347447
TI  - Modeling correlated bursts by the bursty-get-burstier mechanism.
AB  - Temporal correlations of time series or event sequences in natural and social
      phenomena have been characterized by power-law decaying autocorrelation functions
      with decaying exponent gamma. Such temporal correlations can be understood in
      terms of power-law distributed interevent times with exponent alpha and/or
      correlations between interevent times. The latter, often called correlated
      bursts, has recently been studied by measuring power-law distributed bursty
      trains with exponent beta. A scaling relation between alpha and gamma has been
      established for the uncorrelated interevent times, while little is known about
      the effects of correlated interevent times on temporal correlations. In order to
      study these effects, we devise the bursty-get-burstier model for correlated
      bursts, by which one can tune the degree of correlations between interevent
      times, while keeping the same interevent time distribution. We numerically find
      that sufficiently strong correlations between interevent times could violate the
      scaling relation between alpha and gamma for the uncorrelated case. A nontrivial
      dependence of gamma on beta is also found for some range of alpha. The
      implication of our results is discussed in terms of the hierarchical organization
      of bursty trains at various time scales.

PMID- 29347448
TI  - Infinite cascades of phase transitions in the classical Ising chain.
AB  - We report exact results on one of the best studied models in statistical physics:
      the classical antiferromagnetic Ising chain in a magnetic field. We show that the
      model possesses an infinite cascade of thermal phase transitions (also known as
      disorder lines or geometric phase transitions). The phase transition is signaled
      by a change of asymptotic behavior of the nonlocal string-string correlation
      functions when their monotonic decay becomes modulated by incommensurate
      oscillations. The transitions occur for rarefied (m-periodic) strings with
      arbitrary odd m. We propose a duality transformation which maps the Ising chain
      onto the m-leg Ising tube with nearest-neighbor couplings along the legs and the
      plaquette four-spin interactions of adjacent legs. Then the m-string correlation
      functions of the Ising chain are mapped onto the two-point spin-spin correlation
      functions along the legs of the m-leg tube. We trace the origin of these cascades
      of phase transitions to the lines of the Lee-Yang zeros of the Ising chain in m
      periodic complex magnetic field, allowing us to relate these zeros to the
      observable (and potentially measurable) quantities.

PMID- 29347449
TI  - Effective electrostatic interactions in colloid-nanoparticle mixtures.
AB  - Interparticle interactions and bulk properties of colloidal suspensions can be
      substantially modified by the addition of nanoparticles. Extreme asymmetries in
      size and charge between colloidal particles and nanoparticles present severe
      computational challenges to molecular-scale modeling of such complex systems. We
      present a statistical mechanical theory of effective electrostatic interactions
      that can greatly ease large-scale modeling of charged colloid-nanoparticle
      mixtures. By applying a sequential coarse-graining procedure, we show that a
      multicomponent mixture of charged colloids, nanoparticles, counterions, and
      coions can be mapped first onto a binary mixture of colloids and nanoparticles
      and then onto a one-component model of colloids alone. In a linear-response
      approximation, the one-component model is governed by a single effective pair
      potential and a one-body volume energy, whose parameters depend nontrivially on
      nanoparticle size, charge, and concentration. To test the theory, we perform
      molecular dynamics simulations of the two-component and one-component models and
      compute structural properties. For moderate electrostatic couplings, colloid
      colloid radial distribution functions and static structure factors agree closely
      between the two models, validating the sequential coarse-graining approach.
      Nanoparticles of sufficient charge and concentration enhance screening of
      electrostatic interactions, weakening correlations between charged colloids and
      destabilizing suspensions, consistent with experiments.

PMID- 29347450
TI  - Quantum phase transition in an effective three-mode model of interacting bosons.
AB  - In this work we study an effective three-mode model describing interacting
      bosons. These bosons can be considered as exciton-polaritons in a semiconductor
      microcavity at the magic angle. This model exhibits quantum phase transition
      (QPT) when the parameters of the corresponding Hamiltonian are continuously
      varied. The properties of the Hamiltonian spectrum (e.g., the distance between
      two adjacent energy levels) and the phase space structure of the thermodynamic
      limit of the model are used to indicate QPT. The relation between spectral
      properties of the Hamiltonian and the corresponding classical frame of the
      thermodynamic limit of the model is established as indicative of QPT. The average
      number of bosons in a specific mode and the entanglement properties of the ground
      state as functions of the parameters are used to characterize the order of the
      transition and also to construct a phase diagram. Finally, we verify our results
      for experimental data obtained for a setting of exciton-polaritons in a
      semiconductor microcavity.

PMID- 29347451
TI  - Computational investigation of Tb(III) ion line intensities in single-bubble
      sonoluminescence.
AB  - We perform a computational fluid dynamics simulation of trivalent terbium
      [Tb(III)] ion line emissions from single-bubble sonoluminescence (SBSL). Our
      simulation includes dynamic boundary conditions as well as the effects of gas
      properties and quenching by species, such as nitrite ion (NO_{2}^{-}). Simulation
      results demonstrate that when the maximum temperature inside a dimly luminescing
      bubble is relatively low, emission peaks from excited Tb(III) ions are prominent
      within the emission spectra. As the maximum temperature of the bubble increases,
      emission peaks of Tb(III) ions fade away relative to the continuum background
      emission. These calculations match observations of Tb(III) line emissions from
      SBSL occurring in aqueous solutions of terbium nitrate [Tb(NO_{3})_{3}] under an
      argon gas atmosphere. The evolution of the radiation energy spectrum over time
      for sonoluminescing bubbles provides a clear mechanism explaining Tb(III)
      emission peaks gradually merging into the continuous background emission as the
      radiation power increases.

PMID- 29347452
TI  - Incorporating Born solvation energy into the three-dimensional Poisson-Nernst
      Planck model to study ion selectivity in KcsA K^{+} channels.
AB  - Potassium channels are much more permeable to potassium than sodium ions,
      although potassium ions are larger and both carry the same positive charge. This
      puzzle cannot be solved based on the traditional Poisson-Nernst-Planck (PNP)
      theory of electrodiffusion because the PNP model treats all ions as point
      charges, does not incorporate ion size information, and therefore cannot
      discriminate potassium from sodium ions. The PNP model can qualitatively capture
      some macroscopic properties of certain channel systems such as current-voltage
      characteristics, conductance rectification, and inverse membrane potential.
      However, the traditional PNP model is a continuum mean-field model and has no or
      underestimates the discrete ion effects, in particular the ion solvation or self
      energy (which can be described by Born model). It is known that the dehydration
      effect (closely related to ion size) is crucial to selective permeation in
      potassium channels. Therefore, we incorporated Born solvation energy into the PNP
      model to account for ion hydration and dehydration effects when passing through
      inhomogeneous dielectric channel environments. A variational approach was adopted
      to derive a Born-energy-modified PNP (BPNP) model. The model was applied to study
      a cylindrical nanopore and a realistic KcsA channel, and three-dimensional finite
      element simulations were performed. The BPNP model can distinguish different ion
      species by ion radius and predict selectivity for K^{+} over Na^{+} in KcsA
      channels. Furthermore, ion current rectification in the KcsA channel was observed
      by both the PNP and BPNP models. The I-V curve of the BPNP model for the KcsA
      channel indicated an inward rectifier effect for K^{+} (rectification ratio of
      ~3/2) but indicated an outward rectifier effect for Na^{+} (rectification ratio
      of ~1/6).

PMID- 29347453
TI  - Tricriticality in the q-neighbor Ising model on a partially duplex clique.
AB  - We analyze a modified kinetic Ising model, a so-called q-neighbor Ising model,
      with Metropolis dynamics [Phys. Rev. E 92, 052105 (2015)PLEEE81539
      375510.1103/PhysRevE.92.052105] on a duplex clique and a partially duplex clique.
      In the q-neighbor Ising model each spin interacts only with q spins randomly
      chosen from its whole neighborhood. In the case of a duplex clique the change of
      a spin is allowed only if both levels simultaneously induce this change. Due to
      the mean-field-like nature of the model we are able to derive the analytic form
      of transition probabilities and solve the corresponding master equation. The
      existence of the second level changes dramatically the character of the phase
      transition. In the case of the monoplex clique, the q-neighbor Ising model
      exhibits a continuous phase transition for q=3, discontinuous phase transition
      for q>=4, and for q=1 and q=2 the phase transition is not observed. On the other
      hand, in the case of the duplex clique continuous phase transitions are observed
      for all values of q, even for q=1 and q=2. Subsequently we introduce a partially
      duplex clique, parametrized by r?[0,1], which allows us to tune the network from
      monoplex (r=0) to duplex (r=1). Such a generalized topology, in which a fraction
      r of all nodes appear on both levels, allows us to obtain the critical value of
      r=r^{*}(q) at which a tricriticality (switch from continuous to discontinuous
      phase transition) appears.

PMID- 29347454
TI  - Noise-driven neuromorphic tuned amplifier.
AB  - We study a simple stochastic model of neuronal excitatory and inhibitory
      interactions. The model is defined on a directed lattice and internodes couplings
      are modulated by a nonlinear function that mimics the process of synaptic
      activation. We prove that such a system behaves as a fully tunable amplifier: the
      endogenous component of noise, stemming from finite size effects, seeds a
      coherent (exponential) amplification across the chain generating giant
      oscillations with tunable frequencies, a process that the brain could exploit to
      enhance, and eventually encode, different signals. On a wider perspective, the
      characterized amplification process could provide a reliable pacemaking mechanism
      for biological systems. The device extracts energy from the finite size bath and
      operates as an out of equilibrium thermal machine, under stationary conditions.

PMID- 29347455
TI  - Response of jammed packings to thermal fluctuations.
AB  - We focus on the response of mechanically stable (MS) packings of frictionless,
      bidisperse disks to thermal fluctuations, with the aim of quantifying how
      nonlinearities affect system properties at finite temperature. In contrast,
      numerous prior studies characterized the structural and mechanical properties of
      MS packings of frictionless spherical particles at zero temperature. Packings of
      disks with purely repulsive contact interactions possess two main types of
      nonlinearities, one from the form of the interaction potential (e.g., either
      linear or Hertzian spring interactions) and one from the breaking (or forming) of
      interparticle contacts. To identify the temperature regime at which the contact
      breaking nonlinearities begin to contribute, we first calculated the minimum
      temperatures T_{cb} required to break a single contact in the MS packing for both
      single- and multiple-eigenmode perturbations of the T=0 MS packing. We find that
      the temperature required to break a single contact for equal velocity-amplitude
      perturbations involving all eigenmodes approaches the minimum value obtained for
      a perturbation in the direction connecting disk pairs with the smallest overlap.
      We then studied deviations in the constant volume specific heat C[over -]_{V} and
      deviations of the average disk positions Deltar from their T=0 values in the
      temperature regime T_{C[over -]_{V}}<T<T_{r}, where T_{r} is the temperature
      beyond which the system samples the basin of a new MS packing. We find that the
      deviation in the specific heat per particle DeltaC[over -]_{V}^{0}/C[over 
      ]_{V}^{0} relative to the zero-temperature value C[over -]_{V}^{0} can grow
      rapidly above T_{cb}; however, the deviation DeltaC[over -]_{V}^{0}/C[over 
      ]_{V}^{0} decreases as N^{-1} with increasing system size. To characterize the
      relative strength of contact-breaking versus form nonlinearities, we measured the
      ratio of the average position deviations Deltar^{ss}/Deltar^{ds} for single- and
      double-sided linear and nonlinear spring interactions. We find that
      Deltar^{ss}/Deltar^{ds}>100 for linear spring interactions is independent of
      system size. This result emphasizes that contact-breaking nonlinearities are
      dominant over form nonlinearities in the low-temperature range T_{cb}<T<T_{r} for
      model jammed systems.

PMID- 29347456
TI  - Survivability of a metapopulation under local extinctions.
AB  - A metapopulation structure in landscape ecology comprises a group of interacting
      spatially separated subpopulations or patches of the same species that may
      experience several local extinctions. This makes the investigation of
      survivability (in the form of global oscillation) of a metapopulation on top of
      diverse dispersal topologies extremely crucial. However, among various dispersal
      topologies in ecological networks, which one can provide higher metapopulation
      survivability under local extinction is still not well explored. In this article,
      we scrutinize the robustness of an ecological network consisting of prey-predator
      patches having Holling type I functional response, against progressively extinct
      population patches. We present a comprehensive study on this while considering
      global, small-world, and scale-free dispersal of the subpopulations. Furthermore,
      we extend our work in enhancing survivability in the form of sustained global
      oscillation by introducing asymmetries in the dispersal rates of the considered
      species. Our findings affirm that the asynchrony among the patches plays an
      important role in the survivability of a metapopulation. In order to demonstrate
      the model independence of the observed phenomenon, we perform a similar analysis
      for patches exhibiting Holling type II functional response. On the grounds of the
      obtained results, our work is expected to provide a better perception of the
      influence of dispersal arrangements on the global survivability of ecological
      networks.

PMID- 29347457
TI  - Pinning and unbinding of ideal polymers from a wedge corner.
AB  - A polymer repelled by unfavorable interactions with a uniform flat surface may
      still be pinned to attractive edges and corners. This is demonstrated by
      considering adsorption of a two-dimensional ideal polymer to an attractive corner
      of a repulsive wedge. The well-known mapping between the statistical mechanics of
      an ideal polymer and the quantum problem of a particle in a potential is then
      used to analyze the singular behavior of the unbinding transition of the polymer.
      The divergence of the localization length is found to be governed by an exponent
      that varies continuously with the angle (when reflex). Numerical treatment of the
      discrete (lattice) version of such an adsorption problem confirms this behavior.

PMID- 29347458
TI  - Emergent dynamic structures and statistical law in spherical lattice gas
      automata.
AB  - Various lattice gas automata have been proposed in the past decades to simulate
      physics and address a host of problems on collective dynamics arising in diverse
      fields. In this work, we employ the lattice gas model defined on the sphere to
      investigate the curvature-driven dynamic structures and analyze the statistical
      behaviors in equilibrium. Under the simple propagation and collision rules, we
      show that the uniform collective movement of the particles on the sphere is
      geometrically frustrated, leading to several nonequilibrium dynamic structures
      not found in the planar lattice, such as the emergent bubble and vortex
      structures. With the accumulation of the collision effect, the system ultimately
      reaches equilibrium in the sense that the distribution of the coarse-grained
      speed approaches the two-dimensional Maxwell-Boltzmann distribution despite the
      population fluctuations in the coarse-grained cells. The emergent regularity in
      the statistical behavior of the system is rationalized by mapping our system to a
      generalized random walk model. This work demonstrates the capability of the
      spherical lattice gas automaton in revealing the lattice-guided dynamic
      structures and simulating the equilibrium physics. It suggests the promising
      possibility of using lattice gas automata defined on various curved surfaces to
      explore geometrically driven nonequilibrium physics.

PMID- 29347459
TI  - Acoustic manipulation: Bessel beams and active carriers.
AB  - In this paper, we address the interaction of zero-order acoustic Bessel beams as
      an acoustic manipulation tool, with an active spherical shell, as a carrier in
      drug, agent, or material delivery systems, in order to investigate the
      controllability of exerted acoustic radiation force as the driver. The active
      body is comprised of a spherical elastic shell stimulated in its monopole mode of
      vibrations with the same frequency as the incident wave field via an internally
      bonded and spatially uniformly excited piezoelectric actuator. The main aim of
      this work is to examine the performance of a nondiffracting and self
      reconstructing zero-order Bessel beam to obtain the full manipulability condition
      of active carriers in comparison with the case of a plane wave field. The results
      unveil some unique potentials of the Bessel beams in the company of active
      carriers, with emphasis on the consumed power of the actuation system. This paper
      will widen the path toward the single-beam robust acoustic manipulation
      techniques and may lead to the prospect of combined tweezers and fields, with
      applications in delivery systems, microswimmers, and trapper designs.

PMID- 29347460
TI  - Boltzmann kinetic equation for a strongly confined gas of hard spheres.
AB  - A Boltzmann-like kinetic equation for a quasi-two-dimensional gas of hard spheres
      is derived. The system is confined between two parallel hard plates separated a
      distance between one and two particle diameters. An entropy Lyapunov function for
      the equation is identified. In addition to the usual Boltzmann expression, it
      contains a contribution associated to the confinement of the particles. The
      steady properties of the system agree with equilibrium statistical mechanics
      results. Equations describing the energy transfer between the degrees of freedom
      parallel and perpendicular to the confining plates are obtained for some simple
      initial configurations. The theoretical predictions are compared with molecular
      dynamics simulation data and a good agreement is found.

PMID- 29347461
TI  - Strongly nonlinear theory of rapid solidification near absolute stability.
AB  - We investigate the nonlinear evolution of the morphological deformation of a
      solid-liquid interface of a binary melt under rapid solidification conditions
      near two absolute stability limits. The first of these involves the complete
      stabilization of the system to cellular instabilities as a result of large enough
      surface energy. We derive nonlinear evolution equations in several limits in this
      scenario and investigate the effect of interfacial disequilibrium on the
      nonlinear deformations that arise. In contrast to the morphological stability
      problem in equilibrium, in which only cellular instabilities appear and only one
      absolute stability boundary exists, in disequilibrium the system is prone to
      oscillatory instabilities and a second absolute stability boundary involving
      attachment kinetics arises. Large enough attachment kinetics stabilize the
      oscillatory instabilities. We derive a nonlinear evolution equation to describe
      the nonlinear development of the solid-liquid interface near this oscillatory
      absolute stability limit. We find that strong asymmetries develop with time. For
      uniform oscillations, the evolution equation for the interface reduces to the
      simple form f^{''}+(betaf^{'})^{2}+f=0, where beta is the disequilibrium
      parameter. Lastly, we investigate a distinguished limit near both absolute
      stability limits in which the system is prone to both cellular and oscillatory
      instabilities and derive a nonlinear evolution equation that captures the
      nonlinear deformations in this limit. Common to all these scenarios is the
      emergence of larger asymmetries in the resulting shapes of the solid-liquid
      interface with greater departures from equilibrium and larger morphological
      numbers. The disturbances additionally sharpen near the oscillatory absolute
      stability boundary, where the interface becomes deep-rooted. The oscillations are
      time-periodic only for small-enough initial amplitudes and their frequency
      depends on a single combination of physical parameters, including the
      morphological number, as well as the amplitude. The critical amplitude, at which
      solutions loose periodicity, depends on a single combination of parameters
      independent of the morphological number that indicate that non-periodic growth is
      most commonly present for moderate disequilibrium parameters. The spatial
      distribution of the interface develops deepening roots at late times. Similar
      spatial distributions are also seen in the limit in which both the cellular and
      oscillatory modes are close to absolute stability, and the roots deepen with
      larger departures from the two absolute stability boundaries.

PMID- 29347462
TI  - Underdamped stochastic harmonic oscillator driven by Levy noise.
AB  - We investigate the distribution of potential and kinetic energy in stationary
      states of the linearly damped stochastic oscillator driven by Levy noises. In the
      long time limit distributions of kinetic and potential energies of the oscillator
      follow the power-law asymptotics and do not fulfill the equipartition theorem.
      The partition of the mechanical energy is controlled by the damping coefficient.
      In the limit of vanishing damping a stochastic analog of the equipartition
      theorem can be proposed, namely, the statistical properties of potential and
      kinetic energies attain distributions characterized by the same widths. For
      larger damping coefficient the larger fraction of energy is stored in its
      potential form. In the limit of very strong damping the contribution of kinetic
      energy becomes negligible. Finally, we demonstrate that the ratio of
      instantaneous kinetic and potential energies, which signifies departure from the
      mechanical energy equipartition, follows universal power-law asymptotics,
      regardless of the symmetric alpha-stable noise parameters. Altogether our
      investigations clearly indicate strongly nonequilibrium character of Levy-stable
      fluctuations with the stability index alpha<2.

PMID- 29347463
TI  - Random Euclidean matching problems in one dimension.
AB  - We discuss the optimal matching solution for both the assignment problem and the
      matching problem in one dimension for a large class of convex cost functions. We
      consider the problem in a compact set with the topology both of the interval and
      of the circumference. Afterwards, we assume the points' positions to be random
      variables identically and independently distributed on the considered domain. We
      analytically obtain the average optimal cost in the asymptotic regime of very
      large number of points N and some correlation functions for a power-law-type cost
      function in the form c(z)=z^{p}, both in the p>1 case and in the p<0 case. The
      scaling of the optimal mean cost with the number of points is N^{-p/2} for the
      assignment and N^{-p} for the matching when p>1, whereas in both cases it is a
      constant when p<0. Finally, our predictions are compared with the results of
      numerical simulations.

PMID- 29347464
TI  - Erosion and deposition processes in surface granular flows.
AB  - We report on experiments aiming at characterizing erosion and deposition
      processes on a tilted granular bed. We investigate the existence of the neutral
      angle, that is, the critical angle at which erosion exactly balances accretion
      after the passage of a granular avalanche of a finite mass. Experiments show in
      particular that the neutral angle depends on both avalanche mass and shape but is
      rather insensitive to the bed length. This result strongly suggests that the
      effective friction between the static and mobile granular phases cannot be taken
      as an intrinsic property that is only material dependent but should be considered
      a flow-dependent property. Interestingly, for a given avalanche mass, the net
      erosion rate increases linearly with the angular deviation from the neutral
      angle. We also compare our data with the predictions of the erosion-deposition
      model introduced by Bouchaud, Cates, Ravi Prakash, and Edwards (BCRE) [J. Phys. I
      4, 1283 (1994)JPGCE81155-430410.1051/jp1:1994195]. We show that the predictions
      drawn from the modified version of the BCRE model proposed by Boutreux and de
      Gennes, in which the local erosion rate between the static and mobile phases is
      independent of the flow thickness, are in remarkable agreement with the
      experimental results.

PMID- 29347465
TI  - Roles of energy eigenstates and eigenvalues in equilibration of isolated quantum
      systems.
AB  - We show that eigenenergies and energy eigenstates play different roles in the
      equilibration process of an isolated quantum system. Their roles are revealed
      numerically by exchanging the eigenenergies between an integrable model and a
      nonintegrable model. We find that the structure of eigenenergies of a
      nonintegrable model characterized by nondegeneracy ensures that quantum revival
      occurs rarely whereas the energy eigenstates of a nonintegrable model suppress
      the fluctuations for the equilibrated quantum state. Our study is aided with a
      quantum entropy that describes how randomly a wave function is distributed in
      quantum phase space. We also demonstrate with this quantum entropy the validity
      of Berry's conjecture for energy eigenstates. This implies that the energy
      eigenstates of a nonintegrable model appear indeed random.

PMID- 29347466
TI  - Intermittency and emergence of coherent structures in wave turbulence of a
      vibrating plate.
AB  - We report numerical investigations of wave turbulence in a vibrating plate. The
      possibility to implement advanced measurement techniques and long-time numerical
      simulations makes this system extremely valuable for wave turbulence studies. The
      purely 2D character of dynamics of the elastic plate makes it much simpler to
      handle compared to much more complex 3D physical systems that are typical of geo-
      and astrophysical issues (ocean surface or internal waves, magnetized plasmas or
      strongly rotating and/or stratified flows). When the forcing is small the
      observed wave turbulence is consistent with the predictions of the weak turbulent
      theory. Here we focus on the case of stronger forcing for which coherent
      structures can be observed. These structures look similar to the folds and D
      cones that are commonly observed for strongly deformed static thin elastic sheets
      (crumpled paper) except that they evolve dynamically in our forced system. We
      describe their evolution and show that their emergence is associated with
      statistical intermittency (lack of self similarity) of strongly nonlinear wave
      turbulence. This behavior is reminiscent of intermittency in Navier-Stokes
      turbulence. Experimental data show hints of the weak to strong turbulence
      transition. However, due to technical limitations and dissipation, the strong
      nonlinear regime remains out of reach of experiments and therefore has been
      explored numerically.

PMID- 29347467
TI  - Increased persistence via asynchrony in oscillating ecological populations with
      long-range interaction.
AB  - Understanding the influence of the structure of a dispersal network on the
      species persistence and modeling a realistic species dispersal in nature are two
      central issues in spatial ecology. A realistic dispersal structure which favors
      the persistence of interacting ecological systems was studied [M. D. Holland and
      A. Hastings, Nature (London) 456, 792 (2008)NATUAS0028-083610.1038/nature07395],
      where it was shown that a randomization of the structure of a dispersal network
      in a metapopulation model of prey and predator increases the species persistence
      via clustering, prolonged transient dynamics, and amplitudes of population
      fluctuations. In this paper, by contrast, we show that a deterministic network
      topology in a metapopulation can also favor asynchrony and prolonged transient
      dynamics if species dispersal obeys a long-range interaction governed by a
      distance-dependent power law. To explore the effects of power-law coupling, we
      take a realistic ecological model, namely, the Rosenzweig-MacArthur model in each
      patch (node) of the network of oscillators, and show that the coupled system is
      driven from synchrony to asynchrony with an increase in the power-law exponent.
      Moreover, to understand the relationship between species persistence and
      variations in power-law exponent, we compute a correlation coefficient to
      characterize cluster formation, a synchrony order parameter, and median predator
      amplitude. We further show that smaller metapopulations with fewer patches are
      more vulnerable to extinction as compared to larger metapopulations with a higher
      number of patches. We believe that the present work improves our understanding of
      the interconnection between the random network and the deterministic network in
      theoretical ecology.

PMID- 29347468
TI  - Hypernetted-chain-like closure of Ornstein-Zernike equation in multibody
      dissipative particle dynamics.
AB  - We have derived a hypernetted-chain-like (HNC-like) approximate closure of the
      Ornstein-Zernike equation for multibody dissipative particle dynamics (MDPD)
      system in which the classic closures are not directly practicable. We first point
      out that the Percus's method is applicable to MDPD system in which particles
      interact with a density-dependent potential. And then an HNC-like closure is
      derived using Percus's idea and the saddle-point approximation of particle free
      energy. This HNC-like closure is compared with results of previous researchers,
      and in many cases, it demonstrates better agreement with computer simulation
      results. The HNC-like closure is used to predict the cluster crystallization in
      MDPD. We determine whether the cluster crystallization will happen in a system
      utilizing the widely applicable Hansen-Verlet freezing criterion and by observing
      the radial distribution function. The conclusions drawn from the results of the
      HNC-like closure are in agreement with computer simulation results. We evaluate
      different weight functions to determine whether they are prone to cluster
      crystallization. A new effective density-dependent pairwise potential is also
      proposed to help to explain the tendency to cluster crystallization of MDPD
      systems.

PMID- 29347469
TI  - Quantum adiabatic protocols using emergent local Hamiltonians.
AB  - We present two applications of emergent local Hamiltonians to speed up quantum
      adiabatic protocols for isolated noninteracting and weakly interacting fermionic
      systems in one-dimensional lattices. We demonstrate how to extract maximal work
      from initial band-insulating states, and how to adiabatically transfer systems
      from linear and harmonic traps into box traps. Our protocols consist of two
      stages. The first one involves a free expansion followed by a quench to an
      emergent local Hamiltonian. In the second stage, the emergent local Hamiltonian
      is "turned off" quasistatically. For the adiabatic transfer from a harmonic trap,
      we consider both zero- and nonzero-temperature initial states.

PMID- 29347470
TI  - Microstructure as a function of the grain size distribution for packings of
      frictionless disks: Effects of the size span and the shape of the distribution.
AB  - This article presents a numerical study of the effects of grain size distribution
      (GSD) on the microstructure of two-dimensional packings of frictionless disks.
      The GSD is described by a power law with two parameters controlling the size span
      and the shape of the distribution. First, several samples are built for each
      combination of these parameters. Then, by means of contact dynamics simulations,
      the samples are densified in oedometric conditions and sheared in a simple shear
      configuration. The microstructure is analyzed in terms of packing fraction, local
      ordering, connectivity, and force transmission properties. It is shown that the
      microstructure is notoriously affected by both the size span and the shape of the
      GSD. These findings confirm recent observations regarding the size span of the
      GSD and extend previous works by describing the effects of the GSD shape.
      Specifically, we find that if the GSD shape is varied by increasing the
      proportion of small grains by a certain amount, it is possible to increase the
      packing fraction, increase coordination, and decrease the proportion of floating
      particles. Thus, by carefully controlling the GSD shape, it is possible to obtain
      systems that are denser and better connected, probably increasing the system's
      robustness and optimizing important strength properties such as stiffness,
      cohesion, and fragmentation susceptibility.

PMID- 29347471
TI  - Linear-shear-current modified Schrodinger equation for gravity waves in finite
      water depth.
AB  - A nonlinear Schrodinger equation for the propagation of two-dimensional surface
      gravity waves on linear shear currents in finite water depth is derived. In the
      derivation, linear shear currents are assumed to be a linear combination of depth
      uniform currents and constant vorticity. Therefore, the equation includes the
      combined effects of depth-uniform currents and constant vorticity. Next, using
      the equation, the properties of the modulational instability of gravity waves on
      linear shear currents are investigated. It is showed that shear currents
      significantly modify the modulational instability properties of weakly nonlinear
      waves. Furthermore, the influence of linear shear currents on Peregrine breather
      which can be seen as a prototype of freak waves is also studied. It is
      demonstrated that depth-uniform opposing currents can reduce the breather
      extension in both the time and spatial domain in intermediate water depth, but
      following currents has the adverse impact, indicating that a wave packets with
      freak waves formed on following currents contain more hazardous waves in finite
      water depth. However, the corresponding and coexisting vorticity can counteract
      the influence of currents. Additionally, if the water depth is deep enough, shear
      currents have negligible effect on the characteristics of Peregrine breathers.

PMID- 29347472
TI  - Extinction dynamics from metastable coexistences in an evolutionary game.
AB  - Deterministic evolutionary game dynamics can lead to stable coexistences of
      different types. Stochasticity, however, drives the loss of such coexistences.
      This extinction is usually accompanied by population size fluctuations. We
      investigate the most probable extinction trajectory under such fluctuations by
      mapping a stochastic evolutionary model to a problem of classical mechanics using
      the Wentzel-Kramers-Brillouin (WKB) approximation. Our results show that more
      abundant types in a coexistence may be more likely to go extinct first, in good
      agreement with previous results. The distance between the coexistence and
      extinction points is not a good predictor of extinction either. Instead, the WKB
      method correctly predicts the type going extinct first.

PMID- 29347473
TI  - Visual evaluation of surface anchoring strength by electrohydrodynamic convection
      of a nematic liquid crystal.
AB  - Visual evaluation of the surface anchoring energies in a nematic liquid crystal
      (LC) cell is characterized by the direction of the convection roll pattern that
      appears in the low-frequency conduction regime. The convection roll pattern in a
      twisted nematic LC (TNLC) cell is oriented perpendicular to the midplane LC
      director dominating the direction of convection flow, and its direction is
      determined by the relative surface anchoring energy between two surface
      boundaries. Thus the direction of the roll pattern generated at the TNLC cell
      with asymmetric LC alignment layers can provide information on the surface
      anchoring energies at the two boundaries. We demonstrate a method for determining
      the two anchoring energies through a measured midplane LC director applied to the
      Ericksen-Leslie equation.

PMID- 29347474
TI  - Space-time-modulated stochastic processes.
AB  - Starting from the physical problem associated with the Lorentzian transformation
      of a Poisson-Kac process in inertial frames, the concept of space-time-modulated
      stochastic processes is introduced for processes possessing finite propagation
      velocity. This class of stochastic processes provides a two-way coupling between
      the stochastic perturbation acting on a physical observable and the evolution of
      the physical observable itself, which in turn influences the statistical
      properties of the stochastic perturbation during its evolution. The definition of
      space-time-modulated processes requires the introduction of two functions: a
      nonlinear amplitude modulation, controlling the intensity of the stochastic
      perturbation, and a time-horizon function, which modulates its statistical
      properties, providing irreducible feedback between the stochastic perturbation
      and the physical observable influenced by it. The latter property is the peculiar
      fingerprint of this class of models that makes them suitable for extension to
      generic curved-space times. Considering Poisson-Kac processes as prototypical
      examples of stochastic processes possessing finite propagation velocity, the
      balance equations for the probability density functions associated with their
      space-time modulations are derived. Several examples highlighting the
      peculiarities of space-time-modulated processes are thoroughly analyzed.

PMID- 29347475
TI  - Micromechanical model for protein materials: From macromolecules to macroscopic
      fibers.
AB  - We propose a model for the mechanical behavior of protein materials. Based on a
      limited number of experimental macromolecular parameters (persistence and contour
      length) we obtain the macroscopic behavior of keratin fibers (human, cow, and
      rabbit hair), taking into account the damage and residual stretches effects that
      are fundamental in many functions of life. We also show the capability of our
      approach to describe the main dissipation and permanent strain effects observed
      in the more complex spider silk fibers. The comparison between our results and
      the data obtained experimentally from cyclic tests demonstrates that our model is
      robust and is able to reproduce with a remarkable accuracy the experimental
      behavior of all protein materials we tested.

PMID- 29347476
TI  - Avoided level crossings in an elliptic billiard.
AB  - In an elliptic billiard, we find avoided level crossings taking place over wide
      ranges, which are of a Demkov type for generations of eigenfunctions localized on
      an islands chain and its pair unstable periodic orbit. For a proof of the
      existence of avoided level crossings, first, we show that the quantized
      eigenvalue of the unstable periodic orbit, obtained by the Einstein-Brillouin
      Keller quantization rule, passes the eigenvalues of bouncing-ball modes localized
      on the unstable periodic orbit after Demkov type avoided level crossings so that
      pairs of bouncing-ball modes are sequentially generated. Next, by using a
      perturbed Hamiltonian, we show that off-diagonal elements in Hamiltonian are
      nonzero, which give rise to an interaction between two eigenfunctions. Last, we
      verify that the observed phenomenon is Fermi resonance: that is, the quantum
      number difference of two normal modes equals the periodic orbits, where
      eigenfunctions are localized after an avoided level crossing.

PMID- 29347477
TI  - Early warning signal for interior crises in excitable systems.
AB  - The ability to reliably predict critical transitions in dynamical systems is a
      long-standing goal of diverse scientific communities. Previous work focused on
      early warning signals related to local bifurcations (critical slowing down) and
      nonbifurcation-type transitions. We extend this toolbox and report on a
      characteristic scaling behavior (critical attractor growth) which is indicative
      of an impending global bifurcation, an interior crisis in excitable systems. We
      demonstrate our early warning signal in a conceptual climate model as well as in
      a model of coupled neurons known to exhibit extreme events. We observed critical
      attractor growth prior to interior crises of chaotic as well as strange
      nonchaotic attractors. These observations promise to extend the classes of
      transitions that can be predicted via early warning signals.

PMID- 29347478
TI  - Chaotic behavior in Casimir oscillators: A case study for phase-change materials.
AB  - Casimir forces between material surfaces at close proximity of less than 200 nm
      can lead to increased chaotic behavior of actuating devices depending on the
      strength of the Casimir interaction. We investigate these phenomena for phase
      change materials in torsional oscillators, where the amorphous to crystalline
      phase transitions lead to transitions between high and low Casimir force and
      torque states, respectively, without material compositions. For a conservative
      system bifurcation curve and Poincare maps analysis show the absence of chaotic
      behavior but with the crystalline phase (high force-torque state) favoring more
      unstable behavior and stiction. However, for a nonconservative system chaotic
      behavior can take place introducing significant risk for stiction, which is again
      more pronounced for the crystalline phase. The latter illustrates the more
      general scenario that stronger Casimir forces and torques increase the
      possibility for chaotic behavior. The latter is making it impossible to predict
      whether stiction or stable actuation will occur on a long-term basis, and it is
      setting limitations in the design of micronano devices operating at short-range
      nanoscale separations.

PMID- 29347479
TI  - Strength distribution of large unidirectional composite patches with realistic
      load sharing.
AB  - Monte Carlo simulations of the failure of unidirectional fiber composites in a
      plane transverse to the fiber direction are performed on much larger patches than
      in previous works, assuming a realistic load redistribution scheme from broken to
      intact fibers. Computational effort involved in these simulations is
      substantially reduced using an algorithm based on the quadtree data structure.
      The empirical strength distribution obtained from the simulations has a weak-link
      character, regardless of the variability in fiber strengths. The empirical
      strength distribution is well captured by a probabilistic model based on the
      growth of a tight cluster of fiber breaks. It is also well captured by regarding
      composite patch failure as the failure of the weakest equal load-sharing bundle
      of a certain size, following Curtin [Phys. Rev. Lett. 80, 1445 (1998)PRLTAO0031
      900710.1103/PhysRevLett.80.1445]. The approximate coincidence of these two
      predictions identifies the dominant failure mechanism underlying Curtin's
      empirical scaling relationship.

PMID- 29347480
TI  - Effect of mobility ratio on interaction between the fingers in unstable growth
      processes.
AB  - We investigate interactions between thin fingers formed as a result of an
      instability of an advancing front in growth processes. We show that the fingers
      can both attract and repel each other, depending on their lengths and the
      mobility ratio between the invading and displaced phase. To understand the origin
      of these interactions we introduce a simple resistor model of the fingers. The
      predictions of the model are then compared to the numerical simulations of two
      unstable growth processes: dissolution of partially cemented rock fracture and
      viscous fingering in a regular network of channels.

PMID- 29347481
TI  - Effective optimization using sample persistence: A case study on quantum
      annealers and various Monte Carlo optimization methods.
AB  - We present and apply a general-purpose, multistart algorithm for improving the
      performance of low-energy samplers used for solving optimization problems. The
      algorithm iteratively fixes the value of a large portion of the variables to
      values that have a high probability of being optimal. The resulting problems are
      smaller and less connected, and samplers tend to give better low-energy samples
      for these problems. The algorithm is trivially parallelizable since each start in
      the multistart algorithm is independent, and could be applied to any heuristic
      solver that can be run multiple times to give a sample. We present results for
      several classes of hard problems solved using simulated annealing, path-integral
      quantum Monte Carlo, parallel tempering with isoenergetic cluster moves, and a
      quantum annealer, and show that the success metrics and the scaling are improved
      substantially. When combined with this algorithm, the quantum annealer's scaling
      was substantially improved for native Chimera graph problems. In addition, with
      this algorithm the scaling of the time to solution of the quantum annealer is
      comparable to the Hamze-de Freitas-Selby algorithm on the weak-strong cluster
      problems introduced by Boixo et al. Parallel tempering with isoenergetic cluster
      moves was able to consistently solve three-dimensional spin glass problems with
      8000 variables when combined with our method, whereas without our method it could
      not solve any.

PMID- 29347482
TI  - Evolutionary games combining two or three pair coordinations on a square lattice.
AB  - We study multiagent logit-rule-driven evolutionary games on a square lattice
      whose pair interactions are composed of a maximal number of nonoverlapping
      elementary coordination games describing Ising-type interactions between just two
      of the available strategies. Using Monte Carlo simulations we investigate the
      macroscopic noise-level-dependent behavior of the two- and three-pair games and
      the critical properties of the continuous phase transtitions these systems
      exhibit. The four-strategy game is shown to be equivalent to a system that
      consists of two independent and identical Ising models.

PMID- 29347483
TI  - Quantum fidelity approach to the ground-state properties of the one-dimensional
      axial next-nearest-neighbor Ising model in a transverse field.
AB  - In this work we analyze the ground-state properties of the s=1/2 one-dimensional
      axial next-nearest-neighbor Ising model in a transverse field using the quantum
      fidelity approach. We numerically determined the fidelity susceptibility as a
      function of the transverse field B_{x} and the strength of the next-nearest
      neighbor interaction J_{2}, for systems of up to 24 spins. We also examine the
      ground-state vector with respect to the spatial ordering of the spins. The ground
      state phase diagram shows ferromagnetic, floating, and <2,2> phases, and we
      predict an infinite number of modulated phases in the thermodynamic limit (L
      >infinity). Paramagnetism only occurs for larger magnetic fields. The transition
      lines separating the modulated phases seem to be of second order, whereas the
      line between the floating and the <2,2> phases is possibly of first order.

PMID- 29347484
TI  - Partial inertia induces additional phase transition in the majority vote model.
AB  - Explosive (i.e., discontinuous) transitions have aroused great interest by
      manifesting in distinct systems, such as synchronization in coupled oscillators,
      percolation regime, absorbing phase transitions, and more recently, the majority
      vote model with inertia. In the latter, the model rules are slightly modified by
      the inclusion of a term depending on the local spin (an inertial term). In such a
      case, Chen et al. [Phys Rev. E 95, 042304 (2017)2470
      004510.1103/PhysRevE.95.042304] have found that relevant inertia changes the
      nature of the phase transition in complex networks, from continuous to
      discontinuous. Here we give a further step by embedding inertia only in vertices
      with degree larger than a threshold value <k>k^{*}, <k> being the mean system
      degree and k^{*} the fraction restriction. Our results, from mean-field analysis
      and extensive numerical simulations, reveal that an explosive transition is
      presented in both homogeneous and heterogeneous structures for small and
      intermediate k^{*}'s. Otherwise, a large restriction can sustain a discontinuous
      transition only in the heterogeneous case. This shares some similarities with
      recent results for the Kuramoto model [Phys. Rev. E 91, 022818 (2015)PLEEE81539
      375510.1103/PhysRevE.91.022818]. Surprisingly, intermediate restriction and large
      inertia are responsible for the emergence of an extra phase, in which the system
      is partially synchronized and the classification of phase transition depends on
      the inertia and the lattice topology. In this case, the system exhibits two phase
      transitions.

PMID- 29347485
TI  - Mixing and transport from combined stretching-and-folding and cutting-and
      shuffling.
AB  - While structures and bifurcations controlling tracer particle transport and
      mixing have been studied extensively for systems with only stretching-and
      folding, and to a lesser extent for systems with only cutting-and-shuffling, few
      studies have considered systems with a combination of both. We demonstrate two
      bifurcations for nonmixing islands associated with elliptic periodic points that
      only occur in systems with combined cutting-and-shuffling and stretching-and
      folding, using as an example a map approximating biaxial rotation of a less-than
      half-full spherical granular tumbler. First, we characterize a bifurcation of
      elliptic island containment, from containment by manifolds associated with
      hyperbolic periodic points to containment by cutting line tangency. As a result,
      the maximum size of the nonmixing region occurs when the island is at the
      bifurcation point. We also demonstrate a bifurcation where periodic points are
      annihilated by the cutting-and-shuffling action. Chains of elliptic and
      hyperbolic periodic points that arise when invariant tori surrounding an elliptic
      point break up [according to Kolmogorov-Arnold-Moser (KAM) theory] can annihilate
      when they meet a cutting line. Consequently, the Poincare index (a topological
      invariant of smooth systems) is not preserved.

PMID- 29347486
TI  - Electrostatic double-layer interaction between stacked charged bilayers.
AB  - The inapplicability of the DLVO theory to multilayered anionic bilayers is found
      in terms of the co-ion-valence dependence of the lamellar repeat distance. Most
      of the added salt is expelled from the interlamellar space to the bulk due to the
      Gibbs-Donnan effect on multiple bilayers with the bulk. The electrostatic double
      layer interaction is well expressed by the formula recently proposed by Trefalt.
      The osmotic pressure due to the expelled ions, rather than the van der Waals
      interaction, is the main origin of the attractive force between the bilayers.

PMID- 29347487
TI  - Nonstationary Markovian replication process causing diverse diffusions.
AB  - We introduce a single generative mechanism that can be used to describe diverse
      nonstationary diffusions. A nonstationary Markovian replication process for steps
      is considered for which we derive analytically the time evolution of the
      probability distribution of the walker's displacement and the generalized
      telegrapher equation with time-varying coefficients, and we find that diffusivity
      can be determined by temporal changes of replication of an immediate step. By
      controlling the replications, we realize diverse diffusions such as alternating
      diffusion, superdiffusion, subdiffusion, and marginal diffusion, which originate
      from oscillating, increasing, decreasing, and slowly increasing or decreasing
      replications with time, respectively.

PMID- 29347488
TI  - Numerical calculation on a two-step subdiffusion behavior of lateral protein
      movement in plasma membranes.
AB  - A two-step subdiffusion behavior of lateral movement of transmembrane proteins in
      plasma membranes has been observed by using single-molecule experiments. A nested
      double-compartment model where large compartments are divided into several
      smaller ones has been proposed in order to explain this observation. These
      compartments are considered to be delimited by membrane-skeleton "fences" and
      membrane-protein "pickets" bound to the fences. We perform numerical simulations
      of a master equation using a simple two-dimensional lattice model to investigate
      the heterogeneous diffusion dynamics behavior of transmembrane proteins within
      plasma membranes. We show that the experimentally observed two-step subdiffusion
      process can be described using fence and picket models combined with decreased
      local diffusivity of transmembrane proteins in the vicinity of the pickets. This
      allows us to explain the two-step subdiffusion behavior without explicitly
      introducing nested double compartments.

PMID- 29347489
TI  - Entropy of level-cut random Gaussian structures at different volume fractions.
AB  - Cutting random Gaussian fields at a given level can create a variety of
      morphologically different two- or several-phase structures that have often been
      used to describe physical systems. The entropy of such structures depends on the
      covariance function of the generating Gaussian random field, which in turn
      depends on its spectral density. But the entropy of level-cut structures also
      depends on the volume fractions of different phases, which is determined by the
      selection of the cutting level. This dependence has been neglected in earlier
      work. We evaluate the entropy of several lattice models to show that, even in the
      cases of strongly coupled systems, the dependence of the entropy of level-cut
      structures on molar fractions of the constituents scales with the simple ideal
      noninteracting system formula. In the last section, we discuss the application of
      the results to binary or ternary fluids and microemulsions.

PMID- 29347490
TI  - Free-energy barriers for crystal nucleation from fluid phases.
AB  - Monte Carlo simulations of crystal nuclei coexisting with the fluid phase in
      thermal equilibrium in finite volumes are presented and analyzed, for fluid
      densities from dense melts to the vapor. Generalizing the lever rule for two
      phase coexistence in the canonical ensemble to finite volume, "measurements" of
      the nucleus volume together with the pressure and chemical potential of the
      surrounding fluid allows us to extract the surface free energy of the nucleus.
      Neither the knowledge of the (in general nonspherical) nucleus shape nor of the
      angle-dependent interface tension is required for this task. The feasibility of
      the approach is demonstrated for a variant of the Asakura-Oosawa model for
      colloid-polymer mixtures, which form face-centered cubic colloidal crystals. For
      a polymer to colloid size ratio of 0.15, the colloid packing fraction in the
      fluid phase can be varied from melt values to zero by the variation of an
      effective attractive potential between the colloids. It is found that the
      approximation of spherical crystal nuclei often underestimates actual nucleation
      barriers significantly. Nucleation barriers are found to scale as
      DeltaF^{*}=(4pi/3)^{1/3}gamma[over -](V^{*})^{2/3}+const with the nucleus volume
      V^{*}, and the effective surface tension gamma[over -] that accounts implicitly
      for the nonspherical shape can be precisely estimated.

PMID- 29347491
TI  - Broadening of cyclotron resonance conditions in the relativistic interaction of
      an intense laser with overdense plasmas.
AB  - The interaction of dense plasmas with an intense laser under a strong external
      magnetic field has been investigated. When the cyclotron frequency for the
      ambient magnetic field is higher than the laser frequency, the laser's
      electromagnetic field is converted to the whistler mode that propagates along the
      field line. Because of the nature of the whistler wave, the laser light
      penetrates into dense plasmas with no cutoff density, and produces superthermal
      electrons through cyclotron resonance. It is found that the cyclotron resonance
      absorption occurs effectively under the broadened conditions, or a wider range of
      the external field, which is caused by the presence of relativistic electrons
      accelerated by the laser field. The upper limit of the ambient field for the
      resonance increases in proportion to the square root of the relativistic laser
      intensity. The propagation of a large-amplitude whistler wave could raise the
      possibility for plasma heating and particle acceleration deep inside dense
      plasmas.

PMID- 29347492
TI  - Elucidating fluctuating diffusivity in center-of-mass motion of polymer models
      with time-averaged mean-square-displacement tensor.
AB  - There have been increasing reports that the diffusion coefficient of
      macromolecules depends on time and fluctuates randomly. Here a method is
      developed to elucidate this fluctuating diffusivity from trajectory data. Time
      averaged mean-square displacement (MSD), a common tool in single-particle
      tracking (SPT) experiments, is generalized to a second-order tensor with which
      both magnitude and orientation fluctuations of the diffusivity can be clearly
      detected. This method is used to analyze the center-of-mass motion of four
      fundamental polymer models: the Rouse model, the Zimm model, a reptation model,
      and a rigid rodlike polymer. It is found that these models exhibit distinctly
      different types of magnitude and orientation fluctuations of diffusivity. This is
      an advantage of the present method over previous ones, such as the ergodicity
      breaking parameter and a non-Gaussian parameter, because with either of these
      parameters it is difficult to distinguish the dynamics of the four polymer
      models. Also, the present method of a time-averaged MSD tensor could be used to
      analyze trajectory data obtained in SPT experiments.

PMID- 29347493
TI  - Kinetic theory of shear thickening for a moderately dense gas-solid suspension:
      From discontinuous thickening to continuous thickening.
AB  - The Enskog kinetic theory for moderately dense gas-solid suspensions under simple
      shear flow is considered as a model to analyze the rheological properties of the
      system. The influence of the environmental fluid on solid particles is modeled
      via a viscous drag force plus a stochastic Langevin-like term. The Enskog
      equation is solved by means of two independent but complementary routes: (i)
      Grad's moment method and (ii) event-driven Langevin simulation of hard spheres.
      Both approaches clearly show that the flow curve (stress-strain rate relation)
      depends significantly on the volume fraction of the solid particles. In
      particular, as the density increases, there is a transition from the
      discontinuous shear thickening (observed in dilute gases) to the continuous shear
      thickening for denser systems. The comparison between theory and simulations
      indicates that while the theoretical predictions for the kinetic temperature
      agree well with simulations for densities phi?0.5, the agreement for the other
      rheological quantities (the viscosity, the stress ratio, and the normal stress
      differences) is limited to more moderate densities (phi?0.3) if the inelasticity
      during collisions between particles is not large.

PMID- 29347494
TI  - Forward, backward, and weighted stochastic bridges.
AB  - We define stochastic bridges as conditional distributions of stochastic paths
      that leave a specified point in phase-space in the past and arrive at another one
      in the future. These can be defined relative to either forward or backward
      stochastic differential equations and with the inclusion of arbitrary path
      dependent weights. The underlying stochastic equations are not the same except in
      linear cases. Accordingly, we generalize the theory of stochastic bridges to
      include time-reversed and weighted stochastic processes. We show that the
      resulting stochastic bridges are identical, whether derived from a forward or a
      backward time stochastic process. A numerical algorithm is obtained to sample
      these distributions. This technique, which uses partial stochastic equations, is
      robust and easily implemented. Examples are given, and comparisons are made to
      previous work. In stochastic equations without a gradient drift, our results
      confirm an earlier conjecture, while generalizing this to cases with path
      dependent weights. An example of a two-dimensional stochastic equation with no
      potential solution is analyzed and numerically solved. We show how this method
      can treat unexpectedly large excursions occurring during a tunneling or escape
      event, in which a system escapes from one quasistable point to arrive at another
      one at a later time.

PMID- 29347495
TI  - Momentum transport and nonlocality in heat-flux-driven magnetic reconnection in
      high-energy-density plasmas.
AB  - Recent theory has demonstrated a novel physics regime for magnetic reconnection
      in high-energy-density plasmas where the magnetic field is advected by heat flux
      via the Nernst effect. Here we elucidate the physics of the electron dissipation
      layer in this regime. Through fully kinetic simulation and a generalized Ohm's
      law derived from first principles, we show that momentum transport due to a
      nonlocal effect, the heat-flux-viscosity, provides the dissipation mechanism for
      magnetic reconnection. Scaling analysis, and simulations show that the
      reconnection process comprises a magnetic field compression stage and quasisteady
      reconnection stage, and the characteristic width of the current sheet in this
      regime is several electron mean-free paths. These results show the important
      interplay between nonlocal transport effects and generation of anisotropic
      components to the distribution function.

PMID- 29347496
TI  - Kinetics of lipid-nanoparticle-mediated intracellular mRNA delivery and function.
AB  - mRNA delivery into cells forms the basis for one of the new and promising ways to
      treat various diseases. Among suitable carriers, lipid nanoparticles (LNPs) with
      a size of about 100 nm are now often employed. Despite high current interest in
      this area, the understanding of the basic details of LNP-mediated mRNA delivery
      and function is limited. To clarify the kinetics of mRNA release from LNPs, the
      author uses three generic models implying (i) exponential, (ii) diffusion
      controlled, and (iii) detachment-controlled kinetic regimes, respectively.
      Despite the distinct differences in these kinetics, the associated transient
      kinetics of mRNA translation to the corresponding protein and its degradation are
      shown to be not too sensitive to the details of the mRNA delivery by LNPs (or
      other nanocarriers). In addition, the author illustrates how this protein may
      temporarily influence the expression of one gene or a few equivalent genes. The
      analysis includes positive or negative regulation of the gene transcription via
      the attachment of the protein without or with positive or negative feedback in
      the gene expression. Stable, bistable, and oscillatory schemes have been
      scrutinized in this context.

PMID- 29347497
TI  - Statistical characterization of discrete conservative systems: The web map.
AB  - We numerically study the two-dimensional, area preserving, web map. When the map
      is governed by ergodic behavior, it is, as expected, correctly described by
      Boltzmann-Gibbs statistics, based on the additive entropic functional
      S_{BG}[p(x)]=-k?dxp(x)lnp(x). In contrast, possible ergodicity breakdown and
      transitory sticky dynamical behavior drag the map into the realm of generalized q
      statistics, based on the nonadditive entropic functional S_{q}[p(x)]=k1
      ?dx[p(x)]^{q}/q-1 (q?R;S_{1}=S_{BG}). We statistically describe the system
      (probability distribution of the sum of successive iterates, sensitivity to the
      initial condition, and entropy production per unit time) for typical values of
      the parameter that controls the ergodicity of the map. For small (large) values
      of the external parameter K, we observe q-Gaussian distributions with q=1.935?
      (Gaussian distributions), like for the standard map. In contrast, for
      intermediate values of K, we observe a different scenario, due to the fractal
      structure of the trajectories embedded in the chaotic sea. Long-standing non
      Gaussian distributions are characterized in terms of the kurtosis and the box
      counting dimension of chaotic sea.

PMID- 29347498
TI  - Plain and oscillatory solitons of the cubic complex Ginzburg-Landau equation with
      nonlinear gradient terms.
AB  - In this work, we present parameter regions for the existence of stable plain
      solitons of the cubic complex Ginzburg-Landau equation (CGLE) with higher-order
      terms associated with a fourth-order expansion. Using a perturbation approach
      around the nonlinear Schrodinger equation soliton and a full numerical analysis
      that solves an ordinary differential equation for the soliton profiles and using
      the Evans method in the search for unstable eigenvalues, we have found that the
      minimum equation allowing these stable solitons is the cubic CGLE plus a term
      known in optics as Raman-delayed response, which is responsible for the redshift
      of the spectrum. The other favorable term for the occurrence of stable solitons
      is a term that represents the increase of nonlinear gain with higher frequencies.
      At the stability boundary, a bifurcation occurs giving rise to stable oscillatory
      solitons for higher values of the nonlinear gain. These oscillations can have
      very high amplitudes, with the pulse energy changing more than two orders of
      magnitude in a period, and they can even exhibit more complex dynamics such as
      period-doubling.

PMID- 29347499
TI  - Synchronized rotation in swarms of magnetotactic bacteria.
AB  - Self-organizing behavior has been widely reported in both natural and artificial
      systems, typically distinguishing between temporal organization (synchronization)
      and spatial organization (swarming). Swarming has been experimentally observed in
      systems of magnetotactic bacteria under the action of external magnetic fields.
      Here we present a model of ensembles of magnetotactic bacteria in which
      hydrodynamic interactions lead to temporal synchronization in addition to the
      swarming. After a period of stabilization during which the bacteria form a
      quasiregular hexagonal lattice structure, the entire swarm begins to rotate in a
      direction opposite to the direction of the rotation of the magnetic field. We
      thus illustrate an emergent mechanism of macroscopic motion arising from the
      synchronized microscopic rotations of hydrodynamically interacting bacteria,
      reminiscent of the recently proposed concept of swarmalators.

PMID- 29347500
TI  - Guidance of microswimmers by wall and flow: Thigmotaxis and rheotaxis of unsteady
      squirmers in two and three dimensions.
AB  - The motions of an unsteady circular-disk squirmer and a spherical squirmer have
      been investigated in the presence of a no-slip infinite wall and a background
      shear flow in order to clarify the similarities and differences between two- and
      three-dimensional motions. Despite the similar bifurcation structure of the
      dynamical system, the stability of the fixed points differs due to the
      Hamiltonian structure of the disk squirmer. Once the unsteady oscillating surface
      velocity profile is considered, the disk squirmer can behave in a chaotic manner
      and cease to be confined in a near-wall region. In contrast, in an unsteady
      spherical squirmer, the dynamics is well attracted by a stable fixed point.
      Additional wall contact interactions lead to stable fixed points for the disk
      squirmer, and, in turn, the surface entrapment of the disk squirmer can be
      stabilized, regardless of the existence of the background flow. Finally, we
      consider spherical motion under a background flow. The separated time scales of
      the surface entrapment (thigmotaxis) and the turning toward the flow direction
      (rheotaxis) enable us to reduce the dynamics to two-dimensional phase space, and
      simple weather-vane mechanics can predict squirmer rheotaxis. The analogous
      structure of the phase plane with the wall contact in two and three dimensions
      implies that the two-dimensional disk swimmer successfully captures the nonlinear
      interactions, and thus two-dimensional approximation could be useful in designing
      microfluidic devices for the guidance of microswimmers and for clarifying the
      locomotions in a complex geometry.

PMID- 29347501
TI  - Dust coupling parameter of radio-frequency-discharge complex plasma under
      microgravity conditions.
AB  - Oscillation of particles in a dust crystal formed in a low-pressure radio
      frequency gas discharge under microgravity conditions is studied. Analysis of
      experimental data obtained in our previous study shows that the oscillations are
      highly isotropic and nearly homogeneous in the bulk of a dust crystal;
      oscillations of the neighboring particles are significantly correlated. We
      demonstrate that the standard deviation of the particle radius vector along with
      the local particle number density fully define the coupling parameter of the
      particle subsystem. The latter proves to be of the order of 100, which is two
      orders of magnitude lower than the coupling parameter estimated for the Brownian
      diffusion of particles with the gas temperature. This means significant kinetic
      overheating of particles under stationary conditions. A theoretical
      interpretation of the large amplitude of oscillation implies the increase of
      particle charge fluctuations in the dust crystal. The theoretical estimates are
      based on the ionization equation of state for the complex plasma and the equation
      for the plasma perturbation evolution. They are shown to match the results of
      experimental data processing. Estimated order of magnitude of the coupling
      parameter accounts for the existence of the solid-liquid phase transition
      observed for similar systems in experiments.

PMID- 29347502
TI  - Topography- and topology-driven spreading of non-Newtonian power-law liquids on a
      flat and a spherical substrate.
AB  - The spreading of a cap-shaped spherical droplet of non-Newtonian power-law
      liquids on a flat and a spherical rough and textured substrate is theoretically
      studied in the capillary-controlled spreading regime. A droplet whose scale is
      much larger than that of the roughness of substrate is considered. The
      equilibrium contact angle on a rough substrate is modeled by the Wenzel and the
      Cassie-Baxter model. Only the viscous energy dissipation within the droplet
      volume is considered, and that within the texture of substrate by imbibition is
      neglected. Then, the energy balance approach is adopted to derive the evolution
      equation of the contact angle. When the equilibrium contact angle vanishes, the
      relaxation of dynamic contact angle theta of a droplet obeys a power-law decay
      theta~t^{-alpha} except for the Newtonian and the non-Newtonian shear-thinning
      liquid of the Wenzel model on a spherical substrate. The spreading exponent alpha
      of the non-Newtonian shear-thickening liquid of the Wenzel model on a spherical
      substrate is larger than others. The relaxation of the Newtonian liquid of the
      Wenzel model on a spherical substrate is even faster showing the exponential
      relaxation. The relaxation of the non-Newtonian shear-thinning liquid of Wenzel
      model on a spherical substrate is fastest and finishes within a finite time.
      Thus, the topography (roughness) and the topology (flat to spherical) of
      substrate accelerate the spreading of droplet.

PMID- 29347503
TI  - Impact-induced solidlike behavior and elasticity in concentrated colloidal
      suspensions.
AB  - Modified drop weight impact tests were performed on SiO_{2}-ethylene glycol
      concentrated suspensions. Counterintuitive impact-induced solidlike behavior and
      elasticity, causing significant deceleration and rebound of the impactor, were
      observed. We provide evidence that the observed large deceleration force on the
      impactor mainly originates from the hydrodynamic force, and that the elasticity
      arises from the short-range repulsive force of a solvation layer on the particle
      surface. This study presents key experimental results to help understand the
      mechanisms underlying various stress-induced solidification phenomena.

PMID- 29347504
TI  - Ion-beam-plasma interaction effects on electrostatic solitary wave propagation in
      ultradense relativistic quantum plasmas.
AB  - Understanding the transport properties of charged particle beams is important not
      only from a fundamental point of view but also due to its relevance in a variety
      of applications. A theoretical model is established in this article, to model the
      interaction of a tenuous positively charged ion beam with an ultradense quantum
      electron-ion plasma, by employing a rigorous relativistic quantum-hydrodynamic
      (fluid plasma) electrostatic model proposed in McKerr et al. [M. McKerr, F. Haas,
      and I. Kourakis, Phys. Rev. E 90, 033112 (2014)PLEEE81539
      375510.1103/PhysRevE.90.033112]. A nonlinear analysis is carried out to elucidate
      the propagation characteristics and the existence conditions of large amplitude
      electrostatic solitary waves propagating in the plasma in the presence of the
      beam. Anticipating stationary profile excitations, a pseudomechanical energy
      balance formalism is adopted to reduce the fluid evolution equation to an
      ordinary differential equation. Exact solutions are thus obtained numerically,
      predicting localized excitations (pulses) for all of the plasma state variables,
      in response to an electrostatic potential disturbance. An ambipolar electric
      field form is also obtained. Thorough analysis of the reality conditions for all
      variables is undertaken in order to determine the range of allowed values for the
      solitonic pulse speed and how it varies as a function of the beam characteristics
      (beam velocity and density).

PMID- 29347505
TI  - Diffusivity of E. coli-like microswimmers in confined geometries: The role of the
      tumbling rate.
AB  - We analyzed the effect of confinement on the effective diffusion of a run-and
      tumble E. coli-like flagellated microswimmer. We used a simulation protocol where
      the run phases are obtained via a fully resolved swimming problem, i.e., Stokes
      equations for the fluid coupled with rigid-body dynamics for the microorganism,
      while tumbles and collisions with the walls are modeled as random reorientation
      of the microswimmer. For weak confinement, the swimmer is trapped in circular
      orbits close to the solid walls. In this case, optimal diffusivity is observed
      when the tumbling frequency is comparable with the angular velocity of the stable
      orbits. For strong confinement, stable circular orbits disappear and the
      diffusion coefficient monotonically decreases with the tumbling rate. Our
      findings are generic and can be potentially applied to other natural or
      artificial chiral microswimmers that follow circular trajectories close to an
      interface or in confined geometries.

PMID- 29347506
TI  - Energy transport in the presence of long-range interactions.
AB  - We study energy transport in the paradigmatic Hamiltonian mean-field (HMF) model
      and other related long-range interacting models using molecular dynamics
      simulations. We show that energy diffusion in the HMF model is subdiffusive in
      nature, which confirms a recently obtained intriguing result that, despite being
      globally interacting, this model is a thermal insulator in the thermodynamic
      limit. Surprisingly, when additional nearest-neighbor interactions are introduced
      to the HMF model, an energy superdiffusion is observed. We show that these
      results can be consistently explained by studying energy localization due to
      thermally generated intrinsic localized excitation modes (discrete breathers) in
      nonlinear discrete systems. Our analysis for the HMF model can also be readily
      extended to more generic long-range interacting models where the interaction
      strength decays algebraically with the (shortest) distance between two lattice
      sites. This reconciles many of the apparently counterintuitive results presented
      recently [C. Olivares and C. Anteneodo, Phys. Rev. E 94, 042117 (2016)2470
      004510.1103/PhysRevE.94.042117; D. Bagchi, Phys. Rev. E 95, 032102 (2017)2470
      004510.1103/PhysRevE.95.032102] concerning energy transport in two such long
      range interacting models.

PMID- 29347507
TI  - Predictability and strength of a heterogeneous system: The role of system size
      and disorder.
AB  - In this paper, I have studied the effect of disorder (delta) and system size (L)
      in a fiber bundle model with a certain range R of stress redistribution. The
      strength of the bundle as well as the failure abruptness is observed with varying
      disorder, stress release range, and system sizes. With a local stress
      concentration, the strength of the bundle is observed to decrease with system
      size. The behavior of such decrements changes drastically as disorder strength is
      tuned. At moderate disorder, sigma_{c} scales with the system size as
      sigma_{c}~1/logL. In low disorder, where the brittle response is highly expected,
      the strength decreases in a scale-free manner (sigma_{c}~1/L). With increasing L
      and R, the model approaches the thermodynamic limit and the mean-field limit,
      respectively. A detailed study shows different limits of the model and the
      corresponding modes of failure on the plane of the above-mentioned parameters
      (delta,L, and R).

PMID- 29347508
TI  - Publisher's Note: Generalized model for k-core percolation and interdependent
      networks [Phys. Rev. E 96, 032317 (2017)].
AB  - This corrects the article DOI: 10.1103/PhysRevE.96.032317.

PMID- 29347509
TI  - Diversity of charge orderings in correlated systems.
AB  - The phenomenon associated with inhomogeneous distribution of electron density is
      known as a charge ordering. In this work, we study the zero-bandwidth limit of
      the extended Hubbard model, which can be considered as a simple effective model
      of charge ordered insulators. It consists of the on-site interaction U and the
      intersite density-density interactions W_{1} and W_{2} between nearest neighbors
      and next-nearest neighbors, respectively. We derived the exact ground state
      diagrams for different lattice dimensionalities and discuss effects of small
      finite temperatures in the limit of high dimensions. In particular, we estimated
      the critical interactions for which new ordered phases emerge (laminar or stripe
      and four-sublattice-type). Our analysis show that the ground state of the model
      is highly degenerated. One of the most intriguing finding is that the nonzero
      temperature removes these degenerations.

PMID- 29347510
TI  - Clustering spectrum of scale-free networks.
AB  - Real-world networks often have power-law degrees and scale-free properties, such
      as ultrasmall distances and ultrafast information spreading. In this paper, we
      study a third universal property: three-point correlations that suppress the
      creation of triangles and signal the presence of hierarchy. We quantify this
      property in terms of c[over -](k), the probability that two neighbors of a degree
      k node are neighbors themselves. We investigate how the clustering spectrum
      k?c[over -](k) scales with k in the hidden-variable model and show that c[over 
      ](k) follows a universal curve that consists of three k ranges where c[over -](k)
      remains flat, starts declining, and eventually settles on a power-law c[over 
      ](k)~k^{-alpha} with alpha depending on the power law of the degree distribution.
      We test these results against ten contemporary real-world networks and explain
      analytically why the universal curve properties only reveal themselves in large
      networks.

PMID- 29347511
TI  - Design of coupling parameters for inducing amplitude death in Cartesian product
      networks of delayed coupled oscillators.
AB  - The present study investigates amplitude death in Cartesian product networks of
      two subnetworks, where each subnetwork has a different coupling delay. The
      property of the Cartesian product helps us to analyze the stability of amplitude
      death. Our analysis reveals that amplitude death can occur for long coupling
      delays if there is a suitable difference in the coupling delays in the two
      subnetworks. Furthermore, based on the edge theorem in robust control theory, we
      propose two design procedures of coupling parameters for inducing amplitude death
      in the Cartesian product networks. Our procedures do not require any information
      of topologies of the subnetworks. The validity of these procedures is numerically
      confirmed.

PMID- 29347512
TI  - Symmetry breaking in two interacting populations of quadratic integrate-and-fire
      neurons.
AB  - We analyze the dynamics of two coupled identical populations of quadratic
      integrate-and-fire neurons, which represent the canonical model for class I
      neurons near the spiking threshold. The populations are heterogeneous; they
      include both inherently spiking and excitable neurons. The coupling within and
      between the populations is global via synapses that take into account the finite
      width of synaptic pulses. Using a recently developed reduction method based on
      the Lorentzian ansatz, we derive a closed system of equations for the neuron's
      firing rates and the mean membrane potentials in both populations. The reduced
      equations are exact in the infinite-size limit. The bifurcation analysis of the
      equations reveals a rich variety of nonsymmetric patterns, including a splay
      state, antiphase periodic oscillations, chimera-like states, and chaotic
      oscillations as well as bistabilities between various states. The validity of the
      reduced equations is confirmed by direct numerical simulations of the finite-size
      networks.

PMID- 29347513
TI  - Coherent motion of chaotic attractors.
AB  - We report a simple model of two drive-response-type coupled chaotic oscillators,
      where the response system copies the nonlinearity of the driver system. It leads
      to a coherent motion of the trajectories of the coupled systems that establishes
      a constant separating distance in time between the driver and the response
      attractors, and their distance depends upon the initial state. The coupled system
      responds to external obstacles, modeled by short-duration pulses acting either on
      the driver or the response system, by a coherent shifting of the distance, and it
      is able to readjust their distance as and when necessary via mutual exchange of
      feedback information. We confirm these behaviors with examples of a jerk system,
      the paradigmatic Rossler system, a tunnel diode system and a Josephson junction
      based jerk system, analytically, to an extent, and mostly numerically.

PMID- 29347514
TI  - Pinning of a drop by a junction on an incline.
AB  - The shape of a drop pinned on an inclined substrate is a long-standing problem
      where the complexity of real surfaces, with heterogeneities and hysteresis, makes
      it complicated to understand the mechanisms behind the phenomena. Here we
      consider the simple case of a drop pinned on an incline at the junction between a
      hydrophilic half plane (the top half) and a hydrophobic one (the bottom half).
      Relying on the equilibrium equations deriving from the balance of forces, we
      exhibit three scenarios depending on the way the contact line of the drop on the
      substrate either simply leans against the junction or overfills (partly or fully)
      into the hydrophobic side. We draw some conclusions on the geometry of the
      overlap and the stability of these tentative equilibrium states. In the
      corresponding retention force factor, we find that a major role is played by the
      wetted length of the junction line, in the spirit of Furmidge's observations. The
      predictions of the theory are compared with extensive molecular dynamics
      simulations.

PMID- 29347515
TI  - Transient response in granular quasi-two-dimensional bounded heap flow.
AB  - We study the transition between steady flows of noncohesive granular materials in
      quasi-two-dimensional bounded heaps by suddenly changing the feed rate. In both
      experiments and simulations, the primary feature of the transition is a wedge of
      flowing particles that propagates downstream over the rising free surface with a
      wedge front velocity inversely proportional to the square root of time. An
      additional longer duration transient process continues after the wedge front
      reaches the downstream wall. The entire transition is well modeled as a moving
      boundary problem with a diffusionlike equation derived from local mass balance
      and a local relation between the flux and the surface slope.

PMID- 29347516
TI  - Resonant activation of population extinctions.
AB  - Understanding the mechanisms governing population extinctions is of key
      importance to many problems in ecology and evolution. Stochastic factors are
      known to play a central role in extinction, but the interactions between a
      population's demographic stochasticity and environmental noise remain poorly
      understood. Here we model environmental forcing as a stochastic fluctuation
      between two states, one with a higher death rate than the other. We find that, in
      general, there exists a rate of fluctuations that minimizes the mean time to
      extinction, a phenomenon previously dubbed "resonant activation." We develop a
      heuristic description of the phenomenon, together with a criterion for the
      existence of resonant activation. Specifically, the minimum extinction time
      arises as a result of the system approaching a scenario wherein the severity of
      rare events is balanced by the time interval between them. We discuss our
      findings within the context of more general forms of environmental noise and
      suggest potential applications to evolutionary models.

PMID- 29347517
TI  - Embedding the dynamics of a single delay system into a feed-forward ring.
AB  - We investigate the relation between the dynamics of a single oscillator with
      delayed self-feedback and a feed-forward ring of such oscillators, where each
      unit is coupled to its next neighbor in the same way as in the self-feedback
      case. We show that periodic solutions of the delayed oscillator give rise to
      families of rotating waves with different wave numbers in the corresponding ring.
      In particular, if for the single oscillator the periodic solution is resonant to
      the delay, it can be embedded into a ring with instantaneous couplings. We
      discover several cases where the stability of a periodic solution for the single
      unit can be related to the stability of the corresponding rotating wave in the
      ring. As a specific example, we demonstrate how the complex bifurcation scenario
      of simultaneously emerging multijittering solutions can be transferred from a
      single oscillator with delayed pulse feedback to multijittering rotating waves in
      a sufficiently large ring of oscillators with instantaneous pulse coupling.
      Finally, we present an experimental realization of this dynamical phenomenon in a
      system of coupled electronic circuits of FitzHugh-Nagumo type.

PMID- 29347518
TI  - Similarity of ensembles of trajectories of reversible and irreversible growth
      processes.
AB  - Models of bacterial growth tend to be "irreversible," allowing for the number of
      bacteria in a colony to increase but not to decrease. By contrast, models of
      molecular self-assembly are usually "reversible," allowing for the addition and
      removal of particles to a structure. Such processes differ in a fundamental way
      because only reversible processes possess an equilibrium. Here we show at the
      mean-field level that dynamic trajectories of reversible and irreversible growth
      processes are similar in that both feel the influence of attractors, at which
      growth proceeds without limit but the intensive properties of the system are
      invariant. Attractors of both processes undergo nonequilibrium phase transitions
      as model parameters are varied, suggesting a unified way of describing typical
      properties of reversible and irreversible growth. We also establish a connection
      at the mean-field level between an irreversible model of growth (the magnetic
      Eden model) and the equilibrium Ising model, supporting the findings made by
      other authors using numerical simulations.

PMID- 29347519
TI  - Environmental rocking ratchet: Environmental rectification by a harmonically
      driven avoided crossing.
AB  - We propose a rocking ratchet designed as a symmetric quantum two-state system
      driven by a single periodic harmonic force and influenced symmetrically by
      thermal fluctuations. We show that the necessary broken symmetry can dynamically
      be achieved by a thermal environment that couples to the energy difference
      between the two states and the tunnel coupling between them. The quantum two
      state system is driven by the harmonic periodic drive through its avoided
      crossing. The correspondingly driven dissipative quantum dynamics results on
      average in a finite population difference between both states. This then causes
      directed particle transport.

PMID- 29347520
TI  - Relativistic analysis of stochastic kinematics.
AB  - The relativistic analysis of stochastic kinematics is developed in order to
      determine the transformation of the effective diffusivity tensor in inertial
      frames. Poisson-Kac stochastic processes are initially considered. For one
      dimensional spatial models, the effective diffusion coefficient measured in a
      frame Sigma moving with velocity w with respect to the rest frame of the
      stochastic process is inversely proportional to the third power of the Lorentz
      factor gamma(w)=(1-w^{2}/c^{2})^{-1/2}. Subsequently, higher-dimensional
      processes are analyzed and it is shown that the diffusivity tensor in a moving
      frame becomes nonisotropic: The diffusivities parallel and orthogonal to the
      velocity of the moving frame scale differently with respect to gamma(w). The
      analysis of discrete space-time diffusion processes permits one to obtain a
      general transformation theory of the tensor diffusivity, confirmed by several
      different simulation experiments. Several implications of the theory are also
      addressed and discussed.

PMID- 29347521
TI  - Inverse problem for multispecies ferromagneticlike mean-field models in phase
      space with many states.
AB  - In this paper we solve the inverse problem for the Curie-Weiss model and its
      multispecies version when multiple thermodynamic states are present as in the low
      temperature phase where the phase space is clustered. The inverse problem
      consists of reconstructing the model parameters starting from configuration data
      generated according to the distribution of the model. We demonstrate that,
      without taking into account the presence of many states, the application of the
      inversion procedure produces very poor inference results. To overcome this
      problem, we use the clustering algorithm. When the system has two symmetric
      states of positive and negative magnetizations, the parameter reconstruction can
      also be obtained with smaller computational effort simply by flipping the sign of
      the magnetizations from positive to negative (or vice versa). The parameter
      reconstruction fails when the system undergoes a phase transition: In that case
      we give the correct inversion formulas for the Curie-Weiss model and we show that
      they can be used to measure how close the system gets to being critical.

PMID- 29347522
TI  - Semiclassical catastrophe theory of simple bifurcations.
AB  - The Fedoriuk-Maslov catastrophe theory of caustics and turning points is extended
      to solve the bifurcation problems by the improved stationary phase method (ISPM).
      The trace formulas for the radial power-law (RPL) potentials are presented by the
      ISPM based on the second- and third-order expansion of the classical action near
      the stationary point. A considerable enhancement of contributions of the two
      orbits (pair consisting of the parent and newborn orbits) at their bifurcation is
      shown. The ISPM trace formula is proposed for a simple bifurcation scenario of
      Hamiltonian systems with continuous symmetries, where the contributions of the
      bifurcating parent orbits vanish upon approaching the bifurcation point due to
      the reduction of the end-point manifold. This occurs since the contribution of
      the parent orbits is included in the term corresponding to the family of the
      newborn daughter orbits. Taking this feature into account, the ISPM level
      densities calculated for the RPL potential model are shown to be in good
      agreement with the quantum results at the bifurcations and asymptotically far
      from the bifurcation points.

PMID- 29347523
TI  - Microstructure and mechanical properties of hyperuniform heterogeneous materials.
AB  - A hyperuniform random heterogeneous material is one in which the local volume
      fraction fluctuations in an observation window decay faster than the reciprocal
      window volume as the window size increases. Recent studies show that this class
      of materials are endowed with superior physical properties such as large
      isotropic photonic band gaps and optimal transport properties. Here we employ a
      stochastic optimization procedure to systematically generate realizations of
      hyperuniform heterogeneous materials with controllable short-range order, which
      is partially quantified using the two-point correlation function S_{2}(r)
      associated with the phase of interest. Specifically, our procedure generalizes
      the widely used Yeong-Torquato reconstruction procedure by including an
      additional constraint for hyperuniformity, i.e., the volume integral of the
      autocovariance function chi(r)=S_{2}(r)-phi^{2} over the whole space is zero. In
      addition, we only require the reconstructed S_{2} to match the target function up
      to a certain cutoff distance gamma, in order to give the system sufficient
      degrees of freedom to satisfy the hyperuniform condition. By systematically
      increasing the gamma value for a given S_{2}, one can produce a spectrum of
      hyperuniform heterogeneous materials with varying degrees of partial short-range
      order compatible with the specified S_{2}. The mechanical performance including
      both elastic and brittle fracture behaviors of the generated hyperuniform
      materials is analyzed using a volume-compensated lattice-particle method. For the
      purpose of comparison, the corresponding nonhyperuniform materials with the same
      short-range order (i.e., with S_{2} constrained up to the same gamma value) are
      also constructed and their mechanical performance is analyzed. Here we consider
      two specific S_{2} including the positive exponential decay function and the
      correlation function associated with an equilibrium hard-sphere system. For the
      constructed systems associated with these two specific functions, we find that
      although the hyperuniform materials are softer than their nonhyperuniform
      counterparts, the former generally possess a significantly higher brittle
      fracture strength than the latter. This superior mechanical behavior is
      attributed to the lower degree of stress concentration in the material resulting
      from the hyperuniform microstructure, which is crucial to crack initiation and
      propagation.

PMID- 29347524
TI  - Effect of high-order dispersion on three-soliton interactions for the variable
      coefficients Hirota equation.
AB  - The interactions of multiple solitons show different properties with two-soliton
      interactions. For the difficulty of deriving multiple soliton solutions, it is
      rare to study multiple soliton interactions analytically. In this paper, three
      soliton interactions in inhomogeneous optical fibers, which are described by the
      variable coefficient Hirota equation, are investigated. Via the Hirota bilinear
      method and symbolic computation, analytic three-soliton solutions are obtained.
      According to the obtained solutions, properties and features of three-soliton
      interactions are discussed by changing the third-order dispersion (TOD) and other
      relevant coefficients, and some plentiful structure of three-soliton interactions
      are presented for the first time. The influences of TOD on the intensity and
      propagation distance of solitons are described, which can be used to realize the
      soliton control. Besides, the method that can achieve the phase reverse of
      solitons is suggested, and bound states of three solitons are observed, which
      have potential applications in the mode-locked fiber lasers. Furthermore,
      comparing to two-soliton interactions, a novel phenomenon of three-soliton
      interactions with a strong phase shift at x=0 is revealed, which is potentially
      useful for optical logic switches.

PMID- 29347525
TI  - Network patterns in exponentially growing two-dimensional biofilms.
AB  - Anisotropic collective patterns occur frequently in the morphogenesis of two
      dimensional biofilms. These patterns are often attributed to growth regulation
      mechanisms and differentiation based on gradients of diffusing nutrients and
      signaling molecules. Here, we employ a model of bacterial growth dynamics to show
      that even in the absence of growth regulation or differentiation, confinement by
      an enclosing medium such as agar can itself lead to stable pattern formation over
      time scales that are employed in experiments. The underlying mechanism relies on
      path formation through physical deformation of the enclosing environment.

PMID- 29347526
TI  - Limit regimes of ice formation in turbulent supercooled water.
AB  - A study of ice formation in stationary turbulent conditions is carried out in
      various limit regimes of crystal growth, supercooling, and ice entrainment at the
      water surface. Analytical expressions for the temperature, salinity, and ice
      concentration mean profiles are provided, and the role of fluctuations in ice
      production is numerically quantified. Lower bounds on the ratio of sensible heat
      flux to latent heat flux to the atmosphere are derived and their dependence on
      key parameters such as salt rejection in freezing and ice entrainment in the
      water column is elucidated.

PMID- 29347527
TI  - Collisional damping rates for electron plasma waves reassessed.
AB  - Collisional damping of electron plasma waves, the primary damping for high phase
      velocity waves, is proportional to the electron-ion collision rate, nu_{ei,th}.
      Here, it is shown that the damping rate normalized to nu_{ei,th} depends on the
      charge state, Z, on the magnitude of nu_{ei,th} and the wave number k in contrast
      with the commonly used damping rate in plasma wave research. Only for weak
      collision rates in low-Z plasmas for which the electron self-collision rate is
      comparable to the electron-ion collision rate is the damping rate given by the
      commonly accepted value. The result presented here corrects the result presented
      in textbooks at least as early as 1973. The complete linear theory requires the
      inclusion of both electron-ion pitch-angle and electron-electron scattering,
      which itself contains contributions to both pitch-angle scattering and
      thermalization.

PMID- 29347528
TI  - Quantum work fluctuations in connection with the Jarzynski equality.
AB  - A result of great theoretical and experimental interest, the Jarzynski equality
      predicts a free energy change DeltaF of a system at inverse temperature beta from
      an ensemble average of nonequilibrium exponential work, i.e., <e^{-betaW}>=e^{
      betaDeltaF}. The number of experimental work values needed to reach a given
      accuracy of DeltaF is determined by the variance of e^{-betaW}, denoted var(e^{
      betaW}). We discover in this work that var(e^{-betaW}) in both harmonic and
      anharmonic Hamiltonian systems can systematically diverge in nonadiabatic work
      protocols, even when the adiabatic protocols do not suffer from such divergence.
      This divergence may be regarded as a type of dynamically induced phase transition
      in work fluctuations. For a quantum harmonic oscillator with time-dependent
      trapping frequency as a working example, any nonadiabatic work protocol is found
      to yield a diverging var(e^{-betaW}) at sufficiently low temperatures, markedly
      different from the classical behavior. The divergence of var(e^{-betaW})
      indicates the too-far-from-equilibrium nature of a nonadiabatic work protocol and
      makes it compulsory to apply designed control fields to suppress the quantum work
      fluctuations in order to test the Jarzynski equality.

PMID- 29347529
TI  - Percolation thresholds in hyperbolic lattices.
AB  - We use invasion percolation to compute numerical values for bond and site
      percolation thresholds p_{c} (existence of an infinite cluster) and p_{u}
      (uniqueness of the infinite cluster) of tesselations {P,Q} of the hyperbolic
      plane, where Q faces meet at each vertex and each face is a P-gon. Our values are
      accurate to six or seven decimal places, allowing us to explore their functional
      dependency on P and Q and to numerically compute critical exponents. We also
      prove rigorous upper and lower bounds for p_{c} and p_{u} that can be used to
      find the scaling of both thresholds as a function of P and Q.

PMID- 29347530
TI  - Stochastic efficiency of an isothermal work-to-work converter engine.
AB  - We investigate the efficiency of an isothermal Brownian work-to-work converter
      engine, composed of a Brownian particle coupled to a heat bath at a constant
      temperature. The system is maintained out of equilibrium by using two external
      time-dependent stochastic Gaussian forces, where one is called load force and the
      other is called drive force. Work done by these two forces are stochastic
      quantities. The efficiency of this small engine is defined as the ratio of
      stochastic work done against load force to stochastic work done by the drive
      force. The probability density function as well as large deviation function of
      the stochastic efficiency are studied analytically and verified by numerical
      simulations.

PMID- 29347531
TI  - Local-stability analysis of a low-dissipation heat engine working at maximum
      power output.
AB  - In this paper we address the stability of a low-dissipation (LD) heat engine (HE)
      under maximum power conditions. The LD system dynamics are analyzed in terms of
      the contact times between the engine and the external heat reservoirs, which
      determine the amount of heat exchanged by the system. We study two different
      scenarios that secure the existence of a single stable steady state. In these
      scenarios, contact times dynamics are governed by restitutive forces that are
      linear functions of either the heat amounts exchanged per cycle, or the
      corresponding heat fluxes. In the first case, according to our results,
      preferably locating the system irreversibility sources at the hot-reservoir
      coupling improves the system stability and increases its efficiency. On the other
      hand, reducing the thermal gradient increases the system efficiency but
      deteriorates its stability properties, because the restitutive forces are
      smaller. Additionally, it is possible to compare the relaxation times with the
      total cycle time and obtain some constraints upon the system dynamics. In the
      second case, where the restitutive forces are assumed to be linear functions of
      the heat fluxes, we find that although the partial contact time presents a
      locally stable stationary value, the total cycle time does not; instead, there
      exists an infinite collection of steady values located in the neighborhood of the
      fixed point, along a one-dimensional manifold. Finally, the role of dissipation
      asymmetries on the efficiency, the stability, and the ratio of the total cycle
      time to the relaxation time is emphasized.

PMID- 29347532
TI  - Dual lattice functional renormalization group for the Berezinskii-Kosterlitz
      Thouless transition: Irrelevance of amplitude and out-of-plane fluctuations.
AB  - We develop a functional renormalization group (FRG) approach for the two
      dimensional XY model by combining the lattice FRG proposed by Machado and Dupuis
      [Phys. Rev. E 82, 041128 (2010)PLEEE81539-375510.1103/PhysRevE.82.041128] with a
      duality transformation that explicitly introduces vortices via an integer-valued
      field. We show that the hierarchy of FRG flow equations for the infinite set of
      relevant and marginal couplings of the model can be reduced to the well-known
      Kosterlitz-Thouless renormalization group equations for the renormalized
      temperature and the vortex fugacity. Within our approach it is straightforward to
      include weak amplitude as well as out-of-plane fluctuations of the spins, which
      lead to additional interactions between the vortices that do not spoil the
      Berezinskii-Kosterlitz-Thouless transition. This demonstrates that previous
      failures to obtain a line of true fixed points within the FRG are a mathematical
      artifact of insufficient truncation schemes.

PMID- 29347533
TI  - Model of chromosomal loci dynamics in bacteria as fractional diffusion with
      intermittent transport.
AB  - The short-time dynamics of bacterial chromosomal loci is a mixture of
      subdiffusive and active motion, in the form of rapid relocations with near
      ballistic dynamics. While previous work has shown that such rapid motions are
      ubiquitous, we still have little grasp on their physical nature, and no positive
      model is available that describes them. Here, we propose a minimal theoretical
      model for loci movements as a fractional Brownian motion subject to a constant
      but intermittent driving force, and compare simulations and analytical
      calculations to data from high-resolution dynamic tracking in E. coli. This
      analysis yields the characteristic time scales for intermittency. Finally, we
      discuss the possible shortcomings of this model, and show that an increase in the
      effective local noise felt by the chromosome associates to the active
      relocations.

PMID- 29347534
TI  - Exponential bound in the quest for absolute zero.
AB  - In most studies for the quantification of the third law of thermodynamics, the
      minimum temperature which can be achieved with a long but finite-time process
      scales as a negative power of the process duration. In this article, we use our
      recent complete solution for the optimal control problem of the quantum
      parametric oscillator to show that the minimum temperature which can be obtained
      in this system scales exponentially with the available time. The present work is
      expected to motivate further research in the active quest for absolute zero.

PMID- 29347535
TI  - Publisher's Note: Spreading law of non-Newtonian power-law liquids on a spherical
      substrate by an energy-balance approach [Phys. Rev. E 96, 012803 (2017)].
AB  - This corrects the article DOI: 10.1103/PhysRevE.96.012803.

PMID- 29347536
TI  - Force fluctuations on a wall in interaction with a granular lid-driven cavity
      flow.
AB  - The force fluctuations experienced by a boundary wall subjected to a lid-driven
      cavity flow are investigated by means of numerical simulations based on the
      discrete-element method. The time-averaged dynamics inside the cavity volume and
      the resulting steady force on the wall are governed by the boundary macroscopic
      inertial number, the latter being derived from the shearing velocity and the
      confinement pressure imposed at the top. The force fluctuations are quantified
      through measuring both the autocorrelation of force time series and the
      distributions of grain-wall forces, at distinct spatial scales from particle
      scale to wall scale. A key result is that the grain-wall force distributions are
      entirely driven by the boundary macroscopic inertial number, whatever the spatial
      scale considered. In particular, when the wall scale is considered, the
      distributions are found to evolve from nearly exponential to nearly Gaussian
      distributions by decreasing the macroscopic inertial number. The transition from
      quasistatic to dense inertial flow is well identified through remarkable changes
      in the shapes of the distributions of grain-wall forces, accompanied by a loss of
      system memory in terms of the mesoscale force transmitted toward the wall.

PMID- 29347537
TI  - Ordering kinetics in the random-bond XY model.
AB  - We present a comprehensive Monte Carlo study of domain growth in the random-bond
      XY model with nonconserved kinetics. The presence of quenched disorder slows down
      domain growth in d=2,3. In d=2, we observe power-law growth with a disorder
      dependent exponent on the time scales of our simulation. In d=3, we see the
      signature of an asymptotically logarithmic growth regime. The scaling functions
      for the real-space correlation function are seen to be independent of the
      disorder. However, the same does not apply for the two-time autocorrelation
      function, demonstrating the breakdown of superuniversality.

PMID- 29347538
TI  - Refined energy-conserving dissipative particle dynamics model with temperature
      dependent properties and its application in solidification problem.
AB  - It has been observed previously that the physical behaviors of Schmidt number
      (Sc) and Prandtl number (Pr) of an energy-conserving dissipative particle
      dynamics (eDPD) fluid can be reproduced by the temperature-dependent weight
      function appearing in the dissipative force term. In this paper, we proposed a
      simple and systematic method to develop the temperature-dependent weight function
      in order to better reproduce the physical fluid properties. The method was then
      used to study a variety of phase-change problems involving solidification. The
      concept of the "mushy" eDPD particle was introduced in order to better capture
      the temperature profile in the vicinity of the solid-liquid interface,
      particularly for the case involving high thermal conductivity ratio. Meanwhile, a
      way to implement the constant temperature boundary condition at the wall was
      presented. The numerical solutions of one- and two-dimensional solidification
      problems were then compared with the analytical solutions and/or experimental
      results and the agreements were promising.

PMID- 29347539
TI  - Theory of nanobubble formation and induced force in nanochannels.
AB  - This paper presents a fundamental theory of nanobubble formation and induced
      force in confined nanochannels. It is shown that nanobubble formation between
      hydrophobic plates can be predicted from their surface tension and geometry, with
      estimated values for the surface free energy and the force acting on the plates
      in good agreement with the results of molecular dynamics simulation and
      experimentation. When a bubble is formed between two plates, vertical attractive
      force and horizontal retract force due to the shifted plates are applied to the
      plates. The net force exerted on the plates is not dependent on the distance
      between them. The short-range force between hydrophobic surfaces due to
      hydrophobic interaction appears to correspond to the force estimated by our
      theory. We compared between experimental and theoretical values for the binding
      energy of a molecular motor system to validate our theory. The tendency that the
      binding energy increases as the size of the protein increases is consistent with
      the theory.

PMID- 29347540
TI  - Compliant contact versus rigid contact: A comparison in the context of granular
      dynamics.
AB  - We summarize and numerically compare two approaches for modeling and simulating
      the dynamics of dry granular matter. The first one, the discrete-element method
      via penalty (DEM-P), is commonly used in the soft matter physics and geomechanics
      communities; it can be traced back to the work of Cundall and Strack [P. Cundall,
      Proc. Symp. ISRM, Nancy, France 1, 129 (1971); P. Cundall and O. Strack,
      Geotechnique 29, 47 (1979)GTNQA80016-850510.1680/geot.1979.29.1.47]. The second
      approach, the discrete-element method via complementarity (DEM-C), considers the
      grains perfectly rigid and enforces nonpenetration via complementarity
      conditions; it is commonly used in robotics and computer graphics applications
      and had two strong promoters in Moreau and Jean [J. J. Moreau, in Nonsmooth
      Mechanics and Applications, edited by J. J. Moreau and P. D. Panagiotopoulos
      (Springer, Berlin, 1988), pp. 1-82; J. J. Moreau and M. Jean, Proceedings of the
      Third Biennial Joint Conference on Engineering Systems and Analysis, Montpellier,
      France, 1996, pp. 201-208]. The DEM-P and DEM-C are manifestly unlike each other:
      They use different (i) approaches to model the frictional contact problem, (ii)
      sets of model parameters to capture the physics of interest, and (iii) classes of
      numerical methods to solve the differential equations that govern the dynamics of
      the granular material. Herein, we report numerical results for five experiments:
      shock wave propagation, cone penetration, direct shear, triaxial loading, and
      hopper flow, which we use to compare the DEM-P and DEM-C solutions. This exercise
      helps us reach two conclusions. First, both the DEM-P and DEM-C are predictive,
      i.e., they predict well the macroscale emergent behavior by capturing the
      dynamics at the microscale. Second, there are classes of problems for which one
      of the methods has an advantage. Unlike the DEM-P, the DEM-C cannot capture shock
      wave propagation through granular media. However, the DEM-C is proficient at
      handling arbitrary grain geometries and solves, at large integration step sizes,
      smaller problems, i.e., containing thousands of elements, very effectively. The
      DEM-P vs DEM-C comparison is carried out using a public-domain, open-source
      software package; the models used are available online.

PMID- 29347541
TI  - Solid ^{4}He and the diffusion Monte Carlo method: A study of their properties.
AB  - Properties of helium atoms in the solid phase are investigated using the
      multiweight diffusion Monte Carlo method. Two different importance function
      transformations are used in two series of independent calculations. The kinetic
      energy is estimated for both the solid and liquid phases of ^{4}He. We estimate
      the melting and freezing densities, among other properties of interest. Our
      estimates are compared with experimental values. We discuss why walkers biased by
      two distinctly different guiding functions do not lead to noticeable changes in
      the reported results. Criticisms concerning the bias introduced into our
      estimates by population control and system size effects are considered.

PMID- 29347542
TI  - Breather solutions of a fourth-order nonlinear Schrodinger equation in the
      degenerate, soliton, and rogue wave limits.
AB  - We present one- and two-breather solutions of the fourth-order nonlinear
      Schrodinger equation. With several parameters to play with, the solution may take
      a variety of forms. We consider most of these cases including the general form
      and limiting cases when the modulation frequencies are 0 or coincide. The zero
      frequency limit produces a combination of breather-soliton structures on a
      constant background. The case of equal modulation frequencies produces a
      degenerate solution that requires a special technique for deriving. A zero
      frequency limit of this degenerate solution produces a rational second-order
      rogue wave solution with a stretching factor involved. Taking, in addition, the
      zero limit of the stretching factor transforms the second-order rogue waves into
      a soliton. Adding a differential shift in the degenerate solution results in
      structural changes in the wave profile. Moreover, the zero-frequency limit of the
      degenerate solution with differential shift results in a rogue wave triplet. The
      zero limit of the stretching factor in this solution, in turn, transforms the
      triplet into a singlet plus a low-amplitude soliton on the background. A large
      value of the differential shift parameter converts the triplet into a pure
      singlet.

PMID- 29347543
TI  - Cover time for random walks on arbitrary complex networks.
AB  - We present an analytical method for computing the mean cover time of a discrete
      time random walk process on arbitrary, complex networks. The cover time is
      defined as the time a random walker requires to visit every node in the network
      at least once. This quantity is particularly important for random search
      processes and target localization on network structures. Based on the global mean
      first-passage time of target nodes, we derive a method for computing the
      cumulative distribution function of the cover time based on first-passage time
      statistics. Our method is viable for networks on which random walks equilibrate
      quickly. We show that it can be applied successfully to various model and real
      world networks. Our results reveal an intimate link between first-passage and
      cover time statistics and offer a computationally efficient way for estimating
      cover times in network-related applications.

PMID- 29347544
TI  - Adiabatic elimination of inertia of the stochastic microswimmer driven by alpha
      stable noise.
AB  - We consider a microswimmer that moves in two dimensions at a constant speed and
      changes the direction of its motion due to a torque consisting of a constant and
      a fluctuating component. The latter will be modeled by a symmetric Levy-stable
      (alpha-stable) noise. The purpose is to develop a kinetic approach to eliminate
      the angular component of the dynamics to find a coarse-grained description in the
      coordinate space. By defining the joint probability density function of the
      position and of the orientation of the particle through the Fokker-Planck
      equation, we derive transport equations for the position-dependent marginal
      density, the particle's mean velocity, and the velocity's variance. At time
      scales larger than the relaxation time of the torque tau_{phi}, the two higher
      moments follow the marginal density and can be adiabatically eliminated. As a
      result, a closed equation for the marginal density follows. This equation, which
      gives a coarse-grained description of the microswimmer's positions at time scales
      t?tau_{phi}, is a diffusion equation with a constant diffusion coefficient
      depending on the properties of the noise. Hence, the long-time dynamics of a
      microswimmer can be described as a normal, diffusive, Brownian motion with
      Gaussian increments.

PMID- 29347545
TI  - Erratum: Bypass rewiring and robustness of complex networks [Phys. Rev. E 94,
      022310 (2016)].
AB  - This corrects the article DOI: 10.1103/PhysRevE.94.022310.

PMID- 29347546
TI  - Phase transitions in systems with aggregation and shattering.
AB  - We consider a system of clusters made of elementary building blocks, monomers,
      and evolving via collisions between diffusing monomers and immobile composite
      clusters. In our model, the cluster-monomer collision can lead to the attachment
      of the monomer to the cluster (addition process) or to the total breakup of the
      cluster (shattering process). A phase transition, separating qualitatively
      different behaviors, occurs when the probability of shattering events exceeds a
      certain threshold. The novel feature of the phase transition is the dramatic
      dependence on the initial conditions.

PMID- 29347547
TI  - Observations of cavity polaritons in one-dimensional photonic crystals containing
      a liquid-crystalline semiconductor based on perylene bisimide units.
AB  - We investigated the optical transmission properties of one-dimensional photonic
      crystal (1D-PC) microcavity structures containing the liquid-crystalline (LC)
      perylene tetracarboxylic bisimide (PTCBI) derivative. We fabricated the
      microcavity structures for this study by two different methods and observed the
      cavity polaritons successfully in both samples. For one sample, since the PTCBI
      molecules were aligned in the cavity layer of the 1D-PC by utilizing a friction
      transfer method, vacuum Rabi splitting energy was strongly dependent on the
      polarization of the incident light produced by the peculiar optical features of
      the LC organic semiconductor. For the other sample, we did not utilize the
      friction transfer method and did not observe such polarization dependence.
      However, we did observe a relatively large Rabi splitting energy of 187 meV,
      probably due to the improvement of optical confinement effect.

PMID- 29347548
TI  - Temperature dependence of the Landau-Placzek ratio in liquid water.
AB  - Rayleigh-Brillouin light scattering is studied in liquid water over the range
      from 249 to 365 K. Experiments are carried out with a high spectral resolution
      (0.1 GHz), eliminating any contribution of the structural relaxation to the
      elastic line. The Landau-Placzek ratio is found as the ratio of the Rayleigh and
      Brillouin intensities. In the whole temperature range, the Landau-Placzek ratio
      is found to be in good agreement with a prediction of the theory with a pair of
      independent thermodynamic variables, pressure and entropy. This description is
      usually used for single-component homogeneous liquids. An excess of the Landau
      Placzek ratio above the prediction is expected for inhomogeneous liquids and is
      observed, for example, in glass-forming liquids below a certain temperature. In
      contrast to glass-forming liquids, no excess of elastically scattered light
      increasing at low temperatures is observed for the Landau-Placzek ratio of water.
      This suggests that the Landau-Placzek ratio of liquid water can be described by a
      homogeneous structure, and the idea of the water structure consisting of two
      structural motifs may not be necessary to explain the experimental ratio.

PMID- 29347549
TI  - Multiscale permutation entropy analysis of laser beam wandering in isotropic
      turbulence.
AB  - We have experimentally quantified the temporal structural diversity from the
      coordinate fluctuations of a laser beam propagating through isotropic optical
      turbulence. The main focus here is on the characterization of the long-range
      correlations in the wandering of a thin Gaussian laser beam over a screen after
      propagating through a turbulent medium. To fulfill this goal, a laboratory
      controlled experiment was conducted in which coordinate fluctuations of the laser
      beam were recorded at a sufficiently high sampling rate for a wide range of
      turbulent conditions. Horizontal and vertical displacements of the laser beam
      centroid were subsequently analyzed by implementing the symbolic technique based
      on ordinal patterns to estimate the well-known permutation entropy. We show that
      the permutation entropy estimations at multiple time scales evidence an interplay
      between different dynamical behaviors. More specifically, a crossover between two
      different scaling regimes is observed. We confirm a transition from an integrated
      stochastic process contaminated with electronic noise to a fractional Brownian
      motion with a Hurst exponent H=5/6 as the sampling time increases. Besides, we
      are able to quantify, from the estimated entropy, the amount of electronic noise
      as a function of the turbulence strength. We have also demonstrated that these
      experimental observations are in very good agreement with numerical simulations
      of noisy fractional Brownian motions with a well-defined crossover between two
      different scaling regimes.

PMID- 29347550
TI  - Stochastic maps, continuous approximation, and stable distribution.
AB  - A continuous approximation framework for general nonlinear stochastic as well as
      deterministic discrete maps is developed. For the stochastic map with uncorelated
      Gaussian noise, by successively applying the Ito lemma, we obtain a Langevin type
      of equation. Specifically, we show how nonlinear maps give rise to a Langevin
      description that involves multiplicative noise. The multiplicative nature of the
      noise induces an additional effective force, not present in the absence of noise.
      We further exploit the continuum description and provide an explicit formula for
      the stable distribution of the stochastic map and conditions for its existence.
      Our results are in good agreement with numerical simulations of several maps.

PMID- 29347551
TI  - Tensile elasticity of semiflexible polymers with hinge defects.
AB  - It has become clear in recent years that the simple uniform wormlike chain model
      needs to be modified in order to account for more complex behavior which has been
      observed experimentally in some important biopolymers. For example, the large
      flexibility of short ds-DNA has been attributed to kink or hinge defects. In this
      paper, we calculate analytically, within the weak bending approximation, the
      force-extension relation of a wormlike chain with a permanent hinge defect along
      its contour. The defect is characterized by its bending energy (which can be
      zero, in the completely flexible case) and its position along the polymer
      contour. Besides the bending rigidity of the chain, these are the only parameters
      which describe our model. We show that a hinge defect causes a significant
      increase in the differential tensile compliance of a prestressed chain. In the
      small force limit, a hinge defect significantly increases the entropic
      elasticity. Our results apply to any pair of semiflexible segments connected by a
      hinge. As such, they may also be relevant to cytoskeletal filaments (F-actin,
      microtubules), where one may treat the cross-link connecting two filaments as a
      hinge defect.

PMID- 29347552
TI  - Complete diagrammatics of the single-ring theorem.
AB  - Using diagrammatic techniques, we provide explicit functional relations between
      the cumulant generating functions for the biunitarily invariant ensembles in the
      limit of large size of matrices. The formalism allows us to map two distinct
      areas of free random variables: Hermitian positive definite operators and non
      normal R-diagonal operators. We also rederive the Haagerup-Larsen theorem and
      show how its recent extension to the eigenvector correlation function appears
      naturally within this approach.

PMID- 29347553
TI  - Instabilities of convection patterns in a shear-thinning fluid between plates of
      finite conductivity.
AB  - Rayleigh-Benard convection in a horizontal layer of a non-Newtonian fluid between
      slabs of arbitrary thickness and finite thermal conductivity is considered. The
      first part of the paper deals with the primary bifurcation and the relative
      stability of convective patterns at threshold. Weakly nonlinear analysis combined
      with Stuart-Landau equation is used. The competition between squares and rolls,
      as a function of the shear-thinning degree of the fluid, the slabs' thickness,
      and the ratio of the thermal conductivity of the slabs to that of the fluid is
      investigated. Computations of heat transfer coefficients are in agreement with
      the maximum heat transfer principle. The second part of the paper concerns the
      stability of the convective patterns toward spatial perturbations and the
      determination of the band width of the stable wave number in the neighborhood of
      the critical Rayleigh number. The approach used is based on the Ginzburg-Landau
      equations. The study of rolls stability shows that: (i) for low shear-thinning
      effects, the band of stable wave numbers is bounded by zigzag instability and
      cross-roll instability. Furthermore, the marginal cross-roll stability boundary
      enlarges with increasing shear-thinning properties; (ii) for high shear-thinning
      effects, Eckhaus instability becomes more dangerous than cross-roll instability.
      For square patterns, the wave number selection is always restricted by zigzag
      instability and by "rectangular Eckhaus" instability. In addition, the width of
      the stable wave number decreases with increasing shear-thinning effects.
      Numerical simulations of the planform evolution are also presented to illustrate
      the different instabilities considered in the paper.

PMID- 29347554
TI  - Action at a distance in classical uniaxial ferromagnetic arrays.
AB  - We examine in detail the theoretical foundations of striking long-range couplings
      emerging in arrays of fluid cells connected by narrow channels by using a lattice
      gas (Ising model) description of a system. We present a reexamination of the well
      known exact determination of the two-point correlation function along the edge of
      a channel using the transfer matrix technique and a different interpretation is
      provided. The explicit form of the correlation length is found to grow
      exponentially with the cross section of the channels at the bulk two-phase
      coexistence. The aforementioned result is recaptured by a refined version of the
      Fisher-Privman theory of first order phase transitions in which the Boltzmann
      factor for a domain wall is decorated with a contribution stemming from the point
      tension originated at its end points. The Boltzmann factor for a domain wall
      together with the point tension is then identified exactly thanks to two
      independent analytical techniques, providing a critical test of the Fisher
      Privman theory. We then illustrate how to build up the network model from its
      elementary constituents, the cells and the channels. Moreover, we are able to
      extract the strength of the coupling between cells and express them in terms of
      the length and width and coarse-grained quantities such as surface and point
      tensions. We then support our theoretical investigation with a series of
      corroborating results based on Monte Carlo simulations. We illustrate how the
      long-range ordering occurs and how the latter is signaled by the thermodynamic
      quantities corresponding to both planar and three-dimensional Ising arrays.

PMID- 29347555
TI  - Morphing continuum theory for turbulence: Theory, computation, and visualization.
AB  - A high order morphing continuum theory (MCT) is introduced to model highly
      compressible turbulence. The theory is formulated under the rigorous framework of
      rational continuum mechanics. A set of linear constitutive equations and balance
      laws are deduced and presented from the Coleman-Noll procedure and Onsager's
      reciprocal relations. The governing equations are then arranged in conservation
      form and solved through the finite volume method with a second-order Lax
      Friedrichs scheme for shock preservation. A numerical example of transonic flow
      over a three-dimensional bump is presented using MCT and the finite volume
      method. The comparison shows that MCT-based direct numerical simulation (DNS)
      provides a better prediction than Navier-Stokes (NS)-based DNS with less than 10%
      of the mesh number when compared with experiments. A MCT-based and frame
      indifferent Q criterion is also derived to show the coherent eddy structure of
      the downstream turbulence in the numerical example. It should be emphasized that
      unlike the NS-based Q criterion, the MCT-based Q criterion is objective without
      the limitation of Galilean invariance.

PMID- 29347556
TI  - One-dimensional description of driven diffusion in periodic channels.
AB  - Diffusion of point-like particles driven by a constant longitudinal force in two
      dimensional channels of periodically varying width is studied. The dynamics of
      such systems can be effectively described by the one-dimensional Smoluchowski(
      Fick-Jacobs) equation in the longitudinal coordinate x, extended by a space
      dependent effective diffusion coefficient D(x). Our paper is focused on
      calculation of this function for an arbitrary channel shaping function h(x).
      Unlike the previous algorithms based on scaling of the transverse lengths, the
      method presented here uses periodicity of the channel. Instead of complicated
      expansion containing higher order derivatives of h(x), the proposed algorithm
      results in an integral formula for D(x), enabling us to study the system for wide
      range of the driving force and various (periodic) shaping functions h(x).

PMID- 29347557
TI  - Constant-pressure nested sampling with atomistic dynamics.
AB  - The nested sampling algorithm has been shown to be a general method for
      calculating the pressure-temperature-composition phase diagrams of materials.
      While the previous implementation used single-particle Monte Carlo moves, these
      are inefficient for condensed systems with general interactions where single
      particle moves cannot be evaluated faster than the energy of the whole system.
      Here we enhance the method by using all-particle moves: either Galilean Monte
      Carlo or the total enthalpy Hamiltonian Monte Carlo algorithm, introduced in this
      paper. We show that these algorithms enable the determination of phase transition
      temperatures with equivalent accuracy to the previous method at 1/N of the cost
      for an N-particle system with general interactions, or at equal cost when single
      particle moves can be done in 1/N of the cost of a full N-particle energy
      evaluation. We demonstrate this speed-up for the freezing and condensation
      transitions of the Lennard-Jones system and show the utility of the algorithms by
      calculating the order-disorder phase transition of a binary Lennard-Jones model
      alloy, the eutectic of copper-gold, the density anomaly of water, and the
      condensation and solidification of bead-spring polymers. The nested sampling
      method with all three algorithms is implemented in the pymatnest software.

PMID- 29347558
TI  - Complete delocalization in a defective periodic structure.
AB  - We report on the existence of stable, completely delocalized response regimes in
      a nonlinear defective periodic structure. In this state of complete
      delocalization, despite the presence of the defect, the system exhibits in-phase
      oscillation of all units with the same amplitude. This elimination of defect
      borne localization may occur in both the free and forced responses of the system.
      In the absence of external driving, the localized defect mode becomes completely
      delocalized at a certain energy level. In the case of a damped-driven system,
      complete delocalization may be realized if the driving amplitude is beyond a
      certain threshold. We demonstrate this phenomenon numerically in a linear
      periodic structure with one and two defective units possessing a nonlinear
      restoring force. We derive closed-form analytical expressions for the onset of
      complete delocalization, and we discuss the necessary conditions for its
      occurrence.

PMID- 29347559
TI  - How anisotropy beats fractality in two-dimensional on-lattice diffusion-limited
      aggregation growth.
AB  - We study the fractal structure of diffusion-limited aggregation (DLA) clusters on
      a square lattice by extensive numerical simulations (with clusters having up to
      10^{8} particles). We observe that DLA clusters undergo strongly anisotropic
      growth, with the maximal growth rate along the axes. The naive scaling limit of a
      DLA cluster by its diameter is thus deterministic and one-dimensional. At the
      same time, on all scales from the particle size to the size of the entire cluster
      it has a nontrivial box-counting fractal dimension which corresponds to the
      overall growth rate, which, in turn, is smaller than the growth rate along the
      axes. This suggests that the fractal nature of the lattice DLA should be
      understood in terms of fluctuations around the one-dimensional backbone of the
      cluster.

PMID- 29347560
TI  - Effect of capillary condensation on gas transport properties in porous media.
AB  - We investigate the effect of capillary condensation on gas diffusivity in porous
      media composed of randomly packed spheres with moderate wettability. To simulate
      capillary phenomena at the pore scale while retaining complex pore networks of
      the porous media, we employ density functional theory (DFT) for coarse-grained
      lattice gas models. The lattice DFT simulations reveal that capillary
      condensations preferentially occur at confined pores surrounded by solid walls,
      leading to the occlusion of narrow pores. Consequently, the characteristic
      lengths of the partially wet structures are larger than those of the
      corresponding dry structures with the same porosities. Subsequent gas diffusion
      simulations exploiting the mean-square displacement method indicate that while
      the effective diffusion coefficients significantly decrease in the presence of
      partially condensed liquids, they are larger than those in the dry structures
      with the same porosities. Moreover, we find that the ratio of the porosity to the
      tortuosity factor, which is a crucial parameter that determines an effective
      diffusion coefficient, can be reasonably related to the porosity even for the
      partially wet porous media.

PMID- 29347561
TI  - Irreversible thermodynamics of curved lipid membranes.
AB  - The theory of irreversible thermodynamics for arbitrarily curved lipid membranes
      is presented here. The coupling between elastic bending and irreversible
      processes such as intramembrane lipid flow, intramembrane phase transitions, and
      protein binding and diffusion is studied. The forms of the entropy production for
      the irreversible processes are obtained, and the corresponding thermodynamic
      forces and fluxes are identified. Employing the linear irreversible thermodynamic
      framework, the governing equations of motion along with appropriate boundary
      conditions are provided.

PMID- 29347562
TI  - Rational extended thermodynamics of a rarefied polyatomic gas with molecular
      relaxation processes.
AB  - We present a more refined version of rational extended thermodynamics of rarefied
      polyatomic gases in which molecular rotational and vibrational relaxation
      processes are treated individually. In this case, we need a triple hierarchy of
      the moment system and the system of balance equations is closed via the maximum
      entropy principle. Three different types of the production terms in the system,
      which are suggested by a generalized BGK-type collision term in the Boltzmann
      equation, are adopted. In particular, the rational extended thermodynamic theory
      with seven independent fields (ET_{7}) is analyzed in detail. Finally, the
      dispersion relation of ultrasonic wave derived from the ET_{7} theory is
      confirmed by the experimental data for CO_{2}, Cl_{2}, and Br_{2} gases.

PMID- 29347563
TI  - Importance of small-degree nodes in assortative networks with degree-weight
      correlations.
AB  - It has been known that assortative network structure plays an important role in
      spreading dynamics for unweighted networks. Yet its influence on weighted
      networks is not clear, in particular when weight is strongly correlated with the
      degrees of the nodes as we empirically observed in Twitter. Here we use the self
      consistent probability method and revised nonperturbative heterogenous mean-field
      theory method to investigate this influence on both susceptible-infective
      recovered (SIR) and susceptible-infective-susceptible (SIS) spreading dynamics.
      Both our simulation and theoretical results show that while the critical
      threshold is not significantly influenced by the assortativity, the prevalence in
      the supercritical regime shows a crossover under different degree-weight
      correlations. In particular, unlike the case of random mixing networks, in
      assortative networks, the negative degree-weight correlation leads to higher
      prevalence in their spreading beyond the critical transmissivity than that of the
      positively correlated. In addition, the previously observed inhibition effect on
      spreading velocity by assortative structure is not apparent in negatively degree
      weight correlated networks, while it is enhanced for that of the positively
      correlated. Detailed investigation into the degree distribution of the infected
      nodes reveals that small-degree nodes play essential roles in the supercritical
      phase of both SIR and SIS spreadings. Our results have direct implications in
      understanding viral information spreading over online social networks and
      epidemic spreading over contact networks.

PMID- 29347564
TI  - Epidemic spreading on activity-driven networks with attractiveness.
AB  - We study SIS epidemic spreading processes unfolding on a recent generalization of
      the activity-driven modeling framework. In this model of time-varying networks,
      each node is described by two variables: activity and attractiveness. The first
      describes the propensity to form connections, while the second defines the
      propensity to attract them. We derive analytically the epidemic threshold
      considering the time scale driving the evolution of contacts and the contagion as
      comparable. The solutions are general and hold for any joint distribution of
      activity and attractiveness. The theoretical picture is confirmed via large-scale
      numerical simulations performed considering heterogeneous distributions and
      different correlations between the two variables. We find that heterogeneous
      distributions of attractiveness alter the contagion process. In particular, in
      the case of uncorrelated and positive correlations between the two variables,
      heterogeneous attractiveness facilitates the spreading. On the contrary, negative
      correlations between activity and attractiveness hamper the spreading. The
      results presented contribute to the understanding of the dynamical properties of
      time-varying networks and their effects on contagion phenomena unfolding on their
      fabric.

PMID- 29347565
TI  - Formation and evolution of target patterns in Cahn-Hilliard flows.
AB  - We study the evolution of the concentration field in a single eddy in the two
      dimensional (2D) Cahn-Hilliard system to better understand scalar mixing
      processes in that system. This study extends investigations of the classic
      studies of flux expulsion in 2D magnetohydrodynamics and homogenization of
      potential vorticity in 2D fluids. Simulation results show that there are three
      stages in the evolution: (A) formation of a "jelly roll" pattern, for which the
      concentration field is constant along spirals; (B) a change in isoconcentration
      contour topology; and (C) formation of a target pattern, for which the
      isoconcentration contours follow concentric annuli. In the final target pattern
      stage, the isoconcentration bands align with stream lines. The results indicate
      that the target pattern is a metastable state. The band merger process continues
      on a time scale exponentially long relative to the eddy turnover time. The band
      merger process resembles step merger in drift-ZF staircases; this is
      characteristic of the long-time evolution of phase-separated patterns described
      by the Cahn-Hilliard equation.

PMID- 29347566
TI  - Macroscopic phase-resetting curves for spiking neural networks.
AB  - The study of brain rhythms is an open-ended, and challenging, subject of interest
      in neuroscience. One of the best tools for the understanding of oscillations at
      the single neuron level is the phase-resetting curve (PRC). Synchronization in
      networks of neurons, effects of noise on the rhythms, effects of transient
      stimuli on the ongoing rhythmic activity, and many other features can be
      understood by the PRC. However, most macroscopic brain rhythms are generated by
      large populations of neurons, and so far it has been unclear how the PRC
      formulation can be extended to these more common rhythms. In this paper, we
      describe a framework to determine a macroscopic PRC (mPRC) for a network of
      spiking excitatory and inhibitory neurons that generate a macroscopic rhythm. We
      take advantage of a thermodynamic approach combined with a reduction method to
      simplify the network description to a small number of ordinary differential
      equations. From this simplified but exact reduction, we can compute the mPRC via
      the standard adjoint method. Our theoretical findings are illustrated with and
      supported by numerical simulations of the full spiking network. Notably our mPRC
      framework allows us to predict the difference between effects of transient inputs
      to the excitatory versus the inhibitory neurons in the network.

PMID- 29347567
TI  - Kinetics of biochemical sensing by single cells and populations of cells.
AB  - We investigate the collective stationary sensing using N communicative cells,
      which involves surface receptors, diffusive signaling molecules, and cell-cell
      communication messengers. We restrict the scenarios to the signal-to-noise ratios
      (SNRs) for both strong communication and extrinsic noise only. We modified a
      previous model [Bialek and Setayeshgar, Proc. Natl. Acad. Sci. USA 102, 10040
      (2005)PNASA60027-842410.1073/pnas.0504321102] to eliminate the singularities in
      the fluctuation correlations by considering a uniform receptor distribution over
      the surface of each cell with a finite radius a. The modified model enables a
      simple and rigorous mathematical treatment of the collective sensing phenomenon.
      We then derive the scaling of the SNR for both juxtacrine and autocrine cases in
      all dimensions. For the optimal locations of the cells in the autocrine case, we
      find identical scaling for both two and three dimensions.

PMID- 29347568
TI  - Impact of environmental colored noise in single-species population dynamics.
AB  - Variability on external conditions has important consequences for the dynamics
      and the organization of biological systems. In many cases, the characteristic
      timescale of environmental changes as well as their correlations play a
      fundamental role in the way living systems adapt and respond to it. A proper
      mathematical approach to understand population dynamics, thus, requires
      approaches more refined than, e.g., simple white-noise approximations. To shed
      further light onto this problem, in this paper we propose a unifying framework
      based on different analytical and numerical tools available to deal with
      "colored" environmental noise. In particular, we employ a "unified colored noise
      approximation" to map the original problem into an effective one with white
      noise, and then we apply a standard path integral approach to gain analytical
      understanding. For the sake of specificity, we present our approach using as a
      guideline a variation of the contact process-which can also be seen as a birth
      death process of the Malthus-Verhulst class-where the propagation or birth rate
      varies stochastically in time. Our approach allows us to tackle in a systematic
      manner some of the relevant questions concerning population dynamics under
      environmental variability, such as determining the stationary population density,
      establishing the conditions under which a population may become extinct, and
      estimating extinction times. We focus on the emerging phase diagram and its
      possible phase transitions, underlying how these are affected by the presence of
      environmental noise time-correlations.

PMID- 29347569
TI  - Scaling of the surface vasculature on the human placenta.
AB  - The networks of veins and arteries on the chorionic plate of the human placenta
      are analyzed in terms of Voronoi cells derived from these networks. Two groups of
      placentas from the United States are studied: a population cohort with no
      prescreening, and a cohort from newborns with an elevated risk of developing
      autistic spectrum disorder. Scaled distributions of the Voronoi cell areas in the
      two cohorts collapse onto a single distribution, indicating common mechanisms for
      the formation of the complete vasculatures, but which have different levels of
      activity in the two cohorts.

PMID- 29347570
TI  - Flame propagation in two-dimensional solids: Particle-resolved studies with
      complex plasmas.
AB  - Using two-dimensional (2D) complex plasmas as an experimental model system,
      particle-resolved studies of flame propagation in classical 2D solids are carried
      out. Combining experiments, theory, and molecular dynamics simulations, we
      demonstrate that the mode-coupling instability operating in 2D complex plasmas
      reveals all essential features of combustion, such as an activated heat release,
      two-zone structure of the self-similar temperature profile ("flame front"), as
      well as thermal expansion of the medium and temperature saturation behind the
      front. The presented results are of relevance for various fields ranging from
      combustion and thermochemistry, to chemical physics and synthesis of materials.

PMID- 29347571
TI  - Diffusion dynamics and synchronizability of hierarchical products of networks.
AB  - The hierarchical product of networks represents a natural tool for building large
      networks out of two smaller subnetworks: a primary subnetwork and a secondary
      subnetwork. Here we study the dynamics of diffusion and synchronization processes
      on hierarchical products. We apply techniques previously used for approximating
      the eigenvalues of the adjacency matrix to the Laplacian matrix, allowing us to
      quantify the effects that the primary and secondary subnetworks have on diffusion
      and synchronization in terms of a coupling parameter that weighs the secondary
      subnetwork relative to the primary subnetwork. Diffusion processes are separated
      into two regimes: for small coupling the diffusion rate is determined by the
      structure of the secondary network, scaling with the coupling parameter, while
      for large coupling it is determined by the primary network and saturates.
      Synchronization, on the other hand, is separated into three regimes, for both
      small and large coupling hierarchical products have poor synchronization
      properties, but is optimized at an intermediate value. Moreover, the critical
      coupling value that optimizes synchronization is shaped by the relative
      connectivities of the primary and secondary subnetworks, compensating for
      significant differences between the two subnetworks.

PMID- 29347572
TI  - Multichain models of conserved lattice gas.
AB  - Conserved lattice-gas models in one dimension exhibit absorbing state phase
      transition (APT) with simple integer exponents beta=1=nu=eta, whereas the same on
      a ladder belong to directed percolation (DP) universality. We conjecture that
      additional stochasticity in particle transfer is a relevant perturbation and its
      presence on a ladder forces the APT to be in the DP class. To substantiate this
      we introduce a class of restricted conserved lattice-gas models on a multichain
      system (M*L square lattice with periodic boundary condition in both directions),
      where particles which have exactly one vacant neighbor are active and they move
      deterministically to the neighboring vacant site. We show that for odd number of
      chains, in the thermodynamic limit L->infinity, these models exhibit APT at
      rho_{c}=1/2(1+1/M) with beta=1. On the other hand, for even-chain systems
      transition occurs at rho_{c}=1/2 with beta=1,2 for M=2,4, respectively, and
      beta=3 for M>=6. We illustrate this unusual critical behavior analytically using
      a transfer-matrix method.

PMID- 29347573
TI  - Tricriticality in crossed Ising chains.
AB  - We explore the phase diagram of Ising spins on one-dimensional chains that criss
      cross in two perpendicular directions and that are connected by interchain
      couplings. This system is of interest as a simpler, classical analog of a quantum
      Hamiltonian that has been proposed as a model of magnetic behavior in
      Nb_{12}O_{29} and also, conceptually, as a geometry that is intermediate between
      one and two dimensions. Using mean-field theory as well as Metropolis Monte Carlo
      and Wang-Landau simulations, we locate quantitatively the boundaries of four
      ordered phases. Each becomes an effective Ising model with unique effective
      couplings at large interchain coupling. Away from this limit, we demonstrate
      nontrivial critical behavior, including tricritical points that separate first-
      and second-order phase transitions. Finally, we present evidence that this model
      belongs to the two-dimensional Ising universality class.

PMID- 29347574
TI  - Emergence of biaxial nematic phases in solutions of semiflexible dimers.
AB  - We investigate the isotropic, uniaxial nematic and biaxial nematic phases, and
      the transitions between them, for a model lyotropic mixture of flexible molecules
      consisting of two rigid rods connected by a spacer with variable bending
      stiffness. We apply density-functional theory within the Onsager approximation to
      describe strictly excluded-volume interactions in this athermal model and to self
      consistently find the orientational order parameters dictated by its complex
      symmetry, as functions of the density. Earlier work on lyotropic ordering of
      rigid bent-rod molecules is reproduced and extended to show explicitly the
      continuous phase transition at the Landau point, at a critical bend angle of
      36^{?}. For flexible dimers with no intrinsic biaxiality, we find that a biaxial
      nematic phase can nevertheless form at a sufficiently high density and low
      bending stiffness. For bending stiffness kappa>0.86k_{B}T, this biaxial phase
      manifests as dimer bending fluctuations occurring preferentially in one plane.
      When the dimers are more flexible, kappa<0.86k_{B}T, the modal shape of the
      fluctuating dimer is a V with an acute opening angle, and one of the biaxial
      order parameters changes sign, indicating a rotation of the directors. These two
      regions are separated by a narrow strip of uniaxial nematic in the phase diagram,
      which we generate in terms of the spacer stiffness and particle density.

PMID- 29347575
TI  - Critical phenomena of a hybrid phase transition in cluster merging dynamics.
AB  - Recently, a hybrid percolation transition (HPT) that exhibits both a
      discontinuous transition and critical behavior at the same transition point has
      been observed in diverse complex systems. While the HPT induced by avalanche
      dynamics has been studied extensively, the HPT induced by cluster merging
      dynamics (HPT-CMD) has received little attention. Here, we aim to develop a
      theoretical framework for the HPT-CMD. We find that two correlation-length
      exponents are necessary for characterizing the giant cluster and finite clusters
      separately. The conventional formula of the fractal dimension in terms of the
      critical exponents is not valid. Neither the giant nor finite clusters are
      fractals, but they have fractal boundaries. A finite-size scaling method for the
      HPT-CMD is also introduced.

PMID- 29347576
TI  - Multiscale Granger causality.
AB  - In the study of complex physical and biological systems represented by
      multivariate stochastic processes, an issue of great relevance is the description
      of the system dynamics spanning multiple temporal scales. While methods to assess
      the dynamic complexity of individual processes at different time scales are well
      established, multiscale analysis of directed interactions has never been
      formalized theoretically, and empirical evaluations are complicated by practical
      issues such as filtering and downsampling. Here we extend the very popular
      measure of Granger causality (GC), a prominent tool for assessing directed lagged
      interactions between joint processes, to quantify information transfer across
      multiple time scales. We show that the multiscale processing of a vector
      autoregressive (AR) process introduces a moving average (MA) component, and
      describe how to represent the resulting ARMA process using state space (SS)
      models and to combine the SS model parameters for computing exact GC values at
      arbitrarily large time scales. We exploit the theoretical formulation to identify
      peculiar features of multiscale GC in basic AR processes, and demonstrate with
      numerical simulations the much larger estimation accuracy of the SS approach
      compared to pure AR modeling of filtered and downsampled data. The improved
      computational reliability is exploited to disclose meaningful multiscale patterns
      of information transfer between global temperature and carbon dioxide
      concentration time series, both in paleoclimate and in recent years.

PMID- 29347577
TI  - Lognormal-like statistics of a stochastic squeeze process.
AB  - We analyze the full statistics of a stochastic squeeze process. The model's two
      parameters are the bare stretching rate w and the angular diffusion coefficient
      D. We carry out an exact analysis to determine the drift and the diffusion
      coefficient of log(r), where r is the radial coordinate. The results go beyond
      the heuristic lognormal description that is implied by the central limit theorem.
      Contrary to the common "quantum Zeno" approximation, the radial diffusion is not
      simply D_{r}=(1/8)w^{2}/D but has a nonmonotonic dependence on w/D. Furthermore,
      the calculation of the radial moments is dominated by the far non-Gaussian tails
      of the log(r) distribution.

PMID- 29347578
TI  - Turbulent flow over craters on Mars: Vorticity dynamics reveal aeolian excavation
      mechanism.
AB  - Impact craters are scattered across Mars. These craters exhibit geometric self
      similarity over a spectrum of diameters, ranging from tens to thousands of
      kilometers. The late Noachian-early Hesperian boundary marks a dramatic shift in
      the role of mid-latitude craters, from depocenter sedimentary basins to aeolian
      source areas. At present day, many craters contain prominent layered sedimentary
      mounds with maximum elevations comparable to the rim height. The mounds are
      remnants of Noachian deposition and are surrounded by a radial moat. Large-eddy
      simulation has been used to model turbulent flows over synthetic craterlike
      geometries. Geometric attributes of the craters and the aloft flow have been
      carefully matched to resemble ambient conditions in the atmospheric boundary
      layer of Mars. Vorticity dynamics analysis within the crater basin reveals the
      presence of counterrotating helical vortices, verifying the efficacy of
      deflationary models put forth recently by Bennett and Bell [K. Bennett and J.
      Bell, Icarus 264, 331 (2016)]ICRSA50019-103510.1016/j.icarus.2015.09.041 and Day
      et al. [M. Day et al., Geophys. Res. Lett. 43, 2473 (2016)]GPRLAJ0094
      827610.1002/2016GL068011. We show how these helical counterrotating vortices
      spiral around the outer rim, gradually deflating the moat and carving the mound;
      excavation occurs faster on the upwind side, explaining the radial eccentricity
      of the mounds relative to the surrounding crater basin.

PMID- 29347579
TI  - Electrostatic fluctuations in collisional plasmas.
AB  - We present a theory of electrostatic fluctuations in two-component plasmas where
      electrons and ions are described by Maxwellian distribution functions at unequal
      temperatures. Based on the exact solution of the Landau kinetic equation, that
      includes electron-electron, electron-ion, and ion-ion collision integrals, the
      dynamic form factor, S(k[over ?],omega), is derived for weakly coupled plasmas.
      The collective plasma responses at ion-acoustic, Langmuir, and entropy mode
      resonances are described for arbitrary wave numbers and frequencies in the entire
      range of plasma collisionality. The collisionless limit of S(k[over ?],omega) and
      the strong-collision result based on the fluctuation-dissipation theorem and
      classical transport at T_{e}=T_{i} are recovered and discussed. Results of
      several Thomson scattering experiments in the broad range of plasma parameters
      are described and discussed by means of our theory for S(k[over ?],omega).

PMID- 29347580
TI  - Kinetic approach to condensation: Diatomic gases with dipolar molecules.
AB  - We derive a kinetic equation for rarefied diatomic gases whose molecules have a
      permanent dipole moment. Estimating typical parameters of such gases, we show
      that quantum effects cannot be neglected when describing the rotation of
      molecules, which we thus approximate by quantum rotators. The intermolecular
      potential is assumed to involve an unspecified short-range repulsive component
      and a long-range dipole-dipole Coulomb interaction. In the kinetic equation
      derived, the former and the latter give rise, respectively, to the collision
      integral and a self-consistent electric field generated collectively by the
      dipoles (as in the Vlasov model of plasma). It turns out that the characteristic
      period of the molecules' rotation is much shorter than the time scale of the
      collective electric force and the latter is much shorter than the time scale of
      the collision integral, which allows us to average the kinetic equation over
      rotation. In the averaged model, collisions and interaction with the collective
      field affect only those rotational levels of the molecules that satisfy certain
      conditions of synchronism. It is then shown that the derived model does not
      describe condensation; i.e., permanent dipoles of molecules cannot exert the
      level of intermolecular attraction necessary for condensation. It is argued that
      an adequate model of condensation must include the temporary dipoles that
      molecules induce on each other during interaction, and that this model must be
      quantum, not classical.

PMID- 29347581
TI  - Noisy independent component analysis of autocorrelated components.
AB  - We present a method for the separation of superimposed, independent,
      autocorrelated components from noisy multichannel measurement. The presented
      method simultaneously reconstructs and separates the components, taking all
      channels into account, and thereby increases the effective signal-to-noise ratio
      considerably, allowing separations even in the high-noise regime. Characteristics
      of the measurement instruments can be included, allowing for application in
      complex measurement situations. Independent posterior samples can be provided,
      permitting error estimates on all desired quantities. Using the concept of
      information field theory, the algorithm is not restricted to any dimensionality
      of the underlying space or discretization scheme thereof.

PMID- 29347582
TI  - Estimation of the degree of dynamical instability from the information entropy of
      symbolic dynamics.
AB  - A positive Lyapunov exponent is the most convincing signature of chaos. However,
      existing methods for estimating the Lyapunov exponent from a time series often
      give unreliable estimates because they trace the time evolution of the distance
      between a pair of initially neighboring trajectories in phase space. Here, we
      propose a mathematical method for estimating the degree of dynamical instability,
      as a surrogate for the Lyapunov exponent, without tracing initially neighboring
      trajectories on the basis of the information entropy from a symbolic time series.
      We apply the proposed method to numerical time series generated by well-known
      chaotic systems and experimental time series and verify its validity.

PMID- 29347583
TI  - Quantum Monte Carlo with variable spins: Fixed-phase and fixed-node
      approximations.
AB  - We study several aspects of the recently introduced fixed-phase spinor diffusion
      Monte Carlo method, in particular, its relation to the fixed-node method and its
      potential use as a general approach for electronic structure calculations. We
      illustrate constructions of spinor-based wave functions with the full space-spin
      symmetry without assigning up or down spin labels to particular electrons,
      effectively "complexifying" even ordinary real-valued wave functions for
      Hamiltonians without spin terms. Interestingly, with proper choice of the
      simulation parameters and spin variables, such fixed-phase calculations enable
      one to reach also the fixed-node limit. The fixed-phase approximation has several
      desirable properties when compared to the fixed-node approximation. The fixed
      phase solution provides a straightforward interpretation as the lowest bosonic
      state in a given effective potential generated by the many-body approximate
      phase, whereas nodal boundary conditions are defined through less intuitive and
      complicated hypersurfaces with one dimension less than the original configuration
      space. In addition, the divergences of the local energy and drift at real wave
      function nodes are smoothed out to lower dimensionality when the wave function is
      complexified, thus decreasing the variation of sampled quantities and eliminating
      artificial nodal domain issues that can occur in the fixed-node formalism. We
      illustrate some of these properties on calculations of selected first-row systems
      that recover the fixed-node results with quantitatively similar levels of the
      corresponding biases. At the same time, the fixed-phase approach opens new
      possibilities for more general trial wave functions with further opportunities
      for increasing accuracy in practical calculations.

PMID- 29347584
TI  - Crossover from ballistic to normal heat transport in the phi^{4} lattice: If
      nonconservation of momentum is the reason, what is the mechanism?
AB  - Anomalous (non-Fourier) heat transport is no longer just a theoretical issue
      since it has been observed experimentally in a number of low-dimensional
      nanomaterials, such as SiGe nanowires, carbon nanotubes, and others. To
      understand these anomalous behaviors, exploring the microscopic origin of normal
      (Fourier) heat transport is a fascinating theoretical topic. However, this issue
      has not yet been fully understood even for one-dimensional (1D) model chains, in
      spite of a great amount of thorough studies done to date. From those studies, it
      has been widely accepted that the conservation of momentum is a key ingredient to
      induce anomalous heat transport, while momentum-nonconserving systems usually
      support normal heat transport where Fourier's law is valid. But if the
      nonconservation of momentum is the reason, what is the underlying microscopic
      mechanism for the observed normal heat transport? Here we carefully revisit a
      typical 1D momentum-nonconserving phi^{4} model, and we present evidence that the
      mobile discrete breathers, or, in other words, the moving intrinsic localized
      modes with frequency components above the linear phonon band, can be responsible
      for that.

PMID- 29347585
TI  - Reconstruction of a digital core containing clay minerals based on a clustering
      algorithm.
AB  - It is difficult to obtain a core sample and information for digital core
      reconstruction of mature sandstone reservoirs around the world, especially for an
      unconsolidated sandstone reservoir. Meanwhile, reconstruction and division of
      clay minerals play a vital role in the reconstruction of the digital cores,
      although the two-dimensional data-based reconstruction methods are specifically
      applicable as the microstructure reservoir simulation methods for the sandstone
      reservoir. However, reconstruction of clay minerals is still challenging from a
      research viewpoint for the better reconstruction of various clay minerals in the
      digital cores. In the present work, the content of clay minerals was considered
      on the basis of two-dimensional information about the reservoir. After
      application of the hybrid method, and compared with the model reconstructed by
      the process-based method, the digital core containing clay clusters without the
      labels of the clusters' number, size, and texture were the output. The statistics
      and geometry of the reconstruction model were similar to the reference model. In
      addition, the Hoshen-Kopelman algorithm was used to label various connected
      unclassified clay clusters in the initial model and then the number and size of
      clay clusters were recorded. At the same time, the K-means clustering algorithm
      was applied to divide the labeled, large connecting clusters into smaller
      clusters on the basis of difference in the clusters' characteristics. According
      to the clay minerals' characteristics, such as types, textures, and
      distributions, the digital core containing clay minerals was reconstructed by
      means of the clustering algorithm and the clay clusters' structure judgment. The
      distributions and textures of the clay minerals of the digital core were
      reasonable. The clustering algorithm improved the digital core reconstruction and
      provided an alternative method for the simulation of different clay minerals in
      the digital cores.

PMID- 29347586
TI  - Bak-Tang-Wiesenfeld model in the upper critical dimension: Induced criticality in
      lower-dimensional subsystems.
AB  - We present extensive numerical simulations of Bak-Tang-Wiesenfeld (BTW) sandpile
      model on the hypercubic lattice in the upper critical dimension D_{u}=4. After re
      extracting the critical exponents of avalanches, we concentrate on the three- and
      two-dimensional (2D) cross sections seeking for the induced criticality which are
      reflected in the geometrical and local exponents. Various features of finite-size
      scaling (FSS) theory have been tested and confirmed for all dimensions. The
      hyperscaling relations between the exponents of the distribution functions and
      the fractal dimensions are shown to be valid for all dimensions. We found that
      the exponent of the distribution function of avalanche mass is the same for the d
      dimensional cross sections and the d-dimensional BTW model for d=2 and 3. The
      geometrical quantities, however, have completely different behaviors with respect
      to the same-dimensional BTW model. By analyzing the FSS theory for the
      geometrical exponents of the two-dimensional cross sections, we propose that the
      2D induced models have degrees of similarity with the Gaussian free field (GFF).
      Although some local exponents are slightly different, this similarity is
      excellent for the fractal dimensions. The most important one showing this feature
      is the fractal dimension of loops d_{f}, which is found to be 1.50+/
      0.02~3/2=d_{f}^{GFF}.

PMID- 29347587
TI  - Spectral estimation of the percolation transition in clustered networks.
AB  - There have been several spectral bounds for the percolation transition in
      networks, using spectrum of matrices associated with the network such as the
      adjacency matrix and the nonbacktracking matrix. However, they are far from being
      tight when the network is sparse and displays clustering or transitivity, which
      is represented by existence of short loops, e.g., triangles. In this paper, for
      the bond percolation, we first propose a message-passing algorithm for
      calculating size of percolating clusters considering effects of triangles, then
      relate the percolation transition to the leading eigenvalue of a matrix that we
      name the triangle-nonbacktracking matrix, by analyzing stability of the message
      passing equations. We establish that our method gives a tighter lower bound to
      the bond percolation transition than previous spectral bounds, and it becomes
      exact for an infinite network with no loops longer than 3. We evaluate
      numerically our methods on synthetic and real-world networks, and discuss further
      generalizations of our approach to include higher-order substructures.

PMID- 29347588
TI  - Finite-size effects in canonical and grand-canonical quantum Monte Carlo
      simulations for fermions.
AB  - We introduce a quantum Monte Carlo method at finite temperature for interacting
      fermionic models in the canonical ensemble, where the conservation of the
      particle number is enforced. Although general thermodynamic arguments ensure the
      equivalence of the canonical and the grand-canonical ensembles in the
      thermodynamic limit, their approach to the infinite-volume limit is distinctively
      different. Observables computed in the canonical ensemble generically display a
      finite-size correction proportional to the inverse volume, whereas in the grand
      canonical ensemble the approach is exponential in the ratio of the linear size
      over the correlation length. We verify these predictions by quantum Monte Carlo
      simulations of the Hubbard model in one and two dimensions in the grand-canonical
      and the canonical ensemble. We prove an exact formula for the finite-size part of
      the free energy density, energy density and other observables in the canonical
      ensemble and relate this correction to a susceptibility computed in the
      corresponding grand-canonical ensemble. This result is confirmed by an exact
      computation of the one-dimensional classical Ising model in the canonical
      ensemble, which for classical models corresponds to the so-called fixed
      magnetization ensemble. Our method is useful for simulating finite systems which
      are not coupled to a particle bath, such as in nuclear or cold atom physics.

PMID- 29347589
TI  - Synchronization scenarios in the Winfree model of coupled oscillators.
AB  - Fifty years ago Arthur Winfree proposed a deeply influential mean-field model for
      the collective synchronization of large populations of phase oscillators. Here we
      provide a detailed analysis of the model for some special, analytically tractable
      cases. Adopting the thermodynamic limit, we derive an ordinary differential
      equation that exactly describes the temporal evolution of the macroscopic
      variables in the Ott-Antonsen invariant manifold. The low-dimensional model is
      then thoroughly investigated for a variety of pulse types and sinusoidal phase
      response curves (PRCs). Two structurally different synchronization scenarios are
      found, which are linked via the mutation of a Bogdanov-Takens point. From our
      results, we infer a general rule of thumb relating pulse shape and PRC offset
      with each scenario. Finally, we compare the exact synchronization threshold with
      the prediction of the averaging approximation given by the Kuramoto-Sakaguchi
      model. At the leading order, the discrepancy appears to behave as an odd function
      of the PRC offset.

PMID- 29347590
TI  - Emergent Levy behavior in single-cell stochastic gene expression.
AB  - Single-cell gene expression is inherently stochastic; its emergent behavior can
      be defined in terms of the chemical master equation describing the evolution of
      the mRNA and protein copy numbers as the latter tends to infinity. We establish
      two types of "macroscopic limits": the Kurtz limit is consistent with the
      classical chemical kinetics, while the Levy limit provides a theoretical
      foundation for an empirical equation proposed in N. Friedman et al., Phys. Rev.
      Lett. 97, 168302 (2006)PRLTAO0031-900710.1103/PhysRevLett.97.168302. Furthermore,
      we clarify the biochemical implications and ranges of applicability for various
      macroscopic limits and calculate a comprehensive analytic expression for the
      protein concentration distribution in autoregulatory gene networks. The
      relationship between our work and modern population genetics is discussed.

PMID- 29347591
TI  - Reconstruction of three-dimensional porous media using generative adversarial
      neural networks.
AB  - To evaluate the variability of multiphase flow properties of porous media at the
      pore scale, it is necessary to acquire a number of representative samples of the
      void-solid structure. While modern x-ray computer tomography has made it possible
      to extract three-dimensional images of the pore space, assessment of the
      variability in the inherent material properties is often experimentally not
      feasible. We present a method to reconstruct the solid-void structure of porous
      media by applying a generative neural network that allows an implicit description
      of the probability distribution represented by three-dimensional image data sets.
      We show, by using an adversarial learning approach for neural networks, that this
      method of unsupervised learning is able to generate representative samples of
      porous media that honor their statistics. We successfully compare measures of
      pore morphology, such as the Euler characteristic, two-point statistics, and
      directional single-phase permeability of synthetic realizations with the
      calculated properties of a bead pack, Berea sandstone, and Ketton limestone.
      Results show that generative adversarial networks can be used to reconstruct high
      resolution three-dimensional images of porous media at different scales that are
      representative of the morphology of the images used to train the neural network.
      The fully convolutional nature of the trained neural network allows the
      generation of large samples while maintaining computational efficiency. Compared
      to classical stochastic methods of image reconstruction, the implicit
      representation of the learned data distribution can be stored and reused to
      generate multiple realizations of the pore structure very rapidly.

PMID- 29347592
TI  - Diffusion, subdiffusion, and localization of active colloids in random post
      lattices.
AB  - Combining experiments and theory, we address the dynamics of self-propelled
      particles in crowded environments. We first demonstrate that motile colloids
      cruising at constant speed through random lattices undergo a smooth transition
      from diffusive to subdiffusive to localized dynamics upon increasing the obstacle
      density. We then elucidate the nature of these transitions by performing
      extensive simulations constructed from a detailed analysis of the colloid
      obstacle interactions. We evidence that repulsion at a distance and hard-core
      interactions both contribute to slowing down the long-time diffusion of the
      colloids. In contrast, the localization transition stems solely from excluded
      volume interactions and occurs at the void-percolation threshold. Within this
      critical scenario, equivalent to that of the random Lorentz gas, genuine
      asymptotic subdiffusion is found only at the critical density where the motile
      particles explore a fractal maze.

PMID- 29347593
TI  - Phase behavior and bulk structural properties of a microphase former with
      anisotropic competing interactions: A density functional theory study.
AB  - Using classical density functional theory, we investigate systems exhibiting
      interactions where a short-range anisotropic attractive force competes with a
      long-range spherically symmetric repulsive force. The former is modelled within
      Wertheim's first-order perturbation theory for patchy particles, and the
      repulsive part is assumed to be a Yukawa potential which is taken into account
      via a mean-field approximation. From previous studies of systems with spherically
      symmetric competing interactions, it is well known that such systems can exhibit
      stable bulk cluster phases (microphase separation) provided that the repulsion is
      sufficiently weak compared to the attraction. For the present model system, we
      find rich phase diagrams including both reentrant clustering and liquid-gas
      binodals. In particular, the model predicts inhomogeneous bulk phases at
      extremely low packing fractions, which cannot be observed in systems with
      isotropic competing interactions.

PMID- 29347594
TI  - Cell-size distribution and scaling in a one-dimensional Kolmogorov-Johnson-Mehl
      Avrami lattice model with continuous nucleation.
AB  - The Kolmogorov-Johnson-Mehl-Avrami (KJMA) growth model is considered on a one
      dimensional (1D) lattice. Cells can grow with constant speed and continuously
      nucleate on the empty sites. We offer an alternative mean-field-like approach for
      describing theoretically the dynamics and derive an analytical cell-size
      distribution function. Our method reproduces the same scaling laws as the KJMA
      theory and has the advantage that it leads to a simple closed form for the cell
      size distribution function. It is shown that a Weibull distribution is
      appropriate for describing the final cell-size distribution. The results are
      discussed in comparison with Monte Carlo simulation data.

PMID- 29347595
TI  - Coupling-enhanced stochastic resonance.
AB  - Stochastic resonance is analyzed in an array of nonlinear spatially coupled
      subsystems. Analytic expressions for the different steady-state solutions, for
      the rates of transitions between them in the presence of noise, and for the
      response to a weak external periodic forcing are derived. It is shown that the
      presence of spatial degrees of freedom modifies considerably the mechanisms of
      transitions between states and is responsible for a marked sensitivity of the
      response on the coupling constant and on the system size.

PMID- 29347596
TI  - Generalized fractional diffusion equations for subdiffusion in arbitrarily
      growing domains.
AB  - The ubiquity of subdiffusive transport in physical and biological systems has led
      to intensive efforts to provide robust theoretical models for this phenomena.
      These models often involve fractional derivatives. The important physical
      extension of this work to processes occurring in growing materials has proven
      highly nontrivial. Here we derive evolution equations for modeling subdiffusive
      transport in a growing medium. The derivation is based on a continuous-time
      random walk. The concise formulation of these evolution equations requires the
      introduction of a new, comoving, fractional derivative. The implementation of the
      evolution equation is illustrated with a simple model of subdiffusing proteins in
      a growing membrane.

PMID- 29347597
TI  - General purpose graphics-processing-unit implementation of cosmological domain
      wall network evolution.
AB  - Topological defects unavoidably form at symmetry breaking phase transitions in
      the early universe. To probe the parameter space of theoretical models and set
      tighter experimental constraints (exploiting the recent advances in astrophysical
      observations), one requires more and more demanding simulations, and therefore
      more hardware resources and computation time. Improving the speed and efficiency
      of existing codes is essential. Here we present a general purpose graphics
      processing-unit implementation of the canonical Press-Ryden-Spergel algorithm for
      the evolution of cosmological domain wall networks. This is ported to the Open
      Computing Language standard, and as a consequence significant speedups are
      achieved both in two-dimensional (2D) and 3D simulations.

PMID- 29347598
TI  - Electric generation and ratcheted transport of contact-charged drops.
AB  - We describe a simple microfluidic system that enables the steady generation and
      efficient transport of aqueous drops using only a constant voltage input. Drop
      generation is achieved through an electrohydrodynamic dripping mechanism by which
      conductive drops grow and detach from a grounded nozzle in response to an
      electric field. The now-charged drops are transported down a ratcheted channel by
      contact charge electrophoresis powered by the same voltage input used for drop
      generation. We investigate how the drop size, generation frequency, and transport
      velocity depend on system parameters such as the liquid viscosity, interfacial
      tension, applied voltage, and channel dimensions. The observed trends are well
      explained by a series of scaling analyses that provide insight into the dominant
      physical mechanisms underlying drop generation and ratcheted transport. We
      identify the conditions necessary for achieving reliable operation and discuss
      the various modes of failure that can arise when these conditions are violated.
      Our results demonstrate that simple electric inputs can power increasingly
      complex droplet operations with potential opportunities for inexpensive and
      portable microfluidic systems.

PMID- 29347599
TI  - Energy decay in a tapped granular column: Can a one-dimensional toy model provide
      insight into fully three-dimensional systems?
AB  - The decay of energy within particulate media subjected to an impulse is an issue
      of significant scientific interest, but also one with numerous important
      practical applications. In this paper, we study the dynamics of a granular system
      exposed to energetic impulses in the form of discrete taps from a solid surface.
      By considering a one-dimensional toy system, we develop a simple theory, which
      successfully describes the energy decay within the system following exposure to
      an impulse. We then extend this theory so as to make it applicable also to more
      realistic, three-dimensional granular systems, assessing the validity of the
      model through direct comparison with discrete particle method simulations. The
      theoretical form presented possesses several notable consequences; in particular,
      it is demonstrated that for suitably large systems, effects due to the bounding
      walls may be entirely neglected. We also establish the existence of a threshold
      system size above which a granular bed may be considered fully three dimensional.

PMID- 29347600
TI  - Liquidlike sloshing dynamics of monodisperse granulate.
AB  - Analogies between fluid flows and granular flows are useful because they pave the
      way for continuum treatments of granular media. However, in practice it is
      impossible to predict under what experimental conditions the dynamics of fluids
      and granulates are qualitatively similar. In the case of unsteadily driven
      systems no such analogy is known. For example, in a partially filled container
      subject to horizontal oscillations liquids slosh, whereas granular media of
      complex particles exhibit large-scale convection rolls. We here show that smooth
      monodisperse steel spheres exhibit liquidlike sloshing dynamics. Our findings
      highlight the role of particle material and geometry for the dynamics and phase
      transitions of the system.

PMID- 29347601
TI  - Chaos-assisted tunneling in the presence of Anderson localization.
AB  - Tunneling between two classically disconnected regular regions can be strongly
      affected by the presence of a chaotic sea in between. This phenomenon, known as
      chaos-assisted tunneling, gives rise to large fluctuations of the tunneling rate.
      Here we study chaos-assisted tunneling in the presence of Anderson localization
      effects in the chaotic sea. Our results show that the standard tunneling rate
      distribution is strongly modified by localization, going from the Cauchy
      distribution in the ergodic regime to a log-normal distribution in the strongly
      localized case, for both a deterministic and a disordered model. We develop a
      single-parameter scaling description which accurately describes the numerical
      data. Several possible experimental implementations using cold atoms, photonic
      lattices, or microwave billiards are discussed.

PMID- 29347602
TI  - Control of accuracy in the Wang-Landau algorithm.
AB  - The Wang-Landau (WL) algorithm has been widely used for simulations in many areas
      of physics. Our analysis of the WL algorithm explains its properties and shows
      that the difference of the largest eigenvalue of the transition matrix in the
      energy space from unity can be used to control the accuracy of estimating the
      density of states. Analytic expressions for the matrix elements are given in the
      case of the one-dimensional Ising model. The proposed method is further confirmed
      by numerical results for the one-dimensional and two-dimensional Ising models and
      also the two-dimensional Potts model.

PMID- 29347603
TI  - Asymmetric noise-induced large fluctuations in coupled systems.
AB  - Networks of interacting, communicating subsystems are common in many fields, from
      ecology, biology, and epidemiology to engineering and robotics. In the presence
      of noise and uncertainty, interactions between the individual components can lead
      to unexpected complex system-wide behaviors. In this paper, we consider a generic
      model of two weakly coupled dynamical systems, and we show how noise in one part
      of the system is transmitted through the coupling interface. Working
      synergistically with the coupling, the noise on one system drives a large
      fluctuation in the other, even when there is no noise in the second system.
      Moreover, the large fluctuation happens while the first system exhibits only
      small random oscillations. Uncertainty effects are quantified by showing how
      characteristic time scales of noise-induced switching scale as a function of the
      coupling between the two coupled parts of the experiment. In addition, our
      results show that the probability of switching in the noise-free system scales
      inversely as the square of reduced noise intensity amplitude, rendering the
      virtual probability of switching an extremely rare event. Our results showing the
      interplay between transmitted noise and coupling are also confirmed through
      simulations, which agree quite well with analytic theory.

PMID- 29347604
TI  - Capillary fluctuations of surface steps: An atomistic simulation study for the
      model Cu(111) system.
AB  - Molecular dynamics (MD) simulations are employed to investigate the capillary
      fluctuations of steps on the surface of a model metal system. The fluctuation
      spectrum, characterized by the wave number (k) dependence of the mean squared
      capillary-wave amplitudes and associated relaxation times, is calculated for
      <110> and <112> steps on the {111} surface of elemental copper near the melting
      temperature of the classical potential model considered. Step stiffnesses are
      derived from the MD results, yielding values from the largest system sizes of
      (37+/-1)meV/A[over ] for the different line orientations, implying that the
      stiffness is isotropic within the statistical precision of the calculations. The
      fluctuation lifetimes are found to vary by approximately four orders of magnitude
      over the range of wave numbers investigated, displaying a k dependence consistent
      with kinetics governed by step-edge mediated diffusion. The values for step
      stiffness derived from these simulations are compared to step free energies for
      the same system and temperature obtained in a recent MD-based thermodynamic
      integration (TI) study [Freitas, Frolov, and Asta, Phys. Rev. B 95, 155444
      (2017)2469-995010.1103/PhysRevB.95.155444]. Results from the capillary
      fluctuation analysis and TI calculations yield statistically significant
      differences that are discussed within the framework of statistical-mechanical
      theories for configurational contributions to step free energies.

PMID- 29347605
TI  - Classical many-particle systems with unique disordered ground states.
AB  - Classical ground states (global energy-minimizing configurations) of many
      particle systems are typically unique crystalline structures, implying zero
      enumeration entropy of distinct patterns (aside from trivial symmetry
      operations). By contrast, the few previously known disordered classical ground
      states of many-particle systems are all high-entropy (highly degenerate) states.
      Here we show computationally that our recently proposed "perfect-glass" many
      particle model [Sci. Rep. 6, 36963 (2016)10.1038/srep36963] possesses disordered
      classical ground states with a zero entropy: a highly counterintuitive situation
      . For all of the system sizes, parameters, and space dimensions that we have
      numerically investigated, the disordered ground states are unique such that they
      can always be superposed onto each other or their mirror image. At low energies,
      the density of states obtained from simulations matches those calculated from the
      harmonic approximation near a single ground state, further confirming ground
      state uniqueness. Our discovery provides singular examples in which entropy and
      disorder are at odds with one another. The zero-entropy ground states provide a
      unique perspective on the celebrated Kauzmann-entropy crisis in which the
      extrapolated entropy of a supercooled liquid drops below that of the crystal. We
      expect that our disordered unique patterns to be of value in fields beyond glass
      physics, including applications in cryptography as pseudorandom functions with
      tunable computational complexity.

PMID- 29347606
TI  - Coupling of link- and node-ordering in the coevolving voter model.
AB  - We consider the process of reaching the final state in the coevolving voter
      model. There is a coevolution of state dynamics, where a node can copy a state
      from a random neighbor with probabilty 1-p and link dynamics, where a node can
      rewire its link to another node of the same state with probability p. That
      exhibits an absorbing transition to a frozen phase above a critical value of
      rewiring probability. Our analytical and numerical studies show that in the
      active phase mean values of magnetization of nodes n and links m tend to the same
      value that depends on initial conditions. In a similar way mean degrees of spins
      up and spins down become equal. The system obeys a special statistical
      conservation law since a linear combination of both types magnetizations averaged
      over many realizations starting from the same initial conditions is a constant of
      motion: Lambda=(1-p)MUm(t)+pn(t)=const., where MU is the mean node degree. The
      final mean magnetization of nodes and links in the active phase is proportional
      to Lambda while the final density of active links is a square function of Lambda.
      If the rewiring probability is above a critical value and the system separates
      into disconnected domains, then the values of nodes and links magnetizations are
      not the same and final mean degrees of spins up and spins down can be different.

PMID- 29347607
TI  - Direct measurement of the ballistic motion of a freely floating colloid in
      Newtonian and viscoelastic fluids.
AB  - A thermal colloid suspended in a liquid will transition from a short-time
      ballistic motion to a long-time diffusive motion. However, the transition between
      ballistic and diffusive motion is highly dependent on the properties and
      structure of the particular liquid. We directly observe a free floating tracer
      particle's ballistic motion and its transition to the long-time regime in both a
      Newtonian fluid and a viscoelastic Maxwell fluid. We examine the motion of the
      free particle in a Newtonian fluid and demonstrate a high degree of agreement
      with the accepted Clercx-Schram model for motion in a dense fluid. Measurements
      of the functional form of the ballistic-to-diffusive transition provide direct
      measurements of the temperature, viscosity, and tracer radius. We likewise
      measure the motion in a viscoelastic Maxwell fluid and find a significant
      disagreement between the theoretical asymptotic behavior and our measured values
      of the microscopic properties of the fluid. We observe a greatly increased
      effective mass for a freely moving particle and a decreased plateau modulus.

PMID- 29347608
TI  - Mapping and discrimination of networks in the complexity-entropy plane.
AB  - Complex networks are usually characterized in terms of their topological,
      spatial, or information-theoretic properties and combinations of the associated
      metrics are used to discriminate networks into different classes or categories.
      However, even with the present variety of characteristics at hand it still
      remains a subject of current research to appropriately quantify a network's
      complexity and correspondingly discriminate between different types of complex
      networks, like infrastructure or social networks, on such a basis. Here we
      explore the possibility to classify complex networks by means of a statistical
      complexity measure that has formerly been successfully applied to distinguish
      different types of chaotic and stochastic time series. It is composed of a
      network's averaged per-node entropic measure characterizing the network's
      information content and the associated Jenson-Shannon divergence as a measure of
      disequilibrium. We study 29 real-world networks and show that networks of the
      same category tend to cluster in distinct areas of the resulting complexity
      entropy plane. We demonstrate that within our framework, connectome networks
      exhibit among the highest complexity while, e.g., transportation and
      infrastructure networks display significantly lower values. Furthermore, we
      demonstrate the utility of our framework by applying it to families of random
      scale-free and Watts-Strogatz model networks. We then show in a second
      application that the proposed framework is useful to objectively construct
      threshold-based networks, such as functional climate networks or recurrence
      networks, by choosing the threshold such that the statistical network complexity
      is maximized.

PMID- 29347609
TI  - Noise-induced drift in two-dimensional anisotropic systems.
AB  - We study the isothermal Brownian dynamics of a particle in a system with
      spatially varying diffusivity. Due to the heterogeneity of the system, the
      particle's mean displacement does not vanish even if it does not experience any
      physical force. This phenomenon has been termed "noise-induced drift," and has
      been extensively studied for one-dimensional systems. Here, we examine the noise
      induced drift in a two-dimensional anisotropic system, characterized by a
      symmetric diffusion tensor with unequal diagonal elements. A general expression
      for the mean displacement vector is derived and presented as a sum of two
      vectors, depicting two distinct drifting effects. The first vector describes the
      tendency of the particle to drift toward the high diffusivity side in each
      orthogonal principal diffusion direction. This is a generalization of the well
      known expression for the noise-induced drift in one-dimensional systems. The
      second vector represents a novel drifting effect, not found in one-dimensional
      systems, originating from the spatial rotation in the directions of the principal
      axes. The validity of the derived expressions is verified by using Langevin
      dynamics simulations. As a specific example, we consider the relative diffusion
      of two transmembrane proteins, and demonstrate that the average distance between
      them increases at a surprisingly fast rate of several tens of micrometers per
      second.

PMID- 29347610
TI  - Relaxation time of the global order parameter on multiplex networks: The role of
      interlayer coupling in Kuramoto oscillators.
AB  - This work considers the time scales associated with the global order parameter
      and the interlayer synchronization of coupled Kuramoto oscillators on
      multiplexes. For two-layer multiplexes with an initially high degree of
      synchronization in each layer, the difference between the average phases in each
      layer is analyzed from two different perspectives: the spectral analysis and the
      nonlinear Kuramoto model. Both viewpoints confirm that the prior time scales are
      inversely proportional to the interlayer coupling strength. Thus, increasing the
      interlayer coupling always shortens the transient regimes of both the global
      order parameter and the interlayer synchronization. Surprisingly, the analytical
      results show that the convergence of the global order parameter is faster than
      the interlayer synchronization, and the latter is generally faster than the
      global synchronization of the multiplex. The formalism also outlines the effects
      of frequencies on the difference between the average phases of each layer, and it
      identifies the conditions for an oscillatory behavior. Computer simulations are
      in fairly good agreement with the analytical findings, and they reveal that the
      time scale of the global order parameter is half the size of the time scale of
      the multiplex, if not smaller.

PMID- 29347611
TI  - Iterated function systems for DNA replication.
AB  - The kinetic equations of DNA replication are shown to be exactly solved in terms
      of iterated function systems, running along the template sequence and giving the
      statistical properties of the copy sequences, as well as the kinetic and
      thermodynamic properties of the replication process. With this method, different
      effects due to sequence heterogeneity can be studied, in particular, a transition
      between linear and sublinear growths in time of the copies, and a transition
      between continuous and fractal distributions of the local velocities of the DNA
      polymerase along the template. The method is applied to the human mitochondrial
      DNA polymerase gamma without and with exonuclease proofreading.

PMID- 29347612
TI  - Biological cell as a soft magnetoelectric material: Elucidating the physical
      mechanisms underpinning the detection of magnetic fields by animals.
AB  - Sharks, birds, bats, turtles, and many other animals can detect magnetic fields.
      Aside from using this remarkable ability to exploit the terrestrial magnetic
      field map to sense direction, a subset is also able to implement a version of the
      so-called geophysical positioning system. How do these animals detect magnetic
      fields? The answer to this rather deceptively simple question has proven to be
      quite elusive. The currently prevalent theories, while providing interesting
      insights, fall short of explaining several aspects of magnetoreception. For
      example, minute magnetic particles have been detected in magnetically sensitive
      animals. However, how is the detected magnetic field converted into electrical
      signals given any lack of experimental evidence for relevant electroreceptors? In
      principle, a magnetoelectric material is capable of converting magnetic signals
      into electricity (and vice versa). This property, however, is rare and restricted
      to a rather small set of exotic hard crystalline materials. Indeed, such elements
      have never been detected in the animals studied so far. In this work we
      quantitatively outline the conditions under which a biological cell may detect a
      magnetic field and convert it into electrical signals detectable by biological
      cells. Specifically, we prove the existence of an overlooked strain-mediated
      mechanism and show that most biological cells can act as nontrivial
      magnetoelectric materials provided that the magnetic permeability constant is
      only slightly more than that of a vacuum. The enhanced magnetic permeability is
      easily achieved by small amounts of magnetic particles that have been
      experimentally detected in magnetosensitive animals. Our proposed mechanism
      appears to explain most of the experimental observations related to the physical
      basis of magnetoreception.

PMID- 29347613
TI  - Test of the diffusing-diffusivity mechanism using near-wall colloidal dynamics.
AB  - The mechanism of diffusing diffusivity predicts that, in environments where the
      diffusivity changes gradually, the displacement distribution becomes non
      Gaussian, even though the mean-square displacement grows linearly with time.
      Here, we report single-particle tracking measurements of the diffusion of
      colloidal spheres near a planar substrate. Because the local effective
      diffusivity is known, we have been able to carry out a direct test of this
      mechanism for diffusion in inhomogeneous media.

PMID- 29347614
TI  - Analysis of crackling noise using the maximum-likelihood method: Power-law mixing
      and exponential damping.
AB  - Crackling noise can be initiated by competing or coexisting mechanisms. These
      mechanisms can combine to generate an approximate scale invariant distribution
      that contains two or more contributions. The overall distribution function can be
      analyzed, to a good approximation, using maximum-likelihood methods and assuming
      that it follows a power law although with nonuniversal exponents depending on a
      varying lower cutoff. We propose that such distributions are rather common and
      originate from a simple superposition of crackling noise distributions or
      exponential damping.

PMID- 29347615
TI  - Publisher's Note: Critical and Griffiths-McCoy singularities in quantum Ising
      spin glasses on d-dimensional hypercubic lattices: A series expansion study
      [Phys. Rev. E 96, 022139 (2017)].
AB  - This corrects the article DOI: 10.1103/PhysRevE.96.022139.

PMID- 29347616
TI  - Design and investigation of de Vries liquid crystals based on 5-phenyl-pyrimidine
      and (R,R)-2,3-epoxyhexoxy backbone.
AB  - Calamitic liquid crystals based on 5-phenyl-pyrimidine derivatives have been
      designed, synthesized, and characterized. The 5-phenyl pyrimidine core was
      functionalized with a chiral (R,R)-2,3-epoxyhexoxy chain on one side and either
      siloxane or perfluoro terminated chains on the opposite side. The one involving a
      perfluorinated chain shows SmA^{*} phase over a wide temperature range of 82 
      degrees C, whereas the siloxane analog exhibits both SmA^{*} and SmC^{*} phases
      over a broad range of temperatures, and a weak first-order SmA^{*}-SmC^{*}
      transition is observed. For the siloxane analog, the reduction factor for the
      layer shrinkage R (relative to its thickness at the SmA^{*}-SmC^{*} transition
      temperature, T_{AC}) is ~0.373, and layer shrinkage is 1.7% at a temperature of
      13  degrees C below the T_{AC}. This compound is considered to have "de Vries
      smectic" characteristics with the de Vries coefficient C_{deVries} of ~0.86 on
      the scale of zero (maximum-layer shrinkage) to 1 (zero-layer shrinkage). A three
      parameter mean-field model is introduced for the orientational distribution
      function (ODF) to reproduce the electro-optic properties. This model explains the
      experimental results and leads to the ODF, which exhibits a crossover from the
      sugar-loaf to diffuse-cone ODF some 3  degrees C above T_{AC}.

PMID- 29347617
TI  - Force percolation transition of jammed granular systems.
AB  - The mechanical and transport properties of jammed materials originate from an
      underlying percolating network of contact forces between the grains. Using
      extensive simulations we investigate the force-percolation transition of this
      network, where two particles are considered as linked if their interparticle
      force overcomes a threshold. We show that this transition belongs to the random
      percolation universality class, thus ruling out the existence of long-range
      correlations between the forces. Through a combined size and pressure scaling for
      the percolative quantities, we show that the continuous force percolation
      transition evolves into the discontinuous jamming transition in the zero pressure
      limit, as the size of the critical region scales with the pressure.

PMID- 29347618
TI  - Universality of oscillating boiling in Leidenfrost transition.
AB  - The Leidenfrost transition leads a boiling system to the boiling crisis, a state
      in which the liquid loses contact with the heated surface due to excessive vapor
      generation. Here, using experiments of liquid droplets boiling on a heated
      surface, we report a phenomenon, termed oscillating boiling, at the Leidenfrost
      transition. We show that oscillating boiling results from the competition between
      two effects: separation of liquid from the heated surface due to localized
      boiling and rewetting. We argue theoretically that the Leidenfrost transition can
      be predicted based on its link with the oscillating boiling phenomenon and verify
      the prediction experimentally for various liquids.

PMID- 29347619
TI  - Topological defects in an unconfined nematic fluid induced by single and double
      spherical colloidal particles.
AB  - We present numerical solutions to the Landau-de Gennes free-energy model under
      the one-constant approximation for systems of single and double spherical
      colloidal particles immersed in an otherwise uniformly aligned nematic liquid
      crystal. A perfect homeotropic surface anchoring of liquid-crystal molecules on
      the spherical surface is considered. A large parameter space is carefully
      examined, including those in the free-energy model and those describing the dimer
      configurations and the background liquid-crystal orientation. The stability of
      the resulting liquid-crystal defects appearing in the neighborhood of the
      colloidal dimer pair is analyzed in light of the numerical results for their free
      energies. A number of scenarios are considered: a free dimer pair in a nematic
      fluid where the free-energy ground states are described in terms of a phase
      diagram, and a constrained dimer pair where the interparticle distance and the
      relative orientation of the distance vector to the nematic director can be
      manipulated. We pay particular attention to the nonsymmetric solutions, which
      yield several metastable defect states that can be observed in real systems. The
      high-precision numerical calculations are based on a spectral method, which is an
      enabling factor that allows us to compare the subtle difference in the free
      energies of different defect structures.

PMID- 29347620
TI  - Suppression of crystalline fluctuations by competing structures in a supercooled
      liquid.
AB  - We propose a geometrical characterization of amorphous liquid structures that
      suppress crystallization by competing locally with crystalline order. We
      introduce for this purpose the crystal affinity of a liquid, a simple measure of
      its propensity to accumulate local crystalline structures on cooling. This
      quantity is explicitly related to the high-temperature structural covariance
      between local fluctuations in crystal order and that of competing liquid
      structures: favoring a structure that, due to poor overlap properties,
      anticorrelates with crystalline order reduces the affinity of the liquid. Using a
      lattice model of a liquid, we show that this quantity successfully predicts the
      tendency of a liquid to either accumulate or suppress local crystalline
      fluctuations with increasing supercooling. We demonstrate that the crystal
      affinity correlates strongly with the crystal nucleation rate and the crystal
      liquid interfacial free energy of the low-temperature liquid, making our theory a
      predictive tool to determine which amorphous structures enhance glass-forming
      ability.

PMID- 29347621
TI  - Transient anomalous diffusion regimes in reversible adsorbing systems.
AB  - A solvable, minimal model of diffusion in the presence of a reversible adsorption
      site is investigated. We show that the diffusive particles are influenced by the
      adsorbing site on transient times when they have anomalous subdiffusive behavior.
      However, the particle dispersion law crosses over to the normal diffusive regime
      on asymptotically long times. The subdiffusive regime is characterized by a
      t^{1/4} transient scaling with the same exponent as for the irreversible
      adsorption. On this transient time scale dominated by particle adsorption, there
      is a depletion of particles near the adsorbing site, and the typical width of the
      depletion zone grows in time as t^{1/4} with the same exponent as the
      subdiffusive dispersion. We show that having a nonzero desorption probability for
      the adsorbed particles produces a crossover towards normal diffusion on time
      scales larger than a characteristic reactive time, which we show scales with
      diffusivity and the adsorption site reactivity.

PMID- 29347622
TI  - Transport regimes spanning magnetization-coupling phase space.
AB  - The manner in which transport properties vary over the entire parameter-space of
      coupling and magnetization strength is explored. Four regimes are identified
      based on the relative size of the gyroradius compared to other fundamental length
      scales: the collision mean free path, Debye length, distance of closest approach,
      and interparticle spacing. Molecular dynamics simulations of self-diffusion and
      temperature anisotropy relaxation spanning the parameter space are found to agree
      well with the predicted boundaries. Comparison with existing theories reveals
      regimes where they succeed, where they fail, and where no theory has yet been
      developed.

PMID- 29347623
TI  - Origin of the inertial deviation from Darcy's law: An investigation from a
      microscopic flow analysis on two-dimensional model structures.
AB  - Inertial flow in porous media occurs in many situations of practical relevance
      among which one can cite flows in column reactors, in filters, in aquifers, or
      near wells for hydrocarbon recovery. It is characterized by a deviation from
      Darcy's law that leads to a nonlinear relationship between the pressure drop and
      the filtration velocity. In this work, this deviation, also known as the
      nonlinear, inertial, correction to Darcy's law, which is subject to controversy
      upon its origin and dependence on the filtration velocity, is studied through
      numerical simulations. First, the microscopic flow problem was solved
      computationally for a wide range of Reynolds numbers up to the limit of steady
      flow within ordered and disordered porous structures. In a second step, the
      macroscopic characteristics of the porous medium and flow (permeability and
      inertial correction tensors) that appear in the macroscale model were computed.
      From these results, different flow regimes were identified: (1) the weak inertia
      regime where the inertial correction has a cubic dependence on the filtration
      velocity and (2) the strong inertia (Forchheimer) regime where the inertial
      correction depends on the square of the filtration velocity. However, the
      existence and origin of those regimes, which depend also on the microstructure
      and flow orientation, are still not well understood in terms of their physical
      interpretations, as many causes have been conjectured in the literature. In the
      present study, we provide an in-depth analysis of the flow structure to identify
      the origin of the deviation from Darcy's law. For accuracy and clarity purposes,
      this is carried out on two-dimensional structures. Unlike the previous studies
      reported in the literature, where the origin of inertial effects is often
      identified on a heuristic basis, a theoretical justification is presented in this
      work. Indeed, a decomposition of the convective inertial term into two components
      is carried out formally allowing the identification of a correlation between the
      flow structure and the different inertial regimes. These components correspond to
      the curvature of the flow streamlines weighted by the local fluid kinetic energy
      on the one hand and the distribution of the kinetic energy along these lines on
      the other hand. In addition, the role of the recirculation zones in the
      occurrence and in the form of the deviation from Darcy's law was thoroughly
      analyzed. For the porous structures under consideration, it is shown that (1) the
      kinetic energy lost in the vortices is insignificant even at high filtration
      velocities and (2) the shape of the flow streamlines induced by the recirculation
      zones plays an important role in the variation of the flow structure, which is
      correlated itself to the different flow regimes.

PMID- 29347624
TI  - Non-Poisson renewal events and memory.
AB  - We study two different forms of fluctuation-dissipation processes generating
      anomalous relaxations to equilibrium of an initial out-of-equilibrium condition,
      the former being based on a stationary although very slow correlation function
      and the latter characterized by the occurrence of crucial events, namely, non
      Poisson renewal events, incompatible with the stationary condition. Both forms of
      regression to equilibrium have the same nonexponential Mittag-Leffler structure.
      We analyze the single trajectories of the two processes by recording the time
      distances between two consecutive origin recrossings and establishing the
      corresponding waiting time probability density function (PDF), psi(t). In the
      former case, with no crucial events, psi(t) is an exponential, and in the latter
      case, with crucial events, psi(t) is an inverse power law PDF with a diverging
      first moment. We discuss the consequences that this result is expected to have
      for the correct interpretation of some anomalous relaxation processes.

PMID- 29347625
TI  - Modeling of the interaction of an x-ray free-electron laser with large finite
      samples.
AB  - We describe a model for the study of the interaction of short x-ray free-electron
      laser (XFEL) pulses with large finite samples. Hydrodynamics is solved in one
      dimensional planar geometry with consideration of the electron-ion energy
      exchange and of the possible elastoplastic behavior. From a time-dependent
      calculation of the complex refractive index and of the underlying atomic physics,
      XFEL energy deposition is modeled through a calculation of the radiation field in
      the material. In the case of hard x-ray irradiation, energetic electrons induced
      by the XFEL absorption can propagate and deposit their energy outside the
      interaction region. Simulations of the interaction of hard x-ray ultrashort
      pulses with solid materials Ru and Si at different grazing incidence angles are
      presented and discussed. The results obtained demonstrate the potential of this
      approach to predict damage dynamics for materials of interest for x-ray optics.

PMID- 29347626
TI  - Langevin equation elucidates the mechanism of the Rayleigh-Benard instability by
      coupling molecular motions and macroscopic fluctuations.
AB  - It is well known that Brownian motion can be described using Langevin equation.
      In this paper we extend the application of the Langevin equation to the Rayleigh
      Benard (RB) flow, assuming that each molecule in the system is a Brownian
      particle colliding with its surrounding molecules. The phenomenon of thermal
      instability, changing from a conductive to a convective state, is well reproduced
      by Langevin dynamics simulations. The roles of the drag force and the random
      force terms in the Langevin equation in triggering thermal instability are
      elucidated via numerical tests. Furthermore, we demonstrate that the strength of
      the fluctuation correlations increases as the Rayleigh number approaches the
      critical value, and the characteristics of the fluctuation correlations below the
      onset of instability foreshadow the form of the convective patterns emerging
      above the critical point. The Langevin equation, together with the form of the
      fluctuation correlations, sheds new light on the mechanism of the RB instability.

PMID- 29347627
TI  - Static and dynamic properties of two-dimensional Coulomb clusters.
AB  - We study the temperature dependence of static and dynamic responses of Coulomb
      interacting particles in two-dimensional confinements across the crossover from
      solid- to liquid-like behaviors. While static correlations that investigate the
      translational and bond orientational order in the confinements show the
      footprints of hexatic-like phase at low temperatures, dynamics of the particles
      slow down considerably in this phase, reminiscent of a supercooled liquid. Using
      density correlations, we probe long-lived heterogeneities arising from the
      interplay of the irregularity in the confinement and long-range Coulomb
      interactions. The relaxation at multiple time scales show stretched-exponential
      decay of spatial correlations in irregular traps. Temperature dependence of
      characteristic time scales, depicting the structural relaxation of the system,
      show striking similarities with those observed for the glassy systems, indicating
      that some of the key signatures of supercooled liquids emerge in confinements
      with lower spatial symmetries.

PMID- 29347628
TI  - Opposing effects of cationic antimicrobial peptides and divalent cations on
      bacterial lipopolysaccharides.
AB  - The permeability of the bacterial outer membrane, enclosing Gram-negative
      bacteria, depends on the interactions of the outer, lipopolysaccharide (LPS)
      layer, with surrounding ions and molecules. We present a coarse-grained model for
      describing how cationic amphiphilic molecules (e.g., antimicrobial peptides)
      interact with and perturb the LPS layer in a biologically relevant medium,
      containing monovalent and divalent salt ions (e.g., Mg^{2+}). In our approach,
      peptide binding is driven by electrostatic and hydrophobic interactions and is
      assumed to expand the LPS layer, eventually priming it for disruption. Our
      results suggest that in parameter ranges of biological relevance (e.g., at
      micromolar concentrations) the antimicrobial peptide magainin 2 effectively
      disrupts the LPS layer, even though it has to compete with Mg^{2+} for the layer.
      They also show how the integrity of LPS is restored with an increasing
      concentration of Mg^{2+}. Using the approach, we make a number of predictions
      relevant for optimizing peptide parameters against Gram-negative bacteria and for
      understanding bacterial strategies to develop resistance against cationic
      peptides.

PMID- 29347629
TI  - Perturbative dynamics of open quantum systems by renormalization group method.
AB  - We analyze perturbative dynamics of a composite system consisting of a quantum
      mechanical system and an environment by the renormalization group (RG) method.
      The solution obtained from the RG method has no secular terms and approximates
      the exact solution for a long time interval. Moreover, the RG method causes a
      reduction of the dynamics of the composite system under some assumptions. We show
      that this reduced dynamics is closely related to a quantum master equation for
      the quantum mechanical system. We compare this dynamics with the exact dynamics
      in an exactly solvable spin-boson model.

PMID- 29347630
TI  - Temperature measurement of hohlraum radiation for energy loss experiments in
      indirectly laser heated carbon plasma.
AB  - For ion energy loss measurements in plasmas with near solid densities, an
      indirect laser heating scheme for carbon foils has been developed at GSI
      Helmholtzzentrum fur Schwerionenforschung GmbH (Darmstadt, Germany). To achieve
      an electron density of 10^{22}cm^{3} and an electron temperature of 10-30eV, two
      carbon foils with an areal density of 100MUg/cm^{2} heated in a double-hohlraum
      configuration have been chosen. In this paper we present the results of
      temperature measurements of both primary and secondary hohlraums for two
      different hohlraum designs. They were heated by the PHELIX laser with a
      wavelength of 527nm and an energy of 150J in 1.5ns. For this purpose the
      temperature has been investigated by an x-ray streak camera with a transmission
      grating as the dispersive element.

PMID- 29347631
TI  - Phase transitions in restricted Boltzmann machines with generic priors.
AB  - We study generalized restricted Boltzmann machines with generic priors for units
      and weights, interpolating between Boolean and Gaussian variables. We present a
      complete analysis of the replica symmetric phase diagram of these systems, which
      can be regarded as generalized Hopfield models. We underline the role of the
      retrieval phase for both inference and learning processes and we show that
      retrieval is robust for a large class of weight and unit priors, beyond the
      standard Hopfield scenario. Furthermore, we show how the paramagnetic phase
      boundary is directly related to the optimal size of the training set necessary
      for good generalization in a teacher-student scenario of unsupervised learning.

PMID- 29347632
TI  - Dynamics of a thermally driven film climbing the outside of a vertical cylinder.
AB  - The dynamics of a film climbing the outside of a vertical cylinder under the
      competing effects of a thermally driven surface tension gradient and gravity is
      examined through numerical simulations of a thin-film model for the film height.
      The model, including boundary conditions, depends on three parameters, the scaled
      cylinder radius R[over ], the upstream film height h_{infinity}, and the
      downstream precursor film thickness b, and reduces to the model for Marangoni
      driven film climbing a vertical plate in the limit R[over ]->infinity. The
      axisymmetric advancing front displays dynamics similar to that found along a
      vertical plate where, depending on h_{infinity}, the film forms a single Lax
      shock, an undercompressive double shock, or a rarefaction-undercompressive shock.
      A linear stability analysis of the Lax shock reveals the number of fingers that
      form along the contact line increases linearly with cylinder circumference while
      no fingers form for sufficiently small cylinders (below R[over ]~1.15 when
      b=0.1). The substrate curvature controls the height of the Lax shock, bounds on
      h_{infinity} that define the three distinct solutions, and the maximum growth
      rate of contact line perturbations to the Lax shock when R[over ]=O(1), whereas
      the three solutions and the stability of the Lax shock converge to the behavior
      one observes on a vertical plate when R[over ]>=O(10). An energy analysis reveals
      that the azimuthal curvatures of the base state and perturbation, which arise
      from the annular geometry of the film, promote instability of the advancing
      contact line.

PMID- 29347633
TI  - Stochastic thermodynamics of interacting degrees of freedom: Fluctuation theorems
      for detached path probabilities.
AB  - Systems with interacting degrees of freedom play a prominent role in stochastic
      thermodynamics. Our aim is to use the concept of detached path probabilities and
      detached entropy production for bipartite Markov processes and elaborate on a
      series of special cases including measurement-feedback systems, sensors, and
      hidden Markov models. For these special cases we show that fluctuation theorems
      involving the detached entropy production recover known results which have been
      obtained separately before. Additionally, we show that the fluctuation relation
      for the detached entropy production can be used in model selection for data
      stemming from a hidden Markov model. We discuss the relation to previous
      approaches including those which use information flow or learning rate to
      quantify the influence of one subsystem on the other. In conclusion, we present a
      complete framework with which to find fluctuation relations for coupled systems.

PMID- 29347634
TI  - Strong diffusion formulation of Markov chain ensembles and its optimal weaker
      reductions.
AB  - : Two self-contained diffusion formulations, in the form of coupled stochastic
      differential equations, are developed for the temporal evolution of state
      densities over an ensemble of Markov chains evolving independently under a common
      transition rate matrix. Our first formulation derives from Kurtz's strong
      approximation theorem of density-dependent Markov jump processes [Stoch. PROCESS:
      Their Appl. 6, 223 (1978)STOPB70304-414910.1016/0304-4149(78)90020-0] and,
      therefore, strongly converges with an error bound of the order of lnN/N for
      ensemble size N. The second formulation eliminates some fluctuation variables,
      and correspondingly some noise terms, within the governing equations of the
      strong formulation, with the objective of achieving a simpler analytic
      formulation and a faster computation algorithm when the transition rates are
      constant or slowly varying. There, the reduction of the structural complexity is
      optimal in the sense that the elimination of any given set of variables takes
      place with the lowest attainable increase in the error bound. The resultant
      formulations are supported by numerical simulations.

PMID- 29347635
TI  - Classifying Potts critical lines.
AB  - We use scale invariant scattering theory to exactly determine the lines of
      renormalization group fixed points invariant under the permutational symmetry
      S_{q} in two dimensions, and we show how one of these scattering solutions
      describes the ferromagnetic and square lattice antiferromagnetic critical lines
      of the q-state Potts model. Other solutions we determine should correspond to new
      critical lines. In particular, we obtain that a S_{q}-invariant fixed point can
      be found up to the maximal value q=(7+sqrt[17])/2. This is larger than the
      usually assumed maximal value 4 and leaves room for a second-order
      antiferromagnetic transition at q=5.

PMID- 29347636
TI  - Glassy swirls of active dumbbells.
AB  - Is an active glass different from a conventional passive glass? To address this,
      we study the dynamics of a dense binary mixture of soft dumbbells, each subject
      to an active propulsion force and thermal fluctuations. This dense assembly shows
      dynamical arrest, first to a translational and then to a rotational glass, as one
      reduces temperature T or the self-propulsion force f. We monitor the dynamics
      along an iso-relaxation-time contour in the (T-f) plane. We find dramatic
      differences both in the fragility and in the nature of dynamical heterogeneity,
      which characterize the onset of glass formation-the activity-induced glass
      exhibits large swirls or vortices, whose scale is set by activity, and it appears
      to diverge as one approaches the glass transition. This large collective swirling
      movement should have implications for collective cell migration in epithelial
      layers. We construct continuum hydrodynamic equations for the simulated system,
      and we show that the observed behavior of this growing dynamic length scale can
      be understood from these equations.

PMID- 29347637
TI  - Ideal radiation source for plasma spectroscopy generated by laser ablation.
AB  - Laboratory plasmas inherently exhibit temperature and density gradients leading
      to complex investigations. We show that plasmas generated by laser ablation can
      constitute a robust exception to this. Supported by emission features not
      observed with other sources, we achieve plasmas of various compositions which are
      both uniform and in local thermodynamic equilibrium. These properties
      characterize an ideal radiation source opening multiple perspectives in plasma
      spectroscopy. The finding also constitutes a breakthrough in the analytical field
      as fast analyses of complex materials become possible.

PMID- 29347638
TI  - Effects of group velocity and multiplasmon resonances on the modulation of
      Langmuir waves in a degenerate plasma.
AB  - We study the nonlinear wave modulation of Langmuir waves (LWs) in a fully
      degenerate plasma. Using the Wigner-Moyal equation coupled to the Poisson
      equation and the multiple scale expansion technique, a modified nonlocal
      nonlinear Schrodinger (NLS) equation is derived which governs the evolution of LW
      envelopes in degenerate plasmas. The nonlocal nonlinearity in the NLS equation
      appears due to the group velocity and multiplasmon resonances, i.e., resonances
      induced by the simultaneous particle absorption of multiple wave quanta. We focus
      on the regime where the resonant velocity of electrons is larger than the Fermi
      velocity and thereby the linear Landau damping is forbidden. As a result, the
      nonlinear wave-particle resonances due to the group velocity and multiplasmon
      processes are the dominant mechanisms for wave-particle interaction. It is found
      that in contrast to classical or semiclassical plasmas, the group velocity
      resonance does not necessarily give rise the wave damping in the strong quantum
      regime where hk~mv_{F} with h denoting the reduced Planck's constant, m the
      electron mass, and v_{F} the Fermi velocity; however, the three-plasmon process
      plays a dominant role in the nonlinear Landau damping of wave envelopes. In this
      regime, the decay rate of the wave amplitude is also found to be higher compared
      to that in the modest quantum regime where the multiplasmon effects are
      forbidden.

PMID- 29347639
TI  - Experimental realization of a minimal microscopic heat engine.
AB  - Microscopic heat engines are microscale systems that convert energy flows between
      heat reservoirs into work or systematic motion. We have experimentally realized a
      minimal microscopic heat engine. It consists of a colloidal Brownian particle
      optically trapped in an elliptical potential well and simultaneously coupled to
      two heat baths at different temperatures acting along perpendicular directions.
      For a generic arrangement of the principal directions of the baths and the
      potential, the symmetry of the system is broken, such that the heat flow drives a
      systematic gyrating motion of the particle around the potential minimum. Using
      the experimentally measured trajectories, we quantify the gyrating motion of the
      particle, the resulting torque that it exerts on the potential, and the
      associated heat flow between the heat baths. We find excellent agreement between
      the experimental results and the theoretical predictions.

PMID- 29347640
TI  - Thermodynamic cost for classical counterdiabatic driving.
AB  - Motivated by the recent growing interest about the thermodynamic cost of
      shortcuts to adiabaticity, we consider the cost of driving a classical system by
      the so-called counterdiabatic driving (CD). To do so, we proceed in three steps:
      first we review a general definition recently put forward in the literature for
      the thermodynamic cost of driving a Hamiltonian system; then we provide a new
      complementary definition of cost, which is of particular relevance for cases
      where the average excess work vanishes; finally, we apply our general framework
      to the case of CD. Interestingly, we find that in such a case our results are the
      exact classical counterparts of those reported by Funo et al. [Phys. Rev. Lett.
      118, 100602 (2017)PRLTAO0031-900710.1103/PhysRevLett.118.100602]. In particular
      we show that a universal trade-off between speed and cost for CD also exists in
      the classical case. To illustrate our points we consider the example of a time
      dependent harmonic oscillator subject to different strategies of adiabatic
      control.

PMID- 29347641
TI  - Sound-mediated stable configurations for polystyrene particles.
AB  - Here we report an experimental observation of the self-organization effect of
      polystyrene particles formed by acoustically induced interaction forces. Two
      types of stable configurations are observed experimentally: one is mechanically
      equilibrium and featured by nonzero interparticle separations, and the other
      corresponds to a closely packed assembly, which is created by strong attractions
      among the aggregated particles. For the former case involving two or three
      particles, the most probable interparticle separations (counted for numerous
      independent initial arrangements) agree well with the theoretical predictions.
      For the latter case, the number of the final stable configurations grows with the
      particle number, and the occurrence probability of each configuration is
      interpreted by a simple geometric model.

PMID- 29347642
TI  - Carpet cloak for water waves.
AB  - Cloaking is a challenging topic in the field of wave motion, and is of
      significant theoretical value. In this article, a type of carpet cloak has been
      theoretically designed for water waves by using the effective medium and
      transformation theory. This carpet cloak device, created by a three-dimensional
      printer, is composed of a periodic structure which realizes the equivalent
      anisotropic water depth. We demonstrate its excellent cloaking performance
      numerically and experimentally in a wide range of frequencies and angles of
      incidence, with low wave attenuation characteristics and simple device
      realization of this carpet cloak illustrating that water wave transformation is a
      powerful method with which to manipulate water waves.

PMID- 29347643
TI  - Nonhelical turbulence and the inverse transfer of energy: A parameter study.
AB  - We explore the phenomenon of the recently discovered inverse transfer of energy
      from small to large scales in decaying magnetohydrodynamical turbulence by
      Brandenburg et al. [Phys. Rev. Lett. 114, 075001 (2015)PRLTAO0031
      900710.1103/PhysRevLett.114.075001], even for nonhelical magnetic fields. For
      this investigation we mainly employ the Pencil Code performing a parameter study,
      where we vary the Prandtl number, the kinematic viscosity, and the initial
      spectrum. We find that to get a decay that exhibits this inverse transfer, large
      Reynolds numbers (O~10^{3}) are needed and low Prandtl numbers of the order unity
      Pr=1 are preferred. Compared to helical MHD turbulence, though, the inverse
      transfer is much less efficient in transferring magnetic energy to larger scales
      than the well-known effect of the inverse cascade. Hence, applying the inverse
      transfer to the magnetic field evolution in the Early Universe, we question
      whether the nonhelical inverse transfer is effective enough to explain the
      observed void magnetic fields if a magnetogenesis scenario during the electroweak
      phase transition is assumed.

PMID- 29347644
TI  - Adiabatic cooling processes in frustrated magnetic systems with pyrochlore
      structure.
AB  - We investigate in detail the process of adiabatic cooling in the framework of the
      exactly solvable antiferromagnetic spin-1/2 Ising model in the presence of the
      external magnetic field on an approximate lattice with pyrochlore structure. The
      behavior of the entropy of the model is studied and exact values of the residual
      entropies of all ground states are found. The temperature variation of the system
      under adiabatic (de)magnetization is investigated and the central role of the
      macroscopically degenerated ground states in cooling processes is explicitly
      demonstrated. It is shown that the model parameter space of the studied
      geometrically frustrated system is divided into five disjunct regions with
      qualitatively different processes of the adiabatic cooling. The effectiveness of
      the adiabatic (de)magnetization cooling in the studied model is compared to the
      corresponding processes in paramagnetic salts. It is shown that the processes of
      the adiabatic cooling in the antiferromagnetic frustrated systems are much more
      effective especially in nonzero external magnetic fields. It means that the
      frustrated magnetic materials with pyrochlore structure can be considered as very
      promising refrigerants mainly in the situations with nonzero final values of the
      magnetic field.

PMID- 29347645
TI  - Geometry and the onset of rigidity in a disordered network.
AB  - Disordered spring networks that are undercoordinated may abruptly rigidify when
      sufficient strain is applied. Since the deformation in response to applied strain
      does not change the generic quantifiers of network architecture, the number of
      nodes and the number of bonds between them, this rigidity transition must have a
      geometric origin. Naive, degree-of-freedom-based mechanical analyses such as the
      Maxwell-Calladine count or the pebble game algorithm overlook such geometric
      rigidity transitions and offer no means of predicting or characterizing them. We
      apply tools that were developed for the topological analysis of zero modes and
      states of self-stress on regular lattices to two-dimensional random spring
      networks and demonstrate that the onset of rigidity, at a finite simple shear
      strain gamma^{?}, coincides with the appearance of a single state of self-stress,
      accompanied by a single floppy mode. The process conserves the topologically
      invariant difference between the number of zero modes and the number of states of
      self-stress but imparts a finite shear modulus to the spring network. Beyond the
      critical shear, the network acquires a highly anisotropic elastic modulus,
      resisting further deformation most strongly in the direction of the rigidifying
      shear. We confirm previously reported critical scaling of the corresponding
      differential shear modulus. In the subcritical regime, a singular value
      decomposition of the network's compatibility matrix foreshadows the onset of
      rigidity by way of a continuously vanishing singular value corresponding to the
      nascent state of self-stress.

PMID- 29347646
TI  - Marangoni effect on small-amplitude capillary waves in viscous fluids.
AB  - We derive a general integro-differential equation for the transient behavior of
      small-amplitude capillary waves on the planar surface of a viscous fluid in the
      presence of the Marangoni effect. The equation is solved for an insoluble
      surfactant solution in concentration below the critical micelle concentration
      undergoing convective-diffusive surface transport. The special case of a
      diffusion-driven surfactant is considered near the the critical damping
      wavelength. The Marangoni effect is shown to contribute to the overall damping
      mechanism, and a first-order term correction to the critical wavelength with
      respect to the surfactant concentration difference and the Schmidt number is
      proposed.

PMID- 29347647
TI  - Fast and slow domino regimes in transient network dynamics.
AB  - It is well known that the addition of noise to a multistable dynamical system can
      induce random transitions from one stable state to another. For low noise, the
      times between transitions have an exponential tail and Kramers' formula gives an
      expression for the mean escape time in the asymptotic limit. If a number of
      multistable systems are coupled into a network structure, a transition at one
      site may change the transition properties at other sites. We study the case of
      escape from a "quiescent" attractor to an "active" attractor in which transitions
      back can be ignored. There are qualitatively different regimes of transition,
      depending on coupling strength. For small coupling strengths, the transition
      rates are simply modified but the transitions remain stochastic. For large
      coupling strengths, transitions happen approximately in synchrony-we call this a
      "fast domino" regime. There is also an intermediate coupling regime where some
      transitions happen inexorably but with a delay that may be arbitrarily long-we
      call this a "slow domino" regime. We characterize these regimes in the low noise
      limit in terms of bifurcations of the potential landscape of a coupled system. We
      demonstrate the effect of the coupling on the distribution of timings and (in
      general) the sequences of escapes of the system.

PMID- 29347648
TI  - Nonreciprocal wave transmission through an extended discrete nonlinear
      Schrodinger dimer.
AB  - We analyze a one-dimensional extended discrete nonlinear Schrodinger (DNLS) dimer
      model for nonreciprocal wave transmission. The extension corresponds to the
      addition of a nonlocal or intersite nonlinear response in addition to a purely
      cubic local (on-site) nonlinear response, which refines the purely cubic model
      and aligns to more realistic situations. We observe that a diodelike action
      persists in the extended case; however, the inclusion of nonlocal response tends
      to reduce the diode action. We show that this extension results in achieving the
      diode effect at lower incoming intensities as compared to the purely cubic case.
      We also report that a nearly perfect diode action is possible in the extended
      case for a higher level of asymmetry between on-site potentials than its cubic
      counterpart. Moreover, we vary different site-dependent parameters to probe for
      regimes of a better diode effect within this extended model. We also present the
      corresponding stability analysis for the exact stationary solutions to the
      extended DNLS equation, we discuss the bifurcation behavior in detail, and we
      explicitly give the regions of stability.

PMID- 29347649
TI  - Pressure and flow of exponentially self-correlated active particles.
AB  - Microscopic swimming particles, which dissipate energy to execute persistent
      directed motion, are a classic example of a nonequilibrium system. We investigate
      the noninteracting Ornstein-Uhlenbeck Particle (OUP), which is propelled through
      a viscous medium by a force which is correlated over a finite time. We obtain an
      exact expression for the steady-state phase-space density of a single OUP
      confined by a quadratic potential, and use the result to explore more complex
      geometries, both through analytical approximations and numerical simulations. In
      a "Casimir"-style setup involving two narrowly spaced walls, we describe a
      particle-trapping phenomenon, which leads to a repulsive effective interaction
      between the walls, while in a two-dimensional annulus geometry, we observe net
      stresses which resemble the Laplace pressure.

PMID- 29347650
TI  - Kinetics and thermodynamics of a driven open quantum system.
AB  - Redfield theory provides a closed kinetic description of a quantum system in weak
      contact with a very dense reservoir. Landau-Zener theory does the same for a time
      dependent driven system in contact with a sparse reservoir. Using a simple model,
      we analyze the validity of these two theories by comparing their predictions with
      exact numerical results. We show that despite their a priori different range of
      validity, these two descriptions can give rise to an identical quantum master
      equation. Both theories can be used for a nonequilibrium thermodynamic
      description, which we show is consistent with exact thermodynamic identities
      evaluated in the full system-reservoir space. We emphasize the importance of
      properly accounting for the system-reservoir interaction energy and of operating
      in regimes where the reservoir can be considered as close to ideal.

PMID- 29347651
TI  - Nonlinear and subharmonic stability analysis in film-driven morphological
      patterns.
AB  - The interaction of a gravity-driven water film with an evolving solid substrate
      (calcite or ice) results in the formation of fascinating wavy patterns similar
      both in caves and in ice-falls. Due to their remarkable similarity, we adopt a
      unified approach in the study of pattern formation of longitudinally oriented
      organ-pipe-like structures, called flutings. Since the morphogenesis of cave
      patterns can evolve for millennia, they have an additional value as silent
      repositories of past climates. Fluting formation is studied with the aid of
      gradient expansion and center manifold projection. In particular, through
      gradient expansion, a Benney-type equation accounting for the movable boundary is
      obtained. The coupling with a wall evolution equation provides a morphodynamic
      model for fluting formation, explored through linear and nonlinear analyses. In
      this way, closed relationships for the selected wave number and for the finite
      amplitude are achieved. However, as finite-amplitude monochromatic waves may be
      destabilized by nonlinear interactions with other modes, we verify, through
      center manifold projection, the stability of the fundamental to subharmonic
      disturbances. Conclusively, we perform numerical simulations of the fully
      nonlinear equations to validate the theory results.

PMID- 29347652
TI  - Role of red cells and plasma composition on blood sessile droplet evaporation.
AB  - The morphology of dried blood droplets derives from the deposition of red cells,
      the main components of their solute phase. Up to now, evaporation-induced
      convective flows were supposed to be at the base of red cell distribution in
      blood samples. Here, we present a direct visualization by videomicroscopy of the
      internal dynamics in desiccating blood droplets, focusing on the role of cell
      concentration and plasma composition. We show that in diluted suspensions, the
      convection is promoted by the rich molecular composition of plasma, whereas it is
      replaced by an outward red blood cell displacement front at higher hematocrits.
      We also evaluate by ultrasounds the effect of red cell deposition on the temporal
      evolution of sample rigidity and adhesiveness.

PMID- 29347653
TI  - Stochastic thermodynamics of quantum maps with and without equilibrium.
AB  - We study stochastic thermodynamics for a quantum system of interest whose
      dynamics is described by a completely positive trace-preserving (CPTP) map as a
      result of its interaction with a thermal bath. We define CPTP maps with
      equilibrium as CPTP maps with an invariant state such that the entropy production
      due to the action of the map on the invariant state vanishes. Thermal maps are a
      subgroup of CPTP maps with equilibrium. In general, for CPTP maps, the
      thermodynamic quantities, such as the entropy production or work performed on the
      system, depend on the combined state of the system plus its environment. We show
      that these quantities can be written in terms of system properties for maps with
      equilibrium. The relations that we obtain are valid for arbitrary coupling
      strengths between the system and the thermal bath. The fluctuations of
      thermodynamic quantities are considered in the framework of a two-point
      measurement scheme. We derive the entropy production fluctuation theorem for
      general maps and a fluctuation relation for the stochastic work on a system that
      starts in the Gibbs state. Some simplifications for the probability distributions
      in the case of maps with equilibrium are presented. We illustrate our results by
      considering spin 1/2 systems under thermal maps, nonthermal maps with
      equilibrium, maps with nonequilibrium steady states, and concatenations of them.
      Finally, and as an important application, we consider a particular limit in which
      the concatenation of maps generates a continuous time evolution in Lindblad form
      for the system of interest, and we show that the concept of maps with and without
      equilibrium translates into Lindblad equations with and without quantum detailed
      balance, respectively. The consequences for the thermodynamic quantities in this
      limit are discussed.

PMID- 29347654
TI  - Time-dependent Tonks-Langmuir model is unstable.
AB  - We investigate a time-dependent extension of the Tonks-Langmuir model for a one
      dimensional plasma discharge with collisionless kinetic ions and Boltzmann
      electrons. Ions are created uniformly throughout the volume and flow from the
      center of the discharge to the boundary wall due to a self-consistent, zero-order
      electric field. Solving this model using a particle-in-cell simulation, we
      observe coherent low-frequency, long-wavelength unstable ion waves which move
      toward the boundary with a speed below both the ion acoustic speed and the
      average ion velocity. The maximum amplitude of the wave potential fluctuations
      peaks at ~0.09T_{e} near the wall, where T_{e} is the electron temperature in
      electron volts. Using linear kinetic theory, we identify this instability as slow
      ion-acoustic wave modes which are destabilized by the zero-order electric field.

PMID- 29347655
TI  - Emergence of chaos in a viscous solution of rods.
AB  - It is shown that the addition of small amounts of microscopic rods in a viscous
      fluid at low Reynolds number causes a significant increase of the flow
      resistance. Numerical simulations of the dynamics of the solution reveal that
      this phenomenon is associated to a transition from laminar to chaotic flow.
      Polymer stresses give rise to flow instabilities which, in turn, perturb the
      alignment of the rods. This coupled dynamics results in the activation of a wide
      range of scales, which enhances the mixing efficiency of viscous flows.

PMID- 29347656
TI  - Theory-based design of sintered granular composites triples three-phase boundary
      in fuel cells.
AB  - Solid-oxide fuel cells produce electric current from energy released by a
      spontaneous electrochemical reaction. The efficiency of these devices depends
      crucially on the microstructure of their electrodes and in particular on the
      three-phase boundary (TPB) length, along which the energy-producing reaction
      occurs. We present a systematic maximization of the TPB length as a function of
      four readily controllable microstructural parameters, for any given mean
      hydraulic radius, which is a conventional measure of the permeability to gas
      flow. We identify the maximizing parameters and show that the TPB length can be
      increased by a factor of over 300% compared to current common practices. We
      support this result by calculating the TPB of several numerically simulated
      structures. We also compare four models for a single intergranular contact in the
      sintered electrode and show that the model commonly used in the literature is
      oversimplified and unphysical. We then propose two alternatives.

PMID- 29347657
TI  - Mapping of the Bak, Tang, and Wiesenfeld sandpile model on a two-dimensional
      Ising-correlated percolation lattice to the two-dimensional self-avoiding random
      walk.
AB  - The self-organized criticality on the random fractal networks has many
      motivations, like the movement pattern of fluid in the porous media. In addition
      to the randomness, introducing correlation between the neighboring portions of
      the porous media has some nontrivial effects. In this paper, we consider the
      Ising-like interactions between the active sites as the simplest method to bring
      correlations in the porous media, and we investigate the statistics of the BTW
      model in it. These correlations are controlled by the artificial "temperature" T
      and the sign of the Ising coupling. Based on our numerical results, we propose
      that at the Ising critical temperature T_{c} the model is compatible with the
      universality class of two-dimensional (2D) self-avoiding walk (SAW). Especially
      the fractal dimension of the loops, which are defined as the external frontier of
      the avalanches, is very close to D_{f}^{SAW}=4/3. Also, the corresponding open
      curves has conformal invariance with the root-mean-square distance
      R_{rms}~t^{3/4} (t being the parametrization of the curve) in accordance with the
      2D SAW. In the finite-size study, we observe that at T=T_{c} the model has some
      aspects compatible with the 2D BTW model (e.g., the 1/log(L)-dependence of the
      exponents of the distribution functions) and some in accordance with the Ising
      model (e.g., the 1/L-dependence of the fractal dimensions). The finite-size
      scaling theory is tested and shown to be fulfilled for all statistical
      observables in T=T_{c}. In the off-critical temperatures in the close vicinity of
      T_{c} the exponents show some additional power-law behaviors in terms of T-T_{c}
      with some exponents that are reported in the text. The spanning cluster
      probability at the critical temperature also scales with L^{1/2}, which is
      different from the regular 2D BTW model.

PMID- 29347658
TI  - Finding multiple core-periphery pairs in networks.
AB  - With a core-periphery structure of networks, core nodes are densely
      interconnected, peripheral nodes are connected to core nodes to different
      extents, and peripheral nodes are sparsely interconnected. Core-periphery
      structure composed of a single core and periphery has been identified for various
      networks. However, analogous to the observation that many empirical networks are
      composed of densely interconnected groups of nodes, i.e., communities, a network
      may be better regarded as a collection of multiple cores and peripheries. We
      propose a scalable algorithm to detect multiple nonoverlapping groups of core
      periphery structure in a network. We illustrate our algorithm using synthesized
      and empirical networks. For example, we find distinct core-periphery pairs with
      different political leanings in a network of political blogs and separation
      between international and domestic subnetworks of airports in some single
      countries in a worldwide airport network.

PMID- 29347659
TI  - Crystallization of finite-extensible nonlinear elastic Lennard-Jones coarse
      grained polymers.
AB  - The ability of a simple coarse-grained finite-extensible nonlinear elastic (FENE)
      Lennard-Jones (LJ) polymer model to be crystallized is investigated by molecular
      dynamics simulations. The optimal FENE Lennard-Jones parameter combinations
      (ratio between FENE and LJ equilibrium distances) and the optimal lattice
      parameters are calculated for five different perfect crystallite structures:
      simple tetragonal, body-centered tetragonal, body-centered orthorhombic,
      hexagonal primitive, and hexagonal close packed. It was found that the most
      energetically favorable structure is the body-centered orthorhombic. Starting
      with an equilibrated polymer liquid and with the optimal parameters found for the
      body-centered orthorhombic, an isothermal treatment led to the formation of large
      lamellar crystallites with a typical chain topology: folded, loop, and tie
      chains, and with a crystallinity of about 60%-70%, similar to real
      semicrystalline polymers. This simple coarse-grained Lennard-Jones model provides
      a qualitative tool to study semicrystalline microstructures for polymers.

PMID- 29347660
TI  - Universal Gaussian behavior of driven lattice gases at short times.
AB  - The dynamic and static critical behaviors of driven and equilibrium lattice gas
      models are studied in two spatial dimensions. We show that in the short-time
      regime immediately following a critical quench, the dynamics of the transverse
      anisotropic order parameter, its autocorrelation, and Binder cumulant are
      consistent with the prediction of a Gaussian, i.e., noninteracting, effective
      theory, both for the nonequilibrium lattice gases and, to some extent, their
      equilibrium counterpart. Such a superuniversal behavior is observed only at short
      times after a critical quench, while the various models display their distinct
      behaviors in the stationary states, described by the corresponding, known
      universality classes.

PMID- 29347661
TI  - Activity-driven changes in the mechanical properties of fire ant aggregations.
AB  - Fire ant aggregations are active materials composed of individual constituents
      that are able to transform internal energy into work. We find using rheology and
      direct visualization that the aggregation undergoes activity cycles that affect
      the mechanical properties of the system. When the activity is high, the
      aggregation approximately equally stores and dissipates energy, it is more
      homogeneous, and exerts a high outward force. When the activity is low, the
      aggregation is predominantly elastic, it is more heterogeneous, and it exerts a
      small outward force. We rationalize our results using a simple kinetic model
      where the number of active ants within the aggregation is the essential quantity.

PMID- 29347662
TI  - Deciphering the kinetic structure of multi-ion plasma shocks.
AB  - Strong collisional shocks in multi-ion plasmas are featured in many high-energy
      density environments, including inertial confinement fusion implosions. However,
      their basic structure and its dependence on key parameters (e.g., the Mach number
      and the plasma ion composition) are poorly understood, and inconsistencies in
      that regard remain in the literature. In particular, the shock width's dependence
      on the Mach number has been hotly debated for decades. Using a high-fidelity
      Vlasov-Fokker-Planck code, iFP, and direct comparisons to multi-ion hydrodynamic
      simulations and semianalytic predictions, we resolve the structure of steady
      state planar shocks in D-^{3}He plasmas. Additionally, we derive and confirm with
      kinetic simulations a quantitative description of the dependence of the shock
      width on the Mach number and initial ion concentration.

PMID- 29347663
TI  - Magnetization plateau as a result of the uniform and gradual electron doping in a
      coupled spin-electron double-tetrahedral chain.
AB  - The double-tetrahedral chain in a longitudinal magnetic field, whose nodal
      lattice sites occupied by the localized Ising spins regularly alternate with
      triangular plaquettes with the dynamics described by the Hubbard model, is
      rigorously investigated. It is demonstrated that the uniform change of electron
      concentration controlled by the chemical potential in a combination with the
      competition between model parameters and the external magnetic field leads to the
      formation of one chiral and seven nonchiral phases at the absolute zero
      temperature. Rational plateaux at one-third and one-half of the saturation
      magnetization can also be identified in the low-temperature magnetization curves.
      On the other hand, the gradual electron doping results in 11 different ground
      state regions that distinguish from each other by the evolution of the electron
      distribution during this process. Several doping-dependent magnetization plateaux
      are observed in the magnetization process as a result of the continuous change of
      electron content in the model.

PMID- 29347664
TI  - Morphodynamics of a growing microbial colony driven by cell death.
AB  - Bacterial cells can often self-organize into multicellular structures with
      complex spatiotemporal morphology. In this work, we study the spatiotemporal
      dynamics of a growing microbial colony in the presence of cell death. We present
      an individual-based model of nonmotile bacterial cells which grow and proliferate
      by consuming diffusing nutrients on a semisolid two-dimensional surface. The
      colony spreads by growth forces and sliding motility of cells and undergoes cell
      death followed by subsequent disintegration of the dead cells in the medium. We
      model cell death by considering two possible situations: In one of the cases,
      cell death occurs in response to the limitation of local nutrients, while the
      other case corresponds to an active death process, known as apoptotic or
      programmed cell death. We demonstrate how the colony morphology is influenced by
      the presence of cell death. Our results show that cell death facilitates
      transitions from roughly circular to highly branched structures at the periphery
      of an expanding colony. Interestingly, our results also reveal that for the
      colonies which are growing in higher initial nutrient concentrations, cell death
      occurs much earlier compared to the colonies which are growing in lower initial
      nutrient concentrations. This work provides new insights into the branched
      patterning of growing bacterial colonies as a consequence of complex interplay
      among the biochemical and mechanical effects.

PMID- 29347665
TI  - Universal features of cluster numbers in percolation.
AB  - The number of clusters per site n(p) in percolation at the critical point p=p_{c}
      is not itself a universal quantity; it depends upon the lattice and percolation
      type (site or bond). However, many of its properties, including finite-size
      corrections, scaling behavior with p, and amplitude ratios, show various degrees
      of universal behavior. Some of these are universal in the sense that the behavior
      depends upon the shape of the system, but not lattice type. Here, we elucidate
      the various levels of universality for elements of n(p) both theoretically and by
      carrying out extensive studies on several two- and three-dimensional systems, by
      high-order series analysis, Monte Carlo simulation, and exact enumeration. We
      find many results, including precise values for n(p_{c}) for several systems, a
      clear demonstration of the singularity in n^{''}(p), and metric scale factors. We
      make use of the matching polynomial of Sykes and Essam to find exact relations
      between properties for lattices and matching lattices. We propose a criterion for
      an absolute metric factor b based upon the singular behavior of the scaling
      function, rather than a relative definition of the metric that has previously
      been used.

PMID- 29347666
TI  - Publisher's Note: Metal nanospheres under intense continuous-wave illumination: A
      unique case of nonperturbative nonlinear nanophotonics [Phys. Rev. E 96, 012212
      (2017)].
AB  - This corrects the article DOI: 10.1103/PhysRevE.96.012212.

PMID- 29347667
TI  - Minimal model of directed cell motility on patterned substrates.
AB  - Crawling cell motility is vital to many biological processes such as wound
      healing and the immune response. Using a minimal model we investigate the effects
      of patterned substrate adhesiveness and biophysical cell parameters on the
      direction of cell motion. We show that cells with low adhesion site formation
      rates may move perpendicular to adhesive stripes while those with high adhesion
      site formation rates results in motility only parallel to the substrate stripes.
      We explore the effects of varying the substrate pattern geometry and the strength
      of actin polymerization on the directionality of the crawling cell. These results
      reveal that high strength of actin polymerization results in motion perpendicular
      to substrate stripes only when the substrate is relatively nonadhesive; in
      particular, this suggests potential applications in motile cell sorting and
      guiding on engineered substrates.

PMID- 29347668
TI  - Enabling the self-contained refrigerator to work beyond its limits by filtering
      the reservoirs.
AB  - In this paper, we study the quantum self-contained refrigerator [Linden et al.,
      Phys. Rev. Lett. 105, 130401 (2010)PRLTAO0031-900710.1103/PhysRevLett.105.130401]
      in the strong internal coupling regime with engineered reservoirs. We find that
      if some modes of the three thermal reservoirs can be properly filtered out, the
      efficiency and the working domain of the refrigerator can be improved in contrast
      to the those in the weak internal coupling regime, which indicates one advantage
      of the strong internal coupling. In addition, we find that the background natural
      vacuum reservoir could cause the filtered refrigerator to stop working and the
      background natural thermal reservoir could greatly reduce the cooling efficiency.

PMID- 29347669
TI  - Reply to "Comment on 'Troublesome aspects of the Renyi-MaxEnt treatment' ".
AB  - This Reply is intended as a refutation of the preceding Comment [Oikonomou and
      Bagci, Phys. Rev. E 96, 056101 (2017)10.1103/PhysRevE.96.056101] on our paper
      [Plastino et al., Phys. Rev. E 94, 012145 (2016).1539
      375510.1103/PhysRevE.94.012145]. We show that the Tsallis probability
      distribution of our paper does not coincide with the Tsallis distribution studied
      by Oikonomou and Bagci. Consequently, their findings do not apply to our paper.

PMID- 29347670
TI  - Comment on "Troublesome aspects of the Renyi-MaxEnt treatment".
AB  - Plastino et al. [Plastino et al., Phys. Rev. E 94, 012145 (2016)1539
      375510.1103/PhysRevE.94.012145] recently stated that the Renyi entropy is not
      suitable for thermodynamics by using functional calculus, since it leads to
      anomalous results unlike the Tsallis entropy. We first show that the Tsallis
      entropy also leads to such anomalous behaviors if one adopts the same functional
      calculus approach. Second, we note that one of the Lagrange multipliers is set in
      an ad hoc manner in the functional calculus approach of Plastino et al. Finally,
      the explanation for these anomalous behaviors is provided by observing that the
      generalized distributions obtained by Plastino et al. do not yield the ordinary
      canonical partition function in the appropriate limit and therefore cannot be
      considered as genuine generalized distributions.

PMID- 29347671
TI  - Kinetic-contact-driven gigantic energy transfer in a two-dimensional Lennard
      Jones fluid confined to a rotating pore.
AB  - A two-dimensional Lennard-Jones system in a circular and rotating container has
      been studied by means of molecular dynamics technique. A nonequilibrium
      transition to the rotating stage has been detected in a delayed time since an
      instant switching of the frame rotation. This transition is attributed to the
      increase of the density at the wall because of the centrifugal force. At the same
      time the phase transition occurs, the inner system changes its configuration of
      the solid-state type into the liquid type. Impact of angular frequency and
      molecular roughness on the transport properties of the nonrotating and rotating
      systems is analyzed.

PMID- 29347672
TI  - Unified mean-field framework for susceptible-infected-susceptible epidemics on
      networks, based on graph partitioning and the isoperimetric inequality.
AB  - We propose an approximation framework that unifies and generalizes a number of
      existing mean-field approximation methods for the susceptible-infected
      susceptible (SIS) epidemic model on complex networks. We derive the framework,
      which we call the unified mean-field framework (UMFF), as a set of approximations
      of the exact Markovian SIS equations. Our main novelty is that we describe the
      mean-field approximations from the perspective of the isoperimetric problem,
      which results in bounds on the UMFF approximation error. These new bounds provide
      insight in the accuracy of existing mean-field methods, such as the N-intertwined
      mean-field approximation and heterogeneous mean-field method, which are contained
      by UMFF. Additionally, the isoperimetric inequality relates the UMFF
      approximation accuracy to the regularity notions of Szemeredi's regularity lemma.

PMID- 29347673
TI  - Response and correlation functions of nonlinear systems in equilibrium states.
AB  - In this paper, we study systematically a serial of correlation functions in some
      one-dimensional nonlinear lattices. Due to the energy conservation law, they are
      implicitly interdependent. Various transport coefficients are thus also
      connected. In the studies of the autocorrelations of local energy density and of
      local heat current, a general relation between diverging heat conduction and
      super heat diffusion has been proposed recently. We clarify that such a relation
      is valid only in systems without temperature pressure. In those with temperature
      pressure, a constant but nontrivial term appears. This term explains a previously
      observed fact that heat diffusion in such systems is always ballistic but heat
      conduction can diverge very slowly. Such a result not only disproves the
      existence of any general relation between diverging heat conduction and super
      heat diffusion, but it also breaks the long-term presumption that ballistic heat
      conduction and diffusion always coexist.

PMID- 29347674
TI  - Alternative derivation of exact law for compressible and isothermal
      magnetohydrodynamics turbulence.
AB  - The exact law for fully developed homogeneous compressible magnetohydrodynamics
      (CMHD) turbulence is derived. For an isothermal plasma, without the assumption of
      isotropy, the exact law is expressed as a function of the plasma velocity field,
      the compressible Alfven velocity, and the scalar density, instead of the Elsasser
      variables used in previous works. The theoretical results show four different
      types of terms that are involved in the nonlinear cascade of the total energy in
      the inertial range. Each category is examined in detail, in particular, those
      that can be written either as source or flux terms. Finally, the role of the
      background magnetic field B_{0} is highlighted and a comparison with the
      incompressible MHD (IMHD) model is discussed. This point is particularly
      important when testing this exact law on numerical simulations and in situ
      observations in space plasmas.

PMID- 29347675
TI  - Persistent Sinai-type diffusion in Gaussian random potentials with decaying
      spatial correlations.
AB  - Logarithmic or Sinai-type subdiffusion is usually associated with random force
      disorder and nonstationary potential fluctuations whose root-mean-squared
      amplitude grows with distance. We show here that extremely persistent,
      macroscopic logarithmic diffusion also universally emerges at sufficiently low
      temperatures in stationary Gaussian random potentials with spatially decaying
      correlations, known to exist in a broad range of physical systems. Combining
      results from extensive simulations with a scaling approach we elucidate the
      physical mechanism of this unusual subdiffusion. In particular, we explain why
      with growing temperature and/or time a first crossover occurs to standard, power
      law subdiffusion, with a time-dependent power-law exponent, and then a second
      crossover occurs to normal diffusion with a disorder-renormalized diffusion
      coefficient. Interestingly, the initial, nominally ultraslow diffusion turns out
      to be much faster than the universal de Gennes-Bassler-Zwanzig limit of the
      renormalized normal diffusion, which realistically cannot be attained at
      sufficiently low temperatures and/or for strong disorder. The ultraslow diffusion
      is also shown to be nonergodic and it displays a local bias phenomenon. Our
      simple scaling theory not only explains our numerical findings but qualitatively
      also has a predictive character.

PMID- 29347676
TI  - Twitching motility of bacteria with type-IV pili: Fractal walks, first passage
      time, and their consequences on microcolonies.
AB  - A human pathogen, Neisseria gonorrhoeae (NG), moves on surfaces by attaching and
      retracting polymeric structures called Type IV pili. The tug-of-war between the
      pili results in a two-dimensional stochastic motion called twitching motility. In
      this paper, with the help of real-time NG trajectories, we develop coarse-grained
      models for their description. The fractal properties of these trajectories are
      determined and their influence on first passage time and formation of bacterial
      microcolonies is studied. Our main observations are as follows: (i) NG performs a
      fast ballistic walk on small time scales and a slow diffusive walk over long time
      scales with a long crossover region; (ii) there exists a characteristic
      persistent length l_{p}^{*}, which yields the fastest growth of bacterial
      aggregates or biofilms. Our simulations reveal that l_{p}^{*}~L^{0.6}, where L*L
      is the surface on which the bacteria move; (iii) the morphologies have distinct
      fractal characteristics as a consequence of the ballistic and diffusive motion of
      the constituting bacteria.

PMID- 29347677
TI  - Sidewall-friction-driven ordering transition in granular channel flows:
      Implications for granular rheology.
AB  - We report a transition from a disordered state to an ordered state in the flow of
      nearly monodisperse granular matter flowing in an inclined channel with planar
      slide walls and a bumpy base, using discrete element method simulations. For low
      particle-sidewall friction coefficients, the flowing particles are disordered,
      however, for high sidewall friction, an ordered state is obtained, characterized
      by a layering of the particles and hexagonal packing of the particles in each
      layer. The extent of ordering, quantified by the local bond-orientational order
      parameter, varies in the cross section of the channel, with the highest ordering
      near the sidewalls. The flow transition significantly affects the local rheology
      the effective friction coefficient is lower, and the packing fraction is higher,
      in the ordered state compared to the disordered state. A simple model,
      incorporating the extent of local ordering, is shown to describe the rheology of
      the system.

PMID- 29347678
TI  - Detection of transition times from single-particle-tracking trajectories.
AB  - In heterogeneous environments, the diffusivity is not constant but changes with
      time. It is important to detect changes in the diffusivity from single-particle
      tracking trajectories in experiments. Here, we devise a novel method for
      detecting the transition times of the diffusivity from trajectory data. A key
      idea of this method is the introduction of a characteristic time scale of the
      diffusive states, which is obtained by a fluctuation analysis of the time
      averaged mean square displacements. We test our method in silico by using the
      Langevin equation with a fluctuating diffusivity. We show that our method can
      successfully detect the transition times of diffusive states and obtain the
      diffusion coefficient as a function of time. This method will provide a
      quantitative description of the fluctuating diffusivity in heterogeneous
      environments and can be applied to time series with transitions of states.

PMID- 29347679
TI  - Pathways to equilibrium orientation fluctuations in finite stripe-forming
      systems.
AB  - Small-angle orientation fluctuations in ordered stripe-forming systems free of
      topological defects can exhibit aging and anisotropic growth of two length
      scales. In infinitely extended systems, the stripe orientation field develops a
      dominant modulation length lambda_{?}^{*}(t) in the direction parallel to the
      stripes, which increases with time t as lambda_{?}^{*}(t)~t^{1/4}.
      Simultaneously, the orientation correlation length xi_{?}(t) in the direction
      perpendicular to the stripes increases as xi_{?}(t)~t^{1/2} [Riesch et al.,
      Interface Focus 7, 20160146 (2017)2042-889810.1098/rsfs.2016.0146]. Here we show
      that finite systems of size L_{?}*L_{?} with periodic boundary conditions reach
      equilibrium when the dominant modulation length lambda_{?}^{*}(t) reaches the
      system size L_{?} in the stripe direction. The equilibration time tau_{eq}^{?} is
      solely determined by L_{?}, with tau_{eq}^{?}~L_{?}^{4}. In systems with
      L_{?}<L_{?}^{2}/2pilambda_{p}, where lambda_{p} is the undulation penetration
      length, the initial aging and coarsening dynamics changes at the crossover time
      tau_{C}^{?}~L_{?}^{2} to an aging and coarsening dynamics described by the one
      dimensional Mullins-Herring equation, before reaching equilibrium at
      tau_{?}^{eq}. Our work reveals the two pathways to equilibrium in stripe phases
      with periodic boundary conditions, the finite-size scaling behavior of
      equilibrium orientation fluctuations, and the characteristic exponents associated
      with the influence of a finite system size.

PMID- 29347680
TI  - Directionality indices: Testing information transfer with surrogate correction.
AB  - Directionality indices can be used as an indicator of the asymmetry in coupling
      between systems and have found particular application in relation to neurological
      systems. The directionality index between two systems is a function of measures
      of information transfer in both directions. Here we illustrate that before
      inferring the directionality of coupling it is first necessary to consider the
      use of appropriate tests of significance. We propose a surrogate corrected
      directionality index which incorporates such testing. We also highlight the
      differences between testing the significance of the directionality index itself
      versus testing the individual measures of information transfer in each direction.
      To validate the approach we compared two different methods of estimating
      coupling, both of which have previously been used to estimate directionality
      indices. These were the modeling-based evolution map approach and a conditional
      mutual information (CMI) method for calculating dynamic information rates. For
      the CMI-based approach we also compared two different methods for estimating the
      CMI, an equiquantization-based estimator and a k-nearest neighbors estimator.

PMID- 29347681
TI  - Computation of the asymptotic states of modulated open quantum systems with a
      numerically exact realization of the quantum trajectory method.
AB  - Quantum systems out of equilibrium are presently a subject of active research,
      both in theoretical and experimental domains. In this work, we consider time
      periodically modulated quantum systems that are in contact with a stationary
      environment. Within the framework of a quantum master equation, the asymptotic
      states of such systems are described by time-periodic density operators.
      Resolution of these operators constitutes a nontrivial computational task.
      Approaches based on spectral and iterative methods are restricted to systems with
      the dimension of the hosting Hilbert space dimH=N?300, while the direct long-time
      numerical integration of the master equation becomes increasingly problematic for
      N?400, especially when the coupling to the environment is weak. To go beyond this
      limit, we use the quantum trajectory method, which unravels the master equation
      for the density operator into a set of stochastic processes for wave functions.
      The asymptotic density matrix is calculated by performing a statistical sampling
      over the ensemble of quantum trajectories, preceded by a long transient
      propagation. We follow the ideology of event-driven programming and construct a
      new algorithmic realization of the method. The algorithm is computationally
      efficient, allowing for long "leaps" forward in time. It is also numerically
      exact, in the sense that, being given the list of uniformly distributed (on the
      unit interval) random numbers, {eta_{1},eta_{2},...,eta_{n}}, one could propagate
      a quantum trajectory (with eta_{i}'s as norm thresholds) in a numerically exact
      way. By using a scalable N-particle quantum model, we demonstrate that the
      algorithm allows us to resolve the asymptotic density operator of the model
      system with N=2000 states on a regular-size computer cluster, thus reaching the
      scale on which numerical studies of modulated Hamiltonian systems are currently
      performed.

PMID- 29347682
TI  - Front propagation in a regular vortex lattice: Dependence on the vortex
      structure.
AB  - We investigate the dependence on the vortex structure of the propagation of
      fronts in stirred flows. For this, we consider a regular set of vortices whose
      structure is changed by varying both their boundary conditions and their aspect
      ratios. These configurations are investigated experimentally in autocatalytic
      solutions stirred by electroconvective flows and numerically from kinematic
      simulations based on the determination of the dominant Fourier mode of the vortex
      stream function in each of them. For free lateral boundary conditions, i.e., in
      an extended vortex lattice, it is found that both the flow structure and the
      front propagation negligibly depend on vortex aspect ratios. For rigid lateral
      boundary conditions, i.e., in a vortex chain, vortices involve a slight
      dependence on their aspect ratios which surprisingly yields a noticeable decrease
      of the enhancement of front velocity by flow advection. These different behaviors
      reveal a sensitivity of the mean front velocity on the flow subscales. It
      emphasizes the intrinsic multiscale nature of front propagation in stirred flows
      and the need to take into account not only the intensity of vortex flows but also
      their inner structure to determine front propagation at a large scale.
      Differences between experiments and simulations suggest the occurrence of
      secondary flows in vortex chains at large velocity and large aspect ratios.

PMID- 29347683
TI  - Crossover between the Gaussian orthogonal ensemble, the Gaussian unitary
      ensemble, and Poissonian statistics.
AB  - Until now only for specific crossovers between Poissonian statistics (P), the
      statistics of a Gaussian orthogonal ensemble (GOE), or the statistics of a
      Gaussian unitary ensemble (GUE) have analytical formulas for the level spacing
      distribution function been derived within random matrix theory. We investigate
      arbitrary crossovers in the triangle between all three statistics. To this aim we
      propose an according formula for the level spacing distribution function
      depending on two parameters. Comparing the behavior of our formula for the
      special cases of P->GUE, P->GOE, and GOE->GUE with the results from random matrix
      theory, we prove that these crossovers are described reasonably. Recent
      investigations by F. Schweiner et al. [Phys. Rev. E 95, 062205 (2017)2470
      004510.1103/PhysRevE.95.062205] have shown that the Hamiltonian of
      magnetoexcitons in cubic semiconductors can exhibit all three statistics in
      dependence on the system parameters. Evaluating the numerical results for
      magnetoexcitons in dependence on the excitation energy and on a parameter
      connected with the cubic valence band structure and comparing the results with
      the formula proposed allows us to distinguish between regular and chaotic
      behavior as well as between existent or broken antiunitary symmetries. Increasing
      one of the two parameters, transitions between different crossovers, e.g., from
      the P->GOE to the P->GUE crossover, are observed and discussed.

PMID- 29347684
TI  - Scalable and fast heterogeneous molecular simulation with predictive
      parallelization schemes.
AB  - Multiscale and inhomogeneous molecular systems are challenging topics in the
      field of molecular simulation. In particular, modeling biological systems in the
      context of multiscale simulations and exploring material properties are driving a
      permanent development of new simulation methods and optimization algorithms. In
      computational terms, those methods require parallelization schemes that make a
      productive use of computational resources for each simulation and from its
      genesis. Here, we introduce the heterogeneous domain decomposition approach,
      which is a combination of an heterogeneity-sensitive spatial domain decomposition
      with an a priori rearrangement of subdomain walls. Within this approach, the
      theoretical modeling and scaling laws for the force computation time are proposed
      and studied as a function of the number of particles and the spatial resolution
      ratio. We also show the new approach capabilities, by comparing it to both static
      domain decomposition algorithms and dynamic load-balancing schemes. Specifically,
      two representative molecular systems have been simulated and compared to the
      heterogeneous domain decomposition proposed in this work. These two systems
      comprise an adaptive resolution simulation of a biomolecule solvated in water and
      a phase-separated binary Lennard-Jones fluid.

PMID- 29347685
TI  - Statistical independence of the initial conditions in chaotic mixing.
AB  - Experimental evidence of the scalar convergence towards a global strange
      eigenmode independent of the scalar initial condition in chaotic mixing is
      provided. This convergence, underpinning the independent nature of chaotic mixing
      in any passive scalar, is presented by scalar fields with different initial
      conditions casting statistically similar shapes when advected by periodic
      unsteady flows. As the scalar patterns converge towards a global strange
      eigenmode, the scalar filaments, locally aligned with the direction of maximum
      stretching, as described by the Lagrangian stretching theory, stack together in
      an inhomogeneous pattern at distances smaller than their asymptotic minimum
      widths. The scalar variance decay becomes then exponential and independent of the
      scalar diffusivity or initial condition. In this work, mixing is achieved by
      advecting the scalar using a set of laminar flows with unsteady periodic
      topology. These flows, that resemble the tendril-whorl map, are obtained by
      morphing the forcing geometry in an electromagnetic free surface 2D mixing
      experiment. This forcing generates a velocity field which periodically switches
      between two concentric hyperbolic and elliptic stagnation points. In agreement
      with previous literature, the velocity fields obtained produce a chaotic mixer
      with two regions: a central mixing and an external extensional area. These two
      regions are interconnected through two pairs of fluid conduits which transfer
      clean and dyed fluid from the extensional area towards the mixing region and a
      homogenized mixture from the mixing area towards the extensional region.

PMID- 29347686
TI  - Geometric phaselike effects in a quantum heat engine.
AB  - By periodically driving the temperature of reservoirs in a quantum heat engine,
      geometric or Pancharatnam-Berry phaselike (PBp) effects in the thermodynamics can
      be observed. The PBp can be identified from a generating function (GF) method
      within an adiabatic quantum Markovian master equation formalism. The GF is shown
      not to lead to a standard open quantum system's fluctuation theorem in the
      presence of phase-different modulations with an inapplicability in the use of
      large deviation theory. Effect of quantum coherences in optimizing the flux is
      nullified due to PBp contributions. The linear coefficient, 1/2, which is
      universal in the expansion of the efficiency at maximum power in terms of Carnot
      efficiency no longer holds true in the presence of PBp effects.

PMID- 29347687
TI  - Corrected simulations for one-dimensional diffusion processes with naturally
      occurring boundaries.
AB  - To simulate a diffusion process, a usual approach is to discretize the time in
      the associated stochastic differential equation. This is the approach used in the
      Euler method. In the present work we consider a one-dimensional diffusion process
      where the terms occurring, within the stochastic differential equation, prevent
      the process entering a region. The outcome is a naturally occurring boundary
      (which may be absorbing or reflecting). A complication occurs in a simulation of
      this situation. The term involving a random variable, within the discretized
      stochastic differential equation, may take a trajectory across the boundary into
      a "forbidden region." The naive way of dealing with this problem, which we refer
      to as the "standard" approach, is simply to reset the trajectory to the boundary,
      based on the argument that crossing the boundary actually signifies achieving the
      boundary. In this work we show, within the framework of the Euler method, that
      such resetting introduces a spurious force into the original diffusion process.
      This force may have a significant influence on trajectories that come close to a
      boundary. We propose a corrected numerical scheme, for simulating one-dimensional
      diffusion processes with naturally occurring boundaries. This involves correcting
      the standard approach, so that an exact property of the diffusion process is
      precisely respected. As a consequence, the proposed scheme does not introduce a
      spurious force into the dynamics. We present numerical test cases, based on
      exactly soluble one-dimensional problems with one or two boundaries, which
      suggest that, for a given value of the discrete time step, the proposed scheme
      leads to substantially more accurate results than the standard approach.
      Alternatively, the standard approach needs considerably more computation time to
      obtain a comparable level of accuracy to the proposed scheme, because the
      standard approach requires a significantly smaller time step.

PMID- 29347688
TI  - Infection dynamics on spatial small-world network models.
AB  - The study of complex networks, and in particular of social networks, has mostly
      concentrated on relational networks, abstracting the distance between nodes.
      Spatial networks are, however, extremely relevant in our daily lives, and a large
      body of research exists to show that the distances between nodes greatly
      influence the cost and probability of establishing and maintaining a link. A
      random geometric graph (RGG) is the main type of synthetic network model used to
      mimic the statistical properties and behavior of many social networks. We propose
      a model, called REDS, that extends energy-constrained RGGs to account for the
      synergic effect of sharing the cost of a link with our neighbors, as is observed
      in real relational networks. We apply both the standard Watts-Strogatz rewiring
      procedure and another method that conserves the degree distribution of the
      network. The second technique was developed to eliminate unwanted forms of
      spatial correlation between the degree of nodes that are affected by rewiring,
      limiting the effect on other properties such as clustering and assortativity. We
      analyze both the statistical properties of these two network types and their
      epidemiological behavior when used as a substrate for a standard susceptible
      infected-susceptible compartmental model. We consider and discuss the differences
      in properties and behavior between RGGs and REDS as rewiring increases and as
      infection parameters are changed. We report considerable differences both between
      the network types and, in the case of REDS, between the two rewiring schemes. We
      conclude that REDS represent, with the application of these rewiring mechanisms,
      extremely useful and interesting tools in the study of social and epidemiological
      phenomena in synthetic complex networks.

PMID- 29347689
TI  - Improved locality of the phase-field lattice-Boltzmann model for immiscible
      fluids at high density ratios.
AB  - Based on phase-field theory, we introduce a robust lattice-Boltzmann equation for
      modeling immiscible multiphase flows at large density and viscosity contrasts.
      Our approach is built by modifying the method proposed by Zu and He [Phys. Rev. E
      87, 043301 (2013)PLEEE81539-375510.1103/PhysRevE.87.043301] in such a way as to
      improve efficiency and numerical stability. In particular, we employ a different
      interface-tracking equation based on the so-called conservative phase-field
      model, a simplified equilibrium distribution that decouples pressure and velocity
      calculations, and a local scheme based on the hydrodynamic distribution functions
      for calculation of the stress tensor. In addition to two distribution functions
      for interface tracking and recovery of hydrodynamic properties, the only nonlocal
      variable in the proposed model is the phase field. Moreover, within our framework
      there is no need to use biased or mixed difference stencils for numerical
      stability and accuracy at high density ratios. This not only simplifies the
      implementation and efficiency of the model, but also leads to a model that is
      better suited to parallel implementation on distributed-memory machines. Several
      benchmark cases are considered to assess the efficacy of the proposed model,
      including the layered Poiseuille flow in a rectangular channel, Rayleigh-Taylor
      instability, and the rise of a Taylor bubble in a duct. The numerical results are
      in good agreement with available numerical and experimental data.

PMID- 29347690
TI  - Inherent stress correlations in a quiescent two-dimensional liquid: Static
      analysis including finite-size effects.
AB  - After constructing a formalism to analyze spatial stress correlations in two
      dimensional equilibrated liquids, we show that the sole conjunction of mechanical
      balance and material isotropy demands all anisotropic components of the inherent
      state (IS) stress autocorrelation matrix to decay at long range as 1/r^{2} in the
      large system size limit. Furthermore, analyzing numerical simulation data for an
      equilibrated supercooled liquid, we bring evidence that, in finite-sized periodic
      systems, the autocorrelations of pressure and shear stresses present uniform
      backgrounds of amplitudes proportional to the inverse cell area. These
      backgrounds bring relevant contributions to macroscopic IS stress fluctuations,
      with the consequence that the latter scale as inverse area, yet in an anomalous
      way, inconsistent with viewing an IS as equivalent, in the thermodynamic limit,
      to an ensemble of independent finite-sized subsystems. In that sense, ISs are not
      spatially ergodic.

PMID- 29347691
TI  - Dynamics of functional failures and recovery in complex road networks.
AB  - We propose a new framework for modeling the evolution of functional failures and
      recoveries in complex networks, with traffic congestion on road networks as the
      case study. Differently from conventional approaches, we transform the evolution
      of functional states into an equivalent dynamic structural process: dual-vertex
      splitting and coalescing embedded within the original network structure. The
      proposed model successfully explains traffic congestion and recovery patterns at
      the city scale based on high-resolution data from two megacities. Numerical
      analysis shows that certain network structural attributes can amplify or suppress
      cascading functional failures. Our approach represents a new general framework to
      model functional failures and recoveries in flow-based networks and allows
      understanding of the interplay between structure and function for flow-induced
      failure propagation and recovery.

PMID- 29347692
TI  - Effect of the correlation between internal noise and external noise on logical
      stochastic resonance in bistable systems.
AB  - Some noisy nonlinear systems could be exploited to operate reliable logic
      operation in an optimal window of noise intensity, which is termed as logical
      stochastic resonance (LSR). We investigated the LSR phenomenon in bistable
      systems when internal noise and external noise are correlated. The LSR effect is
      evaluated by the success probability of the obtained desired output with various
      combinations of logic inputs. It is shown that the or-nor, and-nand, and Latch
      operations still can operate reliably with the correlated internal noise and
      external noise. A positive correlation strength tends to enhance or-nor logic and
      suppress and-nand logic. The negative correlation strength tends to suppress or
      nor logic and enhance and-nand logic. The results provide possible corroboration
      for implementing reliable LSR when internal noise and external noise are
      correlated.

PMID- 29347693
TI  - Flow instabilities due to the interfacial formation of surfactant-fatty acid
      material in a Hele-Shaw cell.
AB  - We present an experimental study of pattern formation during the penetration of
      an aqueous surfactant solution into a liquid fatty acid in a Hele-Shaw cell. When
      a solution of the cationic surfactant cetylpyridinium chloride is injected into
      oleic acid, a wide variety of fingering patterns are observed as a function of
      surfactant concentration and flow rate, which are strikingly different than the
      classic Saffman-Taylor (ST) instability. We observe evidence of interfacial
      material forming between the two liquids, causing these instabilities. Moreover,
      the number of fingers decreases with increasing flow rate Q, while the average
      finger width increases with Q, both trends opposite to the ST case. Bulk rheology
      on related mixtures indicates a gel-like state. Comparison of experiments using
      other oils indicates the importance of pH and the carboxylic head group in the
      formation of the surfactant-fatty acid material.

PMID- 29347694
TI  - Constraint percolation on hyperbolic lattices.
AB  - Hyperbolic lattices interpolate between finite-dimensional lattices and Bethe
      lattices, and they are interesting in their own right, with ordinary percolation
      exhibiting not one but two phase transitions. We study four constraint
      percolation models-k-core percolation (for k=1,2,3) and force-balance percolation
      on several tessellations of the hyperbolic plane. By comparing these four
      different models, our numerical data suggest that all of the k-core models, even
      for k=3, exhibit behavior similar to ordinary percolation, while the force
      balance percolation transition is discontinuous. We also provide proof, for some
      hyperbolic lattices, of the existence of a critical probability that is less than
      unity for the force-balance model, so that we can place our interpretation of the
      numerical data for this model on a more rigorous footing. Finally, we discuss
      improved numerical methods for determining the two critical probabilities on the
      hyperbolic lattice for the k-core percolation models.

PMID- 29347695
TI  - Optimal dephasing for ballistic energy transfer in disordered linear chains.
AB  - We study the interplay between dephasing, disorder, and coupling to a sink on
      transport efficiency in a one-dimensional chain of finite length N, and in
      particular the beneficial or detrimental effect of dephasing on transport. The
      excitation moves along the chain by coherent nearest-neighbor hopping Omega,
      under the action of static disorder W and dephasing gamma. The last site is
      coupled to an external acceptor system (sink), where the excitation can be
      trapped with a rate Gamma_{trap}. While it is known that dephasing can help
      transport in the localized regime, here we show that dephasing can enhance energy
      transfer even in the ballistic regime. Specifically, in the localized regime we
      recover previous results, where the optimal dephasing is independent of the chain
      length and proportional to W or W^{2}/Omega. In the ballistic regime, the optimal
      dephasing decreases as 1/N or 1/sqrt[N], respectively, for weak and moderate
      static disorder. When focusing on the excitation starting at the beginning of the
      chain, dephasing can help excitation transfer only above a critical value of
      disorder W^{cr}, which strongly depends on the sink coupling strength
      Gamma_{trap}. Analytic solutions are obtained for short chains.

PMID- 29347697
TI  - Multichannel scattering problem with a nonseparable angular part as a boundary
      value problem.
AB  - We have developed an efficient computational method for solving the quantum
      multichannel scattering problem with a nonseparable angular part. The use of the
      nondirect product discrete-variable representation, suggested and developed by V.
      Melezhik, gives us an accurate approximation for the angular part of the desired
      wave function and, eventually, for the scattering parameters. Subsequent
      reduction of the problem to the boundary-value problem with well-defined block
      band matrix of equation coefficients permits us to use efficient standard
      algorithms for its solution. We demonstrate the numerical efficiency,
      flexibility, and good convergence of the computational scheme in a quantitative
      description of the Feshbach resonances in pair collisions occurring in atomic
      traps and the scattering in strongly anisotropic traps. The method can also be
      used for the investigation of further actual problems in quantum physics. A
      natural extension is a description of spin-orbit coupling, intensively
      investigated in ultracold gases, and dipolar confinement-induced resonances.

PMID- 29347696
TI  - Stochastic dynamics of genetic broadcasting networks.
AB  - The complex genetic programs of eukaryotic cells are often regulated by key
      transcription factors occupying or clearing out of a large number of genomic
      locations. Orchestrating the residence times of these factors is therefore
      important for the well organized functioning of a large network. The classic
      models of genetic switches sidestep this timing issue by assuming the binding of
      transcription factors to be governed entirely by thermodynamic protein-DNA
      affinities. Here we show that relying on passive thermodynamics and random
      release times can lead to a "time-scale crisis" for master genes that broadcast
      their signals to a large number of binding sites. We demonstrate that this time
      scale crisis for clearance in a large broadcasting network can be resolved by
      actively regulating residence times through molecular stripping. We illustrate
      these ideas by studying a model of the stochastic dynamics of the genetic network
      of the central eukaryotic master regulator NFkappaB which broadcasts its signals
      to many downstream genes that regulate immune response, apoptosis, etc.

PMID- 29347698
TI  - Field dynamics inference via spectral density estimation.
AB  - Stochastic differential equations are of utmost importance in various scientific
      and industrial areas. They are the natural description of dynamical processes
      whose precise equations of motion are either not known or too expensive to solve,
      e.g., when modeling Brownian motion. In some cases, the equations governing the
      dynamics of a physical system on macroscopic scales occur to be unknown since
      they typically cannot be deduced from general principles. In this work, we
      describe how the underlying laws of a stochastic process can be approximated by
      the spectral density of the corresponding process. Furthermore, we show how the
      density can be inferred from possibly very noisy and incomplete measurements of
      the dynamical field. Generally, inverse problems like these can be tackled with
      the help of Information Field Theory. For now, we restrict to linear and
      autonomous processes. To demonstrate its applicability, we employ our
      reconstruction algorithm on a time-series and spatiotemporal processes.

PMID- 29347699
TI  - Dynamic scaling in the two-dimensional Ising spin glass with normal-distributed
      couplings.
AB  - We carry out simulated annealing and employ a generalized Kibble-Zurek scaling
      hypothesis to study the two-dimensional Ising spin glass with normal-distributed
      couplings. The system has an equilibrium glass transition at temperature T=0.
      From a scaling analysis when T->0 at different annealing velocities v, we find
      power-law scaling in the system size for the velocity required in order to relax
      toward the ground state, v~L^{-(z+1/nu)}, the Kibble-Zurek ansatz where z is the
      dynamic critical exponent and nu the previously known correlation-length
      exponent, nu~3.6. We find z~13.6 for both the Edwards-Anderson spin-glass order
      parameter and the excess energy. This is different from a previous study of the
      system with bimodal couplings [Rubin et al., Phys. Rev. E 95, 052133 (2017)2470
      004510.1103/PhysRevE.95.052133] where the dynamics is faster (z is smaller) and
      the above two quantities relax with different dynamic exponents (with that of the
      energy being larger). We argue that the different behaviors arise as a
      consequence of the different low-energy landscapes: for normal-distributed
      couplings the ground state is unique (up to a spin reflection), while the system
      with bimodal couplings is massively degenerate. Our results reinforce the
      conclusion of anomalous entropy-driven relaxation behavior in the bimodal Ising
      glass. In the case of a continuous coupling distribution, our results presented
      here also indicate that, although Kibble-Zurek scaling holds, the perturbative
      behavior normally applying in the slow limit breaks down, likely due to
      quasidegenerate states, and the scaling function takes a different form.

PMID- 29347700
TI  - Numerical design of a T-shaped microfluidic device for deformability-based
      separation of elastic capsules and soft beads.
AB  - We propose a square cross-section microfluidic channel with an orthogonal side
      branch (asymmetric T-shaped bifurcation) for the separation of elastic capsules
      and soft beads suspended in a Newtonian liquid on the basis of their mechanical
      properties. The design is performed through three-dimensional direct numerical
      simulations. When suspended objects start near the inflow channel centerline and
      the carrier fluid is equally partitioned between the two outflow branches,
      particle separation can be achieved based on their deformability, with the
      stiffer ones going "straight" and the softer ones being deviated to the "side"
      branch. The effects of the geometrical and physical parameters of the system on
      the phenomenon are investigated. Since cell deformability can be significantly
      modified by pathology, we give a proof of concept on the possibility of
      separating diseased cells from healthy ones, thus leading to illness diagnosis.

PMID- 29347701
TI  - Speed-of-light pulses in the massless nonlinear Dirac equation with a potential.
AB  - We consider the massless nonlinear Dirac (NLD) equation in 1+1 dimension with
      scalar-scalar self-interaction g^{2}/2(Psi[over -]Psi)^{2} in the presence of
      three external electromagnetic real potentials V(x), a potential barrier, a
      constant potential, and a potential well. By solving numerically the NLD
      equation, we find different scenarios depending on initial conditions, namely,
      propagation of the initial pulse along one direction, splitting of the initial
      pulse into two pulses traveling in opposite directions, and focusing of two
      initial pulses followed by a splitting. For all considered cases, the final waves
      travel with the speed of light and are solutions of the massless linear Dirac
      equation. During these processes the charge and the energy are conserved, whereas
      the momentum is conserved when the solutions possess specific symmetries. For the
      case of the constant potential, we derive exact analytical solutions of the
      massless NLD equation that are also solutions of the massless linearized Dirac
      equation. Decay or growth of the initial pulse is also predicted from the
      evolution of the charge for the case of a non-zero imaginary part of the
      potential.

PMID- 29347702
TI  - Orbitals for classical arbitrary anisotropic colloidal potentials.
AB  - Coarse-grained potentials are ubiquitous in mesoscale simulations. While various
      methods to compute effective interactions for spherically symmetric particles
      exist, anisotropic interactions are seldom used, due to their complexity. Here we
      describe a general formulation, based on a spatial decomposition of the density
      fields around the particles, akin to atomic orbitals. We show that anisotropic
      potentials can be efficiently computed in numerical simulations using Fourier
      based methods. We validate the field formulation and characterize its
      computational efficiency with a system of colloids that have Gaussian surface
      charge distributions. We also investigate the phase behavior of charged Janus
      colloids immersed in screened media, with screening lengths comparable to the
      colloid size. The system shows rich behaviors, exhibiting vapor, liquid, gel, and
      crystalline morphologies, depending on temperature and screening length. The
      crystalline phase only appears for symmetric Janus particles. For very short
      screening lengths, the system undergoes a direct transition from a vapor to a
      crystal on cooling; while, for longer screening lengths, a vapor-liquid-crystal
      transition is observed. The proposed formulation can be extended to model force
      fields that are time or orientation dependent, such as those in systems of
      polymer-grafted particles and magnetic colloids.

PMID- 29347703
TI  - Detecting the chaotic nature in a transitional boundary layer using symbolic
      information-theory quantifiers.
AB  - The permutation entropy and the statistical complexity are employed to study the
      boundary-layer transition induced by the surface roughness. The velocity signals
      measured in the transition process are analyzed with these symbolic quantifiers,
      as well as the complexity-entropy causality plane, and the chaotic nature of the
      instability fluctuations is identified. The frequency of the dominant
      fluctuations has been found according to the time scales corresponding to the
      extreme values of the symbolic quantifiers. The laminar-turbulent transition
      process is accompanied by the evolution in the degree of organization of the
      complex eddy motions, which is also characterized with the growing smaller and
      flatter circles in the complexity-entropy causality plane. With the help of the
      permutation entropy and the statistical complexity, the differences between the
      chaotic fluctuations detected in the experiments and the classical Tollmien
      Schlichting wave are shown and discussed. It is also found that the chaotic
      features of the instability fluctuations can be approximated with a number of
      regular sine waves superimposed on the fluctuations of the undisturbed laminar
      boundary layer. This result is related to the physical mechanism in the
      generation of the instability fluctuations, which is the noise-induced chaos.

PMID- 29347704
TI  - Recurrence due to periodic multisoliton fission in the defocusing nonlinear
      Schrodinger equation.
AB  - We address the degree of universality of the Fermi-Pasta-Ulam recurrence induced
      by multisoliton fission from a harmonic excitation by analyzing the case of the
      semiclassical defocusing nonlinear Schrodinger equation, which models nonlinear
      wave propagation in a variety of physical settings. Using a suitable Wentzel
      Kramers-Brillouin approach to the solution of the associated scattering problem
      we accurately predict, in a fully analytical way, the number and the features
      (amplitude and velocity) of solitonlike excitations emerging post-breaking, as a
      function of the dispersion smallness parameter. This also permits us to predict
      and analyze the near-recurrences, thereby inferring the universal character of
      the mechanism originally discovered for the Korteweg-deVries equation. We show,
      however, that important differences exist between the two models, arising from
      the different scaling rules obeyed by the soliton velocities.

PMID- 29347705
TI  - Exploring cluster Monte Carlo updates with Boltzmann machines.
AB  - Boltzmann machines are physics informed generative models with broad applications
      in machine learning. They model the probability distribution of an input data set
      with latent variables and generate new samples accordingly. Applying the
      Boltzmann machines back to physics, they are ideal recommender systems to
      accelerate the Monte Carlo simulation of physical systems due to their
      flexibility and effectiveness. More intriguingly, we show that the generative
      sampling of the Boltzmann machines can even give different cluster Monte Carlo
      algorithms. The latent representation of the Boltzmann machines can be designed
      to mediate complex interactions and identify clusters of the physical system. We
      demonstrate these findings with concrete examples of the classical Ising model
      with and without four-spin plaquette interactions. In the future, automatic
      searches in the algorithm space parametrized by Boltzmann machines may discover
      more innovative Monte Carlo updates.

PMID- 29347706
TI  - Oscillation collapse in coupled quantum van der Pol oscillators.
AB  - The classical self-oscillations can collapse merely due to their mutual
      couplings. We investigate this oscillation collapse in quantum van der Pol
      oscillators. For a pair of quantum oscillators, the steady-state mean phonon
      number is shown to be lower than in the corresponding classical model with a
      Gaussian white noise that mimics quantum noise. We further show within the mean
      field theory that a number of globally coupled oscillators undergo a transition
      from the synchronized periodic motion to the collective oscillation collapse. A
      quantum many-body simulation suggests that the increase in the number of
      oscillators leads to a lower steady-state mean phonon number, bounded below by
      the mean-field result.

PMID- 29347707
TI  - Current quantization and fractal hierarchy in a driven repulsive lattice gas.
AB  - Driven lattice gases are widely regarded as the paradigm of collective phenomena
      out of equilibrium. While such models are usually studied with nearest-neighbor
      interactions, many empirical driven systems are dominated by slowly decaying
      interactions such as dipole-dipole and Van der Waals forces. Motivated by this
      gap, we study the nonequilibrium stationary state of a driven lattice gas with
      slow-decayed repulsive interactions at zero temperature. By numerical and
      analytical calculations of the particle current as a function of the density and
      of the driving field, we identify (i) an abrupt breakdown transition between
      insulating and conducting states, (ii) current quantization into discrete phases
      where a finite current flows with infinite differential resistivity, and (iii) a
      fractal hierarchy of excitations, related to the Farey sequences of number
      theory. We argue that the origin of these effects is the competition between
      scales, which also causes the counterintuitive phenomenon that crystalline states
      can melt by increasing the density.

PMID- 29347708
TI  - Inverse Bremsstrahlung current drive.
AB  - The generation of the plasma current resulting from Bremsstrahlung absorption is
      considered. It is shown that the electric current is higher than the naive
      estimates assuming that electrons absorb only the photon momentum and using the
      Spitzer conductivity would suggest. The current enhancement is in part because
      electrons get the recoil momentum from the Coulomb field of ions during the
      absorption and in part because the electromagnetic power is absorbed
      asymmetrically within the electron velocity distribution space.

PMID- 29347709
TI  - Interaction of a planar reacting shock wave with an isotropic turbulent vorticity
      field.
AB  - Linear interaction analysis (LIA) is employed to investigate the interaction of
      reactive and nonreactive shock waves with isotropic vortical turbulence. The
      analysis is carried out, through Laplace-transform technique, accounting for long
      time effects of vortical disturbances on the burnt-gas flow in the fast-reaction
      limit, where the reaction-region thickness is significantly small in comparison
      with the most representative turbulent length scales. Results provided by the
      opposite slow-reaction limit are also recollected. The reactive case is here
      restricted to situations where the overdriven detonation front does not exhibit
      self-induced oscillations nor inherent instabilities. The interaction of the
      planar detonation with a monochromatic pattern of perturbations is addressed
      first, and then a Fourier superposition for three-dimensional isotropic turbulent
      fields is employed to provide integral formulas for the amplification of the
      kinetic energy, enstrophy, and anisotropy downstream. Transitory evolution is
      also provided for single-frequency disturbances. In addition, further effects
      associated to the reaction rate, which have not been included in LIA, are studied
      through direct numerical simulations. The numerical computations, based on WENO
      BO4-type scheme, provide spatial profiles of the turbulent structures downstream
      for four different conditions that include nonreacting shock waves, unstable
      reacting shock (sufficiently high activation energy), and stable reacting shocks
      for different detonation thicknesses. Effects of the propagation Mach number,
      chemical heat release, and burn rate are analyzed.

PMID- 29347710
TI  - Entropic nonadditivity, H theorem, and nonlinear Klein-Kramers equations.
AB  - We use the H theorem to establish the entropy and the entropic additivity law for
      a system composed of subsystems, with the dynamics governed by the Klein-Kramers
      equations, by considering relations among the dynamics of these subsystems and
      their entropies. We start considering the subsystems governed by linear Klein
      Kramers equations and verify that the Boltzmann-Gibbs entropy is appropriated to
      this dynamics, leading us to the standard entropic additivity,
      S_{BG}^{(1?2)}=S_{BG}^{1}+S_{BG}^{2}, consistent with the fact that the
      distributions of the subsystem are independent. We then extend the dynamics of
      these subsystems to independent nonlinear Klein-Kramers equations. For this case,
      the results show that the H theorem is verified for a generalized entropy, which
      does not preserve the standard entropic additivity for independent distributions.
      In this scenario, consistent results are obtained when a suitable coupling among
      the nonlinear Klein-Kramers equations is considered, in which each subsystem
      modifies the other until an equilibrium state is reached. This dynamics, for the
      subsystems, results in the Tsallis entropy for the system and, consequently,
      verifies the relation S_{q}^{(1?2)}=S_{q}^{1}+S_{q}^{2}+(1
      q)S_{q}^{1}S_{q}^{2}/k, which is a nonadditive entropic relation.

PMID- 29347711
TI  - Shock-wave-like structures induced by an exothermic neutralization reaction in
      miscible fluids.
AB  - We report shock-wave-like structures that are strikingly different from
      previously observed fingering instabilities, which occur in a two-layer system of
      miscible fluids reacting by a second-order reaction A+B->S in a vertical Hele
      Shaw cell. While the traditional analysis expects the occurrence of a diffusion
      controlled convection, we show both experimentally and theoretically that the
      exothermic neutralization reaction can also trigger a wave with a perfectly
      planar front and nearly discontinuous change in density across the front. This
      wave propagates fast compared with the characteristic diffusion times and
      separates the motionless fluid and the area with anomalously intense convective
      mixing. We explain its mechanism and introduce a new dimensionless parameter,
      which allows to predict the appearance of such a pattern in other systems.
      Moreover, we show that our governing equations, taken in the inviscid limit, are
      formally analogous to well-known shallow-water equations and adiabatic gas flow
      equations. Based on this analogy, we define the critical velocity for the onset
      of the shock wave which is found to be in the perfect agreement with the
      experiments.

PMID- 29347712
TI  - From quenched disorder to continuous time random walk.
AB  - This work focuses on quantitative representation of transport in systems with
      quenched disorder. Explicit mapping of the quenched trap model to continuous time
      random walk is presented. Linear temporal transformation, t->t/Lambda^{1/alpha},
      for a transient process in the subdiffusive regime is sufficient for asymptotic
      mapping. An exact form of the constant Lambda^{1/alpha} is established. A
      disorder averaged position probability density function for a quenched trap model
      is obtained, and analytic expressions for the diffusion coefficient and drift are
      provided.

PMID- 29347713
TI  - Discrete Boltzmann modeling of Rayleigh-Taylor instability in two-component
      compressible flows.
AB  - A discrete Boltzmann model (DBM) is proposed to probe the Rayleigh-Taylor
      instability (RTI) in two-component compressible flows. Each species has a
      flexible specific-heat ratio and is described by one discrete Boltzmann equation
      (DBE). Independent discrete velocities are adopted for the two DBEs. The
      collision and force terms in the DBE account for the molecular collision and
      external force, respectively. Two types of force terms are exploited. In addition
      to recovering the modified Navier-Stokes equations in the hydrodynamic limit, the
      DBM has the capability of capturing detailed nonequilibrium effects. Furthermore,
      we use the DBM to investigate the dynamic process of the RTI. The invariants of
      tensors for nonequilibrium effects are presented and studied. For low Reynolds
      numbers, both global nonequilibrium manifestations and the growth rate of the
      entropy of mixing show three stages (i.e., the reducing, increasing, and then
      decreasing trends) in the evolution of the RTI. On the other hand, the early
      reducing tendency is suppressed and even eliminated for high Reynolds numbers.
      Relevant physical mechanisms are analyzed and discussed.

PMID- 29347714
TI  - Fluctuating hydrodynamics, current fluctuations, and hyperuniformity in boundary
      driven open quantum chains.
AB  - We consider a class of either fermionic or bosonic noninteracting open quantum
      chains driven by dissipative interactions at the boundaries and study the
      interplay of coherent transport and dissipative processes, such as bulk dephasing
      and diffusion. Starting from the microscopic formulation, we show that the
      dynamics on large scales can be described in terms of fluctuating hydrodynamics.
      This is an important simplification as it allows us to apply the methods of
      macroscopic fluctuation theory to compute the large deviation (LD) statistics of
      time-integrated currents. In particular, this permits us to show that fermionic
      open chains display a third-order dynamical phase transition in LD functions. We
      show that this transition is manifested in a singular change in the structure of
      trajectories: while typical trajectories are diffusive, rare trajectories
      associated with atypical currents are ballistic and hyperuniform in their spatial
      structure. We confirm these results by numerically simulating ensembles of rare
      trajectories via the cloning method, and by exact numerical diagonalization of
      the microscopic quantum generator.

PMID- 29347715
TI  - Cusps enable line attractors for neural computation.
AB  - Line attractors in neuronal networks have been suggested to be the basis of many
      brain functions, such as working memory, oculomotor control, head movement,
      locomotion, and sensory processing. In this paper, we make the connection between
      line attractors and pulse gating in feed-forward neuronal networks. In this
      context, because of their neutral stability along a one-dimensional manifold,
      line attractors are associated with a time-translational invariance that allows
      graded information to be propagated from one neuronal population to the next. To
      understand how pulse-gating manifests itself in a high-dimensional, nonlinear,
      feedforward integrate-and-fire network, we use a Fokker-Planck approach to
      analyze system dynamics. We make a connection between pulse-gated propagation in
      the Fokker-Planck and population-averaged mean-field (firing rate) models, and
      then identify an approximate line attractor in state space as the essential
      structure underlying graded information propagation. An analysis of the line
      attractor shows that it consists of three fixed points: a central saddle with an
      unstable manifold along the line and stable manifolds orthogonal to the line,
      which is surrounded on either side by stable fixed points. Along the manifold
      defined by the fixed points, slow dynamics give rise to a ghost. We show that
      this line attractor arises at a cusp catastrophe, where a fold bifurcation
      develops as a function of synaptic noise; and that the ghost dynamics near the
      fold of the cusp underly the robustness of the line attractor. Understanding the
      dynamical aspects of this cusp catastrophe allows us to show how line attractors
      can persist in biologically realistic neuronal networks and how the interplay of
      pulse gating, synaptic coupling, and neuronal stochasticity can be used to enable
      attracting one-dimensional manifolds and, thus, dynamically control the
      processing of graded information.

PMID- 29347716
TI  - Inferring low-dimensional microstructure representations using convolutional
      neural networks.
AB  - We apply recent advances in machine learning and computer vision to a central
      problem in materials informatics: the statistical representation of
      microstructural images. We use activations in a pretrained convolutional neural
      network to provide a high-dimensional characterization of a set of synthetic
      microstructural images. Next, we use manifold learning to obtain a low
      dimensional embedding of this statistical characterization. We show that the low
      dimensional embedding extracts the parameters used to generate the images.
      According to a variety of metrics, the convolutional neural network method yields
      dramatically better embeddings than the analogous method derived from two-point
      correlations alone.

PMID- 29347717
TI  - Crossover between liquidlike and gaslike behavior in CH_{4} at 400 K.
AB  - We report experimental evidence for a crossover between a liquidlike state and a
      gaslike state in fluid methane (CH_{4}). This crossover is observed in all of our
      experiments, up to a temperature of 397 K, 2.1 times the critical temperature of
      methane. The crossover has been characterized with both Raman spectroscopy and x
      ray diffraction in a number of separate experiments, and confirmed to be
      reversible. We associate this crossover with the Frenkel line-a recently
      hypothesized crossover in dynamic properties of fluids extending to arbitrarily
      high pressure and temperature, dividing the phase diagram into separate regions
      where the fluid possesses liquidlike and gaslike properties. On the liquidlike
      side the Raman-active vibration increases in frequency linearly as pressure is
      increased, as expected due to the repulsive interaction between adjacent
      molecules. On the gaslike side this competes with the attractive van der Waals
      potential leading the vibration frequency to decrease as pressure is increased.

PMID- 29347718
TI  - Three-body interactions improve contact prediction within direct-coupling
      analysis.
AB  - The prediction of residue contacts in a protein solely from sequence information
      is a promising approach to computational structure prediction. Recent
      developments use statistical or information theoretic methods to extract contact
      information from a multiple sequence alignment. Despite good results, accuracy is
      limited due to usage of two-body interactions within a Potts model. In this paper
      we generalize this approach and propose a Hamiltonian with an additional three
      body interaction term. We derive a mean-field approximation for inference of
      three-body couplings within a Potts model which is fast enough on modern
      computers. Finally, we show that our model has a higher accuracy in predicting
      residue contacts in comparison with the plain two-body-interaction model.

PMID- 29347719
TI  - Effect of polymer network on thermodynamic stability and switching behavior of
      the smectic-C_{alpha}^{*} phase.
AB  - A polymer-stabilized liquid crystal based on 4^{'}-(octyloxy)biphenyl-4
      carboxylate 2-fluoro-4-((octyl-2-yloxy)carbonyl)phenyl (D16) and 1,6 hexanediol
      diacrylate as a monomer was prepared by in situ photopolymerization. The selected
      antiferroelectric liquid crystal contains a fast-switching smectic C_{alpha}^{*}
      phase (SmC_{alpha}^{*}), and the influence of the polymer network on the
      thermodynamic stability of this phase and its switching behavior under applying
      time-dependent electric field were studied. Using dielectric spectroscopy and
      polarizing microscopy, the liquid crystal materials were characterized, and
      subsequently with the use of the reversal current method (RCM) the current
      response, especially from the SmC_{alpha}^{*} phase was carefully analyzed. The
      current response is complex and also depends on the neighboring liquid crystal
      phases. In the liquid crystal-polymer system, as well as in the liquid crystal
      monomer mixture, a significant shift of the temperature range of the
      SmC_{alpha}^{*} phase toward lower temperatures was observed; however, the
      thermodynamic instability related to the transformation to the crystalline phase
      was also noted and characterized. Because of the fuzzy phase transitions detected
      in the liquid crystal-polymer system by dielectric spectroscopy and also because
      of the lack of the characteristic dielectric signature of SmC_{alpha}^{*} after
      polymerization, we proposed the use of the RCM, as a complementary one, to
      identify the SmC_{alpha}^{*} phase even in such complex materials.

PMID- 29347720
TI  - Extreme events in the forced Lienard system.
AB  - We observe extremely large amplitude intermittent spikings in a dynamical
      variable of a periodically forced Lienard-type oscillator and characterize them
      as extreme events, which are rare, but recurrent and larger in amplitude than a
      threshold. The extreme events occur via two processes, an interior crisis and
      intermittency. The probability of occurrence of the events shows a long-tail
      distribution in both the cases. We provide evidence of the extreme events in an
      experiment using an electronic analog circuit of the Lienard oscillator that
      shows good agreement with our numerical results.

PMID- 29347721
TI  - Direct verification of the fluctuation-dissipation relation in viscously coupled
      oscillators.
AB  - The fluctuation-dissipation relation, a central result in nonequilibrium
      statistical physics, relates equilibrium fluctuations in a system to its linear
      response to external forces. Here we provide a direct experimental verification
      of this relation for viscously coupled oscillators, as realized by a pair of
      optically trapped colloidal particles. A theoretical analysis, in which
      interactions mediated by slow viscous flow are represented by nonlocal friction
      tensors, matches experimental results and reveals a frequency maximum in the
      amplitude of the mutual response which is a sensitive function of the trap
      stiffnesses and the friction tensors. This allows for its location and width to
      be tuned and suggests the utility of the trap setup for accurate two-point
      microrheology.

PMID- 29347722
TI  - Stochastic thermodynamics of periodically driven systems: Fluctuation theorem for
      currents and unification of two classes.
AB  - Periodic driving is used to operate machines that go from standard macroscopic
      engines to small nonequilibrium microsized systems. Two classes of such systems
      are small heat engines driven by periodic temperature variations, and molecular
      pumps driven by external stimuli. Well-known results that are valid for
      nonequilibrium steady states of systems driven by fixed thermodynamic forces,
      instead of an external periodic driving, have been generalized to periodically
      driven heat engines only recently. These results include a general expression for
      entropy production in terms of currents and affinities, and symmetry relations
      for the Onsager coefficients from linear-response theory. For nonequilibrium
      steady states, the Onsager reciprocity relations can be obtained from the more
      general fluctuation theorem for the currents. We prove a fluctuation theorem for
      the currents for periodically driven systems. We show that this fluctuation
      theorem implies a fluctuation dissipation relation, symmetry relations for
      Onsager coefficients, and further relations for nonlinear response coefficients.
      The setup in this paper is more general than previous studies, i.e., our results
      are valid for both heat engines and molecular pumps. The external protocol is
      assumed to be stochastic in our framework, which leads to a particularly
      convenient way to treat periodically driven systems.

PMID- 29347723
TI  - Hierarchical benchmark graphs for testing community detection algorithms.
AB  - Hierarchical organization is an important, prevalent characteristic of complex
      systems; to understand their organization, the study of the underlying (generally
      complex) networks that describe the interactions between their constituents plays
      a central role. Numerous previous works have shown that many real-world networks
      in social, biologic, and technical systems present hierarchical organization,
      often in the form of a hierarchy of community structures. Many artificial
      benchmark graphs have been proposed to test different community detection
      methods, but no benchmark has been developed to thoroughly test the detection of
      hierarchical community structures. In this study, we fill this vacancy by
      extending the Lancichinetti-Fortunato-Radicchi (LFR) ensemble of benchmark
      graphs, adopting the rule of constructing hierarchical networks proposed by
      Ravasz and Barabasi. We employ this benchmark to test three of the most popular
      community detection algorithms and quantify their accuracy using the traditional
      mutual information and the recently introduced hierarchical mutual information.
      The results indicate that the Ravasz-Barabasi-Lancichinetti-Fortunato-Radicchi
      (RB-LFR) benchmark generates a complex hierarchical structure constituting a
      challenging benchmark for the considered community detection methods.

PMID- 29347724
TI  - Dielectric properties of liquid crystalline dimer mixtures exhibiting the nematic
      and twist-bend nematic phases.
AB  - A detailed investigation of the thermal and dielectric properties of a series of
      binary mixtures exhibiting the nematic (N) and twist-bend nematic (N_{TB}) liquid
      crystal phases is presented. The mixtures consist of an achiral, dimeric liquid
      crystal CB7CB, which forms the nematic and twist-bend nematic phases, and a
      calamitic liquid crystal 5CB, which shows the nematic phase. As the concentration
      of the calamitic liquid crystal is increased, the transition temperatures
      decrease linearly, and the width of the nematic phase increases. The enthalpies
      of phase transitions obtained from DSC measurements show that on increasing the
      concentration of 5CB in the binary mixtures, the enthalpy associated with the N
      N_{TB} phase transitions reduces considerably compared to a clear first-order N
      N_{TB} transition in pure CB7CB. The real and imaginary parts of the dielectric
      permittivity are measured as a function of frequency from 100 Hz to 2 MHz in the
      nematic and twist-bend nematic phases in planar and homeotropic devices. A
      significant decrease in the average dielectric permittivity as a function of
      temperature for mixtures forming the N_{TB} phase is observed. Measurements of
      the imaginary part of the dielectric permittivity show a relaxation peak in the
      measured frequency window for all of the mixtures exhibiting the N_{TB} phase.
      The activation energy associated with this relaxation process is calculated and
      is shown to remain constant irrespective of the composition of the mixtures.

PMID- 29347725
TI  - Partition function zeros of the p-state clock model in the complex temperature
      plane.
AB  - We investigate the partition function zeros of the two-dimensional p-state clock
      model in the complex temperature plane by using the Wang-Landau method. For p=5,
      6, 8, and 10, we propose a modified energy representation to enumerate exact
      irregular energy levels for the density of states without any binning artifacts.
      Comparing the leading zeros between different p's, we provide strong evidence
      that the upper transition at p=6 is indeed of the Berezinskii-Kosterlitz-Thouless
      (BKT) type in contrast to the claim of the previous Fisher zero study [Phys. Rev.
      E 80, 042103 (2009)10.1103/PhysRevE.80.042103]. We find that the leading zeros of
      p=6 at the upper transition collapse onto the zero trajectories of the larger p's
      including the XY limit while the finite-size behavior of p=5 differs from the
      converged behavior of p>=6 within the system sizes examined. In addition, we
      argue that the nondivergent specific heat in the BKT transition is responsible
      for the small partition function magnitude that decreases exponentially with
      increasing system size near the leading zero, fundamentally limiting access to
      large systems in search for zeros with an estimator under finite statistical
      fluctuations.

PMID- 29347726
TI  - Deceleration of one-dimensional mixing by discontinuous mappings.
AB  - We present a computational study of a simple one-dimensional map with dynamics
      composed of stretching, permutations of equally sized cells, and diffusion. We
      observe that the combination of the aforementioned dynamics results in eigenmodes
      with long-time exponential decay rates. The decay rate of the eigenmodes is shown
      to be dependent on the choice of permutation and changes nonmonotonically with
      the diffusion coefficient for many of the permutations. The global mixing rate of
      the map M in the limit of vanishing diffusivity approximates well the decay rates
      of the eigenmodes for small diffusivity, however this global mixing rate does not
      bound the rates for all values of the diffusion coefficient. This
      counterintuitively predicts a deceleration in the asymptotic mixing rate with an
      increasing diffusivity rate. The implications of the results on finite time
      mixing are discussed.

PMID- 29347727
TI  - Nonlinear dynamics of a buoyancy-induced turbulent fire.
AB  - We conduct a numerical study on the dynamic behavior of a buoyancy-induced
      turbulent fire from the viewpoints of symbolic dynamics, complex networks, and
      statistical complexity. Here, we consider two classes of entropies: the
      permutation entropy and network entropy in epsilon-recurrence networks, both of
      which evaluate the degree of randomness in the underlying dynamics. These
      entropies enable us to capture the significant changes in the dynamic behavior of
      flow velocity fluctuations. The possible presence of two important dynamics, low
      dimensional deterministic chaos in the near field dominated by the motion of
      large-scale vortices and high-dimensional chaos in the far field forming a well
      developed turbulent plume, is clearly identified by the multiscale complexity
      entropy causality plane.

PMID- 29347728
TI  - Extracting the equation of state of lattice gases from random sequential
      adsorption simulations by means of the Gibbs adsorption isotherm.
AB  - An alternative approach for deriving the equation of state for a two-dimensional
      lattice gas is proposed, based on arguments similar to those used in the
      derivation of the Langmuir-Szyszkowski equation of state for localized
      adsorption. The relationship between surface coverage and excluded area is first
      extracted from random sequential adsorption simulations incorporating surface
      diffusion (RSAD). The adsorption isotherm is then obtained using kinetic
      arguments, and the Gibbs equation gives the relation between surface pressure and
      coverage. Provided surface diffusion is fast enough to ensure internal
      equilibrium within the monolayer during the RSAD simulations, the resulting
      equations of state are very close to the most accurate equivalents obtained by
      cumbersome thermodynamic methods. An internal test of the accuracy of the method
      is obtained by noting that adsorption RSAD simulations starting from an empty
      lattice and desorption simulations starting from a full lattice provide
      convergent upper and lower bounds on the surface pressure.

PMID- 29347729
TI  - Single-cone finite-difference schemes for the (2+1)-dimensional Dirac equation in
      general electromagnetic textures.
AB  - A single-cone finite-difference lattice scheme is developed for the (2+1)
      dimensional Dirac equation in presence of general electromagnetic textures. The
      latter is represented on a (2+1)-dimensional staggered grid using a second-order
      accurate finite difference scheme. A Peierls-Schwinger substitution to the wave
      function is used to introduce the electromagnetic (vector) potential into the
      Dirac equation. Thereby, the single-cone energy dispersion and gauge invariance
      are carried over from the continuum to the lattice formulation. Conservation laws
      and stability properties of the formal scheme are identified by comparison with
      the scheme for zero vector potential. The placement of magnetization terms is
      inferred from consistency with the one for the vector potential. Based on this
      formal scheme, several numerical schemes are proposed and tested. Elementary
      examples for single-fermion transport in the presence of in-plane magnetization
      are given, using material parameters typical for topological insulator surfaces.

PMID- 29347730
TI  - Rigidity-induced scale invariance in polymer ejection from capsid.
AB  - While the dynamics of a fully flexible polymer ejecting a capsid through a
      nanopore has been extensively studied, the ejection dynamics of semiflexible
      polymers has not been properly characterized. Here we report results from
      simulations of ejection dynamics of semiflexible polymers ejecting from spherical
      capsids. Ejections start from strongly confined polymer conformations of constant
      initial monomer density. We find that, unlike for fully flexible polymers, for
      semiflexible polymers the force measured at the pore does not show a direct
      relation to the instantaneous ejection velocity. The cumulative waiting time
      t(s), that is, the time at which a monomer s exits the capsid the last time,
      shows a clear change when increasing the polymer rigidity kappa. The major part
      of an ejecting polymer is driven out of the capsid by internal pressure. At the
      final stage the polymer escapes the capsid by diffusion. For the driven part
      there is a crossover from essentially exponential growth of t with s of the fully
      flexible polymers to a scale-invariant form. In addition, a clear dependence of t
      on polymer length N_{0} was found. These findings combined give the dependence
      t(s)?N_{0}^{0.55}s^{1.33} for the strongly rigid polymers. This crossover in
      dynamics where kappa acts as a control parameter is reminiscent of a phase
      transition. This analogy is further enhanced by our finding a perfect data
      collapse of t for polymers of different N_{0} and any constant kappa.

PMID- 29347731
TI  - Delay-induced wave instabilities in single-species reaction-diffusion systems.
AB  - The Turing (wave) instability is only possible in reaction-diffusion systems with
      more than one (two) components. Motivated by the fact that a time delay increases
      the dimension of a system, we investigate the presence of diffusion-driven
      instabilities in single-species reaction-diffusion systems with delay. The
      stability of arbitrary one-component systems with a single discrete delay, with
      distributed delay, or with a variable delay is systematically analyzed. We show
      that a wave instability can appear from an equilibrium of single-species reaction
      diffusion systems with fluctuating or distributed delay, which is not possible in
      similar systems with constant discrete delay or without delay. More precisely, we
      show by basic analytic arguments and by numerical simulations that fast
      asymmetric delay fluctuations or asymmetrically distributed delays can lead to
      wave instabilities in these systems. Examples, for the resulting traveling waves
      are shown for a Fisher-KPP equation with distributed delay in the reaction term.
      In addition, we have studied diffusion-induced instabilities from homogeneous
      periodic orbits in the same systems with variable delay, where the homogeneous
      periodic orbits are attracting resonant periodic solutions of the system without
      diffusion, i.e., periodic orbits of the Hutchinson equation with time-varying
      delay. If diffusion is introduced, standing waves can emerge whose temporal
      period is equal to the period of the variable delay.

PMID- 29347732
TI  - Population equations for degree-heterogenous neural networks.
AB  - We develop a statistical framework for studying recurrent networks with broad
      distributions of the number of synaptic links per neuron. We treat each group of
      neurons with equal input degree as one population and derive a system of
      equations determining the population-averaged firing rates. The derivation rests
      on an assumption of a large number of neurons and, additionally, an assumption of
      a large number of synapses per neuron. For the case of binary neurons, analytical
      solutions can be constructed, which correspond to steps in the activity versus
      degree space. We apply this theory to networks with degree-correlated topology
      and show that complex, multi-stable regimes can result for increasing
      correlations. Our work is motivated by the recent finding of subnetworks of
      highly active neurons and the fact that these neurons tend to be connected to
      each other with higher probability.

PMID- 29347733
TI  - Lattice Boltzmann model capable of mesoscopic vorticity computation.
AB  - It is well known that standard lattice Boltzmann (LB) models allow the strain
      rate components to be computed mesoscopically (i.e., through the local particle
      distributions) and as such possess a second-order accuracy in strain rate. This
      is one of the appealing features of the lattice Boltzmann method (LBM) which is
      of only second-order accuracy in hydrodynamic velocity itself. However, no known
      LB model can provide the same quality for vorticity and pressure gradients. In
      this paper, we design a multiple-relaxation time LB model on a three-dimensional
      27-discrete-velocity (D3Q27) lattice. A detailed Chapman-Enskog analysis is
      presented to illustrate all the necessary constraints in reproducing the
      isothermal Navier-Stokes equations. The remaining degrees of freedom are
      carefully analyzed to derive a model that accommodates mesoscopic computation of
      all the velocity and pressure gradients from the nonequilibrium moments. This way
      of vorticity calculation naturally ensures a second-order accuracy, which is also
      proven through an asymptotic analysis. We thus show, with enough degrees of
      freedom and appropriate modifications, the mesoscopic vorticity computation can
      be achieved in LBM. The resulting model is then validated in simulations of a
      three-dimensional decaying Taylor-Green flow, a lid-driven cavity flow, and a
      uniform flow passing a fixed sphere. Furthermore, it is shown that the mesoscopic
      vorticity computation can be realized even with single relaxation parameter.

PMID- 29347734
TI  - Electrically induced structure transition in nematic liquid crystal droplets with
      conical boundary conditions.
AB  - Polymer-dispersed liquid crystal composites have been a focus of study for a long
      time for their unique electro-optical properties and manufacturing by "bottom-up"
      techniques at large scales. In this paper, nematic liquid crystal oblate droplets
      with conical boundary conditions (CBCs) under the action of electric field were
      studied by computer simulations and polarized optical microscopy. Droplets with
      CBCs were shown to prefer an axial-bipolar structure, which combines a pair of
      boojums and circular disclinations on a surface. In contrast to droplets with
      degenerate planar boundary conditions (PBCs), hybridization of the two structure
      types in droplets with CBCs leads to a two-minima energy profile, resulting in an
      abrupt structure transition and bistable behavior of the system. The nature of
      the low-energy barrier in droplets with CBCs makes it highly sensitive to
      external stimuli, such as electric or magnetic fields, temperature, and light. In
      particular, the value of the electric field of the structure reorientation in
      droplets with CBCs was found to be a few times smaller than the one for droplets
      with PBCs, and the droplet state remained stable after switching off the voltage.

PMID- 29347735
TI  - Spreading of nonmotile bacteria on a hard agar plate: Comparison between agent
      based and stochastic simulations.
AB  - We study spreading of a nonmotile bacteria colony on a hard agar plate by using
      agent-based and continuum models. We show that the spreading dynamics depends on
      the initial nutrient concentration, the motility, and the inherent demographic
      noise. Population fluctuations are inherent in an agent-based model, whereas for
      the continuum model we model them by using a stochastic Langevin equation. We
      show that the intrinsic population fluctuations coupled with nonlinear
      diffusivity lead to a transition from a diffusion limited aggregation type of
      morphology to an Eden-like morphology on decreasing the initial nutrient
      concentration.

PMID- 29347736
TI  - Locality of interactions for planar memristive circuits.
AB  - The dynamics of purely memristive circuits has been shown to depend on a
      projection operator which expresses the Kirchhoff constraints, is naturally non
      local in nature, and does represent the interaction between memristors. In the
      present paper we show that for the case of planar circuits, for which a
      meaningful Hamming distance can be defined, the elements of such projector can be
      bounded by exponentially decreasing functions of the distance. We provide a
      geometrical interpretation of the projector elements in terms of determinants of
      Dirichlet Laplacian of the dual circuit. For the case of linearized dynamics of
      the circuit for which a solution is known, this can be shown to provide a light
      cone bound for the interaction between memristors. This result establishes a
      finite speed of propagation of signals across the network, despite the non-local
      nature of the system.

PMID- 29347737
TI  - Influence of topographically patterned angled guidelines on directed self
      assembly of block copolymers.
AB  - Single chain in mean-field Monte Carlo simulations were employed to study the
      self-assembly of block copolymers (BCP) in thin films that use trapezoidal
      guidelines to direct the orientation and alignment of lamellar patterns. The
      present study explored the influence of sidewall interactions and geometry of the
      trapezoidal guidelines on the self-assembly of perpendicularly oriented lamellar
      morphologies. When both the sidewall and the top surface exhibit preferential
      interactions to the same block of the BCP, trapezoidal guidelines with
      intermediate taper angles were found to result in less defective perpendicularly
      orientated morphologies. Similarly, when the sidewall and top surface are
      preferential to distinct blocks of the BCP, intermediate tapering angles were
      found to be optimal in promoting defect free structures. Such results are
      rationalized based on the energetics arising in the formation of perpendicularly
      oriented lamella on patterned substrates.

PMID- 29347738
TI  - Finite-range Coulomb gas models of banded random matrices and quantum kicked
      rotors.
AB  - Dyson demonstrated an equivalence between infinite-range Coulomb gas models and
      classical random matrix ensembles for the study of eigenvalue statistics. We
      introduce finite-range Coulomb gas (FRCG) models via a Brownian matrix process,
      and study them analytically and by Monte Carlo simulations. These models yield
      new universality classes, and provide a theoretical framework for the study of
      banded random matrices (BRMs) and quantum kicked rotors (QKRs). We demonstrate
      that, for a BRM of bandwidth b and a QKR of chaos parameter alpha, the
      appropriate FRCG model has the effective range d=b^{2}/N=alpha^{2}/N, for large N
      matrix dimensionality. As d increases, there is a transition from Poisson to
      classical random matrix statistics.

PMID- 29347739
TI  - Fluid-driven fracture propagation in heterogeneous media: Probability
      distributions of fracture trajectories.
AB  - Hydraulic fracture trajectories in rocks and other materials are highly affected
      by spatial heterogeneity in their mechanical properties. Understanding the
      complexity and structure of fluid-driven fractures and their deviation from the
      predictions of homogenized theories is a practical problem in engineering and
      geoscience. We conduct a Monte Carlo simulation study to characterize the
      influence of heterogeneous mechanical properties on the trajectories of hydraulic
      fractures propagating in elastic media. We generate a large number of random
      fields of mechanical properties and simulate pressure-driven fracture propagation
      using a phase-field model. We model the mechanical response of the material as
      that of an elastic isotropic material with heterogeneous Young modulus and
      Griffith energy release rate, assuming that fractures propagate in the toughness
      dominated regime. Our study shows that the variance and the spatial covariance of
      the mechanical properties are controlling factors in the tortuousness of the
      fracture paths. We characterize the deviation of fracture paths from the
      homogenous case statistically, and conclude that the maximum deviation grows
      linearly with the distance from the injection point. Additionally, fracture path
      deviations seem to be normally distributed, suggesting that fracture propagation
      in the toughness-dominated regime may be described as a random walk.

PMID- 29347740
TI  - Evolving power grids with self-organized intermittent strain releases: An analogy
      with sandpile models and earthquakes.
AB  - The stability of powergrid is crucial since its disruption affects systems
      ranging from street lightings to hospital life-support systems. While short-term
      dynamics of single-event cascading failures have been extensively studied, less
      is understood on the long-term evolution and self-organization of powergrids. In
      this paper, we introduce a simple model of evolving powergrid and establish its
      connection with the sandpile model and earthquakes, i.e., self-organized systems
      with intermittent strain releases. Various aspects during its self-organization
      are examined, including blackout magnitudes, their interevent waiting time, the
      predictability of large blackouts, as well as the spatiotemporal rescaling of
      blackout data. We examined the self-organized strain releases on simulated
      networks as well as the IEEE 118-bus system, and we show that both simulated and
      empirical blackout waiting times can be rescaled in space and time similarly to
      those observed between earthquakes. Finally, we suggested proactive maintenance
      strategies to drive the powergrids away from self-organization to suppress large
      blackouts.

PMID- 29347741
TI  - Perturbation theory for water with an associating reference fluid.
AB  - The theoretical description of the thermodynamics of water is challenged by the
      structural transition towards tetrahedral symmetry at ambient conditions. As
      perturbation theories typically assume a spherically symmetric reference fluid,
      they are incapable of accurately describing the liquid properties of water at
      ambient conditions. In this paper we address this problem by introducing the
      concept of an associated reference perturbation theory (APT). In APT we treat the
      reference fluid as an associating hard sphere fluid which transitions to
      tetrahedral symmetry in the fully hydrogen bonded limit. We calculate this
      transition in a theoretically self-consistent manner without appealing to
      molecular simulations. This associated reference provides the reference fluid for
      a second order Barker-Henderson perturbative treatment of the long-range
      attractions. We demonstrate that this approach gives a significantly improved
      description of water as compared to standard perturbation theories.

PMID- 29347742
TI  - Exact solution of the hidden Markov processes.
AB  - We write a master equation for the distributions related to hidden Markov
      processes (HMPs) and solve it using a functional equation. Thus the solution of
      HMPs is mapped exactly to the solution of the functional equation. For a general
      case the latter can be solved only numerically. We derive an exact expression for
      the entropy of HMPs. Our expression for the entropy is an alternative to the ones
      given before by the solution of integral equations. The exact solution is
      possible because actually the model can be considered as a generalized random
      walk on a one-dimensional strip. While we give the solution for the two second
      order matrices, our solution can be easily generalized for the L values of the
      Markov process and M values of observables: We should be able to solve a system
      of L functional equations in the space of dimension M-1.

PMID- 29347743
TI  - Flat bands and compactons in mechanical lattices.
AB  - Local configurational symmetry in lattice structures may give rise to stationary,
      compact solutions, even in the absence of disorder and nonlinearity. These
      compact solutions are related to the existence of flat dispersion curves (bands).
      Nonlinearity can destabilize such compactons. One common flat-band-generating
      system is the one-dimensional cross-stitch model, in which compactons were shown
      to exist for the photonic lattice with Kerr nonlinearity. The compactons exist
      there already in the linear regime and are not generally destructed by that
      nonlinearity. Smooth nonlinearity of this kind does not permit performing
      complete stability analysis for this chain. We consider a discrete mechanical
      system with flat dispersion bands, in which the nonlinearity exists due to impact
      constraints. In this case, one can use the concept of the saltation matrix for
      the analytic construction of the monodromy matrix. Besides, we consider a smooth
      nonlinear lattice with linearly connected massless boxes, each containing two
      symmetric anharmonic oscillators. In this model, the flat bands and discrete
      compactons also readily emerge. This system also permits performing comprehensive
      stability analysis, at least in the anticontinuum limit, due to the reduced
      number of degrees of freedom. In both systems, there exist two types of
      localization. The first one is the complete localization, and the second one is
      the more common exponential localization. The latter type is associated with
      discrete breathers (DBs). Two principal mechanisms for the loss of stability are
      revealed. The first one is the possible internal instability of the symmetric
      and/or antisymmetric solution in the individual unit cell of the chain. One can
      interpret this instability pattern as internal resonance between the compacton
      and the DB. The other mechanism is global instability related to resonance of the
      stationary solution with the propagation frequencies. Different instability
      mechanisms lead to different bifurcations at the stability threshold.

PMID- 29347744
TI  - Quantum fluctuations of entropy production for fermionic systems in the Landauer
      Buttiker state.
AB  - The quantum fluctuations of the entropy production for fermionic systems in the
      Landauer-Buttiker nonequilibrium steady state are investigated. The probability
      distribution, governing these fluctuations, is explicitly derived by means of
      quantum field theory methods and analyzed in the zero frequency limit. It turns
      out that microscopic processes with positive, vanishing and negative entropy
      production occur in the system with nonvanishing probability. In spite of this
      fact, we show that all odd moments (in particular, the mean value of the entropy
      production) of the above distribution are non-negative. This result extends the
      second principle of thermodynamics to the quantum fluctuations of the entropy
      production in the Landauer-Buttiker state. The effect of the time reversal is
      also discussed.

PMID- 29347746
TI  - Topological defects in two-dimensional orientation-field models for grain growth.
AB  - Standard two-dimensional orientation-field-based phase-field models rely on a
      continuous scalar field to represent crystallographic orientation. The
      corresponding order parameter space is the unit circle, which is not simply
      connected. This topological property has important consequences for the resulting
      multigrain structures: (i) trijunctions may be singular; (ii) for each pair of
      grains there exist two different grain boundary solutions that cannot
      continuously transform to one another; (iii) if both solutions appear along a
      grain boundary, a topologically stable, singular point defect must exist between
      them. While (i) can be interpreted in the classical picture of grain boundaries,
      (ii) and therefore (iii) cannot. In addition, singularities cause difficulties,
      such as lattice pinning in numerical simulations. To overcome these problems, we
      propose two formulations of the model. The first is based on a three-component
      unit vector field, while in the second we utilize a two-component vector field
      with an additional potential. In both cases, the additional degree of freedom
      introduced makes the order parameter space simply connected, which removes the
      topological stability of these defects.

PMID- 29347745
TI  - Multiplexing topologies and time scales: The gains and losses of synchrony.
AB  - Inspired by the recent interest in collective dynamics of biological neural
      networks immersed in the glial cell medium, we investigate the frequency and
      phase order, i.e., Kuramoto type of synchronization in a multiplex two-layer
      network of phase oscillators of different time scales and topologies. One of them
      has a long-range connectivity, exemplified by the Erdos-Renyi random network, and
      supports both kinds of synchrony. The other is a locally coupled two-dimensional
      lattice that can reach frequency synchronization but lacks phase order.
      Drastically different layer frequencies disentangle intra- and interlayer
      synchronization. We find that an indirect but sufficiently strong coupling
      through the regular layer can induce both phase order in the originally
      nonsynchronized random layer and global order, even when an isolated regular
      layer does not manifest it in principle. At the same time, the route to global
      synchronization is complex: an initial onset of (partial) synchrony in the
      regular layer, when its intra- and interlayer coupling is increased, provokes the
      loss of synchrony even in the originally synchronized random layer. Ultimately, a
      developed asynchronous dynamics in both layers is abruptly taken over by the
      global synchrony of both kinds.

PMID- 29347747
TI  - Dynamical transition on the periodic Lorentz gas: Stochastic and deterministic
      approaches.
AB  - The effect of dynamical properties of the periodic Lorentz gas on the
      autocorrelation function and diffusion coefficient are investigated in various
      geometric transitions between billiards without horizon and infinite horizon.
      Numerical simulations are performed using a double square lattice which permits
      us to isolate different types of corridors and to describe the individual effects
      of each corridor. The results are compared with a stochastic model based on a
      escape-rate formalism which reveals the sensibility of the diffusion coefficient
      and clarifies the role of the open corridors mechanism on the dynamical
      transitions.

PMID- 29347748
TI  - Asymmetric couplings enhance the transition from chimera state to
      synchronization.
AB  - Chimera state has been well studied recently, but little attention has been paid
      to its transition to synchronization. We study this topic here by considering two
      groups of adaptively coupled Kuramoto oscillators. By searching the final states
      of different initial conditions, we find that the system can easily show a
      chimera state with robustness to initial conditions, in contrast to the sensitive
      dependence of chimera state on initial conditions in previous studies. Further,
      we show that, in the case of symmetric couplings, the behaviors of the two groups
      are always complementary to each other, i.e., robustness of chimera state, except
      a small basin of synchronization. Interestingly, we reveal that the basin of
      synchronization will be significantly increased when either the coupling of inner
      groups or that of intergroups are asymmetric. This transition from the attractor
      of chimera state to the attractor of synchronization is closely related to both
      the phase delay and the asymmetric degree of coupling strengths, resulting in a
      diversity of attractor's patterns. A theory based on the Ott-Antonsen ansatz is
      given to explain the numerical simulations. This finding may be meaningful for
      the control of competition between two attractors in biological systems, such as
      the cardiac rhythm and ventricular fibrillation, etc.

PMID- 29347749
TI  - Confined sandpile in two dimensions: Percolation and singular diffusion.
AB  - We investigate the properties of a two-state sandpile model subjected to a
      confining potential in two dimensions. From the microdynamical description, we
      derive a diffusion equation, and find a stationary solution for the case of a
      parabolic confining potential. By studying the systems at different confining
      conditions, we observe two scale-invariant regimes. At a given confining
      potential strength, the cluster size distribution takes the form of a power law.
      This regime corresponds to the situation in which the density at the center of
      the system approaches the critical percolation threshold. The analysis of the
      fractal dimension of the largest cluster frontier provides evidence that this
      regime is reminiscent of gradient percolation. By increasing further the
      confining potential, most of the particles coalesce in a giant cluster, and we
      observe a regime where the jump size distribution takes the form of a power law.
      The onset of this second regime is signaled by a maximum in the fluctuation of
      energy.

PMID- 29347750
TI  - Benchmarking of three-dimensional multicomponent lattice Boltzmann equation.
AB  - We present a challenging validation of phase field multicomponent lattice
      Boltzmann equation (MCLBE) simulation against the Re=0 Stokes flow regime Taylor
      Einstein theory of dilute suspension viscosity. By applying a number of recent
      advances in the understanding and the elimination of the interfacial microcurrent
      artefact, extending to a three-dimensional class of stability-enhancing multiple
      relaxation time collision models (which require no explicit collision matrix,
      note) and developing new interfacial interpolation schemes, we are able to obtain
      data that show that MCLBE may be applied in new flow regimes. Our data represent
      one of the most stringent tests yet attempted on LBE-one which received wisdom
      would preclude on grounds of overwhelming artefact flow.

PMID- 29347751
TI  - Surface deformation during an action potential in pearled cells.
AB  - Electric pulses in biological cells (action potentials) have been reported to be
      accompanied by a propagating cell-surface deformation with a nanoscale amplitude.
      Typically, this cell surface is covered by external layers of polymer material
      (extracellular matrix, cell wall material, etc.). It was recently demonstrated in
      excitable plant cells (Chara braunii) that the rigid external layer (cell wall)
      hinders the underlying deformation. When the cell membrane was separated from the
      cell wall by osmosis, a mechanical deformation, in the micrometer range, was
      observed upon excitation of the cell. The underlying mechanism of this mechanical
      pulse has, to date, remained elusive. Herein we report that Chara cells can
      undergo a pearling instability, and when the pearled fragments were excited even
      larger and more regular cell shape changes were observed (~10-100MUm in
      amplitude). These transient cellular deformations were captured by a curvature
      model that is based on three parameters: surface tension, bending rigidity, and
      pressure difference across the surface. In this paper these parameters are
      extracted by curve-fitting to the experimental cellular shapes at rest and during
      excitation. This is a necessary step to identify the mechanical parameters that
      change during an action potential.

PMID- 29347752
TI  - Noise-driven current reversal and stabilization in the tilted ratchet potential
      subject to tempered stable Levy noise.
AB  - We consider motion of a particle in a one-dimensional tilted ratchet potential
      subject to two-sided tempered stable Levy noise characterized by strength Omega,
      fractional index alpha, skew theta, and tempering lambda. We derive analytic
      solutions to the corresponding Fokker-Planck Levy equations for the probability
      density. Due to the periodicity of the potential, we carry out reduction to a
      compact domain and solve for the analog of steady-state solutions which we
      represent as wrapped probability density functions. By solving for the expected
      value of the current associated with the particle motion, we are able to
      determine thresholds for metastability of the system, namely when the particle
      stabilizes in a well of the potential and when the particle is in motion, for
      example as a consequence of the tilt of the potential. Because the noise may be
      asymmetric, we examine the relationship between skew of the noise and the tilt of
      the potential. With tempering, we find two remarkable regimes where the current
      may be reversed in a direction opposite to the tilt or where the particle may be
      stabilized in a well in circumstances where deterministically it should flow with
      the tilt.

PMID- 29347753
TI  - Consistent forcing scheme in the cascaded lattice Boltzmann method.
AB  - In this paper, we give an alternative derivation for the cascaded lattice
      Boltzmann method (CLBM) within a general multiple-relaxation-time (MRT) framework
      by introducing a shift matrix. When the shift matrix is a unit matrix, the CLBM
      degrades into an MRT LBM. Based on this, a consistent forcing scheme is developed
      for the CLBM. The consistency of the nonslip rule, the second-order convergence
      rate in space, and the property of isotropy for the consistent forcing scheme is
      demonstrated through numerical simulations of several canonical problems. Several
      existing forcing schemes previously used in the CLBM are also examined. The study
      clarifies the relation between MRT LBM and CLBM under a general framework.

PMID- 29347754
TI  - Theory of corticothalamic brain activity in a spherical geometry: Spectra,
      coherence, and correlation.
AB  - Corticothalamic neural field theory is applied to a spherical geometry to better
      model neural activity in the human brain and is also compared with planar
      approximations. The frequency power spectrum, correlation, and coherence
      functions are computed analytically and numerically. The effects of cortical
      boundary conditions and resulting modal aspects of spherical corticothalamic
      dynamics are explored, showing that the results of spherical and finite planar
      geometries converge to those for the infinite planar geometry in the limit of
      large brain size. Estimates are made of the point at which modal series can be
      truncated and it is found that for physiologically plausible parameters only the
      lowest few spatial eigenmodes are needed for an accurate representation of
      macroscopic brain activity. A difference between the geometries is that there is
      a low-frequency 1/f spectrum in the infinite planar geometry, whereas in the
      spherical geometry it is 1/f^{2}. Another difference is that the alpha peak in
      the spherical geometry is sharper and stronger than in the planar geometry.
      Cortical modal effects can lead to a double alpha peak structure in the power
      spectrum, although the main determinant of the alpha peak is corticothalamic
      feedback. In the spherical geometry, the cross spectrum between two points is
      found to only depend on their relative distance apart. At small spatial
      separations the low-frequency cross spectrum is stronger than for an infinite
      planar geometry and the alpha peak is sharper and stronger due to the
      partitioning of the energy into discrete modes. In the spherical geometry, the
      coherence function between points decays monotonically as their separation
      increases at a fixed frequency, but persists further at resonant frequencies. The
      correlation between two points is found to be positive, regardless of the time
      lag and spatial separation, but decays monotonically as the separation increases
      at fixed time lag. At fixed distance the correlation has peaks at multiples of
      the period of the dominant frequency of system activity.

PMID- 29347755
TI  - Transition to synchrony in degree-frequency correlated Sakaguchi-Kuramoto model.
AB  - We investigate transition to synchrony in degree-frequency correlated Sakaguchi
      Kuramoto (SK) model on complex networks both analytically and numerically. We
      analytically derive self-consistent equations for group angular velocity and
      order parameter for the model in the thermodynamic limit. Using the self
      consistent equations we investigate transition to synchronization in SK model on
      uncorrelated scale-free (SF) and Erdos-Renyi (ER) networks in detail. Depending
      on the degree distribution exponent (gamma) of SF networks and phase-frustration
      parameter, the population undergoes from first-order transition [explosive
      synchronization (ES)] to second-order transition and vice versa. In ER networks
      transition is always second order irrespective of the values of the phase-lag
      parameter. We observe that the critical coupling strength for the onset of
      synchronization is decreased by phase-frustration parameter in case of SF network
      where as in ER network, the phase-frustration delays the onset of
      synchronization. Extensive numerical simulations using SF and ER networks are
      performed to validate the analytical results. An analytical expression of
      critical coupling strength for the onset of synchronization is also derived from
      the self-consistent equations considering the vanishing order parameter limit.

PMID- 29347756
TI  - Improved understanding of the acoustophoretic focusing of dense suspensions in a
      microchannel.
AB  - We provide improved understanding of acoustophoretic focusing of a dense
      suspension (volume fraction phi>10%) in a microchannel subjected to an acoustic
      standing wave using a proposed theoretical model and experiments. The model is
      based on the theory of interacting continua and utilizes a momentum transport
      equation for the mixture, continuity equation, and transport equation for the
      solid phase. The model demonstrates the interplay between acoustic radiation and
      shear-induced diffusion (SID) forces that is critical in the focusing of dense
      suspensions. The shear-induced particle migration model of Leighton and Acrivos,
      coupled with the acoustic radiation force, is employed to simulate the continuum
      behavior of particles. In the literature, various closures for the diffusion
      coefficient D_{phi}^{*} are available for rigid spheres at high concentrations
      and nonspherical deformable particles [e.g., red blood cells (RBCs)] at low
      concentrations. Here we propose a closure for D_{phi}^{*} for dense suspension of
      RBCs and validate the proposed model with experimental data. While the available
      closures for D_{phi}^{*} fail to predict the acoustic focusing of a dense
      suspension of nonspherical deformable particles like RBCs, the predictions of the
      proposed model match experimental data within 15%. Both the model and experiments
      reveal a competition between acoustic radiation and SID forces that gives rise to
      an equilibrium width w^{*} of a focused stream of particles at some distance
      L_{eq}^{*} along the flow direction. Using different shear rates, acoustic energy
      densities, and particle concentrations, we show that the equilibrium width is
      governed by Peclet number Pe and Strouhal number Stasw^{*}=1.4(PeSt)^{-0.5} while
      the length required to obtain the equilibrium-focused width depends on St as
      L_{eq}^{*}=3.8/(St)^{0.6}. The proposed model and correlations would find
      significance in the design of microchannels for acoustic focusing of dense
      suspensions such as undiluted blood.

PMID- 29347757
TI  - Evolution of the pore size distribution in sheared binary glasses.
AB  - Molecular dynamics simulations are carried out to investigate mechanical
      properties and porous structure of binary glasses subjected to steady shear. The
      model vitreous systems were prepared via thermal quench at constant volume to a
      temperature well below the glass transition. The quiescent samples are
      characterized by a relatively narrow pore size distribution whose mean size is
      larger at lower glass densities. We find that in the linear regime of
      deformation, the shear modulus is a strong function of porosity, and the
      individual pores become slightly stretched while their structural topology
      remains unaffected. By contrast, with further increasing strain, the shear stress
      saturates to a density-dependent plateau value, which is accompanied by pore
      coalescence and a gradual development of a broader pore size distribution with a
      discrete set of peaks at large length scales.

PMID- 29347758
TI  - Turbulent diffusion of chemically reacting flows: Theory and numerical
      simulations.
AB  - The theory of turbulent diffusion of chemically reacting gaseous admixtures
      developed previously [T. Elperin et al., Phys. Rev. E 90, 053001 (2014)PLEEE81539
      375510.1103/PhysRevE.90.053001] is generalized for large yet finite Reynolds
      numbers and the dependence of turbulent diffusion coefficient on two parameters,
      the Reynolds number and Damkohler number (which characterizes a ratio of
      turbulent and reaction time scales), is obtained. Three-dimensional direct
      numerical simulations (DNSs) of a finite-thickness reaction wave for the first
      order chemical reactions propagating in forced, homogeneous, isotropic, and
      incompressible turbulence are performed to validate the theoretically predicted
      effect of chemical reactions on turbulent diffusion. It is shown that the
      obtained DNS results are in good agreement with the developed theory.

PMID- 29347759
TI  - Isochoric, isobaric, and ultrafast conductivities of aluminum, lithium, and
      carbon in the warm dense matter regime.
AB  - We study the conductivities sigma of (i) the equilibrium isochoric state
      sigma_{is}, (ii) the equilibrium isobaric state sigma_{ib}, and also the (iii)
      nonequilibrium ultrafast matter state sigma_{uf} with the ion temperature T_{i}
      less than the electron temperature T_{e}. Aluminum, lithium, and carbon are
      considered, being increasingly complex warm dense matter systems, with carbon
      having transient covalent bonds. First-principles calculations, i.e., neutral
      pseudoatom (NPA) calculations and density-functional theory (DFT) with molecular
      dynamics (MD) simulations, are compared where possible with experimental data to
      characterize sigma_{ic}, sigma_{ib}, and sigma_{uf}. The NPA sigma_{ib} is
      closest to the available experimental data when compared to results from DFT with
      MD simulations, where simulations of about 64-125 atoms are typically used. The
      published conductivities for Li are reviewed and the value at a temperature of
      4.5 eV is examined using supporting x-ray Thomson-scattering calculations. A
      physical picture of the variations of sigma with temperature and density
      applicable to these materials is given. The insensitivity of sigma to T_{e} below
      10 eV for carbon, compared to Al and Li, is clarified.

PMID- 29347760
TI  - Anomalies in the equilibrium and nonequilibrium properties of correlated ions in
      complex molecular environments.
AB  - Emergent statistical attributes, and therefore the equations of state, of an
      assembly of interacting charge carriers embedded within a complex molecular
      environment frequently exhibit a variety of anomalies, particularly in the high
      density (equivalently, the concentration) regime, which are not well understood,
      because they do not fall under the low-concentration phenomenologies of Debye
      Huckel-Onsager and Poisson-Nernst-Planck, including their variants. To go beyond,
      we here use physical concepts and mathematical tools from quantum scattering
      theory, transport theory with the Stosszahlansatz of Boltzmann, and classical
      electrodynamics (Lorentz gauge) and obtain analytical expressions both for the
      average and the frequency-wave vector-dependent longitudinal and transverse
      current densities, diffusion coefficient, and the charge density, and therefore
      the analytical expressions for (a) the chemical potential, activity coefficient,
      and the equivalent conductivity for strong electrolytes and (b) the current
      voltage characteristics for ion-transport processes in complex molecular
      environments. Using a method analogous to the notion of Debye length and thence
      the electrical double layer, we here identify a pair of characteristic length
      scales (longitudinal and the transverse), which, being wave vector and frequency
      dependent, manifestly exhibit nontrivial fluctuations in space-time. As a
      unifying theme, we advance a quantity (inverse length dimension), g_{scat}^{(a)},
      which embodies all dynamical interactions, through various quantum scattering
      lengths, relevant to molecular species a, and the analytical behavior which helps
      us to rationalize the properties of strong electrolytes, including anomalies, in
      all concentration regimes. As an example, the behavior of g_{scat}^{(a)} in the
      high-concentration regime explains the anomalous increase of the Debye length
      with concentration, as seen in a recent experiment on electrolyte solutions. We
      also put forth an extension of the standard diffusion equation, which manifestly
      incorporates the effects arising from the underlying microscopic collisions among
      constituent molecular species. Furthermore, we show a nontrivial connection
      between the current-voltage characteristics of electrolyte solutions and the
      Landauer's approach to electrical conduction in mesoscopic solids and thereby
      establish a definite conceptual bridge between the two disjoint subjects. For
      numerical insight, we present results on the aqueous solution of KCl as an
      example of strong electrolyte, and the transport (conduction as well as
      diffusion) of K^{+} ions in water, as an example of ion transport across the
      voltage-gated channels in biological cells.

PMID- 29347761
TI  - Analytical mesoscale modeling of aeolian sand transport.
AB  - The mesoscale structure of aeolian sand transport determines a variety of natural
      phenomena studied in planetary and Earth science. We analyze it theoretically
      beyond the mean-field level, based on the grain-scale transport kinetics and
      splash statistics. A coarse-grained analytical model is proposed and verified by
      numerical simulations resolving individual grain trajectories. The predicted
      height-resolved sand flux and other important characteristics of the aeolian
      transport layer agree remarkably well with a comprehensive compilation of field
      and wind-tunnel data, suggesting that the model robustly captures the essential
      mesoscale physics. By comparing the predicted saturation length with field data
      for the minimum sand-dune size, we elucidate the importance of intermittent
      turbulent wind fluctuations for field measurements and reconcile conflicting
      previous models for this most enigmatic emergent aeolian scale.

PMID- 29347762
TI  - Modified mean-field theory of the magnetic properties of concentrated, high
      susceptibility, polydisperse ferrofluids.
AB  - The effects of particle-size polydispersity on the magnetostatic properties of
      concentrated ferrofluids are studied using theory and computer simulation. The
      second-order modified mean-field (MMF2) theory of Ivanov and Kuznetsova [Phys.
      Rev. E 64, 041405 (2001)1063-651X10.1103/PhysRevE.64.041405] has been extended by
      calculating additional terms of higher order in the dipolar coupling constant in
      the expansions of the initial magnetic susceptibility and the magnetization
      curve. The theoretical predictions have been tested rigorously against results
      from Monte Carlo simulations of model monodisperse, bidisperse, and highly
      polydisperse ferrofluids. Comparisons have been made between systems with the
      same Langevin susceptibility and the same saturation magnetization. In all cases,
      the new theoretical magnetization curve shows better agreement with simulation
      data than does the MMF2 theory. As for the initial susceptibility, MMF2 theory is
      most accurate for the monodisperse model, while the new theory works best for
      polydisperse systems with a significant proportion of large particles. These
      results are important for the analysis and characterization of recently
      synthesized polydisperse ferrofluids with record-breaking values of the initial
      magnetic susceptibility.

PMID- 29347763
TI  - Rayleigh-Taylor instability and vortex rings in coupled Gross-Pitaevskii
      equations.
AB  - The Rayleigh-Taylor instability is a gravitational instability in two fluids
      where the heavier fluid is set over the lighter fluid. The instability occurs
      both in classical fluids and quantum fluids. We numerically study the Rayleigh
      Taylor instability using coupled Gross-Pitaevskii equations for two-component
      Bose-Einstein condensates. We carry out numerical simulations that the heavier
      component is set in a torus initially which is surrounded by the lighter
      component. When the torus falls, the Rayleigh-Taylor instability develops and a
      sagging pattern appears. This instability is investigated for the two cases with
      and without a vortex ring inside the torus. We find that a vortex ring suppresses
      the instability when the radius of the torus is small.

PMID- 29347764
TI  - Exact relations for energy transfer in self-gravitating isothermal turbulence.
AB  - Self-gravitating isothermal supersonic turbulence is analyzed in the asymptotic
      limit of large Reynolds numbers. Based on the inviscid invariance of total
      energy, an exact relation is derived for homogeneous (not necessarily isotropic)
      turbulence. A modified definition for the two-point energy correlation functions
      is used to comply with the requirement of detailed energy equipartition in the
      acoustic limit. In contrast to the previous relations (S. Galtier and S.
      Banerjee, Phys. Rev. Lett. 107, 134501 (2011)PRLTAO0031
      900710.1103/PhysRevLett.107.134501; S. Banerjee and S. Galtier, Phys. Rev. E 87,
      013019 (2013)PLEEE81539-375510.1103/PhysRevE.87.013019), the current exact
      relation shows that the pressure dilatation terms play practically no role in the
      energy cascade. Both the flux and source terms are written in terms of two-point
      differences. Sources enter the relation in a form of mixed second-order structure
      functions. Unlike the kinetic and thermodynamic potential energies, the
      gravitational contribution is absent from the flux term. An estimate shows that,
      for the isotropic case, the correlation between density and gravitational
      acceleration may play an important role in modifying the energy transfer in self
      gravitating turbulence. The exact relation is also written in an alternative form
      in terms of two-point correlation functions, which is then used to describe scale
      by-scale energy budget in spectral space.

PMID- 29347765
TI  - Laser-excited motion of liquid crystals confined in a microsized volume with a
      free surface.
AB  - The thermally excited vortical flow in a microsized liquid crystal (LC) volume
      with a free LC-air interface has been investigated theoretically based on the
      nonlinear extension of the Ericksen-Leslie theory, with accounting the entropy
      balance equation. Analysis of the numerical results show that due to interaction
      between the gradients of the director field ?n[over ] and temperature field ?T,
      caused by the focused heating, the thermally excited vortical fluid flow is
      maintained in the vicinity of the heat source. Calculations show that the
      magnitude and direction of the velocity field v, as well as the height of the LC
      air interface are influenced by the depth of the heat penetration in the LC
      volume. It has been shown that there is the point in the vicinity of the LC-air
      interface where the thermally excited vortical flow changes the direction from
      anticlockwise to clockwise.

PMID- 29347766
TI  - Correlations in eigenfunctions of quantum chaotic systems with sparse Hamiltonian
      matrices.
AB  - In most realistic models for quantum chaotic systems, the Hamiltonian matrices in
      unperturbed bases have a sparse structure. We study correlations in
      eigenfunctions of such systems and derive explicit expressions for some of the
      correlation functions with respect to energy. The analytical results are tested
      in several models by numerical simulations. Some applications are discussed for a
      relation between transition probabilities and for expectation values of some
      local observables.

PMID- 29347767
TI  - Sampling of temporal networks: Methods and biases.
AB  - Temporal networks have been increasingly used to model a diversity of systems
      that evolve in time; for example, human contact structures over which dynamic
      processes such as epidemics take place. A fundamental aspect of real-life
      networks is that they are sampled within temporal and spatial frames.
      Furthermore, one might wish to subsample networks to reduce their size for better
      visualization or to perform computationally intensive simulations. The sampling
      method may affect the network structure and thus caution is necessary to
      generalize results based on samples. In this paper, we study four sampling
      strategies applied to a variety of real-life temporal networks. We quantify the
      biases generated by each sampling strategy on a number of relevant statistics
      such as link activity, temporal paths and epidemic spread. We find that some
      biases are common in a variety of networks and statistics, but one strategy,
      uniform sampling of nodes, shows improved performance in most scenarios. Given
      the particularities of temporal network data and the variety of network
      structures, we recommend that the choice of sampling methods be problem oriented
      to minimize the potential biases for the specific research questions on hand. Our
      results help researchers to better design network data collection protocols and
      to understand the limitations of sampled temporal network data.

PMID- 29347768
TI  - Zealotry effects on opinion dynamics in the adaptive voter model.
AB  - The adaptive voter model has been widely studied as a conceptual model for
      opinion formation processes on time-evolving social networks. Past studies on the
      effect of zealots, i.e., nodes aiming to spread their fixed opinion throughout
      the system, only considered the voter model on a static network. Here we extend
      the study of zealotry to the case of an adaptive network topology co-evolving
      with the state of the nodes and investigate opinion spreading induced by zealots
      depending on their initial density and connectedness. Numerical simulations
      reveal that below the fragmentation threshold a low density of zealots is
      sufficient to spread their opinion to the whole network. Beyond the transition
      point, zealots must exhibit an increased degree as compared to ordinary nodes for
      an efficient spreading of their opinion. We verify the numerical findings using a
      mean-field approximation of the model yielding a low-dimensional set of coupled
      ordinary differential equations. Our results imply that the spreading of the
      zealots' opinion in the adaptive voter model is strongly dependent on the link
      rewiring probability and the average degree of normal nodes in comparison with
      that of the zealots. In order to avoid a complete dominance of the zealots'
      opinion, there are two possible strategies for the remaining nodes: adjusting the
      probability of rewiring and/or the number of connections with other nodes,
      respectively.

PMID- 29347769
TI  - Physics behind the mechanical nucleosome positioning code.
AB  - The positions along DNA molecules of nucleosomes, the most abundant DNA-protein
      complexes in cells, are influenced by the sequence-dependent DNA mechanics and
      geometry. This leads to the "nucleosome positioning code", a preference of
      nucleosomes for certain sequence motives. Here we introduce a simplified model of
      the nucleosome where a coarse-grained DNA molecule is frozen into an idealized
      superhelical shape. We calculate the exact sequence preferences of our nucleosome
      model and find it to reproduce qualitatively all the main features known to
      influence nucleosome positions. Moreover, using well-controlled approximations to
      this model allows us to come to a detailed understanding of the physics behind
      the sequence preferences of nucleosomes.

PMID- 29347770
TI  - Viscosity of two-dimensional strongly coupled dusty plasma modified by a
      perpendicular magnetic field.
AB  - Transport properties of two-dimensional (2D) strongly coupled dusty plasmas have
      been investigated in detail, but never for viscosity with a strong perpendicular
      magnetic field; here, we examine this scenario using Langevin dynamics
      simulations of 2D liquids with a binary Yukawa interparticle interaction. The
      shear viscosity eta of 2D liquid dusty plasma is estimated from the simulation
      data using the Green-Kubo relation, which is the integration of the shear stress
      autocorrelation function. It is found that, when a perpendicular magnetic field
      is applied, the shear viscosity of 2D liquid dusty plasma is modified
      substantially. When the magnetic field is increased, its viscosity increases at
      low temperatures, while at high temperatures its viscosity diminishes. It is
      determined that these different variational trends of eta arise from the
      different behaviors of the kinetic and potential parts of the shear stress under
      external magnetic fields.

PMID- 29347771
TI  - Hierarchy measurement for modeling network dynamics under directed attacks.
AB  - A fundamental issue in the dynamics of complex systems is the resilience of the
      network in response to targeted attacks. This paper explores the local dynamics
      of the network attack process by investigating the order of removal of the nodes
      that have maximal degree, and shows that this dynamic network response can be
      predicted from the graph's initial connectivity. We demonstrate numerically that
      the maximal degree M(tau) of the network at time step tau decays exponentially
      with tau via a topology-dependent exponent. Moreover, the order in which sites
      are removed can be approximated by considering the network's "hierarchy" function
      h, which measures for each node V_{i} how many of its initial nearest neighbors
      have lower degree versus those that have a higher one. Finally, we show that the
      exponents we identified for the attack dynamics are related to the exponential
      behavior of spreading activation dynamics. The results suggest that the function
      h, which has both local and global properties, is a novel nodal measurement for
      network dynamics and structure.

PMID- 29347772
TI  - Energy nonequipartition in gas mixtures of inelastic rough hard spheres: The
      tracer limit.
AB  - The dynamical properties of a tracer or impurity particle immersed in a host gas
      of inelastic and rough hard spheres in the homogeneous cooling state is studied.
      Specifically, the breakdown of energy equipartition as characterized by the
      tracer/host ratios of translational and rotational temperatures is analyzed by
      exploring a wide spectrum of values of the control parameters of the system
      (masses, moments of inertia, sizes, and coefficients of restitution). Three
      complementary approaches are considered. On the theoretical side, the Boltzmann
      and Boltzmann-Lorentz equations (both assuming the molecular chaos ansatz) are
      solved by means of a multitemperature Maxwellian approximation for the velocity
      distribution functions. This allows us to obtain explicit analytical expressions
      for the temperature ratios. On the computational side, two different techniques
      are used. First, the kinetic equations are numerically solved by the direct
      simulation Monte Carlo (DSMC) method. Second, molecular dynamics simulations for
      dilute gases are performed. Comparison between theory and simulations shows a
      general good agreement. This means that (i) the impact of the molecular chaos
      ansatz on the temperature ratios is not significant (except at high
      inelasticities and/or big impurities) and (ii) the simple Maxwellian
      approximation yields quite reliable predictions.

PMID- 29347773
TI  - Hypothesis testing of scientific Monte Carlo calculations.
AB  - The steadily increasing size of scientific Monte Carlo simulations and the desire
      for robust, correct, and reproducible results necessitates rigorous testing
      procedures for scientific simulations in order to detect numerical problems and
      programming bugs. However, the testing paradigms developed for deterministic
      algorithms have proven to be ill suited for stochastic algorithms. In this paper
      we demonstrate explicitly how the technique of statistical hypothesis testing,
      which is in wide use in other fields of science, can be used to devise automatic
      and reliable tests for Monte Carlo methods, and we show that these tests are able
      to detect some of the common problems encountered in stochastic scientific
      simulations. We argue that hypothesis testing should become part of the standard
      testing toolkit for scientific simulations.

PMID- 29347774
TI  - Local and global avalanches in a two-dimensional sheared granular medium.
AB  - We present the experimental and numerical studies of a two-dimensional sheared
      amorphous material composed of bidisperse photoelastic disks. We analyze the
      statistics of avalanches during shear including the local and global fluctuations
      in energy and changes in particle positions and orientations. We find scale-free
      distributions for these global and local avalanches denoted by power laws whose
      cutoffs vary with interparticle friction and packing fraction. Different
      exponents are found for these power laws depending on the quantity from which
      variations are extracted. An asymmetry in time of the avalanche shapes is
      evidenced along with the fact that avalanches are mainly triggered by the shear
      bands. A simple relation independent of the intensity is found between the number
      of local avalanches and the global avalanches they form. We also compare these
      experimental and numerical results for both local and global fluctuations to
      predictions from mean-field and depinning theories.

PMID- 29347775
TI  - Mode locking in systems of globally coupled phase oscillators.
AB  - We investigate the dynamics of a Kuramoto-type system of globally coupled phase
      oscillators with equidistant natural frequencies and a coupling strength below
      the synchronization threshold. It turns out that in such cases one can observe a
      stable regime of sharp pulses in the mean field amplitude with a pulsation
      frequency given by spacing of the natural frequencies. This resembles a process
      known as mode locking in lasers and relies on the emergence of a phase relation
      induced by the nonlinear coupling. We discuss the role of the first and second
      harmonics in the phase-interaction function for the stability of the pulsations
      and present various bifurcating dynamical regimes such as periodically and
      chaotically modulated mode locking, transitions to phase turbulence, and
      intermittency. Moreover, we study the role of the system size and show that in
      certain cases one can observe type II supertransients, where the system reaches
      the globally stable mode-locking solution only after an exponentially long
      transient of phase turbulence.

PMID- 29347776
TI  - Entropy, specific heat, susceptibility, and Rushbrooke inequality in percolation.
AB  - We investigate percolation, a probabilistic model for continuous phase
      transition, on square and weighted planar stochastic lattices. In its thermal
      counterpart, entropy is minimally low where order parameter (OP) is maximally
      high and vice versa. In addition, specific heat, OP, and susceptibility exhibit
      power law when approaching the critical point and the corresponding critical
      exponents alpha,beta,gamma respectably obey the Rushbrooke inequality (RI)
      alpha+2beta+gamma>=2. Their analogs in percolation, however, remain elusive. We
      define entropy and specific heat and redefine susceptibility for percolation and
      show that they behave exactly in the same way as their thermal counterpart. We
      also show that RI holds for both the lattices albeit they belong to different
      universality classes.

PMID- 29347777
TI  - Power output for a nonlinear Brownian machine.
AB  - We propose a method that makes use of the nonlinear properties of some
      hypothetical microscopic solid material as the working substance for a
      microscopic machine. The protocols used are simple (step and elliptic) and allow
      us to obtain the work and heat exchanged between machine and reservoirs. We
      calculate the work for a nonlinear single-particle machine that can be treated
      perturbingly. We obtain the instantaneous work and heat for the machine
      undergoing cycles that mimic the Carnot and multireservoir protocols. The work
      calculations are then extended to high values of the nonlinear parameter yielding
      the quasistatic limit, which is verified numerically. The model we propose is
      fluctuation driven and we can study in detail its thermostatistics, namely, the
      work distribution both per cycle and instantaneous and the corresponding
      fluctuation relations.

PMID- 29347778
TI  - Forces in inhomogeneous open active-particle systems.
AB  - We study the force that noninteracting pointlike active particles apply to a
      symmetric inert object in the presence of a gradient of activity and particle
      sources and sinks. We consider two simple patterns of sources and sinks that are
      common in biological systems. We analytically solve a one-dimensional model
      designed to emulate higher-dimensional systems, and study a two-dimensional model
      by numerical simulations. We specify when the particle flux due to the creation
      and annihilation of particles can act to smooth the density profile that is
      induced by a gradient in the velocity of the active particles, and find the net
      resultant force due to both the gradient in activity and the particle flux. These
      results are compared qualitatively to observations of nuclear motion inside the
      oocyte, that is driven by a gradient in activity of actin-coated vesicles.

PMID- 29347779
TI  - Effective viscosity of a suspension of flagellar-beating microswimmers: Three
      dimensional modeling.
AB  - Micro-organisms usually can swim in their liquid environment by flagellar or
      ciliary beating. In this numerical work, we analyze the influence of flagellar
      beating on the orbits of a swimming cell in a shear flow. We also calculate the
      effect of the flagellar beating on the rheology of a dilute suspension of
      microswimmers. A three-dimensional model is proposed for Chlamydomonas
      Reinhardtii swimming with a breaststroke-like beating of two anterior flagella
      modeled by two counter-rotating fore beads. The active swimmer model reveals
      unusual angular orbits in a linear shear flow. Namely, the swimmer sustains
      orientations transiently across the flow. Such behavior is a result of the
      interplay between shear flow and the swimmer's periodic beating motion of
      flagella, which exert internal torques on the cell body. This peculiar behavior
      has some significant consequences on the rheological properties of the
      suspension. We calculate Einstein's viscosity of the suspension composed of such
      isolated modeled microswimmers (dilute case) in a shear flow. We use numerical
      simulations based on a Rotne-Prager-like approximation for hydrodynamic
      interaction between simplified flagella and the cell body. The results show an
      increased intrinsic viscosity for active swimmer suspensions in comparison to
      nonactive ones as well as a shear thinning behavior in accordance with previous
      experimental measurements [Phys. Rev. Lett. 104, 098102
      (2010)10.1103/PhysRevLett.104.098102].

PMID- 29347780
TI  - Stochastic thermodynamics for a periodically driven single-particle pump.
AB  - We present the stochastic thermodynamic analysis of a time-periodic single
      particle pump, including explicit results for flux, thermodynamic force, entropy
      production, work, heat, and efficiency. These results are valid far from
      equilibrium. The deviations from the linear (Onsager) regime are discussed.

PMID- 29347781
TI  - Flow properties and hydrodynamic interactions of rigid spherical microswimmers.
AB  - We analyze a minimal model for a rigid spherical microswimmer and explore the
      consequences of its extended surface on the interplay between its self-propulsion
      and flow properties. The model is the first order representation of
      microswimmers, such as bacteria and algae, with rigid bodies and flexible
      propelling appendages. The flow field of such a microswimmer at finite distances
      significantly differs from that of a point-force (Stokeslet) dipole. For a
      suspension of microswimmers, we derive the grand mobility matrix that connects
      the motion of an individual swimmer to the active and passive forces and torques
      acting on all the swimmers. Our investigation of the mobility tensors reveals
      that hydrodynamic interactions among rigid-bodied microswimmers differ
      considerably from those among the corresponding point-force dipoles. Our results
      are relevant for the study of collective behavior of hydrodynamically interacting
      microswimmers by means of Stokesian dynamics simulations at moderate
      concentrations.

PMID- 29347782
TI  - Stationary uphill currents in locally perturbed zero-range processes.
AB  - Uphill currents are observed when mass diffuses in the direction of the density
      gradient. We study this phenomenon in stationary conditions in the framework of
      locally perturbed one-dimensional zero range processes (ZRPs). We show that the
      onset of currents flowing from the reservoir with smaller density to the one with
      larger density can be caused by a local asymmetry in the hopping rates on a
      single site at the center of the lattice. For fixed injection rates at the
      boundaries, we prove that a suitable tuning of the asymmetry in the bulk may
      induce uphill diffusion at arbitrarily large, finite volumes. We also deduce
      heuristically the hydrodynamic behavior of the model and connect the local
      asymmetry characterizing the ZRP dynamics to a matching condition relevant for
      the macroscopic problem.

PMID- 29347783
TI  - Subjamming transition in binary sphere mixtures.
AB  - We study the influence of particle-size asymmetry on structural evolution of
      randomly jammed binary sphere mixtures with varying large-sphere and small-sphere
      composition. Simulations of jammed packings are used to assess the transition
      from large-sphere dominant to small-sphere dominant mixtures. For weakly
      asymmetric particle sizes, packing properties evolve smoothly, but not
      monotonically, with increasing small-sphere composition, f. Our simulations
      reveal that at high values of ratio alpha of large- to small-sphere radii
      (alpha>=alpha_{c}~5.75), evolution of structural properties, such as packing
      density, fraction of jammed spheres, and contact statistics with f, exhibit
      features that suggest a sharp transition, either through discontinuities in
      structural measures or their derivatives. We argue that this behavior is related
      to the singular, composition dependence of close-packing fraction predicted in
      infinite aspect ratio mixtures alpha->infinity by the Furnas model, but occurring
      for finite valued range of alpha above a critical value, alpha_{c}~5.75. The
      existence of a sharp transition from small- to large-f values for
      alpha>=alpha_{c} can be attributed to the existence of a subjamming transition of
      small spheres within the interstices of jammed large spheres along the line of
      compositions f_{sub}(alpha). We argue that the critical value of finite-size
      asymmetry alpha_{c}?5.75 is consistent with the geometric criterion for the
      transmission of small-sphere contacts between neighboring tetrahedrally close
      packed interstices of large spheres, facilitating a cooperative subjamming
      transition of small spheres confined within the disjoint volumes.

PMID- 29347784
TI  - Parametric pulse amplification by acoustic quasimodes in electron-positron
      plasma.
AB  - In a recent paper, M. R. Edwards, N. J. Fisch, and J. M. Mikhailova [Phys. Rev.
      Lett. 116, 015004 (2016)PRLTAO0031-900710.1103/PhysRevLett.116.015004] reported
      that in electron-positron plasma stimulated Brillouin scattering is drastically
      enhanced, while stimulated Raman scattering is completely absent. However, when
      theory was compared to particle-in-cell (PIC) simulations, a discrepancy by at
      least a factor four appeared. Authors correctly argued that the disparity might
      be due to the fluid approximation of the low-frequency mode. They noted that a
      more precise analytic description of the acoustic resonance requires a kinetic
      approach, which was beyond the scope of the mentioned paper. Here we deliver the
      so-far-missing kinetic calculation. It shows quite good agreement with the PIC
      simulations presented in the above-mentioned paper by Edwards et al. The
      principal result of enhancement of Brillouin scattering and absence of Raman
      scattering remains valid. The Brillouin enhancement factors depend on electron
      temperature and background particle density. These dependencies as well as the
      transition to the well-known behavior of electron-ion plasma are discussed. It is
      also shown that pulse amplification in electron-positron plasma crosses over to
      the strong-coupling regime when the pump amplitude becomes large. Then, the fluid
      approximation becomes acceptable again.

PMID- 29347785
TI  - Discontinuous fluidization transition in time-correlated assemblies of actively
      deforming particles.
AB  - Tracking experiments in dense biological tissues reveal a diversity of sources
      for local energy injection at the cell scale. The effect of cell motility has
      been largely studied, but much less is known about the effect of the observed
      volume fluctuations of individual cells. We consider a microscopic model of
      "actively deforming" particles where local fluctuations of the particle size
      constitute a unique source of motion. We demonstrate that collective motion can
      emerge under the sole influence of such active volume fluctuations. We interpret
      the onset of diffusive motion as a nonequilibrium first-order phase transition,
      which arises at a well-defined amplitude of self-deformation. This behavior
      contrasts with the glassy dynamics produced by self-propulsion, but resembles the
      mechanical response of soft solids under mechanical deformation. It thus
      constitutes an example of an active yielding transition.

PMID- 29347786
TI  - Dynamics of a magnetic active Brownian particle under a uniform magnetic field.
AB  - The dynamics of a magnetic active Brownian particle undergoing three-dimensional
      Brownian motion, both translation and rotation, under the influence of a uniform
      magnetic field is investigated. The particle self-propels at a constant speed
      along its magnetic dipole moment, which reorients due to the interplay between
      Brownian and magnetic torques, quantified by the Langevin parameter alpha. In
      this work, the time-dependent active diffusivity and the crossover time
      (tau^{cross})-from ballistic to diffusive regimes-are calculated through the time
      dependent correlation function of the fluctuations of the propulsion direction.
      The results reveal that, for any value of alpha, the particle undergoes a
      directional (or ballistic) propulsive motion at very short times (t?tau^{cross}).
      In this regime, the correlation function decreases linearly with time, and the
      active diffusivity increases with it. It the opposite time limit (t?tau^{cross}),
      the particle moves in a purely diffusive regime with a correlation function that
      decays asymptotically to zero and an active diffusivity that reaches a constant
      value equal to the long-time active diffusivity of the particle. As expected in
      the absence of a magnetic field (alpha=0), the crossover time is equal to the
      characteristic time scale for rotational diffusion, tau_{rot}. In the presence of
      a magnetic field (alpha>0), the correlation function, the active diffusivity, and
      the crossover time decrease with increasing alpha. The magnetic field regulates
      the regimes of propulsion of the particle. Here, the field reduces the period of
      time at which the active particle undergoes a directional motion. Consequently,
      the active particle rapidly reaches a diffusive regime at tau^{cross}?tau_{rot}.
      In the limit of weak fields (alpha?1), the crossover time decreases quadratically
      with alpha, while in the limit of strong fields (alpha?1) it decays
      asymptotically as alpha^{-1}. The results are in excellent agreement with those
      obtained by Brownian dynamics simulations.

PMID- 29347787
TI  - Direct determination approach for the multifractal detrending moving average
      analysis.
AB  - In the canonical framework, we propose an alternative approach for the
      multifractal analysis based on the detrending moving average method (MF-DMA). We
      define a canonical measure such that the multifractal mass exponent tau(q) is
      related to the partition function and the multifractal spectrum f(alpha) can be
      directly determined. The performances of the direct determination approach and
      the traditional approach of the MF-DMA are compared based on three synthetic
      multifractal and monofractal measures generated from the one-dimensional p-model,
      the two-dimensional p-model, and the fractional Brownian motions. We find that
      both approaches have comparable performances to unveil the fractal and
      multifractal nature. In other words, without loss of accuracy, the multifractal
      spectrum f(alpha) can be directly determined using the new approach with less
      computation cost. We also apply the new MF-DMA approach to the volatility time
      series of stock prices and confirm the presence of multifractality.

PMID- 29347788
TI  - Particle transport across a channel via an oscillating potential.
AB  - Membrane protein transporters alternate their substrate-binding sites between the
      extracellular and cytosolic side of the membrane according to the alternating
      access mechanism. Inspired by this intriguing mechanism devised by nature, we
      study particle transport through a channel coupled with an energy well that
      oscillates its position between the two entrances of the channel. We optimize
      particle transport across the channel by adjusting the oscillation frequency. At
      the optimal oscillation frequency, the translocation rate through the channel is
      a hundred times higher with respect to free diffusion across the channel. Our
      findings reveal the effect of time-dependent potentials on particle transport
      across a channel and will be relevant for membrane transport and microfluidics
      application.

PMID- 29347789
TI  - Optimal paths on the road network as directed polymers.
AB  - We analyze the statistics of the shortest and fastest paths on the road network
      between randomly sampled end points. We find that, to a good approximation, the
      optimal paths can be described as directed polymers in a disordered medium, which
      belong to the Kardar-Parisi-Zhang universality class of interface roughening.
      Comparing the scaling behavior of our data with simulations of directed polymers
      and previous theoretical results, we are able to point out the few
      characteristics of the road network that are relevant to the large-scale
      statistics of optimal paths. Indeed, we show that the local structure is akin to
      a disordered environment with a power-law distribution which become less
      important at large scales where long-ranged correlations in the network control
      the scaling behavior of the optimal paths.

PMID- 29347790
TI  - Finite connected components in infinite directed and multiplex networks with
      arbitrary degree distributions.
AB  - This work presents exact expressions for size distributions of weak and
      multilayer connected components in two generalizations of the configuration
      model: networks with directed edges and multiplex networks with an arbitrary
      number of layers. The expressions are computable in a polynomial time and, under
      some restrictions, are tractable from the asymptotic theory point of view. If
      first partial moments of the degree distribution are finite, the size
      distribution for two-layer connected components in multiplex networks exhibits an
      exponent -3/2 in the critical regime, whereas the size distribution of weakly
      connected components in directed networks exhibits two critical exponents -1/2
      and -3/2.

PMID- 29347791
TI  - Beyond the faster-is-slower effect.
AB  - The "faster-is-slower" effect arises when crowded people push each other to
      escape through an exit during an emergency situation. As individuals push harder,
      a statistical slowing down in the evacuation time can be achieved. The slowing
      down is caused by the presence of small groups of pedestrians (say, a small human
      cluster) that temporarily block the way out when trying to leave the room. The
      pressure on the pedestrians belonging to this blocking cluster increases for
      increasing anxiety levels and/or a larger number of individuals trying to leave
      the room through the same door. Our investigation shows, however, that very high
      pressures alter the dynamics in the blocking cluster and, thus, change the
      statistics of the time delays along the escaping process. A reduction in the long
      lasting delays can be acknowledged, while the overall evacuation performance
      improves. We present results on this phenomenon taking place beyond the faster-is
      slower regime.

PMID- 29347792
TI  - Resonances in a periodically driven bosonic system.
AB  - Periodically driven systems are a common topic in modern physics. In optical
      lattices specifically, driving is at the origin of many interesting phenomena.
      However, energy is not conserved in driven systems, and under periodic driving,
      heating of a system is a real concern. In an effort to better understand this
      phenomenon, the heating of single-band systems has been studied, with a focus on
      disorder- and interaction-induced effects, such as many-body localization.
      Nevertheless, driven systems occur in a much wider context than this, leaving
      room for further research. Here, we fill this gap by studying a noninteracting
      model, characterized by discrete, periodically spaced energy levels that are
      unbounded from above. We couple these energy levels resonantly through a periodic
      drive, and discuss the heating dynamics of this system as a function of the
      driving protocol. In this way, we show that a combination of stimulated emission
      and absorption causes the presence of resonant stable states. This will serve to
      elucidate the conditions under which resonant driving causes heating in quantum
      systems.

PMID- 29347793
TI  - Instabilities of an annulus flow between rotating cylinders in a helical magnetic
      field.
AB  - The stabilities of an annulus flow between the rotating inner and outer cylinders
      with an external helical magnetic field are studied by using the quasistatic
      approximation. It is shown numerically that for the spiral base flow with a zero
      axial pressure gradient, the helical magnetic field yields a helical traveling
      wave at a critical Reynolds number. This wave mode is revealed to be the most
      unstable mode by linear stability analysis. At higher Reynolds numbers, the first
      wave mode is superposed by a second antisymmetric helical wave mode, which
      travels with a higher phase velocity than the first mode. When the Reynolds
      number is increased further, the flow becomes turbulent, but the key features of
      the flow structure are still dominated by the first and the second wave modes.
      Furthermore, when a finite axial pressure gradient is applied to guarantee a zero
      axial flow rate, the annulus flow is found to be more unstable than the case with
      zero axial pressure gradient.

PMID- 29347794
TI  - Publisher's Note: Discovering phases, phase transitions, and crossovers through
      unsupervised machine learning: A critical examination [Phys. Rev. E 95, 062122
      (2017)].
AB  - This corrects the article DOI: 10.1103/PhysRevE.95.062122.

PMID- 29347795
TI  - Kibble-Zurek scaling of the irreversible entropy production.
AB  - If a system is driven at finite rate through a phase transition by varying an
      intensive parameter, the order parameter shatters into finite domains. The Kibble
      Zurek mechanism predicts the typical size of these domains, which are governed
      only by the rate of driving and the spatial and dynamical critical exponents. We
      show that also the irreversible entropy production fulfills a universal behavior,
      which however is determined by an additional critical exponent corresponding to
      the intensive control parameter. Our universal prediction is numerically tested
      in two systems exhibiting noise-induced phase transitions.

PMID- 29347796
TI  - Headward growth and branching in subterranean channels.
AB  - We investigate the erosive growth of channels in a thin subsurface sedimentary
      layer driven by hydrodynamic drag toward understanding subterranean networks and
      their relation to river networks charged by ground water. Building on a model
      based on experimental observations of fluid-driven evolution of bed porosity, we
      focus on the characteristics of the channel growth and their bifurcations in a
      horizontal rectangular domain subject to various fluid source and sink
      distributions. We find that the erosion front between low- and high-porosity
      regions becomes unstable, giving rise to branched channel networks, depending on
      the spatial fluctuations of the fluid flow near the front and the degree to which
      the flow is above the erodibility threshold of the medium. Focusing on the growth
      of a network starting from a single channel, and by identifying the channel heads
      and their branch points, we find that the number of branches increases
      sublinearly and is affected by the source distribution. The mean angles between
      branches are found to be systematically lower than river networks in humid
      climates and depend on the domain geometry.

PMID- 29347797
TI  - Relaxation, thermalization, and Markovian dynamics of two spins coupled to a spin
      bath.
AB  - It is shown that by fitting a Markovian quantum master equation to the numerical
      solution of the time-dependent Schrodinger equation of a system of two spin-1/2
      particles interacting with a bath of up to 34 spin-1/2 particles, the former can
      describe the dynamics of the two-spin system rather well. The fitting procedure
      that yields this Markovian quantum master equation accounts for all non-Markovian
      effects in as much the general structure of this equation allows and yields a
      description that is incompatible with the Lindblad equation.

PMID- 29347798
TI  - Dispersion of the intrinsic neuronal periods affects the relationship of the
      entrainment range to the coupling strength in the suprachiasmatic nucleus.
AB  - Living beings on the Earth are subjected to and entrained (synchronized) to the
      natural 24-h light-dark cycle. Interestingly, they can also be entrained to an
      external artificial cycle of non-24-h periods. The range of these periods is
      called the entrainment range and it differs among species. In mammals, the
      entrainment range is regulated by a main clock located in the suprachiasmatic
      nucleus (SCN) which is composed of 10 000 neurons in the brain. Previous works
      have found that the entrainment range depends on the cellular coupling strength
      in the SCN. In particular, the entrainment range decreases with the increase of
      the cellular coupling strength, provided that all the neuronal oscillators are
      identical. However, the SCN neurons differ in the intrinsic periods that follow a
      normal distribution in a range from 22 to 28 h. In the present study, taking the
      dispersion of the intrinsic neuronal periods into account, we examined the
      relationship between the entrainment range and the coupling strength. Results
      from numerical simulations and theoretical analyses both show that the
      relationship is altered to be paraboliclike if the intrinsic neuronal periods are
      nonidentical, and the maximal entrainment range is obtained with a suitable
      coupling strength. Our results shed light on the role of the cellular coupling in
      the entrainment ability of the SCN network.

PMID- 29347799
TI  - Confinement effects in premelting dynamics.
AB  - We examine the effects of confinement on the dynamics of premelted films driven
      by thermomolecular pressure gradients. Our approach is to modify a well-studied
      setting in which the thermomolecular pressure gradient is driven by a temperature
      gradient parallel to an interfacially premelted elastic wall. The modification
      treats the increase in viscosity associated with the thinning of films, studied
      in a wide variety of materials, using a power law and we examine the consequent
      evolution of the confining elastic wall. We treat (1) a range of interactions
      that are known to underlie interfacial premelting and (2) a constant temperature
      gradient wherein the thermomolecular pressure gradient is a constant. The
      difference between the cases with and without the proximity effect arises in the
      volume flux of premelted liquid. The proximity effect increases the viscosity as
      the film thickness decreases thereby requiring the thermomolecular pressure
      driven flux to be accommodated at higher temperatures where the premelted film
      thickness is the largest. Implications for experiment and observations of frost
      heave are discussed.

PMID- 29347800
TI  - Roughness-enhanced transport in a tilted ratchet driven by Levy noise.
AB  - The enhanced transport of particles by roughness in a tilted rough ratchet
      potential subject to a Levy noise is investigated in this paper. Due to the
      roughness, the transport process exhibits quite different properties compared to
      the smooth case. We find that the roughness on the potential wall functions like
      a ladder to provide the convenience for particles to climb up but hinder them to
      slide down. The mean first passage time from one well to its right adjacent well
      and the mean velocity are, respectively, calculated versus the roughness, the
      external force, and the Levy stability index. Our results show that the roughness
      is able to induce an enhancement on the mean velocity of particles and accelerate
      the barrier crossing process. The general conditions require a small external
      force and a small Levy stability index. We find that with increasing external
      forces, the enhancement areas of roughness and Levy stability index both shrink.
      However, for the Levy stability index within the enhancement area, its increase
      will enlarge the enhancement area of roughness. On the contrary, under the same
      conditions we observe that for a Gaussian noise the roughness always reduces the
      corresponding mean velocity which is very different from the case of Levy noise.

PMID- 29347801
TI  - Erratum: Aging Wiener-Khinchin theorem and critical exponents of 1/f^{beta} noise
      [Phys. Rev. E 94, 052130 (2016)].
AB  - This corrects the article DOI: 10.1103/PhysRevE.94.052130.

PMID- 29347802
TI  - Entropy production and volume contraction in thermostated Hamiltonian dynamics.
AB  - Patra et al. [Int. J. Bifurcat. Chaos 26, 1650089 (2016)IJBEE40218
      127410.1142/S0218127416500899] recently showed that the time-averaged rates of
      entropy production and phase-space volume contraction are equal for several
      different molecular dynamics methods used to simulate nonequilibrium steady
      states in Hamiltonian systems with thermostated temperature gradients. This
      equality is a plausible statistical analog of the second law of thermodynamics.
      Here we show that those two rates are identically equal in a wide class of
      methods in which the thermostat variables z are determined by ordinary
      differential equations of motion (i.e., methods of the Nose-Hoover or integral
      feedback control type). This class of methods is defined by three relatively
      innocuous restrictions which are typically satisfied in methods of this type.

PMID- 29347803
TI  - Experimental determination of phase transitions by means of configurational
      entropies in finite Yukawa balls.
AB  - The phase transition of finite Yukawa balls (ordered systems of microspheres in a
      gaseous plasma environment) with less than 100 particles is studied
      experimentally by means of configurational entropies. We have developed
      cylindrical two- and three-particle-correlation functions to measure these
      entropies for multiple cluster sizes over a wide temperature range. The cluster
      temperature is finely tuned using a stochastic laser heating setup. It is shown
      that the correlation functions give a detailed insight into the structural
      properties of the cluster. The derived configurational entropies give a clear
      indication of the transition temperature from a solid-like to a fluid-like state.
      Comparing the transition temperatures of different sized clusters it is found
      that the transition temperature increases with cluster size in general agreement
      with theoretical predictions.

PMID- 29347804
TI  - Active nematic gels as active relaxing solids.
AB  - I propose a continuum theory for active nematic gels, defined as fluids or
      suspensions of orientable rodlike objects endowed with active dynamics, that is
      based on symmetry arguments and compatibility with thermodynamics. The starting
      point is our recent theory that models (passive) nematic liquid crystals as
      relaxing nematic elastomers. The interplay between viscoelastic response and
      active dynamics of the microscopic constituents is naturally taken into account.
      By contrast with standard theories, activity is not introduced as an additional
      term of the stress tensor, but it is added as an external remodeling force that
      competes with the passive relaxation dynamics and drags the system out of
      equilibrium. In a simple one-dimensional channel geometry, we show that the
      interaction between nonuniform nematic order and activity results in either a
      spontaneous flow of particles or a self-organization into subchannels flowing in
      opposite directions.

PMID- 29347805
TI  - Spectral signatures of activity-dependent neural feedback in the corticothalamic
      system.
AB  - The modulation of neural quantities by presynaptic and postsynaptic activities
      via local feedback processes is investigated by incorporating nonlinear phenomena
      such as relative refractory period, synaptic enhancement, synaptic depression,
      and habituation. This is done by introducing susceptibilities, which quantify the
      response in either firing threshold or synaptic strength to unit change in either
      presynaptic or postsynaptic activity. Effects on the power spectra are then
      analyzed for a realistic corticothalamic model to determine the spectral
      signatures of various nonlinear processes and to what extent these are distinct.
      Depending on the feedback processes, there can be enhancements or reductions in
      low-frequency and/or alpha power, splitting of the alpha resonance, and/or
      appearance of new resonances at high frequencies. These features in the power
      spectra allow processes to be fully distinguished where they are unique, or
      partly distinguished if they are common to only a subset of feedbacks, and can
      potentially be used to constrain the types, strengths, and dynamics of feedbacks
      present.

PMID- 29347806
TI  - Synchrony-induced modes of oscillation of a neural field model.
AB  - We investigate the modes of oscillation of heterogeneous ring networks of
      quadratic integrate-and-fire (QIF) neurons with nonlocal, space-dependent
      coupling. Perturbations of the equilibrium state with a particular wave number
      produce transient standing waves with a specific temporal frequency, analogously
      to those in a tense string. In the neuronal network, the equilibrium corresponds
      to a spatially homogeneous, asynchronous state. Perturbations of this state
      excite the network's oscillatory modes, which reflect the interplay of episodes
      of synchronous spiking with the excitatory-inhibitory spatial interactions. In
      the thermodynamic limit, an exact low-dimensional neural field model describing
      the macroscopic dynamics of the network is derived. This allows us to obtain
      formulas for the Turing eigenvalues of the spatially homogeneous state and hence
      to obtain its stability boundary. We find that the frequency of each Turing mode
      depends on the corresponding Fourier coefficient of the synaptic pattern of
      connectivity. The decay rate instead is identical for all oscillation modes as a
      consequence of the heterogeneity-induced desynchronization of the neurons.
      Finally, we numerically compute the spectrum of spatially inhomogeneous solutions
      branching from the Turing bifurcation, showing that similar oscillatory modes
      operate in neural bump states and are maintained away from onset.

PMID- 29347807
TI  - Role of matrix behavior in compressive fracture of bovine cortical bone.
AB  - In compressive fracture of dry plexiform bone, we examine the individual roles of
      overall mean porosity, the connectivity of the porosity network, and the elastic
      as well as the failure properties of the nonporous matrix, using a random spring
      network model (RSNM). Porosity network structure is shown to reduce the
      compressive strength by up to 30%. However, the load-bearing capacity increases
      with an increase in either of the matrix properties-the elastic modulus or the
      failure strain threshold. To validate the porosity-based RSNM model with
      available experimental data, bone-specific failure strain thresholds for the
      ideal matrix of similar elastic properties were estimated to be within 60% of
      each other. Further, we observe the avalanche size exponents to be independent of
      the bone-dependent parameters as well as the structure of the porosity network.

PMID- 29347808
TI  - Thermodynamic theory of dislocation-enabled plasticity.
AB  - The thermodynamic theory of dislocation-enabled plasticity is based on two
      unconventional hypotheses. The first of these is that a system of dislocations,
      driven by external forces and irreversibly exchanging heat with its environment,
      must be characterized by a thermodynamically defined effective temperature that
      is not the same as the ordinary temperature. The second hypothesis is that the
      overwhelmingly dominant mechanism controlling plastic deformation is thermally
      activated depinning of entangled pairs of dislocations. This paper consists of a
      systematic reformulation of this theory followed by examples of its use in
      analyses of experimentally observed phenomena including strain hardening, grain
      size (Hall-Petch) effects, yielding transitions, and adiabatic shear banding.

PMID- 29347809
TI  - Transient subdiffusion from an Ising environment.
AB  - We introduce a model in which a particle performs a continuous-time random walk
      (CTRW) coupled to an environment with Ising dynamics. The particle shows locally
      varying diffusivity determined by the geometrical properties of the underlying
      Ising environment, that is, the diffusivity depends on the size of the connected
      area of spins pointing in the same direction. The model shows anomalous diffusion
      when the Ising environment is at critical temperature. We show that any finite
      scale introduced by a temperature different from the critical one, or a finite
      size of the environment, cause subdiffusion only during a transient time. The
      characteristic time, at which the system returns to normal diffusion after the
      subdiffusive plateau depends on the limiting scale and on how close the
      temperature is to criticality. The system also displays apparent ergodicity
      breaking at intermediate time, while ergodicity breaking at longer time occurs
      only under the idealized infinite environment at the critical temperature.

PMID- 29347810
TI  - Plasma q-plate for generation and manipulation of intense optical vortices.
AB  - An optical vortex is a light wave with a twisting wavefront around its
      propagation axis and null intensity in the beam center. Its unique spatial
      structure of field lends itself to a broad range of applications, including
      optical communication, quantum information, superresolution microscopy, and
      multidimensional manipulation of particles. However, accessible intensity of
      optical vortices have been limited to material ionization threshold. This
      limitation might be removed by using the plasma medium. Here we propose the
      design of suitably magnetized plasmas which, functioning as a q-plate, leads to a
      direct conversion from a high-intensity Gaussian beam into a twisted beam. A
      circularly polarized laser beam in the plasma accumulates an azimuthal-angle
      dependent phase shift and hence forms a twisting wavefront. Our three-dimensional
      particle-in-cell simulations demonstrate extremely high-power conversion
      efficiency. The plasma q-plate can work in a large range of frequencies spanning
      from terahertz to the optical domain.

PMID- 29347811
TI  - Orientation-shape coupling between liquid crystal and membrane through the
      anchoring effect.
AB  - We perform a series of Monte Carlo simulations on an interface between a liquid
      crystal (LC) material in isotropic phase in its bulk and a surfactant membrane.
      These two objects are simulated using coarse-grained molecular models. We
      estimate physical properties of the membrane such as the interfacial tension and
      the bending rigidity, focusing on the anchoring effects of the membrane on the
      LC. According to our simulation results, when the strength of the homeotropic
      anchoring denoted by the anchoring parameter xi is increased, the interfacial
      tension decreases and the bending rigidity first increases in xi<xi_{m}, and it
      then decreases in xi_{m}<xi. We explain these results by constructing a continuum
      field model based on the two order parameters: directional order of LC and the
      membrane shape. These order parameters are mutually interacting through the
      anchoring effect, the fluctuation coupling between the LC and the membrane, and
      the effect of the nematic layer.

PMID- 29347812
TI  - Reevaluation of the impact of methicillin-resistance on outcomes in patients with
      Staphylococcus aureus bacteremia and endocarditis.
AB  - Background/Aims: Methicillin-resistant Staphylococcus aureus (MRSA) is highly
      prevalent in hospitals, and has recently emerged in the community. The impact of
      methicillin-resistance on mortality and medical costs for patients with S. aureus
      bacteremia (SAB) requires reevaluation. Methods: We searched studies with SAB or
      endocarditis using electronic databases including Ovid-Medline, Embase-Medline,
      and Cochrane Library, as well as five local databases for published studies
      during the period January 2000 to September 2011. Results: A total of 2,841
      studies were identified, 62 of which involved 17,563 adult subjects and were
      selected as eligible. A significant increase in overall mortality associated with
      MRSA, compared to that with methicillin-susceptible S. aureus (MSSA), was
      evidenced by an odds ratio (OR) of 1.95 (95% confidence interval [CI], 1.73 to
      2.21; p < 0.01). In 13 endocarditis studies, MRSA increased the risk of
      mortality, with an OR of 2.65 (95% CI, 1.46 to 4.80). When three studies, which
      compared mortality rates between CA-MRSA and CA-MSSA, were combined, the risk of
      methicillin-resistance increased 3.23-fold compared to MSSA (95% CI, 1.25 to
      8.34). The length of hospital stay in the MRSA group was 10 days longer than that
      in the MSSA group (95% CI, 3.36 to 16.70). Of six studies that reported medical
      costs, two were included in the analysis, which estimated medical costs to be
      $9,954.58 (95% CI, 8,951.99 to 10,957.17). Conclusions: MRSA is still associated
      with increased mortality, longer hospital stays and medical costs, compared with
      MSSA in SAB in studies published since the year 2000.

PMID- 29347813
TI  - The usefulness of fecal calprotectin in assessing inflammatory bowel disease
      activity.
AB  - Background/Aims: Fecal calprotectin (FC) is known to correlate with disease
      activity and can be used as a predictor for relapse or treatment response in
      inflammatory bowel disease (IBD). We evaluated the usefulness of FC as a
      biomarker for disease activity in patients with IBD using both enzyme-linked
      immunosorbent assay (ELISA) and a quantitative point-of-care test (QPOCT).
      Methods: Fecal samples and medical records were collected from consecutive
      patients with IBD. FC levels were measured by both ELISA and QPOCT and patient
      medical records were reviewed for clinical, laboratory, and endoscopic data.
      Results: Ninety-three patients with IBD were enrolled, 55 with ulcerative colitis
      (UC) and 38 with Crohn's disease (CD). The mean FC-ELISA levels were 906.3 +/-
      1,484.9 MUg/g in UC and 1,054.1 +/- 1,252.5 MUg/g in CD. There was a strong
      correlation between FC-ELISA level and clinical activity indices (p < 0.05). FC
      ELISA level was significantly lower in patients with mucosal healing (MH)
      compared to those without MH in UC (85.5 +/- 55.6 MUg/g vs. 1,503.7 +/- 2,129.9
      MUg/g, p = 0.005). The results from the QPOCT corresponded well to those from
      ELISA. A cutoff value of 201.3 MUg/g for FC-ELISA and 150.5 MUg/g for FC-QPOCT
      predicted endoscopic inflammation (Mayo endoscopic subscore >= 1) in UC with a
      sensitivity of 81.8% and 85.8%, respectively, and a specificity of 100% for both.
      Conclusions: FC was strongly associated with disease activity indices, serologic
      markers, and endoscopic activity in patients with IBD. QPOCT can be used more
      conveniently than ELISA to assess FC in clinical practice.

PMID- 29347814
TI  - [Customization of hormonal contraception].
AB  - In the last few years new oral contraceptives have been marketed showing a better
      safety profile for women. They are the result of important changes made to the
      old compounds. As far as the estrogenic component, with the aim of decreasing
      side effects, the dose of ethinyl estradiol has been reduced and synthetic
      estrogens have been replaced by natural estradiol, further improving the safety
      profile. Also the progestin component in the last years has been changed in terms
      of dose, endocrine and metabolic characteristics. Levonorgestrel is an androgenic
      progestin, but now there is the possibility of choosing progestins without
      androgenic effect (gestodene and desogestrel) or progestins with antiandrogenic
      effect (cyproterone acetate, dienogest, drospirenone, chlormadinone acetate),
      very useful in patients with hyperandrogenism. Some of these progestins, like
      Drospirenone, represented the real held contributing, because of its
      antimineralcorticoid action, to reduce an important side effect like fluid
      retention; moreover there is the possibility to choose products with high
      progestogen effect on endometrium (dienogest, nomegestrole acetate), resulting
      very effective in women with abnormal uterine bleedings. Also the regimens of
      administration have been changed, by shortening or eliminating the tablet-free
      period; in this way the women may avoid premenstrual symptoms. The oral is not
      the only route of administration, but today there are alternative routes like
      transdermal, transvaginal, intrauterine and subcutaneous, reducing gastro
      intestinal interferences and possible mistakes in pill intake.

PMID- 29347815
TI  - Control over Electron-Phonon Interaction by Dirac Plasmon Engineering in the
      Bi2Se3 Topological Insulator.
AB  - Understanding the mutual interaction between electronic excitations and lattice
      vibrations is key for understanding electronic transport and optoelectronic
      phenomena. Dynamic manipulation of such interaction is elusive because it
      requires varying the material composition on the atomic level. In turn, recent
      studies on topological insulators (TIs) have revealed the coexistence of a strong
      phonon resonance and topologically protected Dirac plasmon, both in the terahertz
      (THz) frequency range. Here, using these intrinsic characteristics of TIs, we
      demonstrate a new methodology for controlling electron-phonon interaction by
      lithographically engineered Dirac surface plasmons in the Bi2Se3 TI. Through a
      series of time-domain and time-resolved ultrafast THz measurements, we show that,
      when the Dirac plasmon energy is less than the TI phonon energy, the electron
      phonon coupling is trivial, exhibiting phonon broadening associated with Landau
      damping. In contrast, when the Dirac plasmon energy exceeds that of the phonon
      resonance, we observe suppressed electron-phonon interaction leading to
      unexpected phonon stiffening. Time-dependent analysis of the Dirac plasmon
      behavior, phonon broadening, and phonon stiffening reveals a transition between
      the distinct dynamics corresponding to the two regimes as the Dirac plasmon
      resonance moves across the TI phonon resonance, which demonstrates the capability
      of Dirac plasmon control. Our results suggest that the engineering of Dirac
      plasmons provides a new alternative for controlling the dynamic interaction
      between Dirac carriers and phonons.

PMID- 29347816
TI  - Pb-Activated Amine-Assisted Photocatalytic Hydrogen Evolution Reaction on Organic
      Inorganic Perovskites.
AB  - We report here the reaction mechanism for explicit aqueous solvent quantum
      mechanics (QM) studies determining the energetics and reaction barriers for the
      photocatalytic hydrogen evolution reaction (HER) on CH3NH3PbI3 surface. We find
      that both the lead (Pb) atoms and the surface organic molecules play essential
      roles, leading to a two-step Pb-activated amine-assisted (PbAAA) reaction
      mechanism involving an intermediate lead hydride state. Both H of H2 product are
      extracted from surface organic molecules, while two protons from the solution
      migrate along water chains via the Grotthuss mechanism to replace the H in
      organic molecule. We obtain a reaction barrier of 1.08 eV for photochemical
      generation of H2 on CH3NH3PbI3 compared to 2.61 eV for the dark reaction. We
      expect this HER mechanism can also apply to the other organic perovskites, but
      the energy barriers and reaction rates may depend on the basicity of electrolyte
      and intrinsic structures of perovskites.

PMID- 29347817
TI  - Biochemical Basis of APOBEC3 Deoxycytidine Deaminase Activity on Diverse DNA
      Substrates.
AB  - The Apolipoprotein B mRNA editing complex (APOBEC) family of enzymes contains
      single-stranded polynucleotide cytidine deaminases. These enzymes catalyze the
      deamination of cytidine in RNA or single-stranded DNA, which forms uracil. From
      this 11 member enzyme family in humans, the deamination of single-stranded DNA by
      the seven APOBEC3 family members is considered here. The APOBEC3 family has many
      roles, such as restricting endogenous and exogenous retrovirus replication and
      retrotransposon insertion events and reducing DNA-induced inflammation. Similar
      to other APOBEC family members, the APOBEC3 enzymes are a double-edged sword that
      can catalyze deamination of cytosine in genomic DNA, which results in potential
      genomic instability due to the many mutagenic fates of uracil in DNA. Here, we
      discuss how these enzymes find their single-stranded DNA substrate in different
      biological contexts such as during human immunodeficiency virus (HIV) proviral
      DNA synthesis, retrotransposition of the LINE-1 element, and the "off-target"
      genomic DNA substrate. The enzymes must be able to efficiently deaminate
      transiently available single-stranded DNA during reverse transcription,
      replication, or transcription. Specific biochemical characteristics promote
      deamination in each situation to increase enzyme efficiency through processivity,
      rapid enzyme cycling between substrates, or oligomerization state. The use of
      biochemical data to clarify biological functions and alignment with cellular data
      is discussed. Models to bridge knowledge from biochemical, structural, and single
      molecule experiments are presented.

PMID- 29347818
TI  - Far-Red Fluorescent Probe for Imaging of Vicinal Dithiol-Containing Proteins in
      Living Cells Based on a pKa Shift Mechanism.
AB  - Vicinal dithiol-containing proteins (VDPs) play fundamental roles in
      intracellular redox homeostasis and are responsible for many diseases. In this
      work, we report a far-red fluorescence turn-on probe MCAs for VDPs exploiting the
      pKa shift of the imine functionality of the probe. MCAs is composed of a
      merocyanine Schiff base as the fluorescent reporter and a cyclic 1,3,2
      dithiarsenolane as the specific ligand for VDPs. The imine pKa of MCAs is 4.8,
      and it exists predominantly in the Schiff base (SB) form at physiological pH. Due
      to the absence of a resonating positive charge, it absorbs at a relatively short
      wavelength and is essentially nonfluorescent. Upon selective binding to reduced
      bovine serum albumin (rBSA, selected as the model protein), MCAs was brought from
      aqueous media to the binding pockets of the protein, causing a large increase in
      pKa value of MCAs (pKa = 7.1). As a result, an increase in the protonated Schiff
      base (PSB) form of MCAs was observed at the physiological pH conditions, which in
      turn leads to a bathochromically shifted chromophore (lambdaabs = 634 nm) and a
      significant increase in fluorescence intensity (lambdaem = 657 nm)
      simultaneously. Furthermore, molecular dynamics simulations indicate that the
      salt bridges formed between the iminium in MCAs and the residues D72 and D517 in
      rBSA resist the dissociation of proton from the probe, thus inducing an increase
      of the pKa value. The proposed probe shows excellent sensitivity and specificity
      toward VDPs over other proteins and biologically relevant species and has been
      successfully applied for imaging of VDPs in living cells. We believe that the
      present pKa shift switching strategy may facilitate the development of new
      fluorescent probes that are useful for a wide range of applications.

PMID- 29347819
TI  - Presence of Rigid Red Blood Cells in Blood Flow Interferes with the Vascular Wall
      Adhesion of Leukocytes.
AB  - The symptoms of many blood diseases can often be attributed to irregularities in
      cellular dynamics produced by abnormalities in blood cells, particularly red
      blood cells (RBCs). Contingent on the disease and its severity, RBCs can be
      afflicted with increased membrane rigidity as seen in malaria and sickle cell
      disease. Despite this understanding, little experimental work has been conducted
      toward understanding the effect of RBC rigidity on cellular dynamics in
      physiologic blood flow. Though many have computationally modeled complex blood
      flow to postulate how RBC rigidity may disrupt normal hemodynamics, to date,
      there lacks a clear understanding of how rigid RBCs affect the blood cell
      segregation behavior in blood flow, known as margination, and the resulting
      change in the adhesion of white blood cells (WBCs). In this work, we utilized an
      in vitro blood flow model to examine how different RBC rigidities and volume
      fractions of rigid RBCs impact cell margination and the downstream effect on
      white blood cell (WBC) adhesion in blood flow. Healthy RBC membranes were
      rigidified and reconstituted into whole blood and then perfused over activated
      endothelial cells under physiologically relevant shear conditions. Rigid RBCs
      were shown to reduce WBC adhesion by up to 80%, contingent on the RBC rigidity
      and the fraction of treated RBCs present in blood flow. Furthermore, the RBC core
      was found to be slightly expanded with the presence of rigid RBCs, by up to ~30%
      in size fully composed of rigid RBCs. Overall, the obtained results demonstrate
      an impact of RBC rigidity on cellular dynamics and WBC adhesion, which possibly
      contributes to the pathological understanding of diseases characterized by
      significant RBC rigidity.

PMID- 29347821
TI  - Fluorescence and Excited-State Conformational Dynamics of the Orange Carotenoid
      Protein.
AB  - The orange carotenoid protein (OCP) mediates nonphotochemical quenching (NPQ)
      mechanisms in cyanobacteria. A bound ketocarotenoid serves as a sensor of
      midvisible light intensity and as a quencher of phycocyanobilin excitons in the
      phycobilisome. The photochemical mechanism that triggers conversion of the
      protein from a resting, orange state (OCPO) to an active, red state (OCPR) after
      optical preparation of the S2 state of the carotenoid remains an open question.
      We report here that the fluorescence spectrum and quantum yield of the bound
      carotenoids in OCPO report important details of the motions that follow optical
      preparation of the S2 state. The fluorescence spectra from OCPO preparations
      containing 3'-hydroxyechinenone (3hECN) or canthaxanthin (CAN) are markedly
      mirror asymmetric with respect to the absorption line shape and more than an
      order of magnitude more intense than for carotenoids in solution. Further, 3hECN
      exhibits a narrower fluorescence line shape and a larger quantum yield than CAN
      because its excited-state motions are hindered by a hydrogen bonding interaction
      between the 3'-hydroxyl group on its beta2 ring and Leu37 in the N-terminal
      domain. These results show that large-amplitude motions of the carotenoid's beta2
      cyclohexene ring and of the conjugated polyene backbone initiate photochemistry
      in OCPO.

PMID- 29347825
TI  - Increasing condom usage for African-American and hispanic young fathers in a
      community based intervention.
AB  - OBJECTIVES: This paper investigates a community-based intervention for young
      fathers, FatherWorks, compared to care-as-usual, 24/7 Dads. We hypothesized that
      utilizing the FatherWorks intervention (a 15 session parenting intervention, 13
      session employment class, paid internship, case management, and access to
      behavioral health services) will assist in readiness to use condoms and increase
      condom usage, which may differ by race/ethnicity. METHODS: Eligible males (n =
      328) were enrolled into a Randomized Control Trial. Participants were 15-24 years
      old and had fathered one or more children with a female under the age of 21. A
      survey was taken at baseline and at 15 weeks following the intervention. RESULTS:
      Analyses of changes indicated that intervention participants improved from the
      pre-contemplation stage of condom usage towards contemplation, and from
      preparation to action. The pattern of improvement in the condom use stage of
      change was different in African-American versus Hispanic participants. Changes in
      condom use during last intercourse were not significant. CONCLUSIONS: Study
      findings indicate that FatherWorks is successful in increasing the intent to use
      condoms, with the effect manifesting differently in African-American and Hispanic
      young fathers. Future work with minority fathers indicates a need for cultural
      adaptation of the intervention.

PMID- 29347826
TI  - Acceptability of HIV cure-related trials: the challenges for physicians and
      people living with HIV (ANRS-APSEC).
AB  - Essential HIV cure-related clinical trials (HCRCT) have a potentially high-risk
      profile in terms of participants' health, which could hinder enrollment by people
      living with HIV (PLWH) and healthcare professionals (HP). The ANRS-APSEC survey
      is part of the IAS "Towards an HIV cure" initiative, which promotes
      multidisciplinary research for a safe, affordable and scalable cure. The study
      objectives were to understand the psychosocial mechanisms underlying PLWH and HP
      viewpoints about future HCRCT. Six focus group discussions (three with PLWH (n =
      21) and three with HP (n = 30)) were held in three French infectious disease
      units. From these, three perspectives on HCRCT were identified. The first
      involved beliefs and knowledge associating HCRCT with poorer health and quality
      of life for PLWH. The second concerned perceptions of HCRCT as a biological and
      epidemiological flashback to a situation when HIV infection was left
      uncontrolled. The third was characterized by aspects of historical HIV culture
      that embrace innovation.

PMID- 29347827
TI  - Psychological well-being and adherence to antiretroviral therapy among
      adolescents living with HIV in Zambia.
AB  - Physical and psychosocial changes during adolescence could influence the
      psychological well-being and adherence to antiretroviral therapy (ART) of
      adolescents living with HIV. However, few studies have assessed these two
      important issues in Zambia. This study aimed at addressing this gap by examining
      adolescents' depressive symptoms and ART adherence. This was a mixed-methods
      study conducted from April to July 2014. We recruited 200 adolescents, ages 15 to
      19, who were already aware of their HIV status. We measured depressive symptoms
      using the short form of the Center for Epidemiologic Studies Depression Scale,
      and self-reported three-day adherence to ART. We performed logistic regression
      analysis to identify factors associated with depressive symptoms and non
      adherence to ART. For qualitative data, we examined challenges over ART adherence
      using thematic analysis. Out of 190 adolescents, 25.3% showed high scores of
      depressive symptoms. Factors associated with depressive symptoms were
      unsatisfactory relationships with family (Adjusted Odds Ratio [AOR] 3.01; 95%
      Confidence Interval [CI] 1.20-7.56); unsatisfactory relationships with health
      workers (AOR 2.68; 95% CI 1.04-6.93); and experience of stigma (AOR 2.99; 95% CI
      1.07-8.41). Of all participants, 94.2% were taking ART, but 28.3% were non
      adherent. Factors associated with non-adherence to ART were loss of a mother (AOR
      3.00; 95% CI 1.05-8.58) and lack of basic knowledge about HIV (AOR 3.25; 95% CI
      1.43-7.40). Qualitative data identified the following challenges to ART
      adherence: management of medication, physical reactions to medicine, and
      psychosocial distress. The evidence suggests that depressive symptoms and non
      adherence to ART were priority issues in late adolescence in Zambia. Health
      workers should be aware of these issues, and the care and treatment services
      should be tailored to respond to age-specific needs.

PMID- 29347828
TI  - Change in HIV-related stigma in South Africa between 2004 and 2016: a cross
      sectional community study.
AB  - A critical component of an AIDS-free generation is to reduce HIV-related stigma.
      Previous research predicted that stigma would decline over time with increased
      contact with PLWH, understanding of the disease and availability of treatment.
      The aim of the research was to explore change in stigma over a 12-year period, by
      comparing data collected from two large cross-sectional samples from South
      African communities in 2004 (before the roll-out of antiretroviral treatment
      (ART)) and in 2016. Students recruited respondents according to criteria related
      to age, gender, race and area of living. A survey assessing moral judgement and
      interpersonal distance was used to assess personal and perceived community
      stigma. Responses to ten identical items used in the 2004 and 2016 data
      collection were compared. Personal stigma attached to HIV decreased significantly
      over time, except in respect of having close contact with PLWH, such as dating
      and befriending. Perceived community stigma remained high in all subgroups. It is
      argued that perceived community stigma contributes to high levels of internalised
      stigma among PLWH. Interventions should focus on helping PLWH to cope with
      perceived stigma and strategies to address stereotyping, which contributes to
      perceived community stigma.

PMID- 29347829
TI  - Biofilm community structure and the associated drag penalties of a groomed
      fouling release ship hull coating.
AB  - Grooming is a proactive method to keep a ship's hull free of fouling. This
      approach uses a frequent and gentle wiping of the hull surface to prevent the
      recruitment of fouling organisms. A study was designed to compare the community
      composition and the drag associated with biofilms formed on a groomed and
      ungroomed fouling release coating. The groomed biofilms were dominated by members
      of the Gammaproteobacteria and Alphaproteobacteria as well the diatoms Navicula,
      Gomphonemopsis, Cocconeis, and Amphora. Ungroomed biofilms were characterized by
      Phyllobacteriaceae, Xenococcaceae, Rhodobacteraceae, and the pennate diatoms
      Cyclophora, Cocconeis, and Amphora. The drag forces associated with a groomed
      biofilm (0.75 +/- 0.09 N) were significantly less than the ungroomed biofilm
      (1.09 +/- 0.06 N). Knowledge gained from this study has helped the design of
      additional testing which will improve grooming tool design, minimizing the growth
      of biofilms and thus lowering the frictional drag forces associated with groomed
      surfaces.

PMID- 29347830
TI  - An OMIC biomarker detection algorithm TriVote and its application in methylomic
      biomarker detection.
AB  - AIM: Transcriptomic and methylomic patterns represent two major OMIC data sources
      impacted by both inheritable genetic information and environmental factors, and
      have been widely used as disease diagnosis and prognosis biomarkers. MATERIALS &
      METHODS: Modern transcriptomic and methylomic profiling technologies detect the
      status of tens of thousands or even millions of probing residues in the human
      genome, and introduce a major computational challenge for the existing feature
      selection algorithms. This study proposes a three-step feature selection
      algorithm, TriVote, to detect a subset of transcriptomic or methylomic residues
      with highly accurate binary classification performance. RESULTS & CONCLUSION:
      TriVote outperforms both filter and wrapper feature selection algorithms with
      both higher classification accuracy and smaller feature number on 17
      transcriptomes and two methylomes. Biological functions of the methylome
      biomarkers detected by TriVote were discussed for their disease associations. An
      easy-to-use Python package is also released to facilitate the further
      applications.

PMID- 29347831
TI  - Racial/ethnic disparities in human papillomavirus vaccination initiation and
      completion among U.S. women in the post-Affordable Care Act era.
AB  - OBJECTIVE: To ascertain the magnitude and potential mechanisms of racial/ethnic
      disparities in initiating and completing the 3-dose human papillomavirus (HPV)
      vaccine among U.S. women in the post-Affordable Care Act era. DESIGN: Using 2015
      National Health Interview Survey data, we used logistic regression to estimate
      odds ratios (OR) and 95% confidence intervals (CI) for the association between
      race/ethnicity and HPV vaccination initiation and completion among black, Latina,
      Asian, and white U.S. women aged 18-31 years, adjusting for age and geographic
      region. We also examined the role of socioeconomic and health care factors in
      potentially explaining racial/ethnic disparities in HPV vaccine uptake and
      stratified our analyses by age (ages 18-22 and 23-31 years). RESULTS: The
      prevalence of HPV vaccination initiation and completion among U.S. women aged 18
      31 years overall was 35.4% and 22.7%, respectively. We observed no statistically
      significant difference in the odds of HPV vaccination initiation or completion by
      race/ethnicity among women aged 18-22 years, adjusting for age and geographic
      region. Among women aged 23-31 years, Latina ([odds ratio=] 0.59; [95% confidence
      interval:] 0.47, 0.76) and Asian (0.51; 0.34, 0.75) women had significantly lower
      adjusted odds of initiating HPV vaccination compared to white women. Further,
      relative to white women, black (0.46; 0.32, 0.67), Latina (0.45; 0.32, 0.64), and
      Asian (0.46; 0.28, 0.78) women had significantly lower adjusted odds of
      completing HPV vaccination. Adding socioeconomic factors to the models attenuated
      the HPV vaccination initiation adjusted odds ratios for Latina vs. white women
      and the HPV vaccination completion adjusted odds ratios for both black and Latina
      vs. white women. The inclusion of health care factors into the models did not
      further attenuate these odds ratios. CONCLUSION: Policies and programs that
      promote socioeconomic equity may mitigate HPV vaccination disparities between
      black and Latina women and white women. Additional research is needed to identify
      the drivers of HPV vaccination disparities between subgroups of Asian women and
      white women.

PMID- 29347832
TI  - Wire Placement in the Sustentaculum Tali Using a 2D Projection-Based Software
      Application for Mobile C-Arms: Cadaveric Study.
AB  - BACKGROUND: Indirect screw fixation of the sustentaculum tali in the lateral
      medial direction can be challenging due to the complex calcaneal anatomy. A novel
      2-dimensional (2D) projection-based software application detects Kirschner wires
      (K-wires) and visualizes their intended direction as a colored trajectory. The
      aim of this prospectively randomized cadaver study was to investigate whether the
      software would facilitate the indirect K-wire placement in the sustentaculum
      tali. METHODS: In 20 cadaver foot specimens, K-wires were placed indirectly in
      the sustentaculum tali by an experienced and an inexperienced surgeon, with and
      without using the application. Number of placement attempts, duration of
      procedure, fluoroscopy time, and number of individual fluoroscopy images were
      recorded. Each wire's position was analyzed in a 3-dimensional (3D) C-arm scan by
      an experienced blinded investigator. RESULTS: Use of the software by the
      inexperienced surgeon significantly reduced the number of placement attempts from
      3.2 to 1.2 ( P = .006). The application also reduced operating time, from 273 s
      to 199 s ( P = .15), and fluoroscopy time, from 41 s to 29 s ( P = .15). Using
      the software, the experienced surgeon had a longer operating time (139 s to 183
      s; P = .30), longer fluoroscopy time (5.6 s to 9.2 s; P = .17), and more
      individual fluoroscopy images (11.6 to 14.8; P = .30). Wire position did not show
      significant differences in both cases. CONCLUSION: During indirect K-wire
      placement in the sustentaculum tali, the software appeared to be a useful tool
      for the inexperienced surgeon. In our chosen study setting, the experienced
      surgeon did not benefit from the software. CLINICAL RELEVANCE: Possible
      indications for the software would be fractures of the proximal femur, sacrum,
      sacroiliac instabilities, vertebral bodies, scaphoid, Lisfranc joint, talus and
      calcaneus.

PMID- 29347833
TI  - How should we understand family-centred care?
AB  - What is family-centred care of a hospitalized child? A critical understanding of
      the concept of family-centred care is necessary if this widely preferred model is
      to be differentiated from other health care ideals and properly evaluated as
      appropriate to the care of hospitalized children. The article identifies
      distinguishable interpretations of family-centred care that can pull health
      professionals in different, sometimes conflicting directions. Some of these
      interpretations are not qualitatively different from robust interpretations of
      the ideals of parental participation, care-by-parent and partnership in care that
      are said to be the precursors of family-centred care. A prominent interpretation
      that regards the child and his or her family collectively as the 'unit of care'
      arguably arises from ambiguity and is significantly problematic as a model for
      the care of hospitalized children. Clinical practice driven by this
      interpretation can include courses of action that do not aim to do what will best
      promote a hospitalized child's welfare, and such cases will not be unusual. More
      broadly, this interpretation raises challenging questions about the
      responsibilities and authority of health professionals in relation to the
      interests of hospitalized children and their families.

PMID- 29347834
TI  - Acute Care Use for Ambulatory Care-Sensitive Conditions in High-Cost Users of
      Medical Care with Mental Illness and Addictions.
AB  - OBJECTIVE: The role of mental illness and addiction in acute care use for chronic
      medical conditions that are sensitive to ambulatory care management requires
      focussed attention. This study examines how mental illness or addiction affects
      risk for repeat hospitalization and/or emergency department use for ambulatory
      care-sensitive conditions (ACSCs) among high-cost users of medical care. METHOD:
      A retrospective, population-based cohort study using data from Ontario, Canada.
      Among the top 10% of medical care users ranked by cost, we determined rates of
      any and repeat care use (hospitalizations and emergency department [ED] visits)
      between April 1, 2011, and March 31, 2012, for 14 consensus established ACSCs and
      compared them between those with and without diagnosed mental illness or
      addiction during the 2 years prior. Risk ratios were adjusted (aRR) for age, sex,
      residence, and income quintile. RESULTS: Among 314,936 high-cost users, 35.9% had
      a mental illness or addiction. Compared to those without, individuals with mental
      illness or addiction were more likely to have an ED visit or hospitalization for
      any ACSC (22.8% vs. 19.6%; aRR, 1.21; 95% confidence interval [CI], 1.20-1.23).
      They were also more likely to have repeat ED visits or hospitalizations for the
      same ACSC (6.2% vs. 4.4% of those without; aRR, 1.48; 95% CI, 1.44-1.53). These
      associations were stronger in stratifications by mental illness diagnostic
      subgroup, particularly for those with a major mental illness. CONCLUSIONS: The
      presence of mental illness and addiction among high-cost users of medical
      services may represent an unmet need for quality ambulatory and primary care.

PMID- 29347835
TI  - Senna occidentalis (L.) Link and Senna hirsuta (L.) H. S. Irwin & Barneby:
      constituents of fruit essential oils and antimicrobial activity.
AB  - Senna occidentalis and S. hirsuta are mostly gathered from the wild for medicinal
      use and have a disagreeable odour when crushed. The volatile oils isolated from
      fresh fruits of S. occidentalis and S. hirsuta were subjected to gas
      chromatography (GC), gas chromatography-mass spectrometry (GC-MS) and
      antimicrobial assays. GC and GC-MS analyses permitted the identification of 58
      constituents. S. occidentalis oil was dominated by cyperene (10.8%), beta
      caryophyllene (10.4%), limonene (8.0%) and caryophyllene oxide (6.8%). The main
      components of S. hirsuta fruit oil were benzyl benzoate (24.7%), tau-cadinol
      (18.9%), 2,5-dimethoxy-p-cymene (14.6%) and beta-caryophyllene (5.1%). S.
      occidentalis fruit oil exhibited better antimicrobial activity (MIC 78-312
      MUg/mL) against Escherichia coli, Staphylococcus aureus, Bacillus subtilis and
      Aspergillus niger compared with S. hirsuta oil. The compositions and the
      activities of the fruit essential oils of S. occidentalis and S. hirsuta are
      reported for the first time.

PMID- 29347836
TI  - Strategies to overcome resistance mutations of Bruton's tyrosine kinase inhibitor
      ibrutinib.
AB  - Ibrutinib, as the first Bruton's tyrosine kinase (Btk) inhibitor, has been shown
      to have clinically significant activity in leukemias and lymphomas. However, the
      initially responsive tumors will develop resistance during the process of
      treatment in few patients. Here, we summarized the mechanism of acquired
      resistance and suggested the next-generation Btk inhibitors that override the
      target resistance. Moreover, the development of combination of selective
      antagonists or inhibitors targeting to multiple protein kinases have increased
      therapeutic potency to reduce the risk of the emergence of kinases inhibitor
      resistance. Thus, the reported combination of therapeutic drugs as an alternative
      therapy to overcome ibrutinib collapse or reduce the risk of the emergence of Btk
      inhibitor resistance also has been reviewed.

PMID- 29347837
TI  - Child Maltreatment and Physical Victimization: Does Heavy Drinking Mediate the
      Relationship?
AB  - Past studies examining the child maltreatment (CM)/victimization pathway have
      been limited by their focus on sexual victimization, narrow windows of
      assessment, and failure to examine gender differences. In the current study, we
      sought to examine (1) the impact of CM on physical victimization (PV)
      trajectories from adolescence to young adulthood and (2) the extent to which
      heavy drinking mediated the relationship between CM and later PV. Using three
      waves of the National Longitudinal Study of Adolescent to Adult Health, we found
      that CM was associated with a 69% greater odds of later PV for both genders,
      after the inclusion of control variables, and that the risk continued into
      adulthood. Further, heavy drinking was found to mediate the CM/victimization
      pathway at Wave I, but not at later waves. When mediation was examined separately
      for men and women, support for mediation was found for men and women. The current
      study suggests that CM represents a liability for interpersonal violence for both
      genders and highlights the importance of looking at victimization across time.

PMID- 29347838
TI  - Bacilsubteramide A, a new indole alkaloid, from the deep-sea-derived Bacillus
      subterraneus 11593.
AB  - From the deep-sea-derived bacterium Bacillus subterraneus 11593, a new indole
      alkaloid (1) was isolated along with three known compounds (2-4). By detailed
      analysis of its NMR spectroscopic data, and further by the theoretical ECD
      calculations, the absolute configuration of the new compound was determined to be
      (R)-N-[2-(3-hydroxy-2-oxoindolin-3-yl)ethyl]acetamide, and named bacilsubteramide
      A. All four isolates were tested for anti-allergic bioactivities; however, none
      exhibited positive effect (IC50 > 0.2 mM). Noteworthily, it is the first report
      on secondary metabolites from the bacterium B. subterraneus.

PMID- 29347839
TI  - Brain metastases epidemiology in a Tunisian population: trends and outcome.
AB  - AIM: We reported anatomo-clinical features of brain metastases (BMs) collected in
      a Tunisian medical oncology department. PATIENTS & METHODS: We retrospectively
      identified all cases of BM within a cohort of 7055 patients, treated for a
      histologically confirmed nonhematological cancer between 2000 and 2016. Data
      about age, sex and primary tumor were collected. RESULTS: Incidence was 1.9% and
      mean age was 54 years with a 1.24 sex ratio. BMs were symptomatic in 73.7% of
      cases after a median time of 16 months. A total of 73.4% patients receiving local
      therapy, 88% by whole brain radiation therapy and 21.6% had a metastasectomy.
      Lung and breast cancers were the primary in 80% of the BM. CONCLUSION: BM showed
      trends of young with underestimated incidence.

PMID- 29347840
TI  - Barriers and Enablers to the Implementation of School Wellness Policies: An
      Economic Perspective.
AB  - BACKGROUND: Local wellness policies (LWPs) are mandated among school systems to
      enhance nutrition/physical activity opportunities in schools. Prior research
      notes disparities in LWP implementation. This study uses mixed methods to examine
      barriers/enablers to LWP implementation, comparing responses by student body
      income. METHOD: Schools ( n = 744, 24 systems) completed an LWP implementation
      barriers/enablers survey. Semistructured interviews ( n = 20 random subsample)
      described barriers/enablers. Responses were compared by majority of lower (>=50%
      free/reduced-price meals; lower income [LI]) versus higher income (HI) student
      body. RESULTS: In surveys, LI and HI schools identified common barriers
      (parents/families, federal/state regulations, students, time, funding) and
      enablers (school system, teachers, food service, physical education
      curriculum/resources, and staff). Interviews further elucidated how staffing and
      funding served as enablers for all schools, and provide context for how and why
      barriers differed by income: time, food service (HI schools), and
      parents/families (LI schools). CONCLUSIONS: Findings support commonalities in
      barriers and enablers among all schools, suggesting that regardless of economic
      context, schools would benefit from additional supports, such as physical
      education and nutrition education resources integrated into existing curricula,
      additional funding, and personnel time dedicated to wellness programming. LI
      schools may benefit from additional funding to support parent and community
      involvement.

PMID- 29347841
TI  - Evolutionary Effect on the Embodied Beauty of Landscape Architectures.
AB  - According to the framework of evolutionary aesthetics, a sense of beauty is
      related to environmental adaptation and plasticity of human beings, which has
      adaptive value and biological foundations. Prior studies have demonstrated that
      organisms derive benefits from the landscape. In this study, we investigated
      whether the benefits of landscape might elicit a stronger sense of beauty and
      what the nature of this sense of beauty is. In two experiments, when viewing
      classical landscape and nonlandscape architectures photographs, participants
      rated the aesthetic scores (Experiment 1) and had a two-alternative forced choice
      aesthetic judgment by pressing the reaction button located near to (15 cm) or far
      from (45 cm) the presenting stimuli (Experiment 2). The results showed that
      reaction of aesthetic ratings for classical landscape architectures was faster
      than those of classical nonlandscape architectures. Furthermore, only the
      reaction of beautiful judgment of classical landscape architecture photograph was
      significantly faster when the reaction button was in the near position to the
      presenting photograph than those in the position of far away from the presenting
      photograph. This finding suggests a facilitated effect for the aesthetic
      perception of classical landscape architectures due to their corresponding
      components including water and green plants with strong evolutionary
      implications. Furthermore, this sense of beauty for classical landscape
      architectures might be the embodied approach to beauty based on the viewpoint of
      evolutionary aesthetics and embodied cognition.

PMID- 29347842
TI  - In vitro antioxidant potential and in vivo effects of Schinus terebinthifolia
      Raddi leaf extract in diabetic rats and determination of chemical composition by
      HPLC-ESI-MS/MS.
AB  - The present study investigated the in vitro and in vivo antioxidant potential and
      phytochemical composition of Schinus terebinthifolia, which is widely used in
      folk medicine for various therapeutic purposes. The in vitro analyses indicated
      that the hydroethanolic extract (HE) had 312.50 +/- 0.50 mg GAE/g of total
      phenols. It also presented anti-DPPH* and anti-ABTS*+ activity, reduced
      phosphomolybden and metal ions and blocked the bleaching of beta-carotene. The HE
      at concentrations of 3.0 and 2.0 MUg/mL had TRAP values of 2.223 +/- 0.018 and
      1.894 +/- 0.026 MUM Trolox, respectively. The HE increased the availability of
      antioxidants in plasma in treated animals in vivo. HPLC-ESI-MS/MS indicated the
      presence of 11 phenols: cumaric acid, (+)-catechin, myricetin-3-O-glicuronide,
      kaempferol-3-O-glucoside, myricetin, myricitrin, quercetin, gallic acid, methyl
      galate, pentagalloyl glucose and ethyl galate. Thus, S. terebinthifolia has
      potential for the prevention or treatment of diseases that are related to
      oxidative stress, such as diabetes mellitus.

PMID- 29347843
TI  - Combinatorial design and virtual screening of potent anti-tubercular
      fluoroquinolone and isothiazoloquinolone compounds utilizing QSAR and
      pharmacophore modelling.
AB  - The virulence of tuberculosis infections resistant to conventional combination
      drug regimens cries for the design of potent fluoroquinolone compounds to be used
      as second line antimycobacterial chemotherapeutics. One of the most effective in
      silico methods is combinatorial design and high throughput screening by a ligand
      based pharmacophore prior to experiment. The combinatorial design of a series of
      3850 fluoroquinolone and isothiazoloquinolone compounds was then screened
      virtually by applying a topological descriptor based quantitative structure
      activity relationship (QSAR) for predicting highly active congeneric quinolone
      leads against Mycobacterium fortuitum and Mycobacterium smegmatis. The predicted
      highly active congeneric hits were then subjected to a comparative study between
      existing lead sparfloxacin with fluoroquinolone FQ hits as well as ACH-702 with
      predicted active isothiazoloquinolones, utilizing pharmacophore modelling to
      focus on the mechanism of drug binding against mycobacterial DNA gyrase. Finally,
      68 compounds including 34 FQ and 34 isothiazoloquinolones were screened through
      high throughput screening comprising QSAR, the Lipinski rule of five and ligand
      based pharmacophore modelling.

PMID- 29347844
TI  - Docking analysis targeted to the whole enzyme: an application to the prediction
      of inhibition of PTP1B by thiomorpholine and thiazolyl derivatives.
AB  - PTP1b is a protein tyrosine phosphatase involved in the inactivation of insulin
      receptor. Since inhibition of PTP1b may prolong the action of the receptor, PTP1b
      has become a drug target for the treatment of type II diabetes. In the present
      study, prediction of inhibition using docking analysis targeted specifically to
      the active or allosteric site was performed on 87 compounds structurally
      belonging to 10 different groups. Two groups, consisting of 15 thiomorpholine and
      10 thiazolyl derivatives exhibiting the best prediction results, were selected
      for in vitro evaluation. All thiomorpholines showed inhibitory action (with IC50
      = 4-45 MUMU, Ki = 2-23 MUM), while only three thiazolyl derivatives showed low
      inhibition (best IC50 = 18 MUMU, Ki = 9 MUMU). However, free binding energy (E)
      was in accordance with the IC50 values only for some compounds. Docking analysis
      targeted to the whole enzyme revealed that the compounds exhibiting IC50 values
      higher than expected could bind to other peripheral sites with lower free energy,
      Eo, than when bound to the active/allosteric site. A prediction factor, E-
      (SigmaEo * 0.16), which takes into account lower energy binding to peripheral
      sites, was proposed and was found to correlate well with the IC50 values
      following an asymmetrical sigmoidal equation with r2 = 0.9692.

PMID- 29347845
TI  - Introductory paragraph.

PMID- 29347847
TI  - Combining cell and gene therapy to advance cardiac regeneration.
AB  - INTRODUCTION: The characterization of multipotent endogenous cardiac stem cells
      (eCSCs) and the breakthroughs of somatic cell reprogramming to boost
      cardiomyocyte replacement have fostered the prospect of achieving functional
      heart repair/regeneration. Areas covered: Allogeneic CSC therapy through its
      paracrine stimulation of the endogenous resident reparative/regenerative process
      produces functional meaningful myocardial regeneration in pre-clinical porcine
      myocardial infarction models and is currently tested in the first-in-man human
      trial. The in vivo test of somatic reprogramming and cardioregenerative non
      coding RNAs revived the interest in gene therapy for myocardial regeneration. The
      latter, together with the advent of genome editing, has prompted most recent
      efforts to produce genetically-modified allogeneic CSCs that secrete
      cardioregenerative factors to optimize effective myocardial repair. Expert
      opinion: The current war against heart failure epidemics in western countries
      seeks to find effective treatments to set back the failing hearts prolonging
      human lifespan. Off-the-shelf allogeneic-genetically-modified CSCs producing
      regenerative agents are a novel and evolving therapy set to be affordable, safe,
      effective and available at all times for myocardial regeneration to either
      prevent or treat heart failure.

PMID- 29347846
TI  - Poly (butylene adipate-co-butylene terephthalate) nanoparticles prepared by
      electrospraying technique for docetaxel delivery in ovarian cancer induced mice.
AB  - OBJECTIVE: Ovarian cancer is still a major cause of morbidity and mortality.
      Docetaxel (DTX) is one of the most notable cytotoxic agents for treatment of
      ovarian cancer. However, its side effects proposed considerable problems to the
      patients. SIGNIFICANCE: Polymeric nanoparticles (NPs) of poly (butylene adipate
      co-butylene terephthalate) (Ecoflex(r)), a biodegradable and biocompatible
      polymer, were prepared for the first time by the upgradeable electrospraying
      technique. METHODS: The formulation and procedure variables were optimized using
      Design Expert software, and effect of each variable on particle size, particle
      size distribution, drug entrapment efficiency, and drug release of the NPs were
      evaluated. Then, in vitro cytotoxicity, cellular uptake, X-ray diffraction
      pattern, and morphological characteristics of the optimized NPs were evaluated.
      Finally, in vivo efficacy of the DTX-loaded NPs was evaluated on tumor bearing
      nude mice. RESULTS: The optimum condition for production of NPs included voltage
      of 20 kV, 12 cm distance between electrodes, feeding rate of 1 mL/hr, polymer to
      drug ratio of 3:1, 1 w/v% of Pluronic-F127 and dichloromethane to dimethyl
      formamide ratio of 2.7:1. Fluorescent microscopy test showed the NPs were
      successfully up-taken by ovarian cancer cells. In vitro cytotoxicity test
      confirmed no cytotoxic effect caused by blank NPs, while cell viability of the
      DTX loaded NPs was significantly lower than the free DTX (p < .05). The NPs
      significantly enhanced anti-tumor efficacy of the drug in nude mice (p < .05).
      CONCLUSION: The Ecoflex(r) NPs could potentially provide a suitable alternative
      for currently available formulations of DTX.

PMID- 29347848
TI  - Role of topical oxytocin in improving vaginal atrophy in postmenopausal women: a
      randomized, controlled trial.
AB  - OBJECTIVE AND DESIGN: Prospective randomized controlled trial to test the
      effectiveness of topical oxytocin gel to improve vaginal atrophy in
      postmenopausal women. PATIENTS AND METHODS: A total of 140 postmenopausal women
      presenting with vaginal atrophy and who satisfied the inclusion and exclusion
      criteria were randomized into two groups each of 70 patients; they received
      intravaginal oxytocin gel or placebo gel for 30 days. Serum estrogen level,
      visual, colposcopic and histological vaginal examination were performed before
      and after treatment. RESULTS: Forty-seven out of 70 women in the oxytocin gel
      group improved after treatment and none in the placebo group (p = 0.001). Forty
      five participants in the oxytocin group and seven in the placebo group reported
      relief of dyspareunia (p = 0.001). Thirty-four participants in the oxytocin group
      and seven in the placebo group reported relief of soreness (p = 0.001). There was
      no significant difference between the circulating levels of estradiol in both
      groups before and after treatment (p = 0.4 and 0.6 for the oxytocin group and the
      placebo group, respectively). CONCLUSION: Oxytocin gel is useful in the
      restoration of the vaginal epithelium in cases of postmenopausal atrophic
      vaginitis. Further studies with a longer follow-up period are required to test
      the long-term effects of oxytocin as a treatment for vaginal atrophy.

PMID- 29347849
TI  - Joint pain within adult middle-aged women, attending a community clinic in a peri
      urban area in South Africa: a cross-sectional survey.
AB  - BACKGROUND: This study aimed to investigate the prevalence of joint pain in women
      between the ages of 40 and 64 years who attended a community clinic in the Free
      State to provide micro-information for health care planners. METHODS: A sample of
      convenience was utilized in the cross-sectional survey. Health care workers were
      recruited to conduct the survey. Outcome measures included the Community-Oriented
      Programme-For-The-Control-Of-Rheumatic-Disease questionnaire and European Quality
      of Life - 5 Dimensions health related quality of life measure. Descriptive
      statistics were calculated for categorical data and non-parametric tests for
      ordinal data. Quality Adjusted Life Years lost were based on the preference
      weights generated by the European Quality of Life - 5 Dimensions. RESULTS: One
      thousand three hundred seventy-six participants were enrolled. The prevalence of
      joint pain experienced in either the short or the long term was 62.1% (CI 59.5
      64.6%). The total number of Quality Adjusted Life Years lost in this sample was
      41.4, that is a rate of 3008.7 (CI 2740-3310) per 100,000. CONCLUSION:
      Epidemiological transition seems to be rapidly taking place in South Africa and
      the prevalence of joint pain is considerable. Primary health care systems should
      develop a cost-effective approach to manage and identify joint pain and improve
      the health-related quality of life of those living with this. Implications for
      Rehabilitation Prevalence of joint pain is considerable. Consume large amounts of
      health and social resources. A protocol for routine screening should be developed
      in community clinics. Cost-effective approach to manage joint pain should be
      identified to improve healthrelated quality of life of individuals living with
      joint pain.

PMID- 29347850
TI  - Feasibility of electrospray deposition for rapid screening of the cocrystal
      formation and single step, continuous production of pharmaceutical
      nanococrystals.
AB  - OBJECTIVES: This study employed electrospray deposition (ESD) for simultaneous
      synthesis and particle engineering of cocrystals. SIGNIFICANCE: Exploring new
      methods for the efficient production of cocrystals with desired particle
      properties is an essential demand. METHODS: The possibility of cocrystal
      formation by ESD was examined for indomethacin-saccharin, indomethacin
      nicotinamide, naproxen-nicotinamide, and naproxen-iso-nicotinamide cocrystals.
      Solutions of the drug and coformer at stoichiometric ratios were sprayed to a
      high electric field which caused rapid evaporation of the solvent and the
      formation of fine particles. The phase purity, size, and morphology of products
      were compared with reference cocrystals. Experiments were performed to evaluate
      the effects of stoichiometric ratio, concentration and solvent type on the
      cocrystal formation. Physical stability and dissolution properties of the
      electrosprayed cocrystals were also compared with reference cocrystals. RESULTS:
      ESD was found to be an efficient and rapid method to produce cocrystals for all
      studied systems other than indomethacin-nicotinamide. Pure cocrystals only formed
      at a specific drug:coformer ratio. The solvent type has a weak effect on the
      cocrystal formation and morphology. Electrosprayed cocrystals exhibited nano to
      micrometer sizes with distinct morphologies with comparable physical stability
      with reference cocrystals. Nanococrystals of indomethacin-saccharin with a mean
      size of 219 nm displayed a threefold higher dissolution rate than solvent
      evaporated cocrystal. CONCLUSION: ESD successfully was utilized to produce pure
      cocrystals of poorly soluble drugs with different morphologies and sizes ranging
      from nano to micrometer sizes in one step. This study highlighted the usefulness
      of ESD for simultaneous preparation and particle engineering of pharmaceutical
      cocrystals.

PMID- 29347851
TI  - The era of biofunctional biomaterials in orthopedics: what does the future hold?
AB  - INTRODUCTION: Titanium-based materials do not fulfill all of the requirements of
      orthopedic implants due to a mismatch in mechanical properties with bone which
      are prone to change during the course of bone growth. Biofunctional biomaterials
      are a new class of materials that show bioactivity and adaptability at any stage
      of bone growth. Areas covered: Different biofunctional biomaterials have evolved
      over time that can enhance calcium phosphate (CaP) precipitation, stimulate
      osteogenic differentiation, and can control osteoblast gene expression. These
      materials include metals or metal alloys, ceramics, polymers and biocomposites.
      Similarly, naturally-inspired nanomaterials and nanometer surface featured
      modified materials can enhance bone growth if created to match bone's unique
      micro to nano hierarchical structure. Nanoscale manipulation of existing
      biomaterials can incorporate antimicrobial properties which is desirable to
      prevent infection and failure of orthopedic devices. Expert commentary: Recent
      research trends in biofunctional biomaterials have focused to, first, understand
      the bone growth mechanism and, then, mimic natural bone architecture using
      biomaterials. Therefore, an enhanced understanding of material properties and
      tissue engineering principles will lead the way forward designing biofunctional
      biomaterials. In the future, the role of biofunctional biomaterials and
      orthopedic sensors will be more pronounced in terms of musculoskeletal disease
      prevention, diagnosis, and treatment.

PMID- 29347852
TI  - The patient categorisation tool: psychometric evaluation of a tool to measure
      complexity of needs for rehabilitation in a large multicentre dataset from the
      United Kingdom.
AB  - PURPOSE: This first psychometric evaluation of the Patient Categorisation Tool
      examined its properties as an instrument to measure complexity of needs in a
      mixed population of patients presenting for specialist neurorehabilitation.
      MATERIALS/METHODS: Analysis of a large multicentre cohort of patients (n = 5396)
      from the national clinical dataset representing 63 specialist rehabilitation
      services across England. Structural validity was examined using exploratory and
      confirmatory factor analysis. Concurrent and criterion-validity were tested
      through a priori hypothesized relationships with other validated measures of
      resource requirements and dependency. RESULTS: All but two items loaded strongly
      onto a single principal component with Cronbach's alpha 0.88. A total score of
      >=30 identified patients with complex (category A) needs with sensitivity 76% and
      specificity 75%. However, confirmatory factor analysis provided a better fit when
      the scale was split into two subscales - a 'Cognitive/psychosocial' and a
      'Physical' sub-scale (alpha 0.83 and 0.84, respectively). Moderate convergent and
      discriminant correlations were consistent with hypothesized relationships.
      CONCLUSIONS: The findings provide some overall support for the Patient
      Categorisation Tool as a unidimensional tool for measuring complexity of needs
      for neurorehabilitation, but the subscales may be more suitable for certain
      groups of patients. Further analysis is now required to evaluate its performance
      in different conditions. Implications for Rehabilitation A psychometrically
      robust tool for measuring the complexity of rehabilitation needs has potential
      value, both at an individual level for treatment planning, and at a population
      level for planning and commissioning rehabilitation services. The Patient
      Categorisation Tool now forms part of the United Kingdom national clinical
      dataset mandated by the National Health Service in England This psychometric
      analysis from a large national multicentre cohort representing a diverse range of
      conditions, provides evidence for its validity as a means to identity patients
      with complex rehabilitation needs requiring specialist rehabilitation.

PMID- 29347853
TI  - SAR thresholds for electromagnetic exposure using functional thermal dose limits.
AB  - BACKGROUND AND PURPOSE: To protect against any potential adverse effects to human
      health from localised exposure to radio frequency (100 kHz-3 GHz) electromagnetic
      fields (RF EMF), international health organisations have defined basic
      restrictions on specific absorption rate (SAR) in tissues. These exposure
      restrictions incorporate safety factors which are generally conservative so that
      exposures that exceed the basic restrictions are not necessarily harmful. The
      magnitude of safety margin for various exposure scenarios is unknown. This
      shortcoming becomes more critical for medical applications where the safety
      guidelines are required to be relaxed. The purpose of this study was to quantify
      the magnitude of the safety factor included in the current basic restrictions for
      various exposure scenarios under localised exposure to RF EMF. MATERIALS AND
      METHODS: For each exposure scenario, we used the lowest thermal dose (TD)
      required to induce acute local tissue damage reported in literature, calculated
      the corresponding TD-functional SAR limits (SARTDFL) and related these limits to
      the existing basic restrictions, thereby estimating the respective safety factor.
      RESULTS: The margin of safety factor in the current basic restrictions on 10 g
      peak spatial average SAR (psSAR10g) for muscle is large and can reach up to 31.2.
      CONCLUSIONS: Our analysis provides clear instructions for calculation of SARTDFL
      and consequently quantification of the incorporated safety factor in the current
      basic restrictions. This research can form the basis for further discussion on
      establishing the guidelines dedicated to a specific exposure scenario, i.e.
      exposure-specific SAR limits, rather than the current generic guidelines.

PMID- 29347854
TI  - A systematic review of health economic models and utility estimation methods in
      schizophrenia.
AB  - INTRODUCTION: There is a growing need for economic evaluations describing the
      disease course, as well as the costs and clinical outcomes related to the
      treatment of schizophrenia. Areas covered: A systematic review on studies
      describing health economic models in schizophrenia and a targeted literature
      review on utility mapping algorithms in schizophrenia were carried out. Models
      found in the review were collated and assessed in detail according to their type
      and various other attributes. Fifty-nine studies were included in the review.
      Modeling techniques varied from simple decision trees to complex simulation
      models. The models used various clinical endpoints as value drivers, 47% of the
      models used quality-adjusted life years, and eight percent used disability
      adjusted life years to measure benefits, while others applied various clinical
      outcomes. Most models considered patients switching between therapies, and
      therapeutic adherence, compliance or persistence. The targeted literature review
      identified four main approaches to map PANSS scores to utility values. Expert
      commentary: Health economic models developed for schizophrenia showed great
      variability, with simulation models becoming more frequently used in the last
      decade. Using PANSS scores as the basis of utility estimations is justifiable.

PMID- 29347855
TI  - Low-power bipolar radiofrequency ablation and vertebral augmentation for the
      palliative treatment of spinal malignancies.
AB  - AIM: To investigate the analgesic properties and the safety of low power bipolar
      radiofrequency ablation (RFA) performed with internally cooled electrodes and
      vertebral augmentation for the treatment of painful spinal malignancies.
      MATERIALS AND METHODS: Consent was waived for retrospective study participation.
      Review of electronic records identified 11 consecutive patients (6 females; 5
      males; mean age 61.3 +/- 11.6 years) with one-index painful spinal tumour, who
      were treated between June 2016 and October 2017 with bipolar RFA and vertebral
      augmentation. Patients were treated if they presented with focal pain (>=4/10 on
      a 0-10 visual analogic scale in the 24-h period) corresponding to a metastatic
      vertebral level on cross sectional imaging. The Wilcoxon test was used to
      evaluate the significance of the post-operative pain. RESULTS: Lumbar levels were
      treated in 72.7% cases; metastatic epidural involvement was noted in 81.8% cases;
      54.5% patients received associated treatments in addition to RFA, which was
      coupled to vertebral augmentation in all cases. Two (18.2%) complications were
      noted. Mean pain score measured at last clinical follow-up available (mean 1.9 +/
      1.4 months) was 3.5 +/- 2 (versus 7.8 +/- 1.1 at baseline; p <0.01).
      CONCLUSIONS: Low-power bipolar RFA performed with internally cooled electrodes
      and coupled to vertebral augmentation provides safe and effective early analgesia
      in patients affected by painful spinal malignancies.

PMID- 29347856
TI  - Systematic review of injuries in mixed martial arts.
AB  - OBJECTIVES: To assess injury rates in all mixed martial arts (MMA) studies.
      METHODS: Six online databases were searched until November 2017 including
      MEDLINE, EMBASE, CINAHL, Web of Science, PubMed, Google/Google Scholar and
      conference proceedings. All included studies were entered in Pub Med Single
      Citation Matcher and all citation chains followed. Abstracts and titles were
      assessed for relevance, data independently abstracted and risk of bias for all
      competition studies evaluated independently by two reviewers. RESULTS: There are
      data for 5,374 male and 108 female MMA fighters. For 2407 males the weighted
      average injury rate/1000Athletic Encounters (AE) was 246.4 and for one study of
      108 females 101.9. One study provided data by professional status: professionals
      135.5/1000AE and amateurs 71.0/1000AE. Reasons for stopping matches were
      knockout/technical knockout 173.9/1000AE for males and 175.9/1000AE for females,
      submission 228.6/1000AE, and referee's decision 98.2/1000AE. Losers can
      experience large amounts of trauma especially head trauma as matches terminate.
      Two studies of competitions provided personally conducted ringside assessments
      and both pre- and post-match examination results. The other studies reported
      retrospective assessments of fight records or videos or videos and scorecards.
      There are no studies of training injuries of professionals or injuries of
      amateurs or long-term follow-up of musculoskeletal injuries or neurological
      damage. Studies are limited to the US and Canada. There are no systematic reviews
      of newspaper or media accounts of fights to assess rates and numbers of injuries
      or mortality. The few published surveys and case reports markedly understate the
      worldwide situation. CONCLUSIONS: There are high rates of trauma in MMA. The
      authorities who regulate MMA and referees and physicians who monitor MMA fighters
      have an inadequate database to guide their work. Researchers need to adopt the
      same set of complete definitions of all possible injuries and measure the high
      and early rate of neurological damage.

PMID- 29347857
TI  - Mulberry leaves and their potential effects against cardiometabolic risks: a
      review of chemical compositions, biological properties and clinical efficacy.
AB  - CONTEXT: Cardiometabolic risks are regarded as the crucial factors associated
      with type 2 diabetes (T2DM) and cardiovascular diseases (CVD). Regarding an
      increased attention to medicinal plants in the current healthcare system, the
      effects of mulberry (Morus spp., Moraceae) leaves on cardiometabolic risks have
      been consecutively considered in scientific research. OBJECTIVE: The present
      review compiles and summarizes the chemical compositions, biological properties
      and clinical efficacy of mulberry leaves that are related to the amelioration of
      cardiometabolic risks. METHODS: Published English literature from the PubMed,
      Science Direct and Google Scholar databases was searched by using 'mulberry
      leaves' 'Morus spp.', 'hyperglycemia', 'hyperlipidemia', 'obesity',
      'hypertension', 'oxidative stress', 'atherosclerosis' and 'cardiovascular
      diseases' as the keywords. The relevant articles published over the past two
      decades were identified and reviewed. RESULTS: Mulberry leaves contain numerous
      chemical constituents. 1-Deoxynojirimycin (DNJ), phenolics and flavonoids are the
      prominent functional compounds. Preclinical and clinical studies showed that
      mulberry leaves possessed various beneficial effects against cardiometabolic
      risks, including antihyperglycaemic, antihyperlipidaemic, antiobesity,
      antihypertensive, antioxidative, anti-inflammatory, anti-atherosclerotic and
      cardioprotective effects. CONCLUSIONS: Mulberry leaves could be a promising
      therapeutic option for modulating cardiometabolic risks. However, further
      investigations should be performed to substantiate the potential of mulberry
      leaves in practical uses.

PMID- 29347858
TI  - Where are we with injectables against HIV infection and what are the remaining
      challenges?
AB  - INTRODUCTION: Drug adherence has been a recurring issue in the field of HIV
      treatment, and low treatment adherence is typically associated with emergence of
      drug resistance, treatment failure and increased risks of transmission.
      Injectable antiretroviral drugs offer a unique opportunity to counter this issue
      for the treatment of HIV-positive individuals. In addition, injectables offer a
      remarkable opportunity to reduce new HIV infections, if applied in the context of
      both treatment-as-prevention and pre-exposure prophylaxis. Areas covered:
      Researchers and drug companies are developing long-acting agents that possess
      long biological half-life and excellent pharmacokinetic profiles that can be
      administered intramuscularly, intravenously, or subcutaneously. These long-acting
      injectables are categorized as drugs that target different steps of HIV
      replication cycle or monoclonal antibodies that target HIV entry. Expert
      commentary: Injectables against HIV have the potential to revolutionize the fight
      against HIV by facilitating both treatment and prevention in a wide variety of
      clinical settings. Several challenges remain including the identification of
      potent two-drug combinations of drugs that can be formulated as injectables, and
      thorough drug-drug interaction studies with a broad variety of medications.
      Finally we believe that the healthcare benefits of injectables will require
      regulatory changes to allow self-injection before they reach their full
      potential.

PMID- 29347859
TI  - PACTRIMS 2017.

PMID- 29347860
TI  - Alteration of auditory function in type 2 diabetic and pre-diabetic patients.
AB  - BACKGROUND: The association between type 2 diabetes mellitus (T2DM) and hearing
      loss has not been fully investigated and there is little information on the
      effects of pre-diabetes on alterations in auditory function in Chinese subjects.
      METHODS: The study recruited 51 patients with T2DM, 55 patients with pre-diabetes
      and 43 control subjects. Auditory function was assessed by pure tone audiometry
      (PTA) tests and distortion product of otoacoustic emissions (DPOAEs). Tinnitus
      symptoms were recorded using a medical history questionnaire. RESULTS: A
      significantly larger number of patients with T2DM (45.1%) were affected by
      hearing loss, compared to pre-diabetes patients (23.6%; p = .04) and control
      subjects (25.6%; p = .02), as assessed by PTA. There was no significant
      difference in PTA between the number of pre-diabetes patients and control
      subjects. In contrast, mean DPOAEs amplitudes of the pre-diabetes patients were
      significantly lower than of the control subjects, at all frequencies
      investigated, except 0.75 kHz. A significantly greater number of pre-diabetes
      patients reported tinnitus symptoms. CONCLUSIONS: Diabetes is associated with
      bilateral sensorineural hearing loss, especially at high frequencies. While pre
      diabetes is not necessarily associated with significant hearing loss, there may
      be cochlear malfunction, as indicated by DPOAEs. Thus, patients with pre-diabetes
      who have tinnitus may benefit from DPOAEs and PTA tests.

PMID- 29347861
TI  - Positive emotional attention bias in young children with symptoms of ADHD.
AB  - Children with attention-deficit/hyperactivity disorder (ADHD) often experience
      emotional dysregulation. Dysregulation can arise from heightened attention to
      emotional stimuli. Emotional attention biases are associated with a number of
      adverse socioemotional outcomes including reward sensitivity and externalizing
      behaviors. As reward sensitivity and externalizing behaviors are common in
      children with ADHD, the aim of the current study was to determine whether
      emotional attention biases are evident in young children with clinically
      significant ADHD symptoms. To test this, children with (n = 18) and without (n =
      15) symptoms of ADHD were tested on a Dot Probe task. Provided recent evidence
      that emotional attention biases are attenuated by sleep, the task was performed
      before and after overnight sleep. Children with ADHD symptoms displayed positive,
      but not negative, attention biases at both time points, whereas typically
      developing children did not preferentially attend toward or away from positive or
      negative stimuli. Sleep did not alter attention biases in either group.
      Collectively, these results indicate that children with ADHD symptoms have
      stable, positive attention biases.

PMID- 29347862
TI  - Survey of the awareness of adult rheumatologists regarding transitional care for
      patients with juvenile idiopathic arthritis in Japan.
AB  - OBJECTIVES: To understand the current status of adult rheumatology care for
      patients who had previously had juvenile idiopathic arthritis (JIA) (excluding
      systemic JIA), and to identify issues interfering with the transition from
      pediatric to adult care in Japan. METHODS: Questionnaire-based survey among 30
      adult rheumatologists. RESULTS: Eighty-seven percent of adult rheumatologists
      responded that they had provided medical care to adults who had had JIA; 44% of
      them had felt hesitation or anxiety when providing such care. The reasons for
      this included lack of independence of the patients, lack of knowledge and
      experience among adult rheumatologists, and lack of preparation for accepting
      such patients. Many adult rheumatologists believed that the timing of transition
      from pediatric to adult rheumatology care must be considered based on therapeutic
      regimens or clinical conditions/disease states, not solely chronological age. A
      majority of adult rheumatologists showed great interest in transitional care for
      JIA patients and desired to communicate better with pediatric rheumatologists.
      CONCLUSION: Transitional care for JIA patients is not sufficiently developed in
      Japan. Education and advocate campaign of transitional care is required for adult
      rheumatologists as well as patients and their parents.

PMID- 29347864
TI  - Dense Breast Notification Laws: Impact on Downstream Imaging After Screening
      Mammography.
AB  - Dense breast tissue is a common finding that decreases the sensitivity of
      mammography in detecting cancer. Many states have recently enacted dense breast
      notification (DBN) laws to provide patients with information to help them make
      better-informed decisions about their health. To test whether DBN legislation
      affected the probability of screening mammography follow-up by ultrasound and
      magnetic resonance imaging (MRI), we examined the proportion of times screening
      mammography was followed by ultrasound or MRI for a series of months pre- and
      post-legislation. The subjects were women aged 40 to 64 years, covered by private
      health insurance, undergoing screening mammography from 2007 to 2014. Except for
      Hawaii, Maryland, and New York, DBN legislation significantly increased the
      probability of ultrasound follow-up in all states that implemented DBN
      legislation before December 2014. It also increased the probability of MRI follow
      up in California, North Carolina, Pennsylvania, and Texas. The financial and
      access consequences merit further study.

PMID- 29347863
TI  - An Intervention to Improve Physical Function and Caregiver Perceptions in Family
      Caregivers of Persons With Heart Failure.
AB  - OBJECTIVE: This randomized controlled trial was conducted to determine whether a
      12-week home-based aerobic and resistance exercise program would improve physical
      function and caregiving perceptions among family caregivers (FCGs) of persons
      with heart failure. METHOD: Overall, 127 FCGs were randomized to one of three
      groups: usual care attention control (UCAC), psychoeducation only (PE), and
      psychoeducation plus exercise (PE + EX). Physical function measures (6-min walk
      test, handgrip, and upper and lower strength) and caregiving perceptions (Bakas
      Caregiving Outcomes Scale) were obtained at baseline and at 6 months. RESULTS:
      FCGs in the PE + EX showed significant improvement in 6-min walk distance ( p =
      .012), handgrip, and lower extremity strength compared with the PE and UCAC
      groups. The combined group had the greatest improvement in caregiver perceptions
      ( p < .001). CONCLUSION: FCGs in the PE + EX group improved the most in physical
      function and caregiver perception outcomes. Directions for future research are
      provided.

PMID- 29347865
TI  - The Influence of Multimorbidity on Leading Causes of Death in Older Adults With
      Cognitive Impairment.
AB  - OBJECTIVE: The aim of this study is to evaluate the relationship of leading
      causes of death with gradients of cognitive impairment and multimorbidity.
      METHOD: This is a population-based study using data from the linked 1992-2010
      Health and Retirement Study and National Death Index ( n = 9,691). Multimorbidity
      is defined as a combination of chronic conditions, functional limitations, and
      geriatric syndromes. Regression trees and Random Forest identified which
      combinations of multimorbidity associated with causes of death. RESULTS:
      Multimorbidity is common in the study population. Heart disease is the leading
      cause in all groups, but with a larger percentage of deaths in the mild and
      moderate/severe cognitively impaired groups than among the noncognitively
      impaired. The different "paths" down the regression trees show that the
      distribution of causes of death changes with different combinations of
      multimorbidity. DISCUSSION: Understanding the considerable heterogeneity in
      chronic conditions, functional limitations, geriatric syndromes, and causes of
      death among people with cognitive impairment can target care management and
      resource allocation.

PMID- 29347866
TI  - Effects of cereal bar containing polydextrose on subjective feelings of appetite
      and energy intake in overweight adults over 15 d.
AB  - The effects of 15 d polydextrose (16.7 g) consumption on energy intake (EI) and
      appetite feelings were investigated. Overweight adults consumed a polydextrose
      bar or a control-bar matched in energy content as a midmorning snack for 15
      consecutive days in a single-blind, randomised, crossover design. The two 15-d
      intervention periods were separated by a 15-d washout period. On the day 1 and
      the day 15 of each intervention period, energy intake (primary outcome) and
      appetite feelings (secondary outcome) were assessed. There were not significant
      main effects of the day, type of bar, or their interaction for EI (at lunchtime
      test meal, at rest of the day, or at total daily) or subjective feelings (hunger,
      desire to eat, fullness, and prospective food consumption) during the satiation
      and satiety periods. The results showed the consumption of polydextrose-bar
      during 15 d did not significantly affect energy intake and subjective feelings of
      appetite in overweight adults.

PMID- 29347867
TI  - The Mediterranean Diet: its definition and evaluation of a priori dietary indexes
      in primary cardiovascular prevention.
AB  - We have analysed the definition of Mediterranean Diet in 28 studies included in
      six meta-analyses evaluating the relation between the Mediterranean Diet and
      primary prevention of cardiovascular disease. Some typical food of this dietary
      pattern like whole cereals, olive oil and red wine were taken into account only
      in a few a priori indexes, and the dietary pattern defined as Mediterranean
      showed many differences among the studies and compared to traditional
      Mediterranean Diet of the early 1960s. Altogether, the analysed studies show a
      protective effect of the Mediterranean Diet against cardiovascular disease but
      present different effects against specific conditions as cerebrovascular disease
      and coronary heart disease. These different effects might depend on the
      definition of Mediterranean Diet and the indexes of the adhesion to the same one
      used. To compare the effects of the Mediterranean Diet against cardiovascular
      disease, coronary heart disease and stroke a univocal model of Mediterranean Diet
      should be established as a reference, and it might be represented by the Modern
      Mediterranean Diet Pyramid. The a priori index to evaluate the adhesion to
      Mediterranean Diet might be the Mediterranean-Style Dietary Pattern Score that
      has some advantages in comparison to the others a priori indexes.

PMID- 29347868
TI  - Differential White Matter Regional Alterations in Motor Subtypes of Early Drug
      Naive Parkinson's Disease Patients.
AB  - BACKGROUND: Parkinson's disease (PD) can be classified into tremor dominant (TD)
      and postural instability and gait difficulty (PIGD) subtypes with TD considered
      as the benign subtype. The neural alterations of the 2 subtypes in the early
      stages before administration of medications remain elusive. OBJECTIVE: This study
      assessed the subtype-related white matter (WM) microstructural features in newly
      diagnosed and drug-naive PD patients from the Parkinson's Progression Markers
      Initiative (PPMI). METHODS: Sixty-five early PDs with stable subtypes (52 TD and
      13 PIGD patients) and 61 controls underwent diffusion tensor imaging (DTI)
      scanning and clinical assessment. Tract-based special statistics (TBSS), graph
      theoretical and network-based analyses were used to compare WM regional and
      network features between groups. RESULTS: No differences in disease stages and
      duration were found between the 2 patient groups. TD patients showed increased
      fractional anisotropy (FA), but decreased radial and axial diffusivities (RD and
      AD) in several projection, association, and commissural tracts, compared with
      PIGD patients and controls. Motor severity had mild-to-moderate correlations with
      FA and RD of the corpus callosum (genu) in TD, but strong correlations with FA
      and RD of multiple association tracts in PIGD. Conversely, no significant network
      changes were noted. CONCLUSIONS: TD patients showed regionally increased FA but
      decreased diffusivities, implying neural reorganization to compensate PD
      pathology in early stages. PIGD patients, despite having similar disease stages
      and duration, exhibited more WM degradation. These results demonstrate
      differential WM regional features between the 2 subtypes in early PD and support
      the notion of TD being a benign subtype.

PMID- 29347869
TI  - Social Support Networks and Quality of Life of Rural Men in a Context of Marriage
      Squeeze in China.
AB  - A significant number of rural Chinese men are facing difficulties in finding a
      spouse and may fail to ever marry due to a relative scarcity of women in the
      adult population. Research has indicated that marriage squeeze is a stressful
      event which is harmful to men's quality of life, and also weakens their social
      support networks. Using data collected in rural Chaohu city, Anhui, China, this
      study explores the effects of social support networks on quality of life of rural
      men who experience a marriage squeeze. The results indicate that the size of
      social contact networks is directly and positively associated with the quality of
      life of marriage-squeezed men, and moderate the negative effect of age on quality
      of life. Having no or limited instrumental support network and social contact
      network are double-edged swords, which have direct negative associations with the
      quality of life of marriage-squeezed men, and have moderate effects on the
      relationship between marriage squeeze and quality of life.

PMID- 29347870
TI  - Incorporating living from the heart into medical education.
AB  - Medical training poses many challenges to trainees' wellbeing. To address the
      impact of learning in a high turnover, high volume, acute care setting in the
      General Internal Medicine Clinical Teaching Unit, the Chief Medical Resident, in
      this personal account, shares how she and the Spiritual Care Practitioner united
      to form an innovative partnership. The introduction of the skills of spiritual
      care practitioners, generally referred to patients and families, to support
      medical students and residents resulted in the co-development and co
      implementation of a unique, reflective, one-hour session. The objective was to
      create a protected space and time to discuss the impact of training and clinical
      experiences on medical trainees' wellbeing, in the context of "living from the
      heart".

PMID- 29347871
TI  - Commentary on "Regulatory Support Improves Subsequent IRB/REC Approval Rates in
      Studies Initially Deemed Not Ready for Review: A CTSA Institution's Experience".
AB  - In response to researcher concerns a number of initiatives have been developed to
      support individual researchers seeking ethics review and approval. In this issue,
      Sonne et al. (2017) outline an example of an intervention to support researchers,
      which they refer to as a Regulatory Knowledge Support (RKS) service. While the
      study points to potential benefits, other studies have not had the desired impact
      on key performance measures. There is a need to develop a community of practice
      and expand the burgeoning evidence base regarding what interventions work, for
      whom, and under what circumstances. Advancing the research agenda requires: the
      development of theoretical models for intervention design and evaluation;
      developing consensus on key data for collection and measures of effectiveness;
      conducting evaluations using the strongest possible study designs, and;
      publishing the findings of evaluations.

PMID- 29347873
TI  - Students with an autonomous role in hospital care - patients perceptions.
AB  - BACKGROUND: There have been calls to enhance clinical education by strengthening
      supported active participation (SAP) of medical students in patient care. This
      study examines perceived quality of care when final-year medical students are
      integrated in hospital ward teams with an autonomous relationship toward their
      patients. METHODS: We established three clinical education wards (CEWs) where
      final-year medical students were acting as "physician under supervision". A
      questionnaire-based mixed-method study of discharged patients was completed in
      2009-15 using the Picker Inpatient Questionnaire complemented by specific
      questions on the impact of SAP. Results were compared with matched pairs of the
      same clinical specialty from the same hospital (CG1) and from nationwide
      hospitals (CG2). Patients free-text feedback about their hospital stay was
      qualitatively evaluated. RESULTS: Of 1136 patients surveyed, 528 (46.2%) returned
      the questionnaire. The CEWs were highly recommended, with good overall quality of
      care and patient-physician/student-interaction, all being significantly (p <
      0.001) higher for the CEW group while experienced medical treatment success was
      similar. Patient-centeredness of students was appreciated by patients as a
      support to a deeper understanding of their condition and treatment. CONCLUSION:
      Our study indicates that SAP of final-year medical students is appreciated by
      patients with high overall quality of care and patient-centeredness.

PMID- 29347875
TI  - Universal informative CpG sites for inferring tumor purity from DNA methylation
      microarray data.
AB  - Tumor purity is an intrinsic property of tumor samples and potentially has severe
      impact on many types of data analysis. We have previously developed a statistical
      method, InfiniumPurify, which could infer purity of a tumor sample given its
      tumor type (available in TCGA) or a set of informative CpG (iDMC) sites. However,
      in many clinical practices, researchers may focus on a specific type of tumor
      samples that is not included in TCGA, and samples which are too few to identify
      reliable iDMCs. This greatly restricts the application of InfiniumPurify in
      cancer research. In this paper, we proposed an updated version of InfiniumPurify
      (termed as uiInfiniumPurify) through identifying a universal set of iDMCs
      (uiDMCs) and redesigning the algorithm to determine hyper- and hypo-methylation
      status of each uiDMC. Through the application, we estimated tumor purities of
      8830 tumor samples from TCGA. Result shows that our estimates are highly
      consistent with those by other available methods. Consequently, the updated
      uiInfiniumPurify, can be applied to a single sample (or a few samples) of
      interest whose tumor type is not included in TCGA. This characteristic will
      greatly broaden the application of uiInfiniumPurify in cancer research.

PMID- 29347877
TI  - Part-set cueing impairment & facilitation in semantic memory.
AB  - The present study explored the influence of part-set cues in semantic memory
      using tests of "free" recall, reconstruction of order, and serial recall. Nine
      distinct categories of information were used (e.g., Zodiac signs, Harry Potter
      books, Star Wars films, planets). The results showed part-set cueing impairment
      for all three "free" recall sets, whereas part-set cueing facilitation was
      evident for five of the six ordered sets. Generally, the present results parallel
      those often observed across episodic tasks, which could indicate that similar
      mechanisms contribute to part-set cueing effects in both episodic and semantic
      memory. A novel anchoring explanation of part-set cueing facilitation in order
      and spatial tasks is provided.

PMID- 29347876
TI  - Risk of overhydration and low lean tissue index as measured using a body
      composition monitor in patients on hemodialysis: a systemic review and meta
      analysis.
AB  - Overhydration and sarcopenia, related to an individual's nutritional status, have
      been associated with increased cardiovascular mortality and poor prognosis in
      patients on hemodialysis. The purpose of this study was to investigate the
      prediction of overhydration and sarcopenia on mortality in patients on
      hemodialysis using a body composition monitor. We conducted a systematic review
      and meta-analysis using a random-effects model. We searched the Cochrane Central
      Register, OVID MEDLINE, EMBASE and PubMed databases for all studies published
      prior to December 9, 2016 and reviewed the reference lists of relevant reviews,
      registered trials and relevant conference proceedings. The overhydration group
      (fluid excess, >15% vs. the normohydration group) and the low lean tissue index
      group ( <10%) were compared with a reference group. Six trials, consisting of
      29,469 patients, were included in the pooled analysis. The pooled hazard ratio
      for overall survival of the overhydration group, compared with the reference
      normohydration group was 1.798 (95% confidence interval [CI]: 1.53-2.804, p =
      .001). The hazard ratio for mortality in the low lean tissue index group was
      1.533 (95% CI, 1.411-1.644; p = .001) in the random-effects model. The results
      from the most recent study showed the greatest heterogeneity in the sensitivity
      analysis. Low lean tissue index and overhydration, measured using a body
      composition monitor, were associated with a high mortality rate in patients on
      hemodialysis.

PMID- 29347878
TI  - The effect of aging on the (mis)perception of intentionality - an ERP study.
AB  - Despite the accumulated knowledge on moral decision-making in the early stages of
      development, empirical evidence is still limited in the old-aged adults. The
      current study contributes to unveil the neural correlates of judgments of moral
      transgressions as a function of aging, by examining the temporal dynamics of
      neural activation elicited by intentional and accidental harmful actions in three
      groups of healthy participants: young adults (18-35), adults (40-55), and older
      adults (60-75). Older adults were slower and less accurate in rating
      intentionality, compared to the younger groups. In ERP analysis, the older group
      showed increased P2 amplitude, which was predicted by poorer performance on
      neuropsychological tests. Reduced amplitudes were found on critical ERP
      components to moral cognition (N2 and LPP), namely while processing intentional
      harmful scenarios. Older adults seem to allocate more attentional resources (P2)
      to the task, probably to compensate the age-related decline in executive
      functioning, while younger groups show a pronounced negativity while detecting
      harm (N2) and increased neural activation to encode the intentions behind the
      acts (LPP).

PMID- 29347879
TI  - The Listener Sets the Tone: High-Quality Listening Increases Attitude Clarity and
      Behavior-Intention Consequences.
AB  - We examined how merely sharing attitudes with a good listener shapes speakers'
      attitudes. We predicted that high-quality (i.e., empathic, attentive, and
      nonjudgmental) listening reduces speakers' social anxiety and leads them to delve
      deeper into their attitude-relevant knowledge (greater self-awareness). This,
      subsequently, differentially affects two components of speaker's attitude
      certainty by increasing attitude clarity, but not attitude correctness. In
      addition, we predicted that this increased clarity is followed by increased
      attitude- expression intentions, but not attitude- persuasion intentions. We
      obtained consistent support for our hypotheses across five experiments (including
      one preregistered study), manipulating listening behavior in a variety of ways.
      This is the first evidence that an interpersonal variable, unrelated to the
      attitude itself, can affect attitude clarity and its consequences.

PMID- 29347880
TI  - Functions of Utopia: How Utopian Thinking Motivates Societal Engagement.
AB  - Images of ideal societies, utopias, are all around us; yet, little is known of
      how utopian visions affect ordinary people's engagement with their societies. As
      goals for society, utopias may elicit processes of collective self-regulation, in
      which citizens are critical of, or take action to change, the societies they live
      in. In three studies, we investigated the psychological function of utopian
      thinking. In Study 1, measured utopianism was correlated with the activation of
      three utopian functions: change, critique, and compensation. In Study 2, primed
      utopian thinking consistently enhanced change and criticism intentions. Study 3
      also provided evidence that mental contrasting-first imagining a utopian vision
      and then mentally contrasting the current society to this vision-underlies the
      facilitative effect of utopian thinking on societal engagement.

PMID- 29347881
TI  - Being an agent of change: a student's view of the UK's first yearlong
      Longitudinal Integrated Clerkship (LIC).

PMID- 29347882
TI  - Third Shade of Simulation.

PMID- 29347883
TI  - Pulmonary Laser Metastasectomy by 1318-nm Neodymium-Doped Yttrium-Aluminum Garnet
      Laser: A Retrospective Study About Laser Metastasectomy of the Lung.
AB  - BACKGROUND: The lungs are among the first organ affected by remote metastases
      from many primary tumors. The surgical resection of isolated pulmonary metastases
      represents an important and effective element of therapy. This is a retrospective
      study about our entire experience with pulmonary resection for metastatic cancer
      using 1318-nm neodymium-doped yttrium-aluminum garnet laser. METHOD: In this
      single-institution study, we retrospectively analyzed a group of 209 patients
      previously treated for primary malignant solid tumors. We excluded 103 patients.
      The number and location of lesions in the lungs was determined using chest
      computed tomography and positron emission tomography-computed tomography.
      Disseminated malignancy was excluded. All pulmonary laser resections are
      performed via an anteroaxillary muscle-sparing thoracotomy. All lesions were
      routinely removed by laser with a small (5-10 mm) margin of the healthy lung.
      Patients received systematic lymph node sampling with intraoperative smear
      cytology of sampled lymph nodes. RESULTS: Mortality at 2 years from the first
      surgery is around 20% (10% annually). This value increases to 45% in the third
      year. The estimated median survival for patients who underwent the first surgery
      is reported to be approximately 42 months. CONCLUSION: Our results show that
      laser resection of lung metastases can achieve good result, in terms of radical
      resection and survival, as conventional surgical metastasectomy. The great
      advantage is the possibility of limiting the damage to the lung. Stapler
      resection of a high number of metastases would mutilate the lung.

PMID- 29347884
TI  - Differential mRNA expression of inflammasome genes NLRP1 and NLRP3 in abdominal
      aneurysmal and occlusive aortic disease.
AB  - NLRP1 and NLRP3 inflammasomes might differentially mediate the chronic
      inflammatory response in abdominal aortic aneurysm (AAA) and aortic occlusive
      disease (AOD). We measure differential relative gene expression of NLRP1 and
      NLRP3 inflammasomes in aortic tissues from 30 patients undergoing AAA open repair
      compared to aortic biopsies from 30 patients undergoing surgery to treat AOD.
      Aortic wall samples from autopsy without aortic disease were used as controls.
      NLRP3 was overexpressed in patients with AAA and AOD (RQ 1.185 +/- 0.15, and
      1.098 +/- 0.05, respectively) compared to donors (RQ 1.001 +/- 0.08) (OR 2.8, 95%
      CI 1.2-4.3, p < 0.05 for AAA and OR 2.1, 95% CI 1.1-3.8, p < 0.05 for AOD). NLRP1
      gene expression was significantly upregulated in patients with AOD (RQ 1.197 +/-
      0.09). Meanwhile, NLRP1 was normal expressed in AAA (RQ 1.003 +/- 0.07) as well
      as in autopsy aortic specimens (RQ 1.005 +/- 0.11). Enhanced NLRP1 expression in
      AOD was even significant when compared to AAA (OR 2.3, 95% CI 1.2-3.3, p < 0.05)
      or controls (OR 2.2, 95% CI 1.1-3.1, p < 0.05). According to our findings, NLRP3
      could be involved in the common etiology of AAA and AOD, whereas NLRP1 appears to
      have a specific role in AOD development.

PMID- 29347885
TI  - Preparation of affordable and multifunctional clay-based ceramic filter matrix
      for treatment of drinking water.
AB  - Affordable clay-based ceramic filters with multifunctional properties were
      prepared using low-cost and active ingredients. The characterization results
      clearly revealed well crystallinity, structural elucidation, extensive porosity,
      higher surface area, higher stability, and durability which apparently enhance
      the treatment efficiency. The filtration rates of ceramic filter were evaluated
      under gravity and the results obtained were compared with a typical gravity slow
      sand filter (GSSF). All ceramic filters showed significant filtration rates of
      about 50-180 m/h, which is comparatively higher than the typical GSSF. Further,
      purification efficiency of clay-based ceramic filters was evaluated by
      considering important drinking water parameters and contaminants. A significant
      removal potential was achieved by the clay-based ceramic filter with 25% and 30%
      activated carbon along with active agents. Desired drinking water quality
      parameters were achieved by potential removal of nitrite (98.5%), nitrate
      (80.5%), total dissolved solids (62%), total hardness (55%), total organic
      pollutants (89%), and pathogenic microorganisms (100%) using ceramic filters
      within a short duration. The remarkable purification and disinfection
      efficiencies were attributed to the extensive porosity (0.202 cm3 g-1), surface
      area (124.61 m2 g-1), stability, and presence of active nanoparticles such as Cu,
      TiO2, and Ag within the porous matrix of the ceramic filter.

PMID- 29347886
TI  - The Role of Place Cues in Voluntary Stream Segregation for Cochlear Implant
      Users.
AB  - Sequential stream segregation by cochlear implant (CI) listeners was investigated
      using a temporal delay detection task composed of a sequence of regularly
      presented bursts of pulses on a single electrode (B) interleaved with an
      irregular sequence (A) presented on a different electrode. In half of the trials,
      a delay was added to the last burst of the regular B sequence, and the listeners
      were asked to detect this delay. As a jitter was added to the period between
      consecutive A bursts, time judgments between the A and B sequences provided an
      unreliable cue to perform the task. Thus, the segregation of the A and B
      sequences should improve performance. In Experiment 1, the electrode separation
      and the sequence duration were varied to clarify whether place cues help CI
      listeners to voluntarily segregate sounds and whether a two-stream percept needs
      time to build up. Results suggested that place cues can facilitate the
      segregation of sequential sounds if enough time is provided to build up a two
      stream percept. In Experiment 2, the duration of the sequence was fixed, and only
      the electrode separation was varied to estimate the fission boundary. Most
      listeners were able to segregate the sounds for separations of three or more
      electrodes, and some listeners could segregate sounds coming from adjacent
      electrodes.

PMID- 29347874
TI  - Adjunctive Glucocorticoid Therapy in Patients with Septic Shock.
AB  - BACKGROUND: Whether hydrocortisone reduces mortality among patients with septic
      shock is unclear. METHODS: We randomly assigned patients with septic shock who
      were undergoing mechanical ventilation to receive hydrocortisone (at a dose of
      200 mg per day) or placebo for 7 days or until death or discharge from the
      intensive care unit (ICU), whichever came first. The primary outcome was death
      from any cause at 90 days. RESULTS: From March 2013 through April 2017, a total
      of 3800 patients underwent randomization. Status with respect to the primary
      outcome was ascertained in 3658 patients (1832 of whom had been assigned to the
      hydrocortisone group and 1826 to the placebo group). At 90 days, 511 patients
      (27.9%) in the hydrocortisone group and 526 (28.8%) in the placebo group had died
      (odds ratio, 0.95; 95% confidence interval [CI], 0.82 to 1.10; P=0.50). The
      effect of the trial regimen was similar in six prespecified subgroups. Patients
      who had been assigned to receive hydrocortisone had faster resolution of shock
      than those assigned to the placebo group (median duration, 3 days [interquartile
      range, 2 to 5] vs. 4 days [interquartile range, 2 to 9]; hazard ratio, 1.32; 95%
      CI, 1.23 to 1.41; P<0.001). Patients in the hydrocortisone group had a shorter
      duration of the initial episode of mechanical ventilation than those in the
      placebo group (median, 6 days [interquartile range, 3 to 18] vs. 7 days
      [interquartile range, 3 to 24]; hazard ratio, 1.13; 95% CI, 1.05 to 1.22;
      P<0.001), but taking into account episodes of recurrence of ventilation, there
      were no significant differences in the number of days alive and free from
      mechanical ventilation. Fewer patients in the hydrocortisone group than in the
      placebo group received a blood transfusion (37.0% vs. 41.7%; odds ratio, 0.82;
      95% CI, 0.72 to 0.94; P=0.004). There were no significant between-group
      differences with respect to mortality at 28 days, the rate of recurrence of
      shock, the number of days alive and out of the ICU, the number of days alive and
      out of the hospital, the recurrence of mechanical ventilation, the rate of renal
      replacement therapy, and the incidence of new-onset bacteremia or fungemia.
      CONCLUSIONS: Among patients with septic shock undergoing mechanical ventilation,
      a continuous infusion of hydrocortisone did not result in lower 90-day mortality
      than placebo. (Funded by the National Health and Medical Research Council of
      Australia and others; ADRENAL ClinicalTrials.gov number, NCT01448109 .).

PMID- 29347887
TI  - Cryo-Assisted Resection En Bloc, and Cryoablation In Situ, of Primary Breast
      Cancer Coupled With Intraoperative Ultrasound-Guided Tracer Injection: A
      Preliminary Clinical Study.
AB  - The aim of the study was to perform cryosurgery on a primary breast tumor,
      coupled with simultaneous peritumoral and intratumoral tracer injection of a blue
      dye, to evaluate lymphatic mapping. We explored the ability of our strategy to
      prevent tumor cells, but not that of injected tracers, to migrate to the
      lymphovascular drainage during conventional resection of frozen breast
      malignancies. Seventeen patients aged 51 (14) years (mean [standard deviation]),
      presenting primary breast cancer with stage I to IV, were randomly selected and
      treated in The Rudolfinerhaus Private Clinic in Vienna, Austria, and included in
      this preliminary clinical study. Under intraoperative ultrasound, 14 patients
      underwent curative cryo-assisted tumor resection en bloc, coupled with
      peritumoral tracer injection, which consisted of complete tumor freezing and
      concomitant peritumor injection with a blue dye, before resection and sentinel
      lymph node dissection (group A). Group B consists of 3 patients previously
      refused any standard therapy and had palliative tumor cryoablation in situ
      combined with intratumoral tracer injection. The intraoperative ultrasound
      facilitated needle positioning and dye injection timing. In group A, the frozen
      site extruded the dye that was distributed through the unfrozen tumor, the breast
      tissue, and the resection cavity for 12 patients. One to 4 lymph nodes were
      stained for 10 of 14 patients. The resection margin was evaluable. Our
      intraoperative ultrasound-guided performance revealed the injection and migration
      of a blue dye during the frozen resection en bloc and cryoablation in situ of
      primary breast tumors. Sentinel lymph node mapping, pathological determination of
      the tumor, and resection margins were achievable. The study paves the way for
      intraoperative cryo-assisted therapeutic strategies for breast cancer.

PMID- 29347888
TI  - Patient baseline interpersonal problems as moderators of outcome in two
      psychotherapies for bulimia nervosa.
AB  - OBJECTIVE: We tested an aptitude by treatment interaction; namely, whether
      patients' baseline interpersonal problems moderated the comparative efficacy of
      cognitive-behavioral therapy (CBT) vs. interpersonal psychotherapy (IPT) for
      bulimia nervosa (BN). METHOD: Data derived from a randomized-controlled trial.
      Patients reported on their interpersonal problems at baseline; purge frequency at
      baseline, midtreatment, and posttreatment; and global eating disorder severity at
      baseline and posttreatment. We estimated the rate of change in purge frequency
      across therapy, and the likelihood of attaining clinically meaningful improvement
      (recovery) in global eating disorder severity by posttreatment. We then tested
      the interpersonal problem by treatment interactions as predictors of both
      outcomes. RESULTS: Patients with more baseline overly communal/friendly problems
      showed steeper reduction in likelihood of purging when treated with CBT vs. IPT.
      Patients with more problems of being under communal/cold had similar reductions
      in likelihood of purging across both treatments. Patients with more baseline
      problems of being overly agentic were more likely to recover when treated with
      IPT vs. CBT, whereas patients with more problems of being under agentic were more
      likely to recover when treated with CBT vs. IPT. CONCLUSIONS: Interpersonal
      problems related to communion and agency may inform treatment fit among two
      empirically supported therapies for BN.

PMID- 29347889
TI  - Allostery in Orai1 binding to calmodulin revealed from conformational
      thermodynamics.
AB  - Here, we study microscopic mechanism of complex formation between Ca2+-bound
      calmodulin (holoCaM) and Orai1 that regulates Ca2+-dependent inactivation process
      in eukaryotic cells. We compute conformational thermodynamic changes in holoCaM
      with respect to complex of Orai1 bound to C-terminal domain of holoCaM using
      histograms of dihedral angles of the proteins over trajectories from molecular
      dynamics simulations. Our analysis shows that the N-terminal domain residues L4,
      T5, Q41, N42, T44 and E67 of holoCaM get destabilized and disordered due to Orai1
      binding to C-terminal domain of calmodulin affect the N-terminal domain residues.
      Among these residues, polar T44, having maximum destabilization and disorder via
      backbone fluctuations, shows the largest change in solvent exposure. This
      suggests that N-terminal domain is allosterically regulated via T44 by the
      binding of Orai1 to the C-terminal domain.

PMID- 29347890
TI  - Disproportionately higher unintentional injury mortality among Alaska Native
      people, 2006-2015.
AB  - We compared rates of unintentional injury (UI) deaths (total and by injury
      category) among Alaska Native (AN) people to rates of U.S. White (USW) and Alaska
      White (AKW) populations during 2006-2015. The mortality data for AN and AKW
      populations were obtained from Alaska Bureau of Vital Statistics and USW
      mortality data were obtained from WISQARS, the Center for Disease Control and
      Prevention online injury data program. AN and AKW rates were age-adjusted to the
      U.S. 2000 Standard Population and rate ratios (RR) were calculated. AN people had
      higher age-adjusted total UI mortality than the USW (RR = 2.6) and AKW (RR = 2.3)
      populations. Poisoning was the leading cause of UI death among AN people (35.9
      per 100,000), more than twice that of USW (RR = 2.9) and AKW (RR = 2.5). Even
      greater disparities were found between AN people and USW for: natural environment
      (RR = 20.7), transport-other land (RR = 12.4), and drowning/submersion (RR =
      9.1). Rates of AN UI were markedly higher than rates for either USW or AKW.
      Identifying all the ways in which alcohol/drugs contribute to UI deaths would aid
      in prevention efforts. All transportation deaths should be integrated into one
      fatality rate to provide more consistent comparisons between groups.

PMID- 29347891
TI  - Changing character: A narrative review of personality change in psychotherapies
      for personality disorder.
AB  - OBJECTIVE: Personality disorder (PD) is a negative prognostic indicator for
      treatment, and absolute improvements in functioning among these patients are
      often modest. This may be because personality features that give rise to
      dysfunction in PD are not targeted optimally during most treatments. METHOD:
      Attachment, mentalization, core beliefs, and personality organization/defense use
      were identified as personality constructs that have been pursued in treatment
      studies and that are proposed to underlie PD. RESULTS: All constructs correlate
      with psychiatric symptoms, PD diagnosis, and functioning. Defense mechanisms and
      core beliefs further distinguish specific PDs, whereas personality organization
      separates more versus less severe PDs. Evidence from treatment and naturalistic
      studies indicate that maturation of defense mechanisms temporally precedes
      improvements in symptoms and functioning. Changes in attachment and mentalization
      correlate with some outcomes, but mediation of improvement has not been
      established. In psychodynamic therapy, transference interpretations may promote
      amelioration of personality dysfunction. With the exception of attachment, the
      experimental literature is lacking that could explicate the mechanisms by which
      these personality constructs maintain psychosocial dysfunction. CONCLUSIONS:
      Future research should aim to identify changes in these mechanisms that mediate
      positive outcomes in PD, as well as the specific therapeutic procedures that best
      promote positive change in PD.

PMID- 29347892
TI  - Pilot study on the use of data mining to identify cochlear implant candidates.
AB  - OBJECTIVES: The goal of this pilot study was to determine the clinical utility of
      data-mining software that screens for cochlear implant (CI) candidacy. METHODS:
      The Auditory Implant Initiative developed a software module that screens for CI
      candidates via integration with a software system (Noah 4) that serves as a
      depository for hearing test data. To identify candidates, patient audiograms from
      one practice were exported into the screening module. Candidates were tracked to
      determine if any eventually underwent implantation. RESULTS: After loading 4836
      audiograms from the Noah 4 system, the screening module identified 558 potential
      CI candidates. After reviewing the data for the potential candidates, 117 were
      targeted and invited to an educational event. Following the event, a total of six
      candidates were evaluated, and two were implanted. DISCUSSION: This objective
      approach to identifying candidates has the potential to address the gross
      underutilization of CIs by removing any bias or lack of knowledge regarding the
      management of severe to profound sensorineural hearing loss with CIs. CONCLUSION:
      The screening module was an effective tool for identifying potential CI
      candidates at one ENT practice. On a larger scale, the screening module has the
      potential to impact thousands of CI candidates worldwide.

PMID- 29347893
TI  - ["How Beautiful Must I be?"- Physical Attractiveness and Mental Health in
      Adolescents].
AB  - "How Beautiful Must I be?"- Physical Attractiveness and Mental Health in
      Adolescents Physical attractiveness is a high priority for young people. The
      beauty ideals and presentations spread in the media often reinforce self-doubt
      and self-insecurity. In 730 adolescents (age 13 to 20 years) it was measured, how
      they experience appearance-related social pressure (FASD), the extent to which
      physical deficits are perceived (BDDQ), and how these features are related to
      mental symptoms (SDQ). The results demonstrate that young people are very
      concerned about their appearance (30.7 %) and are overly concerned with perceived
      physical defects (29.5 %). In addition, there is a strong appearance-related
      social pressure through peers and parents. The young people particularly affected
      in these areas report more emotional and behavioral problems. The results suggest
      that attention should be given to physical self-assessment as an important factor
      in diagnosis and therapy.

PMID- 29347894
TI  - [Gender-specific Differences in the Degree of Burden on Children and Adolescents
      Taken into Custody].
AB  - Gender-specific Differences in the Degree of Burden on Children and Adolescents
      Taken into Custody Children and adolescents who were taken into care are a high
      risk group for mental disorders such as externalizing problems or conduct
      disorders. 95 children and adolescents who were taken into care were tested with
      the Screening Child Trauma Questionnaire (CTQ) and the Massachusetts Youth
      Screening Instrument 2 (MAYSI-2). In a large proportion of those children and
      adolescents emotional and physical neglect and abuse was identified. There were
      sex differences in suicidal thoughts, somatoform disorders, and emotional abuse.
      The knowledge of mental disorders as well as the gender-specific characteristics
      is important for specialists of inhospital institutions, in order to optimize
      their quality of care.

PMID- 29347895
TI  - [Childhood Experiences of Adolescents in Boarding Schools. A Comparison with
      Adolescents in Residential Care and with the General Population].
AB  - Childhood Experiences of Adolescents in Boarding Schools. A Comparison with
      Adolescents in Residential Care and with the General Population Various studies
      indicate that students in boarding schools experience a lot of violence during
      their accommodation. However, it is not proved whether adolescents in boarding
      schools are also a burdensome group regarding early childhood experiences such as
      neglect and abuse. The aim of the study was to find out more about the
      experiences of adolescents in boarding schools and to determine whether there are
      differences between adolescents in residential care and between the general
      population. Furthermore, it should be examined whether boys and girls differ in
      their experiences. In the study, adolescents of boarding schools and of
      residential care all over Germany, starting at the age of 15 (n = 322), were
      asked regarding physical and emotional neglect/abuse, light/severe parent
      violence, negative/positive educational behavior of the parents. The results show
      that students in boarding schools were less likely to be affected by childhood
      maltreatment and more likely to have experienced positive parental behavior
      compared to children in residential care. Compared to the general population,
      students in boarding schools were more often and more severely affected by
      parental violence. Moreover, girls had experienced parental violence more often
      than boys. The results indicate that in boarding schools there is a need for
      support offers for adolescents with a history of violent experiences and that the
      risk group should be identified directly at the admission to the school.

PMID- 29347896
TI  - [Impact of Different Types of Fathers on Family Climate in Young Adulthood: A
      Multi-perspective Longitudinal Study on 14 to 27 Year Olds and their Fathers].
AB  - Impact of Different Types of Fathers on Family Climate in Young Adulthood: A
      Multi-perspective Longitudinal Study on 14 to 27 Year Olds and their Fathers In a
      13 year longitudinal study, the influence of three types of fathers on the family
      climate was analyzed. In a sample of 213 subjects, their 169 fathers and their
      210 mothers, the family environment ( Family Environment Scales) was examined
      when the subjects were young adults (M = 26.89, SD = 1.32). The results of the
      study point to significant changes in family climate in those young adults who
      described their father as increasingly negative (N = 28) or distant (N = 11) when
      in adolescence. These two groups showed a more negative family environment and
      greater differences between the perspectives of fathers and their young adult
      children than the group of young adults who described their father as normative
      (N = 174) when in adolescence. The highest discrepancies were described by young
      adults with a negative relationship with their father in adolescence. The
      findings show a long lasting importance of father-child interactions in
      adolescence.

PMID- 29347898
TI  - ?

PMID- 29347897
TI  - [Effects of Bilingualism on Cognitive Functions in Early Childhood].
AB  - Effects of Bilingualism on Cognitive Functions in Early Childhood Studies have
      revealed advantages in cognitive functions among children with bilingualism. In
      this study we investigate cognitive functions in monolingual and bilingual
      preschool children taking socioeconomic status into account. The study population
      consists of 40 monolingual (German) children (Mage = 5.0 +/- 0.4) and 23
      bilingual (German/English) children (Mage = 5.1 +/- 0.6). A neuropsychological
      test battery was conducted. The analyses revealed better performance for
      bilingual children. However, significant group differences were only found with
      respect to phonological short-term memory. Controlling for socioeconomic status,
      intelligence and balanced bilingualism, only slight advantages in cognitive
      performance were found for bilingual children. Due to high socioeconomic status
      in both groups, we suppose a ceiling effect. Children's development might be
      extensively promoted in upper class families and therefore bilingualism may not
      have additional impact on cognitive functions in these children.

PMID- 29347899
TI  - [Congress Dates].

PMID- 29347900
TI  - [Authors].

PMID- 29347901
TI  - [Test Reviews].

PMID- 29347903
TI  - Child, Caregiver, and Health Care Provider Perspectives and Experiences Regarding
      Disclosure of HIV Status to Perinatally Infected Children in Lima, Peru.
AB  - BACKGROUND: Despite recommendations for disclosure of HIV status to children
      living with HIV (CLHIV), fewer than half of CLHIV at the Instituto Nacional de
      Salud del Nino (INSN) in Lima, Peru, have had disclosure. How and when the
      disclosure process for CLHIV should take place in Peru has not been studied.
      METHODS: We conducted a qualitative study at INSN to explore perceptions and
      experiences of 6 health care providers (HCPs), 14 disclosed and nondisclosed
      CLHIV (8-17 years), and their 14 caregivers regarding knowledge of illness,
      disclosure of HIV status, and appropriate disclosure approaches. RESULTS:
      Disclosed children wanted to be told their diagnosis earlier. Nondisclosed
      children expressed frustration taking medications. Caregivers and HCPs discussed
      motivations to disclose, including educating, honesty, improving medication
      adherence, and preventing secondary transmission. CONCLUSION: Culturally
      appropriate guidelines and training for HCPs and caregivers are needed to support
      disclosure of children's HIV status and ongoing support for CLHIV.

PMID- 29347904
TI  - Social skills training and play group intervention for children with oppositional
      defiant disorders/conduct disorder: Mediating mechanisms in a head-to-head
      comparison.
AB  - OBJECTIVE: Social-cognitive information processing, social skills, and social
      interactions are problem-maintaining variables for aggressive behavior in
      children. We hypothesized that these factors may be possible mediators of the
      mechanism of change in the child-centered treatment of conduct disorders (CDs).
      The aim of the present study (Clinical trials.gov Identifier: NCT01406067) was to
      examine putative mechanisms of change for the decrease in oppositional-defiant
      behavior resulting from child-centered treatment of patients with oppositional
      defiant disorder (ODD) or CD. METHOD: 91 children (age 6-12 years) with ODD/CD
      were randomized to receive either social skills training or to a resource
      activating play group. Mediator analyses were conducted using path analyses.
      RESULTS: The assumed mediating effects were not significant. However, alternative
      models with the putative mediators and outcome in reversed positions showed
      significant indirect effects of the oppositional-defiant symptoms as mediator for
      the decrease of disturbance of social-information processing, social skills, and
      social interactions. CONCLUSIONS: The proposed model for mechanisms of change
      could not be confirmed, with the results pointing to a reversed causality.
      Variables other than those hypothesized must be responsible for mediating the
      effects of the intervention on child oppositional-defiant behavior. Possible
      mechanisms of change were discussed.

PMID- 29347905
TI  - Synthesize of silver-nanoparticles by plant extract and its application for
      preconcentration of cadmium followed by flame atomic absorption spectrometry.
AB  - In this paper, Mentha pulegium leaves extract was used as a green reducing agent
      for the synthesis of silver-nanoparticles. The synthesized silver-nanoparticles
      were characterized by UV-VIS spectrophotometry, transmission electron microscopy,
      X-ray spectroscopy and used as an adsorbent for preconcentration of trace levels
      of cadmium (II). After the desorption of cadmium (II) in 5 mol L-1 formic acid,
      the desorbent solution was aspirated into the flame atomic absorption
      spectrometry for the determination of cadmium. In order to optimize the
      experimental condition, a response surface methodology based on central composite
      design was used. The optimum conditions are: pH: 8.6, amounts of adsorbent: 30
      mg, 10 min extraction time and desorption time of 2 min. Under the optimum
      condition, the calibration curve was linear in the range of 5-200 MUg L-1 cadmium
      (II) ion with a correlation coefficient of 0.9995. The limit of detection was 1.1
      MUg L-1 and the relative standard deviation for 25 MUg L-1 cadmium (II) ion was
      3.0% (n = 5). In order to check the applicability of the proposed method,
      different real samples were analyzed. Also, the accuracy of this method was
      successfully checked by the analysis of certified reference material and spike
      tests.

PMID- 29347906
TI  - Expression and functional analysis of the Propamocarb-related gene CsDIR16 in
      cucumbers.
AB  - BACKGROUND: Cucumber downy mildew is among the most important diseases that can
      disrupt cucumber production. Propamocarb, also known as propyl-[3
      (dimethylamino)propyl]carbamate (PM), is a systemic carbamate fungicide pesticide
      that is widely applied in agricultural production because of its high efficiency
      of pathogens control, especially cucumber downy mildew. However, residual PM can
      remain in cucumbers after the disease has been controlled. To explore the
      molecular mechanisms of PM retention, cucumber cultivars 'D9320' (with the
      highest residual PM content) and 'D0351' (lowest residual PM content) were
      studied. High-throughput tag-sequencing (Tag-Seq) results showed that the CsDIR16
      gene was related to PM residue, which was verified using transgenic technology.
      RESULTS: We investigated the activity of a dirigent cucumber protein encoded by
      the CsDIR16 in gene response to stress induced by PM treatment. Gene-expression
      levels of CsDIR16 were up-regulated in the fruits, leaves, and stems of 'D0351'
      plants in response to PM treatment. However, in cultivar 'D9320', CsDIR16 levels
      were down-regulated in the leaves and stems after PM treatment, with no
      statistically significant differences observed in the fruits. Induction by
      jasmonic acid, abscisic acid, polyethylene glycol 4000, NaCl, and Corynespora
      cassiicola Wei (Cor) resulted in CsDIR16 up-regulation in 'D0351' and 'D9320'.
      Expression after salicylic acid treatment was up-regulated in 'D0351', but was
      down-regulated in 'D9320'. CsDIR16 overexpression lowered PM residues, and these
      were more rapidly reduced in CsDIR16(+) transgenic 'D9320' plants than in wild
      type 'D9320' and CsDIR16(-) transgenic plants. CONCLUSIONS: Analyses of the
      CsDIR16-expression patterns in the cucumber cultivars with the highest and lowest
      levels of PM residue, and transgenic validation indicated that CsDIR16 plays a
      positive role in reducing PM residues. The findings of this study help understand
      the regulatory mechanisms occurring in response to PM stress in cucumbers and in
      establishing the genetic basis for developing low-pesticide residue cucumber
      cultivars.

PMID- 29347907
TI  - Blood lactate is a predictor of short-term mortality in patients with myocardial
      infarction complicated by heart failure but without cardiogenic shock.
AB  - BACKGROUND: Mortality in patients with acute myocardial infarction (AMI) has
      improved substantially with modern therapy including percutaneous coronary
      interventions (PCI) but remains high in certain subgroups such as patients
      presenting with overt cardiogenic shock. However, the risk for AMI in patients
      presenting acutely with signs of heart failure but without cardiogenic shock is
      less well described. We aimed to identify risk factors for mortality in AMI
      patients with heart failure without overt cardiogenic shock. METHODS: Using data
      from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR), we
      identified patients with operator-registered heart failure (Killip class II-IV),
      and evaluated predictors of mortality based on clinical factors from review of
      patient records. RESULTS: A total of 1260 unique patients with acute myocardial
      infarction underwent PCI in 2014, of which 77 patients (7%) showed signs of heart
      failure (Killip II-IV) Overall 30-day mortality in patients with Killip class II
      IV was 20% (N = 15). In patients classified Killip IV (1%), 30-day mortality was
      50% (N = 6). In patients presenting with mild to moderate heart failure (Killlip
      class II-III), 30-day mortality was 14% (N = 9). In patients with Killip class II
      III, lactate >=2.5 mmol/L was associated with 30-day mortality, whereas systolic
      blood pressure < 90 mmHg, age, sex and BMI were not. In patients with lactate <
      2.5 mmol/L 30-day mortality was 5% (N = 2) whereas mortality was 28% (N = 7) with
      lactate >=2.5 mmol/L. This cut-off provided discriminative information on 30-day
      mortality (area under ROC curve 0.74). CONCLUSIONS: In patients with AMI and
      signs of mild to moderate heart failure, lactate >=2.5 mmol/L provides additional
      prognostic information. Interventions to reduce risk may be targeted to these
      patients.

PMID- 29347908
TI  - Management and outcomes of patients presenting with sepsis and septic shock to
      the emergency department during nursing handover: a retrospective cohort study.
AB  - BACKGROUND: Clinical handover is an important process for the transition of
      patient-care responsibility to the next healthcare provider, but it may divert
      the attention of the team away from active patients. This is challenging in the
      Emergency Department (ED) because of highly dynamic patient conditions and is
      likely relevant in conditions that requires time-sensitive therapies, such as
      sepsis. We aimed to examine the management and outcomes of patients presenting
      with sepsis and septic shock to the ED during nursing handover. METHODS: This
      retrospective cohort study was conducted at a 115-bed ED and more than 200,000
      annual ED visits, within a 900-bed academic tertiary care center. Data on
      Surviving Sepsis Campaign (SSC) bundle elements and hospital mortality were
      collected for all >=14-year-old patients who presented to the ED with a diagnosis
      of sepsis and septic shock between January 1, 2011 and October 30, 2013. Our
      primary outcome was time to antibiotics, were other SSC bundle elements and
      mortality counted as secondary outcomes. Patients were divided into two groups:
      1) handover time group, comprising patients who presented an hour before or after
      the start of handover time (6-8 AM/PM), and 2) non-handover time group,
      comprising patients who presented over the remaining 20 h. RESULTS: During the
      study period, 1330 patients presented with sepsis or septic shock (228, handover
      time group; 1102, non-handover time group). No significant differences were found
      between the handover time and non-handover time groups, respectively, in median
      time to antibiotic administration (100 [interquartile range (IQR) 57-172] vs. 95
      [IQR 50-190] minutes; P = 0.07), median time to serum lactate result (162 [IQR
      108-246] vs. 156 [IQR 180-246] minutes; P = 0.33) and median time to obtain blood
      culture (54 [IQR 36-119] vs. 52 [IQR 28-103] minutes; P = 0.52), and hospital
      mortality rate (29.4% vs. 28.9%; P = 0.89). CONCLUSION: No significant
      differences were found in median time of SSC bundle elements or hospital
      mortality between patients who presented during the handover and non-handover
      times.

PMID- 29347910
TI  - Getting messier with TIDieR: embracing context and complexity in intervention
      reporting.
AB  - BACKGROUND: The Template for Intervention Description and Replication (TIDieR)
      checklist and guide was developed by an international team of experts to promote
      full and accurate description of trial interventions. It is now widely used in
      health research. The aim of this paper is to describe the experience of using
      TIDieR outside of trials, in a range of applied health research contexts, and
      make recommendations on its usefulness in such settings. MAIN BODY: We used the
      TIDieR template for intervention description in six applied health research
      projects. The six cases comprise a diverse sample in terms of clinical problems,
      population, settings, stage of intervention development and whether the
      intervention was led by researchers or the service deliverers. There was also
      variation in how the TIDieR description was produced in terms of contributors and
      time point in the project. Researchers involved in the six cases met in two
      workshops to identify issues and themes arising from their experience of using
      TIDieR. We identified four themes which capture the difficulties or complexities
      of using TIDieR in applied health research: (i) fidelity and adaptation: all
      aspects of an intervention can change over time; (ii) voice: the importance of
      clarity on whose voice the TIDieR description represents; (iii) communication
      beyond the immediate context: the usefulness of TIDieR for wider dissemination
      and sharing; (iv) the use of TIDieR as a research tool. CONCLUSION: We found
      TIDieR to be a useful tool for applied research outside the context of clinical
      trials and we suggest four revisions or additions to the original TIDieR which
      would enable it to better capture these complexities in applied health research:
      An additional item, 'voice' conveys who was involved in preparing the TIDieR
      template, such as researchers, service users or service deliverers. An additional
      item, 'stage of implementation' conveys what stage the intervention has reached,
      using a continuum of implementation research suggested by the World Health
      Organisation. A new column, 'modification' reminds authors to describe
      modifications to any item in the checklist. An extension of the 'how well' item
      encourages researchers to describe how contextual factors affected intervention
      delivery.

PMID- 29347909
TI  - Identification of minor effect QTLs for plant architecture related traits using
      super high density genotyping and large recombinant inbred population in maize
      (Zea mays).
AB  - BACKGROUND: Plant Architecture Related Traits (PATs) are of great importance for
      maize breeding, and mainly controlled by minor effect quantitative trait loci
      (QTLs). However, cloning or even fine-mapping of minor effect QTLs is very
      difficult in maize. Theoretically, large population and high density genetic map
      can be helpful for increasing QTL mapping resolution and accuracy, but such a
      possibility have not been actually tested. RESULTS: Here, we employed a
      genotyping-by-sequencing (GBS) strategy to construct a linkage map with 16,769
      marker bins for 1021 recombinant inbred lines (RILs). Accurately mapping of well
      studied genes P1, pl1 and r1 underlying silk color demonstrated the map quality.
      After QTL analysis, a total of 51 loci were mapped for six PATs. Although all of
      them belong to minor effect alleles, the lengths of the QTL intervals, with a
      minimum and median of 1.03 and 3.40 Mb respectively, were remarkably reduced as
      compared with previous reports using smaller size of population or small number
      of markers. Several genes with known function in maize were shown to be
      overlapping with or close neighboring to these QTL peaks, including na1, td1, d3
      for plant height, ra1 for tassel branch number, and zfl2 for tassel length. To
      further confirm our mapping results, a plant height QTL, qPH1a, was verified by
      an introgression lines (ILs). CONCLUSIONS: We demonstrated a method for high
      resolution mapping of minor effect QTLs in maize, and the resulted comprehensive
      QTLs for PATs are valuable for maize molecular breeding in the future.

PMID- 29347911
TI  - microRNAs associated with early neural crest development in Xenopus laevis.
AB  - BACKGROUND: The neural crest (NC) is a class of transitory stem cell-like cells
      unique to vertebrate embryos. NC cells arise within the dorsal neural tube where
      they undergo an epithelial to mesenchymal transition in order to migrate and
      differentiate throughout the developing embryo. The derivative cell types give
      rise to multiple tissues, including the craniofacial skeleton, peripheral nervous
      system and skin pigment cells. Several well-studied gene regulatory networks
      underpin NC development, which when disrupted can lead to various
      neurocristopathies such as craniofrontonasal dysplasia, DiGeorge syndrome and
      some forms of cancer. Small RNAs, such as microRNAs (miRNAs) are non-coding RNA
      molecules important in post-transcriptional gene silencing and critical for
      cellular regulation of gene expression. RESULTS: To uncover novel small RNAs in
      NC development we used high definition adapters and next generation sequencing of
      libraries derived from ectodermal explants of Xenopus laevis embryos induced to
      form neural and NC tissue. Ectodermal and blastula animal pole (blastula) stage
      tissues were also sequenced. We show that miR-427 is highly abundant in all four
      tissue types though in an isoform specific manner and we define a set of 11
      miRNAs that are enriched in the NC. In addition, we show miR-301a and miR-338 are
      highly expressed in both the NC and blastula suggesting a role for these miRNAs
      in maintaining the stem cell-like phenotype of NC cells. CONCLUSION: We have
      characterised the miRNAs expressed in Xenopus embryonic explants treated to form
      ectoderm, neural or NC tissue. This has identified novel tissue specific miRNAs
      and highlighted differential expression of miR-427 isoforms.

PMID- 29347913
TI  - An unusual case of infective pneumocephalus: case report of pneumocephalus
      exacerbated by continuous positive airway pressure.
AB  - BACKGROUND: Pneumocephalus, illustrated by air in the cranial vault is relatively
      infrequent and generally associated with neurosurgery, trauma, meningitis and
      barotrauma. However cases of spontaneous non-traumatic pneumocephalus remain
      rare. While the relationship between continuous positive airway pressure (CPAP)
      and atraumatic pneumocephalus has been previously reported, to our knowledge the
      rare presentation associated with sinus wall osteomyelitis has never been
      described. We summarize here the case of a 67-year-old woman's acute presentation
      of Streptococcus salvarius infection after a sudden drop in her consciousness.
      CASE PRESENTATION: The patient was brought to hospital by family reporting a one
      week history of sudden deterioration, cognitive decline, and lethargy. The
      patient presented with reduced arousal, cognitive function (Glasgow Coma Scale:
      10, Abbreviated Mental Test Score:CS, 0 AMTS), and no history of trauma. Computed
      Tomography (CT) imaging was ordered and identified a significant pneumocephalus
      with no cranial defect. Further investigations acknowledged possible sinus or
      middle ear disease, which was highlighted by the discovery of S. salivarius by
      polymerase chain reaction (PCR) and potentially exacerbated by the use of
      nocturnal continuous positive airway pressure (CPAP). The patient made a complete
      recovery by eliminating likely causative factors and long term regimental
      antibiotics administration. CONCLUSION: This case highlights a rare neurological
      presentation of S. salivarius infection with a mixed aetiology of spontaneous
      pneumocephalus. This case features an atypical complication associated with CPAP
      use, and to our knowledge is the first case to be associated with sinus wall
      osteomyelitis. Recognition of the clinical features and risk factors for
      spontaneous pneumocephalus -while rare-serve to broaden our clinical index of
      suspicion when presented with patients experiencing neurological deficit.
      Information from this case may also aid in improving prevention, early diagnosis,
      and future management.

PMID- 29347912
TI  - Genome-wide analysis of the potato Hsp20 gene family: identification, genomic
      organization and expression profiles in response to heat stress.
AB  - BACKGROUND: Heat shock proteins (Hsps) are essential components in plant
      tolerance mechanism under various abiotic stresses. Hsp20 is the major family of
      heat shock proteins, but little of Hsp20 family is known in potato (Solanum
      tuberosum), which is an important vegetable crop that is thermosensitive.
      RESULTS: To reveal the mechanisms of potato Hsp20s coping with abiotic stresses,
      analyses of the potato Hsp20 gene family were conducted using bioinformatics
      based methods. In total, 48 putative potato Hsp20 genes (StHsp20s) were
      identified and named according to their chromosomal locations. A sequence
      analysis revealed that most StHsp20 genes (89.6%) possessed no, or only one,
      intron. A phylogenetic analysis indicated that all of the StHsp20 genes, except
      10, were grouped into 12 subfamilies. The 48 StHsp20 genes were randomly
      distributed on 12 chromosomes. Nineteen tandem duplicated StHsp20s and one pair
      of segmental duplicated genes (StHsp20-15 and StHsp20-48) were identified. A cis
      element analysis inferred that StHsp20s, except for StHsp20-41, possessed at
      least one stress response cis-element. A heatmap of the StHsp20 gene family
      showed that the genes, except for StHsp20-2 and StHsp20-45, were expressed in
      various tissues and organs. Real-time quantitative PCR was used to detect the
      expression level of StHsp20 genes and demonstrated that the genes responded to
      multiple abiotic stresses, such as heat, salt or drought stress. The relative
      expression levels of 14 StHsp20 genes (StHsp20-4, 6, 7, 9, 20, 21, 33, 34, 35,
      37, 41, 43, 44 and 46) were significantly up-regulated (more than 100-fold) under
      heat stress. CONCLUSIONS: These results provide valuable information for
      clarifying the evolutionary relationship of the StHsp20 family and in aiding
      functional characterization of StHsp20 genes in further research.

PMID- 29347914
TI  - In-depth proteomic analysis of boar spermatozoa through shotgun and gel-based
      methods.
AB  - BACKGROUND: Mature spermatozoa contain numerous epididymal and seminal plasma
      proteins, which full identification through high-throughput technologies may
      allow for a better understanding of the sperm biology. Therefore, we conducted a
      global proteomic analysis of boar spermatozoa through shotgun and gel-based
      methodologies. RESULTS: The total proteins were extracted from mature spermatozoa
      and subjecsted to proteome analyses. Functional analyses of gene ontology
      representations and pathway enrichments were conducted on the shotgun dataset,
      followed by immunology and gene expression validations. Shotgun and gel-based
      approaches allowed the detection of 2728 proteins and 2123 spots, respectively.
      Approximately 38% and 59% of total proteins were respectively fully and partially
      annotated, and 3% were unknown. Gene ontology analysis indicated high proportions
      of proteins associated with intracellular and cytoplasm localizations, protein
      and nucleic acid binding, hydrolase and transferase activities, and cellular,
      metabolic, and regulation of biological processes. Proteins associated with
      phosphorylation processes and mitochondrial membranes, nucleic acid binding, and
      phosphate and phosphorous metabolics represented 77% of the dataset. Pathways
      associated with oxidative phosphorylation, citrate cycle, and extra-cellular
      matrix-receptor interaction were significantly enriched. Protein complex,
      intracellular organelle, cytoskeletal parts, fertilization and reproduction, and
      gap junction pathway were significantly enriched within the top 116 highly
      abundant proteins. Nine randomly selected protein candidates were confirmed with
      gel-based identification, immunofluorescence detection, and mRNA expression.
      CONCLUSIONS: This study offers an in-depth proteomic mapping of mature boar
      spermatozoa that will enable comparative and discovery research for the
      improvement of male fertility.

PMID- 29347915
TI  - The role of hypoglycemia in the burden of living with diabetes among adults with
      diabetes and family members: results from the DAWN2 study in The Netherlands.
AB  - BACKGROUND: To examine the relation between self-reported hypoglycemic events,
      worries about these episodes, and the burden of diabetes in adults with diabetes
      and family members from The Netherlands. METHODS: As part of the second
      multinational Diabetes Attitudes, Wishes and Needs (DAWN2) study, 412 Dutch
      adults with type 1 or type 2 diabetes and 86 family members completed questions
      about the burden of living with diabetes, the frequency of hypoglycemia, worries
      about these events, and several demographic and clinical factors. Analyses
      included hierarchical logistic regression. RESULTS: In total, 41% of people with
      diabetes and 56% of family members considered diabetes at least somewhat of a
      burden. In people with diabetes, diabetes burden was independently associated
      with self-reported current insulin use (fully adjusted OR = 2.75, 95% CI 1.49
      5.10), self-reported frequent non-severe hypoglycemia in the past year (OR =
      2.45, 1.25-4.83), self-reported severe hypoglycemia in the past year (OR = 1.91,
      1.02-3.58), and being very worried about hypoglycemia at least occasionally (OR =
      3.64, 2.18-6.10). For family members, the odds of experiencing living with
      diabetes as a burden was increased only for participants who were at least
      occasionally very worried about hypoglycemia (adjusted OR = 5.07, 1.12-23.00).
      CONCLUSIONS: Approximately half of adults with diabetes and adult family members
      experienced at least some diabetes burden. In both groups, diabetes burden
      appeared to be associated with being very worried about hypoglycemia at least
      occasionally. If these results are replicated, new intervention studies could
      test new ways of decreasing the traumatic consequences of previous or anticipated
      hypoglycemic events for people with diabetes and family members.

PMID- 29347916
TI  - Cost-effectiveness of prostate cancer screening: a systematic review of decision
      analytical models.
AB  - BACKGROUND: There is ongoing debate about the harms and benefits of a national
      prostate cancer screening programme. Several model-based cost-effectiveness
      analyses have been developed to determine whether the benefits of prostate cancer
      screening outweigh the costs and harms caused by over-detection and over
      treatment, and the different approaches may impact results. METHODS: To identify
      models of prostate cancer used to assess the cost-effectiveness of prostate
      cancer screening strategies, a systematic review of articles published since 2006
      was conducted using the NHS Economic Evaluation Database, Medline, EMBASE and HTA
      databases. The NICE website, UK National Screening website, reference lists from
      relevant studies were also searched and experts contacted. Key model features,
      inputs, and cost-effectiveness recommendations were extracted. RESULTS: Ten
      studies were included. Four of the studies identified some screening strategies
      to be potentially cost-effective at a PSA threshold of 3.0 ng/ml, including
      single screen at 55 years, annual or two yearly screens starting at 55 years old,
      and delayed radical treatment. Prostate cancer screening was modelled using both
      individual and cohort level models. Model pathways to reflect cancer progression
      varied widely, Gleason grade was not always considered and clinical verification
      was rarely outlined. Where quality of life was considered, the methods used did
      not follow recommended practice and key issues of overdiagnosis and overtreatment
      were not addressed by all studies. CONCLUSION: The cost-effectiveness of prostate
      cancer screening is unclear. There was no consensus on the optimal model type or
      approach to model prostate cancer progression. Due to limited data availability,
      individual patient-level modelling is unlikely to increase the accuracy of cost
      effectiveness results compared with cohort-level modelling, but is more suitable
      when assessing adaptive screening strategies. Modelling prostate cancer is
      challenging and the justification for the data used and the approach to modelling
      natural disease progression was lacking. Country-specific data are required and
      recommended methods used to incorporate quality of life. Influence of data inputs
      on cost-effectiveness results need to be comprehensively assessed and the model
      structure and assumptions verified by clinical experts.

PMID- 29347917
TI  - Does different information disclosure on placebo control affect blinding and
      trial outcomes? A case study of participant information leaflets of randomized
      placebo-controlled trials of acupuncture.
AB  - BACKGROUND: While full disclosure of information on placebo control in
      participant information leaflets (PILs) in a clinical trial is ethically required
      during informed consent, there have been concerning voices such complete
      disclosures may increase unnecessary nocebo responses, breach double-blind
      designs, and/or affect direction of trial outcomes. Taking an example of
      acupuncture studies, we aimed to examine what participants are told about placebo
      controls in randomized, placebo-controlled trials, and how it may affect blinding
      and trial outcomes. METHODS: Authors of published randomized, placebo-controlled
      trials of acupuncture were identified from PubMed search and invited to provide
      PILs for their trials. The collected PILs were subjected to content analysis and
      categorized based on degree of information disclosure on placebo. Blinding index
      (BI) as a chance-corrected measurement of blinding was calculated and its
      association with different information disclosure was examined. The impact of
      different information disclosure from PILs on primary outcomes was estimated
      using a random effects model. RESULTS: In 65 collected PILs, approximately 57% of
      trials fully informed the participants of placebo control, i.e. full disclosure,
      while the rest gave deceitful or no information on placebo, i.e. no disclosure.
      Placebo groups in the studies with no disclosure tended to make more opposite
      guesses on the type of received intervention than those with disclosure, which
      may reflect wishful thinking (BI -0.21 vs. -0.16; p = 0.38). In outcome analysis,
      studies with no disclosure significantly favored acupuncture than those with full
      disclosure (standardized mean difference - 0.43 vs. -0.12; p = 0.03), probably
      due to enhanced expectations. CONCLUSIONS: How participants are told about
      placebos can be another potential factor that may influence participant blinding
      and study outcomes by possibly modulating patient expectation. As we have few
      empirical findings on this issue, future studies are needed to determine whether
      the present findings are relevant to other medical disciplines and at the same
      time a routine practice of fully disclosing placebo information in PILs calls for
      reevaluation.

PMID- 29347918
TI  - Somatic evolutionary timings of driver mutations.
AB  - BACKGROUND: A unified analysis of DNA sequences from hundreds of tumors concluded
      that the driver mutations primarily occur in the earliest stages of cancer
      formation, with relatively few driver mutation events detected in the late
      arising subclones. However, emerging evidence from the sequencing of multiple
      tumors and tumor regions per individual suggests that late-arising subclones with
      additional driver mutations are underestimated in single-sample analyses.
      METHODS: To test whether driver mutations generally map to early tumor
      development, we examined multi-regional tumor sequencing data from 101
      individuals reported in 11 published studies. Following previous studies, we
      annotated mutations as early-arising when all tumors/regions had those mutations
      (ubiquitous). We then inferred the fraction of mutations occurring early and
      compared it with late-arising mutations that were found in only single
      tumors/regions. RESULTS: While a large fraction of driver mutations in tumors
      occurred relatively early in cancers, later driver mutations occurred at least as
      frequently as the early drivers in a substantial number of patients. This result
      was robust to many different approaches to annotate driver mutations. The
      relative frequency of early and late driver mutations varied among patients of
      the same cancer type and in different cancer types. We found that previous
      reports of the preponderance of early driver mutations were primarily informed by
      analysis of single tumor variant allele profiles, with which it is challenging to
      clearly distinguish between early and late drivers. CONCLUSIONS: The origin and
      preponderance of new driver mutations are not limited to early stages of tumor
      evolution, with different tumors and regions showing distinct driver mutations
      and, consequently, distinct characteristics. Therefore, tumors with extensive
      intratumor heterogeneity appear to have many newly acquired drivers.

PMID- 29347919
TI  - Knowledge, attitudes and practices on Schistosomiasis in sub-Saharan Africa: a
      systematic review.
AB  - BACKGROUND: Schistosomiasis remains a global health problem with an estimated 250
      million people in 78 countries infected, of whom 85% live in Sub-Saharan Africa.
      Preventive chemotherapy remains the key public health strategy to combat
      schistosomiasis worldwide. Recently the WHO emphasized on the use of integrative
      approaches in the control and elimination of schistosomiasis. However, a detailed
      understanding of sociocultural factors that may influence the uptake of the
      intended health activities and services is vital. Thus, our study sought to
      understand the knowledge, attitudes, perceptions, beliefs and practices about
      schistosomiasis in various communities in Sub-Saharan Africa. METHODS: A
      systematic search of literature for the period 2006-2016 was done on Medline,
      PubMed, CINAHL, Psych info and Google Scholar using the following key words
      "Schistosomiasis, S. mansoni, S. haematobium, knowledge, attitudes, perceptions,
      beliefs and practices in Sub-Saharan Africa" in combination with Bolean operators
      (OR, AND). In this context, we reviewed studies conducted among school children,
      community members and caregivers of preschool children. Thematic analysis was
      utilised for the overall synthesis of the selected studies. This was done after
      reading the articles in depth. Themes were identified and examined for
      similarities, differences and contradictions. RESULTS: Gaps in schistosomiasis
      related knowledge and sociocultural barriers towards the uptake of preventive and
      treatment services among communities in Sub-Saharan Africa were identified. In
      addition to limited knowledge and negative attitudes, risky water related
      practices among community members, school children and caregivers of preschool
      children were identified as key factors promoting transmission of the disease.
      CONCLUSION: The study concluded that a comprehensive health education programme
      using contextual and standardised training tools may improve peoples' knowledge,
      attitudes and practices in relation to schistosomiasis prevention and control.
      Findings also highlight the significance of including caregivers in the planning
      and implementation schistosomiasis control programs targeting pre-school
      children.

PMID- 29347920
TI  - A qualitative study of tobacco interventions for LGBTQ+ youth and young adults:
      overarching themes and key learnings.
AB  - BACKGROUND: Smoking prevalence is very high among lesbian, gay, bisexual,
      transgendered and queer (LGBTQ+) youth and young adults (YYA) compared to non
      LGBTQ+ YYA. A knowledge gap exists on culturally appropriate and effective
      prevention and cessation efforts for members of this diverse community, as
      limited interventions have been developed with and for this population, and there
      are very few studies determining the impact of these interventions. This study
      identifies the most salient elements of LGBTQ+ cessation and prevention
      interventions from the perspective of LGBTQ+ YYA. METHODS: Three descriptions of
      interventions tailored for LGBTQ+ YYA (group cessation counselling, social
      marketing, and a mobile phone app with social media incorporated), were shared
      with LGBTQ+ YYA via 24 focus groups with 204 participants in Toronto and Ottawa,
      Canada. Open-ended questions focused on their feelings, likes and dislikes, and
      concerns about the culturally modified intervention descriptions. Framework
      analysis was used to identify overarching themes across all three intervention
      descriptions. RESULTS: The data revealed eight overarching themes across all
      three intervention descriptions. Smoking cessation and prevention interventions
      should have the following key attributes: 1) be LGBTQ+ - specific; 2) be
      accessible in terms of location, time, availability, and cost; 3) be inclusive,
      relatable, and highlight diversity; 4) incorporate LGBTQ+ peer support and
      counselling services; 5) integrate other activities beyond smoking; 6) be
      positive, motivational, uplifting, and empowering; 7) provide concrete coping
      mechanisms; and 8) integrate rewards and incentives. CONCLUSIONS: LGBTQ+ YYA
      focus group participants expressed a desire for an intervention that can
      incorporate these key elements. The mobile phone app and social media campaign
      were noted as potential interventions that could include all the essential
      elements.

PMID- 29347921
TI  - Prospective pre- and post-race evaluation of biochemical, electrophysiologic, and
      echocardiographic indices in 30 racing thoroughbred horses that received
      furosemide.
AB  - BACKGROUND: Exercise induced cardiac fatigue (EICF) and cardiac dysrhythmias are
      well described conditions identified in high-level human athletes that increase
      in frequency with intensity and duration of exercise. Identification of these
      conditions requires an understanding of normal pre- and post-race cardiac
      assessment values. The objectives of this study were to (1) characterize selected
      indices of cardiac function, electrophysiologic parameters, and biochemical
      markers of heart dysfunction prior to and immediately after high level racing in
      Thoroughbred horses receiving furosemide; and (2) create pre- and post-race
      reference values in order to make recommendations on possible screening practices
      for this population in the future. RESULTS: Thirty Thoroughbred horses were
      enrolled in the study with an age range of 3-6 years. All horses received
      furosemide prior to racing. Physical exams, ECGs, and echocardiograms were
      performed prior to racing (T0) and within 30-60 min following the race (T1).
      Blood samples were obtained at T0, T1, 4 h post-race (T4) and 24 h after the race
      (T24). Electrolytes, hematocrit, cardiac troponin I, and partial pressure CO2
      values were obtained at all time points. Heart rate was significantly increased
      post-race compared to baseline value with a median difference of 49 bpm, 95% CI
      [31,58],(P < 0.0001). No dysrhythmias were noted during ECG assessment. Following
      the race, an increase in number of horses demonstrating regurgitation through the
      aorta and AV valves was noted. Systolic function measured by fractional
      shortening increased significantly with a mean difference of 7.9%, 95% CI [4.8,
      10.9], (P < 0.0001). Cardiac troponin I was not different at pre- and immediately
      post-race time points, but was significantly increased at T4 (P < 0.001).
      Troponin returned to baseline value by T24. CONCLUSIONS: This study utilized a
      before and after study design where each horse served as its own control, as such
      the possible effect of regression to the mean cannot be ruled out. The reference
      intervals generated in this study may be used to identify selected
      echocardiographic and electrocardiographic abnormalities in racing horses
      receiving furosemide.

PMID- 29347922
TI  - Characteristics of individuals receiving disability benefits in the Netherlands
      and predictors of leaving the disability benefit scheme: a retrospective cohort
      study with five-year follow-up.
AB  - BACKGROUND: Today, work disability is one of the greatest social and labour
      market challenges for policy makers in most OECD countries, where on average,
      about 6% of the working-age population relies on disability benefits.
      Understanding of factors associated with long-term work disability may be helpful
      to identify groups of individuals at risk for disability benefit entitlement or
      continuing eligibility, and to develop effective interventions for these groups.
      The purpose of this study is to provide insight into the main diagnoses of
      workers who qualify for disability benefits and how these diagnoses differ in
      age, gender and education. Using a five-year follow-up, we examined the duration
      of disability benefits and how durations differ among individuals with various
      characteristics. METHODS: We performed a cohort study of 31,733 individuals
      receiving disability benefits from the Dutch Social Security Institute (SSI) with
      a five-year follow-up. Data were collected from SSI databases. Information about
      disorders was assessed by an insurance physician upon benefit application. These
      data were used to test for significant relationships among socio-demographics,
      main diagnoses and comorbidity, and disability benefit entitlement and continuing
      eligibility. RESULTS: Mental disorders were the most frequent diagnosis for
      individuals claiming work disability. Diagnoses differed among age groups and
      education categories. Mental disorders were the main diagnosis for work
      disability for younger and more highly educated individuals, and physical
      disorders (generally musculoskeletal, cardiovascular and cancer) were the main
      diagnosis for older and less educated individuals. In 82% of the claims, the
      duration of disability benefit was five years or more after approval. Outflow was
      lowest for individuals with (multiple) mental disorders and those with
      comorbidity of mental and physical disorders, and highest for individuals with
      (multiple) physical disorders. CONCLUSIONS: The main diagnosis for persons
      entitled to disability benefits was mental health problems, especially for young
      women. In a five-year follow-up, claim duration for disability benefits was long
      lasting for most claimants.

PMID- 29347923
TI  - Endoscopic balloon dilatation for benign hepaticojejunostomy anastomotic
      stricture using short double-balloon enteroscopy in patients with a prior
      Whipple's procedure: a retrospective study.
AB  - BACKGROUND: Endoscopic retrograde cholangiography using a short double-balloon
      endoscope (DB-ERC) is a promising minimally-invasive method for accessing
      hepaticojejunostomy (HJ) anastomosis in patients with surgically altered anatomy.
      We aimed to evaluate the immediate and long-term outcomes of balloon dilatation
      for benign HJ anastomotic stricture (HJAS) in patients who had previously
      undergone Whipple's procedure using a DB-ERC. METHODS: We conducted a
      retrospective analysis of 46 patients who underwent balloon dilatation alone with
      a DB-ERC for benign HJAS between November 2008 and November 2014. The median
      follow-up duration was 3.5 (interquartile range [IQR], 1.9-5.1) years. RESULTS:
      The technical and clinical success rates were 100%, and adverse events occurred
      in 7% (3/46, cholangitis). The median hospitalization period was seven (IQR, 5
      10) days. Of 42 patients (91%) followed-up for > 1 year, 24 (51%) had recurrent
      HJAS at a median of 1.2 (IQR, 0.6-2.9) years after balloon dilatation. The
      cumulative anastomotic patency rates at 1, 2, and 3 years were 73, 55, and 49%,
      respectively. In univariate analysis, early stricture formation (< 1 year) was a
      risk factor for recurrent stenosis, although no statistically significant risk
      factors were observed in multivariate analysis. CONCLUSIONS: Endoscopic balloon
      dilatation with DB-ERC for benign HJAS is effective and safe, having good
      immediate technical success and few adverse events. Further improvements to this
      procedure are needed to prevent recurrent HJAS.

PMID- 29347924
TI  - Causes of death in hospitalized children younger than 12 years of age in a
      Chinese hospital: a 10 year study.
AB  - BACKGROUND: In China, the majority (77%) of urban children die in hospitals.
      Hospital-based review could provide insight leading to improvements in clinical
      practice and increase the survival of critically ill children. The aim of the
      present study is to identify the trends of immediate causes and chronic
      underlying diseases associated with deaths of children at one of the largest
      teaching hospitals in China over a period of 10 years (2006-2015). METHODS: A
      retrospective analysis of data of all children aged 1 month to 11 years who died
      at Xinhua Hospital between 2006 and 2015. Demographic details, main causes of
      deaths, and chronic underlying diseases were reviewed. RESULTS: Case fatality
      rate was 0.55% (510/93,443) and it represented 0.41-0.80% deaths per year.
      Overall, the most common immediate causes of deaths in hospitalized children were
      pneumonia (36.7%), sepsis (13.5%), tumour (11.4%), followed by nontraumatic
      intracranial or gastrointestinal hemorrhage (10.6%) and cardiac shock (9.6%).
      Over 70% of the deaths in children were complicated with chronic underlying
      diseases. Congenital abnormality was the most frequent chronic underlying disease
      observed in infants (60.3%) and tumour was the main chronic underlying disease in
      toddlers (31.1%) and older children (44%). CONCLUSIONS: Infectious diseases,
      especially pneumonia, were the major immediate causes of deaths, and the
      mortality in the study population decreased with age. Tumour and other
      noninfectious disease accounted for more deaths in older children. Chronic
      underlying diseases were found in most deaths of children.

PMID- 29347925
TI  - Alarm pheromone and kairomone detection via bitter taste receptors in the mouse
      Grueneberg ganglion.
AB  - BACKGROUND: The mouse Grueneberg ganglion (GG) is an olfactory subsystem
      specialized in the detection of volatile heterocyclic compounds signalling
      danger. The signalling pathways transducing the danger signals are only beginning
      to be characterized. RESULTS: Screening chemical libraries for compounds
      structurally resembling the already-identified GG ligands, we found a new
      category of chemicals previously identified as bitter tastants that initiated
      fear-related behaviours in mice depending on their volatility and evoked neuronal
      responses in mouse GG neurons. Screening for the expression of signalling
      receptors of these compounds in the mouse GG yielded transcripts of the taste
      receptors Tas2r115, Tas2r131, Tas2r143 and their associated G protein alpha
      gustducin (Gnat3). We were further able to confirm their expression at the
      protein level. Challenging these three G protein-coupled receptors in a
      heterologous system with the known GG ligands, we identified TAS2R143 as a
      chemical danger receptor transducing both alarm pheromone and predator-derived
      kairomone signals. CONCLUSIONS: These results demonstrate that similar molecular
      elements might be used by the GG and by the taste system to detect chemical
      danger signals present in the environment.

PMID- 29347926
TI  - Handheld ultrasound to avert maternal and neonatal deaths in 2 regions of the
      Philippines: an iBuntis(r) intervention study.
AB  - BACKGROUND: The major causes of maternal and neonatal mortality in the
      Philippines are hemorrhages and obstructed labor due to placental implantation
      abnormalities (PIAs), twin pregnancies and fetal malpresentations. All of which
      are all easily detected by ultrasound. However, women in rural areas and low
      income groups do not have access to ultrasound during their prenatal care. We
      aimed to provide additional evidence on the benefits of handheld ultrasound (HU)
      for screening pregnancy related abnormalities in order to avert maternal and
      neonatal deaths. METHODS: Using a HU, we trained community healthcare workers
      (CHWs) to identify 5 obstetrical conditions: fetal viability and number,
      placental localization, amniotic fluid volume (AFV) and fetal presentation.
      Women, between 20th and 24th weeks age of gestation from 2 regions of the
      Philippines, were scanned using the HU and the GE Logic 5 Premium ultrasound
      machine for validation. Maternal and neonatal deaths averted were estimated as
      health outcome measures of the study. RESULTS: Four hundred sixty women were
      scanned of which 146 (31.7%) showed abnormal ultrasound readings consisting of 17
      PIAs, 123 fetal malpresentation, 3 twins and 3 AFV abnormalities. The use of HU
      could have possibly averted 29 (6.3%) maternal deaths and 14.6% neonatal deaths
      at the time of delivery. Thirty-two out of the 460 women (~7%) delivered at home
      and 93% in hospitals or birthing facilities/lying-in centers. We observed
      approximately 95% agreement between the ultrasound readings of the trainees and
      the trainers, and 99% agreement between the readings made from the HU with the
      validation machine. CONCLUSION: CHWs could be trained in the use of HU for
      scanning 5 obstetrical parameters. Early detection of abnormalities in these 5
      obstetrical parameters can lead to early referral to facilities that are better
      equipped to manage obstetrical emergencies. Prenatal ultrasound can be an
      excellent point of care test for screening pregnant women at risk for possible
      complications and even death during labor and delivery. TRIAL REGISTRATION: Thai
      Clinical Trial Registry identification number TCTR20171128004 , retrospectively
      registered November 28, 2017.

PMID- 29347927
TI  - Prevalence of hypertensive disorders of pregnancy in Ethiopia: a systemic review
      and meta-analysis.
AB  - BACKGROUND: Although hypertensive disorders of pregnancy are the leading cause of
      poor perinatal outcomes in Ethiopia, there is no study that shows the national
      prevalence. Therefore, the aim of this study was to estimate the national pooled
      prevalence of hypertensive disorders of pregnancy from studies conducted in
      different parts of the country. METHODS: Databases; MEDLINE, PubMed, HINARI,
      EMBASE, Google Scholar and African Journals Online were searched by using
      different search terms on HDP and Ethiopia. Joanna Briggs Institute Meta-Analysis
      of Statistics Assessment and Review Instrument was used for critical appraisal of
      studies. The analysis was done using STATA 14 software. The Cochran Q test and I2
      test statistics were used to test heterogeneity of studies. Egger's test was used
      to show the publication bias. The pooled prevalence of HDP and the odds ratio
      (OR) with 95% confidence interval was presented using forest plots. RESULT:
      Seventeen studies were included in this review, with a total of 258,602 pregnant
      women. The overall pooled prevalence of hypertensive disorders of pregnancy in
      Ethiopia was 6.07% (95% CI: 4.83%, 7.31%). The Subgroup analysis by region and
      year of study showed a higher prevalence of hypertensive disorders of pregnancy
      in Southern Nations, Nationalities, and Peoples' Region, 10.13% (95% CI = (8.5,
      12.43)), and reduction in the rate of HDP from 1990's to 2010's, 8.54% reducing
      to 5.71% respectively. The pooled prevalence of pregnancy-induced hypertension
      (PIH) and preeclampsia/eclampsia alone were 6.29 and 5.47 respectively. Pregnant
      women >= 35 years old are more likely to develop hypertensive disorders of
      pregnancy, OR = 1.64 (95% CI = (1.18, 2.28)). No statistically significant
      difference was observed between HDP and younger maternal age (less than 20 years
      old); OR = 2.92 (95% CI = (0.88, 9.70)). There was no association between
      hypertensive disorders of pregnancy and number of pregnancy, OR = 1.37 (95% CI =
      0.78, 2.41)). CONCLUSIONS: The prevalence of hypertensive disorders of pregnancy
      is high in Ethiopia. The problem is more common among older pregnant women (> 35
      years old). Government and other stakeholders should give due attention to an
      early screening of hypertension during pregnancy.

PMID- 29347928
TI  - Chronic obstructive pulmonary disease guidelines in Europe: a look into the
      future.
AB  - Clinical practice guidelines are ubiquitous and are developed to provide
      recommendations for the management of many diseases, including chronic
      obstructive pulmonary disease. The development of these guidelines is burdensome,
      demanding a significant investment of time and money. In Europe, the majority of
      countries develop their own national guidelines, despite the potential for
      overlap or duplication of effort. A concerted effort and consolidation of
      resources between countries may alleviate the resource-intensity of maintaining
      individual national guidelines. Despite significant resource investment into the
      development and maintenance of clinical practice guidelines, their implementation
      is suboptimal. Effective strategies of guideline dissemination must be given more
      consideration, to ensure adequate implementation and improved patient care
      management in the future.

PMID- 29347929
TI  - The HIV self-testing debate: where do we stand?
AB  - BACKGROUND: Emphasis on HIV testing as a gateway to prevention, treatment and
      care has grown tremendously over the past decade. In turn, this emphasis on
      testing has created a demand for new policies, programs, and technologies that
      can potentially increase access to and uptake of HIV testing. HIV self-testing
      (HST) technologies have gained important momentum following the approval of the
      over-the-counter self-tests in the United States, the UK, and France. While the
      renewed interest in HST has given rise to a number of high quality reviews of
      empirical studies conducted on this topic, we have yet to find an article that
      captures the extent of the debate on HST. MAPPING THE DEBATE: A critical review
      of the literature on HST was conducted and organized into three categories based
      on the focus of the article: 1) Empirical research, 2) Arguments, and 3) Context.
      We focused exclusively on the second category which included ethical analyses,
      policy analyses, editorials, opinion pieces, commentaries, letters to the editor
      and so forth. 10 lines of argument on HST were identified in the literature: 1)
      Individual - Public Health, 2) Strengths - Limits, 3) Benefits - Harms, 4)
      Screening - Testing, 5) Target - Market, 6) Health Care - Industry, 7) Regulation
      - Restriction, 8) Resource-Rich Settings - Resource-Limited Settings, 9) Ethical 
      Unethical, and 10) Exceptionalism - Normalization. Each line of argument is
      presented and discussed in the paper. CONCLUSION: We conclude by providing
      examples of critical questions that should be raised in order to take the debate
      to another level and generate new ways of thinking about HST.

PMID- 29347930
TI  - Risk factors for stillbirths: how much can a responsive health system prevent?
AB  - BACKGROUND: The stillbirth rate is an indicator of quality of care during
      pregnancy and delivery. Good quality care is supported by a functional heath
      system. The objective of this study was to explore the risk factors for
      stillbirths, particularly those related to a health system. METHODS: This case
      control study was conducted in two districts of Bihar, India. Information on
      cases (stillbirths) were obtained from facilities as reported by Health
      Management Information System; controls were consecutive live births from the
      same population as cases. Data were collected from 400 cases and 800 controls.
      The risk factors were compared using a hierarchical approach and expressed as
      odds ratio, attributable fractions and population attributable fractions.
      RESULTS: Of all the factors studied, 22 risk factors were independently
      associated with stillbirths. Health system-related factors were: administration
      of two or more doses of oxytocics to augment labour before reaching the
      facilities (OR 1.6; 95% CI 1.2-2.1), any complications during labour (OR 2.3;1.7
      3.1), >30 min to reach a facility from home (OR 1.4;1.05-1.8), >10 min to attend
      to the pregnant woman after reaching the facility (OR 2.8;1.7-4.5). In the final
      regression model, modifiable health system-related risk factors included: >10 min
      taken to attend to women after they reach the facilities (AOR 3.6; 95% CI 2.5
      5.1), untreated hypertension during pregnancy (AOR 2.9; 95% CI 1.5-5.6) and
      presence of any complication during labour, warranting treatment (AOR 1.7; 95% CI
      1.2-2.4). Among mothers who reported complications during labour, time taken to
      reach the facility was significantly different between stillbirths and live
      births (2nd delay; 33.5 min v/s 25 min; p < 0.001). Attributable fraction for any
      complication during labour was 0.56 (95% CI 0.42-0.67), >30 min to reach the
      facility 0.48 (95% CI 0.31-0.60) and institution of management 10 min after
      reaching the facility 0.68 (95% CI 0.58-0.75). Reaching a facility within 30 min,
      initiation of management within 10 min of reaching the facility and timely
      management of complications during labour could have prevented 17%, 37% and 20%
      of stillbirths respectively. CONCLUSION: A pro-active health system with
      accessible, timely and quality obstetric services can prevent a considerable
      proportion of stillbirths in low and middle income countries.

PMID- 29347931
TI  - Attitudes towards tooth fillings in Tanzanian adults and its association with
      previous filling experience.
AB  - BACKGROUND: Tooth filling treatment is utilized at low levels in many low and
      middle-income countries (LMICs), further, little is known about the prevailing
      attitudes towards such treatment. This study aimed to assess attitudes towards
      tooth filling among Tanzanian adults and how previous tooth filling experience is
      associated with these attitudes. METHODS: A pretested structured questionnaire
      was distributed among 1522 out-patients in four regional hospitals in Tanzania in
      2015-16. The questionnaire had eight statements on a 6-point Likert scale
      measuring attitudes towards tooth filling. Responses were analyzed independently
      and through a constructed attitude sum score. Linear regression analysis was used
      to assess the association of previous tooth fillings on attitudes towards tooth
      filling treatment. RESULTS: The respondents were mostly female (57.3%), with a
      mean age of 33.1 years (SD 11.3). About one third of the respondents (36.4%) had
      primary level of education. Attitudes towards tooth filling treatment were
      generally negative. Low levels of education and income were associated with more
      negative attitudes. A small proportion (11.5%) had a previous tooth filling.
      Having a previous tooth filling was associated with a more positive attitude
      towards tooth fillings regardless of socioeconomic status. CONCLUSIONS: This
      study shows that even in areas with limited resources and availability of
      services, previous experience of tooth fillings is related to more positive
      attitudes towards restorative treatment, which should be taken into account when
      planning oral health care programs.

PMID- 29347932
TI  - Epidemiology of arthritis, chronic back pain, gout, osteoporosis,
      spondyloarthropathies and rheumatoid arthritis among 1.5 million patients in
      Australian general practice: NPS MedicineWise MedicineInsight dataset.
AB  - BACKGROUND: Previous estimates for the prevalence of musculoskeletal conditions
      (MSK) and chronic pain in Australia have been based on self-report. We aimed to
      determine the prevalence and distribution of arthritis, chronic back pain, gout,
      osteoporosis, spondyloarthropathies and rheumatoid arthritis and current
      consultations for chronic pain among adults attending Australian general
      practice, and describe their distribution according to sociodemographic
      characteristics and presence of co-morbidities. METHODS: We investigated
      1,501,267 active adult patients (57.6% females; 22.5% >=65y) evaluated between
      2013 and 2016 and included in the MedicineInsight database (a National
      Prescribing Service MedicineWise program), a large general practice data program
      that extracts longitudinal de-identified electronic medical record data from
      'active' patients in over 550 practices. Three main groups of outcomes were
      investigated: 1) "prevalence" of arthritis, chronic back pain, gout,
      osteoporosis, spondyloarthropathies, and/or rheumatoid arthritis between 2000 and
      2016; 2) "current" diagnosis/encounter for the same conditions occurring between
      2013 and 2016, and; 3) "current" consultations for chronic pain of any type
      occurring between 2013 and 2016. RESULTS: The combined "prevalence" of the
      investigated MSK (diagnosis between 2000 and 2016) among adults attending
      Australian general practice was 16.8% (95%CI 15.9;17.7) with 21.3% (95%CI
      20.2;22.4) of the sample consulting for chronic pain between 2013 and 2016. The
      investigated MSK with the highest "prevalence" were arthritis (9.5%) and chronic
      back pain (6.7%). Patients with some of these MSK attended general practices more
      frequently than those without these conditions (median 2.0 and 1.0 contacts/year,
      respectively). The "prevalence" of the investigated MSK and "current"
      consultations for chronic pain increased with age, especially in women, but
      chronic pain remained stable at 22% for males aged > 40 years. The investigated
      MSK and chronic pain were more frequent among those in lower socioeconomic
      groups, veterans, Aboriginal and Torrent Strait Islanders, current and ex
      smokers, and patients with chronic obstructive pulmonary disease or heart
      failure. CONCLUSIONS: The investigated MSK are more frequent among lower
      socioeconomic groups and the elderly. Based on information collected from adults
      attending Australian general practices, MedicineInsight provided similar
      estimates to those obtained from population-based studies, with the advantage of
      being based on medical diagnosis and including a national sample.

PMID- 29347933
TI  - A systematic review on the use of healthcare services by undocumented migrants in
      Europe.
AB  - BACKGROUND: Undocumented migrants face particular challenges in accessing
      healthcare services in many European countries. The aim of this study was to
      systematically review the academic literature on the utilization of healthcare
      services by undocumented migrants in Europe. METHODS: The databases Embase,
      Medline, Global Health and Cinahl Plus were searched systematically to identify
      quantitative, qualitative and mixed methods studies published in 2007-2017.
      RESULTS: A total of 908 articles were retrieved. Deletion of duplicates left 531.
      After screening titles, abstracts and full texts according to pre-defined
      inclusion and exclusion criteria, 29 articles were included in the review.
      Overall, quantitative studies showed an underutilization of different types of
      healthcare services by undocumented migrants. Qualitative studies reported that,
      even when care was received, it was often inadequate or insufficient, and that
      many undocumented migrants were unfamiliar with their entitlements and faced
      barriers in utilizing healthcare services. CONCLUSIONS: Although it is difficult
      to generalize findings from the included studies due to methodological
      differences, they provide further evidence that undocumented migrants in Europe
      face particular problems in utilizing healthcare services.

PMID- 29347934
TI  - The predominant learning approaches of medical students.

PMID- 29347935
TI  - Real-world experience of women using extended-cycle vs monthly-cycle combined
      oral contraception in the United States: the National Health and Wellness Survey.
AB  - BACKGROUND: The real-world experience of women receiving extended-cycle combined
      oral contraception (COC) versus monthly-cycle COC has not been reported. METHODS:
      Data were from the United States 2013 National Health and Wellness Survey.
      Eligible women (18-50 years old, premenopausal, without hysterectomy) currently
      using extended-cycle COC (3 months between periods) were compared with women
      using monthly-cycle COC. Treatment satisfaction (1 "extremely dissatisfied" to 7
      "extremely satisfied"), adherence (8-item Morisky Medication Adherence Scale(c)),
      menstrual cycle-related symptoms, health-related quality of life (HRQOL) and
      health state utilities (Medical Outcomes Short Form Survey-36v2(r)), depression
      (9-item Patient Health Questionnaire), sleep difficulties, Work Productivity and
      Activity Impairment-General Health, and healthcare resource use were assessed
      using one-way analyses of variance, chi-square tests, and generalized linear
      models (adjusted for covariates). RESULTS: Participants included 260 (6.7%) women
      using extended-cycle and 3616 (93.3%) using monthly-cycle COC. Women using
      extended-cycle COC reported significantly higher treatment satisfaction (P =
      0.001) and adherence (P = 0.04) and reduced heavy menstrual bleeding (P = 0.029).
      A non-significant tendency toward reduced menstrual pain (39.5% versus 47.3%) and
      menstrual cycle-related symptoms (40.0% versus 48.7%) was found in women using
      extended-cycle versus monthly-cycle COC. Significantly more women using extended
      cycle COC reported health-related diagnoses, indicating preferential prescription
      for extended-cycle COC among women reporting more health problems. Consistent
      with this poorer health, more women using extended-cycle COC reported fatigue,
      headache, and activity impairment (P values < 0.05). There were no other
      significant differences between groups. CONCLUSIONS: This real-world
      observational study supports extended-cycle COC as a valuable treatment option
      with high satisfaction, high adherence, and reduced heavy menstrual bleeding.

PMID- 29347936
TI  - Comparative analysis of COPD associated with tobacco smoking, biomass smoke
      exposure or both.
AB  - BACKGROUND: Exposure to noxious gases and particles contained in both tobacco
      smoking (TS) and biomass smoke (BS) are well recognized environmental risk
      factors for chronic obstructive pulmonary disease (COPD). COPD is characterized
      by an abnormal inflammatory response, both in the pulmonary and systemic
      compartments. The differential effects of TS, BS or their combined exposure have
      not been well characterized yet. This study sought to compare the lung function
      characteristics and systemic inflammatory response in COPD patients exposed to
      TS, BS or their combination. METHODS: Sociodemographic, clinical and lung
      functional parameters were compared across 49 COPD patients with a history of
      smoking and no BS exposure (TS COPD), 31 never-smoker COPD patients with BS
      exposure (BS COPD), 46 COPD patients with a combined exposure (TS + BS COPD) and
      52 healthy controls (HC) who have never been exposed neither to TS or BS. Blood
      cell counts, C-reactive protein (CRP), fibrinogen and immunoglobulin E (IgE)
      levels were quantified in all four groups. RESULTS: TS + BS COPD patients
      exhibited significantly lower oxygen saturation than the rest of groups (p <
      0.01). Spirometry and diffusing capacity were significantly higher in BS than in
      TS or TS + BS patients. CRP levels were significantly higher in TS COPD patients
      than in BS COPD group (p < 0.05), whereas fibrinogen was raised in COPD patients
      with a history of smoking (TS and TS + BS) when compared to control subjects (p <
      0.01). Finally, COPD patients with BS exposure (BS and BS + TS groups) showed
      higher IgE levels than TS and HC (p < 0.05). CONCLUSIONS: There are significant
      physiological and inflammatory differences between COPD patients with TS, BS and
      TS + BS exposures. The latter had worse blood oxygenation, whereas the raised
      levels of IgE in BS exposed patients suggests a differential Th2 systemic
      inflammatory pattern triggered by this pollutant.

PMID- 29347937
TI  - Monoclonal antibody-based colloid gold immunochromatographic strip for the rapid
      detection of Tomato zonate spot tospovirus.
AB  - BACKGROUND: Tomato zonate spot virus (TZSV), a new species of genus Tospovirus,
      caused significant losses in yield and problems in quality of many important
      vegetables and ornamentals in Southwest China and posed a serious threat to
      important economic crops for the local farmers. A convenient and reliable method
      was urgently needed for rapid detection and surveillance of TZSV. METHODS: The
      nucleocapsid protein (N) of TZSV was expressed in Escherichia coli and purified,
      and was used as the antigen to immunize BALB/c mice. Three monoclonal antibodies
      (mAbs) 3A2, 5D2 and 5F7 against TZSV were obtained through the hybridoma
      technique. The mAb 3A2 was conjugated with colloid gold as detecting reagent; mAb
      5D2 was coated on a porous nitrocellulose membrane as the detection line and
      protein A was coated as the control line respectively. The colloid gold
      immunochromatographic (GICA) strip was assembled. RESULTS: The analysis of Dot
      ELISA and Western blot showed that the obtained three independent lines of mAbs
      3A2, 5D2 and 5F7 specifically recognized TZSV N. Based on the assembly of GICA
      strip, the detection of TZSV was achieved by loading the infected sap onto the
      test strip for visual inspection. The analysis could be completed within 5-10
      min. No cross-reaction occurred between TZSV and other tested viruses. The visual
      detection limit of the test strip for TZSV was 800 fold dilutions of TZSV
      infected leaf samples. CONCLUSION: The mAbs were specific and the colloidal GICA
      strip developed in this study was convenient, fast and reliable for the detection
      of TZSV. The method could be applied for the rapid diagnosis and surveillance of
      TZSV in the field.

PMID- 29347938
TI  - A survey of health problems of Nepalese female migrants workers in the Middle
      East and Malaysia.
AB  - BACKGROUND: Nepal is a key supplier of labour for countries in the Middle East,
      India and Malaysia. As many more men than women leave Nepal to work abroad,
      female migrant workers are a minority and very much under-researched. The aim of
      the study was to explore the health problems of female Nepalese migrants working
      in the Middle-East and Malaysia. METHODS: The study was conducted among 1010
      women who were registered as migrant returnees at an organisation called Pourakhi
      Nepal. Secondary data were extracted from the records of the organisation
      covering the five-year period of July 2009 to July 2014. RESULTS: The 1010
      participants were aged 14 to 51 with a median age of 31 (IQR: 38-25) years. A
      quarter of respondents (24%) reported having experienced health problems while in
      the country of employment. Fever, severe illness and accidents were the most
      common health problems reported. Working for unlimited periods of time and not
      being able to change one's place of work were independently associated with a
      greater likelihood of health problems. Logistic regression shows that migrant
      women who are illiterate [OR = 1.56, 95% CI: 1.02 to 2.38, p = 0.042], who had
      changed their workplace [OR = 1.63, 95% CI: 1.14 to 2.32, p = 0.007], who worked
      unlimited periods of time [OR = 1.64, 95% CI: 1.44 to 1.93, p = 0.020], had been
      severely maltreated or tortured in the workplace [OR = 1.84, 95% CI: 1.15 to
      2.92, p = 0.010], were not being paid on time [OR = 2.38, 95% CI: 1.60 to 3.55, p
      = 0.038] and migrant women who had family problems at home [OR = 3.48, CI 95%:
      1.22 to 9.98, p = 0.020] were significantly associated with health problems in
      their host country in the Middle East. CONCLUSION: Female migrant workers face
      various work-related health risks, which are often related to exploitation. The
      Government of Nepal should initiate awareness campaigns about health risks and
      rights in relation to health care services in the host countries. Recruiting
      agencies/employers should provide information on health risks and training for
      preventive measures. Raising awareness among female migrant workers can make a
      change in their working lives.

PMID- 29347939
TI  - Prevalence and management of severe asthma in primary care: an observational
      cohort study in Sweden (PACEHR).
AB  - BACKGROUND: Severe and uncontrolled asthma is associated with increased risk of
      exacerbations and death. A substantial proportion of asthma patients have poor
      asthma control, and a concurrent COPD diagnosis often increases disease burden.
      The objective of the study was to describe the prevalence and managemant of
      severe asthma in a Swedish asthma popuoation. METHODS: In this observational
      cohort study, primary care medical records data (2006-2013) from 36 primary
      health care centers were linked to data from national mandatory Swedish health
      registries. The studied population (>18 years) had a record of drug collection
      for obstructive pulmonary disease (ATC code R03) during 2011-2012, and a
      physician diagnosed asthma (ICD-10 code J45-J46) prior to drug collection. Severe
      asthma was classified as collection of high dose inhaled steroid (> 800
      budesonide or equivalent per day) and leukotriene receptor antagonist and/or long
      acting beta-agonist. Poor asthma control was defined as either collection of
      >=600 doses of short-acting beta-agonists, and/or >=1 exacerbation(s) during the
      year post index date. RESULTS: A total of 18,724 asthma patients (mean 49 years,
      62.8% women) were included, of whom 17,934 (95.8%) had mild to moderate and 790
      (4.2%) had severe asthma. Exacerbations were more prevalent in severe asthma
      (2.59 [2.41-2.79], Relative Risk [95% confidence interval]; p < 0.001). Poor
      asthma control was observed for 28.2% of the patients with mild to moderate
      asthma and for more than half (53.6%) of the patients with severe asthma
      (<0.001). Prior to index, one in five severe asthma patients had had a contact
      with secondary care and one third with primary care. A concurrent COPD diagnosis
      increased disease burden. CONCLUSION: Severe asthma was found in 4.2% of asthma
      patients in Sweden, more than half of them had poor asthma control, and most
      patients had no regular health care contacts.

PMID- 29347940
TI  - Domestic feline contribution in the transmission of Sporothrix in Rio de Janeiro
      State, Brazil: a comparison between infected and non-infected populations.
AB  - BACKGROUND: Sporotrichosis is a neglected zoonosis caused by pathogenic fungi
      belonging to the Sporothrix schenckii complex. In Rio de Janeiro state, this
      disease reached an epidemic status with over 4700 domestic felines and around
      4000 humans affected since the mid-90s. The present study evaluated clinical and
      epidemiological aspects and also the frequency of colonization and infection by
      these fungi in healthy cats and among those with suspicious cutaneous lesions,
      inhabiting four Rio de Janeiro state distinct areas. RESULTS: Three hundred and
      seventy-one cats were included in two groups: 175 healthy cats [CRG] and 196 cats
      showing lesions suggesting sporotrichosis [SSG]. Mycological diagnosis allowed
      SSG animals to be divided in positive [104 cats; +SG] and negative [92 cats; -SG]
      groups. Nails, oral mucosa and lesions swabs were submitted to culture and
      potential colonies were subculture for micromorphologycal analysis, dimorphism
      and molecular tests. In the CRG, only one cat was colonized in the oral cavity
      [0.57%]; in the -SG group, four animals showed colonization of the nail and/or
      oral cavity [4.3%]; while the highest frequency of colonization [39.4%] was
      observed in the +SG. All molecularly typed isolates were identified as S.
      brasiliensis. CONCLUSION: The results obtained here indicate that healthy cats
      have a minor role in sporotrichosis transmission within the state of Rio de
      Janeiro. Conversely, a higher participation of diseased feline in sporotrichosis
      transmission was evidenced, especially by the colonization of their oral cavity.
      Sporothrix brasiliensis equally affects and colonizes animals from distinct Rio
      de Janeiro state areas. Thus, we hypothesize that sporotrichosis is a uniform
      endemic throughout the state, whose transmission depends mainly on the contact
      with cats with sporotrichosis. Since Rio de Janeiro displays a world unique
      epidemic model of the disease, not fully understood, data on the infected and non
      infected animals can be of major importance for future strategies of
      sporotrichosis prevention and control. Finally, considering the importance of the
      current concept of "one health", the experience here observed can be helpful for
      distinct epizootias and/or zoonosis.

PMID- 29347941
TI  - A five-year retrospective study of the epidemiological characteristics and visual
      outcomes of pediatric ocular trauma.
AB  - BACKGROUND: Pediatric trauma can lead to serious visual impairment as a result of
      the trauma itself or secondary to amblyopia. Precise data on epidemiological
      characteristics and visual outcomes of pediatric ocular injuries are valuable for
      the prevention of monocular blindness. METHODS: A total of 268 cases of pediatric
      ocular trauma admitted to the Department of Ophthalmology of the Lithuanian
      University of Health Sciences Hospital from January 2008 to December 2013 were
      retrospectively reviewed. Data analysed included age, sex, cause, type and
      treatment of injury, initial and final visual acuity (VA) and tissues
      involvement. Eye injuries were classified by Birmingham Eye Trauma Terminology
      (BETT) and Ocular Trauma Classification System (OTCS). RESULTS: The age of
      children ranged from 6 months to 17.5 years. Boys were more likely to suffer
      ocular injury than girls. Home was the leading place of eye injury (60.4%),
      followed by outdoors (31.7%), school (5.2%) and sporting area (2.2%). The highest
      percentage of eye injuries in children were caused by blunt (40.3%) and sharp
      objects (29.9%), followed by burns (9.3%), falls (6.7%), explosions (4.5%),
      fireworks (4.1%), gunshots (1.9%) and traffic accidents (0.7%). Closed globe
      injury (CGI) was the most common type of eye injury (53.4%). CGI were noted to be
      higher in children aged 13-18 years, while open globe injury (OGI) were higher in
      the pre-school age group. Injury of grade 4 and grade 5 were more common in OGI,
      while grade 1 and grade 2 predominated in cases of CGI. Hypotony, traumatic
      cataract, iris laceration, vitreous prolapse and uveitis were the most common
      presentations of OGI, while hyphema, secondary glaucoma and retinal edema were
      significantly related with CGI. Final diagnoses contributing to poor final visual
      outcome such as corneal scar corneal opacity, hypotony, aphakia, and retinal
      detachment were statistically significant related only with OGI. Overall, 65.63%
      of children regained good visual acuity (VA >= 0.5), but for 18.4% of them, the
      trauma resulted in severe visual impairment (VA <= 0.1). CONCLUSION: Ocular
      trauma in children still remains an important preventable cause of ocular
      morbidity. This study provides data indicating that ophthalmological injuries are
      a significant cause of visual impairment in children.

PMID- 29347942
TI  - Infant and child mortality in relation to malaria transmission in KEMRI/CDC HDSS,
      Western Kenya: validation of verbal autopsy.
AB  - BACKGROUND: Malaria transmission reduction is a goal of many malaria control
      programmes. Little is known of how much mortality can be reduced by specific
      reductions in transmission. Verbal autopsy (VA) is widely used for estimating
      malaria specific mortality rates, but does not reliably distinguish malaria from
      other febrile illnesses. Overall malaria attributable mortality includes both
      direct and indirect deaths. It is unclear what proportion of the deaths averted
      by reducing malaria transmission are classified as malaria in VA. METHODS: Both
      all-cause, and cause-specific mortality reported by VA for children under 5 years
      of age, were assembled from the KEMRI/CDC health and demographic surveillance
      system in Siaya county, rural Western Kenya for the years 2002-2004. These were
      linked to household-specific estimates of the Plasmodium falciparum entomological
      inoculation rate (EIR) based on high resolution spatio-temporal geostatistical
      modelling of entomological data. All-cause and malaria specific mortality (by
      VA), were analysed in relation to EIR, insecticide-treated net use (ITN),
      socioeconomic status (SES) and parameters describing space-time correlation. Time
      at risk for each child was analysed using Bayesian geostatistical Cox
      proportional hazard models, with time-dependent covariates. The outputs were used
      to estimate the diagnostic performance of VA in measuring mortality that can be
      attributed to malaria exposure. RESULTS: The overall under-five mortality rate
      was 80 per 1000 person-years during the study period. Eighty-one percent of the
      total deaths were assigned causes of death by VA, with malaria assigned as the
      main cause of death except in the neonatal period. Although no trend was observed
      in malaria-specific mortality assessed by VA, ITN use was associated with reduced
      all-cause mortality in infants (hazard ratio 0.15, 95% CI 0.02, 0.63) and the EIR
      was strongly associated with both all-cause and malaria-specific mortality. 48.2%
      of the deaths could be attributed to malaria by analysing the exposure-response
      relationship, though only 20.5% of VAs assigned malaria as the cause and the
      sensitivity of VAs was estimated to be only 26%. Although VAs assigned some
      deaths to malaria even in areas where there was estimated to be no exposure, the
      specificity of the VAs was estimated to be 85%. CONCLUSION: Interventions that
      reduce P. falciparum transmission intensity will not only significantly reduce
      malaria-diagnosed mortality, but also mortality assigned to other causes in under
      5 year old children in endemic areas. In this setting, the VA tool based on
      clinician review substantially underestimates the number of deaths that could be
      averted by reducing malaria exposure in childhood, but has a reasonably high
      specificity. This suggests that malaria transmission-reducing interventions such
      as ITNs can potentially reduce overall child mortality by as much as twice the
      total direct malaria burden estimated from VAs.

PMID- 29347943
TI  - The factors that influence oral health-related quality of life in 15-year-old
      children.
AB  - BACKGROUND: Several hypotheses on factors that influence oral health-related
      quality of life (OHRQoL) have been proposed but a consensus has not been reached.
      This cross-sectional study aimed to analyse the sociodemographic and clinical
      factors that may influence the OHRQoL of 15-year-old children. METHODS: A
      representative sample was selected from Hong Kong. Periodontal status and caries
      were examined according to WHO criteria. Four orthodontic indices were used to
      assess malocclusion. Child Perception Questionnaire (CPQ11-14, 37 items)
      including four domains, namely oral symptoms (OS), functional limitations (FL),
      emotional well-being (EWB), and social well-being (SWB), was used to measure
      OHRQoL. Adjusted OR was calculated by ordinal logistic regression. RESULTS: A
      total of 364 eligible subjects (186 girls, 178 boys) were recruited. The
      prevalence of caries was higher in girls than in boys (P = 0.013). Compared with
      girls, boys tended to have a better experience in the domains of EWB, SWB and the
      total CPQ (adjusted OR = 0.46, 0.59 and 0.61, respectively). Unhealthy
      periodontal conditions were more prevalent than caries (92.6% vs. 52.7%);
      moreover, periodontal conditions with CPI scores of 2 had a negative effect on
      the domain of SWB and the total CPQ (adjusted OR = 1.76 and 1.71, respectively).
      Only the most severe malocclusion showed an effect on the domain of FL and the
      total CPQ (adjusted OR = 1.55 and 2.10, respectively). Little effect of family
      ecosocial factors and caries was found on CPQ scores. CONCLUSION: In this study,
      gender, periodontal status, and malocclusion showed an effect on OHRQoL after
      adjusting for potential confounders. Boys had less caries and better OHRQoL than
      girls did. Unhealthy periodontal conditions led to worse social welfares and
      OHRQoL. The most severe level of malocclusion caused oral functional limitations,
      hence worse OHRQoL.

PMID- 29347944
TI  - Expression of UGP2 and CFL1 expression levels in benign and malignant pancreatic
      lesions and their clinicopathological significance.
AB  - BACKGROUND: This study investigated UGP2 (uridine diphosphate-glucose
      pyrophosphorylase-2) and CFL1 (cofilin-1) expression in pancreatic ductal
      carcinoma (PDC), paracancerous tissue (PT), benign lesions (BL), and normal
      tissue (NT) and their clinicopathological significance. METHODS: Surgical
      specimens, which were collected from 106 cases of pancreatic ductal carcinoma, 35
      cases of paracancerous tissues, 55 cases of benign lesions and 13 cases of normal
      pancreatic tissues, were fixed with 4% formaldehyde to prepare conventional
      paraffin-embedded sections. EnVision immunohistochemical was used to stain for
      UGP2 and CFL1. Kaplan-Meier survival analysis was performed to assess the
      correlation of expression pattern with survival. RESULTS: We found that positive
      UGP2 and CFL1 expression in PDC were significantly higher than those in PT, BL,
      and NT. In PT and BL with positive UGP2 and CFL1 expression, mild to severe
      atypical hyperplasia or intraepithelial neoplasia of grades II-III was observed
      in ductal epithelium. Positive UGP2 and CFL1 expression in cases with high
      differentiation, no lymph node metastasis, no surrounding invasion, and TNM
      (tumor-node-metastasis) staging I or/and II were significantly lower than those
      in cases with poor differentiation, lymph node metastasis, surrounding invasion,
      and TNM stage III and/or IV. Positive UGP2 expression in male patients was
      significantly lower than that in female patients. UGP2 and CFL1 expression in PDC
      were positively correlated. Kaplan-Meier survival analysis showed the degree of
      differentiation, tumor maximal diameter, TNM stage, lymph node metastasis, and
      surrounding invasion, and UGP2 and CFL1 expression were closely related to the
      average survival time of patients with PDC. The survival time of patients with
      positive UGP2 and CFL1 expression was significantly shorter than that of patients
      with negative expression. Cox multivariate analysis showed that poor
      differentiation, tumor maximal diameter >= 3 cm, TNM stage III or IV, lymph node
      metastasis, surrounding invasion, and positive UGP2 and CFL1 expression was
      negatively correlated with the postoperative survival rate and positively
      correlated with the mortality of patients with PDC. CONCLUSION: Positive
      expression of UGP2 and CFL1 can serve a valuable prognostic factor in pancreatic
      cancer.

PMID- 29347946
TI  - Effects of long-term balance training with vibrotactile sensory augmentation
      among community-dwelling healthy older adults: a randomized preliminary study.
AB  - BACKGROUND: Sensory augmentation has been shown to improve postural stability
      during real-time balance applications. Limited long-term controlled studies have
      examined retention of balance improvements in healthy older adults after training
      with sensory augmentation has ceased. This pilot study aimed to assess the
      efficacy of long-term balance training with and without sensory augmentation
      among community-dwelling healthy older adults. METHODS: Twelve participants (four
      males, eight females; 75.6 +/- 4.9 yrs) were randomly assigned to the
      experimental group (n = 6) or control group (n = 6). Participants trained in
      their homes for eight weeks, completing three 45-min exercise sessions per week
      using smart phone balance trainers that provided written, graphic, and video
      guidance, and monitored trunk sway. During each session, participants performed
      six repetitions of six exercises selected from five categories (static standing,
      compliant surface standing, weight shifting, modified center of gravity, and
      gait). The experimental group received vibrotactile sensory augmentation for four
      of the six repetitions per exercise via the smart phone balance trainers, while
      the control group performed exercises without sensory augmentation. The smart
      phone balance trainers sent exercise performance data to a physical therapist,
      who recommended exercises on a weekly basis. Balance performance was assessed
      using a battery of clinical balance tests (Activity Balance Confidence Scale,
      Sensory Organization Test, Mini Balance Evaluation Systems Test, Five Times Sit
      to Stand Test, Four Square Step Test, Functional Reach Test, Gait Speed Test,
      Timed Up and Go, and Timed Up and Go with Cognitive Task) before training, after
      four weeks of training, and after eight weeks of training. RESULTS: Participants
      in the experimental group were able to use vibrotactile sensory augmentation
      independently in their homes. After training, the experimental group had
      significantly greater improvements in Sensory Organization Test and Mini Balance
      Evaluation Systems Test scores than the control group. Significant improvement
      was also observed for Five Times Sit to Stand Test duration within the
      experimental group, but not in the control group. No significant improvements
      between the two groups were observed in the remaining clinical outcome measures.
      CONCLUSION: The findings of this study support the use of sensory augmentation
      devices by community-dwelling healthy older adults as balance rehabilitation
      tools, and indicate feasibility of telerehabilitation therapy with reduced input
      from clinicians.

PMID- 29347945
TI  - MicroRNA transcriptome analysis of porcine vital organ responses to
      immunosuppressive porcine cytomegalovirus infection.
AB  - BACKGROUND: Porcine cytomegalovirus (PCMV) is an immunosuppressive virus that
      mainly inhibits T-lymphocyte and macrophage immune functions; it has
      significantly damaged the farming industry. Although recent studies have shown
      that miRNAs play important roles in immune responses, the regulatory mechanisms
      of miRNAs during immunosuppressive virus infection remain unclear. METHODS: In
      this study, porcine small-RNA transcriptomes of PCMV-infected and uninfected
      vital organs were first characterised by high-throughput sequencing. miRDeep2
      software was used to predict novel pig-encoded miRNAs. To verify the accuracy of
      the high-throughput sequencing results, stem-loop qRT-PCR was performed on 12
      significantly DE miRNAs. The physical and functional interactions between the
      immune-related target genes of the DE miRNAs in PCMV-infected organs were
      analysed using the STRING database. RESULTS: In total, 306 annotated and 295
      novel miRNAs were identified from PCMV-infected and uninfected porcine organs,
      respectively, through alignment with known Sus scrofa pre-miRNAs. Overall, 92,
      107, 95, 77 and 111 miRNAs were significantly differentially expressed in lung,
      liver, spleen, kidney and thymus after PCMV infection, respectively. According to
      Gene Ontology enrichment analysis, target genes of the differentially expressed
      miRNAs associated with immune system processes, regulation of biological
      processes and metabolic processes were enriched in every sample. Integrated
      expression analysis of the differentially expressed miRNAs and their target mRNAs
      in PCMV-infected thymus showed that the significant differential expression of
      specific miRNAs under the pressure of PCMV infection in central immune organs
      interfered with the expression of genes involved in important immune-related
      signalling pathways, thus promoting the viral infection. CONCLUSIONS: This is the
      first comprehensive analysis of the responses of host small-RNA transcriptomes to
      PCMV infection in vital porcine organs. It provides new insights into the
      regulatory mechanisms of miRNAs during infection by immunosuppressive viruses.

PMID- 29347947
TI  - Efficacy of pre-operative quadriceps strength training on knee-extensor strength
      before and shortly following total knee arthroplasty: protocol for a randomized,
      dose-response trial (The QUADX-1 trial).
AB  - BACKGROUND: Patients with knee osteoarthritis (OA) report knee pain, limitation
      in physical activities and low quality of life. The two primary treatments for
      knee OA are non-surgical treatment (e.g., exercise) and surgery (total knee
      arthroplasty (TKA)); however, national guidelines recommend non-surgical
      treatment to be tried prior to surgical procedures. Patients with knee OA are
      characterized by decreased muscle strength, particularly in the knee-extensor
      muscles. Correspondingly, decreased knee-extensor strength is found to be
      associated with an increased risk of development, progression and severity of
      knee OA symptoms. Recent trials suggest a positive effect of pre-operative
      exercise on pre- and post-operative outcome; however, the most effective pre
      operative knee-extensor strength exercise dosage is not known. The purpose of the
      present trial is to investigate the efficacy of three different exercise dosages
      of pre-operative, home-based, knee-extensor strength exercise on knee-extensor
      strength before and shortly after surgery in patients eligible for TKA due to end
      stage knee OA. METHODS: In this randomized dose-response trial with a three-arm
      parallel design, 140 patients with end-stage knee OA (candidates for TKA) are
      randomized to one of three exercise dosages (two, four or six session/week) of
      knee-extensor strength exercise (three sets, 12 repetitions at 12 RM, per
      exercise session) for 12 weeks. The knee-extensor strength exercise is home-based
      (unsupervised) and performed with an elastic exercise band following an initial
      exercise instruction. Adherence is objectively quantified using a sensor attached
      to the exercise band. The primary outcome will be the change in knee-extensor
      strength. Following the 12-week exercise period, the need for TKA surgery is re
      assessed by an orthopedic surgeon. DISCUSSION: Decreased knee-extensor strength
      is a major challenge in patients with knee OA. Exercise programs focusing on knee
      extensor strength are found to be more effective in relieving knee OA pain and
      symptoms compared to more general exercise programs. However, the optimal
      exercise dosage for knee-extensor strength deficits in patients with knee OA is
      inconclusive. Knowledge on the dose-response relationship for knee-extensor
      strength exercise in patients with knee OA will help guide future non-surgical
      treatment in this patient population. TRIAL REGISTRATION: ClinicalTrials.gov, ID:
      NCT02931058 . Pre-registered on 10 October 2016.

PMID- 29347948
TI  - Prenatal exposure to persistent organic pollutants and child overweight/obesity
      at 5-year follow-up: a prospective cohort study.
AB  - BACKGROUND: Prenatal exposure to persistent organic pollutants (POPs), may
      influence offspring weight gain. More prospective epidemiological studies are
      needed to compliment the growing body of evidence from animal studies. METHODS:
      Serum from 412 pregnant Norwegian and Swedish women participating in a
      Scandinavian prospective cohort study were collected in 1986-88, and analyses of
      two perfluoroalkyl substances (PFASs) and five organochlorines (OCs) were
      conducted. We used linear and logistic regression models with 95% confidence
      intervals (CIs) to evaluate the associations between maternal serum POP
      concentrations at 17-20 weeks of gestation and child overweight/obesity (body
      mass index (BMI) >= 85th percentile) at 5-year follow-up. Results were further
      stratified by country after testing for effect modification. We also assessed
      potential non-monotonic dose-response (NMDR) relationships. RESULTS: In adjusted
      linear models, we observed increased BMI-for-age-and-sex z-score (beta = 0.18,
      95% CI: 0.01-0.35), and increased triceps skinfold z-score (beta = 0.15, 95% CI:
      0.02-0.27) in children at 5-year follow-up per ln-unit increase in maternal serum
      perfluorooctane sulfonate (PFOS) concentrations. We observed increased odds for
      child overweight/obesity (BMI >= 85th percentile) for each ln-unit increase in
      maternal serum PFOS levels (adjusted OR: 2.04, 95% CI: 1.11-3.74), with stronger
      odds among Norwegian children (OR: 2.96, 95% CI: 1.42-6.15). We found similar
      associations between maternal serum perfluorooctanoate (PFOA) concentrations and
      child overweight/obesity. We found indications of NMDR relationships between PFOS
      and polychlorinated biphenyl (PCB) 153 and child overweight/obesity among Swedish
      children. CONCLUSION: We found positive associations between maternal serum PFAS
      concentrations and child overweight/obesity at 5-year follow-up, particularly
      among Norwegian participants. We observed some evidence for NMDR relationships
      among Swedish participants.

PMID- 29347949
TI  - Effects of surgery and anesthetic choice on immunosuppression and cancer
      recurrence.
AB  - BACKGROUND: The relationship between surgery and anesthetic-induced
      immunosuppression and cancer recurrence remains unresolved. Surgery and
      anesthesia stimulate the hypothalamic-pituitary-adrenal (HPA) axis and
      sympathetic nervous system (SNS) to cause immunosuppression through several tumor
      derived soluble factors. The potential impact of surgery and anesthesia on cancer
      recurrence was reviewed to provide guidance for cancer surgical treatment.
      METHODS: PubMed was searched up to December 31, 2016 using search terms such as,
      "anesthetic technique and cancer recurrence," "regional anesthesia and cancer
      recurrence," "local anesthesia and cancer recurrence," "anesthetic technique and
      immunosuppression," and "anesthetic technique and oncologic surgery." RESULTS:
      Surgery-induced stress responses and surgical manipulation enhance tumor
      metastasis via release of angiogenic factors and suppression of natural killer
      (NK) cells and cell-mediated immunity. Intravenous agents such as ketamine and
      thiopental suppress NK cell activity, whereas propofol does not. Ketamine induces
      T-lymphocyte apoptosis but midazolam does not affect cytotoxic T-lymphocytes.
      Volatile anesthetics suppress NK cell activity, induce T-lymphocyte apoptosis,
      and enhance angiogenesis through hypoxia inducible factor-1alpha (HIF-1alpha)
      activity. Opioids suppress NK cell activity and increase regulatory T cells.
      CONCLUSION: Local anesthetics such as lidocaine increase NK cell activity.
      Anesthetics such as propofol and locoregional anesthesia, which decrease surgery
      induced neuroendocrine responses through HPA-axis and SNS suppression, may cause
      less immunosuppression and recurrence of certain types of cancer compared to
      volatile anesthetics and opioids.

PMID- 29347950
TI  - The microRNA-15a-PAI-2 axis in cholangiocarcinoma-associated fibroblasts promotes
      migration of cancer cells.
AB  - BACKGROUND: Cholangiocarcinoma (CCA) has an abundance of tumor stroma which plays
      an important role in cancer progression via tumor-promoting signals. This study
      aims to explore the microRNA (miRNA) profile of CCA-associated fibroblasts (CCFs)
      and the roles of any identified miRNAs in CCA progression. METHODS: miRNA
      expression profiles of CCFs and normal skin fibroblasts were compared by
      microarray. Identified downregulated miRNAs and their target genes were confirmed
      by real-time PCR. Their binding was confirmed by a luciferase reporter assay. The
      effects of conditioned-media (CM) of miRNA mimic- and antagonist-transfected CCFs
      were tested in CCA migration in wound healing assays. Finally, the levels of
      miRNA and their target genes were examined by real-time PCR and
      immunohistochemistry in clinical CCA samples. RESULTS: miR-15a was identified as
      a downregulated miRNA in CCFs. Moreover, PAI-2 was identified as a novel target
      gene of miR-15a. Recombinant PAI-2 promoted migration of CCA cells. Moreover, CM
      from miR-15a mimic-transfected CCFs suppressed migration of CCA cells. Lower
      expression of miR-15a and higher expression of PAI-2 were observed in human CCA
      samples compared with normal liver tissues. Importantly, PAI-2 expression
      correlated with poor prognosis in CCA patients. CONCLUSIONS: These findings
      highlight the miR-15a/PAI-2 axis as a potential therapeutic target in CCA
      patients.

PMID- 29347951
TI  - Health-related quality of life among healthy elderly Iranians: a systematic
      review and meta-analysis of the literature.
AB  - BACKGROUND: Health-related quality of life (HRQoL) measurement in elderly people
      can provide appropriate information for an optimal management of physical/mental
      conditions. The main objective of the present study was to quantitatively assess
      the HRQoL among healthy elder Iranian individuals as measured by the Short-Form
      36 (SF-36) questionnaire, both overall and at the level of each its single
      component/domain. METHODS: This study was designed as a systematic review and
      meta-analysis, following the "Preferred Reporting Results of Systematic Reviews
      and Meta-Analyses" (PRISMA) guidelines. Embase, PubMed/MEDLINE, ISI/Web of
      Science (WOS), Scopus, and Iranian databases such as MagIran, SID and Irandoc
      were mined from inception up to 1st September 2017. Also the grey literature (via
      Google Scholar) was mined. Two reviewers independently screened titles/abstracts,
      assessed full-text articles, extracted data, and appraised their quality using
      the "Strengthening the Reporting of Observational Studies in Epidemiology"
      (STROBE) checklist. RESULTS: Twenty five studies were included. Mean overall
      HRQoL was 54.92 [95%CI 51.50-58.33], lower than the value found by studies done
      in other countries, especially in those economically developed. The sensitivity
      analysis indicated stability and reliability of results. Pooled scores of each
      HRQoL domain/sub-scale of the SF-36 questionnaire ranged from 49.77 (physical
      role functioning) to 63.02 (social role functioning). CONCLUSIONS: HRQoL among
      healthy elder Iranian individuals is generally low. Health policy-makers should
      put HRQoL among the elderly as a priority of their agenda, implementing ad hoc
      programs and providing social, economic and psychological support, as well as
      increasing the participation of old people in the community life and use their
      experiences.

PMID- 29347952
TI  - The German Quality Network Sepsis: study protocol for the evaluation of a quality
      collaborative on decreasing sepsis-related mortality in a quasi-experimental
      difference-in-differences design.
AB  - BACKGROUND: While sepsis-related mortality decreased substantially in other
      developed countries, mortality of severe sepsis remained as high as 44% in
      Germany. A recent German cluster randomized trial was not able to improve
      guideline adherence and decrease sepsis-related mortality within the
      participating hospitals, partly based on lacking support by hospital management
      and lacking resources for documentation of prospective data. Thus, more pragmatic
      approaches are needed to improve quality of sepsis care in Germany. The primary
      objective of the study is to decrease sepsis-related hospital mortality within a
      quality collaborative relying on claims data. METHOD: The German Quality Network
      Sepsis (GQNS) is a quality collaborative involving 75 hospitals. This study
      protocol describes the conduction and evaluation of the start-up period of the
      GQNS running from March 2016 to August 2018. Democratic structures assure
      participatory action, a study coordination bureau provides central support and
      resources, and local interdisciplinary quality improvement teams implement
      changes within the participating hospitals. Quarterly quality reports focusing on
      risk-adjusted hospital mortality in cases with sepsis based on claims data are
      provided. Hospitals committed to publish their individual risk-adjusted mortality
      compared to the German average. A complex risk-model is used to control for
      differences in patient-related risk factors. Hospitals are encouraged to
      implement a bundle of interventions, e.g., interdisciplinary case analyses,
      external peer-reviews, hospital-wide staff education, and implementation of rapid
      response teams. The effectiveness of the GQNS is evaluated in a quasi
      experimental difference-in-differences design by comparing the change of hospital
      mortality of cases with sepsis with organ dysfunction from a retrospective
      baseline period (January 2014 to December 2015) and the intervention period
      (April 2016 to March 2018) between the participating hospitals and all other
      German hospitals. Structural and process quality indicators of sepsis care as
      well as efforts for quality improvement are monitored regularly. DISCUSSION: The
      GQNS is a large-scale quality collaborative using a pragmatic approach based on
      claims data. A complex risk-adjustment model allows valid quality comparisons
      between hospitals and with the German average. If this study finds the approach
      to be useful for improving quality of sepsis care, it may also be applied to
      other diseases. TRIAL REGISTRATION: ClinicalTrials.gov NCT02820675.

PMID- 29347953
TI  - Effect of individual and community-level bed net usage on malaria prevalence
      among under-fives in the Democratic Republic of Congo.
AB  - BACKGROUND: Understanding the contribution of community-level long-lasting,
      insecticidal net (LLIN) coverage to malaria control is critical to planning and
      assessing intervention campaigns. The Democratic Republic of Congo (DRC), which
      has one of the highest burdens of malaria cases and deaths and has dramatically
      scaled up LLIN ownership in recent years thus it is an ideal setting to evaluate
      the effect of individual versus community-level use to prevent malaria among
      children under the age of 5. RESULTS: Data were derived from the 2013-2014 DRC
      Demographic and Health Survey. Community-level LLIN usage was significantly
      associated with protection against malaria, even when individual-level LLIN usage
      was included in the model. In stratified analysis, higher levels of community
      LLIN coverage enhanced the protective effect of individual LLIN usage, resulting
      in lower malaria prevalence among individuals who used a LLIN. A sub-analysis of
      individual LLIN usage by insecticide type revealed deltamethrin-treated nets were
      more protective than permethrin-treated nets, suggesting that mosquitoes in the
      DRC are more susceptible to deltamethrin. CONCLUSIONS: This study examines the
      effects of individual and community-level LLIN usage in young children in an area
      of high ITN usage. Individual and community LLIN usage were significantly
      associated with protection against malaria in children under 5 in the DRC.
      Importantly, the protective effect of individual LLIN usage against malaria is
      enhanced when community LLIN coverage is higher, demonstrating the importance of
      increasing community-level LLIN usage. LLINs treated with deltamethrin were shown
      to be more protective against malaria than LLINs treated with permethrin.
      Demographic and Health Surveys are thus a novel and important means of
      surveillance for insecticide resistance.

PMID- 29347955
TI  - Clinical outcomes of a combined transcatheter and minimally invasive atrial
      septal defect repair program using a 'Heart Team' approach.
AB  - BACKGROUND: Contemporary transcatheter and minimally invasive approaches allow
      for improved cosmesis and eliminate sternotomy; however, access to a 'Heart Team'
      approach to minimally invasive atrial septal defect (ASD) repair remains limited
      in Canada. METHODS: Retrospective chart review of all minimally invasive atrial
      septal defect repairs performed between 2009 and 2017 at a quaternary cardiac
      care centre were included. We compared residual shunt, functional status,
      periprocedural complications, and hospital lengths-of-stay between patients
      undergoing transcatheter and minimally invasive endoscopic ASD repair. RESULTS:
      Between 2009 and 2017, 61 consecutive patients underwent ASD repair at a single
      centre: 28 patients underwent transcatheter closure (64.3% female; median age 57,
      interquartile range 43-70.5) and 33 patients underwent minimally invasive
      endoscopic repair (72.7% female; median age 37, interquartile range 24-50).
      Patient demographics were similar between the two groups with the exception of
      transcatheter patients having smaller defect size (1.65 cm versus 2.35 cm, p =
      0.002). Procedural success was 93% (26/28) and 100% (33/33) for transcatheter and
      minimally invasive groups (p = 0.21), respectively. Periprocedural complications
      were similarly low between the two groups with the exception of longer hospital
      length-of-stay in the surgical patients (5 days vs 1 day, p < 0.0001). Over a
      follow-up period (transcatheter: 0.5-56.5 months, surgical: 0.25-89 months),
      there was no difference in residual shunt (14.3% versus 6.1%, p = 0.4) or NYHA I
      Functional Class (88.5% versus 96.9%, p = 0.21). CONCLUSION: Transcatheter and
      minimally invasive approaches to ASD repair are safe and feasible in selected
      patients using a 'Heart Team' approach and represent attractive alternatives to
      median sternotomy.

PMID- 29347954
TI  - A reverse vaccinology approach to the identification and characterization of
      Ctenocephalides felis candidate protective antigens for the control of cat flea
      infestations.
AB  - BACKGROUND: Despite the abundance of the domestic cat flea, Ctenocephalides felis
      (Bouche, 1835) and disease risks associated with them, flea control is difficult
      and requires the development of new control interventions such as vaccines. In
      this study, a reverse vaccinology approach was designed to achieve a rational
      selection of cat flea candidate protective antigens. METHODS: Based on
      transcriptomics and proteomics data from unfed adult fleas it was possible to
      select more specific candidate protective antigens based on highly represented
      and functionally relevant proteins present in the predicted exoproteome. The
      protective capacity of the recombinant antigens was evaluated for the control of
      C. felis infestations in vaccinated cats. RESULTS: Vaccination with recombinant
      antigens induced an antibody response in immunized cats. Furthermore, a
      correlation was obtained between the effect of vaccination (antibody levels) and
      vaccine efficacy on flea phenotype (egg hatchability). The results suggested that
      the main effect of vaccination with these antigens was on reducing cat flea egg
      hatchability and fertility, with an overall vaccine efficacy of 32-46%. Although
      vaccination with these antigens did not have an effect on flea infestations,
      vaccines affecting reproductive capacity could reduce cat flea populations,
      particularly under conditions of direct insect transmission between cats.
      CONCLUSIONS: These results support the development of vaccines with protective
      antigens affecting flea reproduction and development after feeding on immunized
      animals for the control of cat flea infestations.

PMID- 29347956
TI  - What should be included in the assessment of laypersons' paediatric basic life
      support skills? Results from a Delphi consensus study.
AB  - BACKGROUND: Assessment of laypersons' Paediatric Basic Life Support (PBLS) skills
      is important to ensure acquisition of effective PBLS competencies. However
      limited evidence exists on which PBLS skills are essential for laypersons. The
      same challenges exist with respect to the assessment of foreign body airway
      obstruction management (FBAOM) skills. We aimed to establish international
      consensus on how to assess laypersons' PBLS and FBAOM skills. METHODS: A Delphi
      consensus survey was conducted. Out of a total of 84 invited experts, 28 agreed
      to participate. During the first Delphi round experts suggested items to assess
      laypersons' PBLS and FBAOM skills. In the second round, the suggested items
      received comments from and were rated by 26 experts (93%) on a 5-point scale (1 =
      not relevant to 5 = essential). Revised items were anonymously presented in a
      third round for comments and 23 (82%) experts completed a re-rating. Items with a
      score above 3 by more than 80% of the experts in the third round were included in
      an assessment instrument. RESULTS: In the first round, 19 and 15 items were
      identified to assess PBLS and FBAOM skills, respectively. The ratings and
      comments from the last two rounds resulted in nine and eight essential assessment
      items for PBLS and FBAOM skills, respectively. The PBLS items included:
      "Responsiveness"," Call for help", "Open airway"," Check breathing", "Rescue
      breaths", "Compressions", "Ventilations", "Time factor" and "Use of AED". The
      FBAOM items included: "Identify different stages of foreign body airway
      obstruction", "Identify consciousness", "Call for help", "Back blows", "Chest
      thrusts/abdominal thrusts according to age", "Identify loss of consciousness and
      change to CPR", "Assessment of breathing" and "Ventilation". DISCUSSION: For
      assessment of laypersons some PBLS and FBAOM skills described in guidelines are
      more important than others. Four out of nine of PBLS skills focus on airway and
      breathing skills, supporting the major importance of these skills for laypersons'
      resuscitation attempts. CONCLUSIONS: International consensus on how to assess
      laypersons' paediatric basic life support and foreign body airway obstruction
      management skills was established. The assessment of these skills may help to
      determine when laypersons have acquired competencies. TRIAL REGISTRATION: Not
      relevant.

PMID- 29347957
TI  - High parasite burden increases the surfacing and mortality of the manila clam
      (Ruditapes philippinarum) in intertidal sandy mudflats on the west coast of Korea
      during hot summer.
AB  - BACKGROUND: Over the past few decades, mass mortality events of Manila clams have
      been reported from several tidal flats on the west coast of Korea during hot
      summers. During such mortality events, once clams simultaneously surface, they
      fail to re-burrow, perishing within a week. The present study aimed to identify
      the possible causes of the mass mortality of this clam species by investigating
      the Perkinsus olseni parasite burden and immune parameters of surfaced clams (SC)
      and normal buried clams (NBCs) when sea water or sediment temperature in the
      study area varied from 25  degrees C to 34  degrees C from late July through mid
      August 2015. RESULTS: We collected 2 groups of clams distributed within a 10-m2
      area when a summer clam mortality event occurred around Seonyu-do Island on the
      west coast of Korea in 2015. The clams were collected 2 days after they surfaced
      on the sediment and still looked healthy without any gaping. The clams were
      transported to the laboratory, and we compared P. olseni infection intensity and
      cell-mediated hemocyte parameters between the NBCs and SCs. SCs showed
      significantly higher levels of P. olseni burden, lower condition index, and lower
      levels of cell-mediated immune functions than those of NBCs. CONCLUSIONS: Our
      study suggests that high P. olseni infection weakens Manila clams' resistance
      against thermal stress, causing them to surface. We surmise that the summer mass
      mortality of Manila clams on the west coast of Korea is caused by the combined
      effects of high P. olseni infection levels and abnormally high water temperature
      stress.

PMID- 29347958
TI  - Correlation of structural defects in the ascending aortic wall to ultrasound
      parameters: benefits for decision-making process in aortic valve surgery.
AB  - BACKGROUND: Histopathological changes in the ascending aorta wall in patients
      with severe tricuspid aortic valve (TAV) stenosis were graded and correlated to
      echocardiographic parameters. Objective was to associate threshold
      echocardiographic values with structural defects in the ascending aorta providing
      a tool to improve decision-making process in cases when simultaneous aortic valve
      replacement (AVR) and ascending aorta replacement is considered. METHODS:
      Biopsies from 108 TAV stenosis patients subjected to AVR were graded into three
      grades according to severity of aortic wall changes. Echocardiographic parameters
      obtained preoperatively and correlated to grade, age, gender and risk factors,
      were diameters of ventriculo-aortic junction (AA), sinus Valsalva (SV),
      sinotubular junction (STJ), the largest diameter of the visualized ascending
      aorta (AscA) as well as indexes: sinus Valsalva (SVI), sinotubular junction
      (STJI), AscA/AA and STJ/AA. RESULTS: Two echocardiographic parameters portrayed
      grades with statistical significance: STJ (F = 5.417; p = 0.006 (p < 0.05)) and
      AscA (F = 3.924; p = 0.023 (p < 0.05)). By using multiple predictors in the
      setting of Regression analysis, statistically significant differences among
      grades were reached for AA, SV, STJ, AscA and SVI. With further ROC curves
      analysis, threshold values for different grades were recognized. Grade 2 is
      identified in patients with AscA > 3.3 cm, while Grade 3 is identified in
      patients with values of AscA > 3.5 cm, STJ > 2.9 cm and STJI > 1. CONCLUSIONS:
      Hemodynamic stress induced by TAV stenosis leads to elastic lamellae disruption
      in the aortic wall. Those changes could be graded and correlated with
      echocardiographic parameters of the aortic root and ascending aorta, providing a
      tool for decision to replace ascending aorta concomitantly with AVR.

PMID- 29347959
TI  - Influence of Schistosoma japonicum programmed cell death protein 10 on the growth
      and development of schistosomula.
AB  - BACKGROUND: Schistosomiasis caused by Schistosoma japonicum is among the most
      serious endemic zoonoses in China. To study interactions between schistosomula,
      the pre-adult juvenile stage, and hosts, it is important to study the functions
      of key genes involved in schistosomula growth and development. Programmed cell
      death protein 10 (pcdp10) is an important apoptosis-related gene with various
      biological functions. This study described the molecular characterization of S.
      japonicum PCDP10 (SjPCDP10) and evaluated its functions in schistosomula.
      METHODS: Real-time quantitative polymerase chain reaction (qPCR) and western blot
      were used to detect Sjpcdp10 mRNA and protein levels, respectively, at different
      developmental stages. Immunolocalization was performed to determine SjPCDP10
      expression in the parasite. RNA interference (RNAi) experiments were used to
      assess gene functions associated with SjPCDP10 in schistosomula growth and
      development. RESULTS: Real-time qPCR revealed that Sjpcdp10 was expressed during
      all investigated developmental stages and upregulated during schistosomula growth
      and development. Histochemical localization showed that SjPCDP10 was mainly
      distributed in the teguments of schistosomula in all investigated stages and part
      of the parenchymal area of 14-, 18-, and 21-day-old schistosomula. Following
      Sjpcdp10 knockdown by RNAi, the lengths, widths, areas, and volumes of
      schistosomula were significantly lower than those in the control group. Scanning
      electron microscopy showed that the body surfaces of schistosomula subjected to
      RNAi were seriously damaged, with few tegumental spines and sensory papillae.
      Transmission electron microscopy indicated that the teguments of Sjpcdp10
      knockdown schistosomula were incomplete, the number of layers was reduced, and
      the thickness decreased significantly as compared with those in the control
      group. Furthermore, terminal deoxynucleotidyl transferase dUTP nick-end labelling
      results showed that the rate of apoptosis in Sjpcdp10-knockdown schistosomula was
      significantly higher than that in the control group. CONCLUSIONS: Sjpcdp10
      knockdown influenced the growth and development of schistosomula. Therefore, our
      results indicated that SjPCDP10 contributes to the regulation of cell apoptosis
      and is essential for schistosomula growth and development.

PMID- 29347960
TI  - Long-term outcome of definitive radiotherapy for cervical esophageal squamous
      cell carcinoma.
AB  - BACKGROUND: The aim of this study was to identify the long-term clinical outcome
      of definitive radiotherapy using three-dimensional conformal radiotherapy (3DCRT)
      for cervical esophageal squamous cell carcinoma (CESCC). METHODS: We
      retrospectively reviewed the medical records of 30 patients with CESCC [clinical
      stage I/II/III/IV(M1LYM); 3/2/12/13] (TNM 7th edition) who underwent definitive
      radiotherapy using 3DCRT between 2000 and 2014 in our institution. The median
      prescribed dose for the gross tumor and metastatic lymph nodes was 60 Gy. Twenty
      six patients underwent elective nodal irradiation for the neck node levels III,
      IV, and VI and for upper mediastinal lymph nodes with a median dose of 40 Gy.
      Twenty-six patients underwent concurrent chemotherapy. Initial disease
      progression sites, locoregional control (LRC) rate, overall survival (OS) rate,
      and toxicities were retrospectively evaluated. A univariate analysis was
      performed to identify prognostic factors. RESULTS: With a median follow-up of 110
      months, the 5- and 10-year LRC rates were 43.7% and 37.4%, respectively. The 5-
      and 10-year OS rates were 48.3% and 40.2%, respectively. Locoregional, distant
      and both area accounted for 83%, 6% and 11% of the initial progression sites.
      Unresectable status and M1LYM were significantly associated with poor LRC (p <
      0.05) and OS (p < 0.05). Grade 3 acute non-hematological toxicity occurred in
      13.3% of patients. During the follow-up, patients without any disease progression
      did not need a permanent gastrostomy tube or tracheostomy. Late toxicity events,
      including hypothyroidism and cardiovascular disease, were observed; 5- and 10
      year cumulative incidence rates of grade 2 hypothyroidism and >=grade 3
      cardiovascular disease were 31.6% and 62.5%, and 17.5% and 21.3%, respectively.
      CONCLUSIONS: Definitive radiotherapy yields a cure for patients with CESCC while
      preserving their laryngopharyngeal function. The poor LRC rate in the advanced
      stage needs to be overcome for a better prognosis. As the incidence of radiation
      induced hypothyroidism and cardiovascular disease was not low, long-term
      survivors should be followed up for these symptoms.

PMID- 29347961
TI  - Relevant pericardial effusion caused by cytomegalovirus infection in an
      immunocompetent patient: a case report.
AB  - BACKGROUND: Cytomegalovirus infection is known to cause symptomatic disease in
      immunocompromised patients, while an infection in immunocompetent individuals
      normally causes few or no symptoms. We present the case of an immunocompetent
      adult patient with unexpected severe evolution. CASE PRESENTATION: An otherwise
      healthy, 72-year-old Caucasian woman presented with complaints of progressive
      shoulder pain and dyspnoea on exertion. The blood test results showed elevated
      inflammation parameters and elevated hepatic transaminase levels. Radiologic
      examinations were carried out, and the computed tomography scan revealed a
      hepatomegaly and a chest X-ray showed evidence of a unilateral pleural effusion.
      A transthoracic echocardiography detected pericardial effusion with consecutive
      hemodynamic changes. Since it was considered that using ultrasound-guided
      pericardiocentesis could significantly increase the risk of liver injury due to
      hepatomegaly, a pericardial window was performed instead. Further investigation
      showed that our patient tested positive for an acute cytomegalovirus infection in
      the serologic tests. Laboratory findings included new evidence of immunoglobulin
      M seroconversion and high immunoglobulin G avidity, so we considered the
      possibility that a former cytomegalovirus infection may be coexisting with a new
      cytomegalovirus reinfection. CONCLUSIONS: In immunocompetent individuals, a
      symptomatic cytomegalovirus primary infection or reinfection should be considered
      in patients presenting with pericardial effusion and serositis.

PMID- 29347962
TI  - Primary explant culture and collagen I substrate enhances corneal endothelial
      cell morphology.
AB  - OBJECTIVES: Corneal endothelial cell (CEC) isolation and harvest aim to produce
      engineered grafts to solve donor corneal tissue shortage. To yield high amounts
      of CEC maintaining morphological and molecular characteristics, several isolation
      and culture conditions are reported. Here, we combined direct explant culture,
      with three different coating conditions and a two-step media approach to compare
      confluence efficiency, morphology, and specific molecular markers expression.
      DATA DESCRIPTION: Confluence was reached after 2 weeks in the three coating
      conditions (Matrigel, collagen I, and in uncoated plates) using a two-step
      approach (proliferative medium without pituitary extract, followed by stabilizer
      basal medium). Na/K-ATPase and GPC4 markers were detected by immunocytochemistry
      while GPC4, CD200, and TJP1 by RT-PCR in the three CEC coating culture
      conditions. CEC in proliferative medium showed spindle morphology in the three
      conditions. Polygonal morphology was seen in CEC cultures using basal medium
      under uncoated and collagen I coated plates. CEC cultured in Matrigel-coated
      plates remained with spindle morphology in basal medium.

PMID- 29347963
TI  - Hungry to learn: the prevalence and effects of food insecurity on health
      behaviors and outcomes over time among a diverse sample of university freshmen.
AB  - BACKGROUND: To examine longitudinal associations between food insecurity (FI) and
      health behaviors/outcomes among a diverse sample of university freshmen. METHODS:
      Freshman students (n = 1138; 65% female; 49% non-white) participating in the
      Social impact of Physical Activity and nutRition in College study completed
      surveys on health behaviors and had height/weight measured up to 4 times (T1-T4)
      in Arizona during 2015-2016. Structural equation models were estimated to
      determine if, after adjusting for covariates, FI predicted concurrent
      behaviors/outcomes and subsequent behaviors/outcomes. Analyses reported here were
      conducted in 2017. RESULTS: The prevalence of FI was significantly higher at the
      end of each semester (35% and 36%, respectively) than at the start of the year
      (28%). Longitudinally, FI was not related to any health behaviors/outcomes at
      future time points. However, FI was significantly and inversely associated with
      concurrent breakfast consumption on most days of the week (OR = 0.67, 99% CI =
      0.46, 0.99), daily evening meal consumption (OR = 0.55, 99% CI = 0.36, 0.86)
      healthy eating habits on campus (OR = 0.68, 99% CI = 0.46, 1.00), healthy
      physical activity habits on campus (OR = 0.66, 99% CI = 0.44, 1.00), and
      positively related to the likelihood of experiencing stress (OR = 1.69, 99% CI =
      1.16, 2.46) and depressed mood (OR = 1.98, 99% CI = 1.34, 2.91). CONCLUSIONS:
      Compared with US prevalence rates, the sample FI prevalence was high. FI was
      related to poorer eating patterns, physical activity behaviors, and mental
      health, even after adjusting for prior levels of behavior.

PMID- 29347964
TI  - Correction to expert consensus on re-irradiation for recurrent glioma.
AB  - In the original publication [1] two author names were missing the middle names.
      The corrected versions can be found in this Erratum.

PMID- 29347965
TI  - Characterization of highly virulent multidrug resistant Vibrio cholerae isolated
      from a large cholera outbreak in Ghana.
AB  - OBJECTIVE: The purpose of this study was to investigate the virulent factors of
      Vibrio cholerae which caused an unprecedented large cholera outbreak in Ghana in
      2014 and progressed into 2015, affected 28,975 people with 243 deaths. RESULTS:
      The V. cholerae isolates were identified to be the classical V. cholerae 01
      biotype El Tor, serotype Ogawa, responsible for the large cholera outbreak in
      Ghana. These El Tor strains bear CtxAB and Tcp virulent genes, making the strains
      highly virulent. The strains also bear SXT transmissible element coding their
      resistance to antibiotics, causing high proportions of the strains to be
      multidrug resistant, with resistant proportions of 95, 90 and 75% to
      trimethoprim/sulfamethoxazole, ampicillin and ceftriaxone respectively. PFGE
      patterns indicated that the isolates clustered together with the same pattern and
      showed clusters similar to strains circulating in DR Congo, Cameroun, Ivory Coast
      and Togo. The strains carried virulence genes which facilitated the disease
      causation and spread. This is the first time these virulent genes were determined
      on the Ghanaian Vibrio strains.

PMID- 29347966
TI  - ReprDB and panDB: minimalist databases with maximal microbial representation.
AB  - BACKGROUND: Profiling of shotgun metagenomic samples is hindered by a lack of
      unified microbial reference genome databases that (i) assemble genomic
      information from all open access microbial genomes, (ii) have relatively small
      sizes, and (iii) are compatible to various metagenomic read mapping tools.
      Moreover, computational tools to rapidly compile and update such databases to
      accommodate the rapid increase in new reference genomes do not exist. As a
      result, database-guided analyses often fail to profile a substantial fraction of
      metagenomic shotgun sequencing reads from complex microbiomes. RESULTS: We report
      pipelines that efficiently traverse all open access microbial genomes and
      assemble non-redundant genomic information. The pipelines result in two species
      resolution microbial reference databases of relatively small sizes: reprDB, which
      assembles microbial representative or reference genomes, and panDB, for which we
      developed a novel iterative alignment algorithm to identify and assemble non
      redundant genomic regions in multiple sequenced strains. With the databases, we
      managed to assign taxonomic labels and genome positions to the majority of
      metagenomic reads from human skin and gut microbiomes, demonstrating a
      significant improvement over a previous database-guided analysis on the same
      datasets. CONCLUSIONS: reprDB and panDB leverage the rapid increases in the
      number of open access microbial genomes to more fully profile metagenomic
      samples. Additionally, the databases exclude redundant sequence information to
      avoid inflated storage or memory space and indexing or analyzing time. Finally,
      the novel iterative alignment algorithm significantly increases efficiency in pan
      genome identification and can be useful in comparative genomic analyses.

PMID- 29347967
TI  - Data quality and feasibility of the Experience Sampling Method across the
      spectrum of severe psychiatric disorders: a protocol for a systematic review and
      meta-analysis.
AB  - BACKGROUND: Due to a number of methodological advantages and theoretical
      considerations, more and more studies in clinical psychology research employ the
      Experience Sampling Method (ESM) as a data collection technique. Despite this
      growing interest, the absence of methodological guidelines related to the use of
      ESM has resulted in a large heterogeneity of designs while the potential effects
      of the design itself on the response behavior of the participants remain unknown.
      The objectives of this systematic review are to investigate the associations
      between the design characteristics and the data quality and feasibility of
      studies relying on ESM in severe psychiatric disorders. METHODS: We will search
      for all published studies using ambulatory assessment with patients suffering
      from major depressive disorder, bipolar disorder, and psychotic disorder or
      individuals at high risk for these disorders. Electronic database searches will
      be performed in PubMed and Web of Science with no restriction on the publication
      date. Two reviewers will independently screen original studies in a
      title/abstract phase and a full-text phase based on the inclusion criteria. The
      information related to the design and sample characteristics, data quality, and
      feasibility will be extracted. We will provide results in terms of a descriptive
      synthesis, and when applicable, a meta-analysis of the findings will be
      conducted. DISCUSSION: Our results will attempt to highlight how the feasibility
      and data quality of ambulatory assessment might be related to the methodological
      characteristics of the study designs in severe psychiatric disorders. We will
      discuss these associations in different subsamples if sufficient data are
      available and will examine limitations in the reporting of the methods of
      ambulatory studies in the current literature. SYSTEMATIC REVIEW REGISTRATION: The
      protocol for this systematic review was registered on PROSPERO (PROSPERO 2017:
      CRD42017060322 ) and is available in full on the University of York website (
      http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42017060322 ).

PMID- 29347968
TI  - 18F-FDG-PET/CT and diffusion-weighted MRI for monitoring a BRAF and CDK 4/6
      inhibitor combination therapy in a murine model of human melanoma.
AB  - BACKGROUND: The purpose of the study was to investigate a novel BRAF and CDK 4/6
      inhibitor combination therapy in a murine model of BRAF-V600-mutant human
      melanoma monitored by 18F-FDG-PET/CT and diffusion-weighted MRI (DW-MRI).
      METHODS: Human BRAF-V600-mutant melanoma (A375) xenograft-bearing balb/c nude
      mice (n = 21) were imaged by 18F-FDG-PET/CT and DW-MRI before (day 0) and after
      (day 7) a 1-week BRAF and CDK 4/6 inhibitor combination therapy (n = 12;
      dabrafenib, 20 mg/kg/d; ribociclib, 100 mg/kg/d) or placebo (n = 9). Animals were
      scanned on a small animal PET after intravenous administration of 20 MBq 18F-FDG.
      Tumor glucose uptake was calculated as the tumor-to-liver-ratio (TTL). Unenhanced
      CT data sets were subsequently acquired for anatomic coregistration. Tumor
      diffusivity was assessed by DW-MRI using the apparent diffusion coefficient
      (ADC). Anti-tumor therapy effects were assessed by ex vivo immunohistochemistry
      for validation purposes (microvascular density - CD31; tumor cell proliferation -
      Ki-67). RESULTS: Tumor glucose uptake was significantly suppressed under therapy
      (?TTLTherapy - 1.00 +/- 0.53 vs. ?TTLControl 0.85 +/- 1.21; p < 0.001). In
      addition, tumor diffusivity was significantly elevated following the BRAF and CDK
      4/6 inhibitor combination therapy (?ADCTherapy 0.12 +/- 0.14 * 10-3 mm2/s;
      ?ADCControl - 0.12 +/- 0.06 * 10-3 mm2/s; p < 0.001). Immunohistochemistry
      revealed a significant suppression of microvascular density (CD31, 147 +/- 48 vs.
      287 +/- 92; p = 0.001) and proliferation (Ki-67, 3718 +/- 998 vs. 5389 +/- 1332;
      p = 0.007) in the therapy compared to the control group. CONCLUSION: A novel BRAF
      and CDK 4/6 inhibitor combination therapy exhibited significant anti-angiogenic
      and anti-proliferative effects in experimental human melanomas, monitored by 18F
      FDG-PET/CT and DW-MRI.

PMID- 29347969
TI  - MIRO: guidelines for minimum information for the reporting of an ontology.
AB  - BACKGROUND: Creation and use of ontologies has become a mainstream activity in
      many disciplines, in particular, the biomedical domain. Ontology developers often
      disseminate information about these ontologies in peer-reviewed ontology
      description reports. There appears to be, however, a high degree of variability
      in the content of these reports. Often, important details are omitted such that
      it is difficult to gain a sufficient understanding of the ontology, its content
      and method of creation. RESULTS: We propose the Minimum Information for Reporting
      an Ontology (MIRO) guidelines as a means to facilitate a higher degree of
      completeness and consistency between ontology documentation, including published
      papers, and ultimately a higher standard of report quality. A draft of the MIRO
      guidelines was circulated for public comment in the form of a questionnaire, and
      we subsequently collected 110 responses from ontology authors, developers, users
      and reviewers. We report on the feedback of this consultation, including comments
      on each guideline, and present our analysis on the relative importance of each
      MIRO information item. These results were used to update the MIRO guidelines,
      mainly by providing more detailed operational definitions of the individual items
      and assigning degrees of importance. Based on our revised version of MIRO, we
      conducted a review of 15 recently published ontology description reports from
      three important journals in the Semantic Web and Biomedical domain and analysed
      them for compliance with the MIRO guidelines. We found that only 41.38% of the
      information items were covered by the majority of the papers (and deemed
      important by the survey respondents) and a large number of important items are
      not covered at all, like those related to testing and versioning policies.
      CONCLUSIONS: We believe that the community-reviewed MIRO guidelines can
      contribute to improving significantly the quality of ontology description reports
      and other documentation, in particular by increasing consistent reporting of
      important ontology features that are otherwise often neglected.

PMID- 29347970
TI  - A synergic effect between CYP2C19*2, CYP2C19*3 loss-of-function and CYP2C19*17
      gain-of-function alleles is associated with Clopidogrel resistance among Moroccan
      Acute Coronary Syndromes patients.
AB  - OBJECTIVE: The main objective of our study was to investigate the association of
      CYP2C19*2 and CYP2C19*3 loss-of-function and CYP2C19*17 gain-of-function variants
      of CYP2C19 gene with Clopidogrel resistance in a sample of Moroccan Acute
      Coronary Syndromes patients. RESULTS: Our results showed the existence of a
      synergic effect between the three alleles, statistically very significant, on
      Clopidogrel resistance among the treated patients (P = 0.0033). For the three
      variants of the CYP2C19 gene, the heterozygous and homozygous mutant genotypes
      were the most frequent among ACS patients (CYP2C19*2: 82.76% GA and 10.35% AA;
      CYP2C19*3: 76.67% GA and 18.33% AA; CYP2C19*17: 66.67% CT and 18.66% TT). Allelic
      frequencies were 51.73% vs 48.27% (P < 0.001); 56.67% vs 43.33% (P < 0.001); and
      52% vs 48% (P = 0.01) for the mutant and wild type alleles of the CYP2C19*2,
      CYP2C19*3 and CYP2C19*17 variants respectively. Our results support a role of
      CYP2C19 gene variants as a potential marker of Clopidogrel response.
      Understanding the functional and clinical consequences of these variants may help
      for treating patients more effectively, they could be genetically screened and
      appropriate dose adjustments could be made on the basis of their CYP2C19
      genotype.

PMID- 29347971
TI  - Detection and dissemination of Toxoplasma gondii in experimentally infected
      calves, a single test does not tell the whole story.
AB  - BACKGROUND: Although the detection of Toxoplasma gondii in bovine tissues is
      rare, beef might be an important source of human infection. The use of molecular
      techniques, such as magnetic capture qPCR (MC-qPCR), in combination with the gold
      standard method for isolating the parasite (mouse bioassay), may increase the
      sensitivity of T. gondii detection in infected cattle. The risk of transmission
      of the parasite to humans from undercooked/raw beef is not fully known and
      further knowledge about the predilection sites of T. gondii within cattle is
      needed. In the current study, six Holstein Friesian calves (Bos taurus) were
      experimentally infected with 106 T. gondii oocysts of the M4 strain and,
      following euthanasia (42 dpi), pooled tissues were tested for presence of the
      parasite by mouse bioassay and MC-qPCR. RESULTS: Toxoplasma gondii was detected
      by both MC-qPCR and mouse bioassay from distinct pools (100 g) of tissues
      comprising: liver, tongue, heart, diaphragm, semitendinosus (hindlimb),
      longissimus dorsi muscle (sirloin) and psoas major muscle (fillet). When a
      selection of individual tissues which had been used for mouse bioassay were
      examined by MC-qPCR, parasite DNA could only be detected from two animals,
      despite all calves showing seroconversion after infection. CONCLUSIONS: It is
      apparent that one individual test will not provide an answer as to whether a calf
      harbours T. gondii tissue cysts. Although the calves received a known number of
      infectious oocysts and highly sensitive methods for the detection of the parasite
      within bovine tissues were applied (mouse bioassay and MC-qPCR), the results
      confirm previous studies which report low presence of viable T. gondii in cattle
      and no clear predilection site within bovine tissues.

PMID- 29347972
TI  - Extending the utility of the WHO recommended assay for direct detection of
      enteroviruses from clinical specimen for resolving poliovirus co-infection.
AB  - OBJECTIVES: In a polio-free world there might be reduced funding for poliovirus
      surveillance. There is therefore the need to ensure that enterovirologist
      globally, especially those outside the global polio laboratory network, can
      participate in poliovirus surveillance without neglecting their enterovirus type
      of interest. To accomplish this, assays are needed that allow such active
      participation. RESULTS: In this study we describes a sensitive and specific
      utility extension of the recently recommended WHO RT-snPCR assay that enables
      independent detection of the three poliovirus types especially in cases of co
      infection. More importantly, it piggy-backs on the first round PCR product of the
      WHO recommended assay and consequently ensures that enterovirologists interested
      in nonpolio enteroviruses can continue their investigations, and contribute
      significantly and specifically to poliovirus surveillance, by using the excess of
      their first round PCR product.

PMID- 29347973
TI  - Believability of messages about preventing breast cancer and heart disease
      through physical activity.
AB  - BACKGROUND: The purpose of this research was to examine the relationships of self
      reported physical activity to involvement with messages that discuss the
      prevention of heart disease and breast cancer through physical activity, the
      explicit believability of the messages, and agreement (or disagreement) with
      specific statements about the messages or disease beliefs in general. METHODS: A
      within subjects' design was used. Participants (N = 96) read either a breast
      cancer or heart disease message first, then completed a corresponding task that
      measured agreement or disagreement and confidence in the agreement or
      disagreement that 1) physical activity 'reduces risk/does not reduce risk' of
      breast cancer or heart disease, 2) that breast cancer or heart disease is a
      'real/not real risk for me', 3) that women who get breast cancer or heart disease
      are 'like/not like me', and 4) that women who get breast cancer or heart disease
      are 'to blame/not to blame'. This task was followed by a questionnaire measuring
      message involvement and explicit believability. They then read the other disease
      messages and completed the corresponding agreement and confidence task and
      questionnaire measures. Lastly, participants completed a questionnaire measuring
      physical activity related attitudes and intentions, and demographics. RESULTS:
      There was no difference in message involvement or explicit believability of
      breast cancer compared to heart disease messages. Active participants had a
      higher confidence in their agreement that physical activity is preventive of
      heart disease compared to breast cancer. Multinomial regression models showed
      that, in addition to physical activity related attitudes and intentions,
      agreement that physical activity was preventive of heart disease and that women
      with heart disease are 'like me' were predictors of being more active compared to
      inactive. In the breast cancer model only attitudes and intentions predicted
      physical activity group. CONCLUSIONS: Active women likely internalized messages
      about heart disease prevention through physical activity, making the prevention
      messages more readily available within memory, and active women may therefore
      process such information differently. The study of how health-related beliefs are
      created and are related to perceptions of prevention messages is a rich area of
      study that may contribute to more effective health promotion.

PMID- 29347974
TI  - Correction to: Sex differences in drugs: the development of a comprehensive
      knowledge base to improve gender awareness prescribing.
AB  - CORRECTION: Unfortunately, after publication of this article [1], two errors were
      noticed. The names of Linnea Karlsson Lind and Karin Schenck-Gustafsson were
      formatted incorrectly, attributing incorrect elements to the Given and Family
      names. Further to this, a reference in Fig. 1 was missing. The line reading,
      "Fig. 1 shows the working process and each step is explained in more detail
      below" should instead read, "Fig. 1, modified from Norby et al. [2], shows the
      working process and each step is explained in more detail below".

PMID- 29347976
TI  - Intracisternal tuberculoma: a refractory type of tuberculoma indicating surgical
      intervention.
AB  - BACKGROUND: Central nervous system (CNS) tuberculoma is a rare disease with
      severe neurological deficits. This retrospective research is to review the data
      of patients diagnosed as CNS tuberculoma. Surgeries were performed in all
      patients. The clinical features especially the neurological image and the
      anatomical characters of the tuberculomas were concerned. METHODS: Totally 11
      patients diagnosed as CNS tuberculoma were admitted in Guangzhou First People's
      Hospital (7cases) and Changzheng Hospital (4 cases) during 2006-2015. The data
      including preoperative condition, neurological imaging, and surgical findings was
      collected and analyzed. RESULTS: The lesions of nine patients (9/11) were totally
      or subtotally excised and two (2/11) were partially excised. Neurological
      functions of all patients were improved after surgery without secondary
      infection. Lesions of nine (9/11) patients preoperatively progressed as a result
      of paradoxical reaction. Of the 9 patients demonstrated paradoxical progression,
      all lesions were partially or totally located at the cisterns or the subarachnoid
      space. Preoperative ATTs lasted 2 to 12 months and tuberculomas were not
      eliminated. The arachnoid was found thickened and tightly adhered to the lesions
      during surgeries. Of the 2 cases that paradoxical reaction were excluded, both
      patients (case 6, intramedullary tuberculoma; case 11, intradural extramedullary
      tuberculoma) were admitted at onset of the disease. ATTs were preoperatively
      given for 1 week as neurological deficits aggravated. The tuberculous lesions of
      CNS or other system showed no obvious change and paradoxical reaction could not
      be established in both cases. CONCLUSIONS: Exudates of tuberculosis is usually
      accumulated in the cisterns and frequently results in the paradoxical formation
      of tuberculoma. Intracisternal tuberculoma is closely related to paradoxical
      reaction and refractory to anti-tuberculosis therapy. Micro-surgical excision is
      safe and effective. Early surgical intervention may be considered in the
      diagnosis of intracisternal tuberculoma especially when paradoxical reaction
      participates in the development of tuberculoma.

PMID- 29347977
TI  - Expansion of cytochrome P450 and cathepsin genes in the generalist herbivore
      brown marmorated stink bug.
AB  - BACKGROUND: The brown marmorated stink bug (Halyomorpha halys) is an invasive
      pest in North America which causes severe economic losses on tree fruits,
      ornamentals, vegetables, and field crops. The H. halys is an extreme generalist
      and this feeding behaviour may have been a major contributor behind its
      establishment and successful adaptation in invasive habitats of North America. To
      develop an understanding into the mechanism of H. halys' generalist herbivory,
      here we specifically focused on genes putatively facilitating its adaptation on
      diverse host plants. RESULTS: We generated over 142 million reads via sequencing
      eight RNA-Seq libraries, each representing an individual H. halys adult. The de
      novo assembly contained 79,855 high quality transcripts, totalling 39,600,178
      bases. Following a comprehensive transcriptome analysis, H. halys had an expanded
      suite of cytochrome P450 and cathepsin-L genes compared to other insects.
      Detailed characterization of P450 genes from the CYP6 family, known for herbivore
      adaptation on host plants, strongly hinted towards H. halys-specific expansions
      involving gene duplications. In subsequent RT-PCR experiments, both P450 and
      cathepsin genes exhibited tissue-specific or distinct expression patterns which
      supported their principal roles of detoxification and/or digestion in a
      particular tissue. CONCLUSIONS: Our analysis into P450 and cathepsin genes in H.
      halys offers new insights into potential mechanisms for understanding generalist
      herbivory and adaptation success in invasive habitats. Additionally, the large
      scale transcriptomic resource developed here provides highly useful data for gene
      discovery; functional, population and comparative genomics as well as efforts to
      assemble and annotate the H. halys genome.

PMID- 29347975
TI  - Single low-dose primaquine for blocking transmission of Plasmodium falciparum
      malaria - a proposed model-derived age-based regimen for sub-Saharan Africa.
AB  - BACKGROUND: In 2012, the World Health Organization recommended blocking the
      transmission of Plasmodium falciparum with single low-dose primaquine (SLDPQ,
      target dose 0.25 mg base/kg body weight), without testing for glucose-6-phosphate
      dehydrogenase deficiency (G6PDd), when treating patients with uncomplicated
      falciparum malaria. We sought to develop an age-based SLDPQ regimen that would be
      suitable for sub-Saharan Africa. METHODS: Using data on the anti-infectivity
      efficacy and tolerability of primaquine (PQ), the epidemiology of anaemia, and
      the risks of PQ-induced acute haemolytic anaemia (AHA) and clinically significant
      anaemia (CSA), we prospectively defined therapeutic-dose ranges of 0.15-0.4 mg PQ
      base/kg for children aged 1-5 years and 0.15-0.5 mg PQ base/kg for individuals
      aged >=6 years (therapeutic indices 2.7 and 3.3, respectively). We chose 1.25 mg
      PQ base for infants aged 6-11 months because they have the highest rate of
      baseline anaemia and the highest risks of AHA and CSA. We modelled an
      anthropometric database of 661,979 African individuals aged >=6 months (549,127
      healthy individuals, 28,466 malaria patients and 84,386 individuals with other
      infections/illnesses) by the Box-Cox transformation power exponential and tested
      PQ doses of 1-15 mg base, selecting dosing groups based on calculated mg/kg PQ
      doses. RESULTS: From the Box-Cox transformation power exponential model, five age
      categories were selected: (i) 6-11 months (n = 39,886, 6.03%), (ii) 1-5 years (n
      = 261,036, 45.46%), (iii) 6-9 years (n = 20,770, 3.14%), (iv) 10-14 years (n =
      12,155, 1.84%) and (v) >=15 years (n = 328,132, 49.57%) to receive 1.25, 2.5, 5,
      7.5 and 15 mg PQ base for corresponding median (1st and 99th centiles) mg/kg PQ
      base of: (i) 0.16 (0.12-0.25), (ii) 0.21 (0.13-0.37), (iii) 0.25 (0.16-0.38),
      (iv) 0.26 (0.15-0.38) and (v) 0.27 (0.17-0.40). The proportions of individuals
      predicted to receive optimal therapeutic PQ doses were: 73.2 (29,180/39,886),
      93.7 (244,537/261,036), 99.6 (20,690/20,770), 99.4 (12,086/12,155) and 99.8%
      (327,620/328,132), respectively. CONCLUSIONS: We plan to test the safety of this
      age-based dosing regimen in a large randomised placebo-controlled trial
      (ISRCTN11594437) of uncomplicated falciparum malaria in G6PDd African children
      aged 0.5 - 11 years. If the regimen is safe and demonstrates adequate
      pharmacokinetics, it should be used to support malaria elimination.

PMID- 29347979
TI  - Altered environmental light drives retinal change in the Atlantic Tarpon
      (Megalops atlanticus) over timescales relevant to marine environmental
      disturbance.
AB  - BACKGROUND: For many fish species, retinal function changes between life history
      stages as part of an encoded developmental program. Retinal change is also known
      to exhibit plasticity because retinal form and function can be influenced by
      light exposure over the course of development. Aside from studies of gene
      expression, it remains largely unknown whether retinal plasticity can provide
      functional responses to short-term changes in environmental light quality. The
      aim of this study was to determine whether the structure and function of the fish
      retina can change in response to altered light intensity and spectrum-not over
      the course of a developmental regime, but over shorter time periods relevant to
      marine habitat disturbance. RESULTS: The effects of light environment on
      sensitivity of the retina, as well as on cone photoreceptor distribution were
      examined in the Atlantic tarpon (Megalops atlanticus) on 2- and 4-month
      timescales. In a spectral experiment, juvenile M. atlanticus were placed in
      either 'red' or 'blue' light conditions (with near identical irradiance), and in
      an intensity experiment, juveniles were placed in either 'bright' or 'dim' light
      conditions (with near identical spectra). Analysis of the retina by
      electroretinography and anti-opsin immunofluorescence revealed that relative to
      fish held in the blue condition, those in the red condition exhibited longer
      wavelength peak sensitivity and greater abundance of long-wavelength-sensitive
      (LWS) cone photoreceptors over time. Following pre-test dark adaption of the
      retina, fish held in the dim light required less irradiance to produce a standard
      retinal response than fish held in bright light, developing a greater sensitivity
      to white light over time. CONCLUSIONS: The results show that structure and
      function of the M. atlanticus retina can rapidly adjust to changes in
      environmental light within a given developmental stage, and that such changes are
      dependent on light quality and the length of exposure. These findings suggest
      that the fish retina may be resilient to disturbances in environmental light,
      using retinal plasticity to compensate for changes in light quality over short
      timescales.

PMID- 29347978
TI  - Uninvestigated dyspepsia and associated factors of patients with gastrointestinal
      disorders in Dessie Referral Hospital, Northeast Ethiopia.
AB  - BACKGROUND: Dyspepsia is a common problem in the community and clinical practice
      with symptom(s) considered arising from the gastroduodenal region. Dyspepsia
      burden and associated factors vary from country to country. The aim of this study
      was to determine the prevalence of uninvestigated dyspepsia (UD) using Rome III
      criteria, associated risk factors and self-reported dyspepsia symptoms'
      correlation with H. pylori infection. METHODS: A cross-sectional study was
      conducted among randomly selected 318 out patients with gastrointestinal
      complaints during the period from September 1 to December 30, 2015. All patients
      completed a questionnaire for collecting data regarding sociodemographic,
      lifestyle and functional gastrointestinal disorders. Diagnosis of dyspepsia was
      made according to the Rome III criteria. H. pylori infection was assessed using
      stool antigen test. SPSS version 20.0 statistical software package was used for
      data analysis. RESULTS: From a total of 318 patients, 48.4% had UD according to
      Rome III criteria; with 42.1% symptoms of epigastric pain/burning, 26.1%
      postprandial fullness and 22.6% early satiation. Epigastric pain/burning (AOR =
      1.92, 95% CI 1.07-3.43), early satiation (AOR = 2.68, 95% CI 1.38-5.20) and
      belching (AOR = 4.7, 95% CI 1.54-14.40) were significantly correlated with H.
      pylori infection. H. pylori infection (AOR = 4.33, 95% CI 2.41-7.76) and
      aspirin/NSAIDs consumption (AOR = 5.29, 95% CI 2.82-9.93) were independent risk
      factors for UD. However, consumption of raw fruits/ vegetables at least once a
      week (AOR = 0.48, 95% CI 0.24-0.98) and taking two or more cups of tea a day (AOR
      = 0.339, 95% CI 0.17-0.70) were inversely associated with UD. CONCLUSIONS: UD is
      highly prevalent among adults with gastrointestinal complaints. H. pylori
      infection is significantly associated with UD and correlates with its symptoms.
      Individuals with epigastric pain/burning, early satiation and belching should be
      primary focus of H. pylori infection diagnosis and treatment. The role of
      consumption of tea, raw fruits and vegetables on dyspepsia needs further large
      scale study.

PMID- 29347980
TI  - Semiprone position is superior to supine position for paediatric endotracheal
      intubation during massive regurgitation, a randomized crossover simulation trial.
AB  - BACKGROUND: Endotracheal intubation of patients with massive regurgitation
      represents a challenge in emergency airway management. Gastric contents tend to
      block suction catheters, and few treatment alternatives exist. Based on a
      technique that was successfully applied in our district, we wanted to examine if
      endotracheal intubation would be easier and quicker to perform when the patient
      is turned over to a semiprone position, as compared to the supine position.
      METHODS: In a randomized crossover simulation trial, a child manikin with on
      going regurgitation was intubated both in the supine and semiprone positions.
      Endpoints were experienced difficulty with the procedure and time to intubation,
      as well as visually confirmed intubation and first-pass success rate. RESULTS:
      Intubation in the semiprone position was significantly easier and faster compared
      to the supine position; the median experienced difficulty on a visual analogue
      scale was 27 and 65, respectively (p = 0.004), and the median time to intubation
      was 26 and 45 s, respectively (p = 0.001). There were no significant differences
      in frequency of visually confirmed intubation (16 and 18, p = 0.490) of first
      pass success rate (17 and 18, p = 1.000). CONCLUSION: In this experiment,
      endotracheal intubation during massive regurgitation with the patient in the
      semiprone position was significantly easier and quicker to perform than in the
      supine position. Endotracheal intubation in the semiprone position can provide a
      quick rescue method in situations where airway management is hindered by massive
      regurgitation, and it represents a possible supplement to current airway
      management training.

PMID- 29347981
TI  - Radiation-induced pulmonary gene expression changes are attenuated by the CTGF
      antibody Pamrevlumab.
AB  - BACKGROUND: Fibrosis is a delayed side effect of radiation therapy (RT).
      Connective tissue growth factor (CTGF) promotes the development of fibrosis in
      multiple settings, including pulmonary radiation injury. METHODS: To better
      understand the cellular interactions involved in RT-induced lung injury and the
      role of CTGF in these responses, microarray expression profiling was performed on
      lungs of irradiated and non-irradiated mice, including mice treated with the anti
      CTGF antibody pamrevlumab (FG-3019). Between group comparisons (Welch's t-tests)
      and principal components analyses were performed in Genespring. RESULTS: At the
      mRNA level, the ability of pamrevlumab to prolong survival and ameliorate RT
      induced radiologic, histologic and functional lung deficits was correlated with
      the reversal of a clear enrichment in mast cell, macrophage, dendritic cell and
      mesenchymal gene signatures. Cytokine, growth factor and matrix remodeling genes
      that are likely to contribute to RT pneumonitis and fibrosis were elevated by RT
      and attenuated by pamrevlumab, and likely contribute to the cross-talk between
      enriched cell-types in injured lung. CONCLUSIONS: CTGF inhibition had a
      normalizing effect on select cell-types, including immune cells not typically
      regarded as being regulated by CTGF. These results suggest that interactions
      between RT-recruited cell-types are critical to maintaining the injured state;
      that CTGF plays a key role in this process; and that pamrevlumab can ameliorate
      RT-induced lung injury in mice and may provide therapeutic benefit in other
      immune and fibrotic disorders.

PMID- 29347982
TI  - Emergency department hyperoxia is associated with increased mortality in
      mechanically ventilated patients: a cohort study.
AB  - BACKGROUND: Providing supplemental oxygen is fundamental in the management of
      mechanically ventilated patients. Increasing amounts of data show worse clinical
      outcomes associated with hyperoxia. However, these previous data in the
      critically ill have not focused on outcomes associated with brief hyperoxia
      exposure immediately after endotracheal intubation. Therefore, the objectives of
      this study were to evaluate the impact of isolated early hyperoxia exposure in
      the emergency department (ED) on clinical outcomes among mechanically ventilated
      patients with subsequent normoxia in the intensive care unit (ICU). METHODS: This
      was an observational cohort study conducted in the ED and ICUs of an academic
      center in the USA. Mechanically ventilated normoxic (partial pressure of arterial
      oxygen (PaO2) 60-120 mm Hg) ICU patients with mechanical ventilation initiated in
      the ED were studied. The cohort was categorized into three oxygen exposure groups
      based on PaO2 values obtained after ED intubation: hypoxia, normoxia, and
      hyperoxia (defined as PaO2 < 60 mmHg, PaO2 60-120 mm Hg, and PaO2 > 120 mm Hg,
      respectively, based on previous literature). RESULTS: A total of 688 patients
      were included. ED normoxia occurred in 350 (50.9%) patients, and 300 (43.6%) had
      exposure to ED hyperoxia. The ED hyperoxia group had a median (IQR) ED PaO2 of
      189 mm Hg (146-249), compared to an ED PaO2 of 88 mm Hg (76-101) in the normoxia
      group, P < 0.001. Patients with ED hyperoxia had greater hospital mortality
      (29.7%), when compared to those with normoxia (19.4%) and hypoxia (13.2%). After
      multivariable logistic regression analysis, ED hyperoxia was an independent
      predictor of hospital mortality (adjusted OR 1.95 (1.34-2.85)). CONCLUSIONS: ED
      exposure to hyperoxia is common and associated with increased mortality in
      mechanically ventilated patients achieving normoxia after admission. This
      suggests that hyperoxia in the immediate post-intubation period could be
      particularly injurious, and targeting normoxia from initiation of mechanical
      ventilation may improve outcome.

PMID- 29347983
TI  - Experiences of an internet-based support and coaching model for adolescents and
      young adults with ADHD and autism spectrum disorder -a qualitative study.
AB  - BACKGROUND: There is a great demand for non-medical treatment and support
      targeting the needs of adolescents and young adults with autism spectrum disorder
      (ASD) and attention-deficit/hyperactivity disorder (ADHD). There is also a lack
      of qualitative studies providing in-depth insight into these individuals' own
      experiences within this area. The current study aimed to explore how adolescents
      and young adults with ADHD, ASD or both experienced taking part in an internet
      based support and coaching intervention. METHODS: Sixteen participants with ASD,
      ADHD or both who had participated in an 8-week internet-based support and
      coaching model, were interviewed using semi-structured interviews. Data was
      analyzed using qualitative content analysis. RESULTS: Analysis yielded three
      themes; Deciding to participate, Taking part in the coaching process and The
      significance of format. Various motives for joining were expressed by
      participants, such as viewing the technology as familiar and appealing and
      expecting it to be better suited to their situation. There was also a previously
      unfulfilled need for support among participants. In deciding to take part in the
      intervention the coaches' competence and knowledge were considered essential,
      often in the light of previously negative experiences. Taking part in the
      coaching process meant feeling reassured by having someone to turn to in view of
      shared obstacles to seeking and receiving help. The support was used for talking
      through and receiving advice on matters related to their diagnosis. Findings
      further revealed appreciation for aspects relating to the format such as
      communicating through the written word, being in one's own home and an experience
      of immediacy. Some disadvantages were voiced including incomplete personal
      interaction and failing technology. There were also suggestions for greater
      flexibility. CONCLUSIONS: The in-depth qualitative data obtained from this study
      suggest that the current model of support and the internet-based format have
      specific qualities that could play an important role in the support of
      adolescents and young adults with ADHD and ASD. Although not a replacement for
      face-to-face interaction, it could be a promising complement or alternative to
      other support and treatment options. TRIAL REGISTRATION: "Internet-based Support
      for Young People with ADHD and Autism - a Controlled Study" retrospectively
      registered in www.clinicaltrials.gov ( ClinicalTrials.gov Identifier: NCT02300597
      ) at 2014-11-10.

PMID- 29347984
TI  - The effects of state rules on opioid prescribing in Indiana.
AB  - BACKGROUND: Prescription opioids have been linked to over half of the 28,000
      opioid overdose deaths in 2014. High rates of prescription opioid non-medical use
      have continued despite nearly all states implementing large-scale prescription
      drug monitoring programs (PDMP), which points to the need to examine the impact
      of state PDMP's on curbing inappropriate opioid prescribing. In the short-term,
      PDMPs have been associated with short-term prescribing declines. Yet little is
      known about how such policies differentially impact patient subgroups or are
      interpreted by prescribing providers. Our objective was to compare volumes of
      prescribed opioids before and after Indiana implemented opioid prescribing
      emergency rules and stratify the changes in opioid prescribing by patient and
      provider subgroups. METHODS: An interrupted time series analysis was conducted
      using data obtained from the Indiana PDMP. Prescription level data was merged
      with census data to characterize patient socioeconomic status. Analyses were
      stratified by patients' gender, age, opioid dosage, and payer. The primary
      outcome indicator was the total morphine equivalent dose (MED) of dispensed
      opioids per day in the state of Indiana. Also considered were number of unique
      patients, unique providers, and prescriptions; MED per transaction and per day;
      and number of days supplied. RESULTS: After controlling for time trends, we found
      that total MED for opioids decreased after implementing the new emergency rules,
      differing by patient gender, age, and payer. The effect was larger for males than
      females and almost 10 times larger for 0-20 year olds as compared to the 60+ age
      range. Medicare and Medicaid patients experienced more decline in prescribing
      than patients with private insurance. Patients with prescriptions paid for by
      workers' comp experienced the most significant decline. The emergency rules were
      associated with decline in both the number of prescribers and the number of day
      supply. CONCLUSIONS: Although the Indiana opioid prescribing emergency rules
      impacted statewide prescribing behavior across all individual patient and
      provider characteristics, the emergency rules' effect was not consistent across
      patient characteristics. Further studies are needed to assess how individual
      patient characteristics influence the interpretation and application of state
      policies on opioid prescribing.

PMID- 29347985
TI  - Seasonal and inter-annual variation of malaria parasite detection in wild
      chimpanzees.
AB  - BACKGROUND: Cross-sectional surveys of chimpanzee (Pan troglodytes) communities
      across sub-Saharan Africa show large geographical variation in malaria parasite
      (Plasmodium spp.) prevalence. The drivers leading to this apparent spatial
      heterogeneity may also be temporally dynamic but data on prevalence variation
      over time are missing for wild great apes. This study aims to fill this
      fundamental gap. METHODS: Some 681 faecal samples were collected from 48
      individuals of a group of habituated chimpanzees (Tai National Park, Cote
      d'Ivoire) across four non-consecutive sampling periods between 2005 and 2015.
      RESULTS: Overall, 89 samples (13%) were PCR-positive for malaria parasite DNA.
      The proportion of positive samples ranged from 0 to 43% per month and 4 to 27%
      per sampling period. Generalized Linear Mixed Models detected significant
      seasonal and inter-annual variation, with seasonal increases during the wet
      seasons and apparently stochastic inter-annual variation. Younger individuals
      were also significantly more likely to test positive. CONCLUSIONS: These results
      highlight strong temporal fluctuations of malaria parasite detection rates in
      wild chimpanzees. They suggest that the identification of other drivers of
      malaria parasite prevalence will require longitudinal approaches and caution
      against purely cross-sectional studies, which may oversimplify the dynamics of
      this host-parasite system.

PMID- 29347986
TI  - Untapped aspects of mass media campaigns for changing health behaviour towards
      non-communicable diseases in Bangladesh.
AB  - In recent years, non-communicable diseases (NCDs) have become epidemic in
      Bangladesh. Behaviour changing interventions are key to prevention and management
      of NCDs. A great majority of people in Bangladesh have low health literacy, are
      less receptive to health information, and are unlikely to embrace positive health
      behaviours. Mass media campaigns can play a pivotal role in changing health
      behaviours of the population. This review pinpoints the role of mass media
      campaigns for NCDs and the challenges along it, whilst stressing on NCD
      preventive programmes (with the examples from different countries) to change
      health behaviours in Bangladesh. Future research should underpin the use of
      innovative technologies and mobile phones, which might be a prospective option
      for NCD prevention and management in Bangladesh.

PMID- 29347987
TI  - Determinants of long-term outcome in ICU survivors: results from the FROG-ICU
      study.
AB  - BACKGROUND: Intensive care unit (ICU) survivors have reduced long-term survival
      compared to the general population. Identifying parameters at ICU discharge that
      are associated with poor long-term outcomes may prove useful in targeting an at
      risk population. The main objective of the study was to identify clinical and
      biological determinants of death in the year following ICU discharge. METHODS:
      FROG-ICU was a prospective, observational, multicenter cohort study of ICU
      survivors followed 1 year after discharge, including 21 medical, surgical or
      mixed ICUs in France and Belgium. All consecutive patients admitted to intensive
      care with a requirement for invasive mechanical ventilation and/or vasoactive
      drug support for more than 24 h following ICU admission and discharged from ICU
      were included. The main outcome measure was all-cause mortality at 1 year after
      ICU discharge. Clinical and biological parameters on ICU discharge were measured,
      including the circulating cardiovascular biomarkers N-terminal pro-B type
      natriuretic peptide, high-sensitive troponin I, bioactive-adrenomedullin and
      soluble-ST2. Socioeconomic status was assessed using a validated deprivation
      index (FDep). RESULTS: Of 1570 patients discharged alive from the ICU, 333 (21%)
      died over the following year. Multivariable analysis identified age, comorbidity,
      red blood cell transfusion, ICU length of stay and abnormalities in common
      clinical factors at the time of ICU discharge (low systolic blood pressure,
      temperature, total protein, platelet and white cell count) as independent factors
      associated with 1-year mortality. Elevated biomarkers of cardiac and vascular
      failure independently associated with 1-year death when they are added to
      multivariable model, with an almost 3-fold increase in the risk of death when
      combined (adjusted odds ratio 2.84 (95% confidence interval 1.73-4.65), p <
      0.001). CONCLUSIONS: The FROG-ICU study identified, at the time of ICU discharge,
      potentially actionable clinical and biological factors associated with poor long
      term outcome after ICU discharge. Those factors may guide discharge planning and
      directed interventions. TRIAL REGISTRATION: ClinicalTrials.gov NCT01367093 .
      Registered on 6 June 2011.

PMID- 29347988
TI  - Efficacy of melatonin for sleep disturbance following traumatic brain injury: a
      randomised controlled trial.
AB  - BACKGROUND: The study aimed to determine the efficacy of melatonin
      supplementation for sleep disturbances in patients with traumatic brain injury
      (TBI). METHODS: This is a randomised double-blind placebo-controlled two-period
      two-treatment (melatonin and placebo) crossover study. Outpatients were recruited
      from Epworth and Austin Hospitals Melbourne, Australia. They had mild to severe
      TBI (n = 33) reporting sleep disturbances post-injury (mean age 37 years,
      standard deviation 11 years; 67% men). They were given prolonged-release
      melatonin formulation (2 mg; Circadin(r)) and placebo capsules for 4 weeks each
      in a counterbalanced fashion separated by a 48-hour washout period. Treatment was
      taken nightly 2 hours before bedtime. Serious adverse events and side-effects
      were monitored. RESULTS: Melatonin supplementation significantly reduced global
      Pittsburgh Sleep Quality Index scores relative to placebo, indicating improved
      sleep quality [melatonin 7.68 vs. placebo 9.47, original score units; difference 
      1.79; 95% confidence interval (CI), -2.70 to -0.88; p <= 0.0001]. Melatonin had
      no effect on sleep onset latency (melatonin 1.37 vs. placebo 1.42, log units;
      difference -0.05; 95% CI, -0.14 to 0.03; p = 0.23). With respect to the secondary
      outcomes, melatonin supplementation increased sleep efficiency on actigraphy, and
      vitality and mental health on the SF-36 v1 questionnaire (p <= 0.05 for each).
      Melatonin decreased anxiety on the Hospital Anxiety Depression Scale and fatigue
      on the Fatigue Severity Scale (p <= 0.05 for both), but had no significant effect
      on daytime sleepiness on the Epworth Sleepiness Scale (p = 0.15). No serious
      adverse events were reported. CONCLUSIONS: Melatonin supplementation over a 4
      week period is effective and safe in improving subjective sleep quality as well
      as some aspects of objective sleep quality in patients with TBI. TRIAL
      REGISTRATION: Identifier: 12611000734965; Prospectively registered on 13 July
      2011.

PMID- 29347989
TI  - Balo's concentric sclerosis is immunologically distinct from multiple sclerosis:
      results from retrospective analysis of almost 150 lumbar punctures.
AB  - BACKGROUND: Balo's concentric sclerosis (BCS) is a rare inflammatory
      demyelinating disorder of the central nervous system characterised by concentric
      layers of demyelination. It is unclear whether BCS is a variant of multiple
      sclerosis (MS) or a disease entity in its own right. OBJECTIVE: To compare the
      cerebrospinal fluid (CSF) features of BCS to those of MS. METHODS: Retrospective
      analysis of the CSF profile of all patients with BCS reported in the medical
      literature between 1980 and 2017. RESULTS: In total, the results of 146 lumbar
      punctures (LP) in 132 patients were analysed. The most striking finding was a
      lack of CSF-restricted oligoclonal bands (OCB) in 66% (56/85) of all LP in the
      total BCS group, in 74% (14/19) in the subgroup of patients with both MRI and
      histological evidence for BCS, and in 82% (18/22) in the subgroup of patients
      with highest radiological confidence (high MRI quality, >= 3 layers of
      demyelination). OCB disappeared in 1/2 initially OCB-positive patients. These
      findings are in stark contrast to MS, in which OCB are present in >= 95% of
      patients and are thought to remain stably detectable over the entire course of
      disease (p < 0.000001). OCB frequency was low both in 'historic' patients (1980
      2009; 37%) and in more recent patients (2010-2017; 31%). OCB-positive and OCB
      negative patients did not differ significantly with regard to age, sex, disease
      duration, number of Balo-like lesions on MRI, number of relapses, treatment or
      final outcome. In accordance with the high rate of OCB negativity, Link's IgG
      index was negative in 63% of all tested samples (p < 0.000001 vs. MS). CSF
      pleocytosis was present in 28% (27/96; p < 0.000001 vs. MS) and elevated CSF
      total protein levels in 41% (31/76) of samples. CONCLUSION: OCB and IgG index
      frequencies in BCS are much more similar to those reported in neuromyelitis
      optica or myelin oligodendrocyte glycoprotein antibody-associated
      encephalomyelitis than to those in MS. Our findings suggest that in most cases
      BCS-like lesions denote the presence of a disease entity immunologically distinct
      from MS. In addition, we provide data on the demographics, clinical course and
      radiological features of BCS based on the largest cohort analysed to date.

PMID- 29347990
TI  - Establishment of an in vitro chicken epithelial cell line model to investigate
      Eimeria tenella gamete development.
AB  - BACKGROUND: Eimeria tenella infection leads to acute intestinal disorders
      responsible for important economic losses in poultry farming worldwide. The life
      cycle of E. tenella is monoxenous with the chicken as the exclusive host;
      infection occurs in caecal epithelial cells. However, in vitro, the complete life
      cycle of the parasite has only been propagated successfully in primary chicken
      kidney cells, which comprise undefined mixed cell populations; no cell line model
      has been able to consistently support the development of the sexual stages of the
      parasite. We therefore sought to develop a new model to study E. tenella
      gametogony in vitro using a recently characterised chicken cell line (CLEC-213)
      exhibiting an epithelial cell phenotype. METHODS: CLEC-213 were infected with
      sporozoites from a precocious strain or with second generation merozoites
      (merozoites II) from wild type strains. Sexual stages of the parasite were
      determined both at the gene and protein levels. RESULTS: To our knowledge, we
      show for the first time in CLEC-213, that sporozoites from a precocious strain of
      E. tenella were able to develop to gametes, as verified by measuring gene
      expression and by using antibodies to a microgamete-specific protein (EtFOA1:
      flagellar outer arm protein 1) and a macrogamete-specific protein (EtGAM-56), but
      oocysts were not observed. However, both gametes and oocysts were observed when
      cells were infected with merozoites II from wild type strains, demonstrating that
      completion of the final steps of the parasite cycle is possible in CLEC-213
      cells. CONCLUSION: The epithelial cell line CLEC-213 constitutes a useful avian
      tool for studying Eimeria epithelial cell interactions and the effect of drugs on
      E. tenella invasion, merogony and gametogony.

PMID- 29347992
TI  - Anatomical relation between S1 sacroiliac screws' entrance points and superior
      gluteal artery.
AB  - BACKGROUND: To conduct radiologic anatomical study on the relation between S1
      sacroiliac screws' entry points and the route of the pelvic outer superior
      gluteal artery branches with the aim to provide the anatomical basis and
      technical reference for the avoidance of damage to the superior gluteal artery
      during the horizontal sacroiliac screw placement. METHODS: Superior gluteal
      artery CTA (CT angiography) vascular imaging of 74 healthy adults (37 women and
      37 men) was done with 128-slice spiral CT (computed tomography). The CT attendant
      measuring software was used to portray the "safe bony entrance area" (hereinafter
      referred to as "Safe Area") of the S1 segment in the standard lateral pelvic view
      of three-dimensional reconstruction. The anatomical relation between S1
      sacroiliac screws' Safe Area and the pelvic outer superior gluteal artery
      branches was observed and recorded. The number of cases in which artery branches
      intersected the Safe Area was counted. The cases in which superior gluteal artery
      branches disjointed from the Safe Area were identified, and the shortest distance
      between the Safe Area and the superior gluteal artery branch closest to the Safe
      Area was measured. RESULTS: Three cases out of the 74 sample cases were excluded
      from this study as they were found to have no bony space for horizontal screw
      placement in S1 segment. Among the remaining 71 sample cases, there are 32 cases
      (45.1%) where the deep superior branch of superior gluteal artery passes through
      the Safe Area of S1 entrance point. There was no distinguishing feature and rule
      on how the deep superior branches and the Safe Area overlapped. In the 39 cases
      in which superior gluteal artery branches disjointed from the Safe Area, the deep
      superior branches of superior gluteal artery were the branches closest to the
      Safe Area and the part of the branch closest to the Safe Area was located in
      front of the widest part of the Safe Area. The shortest distance between the deep
      superior branch and the Safe Area is 0.86 +/- 0.84 cm. CONCLUSION: There is a
      high risk of accidental injury of the deep superior branches of superior gluteal
      artery in the process of S1 sacroiliac screw placement. Even if the entry points
      are located in the safe bony entrance area, the absolute secure placement cannot
      be assured. We suggest that great attention should be paid to make thorough
      preoperative plans.

PMID- 29347991
TI  - The benefits and tolerance of exercise in myasthenia gravis (MGEX): study
      protocol for a randomised controlled trial.
AB  - BACKGROUND: Research exploring the effects of physical exercise in auto-immune
      myasthenia gravis (MG) is scarce. The few existing studies present methodological
      shortcomings limiting the conclusions and generalisability of results. It is
      hypothesised that exercise could have positive physical, psychological as well as
      immunomodulatory effects and may be a beneficial addition to current
      pharmacological management of this chronic disease. The aim of this study is to
      evaluate the benefits on perceived quality of life (QOL) and physical fitness of
      a home-based physical exercise program compared to usual care, for patients with
      stabilised, generalised auto-immune MG. METHODS: MGEX is a multi-centre,
      interventional, randomised, single-blind, two-arm parallel group, controlled
      trial. Forty-two patients will be recruited, aged 18-70 years. Following a three
      month observation period, patients will be randomised into a control or
      experimental group. The experimental group will undertake a 40-min home-based
      physical exercise program using a rowing machine, three times a week for three
      months, as an add-on to usual care. The control group will receive usual care
      with no additional treatment. All patients will be followed up for a further
      three months. The primary outcome is the mean change in MGQOL-15-F score between
      three and six months (i.e. pre-intervention and immediately post-intervention
      periods). The MGQOL-15-F is an MG-specific patient-reported QOL questionnaire.
      Secondary outcomes include the evaluation of deficits and functional limitations
      via MG-specific clinical scores (Myasthenia Muscle Score and MG-Activities of
      Daily Living scale), muscle force and fatigue, respiratory function, free-living
      physical activity as well as evaluations of anxiety, depression, self-esteem and
      overall QOL with the WHO-QOL BREF questionnaire. Exercise workload will be
      assessed as well as multiple safety measures (ECG, biological markers, medication
      type and dosage and any disease exacerbation or crisis). DISCUSSION: This is the
      largest randomised controlled trial to date evaluating the benefits and tolerance
      of physical exercise in this patient population. The comprehensive evaluations
      using standardised outcome measures should provide much awaited information for
      both patients and the scientific community. This study is ongoing. TRIAL
      REGISTRATION: ClinicalTrials.gov, NCT02066519 . Registered on 13 January 2014.

PMID- 29347993
TI  - Updated efficacy of avelumab in patients with previously treated metastatic
      Merkel cell carcinoma after >=1 year of follow-up: JAVELIN Merkel 200, a phase 2
      clinical trial.
AB  - BACKGROUND: Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer
      associated with poor survival outcomes in patients with distant metastatic
      disease (mMCC). In an initial analysis from JAVELIN Merkel 200, a phase 2,
      prospective, open-label, single-arm trial in mMCC, avelumab-a human anti
      programmed death-ligand 1 (PD-L1) monoclonal antibody-showed promising efficacy
      and a safety profile that was generally manageable and tolerable. Here, we report
      the efficacy of avelumab after >=1 year of follow-up in patients with distant
      mMCC that had progressed following prior chemotherapy for metastatic disease.
      PATIENTS AND METHODS: Patients received avelumab 10 mg/kg by 1-h intravenous
      infusion every 2 weeks until confirmed disease progression, unacceptable
      toxicity, or withdrawal. The primary endpoint was best overall response.
      Secondary endpoints included duration of response (DOR), progression-free
      survival (PFS), and overall survival (OS). RESULTS: Patients (N = 88) were
      followed for a minimum of 12 months. The confirmed objective response rate was
      33.0% (95% CI, 23.3%-43.8%; complete response: 11.4%). An estimated 74% of
      responses lasted >=1 year, and 72.4% of responses were ongoing at data cutoff.
      Responses were durable, with the median DOR not yet reached (95% CI, 18.0 months
      not estimable), and PFS was prolonged; 1-year PFS and OS rates were 30% (95% CI,
      21%-41%) and 52% (95% CI, 41%-62%), respectively. Median OS was 12.9 months (95%
      CI, 7.5-not estimable). Subgroup analyses suggested a higher probability of
      response in patients receiving fewer prior lines of systemic therapy, with a
      lower baseline disease burden, and with PD-L1-positive tumors; however, durable
      responses occurred irrespective of baseline factors, including tumor Merkel cell
      polyomavirus status. CONCLUSIONS: With longer follow-up, avelumab continues to
      show durable responses and promising survival outcomes in patients with distant
      mMCC whose disease had progressed after chemotherapy. TRIAL REGISTRATION:
      Clinicaltrials.gov identifier: NCT02155647.

PMID- 29347995
TI  - Index of the human papillomavirus (HPV) vaccine industry clinical study
      programmes and non-industry funded studies: a necessary basis to address
      reporting bias in a systematic review.
AB  - BACKGROUND: Unabridged access to drug industry and regulatory trial registers and
      data reduces reporting bias in systematic reviews and may provide a complete
      index of a drug's clinical study programme. Currently, there is no public index
      of the human papillomavirus (HPV) vaccine industry study programmes or a public
      index of non-industry funded studies. METHODS: By cross-verification via study
      programme enquiries to the HPV vaccine manufacturers and regulators and searches
      of trial registers and journal publication databases, we indexed clinical HPV
      vaccine studies as a basis to address reporting bias in a systematic review of
      clinical study reports. RESULTS: We indexed 206 clinical studies: 145 industry
      and 61 non-industry funded studies. One of the four HPV vaccine manufacturers
      (GlaxoSmithKline) provided information on its study programme. Most studies were
      cross-verified from two or more sources (160/206, 78%) and listed on regulatory
      or industry trial registers or journal publication databases (195/206, 95%)-in
      particular, on ClinicalTrials.gov (176/195, 90%). However, study results were
      only posted for about half of the completed studies on ClinicalTrials.gov
      (71/147, 48%). Two thirds of the industry studies had a study programme ID,
      manufacturer specific ID, and national clinical trial (NCT) ID (91/145, 63%).
      Journal publications were available in journal publication databases (the
      Cochrane Collaboration's Central Register of Controlled Trials, Google Scholar
      and PubMed) for two thirds of the completed studies (92/149, 62%). CONCLUSION: We
      believe we came close to indexing complete HPV vaccine study programmes, but only
      one of the four manufacturers provided information for our index and a fifth of
      the index could not be cross-verified. However, we indexed larger study
      programmes than those listed by major regulators (i.e., the EMA and FDA that
      based their HPV vaccine approvals on only half of the available trials). To
      reduce reporting bias in systematic reviews, we advocate the registration and
      publication of all studies and data in the public domain.

PMID- 29347994
TI  - The apelinergic system as an alternative to catecholamines in low-output septic
      shock.
AB  - Catecholamines, in concert with fluid resuscitation, have long been recommended
      in the management of septic shock. However, not all patients respond positively
      and controversy surrounding the efficacy-to-safety profile of catecholamines has
      emerged, trending toward decatecholaminization. Contextually, it is time to re
      examine the "maintaining blood pressure" paradigm by identifying safer and life
      saving alternatives. We put in perspective the emerging and growing knowledge on
      a promising alternative avenue: the apelinergic system. This target exhibits
      invaluable pleiotropic properties, including inodilator activity, cardio-renal
      protection, and control of fluid homeostasis. Taken together, its effects are
      expected to be greatly beneficial for patients in septic shock.

PMID- 29347997
TI  - OpenBiodiv-O: ontology of the OpenBiodiv knowledge management system.
AB  - BACKGROUND: The biodiversity domain, and in particular biological taxonomy, is
      moving in the direction of semantization of its research outputs. The present
      work introduces OpenBiodiv-O, the ontology that serves as the basis of the
      OpenBiodiv Knowledge Management System. Our intent is to provide an ontology that
      fills the gaps between ontologies for biodiversity resources, such as DarwinCore
      based ontologies, and semantic publishing ontologies, such as the SPAR
      Ontologies. We bridge this gap by providing an ontology focusing on biological
      taxonomy. RESULTS: OpenBiodiv-O introduces classes, properties, and axioms in the
      domains of scholarly biodiversity publishing and biological taxonomy and aligns
      them with several important domain ontologies (FaBiO, DoCO, DwC, Darwin-SW,
      NOMEN, ENVO). By doing so, it bridges the ontological gap across scholarly
      biodiversity publishing and biological taxonomy and allows for the creation of a
      Linked Open Dataset (LOD) of biodiversity information (a biodiversity knowledge
      graph) and enables the creation of the OpenBiodiv Knowledge Management System. A
      key feature of the ontology is that it is an ontology of the scientific process
      of biological taxonomy and not of any particular state of knowledge. This feature
      allows it to express a multiplicity of scientific opinions. The resulting
      OpenBiodiv knowledge system may gain a high level of trust in the scientific
      community as it does not force a scientific opinion on its users (e.g. practicing
      taxonomists, library researchers, etc.), but rather provides the tools for
      experts to encode different views as science progresses. CONCLUSIONS: OpenBiodiv
      O provides a conceptual model of the structure of a biodiversity publication and
      the development of related taxonomic concepts. It also serves as the basis for
      the OpenBiodiv Knowledge Management System.

PMID- 29347998
TI  - Radiation exposure in transcatheter patent ductus arteriosus closure: time to
      tune?
AB  - OBJECTIVES: The aims of this study were to describe radiation level at our
      institution during transcatheter patent ductus arteriosus occlusion and to
      evaluate the components contributing to radiation exposure. BACKGROUND:
      Transcatheter occlusion relying on X-ray imaging has become the treatment of
      choice for patients with patent ductus arteriosus. Interventionists now work hard
      to minimise radiation exposure in order to reduce risk of induced cancers.
      METHODS: We retrospectively reviewed all consecutive children who underwent
      transcatheter closure of patent ductus arteriosus from January 2012 to January
      2016. Clinical data, anatomical characteristics, and catheterisation procedure
      parameters were reported. Radiation doses were analysed for the following
      variables: total air kerma, mGy; dose area product, Gy.cm2; dose area product per
      body weight, Gy.cm2/kg; and total fluoroscopic time. RESULTS: A total of 324
      patients were included (median age=1.51 [Q1-Q3: 0.62-4.23] years; weight=10.3
      [6.7-17.0] kg). In all, 322/324 (99.4%) procedures were successful. The median
      radiation doses were as follows: total air kerma: 26 (14.5-49.3) mGy; dose area
      product: 1.01 (0.56-2.24) Gy.cm2; dose area product/kg: 0.106 (0.061-0.185)
      Gy.cm2/kg; and fluoroscopic time: 2.8 (2-4) min. In multivariate analysis, a
      weight >10 kg, a ductus arteriosus width <2 mm, complications during the
      procedure, and a high frame rate (15 frames/second) were risk factors for an
      increased exposure. CONCLUSION: Lower doses of radiation can be achieved with
      subsequent recommendations: technical improvement, frame rate reduction,
      avoidance of biplane cineangiograms, use of stored fluoroscopy as much as
      possible, and limitation of fluoroscopic time. A greater use of echocardiography
      might even lessen the exposure.

PMID- 29347999
TI  - Whether you are a virus or a learned society-based virology journal, evolution is
      critical for success!

PMID- 29347996
TI  - The Apathy in Dementia Methylphenidate Trial 2 (ADMET 2): study protocol for a
      randomized controlled trial.
AB  - BACKGROUND: Alzheimer's disease (AD) is characterized not only by cognitive and
      functional decline, but also often by the presence of neuropsychiatric symptoms.
      Apathy, which can be defined as a lack of motivation, is one of the most
      prevalent neuropsychiatric symptoms in AD and typically leads to a worse quality
      of life and greater burden for caregivers. Treatment options for apathy in AD are
      limited, but studies have examined the use of the amphetamine, methylphenidate.
      The Apathy in Dementia Methylphenidate Trial (ADMET) found that treatment of
      apathy in AD with methylphenidate was associated with significant improvement in
      apathy in two of three outcome measures, some evidence of improvement in global
      cognition, and minimal adverse events. However, the trial only enrolled 60
      participants who were followed for only 6 weeks. A larger, longer-lasting trial
      is required to confirm these promising findings. METHODS: The Apathy in Dementia
      Methylphenidate Trial 2 (ADMET 2) is a phase III, placebo-controlled, masked, 6
      month, multi-center, randomized clinical trial targeted to enroll 200
      participants with AD and apathy. Participants are randomly assigned 1:1 to 20 mg
      methylphenidate per day prepared as four over-encapsulated tablets or to matching
      placebo. The primary outcomes include (1) the mean difference in the
      Neuropsychiatric Inventory Apathy subscale scores measured as change from
      baseline to 6 months, and (2) the odds of having a given rating or better on the
      modified AD Cooperative Study Clinical Global Impression of Change ratings at
      month 6 compared with the baseline rating. Other outcomes include change in
      cognition, safety, and cost-effectiveness measured at monthly follow-up visits up
      to 6 months. DISCUSSION: Given the prevalence of apathy in AD and its impact on
      both patients and caregivers, an intervention to alleviate apathy would be of
      great benefit to society. ADMET 2 follows on the promising results from the
      original ADMET to evaluate the efficacy of methylphenidate as a treatment for
      apathy in AD. With a larger sample size and longer follow up, ADMET 2 is poised
      to confirm or refute the original ADMET findings. TRIAL REGISTRATION:
      ClinicalTrials.gov, NCT02346201 . Registered on 26 January 2015.

PMID- 29348000
TI  - Biodegradation and Metabolism of Tetrabromobisphenol A (TBBPA) in the
      Bioaugmented Activated Sludge Batch Bioreactor System by Heterotrophic and
      Nitrifying Bacteria.
AB  - Tetrabromobisphenol A [2,4'-isopropylidenebis(2,6-dibromophenol)] has been
      identified in wastewater samples collected from the Guelph municipal wastewater
      treatment plant (GWWTP). In order to assess the kinetics and metabolic mechanisms
      of the dissolved TBBPA, bench scale experiments were completed with batch
      bioreactors. The biodegradation test was conducted by taking aerobic sludge from
      the conventional activated sludge reactor (CAS) and membrane bioreactor (MBR),
      and bioaugmenting both reactors with soil based strains of Bacillus brevis and
      Bacillus pumilus. This novel biodegradation process showed that the CAS
      bioreactor had a biodegradation rate of 0.127 d-1, while the sludge from the MBR
      had a biodegradation rate of 0.171 d-1. This is the first reported aerobic
      biodegradation of TBBPA by heterotrophic and nitrifying bacteria in an activated
      sludge bioreactor system. A tentative biotransformation metabolic scheme for
      TBBPA biodegradation and metabolite formation has been proposed as well.

PMID- 29348001
TI  - Zr-Metal Organic Framework and Derivatives for Adsorptive and Photocatalytic
      Removal of Acid Dyes.
AB  - To investigate effects of modification of MOFs on removal of acid dyes via
      adsorption and photodegradation, zirconium-based MOF, UiO-66, and its derivatives
      were synthesized. UiO-66 derivatives were prepared by using amine (NH2)
      containing ligand and incorporating carbon nanotubes (CNTs) and reduced graphene
      oxide (RGO). During the synthesis UiO-66-NH2, UiO-66-CNT and UiO-66-RGO, were
      obtained, respectively. While UiO-66-NH2 showed the enhanced adsorption capacity
      for acid dyes owing to the electrostatic attraction, CNTs were found to be the
      most effective addition to enhance the adsorption of acid dyes. However, the
      addition of RGO in UiO-66 (to form UiO-66-RGO) exhibited the highest removal
      efficiency via photodegradation compared to UiO-66 and other derivatives probably
      attributed to its unique layered morphology. The presence of NH2, CNTs and RGO
      not only significantly improved the adsorption capacity for acid dyes but also
      enabled these UiO-66 derivatives to exhibit photocatalytic activity under visible
      light irradiation.

PMID- 29348002
TI  - Evaluation of a Gravity Flow Membrane Bioreactor for Treating Municipal
      Wastewater.
AB  - The biomass concentrator reactor (BCR), a gravity flow membrane bioreactor
      (MBR) design, was evaluated for use in treating a municipal wastewater stream.
      The BCR operates with less than 2.5 cm of pressure head and uses a 3 to 4 mm
      thick tortuous path membrane with pore size ranging from 18 to 28 MUm to achieve
      solids separation. A two-stage, aerobic/anoxic reactor was evaluated for the
      removal of chemical oxygen demand (COD), ammonia, total nitrogen, and solids
      separation. The reactor was fed 72 L/day, with a hydraulic retention time of 9.3
      hours, and had a solids retention time of 20 days. The influent COD was reduced
      by 93%, whereas, influent ammonia was reduced below 0.1 mg/L and total nitrogen
      was reduced by 53.7%. A lack of readily biodegradable COD limited denitrification
      and thus total nitrogen removal. The reactor solids were retained completely in
      the reactor by the membrane for the duration of testing.

PMID- 29348003
TI  - The WaterHub at Emory University: Campus Resiliency through Decentralized Reuse.
AB  - In the spring of 2015, Emory University in Atlanta, GA, commissioned an
      innovative campuswide water reclamation and reuse system known as the
      WaterHub(r). Treating up to 400,000 gallons each day, the system can recycle the
      equivalent of two-thirds of the University's wastewater production and reduce the
      campus water footprint by up to 40 percent.One of the first district-scale water
      reuse systems in North America, the WaterHub mines wastewater from the campus
      sewer system and repurposes it for beneficial reuse on campus. In its first year
      of operation, the facility has treated more than 80 million gallons of campus
      wastewater and is expected to save millions of dollars in utility costs for the
      University over the next 20 years. The system represents a new age in commercial
      scale water management in which onsite, urban water reclamation facilities may be
      a new norm.

PMID- 29348004
TI  - Predictors and Clinical Outcomes of Next-Day Discharge After Minimalist
      Transfemoral Transcatheter Aortic Valve Replacement.
AB  - OBJECTIVES: This study sought to investigate predictors and safety of next-day
      discharge (NDD) after transcatheter aortic valve replacement (TAVR). BACKGROUND:
      Information about predictors and safety of NDD after TAVR is limited. METHODS:
      The study reviewed 663 consecutive patients who underwent elective balloon
      expandable TAVR (from July 2014 to July 2016) at our institution. We first
      determined predictors of NDD in patients who underwent minimalist transfemoral
      TAVR. After excluding cases with complications, we compared 30-day and 1-year
      outcomes between NDD patients and those with longer hospital stay using Cox
      regression adjusting for the Predicted Risk of Mortality provided by the Society
      of Thoracic Surgeons. The primary endpoint was the composite of mortality and
      readmission at 1 year. RESULTS: A total of 150 patients had NDD after TAVR and
      210 patients had non-NDD. Mean age and the Society of Thoracic Surgeons Predicted
      Risk of Mortality were 80.7 +/- 8.8 years and 6.6 +/- 3.7%, respectively.
      Predictors of NDD were male sex (odds ratio [OR]: 2.02; 95% confidence interval
      [CI]: 1.28 to 3.18), absence of atrial fibrillation (OR: 1.62; 95% CI: 1.02 to
      2.57), serum creatinine (OR: 0.71; 95% CI: 0.55 to 0.92), and age (OR: 0.95; 95%
      CI: 0.93 to 0.98). As expected, 84% of patients with complications had non-NDD.
      After excluding cases with complications, there was no difference in hazard rates
      of the 30-day composite outcome between NDD and non-NDD (hazard ratio: 0.62; 95%
      CI: 0.20 to 1.91), but the hazard of the composite outcome at 1 year was
      significantly lower in the NDD group (hazard ratio: 0.47; 95% CI: 0.27 to 0.81).
      This difference in the composite outcome can be explained by the lower hazard of
      noncardiovascular related readmission in the NDD group. CONCLUSIONS: Factors
      predicting NDD include male sex, absence of atrial fibrillation, lower serum
      creatinine, and younger age. When compared with patients without complications
      with a longer hospital stay, NDD appears to be safe, achieving similar 30-day and
      superior 1-year clinical outcomes.

PMID- 29348005
TI  - Next-Day Discharge After Transcatheter Aortic Valve Replacement: A Goal or a
      Consequence?

PMID- 29348006
TI  - Importance of Contrast Aortography With Lotus Transcatheter Aortic Valve
      Replacement: A Post Hoc Analysis From the RESPOND Post-Market Study.
AB  - OBJECTIVES: The aim of this post hoc analysis from the RESPOND (Repositionable
      Lotus Valve System-Post-Market Evaluation of Real World Clinical Outcomes) post
      market study was to assess the final implantation depth on the contrast aortogram
      after Lotus valve (Boston Scientific, Marlborough, Massachusetts) transcatheter
      aortic valve replacement (TAVR) and to correlate with permanent pacemaker
      implantation (PPI) and paravalvular leak (PVL). BACKGROUND: Contrast aortography
      allows for the assessment of implantation depth and PVL during and after TAVR.
      Previous reports suggested an association between final device position and rates
      of PPI and PVL. METHODS: The RESPOND study was a prospective, open-label, single
      arm study in 41 centers evaluating outcomes after Lotus TAVR in routine clinical
      practice. Aortograms were collected at the Erasmus Medical Center and analyzed by
      researchers who were blinded to clinical outcomes. The primary analysis
      correlated implantation depth with PPI and PVL and required aortograms in a
      coaxial projection. The relation between implantation depth and need for PPI was
      assessed by multivariate logistic regression, adjusting for pre-defined
      confounders. A secondary analysis compared PVL analysis by contrast aortography
      with transthoracic echocardiography (TTE) performed by the independent core
      laboratory. RESULTS: A total of 724 angiographic studies were included in this
      analysis. Mean Lotus implantation depth was 6.67 +/- 2.19 mm. The overall PPI
      rate was 35%. PPI rate was lower with shallow implants (<6.5 mm: 21% vs. >=6.5
      mm: 41%; p < 0.001). After adjustment for confounders, implantation depth
      independently predicted need for PPI (odds ratio per 1-mm increment in depth:
      1.200; 95% confidence interval: 1.091 to 1.319; p = 0.002). More than trivial PVL
      was present in 23% by contrast aortography and in 8% by TTE. Implantation depth
      was not correlated with PVL by contrast aortography or TTE (p = 0.342 and p =
      0.149, respectively). PVL grading by contrast aortography and TTE was concordant
      in 77%. CONCLUSIONS: In this post hoc analysis of the RESPOND study PPI was
      highly correlated with implantation depth, whereas PVL was not. Higher Lotus
      implantation may reduce need for PPI.

PMID- 29348007
TI  - Assessing Implant Depth Using Aortography in Transcatheter Aortic Valve
      Replacement: What You See May Not Be What You Get.

PMID- 29348009
TI  - Valve in Valve for Failed Surgical Bioprostheses: Not for Everyone!

PMID- 29348008
TI  - Impact of Pre-Existing Prosthesis-Patient Mismatch on Survival Following Aortic
      Valve-in-Valve Procedures.
AB  - OBJECTIVES: The aim of this study was to determine whether the association of
      small label size of the surgical valve with increased mortality after
      transcatheter valve-in-valve (ViV) implantation is, at least in part, related to
      pre-existing prosthesis-patient mismatch (PPM) (i.e., a bioprosthesis that is too
      small in relation to body size). BACKGROUND: Transcatheter ViV implantation is an
      alternative for the treatment of patients with degenerated bioprostheses. Small
      label size of the surgical valve has been associated with increased mortality
      after ViV implantation. METHODS: Data from 1,168 patients included in the VIVID
      (Valve-in-Valve International Data) registry were analyzed. Pre-existing PPM of
      the surgical valve was determined using a reference value of effective orifice
      area for each given model and size of implanted prosthetic valve indexed for body
      surface area. Severe PPM was defined according to the criteria proposed by the
      Valve Academic Research Consortium 2: indexed effective orifice area <0.65 cm2/m2
      if body mass index is <30 kg/m2 and <0.6 cm2/m2 if BMI is >=30 kg/m2. The primary
      study endpoint was 1-year mortality. RESULTS: Among the 1,168 patients included
      in the registry, 89 (7.6%) had pre-existing severe PPM. Patients with severe PPM
      had higher 30-day (10.3%, p = 0.01) and 1-year (unadjusted: 28.6%, p < 0.001;
      adjusted: 19.3%, p = 0.03) mortality rates compared with patients with no severe
      PPM (4.3%, 11.9%, and 10.9%, respectively). After adjusting for surgical valve
      label size, Society of Thoracic Surgeons score, renal failure, diabetes, and
      stentless surgical valves, presence of pre-existing severe PPM was associated
      with increased risk for 1-year mortality (odds ratio: 1.88; 95% confidence
      interval: 1.07 to 3.28; p = 0.03). Patients with severe PPM also more frequently
      harbored high post-procedural gradients (mean gradient >=20 mm Hg). CONCLUSIONS:
      Pre-existing PPM of the failed surgical valve is strongly and independently
      associated with increased risk for mortality following ViV implantation.

PMID- 29348010
TI  - Early Outcomes With the Evolut PRO Repositionable Self-Expanding Transcatheter
      Aortic Valve With Pericardial Wrap.
AB  - OBJECTIVES: This study sought to evaluate the Medtronic Evolut PRO Transcatheter
      Aortic Valve System in patients with severe symptomatic aortic stenosis.
      BACKGROUND: A next-generation self-expanding transcatheter aortic valve was
      designed with an external pericardial wrap with the intent to reduce paravalvular
      leak while maintaining the benefits of a low-profile, self-expanding, and
      repositionable supra-annular valve. METHODS: The Medtronic Evolut PRO Clinical
      Study included 60 patients undergoing transcatheter aortic valve replacement with
      the Evolut PRO valve at 8 investigational sites in the United States. Clinical
      outcomes at 30 days were evaluated using Valve Academic Research Consortium-2
      criteria. The 2 primary safety endpoints were the incidence of all-cause
      mortality at 30 days and the incidence of disabling stroke at 30 days. The
      primary efficacy endpoint was the proportion of patients with no or trace
      prosthetic valve regurgitation at 30 days. An independent echocardiographic core
      laboratory (Mayo Clinic, Rochester, Minnesota) was used to adjudicate all
      echocardiographic assessments. RESULTS: All 60 patients received the Evolut PRO
      valve. At 30 days, 1 patient (1.7%) died and 1 patient (1.7%) experienced a
      nonfatal disabling stroke. Paravalvular regurgitation at 30 days was absent or
      trace in 72.4% of patients and was mild in the remainder of patients, with no
      patients having worse than mild paravavlular leak. The mean atrioventricular
      gradient was 6.4 +/- 2.1 mm Hg and effective orifice area was 2.0 +/- 0.5 cm2 at
      30 days. CONCLUSIONS: The safety and efficacy results of this study support the
      use of the Evolut PRO System for the treatment of severe symptomatic aortic
      stenosis in patients who are at increased surgical risk, resulting in excellent
      hemodynamics and minimal paravalvular leak (The Medtronic TAVR 2.0 US Clinical
      Study; NCT02738853).

PMID- 29348011
TI  - Sealing the Achilles Heel of Transcatheter Aortic Valve Replacement?

PMID- 29348012
TI  - Coronary Embolus: An Underappreciated Cause of Acute Coronary Syndromes.
AB  - Coronary embolism is the underlying cause of 3% of acute coronary syndromes but
      is often not considered in the differential of acute coronary syndromes. It
      should be suspected in the case of high thrombus burden despite a relatively
      normal underlying vessel or recurrent coronary thrombus. Coronary embolism may be
      direct (from the aortic valve or left atrial appendage), paroxysmal (from the
      venous circulation through a patent foramen ovale), or iatrogenic (following
      cardiac intervention). Investigations include transesophageal echocardiography to
      assess the left atrial appendage and atrial septum and continuous
      electrocardiographic monitoring to assess for paroxysmal atrial fibrillation. The
      authors review the historic and contemporary published data about this important
      cause of acute coronary syndromes. The authors propose an investigation and
      management strategy for work-up and anticoagulation strategy for patients with
      suspected coronary embolism.

PMID- 29348014
TI  - Bioresorbable Vascular Scaffolds in In-Stent Restenosis.

PMID- 29348013
TI  - Dose-Dependent Cardioprotection of Moderate (32 degrees C) Versus Mild (35
      degrees C) Therapeutic Hypothermia in Porcine Acute Myocardial Infarction.
AB  - OBJECTIVES: The study investigated whether a dose response exists between
      myocardial salvage and the depth of therapeutic hypothermia. BACKGROUND: Cardiac
      protection from mild hypothermia during acute myocardial infarction (AMI) has
      yielded equivocal clinical trial results. Rapid, deeper hypothermia may improve
      myocardial salvage. METHODS: Swine (n = 24) undergoing AMI were assigned to 3
      reperfusion groups: normothermia (38 degrees C) and mild (35 degrees C) and
      moderate (32 degrees C) hypothermia. One-hour anterior myocardial ischemia was
      followed by rapid endovascular cooling to target reperfusion temperature. Cooling
      began 30 min before reperfusion. Target temperature was reached before
      reperfusion and was maintained for 60 min. Infarct size (IS) was assessed on day
      6 using cardiac magnetic resonance, triphenyl tetrazolium chloride, and
      histopathology. RESULTS: Triphenyl tetrazolium chloride area at risk (AAR) was
      equivalent in all groups (p = 0.2), but 32 degrees C exhibited 77% and 91%
      reductions in IS size per AAR compared with 35 degrees C and 38 degrees C,
      respectively (AAR: 38 degrees C, 45 +/- 12%; 35 degrees C, 17 +/- 10%; 32 degrees
      C, 4 +/- 4%; p < 0.001) and comparable reductions per LV mass (LV mass: 38
      degrees C, 14 +/- 5%; 35 degrees C, 5 +/- 3%; 32 degrees C 1 +/- 1%; p < 0.001).
      Importantly, 32 degrees C showed a lower IS AAR (p = 0.013) and increased
      immunohistochemical granulation tissue versus 35 degrees C, indicating higher
      tissue salvage. Delayed-enhancement cardiac magnetic resonance IS LV also showed
      marked reduction at 32 degrees C (38 degrees C: 10 +/- 4%, p < 0.001; 35 degrees
      C: 8 +/- 3%; 32 degrees C: 3 +/- 2%, p < 0.001). Cardiac output on day 6 was only
      preserved at 32 degrees C (reduction in cardiac output: 38 degrees C, -29 +/-
      19%, p = 0.041; 35 degrees C: -17 +/- 33%; 32 degrees C: -1 +/- 28%, p = 0.041).
      Using linear regression, the predicted IS reduction was 6.7% (AAR) and 2.1% (LV)
      per every 1 degrees C reperfusion temperature decrease. CONCLUSIONS: Moderate (32
      degrees C) therapeutic hypothermia demonstrated superior and near-complete
      cardioprotection compared with 35 degrees C and control, warranting further
      investigation into clinical applications.

PMID- 29348015
TI  - Reply: Bioresorbable Vascular Scaffolds in In-Stent Restenosis.

PMID- 29348016
TI  - Effect of Modern Dose-Reduction Technology on the Exposure of Interventional
      Cardiologists to Radiation in the Catheterization Laboratory.

PMID- 29348017
TI  - A Pilot Study for Left Atrial Appendage Occlusion Guided by 3-Dimensional
      Rotational Angiography Alone.

PMID- 29348018
TI  - Myocardial Inflammation Predicts Remodeling and Neuroinflammation After
      Myocardial Infarction.
AB  - BACKGROUND: The local inflammatory tissue response after acute myocardial
      infarction (MI) determines subsequent healing. Systemic interaction may induce
      neuroinflammation as a precursor to neurodegeneration. OBJECTIVES: This study
      sought to assess the influence of MI on cardiac and brain inflammation using
      noninvasive positron emission tomography (PET) of the heart-brain axis. METHODS:
      After coronary artery ligation or sham surgery, mice (n = 49) underwent serial
      whole-body PET imaging of the mitochondrial translocator protein (TSPO) as a
      marker of activated macrophages and microglia. Patients after acute MI (n = 3)
      were also compared to healthy controls (n = 9). RESULTS: Infarct mice exhibited
      elevated myocardial TSPO signal at 1 week versus sham (percent injected dose per
      gram: 8.0 +/- 1.6 vs. 4.8 +/- 0.9; p < 0.001), localized to activated CD68+
      inflammatory cells in the infarct. Early TSPO signal predicted subsequent left
      ventricular remodeling at 8 weeks (rpartial = -0.687; p = 0.001). In parallel,
      brain TSPO signal was elevated at 1 week (1.7 +/- 0.2 vs. 1.4 +/- 0.2 for sham; p
      = 0.017), localized to activated microglia. After interval decline at 4 weeks,
      progressive heart failure precipitated a second wave of neuroinflammation (1.8 +/
      0.2; p = 0.005). TSPO was concurrently up-regulated in remote cardiomyocytes at
      8 weeks (8.8 +/- 1.7, p < 0.001) without inflammatory cell infiltration,
      suggesting mitochondrial impairment. Angiotensin-converting enzyme inhibitor
      treatment lowered acute inflammation in the heart (p = 0.003) and brain (p =
      0.06) and improved late cardiac function (p = 0.05). Patients also demonstrated
      elevation of cardiac TSPO signal in the infarct territory, paralleled by
      neuroinflammation versus controls. CONCLUSIONS: The brain is susceptible to acute
      MI and chronic heart failure. Immune activation may interconnect heart and brain
      dysfunction, a finding that provides a foundation for strategies to improve heart
      and brain outcomes.

PMID- 29348019
TI  - Imaging Dynamic Heart-Brain Interactions: Getting to the Heart of the Matter,
      Gray and White.

PMID- 29348021
TI  - Learning From Patients With Ultrarare Conditions: Cholesterol Hoof Beats.

PMID- 29348020
TI  - Autosomal Recessive Hypercholesterolemia: Long-Term Cardiovascular Outcomes.
AB  - BACKGROUND: Autosomal recessive hypercholesterolemia (ARH) is a rare lipid
      disorder characterized by premature atherosclerotic cardiovascular disease
      (ASCVD). There are sparse data for clinical management and cardiovascular
      outcomes in ARH. OBJECTIVES: Evaluation of changes in lipid management,
      achievement of low-density lipoprotein cholesterol (LDL-C) goals and
      cardiovascular outcomes in ARH. METHODS: Published ARH cases were identified by
      electronic search. All corresponding authors and physicians known to treat these
      patients were asked to provide follow-up information, using a standardized
      protocol. RESULTS: We collected data for 52 patients (28 females, 24 males; 31.1
      +/- 17.1 years of age; baseline LDL-C: 571.9 +/- 171.7 mg/dl). During a mean
      follow-up of 14.1 +/- 7.3 years, there was a significant increase in the use of
      high-intensity statin and ezetimibe in combination with lipoprotein apheresis; in
      6 patients, lomitapide was also added. Mean LDL-C achieved at nadir was 164.0 +/-
      85.1 mg/dl (-69.6% from baseline), with a better response in patients taking
      lomitapide (-88.3%). Overall, 23.1% of ARH patients reached LDL-C of <100 mg/dl.
      During follow-up, 26.9% of patients had incident ASCVD, and 11.5% had a new
      diagnosis of aortic valve stenosis (absolute risk per year of 1.9% and 0.8%,
      respectively). No incident stroke was observed. Age (>=30 years) and the presence
      of coronary artery disease at diagnosis were the major predictors of incident
      ASCVD. CONCLUSIONS: Despite intensive treatment, LDL-C in ARH patients remains
      far from targets, and this translates into a poor long-term cardiovascular
      prognosis. Our data highlight the importance of an early diagnosis and treatment
      and confirm the fact that an effective treatment protocol for ARH is still
      lacking.

PMID- 29348022
TI  - Identifying and Treating Young Patients at Risk for Cardiovascular Events.

PMID- 29348023
TI  - Impaired Recovery of Left Ventricular Function in Patients With Cardiomyopathy
      and Left Bundle Branch Block.
AB  - BACKGROUND: Patients with left bundle branch block (LBBB) often respond to
      cardiac resynchronization therapy (CRT) with left ventricular ejection fraction
      (LVEF) improvement. Guideline-directed medical therapy (GDMT), not CRT, is first
      line therapy for patients with reduced LVEF with LBBB. However, there are little
      data on how patients with reduced LVEF and LBBB respond to GDMT. OBJECTIVES: This
      study examined patients with cardiomyopathy and sought to assess rates of LVEF
      improvement for patients with LBBB compared to other QRS morphologies. METHODS:
      Using data from the Duke Echocardiography Laboratory Database, the study
      identified patients with baseline electrocardiography and LVEF <=35% who had a
      follow-up LVEF 3 to 6 months later. The study excluded patients with severe valve
      disease, a cardiac device, left ventricular assist device, or heart transplant.
      QRS morphology was classified as LBBB, QRS duration <120 ms (narrow QRS
      duration), or a wide QRS duration >=120 ms but not LBBB. Analysis of variance
      testing compared mean change in LVEF among the 3 groups with adjustment for
      significant comorbidities and GDMT. RESULTS: There were 659 patients that met the
      criteria: 111 LBBB (17%), 59 wide QRS duration >=120 ms but not LBBB (9%), and
      489 narrow QRS duration (74%). Adjusted mean increase in LVEF over 3 to 6 months
      in the 3 groups was 2.03%, 5.28%, and 8.00%, respectively (p < 0.0001). Results
      were similar when adjusted for interim revascularization and myocardial
      infarction. Comparison of mean LVEF improvement between patients with LBBB on
      GDMT and those not on GDMT showed virtually no difference (3.50% vs. 3.44%). The
      combined endpoint of heart failure hospitalization or mortality was highest for
      patients with LBBB. CONCLUSIONS: LBBB is associated with a smaller degree of LVEF
      improvement compared with other QRS morphologies, even with GDMT. Some patients
      with LBBB may benefit from CRT earlier than guidelines currently recommend.

PMID- 29348024
TI  - Cardiomyopathy and Left Bundle Branch Block: A Farewell to Drugs?

PMID- 29348026
TI  - Imaging the Intersection of Oxidative Stress, Lipids, and Inflammation: Progress
      Toward Personalized Care of Atherosclerosis.

PMID- 29348025
TI  - PET/MR Imaging of Malondialdehyde-Acetaldehyde Epitopes With a Human Antibody
      Detects Clinically Relevant Atherothrombosis.
AB  - BACKGROUND: Oxidation-specific epitopes (OSEs) are proinflammatory, and elevated
      levels in plasma predict cardiovascular events. OBJECTIVES: The purpose of this
      study was to develop novel positron emission tomography (PET) probes to
      noninvasively image OSE-rich lesions. METHODS: An antigen-binding fragment (Fab)
      antibody library was constructed from human fetal cord blood. After multiple
      rounds of screening against malondialdehyde-acetaldehyde (MAA) epitopes, the Fab
      LA25 containing minimal nontemplated insertions in the CDR3 region was identified
      and characterized. In mice, pharmacokinetics, biodistribution, and plaque
      specificity studies were performed with Zirconium-89 (89Zr)-labeled LA25. In
      rabbits, 89Zr-LA25 was used in combination with an integrated clinical
      PET/magnetic resonance (MR) system. 18F-fluorodeoxyglucose PET and dynamic
      contrast-enhanced MR imaging were used to evaluate vessel wall inflammation and
      plaque neovascularization, respectively. Extensive ex vivo validation was carried
      out through a combination of gamma counting, near infrared fluorescence,
      autoradiography, immunohistochemistry, and immunofluorescence. RESULTS: LA25
      bound specifically to MAA epitopes in advanced and ruptured human atherosclerotic
      plaques with accompanying thrombi and in debris from distal protection devices.
      PET/MR imaging 24 h after injection of 89Zr-LA25 showed increased uptake in the
      abdominal aorta of atherosclerotic rabbits compared with nonatherosclerotic
      control rabbits, confirmed by ex vivo gamma counting and autoradiography. 18F
      fluorodeoxyglucose PET, dynamic contrast-enhanced MR imaging, and near-infrared
      fluorescence signals were also significantly higher in atherosclerotic rabbit
      aortas compared with control aortas. Enhanced liver uptake was also noted in
      atherosclerotic animals, confirmed by the presence of MAA epitopes by
      immunostaining. CONCLUSIONS: 89Zr-LA25 is a novel PET radiotracer that may allow
      noninvasive phenotyping of high-risk OSE-rich lesions.

PMID- 29348027
TI  - Implications of Underlying Mechanisms for the Recognition and Management of
      Diabetic Cardiomyopathy.
AB  - Heart failure is a complex clinical syndrome, the incidence and prevalence of
      which is increased in diabetes mellitus, pre-diabetes, and obesity. Although this
      may arise from underlying coronary artery disease, it often occurs in the absence
      of significant major epicardial coronary disease, and most commonly manifests as
      heart failure with preserved ejection fraction. Despite epidemiological evidence
      linking diabetes to heart failure incidence and outcome, the presence of a
      distinct primary "diabetic" cardiomyopathy has been difficult to prove, because
      the link between diabetes and heart failure is confounded by hypertension,
      microvascular dysfunction, and autonomic neuropathy. Nonetheless, several
      mechanistic associations at systemic, cardiac, and cellular/molecular levels
      explain different aspects of myocardial dysfunction, including impaired cardiac
      relaxation, compliance, and contractility. This review seeks to describe recent
      advances and limitations pertinent to integrating molecular mechanisms, clinical
      screening, and potential therapeutic avenues for this condition.

PMID- 29348028
TI  - Antithrombotic Therapy in Peripheral Artery Disease: Generating and Translating
      Evidence Into Practice.
AB  - Atherosclerotic cardiovascular (CV) disease remains a major health concern
      affecting more than 200 million adults worldwide, and lower extremity peripheral
      artery disease (PAD) is associated with significant morbidity and mortality.
      Treatment strategies to reduce the burden of major adverse CV events and limb
      events have mainly involved the use of antiplatelet and statin medications.
      Unlike other types of atherosclerotic CV disease, the evidence base is not well
      developed for therapies in patients with PAD. Recently, studies from subgroups of
      patients with PAD and a large clinical trial of PAD patients have been published,
      signaling a burgeoning interest in studying this higher risk population. This
      review outlines the inherent CV risks of patients with PAD, risk reduction
      strategies, emerging clinical trial data, and opportunities for the CV community
      to generate evidence in real-world settings and translate evidence into practice
      as new therapies become available.

PMID- 29348029
TI  - Inorganic Nitrite Selectively Dilates Epicardial Coronary Arteries.

PMID- 29348030
TI  - Cardiovascular Mortality Reduction With Empagliflozin in Patients With Type 2
      Diabetes and Cardiovascular Disease.

PMID- 29348031
TI  - Left Ventricular Systolic Dysfunction in Transplantation Donor Hearts: Another
      Takotsubo Phenotype?

PMID- 29348032
TI  - Reply: Transient Wall Motion Abnormalities in Donor Hearts With Improved Left
      Ventricular Systolic Dysfunction: Takotsubo Revisited?

PMID- 29348033
TI  - Myocardial Dysfunction Following Brain Death.

PMID- 29348034
TI  - The new Brazilian legislation on access to the biodiversity (Law 13,123/15 and
      Decree 8772/16).

PMID- 29348035
TI  - Alzheimer's disease, cellular prion protein, and dolphins.

PMID- 29348036
TI  - Increasing Traction for Discovery: The Research Domain Criteria Framework and
      Neurodevelopmental Disorders.

PMID- 29348037
TI  - Obligatory Processing of Task-Irrelevant Stimuli: A Hallmark of Autistic
      Cognitive Style Within and Beyond the Diagnosis.

PMID- 29348038
TI  - Children With Fragile X Syndrome Display Threat-Specific Biases Toward Emotion.
AB  - BACKGROUND: Fragile X syndrome (FXS) is the most common form of inherited
      intellectual disability. FXS is caused by a silencing of the FMR1 gene that
      results in a loss or absence of the gene's protein product, fragile X mental
      retardation protein. The phenotype of FXS is consistently associated with
      heightened anxiety, although no previous study has investigated attentional bias
      toward threat, a hallmark of anxiety disorders, in individuals with FXS. METHODS:
      The current study employed a passive-viewing eye-tracking version of the dot
      probe task to investigate attentional biases toward emotional faces in young
      children with FXS (n = 47) and without FXS (n = 94). RESULTS: We found that the
      FXS group showed a significantly greater bias toward threatening emotions than
      toward positive emotions. This threat specificity was not seen in either a mental
      age-matched group or a chronological age-matched group of typically developing
      children. Unlike the typically developing groups, the FXS group showed no bias
      toward positive emotion. CONCLUSIONS: The current study shows that children with
      FXS have a significant bias toward threatening information, an attentional
      profile that has been linked with anxiety. It also supports the use of eye
      tracking methodology to index neural and attentional responses in young children
      with FXS.

PMID- 29348039
TI  - Face Processing Measures of Social Cognition: A Dimensional Approach to
      Developmental Psychopathology.
AB  - BACKGROUND: Social cognition impairments in neurodevelopmental disorders impact
      functioning. Face processing is the most extensively studied aspect of social
      cognition, commonly indexing this construct in neuropsychiatric disorders
      compared with typically developing youths. Applying social cognition measures as
      a Research Domain Criteria concept in the clinical arena requires establishing
      cutoffs for intervention and identifying vulnerability for psychopathology across
      disorders. This can be accomplished by comparing extreme performers across
      multiple clinical symptom features. METHODS: The Philadelphia Neurodevelopmental
      Cohort (N = 9498), a community sample of youths (8-21 years old), was assessed
      with a structured interview (Kiddie Schedule for Affective Disorders and
      Schizophrenia). The Penn Computerized Neurocognitive Battery was administered
      measuring accuracy and response time on Executive, Episodic Memory, Complex
      Cognition, and Social Cognition domains. We parsed participants by performance on
      social cognition into tertiles and examined their neurocognitive and clinical
      profiles. RESULTS: The top social cognition group outperformed the bottom group
      in face memory and complex reasoning. Concerning symptoms, the top performing
      group did not differ from the middle group, but the bottom performing group had
      higher externalizing and psychosis symptoms. There were sex differences in social
      cognition and symptom profiles but no sex * performance or sex * diagnosis *
      domain interactions. CONCLUSIONS: Social cognition is supported by strong face
      memory and complex reasoning skills. Poor performance portends more severe
      externalizing and psychosis symptoms. That average performance is sufficient for
      normative symptomatology suggests that interventions aimed at ameliorating social
      cognition deficits, as measured here, could be effective in normalizing level of
      symptoms.

PMID- 29348040
TI  - Negative Valence in Autism Spectrum Disorder: The Relationship Between Amygdala
      Activity, Selective Attention, and Co-occurring Anxiety.
AB  - BACKGROUND: A critical agenda of the National Institutes of Health Research
      Domain Criteria (RDoC) initiative is establishing whether domains within the RDoC
      matrix are truly transdiagnostic. Rates of anxiety disorders are elevated in
      autism spectrum disorder (ASD), but it is unclear whether the same mechanisms
      contribute to anxiety in individuals with and without ASD. As changes in
      selective attention are a hallmark of anxiety disorders in non-ASD samples, the
      identification of these changes in ASD would support the transdiagnostic nature
      of anxiety. METHODS: This functional magnetic resonance imaging study focused on
      the negative valence domain from RDoC (manifest as anxiety symptoms) in youth
      with ASD (n = 38) and typically developing control participants (n = 25). The
      task required selective attention toward and away from social information (faces)
      with negative and neutral affect. Participants underwent in-depth
      characterization for both anxiety and ASD symptoms. RESULTS: Dimensional and
      categorical measures of anxiety were significantly related to increased amygdala
      activation-evidence of enhanced attentional capture by social information.
      CONCLUSIONS: This pattern fits with decades of research among non-ASD samples
      using selective attention and attentional bias paradigms, suggesting that anxiety
      in ASD shares mechanisms with anxiety alone. Overall, results from this study
      support the transdiagnostic nature of the negative valence domain from RDoC and
      increase the likelihood that anxiety in ASD should be responsive to interventions
      targeting maladaptive responses to negative information.

PMID- 29348042
TI  - Zinc-aluminum oxide solid solution nanosheets obtained by pyrolysis of layered
      double hydroxide as the photoanodes for dye-sensitized solar cells.
AB  - Due to the superiority of metal-doped ZnO compared to TiO2, the Zn-M (M = Al3+,
      Ga3+, Cr3+, Ti4+, Ce4+) mixed metal oxide solid solutions have been extensively
      studied for photocatalytic and photovoltaic applications. In this work, a
      systematic research has proceeded for the preparation of a zinc-aluminum oxide
      semiconductor as a photoanode for the dye-sensitized solar cells (DSSCs) by a
      simple pyrolysis route with the Zn-Al layered double hydroxide (LDH) as a
      precursor. The Zn-Al oxide solid solution has been applied for DSSCs as an
      electron acceptor, which is used to study the influence of different Al content
      and sintering temperature on the device efficiency. Finally, the Zn-Al oxide
      solid solution with calcination temperature 600  degrees C and Al 27 at.% content
      exhibits the best performance. The photoelectric efficiency improved 100 times
      when the Al3+ content decreased from 44 to 27 at.%. The ZnxAlyO solid solution
      show a reasonable efficiency as photoanode materials in DSSCs, with the best
      preliminary performance reported so far, and shows its potential application for
      the photovoltaic devices.

PMID- 29348041
TI  - Executive Dysfunction in Autism Spectrum Disorder Is Associated With a Failure to
      Modulate Frontoparietal-insular Hub Architecture.
AB  - BACKGROUND: Comorbid executive dysfunction in autism spectrum disorder (ASD) is a
      barrier to adaptive functioning, despite remittance of core social-communication
      symptoms. Network models of ASD address core symptoms but not comorbid executive
      dysfunction. Following recent demonstrations in healthy adults that, with
      increasing executive demands, hubs embedded within frontoparietal-insular control
      networks interact with a more diverse set of networks, we hypothesized that the
      capability of hubs to do so is perturbed in ASD and predicts executive behavior.
      METHODS: Seventy-five 7- to 13-year-old children with ASD (n = 35) and age- and
      IQ-matched typically developing control subjects (n = 40) completed both a
      resting-state and a selective attention task functional magnetic resonance
      imaging session. We assessed changes in the participation coefficient, a graph
      theory metric indexing hubness, of 264 brain regions comprising 12 functional
      networks between the two sessions. Parent reported executive impairment in
      everyday life was measured using the Behavior Rating Inventory of Executive
      Function. RESULTS: The participation coefficient of the frontoparietal-insular
      cortex, including core nodes of the frontoparietal control and salience networks,
      significantly increased in typically developing children but not in children with
      ASD during the task relative to rest. Change in frontoparietal-insular
      participation coefficient predicted Behavior Rating Inventory of Executive
      Function scores indexing the ability to attend to task-oriented output, plan and
      organize, and sustain working memory. CONCLUSIONS: Our results suggest that
      executive impairments in ASD emerge from a failure of frontoparietal-insular
      control regions to function as adaptive and integrative hubs in the brain's
      functional network architecture. Our results also demonstrate the utility of
      examining dynamic network function for elucidating potential biomarkers for
      disorders with comorbid executive dysfunction.

PMID- 29348043
TI  - Superhydrophobic coatings with high repellency to daily consumed liquid foods
      based on food grade waxes.
AB  - The applications of superhydrophobic coatings in daily life are receiving
      increasing attention. Here, we report a general approach for preparing
      superhydrophobic coatings with high repellency to daily consumed liquid foods
      based on food grade waxes. The coatings are prepared by spray-coating the
      homogeneous wax suspensions in ethanol followed by annealing at 40  degrees C.
      The wax suspensions are formed by the heating dissolution-cooling precipitation
      ultrasonication process thanks to the unique solubility of the waxes in ethanol.
      Ultrasonication of the wax suspension is helpful to improve superhydrophobicity
      by reducing the size of the wax microplatelets. Annealing at 40  degrees C could
      enhance mechanical stability of the coatings. The coatings are superhydrophobic
      with a water contact angle of 158.2 degrees  and a sliding angle of 7.3 degrees .
      The coatings are resistant to intense water jetting and immersion in corrosive
      aqueous solutions. In addition, the coatings show excellent anti-adhesive
      properties for various liquid foods including cola, honey, milk and yoghourt.
      Moreover, the coatings are applicable onto different substrates (e.g., glass
      slide, PET plate and polyethylene plate) and could be prepared using different
      waxes (e.g., paraffin wax, beeswax and microcrystalline wax). We believe that the
      wax superhydrophobic coatings could find applications in various fields such as
      anti-adhesion of liquid foods, fruit preservation and anti-bioadhesion, etc.

PMID- 29348044
TI  - Wetting of flat gradient surfaces.
AB  - Gradient, chemically modified, flat surfaces enable directed transport of
      droplets. Calculation of apparent contact angles inherent for gradient surfaces
      is challenging even for atomically flat ones. Wetting of gradient, flat solid
      surfaces is treated within the variational approach, under which the contact line
      is free to move along the substrate. Transversality conditions of the variational
      problem give rise to the generalized Young equation valid for gradient solid
      surfaces. The apparent (equilibrium) contact angle of a droplet, placed on a
      gradient surface depends on the radius of the contact line and the values of
      derivatives of interfacial tensions. The linear approximation of the problem is
      considered. It is demonstrated that the contact angle hysteresis is inevitable on
      gradient surfaces. Electrowetting of gradient surfaces is discussed.

PMID- 29348045
TI  - Supplementary motor area-primary motor cortex facilitation in younger but not
      older adults.
AB  - Growing evidence implicates a decline in white matter integrity in the age
      related decline in motor control. Functional neuroimaging studies show
      significant associations between functional connectivity in the cortical motor
      network, including the supplementary motor area (SMA), and motor performance.
      Dual-coil transcranial magnetic stimulation studies show facilitatory connections
      between SMA and the primary motor cortex (M1) in younger adults. Here, we
      investigated whether SMA-M1 facilitation is affected by age and whether the
      strength of SMA-M1 facilitation is associated with bilateral motor control. Dual
      coil transcranial magnetic stimulation was used to measure SMA-M1 connectivity in
      younger (N = 20) and older adults (N = 18), and bilateral motor control was
      measured with the assembly subtest of the Purdue Pegboard and clinical measures
      of dynamic balance. SMA-M1 facilitation was seen in younger but not older adults,
      and a significant positive association was found between SMA-M1 facilitation and
      bimanual performance. These results show that SMA-M1 facilitation is reduced in
      older adults compared to younger adults and provide evidence of the functional
      importance of SMA-M1 facilitation.

PMID- 29348046
TI  - Synthesis of sulfamide analogues of deoxthymidine monophosphate as potential
      inhibitors of mycobacterial cell wall biosynthesis.
AB  - The recently discovered enzyme Mycobacterium tuberculosis thymidine monophosphate
      kinase (TMPKmt), which catalyses the phosphorylation of deoxythymidine
      monophosphate (dTMP) to give deoxythymidine diphosphate (dTDP), is indispensable
      for the growth and survival of M. tuberculosis as it plays an essential role in
      DNA synthesis. Inhibition of TMPKmt is an attractive avenue for the development
      of novel anti-tuberculosis agents. Based on the premise that sulfamide may be a
      suitable isostere of phosphate, deoxythymidine analogues comprising various
      substituted sulfamides at C5' were modelled in silico into the active site of
      TMPKmt (PDB accession code: 1N5K) using induced-fit docking methods. A selection
      of modelled compounds was synthesized, and their activity as inhibitors of TMPKmt
      was evaluated. Three compounds showed competitive inhibition of TMPKmt in the
      micromolar range (10-50 MUM). Compounds were tested in vitro for anti
      mycobacterial activity against M. smegmatis: three compounds showed weak anti
      mycobacterial activity (MIC 250 MUg/mL).

PMID- 29348047
TI  - Effects of inorganic ions and natural organic matter on the aggregation of
      nanoplastics.
AB  - The aggregation of nanoplastics (NPs) is a key issue in understanding the dynamic
      nature of NPs in the environment. The aggregation of NPs under various
      environmental conditions has not yet been studied. We investigated the influences
      of inorganic ions and natural organic matter (NOM) on polystyrene (PS) NPs
      aggregation in solutions. Results showed that PS NPs remained stable in wide
      ionic strength solutions of NaCl (1-100 mM) and CaCl2 (0.1-15 mM), and only in
      low ionic strength FeCl3 solutions (0.01 mM). However, obvious PS NPs aggregation
      was observed in FeCl3 solutions with an increase in ionic strength (0.1 and 1
      mM). Moreover, NOM had a negligible effect on PS NPs aggregation in all ionic
      strengths of NaCl and CaCl2 solutions and in low ionic strength FeCl3 solutions
      (0.01 mM). However, NOM reduced PS NPs aggregation in an intermediate ionic
      strength FeCl3 (0.1 mM) solution and increased aggregation in a high ionic
      strength FeCl3 (1 mM) solution. Based on the theoretical analysis of interaction
      forces among PS NPs, the Derjaguin-Landau-Verwey-Overbeek force was a contributor
      governing PS NPs aggregation either in the absence or presence of NOM. In
      addition, other factors, including electrostatic heterogeneity of PS NPs
      surfaces, steric repulsion induced by NOM, and clusters formed via bridging
      effect in the presence of NOM also contributed to altered PS NPs aggregation
      under selected conditions. The PS NPs-NOM clusters were directly observed using a
      cryogenic scanning electron microscope.

PMID- 29348048
TI  - Identification of number and type of cations in water-soluble Cs+ and Na+
      calix[4]arene-bis-crown-6 complexes by using ESI-TOF-MS.
AB  - The treatment of cesium-contaminated wastewater has become one of the biggest
      issues. The selective Cs+ removal from wastewater containing competitive alkali
      metal ions such as Na+ is desired to reduce the volume of sludge. Therefore, the
      present work focused on water-soluble calix[4]arene-bis-crown-6 (W-BisC6) to
      selectively capture Cs+. For characterization of the complex, UV-vis spectroscopy
      is commonly used, however, due to the limited availability of information it can
      be hard to quickly identify the specific structures of some complexes. In this
      work, the electrospray ionization time of flight spectrometry (ESI-TOF-MS) is
      successfully utilized to identify the number and type of cations in W-BisC6
      cation complexes. ESI-TOF-MS accurately recognized 4 types of complex (W-BisC6
      Na+, W-BisC6-Cs+, W-BisC6-2Na+, W-BisC6-Na+-Cs+), and the experimental and
      simulated results were almost perfectly matched. It also revealed the difficulty
      of W-BisC6-2Cs+ complex formation under the present conditions. Thus, this
      technique is significantly helpful for rapid identification of the specific
      structures of complexes during Cs+-contaminated wastewater treatment.

PMID- 29348050
TI  - Do estimates of blood loss differ between student midwives and midwives? A
      multicenter cross-sectional study.
AB  - OBJECTIVE: the principal objective of this study was to assess the quality of
      blood loss estimates by midwives and student midwives. The secondary objectives
      were: to assess the intraobserver agreement of visual blood estimates and the
      rate of underestimation of blood loss by participants, and to estimate the
      sensitivity, specificity, and negative likelihood ratio of these estimates for
      clinically pertinent blood losses (>= 500mL and >= 1000mL). DESIGN: multicenter
      cross-sectional study. SETTING: thirty-three French maternity units and 35 French
      midwifery schools participated in this study. PARTICIPANTS: volunteer French
      midwifery students (n = 463) and practicing midwives (n = 578). INTERVENTION: an
      online survey showed 16 randomly ordered photographs of 8 different simulated
      blood quantities (100, 150, 200, 300, 500, 850, 1000, and 1500mL) with a
      reference 50-mL image in each photo and asked participants to estimate the blood
      loss. The visual blood loss estimates were compared with Fisher's exact test.
      Intraobserver agreement for these estimates was assessed with a weighted kappa
      coefficient, and the negative predictive values (probability of no hemorrhage
      when visual estimate was negative) were calculated from prevalence rates in the
      literature. FINDINGS: of the 16,656 estimates obtained, 34.1% were accurate,
      37.2% underestimated the quantity presented, and 28.7% overestimated it. Analyses
      of the intraobserver reproducibility between the two estimates of the same
      photograph showed that agreement was highest (weighted kappa >= 0.8) for the
      highest values (1000mL, 1500mL). For each volume considered, students
      underestimated blood loss more frequently than midwives. In both groups, the
      negative predictive values regarding postpartum hemorrhage (PPH) diagnosis
      (severe or not) were greater than 98%. KEY CONCLUSIONS AND IMPLICATIONS FOR
      PRACTICE: student midwives tended to underestimate the quantity of blood loss
      more frequently than the midwives. Postpartum hemorrhage (>= 500mL) was always
      identified, but severe postpartum hemorrhage (>= 1000mL) was identified in fewer
      than half the cases. These results should be taken into account in training both
      student midwives and practicing professionals.

PMID- 29348049
TI  - CuI and CuII complexes with phosphine derivatives of fluoroquinolone antibiotics 
      A comparative study on the cytotoxic mode of action.
AB  - In this paper, we present a comparative study on the cytotoxic mode of action of
      copper(I) and copper(II) complexes with phosphine derivatives of fluoroquinolone
      antibiotics (ciprofloxacin HCp and norfloxacin HNr). The in vitro cytotoxic
      activity of four new compounds was tested against two selected cancer cell lines.
      All complexes exhibited much better cytotoxicity against both cell lines than
      unmodified fluoroquinolone antibiotics, their phosphines (PCp, PNr), chalcogenide
      derivatives (oxides: OPCp, OPNr; sulfides: SPCp, SPNr and selenides: SePCp,
      SePNr) and previously described by us complexes with phosphines derived from
      different fluoroquinolones: lomefloxacin (HLm) and sparfloxacin (HSf) as well as
      cisplatin. Apoptosis, observed at a great predominance, was induced by all
      studied complexes. Importantly, it was concluded that coordination compounds with
      Cu(I) ion ([CuI-PNr] and [CuI-PCp]) were much more active than those with Cu(II)
      ion ([OPNr-CuII], [OPCp-CuII]), even though the highest efficacy to produce
      reactive oxygen species, participating in overall cytotoxicity, was proved for
      copper(II) complexes among all studied compounds. Herein, we discuss not only
      results obtained for copper(I)/(II) complexes with phosphines derived from HNr
      and HCp but we also compare them to previously described data for complexes with
      HLm and HSf derivatives. This is the first insight into a structure-activity
      relationship of copper complexes with phosphine derivatives of fluoroquinolone
      antibiotics.

PMID- 29348051
TI  - Midwives understanding of physical activity guidelines during pregnancy.
AB  - OBJECTIVE: to examine the current level of understanding held by midwives
      regarding the NICE physical activity guidelines in the UK, and to investigate the
      physical activity guidance given to women during pregnancy. DESIGN: an 11
      question online survey comprising of a mixture of closed and open ended
      questions. SETTING: data reflects participants sampled across the United Kingdom.
      PARTICIPANTS: fifty-nine midwives completed the online survey MEASUREMENTS AND
      FINDINGS: an electronic survey was used to explore the midwives understanding of
      physical activity guidelines during pregnancy, and the advice they offered to
      women in their care. Qualitative content analysis was used to gain a more in
      depth understanding of midwife knowledge. Two per cent of midwives correctly
      identified the physical activity guidelines, with 44% giving partially correct
      responses, 25% giving incorrect responses and 29% unsure of what the guidelines
      are. Despite the low level of correct responses, 59% of respondents reported they
      were confident or very confident in answering questions regarding physical
      activity. Only 4% of respondents reported having access to continual professional
      development (CPD) in the area of PA guidance. KEY CONCLUSIONS: there appears to
      be a misplaced confidence amongst midwives in their knowledge of the NICE PA
      guidelines for pregnancy. IMPLICATIONS FOR PRACTICE: as physical inactivity can
      be detrimental for the health of both mother and baby, there is a clear need for
      better dissemination of the current and future NICE physical activity guidelines
      in primary health care settings. The current study determined a substantial lack
      of CPD in the area of PA guidance, which may be a contributing factor to the lack
      of knowledge of the guidelines. As such, increasing CPD may in turn improve the
      accuracy of the advice given to pregnant women and consequently benefit the
      health of both mother and baby.

PMID- 29348053
TI  - Multimodality imaging of endocrine immune related adverse events: a primer for
      radiologists.
AB  - Immune-related endocrine adverse events occur in up to one third of patients
      treated with immune checkpoint inhibitors. The purpose of this article is to
      provide a comprehensive review of the multimodality imaging features of the
      different immune-related endocrine adverse events. In this article, we will
      introduce the different types of immune checkpoint inhibitors used in clinical
      practice, and for each endocrine organ affected we will describe the clinical
      presentation, the multimodality imaging features at presentation and after
      treatment, and the possible differential diagnosis.

PMID- 29348052
TI  - Thirty-day complication rate of percutaneous gastrojejunostomy and gastrostomy
      tube insertion using a single-puncture, dual-anchor technique.
AB  - PURPOSE: Our objective was to assess 30-day mortality and complication rates
      associated with percutaneous enteral feeding tube insertion using a single
      puncture, dual-suture anchor gastropexy and peel-away sheath technique. We
      explored differences in complications based on indication and gastrostomy versus
      gastrojejunostomy tube. METHODS: A retrospective review was conducted of adult
      patients undergoing fluoroscopically guided gastrojejunostomy (GJ) and
      gastrostomy (G) tube insertions between July 2011 and 2014 by five interventional
      radiologists at a single tertiary care centre. A single-puncture dual-anchor
      gastropexy technique with a peel-away sheath was used for all patients.
      Complications within 30 day post-procedure were classified based on the Society
      of Interventional Radiology Standards of Practice for Gastrointestinal Access.
      Procedure-related mortality and complication rates, as well as indication
      specific complication rates, were compared between GJ and G groups. RESULTS: 559
      consecutive patients underwent G (86) or GJ (473) tube insertion. Primary
      technical success was 100%. Nine major (1.6%) and 60 minor (10.7%) complications
      occurred for an overall complication rate of 12.3%. The 30-day complication rate
      was significantly higher for GJ compared to G tube insertion (13.5% v. 5.8%, p =
      .049). There was a trend toward a higher 30-day minor complication rate for the
      GJ group (11.8% v. 4.7%, p = .057), but no significant difference between groups
      with respect to major complications (1.7% v. 1.2%, p = 1.0). Four procedure
      related deaths occurred resulting in an overall procedure-related mortality of
      0.7%. No significant difference in the procedure-related mortality was found
      between GJ and G groups (0.6% v. 1.2%, p = .49). CONCLUSION: The 30-day major
      complication and procedure-related mortality rates from G and GJ tube insertion
      are low when using a single-puncture, dual-anchor gastropexy technique. GJ tube
      insertion is associated with a higher overall complication rate, likely due to
      more minor complications, but may avoid long-term adverse events.

PMID- 29348054
TI  - Evaluation of sulfane sulfur bioeffects via a mitochondria-targeting selenium
      containing near-infrared fluorescent probe.
AB  - As a crucial member in antioxidant regulatory systems, sulfane sulfur plays
      essential roles in cytoprotective mechanisms by directly eliminating ROS and
      altering ROS-mediated redox signaling. Despite the rising interests in sulfane
      sulfur, there only a few bio-compatible methods are available for its direct
      detection. Moreover, most of the existing methods cannot meet the requirements of
      real-time detection due to the reactive and labile chemical properties of sulfane
      sulfur. Therefore, we strive to clarify the mutual relationship between
      mitochondria sulfane sulfur and ROS under hypoxia stress. Herein, we report a
      near-infrared fluorescent probe Mito-SeH for the selective imaging of
      mitochondrial sulfane sulfur in cells and in vivo under hypoxia stress. Mito-SeH
      includes three moieties: a selenol group (SeH) as the stronger sulfur-acceptor; a
      near-infrared azo-BODIPY fluorophore as the fluorescent modulator; a lipophilic
      alkyltriphenylphosphonium cation as the mitochondrial delivery. Mito-SeH exhibits
      excellent selectivity and sensitivity towards the detection of mitochondria
      sulfane sulfur. The hypoxia response behavior of Mito-SeH is evaluated in
      monolayer cell and three-dimensional multicellular spheroid to clarify the
      relationship between sulfane sulfur and hypoxia. We confirm that sulfane sulfur
      protection mechanism against hypoxia is to inhibition of caspase-dependent
      apoptosis through directly scavenging ROS pathway. The probe is also applied to
      measurement of sulfane sulfur in ex vivo-dissected organs of hypoxic mouse model,
      as well as the probe is successfully used for real-time monitoring the changes of
      sulfane sulfur and ROS in acute ischemia mice model. We suggest that sulfane
      sulfur may be a novel therapeutic agent for hypoxia-induced injury.

PMID- 29348055
TI  - High-resolution structures of mitochondrial ribosomes and their functional
      implications.
AB  - Mitochondrial ribosomes (mitoribosomes) almost exclusively synthesize essential
      components of the oxidative phosphorylation machinery. Dysfunction of
      mitochondrial protein biosynthesis leads to human diseases and plays an important
      role in the altered metabolism of cancer cells. Recent developments in cryo
      electron microscopy enabled the structural characterization of complete yeast and
      mammalian mitoribosomes at near-atomic resolution. Despite originating from
      ancestral bacterial ribosomes, mitoribosomes have diverged in their composition
      and architecture. Mitoribosomal proteins are larger and more numerous, forming an
      extended network around the ribosomal RNA, which is expanded in yeast and highly
      reduced in mammals. Novel protein elements at the entrance or exit of the mRNA
      channel imply a different mechanism of mRNA recruitment. The polypeptide tunnel
      is optimized for the synthesis of hydrophobic proteins and their co-translational
      membrane insertion.

PMID- 29348056
TI  - Achieving local and global shared realities: distance guides alignment to
      specific or general social influences.
AB  - Humans routinely navigate a multitude of potential social influences, ranging
      from specific individual's opinions to general social norms and group values.
      Whereas specific social influences afford opportunities to achieve shared inner
      states with particular individuals, general social influences afford
      opportunities to achieve shared inner states with broader groups. We review
      recent theory and evidence examining how people tune into different kinds of
      social influence in the service of shared reality. We argue that the distance of
      an attitude object (e.g. how far away it is in time or space) systematically
      influences what kind of social influence informs people's attitudes. As an
      attitude object grows more distant, people's attitudes increasingly align with
      general (vs. specific) social influences.

PMID- 29348057
TI  - Peanut straw biochar increases the resistance of two Ultisols derived from
      different parent materials to acidification: A mechanism study.
AB  - The mechanisms for increasing soil pH buffering capacity (pHBC) and soil
      resistance to acidification by peanut straw biochar were investigated by
      undertaking indoor incubation and simulated acidification experiments using two
      Ultisols derived from tertiary red sandstone and quaternary red earth. The
      biochar increased the pHBC and resistance of the two Ultisols to acidification.
      The addition of 3% biochar increased the pHBC of the two Ultisols by 76% and 25%,
      respectively. The increased resistance of the soils to acidification led to the
      inhibition to decrease in soil pH and the activation of soil Al during
      acidification. The protonation of carboxyl groups on the biochar surface was the
      main mechanism responsible for resisting acidification of the Ultisols when the
      pH was between 4.5 and 7.0. The higher soil pH (>6.0) after biochar application
      and the large number of carboxyl groups on the biochar surface were essential if
      biochar was to significantly increase the resistance of soils to acidification.

PMID- 29348058
TI  - Elemental assessment of vegetation via portable X-ray fluorescence (PXRF)
      spectrometry.
AB  - Elemental concentrations in vegetation are of critical importance, whether
      establishing plant essential element concentrations (toxicity vs. deficiency) or
      investigating deleterious elements (e.g., heavy metals) differentially extracted
      from the soil by plants. Traditionally, elemental analysis of vegetation has been
      facilitated by acid digestion followed by quantification via inductively coupled
      plasma (ICP) or atomic absorption (AA) spectroscopy. Previous studies have
      utilized portable X-ray fluorescence (PXRF) spectroscopy to quantify elements in
      soils, but few have evaluated the vegetation. In this study, a PXRF spectrometer
      was employed to scan 228 organic material samples (thatch, deciduous leaves,
      grasses, tree bark, and herbaceous plants) from smelter-impacted areas of
      Romania, as well as National Institute of Standards and Technology (NIST)
      certified reference materials, to demonstrate the application of PXRF for
      elemental determination in vegetation. Samples were scanned in three conditions:
      as received from the field (moist), oven dry (70  degrees C), and dried and
      powdered to pass a 2 mm sieve. Performance metrics of PXRF models relative to ICP
      atomic emission spectroscopy were developed to asses optimal scanning conditions.
      Thatch and bark samples showed the highest mean PXRF and ICP concentrations
      (e.g., Zn, Pb, Cd, Fe), with the exceptions of K and Cl. Validation statistics
      indicate that the stable validation predictive capacity of PXRF increased in the
      following order: oven dry intact < field moist < oven dried and powdered. Even
      under field moist conditions, PXRF could reasonably be used for the determination
      of Zn (coefficient of determination, R2val 0.86; residual prediction deviation,
      RPD 2.72) and Cu (R2val 0.77; RPD 2.12), while dried and powdered samples allowed
      for stable validation prediction of Pb (R2val 0.90; RPD 3.29), Fe (R2val 0.80;
      RPD 2.29), Cd (R2val 0.75; RPD 2.07) and Cu (R2val 0.98; RPD of 8.53). Summarily,
      PXRF was shown to be a useful approach for quickly assessing the elemental
      concentration in vegetation. Future PXRF/vegetation research should explore
      additional elements and investigate its usefulness in evaluating phytoremediation
      effectiveness.

PMID- 29348059
TI  - Synthesis and evaluation of a superabsorbent-fertilizer composite for maximizing
      the nutrient and water use efficiency in forestry plantations.
AB  - Reducing fertilizer use is a priority in the quest for sustainable forestry
      systems. In short rotation Eucalyptus plantations, NPK pellets are routinely
      added to the seedling's top soil layer at planting, potentially leading to
      increased seedling mortality, nutrient loss and environmental degradation. To
      address this triple challenge, the development of efficient fertilization
      practices is essential. In the present work, we synthesized a crosslinked acrylic
      cellulosic superabsorbent composite (SAPH-BAL) containing small amounts of
      specific nutrients integrated in the polymer matrix. We analyzed the composite's
      chemical and rheological properties, and assessed the viability of Eucalyptus
      plantations supplied with it at planting. Physiological measurements confirmed
      the suitability of SAPH-BAL in greenhouse-grown potted seedlings subjected to
      different growth conditions, showing that it efficiently delivers nutrients while
      protecting seedlings from drought stress. Field experiments carried out at ten
      South American locations covering an ample range of environmental conditions
      confirmed the beneficial effect of SAPH-BAL on growth and survival in comparison
      to the conventional fertilization scheme (superabsorbent + 75 g NPK).
      Furthermore, it was found that plants treated with SAPH-BAL were less affected by
      the differences in rainfall regimes during the experiments compared to those
      fertilized conventionally. To the best of our knowledge this is the first report
      describing the successful use of superabsorbents for root targeted delivery of
      fertilizers in forestry operations.

PMID- 29348060
TI  - Exposure to workplace smoking bans and continuity of daily smoking patterns on
      workdays and weekends.
AB  - INTRODUCTION: Individuals may compensate for workplace smoking bans by smoking
      more before or after work, or escaping bans to smoke, but no studies have
      conducted a detailed, quantitative analysis of such compensatory behaviors using
      real-time data. METHODS: 124 daily smokers documented smoking occasions over
      3weeks using ecological momentary assessment (EMA), and provided information on
      real-world exposure to smoking restrictions and type of workplace smoking policy
      (full, partial, or no bans). Mixed modeling and generalized estimating equations
      assessed effects of time of day, weekday (vs weekend), and workplace policy on
      mean cigarettes per hour (CPH) and reports of changing location to smoke.
      RESULTS: Individuals were most likely to change locations to smoke during
      business hours, regardless of work policy, and frequency of EMA reports of
      restrictions at work was associated with increased likelihood of changing
      locations to smoke (OR=1.11, 95% CI 1.05-1.16; p<0.0001). Workplace smoking
      policy, time block, and weekday/weekend interacted to predict CPH (p<0.01), such
      that individuals with partial work bans -but not those with full bans - smoked
      more at night (9pm - bed) on weekdays compared to weekends. CONCLUSIONS: There
      was little evidence that full bans interfered with subjects' smoking during
      business hours across weekdays and weekends. Smokers largely compensate for
      exposure to workplace smoking bans by escaping restrictions during business
      hours. Better understanding the effects of smoking bans on smoking behavior may
      help to improve their effectiveness and yield insights into determinants of
      smoking in more restrictive environments.

PMID- 29348061
TI  - Effects of wavelength mixing ratio and photoperiod on microalgal biomass and
      lipid production in a two-phase culture system using LED illumination.
AB  - Blue and red light-emitting diodes (LEDs) were used to study the effects of
      wavelength mixing ratios, photoperiod regimes, and green wavelength stress on
      Nannochloropsis salina, Isochrysis galbana, and Phaeodactylum tricornutum cell
      biomass and lipid production. The maximum specific growth rates of I. galbana and
      P. tricornutum were obtained under a 50:50 mixing ratio of blue and red
      wavelength LEDs; that of N. salina was obtained under red LED. Maximum cell
      biomass for N. salina and P. tricornutum was 0.75 and 1.07 g dcw/L, respectively,
      obtained under a 24:0 h light/dark cycle. However, the maximum I. galbana biomass
      was 0.89 g dcw/L under an 18:6 h light/dark cycle. The maximum lipid contents for
      N. salina, I. galbana, and P. tricornutum were 49.4, 63.3 and 62.0% (w/w),
      respectively, after exposure to green LED. Eicosapentaenoic acid (EPA) and
      docosahexaenoic acid (DHA) were obtained 1% in P. tricornutum and 2% in I.
      galbana.

PMID- 29348062
TI  - Improving sewage sludge composting by addition of spent mushroom substrate and
      sucrose.
AB  - The effects of spent mushroom substrate (SMS) and sucrose (S) amendment on
      emissions of nitrogenous gas (mainly NH3 and N2O) and end products quality of
      sewage sludge (SS) composting were evaluated. Five treatments were composted for
      20 days in laboratory-scale using SS with different dosages of SMS and S, without
      additive amended treatment used as control. The results indicated that SMS
      amendments especially combination with S promoted dehydrogenase activity, CO2
      production, organic matter degradation and humification in the composting, and
      maturity indices of composting also showed that the 30%SMS+2%S treatment could be
      much more appropriate to improve the composting process, such as total Kjeldahl
      nitrogen, nitrification index, humic acids/fulvic acids ratio and germination
      index, while the emissions of NH3 and N2O were reduced by 34.1% and 86.2%,
      respectively. These results shown that the moderate addition of SMS and S could
      improve the compost maturity and reduce nitrogenous gas emission.

PMID- 29348063
TI  - Production of acids and alcohols from syngas in a two-stage continuous
      fermentation process.
AB  - A two-stage continuous system with two stirred tank reactors in series was
      utilized to perform syngas fermentation using Clostridium carboxidivorans. The
      first bioreactor (bioreactor 1) was maintained at pH 6 to promote acidogenesis
      and the second one (bioreactor 2) at pH 5 to stimulate solventogenesis. Both
      reactors were operated in continuous mode by feeding syngas (CO:CO2:H2:N2;
      30:10:20:40; vol%) at a constant flow rate while supplying a nutrient medium at
      different flow rates of 8.1, 15, 22 and 30 ml/h. A cell recycling unit was added
      to bioreactor 2 in order to recycle the cells back to the reactor, maintaining
      the OD600 around 1 in bioreactor 2 throughout the experimental run. When
      comparing the flow rates, the best results in terms of solvent production were
      obtained with a flow rate of 22 ml/h, reaching the highest average outlet
      concentration for alcohols (1.51 g/L) and the most favorable alcohol/acid ratio
      of 0.32.

PMID- 29348064
TI  - Magnetic mapping of distribution of wood ash used for fertilization of forest
      soil.
AB  - The effect of wood-ash fertilization on forest soils has been assessed mainly
      through geochemical methods (e.g., content of soil organic matter or nutrients).
      However, a simple and fast method of determining the distribution of the ash and
      the extent of affected soil is missing. In this study we present the use of
      magnetic susceptibility, which is controlled by Fe-oxides, in comparing the
      fertilized soil in the forest plantation of pine and oak with intact forest soil.
      Spatial and vertical distribution of magnetic susceptibility was measured in an
      oak and pine plantation next to stems of young plants, where wood ash was applied
      as fertilizer. Pattern of the susceptibility distribution was compared with that
      in non-fertilized part of the plantation as well as with a spot of intact natural
      forest soil nearby. Our results show that the wood-ash samples contain
      significant amount of ferrimagnetic magnetite with susceptibility higher than
      that of typical forest soil. Clear differences were observed between magnetic
      susceptibility of furrows and ridges. Moreover, the dispersed ash remains
      practically on the surface, does not penetrate to deeper layers. Finally, our
      data suggest significant differences in surface values between the pine and oak
      plants. Based on this study we may conclude that magnetic susceptibility may
      represent a simple and approximate method of assessing the extent of soil
      affected by wood-ash.

PMID- 29348065
TI  - The behaviour of 236U in the North Atlantic Ocean assessed from numerical
      modelling: A new evaluation of the input function into the Arctic.
AB  - A numerical model, previously validated with other radionuclides, was applied to
      simulate the dispersion of 236U released from European nuclear fuel reprocessing
      plants in the North Atlantic and Shelf Seas using a published reconstruction of
      Sellafield and La Hague releases. Model results are in better agreement with
      observations if the lowest estimation of such releases are used. This implies
      that approximately 40kg of 236U has been discharged from Sellafield. It was found
      that adsorption of 236U on bed sediments of the shallow European Shelf Seas plays
      an essential role in its dispersion patterns. This contrasts strongly with the
      more conservative behaviour of 129I in the same area. This has two important
      implications in the use of 236U as oceanographic tracer; i) special care must be
      taken in coastal areas, as sediments might act as sinks and sources of 236U; ii)
      the annual input function of 236U into the Arctic is not directly controlled by
      the annual discharges from Sellafield and La Hague, since sediments from the
      Irish, Celtic and North Sea modulate and smooth the signal. Only 52% of the total
      releases enter into the Arctic Ocean.

PMID- 29348066
TI  - Multi-scale measurements show limited soil greenhouse gas emissions in Kenyan
      smallholder coffee-dairy systems.
AB  - Efforts have been made in recent years to improve knowledge about soil greenhouse
      gas (GHG) fluxes from sub-Saharan Africa. However, data on soil GHG emissions
      from smallholder coffee-dairy systems have not hitherto been measured
      experimentally. This study aimed to quantify soil GHG emissions at different
      spatial and temporal scales in smallholder coffee-dairy farms in Murang'a County,
      Central Kenya. GHG measurements were carried out for one year, comprising two
      cropping seasons, using vented static chambers and gas chromatography. Sixty
      rectangular frames were installed on two farms comprising the three main cropping
      systems found in the area: 1) coffee (Coffea arabica L.); 2) Napier grass
      (Pennisetum purpureum); and 3) maize intercropped with beans (Zea mays and
      Phaseolus vulgaris). Within these fields, chambers were allocated on fertilised
      and unfertilised locations to capture spatial variability. Cumulative annual
      fluxes in coffee plots ranged from 1 to 1.9kgN2O-Nha-1, 6.5 to 7.6MgCO2-Cha-1 and
      -3.4 to -2.2kgCH4-Cha-1, with 66% to 94% of annual GHG fluxes occurring during
      rainy seasons. Across the farm plots, coffee received most of the N inputs and
      had 56% to 89% higher emissions of N2O than Napier grass, maize and beans. Within
      farm plots, two to six times higher emissions were found in fertilised hotspots -
      around the perimeter of coffee trees or within planted maize rows - than in
      unfertilised locations between trees, rows and planting holes. Background and
      induced soil N2O emissions from fertiliser and manure applications in the three
      cropping systems were lower than hypothesized from previous studies and empirical
      models. This study supplements methods and underlying data for the quantification
      of GHG emissions at multiple spatial and temporal scales in tropical, smallholder
      farming systems. Advances towards overcoming the dearth of data will facilitate
      the understanding of synergies and tradeoffs of climate-smart approaches for low
      emissions development.

PMID- 29348067
TI  - Physiological response and transcription profiling analysis reveals the role of
      H2S in alleviating excess nitrate stress tolerance in tomato roots.
AB  - Soil secondary salinization caused by excess nitrate addition is one of the major
      obstacles in greenhouse vegetable production. Excess nitrate inhibited the growth
      of tomato plants, while application of 100 MUM H2S donor NaHS efficiently
      increased the plant height, fresh and dry weight of shoot and root, root length,
      endogenous H2S contents and L-cysteine desulfhydrases activities. NaHS altered
      the oxidative status of nitrate-stressed plants as inferred by changes in
      reactive oxygen species (ROS) accumulation and lipid peroxidation accompanied by
      regulation of the activities of superoxide dismutase (SOD), peroxidase (POD),
      catalase (CAT), ascorbate peroxidase (APX). Besides, NaHS increased the nitric
      oxide (NO) and total S-nitrosothiols (SNOs) contents, nitrate reductase (NR)
      activities and decreased the S-nitrosoglutathione reductase (GSNOR) activities
      under nitrate stress. Furthermore, microarray analysis using the Affymetrix
      Tomato GeneChip showed that 5349 transcripts were up-regulated and 5536
      transcripts were down-regulated under NaHS and excess nitrate stress treatment,
      compared to the excess nitrate stress alone. The differentially expressed genes
      (log2 fold change >2 or <  -2) of up-regulated (213) and down-regulated (271)
      genes identified were functionally annotated and subsequently classified into 9
      functional categories. These categories included metabolism, signal transduction,
      defence response, transcription factor, protein synthesis and protein fate,
      transporter, cell wall related, hormone response, cell death, energy and unknown
      proteins. Our study suggested exogenous NaHS might enhance excess nitrate stress
      tolerance of tomato plants by modulating ROS and reactive nitrogen species (RNS)
      signaling and downstream transcriptional adjustment, such as defence response,
      signal transduction and transcription factors.

PMID- 29348068
TI  - Advantages of titanium xerogel over titanium tetrachloride and polytitanium
      tetrachloride in coagulation: A mechanism analysis.
AB  - Titanium xerogel coagulant (TXC) worked better than titanium tetrachloride (TC)
      and polytitanium chloride (PTC) in a wider pH/dose range for the removal of
      turbidity. However, the underlying mechanisms were not comprehensively
      understood. In this work, the better coagulation performance of TXC than TC and
      PTC was systematically elucidated from the following aspects: the physicochemical
      properties of the three coagulants, the removal of turbidity and organic matter,
      and the complexation reactions in coagulation. The results demonstrate that the
      merits of TXC were attributable to the following characteristics: (1) the higher
      surface charge density/total surface site concentration/isoelectric point of TXC
      hydrolysates, (2) the formation of TXC hydrolysates with a net-work structure,
      and (3) the strong binding affinity of TXC hydrolysates to organic matter caused
      by the bonded acetylacetone in the TXC framework. In short, the hydrolysis
      behavior of TXC significantly differed from both its precursor, TC, and the
      prehydrolyzed PTC. The difference in the hydrolysis of TXC was derived from the
      gelation process, which led to the polymerization of Ti in a way different from
      prehydrolyzation. The elucidation of the hydrolysis mechanisms is useful for the
      better application of Ti-based coagulants and may shed light on the preparation
      of other metal salts.

PMID- 29348069
TI  - Thermomechanical processing of In-containing beta-type Ti-Nb alloys.
AB  - In this study, the effect of thermomechanical processing on microstructure
      evolution of the indium-containing beta-type Ti alloys (Ti-40Nb)-3.5In and (Ti
      36Nb)-3.5In was examined. Both alloys show an increased beta-phase stability
      compared to binary alloys due to In additions. This leads to a reduced alpha''
      phase fraction in the solution treated and recrystallized state in the case of
      (Ti-36Nb)-3.5In and to the suppression of stress-induced alpha'' formation and
      deformation twinning for (Ti-40Nb)-3.5In. The mechanical properties of the alloys
      were subsequently studied by quasistatic tensile tests in the recrystallized
      state, revealing reduced Young's modulus values of 58GPa ((Ti-40Nb)-3.5In) and
      56GPa ((Ti-36Nb)-3.5In) compared to 60GPa as determined for Ti-40Nb. For both In
      containing alloys the ultimate tensile strength is in the range of 560MPa. Due to
      the suppressed alpha'' formation, (Ti-40Nb)-3.5In exhibits a linear elastic
      deformation behavior during tensile loading together with a low Young's modulus
      and is therefore promising for load-bearing implants.

PMID- 29348070
TI  - Rational approach to highly potent and selective apoptosis signal-regulating
      kinase 1 (ASK1) inhibitors.
AB  - Many diseases are believed to be driven by pathological levels of reactive oxygen
      species (ROS) and oxidative stress has long been recognized as a driver for
      inflammatory disorders. Apoptosis signal-regulating kinase 1 (ASK1) has been
      reported to be activated by intracellular ROS and its inhibition leads to a down
      regulation of p38-and JNK-dependent signaling. Consequently, ASK1 inhibitors may
      have the potential to treat clinically important inflammatory pathologies
      including renal, pulmonary and liver diseases. Analysis of the ASK1 ATP-binding
      site suggested that Gln756, an amino acid that rarely occurs at the GK+2
      position, offered opportunities for achieving kinase selectivity for ASK1 which
      was applied to the design of a parallel medicinal chemistry library that afforded
      inhibitors of ASK1 with nanomolar potency and excellent kinome selectivity. A
      focused optimization strategy utilizing structure-based design resulted in the
      identification of ASK1 inhibitors with low nanomolar potency in a cellular assay,
      high selectivity when tested against kinase and broad pharmacology screening
      panels, and attractive physicochemical properties. The compounds we describe are
      attractive tool compounds to inform the therapeutic potential of ASK1 inhibition.

PMID- 29348071
TI  - A focused fragment library targeting the antibiotic resistance enzyme -
      Oxacillinase-48: Synthesis, structural evaluation and inhibitor design.
AB  - beta-Lactam antibiotics are of utmost importance when treating bacterial
      infections in the medical community. However, currently their utility is
      threatened by the emergence and spread of beta-lactam resistance. The most
      prevalent resistance mechanism to beta-lactam antibiotics is expression of beta
      lactamase enzymes. One way to overcome resistance caused by beta-lactamases, is
      the development of beta-lactamase inhibitors and today several beta-lactamase
      inhibitors e.g. avibactam, are approved in the clinic. Our focus is the
      oxacillinase-48 (OXA-48), an enzyme reported to spread rapidly across the world
      and commonly identified in Escherichia coli and Klebsiella pneumoniae. To guide
      inhibitor design, we used diversely substituted 3-aryl and 3-heteroaryl benzoic
      acids to probe the active site of OXA-48 for useful enzyme-inhibitor
      interactions. In the presented study, a focused fragment library containing 49 3
      substituted benzoic acid derivatives were synthesised and biochemically
      characterized. Based on crystallographic data from 33 fragment-enzyme complexes,
      the fragments could be classified into R1 or R2 binders by their overall binding
      conformation in relation to the binding of the R1 and R2 side groups of imipenem.
      Moreover, binding interactions attractive for future inhibitor design were found
      and their usefulness explored by the rational design and evaluation of merged
      inhibitors from orthogonally binding fragments. The best inhibitors among the
      resulting 3,5-disubstituted benzoic acids showed inhibitory potential in the low
      micromolar range (IC50 = 2.9 MUM). For these inhibitors, the complex X-ray
      structures revealed non-covalent binding to Arg250, Arg214 and Tyr211 in the
      active site and the interactions observed with the mono-substituted fragments
      were also identified in the merged structures.

PMID- 29348072
TI  - Structure-based development of an osteoprotegerin-like glycopeptide that blocks
      RANKL/RANK interactions and reduces ovariectomy-induced bone loss in mice.
AB  - Osteoporosis is a metabolic bone disease characterized by low bone mass and micro
      architectural deterioration of bone, for which the underlying mechanism is an
      imbalance between bone resorption and bone remodeling. The protein-protein
      interactions between receptor activator of nuclear factor-kappaB ligand (RANKL),
      RANK (its receptor), and osteoprotegerin (OPG), are known to mediate the
      development and activation of osteoclasts in bone remodeling, and are regarded as
      a pivotal therapeutic target for the treatment of osteoporosis. Herein, we
      disclose the successful development of a novel glycopeptide (OM-2), the structure
      of which is based on the key interacting sites of the reported RANKL and OPG
      crystal structure. OM-2 exhibited potent binding affinity with RANKL and
      resistance to degradation by protease enzymes. It also blocked RANKL/RANK
      interactions, and inhibited osteoclastogenesis in vitro. In vivo studies
      confirmed that OM-2 could effectively reduce bone loss and inhibit osteoclast
      activation in ovariectomized (OVX) mice at a dosage of 20.0 mg/kg/day.
      Accordingly, OM-2 is suggested as a therapeutic candidate for postmenopausal
      osteoporosis (PMOP) and osteoclastogenesis-related diseases like rheumatoid
      arthritis (RA). More importantly, its identification validates our structure
      based strategy for the development of drugs that target the RANKL/RANK/OPG
      system.

PMID- 29348073
TI  - Rate of switch from bipolar depression into mania after morning light therapy: A
      historical review.
AB  - Light therapy (LT) is efficacious for bipolar depression with effect sizes
      equivalent to those in antidepressant pharmacotherapy trials. Patients with
      bipolar disorder (BD) show a 15-40% rate of manic switches during antidepressant
      drug treatment. The rate of manic switches during LT has never been estimated. We
      searched all the literature studies reporting effects of antidepressant LT in BD.
      41 studies described 799 patients with BD treated with antidepressant LT, from
      among which 7 (0.9%) switched into mania and 11 (1.4%) switched into hypomania.
      The method of assessment of treatment-emergent symptoms significantly influenced
      the detection of switches into mania: 0% when no method was reported, 0.8% with
      clinical mental state examination, and 3% with rating scales (chi2 = 14.805, d.f.
      4, p = 0.005). The rate of switch increased to 18.8% when considering the 16
      patients with rapid-cycling BD. Switches occurred independent of treatment
      modality (light intensity, duration, and circadian timing of administration). The
      available literature shows that the highest reported rate of switch from bipolar
      depression into mania after LT is closely similar to the 4% switch rate expected
      during the placebo treatment of BD, thus not justifying specific concerns when
      using this treatment option.

PMID- 29348074
TI  - Standardized medical image registration for radiological identification of
      decedents based on paranasal sinuses.
AB  - Image registration software is frequently used in clinical radiology, e.g., for
      follow-up diagnosis. To a certain extent, the radiological identification of
      decedents (RadID) is comparable to a clinical follow-up diagnosis, in that two
      datasets from different dates are compared in terms of their anatomical
      characteristics (e.g., paranasal sinuses) or surgical implants. Due to the
      increasing use of computed tomography (CT) for head examinations in clinical
      radiology and the increased use of postmortem CT (PMCT) in forensic imaging, the
      comparison of three-dimensional (3D) clinical CT (termed as antemortem CT (AMCT)
      in this article) and PMCT datasets for RadID is becoming increasingly practical.
      In particular, the comparison of paranasal sinuses in AMCT and PMCT imaging is
      considered a suitable and reliable modality for RadID. However, previous
      publications regarding RadID based on comparisons of 3D datasets have not
      considered the implementation of image registration to provide software-side
      support for RadID. This article demonstrates and evaluates the use of a standard
      medical image registration procedure for RadID by comparing paranasal sinuses.

PMID- 29348076
TI  - Association between serum arsenic levels and gestational diabetes mellitus: A
      population-based birth cohort study.
AB  - Gestational diabetes mellitus (GDM) is a common obstetric complication with
      adverse effects on both mothers and their children. Previous studies revealed the
      link between Arsenic (As) exposure and incidence of diabetes mellitus (DM), but
      the data on the association between maternal As exposure and GDM is scarce. We
      examined this association among a population-based birth cohort. As
      concentrations were determined at multiple time points during pregnancy by ICP
      MS. The association between As levels and GDM prevalence was examined using
      logistic regression model after adjustment for confounders. A total of 419
      (12.85%) women were diagnosed with GDM. The incidences of GDM gradually increased
      with increasing quartiles of As levels with significant trend. As levels were
      associated with the GDM (95%CI: 1.29-2.43) at only the 4th quartile in the first
      trimester. After adjustment for maternal age, prepregnancy body mass index (BMI),
      monthly income, gestational age and parity, the association remains significant
      (95%CI: 1.22-2.38). Stratified analyses showed the associations were largely
      limited to normal maternal age (95%CI: 1.19-3.04) and normal weight women (95%CI:
      1.18-2.66). Our study showed an association between As and GDM in a birth cohort
      and explored first trimester may be the critical period for As associated GDM.
      This association was universal in the general pregnant population of normal age
      and of normal weight.

PMID- 29348075
TI  - Benzalkonium chloride, benzethonium chloride, and chloroxylenol - Three
      replacement antimicrobials are more toxic than triclosan and triclocarban in two
      model organisms.
AB  - With the recent ban of triclosan (TCS) and triclocarban (TCC) from some personal
      care products, many replacement antimicrobial compounds have been used. Yet the
      potential health risk and environmental impact of these replacement compounds are
      largely unknown. Here we investigated the toxicological effects of three commonly
      used replacement antimicrobials, benzalkonium chloride (BAC), benzethonium
      chloride (BEC), and chloroxylenol (CX) to two model organisms, the nematode C.
      elegans and zebrafish (Danio rerio), and compared them to the banned TCS and TCC.
      We found that these replacement compounds are not any safer than the banned
      antimicrobials. In the worm, at least one of the three, BAC, showed comparable
      toxicity to TCS from organismal to molecular levels, with toxic effects occurring
      at lower hundred MUg/L to lower mg/L levels. In the fish, all three compounds at
      the tested concentration ranges (0.05-5 mg/L) showed toxicity effects to
      zebrafish embryos, indicated by hatching delay or inhibition, embryonic
      mortality, morphological malformations, and neurotoxicity. BAC was the most toxic
      among the three, with acute lethal toxicity occurring at environmentally relevant
      concentrations (hundreds of MUg/L), which is comparable to the banned TCC.
      However, the toxicity effects of BAC and TCC occurred within different time
      windows, potentially suggesting different mechanisms of toxicity. CX was the only
      compound that induced a "body curvature" phenotype among the five compounds
      examined, suggesting a unique mode of toxic action for this compound.
      Furthermore, all five compounds except TCS induced neurotoxicity in fish larvae,
      indicated by alterations in secondary motoneuron axonal projections. Such
      neurotoxicity has been largely understudied for these antimicrobials in the past
      years and calls for further investigations in terms of its underlying mechanisms
      and ecological significance. These findings strongly indicate that scrutiny
      should be put on these replacement compounds before their introduction into
      massive use in personal care products.

PMID- 29348077
TI  - Effects of Cordyceps sinensis on macrophage function in high-fat diet fed rats
      and its anti-proliferative effects on IMR-32 human neuroblastoma cells.
AB  - Macrophages have been considered an elusive yet emerging therapeutic target in
      tumor development since they are an important component in tumor
      microenvironment. The purpose of the present study was to evaluate the effect of
      C. sinensis on macrophage function (a component of tumor microenvironment which
      can alter the virulence of cancer) in high-fat diet fed rats. IMR-32 human
      neuroblastoma cell cytotoxicity was also investigated. The following parameters
      were observed to evaluate macrophage function: superoxide anion, hydrogen
      peroxide, nitric oxide, lysosomal volume and phagocytic capacity. High fat diet
      (HFD) plus C. sinensis supplementation promoted a decreased superoxide anion and
      hydrogen peroxide levels as well as lysosomal volume and phagocytic capacity.
      Nitric oxide was increased in the same group. In summary, C. sinensis offered an
      important anti-tumoral perspective from the standpoint of the tumor
      microenvironment and in vitro IMR-32 cytotoxicity.

PMID- 29348078
TI  - A clinical study showing altered antioxidants profile in patients with
      hypertension.
AB  - We compared the plasma antioxidants level of normal control group with that of
      hypertensive patients in order to test the hypothesis "that antioxidants level
      has been diminished in hypertensive patients and that antioxidants are
      interconnected with each other making a network. The plasma and red blood cells
      antioxidants level of newly diagnosed hypertensive patients [(n=30), (mean age 53
      years), (mean systolic BP 158 mmHg, mean diastolic BP 100 mmHg)] were compared to
      those of the control subjects [(n=30), (mean age 50 years), (mean systolic BP 126
      mmHg, mean diastolic BP 90 mmHg)] using liquid chromatography linked with
      electrochemical detector (HPLC-ECD). The data was analyzed by Minitab software at
      a 95% confidence interval (p<0.05) as significant. The comparison between the two
      groups was made applying 2-sample and paired t-test. The individual concentration
      of antioxidants in both plasma and red blood cells of hypertensive patients was
      lower in comparison with that of control group while the oxidized/reduced ratios
      of these antioxidants were higher in hypertensive patients in comparison with
      that of control group. It is concluded that antioxidants level had been
      diminished in the hypertensive patients when compared with control group. The
      overall concentration of all antioxidants has been diminished in the oxidative
      stress induced pathological conditions which confirm that the studied
      antioxidants are working in a network. This study may be helpful for the
      recommendation of antioxidants intervention.

PMID- 29348079
TI  - Synthesis, optimization and biological evaluation of 99mTc-digoxin as possible
      cardiac imaging agent.
AB  - Heart imaging radiopharmaceuticals could improve the diagnostic value of routine
      heart scanning for detecting cardiac disorders. The aim of the study was to
      prepare high radiochemical purity 99mTc-Digoxin in a yield of about 98%. The
      optimal conditions for labelling were as follows: 100MUg of Digoxin, 2MUg of
      SnCl<inf>2</inf>*2H<inf>2</inf>O, room temperature (25+/-1 degrees C), reaction
      retention time of 30 min at pH 7. Under these conditions, the radiochemical yield
      of <sup>99m</sup>Tc-Digoxin reaches 98%. In vivo bio distribution was performed
      in normal Swiss Albino mice at different time intervals after administration of
      <sup>99m</sup>Tc-Digoxin.Scintigraphic study of <sup>99m</sup>Tc-Digoxin was
      performed in rabbits. The heart uptake of <sup>99m</sup>Tc-Digoxin was
      sufficiently high and thus may be a potential myocardial imaging
      radiopharmaceutical applicable in cardiology.

PMID- 29348080
TI  - Squid ink polysaccharide prevents chemotherapy induced injury in the testes of
      reproducing mice.
AB  - The present study was conducted to investigate the preventive effects of squid
      ink polysaccharides (SIP) on the damage of sperm and reproduction induced by
      cyclophosphamide that is most commonly used for treating clinically cancers. Male
      Kunming mice exposed to cyclophosphamide were administered with SIP and were
      sacrificed to determine sperm parameters, testicular antioxidant ability and
      reproductive capacity. Data indicated that cyclophosphamide caused obvious
      changes in mice such as significant reduction (P<0.01) of glutathione reductase
      activity (GR), vitamin C (Vc) content and total antioxidant capacity (T-AOC) in
      the testes, as well as elevation (P<0.01) of abnormal rates of sperm and fetus,
      and a decrease in the total fetal count and average fetal count (P<0.01), were
      totally alleviated by SIP. From these findings it can be concluded that SIP
      decreases chemotherapeutic damage to sperm and reproduction in mice induced by
      cyclophosphamide.

PMID- 29348081
TI  - Evaluation of antioxidant and antimicrobial activities of Bergenia ciliata Sternb
      (Rhizome) crude extract and fractions.
AB  - Biologically, screening of medicinal plants extracts have been since pre-historic
      to determine the antioxidants and antimicrobial profile. The present study was
      aimed to investigate and evaluate crude extract and different fractions of
      Bergenia ciliata Sternb (rhizome) for bioactivity which is most considerable
      medicinal plants. The chloroform fraction was found to be highly anti-oxidative
      with the IC50 value (4.15+/-0.82) as compare to ethyl acetate and n-hexane
      fraction. In addition, neither crude extract nor any fraction showed inhibition
      against fungal strains, i.e. Aspergillus flavus and Aspergillus niger.
      Furthermore, the crude extract and fractions of B. ciliata (rhizome) exhibiting
      promising activities against Bacillus atrophoeus, Bacillus subtilis, Kleibsiella
      pneumonia and Pseudomonas aeruginosa strains. In summary, B. ciliata is
      recommended as a source of bioactive compounds which might be used against
      oxidative stress and drug resistance bacteria.

PMID- 29348082
TI  - Nephrotoxic effects of Valeriana wallichii.
AB  - Aminoglycosides are the commonly used antibiotics against Gram negative bacteria.
      Their clinical applications are limited due to nephrotoxic side effects.
      Therefore, the current study was undertaken in an attempt to increase the use of
      these drugs without causing nephrotoxicity by exploring the nephroprotective
      effects of a medicinal plant with high flavonoid contents and strong antioxidant
      properties, namely Valeriana wallichii. A daily dose of 200mg/kg of the extract
      derived from V. wallichii was employed for a period of three weeks. The results
      obtained revealed that co-therapy of extract with gentamicin protected some
      changes in renal functions; however, failed to provide a complete protection as
      assessed by biochemical, physiological and histological parameters. It can be
      concluded from the current findings that V. wallichii failed to deliver
      protective effects against gentamicin induced renal damage in spite of strong
      flavonoid contents and antioxidant properties.

PMID- 29348083
TI  - GC-MS and HPLC profiles of phenolic fractions of the leaf of Telfairia
      occidentalis.
AB  - Telfairia occidentalis possesses high antioxidant activity. However, the
      antioxidant components of the plant have not yet been identified. This study was
      undertaken to identify the phenolics in the leaf of the plant. Extract and
      fractions of the leaf of the plant were analysed using the HPLC and GCMS. HPLC
      analysis revealed the presence of gallic acid (22.19MUg/mg), catechin
      (29.17MUg/mg), caffeic acid (9.17MUg/mg), ferulic acid (0.94MUg/mg), sinapic acid
      (1.91 MUg/mg) and 4-hydroxy benzoic acid (43.86 MUg/mg) in the aqueous extract.
      Phenolics fraction contained gallic acid (0.88 MUg/mg), catechin (2.70MUg/mg),
      caffeic acid (7.92MUg/mg), ferulic acid (2.72MUg/mg), benzoic acid (6.36MUg/mg),
      p-coumaric acid (1.48MUg/mg), quercetin (12.00MUg/mg). Only caffeic acid
      (2.50MUg/mg), ferulic acid (0.44MUg/mg) and quercetin (8.50MUg/mg) were detected
      in the flavonoid fraction. While GCMS analysis showed the presence of
      methylparaben; ethylparaben; benzoic acid; 4-hydroxy-2-methoxy-3,5,6-trimethyl-,
      methyl ester; 4-hydroxy-3-methoxy; phenol, 5-methoxy-2-(methoxymethyl)-; phenol,
      5-methoxy-2, 3- dimethyl; and phenol, 2-(2-benzothiazolyl)-. This study is the
      first to reveal the identity of some phenolics components of the leaf of
      Telfairia occidentalis.

PMID- 29348084
TI  - Molecular characterization of autosomal recessive non syndromic hearing loss in
      selected families from District Mardan, Pakistan.
AB  - Deafness is the most common sensory disorder, which affects 1/1000 neonates
      globally. Genetic factors are major contributors for hearing impairment. This
      study was conducted to explore the linkage of DFNB loci and their mutations with
      NSHL in selected Pakistani families. We included 10 families with history of
      deafness from district Mardan, Pakistan. Blood sample (5ml) along with personal
      and clinical information was collected from the available family members
      including both diseased and un-affected individuals. Genomic DNA was amplified
      using loci specific STR markers to investigate the linkage of DFNB loci. Family
      found linked with DFNB4 locus was screened for SLC26A4 mutations. One out of the
      ten explored families was found linked with DFNB4 locus which was further
      investigated for SLC26A4 gene mutation through direct DNA sequencing. Two novel
      mutations were observed in the studied family, one at splice donor site
      (164+2T>G) and the other at position 164+5C>G only in the affected members of the
      linked family. DFNB4 locus was found linked in the present study which harbors
      SLC26A4 gene. The novel mutation of SLC26A4 gene at the splice donor site results
      in skipping of the first coding exon and thus can lead to loss of expression of
      SLC26A4 product in the inner ear.

PMID- 29348085
TI  - Toxic effect of common poisonous plants of district Bannu, Khyber Pakhtunkhwa,
      Pakistan.
AB  - The present paper was a part of Ph.D research work, conducted during the year
      2014, in which 87 poisonous plants belonging to 54 genera, were collected,
      documented and preserved in the herbarium of Bannu, Department of Botany UST,
      Bannu Khyber Pakhtunkwa Pakistan. The plants were identified botanically,
      arranged alphabetically along with their Latin name, family name, common name,
      poisonous parts, toxicity, affects, toxin and their effects. Aim of the study was
      to induce awareness in the local people of district Bannu about the poisonous
      effects of the commonly used plants. Data about poisonous effect were collected
      from the local experienced and mostly old age people through questionnaire. Some
      information were collected from a number of veterinary texts and literature. The
      most important plants genera studied in the area were Brassica 6 species
      (11.11%), Lathyrus 5 spp (9.26%), Astragalus, Euphorbia and Prunus were with 4
      spp (7.40%). Datura, Jatropha, Ranunculus, Solanum and Sorghum were with 3 spp
      (5.56%) while Allium, Amaranthus, Chenopodium, Melilotus and Taxus were with 2
      spp (3.70%). These 15 genera contribute 48 species (55.17 %) while the remaining
      39 genera have single species each and contribute 44.83% to the total poisonous
      flora of the research area. Other important poisonous plants were Anagallis
      arvensis L., Cannabis sativa, Datura stramonium L., D. metel L., Euphorbia
      species, Heliotropium europaeum, Ipomoea tricolor, Jatropha curcas, Lolium
      temulentum L., Malus domestica, Mangifera indica L., Medicago sativa L.,
      Melilotus alba Desr., M. officinalis (L.) Lam., Mirabilis jalapa L., Narcissus
      tazetta, Nicotiana tabacum L., Sorghum halepense (L) Pers., and Xanthium
      strumarium. It was concluded that the local population had poor knowledge about
      the poisonous effect of the plants and the present research work was anticipated
      for use by health care professionals, veterinarians, farmers, homeowners, as well
      as botanically curious individuals.

PMID- 29348086
TI  - Pharmaceutical equivalent dissertation of Metformin hydrochloride brands.
AB  - The aim of study is to establish pharmaceutical equivalence of different brands
      of Metformin tablets available in Karachi, Pakistan. The quality control
      parameters which are studied are weight variation test, hardness test, thickness,
      friability, disintegration and dissolution specified by BP/USP (British and
      United State Pharmacopoeia). Weight variation and hardness value requirement was
      complied by all brands. Disintegration time for all brands was within range i.e.
      15 minutes and also complies with the BP/USP recommendation. All brands showed
      more than 90% drug release within forty five minutes. The present conclusion
      suggests that almost all the brands of Metformin that are available in Karachi
      meet the specification for quality control analysis. Assay performed by HPLC by
      keeping flow rate of 1.0 ml/min of the mobile phase and the quantitative
      evaluation at 225 nm was performed. The retention time of Metformin was found to
      be 2.5min. Method suitability for the quantitative determination of the drugs was
      proved by validation according to the International Conference on Harmonization
      (ICH) guidelines.

PMID- 29348087
TI  - Phytochemical screening and antibacterial activity of different solvent extracted
      samples of Arisaema jacquemontii.
AB  - The current research was carried out to assess the antibacterial activities and
      phytochemical analysis of the methanol, n-hexane, ethyl acetate, n-butanol
      soluble fractions and aqueous extracts of the tubers of Arisaema jacquemontii.
      All the extracts were tested for their antibacterial potential at 1, 2 and 3 mg
      disc-1 concentrations against 6 bacterial strains through disc diffusion
      suseptibility assay. The data suggested that different extracts showed varying
      degree of growth inhibition against the tested microbes. Statistical analysis
      revealed that n-hexane and ethyl acetate soluble fractions significantly
      inhibited the growth of all the bacterial strains at the tested concentrations.
      Moderate activities were recorded for n-butanol and methanolic extracted samples
      at different concentrations against all the tested strains of bacteria. P.
      aeruginosa, S. aureus and X. campestris showed resistance to all the tested
      concentrations of the aqueous extract. B. subtilis and K. pneumoniae were
      resistant at 1 and 2 mg disc-1 concentrations of the aqueous extract and 3 mg
      disc-1 of the same extract reduced the growth of the same bacteria. Phytochemical
      analysis of the different solvent extracted samples suggested the presence or
      absence of various metabolites including alkaloids, saponins, tannins, sterols,
      flavonoids, protein, carbohydrates and fats.

PMID- 29348088
TI  - Prevalence of Hepatitis C virus and its risk factors in blood donors in district
      Peshawar.
AB  - The current study was designed in order to elucidate the most sensitive method
      for daily practice as well as to evaluate the risk factors for HCV infection
      associated with blood transfusion in District Peshawar. A total of 1400 healthy
      volunteer blood donors were tested for Anti-HCV. A questionnaire was used to
      evaluate the risk factors. Initial testing of all blood samples was done by
      Immuno Chromatographic Technique (ICT) and confirmed by micro particle enzyme
      immunoassay (MEIA) and Enzyme Linked Immunosorbent Assay (ELISA). The comparison
      among ICT, ELISA and MEIA techniques was also evaluated for the purpose of
      sensitivity. Among 1400 blood donors, 26 (1.85%) cases were found positive for
      Anti-HCV. These 26 cases were positive on MEIA, 16 individuals were positive on
      ELISA while 14 were positive on ICT. These 26 cases had different histories of
      dental treatment (50%), traveled abroad (23.07%), surgery (11.53%), blood
      transfusion (7.69%) and unknown reason (7.69%). Among all these different
      histories of dental treatment and blood transfusion were the main risk factors
      for HCV infection. The results revealed that MEIA is a quick and reliable
      technique for routine screening of blood donors particularly for controlling the
      spread of HCV.

PMID- 29348089
TI  - A study of serological markers and lipid profile in non-alcoholic liver cirrhosis
      patients.
AB  - Cirrhosis is the end result of chronic liver damage, associated with altered
      serum biomarkers and lipid profile. However, only few studies regarding serum
      biomarkers and plasma lipid profile in non-alcoholic liver cirrhosis subjects
      have been undertaken in Pakistan. This study aimed to evaluate the degree of
      alterations of tumor markers and lipid profile in liver cirrhosis patients and in
      normal healthy individuals. Levels of serological markers and plasma lipid
      pattern was measured in liver cirrhosis patients and in sex and age matched
      normal healthy individuals (n=46). Tumor marker alpha-fetoprotein (AFP) was
      measured by ELISA, whereas plasma lipid profile and biomarker alanine aminotr
      ansferase (ALT) was determined by colorimetric assays. In patients with cirrhosis
      significant increase was observed in serum AFP and ALT levels when compared with
      healthy individuals (p<0.05).The triglyceride levels were found to be
      significantly higher, while LDL-C was significantly lower (p<0.05) in liver
      cirrhosis patients. There was no significant difference in the plasma
      concentration of cholesterol, total lipids and HDL-C in liver cirrhosis patients
      as compared with normal individuals. AFP and ALT are useful markers in the
      diagnosis of cirrhosis and can be used for the detection of hepatocellular
      carcinoma (HCC) in cirrhosis patients. The assessment of plasma lipids and
      lipoprotein pattern is also important for prognostic evaluation of patients with
      cirrhosis.

PMID- 29348090
TI  - Pharmacological validation of the folkloric uses of Cyperus rotundus L. in
      different ailments: An in vivo and in vitro research.
AB  - In vivo and in vitro research study was conducted on Cyperus rotundus to evaluate
      the sound mechanistic background in the treatment of gastrointestinal, bronchial
      and vascular disorders as well as in pain, emesis, pyrexia and bacterial
      infections. Results showed that crude extract of Cyperus rotundus (Cr.Cr)
      exhibited the dose-dependent spasmolytic effect in rabbit jejunum by inhibiting
      the spontaneous and K+ (80 mM)-induced contractions. Pretreatment of tissue with
      Cr. Cr caused the rightward shift of calcium concentration response curves,
      similar to verapamil. Cr. Cr also caused the relaxation of K+(80 mM)- and
      carbachol (1 uM)-induced contractions of trachea preparations, similar to that of
      verapamil. Moreover, Cr. Cr also relaxed the contraction induced by the K+ (80
      mM) and phenylephrine (1 uM) of aorta preparations. Data show that C. rotundus
      possess the spasmolytic, bronchodilator and vasodilator activities possibly
      through calcium channels blockade; validating its folkloric use in diarrhea,
      dyspepsia, bronchitis, asthma and hypertension in addition to antibacterial,
      antiemetic, antipyretic and analgesic activities.

PMID- 29348091
TI  - Synthesis and antibacterial activity of the sulfonamide based schiff base and its
      transition metal (II) complexes.
AB  - A Schiff base 3 has been synthesized by equimolar reaction (condensation) of
      sulfonamide i.e. sulfamethoxypyridazine 1 and substituted aromatic aldehyde i.e.
      2-Hydroxy-1-Napthalene aldehyde 2. The synthesized Schiff base 3 and its Metal
      (II) complexes were characterized by its physical, analytical (CHN analysis) and
      spectral (UV & IR) analysis. The Staphylococcus aureus and Escherichia coli
      bacterial strains were used for antibacterial activity of Sulfamethoxypyridazine
      1, its Schiff base 3 and its transition metal (II) complexes 4-8. All of them
      showed varied levels of activity.

PMID- 29348092
TI  - Prescribing pattern of angiotensin receptor blocker: A study of errors and drug
      drug interactions.
AB  - Prescriptions comprising multi-drug therapy mostly illustrate the prescribing
      error. The phenomenon of error is bonded with human inaccuracy. The erroneous
      practice is observed in under developed countries like Pakistan, Bangladesh and
      also in developed ones. Consequently drug-drug interaction is one of the most
      common error associated with potentially serious adverse response even death.
      Accordingly the present study was conducted to assess the prevalence of
      prescribing errors and drug-drug interactions in out-patients receiving
      angiotensin receptor blockers. The study was done with population size one
      hundred fifty prescriptions obtained from different out-patient settings in
      Karachi. The prescriptions were screened for prescribing errors and risk factors
      for drug-drug interactions. Drug-drug interactions were recognized by
      Micromedex.2.0.Drug-Reax(r)database. The most common type of error was omission
      error. These errors were patient's age, weight and diagnosis found in 51.3%,
      97.3% and 74% of prescriptions, respectively. The prevalence of drug-drug
      interaction was 38%. A total of 746 drugs were prescribed with an average of 5
      drugs per prescription and 450 medication errors were detected. Majority of the
      interaction were moderate (19.33%), others were minor (14%) and major (6%) in
      severity. Patients who prescribed many drugs (more than 5 drugs in a while) had a
      higher risk of developing drug-drug interactions (OR=4.76; 95% CI=2.30-9.64;
      p=0.0001*).The study data reports the occurrence of prescribing errors in Karachi
      and also necessitate the need of clinical pharmacist's services in health care
      system. The step will help to minimize the risk factors by having the drug
      prescriptions reviewed by the pharmacists.

PMID- 29348093
TI  - Antifungal and cytotoxic activities of selected medicinal plants from Malaysia.
AB  - This study was conducted to investigate the antifungal potential and cytotoxicity
      of selected medicinal plants from Malaysia. The extracts from the stem of Cissus
      quadrangularis and the leaves of Asplenium nidus, Pereskia bleo, Persicaria
      odorata and Sauropus androgynus were assayed against six fungi using p
      iodonitrotetrazolium-based on colorimetric broth microdilution method. All the
      plant extracts were found to be fungicidal against at least one type of fungus.
      The strongest fungicidal activity (minimum fungicidal concentration=0.16 mg/mL)
      were exhibited by the hexane extract of C. quadrangularis, the hexane,
      chloroform, ethanol and methanol extracts of P. bleo, the hexane and ethyl
      acetate extracts of P. odorata, and the water extract of A. nidus. In terms of
      cytotoxicity on the African monkey kidney epithelial (Vero) cells, the chloroform
      extract of P. odorata produced the lowest 50% cytotoxic concentration (100.3 +/-
      4.2 MU g/mL). In contrast, none of the water extracts from the studied plants
      caused significant toxicity on the cells. The water extract of A. nidus warrants
      further investigation since it showed the strongest fungicidal activity and the
      highest total activity (179.22 L/g) against Issatchenkia orientalis, and did not
      cause any toxicity to the Vero cells.

PMID- 29348094
TI  - In vitro Salmonella typhi biofilm formation on gallstones and its disruption by
      Manuka honey.
AB  - Biofilm is a complex community of single or different types of microorganisms
      (bacteria, viruses, fungi, protozoa) attached to a surface and stick to each
      other through production of extracellular matrix. Salmonella typhi forms biofilm
      on cholesterol gallstones resulting in carrier state. Once formed, biofilm is
      difficult to treat. To date cholecystectomy is the only cure for this condition.
      Manuka honey is known to have tremendous antibiofilm activity against various
      organisms. S. typhi biofilm was grown in vitro on clinical samples of human
      cholesterol gallstones by Gallstone tube assay method for 12 days. Biofilm mass
      was quantified on day 1, 5, 7, 9 and 12 by crystal violet assay and was also
      examined by scanning electron microscope. Three concentrations w/v of Manuka
      honey (40%, 60% and 80%) were used, each one at 24, 48 and 72 hours. The most
      effective concentration (80% w/v) was repeated on two sets of gallstones. Biofilm
      mass was re quantified by crystal violet assay and was examined by scanning
      electron microscope. S. typhi formed uniform biofilm on cholesterol gallstone
      surface. The optical density measurements exhibited a rising pattern with time
      thereby indicating an increase in biofilm mass. It was 0.2 on day 1 and 0.9 on
      day 12. With 80% w/v Manuka honey, biofilm mass decreased most effectively with
      0.5 OD after 72 hours. Biofilm formation by S, typhi on gallstones is surface
      specific and bile dependant. Either increasing the duration (beyond 72 hours) of
      the effective concentration (80% w/v) of honey or increasing the concentration
      (above 80%) of honey for a specific duration (72 hour) may cause complete
      disruption of the S. typhi biofilm on gallstone. S. typhi forms biofilm on
      cholesterol gallstones surface in vitro and it can be visualized by scanning
      electron microscopy. Biofilm mass can be quantified using crystal violet assay.
      Among various concentrations 80% Manuka honey for 72 hours is most effective in
      disrupting S. typhi biofilm on gallstones in vitro as evident from crystal violet
      assay.

PMID- 29348095
TI  - Estimation of simvastatin and cetirizine by RP-LC method: Application to freeze
      and thaw (FT) stability studies.
AB  - Sensitive, simple, reliable and rapid HPLC technique for the estimation of
      simvastatin (SMV) and cetirizine has been designed in this study. The
      chromatographic conditions were set using Shimadzu LC-10 AT VP pump, with UV
      detector (SPD-10 AV-VP). System integration was performed with CBM-102 (Bus
      Module). Partitioning of components was attained with pre-packed C-18 column of
      Purospher Star (5 MUm, 250 x 4.6 mm) at ambient conditions. Injected volume of
      sample was 10 MUl. Mobile phase was composed of 50:50 v/v ratio of
      Acetonitrile/water (pH 3.0 adjusted with ortho-phosphoric acid) having 2
      ml/minutes rate of flow. Compounds were detected in UV region at 225 nm. Percent
      Recovery of simvastatin was observed in the range of 98-102%. All results were
      found in accept table range of specification. The projected method is consistent,
      specific, precise, and rapid, that can be employed to quantitate the SMV along
      with cetirizine HCl. It was estimated by 3 successive cycles of freeze and thaw
      stability. Results of FT samples were found within accept table limits the method
      was developed and validated in raw materials, bulk formulations and final drug
      products.

PMID- 29348096
TI  - Antiulcer activity of methanol-chloroform extract of Channa striatus fillet.
AB  - Channa striatus (Haruan) is Malaysian freshwater fish that is traditionally used
      to treat ailments related to wound and also ulcers. The aimed of the present
      study was to determine the mechanisms of anti-ulcer activity of chloroform:
      methanol extract of C. striatus fillet (CMCS) in rats. The antiulcer profile of
      CMCS, given orally in the doses of 50, 250 and 500mg/kg, was assessed using the
      ethanol- and indomethacin-induced gastric ulcer models. The mechanisms of
      antiulcer of CMCS were determined as follows; i) the antisecretory activity of
      CMCS was measured using the pyloric ligation rat model, and; ii) the role of
      nitric oxide (NO) and sulfhydryl compounds in the modulation of CMCS antiulcer
      activity were determined by pre-treating the rats with L-NAME or NEM,
      respectively, followed by the pre-treatment of rats with CMCS before subjecting
      the animals to the ethanol-induced gastric ulcer model. From the results
      obtained, CMCS exerted significant (P<0.05) antiulcer activity in both models of
      gastric ulcer wherein the macroscopic and microscopic analysis of the stomach
      supported the antiulcer claim. With regard to its antisecretory effect, CMCS did
      not change the volume and pH, but reduce the total acidity only at the lower
      doses of the gastric juice. Moreover, CMCS demonstrated antiulcer activity was
      reversed by NEM, but not affected by L-NAME. In conclusion, CMCS shows antiulcer
      activity that is modulated via its cytoprotective, but not antisecretory effect,
      and in the presence of sulfhysryl compounds, but not NO.

PMID- 29348097
TI  - A novel spectrophotometric determination of caroverine in pharmaceutical
      formulations via derivatization with Folin-ciocalteu Phenol reagent.
AB  - In this study we have reported a new, fast and extraction free spectrophotometric
      procedure for the assessment of caroverine in pharmaceutical raw and tablet
      dosage forms. In the reported visible spectrophotometric procedure tungstate in
      Folin-Ciocalteu phenol reagent is reduced in alkaline medium and produces the
      blue colored chromogen that shows Lambdamax at 740nm with the calibration range
      of 2-28MUg/ml. The LOD and LOQ values are 1.15 and 3.81MUg/ml respectively. The
      newly developed analytical procedure is used to determine caroverine in raw
      material of and commercial tablets dosage forms. The spectrophotometric method
      represented in this study is simple, rapid and extraction free. It may easily be
      utilized for the determination of caroverine in pharmaceutical laboratories for
      quality control and stability studies purpose.

PMID- 29348098
TI  - Safety of fenbendazole in common peafowl (Pavo cristatus).
AB  - The present study was undertaken to find out the safety levels of fenbendazole in
      common peafowl. This bird, raised on aviaries and zoos, can be severely
      parasitized with Ascaridia galli (enteric worms) and Syngamus trachea (gapeworm)
      along with other parasitic worms. Fenbendazole is a highly effective
      benzimidazole-class anthelmintic in animals. The objective of this work was to
      provide target animal safety data in young peafowl and to demonstrate
      reproductive safety in adult birds. During the experimental study, diets
      containing fenbendazole at 0, 100, 200 and 300 ppm were fed for 21 days (three
      times the normal treatment duration). Data for feed consumption, feed conversion
      rate, and body weights were recorded for each bird in each group. Drug
      concentrations in different tissues of birds were determined to correlate
      concentrations with clinical observations, clinical pathology, and histologic
      findings. There were no morbidities or mortalities after study day 21.
      Additionally, there were no statistically significant treatment-related
      differences among above mentioned parameters. Analysis of fenbendazole
      concentrations in kidney, liver, leg/thigh, and breast muscle and skin with
      associated fat revealed that, even at the highest dose level used and with no
      feed withdrawal, fenbendazole concentrations were relatively low in these
      tissues. These findings indicate that fenbendazole has a relatively wide margin
      of safety in young peafowl and that the proposed dose of 100 ppm in the feed for
      7 consecutive days is well within the margin of safety. In the reproductive
      safety study, five breeder peafowl farms fed fendbendazole at 100ppm for 7 days
      and collected data on hatching percentage of peahen eggs before and after
      treatment. Reproductive performance in peahen was not adversely affected.

PMID- 29348099
TI  - Spray-dried curcumin nanoemulsion: A new road to improvement of oral
      bioavailability of curcumin.
AB  - In this study a new soluble solid curcumin nanoemulsion powder was prepared using
      spray-drying technology to improve the solubility and bioavailability of
      curcumin. The liquid nanoemulsion consisted of curcumin, Capryol 90, Transcutol
      P, and Cremophor RH40. The solid nanoemulsion was prepared by spray-drying the
      liquid nanoemulsion in laboratory spray dryer, using lactose as solid carrier.
      The in vitro release from powder formulation was 97.6% within 15 min while the
      release from the curcumin crystalline was about 10%. An oral pharmacokinetic
      study was conducted in rats and the relative bioavailability of spray-dried
      curcumin powder significantly increased compared with that of curcumin
      crystalline. The Cmax value of solid curcumin nanoemulsion powder was 5.5-fold
      greater than the value of the curcumin crystalline in aqueous suspension. The
      absorption mechanism of the spray-dried curcumin powders was discussed. The
      results indicate that spray-drying in combination with nanoemulsion was a
      powerful methodology for improving the dissolution rate and oral bioavailability
      of curcumin.

PMID- 29348100
TI  - Rapid diagnostic method of tobacco products in saliva by fourier transform
      infrared spectroscopy (FTIR).
AB  - The present study was designed to explore the easy and fast method diagnosis of
      tobacco products in saliva of tobacco users (TU) by FTIR. Sixty four male tobacco
      users (TU) with mean age range 15.3 to 30.7 years were randomly selected for
      collection of saliva samples before and after tobacco use (smoking, chewing and
      dipping tobacco). Twenty were the smoking tobacco users (STU), 24 were chewing
      tobacco users (CTU) and 20 were dipping tobacco users (DTU). CTU were the users
      of Mainpuri (n=10) and users of PEN, FIT, 2100 (n=14). Forty eight saliva samples
      of age and gender matched healthy individuals with negative personal or family
      history of any addiction were also collected for comparison which served as
      controls. All were analyzed for their salivary flow rate, salivary pH and
      salivary diagnostic bands by FTIR. Significantly increased SFR (p<0.05) and
      salivary pH were found in after chewing tobacco as compared to before its
      chewing. The comparison between after tobacco use and controls we found decreased
      SFR and salivary pH for STU. Significant decreased SFR and increased salivary pH
      were found before or after use of dipping tobacco as compared to controls. Sharp
      bands at 735-745 cm-1 were found and may be used as salivary diagnostic bands for
      STU, 945-949 cm-1 for DTU and 900-915 cm-1 for CTU as well as DTU. In conclusion,
      the salivary diagnostic bands were found at 735-745 cm-1, 900-915 cm-1 and 945
      949 cm-1 for TU by easy and fast method using FTIR.

PMID- 29348101
TI  - Effects of gamma irradiation on the physico-chemical and biological properties of
      levofloxacin.
AB  - The aim of the present study was to examine the effect of gamma radiation on
      levofloxacin. Powder form of levofloxacin was subjected to different radiation
      doses (25, 50, 75, 100 and 125kGy) of Cobalt-60 source in a Gammacell-220 at a
      rate of 8.5 Gray/hr. The effect of radiation has been investigated with the aid
      of different spectroscopic techniques (UV-Vis, FT-IR), scanning electron
      microscopy (SEM), X-ray diffraction (XRD), and by antibacterial activities. UV
      data did not reveal significant changes in the structure of levofloxacin which is
      supported by scanning electron microscopy. However, X-rays diffraction shows a
      change in crystallinity of levofloxacin to an amorphous structure and this has
      been reflected on the morphology of this compound as indicated by SEM images. The
      antibacterial activities, on the other hand, reveal resistance of irradiated
      levofloxacin against bacteria, where some bacteria were highly affected by the
      irradiated drug. Similarly, FT-IR data show some changes in the functional groups
      principal absorption bands, in the IR spectrum, at frequencies 3286, 2846, 1716
      and 1620 cm-1 for the O-H stretching band of quinolone, C-H stretching band, and
      C=O stretching band of carboxylic and pyridine. In addition, new peaks appeared
      which were not seen in the non-irradiated spectrum. In conclusion, some changes
      occurred in levofloxacin drug with the passage of radiation but the drug was
      chemically stable.

PMID- 29348102
TI  - Phytochemical screening and antibacterial activity of Cyclamen persicum Mill
      tuber extracts.
AB  - The emerging drug resistance bacteria increased the demand on the discovery of
      antibiotics from natural sources. This research was aimed to study the
      antibacterial reactivity; as well as the phytochemicals, of the wild type of
      Cyclamen persicum, using nine different extraction methods where four solvents
      (Methanol, Ethanol, Hexane; and Water) were involved with varied extraction
      periods ranged from 2 up to 10 hours. The antibacterial activity of crude
      methanol extract (CME) was found as the best method of extraction, with
      particular emphasis on the method with prolonged extraction time of (10 hrs). The
      antibacterial activities of produced CME were determined by using agar diffusion
      method against two of gram-positive bacteria and two gram-negative ones. The CME
      treated Mueller-Hinton-Agar plates, were exhibited antibacterial effects against
      the gram-positive bacteria (Staphylococcus aureus and Bacillus subtilis) by
      showing of inhibition zone after overnight incubation, while nothing was noticed
      on those of gram negative ones (Pseudomonas aeruginosa and Escherichia coli).
      These results that proved the antibacterial activity of the Cyclamen persicum
      tubers were positively tested the Saponin glycosides from plant. In addition to
      that, methanol solvent could be the useful method for extractions of Cyclamen and
      can be used in any developing drugs against pathogenic gram positive bacteria.

PMID- 29348103
TI  - Prevalence of non alcoholic fatty liver and Non alcoholic Steatohepatitis in
      Peshawar Cantonment, Khyber Pakhtunkhwa, Pakistan.
AB  - Non-alcoholic fatty liver disease prevalence has not been well established. The
      aims of this study was to define prospectively non-alcoholic steatohepatitis
      (NASH) and non-alcoholic fatty liver disease (NAFLD) prevalence in hospitalized
      and ambulatory patients 20-65 years old during June 2013 to June 2014 were
      selected from Combined Military Hospital Peshawar Cantonment area. A base line
      questionnaire and right upper quadrant ultrasound was completed by all patients.
      On identifications of fatty liver among the selected cases further lab test data
      and liver biopsy reports were obtained. Mean BMI of female was 29.9 + 5.65 while
      prevalence of hypertension and diabetes was 49.8% and 16.6% respectively. Among
      all patients 62% were Punjabies, 23% were Pathans while 12% were Sindhies.
      Overall NAFLD prevalence was 47% while NASH was confirmed in 20 patients (12.3%
      of total and 30%of ultrasound positive patients). Pathans had the highest
      prevalence of NAFLD (58.5%) as compared to Punjabies (44.5%) and Sindhies
      (35.3%). Pathans also had a higher prevalence of NASH compared with Punjabies
      (19.5% VS 10%: P= 0.03). In general, NAFLD patients were more prevalent among
      male (59%), Diabetic (P<0.00005), hypertensive (P<0.00005) and older (P =0.005).
      They consumed more fast food (P=.049) had a higher BMI (P<0.0005) and had little
      or no exercise as compared to their normal or non NAFLD counter parts (P=0.02).
      NAFLD was found in 75% and NASH in 22.5% among the 26 diabetic patients. ALT,
      AST, BMI, insulin, quantitative insulin sensitivity checks index and cytokeratin 
      18 correlated with NASH. It was concluded that NAFLD and NASH prevalence is
      higher than estimated previously, Pathans and Patients with diabetes are at high
      risk.

PMID- 29348104
TI  - Disposition kinetics of omeprazole in healthy female volunteers in Faisalabad.
AB  - Omeprazole (OMP) a proton pump inhibitor is widely used to suppress gastric acid
      secretions of parietal cells of stomach and metabolized predominantly by CYP2C19.
      The objective of the present study was to investigate the pharmacokinetics and
      dosage regimen of OMP, after its single oral administration in eight healthy
      adult female subjects. Blood samples were collected at different time intervals
      after oral administration and their pH was measured. Plasma concentration of OMP
      was determined by high performance liquid chromatography (HPLC) system equipped
      with UV-visible Detector. The concentration versus time data was used to compute
      the pharmacokinetic parameters with the help of computer software programme
      MW/PHRAM APO version 3.02.Peak plasma concentration was (Cmax) 0.38+/-0.04 MUg/ml
      achieved at 2.07+/-0.22 hrs. The elimination half-life (t1/2 beta) was1.82 +/-
      0.42 hrs. Volume of distribution (Vd) in the present study was 0.40 +/- 0.07 l/kg
      with total body clearance (ClB) 0.19 +/- 0.02 l/hr/kg and area under the curve
      (AUC) 1.89 +/- 0.23 MUg.hr/ml.The pharmacokinetic properties which are different
      from the literature after oral administration of 20 mg OMP in eight healthy
      female volunteers may be due to the variations of environment and genetic
      variation between Pakistan and drug manufacturing of foreign countries.

PMID- 29348105
TI  - Report: Preparation of levodopa/carbidopa compound drug resins.
AB  - The main objective of this study was to prepare the levodopa/carbidopa compound
      drug resins and investigate affecting factors such as drug concentration,
      temperature, particle size. The drug resins were made by bath method and the
      effects of above factors during the process of preparation was studied. Studies
      on the stabilities of drugs and drug resins were carried out by HPLC. The Results
      showed that the preparation of drug resins was influenced by drug concentration,
      resin particle size, reaction temperature and solvent concentration. In certain
      conditions the degradation peaks were found in the chromatograms of levodopa and
      carbidopa while the drug-resins remained undegraded. The study indicates that the
      drug resin technology is an effective way of improving stability of the drug and
      possesses certain sustained-release effects.

PMID- 29348106
TI  - Report: Palladium glutathione, N-acetylcysteine, D-penicillamine conjugation
      chemistry.
AB  - The metalloelement Palladium has a number of potential Pharmaco-clinical
      advantages. Palladium compounds have antiviral, antibacterial, neuroprotective
      and antitumor properties. However studies have also indicated some mild to
      serious toxic effects of Palladium metalloelements. Biothiols are important
      antioxidants that provide protection against metals toxicity. The interaction of
      metalloelements with biothiols can provide valuable information about the level
      of toxicity of the metalloelements and about the protective role of biothiols
      thereof. In this piece of work the effect of salt and complexes of Palladium on
      the status of different thiols (GSH, NAC, and D-Pen) in aqueous medium, were
      examined, The thiol quantification was carried out using Elman's method through
      UV-visible spectrophotometry and 1H- NMR. Results of the study performed in
      aqueous medium showed that level of different thiols depleted after the addition
      of the inorganic salts and organic complexes of Palladium. The mechanism of
      interaction of Palladium with thiols was examined using H-NMR. The results
      indicate that the depletion in the level of thiols may be due to 1:1 or 1:2
      conjugation of Palladium with thiols. These conjugation reactions further suggest
      that the Palladium have xenobiotic nature causing oxidative stress and thiols
      play their role in detoxification and biotransformation of these metalloelements.

PMID- 29348107
TI  - Report: Regional variation in the chemical composition and antioxidant activity
      of Rosmarinus officinalis L. from China and the Mediterranean region.
AB  - Rosemary is an aromatic evergreen shrubby herb that is native to the
      Mediterranean region. This herb is now widely cultivated in many regions of the
      world. Rosemary is widely used in traditional Chinese medicines, foods,
      nutraceuticals and cosmetics. Hydro distilled essential oils, obtained from
      rosemary in China and the Mediterranean region, were analysed by gas
      chromatography-mass spectrometry (GC-MS). Thirty-seven compounds accounting for
      94.97%-99.72% of the oils were identified. The majority of the compounds in the
      essential oils exhibited no significant differences (table 1 and fig. 1). The
      extracts were prepared with three solvents of different polarity
      (dichloromethane, ethyl acetate and aqueous). The ethyl acetate fractions
      exhibited the highest phenol content and were found to be significantly more
      active than the dichloromethane and aqueous fractions (fig. 2). Antioxidant
      activity (by DPPH radical scavenging, ferric ion reduction (FRAP) and
      thiobarbituric acid reactive substance (TBARS)) was also assessed. The ethyl
      acetate extracts of Yunnan had the highest amount of antioxidant capacity from
      China by DPPH and TBARS, with the lowest IC50 values being 0.0011 mg/ml, and
      1.6611 mg/ml, respectively. In conclusion, the antioxidant activities of the
      essential oils and ethyl acetate extracts from rosemary obtained by three
      different testing methods revealed higher antioxidant activity from rosemary
      grown in China than in the Mediterranean region. These results suggested that
      Chinese rosemary should be widely used in food, traditional medicine, cosmetics
      and perfume products, as well as other chemical industries.

PMID- 29348108
TI  - Report: Fast chromatographic screening method for 7 drugs of potential threat in
      drug facilitated crimes.
AB  - In cases where pharmaceuticals and pharmaceutical candidates are involved in drug
      facilitated crimes (DFC), like organ theft, robbery, rape and suicides, the
      analysis of drug powders or solution residues found in crime scenes may give idea
      on what the victims have ingested. An easy and fast simultaneous determination of
      7 drugs; GHB (gamma-hydroxybutyrate), GBL (gamma-butyrolactone), norketamine,
      ketamine, fenobarbital, fenitoin and thiopental which have the potential to be
      used in DFC was performed. The method required no sample preparation and has 12
      minutes elution time with a good chromatographic separation. The separation was
      carried out on a C18 monolithic column with UV detection at 215 and 237nm. All r2
      values were >=0.99 and the linear ranges were between 0.9956-1.0000. The LOD and
      LOQ values were between 0.56-5.55MUgmL-1 and 1.69-16.82MUgmL-1 respectively. The
      repeatability values were <7.35%. This is the first study in the simultaneous
      screening of the above mentioned drugs using HPLC.

PMID- 29348109
TI  - Review: Beyond conventional therapies: Complementary and alternative medicine in
      the management of hypertension: An evidence-based review.
AB  - Hypertension is one of the major causes of morbidity and mortality. Worldwide,
      Hypertension is estimated to cause 7.5 million deaths, about 12.8% of the total
      of all deaths. This accounts for 57 million disability adjusted life years
      (DALYS) or 3.7% of total DALYS. This led WHO to set a target of 25% reduction in
      prevalence by 2025. To reach that, WHO has adopted non-conventional methods for
      the management of hypertension? Despite worldwide popularity of such non
      conventional therapies, only small volume of evidence exists that supports its
      effectiveness. This review attempted to make a critical appraisal of the
      evidence, with the aim to (1) describe the therapeutic modalities frequently
      used, and (2) review the current level of evidence attributable to each modality.
      Databases from Cochrane Library, MEDLINE, PUBMED, and EMBASE were searched from
      2005-2015. A total of 23 publications have been identified and selected. Out of
      these, 15 systematic reviews and/or meta-analysis of RCTs, 5 RCTs, 1 non-RCT, and
      2 observational studies without control. Among those 23 publications, therapeutic
      modalities identified are: fish oil, qigong, yoga, coenzyme Q10, melatonin,
      meditation, vitamin D, vitamin C, monounsaturated fatty acids, dietary amino
      acids, chiropractic, osteopathy, folate, inorganic nitrate, beetroot juice,
      beetroot bread, magnesium, and L-arginine. The followings were found to have weak
      or no evidence: fish oil, yoga, vitamin D, monounsaturated fatty acid, dietary
      amino-acids, and osteopathy. Those found to have significant reduction in blood
      pressure are: magnesium, qigong, melatonin, meditation, vitamin C, chiropractic,
      folate, inorganic nitrate, beetroot juice and L-arginine. Coenzyme Q10on the
      other hand, showed contradicting results were some studies found weak or no
      effect on blood pressure while others showed significant blood pressure reduction
      effect. By virtue of the research designs and methodologies, the evidence
      contributed from these studies is at level 1. Results from this review suggest
      that certain non-conventional therapies may be effective in treating hypertension
      and improving cardiac function and therefore considered as part of an evidence
      based approach.

PMID- 29348110
TI  - The Role of Ethnicity and Environment in the Regulation of Response to Sensory
      Stimulus in Children: Protocol and Pilot Findings of a Neurophysiological Study.
AB  - BACKGROUND: The ability to regulate the response to sensory stimuli has been
      associated with successful behavioral patterns necessary for daily activities.
      However, it is not known whether a child's ethnicity and environment can
      influence autonomic regulatory mechanisms. OBJECTIVE: This study aims to explore
      the role of ethnicity and environment in the regulation of responses to sensory
      stimuli in children. METHODS: In this study, we intend to recruit 128 children
      from different ethnic groups or environment contexts as follows: (1) 32 typically
      developing Chinese children living in Hong Kong; (2) 32 typically developing
      Filipino children living in Hong Kong; (3) 32 typically developing Filipino
      children who are living in urban areas; and (4) 32 typically developing Filipino
      children who are living in rural areas in Philippines. Autonomic activity (heart
      rate variability [HRV] and electrodermal activity [EDA]) will be measured and
      recorded using Polar H2 heart rate monitor and eSense GSR skin response sensor.
      Autonomic activity (HRV-low frequency, HRV-high frequency, and EDA) at different
      conditions between pairwise groupings will be tested using multivariate analysis
      of variance (MANOVA). All significant levels will be set at P <=.05. RESULTS: We
      present the research protocol of this study, as well as a short discussion of the
      preliminary findings from our pilot data, with consequent power and sample size
      analysis that informs the appropriate sample needed to test our hypothesis.
      CONCLUSIONS: This study will increase the understanding on the role of individual
      differences related to a child's ethnicity and environment in the regulation of
      response to sensory stimuli. The findings of this research may further shed light
      on the evaluation and treatment planning for children across and within cultures.

PMID- 29348111
TI  - Leveraging Social Networking Sites for an Autoimmune Hepatitis Genetic
      Repository: Pilot Study to Evaluate Feasibility.
AB  - BACKGROUND: Conventional approaches to participant recruitment are often
      inadequate in rare disease investigation. Social networking sites such as
      Facebook may provide a vehicle to circumvent common research limitations and
      pitfalls. We report our preliminary experience with Facebook-based methodology
      for participant recruitment and participation into an ongoing study of autoimmune
      hepatitis (AIH). OBJECTIVE: The goal of our research was to conduct a pilot study
      to assess whether a Facebook-based methodology is capable of recruiting
      geographically widespread participants into AIH patient-oriented research and
      obtaining quality phenotypic data. METHODS: We established a Facebook community,
      the Autoimmune Hepatitis Research Network (AHRN), in 2014 to provide a secure and
      reputable distillation of current literature and AIH research opportunities.
      Quarterly advertisements for our ongoing observational AIH study were posted on
      the AHRN over 2 years. Interested and self-reported AIH participants were
      subsequently enrolled after review of study materials and completion of an
      informed consent by our study coordinator. Participants returned completed study
      materials, including epidemiologic questionnaires and genetic material, to our
      facility via mail. Outside medical records were obtained and reviewed by a study
      physician. RESULTS: We successfully obtained all study materials from 29
      participants with self-reported AIH within 2 years from 20 different states.
      Liver biopsy results were available for 90% (26/29) of participants, of which 81%
      (21/29) had findings consistent with AIH, 15% (4/29) were suggestive of AIH with
      features of primary biliary cholangitis (PBC), and 4% (1/29) had PBC alone. A
      total of 83% (24/29) had at least 2 of 3 proposed criteria: positive autoimmune
      markers, consistent histologic findings of AIH on liver biopsy, and reported
      treatment with immunosuppressant medications. Self-reported and physician records
      were discrepant for immunosuppressant medications or for AIH/PBC diagnoses in 4
      patients. CONCLUSIONS: Facebook can be an effective ancillary tool for
      facilitating patient-oriented research in rare diseases. A social media-based
      approach transcends established limitations in rare disease research and can
      further develop research communities.

PMID- 29348112
TI  - Comparing Short Dental Implants to Standard Dental Implants: Protocol for a
      Systematic Review.
AB  - BACKGROUND: Short dental implants have been proposed as a simpler, cheaper, and
      faster alternative for the rehabilitation of atrophic edentulous areas to avoid
      the disadvantages of surgical techniques for increasing bone volume. OBJECTIVE:
      This review will compare short implants (4 to 8 mm) to standard implants (larger
      than 8 mm) in edentulous jaws, evaluating on the basis of marginal bone loss
      (MBL), survival rate, complications, and prosthesis failure. METHODS: We will
      electronically search for randomized controlled trials comparing short dental
      implants to standard dental implants in the following databases: PubMed, Web of
      Science, EMBASE, Scopus, the Cochrane Central Register of Controlled Trials, and
      ClinicalTrials.gov with English language restrictions. We will manually search
      the reference lists of relevant reviews and the included articles in this review.
      The following journals will also be searched: European Journal of Oral
      Implantology, Clinical Oral Implants Research, and Clinical Implant Dentistry and
      Related Research. Two reviewers will independently perform the study selection,
      data extraction and quality assessment (using the Cochrane Collaboration tool) of
      included studies. All meta-analysis procedures including appropriate effect size
      combination, sub-group analysis, meta-regression, assessing publication or
      reporting bias will be performed using Stata (Statacorp, TEXAS) version 12.1.
      RESULTS: Short implant effectiveness will be assessed using the mean difference
      of MBL in terms of weighted mean difference (WMD) and standardized mean
      difference (SMD) using Cohen's method. The combined effect size measures in
      addition to the related 95% confidence intervals will be estimated by a fixed
      effect model. The heterogeneity of the related effect size will be assessed using
      a Q Cochrane test and I2 measure. The MBL will be presented by a standardized
      mean difference with a 95% confidence interval. The survival rate of implants,
      prostheses failures, and complications will be reported using a risk ratio at 95%
      confidence interval (P<.05). CONCLUSIONS: The present protocol illustrates an
      appropriate method to perform the systematic review and ensures transparency for
      the completed review. The results will be published in a peer-reviewed journal
      and social networks. In addition, an ethics approval is not considered necessary.
      TRIAL REGISTRATION: PROSPERO registration number: CRD42016048363;
      https://www.crd.york.ac.uk/PROSPERO/ display_record.asp?ID=CRD42016048363
      (Archived by WebCite at http://www.webcitation.org/6wZ7Fntry).

PMID- 29348113
TI  - GENETICS IN ENDOCRINOLOGY: The expanding genetic horizon of primary
      aldosteronism.
AB  - Aldosterone is the main mineralocorticoid hormone in humans and plays a key role
      in maintaining water and electrolyte homeostasis. Primary aldosteronism (PA),
      characterized by autonomous aldosterone overproduction by the adrenal glands,
      affects 6% of the general hypertensive population and can be either sporadic or
      familial. Aldosterone-producing adenoma (APA) and bilateral adrenal hyperplasia
      (BAH) are the two most frequent subtypes of sporadic PA and 4 forms of familial
      hyperaldosteronism (FH-I to FH-IV) have been identified. Over the last six years,
      the introduction of next-generation sequencing has significantly improved our
      understanding of the molecular mechanisms responsible for autonomous aldosterone
      overproduction in both sporadic and familial PA. Somatic mutations in four genes
      (KCNJ5, ATP1A1, ATP2B3 and CACNA1D), differently implicated in intracellular ion
      homeostasis, have been identified in nearly 60% of the sporadic APAs. Germline
      mutations in KCNJ5 and CACNA1H cause FH-III and FH-IV, respectively, while
      germline mutations in CACNA1D cause the rare PASNA syndrome, featuring primary
      aldosteronism seizures and neurological abnormalities. Further studies are
      warranted to identify the molecular mechanisms underlying BAH and FH-II, the most
      common forms of sporadic and familial PA whose molecular basis is yet to be
      uncovered.

PMID- 29348114
TI  - Question 2: Is it safe to use the centre of the heel for obtaining capillary
      blood samples in neonates?

PMID- 29348115
TI  - Investigation of developmental delay.

PMID- 29348116
TI  - Intensive care: because we can or because we should?

PMID- 29348117
TI  - Graves' disease. Time to move on.

PMID- 29348118
TI  - Targeted Deletion of Adipocyte Abca1 (ATP-Binding Cassette Transporter A1)
      Impairs Diet-Induced Obesity.
AB  - OBJECTIVE: Adipose tissue cholesterol increases with adipocyte triglyceride
      content and size during development of obesity. However, how adipocyte
      cholesterol affects adipocyte function is poorly understood. The aim of this
      study was to evaluate the role of the cellular cholesterol exporter, Abca1 (ATP
      binding cassette transporter A1), on adipose tissue function during diet-induced
      obesity. APPROACH AND RESULTS: Adiponectin Cre recombinase transgenic mice were
      crossed with Abca1flox/flox mice to generate ASKO (adipocyte-specific Abca1
      knockout) mice. Control and ASKO mice were then fed a high-fat, high-cholesterol
      (45% calories as fat and 0.2% cholesterol) diet for 16 weeks. Compared with
      control mice, ASKO mice had a 2-fold increase in adipocyte plasma membrane
      cholesterol content and significantly lower body weight, epididymal fat pad
      weight, and adipocyte size. ASKO versus control adipose tissue had decreased
      PPARgamma (peroxisome proliferator-activated receptor gamma) and CCAAT/enhancer
      binding protein expression, nuclear SREBP1 (sterol regulatory element-binding
      protein 1) protein, lipogenesis, and triglyceride accretion but similar Akt
      activation after acute insulin stimulation. Acute siRNA-mediated Abca1 silencing
      during 3T3L1 adipocyte differentiation reduced adipocyte Abca1 and PPARgamma
      protein expression and triglyceride content. Systemic stimulated triglyceride
      lipolysis and glucose homeostasis were similar between control and ASKO mice.
      CONCLUSIONS: Adipocyte Abca1 is a key regulator of adipocyte lipogenesis and
      lipid accretion, likely because of increased adipose tissue membrane cholesterol,
      resulting in decreased activation of lipogenic transcription factors PPARgamma
      and SREBP1.

PMID- 29348120
TI  - APOC3 Loss-of-Function Mutations, Remnant Cholesterol, Low-Density Lipoprotein
      Cholesterol, and Cardiovascular Risk: Mediation- and Meta-Analyses of 137 895
      Individuals.
AB  - OBJECTIVE: Loss-of-function mutations in APOC3 associate with low remnant
      cholesterol levels and low risk of ischemic vascular disease (IVD). Because some
      studies show an additional association with low levels of low-density lipoprotein
      cholesterol (LDL-C), low LDL-C may explain the low risk of IVD in APOC3 loss-of
      function heterozygotes. We tested to what extent the low risk of IVD in APOC3
      loss-of-function heterozygotes is mediated by low plasma remnant cholesterol and
      LDL-C. APPROACH AND RESULTS: In APOC3 loss-of-function heterozygotes versus
      noncarriers, we first determined remnant cholesterol and LDL-C levels in meta
      analyses of 137 895 individuals. Second, we determined whether the association
      with LDL-C was masked by lipid-lowering therapy. Finally, using mediation
      analysis, we determined the fraction of the low risk of IVD and ischemic heart
      disease mediated by remnant cholesterol and LDL-C. In meta-analyses, remnant
      cholesterol was 43% lower (95% confidence interval, 40%-47%), and LDL-C was 4%
      lower (1%-6%) in loss-of-function heterozygotes (n=776) versus noncarriers. In
      the general population, LDL-C was 3% lower in loss-of-function heterozygotes
      versus noncarriers, 4% lower when correcting for lipid-lowering therapy, and 3%
      lower in untreated individuals (P values, 0.06-0.008). Remnant cholesterol
      mediated 37% of the observed 41% lower risk of IVD and 54% of the observed 36%
      lower risk of ischemic heart disease; corresponding values mediated by LDL-C were
      1% and 2%. CONCLUSIONS: The low risk of IVD observed in APOC3 loss-of-function
      heterozygotes is mainly mediated by the associated low remnant cholesterol and
      not by low LDL-C. Furthermore, the contribution of LDL-C to IVD risk was not
      masked by lipid-lowering therapy. This suggests APOC3 and remnant cholesterol as
      important new targets for reducing cardiovascular risk.

PMID- 29348119
TI  - Cigarette Smoke Initiates Oxidative Stress-Induced Cellular Phenotypic Modulation
      Leading to Cerebral Aneurysm Pathogenesis.
AB  - OBJECTIVE: Cigarette smoke exposure (CSE) is a risk factor for cerebral aneurysm
      (CA) formation, but the molecular mechanisms are unclear. Although CSE is known
      to contribute to excess reactive oxygen species generation, the role of oxidative
      stress on vascular smooth muscle cell (VSMC) phenotypic modulation and
      pathogenesis of CAs is unknown. The goal of this study was to investigate whether
      CSE activates a NOX (NADPH oxidase)-dependent pathway leading to VSMC phenotypic
      modulation and CA formation and rupture. APPROACH AND RESULTS: In cultured
      cerebral VSMCs, CSE increased expression of NOX1 and reactive oxygen species
      which preceded upregulation of proinflammatory/matrix remodeling genes (MCP-1,
      MMPs [matrix metalloproteinase], TNF-alpha, IL-1beta, NF-kappaB, KLF4 [Kruppel
      like factor 4]) and downregulation of contractile genes (SM-alpha-actin [smooth
      muscle alpha actin], SM-22alpha [smooth muscle 22alpha], SM-MHC [smooth muscle
      myosin heavy chain]) and myocardin. Inhibition of reactive oxygen species
      production and knockdown of NOX1 with siRNA or antisense decreased CSE-induced
      upregulation of NOX1 and inflammatory genes and downregulation of VSMC
      contractile genes and myocardin. p47phox-/- NOX knockout mice, or pretreatment
      with the NOX inhibitor, apocynin, significantly decreased CA formation and
      rupture compared with controls. NOX1 protein and mRNA expression were similar in
      p47phox-/- mice and those pretreated with apocynin but were elevated in
      unruptured and ruptured CAs. CSE increased CA formation and rupture, which was
      diminished with apocynin pretreatment. Similarly, NOX1 protein and mRNA and
      reactive oxygen species were elevated by CSE, and in unruptured and ruptured CAs.
      CONCLUSIONS: CSE initiates oxidative stress-induced phenotypic modulation of
      VSMCs and CA formation and rupture. These molecular changes implicate oxidative
      stress in the pathogenesis of CAs and may provide a potential target for future
      therapeutic strategies.

PMID- 29348122
TI  - Macrophage Transitions in Heart Valve Development and Myxomatous Valve Disease.
AB  - OBJECTIVE: Hematopoietic-derived cells have been reported in heart valves but
      remain poorly characterized. Interestingly, recent studies reveal infiltration of
      leukocytes and increased macrophages in human myxomatous mitral valves.
      Nevertheless, timing and contribution of macrophages in normal valves and
      myxomatous valve disease are still unknown. The objective is to characterize
      leukocytes during postnatal heart valve maturation and identify macrophage
      subsets in myxomatous valve disease. APPROACH AND RESULTS: Leukocytes are
      detected in heart valves after birth, and their numbers increase during postnatal
      valve development. Flow cytometry and immunostaining analysis indicate that
      almost all valve leukocytes are myeloid cells, consisting of at least 2
      differentially localized macrophage subsets and dendritic cells. Beginning a week
      after birth, increased numbers of CCR2+ (C-C chemokine receptor type 2)
      macrophages are present, consistent with infiltrating populations of monocytes,
      and macrophages are localized in regions of biomechanical stress in the valve
      leaflets. Valve leukocytes maintain expression of CD (cluster of differentiation)
      45 and do not contribute to significant numbers of endothelial or interstitial
      cells. Macrophage lineages were examined in aortic and mitral valves of Axin2 KO
      (knockout) mice that exhibit myxomatous features. Infiltrating CCR2+ monocytes
      and expansion of CD206-expressing macrophages are localized in regions where
      modified heavy chain hyaluronan is observed in myxomatous valve leaflets. Similar
      colocalization of modified hyaluronan and increased numbers of macrophages were
      observed in human myxomatous valve disease. CONCLUSIONS: Our study demonstrates
      the heterogeneity of myeloid cells in heart valves and highlights an alteration
      of macrophage subpopulations, notably an increased presence of infiltrating CCR2+
      monocytes and CD206+ macrophages, in myxomatous valve disease.

PMID- 29348121
TI  - Endothelial Cell-Derived Von Willebrand Factor, But Not Platelet-Derived,
      Promotes Atherosclerosis in Apolipoprotein E-Deficient Mice.
AB  - OBJECTIVE: VWF (von Willebrand factor) is synthesized by endothelial cells and
      megakaryocytes and is known to contribute to atherosclerosis. In vitro studies
      suggest that platelet-derived VWF (Plt-VWF) is biochemically and functionally
      different from endothelial cell-derived VWF (EC-VWF). We determined the role of
      different pools of VWF in the pathophysiology of atherosclerosis. APPROACH AND
      RESULTS: Using bone marrow transplantation, we generated chimeric Plt-VWF, EC
      VWF, and Plt-VWF mice lacking a disintegrin and metalloprotease with
      thrombospondin type I repeats-13 in platelets and plasma on apolipoprotein E
      deficient (Apoe-/-) background. Controls were chimeric Apoe-/- mice transplanted
      with bone marrow from Apoe-/- mice (wild type) and Vwf-/-Apoe-/- mice
      transplanted with bone marrow from Vwf-/-Apoe-/- mice (VWF-knock out).
      Susceptibility to atherosclerosis was evaluated in whole aortae and cross
      sections of the aortic sinus in female mice fed a high-fat Western diet for 14
      weeks. VWF-knock out, Plt-VWF, and Plt-VWF mice lacking a disintegrin and
      metalloprotease with thrombospondin type I repeats-13 exhibited reduced plaque
      size characterized by smaller necrotic cores, reduced neutrophil and
      monocytes/macrophages content, decreased MMP9 (matrix metalloproteinase), MMP2,
      and CX3CL1 (chemokine [C-X3-C motif] ligand 1)-positive area, and abundant
      interstitial collagen (P<0.05 versus wild-type or EC-VWF mice). Atherosclerotic
      lesion size and composition were comparable between wild-type or EC-VWF mice.
      Together these findings suggest that EC-VWF, but not Plt-VWF, promotes
      atherosclerosis exacerbation. Furthermore, intravital microscopy experiments
      revealed that EC-VWF, but not Plt-VWF, contributes to platelet and leukocyte
      adhesion under inflammatory conditions at the arterial shear rate. CONCLUSIONS:
      EC-VWF, but not Plt-VWF, contributes to VWF-dependent atherosclerosis by
      promoting platelet adhesion and vascular inflammation. Plt-VWF even in the
      absence of a disintegrin and metalloprotease with thrombospondin type I repeats
      13, both in platelet and plasma, was not sufficient to promote atherosclerosis.

PMID- 29348123
TI  - Rash associated with rivaroxaban use.
AB  - PURPOSE: A case of a patient who developed a hypersensitivity reaction to
      rivaroxaban in the form of a diffuse, exanthematous rash is reported. SUMMARY:
      After starting rivaroxaban for treatment of cancer-associated deep vein
      thrombosis (DVT) with pulmonary embolism (PE), a 69-year-old Caucasian woman
      arrived at an oncology clinic with a diffuse, exanthematous (morbilliform) rash
      on her neck and torso, spreading to her upper and lower extremities. She reported
      that the symptoms started to develop about 48 hours after transitioning from
      subcutaneous enoxaparin to oral rivaroxaban. The patient's symptoms did not
      subside with diphenhydramine 25-50 mg orally every 6-8 hours. The patient was
      switched back to enoxaparin therapy for continued anticoagulation therapy. On day
      5, rivaroxaban and diphenhydramine were discontinued. Oral dexamethasone 4 mg
      twice daily was initiated, and the patient transitioned from rivaroxaban to
      enoxaparin 1 mg/kg every 12 hours subcutaneously. On day 8, the rash had
      diminished considerably and was present only on her thighs. Analysis of the case
      using the adverse drug reaction probability scale of Naranjo et al. indicated
      that rivaroxaban was the probable cause of the hypersensitivity reaction. Four
      prior case reports of rivaroxaban hypersensitivity manifesting as a rash have
      been previously reported, with this being the first in a female and the first in
      a patient undergoing treatment of DVT and PE in the setting of active cancer.
      CONCLUSION: A 69-year-old Caucasian woman developed a diffuse, exanthematous rash
      on day 3 of rivaroxaban treatment. Symptoms abated after rivaroxaban
      discontinuation and treatment with dexamethasone.

PMID- 29348124
TI  - Organic Anion Transporting Polypeptide 1a4 is Responsible for the Hepatic Uptake
      of Cardiac Glycosides in Mice.
AB  - Among organic anion transporting polypeptide (Oatp) family transporters expressed
      in the rodent liver, such as Oatp1a1, Oatp1a4, Oatp1b2, and Oatp2b1, Oatp1a4 has
      a unique character to recognize neutral cardiac glycosides as a substrate in
      addition to organic anions. The relative contribution of Oatp1a4 to the substrate
      uptake into hepatocytes has not been clarified. In this study, we investigated
      the importance of Oatp1a4 in the hepatic uptake of its substrate drugs using
      Slco1a4-/- mice. The hepatic mRNA expression of Slco1a4 was decreased
      significantly in Slco1a4-/- mice, whereas no differences were seen in other
      hepatic transporters between wild-type and Slco1a4-/- mice. We determined the
      plasma concentrations and liver-to-plasma concentration ratios (Kp,liver) of
      Oatp1a4 substrates, including ouabain, digoxin, BQ-123, fexofenadine,
      rosuvastatin, pravastatin, nafcillin, and telmisartan, after continuous
      intravenous infusion. The plasma concentrations of ouabain and rosuvastatin were
      2.1-fold and 1.7-fold higher in Slco1a4-/- mice, and Kp,liver of ouabain and
      digoxin were 13.4-fold and 4.3-fold lower in Slco1a4-/- mice, respectively.
      Furthermore, the biliary clearance of ouabain and digoxin with regard to plasma
      concentration were 21.9-fold and 4.1-fold lower in Slco1a4-/- mice, respectively,
      accompanied with a marked reduction in their Kp,liver, whereas the systemic
      clearance of ouabain, but not digoxin, was reduced significantly in Slco1a4-/-
      mice. These results suggest that Oatp1a4 plays a major role in the hepatic
      accumulation of cardiac glycosides in mice.

PMID- 29348125
TI  - Metabolism and Disposition of a Novel Selective alpha7 Neuronal Acetylcholine
      Receptor Agonist ABT-126 in Humans: Characterization of the Major Roles for
      Flavin-Containing Monooxygenases and UDP-Glucuronosyl Transferase 1A4 and 2B10 in
      Catalysis.
AB  - Mass balance, metabolism, and excretion of ABT-126, an alpha7 neuronal
      acetylcholine receptor agonist, were characterized in healthy male subjects (n =
      4) after a single 100-mg (100 MUCi) oral dose. The total recovery of the
      administered radioactivity was 94.0% (+/-2.09%), with 81.5% (+/-10.2%) in urine
      and 12.4% (+/-9.3%) in feces. Metabolite profiling indicated that ABT-126 had
      been extensively metabolized, with 6.6% of the dose remaining as unchanged parent
      drug in urine. Parent drug accounted for 12.2% of the administered radioactivity
      in feces. The primary metabolic transformations of ABT-126 involved aza
      adamantane N-oxidation (M1, 50.3% in urine) and aza-adamantane N-glucuronidation
      (M11, 19.9% in urine). M1 and M11 were also major circulating metabolites,
      accounting for 32.6% and 36.6% of the drug-related material in plasma,
      respectively. These results demonstrated that ABT-126 is eliminated primarily by
      hepatic metabolism, followed by urinary excretion. Enzymatic studies suggested
      that M1 formation is mediated primarily by human liver flavin-containing
      monooxygenase (FMO)3 and, to a lesser extent, by human kidney FMO1; M11 is
      generated mainly by human uridine 5'-diphospho-glucuronosyltransferase (UGT) 1A4,
      whereas UGT 2B10 also contributes to ABT-126 glucuronidation. Species-dependent
      formation of M11 was observed in hepatocytes; M11 was formed in human and monkey
      hepatocytes, but not in rat and dog hepatocytes, suggesting that monkeys
      constitute an appropriate model for predicting the fate of compounds undergoing
      significant N-glucuronidation. M1 and M11 are not expected to have clinically
      relevant on- or off-target pharmacologic activities. In summary, this study
      characterized ABT-126 metabolites in the circulation and excreta and the primary
      elimination pathways of ABT-126 in humans.

PMID- 29348126
TI  - Concerns about composite reference standards in diagnostic research.

PMID- 29348127
TI  - Murine chronic graft-versus-host disease proteome profiling discovers CCL15 as a
      novel biomarker in patients.
AB  - Improved diagnostic and treatment methods are needed for chronic graft-versus
      host disease (cGVHD), the leading cause of late nonrelapse mortality (NRM) in
      long-term survivors of allogenic hematopoietic cell transplantation. Validated
      biomarkers that facilitate disease diagnosis and classification generally are
      lacking in cGVHD. Here, we conducted whole serum proteomics analysis of a well
      established murine multiorgan system cGVHD model. We discovered 4 upregulated
      proteins during cGVHD that are targetable by genetic ablation or blocking
      antibodies, including the RAS and JUN kinase activator, CRKL, and CXCL7, CCL8,
      and CCL9 chemokines. Donor T cells lacking CRK/CRKL prevented the generation of
      cGVHD, germinal center reactions, and macrophage infiltration seen with wild-type
      T cells. Whereas antibody blockade of CCL8 or CXCL7 was ineffective in treating
      cGVHD, CCL9 blockade reversed cGVHD clinical manifestations, histopathological
      changes, and immunopathological hallmarks. Mechanistically, elevated CCL9
      expression was present predominantly in vascular smooth muscle cells and uniquely
      seen in cGVHD mice. Plasma concentrations of CCL15, the human homolog of mouse
      CCL9, were elevated in a previously published cohort of 211 cGVHD patients
      compared with controls and associated with NRM. In a cohort of 792 patients,
      CCL15 measured at day +100 could not predict cGVHD occurring within the next 3
      months with clinically relevant sensitivity/specificity. Our findings demonstrate
      for the first time the utility of preclinical proteomics screening to identify
      potential new targets for cGVHD and specifically CCL15 as a diagnosis marker for
      cGVHD. These data warrant prospective biomarker validation studies.

PMID- 29348129
TI  - Genomic CDKN2A/2B deletions in adult Ph+ ALL are adverse despite allogeneic stem
      cell transplantation.
AB  - We investigated the role of copy number alterations to refine risk stratification
      in adult Philadelphia chromosome positive (Ph)+ acute lymphoblastic leukemia
      (ALL) treated with tyrosine kinase inhibitors (TKIs) and allogeneic stem cell
      transplantation (aSCT). Ninety-seven Ph+ ALL patients (median age 41 years; range
      18-64 years) within the prospective multicenter German Multicenter ALL Study
      Group studies 06/99 (n = 8) and 07/2003 (n = 89) were analyzed. All patients
      received TKI and aSCT in first complete remission (CR1). Copy number analysis was
      performed with single nucleotide polymorphism arrays and validated by multiplex
      ligation-dependent probe amplification. The frequencies of recurrently deleted
      genes were: IKZF1, 76%; CDKN2A/2B, 45%; PAX5, 43%; BTG1, 18%; EBF1, 13%; ETV6,
      5%; RB, 14%. In univariate analyses, the presence of CDKN2A/2B deletions had a
      negative impact on all endpoints: overall survival (P = .023), disease-free
      survival (P = .012), and remission duration (P = .036). The negative predictive
      value of CDKN2A/2B deletions was retained in multivariable analysis along with
      other factors such as timing of TKI therapy, intensity of conditioning, achieving
      remission after induction phase 1 and BTG1 deletions. We therefore conclude that
      acquired genomic CDKN2A/2B deletions identify a subgroup of Ph+ ALL patients, who
      have an inferior prognosis despite aSCT in CR1. Their poor outcome was
      attributable primarily to a high relapse rate after aSCT.

PMID- 29348128
TI  - Pevonedistat, a first-in-class NEDD8-activating enzyme inhibitor, combined with
      azacitidine in patients with AML.
AB  - Pevonedistat (TAK-924/MLN4924) is a novel inhibitor of NEDD8-activating enzyme
      (NAE) with single-agent activity in relapsed/refractory acute myeloid leukemia
      (AML). We performed a phase 1b study of pevonedistat (PEV) with azacitidine (AZA)
      based on synergistic activity seen preclinically. Primary objectives included
      safety and tolerability, and secondary objectives included pharmacokinetics (PK)
      and disease response. Patients >=60 years with treatment-naive AML (unfit for
      standard induction therapy) received PEV 20 or 30 mg/m2 IV on days 1, 3, and 5
      combined with fixed-dose AZA (75 mg/m2 IV/subcutaneously) on days 1 to 5, 8, and
      9, every 28 days. The most common treatment-emergent adverse events were
      constipation (48%), nausea (42%), fatigue (42%), and anemia (39%). In total, 11
      deaths were observed and considered unrelated to study therapy by the
      investigators. Transient elevations in aspartate aminotransferase (AST) and
      alanine aminotransferase (ALT) were dose limiting. The recommended phase 2 dose
      (RP2D) of PEV in this combination is 20 mg/m2 PEV PK was not altered by the
      addition of AZA. Overall response rate (ORR) based on an intent-to-treat analysis
      was 50% (20 complete remissions [CRs], 5 complete remission with incomplete
      peripheral count recovery, 7 partial remissions [PRs]), with an 8.3-month median
      duration of remission. In patients receiving >=6 cycles of therapy (n = 23, 44%),
      ORR was 83%. In patients with TP53 mutations, the composite CR/PR rate was 80%
      (4/5). Two of these patients stayed on study for >10 cycles. Baseline bone marrow
      blast percentage or cytogenetic/molecular risk did not influence ORR. This study
      was registered at www.clinicaltrials.gov as #NCT01814826.

PMID- 29348130
TI  - SETD1A protects HSCs from activation-induced functional decline in vivo.
AB  - The regenerative capacity of hematopoietic stem cells (HSCs) is limited by the
      accumulation of DNA damage. Conditional mutagenesis of the histone 3 lysine 4
      (H3K4) methyltransferase, Setd1a, revealed that it is required for the expression
      of DNA damage recognition and repair pathways in HSCs. Specific deletion of
      Setd1a in adult long-term (LT) HSCs is compatible with adult life and has little
      effect on the maintenance of phenotypic LT-HSCs in the bone marrow. However,
      SETD1A-deficient LT-HSCs lose their transcriptional cellular identity,
      accompanied by loss of their proliferative capacity and stem cell function under
      replicative stress in situ and after transplantation. In response to inflammatory
      stimulation, SETD1A protects HSCs and progenitors from activation-induced
      attrition in vivo. The comprehensive regulation of DNA damage responses by SETD1A
      in HSCs is clearly distinct from the key roles played by other epigenetic
      regulators, including the major leukemogenic H3K4 methyltransferase MLL1, or
      MLL5, indicating that HSC identity and function is supported by cooperative
      specificities within an epigenetic framework.

PMID- 29348131
TI  - Iodine Extravasation Quantification on Dual-Energy CT of the Brain Performed
      after Mechanical Thrombectomy for Acute Ischemic Stroke Can Predict Hemorrhagic
      Complications.
AB  - BACKGROUND AND PURPOSE: Intracerebral hemorrhage represents a potentially severe
      complication of revascularization of acute ischemic stroke. The aim of our study
      was to assess the capability of iodine extravasation quantification on dual
      energy CT performed immediately after mechanical thrombectomy to predict
      hemorrhagic complications. MATERIALS AND METHODS: Because this was a
      retrospective study, the need for informed consent was waived. Eighty-five
      consecutive patients who underwent brain dual-energy CT immediately after
      mechanical thrombectomy for acute ischemic stroke between August 2013 and January
      2017 were included. Two radiologists independently evaluated dual-energy CT
      images for the presence of parenchymal hyperdensity, iodine extravasation, and
      hemorrhage. Maximum iodine concentration was measured. Follow-up CT examinations
      performed until patient discharge were reviewed for intracerebral hemorrhage
      development. The correlation between dual-energy CT parameters and intracerebral
      hemorrhage development was analyzed by the Mann-Whitney U test and Fisher exact
      test. Receiver operating characteristic curves were generated for continuous
      variables. RESULTS: Thirteen of 85 patients (15.3%) developed hemorrhage. On
      postoperative dual-energy CT, parenchymal hyperdensities and iodine extravasation
      were present in 100% of the patients who developed intracerebral hemorrhage and
      in 56.3% of the patients who did not (P = .002 for both). Signs of bleeding were
      present in 35.7% of the patients who developed intracerebral hemorrhage and in
      none of the patients who did not (P < .001). Median maximum iodine concentration
      was 2.63 mg/mL in the patients who developed intracerebral hemorrhage and 1.4
      mg/mL in the patients who did not (P < .001). Maximum iodine concentration showed
      an area under the curve of 0.89 for identifying patients developing intracerebral
      hemorrhage. CONCLUSIONS: The presence of parenchymal hyperdensity with a maximum
      iodine concentration of >1.35 mg/mL may identify patients developing
      intracerebral hemorrhage with 100% sensitivity and 67.6% specificity.

PMID- 29348132
TI  - T2 Relaxometry MRI Predicts Cerebral Palsy in Preterm Infants.
AB  - BACKGROUND AND PURPOSE: T2-relaxometry brain MR imaging enables objective
      measurement of brain maturation based on the water-macromolecule ratio in white
      matter, but the outcome correlation is not established in preterm infants. Our
      study aimed to predict neurodevelopment with T2-relaxation values of brain MR
      imaging among preterm infants. MATERIALS AND METHODS: From January 1, 2012, to
      May 31, 2015, preterm infants who underwent both T2-relaxometry brain MR imaging
      and neurodevelopmental follow-up were retrospectively reviewed. T2-relaxation
      values were measured over the periventricular white matter, including sections
      through the frontal horns, midbody of the lateral ventricles, and centrum
      semiovale. Periventricular T2 relaxometry in relation to corrected age was
      analyzed with restricted cubic spline regression. Prediction of cerebral palsy
      was examined with the receiver operating characteristic curve. RESULTS: Thirty
      eight preterm infants were enrolled for analysis. Twenty patients (52.6%) had
      neurodevelopmental abnormalities, including 8 (21%) with developmental delay
      without cerebral palsy and 12 (31.6%) with cerebral palsy. The periventricular T2
      relaxation values in relation to age were curvilinear in preterm infants with
      normal development, linear in those with developmental delay without cerebral
      palsy, and flat in those with cerebral palsy. When MR imaging was performed at >1
      month corrected age, cerebral palsy could be predicted with T2 relaxometry of the
      periventricular white matter on sections through the midbody of the lateral
      ventricles (area under the receiver operating characteristic curve = 0.738;
      cutoff value of >217.4 with 63.6% sensitivity and 100.0% specificity).
      CONCLUSIONS: T2-relaxometry brain MR imaging could provide prognostic prediction
      of neurodevelopmental outcomes in premature infants. Age-dependent and area
      selective interpretation in preterm brains should be emphasized.

PMID- 29348133
TI  - Review of the Imaging Features of Benign Osteoporotic and Malignant Vertebral
      Compression Fractures.
AB  - Vertebral compression fractures are very common, especially in the elderly.
      Benign osteoporotic and malignant vertebral compression fractures have extremely
      different management and prognostic implications. Although there is an overlap in
      appearances, characteristic imaging features can aid in the distinction between
      these 2 types of compression fractures. The aim of this review is to characterize
      the imaging features of benign and malignant vertebral compression fractures seen
      with CT, PET, SPECT, and MR imaging.

PMID- 29348134
TI  - Cerebral Mitochondrial Microangiopathy Leads to Leukoencephalopathy in
      Mitochondrial Neurogastrointestinal Encephalopathy.
AB  - BACKGROUND AND PURPOSE: Mitochondrial neurogastrointestinal encephalopathy is a
      rare disorder due to recessive mutations in the thymidine phosphorylase gene,
      encoding thymidine phosphorylase protein required for mitochondrial DNA
      replication. Clinical manifestations include gastrointestinal dysmotility and
      diffuse asymptomatic leukoencephalopathy. This study aimed to elucidate the
      mechanisms underlying brain leukoencephalopathy in patients with mitochondrial
      neurogastrointestinal encephalopathy by correlating multimodal neuroradiologic
      features to postmortem pathology. MATERIALS AND METHODS: Seven patients underwent
      brain MR imaging, including single-voxel proton MR spectroscopy and diffusion
      imaging. Absolute concentrations of metabolites calculated by acquiring
      unsuppressed water spectra at multiple TEs, along with diffusion metrics based on
      the tensor model, were compared with those of healthy controls using unpaired t
      tests in multiple white matters regions. Brain postmortem histologic,
      immunohistochemical, and molecular analyses were performed in 1 patient. RESULTS:
      All patients showed bilateral and nearly symmetric cerebral white matter
      hyperintensities on T2-weighted images, extending to the cerebellar white matter
      and brain stem in 4. White matter, N-acetylaspartate, creatine, and choline
      concentrations were significantly reduced compared with those in controls, with a
      prominent increase in the radial water diffusivity component. At postmortem
      examination, severe fibrosis of brain vessel smooth muscle was evident, along
      with mitochondrial DNA replication depletion in brain and vascular smooth-muscle
      and endothelial cells, without neuronal loss, myelin damage, or gliosis.
      Prominent periependymal cytochrome C oxidase deficiency was also observed.
      CONCLUSIONS: Vascular functional and histologic alterations account for
      leukoencephalopathy in mitochondrial neurogastrointestinal encephalopathy.
      Thymidine toxicity and mitochondrial DNA replication depletion may induce
      microangiopathy and blood-brain-barrier dysfunction, leading to increased water
      content in the white matter. Periependymal cytochrome C oxidase deficiency could
      explain prominent periventricular impairment.

PMID- 29348135
TI  - Development of High Signal Intensity within the Globus Pallidus and Dentate
      Nucleus following Multiple Administrations of Gadobenate Dimeglumine.
AB  - BACKGROUND AND PURPOSE: Previous studies have evaluated various gadolinium based
      contrast agents and their association with gadolinium retention, however, there
      is a discrepancy in the literature concerning the linear agent gadobenate
      dimeglumine. Our aim was to determine whether an association exists between the
      administration of gadobenate dimeglumine and the development of intrinsic T1
      weighted signal in the dentate nucleus and globus pallidus. MATERIALS AND
      METHODS: In this single-center, retrospective study, the signal intensity of the
      globus pallidus, dentate nucleus, thalamus, and middle cerebellar peduncle was
      measured on unenhanced T1-weighted images in 29 adult patients who had undergone
      multiple contrast MRIs using exclusively gadobenate dimeglumine (mean, 10.1 +/-
      3.23 doses; range, 6-18 doses). Two neuroradiologists, blinded to the number of
      prior gadolinium-based contrast agent administrations, separately placed ROIs
      within the globi pallidi, thalami, dentate nuclei, and middle cerebellar
      peduncles on the last MR imaging examinations. The correlations between the
      globus pallidus:thalamus and the dentate nucleus:middle cerebellar peduncle
      signal intensity ratios with the number of gadolinium-based contrast agent
      administrations and cumulative dose were tested with either 1-tailed Pearson or
      Spearman correlations. A priori, P < .05 was considered statistically
      significant. RESULTS: Both the globus pallidus:thalamus and dentate
      nucleus:middle cerebellar peduncle ratios showed significant correlation with the
      number of gadolinium-based contrast agent administrations (r = 0.39, P = .017,
      and r = 0.58, P = .001, respectively). Additionally, the globus pallidus:thalamus
      and dentate nucleus:middle cerebellar peduncle ratios showed significant
      correlation with the cumulative dose of gadobenate dimeglumine (r = 0.48, P =
      .004, and r = 0.43, P = .009, respectively). Dentate nucleus hyperintensity was
      qualitatively present on the last MR imaging in 79.3%-86.2% of patients and in
      all patients who had received >10 doses. CONCLUSIONS: At high cumulative doses
      (commonly experienced by patients, for example, with neoplastic disease),
      gadobenate dimeglumine is associated with an increase in the globus
      pallidus:thalamus and dentate nucleus:middle cerebellar peduncles signal
      intensity ratios.

PMID- 29348137
TI  - Accuracy of the Compressed Sensing Accelerated 3D-FLAIR Sequence for the
      Detection of MS Plaques at 3T.
AB  - BACKGROUND AND PURPOSE: The use of 3D FLAIR improves the detection of brain
      lesions in MS patients, but requires long acquisition times. Compressed sensing
      reduces acquisition time by using the sparsity of MR images to randomly
      undersample the k-space. Our aim was to compare the image quality and diagnostic
      performance of 3D-FLAIR with and without compressed sensing for the detection of
      multiple sclerosis lesions at 3T. MATERIALS AND METHODS: Twenty-three patients
      with relapsing-remitting MS underwent both conventional 3D-FLAIR and compressed
      sensing 3D-FLAIR on a 3T scanner (reduction in scan time 1 minute 25 seconds,
      27%; compressed sensing factor of 1.3). Two blinded readers independently
      evaluated both conventional and compressed sensing FLAIR for image quality (SNR
      and contrast-to-noise ratio) and the number of MS lesions visible in the
      periventricular, intra-juxtacortical, infratentorial, and optic nerve regions.
      The volume of white matter lesions was measured with automatic postprocessing
      segmentation software for each FLAIR sequence. RESULTS: Image quality and the
      number of MS lesions detected by the readers were similar between the 2 FLAIR
      acquisitions (P = .74 and P = .094, respectively). Almost perfect agreement was
      found between both FLAIR acquisitions for total MS lesion count (Lin concordance
      correlation coefficient = 0.99). Agreement between conventional and compressed
      sensing FLAIR was almost perfect for periventricular and infratentorial lesions
      and substantial for intrajuxtacortical and optic nerve lesions. Postprocessing
      with the segmentation software did not reveal a significant difference between
      conventional and compressed sensing FLAIR in total MS lesion volume (P = .63) or
      the number of MS lesions (P = .15). CONCLUSIONS: With a compressed sensing factor
      of 1.3, 3D-FLAIR is 27% faster and preserves diagnostic performance for the
      detection of MS plaques at 3T.

PMID- 29348136
TI  - Resting-State Functional MRI: Everything That Nonexperts Have Always Wanted to
      Know.
AB  - Resting-state fMRI was first described by Biswal et al in 1995 and has since then
      been widely used in both healthy subjects and patients with various neurologic,
      neurosurgical, and psychiatric disorders. As opposed to paradigm- or task-based
      functional MR imaging, resting-state fMRI does not require subjects to perform
      any specific task. The low-frequency oscillations of the resting-state fMRI
      signal have been shown to relate to the spontaneous neural activity. There are
      many ways to analyze resting-state fMRI data. In this review article, we will
      briefly describe a few of these and highlight the advantages and limitations of
      each. This description is to facilitate the adoption and use of resting-state
      fMRI in the clinical setting, helping neuroradiologists become familiar with
      these techniques and applying them for the care of patients with neurologic and
      psychiatric diseases.

PMID- 29348138
TI  - Development and validation of outcome prediction models for aneurysmal
      subarachnoid haemorrhage: the SAHIT multinational cohort study.
AB  - OBJECTIVE: To develop and validate a set of practical prediction tools that
      reliably estimate the outcome of subarachnoid haemorrhage from ruptured
      intracranial aneurysms (SAH). DESIGN: Cohort study with logistic regression
      analysis to combine predictors and treatment modality. SETTING: Subarachnoid
      Haemorrhage International Trialists' (SAHIT) data repository, including
      randomised clinical trials, prospective observational studies, and hospital
      registries. PARTICIPANTS: Researchers collaborated to pool datasets of
      prospective observational studies, hospital registries, and randomised clinical
      trials of SAH from multiple geographical regions to develop and validate clinical
      prediction models. MAIN OUTCOME MEASURE: Predicted risk of mortality or
      functional outcome at three months according to score on the Glasgow outcome
      scale. RESULTS: Clinical prediction models were developed with individual patient
      data from 10 936 patients and validated with data from 3355 patients after
      development of the model. In the validation cohort, a core model including
      patient age, premorbid hypertension, and neurological grade on admission to
      predict risk of functional outcome had good discrimination, with an area under
      the receiver operator characteristics curve (AUC) of 0.80 (95% confidence
      interval 0.78 to 0.82). When the core model was extended to a "neuroimaging
      model," with inclusion of clot volume, aneurysm size, and location, the AUC
      improved to 0.81 (0.79 to 0.84). A full model that extended the neuroimaging
      model by including treatment modality had AUC of 0.81 (0.79 to 0.83).
      Discrimination was lower for a similar set of models to predict risk of mortality
      (AUC for full model 0.76, 0.69 to 0.82). All models showed satisfactory
      calibration in the validation cohort. CONCLUSION: The prediction models reliably
      estimate the outcome of patients who were managed in various settings for
      ruptured intracranial aneurysms that caused subarachnoid haemorrhage. The
      predictor items are readily derived at hospital admission. The web based SAHIT
      prognostic calculator (http://sahitscore.com) and the related app could be
      adjunctive tools to support management of patients.

PMID- 29348139
TI  - Dissecting the functions of SMG5, SMG7, and PNRC2 in nonsense-mediated mRNA decay
      of human cells.
AB  - The term "nonsense-mediated mRNA decay" (NMD) originally described the
      degradation of mRNAs with premature translation-termination codons (PTCs), but
      its meaning has recently been extended to be a translation-dependent post
      transcriptional regulator of gene expression affecting 3%-10% of all mRNAs. The
      degradation of NMD target mRNAs involves both exonucleolytic and endonucleolytic
      pathways in mammalian cells. While the latter is mediated by the endonuclease
      SMG6, the former pathway has been reported to require a complex of SMG5-SMG7 or
      SMG5-PNRC2 binding to UPF1. However, the existence, dominance, and mechanistic
      details of these exonucleolytic pathways are divisive. Therefore, we have
      investigated the possible exonucleolytic modes of mRNA decay in NMD by examining
      the roles of UPF1, SMG5, SMG7, and PNRC2 using a combination of functional assays
      and interaction mapping. Confirming previous work, we detected an interaction
      between SMG5 and SMG7 and also a functional need for this complex in NMD. In
      contrast, we found no evidence for the existence of a physical or functional
      interaction between SMG5 and PNRC2. Instead, we show that UPF1 interacts with
      PNRC2 and that it triggers 5'-3' exonucleolytic decay of reporter transcripts in
      tethering assays. PNRC2 interacts mainly with decapping factors and its knockdown
      does not affect the RNA levels of NMD reporters. We conclude that PNRC2 is
      probably an important mRNA decapping factor but that it does not appear to be
      required for NMD.

PMID- 29348140
TI  - Interactions, localization, and phosphorylation of the m6A generating METTL3
      METTL14-WTAP complex.
AB  - N6-methyladenine (m6A) is found on many eukaryotic RNAs including mRNAs. m6A
      modification has been implicated in mRNA stability and turnover, localization, or
      translation efficiency. A heterodimeric enzyme complex composed of METTL3 and
      METTL14 generates m6A on mRNAs. METTL3/14 is found in the nucleus where it is
      localized to nuclear speckles and the splicing regulator WTAP is required for
      this distinct nuclear localization pattern. Although recent crystal structures
      revealed how the catalytic MT-A70 domains of METTL3 and METTL14 interact with
      each other, a more global architecture including WTAP and RNA interactions has
      not been reported so far. Here, we used recombinant proteins and mapped binding
      surfaces within the METTL3/14-WTAP complex. Furthermore, we identify nuclear
      localization signals and identify phosphorylation sites on the endogenous
      proteins. Using an in vitro methylation assay, we confirm that monomeric METTL3
      is soluble and inactive while the catalytic center of METTL14 is degenerated and
      thus also inactive. In addition, we show that the C-terminal RGG repeats of
      METTL14 are required for METTL3/14 activity by contributing to RNA substrate
      binding. Our biochemical work identifies characteristic features of METTL3/14
      WTAP and reveals novel insight into the overall architecture of this important
      enzyme complex.

PMID- 29348141
TI  - CELLULASE6 and MANNANASE7 Affect Cell Differentiation and Silique Dehiscence.
AB  - Cellulases, hemicellulases, and pectinases play important roles in fruit
      development and maturation. Although mutants with defects in these processes have
      not been reported for cellulase or hemicellulase genes, the pectinases
      ARABIDOPSIS DEHISCENCE ZONE POLYGALACTURONASE1 (ADPG1) and ADPG2 were previously
      shown to be essential for silique dehiscence in Arabidopsis (Arabidopsis
      thaliana). Here, we demonstrate that the cellulase gene CELLULASE6 (CEL6) and the
      hemicellulase gene MANNANASE7 (MAN7) function in the development and dehiscence
      of Arabidopsis siliques. We found that these genes were expressed in both
      vegetative and reproductive organs and that their expression in the silique
      partially depended on the INDEHISCENT and ALCATRAZ transcription factors. Cell
      differentiation was delayed in the dehiscence zone of cel6 and man7 mutant
      siliques at early flower development stage 17, and a comparison of the spatio
      temporal patterns of CEL6 and MAN7 expression with the locations of delayed cell
      differentiation in the cel6 and man7 mutants revealed that CEL6 and MAN7 likely
      indirectly affect the timing of cell differentiation in the silique valve at this
      stage. CEL6 and MAN7 were also found to promote cell degeneration in the
      separation layer in nearly mature siliques, as cells in this layer remained
      intact in the cel6 and man7 mutants and the cel6-1 man7-3 double mutant, whereas
      they degenerated in the wild-type control. Phenotypic studies of single, double,
      triple, and quadruple mutants revealed that higher-order mutant combinations of
      cel6-1, man7-3, and adpg1-1 and adpg2-1 produced more severe silique indehiscent
      phenotypes than the corresponding lower-order mutant combinations, except for
      some combinations involving cel6-1, man7-3, and adpg2-1 Our results demonstrate
      that the ability of the silique to dehisce can be manipulated to different
      degrees by altering the activities of various cell wall-modifying enzymes.

PMID- 29348142
TI  - SEMA3C drives cancer growth by transactivating multiple receptor tyrosine kinases
      via Plexin B1.
AB  - Growth factor receptor tyrosine kinase (RTK) pathway activation is a key
      mechanism for mediating cancer growth, survival, and treatment resistance.
      Cognate ligands play crucial roles in autocrine or paracrine stimulation of these
      RTK pathways. Here, we show SEMA3C drives activation of multiple RTKs including
      EGFR, ErbB2, and MET in a cognate ligand-independent manner via Plexin B1. SEMA3C
      expression levels increase in castration-resistant prostate cancer (CRPC), where
      it functions to promote cancer cell growth and resistance to androgen receptor
      pathway inhibition. SEMA3C inhibition delays CRPC and enzalutamide-resistant
      progression. Plexin B1 sema domain-containing:Fc fusion proteins suppress RTK
      signaling and cell growth and inhibit CRPC progression of LNCaP xenografts post
      castration in vivo SEMA3C inhibition represents a novel therapeutic strategy for
      treatment of advanced prostate cancer.

PMID- 29348143
TI  - Detecting Polygenic Adaptation in Admixture Graphs.
AB  - An open question in human evolution is the importance of polygenic adaptation:
      adaptive changes in the mean of a multifactorial trait due to shifts in allele
      frequencies across many loci. In recent years, several methods have been
      developed to detect polygenic adaptation using loci identified in genome-wide
      association studies (GWAS). Though powerful, these methods suffer from limited
      interpretability: they can detect which sets of populations have evidence for
      polygenic adaptation, but are unable to reveal where in the history of multiple
      populations these processes occurred. To address this, we created a method to
      detect polygenic adaptation in an admixture graph, which is a representation of
      the historical divergences and admixture events relating different populations
      through time. We developed a Markov chain Monte Carlo (MCMC) algorithm to infer
      branch-specific parameters reflecting the strength of selection in each branch of
      a graph. Additionally, we developed a set of summary statistics that are fast to
      compute and can indicate which branches are most likely to have experienced
      polygenic adaptation. We show via simulations that this method-which we call
      PolyGraph-has good power to detect polygenic adaptation, and applied it to human
      population genomic data from around the world. We also provide evidence that
      variants associated with several traits, including height, educational
      attainment, and self-reported unibrow, have been influenced by polygenic
      adaptation in different populations during human evolution.

PMID- 29348145
TI  - FBXL13 directs the proteolysis of CEP192 to regulate centrosome homeostasis and
      cell migration.
AB  - Aberrant centrosome organisation with ensuing alterations of microtubule
      nucleation capacity enables tumour cells to proliferate and invade despite
      increased genomic instability. CEP192 is a key factor in the initiation process
      of centrosome duplication and in the control of centrosome microtubule
      nucleation. However, regulatory means of CEP192 have remained unknown. Here, we
      report that FBXL13, a binding determinant of SCF (SKP1-CUL1-F-box)-family E3
      ubiquitin ligases, is enriched at centrosomes and interacts with the centrosomal
      proteins Centrin-2, Centrin-3, CEP152 and CEP192. Among these, CEP192 is
      specifically targeted for proteasomal degradation by FBXL13. Accordingly, induced
      FBXL13 expression downregulates centrosomal gamma-tubulin and disrupts
      centrosomal microtubule arrays. In addition, depletion of FBXL13 induces high
      levels of CEP192 and gamma-tubulin at the centrosomes with the consequence of
      defects in cell motility. Together, we characterise FBXL13 as a novel regulator
      of microtubule nucleation activity and highlight a role in promoting cell
      motility with potential tumour-promoting implications.

PMID- 29348146
TI  - The INs and OUTs of mitofusins.
AB  - Mitofusins are outer membrane proteins essential for mitochondrial fusion. Their
      accepted topology posits that both N and C termini face the cytoplasm. In this
      issue, Mattie et al. (2018. J. Cell Biol. https://doi.org/10.1083/jcb.201611194)
      demonstrate instead that their C termini reside in the intermembrane space. These
      findings call for a revision of the current models of mitochondrial fusion.

PMID- 29348144
TI  - A CRISPR Tagging-Based Screen Reveals Localized Players in Wnt-Directed
      Asymmetric Cell Division.
AB  - Oriented cell divisions are critical to establish and maintain cell fates and
      tissue organization. Diverse extracellular and intracellular cues have been shown
      to provide spatial information for mitotic spindle positioning; however, the
      molecular mechanisms by which extracellular signals communicate with cells to
      direct mitotic spindle positioning are largely unknown. In animal cells, oriented
      cell divisions are often achieved by the localization of force-generating motor
      protein complexes to discrete cortical domains. Disrupting either these force
      generating complexes or proteins that globally affect microtubule stability
      results in defects in mitotic positioning, irrespective of whether these proteins
      function as spatial cues for spindle orientation. This poses a challenge to
      traditional genetic dissection of this process. Therefore, as an alternative
      strategy to identify key proteins that act downstream of intercellular signaling,
      we screened the localization of many candidate proteins by inserting fluorescent
      tags directly into endogenous gene loci, without overexpressing the proteins. We
      tagged 23 candidate proteins in Caenorhabditis elegans and examined each
      protein's localization in a well-characterized, oriented cell division in the
      four-cell-stage embryo. We used cell manipulations and genetic experiments to
      determine which cells harbor key localized proteins and which signals direct
      these localizations in vivo We found that Dishevelled and adenomatous polyposis
      coli homologs are polarized during this oriented cell division in response to a
      Wnt signal, but two proteins typically associated with mitotic spindle
      positioning, homologs of NuMA and Dynein, were not detectably polarized. These
      results suggest an unexpected mechanism for mitotic spindle positioning in this
      system, they pinpoint key proteins of interest, and they highlight the utility of
      a screening approach based on analyzing the localization of endogenously tagged
      proteins.

PMID- 29348147
TI  - Bao-Liang Song: Loving biology in the time of cholesterol.
AB  - Song studies the trafficking and biological activities of cholesterol.

PMID- 29348148
TI  - Replication timing kept in LINE.
AB  - Accurate and synchronous replication timing between chromosome homologues is
      essential for maintaining chromosome stability, yet how this is achieved has
      remained a mystery. In this issue, Platt et al. (2018. J. Cell Biol.
      https://doi.org/10.1083/jcb.201707082) identify antisense LINE (L1) transcripts
      within long noncoding RNAs as the critical factor in maintaining synchronous
      chromosome-wide replication timing.

PMID- 29348150
TI  - GMC erasure case: how we learn from human error.

PMID- 29348151
TI  - AHRR hypomethylation, lung function, lung function decline and respiratory
      symptoms.
AB  - Epigenome-wide association studies have shown a consistent association between
      smoking exposure and hypomethylation in the aryl hydrocarbon receptor repressor
      (AHRR) gene (cg05575921). We tested the hypothesis that AHRR hypomethylation is
      associated with low lung function, steeper lung function decline, and respiratory
      symptoms in the general population.AHRR methylation extent was measured in 9113
      individuals from the 1991-1994 examination of the Copenhagen City Heart Study,
      using bisulfite-treated leukocyte DNA. Spirometry at the time of blood sampling
      was available for all individuals. Lung function was measured again for 4532 of
      these individuals in 2001-2003.Cross-sectionally, a 10% lower methylation extent
      was associated with a 0.2 z-score (95% CI 0.1-0.2) lower forced expiratory volume
      in 1 s (FEV1) after multivariable adjustment including smoking. Hypomethylation
      was also associated with a lower z-score for both forced vital capacity (FVC) and
      FEV1/FVC. In prospective analyses, individuals in the lowest versus highest
      tertile of methylation extent had a steeper decline in FEV1/height3 (p for
      examination*methylation interaction=0.003) and FVC/height3 (p=0.01), but not
      FEV1/FVC (p=0.08). Multivariable-adjusted odds ratios per 10% lower methylation
      extent were 1.31 (95% CI 1.18-1.45) for chronic bronchitis and 1.21 (95% CI 1.13
      1.30) for any respiratory symptoms.AHRR hypomethylation was associated with low
      lung function, steeper lung function decline, and respiratory symptoms.

PMID- 29348152
TI  - Hearing loss with kanamycin treatment for multidrug-resistant tuberculosis in
      Bangladesh.

PMID- 29348153
TI  - First histopathological evidence of irreversible pulmonary vascular disease in
      dasatinib-induced pulmonary arterial hypertension.

PMID- 29348154
TI  - Differential diagnosis between newly diagnosed asthma and COPD using exhaled
      breath condensate metabolomics: a pilot study.

PMID- 29348155
TI  - Mesenchymal stromal cell infusion modulates systemic immunological responses in
      stable COPD patients: a phase I pilot study.

PMID- 29348156
TI  - Development and feasibility of an eHealth tool for idiopathic pulmonary fibrosis.

PMID- 29348159
TI  - Correction: Introduction of allergenic foods from 3 months of age reduces
      incidence of food allergy in breastfed infants.

PMID- 29348157
TI  - GMC erasure case: we must improve systems to mitigate inevitable mistakes.

PMID- 29348160
TI  - Up all night: BK channels' circadian dance with different calcium sources.
AB  - JGP study explores diurnal changes in calcium sources governing BK activity in
      the SCN.

PMID- 29348161
TI  - CNS Metastases Needn't Rule Out Trial Inclusion.
AB  - New guidelines from an expert working group describe when to include or exclude
      patients with brain metastases from clinical trials. In the past, these patients
      have often been inappropriately excluded from trials, resulting in a dearth of
      information on the efficacy of cancer drugs in the central nervous system.

PMID- 29348162
TI  - Mutation Burden Predicts Anti-PD-1 Response.
AB  - A new study finds that objective response rates to anti-PD-1 therapies correlate
      with tumor mutation burden for most of the 27 cancer types studied. Objective
      response rates were higher than expected for Merkel cell carcinoma and renal cell
      carcinoma, which may be particularly immunogenic. The objective response rate was
      unexpectedly low for colorectal cancer with mismatch repair proficiency.

PMID- 29348163
TI  - IFCC Working Group Recommendations for Assessing Commutability Part 1: General
      Experimental Design.
AB  - Commutability is a property of a reference material (RM) that relates to the
      closeness of agreement between results for an RM and results for clinical samples
      (CSs) when measured by >=2 measurement procedures (MPs). Commutability of RMs
      used in a calibration traceability scheme is an essential property for them to be
      fit for purpose. Similarly, commutability of trueness controls or external
      quality assessment samples is essential when those materials are used to assess
      trueness of results for CSs. This report is part 1 of a 3-part series describing
      how to assess commutability of RMs. Part 1 defines commutability and addresses
      critical components of the experimental design for commutability assessment,
      including selection of individual CSs, use of pooled CSs, qualification of MPs
      for inclusion, establishing criteria for the determination that an RM is
      commutable, generalization of commutability conclusions to future measurements
      made with the MPs included in the assessment, and information regarding
      commutability to be included in the certificate for an RM. Parts 2 and 3 in the
      series present 2 different statistical approaches to commutability assessment
      that use fixed criteria related to the medical decisions that will be made using
      the laboratory test results.

PMID- 29348164
TI  - IFCC Working Group Recommendations for Assessing Commutability Part 3: Using the
      Calibration Effectiveness of a Reference Material.
AB  - A process is described to assess the commutability of a reference material (RM)
      intended for use as a calibrator based on its ability to fulfill its intended use
      in a calibration traceability scheme to produce equivalent clinical sample (CS)
      results among different measurement procedures (MPs) for the same measurand.
      Three sources of systematic error are elucidated in the context of creating the
      calibration model for translating MP signals to measurand amounts: calibration
      fit, calibrator level trueness, and commutability. An example set of 40 CS
      results from 7 MPs is used to illustrate estimation of bias and variability for
      each MP. The candidate RM is then used to recalibrate each MP, and its
      effectiveness in reducing the systematic error among the MPs within an acceptable
      level of equivalence based on medical requirements confirms its commutability for
      those MPs. The RM is declared noncommutable for MPs for which, after
      recalibration, the CS results do not agree with those from other MPs. When a lack
      of agreement is found, other potential causes, including lack of calibration fit,
      should be investigated before concluding the RM is noncommutable. The RM is
      considered fit for purpose for those MPs where commutability is demonstrated.

PMID- 29348165
TI  - IFCC Working Group Recommendations for Assessing Commutability Part 2: Using the
      Difference in Bias between a Reference Material and Clinical Samples.
AB  - A process is described to assess the commutability of a reference material (RM)
      intended for use as a calibrator, trueness control, or external quality
      assessment sample based on the difference in bias between an RM and clinical
      samples (CSs) measured using 2 different measurement procedures (MPs). This
      difference in bias is compared with a criterion based on a medically relevant
      difference between an RM and CS results to make a conclusion regarding
      commutability. When more than 2 MPs are included, the commutability is assessed
      pairwise for all combinations of 2 MPs. This approach allows the same criterion
      to be used for all combinations of MPs included in the assessment. The assessment
      is based on an error model that allows estimation of various random and
      systematic sources of error, including those from sample-specific effects of
      interfering substances. An advantage of this approach is that the difference in
      bias between an RM and the average bias of CSs at the concentration (i.e., amount
      of substance present or quantity value) of the RM is determined and its
      uncertainty estimated. An RM is considered fit for purpose for those MPs for
      which commutability is demonstrated.

PMID- 29348166
TI  - Clinical Evaluation of a Blood Assay to Diagnose Paucibacillary Tuberculosis via
      Bacterial Antigens.
AB  - BACKGROUND: The diagnosis of active tuberculosis (TB) cases primarily relies on
      methods that detect Mycobacterium tuberculosis (Mtb) bacilli or their DNA in
      patient samples (e.g., mycobacterial culture and Xpert MTB/RIF assays), but these
      tests have low clinical sensitivity for patients with paucibacillary TB disease.
      Our goal was to evaluate the clinical performance of a newly developed assay that
      can rapidly diagnose active TB cases by direct detection of Mtb-derived antigens
      in patients' blood samples. METHODS: Nanoparticle (NanoDisk)-enriched peptides
      derived from the Mtb virulence factors CFP-10 (10-kDa culture factor protein) and
      ESAT-6 (6-kDa early secretory antigenic target) were analyzed by high-throughput
      mass spectrometry (MS). Serum from 294 prospectively enrolled Chinese adults were
      analyzed with this NanoDisk-MS method to evaluate the performance of direct serum
      Mtb antigen measurement as a means for rapid diagnosis of active TB cases.
      RESULTS: NanoDisk-MS diagnosed 174 (88.3%) of the study's TB cases, with 95.8%
      clinical specificity, and with 91.6% and 85.3% clinical sensitivity for culture
      positive and culture-negative TB cases, respectively. NanoDisk-MS also exhibited
      88% clinical sensitivity for pulmonary and 90% for extrapulmonary TB, exceeding
      the diagnostic performance of mycobacterial culture for these cases. CONCLUSIONS:
      Direct detection and quantification of serum Mtb antigens by NanoDisk-MS can
      rapidly and accurately diagnose active TB in adults, independent of disease site
      or culture status, and outperform Mycobacterium-based TB diagnostics.

PMID- 29348167
TI  - Thiosulfate sulfurtransferase-like domain-containing 1 protein interacts with
      thioredoxin.
AB  - Rhodanese domains are structural modules present in the sulfurtransferase
      superfamily. These domains can exist as single units, in tandem repeats, or fused
      to domains with other activities. Despite their prevalence across species, the
      specific physiological roles of most sulfurtransferases are not known. Mammalian
      rhodanese and mercaptopyruvate sulfurtransferase are perhaps the best-studied
      members of this protein superfamily and are involved in hydrogen sulfide
      metabolism. The relatively unstudied human thiosulfate sulfurtransferase-like
      domain-containing 1 (TSTD1) protein, a single-domain cytoplasmic
      sulfurtransferase, was also postulated to play a role in the sulfide oxidation
      pathway using thiosulfate to form glutathione persulfide, for subsequent
      processing in the mitochondrial matrix. Prior kinetic analysis of TSTD1 was
      performed at pH 9.2, raising questions about relevance and the proposed model for
      TSTD1 function. In this study, we report a 1.04 A resolution crystal structure of
      human TSTD1, which displays an exposed active site that is distinct from that of
      rhodanese and mercaptopyruvate sulfurtransferase. Kinetic studies with a
      combination of sulfur donors and acceptors reveal that TSTD1 exhibits a low Km
      for thioredoxin as a sulfane sulfur acceptor and that it utilizes thiosulfate
      inefficiently as a sulfur donor. The active site exposure and its interaction
      with thioredoxin suggest that TSTD1 might play a role in sulfide-based signaling.
      The apical localization of TSTD1 in human colonic crypts, which interfaces with
      sulfide-releasing microbes, and the overexpression of TSTD1 in colon cancer
      provide potentially intriguing clues as to its role in sulfide metabolism.

PMID- 29348168
TI  - The phospholipid-repair system LplT/Aas in Gram-negative bacteria protects the
      bacterial membrane envelope from host phospholipase A2 attack.
AB  - Secretory phospholipases A2 (sPLA2s) are potent components of mammalian innate
      immunity antibacterial mechanisms. sPLA2 enzymes attack bacteria by hydrolyzing
      bacterial membrane phospholipids, causing membrane disorganization and cell
      lysis. However, most Gram-negative bacteria are naturally resistant to sPLA2 Here
      we report a novel resistance mechanism to mammalian sPLA2 in Escherichia coli,
      mediated by a phospholipid repair system consisting of the lysophospholipid
      transporter LplT and the acyltransferase Aas in the cytoplasmic membrane.
      Mutation of the lplT or aas gene abolished bacterial lysophospholipid acylation
      activity and drastically increased bacterial susceptibility to the combined
      actions of inflammatory fluid components and sPLA2, resulting in bulk
      phospholipid degradation and loss of colony-forming ability. sPLA2-mediated
      hydrolysis of the three major bacterial phospholipids exhibited distinctive
      kinetics and deacylation of cardiolipin to its monoacyl-derivative closely
      paralleled bacterial death. Characterization of the membrane envelope in lplT- or
      aas-knockout mutant bacteria revealed reduced membrane packing and disruption of
      lipid asymmetry with more phosphatidylethanolamine present in the outer leaflet
      of the outer membrane. Moreover, modest accumulation of lysophospholipids in
      these mutant bacteria destabilized the inner membrane and rendered outer membrane
      depleted spheroplasts much more sensitive to sPLA2 These findings indicated that
      LplT/Aas inactivation perturbs both the outer and inner membranes by bypassing
      bacterial membrane maintenance mechanisms to trigger specific interfacial
      activation of sPLA2 We conclude that the LplT/Aas system is important for
      maintaining the integrity of the membrane envelope in Gram-negative bacteria. Our
      insights may help inform new therapeutic strategies to enhance host sPLA2
      antimicrobial activity.

PMID- 29348169
TI  - Lipid-mediated signals that regulate mitochondrial biology.
AB  - For decades, lipids were assumed to fulfill roles only in energy storage and
      membrane structure. Recent studies have discovered critical roles for
      phospholipids, sphingolipids, and sterols in many cellular pathways, including
      cell signaling and transcriptional regulation. Frequently, lipids from these
      various classes work together to achieve defined cellular outcomes. Specific
      mitochondrial lipids are critical for proper assembly of the electron transport
      chain complexes and for effective responses to mitochondrial damage, including
      maintenance of mitochondrial protein homeostasis, regulation of mitophagy, and
      induction of apoptosis. In this Minireview, we will primarily focus on
      mitochondrial lipid signaling mediated by lipid-protein interactions.

PMID- 29348170
TI  - CRISPR RNA and anti-CRISPR protein binding to the Xanthomonas albilineans Csy1
      Csy2 heterodimer in the type I-F CRISPR-Cas system.
AB  - Clustered regularly interspaced short palindromic repeats (CRISPRs) and CRISPR
      associated (Cas) proteins provide microbial adaptive immunity against
      bacteriophages. In type I-F CRISPR-Cas systems, multiple Cas proteins (Csy1-4)
      compose a surveillance complex (Csy complex) with CRISPR RNA (crRNA) for target
      recognition. Here, we report the biochemical characterization of the Csy1-Csy2
      subcomplex from Xanthomonas albilineans, including the analysis of its
      interaction with crRNA and AcrF2, an anti-CRISPR (Acr) protein from a phage that
      infects Pseudomonas aeruginosa The X. albilineans Csy1 and Csy2 proteins (XaCsy1
      and XaCsy2, respectively) formed a stable heterodimeric complex that specifically
      bound the 8-nucleotide (nt) 5'-handle of the crRNA. In contrast, the XaCsy1
      XaCsy2 heterodimer exhibited reduced affinity for the 28-nt X. albilineans CRISPR
      repeat RNA containing the 5'-handle sequence. Chromatographic and calorimetric
      analyses revealed tight binding between the Acr protein from the P. aeruginosa
      phage and the heterodimeric subunit of the X. albilineans Csy complex, suggesting
      that AcrF2 recognizes conserved features of Csy1-Csy2 heterodimers. We found that
      neither XaCsy1 nor XaCsy2 alone forms a stable complex with AcrF2 and the 5'
      handle RNA, indicating that XaCsy1-XaCsy2 heterodimerization is required for
      binding them. We also solved the crystal structure of AcrF2 to a resolution of
      1.34 A, enabling a more detailed structural analysis of the residues involved in
      the interactions with the Csy1-Csy2 heterodimer. Our results provide information
      about the order of events during the formation of the multisubunit crRNA-guided
      surveillance complex and suggest that the Acr protein inactivating type I-F
      CRISPR-Cas systems has broad specificity.

PMID- 29348171
TI  - A cationic, C-terminal patch and structural rearrangements in Ebola virus matrix
      VP40 protein control its interactions with phosphatidylserine.
AB  - Ebola virus (EBOV) is a filamentous lipid-enveloped virus that causes hemorrhagic
      fever with a high fatality rate. Viral protein 40 (VP40) is the major EBOV matrix
      protein and regulates viral budding from the plasma membrane. VP40 is a
      transformer/morpheein that can structurally rearrange its native homodimer into
      either a hexameric filament that facilitates viral budding or an RNA-binding
      octameric ring that regulates viral transcription. VP40 associates with plasma
      membrane lipids such as phosphatidylserine (PS), and this association is critical
      to budding from the host cell. However, it is poorly understood how different
      VP40 structures interact with PS, what essential residues are involved in this
      association, and whether VP40 has true selectivity for PS among different
      glycerophospholipid headgroups. In this study, we used lipid-binding assays, MD
      simulations, and cellular imaging to investigate the molecular basis of VP40-PS
      interactions and to determine whether different VP40 structures (i.e. monomer,
      dimer, and octamer) can interact with PS-containing membranes. Results from
      quantitative analysis indicated that VP40 associates with PS vesicles via a
      cationic patch in the C-terminal domain (Lys224, 225 and Lys274, 275).
      Substitutions of these residues with alanine reduced PS-vesicle binding by >40
      fold and abrogated VP40 localization to the plasma membrane. Dimeric VP40 had 2
      fold greater affinity for PS-containing membranes than the monomer, whereas
      binding of the VP40 octameric ring was reduced by nearly 10-fold. Taken together,
      these results suggest the different VP40 structures known to form in the viral
      life cycle harbor different affinities for PS-containing membranes.

PMID- 29348172
TI  - The alpha-arrestin ARRDC3 suppresses breast carcinoma invasion by regulating G
      protein-coupled receptor lysosomal sorting and signaling.
AB  - Aberrant G protein-coupled receptor (GPCR) expression and activation has been
      linked to tumor initiation, progression, invasion, and metastasis. However,
      compared with other cancer drivers, the exploitation of GPCRs as potential
      therapeutic targets has been largely ignored, despite the fact that GPCRs are
      highly druggable. Therefore, to advance the potential status of GPCRs as
      therapeutic targets, it is important to understand how GPCRs function together
      with other cancer drivers during tumor progression. We now report that the alpha
      arrestin domain-containing protein-3 (ARRDC3) acts as a tumor suppressor in part
      by controlling signaling and trafficking of the GPCR, protease-activated receptor
      1 (PAR1). In a series of highly invasive basal-like breast carcinomas, we found
      that expression of ARRDC3 is suppressed whereas PAR1 is aberrantly overexpressed
      because of defective lysosomal sorting that results in persistent signaling.
      Using a lentiviral doxycycline-inducible system, we demonstrate that re
      expression of ARRDC3 in invasive breast carcinoma is sufficient to restore normal
      PAR1 trafficking through the ALG-interacting protein X (ALIX)-dependent lysosomal
      degradative pathway. We also show that ARRDC3 re-expression attenuates PAR1
      stimulated persistent signaling of c-Jun N-terminal kinase (JNK) in invasive
      breast cancer. Remarkably, restoration of ARRDC3 expression significantly reduced
      activated PAR1-induced breast carcinoma invasion, which was also dependent on JNK
      signaling. These findings are the first to identify a critical link between the
      tumor suppressor ARRDC3 and regulation of GPCR trafficking and signaling in
      breast cancer.

PMID- 29348173
TI  - Methanobactins: Maintaining copper homeostasis in methanotrophs and beyond.
AB  - Methanobactins (Mbns) are ribosomally produced, post-translationally modified
      natural products that bind copper with high affinity and specificity. Originally
      identified in methanotrophic bacteria, which have a high need for copper, operons
      encoding these compounds have also been found in many non-methanotrophic
      bacteria. The proteins responsible for Mbn biosynthesis include several novel
      enzymes. Mbn transport involves export through a multidrug efflux pump and re
      internalization via a TonB-dependent transporter. Release of copper from Mbn and
      the molecular basis for copper regulation of Mbn production remain to be
      elucidated. Future work is likely to result in the identification of new
      enzymatic chemistry, opportunities for bioengineering and drug targeting of
      copper metabolism, and an expanded understanding of microbial metal homeostasis.

PMID- 29348175
TI  - Glucose regulates MafA transcription factor abundance and insulin gene expression
      by inhibiting AMP-activated protein kinase in pancreatic beta-cells.
AB  - Insulin mRNA expression in pancreatic islet beta-cells is up-regulated by
      extracellular glucose concentration, but the underlying mechanism remains
      incompletely understood. MafA is a transcriptional activator specifically
      enriched in beta-cells that binds to the insulin gene promoter. Its expression is
      transcriptionally and posttranscriptionally regulated by glucose. Moreover, AMP
      activated protein kinase (AMPK), a regulator of cellular energy homeostasis, is
      inhibited by high glucose, and this inhibition is essential for the up-regulation
      of insulin gene expression and glucose-stimulated insulin secretion (GSIS). Here
      we mutagenized the insulin promoter and found that the MafA-binding element
      C1/RIPE3b is required for glucose- or AMPK-induced alterations in insulin gene
      promoter activity. Under high-glucose conditions, pharmacological activation of
      AMPK in isolated mouse islets or MIN6 cells by metformin or 5-aminoimidazole-4
      carboxamide riboside decreased MafA protein levels and mRNA expression of insulin
      and GSIS-related genes (i.e. glut2 and sur1). Overexpression of constitutively
      active AMPK also reduced MafA and insulin expression. Conversely, pharmacological
      AMPK inhibition by dorsomorphin (compound C) or expression of a dominant-negative
      form of AMPK increased MafA and insulin expression under low-glucose conditions.
      However, AMPK activation or inhibition did not change the expression levels of
      the beta-cell-enriched transcription factors Pdx1 and Beta2/NeuroD1. AMPK
      activation accelerated MafA protein degradation, which is not dependent on the
      proteasome. We also noted that MafA overexpression prevents metformin-induced
      decreases in insulin and GSIS-related gene expression. These findings indicate
      that high glucose concentrations inhibit AMPK, thereby increasing MafA protein
      levels and activating the insulin promoter.

PMID- 29348174
TI  - Oligomer formation and G-quadruplex binding by purified murine Rif1 protein, a
      key organizer of higher-order chromatin architecture.
AB  - Rap1-interacting protein 1 (Rif1) regulates telomere length in budding yeast. We
      previously reported that, in metazoans and fission yeast, Rif1 also plays pivotal
      roles in controlling genome-wide DNA replication timing. We proposed that Rif1
      may assemble chromatin compartments that contain specific replication-timing
      domains by promoting chromatin loop formation. Rif1 also is involved in DNA
      lesion repair, restart after replication fork collapse, anti-apoptosis
      activities, replicative senescence, and transcriptional regulation. Although
      multiple physiological functions of Rif1 have been characterized, biochemical and
      structural information on mammalian Rif1 is limited, mainly because of
      difficulties in purifying the full-length protein. Here, we expressed and
      purified the 2418-amino-acid-long, full-length murine Rif1 as well as its
      partially truncated variants in human 293T cells. Hydrodynamic analyses indicated
      that Rif1 forms elongated or extended homo-oligomers in solution, consistent with
      the presence of a HEAT-type helical repeat segment known to adopt an elongated
      shape. We also observed that the purified murine Rif1 bound G-quadruplex (G4) DNA
      with high specificity and affinity, as was previously shown for Rif1 from fission
      yeast. Both the N-terminal (HEAT-repeat) and C-terminal segments were involved in
      oligomer formation and specifically bound G4 DNA, and the central intrinsically
      disordered polypeptide segment increased the affinity for G4. Of note, pulldown
      assays revealed that Rif1 simultaneously binds multiple G4 molecules. Our
      findings support a model in which Rif1 modulates chromatin loop structures
      through binding to multiple G4 assemblies and by holding chromatin fibers
      together.

PMID- 29348177
TI  - Dasatinib increases endothelial permeability leading to pleural effusion.
AB  - Pleural effusion is a frequent side-effect of dasatinib, a second-generation
      tyrosine kinase inhibitor used in the treatment of chronic myelogenous leukaemia.
      However, the underlying mechanisms remain unknown. We hypothesised that dasatinib
      alters endothelial integrity, resulting in increased pulmonary vascular
      endothelial permeability and pleural effusion.To test this, we established the
      first animal model of dasatinib-related pleural effusion, by treating rats with a
      daily regimen of high doses of dasatinib (10 mg.kg-1.day-1 for 8 weeks).Pleural
      ultrasonography revealed that rats chronically treated with dasatinib developed
      pleural effusion after 5 weeks. Consistent with these in vivo observations,
      dasatinib led to a rapid and reversible increase in paracellular permeability of
      human pulmonary endothelial cell monolayers as reflected by increased
      macromolecule passage, loss of vascular endothelial cadherin and zonula occludens
      1 from cell-cell junctions, and the development of actin stress fibres. These
      results were replicated using human umbilical vein endothelial cells and
      confirmed by decreased endothelial resistance. Interestingly, we demonstrated
      that this increased endothelial permeability is a reactive oxygen species (ROS)
      dependent mechanism in vitro and in vivo using a cotreatment with an antioxidant
      agent, N-acetylcysteine.This study shows that dasatinib alters pulmonary
      endothelial permeability in a ROS-dependent manner in vitro and in vivo leading
      to pleural effusion.

PMID- 29348176
TI  - Contribution of the tRNAIle 4317A->G mutation to the phenotypic manifestation of
      the deafness-associated mitochondrial 12S rRNA 1555A->G mutation.
AB  - The 1555A->G mutation in mitochondrial 12S rRNA has been associated with
      aminoglycoside-induced and non-syndromic deafness in many individuals worldwide.
      Mitochondrial genetic modifiers are proposed to influence the phenotypic
      expression of m.1555A->G mutation. Here, we report that a deafness-susceptibility
      allele (m.4317A->G) in the tRNAIle gene modulates the phenotype expression of
      m.1555A->G mutation. Strikingly, a large Han Chinese pedigree carrying both
      m.4317A->G and m.1555A->G mutations exhibited much higher penetrance of deafness
      than those carrying only the m.1555A->G mutation. The m.4317A->G mutation
      affected a highly conserved adenine at position 59 in the T-loop of tRNAIle We
      therefore hypothesized that the m.4317A->G mutation alters both structure and
      function of tRNAIle Using lymphoblastoid cell lines derived from members of
      Chinese families (three carrying both m.1555A->G and m.4317A->G mutations, three
      harboring only m.1555A->G mutation, and three controls lacking these mutations),
      we found that the cell lines bearing both m.4317A->G and m.1555A->G mutations
      exhibited more severe mitochondrial dysfunctions than those carrying only the
      m.1555A->G mutation. We also found that the m.4317A->G mutation perturbed the
      conformation, stability, and aminoacylation efficiency of tRNAIle These m.4317A
      >G mutation-induced alterations in tRNAIle structure and function aggravated the
      defective mitochondrial translation and respiratory phenotypes associated with
      the m.1555A->G mutation. Furthermore, mutant cell lines bearing both m.4317A->G
      and m.1555A->G mutations exhibited greater reductions in the mitochondrial ATP
      levels and membrane potentials and increasing production of reactive oxygen
      species than those carrying only the m.1555A->G mutation. Our findings provide
      new insights into the pathophysiology of maternally inherited deafness arising
      from the synergy between mitochondrial 12S rRNA and tRNA mutations.

PMID- 29348178
TI  - A scoring system to predict the elevation of mean pulmonary arterial pressure in
      idiopathic pulmonary fibrosis.
AB  - Elevated mean pulmonary arterial pressure (MPAP; >=21 mmHg) is sometimes seen in
      patients with idiopathic pulmonary fibrosis (IPF) and has an adverse impact upon
      survival. Although early diagnosis is crucial, there is no established screening
      tool that uses a combination of noninvasive examinations.We retrospectively
      analysed IPF patients at initial evaluation from April 2007 to July 2015 and,
      using logistic regression analysis, created a screening tool to identify elevated
      MPAP. Internal validation was also assessed for external validity using a
      bootstrap method.Using right-heart catheterisation (RHC), elevation of MPAP was
      determined to be present in 55 out of 273 patients. Multivariate models
      demonstrated that % predicted diffusing capacity of the lung for carbon monoxide
      (DLCO) <50%, ratio of pulmonary artery diameter to aorta diameter (PA/Ao) on
      computed tomography (CT) >=0.9 and arterial oxygen tension (PaO2 ) <80 Torr were
      independent predictors. When we assigned a single point to each variable, the
      prevalence of elevation of MPAP with a score of zero, one, two or three points
      was 6.7%, 16.0%, 29.1% and 65.4%, respectively. The area under curve (AUC) for
      the receiver operating characteristic (ROC) curve was good at 0.757 (95% CI 0.682
      0.833).A simple clinical scoring system consisting of % predicted DLCO, PA/Ao
      ratio on CT and PaO2 can easily predict elevation of MPAP in patients with IPF.

PMID- 29348179
TI  - Cigarette smoking and response to inhaled corticosteroids in COPD.

PMID- 29348180
TI  - Persistently elevated exhaled nitric oxide fraction is associated with increased
      risk of exacerbation in COPD.
AB  - Preventing the occurrence of acute exacerbations of chronic obstructive pulmonary
      disease (AECOPD) is a major therapeutic goal. We hypothesise that persistently
      increased levels of exhaled nitric oxide (FeNO) during follow-up can identify a
      group of COPD patients at higher risk of AECOPD.To test this hypothesis, we
      measured FeNO levels (HypAir FeNO(r), Medisoft; Sorinnes, Belgium) prospectively
      in 226 clinically stable COPD outpatients at recruitment and during follow-up (at
      6 and 12 months). Patients were stratified according to the number of visits with
      FeNO >=20 ppb.FeNO was <20 ppb in all three visits in 44.2% of patients, 29.6% in
      visit 1 and 26.1% in visit 2 or 3. These three groups suffered progressively
      higher AECOPD rates during follow-up (0.67, 0.91 and 1.42, respectively,
      p<0.001). After adjusting for potential confounding variables (log-rank test),
      the hazard ratio for AECOPD was higher in the latter group (1.579 (95% CI 1.049
      2.378), p=0.029). Likewise, time to first moderate and severe AECOPD was shorter
      in these patients. Finally, there was no relationship between FeNO levels and
      circulating eosinophils.Persistent FeNO levels >=20 ppb in clinically stable COPD
      outpatients are associated with a significantly higher risk of AECOPD.

PMID- 29348181
TI  - Intensity of exposure to pulmonary tuberculosis determines risk of tuberculosis
      infection and disease.
AB  - Household contacts of pulmonary tuberculosis (TB) patients are at increased risk
      of TB infection and disease. However, their risk in relation to the intensity of
      exposure remains unknown.We studied smear-positive TB cases and their household
      contacts in Vitoria, Brazil. We collected clinical, demographic and radiographic
      information from TB cases, and obtained tuberculin skin test (TST) and
      QuantiFERON-TB Gold (QFT) results from household contacts. We measured intensity
      of exposure using a proximity score and sleep location in relation to the TB
      index case and defined infection by TST >=10 mm or QFT >=0.35 UI.mL-1 We
      ascertained secondary TB cases by reviewing local and nationwide case
      registries.We included 160 TB index cases and 894 household contacts. 464 (65%)
      had TB infection and 23 (2.6%) developed TB disease. Risk of TB infection and
      disease increased with more intense exposures. In an adjusted analysis, the
      proximity score was associated with TB disease (OR 1.61, 95% CI 1.25-2.08;
      p<0.000); however, its diagnostic performance was only moderate.Intensity of
      exposure increased risk of TB infection and disease among household contacts;
      however, its diagnostic performance was still suboptimal. A biomarker to target
      preventive therapy is urgently needed in this at-risk population.

PMID- 29348182
TI  - Trends in mortality from idiopathic pulmonary fibrosis in the European Union: an
      observational study of the WHO mortality database from 2001-2013.
AB  - Idiopathic pulmonary fibrosis (IPF) is the most common of the idiopathic
      interstitial pneumonias and is characterised by progressive accumulation of scar
      tissue in the lungs. The objective of this study was to describe the current
      mortality rates due to IPF in Europe, based on the World Health Organization
      (WHO) mortality database.We used country-level data for IPF mortality, identified
      in the WHO mortality database using International Classification of Diseases 10th
      Edition (ICD-10) codes, for the period 2001-2013. Joinpoint analysis was
      performed to describe trends throughout the observation period.The median
      mortality was 3.75 per 100 000 (interquartile range (IQR) 1.37-5.30) and 1.50 per
      100 000 (IQR 0.65-2.02) for males and females, respectively. IPF mortality
      increased in the majority of the European Union (EU) countries with the
      exceptions of Denmark, Croatia, Austria and Romania. There was a significant
      disparity in rates across Europe, in the range 0.41-12.1 per 100 000 for men and
      0.24-5.63 per 100 000 for women. The most notable increases were observed in the
      United Kingdom and Finland. Rates were also substantially higher in males, with
      sex disparity increasing across the period.The reported IPF mortality appears to
      be increasing across the EU; however, there is substantial variation in mortality
      trends and overall reported mortality rates between countries.

PMID- 29348183
TI  - Neurophysiological mechanisms of exertional dyspnoea in fibrotic interstitial
      lung disease.
AB  - Our understanding of the mechanisms of dyspnoea in fibrotic interstitial lung
      disease (ILD) is incomplete. The aims of this study were two-fold: 1) to
      determine whether dyspnoea intensity is better predicted by neural respiratory
      drive (NRD) or neuromechanical uncoupling (NMU) of the respiratory system in
      fibrotic ILD, and 2) to examine the effect of breathing 60% oxygen on NRD, NMU
      and dyspnoea ratings.Fourteen patients with fibrotic ILD were included. Visit 1
      comprised a familiarisation incremental cycle exercise test, Visit 2 comprised a
      normoxic incremental cycling test to address Aim 1, and Visits 3 and 4 consisted
      of constant-load cycling while breathing room air or 60% oxygen to address Aim 2.
      Diaphragmatic electromyography (EMGdi) was used as a surrogate of NRD. NMU was
      calculated as the ratio between EMGdi (%max) and tidal volume (%vital
      capacity).On adjusted analysis, NMU and its constituents were all significantly
      associated with dyspnoea ratings during incremental cycling, with EMGdi having
      the strongest correlation. The between-treatment change in dyspnoea ratings
      during constant load cycling was only correlated with change in exercise
      endurance time and NMU.Dyspnoea more strongly reflected the level of EMGdi than
      NMU in fibrotic ILD. However, the improvement in dyspnoea with 60% oxygen was
      better predicted by improvements in NMU.

PMID- 29348184
TI  - Improved identification of thrombolysis candidates amongst intermediate-risk
      pulmonary embolism patients: implications for future trials.

PMID- 29348185
TI  - Daily home spirometry to detect early steroid treatment effects in newly treated
      pulmonary sarcoidosis.

PMID- 29348186
TI  - Can YKL-40 be used as a biomarker and therapeutic target for adult asthma?

PMID- 29348187
TI  - The increasing mortality of idiopathic pulmonary fibrosis: fact or fallacy?

PMID- 29348188
TI  - The unmet medical need of pulmonary hypertension in idiopathic pulmonary
      fibrosis.

PMID- 29348189
TI  - Cancer Stem Cell Phenotypes in ER+ Breast Cancer Models Are Promoted by
      PELP1/AIB1 Complexes.
AB  - Proline, glutamic acid, leucine-rich protein 1 (PELP1) is overexpressed in
      approximately 80% of invasive breast tumors. PELP1 dynamically shuttles between
      the nucleus and cytoplasm, but is primarily nuclear in normal breast tissue.
      However, altered localization of PELP1 to the cytoplasm is an oncogenic event
      that promotes breast cancer initiation and progression. Herein, interacting
      partners unique to cytoplasmic PELP1 and the mechanisms by which these
      interactions promote oncogenic PELP1 signaling were sought. AIB1 (amplified in
      breast cancer 1; also known as SRC-3 or NCOA3) was identified as a novel binding
      partner of cytoplasmic PELP1 in both estrogen receptor-positive (ER+) and ER
      negative cell lines. Cytoplasmic PELP1 expression elevated basal phosphorylation
      levels (i.e., activation) of AIB1 at Thr24, enhanced ALDH+ tumorsphere formation,
      and upregulated specific target genes independently of hormone stimulation.
      Direct manipulation of AIB1 levels using shRNA abrogated cytoplasmic PELP1
      induced tumorsphere formation and downregulated cytoplasmic PELP1-specific target
      genes. SI-2, an AIB1 inhibitor, limited the PELP1/AIB1 interaction and decreased
      cytoplasmic PELP1-induced tumorsphere formation. Similar results were observed in
      a murine-derived MMTV-AIB1 tumor cell line. Furthermore, in vivo syngeneic tumor
      studies revealed that PELP1 knockdown resulted in increased survival of tumor
      bearing mice as compared with mice injected with control cells.Implications:
      These data demonstrate that cytoplasmic PELP1/AIB1-containing complexes function
      to promote advanced cancer phenotypes, including outgrowth of stem-like cells,
      associated with estrogen-independent breast cancer progression. Mol Cancer Res;
      16(4); 707-19. (c)2018 AACR.

PMID- 29348192
TI  - Differential Contributions of Nucleus Accumbens Subregions to Cue-Guided
      Risk/Reward Decision Making and Implementation of Conditional Rules.
AB  - The nucleus accumbens (NAc) is a key node within corticolimbic circuitry for
      guiding action selection and cost/benefit decision making in situations involving
      reward uncertainty. Preclinical studies have typically assessed risk/reward
      decision making using assays where decisions are guided by internally generated
      representations of choice-outcome contingencies. Yet, real-life decisions are
      often influenced by external stimuli that inform about likelihoods of obtaining
      rewards. How different subregions of the NAc mediate decision making in such
      situations is unclear. Here, we used a novel assay colloquially termed the
      "Blackjack" task that models these types of situations. Male Long-Evans rats were
      trained to choose between one lever that always delivered a one-pellet reward and
      another that delivered four pellets with different probabilities [either 50%
      (good-odds) or 12.5% (poor-odds)], which were signaled by one of two auditory
      cues. Under control conditions, rats selected the large/risky option more often
      on good-odds versus poor-odds trials. Inactivation of the NAc core caused
      indiscriminate choice patterns. In contrast, NAc shell inactivation increased
      risky choice, more prominently on poor-odds trials. Additional experiments
      revealed that both subregions contribute to auditory conditional discrimination.
      NAc core or shell inactivation reduced Pavlovian approach elicited by an auditory
      CS+, yet shell inactivation also increased responding during presentation of a CS
      . These data highlight distinct contributions for NAc subregions in decision
      making and reward seeking guided by discriminative stimuli. The core is crucial
      for implementation of conditional rules, whereas the shell refines reward seeking
      by mitigating the allure of larger, unlikely rewards and reducing expression of
      inappropriate or non-rewarded actions.SIGNIFICANCE STATEMENT Using external cues
      to guide decision making is crucial for adaptive behavior. Deficits in cue-guided
      behavior have been associated with neuropsychiatric disorders, such as attention
      deficit hyperactivity disorder and schizophrenia, which in turn has been linked
      to aberrant processing in the nucleus accumbens. However, many preclinical
      studies have often assessed risk/reward decision making in the absence of
      explicit cues. The current study fills that gap by using a novel task that allows
      for the assessment of cue-guided risk/reward decision making in rodents. Our
      findings identified distinct yet complementary roles for the medial versus
      lateral portions of this nucleus that provide a broader understanding of the
      differential contributions it makes to decision making and reward seeking guided
      by discriminative stimuli.

PMID- 29348190
TI  - Pronounced Hyperactivity, Cognitive Dysfunctions, and BDNF Dysregulation in
      Dopamine Transporter Knock-out Rats.
AB  - Dopamine (DA) controls many vital physiological functions and is critically
      involved in several neuropsychiatric disorders such as schizophrenia and
      attention deficit hyperactivity disorder. The major function of the plasma
      membrane dopamine transporter (DAT) is the rapid uptake of released DA into
      presynaptic nerve terminals leading to control of both the extracellular levels
      of DA and the intracellular stores of DA. Here, we present a newly developed
      strain of rats in which the gene encoding DAT knockout Rats (DAT-KO) has been
      disrupted by using zinc finger nuclease technology. Male and female DAT-KO rats
      develop normally but weigh less than heterozygote and wild-type rats and
      demonstrate pronounced spontaneous locomotor hyperactivity. While striatal
      extracellular DA lifetime and concentrations are significantly increased, the
      total tissue content of DA is markedly decreased demonstrating the key role of
      DAT in the control of DA neurotransmission. Hyperactivity of DAT-KO rats can be
      counteracted by amphetamine, methylphenidate, the partial Trace Amine-Associated
      Receptor 1 (TAAR1) agonist RO5203648 ((S)-4-(3,4-Dichloro-phenyl)-4,5-dihydro
      oxazol-2-ylamine) and haloperidol. DAT-KO rats also demonstrate a deficit in
      working memory and sensorimotor gating tests, less propensity to develop
      obsessive behaviors and show strong dysregulation in frontostriatal BDNF
      function. DAT-KO rats could provide a novel translational model for human
      diseases involving aberrant DA function and/or mutations affecting DAT or related
      regulatory mechanisms.SIGNIFICANCE STATEMENT Here, we present a newly developed
      strain of rats in which the gene encoding the dopamine transporter (DAT) has been
      disrupted (Dopamine Transporter Knockout rats [DAT-KO rats]). DAT-KO rats display
      functional hyperdopaminergia accompanied by pronounced spontaneous locomotor
      hyperactivity. Hyperactivity of DAT-KO rats can be counteracted by amphetamine,
      methylphenidate, and a few other compounds exerting inhibitory action on dopamine
      dependent hyperactivity. DAT-KO rats also demonstrate cognitive deficits in
      working memory and sensorimotor gating tests, less propensity to develop
      compulsive behaviors, and strong dysregulation in frontostriatal BDNF function.
      These observations highlight the key role of DAT in the control of brain
      dopaminergic transmission. DAT-KO rats could provide a novel translational model
      for human diseases involving aberrant dopamine functions.

PMID- 29348193
TI  - Heartbeat: Computed tomographic coronary angiography in patients with possible
      angina.

PMID- 29348191
TI  - Multimodal Encoding of Novelty, Reward, and Learning in the Primate Nucleus
      Basalis of Meynert.
AB  - Associative learning is crucial for daily function, involving a complex network
      of brain regions. One region, the nucleus basalis of Meynert (NBM), is a highly
      interconnected, largely cholinergic structure implicated in multiple aspects of
      learning. We show that single neurons in the NBM of nonhuman primates (NHPs; n =
      2 males; Macaca mulatta) encode learning a new association through spike rate
      modulation. However, the power of low-frequency local field potential (LFP)
      oscillations decreases in response to novel, not-yet-learned stimuli but then
      increase as learning progresses. Both NBM and the dorsolateral prefrontal cortex
      encode confidence in novel associations by increasing low- and high-frequency LFP
      power in anticipation of expected rewards. Finally, NBM high-frequency power
      dynamics are anticorrelated with spike rate modulations. Therefore, novelty,
      learning, and reward anticipation are separately encoded through differentiable
      NBM signals. By signaling both the need to learn and confidence in newly acquired
      associations, NBM may play a key role in coordinating cortical activity
      throughout the learning process.SIGNIFICANCE STATEMENT Degradation of cells in a
      key brain region, the nucleus basalis of Meynert (NBM), correlates with
      Alzheimer's disease and Parkinson's disease progression. To better understand the
      role of this brain structure in learning and memory, we examined neural activity
      in the NBM in behaving nonhuman primates while they performed a learning and
      memory task. We found that single neurons in NBM encoded both salience and an
      early learning, or cognitive state, whereas populations of neurons in the NBM and
      prefrontal cortex encode learned state and reward anticipation. The NBM may thus
      encode multiple stages of learning. These multimodal signals might be leveraged
      in future studies to develop neural stimulation to facilitate different stages of
      learning and memory.

PMID- 29348194
TI  - Health Care Costs Associated With Incident Complications in Patients With Type 2
      Diabetes in Germany.
AB  - OBJECTIVE: The aim of this study is to provide reliable regression-based
      estimates of costs associated with different type 2 diabetes complications.
      RESEARCH DESIGN AND METHODS: We used nationwide statutory health insurance (SHI)
      data from 316,220 patients with type 2 diabetes. Costs for inpatient and
      outpatient care, pharmaceuticals, rehabilitation, and nonmedical aids and
      appliances were assessed in the years 2013-2015. Quarterly observations are
      available for each year. We estimated costs (in 2015 euro) for complications
      using a generalized estimating equations model with a normal distribution
      adjusted for age, sex, occurrence of different complications, and history of
      complications at baseline, 2012. Two- and threefold interactions were included in
      an extended model. RESULTS: The base case model estimated total costs in the
      quarter of event for the example of a 60- to 69-year-old man as follows: diabetic
      foot ?1,293, amputation ?14,284, retinopathy ?671, blindness ?2,933, nephropathy
      ?3,353, end-stage renal disease (ESRD) ?22,691, nonfatal stroke ?9,769, fatal
      stroke ?11,176, nonfatal myocardial infarction (MI)/cardiac arrest (CA) ?8,035,
      fatal MI/CA ?8,700, nonfatal ischemic heart disease (IHD) ?6,548, fatal IHD
      ?20,942, chronic heart failure ?3,912, and angina pectoris ?2,695. In the
      subsequent quarters, costs ranged from ?681 for retinopathy to ?6,130 for ESRD.
      CONCLUSIONS: Type 2 diabetes complications have a significant impact on total
      health care costs in the SHI system, not only in the quarter of event but also in
      subsequent years. Men and women from different age-groups differ in their costs
      for complications. Our comprehensive estimates may support the parametrization of
      diabetes models and help clinicians and policy makers to quantify the economic
      burden of diabetes complications in the context of new prevention and treatment
      programs.

PMID- 29348195
TI  - Morbidity and Mortality in Small for Gestational Age Infants at 22 to 29 Weeks'
      Gestation.
AB  - OBJECTIVES: To identify the relative risks of mortality and morbidities for small
      for gestational age (SGA) infants in comparison with non-SGA infants born at 22
      to 29 weeks' gestation. METHODS: Data were collected (2006-2014) on 156 587
      infants from 852 US centers participating in the Vermont Oxford Network. We
      defined SGA as sex-specific birth weight <10th centile for gestational age (GA)
      in days. Binomial generalized additive models with a thin plate spline term on GA
      by SGA were used to calculate the adjusted relative risks and 95% confidence
      intervals for outcomes by GA. RESULTS: Compared with non-SGA infants, the risk of
      patent ductus arteriosus decreased for SGA infants in early GA and then increased
      in later GA. SGA infants were also at increased risks of mortality, respiratory
      distress syndrome, necrotizing enterocolitis, late-onset sepsis, severe
      retinopathy of prematurity, and chronic lung disease. These risks of adverse
      outcomes, however, were not homogeneous across the GA range. Early-onset sepsis
      was not different between the 2 groups for the majority of GAs, although severe
      intraventricular hemorrhage was decreased among SGA infants for only gestational
      week 24 through week 25. CONCLUSIONS: SGA was associated with additional risks to
      mortality and morbidities, but the risks differed across the GA range.

PMID- 29348196
TI  - Placental Findings and Effect of Prophylactic Hydrocortisone in Extremely Preterm
      Infants.
AB  - OBJECTIVES: To investigate the relationship between histologic findings of the
      placenta and response to early postnatal hydrocortisone treatment used to prevent
      bronchopulmonary dysplasia (BPD) in extremely preterm infants. METHODS: In an
      exploratory analysis of the Early Low-Dose Hydrocortisone to Improve Survival
      Without Bronchopulmonary Dysplasia in Extremely Preterm Infants (PREMILOC) trial,
      detailed placental analyses were performed on the basis of standardized
      macroscopic and histologic examinations. Placental histology, categorized into 3
      groups, was correlated to neonatal outcomes and response to hydrocortisone
      treatment. RESULTS: Of 523 randomly assigned patients, 457 placentas were
      analyzed. In total, 125 out of 457 (27%) placentas were classified as normal, 236
      out of 457 (52%) placentas were classified as inflammatory, and 96 out of 457
      (21%) placentas were classified as vascular. Placental inflammation was
      associated with a significant, increased rate of BPD-free survival at 36 weeks'
      postmenstrual age, independent of gestational age, treatment group, and sex
      (adjusted odds ratio: 1.72, 95% confidence interval [CI]: 1.05 to 2.82, P = .03).
      Regarding the response to treatment, the strongest benefit of hydrocortisone
      compared with placebo was found in infants born after placental vascular disease,
      with significantly more patients extubated at day 10 (risk difference: 0.32, 95%
      CI: 0.08 to 0.56, P = .004) and similar positive direction on survival without
      BPD (risk difference: 0.23, 95% CI: 0.00 to 0.46, P = .06). Adjusted to
      gestational age and treatment groups, placental inflammation was associated with
      significantly fewer patent ductus arteriosus ligation (adjusted hazard ratio:
      0.58, 95% CI: 0.36 to 0.95, P = .03). Placental histology was not found to be
      associated with other adverse events related to preterm birth. CONCLUSIONS: With
      these findings, we confirm that early low-dose hydrocortisone confers benefits in
      extremely preterm infants overall and we suggest there is a higher treatment
      effect in those born after placental vascular disease.

PMID- 29348197
TI  - Tackling hearing loss to improve the care of older adults.

PMID- 29348198
TI  - Interleukin-10 stiffens the heart.
AB  - Cardiac-resident macrophages are a diverse population of cells that have a
      critical role in the pathogenesis of heart failure. A new understanding of
      communication between macrophages and cardiac fibroblasts could lead to novel
      therapeutic strategies for heart failure with preserved ejection function.

PMID- 29348199
TI  - Origins of low-symmetry phases in asymmetric diblock copolymer melts.
AB  - Cooling disordered compositionally asymmetric diblock copolymers leads to the
      formation of nearly spherical particles, each containing hundreds of molecules,
      which crystallize upon cooling below the order-disorder transition temperature
      (TODT). Self-consistent field theory (SCFT) reveals that dispersity in the block
      degrees of polymerization stabilizes various Frank-Kasper phases, including the
      C14 and C15 Laves phases, which have been accessed experimentally in low-molar
      mass poly(isoprene)-b-poly(lactide) (PI-PLA) diblock copolymers using thermal
      processing strategies. Heating and cooling a specimen containing 15% PLA above
      and below the TODT from the body-centered cubic (BCC) or C14 states regenerates
      the same crystalline order established at lower temperatures. This memory effect
      is also demonstrated with a specimen containing 20% PLA, which recrystallizes to
      either C15 or hexagonally ordered cylinders (HEXC) upon heating and cooling. The
      process-path-dependent formation of crystalline order shapes the number of
      particles per unit volume, n/V, which is retained in the highly structured
      disordered liquid as revealed by small-angle X-ray scattering (SAXS) experiments.
      We hypothesize that symmetry breaking during crystallization is governed by the
      particle number density imprinted in the liquid during ordering at lower
      temperature, and this metastable liquid is kinetically constrained from
      equilibrating due to prohibitively large free energy barriers for micelle fusion
      and fission. Ordering at fixed n/V is enabled by facile chain exchange, which
      redistributes mass as required to meet the multiple particle sizes and packing
      associated with specific low-symmetry Frank-Kasper phases. This discovery exposes
      universal concepts related to order and disorder in self-assembled soft
      materials.

PMID- 29348200
TI  - Active learning machine learns to create new quantum experiments.
AB  - How useful can machine learning be in a quantum laboratory? Here we raise the
      question of the potential of intelligent machines in the context of scientific
      research. A major motivation for the present work is the unknown reachability of
      various entanglement classes in quantum experiments. We investigate this question
      by using the projective simulation model, a physics-oriented approach to
      artificial intelligence. In our approach, the projective simulation system is
      challenged to design complex photonic quantum experiments that produce high
      dimensional entangled multiphoton states, which are of high interest in modern
      quantum experiments. The artificial intelligence system learns to create a
      variety of entangled states and improves the efficiency of their realization. In
      the process, the system autonomously (re)discovers experimental techniques which
      are only now becoming standard in modern quantum optical experiments-a trait
      which was not explicitly demanded from the system but emerged through the process
      of learning. Such features highlight the possibility that machines could have a
      significantly more creative role in future research.

PMID- 29348201
TI  - Solution structure of sperm lysin yields novel insights into molecular dynamics
      of rapid protein evolution.
AB  - Protein evolution is driven by the sum of different physiochemical and genetic
      processes that usually results in strong purifying selection to maintain
      biochemical functions. However, proteins that are part of systems under arms race
      dynamics often evolve at unparalleled rates that can produce atypical biochemical
      properties. In the marine mollusk abalone, lysin and vitelline envelope receptor
      for lysin (VERL) are a pair of rapidly coevolving proteins that are essential for
      species-specific interactions between sperm and egg. Despite extensive
      biochemical characterization of lysin-including crystal structures of multiple
      orthologs-it was unclear how sites under positive selection may facilitate
      recognition of VERL. Using a combination of targeted mutagenesis and
      multidimensional NMR, we present a high-definition solution structure of sperm
      lysin from red abalone (Haliotis rufescens). Unapparent from the crystallography
      data, multiple NMR-based analyses conducted in solution reveal clustering of the
      N and C termini to form a nexus of 13 positively selected sites that constitute a
      VERL binding interface. Evolutionary rate was found to be a significant predictor
      of backbone flexibility, which may be critical for lysin bioactivity and/or
      accelerated evolution. Flexible, rapidly evolving segments that constitute the
      VERL binding interface were also the most distorted regions of the crystal
      structure relative to what was observed in solution. While lysin has been the
      subject of extensive biochemical and evolutionary analyses for more than 30
      years, this study highlights the enhanced insights gained from applying NMR
      approaches to rapidly evolving proteins.

PMID- 29348202
TI  - Molecular characterization of latent GDF8 reveals mechanisms of activation.
AB  - Growth/differentiation factor 8 (GDF8), or myostatin, negatively regulates muscle
      mass. GDF8 is held in a latent state through interactions with its N-terminal
      prodomain, much like TGF-beta. Using a combination of small-angle X-ray
      scattering and mutagenesis, we characterized the interactions of GDF8 with its
      prodomain. Our results show that the prodomain:GDF8 complex can exist in a fully
      latent state and an activated or "triggered" state where the prodomain remains in
      complex with the mature domain. However, these states are not reversible,
      indicating the latent GDF8 is "spring-loaded." Structural analysis shows that the
      prodomain:GDF8 complex adopts an "open" configuration, distinct from the latency
      state of TGF-beta and more similar to the open state of Activin A and BMP9
      (nonlatent complexes). We determined that GDF8 maintains similar features for
      latency, including the alpha-1 helix and fastener elements, and identified a
      series of mutations in the prodomain of GDF8 that alleviate latency, including
      I56E, which does not require activation by the protease Tolloid. In vivo, active
      GDF8 variants were potent negative regulators of muscle mass, compared with WT
      GDF8. Collectively, these results help characterize the latency and activation
      mechanisms of GDF8.

PMID- 29348203
TI  - Infectious virus in exhaled breath of symptomatic seasonal influenza cases from a
      college community.
AB  - Little is known about the amount and infectiousness of influenza virus shed into
      exhaled breath. This contributes to uncertainty about the importance of airborne
      influenza transmission. We screened 355 symptomatic volunteers with acute
      respiratory illness and report 142 cases with confirmed influenza infection who
      provided 218 paired nasopharyngeal (NP) and 30-minute breath samples (coarse >5
      um and fine <=5-um fractions) on days 1-3 after symptom onset. We assessed viral
      RNA copy number for all samples and cultured NP swabs and fine aerosols. We
      recovered infectious virus from 52 (39%) of the fine aerosols and 150 (89%) of
      the NP swabs with valid cultures. The geometric mean RNA copy numbers were 3.8 *
      104/30-minutes fine-, 1.2 * 104/30-minutes coarse-aerosol sample, and 8.2 * 108
      per NP swab. Fine- and coarse-aerosol viral RNA were positively associated with
      body mass index and number of coughs and negatively associated with increasing
      days since symptom onset in adjusted models. Fine-aerosol viral RNA was also
      positively associated with having influenza vaccination for both the current and
      prior season. NP swab viral RNA was positively associated with upper respiratory
      symptoms and negatively associated with age but was not significantly associated
      with fine- or coarse-aerosol viral RNA or their predictors. Sneezing was rare,
      and sneezing and coughing were not necessary for infectious aerosol generation.
      Our observations suggest that influenza infection in the upper and lower airways
      are compartmentalized and independent.

PMID- 29348204
TI  - Tumor suppressor APC is an attenuator of spindle-pulling forces during C. elegans
      asymmetric cell division.
AB  - The adenomatous polyposis coli (APC) tumor suppressor has dual functions in
      Wnt/beta-catenin signaling and accurate chromosome segregation and is frequently
      mutated in colorectal cancers. Although APC contributes to proper cell division,
      the underlying mechanisms remain poorly understood. Here we show that
      Caenorhabditis elegans APR-1/APC is an attenuator of the pulling forces acting on
      the mitotic spindle. During asymmetric cell division of the C. elegans zygote, a
      LIN-5/NuMA protein complex localizes dynein to the cell cortex to generate
      pulling forces on astral microtubules that position the mitotic spindle. We found
      that APR-1 localizes to the anterior cell cortex in a Par-aPKC polarity-dependent
      manner and suppresses anterior centrosome movements. Our combined cell biological
      and mathematical analyses support the conclusion that cortical APR-1 reduces
      force generation by stabilizing microtubule plus-ends at the cell cortex.
      Furthermore, APR-1 functions in coordination with LIN-5 phosphorylation to
      attenuate spindle-pulling forces. Our results document a physical basis for the
      attenuation of spindle-pulling force, which may be generally used in asymmetric
      cell division and, when disrupted, potentially contributes to division defects in
      cancer.

PMID- 29348205
TI  - Structure of the fission yeast actomyosin ring during constriction.
AB  - Cell division in many eukaryotes is driven by a ring containing actin and myosin.
      While much is known about the main proteins involved, the precise arrangement of
      actin filaments within the contractile machinery, and how force is transmitted to
      the membrane, remains unclear. Here we use cryosectioning and cryofocused ion
      beam milling to gain access to cryopreserved actomyosin rings in
      Schizosaccharomyces pombe for direct 3D imaging by electron cryotomography. Our
      results show that straight, overlapping actin filaments, running nearly parallel
      to each other and to the membrane, form a loose bundle of ~150 nm in diameter
      that "saddles" the inward-bending membrane at the leading edge of the division
      septum. The filaments do not make direct contact with the membrane. Our analysis
      of the actin filaments reveals the variability in filament number, nearest
      neighbor distances between filaments within the bundle, their distance from the
      membrane, and angular distribution with respect to the membrane.

PMID- 29348206
TI  - Rotational 3D printing of damage-tolerant composites with programmable mechanics.
AB  - Natural composites exhibit exceptional mechanical performance that often arises
      from complex fiber arrangements within continuous matrices. Inspired by these
      natural systems, we developed a rotational 3D printing method that enables
      spatially controlled orientation of short fibers in polymer matrices solely by
      varying the nozzle rotation speed relative to the printing speed. Using this
      method, we fabricated carbon fiber-epoxy composites composed of volume elements
      (voxels) with programmably defined fiber arrangements, including adjacent regions
      with orthogonally and helically oriented fibers that lead to nonuniform strain
      and failure as well as those with purely helical fiber orientations akin to
      natural composites that exhibit enhanced damage tolerance. Our approach broadens
      the design, microstructural complexity, and performance space for fiber
      reinforced composites through site-specific optimization of their fiber
      orientation, strain, failure, and damage tolerance.

PMID- 29348207
TI  - QnAs with Frank S. Bates.

PMID- 29348208
TI  - Learning to make external sensory stimulus predictions using internal
      correlations in populations of neurons.
AB  - To compensate for sensory processing delays, the visual system must make
      predictions to ensure timely and appropriate behaviors. Recent work has found
      predictive information about the stimulus in neural populations early in vision
      processing, starting in the retina. However, to utilize this information, cells
      downstream must be able to read out the predictive information from the spiking
      activity of retinal ganglion cells. Here we investigate whether a downstream cell
      could learn efficient encoding of predictive information in its inputs from the
      correlations in the inputs themselves, in the absence of other instructive
      signals. We simulate learning driven by spiking activity recorded in salamander
      retina. We model a downstream cell as a binary neuron receiving a small group of
      weighted inputs and quantify the predictive information between activity in the
      binary neuron and future input. Input weights change according to spike timing
      dependent learning rules during a training period. We characterize the readouts
      learned under spike timing-dependent synaptic update rules, finding that although
      the fixed points of learning dynamics are not associated with absolute optimal
      readouts they convey nearly all of the information conveyed by the optimal
      readout. Moreover, we find that learned perceptrons transmit position and
      velocity information of a moving-bar stimulus nearly as efficiently as optimal
      perceptrons. We conclude that predictive information is, in principle, readable
      from the perspective of downstream neurons in the absence of other inputs. This
      suggests an important role for feedforward prediction in sensory encoding.

PMID- 29348209
TI  - Influence of water and enzyme SpnF on the dynamics and energetics of the
      ambimodal [6+4]/[4+2] cycloaddition.
AB  - SpnF is the first monofunctional Diels-Alder/[6+4]-ase that catalyzes a reaction
      leading to both Diels-Alder and [6+4] adducts through a single transition state.
      The environment-perturbed transition-state sampling method has been developed to
      calculate free energies, kinetic isotope effects, and quasi-classical reaction
      trajectories of enzyme-catalyzed reactions and the uncatalyzed reaction in water.
      Energetics calculated in this way reproduce the experiment and show that the
      normal Diels-Alder transition state is stabilized by H bonds with water
      molecules, while the ambimodal transition state is favored in the enzyme SpnF by
      both intramolecular hydrogen bonding and hydrophobic binding. Molecular dynamics
      simulations show that trajectories passing through the ambimodal transition state
      bifurcate to the [6+4] adduct and the Diels-Alder adduct with a ratio of 1:1 in
      the gas phase, 1:1.6 in water, and 1:11 in the enzyme. This example shows how an
      enzyme acts on a vibrational time scale to steer post-transition state
      trajectories toward the Diels-Alder adduct.

PMID- 29348212
TI  - The 1918 flu, 100 years later.

PMID- 29348213
TI  - News at a glance.

PMID- 29348214
TI  - Newborn exoplanet eyed for moons and rings.

PMID- 29348210
TI  - Toward dynamic structural biology: Two decades of single-molecule Forster
      resonance energy transfer.
AB  - Classical structural biology can only provide static snapshots of
      biomacromolecules. Single-molecule Forster resonance energy transfer (smFRET)
      paved the way for studying dynamics in macromolecular structures under
      biologically relevant conditions. Since its first implementation in 1996, smFRET
      experiments have confirmed previously hypothesized mechanisms and provided new
      insights into many fundamental biological processes, such as DNA maintenance and
      repair, transcription, translation, and membrane transport. We review 22 years of
      contributions of smFRET to our understanding of basic mechanisms in biochemistry,
      molecular biology, and structural biology. Additionally, building on current
      state-of-the-art implementations of smFRET, we highlight possible future
      directions for smFRET in applications such as biosensing, high-throughput
      screening, and molecular diagnostics.

PMID- 29348215
TI  - 'Liquid biopsy' for cancer promises early detection.

PMID- 29348211
TI  - Membrane protein insertion through a mitochondrial beta-barrel gate.
AB  - The biogenesis of mitochondria, chloroplasts, and Gram-negative bacteria requires
      the insertion of beta-barrel proteins into the outer membranes. Homologous Omp85
      proteins are essential for membrane insertion of beta-barrel precursors. It is
      unknown if precursors are threaded through the Omp85-channel interior and exit
      laterally or if they are translocated into the membrane at the Omp85-lipid
      interface. We have mapped the interaction of a precursor in transit with the
      mitochondrial Omp85-channel Sam50 in the native membrane environment. The
      precursor is translocated into the channel interior, interacts with an internal
      loop, and inserts into the lateral gate by beta-signal exchange. Transport
      through the Omp85-channel interior followed by release through the lateral gate
      into the lipid phase may represent a basic mechanism for membrane insertion of
      beta-barrel proteins.

PMID- 29348216
TI  - Tamed immune reaction aids pregnancy.

PMID- 29348217
TI  - Tensions flare over electric fishing in European waters.

PMID- 29348218
TI  - Rochester roiled by fallout from sexual harassment case.

PMID- 29348219
TI  - Are algorithms good judges?

PMID- 29348220
TI  - The believer.

PMID- 29348221
TI  - Assessing nature's contributions to people.

PMID- 29348222
TI  - The art of manufacturing molecules.

PMID- 29348223
TI  - Quantum liquids get thin.

PMID- 29348224
TI  - A bacterial coat that is not pure cotton.

PMID- 29348225
TI  - Taking down defenses to improve vaccines.

PMID- 29348226
TI  - Remote control of nanoscale devices.

PMID- 29348227
TI  - Ben Barres (1954-2017).

PMID- 29348228
TI  - The pitfalls of taking science to the public.

PMID- 29348229
TI  - Vaccine mandates in France will save lives.

PMID- 29348230
TI  - Have your momos and eat them, too.

PMID- 29348232
TI  - A self-assembled nanoscale robotic arm controlled by electric fields.
AB  - The use of dynamic, self-assembled DNA nanostructures in the context of
      nanorobotics requires fast and reliable actuation mechanisms. We therefore
      created a 55-nanometer-by-55-nanometer DNA-based molecular platform with an
      integrated robotic arm of length 25 nanometers, which can be extended to more
      than 400 nanometers and actuated with externally applied electrical fields.
      Precise, computer-controlled switching of the arm between arbitrary positions on
      the platform can be achieved within milliseconds, as demonstrated with single
      pair Forster resonance energy transfer experiments and fluorescence microscopy.
      The arm can be used for electrically driven transport of molecules or
      nanoparticles over tens of nanometers, which is useful for the control of
      photonic and plasmonic processes. Application of piconewton forces by the robot
      arm is demonstrated in force-induced DNA duplex melting experiments.

PMID- 29348231
TI  - Genome-wide identification of interferon-sensitive mutations enables influenza
      vaccine design.
AB  - In conventional attenuated viral vaccines, immunogenicity is often suboptimal.
      Here we present a systematic approach for vaccine development that eliminates
      interferon (IFN)-modulating functions genome-wide while maintaining virus
      replication fitness. We applied a quantitative high-throughput genomics system to
      influenza A virus that simultaneously measured the replication fitness and IFN
      sensitivity of mutations across the entire genome. By incorporating eight IFN
      sensitive mutations, we generated a hyper-interferon-sensitive (HIS) virus as a
      vaccine candidate. HIS virus is highly attenuated in IFN-competent hosts but able
      to induce transient IFN responses, elicits robust humoral and cellular immune
      responses, and provides protection against homologous and heterologous viral
      challenges. Our approach, which attenuates the virus and promotes immune
      responses concurrently, is broadly applicable for vaccine development against
      other pathogens.

PMID- 29348233
TI  - Hydraulic fracturing volume is associated with induced earthquake productivity in
      the Duvernay play.
AB  - A sharp increase in the frequency of earthquakes near Fox Creek, Alberta, began
      in December 2013 in response to hydraulic fracturing. Using a hydraulic
      fracturing database, we explore relationships between injection parameters and
      seismicity response. We show that induced earthquakes are associated with
      completions that used larger injection volumes (104 to 105 cubic meters) and that
      seismic productivity scales linearly with injection volume. Injection pressure
      and rate have an insignificant association with seismic response. Further
      findings suggest that geological factors play a prominent role in seismic
      productivity, as evidenced by spatial correlations. Together, volume and
      geological factors account for ~96% of the variability in the induced earthquake
      rate near Fox Creek. This result is quantified by a seismogenic index-modified
      frequency-magnitude distribution, providing a framework to forecast induced
      seismicity.

PMID- 29348234
TI  - Chiromagnetic nanoparticles and gels.
AB  - Chiral inorganic nanostructures have high circular dichroism, but real-time
      control of their optical activity has so far been achieved only by irreversible
      chemical changes. Field modulation is a far more desirable path to chiroptical
      devices. We hypothesized that magnetic field modulation can be attained for
      chiral nanostructures with large contributions of the magnetic transition dipole
      moments to polarization rotation. We found that dispersions and gels of
      paramagnetic Co3O4 nanoparticles with chiral distortions of the crystal lattices
      exhibited chiroptical activity in the visible range that was 10 times as strong
      as that of nonparamagnetic nanoparticles of comparable size. Transparency of the
      nanoparticle gels to circularly polarized light beams in the ultraviolet range
      was reversibly modulated by magnetic fields. These phenomena were also observed
      for other nanoscale metal oxides with lattice distortions from imprinted amino
      acids and other chiral ligands. The large family of chiral ceramic nanostructures
      and gels can be pivotal for new technologies and knowledge at the nexus of
      chirality and magnetism.

PMID- 29348235
TI  - Digitization of multistep organic synthesis in reactionware for on-demand
      pharmaceuticals.
AB  - Chemical manufacturing is often done at large facilities that require a sizable
      capital investment and then produce key compounds for a finite period. We present
      an approach to the manufacturing of fine chemicals and pharmaceuticals in a self
      contained plastic reactionware device. The device was designed and constructed by
      using a chemical to computer-automated design (ChemCAD) approach that enables the
      translation of traditional bench-scale synthesis into a platform-independent
      digital code. This in turn guides production of a three-dimensional printed
      device that encloses the entire synthetic route internally via simple operations.
      We demonstrate the approach for the gamma-aminobutyric acid receptor agonist, (+/
      )-baclofen, establishing a concept that paves the way for the local manufacture
      of drugs outside of specialist facilities.

PMID- 29348236
TI  - A global atlas of the dominant bacteria found in soil.
AB  - The immense diversity of soil bacterial communities has stymied efforts to
      characterize individual taxa and document their global distributions. We analyzed
      soils from 237 locations across six continents and found that only 2% of
      bacterial phylotypes (~500 phylotypes) consistently accounted for almost half of
      the soil bacterial communities worldwide. Despite the overwhelming diversity of
      bacterial communities, relatively few bacterial taxa are abundant in soils
      globally. We clustered these dominant taxa into ecological groups to build the
      first global atlas of soil bacterial taxa. Our study narrows down the immense
      number of bacterial taxa to a "most wanted" list that will be fruitful targets
      for genomic and cultivation-based efforts aimed at improving our understanding of
      soil microbes and their contributions to ecosystem functioning.

PMID- 29348237
TI  - Improving refugee integration through data-driven algorithmic assignment.
AB  - Developed democracies are settling an increased number of refugees, many of whom
      face challenges integrating into host societies. We developed a flexible data
      driven algorithm that assigns refugees across resettlement locations to improve
      integration outcomes. The algorithm uses a combination of supervised machine
      learning and optimal matching to discover and leverage synergies between refugee
      characteristics and resettlement sites. The algorithm was tested on historical
      registry data from two countries with different assignment regimes and refugee
      populations, the United States and Switzerland. Our approach led to gains of
      roughly 40 to 70%, on average, in refugees' employment outcomes relative to
      current assignment practices. This approach can provide governments with a
      practical and cost-efficient policy tool that can be immediately implemented
      within existing institutional structures.

PMID- 29348239
TI  - From parade ground to PI.

PMID- 29348238
TI  - Phosphoethanolamine cellulose: A naturally produced chemically modified
      cellulose.
AB  - Cellulose is a major contributor to the chemical and mechanical properties of
      plants and assumes structural roles in bacterial communities termed biofilms. We
      find that Escherichia coli produces chemically modified cellulose that is
      required for extracellular matrix assembly and biofilm architecture. Solid-state
      nuclear magnetic resonance spectroscopy of the intact and insoluble material
      elucidates the zwitterionic phosphoethanolamine modification that had evaded
      detection by conventional methods. Installation of the phosphoethanolamine group
      requires BcsG, a proposed phosphoethanolamine transferase, with biofilm-promoting
      cyclic diguanylate monophosphate input through a BcsE-BcsF-BcsG transmembrane
      signaling pathway. The bcsEFG operon is present in many bacteria, including
      Salmonella species, that also produce the modified cellulose. The discovery of
      phosphoethanolamine cellulose and the genetic and molecular basis for its
      production offers opportunities to modulate its production in bacteria and
      inspires efforts to biosynthetically engineer alternatively modified cellulosic
      materials.

PMID- 29348241
TI  - Meet the First Authors.

PMID- 29348242
TI  - Anthracycline Cardiotoxicity: Worrisome Enough to Have You Quaking?

PMID- 29348240
TI  - Snf1-RELATED KINASE1-Controlled C/S1-bZIP Signaling Activates Alternative
      Mitochondrial Metabolic Pathways to Ensure Plant Survival in Extended Darkness.
AB  - Sustaining energy homeostasis is of pivotal importance for all living organisms.
      In Arabidopsis thaliana, evolutionarily conserved SnRK1 kinases (Snf1-RELATED
      KINASE1) control metabolic adaptation during low energy stress. To unravel
      starvation-induced transcriptional mechanisms, we performed transcriptome studies
      of inducible knockdown lines and found that S1-basic leucine zipper transcription
      factors (S1-bZIPs) control a defined subset of genes downstream of SnRK1. For
      example, S1-bZIPs coordinate the expression of genes involved in branched-chain
      amino acid catabolism, which constitutes an alternative mitochondrial respiratory
      pathway that is crucial for plant survival during starvation. Molecular analyses
      defined S1-bZIPs as SnRK1-dependent regulators that directly control
      transcription via binding to G-box promoter elements. Moreover, SnRK1 triggers
      phosphorylation of group C-bZIPs and the formation of C/S1-heterodimers and,
      thus, the recruitment of SnRK1 directly to target promoters. Subsequently, the
      C/S1-bZIP-SnRK1 complex interacts with the histone acetylation machinery to
      remodel chromatin and facilitate transcription. Taken together, this work reveals
      molecular mechanisms underlying how energy deprivation is transduced to reprogram
      gene expression, leading to metabolic adaptation upon stress.

PMID- 29348243
TI  - Improving Cell Production Techniques to Enhance Autologous Cell Therapy.

PMID- 29348244
TI  - Branch Point Smooth Muscle Cells Highlighted by Novel Lineage Tracking Approach.

PMID- 29348245
TI  - Induced Pluripotent Stem Cells Derived Extracellular Vesicles: A Potential
      Therapy for Cardiac Repair.

PMID- 29348247
TI  - Scot Matkovich: Keep on Keeping on.

PMID- 29348246
TI  - Global Overview of the Transnational Alliance for Regenerative Therapies in
      Cardiovascular Syndromes (TACTICS) Recommendations: A Comprehensive Series of
      Challenges and Priorities of Cardiovascular Regenerative Medicine.

PMID- 29348248
TI  - Texas Heart Institute International Symposium on Cardiovascular Regenerative
      Medicine.

PMID- 29348249
TI  - The (Translational) Road Less Traveled.

PMID- 29348250
TI  - T4 Translational Moonshot: Making Cardiovascular Discoveries Work for Everyone.

PMID- 29348252
TI  - Translational Research in Cardiovascular Repair: A Call for a Paradigm Shift.
AB  - The international consortium TACTICS (Transnational Alliance for Regenerative
      Therapies in Cardiovascular Syndromes) has recently addressed key priorities in
      the field of cell-based therapy for cardiac repair, identifying the efficacy of
      translational research as one of the main challenges to ultimately improve the
      quality of life of patients with ischemic disease. Much of the controversy and
      confusion surrounding cardiac regenerative therapy stems from insufficient rigor
      in the conduct of preclinical studies, and there is an increasing recognition of
      a number of problems that undermine its quality that may contribute to
      translational failure. Here, we introduce well defined stages for preclinical
      research, and put forth proposals that should promote more rigorous preclinical
      work, in an effort to improve its quality and translatability. To augment the
      utility of preclinical research and its translation, it is necessary to (1)
      improve the quality of preclinical research, (2) promote collaborative efforts,
      and (3) enhance the sharing of knowledge and protocols. In particular,
      confirmatory (stage III) preclinical studies should be considered as a preamble
      to clinical studies and therefore must adhere to their standards of quality
      (including internal validity, standardization of protocols, and multicenter
      design). To increase transparency and minimize bias, these studies should be
      prospectively registered in an independent, open database. Ultimately, these
      recommendations should be implemented in the daily routine of investigators and
      in the policies of institutions, journals, and funding agencies.

PMID- 29348251
TI  - Reducing Cardiovascular Disparities Through Community-Engaged Implementation
      Research: A National Heart, Lung, and Blood Institute Workshop Report.
AB  - Cardiovascular disparities remain pervasive in the United States. Unequal disease
      burden is evident among population groups based on sex, race, ethnicity,
      socioeconomic status, educational attainment, nativity, or geography. Despite the
      significant declines in cardiovascular disease mortality rates in all demographic
      groups during the last 50 years, large disparities remain by sex, race,
      ethnicity, and geography. Recent data from modeling studies, linked micromap
      plots, and small-area analyses also demonstrate prominent variation in
      cardiovascular disease mortality rates across states and counties, with an
      especially high disease burden in the southeastern United States and Appalachia.
      Despite these continued disparities, few large-scale intervention studies have
      been conducted in these high-burden populations to examine the feasibility of
      reducing or eliminating cardiovascular disparities. To address this challenge, on
      June 22 and 23, 2017, the National Heart, Lung, and Blood Institute convened
      experts from a broad range of biomedical, behavioral, environmental,
      implementation, and social science backgrounds to summarize the current state of
      knowledge of cardiovascular disease disparities and propose intervention
      strategies aligned with the National Heart, Lung, and Blood Institute mission.
      This report presents the themes, challenges, opportunities, available resources,
      and recommended actions discussed at the workshop.

PMID- 29348255
TI  - Hypertension and Atrial Fibrillation: Doubts and Certainties From Basic and
      Clinical Studies.
AB  - Hypertension and atrial fibrillation (AF) are 2 important public health
      priorities. Their prevalence is increasing worldwide, and the 2 conditions often
      coexist in the same patient. Hypertension and AF are strikingly related to an
      excess risk of cardiovascular disease and death. Hypertension ultimately
      increases the risk of AF, and because of its high prevalence in the population,
      it accounts for more cases of AF than other risk factors. Among patients with
      established AF, hypertension is present in about 60% to 80% of individuals.
      Despite the well-known association between hypertension and AF, several
      pathogenetic mechanisms underlying the higher risk of AF in hypertensive patients
      are still incompletely known. From an epidemiological standpoint, it is unclear
      whether the increasing risk of AF with blood pressure (BP) is linear or
      threshold. It is uncertain whether an intensive control of BP or the use of
      specific antihypertensive drugs, such as those inhibiting the renin-angiotensin
      aldosterone system, reduces the risk of subsequent AF in hypertensive patients in
      sinus rhythm. Finally, in spite of the observational evidence suggesting a
      progressive relation between BP levels and the risk of thromboembolism and
      bleeding in patients with hypertension and AF, the extent to which BP should be
      lowered in these patients, including those who undergo catheter ablation, remains
      uncertain. This article summarizes the main basic mechanisms through which
      hypertension is believed to promote AF. It also explores epidemiological data
      supporting an evolutionary pathway from hypertension to AF, including the
      emerging evidence favoring an intensive BP control or the use of drugs, which
      inhibit the renin-angiotensin-aldosterone system to reduce the risk of AF.
      Finally, it examines the impact of non-vitamin K antagonist oral anticoagulants
      compared with warfarin in relation to hypertension.

PMID- 29348254
TI  - Circulating Platelets as Mediators of Immunity, Inflammation, and Thrombosis.
AB  - Platelets, non-nucleated blood components first described over 130 years ago, are
      recognized as the primary cell regulating hemostasis and thrombosis. The vascular
      importance of platelets has been attributed to their essential role in
      thrombosis, mediating myocardial infarction, stroke, and venous thromboembolism.
      Increasing knowledge on the platelets' role in the vasculature has led to many
      advances in understanding not only how platelets interact with the vessel wall
      but also how they convey changes in the environment to other circulating cells.
      In addition to their well-described hemostatic function, platelets are active
      participants in the immune response to microbial organisms and foreign
      substances. Although incompletely understood, the immune role of platelets is a
      delicate balance between its pathogenic response and its regulation of thrombotic
      and hemostatic functions. Platelets mediate complex vascular homeostasis via
      specific receptors and granule release, RNA transfer, and mitochondrial secretion
      that subsequently regulates hemostasis and thrombosis, infection, and innate and
      adaptive immunity.

PMID- 29348253
TI  - Multifunctional Role of Chymase in Acute and Chronic Tissue Injury and
      Remodeling.
AB  - Chymase is the most efficient Ang II (angiotensin II)-forming enzyme in the human
      body and has been implicated in a wide variety of human diseases that also
      implicate its many other protease actions. Largely thought to be the product of
      mast cells, the identification of other cellular sources including cardiac
      fibroblasts and vascular endothelial cells demonstrates a more widely dispersed
      production and distribution system in various tissues. Furthermore, newly
      emerging evidence for its intracellular presence in cardiomyocytes and smooth
      muscle cells opens an entirely new compartment of chymase-mediated actions that
      were previously thought to be limited to the extracellular space. This review
      illustrates how these multiple chymase-mediated mechanisms of action can explain
      the residual risk in clinical trials of cardiovascular disease using conventional
      renin-angiotensin system blockade.

PMID- 29348257
TI  - Global sexual health education: STIF in Zambia.

PMID- 29348259
TI  - Thrombectomy stroke centers: The current threat to regionalizing stroke care.

PMID- 29348258
TI  - High-risk behaviour and HIV infection risk among non-local men who have sex with
      men with less than a single year's residence in urban centres: a multicentre
      cross-sectional study from China.
AB  - OBJECTIVES: Traditionally, subjects' migration status has usually been defined on
      the basis of their registered residency status. We attempted to redefine
      migration based on the duration of residency in their cities of migration and to
      explore more precisely the impact of migration on HIV infection risk in men who
      have sex with men (MSM). METHODS: A multisite cross-sectional study was conducted
      during 2012-2013 in seven Chinese cities. Questionnaire surveys were conducted
      and blood was drawn to test for antibodies to HIV, syphilis and herpes simplex
      virus-2 (HSV-2). MSM who were unregistered local residents and had resided in
      their cities of migration for <=1 or >1 year were defined as migrant MSM, or
      transitional MSM, respectively. RESULTS: Compared with transitional MSM and local
      MSM, migrant MSM had poorer HIV knowledge and higher rates of high-risk
      behaviour, including earlier sexual debut, multiple sexual partners,
      participation in commercial sex and recreational drug use. Multivariate logistic
      regression analysis showed that HIV prevalence among migrant MSM was higher than
      local MSM (p<0.05). This relationship, however, did not hold for transitional MSM
      and local MSM (p>0.05). Male sex work, recreational drug use, syphilis infection
      and HSV-2 infection were independently associated with HIV infection among
      migrant MSM. CONCLUSIONS: Non-local MSM with shorter residence were at greater
      risk of HIV acquisition. More focus should be placed on HIV behavioural
      interventions targeting non-local MSM with temporary residence.

PMID- 29348256
TI  - Flavonoids, Dairy Foods, and Cardiovascular and Metabolic Health: A Review of
      Emerging Biologic Pathways.
AB  - A growing body of nutritional science highlights the complex mechanisms and
      pleiotropic pathways of cardiometabolic effects of different foods. Among these,
      some of the most exciting advances are occurring in the area of flavonoids,
      bioactive phytochemicals found in plant foods; and in the area of dairy,
      including milk, yogurt, and cheese. Many of the relevant ingredients and
      mechanistic pathways are now being clarified, shedding new light on both the
      ingredients and the pathways for how diet influences health and well-being.
      Flavonoids, for example, have effects on skeletal muscle, adipocytes, liver, and
      pancreas, and myocardial, renal, and immune cells, for instance, related to 5'
      monophosphate-activated protein kinase phosphorylation, endothelial NO synthase
      activation, and suppression of NF-kappaB (nuclear factor-kappaB) and TLR4 (toll
      like receptor 4). Effects of dairy are similarly complex and may be mediated by
      specific amino acids, medium-chain and odd-chain saturated fats, unsaturated
      fats, branched-chain fats, natural trans fats, probiotics, vitamin K1/K2, and
      calcium, as well as by processing such as fermentation and homogenization. These
      characteristics of dairy foods influence diverse pathways including related to
      mammalian target of rapamycin, silent information regulator transcript-1,
      angiotensin-converting enzyme, peroxisome proliferator-activated receptors,
      osteocalcin, matrix glutamate protein, hepatic de novo lipogenesis, hepatic and
      adipose fatty acid oxidation and inflammation, and gut microbiome interactions
      such as intestinal integrity and endotoxemia. The complexity of these emerging
      pathways and corresponding biological responses highlights the rapid advances in
      nutritional science and the continued need to generate robust empirical evidence
      on the mechanistic and clinical effects of specific foods.

PMID- 29348260
TI  - The Canadian Preterm Birth Network: a study protocol for improving outcomes for
      preterm infants and their families.
AB  - BACKGROUND: Preterm birth (birth before 37 wk of gestation) occurs in about 8% of
      pregnancies in Canada and is associated with high mortality and morbidity rates
      that substantially affect infants, their families and the health care system. Our
      overall goal is to create a transdisciplinary platform, the Canadian Preterm
      Birth Network (CPTBN), where investigators, stakeholders and families will work
      together to improve childhood outcomes of preterm neonates. METHODS: Our national
      cohort will include 24 maternal-fetal/obstetrical units, 31 neonatal intensive
      care units and 26 neonatal follow-up programs across Canada with planned linkages
      to provincial health information systems. Three broad clusters of projects will
      be undertaken. Cluster 1 will focus on quality-improvement efforts that use the
      Evidence-based Practice for Improving Quality method to evaluate information from
      the CPTBN database and review the current literature, then identify potentially
      better health care practices and implement identified strategies. Cluster 2 will
      assess the impact of current practices and practice changes in maternal,
      perinatal and neonatal care on maternal, neonatal and neurodevelopmental
      outcomes. Cluster 3 will evaluate the effect of preterm birth on babies, their
      families and the health care system by integrating CPTBN data, parent feedback,
      and national and provincial database information in order to identify areas where
      more parental support is needed, and also generate robust estimates of resource
      use, cost and cost-effectiveness around preterm neonatal care. INTERPRETATION:
      These collaborative efforts will create a flexible, transdisciplinary, evaluable
      and informative research and quality-improvement platform that supports programs,
      projects and partnerships focused on improving outcomes of preterm neonates.

PMID- 29348262
TI  - Dawn of a New Era for Stroke Treatment: Implications of the DAWN Study for Acute
      Stroke Care and Stroke Systems of Care.

PMID- 29348261
TI  - Complement Receptor C5aR1 Plays an Evolutionarily Conserved Role in Successful
      Cardiac Regeneration.
AB  - BACKGROUND: Defining conserved molecular pathways in animal models of successful
      cardiac regeneration could yield insight into why adult mammals have inadequate
      cardiac regeneration after injury. Insight into the transcriptomic landscape of
      early cardiac regeneration from model organisms will shed light on evolutionarily
      conserved pathways in successful cardiac regeneration. METHODS: Here we describe
      a cross-species transcriptomic screen in 3 model organisms for cardiac
      regeneration: axolotl, neonatal mice, and zebrafish. Apical resection to remove
      ~10% to 20% of ventricular mass was carried out in these model organisms. RNA
      sequencing analysis was performed on the hearts harvested at 3 time points: 12,
      24, and 48 hours after resection. Sham surgery was used as internal control.
      RESULTS: Genes associated with inflammatory processes were found to be
      upregulated in a conserved manner. Complement receptors (activated by complement
      components, part of the innate immune system) were found to be highly upregulated
      in all 3 species. This approach revealed induction of gene expression for
      complement 5a receptor 1 in the regenerating hearts of zebrafish, axolotls, and
      mice. Inhibition of complement 5a receptor 1 significantly attenuated the
      cardiomyocyte proliferative response to heart injury in all 3 species.
      Furthermore, after left ventricular apical resection, the cardiomyocyte
      proliferative response was diminished in mice with genetic deletion of complement
      5a receptor 1. CONCLUSIONS: These data reveal that activation of complement 5a
      receptor 1 mediates an evolutionarily conserved response that promotes
      cardiomyocyte proliferation after cardiac injury and identify complement pathway
      activation as a common pathway of successful heart regeneration.

PMID- 29348263
TI  - Phosphoinositide 3-Kinase Gamma Inhibition Protects From Anthracycline
      Cardiotoxicity and Reduces Tumor Growth.
AB  - BACKGROUND: Anthracyclines, such as doxorubicin (DOX), are potent anticancer
      agents for the treatment of solid tumors and hematologic malignancies. However,
      their clinical use is hampered by cardiotoxicity. This study sought to
      investigate the role of phosphoinositide 3-kinase gamma (PI3Kgamma) in DOX
      induced cardiotoxicity and the potential cardioprotective and anticancer effects
      of PI3Kgamma inhibition. METHODS: Mice expressing a kinase-inactive PI3Kgamma or
      receiving PI3Kgamma-selective inhibitors were subjected to chronic DOX treatment.
      Cardiac function was analyzed by echocardiography, and DOX-mediated signaling was
      assessed in whole hearts or isolated cardiomyocytes. The dual cardioprotective
      and antitumor action of PI3Kgamma inhibition was assessed in mouse mammary tumor
      models. RESULTS: PI3Kgamma kinase-dead mice showed preserved cardiac function
      after chronic low-dose DOX treatment and were protected against DOX-induced
      cardiotoxicity. The beneficial effects of PI3Kgamma inhibition were causally
      linked to enhanced autophagic disposal of DOX-damaged mitochondria. Consistently,
      either pharmacological or genetic blockade of autophagy in vivo abrogated the
      resistance of PI3Kgamma kinase-dead mice to DOX cardiotoxicity. Mechanistically,
      PI3Kgamma was triggered in DOX-treated hearts, downstream of Toll-like receptor
      9, by the mitochondrial DNA released by injured organelles and contained in
      autolysosomes. This autolysosomal PI3Kgamma/Akt/mTOR/Ulk1 signaling provided
      maladaptive feedback inhibition of autophagy. PI3Kgamma blockade in models of
      mammary gland tumors prevented DOX-induced cardiac dysfunction and concomitantly
      synergized with the antitumor action of DOX by unleashing anticancer immunity.
      CONCLUSIONS: Blockade of PI3Kgamma may provide a dual therapeutic advantage in
      cancer therapy by simultaneously preventing anthracyclines cardiotoxicity and
      reducing tumor growth.

PMID- 29348264
TI  - Employment among Patients Starting Dialysis in the United States.
AB  - BACKGROUND AND OBJECTIVES: Patients with ESRD face significant challenges to
      remaining employed. It is unknown when in the course of kidney disease patients
      stop working. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We examined
      employment trends over time among patients ages 18-54 years old who initiated
      dialysis in the United States between 1996 and 2013 from a national ESRD
      registry. We compared unadjusted trends in employment at the start of dialysis
      and 6 months before ESRD and used linear probability models to estimate changes
      in employment over time after adjusting for patient characteristics and local
      unemployment rates in the general population. We also examined employment among
      selected vulnerable patient populations and changes in employment in the 6 months
      preceding dialysis initiation. RESULTS: Employment was low among patients
      starting dialysis throughout the study period at 23%-24%, and 38% of patients who
      were employed 6 months before ESRD stopped working by dialysis initiation.
      However, after adjusting for observed characteristics, the probability of
      employment increased over time; patients starting dialysis between 2008 and 2013
      had a 4.7% (95% confidence interval, 4.3% to 5.1%) increase in the absolute
      probability of employment at the start of dialysis compared with patients
      starting dialysis between 1996 and 2001. Black and Hispanic patients were less
      likely to be employed than other patients starting dialysis, but this gap
      narrowed during the study period. CONCLUSIONS: Although working-aged patients in
      the United States starting dialysis have experienced increases in the adjusted
      probability of employment over time, employment at the start of dialysis has
      remained low.

PMID- 29348265
TI  - Employment among Patients on Dialysis: An Unfulfilled Promise.

PMID- 29348266
TI  - Dopamine Receptor Agonist Treatment of Idiopathic Dystonia: A Reappraisal in
      Humans and Mice.
AB  - Although dystonia is often associated with abnormal dopamine neurotransmission,
      dopaminergic drugs are not currently used to treat dystonia because there is a
      general view that dopaminergic drugs are ineffective. However, there is little
      conclusive evidence to support or refute this assumption. Therefore, to assess
      the therapeutic potential of these compounds, we analyzed results from multiple
      trials of dopamine receptor agonists in patients with idiopathic dystonias and
      also tested the efficacy of dopamine receptor agonists in a mouse model of
      generalized dystonia. Our results suggest that dopamine receptor agonists were
      effective in some, but not all, patients tested. Further, the mixed D1/D2
      dopamine receptor agonist apomorphine was apparently more effective than subtype
      selective D2 dopamine receptor agonists. However, rigorously controlled trials
      are still needed. In a mouse model of dystonia, a selective D1 dopamine receptor
      agonist was not effective while a selective D2 dopamine receptor had modest
      efficacy. However, when combined, these receptor-selective agonists acted
      synergistically to ameliorate the dystonia. Coactivation of D1 and D2 dopamine
      receptors using apomorphine or by increasing extracellular concentrations of
      dopamine was also effective. Thus, results from both clinical trials and tests in
      mice suggest that coactivation of D1 and D2 dopamine receptors may be an
      effective therapeutic strategy in some patients. These results support a
      reconsideration of dopamine receptors as targets for the treatment of dystonia,
      particularly because recent genetic and diagnostic advances may facilitate the
      identification of the subtypes of dystonia patients who respond and those who do
      not.

PMID- 29348268
TI  - Is the Quest for Signaling Bias Worth the Effort?
AB  - The question of whether signaling bias is a viable discovery strategy for drug
      therapy is discussed as a value proposition. On the positive side, bias is easily
      identified and quantified in simple in vitro functional assays with little
      resource expenditure. However, there are valid pharmacological reasons why these
      in vitro bias numbers may not accurately translate to in vivo therapeutic systems
      making the expectation of direct correspondence of in vitro bias to in vivo
      systems a problematic process. Presently, in vitro bias is used simply as a means
      to identify unique molecules to be advanced to more complex therapeutic assays
      but from this standpoint alone, the value proposition lies far to the positive.
      However, pharmacological attention needs to be given to the translational gap to
      reduce inevitable and costly attrition in biased molecule progression.

PMID- 29348267
TI  - Toll-Like Receptor 9-Dependent AMPKalpha Activation Occurs via TAK1 and
      Contributes to RhoA/ROCK Signaling and Actin Polymerization in Vascular Smooth
      Muscle Cells.
AB  - Traditionally, Toll-like receptor 9 (TLR9) signals through an MyD88-dependent
      cascade that results in proinflammatory gene transcription. Recently, it was
      reported that TLR9 also participates in a stress tolerance signaling cascade in
      nonimmune cells. In this noncanonical pathway, TLR9 binds to and inhibits
      sarcoplasmic/endoplasmic reticulum Ca2+-ATPase 2 (SERCA2), modulating
      intracellular calcium handling, and subsequently resulting in the activation of
      5'-AMP-activated protein kinase alpha (AMPKalpha). We have previously reported
      that TLR9 causes increased contraction in isolated arteries; however, the
      mechanisms underlying this vascular dysfunction need to be further clarified.
      Therefore, we hypothesized that noncanonical TLR9 signaling was also present in
      vascular smooth muscle cells (VSMCs) and that it mediates enhanced contractile
      responses through SERCA2 inhibition. To test these hypotheses, aortic microsomes,
      aortic VSMCs, and isolated arteries from male Sprague-Dawley rats were incubated
      with vehicle or TLR9 agonist (ODN2395). Despite clear AMPKalpha activation after
      treatment with ODN2395, SERCA2 activity was unaffected. Alternatively, ODN2395
      caused the phosphorylation of AMPKalpha via transforming growth factor beta
      activated kinase 1 (TAK1), a kinase involved in TLR9 inflammatory signaling.
      Downstream, we hypothesized that that TLR9 activation of AMPKalpha may be
      important in mediating actin cytoskeleton reorganization. ODN2395 significantly
      increased the filamentous-to-globular actin ratio, as well as indices of RhoA/Rho
      associated protein kinase (ROCK) activation, with the latter being prevented by
      AMPKalpha inhibition. In conclusion, AMPKalpha phosphorylation after TLR9
      activation in VSMCs appears to be an extension of traditional inflammatory
      signaling via TAK1, as opposed to SERCA2 inhibition and the noncanonical pathway.
      Nonetheless, TLR9-AMPKalpha signaling can mediate VSMC function via RhoA/ROCK
      activation and actin polymerization.

PMID- 29348269
TI  - Management of incidental adrenal tumours.

PMID- 29348270
TI  - Hyperpigmentation in the skin folds.

PMID- 29348271
TI  - Intratumoral Payload Concentration Correlates with the Activity of Antibody-Drug
      Conjugates.
AB  - Antibody-drug conjugates (ADC) have become important scaffolds for targeted
      cancer therapies. However, ADC exposure-response correlation is not well
      characterized. We demonstrated that intratumor payload exposures correlated well
      with the corresponding efficacies of several disulfide-linked ADCs, bearing an
      DNA alkylating agent, pyrrolo[2,1-c][1,4]benzodiazepine-dimer (PBD), in HER2
      expressing xenograft models. The correlation suggests that a threshold
      concentration of intratumor payload is required to support sustained efficacy and
      an ADC can deliver an excessive level of payload to tumors that does not enhance
      efficacy ("Plateau" effect). In contrast to tumor PBD concentrations, related
      assessments of systemic exposures, plasma stability, and drug-to-antibody ratio
      changes of related ADCs did not consistently rationalize the observed ADC
      efficacies. A minimal efficacious dose could be determined by ADC dose
      fractionation studies in the xenograft models. Mechanistic investigations
      revealed that both linker immolation and linker disulfide stability are the key
      factors that determine intratumor PBD concentrations. Overall, this study
      demonstrates how a linker design can impact ADC efficacy and that the intratumor
      exposure of a payload drug as the molecular mechanism quantitatively correlate
      with and predict the antitumor efficacy of ADCs. Mol Cancer Ther; 17(3); 677-85.
      (c)2018 AACR.

PMID- 29348273
TI  - Correction: optic disc swelling in a patient with tuberculous meningitis: a
      diagnostic challenge.

PMID- 29348272
TI  - Use of Computer Technology During Family-Centered Rounds: A Qualitative Study of
      Parent Perspectives.
AB  - OBJECTIVES: Physicians often use computer technologies to assist in work
      activities, including family-centered rounds (FCR), but little is known about the
      attitudes of families on the use of these technologies. We aimed to describe
      these perceptions on the presence and use of computer technologies during FCR.
      METHODS: We conducted observations of FCR from a parent's visual perspective to
      "see what they see." This was followed by in-depth interviews with the families
      of patients admitted to the hospitalist service at our institution to describe
      their experience with the use of computer technology by the medical team during
      FCR. RESULTS: From the analysis of 31 individual interview transcripts, our
      research team identified the following 4 themes: (1) technology serves a purpose
      during FCR; (2) to view data in real time; (3) do not lose the human connection;
      and (4) transparency is valued. Thirty-eight observations showed broad use of
      computer technologies by the medical team. Devices were used to provide data that
      would educate the family; however, the devices were often placed between the
      medical team and family, creating a physical barrier. CONCLUSIONS: Families
      recognized the benefit of computer technologies in the care of their child and
      would like greater sharing of information by the medical team. They insisted
      their child always be "placed first" and that the team be transparent with their
      use of technology. Computer technology may create possible obstructions and
      distractions to the medical team. As computer technologies become more
      commonplace in medicine, maintaining the essence of good patient-communication
      and family centered care is essential.

PMID- 29348274
TI  - Sinogenic intracranial complications: is adalimumab a culprit?
AB  - We present two 11-year-old girls with chronic recurrent multifocal osteomyelitis,
      treated with adalimumab. Both developed severe intracranial complications to
      sinusitis. Patient 1 had been treated with adalimumab for 15 months when she
      developed acute sinusitis complicated by an orbital abscess, forehead swelling, a
      subdural empyema and osteomyelitis of the frontal bone. She was treated with a
      rhinosurgical and neurosurgical approach with intravenous antibiotics.Patient 2
      had been in adalimumab treatment for 10 weeks. Adalimumab was discontinued 8
      weeks prior to developing subdural empyema and subcortical abscesses in
      combination with sinusitis. She was treated with endoscopic sinus surgery and
      intravenous antibiotics. Both patients had developed psoriasis and episodes of
      infection during treatment. They were non-septic and had low fever on
      presentation. None of the patients suffered any long-term neurological sequelae.
      The immunosuppressive treatment with adalimumab is considered to be the cause of
      the sinogenic intracranial complications in our cases.

PMID- 29348275
TI  - Microangiopathies in pregnancy.
AB  - Thrombotic thrombocytopenic purpura (TTP) is a potentially reversible, life
      threatening medical emergency. We present a case of a 21-year-old female with
      evidence of haemolytic anaemia based on the presence of positive markers of
      haemolysis. Negative Coomb's test, thrombocytopenia and placental infarcts raised
      suspicion for a thrombotic microangiopathy. She was diagnosed with TTP and
      managed with emergency plasma exchange. Her recovery was immediate.A presumptive
      diagnosis of TTP should be based on the presence of microangiopathic haemolytic
      anaemia with thrombocytopenia and plasma exchange should be initiated while
      complete work up is pending. Using the regular pentad solely for diagnosis of TTP
      will lead to underdiagnosis of many cases and should be avoided.Several
      microangiopathies can be seen during pregnancy including TTP/atypical haemolytic
      uraemic syndrome, HELLP syndrome, pre-eclampsia, disseminated intravascular
      coagulopathy and antiphospholipid antibody syndrome. Distinction between each
      type will be the focus of our discussion as treatment decisions differ
      accordingly.

PMID- 29348276
TI  - Congenital tuberculosis presenting as otorrhoea in a preterm infant.
AB  - A premature infant of 25 weeks' gestational age presented at 8 weeks after birth
      with otorrhoea from the left ear. Following a course of topical and systemic
      antibiotics, the patient deteriorated developing facial nerve paralysis and
      cervical lymphadenitis. Contrast-enhanced CT and MRI of the head showed a
      destructive process of the left temporal bone. These findings prompted the
      clinicians to send swabs from the purulent discharge from the ear for acid-fast
      bacilli stain. Furthermore, surgical exploration and debridement were undertaken.
      Cultures from ear discharge and biopsy-taken during surgical procedure-revealed
      the presence of Mycobacterium tuberculosis complex. The patient developed
      necrotizing otitis media, left temporal bone osteomyelitis and cervical
      lymphadenitis. The infant's mother was found to have an endometrial biopsy
      positive for M. tuberculosis suggesting the diagnosis of congenital tuberculosis.

PMID- 29348277
TI  - Chronic strongyloidiasis with recurrent asthma exacerbations and steroid
      associated 'hives'.
AB  - A 74-year-old man experienced worsening asthma for several years. Oral steroids
      were required on multiple occasions for asthma treatment. During his steroid
      courses, he developed a hive-like rash, which would resolve after completion of
      each steroid course. He was from Romania, and had lived in the USA for many
      years. Laboratory testing had shown eosinophilia. He was eventually diagnosed
      with strongyloidiasis by serology. Treatment with ivermectin led to marked
      improvement but not resolution of his long-term asthma. His hive-like rash, which
      was likely larva currens, did not recur with a subsequent steroid course.
      Improved recognition of strongyloidiasis, particularly in steroid-treated
      patients, is needed.

PMID- 29348279
TI  - 'Clinically suspected myocarditis with pseudoinfarct presentation' complicated
      with left ventricular aneurysm.
AB  - A 51-year-old man presented with chest pain, high troponin level, inflammatory
      syndrome and ST-segment elevation in the anterior leads. While the transthoracic
      echocardiogram (TTE) showed anteroseptal hypokinesis and apical akinesis, the
      coronary angiogram was normal. Cardiac MR demonstrated a typical aspect of
      myocarditis (multiple areas of mid-myocardial late gadolinium enhancement,
      sparing the subendocardial layer, along with oedema). The initial diagnosis was
      clinically suspected myocarditis with pseudoinfarct presentation. However, the
      short-term evolution was not typical of this syndrome, since an apical transmural
      scar with aneurysm developed within 2 weeks. Seven years later, the patient
      remained asymptomatic, while Q waves persisted in anterior leads along with an
      apical aneurysm on TTE. A transmural myocardial necrosis with aneurysm is an
      unusual complication of acute myocarditis. The potential mechanisms accounting
      for the development of these lesions are reviewed, and the clinical implications
      for the diagnosis and monitoring of acute myocarditis are discussed.

PMID- 29348278
TI  - A ping-pong ball in left atrium.

PMID- 29348280
TI  - Marked cachexia in probable invasive pulmonary aspergillosis with bronchopleural
      fistula.
AB  - A 49-year-old man with a medical history of diabetes and heavy smoking was
      admitted to intensive care with severe bilateral pneumonia associated with marked
      cachexia. He developed a complex right-sided bronchopleural fistula and was
      transferred to our tertiary centre for consideration of surgical
      intervention.Despite escalation of antibiotic therapy, he did not improve and
      further investigations led to a diagnosis of invasive pulmonary aspergillosis.
      Definitive treatment plans required a right pneumonectomy; however, given the
      severity of cachexia, he remained unable to undergo such a large operation. This
      case demonstrates an atypical presentation of invasive pulmonary aspergillosis in
      a mildly immunodeficient individual. It highlights the challenges in assessment
      and management of critically ill patients' nutrition as well as optimal timing
      for surgical intervention.

PMID- 29348281
TI  - Early intrauterine pregnancy during major surgery: the importance of preoperative
      assessment and advice.
AB  - We present a case of a live birth occurring post radical laparoscopic excision of
      endometriosis, hysteroscopy, curettage and test of tubal patency in the presence
      of an early intrauterine gestation.

PMID- 29348282
TI  - Acquired pyloric stenosis resulting in hypokalaemic, hyperchloraemic normal anion
      gap metabolic acidosis. Persistent vomiting in an adult: cause and effect.
AB  - A 24-year-old woman presented with a history of persistent vomiting for at least
      3 months. This resulted in severe dehydration with risk of acute kidney injury.
      In addition to volume depletion, loss of gastric fluid resulted in a specific
      metabolic derangement-hypokalaemic, hypochloraemic normal anion gap metabolic
      alkalosis with a reduced ionised calcium concentration and paradoxical aciduria.
      These metabolic changes were reflected in her ECG. Investigation demonstrated
      acquired gastric outflow tract obstruction secondary to a pyloric peptic ulcer.
      The patient was resuscitated with intravenous crystalloid and electrolyte
      supplements. The acquired pyloric stenosis was treated medically with a proton
      pump inhibitor and Helicobacter pylori eradication therapy with excellent
      recovery.

PMID- 29348283
TI  - Unusual 'feathery' cause of a parapharyngeal abscess in an infant.
AB  - A 7-month-old boy presented to the emergency department with reduced oral intake,
      neck swelling and fever. Clinical examination revealed a 3 cm left parotid and
      left level I neck swelling with left medialised tonsil but no trismus. Computed
      imaging confirmed the presence of an abscess in the peritonsillar area with
      extension into the parapharyngeal space and deep lobe of the parotid gland. The
      abscess was incised and drained transorally. Following drainage of the abscess, a
      small 3 mm suspicious foreign body was seen. After extraction, this was revealed
      to be a 60 mm feather. We would like to highlight this unusual case in an infant
      and to ensure that foreign body is considered as aetiology. There are only a
      handful of cases in the literature involving feathers causing neck abscesses and,
      to our knowledge, this is the first case where the patient presented with a
      pharyngeal abscess, which was drained transorally.

PMID- 29348284
TI  - Laryngeal tuberculosis: a rare cause of critical airway obstruction.
AB  - Laryngeal tuberculosis (TB) is a rare condition, occurring in less than 1% of
      patients infected with pulmonary TB. We present a case of a 57-year-old male
      patient, who presented in extremis with audible stridor, increased work of
      breathing and cyanosis. In addition, the patient had a complex medical history,
      including a recent diagnosis of congenital malformation of the epiglottis.
      Emergency intervention was required to secure the airway, and after initial
      attempts at intubation were unsuccessful, an emergency tracheostomy was
      performed. Four days after initial presentation, his sputum tested positive for
      acid-fast bacilli, and a subsequent CT chest revealed pulmonary as well as
      laryngeal TB, which was confirmed on biopsy of the larynx. The patient was
      commenced on a 24-week course of anti-tuberculous treatment and was successfully
      decannulated 6 months after the emergency airway was established.

PMID- 29348285
TI  - Vancomycin-induced coronary artery spasm: a case of Kounis syndrome.
AB  - Kounis syndrome defined as the appearance of acute coronary syndrome in the
      context of an allergic reaction is a relatively rare phenomenon. There are three
      variants of this syndrome in which the patient presents with symptoms of an acute
      chest. Herein, we describe a case of an 83-year-old woman who demonstrated type I
      variant of Kounis syndrome in response to vancomycin administration. After
      initialisation of vancomycin, she became unresponsive and an ECG demonstrated ST
      changes consistent with inferior-lateral myocardial infarction. Once allergic
      stimulus was removed, ECG normalised. Differential diagnosis includes, myocardial
      infarctions, angina as well as intravascular stent thrombosis, which must all be
      ruled out. The patient was monitored and discharged soon thereafter.

PMID- 29348286
TI  - Portal vein embolisation in a patient with situs inversus.
AB  - Portal vein embolisation (PVE) is a well-established technique used for patients
      who require major hepatic resections without sufficient volume of future remnant
      liver (FRL). We describe a case of PVE in a patient with situs inversus. Computed
      Tomography (CT) 4 weeks after the procedure demonstrated significant hypertrophy
      of the FRL. However, the surgical procedure was aborted due to signs of
      extrahepatic progression.

PMID- 29348287
TI  - Recurrent hiccups may signal brainstem pathology and should be investigated.
AB  - While occasional hiccups are normal, their persistent recurrence is distressing
      and may have an underlying aetiology. Patients with recurrent hiccups may undergo
      a long journey and see many physicians before the diagnosis is finally made. The
      purpose of this report is to increase awareness of central nervous system lesions
      as a possible cause for recurrent hiccups and provide an illustrative case of an
      otherwise fit man presenting with ongoing hiccups caused by a medullary
      haemangioblastoma.

PMID- 29348288
TI  - Budd-Chiari syndrome: a rare and life-threatening complication of Crohn's
      disease.
AB  - Budd-Chiari syndrome (BCS) is characterised by obstruction of hepatic venous
      outflow and may be triggered by the prothrombotic state associated with
      inflammatory bowel disease (IBD). We reported a case of Crohn's disease (CD) that
      presented with anasarca, ascites, symptomatic hepatomegaly, elevated liver
      enzymes, increased prothrombin time and low albumin. Oesophagogastroduodenoscopy
      and colonoscopy confirmed active CD. Abdominal CT showed hepatic vein thrombosis.
      Liver biopsy revealed severe perivenular sinusoidal dilation with areas of
      hepatocyte dropout, bands of hepatocyte atrophy and centrizonal fibrosis,
      suggestive of BCS. The patient was treated with steroids for CD and systemic
      anticoagulants for BCS. His liver function and enzymes normalised, and he
      reported symptomatic improvement. The precise mechanism responsible for increased
      hypercoagulability in IBD remains unclear. Early recognition and treatment for
      possible thrombotic complications of CD is critical to prevent potentially fatal
      events like pulmonary embolism or liver failure.

PMID- 29348289
TI  - Urinary Bladder Mass Due To Chronic Lymphocytic Leukaemia.

PMID- 29348290
TI  - An unusual case of basilar artery aneurysm presenting with spastic quadriparesis.
AB  - Unruptured aneurysm usually presents with headache and neuro-ophthalmic features;
      when it ruptures, it presents with subarachnoid haemorrhage. Basilar artery
      aneurysm represents only 3-5% of cerebral aneurysms. Non-haemorrhagic symptoms
      and the signs of unruptured aneurysms are manifested as mass effect,
      thromboembolic phenomenon or epileptical attacks. Clinical presentation of
      unruptured aneurysm depends on structures which are involved. In our case, the
      patient had insidious onset headache and spastic quadriparesis with sixth cranial
      nerve palsy, which implicate involvement of corticospinal pathways at the level
      of pons.

PMID- 29348291
TI  - Bruns nystagmus: an important clinical clue for cerebellopontine angle tumours.

PMID- 29348292
TI  - Morbid jealousy reactivated by mood episodes.
AB  - A middle-aged man who has been enduring financial constraint experienced a period
      of irritability, increased goal-directed activities and insomnia occurring along
      with extreme jealousy with his current wife. The episode was followed by
      depressed mood and non-prominent auditory hallucination. His previous history
      revealed a forensic psychiatry case of a murder he committed 20 years ago.

PMID- 29348293
TI  - Defining limited stage small cell lung cancer: a radiation oncologist's
      perspective.

PMID- 29348294
TI  - Sarcomatoid carcinoma of the duodenum.

PMID- 29348296
TI  - CART Targeting of Solid Tumors: More Pieces to the Puzzle.
AB  - Chimeric antigen receptor-modified T (CART)-cell-based targeting of solid tumors
      remains a considerable and worthwhile challenge in the field of immunotherapy.
      The role of chemotherapy to target stroma and enhance chimeric antigen receptor
      (CAR) cell antitumor function, expansion, and persistence is still unresolved.
      Clin Cancer Res; 24(6); 1246-7. (c)2018 AACRSee related article by Guo et al., p.
      1277.

PMID- 29348295
TI  - Tuning CRISPR-Cas9 Gene Drives in Saccharomyces cerevisiae.
AB  - Control of biological populations is an ongoing challenge in many fields,
      including agriculture, biodiversity, ecological preservation, pest control, and
      the spread of disease. In some cases, such as insects that harbor human pathogens
      (e.g., malaria), elimination or reduction of a small number of species would have
      a dramatic impact across the globe. Given the recent discovery and development of
      the CRISPR-Cas9 gene editing technology, a unique arrangement of this system, a
      nuclease-based "gene drive," allows for the super-Mendelian spread and forced
      propagation of a genetic element through a population. Recent studies have
      demonstrated the ability of a gene drive to rapidly spread within and nearly
      eliminate insect populations in a laboratory setting. While there are still
      ongoing technical challenges to design of a more optimal gene drive to be used in
      wild populations, there are still serious ecological and ethical concerns
      surrounding the nature of this powerful biological agent. Here, we use budding
      yeast as a safe and fully contained model system to explore mechanisms that might
      allow for programmed regulation of gene drive activity. We describe four
      conserved features of all CRISPR-based drives and demonstrate the ability of each
      drive component-Cas9 protein level, sgRNA identity, Cas9 nucleocytoplasmic
      shuttling, and novel Cas9-Cas9 tandem fusions-to modulate drive activity within a
      population.

PMID- 29348297
TI  - Changes in macrophage transcriptome associate with systemic sclerosis and mediate
      GSDMA contribution to disease risk.
AB  - OBJECTIVES: Several common and rare risk variants have been reported for systemic
      sclerosis (SSc), but the effector cell(s) mediating the function of these genetic
      variants remains to be elucidated. While innate immune cells have been proposed
      as the critical targets to interfere with the disease process underlying SSc, no
      studies have comprehensively established their effector role. Here we
      investigated the contribution of monocyte-derived macrophages (MDMs) in mediating
      genetic susceptibility to SSc. METHODS: We carried out RNA sequencing and genome
      wide genotyping in MDMs from 57 patients with SSc and 15 controls. Our
      differential expression and expression quantitative trait locus (eQTL) analysis
      in SSc was further integrated with epigenetic, expression and eQTL data from
      skin, monocytes, neutrophils and lymphocytes. RESULTS: We identified 602 genes
      upregulated and downregulated in SSc macrophages that were significantly enriched
      for genes previously implicated in SSc susceptibility (P=5*10-4), and 270 cis
      regulated genes in MDMs. Among these, GSDMA was reported to carry an SSc risk
      variant (rs3894194) regulating expression of neighbouring genes in blood. We show
      that GSDMA is upregulated in SSc MDMs (P=8.4*10-4) but not in the skin, and is a
      significant eQTL in SSc macrophages and lipopolysaccharide/interferon gamma
      (IFNgamma)-stimulated monocytes. Furthermore, we identify an SSc macrophage
      transcriptome signature characterised by upregulation of glycolysis, hypoxia and
      mTOR signalling and a downregulation of IFNgamma response pathways. CONCLUSIONS:
      Our data further establish the link between macrophages and SSc, and suggest that
      the contribution of the rs3894194 risk variant to SSc susceptibility can be
      mediated by GSDMA expression in macrophages.

PMID- 29348299
TI  - Seven days in medicine: 10-16 January 2018.

PMID- 29348300
TI  - Letter to the GMC chair regarding Hadiza Bawa-Garba.

PMID- 29348298
TI  - A Review of Prostate Cancer Genome-Wide Association Studies (GWAS).
AB  - Prostate cancer is the most common cancer in men in Europe and the United States.
      The genetic heritability of prostate cancer is contributed to by both rarely
      occurring genetic variants with higher penetrance and moderate to commonly
      occurring variants conferring lower risks. The number of identified variants
      belonging to the latter category has increased dramatically in the last 10 years
      with the development of the genome-wide association study (GWAS) and the
      collaboration of international consortia that have led to the sharing of large
      scale genotyping data. Over 40 prostate cancer GWAS have been reported, with
      approximately 170 common variants now identified. Clinical utility of these
      variants could include strategies for population-based risk stratification to
      target prostate cancer screening to men with an increased genetic risk of disease
      development, while for those who develop prostate cancer, identifying genetic
      variants could allow treatment to be tailored based on a genetic profile in the
      early disease setting. Functional studies of identified variants are needed to
      fully understand underlying mechanisms of disease and identify novel targets for
      treatment. This review will outline the GWAS carried out in prostate cancer and
      the common variants identified so far, and how these may be utilized clinically
      in the screening for and management of prostate cancer. Cancer Epidemiol
      Biomarkers Prev; 27(8); 845-57. (c)2018 AACR.

PMID- 29348301
TI  - Predicting the presence of macrovascular causes in non-traumatic intracerebral
      haemorrhage: the DIAGRAM prediction score.
AB  - OBJECTIVE: A substantial part of non-traumatic intracerebral haemorrhages (ICH)
      arises from a macrovascular cause, but there is little guidance on selection of
      patients for additional diagnostic work-up. We aimed to develop and externally
      validate a model for predicting the probability of a macrovascular cause in
      patients with non-traumatic ICH. METHODS: The DIagnostic AngioGRAphy to find
      vascular Malformations (DIAGRAM) study (n=298; 69 macrovascular cause; 23%) is a
      prospective, multicentre study assessing yield and accuracy of CT angiography
      (CTA), MRI/ magnetic resonance angiography (MRA) and intra-arterial catheter
      angiography in diagnosing macrovascular causes in patients with non-traumatic
      ICH. We considered prespecified patient and ICH characteristics in multivariable
      logistic regression analyses as predictors for a macrovascular cause. We combined
      independent predictors in a model, which we validated in an external cohort of
      173 patients with ICH (78 macrovascular cause, 45%). RESULTS: Independent
      predictors were younger age, lobar or posterior fossa (vs deep) location of ICH,
      and absence of small vessel disease (SVD). A model that combined these predictors
      showed good performance in the development data (c-statistic 0.83; 95% CI 0.78 to
      0.88) and moderate performance in external validation (c-statistic 0.66; 95% CI
      0.58 to 0.74). When CTA results were added, the c-statistic was excellent (0.91;
      95% CI 0.88 to 0.94) and good after external validation (0.88; 95% CI 0.83 to
      0.94). Predicted probabilities varied from 1% in patients aged 51-70 years with
      deep ICH and SVD, to more than 50% in patients aged 18-50 years with lobar or
      posterior fossa ICH without SVD. CONCLUSION: The DIAGRAM scores help to predict
      the probability of a macrovascular cause in patients with non-traumatic ICH based
      on age, ICH location, SVD and CTA.

PMID- 29348303
TI  - Absence epilepsy beyond adolescence: an outcome analysis after 45 years of follow
      up.
AB  - OBJECTIVES: Depending on patient age at onset, absence epilepsy is subdivided
      into childhood and juvenile forms. Absence seizures can occur several times per
      day (pyknoleptic course) or less frequently than daily (non-pyknoleptic course).
      Seizures typically terminate before adulthood, but a quarter of patients need
      ongoing treatment beyond adolescence. Little is known about their long-term
      seizure and psychosocial outcome. METHODS: Files of 135 outpatients with absence
      epilepsy (76 females; 123 had additional generalised tonic-clonic seizures) were
      retrospectively analysed after a median follow-up of 45.4 years (IQR: 31.9-56.2).
      Eighty-two subjects completed an additional interview. Patients were dichotomised
      according to age at epilepsy onset (childhood: n=82; juvenile: n=53) and course
      of absence seizures (pyknoleptic: n=80; non-pyknoleptic: n=55). RESULTS: Among
      all patients, 53% achieved 5-year terminal seizure remission, 16% without
      antiepileptic medication. Median age at last seizure was lower in patients with
      childhood onset of absence epilepsy (37.7 years) versus juvenile onset (44.4
      years; P<=0.01). However, rates and duration of terminal seizure remission were
      similar. Pyknoleptic versus non-pyknoleptic course of absence seizures made no
      difference for long-term seizure outcome. Multivariate analysis identified only
      higher age at investigation to be associated with terminal 5-year seizure
      remission. Regarding aspects of psychosocial outcome, there were no significant
      differences between the respective subgroups. CONCLUSIONS: These data indicate
      that if absence epilepsy persists beyond adolescence, long-term seizure and
      psychosocial outcome do not differ between childhood and juvenile onset or
      between pyknoleptic and non-pyknoleptic course of absence epilepsy. However,
      higher patient age increases the chance of terminal seizure remission.

PMID- 29348302
TI  - Tracking brain damage in progressive supranuclear palsy: a longitudinal MRI
      study.
AB  - OBJECTIVES: In this prospective, longitudinal, multiparametric MRI study, we
      investigated clinical as well as brain grey matter and white matter (WM) regional
      changes in patients with progressive supranuclear palsy-Richardson's syndrome
      (PSP-RS). METHODS: Twenty-one patients with PSP-RS were evaluated at baseline
      relative to 36 healthy controls and after a mean follow-up of 1.4 years with
      clinical rating scales, neuropsychological tests and MRI scans. RESULTS: Relative
      to controls, patients with PSP-RS showed at baseline a typical pattern of brain
      damage, including midbrain atrophy, frontal cortical thinning and widespread WM
      involvement of the main infratentorial and supratentorial tracts that exceeded
      cortical damage. Longitudinal study showed that PSP-RS exhibited no further
      changes in cortical thinning, which remained relatively focal, while midbrain
      atrophy and WM damage significantly progressed. Corpus callosum and frontal WM
      tract changes correlated with the progression of both disease severity and
      behavioural dysfunction. CONCLUSIONS: This study demonstrated the feasibility of
      carrying out longitudinal diffusion tensor MRI in patients with PSP-RS and its
      sensitivity to identifying the progression of pathology. Longitudinal midbrain
      volume loss and WM changes are associated with PSP disease course.

PMID- 29348304
TI  - miR-20a-5p promotes adipogenic differentiation of murine bone marrow stromal
      cells via targeting Kruppel-like factor 3.
AB  - miR-20a-5p has recently been identified to induce adipogenesis of established
      adipogenic cell lines in our previous study. However, its role and molecular
      mechanisms in the regulation of adipocyte lineage commitment of bone marrow
      derived stromal cells (BMSCs) still need to be explored. In this report, we
      demonstrated the expression of miR-20a-5p was promoted gradually during
      adipogenic differentiation in BMSCs. We also confirmed that miR-20a-5p has a
      positive function in the adipogenic differentiation of BMSCs by gain-of-function
      study with overexpression lentivirus or synthetic mimics of miR-20a-5p, and loss
      of-function study with sponge lentivirus or synthetic inhibitor of miR-20a-5p.
      Dual luciferase reporter assay, GFP repression assay and Western blotting
      suggested Kruppel-like factor 3 (Klf3) was a direct target of miR-20a-5p.
      Furthermore, siRNA-mediated silencing of Klf3 recapitulated the potentiation of
      adipogenesis induced by miR-20a-5p overexpression, whereas enhanced expression of
      Klf3 attenuated the effect of miR-20a-5p. As Klf3 was reported to play an
      inhibitory role in adipogenesis at the initial stage of differentiation, the
      findings we present here indicate that miR-20a-5p promotes adipocyte
      differentiation from BMSCs by targeting and negatively regulating Klf3 in the
      early phase during the procedure of adipogenesis.

PMID- 29348305
TI  - The evolving clinical, genetic and therapeutic landscape of multiple endocrine
      neoplasia type 2.

PMID- 29348306
TI  - Novel targeted therapeutics for MEN2.
AB  - The rearranged during transfection (RET) proto-oncogene was recognized as the
      multiple endocrine neoplasia type 2 (MEN2) causing gene in 1993. Since then, much
      effort has been put into a clear understanding of its oncogenic signaling, its
      biochemical function and ways to block its aberrant activation in MEN2 and
      related cancers. Several small molecules have been designed, developed or
      redirected as RET inhibitors for the treatment of MEN2 and sporadic MTC. However,
      current drugs are mostly active against several other kinases, as they were not
      originally developed for RET. This limits efficacy and poses safety issues.
      Therefore, there is still much to do to improve targeted MEN2 treatments. New,
      more potent and selective molecules, or combinatorial strategies may lead to more
      effective therapies in the near future. Here, we review the rationale for RET
      targeting in MEN2, the use of currently available drugs and novel preclinical and
      clinical RET inhibitor candidates.

PMID- 29348308
TI  - Refining genetic stratification in T-ALL.

PMID- 29348309
TI  - Editing gene engineering to enhance function.

PMID- 29348307
TI  - Non-mammalian models of multiple endocrine neoplasia type 2.
AB  - Twenty-five years ago, RET was identified as the primary driver of multiple
      endocrine neoplasia type 2 (MEN2) syndrome. MEN2 is characterized by several
      transformation events including pheochromocytoma, parathyroid adenoma and,
      especially penetrant, medullary thyroid carcinoma (MTC). Overall, MTC is a rare
      but aggressive type of thyroid cancer for which no effective treatment currently
      exists. Surgery, radiation, radioisotope treatment and chemotherapeutics have all
      shown limited success, and none of these approaches have proven durable in
      advanced disease. Non-mammalian models that incorporate the oncogenic RET
      isoforms associated with MEN2 and other RET-associated diseases have been useful
      in delineating mechanisms underlying disease progression. These models have also
      identified novel targeted therapies as single agents and as combinations. These
      studies highlight the importance of modeling disease in the context of the whole
      animal, accounting for the complex interplay between tumor and normal cells in
      controlling disease progression as well as response to therapy. With convenient
      access to whole genome sequencing data from expanded thyroid cancer patient
      cohorts, non-mammalian models will become more complex, sophisticated and
      continue to complement future mammalian studies. In this review, we explore the
      contributions of non-mammalian models to our understanding of thyroid cancer
      including MTC, with a focus on Danio rerio and Drosophila melanogaster (fish and
      fly) models.

PMID- 29348310
TI  - ASXL1 mutations gain a function.

PMID- 29348311
TI  - Prochemerin processing by factor XIa.

PMID- 29348312
TI  - Composite morphologically and immunohistochemically distinct classical and
      pleomorphic mantle cell lymphomas.

PMID- 29348313
TI  - Sood R, Kamikubo Y, Liu P. Role of RUNX1 in hematological malignancies. Blood.
      2017;129(15):2070-2082.

PMID- 29348315
TI  - Whole-Body Biodistribution and Dosimetry of the Dopamine Transporter Radioligand
      18F-FE-PE2I in Human Subjects.
AB  - 18F-(E)-N-(3-iodoprop-2-enyl)-2beta-carbofluoroethoxy-3beta-(4'-methyl-phenyl)
      nortropane (18F-FE-PE2I) was recently developed and has shown adequate affinity
      and high selectivity for the dopamine transporter (DAT). Previous studies have
      shown promising results for 18F-FE-PE2I as a suitable radioligand for DAT
      imaging. In this study, we investigated the whole-body biodistribution and
      dosimetry of 18F-FE-PE2I in healthy volunteers to support its utility as a
      suitable PET imaging agent for the DAT. Methods: Five healthy volunteers were
      given a mean activity of 2.5 MBq/kg, and 3 PET scans, head to thigh, were
      performed immediately after injection followed by 4 whole-body PET/CT scans
      between 0.5 and 6 h after injection. Blood samples were drawn in connection with
      the whole-body scans, and all urine was collected until 6 h after injection.
      Volumes of interest were delineated around 17 organs on all images, and the areas
      under the time-activity curves were calculated to obtain the total number of
      decays in the organs. The absorbed doses to organs and the effective dose were
      calculated using the software IDAC. Results: The highest activity concentration
      was observed in the liver (0.9%-1.2% injected activity/100 g) up to 30 min after
      injection. At later time points, the highest concentration was seen in the
      gallbladder (1.1%-0.1% injected activity/100 g). The activity excreted with urine
      ranged between 23% and 34%, with a mean of 28%. The urinary bladder received the
      highest absorbed dose (119 MUGy/MBq), followed by the liver (46 MUGy/MBq). The
      effective dose was 23 MUSv/MBq (range, 19-28 MUSv/MBq), resulting in an effective
      dose of 4.6 mSv for an administered activity of 200 MBq. Conclusion: The
      effective dose is within the same order of magnitude as other commonly used PET
      imaging agents as well as DAT agents. The reasonable effective dose, together
      with the previously reported favorable characteristics for DAT imaging and
      quantification, indicates that 18F-FE-PE2I is a suitable radioligand for DAT
      imaging.

PMID- 29348316
TI  - Evaluation of Next-Generation Anti-CD20 Antibodies Labeled with 89Zr in Human
      Lymphoma Xenografts.
AB  - Radioimmunotherapies with monoclonal antibodies to the B-lymphocyte antigen 20
      (CD20) are effective treatments for B-cell lymphomas, but U.S. Food and Drug
      Administration-approved radioimmunotherapies exclusively use radiolabeled murine
      antibodies, potentially limiting redosing. The Food and Drug Administration
      recently approved 2 unlabeled anti-CD20 monoclonal antibodies, obinutuzumab and
      ofatumumab, termed next generation as they are humanized (obinutuzumab) or fully
      human (ofatumumab), thus potentially allowing a greater potential for redosing
      than with previous-generation anti-CD20 antibodies, including rituximab
      (chimeric) and tositumomab (murine), which contain more murine peptide sequences.
      We prepared 89Zr-ofatumumab and 89Zr-obinituzumab and assessed their tumor
      targeting by PET/CT imaging and their biodistribution in a preclinical mouse
      model with CD20 xenografts to determine whether these antibodies have potential
      as theranostics or for radioimmunotherapy. Methods: Obinutuzumab, ofatumumab,
      rituximab, tositumomab, and human IgG (as control) were radiolabeled with 89Zr.
      Raji Burkitt lymphoma xenografts were established in severe combined
      immunodeficient mice. Mice with palpable tumors (n = 4-9) were injected with 89Zr
      obinutuzumab, 89Zr-ofatumumab, 89Zr-rituximab, 89Zr-tositumomab, or 89Zr-IgG,
      with small-animal PET/CT images acquired at 1, 3, and 7 d after injection, and
      then sacrificed for biodistribution analyses. Results: At 1, 3, and 7 d after
      injection, all anti-CD20 antibodies showed clear tumor uptake on PET/CT, with
      minimal tumor uptake of IgG. Biodistribution data showed significantly (P <
      0.005) higher tumor uptake for obinutuzumab (41.4 +/- 7.6 percentage injected
      dose [%ID]/g), ofatumumab (32.6 +/- 17.5 %ID/g), rituximab (28.6 +/- 7.6 %ID/g),
      and tositumomab (28.0 +/- 6.5 %ID/g) than IgG (7.2 +/- 1.2 %ID/g). Tositumomab
      had much higher splenic uptake (186.4 +/- 49.7 %ID/g, P < 0.001) than the other
      antibodies. Conclusion:89Zr-labeled obinutuzumab and ofatumumab localized to
      tumor as well as or better than labeled rituximab and tositumomab, 2 monoclonal
      antibodies that have been used previously in B-cell lymphoma radioimmunotherapy,
      and both obinutuzumab and ofatumumab have the potential for repeated dosing.

PMID- 29348317
TI  - Head-to-Head Comparison of 11C-PBR28 and 18F-GE180 for Quantification of the
      Translocator Protein in the Human Brain.
AB  - 18F-GE180 is a third-generation PET tracer for quantifying the translocator
      protein (TSPO), a biomarker for inflammation. The aim of this study was to
      perform a head-to-head comparison of 18F-GE180 and the well-established TSPO
      tracer 11C-PBR28 by scanning with both tracers during the same day in the same
      subjects. Methods: Five subjects underwent a 90-min PET scan with 11C-PBR28 in
      the morning and 18F-GE180 in the afternoon. A metabolite-corrected arterial input
      function was obtained in each subject for both tracers, and the brain uptake was
      quantified with a 2-tissue-compartment model. Results: The rate of metabolism of
      18F-GE180 in arterial blood was slower than that of 11C-PBR28 (the percentages of
      nonmetabolized parent in plasma at 90 min were 74.9% +/- 4.15% [mean +/- SD] and
      11.2% +/- 1.90%, respectively). The plasma free fractions were similar for both
      tracers: 3.5% +/- 1.1% for 18F-GE180 and 4.1% +/- 1.1% for 11C-PBR28. The average
      total volume of distribution (VT) of 18F-GE180 was about 20 times smaller than
      that of 11C-PBR28 (0.15 +/- 0.03 mL/cm3 for 18F-GE180 and 3.27 +/- 0.66 mL/cm3
      for 11C-PBR28). 18F-GE180 was characterized by poor transfer from the vascular
      compartment to the brain (its plasma-to-tissue rate constant [K1] was about 10
      times smaller than that of 11C-PBR28). Moreover, kinetic modeling was more
      difficult with 18F-GE180, as its VT values were identified with a lower precision
      than those of 11C-PBR28 and outlying values were more frequent. Conclusion: The
      VT of 18F-GE180 was about 20 times smaller than that of 11C-PBR28 because of low
      penetration into the brain from the vascular compartment. In addition, kinetic
      modeling of 18F-GE180 was more challenging than that of 11C-PBR28. Therefore,
      compared with 11C-PBR28, 18F-GE180 had unfavorable characteristics for TSPO
      imaging of the brain.

PMID- 29348318
TI  - Reply: Optimizing Strategies for Immune Checkpoint Imaging with Immuno-PET in
      Preclinical Study.

PMID- 29348319
TI  - Reply: Doxorubicin Effect on Myocardial Metabolism as a Prerequisite for
      Subsequent Development of Cardiac Toxicity: Are There Unsuspected Confounders?

PMID- 29348320
TI  - 18F-FDG PET/CT in Local Ablative Therapies: A Systematic Review.
AB  - Driven by the continuous improvement in the accuracy of cross-sectional imaging,
      image-guided minimally invasive local ablative therapies have received
      incremental interest over the past few years. In this article, we systematically
      review the currently available literature on 18F-FDG PET/CT to monitor the
      efficacy of these local ablative therapies. By including all local ablative
      treatment modalities, tumor types, and organ sites, we provide a comprehensive
      overview of the current status, identify general patterns across studies, and
      provide recommendations for future studies and clinical practice. The Quality
      Assessment of Diagnostic Accuracy Studies (QUADAS) criteria were used to assess
      the quality of the reported diagnostic accuracy of the retrieved studies. Data in
      the literature suggest that 18F-FDG PET/CT is a highly accurate tool to assess
      the technical success of local treatment, to identify residual or recurrent tumor
      early after intervention, and to provide prognostic and predictive information.
      However, prospective interventional studies based on 18F-FDG PET/CT findings of
      disease activity are mandatory to develop uniform and quantitative criteria for
      PET evaluation. Moreover, the optimal timing of 18F-FDG PET/CT after treatment
      may vary according to the location of the disease, with very early imaging being
      possible in solid organs such as the liver but posttreatment imaging being
      challenging for 3 mo in a location such as the lung parenchyma.

PMID- 29348321
TI  - Lower Limbic Metabotropic Glutamate Receptor 5 Availability in Alcohol
      Dependence.
AB  - Animal studies suggest an important role for the metabotropic glutamate receptor
      subtype 5 (mGlu5) in the pathophysiology of alcohol dependence, but direct human
      evidence is lacking. The goal of this study was to investigate cerebral mGlu5
      availability in alcohol-dependent subjects versus controls using 18F-3-fluoro-5
      [(pyridin-3-yl)ethynyl]benzonitrile (18F-FPEB) PET. Methods: Dynamic 90-min 18F
      FPEB scans combined with arterial blood sampling were acquired for 16 recently
      abstinent alcohol-dependent subjects and 32 age-matched controls. Regional mGlu5
      availability was quantified by the 18F-FPEB total distribution volume using both
      a voxel-by-voxel and a volume-of-interest analysis with partial-volume effect
      correction. Alcohol consumption within the last 3 mo was assessed by
      questionnaires and by hair ethyl glucuronide analysis. Craving was assessed using
      the Desire for Alcohol Questionnaire. Results: mGlu5 availability was lower in
      mainly limbic regions of alcohol-dependent subjects than in controls (P < 0.05,
      familywise error-corrected), ranging from 14% in the posterior cingulate cortex
      to 36% in the caudate nucleus. Lower mGlu5 availability was associated with
      higher hair ethyl glucuronide levels for most regions and was related to a lower
      level of craving specifically in the middle frontal gyrus, cingulate cortex, and
      inferolateral temporal lobe. Conclusion: These findings provide human in vivo
      evidence that limbic mGlu5 has a role in the pathophysiology of alcohol
      dependence, possibly involved in a compensatory mechanism helping to reduce
      craving during abstinence.

PMID- 29348322
TI  - Long-Term Risk of Myocardial Infarction Compared to Recurrent Stroke After
      Transient Ischemic Attack and Ischemic Stroke: Systematic Review and Meta
      Analysis.
AB  - BACKGROUND: Uncertainties remain about the current risk of myocardial infarction
      (MI) after ischemic stroke or transient ischemic attack. METHODS AND RESULTS: We
      undertook a systematic review to estimate the long-term risk of MI, compared to
      recurrent stroke, with temporal trends in ischemic stroke/transient ischemic
      attack patients. Annual risks and 95% confidence intervals (95% CI) of MI and
      recurrent stroke were estimated using random-effect meta-analyses. We calculated
      incidence ratios of MI/recurrent stroke, for fatal and nonfatal events, using
      similar analyses. Rate ratios for MI in patients with potential risk factors
      compared to those without were calculated using Poisson regression.A total of 58
      studies (131 299 patients) with a mean (range) follow-up of 3.5 (1.0-10.0) years
      were included. The risk of MI was 1.67%/y (95% CI 1.36-1.98, Phet<0.001 for
      heterogeneity) and decreased over time (Pint=0.021); 96% of the heterogeneity
      between studies was explained by study design, study period, follow-up duration,
      mean age, proportion of patients on antithrombotic therapy, and incident versus
      combined ischemic stroke/transient ischemic attack. The risk of recurrent stroke
      was 4.26%/y (95% CI 3.43-5.09, Phet<0.001), with no change over time (Pint=0.63).
      The risk of fatal MI was half the risk of recurrent strokes ending in fatality
      (incidence ratio=0.51, 95% CI 0.14-0.89, Phet=0.58). The risk of nonfatal MI was
      75% smaller than the risk of recurrent nonfatal stroke (incidence ratio=0.25,
      95%CI 0.02-0.50, Phet=0.68). Male sex, hypertension, coronary and peripheral
      artery diseases were associated with a doubled risk of MI. CONCLUSIONS: After
      ischemic stroke/transient ischemic attack, the risk of MI is currently <2%/y, and
      recurrent stroke is a more common cause of death than MI.

PMID- 29348323
TI  - Epothilone B Benefits Nigrostriatal Pathway Recovery by Promoting Microtubule
      Stabilization After Intracerebral Hemorrhage.
AB  - BACKGROUND: Many previous clinical studies have demonstrated that the
      nigrostriatal pathway, which plays a vital role in movement adjustment, is
      significantly impaired after stroke, according to medical imaging and autopsies.
      However, the basic pathomorphological changes have been poorly investigated to
      date. This study was designed to explore the pathomorphological changes,
      mechanism, and therapeutic method of nigrostriatal impairment after intracerebral
      hemorrhage (ICH). METHODS AND RESULTS: Intrastriatal injection of autologous
      blood or microtubule depolymerization reagent nocodazole was performed to mimic
      the pathology of ICH in C57/BL6 mice. Immunofluorescence, Western blotting,
      electron microscopy, functional behavioral tests, and anterograde and retrograde
      neural circuit tracking techniques were used in these mice. The data showed that
      the number of dopamine neurons and the dopamine concentration were severely
      decreased and that fine motor function was impaired after ICH. Microtubule
      depolymerization was the main contributor to the loss of dopamine neurons and to
      motor function deficits after ICH, as was also proven by intrastriatal injection
      of nocodazole. Moreover, administration of the microtubule stabilizer epothilone
      B (1.5 mg/kg) improved the integrity of the nigrostriatal pathway neural circuit,
      increased the number of dopamine neurons (4598+/-896 versus 3125+/-355; P=0.034)
      and the dopamine concentration (4.28+/-0.99 versus 3.08+/-0.75 ng/mg; P=0.041),
      and enhanced fine motor functional recovery associated with increased acetylated
      alpha-tubulin expression to maintain microtubule stabilization after ICH.
      CONCLUSIONS: Our results clarified the pathomorphological changes of the
      nigrostriatal pathway after ICH and found that epothilone B helped alleviate
      nigrostriatal pathway injury after ICH, associated with promoting alpha-tubulin
      acetylation to maintain microtubule stabilization, thus facilitating motor
      recovery.

PMID- 29348325
TI  - Low-Level, Global Transcription during Mitosis and Dynamic Gene Reactivation
      during Mitotic Exit.
AB  - Mitosis is thought to be a period of transcriptional silence due to the compact
      nature of mitotic chromosomes and the apparent exclusion of RNA Pol II and many
      transcription factors from mitotic chromatin. Yet accurate reactivation of a
      cell's specific gene expression program is needed to reestablish functional cell
      identity after mitosis. The majority of studies on protein regulation and
      localization during mitosis have relied extensively on antibodies and cross
      linking-based approaches that are known to artifactually exclude proteins from
      mitotic chromatin. Here we show that RNA Pol II localization in mitosis is
      antibody- and fixation-dependent, and that direct assessment of transcription by
      pulse-labeling nascent RNA reveals global, low-level mitotic transcription. We
      also find a hierarchy of gene reactivation as the cells transition from mitosis
      to their interphase amplitude of gene expression. Resetting of gene transcription
      during mitotic exit is coincident with enhancer transcription. Our work thus
      shifts focus from assessing mitotic exit as a binary transcription switch to a
      more nuanced concert of transcription amplitude and enhancer usage. We suggest
      that understanding how gene expression patterns are conserved during mitosis
      rests upon deciphering how transcription is maintained by promoters.

PMID- 29348324
TI  - PlexinD1 signaling controls morphological changes and migration termination in
      newborn neurons.
AB  - Newborn neurons maintain a very simple, bipolar shape, while they migrate from
      their birthplace toward their destinations in the brain, where they differentiate
      into mature neurons with complex dendritic morphologies. Here, we report a
      mechanism by which the termination of neuronal migration is maintained in the
      postnatal olfactory bulb (OB). During neuronal deceleration in the OB, newborn
      neurons transiently extend a protrusion from the proximal part of their leading
      process in the resting phase, which we refer to as a filopodium-like lateral
      protrusion (FLP). The FLP formation is induced by PlexinD1 downregulation and
      local Rac1 activation, which coincide with microtubule reorganization and the
      pausing of somal translocation. The somal translocation of resting neurons is
      suppressed by microtubule polymerization within the FLP The timing of neuronal
      migration termination, controlled by Sema3E-PlexinD1-Rac1 signaling, influences
      the final positioning, dendritic patterns, and functions of the neurons in the OB
      These results suggest that PlexinD1 signaling controls FLP formation and the
      termination of neuronal migration through a precise control of microtubule
      dynamics.

PMID- 29348327
TI  - Genome Instability as a Consequence of Defects in the Resolution of Recombination
      Intermediates.
AB  - The efficient processing of homologous recombination (HR) intermediates, which
      often contain four-way structures known as Holliday junctions (HJs), is required
      for proper chromosome segregation at mitosis. Eukaryotic cells possess three
      distinct pathways of resolution: (i) HJ dissolution mediated by BLM-topoisomerase
      IIIalpha-RMI1-RMI2 (BTR) complex, and HJ resolution catalyzed by either (ii) SLX1
      SLX4-MUS81-EME1-XPF-ERCC1 (SMX complex) or (iii) GEN1. The BTR pathway acts at
      all times throughout the cell cycle, whereas the actions of SMX and GEN1 are
      restrained in S phase and become elevated late in the cell cycle to ensure the
      resolution of persistent recombination intermediates before mitotic division. By
      developing a "resolvase-deficient" model system in which the activities of MUS81
      and GEN1 are compromised, we have explored the fate of unresolved recombination
      intermediates. We find that covalently linked sister chromatids promote the
      formation of a new class of ultrafine bridges at anaphase that we term HR-UFBs.
      These bridges are broken at cell division, leading to activation of the DNA
      damage checkpoint and repair by nonhomologous end joining (NHEJ) in the next cell
      cycle. As a consequence, high levels of gross chromosomal rearrangements and
      aberrations are observed, together with frequent cell death. These results show
      that the HJ resolvases provide essential functions for the resolution of
      recombination intermediates, even in cells that remain proficient for BTR
      mediated HJ dissolution.

PMID- 29348326
TI  - Symmetry from Asymmetry or Asymmetry from Symmetry?
AB  - The processes of DNA replication and mitosis allow the genetic information of a
      cell to be copied and transferred reliably to its daughter cells. However, if DNA
      replication and cell division were always performed in a symmetric manner, the
      result would be a cluster of tumor cells instead of a multicellular organism.
      Therefore, gaining a complete understanding of any complex living organism
      depends on learning how cells become different while faithfully maintaining the
      same genetic material. It is well recognized that the distinct epigenetic
      information contained in each cell type defines its unique gene expression
      program. Nevertheless, how epigenetic information contained in the parental cell
      is either maintained or changed in the daughter cells remains largely unknown.
      During the asymmetric cell division (ACD) of Drosophila male germline stem cells,
      our previous work revealed that preexisting histones are selectively retained in
      the renewed stem cell daughter, whereas newly synthesized histones are enriched
      in the differentiating daughter cell. We also found that randomized inheritance
      of preexisting histones versus newly synthesized histones results in both stem
      cell loss and progenitor germ cell tumor phenotypes, suggesting that programmed
      histone inheritance is a key epigenetic player for cells to either remember or
      reset cell fates. Here, we will discuss these findings in the context of current
      knowledge on DNA replication, polarized mitotic machinery, and ACD for both
      animal development and tissue homeostasis. We will also speculate on some
      potential mechanisms underlying asymmetric histone inheritance, which may be used
      in other biological events to achieve the asymmetric cell fates.

PMID- 29348328
TI  - Correction for Johnson et al., "Complete Genome Sequences for 35 Biothreat Assay
      Relevant Bacillus Species".

PMID- 29348329
TI  - Draft Genome Sequences of 510 Listeria monocytogenes Strains from Food Isolates
      and Human Listeriosis Cases from Northern Italy.
AB  - Listeriosis outbreaks are frequently multistate/multicountry outbreaks,
      underlining the importance of molecular typing data for several diverse and well
      characterized isolates. Large-scale whole-genome sequencing studies on Listeria
      monocytogenes isolates from non-U.S. locations have been limited. Herein, we
      describe the draft genome sequences of 510 L. monocytogenes isolates from
      northern Italy from different sources.

PMID- 29348330
TI  - Complete Genome Sequence of Escherichia coli Bacteriophage PGT2.
AB  - Bacteriophage PGT2 was isolated from horse feces by using an uncharacterized
      Escherichia coli strain, 7s, isolated from the same sample as the host.
      Bacteriophage PGT2 and a related phage, phiKT, which was previously isolated from
      the same source, are likely to represent a new genus within the Autographivirinae
      subfamily of the Podoviridae family of viruses.

PMID- 29348331
TI  - Draft Genome Sequences of Two Vibrio parahaemolyticus Strains Associated with
      Gastroenteritis after Raw Seafood Ingestion in Colorado.
AB  - Vibrio parahaemolyticus is a Gram-negative pathogen associated with
      gastrointestinal and wound infections after exposure to raw seafood or
      contaminated waters. We report here the whole-genome sequences of two stool
      isolates (CDC-AM50933 and CDC-AM43539) from patients in Colorado presenting with
      gastroenteritis after ingesting raw seafood.

PMID- 29348332
TI  - Draft Genome Sequence of Mycobacterium setense CSUR47.
AB  - Mycobacterium setense CSUR47 is a rapidly growing Mycobacterium species strain
      isolated from pus collected from a left maxillary sinus in Marseille, France.
      Here, we report the complete 6,278,097-bp genome sequence of M. setense CSUR47,
      which exhibits a 66.40% GC content and encodes 5,863 protein-coding genes, 48
      tRNAs, and 9 rRNAs.

PMID- 29348333
TI  - Draft Genome Sequence and Annotation of the Obligate Bacterial Endosymbiont
      Caedibacter taeniospiralis, Causative Agent of the Killer Phenotype in Paramecium
      tetraurelia.
AB  - Caedibacter taeniospiralis is an obligate endosymbiont living in the cytoplasm of
      Paramecium tetraureliaC. taeniospiralis causes the so-called killer trait,
      eliminating intraspecific competitors of its host when released into the medium
      by the concerted action of the unusual protein structure R-body (refractile body)
      in addition to an as-yet-unknown toxin.

PMID- 29348334
TI  - Draft Genome Sequences of Phenotypically Distinct Janthinobacterium sp. Isolates
      Cultured from the Hudson Valley Watershed.
AB  - Investigation of the Hudson Valley watershed reveals many violacein-producing
      bacteria. These are of interest for their biotherapeutic potential in treating
      chytrid infections of amphibians. The draft whole-genome sequences for seven
      Janthinobacterium isolates with a variety of phenotypes are provided in this
      study.

PMID- 29348335
TI  - Complete Genome Sequence of the African Green Monkey Simian Foamy Virus Serotype
      3 Strain FV2014 (SFVcae_FV2014).
AB  - The full-length sequence of simian foamy virus serotype 3 (SFV-3) strain FV2014,
      an African green monkey (Chlorocebus aethiops) isolate, was obtained using high
      throughput sequencing. SFVcae_FV2014 consisted of 13,127 bp and had a genomic
      organization similar to those of other SFVs but was distinct from SFV strain LK3,
      isolated from the same monkey species.

PMID- 29348336
TI  - Nine Whole-Genome Assemblies of Yersinia pestis subsp. microtus bv. Altaica
      Strains Isolated from the Altai Mountain Natural Plague Focus (No. 36) in Russia.
AB  - We report here the draft genome sequences of nine Yersinia pestis subsp. microtus
      bv. Altaica strains isolated from the Altai Mountain plague focus (no. 36), which
      represent the 0.PE4 phylogroup circulating in populations of Mongolian pika
      (Ochotona pallasi).

PMID- 29348337
TI  - Complete Genome Sequence of Sphingorhabdus sp. YGSMI21, Exhibiting High
      Enantioselective Epoxide Hydrolase Activity.
AB  - Sphingorhabdus sp. YGSMI21 is a novel strain exhibiting high enantioselective
      hydrolysis activity for styrene oxide. Here, we present its complete genome
      sequence, consisting of one circular chromosome (3.86 Mb) and one plasmid (0.196
      Mb).

PMID- 29348338
TI  - Draft Genome Sequence of a Novel Bacterium, Pseudomonas sp. Strain MR 02, Capable
      of Pyomelanin Production, Isolated from the Mahananda River at Siliguri, West
      Bengal, India.
AB  - The draft genome sequence of a novel strain, Pseudomonas sp. MR 02, a pyomelanin
      producing bacterium isolated from the Mahananda River at Siliguri, West Bengal,
      India, is reported here. This strain has a genome size of 5.94 Mb, with an
      overall G+C content of 62.6%. The draft genome reports 5,799 genes (mean gene
      length, 923 bp), among which 5,503 are protein-coding genes, including the genes
      required for the catabolism of tyrosine or phenylalanine for the characteristic
      production of homogentisic acid (HGA). Excess HGA, on excretion, auto-oxidizes
      and polymerizes to form pyomelanin.

PMID- 29348339
TI  - Draft Genome Sequences of Strains TRE 1, TRE D, TRE H, and TRI 7, Isolated from
      Tamarins and Belonging to Four Putative Novel Bifidobacterium Species.
AB  - Bifidobacterium sp. strains TRE 1, TRE D, TRE H, and TRI 7 were isolated from two
      tamarins housed in Parco Natura Viva, Garda Zoological Park S.r.l. (Bussolengo,
      Verona, Italy). These strains belong to four putative novel species of the genus
      Bifidobacterium The genome sizes were 2.7 Mb for TRE 1, 2.7 Mb for TRE D, 2.4 Mb
      for TRE H, and 2.7 Mb for TRI 7. The average GC contents were 63.18% for TRE 1,
      58.27% for TRE D, 57.11% for TRE H, and 63.79% for TRI 7.

PMID- 29348340
TI  - Complete Genome Sequence of Bacillus methylotrophicus Strain NKG-1, Isolated from
      the Changbai Mountains, China.
AB  - We report here the complete genome sequence of Bacillus methylotrophicus NKG-1,
      isolated from rare dormant volcanic soils on the Changbai Mountains in China. The
      4.20-Mb genome contains 4,432 genes and has a G+C content of 47.06%.

PMID- 29348341
TI  - Draft Genome Sequence of Escherichia coli Strain SN137, a Bacterium with
      Extracellular Proteolytic Activity on Immunoglobulins and Persistence in Human
      Tissue Blood.
AB  - The draft genome sequence of Escherichia coli strain SN137 is reported here. The
      genome comprises 172 contigs, corresponding to 4.9 Mb with 50% G+C content, and
      contains several genes related to pathogenicity that explain its survival in
      human hematic tissue.

PMID- 29348342
TI  - Draft Genome Sequence of the Crude Oil-Degrading and Biosurfactant-Producing
      Strain Cobetia sp. QF-1.
AB  - We report here the draft genome of Cobetia sp. QF-1, a cold-adapted bacterium
      isolated from crude oil-contaminated seawater of the Yellow Sea, China. This
      genome is approximately 4.1 Mb (G+C content, 57.44%) with 3,513 protein-coding
      sequences. Cobetia sp. QF-1 shows crude oil degradation and biosurfactant
      production activity at low temperature.

PMID- 29348343
TI  - Draft Genome Sequence of Coxiella burnetii Historical Strain Leningrad-2,
      Isolated from Blood of a Patient with Acute Q Fever in Saint Petersburg, Russia.
AB  - This is the announcement of a draft genome sequence of Coxiella burnetii strain
      Leningrad-2, phase I. The strain, which is mildly virulent in infected guinea
      pigs, was isolated in 1957 from the blood of a patient with acute Q fever in
      Leningrad (now Saint Petersburg), Russia.

PMID- 29348345
TI  - Draft Genome Sequence of Vibrio parahaemolyticus Strain M1-1, Which Causes Acute
      Hepatopancreatic Necrosis Disease in Shrimp in Vietnam.
AB  - We report here the genome sequence of Vibrio parahaemolyticus strain M1-1, which
      causes a mild form of shrimp acute hepatopancreatic necrosis disease (AHPND).
      Compared to other virulent strains, the M1-1 genome appeared to express several
      additional genes, while some genes were missing. These instabilities may be
      related to the reduced virulence of M1-1.

PMID- 29348344
TI  - Draft Genome Sequence of Bacillus velezensis OSY-S3, a Producer of Potent
      Antimicrobial Agents Active against Bacteria and Fungi.
AB  - Bacillus velezensis OSY-S3 produces anti-Listeria, anti-Escherichia coli, and
      antifungal compounds. Additionally, fermentate of B. velezensis OSY-S3 culture
      removes Staphylococcus aureus biofilms effectively. The draft genome sequence of
      B. velezensis OSY-S3 reported here had a genome size of ~3.90 Mb and a G+C
      content of 46.5%.

PMID- 29348346
TI  - Draft Genome Sequence of Streptococcus canis Clinical Strain TA4, Harboring the M
      Like Protein Gene and Isolated in Japan from a Patient with Bacteremia.
AB  - Streptococcus canis is an animal-origin beta-hemolytic bacterium that can cause
      severe infections in animals and occasionally infects humans. Here, we report a
      draft genome sequence of an S. canis strain harboring the M-like protein gene.
      This strain was isolated from a patient with bacteremia (reported by Taniyama et
      al. [D. Taniyama, Y. Abe, T. Sakai, T. Kikuchi, and T. Takahashi, IDCases 7:48
      52, 2017, https://doi.org/10.1016/j.idcr.2017.01.002]). The draft genome
      comprises 2,129,080 bp in 60 contigs.

PMID- 29348347
TI  - Completed Genome Sequences of Strains from 36 Serotypes of Salmonella.
AB  - We report here the completed closed genome sequences of strains representing 36
      serotypes of Salmonella These genome sequences will provide useful references for
      understanding the genetic variation between serotypes, particularly as references
      for mapping of raw reads or to create assemblies of higher quality, as well as to
      aid in studies of comparative genomics of Salmonella.

PMID- 29348348
TI  - Whole-Genome Sequence of a Mycobacterium goodii Isolate from a Pediatric Patient
      in South Africa.
AB  - We describe here the draft genome sequence of a Mycobacterium goodii isolate from
      a pediatric patient in Western Cape, South Africa. To our knowledge, this is the
      second reported genome of this rapidly growing nontuberculous mycobacterial
      species.

PMID- 29348349
TI  - Complete Genome Sequence of Streptomyces Bacteriophage Abt2graduatex2.
AB  - The Streptomyces bacteriophage Abt2graduatex2 is a double-stranded DNA (dsDNA)
      Siphoviridae isolated from soil collected in Baltimore, MD, and harvested using
      Streptomyces griseus subsp. griseus Abt2graduatex2, a cluster BG phage, encodes
      an HicA-like toxin.

PMID- 29348350
TI  - Draft Genome Sequences of 14 Strains of Pseudomonas Isolated from Prunus sp.
      Plants.
AB  - We present here the draft genome sequences of 14 Pseudomonas strains isolated
      from Prunus sp. plants in New Zealand and overseas. These new genomic data will
      be used to improve the detection of Pseudomonas strains found in imported plant
      material at the New Zealand border, improving the time involved in the process of
      biosecurity decision-making.

PMID- 29348351
TI  - Complete Genome Sequence of the Halophilic Methylotrophic Methanogen Archaeon
      Methanohalophilus portucalensis Strain FDF-1T.
AB  - We report here the complete genome sequence (2.08 Mb) of Methanohalophilus
      portucalensis strain FDF-1T, a halophilic methylotrophic methanogen isolated from
      the sediment of a saltern in Figeria da Foz, Portugal. The average nucleotide
      identity and DNA-DNA hybridization analyses show that Methanohalophilus mahii, M.
      halophilus, and M. portucalensis are three different species within the
      Methanosarcinaceae family.

PMID- 29348352
TI  - Complete Genome Sequence of Lacinutrix venerupis DOK2-8 Isolated from Marine
      Sediment from the East Sea, Republic of Korea.
AB  - Lacinutrix venerupis has recently been considered a potential fish pathogen.
      Here, we report the complete genome sequence of L. venerupis DOK2-8, which
      possesses several virulence-related genes. This strain may be potentially
      virulent to other marine organisms, and its genomic information will provide
      important insights into the biodiversity of the genus Lacinutrix.

PMID- 29348353
TI  - Next-Generation Sequencing Reveals the First Complete Genome Sequence of Cowpea
      aphid-borne mosaic virus from Uganda.
AB  - We present here the first complete genome sequence of Cowpea aphid-borne mosaic
      virus (CABMV) isolated from cowpea in Uganda and compare it with five CABMV
      complete genome sequences from Brazil (2), India (2), and Zimbabwe (1). It most
      resembled the genomes of two Brazilian isolates (MG-Avr and BR1) and one Indian
      isolate (RR3).

PMID- 29348354
TI  - Genome Sequence of Enterococcus mundtii EM01, Isolated from Bombyx mori Midgut
      and Responsible for Flacherie Disease in Silkworms Reared on an Artificial Diet.
AB  - The whole genome sequence of Enterococcus mundtii strain EM01 is reported here.
      The isolate proved to be the cause of flacherie in Bombyx mori To date, the
      genomes of 11 other E. mundtii strains have been sequenced. EM01 is the only
      strain that displayed active pathological effects on its associated animal
      species.

PMID- 29348355
TI  - Genome Sequence of Trypanosoma cruzi Strain Bug2148.
AB  - Trypanosoma cruzi belongs to the group of mitochondrion-containing eukaryotes and
      has a highly plastic genome, unusual gene organization, and complex mechanisms
      for gene expression (polycistronic transcription). We report here the genome
      sequence of strain Bug2148, the first genomic sequence belonging to cluster TcV,
      which has been related to vertical transmission.

PMID- 29348356
TI  - Draft Genome Sequence of Fusarium fujikuroi, a Fungus Adapted to the Fuel
      Environment.
AB  - Fusarium fujikuroi isolate FUS01 is highly adapted to grow in jet fuel with
      predicted genes involved in hydrocarbon catabolism and carbon assimilation. The
      draft genome size is estimated at 49 Mb containing 18,578 proteins with high
      similarity to that of F. fujikuroi isolate B14.

PMID- 29348357
TI  - Draft Genome Sequence of Bacillus subtilis 2C-9B, a Strain with Biocontrol
      Potential against Chili Pepper Root Pathogens and Tolerance to Pb and Zn.
AB  - Bacillus subtilis 2C-9B, obtained from the rhizosphere of wild grass, exhibits
      inhibition against root rot causal pathogens in Capsicum annuum, Pb and Zn
      tolerance, and plant growth promotion in medium supplemented with Pb. The genome
      of B. subtilis 2C-9B was sequenced and the draft genome assembled, with a length
      of 4,215,855 bp and 4,723 coding genes.

PMID- 29348358
TI  - Complete Genome Sequence of Kyrpidia sp. Strain EA-1, a Thermophilic Knallgas
      Bacterium, Isolated from the Azores.
AB  - Kyrpidia sp. strain EA-1 is a thermophilic hydrogen-oxidizing bacterium isolated
      from hydrothermal systems at Sao Miguel Island, Portugal. Here, we present the
      complete genome sequence of the strain assembled to a single circular chromosome.
      The genome spans 3,352,175 bp, with a GC content of 58.7%.

PMID- 29348359
TI  - Complete Genome Sequence of the Type Strain of Macrococcus canis.
AB  - The first complete genome sequence of the recently described Macrococcus canis
      species has been determined for the strain KM45013T (=DSM 101690T = CCOS 969T =
      CCUG 68920T = CCM 8748T). The strain was isolated from a dog with rhinitis and
      contains a putative gamma-hemolysin and a mecB-carrying staphylococcal cassette
      chromosome mec element (SCCmecKM45013).

PMID- 29348360
TI  - Complete Genome Sequences of Three Moraxella osloensis Strains Isolated from
      Human Skin.
AB  - Here, we present the complete whole-genome sequences of three Moraxella osloensis
      strains with octylphenol polyethoxylate-degrading abilities. These strains were
      isolated from human skin.

PMID- 29348361
TI  - Complete Genome Sequence of Paracoccus yeei TT13, Isolated from Human Skin.
AB  - Paracoccus yeei TT13 was isolated from human skin because of its ability to
      degrade propylene glycol. Here, we present the whole-genome sequence of this
      strain; it possesses one 3.58-Mb chromosome and six plasmids. TT13 genome
      analysis indicated that this bacterium has denitrification potential.

PMID- 29348362
TI  - Draft Genome Sequence of a Multistress-Tolerant Yeast, Pichia kudriavzevii NG7.
AB  - Pichia kudriavzevii NG7 is a multistress-tolerant yeast, isolated from grape
      skins. Here, we report the draft genome sequence of P. kudriavzevii NG7, to
      understand its biochemical regulation and metabolic pathways.

PMID- 29348363
TI  - Atomic-resolution transmission electron microscopy of electron beam-sensitive
      crystalline materials.
AB  - High-resolution imaging of electron beam-sensitive materials is one of the most
      difficult applications of transmission electron microscopy (TEM). The challenges
      are manifold, including the acquisition of images with extremely low beam doses,
      the time-constrained search for crystal zone axes, the precise image alignment,
      and the accurate determination of the defocus value. We develop a suite of
      methods to fulfill these requirements and acquire atomic-resolution TEM images of
      several metal organic frameworks that are generally recognized as highly
      sensitive to electron beams. The high image resolution allows us to identify
      individual metal atomic columns, various types of surface termination, and
      benzene rings in the organic linkers. We also apply our methods to other electron
      beam-sensitive materials, including the organic-inorganic hybrid perovskite
      CH3NH3PbBr3.

PMID- 29348364
TI  - Building superlattices from individual nanoparticles via template-confined DNA
      mediated assembly.
AB  - DNA programmable assembly has been combined with top-down lithography to
      construct superlattices of discrete, reconfigurable nanoparticle architectures on
      a gold surface over large areas. Specifically, the assembly of individual
      colloidal plasmonic nanoparticles with different shapes and sizes is controlled
      by oligonucleotides containing "locked" nucleic acids and confined environments
      provided by polymer pores to yield oriented architectures that feature tunable
      arrangements and independently controllable distances at both nanometer- and
      micrometer-length scales. These structures, which would be difficult to construct
      by other common assembly methods, provide a platform to systematically study and
      control light-matter interactions in nanoparticle-based optical materials. The
      generality and potential of this approach are explored by identifying a broadband
      absorber with a solvent polarity response that allows dynamic tuning of visible
      light absorption.

PMID- 29348366
TI  - Structures of human PRC2 with its cofactors AEBP2 and JARID2.
AB  - Transcriptionally repressive histone H3 lysine 27 methylation by Polycomb
      repressive complex 2 (PRC2) is essential for cellular differentiation and
      development. Here we report cryo-electron microscopy structures of human PRC2 in
      a basal state and two distinct active states while in complex with its cofactors
      JARID2 and AEBP2. Both cofactors mimic the binding of histone H3 tails. JARID2,
      methylated by PRC2, mimics a methylated H3 tail to stimulate PRC2 activity,
      whereas AEBP2 interacts with the RBAP48 subunit, mimicking an unmodified H3 tail.
      SUZ12 interacts with all other subunits within the assembly and thus contributes
      to the stability of the complex. Our analysis defines the complete architecture
      of a functionally relevant PRC2 and provides a structural framework to understand
      its regulation by cofactors, histone tails, and RNA.

PMID- 29348365
TI  - Detection and localization of surgically resectable cancers with a multi-analyte
      blood test.
AB  - Earlier detection is key to reducing cancer deaths. Here, we describe a blood
      test that can detect eight common cancer types through assessment of the levels
      of circulating proteins and mutations in cell-free DNA. We applied this test,
      called CancerSEEK, to 1005 patients with nonmetastatic, clinically detected
      cancers of the ovary, liver, stomach, pancreas, esophagus, colorectum, lung, or
      breast. CancerSEEK tests were positive in a median of 70% of the eight cancer
      types. The sensitivities ranged from 69 to 98% for the detection of five cancer
      types (ovary, liver, stomach, pancreas, and esophagus) for which there are no
      screening tests available for average-risk individuals. The specificity of
      CancerSEEK was greater than 99%: only 7 of 812 healthy controls scored positive.
      In addition, CancerSEEK localized the cancer to a small number of anatomic sites
      in a median of 83% of the patients.

PMID- 29348369
TI  - [History of Researches on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome].
AB  - Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disease
      characterized by chronic, profound, disabling, and unexplained fatigue. The first
      patient with ME/CFS in Japan was identified and described in 1990 by Prof. Teruo
      Kitani and Dr. Hirohiko Kuratsune of the Research Institute for Microbial
      Diseases, Osaka University. Since then, a variety of studies have been performed
      to determine the objective biomarkers of the disease. Although it is hypothesized
      that brain inflammation is involved in the pathophysiology of ME/CFS, there is to
      date no direct evidence of neuroinflammation in patients with ME/CFS. Our recent
      positron emission tomography study successfully demonstrated that microglial
      activation, which is linked to neuroinflammation, occurs in widespread brain
      areas in patients with ME/CFS, and is associated with the severity of the
      neuropsychological symptoms. Thus, evaluation of neuroinflammation in patients
      with ME/CFS may be essential for understanding the core pathophysiology of the
      disease, and for developing objective diagnostic criteria and effective medical
      treatments for ME/CFS. Here, we describe disease-related pathophysiological
      findings and topics, and discuss the history of the diagnostic and therapeutic
      attempts based on previous findings in Japan.

PMID- 29348368
TI  - Defining the physiological role of SRP in protein-targeting efficiency and
      specificity.
AB  - The signal recognition particle (SRP) enables cotranslational delivery of
      proteins for translocation into the endoplasmic reticulum (ER), but its full in
      vivo role remains incompletely explored. We combined rapid auxin-induced SRP
      degradation with proximity-specific ribosome profiling to define SRP's in vivo
      function in yeast. Despite the classic view that SRP recognizes amino-terminal
      signal sequences, we show that SRP was generally essential for targeting
      transmembrane domains regardless of their position relative to the amino
      terminus. By contrast, many proteins containing cleavable amino-terminal signal
      peptides were efficiently cotranslationally targeted in SRP's absence. We also
      reveal an unanticipated consequence of SRP loss: Transcripts normally targeted to
      the ER were mistargeted to mitochondria, leading to mitochondrial defects. These
      results elucidate SRP's essential roles in maintaining the efficiency and
      specificity of protein targeting.

PMID- 29348367
TI  - A pathway for mitotic chromosome formation.
AB  - Mitotic chromosomes fold as compact arrays of chromatin loops. To identify the
      pathway of mitotic chromosome formation, we combined imaging and Hi-C analysis of
      synchronous DT40 cell cultures with polymer simulations. Here we show that in
      prophase, the interphase organization is rapidly lost in a condensin-dependent
      manner, and arrays of consecutive 60-kilobase (kb) loops are formed. During
      prometaphase, ~80-kb inner loops are nested within ~400-kb outer loops. The loop
      array acquires a helical arrangement with consecutive loops emanating from a
      central "spiral staircase" condensin scaffold. The size of helical turns
      progressively increases to ~12 megabases during prometaphase. Acute depletion of
      condensin I or II shows that nested loops form by differential action of the two
      condensins, whereas condensin II is required for helical winding.

PMID- 29348370
TI  - [Diagnosis and Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome].
AB  - We present here the Japanese clinical diagnostic criteria for myalgic
      encephalomyelitis/chronic fatigue syndrome (ME/CFS) that were proposed in 2016 by
      the Japanese Ministry of Health, Labour and Welfare study group. The clinical
      diagnosis criteria of ME/CFS were created to be used by healthcare agencies in
      charge of primary care practice. We also explain the current prognosis in ME/CFS
      and medical treatments used in major medical institutions in Japan.

PMID- 29348371
TI  - [Neuroinflammation in the Brain of Patients with Myalgic
      Encephalomyelitis/Chronic Fatigue Syndrome].
AB  - Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by
      chronic, profound, disabling, and unexplained fatigue; cognitive impairment; and
      chronic widespread pain. By using positron emission tomography, our study
      demonstrated neuroinflammation in the brain of patients with ME/CFS.
      Neuroinflammation was found to be widespread in the brain areas of the patients
      with ME/CFS and was associated with the severity of their neuropsychological
      symptoms. The ongoing research would lead to the establishment of objective
      diagnostic criteria and development of an appropriate therapy.

PMID- 29348372
TI  - [New Diagnostic Biomarkers for Chronic Fatigue Syndrome].
AB  - Chronic fatigue syndrome (CFS) is a persistent and unexplained pathological state
      characterized by exertional and severely debilitating fatigue, with/without
      symptoms of infection or neuropsychiatric symptoms, and with a minimum duration
      of 6 consecutive months. The pathogenesis of CFS is not fully understood. There
      are no firmly established diagnostic biomarkers or treatment, due to incomplete
      understanding of the etiology of CFS and diagnostic uncertainty. We performed
      comprehensive metabolomic analyses of blood samples obtained from patients with
      CFS and healthy controls to establish an objective diagnosis of CFS. Here, we
      review previous findings concerning the immune, endocrine, and metabolic system
      in animal models for CFS and the patients, and present our results which may
      contribute to the development of a diagnostic biomarker for CFS.

PMID- 29348373
TI  - [Immunopathogenesis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
      (ME/CFS)].
AB  - A recent study on the pathogenesis of myalgic encephalomyelitis/chronic fatigue
      syndrome (ME/CFS) has revealed an elevation of inflammatory and anti-inflammatory
      cytokines in the sera and cerebrospinal fluids of the patients and presence of
      autoantibodies in subgroups of ME/CFS patients. Furthermore, investigator
      initiated clinical trials have proved the efficacy of anti-CD20 antibody
      (rituximab), that eliminate B cells, in the treatment of ME/CFS. Based on these
      findings, we hypothesize that immune abnormalities, such as enhanced autoimmune
      responses, may play an essential role in the neuroinflammatory pathogenesis of
      ME/CFS.

PMID- 29348374
TI  - [Neurologic Abnormalities in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome:
      A Review].
AB  - Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is an illness
      characterized by fatigue lasting for at least six months, post-exertional
      malaise, unrefreshing sleep, cognitive impairment and orthostatic intolerance.
      ME/CFS has been a controversial illness because it is defined exclusively by
      subjective complaints. However, recent studies of neuroimaging as well as
      analysis of blood markers, energy metabolism and mitochondrial function have
      revealed many objective biological abnormalities. Specifically, it is suspected
      that the symptoms of ME/CFS may be triggered by immune activation - either inside
      or outside the brain - through release of inflammatory cytokines. In this review,
      we summarize potentially important recent findings on ME/CFS, focusing on
      objective evidence.

PMID- 29348375
TI  - [Suspected Non-Alzheimer's Disease Pathophysiology (SNAP) and Its Pathological
      Backgrounds in the Diagnosis of Preclinical and Clinical Alzheimer's Disease].
AB  - Suspected non-Alzheimer's disease pathophysiology (SNAP) is a biomarker-based
      condition that is found in individuals with normal levels of amyloid-beta protein
      (Abeta) markers (A-) and abnormal levels of markers of neurodegeneration or
      neuronal injury (N+). SNAP is found in 20-26% of cognitively normal (CN)
      individuals aged 65 years or older and 17-35% of individuals with mild cognitive
      impairment (MCI). Similarly, 7-39% of patients with clinically probable
      Alzheimer's disease (AD) dementia are negative for Abeta. The epsilon4 allele of
      the apolipoprotein E gene is underrepresented in individuals with SNAP compared
      with amyloid-positive (A+) groups. The progression of the cognitive impairments
      of individuals with SNAP was slower than that of A+N+ subjects who had a high
      likelihood of AD pathophysiology and faster than that of A-N- subjects. The
      pathological backgrounds of the individuals with SNAP were heterogeneous and
      included cerebrovascular disorders, mixed pathologies, and non-AD
      neurodegeneration, such as primary age-related tauopathy [PART, also known as
      senile dementia of the neurofibrillary tangle type (SD-NFT) (tangle-only
      dementia) at the dementia stage] and argyrophilic grain disease. Further
      clarification of SNAP is needed to better define the mechanisms underlying the
      progression of AD pathologies in older individuals.

PMID- 29348376
TI  - [Benign Outcome of Cochlear Implantation in a Patient with Superficial
      Siderosis].
AB  - We report the case of a 38-year-old man with gait disorder and hearing loss. The
      patient had developed gait disorder due to a cervical meningioma since 4 year-old
      disappeared for 15 years after the surgical removal of the meningioma. However,
      at the age of 21 year-old, the gait disorder reappeared and worsened
      progressively. Sensorineural hearing loss (SNHL) and epileptic seizures developed
      during the disease course, and he was diagnosed with superficial siderosis (SS).
      When he was 37 years old, he experienced sudden-onset of right-side hearing
      impairment and was considered a candidate for cochlear implantation (CI) at the
      otorhinolaryngology clinic of the nearby University Hospital. He underwent CI in
      November 2014. Eight months after the operation, his right side hearing improved
      although ataxia, hearing loss, and pyramidal sign persisted. At the long term
      follow-up of 29 months after CI, his hearing remained at the improved level.
      Thus, CI may be an effective long-term treatment for SNHL in patients with SS and
      could prevent the progression of his hearing loss. (Received February 1, 2017;
      Accepted August 23, 2017; Published January 1, 2018).

PMID- 29348377
TI  - Are We Ready for National Diabetes Prevention Program?

PMID- 29348378
TI  - Analysis of Diabetes Mellitus Determinants in Indonesia: A Study from the
      Indonesian Basic Health Research 2013.
AB  - BACKGROUND: diabetes mellitus is a silent-killer. Its prevalence and impact on
      health expenses increase from year to year. This study aims to investigate the
      characteristics and the risk factors that affect  diabetes mellitus in Indonesia.
      METHODS: this is a cross sectional study. Data were obtained from the Basic
      Health Research (RISKESDAS) in 2013. The samples were individuals aged >=15
      years, whose fasting blood glucose and 2 hours blood glucose after the imposition
      have been measured. 38.052 individuals were selected for this study. The
      variables of age, sex, marital status, level of education, employment status,
      living area, regional status, hypertension, obesity, smoking habit, and
      dyslipidemia are analyzed as risk factors for diabetes mellitus. Bivariate
      analysis was using chi-square test with significance level of p<0.05 and
      confidence interval (CI) of 95%, and multivariate analysis using multiple
      logistic regression test. RESULTS: our study showed that 13% have diabetes
      mellitus in 2013. Factors affecting diabetes mellitus were age>55 years (OR=5.10;
      95%CI 4.42 to 5.89; p<0.001), female (OR=1.37; 95%CI 1.26 to 1.49; p<0.001),
      rural (OR=1.16; 95%CI 1.08 to 1.26; p<0.001), married (OR=1.31; 95%CI 1.07 to
      1.58; p<0.05), unemployed (OR=1.14; 96%CI 1.05 to 1.23; p<0.05), obesity
      (OR=1.46; 95%CI 1.35 to 1.58; p<0.001), hypertension (OR=1.68; 95%CI 1.55 to
      1.81; p<0.001) and dyslipidemia (OR=1.53; 95%CI 1.39- 1.68; P<0.001). CONCLUSION:
      as many as 13% of individuals have diabetes mellitus in 2013. Age, gender, living
      area, employment status, obesity, hypertension, and dyslipidemia are the
      contributing factors to diabetes mellitus.

PMID- 29348379
TI  - The Differences in Serum Quantitative Specific IgE Levels Induced by
      Dermatophagoides pteronyssinus, Dermatophagoides farinae and Blomia tropicalis
      Sensitization in Intermittent and Persistent Allergic Asthma.
AB  - BACKGROUND: house dust mites (HDM) are an important inhalant allergen in allergic
      asthma. However, molecular diagnostic study of specific IgE to HDM allergens has
      not been done in Indonesia. In addition, the association of quantitative specific
      IgE measurement with asthma severity has not been investigatedd. This study aimed
      to investigate the difference of serum quantitative specific IgE levels induced
      by Dermatophagoides (D.) pteronyssinus, D. farinae and Blomia tropicalis
      sensitization in intermittent and persistent allergic asthma. METHODS: this was a
      cross-sectional study on adult allergic asthma patients who were invited for
      serum specific IgE testing. This study was a part of a larger study within the
      Division of Allergy and Immunology, Cipto Mangunkusumo Hospital. Asthma severity
      was defined based on Global Initiative on Asthma (GINA) 2015 criteria and were
      grouped as intermittent or persistent. Quantitative specific IgE testing was done
      on blood serum using a multiple allergosorbent test (Polycheck Allergy, Biocheck
      GmbH, Munster, Germany). The HDM allergens tested were D. pteronyssinus, D.
      farinae, and Blomia tropicalis. Difference between two groups were analyze using
      Mann-Whitney test. RESULTS: a total of 87 subjects were enrolled in this study;
      69 (79.3%) were women. Mean patients' age was 40, 2 years. Sixty-three (72.4%)
      subjects had asthma and allergic rhinitis. Fifty-eight (66.7%) subjects were
      classified as persistent asthma. The prevalence of sensitization was 62.1% for D.
      farinae, 51.7% for D. pteronyssinus, and 48.3% for Blomia tropicalis. The median
      of specific IgE levels were significantly higher in persistent asthma compares to
      intermittent asthma induced by D. farinae (median 1.30 vs. 0.0 kU/L; p=0.024) and
      B. tropicalis (median 0.57 vs. 0.0 kU/L; p=0.015) sensitization. Level of
      Specific IgE  D. pteronyssinus was also to be higher in persistent asthma than
      the level measured in intermittent asthma (0.67 vs. 0.00 kU/L; p=0.066).
      CONCLUSION: Sensitization of HDM allergens was shown to be highest for D. farinae
      62.1%, followed by D. pteronyssinus 51.7% and Blomia tropicalis 48.3%. Specific
      IgE level induced by D. farinae and Blomia tropicalis sensitization were
      significantly higher in patients with persistent asthma compared to intermittent
      asthma, whereas specific IgE level induced by D. pteronyssinus sensitization was
      higher in persistent asthma although not statistically significant.

PMID- 29348380
TI  - Effect of Nigella sativa Seed Extract for Hypertension in Elderly: a Double
      blind, Randomized Controlled Trial.
AB  - BACKGROUND: Nigella sativa (NS) seed extract shows diuretic activity, inhibits
      sympathetic nervous system overactivity and increases the production of Nitric
      Oxide in in vivo studies, thus it has a potential use as an adjuvant
      antihypertensive for elderly population. This study aimed to determine the effect
      of Nigella sativa seed extract to systolic blood pressure (SBP) and diastolic
      blood pressure (DBP) of elderly patients with hypertension. METHODS: a double
      blind, randomized controlled trial was conducted on elderly subjects with
      hypertension in three outpatient clinics in Cipto Mangunkusumo National Hospital
      Jakarta Indonesia from June to September 2011. Subjects were divided into
      intervention group given 300 mg Nigella sativa seed extract twice daily for 28
      days and into another group which was given placebo. Blood pressure were measured
      on day 1 and 28. Intention to treat analysis using unpaired t-test to compare
      blood pressure after intervention between the two groups was performed. RESULTS:
      of a total of 85 patients, 76 subjects fulfilled the study criteria and were
      randomized into 2 groups, with 38 subjects in each group. Both groups were
      comparable in all important prognostic factors. The mean systolic blood pressure
      of the NS group was decreased from 160.4 (SD 15.7) mmHg to 145.8 (SD 19.8) mmHg,
      and from 160.9 (16.3) mmHg to 147.53 (SD 22.0) mmHg in the placebo group
      (p=0.36). The mean diastolic blood pressure in the NS group was decreased from
      78.3 (SD 11.9) to 74.4 (SD 8.2) mmHg, and from 79.0 (SD 12.4) to 78.2 (SD 8.9) in
      the placebo group (p=0.35). Reported adverse events include dyspepsia in 6
      subjects (15.7%), nausea in 3 subjects (7.8%), and constipation in 2 subjects
      (5.2%). No electrolyte abnormalities, liver and renal toxicities, or orthostatic
      hypotension were observed. CONCLUSION: although a trend towards a slight decrease
      in blood pressure was observed, Nigella sativa has not been proven to be
      effective in reducing blood pressure in elderly patients with hypertension.

PMID- 29348381
TI  - Thyroid Dysfunction in Type 2 Diabetes Mellitus Patients.
AB  - BACKGROUND: thyroid dysfunction is more likely to occur in diabetes mellitus
      patients than general population. Until now, no study has been done to find
      prevalence of hypothyroidism and hyperthyroidism in Indonesian diabetics. This
      study aimed to find the proportion and characteristics of thyroid dysfunction in
      Indonesian type 2 diabetes mellitus patients. METHODS: a cross-sectional study
      was conducted in Endocrine and Diabetes Polyclinic, Department of Internal
      Medicine, Cipto Mangunkusumo Hospital from July to September 2015. This study
      include type 2 diabetes mellitus patients, age >= 18 year-old, willing to undergo
      thyroid laboratory testing. In this study, hypothyroidism defined as TSH more
      than 4.0 mIU/L, while hyperthyroidism is defined as TSH less than 0.4 mIU/L with
      eCLIA. RESULTS: from 364 subjects who were recruited from Endocrine and Diabetes
      Polyclinic, Cipto Mangunkusumo Hospital, 303 subjects underwent this study until
      analysis. Two hundred and three (273) subjects (90.1%) were euthyroid, 7 subjects
      (2.31%) were hyperthyroid, and 23 subjects (7.59%) were hypothyroid. Majority of
      the patients had subclinical hypothyroidism (56.5% based on Zulewski and
      Billewicz Score and 65.2% based on fT4 laboratory result), while 42.9% and 71.4%
      subjects had clinical hyperthyroidism based on clinical appearance and fT4
      laboratory result respectively. CONCLUSION: proportion of hypothyroidism was
      7.59% and hyperthyroidism was 2.31%, while the proportion of total thyroid
      dysfunction was 9.9% among diabetics. It is suggested that screening for thyroid
      dyscfunction can be done in high risk condition as a part of comprehensive
      management in type 2 diabetes mellitus patients.

PMID- 29348382
TI  - The Effect of Ophiocephalus striatus Extract on the Levels of IGF-1 and Albumin
      in Elderly Patients with Hypoalbuminemia.
AB  - BACKGROUND: a freshwater fish Ophiocephalus striatus or known locally to
      Indonesian as haruan,can potentially increases IGF-1 and albumin levels in
      elderly patients with hypoalbuminemia due to the contents of amino acids, fatty
      acids, vitamins, and minerals. This study was conducted to investigate the effect
      of Ophiocephalus striatus extract on the level of IGF-1 and albumin in elderly
      patients with hypoalbuminemia. METHODS: the study is a double-blind randomized
      controlled trial involving malnourished elderly inpatients (>=60 years old)
      recovering from acute condition before hospital discharge, with Mini Nutritional
      Assessment score <=23.5 and albumin level <3.5 g/dL. A total of 109 subjects were
      randomly divided into two groups: one group received 10 g Ophiocephalus striatus
      extract per day for 14 days and another group received placebo. Albumin and IGF-1
      levels were obtained before and after intervention. RESULTS: ninety subjects
      completed the study (extract group=45 subjects; placebo group =45 subjects) for
      14 days. The median of age were 69 (64;75) years and the male to female ratio
      were 2 : 3. The changes of IGF-1 and albumin levels from before to after
      intervention between extract group compared to placebo group were 14.7
      (0.30;31.5) ng/mL vs 1.0 (-6;13.15) ng/mL (p=0.002) and 0.5 (0.15;0.70) g/dL vs
      0.10 (0.0;0.50) g/dL (p=0.003), respectively. There were significant differences
      in the improvement of IGF-1 and albumin levels between extract and placebo group.
      CONCLUSION: supplementation of Ophiocephalus striatus extract was associated with
      a significant increase in IGF-1 and albumin levels in elderly patients with
      hypoalbuminemia.

PMID- 29348383
TI  - Improving Diagnostic of Pulmonary Tuberculosis in HIV Patients by Bronchoscopy: A
      Cross Sectional Study.
AB  - BACKGROUND: diagnostic of pulmonary TB in HIV patients is a problem due to non
      specific clinical features, or radiological appearance. HIV patients with
      CD4<=200 cells/mL infected with M. tuberculosis have less capacity in containing
      M. tuberculosis, developing granulomas, casseous necrosis, or cavities. This
      condition is caused by weakend inflammatory which later reduced sputum production
      and may cause false negative result. This study aimed to assess differences in
      the positivity level of acid fast bacilli (AFB) and cultures of M. tuberculosis
      from non-bronchoscopic sputum (spontaneous and induced sputum) compared to
      bronchoscopic sputum (bronchoalveolar lavage) in HIV positive patients suspected
      pulmonary tuberculosis with CD4<200 cells/MUL. METHODS: this cross sectional
      study was conducted in adult HIV patients treated in Hasan Sadikin Hospital with
      CD4<=200 cells/MUL suspected with pulmonary tuberculosis by using paired
      comparative analytic test. All patients expelled sputum spontaneously or with
      sputum induction on the first day. On the next day, bronchoalveolar lavage (BAL)
      was performed. The two samples obtained from two methods were examined by AFB
      examination with staining Ziehl Neelsen (ZN) and cultured of M. tuberculosis on
      solid media Ogawa on all patients. Positivity, sensitivity and increased
      sensitivity of AFB and culture of M. tuberculosis in the non bronchoscopic and
      bronchoscopic groups were compared. RESULTS: there were differences in the
      positivity level of AFB with ZN staining between non-bronchoscopic and
      bronchoscopic groups which were 7/40 (17.5%) vs 20/40 (50.0%) (p<0.001). The
      differences between the cultures of non-bronchoscopic and bronchoscopic groups
      were 16/40 (40.0%) vs 23/40 (57.5%) (p=0.039). Bronchoscopic sputum increased the
      positivity level of the ZN AFB examination by 32.5% (from 17.5% to 50.0%) as well
      as on culture examination by 17.5% (from 40.0% to 57.5%). CONCLUSION:
      Bronchoalveolar lavage can improve the positivity level of smears and cultures in
      patients suspected of pulmonary TB in HIV patients with CD4<200 cells/MUL.

PMID- 29348384
TI  - Clinical Outcomes of Geriatric Care in Cipto Mangunkusumo Hospital, Before and
      After the Implementation of National Health Insurance Program.
AB  - BACKGROUND: the National Health Insurance (NIH/JKN) has been enacted since
      January 2014. Various outcomes of geriatric patient care, such as improved
      functional status and quality of life have not been evaluated. Prolonged
      hospitalization and re-hospitalization are potentially affecting the efficiency
      care of this vulnarable group. This study aimed to identify the differences of
      functional status improvement, quality of life improvement, length of stay, and
      hospitalization of geriatric patients admitted to CMH between prior to and after
      NHI implementation. METHODS: a cohort study with historical control was conducted
      among geriatric patients admitted to Acute Geriatric Ward CMH Hospital on two
      periods of time: January-December 2013 (pre-NHI implementation) and June 2014-May
      2015 (after NHI implementation). Patients who died within 24 hours of hospital
      admission, those with APPACHE II score >24, advance stage cancer, transfer to
      other wards before they were discharged or have incomplete record were excluded
      from the study. Data on demographical and clinical characteristics, functional
      status, quality of life, length of stay, and re-hospitalization were taken from
      patient's medical record. The differences of studied outcomes were analyzed using
      t-test or Mann-Whitney test. RESULTS: there were 102 subjects in pre-NHI and 135
      subjects in NHI groups included in the study. Median lengths of stay were not
      different between two groups (12.5 days in pre-NHI and 10 days in NHI groups,
      p=0.087), although the proportion of patients with in-hospital stay less than 14
      days was higher in NHI group. The difference of functional status of discharged
      patients in pre-NHI and NHI groups were 3 and 3 (p=0.149) respectively, whereas
      for health-related quality of life, although NHI group in the beginning showed a
      lower quality of life compared to the pre-NHI (0.163 [0.480] vs. 0.243 [0.550];
      p=0.012). However, after incorporating comprehensive geriatric assessment (CGA)
      the quality of life improved significantly by the end of in-hospital care in both
      groups. Re-hospitalization incidence in NHI group was lower compared to pre-NHI
      (7 [5.2%] vs. 13 [12.7%]; p=0.038). CONCLUSION: our study shows that there was 
      no  significant difference regarding length of stay, functional status, and
      health-related quality of life between prior to and after national health
      insurance implementation on admitted geriatric patients. Rehospitalization
      incidence showed better results in NHI group and hence NHI implementation is
      favored.

PMID- 29348385
TI  - A Rare Case Series of Ischemic Stroke Following Russell's Viper Snake Bite in
      India.
AB  - Snakebite is an important medical problem in India. Among their various
      manifestations, cerebral complications are uncommonly found in literature.
      Moreover, Ischemic stroke following snake bite is quite rare. Here we report a
      case series of two such cases that developed neurological manifestations
      following Russell's viper bite. On computerized tomography (CT) scan of brain;
      cerebral infarcts were revealed. Their likely mechanisms are discussed in present
      study which include disseminated intravascular coagulation, toxin induced
      vasculitis and endothelial damage.

PMID- 29348386
TI  - ST Elevation in Lead aVR and Its Association with Clinical Outcomes.
AB  - The purpose of this case repots are to evaluate the role of ST elevation in aVR
      lead and to make analysis between both cases. There are some atypical
      electrocardiogram (ECG) presentations which need prompt management in patient
      with ischemic clinical manifestation such as ST elevation in aVR lead. In this
      case study, we report a 68-year old woman with chief symptoms of shortness of
      breath and chest discomfort. She was diagnosed with cardiogenic shock, with
      Killip class IV, and TIMI score of 8. The second case is a 57-year-old man with
      typical chest pain at rest which could not be relieved with nitrate treatment. He
      was diagnosed with ST elevation in inferior and aVR lead, and occlusion in left
      circumflex artery (LCX). Both patients underwent primary percutaneous coronary
      intervention (PPCI). Subsequently, both cases presented remarkable clinical
      improvements and improved ST elevation myocardial infarction (STEMI) in aVR lead.

PMID- 29348387
TI  - Cancer Stem Cells and Molecular Biology Test in Colorectal Cancer: Therapeutic
      Implications.
AB  - Colorectal cancer (CRC) is the third most frequent cancer in males, the second in
      females, and is the second leading cause of cancer related death worldwide.
      Within Indonesia's 250 million population, the incidence rates for CRC per
      100,000 population were 15.2 for males and 10.2 for females, and estimated 63,500
      cases per year.  More than 50% of colorectal cancer patients will develop
      metastasis. CRC is still the main cause of tumor-related death, and although most
      CRC patients are treated with surgery to remove the tumor tissue, some of the CRC
      patients recurred. Chemotherapy used as adjuvant or neoadjuvant therapy also has
      several problems, in which these treatments are useless in tumor cells with chemo
      resistance. Molecular testing of CRC from tumor tissues has important
      implications for the selection of treatment. Biomarkers can be used as prognostic
      value, molecular predictive factors, and targeted therapy. Recent research
      reported that, cancer stem cells (CSCs) are considered as the origin of
      tumorigenesis, development, metastasis and recurrence. At present, it has been
      shown that CSCs existed in many tumors including CRC. This review aims to
      summarize the issue on CSCs, and the future development of drugs that target
      colorectal cancer stem cells.

PMID- 29348388
TI  - Disseminated Histoplasmosis in an Indonesian HIV-Positive Patient: A Case
      Diagnosed by Fine Needle Aspiration Cytology.
AB  - A 30-year-old Javanese-Indonesian man was admitted with complaints of 3 months
      persistent fever, weight loss, and fatigue. He had never known his past history
      of unprotected HIV until the admission. His only risk factor is unsafe sex. The
      patient seemed well nourished. Physical examination revealed blood pressure
      100/60 mmHg, pulse 100 beats per minute, respiratory rate 20 times per minute,
      and temperature 38.8 degrees C. Multiple cervical and inguinal lymphadenopathies
      were also found. Electrocardiogram showed anterolateral ischemic finding, whereas
      chest X-ray were normal. Laboratory test results revealed pancytopenia with
      hemoglobin of 8.2 g/dL, leucocyte count 2000 cells/mm3, platelet 78000 cells/mm3,
      hematocrit 25.8%, AST 162 IU/L, ALT 81 IU/L, decreased albumin of 2.72 g/dL. The
      clinical differential diagnosis were lymphoma or tuberculosis lymphadenopathy.

PMID- 29348389
TI  - Efficacy of Curcumin as Adjuvant Therapy to Induce or Maintain Remission in
      Ulcerative Colitis Patients: an Evidence-based Clinical Review.
AB  - BACKGROUND: treatment guidelines for ulcerative colitis (UC) not yet established.
      Currently, mesalazine, corticosteroids, and immunomodulators are treatment
      options for UC. However, they are known to have unpleaseant side effects such as
      nausea, vomiting, headaches, hepatitis, and male infertility. Curcumin is found
      in Turmeric plants (Curcuma longa L.), which possesses both anti-inflammatory and
      antioxidant properties. This study aimed to determine whether curcumin as
      adjuvant therapy can induce or maintain remission in UC patients. METHODS:
      structured search in three database (Cochrane, PubMed, Proquest) using
      "Curcumin", "remission" and "Ulcerative Colitis" as keywords. Inclusion criteria
      is randomized controlled trials (RCTs), meta-analysis, or systematic review using
      curcumin as adjuvant therapy in adult UC patients. RESULTS: we found 49 articles.
      After exclusion, three RCTs were reviewed; two examined curcumin efficacy to
      induce remission and one for remision maintenance in UC. Curcumin was
      significantly more effective than placebo in all RCTs. The efficacy of curcumin
      could be explained by its anti-inflammatory properties, which inhibit NF-kB
      pathway. Regulation of oxidant/anti-oxidant balance can modify the release of
      cytokines. However, methods varied between RCTs. Therefore, they cannot be
      compared objectively. Futhermore, the sample size were small (n= 50, 45, 89)
      therefore the statistical power was not enough to generate representative results
      in all UC patients. CONCLUSION: Available evidence showed that curcumin has the
      potential to induce and maintain remission in UC patients with no serious side
      effects. However, further studies with larger sample size are needed to recommend
      it as adjuvant therapy of ulcerative colitis.

PMID- 29348390
TI  - Current and Emerging Therapy on Lupus Nephritis.
AB  - Lupus nephritis (LN) is involvement of the kidney in patient with systemic lupus
      erythematosus (SLE) and one of the most common target organ in SLE. The diagnosis
      of LN will significantly impact the clinical outcome and therapy of the patient.
      Therapy regiment of LN is divided into two stages, induction and maintenance
      treatment. The main objective of the induction therapy is to achieve complete or
      partial remission as soon as possible since it is correlated with better
      prognosis and fewer relapse incidence. In the maintenance stage, the main aim of
      the therapy is to maintain the remission status and avoid future relapse. It is
      also important to evaluate the effectiveness of the therapy as it will affect the
      duration and the regiment therapy being used. Corticosteroid, cyclophosphamide,
      mycophenolate mofetil, azathrioprine, cyclosporine and tacrolimus are example of
      drugs used in LN therapy. Currently, studies are being conducted to evaluate and
      develop targeted drug therapy to further add treatment options for LN.

PMID- 29348391
TI  - Effects of senescence and angiotensin II on expression and processing of amyloid
      precursor protein in human cerebral microvascular endothelial cells.
AB  - The present study was designed to determine the effects of senescence and
      angiotensin II (Ang II) on expression and processing of amyloid precursor protein
      (APP) in human brain microvascular endothelial cells (BMECs). Senescence caused a
      decrease in APP expression thereby resulting in reduced secretion of soluble
      APPalpha (sAPPalpha). In contrast, beta-site APP cleaving enzyme (BACE1)
      expression and production of amyloid beta (Abeta)40 were increased in senescent
      endothelium. Importantly, in senescent human BMECs, treatment with BACE1
      inhibitor IV inhibited Abeta generation and increased sAPPalpha production by
      enhancing a disintegrin and metalloprotease (ADAM)10 expression. Furthermore, Ang
      II impaired expression of ADAM10 and significantly reduced generation of
      sAPPalpha in senescent human BMECs. This inhibitory effect of Ang II was
      prevented by treatment with BACE1 inhibitor IV. Our results suggest that
      impairment of alpha-processing and shift to amyloidogenic pathway of APP
      contribute to endothelial dysfunction induced by senescence. Loss of sAPPalpha in
      senescent cells treated with Ang II exacerbates detrimental effects of senescence
      on APP processing. Notably, inhibition of BACE1 has beneficial effects on
      senescence induced endothelial dysfunction. Reported findings may help to explain
      contributions of senescent cerebral microvascular endothelium to development of
      cerebral amyloid angiopathy and Alzheimer's disease (AD) pathology.

PMID- 29348392
TI  - Rapamycin prevents the intervertebral disc degeneration via inhibiting
      differentiation and senescence of annulus fibrosus cells.
AB  - The effects of bleomycin and rapamycin on cellular senescence and differentiation
      of rabbit annulus fibrosus stem cells (AFSCs) were investigated using a cell
      culture model. The results showed that bleomycin induced cellular senescence in
      AFSCs as evidenced by senescence-associated secretory phenotype. The morphology
      of AFSCs was changed from cobblestone-like cells to pancake-like cells. The
      senescence-associated beta-galactosidase activity, the protein expression of P16
      and P21, and inflammatory-related marker gene levels IL-1beta, IL-6, and TNF
      alpha were increased in bleomycin-treated AFSCs in a dose-dependent manner.
      Rapamycin treatment decreased the gene expression of MMP-3, MMP-13, IL-1beta, IL
      6, TNF-alpha, and protein levels of P16 and P21 in bleomycin-treated AFSCs.
      Furthermore, neither bleomycin nor rapamycin changed the ribosomal S6 protein
      level in AFSCs. However, the phosphorylation of the ribosomal S6 protein was
      increased in bleomycin-treated AFSCs and decreased in rapamycin-treated AFSCs.
      AFSCs differentiated into adipocytes, osteocytes, and chondrocytes when they were
      cultured with respective differentiation media. Rapamycin inhibited multi
      differentiation potential of AFSCs in a concentration-dependent manner. Our
      findings demonstrated that mammalian target of rapamycin (mTOR) signaling affects
      cellular senescence, catabolic and inflammatory responses, and multi
      differentiation potential, suggesting that potential treatment value of rapamycin
      for disc degenerative diseases, especially lower back pain.

PMID- 29348393
TI  - Epigenetics: the panacea for cognitive decline?

PMID- 29348394
TI  - HOXC6 predicts invasion and poor survival in hepatocellular carcinoma by driving
      epithelial-mesenchymal transition.
AB  - Aberrant expression of HOXC6 has been reported in several malignant tumors, yet
      little is known about the value of HOXC6 in invasion and prognosis of
      hepatocellular carcinoma (HCC). HOXC6 expression was positively correlated with
      high AFP level, liver cirrhosis, larger tumor, vascular invasion and BCLC stage.
      Kaplan-Meier analysis revealed that HOXC6 was an independent predictor for
      overall survival (OS) and time to recurrence (TTR). In addition, HOXC6 status
      could act as prognostic predictor in different risk subgroups. Moreover, HOXC6
      maintained its prognostic value in different ability of invasiveness.
      Furthermore, combination of HOXC6 and serum AFP could be a potential predictor
      for survival in HCC patients. Additionally, further study showed that HOXC6 may
      promote invasion of HCC by driving epithelial-mesenchymal transition (EMT).
      Knockdown of HOXC6 significantly decreased the migration and invasion of HCC
      cells and changed the expression pattern of EMT markers. An opposite expression
      pattern of EMT markers was observed in HOXC6-transfected cells. In addition,
      immunohistochemistry and RT-PCR results further confirmed this correlation. In
      conclusion, HOXC6 contributes to invasion by inducing EMT pathway and predicts
      poor prognosis of HCC. HOXC6/AFP expression may help to distinguish the different
      risks of HCC patients after hepatectomy.

PMID- 29348395
TI  - NKILA inhibits NF-kappaB signaling and suppresses tumor metastasis.
AB  - The long non-coding RNA (lncRNA) NKILA (nuclear transcription factor NF-kappaB
      interacting lncRNA) functions as a suppressor in human breast cancer and tongue
      cancer. However, the clinical significance and biological roles of NKILA in
      esophageal squamous cell carcinoma (ESCC) remain unknown. In this study, we
      showed that NKILA was downregulated in ESCC tissues and cancer cells compared
      with their normal counterparts. Low NKILA expression correlated with large tumor
      size and advanced TNM stage, and predicted poor overall and disease-free survival
      of ESCC patients. Further loss- and gain-of-function assays indicated that NKILA
      inhibited proliferation and migration of ESCC cells in vitro, suppressed tumor
      growth and lung metastasis in vivo. Mechanistically, NKILA could inhibit
      phosphorylation of IkappaBalpha, suppress p65 nuclear translocation and
      downregulate the expression of NF-kappaB target genes in ESCC cells. These
      results suggest NKILA could suppress malignant development of ESCC via abrogation
      of the NF-kappaB signaling and may potentially serve as a prognostic marker for
      ESCC.

PMID- 29348396
TI  - A Case of Umbilical Artery Thrombosis in the Third Trimester of Pregnancy.
AB  - BACKGROUND Umbilical artery thrombosis is an extremely rare complication during
      pregnancy. Umbilical artery thrombosis has a poor prognosis and is associated
      with increased rates of perinatal morbidity, including intrauterine growth
      restriction (IUGR), and fetal mortality. CASE REPORT We report a rare case of
      umbilical artery thrombosis, diagnosed by ultrasound, at 33 weeks gestation in a
      30-year-old woman who had previously had an uneventful pregnancy. CONCLUSIONS
      Umbilical artery thrombosis is a rare complication of pregnancy that is
      associated with high fetal mortality. Management may include planned elective
      delivery by cesarean section, following antenatal corticosteroid therapy for
      fetal lung maturation.

PMID- 29348397
TI  - Placement of an Aortohepatic Conduit as an Alternative to Standard Arterial
      Anastomosis in Liver Transplantation.
AB  - BACKGROUND The aim of this study was to assess the impact of placement of an
      aortohepatic conduit on graft and patient survival after liver transplantation
      (LT) in selected patients with an inadequate recipient hepatic artery (HA) for a
      standard arterial anastomosis. MATERIAL AND METHODS Of 331 patients who underwent
      deceased donor LT, 25 (7.6%) who received placement of an aortohepatic conduit at
      the time of transplantation were included. Clinical characteristics and outcomes,
      including postoperative complications, conduit patency, and graft and patient
      survival rates, were analyzed. RESULTS All 25 patients included in this study
      presented a high preoperative Model for End-stage Liver Disease score (25.4+/
      8.6; range, 6-42) and high rates of retransplantation (n=11, 44%) or previous
      abdominal - pelvic surgery (n=5, 20%). The observed postoperative vascular
      complications were portal vein thrombosis in 3 cases (12%) and anastomosis-site
      bleeding of the aortohepatic conduit in 1 case (4%); there was no HA thrombosis
      or stenosis in our analysis. With a median follow-up of 37 months (range, 0-69
      months), all aortohepatic conduits were patent, and the graft and patient
      survival rates were 84% and 68%, respectively. The causes of death were graft
      failure (n=4), pneumonia (n=3), and cerebrovascular accidents (n=1). CONCLUSIONS
      Our results indicate that placement of an aortohepatic conduit is a feasible
      alternative to a standard arterial anastomosis in selected patients whose HA and
      surrounding potential inflow arteries are not suitable for standard arterial
      anastomosis.

PMID- 29348398
TI  - Association Study of Polymorphisms in Genes Relevant to Vitamin B12 and Folate
      Metabolism with Childhood Autism Spectrum Disorder in a Han Chinese Population.
AB  - BACKGROUND Both genetic and environmental factors play a role in the development
      of autism spectrum disorder (ASD). This case-control study examined the
      association between childhood ASD and single-nucleotide polymorphisms (SNPs) in
      genes involved with vitamin B12 and folate metabolism. MATERIAL AND METHODS
      Genotypes of transcobalamin 2 (TCN2) rs1801198, methionine synthase (MTR)
      rs1805087, methionine synthase reductase (MTRR) rs1801394, and methylene
      tetrahydrofolate reductase (MTHFR) rs1801133 were examined in 201 children with
      ASD and 200 healthy controls from the Han Chinese population. RESULTS Our results
      showed no association of all examined SNPs with childhood ASD and its severity.
      CONCLUSIONS None of the examined SNPs were a risk factor for the susceptibility
      to childhood ASD and severity of the disease in a Han Chinese population.

PMID- 29348399
TI  - Insulin-like growth factor 2 is a key mitogen driving liver repopulation in mice.
AB  - Hepatocyte transplantation holds great promise as an alternative to orthotopic
      organ transplantation in the treatment of liver diseases. However, obtaining
      clinically meaningful levels of liver repopulation has not been achieved because
      the mechanisms regulating hepatocyte proliferation in recipient livers have not
      yet been well characterized. In the mouse model of Hereditary Tyrosinemia Type I,
      the fumarylacetoacetate hydrolase-deficient (Fah-/-) mouse, we found gradually
      increasing expression level of insulin-like growth factor 2 (IGF2) in the
      hepatocytes of host livers. Similarly, high levels of IGF2 were found in the
      livers of patients with deficient FAH activity. Recombinant IGF2 directly
      promotes proliferation of primary hepatocytes in vitro. Inhibition on IGF2
      expression through the interruption of PI3K/Akt and MAPK pathways significantly
      reduced the level of liver repopulation in Fah-/- mice. Interestingly, treatment
      with IGF2 before hepatocyte transplantation generally improved the amount of
      liver repopulation seen in various mice models of liver injury. Altogether, these
      findings underscore the underlying mechanisms of therapeutic liver repopulation
      in Fah-/- mice, and indicate that IGF2 is a potential hepatocyte mitogen for
      liver cell transplantation therapies.

PMID- 29348400
TI  - Monoglyceride lipase gene knockout in mice leads to increased incidence of lung
      adenocarcinoma.
AB  - Monoglyceride lipase (MGL) is a recently discovered cancer-related protein. The
      role of MGL in tumorigenesis remains to be fully elucidated. We have previously
      shown that MGL expression was reduced or absent in multiple human malignancies,
      and overexpression of MGL inhibited cancer cell growth. Here, we have generated
      the MGL knockout mice to further investigate the role of MGL in tumorigenesis in
      vivo. Our results indicate that MGL-deficient (MGL+/-, MGL-/-) mice exhibited a
      higher incidence of neoplasia in multiple organs, including the lung, spleen,
      liver and lymphoid tissues. Interestingly, lung neoplasms were the most common
      neoplastic changes in the MGL-deficient mice. Importantly, MGL-deficient animals
      developed premalignant high-grade dysplasia and adenocarcinomas in their lungs.
      Investigation of the MGL expression status in lung cancer specimens from patients
      also revealed that MGL expression was significantly reduced in the majority of
      primary human lung cancers when compared to corresponding matched normal tissues.
      Furthermore, mouse embryonic fibroblasts (MEFs) from MGL-deficient animals showed
      characteristics of cellular transformation including increased cell
      proliferation, foci formation and anchorage-independent growth. Our results also
      indicate that MGL deficiency was associated with activation of EGFR and ERK. In
      addition, pro-inflammatory molecules COX-2 and TNF-alpha were also activated in
      the MGL-deficient lung tissues. Thus, our results provide new insights into the
      novel role of MGL as an important negative regulator of EGFR, COX-2 and TNF
      alpha. Accordingly, EGFR and COX-2/TNF-alpha activation/induction is expected to
      play important roles in MGL deficiency-driven lung tumors. Collectively, our
      results implicate the tumor suppressive role of MGL in preventing tumor
      development in vivo, particularly in context to the lung cancer, and highlight
      its role as a potential tumor suppressor.

PMID- 29348401
TI  - Three-dimensional bicontinuous nanoporous materials by vapor phase dealloying.
AB  - Three-dimensional bicontinuous open (3DBO) nanoporosity has been recognized as an
      important nanoarchitecture for catalysis, sensing, and energy storage.
      Dealloying, i.e., selectively removing a component from an alloy, is an efficient
      way to fabricate nanoporous materials. However, current electrochemical and
      liquid-metal dealloying methods can only be applied to a limited number of alloys
      and usually require an etching process with chemical waste. Here, we report a
      green and universal approach, vapor-phase dealloying, to fabricate nanoporous
      materials by utilizing the vapor pressure difference between constituent elements
      in an alloy to selectively remove a component with a high partial vapor pressure
      for 3DBO nanoporosity. We demonstrate that extensive elements, regardless of
      chemical activity, can be fabricated as nanoporous materials with tunable pore
      sizes. Importantly, the evaporated components can be fully recovered. This
      environmentally friendly dealloying method paves a way to fabricate 3DBO
      nanoporous materials for a wide range of structural and functional applications.

PMID- 29348402
TI  - Self-generated surface magnetic fields inhibit laser-driven sheath acceleration
      of high-energy protons.
AB  - High-intensity lasers interacting with solid foils produce copious numbers of
      relativistic electrons, which in turn create strong sheath electric fields around
      the target. The proton beams accelerated in such fields have remarkable
      properties, enabling ultrafast radiography of plasma phenomena or isochoric
      heating of dense materials. In view of longer-term multidisciplinary purposes
      (e.g., spallation neutron sources or cancer therapy), the current challenge is to
      achieve proton energies well in excess of 100 MeV, which is commonly thought to
      be possible by raising the on-target laser intensity. Here we present
      experimental and numerical results demonstrating that magnetostatic fields self
      generated on the target surface may pose a fundamental limit to sheath-driven ion
      acceleration for high enough laser intensities. Those fields can be strong enough
      (~105 T at laser intensities ~1021 W cm-2) to magnetize the sheath electrons and
      deflect protons off the accelerating region, hence degrading the maximum energy
      the latter can acquire.

PMID- 29348403
TI  - Ice volume and climate changes from a 6000 year sea-level record in French
      Polynesia.
AB  - Mid- to late-Holocene sea-level records from low-latitude regions serve as an
      important baseline of natural variability in sea level and global ice volume
      prior to the Anthropocene. Here, we reconstruct a high-resolution sea-level curve
      encompassing the last 6000 years based on a comprehensive study of coral
      microatolls, which are sensitive low-tide recorders. Our curve is based on
      microatolls from several islands in a single region and comprises a total of 82
      sea-level index points. Assuming thermosteric contributions are negligible on
      millennial time scales, our results constrain global ice melting to be 1.5-2.5 m
      (sea-level equivalent) since ~5500 years before present. The reconstructed curve
      includes isolated rapid events of several decimetres within a few centuries, one
      of which is most likely related to loss from the Antarctic ice sheet mass around
      5000 years before present. In contrast, the occurrence of large and flat
      microatolls indicates periods of significant sea-level stability lasting up to
      ~300 years.

PMID- 29348405
TI  - Directional sound beam emission from a configurable compact multi-source system.
AB  - We propose to achieve efficient emission of highly directional sound beams from
      multiple monopole sources embedded in a subwavelength enclosure. Without the
      enclosure, the emitted sound fields have an indistinguishable or omnidirectional
      radiation directivity in far fields. The strong directivity formed in the
      presence of the enclosure is attributed to interference of sources under
      degenerate Mie resonances in the enclosure of anisotropic property. Our numerical
      simulations of sound emission from the sources demonstrate the radiation of a
      highly directed sound beam of unidirectional or bidirectional patterns, depending
      on how the sources are configured inside the enclosure. Our scheme, if achieved,
      can solve the challenging problem of poor directivity of a subwavelength sound
      system, and can guide beam forming and collimation by miniaturized devices.

PMID- 29348404
TI  - Crystal structure of an assembly intermediate of respiratory Complex II.
AB  - Flavin is covalently attached to the protein scaffold in ~10% of flavoenzymes.
      However, the mechanism of covalent modification is unclear, due in part to
      challenges in stabilizing assembly intermediates. Here, we capture the structure
      of an assembly intermediate of the Escherichia coli Complex II (quinol:fumarate
      reductase (FrdABCD)). The structure contains the E. coli FrdA subunit bound to
      covalent FAD and crosslinked with its assembly factor, SdhE. The structure
      contains two global conformational changes as compared to prior structures of the
      mature protein: the rotation of a domain within the FrdA subunit, and the
      destabilization of two large loops of the FrdA subunit, which may create a tunnel
      to the active site. We infer a mechanism for covalent flavinylation. As supported
      by spectroscopic and kinetic analyses, we suggest that SdhE shifts the
      conformational equilibrium of the FrdA active site to disfavor succinate/fumarate
      interconversion and enhance covalent flavinylation.

PMID- 29348406
TI  - Active State Organization of Spontaneous Behavioral Patterns.
AB  - We report the development and validation of a principled analytical approach to
      reveal the manner in which diverse mouse home cage behaviors are organized. We
      define and automate detection of two mutually-exclusive low-dimensional
      spatiotemporal units of behavior: "Active" and "Inactive" States. Analyses of
      these features using a large multimodal 16-strain behavioral dataset provide a
      series of novel insights into how feeding, drinking, and movement behaviors are
      coordinately expressed in Mus Musculus. Moreover, we find that patterns of Active
      State expression are exquisitely sensitive to strain, and classical supervised
      machine learning incorporating these features provides 99% cross-validated
      accuracy in genotyping animals using behavioral data alone. Altogether, these
      findings advance understanding of the organization of spontaneous behavior and
      provide a high-throughput phenotyping strategy with wide applicability to
      behavioral neuroscience and animal models of disease.

PMID- 29348407
TI  - Error-related cardiac response as information for visibility judgements.
AB  - Interoception provides information about the saliency of external or internal
      sensory events and thus may inform perceptual decision-making. Error in
      performance is an example of a motivationally significant internal event that
      evokes autonomic nervous system response resembling the orienting response: heart
      rate deceleration, increased skin conductance response, and pupil dilation. Here,
      we investigate whether error-related cardiac activity may serve as a source of
      information when making metacognitive judgments in an orientation discrimination
      backward masking task. In the first experiment, we found that the heart
      accelerates less after an incorrect stimuli discrimination than after a correct
      one. Moreover, this difference becomes more pronounced with increasing subjective
      visibility of the stimuli. In the second experiment, this accuracy-dependent
      pattern of cardiac activity was found only when participants listened to their
      own heartbeats, but not someone else's. We propose that decision accuracy coded
      in cardiac activity may be fed as a cue to subjective visibility judgments.

PMID- 29348408
TI  - NIPBL+/- haploinsufficiency reveals a constellation of transcriptome disruptions
      in the pluripotent and cardiac states.
AB  - Cornelia de Lange syndrome (CdLS) is a complex disorder with multiple structural
      and developmental defects caused by mutations in structural and regulatory
      proteins involved in the cohesin complex. NIPBL, a cohesin regulatory protein,
      has been identified as a critical protein responsible for the orchestration of
      transcriptomic regulatory networks necessary for embryonic development. Mutations
      in NIPBL are responsible for the majority of cases of CdLS. Through RNA
      sequencing of human induced pluripotent stem cells and in vitro-derived
      cardiomyocytes, we identified hundreds of mRNAs, pseudogenes, and non-coding RNAs
      with altered expression in NIPBL+/- patient-derived cells. We demonstrate that
      NIPBL haploinsufficiency leads to upregulation of gene sets identified in
      functions related to nucleosome, chromatin assembly, RNA modification and
      downregulation of Wnt signaling, cholesterol biosynthesis and vesicular transport
      in iPSC and cardiomyocytes. Mutations in NIPBL result in the dysregulation of
      many genes responsible for normal heart development likely resulting in the
      variety of structural cardiac defects observed in the CdLS population.

PMID- 29348409
TI  - Artificial selection for improved energy efficiency is reaching its limits in
      broiler chickens.
AB  - Modern broiler chickens are a major animal husbandry success story, both in terms
      of efficient resource utilisation and environmental sustainability. However,
      continuing artificial selection for both efficiency and rapid growth will be
      subject to both biological limits and animal welfare concerns. Using a novel
      analytical energy flow modelling approach, we predict how far such selection can
      go, given the biological limits of bird energy intake and partitioning of energy.
      We find that the biological potential for further improvements in efficiency, and
      hence environmental impact reduction, is minimal relative to past progress
      already made via artificial selection. An alternative breeding strategy to
      produce slower-growing birds to meet new welfare standards increases
      environmental burdens, compared to current birds. This unique analytic approach
      provides biologically sound guidelines for strategic planning of sustainable
      broiler production.

PMID- 29348410
TI  - Oxidative stress via inhibition of the mitochondrial electron transport and Nrf-2
      mediated anti-oxidative response regulate the cytotoxic activity of plumbagin.
AB  - Plumbagin, an anti-cancer agent, is toxic to cells of multiple species. We
      investigated if plumbagin targets conserved biochemical processes. Plumbagin
      induced DNA damage and apoptosis in cells of diverse mutational background with
      comparable potency. A 3-5 fold increase in intracellular oxygen radicals occurred
      in response to plumbagin. Neutralization of the reactive oxygen species by N
      acetylcysteine blocked apoptosis, indicating a central role for oxidative stress
      in plumbagin-mediated cell death. Plumbagin docks in the ubiquinone binding sites
      (Q0 and Qi) of mitochondrial complexes I-III, the major sites for oxygen
      radicals. Plumbagin decreased oxygen consumption rate, ATP production and optical
      redox ratio (NAD(P)H/FAD) indicating interference with electron transport
      downstream of mitochondrial Complex II. Oxidative stress induced by plumbagin
      triggered an anti-oxidative response via activation of Nrf2. Plumbagin and the
      Nrf2 inhibitor, brusatol, synergized to inhibit cell proliferation. These data
      indicate that while inhibition of electron transport is the conserved mechanism
      responsible for plumbagin's chemotoxicity, activation of Nrf2 is the resulting
      anti-oxidative response that allows plumbagin to serve as a chemopreventive
      agent. This study provides the basis for designing potent and selective plumbagin
      analogs that can be coupled with suitable Nrf2 inhibitors for chemotherapy or
      administered as single agents to induce Nrf2-mediated chemoprevention.

PMID- 29348411
TI  - In vivo Microscopic Photoacoustic Spectroscopy for Non-Invasive Glucose
      Monitoring Invulnerable to Skin Secretion Products.
AB  - Photoacoustic spectroscopy has been shown to be a promising tool for non-invasive
      blood glucose monitoring. However, the repeatability of such a method is
      susceptible to changes in skin condition, which is dependent on hand washing and
      drying due to the high absorption of infrared excitation light to the skin
      secretion products or water. In this paper, we present a method to meet the
      challenges of mid-infrared photoacoustic spectroscopy for non-invasive glucose
      monitoring. By obtaining the microscopic spatial information of skin during the
      spectroscopy measurement, the skin region where the infrared spectra is
      insensitive to skin condition can be locally selected, which enables reliable
      prediction of the blood glucose level from the photoacoustic spectroscopy
      signals. Our raster-scan imaging showed that the skin condition for in vivo
      spectroscopic glucose monitoring had significant inhomogeneities and large
      variability in the probing area where the signal was acquired. However, the
      selective localization of the probing led to a reduction in the effects of
      variability due to the skin secretion product. Looking forward, this technology
      has broader applications not only in continuous glucose monitoring for diabetic
      patient care, but in forensic science, the diagnosis of malfunctioning sweat
      pores, and the discrimination of tumors extracted via biopsy.

PMID- 29348412
TI  - Influence of autophagy on acute kidney injury in a murine cecal ligation and
      puncture sepsis model.
AB  - The role of autophagy in the maintenance of renal homeostasis during sepsis is
      not well understood. We therefore aimed to determine the influence of autophagy
      on kidney during sepsis using a murine sepsis model, i.e. cecal ligation and
      puncture (CLP). In CLP treated animals, the number of autolysosomes observed by
      electron microscopy increased over time. The number of autophagosomes in CLP
      animals decreased relative sham operated controls at 24 hrs after CLP, indicating
      that autophagy flux is already diminishing by that time. Moreover, CLP induced an
      increase in LC3-II/LC3-I ratio at 6-8 hrs, demonstrated in western blots, as well
      as an increase in GFP-LC3 dots at 6-8 hrs and 24 hrs, using immunofluorescence
      and anti-LC3 and LAMP1 antibodies on tissue sections from GFP-LC3 transgenic
      mice. LC3-II/LC3-I ratio and the number of co-localized GFP-LC3 dots and LAMP1
      signals (GFP LC3 + LAMP1 dots) in CLP mice at 24 hrs were significantly reduced
      compared with data obtained at 6-8 hrs. Notably, acceleration of autophagy by
      rapamycin resulted in improvement of renal function that was associated with
      improvement in the histologic severity of tubular epithelial injury in CLP
      treated animals. Autophagy in the kidney was significantly slowed in the kidney
      during the acute phase of sepsis; nonetheless, autophagy in kidney appears to
      play a protective role against sepsis.

PMID- 29348413
TI  - Synthesis of Luminescent Carbon Dots with Ultrahigh Quantum Yield and Inherent
      Folate Receptor-Positive Cancer Cell Targetability.
AB  - Carbon dots (CDs) have a wide range of applications in chemical, physical and
      biomedical research fields. We are particularly interested in the use of CDs as
      fluorescence nanomaterials for targeted tumor cell imaging. One of the important
      aspects of success is to enhance the fluorescence quantum yields (QY) of CDs as
      well as increase their targetability to tumor cells. However, most of the
      reported CDs are limited by relative low QY. In the current study, for the first
      time, one-step synthesis of highly luminescent CDs by using folic acid (FA) as
      single precursor was obtained in natural water through hydrothermal method. The
      as-prepared CDs exhibited QY as high as 94.5% in water, which is even higher than
      most of organic fluorescent dyes. The obtained CDs showed excellent
      photoluminescent activity, high photostability and favorable biocompatibility.
      The FA residuals in CDs led to extraordinary targetability to cancer cells and
      promoted folate receptor-mediated cellular uptake successfully, which holds a
      great potential in biological and bioimaging studies.

PMID- 29348414
TI  - MicroRNA-146a-5p attenuates irradiation-induced and LPS-induced hepatic stellate
      cell activation and hepatocyte apoptosis through inhibition of TLR4 pathway.
AB  - Elevated toll-like receptor 4 (TLR4) expression is associated with a high risk of
      radiation-induced liver disease (RILD). MicroRNA (miR)-146a-5p is a key regulator
      of lipopolysaccharide (LPS)/TLR4 signaling, but its role in modulation of RILD
      remains unclear. Here, we found that irradiation and LPS stimulation induced TLR4
      and miR-146a-5p expression in the human hepatic stellate cell (HSC) line LX2.
      Ectopic expression of miR-146a-5p in LX2 inhibited irradiation-induced and LPS
      induced pro-inflammatory cytokine secretion and cell proliferation, and promoted
      cell apoptosis by down-regulating the expression levels of TLR4, interleukin-1
      receptor associated kinase 1 (IRAK1), tumor necrosis factor receptor associated
      factor 6 (TRAF6) and phosphorylation of nuclear factor-kappa B. In addition, the
      culture medium from the irradiated and LPS-stimulated HSCs transfected with miR
      146a-5p significantly attenuated apoptosis in irradiated hepatocytes.
      Overexpression of miR-146a-5p reduced alpha-smooth muscle actin production in
      irradiated and LPS-stimulated LX2 cells, which was associated with inhibition of
      TRAF6-mediated JNK and Smad2 phosphorylation. Knockdown of TRAF6 or IRAK1
      mimicked the effects of miR-146a-5p on HSC function. Furthermore, miR-146a-5p
      treatment alleviated irradiation-induced and endotoxin-induced hepatic
      inflammatory response and fibrogenesis in mice through inhibition of the TLR4
      signaling pathway. Collectively, this study reveals the anti-pro-inflammatory and
      anti-fibrotic effects of miR-146a-5p on liver injury, and suggests a potential
      application of miR-146a-5p in the therapeutic prevention of RILD.

PMID- 29348415
TI  - Trends in Fetal Growth Between 2000 to 2014 in Singleton Live Births from Israel.
AB  - Trends in birthweight and abnormal fetal growth, namely term low birthweight
      (LBW), macrosomia, small-for-gestational age (SGA) and large-for-gestational age
      (LGA), are important indicators of changes in the health of populations. We
      performed this epidemiological study to evaluate these trends among 2,039,415
      singleton live births from Israel over a period of 15 years. Birth certificate
      data was obtained from the Ministry of Health. Multivariable linear and logistic
      regression models were used to evaluate crude and adjusted estimates compared to
      the baseline of 2000 and polynomial trends. During the study period we observed a
      significant decrease in the rates of infants born SGA and LGA (10.7% to 9.2%,
      10.2% to 9.6% respectively). After adjustment, based on the imputed data set,
      term mean birthweight increased by 6.0 grams (95% CI: 2.9, 9.1), and term LBW
      odds decreased by 19% in 2014 compared to 2000 (adj ORs: 0.81; 95% CI: 0.77,
      0.85). Significant decreases were also observed for adjusted SGA, LGA and
      macrosomia rates. The decrease in abnormal fetal growth rates were not entirely
      explained by changes in sociodemographic characteristics or gestational age and
      may imply real improvement in child intrauterine growth in Israel during the last
      15 years, especially in the Jewish population.

PMID- 29348416
TI  - Magneto Acoustic Spin Hall Oscillators.
AB  - This paper introduces a novel oscillator that combines the tunability of spin
      Hall-driven nano oscillators with the high quality factor (Q) of high overtone
      bulk acoustic wave resonators (HBAR), integrating both reference and tunable
      oscillators on the same chip with CMOS. In such magneto acoustic spin Hall (MASH)
      oscillators, voltage oscillations across the magnetic tunnel junction (MTJ) that
      arise from a spin-orbit torque (SOT) are shaped by the transmission response of
      the HBAR that acts as a multiple peak-bandpass filter and a delay element due to
      its large time constant, providing delayed feedback. The filtered voltage
      oscillations can be fed back to the MTJ via (a) strain, (b) current, or (c)
      magnetic field. We develop a SPICE-based circuit model by combining
      experimentally benchmarked models including the stochastic Landau-Lifshitz
      Gilbert (sLLG) equation for magnetization dynamics and the Butterworth Van Dyke
      (BVD) circuit for the HBAR. Using the self-consistent model, we project up to
      ~50X enhancement in the oscillator linewidth with Q reaching up to 52825 at 3
      GHz, while preserving the tunability by locking the STNO to the nearest high Q
      peak of the HBAR. We expect that our results will inspire MEMS-based solutions to
      spintronic devices by combining attractive features of both fields for a variety
      of applications.

PMID- 29348417
TI  - Identification of a membrane-less compartment regulating invadosome function and
      motility.
AB  - Depletion of liprin-alpha1, ERC1 or LL5 scaffolds inhibits extracellular matrix
      degradation by invasive cells. These proteins co-accumulate near invadosomes in
      NIH-Src cells, identifying a novel invadosome-associated compartment distinct
      from the core and adhesion ring of invadosomes. Depletion of either protein
      perturbs the organization of invadosomes without influencing the recruitment of
      MT1-MMP metalloprotease. Liprin-alpha1 is not required for de novo formation of
      invadosomes after their disassembly by microtubules and Src inhibitors, while its
      depletion inhibits invadosome motility, thus affecting matrix degradation.
      Fluorescence recovery after photobleaching shows that the invadosome-associated
      compartment is dynamic, while correlative light immunoelectron microscopy
      identifies bona fide membrane-free invadosome-associated regions enriched in
      liprin-alpha1, which is virtually excluded from the invadosome core. The results
      indicate that liprin-alpha1, LL5 and ERC1 define a novel dynamic membrane-less
      compartment that regulates matrix degradation by affecting invadosome motility.

PMID- 29348418
TI  - A Novel Modeling in Mathematical Biology for Classification of Signal Peptides.
AB  - The molecular structure of macromolecules in living cells is ambiguous unless we
      classify them in a scientific manner. Signal peptides are of vital importance in
      determining the behavior of newly formed proteins towards their destined path in
      cellular and extracellular location in both eukaryotes and prokaryotes. In the
      present research work, a novel method is offered to foreknow the behavior of
      signal peptides and determine their cleavage site. The proposed model employs
      neural networks using isolated sets of prokaryote and eukaryote primary
      sequences. Protein sequences are classified as secretory or non-secretory in
      order to investigate secretory proteins and their signal peptides. In comparison
      with the previous prediction tools, the proposed algorithm is more rigorous, well
      organized, significantly appropriate and highly accurate for the examination of
      signal peptides even in extensive collection of protein sequences.

PMID- 29348419
TI  - Dysbindin links presynaptic proteasome function to homeostatic recruitment of low
      release probability vesicles.
AB  - Here we explore the relationship between presynaptic homeostatic plasticity and
      proteasome function at the Drosophila neuromuscular junction. First, we
      demonstrate that the induction of homeostatic plasticity is blocked after
      presynaptic proteasome perturbation. Proteasome inhibition potentiates release
      under baseline conditions but not during homeostatic plasticity, suggesting that
      proteasomal degradation and homeostatic plasticity modulate a common pool of
      vesicles. The vesicles that are regulated by proteasome function and recruited
      during homeostatic plasticity are highly EGTA sensitive, implying looser Ca2+
      influx-release coupling. Similar to homeostatic plasticity, proteasome
      perturbation enhances presynaptic Ca2+ influx, readily-releasable vesicle pool
      size, and does not potentiate release after loss of specific homeostatic
      plasticity genes, including the schizophrenia-susceptibility gene dysbindin.
      Finally, we provide genetic evidence that Dysbindin levels regulate the access to
      EGTA-sensitive vesicles. Together, our data suggest that presynaptic protein
      degradation opposes the release of low-release probability vesicles that are
      potentiated during homeostatic plasticity and whose access is controlled by
      dysbindin.

PMID- 29348420
TI  - Gender-related differences in heart failure with preserved ejection fraction.
AB  - Heart failure with preserved ejection fraction (HFpEF) affects more women than
      men, suggesting gender to play a major role in disease evolution. However,
      studies investigating gender differences in HFpEF are limited. In the present
      study we aimed to describe gender differences in a well-characterized HFpEF
      cohort. Consecutive HFpEF patients underwent invasive hemodynamic assessment,
      cardiac magnetic resonance imaging and exercise testing. Study endpoints were:
      cardiac death, a combined endpoint of HF hospitalization or cardiac death and all
      cause death. 260 HFpEF patients were prospectively enrolled. Men were more
      compromised with regard to exercise capacity and had significantly more co
      morbidities. Men had more pronounced pulmonary vascular disease with higher
      diastolic pressure gradients and a lower right ventricular EF. During follow-up,
      9.2% experienced cardiac death, 33.5% the combined endpoint and 17.3% all-cause
      death. Male gender was independently associated with cardiac death, but neither
      with the combined endpoint nor with all-cause mortality. We detected clear gender
      differences in HFpEF patients. Cardiac death was more common among men, but not
      all-cause death. While men are more prone to develop a right heart phenotype and
      die from HFpEF, women are more likely to die with HFpEF.

PMID- 29348421
TI  - Patients over 40 years old with precursor T-cell lymphoblastic lymphoma have
      different prognostic factors comparing to the youngers.
AB  - This study aimed to analyze the clinical characteristics and prognostic factors
      of patients, divided into over 40-year-old group or not, with precursor T-cell
      lymphoblastic lymphoma (Pre-T-LBL). Based on the retrospective analysis of the
      clinical data of 59 patients with Pre-T-LBL during the period from December 2010
      to December 2015, albumin level, anemia, pleural or pericardial effusion,
      protocol, therapy response, mediastinal mass, lactate dehydrogenase (LDH), and
      international prognostic index (IPI) or age-adjusted international prognostic
      index (aaIPI) were summarized. For patients aged <40 years, factors correlating
      with poor progression-free survival (PFS) were pleural or pericardial effusion,
      regimen, albumin level and therapy response. Pleural or pericardial effusion,
      aaIPI score, regimen, LDH increased, albumin level, therapy response and
      mediastinal mass were all related with poor overall survival (OS). In the
      patients aged >=40 years, only anemia associated with PFS. However, anemia,
      involvement of bone marrow and therapeutic response were all related with poor
      OS. In conclusion, the patients with Pre-T-LBL are characterized by a low
      incidence and bad prognosis. Different prognostic factors can be discovered for
      patients over 40-year-old with Pre-T-LBL comparing to the youngers. New
      prognostic evaluation factors should be explored for patients >=40 years old.

PMID- 29348422
TI  - Individuals with depressive tendencies experience difficulty in forgetting
      negative material: two mechanisms revealed by ERP data in the directed forgetting
      paradigm.
AB  - Although previous studies have shown that individuals with depressive tendencies
      have deficits in forgetting negative material, the detailed underlying neural
      mechanisms have not been elucidated. This study examined the intentional
      forgetting of negative and neutral material in individuals with depressive
      tendencies in two phases. In the study phase, the participants performed a
      directed forgetting task, where a total of 320 words were presented to them, each
      followed by an instructive cue to forget or remember the previously presented
      word. Subsequently, in the memory recognition test phase, the participants
      completed the "old or new discrimination task". The results indicated that
      individuals with depressive tendencies had difficulties suppressing the memory
      encoding of negative words, while the suppression of memory encoding of neutral
      words was relatively intact. Moreover, individuals with depressive tendencies
      displayed enhanced word-evoked P2 and late positive potential for negative items,
      as well as enhanced cue-evoked P1 and N2 for the negative items that were
      required to be forgotten, as compared to individuals without depressive
      tendencies. Based on these results, we propose two mechanisms that may contribute
      to the failure of forgetting negative material in mild depression: (1)
      inefficient memory suppression and early selective attention, and (2) excessive
      preliminary processing.

PMID- 29348423
TI  - A tissue-mimetic nano-fibrillar hybrid injectable hydrogel for potential soft
      tissue engineering applications.
AB  - While collagen type I (Col-I) is commonly used as a structural component of
      biomaterials, collagen type III (Col-III), another fibril forming collagen
      ubiquitous in many soft tissues, has not previously been used. In the present
      study, the novel concept of an injectable hydrogel with semi-interpenetrating
      polymeric networks of heterotypic collagen fibrils, with tissue-specific Col-III
      to Col-I ratios, in a glycol-chitosan matrix was investigated. Col-III was
      introduced as a component of the novel hydrogel, inspired by its co-presence with
      Col-I in many soft tissues, its influence on the Col-I fibrillogenesis in terms
      of diameter and mechanics, and its established role in regulating scar formation.
      The hydrogel has a nano-fibrillar porous structure, and is mechanically stable
      under continuous dynamic stimulation. It was found to provide a longer half-life
      of about 35 days than similar hyaluronic acid-based hydrogels, and to support
      cell implantation in terms of viability, metabolic activity, adhesion and
      migration. The specific case of pure Col-III fibrils in a glycol-chitosan matrix
      was investigated. The proposed hydrogels meet many essential requirements for
      soft tissue engineering applications, particularly for mechanically challenged
      tissues such as vocal folds and heart valves.

PMID- 29348424
TI  - Intraocular inflammatory cytokines in patients with neovascular age-related
      macular degeneration before and after initiation of intravitreal injection of
      anti-VEGF inhibitor.
AB  - Age-related macular degeneration (AMD) is a cause of blindness in people older
      than 50 years. Accumulating evidence indicates the involvement of systemic and
      local inflammation in the pathogenesis and progression of AMD. Aflibercept is an
      anti-vascular endothelial growth factor (VEGF) inhibitor, and intravitreal
      injection of aflibercept (IVA) is the approved treatments of neovascular AMD
      (nAMD), but the effect on inflammatory response remains unclear. The aim of our
      study was to investigate the profiles of inflammatory cytokines in the aqueous
      humor of nAMD patients before and after initiation of IVA. In nAMD patients, IP
      10 level was significantly higher and IL-6 level was significantly lower compared
      with those of cataract patients as controls. Logistic regression analysis
      identified IP-10 as a positive factor and IL-6 a negative factor associated with
      the pathogenesis of nAMD. In addition, IP-10 level correlated positively with the
      mean thickness of macula in the central 1-mm diameter circle. After initiation of
      IVA, IP-10 level was further elevated, and correlated negatively with VEGF level.
      These data suggest that IP-10 plays a critical role as an antiangiogenic factor
      and at the same time an inflammatory factor in the pathogenesis and
      pathophysiology of nAMD eyes at onset and after IVA initiation.

PMID- 29348425
TI  - Serum uric acid levels in patients with amyotrophic lateral sclerosis: a meta
      analysis.
AB  - The pathogenic mechanism of ALS remains unclear. However, increasing evidence has
      indicated that uric acid (UA) may play a protective role in the pathogenesis of
      ALS. The aim of this study was to evaluate the association between serum UA
      levels and ALS. A comprehensive literature search in PubMed, Embase, Web of
      Science, and Cochrane Library was conducted up to 31st August, 2017, using
      keywords. A random-effects model or fixed-effects model was used to calculate the
      pooled estimate according to the inter-group heterogeneity. Finally, we
      indentified 8 case-control and 3 cohort studies. The results indicated that
      patients with ALS had significant decreased levels of serum UA compared to
      healthy controls (standardized mean difference (SMD) = -0.72, 95% CI [-0.98,
      0.46], P < 0.001). Increased serum UA levels were associated with lower all-cause
      mortality risk among ALS patients (risk ratio (RR) = 0.70, 95% CI [0.57, 0.87], P
      = 0.001). To summarize, there is an inverse association between serum UA levels
      and risk of death among ALS patients. Randomized controlled trials with high
      quality are required to elucidate the role of UA on ALS.

PMID- 29348426
TI  - One protein, different cell fate: the differential outcome of depleting GRP75
      during oxidative stress in neurons.

PMID- 29348427
TI  - Multi-stage volcanic island flank collapses with coeval explosive caldera-forming
      eruptions.
AB  - Volcanic flank collapses and explosive eruptions are among the largest and most
      destructive processes on Earth. Events at Mount St. Helens in May 1980
      demonstrated how a relatively small (<5 km3) flank collapse on a terrestrial
      volcano could immediately precede a devastating eruption. The lateral collapse of
      volcanic island flanks, such as in the Canary Islands, can be far larger (>300
      km3), but can also occur in complex multiple stages. Here, we show that
      multistage retrogressive landslides on Tenerife triggered explosive caldera
      forming eruptions, including the Diego Hernandez, Guajara and Ucanca caldera
      eruptions. Geochemical analyses were performed on volcanic glasses recovered from
      marine sedimentary deposits, called turbidites, associated with each individual
      stage of each multistage landslide. These analyses indicate only the lattermost
      stages of subaerial flank failure contain materials originating from respective
      coeval explosive eruption, suggesting that initial more voluminous submarine
      stages of multi-stage flank collapse induce these aforementioned explosive
      eruption. Furthermore, there are extended time lags identified between the
      individual stages of multi-stage collapse, and thus an extended time lag between
      the initial submarine stages of failure and the onset of subsequent explosive
      eruption. This time lag succeeding landslide-generated static decompression has
      implications for the response of magmatic systems to un-roofing and poses a
      significant implication for ocean island volcanism and civil emergency planning.

PMID- 29348428
TI  - Evaluation of quantitative parameters for distinguishing pheochromocytoma from
      other adrenal tumors.
AB  - Adrenal tumors are increasingly found incidentally during imaging examinations.
      It is important to distinguish pheochromocytomas from other adrenal tumors
      because of the risk of hypertensive crisis. Although catecholamines and their
      metabolites are generally used to diagnose pheochromocytoma, false-positive test
      results are common. An effective screening method to distinguish pheochromocytoma
      from adrenal incidentalomas is needed. We analyzed 297 consecutive patients with
      adrenal incidentalomas. Our findings included 162 non-functioning tumors, 47
      aldosterone-producing adenomas, 26 metastases, 22 cases of subclinical Cushing's
      syndrome, 21 pheochromocytomas, 12 cases of Cushing's syndrome, and 7
      adrenocortical cancers. We checked quantitative parameters such as age, blood,
      and urine catecholamines and their metabolites, neuron-specific enolase, size and
      computed tomography (CT) attenuation values. Among catecholamine-related
      parameters, the sum of urine metanephrine and normetanephrine (urineMNM) levels
      produced the highest area under the receiver operating characteristic curve
      regarding discrimination of pheochromocytoma from other lesions. Size and CT
      attenuation values also differed significantly. However, size was correlated with
      catecholamine levels. CT attenuation was not correlated with other factors. The
      optimal thresholds were 19 Hounsfield units (HU) for CT attenuation (sensitivity,
      100%; specificity, 60%) and 0.43 mg/24 h for urineMNM (sensitivity, 89%;
      specificity, 96%). No pheochromocytomas were evident when CT attenuation values
      were under 19 HU. Even in adrenal tumors with CT attenuation values >= 19 HU,
      when urineMNM was < 0.43 mg/24 h, the frequency of pheochromocytoma was only
      4.3%, when urineMNM was >= 0.43 mg/24 h, the frequency of pheochromocytoma was
      93% and when urineMNM was > 0.77 mg/24 h the frequency of pheochromocytoma was
      100%. CT attenuation value and urineMNM represented the most useful combination
      for diagnosis of pheochromocytoma.

PMID- 29348429
TI  - Structural basis of trans-synaptic interactions between PTPdelta and SALMs for
      inducing synapse formation.
AB  - Synapse formation is triggered by trans-synaptic interactions of cell adhesion
      molecules, termed synaptic organizers. Three members of type-II receptor protein
      tyrosine phosphatases (classified as type-IIa RPTPs; PTPdelta, PTPsigma and LAR)
      are known as presynaptic organizers. Synaptic adhesion-like molecules (SALMs)
      have recently emerged as a family of postsynaptic organizers. Although all five
      SALM isoforms can bind to the type-IIa RPTPs, only SALM3 and SALM5 reportedly
      have synaptogenic activities depending on their binding. Here, we report the
      crystal structures of apo-SALM5, and PTPdelta-SALM2 and PTPdelta-SALM5 complexes.
      The leucine-rich repeat (LRR) domains of SALMs interact with the second
      immunoglobulin-like (Ig) domain of PTPdelta, whereas the Ig domains of SALMs
      interact with both the second and third Ig domains of PTPdelta. Unexpectedly, the
      structures exhibit the LRR-mediated 2:2 complex. Our synaptogenic co-culture
      assay using site-directed SALM5 mutants demonstrates that presynaptic
      differentiation induced by PTPdelta-SALM5 requires the dimeric property of SALM5.

PMID- 29348430
TI  - Rotator side chains trigger cooperative transition for shape and function memory
      effect in organic semiconductors.
AB  - Martensitic transition is a solid-state phase transition involving cooperative
      movement of atoms, mostly studied in metallurgy. The main characteristics are low
      transition barrier, ultrafast kinetics, and structural reversibility. They are
      rarely observed in molecular crystals, and hence the origin and mechanism are
      largely unexplored. Here we report the discovery of martensitic transition in
      single crystals of two different organic semiconductors. In situ microscopy,
      single-crystal X-ray diffraction, Raman and nuclear magnetic resonance
      spectroscopy, and molecular simulations combined indicate that the rotating bulky
      side chains trigger cooperative transition. Cooperativity enables shape memory
      effect in single crystals and function memory effect in thin film transistors. We
      establish a molecular design rule to trigger martensitic transition in organic
      semiconductors, showing promise for designing next-generation smart
      multifunctional materials.

PMID- 29348431
TI  - A synthetic combinatorial approach to disabling deviant Hedgehog signaling.
AB  - Mutations in components of the Hedgehog (HH) signal transduction pathway are
      found in the majority of basal cell carcinoma (BCC) and medulloblastoma
      incidents. Cancerous cells with intrinsic or acquired resistance to antagonists
      targeting the seven transmembrane effector Smoothened (SMO) frequently invoke
      alternative mechanisms for maintaining deviant activity of the GLI DNA binding
      proteins. Here we introduce a chemical agent that simultaneously achieves
      inhibition of SMO and GLI activity by direct targeting of the SMO heptahelical
      domain and the GLI-modifying enzymes belonging to the histone deacetylase (HDAC)
      family. We demonstrate a small molecule SMO-HDAC antagonist (IHR-SAHA) retains
      inhibitory activity for GLI transcription induced by SMO-dependent and 
      independent mechanisms frequently associated with cancer biogenesis. Synthetic
      combinatorial therapeutic agents such as IHR-SAHA that a priori disable cancer
      drivers and anticipated mechanisms of drug resistance could extend the duration
      of disease remission, and provide an alternative clinical development path for
      realizing combinatorial therapy modalities.

PMID- 29348433
TI  - Speciation of common Gram-negative pathogens using a highly multiplexed high
      resolution melt curve assay.
AB  - The identification of the bacterial species responsible for an infection remains
      an important step for the selection of antimicrobial therapy. Gram-negative
      bacteria are an important source of hospital and community acquired infections
      and frequently antimicrobial resistant. Speciation of bacteria is typically
      carried out by biochemical profiling of organisms isolated from clinical
      specimens, which is time consuming and delays the initiation of tailored
      treatment. Whilst molecular methods such as PCR have been used, they often
      struggle with the challenge of detecting and discriminating a wide range of
      targets. High resolution melt analysis is an end-point qPCR detection method that
      provides greater multiplexing capability than probe based methods. Here we report
      the design of a high resolution melt analysis assay for the identification of six
      common Gram-negative pathogens; Escherichia coli, Klebsiella pneumoniae,
      Klebsiella oxytoca, Pseudomonas aeruginosa, Salmonella Sp, and Acinetobacter
      baumannii, and a generic Gram-negative specific 16S rRNA control. The assay was
      evaluated using a well characterised collection of 113 clinically isolated Gram
      negative bacteria. The agreement between the HRM assay and the reference test of
      PCR and sequencing was 98.2% (Kappa 0.96); the overall sensitivity and
      specificity of the assay was 97.1% (95% CI: 90.1-99.7%) and 100% (95% CI: 91.78
      100%) respectively.

PMID- 29348432
TI  - Genome-wide association study of self-reported food reactions in Japanese
      identifies shrimp and peach specific loci in the HLA-DR/DQ gene region.
AB  - Food allergy is an increasingly important health problem in the world. Several
      genome-wide association studies (GWAS) focused on European ancestry samples have
      identified food allergy-specific loci in the HLA class II region. We conducted
      GWAS of self-reported reactivity with common foods using the data from 11011
      Japanese women and identified shrimp and peach allergy-specific loci in the HLA
      DR/DQ gene region tagged by rs74995702 (P = 6.30 * 10-17, OR = 1.91) and
      rs28359884 (P = 2.3 * 10-12, OR = 1.80), respectively. After HLA imputation using
      a Japanese population-specific reference, the most strongly associated haplotype
      was HLA-DRB1*04:05-HLA-DQB1*04:01 for shrimp allergy (P = 3.92 * 10-19, OR =
      1.99) and HLA-DRB1*09:01-HLA-DQB1*03:03 for peach allergy (P = 1.15 * 10-7, OR =
      1.68). Additionally, both allergies' associated variants were eQTLs for several
      HLA genes, with HLA-DQA2 the single eQTL gene shared between the two traits. Our
      study suggests that allergy to certain foods may be related to genetic
      differences that tag both HLA alleles having particular epitope binding
      specificities as well as variants modulating expression of particular HLA genes.
      Investigating this further could increase our understanding of food allergy
      aetiology and potentially lead to better therapeutic strategies for allergen
      immunotherapies.

PMID- 29348436
TI  - High-throughput analysis using non-depletive SPME: challenges and applications to
      the determination of free and total concentrations in small sample volumes.
AB  - In vitro high-throughput non-depletive quantitation of chemicals in biofluids is
      of growing interest in many areas. Some of the challenges facing researchers
      include the limited volume of biofluids, rapid and high-throughput sampling
      requirements, and the lack of reliable methods. Coupled to the above, growing
      interest in the monitoring of kinetics and dynamics of miniaturized biosystems
      has spurred the demand for development of novel and revolutionary methodologies
      for analysis of biofluids. The applicability of solid-phase microextraction
      (SPME) is investigated as a potential technology to fulfill the aforementioned
      requirements. As analytes with sufficient diversity in their physicochemical
      features, nicotine, N,N-Diethyl-meta-toluamide, and diclofenac were selected as
      test compounds for the study. The objective was to develop methodologies that
      would allow repeated non-depletive sampling from 96-well plates, using 100 uL of
      sample. Initially, thin film-SPME was investigated. Results revealed substantial
      depletion and consequent disruption in the system. Therefore, new ultra-thin
      coated fibers were developed. The applicability of this device to the described
      sampling scenario was tested by determining the protein binding of the analytes.
      Results showed good agreement with rapid equilibrium dialysis. The presented
      method allows high-throughput analysis using small volumes, enabling fast
      reliable free and total concentration determinations without disruption of system
      equilibrium.

PMID- 29348435
TI  - Macrophage sensing of single-walled carbon nanotubes via Toll-like receptors.
AB  - Carbon-based nanomaterials including carbon nanotubes (CNTs) have been shown to
      trigger inflammation. However, how these materials are 'sensed' by immune cells
      is not known. Here we compared the effects of two carbon-based nanomaterials,
      single-walled CNTs (SWCNTs) and graphene oxide (GO), on primary human monocyte
      derived macrophages. Genome-wide transcriptomics assessment was performed at sub
      cytotoxic doses. Pathway analysis of the microarray data revealed pronounced
      effects on chemokine-encoding genes in macrophages exposed to SWCNTs, but not in
      response to GO, and these results were validated by multiplex array-based
      cytokine and chemokine profiling. Conditioned medium from SWCNT-exposed cells
      acted as a chemoattractant for dendritic cells. Chemokine secretion was reduced
      upon inhibition of NF-kappaB, as predicted by upstream regulator analysis of the
      transcriptomics data, and Toll-like receptors (TLRs) and their adaptor molecule,
      MyD88 were shown to be important for CCL5 secretion. Moreover, a specific role
      for TLR2/4 was confirmed by using reporter cell lines. Computational studies to
      elucidate how SWCNTs may interact with TLR4 in the absence of a protein corona
      suggested that binding is guided mainly by hydrophobic interactions. Taken
      together, these results imply that CNTs may be 'sensed' as pathogens by immune
      cells.

PMID- 29348438
TI  - Procalcitonin Guiding Antimicrobial Therapy Duration in Febrile Cancer Patients
      with Documented Infection or Neutropenia.
AB  - In this analysis, we identified febrile cancer patients with documented
      infections or neutropenia, whose procalcitonin levels are low at baseline or
      decrease on antibiotics. These patients had similar outcomes in terms of
      mortality and relapse of infection regardless of the duration of antimicrobial
      therapy (less or more than 7 days).

PMID- 29348439
TI  - Dual suppression of inner and outer mitochondrial membrane functions augments
      apoptotic responses to oncogenic MAPK inhibition.
AB  - Mitogen-activated protein kinase (MAPK) pathway inhibitors show promise in
      treating melanoma, but are unsuccessful in achieving long-term remission.
      Concordant with clinical data, BRAFV600E melanoma cells eliminate glycolysis upon
      inhibition of BRAFV600E or MEK with the targeted therapies Vemurafenib or
      Trametinib, respectively. Consequently, exposure to these therapies reprograms
      cellular metabolism to increase mitochondrial respiration and restrain cell death
      commitment. As the inner mitochondrial membrane (IMM) is sub-organellar site of
      oxidative phosphorylation (OXPHOS), and the outer mitochondrial membrane (OMM) is
      the major site of anti-apoptotic BCL-2 protein function, we hypothesized that
      suppressing these critical mitochondrial membrane functions would be a rational
      approach to maximize the pro-apoptotic effect of MAPK inhibition. Here, we
      demonstrate that disruption of OXPHOS with the mitochondria-specific protonophore
      BAM15 promotes the mitochondrial pathway of apoptosis only when oncogenic MAPK
      signaling is inhibited. Based on RNA-sequencing analyses of nevi and primary
      melanoma samples, increased pro-apoptotic BCL-2 family expression positively
      correlates with high-risk disease suggesting a highly active anti-apoptotic BCL-2
      protein repertoire likely contributes to worse outcome. Indeed, combined
      inhibition of the anti-apoptotic BCL-2 repertoire with BH3-mimetics, OXPHOS, and
      oncogenic MAPK signaling induces fulminant apoptosis and eliminates clonogenic
      survival. Altogether, these data suggest that dual suppression of IMM and OMM
      functions may unleash the normally inadequate pro-apoptotic effects of oncogenic
      MAPK inhibition to eradicate cancer cells, thus preventing the development of
      resistant disease, and ultimately, supporting long-term remission.

PMID- 29348437
TI  - First experimental proof of Proton Boron Capture Therapy (PBCT) to enhance
      protontherapy effectiveness.
AB  - Protontherapy is hadrontherapy's fastest-growing modality and a pillar in the
      battle against cancer. Hadrontherapy's superiority lies in its inverted depth
      dose profile, hence tumour-confined irradiation. Protons, however, lack distinct
      radiobiological advantages over photons or electrons. Higher LET (Linear Energy
      Transfer) 12C-ions can overcome cancer radioresistance: DNA lesion complexity
      increases with LET, resulting in efficient cell killing, i.e. higher Relative
      Biological Effectiveness (RBE). However, economic and radiobiological issues
      hamper 12C-ion clinical amenability. Thus, enhancing proton RBE is desirable. To
      this end, we exploited the p + 11B -> 3alpha reaction to generate high-LET alpha
      particles with a clinical proton beam. To maximize the reaction rate, we used
      sodium borocaptate (BSH) with natural boron content. Boron-Neutron Capture
      Therapy (BNCT) uses 10B-enriched BSH for neutron irradiation-triggered alpha
      particles. We recorded significantly increased cellular lethality and chromosome
      aberration complexity. A strategy combining protontherapy's ballistic precision
      with the higher RBE promised by BNCT and 12C-ion therapy is thus demonstrated.

PMID- 29348440
TI  - Neural predictors of cognitive improvement by multi-strategic memory training
      based on metamemory in older adults with subjective memory complaints.
AB  - Previous studies have indicated that memory training may help older people
      improve cognition. However, evidence regarding who will benefit from such memory
      trainings has not been fully discovered yet. Understanding the clinical and
      neural inter-individual differences for predicting cognitive improvement is
      important for maximizing the training efficacy of memory-training programs. The
      purpose of this study was to find the individual characteristics and brain
      morphological characteristics that predict cognitive improvement after a multi
      strategic memory training based on metamemory concept. Among a total of 49 older
      adults, 39 participated in the memory-training program and 10 did not. All of
      them underwent brain MRIs at the entry of the training and received the
      neuropsychological tests twice, before and after the training. Stepwise
      regression analysis showed that lower years of education predicted cognitive
      improvement in the training group. In MRI, thinner cortices of precuneus, cuneus
      and posterior cingulate gyrus and higher white matter anisotropy of the splenium
      of corpus callosum predicted cognitive improvement in the training group. Old
      age, lower education level and individual differences in cortical thickness and
      white matter microstructure of the episodic memory network may predict outcomes
      following multi-strategic training.

PMID- 29348434
TI  - Identification of genetic elements in metabolism by high-throughput mouse
      phenotyping.
AB  - Metabolic diseases are a worldwide problem but the underlying genetic factors and
      their relevance to metabolic disease remain incompletely understood. Genome-wide
      research is needed to characterize so-far unannotated mammalian metabolic genes.
      Here, we generate and analyze metabolic phenotypic data of 2016 knockout mouse
      strains under the aegis of the International Mouse Phenotyping Consortium (IMPC)
      and find 974 gene knockouts with strong metabolic phenotypes. 429 of those had no
      previous link to metabolism and 51 genes remain functionally completely
      unannotated. We compared human orthologues of these uncharacterized genes in five
      GWAS consortia and indeed 23 candidate genes are associated with metabolic
      disease. We further identify common regulatory elements in promoters of candidate
      genes. As each regulatory element is composed of several transcription factor
      binding sites, our data reveal an extensive metabolic phenotype-associated
      network of co-regulated genes. Our systematic mouse phenotype analysis thus paves
      the way for full functional annotation of the genome.

PMID- 29348441
TI  - SDF1 gradient associates with the distribution of c-Kit+ cardiac cells in the
      heart.
AB  - Identification of the adult cardiac stem cells (CSCs) has offered new therapeutic
      possibilities for treating ischemic myocardium. CSCs positive for the cell
      surface antigen c-Kit are known as the primary source for cardiac regeneration.
      Accumulating evidence shows that chemokines play important roles in stem cell
      homing. Here we investigated molecular targets to be utilized in modulating the
      mobility of endogenous CSCs. In a four week follow-up after experimental acute
      myocardial infarction (AMI) with ligation of the left anterior descending (LAD)
      coronary artery of Sprague-Dawley rats c-Kit+ CSCs redistributed in the heart.
      The number of c-Kit+ CSCs in the atrial c-Kit niche was diminished, whereas
      increased amount was observed in the left ventricle and apex. This was associated
      with increased expression of stromal cell-derived factor 1 alpha (SDF1alpha), and
      a significant positive correlation was found between c-Kit+ CSCs and SDF1alpha
      expression in the heart. Moreover, the migratory capacity of isolated c-Kit+ CSCs
      was induced by SDF1 treatment in vitro. We conclude that upregulation of
      SDF1alpha after AMI associates with increased expression of endogenous c-Kit+
      CSCs in the injury area, and show induced migration of c-Kit+ cells by SDF1.

PMID- 29348442
TI  - A neutral ceramidase, NlnCDase, is involved in the stress responses of brown
      planthopper, Nilaparvata lugens (Stal).
AB  - Ceramidases (CDases) are vital enzymes involved in the biosynthesis of
      sphingolipids, which are essential components of eukaryotic membranes. The
      function of these enzymes in insects, however, is poorly understood. We
      identified a neutral ceramidase (NlnCDase) from the brown planthopper,
      Nilaparvata lugens, one of the most destructive hemipteran pests of rice. The C12
      ceramide was the most preferred substrate for the NlnCDase enzyme. The activity
      of the NlnCDase enzyme was highest in the neutral-pH range (pH 6.0). It was
      inhibited by EGTA, Cs+ and Fe2+, while stimulated by EDTA and Ca2+. Moreover, the
      NlnCDase has higher transcript level and activity in adults than in eggs and
      nymphs, and in the reproductive organs (ovaries and spermaries) than in other
      tissues (i.e. heads, thorax, legs, midguts), which suggested that the NlnCDase
      might be elevated to mediate developmental process. In addition, transcripts and
      activity of the NlnCDase were up-regulated under abiotic stresses including
      starvation, abnormal temperature, and insecticides, and biotic stress of
      resistant rice varieties. Knocking down NlnCDase by RNA interference increased
      female survival under starvation and temperature stresses, suggesting that
      NlnCDase might be involved in the stress response in N. lugens.

PMID- 29348444
TI  - ToxicDocs (www.ToxicDocs.org): from history buried in stacks of paper to open,
      searchable archives online.
AB  - As a result of a legal mechanism called discovery, the authors accumulated
      millions of internal corporate and trade association documents related to the
      introduction of new products and chemicals into workplaces and commerce. What did
      these private entities discuss among themselves and with their experts? The
      plethora of documents, both a blessing and a curse, opened new sources and
      interesting questions about corporate and regulatory histories. But they also
      posed an almost insurmountable challenge to historians. Thus emerged ToxicDocs,
      possible only with a technological innovation known as "Big Data." That refers to
      the sheer volume of new digital data and to the computational power to analyze
      them. Users will be able to identify what firms knew (or did not know) about the
      dangers of toxic substances in their products-and when. The database opens many
      areas to inquiry including environmental studies, business history, government
      regulation, and public policy. ToxicDocs will remain a resource free and open to
      all, anywhere in the world.

PMID- 29348445
TI  - ToxicDocs: a new resource for assessing the impact of corporate practices on
      health.

PMID- 29348443
TI  - A general and flexible method for signal extraction from single-cell RNA-seq
      data.
AB  - Single-cell RNA-sequencing (scRNA-seq) is a powerful high-throughput technique
      that enables researchers to measure genome-wide transcription levels at the
      resolution of single cells. Because of the low amount of RNA present in a single
      cell, some genes may fail to be detected even though they are expressed; these
      genes are usually referred to as dropouts. Here, we present a general and
      flexible zero-inflated negative binomial model (ZINB-WaVE), which leads to low
      dimensional representations of the data that account for zero inflation
      (dropouts), over-dispersion, and the count nature of the data. We demonstrate,
      with simulated and real data, that the model and its associated estimation
      procedure are able to give a more stable and accurate low-dimensional
      representation of the data than principal component analysis (PCA) and zero
      inflated factor analysis (ZIFA), without the need for a preliminary normalization
      step.

PMID- 29348446
TI  - ToxicDocs (www.ToxicDocs.org) goes live: A giant step toward leveling the playing
      field for efforts to combat toxic exposures.

PMID- 29348447
TI  - Browsing a corporation's mind.

PMID- 29348449
TI  - ToxicDocs and the fight against biased public health science worldwide.

PMID- 29348448
TI  - Archival sources on asbestos and silicosis in Southern Africa and Australia.

PMID- 29348450
TI  - The value of not being lost in our digital world.

PMID- 29348451
TI  - ToxicDocs: using the US legal system to confront industries' systematic
      counterattacks against public health.

PMID- 29348452
TI  - Combination Therapy Strategy of Quorum Quenching Enzyme and Quorum Sensing
      Inhibitor in Suppressing Multiple Quorum Sensing Pathways of P. aeruginosa.
AB  - The threat of antibiotic resistant bacteria has called for alternative
      antimicrobial strategies that would mitigate the increase of classical resistance
      mechanism. Many bacteria employ quorum sensing (QS) to govern the production of
      virulence factors and formation of drug-resistant biofilms. Targeting the
      mechanism of QS has proven to be a functional alternative to conventional
      antibiotic control of infections. However, the presence of multiple QS systems in
      individual bacterial species poses a challenge to this approach. Quorum sensing
      inhibitors (QSI) and quorum quenching enzymes (QQE) have been both investigated
      for their QS interfering capabilities. Here, we first simulated the combination
      effect of QQE and QSI in blocking bacterial QS. The effect was next validated by
      experiments using AiiA as QQE and G1 as QSI on Pseudomonas aeruginosa LasR/I and
      RhlR/I QS circuits. Combination of QQE and QSI almost completely blocked the P.
      aeruginosa las and rhl QS systems. Our findings provide a potential chemical
      biology application strategy for bacterial QS disruption.

PMID- 29348453
TI  - Enhanced anastomotic healing by Daikenchuto (TJ-100) in rats.
AB  - Daikenchuto (DKT), a traditional Japanese medicine, is widely used to treat
      various gastrointestinal disorders. This study aimed to investigate whether DKT
      could promote the anastomotic healing in a rat model. Pedicled colonic segments
      were made in left colon by ligation of the feeding arteries, and then intestinal
      continuity was restored. Colonic blood flow was analyzed by using ICG
      fluorescence imaging: Fmax, Tmax, T1/2, and Slope were calculated. Anastomotic
      leakage (AL) was found in 6 of 19 rats (31.6%) in the control group, whereas in 1
      of 16 rats (6.2%) in the DKT group. The Fmax and Slope of DKT group were
      significantly higher than those of control group. DKT could promote the
      anastomotic healing, with the higher bursting pressure on postoperative day (POD)
      2 and 5, the larger granulation thickness on POD 5, and neoangiogenesis on POD 5.
      Histological examination showed DKT exhibited a decreased inflammatory cell
      infiltration, enhanced fibroblast infiltration, and enhanced collagen density on
      POD 5. In the DKT group, the levels of TGFbeta1 on POD 2 and VEGFalpha on POD5
      were significantly higher, whereas the level of TNFalpha on POD 2 was
      significantly lower. Therefore, DKT could be effective for the prevention of AL
      following colorectal surgery.

PMID- 29348454
TI  - Harnessing insulin- and leptin-induced oxidation of PTP1B for therapeutic
      development.
AB  - The protein tyrosine phosphatase PTP1B is a major regulator of glucose
      homeostasis and energy metabolism, and a validated target for therapeutic
      intervention in diabetes and obesity. Nevertheless, it is a challenging target
      for inhibitor development. Previously, we generated a recombinant antibody
      (scFv45) that recognizes selectively the oxidized, inactive conformation of
      PTP1B. Here, we provide a molecular basis for its interaction with reversibly
      oxidized PTP1B. Furthermore, we have identified a small molecule inhibitor that
      mimics the effects of scFv45. Our data provide proof-of-concept that
      stabilization of PTP1B in an inactive, oxidized conformation by small molecules
      can promote insulin and leptin signaling. This work illustrates a novel paradigm
      for inhibiting the signaling function of PTP1B that may be exploited for
      therapeutic intervention in diabetes and obesity.

PMID- 29348455
TI  - Programmed cell death can increase the efficacy of microbial bet -hedging.
AB  - Programmed cell death (PCD) occurs in both unicellular and multicellular
      organisms. While PCD plays a key role in the development and maintenance of
      multicellular organisms, explaining why single-celled organisms would evolve to
      actively commit suicide has been far more challenging. Here, we explore the
      potential for PCD to act as an accessory to microbial bet-hedging strategies that
      utilize stochastic phenotype switching. We consider organisms that face
      unpredictable and recurring disasters, in which fitness depends on effective
      phenotypic diversification. We show that when reproductive opportunities are
      limited by carrying capacity, PCD drives population turnover, providing increased
      opportunities for phenotypic diversification through stochastic phenotype
      switching. The main cost of PCD, providing resources for growth to a PCD(-)
      competitor, is ameliorated by genetic assortment in spatially structured
      populations. Using agent -based simulations, we explore how basic demographic
      factors, namely bottlenecks and local dispersal, can generate sufficient spatial
      structure to favor the evolution of high PCD rates.

PMID- 29348456
TI  - TWIST1 induces expression of discoidin domain receptor 2 to promote ovarian
      cancer metastasis.
AB  - The mesenchymal gene program has been shown to promote the metastatic progression
      of ovarian cancer; however, specific proteins induced by this program that lead
      to these metastatic behaviors have not been identified. Using patient derived
      tumor cells and established human ovarian tumor cell lines, we find that the
      Epithelial-to-Mesenchymal Transition inducing factor TWIST1 drives expression of
      discoidin domain receptor 2 (DDR2), a receptor tyrosine kinase (RTK) that
      recognizes fibrillar collagen as ligand. The expression and action of DDR2 was
      critical for mesothelial cell clearance, invasion and migration in ovarian tumor
      cells. It does so, in part, by upregulating expression and activity of matrix
      remodeling enzymes that lead to increased cleavage of fibronectin and spreading
      of tumor cells. Additionally, DDR2 stabilizes SNAIL1, allowing for sustained
      mesenchymal phenotype. In patient derived ovarian cancer specimens, DDR2
      expression correlated with enhanced invasiveness. DDR2 expression was associated
      with advanced stage ovarian tumors and metastases. In vivo studies demonstrated
      that the presence of DDR2 is critical for ovarian cancer metastasis. These
      findings indicate that the collagen receptor DDR2 is critical for multiple steps
      of ovarian cancer progression to metastasis, and thus, identifies DDR2 as a
      potential new target for the treatment of metastatic ovarian cancer.

PMID- 29348457
TI  - LTBP3 promotes early metastatic events during cancer cell dissemination.
AB  - Latent transforming growth factor beta (TGFbeta)-binding proteins (LTBPs) are
      important for the secretion, activation, and function of mature TGFbeta,
      especially so in cancer cell physiology. However, specific roles of the LTBPs
      remain understudied in the context of the primary tumor microenvironment. Herein,
      we investigated the role of LTBP3 in the distinct processes involved in cancer
      metastasis. By using three human tumor cell lines of different tissue origin
      (epidermoid HEp-3 and prostate PC-3 carcinomas and HT-1080 fibrosarcoma) and
      several metastasis models conducted in both mammalian and avian settings, we show
      that LTBP3 is involved in the early dissemination of primary cancer cells, namely
      in the intravasation step of the metastatic cascade. Knockdown of LTBP3 in all
      tested cell lines led to significant inhibition of tumor cell intravasation, but
      did not affect primary tumor growth. LTBP3 was dispensable in the late steps of
      carcinoma cell metastasis that follow tumor cell intravasation, including
      vascular arrest, extravasation, and tissue colonization. However, LTBP3 depletion
      diminished the angiogenesis-inducing potential of HEp-3 cells in vivo, which was
      restorable by exogenous delivery of LTBP3 protein. A similar compensatory
      approach rescued the dampened intravasation of LTBP3-deficient HEp-3 cells,
      suggesting that LTBP3 regulates the induction of the intravasation-supporting
      angiogenic vasculature within developing primary tumors. Using our recently
      developed microtumor model, we confirmed that LTBP3 loss resulted in the
      development of intratumoral vessels with an abnormal microarchitecture
      incompatible with efficient intravasation of HEp-3 carcinoma cells. Collectively,
      these findings demonstrate that LTBP3 represents a novel oncotarget that has
      distinctive functions in the regulation of angiogenesis-dependent tumor cell
      intravasation, a critical process during early cancer dissemination. Our
      experimental data are also consistent with the survival prognostic value of LTBP3
      expression in early-stage head and neck squamous cell carcinomas, further
      indicating a specific role for LTBP3 in cancer progression toward metastatic
      disease.

PMID- 29348458
TI  - Hic-5 regulates fibrillar adhesion formation to control tumor extracellular
      matrix remodeling through interaction with tensin1.
AB  - The linearization of the stromal extracellular matrix (ECM) by cancer-associated
      fibroblasts (CAFs) facilitates tumor cell growth and metastasis. However, the
      mechanism by which the ECM is remodeled is not fully understood. Hic-5
      (TGFbeta1i1), a focal adhesion scaffold protein, has previously been reported to
      be crucial for stromal ECM deposition and remodeling in vivo. Herein we show that
      CAFs lacking Hic-5 exhibit a significant reduction in the ability to form
      fibrillar adhesions, a specialized form of focal adhesion that promote
      fibronectin fibrillogenesis. Hic-5 was found to promote fibrillar adhesion
      formation through a newly characterized interaction with tensin1. Furthermore,
      Src-dependent phosphorylation of Hic-5 facilitated the interaction with tensin1
      to prevent beta1 integrin internalization and trafficking to the lysosome. The
      interaction between Hic-5 and tensin1 was mechanosensitive, promoting fibrillar
      adhesion formation and fibronectin fibrillogenesis in a rigidity-dependent
      fashion. Importantly, this Src-dependent mechanism was conserved in three
      dimensional (3D) ECM environments. Immunohistochemistry of tensin1 showed
      enrichment in CAFs in vivo, which was abrogated upon deletion of Hic-5.
      Interestingly, elevated Hic-5 expression correlates with reduced distant
      metastasis-free survival in patients with basal-like, HER2+ and grade 3 tumors.
      Thus, we have identified Hic-5 as a crucial regulator of ECM remodeling in CAFs
      by promoting fibrillar adhesion formation through a novel interaction with
      tensin1.

PMID- 29348459
TI  - Distinct dependencies on receptor tyrosine kinases in the regulation of MAPK
      signaling between BRAF V600E and non-V600E mutant lung cancers.
AB  - BRAF is one of the most frequently mutated genes across a number of different
      cancers, with the best-characterized mutation being V600E. Despite the successes
      of treating BRAF mutant V600E lung cancer with BRAF pathway inhibitors, treatment
      strategies targeting tumors with non-V600E mutations are yet to be established.
      We studied cellular signaling differences between lung cancers with different
      BRAF mutations and determined their sensitivities to BRAF pathway inhibitors.
      Here, we observed that MEK inhibition induced feedback activation of the receptor
      tyrosine kinase (RTK) EGFR, and in some cases the RTK FGFR, resulting in
      transient suppression of ERK phosphorylation in BRAF non-V600E, but not BRAF
      V600E, mutant cells. Furthermore, we found that both EGFR and FGFR activated the
      MEK/ERK pathway, despite the presence of BRAF non-V600E mutations with elevated
      kinase activity. Moreover, in BRAF non-V600E mutants with impaired kinase
      activities, EGFR had even greater control over the MEK/ERK pathway, essentially
      contributing completely to the tonic mitogen-activated protein kinase (MAPK)
      signal. Accordingly, the combination of MEK inhibitor with EGFR inhibitor was
      effective at shrinking tumors in mouse model of BRAF non-V600E mutant lung
      cancer. Furthermore, the results were recapitulated with a clinically relevant
      dual inhibitor of EGFR and RAF, BGB-283. Overall, although BRAF V600E mutant
      cells are sensitive to BRAF inhibition, non-V600E mutant cancer cells are reliant
      on RTKs for their MAPK activation and inhibiting both MEK and RTKs are necessary
      in these cancers. Our findings provide evidence of critical survival signals in
      BRAF non-V600E mutant cancers, which could pave the way for effective treatment
      of these cancers.

PMID- 29348460
TI  - FYN promotes mesenchymal phenotypes of basal type breast cancer cells through
      STAT5/NOTCH2 signaling node.
AB  - Basal type breast cancer is the most aggressive and has mesenchymal features with
      a high metastatic ability. However, the signaling node that determines the basal
      type features in breast cancer remains obscure. Here, we report that FYN among
      SRC family kinases is required for the maintenance of basal type breast cancer
      subtype. Importantly, FYN enhanced NOTCH2 activation in basal type breast cancer
      cells through STAT5-mediated upregulation of Jagged-1 and DLL4 NOTCH ligands,
      thereby contributed to mesenchymal phenotypes. In addition, we found that high
      levels of FYN persist in basal type breast cancer cells by a positive feedback
      loop between FYN and STAT5. FYN interacted directly with STAT5 and increased p
      STAT5 that further acts as a transcription factor for FYN. Taken together, our
      findings demonstrate a pivotal role of FYN and its downstream effectors in
      maintaining the basal type features in breast cancer.

PMID- 29348461
TI  - Loss of Cdk5 in breast cancer cells promotes ROS-mediated cell death through
      dysregulation of the mitochondrial permeability transition pore.
AB  - Cdk5, which plays a role in the development and progression of many human
      cancers, localizes in the mitochondria, a key determinant of apoptotic cell
      death. Cdk5 is upregulated in breast cancer cells but it was shown that Cdk5 loss
      increases chemotherapy-induced apoptosis. However, the molecular mechanism by
      which Cdk5 loss promotes cell death remains unclear. Here, we investigate the
      possibility that Cdk5 loss activates the intrinsic apoptotic pathway in breast
      cancer cells. We demonstrate that Cdk5-deficient breast cancer cells exhibit
      increased mitochondrial depolarization, mitochondrial ROS levels, and
      mitochondrial fragmentation that is associated with an increase in both
      intracellular Ca2+ level and calcineurin activity, and DRP1 S637
      dephosphorylation. These events accompany increased apoptosis, indicating that
      Cdk5 loss promotes mitochondria-mediated apoptosis. To define this apoptotic
      pathway, we utilized various inhibitors of mitochondrial function. Apoptosis is
      completely prevented by mPTP inhibition, almost fully inhibited by blocking ROS
      and unaffected by inhibition of mitochondrial fission, suggesting that apoptosis
      in breast cancer cells due to Cdk5 loss occurs via a novel mPTP-dependent
      mechanism that acts primarily through ROS increase.

PMID- 29348462
TI  - Piperlongumine and p53-reactivator APR-246 selectively induce cell death in HNSCC
      by targeting GSTP1.
AB  - TP53 mutations frequently occur in head and neck squamous cell carcinoma (HNSCC)
      patients without human papillomavirus infection. The recurrence rate for these
      patients is distinctly high. It has been actively explored to identify agents
      that target TP53 mutations and restore wild-type (WT) TP53 activities in HNSCC.
      PRIMA-1 (p53-reactivation and induction of massive apoptosis-1) and its
      methylated analogue PRIMA-1Met (also called APR-246) were found to be able to
      reestablish the DNA-binding activity of p53 mutants and reinstate the functions
      of WT p53. Herein we report that piperlongumine (PL), an alkaloid isolated from
      Piper longum L., synergizes with APR-246 to selectively induce apoptosis and
      autophagic cell death in HNSCC cells, whereas primary and immortalized mouse
      embryonic fibroblasts and spontaneously immortalized non-tumorigenic human skin
      keratinocytes (HaCat) are spared from the damage by the co-treatment.
      Interestingly, PL-sensitized HNSCC cells to APR-246 are TP53 mutation
      independent. Instead, we demonstrated that glutathione S-transferase pi 1
      (GSTP1), a GST family member that catalyzes the conjugation of GSH with
      electrophilic compounds to fulfill its detoxification function, is highly
      expressed in HNSCC tissues. Administration of PL and APR-246 significantly
      suppresses GSTP1 activity, resulting in the accumulation of ROS, depletion of
      GSH, elevation of GSSG, and DNA damage. Ectopic expression of GSTP1 or pre
      treatment with antioxidant N-acetyl-L-cysteine (NAC) abrogates the ROS elevation
      and decreases DNA damage, apoptosis, and autophagic cell death prompted by PL/APR
      246. In addition, administration of PL and APR-246 impedes UMSCC10A xenograft
      tumor growth in SCID mice. Taken together, our data suggest that HNSCC cells are
      selectively sensitive to the combination of PL and APR-246 due to a remarkably
      synergistic effect of the co-treatment in the induction of ROS by suppression of
      GSTP1.

PMID- 29348463
TI  - The bone microstructure of polar "hypsilophodontid" dinosaurs from Victoria,
      Australia.
AB  - High-latitude (i.e., "polar") Mesozoic fauna endured months of twilight and
      relatively low mean annual temperatures. Yet non-avian dinosaurs flourished in
      this taxing environment. Fossils of basal ornithopod dinosaurs
      ("hypsilophodontids") are common in the Early Cretaceous high-latitude sediments
      of Victoria, Australia, and four taxa have been described; although their
      ontogenetic histories are largely unexplored. In the present study, eighteen
      tibiae and femora were utilized in the first multi-specimen ontogenetic
      histological analysis of Australian polar hypsilophodontids. The sample consists
      of eleven individuals from the Flat Rocks locality (Late Valanginian or
      Barremian), and five from the Dinosaur Cove locality (Albian). In both groups,
      growth was most rapid during the first three years, and skeletal maturity
      occurred between five and seven years. There is a weak asymptotic trend in a plot
      of growth mark count versus femur length, with considerable individual variation.
      Histology suggests two genera are present within the Dinosaur Cove sample, but
      bone microstructure alone could not distinguish genera within the Flat Rocks
      sample, or across the two geologically separate (~ 26 Ma) localities. Additional
      histologic sampling, combined with morphological analyses, may facilitate further
      differentiation between ontogenetic, individual, and species variation.

PMID- 29348464
TI  - 150,000-year palaeoclimate record from northern Ethiopia supports early, multiple
      dispersals of modern humans from Africa.
AB  - Climatic change is widely acknowledged to have played a role in the dispersal of
      modern humans out of Africa, but the timing is contentious. Genetic evidence
      links dispersal to climatic change ~60,000 years ago, despite increasing evidence
      for earlier modern human presence in Asia. We report a deep seismic and near
      continuous core record of the last 150,000 years from Lake Tana, Ethiopia, close
      to early modern human fossil sites and to postulated dispersal routes. The record
      shows varied climate towards the end of the penultimate glacial, followed by an
      abrupt change to relatively stable moist climate during the last interglacial.
      These conditions could have favoured selection for behavioural versatility,
      population growth and range expansion, supporting models of early, multiple
      dispersals of modern humans from Africa.

PMID- 29348465
TI  - Publisher Correction: EFHD2 promotes epithelial-to-mesenchymal transition and
      correlates with postsurgical recurrence of stage I lung adenocarcinoma.
AB  - A correction to this article has been published and is linked from the HTML
      version of this paper. The error has been fixed in the paper.

PMID- 29348466
TI  - Gender specific association of parathyroid hormone and vitamin D with metabolic
      syndrome in population with preserved renal function.
AB  - The association of parathyroid hormone (PTH) and vitamin D with Metabolic
      syndrome (MetS) was evaluated using representative data from the Korean
      population. Data from 7004 subjects aged 50 or older with preserved renal
      function (excluding chronic kidney disease stage 3b to 5) who were included in
      the Korean National Health and Nutrition Examination Survey between 2008 and 2010
      were analysed. Higher PTH levels (pg/ml) were observed in subjects with MetS than
      in those without MetS among both genders (60.1 (58.6-61.6) vs. 62.4 (60.7-64.2)
      in males p = 0.018, 60.7 (59.4-62.1) vs. 63.9 (62.4-65.6) in females, p < 0.001).
      For females, PTH levels were significantly higher in subjects with MetS than in
      those without MetS after adjustment for possible covariates. Lower 25(OH)D levels
      were significantly associated with MetS only in male subjects (p = 0.004). As the
      number of MetS components increased, a significant rise in PTH levels (p for
      trend 0.005 in males and 0.024 in females) and a decrease in 25(OH)D levels (p
      for trend < 0.001 in males and 0.053 in females) were observed. In conclusion,
      among subjects with preserved renal function, PTH levels were possibly associated
      with MetS in females, whereas vitamin D levels exhibited a possible link to MetS
      in males.

PMID- 29348467
TI  - Efficacy of MEK inhibition in a K-Ras-driven cholangiocarcinoma preclinical
      model.
AB  - Intrahepatic cholangiocarcinoma (iCCA) is a deadly malignancy with limited
      treatment options. Gain-of-function mutations in K-Ras is a very frequent
      alteration, occurring in ~15 to 25% of human iCCA patients. Here, we established
      a new iCCA model by expressing activated forms of Notch1 (NICD) and K-Ras (K
      RasV12D) in the mouse liver (K-Ras/NICD mice). Furthermore, we investigated the
      therapeutic potential of MEK inhibitors in vitro and in vivo using human CCA cell
      lines and K-Ras/NICD mice, respectively. Treatment with U0126, PD901, and
      Selumetinib MEK inhibitors triggered growth restraint in all CCA cell lines
      tested, with the most pronounced growth suppressive effects being observed in K
      Ras mutant cells. Growth inhibition was due to reduction in proliferation and
      massive apoptosis. Furthermore, treatment of K-Ras/NICD tumor-bearing mice with
      PD901 resulted in stable disease. At the molecular level, PD901 efficiently
      inhibited ERK activation in K-Ras/NICD tumor cells, mainly leading to increased
      apoptosis. Altogether, our study demonstrates that K-Ras/NICD mice represent a
      novel and useful preclinical model to study K-Ras-driven iCCA development and the
      effectiveness of MEK inhibitors in counteracting this process. Our data support
      the usefulness of MEK inhibitors for the treatment of human iCCA.

PMID- 29348468
TI  - The potential impact of invasive woody oil plants on protected areas in China
      under future climate conditions.
AB  - Biodiesel produced from woody oil plants is considered a green substitute for
      fossil fuels. However, a potential negative impact of growing woody oil plants on
      a large scale is the introduction of highly invasive species into susceptible
      regions. In this study, we examined the potential invasion risk of woody oil
      plants in China's protected areas under future climate conditions. We simulated
      the current and future potential distributions of three invasive woody oil
      plants, Jatropha curcas, Ricinus communis, and Aleurites moluccana, under two
      climate change scenarios (RCP2.6 and RCP8.5) up to 2050 using species
      distribution models. Protected areas in China that will become susceptible to
      these species were then identified using a spatial overlay analysis. Our results
      showed that by 2050, 26 and 41 protected areas would be threatened by these
      invasive woody oil plants under scenarios RCP2.6 and RCP8.5, respectively. A
      total of 10 unique forest ecosystems and 17 rare plant species could be
      potentially affected. We recommend that the invasive potential of woody oil
      plants be fully accounted for when developing forest-based biodiesel, especially
      around protected areas.

PMID- 29348469
TI  - Treprostinil inhibits proliferation and extracellular matrix deposition by
      fibroblasts through cAMP activation.
AB  - Idiopathic pulmonary fibrosis (IPF) is characterized by peripheral lung fibrosis
      and increased interstitial extracellular matrix (ECM) deposition. In IPF, tumor
      growth factor (TGF)-beta1 which is the major stimulus of ECM deposition, and
      platelet derived growth factor (PDGF)-BB is a potent stimulus of fibrosis. Thus,
      the effect of Treprostinil on TGF-beta1 and PDGF-induced fibroblast proliferation
      and ECM deposition was investigated. Human peripheral lung fibroblasts of seven
      IPF patients and five lung donors were stimulated by PDGF, or TGF-beta1, or the
      combination. Cells were pre-incubated (30 min) with either Treprostinil,
      forskolin, di-deoxyadenosine (DDA), or vehicle. Treprostinil time dependently
      activated cAMP thereby preventing PDGF-BB induced proliferation and TGF-beta1
      secretion. Cell counts indicated proliferation; alpha-smooth muscle actin (alpha
      SMA) indicted differentiation, and collagen type-1 or fibronectin deposition
      remodeling. Myo-fibroblast indicating alpha-SMA expression was significantly
      reduced and its formation was altered by Treprostinil. Collagen type-I and
      fibronectin deposition were also reduced by Treprostinil. The effect of
      Treprostinil on collagen type-I deposition was cAMP sensitive as it was
      counteracted by DDA, while the effect on fibronectin was not cAMP mediated.
      Treprostinil antagonized the pro-fibrotic effects of both PDGF-BB and TGF-beta1
      in primary human lung fibroblasts. The data presented propose a therapeutic
      relevant anti-fibrotic effect of Treprostinil in IPF.

PMID- 29348470
TI  - Fibroblast growth factor 21 increases insulin sensitivity through specific
      expansion of subcutaneous fat.
AB  - Although the pharmacological effects of fibroblast growth factor 21 (FGF21) are
      well-documented, uncertainty about its role in regulating excessive energy intake
      remains. Here, we show that FGF21 improves systemic insulin sensitivity by
      promoting the healthy expansion of subcutaneous adipose tissue (SAT). Serum FGF21
      levels positively correlate with the SAT area in insulin-sensitive obese
      individuals. FGF21 knockout mice (FGF21KO) show less SAT mass and are more
      insulin-resistant when fed a high-fat diet. Replenishment of recombinant FGF21 to
      a level equivalent to that in obesity restores SAT mass and reverses insulin
      resistance in FGF21KO, but not in adipose-specific betaklotho knockout mice.
      Moreover, transplantation of SAT from wild-type to FGF21KO mice improves insulin
      sensitivity in the recipients. Mechanistically, circulating FGF21 upregulates
      adiponectin in SAT, accompanied by an increase of M2 macrophage polarization. We
      propose that elevated levels of endogenous FGF21 in obesity serve as a defense
      mechanism to protect against systemic insulin resistance.

PMID- 29348471
TI  - Three Dimensional Evaluation of Posterior Pole and Optic Nerve Head in Tilted
      Disc.
AB  - For over a century, tilted disc syndrome (TDS) has been defined vaguely. The lack
      of consensus of the terminology arises from the lack of understanding of the
      pathogenesis of this condition. Also, myopic discs with temporal crescents or
      peripapillary atrophy (PPA) are histologically indistinguishable from TDS.
      Therefore, we examined the morphological background of the extreme ONH
      appearances such as the myopic tilted disc and the TDS by analyzing the posterior
      segment of the eye from a three-dimensional (3D) perspective. 107 eyes of 107
      subjects were classified into 3 groups with respect to the optic disc torsion
      degrees: (1) mild torsion (0-30 degrees; 35 eyes) and (2) moderate torsion (30-60
      degrees; 35 eyes) and (3) severe torsion (60-90 degrees; 37 eyes). SSOCT images
      were analyzed in coronal view, which supplements anterior-posterior depth (z axis
      in Cartesian coordinates). The amount of optic disc torsion was significantly
      correlated with Disc-DPE angle and Fovea-Disc depth (r = 0.548, P < 0.001 and r =
      0.544, P < 0.001). In conclusion, we describe specific types of posterior sclera
      configuration that corresponds to the increasing degree of optic disc torsion,
      even in the extreme ONH appearances such as the myopic tilted disc and the TDS.
      These findings suggest that the optic disc appearance is determined by the
      configuration of the posterior sclera.

PMID- 29348473
TI  - Gene therapy: Autoimmune diabetes reversed in mice.

PMID- 29348474
TI  - Adrenal disease: Imitating the cortisol profile improves the immune system.

PMID- 29348472
TI  - Viral highway to nucleus exposed by image correlation analyses.
AB  - Parvoviral genome translocation from the plasma membrane into the nucleus is a
      coordinated multistep process mediated by capsid proteins. We used fast confocal
      microscopy line scan imaging combined with image correlation methods including
      auto-, pair- and cross-correlation, and number and brightness analysis, to study
      the parvovirus entry pathway at the single-particle level in living cells. Our
      results show that the endosome-associated movement of virus particles fluctuates
      from fast to slow. Fast transit of single cytoplasmic capsids to the nuclear
      envelope is followed by slow movement of capsids and fast diffusion of capsid
      fragments in the nucleoplasm. The unique combination of image analyses allowed us
      to follow the fate of intracellular single virus particles and their interactions
      with importin beta revealing previously unknown dynamics of the entry pathway.

PMID- 29348475
TI  - Osteoporosis: Community-based screening reduces hip fracture risk.

PMID- 29348477
TI  - Thyroid cancer: Balancing benefit and risk in TSH management of DTC.

PMID- 29348478
TI  - Metabolism: Leptin's role in starvation.

PMID- 29348479
TI  - Prime-boost vaccination with recombinant protein and adenovirus-vector expressing
      Plasmodium vivax circumsporozoite protein (CSP) partially protects mice against
      Pb/Pv sporozoite challenge.
AB  - Vaccine development against Plasmodium vivax malaria lags behind that for
      Plasmodium falciparum. To narrow this gap, we administered recombinant antigens
      based on P. vivax circumsporozoite protein (CSP) to mice. We expressed in Pichia
      pastoris two chimeric proteins by merging the three central repeat regions of
      different CSP alleles (VK210, VK247, and P. vivax-like). The first construct
      (yPvCSP-AllFL) contained the fused repeat regions flanked by N- and C-terminal
      regions. The second construct (yPvCSP-AllCT) contained the fused repeat regions
      and the C-terminal domain, plus RI region. Mice were vaccinated with three doses
      of yPvCSP in adjuvants Poly (I:C) or Montanide ISA720. We also used replication
      defective adenovirus vectors expressing CSP of human serotype 5 (AdHu5) and
      chimpanzee serotype 68 (AdC68) for priming mice which were subsequently boosted
      twice with yPvCSP proteins in Poly (I:C) adjuvant. Regardless of the regime used,
      immunized mice generated high IgG titres specific to all CSP alleles. After
      challenge with P. berghei ANKA transgenic parasites expressing Pb/PvVK210 or
      Pb/PvVK247 sporozoites, significant time delays for parasitemia were observed in
      all vaccinated mice. These vaccine formulations should be clinically tried for
      their potential as protective universal vaccine against P. vivax malaria.

PMID- 29348480
TI  - Association between plasma concentrations of branched-chain amino acids and
      adipokines in Japanese adults without diabetes.
AB  - Previous studies have consistently reported an association between circulating
      levels of branched-chain amino acids (BCAAs) or adipokines and insulin
      resistance; however, the association between BCAA and adipokine levels remains to
      be clarified. In this cross-sectional study involving 678 participants (435 men)
      without diabetes, plasma BCAA (valine, leucine, and isoleucine), adipokine (total
      and high molecular weight [HMW] adiponectin, leptin, and tumor necrosis factor
      alpha [TNF-alpha]) concentrations, and an updated homeostasis model assessment of
      insulin resistance (HOMA2-IR) were measured. The association between the
      concentrations of total BCAAs and adipokines was adjusted for confounding
      factors, including body mass index. For the lowest and highest BCAA quartiles,
      the adjusted geometric mean levels of HMW adiponectin were, respectively, 1.51
      and 0.91 MUg/mL, in men (P for trend < 0.0001); 3.61 and 2.29 MUg/mL, in women (P
      = 0.0005). The corresponding geometric mean levels for leptin were 1681 and 2620
      pg/mL, in men (P = 0.003), and 4270 and 6510 pg/mL, in women (P = 0.003). Those
      for HOMA2-IR were 0.89 and 1.11, in men (P < 0.0001), and 0.79 and 0.96, in women
      (P < 0.0001); no significant association was found with TNF-alpha. These results
      suggest significant associations between BCAA concentrations and those for
      adiponectin, leptin and HOMA2-IR in individuals without diabetes.

PMID- 29348481
TI  - Effects of graphene intercalation on dielectric reliability of HfO2 and
      modulation of effective work function for Ni/Gr/c-HfO2 interfaces: first
      principles study.
AB  - We have investigated the effects of graphene intercalation on dielectric
      reliability of HfO2 for Ni/Gr/HfO2 interfaces, and the effects of graphene
      intercalation and interfacial atom vacancy on the effective work function (EWF)
      of Ni/Gr/HfO2 interfaces using first-principle calculation based on density
      functional theory. The calculated results indicate that graphene intercalation
      can improve dielectric reliability of HfO2 dielectric even for the interfaces
      having interfacial oxygen vacancy or a small amount carbon vacancy. Moreover, the
      calculated results indicate that, inserting graphene into Ni/HfO2 interface
      induces the EWF's to decline, and controlling interfacial oxygen or carbon
      vacancy can effectively tune the EWF of Ni/Gr/HfO2 interface. Our work strongly
      suggests that the use of graphene synthesized into Ni/HfO2 interface is a very
      effective way to improve the interface quality, and controlling interfacial
      oxygen or carbon vacancy is also an attractive and promising way for modulating
      the EWF of Ni/Gr/HfO2 interfaces.

PMID- 29348476
TI  - Animal models of obesity and diabetes mellitus.
AB  - More than one-third of the worldwide population is overweight or obese and
      therefore at risk of developing type 2 diabetes mellitus. In order to mitigate
      this pandemic, safer and more potent therapeutics are urgently required. This
      necessitates the continued use of animal models to discover, validate and
      optimize novel therapeutics for their safe use in humans. In order to improve the
      transition from bench to bedside, researchers must not only carefully select the
      appropriate model but also draw the right conclusions. In this Review, we
      consolidate the key information on the currently available animal models of
      obesity and diabetes and highlight the advantages, limitations and important
      caveats of each of these models.

PMID- 29348482
TI  - EGFR activation triggers cellular hypertrophy and lysosomal disease in NAGLU
      depleted cardiomyoblasts, mimicking the hallmarks of mucopolysaccharidosis IIIB.
AB  - Mucopolysaccharidosis (MPS) IIIB is an inherited lysosomal storage disease caused
      by the deficiency of the enzyme alpha-N-acetylglucosaminidase (NAGLU) required
      for heparan sulfate (HS) degradation. The defective lysosomal clearance of
      undigested HS results in dysfunction of multiple tissues and organs. We recently
      demonstrated that the murine model of MPS IIIB develops cardiac disease, valvular
      abnormalities, and ultimately heart failure. To address the molecular mechanisms
      governing cardiac dysfunctions in MPS IIIB, we generated a model of the disease
      by silencing NAGLU gene expression in H9C2 rat cardiomyoblasts. NAGLU-depleted
      H9C2 exhibited accumulation of abnormal lysosomes and a hypertrophic phenotype.
      Furthermore, we found the specific activation of the epidermal growth factor
      receptor (EGFR), and increased phosphorylation levels of extracellular signal
      regulated kinases (ERKs) in NAGLU-depleted H9C2. The inhibition of either EGFR or
      ERKs, using the selective inhibitors AG1478 and PD98059, resulted in the
      reduction of both lysosomal aberration and hypertrophy in NAGLU-depleted H9C2. We
      also found increased phosphorylation of c-Src and a reduction of the hypertrophic
      response in NAGLU-depleted H9C2 transfected with a dominant-negative c-Src.
      However, c-Src phosphorylation remained unaffected by AG1478 treatment, posing c
      Src upstream EGFR activation. Finally, heparin-binding EGF-like growth factor (HB
      EGF) protein was found overexpressed in our MPS IIIB cellular model, and its
      silencing reduced the hypertrophic response. These results indicate that both c
      Src and HB-EGF contribute to the hypertrophic phenotype of NAGLU-depleted
      cardiomyoblasts by synergistically activating EGFR and subsequent signaling, thus
      suggesting that EGFR pathway inhibition could represent an effective therapeutic
      approach for MPS IIIB cardiac disease.

PMID- 29348483
TI  - Cell Type-Specific Survey of Epigenetic Modifications by Tandem Chromatin
      Immunoprecipitation Sequencing.
AB  - The nervous system of higher eukaryotes is composed of numerous types of neurons
      and glia that together orchestrate complex neuronal responses. However, this
      complex pool of cells typically poses analytical challenges in investigating gene
      expression profiles and their epigenetic basis for specific cell types. Here, we
      developed a novel method that enables cell type-specific analyses of epigenetic
      modifications using tandem chromatin immunoprecipitation sequencing (tChIP-Seq).
      FLAG-tagged histone H2B, a constitutive chromatin component, was first expressed
      in Camk2a-positive pyramidal cortical neurons and used to purify chromatin in a
      cell type-specific manner. Subsequent chromatin immunoprecipitation using
      antibodies against H3K4me3-a chromatin modification mainly associated with active
      promoters-allowed us to survey the histone modifications in Camk2a-positive
      neurons. Indeed, tChIP-Seq identified hundreds of H3K4me3 modifications in
      promoter regions located upstream of genes associated with neuronal functions and
      genes with unknown functions in cortical neurons. tChIP-Seq provides a versatile
      approach to investigating the epigenetic modifications of particular cell types
      in vivo.

PMID- 29348484
TI  - Activation of Ca2+-sensing receptor as a protective pathway to reduce Cadmium
      induced cytotoxicity in renal proximal tubular cells.
AB  - Cadmium (Cd), as an extremely toxic metal could accumulate in kidney and induce
      renal injury. Previous studies have proved that Cd impact on renal cell
      proliferation, autophagy and apoptosis, but the detoxification drugs and the
      functional mechanism are still in study. In this study, we used mouse renal
      tubular epithelial cells (mRTECs) to clarify Cd-induced toxicity and signaling
      pathways. Moreover, we proposed to elucidate the prevent effect of activation of
      Ca2+ sensing receptor (CaSR) by Calcimimetic (R-467) on Cd-induced cytotoxicity
      and underlying mechanisms. Cd induced intracellular Ca2+ elevation through
      phospholipase C-inositol 1, 4, 5-trisphosphate (PLC) followed stimulating p38
      mitogen-activated protein kinases (MAPK) activation and suppressing extracellular
      signal-regulated kinase (ERK) activation, which leaded to increase apoptotic cell
      death and inhibit cell proliferation. Cd induced p38 activation also contribute
      to autophagic flux inhibition that aggravated Cd induced apoptosis. R-467
      reinstated Cd-induced elevation of intracellular Ca2+ and apoptosis, and it also
      increased cell proliferation and restored autophagic flux by switching p38 to ERK
      pathway. The identification of the activation of CaSR-mediated protective pathway
      in renal cells sheds light on a possible cellular protective mechanism against Cd
      induced kidney injury.

PMID- 29348486
TI  - Phase I dose-escalation study of copanlisib in combination with gemcitabine or
      cisplatin plus gemcitabine in patients with advanced cancer.
AB  - BACKGROUND: Copanlisib is a pan-class I phosphatidylinositol 3-kinase (PI3K)
      inhibitor with predominant PI3K-alpha/delta activity that has demonstrated
      clinical activity and manageable safety when administered as monotherapy in a
      phase II study. Combination therapy may overcome compensatory signalling that
      could occur with PI3K pathway inhibition, resulting in enhanced inhibitory
      activity, and preclinical studies of copanlisib with gemcitabine have
      demonstrated potent anti-tumour activity in vivo. METHODS: A phase I, open-label,
      dose-escalation study to evaluate the safety, tolerability and recommended phase
      II dose (RP2D) of copanlisib with gemcitabine or with cisplatin plus gemcitabine
      (CisGem) in patients with advanced malignancies, including an expansion cohort in
      patients with biliary tract cancer (BTC) at the RP2D of copanlisib plus CisGem.
      Copanlisib and gemcitabine were administered on days 1, 8 and 15 of a 28-day
      cycle; maximum tolerated dose (MTD) and RP2D of copanlisib were determined.
      Copanlisib plus CisGem was administered on days 1 and 8 of a 21-day cycle;
      pharmacokinetics and biomarkers were assessed. RESULTS: Fifty patients received
      treatment as follows: dose-escalation cohorts, n=16; copanlisib plus CisGem
      cohort, n=14; and BTC expansion cohort, n=20. Copanlisib 0.8 mg kg-1 plus
      gemcitabine was the MTD and RP2D for both combinations. Common treatment-emergent
      adverse events included nausea (86%), hyperglycaemia (80%) and decreased platelet
      count (80%). Copanlisib exposure displayed a dose-proportional increase. No
      differences were observed upon co-administration of CisGem. Response rates were
      as follows: copanlisib plus gemcitabine, 6.3% (one partial response in a patient
      with peritoneal carcinoma); copanlisib plus CisGem, 12% (one complete response
      and three partial responses all in patients with BTC (response rate 17.4% in
      patients with BTC)). Mutations were detected in PIK3CA (1 out of 43), KRAS (10
      out of 43) and BRAF (2 out of 22), with phosphate and tensin homologue protein
      loss in 41% (12 out of 29). CONCLUSIONS: Copanlisib plus CisGem demonstrated a
      manageable safety profile, favourable pharmacokinetics, and potentially promising
      clinical response.

PMID- 29348485
TI  - Motor signatures of emotional reactivity in frontotemporal dementia.
AB  - Automatic motor mimicry is essential to the normal processing of perceived
      emotion, and disrupted automatic imitation might underpin socio-emotional
      deficits in neurodegenerative diseases, particularly the frontotemporal
      dementias. However, the pathophysiology of emotional reactivity in these diseases
      has not been elucidated. We studied facial electromyographic responses during
      emotion identification on viewing videos of dynamic facial expressions in 37
      patients representing canonical frontotemporal dementia syndromes versus 21
      healthy older individuals. Neuroanatomical associations of emotional expression
      identification accuracy and facial muscle reactivity were assessed using voxel
      based morphometry. Controls showed characteristic profiles of automatic
      imitation, and this response predicted correct emotion identification. Automatic
      imitation was reduced in the behavioural and right temporal variant groups, while
      the normal coupling between imitation and correct identification was lost in the
      right temporal and semantic variant groups. Grey matter correlates of emotion
      identification and imitation were delineated within a distributed network
      including primary visual and motor, prefrontal, insular, anterior temporal and
      temporo-occipital junctional areas, with common involvement of supplementary
      motor cortex across syndromes. Impaired emotional mimesis may be a core mechanism
      of disordered emotional signal understanding and reactivity in frontotemporal
      dementia, with implications for the development of novel physiological biomarkers
      of socio-emotional dysfunction in these diseases.

PMID- 29348487
TI  - H1/pHGFK1 nanoparticles exert anti-tumoural and radiosensitising effects by
      inhibition of MET in glioblastoma.
AB  - BACKGROUND: The therapeutic resistance to ionising radiation (IR) and anti
      angiogenesis mainly impair the prognosis of patients with glioblastoma. The
      primary and secondary MET aberrant activation is one crucial factor for these
      resistances. The kringle 1 domain of hepatocyte growth factor (HGFK1), an
      angiogenic inhibitor, contains a high-affinity binding domain of MET; however,
      its effects on glioblastoma remain elusive. METHODS: We formed the nanoparticles
      consisting of a folate receptor-targeted nanoparticle-mediated HGFK1 gene
      (H1/pHGFK1) and studied its anti-tumoural and radiosensitive activities in both
      subcutaneous and orthotopic human glioma cell-xenografted mouse models. We then
      elucidated its molecular mechanisms in human glioblastoma cell lines in vitro.
      RESULTS: We demonstrated for the first time that peritumoural injection of
      H1/pHGFK1 nanoparticles significantly inhibited tumour growth and prolonged
      survival in tumour-bearing mice, as well as enhanced the anti-tumoural efficacies
      of IR in vivo by reducing Ki-67 expression, enhancing TUNEL staining-indicated
      apoptotic indexes, reducing microvascular intensity and reversing IR-induced MET
      overexpression in tumour tissues. Furthermore, we showed that HGFK1 suppressed
      the proliferation and induced cell apoptosis and enhanced sensitivity to IR in
      glioblastoma cell lines, mainly by suppressing the activities of MET receptor,
      down-regulating ATM-Chk2 axis but up-regulating Chk1. CONCLUSIONS: H1/pHGFK1
      exerts anti-tumoural and radiosensitive activities mainly through the inhibition
      and reversal of IR-induced MET and ATM-Chk2 axis activities in glioblastoma.
      H1/pHGFK1 nanoparticles are a potential radiosensitiser and angiogenic inhibitor
      for glioblastoma treatment.

PMID- 29348488
TI  - Interferon-alpha enhances the antitumour activity of EGFR-targeted therapies by
      upregulating RIG-I in head and neck squamous cell carcinoma.
AB  - BACKGROUND: The epidermal growth factor receptor (EGFR)-targeted therapies have
      been tested in the clinic as treatments for head and neck squamous cell carcinoma
      (HNSCC). Owing to intrinsic or acquired resistance, EGFR-targeted therapies often
      lead to a low response rate and treatment failure. Interferon-alpha (IFNalpha) is
      a chemosensitising agent and multi-functional cytokine with a tumour inhibitory
      effect. However, the synergic effect of IFNalpha and EGFR-targeted therapies
      (erlotinib and nimotuzumab) and their mechanisms in HNSCC remain unclear.
      METHODS: The interactions between IFNalpha, erlotinib, and nimotuzumab were
      evaluated in vitro in HNSCC cells. The synergistic effect of IFNalpha (20 000 IU
      per day, s.c.), erlotinib (50 mg kg-1 per day, i.g.) and nimotuzumab (10 mg kg-1
      per day, i.p.) was further confirmed in vivo using HNSCC xenografts in nude mice.
      The upregulation of retinoic-acid inducible gene I (RIG-I) induced by IFNalpha
      and EGFR-targeted therapies and its mechanism were detected in vitro and in vivo.
      RESULTS: IFNalpha enhances the antitumour effects of erlotinib and nimotuzumab on
      HNSCC cells both in vitro and in vivo. Importantly, both IFNalpha and EGFR
      targeted therapies promote the expression of RIG-I by activating signal
      transducers and activators of transcription 1 (STAT1) in HNSCC cells. RIG-I
      knockdown reduced the sensitivity of HN4 and HN30 cells to IFNalpha, erlotinib,
      and nimotuzumab. Moreover, IFNalpha transcriptionally induced RIG-I expression in
      HNSCC cells through STAT1. CONCLUSIONS: IFNalpha enhances the effect of EGFR
      targeted therapies by upregulating RIG-I, and its expression may represent a
      predictor of the effectiveness of a combination treatment including IFNalpha in
      HNSCC.

PMID- 29348489
TI  - Which patients are not included in the English Cancer Waiting Times monitoring
      dataset, 2009-2013? Implications for use of the data in research.
AB  - BACKGROUND: Cancer waiting time targets are routinely monitored in England, but
      the Cancer Waiting Times monitoring dataset (CWT) does not include all eligible
      patients, introducing scope for bias. METHODS: Data from adults diagnosed in
      England (2009-2013) with colorectal, lung, or ovarian cancer were linked from CWT
      to cancer registry, mortality, and Hospital Episode Statistics data. We present
      demographic characteristics and net survival for patients who were and were not
      included in CWT. RESULTS: A CWT record was found for 82% of colorectal, 76% of
      lung, and 77% of ovarian cancer patients. Patients not recorded in CWT were more
      likely to be in the youngest or oldest age groups, have more comorbidities, have
      been diagnosed through emergency presentation, have late or missing stage, and
      have much poorer survival. CONCLUSIONS: Researchers and policy-makers should be
      aware of the limitations in the completeness and representativeness of CWT, and
      draw conclusions with appropriate caution.

PMID- 29348490
TI  - Robot-assisted radical prostatectomy vs laparoscopic and open retropubic radical
      prostatectomy: functional outcomes 18 months after diagnosis from a national
      cohort study in England.
AB  - BACKGROUND: Robot-assisted radical prostatectomy (RARP) has been rapidly adopted
      without robust evidence comparing its functional outcomes against laparoscopic
      radical prostatectomy (LRP) or open retropubic radical prostatectomy (ORP)
      approaches. This study compared patient-reported functional outcomes following
      RARP, LRP or ORP. METHODS: All men diagnosed with prostate cancer in England
      during April - October 2014 who underwent radical prostatectomy were identified
      from the National Prostate Cancer Audit and mailed a questionnaire 18 months
      after diagnosis. Group differences in patient-reported sexual, urinary, bowel and
      hormonal function (EPIC-26 domain scores) and generic health-related quality of
      life (HRQoL; EQ-5D-5L scores), with adjustment for patient and tumour
      characteristics, were estimated using linear regression. RESULTS: In all, 2219
      men (77.0%) responded; 1310 (59.0%) had RARP, 487 (21.9%) LRP and 422 (19.0%)
      ORP. RARP was associated with slightly higher adjusted mean EPIC-26 sexual
      function scores compared with LRP (3.5 point difference; 95% CI: 1.1-5.9,
      P=0.004) or ORP (4.0 point difference; 95% CI: 1.5-6.5, P=0.002), which did not
      meet the threshold for a minimal clinically important difference (10-12 points).
      There were no significant differences in other EPIC-26 domain scores or HRQoL.
      CONCLUSIONS: It is unlikely that the rapid adoption of RARP in the English NHS
      has produced substantial improvements in functional outcomes for patients.

PMID- 29348491
TI  - Order enables efficient electron-hole separation at an organic heterojunction
      with a small energy loss.
AB  - Donor-acceptor organic solar cells often show low open-circuit voltages (V OC)
      relative to their optical energy gap (E g) that limit power conversion
      efficiencies to ~12%. This energy loss is partly attributed to the offset between
      E g and that of intermolecular charge transfer (CT) states at the donor-acceptor
      interface. Here we study charge generation occurring in PIPCP:PC61BM, a system
      with a very low driving energy for initial charge separation (E g-E CT ~ 50 meV)
      and a high internal quantum efficiency (eta IQE ~ 80%). We track the strength of
      the electric field generated between the separating electron-hole pair by
      following the transient electroabsorption optical response, and find that while
      localised CT states are formed rapidly (<100 fs) after photoexcitation, free
      charges are not generated until 5 ps after photogeneration. In PIPCP:PC61BM,
      electronic disorder is low (Urbach energy <27 meV) and we consider that free
      charge separation is able to outcompete trap-assisted non-radiative recombination
      of the CT state.

PMID- 29348492
TI  - v-Src-driven transformation is due to chromosome abnormalities but not Src
      mediated growth signaling.
AB  - v-Src is the first identified oncogene product and has a strong tyrosine kinase
      activity. Much of the literature indicates that v-Src expression induces
      anchorage-independent and infinite cell proliferation through continuous
      stimulation of growth signaling by v-Src activity. Although all of v-Src
      expressing cells are supposed to form transformed colonies, low frequencies of v
      Src-induced colony formation have been observed so far. Using cells that exhibit
      high expression efficiencies of inducible v-Src, we show that v-Src expression
      causes cell-cycle arrest through p21 up-regulation despite ERK activation. v-Src
      expression also induces chromosome abnormalities and unexpected suppression of v
      Src expression, leading to p21 down-regulation and ERK inactivation. Importantly,
      among v-Src-suppressed cells, only a limited number of cells gain the ability to
      re-proliferate and form transformed colonies. Our findings provide the first
      evidence that v-Src-driven transformation is attributed to chromosome
      abnormalities, but not continuous stimulation of growth signaling, possibly
      through stochastic genetic alterations.

PMID- 29348493
TI  - DNA multi-bit non-volatile memory and bit-shifting operations using addressable
      electrode arrays and electric field-induced hybridization.
AB  - DNA has been employed to either store digital information or to perform parallel
      molecular computing. Relatively unexplored is the ability to combine DNA-based
      memory and logical operations in a single platform. Here, we show a DNA tri-level
      cell non-volatile memory system capable of parallel random-access writing of
      memory and bit shifting operations. A microchip with an array of individually
      addressable electrodes was employed to enable random access of the memory cells
      using electric fields. Three segments on a DNA template molecule were used to
      encode three data bits. Rapid writing of data bits was enabled by electric field
      induced hybridization of fluorescently labeled complementary probes and the data
      bits were read by fluorescence imaging. We demonstrated the rapid parallel
      writing and reading of 8 (23) combinations of 3-bit memory data and bit shifting
      operations by electric field-induced strand displacement. Our system may find
      potential applications in DNA-based memory and computations.

PMID- 29348494
TI  - Diurnal cycle and seasonal variation of cloud cover over the Tibetan Plateau as
      determined from Himawari-8 new-generation geostationary satellite data.
AB  - Analysis of cloud cover and its diurnal variation over the Tibetan Plateau (TP)
      is highly reliant on satellite data; however, the accuracy of cloud detection
      from both polar-orbiting and geostationary satellites over this area remains
      unclear. The new-generation geostationary Himawari-8 satellites provide high
      resolution spatial and temporal information about clouds over the Tibetan
      Plateau. In this study, the cloud detection of MODIS and AHI is investigated and
      validated against CALIPSO measurements. For AHI and MODIS, the false alarm rate
      of AHI and MODIS in cloud identification over the TP was 7.51% and 1.94%,
      respectively, and the cloud hit rate was 73.55% and 80.15%, respectively. Using
      hourly cloud-cover data from the Himawari-8 satellites, we found that at the
      monthly scale, the diurnal cycle in cloud cover over the TP tends to increase
      throughout the day, with the minimum and maximum cloud fractions occurring at
      10:00 a.m. and 18:00 p.m. local time. Due to the limited time resolution of polar
      orbiting satellites, the underestimation of MODIS daytime average cloud cover is
      approximately 4.00% at the annual scale, with larger biases during the spring
      (5.40%) and winter (5.90%).

PMID- 29348495
TI  - Preclinical evaluation of antitumor activity of the proteasome inhibitor MLN2238
      (ixazomib) in hepatocellular carcinoma cells.
AB  - Hepatocellular carcinoma (HCC) is one of the common malignancies and is an
      increasingly important cause of cancer death worldwide. Surgery, chemotherapy,
      and radiation therapy extend the 5-year survival limit in HCC patients by only
      6%. Therefore, there is a need to develop new therapeutic approaches for the
      treatment of this disease. The orally bioavailable proteasome inhibitor MLN2238
      (ixazomib) has been demonstrated to have anticancer activity. In the present
      study, we investigated the preclinical therapeutic efficacy of MLN2238 in HCC
      cells through in vitro and in vivo models, and examined its molecular mechanisms
      of action. MLN2238 inhibited cell viability in human HCC cells HepG2, Hep3B, and
      SNU475 in a time- and dose-dependent manner. Flow cytometry analysis demonstrated
      that MLN2238 induced G2/M cell cycle arrest and cellular apoptosis in HCC cells.
      Cell cycle arrest was associated with increased expression levels of p21 and p27.
      MLN2238-induced apoptosis was confirmed by caspase-3/7 activation, PARP cleavage
      and caspase-dependent beta-catenin degradation. In addition, MLN2238 activated ER
      stress genes in HCC cells and increased the expression of the stress-inducible
      gene nuclear protein-1. Furthermore, MLN2238 treatment induced upregulation of
      myeloid cell leukemia-1 (Mcl-1) protein, and Mcl-1 knockdown sensitized HCC cells
      to MLN2238 treatment, suggesting the contribution of Mcl-1 expression to MLN2238
      resistance. This result was also confirmed using the novel Mcl-1 small molecule
      inhibitor A1210477. Association of A1210477 and MLN2238 determined synergistic
      antitumor effects in HCC cells. Finally, in vivo orally administered MLN2238
      suppressed tumor growth of Hep3B cells in xenograft models in nude mice. In
      conclusion, our results offer hope for a new therapeutic opportunity in the
      treatment of HCC patients.

PMID- 29348497
TI  - RNA-binding proteins control gene expression and cell fate in the immune system.
AB  - RNA-binding proteins (RBPs) are essential for the development and function of the
      immune system. They interact dynamically with RNA to control its biogenesis and
      turnover by transcription-dependent and transcription-independent mechanisms. In
      this Review, we discuss the molecular mechanisms by which RBPs allow gene
      expression changes to occur at different speeds and to varying degrees, and which
      RBPs regulate the diversity of the transcriptome and proteome. These proteins are
      nodes for integration of transcriptional and signaling networks and are
      intimately linked to intermediary metabolism. They are essential components of
      regulatory feedback mechanisms that maintain immune tolerance and limit
      inflammation. The role of RBPs in malignancy and autoimmunity has led to their
      emergence as targets for the development of new therapeutic modalities.

PMID- 29348498
TI  - mTECs Aire on the side of caution.

PMID- 29348496
TI  - Natriuretic peptides promote glucose uptake in a cGMP-dependent manner in human
      adipocytes.
AB  - Robust associations between low plasma level of natriuretic peptides (NP) and
      increased risk of type 2 diabetes (T2D) have been recently reported in humans.
      Adipose tissue (AT) is a known target of NP. However it is unknown whether NP
      signalling in human AT relates to insulin sensitivity and modulates glucose
      metabolism. We here show in two European cohorts that the NP receptor guanylyl
      cyclase-A (GC-A) expression in subcutaneous AT was down-regulated as a function
      of obesity grade while adipose NP clearance receptor (NPRC) was up-regulated.
      Adipose GC-A mRNA level was down-regulated in prediabetes and T2D, and negatively
      correlated with HOMA-IR and fasting blood glucose. We show for the first time
      that NP promote glucose uptake in a dose-dependent manner. This effect is reduced
      in adipocytes of obese individuals. NP activate mammalian target of rapamycin
      complex 1/2 (mTORC1/2) and Akt signalling. These effects were totally abrogated
      by inhibition of cGMP-dependent protein kinase and mTORC1/2 by rapamycin. We
      further show that NP treatment favoured glucose oxidation and de novo lipogenesis
      independently of significant gene regulation. Collectively, our data support a
      role for NP in blood glucose control and insulin sensitivity by increasing
      glucose uptake in human adipocytes. This effect is partly blunted in obesity.

PMID- 29348499
TI  - ERAdP standing in the shadow of STING innate immune signaling.

PMID- 29348502
TI  - Stress-induced depression.

PMID- 29348501
TI  - Myocardial infarct inflammation.

PMID- 29348503
TI  - NKT cells aid antiviral responses.

PMID- 29348500
TI  - Myeloid-derived suppressor cells coming of age.
AB  - Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells
      generated during a large array of pathologic conditions ranging from cancer to
      obesity. These cells represent a pathologic state of activation of monocytes and
      relatively immature neutrophils. MDSCs are characterized by a distinct set of
      genomic and biochemical features, and can, on the basis of recent findings, be
      distinguished by specific surface molecules. The salient feature of these cells
      is their ability to inhibit T cell function and thus contribute to the
      pathogenesis of various diseases. In this Review, we discuss the origin and
      nature of these cells; their distinctive features; and their biological roles in
      cancer, infectious diseases, autoimmunity, obesity and pregnancy.

PMID- 29348504
TI  - Trials and Tribble-ations of tissue TRM cells.

PMID- 29348505
TI  - Antibiotics-immune system interactions.

PMID- 29348506
TI  - Macrophages: damage control.

PMID- 29348507
TI  - Stressed-out ROS take a silent death route.

PMID- 29348508
TI  - Adipose tissue TM cells.

PMID- 29348509
TI  - Triggering molecular assembly at the mesoscale for advanced Raman detection of
      proteins in liquid.
AB  - An advanced optofluidic system for protein detection based on Raman signal
      amplification via dewetting and molecular gathering within temporary mesoscale
      assemblies is presented. The evaporation of a microliter volume of protein
      solution deposited in a circular microwell precisely follows an outward-receding
      geometry. Herein the combination of liquid withdrawal with intermolecular
      interactions induces the formation of self-assembled molecular domains at the
      solid-liquid interface. Through proper control of the evaporation rate, amplitude
      of the assemblies and time for spectral collection at the liquid edge are
      extensively raised, resulting in a local enhancement and refinement of the Raman
      response, respectively. Further signal amplification is obtained by taking
      advantage of the intense local electromagnetic fields generated upon adding a
      plasmonic coating to the microwell. Major advantages of this optofluidic method
      lie in the obtainment of high-quality, high-sensitivity Raman spectra with
      detection limit down to sub-micromolar values. Peculiarly, the assembled proteins
      in the liquid edge region maintain their native-like state without displaying
      spectral changes usually occurring when dried drop deposits are considered.

PMID- 29348510
TI  - Genome and secretome analysis of Pochonia chlamydosporia provide new insight into
      egg-parasitic mechanisms.
AB  - Pochonia chlamydosporia infects eggs and females of economically important plant
      parasitic nematodes. The fungal isolates parasitizing different nematodes are
      genetically distinct. To understand their intraspecific genetic differentiation,
      parasitic mechanisms, and adaptive evolution, we assembled seven putative
      chromosomes of P. chlamydosporia strain 170 isolated from root-knot nematode eggs
      (~44 Mb, including 7.19% of transposable elements) and compared them with the
      genome of the strain 123 (~41 Mb) isolated from cereal cyst nematode. We focus on
      secretomes of the fungus, which play important roles in pathogenicity and fungus
      host/environment interactions, and identified 1,750 secreted proteins, with a
      high proportion of carboxypeptidases, subtilisins, and chitinases. We analyzed
      the phylogenies of these genes and predicted new pathogenic molecules. By
      comparative transcriptome analysis, we found that secreted proteins involved in
      responses to nutrient stress are mainly comprised of proteases and glycoside
      hydrolases. Moreover, 32 secreted proteins undergoing positive selection and 71
      duplicated gene pairs encoding secreted proteins are identified. Two duplicated
      pairs encoding secreted glycosyl hydrolases (GH30), which may be related to
      fungal endophytic process and lost in many insect-pathogenic fungi but exist in
      nematophagous fungi, are putatively acquired from bacteria by horizontal gene
      transfer. The results help understanding genetic origins and evolution of
      parasitism-related genes.

PMID- 29348511
TI  - Resonant plasma excitation by single-cycle THz pulses.
AB  - In this paper, an alternative perspective for the generation of millimetric high
      gradient resonant plasma waves is discussed. This method is based on the plasma
      wave excitation by energetic single-cycle THz pulses whose temporal length is
      comparable to the plasma wavelength. The excitation regime discussed in this
      paper is the quasi-nonlinear regime that can be achieved when the normalized
      vector potential of the driving THz pulse is on the order of unity. To
      investigate this regime and determine the strength of the excited electric
      fields, a Particle-In-Cell (PIC) code has been used. It has been found that by
      exploiting THz pulses with characteristics currently available in laboratory,
      longitudinal electron plasma waves with electric gradients up to hundreds MV/m
      can be obtained. The mm-size nature of the resonant plasma wave can be of great
      utility for an acceleration scheme in which high-brightness electron bunches are
      injected into the wave to undergo a strong acceleration. The long-size nature of
      the acceleration bucket with respect to the short length of the electron bunches
      can be handled in a more robust manner in comparison with the case when
      micrometric waves are employed.

PMID- 29348513
TI  - Publisher Correction: Functionalized Non-vascular Nitinol Stent via
      Electropolymerized Polydopamine Thin Film Coating Loaded with Bortezomib Adjunct
      to Hyperthermia Therapy.
AB  - A correction to this article has been published and is linked from the HTML
      version of this paper. The error has been fixed in the paper.

PMID- 29348512
TI  - CA1 and CA3 differentially support spontaneous retrieval of episodic contexts
      within human hippocampal subfields.
AB  - The hippocampus plays a critical role in spatial and episodic memory. Mechanistic
      models predict that hippocampal subfields have computational specializations that
      differentially support memory. However, there is little empirical evidence
      suggesting differences between the subfields, particularly in humans. To clarify
      how hippocampal subfields support human spatial and episodic memory, we developed
      a virtual reality paradigm where participants passively navigated through houses
      (spatial contexts) across a series of videos (episodic contexts). We then used
      multivariate analyses of high-resolution fMRI data to identify neural
      representations of contextual information during recollection. Multi-voxel
      pattern similarity analyses revealed that CA1 represented objects that shared an
      episodic context as more similar than those from different episodic contexts.
      CA23DG showed the opposite pattern, differentiating between objects encountered
      in the same episodic context. The complementary characteristics of these
      subfields explain how we can parse our experiences into cohesive episodes while
      retaining the specific details that support vivid recollection.

PMID- 29348514
TI  - 3D Imaging through Scatterers with Interferenceless Optical System.
AB  - Imaging through a scattering medium is a challenging task. We propose and
      demonstrate an interferenceless incoherent opto-digital technique for 3D imaging
      through a scatterer with a single lens and a digital camera. The light diffracted
      from a point object is modulated by a scattering mask. The modulated wavefront is
      projected on an image sensor using a spherical lens and the impulse response is
      recorded. An object is placed at the same axial location as the point object and
      another intensity pattern is recorded with identical experimental conditions and
      with the same scattering mask. The image of the object is reconstructed by a
      cross-correlation between a reconstructing function and the object hologram. For
      3D imaging, a library of reconstructing functions are created corresponding to
      different axial locations. The different planes of the object are reconstructed
      by a cross-correlation of the object hologram with the corresponding
      reconstructing functions.

PMID- 29348516
TI  - Evidence of the Zanclean megaflood in the eastern Mediterranean Basin.
AB  - The Messinian salinity crisis (MSC) - the most abrupt, global-scale environmental
      change since the end of the Cretaceous - is widely associated with partial
      desiccation of the Mediterranean Sea. A major open question is the way normal
      marine conditions were abruptly restored at the end of the MSC. Here we use
      geological and geophysical data to identify an extensive, buried and chaotic
      sedimentary body deposited in the western Ionian Basin after the massive
      Messinian salts and before the Plio-Quaternary open-marine sedimentary sequence.
      We show that this body is consistent with the passage of a megaflood from the
      western to the eastern Mediterranean Sea via a south-eastern Sicilian gateway.
      Our findings provide evidence for a large amplitude drawdown in the Ionian Basin
      during the MSC, support the scenario of a Mediterranean-wide catastrophic flood
      at the end of the MSC, and suggest that the identified sedimentary body is the
      largest known megaflood deposit on Earth.

PMID- 29348515
TI  - Genetic evidence for panmixia in a colony-breeding crater lake cichlid fish.
AB  - Fine-scaled genetic structuring, as seen for example in many lacustrine fish,
      typically relates to the patterns of migration, habitat use, mating system or
      other ecological factors. Because the same processes can also affect the
      propensity of population differentiation and divergence, assessments of species
      from rapidly speciating clades, or with particularly interesting ecological
      traits, can be especially insightful. For this study, we assessed the spatial
      genetic relationships, including the genetic evidence for sex-biased dispersal,
      in a colony-breeding cichlid fish, Amphilophus astorquii, endemic to Crater Lake
      Apoyo in Nicaragua, using 11 polymorphic microsatellite loci (n = 123 individuals
      from three colonies). We found no population structure in A. astorquii either
      within colonies (no spatial genetic autocorrelation, r ~0), or at the lake-wide
      level (pairwise population differentiation FST = 0-0.013 and no clustering), and
      there was no sex-bias (male and female AIc values bounded 0) to this lack of
      genetic structure. These patterns may be driven by the colony-breeding
      reproductive behaviour of A. astorquii. The results suggest that strong
      philopatry or spatial assortative mating are unlikely to explain the rapid
      speciation processes associated with the history of this species in Lake Apoyo.

PMID- 29348517
TI  - NDRG2 contributes to cisplatin sensitivity through modulation of BAK-to-Mcl-1
      ratio.
AB  - The downregulation of N-Myc downstream-regulated gene 2 (NDRG2) is known to be
      associated with the progression and poor prognosis of several cancers.
      Sensitivity to anti-cancer may be associated with a good prognosis in cancer
      patients, and NDRG2, which is induced by p53, sensitizes the cells to
      chemotherapy. However, the unique function of NDRG2 as an inducer of apoptosis
      under chemotreatment has not been sufficiently studied. In this study, we
      investigated the role of NDRG2 in chemo-sensitivity, focusing on cisplatin in
      U937 histiocytic lymphoma, which has the loss-of-functional mutation in p53.
      NDRG2 promoted the sensitivity to cisplatin through the modulation of the BAK-to
      Mcl-1 ratio. The degradation of Mcl-1 and increase in BAK were mediated by JNK
      activation and the eIF2alpha/p-eIF2alpha pathway, respectively, which depended on
      PKR activation in NDRG2-overexpressed U937 (U937-NDRG2) cells. NOX5 was highly
      expressed in U937-NDRG2 cells and contributed to ROS production after cisplatin
      treatment. ROS scavenging or NOX5-knockdown successfully inhibited the
      sensitivity of U937-NDRG2 cells to cisplatin. Taken together, these findings
      indicate that NDRG2 contributed to the increased sensitivity to ciplatin through
      the modulation of Bak-to-Mcl-1 ratio regulated by NOX5-ROS-PKR pathway;
      therefore, we suggest that NDRG2 may be a molecular target for improving the
      efficacy of drug treatment in cancer patients.

PMID- 29348518
TI  - Serum omega-3 Polyunsaturated Fatty Acids and Potential Influence Factors in
      Elderly Patients with Multiple Cardiovascular Risk Factors.
AB  - Recent clinical trials failed to demonstrate that omega-3 polyunsaturated fatty
      acid (PUFA) supplement reduced cardiovascular events, which contradicted previous
      evidence. However, serum omega-3 PUFA concentrations of participants remained
      unclear in those studies. We aimed to investigate the definite relationship
      between serum concentrations of omega-3 PUFAs and coronary artery disease (CAD),
      and to explore the potential influence factors of omega-3 PUFAs. We selected
      Chinese in-patients (n = 460) with multiple cardiovascular risk factors or an
      established diagnosis of CAD. Serum omega-3 PUFAs, including eicosapentaenoic
      acid (EPA) and docosahexaenoic acid (DHA), were measured by liquid chromatography
      mass spectrometry. Serum concentrations of omega-3 PUFAs in CAD patients were
      lower than that in patients with cardiovascular risk factors. Furthermore, high
      serum DHA concentration was an independent protective factor of CAD after
      adjustment for confounding factors (OR: 0.52, p = 0.014). Alcohol intake (p =
      0.036) and proton pump inhibitor (PPI) usage (p = 0.027) were associated with a
      decreased serum omega-3 PUFA concentration. We conclude that serum concentrations
      of omega-3 PUFAs may associate with a decreased CAD proportion, and DHA may serve
      as a protective factor of CAD. Serum omega-3 PUFA concentrations may be reduced
      by alcohol intake and certain drugs like PPIs.

PMID- 29348520
TI  - Discharge without alarm(s)!

PMID- 29348519
TI  - Guanylate Binding Protein 1 Inhibits Osteogenic Differentiation of Human
      Mesenchymal Stromal Cells Derived from Bone Marrow.
AB  - Guanylate Binding Proteins (GBPs) are a group of cytokine-inducible large
      guanosine triphosphatase. Previous studies have shown high expression of GBP1 in
      circulating monocytes of premenopausal subjects was correlated to extremely low
      peak bone mass, which is considered as an important determinant of osteoporosis.
      However, whether GBPs play a role in regulation of osteogenesis of mesenchymal
      stromal cells (MSCs) remains largely unknown. In the present study, we found that
      mRNA expression of GBP1 was highest among all the GBPs, and it was dramatically
      downregulated during osteogenic differentiation of human MSCs derived from bone
      marrow (hBM-MSCs). While siRNA-mediated knockdown of GBP1 promoted osteogenesis,
      overexpression of GBP1 suppressed osteogenesis of hBM-MSCs. Furthermore, we found
      GBP1 is required for expression of indoleamine 2,3 dioxygenase (IDO), Interleukin
      6 (IL-6) and IL-8 induced by treatment with Interferon-gamma (IFN-gamma).
      Depletion of GBP1 rescued the inhibited osteogenesis induced by IFN-gamma
      treatment, at least in part. Collectively, our findings indicate GBP1 inhibits
      osteogenic differentiation of MSCs, and inhibition of GBP1 expression may prevent
      development of osteoporosis and facilitate MSC-based bone regeneration.

PMID- 29348521
TI  - JBIR-150, a novel 20-membered polyene macrolactam from marine-derived
      Streptomyces sp. OPMA00071.
AB  - During the course of constructing a natural product library for drug screening
      consisting of microbial culture extracts originated from marine samples, we
      evaluated natural product components profiles via UPLC TOF-MS and routine
      biological tests for cytotoxic and antibiotic activities for all of the culture
      extract samples. By combination of chemical screening and biological activities,
      we succeeded in discovering a 20-membered macrolactam antibiotic subsequently
      designated JBIR-150 (1) from a marine-derived actinomycete identified as
      Streptomyces sp. that was isolated from an Okinawan marine sediment. The chemical
      structure of 1 was determined by interpreting NMR spectroscopic and mass
      spectrometric data. Compound 1 exhibited moderate cytotoxicity against MESO-1 and
      Jurkat cells.

PMID- 29348522
TI  - In vitro and in vivo antimicrobial activity of TS2037, a novel aminoglycoside
      antibiotic.
AB  - To overcome serious methicillin-resistant Staphylococcus aureus (MRSA) and
      Pseudomonas aeruginosa infections, we synthesized TS2037, 5,4"-diepi-arbekacin, a
      novel aminoglycoside antibiotic, and evaluated its biological properties. TS2037
      showed broad-range, as well as robust antibacterial activities against Gram
      positive and Gram-negative bacteria. The MIC50 and MIC90 of TS2037 against
      clinical isolates of MRSA (n = 54) were both 0.25 ug/mL, and no resistant strain
      was observed. The MIC50 and MIC90 of TS2037 against clinical isolates of P.
      aeruginosa (n = 54) were 1 and 4 ug/mL, respectively. TS2037 and arbekacin, anti
      MRSA aminoglycoside, were more stable against AAC(6')-APH(2"), aminoglycoside-6'
      N-acetyltransferase and 2"-O-phosphotransferase, produced by resistant S. aureus
      than gentamicin. Therapeutic efficacies of TS2037 in the mouse models of systemic
      infection with MRSA were superior to those of arbekacin, vancomycin, and
      linezolid. The efficacy of TS2037 against systemic infection caused by P.
      aeruginosa producing AAC(6')-II was superior to those of arbekacin and amikacin.
      In the nephrotoxicity risk screening, the release of free N-acetyl-beta-D
      glucosaminidase from the kidney epithelial cell line after treatment with TS2037
      at 2.5 and 5.0 MUM were 2.0 and 2.1 (U/L), respectively, which were about two
      times higher than those of arbekacin. In conclusion, TS2037 exhibited the most
      potent antibacterial activity among aminoglycosides tested against both MRSA and
      P. aeruginosa in vitro and in vivo, although its nephrotoxicity risk remains to
      be improved.

PMID- 29348523
TI  - Antibiotic resistance mutations induced in growing cells of Bacillus-related
      thermophiles.
AB  - Stress-induced mutagenesis can assist pathogens in generating drug-resistant
      cells during antibiotic therapy; however, if and how antibiotics induce
      mutagenesis in microbes remains poorly understood. A non-pathogenic thermophile,
      Geobacillus kaustophilus HTA426, efficiently produces derivative cells resistant
      to rifampicin and streptomycin via rpoB and rpsL mutations, respectively. Here,
      we examined this phenomenon to suggest a novel mutagenic mode induced by
      antibiotics. Fluctuation analysis indicated that mutations occurred via
      spontaneous mutations during culture. However, mutations were much more frequent
      in growing cells than stationary cells, and mutation sites were varied through
      cell growth. These observations suggested that growing cells induced mutagenesis
      in response to antibiotics. An in-frame deletion of mfd, which governs
      transcription-coupled repair to correct DNA lesions on the transcribed strand,
      caused mutations that were comparable between growing and stationary cells;
      therefore, the mutagenic mechanism was attributable to DNA repair defects where
      growing cells depressed mfd function. Mutations occurred more frequently at
      optimal growth temperatures for G. kaustophilus than at a higher growth
      temperature, suggesting that the mutagenesis relies on active cellular activities
      rather than high temperature-associated DNA damage. In addition, the mutagenesis
      may involve a mutagenic factor targeting these sites, in addition to mfd
      depression, because rpoB and rpsL mutations were dominant at thymine and guanine
      sites on the transcribed strand. A similar mutagenic profile was observed for
      other Geobacillus and thermophilic Bacillus species. This suggests that Bacillus
      related thermophiles commonly induce mutagenesis in response to rifampicin and
      streptomycin to produce resistant cells.

PMID- 29348524
TI  - Linearmycins are lytic membrane-targeting antibiotics.
AB  - The linearmycin family of polyketides was originally classified as antifungal
      metabolites. However, in addition to antifungal activity, we previously found
      that linearmycins cause cellular lysis and colony degradation of the Gram
      positive bacterium Bacillus subtilis. We recently showed that Streptomyces sp.
      strain Mg1 incorporates linearmycins into extracellular vesicles, which are
      capable of lysing B. subtilis. However, the mechanism of linearmycin-induced
      lysis was hitherto unexplored. Therefore, we sought to determine how linearmycin
      laden vesicles cause lysis. In this study, we found that linearmycins inhibited
      the growth of all Gram-positive bacteria that we tested, but lysis was limited to
      some Bacillus species. Next, we found that linearmycin-induced lysis occurred
      even when cellular metabolism and growth were inhibited, which suggested that
      linearmycins possess the intrinsic capacity to lyse cells, unlike cell-wall
      targeting antibiotics. We showed that linearmycin exposure caused changes
      consistent with rapid depolarization of the B. subtilis cytoplasmic membrane,
      which was correlated with a loss of viability. Finally, using liposomes as in
      vitro membrane models, we demonstrated that linearmycins are capable of
      disrupting lipid bilayers without any other cellular components. Taken together,
      our results strongly indicate that the cytoplasmic membrane is the direct
      antibacterial target of linearmycins.

PMID- 29348525
TI  - Cordybislactone, a stereoisomer of the 14-membered bislactone clonostachydiol,
      from the hopper pathogenic fungus Cordyceps sp. BCC 49294: revision of the
      absolute configuration of clonostachydiol.
AB  - Cordybislactone (3), a new stereoisomer of the 14-membered bislactone
      clonostachydiol, together with its open ring analog (4), was isolated from the
      hopper pathogenic fungus Cordyceps sp. BCC 49294. The relative and absolute
      configurations of 3 were determined by chemical derivatizations, including the
      modified Mosher's method. The stereochemistry of clonostachydiol was determined
      using the natural compound isolated from Xylaria sp. BCC 4297. The result
      revealed that the absolute configuration of clonostachydiol, previously
      determined by synthesis, should be revised to its enantiomer.

PMID- 29348526
TI  - Prodigiosin R2, a new prodigiosin from the roseophilin producer Streptomyces
      griseoviridis 2464-S5.
AB  - Roseophilin (2) is a unique prodigiosin-related compound produced by Streptomyces
      griseoviridis 2464-S5, and is characterized by a central furan ring and a
      bicyclic alkyl chain. During a search for biosynthetic intermediates of 2, a new
      metabolite designated prodigiosin R2 (1) was isolated from the culture of the
      roseophilin producer. The molecular formula of 1 was established as C27H35N3O by
      high-resolution FAB-MS. The structure of 1 was determined by NMR spectroscopic
      analyses as a prodigiosin derivative with the same bicyclic alkyl chain as 2.
      Prodigiosin R2 (1) showed potent cytotoxicity against HeLa human cervical
      carcinoma cells and HT1080 human fibrosarcoma cells with IC50s of 0.41 and 0.82
      MUM, respectively.

PMID- 29348527
TI  - The human muscarinic acetylcholine receptor antagonist, Dicyclomine targets
      signal transduction genes and inhibits the virulence factors in the human
      pathogen, Candida albicans.
AB  - Dicyclomine is a human muscarinic acetylcholine receptor antagonist used for the
      treatment of abdominal cramps. We are reporting here that dicyclomine can inhibit
      the in vitro growth and virulence factors of the human pathogen Candida albicans
      very effectively. Dicyclomine inhibited adhesion, early biofilm, mature biofilm,
      and planktonic growth. Yeast to hyphal form transition of C. albicans in various
      inducer media such as serum, proline, glucose, and N-acetylglucosamine was
      inhibited. Dicyclomine also could kill C. albicans cells within 15 min of
      exposure. Dicyclomine appears to inhibit the yeast to hyphal conversion by
      affecting signal transduction pathway. The expression of selected genes
      associated with yeast to hyphal form transition in serum in presence of
      dicyclomine was studied using real-time polymerase chain reaction (RtPCR). The
      RtPCR analysis showed that dicyclomine targets both cAMP pathway as well as MAPK
      cascade. Eight genes were upregulated. Out of these, three major upregulated
      genes were Bcy1, Tup1, and Mig1. Dicyclomine downregulated Ume6, Ece1, and Pde2
      genes which are involved in cAMP signaling pathway and also downregulated the DNA
      binding protein gene, Rfg1. Dicyclomine significantly upregulated the master
      negative regulator of hyphal formation, Tup1. Based on this study we suggest that
      the muscarinic acetylcholine receptor antagonist, dicyclomine could be
      repositioned as a potential anti-Candida albicans as well as anti-virulence
      agent.

PMID- 29348528
TI  - Agrocin 108 is a 5'-cytidine nucleotide bacteriocin containing a carbocyclic
      phosphoryl-ascorbate group.
AB  - Agrocin 108 is a 3'-O-beta-D-xylopyranosyl-cytidine-5'-O-phosphodiester of an
      ascorbate-carbocyclic cyclopentenone analogue, with bacteriocin-like properties.
      This bacteriocin exhibits orders of magnitude greater than the inhibition zone
      diameter towards the indicator strain than either ampicillin or streptomycin. It
      has been isolated from cultures of Rhizobium rhizogenes strain K108. The
      structure of the agrocin 108 without detail, has been previously published. We
      now report a detailed structure elucidation, including the hitherto undetermined
      residual 5'-phospho-diester fragment by a combination of 1D and 2D NMR studies at
      various pH values in H2O/D2O, high resolution MS, pKa determination, and chemical
      degradation.

PMID- 29348529
TI  - Two new lankacidin-related metabolites from Streptomyces sp. HS-NF-1178.
AB  - Two new lankacidin-related metabolites, 2,18-seco-lankacidinol A (1), 2,18-seco
      lankacidinol B (2) and a known compound, lankacidinol (3), were isolated from the
      fermentation broth of Streptomyces sp. HS-NF-1178. Their structures were
      determined on the basis of spectroscopic analysis, including 1D and 2D NMR
      techniques as well as ESI-MS and comparison with data from the literature. These
      two new compounds, especially compound 1, exhibited potent antitumor activity.

PMID- 29348530
TI  - Time inside the mutant selection window as a predictor of staphylococcal
      resistance to linezolid.
AB  - To explore if the time inside the mutant selection window (TMSW) is a reliable
      predictor of emergence of bacterial resistance to linezolid, mixed inocula of
      each of three methicillin-resistant Staphylococcus aureus strains (MIC of
      linezolid 2 MUg ml-1) and their previously selected resistant mutants (MIC 8 MUg
      ml-1) were exposed to linezolid pharmacokinetics using an in vitro dynamic model.
      In five-day treatments simulated over a wide range of the 24-h area under the
      concentration-time curve (AUC24) to the MIC ratio, mutants resistant to 4 * MIC
      of antibiotic were enriched in a TMSW-dependent manner. With each strain, TMSW
      relationships with the area under the bacterial mutant concentration-time curve
      (AUBCM) exhibited a hysteresis loop, with the upper portion corresponding to the
      time above the mutant prevention concentration (MPC; T>MPC) of 0 and the lower
      portion-to the T>MPC > 0. Using AUBCM related to the maximal value observed with
      a given strain (normalized AUBCM) at T>MPC > 0, a strain-independent sigmoid
      relationship was established between AUBCM and TMSW, as well as T>MPC (r2 0.99
      for both). AUC24/MIC and AUC24/MPC relationships with normalized AUBCM for
      combined data on the three studied S. aureus strains were bell-shaped (r2 0.85
      and 0.80, respectively). These findings suggest that TMSW at T>MPC > 0, T>MPC,
      AUC24/MIC and AUC24/MPC are useful bacterial strain-independent predictors of the
      emergence of staphylococcal resistance to linezolid.

PMID- 29348531
TI  - Isopentylated diphenyl ether derivatives from the fermentation products of an
      endophytic fungus Phomopsis fukushii.
AB  - Three new isopentylated diphenyl ethers, (1-3), together with two known
      isopentylated diphenyl ethers derivatives (4 and 5) were isolated from the
      fermentation products of an endophytic fungus Phomopsis fukushii. Their
      structures were elucidated by spectroscopic methods, including extensive 1D- and
      2D NMR techniques. Compounds 1-3 were evaluated for their anti-methicillin
      resistant Staphylococcus aureus (anti-MRSA) activity. The results showed that
      compounds 1-3 showed strong activity with diameter of inhibition zone (IZD) of
      21.8 +/- 2.4 mm, 16.8 +/- 2.2 mm, and 15.6 +/- 2.0 mm, respectively.

PMID- 29348533
TI  - Structured thermal surface for radiative camouflage.
AB  - Thermal camouflage has been successful in the conductive regime, where thermal
      metamaterials embedded in a conductive system can manipulate heat conduction
      inside the bulk. Most reported approaches are background-dependent and not
      applicable to radiative heat emitted from the surface of the system. A coating
      with engineered emissivity is one option for radiative camouflage, but only when
      the background has uniform temperature. Here, we propose a strategy for radiative
      camouflage of external objects on a given background using a structured thermal
      surface. The device is non-invasive and restores arbitrary background temperature
      distributions on its top. For many practical candidates of the background
      material with similar emissivity as the device, the object can thereby be
      radiatively concealed without a priori knowledge of the host conductivity and
      temperature. We expect this strategy to meet the demands of anti-detection and
      thermal radiation manipulation in complex unknown environments and to inspire
      developments in phononic and photonic thermotronics.

PMID- 29348532
TI  - Amygdala-orbitofrontal structural and functional connectivity in females with
      anxiety disorders, with and without a history of conduct disorder.
AB  - Conduct disorder (CD) and anxiety disorders (ADs) are often comorbid and both are
      characterized by hyper-sensitivity to threat, and reduced structural and
      functional connectivity between the amygdala and orbitofrontal cortex (OFC).
      Previous studies of CD have not taken account of ADs nor directly compared
      connectivity in the two disorders. We examined three groups of young women: 23
      presenting CD and lifetime AD; 30 presenting lifetime AD and not CD; and 17 with
      neither disorder (ND). Participants completed clinical assessments and diffusion
      weighted and resting-state functional MRI scans. The uncinate fasciculus was
      reconstructed using tractography and manual dissection, and structural measures
      extracted. Correlations of resting-state activity between amygdala and OFC seeds
      were computed. The CD + AD and AD groups showed similarly reduced structural
      integrity of the left uncinate compared to ND, even after adjusting for IQ,
      psychiatric comorbidity, and childhood maltreatment. Uncinate integrity was
      associated with harm avoidance traits among AD-only women, and with the
      interaction of poor anger control and anxiety symptoms among CD + AD women.
      Groups did not differ in functional connectivity. Reduced uncinate integrity
      observed in CD + AD and AD-only women may reflect deficient emotion regulation in
      response to threat, common to both disorders, while other neural mechanisms
      determine the behavioral response.

PMID- 29348534
TI  - Anti-cancer activities of allyl isothiocyanate and its conjugated silicon quantum
      dots.
AB  - Allyl isothiocyanate (AITC), a dietary phytochemical in some cruciferous
      vegetables, exhibits promising anticancer activities in many cancer models.
      However, previous data showed AITC to have a biphasic effect on cell viability,
      DNA damage and migration in human hepatoma HepG2 cells. Moreover, in a 3D co
      culture of HUVEC with pericytes, it inhibited tube formation at high doses but
      promoted this at low doses, which confirmed its biphasic effect on angiogenesis.
      siRNA knockdown of Nrf2 and glutathione inhibition abolished the stimulation
      effect of AITC on cell migration and DNA damage. The biological activity of a
      novel AITC-conjugated silicon quantum dots (AITC-SiQDs) has been investigated for
      the first time. AITC-SiQDs showed similar anti-cancer properties to AITC at high
      doses while avoiding the low doses stimulation effect. In addition, AITC-SiQDs
      showed a lower and long-lasting activation of Nrf2 translocation into nucleus
      which correlated with their levels of cellular uptake, as detected by the
      intrinsic fluorescence of SiQDs. ROS production could be one of the mechanisms
      behind the anti-cancer effect of AITC-SiQDs. These data provide novel insights
      into the biphasic effect of AITC and highlight the application of nanotechnology
      to optimize the therapeutic potential of dietary isothiocyanates in cancer
      treatment.

PMID- 29348535
TI  - Umbilical cord extracts improve osteoporotic abnormalities of bone marrow-derived
      mesenchymal stem cells and promote their therapeutic effects on ovariectomised
      rats.
AB  - Bone marrow-derived mesenchymal stem cells (BM-MSCs) are the most valuable source
      of autologous cells for transplantation and tissue regeneration to treat
      osteoporosis. Although BM-MSCs are the primary cells responsible for maintaining
      bone metabolism and homeostasis, their regenerative ability may be attenuated in
      postmenopausal osteoporosis patients. Therefore, we first examined potential
      abnormalities of BM-MSCs in an oestrogen-deficient rat model constructed by
      ovariectomy (OVX-MSCs). Cell proliferation, mobilisation, and regulation of
      osteoclasts were downregulated in OVX-MSCs. Moreover, therapeutic effects of OVX
      MSCs were decreased in OVX rats. Accordingly, we developed a new activator for BM
      MSCs using human umbilical cord extracts, Wharton's jelly extract supernatant
      (WJS), which improved cell proliferation, mobilisation and suppressive effects on
      activated osteoclasts in OVX-MSCs. Bone volume, RANK and TRACP expression of
      osteoclasts, as well as proinflammatory cytokine expression in bone tissues, were
      ameliorated by OVX-MSCs activated with WJS (OVX-MSCs-WJ) in OVX rats. Fusion and
      bone resorption activity of osteoclasts were suppressed in macrophage-induced and
      primary mouse bone marrow cell-induced osteoclasts via suppression of osteoclast
      specific genes, such as Nfatc1, Clcn7, Atp6i and Dc-stamp, by co-culture with OVX
      MSCs-WJ in vitro. In this study, we developed a new activator, WJS, which
      improved the functional abnormalities and therapeutic effects of BM-MSCs on
      postmenopausal osteoporosis.

PMID- 29348536
TI  - Surround inhibition can instantly be modulated by changing the attentional focus.
AB  - To further investigate the mechanism of surround inhibition (SI) and to determine
      whether adopting different attentional strategies might have an impact on the
      modulation of SI, the effects of adopting an external (EF) or internal focus of
      attention (IF) on SI and motor performance were investigated. While performing an
      index flexion with either an EF or IF, transcranial magnetic stimulation was
      applied at various time points in 14 healthy subjects. When adopting an EF
      compared to an IF, the results show an improved motor performance (+14.7% in MVC)
      and a reduced bEMG in the adjacent APB (-22.3%) during maximal index flexion.
      This was accompanied by an increased SI in the APB with an EF (+26.4%).
      Additionally, the decrease in bEMG correlated with the magnitude of SI in APB.
      The current results demonstrate an efficient way to modulate SI by changing the
      attentional focus in healthy subjects and might, at least in part, explain the
      better motor performance being associated with an EF. The present findings help
      to better understand the positive mechanisms of an EF on SI in the healthy motor
      system and may also points towards a treatment strategy in pathologies with
      disturbed SI such as focal hand dystonia.

PMID- 29348538
TI  - Broadband wave plates made by plasmonic metamaterials.
AB  - Although metamaterials wave-plates have been demonstrated previously, many of
      them suffer from the issue of narrow bandwidth since they typically rely on
      resonance principles and thus exhibit inevitable frequency dispersions. Here, we
      show that the dispersion of spoof surface plasmon (SSP) mode supported by a
      fishbone structure can be freely modulated by varying the structural parameters.
      This motivates us to establish a general strategy of building broadband wave
      plates by cascading two fishbone structures with different propagation constants
      of SSP modes. We derive a criterion under which the cross-polarization phase
      difference across the whole device can maintain at a nearly constant value over a
      wide frequency band, with frequency dispersions in the two fishbone structures
      cancelled out. As an illustration, we design and fabricate an efficient microwave
      quarter-wave plate and experimentally characterize its excellent polarization
      control performances over a broad frequency band (7-9.2 GHz). Our findings can
      stimulate making dispersion-controlled high-performance optical functional
      devices in different frequency domains.

PMID- 29348537
TI  - Radionuclides transform chemotherapeutics into phototherapeutics for precise
      treatment of disseminated cancer.
AB  - Most cancer patients succumb to disseminated disease because conventional
      systemic therapies lack spatiotemporal control of their toxic effects in vivo,
      particularly in a complicated milieu such as bone marrow where progenitor stem
      cells reside. Here, we demonstrate the treatment of disseminated cancer by
      photoactivatable drugs using radiopharmaceuticals. An orthogonal-targeting
      strategy and a contact-facilitated nanomicelle technology enabled highly
      selective delivery and co-localization of titanocene and radiolabelled
      fluorodeoxyglucose in disseminated multiple myeloma cells. Selective ablation of
      the cancer cells was achieved without significant off-target toxicity to the
      resident stem cells. Genomic, proteomic and multimodal imaging analyses revealed
      that the downregulation of CD49d, one of the dimeric protein targets of the
      nanomicelles, caused therapy resistance in small clusters of cancer cells.
      Similar treatment of a highly metastatic breast cancer model using human serum
      albumin-titanocene formulation significantly inhibited cancer growth. This
      strategy expands the use of phototherapy for treating previously inaccessible
      metastatic disease.

PMID- 29348539
TI  - Characterization of a Novel Tectivirus Phage Toil and Its Potential as an Agent
      for Biolipid Extraction.
AB  - : The oleaginous bacterium Rhodococcus opacus PD630 is metabolically diverse and
      can be cultivated on various renewable resources to serve as a sustainable
      triacylglycerol (TAG) feedstock for biodiesel production. Current methods for TAG
      extraction are costly, but infection of cultures by lytic bacteriophages (phages)
      may be a viable approach for achieving release of intracellular lipid from
      oleaginous bacteria such as R. opacus. This study reports the novel tectiviral
      phage Toil capable of releasing intracellular contents including a fluorescent
      protein marker and TAGs into the supernatant after phage infection of R. opacus
      PD631, a domesticated derivative of strain PD630. Phage Toil is placed in the
      Tectiviridae by its morphology, the presence of a lipid membrane, its genome
      architecture and the presence of terminal covalently-linked proteins. Toil is the
      first tectivirus capable of infecting a member of the Actinobacteria. Microscopy
      shows that infected cells do not undergo sudden lysis but instead maintain their
      original shape for several hours, with the cellular morphology gradually
      deteriorating. Approximately 30% of intracellular TAGs could be recovered from
      the culture supernatants of Toil-infected PD631 cells. Phage Toil has potential
      to be used as an agent in extraction of TAGs from oleaginous bacterium R. opacus.
      IMPORTANCE: This study reported the first tectivirus (Phage Toil) capable of
      infecting a member of the Actinobacteria. In this study, we showed that Phage
      Toil can infect oleaginous bacterium Rhodococcus opacus to release intracellular
      contents such as a fluorescent protein marker and TAG lipid granules, which can
      serve as a starting material for biodiesel production. This study demonstrates a
      new method to extract TAGs by using this phage. Additionally, Phage Toil can be a
      new model phage to advance knowledge regarding phage infection mechanisms in
      Rhodococcus and other mycolic acid-containing bacteria such as Mycobacterium.

PMID- 29348541
TI  - Neurodegenerative disease: TDP pathology leads to nuclear disruption.

PMID- 29348540
TI  - Human colorectal cancer-derived mesenchymal stem cells promote colorectal cancer
      progression through IL-6/JAK2/STAT3 signaling.
AB  - Mesenchymal stem cells (MSCs) have been reported to localize in colorectal
      carcinomas, and participate in the formation of the tumor microenvironment. They
      have recently been isolated from colorectal cancer tissues, and are implicated in
      the growth, invasion, and metastasis of cancer cells. However, the roles and
      detailed mechanisms associated with human colorectal cancer-derived MSCs (CC
      MSCs) have not been fully addressed. In this study, we found that CC-MSCs
      increased the migration and invasion of colorectal cancer cells and promoted the
      tumorigenesis of colorectal cancer through epithelial-to-mesenchymal transition
      (EMT) in vitro. We also found that CC-MSCs enhanced the growth and metastasis of
      colorectal cancer in vivo. Mechanistically, we determined that interleukin-6 (IL
      6) was the most highly expressed cytokine in the CC-MSC conditioned medium, and
      promoted the progression of colorectal cancer cells through IL-6/JAK2/STAT3
      signaling, which activated PI3K/AKT signaling. We used anti-IL-6 antibody to
      target IL-6. Collectively, these results reveal that the IL-6 secreted by CC-MSCs
      enhances the progression of colorectal cancer cells through IL-6/JAK2/STAT3
      signaling, and could provide a novel therapeutic or preventive target.

PMID- 29348542
TI  - Sensory systems: Bimodal cochlear nucleus stimulation alleviates tinnitus.

PMID- 29348543
TI  - Stroke in 2017: Intensive and extensive - advances in stroke management.

PMID- 29348544
TI  - Motor neuron disease: A prospective natural history study of type 1 spinal
      muscular atrophy.

PMID- 29348545
TI  - Motor neuron disease in 2017: Progress towards therapy in motor neuron disease.

PMID- 29348546
TI  - Epilepsy in 2017: Precision medicine drives epilepsy classification and therapy.

PMID- 29348547
TI  - High strength nanostructured Al-based alloys through optimized processing of
      rapidly quenched amorphous precursors.
AB  - We report the methods increasing both strength and ductility of aluminum alloys
      transformed from amorphous precursor. The mechanical properties of bulk samples
      produced by spark-plasma sintering (SPS) of amorphous Al-Ni-Co-Dy powders at
      temperatures above 673 K are significantly enhanced by in-situ crystallization of
      nano-scale intermetallic compounds during the SPS process. The spark plasma
      sintered Al84Ni7Co3Dy6 bulk specimens exhibit 1433 MPa compressive yield strength
      and 1773 MPa maximum strength together with 5.6% plastic strain, respectively.
      The addition of Dy enhances the thermal stability of primary fcc Al in the
      amorphous Al-TM -RE alloy. The precipitation of intermetallic phases by
      crystallization of the remaining amorphous matrix plays important role to
      restrict the growth of the fcc Al phase and contributes to the improvement of the
      mechanical properties. Such fully crystalline nano- or ultrafine-scale Al-Ni-Co
      Dy systems are considered promising for industrial application because their
      superior mechanical properties in terms of a combination of very high room
      temperature strength combined with good ductility.

PMID- 29348548
TI  - The global epidemiology of bladder cancer: a joinpoint regression analysis of its
      incidence and mortality trends and projection.
AB  - We tested the hypotheses that the global incidence of bladder cancer was
      increasing but its mortality was reducing and its incidence was positively
      correlated with country-specific socioeconomic development. We retrieved data on
      age-standardized incidence and mortality rates/100,000 from the GLOBOCAN database
      in 2012. Temporal patterns were examined for 39 countries from the Cancer
      Incidence in Five Continents volumes I-X and other national registries. We
      evaluated the correlation between the incidence/mortality rates and Human
      Development Index (HDI)/ logarithmic values of Gross Domestic Product per capita
      (GDP). The average annual percent change of the incidence and mortality rates in
      the most recent 10 years was examined by joinpoint regression analysis. The
      highest incidence rates were observed in Southern Europe, Western Europe and
      North America. The mortality rates were the highest in Western Asia and Northern
      Africa. The incidence was positively correlated with HDI (r = 0.66 [men]; r =
      0.50 [women]) and to a lesser extent logarithmic values of GDP per capita (r =
      0.60 [men]; r = 0.50 [women], all p < 0.01). Many European countries experienced
      incidence rise. A substantial mortality reduction was observed in most countries,
      yet increases in mortality rates were observed in the Philippines and Iceland.
      These findings identified countries where more preventive actions are required.

PMID- 29348549
TI  - Preoperative anemia in colorectal cancer: relationships with tumor
      characteristics, systemic inflammation, and survival.
AB  - Anemia is common in colorectal cancer (CRC) but its relationships with tumor
      characteristics, systemic inflammation, and survival have not been well
      characterized. In this study, blood hemoglobin levels and erythrocyte mean
      corpuscular volume (MCV) levels were measured in two independent cohorts of 148
      CRC patients and 208 CRC patients, and their correlation with patient and tumor
      characteristics, systemic inflammatory markers (modified Glasgow Prognostic
      Score: mGPS; serum levels of thirteen cytokines, C-reactive protein, albumin),
      and survival were analyzed. We found that anemia, most frequently normocytic,
      followed by microcytic, was present in 43% of the patients. Microcytic anemia was
      most commonly associated with proximal colon tumor location. Average MCV and
      blood hemoglobin levels were lower in tumors with high T-class. Low blood
      hemoglobin associated with systemic inflammation, including high mGPS and high
      serum levels of C-reactive protein and IL-8. Particularly, normocytic anemia
      associated with higher mGPS. Normocytic anemia associated with a tendency towards
      worse overall survival (multivariate hazard ratio 1.61, 95% confidence interval
      1.07-2.42, p = 0.023; borderline statistical significance considering multiple
      hypothesis testing). In conclusion, anemia in CRC patients is most frequently
      normocytic. Proximal tumor location is associated with predominantly microcytic
      anemia and systemic inflammation is associated with normocytic anemia.

PMID- 29348550
TI  - Bimolecular recombination in methylammonium lead triiodide perovskite is an
      inverse absorption process.
AB  - Photovoltaic devices based on metal halide perovskites are rapidly improving in
      efficiency. Once the Shockley-Queisser limit is reached, charge-carrier
      extraction will be limited only by radiative bimolecular recombination of
      electrons with holes. Yet, this fundamental process, and its link with material
      stoichiometry, is still poorly understood. Here we show that bimolecular charge
      carrier recombination in methylammonium lead triiodide perovskite can be fully
      explained as the inverse process of absorption. By correctly accounting for
      contributions to the absorption from excitons and electron-hole continuum states,
      we are able to utilise the van Roosbroeck-Shockley relation to determine
      bimolecular recombination rate constants from absorption spectra. We show that
      the sharpening of photon, electron and hole distribution functions significantly
      enhances bimolecular charge recombination as the temperature is lowered,
      mirroring trends in transient spectroscopy. Our findings provide vital
      understanding of band-to-band recombination processes in this hybrid perovskite,
      which comprise direct, fully radiative transitions between thermalized electrons
      and holes.

PMID- 29348551
TI  - Designable and dynamic single-walled stiff nanotubes assembled from sequence
      defined peptoids.
AB  - Despite recent advances in the assembly of organic nanotubes, conferral of
      sequence-defined engineering and dynamic response characteristics to the tubules
      remains a challenge. Here we report a new family of highly designable and dynamic
      nanotubes assembled from sequence-defined peptoids through a unique "rolling-up
      and closure of nanosheet" mechanism. During the assembly process, amorphous
      spherical particles of amphiphilic peptoid oligomers crystallize to form well
      defined nanosheets before folding to form single-walled nanotubes. These
      nanotubes undergo a pH-triggered, reversible contraction-expansion motion. By
      varying the number of hydrophobic residues of peptoids, we demonstrate tuning of
      nanotube wall thickness, diameter, and mechanical properties. Atomic force
      microscopy-based mechanical measurements show peptoid nanotubes are highly stiff
      (Young's Modulus ~13-17 GPa). We further demonstrate the precise incorporation of
      functional groups within nanotubes and their applications in water
      decontamination and cellular adhesion and uptake. These nanotubes provide a
      robust platform for developing biomimetic materials tailored to specific
      applications.

PMID- 29348552
TI  - TPGLDA: Novel prediction of associations between lncRNAs and diseases via lncRNA
      disease-gene tripartite graph.
AB  - Accumulating evidences have indicated that lncRNAs play an important role in
      various human complex diseases. However, known disease-related lncRNAs are still
      comparatively small in number, and experimental identification is time-consuming
      and labor-intensive. Therefore, developing a useful computational method for
      inferring potential associations between lncRNAs and diseases has become a hot
      topic, which can significantly help people to explore complex human diseases at
      the molecular level and effectively advance the quality of disease diagnostics,
      therapy, prognosis and prevention. In this paper, we propose a novel prediction
      of lncRNA-disease associations via lncRNA-disease-gene tripartite graph (TPGLDA),
      which integrates gene-disease associations with lncRNA-disease associations.
      Compared to previous studies, TPGLDA can be used to better delineate the
      heterogeneity of coding-non-coding genes-disease association and can effectively
      identify potential lncRNA-disease associations. After implementing the leave-one
      out cross validation, TPGLDA achieves an AUC value of 93.9% which demonstrates
      its good predictive performance. Moreover, the top 5 predicted rankings of lung
      cancer, hepatocellular carcinoma and ovarian cancer are manually confirmed by
      different relevant databases and literatures, affording convincing evidence of
      the good performance as well as potential value of TPGLDA in identifying
      potential lncRNA-disease associations. Matlab and R codes of TPGLDA can be found
      at following: https://github.com/USTC-HIlab/TPGLDA .

PMID- 29348553
TI  - Night eating model shows time-specific depression-like behavior in the forced
      swimming test.
AB  - The circadian clock system is associated with feeding and mood. Patients with
      night eating syndrome (NES) delay their eating rhythm and their mood declines
      during the evening and night, manifesting as time-specific depression. Therefore,
      we hypothesized that the NES feeding pattern might cause time-specific
      depression. We established new NES model by restricted feeding with high-fat diet
      during the inactive period under normal-fat diet ad libitum. The FST (forced
      swimming test) immobility time in the NES model group was prolonged only after
      lights-on, corresponding to evening and early night for humans. We examined the
      effect of the NES feeding pattern on peripheral clocks using PER2::LUCIFERASE
      knock-in mice and an in vivo monitoring system. Caloric intake during the
      inactive period would shift the peripheral clock, and might be an important
      factor in causing the time-specific depression-like behavior. In the NES model
      group, synthesis of serotonin and norepinephrine were increased, but utilization
      and metabolism of these monoamines were decreased under stress. Desipramine
      shortened some mice's FST immobility time in the NES model group. The present
      study suggests that the NES feeding pattern causes phase shift of peripheral
      clocks and malfunction of the monoamine system, which may contribute to the
      development of time-specific depression.

PMID- 29348554
TI  - Effects of CO2 enrichment on benthic primary production and inorganic nitrogen
      fluxes in two coastal sediments.
AB  - Ocean acidification may alter the cycling of nitrogen in coastal sediment and so
      the sediment-seawater nitrogen flux, an important driver of pelagic productivity.
      To investigate how this perturbation affects the fluxes of NOX-
      (nitrite/nitrate), NH4+ and O2, we incubated estuarine sand and subtidal silt in
      recirculating seawater with a CO2-adjusted pH of 8.1 and 7.9. During a 41-day
      incubation, the seawater kept at pH 8.1 lost 97% of its NOX- content but the
      seawater kept at pH 7.9 lost only 18%. Excess CO2 increased benthic
      photosynthesis. In the silt, this was accompanied by a reversal of the initial
      NOX- efflux into influx. The estuarine sand sustained its initial NOX- influx
      but, by the end of the incubation, released more NH4+ at pH 7.9 than at pH 8.1.
      We hypothesise that these effects share a common cause; excess CO2 increased the
      growth of benthic microalgae and so nutrient competition with ammonia oxidising
      bacteria (AOB). In the silt, diatoms likely outcompeted AOB for NH4+ and
      photosynthesis increased the dark/light fluctuations in the pore water
      oxygenation inhibiting nitrification and coupled nitrification/denitrification.
      If this is correct, then excess CO2 may lead to retention of inorganic nitrogen
      adding to the pressures of increasing coastal eutrophication.

PMID- 29348556
TI  - Puromycin labeling does not allow protein synthesis to be measured in energy
      starved cells.

PMID- 29348555
TI  - Novel Immunoinformatics Approaches to Design Multi-epitope Subunit Vaccine for
      Malaria by Investigating Anopheles Salivary Protein.
AB  - Malaria fever has been pervasive for quite a while in tropical developing regions
      causing high morbidity and mortality. The causal organism is a protozoan parasite
      of genus Plasmodium which spreads to the human host by the bite of hitherto
      infected female Anopheles mosquito. In the course of biting, a salivary protein
      of Anopheles helps in blood feeding behavior and having the ability to elicit the
      host immune response. This study represents a series of immunoinformatics
      approaches to design multi-epitope subunit vaccine using Anopheles mosquito
      salivary proteins. Designed subunit vaccine was evaluated for its immunogenicity,
      allergenicity and physiochemical parameters. To enhance the stability of vaccine
      protein, disulfide engineering was performed in a region of high mobility. Codon
      adaptation and in silico cloning was also performed to ensure the higher
      expression of designed subunit vaccine in E. coli K12 expression system. Finally,
      molecular docking and simulation study was performed for the vaccine protein and
      TLR-4 receptor, to determine the binding free energy and complex stability.
      Moreover, the designed subunit vaccine was found to induce anti-salivary immunity
      which may have the ability to prevent the entry of Plasmodium sporozoites into
      the human host.

PMID- 29348557
TI  - Sensitizing tumor cells to conventional drugs: HSP70 chaperone inhibitors, their
      selection and application in cancer models.
AB  - Hsp70 chaperone controls proteostasis and anti-stress responses in rapidly
      renewing cancer cells, making it an important target for therapeutic compounds.
      To date several Hsp70 inhibitors are presented with remarkable anticancer
      activity, however their clinical application is limited by the high toxicity
      towards normal cells. This study aimed to develop assays to search for the
      substances that reduce the chaperone activity of Hsp70 and diminish its
      protective function in cancer cells. On our mind the resulting compounds alone
      should be safe and function in combination with drugs widely employed in
      oncology. We constructed systems for the analysis of substrate-binding and
      refolding activity of Hsp70 and to validate the assays screened the substances
      representing most diverse groups of chemicals of InterBioScreen library. One of
      the inhibitors was AEAC, an N-amino-ethylamino derivative of colchicine, which
      toxicity was two-orders lower than that of parent compound. In contrast to
      colchicine, AEAC inhibited substrate-binding and refolding functions of Hsp70
      chaperones. The results of a drug affinity responsive target stability assay,
      microscale thermophoresis and molecular docking show that AEAC binds Hsp70 with
      nanomolar affinity. AEAC was found to penetrate C6 rat glioblastoma and B16 mouse
      melanoma cells and reduce there the function of the Hsp70-mediated refolding
      system. Although the cytotoxic and growth inhibitory activities of AEAC were
      minimal, the compound was shown to increase the antitumor efficiency of
      doxorubicin in tumor cells of both types. When the tumors were grown in animals,
      AEAC administration in combination with doxorubicin exerted maximal therapeutic
      effect prolonging animal survival by 10-15 days and reducing tumor growth rate by
      60%. To our knowledge, this is the first time that this approach to the high
      throughput analysis of chaperone inhibitors has been applied, and it can be
      useful in the search for drug combinations that are effective in the treatment of
      highly resistant tumors.

PMID- 29348558
TI  - Preparation of polyaniline/PbS core-shell nano/microcomposite and its application
      for photocatalytic H2 electrogeneration from H2O.
AB  - Lead sulfide (PbS) and polyaniline (PANI) nano/microparticles were prepared.
      Then, PANI/PbS core-shell nano/microcomposites (I, II, and III) were prepared by
      oxidative polymerization of different aniline concentrations (0.01, 0.03, and
      0.05 M), respectively, in the presence of 0.05 M PbS. FT-IR, XRD, SEM, HR-TEM,
      and UV-Vis analyses were carried out to characterize the samples. From the FT-IR
      data, there are redshifts in PbS and PANI nano/microparticles bands in comparison
      with PANI/PbS nano/microcomposites. The average crystallite sizes of PANI/PbS
      core-shell nano/microcomposites (I, II, and III) from XRD analyses were 46.5, 55,
      and 42.16 nm, respectively. From the optical analyses, nano/microcomposite (II)
      has the optimum optical properties with two band gaps values of 1.41 and 2.79 eV.
      Then, the nano/microcomposite (II) membrane electrode supported on ITO glass was
      prepared and applied on the photoelectrochemical (PEC) H2 generation from H2O.
      The characteristics current-voltage and current-time behaviors were measured at
      different wavelengths from 390 to 636 nm. Also, the incident photon-to-current
      conversion efficiency (IPCE) under monochromatic illumination condition was
      calculated. The optimum values for IPCE were 36.5 and 35.2% at 390 and 405 nm,
      respectively. Finally, a simple mechanism for PEC H2 generation from H2O using
      the nano/microcomposite (II) membrane electrode was mentioned.

PMID- 29348559
TI  - PLK1 protects against sepsis-induced intestinal barrier dysfunction.
AB  - Sepsis and sepsis-associated intestinal barrier dysfunction are common in
      intensive care units, with high mortality. The aim of this study is to
      investigate whether Polo-like kinase 1 (PLK1) ameliorates sepsis-induced
      intestinal barrier dysfunction in the intestinal epithelium. The mouse intestinal
      barrier was disrupted after Lipopolysaccharide (LPS) injection due to intestinal
      epithelial cell apoptosis and proliferation inhibition, accompanied by decreased
      PLK1. In HT-29 intestinal epithelial cells, LPS stimulation induced cell
      apoptosis and inhibited cell proliferation. Overexpression of PLK1 partly rescued
      the apoptosis and proliferation inhibition in HT29 cells caused by LPS. Finally,
      LPS stimulation promoted the reduction of PLK1, resulting in apoptosis and
      proliferation inhibition in intestinal epithelial cells, disrupting the
      intestinal epithelial barrier. These findings indicate that PLK1 might be a
      potential therapeutic target for the treatment of sepsis-induced intestinal
      barrier dysfunction.

PMID- 29348560
TI  - Discovery of a small-molecule protein kinase Cdelta-selective activator with
      promising application in colon cancer therapy.
AB  - Protein kinase C (PKC) isozymes play major roles in human diseases, including
      cancer. Yet, the poor understanding of isozymes-specific functions and the
      limited availability of selective pharmacological modulators of PKC isozymes have
      limited the clinical translation of PKC-targeting agents. Here, we report the
      first small-molecule PKCdelta-selective activator, the 7alpha-acetoxy-6beta
      benzoyloxy-12-O-benzoylroyleanone (Roy-Bz), which binds to the PKCdelta-C1
      domain. Roy-Bz potently inhibited the proliferation of colon cancer cells by
      inducing a PKCdelta-dependent mitochondrial apoptotic pathway involving caspase-3
      activation. In HCT116 colon cancer cells, Roy-Bz specifically triggered the
      translocation of PKCdelta but not other phorbol ester responsive PKCs. Roy-Bz
      caused a marked inhibition in migration of HCT116 cells in a PKCdelta-dependent
      manner. Additionally, the impairment of colonosphere growth and formation,
      associated with depletion of stemness markers, indicate that Roy-Bz also targets
      drug-resistant cancer stem cells, preventing tumor dissemination and recurrence.
      Notably, in xenograft mouse models, Roy-Bz showed a PKCdelta-dependent antitumor
      effect, through anti-proliferative, pro-apoptotic, and anti-angiogenic
      activities. Besides, Roy-Bz was non-genotoxic, and in vivo it had no apparent
      toxic side effects. Collectively, our findings reveal a novel promising
      anticancer drug candidate. Most importantly, Roy-Bz opens the way to a new era on
      PKC biology and pharmacology, contributing to the potential redefinition of the
      structural requirements of isozyme-selective agents, and to the re-establishment
      of PKC isozymes as feasible therapeutic targets in human diseases.

PMID- 29348561
TI  - Performance analysis of an adaptive optics system for free-space optics
      communication through atmospheric turbulence.
AB  - The performance of free-space optics communication (FSOC) is greatly degraded by
      atmospheric turbulence. Adaptive optics (AO) is an effective method for
      attenuating the influence. In this paper, the influence of the spatial and
      temporal characteristics of turbulence on the performance of AO in a FSOC system
      is investigated. Based on the Greenwood frequency (GF) and the ratio of receiver
      aperture diameter to atmospheric coherent length (D/r 0 ), the relationship
      between FSOC performance (CE) and AO parameters (corrected Zernike modes number
      and bandwidth) is derived for the first time. Then, simulations and experiments
      are conducted to analyze the influence of AO parameters on FSOC performance under
      different GF and D/r 0 . The simulation and experimental results show that, for
      common turbulence conditions, the number of corrected Zernike modes can be fixed
      at 35 and the bandwidth of the AO system should be larger than the GF.
      Measurements of the bit error rate (BER) for moderate turbulence conditions (D/r
      0  = 10, f G  = 60 Hz) show that when the bandwidth is two times that of GF, the
      average BER is decreased by two orders of magnitude compared with f G /f 3dB  =
      1. These results and conclusions can provide important guidance in the design of
      an AO system for FSOC.

PMID- 29348562
TI  - Non-marine palaeoenvironment associated to the earliest tetrapod tracks.
AB  - Opinions differ on whether the evolution of tetrapods (limbed vertebrates) from
      lobe-finned fishes was directly linked to terrestrialization. The earliest known
      tetrapod fossils, from the Middle Devonian (approximately 390 million years old)
      of Zachelmie Quarry in Poland, are trackways made by limbs with digits; they
      document a direct environmental association and thus have the potential to help
      answer this question. However, the tetrapod identity of the tracks has recently
      been challenged, despite their well-preserved morphology, on account of their
      great age and supposedly shallow marine (intertidal or lagoonal) depositional
      environment. Here we present a new palaeoenvironmental interpretation of the
      track-bearing interval from Zachelmie, showing that it represents a succession of
      ephemeral lakes with a restricted and non-marine biota, rather than a marginal
      marine environment as originally thought. This context suggests that the
      trackmaker was capable of terrestrial locomotion, consistent with the appendage
      morphology recorded by the footprints, and thus provides additional support for a
      tetrapod identification.

PMID- 29348563
TI  - Disruption of CXCR3 function impedes the development of Sjogren's syndrome-like
      xerostomia in non-obese diabetic mice.
AB  - The chemokine receptor CXCR3 plays an important role in T cell recruitment in
      various immune responses and autoimmune diseases. Expression of CXCR3 ligands,
      including CXCL9, CXCL10, and CXCL11, is elevated in the salivary glands of
      patients with Sjogren's syndrome (SS). To elucidate whether interaction between
      CXCR3 and its ligands is required for the development of SS, we administrated an
      anti-CXCR3 blocking antibody (CXCR3-173) to the non-obese diabetic (NOD) mice, a
      well-defined model of SS, during the stage prior to disease onset. Treatment with
      this anti-CXCR3 antibody significantly improved salivary secretion, indicating a
      remission of SS clinical manifestation. Anti-CXCR3 treatment did not affect the
      gross leukocyte infiltration of the submandibular glands (SMGs) as assessed by
      hematoxylin and eosin staining. However, flow cytometric analysis showed that
      anti-CXCR3 treatment markedly reduced the percentage of CXCR3+CD8 T and
      CXCR3+CD44+CD8 T cells, without affecting that of CXCR3+CD4 T and CXCR3+CD44+CD4
      T cells in the SMGs and submandibular lymph nodes, suggesting a preferential
      effect of this anti-CXCR3 treatment on CXCR3-expressing effector CD8 T cells.
      Meanwhile, SMG expression of inflammatory factor TNF-alpha was markedly
      diminished by anti-CXCR3 treatment. In accordance, anti-CXCR3 significantly
      enhanced SMG expression of tight junction protein claudin-1 and water channel
      protein aquaporin 5, two molecules that are crucial for normal salivary secretion
      and can be down-regulated by TNF-alpha. Taken together, these findings
      demonstrated that the interaction between the endogenous CXCR3 and its ligands
      plays a pro-inflammatory and pathogenic role in the development of SS-like
      xerostomia in the NOD mouse model.

PMID- 29348564
TI  - Inhibition of WNT/beta-catenin signaling under serum starvation and hypoxia
      induces adipocytic transdifferentiation in human leiomyoma cells.
AB  - Fatty metamorphosis is an uncommon alteration in uterine leiomyoma (i.e.,
      lipoleiomyoma), and the pathogenetic mechanisms underlying this phenomenon remain
      poorly understood. Because a conditional deletion of beta-catenin, a major
      transducer of the canonical Wingless/integrated (WNT) pathway, in the developing
      mouse uterus can induce adipogenesis in the myometrium, it is hypothesized that
      inhibition of the WNT/beta-catenin signaling may be also involved in the
      development of fat cells within uterine leiomyoma. In the current study, which
      was performed to address this point, intracytoplasmic lipid droplets were
      detectable in cultured human leiomyoma cells by treatment with a potent tankyrase
      inhibitor, XAV939, which antagonizes beta-catenin, in a serum-starved culture
      medium without additional adipogenesis-inducing agents or supplements, and showed
      increasing accumulation in a time-dependent manner. In addition, the induction of
      fat cells was greatly enhanced under hypoxic conditions (i.e., 2.5% O2)
      recapitulating the local in vivo situation of uterine leiomyoma-in comparison to
      that under normoxic conditions (i.e., 21% O2). The marker genes of differentiated
      fat cells such as ADIPOQ and PLIN were highly expressed in leiomyoma cells that
      were treated with XAV939 under hypoxia and serum starvation, whereas the
      immunohistochemical expression of desmin-a cytoskeletal protein representing
      smooth muscle differentiation-was downregulated, which appears in line with the
      switch in differentiation. The results of our study suggest that the inhibition
      of canonical WNT/beta-catenin signaling under the stress due to hypoxia and serum
      starvation can initiate adipocytic transdifferentiation or metaplasia in human
      uterine leiomyoma cells, which is potentially related to the development of
      lipoleiomyoma.

PMID- 29348565
TI  - An in vitro system of autologous lymphocytes culture that allows the study of
      homeostatic proliferation mechanisms in human naive CD4 T-cells.
AB  - The size of peripheral T-cell pool is kept constant throughout life. However, a
      decline in lymphocyte numbers is a feature of several human disorders, in which
      fast and slow homeostatic proliferation play a crucial role. Several in vitro and
      in vivo models have been developed to study such processes. Nevertheless, self-
      and commensal- antigens, well-known triggers of homeostatic proliferation, have
      not been examined in these models. We have designed an in vitro culture of human
      T-cells exposed to rIL7 and autologous antigen-presenting cells (aAPC) that
      allows the simultaneous characterization of the different types of homeostatic
      proliferation. Using our model, we first confirmed that both rIL7 and aAPC are
      survival signals ultimately leading to homeostatic proliferation. In addition, we
      explored the modulation of different anti-apoptotic, proliferative, activation
      and homing markers during fast and slow homeostatic proliferation. Finally,
      different subsets of Treg were generated during homeostatic proliferation in our
      model. In summary, our in vitro system is able to simultaneously reproduce both
      types of homeostatic proliferation of human naive CD4 T-cells, and allows the
      characterization of these processes. Our in vitro system is a useful tool to
      explore specific features of human homeostatic proliferation in different human
      lymphopenia-related disorders and could be used as a cell therapy approach.

PMID- 29348566
TI  - Phosphorylation of ULK1 by AMPK is essential for mouse embryonic stem cell self
      renewal and pluripotency.
AB  - Autophagy is a catabolic process to degrade both damaged organelles and
      aggregated proteins in somatic cells. We have recently identified that autophagy
      is an executor for mitochondrial homeostasis in embryonic stem cell (ESC), and
      thus contribute to stemness regulation. However, the regulatory and functional
      mechanisms of autophagy in ESC are still largely unknown. Here we have shown that
      activation of ULK1 by AMPK is essential for ESC self-renewal and pluripotency.
      Dysfunction of Ulk1 decreases the autophagic flux in ESC, leading to compromised
      self-renewal and pluripotency. These defects can be rescued by reacquisition of
      wild-type ULK1 and ULK1(S757A) mutant, but not ULK1(S317A, S555A and S777A) and
      kinase dead ULK1(K46I) mutant. These data indicate that phosphorylation of ULK1
      by AMPK, but not mTOR, is essential for stemness regulation in ESC. The findings
      highlight a critical role for AMPK-dependent phosphorylation of ULK1 pathway to
      maintain ESC self-renewal and pluripotency.

PMID- 29348567
TI  - Optical magnetism in planar metamaterial heterostructures.
AB  - Harnessing artificial optical magnetism has previously required complex two- and
      three-dimensional structures, such as nanoparticle arrays and split-ring
      metamaterials. By contrast, planar structures, and in particular dielectric/metal
      multilayer metamaterials, have been generally considered non-magnetic. Although
      the hyperbolic and plasmonic properties of these systems have been extensively
      investigated, their assumed non-magnetic response limits their performance to
      transverse magnetic (TM) polarization. We propose and experimentally validate a
      mechanism for artificial magnetism in planar multilayer metamaterials. We also
      demonstrate that the magnetic properties of high-index dielectric/metal
      hyperbolic metamaterials can be anisotropic, leading to magnetic hyperbolic
      dispersion in certain frequency regimes. We show that such systems can support
      transverse electric polarized interface-bound waves, analogous to their TM
      counterparts, surface plasmon polaritons. Our results open a route for tailoring
      optical artificial magnetism in lithography-free layered systems and enable us to
      generalize the plasmonic and hyperbolic properties to encompass both linear
      polarizations.

PMID- 29348568
TI  - Medial preoptic area in mice is capable of mediating sexually dimorphic behaviors
      regardless of gender.
AB  - The medial preoptic area (mPOA) differs between males and females in nearly all
      species examined to date, including humans. Here, using fiber photometry
      recordings of Ca2+ transients in freely behaving mice, we show ramping activities
      in the mPOA that precede and correlate with sexually dimorphic display of male
      typical mounting and female-typical pup retrieval. Strikingly, optogenetic
      stimulation of the mPOA elicits similar display of mounting and pup retrieval in
      both males and females. Furthermore, by means of recording, ablation, optogenetic
      activation, and inhibition, we show mPOA neurons expressing estrogen receptor
      alpha (Esr1) are essential for the sexually biased display of these behaviors.
      Together, these results underscore the shared layout of the brain that can
      mediate sex-specific behaviors in both male and female mice and provide an
      important functional frame to decode neural mechanisms governing sexually
      dimorphic behaviors in the future.

PMID- 29348569
TI  - GenomeLandscaper: Landscape analysis of genome-fingerprints maps assessing
      chromosome architecture.
AB  - Assessing correctness of an assembled chromosome architecture is a central
      challenge. We create a geometric analysis method (called GenomeLandscaper) to
      conduct landscape analysis of genome-fingerprints maps (GFM), trace large-scale
      repetitive regions, and assess their impacts on the global architectures of
      assembled chromosomes. We develop an alignment-free method for phylogenetics
      analysis. The human Y chromosomes (GRCh.chrY, HuRef.chrY and YH.chrY) are
      analysed as a proof-of-concept study. We construct a galaxy of genome
      fingerprints maps (GGFM) for them, and a landscape compatibility among relatives
      is observed. But a long sharp straight line on the GGFM breaks such a landscape
      compatibility, distinguishing GRCh38p1.chrY (and throughout GRCh38p7.chrY) from
      GRCh37p13.chrY, HuRef.chrY and YH.chrY. We delete a 1.30-Mbp target segment to
      rescue the landscape compatibility, matching the antecedent GRCh37p13.chrY. We re
      locate it into the modelled centromeric and pericentromeric region of
      GRCh38p10.chrY, matching a gap placeholder of GRCh37p13.chrY. We decompose it
      into sub-constituents (such as BACs, interspersed repeats, and tandem repeats)
      and trace their homologues by phylogenetics analysis. We elucidate that most
      examined tandem repeats are of reasonable quality, but the BAC-sized repeats,
      173U1020C (176.46 Kbp) and 5U41068C (205.34 Kbp), are likely over-repeated. These
      results offer unique insights into the centromeric and pericentromeric regions of
      the human Y chromosomes.

PMID- 29348570
TI  - Systematic in vivo evaluation of the time-dependent inflammatory response to
      steel and Teflon insulin infusion catheters.
AB  - Continuous subcutaneous insulin infusion (CSII) catheters are considered the weak
      link of insulin pump therapy. Wear-time considerably varies between patients and
      the choice of catheter material is based on personal preferences rather than
      scientific facts. Therefore, we systematically assessed and quantified the
      inflammatory tissue response to steel versus Teflon CSII catheters over a maximum
      wear-time of 7 days in swine. Tissue surrounding catheters was analysed using
      histopathology and quantitative real-time PCR. The area of inflammation increased
      significantly over time independent of material which was confirmed by an
      increase in CD68 expression and an increase in mononuclear and neutrophil cell
      infiltrate around the catheters. We observed substantially higher fibrin
      deposition (p < 0.05) around steel on day 4 of wear-time. IL-6 gene expression
      increased within 24 hours after insertion, returned to normal levels around
      Teflon (p < 0.05) but remained high around steel (p < 0.05). IL-10 and TGF-beta
      levels did not resolve over time, indicating impaired wound healing. In
      conclusion, there was a major temporal effect in the acute inflammatory response
      to CSII catheters but we found little difference between materials. This study
      setup presents a robust tool for the systematic analysis of the tissue response
      to CSII catheters.

PMID- 29348571
TI  - High resolution time series reveals cohesive but short-lived communities in
      coastal plankton.
AB  - Because microbial plankton in the ocean comprise diverse bacteria, algae, and
      protists that are subject to environmental forcing on multiple spatial and
      temporal scales, a fundamental open question is to what extent these organisms
      form ecologically cohesive communities. Here we show that although all taxa
      undergo large, near daily fluctuations in abundance, microbial plankton are
      organized into clearly defined communities whose turnover is rapid and sharp. We
      analyze a time series of 93 consecutive days of coastal plankton using a
      technique that allows inference of communities as modular units of interacting
      taxa by determining positive and negative correlations at different temporal
      frequencies. This approach shows both coordinated population expansions that
      demarcate community boundaries and high frequency of positive and negative
      associations among populations within communities. Our analysis thus highlights
      that the environmental variability of the coastal ocean is mirrored in sharp
      transitions of defined but ephemeral communities of organisms.

PMID- 29348572
TI  - Areca nut extracts mobilize calcium and release pro-inflammatory cytokines from
      various immune cells.
AB  - Betel nut consumption has significant implications for the public health
      globally, as the wide-spread habit of Areca chewing throughout Asia and the
      Pacific is associated with a high prevalence of oral carcinoma and other
      diseases. Despite a clear causal association of betel nut chewing and oral
      mucosal diseases, the biological mechanisms that link Areca nut-contained
      molecules, inflammation and cancer remain underexplored. In this study we show
      that the whole Areca nut extract (ANE) is capable of mobilizing Ca2+ in various
      immune cell lines. Interestingly, none of the four major alkaloids or a range of
      other known constituents of Areca nut were able to induce such Ca2+ signals,
      suggesting that the active components might represent novel or so far
      unappreciated chemical structures. The separation of ANE into aqueous and organic
      fractions has further revealed that the calcium-mobilizing molecules are
      exclusively present in the aqueous extract. In addition, we found that these
      calcium signals are associated with the activation of several immune cell lines
      as shown by the release of pro-inflammatory cytokines and increased cell
      proliferation. These results indicate that calcium-mobilizing molecules present
      in the aqueous fraction of the Areca nut may critically contribute to the
      inflammatory disorders affecting betel nut chewers.

PMID- 29348574
TI  - Full-body physical therapy evaluation for pre- and post-hematopoietic cell
      transplant patients and the need for a modified rehabilitation musculoskeletal
      specific grading system for chronic graft-versus-host disease.

PMID- 29348573
TI  - Exendin-4-encapsulated dissolving microneedle arrays for efficient treatment of
      type 2 diabetes.
AB  - Dissolving microneedles (DMNs) are microscopic needles capable of delivering
      encapsulated compounds and releasing them into the skin in a minimally invasive
      manner. Most studies indicate that encapsulating therapeutics in DMNs is an
      efficacious approach; however, the importance of evaluating the activity of
      encapsulated compounds, during the fabrication process, has not been examined in
      detail. Conducting an analysis of thermal, chemical, and physical stress factors,
      including temperature, pH, and the interaction of the polymer and therapeutics
      mixture during preparation, is essential for retaining the activity of
      encapsulated therapeutics during and after fabrication. Here, we optimised the
      thermal, chemical, and physical parameters for the fabrication of exendin-4 (Ex
      4)-encapsulated DMNs (Ex-4 DMNs). Ex-4, a peptide agonist of glucagon-like
      peptide (GLP) receptor, is used for glycaemic control in patients with type 2
      diabetes. Our findings indicate that optimising the parameters involved in DMN
      fabrication retained the activity of Ex-4 by up to 98.3 +/- 1.5%. Ex-4 DMNs
      reduced the blood-glucose level in diabetic mice with efficiency similar to that
      of a subcutaneous injection. We believe that this study paves way for the
      commercialisation of an efficient and minimally invasive treatment for patients
      with type 2 diabetes.

PMID- 29348575
TI  - Quantitative optical nanophysiology of Ca2+ signaling at inner hair cell active
      zones.
AB  - Ca2+ influx triggers the release of synaptic vesicles at the presynaptic active
      zone (AZ). A quantitative characterization of presynaptic Ca2+ signaling is
      critical for understanding synaptic transmission. However, this has remained
      challenging to establish at the required resolution. Here, we employ confocal and
      stimulated emission depletion (STED) microscopy to quantify the number (20-330)
      and arrangement (mostly linear 70 nm * 100-600 nm clusters) of Ca2+ channels at
      AZs of mouse cochlear inner hair cells (IHCs). Establishing STED Ca2+ imaging, we
      analyze presynaptic Ca2+ signals at the nanometer scale and find confined
      elongated Ca2+ domains at normal IHC AZs, whereas Ca2+ domains are spatially
      spread out at the AZs of bassoon-deficient IHCs. Performing 2D-STED fluorescence
      lifetime analysis, we arrive at estimates of the Ca2+ concentrations at
      stimulated IHC AZs of on average 25 uM. We propose that IHCs form bassoon
      dependent presynaptic Ca2+-channel clusters of similar density but scalable
      length, thereby varying the number of Ca2+ channels amongst individual AZs.

PMID- 29348576
TI  - Redundancy of protein disulfide isomerases in the catalysis of the inactivating
      disulfide switch in A Disintegrin and Metalloprotease 17.
AB  - A Disintegrin and Metalloprotease 17 (ADAM17) can cause the fast release of
      growth factors and inflammatory mediators from the cell surface. Its activity has
      to be turned on which occurs by various stimuli. The active form can be
      inactivated by a structural change in its ectodomain, related to the pattern of
      the formed disulphide bridges. The switch-off is executed by protein disulfide
      isomerases (PDIs) that catalyze an isomerization of two disulfide bridges and
      thereby cause a disulfide switch. We demonstrate that the integrity of the CGHC
      motif within the active site of PDIs is indispensable. In particular, no major
      variation is apparent in the activities of the two catalytic domains of PDIA6.
      The affinities between PDIA1, PDIA3, PDIA6 and the targeted domain of ADAM17 are
      all in the nanomolar range and display no significant differences. The redundancy
      between PDIs and their disulfide switch activity in ectodomains of transmembrane
      proteins found in vitro appears to be a basic characteristic. However, different
      PDIs might be required in vivo for disulfide switches in different tissues and
      under different cellular and physiological situations.

PMID- 29348577
TI  - Targeting B cell receptor signalling in cancer: preclinical and clinical
      advances.
AB  - B cell receptor (BCR) signalling is crucial for normal B cell development and
      adaptive immunity. BCR signalling also supports the survival and growth of
      malignant B cells in patients with B cell leukaemias or lymphomas. The mechanism
      of BCR pathway activation in these diseases includes continuous BCR stimulation
      by microbial antigens or autoantigens present in the tissue microenvironment,
      activating mutations within the BCR complex or downstream signalling components
      and ligand-independent tonic BCR signalling. The most established agents
      targeting BCR signalling are Bruton tyrosine kinase (BTK) inhibitors and PI3K
      isoform-specific inhibitors, and their introduction into the clinic is rapidly
      changing how B cell malignancies are treated. B cells and BCR-related kinases,
      such as BTK, also play a role in the microenvironment of solid tumours, such as
      squamous cell carcinoma and pancreatic cancer, and therefore targeting B cells or
      BCR-related kinases may have anticancer activity beyond B cell malignancies.

PMID- 29348579
TI  - Structural basis of SALM5-induced PTPdelta dimerization for synaptic
      differentiation.
AB  - SALM5, a synaptic adhesion molecule implicated in autism, induces presynaptic
      differentiation through binding to the LAR family receptor protein tyrosine
      phosphatases (LAR-RPTPs) that have been highlighted as presynaptic hubs for
      synapse formation. The mechanisms underlying SALM5/LAR-RPTP interaction remain
      unsolved. Here we report crystal structures of human SALM5 LRR-Ig alone and in
      complex with human PTPdelta Ig1-3 (MeA-). Distinct from other LAR-RPTP ligands,
      SALM5 mainly exists as a dimer with LRR domains from two protomers packed in an
      antiparallel fashion. In the 2:2 heterotetrameric SALM5/PTPdelta complex, a SALM5
      dimer bridges two separate PTPdelta molecules. Structure-guided mutations and
      heterologous synapse formation assays demonstrate that dimerization of SALM5 is
      prerequisite for its functionality in inducing synaptic differentiation. This
      study presents a structural template for the SALM family and reveals a mechanism
      for how a synaptic adhesion molecule directly induces cis-dimerization of LAR
      RPTPs into higher-order signaling assembly.

PMID- 29348580
TI  - The epibiotic life of the cosmopolitan diatom Fragilariopsis doliolus on
      heterotrophic ciliates in the open ocean.
AB  - Diatoms are a diverse and ecologically important group of phytoplankton. Although
      most species are considered free living, several are known to interact with other
      organisms within the plankton. Detailed imaging and molecular characterization of
      any such partnership is, however, limited, and an appraisal of the large-scale
      distribution and ecology of such consortia was never attempted. Here, observation
      of Tara Oceans samples from the Benguela Current led to the detection of an
      epibiotic association between a pennate diatom and a tintinnid ciliate. We
      identified the diatom as Fragilariopsis doliolus that possesses a unique feature
      to form barrel-shaped chains, associated with seven different genera of
      tintinnids including five previously undescribed associations. The organisms were
      commonly found together in the Atlantic and Pacific Ocean basins, and live
      observations of the interaction have been recorded for the first time. By
      combining confocal and scanning electron microscopy of individual consortia with
      the sequencing of high-resolution molecular markers, we analyzed their
      distribution in the global ocean, revealing morpho-genetically distinct tintinnid
      haplotypes and biogeographically structured diatom haplotypes. The diatom was
      among the most abundant in the global ocean. We show that the consortia were
      particularly prevalent in nutrient-replete conditions, rich in potential
      predators. These observations support the hypothesis of a mutualistic symbiosis,
      wherein diatoms acquire increased motility and tintinnids benefit from
      silicification through increased protection, and highlight that such associations
      may be more prevalent than currently appreciated.

PMID- 29348578
TI  - A matter of life and death: stem cell survival in tissue regeneration and tumour
      formation.
AB  - In recent years, great strides have been made in our understanding of how stem
      cells (SCs) govern tissue homeostasis and regeneration. The inherent longevity of
      SCs raises the possibility that the unique protective mechanisms in these cells
      might also be involved in tumorigenesis. In this Opinion article, we discuss how
      SCs are protected throughout their lifespan, focusing on quiescent behaviour, DNA
      damage response and programmed cell death. We briefly examine the roles of adult
      SCs and progenitors in tissue repair and tumorigenesis and explore how signals
      released from dying or dormant cells influence the function of healthy or
      aberrant SCs. Important insight into the mechanisms that regulate SC death and
      survival, as well as the 'legacy' imparted by departing cells, may unlock novel
      avenues for regenerative medicine and cancer therapy.

PMID- 29348581
TI  - Identifying metabolic pathways for production of extracellular polymeric
      substances by the diatom Fragilariopsis cylindrus inhabiting sea ice.
AB  - Diatoms are significant primary producers in sea ice, an ephemeral habitat with
      steep vertical gradients of temperature and salinity characterizing the ice
      matrix environment. To cope with the variable and challenging conditions, sea ice
      diatoms produce polysaccharide-rich extracellular polymeric substances (EPS) that
      play important roles in adhesion, cell protection, ligand binding and as organic
      carbon sources. Significant differences in EPS concentrations and chemical
      composition corresponding to temperature and salinity gradients were present in
      sea ice from the Weddell Sea and Eastern Antarctic regions of the Southern Ocean.
      To reconstruct the first metabolic pathway for EPS production in diatoms, we
      exposed Fragilariopsis cylindrus, a key bi-polar diatom species, to simulated sea
      ice formation. Transcriptome profiling under varying conditions of EPS production
      identified a significant number of genes and divergent alleles. Their complex
      differential expression patterns under simulated sea ice formation was aligned
      with physiological and biochemical properties of the cells, and with field
      measurements of sea ice EPS characteristics. Thus, the molecular complexity of
      the EPS pathway suggests metabolic plasticity in F. cylindrus is required to cope
      with the challenging conditions of the highly variable and extreme sea ice
      habitat.

PMID- 29348582
TI  - Nanostructured titanium surfaces exhibit recalcitrance towards Staphylococcus
      epidermidis biofilm formation.
AB  - Titanium-based implants are ubiquitous in the healthcare industries and often
      suffer from bacterial attachment which results in infections. An innovative
      method of reducing bacterial growth is to employ nanostructures on implant
      materials that cause contact-dependent cell death by mechanical rupture of
      bacterial cell membranes. To achieve this, we synthesized nanostructures with
      different architectures on titanium surfaces using hydrothermal treatment
      processes and then examined the growth of Staphylococcus epidermidis on these
      surfaces. The structure obtained after a two-hour hydrothermal treatment
      (referred to as spear-type) showed the least bacterial attachment at short times
      but over a period of 6 days tended to support the formation of thick biofilms. By
      contrast, the structure obtained after a three-hour hydrothermal treatment
      (referred to as pocket-type) was found to delay biofilm formation up to 6 days
      and killed 47% of the initially attached bacteria by penetrating or compressing
      the bacteria in between the network of intertwined nano-spears. The results point
      to the efficacy of pocket-type nanostructure in increasing the killing rate of
      individual bacteria and potentially delaying longer-term biofilm formation.

PMID- 29348583
TI  - Rapid updating of spatial working memory across saccades.
AB  - Each time we make an eye movement, positions of objects on the retina change. In
      order to keep track of relevant objects their positions have to be updated. The
      situation becomes even more complex if the object is no longer present in the
      world and has to be held in memory. In the present study, we used saccadic
      curvature to investigate the time-course of updating a memorized location across
      saccades. Previous studies have shown that a memorized location competes with a
      saccade target for selection on the oculomotor map, which leads to saccades
      curving away from it. In our study participants performed a sequence of two
      saccades while keeping a location in memory. The trajectory of the second saccade
      was used to measure when the memorized location was updated after the first
      saccade. The results showed that the memorized location was rapidly updated with
      the eyes curving away from its spatial coordinates within 130 ms after the first
      eye movement. The time-course of updating was comparable to the updating of an
      exogenously attended location, and depended on how well the location was
      memorized.

PMID- 29348584
TI  - Quail egg homogenate alleviates food allergy induced eosinophilic esophagitis
      like disease through modulating PAR-2 transduction pathway in peanut sensitized
      mice.
AB  - The present pharmacotherapy for eosinophilic esophagitis (EoE) fundamentally
      depend on inhaled corticosteroids. Despite the fact that oral intake of topical
      steroids can be successful in restricting EoE-related inflammation, there are
      concerns with respect to the long term utilization of steroids, especially in
      kids. In the current research, we assess the effect of quail egg, which is
      reportedly a known serine protease inhibitor, on symptomatology and immune
      responses in a peanut-sensitized mouse model of food allergy induced EoE. Daily
      oral treatment with quail egg attenuated mice symptomatology and immune response.
      Treatment with quail egg inhibited antigen-prompted increments in mouse tryptase
      and eosinophil cationic protein (ECP) in serum and eosinophil in inflamed tissues
      like oesophagus, lung, and digestive system. Quail egg treatment resulted in
      decreased antibody specific IgE and IgG1 and a variety of inflammatory genes that
      were abnormally expressed in EoE. Other effects included increased IL-10,
      decreased PAR-2 activation and NF-kB p65 in inflamed tissues. Our results suggest
      that quail egg treatment may have therapeutic potential in attenuating the
      symptoms of food allergy induced EoE like disease through regulating PAR-2
      downstream pathway by blocking the activation of the transcription factor NF-kB
      p65 activity.

PMID- 29348585
TI  - A surrogate reporter system for multiplexable evaluation of CRISPR/Cas9 in
      targeted mutagenesis.
AB  - Engineered nucleases in genome editing manifest diverse efficiencies at different
      targeted loci. There is therefore a constant need to evaluate the mutation rates
      at given loci. T7 endonuclease 1 (T7E1) and Surveyor mismatch cleavage assays are
      the most widely used methods, but they are labour and time consuming, especially
      when one must address multiple samples in parallel. Here, we report a surrogate
      system, called UDAR (Universal Donor As Reporter), to evaluate the efficiency of
      CRISPR/Cas9 in targeted mutagenesis. Based on the non-homologous end-joining
      (NHEJ)-mediated knock-in strategy, the UDAR-based assay allows us to rapidly
      evaluate the targeting efficiencies of sgRNAs. With one-step transfection and
      fluorescence-activated cell sorting (FACS) analysis, the UDAR assay can be
      completed on a large scale within three days. For detecting mutations generated
      by the CRISPR/Cas9 system, a significant positive correlation was observed
      between the results from the UDAR and T7E1 assays. Consistently, the UDAR assay
      could quantitatively assess bleomycin- or ICRF193-induced double-strand breaks
      (DSBs), which suggests that this novel strategy is broadly applicable to
      assessing the DSB-inducing capability of various agents. With the increasing
      impact of genome editing in biomedical studies, the UDAR method can significantly
      benefit the evaluation of targeted mutagenesis, especially for high-throughput
      purposes.

PMID- 29348586
TI  - Analogues of Disulfides from Allium stipitatum Demonstrate Potent Anti-tubercular
      Activities through Drug Efflux Pump and Biofilm Inhibition.
AB  - Disulfides from Allium stipitatum, commonly known as Persian shallot, were
      previously reported to possess antibacterial properties. Analogues of these
      compounds, produced by S-methylthiolation of appropriate thiols using S-methyl
      methanethiosulfonate, exhibited antimicrobial activity, with one compound
      inhibiting the growth of Mycobacterium tuberculosis at 17 uM (4 mg L-1) and other
      compounds inhibiting Escherichia coli and multi-drug-resistant (MDR)
      Staphylococcus aureus at concentrations ranging between 32-138 uM (8-32 mg L-1).
      These compounds also displayed moderate inhibitory effects on Klebsiella and
      Proteus species. Whole-cell phenotypic bioassays such as the spot-culture growth
      inhibition assay (SPOTi), drug efflux inhibition, biofilm inhibition and
      cytotoxicity assays were used to evaluate these compounds. Of particular note was
      their ability to inhibit mycobacterial drug efflux and biofilm formation, while
      maintaining a high selectivity towards M. tuberculosis H37Rv. These results
      suggest that methyl disulfides are novel scaffolds which could lead to the
      development of new drugs against tuberculosis (TB).

PMID- 29348588
TI  - Two-color second-order sideband generation in an optomechanical system with a two
      level system.
AB  - Second-order sideband generation in an optomechanical system with the coupling
      between a mechanical resonator and a two-level system is discussed beyond the
      conventional linearized description of optomechanical interactions. The features
      of two-color second-order sideband generation are demonstrated in this hybrid
      system. We discovery that the switch between one- and two-color second-order
      sideband generation is easily realized by shifting the detuning between the
      control field and the cavity field or the transition frequency of the two-level
      system. The efficiency of two-color second-order sideband generation increases
      monotonously with the control field strength. The coupling strength between the
      mechanical resonator and the two-level system plays a decisive role in the
      appearance of the two-color second-order sidebands. The two-color second-order
      sideband generation may provide measurement with higher precision in new degrees
      of freedom.

PMID- 29348587
TI  - Comparative analyses of fecal microbiota in Chinese isolated Yao population,
      minority Zhuang and rural Han by 16sRNA sequencing.
AB  - The gut microbiome in humans is associated with geography, diet, lifestyles and
      so on, but its relationship with some isolated populations is not clear. We used
      the 16sRNA technique to sequence the fecal microbiome in the Chinese isolated Yao
      population and compared it with the major minority Zhuang and the major ethnic
      Han populations living in the same rural area. Information about diet frequency
      and health status and routine serum measurements were collected. The unweighted
      UniFrac principal coordinates analysis showed significant structural differences
      in fecal microbiota among the three ethnic groups. Statistically significant
      differences were observed in the community richness estimator (chaos) and the
      diversity estimator (Shannon) among the three groups. At the genus level, the
      fecal samples of the isolated Yao population presented the lowest relative
      abundance of the Megamonas genus, which was potentially related to the high
      frequency of bean consumption in the diet. Two enterotypes were identified in the
      overall fecal microbiota in the three populations. In the isolated Yao
      population, a higher Bacteroides abundance was observed, but the Prevotella
      abundance decreased with increased alcohol consumption.

PMID- 29348589
TI  - Novel Miniature Membrane Active Lipopeptidomimetics against Planktonic and
      Biofilm Embedded Methicillin-Resistant Staphylococcus aureus.
AB  - Escalating multidrug resistance and highly evolved virulence mechanisms have
      aggravated the clinical menace of methicillin-resistant Staphylococcus aureus
      (MRSA) infections. Towards development of economically viable staphylocidal
      agents here we report eight structurally novel tryptophan-arginine template based
      peptidomimetics. Out of the designed molecules, three lipopeptidomimetics (S-6, S
      7 and S-8) containing 12-amino dodecanoic acid exhibited cell selectivity and
      good to potent activity against clinically relevant pathogens MRSA, methicillin
      resistant Staphylococcus epidermidis and vancomycin-resistant Enterococcus
      faecium (MIC: 1.4-22.7 MUg/mL). Mechanistically, the active peptidomimetics
      dissipated membrane potential and caused massive permeabilization on MRSA
      concomitant with loss of viability. Against stationary phase MRSA under nutrient
      depleted conditions, active peptidomimetics S-7 and S-8 achieved > 6 log
      reduction in viability upon 24 h incubation while both S-7 (at 226 MUg/mL) and S
      8 (at 28 MUg/mL) also destroyed 48 h mature MRSA biofilm causing significant
      decrease in viability (p < 0.05). Encouragingly, most active peptidomimetic S-8
      maintained efficacy against MRSA in presence of serum/plasma while exhibiting no
      increase in MIC over 17 serial passages at sub-MIC concentrations implying
      resistance development to be less likely. Therefore, we envisage that the current
      template warrants further optimization towards the development of cell selective
      peptidomimetics for the treatment of device associated MRSA infections.

PMID- 29348590
TI  - The theoretical molecular weight of NaYF 4 :RE upconversion nanoparticles.
AB  - Upconversion nanoparticles (UCNPs) are utilized extensively for biomedical
      imaging, sensing, and therapeutic applications, yet the molecular weight of UCNPs
      has not previously been reported. Herein, we present a theory based upon the
      crystal structure of UCNPs to estimate the molecular weight of UCNPs: enabling
      insight into UCNP molecular weight for the first time. We estimate the
      theoretical molecular weight of various UCNPs reported in the literature,
      predicting that spherical NaYF4 UCNPs ~ 10 nm in diameter will be ~1 MDa (i.e.
      106 g/mol), whereas UCNPs ~ 45 nm in diameter will be ~100 MDa (i.e. 108 g/mol).
      We also predict that hexagonal crystal phase UCNPs will be of greater molecular
      weight than cubic crystal phase UCNPs. Additionally we find that a Gaussian UCNP
      diameter distribution will correspond to a lognormal UCNP molecular weight
      distribution. Our approach could potentially be generalised to predict the
      molecular weight of other arbitrary crystalline nanoparticles: as such, we
      provide stand-alone graphic user interfaces to calculate the molecular weight
      both UCNPs and arbitrary crystalline nanoparticles. We expect knowledge of UCNP
      molecular weight to be of wide utility in biomedical applications where reporting
      UCNP quantity in absolute numbers or molarity will be beneficial for inter-study
      comparison and repeatability.

PMID- 29348591
TI  - Relapsing-Remitting Multiple Sclerosis diagnosis from cerebrospinal fluids via
      Fourier transform infrared spectroscopy coupled with multivariate analysis.
AB  - Multiple sclerosis (MS) is a chronic, progressive, inflammatory and degenerative
      disease of central nervous system. Here, we aimed to develop a method for
      differential diagnosis of Relapsing-Remitting MS (RRMS) and clinically isolated
      syndrome (CIS) patients, as well as to identify CIS patients who will progress to
      RRMS, from cerebrospinal fluid (CSF) by infrared (IR) spectroscopy and
      multivariate analysis. Spectral analyses demonstrated significant differences in
      the molecular contents, especially in the lipids and Z conformation of DNA of CSF
      from CIS, CIS to RRMS transformed (TCIS) and RRMS groups. These changes enables
      the discrimination of diseased groups and controls (individuals with no
      neurological disease) from each other using hierarchical cluster and principal
      component analysis. Some CIS samples were consistently clustered in RRMS class,
      which may indicate that these CIS patients potentially will transform to RRMS
      over time. Z-DNA band at 795 cm-1 that is existent only in diseased groups and
      significant increase in carbonyl amount, decrease in amideI/amide II and
      lipid/protein ratios observed only for RRMS groups can be used as diagnostic
      biomarkers. The results of the present study shed light on the early diagnosis of
      RRMS by IR spectroscopy complemented with multivariate analysis tools.

PMID- 29348592
TI  - Stingless Bee Larvae Require Fungal Steroid to Pupate.
AB  - The larval stage of the stingless bee Scaptotrigona depilis must consume a
      specific brood cell fungus in order to continue development. Here we show that
      this fungus is a member of the genus Zygosaccharomyces and provides essential
      steroid precursors to the developing bee. Insect pupation requires ecdysteroid
      hormones, and as insects cannot synthesize sterols de novo, they must obtain
      steroids in their diet. Larval in vitro culturing assays demonstrated that
      consuming ergosterol recapitulates the developmental effects on S. depilis as
      ingestion of Zygosaccharomyces sp. cells. Thus, we determined the molecular
      underpinning of this intimate mutualistic symbiosis. Phylogenetic analyses showed
      that similar cases of bee-Zygosaccharomyces symbiosis may exist. This
      unprecedented case of bee-fungus symbiosis driven by steroid requirement brings
      new perspectives regarding pollinator-microbiota interaction and preservation.

PMID- 29348593
TI  - Temporal diabetes-induced biochemical changes in distinctive layers of mouse
      retina.
AB  - To discover the mechanisms underlying the progression of diabetic retinopathy
      (DR), a more comprehensive understanding of the biomolecular processes in
      individual retinal cells subjected to hyperglycemia is required. Despite
      extensive studies, the changes in the biochemistry of retinal layers during the
      development of DR are not well known. In this study, we aimed to determine a more
      detailed understanding of the natural history of DR in Akita/+ (type 1 diabetes
      model) male mice with different duration of diabetes. Employing label-free
      spatially resolved Fourier transform infrared (FT-IR) chemical imaging engaged
      with multivariate analysis enabled us to identify temporal-dependent reproducible
      biomarkers of the individual retinal layers from mice with 6 weeks,12 weeks, 6
      months, and 10 months of age. We report, for the first time, the nature of the
      biochemical alterations over time in the biochemistry of distinctive retinal
      layers namely photoreceptor retinal layer (PRL), inner nuclear layer (INL), and
      plexiform layers (OPL, IPL). Moreover, we present the molecular factors
      associated with the changes in the protein structure and cellular lipids of
      retinal layers induced by different duration of diabetes. Our paradigm provides a
      new conceptual framework for a better understanding of the temporal cellular
      changes underlying the progression of DR.

PMID- 29348594
TI  - Myelination of Purkinje axons is critical for resilient synaptic transmission in
      the deep cerebellar nucleus.
AB  - The roles of myelin in maintaining axonal integrity and action potential (AP)
      propagation are well established, but its role in synapse maintenance and
      neurotransmission remains largely understudied. Here, we investigated how
      Purkinje axon myelination regulates synaptic transmission in the Purkinje to deep
      cerebellar nuclei (DCN) synapses using the Long Evans Shaker (LES) rat, which
      lacks compact myelin and thus displays severe locomotion deficits. DCN neurons
      fired spontaneous action potentials (APs), whose frequencies were dependent on
      the extent of myelin. In the LES cerebellum with severe myelin deficiency, DCN
      neurons were hyper-excitable, exhibiting spontaneous AP firing at a much higher
      frequency compared to those from wild type (LE) and heterozygote (LEHet) rats.
      The hyper-excitability in LES DCN neurons resulted from reduced inhibitory
      GABAergic inputs from Purkinje cells to DCN neurons. Corresponding with
      functional alterations including failures of AP propagation, electron microscopic
      analysis revealed anatomically fewer active zones at the presynaptic terminals of
      Purkinje cells in both LEHet and LES rats. Taken together, these studies suggest
      that proper axonal myelination critically regulates presynaptic terminal
      structure and function and directly impacts synaptic transmission in the Purkinje
      cell-DCN cell synapse in the cerebellum.

PMID- 29348595
TI  - On the Angular Distribution of the H+Li2 Cross Sections: a Converged Time
      Independent Quantum Scattering Study.
AB  - A thorough time-independent quantum scattering study is performed on a benchmark
      potential energy surface for the H+Li2 reaction at the fundamental electronic
      state. Integral and differential cross sections are calculated along with thermal
      rate coefficients until convergence is reached. Our findings show that
      vibrational and rotational excitations of the reactant hinder reactivity, though
      for the latter a considerable reaction promotion was spotted as we increase the
      reactant rotational quantum number until the critical value of j = 4. Such a
      promotion then begins to retract, eventually becoming an actual inhibition for
      larger j. In a straightforward manner, the concept of time-independent methods
      implemented in this study allowed this accurate state-to-state analysis.
      Furthermore, a nearly isotropic behaviour of the scattering is noted to take
      place from the angular point of view. Remarkably, our computational protocol is
      ideally suited to yield converged thermal rate coefficients, revealing a non
      Arrhenius pattern and showing that J-shifting approach fails to describe this
      particular reaction. Our results, when compared to previous and independent ones,
      reinforce the latest theoretical reference for future validation in the
      experimental field.

PMID- 29348596
TI  - Dynamics of Tree Species Diversity in Unlogged and Selectively Logged Malaysian
      Forests.
AB  - Selective logging that is commonly conducted in tropical forests may change tree
      species diversity. In rarely disturbed tropical forests, locally rare species
      exhibit higher survival rates. If this non-random process occurs in a logged
      forest, the forest will rapidly recover its tree species diversity. Here we
      determined whether a forest in the Pasoh Forest Reserve, Malaysia, which was
      selectively logged 40 years ago, recovered its original species diversity
      (species richness and composition). To explore this, we compared the dynamics of
      secies diversity between unlogged forest plot (18.6 ha) and logged forest plot
      (5.4 ha). We found that 40 years are not sufficient to recover species diversity
      after logging. Unlike unlogged forests, tree deaths and recruitments did not
      contribute to increased diversity in the selectively logged forests. Our results
      predict that selectively logged forests require a longer time at least than our
      observing period (40 years) to regain their diversity.

PMID- 29348597
TI  - Author Correction: Short-Course, High-Dose Rifampicin Achieves Wolbachia
      Depletion Predictive of Curative Outcomes in Preclinical Models of Lymphatic
      Filariasis and Onchocerciasis.
AB  - A correction to this article has been published and is linked from the HTML
      version of this paper. The error has been fixed in the paper.

PMID- 29348598
TI  - Increased diversity with reduced "diversity evenness" of tumor infiltrating T
      cells for the successful cancer immunotherapy.
AB  - To facilitate the optimization of cancer immunotherapy lacking immune-related
      adverse events, we performed TCR repertoire analysis of tumor-infiltrating CD8+ T
      cells in B16 melanoma-bearing mice receiving anti-PD-1, anti-CTLA-4, anti-4-1BB,
      anti-CD4 or a combination of anti-PD-1 and 4-1BB antibodies. Although CD8+ T
      cells in the tumor were activated and expanded to a greater or lesser extent by
      these therapies, tumor growth suppression was achieved only by anti-PD-1, anti-PD
      1/4-1BB combined, or by anti-CD4 treatment, but not by anti-CTLA-4 or anti-4-1BB
      monotherapy. Increased CD8+ T cell effector function and TCR diversity with
      enrichment of certain TCR clonotypes in the tumor was associated with anti-tumor
      effects. In contrast, polyclonal activation of T-cells in the periphery was
      associated with tissue damage. Thus, optimal combination therapy increases TCR
      diversity with extended activation of selective CD8+ T-cells specifically in the
      tumor but not in the periphery. Incorporation of the concept of evenness for the
      TCR diversity is proposed.

PMID- 29348599
TI  - In situ formation of artificial moth-eye structure by spontaneous nano-phase
      separation.
AB  - Unprecedented in situ formation of artificial moth-eye structure is demonstrated
      by spontaneous nano-phase separation of a silica-based system on substrate. The
      moth-eye thin film with a homogenously distributed nipples array shows broadband
      antireflection functionalities. The mechanism of nano-phase separation is
      unveiled as spinodal decomposition by chemical freezing method and thermodynamic
      analysis. The current method may provide a new avenue to ready fabrication of
      patterned nanostructures toward a variety of applications.

PMID- 29348600
TI  - Chinese olive extract ameliorates hepatic lipid accumulation in vitro and in vivo
      by regulating lipid metabolism.
AB  - Chinese olive contains plenty of polyphenols, which possess a wide range of
      biological actions. In this study, we aimed to investigate the role of the ethyl
      acetate fraction of Chinese olive fruit extract (CO-EtOAc) in the modulation of
      lipid accumulation in vitro and in vivo. In cellular studies, CO-EtOAc attenuated
      oleic acid-induced lipid accumulation; we then elucidated the molecular
      mechanisms of CO-EtOAc in FL83B mouse hepatocytes. CO-EtOAc suppressed the mRNA
      levels of fatty acid transporter genes (CD36 and FABP) and lipogenesis genes
      (SREBP-1c, FAS, and ACC1), but upregulated genes that govern lipolysis (HSL) and
      lipid oxidation (PPARalpha, CPT-1, and ACOX). Moreover, CO-EtOAc increased the
      protein expression of phosphorylated AMPK, ACC1, CPT-1, and PPARalpha, but
      downregulated the expression of mature SREBP-1c and FAS. AMPK plays an essential
      role in CO-EtOAc-mediated amelioration of lipid accumulation. Furthermore, we
      confirmed that CO-EtOAc significantly inhibited body weight gain, epididymal
      adipose tissue weight, and hepatic lipid accumulation via regulation of the
      expression of fatty acid transporter, lipogenesis, and fatty acid oxidation genes
      and proteins in C57BL/6 mice fed a 60% high-fat diet. Therefore, Chinese olive
      fruits may have the potential to improve the metabolic abnormalities associated
      with fatty liver under high fat challenge.

PMID- 29348601
TI  - Exclusion from spheroid formation identifies loss of essential cell-cell adhesion
      molecules in colon cancer cells.
AB  - Many cell lines derived from solid cancers can form spheroids, which recapitulate
      tumor cell clusters and are more representative of the in vivo situation than 2D
      cultures. During spheroid formation, a small proportion of a variety of different
      colon cancer cell lines did not integrate into the sphere and lost cell-cell
      adhesion properties. An enrichment protocol was developed to augment the
      proportion of these cells to 100% purity. The basis for the separation of
      spheroids from non-spheroid forming (NSF) cells is simple gravity-sedimentation.
      This protocol gives rise to sub-populations of colon cancer cells with stable
      loss of cell-cell adhesion. SW620 cells lacked E-cadherin, DLD-1 cells lost alpha
      catenin and HCT116 cells lacked P-cadherin in the NSF state. Knockdown of these
      molecules in the corresponding spheroid-forming cells demonstrated that loss of
      the respective proteins were indeed responsible for the NSF phenotypes. Loss of
      the spheroid forming phenotype was associated with increased migration and
      invasion properties in all cell lines tested. Hence, we identified critical
      molecules involved in spheroid formation in different cancer cell lines. We
      present here a simple, powerful and broadly applicable method to generate new
      sublines of tumor cell lines to study loss of cell-cell adhesion in cancer
      progression.

PMID- 29348602
TI  - The ten-year evolutionary trajectory of a highly recurrent paediatric high grade
      neuroepithelial tumour with MN1:BEND2 fusion.
AB  - Astroblastomas are rare brain tumours which predominate in children and young
      adults, and have a controversial claim as a distinct entity, with no established
      WHO grade. Reports suggest a better outcome than high grade gliomas, though they
      frequently recur. Recently, they have been described to overlap with a newly
      discovered group of tumours described as'high grade neuroepithelial tumour with
      MN1 alteration' (CNS HGNET-MN1), defined by global methylation patterns and
      strongly associated with gene fusions targeting MN1. We have studied a unique
      case of astroblastoma arising in a 6 year-old girl, with multiple recurrences
      over a period of 10 years, with the pathognomonic MN1:BEND2 fusion. Exome
      sequencing allowed for a phylogenetic reconstruction of tumour evolution, which
      when integrated with clinical, pathological and radiological data provide for a
      detailed understanding of disease progression, with initial treatment driving
      tumour dissemination along four distinct trajectories. Infiltration of distant
      sites was associated with a later genome doubling, whilst there was evidence of
      convergent evolution of different lesions acquiring distinct alterations
      targeting NF-kappaB. These data represent an unusual opportunity to understand
      the evolutionary history of a highly recurrent childhood brain tumour, and
      provide novel therapeutic targets for astroblastoma/CNS HGNET-MN1.

PMID- 29348603
TI  - Comprehensive list of SUMO targets in Caenorhabditis elegans and its implication
      for evolutionary conservation of SUMO signaling.
AB  - Post-translational modification by small ubiquitin-related modifier (SUMO) is a
      key regulator of cell physiology, modulating protein-protein and protein-DNA
      interactions. Recently, SUMO modifications were postulated to be involved in
      response to various stress stimuli. We aimed to identify the near complete set of
      proteins modified by SUMO and the dynamics of the modification in stress
      conditions in the higher eukaryote, Caenorhabditis elegans. We identified 874
      proteins modified by SUMO in the worm. We have analyzed the SUMO modification in
      stress conditions including heat shock, DNA damage, arsenite induced cellular
      stress, ER and osmotic stress. In all these conditions the global levels of
      SUMOylation was significantly increased. These results show the evolutionary
      conservation of SUMO modifications in reaction to stress. Our analysis showed
      that SUMO targets are highly conserved throughout species. By comparing the SUMO
      targets among species, we approximated the total number of proteins modified in a
      given proteome to be at least 15-20%. We developed a web server designed for
      convenient prediction of potential SUMO modification based on experimental
      evidences in other species.

PMID- 29348605
TI  - Co-selected mutations in VCP: a novel mechanism of resistance to VCP inhibitors.

PMID- 29348604
TI  - Cromolyn Reduces Levels of the Alzheimer's Disease-Associated Amyloid beta
      Protein by Promoting Microglial Phagocytosis.
AB  - Amyloid-beta protein (Abeta) deposition is a pathological hallmark of Alzheimer's
      disease (AD). Abeta deposition triggers both pro-neuroinflammatory microglial
      activation and neurofibrillary tangle formation. Cromolyn sodium is an asthma
      therapeutic agent previously shown to reduce Abeta levels in transgenic AD mouse
      brains after one-week of treatment. Here, we further explored these effects as
      well as the mechanism of action of cromolyn, alone, and in combination with
      ibuprofen in APPSwedish-expressing Tg2576 mice. Mice were treated for 3 months
      starting at 5 months of age, when the earliest stages of beta-amyloid deposition
      begin. Cromolyn, alone, or in combination with ibuprofen, almost completely
      abolished longer insoluble Abeta species, i.e. Abeta40 and Abeta42, but increased
      insoluble Abeta38 levels. In addition to its anti-aggregation effects on Abeta,
      cromolyn, alone, or plus ibuprofen, but not ibuprofen alone, increased microglial
      recruitment to, and phagocytosis of beta-amyloid deposits in AD mice. Cromolyn
      also promoted Abeta42 uptake in microglial cell-based assays. Collectively, our
      data reveal robust effects of cromolyn, alone, or in combination with ibuprofen,
      in reducing aggregation-prone Abeta levels and inducing a neuroprotective
      microglial activation state favoring Abeta phagocytosis versus a pro
      neuroinflammatory state. These findings support the use of cromolyn, alone, or
      with ibuprofen, as a potential AD therapeutic.

PMID- 29348606
TI  - AMP-activated protein kinase agonist N6-(3-hydroxyphenyl)adenosine protects
      against fulminant hepatitis by suppressing inflammation and apoptosis.
AB  - Both AMP-activated protein kinase (AMPK) agonist and inhibitor have been reported
      to protect against fulminant hepatitis, implying that AMPK may play a complicated
      role in the development of fulminant hepatitis. In this study, we exploited
      whether the novel AMPK agonist N6-(3-hydroxyphenyl)adenosine (named as M1)
      exerted protective effects on fulminant hepatitis and whether its beneficial
      effects were AMPK-dependent. Results showed that intraperitoneal injection of M1
      improved liver function, ameliorated liver injury and finally raised the survival
      rate in D-galactosamine/lipopolysaccharide (GalN/LPS)-treated mice. These
      beneficial effects of M1 may attribute to the suppression of pro-inflammatory
      cytokines production and the prevention of hepatocyte apoptosis. Furthermore, M1
      pretreatment mitigated LPS-stimulated TLR4 expression and NFkappaB activation in
      murine peritoneal macrophages and prevented actinomycin D (Act D)/tumor necrosis
      factor alpha (TNFalpha)-induced apoptosis by promoting protective autophagy in
      primary hepatocytes. Additionally, M1-induced AMPK activation was responsible
      both for its anti-inflammatory action in macrophages and for its anti-apoptotic
      action in hepatocytes. To our surprise, compared with the control
      AMPKalpha1lox/lox/AMPKalpha2lox/lox mice, liver-specific AMPKalpha1 knockout
      (AMPKalpha1LS-/-) mice were more sensitive to GalN/LPS administration but not
      AMPKalpha2LS-/-mice, and the beneficial effects of M1 on acute liver failure and
      the production of pro-inflammatory factors were dampened in AMPKalpha1LS-/- mice.
      Therefore, our study may prove that M1 could be a promising therapeutic agent for
      fulminant hepatitis, and targeting AMPK may be useful therapeutically in the
      control of LPS-induced hepatotoxicity.

PMID- 29348607
TI  - Evaluation of mitochondrial bioenergetics, dynamics, endoplasmic reticulum
      mitochondria crosstalk, and reactive oxygen species in fibroblasts from patients
      with complex I deficiency.
AB  - Mitochondrial complex I (CI) deficiency is the most frequent cause of oxidative
      phosphorylation (OXPHOS) disorders in humans. In order to benchmark the effects
      of CI deficiency on mitochondrial bioenergetics and dynamics, respiratory chain
      (RC) and endoplasmic reticulum (ER)-mitochondria communication, and superoxide
      production, fibroblasts from patients with mutations in the ND6, NDUFV1 or ACAD9
      genes were analyzed. Fatty acid metabolism, basal and maximal respiration,
      mitochondrial membrane potential, and ATP levels were decreased. Changes in
      proteins involved in mitochondrial dynamics were detected in various combinations
      in each cell line, while variable changes in RC components were observed. ACAD9
      deficient cells exhibited an increase in RC complex subunits and DDIT3, an ER
      stress marker. The level of proteins involved in ER-mitochondria communication
      was decreased in ND6 and ACAD9 deficient cells. |DeltaPsi| and cell viability
      were further decreased in all cell lines. These findings suggest that disruption
      of mitochondrial bioenergetics and dynamics, ER-mitochondria crosstalk, and
      increased superoxide contribute to the pathophysiology in patients with ACAD9
      deficiency. Furthermore, treatment of ACAD9 deficient cells with JP4-039, a novel
      mitochondria-targeted reactive oxygen species, electron and radical scavenger,
      decreased superoxide level and increased basal and maximal respiratory rate,
      identifying a potential therapeutic intervention opportunity in CI deficiency.

PMID- 29348608
TI  - Phytase overexpression in Arabidopsis improves plant growth under osmotic stress
      and in combination with phosphate deficiency.
AB  - Engineering osmotolerant plants is a challenge for modern agriculture. An
      interaction between osmotic stress response and phosphate homeostasis has been
      reported in plants, but the identity of molecules involved in this interaction
      remains unknown. In this study we assessed the role of phytic acid (PA) in
      response to osmotic stress and/or phosphate deficiency in Arabidopsis thaliana.
      For this purpose, we used Arabidopsis lines (L7 and L9) expressing a bacterial
      beta-propeller phytase PHY-US417, and a mutant in inositol polyphosphate kinase 1
      gene (ipk1-1), which were characterized by low PA content, 40% (L7 and L9) and
      83% (ipk1-1) of the wild-type (WT) plants level. We show that the PHY
      overexpressor lines have higher osmotolerance and lower sensitivity to abscisic
      acid than ipk1-1 and WT. Furthermore, PHY-overexpressors showed an increase by
      more than 50% in foliar ascorbic acid levels and antioxidant enzyme activities
      compared to ipk1-1 and WT plants. Finally, PHY-overexpressors are more tolerant
      to combined mannitol stresses and phosphate deficiency than WT plants. Overall,
      our results demonstrate that the modulation of PA improves plant growth under
      osmotic stress, likely via stimulation of enzymatic and non-enzymatic antioxidant
      systems, and that beside its regulatory role in phosphate homeostasis, PA may be
      also involved in fine tuning osmotic stress response in plants.

PMID- 29348609
TI  - Effects of vitamin D supplementation on inflammatory markers in heart failure: a
      systematic review and meta-analysis of randomized controlled trials.
AB  - Vitamin D is reported to have anti-inflammatory properties; however the effects
      of vitamin D supplementation on inflammation in patients with heart failure (HF)
      have not been established. We performed a systematic review and meta-analysis
      examining effects of vitamin D supplementation on inflammatory markers in
      patients with HF. MEDLINE, CINAHL, EMBASE, All EBM, and Clinical Trials
      registries were systematically searched for RCTs from inception to 25 January
      2017. Two independent reviewers screened all full text articles (no date or
      language limits) for RCTs reporting effects of vitamin D supplementation (any
      form, route, duration, and co-supplementation) compared with placebo or usual
      care on inflammatory markers in patients with heart failure. Two reviewers
      assessed risk of bias and quality using the grading of recommendations,
      assessment, development, and evaluation approach. Seven studies met inclusion
      criteria and six had data available for pooling (n = 1012). In meta-analyses,
      vitamin D-supplemented groups had lower concentrations of tumor necrosis factor
      alpha (TNF-alpha) at follow-up compared with controls (n = 380; p = 0.04). There
      were no differences in C-reactive protein (n = 231), interleukin (IL)-10 (n =
      247) or IL-6 (n = 154) between vitamin D and control groups (all p > 0.05). Our
      findings suggest that vitamin D supplementation may have specific, but modest
      effects on inflammatory markers in HF.

PMID- 29348610
TI  - The histone methyltransferase DOT1L inhibits osteoclastogenesis and protects
      against osteoporosis.
AB  - Osteoclasts are absorptive cells that play a critical role in homeostatic bone
      remodeling and pathological bone resorption. Emerging evidence suggests an
      important role of epigenetic regulation in osteoclastogenesis. In this study, we
      investigated the role of DOT1L, which regulates gene expression epigenetically by
      histone H3K79 methylation (H3K79me), during osteoclast formation. Using RANKL
      induced RAW264.7 macrophage cells as an osteoclast differentiation model, we
      found that DOT1L and H3K79me2 levels were upregulated during osteoclast
      differentiation. Small molecule inhibitor- (EPZ5676 or EPZ004777) or short
      hairpin RNA-mediated reduction in DOT1L expression promoted osteoclast
      differentiation and resorption. In addition, DOT1L inhibition increased
      osteoclast surface area and accelerated bone-mass reduction in a mouse
      ovariectomy (OVX) model of osteoporosis without alter osteoblast differentiation.
      DOT1L inhibition increase reactive oxygen species (ROS) generation and autophagy
      activity, and cell migration in pre-osteoclasts. Moreover, it strengthened
      expression of osteoclast fusion and resorption-related protein CD9 and MMP9 in
      osteoclasts derived from RAW264.7. Our findings support a new mechanism of DOT1L
      regulated, H3K79me2-mediated, epigenetic regulation of osteoclast
      differentiation, implicating DOT1L as a new therapeutic target for osteoclast
      dysregulation-induced disease.

PMID- 29348611
TI  - Prediction is Production: The missing link between language production and
      comprehension.
AB  - Language comprehension often involves the generation of predictions. It has been
      hypothesized that such prediction-for-comprehension entails actual language
      production. Recent studies provided evidence that the production system is
      recruited during language comprehension, but the link between production and
      prediction during comprehension remains hypothetical. Here, we tested this
      hypothesis by comparing prediction during sentence comprehension (primary task)
      in participants having the production system either available or not (non-verbal
      versus verbal secondary task). In the primary task, sentences containing an
      expected or unexpected target noun-phrase were presented during
      electroencephalography recording. Prediction, measured as the magnitude of the
      N400 effect elicited by the article (expected versus unexpected), was hindered
      only when the production system was taxed during sentence context reading. The
      present study provides the first direct evidence that the availability of the
      speech production system is necessary for generating lexical prediction during
      sentence comprehension. Furthermore, these important results provide an
      explanation for the recruitment of language production during comprehension.

PMID- 29348613
TI  - Solar system expansion and strong equivalence principle as seen by the NASA
      MESSENGER mission.
AB  - The NASA MESSENGER mission explored the innermost planet of the solar system and
      obtained a rich data set of range measurements for the determination of Mercury's
      ephemeris. Here we use these precise data collected over 7 years to estimate
      parameters related to general relativity and the evolution of the Sun. These
      results confirm the validity of the strong equivalence principle with a
      significantly refined uncertainty of the Nordtvedt parameter eta = (-6.6 +/- 7.2)
      * 10-5. By assuming a metric theory of gravitation, we retrieved the post
      Newtonian parameter beta = 1 + (-1.6 +/- 1.8) * 10-5 and the Sun's gravitational
      oblateness, [Formula: see text] = (2.246 +/- 0.022) * 10-7. Finally, we obtain an
      estimate of the time variation of the Sun gravitational parameter, [Formula: see
      text] = (-6.13 +/- 1.47) * 10-14, which is consistent with the expected solar
      mass loss due to the solar wind and interior processes. This measurement allows
      us to constrain [Formula: see text] to be <4 * 10-14 per year.

PMID- 29348612
TI  - GWAS in childhood acute lymphoblastic leukemia reveals novel genetic associations
      at chromosomes 17q12 and 8q24.21.
AB  - Childhood acute lymphoblastic leukemia (ALL) (age 0-14 years) is 20% more common
      in Latino Americans than non-Latino whites. We conduct a genome-wide association
      study in a large sample of 3263 Californian children with ALL (including 1949 of
      Latino heritage) and 3506 controls matched on month and year of birth, sex, and
      ethnicity, and an additional 12,471 controls from the Kaiser Resource for Genetic
      Epidemiology Research on Aging Cohort. Replication of the strongest genetic
      associations is performed in two independent datasets from the Children's
      Oncology Group and the California Childhood Leukemia Study. Here we identify new
      risk loci on 17q12 near IKZF3/ZPBP2/GSDMB/ORMDL3, a locus encompassing a
      transcription factor important for lymphocyte development (IKZF3), and at an 8q24
      region known for structural contacts with the MYC oncogene. These new risk loci
      may impact gene expression via local (four 17q12 genes) or long-range (8q24)
      interactions, affecting function of well-characterized hematopoietic and growth
      regulation pathways.

PMID- 29348614
TI  - Noise-induced bistability in the fate of cancer phenotypic quasispecies: a bit
      strings approach.
AB  - Tumor cell populations are highly heterogeneous. Such heterogeneity, both at
      genotypic and phenotypic levels, is a key feature during tumorigenesis. How to
      investigate the impact of this heterogeneity in the dynamics of tumors cells
      becomes an important issue. Here we explore a stochastic model describing the
      competition dynamics between a pool of heterogeneous cancer cells with distinct
      phenotypes and healthy cells. This model is used to explore the role of
      demographic fluctuations on the transitions involving tumor clearance. Our
      results show that for large population sizes, when demographic fluctuations are
      negligible, there exists a sharp transition responsible for tumor cells
      extinction at increasing tumor cells' mutation rates. This result is consistent
      with a mean field model developed for the same system. The mean field model
      reveals only monostability scenarios, in which either the dominance of the tumor
      cells or the dominance of the healthy cells is found. Interestingly, the
      stochastic model shows that for small population sizes the monostability behavior
      disappears, involving the presence of noise-induced bistability. The impact of
      the initial populations of cells in the fate of the cell populations is
      investigated, as well as the transient times towards the healthy and the cancer
      states.

PMID- 29348615
TI  - Nucleation and Ostwald Growth of Particles in Fe-O-Al-Ca Melt.
AB  - Tremendous focus has been put on the control of particle size distribution which
      effects the grain structure and mechanical properties of resulting metallic
      materials, and thus nucleation and growth of particles in solution should be
      clarified. This study uses classical nucleation theory and Ostwald ripening
      theory to probe the relationship between the compositions of Fe-O-Al-Ca melts and
      the behavior of particles under the condition of no external stirring. Our
      experimental data suggest that decreasing the initial Ca addition and Al addition
      is conductive to the increase of nucleation rate for calcium aluminate particles,
      which exhibits a same change trend with that predicted from classical nucleation
      theory. Based on the experimental evidence for particles size distribution in
      three-dimensional, we demonstrate that Ostwald ripening is the predominate
      mechanism on the coarsening of particles in Fe-O-Al-Ca melt at early stage of
      deoxidation under the condition of no external stirring but not at later stage.

PMID- 29348616
TI  - Fast and effective mitochondrial delivery of omega-Rhodamine-B-polysulfobetaine
      PEG copolymers.
AB  - Mitochondrial targeting and entry, two crucial steps in fighting severe diseases
      resulting from mitochondria dysfunction, pose important challenges in current
      nanomedicine. Cell-penetrating peptides or targeting groups, such as Rhodamine-B
      (Rho), are known to localize in mitochondria, but little is known on how to
      enhance their effectiveness through structural properties of polymeric carriers.
      To address this issue, we prepared 8 copolymers of 3
      dimethyl(methacryloyloxyethyl)ammonium propane sulfonate and poly(ethyleneglycol)
      methacrylate, p(DMAPS-ran-PEGMA) (molecular weight, 18.0 < M n  < 74.0 kg/mol)
      with two different endgroups. We labeled them with Rho groups attached along the
      chain or on one of the two endgroups (alpha or omega). From studies by flow
      cytometry and confocal fluorescence microscopy of the copolymers internalization
      in HeLa cells in the absence and presence of pharmacological inhibitors, we
      established that the polymers cross the cell membrane foremost by translocation
      and also by endocytosis, primarily clathrin-dependent endocytosis. The most
      effective mitochondrial entry was achieved by copolymers of M n  < 30.0 kg/mol,
      lightly grafted with PEG chains (< 5 mol %) labeled with Rho in the omega
      position. Our findings may be generalized to the uptake and mitochondrial
      targeting of prodrugs and imaging agents with a similar polymeric scaffold.

PMID- 29348617
TI  - Neuronal lysosomal dysfunction releases exosomes harboring APP C-terminal
      fragments and unique lipid signatures.
AB  - Defects in endolysosomal and autophagic functions are increasingly viewed as key
      pathological features of neurodegenerative disorders. A master regulator of these
      functions is phosphatidylinositol-3-phosphate (PI3P), a phospholipid synthesized
      primarily by class III PI 3-kinase Vps34. Here we report that disruption of
      neuronal Vps34 function in vitro and in vivo impairs autophagy, lysosomal
      degradation as well as lipid metabolism, causing endolysosomal membrane damage.
      PI3P deficiency also promotes secretion of unique exosomes enriched for
      undigested lysosomal substrates, including amyloid precursor protein C-terminal
      fragments (APP-CTFs), specific sphingolipids, and the phospholipid
      bis(monoacylglycero)phosphate (BMP), which normally resides in the internal
      vesicles of endolysosomes. Secretion of these exosomes requires neutral
      sphingomyelinase 2 and sphingolipid synthesis. Our results reveal a homeostatic
      response counteracting lysosomal dysfunction via secretion of atypical exosomes
      eliminating lysosomal waste and define exosomal APP-CTFs and BMP as candidate
      biomarkers for endolysosomal dysfunction associated with neurodegenerative
      disorders.

PMID- 29348618
TI  - Epigallocatechin gallate (EGCG) reduces the intensity of pancreatic amyloid
      fibrils in human islet amyloid polypeptide (hIAPP) transgenic mice.
AB  - The formation of amyloid fibrils by human islet amyloid polypeptide protein
      (hIAPP) has been implicated in pancreas dysfunction and diabetes. However,
      efficient treatment options to reduce amyloid fibrils in vivo are still lacking.
      Therefore, we tested the effect of epigallocatechin gallate (EGCG) on fibril
      formation in vitro and in vivo. To determine the binding of hIAPP and EGCG, in
      vitro interaction studies were performed. To inhibit amyloid plaque formation in
      vivo, homozygous (tg/tg), hemizygous (wt/tg), and control mice (wt/wt) were
      treated with EGCG. EGCG bound to hIAPP in vitro and induced formation of
      amorphous aggregates instead of amyloid fibrils. Amyloid fibrils were detected in
      the pancreatic islets of tg/tg mice, which was associated with disrupted islet
      structure and diabetes. Although pancreatic amyloid fibrils could be detected in
      wt/tg mice, these animals were non-diabetic. EGCG application decreased amyloid
      fibril intensity in wt/tg mice, however it was ineffective in tg/tg animals. Our
      data indicate that EGCG inhibits amyloid fibril formation in vitro and reduces
      fibril intensity in non-diabetic wt/tg mice. These results demonstrate a possible
      in vivo effectiveness of EGCG on amyloid formation and suggest an early
      therapeutical application.

PMID- 29348619
TI  - Cytokine-mediated changes in K+ channel activity promotes an adaptive Ca2+
      response that sustains beta-cell insulin secretion during inflammation.
AB  - Cytokines present during low-grade inflammation contribute to beta-cell
      dysfunction and diabetes. Cytokine signaling disrupts beta-cell glucose
      stimulated Ca2+ influx (GSCI) and endoplasmic reticulum (ER) Ca2+ ([Ca2+]ER)
      handling, leading to diminished glucose-stimulated insulin secretion (GSIS).
      However, cytokine-mediated changes in ion channel activity that alter beta-cell
      Ca2+ handling remain unknown. Here we investigated the role of K+ currents in
      cytokine-mediated beta-cell dysfunction. Kslow currents, which control the
      termination of intracellular Ca2+ ([Ca2+]i) oscillations, were reduced following
      cytokine exposure. As a consequence, [Ca2+]i and electrical oscillations were
      accelerated. Cytokine exposure also increased basal islet [Ca2+]i and decreased
      GSCI. The effect of cytokines on TALK-1 K+ currents were also examined as TALK-1
      mediates Kslow by facilitating [Ca2+]ER release. Cytokine exposure decreased
      KCNK16 transcript abundance and associated TALK-1 protein expression, increasing
      [Ca2+]ER storage while maintaining 2nd phase GSCI and GSIS. This adaptive Ca2+
      response was absent in TALK-1 KO islets, which exhibited decreased 2nd phase GSCI
      and diminished GSIS. These findings suggest that Kslow and TALK-1 currents play
      important roles in altered beta-cell Ca2+ handling and electrical activity during
      low-grade inflammation. These results also reveal that a cytokine-mediated
      reduction in TALK-1 serves an acute protective role in beta-cells by facilitating
      increased Ca2+ content to maintain GSIS.

PMID- 29348620
TI  - A vacuolar sorting receptor-independent sorting mechanism for storage vacuoles in
      soybean seeds.
AB  - The seed storage proteins of soybean (Glycine max) are composed mainly of
      glycinin (11S globulin) and beta-conglycinin (7S globulin). The subunits of
      glycinin (A1aB1b, A1bB2, A2B1a, A3B4, and A5A4B3) are synthesized as a single
      polypeptide precursor. These precursors are assembled into trimers with a random
      combination of subunits in the endoplasmic reticulum, and are sorted to the
      protein storage vacuoles. Proteins destined for transport to protein storage
      vacuoles possess a vacuolar sorting determinant, and in this regard, the A1aB1b
      subunit contains a C-terminal peptide that is sufficient for its sorting to
      protein storage vacuoles. The A3B4 subunit, however, lacks a corresponding C
      terminal sorting determinant. In this study, we found that, unlike the A1aB1b
      subunit, the A3B4 subunit does not bind to previously reported vacuolar sorting
      receptors. Despite this difference, we observed that the A3B4 subunit is sorted
      to protein storage vacuoles in a transgenic soybean line expressing the A3B4
      subunit of glycinin. These results indicate that a protein storage vacuolar
      sorting mechanism that functions independently of the known vacuolar sorting
      receptors in seeds might be present in soybean seeds.

PMID- 29348621
TI  - Dynamic cellular maps of molecular species: Application to drug-target
      interactions.
AB  - The design of living cell studies aimed at deciphering the mechanism of action of
      drugs targeting proteins with multiple functions, expressed in a wide range of
      concentrations and cellular locations, is a real challenge. We recently showed
      that the antitumor drug plitidepsin (APL) localizes sufficiently close to the
      elongation factor eEF1A2 so as to suggest the formation of drug-protein complexes
      in living cells. Here we present an extension of our previous micro-spectroscopy
      study, that combines Generalized Polarization (GP) images, with the phasor
      approach and fluorescence lifetime imaging microscopy (FLIM), using a 7
      aminocoumarin drug analog (APL*) as fluorescence tracer. Using the proposed
      methodology, we were able to follow in real time the formation and relative
      distribution of two sets of APL-target complexes in live cells, revealing two
      distinct patterns of behavior for HeLa-wt and APL resistant HeLa-APL-R cells. The
      information obtained may complement and facilitate the design of new experiments
      and the global interpretation of the results obtained with other biochemical and
      cell biology methods, as well as possibly opening new avenues of study to
      decipher the mechanism of action of new drugs.

PMID- 29348622
TI  - A novel method of utilizing skinfolds and bioimpedance for determining body fat
      percentage via a field-based three-compartment model.
AB  - BACKGROUND/OBJECTIVES: The purpose was to determine if skinfolds (SF) and
      bioelectrical impedance analysis (BIA) could provide accurate estimates of body
      volume (BV) and total body water (TBW), respectively, for use in a 3-compartment
      (3-C) model to estimate percent body fat (BF%) when compared to laboratory
      derived measures. SUBJECTS/METHODS: A sample of sixty-four men (age = 22.9 +/-
      5.4 years) and 59 women (age = 21.6 +/- 4.3 years) participated in the study.
      Laboratory 3-C (3CLAB) model BF% was determined with underwater weighing for body
      volume (BV) and bioimpedance spectroscopy for total body water (TBW). The 3-C
      field (3CFIELD) estimates of BF% included BV from the 7-site SF technique and TBW
      from hand-to-foot BIA. RESULTS: A significant difference in BF% (p < 0.01) was
      found between the 3CLAB and 3CFIELD in the entire sample and within the men, but
      the effect sizes (ES) were small (0.09 and 0.17, respectively). The difference
      between means was not significant in the women (ES = 0.05, p = 0.332). Compared
      to the 3CLAB, the total error (TE) ranged 2.2-2.4% for 3CFIELD, 5.7-5.8% for SF,
      and 4.0-4.6% for BIA. CONCLUSIONS: The findings suggest that BV and TBW derived
      from SF and BIA, respectively, can be used in a 3CFIELD model to increase the
      accuracy of BF% estimates over SF and BIA alone.

PMID- 29348623
TI  - Fetal vitamin D concentration and growth, adiposity and neurodevelopment during
      infancy.
AB  - BACKGROUND/OBJECTIVES: To determine the association between cord blood 25
      hydroxyvitamin D (25(OH)D) concentration with growth, adiposity and
      neurodevelopment during infancy. SUBJECTS/METHODS: Serum 25(OH)D was measured in
      cord blood by the liquid chromatography tandem mass spectrometry (LC-MS/MS) from
      the Shanghai's "Allergy and Obesity Cohort study" (n = 1244). Weight, length,
      head circumference, and body mass index (BMI) z-scores for age were calculated
      based on World Health Organization Standard (at 6 months, 1 years, and 2 years).
      Neurodevelopment was measured at 2 years using Ages and Stages Questionnaire.
      Generalized estimating equation and multivariable logistic regression model were
      exploited to examine associations between fetal 25(OH)D concentration and
      offspring outcomes. RESULTS: The median of the 25(OH)D concentration in cord
      blood was 22.4 ng/ml (interquartile range, 27.3-8.6). Infants born in winter had
      lower 25(OH)D concentration. 25(OH)D deficiency was not associated with weight z
      score (mean difference, 0.07; 95% confidence internal (CI), -0.09 to 0.23),
      length z-score (mean difference, 0.01; 95% CI, -0.19 to 0.21), head circumference
      z-score (mean difference, -0.06; 95% CI, -0.27 to 0.15) and BMI z-score (mean
      difference, 0.09; 95% CI, -0.07 to 0.25) or neurodevelopment during infancy,
      adjusting for sex, socio-economic position, pre-pregnancy maternal BMI, and
      maternal and neonatal characteristics. The associations did not vary by gender. A
      sensitivity analysis of available case analysis showed virtually the same
      results. CONCLUSIONS: Fetal vitamin D concentration was not associated with
      growth, adiposity or neurodevelopment during infancy. The role of vitamin D
      concentration and its mechanistic pathway in the early origins of adiposity needs
      to be clarified.

PMID- 29348624
TI  - Soy food and isoflavone intake reduces the risk of cognitive impairment in
      elderly Japanese women.
AB  - Data were derived from the National Institute for Longevity Sciences-Longitudinal
      Study of Aging. Subjects comprised 403 men and 373 women aged 60-81 years at
      baseline who participated in the follow-up study at least once. Bean, soy product
      and soy isoflavone intake was assessed using a 3-day dietary record at baseline.
      Cognitive function was assessed by the Mini-Mental State Examination (MMSE). MMSE
      scores of <=23 were used to define cognitive impairment. The relationship between
      bean, soy product and soy isoflavone intake and cognitive impairment was assessed
      using a generalized estimating equation. Multivariate-adjusted odds ratios (95%
      confidence intervals) for cognitive impairment with a 1 s.d. increase in total
      bean, total soybean and total soy isoflavone intakes were 0.48 (0.28-0.81; p =
      0.006), 0.51 (0.32-0.83; p = 0.007), and 0.55 (0.32-0.93; p = 0.026),
      respectively, in women. Total soybean and soy isoflavone intake might decrease
      the risk of cognitive impairment in elderly Japanese women.

PMID- 29348625
TI  - Universal type/subtype-specific antibodies for quantitative analyses of
      neuraminidase in trivalent influenza vaccines.
AB  - Both influenza viral hemagglutinin and neuraminidase can induce protective immune
      responses in humans. Although the viral hemagglutinin antigens have been
      quantified in influenza vaccines, the amounts of neuraminidase remain
      undetermined. Using comprehensive bioinformatics analyses of all neuraminidase
      sequences, we identified highly conserved and subtype-specific peptide epitopes
      within each of N1, N2 and type B neuraminidase groups. Mono-specific antibodies
      generated against these peptides bound to their respective subtype/type only
      while demonstrating remarkable specificity against the viral neuraminidase
      sequences without any cross-reactivity with allantoic and cellular proteins.
      Moreover, the subtype/type-specific antibodies were found not to interfere with
      one another when a mixture of vaccine samples was analysed. Importantly,
      immunoassay based on these antibodies can quantitatively determine neuraminidase
      in commercial trivalent vaccine samples. Analyses of vaccines from eight
      manufacturers using the same vaccine seeds revealed significant differences in
      neuraminidase levels. Specifically, while the ratio between neuraminidase and
      hemagglutinin in some products are found to be close 1/5, other products have a
      ratio of approximately 1/100, a level which is far below the theoretical ratio
      between neuraminidase and hemagglutinin in a virus. The antibody-based assays
      reported here could be of great value for better quality control of both
      monovalent and trivalent vaccines.

PMID- 29348626
TI  - Arabidopsis serine/threonine/tyrosine protein kinase phosphorylates oil body
      proteins that regulate oil content in the seeds.
AB  - Protein phosphorylation is an important post-translational modification that can
      regulate the protein function. The current knowledge on the phosphorylation
      status of plant oil body (OB) proteins is inadequate. This present study
      identifies the distinct physiological substrates of Arabidopsis
      serine/threonine/tyrosine protein kinase (STYK) and its role in seed oil
      accumulation; the role of Arabidopsis OLE1, a major seed OB protein has also been
      elucidated. In vitro kinase assay followed by mass spectrometry identifies
      residue that are phosphorylated by STYK. Further, co-expression of OLE1 and STYK
      in yeast cells increases the cellular lipid levels and reduces the total lipid
      when OLE1 was replaced with OLE1T166A. Moreover, in vivo experiments with OB
      isolated from wild-type and styk knock-out lines show the ability of STYK to
      phosphorylate distinct OB proteins. OLE1T166A mutant and Arabidopsis styk mutant
      demonstrate the significant reduction of its substrate phosphorylation. styk
      mutant line significantly reduces the amount of total seed oil as compared to
      wild-type seeds. Together, our results provide the evidences that Arabidopsis
      At2G24360 (STYK) is phosphorylating oil body proteins and the phosphorylation
      regulates the oil content in Arabidopsis seeds.

PMID- 29348627
TI  - Chikungunya virus nsP1 interacts directly with nsP2 and modulates its ATPase
      activity.
AB  - Chikungunya virus (CHIKV) is a mosquito-borne virus, which has created an
      alarming threat in the world due to unavailability of vaccine and antiviral
      compounds. The CHIKV nsP2 contains ATPase, RTPase, helicase and protease
      activities, whereas, nsP1 is a viral capping enzyme. In alphaviruses, the four
      non-structural proteins form the replication complex in the cytoplasm and this
      study characterizes the interaction between CHIKV nsP1 and nsP2. It was observed
      that, both the proteins co-localize in the cytoplasm and interact in the CHIKV
      infected cells by confocal microscopy and immunoprecipitation assay. Further, it
      was demonstrated through mutational analysis that, the amino acids 1-95 of nsP2
      and 170-288 of nsP1 are responsible for their direct interaction. Additionally,
      it was noticed that, the ATPase activity of nsP2 is enhanced in the presence of
      nsP1, indicating the functional significance of this interaction. In silico
      analysis showed close (<=1.7 A) polar interaction (hydrogen bond) between Glu4,
      Arg7, 96, 225 of nsP2 with Lys256, 206, Val367 and Phe312 of nsP1 respectively.
      Hence, this investigation provides molecular characterization of CHIKV nsP1-nsP2
      interaction which might be a useful target for rational designing of antiviral
      drugs.

PMID- 29348628
TI  - FEZF1-AS1/miR-107/ZNF312B axis facilitates progression and Warburg effect in
      pancreatic ductal adenocarcinoma.
AB  - Long non-coding RNAs (lncRNAs) play a pivotal role in pathological processes.
      However, little information has been published regarding the underlying functions
      and mechanisms of lncRNAs in pancreatic ductal adenocarcinoma (PDAC). A novel
      lncRNA FEZF1-AS1 and its sense-cognate gene ZNF312B were found to be highly
      expressed in human PDAC tissues and cell lines, which is associated with disease
      progression and predicts clinical outcome in PDAC patients. Of note,
      bioinformatics analysis, luciferase assays and RNA immunoprecipitation assays
      indicated that FEZF1-AS1 may act as an endogenous sponge by competing for miR
      107, thereby modulating the derepression of ZNF312B. Downregulation of FEZF1-AS1
      or ZNF312B significantly inhibited proliferation, colony formation, migration,
      and invasion of PDAC cells in vitro, whereas the miR-107 inhibitor abrogated the
      effect of dow-regulation of FEZF1-AS1 or ZNF312B in reducing oncogenic capacities
      of PDAC cells. In addition, FEZF1-AS1/miR-107/ZNF312B axis-induced promotion of
      PDAC cells proliferation appeared to be mediated by modulation of the apoptosis
      and the G1-S checkpoint. Furthermore, downregulation of FEZF1-AS1 repressed tumor
      growth in mouse xenograft models. In particular, our results highlight the
      contribution of FEZF1-AS1/miR-107/ZNF312B axis to Warburg effect maintenance of
      PDAC cells. Collectively, our findings demonstrate that the FEZF1-AS1/miR
      107/ZNF312B axis regulatory network might provide a potential new therapeutic
      strategy for PDAC.

PMID- 29348629
TI  - The suppressive role of calcium sensing receptor in endometrial cancer.
AB  - Studies have shown that calcium sensing receptor (CaSR) is involved in the
      progressions of several human cancers. However, the role of CaSR in endometrial
      cancer remains unknown. This study provides a preliminary analysis of the CaSR
      effect on endometrial cancer development. Ectopic CaSR expression by lentiviral
      transfection (CaSR-OV) in Ishikawa cells significantly increased intracellular
      calcium ([Ca2+]i) levels and cell apoptosis. E-cadherin and beta-catenin
      expression and complex formation at the membrane were increased in CaSR-OV
      Ishikawa cells relative to control Ishikawa cells (vector). Furthermore, CaSR-OV
      Ishikawa cells showed a reduced invasive potential, which was attributed to E
      cadherin/beta-catenin complex formation. Moreover, a reduction in CaSR expression
      in endometrial cancer relative to normal specimens was evident by
      immunohistochemistry and was positively associated with E-cadherin, but not beta
      catenin, expression. Furthermore, VEGFR3 was significantly down-regulated in CaSR
      OV Ishikawa cells. Additionally, an immunohistochemical analysis showed that
      VEGFR3 was significantly increased in endometrial cancer compared with the normal
      endometrium and was inversely correlated with CaSR expression. However, the CaSR
      knockdown produced the opposite effects. These findings suggest an inhibitory
      role for CaSR in endometrial cancer. Therefore, reduced CaSR expression may be a
      suitable explanation and valuable predictor for endometrial cancer progression.

PMID- 29348630
TI  - Expression of inflammasome proteins and inflammasome activation occurs in human,
      but not in murine keratinocytes.
AB  - Inflammasomes are multimeric protein complexes that assemble upon sensing of a
      variety of stress factors. Their formation results in caspase-1-mediated
      activation and secretion of the pro-inflammatory cytokines pro-interleukin(IL)
      1beta and -18, which induce an inflammatory response. Inflammation is supported
      by a lytic form of cell death, termed pyroptosis. Innate immune cells, such as
      macrophages or dendritic cells, express and activate inflammasomes. However, it
      has also been demonstrated that human primary keratinocytes activate different
      types of inflammasomes in vitro, for example, upon UVB irradiation or viral
      infection. Keratinocytes are the main cell type of the epidermis, the outermost
      layer of the body, and form a protective barrier consisting of a stratified multi
      layered epithelium. In human, gain-of-function mutations of the NLRP1 gene cause
      syndromes mediated by inflammasome activation in keratinocytes that are
      characterised by skin inflammation and skin cancer susceptibility. Here we
      demonstrate that murine keratinocytes do not activate inflammasomes in response
      to stimuli, which induce IL-1beta and -18 secretion by human keratinocytes.
      Whereas murine keratinocytes produced caspase-1 and proIL-18, expression of the
      inflammasome proteins Nlrp1, Nlrp3, Aim2, Asc, and proIL-1beta was, compared to
      human keratinocytes or murine dendritic cells, very low or even undetectable.
      Priming of murine keratinocytes with cytokines commonly used for induction of
      proIL-1beta and inflammasome protein expression did not rescue inflammasome
      activation. Nevertheless, UVB-induced inflammation and neutrophil recruitment in
      murine skin was dependent on IL-1beta and caspase-1. However, also under these
      conditions, we did not detect expression of proIL-1beta by keratinocytes in
      murine skin, but by immune cells. These results demonstrate a higher
      immunological competence of human compared to murine keratinocytes, which is
      reflected by stress-induced IL-1beta secretion that is mediated by inflammasomes.
      Therefore, keratinocytes in human skin can exert immune functions, which are
      carried out by professional immune cells in murine skin.

PMID- 29348631
TI  - Dynamic all-optical drug screening on cardiac voltage-gated ion channels.
AB  - Voltage-gated ion channels (VGCs) are prime targets for the pharmaceutical
      industry, but drug profiling on VGCs is challenging, since drug interactions are
      confined to specific conformational channel states mediated by changes in
      transmembrane potential. Here we combined various optogenetic tools to develop
      dynamic, high-throughput drug profiling assays with defined light-step protocols
      to interrogate VGC states on a millisecond timescale. We show that such light
      induced electrophysiology (LiEp) yields high-quality pharmacological data with
      exceptional screening windows for drugs acting on the major cardiac VGCs,
      including hNav1.5, hKv1.5 and hERG. LiEp-based screening remained robust when
      using a variety of optogenetic actuators (ChR2, ChR2(H134R), CatCh, ChR2-EYFP
      betaArchT) and different types of organic (RH421, Di-4-ANBDQPQ, BeRST1) or
      genetic voltage sensors (QuasAr1). The tractability of LiEp allows a versatile
      and precise alternative to state-of-the-art VGC drug screening platforms such as
      automated electrophysiology or FLIPR readers.

PMID- 29348632
TI  - Climate Degradation and Extreme Icing Events Constrain Life in Cold-Adapted
      Mammals.
AB  - Despite the growth in knowledge about the effects of a warming Arctic on its cold
      adapted species, the mechanisms by which these changes affect animal populations
      remain poorly understood. Increasing temperatures, declining sea ice and altered
      wind and precipitation patterns all may affect the fitness and abundance of
      species through multiple direct and indirect pathways. Here we demonstrate
      previously unknown effects of rain-on-snow (ROS) events, winter precipitation,
      and ice tidal surges on the Arctic's largest land mammal. Using novel field data
      across seven years and three Alaskan and Russian sites, we show arrested skeletal
      growth in juvenile muskoxen resulting from unusually dry winter conditions and
      gestational ROS events, with the inhibitory effects on growth from ROS events
      lasting up to three years post-partum. Further, we describe the simultaneous
      entombment of 52 muskoxen in ice during a Chukchi Sea winter tsunami (ivuniq in
      Inupiat), and link rapid freezing to entrapment of Arctic whales and otters. Our
      results illustrate how once unusual, but increasingly frequent Arctic weather
      events affect some cold-adapted mammals, and suggest that an understanding of
      species responses to a changing Arctic can be enhanced by coalescing groundwork,
      rare events, and insights from local people.

PMID- 29348633
TI  - Contrasting patterns of prehistoric human diet and subsistence in northernmost
      Europe.
AB  - Current archaeological evidence indicates the transition from hunting-fishing
      gathering to agriculture in Northern Europe was a gradual process. This
      transition was especially complex in the prehistoric North Fennoscandian
      landscape where the high latitude posed a challenge to both domestic animal
      breeding and cereal cultivation. The conditions varied, the coastal dwellers had
      access to rich marine resources and enjoyed a milder climate due to the Gulf
      Stream, while those living in the inland Boreal forest zone faced longer and
      colder winters and less diversity in animal and plant resources. Thus, the
      coastal area provided more favourable conditions for early agriculture compared
      to those found inland. Interestingly, a cultural differentiation between these
      areas is archaeologically visible from the late 2nd millennium BC onwards. This
      is most clearly seen in regionally distinct pottery styles, offering unique
      opportunities to probe diet and subsistence through the organic residues
      preserved in ceramic vessels. Herein, we integrate the lipid biomarker, compound
      specific stable carbon isotopes (delta13C), and zooarchaeological evidence to
      reveal culturally distinct human diets and subsistence patterns. In northern
      Norway, some of the coastal people adopted dairying as part of their subsistence
      strategy, while the inhabitants of the interior, in common with northern Finland,
      continued their hunter-gatherer-fisher lifestyles.

PMID- 29348635
TI  - Publisher Correction: Spermine synthase deficiency causes lysosomal dysfunction
      and oxidative stress in models of Snyder-Robinson syndrome.
AB  - The originally published version of this Article contained errors in Figure 1. In
      panel c, the grey shading denoting evolutionary conservation and the arrowheads
      indicating amino acids affected in Snyder-Robinson syndrome were displaced
      relative to the sequence. These errors have now been corrected in both the PDF
      and HTML versions of the manuscript.

PMID- 29348634
TI  - A biosensor-based framework to measure latent proteostasis capacity.
AB  - The pool of quality control proteins (QC) that maintains protein-folding
      homeostasis (proteostasis) is dynamic but can become depleted in human disease. A
      challenge has been in quantitatively defining the depth of the QC pool. With a
      new biosensor, flow cytometry-based methods and mathematical modeling we measure
      the QC capacity to act as holdases and suppress biosensor aggregation. The
      biosensor system comprises a series of barnase kernels with differing folding
      stability that engage primarily with HSP70 and HSP90 family proteins. Conditions
      of proteostasis stimulation and stress alter QC holdase activity and aggregation
      rates. The method reveals the HSP70 chaperone cycle to be rate limited by HSP70
      holdase activity under normal conditions, but this is overcome by increasing
      levels of the BAG1 nucleotide exchange factor to HSPA1A or activation of the heat
      shock gene cluster by HSF1 overexpression. This scheme opens new paths for
      biosensors of disease and proteostasis systems.

PMID- 29348636
TI  - The gamma gap predicts 4-year all-cause mortality among nonagenarians and
      centenarians.
AB  - Recent studies have revealed the prognostic role of the gamma gap, the total
      serum proteins concentration minus the albumin concentration, for predicting all
      cause mortality among adults. This study aims to investigate the relationship
      between the gamma gap and all-cause mortality among nonagenarians and
      centenarians via a secondary data analysis of a prospective observational study.
      The analysis included 801 participants (260 men and 541 women, mean age: 93.7 +/-
      3.5 years), 46 of which were lost at the 4-year follow-up. The mean gamma gap was
      2.7 +/- 0.5 g/dl. After adjusting for relevant confounders, the gamma gap was
      significantly associated with 4-year all-cause mortality (hazard ratio [HR] per 1
      SD = 1.22, 95% confidential interval [CI]: 1.12-1.78). Using different cut-off
      points, the elevated gamma gap could be defined as >=2.9, 3.0, 3.1, or 3.2 g/dl.
      The relevant HRs and 95% CIs of the elevated gamma gap for predicting mortality
      were 1.27 (1.12-1.90), 1.29 (1.03-1.78), 1.21 (1.23-1.66), and 1.26 (1.09-1.69),
      respectively. In conclusion, the gamma gap is an independent prognostic factor
      for long-term mortality in nonagenarians and centenarians. A value greater than
      or equal to 3.1 g/dl may define an elevated gamma gap, but further studies are
      required.

PMID- 29348637
TI  - Plasmodium dihydrofolate reductase is a second enzyme target for the antimalarial
      action of triclosan.
AB  - Malaria, caused by parasites of the genus Plasmodium, leads to over half a
      million deaths per year, 90% of which are caused by Plasmodium falciparum. P.
      vivax usually causes milder forms of malaria; however, P. vivax can remain
      dormant in the livers of infected patients for weeks or years before re-emerging
      in a new bout of the disease. The only drugs available that target all stages of
      the parasite can lead to severe side effects in patients with glucose-6-phosphate
      dehydrogenase (G6PD) deficiency; hence, there is an urgent need to develop new
      drugs active against blood and liver stages of the parasite. Different groups
      have demonstrated that triclosan, a common antibacterial agent, targets the
      Plasmodium liver enzyme enoyl reductase. Here, we provide 4 independent lines of
      evidence demonstrating that triclosan specifically targets both wild-type and
      pyrimethamine-resistant P. falciparum and P. vivax dihydrofolate reductases,
      classic targets for the blood stage of the parasite. This makes triclosan an
      exciting candidate for further development as a dual specificity antimalarial,
      which could target both liver and blood stages of the parasite.

PMID- 29348639
TI  - Evidence of local structural influence on the shape driven magnetic anisotropy in
      electronically excited Ni nanoparticles embedded in SiO2 matrix.
AB  - The reliance of modern electronic era on ultrafast data recording has made the
      search for novel tools to tune nano-scale magnetic-anisotropy (MA) never-ending.
      We demonstrate a strong correlation between the spin-spin interactions, local
      atomic structure and the MA of Ni nanoparticles (NPs) embedded inside SiO2 matrix
      under swift heavy ion (SHI) irradiation. In contrast to traditional
      understandings, MA in Ni NPs along with their aspect ratio, first increases upto
      5 * 1013 ions/cm2 SHI fluence (5e13) and gets reduced at highest fluence. Using
      angle dependent Extented-Xray-Absorption-Fine-Structure (EXAFS) and ab initio
      molecular dynamics (MD) simulations, we show that the anisotropy induced in local
      atomic structure upon irradiation is dependent on atomic spin-spin interactions,
      which gets reduced at highest fluence. The chosen model cluster (Ni38) used in
      our MD simulations is duly validated by comparing the pair-correlation-function
      of the structure with the EXAFS-Fourier-Transform. The lattice temperatures for
      the films irradiated at different fluences, as calculated from thermal-spike
      model, are used for the respective MD runs. We conclude that the enhanced
      disorder in both the local atomic environment and spin alignment destroys the MA
      at the highest fluence in SHI irradiated Ni NPs. The findings therefore provide
      rich conceptual insights for designing magnetic devices using SHI-induced
      phenomena.

PMID- 29348640
TI  - Predators on top.

PMID- 29348638
TI  - Changes in cytokine responses to TB antigens ESAT-6, CFP-10 and TB 7.7 and
      inflammatory markers in peripheral blood during therapy.
AB  - Multiple cytokines and inflammatory markers control TB infection. We aimed to
      investigate the changes in multiple cytokines and inflammatory markers in active
      TB patients following anti-TB drug therapy. Twenty-nine patients with active TB
      were recruited prospectively between December 2010 and July 2017. Blood samples
      were collected before (T0), after 2 months (T2), and at the end of anti-TB
      treatment (Tend). We measured the levels of Interferon (IFN)-gamma, interleukin
      (IL)-2, IL-12, IL-10, IL-13 and tumor necrosis factor (TNF)-alpha in supernatants
      collected from the QuantiFERON-TB Gold In-Tube assay (QFT-GIT), as well as the
      WBC, neutrophil, platelet count and neutrophil to lymphocyte ratio (NLR) in whole
      blood. Compared with baseline levels, WBC, neutrophil, and platelet counts were
      significantly lower following treatment. In addition, the NLR after treatment
      significantly decreased compared with baseline, whereas the IL-2/IFN-gamma ratio
      increased after treatment. In conclusion, the levels of IL-2/IFN-gamma ratios in
      the supernatant and the NLR might be useful biomarkers to evaluate the
      effectiveness of drug therapy in active TB patients.

PMID- 29348641
TI  - Refined control of cell stemness allowed animal evolution in the oxic realm.
AB  - Animal diversification on Earth has long been presumed to be associated with the
      increasing extent of oxic niches. Here, we challenge that view. We start with the
      fact that hypoxia (<1-3% O2) maintains cellular immaturity (stemness), whereas
      adult stem cells continuously-and paradoxically-regenerate animal tissue in
      oxygenated settings. Novel insights from tumour biology illuminate how cell
      stemness nevertheless can be achieved through the action of oxygen-sensing
      transcription factors in oxygenated, regenerating tissue. We suggest that these
      hypoxia-inducible transcription factors provided animals with unprecedented
      control over cell stemness that allowed them to cope with fluctuating oxygen
      concentrations. Thus, a refinement of the cellular hypoxia-response machinery
      enabled cell stemness at oxic conditions and, then, animals to evolve into the
      oxic realm. This view on the onset of animal diversification is consistent with
      geological evidence and provides a new perspective on the challenges and
      evolution of multicellular life.

PMID- 29348642
TI  - The success of failed Homo sapiens dispersals out of Africa and into Asia.
AB  - The evidence for an early dispersal of Homo sapiens from Africa into the Levant
      during Marine Isotope Stage 5 (MIS-5) 126-74 ka (thousand years ago) was
      characterized for many years as an 'abortive' expansion: a precursor to a
      sustained dispersal from which all extant human populations can be traced. Recent
      archaeological and genetic data from both western and eastern parts of Eurasia
      and from Australia are starting to challenge that interpretation. This
      Perspective reviews the current evidence for a scenario where the MIS-5 dispersal
      encompassed a much greater geographic distribution and temporal duration. The
      implications of this for tracking and understanding early human dispersal in
      Southeast Asia specifically are considered, and the validity of measuring
      dispersal success only through genetic continuity into the present is examined.

PMID- 29348643
TI  - A trillion trees.

PMID- 29348644
TI  - Global priorities for conserving the evolutionary history of sharks, rays and
      chimaeras.
AB  - In an era of accelerated biodiversity loss and limited conservation resources,
      systematic prioritization of species and places is essential. In terrestrial
      vertebrates, evolutionary distinctness has been used to identify species and
      locations that embody the greatest share of evolutionary history. We estimate
      evolutionary distinctness for a large marine vertebrate radiation on a dated
      taxon-complete tree for all 1,192 chondrichthyan fishes (sharks, rays and
      chimaeras) by augmenting a new 610-species molecular phylogeny using taxonomic
      constraints. Chondrichthyans are by far the most evolutionarily distinct of all
      major radiations of jawed vertebrates-the average species embodies 26 million
      years of unique evolutionary history. With this metric, we identify 21 countries
      with the highest richness, endemism and evolutionary distinctness of threatened
      species as targets for conservation prioritization. On average, threatened
      chondrichthyans are more evolutionarily distinct-further motivating improved
      conservation, fisheries management and trade regulation to avoid significant
      pruning of the chondrichthyan tree of life.

PMID- 29348646
TI  - Intergenerational equity can help to prevent climate change and extinction.

PMID- 29348645
TI  - A global perspective on the trophic geography of sharks.
AB  - Sharks are a diverse group of mobile predators that forage across varied spatial
      scales and have the potential to influence food web dynamics. The ecological
      consequences of recent declines in shark biomass may extend across broader
      geographic ranges if shark taxa display common behavioural traits. By tracking
      the original site of photosynthetic fixation of carbon atoms that were ultimately
      assimilated into muscle tissues of 5,394 sharks from 114 species, we identify
      globally consistent biogeographic traits in trophic interactions between sharks
      found in different habitats. We show that populations of shelf-dwelling sharks
      derive a substantial proportion of their carbon from regional pelagic sources,
      but contain individuals that forage within additional isotopically diverse local
      food webs, such as those supported by terrestrial plant sources, benthic
      production and macrophytes. In contrast, oceanic sharks seem to use carbon
      derived from between 30 degrees  and 50 degrees  of latitude. Global-scale
      compilations of stable isotope data combined with biogeochemical modelling
      generate hypotheses regarding animal behaviours that can be tested with other
      methodological approaches.

PMID- 29348647
TI  - The contribution of predators and scavengers to human well-being.
AB  - Predators and scavengers are frequently persecuted for their negative effects on
      property, livestock and human life. Research has shown that these species play
      important regulatory roles in intact ecosystems including regulating herbivore
      and mesopredator populations that in turn affect floral, soil and hydrological
      systems. Yet predators and scavengers receive surprisingly little recognition for
      their benefits to humans in the landscapes they share. We review these benefits,
      highlighting the most recent studies that have documented their positive effects
      across a range of environments. Indeed, the benefits of predators and scavengers
      can be far reaching, affecting human health and well-being through disease
      mitigation, agricultural production and waste-disposal services. As many
      predators and scavengers are in a state of rapid decline, we argue that
      researchers must work in concert with the media, managers and policymakers to
      highlight benefits of these species and the need to ensure their long-term
      conservation. Furthermore, instead of assessing the costs of predators and
      scavengers only in economic terms, it is critical to recognize their beneficial
      contributions to human health and well-being. Given the ever-expanding human
      footprint, it is essential that we construct conservation solutions that allow a
      wide variety of species to persist in shared landscapes. Identifying, evaluating
      and communicating the benefits provided by species that are often considered
      problem animals is an important step for establishing tolerance in these shared
      spaces.

PMID- 29348649
TI  - Publisher Correction: Determination of total and unbound docetaxel in plasma by
      ultrafiltration and UPLC-MS/MS: application to pharmacokinetic studies.
AB  - A correction to this article has been published and is linked from the HTML
      version of this paper. The error has been fixed in the paper.

PMID- 29348648
TI  - Specific cyclic ADP-ribose phosphohydrolase obtained by mutagenic engineering of
      Mn2+-dependent ADP-ribose/CDP-alcohol diphosphatase.
AB  - Cyclic ADP-ribose (cADPR) is a messenger for Ca2+ mobilization. Its turnover is
      believed to occur by glycohydrolysis to ADP-ribose. However, ADP-ribose/CDP
      alcohol diphosphatase (ADPRibase-Mn) acts as cADPR phosphohydrolase with much
      lower efficiency than on its major substrates. Recently, we showed that
      mutagenesis of human ADPRibase-Mn at Phe37, Leu196 and Cys253 alters its
      specificity: the best substrate of the mutant F37A + L196F + C253A is cADPR by a
      short difference, Cys253 mutation being essential for cADPR preference. Its
      proximity to the 'northern' ribose of cADPR in docking models indicates Cys253 is
      a steric constraint for cADPR positioning. Aiming to obtain a specific cADPR
      phosphohydrolase, new mutations were tested at Asp250, Val252, Cys253 and Thr279,
      all near the 'northern' ribose. First, the mutant F37A + L196F + C253G, with a
      smaller residue 253 (Ala > Gly), showed increased cADPR specificity. Then, the
      mutant F37A + L196F + V252A + C253G, with another residue made smaller (Val >
      Ala), displayed the desired specificity, with cADPR kcat/KM ~20-200-fold larger
      than for any other substrate. When tested in nucleotide mixtures, cADPR was
      exhausted while others remained unaltered. We suggest that the specific cADPR
      phosphohydrolase, by cell or organism transgenesis, or the designed mutations, by
      genome editing, provide opportunities to study the effect of cADPR depletion on
      the many systems where it intervenes.

PMID- 29348650
TI  - Glacial vicariance drives phylogeographic diversification in the amphi-boreal
      kelp Saccharina latissima.
AB  - Glacial vicariance is regarded as one of the most prevalent drivers of
      phylogeographic structure and speciation among high-latitude organisms, but
      direct links between ice advances and range fragmentation have been more
      difficult to establish in marine than in terrestrial systems. Here we investigate
      the evolution of largely disjunct (and potentially reproductively isolated)
      phylogeographic lineages within the amphi-boreal kelp Saccharina latissima s. l.
      Using molecular data (COI, microsatellites) we confirm that S. latissima
      comprises also the NE Pacific S. cichorioides complex and is composed of
      divergent lineages with limited range overlap and genetic admixture. Only a few
      genetic hybrids were detected throughout a Canadian Arctic/NW Greenland contact
      zone. The degree of genetic differentiation and sympatric isolation of
      phylogroups suggest that S. latissima s. l. represents a complex of incipient
      species. Phylogroup distributions compared with paleo-environmental
      reconstructions of the cryosphere further suggest that diversification within S.
      latissima results from chronic glacial isolation in disjunct persistence areas
      intercalated with ephemeral interglacial poleward expansions and admixture at
      high-latitude (Arctic) contact zones. This study thus supports a role for
      glaciations not just in redistributing pre-existing marine lineages but also as a
      speciation pump across multi-glacial cycles for marine organisms otherwise
      exhibiting cosmopolite amphi-boreal distributions.

PMID- 29348652
TI  - Intensification of ice nucleation observed in ocean ship emissions.
AB  - Shipping contributes primary and secondary emission products to the atmospheric
      aerosol burden that have implications for climate, clouds, and air quality from
      regional to global scales. In this study we exam the potential impact of ship
      emissions with regards to ice nucleating particles. Particles that nucleate ice
      are known to directly affect precipitation and cloud microphysical properties. We
      have collected and analyzed particles for their ice nucleating capacity from a
      shipping channel outside a large Scandinavia port. We observe that ship plumes
      amplify the background levels of ice nucleating particles and discuss the larger
      scale implications. The measured ice nucleating particles suggest that the
      observed amplification is most likely important in regions with low levels of
      background particles. The Arctic, which as the sea ice pack declines is opening
      to transit and natural resource exploration and exploitation at an ever
      increasing rate, is highlighted as such a region.

PMID- 29348651
TI  - Depressive mood ratings are reduced by MDMA in female polydrug ecstasy users
      homozygous for the l-allele of the serotonin transporter.
AB  - MDMA exerts its main effects via the serotonergic system and the serotonin
      transporter. The gene coding for this transporter determines the expression rate
      of the transporter. Previously it was shown that healthy individuals with the
      short allelic variant ('s-group') of the 5-HTTLPR-polymorphism displayed more
      anxiety and negative mood, and had a lower transcriptional efficiency compared to
      individuals who are homozygous for the l-allele ('l-group'). The present study
      aimed to investigate the role of the 5-HTTLPR polymorphism in MDMA-induced mood
      effects. Four placebo-controlled, within-subject studies were pooled, including
      in total 63 polydrug ecstasy users (Ns-group = 48; Nl-group = 15) receiving MDMA
      75 mg and placebo on two test days, separated by minimally 7 days. Mood was
      assessed by means of the Profile of Mood States. Findings showed that MDMA
      induced -independent of sex- a positive mood state, and as a side effect also
      increased two negative affect states, anxiety and confusion. Anxiety ratings were
      higher in the l-group and independent of treatment or sex. Depression ratings
      were lowered by MDMA in the female l-group. Findings indicate that the MDMA
      induced reduction in self-rated depressive feelings is sex- and genotype
      dependent, with females homozygous for the l-allele showing this beneficial
      effect.

PMID- 29348653
TI  - Non-structural carbohydrates regulated by season and species in the subtropical
      monsoon broad-leaved evergreen forest of Yunnan Province, China.
AB  - Non-structural carbohydrates (NSC) play important roles in adapting to
      environments in plants. Despite extensive research on the seasonal dynamics and
      species differences of NSC, the relative contributions of season and species to
      NSC is not well understood. We measured the concentration of starch, soluble
      sugar, NSC, and the soluble sugar:starch ratio in leaves, twigs, trunks and roots
      of twenty dominant species for dry and wet season in monsoon broad-leaved
      evergreen forest, respectively. The majority of concentration of NSC and starch
      in the roots, and the leaves contained the highest concentration of soluble
      sugar. A seasonal variation in starch and NSC concentrations higher in the dry
      season. Conversely, the wet season samples had higher concentration of soluble
      sugar and the sugar:starch ratio. Significant differences exist for starch,
      soluble sugar and NSC concentrations and the sugar:starch ratio across species.
      Most species had higher starch and NSC concentrations in the dry season and
      higher soluble sugar concentration and the sugar:starch ratio in wet season.
      Repeated variance analysis showed that starch and NSC concentrations were
      strongly affected by season although the effect of seasons, species, and the
      interaction of the two on the starch, soluble sugar, and NSC concentrations were
      significant.

PMID- 29348655
TI  - The headache of temporomandibular disorders.
AB  - This article endeavours to revise the key guidance and evidence on
      temporomandibular disorders (TMD), with a particular focus on myofascial pain. It
      highlights the important role that primary care dental practitioners play in
      providing holistic care during the patient's journey to manage this painful
      condition. I hope to give an insight into my own personal experiences to
      highlight the challenges patients can face in seeking appropriate support.

PMID- 29348654
TI  - Low concentration trifluoperazine promotes proliferation and reduces calcium
      dependent apoptosis in glioma cells.
AB  - Glioma patients constitute the greatest percentage of depressed neoplasm
      patients. These patients often require antidepressant treatment, but the effect
      of antidepressant drugs on glioma cells requires further evaluation. In the
      present study, we evaluated the effect of trifluoperazine (TFP) on the
      proliferation and apoptosis of glioma cells. Transcriptomic and bioinformatics
      analysis results suggested that antidepressant drugs, especially TFP, may
      upregulate the drug-resistant ability of glioma cells. A low concentration of TFP
      upregulated the viability of glioma cells. Colony formation and EdU assays
      confirmed that TFP treatment accelerates glioma cell proliferation, but no
      significant difference was found in the cell cycle distribution of glioma cells
      after treatment with TFP or control. Flow cytometry and TUNEL staining results
      suggested that TFP treatment decreased apoptosis in glioma cells. In addition,
      TFP treatment downregulated the intracellular Ca2+ concentration of glioma cells.
      In vivo experimental results indicated that TFP treatment promoted proliferation
      and reduced apoptosis in xenograft tumours in nude mice. Taken together, our
      results suggest that a low concentration of TFP promotes proliferation and
      reduces apoptosis in glioma cells both in vitro and in vivo. The potential
      harmful effects of antidepressant drugs on gliomas require further evaluation
      before their use in glioma patients.

PMID- 29348656
TI  - Quantifying the Risk and Cost of Active Monitoring for Infectious Diseases.
AB  - During outbreaks of deadly emerging pathogens (e.g., Ebola, MERS-CoV) and
      bioterror threats (e.g., smallpox), actively monitoring potentially infected
      individuals aims to limit disease transmission and morbidity. Guidance issued by
      CDC on active monitoring was a cornerstone of its response to the West Africa
      Ebola outbreak. There are limited data on how to balance the costs and
      performance of this important public health activity. We present a framework that
      estimates the risks and costs of specific durations of active monitoring for
      pathogens of significant public health concern. We analyze data from New York
      City's Ebola active monitoring program over a 16-month period in 2014-2016. For
      monitored individuals, we identified unique durations of active monitoring that
      minimize expected costs for those at "low (but not zero) risk" and "some or high
      risk": 21 and 31 days, respectively. Extending our analysis to smallpox and MERS
      CoV, we found that the optimal length of active monitoring relative to the median
      incubation period was reduced compared to Ebola due to less variable incubation
      periods. Active monitoring can save lives but is expensive. Resources can be most
      effectively allocated by using exposure-risk categories to modify the duration or
      intensity of active monitoring.

PMID- 29348657
TI  - An ethylene response factor (MxERF4) functions as a repressor of Fe acquisition
      in Malus xiaojinensis.
AB  - Iron (Fe) is an essential element for plants; however, its availability is
      limited as it forms insoluble complexes in the soil. Consequently, plants have
      developed mechanisms to adapt to low Fe conditions. We demonstrate that ethylene
      is involved in Fe deficiency-induced physiological responses in Malus
      xiaojinensis, and describe the identification of MxERF4 as a protein-protein
      interaction partner with the MxFIT transcription factor, which is involved in the
      iron deficiency response. Furthermore, we demonstrate that MxERF4 acts as an
      MxFIT interaction partner to suppresses the expression of the Fe transporter
      MxIRT1, by binding directly to its promoter, requiring the EAR motif of the
      MxERF4 protein. Suppression of MxERF4 expression in M. xiaojinensis, using virus
      induced gene silencing resulted in an increase in MxIRT1 expression. Taken
      together, the results suggest a repression mechanism, where ethylene initiates
      the Fe deficiency response, and the response is then dampened, which may require
      a transient inhibition of Fe acquisition via the action of MxERF4.

PMID- 29348658
TI  - Novel multifunctional cheese-like 3D carbon-BN as a highly efficient adsorbent
      for water purification.
AB  - In this paper, a novel three dimensional carbon boron nitride (3D C-BN) was
      successfully prepared. The obtained material has porous cheese-like structure and
      pore size ranging from 2 nm to 100 nm. Attractively, the 3D C-BN, which combines
      the adsorption advantages of BN and carbon together, exhibits excellent
      adsorption properties for organic dyes, oils and heavy metal ions. The maximum
      removal capacities of 3D C-BN for methyl blue (MB) and congo red (CR) are 408 mg
      g-1 and 307 mg g-1, respectively. Furthermore, 3D C-BN can quickly and
      efficiently remove oils (salad oil, gasoline and pump oil) and heavy metal ions
      (Cr3+, Cd2+ and Ni2+) from waste water. The macro bulk 3D C-BN, which is more
      convenient to use than powdered materials, can be reused by burning or heating in
      air and still maintains high adsorption capacity. Significantly, these superior
      performances can find practical application in water purification.

PMID- 29348659
TI  - BLM helicase suppresses recombination at G-quadruplex motifs in transcribed
      genes.
AB  - Bloom syndrome is a cancer predisposition disorder caused by mutations in the BLM
      helicase gene. Cells from persons with Bloom syndrome exhibit striking genomic
      instability characterized by excessive sister chromatid exchange events (SCEs).
      We applied single-cell DNA template strand sequencing (Strand-seq) to map the
      genomic locations of SCEs. Our results show that in the absence of BLM, SCEs in
      human and murine cells do not occur randomly throughout the genome but are
      strikingly enriched at coding regions, specifically at sites of guanine
      quadruplex (G4) motifs in transcribed genes. We propose that BLM protects against
      genome instability by suppressing recombination at sites of G4 structures,
      particularly in transcribed regions of the genome.

PMID- 29348660
TI  - Generation and Characterization of Alloantigen-Specific Regulatory T Cells For
      Clinical Transplant Tolerance.
AB  - Donor-specific CD4+CD127-CD25+FOXP3+ regulatory T cells (AgTregs) have the
      potential to induce clinical transplant tolerance; however, their expansion ex
      vivo remains challenging. We optimized a novel expansion protocol to stimulate
      donor-specific Tregs using soluble 4-trimer CD40 ligand (CD40L)-activated donor B
      cells that expressed mature antigen-presenting cell markers. This avoided the use
      of CD40L-expressing stimulator cells that might otherwise result in potential
      cellular contamination. Purified allogeneic "recipient" CD4+CD25+ Tregs were
      stimulated on days 0 and 7 with expanded "donor" B cells in the presence of IL-2,
      TGFbeta and sirolimus (SRL). Tregs were further amplified by polyclonal
      stimulation with anti-CD3/CD28 beads on day 14 without SRL, and harvested on day
      21, with extrapolated fold expansion into the thousands. The expanded AgTregs
      maintained expression of classical Treg markers including demethylation of the
      Treg-specific demethylated region (CNS2) and also displayed constricted TcR
      repertoire. We observed AgTregs more potently inhibited MLR than polyclonally
      expanded Tregs and generated new Tregs in autologous responder cells (a measure
      of infectious tolerance). Thus, an optimized and more clinically applicable
      protocol for the expansion of donor-specific Tregs has been developed.

PMID- 29348661
TI  - Highly efficient and stable inverted perovskite solar cell employing PEDOT:GO
      composite layer as a hole transport layer.
AB  - The beneficial use of a hole transport layer (HTL) as a substitution for poly(3,4
      ethlyenedioxythiophene): polystyrene sulfonate (PEDOT:PSS) is regarded as one of
      the most important approaches for improving the stability and efficiency of
      inverted perovskite solar cells. Here, we demonstrate highly efficient and stable
      inverted perovskite solar cells by applying a GO-doped PEDOT:PSS (PEDOT:GO) film
      as an HTL. The high performance of this solar cell stems from the excellent
      optical and electrical properties of the PEDOT:GO film, including a higher
      electrical conductivity, a higher work function related to the reduced contact
      barrier between the perovskite layer and the PEDOT:GO layer, enhanced
      crystallinity of the perovskite crystal, and suppressed leakage current.
      Moreover, the device with the PEDOT:GO layer showed excellent long-term stability
      in ambient air conditions. Thus, the enhancement in the efficiency and the
      excellent stability of inverted perovskite solar cells are promising for the
      eventual commercialization of perovskite optoelectronic devices.

PMID- 29348662
TI  - Endoscopic submucosal tunnel dissection using a novel bracing basket: An animal
      feasibility study.
AB  - The aim of this study was to evaluate the feasibility of a novel bracing basket
      for Endoscopic submucosal tunnel dissection (ESTD), which was developed for
      improved effectiveness and ease of use. This was a prospective randomized,
      comparative, experimental animal study carried out at a single center. The
      primary aim was to evaluate the efficacy of ESTD with a novel bracing basket,
      compared with conventional ESTD. The secondary aims were to assess the quality
      control of the procedures and adverse events. Twenty procedures (6 esophageal and
      14 gastric) were performed in four pigs. All resections were completed as en bloc
      resections. The technical success rate was 100% for both techniques (bracing
      basket-assisted ESTD vs. conventional ESTD). The procedure times were similar,
      but the cutting speed was quicker with bracing basket-assisted ESTD in gastric
      (antrum:23.3 +/- 2.2 mm2/min vs. 15.2 +/- 3.2 mm2/min, body: 26.1 +/- 1.3 mm2/min
      vs. 18.4 +/- 2.0 mm2/min, p < 0.05). There was one bleeding in the bracing basket
      assisted ESTD group and one perforation in the conventional ESTD group. Compared
      with conventional ESTD, the use of this basket has potential advantages.
      Comparison studies with larger gastric or colorectal lesions treated with
      conventional ESTD are needed.

PMID- 29348663
TI  - Enhancer-associated long non-coding RNA LEENE regulates endothelial nitric oxide
      synthase and endothelial function.
AB  - The optimal expression of endothelial nitric oxide synthase (eNOS), the hallmark
      of endothelial homeostasis, is vital to vascular function. Dynamically regulated
      by various stimuli, eNOS expression is modulated at transcriptional, post
      transcriptional, and post-translational levels. However, epigenetic modulations
      of eNOS, particularly through long non-coding RNAs (lncRNAs) and chromatin
      remodeling, remain to be explored. Here we identify an enhancer-associated lncRNA
      that enhances eNOS expression (LEENE). Combining RNA-sequencing and chromatin
      conformation capture methods, we demonstrate that LEENE is co-regulated with eNOS
      and that its enhancer resides in proximity to eNOS promoter in endothelial cells
      (ECs). Gain- and Loss-of-function of LEENE differentially regulate eNOS
      expression and EC function. Mechanistically, LEENE facilitates the recruitment of
      RNA Pol II to the eNOS promoter to enhance eNOS nascent RNA transcription. Our
      findings unravel a new layer in eNOS regulation and provide novel insights into
      cardiovascular regulation involving endothelial function.

PMID- 29348664
TI  - Stress-induced TRBP phosphorylation enhances its interaction with PKR to regulate
      cellular survival.
AB  - Transactivation response element RNA-binding protein (TRBP or TARBP2) initially
      identified to play an important role in human immunodeficiency virus (HIV)
      replication also has emerged as a regulator of microRNA biogenesis. In addition,
      TRBP functions in signaling pathways by negatively regulating the interferon
      induced double-stranded RNA (dsRNA)-activated protein kinase (PKR) during viral
      infections and cell stress. During cellular stress, PKR is activated and
      phosphorylates the alpha subunit of the eukaryotic translation factor eIF2,
      leading to the cessation of general protein synthesis. TRBP inhibits PKR activity
      by direct interaction as well as by binding to PKR's two known activators, dsRNA
      and PACT, thus preventing their interaction with PKR. In this study, we
      demonstrate for the first time that TRBP is phosphorylated in response to
      oxidative stress and upon phosphorylation, inhibits PKR more efficiently
      promoting cell survival. These results establish that PKR regulation through
      stress-induced TRBP phosphorylation is an important mechanism ensuring cellular
      recovery and preventing apoptosis due to sustained PKR activation.

PMID- 29348665
TI  - PCDHGA9 acts as a tumor suppressor to induce tumor cell apoptosis and autophagy
      and inhibit the EMT process in human gastric cancer.
AB  - The results of a cDNA  array revealed that protocadherin gamma subfamily A, 9
      (PCDHGA9) was significantly decreased in SGC-7901 gastric cancer (GC) cells
      compared with GES-1 normal gastric cells and was strongly associated with the
      Wnt/beta-catenin and transforming growth factor-beta (TGF-beta)/Smad2/3 signaling
      pathway. As a member of the cadherin family, PCDHGA9 functions in both cell-cell
      adhesion and nuclear signaling. However, its role in tumorigenicity or metastasis
      has not been reported. In the present study, we found that PCDHGA9 was decreased
      in GC tissues compared with corresponding normal mucosae and its expression was
      correlated with the GC TNM stage, the UICC stage, differentiation, relapse, and
      metastasis (p < 0.01). Multivariate Cox analysis revealed that PCDHGA9 was an
      independent prognostic indicator for overall survival (OS) and disease-free
      survival (DFS) (p < 0.01). The effects of PCDHGA9 on GC tumor growth and
      metastasis were examined both in vivo and in vitro. PCDHGA9 knockdown promoted GC
      cell proliferation, migration, and invasion, whereas PCDHGA9 overexpression
      inhibited GC tumor growth and metastasis but induced apoptosis, autophagy, and G1
      cell cycle arrest. Furthermore, PCDHGA9 suppressed epithelial-mesenchymal
      transition (EMT) induced by TGF-beta, decreased the phosphorylation of Smad2/3,
      and inhibited the nuclear translocation of pSmad2/3. Our results suggest that
      PCDHGA9 might interact with beta-catenin to prevent beta-catenin from
      dissociating in the cytoplasm and translocating to the nucleus. Moreover, PCDHGA9
      overexpression restrained cell proliferation and reduced the nuclear beta
      catenin, an indicator of Wnt/beta-catenin pathway activation, suggesting that
      PCDHGA9 negatively regulates Wnt signaling. Together, these data indicate that
      PCDHGA9 acts as a tumor suppressor with anti-proliferative activity and anti
      invasive ability, and the reduction of PCDHGA9 could serve as an independent
      prognostic biomarker in GC.

PMID- 29348667
TI  - Neuroimmunology: Brain police.

PMID- 29348668
TI  - Neurodegenerative disease: A proteostatic boost.

PMID- 29348669
TI  - Learning and memory: You only learn once.

PMID- 29348666
TI  - Mitochondria at the neuronal presynapse in health and disease.
AB  - Synapses enable neurons to communicate with each other and are therefore a
      prerequisite for normal brain function. Presynaptically, this communication
      requires energy and generates large fluctuations in calcium concentrations.
      Mitochondria are optimized for supplying energy and buffering calcium, and they
      are actively recruited to presynapses. However, not all presynapses contain
      mitochondria; thus, how might synapses with and without mitochondria differ?
      Mitochondria are also increasingly recognized to serve additional functions at
      the presynapse. Here, we discuss the importance of presynaptic mitochondria in
      maintaining neuronal homeostasis and how dysfunctional presynaptic mitochondria
      might contribute to the development of disease.

PMID- 29348671
TI  - Superconducting gap anisotropy sensitive to nematic domains in FeSe.
AB  - The structure of the superconducting gap in unconventional superconductors holds
      a key to understand the momentum-dependent pairing interactions. In
      superconducting FeSe, there have been controversial results reporting nodal and
      nodeless gap structures, raising a fundamental issue of pairing mechanisms of
      iron-based superconductivity. Here, by utilizing polarization-dependent laser
      excited angle-resolved photoemission spectroscopy, we report a detailed momentum
      dependence of the gap in single- and multi-domain regions of orthorhombic FeSe
      crystals. We confirm that the superconducting gap has a twofold in-plane
      anisotropy, associated with the nematicity due to orbital ordering. In twinned
      regions, we clearly find finite gap minima near the vertices of the major axis of
      the elliptical zone-centered Fermi surface, indicating a nodeless state. In
      contrast, the single-domain gap drops steeply to zero in a narrow angle range,
      evidencing for nascent nodes. Such unusual node lifting in multi-domain regions
      can be explained by the nematicity-induced time-reversal symmetry breaking near
      the twin boundaries.

PMID- 29348670
TI  - Intradermal delivery of STAT3 siRNA to treat melanoma via dissolving
      microneedles.
AB  - Hyperactivity of signal transducer and activity of transcription 3 (STAT3) plays
      a crucial role in melanoma invasion and metastasis. Gene therapy applying siRNA
      targeting STAT3 is a potential therapeutic strategy for melanoma. In this
      article, we first fabricated safe and novel dissolving microneedles (MNs) for
      topical application of STAT3 siRNA to enhance the skin penetration of siRNA and
      used polyethylenimine (PEI, 25 kDa) as carrier to improve cellular uptake of
      siRNA. The results showed that MNs can effectively penetrate skin and rapidly
      dissolve in the skin. In vitro B16F10 cell experiments presented that STAT3 siRNA
      PEI complex can enhance cellular uptake and transfection of siRNA,
      correspondingly enhance gene silencing efficiency and inhibit tumor cells growth.
      In vivo experiments indicated that topical application of STAT3 siRNA PEI complex
      delivered by dissolving MNs into skin can effectively suppress the development of
      melanoma through silencing STAT3 gene, and the inhibition effect is dose
      dependent. STAT3 siRNA delivery via dissolving MNs is a promising approach for
      skin melanoma treatment with targeting inhibition efficacy and minimal adverse
      effects.

PMID- 29348672
TI  - Soluble LRP1 is an independent biomarker of epicardial fat volume in patients
      with type 1 diabetes mellitus.
AB  - Epicardial adipose tissue (EAT) is a metabolically active tissue intimately
      associated with metabolic syndrome and cardiovascular disease. Quantification of
      EAT volume is an interesting clinical tool for the evaluation of cardiometabolic
      disease. Nevertheless, current methodology presents serious disadvantages. The
      soluble form of the receptor LRP1 (sLRP1) is a non-invasive biomarker of EAT in
      general population. Here, we analysed the potential of circulating sLRP1 as
      biomarker of EAT volume in patients with type 1 diabetes mellitus (T1DM). The
      study included a well-characterized cohort of T1DM patients without clinical
      cardiovascular disease (N = 73). EAT volume was assessed by a multidetector
      computed tomography (MDCT). sLRP1 and panel of inflammatory and endocrine
      mediators were measured using commercially available ELISA. EAT volume showed a
      direct association with circulating sLRP1 (beta = 0.398, P = 0.001) in univariate
      linear regression analysis. This association was higher than that observed for
      other potential inflammatory and endocrine biomarkers. Using multivariate linear
      regression analyses, we demonstrated that the association between EAT volume and
      circulating sLRP1 was independent of potential confounding factors, including
      age, sex, body mass index, CRP, HbA1c and LDL-C (P < 0.050 for all multivariate
      linear regression models). In conclusion, sLRP1 is an independent biomarker of
      EAT in T1DM patients.

PMID- 29348673
TI  - Quantification of massively parallel sequencing libraries - a comparative study
      of eight methods.
AB  - Quantification of massively parallel sequencing libraries is important for
      acquisition of monoclonal beads or clusters prior to clonal amplification and to
      avoid large variations in library coverage when multiple samples are included in
      one sequencing analysis. No gold standard for quantification of libraries exists.
      We assessed eight methods of quantification of libraries by quantifying 54
      amplicon, six capture, and six shotgun fragment libraries. Chemically synthesized
      double-stranded DNA was also quantified. Light spectrophotometry, i.e. NanoDrop,
      was found to give the highest concentration estimates followed by Qubit and
      electrophoresis-based instruments (Bioanalyzer, TapeStation, GX Touch, and
      Fragment Analyzer), while SYBR Green and TaqMan based qPCR assays gave the lowest
      estimates. qPCR gave more accurate predictions of sequencing coverage than Qubit
      and TapeStation did. Costs, time-consumption, workflow simplicity, and ability to
      quantify multiple samples are discussed. Technical specifications, advantages,
      and disadvantages of the various methods are pointed out.

PMID- 29348674
TI  - Variation at position 350 in the Chikungunya virus 6K-E1 protein determines the
      sensitivity of detection in a rapid E1-antigen test.
AB  - Chikungunya virus (CHIKV), a mosquito-borne pathogen, consists of three
      genotypes: East/Central/South African (ECSA), West African (WA), and Asian.
      Although a current rapid immunochromatographic (IC) test detecting CHIKV E1
      antigen showed high sensitivity to ECSA-genotype viruses, it showed poor
      performance against the Asian-genotype virus that is spreading in the American
      continents. To understand the basis for the low performance of this IC test
      against Asian-genotype virus, we re-examined the anti-CHIKV monoclonal antibodies
      (mAbs) used in the assay for their interaction with E1-antigen of the three CHIKV
      genotypes. We found that the reactivity of one mAb for Asian-genotype virus was
      lower than that for ECSA virus. Comparison of E1 amino acid sequences revealed
      that the ECSA virus used to generate these mAbs possesses glutamic acid (E) at
      position 350, in contrast to WA and Asian, which possess aspartic acid (D) at
      this position. Site-directed mutagenesis confirmed that the mutation altered mAb
      reactivity, since E-to-D substitution at position 350 in ECSA reduced recognition
      by the mAb, while D-to-E substitution at this position in Asian and WA increased
      affinity for the mAb. Taken together, these results indicate that residue 350 of
      the CHIKV 6K-E1 is a key element affecting the performance of this IC assay.

PMID- 29348675
TI  - STAC2 negatively regulates osteoclast formation by targeting the RANK signaling
      complex.
AB  - The receptor activator of nuclear factor-kappaB (RANK) protein activates various
      protein kinase signaling cascades, including those involving NF-kappaB, mitogen
      activated protein kinase (MAPK), and Bruton tyrosine kinase (Btk)/tyrosine
      protein kinase Tec. However, the mechanism underlying the negative regulation of
      RANK by downstream signaling molecules remains unclear. Here, we report that Src
      homology 3 domain and cysteine-rich domain-containing protein 2 (STAC2) is a
      novel RANK ligand-inducible protein that negatively regulates RANK-mediated
      osteoclast formation. STAC2 physically interacts with RANK and inhibits the
      formation of the RANK signaling complex, which contains Grb-2-associated binder 2
      (Gab2) and phospholipase Cgamma2 (PLCgamma2), thus leading to the suppression of
      RANK-mediated NF-kappaB and MAPK activation. Furthermore, STAC2 overexpression
      limits Btk/Tec-mediated PLCgamma2 phosphorylation via the interaction between
      STAC2 and Btk/Tec. Taken together, our results reveal a novel mechanism whereby
      RANK signaling is restricted by its physical interaction with STAC2.

PMID- 29348676
TI  - miR-137 regulates ferroptosis by targeting glutamine transporter SLC1A5 in
      melanoma.
AB  - Ferroptosis is a regulated form of cell death driven by small molecules or
      conditions that induce lipid-based reactive oxygen species (ROS) accumulation.
      This form of iron-dependent cell death is morphologically and genetically
      distinct from apoptosis, necroptosis, and autophagy. miRNAs are known to play
      crucial roles in diverse fundamental biological processes. However, to date no
      study has reported miRNA-mediated regulation of ferroptosis. Here we show that
      miR-137 negatively regulates ferroptosis by directly targeting glutamine
      transporter SLC1A5 in melanoma cells. Ectopic expression of miR-137 suppressed
      SLC1A5, resulting in decreased glutamine uptake and malondialdehyde (MDA)
      accumulation. Meanwhile, antagomir-mediated inactivation of endogenous miR-137
      increased the sensitivity of melanoma cells to erastin- and RSL3-induced
      ferroptosis. Importantly, knockdown of miR-137 increased the antitumor activity
      of erastin by enhancing ferroptosis both in vitro and in vivo. Collectively,
      these data indicate that miR-137 plays a novel and indispensable role in
      ferroptosis by inhibiting glutaminolysis and suggest a potential therapeutic
      approach for melanoma.

PMID- 29348678
TI  - 2017 FDA drug approvals.

PMID- 29348677
TI  - The Proliferation Capacity of Cultured Neural Stem Cells Promoted by CSF
      Collected from SAH Patients Correlates to Clinical Outcome.
AB  - Neurogenesis from endogenous neural stem cells (NSCs) might contribute to
      functional recovery after stroke based on animal studies; however, the
      relationship between neurogenesis and post-stroke outcome has rarely been
      demonstrated in humans. We prospectively collected cerebrospinal fluid (CSF) from
      36 patients with subarachnoid hemorrhage (SAH). The CSF was added to the culture
      medium of the rat NSCs to test the effects on proliferation (proliferation index
      [PI], percentage of Ki-67 immunoreactive cells). We correlated the PI with
      functional outcome based on the modified Rankin Scale at 3 months post-SAH.
      Treatment with the CSF samples collected from SAH patients showed a higher PI
      compared with those collected from patients with normal pressure hydrocephalus
      and untreated controls (20.3 +/- 8.8 vs. 8.2 +/- 5.1 and 7.8 +/- 3.0, P < 0.001),
      indicating proliferation-promoting factors in CSF after SAH. The PI was
      positively correlated with SAH volume (p = 0.025). For patients with lower SAH
      volume, patients with favorable outcome had a higher PI than those with poor
      outcome (20.8 +/- 6.9 vs. 14.6 +/- 4.3, p = 0.047). Using multivariable logistic
      regression analysis, the PI was a positive determinant for favorable outcome
      (odds ratio, 1.17; 95% confidence interval, 1.00 to 1.36) that more proliferation
      promoting factors in CSF was associated with better functional outcome in SAH
      patients.

PMID- 29348679
TI  - Market watch: 2017 FDA drug approvals: number rebounds but average value slips.

PMID- 29348680
TI  - Morgan Sheng.

PMID- 29348682
TI  - Glimmers in illuminating the druggable genome.

PMID- 29348681
TI  - Impact of a five-dimensional framework on R&D productivity at AstraZeneca.
AB  - In 2011, AstraZeneca embarked on a major revision of its research and development
      (R&D) strategy with the aim of improving R&D productivity, which was below
      industry averages in 2005-2010. A cornerstone of the revised strategy was to
      focus decision-making on five technical determinants (the right target, right
      tissue, right safety, right patient and right commercial potential). In this
      article, we describe the progress made using this '5R framework' in the hope that
      our experience could be useful to other companies tackling R&D productivity
      issues. We focus on the evolution of our approach to target validation, hit and
      lead optimization, pharmacokinetic/pharmacodynamic modelling and drug safety
      testing, which have helped improve the quality of candidate drug nomination, as
      well as the development of the right culture, where 'truth seeking' is encouraged
      by more rigorous and quantitative decision-making. We also discuss where the
      approach has failed and the lessons learned. Overall, the continued evolution and
      application of the 5R framework are beginning to have an impact, with success
      rates from candidate drug nomination to phase III completion improving from 4% in
      2005-2010 to 19% in 2012-2016.

PMID- 29348683
TI  - The effect of foreign language in fear acquisition.
AB  - Emotions are at the core of human nature. There is evidence that emotional
      reactivity in foreign languages compared to native languages is reduced. We
      explore whether this emotional distance could modulate fear conditioning, an
      essential mechanism for the understanding and treatment of anxiety disorders. A
      group of participants was verbally informed (either in a foreign or in a native
      language) that two different stimuli could be either cueing the potential
      presence of a threat stimulus or its absence. We registered pupil size and
      electrodermal activity and calculated the difference in psychophysiological
      responses to conditioned and to unconditioned stimuli. Our findings provided
      evidence that verbal conditioning processes are affected by language context in
      this paradigm. We report the first experimental evidence regarding how the use of
      a foreign language may reduce fear conditioning. This observation opens the
      avenue to the potential use of a foreign language in clinical contexts.

PMID- 29348684
TI  - Mithramycin A suppresses basal triple-negative breast cancer cell survival
      partially via down-regulating Kruppel-like factor 5 transcription by Sp1.
AB  - As the most malignant breast cancer subtype, triple-negative breast cancer (TNBC)
      does not have effective targeted therapies clinically to date. As a selective Sp1
      inhibitor, Mithramycin A (MIT) has been reported to have anti-tumor activities in
      multiple cancers. However, the efficacy and the mechanism of MIT in breast
      cancer, especially TNBC, have not been studied. In this study, we demonstrated
      that MIT suppressed breast cancer cell survival in a dosage-dependent manner.
      Interestingly, TNBC cells were more sensitive to MIT than non-TNBC cells. MIT
      inhibited TNBC cell proliferation and promoted apoptosis in vitro in time- and
      dosage-dependent manners. MIT suppressed TNBC cell survival, at least partially,
      by transcriptionally down-regulating KLF5, an oncogenic transcription factor
      specifically expressed in basal TNBC. Finally, MIT suppressed TNBC cell growth in
      a xenograft mouse model. Taken together, our findings suggested that MIT inhibits
      basal TNBC via the Sp1/KLF5 axis and that MIT may be used for TNBC treatment.

PMID- 29348685
TI  - Overexpression of adhesion molecules and barrier molecules is associated with
      differential infiltration of immune cells in non-small cell lung cancer.
AB  - Immunotherapy is emerging as a promising option for lung cancer treatment.
      Various endothelial adhesion molecules, such as integrin and selectin, as well as
      various cellular barrier molecules such as desmosome and tight junctions,
      regulate T-cell infiltration in the tumor microenvironment. However, little is
      known regarding how these molecules affect immune cells in patients with lung
      cancer. We demonstrated for the first time that overexpression of endothelial
      adhesion molecules and cellular barrier molecule genes was linked to differential
      infiltration of particular immune cells in non-small cell lung cancer.
      Overexpression of endothelial adhesion molecule genes is associated with
      significantly lower infiltration of activated CD4 and CD8 T-cells, but higher
      infiltration of activated B-cells and regulatory T-cells. In contrast,
      overexpression of desmosome genes was correlated with significantly higher
      infiltration of activated CD4 and CD8 T-cells, but lower infiltration of
      activated B-cells and regulatory T-cells in lung adenocarcinoma. This inverse
      relation of immune cells aligns with previous studies of tumor-infiltrating B
      cells inhibiting T-cell activation. Although overexpression of endothelial
      adhesion molecule or cellular barrier molecule genes alone was not predictive of
      overall survival in our sample, these genetic signatures may serve as biomarkers
      of immune exclusion, or resistance to T-cell mediated immunotherapy.

PMID- 29348687
TI  - Far field superfocusing along with enhanced near field emission from hybrid
      spiral plasmonic lens inscribed with nano corrals slit diffractor.
AB  - Here, we have numerically calculated electric field intensity and phase of the
      emission from various hybrid spiral plasmonic lenses (HSPL) in near field as well
      as in far-field. We have proposed a novel HSPL inscribed with nano corrals slit
      (NCS) and compared its focusing ability with other HSPLs inscribed with circular
      slit and circular grating. With the use of nano corrals slit, we have been able
      to improve light intensity in the far-field without compromising near-field
      intensity. Our NCS-HSPL outperforms other HSPLs and standalone SPL in near-field
      as well as far-field. We have also found that proposed circular slit diffractor
      is far more superior than previously reported circular grating diffractor. We
      have been able to extend the focal length of hybrid plasmonic lens upto 3 um and
      observed a two-fold increment in the far field intensity compared to existing
      spiral plasmonic lens even though size of focal spot remains same. Optical
      complex fields produced by NCS based HSPL can be used for various applications
      such as super resolution microscopy, nanolithography, bioimaging and sensing,
      angular momentum detectors, etc. Moreover, enhanced near-field intensity in
      conjunction with far-field superfocusing with reasonable focal length may lead to
      the development of novel multifunctional lab-on-chip devices.

PMID- 29348686
TI  - Defects in the mitochondrial-tRNA modification enzymes MTO1 and GTPBP3 promote
      different metabolic reprogramming through a HIF-PPARgamma-UCP2-AMPK axis.
AB  - Human proteins MTO1 and GTPBP3 are thought to jointly catalyze the modification
      of the wobble uridine in mitochondrial tRNAs. Defects in each protein cause
      infantile hypertrophic cardiomyopathy with lactic acidosis. However, the
      underlying mechanisms are mostly unknown. Using fibroblasts from an MTO1 patient
      and MTO1 silenced cells, we found that the MTO1 deficiency is associated with a
      metabolic reprogramming mediated by inactivation of AMPK, down regulation of the
      uncoupling protein 2 (UCP2) and transcription factor PPARgamma, and activation of
      the hypoxia inducible factor 1 (HIF-1). As a result, glycolysis and oxidative
      phosphorylation are uncoupled, while fatty acid metabolism is altered, leading to
      accumulation of lipid droplets in MTO1 fibroblasts. Unexpectedly, this response
      is different from that triggered by the GTPBP3 defect, as GTPBP3-depleted cells
      exhibit AMPK activation, increased levels of UCP2 and PPARgamma, and inactivation
      of HIF-1. In addition, fatty acid oxidation and respiration are stimulated in
      these cells. Therefore, the HIF-PPARgamma-UCP2-AMPK axis is operating differently
      in MTO1- and GTPBP3-defective cells, which strongly suggests that one of these
      proteins has an additional role, besides mitochondrial-tRNA modification. This
      work provides new and useful information on the molecular basis of the MTO1 and
      GTPBP3 defects and on putative targets for therapeutic intervention.

PMID- 29348688
TI  - Response to correspondence from the ESSA Statement authors.

PMID- 29348689
TI  - Response to "The neurogenic bowel dysfunction score in patients with spinal cord
      injury: methodological issues in reliability and validity".

PMID- 29348690
TI  - The neurogenic bowel dysfunction score in patients with spinal cord injury:
      methodological issues in reliability and validity.

PMID- 29348691
TI  - Correspondence re "Evidence-based scientific exercise guidelines for adults with
      spinal cord injury: an update and new guideline".

PMID- 29348692
TI  - Genome-wide search for higher order epistasis as modifiers of treatment effects
      on bone mineral density in childhood cancer survivors.
AB  - Single-nucleotide polymorphisms (SNPs) contributing to interactions between
      regulatory elements that modulate gene transcription may explain some of the
      uncharacterized variation for complex traits. We explored this hypothesis among
      856 adult survivors of pediatric cancer exposed to curative treatments that
      adversely affect bone mineral density (BMD). To restrict our search to
      interactions among SNPs in regulatory elements, our analysis considered 75523
      SNPs mapped to putative promoter or enhancer regions. In anticipation that power
      to detect higher order epistasis would be low using an exhaustive search and a
      Bonferroni-corrected threshold for genome-wide significance (e.g., P < 5.6 * 10
      14), a novel non-exhaustive statistical algorithm was implemented to detect
      chromosome-wide three-way regulatory interactions. We used a permutation-based
      evaluation statistic to identify candidate SNP interactions with stronger
      associations with BMD than expected. Of the six regulatory 3-SNP interactions
      identified as candidate interactions (P < 3.5 * 10-11) among cancer survivors
      exposed to treatments, five were replicated in an independent cohort of survivors
      (N = 1428) as modifiers of treatment effects on BMD (P < 0.05). Analyses with
      publicly available bioinformatics data revealed that SNPs contributing to
      replicated interactions were enriched for gene expressions (P = 3.6 * 10-4) and
      enhancer states (P < 0.05) in cells relevant for bone biology. For each
      replicated interaction, implicated SNPs were within or directly adjacent to 100
      kb windows of genomic regions that plausibly physically interact in
      lymphoblastoid cells. Our study demonstrates the utility of a hypothesis-driven
      approach in revealing epistasis associated with complex traits.

PMID- 29348694
TI  - Effect of deliberation on the public's attitudes toward consent policies for
      biobank research.
AB  - In this study, we evaluate the effect of education and deliberation on the
      willingness of members of the public to donate tissue to biobank research and on
      their attitudes regarding various biobank consent policies. Participants were
      randomly assigned to a democratic deliberation (DD) group, an education group
      that received only written materials, and a control group. Participants completed
      a survey before the deliberation and two surveys post-deliberation: one on (or
      just after) the deliberation day, and one 4 weeks later. Subjects were asked to
      rate 5 biobank consent policies as acceptable (or not) and to identify the best
      and worst policies. Analyses compared acceptability of different policy options
      and changes in attitudes across the three groups. After deliberation, subjects in
      the DD group were less likely to find broad consent (defined here as consent for
      the use of donations in an unspecified range of future research studies, subject
      to content and process restrictions) and study-by-study consent acceptable. The
      DD group was also significantly less likely to endorse broad consent as the best
      policy (OR = 0.34), and more likely to prefer alternative consent options. These
      results raise ethical challenges to the current widespread reliance on broad
      consent in biobank research, but do not support study-by-study consent.

PMID- 29348693
TI  - Variants in members of the cadherin-catenin complex, CDH1 and CTNND1, cause
      blepharocheilodontic syndrome.
AB  - Blepharocheilodontic syndrome (BCDS) consists of lagophthalmia, ectropion of the
      lower eyelids, distichiasis, euryblepharon, cleft lip/palate and dental anomalies
      and has autosomal dominant inheritance with variable expression. We identified
      heterozygous variants in two genes of the cadherin-catenin complex, CDH1,
      encoding E-cadherin, and CTNND1, encoding p120 catenin delta1 in 15 of 17 BCDS
      index patients, as was recently described in a different publication. CDH1 plays
      an essential role in epithelial cell adherence; CTNND1 binds to CDH1 and controls
      the stability of the complex. Functional experiments in zebrafish and human cells
      showed that the CDH1 variants impair the cell adhesion function of the cadherin
      catenin complex in a dominant-negative manner. Variants in CDH1 have been linked
      to familial hereditary diffuse gastric cancer and invasive lobular breast cancer;
      however, no cases of gastric or breast cancer have been reported in our BCDS
      cases. Functional experiments reported here indicated the BCDS variants comprise
      a distinct class of CDH1 variants. Altogether, we identified the genetic cause of
      BCDS enabling DNA diagnostics and counseling, in addition we describe a novel
      class of dominant negative CDH1 variants.

PMID- 29348695
TI  - Synchronization of Clocks Through 12 km of Strongly Turbulent Air Over a City.
AB  - We demonstrate real-time, femtosecond-level clock synchronization across a low
      lying, strongly turbulent, 12-km horizontal air path by optical two-way time
      transfer. For this long horizontal free-space path, the integrated turbulence
      extends well into the strong turbulence regime corresponding to multiple
      scattering with a Rytov variance up to 7 and with the number of signal
      interruptions exceeding 100 per second. Nevertheless, optical two-way time
      transfer is used to synchronize a remote clock to a master clock with femtosecond
      level agreement and with a relative time deviation dropping as low as a few
      hundred attoseconds. Synchronization is shown for a remote clock based on either
      an optical or microwave oscillator and using either tip-tilt or adaptive-optics
      free-space optical terminals. The performance is unaltered from optical two-way
      time transfer in weak turbulence across short links. These results confirm that
      the two-way reciprocity of the free-space time-of-flight is maintained both under
      strong turbulence and with the use of adaptive optics. The demonstrated
      robustness of optical two-way time transfer against strong turbulence and its
      compatibility with adaptive optics is encouraging for future femtosecond clock
      synchronization over very long distance ground-to-air free-space paths.

PMID- 29348696
TI  - Three-Dimensional Simulations of Tearing and Intermittency in Coronal Jets.
AB  - Observations of coronal jets increasingly suggest that local fragmentation and
      intermittency play an important role in the dynamics of these events. In this
      work we investigate this fragmentation in high-resolution simulations of jets in
      the closed-field corona. We study two realizations of the embedded-bipole model,
      whereby impulsive helical outflows are driven by reconnection between twisted and
      untwisted field across the domed fan plane of a magnetic null. We find that the
      reconnection region fragments following the onset of a tearing-like instability,
      producing multiple magnetic null points and flux-rope structures within the
      current layer. The flux ropes formed within the weak-field region in the center
      of the current layer are associated with "blobs" of density enhancement that
      become filamentary threads as the flux ropes are ejected from the layer,
      whereupon new flux ropes form behind them. This repeated formation and ejection
      of flux ropes provides a natural explanation for the intermittent outflows,
      bright blobs of emission, and filamentary structure observed in some jets.
      Additional observational signatures of this process are discussed. Essentially
      all jet models invoke reconnection between regions of locally closed and locally
      open field as the jet-generation mechanism. Therefore, we suggest that this
      repeated tearing process should occur at the separatrix surface between the two
      flux systems in all jets. A schematic picture of tearing-mediated jet
      reconnection in three dimensions is outlined.

PMID- 29348697
TI  - Optimum Wing Shape Determination of Highly Flexible Morphing Aircraft for
      Improved Flight Performance.
AB  - In this paper, optimum wing bending and torsion deformations are explored for a
      mission adaptive, highly flexible morphing aircraft. The complete highly flexible
      aircraft is modeled using a strain-based geometrically nonlinear beam
      formulation, coupled with unsteady aerodynamics and 6-dof rigid-body motions.
      Since there are no conventional discrete control surfaces for trimming the
      flexible aircraft, the design space for searching the optimum wing geometries is
      enlarged. To achieve high performance flight, the wing geometry is best tailored
      according to the specific flight mission needs. In this study, the steady level
      flight and the coordinated turn flight are considered, and the optimum wing
      deformations with the minimum drag at these flight conditions are searched by
      utilizing a modal-based optimization procedure, subject to the trim and other
      constraints. The numerical study verifies the feasibility of the modal-based
      optimization approach, and shows the resulting optimum wing configuration and its
      sensitivity under different flight profiles.

PMID- 29348698
TI  - Effects of FAME biodiesel and HVORD on emissions from an older-technology diesel
      engine.
AB  - The results of laboratory evaluations were used to compare the potential of two
      alternative, biomass-derived fuels as a control strategy to reduce the exposure
      of underground miners to aerosols and gases emitted by diesel-powered equipment.
      The effects of fatty acid methyl ester (FAME) biodiesel and hydrotreated
      vegetable oil renewable diesel (HVORD) on criteria aerosol and gaseous emissions
      from an older-technology, naturally aspirated, mechanically controlled engine
      equipped with a diesel oxidation catalytic converter were compared with those of
      widely used petroleum-derived, ultralow-sulfur diesels (ULSDs). The emissions
      were characterized for four selected steady-state conditions. When fueled with
      FAME biodiesel and HVORD, the engine emitted less aerosols by total particulate
      mass, total carbon mass, elemental carbon mass and total number than when it was
      fueled with ULSDs. Compared with ULSDs, FAME biodiesel and HVORD produced
      aerosols that were characterized by single modal distributions, smaller count
      median diameters, and lower total and peak concentrations. For the majority of
      test cases, FAME biodiesel and HVORD favorably affected nitric oxide (NO) and
      adversely affected nitrogen dioxide (NO2) generation. Therefore, the use of these
      alternative fuels appears to be a viable tool for the underground mining industry
      to address the issues related to emissions from diesel engines, and to transition
      toward more universal solutions provided by advanced engines with integrated
      exhaust after treatment technologies.

PMID- 29348699
TI  - Industrial Internet of Things: (IIoT) applications in underground coal mines.
AB  - The Industrial Internet of Things (IIoT), a concept that combines sensor networks
      and control systems, has been employed in several industries to improve
      productivity and safety. U.S. National Institute for Occupational Safety and
      Health (NIOSH) researchers are investigating IIoT applications to identify the
      challenges of and potential solutions for transferring IIoT from other industries
      to the mining industry. Specifically, NIOSH has reviewed existing sensors and
      communications network systems used in U.S. underground coal mines to determine
      whether they are capable of supporting IIoT systems. The results show that about
      40 percent of the installed post-accident communication systems as of 2014
      require minimal or no modification to support IIoT applications. NIOSH
      researchers also developed an IIoT monitoring and control prototype system using
      low-cost microcontroller Wi-Fi boards to detect a door opening on a refuge
      alternative, activate fans located inside the Pittsburgh Experimental Mine and
      actuate an alarm beacon on the surface. The results of this feasibility study can
      be used to explore IIoT applications in underground coal mines based on existing
      communication and tracking infrastructure.

PMID- 29348700
TI  - Open-air sprays for capturing and controlling airborne float coal dust on
      longwall faces.
AB  - Float dust deposits in coal mine return airways pose a risk in the event of a
      methane ignition. Controlling airborne dust prior to deposition in the return
      would make current rock dusting practices more effective and reduce the risk of
      coal-dust-fueled explosions. The goal of this U.S. National Institute for
      Occupational Safety and Health study is to determine the potential of open-air
      water sprays to reduce concentrations of airborne float coal dust, smaller than
      75 um in diameter, in longwall face airstreams. This study evaluated unconfined
      water sprays in a featureless tunnel ventilated at a typical longwall face
      velocity of 3.6 m/s (700 fpm). Experiments were conducted for two nozzle
      orientations and two water pressures for hollow cone, full cone, flat fan, air
      atomizing and hydraulic atomizing spray nozzles. Gravimetric samples show that
      airborne float dust removal efficiencies averaged 19.6 percent for all sprays
      under all conditions. The results indicate that the preferred spray nozzle should
      be operated at high fluid pressures to produce smaller droplets and move more
      air. These findings agree with past respirable dust control research, providing
      guidance on spray selection and spray array design in ongoing efforts to control
      airborne float dust over the entire longwall ventilated opening.

PMID- 29348701
TI  - Statistical Significance and the Dichotomization of Evidence: The Relevance of
      the ASA Statement on Statistical Significance and p-values for Statisticians.

PMID- 29348702
TI  - Subjective Cognitive Impairment, Depressive Symptoms, and Fatigue after a TIA or
      Transient Neurological Attack: A Prospective Study.
AB  - Introduction: Subjective cognitive impairment (SCI), depressive symptoms, and
      fatigue are common after stroke and are associated with reduced quality of life.
      We prospectively investigated their prevalence and course after a transient
      ischemic attack (TIA) or nonfocal transient neurological attack (TNA) and the
      association with diffusion-weighted imaging (DWI) lesions. Methods: The Cognitive
      Failures Questionnaire, Hospital Anxiety and Depression Scale, and Subjective
      Fatigue subscale from the Checklist Individual Strength were used to assess
      subjective complaints shortly after TIA or TNA and six months later. With
      repeated measure analysis, the associations between DWI lesion presence or
      clinical diagnosis (TIA or TNA) and subjective complaints over time were
      determined. Results: We included 103 patients (28 DWI positive). At baseline, SCI
      and fatigue were less severe in DWI positive than in DWI negative patients,
      whereas at follow-up, there were no differences. SCI (p = 0.02) and fatigue (p =
      0.01) increased in severity only in DWI positive patients. There were no
      differences between TIA and TNA. Conclusions: Subjective complaints are highly
      prevalent in TIA and TNA patients. The short-term prognosis is not different
      between DWI-positive and DWI negative patients, but SCI and fatigue increase in
      severity within six months after the event when an initial DWI lesion is present.

PMID- 29348703
TI  - Platelet-Released Growth Factors Modulate the Secretion of Cytokines in
      Synoviocytes under Inflammatory Joint Disease.
AB  - The etiology and pathogenesis of rheumatoid arthritis (RA) are marked by a
      complex interplay of various cell populations and is mediated by different
      signaling pathways. Traditionally, therapies have primarily focused on pain
      relief, reducing inflammation and the recovery of joint function. More recently,
      however, researchers have discussed the therapeutic efficacy of autologous
      platelet-rich plasma (PRP). The main objective of this work is to examine the
      influences of platelet-released growth factor (PRGF) on human synoviocytes under
      inflammatory conditions. Additionally, it is checked to which extend treatment
      with platelet concentrate influences the release of cytokines form synoviocytes.
      For this purpose, an in vitro RA model was created by stimulating the cells with
      the TNF-alpha. The release of cytokines was measured by ELISA. The cytokine gene
      expression was analyzed by real-time PCR. It has been observed that the
      stimulation concentration of 10 ng/ml TNF-alpha resulted in a significantly
      increased endogenous secretion and gene expression of IL-6 and TNF-alpha. The
      anti-inflammatory effect of PRGF could be confirmed through significant reduction
      of TNF-alpha and IL-1beta. An induced inflammatory condition seems to cause PRGF
      to inhibit the release of proinflammatory cytokines. Further study is required to
      understand the exact effect mechanism of PRGF on synoviocytes.

PMID- 29348705
TI  - Proximal extrapolated gradient methods for variational inequalities.
AB  - The paper concerns with novel first-order methods for monotone variational
      inequalities. They use a very simple linesearch procedure that takes into account
      a local information of the operator. Also, the methods do not require Lipschitz
      continuity of the operator and the linesearch procedure uses only values of the
      operator. Moreover, when the operator is affine our linesearch becomes very
      simple, namely, it needs only simple vector-vector operations. For all our
      methods, we establish the ergodic convergence rate. In addition, we modify one of
      the proposed methods for the case of a composite minimization. Preliminary
      results from numerical experiments are quite promising.

PMID- 29348704
TI  - Stimulation of Alpha7 Nicotinic Acetylcholine Receptor Attenuates Nicotine
      Induced Upregulation of MMP, MCP-1, and RANTES through Modulating ERK1/2/AP-1
      Signaling Pathway in RAW264.7 and MOVAS Cells.
AB  - Vagus nerve stimulation through alpha7 nicotine acetylcholine receptors (alpha7
      nAChR) signaling had been demonstrated attenuation of inflammation. This study
      aimed to determine whether PNU-282987, a selective alpha7-nAChR agonist, affected
      activities of matrix metalloproteinase (MMP) and inflammatory cytokines in
      nicotine-treatment RAW264.7 and MOVAS cells and to assess the underlying
      molecular mechanisms. RAW264.7 and MOVAS cells were treated with nicotine at
      different concentrations (0, 1, 10, and 100 ng/ml) for 0-120 min. Nicotine
      markedly stimulated the phosphorylation of extracellular signal-regulated
      kinase1/2 (ERK1/2) and c-Jun in RAW264.7 cells. Pretreatment with U0126
      significantly suppressed phosphorylation of ERK1/2 and further attenuated
      nicotine-induced activation of c-Jun and upregulation of MMP-2, MMP-9, monocyte
      chemotactic protein- (MCP-) 1, and regulated upon activation normal T cell
      expressed and secreted (RANTES). Similarly, nicotine treatment also increased
      phosphorylation of c-Jun and expressions of MMP-2, MMP-9, MCP-1, and RANTES in
      MOVAS cells. When cells were pretreated with PNU-282987, nicotine-induced
      activations of ERK1/2 and c-Jun in RAW264.7 cells and c-Jun in MOVAS cells were
      effectively inhibited. Furthermore, nicotine-induced secretions of MMP-2, MMP-9,
      MCP-1, and RANTES were remarkably downregulated. Treatment with alpha7-nAChR
      agonist inhibits nicotine-induced upregulation of MMP and inflammatory cytokines
      through modulating ERK1/2/AP-1 signaling in RAW264.7 cells and AP-1 in MOVAS
      cells, providing a new therapeutic for abdominal aortic aneurysm.

PMID- 29348706
TI  - Diagnosis and Treatment of Clostridium difficile Infection (CDI).
AB  - Early and accurate diagnosis is essential for optimal treatment of individuals
      with Clostridium difficile infection (CDI) and for implementation of effective
      infection control procedures. The decision about which diagnostic test to use is
      an important one that should be based on test sensitivity, specificity, and
      predictive value. The challenges of CDI go beyond rapid identification and
      management of symptomatic patients. Asymptomatic carriage has long been suspected
      in C. difficile transmission, but it may play a larger role than previously
      thought. Emerging information also shows that patients treated for CDI remain
      colonized for many weeks after symptom resolution. In fact, stool culture
      positivity increases during the first weeks following treatment completion.
      Treatments that reduce the duration and degree of asymptomatic shedding could
      have added benefit for reduced transmission.

PMID- 29348707
TI  - Evolution of Knowledge, Awareness, and Practices regarding Zika Virus from 2016
      to 2017.
AB  - Objective: Our team created a knowledge, attitudes, and practice (KAP) survey in
      order to assess changes over time in healthcare provider and community member
      awareness of Zika virus symptoms, transmission, treatment, and current and future
      concerns. Study Design: The cross-sectional survey was issued at an academic
      medical center in Washington, DC, and via an online link to healthcare providers
      and community members between June and August 2016. Survey distribution was then
      repeated the following year, from March to April 2017. Outcomes were compared by
      survey year and healthcare provider versus community member status using SAS
      Program Version 9.4. Results: Significant differences in knowledge, attitudes,
      and practices existed between 2016 and 2017 survey time points. By 2017, more
      respondents had knowledge of various Zika virus infection characteristics;
      however healthcare provider knowledge also waned in certain areas. Attitudes
      towards Zika virus infection displayed an overall decreased concern by 2017.
      Practice trends by 2017 demonstrated fewer travel restrictions to Zika-endemic
      areas and increased mosquito protective measures within the US. Conclusions: Our
      results provide novel insight into the transformation of knowledge, attitudes,
      and practice of community members and healthcare providers regarding Zika virus
      since its declaration as a public health emergency of international concern in
      2016.

PMID- 29348708
TI  - HybPhyloMaker: Target Enrichment Data Analysis From Raw Reads to Species Trees.
AB  - Summary: Hybridization-based target enrichment in combination with genome
      skimming (Hyb-Seq) is becoming a standard method of phylogenomics. We developed
      HybPhyloMaker, a bioinformatics pipeline that performs target enrichment data
      analysis from raw reads to supermatrix-, supertree-, and multispecies coalescent
      based species tree reconstruction. HybPhyloMaker is written in BASH and
      integrates common bioinformatics tools. It can be launched both locally and on a
      high-performance computer cluster. Compared with existing target enrichment data
      analysis pipelines, HybPhyloMaker offers the following main advantages:
      implementation of all steps of data analysis from raw reads to species tree
      reconstruction, calculation and summary of alignment and gene tree properties
      that assist the user in the selection of "quality-filtered" genes, implementation
      of several species tree reconstruction methods, and analysis of the coding
      regions of organellar genomes. Availability: The HybPhyloMaker scripts, manual as
      well as a test data set, are available in https://github.com/tomas
      fer/HybPhyloMaker/. HybPhyloMaker is licensed under open-source license GPL v.3
      allowing further modifications.

PMID- 29348709
TI  - Perioperative Medicine: A Burgeoning Field with Profound Importance to a Modern
      Clinician.
AB  - AIMS AND SCOPE This article serves in introducing the readers to the developing
      field of perioperative medicine. We have made an effort to come up with the
      latest management guidelines covering multiple subspecialties in form of a
      special supplement. This compendium in perioperative medicine serves as a
      comprehensive guide to a practicing clinician, in managing patients with various
      medical comorbidities undergoing surgical procedures and avoiding common
      pitfalls.

PMID- 29348711
TI  - Efficacy of Empirical Therapy With Combined Ciprofloxacin Versus Topical Drops
      Alone in Patients With Tubotympanic Chronic Suppurative Otitis Media: A
      Randomized Double-Blind Controlled Trial.
AB  - Background: One of the prevailing otologic infections in our country is chronic
      suppurative otitis media, especially the tubotympanic type for which various
      treatment protocols are followed. Usually, oral and topical antibiotics (mainly
      quinolones) are given alone or in combination. There is a lack of consensus as to
      whether topical drops alone are effective or a combined oral and systemic therapy
      should be prescribed. In our study, we have attempted to observe the efficacy of
      empirical therapy with combined ciprofloxacin versus topical drops only in
      patients with tubotympanic chronic suppurative otitis media for control of
      infection. Methodology: A total of 100 patients visiting the outpatient ENT
      department at our tertiary care hospital with clinically diagnosed chronic
      suppurative otitis media (tubotympanic type) were enrolled in our study. The
      study was reviewed and accepted by the ethical review committee. A detailed
      proforma was filled for all patients. All patients after aural toilet were
      subjected randomly to one of the 2 treatment methods, ie, topical ciprofloxacin
      ear drops plus an oral placebo or combined oral and topical ciprofloxacin. These
      patients were reviewed after 1 week of treatment. Results: It was observed that
      48 of 50 (96%) patients responded to treatment in the group receiving topical
      ciprofloxacin, whereas 49 of 50 (98%) patients responded in the group receiving
      combined therapy. This difference was not significant. Moreover, age, sex, and
      duration of discharge did not have any effect on treatment. There were minimal
      side effects in both groups, which were also not significant and disappeared
      after discontinuation of treatment. Conclusions: The results of this study show
      that topical ciprofloxacin drops were as effective as combined oral and topical
      ciprofloxacin and that the addition of oral drug did not have any beneficial
      effect and added only to the cost of treatment.

PMID- 29348710
TI  - The Protein Tyrosine Phosphatase Nonreceptor 22 (PTPN22) R620W Functional
      Polymorphism in Psoriasis.
AB  - Background: Psoriasis is a complex autoimmune disease caused by the interaction
      of genetic and environmental factors. PTPN22 gene polymorphism has been reported
      to affect psoriasis susceptibility; however, no data are available for Middle
      Eastern populations. Objective: The aim of this study was to investigate the
      association of PTPN22 (1858C/T) R620W polymorphism with psoriasis in a Saudi
      cohort. Methods: Saudi subjects (n = 306) including patients with psoriasis (n =
      106) and matched controls (n = 200) were studied for PTPN22 variants using tetra
      primer amplification refractory mutation system-polymerase chain reaction method.
      The frequencies of alleles and genotypes of PTPN22 (1858C/T) polymorphism were
      compared between patients and controls. Results: The frequency of CT genotype of
      PTPN22 (1858C/T) polymorphism was significantly higher, whereas that of CC
      genotype was lower in patients with psoriasis than in controls (P < .001,
      relative risk [RR] = 7.151). The homozygous genotype TT was absent in both the
      patients and healthy controls. The frequency of allele T encoding tryptophan (W)
      was significantly increased (P < .001, RR = 5.76), whereas that of allele C
      encoding arginine (R) decreased in psoriasis cases as compared with controls (P <
      .001, RR = 0.173) indicating that individuals carrying allele T are more
      susceptible to psoriasis than noncarriers. Conclusions: PTPN22 (1858C/T)
      polymorphism is positively associated with susceptibility of psoriasis in Saudis
      and can be developed as biomarker for evaluating psoriasis risk. However, further
      studies on PTPN22 polymorphism in larger samples from different geographical
      areas and ethnicity are warranted.

PMID- 29348712
TI  - Assessment of Ramadan Education and Knowledge Among Diabetic Patients.
AB  - Background: During Ramadan, Muslims fast from dawn until dusk for one lunar month
      every year. Most of the Muslim patients with diabetes are unaware of the
      potential complications that can occur while fasting, such as hypoglycemia. The
      aim of this study is to assess the the patient education level and patients'
      overall awareness of any possible complications that could occur while fasting
      during Ramadan and to determine how these patients deal with these complications.
      Methods: We conducted a cross-sectional study and surveyed diabetic patients
      about their diabetes-related knowledge over a period of 4 months from the
      outpatient clinic at the Obesity, Endocrine, and Metabolism Center at King Fahad
      Medical City. Patients were included if they were >=16 years and if they had been
      receiving treatment for at least 1 year before the study, irrespective of the
      medications used; patients were also asked about the presence or absence of
      complications. Results: This study included 477 patients (325 women and 152 men).
      Most patients (297; 62.3%) had type 2 diabetes. The patients' mean age was 39.72
      +/- 15.29 years, and the mean duration of diabetes was 10.80 +/- 5.88 years.
      During the preceding Ramadan, 76% of patients reported fasting, whereas 58% said
      that they monitored their blood glucose levels once per day. Hypoglycemic
      episodes were reported in 60.3% of cases with type 2 diabetes and in 8.3% of
      cases with type 1 diabetes. Among those who had hypoglycemia, 2.8% of patients
      with type 1 diabetes and 17.8% with type 2 diabetes broke their fast. Finally,
      54% of patients reported that their health care providers offered them
      instructions on diabetes management during Ramadan. Conclusions: Ramadan health
      education in diabetes can encourage, improve, and guide patients to change their
      lifestyles during Ramadan while minimizing the risk of acute complications.

PMID- 29348713
TI  - Disentangling the Sleep-Pain Relationship in Pediatric Chronic Pain: The
      Mediating Role of Internalizing Mental Health Symptoms.
AB  - Background: Pediatric chronic pain often emerges in adolescence and cooccurs with
      internalizing mental health issues and sleep impairments. Emerging evidence
      suggests that sleep problems may precede the onset of chronic pain as well as
      anxiety and depression. Studies conducted in pediatric populations with pain
      related chronic illnesses suggest that internalizing mental health symptoms may
      mediate the sleep-pain relationship; however, this has not been examined in youth
      with primary pain disorders. Objective: To examine whether anxiety and depressive
      symptoms mediated relationships between sleep quality and pain outcomes among
      youth with chronic pain. Methods: Participants included 147 youth (66.7% female)
      aged 8-18 years who were referred to a tertiary-level chronic pain program. At
      intake, the youth completed psychometrically sound measures of sleep quality,
      pain intensity, pain interference, and anxiety and depressive symptoms. Results:
      As hypothesized, poor sleep quality was associated with increased pain intensity
      and pain interference, and anxiety and depressive symptoms mediated these sleep
      pain relationships. Discussion: For youth with chronic pain, poor sleep quality
      may worsen pain through alterations in mood and anxiety; however, prospective
      research using objective measures is needed. Future research should examine
      whether targeting sleep and internalizing mental health symptoms in treatments
      improve pain outcomes in these youth.

PMID- 29348714
TI  - Orofacial Pains.

PMID- 29348715
TI  - Ginseng and obesity.
AB  - Although ginseng has been shown to have an antiobesity effect, antiobesity
      related mechanisms are complex and have not been completely elucidated. In the
      present study, we evaluated ginseng's effects on food intake, the digestion, and
      absorption systems, as well as liver, adipose tissue, and skeletal muscle in
      order to identify the mechanisms involved. A review of previous in vitro and in
      vivo studies revealed that ginseng and ginsenosides can increase energy
      expenditure by stimulating the adenosine monophosphate-activated kinase pathway
      and can reduce energy intake. Moreover, in high fat diet-induced obese and
      diabetic individuals, ginseng has shown a two-way adjustment effect on
      adipogenesis. Nevertheless, most of the previous studies into antiobesity effects
      of ginseng have been animal based, and there is a paucity of evidence supporting
      the suggestion that ginseng can exert an antiobesity effect in humans.

PMID- 29348716
TI  - Cylindrocarpon destructans/Ilyonectria radicicola-species complex: Causative
      agent of ginseng root-rot disease and rusty symptoms.
AB  - Cylindrocarpon destructans/Ilyonectria radicicola is thought to cause both rusty
      symptom and root-rot disease of American and Korean ginseng. Root-rot disease
      poses a more serious threat to ginseng roots than rusty symptoms, which we argue
      result from the plant defense response to pathogen attack. Therefore, strains
      causing rotten root are characterized as more aggressive than strains causing
      rusty symptoms. In this review, we state 1- the molecular evidence indicating
      that the root-rot causing strains are genetically distinct considering them as a
      separate species of Ilyonectria, namely I. mors-panacis and 2- the physiological
      and biochemical differences between the weakly and highly aggressive species as
      well as those between rusty and rotten ginseng plants. Eventually, we postulated
      that rusty symptom occurs on ginseng roots due to incompatible interactions with
      the weakly aggressive species of Ilyonectria, by the established iron-phenolic
      compound complexes while root-rot is developed by I. mors-panacis infection due
      to the production of high quantities of hydrolytic and oxidative fungal enzymes
      which destroy the plant defensive barriers, in parallel with the pathogen growth
      stimulation by utilizing the available iron. Furthermore, we highlight future
      areas for study that will help elucidate the complete mechanism of root-rot
      disease development.

PMID- 29348717
TI  - High-performance liquid chromatography analysis of phytosterols in Panax ginseng
      root grown under different conditions.
AB  - Background: The Panax ginseng plant is used as an herbal medicine. Phytosterols
      of P. ginseng have inhibitory effects on inflammation-related factors in HepG2
      cells. Methods: Phytosterols (e.g., stigmasterol and beta-sitosterol) in the
      roots of P. ginseng grown under various conditions were analyzed using high
      performance liquid chromatography. The P. ginseng roots analyzed in this study
      were collected from three cultivation areas in Korea (i.e., Geumsan, Yeongju, and
      Jinan) and differed by cultivation year (i.e., 4 years, 5 years, and 6 years) and
      production process (i.e., straight ginseng, red ginseng, and white ginseng).
      Results: The concentrations of stigmasterol and beta-sitosterol in P. ginseng
      roots were 2.22-23.04 mg/g and 7.35-59.09 mg/g, respectively. The highest
      concentrations of stigmasterol and beta-sitosterol were in the roots of 6-year
      old P. ginseng cultivated in Jinan (82.14 mg/g and 53.23 mg/g, respectively).
      Conclusion: Six-year-old white ginseng and white ginseng cultivated in Jinan
      containing stigmasterol and beta-sitosterol are potentially a new source of
      income in agriculture.

PMID- 29348718
TI  - Qualitative and quantitative analysis of furosine in fresh and processed
      ginsengs.
AB  - Background: Furosine (E-N-2-furoylmethyl-L-lysine, FML) is an amino acid
      derivative, which is considered to be an important indicator of the extent of
      damage (deteriorating the quality of amino acid and proteins due to a blockage of
      lysine and a decrease in the digestibility of proteins) during the early stages
      of the Maillard reaction. In addition, FML has been proven to be harmful because
      it is closely related to a variety of diseases such as diabetes. The qualitative
      analysis of FML in fresh and processed ginsengs was confirmed using HPLC-MS.
      Methods: An ion-pair reversed-phase LC method was used for the quantitative
      analysis of FML in various ginseng samples. Results: The contents of FML in the
      ginseng samples were 3.35-42.28 g/kg protein. The lowest value was observed in
      the freshly collected ginseng samples, and the highest value was found in the
      black ginseng concentrate. Heat treatment and honey addition significantly
      increased the FML content from 3.35 g/kg protein to 42.28 g/kg protein.
      Conclusion: These results indicate that FML is a promising indicator to estimate
      the heat treatment degree and honey addition level during the manufacture of
      ginseng products. The FML content is also an important parameter to identity the
      quality of ginseng products. In addition, the generation and regulation of
      potentially harmful Maillard reaction products-FML in ginseng processing was also
      investigated, providing a solid theoretical foundation and valuable reference for
      safe ginseng processing.

PMID- 29348719
TI  - Effects of processing method on the pharmacokinetics and tissue distribution of
      orally administered ginseng.
AB  - Background: The use of different methods for the processing of ginseng can result
      in alterations in its medicinal properties and efficacy. White ginseng (WG),
      frozen ginseng (FG), and red ginseng (RG) are produced using different methods.
      WG, FG, and RG possess different pharmacological properties. Methods: WG, FG, and
      RG extracts and pure ginsenosides were administered to rats to study the
      pharmacokinetics and tissue distribution characteristics of the following
      ginsenosides-Rg1, Re, Rb1, and Rd. The concentrations of the ginsenosides in the
      plasma and tissues were determined using UPLC-MS/MS. Results: The rate and extent
      of absorption of Rg1, Re, Rb1, and Rd appeared to be affected by the different
      methods used in processing the ginseng samples. The areas under the plasma drug
      concentration-time curves (AUCs) of Rg1, Re, Rb1, and Rd were significantly
      higher than those of the pure ginsenosides. In addition, the AUCs of Rg1, Re,
      Rb1, and Rd were different for WG, FG, and RG. The amounts of Rg1, Re, Rd, and
      Rb1 were significantly (p < 0.05) higher in the tissues than those of the pure
      ginsenosides. The amounts of Re, Rb1, and Rd from the RG extract were
      significantly higher than those from the WG and FG extracts in the heart, lungs,
      and kidneys of the rats. Conclusion: Our results show that the use of different
      methods to process ginseng might affect the pharmacokinetics and oral
      bioavailability of ginseng as well as the tissue concentrations of Rg1, Re, Rd,
      and Rb1.

PMID- 29348720
TI  - Gintonin absorption in intestinal model systems.
AB  - Background: Recently, we identified a novel ginseng-derived lysophosphatidic acid
      receptor ligand, called gintonin. We showed that gintonin induces [Ca2+]i
      transient-mediated morphological changes, proliferation, and migration in cells
      expressing lysophosphatidic acid receptors and that oral administration of
      gintonin exhibits anti-Alzheimer disease effects in model mice. However, little
      is known about the intestinal absorption of gintonin. The aim of this study was
      to investigate gintonin absorption using two model systems. Methods: Gintonin
      membrane permeation was examined using a parallel artificial membrane permeation
      assay, and gintonin absorption was evaluated in a mouse everted intestinal sac
      model. Results: The parallel artificial membrane permeation assay showed that
      gintonin could permeate an artificial membrane in a dose-dependent manner. In the
      everted sac model, gintonin absorption increased with incubation time (from 0 min
      to 60 min), followed by a decrease in absorption. Gintonin absorption into
      everted sacs was also dose dependent, with a nonlinear correlation between
      gintonin absorption and concentration at 0.1-3 mg/mL and saturation at 3-5 mg/mL.
      Gintonin absorption was inhibited by the Rho kinase inhibitor Y-27632 and the
      sodium-glucose transporter inhibitor phloridzin. Moreover, lipid extraction with
      methanol also attenuated gintonin absorption, suggesting the importance of the
      lipid portion of gintonin in absorption. This result shows that gintonin might be
      absorbed through passive diffusion, paracellular, and active transport pathways.
      Conclusion: The present study shows that gintonin could be absorbed in the
      intestine through transcellular and paracellular diffusion, and active transport.
      In addition, the lipid component of gintonin might play a key role in its
      intestinal absorption.

PMID- 29348721
TI  - Rare ginsenoside Ia synthesized from F1 by cloning and overexpression of the UDP
      glycosyltransferase gene from Bacillus subtilis: synthesis, characterization, and
      in vitro melanogenesis inhibition activity in BL6B16 cells.
AB  - Background: Ginsenoside F1 has been described to possess skin-whitening effects
      on humans. We aimed to synthesize a new ginsenoside derivative from F1 and
      investigate its cytotoxicity and melanogenesis inhibitory activity in B16BL6
      cells using recombinant glycosyltransferase enzyme. Glycosylation has the
      advantage of synthesizing rare chemical compounds from common compounds with
      great ease. Methods: UDP-glycosyltransferase (BSGT1) gene from Bacillus subtilis
      was selected for cloning. The recombinant glycosyltransferase enzyme was
      purified, characterized, and utilized to enzymatically transform F1 into its
      derivative. The new product was characterized by NMR techniques and evaluated by
      MTT, melanin count, and tyrosinase inhibition assay. Results: The new derivative
      was identified as (20S)-3beta,6alpha,12beta,20-tetrahydroxydammar-24-ene-20-O
      beta-D-glucopyranosyl-3-O-beta-D-glucopyranoside (ginsenoside Ia), which
      possesses an additional glucose linked into the C-3 position of substrate F1. Ia
      had been previously reported; however, no in vitro biological activity was
      further examined. This study focused on the mass production of arduous
      ginsenoside Ia from accessible F1 and its inhibitory effect of melanogenesis in
      B16BL6 cells. Ia showed greater inhibition of melanin and tyrosinase at 100
      MUmol/L than F1 and arbutin. These results suggested that Ia decreased cellular
      melanin synthesis in B16BL6 cells through downregulation of tyrosinase activity.
      Conclusion: To our knowledge, this is the first study to report on the mass
      production of rare ginsenoside Ia from F1 using recombinant UDP
      glycosyltransferase isolated from B. subtillis and its superior melanogenesis
      inhibitory activity in B16BL6 cells as compared to its precursor. In brief,
      ginsenoside Ia can be applied for further study in cosmetics.

PMID- 29348722
TI  - Regulatory effects of saponins from Panax japonicus on colonic epithelial tight
      junctions in aging rats.
AB  - Background: Saponins from Panax japonicus (SPJ) are the most abundant and main
      active components of P. japonicus, which replaces ginseng roots in treatment for
      many kinds of diseases in the minority ethnic group in China. Our previous
      studies have demonstrated that SPJ has the effects of anti-inflammation through
      the mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF
      kappaB) signaling pathways. The present study was designed to investigate whether
      SPJ can modulate intestinal tight junction barrier in aging rats and further to
      explore the potential mechanism. Methods: Aging rats had been treated with
      different doses (10 mg/kg, 30 mg/kg, and 60 mg/kg) of SPJ for 6 mo since they
      were 18 mo old. After the rats were euthanized, the colonic samples were
      harvested. Levels of tight junctions (claudin-1 and occludin) were determined by
      immunohistochemical staining. Levels of proinflammatory cytokines (interleukin
      1beta and tumor necrosis factor-alpha) were examined by Western blot. NF-kappaB
      and phosphorylation of MAPK signaling pathways were also determined by Western
      blot. Results: We found that SPJ increased the expression of the tight junction
      proteins claudin-1 and occludin in the colon of aging rats. Treatment with SPJ
      decreased the levels of interleukin-1beta and tumor necrosis factor-alpha,
      reduced the phosphorylation of three MAPK isoforms, and inhibited the expression
      of NF-kappaB in the colon of aging rats. Conclusion: The studies demonstrated
      that SPJ modulates the damage of intestinal epithelial tight junction in aging
      rats, inhibits inflammation, and downregulates the phosphorylation of the MAPK
      and NF-kappaB signaling pathways.

PMID- 29348723
TI  - Metabolite profiling of fermented ginseng extracts by gas chromatography mass
      spectrometry.
AB  - Background: Ginseng contains many small metabolites such as amino acids, fatty
      acids, carbohydrates, and ginsenosides. However, little is known about the
      relationships between microorganisms and metabolites during the entire ginseng
      fermentation process. We investigated metabolic changes during ginseng
      fermentation according to the inoculation of food-compatible microorganisms.
      Methods: Gas chromatography mass spectrometry (GC-MS) datasets coupled with the
      multivariate statistical method for the purpose of latent-information extraction
      and sample classification were used for the evaluation of ginseng fermentation.
      Four different starter cultures (Saccharomyces bayanus, Bacillus subtilis,
      Lactobacillus plantarum, and Leuconostoc mesenteroide) were used for the ginseng
      extract fermentation. Results: The principal component analysis score plot and
      heat map showed a clear separation between ginseng extracts fermented with S.
      bayanus and other strains. The highest levels of fructose, maltose, and galactose
      in the ginseng extracts were found in ginseng extracts fermented with B.
      subtilis. The levels of succinic acid and malic acid in the ginseng extract
      fermented with S. bayanus as well as the levels of lactic acid, malonic acid, and
      hydroxypruvic acid in the ginseng extract fermented with lactic acid bacteria (L.
      plantarum and L. mesenteroide) were the highest. In the results of taste features
      analysis using an electronic tongue, the ginseng extracts fermented with lactic
      acid bacteria were significantly distinguished from other groups by a high index
      of sour taste probably due to high lactic acid contents. Conclusion: These
      results suggest that a metabolomics approach based on GC-MS can be a useful tool
      to understand ginseng fermentation and evaluate the fermentative characteristics
      of starter cultures.

PMID- 29348724
TI  - Ginsenoside Rg3 promotes inflammation resolution through M2 macrophage
      polarization.
AB  - Background: Ginsenosides have been reported to have many health benefits,
      including anti-inflammatory effects, and the resolution of inflammation is now
      considered to be an active process driven by M2-type macrophages. In order to
      determine whether ginsenosides modulate macrophage phenotypes to reduce
      inflammation, 11 ginsenosides were studied with respect to macrophage
      polarization and the resolution of inflammation. Methods: Mouse peritoneal
      macrophages were polarized into M1 or M2 phenotypes. Reverse transcription
      polymerase chain reaction, Western blotting, and measurement of nitric oxide (NO)
      and prostaglandin E2 levels were performed in vitro and in a zymosan-induced
      peritonitis C57BL/6 mouse model. Results: Ginsenoside Rg3 was identified as a
      proresolving ginseng compound based on the induction of M2 macrophage
      polarization. Ginsenoside Rg3 not only induced the expression of arginase-1 (a
      representative M2 marker gene), but also suppressed M1 marker genes, such as
      inducible NO synthase, and NO levels. The proresolving activity of ginsenoside
      Rg3 was also observed in vivo in a zymosan-induced peritonitis model. Ginsenoside
      Rg3 accelerated the resolution process when administered at peak inflammatory
      response into the peritoneal cavity. Conclusion: These results suggest that
      ginsenoside Rg3 induces the M2 polarization of macrophages and accelerates the
      resolution of inflammation. This finding opens a new avenue in ginseng
      pharmacology.

PMID- 29348725
TI  - Protective effect of ginsenoside Rb1 against tacrolimus-induced apoptosis in
      renal proximal tubular LLC-PK1 cells.
AB  - Background: The aim of the present study was to evaluate the potential protective
      effects of six ginsenosides (Rb1, Rb2, Rc, Rd, Rg1, and Rg3) isolated from Panax
      ginseng against tacrolimus (FK506)-induced apoptosis in renal proximal tubular
      LLC-PK1 cells. Methods: LLC-PK1 cells were treated with FK506 and ginsenosides,
      and cell viability was measured. Protein expressions of mitogen-activated protein
      kinases, caspase-3, and kidney injury molecule-1 (KIM-1) were evaluated by
      Western blotting analyses. The number of apoptotic cells was measured using an
      image-based cytometric assay. Results: Reduction in cell viability by 60MUM FK506
      was ameliorated significantly by cotreatment with ginsenosides Rg1 and Rb1. The
      phosphorylation of p38, extracellular signal-regulated kinases, and KIM-1, and
      cleavage of caspase-3, increased markedly in LLC-PK1 cells treated with FK506 and
      significantly decreased after cotreatment with ginsenoside Rb1. The number of
      apoptotic cells decreased by 6.0% after cotreatment with ginsenoside Rb1 (10MUM
      and 50MUM). Conclusion: The antiapoptotic effects of ginsenoside Rb1 on FK506
      induced apoptosis were mediated by the inhibition of mitogen-activated protein
      kinases and caspase activation.

PMID- 29348726
TI  - Photoaging protective effects of BIOGF1K, a compound-K-rich fraction prepared
      from Panax ginseng.
AB  - Background: BIOGF1K, a compound-K-rich fraction, has been shown to display anti
      inflammatory activity. Although Panax ginseng is widely used for the prevention
      of photoaging events induced by UVB irradiation, the effect of BIOGF1K on
      photoaging has not yet been examined. In this study, we investigated the effects
      of BIOGF1K on UVB-induced photoaging events. Methods: We analyzed the ability of
      BIOGF1K to prevent UVB-induced apoptosis, enhance matrix metalloproteinase (MMP)
      expression, upregulate anti-inflammatory activity, reduce sirtuin 1 expression,
      and melanin production using reverse transcription-polymerase chain reaction,
      melanin content assay, tyrosinase assay, and flow cytometry. We also evaluated
      the effects of BIOGF1K on the activator protein-1 signaling pathway, which plays
      an important role in photoaging, by immunoblot analysis and luciferase reporter
      gene assays. Results: Treatment of UVB-irradiated NIH3T3 fibroblasts with BIOGF1K
      prevented UVB-induced cell death, inhibited apoptosis, suppressed morphological
      changes, reduced melanin secretion, restored the levels of type I procollagen and
      sirtuin 1, and prevented mRNA upregulation of MMP-1, MMP-2, and cyclo-oxygenase
      2; these effects all occurred in a dose-dependent manner. In addition, BIOGF1K
      markedly reduced activator-protein-1-mediated luciferase activity and decreased
      the activity of mitogen-activated protein kinases (extracellular response kinase,
      p38, and C-Jun N-terminal kinase). Conclusion: Our results strongly suggest that
      BIOGF1K has anti-photoaging activity and that BIOGF1K could be used in anti-aging
      cosmeceutical preparations.

PMID- 29348727
TI  - Efficacy and safety of Panax ginseng berry extract on glycemic control: A 12-wk
      randomized, double-blind, and placebo-controlled clinical trial.
AB  - Background: Antihyperglycemic effects of Panax ginseng berry have never been
      explored in humans. The aims of this study were to assess the efficacy and safety
      of a 12-wk treatment with ginseng berry extract in participants with a fasting
      glucose level between 100 mg/dL and 140 mg/dL. Methods: This study was a 12-wk,
      randomized, double-blind, placebo-controlled clinical trial. A total of 72
      participants were randomly allocated to two groups of either ginseng berry
      extract or placebo, and 63 participants completed the study. The parameters
      related to glucose metabolism were assessed. Results: Although the present study
      failed to show significant antihyperglycemic effects of ginseng berry extract on
      the parameters related to blood glucose and lipid metabolism in the total study
      population, it demonstrated that ginseng berry extract could significantly
      decrease serum concentration of fasting glucose by 3.7% (p = 0.035), postprandial
      glucose at 60 min during 75 g oral glucose tolerance test by 10.7% (p = 0.006),
      and the area under the curve for glucose by 7.7% (p = 0.024) in those with
      fasting glucose level of 110 mg/dL or higher, while the placebo group did not
      exhibit a statistically significant decrease. Safety profiles were not different
      between the two groups. Conclusion: The present study suggests that ginseng berry
      extract has the potential to improve glucose metabolism in human, especially in
      those with fasting glucose level of 110 mg/dL or higher. For a more meaningful
      benefit, further research in people with higher blood glucose levels is required.

PMID- 29348728
TI  - Systems-level mechanisms of action of Panax ginseng: a network pharmacological
      approach.
AB  - Panax ginseng has been used since ancient times based on the traditional Asian
      medicine theory and clinical experiences, and currently, is one of the most
      popular herbs in the world. To date, most of the studies concerning P. ginseng
      have focused on specific mechanisms of action of individual constituents.
      However, in spite of many studies on the molecular mechanisms of P. ginseng, it
      still remains unclear how multiple active ingredients of P. ginseng interact with
      multiple targets simultaneously, giving the multidimensional effects on various
      conditions and diseases. In order to decipher the systems-level mechanism of
      multiple ingredients of P. ginseng, a novel approach is needed beyond
      conventional reductive analysis. We aim to review the systems-level mechanism of
      P. ginseng by adopting novel analytical framework-network pharmacology. Here, we
      constructed a compound-target network of P. ginseng using experimentally
      validated and machine learning-based prediction results. The targets of the
      network were analyzed in terms of related biological process, pathways, and
      diseases. The majority of targets were found to be related with primary metabolic
      process, signal transduction, nitrogen compound metabolic process, blood
      circulation, immune system process, cell-cell signaling, biosynthetic process,
      and neurological system process. In pathway enrichment analysis of targets,
      mainly the terms related with neural activity showed significant enrichment and
      formed a cluster. Finally, relative degrees analysis for the target-disease
      association of P. ginseng revealed several categories of related diseases,
      including respiratory, psychiatric, and cardiovascular diseases.

PMID- 29348729
TI  - Panax ginseng exerts antidepressant-like effects by suppressing neuroinflammatory
      response and upregulating nuclear factor erythroid 2 related factor 2 signaling
      in the amygdala.
AB  - Background: Depression is one of the most commonly diagnosed neuropsychiatric
      diseases, but the underlying mechanism and medicine are not well-known. Although
      Panax ginseng has been reported to exert protective effects in various
      neurological studies, little information is available regarding its
      antidepressant effects. Methods: Here, we examined the antidepressant effect and
      underlying mechanism of P. ginseng extract (PGE) in a chronic restraint stress
      (CRS)-induced depression model in mice. Results: Oral administration of PGE for
      14 d decreased immobility (depression-like behaviors) time in forced swim and
      tail suspended tests after CRS induction, which corresponded with attenuation of
      the levels of serum adrenocorticotropic hormone and corticosterone, as well as
      attenuated c-Fos expression in the amygdala. PGE enhanced messenger RNA
      expression level of brain-derived neurotrophic factor but ameliorated microglial
      activation and neuroinflammation (the level of messenger RNA and protein
      expression of cyclooxygenase-2 and inducible nitric oxide synthase) in the
      amygdala of mice after CRS induction. Interestingly, 14-d treatment with
      celecoxib, a selective cyclooxygenase-2 inhibitor, and Nomega-nitro-L-arginine
      methyl ester hydrochloride, a selective inducible nitric oxide synthase
      inhibitor, attenuated depression-like behaviors after CRS induction.
      Additionally, PGE inhibited the upregulation of the nuclear factor erythroid 2
      related factor 2 and heme oxygenase-1 pathways. Conclusion: Taken together, our
      findings suggest that PGE exerts antidepressant-like effect of CRS-induced
      depression by antineuroinflammatory and antioxidant (nuclear factor erythroid 2
      related factor 2/heme oxygenase-1 activation) activities by inhibiting the
      hypothalamo-pituitary-adrenal axis mechanism. Further studies are needed to
      evaluate the potential of components of P. ginseng as an alternative treatment of
      depression, including clinical trial evaluation.

PMID- 29348730
TI  - Black ginseng activates Akt signaling, thereby enhancing myoblast differentiation
      and myotube growth.
AB  - Background: Black ginseng (BG) has greatly enhanced pharmacological activities
      relative to white or red ginseng. However, the effect and molecular mechanism of
      BG on muscle growth has not yet been examined. In this study, we investigated
      whether BG could regulate myoblast differentiation and myotube hypertrophy.
      Methods: BG-treated C2C12 myoblasts were differentiated, followed by
      immunoblotting for myogenic regulators, immunostaining for a muscle marker,
      myosin heavy chain or immunoprecipitation analysis for myogenic transcription
      factors. Results: BG treatment of C2C12 cells resulted in the activation of Akt,
      thereby enhancing heterodimerization of MyoD and E proteins, which in turn
      promoted muscle-specific gene expression and myoblast differentiation. BG-treated
      myoblasts formed larger multinucleated myotubes with increased diameter and
      thickness, accompanied by enhanced Akt/mTOR/p70S6K activation. Furthermore, the
      BG treatment of human rhabdomyosarcoma cells restored myogenic differentiation.
      Conclusion: BG enhances myoblast differentiation and myotube hypertrophy by
      activating Akt/mTOR/p70S6k axis. Thus, our study demonstrates that BG has
      promising potential to treat or prevent muscle loss related to aging or other
      pathological conditions, such as diabetes.

PMID- 29348731
TI  - Problems with precaution: the transfusion medicine experience.
AB  - The precautionary principle is a dominant paradigm governing risk-based decision
      making. Today, there are increasing pressures to re-examine aggressive
      precautionary approaches, and to assess how the principle should be applied in
      the modern system. In this paper, we examined three key applications of
      precautionary approaches in the field of transfusion medicine to provide insight
      into the risks and benefits of these approaches. The three case studies examined
      were the donor deferral policies to safeguard against transfusion transmission of
      human immunodeficiency virus, variant Creutzfeldt-Jacob disease, and, lastly,
      xenotropic murine leukemia virus-related virus. Characterization of precautionary
      applications was conducted using an embedded case study design. Our findings
      indicate that transfusion transmission mitigation strategies have become
      increasingly aggressive in the face of theoretical risks. In contrast, the review
      processes for implementation and reversal of precautionary policies have been
      slow, and historical donor deferral policies are still in place today.
      Application of precautionary approaches has proved challenging with both benefits
      and pitfalls. In light of emerging threats to the blood system, policy-makers
      should consider the implementation of frameworks to guide the appropriate
      application of precaution in transfusion medicine in the future.

PMID- 29348732
TI  - A Flexible System for Cultivation of Methanococcus and Other Formate-Utilizing
      Methanogens.
AB  - Many hydrogenotrophic methanogens use either H2 or formate as the major electron
      donor to reduce CO2 for methane production. The conventional cultivation of these
      organisms uses H2 and CO2 as the substrate with frequent replenishment of gas
      during growth. H2 is explosive and requires an expensive gassing system to handle
      safely. Formate is as an ideal alternative substrate from the standpoints of both
      economy and safety but leads to large changes in the culture pH during growth.
      Here, we report that glycylglycine is an inexpensive and nontoxic buffer suitable
      for growth of Methanococcus maripaludis and Methanothermococcus okinawensis. This
      cultivation system is suitable for growth on liquid as well as solid medium in
      serum bottles. Moreover, it allows cultivation of liter scale cultures without
      expensive fermentation equipment. This formate cultivation system provides an
      inexpensive and flexible alternative for the growth of formate-utilizing,
      hydrogenotrophic methanogens.

PMID- 29348733
TI  - Monte Carlo calculation of photo-neutron dose produced by circular cones at 18 MV
      photon beams.
AB  - Aim: The aim of this study is to calculate neutron contamination at the presence
      of circular cones irradiating by 18 MV photons using Monte Carlo code.
      Background: Small photon fields are one of the most useful methods in
      radiotherapy. One of the techniques for shaping small photon beams is applying
      circular cones made of lead. Using this method in high energy photon due to
      neutron contamination is a crucial issue. Materials and methods: Initially,
      Varian linac producing 18 MV photons was simulated and after validating the code,
      various circular cones were also simulated. Then, the number of neutrons, neutron
      equivalent dose and absorbed dose per Gy of photon dose were calculated along the
      central axis. Results: Number of neutrons per Gy of photon dose had their maximum
      value at depth of 2 cm and these values for 5, 10, 15, 20 and 30 mm circular
      cones were 9.02, 7.76, 7.61, 6.02 and 5.08 (n cm-2 Gy-1), respectively. Neutron
      equivalent doses per Gy of photon dose had their maximum at the surface of the
      phantom and these values for mentioned collimators were 1.48, 1.33, 1.31, 1.12
      and 1.08 (mSv Gy-1), respectively. Neutron absorbed doses had their maximum at
      the surface of the phantom and these values for mentioned collimators sizes were
      103.74, 99.71, 95.77, 81.46 and 78.20 (MUGy/Gy), respectively. Conclusions: As
      the field size gets smaller, number of neutrons, equivalent and absorbed dose per
      Gy of photon increase. Also, neutron equivalent dose and absorbed dose are
      maximum at the surface of phantom and then these values will be decreased.

PMID- 29348735
TI  - Dosimetric evaluation of image based brachytherapy using tandem ovoid and tandem
      ring applicators.
AB  - Aim: The aim of the study is to evaluate the differences in dosimetry between
      tandem-ovoid and tandem-ring gynaecologic brachytherapy applicators in image
      based brachytherapy. Background: Traditionally, tandem ovoid applicators were
      used to deliver dose to tumor in intracavitary brachytherapy. Tandem-ring, tandem
      cylinder and hybrid intracavitary, interstitial applicators are also used
      nowadays in cervical cancer brachytherapy. Methods and materials: 100 CT datasets
      of cervical cancer patients (stage IB2 - IIIB) receiving HDR application (50
      tandem-ovoid and 50 tandem-ring) were studied. Brachytherapy was delivered using
      a CT-MRI compatible tandem-ovoid (50 patients) and a tandem-ring applicator (50
      patients). DVHs were calculated and D2cc was recorded for the bladder and rectum
      and compared with the corresponding ICRU point doses. The point B dose, the
      treated volume, high dose volume and the treatment time were recorded and
      compared for the two applicators. Results: The mean D2cc of the bladder with TR
      applicator was 6.746 Gy. TO applicator delivered a mean D2cc of 7.160 Gy to the
      bladder. The mean ICRU bladder points were 5.60 and 5.63 Gy for TR and TO
      applicator, respectively. The mean D2cc of the rectum was 4.04 Gy and 4.79 Gy for
      TR and TO applicators, respectively. The corresponding ICRU point doses were 5.10
      Gy and 5.66 Gy, respectively. Conclusions: The results indicate that the OAR
      doses assessed by DVH criteria were higher than ICRU point doses for the bladder
      with both tandem-ovoid and tandem-ring applicators whereas DVH based dose was
      lower than ICRU dose for the rectum. The point B dose, the treated volume and
      high dose volume was found to be slightly higher with the tandem-ovoid
      applicator. The mean D2cc dose for the bladder and rectum was lower with tandem
      ring applicators. The clinical implication of the above dosimetric differences
      needs to be evaluated further.

PMID- 29348734
TI  - Energy spectrum and dose enhancement due to the depth of the Lipiodol position
      using flattened and unflattened beams.
AB  - Aim: Lipiodol was used for stereotactic body radiotherapy combining trans
      arterial chemoembolization. Lipiodol used for tumour seeking in trans arterial
      chemoembolization remains in stereotactic body radiation therapy. In our previous
      study, we reported the dose enhancement effect in Lipiodol with 10* flattening
      filter-free (FFF). The objective of our study was to evaluate the dose
      enhancement and energy spectrum of photons and electrons due to the Lipiodol
      depth with flattened (FF) and FFF beams. Methods: FF and FFF for 6 MV beams from
      TrueBeam were used in this study. The Lipiodol (3 * 3 * 3 cm3) was located at
      depths of 1, 3, 5, 10, 20, and 30 cm in water. The dose enhancement factor (DEF)
      and the energy fluence were obtained by Monte Carlo calculations of the particle
      and heavy ion transport code system (PHITS). Results: The DEFs at the centre of
      Lipiodol with the FF beam were 6.8, 7.3, 7.6, 7.2, 6.1, and 5.7% and those with
      the FFF beam were 20.6, 22.0, 21.9, 20.0, 12.3, and 12.1% at depths of 1, 3, 5,
      10, 20, and 30 cm, respectively, where Lipiodol was located in water. Moreover,
      spectrum results showed that more low-energy photons and electrons were present
      at shallow depth where Lipiodol was located in water. The variation in the low
      energy spectrum due to the depth of the Lipiodol position was more explicit with
      the FFF beam than that with the FF beam. Conclusions: The current study revealed
      variations in the DEF and energy spectrum due to the depth of the Lipiodol
      position with the FF and FFF beams. Although the FF beam could reduce the effect
      of energy dependence due to the depth of the Lipiodol position, the dose
      enhancement was overall small. To cause a large dose enhancement, the FFF beam
      with the distance of the patient surface to Lipiodol within 10 cm should be used.

PMID- 29348736
TI  - Reducing Public Health Risk During Disasters: Identifying Social Vulnerabilities.
AB  - All regions of the US experience disasters which result in a number of negative
      public health consequences. Some populations have higher levels of social
      vulnerability and, thus, are more likely to experience negative impacts of
      disasters including emotional distress, loss of property, illness, and death. To
      mitigate the impact of disasters on at-risk populations, emergency managers must
      be aware of the social vulnerabilities within their community. This paper
      describes a qualitative study which aimed to understand how emergency managers
      identify social vulnerabilities, also referred to as at-risk populations, in
      their populations and barriers and facilitators to current approaches. Findings
      suggest that although public health tools have been developed to aid emergency
      managers in identifying at-risk populations, they are not being used
      consistently. Emergency managers requested more information on the availability
      of tools as well as guidance on how to increase ability to identify at-risk
      populations.

PMID- 29348738
TI  - Key Parameters on the Microwave Assisted Synthesis of Magnetic Nanoparticles for
      MRI Contrast Agents.
AB  - Uniform iron oxide magnetic nanoparticles have been synthesized using a microwave
      assisted synthesis method in organic media and their colloidal, magnetic, and
      relaxometric properties have been analyzed after its transference to water and
      compared with those nanoparticles prepared by thermal decomposition in organic
      media. The novelty of this synthesis relies on the use of a solid iron oleate as
      precursor, which assures the reproducibility and scalability of the synthesis,
      and the microwave heating that resulted in being faster and more efficient than
      traditional heating methods, and therefore it has a great potential for
      nanoparticle industrial production. The effect of different experimental
      conditions such as the solvent, precursor, and surfactant concentration and
      reaction time as well as the transference to water is analyzed and optimized to
      obtain magnetic iron oxide nanoparticles with sizes between 8 and 15 nm and
      finally colloids suitable for their use as contrast agents on Magnetic Resonance
      Imaging (MRI). The r2 relaxivity values normalized to the square of the
      saturation magnetization were shown to be constant and independent of the
      particle size, which means that the saturation magnetization is the main
      parameter controlling the efficiency of these magnetic nanoparticles as MRI T2
      contrast agents.

PMID- 29348739
TI  - Identification of Sensory Processing and Integration Symptom Clusters: A
      Preliminary Study.
AB  - Rationale: This study explored subtypes of sensory processing disorder (SPD) by
      examining the clinical presentations of cluster groups that emerged from scores
      of children with SPD on the Sensory Processing 3-Dimension (SP-3D) Inventory.
      Method: A nonexperimental design was used involving data extraction from the
      records of 252 children with SPD. Exploratory cluster analyses were conducted
      with scores from the SP-3D Inventory which measures sensory overresponsivity
      (SOR), sensory underresponsivity (SUR), sensory craving (SC), postural disorder,
      dyspraxia, and sensory discrimination. Scores related to adaptive behavior,
      social-emotional functioning, and attention among children with different sensory
      modulation patterns were then examined and compared. Results: Three distinct
      cluster groups emerged from the data: High SOR only, High SUR with SOR, and High
      SC with SOR. All groups showed low performance within multiple domains of
      adaptive behavior. Atypical behaviors associated with social-emotional
      functioning and attention varied among the groups. Implications: The SP-3D
      Inventory shows promise as a tool for assisting in identifying patterns of
      sensory dysfunction and for guiding intervention. Better characterization can
      guide intervention precision and facilitate homogenous samples for research.

PMID- 29348740
TI  - GA-Based Membrane Evolutionary Algorithm for Ensemble Clustering.
AB  - Ensemble clustering can improve the generalization ability of a single clustering
      algorithm and generate a more robust clustering result by integrating multiple
      base clusterings, so it becomes the focus of current clustering research.
      Ensemble clustering aims at finding a consensus partition which agrees as much as
      possible with base clusterings. Genetic algorithm is a highly parallel,
      stochastic, and adaptive search algorithm developed from the natural selection
      and evolutionary mechanism of biology. In this paper, an improved genetic
      algorithm is designed by improving the coding of chromosome. A new membrane
      evolutionary algorithm is constructed by using genetic mechanisms as evolution
      rules and combines with the communication mechanism of cell-like P system. The
      proposed algorithm is used to optimize the base clusterings and find the optimal
      chromosome as the final ensemble clustering result. The global optimization
      ability of the genetic algorithm and the rapid convergence of the membrane system
      make membrane evolutionary algorithm perform better than several state-of-the-art
      techniques on six real-world UCI data sets.

PMID- 29348737
TI  - In Vivo PET Imaging of Adenosine 2A Receptors in Neuroinflammatory and
      Neurodegenerative Disease.
AB  - Adenosine receptors are G-protein coupled P1 purinergic receptors that are
      broadly expressed in the peripheral immune system, vasculature, and the central
      nervous system (CNS). Within the immune system, adenosine 2A (A2A) receptor
      mediated signaling exerts a suppressive effect on ongoing inflammation. In
      healthy CNS, A2A receptors are expressed mainly within the neurons of the basal
      ganglia. Alterations in A2A receptor function and expression have been noted in
      movement disorders, and in Parkinson's disease pharmacological A2A receptor
      antagonism leads to diminished motor symptoms. Although A2A receptors are
      expressed only at a low level in the healthy CNS outside striatum, pathological
      challenge or inflammation has been shown to lead to upregulation of A2A receptors
      in extrastriatal CNS tissue, and this has been successfully quantitated using in
      vivo positron emission tomography (PET) imaging and A2A receptor-binding
      radioligands. Several radioligands for PET imaging of A2A receptors have been
      developed in recent years, and A2A receptor-targeting PET imaging may thus
      provide a potential additional tool to evaluate various aspects of
      neuroinflammation in vivo. This review article provides a brief overview of A2A
      receptors in healthy brain and in a selection of most important neurological
      diseases and describes the recent advances in A2A receptor-targeting PET imaging
      studies.

PMID- 29348741
TI  - AMOBH: Adaptive Multiobjective Black Hole Algorithm.
AB  - This paper proposes a new multiobjective evolutionary algorithm based on the
      black hole algorithm with a new individual density assessment (cell density),
      called "adaptive multiobjective black hole algorithm" (AMOBH). Cell density has
      the characteristics of low computational complexity and maintains a good balance
      of convergence and diversity of the Pareto front. The framework of AMOBH can be
      divided into three steps. Firstly, the Pareto front is mapped to a new objective
      space called parallel cell coordinate system. Then, to adjust the evolutionary
      strategies adaptively, Shannon entropy is employed to estimate the evolution
      status. At last, the cell density is combined with a dominance strength
      assessment called cell dominance to evaluate the fitness of solutions. Compared
      with the state-of-the-art methods SPEA-II, PESA-II, NSGA-II, and MOEA/D,
      experimental results show that AMOBH has a good performance in terms of
      convergence rate, population diversity, population convergence, subpopulation
      obtention of different Pareto regions, and time complexity to the latter in most
      cases.

PMID- 29348742
TI  - Emerging Trends in Machine Learning for Signal Processing.

PMID- 29348743
TI  - Fusion Methods for Biosignal Analysis: Theory and Applications.

PMID- 29348744
TI  - Improving EEG-Based Motor Imagery Classification for Real-Time Applications Using
      the QSA Method.
AB  - We present an improvement to the quaternion-based signal analysis (QSA) technique
      to extract electroencephalography (EEG) signal features with a view to developing
      real-time applications, particularly in motor imagery (IM) cognitive processes.
      The proposed methodology (iQSA, improved QSA) extracts features such as the
      average, variance, homogeneity, and contrast of EEG signals related to motor
      imagery in a more efficient manner (i.e., by reducing the number of samples
      needed to classify the signal and improving the classification percentage)
      compared to the original QSA technique. Specifically, we can sample the signal in
      variable time periods (from 0.5 s to 3 s, in half-a-second intervals) to
      determine the relationship between the number of samples and their effectiveness
      in classifying signals. In addition, to strengthen the classification process a
      number of boosting-technique-based decision trees were implemented. The results
      show an 82.30% accuracy rate for 0.5 s samples and 73.16% for 3 s samples. This
      is a significant improvement compared to the original QSA technique that offered
      results from 33.31% to 40.82% without sampling window and from 33.44% to 41.07%
      with sampling window, respectively. We can thus conclude that iQSA is better
      suited to develop real-time applications.

PMID- 29348745
TI  - Onychomycosis Caused by Fusarium spp. in Dakar, Senegal: Epidemiological,
      Clinical, and Mycological Study.
AB  - Fusarium spp. represent 9 to 44% of onychomycoses caused by fungi other than
      dermatophytes. This retrospective study describes 17 cases of Fusarium
      onychomycosis diagnosed at the Laboratory of Parasitology and Mycology of Le
      Dantec University Hospital in Dakar, Senegal, from 2014 to 2016. It included all
      patients received in the laboratory for suspicion of onychomycosis between
      January 1, 2014, and December 31, 2016. Diagnosis was based on mycological
      examination including direct examination and culture. Mycological analysis was
      considered positive when direct examination and culture were positive after at
      least one repeat. Seventeen Fusarium onychomycosis cases representing 12.9% of
      all onychomycoses reported were diagnosed. There were 5 cases on the fingernails
      and 12 on the toenails in 6 males and 11 females, and the mean age was 44 years
      (range: 26-64). Onychomycoses were diagnosed in immunocompetent patients except
      in a diabetic patient. The mean duration of lesions was 4.9 years (range: 1-15),
      and distal subungual onychomycosis was predominant. Almost all patients were from
      suburban areas of Dakar region. The most frequent species isolated belong to
      Fusarium solani complex. Because of the risk of disseminated infection in
      immunocompromised patients, realization of susceptibility tests is necessary to
      ensure better therapeutic management.

PMID- 29348747
TI  - Vitamin D Deficiency Is Associated with Endoscopic Severity in Patients with
      Crohn's Disease.
AB  - Background and Aims: Vitamin D deficiency is common in patients with Crohn's
      disease and is associated with disease activity. Relationship between vitamin D
      and endoscopic disease activity is unknown. The aim of the study is to determine
      the association between vitamin D status and endoscopic disease activity in CD
      patients. Methods: Consecutive hospitalized CD patients from 2014 to 2016 who
      received vitamin D assessment and colonoscopy were retrospectively evaluated.
      Clinical disease activity was assessed by Crohn's disease activity index and C
      reactive protein. Endoscopic activity was calculated using simple endoscopic
      score for Crohn's disease. Results: Median serum 25OHD level of 131 patients was
      lower than healthy controls [21.1 nmol/L (11.8-32.3) versus 49.9 nmol/L (44.9
      57.4), P = 0.007]. 125 (95%) patients had vitamin D deficiency and the rest (5%)
      had vitamin D insufficiency. Serum 25OHD was inversely correlated with CRP (r = 
      0.308, P < 0.001), CDAI (r = -0.582, P < 0.001), SES-CD (r = -0.294, P = 0.001),
      and endoscopic severity stratified by SES-CD (P = 0.001). Conclusion: Vitamin D
      deficiency was prevalent among hospitalized CD patients. Vitamin D levels were
      inversely correlated with endoscopic disease activity. Vitamin D status could be
      a biomarker in assessing disease activity among hospitalized CD patients in
      addition to CDAI and CRP.

PMID- 29348746
TI  - Impact of Time-Restricted Feeding and Dawn-to-Sunset Fasting on Circadian Rhythm,
      Obesity, Metabolic Syndrome, and Nonalcoholic Fatty Liver Disease.
AB  - Obesity now affects millions of people and places them at risk of developing
      metabolic syndrome, nonalcoholic fatty liver disease (NAFLD), and even
      hepatocellular carcinoma. This rapidly emerging epidemic has led to a search for
      cost-effective methods to prevent the metabolic syndrome and NAFLD as well as the
      progression of NAFLD to cirrhosis and hepatocellular carcinoma. In murine models,
      time-restricted feeding resets the hepatic circadian clock and enhances
      transcription of key metabolic regulators of glucose and lipid homeostasis.
      Studies of the effect of dawn-to-sunset Ramadan fasting, which is akin to time
      restricted feeding model, have also identified significant improvement in body
      mass index, serum lipid profiles, and oxidative stress parameters. Based on the
      findings of studies conducted on human subjects, dawn-to-sunset fasting has the
      potential to be a cost-effective intervention for obesity, metabolic syndrome,
      and NAFLD.

PMID- 29348748
TI  - Comment on "Differences in Ventilatory Threshold for Exercise Prescription in
      Outpatient Diabetic and Sarcopenic Obese Subjects".

PMID- 29348749
TI  - The Effect of Number of Teeth and Chewing Ability on Cognitive Function of
      Elderly in UAE: A Pilot Study.
AB  - Cognitive decline is one of the major causes of disability among the aging
      population. The aim of this study was to explore the relationship between oral
      health parameters (number of teeth, chewing ability, and presence of a denture)
      and cognitive function in the elderly across the UAE. Fifty persons (age >= 60;
      71.26 +/- 10.23) were enrolled in the study. Cognitive status was assessed using
      the standardized mini-mental state examination (SMMSE) and accordingly,
      cognitively normal subjects scoring >=24 were considered as the control group and
      cognitively impaired individuals scoring <=23 were considered as the low scoring
      group. Chewing ability was examined, number of teeth was noted, and demographical
      data was collected. The results of this pilot study showed that individuals with
      low SMMSE scores were significantly less educated (P < 0.01) and had fewer number
      of remaining teeth (P < 0.05) and impaired chewing ability (P < 0.05). These
      results demonstrate a significant link between the number of teeth, chewing
      ability, and cognitive function. However, this pilot study had its limitations
      and was the first of its kind in the UAE and Gulf region; therefore, future
      research addressing the limitations is needed to further explore this
      association.

PMID- 29348750
TI  - Recent Studies on the Speciation and Determination of Mercury in Different
      Environmental Matrices Using Various Analytical Techniques.
AB  - This paper reviews the current research on the speciation and determination of
      mercury by various analytical techniques, including the atomic absorption
      spectrometry (AAS), voltammetry, inductively coupled plasma optical emission
      spectrometry (ICP-OES), ICP-mass spectrometry (MS), atomic fluorescence
      spectrometry (AFS), spectrophotometry, spectrofluorometry, and high performance
      liquid chromatography (HPLC). Approximately 96 research papers on the speciation
      and determination of mercury by various analytical instruments published in
      international journals since 2015 were reviewed. All analytical parameters,
      including the limits of detection, linearity range, quality assurance and
      control, applicability, and interfering ions, evaluated in the reviewed articles
      were tabulated. In this review, we found a lack of information in speciation
      studies of mercury in recent years. Another important conclusion from this review
      was that there were few studies regarding the concentration of mercury in the
      atmosphere.

PMID- 29348751
TI  - Alkaloids Profiling of Fumaria capreolata by Analytical Platforms Based on the
      Hyphenation of Gas Chromatography and Liquid Chromatography with Quadrupole-Time
      of-Flight Mass Spectrometry.
AB  - Two analytical platforms, gas chromatography (GC) coupled to quadrupole-time-of
      flight (QTOF) mass spectrometry (MS) and reversed-phase ultrahigh performance
      liquid chromatography (UHPLC) coupled to diode array (DAD) and QTOF detection,
      were applied in order to study the alkaloid profile of Fumaria capreolata. The
      use of these mass analyzers enabled tentatively identifying the alkaloids by
      matching their accurate mass signals and suggested molecular formulae with those
      previously reported in libraries and databases. Moreover, the proposed structures
      were corroborated by studying their fragmentation pattern obtained by both
      platforms. In this way, 8 and 26 isoquinoline alkaloids were characterized using
      GC-QTOF-MS and RP-UHPLC-DAD-QTOF-MS, respectively, and they belonged to the
      following subclasses: protoberberine, protopine, aporphine, benzophenanthridine,
      spirobenzylisoquinoline, morphinandienone, and benzylisoquinoline. Moreover, the
      latter analytical method was selected to determine at 280 nm the concentration of
      protopine (9.6 +/- 0.7 mg/g), a potential active compound of the extract. In
      conclusion, although GC-MS has been commonly used for the analysis of this type
      of phytochemicals, RP-UHPLC-DAD-QTOF-MS provided essential complementary
      information. This analytical method can be applied for the quality control of
      phytopharmaceuticals containing Fumaria extracts currently found in the market.

PMID- 29348752
TI  - Infrared Drying as a Quick Preparation Method for Dried Tangerine Peel.
AB  - To establish the most convenient and effective method to dry tangerine peels,
      different methods (sun drying, hot-air drying, freeze drying, vacuum drying, and
      medium- and short-wave infrared drying) were exploited. Our results indicated
      that medium- and short-wave infrared drying was the best method to preserve
      nutraceutical components; for example, vitamin C was raised to 6.77 mg/g (D.W.)
      from 3.39 mg/g (sun drying). Moreover, the drying time can be shortened above 96%
      compared with sun drying. Importantly, the efficiency of DPPH radical scavenging
      was enhanced from 26.66% to 55.92%. These findings would provide a reliable and
      time-saving methodology to produce high-quality dried tangerine peels.

PMID- 29348753
TI  - Potential Effect of Leukocyte-Platelet-Rich Fibrin in Bone Healing of Skull Base:
      A Pilot Study.
AB  - Background: Reconstruction of surgical defects following cranial base surgery is
      challenging. Others have demonstrated that leukocyte-platelet-rich fibrin (L-PRF)
      stimulates tissue healing and bone regeneration. However, these studies have
      addressed mostly maxillofacial surgical wounds. Objective: The objective of this
      study was to assess the possible adjuvant role of L-PRF in inducing
      neoossification of the surgical bone defect in anterior skull base surgery.
      Methods: We identified patients who had undergone an endoscopic endonasal surgery
      of the anterior skull base in which L-PRF membranes were used for the
      reconstruction of the bone defect and who were followed up with postoperative CT
      scans. CT findings were then correlated with baseline scans and with the CT scans
      of a patient who had undergone imaging and histologic analysis after
      maxillofacial surgery in which L-PRF was used and in which we demonstrated bone
      formation. Results: Five patients fulfilled the inclusion criteria. In four
      patients, the CT scan demonstrated closure of the bony defect by neoosteogenesis;
      however, the bone appeared less dense than the surrounding normal bone. A
      comparison with the control patient yielded similar radiological features.
      Conclusion: This case series suggests that L-PRF may induce bone healing and
      regeneration at the surgical site defect. Multi-institutional studies with a
      larger series of patients are required to confirm this possibility.

PMID- 29348754
TI  - The Impact of Different Classification Criteria Sets on the Estimated Prevalence
      and Associated Risk Factors of Diastolic Dysfunction in Rheumatoid Arthritis.
AB  - This study compared the estimated prevalence and potential determinants of left
      ventricular (LV) diastolic dysfunction upon applying different classification
      criteria in rheumatoid arthritis (RA). LV diastolic function was assessed
      echocardiographically by pulsed Doppler (E/A), tissue Doppler (E/e', lateral and
      septal e'), and left atrial volume index in 176 RA patients. Relationships of
      traditional cardiovascular risk factors and RA characteristics with LV diastolic
      function and dysfunction according to previous and current criteria were
      determined in multivariate regression models. Waist-hip ratio was associated with
      E/A (standardised beta (SE) = -0.28 +/- 0.09, p = 0.0002) and lateral e'
      (standardised beta (SE) = 0.26 +/- 0.09, p = 0.01); low diastolic blood pressure
      was related to E/e' (standardised beta (SE) = -0.16 +/- 0.08, p = 0.04).
      Diastolic dysfunction prevalence differed upon applying previous (59%) compared
      to current (22%) criteria (p < 0.0001). One SD increase in waist-hip ratio was
      associated with diastolic dysfunction when applying current criteria (OR = 2.61
      (95% CI = 1.51-4.52), p = 0.0006), whereas one SD increase in diastolic blood
      pressure was inversely related to diastolic dysfunction upon using previous
      criteria (OR = 0.57 (95% CI = 0.40-0.81), p = 0.002). In conclusion, application
      of current and previous diastolic dysfunction criteria markedly alters the
      prevalence and risk factors associated with diastolic dysfunction in RA.

PMID- 29348755
TI  - Incidentally Discovered Extranodal Marginal Zone B-Cell Lymphoma of Mucosa
      Associated Lymphoid Tissue in the Colon.
AB  - We present a case of colonic mucosa-associated lymphoid tissue (MALT) lymphoma in
      a 62-year-old woman diagnosed after a positive test for fecal occult blood.

PMID- 29348756
TI  - Neurolysis for Treatment of Infraorbital Neuropathy.
AB  - Two patients, a woman aged 34 and a man aged 56, were included in the study. They
      reported the existence of pain in the areas of the infraorbital nerve, which,
      over the last four to five years, aggravated by the stimuli of eating, laughing,
      and being touched. 2 ml of 0.5% lidocaine was administered to these patients six
      times percutaneously. It was observed that the ease of pain lasted until the
      local anesthesia lost its effect, and the pain resumed its original intensity.
      Neurolysis with 0.5 ml of 50% ethanol was applied to the infraorbital nerve. This
      procedure was applied to the first patient twice and three times to the second.
      Thereafter, the patients were cured completely. For the treatment of idiopathic
      chronic infraorbital neuropathy, the neurolysis of the infraorbital nerve using
      50% ethanol could be considered as an effective treatment alternative.

PMID- 29348757
TI  - Corrigendum to "Subdural Empyema Complicating Bacterial Meningitis: A Challenging
      Diagnosis in a Patient with Polysubstance Abuse".
AB  - [This corrects the article DOI: 10.1155/2015/931819.].

PMID- 29348759
TI  - The Flavonoid Glabridin Induces OCT4 to Enhance Osteogenetic Potential in
      Mesenchymal Stem Cells.
AB  - Mesenchymal stem cells (MSCs) are a promising tool for studying intractable
      diseases. Unfortunately, MSCs can easily undergo cellular senescence during in
      vitro expansion by losing stemness. The aim of this study was to improve the
      stemness and differentiation of MSCs by using glabridin, a natural flavonoid.
      Assessments of cell viability, cell proliferation, beta-galactosidase activity,
      differentiation, and gene expression by reverse transcription PCR were
      subsequently performed in the absence or presence of glabridin. Glabridin
      enhanced the self-renewal capacity of MSCs, as indicated by the upregulation of
      the OCT4 gene. In addition, it resulted in an increase in the osteogenic
      differentiation potential by inducing the expression of osteogenesis-related
      genes such as DLX5 and RUNX2. We confirmed that glabridin improved the
      osteogenesis of MSCs with a significant elevation in the expression of
      OSTEOCALCIN and OSTEOPONTIN genes. Taken together, these results suggest that
      glabridin enhances osteogenic differentiation of MSCs with induction of the OCT4
      gene; thus, glabridin could be useful for stem cell-based therapies.

PMID- 29348760
TI  - The Effects of BMP-2, miR-31, miR-106a, and miR-148a on Osteogenic
      Differentiation of MSCs Derived from Amnion in Comparison with MSCs Derived from
      the Bone Marrow.
AB  - Mesenchymal stromal cells (MSCs) offering valuable anticipations for the
      treatment of degenerative diseases. They can be found in many tissues including
      amnion. MSCs from amnion (AM-MSCs) can differentiate into osteoblast similar to
      that of bone marrow-derived MSCs (BM-MSCs). However, the ability is not much
      efficient compared to BM-MSCs. This study aimed to examine the effects of BMP-2
      and miRNAs on osteogenic differentiation of AM-MSCs compared to those of BM-MSCs.
      The osteogenic differentiation capacity after miRNA treatment was assessed by ALP
      expression, ALP activity, and osteogenic marker gene expression. The results
      showed that the osteogenic differentiation capacity increased after BMP-2
      treatment both in AM-MSCs and BM-MSCs. MiR-31, miR-106a, and miR-148a were
      downregulated during the osteogenic differentiation. After transfection with anti
      miRNAs, ALP activity and osteogenic genes were increased over the time of
      differentiation. The data lead to the potential for using AM-MSCs as an
      alternative source for bone regeneration. Moreover, the information of miRNA
      expression and function during osteogenic differentiation may be useful for the
      development of new therapeutics or enhanced an in vitro culture technique
      required for stem cell-based therapies in the bone regeneration.

PMID- 29348761
TI  - Prevalence of Middle Ear Infections and Associated Risk Factors in Children under
      5 Years in Gasabo District of Kigali City, Rwanda.
AB  - Middle ear infections are common in children, and delay in diagnosis and
      treatment may result in complications such as delays in speech and language
      development and deafness. The aim of this study was to determine the prevalence
      and care seeking behaviour for middle ear infections in children under five years
      in Kigali city. We conducted a cross-sectional study among 810 children aged 6-59
      months in Gasabo district of Kigali city, Rwanda. The prevalence of middle ear
      infections was 5.8%, of whom 4% had chronic suppurative otitis media. A child was
      less likely to develop middle ear infections if they lived in an urban setting
      (OR = 0.52, 95% CI: 0.285-0.958) but more likely to develop middle ear infections
      if exposed to household smoke (OR = 2.54, 95% CI: 1.18-5.46). Parents were
      unlikely to know that their child had an ear infection (OR: 0.15, 95% CI: 0.06
      0.34). Middle ear infection remains a public health problem in Rwanda but many
      parents were not aware of its presence in the affected children. There is a need
      to raise awareness of parents about ear infection and to promote early care
      seeking from qualified health workers.

PMID- 29348758
TI  - Lymphocytes in Placental Tissues: Immune Regulation and Translational
      Possibilities for Immunotherapy.
AB  - Immune modulation at the fetomaternal interface is crucial to ensure that the
      fetal allograft is not rejected. In the present review, the focus is to describe
      basic functions of lymphocyte populations and how they may contribute to
      fetomaternal immune regulation, as well as determining what proportions and
      effector functions of these cells are reported to be present in placental tissues
      in humans. Also explored is the possibility that unique cell populations at the
      fetomaternal interface may be targets for adoptive cell therapy. Increasing the
      understanding of immune modulation during pregnancy can give valuable insight
      into other established fields such as allogeneic hematopoietic stem cell
      transplantation and solid organ transplantation. In these settings, lymphocytes
      are key components that contribute to inflammation and rejection of either
      patient or donor tissues following transplantation. In contrast, an allogeneic
      fetus eludes rejection by the maternal immune system.

PMID- 29348762
TI  - Kerosene Oil Poisoning among Children in Rural Sri Lanka.
AB  - Introduction: Kerosene oil poisoning is one of common presentations to emergency
      departments among children in rural territories of developing countries. This
      study aimed to describe clinical manifestations, reasons for delayed
      presentations, harmful first aid practices, complications, and risk factors
      related to kerosene oil poisoning among children in rural Sri Lanka. Methods:
      This multicenter study was conducted in North-Central province of Sri Lanka
      involving all in-patient children with acute kerosene oil poisoning. Data were
      collected over seven years from thirty-six hospitals in the province. Data
      collection was done by pretested, multistructured questionnaires and a
      qualitative study. Results: Male children accounted for 189 (60.4%) while 283
      (93%) children were below five years. The majority of parents belonged to farming
      community. Most children ingested kerosene oil in home kitchen. Mortality rate
      was 0.3%. Lack of transport facilities and financial resources were common
      reasons for delayed management. Hospital transfer rate was 65.5%. Thirty percent
      of caregivers practiced harmful first aid measures. Commonest complication was
      chemical pneumonitis. Strongest risk factors for kerosene oil poisoning were
      unsafe storage, inadequate supervision, and inadequate house space. Conclusions:
      Effect of safe storage and community education in reducing the burden of kerosene
      oil poisoning should be evaluated. Since many risk factors interact to bring
      about the event of poisoning in a child, holistic approaches to community
      education in rural settings are recommended.

PMID- 29348764
TI  - Study on the Clinical Safe and Effective Methods of Arsenic-Containing Compound
      Qinghuang Powder in the Treatment of Myelodysplastic Syndrome.
AB  - Objective: To establish the clinical safe and effective methods of arsenic
      containing compound-Qinghuang Powder (compound-QHP) in the treatment of
      myelodysplastic syndrome (MDS). Methods: 200 patients with MDS were treated with
      compound-QHP (daily dose of 0.1 g realgar). The blood arsenic concentrations
      (BACs) were detected by atomic fluorescence spectrophotometry (HF-AFS). After
      treatment for 1 month, the patients were randomly divided into group A and group
      B when the BACs were less than 20 MUg/L. Daily dose of realgar was maintained in
      group A and it was increased to that when the BACs were more than 20 MUg/L in
      group B. The BAC and clinical efficacy and safety in two groups were compared at
      the end of the treatment with compound-QHP. Results: The average BAC of group B
      was significantly higher than that of group A (P < 0.01). The rates of hematology
      improvement and reduced transfusion were significantly higher in group B than in
      group A (P < 0.05). The HGB, ANC, and PLT significantly increased in group B
      after treatment (P > 0.05). Conclusions: Monitoring the BAC and adjusting the
      daily dose of realgar to increase the effective BAC and then improving efficacy
      without increasing the clinical toxicity are the clinical safe and effective
      methods in the treatment of MDS.

PMID- 29348763
TI  - Inflammasomes in Mycobacterium tuberculosis-Driven Immunity.
AB  - The development of effective innate and subsequent adaptive host immune responses
      is highly dependent on the production of proinflammatory cytokines that increase
      the activity of immune cells. The key role in this process is played by
      inflammasomes, multimeric protein complexes serving as a platform for caspase-1,
      an enzyme responsible for proteolytic cleavage of IL-1beta and IL-18 precursors.
      Inflammasome activation, which triggers the multifaceted activity of these two
      proinflammatory cytokines, is a prerequisite for developing an efficient
      inflammatory response against pathogenic Mycobacterium tuberculosis (M.tb). This
      review focuses on the role of NLRP3 and AIM2 inflammasomes in M.tb-driven
      immunity.

PMID- 29348765
TI  - Preventive Effect and Safety of a Follicle Stimulating Hormone Inhibitory
      Formulation Containing a Mixture of Coicis Semen and Artemisia capillaris for
      Precocious Puberty: A Preliminary Experimental Study Using Female Rats.
AB  - Background: Precocious puberty is a common endocrine disease in children.
      Inappropriate activation of hypothalamic-pituitary-gonadal axis leads to the
      development of secondary sexual characteristics at an earlier age than normal
      children and causes short stature in adulthood. Objectives: The aim of this study
      is to evaluate the preventive effects of a herbal formulation containing a
      mixture of Coicis Semen and Artemisia capillaris (hEIF extract) on precocious
      puberty. Methods: The preventive effect of hEIF extract on precocious puberty in
      rats was evaluated by measuring blood component after 3 weeks of treatment via
      oral administration. Network pharmacological analyses were performed to predict
      the bioactive components of hEIF extract. Results: In vivo studies showed that
      hEIF extract significantly reduced follicle stimulating hormone (FSH) levels.
      After treatment with 200 mg/kg of hEIF extract, the FSH level was 5.33 +/- 1.10
      ng/mL, whereas the FSH level in the vehicle group was 46.73 +/- 0.80 ng/mL.
      Moreover, the use of hEIF extract did not stimulate body growth and bone
      accretion in rats. The network pharmacological analysis led to the identification
      of multiple targets of hEIF extract related to lipolysis and the female sex
      hormone-related pathways. Conclusion: hEIF extract can be used as an FSH
      inhibitor for the treatment of precocious puberty.

PMID- 29348766
TI  - Inhibition of Tumor Growth of Human Hepatocellular Carcinoma HepG2 Cells in a
      Nude Mouse Xenograft Model by the Total Flavonoids from Arachniodes exilis.
AB  - A tumor growth model of human hepatocellular carcinoma HepG2 cells in nude mice
      was employed to investigate the antitumor activity of the total flavonoids
      extracted from Arachniodes exilis (TFAE) in vivo. Several biochemical assays
      including hematoxylin-eosin (HE) staining, immunohistochemistry, and Western blot
      were performed to elucidate the mechanism of action of total flavonoids extracted
      from Arachniodes exilis (TFAE). The results showed that TFAE effectively
      inhibited the tumor growth of hepatocellular carcinoma in nude mice and had no
      significant effect on body weight, blood system, and functions of liver and
      kidney. Expression levels of proapoptotic proteins Bax and cleaved caspase-3
      remarkably increased while the expressions of Bcl-2, HIF-1alpha, and VEGF were
      suppressed by TFAE. These results suggested that the antitumor potential of TFEA
      was implied by the apoptosis of tumor cells and the inhibition of angiogenesis in
      tumor tissue.

PMID- 29348767
TI  - Dangguijihwang-tang and Dangguijakyak-san Prevent Menopausal Symptoms and
      Dangguijihwang-tang Prevents Articular Cartilage Deterioration in Ovariectomized
      Obese Rats with Monoiodoacetate-Induced Osteoarthritis.
AB  - We investigated whether dangguijakyak-san (DJY) and dangguijihwang-tang (DJH),
      oriental medicines traditionally used for inflammatory diseases, could prevent
      and/or delay the progression of postmenopausal symptoms and osteoarthritis in
      osteoarthritis-induced estrogen-deficient rats. Treated ovariectomized (OVX) rats
      consumed either 1% DJY or 1% DJH in the diets. Positive-control rats were given
      30 MUg/kg bw 17beta-estradiol and control rats were given 1% fat as were the
      normal-control rats. All rats received high-fat diets for 8 weeks. At the 9th
      week, OVX rats received articular injections of monoiodoacetate (MIA) or saline
      (normal control) into the right knee. At 3 weeks after MIA injection, DJY reduced
      visceral-fat mass and improved glucose metabolism by reducing insulin resistance,
      whereas DJH increased BMD and decreased insulin resistance. DJH improved weight
      distribution in the right knee and maximum running velocity on a treadmill at
      days 14 and 21 as much as those of the positive control. TNF-alpha, IL-1beta, and
      IL-6 levels in articular cartilage were much higher in the control than the
      positive control, whereas both DJY and DJH reduced the levels to those of the
      positive control. The histological analysis assessed articular cartilage damage
      near the tidemark and proteoglycan loss in the control versus the positive
      control; DJY and DJH prevented this damage and proteoglycan loss. In conclusion,
      DJY may provide an effective treatment for improving glucose tolerance, and DJH
      may be appropriate for preventing osteoarthritis.

PMID- 29348768
TI  - Investigating the Mechanisms of Action of Depside Salt from Salvia miltiorrhiza
      Using Bioinformatic Analysis.
AB  - Salvia miltiorrhiza is a traditional Chinese medicinal herb used for treating
      cardiovascular diseases. Depside salt from S. miltiorrhiza (DSSM) contains the
      following active components: magnesium lithospermate B, lithospermic acid, and
      rosmarinic acid. This study aimed to reveal the mechanisms of action of DSSM.
      After searching for DSSM-associated genes in GeneCards, Search Tool for
      Interacting Chemicals, SuperTarget, PubChem, and Comparative Toxicogenomics
      Database, they were subjected to enrichment analysis using Multifaceted Analysis
      Tool for Human Transcriptome. A protein-protein interaction (PPI) network was
      visualised; module analysis was conducted using the Cytoscape software. Finally,
      a transcriptional regulatory network was constructed using the TRRUST database
      and Cytoscape. Seventy-three DSSM-associated genes were identified. JUN, TNF,
      NFKB1, and FOS were hub nodes in the PPI network. Modules 1 and 2 were identified
      from the PPI network, with pathway enrichment analysis, showing that the presence
      of NFKB1 and BCL2 in module 1 was indicative of a particular association with the
      NF-kappaB signalling pathway. JUN, TNF, NFKB1, FOS, and BCL2 exhibited notable
      interactions among themselves in the PPI network. Several regulatory
      relationships (such as JUN -> TNF/FOS, FOS -> NFKB1 and NFKB1 -> BCL2/TNF) were
      also found in the regulatory network. Thus, DSSM exerts effects against
      cardiovascular diseases by targeting JUN, TNF, NFKB1, FOS, and BCL2.

PMID- 29348769
TI  - Research and Development of Atractylodes lancea (Thunb) DC. as a Promising
      Candidate for Cholangiocarcinoma Chemotherapeutics.
AB  - Treatment and control of cholangiocarcinoma (CCA): the bile duct cancer is
      limited by the lack of effective chemotherapeutic drugs and alternative drugs are
      needed, particularly those from natural sources. This article reviews steps of
      research and development of Atractylodes lancea (Thunb) DC. (AL) as potential
      candidate for CCA chemotherapy, with adoption of the reverse pharmacology
      approach. Major steps include (1) reviewing of existing information on its
      phytochemistry and pharmacological properties, (2) screening of its activities
      against CCA, (3) standardization of AL, (4) nonclinical studies to evaluate anti
      CCA activities, (5) phytochemistry and standardization of AL extract, (6)
      development of oral pharmaceutical formulation of standardized AL extract, and
      (7) toxicity testing of oral pharmaceutical formulation of standardized AL
      extract. Results from a series of our study confirm anti-CCA potential and safety
      profiles of both the crude extract and the finished product (oral pharmaceutical
      formulation of the standardized AL extract). Phases I and II clinical trials of
      the product to confirm tolerability and efficacy in healthy subjects and patients
      with advanced stage CCA will be carried out soon.

PMID- 29348770
TI  - Vitamin E-Mediated Modulation of Glutamate Receptor Expression in an Oxidative
      Stress Model of Neural Cells Derived from Embryonic Stem Cell Cultures.
AB  - Glutamate is the primary excitatory neurotransmitter in the central nervous
      system. Excessive concentrations of glutamate in the brain can be excitotoxic and
      cause oxidative stress, which is associated with Alzheimer's disease. In the
      present study, the effects of vitamin E in the form of tocotrienol-rich fraction
      (TRF) and alpha-tocopherol (alpha-TCP) in modulating the glutamate receptor and
      neuron injury markers in an in vitro model of oxidative stress in neural-derived
      embryonic stem (ES) cell cultures were elucidated. A transgenic mouse ES cell
      line (46C) was differentiated into a neural lineage in vitro via induction with
      retinoic acid. These cells were then subjected to oxidative stress with a
      significantly high concentration of glutamate. Measurement of reactive oxygen
      species (ROS) was performed after inducing glutamate excitotoxicity, and recovery
      from this toxicity in response to vitamin E was determined. The gene expression
      levels of glutamate receptors and neuron-specific enolase were elucidated using
      real-time PCR. The results reveal that neural cells derived from 46C cells and
      subjected to oxidative stress exhibit downregulation of NMDA, kainate receptor,
      and NSE after posttreatment with different concentrations of TRF and alpha-TCP, a
      sign of neurorecovery. Treatment of either TRF or alpha-TCP reduced the levels of
      ROS in neural cells subjected to glutamate-induced oxidative stress; these
      results indicated that vitamin E is a potent antioxidant.

PMID- 29348771
TI  - A Review on the Medicinal Plant Dalbergia odorifera Species: Phytochemistry and
      Biological Activity.
AB  - The crucial medicinal plant Dalbergia odorifera T. Chen species belongs to genus
      Dalbergia, with interesting secondary metabolites, consisting of main classes of
      flavonoid, phenol, and sesquiterpene derivatives, as well as several
      arylbenzofurans, quinones, and fatty acids. Biological studies were carried out
      on extracts, fractions, and compounds from this species involved in cytotoxic
      assays; antibacterial, antioxidative, anti-inflammatory, antithrombotic,
      antiplatelet, antiosteosarcoma, antiosteoporosis, antiangiogenesis, and
      prostaglandin biosynthetic enzyme inhibition activities; vasorelaxant activities;
      alpha-glucosidase inhibitory activities; and many other effects. In terms of the
      valuable resources for natural new drugs development, D. odorifera species are
      widely used as medicinal drugs in many countries for treatment of cardiovascular
      diseases, cancer, diabetes, blood disorders, ischemia, swelling, necrosis, or
      rheumatic pain. Although natural products from this plant have been increasingly
      playing an important role in drug discovery programs, there is no supportive
      evidence to provide a general insight into phytochemical studies on D. odorifera
      species and biological activities of extracts, fractions, and isolated compounds.
      To a certain extent, this review deals with an overview of almost naturally
      occurring compounds from this species, along with extensive coverage of their
      biological evaluations.

PMID- 29348772
TI  - Kyungheechunggan-Tang-01, a New Herbal Medication, Suppresses LPS-Induced
      Inflammatory Responses through JAK/STAT Signaling Pathway in RAW 264.7
      Macrophages.
AB  - Medicinal plants have been used as alternative therapeutic tools to alleviate
      inflammatory diseases. The objective of this study was to evaluate anti
      inflammatory properties of Kyungheechunggan-tang- (KCT-) 01, KCT-02, and
      Injinchunggan-tang (IJCGT) as newly developed decoctions containing 3-11 herbs in
      LPS-induced macrophages. KCT-01 showed the most potent inhibitory effects on LPS
      induced NO, PGE2, TNF-alpha, and IL-6 production among those three herbal
      formulas. In addition, KCT-01 significantly inhibited LPS-induced iNOS and COX-2
      at protein levels and expression of iNOS, COX-2, TNF-alpha, and IL-6 at mRNA
      levels. Molecular data revealed that KCT-01 attenuated the activation of JAK/STAT
      signaling cascade without affecting NF-kappaB or AP-1 activation. In ear
      inflammation induced by croton oil, KCT-01 significantly reduced edema, MPO
      activity, expression levels of iNOS and COX-2, and STAT3 phosphorylation in ear
      tissues. Taken together, our findings suggest that KCT-01 can downregulate the
      expression of proinflammatory genes by inhibiting JAK/STAT signaling pathway
      under inflammatory conditions. This study provides useful data for further
      exploration and application of KCT-01 as a potential anti-inflammatory medicine.

PMID- 29348773
TI  - Poly-epsilon-Caprolactone Microsphere Polymers Containing Usnic Acid: Acute
      Toxicity and Anti-Inflammatory Activity.
AB  - Usnic acid (UA) has been studied by its pharmacological properties; however, it
      presents moderate toxicity, low solubility, and absorption by biological
      membranes. The aim of this study was to develop poly-epsilon-caprolactone
      microsphere polymers containing UA (UA-micro) and evaluate their acute toxicity
      and anti-inflammatory activity. The microspheres were prepared by multiple
      emulsion technique (water/oil/water) and characterized by the encapsulation
      efficiency, particle size, polydispersity index, and zeta potential. The acute
      toxicity of UA and UA-micro (25-50 mg/kg; p.o.) was evaluated in mice. The anti
      inflammatory activity of UA and UA-micro was evaluated by subcutaneous air pouch
      and carrageenan-induced paw edema in rat, with measurement of inflammatory
      cytokines and MPO levels. The UA presented encapsulation efficiency of 97.72%,
      particle size of 13.54 micrometers, polydispersity index of 2.36, and zeta
      potential of 44.5 +/- 2.95 mV. The UA-micro presented lower acute toxicity (LD50
      value up to 2000 mg/kg; p.o.) when compared to UA. UA-micro and UA (25 mg/kg)
      significantly reduced paw volume and decreased MPO levels, whereas only UA-micro
      (50 mg/kg) reduced significantly IL-1beta, TNF-alpha, and NO levels in
      inflammatory exudate. These results suggest that controlled release systems, as
      microspheres, can be a promising alternative to reduce the toxicity of UA, making
      it a viable compound for inflammation therapy.

PMID- 29348774
TI  - Five Indigenous Plants of Pakistan with Antinociceptive, Anti-Inflammatory,
      Antidepressant, and Anticoagulant Properties in Sprague Dawley Rats.
AB  - Five medicinal plants of Pakistan were investigated for their antinociceptive,
      anti-inflammatory, antidepressant, and anticoagulant potential. Antinociceptive
      activity was estimated by hot plate and writhing assay. In hot plate assay,
      Quercus dilatata (52.2%) and Hedera nepalensis (59.1%) showed moderate while
      Withania coagulans (65.3%) displayed a significant reduction in pain. On the
      other hand, in writhing assay, Quercus dilatata (49.6%), Hedera nepalensis
      (52.7%), and Withania coagulans (62.0%) showed comparative less activity. In anti
      inflammatory assays crude extracts showed significant edema inhibition in a dose
      dependent manner. In carrageenan assay, the highest activity was observed for
      Withania coagulans (70.0%) followed by Quercus dilatata (66.7%) and Hedera
      nepalensis (63.3%). Similar behavior was observed in histamine assay with
      percentage inhibitions of 74.3%, 60.4%, and 63.5%, respectively. Antidepressant
      activity was estimated by forced swim test and the most potent activity was
      revealed by Withania coagulans with immobility time 2.2s (95.9%) followed by
      Hedera nepalensis with immobility time 25.3s (53.4%). Moreover, the crude
      extracts of Fagonia cretica (74.6%), Hedera nepalensis (73.8%), and Phytolacca
      latbenia (67.3%) showed good anticoagulant activity with coagulation times 86.9s,
      84.3s, and 67.5s, respectively. Collectively, the results demonstrate that these
      five plants have rich medicinal constituents which can be further explored.

PMID- 29348775
TI  - Testicular Dysfunction Ameliorative Effect of the Methanolic Roots Extracts of
      Maytenus procumbens and Ozoroa paniculosa.
AB  - The traditional use of medicinal plants in the management of sexual dysfunctions
      has a long history. This study investigated testicular dysfunction ameliorative
      effect of the methanolic roots extracts of Maytenus procumbens and Ozoroa
      paniculosa in a butanol-induced testicular dysfunction rat model. The rats in
      respective experimental groups were orally administered with the extract at 50
      and 250 mg/kg bw, daily for 28 days. The cytotoxicity of the extracts was
      evaluated against HEK293, MCF-7, and HT29 cell lines. The extracts exhibited
      moderate (LC50 30.3-330.2 MUg/mL) to weak (LC50 200.8-438.4 MUg/mL) cytotoxicity
      level on the cancer and normal cells, respectively. While relatively lower serum
      testosterone levels and total sperm count along with decreased numbers of
      spermatogonia were noted in the untreated group, all these parameters were
      improved in the groups treated with the extracts at 250 mg/kg. Improved
      histomorphological changes of the testes were also observed when compared to the
      untreated group. While the extracts (at 250 mg/kg) increased serum reduced
      glutathione content and decreased malondialdehyde content, a relatively higher
      serum creatinine level was also observed in the treated animals group. The
      results indicate that the two plant extracts have potential to ameliorate
      testicular dysfunction.

PMID- 29348776
TI  - Effects of the Fruit Extract of Tribulus terrestris on Skin Inflammation in Mice
      with Oxazolone-Induced Atopic Dermatitis through Regulation of Calcium Channels,
      Orai-1 and TRPV3, and Mast Cell Activation.
AB  - Ethnopharmacological Relevance: In this study, we investigated the effects of
      Tribulus terrestris fruit (Leguminosae, Tribuli Fructus, TF) extract on oxazolone
      induced atopic dermatitis in mice. Materials and Methods: TF extract was prepared
      with 30% ethanol as solvent. The 1% TF extract with or without 0.1% HC was
      applied to the back skin daily for 24 days. Results: 1% TF extract with 0.1% HC
      improved AD symptoms and reduced TEWL and symptom scores in AD mice. 1% TF
      extract with 0.1% HC inhibited skin inflammation through decrease in inflammatory
      cells infiltration as well as inhibition of Orai-1 expression in skin tissues. TF
      extract inhibited Orai-1 activity in Orai-1-STIM1 cooverexpressing HEK293T cells
      but increased TRPV3 activity in TRPV3-overexpressing HEK293T cells. TF extract
      decreased beta-hexosaminidase release in RBL-2H3 cells. Conclusions: The present
      study demonstrates that the topical application of TF extract improves skin
      inflammation in AD mice, and the mechanism for this effect appears to be related
      to the modulation of calcium channels and mast cell activation. This outcome
      suggests that the combination of TF and steroids could be a more effective and
      safe approach for AD treatment.

PMID- 29348777
TI  - A Randomized Controlled Study of the Yi Qi Gu Biao Pill in the Treatment of
      Frequent Exacerbator Phenotype in Chronic Obstructive Pulmonary Disease (Lung and
      Spleen Qi Deficiency Syndrome).
AB  - Objective: To evaluate the efficacy and safety of Yi Qi Gu Biao (YQGB) pill in
      treating frequent exacerbator phenotype in chronic obstructive pulmonary disease
      (lung and spleen qi deficiency syndrome) (FEPCOPD). Methods: This prospective,
      randomized, double-blind, controlled study assessed 112 cases (64 included) of
      FEPCOPD treated at the outpatient department in our hospital in January-August
      2016. The patients were randomly divided into YQGB and placebo (Pb) and treated
      for three months. Lung function, CAT, mMRC, and TCM symptom scores (TCMs) were
      observed. Results: Compared with Pb, YQGB showed decreased wheezing symptom
      scores (WSs) and TCMs at one month and decreased CAT and TCMs at three months.
      From one to three months, CAT, cough, sputum, WSs, and TCMs in YQGB were lower
      than pretreatment values. But in Pb, CAT was lower than pretreatment values after
      one month; CAT, sputum, and TCMs were lower than pretreatment values after two
      months; CAT, cough, sputum, WSs, and TCMs were lower than pretreatment values
      after three months. Conclusion: Yi Qi Gu Biao pill can improve wheezing, health
      status, and TCMs in FEPCOPD and also can shorten the durations of cough, sputum,
      and wheezing. This trial is registered in the Clinical Trials Registry of China:
      ChiCTR-IOR-15007542 (on 8 December 2015).

PMID- 29348778
TI  - Marketing health education: advertising margarine and visualising health in
      Britain from 1964-c.2000.
AB  - During the post-war period, margarine was re-conceptualised as a value-added
      product with distinct health benefits. This article contextualises the
      advertising of margarine as a healthy food, focusing on Unilever's Flora brand as
      an important case study in legitimising the emergent role of disease prevention
      as a marketing tool. It uses the methodology of visual culture to examine how
      advertising employed chronic disease prevention as a selling tool. This article
      assesses how the post-war environment gave rise to new ways of visually
      advertising food, and how these promoted innovative visualisations of food, the
      body and their interactions with health.

PMID- 29348779
TI  - Mutual proximity graphs for improved reachability in music recommendation.
AB  - This paper is concerned with the impact of hubness, a general problem of machine
      learning in high-dimensional spaces, on a real-world music recommendation system
      based on visualisation of a k-nearest neighbour (knn) graph. Due to a problem of
      measuring distances in high dimensions, hub objects are recommended over and over
      again while anti-hubs are nonexistent in recommendation lists, resulting in poor
      reachability of the music catalogue. We present mutual proximity graphs, which
      are an alternative to knn and mutual knn graphs, and are able to avoid hub
      vertices having abnormally high connectivity. We show that mutual proximity
      graphs yield much better graph connectivity resulting in improved reachability
      compared to knn graphs, mutual knn graphs and mutual knn graphs enhanced with
      minimum spanning trees, while simultaneously reducing the negative effects of
      hubness.

PMID- 29348781
TI  - Sequential Probability Ratio Testing with Power Projective Base Method Improves
      Decision-Making for BCI.
AB  - Obtaining a fast and reliable decision is an important issue in brain-computer
      interfaces (BCI), particularly in practical real-time applications such as
      wheelchair or neuroprosthetic control. In this study, the EEG signals were
      firstly analyzed with a power projective base method. Then we were applied a
      decision-making model, the sequential probability ratio testing (SPRT), for
      single-trial classification of motor imagery movement events. The unique strength
      of this proposed classification method lies in its accumulative process, which
      increases the discriminative power as more and more evidence is observed over
      time. The properties of the method were illustrated on thirteen subjects'
      recordings from three datasets. Results showed that our proposed power projective
      method outperformed two benchmark methods for every subject. Moreover, with
      sequential classifier, the accuracies across subjects were significantly higher
      than that with nonsequential ones. The average maximum accuracy of the SPRT
      method was 84.1%, as compared with 82.3% accuracy for the sequential Bayesian
      (SB) method. The proposed SPRT method provides an explicit relationship between
      stopping time, thresholds, and error, which is important for balancing the time
      accuracy trade-off. These results suggest SPRT would be useful in speeding up
      decision-making while trading off errors in BCI.

PMID- 29348782
TI  - Adsorption and Desulfurization Mechanism of Thiophene on Layered FeS(001), (011),
      and (111) Surfaces: A Dispersion-Corrected Density Functional Theory Study.
AB  - Layered transition-metal chalcogenides have emerged as a fascinating new class of
      materials for catalysis. Here, we present periodic density functional theory
      (DFT) calculations of the adsorption of thiophene and the direct desulfurization
      reaction pathways on the (001), (011), and (111) surfaces of layered FeS. The
      fundamental aspects of the thiophene adsorption, including the initial adsorption
      geometries, adsorption energies, structural parameters, and electronic
      properties, are presented. From the calculated adsorption energies, we show that
      the flat adsorption geometries, wherein the thiophene molecule forms multiple pi
      bonds with the FeS surfaces, are energetically more favorable than the upright
      adsorption geometries, with the strength of adsorption decreasing in the order
      FeS(111) > FeS(011) > FeS(001). The adsorption of the thiophene onto the reactive
      (011) and (111) surfaces is shown to be characterized by charge transfer from the
      interacting Fe d-band to the pi-system of the thiophene molecule, which causes
      changes of the intramolecular structure including loss of aromaticity and
      elongation of the C-S bonds. The thermodynamic and kinetic analysis of the
      elementary steps involved in the direct desulfurization of thiophene on the
      reactive FeS surfaces is also presented. Direct desulfurization of thiophene
      occurs preferentially on the (111) surface, as reflected by the overall
      exothermic reaction energy calculated for the process (ER = -0.15 eV), with an
      activation energy of 1.58 eV.

PMID- 29348783
TI  - Breast Massage, Implant Displacement, and Prevention of Capsular Contracture
      After Breast Augmentation With Implants: A Review of the Literature.
AB  - Objective: Capsular contracture, the most common complication following breast
      augmentation with implants, is a complex inflammatory reaction that ultimately
      leads to fibrosis at the contact site between the implant and tissue. A number of
      peri-, pre-, and postoperative techniques have been postulated and implemented by
      many surgeons to reduce the incidence of capsular contracture. Breast massage and
      implant displacement technique is a commonly recommended practice that has not
      been well studied in regard to capsular contracture prevention. The authors
      present a review of the literature addressing methods and efficacy of massage and
      implant displacement techniques after breast augmentation. Methods: A literature
      review was performed using PubMed and the Cochrane Collaboration Library for
      primary research articles on breast massage or implant displacement after breast
      augmentation with implants for breast contracture prevention between January 1975
      and March 2017. Exclusion criteria were studies that were focused on the
      treatment rather than prevention of breast contracture, addressed other
      strategies of preventing contracture as the main focus, or did not report the
      number of patients studied. Information related to massage technique and capsular
      contracture outcomes was extracted. Results: The literature search yielded 4
      relevant studies, with a total of 587 patients. Outcomes evaluated included
      massage technique, onset of massage, frequency of massage, and incidence of
      capsular contracture. Breast massage was introduced between 2 days and 2 weeks
      postoperatively, performed twice daily, and lasted from 2 to 5 minutes for each
      breast. Final postoperative follow-up concluded between 6 and 36 months. The
      average capsular contracture rate was similar, 31% (range, 0-35) in the massage
      group versus 40% (range, 30-90) in the nonmassage group. Conclusions: While
      multiple techniques have been proposed and practiced in the prevention of
      capsular contracture, breast massage and implant displacement techniques remain
      controversial. While there is a method to measure adequacy of breast massage
      pressure, it is not widely utilized. The available data do not support breast
      massage to prevent capsular contracture; more studies with standardized
      techniques are needed to better assess the efficacy of breast massage in
      preventing capsular contracture.

PMID- 29348780
TI  - Host factors that influence mother-to-child transmission of HIV-1: genetics,
      coinfections, behavior and nutrition.
AB  - Mother-to-child transmission (MTCT) is the most important mode of HIV-1
      acquisition among infants and children and it can occur in utero, intrapartum and
      postnatally through breastfeeding. Great progress has been made in preventing
      MTCT through use of antiretroviral regimens during gestation, labor/delivery and
      breastfeeding. The mechanisms of MTCT, however, are multifactorial and remain
      incompletely understood. This review focuses on select host factors affecting
      MTCT, in particular genetic factors, coexisting infections, behavioral factors
      and nutrition. Whereas much emphasis has been placed on decreasing maternal HIV-1
      viral load, an important determinant of MTCT, through use of antiretroviral
      agents, complementary focus on overall maternal health is often neglected. By
      addressing coinfections in mothers and infants, improving the mother's
      nutritional status and modifying risky behaviors and practices, not only is
      maternal and child health improved, but a direct benefit in reducing MTCT can be
      derived. The study of genetic variations in susceptibility to HIV-1 infection is
      rapidly evolving, and the future is likely to bring revolutionary changes in HIV
      1 prevention by enhancing natural resistance to infection and by individually
      tailoring pharmacologic regimens.

PMID- 29348784
TI  - Recipient Vessel Selection in Head and Neck Reconstruction.
AB  - Objective: Recipient vessel caliber may be the single most important variable for
      flow to free tissue transfer. We performed cadaveric dissection of the external
      carotid artery and its branches to analyze average diameter in order to determine
      an algorithm for recipient vessel selection in head and neck reconstruction.
      Methods: The external carotid artery and branches were exposed on 3 lightly
      embalmed male human cadavers, aged 82 to 85 years. Each vessel was dissected, and
      luminal diameters were recorded with calipers. Results: The proximal ECA had the
      greatest average diameter (4 +/- 0.6 mm) and potential flow; followed by distal
      ECA (2.85 +/- 0.4 mm) facial (2.0 +/- 0.6 mm), lingual (1.65 +/- 0.6 mm),
      superior thyroid (1 +/- 0.3  mm), and superficial temporal (0.85 +/- 0.4 mm).
      There was a trend towards size variation between sides of the same cadaver.
      Conclusion: The external carotid artery has the greatest internal diameter and
      potential blood flow. It should be considered, when feasible, especially for
      defects of the upper third of the head. For defects of the lower third, the
      facial artery and the lingual artery should be utilized before the smaller
      diameter superior thyroid artery. Vessel selection is more challenging in the
      setting of radiation therapy, complex trauma, and prior neck surgery. In these
      settings, it is useful to have knowledge of the vascular anatomy and an objective
      algorithm for recipient vessel selection.

PMID- 29348785
TI  - New Insights into the Benefits of Polyphenols in Chronic Diseases.

PMID- 29348787
TI  - Oxidative Stress in Metabolic Disorders and Drug-Induced Injury: The Potential
      Role of Nrf2 and PPARs Activators.

PMID- 29348786
TI  - DNA Methylation and the Potential Role of Methyl-Containing Nutrients in
      Cardiovascular Diseases.
AB  - Patients suffering from cardiovascular diseases (CVDs) experience a low quality
      of life and increase pressure on healthcare systems both nationally and globally.
      DNA methylation, which refers to the pathway by which DNA methyltransferase
      facilitates the addition of a methyl group to DNA, is of critical importance in
      this respect primarily because the epigenetic modification is implicated in a
      range of serious conditions including atherosclerosis, CVDs, and cancer. Research
      findings indicate that the number of epigenetic alterations can be elicited (both
      in utero and in adults) through the administration of certain nutritional
      supplements, including folic acid and methionine; this is partly attributable to
      the effect employed by methyl-containing nutrients in DNA methylation. Thus, for
      the purpose of illuminating viable therapeutic measures and preventive strategies
      for CVDs, research should continue to explore the intricate associations that
      exist between epigenetic regulation and CVD pathogenesis. This review centers on
      an exposition of the mechanism by which DNA methylation takes place, the impact
      it has on a range of conditions, and the potential clinical value of nutrition,
      driven mainly by the observation that nutritional supplements such as folic acid
      can affect DNA methylation.

PMID- 29348788
TI  - The Role of Redox-Regulating Enzymes in Inoperable Breast Cancers Treated with
      Neoadjuvant Chemotherapy.
AB  - Although validated predictive factors for breast cancer chemoresistance are
      scarce, there is emerging evidence that the induction of certain redox-regulating
      enzymes may contribute to a poor chemotherapy effect. We investigated the
      possible association between chemoresistance and cellular redox state regulation
      in patients undergoing neoadjuvant chemotherapy (NACT) for breast cancer. In
      total, 53 women with primarily inoperable or inflammatory breast cancer who were
      treated with NACT were included in the study. Pre-NACT core needle biopsies and
      postoperative tumor samples were immunohistochemically stained for nuclear factor
      erythroid 2-related factor 2 (Nrf2), Kelch-like ECH-associated protein 1 (Keap1),
      thioredoxin (Trx), and peroxiredoxin I (Prx I). The expression of all studied
      markers increased during NACT. Higher pre-NACT nuclear Prx I expression predicted
      smaller size of a resected tumor (p = 0.00052; r = -0.550), and higher pre-NACT
      cytoplasmic Prx I expression predicted a lower amount of evacuated nodal
      metastasis (p = 0.0024; r = -0.472). Pre-NACT nuclear Trx expression and pre-NACT
      nuclear Keap1 expression had only a minor prognostic significance as separate
      factors, but when they were combined, low expression for both antibodies before
      NACT predicted dismal disease-free survival (log-rank p = 0.0030). Our results
      suggest that redox-regulating enzymes may serve as potential prognostic factors
      in primarily inoperable breast cancer patients.

PMID- 29348789
TI  - Pretreatment Donors after Circulatory Death with Simvastatin Alleviates Liver
      Ischemia Reperfusion Injury through a KLF2-Dependent Mechanism in Rat.
AB  - Objective: Severe hepatic ischemia reperfusion injury (IRI) can result in poor
      short- and long-term graft outcome after transplantation. The way to improve the
      viability of livers from donors after circulatory death (DCD) is currently
      limited. The aim of the present study was to explore the protective effect of
      simvastatin on DCD livers and investigate the underlying mechanism. Methods: 24
      male rats randomly received simvastatin or its vehicle. 30 min later, rat livers
      were exposed to warm ischemia in situ for 30 min. Livers were removed and cold
      stored in UW solution for 24 h, subsequently reperfused for 60 min with an
      isolated perfused rat liver system. Liver injury was evaluated during and after
      warm reperfusion. Results: Pretreatment of DCD donors with simvastatin
      significantly decreased IRI liver enzyme release, increased bile output and ATP,
      and ameliorated hepatic pathological changes. Simvastatin maintained the
      expression of KLF2 and its protective target genes (eNOS, TM, and HO-1), reduced
      oxidative stress, inhibited innate immune responses and inflammation, and
      increased the expression of Bcl-2/Bax to suppress hepatocyte apoptosis compared
      to DCD control group. Conclusion: Pretreatment of DCD donors with simvastatin
      improves DCD livers' functional recovery probably through a KLF2-dependent
      mechanism. These data suggest that simvastatin may provide a potential benefit
      for clinical DCD liver transplantation.

PMID- 29348790
TI  - Effects of Aging and Tocotrienol-Rich Fraction Supplementation on Brain Arginine
      Metabolism in Rats.
AB  - Accumulating evidence suggests that altered arginine metabolism is involved in
      the aging and neurodegenerative processes. This study sought to determine the
      effects of age and vitamin E supplementation in the form of tocotrienol-rich
      fraction (TRF) on brain arginine metabolism. Male Wistar rats at ages of 3 and 21
      months were supplemented with TRF orally for 3 months prior to the dissection of
      tissue from five brain regions. The tissue concentrations of L-arginine and its
      nine downstream metabolites were quantified using high-performance liquid
      chromatography and liquid chromatography tandem mass spectrometry. We found age
      related alterations in L-arginine metabolites in the chemical- and region
      specific manners. Moreover, TRF supplementation reversed age-associated changes
      in arginine metabolites in the entorhinal cortex and cerebellum. Multiple
      regression analysis revealed a number of significant neurochemical-behavioral
      correlations, indicating the beneficial effects of TRF supplementation on memory
      and motor function.

PMID- 29348791
TI  - Zinc Protects Oxidative Stress-Induced RPE Death by Reducing Mitochondrial Damage
      and Preventing Lysosome Rupture.
AB  - Zinc deficiency is known to increase the risk of the development of age-related
      macular degeneration (AMD), although the underlying mechanism remains poorly
      defined. In this study, we investigated the effect of zinc on retinal pigment
      epithelium (RPE) survival and function under oxidative conditions. Zinc level was
      5.4 MUM in normal culture conditions (DMEM/F12 with 10% FCS) and 1.5 MUM in serum
      free medium (DMEM/F12). Under serum-free culture conditions, the treatment of RPE
      cells with oxidized photoreceptor outer segment (oxPOS) significantly increased
      intracellular ROS production, reduced ATP production, and promoted RPE death
      compared to oxPOS-treated RPE under normal culture condition. Serum deprivation
      also reduced RPE phagocytosis of oxPOS and exacerbated oxidative insult-induced
      cathepsin B release from lysosome, an indicator of lysosome rupture. The addition
      of zinc in the serum-free culture system dose dependently reduced ROS production,
      recovered ATP production, and reduced oxidative stress- (oxPOS- or 4-HNE) induced
      cell death. Zinc supplementation also reduced oxidative stress-mediated cathepsin
      B release in RPE cells. Our results suggest that zinc deficiency sensitizes RPE
      cells to oxidative damage, and zinc supplementation protects RPE cells from
      oxidative stress-induced death by improving mitochondrial function and preventing
      lysosome rupture.

PMID- 29348792
TI  - Coenzyme Q10 Regulates Antioxidative Stress and Autophagy in Acute Myocardial
      Ischemia-Reperfusion Injury.
AB  - Background: Oxidative stress and autophagy both play key roles in continuous
      cardiomyocyte death and cardiac dysfunction after reperfusion therapy for acute
      myocardial ischemia-reperfusion injury. Coenzyme Q10 (CQ10), which is a fat
      soluble quinone antioxidant, is involved in the pathophysiological processes of
      neurodegenerative diseases, cancer, diabetes, heart failure, and other diseases.
      Our objective was to determine if, and by what mechanism, CQ10 can ameliorate
      acute myocardial ischemia-reperfusion injury and improve heart function. Methods
      and Results: Fat-soluble CQ10 in soybean oil solvent was preconditioned in rats
      with acute myocardial ischemia-reperfusion injury by intraperitoneal injection.
      Oxidant and antioxidant levels were compared between the preconditioned and
      control groups. Autophagy was measured by Western blotting analysis of autophagy
      proteins. Proapoptotic proteins and immunofluorescence were used to assess cell
      apoptosis. Infarct size was determined by triphenyl tetrazolium chloride (TTC)
      staining and Evans blue staining and visualized myocardial pathology by tissue
      staining. Finally, we assessed cardiac function by electrocardiography (ECG) and
      hemodynamics. Conclusions: This study reveals that CQ10 preconditioning regulates
      antioxidant levels and the oxidant balance, enhances autophagy, reduces
      myocardial apoptosis and death, and improves cardiac function in rats with acute
      ischemia-reperfusion injury. These results imply that CQ10 protects against acute
      myocardial ischemia-reperfusion injury via the antioxidative stress and autophagy
      pathways.

PMID- 29348794
TI  - Tubby-like protein 1 (Tulp1) is a target of microRNA-134 and is down-regulated in
      experimental epilepsy.
AB  - MicroRNAs are important determinants of gene expression via post-transcriptional
      control of the protein levels of their mRNA targets. MicroRNA-134 (miR-134) has
      emerged as an important brain-specific microRNA which has been implicated in the
      control of dendritic spine morphology, neuronal differentiation and apoptosis.
      Here we show that Tubby-like protein 1 (Tulp1) is a target of miR-134. Tulp1
      protein showed a similar cellular distribution pattern in the hippocampus to miR
      134 and displayed an inverse expression pattern in the mouse retina.
      Bioinformatics analyses identified a conserved miR-134 binding site in the 3'
      untranslated region of both mouse and human Tulp1 and luciferase reporter assays
      confirmed miR-134 targets Tulp1 in vitro. Induction of prolonged seizures in mice
      resulted in upregulation of miR-134 and downregulation of protein levels of Tulp1
      which were reversed in animals injected with locked nucleic acid-modified
      antagomirs targeting miR-134. Finally, knockdown of Tulp1 in human neurons caused
      an increase in vulnerability to excitotoxicity. These data identify Tulp1/TULP1
      as a novel target of miR-134, which may contribute to underlying pathomechanisms
      in epilepsy.

PMID- 29348795
TI  - Therapeutic angiogenesis of exosomes for ischemic stroke.
AB  - Angiogenesis is the process through which new blood vessels are formed, while
      therapeutic angiogenesis aims to promote and control the angiogenic response.
      Ischemia results from the lack of blood flow with oxygen and nutrients.
      Therapeutic angiogenesis is crucial in preserving brain tissue and bodily
      functions after ischemic stroke. Various approaches have been proposed to promote
      angiogenesis in ischemic diseases. Traditional protein/gene and subsequent
      stem/progenitor cell approaches have not shown consistent efficacy for ischemic
      diseases in clinical trials. Exosomes are microparticles secreted from cells and
      conduct cell-cell communication including stem cell or cancer cell induced pro
      angiogenesis. Utilization of exogenous exosomes for the treatment of ischemic
      diseases is an emerging approach which may prevent certain disadvantages such as
      easy degradation and tumor formation happened in other strategies. This review
      highlights recent reports on the use of exosomes as a therapeutic agent to
      promote angiogenesis in ischemic stroke.

PMID- 29348793
TI  - Inflammasome in drug abuse.
AB  - Drug abuse disorders refer to a set of related negative health implications
      associated with compulsive drug seeking and use. Because almost all addictive
      drugs act on the brain, many of them cause neurological impairments after long
      term abuse. Neuropathological studies have revealed a widespread impairment of
      the cellular elements. As the key components to limit the damage of neural cells,
      CNS immune system is also found affected by these drugs, directly or indirectly.
      It has been shown that drugs of abuse alter neuroimmune gene expression and
      signaling. Growing studies on neuroimmune factors further demonstrate their
      indispensable role in drugs-induced neurotoxicity. As an important
      proinflammatory intracellular receptor, inflammasome is activated in many
      neurodegenerative diseases in response to a broad range of damage-associated
      molecular patterns (DAMPs) signals. In the cases of drug abuse, especially in
      those with comorbid of HIV infection and sustained pain, inflammasome activation
      significantly promotes the neuroinflammation-associated toxicities. To understand
      inflammasome in drug-associated neurotoxic activity, we reviewed the role played
      by inflammasome in drug abuse-induced microglial neurotoxicity and evaluated the
      potential of imflammasone as a therapeutic target for drug abuse disorders based
      on recent development of various selective small-molecular inflammasome
      inhibitors.

PMID- 29348796
TI  - Condition-specific transcriptional regulation of neuronal ion channel genes in
      brain ischemia.
AB  - In the context of seeking novel therapeutic targets for treating ischemic stroke,
      the preconditioning ischemia-induced brain ischemic tolerance has been used as a
      model of endogenously operative, broad-based neuroprotective mechanisms.
      Targeting such mechanisms is considered potentially less prone to adverse side
      effects, as those seen in many failed clinical trials that focus on single
      targets using exogenous compounds. Results from previous studies have revealed an
      overall decrease in potassium channel activity in tolerance development. The
      objective of this study is to identify ion channel genes that are differentially
      regulated under different brain ischemic conditions, as a mean to identify those
      ion channels that are associated with ischemic brain injury and ischemic
      tolerance. In mice in vivo, transient focal cerebral ischemia was induced by
      middle cerebral artery occlusion. In cultured neuronal cells in vitro, simulated
      ischemia was modeled by oxygen-glucose deprivation. For both in vivo and in vitro
      studies, three principal ischemic conditions were included: ischemic
      preconditioned, injured and tolerant, respectively, plus appropriate controls. In
      these model systems, transcript levels of a panel of 84 neuronal ion channels
      genes were analyzed with a quantitative real-time PCR mini-array. The results
      showed that, both in vivo and in vitro, there was a predominant down regulation
      in neuronal ion channel genes under ischemic-tolerant conditions, and an up
      regulation in ischemic injury. Similar changes were observed among potassium,
      sodium and calcium channel genes. A number of regulated genes exhibited opposing
      changes under ischemic-injured and ischemic-tolerant conditions. This subset of
      ion channel genes exemplifies potentially novel leads for developing multi
      factorial therapeutic targets for treating ischemic stroke.

PMID- 29348797
TI  - Experimentally-induced ventricular arrhythmias.
AB  - Hypoxia and reoxygenation, ischemia and reperfusion, catecholamine infusion,
      ouabain, sodium pentobarbital and caffeine, can all be used experimentally to
      induce ventricular arrhythmias. According to the Lambeth Convention guidelines
      our experimentally-induced ventricular arrhythmias include but are not limited
      to: ventricular premature beats (VPB), ventricular salvos (VS), ventricular
      bigeminy (VB), nonsustained ventricular tachycardia (VTn), sustained ventricular
      tachycardia (VTs) and ventricular fibrillation (VF, or if the heart is not
      defibrillated, sudden cardiac death). We have studied these arrhythmias in the
      absence and presence of adenosine deaminase, methyl xanthines, and more recently,
      acetaminophen. Our laboratory was the first to discover the anti-arrhythmic
      properties of acetaminophen an analgesic used in Western medicine for more than
      100 years before our publication. We have also identified other cardioprotective
      properties of acetaminophen, and have begun to work out some of the
      cellular/molecular mechanisms. For example, we know that acetaminophen protects
      hypoxic/ischemic cardiac mitochondria, in part, by sustaining function of the
      mitochondrial permeability transition pore (MPTP, a protein involved in
      regulating mitochondrial pH). Acetaminophen also attenuates the actions of matrix
      metalloproteinases that can be harmful to myocardial contractile proteins. Of
      course, like all science, more work is needed to expand on these and related
      topics.

PMID- 29348798
TI  - TRPM7 is a unique target for therapeutic intervention of stroke.
AB  - Ischemic stroke is a leading cause of death and long-term disabilities. The
      current therapy is limited to thrombolysis and mechanical recanalization, which
      have limited success. A better understanding of the mechanisms underlying
      ischemic brain injury is therefore needed for the development of more effective
      interventions. Glutamate receptor-mediated Ca2+ overload and neurotoxicity have
      been well established for decades. However, clinical trials failed to show a
      satisfactory effect with the antagonists of glutamate receptors. Other glutamate
      independent mechanisms, such as activation of acid-sensing ion channels and
      transient receptor potential melastatin 7 (TRPM7), have recently emerged as
      important events responsible for neuronal injury under ischemic conditions. In
      this review, we discuss how TRPM7 channels participate in ischemic brain injury.

PMID- 29348799
TI  - Low-dose ethanol excites lateral habenula neurons projecting to VTA, RMTg, and
      raphe.
AB  - It is unclear how social drinking can contribute to the development of addiction
      in susceptible individuals. However, alcohol's aversive properties are a well
      known factor contributing to its abuse. The lateral habenula (LHb) is a key brain
      structure responding to various aversive stimuli, including those related to
      alcohol. We recently reported that ethanol at 10 mM or less that can be achieved
      by social drinking activates many LHb neurons and drives aversive conditioning.
      The current study sought to identify LHb circuits that are activated by a low
      dose of ethanol using immunohistochemistry and anatomic tracing techniques on
      adult Sprague-Dawley rats. We showed here that an intraperitoneal injection of
      ethanol (0.25 g/kg), resulting in a blood ethanol concentration of 5.6 mM,
      significantly increased the number of cFos immunoreactive (IR) neurons in the
      LHb. Most of the ethanol-activated cFos-IR LHb neurons expressed vGluT2
      (vesicular glutamate transporters 2, a marker of a glutamatergic phenotype).
      These LHb neurons projected to the ventral tegmental area (VTA), rostromedial
      tegmental nucleus (RMTg), and dorsal raphe. Moreover, injections of the
      anterograde tracer AAV-CaMKIIa-eGFP into the lateral hypothalamus produced a
      significant amount of labeled fibers with vGluT2 positive terminals on the
      ethanol-activated LHb cells. These results indicate that the LHb neurons
      stimulated by a low-dose of ethanol project to the VTA, RMTg, and dorsal raphe,
      and receive excitatory projections from the lateral hypothalamus. These
      neurocircuits may play a crucial role in mediating the initial aversive effects
      produced by a low-dose of ethanol.

PMID- 29348800
TI  - Methanolic extract of Cola nitida elicits dose-dependent diuretic, natriuretic
      and kaliuretic activities without causing electrolyte impairment, hepatotoxicity
      and nephrotoxicity in rats.
AB  - Cola nitida (Kolanut) is conventionally used in tropical Africa for the treatment
      of all kinds of ailments such as migraine, morning sickness, metabolic disorders
      etc. However, this study was designed to investigate the diuretic, natriuretic
      and kaliuretic activities of methanolic extract of Cola nitida (MECN) in male
      Wistar rats. Adult male Wistar rats were randomly allotted into control (25 ml/kg
      b.w.), furosemide (20 mg/kg b.w; standard), MECN1 (100 mg/kg), MECN2 (200 mg/kg),
      MECN3 (300 mg/kg), MECN4 (400 mg/kg), MECN5 (500 mg/kg), MECN6 (600 mg/kg) groups
      with n=6. The extract was prepared as previously described and the treatment
      lasted for 14 days. Urine volume and diuretic indices were estimated. Urine
      electrolytes, plasma electrolytes, plasma/renal AST/ALT, plasma creatinine and
      urea were assayed using flame photometry and standard colorimetric method
      respectively.Administration of different doses of C. nitida significantly altered
      body weight gain and water intake but not food intake compared with control
      group. There were significant increases in urine volume and urine electrolytes
      (Na+, K+ and Cl-), a decrease in plasma/renal ALT and AST activities, a decrease
      in plasma creatinine and urea concentration and no alteration in plasma
      electrolytes when compared with control and furosemide-treated groups. Our study
      suggests that MECN elicits diuretic, natriuretic, and kaliuretic activities
      without causing electrolyte impairment, hepatotoxicity and nephrotoxicity. These
      effects are dose-dependent.

PMID- 29348801
TI  - The Attack of the Smart Particles: Should Bacteria Be Afraid?
AB  - A shocking state of affairs; the use of nanoparticles as simple carriers is dead
      and outdated. Stimuli-responsive nanoparticles have emerged as active
      participants in the therapeutic landscape, rather than inert molecule carriers.
      And this time they are here to join the ongoing war against an old enemy:
      bacteria.

PMID- 29348802
TI  - Fluorescent Carbon Nanoparticles in Medicine for Cancer Therapy: An Update.
AB  - In the past few years since our viewpoint on carbon nanoparticles was first
      published in 2013 (Kumar, V.; Toffoli, G.; Rizzolio, F. ACS Med. Chem. Lett.2013,
      4 (11), 1012-1013), a considerable progress has been made in the area of
      synthesis, functionalization, and applications of fluorescent carbon
      nanoparticles (CNPs). This update aims to highlight some key points achieved in
      the last 4 years in the development of CNPs with a particular emphasis on the
      approaches to ameliorate clinical applications of CNPs as therapeutics,
      diagnostics, and theranostics agents.

PMID- 29348803
TI  - Synthesis of a Chloroalkene Dipeptide Isostere-Containing Peptidomimetic and Its
      Biological Application.
AB  - The first rapid and efficient chemical synthesis of a cyclic Arg-Gly-Asp (RGD)
      peptide containing a chloroalkene dipeptide isostere (CADI) is reported. By a
      developed synthetic method, an N-tert-butylsulfonyl protected CADI was obtained
      utilizing diastereoselective allylic alkylation as a key reaction. This CADI was
      also transformed into an N-Fmoc protected CADI in a few steps. The CADI was used
      in Fmoc-based solid-phase peptide synthesis. The first synthesis of a CADI
      containing cyclic RGD peptide was successful, and the synthesized CADI-containing
      peptidomimetic was found to be a more potent inhibitor against integrin-mediated
      cell attachment than the parent cyclic peptide.

PMID- 29348804
TI  - Lysine Analogue of Polymyxin B as a Significant Opportunity for Photodynamic
      Antimicrobial Chemotherapy.
AB  - In order to highlight the potential of photodynamic antimicrobial chemotherapy in
      case of infections by antibiotic resistant-strains, a new antimicrobial peptide
      conjugate has been synthesized, consisting of a derivative of polymyxin B and a
      cationic porphyrin covalently attached together to a spacer. A polymyxin-derived
      moiety was subjected to a primary structural modification in the replacement of
      four diaminobutyrate residues with lysine ones. This modification was done in
      order to strongly reduce bactericidal activity, with the aim to eliminate the
      potential rise of polymyxin-resistant strains. Despite this modification, this
      new conjugate displayed a strong photobactericidal activity against Gram-positive
      as well as Gram-negative bacteria. It was further shown that this conjugate was
      able to strongly stick to the cell walls of either kind of strain, thus helping
      to inactivate bacteria through the production of reactive oxygen species under
      light irradiation.

PMID- 29348805
TI  - Synthesis and SAR of 1,2,3,4-Tetrahydroisoquinoline-Based CXCR4 Antagonists.
AB  - CXCR4 is the most common chemokine receptor expressed on the surface of many
      cancer cell types. In comparison to normal cells, cancer cells overexpress CXCR4,
      which correlates with cancer cell metastasis, angiogenesis, and tumor growth.
      CXCR4 antagonists can potentially diminish the viability of cancer cells by
      interfering with CXCL12-mediated pro-survival signaling and by inhibiting
      chemotaxis. Herein, we describe a series of CXCR4 antagonists that are derived
      from (S)-5,6,7,8-tetrahydroquinolin-8-amine that has prevailed in the literature.
      This series removes the rigidity and chirality of the tetrahydroquinoline
      providing 2-(aminomethyl)pyridine analogs, which are more readily accessible and
      exhibit improved liver microsomal stability. The medicinal chemistry strategy and
      biological properties are described.

PMID- 29348806
TI  - Therapeutic Nanosystem Consisting of Singlet-Oxygen-Responsive Prodrug and
      Photosensitizer Excited by Two-Photon Light.
AB  - Using light as the sole stimulus and employing the generated singlet oxygen as a
      therapeutic agent and the trigger to activate chemo-drug release could serve as
      an elegant way to bring into full play the advantageous features of light and
      enhance therapeutic efficacy through a combination of chemotherapy and
      photodynamic therapy. Herein a liposomal drug system has been developed by
      embedding a fluorescent photosensitizer and a prodrug into phospholipid vesicles.
      Upon one- or two-photon light irradiation, the photosensitizer generates singlet
      oxygen, which removes the protecting group of the prodrug and subsequently causes
      the release of the active drug chlorambucil. With the combined action of O21 and
      chlorambucil, highly controllable cytotoxicity toward cancer cells was achieved.
      In addition, the fluorescent photosensitizer gives out fluorescent signal acting
      as the drug monitoring agent. This strategy may provide an efficient approach for
      cancer treatment and some useful insights for designing light-stimulated on
      demand therapeutic systems.

PMID- 29348807
TI  - Discovery of Spiro Oxazolidinediones as Selective, Orally Bioavailable Inhibitors
      of p300/CBP Histone Acetyltransferases.
AB  - p300 and its paralog CBP can acetylate histones and other proteins and have been
      implicated in a number of diseases characterized by aberrant gene activation,
      such as cancer. A novel, highly selective, orally bioavailable histone
      acetyltransferase (HAT) domain inhibitor has been identified through virtual
      ligand screening and subsequent optimization of a unique hydantoin screening hit.
      Conformational restraint in the form of a spirocyclization followed by
      substitution with a urea led to a significant improvement in potency. Replacement
      of the hydantoin moiety with an oxazolidinedione followed by fluoro substitution
      led to A-485, which exhibits potent cell activity, low clearance, and high oral
      bioavailability.

PMID- 29348808
TI  - Dual NAMPT/HDAC Inhibitors as a New Strategy for Multitargeting Antitumor Drug
      Discovery.
AB  - Novel dual nicotinamide phosphoribosyltransferase (NAMPT) and histone deacetylase
      (HDAC) inhibitors were designed by a pharmacophore fusion approach. The
      thiazolocarboxamide inhibitors were highly active for both targets. In
      particular, compound 7f (NAMPT IC50 = 15 nM, HDAC1 IC50 = 2 nM) showed potent in
      vivo antitumor efficacy in the HCT116 xenograft model. The study offers a new
      strategy for multitarget antitumor drug discovery by simultaneously acting on
      cancer metabolism and epigenetics.

PMID- 29348809
TI  - Discovery of MK-8722: A Systemic, Direct Pan-Activator of AMP-Activated Protein
      Kinase.
AB  - 5'-Adenosine monophosphate-activated protein kinase (AMPK) is a key regulator of
      mammalian energy homeostasis and has been implicated in mediating many of the
      beneficial effects of exercise and weight loss including lipid and glucose
      trafficking. As such, the enzyme has long been of interest as a target for the
      treatment of Type 2 Diabetes Mellitus. We describe the optimization of beta1
      selective, liver-targeted AMPK activators and their evolution into systemic pan
      activators capable of acutely lowering glucose in mouse models. Identifying
      surrogates for the key acid moiety in early generation compounds proved essential
      in improving beta2-activation and in balancing improvements in plasma unbound
      fraction while avoiding liver sequestration.

PMID- 29348810
TI  - Structure-Based Virtual Screening for the Discovery of Novel Inhibitors of New
      Delhi Metallo-beta-lactamase-1.
AB  - Bacterial resistance has become a worldwide concern after the emergence of
      metallo-beta-lactamases (MBLs). They represent one of the major mechanisms of
      bacterial resistance against beta-lactam antibiotics. Among MBLs, New Delhi
      metallo-beta-lactamase-1 NDM-1, the most prevalent type, is extremely efficient
      in inactivating nearly all-available antibiotics including last resort
      carbapenems. No inhibitors for NDM-1 are currently available in therapy, making
      the spread of NDM-1 producing bacterial strains a serious menace. With this
      perspective, we performed a structure-based in silico screening of a commercially
      available library using FLAPdock and identified several, non-beta-lactam
      derivatives as promising candidates active against NDM-1. The binding affinities
      of the highest scoring hits were measured in vitro revealing, for some of them,
      low micromolar affinity toward NDM-1. For the best inhibitors, efficacy against
      resistant bacterial strains overexpressing NDM-1 was validated, confirming their
      favorable synergistic effect in combination with the carbapenem Meropenem.

PMID- 29348811
TI  - Disconnecting the Estrogen Receptor Binding Properties and Antimicrobial
      Properties of Parabens through 3,5-Substitution.
AB  - Commercially utilized parabens are employed for their antimicrobial properties,
      but a weak binding to the estrogen receptor alpha (ERalpha) may lead to breast
      cancer in some applications. Modification of the paraben scaffold should allow
      for a disconnection of these observed properties. Toward this goal, various 3,5
      substituted parabens were synthesized and assessed for antimicrobial properties
      against S. aureus as well as competitive binding to the ERalpha. The minimum
      inhibitory concentration assay confirmed retention of antimicrobial activity in
      many of these derivatives, while all compounds exhibited decreased xenoestrogen
      activity as determined by a combination of competitive enzyme linked
      immunosorbent assay (ELISA), proliferation, and estrogen receptor binding assay.
      Thus, these changes to the paraben scaffold have led to a multitude of paraben
      derivatives with antimicrobial properties up to 16 times more active than the
      parent paraben and that are devoid or significantly diminished of potential
      breast cancer causing properties.

PMID- 29348812
TI  - Design and Synthesis of Isoquinolidinobenzodiazepine Dimers, a Novel Class of
      Antibody-Drug Conjugate Payload.
AB  - Antibody-drug conjugates (ADCs) represent an important class of emerging cancer
      therapeutics. Recent ADC development efforts highlighted the use of
      pyrrolobenzodiazepine (PBD) dimer payload for the treatment of several cancers.
      We identified the isoquinolidinobenzodiazepine (IQB) payload (D211), a new class
      of PBD dimer family of DNA damaging payloads. We have successfully synthesized
      all three IQB stereoisomers, experimentally showed that the purified (S,S)-D211
      isomer is functionally more active than (R,R)-D221 and (S,R)-D231 isomers by
      >50,000-fold and ~200-fold, respectively. We also synthesized a linker-payload
      (D212) that uses (S,S)-D211 payload with a cathepsin cleavable linker, a
      hydrophilic PEG8 spacer, and a thiol reactive maleimide. In addition, homogeneous
      ADCs generated using D212 linker-payload exhibited ideal physicochemical
      properties, and anti-CD33 ADC displayed a robust target-specific potency on AML
      cell lines. These results demonstrate that D212 linker-payload described here can
      be utilized for developing novel ADC therapeutics for targeted cancer therapy.

PMID- 29348813
TI  - Synthesis and Structure-Activity Relationship Study of Biliatresone, a Plant
      Isoflavonoid That Causes Biliary Atresia.
AB  - We report the first synthesis of the plant isoflavonoid biliatresone. The
      convergent synthesis has been applied to the synthesis of several analogs, which
      have facilitated the first structure-activity relationship study for this
      environmental toxin that, on ingestion, recapitulates the phenotype of biliary
      atresia.

PMID- 29348814
TI  - Targeting CD38 alleviates tumor-induced immunosuppression.

PMID- 29348815
TI  - Lysosome-targeting agents in cancer therapy.
AB  - Despite considerable efforts from multiple laboratories worldwide, highly
      specific inhibitors of autophagy for clinical use are not yet available.
      Lysosomal inhibitors are being employed instead, in spite of multiple limitations
      that are summarized herein.

PMID- 29348816
TI  - Development of a predictive miRNA signature for breast cancer risk among high
      risk women.
AB  - Significant limitations exist in our ability to predict breast cancer risk at the
      individual level. Circulating microRNAs (C-miRNAs) have emerged as measurable
      biomarkers (liquid biopsies) for cancer detection. We evaluated the ability of C
      miRNAs to identify women most likely to develop breast cancer by profiling miRNA
      from serum obtained long before diagnosis. 24 breast cancer cases and controls
      (matched for risk and age) were identified from women enrolled in the High-Risk
      Breast Program at the UVM Cancer Center. Isolated RNA from serum was profiled for
      over 2500 human miRNAs. The miRNA expression data were input into a stepwise
      linear regression model to discover a multivariable miRNA signature that predicts
      long-term risk of breast cancer. 25 candidate miRNAs were identified that
      individually classified cases and controls based on statistical methodologies. A
      refined 6-miRNA risk-signature was discovered following regression modeling that
      distinguishes cases and controls (AUC0.896, CI 0.804-0.988) in this cohort. A
      functional relationship between miRNAs that cluster together when cases are
      contrasted against controls was suggested and confirmed by pathway analyses. The
      discovered 6 miRNA risk-signature can discriminate high-risk women who ultimately
      develop breast cancer from those who remain cancer-free, improving current risk
      assessment models. Future studies will focus on functional analysis of the miRNAs
      in this signature and testing in larger cohorts. We propose that the combined
      signature is highly significant for predicting cancer risk, and worthy of further
      screening in larger, independent clinical cohorts.

PMID- 29348817
TI  - A Mitochondrial-targeted purine-based HSP90 antagonist for leukemia therapy.
AB  - Reprogramming of mitochondrial functions sustains tumor growth and may provide
      therapeutic opportunities. Here, we targeted the protein folding environment in
      mitochondria by coupling a purine-based inhibitor of the molecular chaperone Heat
      Shock Protein-90 (Hsp90), PU-H71 to the mitochondrial-targeting moiety,
      triphenylphosphonium (TPP). Binding of PU-H71-TPP to ADP-Hsp90, Hsp90 co
      chaperone complex or mitochondrial Hsp90 homolog, TRAP1 involved hydrogen bonds,
      pi-pi stacking, cation-pi contacts and hydrophobic interactions with the
      surrounding amino acids in the active site. PU-H71-TPP selectively accumulated in
      mitochondria of tumor cells (17-fold increase in mitochondria/cytosol ratio),
      whereas unmodified PU-H71 showed minimal mitochondrial localization. Treatment of
      tumor cells with PU-H71-TPP dissipated mitochondrial membrane potential,
      inhibited oxidative phosphorylation in sensitive cell types, and reduced ATP
      production, resulting in apoptosis and tumor cell killing. Unmodified PU-H71 had
      no effect. Bioinformatics analysis identified a "mitochondrial Hsp90" signature
      in Acute Myeloid Leukemia (AML), which correlates with worse disease outcome.
      Accordingly, inhibition of mitochondrial Hsp90s killed primary and cultured AML
      cells, with minimal effects on normal peripheral blood mononuclear cells. These
      data demonstrate that directing Hsp90 inhibitors with different chemical
      scaffolds to mitochondria is feasible and confers improved anticancer activity. A
      potential "addiction" to mitochondrial Hsp90s may provide a new therapeutic
      target in AML.

PMID- 29348818
TI  - High CYP2E1 activity correlates with hepatofibrogenesis induced by nitrosamines.
AB  - Hepatofibrosis, which leads to cirrhosis and eventual hepatocellular carcinoma,
      is a common response to chronic toxin-mediated liver injury. Nitrosamines are
      potent hepatotoxic agents that cause necrosis and subsequent fibrosis in the
      liver as a result of cytochrome P450 2E1 (CYP2E1)-dependent metabolism, which
      generates toxic metabolites that form adducts with nucleic acids, leading to
      hepatotoxicity and mutagenesis. Herein, CYP2E1 activity and content were
      determined in fibrotic liver tissue from patients with hepatocellular carcinoma.
      The relationship between CYP2E1 innate activity and hepatofibrogenesis was
      evaluated, the effect of inhibition of CYP2E1 activity on hepatofibrosis was
      determined in a Sprague-Dawley rat model of diethylnitrosamine-induced
      hepatofibrosis. The results demonstrated that the CYP2E1 activities in human
      fibrotic tissues are significantly higher than that in normal liver tissues. In
      rats treated with diethylnitrosamine, the livers demonstrated various degree of
      fibrotic changes and collagen deposition in individual rats. The Ishak score,
      which determines the stage of fibrosis, correlated with CYP2E1 innate activity,
      with greater fibrosis in rat livers with higher CYP2E1 innate activity.
      Inhibition of CYP2E1 during diethylnitrosamine treatment decreased hepatofibrosis
      and there was an inverse correlation between the degree of inhibition and the
      extent of hepatofibrosis. Therefore, high CYP2E1 activity is a risk factor for
      hepatofibrogenesis induced by nitrosamines.

PMID- 29348819
TI  - Recombinant protein of Haemonchus contortus small GTPase ADP-ribosylation factor
      1 (HcARF1) modulate the cell mediated immune response in vitro.
AB  - ADP-ribosylation factors (ARFs) are members of the Ras-related small GTPase
      family involved in the vesicular trafficking regulation. Immunomodulatory effects
      of these proteinson host cell arenot being addressed yet. H. contortus small
      GTPase ADP-ribosylation 1 gene (HcARF1) was cloned and recombinant protein of
      HcARF1 (rHcARF1) was successfully expressed in Escherichia coli. Binding activity
      of rHcARF1 to goat PBMCs was confirmed by immunofluorescence assay (IFA) and its
      immunomudulatory effects on cytokine secretion, cell proliferation, cell
      migration and nitric oxide production (NO) were observed by co-incubation of
      rHcARF1. IFA results revealed that rHcARF1 could bind to the PBMCs. The
      interaction of rHcARF1 modulated the cytokine production, the production of IL-4,
      IL-10 and IL-17 was increased in a dose dependent manner, however, the IFN-gamma
      production was significantly decreased. Cell migration and NO production were
      significantly increased by rHcARF1, whereas, rHcARF1 treatment significantly
      suppressed the proliferation of the PBMC in a dose dependent manner. Our findings
      showed that the rHcARF1 play important roles on the goat PBMCs.

PMID- 29348820
TI  - Effects of different cytokines on immune responses of rainbow trout in a virus
      DNA vaccination model.
AB  - Seven rainbow trout cytokine genes (interleukin (IL)-2, IL-8, IL-15, IL-17, IL
      1beta, intracellular interferon (iIFN) 1a, and IFN-gamma2) were evaluated for
      their adjuvant effects on a DNA vaccine, called pG, containing the glycoprotein
      gene of infectious hematopoietic necrosis virus (IHNV). Distinct DNA constructs
      in expression plasmid pcDNA3.1 encoding a cytokine gene were generated.
      Immunofluorescence assays in rainbow trout gonadal cells demonstrated successful
      protein expression from all these constructs. Subsequently, fish were immunized
      with pG alone or together with a cytokine expression plasmid. Results showed that
      each cytokine plasmids at an appropriate dose showed notable effects on immune
      gene expression. IL-17 and IFN-gamma2 can enhance early specific IgM response.
      All cytokines, except IL-8, can benefit initial neutralizing antibody (NAb)
      titers. At 35 days post immunization (dpi), NAb titers of fish immunized with pG
      and IL-2, iIFN1a, or IFN-gamma2 plasmids remained at high levels (1:160). NAb
      titers of fish immunized with pG alone decreased to 1:40. IL-8 or IL-1beta can
      enhance antigen-specific proliferative T-cell responses at 14 dpi. At 28 dpi,
      coinjection of pG with IL-2, IL-8, IL-15, or IL-17 plasmids induced considerably
      stronger lymphocyte proliferation than that with injection of pG alone. All
      cytokine plasmids delivered with pG plasmid enhanced protection of trout against
      IHNV-mediated mortality. These results indicate that the type and dose of trout
      cytokine genes injected into fish affect quality of immune response to DNA
      vaccination.

PMID- 29348821
TI  - Glycan microarray reveal induced IgGs repertoire shift against a dietary
      carbohydrate in response to rabbit anti-human thymocyte therapy.
AB  - Humans have circulating antibodies against diverse glycans containing N
      glycolylneuraminic acid (Neu5Gc) due to function-loss mutation of the CMAH gene.
      This xenogenic non-human carbohydrate is abundant in red meat, xenografts and
      biotherapeutics. Low levels of diet-derived Neu5Gc is also present on normal
      human endothelial cells, and together with anti-Neu5Gc antibodies could
      potentially mediate "xenosialitis" chronic-inflammation. Rabbit anti-human
      thymocyte globulin (ATG) is a drug containing polyclonal IgG glycoproteins
      commonly used as an immunosuppressant in human transplantation and autoimmune
      diseases. In type-1 diabetes patients, infusion of Neu5Gc-glycosylated ATG caused
      increased global anti-Neu5Gc response. Here, for the first time we explore
      changes in anti-Neu5Gc IgG repertoire following the immunization elicited by ATG,
      compared with the basal antibodies repertoire that reflect exposure to dietary
      Neu5Gc. We used glycan microarrays with multiple Neu5Gc-glycans and controls to
      elucidate eventual differences in ATG-elicited repertoire, before/after ATG
      administration and track their kinetics (0, 1, 18 and 24 months). Response of all
      basal-pre-existing Neu5Gc-specific antibodies rapidly increased. This response
      peaked at one month post-ATG, with enhanced affinity, then resolved at 18-24
      months. Induced-antibodies showed expanded diversity and de-novo recognition of
      different Neu5Gc-glycans, including endogenous glycolipids, that was further
      validated by affinity-purified anti-Neu5Gc antibodies from patients' sera. These
      findings strongly suggest that ATG-induced anti-Neu5Gc IgGs represent a secondary
      exposure to this dietary carbohydrate-antigen in humans, with immune memory.
      Given their modified recognition patterns, ATG-evoked anti-Neu5Gc antibodies
      could potentially mediate biological effects different from pre-existing
      antibodies.

PMID- 29348822
TI  - The localization of pre mRNA splicing factor PRPF38B is a novel prognostic
      biomarker that may predict survival benefit of trastuzumab in patients with
      breast cancer overexpressing HER2.
AB  - Cancer biomarkers that can define disease status and provide a prognostic insight
      are essential for the effective management of patients with breast cancer (BC).
      The prevalence, clinicopathological and prognostic significance of PRPF38B
      expression in a consecutive series of 1650 patients with primary invasive breast
      carcinoma were examined using immunohistochemistry. Furthermore, the
      relationship(s) between clinical outcome and PRPF38B expression was explored in
      627 patients with ER-negative (oestrogen receptor) disease, and 322 patients with
      HER2-overexpressing disease. Membranous expression of PRPF38B was observed in
      148/1388 (10.7%) cases and was significantly associated with aggressive
      clinicopathological features, including high grade, high mitotic index,
      pleomorphism, invasive ductal carcinoma of no specific type (IDC-NST), ER
      negative, HER2-overexpression and p53 mutational status (all p < 0.01). In
      patients with ER-negative disease receiving chemotherapy, nuclear expression of
      PRPF38B was significantly associated with a reduced risk of relapse (p = 0.0004),
      whereas membranous PRPF38B expression was significantly associated with increased
      risk of relapse (p = 0.004; respectively) at a 5 year follow-up. When patients
      were stratified according to ER-negative/HER2-positive status, membranous PRPF38B
      expression was associated with a higher risk of relapse in those patients that
      did not receive trastuzumab therapy (p = 0.02), whereas in those patients with ER
      negative/HER2-positive disease that received trastuzumab adjuvant therapy,
      membranous PRPF38B expression associated with a lower risk of relapse (p =
      0.00018). Nuclear expression of PRPF38B is a good prognostic indicator in both ER
      negative patients and ER-negative/HER2-positive BC (breast cancer) patients,
      whereas membranous localisation of PRPF38B is a poor prognostic biomarker that
      predicts survival benefit from trastuzumab therapy in patients with ER
      negative/HER2-overexpressing BC.

PMID- 29348823
TI  - Prevalence of pathogenic germline variants detected by multigene sequencing in
      unselected Japanese patients with ovarian cancer.
AB  - Pathogenic germline BRCA1, BRCA2 (BRCA1/2), and several other gene variants
      predispose women to primary ovarian, fallopian tube, and peritoneal carcinoma
      (OC), although variant frequency and relevance information is scarce in Japanese
      women with OC. Using targeted panel sequencing, we screened 230 unselected
      Japanese women with OC from our hospital-based cohort for pathogenic germline
      variants in 75 or 79 OC-associated genes. Pathogenic variants of 11 genes were
      identified in 41 (17.8%) women: 19 (8.3%; BRCA1), 8 (3.5%; BRCA2), 6 (2.6%;
      mismatch repair genes), 3 (1.3%; RAD51D), 2 (0.9%; ATM), 1 (0.4%; MRE11A), 1
      (FANCC), and 1 (GABRA6). Carriers of BRCA1/2 or any other tested gene pathogenic
      variants were more likely to be diagnosed younger, have first or second-degree
      relatives with OC, and have OC classified as high-grade serous carcinoma (HGSC).
      After adjustment for these variables, all 3 features were independent predictive
      factors for pathogenic variants in any tested genes whereas only the latter two
      remained for variants in BRCA1/2. Our data indicate similar variant prevalence in
      Japanese patients with OC and other ethnic groups and suggest that HGSC and OC
      family history may facilitate genetic predisposition prediction in Japanese
      patients with OC and referring high-risk patients for genetic counseling and
      testing.

PMID- 29348824
TI  - KCa3.1 channel inhibition leads to an ICAM-1 dependent increase of cell-cell
      adhesion between A549 lung cancer and HMEC-1 endothelial cells.
AB  - Early metastasis leads to poor prognosis of lung cancer patients, whose 5-year
      survival rate is only 15%. We could recently show that the Ca2+ sensitive K+
      channel KCa3.1 promotes aggressive behavior of non-small cell lung cancer (NSCLC)
      cells and that it can serve as a prognostic marker in NSCLC. Since NSCLC patients
      die of metastases, we investigated whether KCa3.1 channels contribute to poor
      patient prognosis by regulating distinct steps of the metastatic cascade. We
      investigated the extravasation of NSCLC cells and focused on their adhesion to
      endothelial cells and on transendothelial migration. We quantified the adhesion
      forces between NSCLC cells and endothelial cells by applying single cell force
      spectroscopy, and we monitored transendothelial migration using live-cell
      imaging. Inhibition of KCa3.1 channels with senicapoc or KCa3.1 silencing
      increases the adhesion force of A549 lung cancer cells to human microvascular
      endothelial cells (HMEC-1). Western blotting, immunofluorescence staining and
      biotinylation assays indicate that the elevated adhesion force is due to
      increased expression of ICAM-1 in both cell lines when KCa3.1 channels are
      downregulated. Consistent with this interpretation, an anti-ICAM-1 blocking
      antibody abolishes the KCa3.1-dependent increase in adhesion. Senicapoc inhibits
      transendothelial migration of A549 cells by 50%. Selectively silencing KCa3.1
      channels in either NSCLC or endothelial cells reveals that transendothelial
      migration depends predominantly on endothelial KCa3.1 channels. In conclusion,
      our findings disclose a novel function of KCa3.1 channels in cancer. KCa3.1
      channels regulate ICAM-1 dependent cell-cell adhesion between endothelial and
      cancer cells that affects the transmigration step of the metastatic cascade.

PMID- 29348825
TI  - A novel anti-CD146 antibody specifically targets cancer cells by internalizing
      the molecule.
AB  - CD146 is an adhesion molecule present on many tumors (melanoma, kidney, pancreas,
      breast, ...). In addition, it has been shown to be expressed on vascular
      endothelial and smooth muscle cells. Generating an antibody able to specifically
      recognize CD146 in cancer cells (designated as tumor CD146), but not in normal
      cells, would thus be of major interest for targeting tumor CD146 without
      affecting the vascular system. We thus generated antibodies against the
      extracellular domain of the molecule produced in cancer cells and selected an
      antibody that specifically recognizes tumor CD146. This antibody (TsCD146 mAb)
      was able to detect CD146-positive tumors in human biopsies and in vivo, by PET
      imaging, in a murine xenograft model. In addition, TsCD146 mAb antibody was able
      to specifically detect CD146-positive cancer microparticles in the plasma of
      patients. TsCD146 mAb displayed also therapeutic effects since it was able to
      reduce the growth of human CD146-positive cancer cells xenografted in nude mice.
      This effect was due to a decrease in the proliferation and an increase in the
      apoptosis of CD146-positive cancer cells after TsCD146-mediated internalization
      of the cell surface CD146. Thus, TsCD146 mAb could be of major interest for
      diagnostic and therapeutic strategies against CD146-positive tumors in a context
      of personalized medicine.

PMID- 29348826
TI  - Interaction of macrophages with apoptotic cells inhibits transdifferentiation and
      invasion of lung fibroblasts.
AB  - The invasion of activated fibroblasts is a key mechanism of tissue fibrosis
      pathology. The recognition and uptake of apoptotic cells can induce the anti
      fibrogenic programming of macrophages. We demonstrate that after interacting with
      apoptotic cells, macrophages secrete bioactive molecules that antagonize TGF
      beta1-induced increases in myofibroblast (fibroproliferative) phenotypic markers
      and reduce the enhanced invasive capacity of TGF-beta1- or EGF-treated mouse lung
      fibroblasts (MLg). Furthermore, numerous treatment strategies prevented the anti
      fibrotic effects of conditioned media, including transfection of macrophages with
      COX-2 or RhoA siRNAs or treatment of MLg cells with receptor antagonists for
      prostaglandin E2 (PGE2), PGD2, or hepatocyte growth factor (HGF). Additionally,
      administration of apoptotic cells in vivo inhibited the bleomycin-mediated
      invasive capacity of primary fibroblasts, as well as adhesion and extracellular
      matrix protein mRNA expression. These data suggest that the anti-fibrogenic
      programming of macrophages by apoptotic cells can be used as a novel tool to
      control the progressive fibrotic reaction.

PMID- 29348827
TI  - Molecular-genetic profiling and high-throughput in vitro drug screening in NUT
      midline carcinoma-an aggressive and fatal disease.
AB  - NUT midline carcinoma (NMC) is a rare and aggressive cancer, with survival
      typically less than seven months, that can arise in people of any age.
      Genetically, NMC is defined by the chromosomal fusion of NUTM1 with a chromatin
      binding partner, typically the bromodomain-containing protein BRD4. However,
      little is known about other genetic aberrations in this disease. In this study,
      we used a unique panel of cell lines to describe the molecular-genetic features
      of NMC. Next-generation sequencing identified a recurring high-impact mutation in
      the DNA-helicase gene RECQL5 in 75% of lines studied, and biological signals from
      mutation-signature and network analyses consistent with a general failure in DNA
      repair. A high-throughput drug screen confirmed that microtubule inhibitors,
      topoisomerase inhibitors and anthracyclines are highly cytotoxic in the majority
      of NMC lines, and that cell lines expressing the BRD4-NUTM1 (exon11:exon2)
      variant are an order of magnitude more responsive to bromodomain inhibitors
      (iBETs) on average than those with other BRD4-NUTM1 translocation variants. We
      also identified a highly significant correlation between iBET and aurora kinase
      inhibitor efficacy in this study. Integration of exome sequencing, transcriptome,
      and drug sensitivity profiles suggested that aberrant activity of the nuclear
      receptor co-activator NCOA3 may correlate with poor response to iBETs. In
      conclusion, our data emphasize the heterogeneity of NMC and highlights genetic
      aberrations that could be explored to improve therapeutic strategies. The novel
      finding of a recurring RECQL5 mutation, together with recent reports of
      chromoplexy in this disease, suggests that DNA-repair pathways are likely to play
      a central role in NMC tumorigenesis.

PMID- 29348828
TI  - Dose escalation by image-guided intensity-modulated radiotherapy leads to an
      increase in pain relief for spinal metastases: a comparison study with a regimen
      of 30 Gy in 10 fractions.
AB  - Purpose: Under the existing condition that the optimum radiotherapy regimen for
      spinal metastases is controversial, this study investigates the benefits of dose
      escalation by image-guided intensity-modulated radiotherapy (IG-IMRT) with 60-66
      Gy in 20-30 fractions for spinal metastases. Results: In the dose-escalation
      group, each D50 of planning gross tumor volume (PGTV) was above 60 Gy and each
      Dmax of spinal cord planning organ at risk volume (PRV) was below 48 Gy. The
      median biological effective dose (BED) of Dmax of spinal cord was lower in the
      dose-escalation group compared with that in the 30-Gy group (69.70 Gy vs. 83.16
      Gy, p < 0.001). After one month and three months of the radiotherapy, pain
      responses were better in the dose-escalation group than those in the 30-Gy group
      (p = 0.005 and p = 0.024), and the complete pain relief rates were respectively
      73.69% and 34.29% (p = 0.006), 73.69% and 41.38% (p = 0.028) in two compared
      groups. In the dose-escalation group, there is a trend of a longer duration of
      pain relief, a longer overall survival and a lower incidence of acute radiation
      toxicities. No late radiation toxicities were observed in both groups. Materials
      and Methods: Dosimetric parameters and clinical outcomes, including pain
      response, duration of pain relief, radiation toxicities and overall survival,
      were compared among twenty-five metastatic spinal lesions irradiated with the
      dose-escalation regimen and among forty-four lesions treated with the 30-Gy
      regimen. Conclusions: Conventionally-fractionated IG-IMRT for spinal metastases
      could escalate dose to the vertebral lesions while sparing the spinal cord,
      achieving a better pain relief without increasing radiation complications.

PMID- 29348829
TI  - Roflumilast restores cAMP/PKA/CREB signaling axis for FtMt-mediated tumor
      inhibition of ovarian cancer.
AB  - The abrogation of cAMP generation by overexpression of PDE isoforms promotes the
      inflammatory pathology, and the PDE inhibitors have showed the potential anti
      inflammation effects in clinical. However, the function of PDE inhibitors in
      cancer treatment remains unclear. We here investigated the role of PDE4 inhibitor
      Roflumilast in the treatment of ovarian cancer. We found that Roflumilast could
      effectively inhibit the proliferation, and induce apoptosis and cell cycle arrest
      in two ovarian cancer cell lines OVCAR3 and SKOV3. Meanwhile, the cAMP/PKA/CREB
      signals was activated by Roflumilast, which was accompanied by the up-regulation
      of mitochondrial ferritin (FtMt) level. Interestingly, forced expression of FtMt
      in ovarian cancer enhanced the apoptosis and inhibited tumor growth and the PKA
      inhibitor H89 and knockdown of CREB significantly repressed the expression of
      FtMt to restore the tumor proliferation and inhibit apoptosis. In addition, we
      found that Roflumilast-induced phosphorylated CREB directly promoted
      transcription of FtMt, indicating that Roflumilast up-regulated the expression of
      FtMt in ovarian cancer via cAMP/PKA/CREB signals. The anti-tumor role of
      Roflumilast in vivo was also demonstrated, the treatment of roflumilast
      effectively inhibited tumor proliferation and elevated the FtMt expression to
      restrict the tumor growth via the activation of cAMP/PKA/CREB signals in ovarian
      cancer.

PMID- 29348830
TI  - Inactivation/deficiency of DHODH induces cell cycle arrest and programed cell
      death in melanoma.
AB  - Malignant melanoma (MM) is one of the most malignant tumors and has a very poor
      prognosis. However, there are no effective drugs to treat this disease. As a kind
      of iron flavin dependent enzyme, dihydroorotate dehydrogenase (DHODH, EC 1.3.3.1)
      is the fourth and a key enzyme in the de novo biosynthesis of pyrimidines.
      Herein, we found that DHODH inactivation/deficiency inhibited melanoma cell
      proliferation, induced cell cycle arrest at S phase and lead to autophagy in
      human melanoma cells. Meanwhile, leflunomide treatment induced cell apoptosis and
      deficiency of DHODH sensitized cells to drug-induced apoptosis in BCL-2 deficient
      melanoma cells, while not in BCL-2 abundant melanoma cells. Then we found that
      BCL-2 could rescue apoptosis induced by DHODH inactivation/deficiency. Moreover,
      BCL-2 also showed to promote cell cycle arrest and to inhibit autophagy induced
      by leflunomide. To explore the mechanisms underlying autophagy induced by DHODH
      inhibition, we found that AMPK-Ulk1 axis was activated in this process. Besides,
      JNK was phosphorylated and activated to phosphorylate BCL-2, which abrogated the
      interaction between BCL-2 and Beclin1 and then abolished autophagy. Our findings
      provided evidences for the potential of DHODH used as a drug target for melanoma
      treatment.

PMID- 29348831
TI  - Aberrant expression of miR-21, miR-376c and miR-145 and their target host genes
      in Merkel cell polyomavirus-positive non-small cell lung cancer.
AB  - Merkel Cell Polyoma Virus (MCPyV) infection has been associated with non-small
      cell lung cancer (NSCLC). Viruses can manipulate cellular miRNAs or have a
      profound impact on cellular miRNA expression to control host regulatory pathways.
      In this study, we evaluated the expression profiles of cancer-associated and
      virally affected host microRNAs miR-21, miR-145, miR-146a, miR-155, miR-302c, miR
      367 and miR-376c in a series of NSCLC tissue samples as well as in samples from
      "healthy" sites, distant from the tumour region that were either positive or
      negative for MCPyV DNA. miR-21 and miR-376c were significantly upregulated
      whereas miR-145 was significantly downregulated in the MCPyV+ve samples compared
      to the MCPyV-ve tumour samples. Overall, miR-21 and miR-376c expression was
      higher in tumour compared to healthy tissue samples. No association was observed
      between the miR-155, miR-146a, miR-302c and miR-367 levels and the presence of
      MCPyV. The expression of miR-21 target genes (Pten, Bcl-2, Daxx, Pkr, Timp3), miR
      376c (Grb2, Alk7, Mmp9) and miR-145 (Oct-4, Sox2, Fascin1) and their associated
      pathways (Braf, Akt-1, Akt-2, Bax, Hif1a, p53) was altered between MCPyV+ve tumor
      samples and their corresponding controls. These results show a novel association
      between miR-21, miR-376c and miR-145 and their host target genes with the
      presence of MCPyV, suggesting a mechanism of virus-specific microRNA signature in
      NSCLC.

PMID- 29348832
TI  - Clinical and histological features of primary testicular diffuse large B-cell
      lymphoma: a single center experience in China.
AB  - Primary testicular lymphoma (PTL) is a rare and aggressive form of extranodal
      lymphoma. Approximately 80-98% of PTLs are diffuse large B-cell lymphoma (PT
      DLBCL). The prognosis of DLBCL patients has improved with the addition of
      rituximab to systemic chemotherapy, but outcomes of PT-DLBCL remain poor. This
      may be explained by the high rate of relapse in the central nervous system (CNS)
      and contralateral testis. We analyzed 1,132 newly diagnosed DLBCL patients (37
      with PT-DLBCL) who were treated at our hospital between January 2009 and December
      2014. Twenty-five patients finished follow-up. We analyzed clinical
      characteristics, response to chemotherapy, overall survival, and relapse in the
      CNS and contralateral testis. All patients underwent orchiectomy. The median age
      was 60 (range: 43-82) years. Eleven patients had stage III/IV disease. Five
      patients experienced CNS relapse, and three experienced relapse in the
      contralateral testis. Median overall survival (OS) was not reached at the time of
      reporting. The 3-year OS rate was 57%. None of the nine patients who received
      radiotherapy to the contralateral testis experienced relapse in that location.
      Intrathecal prophylaxis did not reduce the risk of CNS relapse. All five patients
      who experienced CNS relapse had the germinal center B-cell-like subtype of DLBCL.

PMID- 29348833
TI  - Gold nanoparticles as a potent radiosensitizer in neutron therapy.
AB  - The purpose of this study was to investigate the potential of gold nanoparticles
      as radiosensitizer for use in neutron therapy against hepatocellular carcinoma.
      The hepatocellular carcinoma cells lines Huh7 and HepG2 were irradiated with
      gamma and neutron radiation in the presence or absence of gold nanoparticles.
      Effects were evaluated by transmission electron microscopy, cell survival, cell
      cycle, DNA damage, migration, and invasiveness. Gold nanoparticles significantly
      enhanced the radiosensitivity of Huh7 and HepG2 cells to gamma-rays by 1.41- and
      1.16-fold, respectively, and by 1.80- and 1.35-fold to neutron radiation, which
      has high linear energy transfer. Accordingly, exposure to neutron radiation in
      the presence of gold nanoparticles induced cell cycle arrest, DNA damage, and
      cell death to a significantly higher extent, and suppressed cell migration and
      invasiveness more robustly. These effects are presumably due to the ability of
      gold nanoparticles to amplify the effective dose from neutron radiation more
      efficiently. The data suggest that gold nanoparticles may be clinically useful in
      combination therapy against hepatocellular carcinoma by enhancing the toxicity of
      radiation with high linear energy transfer.

PMID- 29348835
TI  - Simultaneous quantification of DNA damage and mitochondrial copy number by long
      run DNA-damage quantification (LORD-Q).
AB  - DNA damage and changes in the mitochondrial DNA content have been implicated in
      ageing and cancer development. To prevent genomic instability and tumorigenesis,
      cells must maintain the integrity of their nuclear and mitochondrial DNA.
      Advances in the research of DNA damage protection and genomic stability, however,
      also depend on the availability of techniques that can reliably quantify
      alterations of mitochondrial DNA copy numbers and DNA lesions in an accurate high
      throughput manner. Unfortunately, no such method has been established yet. Here,
      we describe the high-sensitivity long-run real-time PCR technique for DNA-damage
      quantification (LORD-Q) and its suitability to simultaneously measure DNA damage
      rates and mitochondrial DNA copy numbers in cultured cells and tissue samples.
      Using the LORD-Q multiplex assay, we exemplarily show that the mitochondrial DNA
      content does not directly affect DNA damage susceptibility, but influences the
      efficacy of certain anticancer drugs. Hence, LORD-Q provides a fast and precise
      method to assess DNA lesions, DNA repair and mtDNA replication as well as their
      role in a variety of pathological settings.

PMID- 29348834
TI  - Activity strengths of cortical glutamatergic and GABAergic neurons are correlated
      with transgenerational inheritance of learning ability.
AB  - The capabilities of learning and memory in parents are presumably transmitted to
      their offsprings, in which genetic codes and epigenetic regulations are thought
      as molecular bases. As neural plasticity occurs during memory formation as
      cellular mechanism, we aim to examine the correlation of activity strengths at
      cortical glutamatergic and GABAergic neurons to the transgenerational inheritance
      of learning ability. In a mouse model of associative learning, paired whisker and
      odor stimulations led to odorant-induced whisker motion, whose onset appeared
      fast (high learning efficiency, HLE) or slow (low learning efficiency, LLE). HLE
      male and female mice, HLE female and LLE male mice as well as HLE male and LLE
      female mice were cross-mated to have their first generation of offsprings,
      filials (F1). The onset of odorant-induced whisker motion appeared a sequence of
      high-to-low efficiency in three groups of F1 mice that were from HLE male and
      female mice, HLE female and LLE male mice as well as HLE male and LLE female
      mice. Activities related to glutamatergic neurons in barrel cortices appeared a
      sequence of high-to-low strength in these F1 mice from HLE male and female mice,
      HLE female and LLE male mice as well as HLE male and LLE female mice. Activities
      related to GABAergic neurons in barrel cortices appeared a sequence of low-to
      high strength in these F1 mice from HLE male and female mice, HLE female and LLE
      male mice as well as HLE male and LLE female mice. Neuronal activity strength was
      linearly correlated to learning efficiency among three groups. Thus, the
      coordinated activities at glutamatergic and GABAergic neurons may constitute the
      cellular basis for the transgenerational inheritance of learning ability.

PMID- 29348836
TI  - Vitexin confers HSF-1 mediated autophagic cell death by activating JNK and ApoL1
      in colorectal carcinoma cells.
AB  - Heat shock transcription factor-1 (HSF-1) guards the cancerous cells proteome
      against the alterations in protein homeostasis generated by their hostile tumor
      microenvironment. Contrasting with the classical induction of heat shock
      proteins, the pro-oncogenic activities of HSF-1 remains to be explored.
      Therefore, cancer's fragile proteostatic pathway governed by HSF-1 could be a
      potential therapeutic target and novel biomarker by natural compounds. Vitexin, a
      natural flavonoid has been documented as a potent anti-tumor agent on various
      cell lines. However, in the present study, when human colorectal carcinoma HCT
      116 cells were exposed to vitexin, the induction of HSF-1 downstream target
      proteins, such as heat shock proteins were suppressed. We identified HSF-1 as a
      potential molecular target of vitexin that interact with DNA-binding domain of
      HSF-1, which inhibited HSF-1 oligomerization and activation (in silico).
      Consequently, HSF-1 hyperphosphorylation mediated by JNK operation causes
      transcriptional inactivation of HSF-1, and supported ROS-mediated autophagy
      induction. Interestingly, in HSF-1 immunoprecipitated and silenced HCT-116 cells,
      co-expression of apolipoprotein 1 (ApoL1) and JNK was observed which promoted the
      caspase independent autophagic cell death accompanied by p62 downregulation and
      increased LC3-I to LC3-II conversion. Finally, in vivo findings confirmed that
      vitexin suppressed tumor growth through activation of autophagic cascade in HCT
      116 xenograft model. Taken together, our study insights a probable novel
      association between HSF-1 and ApoL-1 was established in this study, which
      supports HSF-1 as a potential target of vitexin to improve treatment outcome in
      colorectal cancer.

PMID- 29348837
TI  - Combined surgery and radiation improves survival of tonsil squamous cell cancers.
AB  - Objective: The study evaluated the addition of surgery (S) to radiation (RT) on
      survival of squamous cell carcinomas (SCC) of tonsillar-fossa (TF) in a modern
      cohort with similar epidemiology and treatment as current patients. Study Design:
      Retrospective analysis utilizing Surveillance, Epidemiology, and End Results
      (SEER) Program data. Results: For all stages combined TF patients who received
      S+RT had superior OS (p < 0.01) and DSS (p < 0.01). For each stage OS and DSS was
      superior for S+RT (p < 0.05). In multivariate analysis, HRs for OS were
      statistically significantly higher for TF patients (stage 2, 3, and 4) receiving
      RT alone (p < 0.001). Materials and Methods: TF SCC patients treated with either
      S+RT or RT alone between 2004 and 2011 were examined (n = 6,476). Primary outcome
      measures included overall survival (OS) and disease specific survival (DSS). Cox
      proportional hazard ratios (HR) were estimated for patients treated with S+RT
      compared to RT alone. Conclusions: OS and DSS were superior for all stages
      combined and for stages 2, 3, and 4 in TF patients who received S+RT compared to
      RT alone.

PMID- 29348838
TI  - Single nucleotide polymorphisms in ZNF208 are associated with increased risk for
      HBV in Chinese people.
AB  - Single nucleotide polymorphisms (SNPs) in ZNF208 may be associated with
      susceptibility to Hepatitis B virus (HBV). In the current study, we analyzed the
      association between ZNF208 SNPs and risk of HBV in 242 HBV patients and 300
      healthy subjects from the Xi'an area of Chinese Han Population. Of the five SNPs
      examined, rs2188971 (OR: 1.36, 95% CI: 1.04-1.76, P = 0.022), rs8103163 (OR:
      1.40, 95% CI: 1.08-1.82, P = 0.010) and rs7248488 (OR: 1.38, 95% CI: 1.07-1.79, P
      = 0.014) were correlated with HBV susceptibility based on Chi-square tests. After
      the P-values were adjusted by Bonferroni correction, there only rs8103163 (P =
      0.050) was slightly with increased HBV risk. Additionally, haplotype
      Ars2188972Trs2188971Ars8103163Ars7248488 (OR = 1.42; 95% C I, 1.10-1.85; P =
      0.008) was found to increase susceptibility of suffering from HBV. These findings
      suggest that ZNF208 polymorphisms may contribute to the development of HBV.

PMID- 29348839
TI  - Differences in the expression of long noncoding RNAs at different time points in
      the PTSD-like syndrome rat hippocampus.
AB  - The aim of this study was to characterize the expression profiles at different
      time points in the PTSD-like syndrome rat hippocampus and perform analyses. PTSD
      rat models were made as reported by Rau, and we collected the hippocampus at
      different time points. The lncRNAs at different time points were compared by
      microarray and listed. We used quantitative real-time PCR to confirm the lncRNA
      profiling expression data. Bioinformatics analysis was performed on EU056364_P1.
      Compare with control, a total of 948 lncRNAs and 2514 mRNAs were found (fold
      change > 2.0) among the four time points. Additionally, bioinformatics analysis
      of EU056364_P1 suggested it might be involved in memory development through the
      target gene Camk2a.This study revealed different lncRNAs expressed at different
      time points in PTSD and explored the targets of PTSD.

PMID- 29348840
TI  - The prevalence of and risk factors for diabetes mellitus and impaired glucose
      tolerance among Tibetans in China: a cross-sectional study.
AB  - The prevalence of diabetes mellitus (DM) and impaired glucose tolerance (IGT) has
      increased worldwide, although their prevalence and determinants among Tibetans
      are currently unknown. We thus aimed to explore the prevalence of and risk
      factors for DM and IGT among Tibetans in China. In 2011, 1659 Tibetan adults
      (aged >= 18 years) from Changdu, China, were recruited to this cross-sectional
      study. They completed a questionnaire and underwent physical examinations and
      laboratory testing to assess risk factors for DM and IGT. The age-standardized
      prevalence of DM and IGT among Tibetans was 6.2% and 19.7%, respectively. A
      higher annual family income, alcohol consumption, and higher fasting plasma
      glucose (FPG) level were risk factors for DM, with odds ratio (ORs) and 95%
      confidence intervals (CIs) of 3.48 (1.43-8.48; P = 0.006) for those with family
      incomes of > 1600 USD/year, 3.06 (1.31-7.17; P = 0.010) for alcohol consumption,
      and 13.99 (7.76-25.22; P < 0.001) for FPG level. However, altitude was found to
      be negatively associated with the risk of DM; compared to individuals living at <
      3500 meters, the risk of DM decreased by 65% for those living at 3500-3999 meters
      (P = 0.034) and by 89% for those living at >= 4000 meters (P = 0.015). Age, FPG
      levels, and low-density lipoprotein cholesterol levels were significantly
      associated with IGT among Tibetans aged >= 18 years. These findings suggest that
      the prevalence of DM in Tibetans may continue to increase in future decades
      following rapid economic development, and it is crucial to address the management
      of conventional risk factors for reducing the disease burden of DM among
      Tibetans.

PMID- 29348841
TI  - Activation of AMPK by OSU53 protects spinal cord neurons from oxidative stress.
AB  - The present study tested the potential effect of OSU53, a novel AMPK activator,
      against hydrogen peroxide (H2O2)-induced spinal cord neuron damages. Treatment
      with OSU53 attenuated H2O2-induced death and apoptosis of primary murine spinal
      cord neurons. OSU53 activated AMPK signaling, which is required for its actions
      in spinal cord neurons. The AMPK inhibitor Compound C or AMPKalpha1 siRNA almost
      abolished OSU53-mediated neuroprotection against H2O2. On the other hand,
      sustained-activation of AMPK by introducing the constitutive-active AMPKalpha1
      mimicked OSU53's actions, and protected spinal cord neurons from oxidative
      stress. OSU53 significantly attenuated H2O2-induced reactive oxygen species
      production, lipid peroxidation and DNA damages in spinal cord neurons.
      Additionally, OSU53 increased NADPH content and heme oxygenase-1 mRNA expression
      in H2O2-treated spinal cord neurons. Together, we indicate that targeted
      activation of AMPK by OSU53 protects spinal cord neurons from oxidative stress.

PMID- 29348842
TI  - DDEFL1 correlated with Rho GTPases activity in breast cancer.
AB  - DDEFL1 is related to maintaining a limiting amount of ARF6 in GTP-loaded form by
      accelerating its GTP hydrolysis activity, which has been implicated in
      hepatocellular cancer pathogenesis and lung cancer development. We investigated
      DDEFL1 expression in breast cancer and paired normal breast tissues by
      immunohistochemistry and found that DDEFL1 expression was significantly
      associated with tumor size, lymph node metastasis, high content of elastosis and
      TNM stage but not with menopausal status or age. We detected the mRNA and protein
      expression of DDEFL1 in breast cancer cell lines by Western blotting and
      quantitative real-time PCR (qRT-PCR). DDEFL1 was obvious in MDA-MB-435s and MDA
      MB-231 but very weak in ZR-75-1. Further experiments were conducted to evaluate
      the effect of DDEFL1 small interfering RNA (siRNA) transfection on the biological
      behavior of MDA-MB-231. After transfection, the effects of DDEFL1 inhibition on
      expression of mRNA and protein were also analyzed by Western blotting and qRT
      PCR. Increased apoptosis and invasive ability, decreased cellular proliferation
      was found in MDA-MB-231 with successful DDEFL1 siRNA transient transfection (p <
      0.05). Western blotting and qRT-PCR results showed that the DDEFL1 inhibition up
      regulated Caspase-3, Apaf-1, cytochrome c, and Bax expression and down-regulated
      Bcl-2 expression. The DDEFL1 inhibition also down-regulated the mRNA and protein
      expression of Rho, CDC42 and Rac1. Our study provided a functional linkage
      through DDEFL1 with breast cancer biological behaviours by Rho GTPases. Possible
      implication of our main finding for the DDEFL1 role in breast cancer and the
      downstream signaling pathways for the treatment of breast cancer.

PMID- 29348843
TI  - Actein induces autophagy and apoptosis in human bladder cancer by potentiating
      ROS/JNK and inhibiting AKT pathways.
AB  - Human bladder cancer is a common genitourinary malignant cancer worldwide.
      However, new therapeutic strategies are required to overcome its stagnated
      survival rate. Triterpene glycoside Actein (ACT), extracted from the herb black
      cohosh, suppresses the growth of human breast cancer cells. Our study attempted
      to explore the role of ACT in human bladder cancer cell growth and to reveal the
      underlying molecular mechanisms. We found that ACT significantly impeded the
      bladder cancer cell proliferation via induction of G2/M cycle arrest.
      Additionally, ACT administration triggered autophagy and apoptosis in bladder
      cancer cells, proved by the autophagosome formation, LC3B-II accumulation,
      improved cleavage of Caspases/poly (ADP-ribose) polymerase (PARP). Furthermore,
      reduction of reactive oxygen species (ROS) and p-c-Jun N-terminal kinase (JNK)
      could markedly reverse ACT-induced autophagy and apoptosis. In contrast, AKT and
      mammalian target of rapamycin (mTOR) were greatly de-phosphorylated by ACT, while
      suppressing AKT and mTOR activity could enhance the effects of ACT on apoptosis
      and autophagy induction. In vivo, ACT reduced the tumor growth with little
      toxicity. Taken together, our findings indicated that ACT suppressed cell
      proliferation, induced autophagy and apoptosis through promoting ROS/JNK
      activation, and blunting AKT pathway in human bladder cancer, which indicated
      that ACT might be an effective candidate against human bladder cancer in future.

PMID- 29348844
TI  - Trends and variations in mantle cell lymphoma incidence from 1995 to 2013: A
      comparative study between Texas and National SEER areas.
AB  - Background: Few studies have assessed mantle cell lymphoma (MCL) incidence trends
      in the U.S. National Cancer Institute's Surveillance, Epidemiology and End
      Results (SEER) areas. Previous studies were 5 to 9 years old and MCL incidence in
      Texas remains unknown. This study updated the temporal trends and variations of
      MCL incidence in the SEER areas and compared them with counterpart data in Texas.
      Results: From 1995 to 2013, there were 2, 435 and 5, 193 newly diagnosed MCL
      patients in Texas and SEER areas. Age-adjusted MCL incidence was 0.91 per 100,000
      persons per year in Texas and 1.01 in SEER areas. MCL incidence increased
      steadily with an annual percent change (APC) of 2.56% in SEER areas and an APC of
      2.16% in Texas. In SEER areas, APCs for MCL incidence were significantly
      different from zero in patients with advanced stage tumor (3.33%), male (2.71%),
      elderly patients >= 80 years old (4.21%) and non-Hispanic white patients (2.83%)
      (all P < 0.05). Similar patterns were found in Texas for both incidence rates and
      APCs. Materials and methods: We identified all adult patients with newly
      diagnosed MCL in Texas Cancer Registry and SEER databases from 1995 to 2013. Age
      adjusted incidence rates were calculated and negative binomial regression model
      was used to assess the factors associated with MCL incidence. Conclusions: MCL
      incidence rates increased over time in both Texas and SEER areas, with increases
      being greater in male, non-Hispanic white, and elderly patient >=70 years with
      advanced stage tumors. Texas has similar MCL incidence trends and disparities as
      the national SEER areas.

PMID- 29348845
TI  - Decreased expression of the long non-coding RNA SLC7A11-AS1 predicts poor
      prognosis and promotes tumor growth in gastric cancer.
AB  - Many lncRNA and mRNA sense-antisense transcripts have been systematically
      identified in malignant cells. However, the molecular mechanisms of most lncRNA
      mRNA pairs in gastric cancer remain largely unknown. We found the gastric cancer
      associated lncRNA SLC7A11-AS1 and coding transcript mRNA SLC7A11 in human gastric
      cancer specimens by microarray. SLC7A11-AS1, antisense to SLC7A11, is
      significantly down-regulated in gastric cancer and could promote tumor growth in
      vitro and in vivo. The effects of SLC7A11-AS1 depend on the regulation of SLC7A11
      via the ASK1-p38MAPK/JNK signaling pathway. These findings suggest that decreased
      expression of SLC7A11-AS1 contributes to the progression of gastric cancer and
      may be a novel diagnostic biomarker and effective therapeutic target in gastric
      cancer patients.

PMID- 29348846
TI  - ST6GALNAC1 plays important roles in enhancing cancer stem phenotypes of
      colorectal cancer via the Akt pathway.
AB  - Colorectal cancer (CRC) is a mortal disease due to treatment resistance,
      recurrence and distant metastasis. Emerging evidence has revealed that a small
      sub-population of cancer cells termed cancer stem cells (CSCs)/ cancer-initiating
      cells (CICs) is endowed with high levels of tumor-initiating ability, self
      renewal ability and differentiation ability and is responsible for treatment
      resistance, recurrence and distant metastasis. Eradication of CSCs/CICs is
      essential to improve current treatments. However, the molecular mechanisms by
      which CSCs/CICs are maintained are still elusive. In this study, we aimed to
      determine the molecular mechanisms by which colorectal (CR)-CSCs/CICs in are
      maintained human primary CRC cells. CR-CSCs/CICs were isolated by sphere-culture
      and the ALDEFLUOR assay, and transcriptome analysis revealed that the gene ST6 N
      Acetylgalactosaminide Alpha-2,6-Sialyltransferase 1 (ST6GALNAC1) was expressed at
      high levels in CR-CSCs/CICs. Overexpression of ST6GALNAC1 enhanced the expression
      of sialyl-Tn (STn) antigen, which is carried by the CSC marker CD44, and
      increased the sphere-forming ability and resistance to a chemotherapeutic
      reagent. The opposite phenomena were observed by gene knockdown using siRNA.
      Furthermore, the Akt pathway was activated in ST6GANAC1-overexpressed cells, and
      activation of the pathway was cancelled by gene knockdown of galectin-3. The
      results indicate that ST6GALNAC1 has a role in the maintenance of CR-CSCs/CICs by
      activating the Akt pathway in cooperation with galectin-3 and that ST6GalNAC1 (or
      STn antigen) might be a reasonable molecule for CSC/CIC-targeting therapy.

PMID- 29348847
TI  - Distinct roles of TRAF6 and TAK1 in the regulation of adipocyte survival,
      thermogenesis program, and high-fat diet-induced obesity.
AB  - Chronic low-grade inflammation, adipocyte hypertrophy, and glucose intolerance
      are common features of obesity and a risk factor for cancer. Tumor necrosis
      factor (TNF) receptor-associated factor 6 (TRAF6) is an adaptor protein that also
      possesses a non-conventional E3 ubiquitin ligase activity. In response to
      receptor-mediated events, TRAF6 activates transforming growth factor-activated
      kinase 1 (TAK1), which leads to activation of the MAPK and nuclear factor-kappa B
      (NF-kappaB) signaling pathways. However, the roles of TRAF6 and TAK1 in the
      regulation of adipocyte function remain less understood. Here, we demonstrate
      that adipocyte-specific deletion of TAK1, but not TRAF6, in mice reduces the
      survival of adipocytes and abundance of white adipose tissue (WAT). Adipocyte
      specific ablation of TAK1, but not TRAF6, increases the expression for markers of
      beige/brown fat in WAT. Deletion of TAK1 in WAT increases phosphorylation of
      AMPK, abundance of PGC-1alpha, non-canonical NF-kappaB signaling, markers of M2
      macrophages, and diminishes phosphorylation of JNK and canonical NF-kappaB
      signaling. Levels of TRAF6 and enzymatic activity of TAK1 are increased in WAT of
      mice fed with high-fat diet (HFD). Our results demonstrate that ablation of TAK1
      drastically reduces HFD-induced obesity and improves energy expenditure and
      glucose metabolism. In contrast, adipocyte-specific ablation of TRAF6 has a
      minimal effect on HFD-induced obesity. Collectively, our results suggest that
      even though TRAF6 is an upstream activator of TAK1 in many signaling cascades,
      inactivation of TAK1, but not TRAF6, regulates adipocyte survival, energy
      expenditure, and HFD-induced obesity in mice.

PMID- 29348848
TI  - PD-L1 expression in tumor tissue and peripheral blood of patients with oral
      squamous cell carcinoma.
AB  - Background: Immune checkpoints like programmed cell death-1 (PD-1) and its ligand
      PD-L1 are involved in immune escape mechanisms of solid tumors including oral
      squamous cell carcinoma (OSCC). Inhibitors of the pathway are successfully used
      for treating especially advanced disease. However, the physiological relevance of
      PD-1/PD-L1-signaling in OSCC is insufficiently understood. The aim of the study
      was to analyze if PD-L1 expression in tumor tissue and peripheral blood samples
      of OSCC patients is associated with histomorphological tumor parameters and if PD
      L1 expression in patients is different from controls. Results: OSCC tumor
      specimens showed a significantly higher PD-L1 expression than oral mucosa
      controls (p < 0.001; upregulation more than 3-fold). Cross-tabulation revealed an
      association of increased expression of PD-L1 mRNA in tissue specimens with
      malignancy (p < 0.001).OSCC cases with higher tumor grade and cases with lymph
      node metastases (N+) were significantly (p < 0.05) associated with increased PD
      L1 expression in peripheral blood. Cross-tabulation revealed an significant
      association with lymph node metastases (N+) (p <= 0.002). Materials and Methods:
      PD-L1 mRNA expression was analyzed in tumor specimens and corresponding samples
      of healthy oral mucosa and peripheral blood of 45 OSCC patients and 36 healthy
      control persons using RT-qPCR analysis. A Mann-Whitney U-test, a cut-off point
      analysis and a Chi-square test were carried out. Conclusions: PD-L1 expression in
      OSCC could contribute to the immunosuppressive local tumor microenvironment.
      Increased malignant behavior (higher tumor grade, positive nodal status) might be
      associated with PD-L1 mediated systemic immune tolerance. Thus, PD-L1 expression
      in peripheral blood might be an indicator of the existence of metastatic disease
      (N+) in OSCC.

PMID- 29348849
TI  - Reduced levels of N'-methyl-2-pyridone-5-carboxamide and lysophosphatidylcholine
      16:0 in the serum of patients with intrahepatic cholangiocarcinoma, and the
      correlation with recurrence-free survival.
AB  - We searched for metabolic biomarkers that may predict the prognosis of patients
      with intrahepatic cholangiocarcinoma (IHCC). To this end, a total of 237 serum
      samples were obtained from IHCC patients (n = 87) and healthy controls (n = 150),
      and serum metabolites were analyzed by liquid chromatography-tandem mass
      spectrometry (LC-MS/MS). Two stratified algorithms were used to select the
      metabolites, the levels of which predicted the prognosis of IHCC patients. We
      performed MS/MS and multiple-reaction-monitoring MS analyses to identify and
      quantify the selected metabolites. Continuous biomarker levels were dichotomized
      based on cutoffs that maximized between-group differences in recurrence-free
      survival (RFS) in terms of the log-rank test statistic. These RFS differences
      were analyzed using the log-rank test, and survival curves were drawn with the
      aid of the Kaplan-Meier method. Six metabolites (l-glutamine,
      lysophosphatidylcholine [LPC] 16:0, LPC 18:0, N'-methyl-2-pyridone-5-carboxamide
      [2PY], fibrinopeptide A [FPA] and uric acid) were identified as candidate
      metabolic biomarkers for predicting the prognosis of IHCC patients. Of these
      metabolites, levels of l-glutamine, uric acid, LPC 16:0, and LPC 18:0 were
      significantly lower in the serum from IHCC patients, whereas levels of 2PY and
      FPA were significantly higher (p < 0.01). 2PY and LPC 16:0 showed significantly
      better RFS at low level than high level (2PY, median RFS: 15.16 months vs. 5.90
      months, p = 0.037; LPC 16:0, median RFS: 15.62 months vs. 9.83 months, p =
      0.035). The findings of this study suggest that 2PY and LPC 16:0 identified by
      metabolome-based approaches may be useful biomarkers for IHCC patients.

PMID- 29348850
TI  - Novel indazole-based small compounds enhance TRAIL-induced apoptosis by
      inhibiting the MKK7-TIPRL interaction in hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is one of the most malignant tumors. Although
      various treatments, such as surgery and chemotherapy, have been developed, a
      novel alternative therapeutic approach for HCC therapy is urgently needed. Tumor
      necrosis factor-related apoptosis inducing ligand (TRAIL) is a promising anti
      cancer agent, but many cancer cells are resistant to TRAIL-induced apoptosis. To
      help overcome TRAIL resistance in HCC cancer cells, we have identified novel
      chemical compounds that act as TRAIL sensitizers. We first identified the hit
      compound, TRT-0002, from a chemical library of 6,000 compounds using a previously
      developed high-throughput enzyme-linked immunosorbent assay (ELISA) screening
      system, which was based on the interaction of mitogen-activated protein kinase
      kinase 7 (MKK7) and TOR signaling pathway regulator-like (TIPRL) proteins and a
      cell viability assay. To increase the efficacy of this TRAIL sensitizer, we
      synthesized 280 analogs of TRT-0002 and finally identified two lead compounds
      (TRT-0029 and TRT-0173). Co-treating cultured Huh7 cells with either TRT-0029 or
      TRT-0173 and TRAIL resulted in TRAIL-induced apoptosis due to the inhibition of
      the MKK7-TIPRL interaction and subsequent phosphorylation of MKK7 and c-Jun N
      terminal kinase (JNK). In vivo, injection of these compounds and TRAIL into HCC
      xenograft tumors resulted in tumor regression. Taken together, our results
      suggest that the identified lead compounds serve as TRAIL sensitizers and
      represent a novel strategy to overcome TRAIL resistance in HCC.

PMID- 29348851
TI  - Comprehensive analysis of mRNA-lncRNA co-expression profile revealing crucial
      role of imprinted gene cluster DLK1-MEG3 in chordoma.
AB  - Chordoma is a rare bone tumor with high recurrence rate, but the mechanism of its
      development is unclear. Long non-coding RNAs(lncRNAs) are recently revealed to be
      regulators in a variety of biological processed by targeting on mRNA
      transcription. Their expression profile and function in chordoma have not been
      investigated yet. In this study, we firstly performed the comprehensive analysis
      of the lncRNA and coding genes expression analysis with three chordoma samples
      and three fetal nucleus pulposus tissues. lncRNA and gene microarrays were used
      to determine the differentially expressed lncRNAs and protein coding genes. 2786
      lncRNAs and 3286 coding genes were significantly up-regulated in chordoma, while
      2042 lncRNAs and 1006 coding genes were down-regulated. Pearson correlation
      analysis was conducted to correlate differentially expressed lncRNAs with protein
      coding genes, indicating a comprehensive lncRNA-coding gene co-expression network
      in chordoma. Cis-correlation analysis showed that various transcripts of MEG3 and
      MEG8 were paired with the most differentially expressed gene DLK1. As located in
      the same locus, we further analyzed the miRNA clusters in this region, and
      identified that 61.22% of these miRNAs were significantly down-regulated,
      implying the silence of the imprinted gene cluster DLK1-MEG3. Overexpression of
      MEG3 suppressed the proliferation of chordoma cells. Our study pointed out the
      potential role of lncRNAs in chordoma, presented the lncRNA-coding genes co
      expression profile, and revealed that imprinted gene cluster DLK1-MEG3
      contributes to the pathogenesis of chordoma development.

PMID- 29348852
TI  - Reduced FBXW7 expression in pancreatic cancer correlates with poor prognosis and
      chemotherapeutic resistance via accumulation of MCL1.
AB  - Pancreatic cancer is a highly malignant tumor type with poor outcomes, and
      elucidation of the mechanisms involved in cancer progression and therapeutic
      resistance is critical. FBXW7 is a key regulator of tumor malignant potential,
      and its substrate MCL1 regulates therapeutic resistance in human malignancies.
      Therefore, determination of the relevance of FBXW7 expression is critical for
      improving patient outcomes. In this study, we investigated the function and
      clinical significance of FBXW7 in pancreatic cancer. FBXW7 expression was
      evaluated by immunohistochemistry in 122 pancreatic cancer tissues. Reduced FBXW7
      expression was significantly associated with advanced venous invasion, high MCL1
      expression, enhanced Ki-67 expression, and poor prognosis and was an independent
      poor prognostic factor. Among patients who underwent gemcitabine treatment after
      surgery, reduced FBXW7 expression was also significantly associated with poor
      prognosis. Knockdown of FBXW7 in vitro enhanced cell proliferation, and
      migration, and invasion abilities and promoted gemcitabine and nab-paclitaxel
      chemoresistance in pancreatic cancer cells. Moreover, FBXW7-knockdown cells
      showed accumulation of MCL1, and the enhanced chemoresistance observed in FBXW7
      knockdown cells was eliminated by MCL1 suppression. These results suggested that
      FBXW7 was associated with cancer progression and mediated sensitivity to
      gemcitabine and nab-paclitaxel via MCL1 accumulation in pancreatic cancer. Thus,
      the FBXW7/MCL1 axis may be a promising therapeutic tool to overcome refractory
      pancreatic cancer.

PMID- 29348853
TI  - 3D-cultivation of NSCLC cell lines induce gene expression alterations of key
      cancer-associated pathways and mimic in-vivo conditions.
AB  - This work evaluated gene expression differences between a hanging-drop 3D NSCLC
      model and 2D cell cultures and their in-vivo relevance by comparison to patient
      derived data from The Cancer Genome Atlas. Gene expression of 2D and 3D cultures
      for Colo699 and A549 were assessed using Affymetrix HuGene 1.0 ST gene chips.
      Biostatistical analyses tested for reproducibility, comparability and significant
      differences in gene expression profiles between cell lines, experiments and
      culture methods. The analyses revealed a high interassay correlation within
      specific culture systems proving a high validity. 979 genes were altered in A549
      and 1106 in Colo699 cells due to 3D cultivation. The overlap of changed genes
      between the cell lines was small (149), but the involved pathways in the reactome
      and GO- analyses showed a high overlap with DNA methylation, cell cycle, SIRT1,
      PKN1 pathway, DNA repair and oxidative stress as well known cancer-associated
      representatives. Additional specific GSEA-analyses revealed changes in
      immunologic and endothelial cell proliferation pathways, whereas hypoxic, EMT and
      angiogenic pathways were downregulated. Gene enrichment analyses showed 3D
      induced gene up-regulations in the cell lines 38 to be represented in in-vivo
      samples of NSCLC patients using data of The Cancer Genome Atlas. Thus, our 3D
      NSCLC model might provide a tool for early drug development and investigation of
      microenvironment-associated mechanisms. However, this work also highlights the
      need for further individualization and model adaption to address remaining
      challenges.

PMID- 29348854
TI  - Acid ceramidase and its inhibitors: a de novo drug target and a new class of
      drugs for killing glioblastoma cancer stem cells with high efficiency.
AB  - Glioblastoma remains the most common, malignant primary cancer of the central
      nervous system with a low life expectancy and an overall survival of less than
      1.5 years. The treatment options are limited and there is no cure. Moreover,
      almost all patients develop recurrent tumors, which typically are more
      aggressive. Therapeutically resistant glioblastoma or glioblastoma stem-like
      cells (GSCs) are hypothesized to cause this inevitable recurrence. Identifying
      prognostic biomarkers of glioblastoma will potentially advance knowledge about
      glioblastoma tumorigenesis and enable discovery of more effective therapies.
      Proteomic analysis of more than 600 glioblastoma-specific proteins revealed, for
      the first time, that expression of acid ceramidase (ASAH1) is associated with
      poor glioblastoma survival. CD133+ GSCs express significantly higher ASAH1
      compared to CD133- GSCs and serum-cultured glioblastoma cell lines, such as
      U87MG. These findings implicate ASAH1 as a plausible independent prognostic
      marker, providing a target for a therapy tailored toward GSCs. We further
      demonstrate that ASAH1 inhibition increases cellular ceramide level and induces
      apoptosis. Strikingly, U87MG cells, and three different patient-derived
      glioblastoma stem-like cancer cell lines were efficiently killed, through
      apoptosis, by three different known ASAH1 inhibitors with IC50's ranging from 11
      104 MUM. In comparison, the standard glioblastoma chemotherapy agent,
      temozolomide, had minimal GSC-targeted effects at comparable or even higher
      concentrations (IC50 > 750 MUM against GSCs). ASAH1 is identified as a de novo
      glioblastoma drug target, and ASAH1 inhibitors, such as carmofur, are shown to be
      highly effective and to specifically target glioblastoma GSCs. Carmofur is an
      ASAH1 inhibitor that crosses the blood-brain barrier, a major bottleneck in
      glioblastoma treatment. It has been approved in Japan since 1981 for colorectal
      cancer therapy. Therefore, it is poised for repurposing and translation to
      glioblastoma clinical trials.

PMID- 29348855
TI  - Associations between erythropoietin polymorphisms and risk of diabetic
      microvascular complications.
AB  - We conducted a meta-analysis to evaluate the relationship between erythropoietin
      (EPO) polymorphisms and diabetic microvascular complications. We searched the
      PubMed, Embase, Cochrane library, Web of Science, Wanfang, and Chinese National
      Knowledge Infrastructure databases for appropriate studies. Odds ratios (ORs)
      with 95% confidence intervals (CIs) were calculated to evaluate the associations.
      Ultimately, eight studies consisting of 2,861 cases and 2,136 controls were
      identified and included in our meta-analysis. Results with our genotype model
      indicated an association between rs1617640 polymorphisms and diabetic
      microvascular complications (TT vs. GG: OR = 1.544, 95% CI = 1.089-2.189, P =
      0.015). No clear associations between the rs1617640 and rs507392 polymorphisms
      and diabetic retinopathy were observed. By contrast, rs551238 polymorphisms were
      associated with increased diabetic retinopathy risk (allele model: OR = 0.774,
      95% CI = 0.658-0.911, P = 0.002; genotype model: AC vs. CC: OR = 0.598, 95% CI =
      0.402-0.890, P = 0.011; dominant model: OR = 0.561, 95% CI = 0.385-0.817, P =
      0.003; recessive model: OR = 0.791, 95% CI = 0.643-0.973, P = 0.026). These
      results indicate that EPO polymorphisms are a risk factor for diabetic
      microvascular complications.

PMID- 29348856
TI  - Prognostic value of diametrically polarized tumor-associated macrophages in
      multiple myeloma.
AB  - Tumor-associated macrophages (TAMs) are correlated with the prognosis of
      different types of solid tumors and lymphoma, according to many clinical studies.
      In vitro experiments have demonstrated the roles of these cells in myeloma cell
      survival, angiogenesis, immunomodulation, drug resistance, and the interaction
      between malignant myeloma cells and the microenvironment. Here, we investigated
      the prognostic significance of TAMs in patients with multiple myeloma (MM). We
      evaluated the polarized functional status of bone marrow infiltrated by TAMs by
      immunohistochemical staining of CD68, iNOS, and CD163 in 240 patients with MM
      from January 2009 to December 2014. The overall response rates to chemotherapy
      were lower in patients with high CD68+ or CD163+ TAM densities than in those with
      low densities. Kaplan-Meier analysis showed that the progression-free survival
      (PFS, p = 0.001) and overall survival (OS, p < 0.001) of patients with low CD163+
      TAM density were significantly higher than those of patients with high CD163+ TAM
      density. Furthermore, combined analysis of iNOS+ and CD163+ TAMs (iNOS/CD163
      signature) exhibited greater power in predicting patient outcomes for both PFS (p
      < 0.001) and OS (p < 0.001). Moreover, Cox regression analysis identified iNOS+
      and CD163+ TAMs as independent prognostic factors (p = 0.007, p < 0.001,
      respectively). These factors could be combined with the international staging
      system (ISS) to generate a predictive nomogram for patient outcomes. Our findings
      suggest that the mosaic of diametrically polarized TAMs is a novel independent
      prognostic factor that could be integrated into the evaluation of and therapy for
      MM.

PMID- 29348858
TI  - The survival benefit of neoadjuvant chemotherapy and pCR among patients with
      advanced stage triple negative breast cancer.
AB  - Triple negative breast cancer (TNBC) is an aggressive subtype that accounts for
      15-20% of cases, with a higher incidence of relapse/death. Even with adjuvant
      chemotherapy, the 5 year distant metastasis-free survival rate remains low. A
      total of 452 tumor registry patients with TNBC and no evidence of metastatic
      disease were identified over the period of 1996-2011. The median age and follow
      up time were 51 (range=21-88) and 3.9 (range=0.14-14) years. Approximately 75% of
      patients with stage III disease received neoadjuvant chemotherapy (NACT) compared
      with 47% for stage II. Patients with stage I disease predominantly received
      adjuvant chemotherapy (ACT). Among those who underwent NACT (n=202), 33% had a
      pathological complete response (pCR). Overall (OS) and disease-free (DFS)
      survival were significantly longer among patients achieving pCR (versus residual
      disease) following NACT (OS: all patients P<0.0001, stage II P<0.0001, stage III
      P=0.0062; DFS: all patients P<0.0001, stage II P=0.0011, stage III P=0.015). ACT
      was not associated with improved OS or DFS for stage III disease. Adjustment for
      age, chemotherapy, health insurance type, lymphovascular invasion, race,
      radiation, and surgery did not alter our results. These findings suggest that pCR
      following NACT is associated with improved survival among patients with TNBC,
      independent of diagnostic stage.

PMID- 29348859
TI  - The effect of systematic lower-limb rehabilitation training in elderly patients
      undergoing lumbar fusion surgery: a retrospective study.
AB  - Objectives: The purpose of this study was to explore the effect of systematic
      lower-limb rehabilitation training in elderly patients undergoing lumbar fusion
      surgery due to serious degenerative intervertebral disc diseases. Results: At the
      1st week after surgery, clinical rehabilitation effect in intervention group was
      better regarding lower-limb muscle strength, lower-limb DVT, VAS score, and ODI,
      as compared with control group (all p < 0.05). During the first two weeks after
      surgery, satisfaction rate in intervention group was higher than that in control
      group. However, there was no significant difference at last follow-up after
      surgery when comparing intervention group to control group. Materials and
      Methods: We retrospectively collected medical records of elderly patients (aged
      >= 60 yrs) undergoing lumbar fusion surgery between 01/2013 and 01/2015 in our
      department. Some of the identified patients randomly underwent postoperative
      systematic training of lower-limb rehabilitation gymnastics (intervention group,
      n = 240), the others not (control group, n = 300). During postoperative period,
      intervention group received lower-limb rehabilitation gymnastics treatment for 3
      months, but control group did not. All patients were routinely asked to return
      hospital for a check in the 1st postoperative week, as well as the 2nd week, the
      1st month, and the 3rd month. Clinical outcomes were evaluated by scoring lower
      limb muscle strength, detecting lower-limb deep venous thrombosis (DVT), visual
      analogue scale (VAS) score, lumbar JOA score, Oswestry disability index (ODI)
      questionnaire, and performing satisfaction survey. Conclusions: In early
      postoperative stage, systematic lower-limb rehabilitation training can
      effectively speed up the recovery, beneficial to reducing lower-limb DVT and
      increasing patient satisfaction rate.

PMID- 29348857
TI  - Influenza vaccination might reduce the risk of ischemic stroke in patients with
      atrial fibrillation: A population-based cohort study.
AB  - Purpose: Atrial fibrillation (AF) is associated with the risk of ischemic stroke,
      regardless of the administration of appropriate antithrombotic prophylaxis. This
      study investigated whether influenza vaccination is associated with the risk of
      ischemic stroke, to determine a solution to reduce this risk in patients with AF.
      Methods: We used data from the Taiwan National Health Insurance Research
      Database. The study cohort comprised all patients diagnosed as having AF (n = 14
      454) before January 1, 2005; these patients were followed until December 31,
      2012. The index date was January 1, 2005. A propensity score was derived using a
      logistic regression model to estimate the effect of vaccination by accounting for
      covariates that predict receiving the intervention (vaccine). A Cox proportional
      hazard model was used to calculate the hazard ratios (HRs) of ischemic stroke in
      vaccinated and unvaccinated patients with AF. Results: We included 6570 patients
      (2547 [38.77%] with and 4023 [61.23%] without influenza vaccination). The
      adjusted HRs (aHRs) of ischemic stroke were lower in the vaccinated patients than
      in the unvaccinated patients (influenza season, noninfluenza season, and all
      seasons: aHRs = 0.59, 0.50, and 0.55; P < 0.001, P < 0.001, and P < 0.001,
      respectively). Conclusions: Influenza vaccination might exert a dose-response
      effect against ischemic stroke in patients with AF who have risk factors for
      ischemic stroke by reducing the incidence of ischemic stroke, particularly in
      those aged 65-74 and >=75 y.

PMID- 29348860
TI  - Silencing ROR1 and ROR2 inhibits invasion and adhesion in an organotypic model of
      ovarian cancer metastasis.
AB  - OBJECTIVE: Elevated expression of the ROR1 and ROR2 Wnt receptors has been noted
      in both the tumour and stromal compartments of ovarian cancer patient tissue
      samples. In vitro studies have suggested these receptors play a role in ovarian
      cancer metastasis. However, these previous studies have utilised simple 2D in
      vitro models to investigate cancer cell growth and migration, which does not
      allow investigation of stromal involvement in Wnt driven metastasis. AIM: To
      investigate targeting ROR1 and ROR2 using a primary co-culture 3D model of
      epithelial ovarian cancer dissemination to the omentum. METHODS: Primary
      fibroblasts (NOF) and mesothelial (HPMC) cells were isolated from fresh samples
      of omentum collected from women with benign or non-metastatic conditions and
      cultured with collagen to produce a organotypic 3D model. Stable shRNA knockdown
      of ROR1, ROR2 and double ROR1/ROR2 in OVCAR4 cells were plated onto the 3D model
      to measure adhesion, or using a transwell to measure invasion. Gene expression
      changes in primary cells upon OVCAR4 interaction was evaluated using indirect
      transwell co-culture. RESULTS: Double knockdown of ROR1 and ROR2 strongly
      inhibited cell adhesion (p<0.05) and invasion (P<0.05) to the omentum model. ROR2
      was up regulated in primary fibroblasts when cultured with OVCAR4 (P=0.05) and
      ectopic overexpression of ROR2 in NOFs inhibited cell proliferation (P<0.01) but
      increased cell migration. CONCLUSION: The combination of ROR1 and ROR2 signalling
      influences ovarian cancer dissemination to the omentum, however ROR2 may also
      play a role in stromal activation during metastasis. Therefore, targeting both
      ROR1 and ROR2 may be a powerful approach to treating ovarian cancer.

PMID- 29348861
TI  - Primary tumor-associated expression of CXCR4 predicts formation of local and
      systemic recurrency in head and neck squamous cell carcinoma.
AB  - Objectives: Despite modern treatment regimens, overall survival in head and neck
      squamous cell carcinomas (HNSCC) is less than 50% due to local and systemic
      disease recurrency. The current study aims to identify molecular markers in
      primary tumor specimens that predict the risk for local and systemic recurrency
      at the time of initial diagnosis. Methods: The study included clinic-pathological
      data of 1,057 HNSCC. MMP2/9, TIMP1/2, CXCR4, and CXCL12 immunohistochemistry was
      done in 150 randomly selected specimens. For statistics, we employed Chi square,
      Fisher exact, and Student's t-test. Overall survival (OS) was calculated by
      Kaplan-Meier and log-rank test. Prognostic variables were subsequently evaluated
      by Cox regression for forward selection. Results: CXCR4 positive specimens
      demonstrated a significant increased risk for tumor recurrency associated death
      (rT: HR 10.07; p=0.001 / rN: HR 5.04; p=0.013 / rM: HR 2.49; p=0.029) when
      compared with their unaltered counterparts. Expression of MMP9, TIMP2, CXCR4, and
      CXCL12 was significantly increased in distant metastasized patients (p<0.0001)
      and showed significant cross-correlation. In addition, CXCR4 positivity was
      associated with an increased risk to die due to enhanced T or N status (T1/2 vs.
      T3/4: HR 5.78; p=0.017; N0 vs. N+: HR 5.18; p=0.033). Conclusion: CXCR4
      positivity in tumor samples at initial diagnosis were associated with reduced
      overall survival, in particular with respect to increasing T/N status, local and
      systemic recurrency.

PMID- 29348862
TI  - Digital gene expression analysis in mice lung with coinfection of influenza and
      streptococcus pneumoniae.
AB  - Influenza A virus (IAV) and Streptococcus pneumoniae (SP) are two major upper
      respiratory tract pathogens that can also cause infection in polarized bronchial
      epithelial cells to exacerbate disease in coinfected individuals which may result
      in significant morbidity. However, the underlying molecular mechanism is poorly
      understood. Here, we employed BALB/c ByJ mice inflected with SP, IAV, IAV
      followed by SP (IAV+SP) and PBS (Control) as models to survey the global gene
      expression using digital gene expression (DGE) profiling. We attempt to gain
      insights into the underlying genetic basis of this synergy at the expression
      level. Gene expression profiles were obtain using the Illimina/Hisseq sequencing
      technique, and further analyzed by enrichment analysis of Gene Ontology (GO) and
      Pathway function. The hematoxylin-eosin (HE) staining revealed different tissue
      changes in groups during which IAV+SP group showed the most severe cell
      apoptosis. Compared with Control, a total of 2731, 3221 and 3946 differentially
      expressed genes (DEGs) were detected in SP, IAV and IAV+SP respectively. Besides,
      sixty-two GO terms were identified by Gene Ontology functional enrichment
      analysis, such as cell killing, biological regulation, response to stimulus,
      signaling, biological adhesion, enzyme regulator activity, receptor regulator
      activity and translation regulator activity. Pathway significant enrichment
      analysis indicated the dysregulation of multiple pathways, including apoptosis
      pathway. Among these, five selected genes were further verified by quantitative
      reverse transcription-polymerase chain reaction (qRT-PCR). This study shows that
      infection with SP, IAV or IAV+SP induces apoptosis with different degrees which
      might provide insights into the molecular mechanisms to facilitate further
      research.

PMID- 29348863
TI  - No association between TP53 Arg72Pro polymorphism and ovarian cancer risk:
      evidence from 10113 subjects.
AB  - The TP53 gene product is an important regulator of cell growth and a tumor
      suppressor. The association between TP53 Arg72Pro polymorphism and ovarian cancer
      risk has been widely investigated, but the results are contradictory. We
      therefore searched the PubMed, EMBASE and Chinese Biomedical databases for
      studies on the relation between TP53 Arg72Pro polymorphism and ovarian cancer
      risk. Our final meta-analysis included 24 published studies with 3271 cases and
      6842 controls. Pooled results indicated that there was no significant association
      between TP53 Arg72Pro polymorphism and ovarian cancer risk [Pro/Pro vs. Arg/Arg:
      odds ratio (OR) =1.04, 95% confidence interval (CI) = 0.81-1.34; Arg/Pro vs.
      Arg/Arg: OR = 1.14, 95% CI = 0.96-1.36; recessive: OR = 1.05, 95% CI = 0.90-1.22;
      dominant: OR = 1.12, 95% CI = 0.94-1.33; and Pro vs. Arg: OR = 1.06, 95% CI=0.93
      1.20]. Likewise, stratified analyses failed to reveal a genetic association.
      Despite some limitations, the present meta-analysis provides statistical evidence
      indicating a lack of association between TP53 Arg72Pro polymorphism and ovarian
      cancer risk.

PMID- 29348864
TI  - The macro-evolutionary events in esophageal squamous cell carcinoma.
AB  - Understanding the evolutionary processes operative in cancer genome may provide
      insights into clinical outcome and drug-resistance. However, studies focus on
      genomic signatures, especially for macro-evolutionary events, in esophageal
      squamous cell carcinoma (ESCC) are limited. Here, we integrated published genomic
      sequencing data to investigate underlying evolutionary characteristics in ESCC.
      We found most of ESCC genomes were polyploidy with high genomic instability.
      Whole genome doubling that acts as one of mechanisms for polyploidy was predicted
      as a late event in the majority of ESCC genome. Moreover, loss of heterozygosity
      events were more likely to occur in chromosomes harboring tumor suppressor genes
      in ESCC. The 40% of neutral loss of heterozygosity events was not a result of
      genome doubling, suggesting an alternative mechanism for neutral loss of
      heterozygosity formation. Importantly, deconstruction of copy number alterations
      extending to telomere revealed that telomere-bounded copy number alterations play
      a critical role for amplification/deletion of oncogenes/suppressor genes. For
      well-known genes SOX2, PIK3CA and TERT, nearly all of their amplifications were
      telomere bounded, which was further confirmed in a Japanese ESCC cohort.
      Furthermore, we provide evidence that karyotype evolution was mostly punctuated
      in ESCC. Collectively, our data reveal the potential biological role of whole
      genome doubling, neutral loss of heterozygosity and telomere-bounded copy number
      alterations, and highlight mecro-evolution in ESCC tumorigenesis.

PMID- 29348865
TI  - Targeting T-cell malignancies using anti-CD4 CAR NK-92 cells.
AB  - Peripheral T-cell lymphomas (PTCLs) are a group of very aggressive non-Hodgkin's
      lymphomas (NHLs) with poor prognoses and account for a majority of T-cell
      malignancies. Overall, the standard of care for patients with T-cell malignancies
      is poorly established, and there is an urgent clinical need for a new approach.
      As demonstrated in B-cell malignancies, chimeric antigen receptor (CAR)
      immunotherapy provides great hope as a curative treatment regimen. Because PTCLs
      develop from mature T-cells, these NHLs are commonly CD4+, and CD4 is highly and
      uniformly expressed. Therefore, CD4 is an ideal target for PTCL CAR
      immunotherapy. To that effect, we created a robust third-generation anti-CD4 CAR
      construct (CD4CAR) and introduced it into clonal NK cells (NK-92). CD4CAR NK-92
      cells specifically and robustly eliminated diverse CD4+ human T-cell leukemia and
      lymphoma cell lines (KARPAS-299, CCRF-CEM, and HL60) and patient samples ex vivo.
      Furthermore, CD4CAR NK-92 cells effectively targeted KARPAS-299 cells in vivo
      that modeled difficult-to-access lymphoma nodules, significantly prolonging
      survival. In our study, we present novel targeting of CD4 using CAR-modified NK
      cells, and demonstrate efficacy. Combined, our data support CD4CAR NK cell
      immunotherapy as a potential new avenue for the treatment of PTCLs and CD4+ T
      cell malignancies.

PMID- 29348866
TI  - Protein methyltransferases and demethylases dictate CD8+ T-cell exclusion in
      squamous cell carcinoma of the head and neck.
AB  - A subset of patients with recurrent/metastatic squamous cell carcinoma of the
      head and neck (SCCHN) benefit from pembrolizumab and nivolumab, but the majority
      of patients do not probably due to lack of activated cytotoxic CD8+ T-cells in
      their tumor tissues. Herein, we aim to investigate whether specific protein
      methyltransferases (PMTs) and demethylases (PDMTs) could play any roles in the
      CD8+ T-cell exclusion process in HPV-negative SCCHN. RNA sequencing data from the
      TCGA database were interrogated for HPV-negative SCCHN patients using a 10-gene
      chemokine signature that classifies SCCHN tissues into CD8+ T-cell inflamed and
      non-CD8+ T-cell inflamed phenotypes. Among 53 PMT/PDMT genes examined in the TCGA
      HPV-negative SCCHN database, expression levels of 15 PMT/PDMT genes were
      significantly negatively correlated with the chemokine signature score and CD8
      mRNA expression levels. The expression level of each of these 15 PMT/PDMT genes
      showed significantly negative correlations with immune-active chemokines, as well
      as HLA class I and APM molecules. siRNA-mediated knockdown of a candidate PMT,
      SMYD3, led to upregulation of CXCL9, CXCL10, CXCL11 and TAP1 at mRNA and protein
      levels in HPV-negative SCCHN cell lines. These findings demonstrate that
      overexpression of some PMTs and PDMTs seems to be related with the non-CD8+ T
      cell inflamed phenotype and may drive CD8+ T-cell exclusion in HPV-negative
      SCCHN. This study suggests that chromatin modifiers contribute to CD8+ T-cell
      exclusion and antigen presentation capacity of HPV-negative SCCHN, supporting
      that targeting of specific PMTs and/or PDMTs could enhance CD8+ T-cell
      infiltration and increase the proportion of patients that may benefit from
      immunotherapy.

PMID- 29348867
TI  - Pleural MAC30 as a prognostic marker in NSCLC with malignant pleural effusion.
AB  - Over-expressed meningioma-associate protein (MAC30) in tissues was associated
      with malignant tumor differentiation, metastasis and poor prognosis. However, the
      attention of MAC30 in pleural effusion from lung tumor is insufficient. Our
      retrospective study was prepared to explore the clinical values on diagnosis and
      prognosis of MAC30 from malignant pleural effusion (MPE) in non-small cell lung
      cancer (NSCLC). Levels of MAC30 were confirmed in MPE from 48 NSCLC patients and
      in benign pleural effusion (BPE) from 45 controls via enzyme-linked immunosorbent
      assay (ELISA). The association of MAC30 in MPE with clinical significance was
      further determined. We found that the levels of MAC30 in MPE were obviously
      higher than those in BPE (p < 0.05). Moreover, with a cutoff point (17.5 ng/ml),
      we confirmed the sensitivity and specificity of MAC30 for MPE were 82.7% and
      85.3% using ROC curve analysis. Indeed, longer overall survival (OS) was present
      in NSCLC patients with low MAC30 expression in MPE. Multivariate analysis
      explicated that elevated MAC30 in MPE was an independent prognostic factor for
      shorter OS of NSCLC. Our data suggests that MAC30 in pleural effusion could be a
      potential prognostic marker in NSCLC with MPE.

PMID- 29348868
TI  - Luminal-like HER2-negative stage IA breast cancer: a multicenter retrospective
      study on long-term outcome with propensity score analysis.
AB  - The benefit of adding chemotherapy (CT) to adjuvant hormone therapy (HT) in stage
      IA luminal-like HER2-negative breast cancer (BC) is unclear. We retrospectively
      evaluated predictive factors and clinical outcome of 1,222 patients from 4
      oncologic centers. Three hundred and eighty patients received CT and HT (CT
      cohort) and 842 received HT alone (HT-cohort). Disease-free survival (DFS) and
      overall survival (OS) were evaluated with univariate and multivariate analyses.
      We also applied the propensity score methodology. Compared with the HT-cohort,
      patients in the CT-cohort were more likely to be younger, have larger tumors of a
      higher histological grade that were Ki67-positive, and lower estrogen and
      progesterone receptor expression. At univariate analysis, a higher histological
      grade and Ki67 were significantly associated to a lower DFS. At multivariable
      analysis, only histological grade was predictive of DFS. The CT-cohort had a
      worse outcome than the HT-cohort in terms of DFS and OS, but differences
      disappeared when matched according to propensity score. In summary, patients with
      stage IA luminal-like BC had an excellent prognosis, however relapse and
      mortality were higher in the CT-cohort than in the HT-cohort. Longer use of
      adjuvant HT or other therapeutic strategies may be needed to improve outcome.

PMID- 29348869
TI  - Role of the N-terminal lid in regulating the interaction of phosphorylated MDMX
      with p53.
AB  - Murine double minute 4 protein (MDMX) is crucial for the regulation of the tumor
      suppressor protein p53. Phosphorylation of the N-terminal domain of MDMX is
      thought to affect its binding with the transactivation domain of p53, thus
      playing a role in p53 regulation. In this study, the effects of MDMX
      phosphorylation on the binding of p53 were investigated using molecular dynamics
      simulations. It is shown that in addition to the previously proposed mechanism in
      which phosphorylated Y99 of MDMX inhibits p53 binding through steric clash with
      P27 of p53, the N-terminal lid of MDMX also appears to play an important role in
      regulating the phosphorylation-dependent interactions between MDMX and p53. In
      the proposed mechanism, phosphorylated Y99 aids in pulling the lid into the p53
      binding pocket, thus inhibiting the binding between MDMX and p53. Rebinding of
      p53 appears to be facilitated by the subsequent phosphorylation of Y55, which
      draws the lid away from the binding pocket by electrostatic attraction of the
      lid's positively charged N-terminus. The ability to target these mechanisms for
      the proper regulation of p53 could have important implications for understanding
      cancer biology and for drug development.

PMID- 29348870
TI  - Nepsilon-carboxymethyl-lysine promotes calcium deposition in VSMCs via
      intracellular oxidative stress-induced PDK4 activation and alters glucose
      metabolism.
AB  - Diabetes and vascular calcification are intrinsically linked. We previously
      reported that advanced glycation end products (AGEs) accelerate calcium
      deposition in vascular smooth muscle cells (VSMCs) via excessive oxidative
      stress. However, the underlying mechanism remains poorly understood. Pyruvate
      dehydrogenase kinase 4 (PDK4) is an important mitochondrial matrix enzyme in
      cellular energy metabolism. Since hyperactivation of PDK4 has been reported in
      calcified vessels and in patients with diabetes mellitus, inhibition of PDK4
      expression may be a strategy for the prevention of diabetic vascular
      calcification. In this study, we used a rat VSMC model to investigate the role of
      PDK4 in diabetic vascular calcification and further explore the underlying
      mechanisms. We observed that Nepsilon-carboxymethyl-lysine (CML), which is a
      major immunogen of AGEs, accelerated calcium deposition in VSMCs through PDK4
      activation. An elevated level of reactive oxygen species (ROS) acted as a signal
      transduction intermediate to increase PDK4 expression. Either inhibition of PDK4
      expression or RAGE (receptor for AGEs) blockade attenuated CML-induced VSMC
      calcification, as shown by decreased alkaline phosphatase (ALP) activity and runt
      related transcription factor 2 (RUNX2) expression. Glucose consumption and
      lactate production were increased during CML-induced VSMC calcification.
      Importantly, CML accelerates glycolysis in VSMCs via a PDK4-dependent pathway. In
      conclusion, this study demonstrates a novel mechanism by which CML promotes VSMC
      calcification via PDK4 activation and alters glucose metabolism in VSMCs.

PMID- 29348871
TI  - Radiation therapy for stage IVA uterine cervical cancer: treatment outcomes
      including prognostic factors and risk of vesicovaginal and rectovaginal fistulas.
AB  - Purpose: To evaluate the safety and efficacy of radiation therapy for stage IVA
      uterine cervical cancer and to identify an optimal radiation regimen. Results:
      Seventeen of the 28 patients developed recurrence after radiation therapy (local
      recurrence in 10 and distant metastasis in 12). The local control and distant
      metastasis-free rates at 3 years in all patients were 61% and 49%, respectively.
      Fourteen patients died after radiation therapy, and all but 2 died of tumor
      progression. The disease-free, cause-specific, and overall survival rates at 3
      years in all patients were 32%, 49%, and 45%, respectively, and the estimated
      median survival time was 32 months. Tumor size (P = 0.007) and involvement in the
      lower third of vagina (P = 0.006) were significant prognostic factors for local
      control. Older age (P = 0.018) and performance status (P = 0.020) were
      significant prognostic factors for distant metastasis. The presence of
      hydronephrosis was the sole significant prognostic factor for survival (P =
      0.026). Only 2 patients developed grade 3 late toxicities (vesicovaginal fistula
      and radiation proctitis, respectively). Materials and Methods: Twenty-eight
      patients with stage IVA uterine cervical cancer received radiation therapy. All
      patients initially received external pelvic irradiation at a median dose of 50.4
      Gy in 28 fractions. Twenty patients also received high-dose-rate intracavitary
      brachytherapy at a median dose of 22 Gy in 4 fractions. These fraction sizes were
      lower than conventional sizes. The total median dose for all 28 patients was 68.7
      Gy. Conclusions: Radiation therapy is safe and effective for treatment of stage
      IVA uterine cervical cancer. The reduced radiation dose per fraction may
      contribute to the prevention of vesicovaginal fistula formation.

PMID- 29348872
TI  - Gene expression profiling reveals U1 snRNA regulates cancer gene expression.
AB  - U1 small nuclear RNA (U1 snRNA), as one of the most abundant ncRNAs in human
      cells, plays an important role in splicing of pre-mRNAs. Compared to previous
      studies which have focused on the primary function of U1 snRNA and the
      neurodegenerative diseases caused by abnormalities of U1 snRNA, this study is to
      investigate how U1 snRNA over-expression affects the expression of mammal genes
      on a genome-wide scale. By comparing the gene expression profiles of U1 snRNA
      over-expressed cells with those of their controls using microarray experiments,
      916 genes or loci were identified significantly Differentially Expressed (DE).
      These 595 up-regulated DE genes and 321 down-regulated DE genes were analyzed
      using annotations from GO categories and pathways from the KEGG database. As a
      result, three of 12 enriched pathways were well-known cancer pathways, while the
      other nine pathways were associated to cancers in previous studies. The further
      analysis of 73 genes involved in 12 pathways suggested that U1 snRNA could
      regulate cancer gene expression. The microarray data under the GEO Series
      accession number GSE84304 is available in the NCBI GEO database.

PMID- 29348873
TI  - Impaired epidermal Langerhans cell maturation in TGFbeta-inducible early gene 1
      (TIEG1) knockout mice.
AB  - TGF-beta-inducible early gene 1 (TIEG1), also known as Kruppel-like factor 10
      (Klf10), represents a major downstream transcription factor of transforming
      growth factor-beta1 (TGF-beta1) signaling. Epidermal Langerhans cells (LCs), a
      unique subpopulation of dendritic cells (DC), essentially mediates immune
      surveillance and tolerance. TGF-beta1 plays a pivotal role in LC maintenance and
      function after birth, although the underpinning mechanisms remain elusive. Here,
      we hypothesized that TIEG1 might be involved in TGF-beta1-mediated LC homeostasis
      and function. Utilizing TIEG1 null mice, we discovered that TIEG1 deficiency did
      not alter LC homeostasis at the steady state and LC repopulation at inflamed
      state, as well as their antigen-uptake capacity, but significantly impaired their
      maturation ability, which was opposite to the fact that loss of TGF-beta1 induced
      spontaneous LC maturation. Moreover, the ablation of TIEG1 enhanced skin contact
      hypersensitivity response. Our results suggested that TIEG1 is not a key molecule
      involved in TGF-beta1-mediated homeostasis, while TIEG1-related signaling
      pathways regulate LC maturation and their function.

PMID- 29348874
TI  - Value of CT-MRI fusion in iodine-125 brachytherapy for high-grade glioma.
AB  - Purposes: To develop a fast, accurate and robust method of fusing Computed
      Tomography (CT) with pre-operative Magnetic Resonance Imaging (MRI) and evaluate
      the impact of using the fused data on the implantation of Iodine-125 (125I) seeds
      for brachytherapy of high-grade gliomas (HGG). Methods: A study was performed on
      a cohort of 10 consecutive patients with HGG were treated by 125I brachytherapy
      with CT-MRI fusion image guided (CMGB), and 10 patients treated with CT alone
      guided (CGB). Statistical analysis was performed to compare (1) the planning
      target volume, (2) the accuracy of location of catheters, (3) the target volume
      covered by 150% prescribe dose (V150), (4) the target volume covered by 200%
      prescribe dose (V200), and (5) the conformity index (CI) with or without fused
      data. Results: The median planning target volume was 50.1 cm3 in CGB, and 56.25
      cm3 in CMGB with significant difference (p = 0.005). The accuracy of catheter
      insertion was 94.4% with CMGB and 78.9% with CGB. The median V150 and V200 was
      45.32% vs 64.24% and 32.81% vs 53.17% in CGB and CMGB, respectively. There was
      significant difference for CI (83.5% vs. 74.5%, p < 0.05) in the two groups for
      the post-operative verification. Conclusions: The proposed MRI-CT fusion method
      enables a quantitative assessment of impact on HGG brachytherapy. The additional
      information obtained from the fused images can be utilized for more accurate
      delineation of lesion boundaries and targeting of catheters. Experimental results
      show that the fusion algorithm is robust and reliable in clinical practice.

PMID- 29348875
TI  - Radiosensitization of the PI3K inhibitor HS-173 through reduction of DNA damage
      repair in pancreatic cancer.
AB  - Activation of PI3K/AKT pathway occurs frequently in tumors and is correlated with
      radioresistance. The PI3K/AKT pathway can be an important target for improvement
      of radiotherapy. Although adding of chemotherapy to radiation therapy regimen
      enhances survival in patients with locally advanced pancreatic cancer, more
      effective therapies for increasing radiosensitivity are urgently needed. In this
      study, we investigated whether the novel PI3K inhibitor HS-173 could attenuate
      radiation-induced up-regulation of DNA damage repair processes and assessed its
      efficacy as a radio- and chemo-sensitizer. Radiosensitizing effects of HS-173
      were tested in human pancreatic cells using clonogenic survival and growth
      assays. Mechanisms underlying the effects of HS-173 and radiation were determined
      by assessing cell cycle and DNA damage- repair pathway components, including
      ataxia-telangiectasia mutated (ATM) and DNA-dependent protein kinase catalytic
      subunit (DNA-PKcs). The in vivo efficacy of HS-173 in cancer radiotherapy was
      evaluated using a human tumor xenograft model. HS-173 significantly increased the
      sensitivity of pancreatic cancer cells to radiation, an effect that was
      associated with G2/M cell cycle arrest. HS-173 also significantly attenuated DNA
      damage repair by potently inhibiting ATM and DNA-PKcs, the two major kinases that
      respond to radiation-induced DNA double-strand breaks (DSBs), resulting in
      sustained DNA damage. Moreover, the combination of HS-173 and radiation delayed
      tumor growth and impaired DNA repair in a pancreatic cancer xenograft model,
      reflecting enhanced radiosensitization. These results showed that HS-173
      significantly improved radiotherapy by inhibiting the DNA damage-repair pathway
      in pancreatic cancer. We therefore suggest that HS-173 may be an effective
      radiosensitizer for pancreatic cancer.

PMID- 29348876
TI  - Genome-wide transcriptional profiling identifies potential signatures in
      discriminating active tuberculosis from latent infection.
AB  - To better understand the host immune response involved in the progression from
      latent tuberculosis infection (LTBI) to active tuberculosis (TB) and identify the
      potential signatures for discriminating TB from LTBI, we performed a genome-wide
      transcriptional profile of Mycobacterium tuberculosis (M.TB)-specific antigens
      stimulated peripheral blood mononuclear cells (PBMCs) from patients with TB, LTBI
      individuals and healthy controls (HCs). A total of 209 and 234 differentially
      expressed genes were detected in TB vs. LTBI and TB vs. HCs, respectively.
      Nineteen differentially expressed genes with top fold change between TB and the
      other 2 groups were validated using quantitative real-time PCR (qPCR), and showed
      94.7% consistent expression pattern with microarray test. Six genes were selected
      for further validation in an independent sample set of 230 samples. Expression of
      the resistin (RETN) and kallikrein 1 (KLK1) genes showed the greatest difference
      between the TB and LTBI or HC groups (P < 0.0001). Receiver operating
      characteristic curve (ROC) analysis showed that the areas under the curve (AUC)
      for RETN and KLK1 were 0.844 (0.783-0.904) and 0.833 (0.769-0.897), respectively,
      when discriminating TB from LTBI. The combination of these two genes achieved the
      best discriminative capacity [AUC = 0.916 (0.872-0.961)], with a sensitivity of
      71.2% (58.7%-81.7%) and a specificity of 93.6% (85.7%-97.9%). Our results provide
      a new potentially diagnostic signature for discriminating TB and LTBI and have
      important implications for better understanding the pathogenesis involved in the
      transition from latent infection to TB activation.

PMID- 29348877
TI  - Role of IRF4 in resistance to immunomodulatory (IMid) compounds(r) in
      Waldenstrom's macroglobulinemia.
AB  - Background: Immunomodulatory drugs, IMid compounds, are active in Waldenstrom's
      macroglobulinemia (WM), although in a lesser extent than multiple myeloma, where
      it was initially developed. We hypothesized WM tumour cells might develop
      mechanisms of resistance, and sought to identify and describe these mechanisms.
      Material and Method: MM and WM-derived cell lines, and Waldenstrom's CD19+ cells
      were treated using both lenalidomide and pomalidomide. Stable CRBN expressing
      cells were generated. Results: WM-derived cells were resistant to IMid compounds.
      We demonstrated a modulation of the downstream targets of IRF4, despite low
      expression of cereblon, and hypothesized IRF4 was the cause for resistance to
      IMid compounds. We ruled out the role of various IRF4 regulatory mechanisms, and
      other pathways activating WM tumor cells, such as B cell activators. Conclusion:
      This study demonstrated that mechanisms of resistance to IMid compounds could be
      not related to cereblon. IRF4 was identified as the potential mechanism of
      resistance to lenalidomide and pomalidomide in WM. It potentially explains the
      lesser activity observed in the clinic in WM. Interestingly, some WM patients
      benefited strongly to lenalidomide and pomalidomide, and future studies will have
      to describe the indirect mechanisms of IMid compounds in WM, possibly related to
      an immune-mediated process.

PMID- 29348878
TI  - Identification of cancer prognosis-associated functional modules using
      differential co-expression networks.
AB  - The rapid accumulation of cancer-related data owing to high-throughput
      technologies has provided unprecedented choices to understand the progression of
      cancer and discover functional networks in multiple cancers. Establishment of co
      expression networks will help us to discover the systemic properties of
      carcinogenesis features and regulatory mechanisms of multiple cancers. Here, we
      proposed a computational workflow to identify differentially co-expressed gene
      modules across 8 cancer types by using combined gene differential expression
      analysis methods and a higher-order generalized singular value decomposition.
      Four co-expression modules were identified; and oncogenes and tumor suppressors
      were significantly enriched in these modules. Functional enrichment analysis
      demonstrated the significantly enriched pathways in these modules, including ECM
      receptor interaction, focal adhesion and PI3K-Akt signaling pathway. The top
      ranked miRNAs (mir-199, mir-29, mir-200) and transcription factors (FOXO4, E2A,
      NFAT, and MAZ) were identified, which play an important role in deregulating
      cellular energetics; and regulating angiogenesis and cancer immune system. The
      clinical significance of the co-expressed gene clusters was assessed by
      evaluating their predictability of cancer patients' survival. The predictive
      power of different clusters and subclusters was demonstrated. Our results will be
      valuable in cancer-related gene function annotation and for the evaluation of
      cancer patients' prognosis.

PMID- 29348879
TI  - Loss of NEIL3 DNA glycosylase markedly increases replication associated double
      strand breaks and enhances sensitivity to ATR inhibitor in glioblastoma cells.
AB  - DNA endonuclease eight-like glycosylase 3 (NEIL3) is one of the DNA glycosylases
      that removes oxidized DNA base lesions from single-stranded DNA (ssDNA) and non-B
      DNA structures. Approximately seven percent of human tumors have an altered NEIL3
      gene. However, the role of NEIL3 in replication-associated repair and its impact
      on modulating treatment response is not known. Here, we report that NEIL3 is
      localized at the DNA double-strand break (DSB) sites during oxidative DNA damage
      and replication stress. Loss of NEIL3 significantly increased spontaneous
      replication-associated DSBs and recruitment of replication protein A (RPA). In
      contrast, we observed a marked decrease in Rad51 on nascent DNA strands at the
      replication fork, suggesting that HR-dependent repair is compromised in NEIL3
      deficient cells. Interestingly, NEIL3-deficient cells were sensitive to ataxia
      telangiectasia and Rad3 related protein (ATR) inhibitor alone or in combination
      with PARP1 inhibitor. This study elucidates the mechanism by which NEIL3 is
      critical to overcome oxidative and replication-associated genotoxic stress. Our
      findings may have important clinical implications to utilize ATR and PARP1
      inhibitors to enhance cytotoxicity in tumors that carry altered levels of NEIL3.

PMID- 29348880
TI  - The potential mechanism of extracellular high mobility group box-1 protein
      mediated p53 expression in immune dysfunction of T lymphocytes.
AB  - In the present study, we examined the activity of p53 protein in Jurkat cells
      treated with high mobility group box-1 protein (HMGB1), thereafter we
      investigated the mechanism of extracellular HMGB1 mediated p53 expression in
      immune dysfunction of T lymphocytes. mRNA expression of p53, mdm2, and p21 was
      determined by Real-time reverse transcription-polymerase chain reaction(RT-PCR).
      The apoptotic rate of Jurkat cells was analyzed by flow cytometry. Expressions of
      bcl-2, bax, caspase-3, phosphorylated (p) extracellular signal-regulated kinase
      (ERK)1/2, ERK1/2, p-p38 mitogen-activated protein kinase (MAPK), p38 MAPK, and p
      c-jun amino-terminal kinase (JNK)1/2 and JNK1/2 were simultaneously determined by
      Western blotting. After treatment with HMGB1 (100 ng/ml or 1000 ng/ml), the
      proliferative activity of Jurkat cells was significantly decreased, and a low and
      medium concentration of HMGB1 induced an up-regulation of p53 mRNA, p-p53 and p53
      protein expression. Meanwhile, levels of mdm2 and p21 were elevated by incubated
      with HMGB1 (100 ng/ml) for 24 or 48 hours. Moreover, the proliferation of Jurkat
      cells in response to HMGB1 (100 ng/ml) in the vector group was significantly
      depressed. The bax and caspase-3 levels in p53 shRNA-expressed cells treated with
      HMGB1 (100 ng/ml) was markedly decreased, whereas expression of bcl-2 was
      obviously enhanced. Among ERK1/2, p38 MAPK and JNK1/2 signaling, only p38 MAPK
      pathway could be significantly activated by treatment with HMGB1, and the
      specific inhibitor of p38 MAPK was used, p53 and p-p53 expression induced by
      HMGB1 were significantly down-regulated. Taken together, our data strongly
      indicated that HMGB1 might enhance p53 expression, which was associated with both
      the proliferative activity as well as apoptosis of T cells.

PMID- 29348881
TI  - Allogeneic stem cell transplantation in acute lymphoblastic leukemia patients
      older than 60 years: a survey from the acute leukemia working party of EBMT.
AB  - Hematopoietic stem cell transplantation (HSCT) is being increasingly explored as
      a treatment modality for older patients with acute lymphoblastic leukemia (ALL).
      Yet, concerns regarding the long term outcome of transplantation in older
      patients limit the wide spread applicability of this approach. In this analysis
      we set out to determine the outcome of ALL patients over the age of 60 who
      underwent reduced intensity HSCT. Herein, we present the experience of the acute
      leukemia working party (ALWP) of the EBMT in this age group. We analyzed a cohort
      of 142 patients transplanted in first remission with a median age of 62 (range 60
      76 years) and a median follow-up period of 36 months post-transplant. At 3 years,
      overall survival (OS) and leukemia-free survival were 42% and 35%, respectively.
      Multivariate analyses identified cytomegalovirus (CMV) donor-recipient matching
      (CMV D+/R+) to be significantly associated with inferior OS. Patients
      transplanted from unrelated donors experienced increased grade II-IV acute graft
      versus host disease compared to those receiving grafts from matched related
      donors [Hazard ratio (HR) of 3.7, 95% confidence interval (CI), 1.75-7.8; p =
      0.0005). Outcome was not impacted by Philadelphia chromosome status. A select
      subset of older ALL patients will benefit from extended survival and a disease
      free state following HSCT.

PMID- 29348882
TI  - MicroRNA203a suppresses glioma tumorigenesis through an ATM-dependent interferon
      response pathway.
AB  - Glioblastoma (GBM) is a deadly and incurable brain tumor. Although microRNAs
      (miRNAs) play critical roles in regulating the cancer cell phenotype, the
      underlying mechanisms of how they regulate tumorigenesis are incompletely
      understood. We previously showed that miR-203a is expressed at relatively low
      levels in GBM patients, and ectopic miR-203a expression in GBM cell lines
      inhibited cell proliferation and migration, increased sensitivity to apoptosis
      induced by interferon (IFN) or temozolomide in vitro, and inhibited GBM
      tumorigenesis in vivo. Here we show that ectopic expression of miR-203a in GBM
      cell lines promotes the IFN response pathway as evidenced by increased IFN
      production and IFN-stimulated gene (ISG) expression, and high basal tyrosine
      phosphorylation of multiple STAT proteins. Importantly, we identified that miR
      203a directly suppressed the protein levels of ataxia-telangiectasia mutated
      (ATM) kinase that negatively regulates IFN production. We found that high ATM
      expression in GBM correlates with poor patient survival and that ATM expression
      is inversely correlated with miR-203a expression. Knockout of ATM expression and
      inhibition of ATM function in GBM cell lines inhibited cell proliferation and
      migration, increased sensitivity to apoptosis induced by therapeutic agents in
      vitro, and markedly suppressed GBM tumor growth and promoted animal survival. In
      contrast, restoring ATM levels in GBM cells ectopically expressing miR-203a
      increased tumorigenicity and decreased animal survival. Our study suggests that
      low miR-203a expression in GBM suppresses the interferon response through an ATM
      dependent pathway.

PMID- 29348883
TI  - Spatial habitats from multiparametric MR imaging are associated with signaling
      pathway activities and survival in glioblastoma.
AB  - Glioblastoma (GBM) show significant inter- and intra-tumoral heterogeneity,
      impacting response to treatment and overall survival time of 12-15 months. To
      study glioblastoma phenotypic heterogeneity, multi-parametric magnetic resonance
      images (MRI) of 85 glioblastoma patients from The Cancer Genome Atlas were
      analyzed to characterize tumor-derived spatial habitats for their relationship
      with outcome (overall survival) and to identify their molecular correlates (i.e.,
      determine associated tumor signaling pathways correlated with imaging-derived
      habitat measurements). Tumor sub-regions based on four sequences (fluid
      attenuated inversion recovery, T1-weighted, post-contrast T1-weighted, and T2
      weighted) were defined by automated segmentation. From relative intensity of
      pixels in the 3-dimensional tumor region, "imaging habitats" were identified and
      analyzed for their association to clinical and genetic data using survival
      modeling and Dirichlet regression, respectively. Sixteen distinct tumor sub
      regions ("spatial imaging habitats") were derived, and those associated with
      overall survival (denoted "relevant" habitats) in glioblastoma patients were
      identified. Dirichlet regression implicated each relevant habitat with unique
      pathway alterations. Relevant habitats also had some pathways and cellular
      processes in common, including phosphorylation of STAT-1 and natural killer cell
      activity, consistent with cancer hallmarks. This work revealed clinical relevance
      of MRI-derived spatial habitats and their relationship with oncogenic molecular
      mechanisms in patients with GBM. Characterizing the associations between imaging
      derived phenotypic measurements with the genomic and molecular characteristics of
      tumors can enable insights into tumor biology, further enabling the practice of
      personalized cancer treatment. The analytical framework and workflow demonstrated
      in this study are inherently scalable to multiple MR sequences.

PMID- 29348884
TI  - Alpha-1-antitrypsin functions as a protective factor in preeclampsia through
      activating Smad2 and inhibitor of DNA binding 4.
AB  - Pre-eclampsia (PE) is one of the most common reason for high morbidity and
      mortality of maternal and prenatal infants. Production from oxidative stress
      results in maternal ROS system and anti-oxidation defense system imbalance to
      promote tissue ischemia and hypoxia, and ultimately impairs the maternal organs
      and placenta. Our previous study showed that exogenous Alpha-1-antitrypsin (AAT)
      and overexpression of AAT in umbilical vein cell (HUVEC) hypoxia-reoxygenation
      model could increase the activity of antioxidant enzymes, and played a protective
      role in preeclampsia animal model. In this study, we aim to investigate the
      underlying mechanism by which AAT prevents PE progress. Whole-exome sequencing
      was performed to screen the genes altered by AAT. We found that AAT knockdown
      altered the expression of Smad family and Id family genes, and further
      demonstrated that AAT positively regulated Id4 expression through activating
      Smad2. Reduced Id4 expression and Smad2 phosphorylation were observed in
      preeclampsia animal model, which was also confirmed in human placenta tissues. In
      addition, AAT protected HUVEC cells from hypoxia/reoxygenation injury and
      relieved preeclampsia symptoms through Smad2/Id4 axis. Our data illustrate
      AAT/Smad2/Id4 axis is an important mediator of placenta and vascular function
      during pregnancy. These findings provide insights into events governing pregnancy
      associated disorders, such as preeclampsia.

PMID- 29348885
TI  - Drug-resistance in doxorubicin-resistant FL5.12 hematopoietic cells: elevated
      MDR1, drug efflux and side-population positive and decreased BCL2-family member
      expression.
AB  - Chemotherapeutic drug treatment can result in the emergence of drug-resistant
      cells. By culturing an interleukin-3 (IL-3)-dependent cell line, FL5.12 cells in
      the presence of the chemotherapeutic drug doxorubicin, we isolated FL/Doxo cells
      which are multi-drug resistant. Increased levels of drug efflux were detected in
      FL/Doxo cells which could be inhibited by the MDR1 inhibitor verapamil but not by
      the MRP1 inhibitor MK571. The effects of TP53 and MEK1 were examined by infection
      of FL/Doxo cells with retroviruses encoding either a dominant negative TP-53 gene
      (FL/Doxo+ TP53 (DN) or a constitutively-activated MEK-1 gene (FL/Doxo + MEK1
      (CA). Elevated MDR1 but not MRP1 mRNA transcripts were detected by quantitative
      RT-PCR in the drug-resistant cells while transcripts encoding anti-apoptotic
      genes such as: BCL2, BCLXL and MCL1 were observed at higher levels in the drug
      sensitive FL5.12 cells. The percentage of cells that were side-population
      positive was increased in the drug-resistant cells compared to the parental line.
      Drug-resistance and side-positive population cells have been associated with
      cancer stem cells (CSC). Our studies suggest mechanisms which could allow the
      targeting of these molecules to prevent drug-resistance.

PMID- 29348886
TI  - FRK inhibits breast cancer cell migration and invasion by suppressing epithelial
      mesenchymal transition.
AB  - The human fyn-related kinase (FRK) is a non-receptor tyrosine kinase known to
      have tumor suppressor activity in breast cancer cells. However, its mechanism of
      action has not been fully characterized. We generated FRK-stable MDA-MB-231
      breast cancer cell lines and analyzed the effect on cell proliferation,
      migration, and invasiveness. We also used kinome analysis to identify potential
      FRK-regulated signaling pathways. We employed both immunoblotting and RT-PCR to
      identify/validate FRK-regulated targets (proteins and genes) in these cells.
      Finally, we interrogated the TCGA and GENT gene expression databases to determine
      the correlation between the expression of FRK and epithelial/mesenchymal markers.
      We observed that FRK overexpression suppressed cell proliferation, migration, and
      invasiveness, inhibited various JAK/STAT, MAPK and Akt signaling pathways, and
      suppressed the expression of some STAT3 target genes. Also, FRK overexpression
      increased the expression of epithelial markers including E-cadherin mRNA and down
      regulated the transcript levels of vimentin, fibronectin, and slug. Finally, we
      observed an inverse correlation between FRK expression and mesenchymal markers in
      a large cohort of breast cancer cells. Our data, therefore, suggests that FRK
      represses cell proliferation, migration and invasiveness by suppressing
      epithelial to mesenchymal transition.

PMID- 29348887
TI  - RNA-seq expression profiling of rat MCAO model following reperfusion Orexin-A.
AB  - Orexin-A is a neuropeptide with potent neuroprotective activity towards cerebral
      ischemia-reperfusion (I/R) injury, but few studies have attempted to elucidate
      the mechanism. Herein, we performed global gene expression profiling of the
      hippocampus following reperfusion with Orexin-A using RNA sequencing (RNA-seq).
      RNA-seq identified 649 differentially expressed genes (DEGs) in the Orexin-A
      group compared with saline controls (I/R group), of which 149 were up-regulated
      and 500 were down-regulated. DEGs were confirmed using qRT-PCR, their molecular
      functions, biological processes and molecular components were explored using Gene
      Ontology (GO) analysis and 206 KEGG pathways were associated with Orexin-A
      treatment. MAPK, chemokine and calcium signalling pathways were mainly
      responsible for the neuroprotective effects of Orexin-A. Hspb1, Igf2 and Ptk2b
      were selected for functional interaction analysis by GeneMANIA. The results
      suggest that Orexin-A modifies gene expression in the hippocampus, leading to
      neuroprotection from I/R injury. The study provides a basis for future
      elucidation of the molecular mechanisms underlying Orexin-A.

PMID- 29348888
TI  - The association analysis of TLR2 and TLR4 gene with tuberculosis in the Tibetan
      Chinese population.
AB  - Background: The present study was undertaken to explore the relationship of Toll
      like receptor (TLR) 2, TLR4 genes polymorphisms with Pulmonary tuberculosis (PTB)
      risk in a sample of Chinese population. Methods: For this study, we recruited 467
      subjects with PTB and 504 healthy subjects from a Tibetan population living in
      near or in Xi'an, China. Association analyses of single-nucleotide polymorphisms
      (SNPs) in TLR2 and TLR4 were performed with SPSS Statistics (version 17.0),
      SNPStats, Haploview (version 4.2), and SHEsis software. Results: The research
      results that is association analysis of pulmonary tuberculosis show there are two
      increased-risk SNPs (rs7696323, OR=1.32, 95%CI =1.08-1.62, P= 0.007; rs12377632,
      OR=1.30, 95%CI =1.09-1.55, P= 0.004) and three decreased-risk SNPs (rs3804099,
      OR=0.64, 95%CI =0.52-0.79, P= 1.9510-5; rs3804100, OR=0.67, 95%CI =0.54-0.82, P=
      0.0001; rs11536889, OR=0.54, 95%CI =0.42-0.69, P= 9.1410-7). Conclusions: We
      found that two SNPs are associated with increased PTB risk and three SNPs
      decreased PTB risk in the Chinese Tibetan population. Our findings demonstrate an
      association between TLR2 and TLR4 polymorphisms and PTB.

PMID- 29348889
TI  - Metformin and temozolomide, a synergic option to overcome resistance in
      glioblastoma multiforme models.
AB  - Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor with
      poor survival. Cytoreduction in association with radiotherapy and temozolomide
      (TMZ) is the standard therapy, but response is heterogeneous and life expectancy
      is limited. The combined use of chemotherapeutic agents with drugs targeting cell
      metabolism is becoming an interesting therapeutic option for cancer treatment.
      Here, we found that metformin (MET) enhances TMZ effect on TMZ-sensitive cell
      line (U251) and overcomes TMZ-resistance in T98G GBM cell line. In particular,
      combined-treatment modulated apoptosis by increasing Bax/Bcl-2 ratio, and reduced
      Reactive Oxygen Species (ROS) production. We also observed that MET associated
      with TMZ was able to reduce the expression of glioma stem cells (GSC) marker CD90
      particularly in T98G cells but not that of CD133. In vivo experiments showed that
      combined treatment with TMZ and MET significantly slowed down growth of TMZ
      resistant tumors but did not affect overall survival of TMZ-sensitive tumor
      bearing mice. In conclusion, our results showed that metformin is able to enhance
      TMZ effect in TMZ-resistant cell line suggesting its potential use in TMZ
      refractory GBM patients. However, the lack of effect on a GBM malignancy marker
      like CD133 requires further evaluation since it might influence response
      duration.

PMID- 29348890
TI  - Adoptive immunotherapy shows encouraging benefit on non-small cell lung cancer: a
      systematic review and meta-analysis.
AB  - Although adoptive immunotherapy (AIT) is a novel emerging target treatment for
      non-small cell lung cancer (NSCLC), its actual efficacy remains controversial. In
      this meta-analysis, we aimed to evaluate the efficacy of AIT for NSCLC. We
      systematically searched PubMed, the Cochrane Library, EMBASE, Medline, and Web of
      Science for relevant parallel randomized controlled trials (RCTs) and high
      quality observation studies of AIT without any language restrictions. Two
      investigators reviewed all the texts and extracted information regarding overall
      survival rate (OS), progression-free survival rate (PFS), objective response rate
      (ORR), and disease control rate (DCR) from eligible studies; sensitivity analyses
      and subgroup analyses were also conducted to reduce heterogeneity Of 319 suitable
      studies, 15 studies (13 RCTs and 2 observation studies) involving 1684 patients
      were finally included. Compared to the Control therapy (CT) group, the AIT group
      exhibited better 1-year OS (P = 0.001), 2-year OS (P < 0.001), 3-year OS (P <
      0.001), 5-year OS (P = 0.032), 1-year PFS (P < 0.001), and 2-year PFS (P =
      0.029). The difference in the ORR (P = 0.293) and DCR (P = 0.123) was not
      significant between the groups. The subgroup analysis showed that DC/CIK did more
      benefit to NSCLC patients than LAK and the cycles not associated with AIT
      efficacy. AIT can significantly improve the OS and PFS with acceptable toxicity
      for NSCLC. Nevertheless, further multicenter studies are needed to confirm our
      conclusion and determine which adoptive immunotherapy is associated with the
      greatest efficacy.

PMID- 29348891
TI  - Clinicopathological impacts of high c-Met expression in head and neck squamous
      cell carcinoma: a meta-analysis and review.
AB  - High c-Met expression has been observed in head and neck squamous cell carcinoma
      (HNSCC). However, its clinicopathological impact remains controversial. We
      performed this meta-analysis to evaluate the pathologic and prognostic impacts of
      c-Met overexpression in patients with HNSCC. A systematic computerized search of
      the electronic databases was carried out. From 16 studies, 1,948 patients with
      HNSCC were included in the meta-analysis. Compared with HNSCCs showing low c-Met
      expression, tumors with high c-Met expression were significantly associated with
      higher rate of lymph node metastasis (odds ratio = 3.26, 95% CI: 2.27-4.69, P <
      0.00001) and higher T stage (odds ratio = 1.33, 95% CI: 1.03-1.71, P = 0.03). In
      addition, patients with c-Met-high HNSCC showed significantly worse disease-free
      survival (hazard ratio = 1.49, 95% CI: 1.04-2.14, P = 0.03) and overall survival
      (hazard ratio = 1.83, 95% CI: 1.29-2.60, P = 0.0007) than those with c-Met-low
      tumor. In conclusion, this meta-analysis demonstrates that high c-Met expression
      is significantly associated with worse pathological features and prognosis,
      indicating c-Met overexpression is an adverse prognostic marker for patients with
      HNSCC.

PMID- 29348892
TI  - Association between cadmium exposure and diabetes mellitus risk: a prisma
      compliant systematic review and meta-analysis.
AB  - Cadmium (Cd) is a pollutant with multiple adverse health effects: cancer, renal
      dysfunction, osteoporosis and fracture, and cardiovascular disease. Several
      population-based studies found an association between Cd and diabetes mellitus
      (DM), but this association is inconsistent with other research. We conducted meta
      analysis to examine relationship between urinary/blood Cd exposure and DM risk.
      Pertinent studies were identified by searching PubMed and Embase databases, and
      combined odds ratio (OR) and corresponding 95% confidence interval (CI) were
      applied to evaluate said association. Meta-analysis showed that high U-Cd
      exposure is not correlated with DM risk (OR = 1.19; 95% CI = 0.83-1.71), and high
      B-Cd exposure is also not associated with increased risk of DM (OR = 1.16; 95% CI
      = 0.84-1.62) in the general population. Subgroup and sensitivity analysis proved
      similar results, with little evidence of publication bias. This meta-analysis
      suggests that high U-Cd/B-Cd exposure may not be risk factor for DM in general
      populations. However, large prospective studies are needed to confirm this
      finding.

PMID- 29348893
TI  - Diagnostic accuracy of DNA methylation in detection of gastric cancer: a meta
      analysis.
AB  - Emerging studies demonstrate the diagnostic utility of DNA methylation-based
      blood test for gastric cancer. The aim of the meta-analysis is to evaluate the
      accuracy of blood DNA methylation markers for detecting patients with gastric
      cancer. A systematic literature search to November 2016 that evaluated DNA
      methylation markers utilizing blood specimen to detect gastric cancer were
      selected to derive pooled sensitivities and specificities. 32 studies including
      4,172 patients (gastric cancer (N = 2,098), control (N = 2,074)) met the study
      criteria. Overall sensitivity of DNA methylation-based blood test for detecting
      gastric cancer was 57% (95% CI 50-63%); specificity was 97% (95% CI 95-98%).
      Among patients who received plasma-based testing, sensitivity was 71% (95% CI 59
      81%); specificity was 89% (95% CI 78-94%). Among patients who received serum
      based testing, sensitivity was 50% (95% CI 43-58%); specificity was 98% (95% CI
      96-99%). Using multiple methylated genes had sensitivity of 76% (95% CI 64-84%);
      specificity of 85% (95% CI 65-95%). DNA methylation test had sensitivity of 55%
      (95% CI 47-64%) and specificity of 96% (95% CI 92-98%) for detecting TNM stage
      I+II gastric cancer. In conclusion, blood-based DNA methylation test had high
      specificity but modest sensitivity for detecting gastric cancer. Evaluating
      multiple methylated genes or using plasma sample may improve the diagnostic
      sensitivity.

PMID- 29348894
TI  - The efficacy and safety of tivantinib in the treatment of solid tumors: a
      systematic review and meta-analysis.
AB  - Background: Tivantinib was designed to kill cancers by targeting the mesenchymal
      epithelial transition (MET) protein. Although numerous tivantinib clinical trials
      are ongoing, tivantinib's efficacy and safety are still not clear. This meta
      analysis was done to evaluate tivantinib's efficacy and safety in solid tumor
      treatment. Materials and Methods: PUBMED, EMBASE, and other databases were
      searched for eligible tivantinib clinical trials. The hazard ratio (HR) and 95%
      confidence interval (CI) of progression-free and overall survival (PFS and OS,
      respectively) were pooled and analyzed to evaluate tivantinib's efficacy. Data
      concerning adverse events (Grade >= 3) were pooled to calculate relative risks
      (RRs) with 95% CI for tivantinib-treated compared with control arms. Findings:
      Patients (1824) from six randomized control trials (RCTs) were enrolled. Compared
      with controls, tivantinib produced a significant improvement in PFS (HR, 0.73;
      95% CI 0.65-0.83) but not in OS. In the non-small-cell lung cancer (NSCLC)
      subgroup, tivantinib combined with erlotinib prolonged patients' PFS when
      compared with controls (HR, 0.75; 95% CI, 0.65-0.86). In the white population,
      tivantinib also significantly improve PFS between treatment and control arms (HR,
      0.75; 95% CI, 0.65-0.87). Tivantinib significantly improved OS in patients with
      high levels of MET expression. Tivantinib was shown to increase the risk of
      anemia and neutropenia. Interpretation: Tivantinib was better in prolonging PFS
      (not OS) in patients with solid tumors. High MET expression cancers may benefit
      from tivantinib. Tivantinib appeared to be well-tolerated by patients.

PMID- 29348895
TI  - Upregulated SOX9 expression indicates worse prognosis in solid tumors: a
      systematic review and meta-analysis.
AB  - It was recently reported that increased SOX9 expression drives tumor growth and
      promotes cancer invasion during human tumorigenicity and metastasis. However, the
      prognostic value of SOX9 for the survival of patients with solid tumors remains
      controversial. The present meta-analysis was thus performed to highlight the link
      between dysregulated SOX9 expression and prognosis in cancer patients. A
      systematic literature search was conducted using the electronic databases PubMed,
      Web of Science and Embase to identify eligible studies. A random-effects meta
      analytical model was employed to correlate SOX9 expression with overall survival
      (OS), disease-free survival (DFS) and clinicopathological features. In total, 17
      studies with 3307 patients were eligible for the final analysis. Combined hazard
      ratios (HRs) and 95% confidence intervals (CIs) suggested that high SOX9
      expression has an unfavourable impact on OS (HR = 1.66, 95% CI 1.36-2.02, P <
      0.001) and DFS (HR = 3.54, 95% CI 2.29-5.47, P = 0.008) in multivariate analysis.
      Additionally, the pooled odds ratios (ORs) indicated that SOX9 over-expression is
      associated with large tumor size, lymph node metastasis, distant metastasis and a
      higher clinical stage. Overall, these results indicated that SOX9 over-expression
      in patients with solid tumors might be related to poor prognosis and could serve
      as a potential predictive marker of poor clinicopathological prognosis factor.

PMID- 29348896
TI  - Prognostic value of long non-coding RNA PVT1 as a novel biomarker in various
      cancers: a meta-analysis.
AB  - Background: Plasmacytoma variant translocation 1 (PVT1) has recently been
      reported to be aberrantly expressed and serves as a prognostic biomarker in many
      types of cancers. However, its prognostic significance remains controversial.
      Here, we conducted a meta-analysis to investigate the prognostic value of PVT1
      expression in cancers. Results: A total of 2109 patients from 20 studies were
      included. The results showed that elevated PVT1 expression predicted a poor
      outcome for overall survival (OS) in nine types of cancers (HR = 1.40, 95% CI:
      1.21-1.59). Subgroup analysis indicated that there was a significant association
      between PVT1 overexpression and poor OS of patients with gastric cancer,
      gynecology cancer and lung cancer. Furthermore, we also found a negative
      significant relationship between PVT1 expression and disease-free survival (HR =
      1.83, 95% CI: 1.39-2.27), progression-free survival (HR = 1.63, 95% CI: 1.34
      1.93) and recurrence-free survival (HR = 1.74, 95% CI: 1.01-2.47). In addition,
      the level of PVT1 expression was positively related to tumor size, TNM stage,
      lymph node metastasis and distant metastases. Materials and Methods: A systematic
      search was performed through the PubMed, EMBASE, Web of Science, Ovid and
      Cochrane library databases for eligible studies on prognostic value of PVT1 in
      cancers from inception up to June, 2017. The pooled hazard ratios (HRs) or odds
      ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the
      association between PVT1 expression and clinical outcomes. Conclusions: PVT1
      expression positively related to tumor size, TNM stages, lymph node metastasis
      and distant metastases, and served as a prognostic biomarker in different types
      of cancers.

PMID- 29348897
TI  - Interferon-alpha adjuvant therapy decreases the recurrence of early clear cell
      renal cell carcinoma and improves the prognosis of Chinese patients.
AB  - The survival time of patients with early clear cell renal cell carcinoma (ccRCC)
      is fairly long, but 20% to 30% of patients with localized tumors experience
      relapse, and the effect of IFN-alpha on survival has not been well studied in
      patients with early ccRCC. In this study, 208 patients with early ccRCC were
      treated with surgery, and 54 of the patients received IFN-alpha as adjuvant
      therapy. The remaining 115 patients were treated with surgery but not with IFN
      alpha therapy. The primary endpoint was the recurrence rate, 20.37% (11/54) and
      33.04% (38/115) in the IFN-alpha and surgery-only group, respectively. The
      secondary endpoint was progression-free survival (PFS), which was 123.70 (95% CI:
      107.18-140.22) months for the IFN-alpha group, and 95.80 (95% CI: 82.18-109.42)
      months for the non-IFN-alpha group; this difference was significant (P < 0.05).
      The main side effects were pyrexia (61.11%), muscle pain (24.07%), malaise
      (9.26%), anorexia (5.56%), hepatic dysfunction (3.70%) and renal dysfunction
      (1.85%). Moreover, a multivariate regression identified older age, higher BMI
      index and smoking as significant and independent predictors of decreased PFS (P <
      0.05). Overall, IFN-alpha therapy significantly improved PFS in Chinese patients
      with early ccRCC and was an independent prognostic factor (P < 0.05). In
      conclusion, our study showed that adjuvant IFN-alpha therapy decreased the
      recurrence rate and prolonged PFS in patients with ccRCC. Thus, this treatment
      may help clinicians to select a better treatment modality and better predict
      survival in these patients.

PMID- 29348898
TI  - Avoiding thermal injury during near-infrared photoimmunotherapy (NIR-PIT): the
      importance of NIR light power density.
AB  - Near-infrared photoimmunotherapy (NIR-PIT) is a newly-established cancer
      treatment which employs the combination of an antibody-photoabsorber conjugate
      (APC) and NIR light. When NIR light is absorbed by APC-bound tissues, a certain
      amount of heat is generated locally. For the most part this results in a
      subclinical rise in skin temperature, however, excessive light exposure may cause
      non-specific thermal damage. In this study, we investigated the potential for
      thermal damage caused by NIR-PIT by measuring surface temperature. Two sources of
      light, laser and light emitting diode (LED), were compared in a mouse tumor
      model. First, we found that the skin was heated rapidly by NIR light regardless
      of whether laser or LED light sources were used. Air cooling at the surface
      reduced the rise in temperature. There were no associations between the rise of
      skin temperature and tumor volume of the treated tumor, or APC concentration.
      Second, we investigated the extent of thermal damage to the skin at various light
      doses. We detected burn injuries 1 day after NIR-PIT, when the NIR light was at a
      power density higher than 600 mW/cm2. Successful treatments at lower power
      density could be achieved if the total light energy absorbed by the tumor was the
      same, i.e. by extending the duration of light exposure. In conclusion, this study
      demonstrates that thermal injury after NIR-PIT can be avoided by either employing
      a cooling system or by lowering the power density of the light source and
      prolonging the exposure time such that the total energy is constant. Thus,
      thermal damage is preventable side effect of NIR-PIT.

PMID- 29348899
TI  - Curative versus palliative treatments for colorectal cancer with peritoneal
      carcinomatosis: a systematic review and meta-analysis.
AB  - The objective of this study was to provide an up-to-date summary of the current
      evidence that may be useful for updating guidelines. We comprehensively searched
      the published literatures and conferences for studies that compared curative with
      palliative treatments in colorectal cancer patients with peritoneal metastasis.
      The primary outcomes considered in this study were three- and five-year overall
      survival rates. We pooled data across studies and estimated summary effect sizes.
      Overall, patients who received curative treatments had improved three-year
      survival (hazard ratio (HR), 2.19 [95% CI, 1.83 to 2.62]) and five-year survival
      (HR, 2.22 [95% CI, 1.83 to 2.69]) compared with those who received palliative
      treatments. Patients who received curative treatments had an increased risk of
      treatment-related morbidity (odds ratio (OR), 2.90 [95% CI, 2.02 to 4.17]), but
      there was no significant difference in treatment-related mortality between
      patients who received curative treatments and those who received palliative
      treatments (OR, 1.46 [CI, 0.62 to 3.47]). Curative treatments improved overall
      survival in colorectal cancer patients with peritoneal metastasis and did not
      increase the risk of treatment-related mortality. Curative treatments were
      associated with a higher risk of treatment-related morbidity. These data
      highlight the importance for further investigation aimed at prevention of
      treatment-associated morbidity.

PMID- 29348900
TI  - Validation of risk prediction models for the development of HBV-related HCC: a
      retrospective multi-center 10-year follow-up cohort study.
AB  - Recently, modified REACH-B (mREACH-B) risk prediction model for hepatocellular
      carcinoma (HCC) development was proposed. We validated the accuracy of the mREACH
      B model and compared its accuracy with those of other prediction models. Between
      2006 and 2012, 1,241 patients with chronic hepatitis B (CHB) were recruited. All
      patients underwent transient elastography at enrollment. The median age of the
      study population (840 males, 401 females) was 49 years. The median PAGE-B, LSM
      HCC, and mREACH-B values were 10, 10, and 8, respectively. Among patients without
      cirrhosis (n = 940, 75.7%), the median REACH-B value was 9. During the follow-up
      period (median 77.4 months), 66 (5.3%) and 83 (6.7%) patients developed HCC and
      liver-related events (LRE), respectively. Higher liver stiffness (LS)
      independently predicted HCC (hazard ratio [HR] = 1.047) and LRE development (HR =
      1.047) (all P < 0.05). The mREACH-B significantly predicted HCC (AUC = 0.824 at 3
      year and 0.750 at 5-year) and LRE development (AUC = 0.782 at 3-year and 0.739 at
      5-year) (all P < 0.001) and it performed similarly or significantly better than
      the PAGE-B and LSM-HCC (AUC = 0.715-0.809 at 3-year and 0.719-0.742 at 5-year for
      HCC; AUC = 0.704-0.777 at 3-year and 0.721-0.735 at 5-year for LRE). Among
      patients without cirrhosis, mREACH-B predicted HCC (AUC = 0.803 vs. 0.654-0.816
      at 3-year and 0.684 vs. 0.639-0.738 at 5-year) and LRE development (AUC = 0.734
      vs. 0.619-0.789 at 3-year and 0.674 vs. 0.626-0.729 at 5-year) similarly to PAGE
      B, REACH-B, and LSM-HCC. mREACH-B appropriately predicted HCC and LRE development
      in patients with CHB and showed similar or superior accuracy to those of PAGE-B,
      REACH-B, and LSM-HCC.

PMID- 29348901
TI  - Prevalence and risk factors of lower urinary tract symptoms in Chinese adult men:
      a multicentre cross-sectional study.
AB  - There has been no previous population-based study reporting the prevalence and
      risk factors of male lower urinary tract symptoms (LUTS) among men in mainland
      China. This cross-sectional study was conducted from 2013 to 2014 in three
      representative provinces of China: Guangdong, Hubei and Jiangsu. 3250 individuals
      participated in the interviews, which involved a questionnaire covering
      sociodemographic characteristics, lifestyle, dietary patterns and the
      International Prostate Symptom Score (IPSS). Blood was collected for lipids,
      glucose, insulin and reproductive hormone tests. The incidences of LUTS and its
      obstructive and irritative symptoms were calculated. Risk factors for LUTS were
      identified using multivariable logistic regression analysis. The prevalence of
      moderate to severe LUTS and its obstructive and irritative symptoms was 14.3%,
      13.1% and 16.1%, respectively, and increased with age. The prevalence in
      Guangdong was much lower than that in Hubei and Jiangsu in different ages.
      Increased fasting plasma glucose and decreased HDL-C levels were associated with
      an increased risk of moderate to severe LUTS (OR = 1.30, 95% CI: 1.02-1.65 and OR
      = 2.06, 95% CI: 1.08-3.94, respectively). Free testosterone < 0.22 ng/ml
      decreased the risk of moderate to severe LUTS and obstructive and irritative
      symptoms by about 20-30%. An inadequate daily intake of vegetables, fruit and
      water significantly increased the risk of LUTS by 1.3-to 2.0 times. In
      conclusion, the prevalence of LUTS in Chinese men is high and increases with age.
      Dietary patterns may be critical for the development of LUTS. Thus, dietary
      modifications could be a useful strategy for preventing the development of LUTS.

PMID- 29348902
TI  - Feasibility and outcome of primary laparoscopic cytoreductive surgery for
      advanced epithelial ovarian cancer: a comparison to laparotomic surgery in
      retrospective cohorts.
AB  - Objectives: To assess the feasibility and outcome of primary laparoscopic
      cytoreductive surgery on advanced epithelial ovarian cancer in comparison with
      conventional open surgery. Materials and Methods: Patients undergoing primary
      laparoscopic cytoreductive surgery (LCS) from March 2007 to December 2016 were
      matched to controls treated with laparotomic cytoreduction during the same
      period. Procedural data and outcomes were analyzed. Results: The LCS group (n =
      64) and laparotomic group (n = 68) had similar age, BMI, stages, histologic type
      and grading. The LCS group exhibited significantly less operating time (P <
      0.001), less intraoperative blood loss (P < 0.001), and shorter time to recover
      postoperatively (P = 0.002). No statistical difference was observed for the
      number of pelvic and para-aortic lymph nodes dissected (P = 0.326 and P = 0.151).
      Significant difference was observed in satisfaction of the cytoreduction (95.3%
      vs. 76.5%, P = 0.008). No significant difference were observed either in intra
      operative or in post-operative complications between the two groups (P = 0.250).
      Three patients in the LCS group experienced intra-operative complications (4.7%)
      and were all treated laparoscopically. The conversion rate was 3.1%. No
      significant differences were observed in the progression-free survival and
      overall survival between the two groups during the medium follow-up of 18 months
      (P = 0.236 and P = 0.216). The 2-year and 3-year progression-free survival was
      67.9%, 55.5% in LCS group and 53.8%, 33.3% respectively in the control group. The
      2-year and 3-year overall survival was 95.8%, 88.7% respectively in the LCS group
      and 89.0%, 83.7% in the control group. Conclusions: Primary laparoscopic
      cytoreductive surgery in some strictly selected advanced stages of EOC patients
      was feasible and safe, resulting in oncologic outcomes not inferior to those in
      open surgery.

PMID- 29348903
TI  - The systemic inflammation-based Glasgow Prognostic Score as a powerful prognostic
      factor in patients with upper tract urothelial carcinoma.
AB  - Introduction and Objective: The combination of C-reactive protein and albumin,
      the Glasgow Prognostic Score (GPS), had independent prognostic value in patients
      with varying cancers, except for upper tract urothelial carcinoma (UTUC). The aim
      of this study was to describe the relationship between GPS and survival in
      patients with UTUC after adjustment for other prognostic factors. Materials and
      Methods: We queried 2 UTUC databases. Retrospective clinical series on patients
      with localized UTUC managed by nephroureterectomy with bladder cuff, for whom
      data from the Yamaguchi Uro-Oncology Group and Osaka Medical College registry,
      including age, presence of bladder cancer, pT stage, lymphovascular invasion, C
      reactive protein (CRP) and albumin, were analyzed. The GPS was constructed by
      combining CRP and albumin. Cancer specific survival (CSS) and overall survival
      (OS) and relative excess risk of death were estimated by GPS categories after
      adjusting for gender, age, ECOG performance status (PS), grade, and
      lymphovascular invasion (LVI). Results: Seven hundred and twenty four UTUC
      patients were identified. Our final cohort included 574 patients; of these, 29.2%
      died during a maximum follow up of 16.7 years. The estimated mean 10-year CSS of
      patients with GPS of scre-0, -1, and -2 was 99.5, 95.1, and 75.9 months,
      respectively. Patients with GPS of score-2 had poorest 10-year estimated mean OS
      of 67.6 months (57.2-77.9). Raised GPS also had a significant association with
      excess risk of cancer death at 10 years (GPS 2: Relative Excess Risk = 1.74, 95%
      CI 1.20-2.54) after adjusting for gender, patients' age, ECOG PS, and tumor
      focality. C-index of GPS both for CSS and OS were superior to patients' age and
      tumor focality, and comparable to grade. Conclusions: The GPS is an independent
      prognostic factor for CSS and OS after surgery with curative intent for localized
      UTUC. It significantly increases the accuracy of established prognostic factors.
      The GPS may provide a meaningful adjunct for patient counseling and clinical
      trial design.

PMID- 29348904
TI  - Role of tissue-type plasminogen activator and plasminogen activator inhibitor-1
      in psychological stress and depression.
AB  - Major depressive disorder is a common illness worldwide, but the pathogenesis of
      the disorder remains incompletely understood. The tissue-type plasminogen
      activator-plasminogen proteolytic cascade is highly expressed in the brain
      regions involved in mood regulation and neuroplasticity. Accumulating evidence
      from animal and human studies suggests that tissue-type plasminogen activator and
      its chief inhibitor, plasminogen activator inhibitor-1, are related to stress
      reaction and depression. Furthermore, the neurotrophic hypothesis of depression
      postulates that compromised neurotrophin brain-derived neurotrophic factor (BDNF)
      function is directly involved in the pathophysiology of depression. In the brain,
      the proteolytic cleavage of proBDNF, a BDNF precursor, to mature BDNF through
      plasmin represents one mechanism that can change the direction of BDNF action. We
      also discuss the implications of tissue-type plasminogen activator and
      plasminogen activator inhibitor-1 alterations as biomarkers for major depressive
      disorder. Using drugs that increase tissue-type plasminogen activator or decrease
      plasminogen activator inhibitor-1 levels may open new avenues to develop
      conceptually novel therapeutic strategies for depression treatment.

PMID- 29348906
TI  - An ANK1 IVS3-2A>C mutation causes exon 4 skipping in two patients from a Chinese
      family with hereditary spherocytosis.
AB  - Hereditary spherocytosis (HS) is a congenital hemolytic anemia that affects the
      cell membrane of red blood cells and is characterized by the presence of
      spherical-shaped erythrocytes in the peripheral blood film. The clinical
      manifestation of HS ranges from asymptomatic to severe cases that require
      transfusion during early childhood. HS is caused by mutations in red blood cell
      membrane protein encoding genes, including ANK1, EPB42, SLC4A1, SPTA1, and SPTB.
      Mutations of the ANK1 gene account for 75% of all HS cases, and these particular
      mutations are typically inherited in an autosomal dominant manner. In this study,
      heterozygous an ANK1 IVS3-2A>C mutation was identified in a 7-year-old girl with
      Coombs-negative and severe hemolytic jaundice using targeted next-generation
      sequencing (NGS) and Sanger sequencing. Spherocytes were observed in a peripheral
      smear. Osmotic fragility was increased, and glucose-6-phosphate dehydrogenase
      (G6PD) activity was normal. A genetic mutation screen for alpha- and beta
      thalassemia was negative. Autoimmune antibody tests were negative. Both the girl
      and her affected father received a splenectomy. Patient-derived peripheral blood
      mononuclear cells showed skipping of exon 4 in the mRNA, which confirmed the
      splicing mutation effect of the ANK1 IVS3-2A>C mutation. Moreover, the anemia was
      ameliorated after splenectomy. Our results demonstrate that the ANK1 IVS3-2A>C
      mutation may lead to exon 4 skipping of the ANK1 gene and cause HS.

PMID- 29348905
TI  - Bridging the divide: preclinical research discrepancies between triple-negative
      breast cancer cell lines and patient tumors.
AB  - Triple-negative breast cancer (TNBC) is the most refractory subtype of breast
      cancer and disproportionately accounts for the majority of breast cancer related
      deaths. Effective treatment of this disease remains an unmet medical need. Over
      the past several decades, TNBC cell lines have been used as the foundation for
      drug development and disease modeling. However, ever-mounting research
      demonstrates striking differences between cell lines and clinical TNBC tumors,
      disconnecting bench research and actual clinical responses. In this review, we
      discuss the limitations of cell lines and the importance of using patients'
      tumors for translational research, and highlight the usage of patient-derived
      xenograft (PDXs) models that have emerged as a clinically relevant platform for
      preclinical studies. PDX tumors possess tumor heterogeneity with similar
      cellular, molecular, genetic and epigenetic properties akin to those found within
      patients' tumors. Moreover, PDX and clinical tumors possess abnormal vasculature
      with higher blood vessel permeability, a feature that is not always demonstrated
      in in vivo cell line xenografts. Development of clinically relevant, novel drug
      nanoparticles capable of accumulating in PDX tumors through the enhanced
      permeability and retention effect in tumor vasculature may lead to new and
      effective TNBC treatments.

PMID- 29348907
TI  - Microsatellite stability and mismatch repair proficiency in nasopharyngeal
      carcinoma may not predict programmed death-1 blockade resistance.
AB  - The US FDA granted accelerated approval to pembrolizumab for microsatellite
      instability-high and mismatch repair deficient cancers. The response of
      programmed death-1 blockade in mismatch repair proficiency (pMMR) colorectal
      cancer is very poor, however, whether such treatment is effective in pMMR
      nasopharyngeal carcinoma (NPC) remains unknown. We report a case of a 51-year-old
      man with NPC. PET-CT scan revealed a space-occupying lesion in the left lung, and
      the pathologic result confirmed the occupying lesion originated from NPC.
      Meanwhile, both immunohistochemistry and PCR revealed that the occupying lesion
      belonged to pMMR NPC. The lung lesions largely shrunk after chemoradiotherapy.
      One year later, MRI showed brain occupancy, and brain lesion resection surgery
      was performed subsequently. The resected tissue was also validated to be the
      metastatic lesion from NPC. After one month, the patient was examined again by
      PET-CT, which showed multiple metastases in the liver, pelvis and adrenal gland.
      Since January 2017, the patient has been treated with pembrolizumab therapy.
      After five courses of treatment, both PET-CT and blood testing were repeated and
      demonstrated that metastases and serum Epstein-Barr virus DNA almost completely
      disappeared. We provide the first report that pembrolizumab has a confirmed
      objective response to microsatellite stability and pMMR NPC, and two biomarkers
      may not be sufficient to identify patients who might be resistant to such
      treatment in NPC.

PMID- 29348908
TI  - Correlation Clustering of Stable Angina Clinical Care Patterns for 506 Thousand
      Patients.
AB  - Objectives: Our goal was to apply statistical and network science techniques to
      depict how the clinical pathways of patients can be used to characterize the
      practices of care providers. Methods: We included the data of 506,087 patients
      who underwent procedures related to ischemic heart disease. Patients were
      assigned to one of the 136 primary health-care centers using a voting scheme
      based on their residence. The clinical pathways were classified, and the spectrum
      of the pathway types was computed for each center, then a network was built with
      the centers as nodes and spectrum correlations as edge weights. Then Louvain
      clustering was used to group centers with similar pathway spectra. Results: We
      identified 3 clusters with rather distinct characteristics that occupy quite
      compact spatial areas, though no geographical information was used in clustering.
      Network analysis and hierarchical clustering show the dominance of medical
      university clinics in each cluster. Conclusion: Though clinical guidelines
      provide a uniform regulation for medical decisions, doctors have great freedom in
      daily clinical practice. This freedom leads to regional preferences of certain
      clinical pathways, the intercenter professional links, and geographical locality
      and coupled with quantifiable consequences in terms of care costs and
      periprocedural risk of patients.

PMID- 29348909
TI  - Functionalized cationic [4]helicenes with unique tuning of absorption,
      fluorescence and chiroptical properties up to the far-red range.
AB  - Unprecedented regioselective post-functionalization of racemic and enantiopure
      cationic diaza [4]helicenes is afforded. The peripheral auxochrome substituents
      allow a general tuning of the electrochemical, photophysical and chiroptical
      properties of the helical dyes (26 examples). For instance, electronic absorption
      and circular dichroism are modulated from the orange to near-infrared spectral
      range (575-750 nm), fluorescence quantum efficiency is enhanced up to 0.55 (631
      nm) and circularly polarized luminescence is recorded in the red (|glum| ~ 10-3).

PMID- 29348910
TI  - Determinants of Colour Constancy and the Blue Bias.
AB  - We investigated several sensory and cognitive determinants of colour constancy
      across 40 illumination hues. In the first experiment, we measured colour naming
      for the illumination and for the colour induced by the illumination on the
      colorimetric grey. Results confirmed that the induced colours are approximately
      complementary to the colour of the illumination. In the second experiment, we
      measured colour constancy using achromatic adjustments. Average colour constancy
      was perfect under the blue daylight illumination and decreased in colour
      directions away from the blue daylight illumination due to undershooting and a
      strong blue bias. Apart from this blue bias, colour constancy was not related to
      illumination discrimination and to chromatic detection measured previously with
      the same setup and stimuli. We also observed a strong negative relationship
      between the degree of colour constancy and the consensus of naming the
      illumination colour. Constancy coincided with a low naming consensus, in
      particular because bluish illumination colours were sometimes seen as achromatic.
      Blue bias and category consensus alone explained >68%, and all determinants
      together explained >94% of the variance of achromatic adjustments. These findings
      suggest that colour constancy is optimised for blue daylight.

PMID- 29348911
TI  - Reduction of Flicker in Four-Stroke Motion of Color Images.
AB  - When two sequential video frames extracted from a single video clip are followed
      by the negative of the two frames, a viewer often experiences a visual illusion
      whereby a scene in the frames continuously moves in a single direction (four
      stroke apparent motion). To create a four-stroke apparent motion display, the
      image intensities of the whole of the second pair of images are reversed.
      However, this intensity reversal creates a strong impression of flicker that can
      be undesirable for comfortable viewing. This study reports that four-stroke
      apparent motion can be induced by only reversing the luminance intensities in
      those spatial areas which contain motion signals in high-pass filtered images.
      This use of only a partial reversal of image intensities greatly reduces the
      apparent flicker in the display while retaining motion perception.

PMID- 29348913
TI  - Complications during removal of stainless steel versus titanium nails used for
      intramedullary nailing of diaphyseal fractures of the tibia.
AB  - Objectives: Intramedullary nailing is the treatment of choice for fractures of
      the tibial shaft, which might necessitate the nail removal due to complications
      in the long-term. Although considered as a low-risk procedure, intramedullary
      nail removal is also associated with certain complications. Here, we compared the
      most commonly used stainless steel and titanium nails with respect to the
      complications during removal and clinical outcome for intramedullary nailing of
      diaphyseal fractures of the tibia. Patients and methods: Sixty-two patients (26
      females, 36 males) were included in this retrospective study. Of the removed
      nails, 24 were of stainless steel and 38 of titanium. Preoperative and
      intraoperative parameters, such as implant discomfort, anterior knee pain,
      operating time and amount of bleeding, and postoperative outcomes were evaluated
      for each patient. Results: Titanium nail group had more, but not statistically
      significant, intraoperative complications than stainless steel group during the
      removal of nails (p = .4498). Operating time and amount of intraoperative
      bleeding were significantly higher in titanium group than stainless steel group
      (p = .0306 and p < .001, respectively). Preoperative SF-36 physical component and
      KSS scores were significantly lower in patients who had removal of titanium nails
      than those of stainless steel nails, whereas there was no difference in terms of
      postoperative SF-36 and KSS scores. Conclusion: In conclusion, although greater
      bone contact with titanium increases implant stability, nail removal is more
      difficult, resulting in more longer surgical operation and more intraoperative
      bleeding. Therefore, we do not recommend titanium nail removal in asymptomatic
      patients.

PMID- 29348912
TI  - Genomic and molecular control of cell type and cell type conversions.
AB  - Organisms are made of a limited number of cell types that combine to form higher
      order tissues and organs. Cell types have traditionally been defined by their
      morphologies or biological activity, yet the underlying molecular controls of
      cell type remain unclear. The onset of single cell technologies, and more
      recently genomics (particularly single cell genomics), has substantially
      increased the understanding of the concept of cell type, but has also increased
      the complexity of this understanding. These new technologies have added a new
      genome wide molecular dimension to the description of cell type, with genome-wide
      expression and epigenetic data acting as a cell type 'fingerprint' to describe
      the cell state. Using these genomic fingerprints cell types are being
      increasingly defined based on specific genomic and molecular criteria, without
      necessarily a distinct biological function. In this review, we will discuss the
      molecular definitions of cell types and cell type control, and particularly how
      endogenous and exogenous transcription factors can control cell types and cell
      type conversions.

PMID- 29348914
TI  - Exploring health insurance services in Sudan from the perspectives of insurers.
AB  - Background: It has been 20 years since the introduction of health insurance in
      Sudan. This study was the first one that explored health insurance services in
      Sudan from the perspectives of the insurers. Methods: This was a qualitative,
      exploratory, interview study. The sampling frame was the list of Social Health
      Insurance and Private Health Insurance institutions in Sudan. Participants were
      selected from the four Social Health Insurance institutions and from five Private
      Health Insurance companies. The study was conducted in January and February 2017.
      In-depth individual interviews were conducted with a convenient sample of key
      executives from the different health insurers. Ideas and themes were identified
      and analysed using thematic analysis. Results: The result showed that universal
      coverage was not achieved despite long time presence of Social Health Insurance
      and Private Health Insurance in Sudan. All participants described their services
      as comprehensive. All participants have good perception of the quality of the
      services they provide, although none of them investigated customer satisfaction.
      The main challenges facing Social Health Insurance are achieving universal
      coverage, ensuring sustainability and recruitment of the informal sector and self
      employed population. Consumers' affordability of the premiums is the main
      obstacle for Private Health Insurance, while rising healthcare cost due to
      economic inflation is a challenge facing both Social Health Insurance and Private
      Health Insurance. Conclusion: In spite of the presence of Social Health Insurance
      and Private Health Insurance in Sudan, the country is still far from achieving
      universal coverage. Moreover, the sustainability of health insurance is
      questionable. The main reasons include low governmental financial resources and
      lack of affordability by beneficiaries especially for Private Health Insurance.
      This necessitates finding solutions to improve them or trying other types of
      health insurance. The quality of services provided by Social Health Insurance and
      Private Health Insurance was described as good, but no insurance in Sudan
      measured customer satisfaction as yet.

PMID- 29348915
TI  - Extended posterior approach for huge popliteal aneurysm extended to superficial
      femoral artery.
AB  - Objectives: Generally, popliteal artery aneurysms have been addressed surgically
      by a medial, posterior, or lateral approach. We have designed a new posterior
      approach that exposes the superficial femoral artery and entire popliteal artery
      without dividing any muscles in a just prone position. Methods and results: A 72
      year old man with huge popliteal aneurysm extended to superficial femoral artery
      was admitted to our hospital. Surgery was performed due to a high risk of
      rupture. An S-shaped skin incision was made in the popliteal fossa. We could not
      expose the proximal side of the giant aneurysm proximal to the foramen of the
      adductor magnus. We extended the skin incision to the proximal and exfoliated the
      medial side of semitendinosus muscle. We could expose the superficial femoral
      artery in this approach like in a medial approach. We could perform the
      interposition of great saphenous vein. Conclusion: The advantages of this
      approach allowed for entire exposure of the popliteal aneurysm in the same
      patient's position when we perform aneurysmectomy and bypass. It is possible for
      this approach to provide easy access to the superficial femoral artery proximal
      to the adductor hiatus and distal below-knee popliteal artery including the
      tibioperoneal trunk.

PMID- 29348916
TI  - An intravascular papillary endothelial hyperplasia of the hand radiologically
      mimicking a hemangiopericytoma: A case report and literature review.
AB  - Intravascular papillary endothelial hyperplasia is a rare benign vascular lesion
      of the skin and subcutaneous tissues, characterized by a reactive proliferation
      of endothelial cells that can present de novo in normal blood vessels (primary
      intravascular papillary endothelial hyperplasia), but it can also develop from a
      pre-existing vascular process (type II intravascular papillary endothelial
      hyperplasia), or it can arise in an extravascular location from a post-traumatic
      haematoma. The differential diagnosis between intravascular papillary endothelial
      hyperplasia and malignant vascular tumours can be challenging, due to the lacking
      of a specific radiologic description. We present a case of intravascular
      papillary endothelial hyperplasia of the hand radiologically mimicking a
      hemangiopericytoma.

PMID- 29348917
TI  - Refractory actinomycosis of the humerus.
AB  - Actinomycosis is a chronic, opportunistic infection caused by Actinomyces
      species, such as Actinomyces bacillus. Actinomycosis in long bones is very rare.
      To the best of our knowledge, isolated primary actinomycosis of the humerus is
      rarely reported in literature. We present a rare case of a refractory primary
      actinomycosis of the humerus. A 66-year-old man with no history of concomitant
      conditions was admitted to our hospital with a history of a tumour on the distal
      third of the left arm as a result of a closed trauma without fracture 20 years
      before. Pathological anatomy samples showed the presence of Actinomyces. Cultures
      were subjected to a prolonged incubation of 21 days under aerobic and anaerobic
      conditions and were always negative. He underwent several surgical procedures and
      received long-term antibiotic therapy with poor outcome. Primary actinomycosis in
      long bones is uncommon. Diagnosis may be challenging: considering the small
      number of case studies reported in the literature, symptoms are not specific, and
      the organism is difficult to isolate. Antibiotic treatment may not be sufficient
      to improve the clinical condition, and surgical alternatives should be
      considered.

PMID- 29348918
TI  - Safety and timing of resuming dabigatran after major gastrointestinal bleeding
      reversed by idarucizumab.
AB  - The recent introduction of direct oral anticoagulants, including rivaroxaban,
      dabigatran, apixaban, and edoxaban, for the acute treatment and secondary
      prevention of venous thromboembolism and in atrial fibrillation has been shown to
      provide greater clinical benefit than oral vitamin K antagonists. However, direct
      oral anticoagulants are associated with adverse events, the most common being
      major bleeding; such events require the reversal of the anticoagulant effects by
      specific agents. In this case report, we describe an 87-year-old female with
      atrial fibrillation treated with dabigatran who had massive rectal bleeding.
      Idarucizumab 5 g (2 * 2.5 g/50 mL) was successfully used to reverse dabigatran
      effect; subsequent to this, treatment with dabigatran was resumed, and there were
      no further bleeding events. This suggests that dabigatran can be safely restarted
      after major bleeding, but this outcome needs to be confirmed in studies involving
      larger groups of patients.

PMID- 29348919
TI  - Thoracic stent graft placement for repair of iatrogenic aortic injury secondary
      to sheath placement during pacemaker insertion.
AB  - We describe the inadvertent cannulation of the proximal descending thoracic
      aortic stent with a five French sheath during attempted pacemaker placement in an
      88- year-old male. The injury was managed successfully by the percutaneous
      placement of a thoracic aortic stent graft with good outcome. Our case highlights
      the feasibility of managing this uncommon injury with this technique.

PMID- 29348920
TI  - Wiskott-Aldrich syndrome that was initially diagnosed as immune thrombocytopenic
      purpura secondary to a cytomegalovirus infection.
AB  - Wiskott-Aldrich syndrome is a rare X-linked recessive disease resulting from
      variations in the WAS gene. Wiskott-Aldrich syndrome is sometimes difficult to
      differentiate from immune thrombocytopenic purpura. A 2-month-old boy was
      admitted to our hospital for purpura and thrombocytopenia. His mean platelet
      volume was reported to be normal. Treatment with intravenous immunoglobulins
      failed to improve the patient's platelet count. Subsequently, an acute
      cytomegalovirus infection was confirmed by serological testing and antigenemia.
      The patient was diagnosed with immune thrombocytopenic purpura secondary to a
      cytomegalovirus infection. However, based on the patient's clinical course and
      the refractoriness of his condition, Wiskott-Aldrich syndrome was strongly
      suspected. Through direct sequencing of the genomic DNA of the Wiskott-Aldrich
      syndrome protein (WASP) gene, we identified a novel missense mutation in exon 3
      of the patient's WASP gene (c. 343 C>T, p. H115T), and the patient was diagnosed
      with Wiskott-Aldrich syndrome at 3 months after onset. Children with Wiskott
      Aldrich syndrome are often initially diagnosed with immune thrombocytopenic
      purpura, which can lead to inappropriate treatment and delays to life-saving
      definitive therapy. Our findings imply that Wiskott-Aldrich syndrome should be
      considered as a differential diagnosis in cases of refractory immune
      thrombocytopenic purpura combined with a cytomegalovirus infection.

PMID- 29348921
TI  - Genetic characteristics of VanA-type vancomycin-resistant Enterococcus faecalis
      and Enterococcus faecium in Cuba.
AB  - VanA-type vancomycin-resistant enterococci isolates from bloodstream infections
      in Cuba were genetically characterized. Enterococcus faecalis isolates were
      assigned to sequence type (ST) 28, closely related to Eastern Europe, while
      Enterococcus faecium belonged to ST262, ST656 and ST1349, and showed different
      genetic profiles.

PMID- 29348922
TI  - Taxonogenomic description of four new Clostridium species isolated from human
      gut: 'Clostridium amazonitimonense', 'Clostridium merdae', 'Clostridium
      massilidielmoense' and 'Clostridium nigeriense'.
AB  - Culturomics investigates microbial diversity of the human microbiome by combining
      diversified culture conditions, matrix-assisted laser desorption/ionization time
      of-flight mass spectrometry and 16S rRNA gene identification. The present study
      allowed identification of four putative new Clostridium sensu stricto species:
      'Clostridium amazonitimonense' strain LF2T, 'Clostridium massilidielmoense'
      strain MT26T, 'Clostridium nigeriense' strain Marseille-P2414T and 'Clostridium
      merdae' strain Marseille-P2953T, which we describe using the concept of
      taxonogenomics. We describe the main characteristics of each bacterium and
      present their complete genome sequence and annotation.

PMID- 29348923
TI  - Cervicofacial lymphadenitis due to Mycobacterium mantenii: rapid and reliable
      identification by MALDI-TOF MS.

PMID- 29348924
TI  - Mortality and Hospitalizations in Intensive Dialysis: A Systematic Review and
      Meta-Analysis.
AB  - Background: Survival and hospitalization are critically important outcomes
      considered when choosing between intensive hemodialysis (HD), conventional HD,
      and peritoneal dialysis (PD). However, the comparative effectiveness of these
      modalities is unclear. Objective: We had the following aims: (1) to compare the
      association of mortality and hospitalization in patients undergoing intensive HD,
      compared with conventional HD or PD and (2) to appraise the methodological
      quality of the supporting evidence. Data Sources: MEDLINE, Embase, ISI Web of
      Science, CENTRAL, and nephrology conference abstracts. Study Eligibility
      Participants and Interventions: We included cohort studies with comparator arm,
      and randomized controlled trials (RCTs) with >50% of adult patients (>=18 years)
      comparing any form of intensive HD (>4 sessions/wk or >5.5 h/session) with any
      form of chronic dialysis (PD, HD <=4 sessions/wk or <=5.5 h/session), that
      reported at least 1 predefined outcome (mortality or hospitalization). Methods:
      We used the GRADE approach to systematic reviews and quality appraisal. Two
      reviewers screened citations and full-text articles, and extracted study-level
      data independently, with discrepancies resolved by consensus. We pooled effect
      estimates of randomized and observational studies separately using generic
      inverse variance with random effects models, and used fixed-effects models when
      only 2 studies were available for pooling. Predefined subgroups for the intensive
      HD cohorts were classified by nocturnal versus short daily HD and home versus in
      center HD. Results: Twenty-three studies with a total of 70 506 patients were
      included. Of the observational studies, compared with PD, intensive HD had a
      significantly lower mortality risk (hazard ratio [HR]: 0.67; 95% confidence
      interval [CI]: 0.53-0.84; I2 = 91%). Compared with conventional HD, home
      nocturnal (HR: 0.46; 95% CI: 0.38-0.55; I2 = 0%), in-center nocturnal (HR: 0.73;
      95% CI: 0.60-0.90; I2 = 57%) and home short daily (HR: 0.54; 95% CI: 0.31-0.95;
      I2 = 82%) intensive regimens had lower mortality. Of the 2 RCTs assessing
      mortality, in-center short daily HD had lower mortality (HR: 0.54; 95% CI: 0.31
      0.93), while home nocturnal HD had higher mortality (HR: 3.88; 95% CI: 1.27
      11.79) in long-term observational follow-up. Hospitalization days per patient
      year (mean difference: -1.98; 95% CI: -2.37 to -1.59; I2 = 6%) were lower in
      nocturnal compared with conventional HD. Quality of evidence was similarly low or
      very low in RCTs (due to imprecision) and observational studies (due to residual
      confounding and selection bias). Limitations: The overall quality of evidence was
      low or very low for critical outcomes. Outcomes such as quality of life,
      transplantation, and vascular access outcomes were not included in our review.
      Conclusions: Intensive HD regimens may be associated with reduced mortality and
      hospitalization compared with conventional HD or PD. As the quality of supporting
      evidence is low, patients who place a high value on survival must be adequately
      advised and counseled of risks and benefits when choosing intensive dialysis.
      Practice guidelines that promote shared decision-making are likely to be helpful.

PMID- 29348925
TI  - Volume Estimates in Chronic Hemodialysis Patients by the Watson Equation and
      Bioimpedance Spectroscopy and the Impact on the Kt/Vurea calculation.
AB  - Background: Accurate assessment of total body water (TBW) is essential for the
      evaluation of dialysis adequacy (Kt/Vurea). The Watson formula, which is
      recommended for the calculation of TBW, was derived in healthy volunteers thereby
      leading to potentially inaccurate TBW estimates in maintenance hemodialysis
      recipients. Bioimpedance spectroscopy (BIS) may be a robust alternative for the
      measurement of TBW in hemodialysis recipients. Objectives: The primary objective
      of this study was to evaluate the accuracy of Watson formula-derived TBW
      estimates as compared with TBW measured with BIS. Second, we aimed to identify
      the anthropometric characteristics that are most likely to generate inaccuracy
      when using the Watson formula to calculate TBW. Finally, we derived novel
      anthropometric equations for the more accurate estimation of TBW. Design and
      Setting: This was a cross-sectional study of prevalent in-center HD patients at
      St Michael's Hospital. Patients: One hundred eighty-four hemodialysis patients
      (109 men and 75 women) were evaluated in this study. Measurements: Anthropometric
      measurements including weight, height, waist circumference, midarm circumference,
      and 4-site skinfold (biceps, triceps, subscapular, and suprailiac) thickness were
      measured; fat mass was measured using the formula by Durnin and Womersley. We
      measured TBW by BIS using the Body Composition Monitor (Fresenius Medical Care,
      Bad Homburg, Germany). Methods: We used the Bland-Altman method to calculate the
      difference between the TBW derived from the Watson method and the BIS. To derive
      new equations for TBW estimation, Pearson's correlation coefficients between BIS
      TBW (the reference test) and other variables were examined. We used the least
      squares regression analysis to develop parsimonious equations to predict TBW.
      Results: TBW values based on the Watson method had a high correlation with BIS
      TBW (correlation coefficients = 0.87 and P < .001). Despite the high correlation,
      the Watson formula overestimated TBW by 5.1 (4.5-5.8) liters and 3.8 (3.0-4.5)
      liters, in men and women, respectively. Higher fat mass and waist circumference
      (general and abdominal obesity) were correlated with the greater TBW
      overestimation by the Watson formula. We created separate equations for men and
      women based on weight and waist circumference. Limitations: The main limitation
      of our study was the lack of an external validation for our novel estimating
      equation. Furthermore, though BIS has been validated against traditional
      reference standards, our assumption that it represents the "gold standard" for
      body compartment assessment may be flawed. Conclusions: The Watson formula
      generally overestimates TBW in chronic dialysis recipients, particularly in
      patients with the highest waist circumference. Widespread reliance on the Watson
      formula for derivation of TBW may lead to the underestimation of Kt/Vurea..

PMID- 29348926
TI  - A double-blind, placebo-controlled, single ascending-dose study of remyelinating
      antibody rHIgM22 in people with multiple sclerosis.
AB  - Objective: The objective of this paper is to assess, in individuals with
      clinically stable multiple sclerosis (MS), the safety, tolerability,
      pharmacokinetics (PK) and exploratory pharmacodynamics of the monoclonal
      recombinant human antibody IgM22 (rHIgM22). Methods: Seventy-two adults with
      stable MS were enrolled in a double-blind, randomized, placebo-controlled, single
      ascending-dose, Phase 1 trial examining rHIgM22 from 0.025 to 2.0 mg/kg.
      Assessments included MRI, MR spectroscopy, plasma PK, and changes in clinical
      status, laboratory values and adverse events for three months. The final cohort
      had additional clinical, ophthalmologic, CSF collection and exploratory biomarker
      evaluations. Participants were monitored for six months. Results: rHIgM22 was
      well tolerated with no clinically significant safety signals. Noncompartmental PK
      modeling demonstrated linear dose-proportionality both of Cmax and AUC0-Last. The
      steady-state apparent volume of distribution of approximately 58 ml/kg suggested
      primarily vascular compartmentalization. CSF:plasma rHIgM22 concentration
      increased from 0.003% on Day 2 for both 1.0 and 2.0 mg/kg to 0.056% and 0.586%
      for 1.0 and 2.0 mg/kg, respectively, on Day 29. No statistically significant
      treatment-related changes were observed in exploratory pharmacodynamic outcome
      measures included for the 21 participants of the extension cohort. Conclusions:
      Single doses of rHIgM22 were well tolerated and exhibited linear PK, and antibody
      was detected in the CSF.

PMID- 29348927
TI  - Improved cognitive performance and event-related potential changes following
      working memory training in patients with multiple sclerosis.
AB  - Background: Few studies of cognitive rehabilitation in multiple sclerosis (MS)
      have targeted working memory specifically. Objective: We examined the effects of
      n-back working memory training on cognitive performance and brain function in
      patients with MS. Methods: Patients with MS (n = 12) and healthy controls (HC; n
      = 12) underwent 20 sessions of n-back working memory training. Before and after
      training (pre- and posttest) cognitive event-related potential (ERP) measures
      were obtained during a 3-back task. In addition, a battery of cognitive tests was
      administered. Results: Following n-back training, both MS patients and HCs showed
      significant improvement on tests of working memory, processing speed, complex
      attention, and reasoning ability. MS and HCs also exhibited an enhancement of N2
      ERP component amplitude, and earlier N2 and P3 latencies, following n-back
      training. Conclusions: Targeted training of working memory with the n-back task
      may improve cognitive function in MS. Enhancement of N2 ERP component amplitude
      and shorter N2 and P3 latency following training in patients with MS is
      consistent with plasticity of neural processes that are involved in working
      memory.

PMID- 29348928
TI  - Glaucomatocyclitic Crises May Occur in Patients with Narrow or Closed Angles.
AB  - Purpose: To report cases of glaucomatocyclitic crises and discuss the possibility
      of occurrence in patients with narrow or closed angles. Background: The
      prevalence of angle closure is much higher among Asians than among the Western
      population. Currently, there is no evidence for a direct relationship between the
      etiology and angle structure. Design: A retrospective and observational case
      series. Methods: We retrospectively collected data from nine adult patients
      (three males and six females) who were diagnosed with a glaucomatocyclitic crisis
      and a shallow anterior chamber over a 21-year period, from 1995 to 2016, at the
      Kaohsiung Medical University Hospital. A narrow angle was defined as a grade less
      than the Shaffer system grade II. Ophthalmic examinations, including anterior
      segment biomicroscopy, direct ophthalmoscopy, intraocular pressure measurements,
      anterior chamber reaction, visual field tests, and the grade of the anterior
      chamber angle according to the Shaffer system, were reviewed. Results: These
      patients experienced at least one typical unilateral ocular hypertensive episode
      that fulfilled the criteria of a glaucomatocyclitic crisis without the angle
      feature. All patients had gonioscopically narrow or closed angles with or without
      peripheral anterior synechiae. Conclusions: The coexistence of narrow or closed
      angles and a glaucomatocyclitic crisis is possible, especially in patients of
      Asian descent. In patients with shallow anterior chambers, a glaucomatocyclitic
      crisis may be a cause of acute glaucoma episodes.

PMID- 29348929
TI  - The Influence of Environmental Factors on the Prevalence of Myopia in Poland.
AB  - Purpose: In the paper, we describe and discuss the results of epidemiological
      studies concerning myopia carried out in Poland. Materials and Methods: Results
      from the examination of 5601 Polish school children and students (2688 boys and
      2913 girls) aged 6 to 18 years were analyzed. The mean age was 11.9 +/- 3.2
      years. Every examined student had undergone the following examinations: distance
      visual acuity testing, cover test, anterior segment evaluation, and cycloplegic
      retinoscopy after instillation of 1% tropicamide, and a questionnaire was taken.
      Results: We have found that (1) intensive near work (writing, reading, and
      working on a computer) leads to a higher prevalence of myopia, (2) watching
      television does not influence the prevalence of myopia, and (3) being outdoors
      decreases the prevalence of myopia. Conclusions: The results of our study point
      to insufficiency of accommodation contributing to the pathogenesis of myopia.

PMID- 29348930
TI  - Analysis of Genetic Mutations in a Cohort of Hereditary Optic Neuropathy in
      Shanghai, China.
AB  - Purpose: To evaluate the clinical classification and characteristics of
      hereditary optic neuropathy patients in a single center in China. Method:
      Retrospective case study. Patients diagnosed with hereditary optic neuropathy
      between January 2014 and December 2015 in the neuro-ophthalmology division in
      Shanghai Eye and ENT Hospital of Fudan University were recruited. Clinical
      features as well as visual field, brain/orbital MRI, and spectrum domain optical
      coherence tomography (SD-OCT) were analyzed. Results: Eighty-two patients
      diagnosed by gene test were evaluated, including 66 males and 16 females. The
      mean age of the patients was 19.4 years (range, 5-46 years). A total of 158 eyes
      were analyzed, including 6 unilateral, 61 bilateral, and 15 sequential. The
      median duration of the disease was 0.5 year (range, 0.1-20 years). Genetic test
      identified 68 patients with Leber hereditary optic neuropathy, 9 with dominant
      optic neuropathy, and 2 with a Wolfram gene mutation. There was also one case of
      hereditary spastic paraplegia, spinocerebellar ataxia, and polymicrogyria with
      optic nerve atrophy, respectively. Conclusion: Leber hereditary optic neuropathy
      is the most common detected type of hereditary optic neuropathy in Shanghai,
      China. The detection of other autosomal mutations in hereditary optic neuropathy
      is limited by the currently available technique.

PMID- 29348931
TI  - Detection of Silent Type I Choroidal Neovascular Membrane in Chronic Central
      Serous Chorioretinopathy Using En Face Swept-Source Optical Coherence Tomography
      Angiography.
AB  - Purpose: To evaluate the efficacy of SS-OCTA in the detection of silent CNV
      secondary to chronic CSCR compared to that of FFA and SS-OCT. Patients and
      Methods: A retrospective observational case series reviewing the clinical data,
      FFA, SS-OCT, and SS-OCTA images of patients with chronic CSCR, and comparing the
      findings. SS-OCTA detects the CNV complex and delineates it from the surrounding
      pathological features of chronic CSCR by utilizing the blood flow detection
      algorithm, OCTARA, and the ultrahigh-definition B-scan images of the retinal
      microstructure generated by swept-source technology. The bivariate correlation
      procedure was used for the calculation of the correlation matrix of the variables
      tested. Results: The study included 60 eyes of 40 patients. Mean age was 47.6
      years. Mean disease duration was 14.5 months. SS-OCTA detected type 1 CNV in 5
      eyes (8.3%). In all 5 eyes, FFA and SS-OCT were inconclusive for CNV. The
      presence of foveal thinning, opaque material beneath irregular flat PED, and
      increased choroidal thickness in chronic CSCR constitutes a high-risk profile for
      progression to CNV development. Conclusion: Silent type 1 CNV is an established
      complication of chronic CSCR. SS-OCTA is indispensable in excluding CNV
      especially in high-risk patients and whenever FFA and SS-OCT are inconclusive.

PMID- 29348932
TI  - Long-Term Follow-Up in Children with Anisocoria: Cocaine Test Results and Patient
      Outcome.
AB  - Background: Evaluation of anisocoria including pharmacological testing for
      Horner's syndrome in the pediatric population is challenging in view of potential
      serious underlying disease. We describe cocaine test results, outcome of systemic
      investigation, and long-term follow-up in children with anisocoria. Methods:
      Retrospective review of medical records and phone interview of consecutive
      pediatric patients (<18 years old) who underwent cocaine testing from August 2007
      to July 2015 at a tertiary referral centre. Results: A total of 35 patients were
      included with a positive, negative, or inconclusive cocaine test in 12/35, 19/35,
      and 4/35, respectively. Systemic investigation was performed in 11 of the
      patients with a positive and in 2 of the patients with an inconclusive cocaine
      test result. Mediastinal Hodgkin lymphoma was found in one patient with an
      inconclusive cocaine test result. Two other cases were presumably related to
      birth trauma and surgical trauma. None of the other children further developed
      any pathology during the follow-up period of 34.8 months (range 0-106.6).
      Conclusions: In most children with anisocoria and a positive cocaine test result,
      systemic investigation did not reveal any underlying etiology. The only malignant
      disease was diagnosed in a patient with a suspicion of Horner's syndrome but with
      an inconclusive cocaine test result in our cohort.

PMID- 29348933
TI  - Prevalence and Associated Risk Factors of Hypertension: A Cross-Sectional Study
      in Urban Varanasi.
AB  - Hypertension is a major public health problem and important area of research due
      to its high prevalence and being major risk factor for cardiovascular diseases
      and other complications. Objectives. (1) To assess the prevalence of hypertension
      and its associated factors and (2) to estimate awareness, treatment, and adequacy
      of control of hypertension among study subjects. Methods and Materials. A
      community based cross-sectional study with multistage sampling design was
      conducted among urban population of Varanasi. A modified WHO STEPS interview
      schedule on 640 study subjects aged 25-64 years was used. Results. The prevalence
      of hypertension was 32.9% (male: 40.9%, female: 26.0%). Mean systolic and
      diastolic BP were 124.25 +/- 15.05 mmHg and 83.45 +/- 9.49 mmHg, respectively.
      Higher odds of being hypertensive were found in male subjects, eldest age group,
      married subjects, subjects of upper socioeconomic status, illiterate subjects,
      and retired subjects. Tobacco and alcohol consumption, overweight, obesity, and
      abdominal obesity were also associated with hypertension. Out of the total
      hypertensive 211 subjects, only 81 (38.4%) were aware about their hypertension
      status; out of those, 57 (70.4%) were seeking treatment and 20 (35.08%) had their
      blood pressure adequately controlled. Conclusion. Around one-third of the
      subjects were hypertensive and half of the study subjects were prehypertensive in
      this area. The awareness, treatment, and control of high blood pressure were also
      very low.

PMID- 29348934
TI  - "In Silico" Characterization of 3-Phytase A and 3-Phytase B from Aspergillus
      niger.
AB  - Phytases are used for feeding monogastric animals, because they hydrolyze phytic
      acid generating inorganic phosphate. Aspergillus niger 3-phytase A (PDB: 3K4Q)
      and 3-phytase B (PDB: 1QFX) were characterized using bioinformatic tools. Results
      showed that both enzymes have highly conserved catalytic pockets, supporting
      their classification as histidine acid phosphatases. 2D structures consist of 43%
      alpha-helix, 12% beta-sheet, and 45% others and 38% alpha-helix, 12% beta-sheet,
      and 50% others, respectively, and pI 4.94 and 4.60, aliphatic index 72.25 and
      70.26 and average hydrophobicity of -0,304 and -0.330, respectively, suggesting
      aqueous media interaction. Glycosylation and glycation sites allowed detecting
      zones that can affect folding and biological activity, suggesting fragmentation.
      Docking showed that H59 and H63 act as nucleophiles and that D339 and D319 are
      proton donor residues. MW of 3K4Q (48.84 kDa) and 1QFX (50.78 kDa) is similar;
      1QFX forms homodimers which will originate homotetramers with several catalytic
      center accessible to the ligand. 3K4Q is less stable (instability index 45.41)
      than 1QFX (instability index 33.66), but the estimated lifespan for 3K4Q is
      superior. Van der Waals interactions generate hydrogen bonds between the active
      center and O2 or H of the phytic acid phosphate groups, providing greater
      stability to these temporal molecular interactions.

PMID- 29348935
TI  - Effect of Male Involvement on the Nutritional Status of Children Less Than 5
      Years: A Cross Sectional Study in a Rural Southwestern District of Uganda.
AB  - Background: Undernutrition among children less than 5 years is still a public
      health concern in most developing countries. Fathers play a critical role in
      providing support in improving maternal and child health. There is little studied
      on male involvement and its measurement in child nutrition; therefore, this paper
      explores the level of male involvement in child feeding and its association with
      the nutritional status of the children less than 5 years of age. Methods: A cross
      sectional study among 346 households, 3 focus group discussions, and 4 key
      informant interviews were conducted in one rural district in Uganda. Adjusted
      odds ratios (aORs) and 95% confidence intervals (95% CI) of associated factors
      were estimated and focus group discussions and in-depth interviews were conducted
      and summarized into themes. Results: The study revealed the highest percentage of
      the males provided money to buy food for the children (93.6%), and only 9.8% have
      ever accompanied mothers to young child clinics. Conclusion: In this study, most
      males were involved in buying food for their children, and providing money for
      transport to young child clinics was associated with normal nutritional status of
      children less than 5 years in the study area.

PMID- 29348936
TI  - Guiding Inspiratory Flow: Development of the In-Check DIAL G16, a Tool for
      Improving Inhaler Technique.
AB  - Portable inhalers are divisible into those that deliver medication by patient
      triggering (pMDIs: a gentle slow inhalation) and those that use the patient's
      inspiratory effort as the force for deaggregation and delivery (DPIs: a stronger
      deeper inspiratory effort). Patient confusion and poor technique are commonplace.
      The use of training tools has become standard practice, and unique amongst these
      is an inspiratory flow meter (In-Check) which is able to simulate the resistance
      characteristics of different inhalers and, thereby, guide the patient to the
      correct effort. In-Check's origins lie in the 1960s peak expiratory flow meters,
      the development of the Mini-Wright peak flow meter, and inspiratory flow
      assessment via the nose during the 1970s-1980s. The current device (In-Check DIAL
      G16) is the third iteration of the original 1998 training tool, with detailed and
      ongoing assessments of all common inhaler resistances (including combination and
      breath-actuated inhaler types) summarised into resistance ranges that are preset
      within the device. The device works by interpolating one of six ranges with the
      inspiratory effort. Use of the tool has been shown to be contributory to
      significant improvements in asthma care and control, and it is being advocated
      for assessment and training in irreversible lung disease.

PMID- 29348937
TI  - Work Change in Multiple Sclerosis as Motivated by the Pursuit of Illness-Work
      Life Balance: A Qualitative Study.
AB  - Individuals with multiple sclerosis have a tendency to make early decisions for
      work change, even in reversible, episodic, or mild disease stages. To better
      understand how a multiple sclerosis (MS) diagnosis influences perceptions of work
      and motivations for work changes, we conducted a hermeneutic phenomenology study
      to explore the work lives of ten individuals with MS in Malaysia. The
      interpretive analysis and cumulative narratives depict an overarching change in
      their concept of ideal work and life aspirations and how participants make
      preemptive work changes to manage illness-work-life futures in subjectively
      meaningful ways. Discussions on their integrated pursuit of finding dynamic and
      subjective illness-work-life balance include reconciling the problem of hard work
      and stress on disease activity and progress, making positive lifestyle changes as
      health management behaviour, and the motivational influence of their own life and
      family roles: the consideration of their spouses, parents, and children. At an
      action level, work change was seen as moral and necessary for the management of
      illness futures. Our findings contribute insights on how individual perceptions
      and holistic life management decisions contribute to on-going and disrupted work
      trajectories, which can inform practice and policy on early interventions to
      support continued employment.

PMID- 29348938
TI  - Treatment of Anemia of Chronic Disease with True Iron Deficiency in Pregnancy.
AB  - Objective: We assess and compare the efficacy of anemia treatment in pregnant
      women with anemia of chronic disease with true iron deficiency and in women with
      iron deficiency anemia. Study Design: Fifty patients with moderate anemia
      (hemoglobin 8.0-9.9 g/dl) and iron deficiency (ferritin < 15 MUg/l) were treated
      in the Anemia Clinic at the Department of Obstetrics. Results: All patients
      showed stimulation of erythropoiesis as evidenced by an increase in reticulocyte
      count at day eight of therapy and showed an increase in hemoglobin and hematocrit
      at the end of therapy (p < 0.001). The target hemoglobin (>=10.5 g/dl) was
      achieved in 45/50 women (90%). 12 patients showed anemia of chronic disease with
      true iron deficiency (12/50; 24%). Seven women (7/12; 59%) with anemia of chronic
      disease and iron deficiency responded well to anemia treatment. 50% of women with
      anemia of chronic disease and iron deficiency (3/6) responded well to intravenous
      iron, and 67% (4/6) responded well to the combination of intravenous iron and
      recombinant human erythropoietin. Conclusion: Because of frequent true iron
      deficiency in pregnant women with anemia of chronic disease, anemia of chronic
      disease in pregnancy is often falsely diagnosed as iron deficiency anemia.

PMID- 29348939
TI  - Effect of Insoles with a Toe-Grip Bar on Toe Function and Standing Balance in
      Healthy Young Women: A Randomized Controlled Trial.
AB  - Objective: The aim of this randomized controlled study was to investigate the
      effects of insoles with a toe-grip bar on toe function and standing balance in
      healthy young women. Methods: Thirty female subjects were randomly assigned to an
      intervention group or a control group. The intervention group wore shoes with
      insoles with a toe-grip bar. The control group wore shoes with general insoles.
      Both groups wore the shoes for 4 weeks, 5 times per week, 9 hours per day. Toe
      grip strength, toe flexibility, static balance (total trajectory length and
      envelope area of the center of pressure), and dynamic balance (functional reach
      test) were measured before and after the intervention. Results: Significant
      interactions were observed for toe-grip strength and toe flexibility (F = 12.53,
      p < 0.01; F = 5.84, p < 0.05, resp.), with significant improvement in the
      intervention group compared with that in the control group. Post hoc comparisons
      revealed that both groups showed significant improvement in toe-grip strength (p
      < 0.01 and p < 0.05, resp.), with higher benefits observed for the intervention
      group (p < 0.01). Conversely, no significant interaction was observed in the
      total trajectory length, envelope area, and functional reach test. Conclusions:
      This study suggests that insoles with a toe-grip bar contribute to improvements
      in toe-grip strength and toe flexibility in healthy young women.

PMID- 29348940
TI  - Perceptions and Practices of the Iranian Population regarding Skin Cancers: A
      Literature Review.
AB  - Despite being preventable, more than 15% of all cancer cases in Iran occur in the
      skin, making them the most commonly diagnosed malignancy in the country. The
      purpose of this study is to gain an insight into the current skin cancer related
      knowledge, attitudes, beliefs, and practices among the Iranian population. A
      systematic computer based literature search was conducted using databases for
      articles published through April 2017. Research studies included those that
      measured skin cancer or sun protection related knowledge, attitudes, beliefs, and
      behaviors in different Iranian population groups. Exclusion criteria for the
      articles included (1) irrelevant topics to the review article's aim, (2) articles
      that focused on the treatment of skin cancers instead of prevention practices,
      and (3) similar studies conducted on populations not indigenous to Iran. A total
      of 25 articles that met the eligibility criteria were included in the review.
      Predominant data were collected via questionnaires. Skin cancer related knowledge
      varied from low to high across the studies. Moreover, there was a pattern of low
      perceived skin cancer susceptibility and severity. Overall, there was low usage
      of sun protection methods among the Iranian population. The findings of this
      study show that efforts to prevent skin cancer are needed. Education concerning
      the dangers of sun exposure as well as strategies used to prevent or lower the
      risk of developing skin cancer should be stressed.

PMID- 29348941
TI  - The Immunoexpression of Glucocorticoid Receptors in Breast Carcinomas,
      Lactational Change, and Normal Breast Epithelium and Its Possible Role in Mammary
      Carcinogenesis.
AB  - The role of estrogen and progesterone receptors in breast cancer biology is well
      established. In contrast, other steroid hormones are less well studied.
      Glucocorticoids (GCs) are known to play a role in mammary development and
      differentiation; thus, it is of interest to attempt to delineate their
      immunoexpression across a spectrum of mammary epithelia. Aim. To delineate the
      distribution pattern of glucocorticoid receptors (GRs) in malignant versus
      nonmalignant epithelium with particular emphasis on lactational epithelium.
      Materials and Methods. Immunohistochemistry (IHC) for GRs was performed on
      archival formalin-fixed paraffin-embedded tissue blocks of 96 cases comprising 52
      invasive carcinomas, 21 cases with lactational change, and 23 cases showing
      normal mammary tissue histology. Results. Results reveal an overexpression of GRs
      in mammary malignant epithelium as compared to both normal and lactational groups
      individually and combined. GR overexpression is significantly more pronounced in
      HER-2-negative cancers. Discussion. This is the first study to compare GR
      expression in human lactating epithelium versus malignant and normal epithelium.
      The article discusses the literature related to the pathobiology of GCs in the
      breast with special emphasis on breast cancer. Conclusion. The lactational
      epithelium did not show overexpression of GR, while GR was overexpressed in
      mammary NST (ductal) carcinoma, particularly HER-2-negative cancers.

PMID- 29348942
TI  - Molecular Signatures of Radiation Response in Breast Cancer: Towards Personalized
      Decision-Making in Radiation Treatment.
AB  - Recent advances in gene expression profiling have allowed for a more
      sophisticated understanding of the biology of breast cancers. These advances led
      to the development of molecular signatures that now allow clinicians to more
      individually tailor recommendations regarding the utility and necessity of
      systemic therapies for women with breast cancer. Indeed, these molecularly based
      tests have been incorporated into national and international best practice
      guidelines and are now part of routine practice. Similar, though slower, progress
      is being made in the development of molecular signatures predictive of radiation
      response and necessity for women with breast cancer. This article will discuss
      the history of radiation response signature development, the current state of
      these signatures under ongoing clinical development, the barriers to their
      clinical adoption, and upcoming changes and opportunities that may allow for the
      personalized radiation treatment recommendations enabled by the development of
      these signatures.

PMID- 29348943
TI  - Interhemispheric Pathways Are Important for Motor Outcome in Individuals with
      Chronic and Severe Upper Limb Impairment Post Stroke.
AB  - Background: Severity of arm impairment alone does not explain motor outcomes in
      people with severe impairment post stroke. Objective: Define the contribution of
      brain biomarkers to upper limb motor outcomes in people with severe arm
      impairment post stroke. Methods: Paretic arm impairment (Fugl-Meyer upper limb,
      FM-UL) and function (Wolf Motor Function Test rate, WMFT-rate) were measured in
      15 individuals with severe (FM-UL <= 30/66) and 14 with mild-moderate (FM-UL >
      40/66) impairment. Transcranial magnetic stimulation and diffusion weight imaging
      indexed structure and function of the corticospinal tract and corpus callosum.
      Separate models of the relationship between possible biomarkers and motor
      outcomes at a single chronic (>=6 months) time point post stroke were performed.
      Results: Age (DeltaR20.365, p = 0.017) and ipsilesional-transcallosal inhibition
      (DeltaR20.182, p = 0.048) explained a 54.7% (p = 0.009) variance in paretic WMFT
      rate. Prefrontal corpus callous fractional anisotropy (PF-CC FA) alone explained
      49.3% (p = 0.007) variance in FM-UL outcome. The same models did not explain
      significant variance in mild-moderate stroke. In the severe group, k-means
      cluster analysis of PF-CC FA distinguished two subgroups, separated by a
      clinically meaningful and significant difference in motor impairment (p = 0.049)
      and function (p = 0.006) outcomes. Conclusion: Corpus callosum function and
      structure were identified as possible biomarkers of motor outcome in people with
      chronic and severe arm impairment.

PMID- 29348945
TI  - The Use of Adenosine to Enable Safe Implantation of Transcatheter Tricuspid
      Valve.
AB  - High precision is necessary during percutaneous transcatheter heart valve
      implantation. The precision of the implantation has been established by
      increasing the heart rate (usually to 200 beats per minute) to the point of
      significantly reduced cardiac output and thus minimizing valve movement.
      Routinely, this tachycardia is induced by rapid pacing. Here we report a case of
      failure to pace during valve-in-valve (VIV) Edwards Sapien XT implantation in the
      tricuspid valve position. Transient cardiac arrest was induced by intravenous
      adenosine injection enabling accurate valve implantation.

PMID- 29348944
TI  - A Longitudinal fMRI Research on Neural Plasticity and Sensory Outcome of Carpal
      Tunnel Syndrome.
AB  - Peripheral nerve compression is reported to induce cortical plasticity, which was
      well pictured by former researches. However, the longitudinal changes brought by
      surgical treatment are not clear. In this research, 18 subjects who suffered from
      bilateral carpal tunnel syndrome were evaluated using task-dependent fMRI and
      electromyography assessment before and after surgery. The third digit was
      tactually simulated by von Frey filaments. The results demonstrated that the
      pattern of activation was similar but a decreased extent of activation in the
      postcentral gyrus, inferior frontal lobe, superior frontal lobe, and
      parahippocampal gyrus after surgery was found. The correlation analysis showed a
      significant correlation between the decreased number of activated voxels and the
      improvement of EMG performance. This result implied a potential connection
      between fMRI measurement and clinical improvement.

PMID- 29348946
TI  - Group A Streptococci-Associated Necrotizing Fasciitis following Cat Bite in an
      Immunocompromised Patient.
AB  - Necrotizing soft tissue infections are characterized clinically by fulminant
      tissue destruction, systemic signs of toxicity, and high mortality. Accurate
      diagnosis and appropriate treatment must include early surgical intervention and
      antibiotic therapy. Mortality rate is very high and could be even higher in an
      immunocompromised host. We present a 57-year-old female with history of
      rheumatoid arthritis on oral corticosteroid and methotrexate therapy with painful
      swelling of the left hand following a cat bite that was diagnosed as having group
      A streptococcus pyogenes-associated necrotizing fasciitis. Treatment with
      ampicillin-sulbactam, Clindamycin, and surgical debridement was performed. In
      spite of all the adequate therapy she succumbed to death from streptococcal toxic
      shock and related complications after thirty-two days of treatment in intensive
      care unit. Necrotizing fasciitis is an uncommon but life-threatening complication
      in immunocompromised hosts. Tissue infections in cat bite wounds are commonly
      caused by pathogenic bacterium known as Pasteurella multocida. Group A
      streptococcal infections are not reported following cat bites. A high index of
      suspicion must be maintained to suspect group A streptococcal associated
      necrotizing fasciitis following cat bites and an early medical and surgical
      intervention should be made for any best possible outcome.

PMID- 29348947
TI  - Effects of Mifepristone on Nonalcoholic Fatty Liver Disease in a Patient with a
      Cortisol-Secreting Adrenal Adenoma.
AB  - Cushing syndrome (CS), a complex, multisystemic condition resulting from
      prolonged exposure to cortisol, is frequently associated with nonalcoholic fatty
      liver disease (NAFLD). In patients with adrenal adenoma(s) and NAFLD, it is
      essential to rule out coexisting endocrine disorders like CS, so that the
      underlying condition can be properly addressed. We report a case of a 49-year-old
      woman with a history of hypertension, prediabetes, dyslipidemia, biopsy-confirmed
      steatohepatitis, and benign adrenal adenoma, who was referred for endocrine work
      up for persistent weight gain. Overt Cushing features were absent. Biochemical
      evaluation revealed nonsuppressed cortisol on multiple 1-mg dexamethasone
      suppression tests, suppressed adrenocorticotropic hormone, and low
      dehydroepiandrosterone sulfate. The patient initially declined surgery and was
      treated with mifepristone, a competitive glucocorticoid receptor antagonist. In
      addition to improvements in weight and hypertension, substantial reductions in
      her liver enzymes were noted, with complete normalization by 20 weeks of therapy.
      This case suggests that autonomous cortisol secretion from adrenal adenoma(s)
      could contribute to the metabolic and liver abnormalities in patients with NAFLD.
      In conclusion, successful management of CS with mifepristone led to marked
      improvement in the liver enzymes of a patient with long-standing NAFLD.

PMID- 29348948
TI  - Granulomatous Pancreas: A Case Report of Pancreatic Sarcoid.
AB  - Sarcoidosis is a chronic, systemic, noncaseating granulomatous disease process of
      unknown etiology. Sarcoidosis most commonly manifests in the lungs; however,
      gastrointestinal manifestations can occur. If in the GI tract, it is almost
      always found in the liver. Solitary pancreatic lesions are extremely rare, with
      less than 50 documented cases found in the literature. We present a case of a 61
      year-old female, with a past medical history of sarcoidosis, who presented to the
      ER with unexpected weight loss, scleral icterus, right upper quadrant pain, and
      epigastric and back pain. US and MRI found a dilated common bile duct and mild
      dilation of the pancreatic duct, as well as a focal prominence in the head of the
      pancreas surrounded by areas of atrophy. A pancreaticoduodenectomy procedure was
      performed and fresh frozen sections were taken. The pathologist made a diagnosis
      of nonnecrotizing granulomatous pancreatitis. Pancreatic sarcoid is often
      asymptomatic and a benign finding on autopsy; however, clinicians should be
      mindful of pancreatic involvement when working up differential diagnosis for
      pancreatic masses.

PMID- 29348949
TI  - Cetuximab-Associated Crescentic Diffuse Proliferative Glomerulonephritis.
AB  - Cetuximab-induced nephrotoxicity is very rare, occurring in less than 1% of
      colorectal cancer patients and not defined in other populations. We report a rare
      case of crescentic diffuse proliferative glomerulonephritis (GN) that developed
      in close temporal association with cetuximab treatment. A 65-year-old female
      recently completed chemotherapy with cetuximab treatment for moderately
      differentiated oral squamous cell carcinoma. She was admitted with acute renal
      failure and nephrotic-range proteinuria. Laboratory data showed serum creatinine
      of 6.6 mg/dl and urinalysis showed proteinuria, moderate hemoglobinuria, hyaline
      casts (41/LPF), WBC (28/HPF), and RBC (81/HPF). Serologic studies were negative
      for ANA, anti-GBM, ANCA, hepatitis B, and hepatitis C. Serum C3 and C4 level were
      normal. Renal biopsy showed crescentic diffuse proliferative GN with focal
      features of thrombotic microangiopathy. Patient was started on cyclophosphamide
      and steroids. Her renal function did not improve on day 8 and she was started on
      hemodialysis. Previous reports suggest that EGFR-targeting medications can
      possibly trigger or exacerbate an IgA-mediated glomerular process leading to
      renal failure. This case suggests that cetuximab therapy may have triggered or
      exacerbated a severe glomerular injury with an unfavorable outcome. Treating
      physicians should maintain a high degree of caution and monitor renal function in
      patients on EGFR inhibitors.

PMID- 29348950
TI  - Carotid Endarterectomy in a Patient with Severe Internal Carotid Artery Stenosis
      with Persistent Trigeminal Artery and Ischemia of the Anterior and Posterior
      Circulation.
AB  - Occurrence of cerebral ischemia in the posterior circulation as a result of
      severe internal carotid artery disease and persistent trigeminal artery is rare.
      An 81-year-old man with medical history of hypertension and ischemic stroke
      presented with dizziness, nausea, and mild dysarthria. Magnetic resonance imaging
      of the brain revealed acute infarcts in the left internal carotid artery
      territory. CT angiogram revealed a persistent trigeminal artery (PTA) and severe
      atherosclerosis. The patient developed new neurological symptoms and repeat
      imaging revealed new acute infarcts in the PTA distribution. After undergoing a
      left carotid endarterectomy with no complications, the patient was discharged to
      a skilled nursing facility with no recurrence of ischemic stroke. This case adds
      a rare complication of an infrequent vascular anomaly to the limited body of the
      literature.

PMID- 29348951
TI  - Prenatal Diagnosis of Thoracoschisis and Review of Literature.
AB  - Thoracoschisis is a rare congenital malformation characterized by herniation of
      the abdominal content through a defect in the thorax. There are previously 12
      reported cases, most discussing the postnatal findings and management. Here we
      describe a case of left thoracoschisis with associated upper limb abnormality
      which was diagnosed antenatally with the aid of 3D ultrasound.

PMID- 29348952
TI  - Persistent Corneal Decompensation due to Anterior Dislocation of Soemmering Ring
      Cataract.
AB  - Purpose: We present a case of a patient with Soemmering ring after cataract
      surgery and a potential complication that can arise as a result of its presence.
      Observations: A patient with history of ruptured globe status after repair and
      lensectomy, complicated by aphakic secondary open angle glaucoma, was referred
      for management of second injury to the same eye. This injury resulted in
      Soemmering ring dislocation into the anterior chamber. The cortical material
      caused a significant increase in intraocular pressure and corneal decompensation.
      Surgical removal of the Soemmering ring and Ahmed glaucoma tube implant was
      performed with control of intraocular pressures; however corneal edema could not
      be reversed. Conclusions and Importance: This case report illustrates the serious
      consequences that can be caused by Soemmering rings without early surgical
      intervention. Care must be taken to completely remove cortical material during
      cataract surgery to prevent their formation.

PMID- 29348953
TI  - Multimodal Images of Acute Central Retinal Artery Occlusion.
AB  - Two illustrative cases of acute central retinal artery occlusion (CRAO) are
      presented with multimodal imaging, including fluorescein angiography (FA) and
      commercially available optical coherence tomography angiography (OCT-A). In both
      patients, retinal ischemia was imaged well using both FA and OCT-A, and the two
      imaging studies provided comparable pictures. OCT-A provides useful information
      for the diagnosis and management of patients with acute CRAO, without the need
      for dye injection.

PMID- 29348954
TI  - Managing an Acute and Chronic Periprosthetic Infection.
AB  - A case report of a 65-year-old female with a history of right total hip
      arthroplasty (THA) in 2007 and left THA in 2009 was presented. She consulted with
      our institution for the first time, on December 2013, for right hip pain and
      fistula on the THA incision. It was managed as a chronic infection, so a two
      stage revision was performed. First-time intraoperative cultures were positive
      for Staphylococcus aureus (3/5) and Proteus mirabilis (2/5). Three weeks after
      the second half of the review, it evolved with acute fever and pain in relation
      to right hip. No antibiotics were used, arthrocentesis was performed, and a
      coagulase-negative staphylococci multisensible was isolated at the 5th day. Since
      the germ was different from the first revision, it was decided to perform a one
      stage revision. One year after the first review, the patient has no local signs
      of infection and presents ESV and RPC in normal limits. The indication and
      management of periprosthetic infections are discussed.

PMID- 29348955
TI  - Pseudomonas aeruginosa Septic Arthritis and Osteomyelitis after Closed Reduction
      and Percutaneous Pinning of a Supracondylar Humerus Fracture: A Case Report and
      Review of the Literature.
AB  - Infectious complications of closed reduction and percutaneous pinning of
      supracondylar humerus fractures are exceedingly rare. Although postoperative
      Pseudomonas infection is a feared complication associated with noncompliance and
      a wet cast, there are no reports in the literature of this occurring. We present
      the devastating complication of a pediatric patient who developed Pseudomonas
      aeruginosa subperiosteal abscess, osteomyelitis, and elbow septic arthritis after
      presenting to the clinic multiple times with a wet cast after closed reduction
      and percutaneous pinning of a supracondylar humerus fracture. We describe the
      treatment course for this patient, followed by the sequelae of posterolateral
      rotary instability. This case not only confirms that patients can get Pseudomonas
      infections if they get their cast wet but also stresses the importance of patient
      communication and compliance in preventing unfortunate complications.

PMID- 29348956
TI  - Nodular Lymphocyte-Predominant Hodgkin Lymphoma in Progressive Transformation of
      Germinal Centers.
AB  - Nodular lymphocyte-predominant Hodgkin lymphoma is an uncommon variant of Hodgkin
      lymphoma. Progressive transformation of germinal centers has been associated with
      and can develop prior to, concurrent with, or after the diagnosis of nodular
      lymphocyte-predominant Hodgkin lymphoma. We present a patient with a history of
      progressive transformation of germinal centers of the right parotid who presented
      4 years later with ipsilateral parotid mass and cervical adenopathy. Knowledge of
      her previous diagnosis raised our concern for lymphoma, influenced our surgical
      management, and spared the patient additional surgery with risk of facial nerve
      injury inherent in revision parotidectomy.

PMID- 29348957
TI  - Acute Hematogenous Osteomyelitis in a Five-Month-Old Male with Rickets.
AB  - Osteomyelitis is defined as an infection of the bone, bone marrow, and the
      surrounding soft tissues. Most cases of acute hematogenous osteomyelitis in
      children are caused by Gram-positive bacteria, principally Staphylococcus aureus.
      We present a case where a 5-month-old male had an acute onset of decreased
      movement of his left leg and increased irritability and was subsequently
      diagnosed with rickets and hematogenous osteomyelitis with bacteremia. The case
      explores a possible association between hematogenous osteomyelitis and rickets.

PMID- 29348958
TI  - Seronegative Myasthenia Gravis, as a Rare Autoimmune Condition in Turner
      Syndrome.
AB  - Girls with Turner syndrome (TS), especially with isochromosome 46,X,i(X)(q10),
      are prone to develop autoimmunity. Associations of several autoimmune conditions
      with TS have been frequently described in the past. However, the unique
      combination of TS and myasthenia gravis (MG) has been reported only once before
      in a girl with mosaic monosomy 45,X/46,XX. Here, we present the second case of a
      girl affected with seronegative MG but with mosaic isochromosome TS. This is a
      child with developmental delay presented with muscle weakness, frequent fall, and
      bilateral ptosis. Diagnosis of MG was made based on positive Tensilon and
      electromyography tests and excellent response to intravenous immunoglobulin. At
      the age of 11 years due to short stature and developmental delay, a karyotype was
      done and revealed the mosaic isochromosome 45,X/46,X,i(X)(q10). Overall,
      clinicians should be aware of the vulnerability of girls with TS to autoimmunity,
      especially if the isochromosome 46,X,i(X)(q10) karyotype is identified.
      Furthermore, if a child with TS develops muscle weakness, ptosis, or
      ophthalmoplegia, MG should also be included in the differential diagnosis,
      particularly if other concurrent autoimmune conditions are present.

PMID- 29348959
TI  - Malignant Tumours Mimicking Complicated Appendicitis and Discovered upon Follow
      Up after Percutaneous Drainage: A Case of Two Patients.
AB  - The conservative management of periappendiceal abscesses is gaining favour due to
      decreased morbidity and improved clinical outcomes for patients. Occasionally
      however an abscess can mask underlying sinister pathology. In this article, we
      highlight two cases of appendiceal adenocarcinoma that were initially diagnosed
      as periappendiceal abscesses and managed conservatively with percutaneous
      drainage. We also discuss clinical and imaging features that may assist with
      identifying a hidden malignancy when presented in these situations.

PMID- 29348960
TI  - Inflammatory Fibroid Polyp: An Unusual Cause of Ileoileal Intussusception.
AB  - Inflammatory fibroid polyp (IFP), or Vanek's tumor, is a rare benign lesion of
      the gastrointestinal tract. Clinical manifestations of IFP vary based on size and
      location within the GI tract. This case describes a patient who presented with
      hematochezia and abdominal pain. Computed tomography revealed ileoileal
      intussusception without a clear lead point. The patient underwent resection of
      the intussuscepted small bowel with primary anastomosis. A large polypoid mass
      was identified as the pathological lead point. Histopathological and
      immunohistochemical analysis revealed an IFP. Review of the literature indicates
      that early surgical intervention is the treatment of choice for intussusception
      caused by IFP. Lesions are typically reported as solitary, and resection is
      curative.

PMID- 29348961
TI  - Mesenchymal Hamartoma of the Liver: Complete Excision Always Necessary.
AB  - Mesenchymal hamartoma (MH) is not an uncommon tumor of the liver in the age group
      of 2-10 years. It is the second most common benign liver tumor in children.
      Previously considered a developmental anomaly, newer insights into other theories
      of origin including toxic-metabolic, ischemic, and a true neoplastic process are
      in progress. Previous understanding of a purely benign nature of the tumor is
      being overridden by a real malignant transformation. Complete excision of the
      tumor with clear margins is recommended to achieve a long term cure. A thorough
      understanding of the natural history of these tumors and skillful surgical
      treatment are indispensable elements of care.

PMID- 29348962
TI  - Primary Cytomegalovirus Infection Causing Guillain-Barre Syndrome in a Living
      Renal Allograft Recipient.
AB  - Guillain-Barre Syndrome (GBS) is a common acute autoimmune polyneuropathy in
      adults. There have been few reported cases of Guillain-Barre Syndrome associated
      with active cytomegalovirus (CMV) infection in renal transplant recipients. Here
      we present a case of active CMV viremia inducing Guillain-Barre Syndrome in a
      renal transplant recipient. We discuss the treatment regimen utilized.
      Furthermore, we performed a review of the literature and discuss the cases of CMV
      induced GBS in renal transplant recipients.

PMID- 29348963
TI  - Mucin-Poor Mucinous Tubular and Spindle Cell Carcinoma of the Kidney Presented
      with Multiple Metastases Two Years after Nephrectomy: An Atypical Behaviour of a
      Rare, Indolent Tumour.
AB  - Background: Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare type of
      renal cell carcinoma, whose clinical behaviour and metastatic potential have not
      been fully elucidated to date. There are only a few metastatic cases in the
      literature, which all either featured sarcomatoid differentiation or were
      synchronously metastasised at diagnosis. Case Presentation: We report a case of a
      49-year-old male with end-stage kidney disease on dialysis, presenting with
      multiple osseous metastases of a mucin-poor variant of MTSCC of the kidney,
      without sarcomatoid differentiation, two years after bilateral nephrectomy for
      papillary renal cell carcinoma (RCC) at a curable stage. After retrospectively
      reexamining the initial nephrectomy specimens, the tumour of the right kidney was
      also diagnosed as a mucin-poor variant of MTSCC, while the tumour of the left
      kidney was confirmed as a papillary RCC. Conclusions: It is proposed that MTSCC
      can be associated with end-stage renal disease and that particularly the mucin
      poor variant is easily confused with papillary renal cell carcinoma, as happened
      in this case. Although it is considered as a relatively indolent malign entity,
      it can metastasise even years after successful primary surgical treatment. This
      implies, besides accurate diagnosis, that MTSCC patients should be monitored
      closely in the follow-up period.

PMID- 29348964
TI  - Association between the APOE epsilon4 Allele and Late-Onset Alzheimer's Disease
      in an Ecuadorian Mestizo Population.
AB  - Alzheimer's disease (AD) is the most common neurodegenerative disease. It has two
      main pathological hallmarks: amyloid plaques and neurofibrillary tangles. The
      APOE epsilon4 allele has been recognized as the strongest genetic risk factor for
      late-onset Alzheimer's disease (LOAD) in several populations worldwide, yet the
      risk varies by region and ethnicity. The aims of this study were to describe APOE
      allele and genotype frequencies and examine the relationship between the APOE
      epsilon4 allele and LOAD risk in an Ecuadorian Mestizo population. We carried out
      a case-control study comprising 56 individuals clinically diagnosed with probable
      AD (>=65 years of age) and 58 unrelated healthy control subjects (>=65 years of
      age). Genotyping was performed using the real-time PCR method. Our data showed
      that allelic and genotypic frequencies follow the trends observed in most
      worldwide populations. We also found a high-risk association between APOE
      epsilon4 allele carriers and LOAD (OR = 7.286; 95% CI = 2.824-18.799; p < 0.001).
      Therefore, we concluded that APOE epsilon4 must be considered an important
      genetic risk factor for LOAD in the Ecuadorian Mestizo population. Additionally,
      we suggest that in mixed populations the effects of admixture and ethnic identity
      should be differentiated when evaluating genetic contributions to Alzheimer's
      disease risk.

PMID- 29348965
TI  - Ethanol-Induced Alterations of T Cells and Cytokines after Surgery in a Murine
      Infection Model.
AB  - Background: Interactions between alcohol, infection, and surgery and their effect
      on differentiation and functionality of T helper cells are not yet completely
      understood. We hypothesized that alcohol and surgery disturb differentiation of T
      helper cells and contribute to an impaired immune response. Methods: Mice were
      treated with alcohol for two weeks. Saline treatment served as control. Clinical
      performance and weight were assessed. On day 14, a median laparotomy was
      performed and animals were challenged with Klebsiella pneumoniae intranasally.
      Bacterial load was determined in lungs and blood. T helper cell subpopulations
      and the released cytokines were assessed in lungs, spleens, and plasma. Key
      transcription factors of T cell differentiation were evaluated. Results: Alcohol
      significantly impaired clinical appearance and body weight of animals with
      postsurgical infection (p < 0.05). Bacterial load was significantly higher after
      alcohol treatment (p < 0.05). T helper cell subsets and released cytokine levels
      were significantly altered in lung, but not in spleen. Expression of
      transcription factors of T helper cell lineage commitment did not translate into
      different counts of T helper cells. Conclusions: Alcohol and surgery lead to
      significant cellular and functional modulations of T helper cells during
      postsurgical infection. These effects may contribute to an impaired immune
      response after surgery.

PMID- 29348966
TI  - Development of an Analytical Protocol for Determination of Cyanide in Human
      Biological Samples Based on Application of Ion Chromatography with Pulsed
      Amperometric Detection.
AB  - A simple and accurate ion chromatography (IC) method with pulsed amperometric
      detection (PAD) was proposed for the determination of cyanide ion in urine,
      sweat, and saliva samples. The sample pretreatment relies on alkaline digestion
      and application of Dionex OnGuard II H cartridge. Under the optimized conditions,
      the method showed good linearity in the range of 1-100 MUg/L for urine, 5-100
      MUg/L for saliva, and 3-100 MUg/L for sweat samples with determination
      coefficients (R) > 0.992. Low detection limits (LODs) in the range of 1.8 MUg/L,
      5.1 MUg/L, and 5.8 MUg/L for urine, saliva, and sweat samples, respectively, and
      good repeatability (CV < 3%, n = 3) were obtained. The proposed method has been
      successfully applied to the analysis of human biological samples.

PMID- 29348967
TI  - Quantitative Aspect of Leucophyllum frutescens Fraction before and after
      Encapsulation in Polymeric Nanoparticles.
AB  - The interest on plants has been focalized due to their biological activities.
      Extracts or fractions from plants in biodegradable polymeric nanoparticles (NP)
      provide many advantages on application studies. The encapsulation of the extract
      or fraction in NP is determined for the establishment of the test dose. HPLC
      method is an alternative to calculate this parameter. An analytical method based
      on HPLC for quantification of a hexane fraction from L. frutescens was developed
      and validated according to ICH. Different concentrations of the hexane fraction
      from leaves (HFL) were prepared (100-600 MUg/mL). Linearity, limit of detection,
      limit of quantification, and intra- and interday precision parameters were
      determined. HFL was encapsulated by nanoprecipitation technique and analyzed by
      HPLC for quantitative aspect. The method was linear and precise for the
      quantification of the HFL components. NP size was 190 nm with homogeneous size
      distribution. Through validation method, it was determined that the encapsulation
      of components (1), (2), (3), and (4) was 44, 74, 86, and 97%, respectively. A
      simple, repeatable, and reproducible methodology was developed for the propose of
      quantifying the components of a vegetable material loaded in NP, using as a model
      the hexane fraction of L. frutescens leaves.

PMID- 29348968
TI  - Evaluation of Root Canal Morphology of Mandibular First and Second Premolars
      Using Cone Beam Computed Tomography in a Defined Group of Dental Patients in
      Iran.
AB  - Background: Successful dental root canal treatments require a complete knowledge
      of dental anatomy and root canal morphology. Materials and Methods: One hundred
      and forty-five cone beam computed tomography (CBCT) images were used to assess
      the anatomy and morphology of mandibular premolars based on Vertucci's
      classifications in a defined group of dental patients in Iran. The number of
      roots and root canals, root canal morphology, root and canal shape (curvature),
      existence of C-shaped canal, and influence of sex on each of these were
      evaluated. A chi-squared test was used for statistical analysis. Results: The
      mandibular first and second premolars had a single root in 95.97% and 100% cases,
      respectively. In the mandibular first premolars, 62.2% were of type I, 0.8% type
      II, 10.9% type III, 0.8% type IV, 20.3% type V, 4.2% type VI, and 0.8% type VII;
      in the second premolars, 78% of canals were of type I, 3% type II, 11% type III,
      7% type V, and 1% type VI. C-shaped canals did not exist in either of the
      premolars. The most prevalent root and canal shape was straight. The most
      prevalent root curvature was a distal curvature in both premolars (71.4% and 74%
      of first and second premolars, resp.). The most prevalent canal curvature was
      lingual and buccal for the first premolars (7.6% each) and distal for the second
      premolars (11%). No significant difference was found between men and women in
      nearly all of the above (P > 0.05). Conclusion: The results suggest that there is
      a need to conduct further evaluations on finding root and canal variations among
      more populations to gain better knowledge prior to root canal treatment.

PMID- 29348969
TI  - Smallholder Farmers' Livelihood Security Options amidst Climate Variability and
      Change in Rural Ghana.
AB  - Farming as a livelihood activity in the Bosomtwe District is threatened by
      climate change. This paper ascertained the alternative livelihood options of
      smallholder farmers against climate variability and change in the Bosomtwe
      District. Using a cross-sectional survey, 152 smallholder farmers were sampled
      from 12 communities using a multistage sampling procedure. The quantitative data
      collected were subjected to binary logistic regression analysis, contingency
      tables, frequencies, and Nagelkerke tests of association, embedded in the
      statistical package for social sciences (SPSS) v.17. The results indicate that
      farmers are resorting to alternative livelihood activities that are less capital
      intensive and require less skill in order to secure income and household food
      supply. Significant determinants of farmers' alternative livelihood are age,
      household size, and household food supply, which were significant at p < .030, p
      < .019, and p < .012, respectively. At a 95% confidence interval (CI), these
      variables had lower to upper CIs for each of the EXP (B), respectively, at CI =
      1.134-12.524, CI = 1.359-30.224, and CI = 1.781-104.561, respectively. The paper
      recommends that government institutes policies that will create opportunities and
      draw on various local/grassroots opportunities and resources to expand farmers'
      asset base for sustainable livelihood strategies.

PMID- 29348970
TI  - Genetic Variability of Exotic Sugarcane Genotypes.
AB  - Sugarcane is the main sugar producing crop in Bangladesh. However, improvement of
      this crop through breeding is limited due to lack of genetic diversity.
      Therefore, genetic variability and diversity assessment are necessarily important
      for the foreign introduced materials. Experiment was conducted with 9 exotic
      sugarcane genotypes at Regional Station, Bangladesh Sugar Crop Research
      Institute, Gazipur, during 2012-13, following RCBD. Data were collected on
      different growth and yield contributing characters. Individual cane weight
      exhibited high genotypic coefficient of variation and phenotypic coefficient of
      variation. Leaf blade length, leaf blade width, fresh leaf weight, dried leaf
      weight, number of tillers, millable cane, bud size, cane diameter, internodes
      number, internode length, plant height, stalk length, brix%, and individual cane
      weight showed high heritability. Individual cane weight showed highly significant
      and positive correlation with cane diameter, internode length, and stalk length,
      whereas path coefficient analysis revealed that cane diameter had maximum
      positive direct effect on individual cane weight followed by internode length,
      number of tillers, and chlorophyll content. Results indicate that the genotypes
      should be selected on the basis of individual cane weight, cane diameter, and
      millable canes number for future breeding to get higher sugarcane yield in
      respect to juice and brix content.

PMID- 29348971
TI  - Ejection fraction improvement and reverse remodeling achieved with
      Sacubitril/Valsartan in heart failure with reduced ejection fraction patients.
AB  - BACKGROUND: Sacubitril/Valsartan has been shown to improve mortality and reduce
      hospitalizations in patients with heart failure with reduced ejection fraction
      (HFrEF). The effect of Sacubitril/Valsartan on ejection fraction (EF) and reverse
      remodeling parameters have not been previously described. METHODS: We performed a
      single-center, retrospective, cohort study of HFrEF patients (n=48) who were
      treated with Sacubitril/Valsartan for a median duration of 3 months
      (Interquartile range 2-6 months). Clinical and echocardiographic parameters were
      reviewed at three time points (pre-baseline which was median of 18 months before
      starting Sacubitril/Valsartan, baseline before treatment started, and post
      Sacubitril/Valsartan). Paired sample t-test and one-way repeated measures ANOVA
      were used for normally distributed data, while Wilcoxon Signed Rank test for non
      normally distributed data. RESULTS: Sacubitril/Valsartan use was associated with
      an average 5% (+/-1.2) increase in EF, from a mean baseline of 25.33% to 30.14%
      (p<0.001) with a median duration of treatment 3 months. There was no significant
      change in mean LVEF over a median duration of 11 months (IQR 5.5-15.5) between
      pre-baseline and baseline time points prior to treatment (p=1.0). The mean
      increase in ejection fraction tended to be marginally greater in the medium/high
      dose cohort as compared to the low dose cohort, with a mean increase of 5.09% (+/
      1.36) and 4.03% (+/-3.17), respectively (p=0.184). There was a 3.36 mm reduction
      in left ventricular end-systolic diameter (p=0.04), a 2.64 mm reduction in left
      ventricular end-diastolic diameter (p=0.02), and a 14.4 g/m2 reduction in left
      ventricular mass index (p<0.01). CONCLUSION: Sacubitril/Valsartan was found to
      improve EF and multiple measures of reverse remodeling beyond the effects of
      concomitant optimal medical therapy. Though these results are encouraging, our
      small sample, observational study requires confirmation in larger cohorts with
      longer follow-up periods.

PMID- 29348972
TI  - Galectin-3 and the incidence of abdominal aortic aneurysm: the atherosclerosis
      risk in communities (ARIC) study.
AB  - Galectin-3, a beta-galactosidase binding lectin, known to be involved in
      inflammatory processes may be associated with abdominal aortic aneurysm (AAA)
      incidence. We examined the prospective association between plasma galectin-3 and
      incident AAA in 9,704 participants of the Atherosclerosis Risk in Communities
      (ARIC) study cohort. We followed participants from 1996-1998 through 2011
      (124,260 person-years) for incident AAA (n=325) defined by ICD codes from
      hospital records and death certificates. At baseline, participants had a mean
      (SD) age of 62.8 (5.7) years; 20.9% were blacks and 56.5% females. The median
      (25th-75th percentile) galectin-3 level was 14.2 (12.0-16.9) ng/mL. Galectin-3
      was correlated positively with most cardiovascular risk factors and with several
      cardiac or inflammatory biomarkers (C-reactive protein, troponin-T, and NT
      proBNP). Using Cox proportional hazards regression adjusted for demographic
      variables and measured AAA risk factors, the hazard ratios for AAA across
      galectin-3 quintiles were 1 (Referent), 1.54 (1.05-2.26), 1.58 (1.05-2.41), 1.76
      (1.15-2.72), and 1.92 (1.22-3.01) (p for trend =0.01). Further adjustment for the
      cardiac and inflammatory biomarkers largely attenuated the association between
      galectin-3 and AAA [AAA hazard ratio for galectin-3 Quintile 5 vs. Quintile 1:
      1.29 (0.81-2.05); p-trend across quintiles =0.44]. In conclusion, higher
      concentrations of plasma galectin-3 were associated with greater incidence of AAA
      though not independent of other cardiac and inflammatory biomarkers. This
      reinforces that galectin-3, a systemic biomarker reflecting inflammation and
      probably increased systemic vascular resistance, is elevated early in the
      pathogenesis of AAA.

PMID- 29348973
TI  - Associations between four types of single-nucleotide polymorphisms in PLA2G7 gene
      and clinical atherosclerosis: a meta-analysis.
AB  - BACKGROUND: Previous studies suggested that some types of single nucleotide
      polymorphisms (SNPs) in PLA2G7 genes, encoding Lp-PLA2 have been reported to
      yield an antiatherogenic effect, but other studies mentioned otherwise. Thus, a
      comprehensive study to explore the effect of SNPs in PLA2G7 genes (V279F, A379V,
      R92H, I198T) toward clinical atherosclerosis is needed. METHODS: We searched
      eligible studies from PubMed, EBSCO, ProQuest, Science Direct, Springer, and
      Cochrane databases for case-control studies to assess the between four types of
      SNPs in PLA2G7 gene with risk of clinical atherosclerosis (CVD = cardiovascular
      disease, CAD = coronary artery disease, PAD = peripheral artery disease, ischemic
      stroke). All studies were assessed under Hardy-Weinberg Equilibrium, an additive
      model. This meta-analysis was performed by RevMan 5.3 to provide pooled estimate
      for odds ratio (ORs) with 95% confidence intervals (95% CIs). RESULTS: Fourteen
      clinical studies met our inclusion criteria. Those included 12,432 patients with
      clinical atherosclerosis and 10,171 were controls. We found that ORs of two
      variants SNPs (V279F, R92H) were associated with clinical atherosclerosis {V279F,
      OR = 0.88 (95% CI, 0.81-0.95); p = 0.0007, I2 = 40%}, {R92H, OR = 1.29 (95% CI,
      1.09-1.53); p = 0.003, I2 = 73%}. Meanwhile, there was no significant
      associations between the other two, A379V {OR = 1.08 (95% CI, 0.93-1.26); p =
      0.31, I2 = 78%} and I198T {OR = 1.12 (95% CI = 0.79-1.59); p = 0.53, I2 = 81%}.
      CONCLUSIONS: These results suggested that V279F polymorphism in PLA2G7 gene has a
      protective effect for clinical atherosclerosis, whereas R92H polymorphism might
      contribute toward increased risk of clinical atherosclerosis.

PMID- 29348974
TI  - Systemic inhibition of neddylation by 3-day MLN4924 treatment regime does not
      impair autophagic flux in mouse hearts and brains.
AB  - Beyond helping the cell survive from energy starvation via self-eating a portion
      of cytoplasm, macroautophagy is also capable of targeted removal of defective
      organelles or cytoplasmic aberrant protein aggregates, thereby playing an
      important role in quality control in the cell. Impaired or suppressed
      macroautophagy activity is associated with the progression from a large subset of
      heart diseases to heart failure and with the development of the vast majority of,
      if not all, neurodegenerative diseases, the leading causes of death and
      disability in humans. Hence, a better understanding of the impact of existing and
      upcoming pharmacotherapies on macroautophagy in the heart and brain will
      undoubtedly benefit the search for safer and more effective treatment to improve
      human health. Neddylation is a recently recognized posttranslational modification
      process that modifies a subset of cellular proteins and is, by virtue of
      regulating Cullin-RING ligases, essential to ~20% ubiquitin-proteasome system
      (UPS)-mediated protein degradation. MLN4924 (Pevonedistat), a specific inhibitor
      of neddylation that promises to become a new anti-malignancy agent, is capable of
      inhibiting UPS-mediated progression of the cell cycle and activating
      macroautophagy in cancer cells. However, no reported study has tested the impact
      of systemic inhibition of neddylation on autophagic activity in a post-mitotic
      organ such as the heart and brain. This study was conducted to fill this gap.
      Sixteen GFP-LC3 transgenic mice of mixed sexes were divided equally into either
      MLN4924-treated or vehicle-treated groups and were treated respectively with
      MLN4924 (30 mg/kg, s.c., twice a day * 3 days) or equal volume of solvent. The
      resultant changes in myocardial levels of neddylated cullin 1 as well as
      autophagic flux in cardiac and brain tissues were assessed. The effectiveness of
      the MLN4924 regime was verified by myocardial accumulation of neddylated cullin
      1. Myocardial LC3-II flux and free GFP levels were comparable between the MLN4924
      and the vehicle groups whereas the protein level of p62, a bona fide substrate of
      macroautophagy, in the brain was significantly decreased by the MLN4924
      treatment. Our data suggest that systemic inhibition of neddylation by a 3-day
      MLN4924 treatment regime does not suppress macroautophagy activities in the heart
      and brain.

PMID- 29348975
TI  - Some different treatment of sandal burns of the hand in children.
AB  - The hands account for less than 5% of total body surface area, but loss of the
      hand constitutes a 57% loss of function for the whole person. In Central Asia,
      and particularly in Uzbekistan, many episodes of burns take place at homes
      because of using sandal heaters. During a 16-year period (1992-2007), 61 patients
      with severe sandal burns of the hand were treated at the Burn department of
      RSCUMA and Samarkand Inter-Regional Burn Center, Uzbekistan. The main goal of
      this work was to present the most complete information about sandal burns of the
      hand and discuss the most effective methods of treatment for sandal burns. As a
      result of using this method of treatment for burned children in our practice, the
      percentage of post burn consequences, such as the impact on mobility and growth
      of the extremities, was greatly reduced.

PMID- 29348977
TI  - Treatment in the healing of burns with a cold plasma source.
AB  - A cold plasma produced with helium gas was applied to two second-degree burns
      produced with boiling oil. These burns were located on a thigh and a shin of a 59
      years-old male person. After the first treatment as benefit the patient neither
      presented itching nor pain and, after the second treatment, the patient presented
      new tissue. This result opens the possibilities of the application of a cold
      plasma source to health burns.

PMID- 29348976
TI  - The validity and reliability of using ultrasound elastography to measure
      cutaneous stiffness, a systematic review.
AB  - BACKGROUND: Ultrasound elastography is an imaging technology which can
      objectively and non-invasively assess tissue stiffness. It is emerging as a
      useful marker for disease diagnosis, progression and treatment efficacy.
      OBJECTIVE: To examine current, published research evaluating the use of
      ultrasound elastography for the measurement of cutaneous or subcutaneous
      stiffness and to determine the level of validity and reliability, recommended
      methodologies and limitations. METHODS: MEDLINE, Web of science and Scopus were
      systematically searched in August 2016 to identify original articles evaluating
      the use of ultrasound elastography to assess cutaneous stiffness. Relevant
      studies were then quality evaluated using the Quality Assessment of Diagnostic
      Accuracy Studies v 2 (QUADAS-2) tool and the Quality Appraisal of Reliability
      Studies (QAREL). RESULTS: From a total of 688 articles, 14 met the inclusion
      criteria for full review. Within the 14 studies, elastography was used to
      evaluate tumors, systemic sclerosis, lymphedema, abscess, and post-radiation neck
      fibrosis. Only three robust studies demonstrated good interrater reliability,
      whereas all validity studies had low sample sizes and demonstrated risks of bias.
      CONCLUSION: Robust evidence supporting the use of ultrasound elastography as a
      diagnostic tool in cutaneous conditions is low, however, initial indicators
      support further research to establish the utility of ultrasound elastography in
      dermatology.

PMID- 29348978
TI  - The effect of ambient lighting on Laser Doppler Imaging of a standardized
      cutaneous injury model.
AB  - OBJECTIVE: The aim of this study was to investigate the potential confounding
      effects of four different types of ambient lighting on the results of Laser
      Doppler Imaging (LDI) of a standardized cutaneous injury model. METHODS: After
      applying a mechanical stimulus to the anterior forearm of a healthy volunteer and
      inducing a wheal and arteriolar flare (the Triple response), we used a Laser
      Doppler Line Scanner (LDLS) to image the forearm under four different types of
      ambient lighting: light-emitting-diode (LED), compact fluorescent lighting (CFL),
      halogen, daylight, and darkness as a control. A spectrometer was used to measure
      the intensity of light energy at 785 nm, the wavelength used by the scanner for
      measurement under each type of ambient lighting. RESULTS: Neither the LED nor CFL
      bulbs emitted detectable light energy at a wavelength of 785 nm. The color-based
      representation of arbitrary perfusion unit (APU) values of the Triple response
      measured by the scanner was similar between darkness, LED, and CFL light.
      Daylight emitted 2 mW at 785 nm, with a slight variation tending more towards
      lower APU values compared to darkness. Halogen lighting emitted 6 mW of light
      energy at 785 nm rendering the color-based representation impossible to
      interpret. CONCLUSIONS: Halogen lighting and daylight have the potential to
      confound results of LDI of cutaneous injuries whereas LED and CFL lighting did
      not. Any potential sources of daylight should be reduced and halogen lighting
      completely covered or turned off prior to wound imaging.

PMID- 29348979
TI  - Simplified estimation of binding parameters based on image-derived reference
      tissue models for dopamine transporter bindings in non-human primates using
      [18F]FE-PE2I and PET.
AB  - The aim of this study on dopamine transporter binding by [18F]FE-PE2I and PET was
      to describe an image-derived approach using reference tissue models: the Logan
      DVR approach and simplified reference tissue model (SRTM), the features of which
      were simple to operate and precise in the measurements. Using the approach, the
      authors sought to obtain binding images and parameters. [18F]FE-PE2I and dynamic
      PET as well as an MRI was performed on three rhesus monkeys, and metabolite
      corrected arterial plasma inputs were obtained. After co-registering of PET to MR
      images, both image sets were resliced. The time-activity curve of the cerebellum
      was used as indirect input, and binding parametric images were computed voxel-by
      voxel. Voxel-wise linear calculations were used for the Logan DVR approach, and
      nonlinear least squares fittings for the SRTM. To determine the best linear
      regression in the Logan DVR approach, the distribution volume ratio was obtained
      using the optimal starting frame analysis. The obtained binding parameters were
      compared with those obtained by the other independent ROI-based numerical
      approaches: two-tissue compartment model (2TCM), Logan DVR approach and SRTM
      using PMOD software. Binding potentials (BP) obtained by the present approach
      agreed well with those obtained by ROI-based numerical approaches, although
      reference tissue models tended to underestimate the BP value than 2TCM. Image
      derived Logan approach provided a low-noise image, the computation time was
      short, and the error in the optimal starting frame analysis was small. The
      present approach provides a high-quality binding parametric image and reliable
      parameter value easily.

PMID- 29348980
TI  - The value of FDG PET/CT for follow-up of patients with melanoma: a retrospective
      analysis.
AB  - The incidence of melanoma (MM) is among the fastest rising cancers in the western
      countries. Positron Emission Tomography with Computed Tomography (PET/CT) is a
      valuable non-invasive tool for the diagnosis and staging of patients with MM.
      However, research on the value of PET/CT in follow-up of melanoma patients is
      limited. This study assesses the diagnostic value of PET/CT for follow-up after
      melanoma surgery. This retrospective study includes patients with MM who
      performed at least one PET/CT scan after initial surgery and staging. PET/CT
      findings were compared to histology, MRI or fine needle aspiration (FNA) to
      estimate the diagnostic accuracy. The diagnostic performance of PET/CT performed
      in patients with and without a clinical suspicion of relapse was compared. 238
      patients (526 scans) were included. Of the 526 scans 130 (25%) scans were PET
      positive, 365 (69%) PET-negative, and 28 (5%) had equivocal findings. Sensitivity
      was 89% [0.82-0.94], specificity 92% [0.89-0.95], positive and negative
      predictive values of 78% [0.70-0.84] and 97% [0.94-0.98] respectively. When
      stratified for reason of referral there was no statistical significant difference
      in the diagnostic accuracy of PET/CT between patients referred with or without a
      clinical suspicion of relapse. This study demonstrates that PET/CT despite a
      moderate sensitivity has a high negative predictive value in the follow-up of
      melanoma patients. Thus, a negative PET/CT-scan essentially rules out relapse.
      However, the frequency of false positive findings is relatively high, especially
      among patients undergoing a "routine" PET/CT with no clinical suspicion of
      relapse, potentially causing anxiety and leading to further diagnostic
      procedures.

PMID- 29348981
TI  - Development of a clinically feasible [11C]PE2I PET method for differential
      diagnosis of parkinsonism using reduced scan duration and automated reference
      region extraction.
AB  - [11C]PE2I is a highly selective dopamine transporter PET ligand. Parametric
      images based on dynamic [11C]PE2I scans, showing dopamine transporter
      availability (BPND) and relative cerebral blood flow (R1), can be used in
      differential diagnosis of parkinsonism. This work aimed to investigate a
      shortened scan duration and automated generation of parametric images which are
      two prerequisites for routine clinical application. Twelve subjects with
      parkinsonism and seventeen healthy controls underwent 80 min dynamic [11C]PE2I
      PET scans. BPND and R1 images were generated using cerebellum reference region
      defined on a co-registered MRI, as well as a supervised cluster analysis (SVCA)
      based reference. Initial 20, 30 and 40 min of the scans were extracted and images
      of standardized uptake value ratio (SUVR) and R1 were computed using MRI- and
      SVCA-based reference. Correlation was high between striatal 80 min MRI-based BPND
      and 40 min SVCA-based SUVR-1 (R2=0.95). High correlation was also found between
      R1 values in striatal and limbic regions (R2>=0.91) whereas correlation was
      moderate for cortical regions (R2=0.71). The results indicate that dynamic
      [11C]PE2I scans can be restricted to 40 min and that SVCA can be used for
      automatic extraction of a reference region. These outcomes will support routine
      applications of [11C]PE2I PET in clinical settings.

PMID- 29348982
TI  - Pictorial atlas of symptomatic accessory ossicles by 18F-Sodium Fluoride (NaF)
      PET-CT.
AB  - Accessory ossicles are developmental variants which are often asymptomatic. When
      incidentally picked up on imaging, they are often inconsequential and rarely a
      cause for concern. However, they may cause pain or discomfort due to trauma,
      altered stress, and over-activity. Nuclear scintigraphy may play a role in the
      diagnosis and localizing pain generators. 18F-Sodium Fluoride (NaF) is a PET
      imaging agent used in bone imaging. Although commonly used in imaging patients
      with cancer imaging malignancy, 18F-NaF may be useful in the evaluation of benign
      bone and joint conditions. In this article, we would like to present a spectrum
      of clinical cases and review the potential diagnostic utility of 18F-NaF in the
      assessment of symptomatic accessory ossicles in patients referred for staging
      cancers.

PMID- 29348983
TI  - Sparse domain approaches in dynamic SPECT imaging with high-performance
      computing.
AB  - Iterative reconstruction algorithms often have relatively large computation time
      affecting their clinical deployment. This is especially true for 4D
      reconstruction in dynamic imaging (DI). In this work, we have shown how sparse
      domain approaches and parallelization for static 3D image reconstruction and 4D
      dynamic image reconstruction (directly from sinogram) in Single Photon Emission
      Computed Tomography (SPECT), without any intermediate 3D reconstructions, can
      improve computational efficiency. DI in SPECT is one of the hardest inverse
      problems in medical image reconstruction area and slow reconstruction is a
      challenge for this promising protocol. Our work hopefully, paves a new direction
      toward making DI in SPECT clinically viable. Our 4D reconstruction also is a
      novel application of non-negative matrix factorization (NNMF) in an inverse
      problem.

PMID- 29348984
TI  - Human immune system during sleep.
AB  - A joint function of tissues, organs and cells for the protection of body develops
      immune system. The human immune response against various infections during sleep,
      its mechanism, neuroimmune interactions, immunoregulatory effect of sleep along
      with sleep deprivation and role of cytokines in sleep deprivation were addressed.
      It is revealed that human immune system and sleep both are associated and
      influenced by each other. Sleep deprivation makes a living body susceptible to
      many infectious agents. In the result, immune system of human body is altered by
      releasing immunomodulators in the response of infections as reported by various
      researchers. Basic reasons and mechanisms of most of the poor sleep networks and
      release of proinflammatory modulators are still uncertain. The current situation
      requires improved sleep habits to make immune system efficient for a healthy
      life.

PMID- 29348985
TI  - The effect and safety of diacerein in patients with type 2 diabetes mellitus : a
      systematic review and meta-analysis.
AB  - : The Background: Diacerein has been proposed as a treatment option for
      management of type 2 diabetes due to its anti-inflammatory properties. PURPOSE:
      The aim of this systematic review and meta-analysis of randomized controlled
      trials (RCTs) is to examine the effect and safety of diacerein in patients with
      type 2 diabetes. DATA SOURCES AND STUDY SELECTION: We searched Pubmed, Embase,
      and Cochrane Library for RCTs published from database inception to September
      2017. DATA EXTRACTION AND DATA SYNTHESIS: Among 44 studies that were initially
      identified, four were eligible and were included in the following analysis.
      Diacerein significantly reduced fasting glycemia [weighted mean differences (WMD)
      -0.66, 95% confidence interval (95% CI) -1.16 to -0.16] and glycated hemoglobin
      A1c (HbA1c ) (WMD -0.85, 95% CI -1.44 to -0.26). And the patients with a
      diacerein supplementation duration of <=12 weeks had a greater decrease of
      fasting glycemia and HbA1c than the supplementation duration of >12 weeks.
      Furthermore, compared with placebo, diacerein revealed a significant increase in
      the relative risk (RR) of gastrointestinal symptoms (RR=2.50, 95% CI: 1.10 to
      5.65), especially in the study subgroup with supplementation duration of >12
      weeks (RR=4.01, 95% CI: 2.32 to 6.95). LIMITATIONS: The sample size was
      relatively small and the duration of included studies was short so that the
      treatment efficacy and safety for longer duration was unknown. CONCLUSIONS:
      Although further studies are needed, our findings clearly provide support to the
      use of diacerein in the clinical management of subjects with type 2 diabetes.

PMID- 29348986
TI  - An immunohistochemical analysis of folate receptor beta expression and
      distribution in giant cell arteritis - a pilot study.
AB  - BACKGROUND: Giant cell arteritis (GCA) is a chronic vasculitis of large and
      medium vessels in which no targetable biomarkers exist to allow selective
      treatment, predict disease activity and monitor therapeutic responses. The
      accessibility of the temporal artery (TA) for biopsy allows morphologic studies
      to characterize macrophages and T cells in the microenvironment of the arterial
      wall. We evaluated the expression of folate receptor beta (FRB), a candidate
      diagnostic/therapeutic biomarker, compared its expression with key macrophage
      markers and correlated it with GCA severity. METHODS: Formalin-fixed paraffin
      embedded tissue sections were examined from 6 patients with GCA and 2 controls.
      Immunohistochemistry was performed using FRB, ETB, CD68 and CD3 antibodies to
      evaluate for activated macrophages and T cells, assess FRB distribution along the
      intima, media and adventitial layers and composition of inflammatory infiltrates.
      We compared the expression of FRB, ETB and CD68 in GCA versus negative controls
      and in severe (with visual loss) versus mild (without visual loss) disease.
      RESULTS: In GCA, moderate to severe inflammation was accompanied by >90%
      destruction of the internal elastic lamina. Macrophages comprised 36.3 +/- 4.1%
      while CD3+ lymphocytes accounted for 61.7 +/- 4.1% of total leukocytes. FRB was
      selectively expressed in macrophages and localized to the adventitia. GCA
      patients had marginally increased median FRB (9.8 cells/hpf vs. 0; p=0.095), ETB
      (20.5 vs. 0; p=0.095) and CD68 (38.8 vs. 5; p=0.071) expression versus controls.
      ETB was found in endothelial cells, smooth muscle cells and macrophages in
      intima/media. FRB positively correlated with ETB (r=0.90; p-0.037) and CD68
      levels (r=0.90; p=0.037). ETB expression positively correlated with CD68 (r=1.0;
      p<0.0001). There was no difference in FRB between severe and mild GCA.
      CONCLUSION: FRB is a potential diagnostic and therapeutic biomarker with
      restricted expression in GCA macrophages. FRB+ macrophages localized to the
      adventitia and their expression correlated with ETB and CD68 macrophages,
      suggesting that they contribute to GCA pathogenesis.

PMID- 29348987
TI  - Rhino-Orbital-Cerebral Mucormycosis: A Fatal Complication of Uncontrolled
      Diabetes Mellitus.
AB  - Mucormycosis is a progressively invasive disease, with a fatal outcome, on late
      presentation. A 38-year-old female presented with diabetic ketoacidosis with
      right eye ptosis and a frozen globe without any signs of inflammation,
      externally. She underwent transnasal endoscopic debridement of paranasal sinuses
      and exenteration of the right eye. The histopathology specimen revealed the
      growth of mucormycosis. She was treated with intravenous (IV) amphotericin B, IV
      insulin, and extensive debridement surgery, but had an unfavorable outcome due to
      rapid mucor invasion to the brain.

PMID- 29348988
TI  - Anal Squamous Cell Carcinoma in a Patient with Myasthenia Gravis: Is
      Immunosuppression the Main Underlying Etiology?
AB  - Patients who are immunocompromised by diseases such as human immunodeficiency
      virus (HIV) infection are more prone to develop some malignancies such as
      Kaposi's sarcoma and central nervous system (CNS) lymphomas. Historically, anal
      squamous cell carcinoma (SCC) was also included on the list as an acquired
      immunodeficiency syndrome (AIDs)-defining cancer.  Similarly, compromised immune
      disorders including severe immunosuppression, haematologic malignancies, and
      solid organ transplantation have been identified as important risk factors for
      the development of anal SCC. Review of the medical literature showed only
      sporadic cases of anal SCC in patients with pre-existing myasthenia gravis (MG),
      with or without thymoma.  We present here a case of anal SCC in a patient with
      several years history of MG who was receiving intravenous immunoglobulin (IVIG). 
      We believe this association is explained by the autoimmune nature of the disease
      and the use of immunosuppressive medications to treat it. To further support our
      case, we also present a review of the literature associating anal SCC with MG.

PMID- 29348989
TI  - Signs and Symptoms of Acoustic Neuroma at Initial Presentation: An Exploratory
      Analysis.
AB  - Introduction The objective of this study was to describe the most common clinical
      features associated with an acoustic neuroma diagnosis and to identify those
      features associated with larger tumour size at initial diagnosis. Methods The
      clinical information of 945 consecutive patients diagnosed with acoustic neuroma
      at a single centre between 1992 and 2015 was analysed. Clinical features were
      examined and the relationship between these features and tumour size (>2.5 cm)
      was analysed using descriptive statistics and logistic regression analysis.
      Statistical analysis was performed in R version 3.1.1. Results The most common
      presenting symptom was a unilateral hearing loss in 752 patients (80%), with a
      progressive pattern in 90% of these cases. The second most common presenting
      symptom was unilateral tinnitus, accounting for 6.3%, while ataxia, vertigo and
      headache accounted for 3.8%, 3.4% and 2%, respectively. The diagnosis of acoustic
      neuroma was an incidental finding in 20 patients (2.1%). Temporal analysis
      demonstrated a downward trend in the number of patients presenting with hearing
      loss and an increased proportion of patients presenting with other symptoms. On
      multivariate analysis, larger tumour size was associated with abnormal tandem
      gait (odds ratio 8.9, p=0.02), subjective facial weakness (odds ratio 5.3, p<
      0.001), abnormal facial sensation on examination (odds ratio 3.0, p=0.03) and
      headache (odds ratio 2.6, p< 0.001). Conclusion The majority of patients with
      acoustic neuroma present with the classic, progressive, unilateral hearing loss.
      However, the pattern of presentation in acoustic neuroma patients is changing.
      Features in the history indicative of a larger tumour are headaches and
      subjective facial weakness, whilst concerning features on examination are
      abnormal tandem gait and altered facial sensation.

PMID- 29348990
TI  - Hypercalcemia of Malignancy: An Emergency Medicine Simulation.
AB  - Hypercalcemia is a poor prognostic factor associated with malignancy. The signs
      and symptoms of hypercalcemia that the patients present to the emergency
      department are vague and often overlap with the general symptoms of cancer itself
      or the adverse effects of the chemotherapy. Given that the development of
      hypercalcemia of malignancy can present with imminent danger to the patient and
      is a treatable condition, emergency physicians should know how to recognize and
      treat it. It also marks a time at which discussions regarding plans of care
      should be initiated with the patients. In this report, we describe a simulation
      case that can be used to train emergency medicine residents to both recognize and
      treat hypercalcemia of malignancy and to initiate the discussion of goals of
      care.

PMID- 29348991
TI  - Medical Expulsive Therapy for Distal Ureteral Stones: Tamsulosin Versus Silodosin
      in the Turkish Population.
AB  - Introduction Our aim was to contribute a study that includes a higher patient
      population to the limited number of studies comparing tamsulosin and silodosin in
      the treatment of distal ureteral stones. Material and methods Patients who
      presented with renal colic to the urology emergency clinic and were diagnosed
      with ureteral stones and followed-up with conservative treatment between January
      2010 and January 2016 were retrospectively screened. According to the inclusion
      exclusion criteria, the patients were divided into three groups. Group 1: 150
      patients followed with watchful waiting (WW), Group 2: 156 patients who received
      0.4 mg of tamsulosin daily, and Group 3: 159 patients who received 8 mg of
      silodosin daily. The side effects of the used drugs, duration of stone reduction,
      and expulsion rates were evaluated and compared separately. Results A total of
      465 patients were included in the study. No statistically significant difference
      was found in terms of age, gender, and stone size among the groups. The patient
      characteristics and results are shown in Table 1. The differences in stone
      expulsion rate between the groups in the first week were calculated using the Chi
      square test and found to be non-significant (p = 0.155); whereas, the stone
      expulsion rates between Group 1 versus Group 2 and Group 1 versus Group 3 were
      found to be significantly different after the second and third week. Conclusion
      According to our results, no statistically significant superiority between
      tamsulosin and silodosin was shown in the treatment of distal ureteral stones in
      the Turkish population.

PMID- 29348992
TI  - Hernioscopy in Incarcerated Inguinal Hernia Spontaneously Reduced after General
      Anesthesia Induction.
AB  - Hernioscopy is essentially hernia sac laparoscopy. Hernia repair has evolved over
      the years with better outcomes; however, strangulated inguinal hernias are acute
      surgical emergencies which require emergent operative intervention. During
      anesthesia induction and/or after incision, hernia self-reduction is possible,
      with or without compromised bowel, back into the abdominal cavity. It is pivotal
      to examine the bowel to decide on further operative course. A simple alternative
      to unnecessary laparotomy or standard laparoscopy is hernioscopy, which is quite
      uncommon. We present a case of an acute symptomatic strangulated left-sided
      inguinal hernia which got self-reduced during anesthesia induction and was
      successfully repaired after hernioscopy was used to evaluate the incarcerated
      hernia content. We provide a brief review of literature about hernioscopy and an
      algorithm to guide surgeons in emergent cases.

PMID- 29348993
TI  - Delayed Presentation of Cerebral Air Embolism from a Left Atrial-Esophageal
      Fistula: A Case Report and Review of the Literature.
AB  - Air embolism developing from an atrial-esophageal fistula that was created as a
      complication from an atrial ablation procedure is a rare, yet usually fatal
      diagnosis. Neurologic manifestations such as meningitis, altered mental status,
      seizures, strokes, transient ischemic attacks (TIAs), psychiatric changes, and
      coma can ensue. Imaging of the brain might reveal infarcts, cerebral edema, as
      well as signs of pneumocephalus. This case describes a 42-year-old male with
      recent cardiac ablation procedure at an outside hospital for refractory atrial
      fibrillation (A-fib) who presented with altered mental status, dyspnea and
      diaphoresis. His initial head computed tomography (CT) scan revealed
      pneumocephalus. He was started on a heparin drip for a non-ST elevation
      myocardial infarction (NSTEMI), but developed severe coagulopathy. The patient's
      mental status quickly deteriorated. Given recent cardiac ablation procedure, the
      cause of his air embolism was thought to be from a created left atrial-esophageal
      fistula. Despite medical management, he was too unstable to undergo any surgical
      intervention for his atrial-esophageal fistula or to transfer to a hyperbaric
      oxygen therapy center, and expired on the second day following his hospital
      admission. To our knowledge, few reports have been published in the literature
      describing delayed cerebral air embolism from an atrial-esophageal fistula.
      Prompt diagnosis, hyperbaric oxygen therapy, and surgical intervention are
      essential to avoid mortality in these patients. This article aims to increase
      awareness of such a rare, but significant complication.

PMID- 29348994
TI  - The association of Mediterranean diet and exercise modifications with
      anthropometric parameters in a psychiatric community population: A pilot study.
AB  - Weight gain and related metabolic syndrome (MS) are major current issues in
      public health. MS consists of abdominal fat, atherogenic dyslipidemia,
      hypertension, hyperglycemia, insulin resistance, pro-inflammatory and pro
      thrombotic state, and accounts for both cardiovascular diseases and type II
      diabetes mellitus risk factors. Patients affected by psychiatric illness present
      a prevalence of 35-40% of MS. Many studies have shown that Mediterranean diet is
      associated with the reduction of mortality due to cardiovascular and malignant
      diseases, potentially preventing both obesity and type II diabetes mellitus. Our
      pilot study explores the effects of a 12-month healthy lifestyle program
      (Mediterranean diet and mild physical activity) on metabolic and anthropometric
      parameters of patients affected by chronic psychiatric disorders who live in a
      psychiatric community facility. A Mediterranean diet was provided by a senior
      nutritional clinician and adapted by two dieticians, according to the needs and
      preferences of the community population. Concomitantly, a program of moderate
      physical activity, consisting in 30-min walks on level ground 4 days a week, and
      psycho-educational group sessions with educational and therapeutic purposes were
      implemented. The metabolic and anthropometric parameters of our patients improved
      after both 6 (T6) and 12 (T12) months. Body Max Index was statistically
      significantly reduced at T6 and T12, with patients perceiving good quality of
      life. These positive outcomes suggest that a low-cost healthy lifestyle program
      can produce good adherence and feasibility even among patients with chronic
      psychiatric diseases, reducing their risk for MS, cardiovascular diseases and
      other complications.

PMID- 29348995
TI  - Mental health assessment in health checks of participants aged 30-49 years: A
      large-scale cohort study.
AB  - Mental distress is an independent risk factor for illness related impairment.
      Awareness of mental health (MH) allows prevention, but early detection is not
      routinely performed in primary care. This cohort study incorporated MH assessment
      in a health promoting programme. We described the level of poor MH among health
      check participants, explored the potential for early intervention, and the
      potential for reducing social inequality in MH. The study was based on 9767
      randomly selected citizens aged 30-49 years invited to a health check in Denmark
      in 2012-14. A total of 4871 (50%) were included; 49% were men. Poor MH was
      defined as a mental component summary score of <= 35.76 in the SF-12 Health
      Survey. Data was obtained from national health registers and health check.
      Participants with poor MH (9%) were more socioeconomic disadvantaged and had
      poorer health than those with better MH. Two thirds of men (64%) and half of
      women (50%) with poor MH had not received MH care one year before the health
      check. Among those with (presumably) unrecognized MH problems, the proportion of
      participants with disadvantaged socioeconomic characteristics was high (43-55%).
      Four out of five of those with apparently unacknowledged poor MH had seen their
      GP only once or not at all during the one year before the health check. In
      conclusion, MH assessment in health check may help identify yet undiscovered MH
      problems.

PMID- 29348996
TI  - Acculturation and dietary intake pattern among Jamaican immigrants in the US.
AB  - Information on dietary intakes of Jamaican immigrants in the United States is
      sparse. Understanding factors that influence diet is important since diet is
      associated with chronic diseases. This study examined the association between
      acculturation, socio-cultural factors, and dietary pattern among Jamaican
      immigrants in Florida. Jamaican persons 25-64 years who resided in two South
      Florida counties were recruited for participation. A health questionnaire that
      assessed acculturation, dietary pattern, and risk factors for cardiovascular
      disease was administered to participants. Generalized Estimating Equations were
      used to determine associations. Acculturation score was not significantly
      associated with dietary intake pattern (beta = - 0.02 p = 0.07). Age at migration
      was positively associated with traditional dietary pattern (beta = 0.02 p <
      0.01). Persons with 12 or fewer years of education (beta = - 0.55 p < 0.001),
      divorced (beta = - 0.26 p = 0.001), or engaged in less physical activity (beta = 
      0.07 p = 0.01) were more likely to adhere to a traditional diet. Although
      acculturation was not a statistically significant predictor of dietary intake,
      findings show the role of demographic and lifestyle characteristics in
      understanding factors associated with dietary patterns among Jamaicans. Findings
      point to the need to measure traditional dietary intakes among Jamaicans and
      other immigrant groups. Accurate assessment of disease risk among immigrant
      groups will lead to more accurate diet-disease risk assessment and development of
      effective intervention programs.

PMID- 29348997
TI  - Diagnosis and management of a fatal case of sepsis caused by Candida parapsilosis
      sensu stricto in a neonate with omphalocele.
AB  - We present a fatal case of persistent neonatal candidemia by Candida parapsilosis
      following omphalocele, without other anomalies. Despite an encouraging initial
      prognosis, after surgical correction and closure of the abdominal wall the case
      became difficult to treat, as in addition to the exposure of the patient to
      multiple risk factors for candidemia, antifungal therapy apparently was not
      adequate.

PMID- 29348998
TI  - Meniscal Repair With Fibrin Clot Augmentation.
AB  - Meniscal injuries and meniscal loss are associated with changes in knee
      kinematics and loading, ultimately leading to poor functional outcomes and
      increased risk of progression to osteoarthritis. Biomechanical studies have shown
      restored knee function, and clinical studies have reported improved outcomes and
      decreased risk of osteoarthritis after meniscal repair. This has led orthopaedic
      surgeons to try and save the meniscus by repair whenever possible, as shown by
      increasing incidence of meniscal repair surgeries. Historically, meniscal
      lesions, particularly those greater in size and located in the white-white region
      of the meniscus, have been shown to have poor healing. In recent years, there has
      been an increasing interest in the use of biologic agents to help stimulate and
      expedite healing in traditionally more avascular tissue. Preliminary results for
      biologic therapeutic agents, such as platelet rich plasma and bone marrow
      aspirate concentrate, have been encouraging. However, these options are more
      demanding in regard to time, financial burden, resources, and regulations than
      some more classic agents such as fibrin clots. Fibrin clot is readily available,
      easy to use, affordable, and minimally invasive. This Technical Note describes a
      step-by-step and reproducible technique for harvesting, preparation, and using a
      fibrin clot to augment healing of meniscal repairs.

PMID- 29348999
TI  - Open Repair of Quadriceps Tendon With Suture Anchors and Semitendinosus Tendon
      Allograft Augmentation.
AB  - Quadriceps tendinopathy in an increasingly recognized diagnosis can lead to
      quadriceps tendon rupture, especially in the older population. It can be caused
      by repeated micro trauma or also predisposed by systemic diseases such as
      diabetes mellitus and connective tissue disorders that can in turn lead to
      extensor mechanism deficits. Although a trial of conservative treatment is
      advocated, operative treatment should be performed in cases of persistent pain,
      extension deficit, or complete rupture of the tendon. The purpose of this
      Technical Note is to describe in detail a procedure for open repair of a
      quadriceps tendon, with significant degeneration due to quadriceps tendinopathy,
      using suture anchors and semitendinosus tendon allograft augmentation.

PMID- 29349000
TI  - Hamstring Graft Preparation Techniques for Anterior Cruciate Ligament
      Reconstruction.
AB  - Anterior cruciate ligament reconstruction is one of the most commonly performed
      procedures in orthopaedics, with more than 125,000 performed in the United States
      per year. There are several reconstruction graft choices that can be used to
      reconstruct the native anterior cruciate ligament, with autograft hamstring
      tendons being one of the most commonly used. Preparation of a hamstring autograft
      varies depending on patient characteristics and physician preference. The purpose
      of this Technical Note is to describe in detail different variants of hamstring
      graft preparation techniques that are commonly used in practice.

PMID- 29349001
TI  - Medial Closing-Wedge Distal Femoral Osteotomy with Medial Patellofemoral Ligament
      Imbrication for Genu Valgum with Lateral Patellar Instability.
AB  - A varus-producing distal femoral osteotomy (DFO) is an effective technique for
      the treatment of lateral patellar instability (LPI) in patients with concomitant
      moderate to severe valgus malalignment. Patellar maltracking and subluxation are
      corrected via neutralization of some of the laterally directed forces on the
      patella due to the valgus deformity. This can be accomplished with a distal
      femoral lateral opening-wedge or medial closing-wedge osteotomy and medial soft
      tissue stabilization. A medial closing-wedge osteotomy offers the advantages of
      immediate weight bearing and a single incision in cases requiring patellofemoral
      soft tissue stabilization. In this article, we describe our preferred operative
      technique for a medial closing-wedge DFO using a femoral locking plate and medial
      patellofemoral ligament imbrication for the correction of LPI.

PMID- 29349002
TI  - Medial Patellofemoral Ligament Reconstruction Using Dual Patella Docking
      Technique.
AB  - Medial patellofemoral ligament (MPFL) injuries are common in children and young
      adults. In patients with recurrent patellar dislocations with normal lower
      extremity alignment, anatomic reconstruction of the MPFL has been shown to
      restore patellar stability. We describe a technique that creates an anatomic
      reconstruction using a dual docking technique into the patella. Our technique is
      simple and efficacious for reconstructing the MPFL without implant fixation in
      the patella, allowing a maximal bone-tendon interface for healing.

PMID- 29349003
TI  - Arthroscopic Anterior Shoulder Stabilization With Incorporation of a Comminuted
      Bony Bankart Lesion.
AB  - Bony Bankart lesions are a common finding in patients with anterior glenohumeral
      dislocation. Although there are no defined guidelines, small bony Bankart
      fractures are typically treated arthroscopically with suture anchors. The 2 main
      techniques used are double- and single-row suture anchor stabilization, with
      debate over superiority. Biomechanical studies have shown improved reduction and
      stabilization with the double-row over the single-row suture anchor technique;
      however, this has not been reported for small or comminuted bony fragments. Both
      techniques have shown promising preliminary clinical outcomes. In this Technical
      Note, we describe our preferred technique for arthroscopic instability repair
      using a single-row all-suture anchor method with the incorporation of a
      comminuted bony Bankart fragment in the lateral decubitus position.

PMID- 29349004
TI  - Arthroscopic Treatment of a Malunion of a Posteromedial Tubercle Fracture of the
      Talus.
AB  - Posteromedial ankle impingement is rare and uncommonly associated with a
      fracture. Bone resection of the fragment is the recommended treatment. In this
      report, we describe the step-by-step surgical technique of arthroscopic resection
      of a malunion of a posteromedial talus fracture to correct the impingement.

PMID- 29349005
TI  - Arthroscopic Elbow Osteocapsular Arthroplasty.
AB  - Treatment of primary elbow osteoarthritis in the young active patient less than
      50 years old presents a treatment challenge to the practicing orthopaedic
      surgeon. Following failure of nonoperative management, surgical goals are aimed
      at reducing pain and improving joint mobility from bony impingement. Arthroscopic
      osteocapsular arthroplasty is a viable treatment option with few post-operative
      limitations. In contrast, total elbow arthroplasty is considered a salvage option
      in this patient population given the activity restrictions imposed. Osteocapsular
      arthroplasty combines soft tissue and bony debridement, osteophyte/loose body
      removal, synovectomy, capsular release, and bony contouring of the humerus and
      ulna to allow impingement-free range of motion.

PMID- 29349006
TI  - Simultaneous Bilateral Knee Valgus Stress Radiographic Technique.
AB  - The medial collateral ligament is the most commonly injured knee ligament. Valgus
      stress radiographs are reported to be an effective way to quantify the medial
      compartment opening. However, most of the techniques require the presence of a
      physician in the radiograph room to apply a manual valgus stress force, and can
      only be performed in 1 knee at a time. These techniques, although extremely
      effective, increase radiation exposure to physicians, are time consuming, and
      require additional radiographs to compare the side-to-side difference. The
      purpose of this Technical Note is to describe our preferred valgus stress
      radiographic technique to evaluate medial side laxity, which offers several
      advantages compared with conventional manual techniques.

PMID- 29349007
TI  - Anterior Cruciate Ligament Primary Repair With Independent Tensioning of the
      Anteromedial and Posterolateral Bundles.
AB  - This procedure represents an update on traditional primary repair methods by
      taking advantage of technological advancements to optimize soft tissue fixation
      and allow for an anatomic double-bundle primary repair with independent bundle
      tensioning and an internal brace construct to restore normal anterior cruciate
      ligament biomechanics.

PMID- 29349008
TI  - Meniscal Allograft Transplantation Made Simple: Bridge and Slot Technique.
AB  - Over recent years, appreciation for the critical role of the meniscus in joint
      biomechanics has led to an emphasis on meniscal preservation. Meniscal allograft
      transplant (MAT) is a promising biological solution for the symptomatic young
      patient with a meniscus-deficient knee that has not developed advanced
      osteoarthritis. As surgical techniques are refined and outcomes continue to
      improve, it is vital to consider the utility of such procedures and offer a
      straightforward approach to MAT. This article and accompanying video provide a
      step-by-step tutorial on how to perform a MAT using the bridge and slot
      technique, its key pearls and pitfalls as well as the relevant advantages and
      disadvantages of MAT.

PMID- 29349009
TI  - Arthroscopic Repair of Type II SLAP Tears Using Suture Anchor Technique.
AB  - Arthroscopic SLAP tear repair has become an increasingly used treatment for
      patients presenting with symptomatic SLAP tears after failed nonoperative
      management. Debridement, SLAP repair, and open or arthroscopic biceps tenodesis
      or tenotomy have been used for the treatment of SLAP tears. Various techniques
      for repair have been described, and furthermore, there is a high incidence of
      concomitant pathology of the shoulder. Repair remains an excellent option in
      isolated SLAP tears amenable to repair, with excellent outcomes in well-indicated
      patients. We present a method for repairing a SLAP tear using standard suture
      anchor fixation, anterior and posterior portals, and an accessory portal of
      Wilmington. Adequate labral repair can be achieved with this technique in
      patients with no concomitant biceps pathology. This report highlights this
      technique for SLAP repair in patients with isolated symptomatic SLAP tears that
      have failed conservative management.

PMID- 29349010
TI  - Arthroscopic Repair of Hip Labrum With Suture Anchors.
AB  - The acetabular labrum and the transverse acetabular ligament form a continuous
      ring of tissue on the periphery of the acetabulum that provides a seal for the
      hip joint and increases the surface area to spread load distribution during
      weight-bearing. When a labral tear is suspected, the treatment algorithm always
      begins with conservative management, including physical therapy and nonsteroidal
      anti-inflammatory drugs. When conservative management fails, patients become
      candidates for arthroscopic labral repair. In the last 2 decades, the rate of hip
      arthroscopy has increased nearly 4-fold. However, as hip arthroscopy is performed
      more frequently, there is a need for a proper technique to minimize morbidity,
      because hip arthroscopy has been known to have a steep learning curve. We present
      a method for arthroscopic hip labral repair using suture anchors without a
      capsular repair. This Technical Note highlights our technique for labral repair,
      along with pearls and pitfalls of hip arthroscopy.

PMID- 29349011
TI  - Middle Glenohumeral Ligament Abrasion Causing Upper Subscapularis Tear.
AB  - The middle glenohumeral ligament (MGHL) typically contributes partially to the
      anterior stability of the shoulder. In a very limited number of cases, the MGHL
      can cause abrasion on the upper edge of the subscapularis causing persistent pain
      symptoms for patients. The condition is exacerbated by internal rotation of the
      arm. In this Technical Note, we describe this entity and call it the SAM lesion
      (Subscapularis Abrasion from the MGHL). We present a technique of addressing this
      lesion.

PMID- 29349012
TI  - Arthroscopic Reduction and Internal Fixation of a Rim Fracture.
AB  - Femoroacetabular impingement is uncommonly associated to a rim fracture. Complete
      resection of the fragment might result in iatrogenic instability or poor femoral
      head coverage. In this report, we describe the step-by-step surgical technique of
      arthroscopic partial resection of a rim fracture, reduction and internal fixation
      of the remaining fragment to correct the impingement, and preserve the adequate
      acetabular coverage.

PMID- 29349013
TI  - Open-Wedge Valgus High Tibial Osteotomy Technique With Inverted L-Shaped
      Configuration.
AB  - High tibial osteotomy (HTO) is a useful alternative in the treatment of
      symptomatic varus malalignment. However, among its drawbacks is the tendency to
      decrease patellar height and increase the posterior tibial slope. The increased
      tibial slope increases anterior cruciate ligament tension and may compromise its
      function. On the other hand, patella baja often causes anterior knee pain and,
      over time, may favor degeneration of the patellofemoral joint. The aim of this
      study is to describe a technical modification of the standard open-wedge HTO. It
      consists of a double inverted L-shaped cut, which includes the anterior tibial
      tuberosity in the proximal fragment, to avoid any alteration of patellar height
      and control the eventual increase of the posterior tibial slope.

PMID- 29349014
TI  - Graft Preparation Technique to Optimize Hamstring Graft Diameter for Anterior
      Cruciate Ligament Reconstruction.
AB  - Hamstring autografts are frequently used for anterior cruciate ligament
      reconstruction. The inherent variability in graft diameter has been stated as a
      disadvantage in its use because the presence of smaller graft diameters has been
      correlated with increased risk of re-rupture. Several techniques have been
      described to address this concern. Modifications of the basic Graftlink technique
      allows for increased control over final graft diameter using a standard harvest
      of the semitendinosus tendon with or without the gracilis tendon, and results in
      a graft of adequate length and diameter in all patients with rigid cortical
      fixation on the femur and tibia.

PMID- 29349015
TI  - Patellar Tendon Repair With Ipsilateral Semitendinosus Autograft Augmentation.
AB  - Patellar tendon ruptures are rare but potentially devastating injuries. Acute
      repair after patellar tendon rupture affords the best opportunity for tension
      free restoration of the extensor mechanism. Biological augmentation of primary
      repair is believed to decrease strain across the repair site and reduce the risk
      of rerupture. We present a technique for primary patellar tendon repair with
      bidirectional fixation using transosseous tunnels, suture anchor fixation, and
      ipsilateral hamstring autograft augmentation in a distal patellar pole socket.

PMID- 29349016
TI  - The External Rotation Radiographic Technique for Posterolateral Injury.
AB  - Posterolateral corner injuries are a severe and often unrecognized pathology.
      Injuries to these structures are difficult to identify using magnetic resonance
      images. Physical examination tests including the dial test, frog-leg test, and
      varus stress test can be difficult to perform. In addition it is difficult to
      correctly evaluate the results in a multiligament injury setting. The correct
      diagnosis of this pathology is essential to determine the proper treatment and
      improve outcomes. Furthermore, failure to recognize this pathology is associated
      with a high risk of failure following isolated anterior cruciate ligament
      reconstructions. The purpose of this Technical Note is to present an alternative
      method for the evaluation of posterolateral corner injuries using radiographic
      images.

PMID- 29349017
TI  - Simultaneous Radiographic Technique to Evaluate Ankle Instability.
AB  - The use of ankle stress radiographs is common to evaluate ankle instability.
      However, the majority of the studies report the use of a manual method to apply
      the stress, increasing radiation exposure to the physician. Furthermore, as
      reported in other studies, the force applied during the stress may vary between
      examiners according the strength and experience. In this Technical Note, we
      describe our preferred method to evaluate ankle instability, either using an
      inversion or eversion stress, avoiding the necessity of a physician in the
      radiographic room.

PMID- 29349018
TI  - Open 4-Compartment Fasciotomy for Chronic Exertional Compartment Syndrome of the
      Leg.
AB  - Chronic exertional compartment syndrome (CECS) is a significant source of lower
      extremity pain and morbidity in the athletic population. Although endoscopic
      techniques have been introduced, open fasciotomy remains the mainstay of surgical
      treatment because of the paucity of evidence in support of an endoscopic
      approach. The literature on surgical management of CECS is mixed, and overall
      success rates are modest at best. Optimizing surgical technique, including
      prevention of neurovascular injury and wound complications, can make a
      significant impact on the clinical outcome. Here we present our surgical
      technique, including pearls and pitfalls, for open 4-compartment fasciotomy for
      treatment of chronic exertional compartment syndrome.

PMID- 29349019
TI  - Arthroscopic Decompression of Greater Trochanteric Sciatic Nerve Impingement.
AB  - Therapeutic extra-articular hip endoscopy is an effective treatment of greater
      trochanteric sciatic nerve impingement. We describe in detail technical pearls of
      the procedure including positioning, portal placement, and steps to obtaining
      adequate decompression while avoiding iatrogenic nerve injury.

PMID- 29349020
TI  - An Arthroscopic Humeral Medializing Repair of the Supraspinatus.
AB  - Posterosuperior repair of the rotator cuff is one of the most frequently
      performed surgical procedures in the shoulder. Its aim is to fix the tendon back
      to the bone to restore anatomy, improve shoulder function, and prevent
      progression of cuff tear arthropathy and attendant muscle degeneration. Despite
      technical advances in this procedure, in some cases, the tendon cannot be fixed
      back to the footprint without excessive tension on the repair. In young patients
      or in patients with low-grade muscle atrophy and fatty degeneration (Goutallier
      grade 1 or 2), it is mandatory to attempt fixation of the tendon to restore
      functional anatomy and prevent further muscle degeneration. In such cases, an
      arthroscopic medialized reinsertion of the supraspinatus may be considered. We
      describe an arthroscopic humeral medializing repair of the supraspinatus tendon
      that allows for a tension-free repair of the supraspinatus using common portals
      and instruments. The goal of this technique is to obtain tendon healing, restore
      functional anatomy, and prevent atrophy and fatty degeneration of the muscles of
      the rotator cuff.

PMID- 29349021
TI  - Arthroscopic Repair of Medial Transtendinous Rotator Cuff Tears.
AB  - Rotator cuff tears are extremely common in the adult population, and medial
      transtendinous rotator cuff tears, although rare, have recently been reported in
      the literature. These tears are almost always traumatic, which is a common
      indication for surgical management. It is necessary to consider these tears as a
      distinct subset when planning for rotator cuff repair because traditional repair
      techniques would overtension the tendon, increasing the risk for failure of the
      repair. The objective of this Technical Note is to describe an arthroscopic
      repair technique for these tears that avoids overtensioning the rotator cuff
      while still using repair techniques that are familiar to the arthroscopic
      shoulder surgeon.

PMID- 29349022
TI  - Arthroscopic Delivery of Injectable Bone Graft for Staged Revision Anterior
      Cruciate Ligament Reconstruction.
AB  - Bone defects caused by femoral and tibial tunnel enlargement can pose a
      significant technical challenge when planning to perform revision anterior
      cruciate ligament reconstruction. A number of options have been described for
      managing osseous deficiencies, including the use of large autograft or allograft
      bone dowels to provide sufficient tunnel fill and subsequent structural support
      for revision surgery. These techniques can be time-consuming and technically
      demanding to ensure proper tunnel fill and press-fit stability of the bone graft.
      We describe our preferred technique for arthroscopic bone grafting using a
      mixture of demineralized cortical bone graft augmented with platelet-rich plasma
      delivered through a simple delivery system.

PMID- 29349023
TI  - Bipolar Acromioclavicular Joint Resection.
AB  - Acromioclavicular (AC) joint arthropathy remains one of the most common causes of
      shoulder pain. In the case of AC joint arthropathy resistant to conservative
      treatment, most authors have recognized distal clavicle resection as the gold
      standard treatment. However, some challenges remain to be solved. One is the
      difficulty in visualization of the superior and posterior part of the distal
      clavicle from the midlateral portal, causing an incomplete resection of the
      distal clavicle. This could potentially lead to unresolved pain and therefore
      surgical failure. We propose a technique for arthroscopic resection of the distal
      clavicle and the medial portion of the acromion, without any added portal:
      bipolar AC joint resection. The term "bipolar" is used because both the acromion
      and the clavicle are resected, without injuring the superior capsule.

PMID- 29349024
TI  - The Crossing Internal Suture Augmentation Technique to Protect the All-Inside
      Anterior Cruciate Ligament Reconstruction Graft.
AB  - The crossing internal suture augmentation technique is an all-inside technique of
      anterior cruciate ligament reconstruction with augmentation of the hamstring
      tendon autograft with a braided ultrahigh-molecular-weight polyester-polyethylene
      suture tape resting on the adjustable cortical buttons on both the femoral and
      tibial sides. The internal suture augmentation acts as a backbone supporting and
      protecting the graft until the process of healing and ligamentization of the
      graft is completed. The ends of the suture tape are tied on the tibial button and
      additionally fixed to the tibia with a knotless anchor as a backup fixation with
      the knee in full extension. The technique has the advantages of being minimally
      invasive with small incisions and allowing preservation of the bone stock through
      the use of sockets. It also allows early return to activity thanks to the more
      secure rehabilitation and prevents early failure and stretching of the graft.

PMID- 29349025
TI  - Anterior Capsule Reconstruction for Irreparable Subscapularis Tears.
AB  - A subscapularis complete tear presents its own challenges in management. The
      glenohumeral biomechanics and force couple are reliant on a competent and
      functioning subscapularis muscle. An irreparable subscapularis makes those same
      challenges even more difficult to address. Traditionally, this problem has been
      addressed with tendon transfers, including pectoralis major or latissimus dorsi.
      These techniques can alter the ideal biomechanics of the shoulder and have high
      rates or failure. Iliotibial autograft or tibialis anterior have also been
      wrought with high failure rates. Recently, the superior capsular reconstruction
      has been described for irreparable tears of the supraspinatus and infraspinatus.
      Theoretically, this procedure can act as a check rein against subluxation, and
      may serve to reconnect the force couples of the rotator cuff. Anterior escape may
      represent a similar challenge when the irreparable rotator cuff tendon is the
      subscapularis. To address this, we describe an open anterior capsule
      reconstruction technique with an acellular dermal graft. We theorize that this
      procedure may serve in a similar capacity to its superior capsular counterpart.

PMID- 29349026
TI  - Arthroscopic Management of Posterior Instability due to "Floating" Posterior
      Inferior Glenohumeral Ligament Lesions.
AB  - The "floating" posterior inferior glenohumeral ligament (floating PIGHL) is an
      uncommon cause of posterior shoulder instability. This pathologic lesion, defined
      as detachment of both the origin of the PIGHL (posterior Bankart lesion) and
      insertion of the of the PIGHL from its humeral head insertion site, often results
      in significant and persistent shoulder instability symptoms. An effective
      surgical technique for arthroscopic repair of a floating PIGHL lesion is
      described and demonstrated.

PMID- 29349027
TI  - Arthroscopic Repair of Massive Subscapularis and Supraspinatus Tear by Double-Row
      Knotless Technique.
AB  - Subscapularis is the most powerful muscle in the rotator cuff. A steep learning
      curve and constrained space anteriorly make the repair difficult. In massive
      tears of the rotator cuff, repair of the subscapularis initially makes the
      massive supraspinatus tear repairable. We present our technique to repair
      subscapularis and supraspinatus tear by double-row anchors in a knotless and
      tension-free manner. This technique can be done in partial or full-thickness
      tears of the upper subscapularis.

PMID- 29349028
TI  - Knotless Suture Bridge Technique in High-Grade Bursal-Sided Rotator Cuff Tears.
      Is This The Way Forward?
AB  - We present our technique in managing high-grade bursal-sided rotator cuff tears.
      In this technique, the remaining intact cuff tissue is not sacrificed. The suture
      bridge technique is used to uniformly tension the torn tissue to the rotator cuff
      footprint. No knots are tied on the rotator cuff to minimize the tension on the
      cuff. The sutures are then anchored on the lateral cortex of the humerus. This
      technique allows repair with minimum tension while preserving the original length
      of the rotator cuff.

PMID- 29349029
TI  - Puncture Capsulotomy During Hip Arthroscopy for Femoroacetabular Impingement:
      Preserving Anatomy and Biomechanics.
AB  - We describe an arthroscopic technique for the treatment of labral pathology and
      femoroacetabular impingement that provides excellent access to the central and
      peripheral compartments while preserving the biomechanically crucial components
      of hip joint stability. The hip capsule and the ligaments within it have been
      shown to be integral to hip biomechanical stability. Other popular techniques
      such as interportal and T-capsulotomy inherently damage the capsuloligamentous
      complex of the hip and can be associated with postoperative gross instability,
      micro-instability, heterotopic ossification, and seroma. Capsular closure may
      mitigate some of these effects but has been associated with capsular
      insufficiency and requires postoperative restrictions that can be prolonged. Our
      surgical technique focuses on careful portal placement, replacement when
      necessary, use of a switching stick to maximize peripheral compartment
      visualization, and joint access in the most minimally invasive manner while
      avoiding complications associated with extended capsulotomy. The objective of
      this Technical Note is to describe a technique by which full access to the joint
      can be obtained while not disrupting the biomechanics of the joint capsule.

PMID- 29349030
TI  - Augmentation of Patellar Tendon Repair With Autologous Semitendinosus Graft-Porto
      Technique.
AB  - Patellar tendon ruptures can lead to significant functional deficiency of the
      extensor mechanism of the knee. These injuries, because of their inherent nature
      and associated complications, may require a complex treatment and remains a
      challenge for orthopaedic surgeons. Current surgical techniques present
      significant complications, including patellar fracture, damage to patellar
      articular cartilage, and abnormal patella height. This note describes a surgical
      technique to provide an additional reinforcement to the patellar tendon repair
      with a semitendinous autograft, without the necessity to perform any transosseous
      tunnels at the patella bone. First, the patellar tendon is repaired with an end
      to-end technique and the semitendinous tendon is harvested. A transosseous tunnel
      at the tibial tubercle is drilled and 2 rents are made, both medial and lateral
      to the retinaculum at the level of the intermedial segment of the patella close
      to the patellar margin. The graft is passed through the tunnel and rents in a U
      shaped form. The graft is sutured along the length of the patellar tendon on both
      margins in tension at 30 degrees  of knee flexion. Fluoroscopy imaging is
      performed to assess the patella height. This technique provides a significant
      augmentation of patellar tendon, avoiding the potential patella bone tunnel
      complications.

PMID- 29349031
TI  - Modified Elmslie-Trillat Procedure for Distal Realignment of Patella Tendon.
AB  - Patellofemoral dysfunction, due to either a patellofemoral malalignment or
      patellar instability, is a complex and debilitating condition that significantly
      decreases the knee function. Conservative management may yield significant
      clinical outcomes; however, when morphologic anomalies are identified, the
      surgical approach should be employed. Hence, several surgical procedures have
      been described in the scientific literature aiming the correction of underlying
      extensor mechanism malalignments. Still, the rate of complications is higher than
      desirable. The described technique is based on the principles of transferring the
      tibial tubercle medially as described in the Elmslie-Trillat technique. However,
      a curvilinear horizontal cut is made prior to the vertical cut, which raises a
      thick osseous fragment and allows the formation of a gutter when the osseous
      fragment is moved medially. Whereas the horizontal gutter provides stability to
      the bone fragment, the thicker dimension of the osseous fragment and retention of
      the distal attachment significantly enhances the osteotomy union. Hence, adequate
      pain relief and stability with very low postoperative morbidity could be
      achieved. The purpose of this surgical note is to describe a modification to the
      Elmslie-Trillat technique to treat patellofemoral dysfunctions, achieving a
      higher osseous stability and decreased postoperative morbidity.

PMID- 29349032
TI  - Revision Acromioclavicular-Coracoclavicular Reconstruction: Use of Precontoured
      Button and 2 Allografts.
AB  - Injuries to the acromioclavicular (AC) joint are common, particularly in the
      young and active population. Approximately 9% of all shoulder girdle injuries
      involve the AC joint, and AC joint dislocations represent approximately 8% of all
      joint dislocations throughout the body. AC joint injuries are graded as type I
      through type VI according to the Rockwood classification. Type I and II injuries
      are typically treated nonoperatively, whereas type IV, V, and VI injuries are
      most often treated surgically. A variety of surgical techniques have been
      described, including anatomic and nonanatomic reconstruction. However, up to 80%
      of patients go on to lose radiographic reduction, and between 20% and 30% have
      complications leading to reoperation. Therefore, the objective of this Technical
      Note is to describe our preferred technique for the treatment of AC joint
      instability in the revision setting. This technique uses a Dog Bone Button
      (Arthrex, Naples, FL) and 2 allografts.

PMID- 29349033
TI  - Arthroscopic Reduction and Fixation of Tibial Spine Avulsion Fractures by a
      Stainless Steel Wiring Technique.
AB  - Several techniques of arthroscopic treatment of tibial spine avulsion fractures
      have been described in the literature. These techniques include the use of
      various fixation devices such as screws, K-wires, wiring, sutures, and suture
      anchors. In this study, we evaluate a new wiring technique for the treatment of
      these injuries. This technique involves fixation by stainless steel tension wires
      passed over the fractured spine and tied over a bone bridge. The advantages of
      this technique are that it aids in reduction, allows for compression of the
      tibial spine fragment anatomically in its fracture bed, provides stable fixation
      in difficult comminuted fractures, and allows for early mobilization and weight
      bearing because of the solid fixation.

PMID- 29349034
TI  - Arthroscopic Microfracture of Hip Chondral Lesions.
AB  - Microfracture of hip chondral lesions has been performed for more than a decade
      with modified treatment principles and techniques from knee arthroscopy. This
      note and accompanying video review the pertinent techniques, pearls, and pitfalls
      of the microfracture procedure in the treatment of hip chondral lesions. After
      debridement of damaged chondral tissue, the size of the lesion is approximated to
      determine the number of microfracture holes to create. The working portal may be
      adjusted based on the site of the lesion. Microfracture picks of different angles
      are used to ensure perpendicular advancement to a depth of 3 to 4 mm in the
      subchondral bone. The holes are placed at a gap of approximately 3 to 4 mm. The
      debris is washed out to obtain open holes connecting the marrow with the
      articular surface. The microfracture procedure should be performed near the end
      of the overall procedure to secure the bleeding bone marrow within the joint and
      prevent washout.

PMID- 29349035
TI  - Successful treatment of a patient with chyluria due to lymphangioleiomyomatosis
      using sirolimus.
AB  - Lymphangioleiomyomatosis (LAM) is a rare and progressive neoplastic disease of
      young woman, characterized by the proliferation of abnormal smooth muscle-like
      cells (LAM cells) in the lungs and axial lymphatics. A 44-year-old woman was
      referred to our hospital because pleural effusion was detected during a health
      checkup. She had chylothorax, chylous ascites, and chyluria, and her computed
      tomography scan showed a solid tumor in the pelvis. Surgical biopsy was
      performed; she was diagnosed as having LAM. We could not control the fluid
      collection and chyluria using standard medical treatments. Therefore, we chose to
      administer sirolimus, and her symptoms dramatically improved. The mechanism of
      chyluria presumably involved LAM cell infiltrates in the ureter via the lymphatic
      vessel flow, which causes LAM to develop because of ureter wall exposure.

PMID- 29349036
TI  - Alternative topical anesthesia for bronchoscopy in a case of severe lidocaine
      allergy.
AB  - Lidocaine allergy presents a unique difficulty for both patients and providers
      who undergo/perform bronchoscopy. We present a case of a 73 yo male with severe
      lidocaine allergy who successfully underwent bronchoscopy with chloroprocaine
      topical anesthesia and discuss alternative topical anesthetic agents that may be
      used in this special situation.

PMID- 29349037
TI  - Family history of alcoholism and the human brain response to oral sucrose.
AB  - A heightened hedonic response to sweet tastes has been associated with increased
      alcohol preference and alcohol consumption in both humans and animals. The
      principal goal of this study was to examine blood oxygenation level dependent
      (BOLD) activation to high- and low-concentration sweet solutions in subjects who
      are either positive (FHP) or negative (FHN) for a family history of alcoholism.
      Seventy-four non-treatment seeking, community-recruited, healthy volunteers (22.8
      +/- 1.6 SD years; 43% men) rated a range of sucrose concentrations in a taste
      test and underwent functional magnetic resonance imaging (fMRI) during oral
      delivery of water, 0.83 M, and 0.10 M sucrose. Sucrose compared to water produced
      robust activation in primary gustatory cortex, ventral insula, amygdala, and
      ventral striatum. FHP subjects displayed greater bilateral amygdala activation
      than FHN subjects in the low sucrose concentration (0.10 M). In secondary
      analyses, the right amygdala response to the 0.10 M sucrose was greatest in FHP
      women. When accounting for group differences in drinks per week, the family
      history groups remained significantly different in their right amygdala response
      to 0.10 M sucrose. Our findings suggest that the brain response to oral sucrose
      differs with a family history of alcoholism, and that this response to a mildly
      reinforcing primary reward might be an endophenotypic marker of alcoholism risk.

PMID- 29349039
TI  - Engineering Escherichia coli for the production of terpene mixture enriched in
      caryophyllene and caryophyllene alcohol as potential aviation fuel compounds.
AB  - Recent studies have revealed that caryophyllene and its stereoisomers not only
      exhibit multiple biological activities but also have desired properties as
      renewable candidates for ground transportation and jet fuel applications. This
      study presents the first significant production of caryophyllene and caryolan-1
      ol by an engineered E. coli with heterologous expression of mevalonate pathway
      genes with a caryophyllene synthase and a caryolan-1-ol synthase. By optimizing
      metabolic flux and fermentation parameters, the engineered strains yielded 449
      mg/L of total terpene, including 406 mg/L sesquiterpene with 100 mg/L
      caryophyllene and 10 mg/L caryolan-1-ol. Furthermore, a marine microalgae
      hydrolysate was used as the sole carbon source for the production of
      caryophyllene and other terpene compounds. Under the optimal fermentation
      conditions, 360 mg/L of total terpene, 322 mg/L of sesquiterpene, and 75 mg/L
      caryophyllene were obtained from the pretreated algae hydrolysates. The highest
      yields achieved on the biomass basis were 48 mg total terpene/g algae and 10 mg
      caryophyllene/g algae and the caryophyllene yield is approximately ten times
      higher than that from plant tissues by solvent extraction. The study provides a
      sustainable alternative for production of caryophyllene and its alcohol from
      microalgae biomass as potential candidates for next generation aviation fuels.

PMID- 29349038
TI  - Abnormal neural hierarchy in processing of verbal information in patients with
      schizophrenia.
AB  - Previous research indicates abnormal comprehension of verbal information in
      patients with schizophrenia. Yet the neural mechanism underlying the breakdown of
      verbal information processing in schizophrenia is poorly understood. Imaging
      studies in healthy populations have shown a network of brain areas involved in
      hierarchical processing of verbal information over time. Here, we identified
      critical aspects of this hierarchy, examining patients with schizophrenia. Using
      functional magnetic resonance imaging, we examined various levels of information
      comprehension elicited by naturally presented verbal stimuli; from a set of
      randomly shuffled words to an intact story. Specifically, patients with first
      episode schizophrenia (N = 15), their non-manifesting siblings (N = 14) and
      healthy controls (N = 15) listened to a narrated story and randomly scrambled
      versions of it. To quantify the degree of dissimilarity between the groups, we
      adopted an inter-subject correlation (inter-SC) approach, which estimates
      differences in synchronization of neural responses within and between groups. The
      temporal topography found in healthy and siblings groups were consistent with our
      previous findings - high synchronization in responses from early sensory toward
      high order perceptual and cognitive areas. In patients with schizophrenia,
      stimuli with short and intermediate temporal scales evoked a typical pattern of
      reliable responses, whereas story condition (long temporal scale) revealed robust
      and widespread disruption of the inter-SCs. In addition, the more similar the
      neural activity of patients with schizophrenia was to the average response in the
      healthy group, the less severe the positive symptoms of the patients. Our
      findings suggest that system-level neural indication of abnormal verbal
      information processing in schizophrenia reflects disease manifestations.

PMID- 29349040
TI  - An unusual case of primary melioidotic prostatic abscess complicated by perianal
      abscess.
AB  - Burkholderia pseudomallei is recognized to cause severe and fatal infections.
      Most of the infections caused by this facultative intracellular gram-negative
      bacterium are pneumonia, soft tissue, genito-urinary and central nervous system
      infection. We report an unusual case of primary prostatic abscess complicated by
      perianal abscess caused by Burkholderia pseudomallei. Melioidosis related
      anorectal infections have not been previously reported in the literature.

PMID- 29349041
TI  - Unusual cause of severe diabetic ketoacidosis precipitated by Streptococcus
      bovis/equinus (SBSEC) bacteremia: Case report and review of literature.
AB  - Diabetic ketoacidosis is a feared complication in patients with diabetes mellitus
      and poses high risk of mortality and morbidity unless treated in timely manner.
      Infection is one of the most common precipitating factors for the development of
      diabetic ketoacidosis. Bacteremia with Group A and Group B beta hemolytic
      streptococcal strains are well known, however nonenterococcal Group D strains
      such as the Streptococcus bovis/Streptococcus equinus complex (SBSEC) still
      remains an understudied entity. Here we present a case of a 35-year-old Type I
      diabetic female presenting with severe diabetic ketoacidosis with overlapping
      features of hyperosmolar hyperglycemia, precipitated by Streptococcus
      alactolyticus bacteremia, successfully treated with four-week course of
      parenteral ceftriaxone. This case report emphasizes the potential importance of
      SBSEC as an emerging pathologic strain and culprit for triggering diabetic
      ketoacidosis which requires prompt diagnosis and targeted therapy.

PMID- 29349042
TI  - An optimized targeted Next-Generation Sequencing approach for sensitive detection
      of single nucleotide variants.
AB  - Monitoring of minimal residual disease (MRD) has become an important clinical
      aspect for early relapse detection during follow-up care after cancer treatment.
      Still, the sensitive detection of single base pair point mutations via Next
      Generation Sequencing (NGS) is hampered mainly due to high substitution error
      rates. We evaluated the use of NGS for the detection of low-level variants on an
      Ion Torrent PGM system. As a model case we used the c.1849G > T (p.Val617Phe)
      mutation of the JAK2-gene. Several reaction parameters (e.g. choice of DNA
      polymerase) were evaluated and a comprehensive analysis of substitution errors
      was performed. Using optimized conditions, we reliably detected JAK2 c.1849G > T
      VAFs in the range of 0.01-0.0015% which, in combination with results obtained
      from clinical data, validated the feasibility of NGS-based MRD detection.
      Particularly, PCR-induced transitions (mainly G > A and C > T) were the major
      source of error, which could be significantly reduced by the application of
      proofreading enzymes. The integration of NGS results for several common point
      mutations in various oncogenes (i.e. IDH1 and 2, c-KIT, DNMT3A, NRAS, KRAS, BRAF)
      revealed that the prevalent transition vs. transversion bias (3.57:1) has an
      impact on site-specific detection limits of low-level mutations. These results
      may help to select suitable markers for MRD detection and to identify individual
      cut-offs for detection and quantification.

PMID- 29349043
TI  - Vermicomposting and anaerobic digestion - viable alternative options for
      terrestrial weed management - A review.
AB  - The management of terrestrial weed is of great concern for the scientific
      community as these weeds cause adverse effect in different ecosystems like
      forest, agriculture and urban. The widespread of these weeds by their adaptive
      capability and morphological advancement is difficult to control. Parthenium
      hysterophorous, Lantana camara, Saccharum spontaneum, Ageratum conyzoides are the
      weeds that spread all over the world. There are various management practices
      employed for the control of this weeds. But all of these practices have some
      drawbacks those are neither environment friendly nor economical. In this paper a
      review has been done to evaluate various alternative management practices for
      these terrestrial weeds and to analyze their feasibility. Vermicomposting and
      anaerobic digestion can be viable alternative option which is cost effective as
      well. There are few studies regarding vermicomposting and anaerobic digestions of
      terrestrial weeds are done.

PMID- 29349044
TI  - Evaluating the effect of enzymatic pretreatment on the anaerobic digestibility of
      pulp and paper biosludge.
AB  - Anaerobic digestion of biosludge has not yet been implemented in pulp mills due
      to low biogas yields. Enzymatic pretreatment of biosludge has shown improvements
      in biogas yields but results are varied. A key limitation of previous studies is
      that they fail to consider the COD contribution from the enzyme solutions. The
      aim of this study was to systematically investigate the potential for enzymatic
      pretreatment on the anaerobic digestibility of pulp mill biosludge. Out of the
      six enzymes tested, four enhanced the anaerobic digestibility of biosludge. At
      the end of the BMP, a maximum improvement of 26% in biogas yield was observed
      with protease from B. licheniformis. There was no correlation between enzymatic
      activities on standard substrates and/or on biosludge and the effect of enzymes
      on biogas yields. Enzymes have potential for improving biosludge anaerobic
      digestibility but more research on optimal conditions and potential synergies
      with other pretreatment is needed.

PMID- 29349045
TI  - Advantages, Disadvantages, Indications, Contraindications and Surgical Technique
      of Laryngeal Airway Mask.
AB  - The beauty of the laryngeal mask is that it forms an air tight seal enclosing the
      larynx rather than plugging the pharynx, and avoid airway obstruction in the
      oropharynx. The goal of its development was to create an intermediate form of
      airway management face mask and endotracheal tube. Indication for its use
      includes any procedure that would normally involve the use of a face mask. The
      laryngeal mask airway was designed as a new concept in airway management and has
      been gaining a firm position in anesthetic practice. Despite wide spread use the
      definitive role of the laryngeal mask airway is yet to be established. In some
      situations, such as after failed tracheal intubation or in oral surgery its use
      is controversial. There are several unresolved issues, for example the effect of
      the laryngeal mask on regurgitation and whether or not cricoids pressure prevents
      placement of mask. We review the techniques of insertion, details of
      misplacement, and complications associated with use of the laryngeal mask. We
      then attempt to clarify the role of laryngeal mask in air way management during
      anesthesia, discussing the advantages and disadvantages as well as indications
      and contraindications of its use in oral and maxillofacial surgery.

PMID- 29349046
TI  - Reduction of Closed Frontal Sinus Fractures through Suprabrow Approach.
AB  - Background: The traditional approach for reduction of frontal sinus fractures is
      coronal incision. Inherent complications of the coronal approach include long
      scar, hair loss, and long operation time. We describe a simple approach for the
      reduction of frontal sinus anterior wall fractures using a suprabrow incision
      that is commonly used for brow lift. Methods: From March 2007 to October 2016,
      the authors identified patients with anterior wall frontal sinus fractures
      treated by open reduction through a suprabrow incision. Only cases with
      photographic/radiographic documentation and a minimum follow-up of 6 months were
      included. The incision line was designed to be at the upper margin of the
      eyebrow. Medical records and radiographic data were retrospectively reviewed.
      Surgical outcomes, cosmetic results, and complication were assessed. The patient
      scale of the patient and observer scar assessment scale was used to assess
      patient satisfaction for incisional scar at the 6-month follow-up. Results:
      Thirty-one patients underwent fracture reduction through a suprabrow approach
      during the study period, with a mean follow-up of 41 months. No patients showed
      any recurrent displacement, eyebrow asymmetry, or infection during follow-up.
      Thirteen patients reported their forehead paresthesia postoperatively, and 12 of
      them had preoperative symptom. One patient complained of incisional scar and
      underwent scar revision. All patients were satisfied with their eyebrow and
      forehead contour. Conclusion: The suprabrow approach allowed for an accurate
      reduction of the fractures in the anterior wall frontal sinus by providing direct
      visualization of the fracture. This transcutaneous approach can effectively
      restore forehead contour with acceptable postoperative complications and patient
      satisfaction.

PMID- 29349047
TI  - Reduction of the Isolated Anterior Wall of the Maxillary Sinus Fracture with
      Double Urinary Balloon Catheters and Fibrin Glue.
AB  - Background: Conservative treatment is performed for isolated anterior wall of the
      maxillary sinus fractures, in many cases when the fracture is clinically not
      severe and asymptomatic. Despite the absence of symptoms, complications such as
      sinusitis, rhinitis, and chronic purulent secretion may develop; therefore,
      successful reduction is required. We attempted to reduce the risk of
      complications using an alternative technique: reduction of the fracture with two
      urinary balloon catheters inserted through the maxillary ostium and fixation
      using fibrin glue, which minimizes the damage to the bony fragments and sinus
      mucosa. Methods: In this study, 38 patients who were diagnosed with an isolated
      anterior wall of the maxillary sinus fracture at our hospital between January
      2014 and January 2017 were enrolled. The fracture site was exposed via the
      Caldwell-Luc approach followed by reduction through the insertion of two urinary
      balloon catheters using a nasal endoscope and fixation with fibrin glue. The sex,
      cause of fracture, physical examination, and presence of complications were
      examined and patient's medical records and facial bone computed tomography scans
      were analyzed. Results: Radiological evaluation showed that there was no evidence
      of collapsed reduction fragments. Although some patients had remaining symptoms
      of hypoesthesia (15%; 3 patients), there were no complications such as infection,
      rhinitis, sinusitis, and chronic purulent secretion at the surgical site.
      Conclusion: In this study, we present an alternative surgical technique using two
      urinary balloon catheters and fibrin glue for the successful reconstruction of an
      isolated anterior wall of the maxillary sinus fracture. This technique enables
      precise restoration with a reduced risk of complications.

PMID- 29349048
TI  - Versatility of Modified Nasolabial Flap in Oral and Maxillofacial Surgery.
AB  - Background: To evaluate the versatility and reach of modified nasolabial flap
      used in reconstruction of defects created in and around the oral cavity. Methods:
      A total number of 20 cases were selected. Out of which 13 were males and 7
      females. The age of these patients ranged from 24-63 years. 29 modified
      nasolabial flaps were raised in twenty patients. Based on clinical and
      histopathological examination, out of 20 patients, 14 patients were diagnosed
      with oral submucous fibrosis, 3 with verrucous carcinoma, 1 with squamous
      papilloma, 1 with oro-antral fistula and 1 with traumatic loss of lower lip.
      Results: Minimum preoperative interincisal distance (IID) was 0 mm and maximum
      was 15 mm with mean of 6.00+/-4.76 mm in patients with oral submucous fibrosis
      and 12 months postoperatively minimum IID was 16 mm and maximum was 41 mm with
      mean of 28.00+/-8.96 mm. In one case, dehiscence (3.4%) was noted on the anterior
      tip for which tip revision was done. Bulky appearance of the flap intraorally was
      observed in 2 cases (6.9%). Five (17.2%) among the 29 flaps had visible scar at
      the donor site postoperatively up to 3 months. Conclusion: Numerous
      reconstructive techniques have been employed in the reconstruction of small to
      intermediate sized defects of oral cavity. Modified nasolabial flap is a
      versatile flap which has robust vascularity and can be successfully used with
      minimal complications. It can be rotated intraorally to extend from the soft
      palate to the lip. Thus, it can be used efficiently to treat the small defects of
      the oral cavity as well as recreating lost lip structure.

PMID- 29349049
TI  - The Reliability of the Transconjunctival Approach for Orbital Exposure:
      Measurement of Positional Changes in the Lower Eyelid.
AB  - Background: Lower eyelid incisions are widely used for the orbital approach in
      periorbital trauma and aesthetic surgery. In general, the subciliary approach is
      known to cause disposition of the lower eyelid by scarring the anterior lamella
      in some cases. On the other hand, many surgeons believe that a transconjunctival
      approach usually does not result in such complications and is a reliable method.
      We measured positional changes in the lower eyelid in blowout fracture repair
      since entropion is one of the most serious complications of the transconjunctival
      orbital approach. Methods: To measure the positional changes in the lower
      eyelids, we analyzed preoperative and postoperative photographs over various time
      intervals. In the analysis of the photographs, marginal reflex distance 2 (MRD2)
      and eyelash angle were used as an index of eyelid position. Statistical analyses
      were performed to identify the significance in the positional changes. All
      patients underwent orbital reconstruction through a transconjunctival incision by
      a single plastic surgeon. Results: In 42 blowout fracture patients, there was no
      statistical significant difference in the MRD2 and eyelash angle. Furthermore,
      there were no clinical complications, such as infection, hematoma, bleeding, or
      implant protrusion, during the follow-up periods. Conclusion: The advantages of
      the transconjunctival approach for orbital access include minimal scarring and a
      lower risk of eyelid displacement compared with other approaches. Based on these
      results, we recommend the transconjunctival approach for orbital exposure as a
      safe and reliable method.

PMID- 29349050
TI  - A Comparison of the Local Flap and Skin Graft by Location of Face in
      Reconstruction after Resection of Facial Skin Cancer.
AB  - Background: Surgery for reconstruction of defects after surgery should be
      performed selectively and the many points must be considered. The authors
      conducted this study to compare the local flap and skin graft by facial location
      in the reconstruction after resection of facial skin cancer. Methods: The authors
      performed the study in patients that had received treatment in Department of
      Plastic Surgery, Gyeongsang National University. The cases were analyzed
      according to the reconstruction methods for the defects after surgery, sex, age,
      tumor site, and tumor size. Additionally, the authors compared differences of
      aesthetic satisfaction (out of 5 points) of patients in the local flap and skin
      graft by facial location after resection of facial skin cancer by dividing the
      face into eight areas. Results: A total of 153 cases were confirmed. The most
      common facial skin cancer was basal cell carcinoma (56.8%, 87 cases), followed by
      squamous cell carcinoma (37.2%, 57 cases) and bowen's disease (5.8%, 9 cases).
      The most common reconstruction method was local flap 119 cases (77.7%), followed
      by skin graft 34 cases (22.3%). 86 patients answered the questionnaire and mean
      satisfaction of the local flap and skin graft were 4.3 and 3.5 (p=0.04),
      respectively, indicating that satisfaction of local flap was significantly high.
      Conclusion: When comparing satisfaction of patients according to results, local
      flap shows excellent effects in functional and cosmetic aspects would be able to
      provide excellent results rather than using a skin graft with poor touch and tone
      compared to the surrounding normal skin.

PMID- 29349051
TI  - Anisakiasis Involving the Oral Mucosa.
AB  - Anisakis is a parasite with life cycles involving fish and marine mammals. Human
      infection, anisakiasis, occurs with the ingestion of raw infected seafood and
      usually presents with acute or chronic gastrointestinal symptoms from esophageal
      or gastric invasion. We report a rare caseinvolving the oral cavity. A 39-year
      old male presented with oral and sub-sternal pain of one day duration after
      eating raw cuttlefish. Physical examination revealed areas of erythema and edema
      with a central white foreign particle on the labial and buccal mucosa. With
      microscopic field we could remove the foreign material from the lesions. The
      foreign material was confirmed to be Anisakis. Anisakis was also removed from the
      esophagus by esophagogastroduodenoscopy. The patient was discharged the following
      day without complication. Anisakiasis is frequently reported in Korea and Japan,
      countries where raw seafood ingestion is popular. The symptoms of acute
      anisakiasis include pain, nausea, and vomiting and usually begin 2-12 hours after
      ingestion. The differential diagnosis includes food poisoning, acute gastritis,
      and acute pancreatitis. A history of raw seafood ingestion is important to the
      diagnosis of anisakiasis. Treatment is complete removal of the Anisakis to
      relieve acute symptoms and prevent chronic granulomatous inflammation.

PMID- 29349052
TI  - Malar Relocation with Reverse-L Osteotomy and Autogenous Bone Graft.
AB  - The zygomaticomaxillary complex (ZMC) functions as a buttress for the face and is
      the cornerstone to a person's aesthetic appearance, by both setting the midfacial
      width and providing prominence to the cheek. Malar deficiency is often acquired
      by blunt injury incurred in a traumatic accident, resulting in ZMC fracture. A 48
      year-old male patient presented a right ZMC fracture after contusion injury by a
      baseball. He only received conservative management and later he suffered
      discomfort during mouth opening at the moment of mastication, due to trismus
      involving the temporomandibular joint. In the current case, we describe a
      surgical technique, by which the malar body is shifted anteriorly and laterally
      after combined oblique-vertical osteotomy. The technique presented, eventually
      restored the former aesthetic position of the malar complex and symmetry, and,
      moreover, improved mastication function.

PMID- 29349053
TI  - Myxoid Solitary Fibrous Tumor on the Scalp.
AB  - Myxoid solitary fibrous tumor (SFT) is very rare soft tissue neoplasm. It is
      microscopically composed of spindle cells which is individually separated by
      delicate band of collagen fibers. And this tumor cells are immunohisto
      chemistrically highlighted by CD34. Myxoid SFT has indolent clinical course and a
      good prognosis, so it is important to make a diagnosis because of its
      morphological similarities to myxoid spindle cell neoplasms that have different
      prognoses and treatment. We report the case of a 20-year-old female with a myxoid
      SFT found in the left temporo-parietal scalp. This case report appears to be the
      first reported scalp occurrence of this rare tumor.

PMID- 29349054
TI  - Post-Traumatic Peripheral Giant Osteoma in the Frontal Bone.
AB  - Osteomas are benign, slow-growing tumors that most frequently occur in the
      craniomaxillofacial region. These tumors are mostly asymptomatic and are
      generally found incidentally. A giant osteoma is generally considered to be
      greater than 30 mm in diameter or 110 g in weight. A 35-year-old female presented
      to us with complaints of a firm mass that showed continuous growth on the
      forehead following trauma. A hairline incision was made to expose the osteoma.
      Biopsy of the tumor confirmed a osteoma. There were no complications after
      surgery. Postoperative computed tomography revealed that the tumor was completely
      removed. Because a peripheral giant osteoma of the frontal bone with a history of
      trauma is a rare finding, thorough history-taking, physical examination, and
      preoperative imaging tests are needed for patients with a history of trauma to
      rule out a giant osteoma.

PMID- 29349055
TI  - Reconstruction of a Traumatic Cleft Earlobe Using a Combination of the Inverted V
      Shaped Excision Technique and Vertical Mattress Suture Method.
AB  - Traumatic cleft earlobes are a common problem encountered by plastic and
      reconstructive surgeons. Various techniques have been reported for the repair of
      traumatic cleft earlobes. Usually, the techniques of split earlobe repair are
      divided into two categories, namely straight- and broken-line repairs. Straight
      line repair is simple and easy, but scar contracture frequently results in
      notching of the inferior border of the lobule. It can be avoided by the broken
      line repair such as Z-plasty, L-plasty, or a V-shaped flap. Between April 2016
      and February 2017, six patients who presented with traumatic cleft earlobe
      underwent surgical correction using a combination of the inverted V-shaped
      excision technique and vertical mattress suture method. All the patients were
      female and had a unilateral complete cleft earlobe. No postoperative notching of
      the inferior border the lobule occurred during 6-16 months of follow-up. Without
      the use of a broken-line repair, both the patients and the operators attained
      aesthetically satisfactory results. Therefore, the combination of the inverted V
      shaped excision technique and vertical mattress suture method is considered
      useful in the treatment of traumatic cleft earlobes.

PMID- 29349056
TI  - Sinus Tract Formation with Chronic Inflammatory Cystic Mass after Beta Tricalcium
      Phosphate Insertion.
AB  - Beta tricalcium phosphate (beta-TCP) is one of allogenic bone substitute which is
      known to have interconnected pores that draws cell and nutrients for bone
      generation. It has been resulted in good outcomes for bone defect coverage or
      augmentation. However, several studies have also reported negative outcomes and
      associated complications including unexpected formation of cystic mass,
      continuous pain and secretion. We present the case of a 36-year-old man with a
      right cheek cystic mass who had a history of right zygomaticomaxillary (ZM)
      complex fracture and surgical correction with beta-TCP powder insertion to ZM
      bone defect. Excisional biopsy under local anesthesia revealed calcified mass in
      a sinus tract which was found to be connected to the ZM bone defect site in
      postoperative computed tomography image. Further excision under general
      anesthesia was performed to remove the sinus tract and fine granules which filled
      the original defect site. Pathologic report revealed bony spicules and
      calcification materials with chronic foreign body reaction. Postoperative
      complications and recurrence were not reported.

PMID- 29349057
TI  - Ectopic Preauricular Sinus in a Facial Cleft and Microtia Patient.
AB  - Preauricular sinus is a congenital malformation that is very commonly encountered
      among the general population and it has especially high prevalence among Asians
      when compared to other ethnic groups. It can often go unnoticed or easily
      overlooked by the patient or even by doctors because most of them are
      asymptomatic and is most of the time only a tiny pit that can be trivial in terms
      of aesthetics. We report a very rare and unique case that has no precedence what
      so ever; hence no reported case in the literature: an ectopic preauricular sinus
      in a facial cleft and microsomia patient.

PMID- 29349058
TI  - Rhabdomyomatous Mesenchymal Hamartoma Presenting as a Midline Mass on a Chin.
AB  - A 17-month-old boy was evaluated for a midline mass on his chin. The mass was
      anchored to the mentalis muscle with a stalk-like structure. The pathological
      diagnosis of the mass was rhabdomyomatous mesenchymal hamartoma. This is the
      first report of rhabdomyomatous mesenchymal hamartoma presenting as a midline
      chin mass in Korean pediatric patients.

PMID- 29349059
TI  - Dear Members of the Association.

PMID- 29349060
TI  - Sost Deficiency does not Alter Bone's Lacunar or Vascular Porosity in Mice.
AB  - SCLEROSTIN (Sost) is expressed predominantly in osteocytes acting as a negative
      regulator of bone formation. In humans, mutations in the SOST gene lead to
      skeletal overgrowth and increased bone mineral density, suggesting that
      SCLEROSTIN is a key regulator of bone mass. The function of SCLEROSTIN as an
      inhibitor of bone formation is further supported by Sost knockout (KO) mice which
      display a high bone mass with elevated bone formation. Previous studies have
      indicated that Sost exerts its effect on bone formation through Wnt-mediated
      regulation of osteoblast differentiation, proliferation, and activity. Recent in
      vitro studies have also suggested that SCLEROSTIN regulates angiogenesis and
      osteoblast-to-osteocyte transition. Despite this wealth of knowledge of the
      mechanisms responsible for SCLEROSTIN action, no previous studies have examined
      whether SCLEROSTIN regulates osteocyte and vascular configuration in cortices of
      mouse tibia. Herein, we image tibiae from Sost KO mice and their wild-type (WT)
      counterparts with high-resolution CT to examine whether lack of SCLEROSTIN
      influences the morphometric properties of lacunae and vascular canal porosity
      relating to osteocytes and vessels within cortical bone. Male Sost KO and WT mice
      (n = 6/group) were sacrificed at 12 weeks of age. Fixed tibiae were analyzed
      using microCT to examine cortical bone mass and architecture. Then, samples were
      imaged by using benchtop and synchrotron nano-computed tomography at the
      tibiofibular junction. Our data, consistent with previous studies show that, Sost
      deficiency leads to significant enhancement of bone mass by cortical thickening
      and bigger cross-sectional area and we find that this occurs without
      modifications of tibial ellipticity, a measure of bone shape. In addition, our
      data show that there are no significant differences in any lacunar or vascular
      morphometric or geometric parameters between Sost KO mouse tibia and WT
      counterparts. We, therefore, conclude that the significant increases in bone mass
      induced by Sost deficiency are not accompanied by any significant modification in
      the density, organization, or shape of osteocyte lacunae or vascular content
      within the cortical bone. These data may imply that SCLEROSTIN does not modify
      the frequency of osteocytogenic recruitment of osteoblasts to initiate terminal
      osteocytic differentiation in mice.

PMID- 29349061
TI  - Self-Reported Adverse Drug Reactions, Medication Adherence, and Clinical Outcomes
      among Major Depressive Disorder Patients in Ethiopia: A Prospective Hospital
      Based Study.
AB  - Background: There is paucity of data on prevalence of Adverse Drug Reactions
      (ADRs) and adherence and clinical outcomes of antidepressants. The present study
      determined the magnitude of ADRs of antidepressants and their impact on the level
      of adherence and clinical outcome. Methods: A prospective cross-sectional study
      was conducted among depression patients from September 2016 to January 2017 at
      Gondar University Hospital psychiatry clinic. The Naranjo ADR probability scale
      was employed to assess the ADRs. The rate of medication adherence was determined
      using Morisky Medication Adherence Measurement Scale-Eight. Results: Two hundred
      seventeen patients participated in the study, more than half of them being males
      (122; 56.2%). More than one-half of the subjects had low adherence to their
      medications (124; 57.1%) and about 186 (85.7%) of the patients encountered ADR.
      The most common ADR was weight gain (29; 13.2%). More than one-half (125; 57.6%)
      of the respondents showed improved clinical outcome. Optimal level of medication
      adherence decreased the likelihood of poor clinical outcome by 56.8%. Conclusion:
      ADRs were more prevalent. However, adherence to medications was very poor in the
      setup. Long duration of depression negatively affects the rate of adherence. In
      addition, adherence was found to influence the clinical outcome of depression
      patients.

PMID- 29349063
TI  - Abdominal Manual Therapy Repairs Interstitial Cells of Cajal and Increases
      Colonic c-Kit Expression When Treating Bowel Dysfunction after Spinal Cord
      Injury.
AB  - Background: This study aimed to evaluate the therapeutic effects of abdominal
      manual therapy (AMT) on bowel dysfunction after spinal cord injury (SCI),
      investigating interstitial cells of Cajal (ICCs) and related c-kit expression.
      Methods: Model rats were divided as SCI and SCI with drug treatment (intragastric
      mosapride), low-intensity (SCI + LMT; 50 g, 50 times/min), and high-intensity AMT
      (SCI + HMT; 100 g, 150 times/min). After 14 days of treatment, weight, improved
      Basso-Beattie-Bresnahan (BBB) locomotor score, and intestinal movement were
      evaluated. Morphological structure of spinal cord and colon tissues were
      examined. Immunostaining, RT-PCR, and western blot were used to assess c-kit
      expression. Results: In SCI rats, AMT could not restore BBB, but it significantly
      increased weight, shortened time to defecation, increased feces amounts, and
      improved fecal pellet traits and colon histology. AMT improved the number,
      distribution, and ultrastructure of colonic ICCs, increasing colonic c-kit mRNA
      and protein levels. Compared with the SCI + Drug and SCI + LMT groups, the SCI +
      HMT group showed better therapeutic effect in improving intestinal transmission
      function and promoting c-kit expression. Conclusions: AMT is an effective therapy
      for recovery of intestinal transmission function. It could repair ICCs and
      increase c-kit expression in colon tissues after SCI, in a frequency-dependent
      and pressure-dependent manner.

PMID- 29349062
TI  - Circular RNAs: Biogenesis, Function, and a Role as Possible Cancer Biomarkers.
AB  - Circular RNAs (circRNAs) are a class of noncoding RNAs (ncRNAs) that form
      covalently closed continuous loop structures, lacking the terminal 5' and 3'
      ends. CircRNAs are generated in the process of back-splicing and can originate
      from different genomic regions. Their unique circular structure makes circRNAs
      more stable than linear RNAs. In addition, they also display insensitivity to
      ribonuclease activity. Generally, circRNAs function as microRNA (miRNA) sponges
      and have a regulatory role in transcription and translation. They may be also
      translated in a cap-independent manner in vivo, to generate specific proteins. In
      the last decade, next-generation sequencing techniques, especially RNA-seq, have
      revealed great abundance and also dysregulation of many circRNAs in various
      diseases, suggesting their involvement in disease development and progression.
      Regarding their high stability and relatively specific differential expression
      patterns in tissues and extracellular environment (e.g., body fluids), they are
      regarded as promising novel biomarkers in cancer. Therefore, we focus this review
      on describing circRNA biogenesis, function, and involvement in human cancer
      development and address the potential of circRNAs to be effectively used as novel
      cancer diagnostic and prognostic biomarkers.

PMID- 29349064
TI  - From Clinical Symptoms to MR Imaging: Diagnostic Steps in Adenomyosis.
AB  - Adenomyosis or endometriosis genitalis interna is a frequent benign disease of
      women in fertile age. It causes symptoms like bleeding disorders and dysmenorrhea
      and seems to have a negative effect on fertility. Adenomyosis can be part of a
      complex genital and extragenital endometriosis but also can be found as a
      solitary uterine disease. While peritoneal endometriosis can be easily diagnosed
      by laparoscopy with subsequent biopsy, the determination of adenomyosis is
      difficult. In the following literature review, the diagnostic methods clinical
      history and symptoms, gynecological examination, 2D and 3D transvaginal
      ultrasound, MRI, hysteroscopy, and laparoscopy will be discussed step by step in
      order to evaluate their predictive value in the diagnosis of adenomyosis.

PMID- 29349065
TI  - Beneficial Effects of 6-Month Supplementation with Omega-3 Acids on Selected
      Inflammatory Markers in Patients with Chronic Kidney Disease Stages 1-3.
AB  - Introduction: Chronic kidney disease (CKD) is accompanied by inflammation. The
      aim of this study was to evaluate the effect of 6-month supplementation with
      omega-3 acids on selected markers of inflammation in patients with CKD stages 1
      3. Methods: Six-month supplementation with omega-3 acids (2 g/day) was
      administered to 87 CKD patients and to 27 healthy individuals. At baseline and
      after follow-up, blood was taken for C-reactive protein (CRP) and monocyte
      chemotactic protein-1 (MCP-1) concentration and white blood cell (WBC) count.
      Serum concentration of omega-3 acids-eicosapentaenoic acid (EPA), docosahexaenoic
      acid (DHA), and alpha-linolenic acid (ALA)-was determined using gas
      chromatography. And 24-hour urinary collection was performed to measure MCP-1
      excretion. Results: After six-month omega-3 supplementation, ALA concentration
      increased in CKD patients and in the reference group, while EPA and DHA did not
      change. At follow-up, a significant decrease in urinary MCP-1 excretion in CKD (p
      = 0.0012) and in the reference group (p = 0.001) was found. CRP, serum MCP-1, and
      WBC did not change significantly. The estimated glomerular filtration rate (eGFR)
      did not change significantly in the CKD group. Conclusions: The reduction of
      urinary MCP-1 excretion in the absence of MCP-1 serum concentration may suggest a
      beneficial effect of omega-3 supplementation on tubular MCP-1 production. Trial
      Registration: This study was registered in ClinicalTrials.gov (identifier:
      NCT02147002).

PMID- 29349066
TI  - Cadmium Exposure as a Putative Risk Factor for the Development of Pancreatic
      Cancer: Three Different Lines of Evidence.
AB  - Although profoundly studied, etiology of pancreatic cancer (PC) is still rather
      scant. Exposure to cadmium (Cd), a ubiquitous metal associated with well
      established toxic and carcinogenic properties, has been hypothesized to one
      putative cause of PC. Hence, we analyzed recently published observational
      studies, meta-analyses, and experimental animal and in vitro studies with the aim
      of summarizing the evidence of Cd involvement in PC development and describing
      the possible mechanisms. Consolidation of epidemiological data on PC and exposure
      to Cd indicated a significant association with an elevated risk of PC among
      general population exposed to Cd. Cadmium exposure of laboratory animals was
      showed to cause PC supporting the findings suggested by human studies. The
      concordance with human and animal studies is buttressed by in vitro studies,
      although in vitro data interpretation is problematic. In most instances, only
      significant effects are reported, and the concentrations of Cd are excessive,
      which would skew interpretation. Previous reports suggest that oxidative stress,
      apoptotic changes, and DNA cross-linking and hypermethylation are involved in Cd
      mediated carcinogenesis. Undoubtedly, a significant amount of work is still
      needed to achieve a better understanding of the Cd involvement in pancreatic
      cancer which could facilitate prevention, diagnosis, and therapy of this fatal
      disease.

PMID- 29349067
TI  - Modulation of Immune Function in Rats Using Oligosaccharides Extracted from Palm
      Kernel Cake.
AB  - To investigate the prebiotic and immunomodulatory effects of PKC extract
      (OligoPKC) a total of 24 male rats were randomly assigned to three treatment
      groups receiving basal diet (control), basal diet containing 0.5% OligoPKC, or
      basal diet containing 1% OligoPKC for four weeks. We found that OligoPKC had no
      significant effect on the tested growth parameters. However, it increased the
      size of the total and beneficial bacterial populations while reducing pathogen
      populations. OligoPKC increased the concentration of immunoglobulins in the serum
      and cecal contents of rats. It also enhanced the antioxidant capacity of the
      liver while reducing lipid peroxidation in liver tissue. OligoPKC affected the
      expression of genes involved in immune system function in the intestine.
      Therefore, OligoPKC could be considered a potential mannan-based prebiotic for
      humans and animals due to its beneficial effects on the health and well-being of
      the model rats.

PMID- 29349068
TI  - Restrictive Transfusion Strategy Does Not Affect Clinical Prognosis in Patients
      with Ectopic Pregnancy.
AB  - To assess the effects of restrictive transfusion strategy on hemoglobin (Hb)
      levels and prognosis in patients with ectopic pregnancy and severe hemorrhage
      undergoing emergency surgery, patient data were collected from 2012 to 2016.
      Following transfusion guidelines, restrictive transfusion was performed; at Hb
      levels of 60-70 to 100 g/L, transfusion was continued or not based on disease
      status. The patients were divided into four groups: blood loss < 400 ml (N1), 400
      799 ml (N2), 800-1199 ml (N3), and >=1200 ml (N4). Several prognosis parameters
      were assessed. Group N4 was further divided based on blood loss amounts (1200
      1999, 2000-2999, 3000-3999, and 4000-5000 ml) for subgroup analyses. Blood loss,
      hemoglobin levels at discharge, and American Society of Anesthesiologists (ASA)
      scores were not associated with patient prognostic parameters, including
      intensive care unit (ICU) occupancy, cure, and healing rates, and surgical
      complications and hospital stay. No statistically significant difference was
      obtained in hospital stay among N1, N2, and N3 groups. Compared with N1 patients,
      cases with blood loss >= 1200 ml had significantly longer hospital stay.
      Interestingly, hospital stay was correlated with surgical approach, location of
      pregnancy, and operation time. Restrictive transfusion strategy could be safely
      used for emergency surgery in ectopic pregnancy with acute blood loss.

PMID- 29349069
TI  - A Novel Methicillin-Resistant Staphylococcus aureus t11469 and a Poultry Endemic
      Strain t002 (ST5) Are Present in Chicken in Ebonyi State, Nigeria.
AB  - Background: The changing epidemiology of methicillin-resistant Staphylococcus
      aureus (MRSA) from a hospital-associated pathogen to an organism commonly found
      in the community and in livestock reflects an organism well-equipped to survive
      in diverse environments and adjust to different environmental conditions
      including antimicrobial use. Methods: We investigated the molecular epidemiology
      of S. aureus and MRSA in poultry in Ebonyi State, Nigeria. Samples were collected
      from 1800 birds on 9 different farms within the state. Positive isolates were
      tested for antibiotic susceptibility and molecular typing. Results: Prevalence in
      birds was 13.7% (247/1800). MRSA prevalence in poultry was 0.8%. The prevalence
      of MRSA in broilers and layers was 1.2% and 0.4%, respectively. All tested
      isolates were susceptible to vancomycin. Molecular analysis of the isolates
      revealed 3 spa types: t002, t084, and a novel spa type, t11469. The novel spa
      type t11469 belonged to sequence type ST5. Conclusion: The detection of t002 in
      chicken suggests the presence of livestock-associated MRSA in poultry in Ebonyi
      State. The detection of the new spa type t11469 in poultry that has not been
      characterised to ascertain its pathogenic potential remains a cause for concern,
      especially as some were found to carry PVL genes, a putative virulence factor in
      staphylococcal infection.

PMID- 29349070
TI  - EEG Recording and Online Signal Processing on Android: A Multiapp Framework for
      Brain-Computer Interfaces on Smartphone.
AB  - Objective: Our aim was the development and validation of a modular signal
      processing and classification application enabling online electroencephalography
      (EEG) signal processing on off-the-shelf mobile Android devices. The software
      application SCALA (Signal ProCessing and CLassification on Android) supports a
      standardized communication interface to exchange information with external
      software and hardware. Approach: In order to implement a closed-loop brain
      computer interface (BCI) on the smartphone, we used a multiapp framework, which
      integrates applications for stimulus presentation, data acquisition, data
      processing, classification, and delivery of feedback to the user. Main Results:
      We have implemented the open source signal processing application SCALA. We
      present timing test results supporting sufficient temporal precision of audio
      events. We also validate SCALA with a well-established auditory selective
      attention paradigm and report above chance level classification results for all
      participants. Regarding the 24-channel EEG signal quality, evaluation results
      confirm typical sound onset auditory evoked potentials as well as cognitive event
      related potentials that differentiate between correct and incorrect task
      performance feedback. Significance: We present a fully smartphone-operated,
      modular closed-loop BCI system that can be combined with different EEG amplifiers
      and can easily implement other paradigms.

PMID- 29349071
TI  - Effect of Ultrasound-Enhanced Transdermal Drug Delivery Efficiency of
      Nanoparticles and Brucine.
AB  - Brucine is the active component in traditional Chinese medicine "Ma-Qian-Zi"
      (Strychnos nux-vomica Linn), with capabilities of analgesic, anti-inflammatory,
      anti-tumor and so on. It is crucial how to break through the impact of cuticle
      skin which reduces the penetration of drugs to improve drug transmission rate.
      The aim of this study is to improve the local drug concentration by using
      ultrasound. We used fresh porcine skin to study the effects of ultrasound on the
      transdermal absorption of brucine under the influence of various acoustic
      parameters, including frequency, amplitude and irradiation time. The transdermal
      conditions of yellow-green fluorescent nanoparticles and brucine in skin samples
      were observed by laser confocal microscopy and ultraviolet spectrophotometry. The
      results show that under ultrasonic conditions, the permeability of the skin to
      the fluorescent label and brucine (e.g., the depth and concentration of
      penetration) is increased compared to its passive diffusion permeability. The
      best ultrasound penetration can make the penetration depth of more than 110
      microns, fluorescent nanoparticles and brucine concentration increased to 2-3
      times. This work will provide supportive data on how the brucine is better used
      for transdermal drug delivery (TDD).

PMID- 29349072
TI  - Complex Segregation Analysis Provides Evidence for Autosomal Dominant
      Transmission in the Chinese Han Families with Ankylosing Spondylitis.
AB  - Introduction: Familial aggregation of ankylosing spondylitis (AS) has been
      frequently noticed. However, the mode of inheritance in AS remains poorly
      understood. Our aim was to determine the mode of inheritance best fitting the
      observed transmission pattern of AS families. Methods: Families with 5 or more AS
      patients diagnosed with 1984 modified New York criteria were recruited. We
      performed complex segregation analysis for a binary trait in regressive
      multivariate logistic models. The inheritance models, including sporadic, major
      gene, environmental, general, and other 9 models, were compared by likelihood
      ratio tests and Akaike's Information Criterion. Results: This research included 9
      Chinese Han AS families with a total number of 315 persons, including 74
      patients. First, familial association was determined. Sporadic with familial
      association model was rejected when compared with either the general model or the
      homogeneous general model (p < 0.001). The environmental model was also rejected
      when compared with general models (p < 0.02). Mendelian dominate mode fitted best
      in 5 AS families, while Tau AB free model best explained the mode of inheritance
      in these AS families. Conclusion: This study provided evidence in support of
      Mendelian dominant mode and firstly discovered a non-Mendelian mode called tau AB
      free inheritance mode in AS.

PMID- 29349073
TI  - Anatomical Basis of the Myofascial Trigger Points of the Gluteus Maximus Muscle.
AB  - Myofascial pain syndrome is characterized by pain and limited range of motion in
      joints and caused by muscular contracture related to dysfunctional motor end
      plates and myofascial trigger points (MTrPs). We aimed to observe the anatomical
      correlation between the clinically described MTrPs and the entry point of the
      branches of the inferior gluteal nerve into the gluteus maximus muscle. We
      dissected twenty gluteus maximus muscles from 10 human adult cadavers (5 males
      and 5 females). We measured the muscles and compiled the distribution of the
      nerve branches into each of the quadrants of the muscle. Statistical analysis was
      performed by using Student's t-test and Kruskal-Wallis tests. Although no
      difference was observed either for muscle measurements or for distribution of
      nerve branching among the subjects, the topography of MTrPs matched the
      anatomical location of the entry points into the muscle. Thus, anatomical
      substract of the MTrPs may be useful for a better understanding of the
      physiopathology of these disorders and provide basis for their surgical and
      clinical treatment.

PMID- 29349074
TI  - Biomechanical Effects of Posterior Condylar Offset and Posterior Tibial Slope on
      Quadriceps Force and Joint Contact Forces in Posterior-Stabilized Total Knee
      Arthroplasty.
AB  - This study aimed to determine the biomechanical effect of the posterior condylar
      offset (PCO) and posterior tibial slope (PTS) in posterior-stabilized (PS) fixed
      bearing total knee arthroplasty (TKA). We developed +/-1, +/-2, and +/-3 mm PCO
      models in the posterior direction and -3 degrees , 0 degrees , 3 degrees , and 6
      degrees  PTS models using a previously validated FE model. The influence of
      changes in the PCO and PTS on the biomechanical effects under deep-knee-bend
      loading was investigated. The contact stress on the PE insert increased by 14%
      and decreased by 7% on average as the PCO increased and decreased, respectively,
      compared to the neutral position. In addition, the contact stress on post in PE
      insert increased by 18% on average as PTS increased from -3 degrees  to 6 degrees
      . However, the contact stress on the patellar button decreased by 11% on average
      as PTS increased from -3 degrees  to 6 degrees  in all different PCO cases. The
      quadriceps force decreased by 14% as PTS increased from -3 degrees  to 6 degrees 
      in all PCO models. The same trend was found in patellar tendon force. Changes in
      PCO had adverse biomechanical effects whereas PTS increase had positive
      biomechanical effects. However, excessive PTS should be avoided to prevent knee
      instability and subsequent failure.

PMID- 29349075
TI  - Influence of Restorative Materials on Color of Implant-Supported Single Crowns in
      Esthetic Zone: A Spectrophotometric Evaluation.
AB  - Restorations of 98 implant-supported single crowns in anterior maxillary area
      were divided into 5 groups: zirconia abutment, titanium abutment, and gold/gold
      hue abutment with zirconia coping, respectively, and titanium abutment with metal
      coping as well as gold/gold hue abutment with metal coping. A reflectance
      spectrophotometer was used to evaluate the color difference between the implant
      crowns and contralateral/neighboring teeth, as well as the color difference
      between the peri-implant soft tissue and the natural marginal mucosa. The mucosal
      discoloration score was used for subjective evaluation of the esthetic outcome of
      soft tissue around implant-supported single crowns in the anterior zone, and the
      crown color match score was used for subjective evaluation of the esthetic
      outcome of implant-supported restoration. ANOVA analysis was used to compare the
      differences among groups and Spearman correlation was used to test the
      relationships. A gold/gold hue abutment with zirconia coping was the best choice
      for an esthetic crown and the all-ceramic combination was the best for peri
      implant soft tissue. Significant correlation was found between the
      spectrophotometric color difference of peri-implant soft tissue and mucosal
      discoloration score, while no significant correlation was found between the total
      spectrophotometric color difference of implant crown and crown color match score.

PMID- 29349076
TI  - The Association between 5HT2A T102C and Behavioral and Psychological Symptoms of
      Dementia in Alzheimer's Disease: A Meta-Analysis.
AB  - The serotonin receptor gene (5-HT2A) has been reported to be a susceptible factor
      in behavioral and psychological symptoms of dementia (BPSD) in Alzheimer's
      disease (AD). However, previous results were conflicting. We aim to investigate
      the association of 5-HT2A T102C with BPSD in AD using a meta-analysis. 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. Nine
      studies with 1899 AD patients with/without BPSD were included in this meta
      analysis. The 102C and CC genotypes were associated with psychosis in AD (102C: p
      < 0.00001, OR [95% CI] = 3.19 [2.12-4.79]; CC: p < 0.00001, OR [95% CI] = 7.24
      [3.60-14.59]). The TT genotype was significantly associated with hallucinations,
      aberrant motor behavior, and psychosis in AD (hallucinations: p = 0.001, OR [95%
      CI] = 0.52 [0.36-0.77]; aberrant motor behavior: p = 0.03, OR [95% CI] = 0.58
      [0.35-0.95]; and psychosis: p = 0.002, OR [95% CI] = 0.34 [0.17-0.67]). No
      association was observed between T102C alleles or genotypes and delusions,
      agitation/aggression, depression, and apathy (p > 0.05). Thus, the 5HT2A T102C
      might be a susceptible factor for hallucinations, aberrant motor behavior, and
      psychosis in AD. The potential mechanism of this polymorphism in BPSD in AD
      requires further exploration.

PMID- 29349077
TI  - The Prognostic Value of HRAS mRNA Expression in Cutaneous Melanoma.
AB  - This study aimed to investigate the prognostic value of HRAS mRNA expression in
      cutaneous melanoma. Cutaneous melanoma is an aggressive cancer with an increasing
      incidence. Few studies have focused on the transcriptional level of RAS isoforms
      (KRAS, NRAS, and HRAS) in cutaneous melanoma. To gain further insight into RAS
      isoforms at transcriptional level, we obtained the cutaneous melanoma data from
      cBioPortal and investigated the RAS mRNA expression levels in different stages of
      melanoma and evaluated their correlation with clinical characteristics and
      patients' survival. Furthermore, we retrieved and analyzed the coexpression data
      and performed pathway enrichment analysis. Totally, 452 cutaneous melanoma cases
      were included in this study. We found that lower HRAS expression level was
      associated with longer patient survival. 206 genes that negatively correlated
      with HRAS expression were positively correlated with KRAS and NRAS expression. In
      contrast, no gene that positively correlated with HRAS expression was positively
      correlated with KRAS and NRAS expression. In conclusion, our data showed that
      transcriptional regulation was different for the three RAS isoforms in cutaneous
      melanoma. This study highlighted the prognostic value of HRAS mRNA expression and
      revealed that HRAS greatly differs from KRAS and NRAS at the transcriptional
      level.

PMID- 29349078
TI  - Categorisation of Mobile EEG: A Researcher's Perspective.
AB  - Researchers are increasingly attempting to undertake electroencephalography (EEG)
      recordings in novel environments and contexts outside of the traditional static
      laboratory setting. The term "mobile EEG," although commonly used to describe
      many of these undertakings, is ambiguous, since it attempts to encompass a wide
      range of EEG device mobility, participant mobility, and system specifications
      used across investigations. To provide quantitative parameters for "mobile EEG,"
      we developed a Categorisation of Mobile EEG (CoME) scheme based upon scoring of
      device mobility (D, from 0, off-body, to 5, head-mounted with no additional
      equipment), participant mobility (P, from 0, static, to 5, unconstrained
      running), system specification (S, from 4, lowest, to 20, highest), and number of
      channels (C) used. The CoME scheme was applied to twenty-nine published mobile
      EEG studies. Device mobility scores ranged from 0D to 4D, participant mobility
      scores from 0P to 4P, and system specification scores from 6S to 17S. The format
      of the scores for the four parameters is given, for example, as (2D, 4P, 17S,
      32C) and readily enables comparisons across studies. Our CoME scheme enables
      researchers to quantify the degree of device mobility, participant mobility, and
      system specification used in their "mobile EEG" investigations in a standardised
      way.

PMID- 29349079
TI  - Advances of Techniques in Deep Regional Blocks.

PMID- 29349080
TI  - Comparative Analysis and Classification of Cassette Exons and Constitutive Exons.
AB  - Alternative splicing (AS) is a major engine that drives proteome diversity in
      mammalian genomes and is a widespread cause of human hereditary diseases. More
      than 95% of genes in the human genome are alternatively spliced, and the most
      common type of AS is the cassette exon. Recent discoveries have demonstrated that
      the cassette exon plays an important role in genetic diseases. To discover the
      formation mechanism of cassette exon events, we statistically analyze cassette
      exons and find that cassette exon events are strongly influenced by individual
      exons that are smaller in size and that have a lower GC content, more codon
      terminations, and weaker splice sites. We propose an improved random-forest-based
      hybrid method of distinguishing cassette exons from constitutive exons. Our
      method achieves a high accuracy in classifying cassette exons and constitutive
      exons and is verified to outperform previous approaches. It is anticipated that
      this study will facilitate a better understanding of the underlying mechanisms in
      cassette exons.

PMID- 29349081
TI  - Quality of Life in Workers and Stress: Gender Differences in Exposure to
      Psychosocial Risks and Perceived Well-Being.
AB  - Background: Quality of working life is the result of many factors inherent in the
      workplace environment, especially in terms of exposure to psychosocial risks.
      Objectives: The purpose of this study is to assess the quality of life with
      special attention to gender differences. Methods: The HSE-IT questionnaire and
      the WHO-5 Well-Being Index were administered to a group of workers (74 males and
      33 females). The authors also used Cronbach's alpha test to assess the internal
      consistency of both questionnaires and the Mann-Whitney test to evaluate the
      significance of gender differences in both questionnaires. Results: The HSE-IT
      highlighted the existence of work-related stress in all the population with a
      critical perception regarding the domain "Relationships." Furthermore, gender
      analysis highlighted the presence of two additional domains in the female
      population: "Demand" (p = 0,002) and "Support from Managers" (p = 0,287). The WHO
      5 highlighted a well-being level below the standard cut-off point with a
      significant gender difference (p = 0.009) for males (18, SD = 6) as compared to
      females (14, SD = 6,4). Cronbach's alpha values indicated a high level of
      internal consistency for both of our scales. Conclusions: The risk assessment of
      quality of working life should take into due account the individual
      characteristics of workers, with special attention to gender.

PMID- 29349082
TI  - Efficacy of One-Year Treatment with Aflibercept for Diabetic Macular Edema with
      Practical Protocol.
AB  - The purpose of this study was to determine the efficacy of one-year treatment of
      diabetic macular edema (DME) with intravitreal aflibercept (IVA) injections on a
      practical protocol. The medical records of 51 eyes of 43 patients who were
      diagnosed with DME and had received IVA treatments were reviewed. The best
      corrected visual acuity (BCVA) and the central macular thickness (CMT) were
      measured at the baseline and at 1, 3, 6, and 12 months after the IVA. The mean
      number of IVA injections was 3.8 +/- 2.4. The mean BCVA was significantly better
      and the CMT was thinner after the IVA at all follow-up times (P < 0.05). The BCVA
      was better in eyes with a serous retinal detachment (SRD) than without a SRD (P <
      0.01). There was a significant correlation between the photoreceptor outer
      segment (PROS) length and BCVA at the baseline and at 12 months after the IVA (P
      < 0.05). A fewer number of IVA injections significantly improved the BCVA and the
      CMT in eyes with DME after one-year treatment. IVA was more effective in the SRD+
      group than in the SRD- group. The PROS length may be a predictive marker for
      visual outcomes after one-year treatment with IVA for DME (IRB#2272).

PMID- 29349083
TI  - Effects of Two Current Great Saphenous Vein Thermal Ablation Methods on Visual
      Analog Scale and Quality of Life.
AB  - Background: The aim of the study is to compare the current two endovenous thermal
      ablation methods by examining the effects on the visual analog scale (VAS) and
      the short form-36(r) quality of life index. Methods: Ninety-six patients who
      underwent unilateral endovenous thermal ablation of great saphenous vein were
      included. ClosureFastTM catheters were used in the RFA group and 1470 nm radial
      fiber laser catheters were used in the EVLA group. Results: The RFA group
      consisted of 41 patients and the EVLA group consisted of 55 patients. The
      preoperative baseline characteristics of both groups were similar. On the day of
      operation, VAS values were 2.8 +/- 1.1 in the RFA group and 3.6 +/- 1.8 in the
      EVLA group (p = 0.02). Comparisons of short form-36 parameters in both groups
      showed them to be similar except the pain detected at postoperative 1st week
      (48.1 +/- 5.4 for RFA, 44.9 +/- 7.6 for EVLA, p = 0.04). Conclusion: Results in
      postprocedural quality of life were found to be similar in both of the
      techniques. However, in terms of postoperative pain, radiofrequency ablation is
      still superior to the 1470 nm radial fiber laser catheters.

PMID- 29349084
TI  - In Vitro Biological Screening of Hartmannia rosea Extracts.
AB  - The present study is focused on the assessment of the medicinal therapeutic
      potential extracts of H. rosea to investigate their pharmacological implications
      based upon science proofs. The antioxidant activity of fraction of H. rosea,
      namely, n-hexane (HR-1), ethyl acetate (HR-2), chloroform (HR-3), and n-butanol
      (HR-4), was performed by using the DPPH radical scavenging method. The
      cytotoxicity and enzyme inhibition assessment were also performed. All the
      extracts showed significant antioxidant, antibacterial, and protein kinase
      inhibition but none of the extracts exhibited alpha-amylase inhibition activity.
      The chloroform extract HR-3 may block a kinase receptor from binding to ATP; the
      lead molecule will be isolated, which may stop cancerous cell growth and demotion
      of cell division. It is predicted that ethyl acetate, chloroform, and n-butanol
      extracts of H. rosea contain polyphenolics, flavonoids, and alkaloids that are
      biologically effective candidates exhibiting significant cytotoxicity,
      antioxidant, and antimicrobial activities. They may control oxidative damage in
      the body tissues and act as potential antidiabetic and anticancer agents. These
      studies will also be helpful for future drug designing and drug development
      research.

PMID- 29349085
TI  - Preimplantation Genetic Diagnosis for Myotonic Dystrophy Type 1 and Analysis of
      the Effect of the Disease on the Reproductive Outcome of the Affected Female
      Patients.
AB  - Myotonic dystrophy type 1 (DM1) is the most common adult muscular dystrophy and
      presents an autosomal dominant inheritance. A reproductive option for the
      families affected is preimplantation genetic diagnosis (PGD). One limitation of
      this option is the nonoptimal response to ovarian stimulation of the women with
      DM1, although controversial results exist regarding this subject. In this study,
      we have analyzed the results of the PGD program applied to DM1 at our
      institution. A total of 35 couples have been included in our program since 2010,
      and 59 cycles have been performed. The percentage of transfers per cycle was
      64.4% and the live birth rate per cycle was 18.6%. Interestingly, statistically
      significant differences were observed for the clinical results in the group of
      couples with an affected female versus the group with an affected male or versus
      a group of couples with different referral reasons. Specifically, both the
      percentage of mature oocytes out of the total oocytes retrieved and the
      percentage of fertilization were considerably lower in the group of DM1 females.
      Our findings would suggest the possibility of achieving less favourable PGD
      outcomes in women with DM1 in comparison with other pathologies, although the
      underlying mechanism remains unknown.

PMID- 29349086
TI  - Preparation of P3HB4HB/(Gelatin + PVA) Composite Scaffolds by Coaxial
      Electrospinning and Its Biocompatibility Evaluation.
AB  - This study was conducted to prepare coaxial electrospun scaffolds of
      P3HB4HB/(gelatin + PVA) with various concentration ratios with P3HB4HB as the
      core solution and gelatin + PVA mixture as the shell solution; the mass ratios of
      gelatin and PVA in each 10 mL shell mixture were 0.6 g : 0.2 g (Group A), 0.4 g :
      0.4 g (Group B), and 0.2 g : 0.6 g (Group C). The results showed that the pore
      size, porosity, and cell proliferation rate of Group C were better than those of
      Groups A and B. The ascending order of the tensile strength and modulus of
      elasticity was Group A < Group B < Group C. The surface roughness was Group C >
      Group B > Group A. The osteogenic and chondrogenic-specific staining showed that
      Group C was stronger than Groups A and B. This study demonstrates that when the
      mass ratio of gelatin : PVA was 0.2 g : 0.6 g, a P3HB4HB/(gelatin + PVA)
      composite scaffold with a core-shell structure can be prepared, and the scaffold
      has good biocompatibility that it may be an ideal scaffold for tissue
      engineering.

PMID- 29349088
TI  - Corrigendum to "Antidiabetic Effect of Young and Old Ethanolic Leaf Extracts of
      Vernonia amygdalina: A Comparative Study".
AB  - [This corrects the article DOI: 10.1155/2016/8252741.].

PMID- 29349087
TI  - Advances and Current Concepts in the Medical Management of Gastroenteropancreatic
      Neuroendocrine Neoplasms.
AB  - Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are rare and
      heterogeneous group of tumors presenting as localised or metastatic disease and
      in a subset with distinct clinical syndromes. Treatment is aimed at controlling
      the functional syndrome, eradicating the tumor, and/or preventing further tumor
      growth. Surgery is the treatment of choice in removing the primary tumor and/or
      reducing tumor burden but cannot be applied to all patients. Somatostatin analogs
      (SS-analogs) obtain control of functional syndromes in the majority of GEP
      neuroendocrine tumors (NETs); phase III trials have shown that SS-analogs can be
      used as first-line antiproliferative treatment in patients with slow-growing GEP
      NETs. The role of the recently approved serotonin inhibitor, telotristat ethyl,
      and gastrin receptor antagonist, netazepide, is evolving. Streptozotocin-based
      chemotherapy has been used for inoperable or progressing pancreatic NENs but the
      orally administered combination of capecitabine/temozolomide is becoming more
      popular due to its better tolerability and potential effect in other GEP-NENs.
      Phase III trials have shown efficacy of molecular targeted therapies in GEP-NETs
      and of radionuclide treatment in patients with midgut carcinoid tumors expressing
      somatostatin receptors. Most patients will develop disease progression
      necessitating further therapeutic options. A combination of currently available
      treatments along with the molecular signature of each tumor will guide future
      treatment.

PMID- 29349089
TI  - Elevated Levels of Interferon-gamma Are Associated with High Levels of Epstein
      Barr Virus Reactivation in Patients with the Intestinal Type of Gastric Cancer.
AB  - Background: The inflammatory response directed against Helicobacter pylori (HP)
      is believed to be one of the main triggers of the appearance of gastric lesions
      and their progression to gastric cancer (GC). Epstein-Barr virus (EBV) has been
      found responsible for about 10% of all GCs, but the inflammatory response has not
      been studied in GC patients with evidence of high levels of EBV reactivation.
      Objective: To determine the relationship between inflammation and antibodies
      against EBV reactivation antigens, HP, and the bacterium virulence factor CagA in
      patients with GC. Methods: 127 GC patients, 46 gastritis patients, and 197
      healthy subjects were studied. IL-1beta, IL-6, IL-8, IL-10, TNF-alpha, TGF-beta,
      MCP-1, and IFN-gamma levels were measured in serum or plasma and compared against
      the antibody titers of VCA-IgG, HP, and the HP virulence factor CagA. Statistical
      associations were estimated. Results: Significant ORs and positive trends were
      found between VCA-IgG and IFN-gamma, specifically for patients with GC of
      intestinal type (OR: 6.4, 95% C.I. 1.2-35.4) (p < 0.044). Conclusions: We
      confirmed a positive association between a marker of EBV reactivation and
      intestinal gastric cancer and present evidence of a correlation with elevated
      serum levels of IFN-gamma, but not with the other cytokines.

PMID- 29349091
TI  - Coexistent Ipsilateral Internal Carotid Artery Occlusion and Cerebral Venous
      Thrombosis in Hepatitis C.
AB  - A 58-year-old male, known to have hepatitis C virus (HCV), presented with
      intermittent headaches and left-sided sensorimotor symptoms. There were no focal
      neurological deficits on examination. Electrocardiogram was unremarkable.
      Computed tomography angiography head and neck displayed extracranial right
      internal carotid artery occlusion. Magnetic resonance imaging showed right
      cortical vein thrombosis, with hemorrhagic infarction. Echocardiography with
      bubble study was unremarkable. Hypercoagulable workup was significant for protein
      S deficiency. He was treated with warfarin for 6 months. Repeat protein S levels
      remained low 9 months later. The coexistence of arterial and venous thrombotic
      events gives rise to a limited differential. In this case, it may be related to
      chronic HCV infection. The underlying pathogenesis is not clear; however, it is
      possible the patient had chronic high-grade internal carotid artery stenosis,
      which occluded leading to his presenting symptoms. The cortical vein thrombosis
      is likely an incidental finding here. The extent by which HCV contributed to the
      cerebral thrombosis and carotid artery occlusion in our case is not clear;
      however, the hypercoagulable and atherosclerotic properties of the virus cannot
      be disregarded. The virus can promote carotid atherosclerosis and cerebral venous
      thrombosis as well as other venous and arterial thromboembolic events.
      Furthermore, HCV is associated with impaired venous flow and procoagulant
      properties, which can fuel a hypercoagulable state. Also of note cirrhosis is
      associated with protein S deficiency. We recommend considering an underlying
      hypercoagulable state including both arterial and venous thrombosis in HCV
      infection.

PMID- 29349090
TI  - Dysregulation of miR-155-5p and miR-200-3p and the Anti-Non-Bilayer Phospholipid
      Arrangement Antibodies Favor the Development of Lupus in Three Novel Murine Lupus
      Models.
AB  - Systemic lupus erythematosus (SLE) is characterized by deregulated activation of
      T and B cells, autoantibody production, and consequent formation of immune
      complexes. Liposomes with nonbilayer phospholipid arrangements (NPA), induced by
      chlorpromazine, procainamide, or manganese, provoke a disease resembling human
      lupus when administered to mice. These mice produce anti-NPA IgM and IgG
      antibodies and exhibit an increased number of TLR-expressing spleen cells and a
      modified gene expression associated with TICAM1-dependent TLR-4 signaling
      (including IFNA1 and IFNA2) and complement activation. Additionally, they showed
      a diminished gene expression related to apoptosis and NK cell activation. We
      hypothesized that such gene expression may be affected by miRNAs and so miRNA
      expression was studied. Twelve deregulated miRNAs were found. Six of them were
      common to the three lupus-like models. Their validation by qRT-PCR and TaqMan
      probes, including miR-342-3p, revealed that miR-155-5p and miR-200a-3p expression
      was statistically significant. Currently described functions for these miRNAs in
      autoimmune diseases such as SLE reveal their participation in inflammation,
      interferon production, germinal center responses, and antibody maturation. Taking
      into account these findings, we propose miR-155-5p and miR-200a-3p, together with
      the anti-NPA antibodies, as key players in the murine lupus-like models and
      possible biomarkers of the human SLE.

PMID- 29349092
TI  - Cathepsin B plays a key role in optimal production of the influenza A virus.
AB  - Background: Influenza A virus (IAV) is the etiologic agent of the febrile
      respiratory illness, commonly referred to as 'flu'. The lysosomal protease
      cathepsin B (CTSB) has shown to be involved in the lifecycle of various viruses.
      Here, we examined the role of CTSB in the IAV lifecycle. Methods: CTSB-deficient
      (CTSB-/-) macrophages and the human lung epithelial cell line A549 cells treated
      with CA-074Me were infected with the A/Puerto Rico/8/34 strain of IAV (IAV-PR8).
      Viral entry and propagation were measured through quantitative real-time RT-PCR;
      production and localization of hemagglutinin (HA) protein in the infected host
      cells were analysed by Western blots, flow cytometry and confocal microscopy;
      production of progeny viruses were measured by a hemagglutination assay. Results:
      CTSB-/- macrophages and CA-074Me-treated A549 cells had no defects in
      incorporating IAV-PR8 virions and permitting viral RNA synthesis. However, these
      cells produced significantly lower amounts of HA protein and progeny virions than
      wild-type or untreated cells. Conclusion: These data indicate that CTSB is
      involved in the expression of IAV-PR8 HA protein and subsequent optimal
      production of IAV-PR8 progeny virions. Targeting CTSB can be a novel therapeutic
      strategy for treating IAV infection.

PMID- 29349093
TI  - Preseason Adductor Squeeze Strength in 303 Spanish Male Soccer Athletes: A Cross
      sectional Study.
AB  - Background: Hip adductor muscle weakness and a history of groin injury both have
      been identified as strong risk factors for sustaining a new groin injury. Current
      groin pain and age have been associated with hip adductor strength. These factors
      could be related, but this has never been investigated. Purpose: To investigate
      whether soccer athletes with past-season groin pain and with different durations
      of past-season groin pain had lower preseason hip adductor squeeze strength
      compared with those without past-season groin pain. We also investigated whether
      differences in preseason hip adductor squeeze strength in relation to past-season
      groin pain and duration were influenced by current groin pain and age. Study
      Design: Cross-sectional study; Level of evidence, 3. Methods: In total, 303 male
      soccer athletes (mean age, 23 +/- 4 years; mean weight, 74.0 +/- 7.9 kg; mean
      height, 178.1 +/- 6.3 cm) were included in this study. Self-reported data
      regarding current groin pain, past-season groin pain, and duration were
      collected. Hip adductor squeeze strength was obtained using 2 different reliable
      testing procedures: (1) the short-lever (resistance placed between the knees,
      feet at the examination bed, and 45 degrees  of hip flexion) and (2) the long
      lever (resistance placed between the ankles and 0 degrees  of hip flexion)
      squeeze tests. Results: There was no difference between those with (n = 123) and
      without (n = 180) past-season groin pain for hip adductor squeeze strength when
      adjusting for current groin pain and age. However, athletes with past-season
      groin pain lasting longer than 6 weeks (n = 27) showed 11.5% and 15.3% lower
      values on the short-lever (P = .006) and long-lever (P < .001) hip adductor
      squeeze strength tests, respectively, compared with those without past-season
      groin pain. Conclusion: Male soccer athletes with past-season groin pain lasting
      longer than 6 weeks are likely to begin the next season with a high-risk groin
      injury profile, including a history of groin pain and hip adduction weakness.

PMID- 29349094
TI  - Upper Extremity Functional Status of Female Youth Softball Pitchers Using the
      Kerlan-Jobe Orthopaedic Clinic Questionnaire.
AB  - Background: Softball is a popular sport with a high incidence of upper extremity
      injuries. The Kerlan-Jobe Orthopaedic Clinic (KJOC) questionnaire is a validated
      performance and functional assessment tool used in overhead athletes. Upper
      extremity pain patterns and baseline KJOC scores have not been reported for
      active female youth softball pitchers. Purpose/Hypothesis: The purpose of this
      study was to establish the prevalence of upper extremity pain and its effect in
      female youth softball pitchers over a competitive season. We hypothesized that
      participants who missed time due to injury in the past year would have lower KJOC
      scores. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Fifty
      three female softball pitchers aged 12 to 18 years were recruited from softball
      clinics in Vancouver, British Columbia, Canada. All participants self-identified
      as a pitcher on a competitive travel team. Participants were administered the
      KJOC questionnaire before and during the playing season. Missed time due to
      injury in the past year, current pain patterns, and KJOC scores were primary
      outcomes. Results: The mean (+/-SD) preseason KJOC score was 87.2 +/- 10.6. In
      the preseason, 22.6% of pitchers reported playing with arm trouble, and 32.1%
      missed time due to injury in the past year. The mean KJOC score for pitchers
      reporting a previous injury (n = 17) was significantly lower compared with those
      without an injury (n = 36) (79.5 +/- 13.8 vs 90.9 +/- 6.2, respectively; P =
      .02). The posterior shoulder was the most commonly reported pain location. For
      the cohort completing the questionnaire both before and during the playing season
      (n = 35), mean KJOC scores did not change significantly over the playing season
      (P = .64). Lower preseason KJOC scores were significantly related to the in
      season injury risk (P = .016). Pitchers with a preseason score of less than 90
      had a 3.5 (95% CI, 1.1-11.2) times greater risk of reporting an in-season injury.
      Conclusion: Female youth softball pitchers have a high baseline functional
      status. However, 1 in 3 pitchers reported missed time due to injury in the
      previous year, and shoulder pain was more prevalent than elbow pain. The KJOC
      questionnaire can be used by coaches, researchers, and clinicians to identify
      youth softball pitchers at risk for injuries who may benefit from interventions.

PMID- 29349095
TI  - Spinal Motocross Injuries in the United Kingdom.
AB  - Background: Motocross is a form of motorcycle racing held on established off-road
      circuits and has been a recreational and competitive sport across the world for
      >100 years. In the United Kingdom alone, motocross has grown into a phenomenally
      ambitious and popular franchise. There are >200 motocross clubs across the
      country, permitting >900 events annually. Purpose: To assess the current trend of
      spine-related motocross injuries over the past 5 years. Study Design: Descriptive
      epidemiology study. Methods: Data were prospectively collected over 5 years
      (August 2010-August 2015) at our regional trauma and spine unit, regardless of
      whether the rider was performing the sport competitively or recreationally.
      Results: During the study period, spine-related injuries were identified for 174
      patients (age range, 6-75 years) who were directly referred to our department
      following recreational or competitive motocross, with most injuries being
      sustained within the early spring and summer months, representing the start of
      the motocross season. A significant number of injuries were in males (n = 203,
      94%), with the majority of injuries occurring within the 21- to 30-year-old age
      group. A total of 116 (54%) injuries required operative treatment. The most
      common spinal injury was thoracolumbar burst fracture (n = 95), followed by
      chance fractures (n = 26). Conclusion: This data series emphasizes the prevalence
      and devastation of motocross-related spinal injuries in the United Kingdom and
      may serve in administering sanctions and guidelines to governing bodies of
      motocross. The spinal injuries that occur during motocross have significant
      capital connotations for regional spinal centers. The recent surge in motocross
      popularity is correlated with the number of injuries, which have increased over
      the past 5 years by almost 500%.

PMID- 29349097
TI  - Universal Method for the Purification of Recombinant AAV Vectors of Differing
      Serotypes.
AB  - The generation of clinical good manufacturing practices (GMP)-grade adeno
      associated virus (AAV) vectors requires purification strategies that support the
      generation of vectors of high purity, and that exhibit a good safety and efficacy
      profile. To date, most reported purification schemas are serotype dependent,
      requiring method development for each AAV gene therapy product. Here, we describe
      a platform purification process that is compatible with the purification of
      multiple AAV serotypes. The method generates vector preparations of high purity
      that are enriched for capsids with full vector genomes, and that minimizes the
      fractional content of empty capsids. The two-column purification method, a
      combination of affinity and ion exchange chromatographies, is compatible with a
      range of AAV serotypes generated by either the transient triple transfection
      method or the more scalable producer cell line platform. In summary, the
      adaptable purification method described can be used for the production of a
      variety of high-quality AAV vectors suitable for preclinical testing in animal
      models of diseases.

PMID- 29349098
TI  - Comparison of HIV Testing among Children and Adults with Tuberculosis, Vietnam.
AB  - HIV testing among persons with tuberculosis (TB) results in high-yield
      identification of persons infected with HIV. To evaluate differences in HIV
      testing among children versus adults with TB in Vietnam, we collected and
      analyzed age-disaggregated facility and aggregated provincial data from the
      National Tuberculosis Program. HIV testing was incompletely documented for >70%
      of children, whereas adult testing data were >90% complete. Standardized training
      of personnel for universal HIV testing and documentation for children with TB
      could improve HIV case-detection and permit linking of children with HIV to
      antiretroviral treatment to prevent morbidity and mortality.

PMID- 29349096
TI  - Safety and Efficacy of AAV Retrograde Pancreatic Ductal Gene Delivery in Normal
      and Pancreatic Cancer Mice.
AB  - Recombinant adeno-associated virus (rAAV)-mediated gene delivery shows promise to
      transduce the pancreas, but safety/efficacy in a neoplastic context is not well
      established. To identify an ideal AAV serotype, route, and vector dose and assess
      safety, we have investigated the use of three AAV serotypes (6, 8, and 9)
      expressing GFP in a self-complementary (sc) AAV vector under an EF1alpha promoter
      (scAAV.GFP) following systemic or retrograde pancreatic intraductal delivery.
      Systemic delivery of scAAV9.GFP transduced the pancreas with high efficiency, but
      gene expression did not exceed >45% with the highest dose, 5 * 1012 viral genomes
      (vg). Intraductal delivery of 1 * 1011 vg scAAV6.GFP transduced acini, ductal
      cells, and islet cells with >50%, ~48%, and >80% efficiency, respectively, and
      >80% pancreatic transduction was achieved with 5 * 1011 vg. In a KrasG12D-driven
      pancreatic cancer mouse model, intraductal delivery of scAAV6.GFP targeted acini,
      epithelial, and stromal cells and exhibited persistent gene expression 5 months
      post-delivery. In normal mice, intraductal delivery induced a transient increase
      in serum amylase/lipase that resolved within a day of infusion with no sustained
      pancreatic inflammation or fibrosis. Similarly, in PDAC mice, intraductal
      delivery did not increase pancreatic intraepithelial neoplasia
      progression/fibrosis. Our study demonstrates that scAAV6 targets the
      pancreas/neoplasm efficiently and safely via retrograde pancreatic intraductal
      delivery.

PMID- 29349099
TI  - Repetitive Questioning Exasperates Caregivers.
AB  - Repetitive questioning is due to an impaired episodic memory and is a frequent,
      often presenting, problem in patients with Alzheimer's disease (amnestic type).
      It is due to the patients' difficulties learning new information, retaining it,
      and recalling it, and is often aggravated by a poor attention span and easy
      distractibility. A number of factors may trigger and maintain repetitive
      questioning. Caregivers should try to identify and address these triggers. In the
      case discussion presented, it is due to the patient's concerns about her and her
      family's safety triggered by watching a particularly violent movie aired on TV.
      What went wrong in the patient/caregiver interaction and how it could have been
      avoided or averted are explored. Also reviewed are the impact of repetitive
      questioning, the challenges it raises for caregivers, and some effective
      intervention strategies that may be useful to diffuse the angst that caregivers
      experience with repetitive questioning.

PMID- 29349100
TI  - Vitamin D Deficiency Associated With Markers of Cardiovascular Disease in
      Children With Obesity.
AB  - Adult studies have reported associations of low 25-hydroxyvitamin D (25OHD) with
      dyslipidemia and cardiovascular disease; however, there are scarce pediatric data
      regarding relationships between vitamin D status and specific lipid markers
      affecting cardiovascular risk. In this cross-sectional study of children
      evaluated at university-based pediatric endocrinology clinics, 178 patients
      meeting criteria for overweight or obesity had 25OHD levels assessed over a 2
      year period; 60 of 178 had non-HDL (high-density lipoprotein) cholesterol and
      fasting lipid parameters performed. Patients with 25OHD <20 ng/mL had
      significantly higher non-HDL cholesterol (134.76 +/- 47.32 vs 108.85 +/- 31.14, P
      < .03), triglyceride (TG)/HDL ratio (3.09 +/- 2.26 vs 1.82 +/- 1.18, P = .03),
      total cholesterol (TC)/HDL ratio (4.23 +/- 1.23 vs 3.40 +/- 1.05, P < .01), TC
      (184.15 +/- 40.19 vs 158.89 +/- 30.10, P < .01), and TG (134.76 +/- 47.32 vs
      78.93 +/- 37.46, P < .03) compared with 25OHD >=20 ng/mL. Vitamin D deficiency
      was significantly associated with increase in atherogenic lipids and markers of
      early cardiovascular disease. These findings suggest that vitamin D deficiency
      may have negative effects on lipid parameters with increase in cardiovascular
      risk.

PMID- 29349101
TI  - Multilayered complex network datasets for three supply chain network archetypes
      on an urban road grid.
AB  - This article presents the multilayered complex network formulation for three
      different supply chain network archetypes on an urban road grid and describes how
      500 instances were randomly generated for each archetype. Both the supply chain
      network layer and the urban road network layer are directed unweighted networks.
      The shortest path set is calculated for each of the 1 500 experimental instances.
      The datasets are used to empirically explore the impact that the supply chain's
      dependence on the transport network has on its vulnerability in Viljoen and
      Joubert (2017) [1]. The datasets are publicly available on Mendeley (Joubert and
      Viljoen, 2017) [2].

PMID- 29349102
TI  - Data on the clinical usefulness of brachial-ankle pulse wave velocity in patients
      with suspected coronary artery disease.
AB  - Brachial-artery pulse wave velocity (baPWV) is a simple and reliable tool for
      measurement of arterial stiffness. Our previous studies suggested that baPWV is
      associated with the presence and severity of coronary artery disease (CAD) and
      the risk of cardiovascular events. In the present data article, we provided
      supplementary data supporting the independent prognostic value of arterial
      stiffness, assessed by baPWV, in patients with suspected CAD (Hwang et al., 2017)
      [1]. The data was obtained from 523 patients undergoing coronary CT angiography
      (CCTA), and baPWV was measured at the time of CCTA. Patients with vulnerable
      coronary plaque or obstructive CAD on CCTA had higher age, more cardiovascular
      risk factors, and higher baPWV values. Given the significant association between
      high baPWV and the presence of vulnerable plaque or obstructive CAD as shown in
      this data article, the prognostic value of baPWV was further assessed in
      subgroups divided according to the CCTA findings (vulnerable plaque or
      obstructive CAD). In each subgroup by CCTA findings, multivariable Cox
      proportional hazard model analysis showed that high baPWV was an independent risk
      factor for cardiovascular events even after adjusting for clinical risk factors.

PMID- 29349103
TI  - Wildfire spread, hazard and exposure metric raster grids for central Catalonia.
AB  - We provide 40 m resolution wildfire spread, hazard and exposure metric raster
      grids for the 0.13 million ha fire-prone Bages County in central Catalonia
      (northeastern Spain) corresponding to node influence grid (NIG), crown fraction
      burned (CFB) and fire transmission to residential houses (TR). Fire spread and
      behavior data (NIG, CFB and fire perimeters) were generated with fire simulation
      modeling considering wildfire season extreme fire weather conditions (97th
      percentile). Moreover, CFB was also generated for prescribed fire (Rx) mild
      weather conditions. The TR smoothed grid was obtained with a geospatial analysis
      considering large fire perimeters and individual residential structures located
      within the study area. We made these raster grids available to assist in the
      optimization of wildfire risk management plans within the study area and to help
      mitigate potential losses from catastrophic events.

PMID- 29349104
TI  - Dataset demonstrating effects of momentum transfer on sizing of current collector
      for lithium-ion batteries during laser cutting.
AB  - Material properties of copper and aluminum required for the numerical simulation
      are presented. Electrodes used for the (paper) are depicted. This study describes
      the procedures of how penetration depth, width, and absorptivity are obtained
      from the simulation. In addition, a file format extracted from the simulation to
      visualize 3D distribution of temperature, velocity, and melt pool geometry is
      presented.

PMID- 29349105
TI  - Draft genome sequence of Brevibacterium epidermidis EZ-K02 isolated from
      nitrocellulose-contaminated wastewater environments.
AB  - Brevibacterium spp. are aerobic, nonbranched, asporogenous, gram-positive, rod
      shaped bacteria which may exhibit a rod-coccus cycle when cells get older and can
      be found in various environments. Several Brevibacterium species have industrial
      importance and are capable of biotransformation of various contaminants. Here we
      describe the draft genome sequence of Brevibacterium epidermidis EZ-K02 isolated
      from nitrocellulose-contaminated wastewater environments. The genome comprises
      3,885,924 bp, with a G + C content of 64.2%. This whole genome shotgun project
      has been deposited at DDBJ/ENA/GenBank under the accession PDHL00000000.

PMID- 29349106
TI  - The wildland-urban interface raster dataset of Catalonia.
AB  - We provide the wildland urban interface (WUI) map of the autonomous community of
      Catalonia (Northeastern Spain). The map encompasses an area of some 3.21 million
      ha and is presented as a 150-m resolution raster dataset. Individual housing
      location, structure density and vegetation cover data were used to spatially
      assess in detail the interface, intermix and dispersed rural WUI communities with
      a geographical information system. Most WUI areas concentrate in the coastal belt
      where suburban sprawl has occurred nearby or within unmanaged forests. This
      geospatial information data provides an approximation of residential housing
      potential for loss given a wildfire, and represents a valuable contribution to
      assist landscape and urban planning in the region.

PMID- 29349107
TI  - Draft genome sequence of Xylaria sp., the causal agent of taproot decline of
      soybean in the southern United States.
AB  - The draft genome of Xylaria sp. isolate MSU_SB201401, causal agent of taproot
      decline of soybean in the southern U.S., is presented here. The genome assembly
      was 56.7 Mb in size with an L50 of 246. A total of 10,880 putative protein
      encoding genes were predicted, including 647 genes encoding carbohydrate-active
      enzymes and 1053 genes encoding secreted proteins. This is the first draft genome
      of a plant-pathogenic Xylaria sp. associated with soybean. The draft genome of
      Xylaria sp. isolate MSU_SB201401 will provide an important resource for future
      experiments to determine the molecular basis of pathogenesis.

PMID- 29349108
TI  - Spatially and temporally continuous estimates of annual total nitrogen deposition
      over North America, 1860-2013.
AB  - This report describes the North American Climate Integration and Diagnostics -
      Nitrogen Deposition Version 1 (NACID-NDEP1) database. The database contains
      estimates of annual total nitrogen (N) deposition for the purpose of supporting
      terrestrial ecosystem modelling in North America. It was constructed at 1-km
      resolution with coverage of Alaska, Canada, and the conterminous U.S., with
      continuous annual coverage from 1860 to 2013. Estimates were produced by
      acquiring and compiling best-available data sources: Wet N deposition was
      estimated from interpolation of monthly ammonium and nitrate concentration
      measurements and from grids of monthly precipitation. Dry N deposition was
      estimated from satellite measurements of ammonium and nitrogen oxides. Total N
      deposition for the pre-industrial era was derived from previous modelling
      studies. As these source datasets covered different time periods, several
      assumptions were required to produce a continuous record.

PMID- 29349109
TI  - Data collected in an integrated ecological survey of rotifer communities and
      corresponding environmental variables in the highly polluted Haihe River Basin,
      China.
AB  - Here we presented two datasets (biological and environmental datasets) collected
      in a comprehensive large geographical scale (approximately 1.1*105 km2) survey of
      rivers/streams in the Haihe River Basin (HRB), which has become the most polluted
      river basin in past two decades in China. The survey selected a total of 94
      representative sampling sites in the plain region of HRB, where environmental
      pollution is more severe than the mountain region. The biological dataset
      contains the information on the identified rotifer species and their abundance,
      while the environmental dataset provides the measured environmental variables at
      each sampling site. Based on this ecological survey, we identified a total of 91
      rotifer species and their abundance, as well as abundance of two crucial
      taxonomic groups on rotifers' food webs (i.e., protozoans and crustaceans), and
      also presented seven environmental variables, particularly those associated with
      nitrogen and phosphorus pollution.

PMID- 29349110
TI  - Data on assessment of groundwater quality for drinking and irrigation in rural
      area Sarpol-e Zahab city, Kermanshah province, Iran.
AB  - In present study 30 groundwater samples were collected from Sarpol-e Zahab area,
      Kermanshah province of Iran in order to assess the quality of groundwater in
      subjected area and determining its suitability for drinking and agricultural
      purposes. Also the variations in the quality levels of groundwater were compared
      over the years of 2015 and 2016. Statistical analyses including Spearman
      correlation coefficients and factor analysis display good correlation between
      physicochemical parameters (EC, TDS and TH) and Na+, Mg2+, Ca2+, Cl- and
      [Formula: see text] ionic constituents. Also in order to assess water quality for
      irrigation we used the United States Department of Agriculture (USDA)
      classification which is based on SAR for irrigation suitability assessment. In
      addition, the residual sodium carbonate (RSC), %Na, PI, KR, SSP, MH, EC
      characteristics were calculated for all samples and used for assessment of
      irrigation suitability. Based on these indicators, for every two years, the
      quality of water for agriculture is in good and excellent category. The Piper
      classification for hydro geochemical facies indicates that the water in the study
      area is of Ca-HCO3- type. However, the study of water hardness shows that more
      than 80% of samples are in hard and very hard water class. Therefore, there is a
      need for decisions to refine and soften the water.

PMID- 29349111
TI  - Slowly progressive chest rash in an elderly woman.

PMID- 29349112
TI  - An immunosuppressed man with an isolated necrotic plaque on the chest.

PMID- 29349113
TI  - Conjunctivitis, mucosal erosions, and moist cutaneous plaques.

PMID- 29349114
TI  - Evaluation of a new venous catheter blood draw device and its impact on specimen
      hemolysis rates.
AB  - Objectives: Blood collections from peripheral intravenous catheters offer several
      benefits to patients, including reduced needle punctures and patient discomfort,
      but they risk reducing the quality of blood specimens analyzed by the laboratory.
      In an effort to balance analytical quality of test results with patient-centered
      care initiatives, a needle-less blood collection device called PIVOTM was
      evaluated at two institutions. The primary objective of this study was to assess
      the ability of the PIVOTM device to provide high-quality blood specimens for
      laboratory testing compared to current blood collection methods. Methods: Blood
      specimens drawn using the PIVOTM device were prospectively flagged. A
      retrospective review was performed comparing the degree and rate of hemolysis for
      PIVOTM blood collections to both concurrent and historical hemolysis rates for
      other collection methods. Results: Approximately 7600 PIVOTM blood draws were
      performed across the two institutions. The hemolysis rates of samples collected
      with PIVOTM were evaluated using 2380 flagged collections, containing
      approximately 1200 test orders requiring hemolysis index measurements. The
      hemolysis rate of PIVOTM-flagged samples (1.8%) was statistically superior to the
      venipuncture and central line blood collection methods (3.3%), reducing the risk
      of hemolysis during a venous blood draw by 39%. Conclusions: PIVOTM collections
      facilitated improvement in the rate and degree of sample hemolysis when compared
      to venipuncture and central line blood collections. These findings suggest that
      PIVOTM is capable of delivering samples that are superior to current blood
      collection methods in terms of hemolysis rate as well as reducing the number of
      invasive venipunctures required for laboratory testing.

PMID- 29349116
TI  - Does an advantageous occupational position make women happier in contemporary
      Japan? Findings from the Japanese Study of Health, Occupation, and Psychosocial
      Factors Related Equity (J-HOPE).
AB  - Occupational position is one of the determinants of psychological health, but
      this association may differ for men and women depending on the social context. In
      contemporary Japanese society, occupational gender segregation persists despite
      increased numbers of women participating in the labour market, which may
      contribute to gender specific patterns in the prevalence of poor psychological
      health. The present study examined gender specific associations between
      occupational position and psychological health in Japan, and the potential
      mediating effects of job control and effort-reward imbalance in these
      associations. We used data obtained from 7123 men and 2222 women, aged between 18
      and 65 years, who participated in an occupational cohort study, the Japanese
      Study of Health, Occupation, and Psychosocial Factors Related Equity (J-HOPE),
      between 2011 and 2012. We used logistic regression to examine the association
      between occupational position and poor psychological health, adjusted for age,
      working hours, household income and education, as well as psychosocial work
      characteristics (job control and effort-reward imbalance). The prevalence of poor
      psychological health increased from manual/service occupations (23%) to
      professionals/managers (38%) among women, while it did not vary by occupational
      position among men. In women, the significant association between occupational
      position and psychological health was not explained by job control, but was
      attenuated by effort-reward imbalance. Our findings suggest that Japanese women
      in more advantaged occupational positions are likely to be at a greater risk for
      poor psychological health due to higher levels of effort-reward imbalance at
      work.

PMID- 29349115
TI  - Social connections and suicidal behaviour in young Australian adults: Evidence
      from a case-control study of persons aged 18-34 years in NSW, Australia.
AB  - Purpose: There is evidence that social isolation is a risk factor for suicide,
      and that social connections are protective. Only a limited number of studies have
      attempted to correlate the number of social connections a person has in their
      life and suicidal behaviour. Method: Two population-based case-control studies of
      young adults (18-34 years) were conducted in New South Wales, Australia. Cases
      included both suicides (n=84) and attempts (n=101). Living controls selected from
      the general population were matched to cases by age-group and sex. Social
      connections was the main exposure variable (representing the number of
      connections a person had in their life). Suicide and attempts as outcomes were
      modelled separately and in combination using conditional logistic regression
      modelling. The analysis was adjusted for marital status, socio-economic status,
      and diagnosis of an affective or anxiety disorder. Results: Following adjustment
      for other variables, those who had 3-4 social connections had 74% lower odds of
      suicide deaths or attempts (OR=0.26, 95% CI 0.08, 0.84, p=0.025), and those with
      5-6 connections had 89% lower odds of suicide deaths or attempts (OR=0.11 95% CI
      0.03, 0.35, p<0.001), compared to those with 0-2 social connections. With the
      number of social connection types specified as a continuous variable, the odds
      ratio was 0.39 per connection (95% CI 0.27, 0.56, p<0.001). Conclusions: A
      greater number of social connections was significantly associated with reduced
      odds of suicide or attempt. This suggests that suicide prevention initiatives
      that promote increased social connections at an individual, familial, and wider
      social levels might be effective.

PMID- 29349117
TI  - The double burden of malnutrition in Indonesia: Social determinants and
      geographical variations.
AB  - The presence of simultaneous under- and over-nutrition has been widely documented
      in low- and middle-income countries, but global nutritional research has seen
      only a few large-scale population studies from Indonesia. We investigate the
      social determinants as well as the geographical variations of under- and over
      nutrition in Indonesia using the largest public health study ever conducted in
      the country, the National Basic Health Research 2007 (N=645,032). Multilevel
      multinomial logistic regression and quantile regression models are fitted to
      estimate the association between nutritional status and a number of socio
      economic indicators at both the individual and district levels. We find that: (1)
      education and income reduce the odds of being underweight by 10-30% but at the
      same time increase those of overweight by 10-40%; (2) independent from the
      compositional effect of poverty, income inequality is detrimental to population
      health: a 0.1 increase in the Gini coefficient is associated with an 8-12%
      increase in the odds of an individual's being both under- and overweight; and (3)
      the effects that these determinants have upon nutritional status are not
      necessarily homogeneous along the continuum of body mass index. Equally
      important, our analysis reveals that there is substantial spatial clustering of
      areas with elevated risk of under- or over-nutrition across the 17,000-island
      archipelago. As of 2007, under-nutrition in Indonesia remains a 'disease of
      poverty', while over-nutrition is one of affluence. The income inequality
      accompanying Indonesia's economic growth may aggravate the dual burden of under-
      and over-nutrition. A more equitable economic policy and a policy that improves
      living standards may be effective for addressing the double burden.

PMID- 29349118
TI  - Assessing the relationship between dental appearance and the potential for
      discrimination in Ontario, Canada.
AB  - Poor oral health is influenced by a variety of individual and structural factors.
      It disproportionately impacts socially marginalized people, and has implications
      for how one is perceived by others. This study assesses the degree to which
      residents of Canada's most populated province, Ontario, recognize income-related
      oral health inequalities and the degree to which Ontarians blame the poor for
      these differences in health, thus providing an indirect assessment of the
      potential for prejudicial treatment of the poor for having bad teeth. Data were
      used from a provincially representative survey conducted in Ontario, Canada in
      2010 (n=2006). The survey asked participants questions about fifteen specific
      conditions (e.g. dental decay, heart disease, cancer) for which inequalities have
      been described in Ontario, and whether participants agreed or disagreed with
      various statements asserting blame for differences in health between social
      groups. Binary logistic regression was used to determine whether assertions of
      blame for differences in health are related to perceptions of oral health
      conditions. Oral health conditions are more commonly perceived as a problem of
      the poor when compared to other diseases and conditions. Among those who
      recognize that oral conditions more commonly affect the poor, particular
      socioeconomic and demographic characteristics predict the blaming of the poor for
      these differences in health, including sex, age, education, income, and political
      voting intention. Social and economic gradients exist in the recognition of, and
      blame for, oral health conditions among the poor, suggesting a potential for
      discrimination amongst socially marginalized groups relative to dental
      appearance. Expanding and improving programs that are targeted at improving the
      oral and dental health of the poor may create a context that mitigates
      discrimination.

PMID- 29349119
TI  - The effect of deworming on early childhood development in Peru: A randomized
      controlled trial.
AB  - Background: There is a knowledge gap on the effect of early childhood deworming
      on development in low- and middle-income countries. This evidence is important in
      the critical window of growth and development before two years of age. Methods: A
      randomized controlled trial of the benefit, and optimal timing and frequency, of
      deworming on development was conducted in Iquitos, Peru. Children were enrolled
      during routine 12-month growth and development visits and randomly allocated to:
      (1) deworming at the 12-month visit and placebo at the 18-month visit; (2)
      placebo at the 12-month visit and deworming at the 18-month visit; (3) deworming
      at the 12 and 18-month visits; or (4) placebo at the 12 and 18-month visits. The
      Bayley Scales of Infant Development III was used to assess cognitive, language
      and motor skills at the 12 and 24-month visits. One-way ANOVA analyses used an
      intention-to-treat approach. Results: Between September 2011 and June 2012, 1760
      children were enrolled. Attendance at the 24-month visit was 88.8% (n=1563). Raw
      scores on all subtests increased over 12 months; however, cognitive and
      expressive language scaled scores decreased. There was no statistically
      significant benefit of deworming, or effect of timing or frequency, on any of the
      development scores. Baseline height and weight and maternal education were
      associated with development scores at 24 months. Conclusions: After 12 months of
      follow-up, an overall benefit of deworming on cognition, language or fine motor
      development was not detected. Additional integrated child and maternal
      interventions should be considered to prevent developmental deficits in this
      critical period.

PMID- 29349120
TI  - Trajectories and predictors of alcohol consumption over 21 years of mothers'
      reproductive life course.
AB  - Introduction: Little is known about the patterns of women's alcohol consumption
      over their reproductive life course. This study identifies trajectories of
      alcohol consumption by mothers over 21 years of their reproductive life course
      and examines baseline predictors of these trajectories. Methods: Data were
      obtained from a prospective cohort study of 3715 women in Brisbane, Queensland,
      Australia over 21 years of follow-up. Women's alcohol consumption was measured by
      frequency and quantity of use across the surveys. Potential predictors and
      confounding variables were assessed at baseline. Group based-trajectory modelling
      was used to identify typical drinking trajectories over the maternal reproductive
      life course. Multinomial logistic regression was employed to examine predictors
      associated with these trajectories. Results: Four trajectories of alcohol
      consumption were indentified for mothers over the 21-year period. These
      trajectories included abstainers (11.9%), low-stable drinkers (58.0%), moderate
      escalating drinkers (25.3%), and heavy-escalating drinkers (4.8%). After
      adjustment for significant covariates, membership of the abstaining trajectory
      was predicted by lower family income, being married, and high frequency of church
      attendance while membership of the heavier-escalating trajectory was associated
      with women who were not currently married, never went church and had unhealthy
      lifestyle behaviours. Conclusions: Patterns of women's alcohol consumption
      exhibit a high level of stability for abstainers and women who drink at low
      levels. After the birth of their child, there are some changes in alcohol
      consumption for the moderate and heavy-escalating alcohol consumption groups. Low
      risk patterns of consumption are associated with variables which generally
      reflected a low risk behaviour lifestyle. Intervention programmes should
      particularly target women engaging in the heavy-escalating alcohol consumption
      group as this group increase their consumption shortly after the birth of their
      child. There is a need to understand more about the social and health
      consequences to mothers and their children of being in the moderate and heavy
      escalating drinking trajectory groups.

PMID- 29349121
TI  - Adherence to clinical preventive services guidelines: Population-based online
      randomized trial.
AB  - The Patient Protection and Affordable Care Act (ACA) addresses use of clinical
      preventive services relative to evidence-based guidelines by mandating that most
      health insurance plans provide coverage without cost-sharing for services that
      receive an A or B rating. However, knowledge about and positive attitudes towards
      guidelines are extremely low. This study was a population-based randomized
      experiment to examine beliefs about and intentions to adhere to screening
      guidelines for the Prostate Specific Antigen (PSA) and Pap tests. The study had
      two objectives: (1) test reactions to and understanding of guidelines, and (2)
      experimentally compare receptivity to messages to promote PSA and Pap test
      recommendations. We first surveyed a population-based sample of (1) US adults age
      18 and over, (2) subsample of women aged 65 or younger, (3) subsample of men aged
      40 or older. A sample of 2923 completed an initial questionnaire. Next a subset
      of participants meeting eligibility criteria were recruited from the population
      based sample into a message testing experiment: (1) women aged 65 or younger, (2)
      and men aged 40 or older. Participants meeting these eligibility requirements
      were randomized to gain, loss, or balanced PSA (men) or Pap test (women) message
      stimulus conditions and followed for 8 weeks. Data were collected through the GfK
      Custom Research panel. A total of 2401 were eligible, 2321 completed the
      baseline, and 1730 completed follow up. Mixed effect regression models revealed
      that higher receptivity to messages was associated with greater intentions to
      seek cancer information and to speak to a Doctor about PSA and Pap tests. The
      loss frame was associated with higher intentions to speak to friends and family
      about PSA and Pap tests. Finally, perceived importance and personal understanding
      of guidelines predicted intentions to seek more information about them. This
      study contributes to evidence on how best to inform and engage consumers
      regarding preventive services.

PMID- 29349122
TI  - Fast food restaurant locations according to socioeconomic disadvantage, urban
      regional locality, and schools within Victoria, Australia.
AB  - Features of the built environment provide opportunities to engage in both healthy
      and unhealthy behaviours. Access to a high number of fast food restaurants may
      encourage greater consumption of fast food products. The distribution of fast
      food restaurants at a state-level has not previously been reported in Australia.
      Using the location of 537 fast food restaurants from four major chains
      (McDonald's, KFC, Hungry Jacks, and Red Rooster), this study examined fast food
      restaurant locations across the state of Victoria relative to area-level
      disadvantage, urban-regional locality (classified as Major Cities, Inner
      Regional, or Outer Regional), and around schools. Findings revealed greater
      locational access to fast food restaurants in more socioeconomically
      disadvantaged areas (compared to areas with lower levels of disadvantage), nearby
      to secondary schools (compared to primary schools), and nearby to primary and
      secondary schools within the most disadvantaged areas of the major city region
      (compared to primary and secondary schools in areas with lower levels of
      disadvantage). Adjusted models showed no significant difference in location
      according to urban-regional locality. Knowledge of the distribution of fast food
      restaurants in Australia will assist local authorities to target potential policy
      mechanisms, such as planning regulations, where they are most needed.

PMID- 29349123
TI  - Mortality among white, black, and Hispanic male and female state prisoners, 2001
      2009.
AB  - Although much research considers the relationship between imprisonment and
      mortality, little existing research has tested whether the short-term mortality
      advantage enjoyed by prisoners extends to Hispanics. We compared the mortality
      rates of non-Hispanic white, non-Hispanic black, and Hispanic male and female
      state prisoners to mortality rates in the general population using data from the
      Deaths in Custody Reporting Program, the National Prisoner Statistics, the
      National Corrections Reporting Program, and the Centers for Disease Control and
      Prevention. The results indicate that the mortality advantage for prisoners was
      greatest for black males, followed by black females, Hispanic males, white
      females, and white males. Hispanic female prisoners were the only group not at a
      mortality advantage relative to the general population, with an SMR of 1.18 [95%
      CI: 0.93-1.43]. Taken together, the results suggest that future research should
      seek to better understand the curious imprisonment-mortality relationship among
      Hispanic females, although given the small number of inmate deaths that happen to
      this group (~0.6%), this research should not detract from broader research on
      imprisonment and mortality.

PMID- 29349124
TI  - More than just numbers: Suicide rates and the economic cycle in Portugal (1910
      2013).
AB  - Suicides are a major concern for public health first and foremost because they
      are an avoidable cause of death. Moreover, they can be an indicator of self
      reported emotional satisfaction and a good marker of overall well-being. In this
      study we examine how different economic and social aspects affected Portuguese
      suicide rates for more than one hundred years (1910-2013). We place this exercise
      in the specific historical context of the XX and early XXI century in Portugal,
      emphasizing the role of economic recessions and expansions. Controlling for
      aspects like wars, health care availability, political instability, and
      demographic changes, we find a strong association between a decline in the growth
      rate of real output and an increase in suicide rates for the whole population. In
      this regard, while male suicide rates are non-negligibly influenced by economic
      downturns, female suicide rates are in general more responsive to a more open
      political and economic environment. Our results are robust if we consider the mid
      term cyclical relationship. Our findings advocate that, during recessions, public
      health responses should be seen as a crucial component of suicide prevention.

PMID- 29349126
TI  - La desesperacion in Latino migrant day laborers and its role in alcohol and
      substance-related sexual risk.
AB  - The purpose of this study was to better understand the relation between
      psychological distress and alcohol and substance related sexual risk in Latino
      migrant day laborers (LMDLs). In addition to examining the roles of depression
      and anxiety, it was also necessary to examine the role of desesperacion, a
      popular Latino idiom of distress frequently expressed by LMDLs in response to the
      thwarting of major migration related life goals such as traveling to the U.S. in
      search of work to support families, projects and purchases in country of origin.
      Given the structural vulnerability of LMDLs to under-employment and frequent
      unemployment, LMDLs also refer to desesperacion as a prelude to problem drinking,
      substance use, and sexual risk taking. Hence we developed and validated a scale
      of desesperacion for LMDLs to explore this culturally relevant construct of
      psychological distress in this unique population of Latinos. Based on a cross
      sectional survey of 344 LMDLs, this study found that the dissatisfaction subscale
      of desesperacion predicted alcohol-related sexual risk taking, while depression
      predicted substance-related sexual risk taking. These findings are discussed
      including implications of preventing alcohol and substance related sexual risk
      taking in LMDLs.

PMID- 29349125
TI  - Built environment assessment: Multidisciplinary perspectives.
AB  - Context: As obesity has become increasingly widespread, scientists seek better
      ways to assess and modify built and social environments to positively impact
      health. The applicable methods and concepts draw on multiple disciplines and
      require collaboration and cross-learning. This paper describes the results of an
      expert team's analysis of how key disciplinary perspectives contribute to
      environmental context-based assessment related to obesity, identifies gaps, and
      suggests opportunities to encourage effective advances in this arena. Evidence
      acquisition: A team of experts representing diverse disciplines convened in 2013
      to discuss the contributions of their respective disciplines to assessing built
      environments relevant to obesity prevention. The disciplines include urban
      planning, public health nutrition, exercise science, physical activity research,
      public health and epidemiology, behavioral and social sciences, and economics.
      Each expert identified key concepts and measures from their discipline, and
      applications to built environment assessment and action. A selective review of
      published literature and internet-based information was conducted in 2013 and
      2014. Evidence synthesis: The key points that are highlighted in this article
      were identified in 2014-2015 through discussion, debate and consensus-building
      among the team of experts. Results focus on the various disciplines' perspectives
      and tools, recommendations, progress and gaps. Conclusions: There has been
      significant progress in collaboration across key disciplines that contribute to
      studies of built environments and obesity, but important gaps remain. Using
      lessons from interprofessional education and team science, along with
      appreciation of and attention to other disciplines' contributions, can promote
      more effective cross-disciplinary collaboration in obesity prevention.

PMID- 29349127
TI  - Rollout of community-based family health strategy (programa de saude de familia)
      is associated with large reductions in neonatal mortality in Sao Paulo, Brazil.
AB  - Rationale: Several recent studies suggest that Brazil's Estrategia Saude de
      Familia (Family Health Strategy-FHS) has contributed to declines in mortality at
      the national and regional level. Comparatively little is known whether this
      approach is effective in urban populations with relatively easy access to health
      services. Objectives: To use detailed medical data collected as part of Sao
      Paulo's Western Region project to examine whether the FHS program had an impact
      on child health in Sao Paulo, Brazil. Results: No associations were found between
      FHS and birth weight (OR 1.03, 95% CI 0.93-1.29), gestational length (OR 0.98,
      95% CI 0.83-1.15) or stillbirth (OR 1.51, 95% CI 0.75-3.03). FHS eligibility was
      associated with a 42% reduction in the odds of child mortality (OR 0.58, 95% CI
      0.34, 0.91), with largest effect sizes for the early neonatal period (OR 0.18,
      95% CI 0.04-0.79). Conclusions: Community based health delivery platforms may be
      a highly effective way to reduce neonatal mortality in urban areas of low and
      middle income countries, even when access to general health services is almost
      universal.

PMID- 29349128
TI  - Self-efficacy is associated with increased food security in novel food pantry
      program.
AB  - We examined the effect of a novel food pantry intervention (Freshplace) that
      includes client-choice and motivational interviewing on self-efficacy and food
      security in food pantry clients. The study was designed as a randomized control
      trial. Participants were recruited over one year from traditional food pantries
      in Hartford, CT. Participants were randomized to Freshplace or traditional food
      pantries (controls) and data collection occurred at baseline with quarterly
      follow-ups for 18 months. Food security was measured using the USDA 18-item Food
      Security Module. A newly developed scale was utilized to measure self-efficacy.
      Scale reliability was measured using a Cronbach alpha test; validity was measured
      via correlating with a related variable. Analyses included chi-square tests for
      bivariate analyses and hierarchical linear modeling for longitudinal analyses. A
      total of 227 adults were randomized to the Freshplace intervention (n=112) or
      control group (n=115). The overall group was 60% female, 73% Black, mean age=51.
      The new self-efficacy scale showed good reliability and validity. Self-efficacy
      was significantly inversely associated with very low food security (p<.05). Being
      in the Freshplace intervention (p=.01) and higher self-efficacy (p=.04) were
      independently associated with decreased very low food security. The traditional
      food pantry model fails to recognize the influence of self-efficacy on a person's
      food security. A food pantry model with client-choice, motivational interviewing
      and targeted referral services can increase self-efficacy of clients.
      Prioritizing the self-efficacy of clients over the efficiency of pantry
      operations is required to increase food security among disadvantaged populations.

PMID- 29349129
TI  - Improving but unequal: Temporal trends in Chinese self-rated health, 1990-2012.
AB  - This study examines temporal trends in the self-rated health of Chinese adults
      from 1990 to 2012. Concentration on this particular period in Chinese history
      provides insights into the health implications of China's massive societal
      transformation induced by economic reform. A series of cross-classified random
      effects models were estimated predicting favorable health status across time
      periods and adjusted for age, cohort effect and individual-level covariates.
      Results show that more recent birth cohorts exhibit better health conditions than
      earlier birth cohorts. However, period effects had a more profound effect than
      that of birth cohort. Net of age, cohort and individual-level covariates, there
      is a significant and increasing trend in self-rated health since the early 1990s.
      The period pattern was non-monotonic, with health improvement in the early 1990s,
      a dip later in that decade, but more evidence of improvement by 2012. We also
      found that health disparities have widened over the past 20 years, particularly
      on the basis of income and educational attainment.

PMID- 29349130
TI  - The Hispanic health paradox: New evidence from longitudinal data on second and
      third-generation birth outcomes.
AB  - This study examines the birth weight of second and third-generation Hispanics
      born in California and Florida, two of the major immigrant destination states in
      the US. I exploit a unique dataset of linked birth records for two generations of
      children born in California and Florida (1970-2009) and linear probability models
      to investigate the generational decline in the birth outcomes of Hispanics in the
      US. The data allow using an extensive set of socio-demographic controls and
      breaking down the results by country of origin. Second-generation children of
      Mexican and Cuban origin have better birth outcomes than children of US-born
      white women. Children of Puerto Rican origin have instead worse birth outcomes.
      The advantage observed among second-generation Hispanics erodes substantially in
      the third generation but third-generation Mexicans retain some of it.

PMID- 29349131
TI  - Predictors of patient's intentions to participate in pragmatic clinical trials:
      An initial exploration.
AB  - The Veterans Health Administration is implementing a pragmatic trial research
      program, called Point of Care Research (POC-R). The purpose of this telephone
      survey in which respondents were randomized to different framing conditions of
      the purpose of POC-R was to determine the impact of differing frames of the
      purpose of POC-R on attitudes towards the program and intentions to participate;
      and the relative importance of different beliefs and attitudes in discriminating
      low vs. high intenders to participate in POC-R. The survey addressed veterans'
      perceptions and attitudes towards POC-R, and their willingness to participate in
      a pragmatic trial. Overall, respondents felt positively towards POC-R and
      intended to participate. Differing frames of the purpose of POC-R were not
      associated with either attitudes (towards the program) or intentions to
      participate. However, specific beliefs and attitudes toward POC-R program were
      predictive of intentions to participate.

PMID- 29349132
TI  - Why is multiple micronutrient powder ineffective at reducing anaemia among 12-24
      month olds in Colombia? Evidence from a randomised controlled trial.
AB  - In Colombia's bottom socio-economic strata, 46.6% of children under two are
      anaemic. A prevalence of above 20% falls within the WHO guidelines for daily
      supplementation with multiple micronutrient powder (MNP). To evaluate the effect
      of daily MNP supplementation on anaemia amongst Colombian children aged 12-24
      months we ran a cluster RCT (n=1440). In previous work, we found the intervention
      had no impact on haemoglobin or anaemia in this population. In this current
      paper, we investigate this null result and find it cannot be explained by an
      underpowered study design, inaccurate measurements, low adoption of and
      compliance with the intervention, or crowding out through dietary substitution.
      We conclude that our intervention was ineffective at reducing rates of childhood
      anaemia because MNP itself was inefficacious in our population, rather than poor
      implementation of or adherence to the planned intervention. Further analysis of
      our data and secondary data suggests that the evolution with age of childhood
      anaemia in Colombia, and its causes, appear different from those in settings
      where MNP has been effective. Firstly, rates of anaemia peak at much earlier ages
      and then fall rapidly. Secondly, anaemia that remains after the first year of
      life is relatively, and increasingly as children get older, unrelated to iron
      deficiency. We suggest that factors during gestation, birth, breastfeeding and
      early weaning may be important in explaining very high rates of anaemia in early
      infancy. However, the adverse effects of these factors appear to be largely
      mitigated by the introduction of solid foods that often include meat. This
      renders population wide MNP supplementation, provided after a diet of solid foods
      has become established, an ineffective instrument with which to target Colombia's
      childhood anaemia problem.

PMID- 29349133
TI  - Adverse outcomes in bereaved mothers: The importance of household income and
      education.
AB  - Intense and enduring psychological distress has been well-documented in numerous
      studies on bereaved parents including anxious, depressive, and traumatic stress
      symptoms. A state of poverty is also known to increase the risk of psychological
      distress in the general population, yet this variable has not yet been
      sufficiently evaluated in outcomes specifically for bereaved parents. This study
      is the first to investigate poverty, education, and parental bereavement while
      examining the relative risk of other variables as informed by the literature. The
      findings reveal that poverty was the strongest predictor of psychological
      distress when compared to others factors which have traditionally been considered
      significant in parental bereavement. Bereaved parents living in poverty may be
      less likely to seek support and have fewer available resources. Practice and
      policy implications are discussed.

PMID- 29349134
TI  - Influence of volunteer-led net step exercise class on older people's self-rated
      health in a depopulated town: A longitudinal study.
AB  - In a depopulated region where population aging is advancing, it is necessary to
      establish a method so local residents themselves can be actively involved in
      older people's health promotion. Net Step Exercise, a novel dual-task walking
      program, introduced residents to opportunities for physical activities and social
      participation without any health specialist support. In one depopulated town
      (Ikeda, Nakagawa-gun, Hokkaido, Japan), volunteer residents have held Net Step
      Exercise classes throughout the town since 2007. We longitudinally examined the
      influence of volunteer-led Net Step Exercise class participation on subsequent
      self-rated health in all individuals aged 70-79 years living in Ikeda. A total of
      662 people who completed a baseline mail-in questionnaire survey in 2012 were
      followed until 2014. Logistic regression analysis was performed to examine the
      association with self-rated health after two years of class participation once a
      month or more at baseline, after controlling for confounds such as age, sex,
      years of education, living alone, baseline self-rated health, regular exercise,
      and other physical activities. The odds ratio of poor self-rated health in older
      people who participated in classes was 0.53 (95% confidence interval [CI]: 0.34
      0.85) compared to older people not participating in classes. Even after
      confounding factors were adjusted, the odds ratio of class participation was 0.50
      (95% CI: 0.29-0.85). This study showed that participation in volunteer-led Net
      Step Exercise might prevent poor self-rated health. Such Net Step Exercise
      classes are a feasible method for older people's health promotion in depopulated
      municipalities.

PMID- 29349135
TI  - A life-course perspective on legal status stratification and health.
AB  - Scholars have expressed growing interest in the relationship between legal status
      stratification and health. Nevertheless, the extant research often lacks
      theoretical underpinnings. We propose the life-course perspective as a
      theoretical lens with which to understand relationships between legal status
      stratification and health outcomes. In particular, the life-course perspective
      guides researchers' attention to historical contexts that have produced
      differential social, political, and economic outcomes for immigrants based on
      legal status, and to the potentially long-term and intergenerational
      relationships between legal status stratification and health. We review four key
      dimensions of the life-course perspective and make recommendations for future
      directions in public health research on legal status and health.

PMID- 29349137
TI  - Premarital childbearing in sub-Saharan Africa: Can investing in women's education
      offset disadvantages for children?
AB  - Premarital childbearing is common in many parts of sub-Saharan Africa, and may
      become increasingly so with the rise in women's age at first marriage. These
      trends are concerning given the severe childhood health consequences associated
      with being born premaritally. However, women's could condition the experience of
      having a premarital birth in a way that lessens its consequences for children.
      Extending the large literature on the child health benefits of mothers' education
      including her educational attainment and acquisition of key educational skills -
      I analyze whether the consequences of being born premaritally are lessened among
      children whose mothers are more highly-educated. The study focuses on Malawi, a
      southeast African country where child mortality rates remain high. I use
      Demographic and Health Survey data to estimate discrete-time logistic regression
      models (N=30,411 children younger than age five) of the relationships between
      premarital childbearing, mothers' educational background, and child mortality.
      The findings confirm that though being born premaritally is associated with
      higher child mortality, this is only true for children whose mothers have never
      been to school or discontinued at the primary level and/or never learned how to
      read. There is no evidence that being born premaritally is associated with
      elevated mortality among children whose mothers have been to secondary school
      and/or know how to read. The results demonstrate that analyzing how premarital
      childbearing intersects with other sources of health inequality enhances our
      understanding of the circumstances under which it poses the greatest risk to
      child well-being in sub-Saharan Africa.

PMID- 29349136
TI  - Breast cancer presentation delays among Arab and national women in the UAE: a
      qualitative study.
AB  - Breast cancer (BC) is a disease that has improved prospects for survival if
      detected and treated early. Delayed help-seeking behavior, with poor survival as
      a consequence, is an important public health issue in the Middle East. More than
      75% of breast cancer patients in the United Arab Emirates (UAE) seek medical
      advice after experiencing a sign or symptom of the disease and many seek such
      advice late. Our aim was to explore factors influencing delayed presentation for
      treatment after self-discovery of symptoms consistent with breast cancer in Arab
      women in the United Arab Emirates (UAE), and to explore facilitators and barriers
      of women's health seeking behavior in the complex religiously dominated society
      of the UAE. A qualitative descriptive approach using semi-structured interviews
      was used. We interviewed nineteen BC survivors aged 35-70 who have experienced
      delayed presentation to treatment after symptomatic recognition of BC. The time
      interval between initial experience of symptoms consistent with BC, and taking
      action to seek medical help was between three months to three years. The key
      themes that emerged from the interviews were varying responses to symptom
      recognition, fear of societal stigmatization, and concerns regarding abandonment
      by spouse because of BC. Culture has a strong influence on the decisions of women
      in the UAE society. The lack of awareness about signs and symptoms of BC and
      routine screening has an important effect on symptom appraisal and subsequently
      decision making regarding options for treatment.

PMID- 29349138
TI  - Psychosocial job quality in a national sample of working Australians: A
      comparison of persons working with versus without disability.
AB  - Objectives: There is growing international policy interest in disability
      employment, yet there has been little investigation of job quality among people
      working with disability. This study uses Australian national data to compare the
      psychosocial job quality of people working with versus without disability.
      Methods: We used 10 annual waves of data from a large representative Australian
      panel survey to estimate the proportion of the population experiencing poorer
      psychosocial job quality (overall and by individual 'adversities' of low job
      control, high demands, high insecurity, and low fairness of pay) by disability
      status and impairment type. We used logistic regression to examine the pooled
      cross-sectional associations between disability and job quality, adjusting for
      age, sex, education and job type. Results: Those working with any disability
      showed approximately 25% higher odds of reporting one or more adversity at work
      (OR: 1.23, 95% CI: 1.15, 1.31), and this finding was consistent across impairment
      types with the exception of intellectual/developmental disability. Estimates were
      largely unchanged after adjustments. Similar results were found for reporting two
      or more adversities compared one or more. Conclusions: We observed that working
      people with a disability in Australia reported systematically poorer psychosocial
      job quality than those working without disability. These results suggest the need
      for further research to understand the reasons for these patterns, as well as
      policy and practice efforts to address this inequity.

PMID- 29349140
TI  - Working out what works: The case of midwife led care - Commentary on: Is model of
      care associated with infant birth outcomes among vulnerable women? A scoping
      review of midwifery-led versus physician-led care.

PMID- 29349139
TI  - Is model of care associated with infant birth outcomes among vulnerable women? A
      scoping review of midwifery-led versus physician-led care.
AB  - This scoping review investigates if, over the last 25 years in high resource
      countries, midwives' patients of low socioeconomic position (SEP) were at more or
      less risk of adverse infant birth outcomes compared to physicians' patients.
      Reviewers identified 917 records in a search of 12 databases, grey literature,
      and citation lists. Thirty-one full documents were assessed and nine studies met
      inclusion criteria. Eight studies were assessed as moderate in quality; one study
      was given a weak rating. Of the moderate quality studies, the majority found no
      statistical difference in outcomes according to model of care for preterm birth,
      low or very low birth weight, or NICU admission. No study reported a
      statistically significant difference for small for gestational age birth (2
      studies), or mean or low Apgar score (4 studies). However, one study found a
      reduced risk of preterm birth (AOR=0.70, p<0.01), and heavier mean infant birth
      weight (3325 g vs. 3282 g, p<0.01) for midwifery patients. Another study reported
      lower risk of low (RR=0.59, 95% CI: 0.46, 0.73) and very low birthweight
      (RR=0.44, 95% CI: 0.23, 0.85) for midwifery care. And, a third study reported a
      decrease in stays (1-3 days) in NICU (Adjusted Risk Difference=-1.8, 95% CI: 
      3.9, 0.2) for midwifery patients, though no overall difference in NICU admission
      of any duration. Other studies reported significant differences favoring
      midwifery care for mean birth weight (3598 g vs. 3407.3 g, p<0.05; 3233 g vs.
      3089 g, p<0.05; 2 studies) and very low birth weight (OR=0.35, 95% CI:0.1, 0.9),
      for sub-groups within the larger study populations. This scoping review
      documented heterogeneity in study designs and analytical methods, inconsistent
      findings, moderate methodological quality, and lack of currency. There is a need
      for new studies to definitively establish if and how a midwifery-led model of
      care influences birth outcomes for women of low SEP.

PMID- 29349141
TI  - Intraclass correlation values for adolescent health outcomes in secondary schools
      in 21 European countries.
AB  - Background: Cluster randomised controlled trials (CRCTs) are increasingly used to
      evaluate the effectiveness of interventions for improving health. A key feature
      of CRCTs is that individuals in clusters are often more alike than individuals in
      different clusters, irrespective of treatment. This similarity within clusters
      needs to be taken into account when planning CRCTs to obtain adequate sample
      sizes, and when analysing clustered data to obtain correct estimates. Methods:
      Nationally representative data from 15 to 16 year olds were analysed, from 21 of
      the 35 countries that participated in the 2007 European School Survey Project on
      Alcohol and Other Drugs. Within country school level intra-class correlation
      coefficients (ICCs) were calculated for substance use (self-reported alcohol use,
      regular alcohol use, binge drinking, any smoking, regular smoking, and illicit
      drug use) and psychosocial health (depressive mood and self-esteem). Unadjusted
      and adjusted ICCs are presented. ICCs are adjusted for student sex and
      socioeconomic status. Results: ICCs ranged from 0.01 to 0.21, with the highest
      (0.21) reported for regular smoking. Within country school level ICCs varied
      substantially across health outcomes, and among countries for the same health
      outcomes. Estimated ICCs were consistently higher for substance use (range 0.01
      0.21), than for psychosocial health (range 0.01-0.07). Within country ICCs for
      health outcomes varied by changes in the measurement of particular health
      outcomes, for example the ICCs for regular smoking (range 0.06-0.21) were higher
      than those for having smoked at all in the last month (range 0.03-0.17).
      Conclusions: For school level ICCs to be effectively utilised in informing sample
      size requirements for CRCTs and adjusting estimates from meta-analyses, the
      school level ICCs need to be both country and outcome specific.

PMID- 29349142
TI  - Towards an understanding of the structural determinants of oral health
      inequalities: A comparative analysis between Canada and the United States.
AB  - Objective: To compare the magnitude of, and contributors to, income-related
      inequalities in oral health outcomes within and between Canada and the United
      States over time. Methods: The concentration index was used to estimate income
      related inequalities in three oral health outcomes from the Nutrition Canada
      National Survey 1970-1972, Canadian Health Measures Survey 2007-2009, Health and
      Nutrition Examination Survey I 1971-1974, and National Health and Nutrition
      Examination Survey 2007-2008. Concentration indices were decomposed to determine
      the contribution of demographic and socioeconomic factors to oral health
      inequalities. Results: Our estimates show that over time in both countries,
      inequalities in decayed teeth and edentulism were concentrated among the poor and
      inequalities in filled teeth were concentrated among the rich. Over time,
      inequalities in decayed teeth increased and decreased for measures of filled
      teeth and edentulism in both countries. Inequalities were higher in the United
      States compared to Canada for filled and decayed teeth outcomes. Socioeconomic
      characteristics (education, income) contributed greater to inequalities than
      demographic characteristics (age, sex). As well, income contributed more to
      inequalities in recent surveys in both Canada and the United States. Conclusions:
      Inequalities in oral health have persisted over the past 35 years in Canada and
      the United States, and are associated with age, sex, education, and income and
      have varied over time.

PMID- 29349143
TI  - Changes in visitor profiles and activity patterns following dog supportive
      modifications to parks: A natural experiment on the health impact of an urban
      policy.
AB  - Urban parks are important settings for physical activity, but few natural
      experiments have investigated the influences of park modifications on activity
      patterns and visitor profiles.We assessed the impact of implementing a municipal
      policy on off-leash dogs in city parks in Calgary (Alberta, Canada). Systematic
      observation undertaken in 2011 and 2012 within four parks captured patterns of
      use, activities, and visitors' characteristics. After baseline data collection,
      off-leash areas were created in two parks only. We compared changes in the
      sociodemographic and activity profiles in all parks between 2011 and 2012.
      Visitors with dogs participated in less intense activity relative to visitors
      without dogs. In both modified parks, the intensity of children's activities
      decreased, while the intensity of adults' activities remained stable. Adjusting
      for visitor characteristics, the likelihood of dog-related visits, relative to
      other activities, significantly decreased in one of the two modified parks (odds
      ratio 0.55, p<.05). Accommodating off-leash dogs in parks has the potential to
      modify activities undertaken inside parks as well as the profile of visitors, but
      may not increase park visits among dog-walkers in the short term. Recreation,
      park, and urban planners and policy-makers need to consider the needs and
      preferences of the broader community in the design and redesign of public parks.

PMID- 29349144
TI  - Food and housing insecurity and health status among U.S. adults with and without
      prior military service.
AB  - Food and housing insecurity may contribute to poorer mental and physical health.
      It is unclear as to whether those with prior military service, compared to those
      without, are more vulnerable to these current stressors. The objective of this
      study was to use U.S. population-based data to determine whether prior military
      service moderates the association of food and housing insecurity with poor mental
      and physical health. We analyzed data from nine states administering the Social
      Context module from the 2011 and 2012 Behavioral Risk Factor Surveillance System.
      Multivariable logistic regression was used to examine the associations of housing
      and food insecurity with poor mental and physical health and potential
      modification by military service. Compared with those with a history of military
      service, those without had higher prevalence of food insecurity (23.1% versus
      13.7%) and housing insecurity (36.0% versus 22.5%). Food insecurity was
      associated with poor mental and physical health (mental health: odds ratio
      (OR)=3.47, 95% confidence interval (CI)=[3.18-3.77]; physical health: OR=3.21,
      95% CI=[2.92-3.53]). Similar associations were observed between housing
      insecurity and poor mental and physical health. Prior military service was
      significantly associated with poor physical health. Interaction terms of prior
      military service with food and housing were not statistically significant. Food
      and housing insecurity does not appear to differentially impact mental and
      physical health among those with and without military service.

PMID- 29349145
TI  - Residential environments, alcohol advertising, and initiation and continuation of
      alcohol consumption among adolescents in urban Taiwan: A prospective multilevel
      study.
AB  - Background: Research indicates that place characteristics and the media
      environment are important contextual determinants of underage drinking behaviors
      in Western countries, but it is unknown whether these exposures influence
      adolescent alcohol consumption outside Western contexts, including in Asia's
      emerging global alcohol markets. Guided by the social ecological framework, we
      prospectively investigated the influences of place characteristics and alcohol
      advertising on initiation and continuation of alcohol consumption among
      adolescents in Taipei, Taiwan. Methods: Data on individual-level characteristics,
      including alcohol use behaviors and perceived exposure to alcohol advertising,
      were obtained from two waves of a longitudinal school-based study through a
      stratified probability sampling method in 2010 (Grade 7/Grade 8, aged 13-14 years
      old) and 2011-2012 (Grade 9, aged 15 years old) from 1795 adolescents residing in
      22 of 41 districts in Taipei. Data on district-level characteristics were drawn
      from administrative sources and Google Street View virtual audit to describe
      districts where adolescents lived at baseline. Hierarchical generalized linear
      models tested hypotheses about the associations of place characteristics and
      perceived alcohol advertising with underage drinking, with stratification by
      baseline lifetime alcohol consumption. Results: Among alcohol-naive adolescents,
      lower district-level economic disadvantage, a higher proportion of betel nut
      kiosks (a relatively unregulated alcohol source) compared to off-premises alcohol
      outlets, and exposure to television-based alcohol advertising predicted increased
      likelihood of alcohol initiation at one-year follow-up. Among alcohol-experienced
      adolescents, greater spatial access to off-premises alcohol outlets, and lower
      access to metro rapid transportation (MRT) and to temples were found to predict a
      subsequent increased likelihood of continued alcohol use. Parental drinking
      moderated the relationship between district-level violent crime and initiation of
      alcohol consumption. Conclusions: These findings suggest that local social
      economic status, alcohol access, and institutional resource and individual media
      exposure affect underage drinking behaviors in Taiwan. We discuss potential
      public health implications for place-based interventions. Future research on
      place, media, and adolescent alcohol consumption in Asian contexts is warranted.

PMID- 29349146
TI  - Inpatient migration patterns in persons with spinal cord injury: A registry study
      with hospital discharge data.
AB  - This study investigated and compared patient migration patterns of persons with
      spinal cord injury, the general population and persons with morbid obesity,
      rheumatic conditions and bowel disease, for secondary health conditions, across
      administrative boundaries in Switzerland. The effects of patient characteristics
      and health conditions on visiting hospitals outside the residential canton were
      examined using complete, nationwide, inpatient health records for the years 2010
      and 2011. Patients with spinal cord injury were more likely to obtain treatment
      outside their residential canton as compared to all other conditions.
      Facilitators of patient migration in persons with spinal cord injury and the
      general hospital population were private or accidental health insurances covering
      costs. Barriers of patient migration in persons with spinal cord injury were old
      age, severe multimorbidity, financial coverage by basic health insurance, and
      minority language region.

PMID- 29349148
TI  - Assessing adolescent spiritual health and well-being (commentary related to
      Social Science & Medicine - Population Health, ref: SSMPH-D-15-00089).

PMID- 29349147
TI  - Developmental patterns of adolescent spiritual health in six countries.
AB  - The spiritual health of adolescents is a topic of emerging contemporary
      importance. Limited numbers of international studies provide evidence about
      developmental patterns of this aspect of health during the adolescent years.
      Using multidimensional indicators of spiritual health that have been adapted for
      use within younger adolescent populations, we therefore: (1) describe aspects of
      the perceptions of the importance of spiritual health of adolescents by
      developmental stage and within genders; (2) conduct similar analyses across
      measures related to specific domains of adolescent spiritual health; (3) relate
      perceptions of spiritual health to self-perceived personal health status. Cross
      sectional surveys were administered to adolescent populations in school settings
      during 2013-2014. Participants (n=45,967) included eligible and consenting
      students aged 11-15 years in sampled schools from six European and North American
      countries. Our primary measures of spiritual health consisted of eight questions
      in four domains (perceived importance of connections to: self, others, nature,
      and the transcendent). Socio-demographic factors included age, gender, and
      country of origin. Self-perceived personal health status was assessed using a
      simple composite measure. Self-rated importance of spiritual health, both overall
      and within most questions and domains, declined as young people aged. This
      declining pattern persisted for both genders and in all countries, and was most
      notable for the domains of "connections with nature" and "connections with the
      transcendent". Girls consistently rated their perceptions of the importance of
      spiritual health higher than boys. Spiritual health and its domains related
      strongly and consistently with self-perceived personal health status. While
      limited by the 8-item measure of perceived spiritual health employed, study
      findings confirm developmental theories proposed from qualitative observation,
      provide foundational evidence for the planning and targeting of interventions
      centered on adolescent spiritual health practices, and direction for the study of
      spiritual health in a general population health survey context.

PMID- 29349149
TI  - The relationship between relative deprivation and self-rated health among
      Palestinian women in refugee camps in Lebanon.
AB  - Background: Relative deprivation (RD) has been advanced as a theory to explain
      the relationship between income inequality and health in high-income countries.
      In this study, we tested the theory in a low-income protracted refugee setting in
      a middle-income country. Methods: Using data from the 2010 Socioeconomic Survey
      of Palestine Refugees in Lebanon, we examined the relationship between RD and
      health among a representative sample of Palestinian refugee women (N=1047). Data
      were gathered utilizing a household questionnaire with information on socio
      demographics and an individual-level questionnaire with information on the health
      of each respondent. We examined self-rated health (SRH) as the main health
      measure but also checked the sensitivity of our results using self-reported
      chronic conditions. We used two measures for absolute SES: total household
      monthly expenditures on non-food goods and services and total household monthly
      expenditures on non-health goods and services. With refugee camp as a reference
      group, we measured a household's RD as a household's rank of absolute SES within
      the reference group, multiplied by the distance between its absolute SES and the
      average absolute SES of all households ranked above it. We investigated the
      robustness of the RD-SRH relationship using these two alternative measures of
      absolute SES. Results: Our findings show that, controlling for absolute SES and
      other possible confounders, women report significantly poorer health when they
      live in households with a higher score on our RD measure (because of either lower
      relative rank or lower relative SES compared to households better off in the
      reference group which we take to be the refugee camp). While RD is always
      significant as a determinant of SRH under a variety of specifications, absolute
      SES is not consistently significant. These findings persist when we use self
      reported chronic conditions as our measure of health instead of SRH, suggesting
      that the relationship between health and RD may be operating through a
      psychosocial mechanism. Discussion: Our findings underscore the importance of
      examining RD under conditions of poverty and in diverse socio-cultural contexts.
      They also highlight that public health approaches should be concerned with
      reducing social inequalities in low-income settings in addition to alleviating
      poverty.

PMID- 29349150
TI  - Paradox and privilege: A 55-year follow-up of the mortality of Yale College
      graduates.
AB  - Objective: Two hypotheses were tested: 1. People from privileged backgrounds had
      better survival than those from less privileged backgrounds. 2. The advantages of
      privilege were vitiated by fraternity membership. Methods: A 55-year
      retrospective cohort study of survival since 1960 of 945 graduates of Yale
      College followed to 2015. Results: The survival of graduates of private secondary
      schools (the privileged group) did not differ from that of public school
      graduates. However, graduates of private secondary schools who had not joined a
      fraternity in college had significantly better survival than private school
      graduates who had joined fraternities and than public school graduates, whether
      fraternity members or not. Conclusions: The benefits of a privileged background
      in respect of survival were undermined by fraternity membership. It is suggested
      that both self-selection and substance mis-use may have contributed to the
      survival difference.

PMID- 29349151
TI  - Can socioeconomic factors explain geographic variation in overweight in Norway?
AB  - We explore if the geographic variation in excess body-mass in Norway can be
      explained by socioeconomic status, as this has consequences for public policy.
      The analysis was based on individual height and weight for 198,311 Norwegian
      youth in 2011, 2012 and 2013, stemming from a compulsory screening for military
      service, which covers the whole population aged seventeen. These data were merged
      with municipality-level socioeconomic status (SES) variables and we estimated
      both ecological models and two-level models with a random term at the
      municipality level. Overweight was negatively associated with income, education
      and occupation at municipality level. Furthermore, the municipality-level
      variance in overweight was reduced by 57% in females and 40% in males, when SES
      factors were taken into account. This suggests that successful interventions
      aimed at reducing socioeconomic variation in overweight will also contribute to
      reducing the geographic variation in overweight, especially in females.

PMID- 29349152
TI  - Cross-border ties and the reproductive health of India's internal migrant women.
AB  - The literature on how social ties influence sexual and reproductive health is
      well established; however, one significant limitation of this research is the
      influence of social ties to hometowns among migrant women. Drawing from cross
      border social ties literature, the objective of this study is to assess how cross
      border social ties influence use of family planning and institutional deliveries
      among internal migrant women in India. Cross-sectional data come from 711 migrant
      women living in slums in Uttar Pradesh, India. Multivariable logistic regression
      was used to assess odds of modern use of family planning and odds of
      institutional deliveries with cross-border tie indicators. Results suggest that
      higher cross-border ties were associated with 2.35 times higher odds of family
      planning use (p<0.1) and 2.73 times higher odds of institutional delivery
      (p<0.05). This study suggests that social ties to hometowns may serve as a
      protective factor, possibly through increased social support, to migrants in
      regards to reproductive decision-making and use of reproductive health services.
      Future studies should explore potential mechanisms for these findings.

PMID- 29349153
TI  - Inequalities in mental health and well-being in a time of austerity: Baseline
      findings from the Stockton-on-Tees cohort study.
AB  - Since 2010, the UK has pursued a policy of austerity characterised by public
      spending cuts and welfare changes. There has been speculation - but little actual
      research - about the effects of this policy on health inequalities. This paper
      reports on a case study of local health inequalities in the local authority of
      Stockton-on-Tees in the North East of England, an area characterised by high
      spatial and socio-economic inequalities. The paper presents baseline findings
      from a prospective cohort study of inequalities in mental health and mental
      wellbeing between the most and least deprived areas of Stockton-on-Tees. This is
      the first quantitative study to explore local mental health inequalities during
      the current period of austerity and the first UK study to empirically examine the
      relative contributions of material, psychosocial and behavioural determinants in
      explaining the gap. Using a stratified random sampling technique, the data was
      analysed using multi-level models that explore the gap in mental health and
      wellbeing between people from the most and least deprived areas of the local
      authority, and the relative contributions of material, psychosocial and
      behavioural factors to this gap. The main findings indicate that there is a
      significant gap in mental health between the two areas, and that material and
      psychosocial factors appear to underpin this gap. The findings are discussed in
      relation to the context of the continuing programme of welfare changes and public
      spending cuts in the UK.

PMID- 29349154
TI  - Spirituality, religiosity, aging and health in global perspective: A review.
AB  - Persistent population aging worldwide is focusing attention on modifiable factors
      that can improve later life health. There is evidence that religiosity and
      spirituality are among such factors. Older people tend to have high rates of
      involvement in religious and/or spiritual endeavors and it is possible that
      population aging will be associated with increasing prevalence of religious and
      spiritual activity worldwide. Despite increasing research on religiosity,
      spirituality and health among older persons, population aging worldwide suggests
      the need for a globally integrated approach. As a step toward this, we review a
      subset of the literature on the impact of religiosity and spirituality on health
      in later life. We find that much of this has looked at the relationship between
      religiosity/spirituality and longevity as well as physical and mental health.
      Mechanisms include social support, health behaviors, stress and psychosocial
      factors. We identify a number of gaps in current knowledge. Many previous studies
      have taken place in the U.S. and Europe. Much data is cross-sectional, limiting
      ability to make causal inference. Religiosity and spirituality can be difficult
      to define and distinguish and the two concepts are often considered together,
      though on balance religiosity has received more attention than spirituality. The
      latter may however be equally important. Although there is evidence that
      religiosity is associated with longer life and better physical and mental health,
      these outcomes have been investigated separately rather than together such as in
      measures of health expectancy. In conclusion, there is a need for a unified and
      nuanced approach to understanding how religiosity and spirituality impact on
      health and longevity within a context of global aging, in particular whether they
      result in longer healthy life rather than just longer life.

PMID- 29349155
TI  - Impact of falling on social participation and social support trajectories in a
      middle-aged and elderly European sample.
AB  - Whereas falls are frequent and traumatic events for the elderly, their long-term
      consequences in terms of the social lives of older fallers are understudied. This
      study aimed to identify the impact of falling on the trajectories of social
      participation and social support of older people in Europe. Our sample consisted
      of 16,583 people aged 50-95 years from 10 European countries who responded to the
      waves 1, 2 and 4 of the Survey of Health Ageing and Retirement in Europe. The
      impact of falling on the trajectories of social participation and social support
      was examined using generalised estimating equation (GEE) models. The effect of
      the interactions between falling and frailty and between falling and social
      support on social participation was assessed. Falls were negatively associated
      with social participation (OR=0.73, p<0.001) and positively associated with
      social support (OR=2.20, p<0.001). For social participation, this effect was
      moderated by frailty; the interaction term between frailty and fall highlighted
      the finding that frailty better explained the global trajectory of social
      participation compared with falling. Social support did not buffer the negative
      impact of falling on social participation. Falls can be considered stressful
      events that have implications beyond the health context. Frail people who have
      fallen should be targeted in prevention and rehabilitation programmes; specific
      attention should also be paid to the relatives of fallers, who appeared to be
      more intensively solicited after a fall.

PMID- 29349156
TI  - Association of partner, parental, and employment statuses with self-rated health
      among German women and men.
AB  - The association of partner, parental, and employment statuses with health is
      usually discussed in terms of either the multiple role burden hypothesis or the
      multiple role attachment hypothesis. The first hypothesis states that combining
      work and family roles increases the burden of responsibility, which in turn
      increases the pressure and stress associated with competing roles, leading to
      poorer health. The multiple role attachment hypothesis argues that multiple
      responsibilities provide attachment to broader networks, which then provide
      social support and resources that enhance health. We analyzed pooled data from
      the German Health Update carried out by the Robert Koch Institute in 2009, 2010,
      and 2012. The data were collected by computer-assisted telephone interviews. The
      sample comprised 28,086 people aged 30-54 years. The data were assessed with
      logistic regression analysis and interaction models. The gender-differentiated
      analysis of partnership, parenthood, and employment, after adjusting for social
      and demographic characteristics, revealed small interaction effects among all
      three social roles with self-rated health in women and men. Non-employment showed
      the strongest relationship with poor self-rated health. It was significantly
      associated with lower self-rated health in both men and women in most of the
      family arrangements. These associations were higher in men than in women.
      Furthermore, in all family arrangements, female part-time employees were as
      healthy as female fulltime employees. A more subtle association was found in men:
      the odds of reporting poorer self-rated health were greater among non-parents
      employed part time than among those employed full time, but lower than among
      those who were non-employed. Among fathers, part-time employees did not have
      statistically better health than full-time employees.The findings support
      somewhat the multiple role attachment hypothesis, rather than the multiple role
      burden hypothesis. Because employment has great importance for both women's and
      men's health, the compatibility of work and family roles should be improved.

PMID- 29349157
TI  - Political fragmentation and widening disparities in African-American and white
      mortality, 1972-1988.
AB  - Objective: During the 1970s and 1980s in the U.S., population movement, urban
      sprawl and urban governance reform led to a proliferation of local, autonomous
      jurisdictions. Prior literature examines how this creation of local governments,
      also referred to as political fragmentation, contributes to economic growth and
      social inequality. We examine the impact of political fragmentation on health
      equity by testing the hypothesis that the mortality disparity between whites and
      African-Americans varies positively with political fragmentation. Methods: We
      retrieved mortality data from the multiple cause-of-death file and calculated
      total number of local governments per 1000 residents in a county to measure the
      degree of political fragmentation. We focused on 226 U.S. counties with
      population size greater than 200,000 and restricted the analysis to four distinct
      periods with overlapping government and mortality data (1972-73, 1977-78, 1982
      83, and 1987-88). We applied generalized estimating equation methods that permit
      analysis of clustered data over time. Methods also controlled for the age
      structure of the population, reductions in mortality over time, and confounding
      by county-level sociodemographic variables. Results: Adjusted coefficients of
      fragmentation are positive and statistically significant for both whites (coef:
      2.60, SE: 0.60, p<0.001) and African-Americans (coef: 5.31, SE: 1.56, p<0.001).
      The two-fold larger positive coefficient for African-Americans than for whites
      indicates a greater racial disparity in mortality among more politically
      fragmented urban counties and/or time periods. Conclusions: From 1972 to 1988,
      political fragmentation in large urban counties moves positively with the
      racial/ethnic gap in mortality between whites and African-Americans. We discuss
      intervening mechanisms through which political fragmentation may
      disproportionately affect mortality among African-Americans.

PMID- 29349158
TI  - Financial hardship, mastery and social support: Explaining poor mental health
      amongst the inadequately employed using data from the HILDA survey.
AB  - Objective: This study analysed data from the Household Income and Labour Dynamics
      in Australia (HILDA) Survey to examine the relationship between employment status
      and mental health, and the mediating effects of financial hardship, mastery and
      social support. In addition, the study sought to explore the effects of duration
      of unemployment on mental health. Methods: The primary analysis used three waves
      of data from the HILDA Survey with 4965 young adult respondents. Longitudinal
      population-averaged logistic regression models assessed the association of
      employment status and mental health, including the contribution of mastery,
      financial hardship and social support in explaining this association between
      employment groups (unemployed vs. employed; under employed vs. employed).
      Sensitivity analyses utilised a fixed-effects approach and also considered the
      full-range of working-age respondents. Regression analysis was used to explore
      the effect of duration of unemployment on mental health. Results: Respondents'
      who identified as unemployed or underemployed were at higher risk of poor mental
      health outcomes when compared to their employed counterparts. This association
      was ameliorated when accounting for mastery, financial hardship and social
      support for the unemployed, and was fully mediated for the underemployed. The
      fixed-effects models showed the transition to unemployment was associated with a
      decline in mental health and that mastery in particular contributed to that
      change. The same results were found with a broader age range of respondents.
      Finally, the relationship between duration of unemployment and mental health was
      not linear, with mental health showing marked decline across the first 9 weeks of
      unemployment. Conclusions and implications: Mastery, social support and financial
      hardship are important factors in understanding the association of poor mental
      health with both unemployment and underemployment. Furthermore, the results
      suggest that the most deleterious effects on mental health may occur in the first
      two months of unemployment before plateauing. In order to prevent deterioration
      in mental health, these findings suggest intervention should commence immediately
      following job loss.

PMID- 29349159
TI  - HIV in Japan: Epidemiologic puzzles and ethnographic explanations.
AB  - Japan is widely perceived to have a low level of HIV occurrence; however, its HIV
      epidemics also have been the subject of considerable misunderstanding globally. I
      used a ground truthing conceptual framework to meet two aims: first, to determine
      how accurately official surveillance data represented Japan's two largest
      epidemics (urban Kansai and Tokyo) as understood and experienced on the ground;
      and second, to identify explanations for why the HIV epidemics were unfolding as
      officially reported. I used primarily ethnographic methods while drawing upon
      epidemiology, and compared government surveillance data to observations at
      community and institutional sites (459 pages of field notes; 175 persons
      observed), qualitative interviews with stakeholders in local HIV epidemics (n =
      32), and document research (n = 116). This revealed seven epidemiologic puzzles
      involving officially reported trends and conspicuously missing information.
      Ethnographically grounded explanations are presented for each. These included
      factors driving the epidemics, which ranged from waning government and public
      attention to HIV, to gaps in sex education and disruptive leadership changes in
      public institutions approximately every two years. Factors constraining the
      epidemics also contributed to explanations. These ranged from subsidized medical
      treatment for most people living with HIV, to strong partnerships between
      government and a well-developed, non-governmental sector of HIV interventionists,
      and protective norms and built environments in the sex industry. Local and
      regional HIV epidemics were experienced and understood as worse than government
      reports indicated, and ground-level data often contradicted official knowledge.
      Results thus call into question epidemiologic trends, including recent
      stabilization of the national epidemic, and suggest the need for revisions to the
      surveillance system and strategies that address factors driving and constraining
      the epidemics. Based upon its utility in the current study, ground truthing has
      value as a conceptual framework for research and shows promise for future
      theoretical development.

PMID- 29349160
TI  - Theoretical basis and explanation for the relationship between area-level social
      inequalities and population oral health outcomes - A scoping review.
AB  - This study was conducted to review the evidence on the association between area
      level social inequalities and population oral health according to type and extent
      of social theories. A scoping review was conducted of studies, which assessed the
      association between area-level social inequality measures, and population oral
      health outcomes including self-rated oral health, number of teeth, dental caries,
      periodontal disease, tooth loss, oral health-related quality of life (OHRQoL) and
      dental pain. A search strategy was applied to identify evidence on PubMed,
      MEDLINE (Ovid), EMBASE, Web of Science, ERIC, Sociological Abstracts, Social
      Services Abstracts, references of selected studies, and further grey literature.
      A qualitative content analysis of the selected studies was conducted to identify
      theories and categorize studies according to their theoretical basis. A total of
      2892 studies were identified with 16 included in the review. Seven types of
      social theories were used on 48 occasions within the selected studies including:
      psychosocial (n=13), behavioural (n=10), neo-material (n=10), social capital
      (n=6), social cohesion (n=4), material (n=3) and social support (n=2). Of the
      selected studies, four explicitly tested social theories as pathways from
      inequalities to population oral health outcomes, three used a theoretical
      construct, seven used theories for post-hoc explanation and two did not have any
      use of theory. In conclusion, psychosocial theories were used most frequently.
      Although theories were often mentioned, majority of these studies did not test a
      social theory.

PMID- 29349161
TI  - Does multilingualism affect the incidence of Alzheimer's disease?: A worldwide
      analysis by country.
AB  - It has been suggested that the cognitive requirements associated with bi- and
      multilingual processing provide a form of mental exercise that, through increases
      in cognitive reserve and brain fitness, may delay the symptoms of cognitive
      failure associated with Alzheimer's disease and other forms of dementia. We
      collected data on a country-by-country basis that might shed light on this
      suggestion. Using the best available evidence we could find, the somewhat mixed
      results we obtained provide tentative support for the protective benefits of
      multilingualism against cognitive decline. But more importantly, this study
      exposes a critical issue, which is the need for more comprehensive and more
      appropriate data on the subject.

PMID- 29349162
TI  - Neighbourhood social and built environment factors and falls in community
      dwelling canadian older adults: A validation study and exploration of structural
      confounding.
AB  - Older persons are vulnerable to the ill effects of their social and built
      environment due to age-related limitations in mobility and bio-psychological
      vulnerability. Falls are common in older adults and result from complex
      interactions between individual, social, and contextual determinants. We
      addressed two methodological issues of neighbourhood-health and social
      epidemiological studies in this analysis: (1) validity of measures of
      neighbourhood contexts, and (2) structural confounding resulting from social
      sorting mechanisms. Baseline data from International Mobility in Aging Study were
      used. Samples included community-dwelling Canadians older than 65 living in
      Kingston (Ontario) and St-Hyacinthe (Quebec). We performed factor analysis and
      ecometric analysis to assess the validity of measures of neighbourhood social
      capital, socioeconomic status, and the built environment and stratified tabular
      analyses to explore structural confounding. The scales all demonstrated good
      psychometric and ecometric properties. There was an evidence of the existence of
      structural confounding in this sample of Canadian older adults as some
      combinations of strata for the three neighbourhood measures had no population.
      This limits causal inference in studying relationships between neighbourhood
      factors and falls and should be taken into account in aetiological aging
      research.

PMID- 29349163
TI  - Making health information meaningful: Children's health literacy practices.
AB  - Children's health and wellbeing is high on the research and policy agenda of many
      nations. There is a wealth of epidemiological research linking childhood
      circumstances and health practices with adult health. However, echoing a broader
      picture within child health research where children have typically been viewed as
      objects rather than subjects of enquiry, we know very little of how, in their
      everyday lives, children make sense of health-relevant information. This paper
      reports key findings from a qualitative study exploring how children understand
      food in everyday life and their ideas about the relationship between food and
      health. 53 children aged 9-10, attending two socio-economically contrasting
      schools in Northern England, participated during 2010 and 2011. Data were
      generated in schools through interviews and debates in small friendship groups
      and in the home through individual interviews. Data were analysed thematically
      using cross-sectional, categorical indexing. Moving beyond a focus on what
      children know the paper mobilises the concept of health literacy (Nutbeam, 2000),
      explored very little in relation to children, to conceptualise how children
      actively construct meaning from health information through their own embodied
      experiences. It draws on insights from the Social Studies of Childhood (James and
      Prout, 2015), which emphasise children's active participation in their everyday
      lives as well as New Literacy Studies (Pahl and Rowsell, 2012), which focus on
      literacy as a social practice. Recognising children as active health literacy
      practitioners has important implications for policy and practice geared towards
      improving child health.

PMID- 29349164
TI  - The 2005 London terror attacks: An investigation of changes in psychological
      wellbeing and social capital pre- and post-attacks (2003-07)-A UK panel study.
AB  - The London public transport suicide bombings, which occurred on 7th July 2005,
      were described as the worst single terrorist atrocity on British soil to date.
      Past acts of terrorism have been associated with deterioration in population
      mental health. They may also negatively impact levels of social capital, which is
      considered a buffer against poor mental health outcomes. By employing panel data
      from the British Household Panel Survey and following the same individuals
      (NT=9287) three times over a five-year period (2003, 2005 and 2007), the aim of
      this longitudinal multilevel study was to investigate: (i) the impact of
      terrorism on individual-level social capital (generalised trust and social
      participation) across the UK; and (ii) the buffering effects of social capital on
      psychological wellbeing (GHQ-12). By comparing 2005 and 2007 covariate values
      (including the two social capital proxies) against their pre-terror baseline
      (2003) measurements in two separate multilevel logistic regression models, we
      examined the immediate and longer-term effects of the 2005 attacks on our GHQ-12
      outcome. Compared to baseline, generalised trust dropped from 44% to 36%
      immediately post-terror attacks in 2005, while local participation increased from
      45.8% to 47.5%. Social capital levels started to return to baseline levels by
      2007, yet both proxies maintained independent buffering effects against poor GHQ
      12 scores in years 2005 and 2007. From this empirical evidence, it seems that
      though generalised trust levels are negatively affected by acts of terrorism, the
      accompanying increase in local active participation may aid in the re
      establishment of societal norms and beliefs in later years. Decision makers
      should be aware that such atrocities may negatively impact on populations'
      generalised trust in the shorter-term. To safeguard against losing this buffer
      against poor mental health outcomes, local active participation should be
      encouraged.

PMID- 29349165
TI  - Trajectories of informal care and health.
AB  - The evidence of the impact of informal care provision on the health of carers
      presents a complex and contested picture, depending on the characteristics of the
      care studied, including its duration, which has been relatively short in previous
      research (up to 4 years). Drawing on data from the Office for National Statistics
      Longitudinal Study, a 1% sample of linked Census records for respondents in
      England and Wales (N=270,054), this paper contributes original insights on the
      impact of care provision on the carer's health ten years later. The paper
      explores differentials in self-reported health in 2011 between individuals
      according to their caring status at 2001 and 2011, and controlling for a range of
      demographic and socio-economic characteristics. The results show that individuals
      providing informal care in 2011 (regardless of carer status in 2001) exhibit
      lower odds of poor health in 2011 than those who did not provide care in both
      2001 and 2011. Taking the intensity of care into account, 'heavy' carers in 2001
      (i.e. caring for more than 20 h per week) who were not caring in 2011 show a
      higher likelihood of reporting poor health than non-carers, while those who were
      'heavy' carers in both 2001 and 2011 are around one-third less likely to report
      poor health at 2011 compared to non-carers (2001 and 2011). These findings
      provide new insights in relation to repeat caring and its association with the
      carer's health status, further contributing to our understanding of the complex
      relationship between informal care provision and the carer's health.

PMID- 29349166
TI  - The impacts of public mammography screening on the relationship between
      socioeconomic status and cancer stage.
AB  - This study aimed to investigate the relationship between socioeconomic inequality
      and mortality following the introduction of a public mammography screening
      program in Norway by exploring the role of change in stage distribution as the
      mechanism for differences before and after the introduction of the screening
      program. Attained education level was used as a measure of socioeconomic status
      in this population-based study. All women aged 50-69 years diagnosed with breast
      cancer from 1999-2008 and with follow-up data until the end of 2009 were
      included. The primary endpoint was all-cause mortality. The results of a
      mediation analysis indicated that the introduction of screening led to stage
      distribution related reductions of -5.6 (95% confidence interval = -6.7 to -4.5),
      -2.5 (-3.0 to -2.1), and -1.4 (-1.9 to -0.9) fewer deaths per 1000 women for with
      a primary school education, secondary school education, and university education,
      respectively. The study showed that stage distribution explained -5 (-5.9 to 
      4.1) fewer deaths among women with a university education and -2.4 (-2.9 to -2.0)
      fewer deaths among women with a secondary school education before program
      implementation when compared to the group with a primary school education. There
      were significant reductions in mortality due to stage distribution after program
      implementation with differences relative to women with primary school of -1.8 (
      2.2 to -1.4) and -0.7 (-0.9 to -0.5) fewer deaths in favor of women with
      university education and secondary school, respectively. The results indicate
      reduced importance of cancer stage as a reason for differences in mortality by
      socioeconomic status after the introduction of a public mammography program.

PMID- 29349167
TI  - The weaker sex? Vulnerable men and women's resilience to socio-economic
      disadvantage.
AB  - Sex differences in mortality vary over time and place as a function of social,
      health, and medical circumstances. The magnitude of these variations, and their
      response to large socioeconomic changes, suggest that biological differences
      cannot fully account for sex differences in survival. Drawing on a wide swath of
      mortality data across countries and over time, we develop a set of empiric
      observations with which any theory about excess male mortality and its correlates
      will have to contend. We show that as societies develop, M/F survival first
      declines and then increases, a "sex difference in mortality transition" embedded
      within the demographic and epidemiologic transitions. After the onset of this
      transition, cross-sectional variation in excess male mortality exhibits a
      consistent pattern of greater female resilience to mortality under socio-economic
      adversity. The causal mechanisms underlying these associations merit further
      research.

PMID- 29349168
TI  - Associations between physical health and depressive symptoms in Chinese older
      adults: Do neighborhood resources matter?
AB  - This is one of the first studies to examine the buffering effect of neighborhood
      resources, specifically leisure amenities and voluntary associations, on the
      relationship between poor physical health and depressive symptoms among older
      persons in China. Using data from the 2011 baseline survey of the China Health
      and Retirement Longitudinal Study, the analytical sample included 4715 older
      adults aged 60 and over nested in 446 neighborhoods. Two-level linear regression
      analyses were conducted in the urban (n=1225) and rural (n=3490) samples,
      respectively. We found that leisure amenities significantly reduced the effect of
      ADL limitations on depressive symptoms in urban older adults, and alleviated the
      effect of chronic conditions on depressive symptoms in rural older Chinese.

PMID- 29349169
TI  - Differences in neighborhood social cohesion and aerobic physical activity by
      Latino subgroup.
AB  - Previous research has examined the role of neighborhood social cohesion in
      physical activity outcomes; however, less is known about this relationship across
      Latino subgroups. The purpose of our study was to examine the association between
      neighborhood social cohesion and aerobic leisure-time physical activity (LTPA)
      among Latino adults and to determine whether these associations differ by Latino
      subgroup. We used cross-sectional 2013-2014 National Health Interview Survey
      (NHIS) data on Latinos originating from 5 countries/regions (i.e., Latinos of
      Puerto Rican, Mexican/Mexican-American, Cuban/Cuban-American, Dominican and
      Central or South American origin) aged >=18 years (n=11,126). Multivariable
      logistic regression models were used to estimate associations between self
      reported neighborhood social cohesion and meeting aerobic LTPA guidelines. Models
      were adjusted for age, sex, education, and acculturation. We also investigated
      whether associations varied by Latino subgroup. In adjusted models for all Latino
      adults, compared with those reporting low social cohesion, individuals who
      reported high social cohesion (Odds Ratio [OR]: 1.33; 95% Confidence Interval
      [CI]: 1.17-1.52) were significantly more likely to meet the aerobic physical
      activity guideline. When stratified by Latino subgroups, among Mexican/Mexicans
      Americans (OR: 1.39; 95% CI: 1.16, 1.66) and Cuban/Cuban Americans (OR: 1.73; 95%
      CI: 1.00, 2.97) high social cohesion was associated with meeting the aerobic
      activity guideline. Among Dominicans, those who reported medium social cohesion
      (OR: 0.52, 95% CI: 0.29, 0.93) were less likely to meet the aerobic activity
      guideline. When examining aerobic physical activity outcomes in the Latino
      population, the role of neighborhood social cohesion and the variability among
      Latino subgroups should be considered.

PMID- 29349170
TI  - The relationship between raising a child with a disability and the mental health
      of mothers compared to raising a child without disability in japan.
AB  - Objective: Previous studies conducted in Japan targeted only mothers who cared
      for children with disabilities, and lacked reference subjects, such as mothers of
      children without disabilities. The aim of this study was to examine the
      association between raising one or two children with a disability and maternal
      psychological distress compared to mothers of children without a disability, and
      to assess differences among partnered mothers living with grandparent(s),
      partnered mothers without grandparent(s), and single mothers. Methods: This study
      utilized data from the Comprehensive Survey of Living Conditions (CSLC) in 2010.
      We merged the data of the children (aged six and over), mothers, and fathers.
      This study obtained 33,739 study subjects as a triad of a child (33,110 children
      without disabilities and 629 children with disabilities), mother, and father. The
      Japanese version of Kessler 6 (K6) was used to assess the psychological distress
      of mothers. Multivariate logistic regression was performed to assess the
      independent association of a child with a disability on maternal psychological
      distress after controlling for the basic characteristics of the children,
      mothers, and households. Results: This study reported that raising one or two
      children with disabilities was significantly related to maternal psychological
      distress (odds ratio: 1.72 for one child, 2.85 for two children) compared to
      mothers of children without disability. After stratifying the analyses by family
      structure, significant associations remained among mothers in two-parent families
      but not for mothers in three-generation families and single mothers due to a
      small number of children with disabilities in these families. Conclusions: This
      study reported the significant association between raising a child with a
      disability and maternal psychological distress in comparison to mothers of
      children without disabilities. Attention should be paid to not only single
      mothers, but also partnered mothers in two-parent families who have a child with
      a disability. It is important for health professionals to focus on the mental
      health of every mother of a child with a disability and to assess their needs for
      psychological support.

PMID- 29349171
TI  - Health returns to education by family socioeconomic origins, 1980-2008: Testing
      the importance of gender, cohort, and age.
AB  - Recent studies find that health returns to education are elevated among those who
      come from disadvantaged families. These findings suggest that education may be a
      health resource that compensates or "substitutes" for lower parental
      socioeconomic status. Alternatively, some studies find support for a cumulative
      (dis)advantage perspective, such that educational health returns are higher among
      those who already were advantaged, widening initial health (dis)advantages across
      the life course. However, it remains unclear whether these findings are dependent
      on gender or cohort, and this is a fundamental oversight given marked differences
      between men and women in educational and health inequalities across the twentieth
      century. Drawing on national US data (1980-2002 General Social Survey with 2008
      National Death Index Link), I indeed find that the presence or strength of
      resource substitution or cumulative (dis)advantage depends upon health measure as
      well as gender and cohort. For self-rated health, cumulative (dis)advantage
      explains educational health disparities, but among men only. Cumulative
      (dis)advantage in avoiding fair or poor health is partly explained by cohort and
      age variation in health returns to education, and cumulative (dis)advantage in
      excellent health is more robust in earlier cohorts and at older ages. For
      mortality, resource substitution is instead supported, but for women only. Among
      those from disadvantaged families, educational mortality buffering increases with
      cohort but diminishes with age. Taken together, these findings confirm prior
      research showing that adult health inequalities linked to education depend on
      family background, and extend this work by demonstrating that the nature and
      extent of these dynamics differ considerably depending on the health outcome
      being assessed and on an individual's historical context, life course stage, and
      gender.

PMID- 29349172
TI  - The impact of work-related physical assaults on mental health among Japanese
      employees with different socioeconomic status: The Japan Work Stress and Health
      Cohort Study (JSTRESS).
AB  - Background: Work-related physical assaults or violence has severely impacted on
      the safety of the work environment and employees' mental health. The aim of the
      present study was to investigate the prevalence of physical assaults, the effect
      of socioeconomic status (SES) on it and depression associated with it in
      employees working at large companies. Methods: A total of 22,770 Japanese
      employees responded to a self-administered questionnaire including SES
      (educational status and occupational status), violence victimization, worksite
      social support and depression (response rate, 85%). The 12-month prevalence of
      physical assaults and depression was examined using a single question and the
      Center for Epidemiologic Studies Depression scale, respectively. Results: The
      prevalence of physical assaults was 1.8% both in males and females. Although the
      risk of exposure to physical assaults was 2-3 times higher in the blue-collar
      group than in the manager group, the association of exposure to physical assaults
      with depression was stronger in the manager and white-collar worker group
      (Prevalence ratio [PR]=2.1 in males; 1.8 in females) than in the blue-collar
      worker group (PR=1.7 in males; 1.5 in females) after adjusting demographic and
      occupational covariates. A similar pattern was observed for education in males;
      the association was stronger than in the lower education group (PR=2.1 and 1.8).
      Conclusions: Low SES is a risk factor of exposure to physical assaults, however,
      the association of physical assaults with depression was significantly greater
      among company employees of higher SES than those of lower SES.

PMID- 29349173
TI  - The impact of self-reported health and register-based prescription medicine
      purchases on re-employment chances: A prospective study.
AB  - In this paper, we investigate the influence of self-reported health and register
      based prescription medicine purchases on re-employment chances, and whether these
      health indicators measure similar aspects of health in this analysis. Data came
      from a 2006 Danish unemployment survey among a random sample of unemployed
      individuals enriched with register data (2006-2008, N=1806). The survey
      participants all received unemployment benefits from the welfare system and had
      been unemployed for more than 20 weeks at the time of the interview in 2006. We
      combined these data with longitudinal register data on individual prescription
      medicine purchases for somatic illnesses and prescription medicine purchases for
      mental illnesses, information on re-employment and various socio-demographic
      variables. We conducted binary logistic regression analyses to investigate the
      impact of self-reported health and prescription medicine purchases measured in
      2006 on re-employment chances in 2007 and 2008. Our analyses show that unemployed
      workers with poor self-reported health and workers who had prescription medicine
      purchases for mental illnesses were less likely to be re-employed in 2007 and
      2008. Furthermore, the impact of both prescription medicine purchases for somatic
      illnesses and for mental illnesses increased when adding self-reported health to
      the model although prescription purchases for somatic illnesses became
      statistically insignificant. The impact of prescription medicine purchases for
      somatic illnesses was mediated by self-reported health, whilst prescription
      medicine purchases for mental illnesses was only partly mediated. Finally, SRH
      seemed a much stronger prediction than prescription medicines. From these
      results, we propose, when possible, the inclusion of both an indicator of self
      reported health and an indicator of mental health in studies on re-employment.

PMID- 29349174
TI  - Self-identified race, socially assigned skin tone, and adult physiological
      dysregulation: Assessing multiple dimensions of "race" in health disparities
      research.
AB  - Despite a general acceptance of "race" as a social, rather than biological
      construct in the social sciences, racial health disparities research has given
      less consideration to the dimensions of race that may be most important for
      shaping persistent disparities in adult physical health status. In this study, we
      incorporate the social constructionist view that race is multidimensional to
      evaluate the health significance of two measures of race, racial self
      identification and the socially perceived skin tone of black Americans, in a
      sample of black and white adults in the Nashville Stress and Health Study
      (N=1186). First, we use the approach most common in disparities research
      comparing group differences in an outcome-to consider self-identified racial
      differences in allostatic load (AL), a cumulative biological indicator of
      physical dysregulation. Second, we examine intragroup variations in AL among
      blacks by skin tone (i.e. light, brown, or dark skin). Third, we assess whether
      the magnitude of black-white disparities are equal across black skin tone
      subgroups. Consistent with prior research, we find significantly higher rates of
      dysregulation among blacks. However, our results also show that racial
      differences in AL vary by blacks' skin tone; AL disparities are largest between
      whites and dark-skinned blacks and smallest between whites and light-skinned
      blacks. This study highlights the importance of blacks' skin tone as a marker of
      socially-assigned race for shaping intragroup and intergroup variations in adult
      physiological dysregulation. These results demonstrate the importance of
      assessing multiple dimensions of race in disparities research, as this approach
      may better capture the various mechanisms by which "race" continues to shape
      health.

PMID- 29349175
TI  - The development of a bridging social capital questionnaire for use in population
      health research.
AB  - Bridging social capital is defined as the connections between individuals who are
      dissimilar with respect to socioeconomic and other characteristics. There is an
      important gap in the literature related to its measurement. We describe the
      development and validation of a questionnaire to measure bridging social capital.
      We focused the development of the questionnaire to be suitable for use in Latino
      immigrant populations in the U.S. The structure of the questionnaire comprised
      the following: Socialization in the job place (5 items); Membership in community
      activities (16 items); Participation in community activities (5 items); Contact
      with similar/different people (7 items); Assistance (17 items); Trust of
      institutions, corporations and other people(14 items); and Trust of intimate
      people (3 items). First, we used focus groups (N=17 participants) to establish
      content validity with an inductive thematic analysis to identify themes and
      subthemes. Changes were made to the questionnaire based on difficulty,
      redundancy, length and semantic equivalence. Second, we analyzed the
      questionnaire's psychometric properties (N=138). We tested internal consistency
      with Cronbach alpha and construct validity with a Confirmatory Factor Analysis
      (CFA) for each sub-scale to test theoretical unity; discriminant validity to
      observe differences between participants from high and low SES backgrounds and
      different language; and content validity with an independent expert panel.
      Cronbach alphas ranged from 0.80 (Assistance) to 0.92 (Trust). CFA results
      indicated that CFI and TLI were higher than 0.90 in almost all the scales, with
      high factor loadings. The Wilcoxon tests indicated that there were statistically
      significant mean differences between SES and language groups (p<0.00). The
      independent expert panel determined that the questionnaire had good content
      validity. This is the first demonstration of a psychometrically validated
      questionnaire to measure bridging social capital in an immigrant population in
      the United States. Our questionnaire may be suitable for further refinement and
      adaptation to other immigrant groups in different countries.

PMID- 29349176
TI  - Do age, psychosocial, and health characteristics alter the weak and strong tie
      composition of network diversity and core network size in urban adults?
AB  - Social capital and social support are two key constructs in the study of social
      networks and health. Despite their importance, little research has sought to
      examine the characteristics of those social ties by which individuals access
      social capital and support resources. Network diversity - a key structural
      feature in accessing social capital - refers to a person's broad but generally
      weak and heterogeneous social ties; core network size - a key structural feature
      in accessing social support - refers to the close, strong ties in personal
      networks. Our study examines whether the tie strength composing network diversity
      and core network size varies according to age-, psychosocial-, or health-related
      characteristics. Data came from the Montreal Neighbourhood Networks and Healthy
      Aging (MoNNET-HA) study, a representative sample of 2707 Montreal, Canada adults.
      Position and name generators were used to collect data on network diversity and
      core networks, and whether access to social resources was through kin, friends,
      or acquaintances. Multilevel negative binomial regression was used to account for
      the counts of different tie strengths nested within individuals and tracts.
      Network diversity and core network size both declined with older age groups, with
      those declines being more noticeable in not having ties at all or fewer ties with
      friends. Psychosocial and health factors altered the relative contribution of
      kin, friends and acquaintances to network diversity and core network size in
      similar patterns. Understanding the tie composition of network diversity and core
      network size can contribute to our knowledge of the social mechanisms linking
      social capital and support to health outcomes.

PMID- 29349177
TI  - Contextual generalized trust and immunization against the 2009 A(H1N1) pandemic
      in the American states: A multilevel approach.
AB  - The aim of the study was to investigate the association between contextual
      generalized trust and individual-level 2009 A(H1N1) pandemic immunization
      acceptance. A second aim was to investigate whether knowledge about the A(H1N1)
      pandemic mediated the association between contextual generalized trust and
      A(H1N1) immunization acceptance. Data from the National 2009 H1N1 Flu Survey was
      used. To capture contextual generalized trust, data comes from an aggregation of
      surveys measuring generalized trust in the American states. To investigate the
      association between contextual generalized trust and immunization acceptance,
      while taking potential individual-level confounders into account, multilevel
      logistic regression was used. The investigation showed contextual generalized
      trust to be significantly associated with immunization acceptance. However,
      controlling for knowledge about the A(H1N1) pandemic did not substantially affect
      the association between contextual generalized trust and immunization acceptance.
      In conclusion, contextual state-level generalized trust was associated with
      A(H1N1) immunization, but knowledge about A(H1N1) was not mediating this
      association.

PMID- 29349178
TI  - Trends in socioeconomic inequalities in self-rated health, smoking, and physical
      activity of Japanese adults from 2000 to 2010.
AB  - Health disparities in Japan are attracting increasing attention. Temporal trends
      in health disparities should be continuously monitored using multiple indices of
      socioeconomic status (SES) and health-related outcomes. We explored changes in
      socioeconomic differences in the health of Japanese adults during 2000-2010. The
      data was taken from the Japanese General Social Surveys, the cross-sectional
      surveys for nationally representative samples of Japanese adults. We used 14,193
      samples (individuals of 20-64 years of age) in our analysis. We estimated age
      adjusted prevalence ratios of the lowest SES group in comparison with the highest
      SES group using Poisson regression models with robust error variance. Relative
      index of inequality (RII) and slope index of inequality (SII) were also
      calculated. We examined the changes in the association between health-related
      outcomes (self-rated health (SRH), smoking, and physical activity) and SES
      indices (income, education, occupation, and subjective social class
      identification). The results showed temporally expanding trends for the
      associations of current smoking with SES, especially among women, in both
      relative and absolute measures. In contrast, no expanding trends were seen for
      SRH and physical activity. Although the smoking rates declined through the first
      decade of the 21st century, the socioeconomic disparities in smoking prevalence
      among Japanese adults expanded, especially among women. Researchers and
      policymakers should continuously monitor the trends that may cause future
      disparities in smoking-related morbidity and mortality.

PMID- 29349179
TI  - Do flexicurity policies protect workers from the adverse health consequences of
      temporary employment? A cross-national comparative analysis.
AB  - Flexicurity policies comprise a relatively novel approach to the regulation of
      work and welfare that aims to combine labour market flexibility with social
      security. Advocates of this approach argue that, by striking the right balance
      between flexibility and security, flexicurity policies allow firms to take
      advantage of loose contractual arrangements in an increasingly competitive
      economic environment while simultaneously protecting workers from the adverse
      health and social consequences of flexible forms of employment. In this study, we
      use multilevel Poisson regression models to test the theoretical claim of the
      flexicurity approach using data for 23 countries across three waves of the
      European Social Survey. We construct an institutional typology of labour market
      regulation and social security to evaluate whether inequalities in self-reported
      health and limiting longstanding illness between temporary workers and their
      permanent counterparts are smaller in countries that most closely approximate the
      ideal type described by advocates of the flexicurity approach. Our results
      indicate that, while the association between temporary employment and health
      varies across countries, institutional configurations of labour market regulation
      and social security do not provide a meaningful explanation for this cross
      national variation. Contrary to the expectations of the flexicurity hypothesis,
      our data do not indicate that employment-related inequalities are smaller in
      countries that approximate the flexicurity approach. We discuss potential
      explanations for these findings and conclude that there remains a relative lack
      of evidence in support of the theoretical claims of the flexicurity approach.

PMID- 29349180
TI  - Neighborhood racial composition and poverty in association with pre-pregnancy
      weight and gestational weight gain.
AB  - Background: Studies of neighborhood racial composition or neighborhood poverty in
      association with pregnancy-related weight are limited. Prior studies of
      neighborhood racial density and poverty has been in association with adverse
      birth outcomes and suggest that neighborhoods with high rates of poverty and
      racial composition of black residents are typically segregated and systematically
      isolated from opportunities and resources. These neighborhood factors may help
      explain the racial disparities in pre-pregnancy weight and inadequate weight
      gain. This study examined whether neighborhood racial composition and
      neighborhood poverty was associated with weight before pregnancy and weight gain
      during pregnancy and if this association differed by race. Methods: We used vital
      birth records of singleton births of 73,061 non-Hispanic black and white women in
      Allegheny County, PA (2003-2010). Maternal race and ethnicity, pre-pregnancy body
      mass-index (BMI), gestational weight gain and other individual-level
      characteristics were derived from vital birth record data, and measures of
      neighborhood racial composition (percentage of black residents in the
      neighborhood) and poverty (percentage of households in the neighborhood below the
      federal poverty) were derived using US Census data. Multilevel log binomial
      regression models were performed to estimate neighborhood racial composition and
      poverty in association with pre-pregnancy weight (i.e., overweight/obese) and
      gestational weight gain (i.e., inadequate and excessive). Results: Black women as
      compared to white women were more likely to be overweight/obese before pregnancy
      and to have inadequate gestational weight gain (53.6% vs. 38.8%; 22.5% vs. 14.75
      respectively). Black women living in predominately black neighborhoods were
      slightly more likely to be obese prior to pregnancy compared to black women
      living in predominately white neighborhoods (PR 1.10; 95% CI: 1.03, 1.16). Black
      and white women living in high poverty areas compared with women living in lower
      poverty areas were more likely to be obese prior to pregnancy; while only white
      women living in high poverty areas compared to low poverty areas were more likely
      gain an inadequate amount of weight during pregnancy. Conclusions: Neighborhood
      racial composition and poverty may be important in understanding racial
      differences in weight among childbearing women.

PMID- 29349181
TI  - Indicators of subjective social status: Differential associations across race and
      sex.
AB  - Background: Subjective social status (SSS), or perception of rank on the social
      hierarchy, is an important indicator of various health outcomes. However, the
      psychosocial influences on this construct are unclear, and how these influences
      vary across different sociodemographic groups is poorly understood. Methods:
      Participants were 2077 African-American and Whites (M age=47.85; 57% female; 58%
      African American, and 58% above poverty) from the Healthy Aging in Neighborhoods
      of Diversity across the Life Span (HANDLS) study. Multiple regression analyses
      examined (1) hypothesized psychosocial indicators of SSS and (2) the moderating
      effect of race and sex on the variables associated with SSS. Results: In addition
      to the traditional measures of SES (i.e. income, employment, and education),
      psychosocial variables (i.e. depressive symptomatology, neighborhood
      satisfaction, and self-rated health) were significantly associated with SSS.
      However, some of these indicators varied with respect to race and sex. Three
      significant interactions were found: sex by employment, race by employment, and
      race by education, wherein objective measures of SES were more associated with
      SSS for Whites and men compared to African Americans and women. Conclusion:
      Psychosocial measures may influence individuals' perceptions of themselves on the
      social hierarchy. Additionally, SSS may vary by demographic group. When
      considering the impact of SSS on health, it is important to consider the unique
      interpretations that various demographic groups have when perceiving themselves
      on the social hierarchy.

PMID- 29349182
TI  - Life-course social and economic circumstances, gender, and resilience in older
      adults: The longitudinal International Mobility in Aging Study (IMIAS).
AB  - Although early socioeconomic adversity is associated with poorer function and
      health in adulthood, those who are able to adapt positively to such risks and
      threats develop a resilience that may ameliorate harm. Predictors of resilience
      have been examined in children, however exploring the relationship between life
      course events, lived environments and current resilience among older adults
      across countries is novel. We specifically studied how childhood social and/or
      economic adversity and current socioeconomic resources were associated with
      resilience in 2000 community dwelling older men and women in Canada, Colombia,
      Brazil and Albania. The longitudinal International Mobility in Aging Study
      (IMIAS) collected information in 2012 and 2014 on childhood adversity, current
      income sufficiency social support and social engagement, and resilience (Wagnild
      Resilience Scale RS-14). Resilience levels were moderately high, and similar
      among women and men. Early social adversity predicted later resilience for some,
      with women but not men adapting positively. In contrast there was no bouncing
      back from early economic adversity. Current social engagement aligned with
      resilience (women only) as did social support from children (for women) and
      friends (for men). Partner support was of no advantage to either. Among men
      economic circumstances were stronger correlates of resilience while for women
      social circumstances were primary. The impact of site on resilience suggested
      that cultural norms and values have an independent effect on resilience of their
      populations, with strong and positive social ties more typical of Latin America
      than Canada appearing to offset lower absolute incomes. These findings are of
      importance because resilience is dynamic, can be fostered across the lifespan and
      is generally associated with greater health. Understanding which social assets
      and resources can be reinforced to build individual resilience offers a means for
      decreasing the harms of social and economic adversity.

PMID- 29349183
TI  - The association between social cohesion and physical activity in canada: A
      multilevel analysis.
AB  - Although previous research has shown that social cohesion may promote physical
      activity, social cohesion at the individual level was not always differentiated
      from social cohesion at the community level, and studies were often limited to
      specific population subgroups or geographical areas. We addressed the above
      limitations through the use of a multilevel modelling approach and nationally
      representative data from the 2009-2014 Canadian Community Health Survey. Physical
      activity level was operationalized as average daily energy expenditure; social
      cohesion was assessed by self-rated sense of belonging to the local community;
      and communities were represented by Canada's Forward Sortation Areas. The sample
      included 245,150 respondents from 1570 communities. Geographical location was
      found to explain a significant proportion (4.1%) of the overall variance in
      physical activity level. After adjusting for age, sex, household income,
      education and urban-rural status, both individual- and community-level social
      cohesion were found to be positively associated with physical activity (p<0.001
      for both). Thus, efforts to promote social cohesion and integration within
      communities may also promote physical activity and overall health.

PMID- 29349184
TI  - Using photovoice methods to explore older people's perceptions of respect and
      social inclusion in cities: Opportunities, challenges and solutions.
AB  - Urbanisation and population ageing have contributed to recognise cities as
      important settings for healthy ageing. This paper considers opportunities,
      challenges and solutions of using photovoice methods for exploring how
      individuals perceive their cities and the contribution this makes to their
      health. It focuses on one aspect of older people's experiences - respect and
      social inclusion, in the context of a community-based participatory research.
      Drawing on selected findings (participants' photographs, associated quotes and
      researchers' field notes), we provide an assessment of the suitability of
      photovoice methodology for the intended purpose. Four groups of older people
      (n=26; aged 60 years or more) from four contrasting geographical areas in
      Liverpool, UK, were recruited purposively. Participants photographed perceived
      positive and negative aspects of respect and social inclusion in the city,
      reflecting on the meanings of the photographs in individual (n=23) and group
      interviews (n=9). Thematic and content analysis was conducted using NVivo 10
      software. The work reported here provides insights into how participants engage
      with the photovoice process; factors preventing taking photos of interest; and
      how photographs complement interviews and focus groups. The findings demonstrate
      that photovoice both facilitated the dissemination of personalised relevant
      knowledge, and encouraged critical dialogue between participants, and city
      stakeholders. Reported difficulties included photography of negative and social
      concepts, and anxiety when taking photographs due to (i) expectations of what is
      a 'proper' photograph, and (ii) the need to obtain consent from subjects. With
      preparation, training, and discussion of participants' ideas not expressed
      through photographs, photovoice was well-suited to this topic, providing insights
      complementing other research methods. Through analysing the application of
      photovoice for exploring perceptions of respect and social inclusion in cities,
      our paper has identified potential issues and provides important recommendations
      for researchers on how photovoice methodology can be strengthened in exploring
      conditions for better health in the urban environment.

PMID- 29349185
TI  - Differences in stroke and ischemic heart disease mortality by occupation and
      industry among Japanese working-aged men.
AB  - Occupation- and industry-based risks for stroke and ischemic heart disease may
      vary among Japanese working-aged men. We examined the differences in mortality
      rates between stroke and ischemic heart disease by occupation and industry among
      employed Japanese men aged 25-59 years. In 2010, we obtained occupation- and
      industry-specific vital statistics data from the Japanese Ministry of Health,
      Labour, and Welfare dataset. We analyzed data for Japanese men who were aged 25
      59 years in 2010, grouped in 5-year age intervals. We estimated the mortality
      rates of stroke and ischemic heart disease in each age group for occupation and
      industry categories as defined in the national census. We did not have detailed
      individual-level variables. We used the number of employees in 2010 as the
      denominator and the number of events as the numerator, assuming a Poisson
      distribution. We conducted separate regression models to estimate the incident
      relative risk for stroke and ischemic heart disease for each category compared
      with the reference categories "sales" (occupation) and "wholesale and retail"
      (industry). When compared with the reference groups, we found that occupations
      and industries with a relatively higher risk of stroke and ischemic heart disease
      were: service, administrative and managerial, agriculture and fisheries,
      construction and mining, electricity and gas, transport, and professional and
      engineering. This suggests there are occupation- and industry-based mortality
      risk differences of stroke and ischemic heart disease for Japanese working-aged
      men. These differences in risk might be explained to factors associated with
      specific occupations or industries, such as lifestyles or work styles, which
      should be explored in further research. The mortality risk differences of stroke
      and ischemic heart disease shown in the present study may reflect an excessive
      risk of Karoshi (death from overwork).

PMID- 29349186
TI  - The shape of the association between income and mortality in old age: A
      longitudinal Swedish national register study.
AB  - This study used data on the total population to examine the longitudinal
      association between midlife income and mortality and late-life income and
      mortality in an aging Swedish cohort. We specifically examined the shape of the
      associations between income and mortality with focus on where in the income
      distribution that higher incomes began to provide diminishing returns. The study
      is based on a total Swedish population cohort between the ages of 50 and 60 years
      in 1990 (n=801,017) followed in registers for up to 19 years. We measured
      equivalent disposable household income in 1990 and 2005 and mortality between
      2006 and 2009. Cox proportional hazard models with penalized splines (P-spline)
      enabled us to examine for non-linearity in the relationship between income and
      mortality. The results showed a clear non-linear association. The shape of the
      association between midlife (ages 50-60) income and mortality was curvilinear;
      returns diminished as income increased. The shape of the association between late
      life (ages 65-75) income and mortality was also curvilinear; returns diminished
      as income increased. The association between late-life income and mortality
      remained after controlling for midlife income. In summary, the results indicated
      that a non-linear association between income and mortality is maintained into old
      age, in which higher incomes give diminishing returns.

PMID- 29349187
TI  - An agent-based simulation of persistent inequalities in health behavior:
      Understanding the interdependent roles of segregation, clustering, and social
      influence.
AB  - Health inequalities are conspicuously persistent through time and often durable
      even in spite of interventions. In this study, I use agent-based simulation
      models (ABMs) to understand how the complex interrelationships between
      residential segregation, social network formation, group-level preferences, and
      social influence may contribute to this persistence. I use a more-stylized ABM,
      Bubblegum Village (BV), to understand how initial inequalities in bubblegum
      chewing behaviors either endure, increase, or decrease over time given group
      level differences in preferences, neighborhood-level barriers or facilitators of
      bubblegum chewing (e.g., access to bubblegum shops), and agents' preferences for
      segregation, homophily, and clustering (i.e., the 'tightness' of social
      networks). I further use BV to understand whether segregation and social network
      characteristics impact whether the effects of a bubblegum-reduction intervention
      that is very effective in the short term are durable over time, as well as to
      identify intervention strategies to reduce attenuation of the intervention
      effects. In addition to BV, I also present results from an ABM based on the
      distribution and social characteristics of the population in Philadelphia, PA.
      This model explores similar questions to BV, but examines racial/ethnic
      inequalities in soda consumption based on agents' social characteristics and
      baseline soda consumption probabilities informed by the 2007-2010 National Health
      and Nutrition Examination Survey. Collectively, the models suggest that
      residential segregation is a fundamental process for the production and
      persistence of health inequalities. The other major conclusion of the study is
      that, for behaviors that are subject to social influence and that cluster within
      social groups, interventions that are randomly-targeted to individuals with 'bad'
      behaviors will likely experience a large degree of recidivism to pre-intervention
      behaviors. In contrast, interventions that target multiple members of the same
      network, as well as multilevel interventions that include a neighborhood-level
      component, can reduce recidivism.

PMID- 29349188
TI  - Dietary quality in children and the role of the local food environment.
AB  - Diet is a modifiable contributor to many chronic diseases including childhood
      obesity. The local food environment may influence children's diet but this area
      of research is understudied. This study explores if distance to and the number of
      supermarkets and convenience stores in the local area around households are
      associated with dietary quality in nine year olds whilst controlling for
      household level socio-economic factors. This is a secondary analysis of Wave 1
      (2007/2008) of the Growing Up in Ireland (GUI) Child Cohort Study, a sample of
      8568 nine year olds from the Republic of Ireland. Dietary intake was assessed
      using a short, 20-item parent reported food frequency questionnaire and was used
      to create a dietary quality score (DQS) whereby a higher score indicated a higher
      diet quality. Socio-economic status was measured using household class, household
      income, and maternal education. Food availability was measured as road network
      distance to and the number of supermarkets and convenience stores around
      households. Separate fixed effects regression models assessed the association
      between local area food availability and dietary quality, stratified by sex. The
      DQS ranged from -5 to 25 (mean 9.4, SD 4.2). Mean DQS was higher in those who
      lived furthest (distance in quintiles) from their nearest supermarket (p<0.001),
      and in those who lived furthest from their nearest convenience store (p<0.001).
      After controlling for socio-economic characteristics of the household, there was
      insufficient evidence to suggest that distance to the nearest supermarket or
      convenience store was associated with dietary quality in girls or boys. The
      number of supermarkets or convenience stores within 1000 m of the household was
      not associated with dietary quality. Food availability had a limited effect on
      dietary quality in this study. Issues associated with conceptualising and
      measuring the food environment may explain the findings of the current study.

PMID- 29349189
TI  - Does employment security modify the effect of housing affordability on mental
      health?
AB  - This paper uses longitudinal data to examine the interrelationship between two
      central social determinants of mental health - employment security and housing
      affordability. Data from ten annual waves of the longitudinal Household, Income
      and Labour Dynamics in Australia (HILDA) survey (which commenced in 2000/1 and is
      ongoing) were analysed using fixed-effects longitudinal linear regression. Change
      in the SF-36 Mental Component Summary (MCS) score of working age individuals (25
      64 years) (51,885 observations of 10,776 people), associated with changes in
      housing affordability was examined. Models were adjusted for income, age, survey
      year, experience of serious injury/illness and separation/divorce. We tested for
      an additive interaction between the security of a household's employment
      arrangements and housing affordability. People in insecurely employed households
      appear more vulnerable than people in securely employed households to negative
      mental health effects of housing becoming unaffordable. In adjusted models,
      people in insecurely employed households whose housing became unaffordable
      experienced a decline in mental health (B=-1.06, 95% CI -1.75 to -0.38) while
      people in securely employed households experienced no difference on average. To
      progress our understanding of the Social Determinants of Health this analysis
      provides evidence of the need to bridge the (largely artificial) separation of
      social determinants, and understand how they are related.

PMID- 29349190
TI  - Barriers to uptake of antenatal maternal screening tests in Senegal.
AB  - Background: Evidence exists that selective antenatal maternal screening tests
      contribute to the reduction of maternal morbidity and mortality. However, data
      are lacking on coverage with the complete set of recommended tests. The study
      aimed to identify barriers to uptake of the complete set of tests recommended by
      the Ministry of Health in Senegal. Methods: Data were collected in communities,
      antenatal care (ANC) clinics and the laboratories of 11 public health care
      facilities across Senegal. Mixed-methods included ethnography (observations and
      informal conversations), in-depth interviews and workshops at the health
      facilities; structured interviews with 283 women receiving antenatal tests
      ("women in the lab"); in-depth interviews with 81 women in communities who were
      pregnant or had recently delivered ("community women"). Results: Only 13% of
      community women and 22% of women in the lab had received the complete set of
      tests. For various social, financial and antenatal care-related reasons 38% of
      community women who visited antenatal care facilities did not access a
      laboratory. The lowest test uptake was in women receiving antenatal care at
      health posts. Barriers at the laboratory level were the cost of the test, stock
      outs of reagents, and broken equipment. Midwives were the main gatekeepers of the
      laboratory, not requesting (all) tests because of assumptions about women's
      financial problems and reliance on clinical symptoms. Conclusion: In Senegal,
      recommended antenatal maternal screening tests are substantially underutilized.
      Efforts to increase test uptake should include accessible testing guidelines,
      reducing the cost of tests, raising awareness about the reasons for tests, and
      making the complete test set in point-of-care format accessible in peripheral
      health posts. National and international antenatal care policies and programs
      should facilitate access to maternal screening tests as a contribution to
      reducing maternal and infant morbidity and mortality.

PMID- 29349191
TI  - Trends in psychological distress and alcoholism after The Great East Japan
      Earthquake of 2011.
AB  - Aims: Many studies have shown that natural disasters affect mental health;
      however, longitudinal data on post-disaster mental health problems are scarce.
      The aims of our study were to investigate the trend in psychological distress and
      alcoholism after The Great East Japan Earthquake and tsunami in north eastern
      Japan, in March 2011. Methods: A longitudinal study was conducted using annual
      health check data for the general population, in the city of Higashi-Matsushima,
      which was affected by the high impact of tsunami. In 2012 and 2013, the Kessler
      Psychological Distress Scale and the CAGE questionnaire (for screening for
      alcoholism) were used to assess psychological distress and prevalence of
      alcoholism. Results: Of 11,855 total eligible residents, 2192 received the annual
      check in 2012 and 2013. The prevalence of mental illness and the mean score of
      alcoholism tendency increased during the follow-up period. The majority of
      respondents (43.8%) with baseline serious mental illness (SMI) continued to have
      SMI at follow-up; only 16.7% reported recovering. Older age, female sex, and
      severity of home damage predicted higher psychological distress, while male sex
      was a risk factor for alcoholism at follow-up. Conclusions: Psychological
      distress deteriorated 2 years after the huge natural disaster, compared with 1
      year after the disaster. Long-term mental health care is needed for those
      affected by natural disasters, particularly those who have suffered loss.

PMID- 29349192
TI  - Changing medical relationships after the ACA: Transforming perspectives for
      population health.
AB  - American health care has undergone significant organizational change in recent
      decades. But what is the state of core medical relationships in the wake of these
      changes? Throughout ACA-era health care reform, the doctor-patient relationship
      was targeted as a particularly important focus for improving communication and
      health outcomes. Recent developments however have shifted the focus from
      individual-level outcomes to the wellbeing of populations. This, we argue,
      requires a fundamental rethinking of health care reform as an opportunity to
      renegotiate relationships. For example, the move to population medicine requires
      that the very concept of a patient be resituated and the scope of relevant
      relationships expanded. Medical relationships in this era of health care are
      likely to include partnerships between various types of clinicians and the
      communities in which patients reside, as well as a host of new actors, from
      social workers and navigators to scribes and community health workers. To address
      the upstream determinants of population health, providers must be increasingly
      willing and trained to collaborate with community stakeholders to address both
      medical and non-medical issues. These community-based partnerships are critical
      to providing health care that is both relevant and appropriate for addressing
      problems, and sustainable. Approaching health care reform, and the focus on
      population health, as a fundamental reworking of relationships provides scholars
      with a sharper theoretical lens for understanding 21st century American health
      care.

PMID- 29349193
TI  - An analysis of weight perception and physical activity and dietary behaviours
      among youth in the COMPASS study.
AB  - Purpose: Weight misperceptions appear common among youth, potentially influencing
      their motivation to engage in health-related behaviours; however, the direction
      of impact remains unclear. The current study examined how weight perception
      influences physical activity (PA) and diet among youth. Methods: This study used
      2-year linked data of 19,322 grade 9-12 students from Year 2 (Y2:2013-2014) and 3
      (Y3:2014-2015) of the COMPASS study. Generalized Estimating Equation models
      tested the effect of Y3 weight perception on the various Y3 PA and dietary
      behaviour measures, adjusting for Y3 covariates (grade, race/ethnicity, weekly
      spending money), school cluster, school area median household income, and the Y2
      outcome. Models were stratified by gender and body mass index (BMI)
      classification. Results: Regardless of BMI status, overweight perceptions among
      boys and girls were associated with lower likelihoods of playing school sports,
      physical education class enrollment, meeting resistance exercise recommendations,
      eating breakfast regularly, and less vigorous-intensity PA, and among boys only,
      lower odds of meeting PA guidelines, compared to their peers who perceived their
      weight as "about right". In boys with normal-weight BMIs, underweight perceptions
      predicted less vigorous-intensity PA, and lower odds of physical education class
      enrollment, and of meeting PA and resistance exercise recommendations, than
      "about right" perceptions. Among girls, underweight perceptions predicted lower
      likelihoods of engaging in adequate resistance exercise and playing intramurals,
      and greater odds of eating fast food on weekends, purchasing snacks, and drinking
      energy drinks and sugar-sweetened beverages. Girls with overweight/obese BMIs who
      perceived their weight as such were less likely to consume adequate fruits and
      vegetables relative to their counterparts with "about right" weight perceptions.
      Conclusions: Overall, weight perceptions of "about right" appear more favourable
      for health behaviours among youth across the weight range. Results suggest
      obesity prevention strategies aiming to increase awareness of weight status may
      have unintended effects.

PMID- 29349194
TI  - The interplay of race, socioeconomic status and neighborhood residence upon birth
      outcomes in a high black infant mortality community.
AB  - This study examined the interrelationship of race and socioeconomic status (SES)
      upon infant birthweight at the individual and neighborhood levels within a
      Midwestern US county marked by high Black infant mortality. The study conducted a
      multi-level analysis utilizing individual birth records and census tract datasets
      from 2010, linked through a spatial join with ArcGIS 10.0. The maternal
      population of 2861 Black and White women delivering infants in 2010, residing in
      57 census tracts within the county, constituted the study samples. The main
      outcome was infant birthweight. The predictors, race and SES were dichotomized
      into Black and White, low-SES and higher-SES, at both the individual and census
      tract levels. A two-part Bayesian model demonstrated that individual-level race
      and SES were more influential birthweight predictors than community-level
      factors. Specifically, Black women had 1.6 higher odds of delivering a low
      birthweight (LBW) infant than White women, and low-SES women had 1.7 higher odds
      of delivering a LBW infant than higher-SES women. Moderate support was found for
      a three-way interaction between individual-level race, SES and community-level
      race, such that Black women achieved equity with White women (4.0% Black LBW and
      4.1% White LBW) when they each had higher-SES and lived in a racially congruous
      neighborhood (e.g., Black women lived in disproportionately Black neighborhood
      and White women lived in disproportionately White neighborhood). In sharp
      contrast, Black women with higher-SES who lived in a racially incongruous
      neighborhood (e.g., disproportionately White) had the worst outcomes (14.5% LBW).
      Demonstrating the layered influence of personal and community circumstances upon
      health, in a community with substantial racial disparities, personal race and SES
      independently contribute to birth outcomes, while environmental context,
      specifically neighborhood racial congruity, is associated with mitigated health
      risk.

PMID- 29349195
TI  - Inter-individual inequality in BMI: An analysis of Indonesian Family Life Surveys
      (1993-2007).
AB  - Widening inequalities in mean Body Mass Index (BMI) between social and economic
      groups are well documented. However, whether changes in mean BMI are followed by
      changes in dispersion (or variance) and whether these inequalities are also
      occurring within social groups or across individuals remain understudied. In
      addition, a substantial body of literature exists on the global increase in mean
      BMI and prevalence of overweight and obesity. However, whether this weight gain
      is shared proportionately across the whole spectrum of BMI distribution, also
      remains understudied. We examined changes in the distribution of BMI at the
      population level over time to understand how changes in the dispersion reflect
      between-group compared to within-group inequalities in weight gain. Moreover, we
      investigated the entire distribution of BMI to determine in which percentiles the
      most weight gain is occurring over time. Utilizing four waves (from 1993 to 2007)
      of Indonesian Family Life Surveys (IFLS), we estimated changes in the mean and
      the variance of BMI over time and across various socioeconomic groups based on
      education and households' expenditure per capita in 53,648 men and women aged 20
      50 years. An increase in mean and standard deviation was observed among men (by
      4.3% and 25%, respectively) and women (by 7.3% and 20%, respectively) over time.
      Quantile-Quantile plots showed that higher percentiles had greater increases in
      BMI compared to the segment of the population at lower percentiles. While between
      socioeconomic group differences decreased over time, within-group differences
      increased and were more prominent among individuals with poor education and lower
      per capita expenditures. Population changes in BMI cannot be fully described by
      average trends or single parameters such as the mean BMI. Moreover, greater
      increases in within-group dispersion compared with between-group differences
      imply that growing inequalities are not merely driven by these socioeconomic
      factors at the population level.

PMID- 29349196
TI  - The association between anti-immigrant policies and perceived discrimination
      among Latinos in the US: A multilevel analysis.
AB  - Research has found a strong inverse association between discrimination and health
      and well-being. Most of these studies have been conducted among African
      Americans, and have examined the relationship at the individual-level. To fill
      these gaps in knowledge we estimated the prevalence of perceived discrimination
      among a nationally representative sample of Latino adults in the US, and
      investigated the association between state-level anti-immigrant policies and
      perceived discrimination. We merged survey data with a state-level anti-immigrant
      policy index. First, we fit hierarchical logistic regression models to test the
      crude and adjusted association between anti-immigrant policies and perceived
      discrimination. Second, we specified cross-level interaction terms to test
      whether this association differed by relevant individual characteristics. Almost
      70% of respondents reported discrimination (68.4%). More anti-immigrant policies
      were associated with higher levels of discrimination (OR=1.62, 95% CI 1.16, 2.24,
      p=0.01). The association between anti-immigrant policies and discrimination
      differed by place of origin (p=0.001) and was marginally moderated by generation
      status (p=0.124). Anti-immigrant policies stigmatize both foreign and US-born
      Latinos by creating a hostile social environment which affects their experiences
      of discrimination. These non-health policies can adversely affect Latino health,
      in part through exposure to discrimination, and may help explain health patterns
      among Latinos in the US.

PMID- 29349197
TI  - Income disparities in cardiovascular health across the lifespan.
AB  - Using data from the 1999-2014 National Health and Nutrition Examination Survey (n
      ~ 46,000), this study documents income disparities in the age patterning of
      cardiovascular conditions across the lifespan in the U.S. The conditions were
      assessed from laboratory test results, self-reports of medications used to treat
      specific conditions, and anthropometric measurements, allowing us to capture
      whether individuals at given ages had developed the various conditions,
      regardless of previous diagnosis and treatment. We found evidence of large income
      disparities in the presence of cardiovascular conditions and risk factors for
      females, smaller disparities in the same conditions for males, and few
      disparities that increased with age for either gender. Results were very similar
      when considering disparities by education instead of income. The findings suggest
      that the widening socioeconomic gradients in health over the lifespan found in
      many previous studies-which have generally focused on self-rated health, activity
      limitations, or diagnosed conditions-reflect, at least to some extent,
      differences in diagnosis, treatment, and management of health conditions rather
      than age-related differences in developing them. The findings also suggest that
      preventive healthcare is not an important source of socioeconomic disparities in
      cardiovascular health in the U.S., at least for men. The observed patterns of
      income disparities in cardiovascular conditions over the lifespan are more
      consistent with theories of early life conditions and the imprinting of health
      endowments and susceptibilities early in life than with cumulative life exposure
      or stress hypotheses.

PMID- 29349198
TI  - Invited commentary: The long term impact of forced migration during childhood on
      adult health.
AB  - Saarela and Elo (SSM-Population Health; Volume 2, December 2016, Pages 813-823)
      provide new evidence of early life forced displacement not being adversely
      associated with adult health. Their study highlights some of the challenges to
      identifying a causal effect of childhood exposure on adult health in the context
      of complex emergencies. Importantly, it opens up for future research that can
      address commonly recognized sources of bias and identify intervening pathways
      linking forced migration with adult health outcomes.

PMID- 29349199
TI  - Efficiency or equity? Simulating the impact of high-risk and population
      intervention strategies for the prevention of disease.
AB  - Maximizing both efficiency and equity are core considerations for population
      health. These considerations can result in tension in population health science
      as we seek to improve overall population health while achieving equitable health
      distributions within populations. Limited work has explored empirically the
      consequences of different population health intervention strategies on the burden
      of disease and on within- and between-group differences in disease. To address
      this gap, we compared the impact of four simulated interventions using data from
      the National Health and Nutrition Examination Survey. In particular, we focus on
      assessing how population and high-risk primary prevention and population and high
      risk secondary interventions efforts to reduce smoking behavior influence
      systolic blood pressure (SBP) and hypertension, and how such strategies influence
      inequalities in SBP by income. The greatest reductions in SBP mean and standard
      deviation resulted from the population secondary prevention. High-risk primary
      and secondary prevention and population secondary prevention programs all yielded
      substantial reductions in hypertension prevalence. The effect of population
      primary prevention did little to decrease population SBP mean and standard
      deviation, as well as hypertension prevalence. Both high-risk strategies had a
      larger impact in the low-income population, leading to the greatest narrowing the
      income-related gap in disease. The population prevention strategies had a larger
      impact in the high-income population. Population health approaches must consider
      the potential impact on both the whole population and also on those with
      different levels of risk for disease within a population, including those in
      under-represented or under-served groups.

PMID- 29349200
TI  - Changes in living arrangements and mortality among older people in China.
AB  - Living arrangements in later life are dynamic, with changes associated with life
      events such as widowhood or moves into an institution. Previous research has
      found particular changes in living arrangements to be associated with an elevated
      risk of mortality. However, research in this area within the context of China is
      limited, despite China being home to the world's largest population of older
      people. This study investigates the impact of changes in living arrangements on
      older persons' survival using the Chinese Longitudinal Healthy Longevity Survey
      from 2002 to 2011. The original sample was 16,064 in 2002, and this study
      includes 6191 individuals who survived in 2005 and had complete information of
      track record in later waves. Changes in living arrangements are examined between
      2002 and 2005. Cox-proportional hazards models are then used to investigate the
      association between the dynamics of living arrangements and respondents' survival
      status from 2005 to 2011 . Results show that men and women who lived in an
      institution in both 2002 and 2005, or who moved into an institution from living
      with family faced a greater risk of dying compared to those continuing to live
      with family. By contrast, continuing to live with family or alone, or moving
      between living with family and living alone, were not associated with an
      increased mortality risk, although there were some differences by gender. The
      institutional care sector in China is still in its infancy, with provision based
      on ability to pay market fees rather than need associated with age-related
      function impairment. The findings show that living in, or moving into, an
      institution is associated with a high mortality risk therefore requires further
      investigation in the context of a rapidly changing Chinese society.

PMID- 29349201
TI  - Factors affecting the physical and mental health of older adults in China: The
      importance of marital status, child proximity, and gender.
AB  - Evidence is accumulating about the association between strong family ties and the
      emotional and physical welfare of older adults, and researchers have identified
      negative consequences of being unmarried, being childless, and/or living alone.
      These associations have been recognized in multiple contexts, including in Asia
      where living with a spouse and/or grown children has been shown in some studies
      to improve elderly well-being. Social support, especially family support, is
      expected to continue to be important where populations are aging and social
      safety nets are weak. Using longitudinal data from the 2010 and 2012 waves of the
      China Family Panel Studies, we focus on the effects of marital status at times 1
      and 2, changes in marital status between the two surveys, and other family
      related indicators of social connectedness on ratings of depression, levels of
      life satisfaction, and self-reported physical health among those aged 50 and
      over. Our sample includes 9831 respondents who have valid data on wellbeing
      indicators for Wave 1 and Wave 2, as well as complete information on the other
      covariates controlled in our analysis. In analyses of the full sample, those who
      were married at both points in time reported lower depression scores than those
      who were never-married, divorced, or widowed at both time points, and those whose
      unions dissolved in the interval. Those who were married at both times also
      generally reported greater levels of life satisfaction than those who were never
      married at both time points and those who became divorced during the interval.
      Important underlying gender differences are observed both for life satisfaction
      and depression. In addition, those who were married at both time points reported
      being in better physical health than those who became widowed during the interval
      (significant primarily for women), and those who had never been married
      (significant primarily for men). Our study contributes to the literature on
      social ties and the wellbeing by highlighting the importance of marital status
      and changing marital status, net of child co-residence and proximity, in China.

PMID- 29349202
TI  - Healthcare access: A sequence-sensitive approach.
AB  - It is widely accepted that healthcare-seeking behaviour is neither limited to nor
      terminated by access to one single healthcare provider. Yet the sequential
      conceptualisation of healthcare-seeking processes has not diffused into
      quantitative research, which continues to analyse healthcare access as a "one
      off" event. The ensuing lack of understanding healthcare behaviour is problematic
      in light of the immense burden of premature death especially in low- and middle
      income countries. This paper presents an alternative approach. Based on a novel
      survey instrument, we analyse original survey data from rural India and China
      that contain 119 unique healthcare pathways among 637 respondents. We offer three
      applications of how such sequential data can be analysed to enhance our
      understanding of people's health behaviour. First, descriptive analysis of
      sequential data enables more a comprehensive representation of people's health
      behaviours, for example the time spent in various healthcare activities, common
      healthcare pathways across different groups, or shifts in healthcare provider
      access during a typical illness. Second, by analysing the effect of mobile
      technology on healthcare-seeking process characteristics, we demonstrate that
      conventional, sequence-insensitive indicators are potentially inconsistent and
      misleading approximations when compared to a more precise, sequence-sensitive
      measure. Third, we describe how sequential data enable transparent and flexible
      evaluations of people's healthcare behaviour. The example of a sequence
      insensitive evaluation suggests that household wealth has no statistical link to
      an illustrative "ideal" form of public healthcare utilisation. In contrast,
      sequence-sensitive evaluations demonstrate that household wealth is associated
      with an increased likelihood of bypassing referral processes and approaching
      unregulated and costly informal and private practitioners before accessing a
      public clinic. Sequential data therefore do not only reveal otherwise neglected
      locational idiosyncrasies, but they also yield deeper insights into the drivers
      of people's health behaviours compared to a conventional approach to "access to
      healthcare."

PMID- 29349204
TI  - Validity of a scale of neighbourhood informal social control relevant to pre
      schoolers' physical activity: A cross-sectional study.
AB  - Childhood physical activity (PA) is important for health across the lifespan.
      Time pre-schoolers spend outdoors, which has been associated with more PA, is
      likely influenced by parents' perception of neighbourhood informal social control
      relevant to pre-schoolers' PA, defined as the willingness of neighbours to
      intervene to ensure social order and a safe community environment for young
      children's active play. To advance measurement of this construct, we assessed
      factorial and construct validities of the PA-related neighbourhood informal
      social control scale for parents of pre-schoolers (PANISC-PP). In 2013-2014, Hong
      Kong primary caregivers (n=394) of 3-5 year-old children completed a socio
      demographic questionnaire, the preliminary version of the PANISC-PP, and self
      report measures of theoretical neighbourhood correlates of PA-related
      neighbourhood informal social control (perceived signs of physical and social
      disorder, community cohesion, perceived stranger danger, risk of unintentional
      injury and traffic safety). The fit of the data to an a priori measurement model
      of the PANISC-PP was examined using confirmatory factor analyses. As the a priori
      model showed inadequate fit to the data, the factor structure was re-specified
      based on theoretical considerations. The final measurement models of the PANISC
      PP showed acceptable fit to the data and consisted of three correlated latent
      factors: "General informal supervision", "Civic engagement for the creation of a
      better neighbourhood environment" and "Educating and assisting neighbourhood
      children". The internal reliability of the subscales was good (Cronbach's alpha
      values 0.82-0.89). Generalised additive mixed models indicated that all subscales
      were positively associated with community cohesion and scores on the subscale
      "Educating and assisting neighbourhood children" were related in the expected
      direction to all indicators of traffic and personal safety, supporting construct
      validity of the PANISC-PP. This study suggests that the PANISC-PP is a reliable
      and valid instrument for assessing parents' perceived neighbourhood informal
      social control related to pre-schoolers' PA.

PMID- 29349203
TI  - Neighbourhood socioeconomic status indices and early childhood development.
AB  - The developmental health of young children is highly influenced by the
      socioeconomic conditions in which they are raised. How to accurately measure
      these conditions is a point of debate in the current literature on child
      development, health, and social determinants. We have evaluated four existing
      indices of socioeconomic status (SES) to determine the most relevant for the
      analysis of early childhood development (ECD) in Canada. Following a literature
      review of published SES indices which used 2006 Canadian Census data, four
      indices were chosen based on their relevance to ECD and the number of citations
      in subsequent articles. These were: the Canadian Deprivation Index, the
      Socioeconomic Factor Index, the Canadian Marginalization Index and an index
      created by the Early Childhood Mapping Project in Alberta, Canada. The indices
      were replicated using SES data for 2038 customized geographic neighbourhoods
      encompassing 99.9% of the Canadian population, and the relationship of the
      indices to ECD was investigated by linking to aggregated data from the Early
      Development Instrument (EDI), a teacher-completed questionnaire used to assess
      kindergarten children's physical, social, emotional, and cognitive development,
      and communication skills. The derived SES indices were compared based on four
      criteria: the input variables used, the index structure, the interpretability of
      the index and the variance they explained (R2) in the different EDI outcome
      measures. In terms of variance explained, material components of the SES indices
      (e.g., income, education) consistently showed the strongest association with
      children's language and cognitive development. The patterns of association for
      the non-material SES components and the other developmental domains of the EDI
      were more complex. We discuss the findings in regard to current developments in
      the field, and the need for refining empirical and theoretical approaches to
      examine associations between different facets of SES contextual factors and
      different aspects of ECD outcomes.

PMID- 29349205
TI  - Cool? Young people investigate living in cold housing and fuel poverty. A mixed
      methods action research study.
AB  - Background: Living in cold housing conditions and risk of fuel poverty presents a
      range of physiological and psychosocial health risks. Limited research has
      specifically investigated the effects of fuel poverty on children and young
      people, and even less has been conducted with youth input into the research
      process. Methods: The Cool? Study used mixed methods, participatory action
      research carried out with youth researchers involved at all stages through
      questionnaire design, analysis, qualitative design, e-interviewing and
      dissemination of results. This article reports on results of an online survey of
      656 adolescents aged 14-16 years completed at 17 schools in New Zealand. Sampling
      was based on selecting schools for invitation, with the probability of selection
      weighted proportional to school size, within strata defined by climate zone.
      Results from a small e-mail interview study of survey respondents who consented
      to follow-up are also reported. Results: The study found that almost half of the
      survey respondents (47%) felt their home was sometimes cold during the winter; a
      further 40% felt their home was often or always cold. More than two thirds of
      respondents (70%) had shivered inside at least once during winter. Respondents
      were more likely to report key indicators of fuel poverty depending on their self
      reported ethnicity, with Maori at increased risk. Living in private rental
      housing or state-owned housing also increased risk of fuel poverty compared to
      those in owner-occupied dwellings. Participants of email interviews expressed
      concern about the widespread problem of cold housing for youth and a desire for
      Government intervention. Conclusion: The integrated results confirm that cold
      housing and risk of fuel poverty are important problems for young people in New
      Zealand. Results contribute to the evidence-base for policy targeting of schemes
      such as the Government-sponsored retrofitting of insulation to households with
      dependent children.

PMID- 29349206
TI  - Dark shadow of the long white cloud: Neighborhood safety is associated with self
      rated health and cortisol during pregnancy in Auckland, Aotearoa/New Zealand.
AB  - Auckland, Aotearoa/New Zealand is a culturally and ethnically diverse city.
      Despite popular global conceptions regarding its utopian nature, the lived
      experience for many individuals in Auckland attests to the substantial social,
      economic, and health inequalities that exist there. In particular, rapidly rising
      home prices constrain housing decisions and force individuals to live in less
      desirable neighborhoods, with potential impacts on individual health. One of the
      pathways through which adverse neighborhood conditions could impact health is
      through alterations in the functioning of the hypothalamic pituitary adrenal
      (HPA)-axis, which regulates the physiological stress response. This paper
      evaluates the relationship between perceived neighborhood safety, self-rated
      health, and cortisol, an end product of HPA-axis activation, among women in late
      pregnancy. Pregnant women living in neighborhoods where they were concerned about
      safety of their property had poorer self-rated health and elevated morning
      cortisol, even after adjusting for maternal age, material deprivation, and
      ethnicity. However, fear of personal safety was unrelated to self-rated health
      and cortisol. These results suggest that maternal health in pregnancy is
      sensitive to perceptions regarding neighborhood safety. Such findings are
      important since higher cortisol levels in pregnancy could not only influence
      maternal health, but also the health and development of women's children.

PMID- 29349207
TI  - Gender career divide and women's disadvantage in depressive symptoms and physical
      limitations in France.
AB  - This study investigated the relationship between women's disadvantage in mental
      health and physical functioning and gender differences in career backgrounds.
      Sexual division of labor persists and key career characteristics are
      overrepresented in women: low-skilled first job, downward occupational
      trajectory, interruptions. These interrelated characteristics are usually linked
      to poor health. Their overrepresentation in women may be related to the female
      male health gap; however, it may not if overrepresentation transposed into
      substantially weaker associations with poor health outcomes. To address this
      question, we used the French population survey "Health and Occupational
      Trajectories" (2006) and focused on 45-74 year-old individuals who ever worked
      (n=7537). Past career characteristics were qualified by retrospective
      information. Logistic regressions identified past characteristics related to
      current depressive symptoms and physical limitations. Non-linear decomposition
      showed whether these characteristics contributed to the gender health gap,
      through their different distribution and/or association with health. The
      overrepresentation of unskilled first jobs, current and past inactivity and
      unemployment in women contributed to their excess depressive symptoms. These
      contributions were only slightly reduced by the weaker mental health-relatedness
      of current inactivity in women and increased by the stronger relatedness of low
      skilled and self-employed first jobs. Overrepresentation of current inactivity,
      past interruptions and downward trajectories also contributed positively to
      women's excess physical limitations. Gender-specific career backgrounds were
      significantly linked to women's disadvantage in mental health and physical
      functioning. We need to further explore whether equalization of opportunities,
      especially at the early stages and in terms of career continuity, could help to
      reduce women's mental and physical health disadvantage.

PMID- 29349208
TI  - In sickness and in health: The role of marital partners in cancer survival.
AB  - Married cancer patients enjoy a survival advantage, potentially attributable to
      better health at diagnosis, earlier contact with health personnel, and/or access
      to resources to ensure more optimal treatment. These mechanisms only invoke the
      mere presence of a partner, but partners bring varying amounts of resources into
      the household. It is likely that also spousal resources contribute to
      differentials in survival net of own resources, as gradients in survival by the
      latter are well documented. Our aim is to examine the combined roles of own and
      spouses' socioeconomic characteristics (SES) and age for cancer survival. Almost
      268,000 married patients diagnosed with a first cancer after age 50 during 1975
      2007 were identified from the Norwegian Cancer Registry and other national
      registers. In a sequence of hazard models, differences in survival by patients'
      own education, income and age and the role of spouses' characteristics were
      assessed. Furthermore, we also assessed the importance of homogamy/heterogamy
      along the same dimensions. Partners' characteristics clearly matter for survival.
      The relative survival of patients with highly educated partners, net of their own
      education, is significantly higher than that of patients with lesser-educated
      partners. Somewhat similar effects are observed for income, net of education. A
      less consistent pattern is observed for age, although non-normative heterogamy
      patterns in age and income appear to be associated with a survival disadvantage.
      The naive perspective of only considering the presence of partners may thus
      conceal important differences in cancer survival. Health personnel may take
      advantage of such knowledge in interactions with patients and their families, and
      gather information on resources in immediate networks that may impact prognosis
      favorable and/or unfavorable and help patients utilize these resources to improve
      prognosis.

PMID- 29349209
TI  - Immigration concern and the white/non-white difference in smoking: Group position
      theory and health.
AB  - National data indicate that U.S. whites have a higher prevalence of smoking
      compared to non-whites. Group position theory and public opinion data suggest
      racial differences in immigration concern. This study examines whether
      immigration concern mediates the racial difference in smoking. Drawing on the
      2012 General Social Survey, the 2012 American National Election Study, and the
      2006 Portraits of American Life Study, immigration concern was associated with
      smoking, controlling for covariates across all three nationally representative
      surveys. Mediation analysis indicated that immigration concern partially mediated
      the higher odds of smoking among whites across all surveys. Immigration concern
      also presents a possible explanation for the healthy immigrant advantage and
      Hispanic paradox as they pertain to smoking differences.

PMID- 29349210
TI  - Early-life conditions and child development: Evidence from a violent conflict.
AB  - This paper investigates how the exposure to violent conflicts in utero and in
      early and late childhood affect human capital formation. I focus on a wide range
      of child development outcomes, including novel cognitive and non-cognitive
      indicators. Using monthly and municipality-level variation in the timing and
      severity of massacres in Colombia from 1999 to 2007, I show that children exposed
      to terrorist attacks in utero and in childhood achieve lower height-for-age (0.09
      SD) and cognitive outcomes (PPVT falls by 0.18SD and math reasoning and general
      knowledge fall by 0.16SD), and that these results are robust to controlling for
      mother fixed-effects. The timing of these exposures matters and differs by type
      of skill. In terms of parental investments, I find some evidence that parents
      reinforce the negative effects of violence by increasing their frequency of
      physical aggression.

PMID- 29349211
TI  - Who votes for public health? U.S. senator characteristics associated with voting
      in concordance with public health policy recommendations (1998-2013).
AB  - Background: The voting behaviors of elected officials shape the public's health.
      Little is known, however, about the characteristics of elected officials who vote
      in concordance with public health policy recommendations. This article presents
      the results of study conducted with the aims of: 1) testing the hypothesis that
      US Democrat Senators vote in concordance with American Public Health Association
      (APHA) policy recommendations more frequently than US Republican Senators, 2)
      identifying US Senator characteristics independently associated with voting in
      concordance with APHA, and 3) assessing trends in APHA voting concordance by
      political party. Methods: We created a legislative dataset of 1434 votes cast on
      111 legislative proposals by 184 US Senators during the years 1998 through 2013.
      Mixed effects linear regression models were used to estimate the independent
      contributions of political party, gender, geographic region, and year effects to
      annual APHA voting concordance. Votes were nested within Senators who were nested
      within States to account for non-independence and models considered potential for
      time and spatial patterns in the data. Results: Adjusting for covariates and
      accounting for serial and spatial autocorrelation, Democrats averaged 59.1
      percentage points higher in annual APHA voting concordance than Republicans (95%
      CI: 55.5, 62.7), females averaged 7.1 percentage points higher than males (95%
      CI: 1.9, 12.3), and Northeastern Senators averaged 16.1 percentage points higher
      than Southern Senators (95% CI: 9.1, 23.1). Conclusions: Elected official's
      political party affiliation, gender, and geographic region are independently
      associated with public health voting decisions and should be considered when
      targeting and tailoring science-based policy dissemination strategies.

PMID- 29349212
TI  - Place, health, and community attachment: Is community capacity associated with
      self-rated health at the individual level?
AB  - Community-level interventions dominate contemporary public health responses to
      health inequalities as a lack of political will has discouraged action at a
      structural level. Health promoters commonly leverage community capacity to
      achieve programme goals, yet the health implications of low community capacity
      are unknown. In this study, we analyse perceptions of community capacity at the
      individual-level to explore how place-based understandings of identity and
      connectedness are associated with self-rated health. We examine associations
      between individual community capacity, self-rated health and income using a cross
      sectional survey that was disseminated to 303 residents of four small
      (populations 1500-2000) New Zealand towns. Evidence indicating a relationship
      between individual community capacity and self-reported health was unconvincing
      once the effects of income were incorporated. That is, people who rated their
      community's capacity higher did not have better self-rated health. Much stronger
      evidence supported the relationship between income and both higher individual
      community capacity and higher self-rated health. We conclude that individual
      community capacity may mediate the positive association between income and
      health, however, overall we find no evidence suggesting that intervening to
      enhance individual community capacity is likely to improve health outcomes.

PMID- 29349213
TI  - Socioeconomic inequality in morbid obesity with body mass index more than 40
      kg/m2 in the United States and England.
AB  - Introduction: This study evaluated socioeconomic inequality in morbid obesity
      (body mass index, BMI >=40 kg/m2) through an analysis of population health survey
      data in the United States (US) and England (UK). Methods: We analysed data for
      the National Health and Nutrition Examination Survey and the Health Survey for
      England for 2011 to 2014. Age-adjusted odds ratios (AOR) were used to evaluate
      income- and education-inequality. Results: There were 26,898 eligible UK and
      10,628 US participants. Morbid obesity was more frequent in women than men, and
      higher in the US than the UK (men: US, 4.8%; UK, 1.7%; women US, 9.6%; UK, 3.7%).
      In the UK, morbid obesity showed graded income-inequality in both genders (AOR,
      for lowest income quintile: men, 1.83, 95% confidence interval 1.16 to 2.88;
      women, 2.18, 1.55 to 3.07), as well as education-inequality (AOR for no school
      qualifications, men 2.57, 1.64 to 4.02; women, 2.18, 1.55 to 3.07). In the US,
      morbid obesity showed a consistent gradient only for income in women (AOR for
      lowest income quintile 1.97, 1.19 to 3.25). When compared with all other US
      groups, having college education (AOR, men, 0.56, 0.29 to 1.08; women, 0.36, 0.22
      to 0.60) or household income >=$75 000 (AOR, men 0.52, 0.27 to 0.98; women, 0.51,
      0.33 to 0.80) appeared to protect against morbid obesity. Conclusions: Morbid
      obesity is associated with lower socioeconomic status in men and women in the UK.
      In the US, morbid obesity was twice as prevalent, but less strongly associated
      with socioeconomic status, suggesting that morbid obesity may now have spread to
      all but the highest socioeconomic groups.

PMID- 29349214
TI  - Performance-based financing to increase utilization of maternal health services:
      Evidence from Burkina Faso.
AB  - Performance-based financing (PBF) programs are increasingly implemented in low
      and middle-income countries to improve health service quality and utilization. In
      April 2011, a PBF pilot program was launched in Boulsa, Leo and Titao districts
      in Burkina Faso with the objective of increasing the provision and quality of
      maternal health services. We evaluate the impact of this program using facility
      level administrative data from the national health management information system
      (HMIS). Primary outcomes were the number of antenatal care visits, the proportion
      of antenatal care visits that occurred during the first trimester of pregnancy,
      the number of institutional deliveries and the number of postnatal care visits.
      To assess program impact we use a difference-in-differences approach, comparing
      changes in health service provision post-introduction with changes in matched
      comparison areas. All models were estimated using ordinary least squares (OLS)
      regression models with standard errors clustered at the facility level. On
      average, PBF facilities had 2.3 more antenatal care visits (95% CI [0.446
      4.225]), 2.1 more deliveries (95% CI [0.034-4.069]) and 9.5 more postnatal care
      visits (95% CI [6.099, 12.903]) each month after the introduction of PBF.
      Compared to the service provision levels prior to the interventions, this implies
      a relative increase of 27.7 percent for ANC, of 9.2 percent for deliveries, and
      of 118.7 percent for postnatal care. Given the positive results observed during
      the pre-pilot period and the limited resources available in the health sector,
      the PBF program in Burkina Faso may be a low-cost, high impact intervention to
      improve maternal and child health.

PMID- 29349215
TI  - Public health and the economy could be served by reallocating medical
      expenditures to social programs.
AB  - As much as 30% of US health care spending in the United States does not improve
      individual or population health. To a large extent this excess spending results
      from prices that are too high and from administrative waste. In the public
      sector, and particularly at the state level, where budget constraints are severe
      and reluctance to raise taxes high, this spending crowds out social, educational,
      and public-health investments. Over time, as spending on medical care increases,
      spending on improvements to the social determinants of health are starved. In
      California the fraction of General Fund expenditures spent on public health and
      social programs fell from 34.8% in fiscal year 1990 to 21.4% in fiscal year 2014,
      while health care increased from 14.1% to 21.3%. In spending more on healthcare
      and less on other efforts to improve health and health determinants, the state is
      missing important opportunities for health-promoting interventions with a strong
      financial return. Reallocating ineffective medical expenditures to proven and
      cost-effective public health and social programs would not be easy, but
      recognizing its potential for improving the public's health while saving
      taxpayers billions of dollars might provide political cover to those willing to
      engage in genuine reform. National estimates of the percent of medical spending
      that does not improve health suggest that approximately $5 billion of
      California's public budget for medical spending has no positive effect on health.
      Up to 10,500 premature deaths could be prevented annually by reallocating this
      portion of medical spending to public health. Alternatively, the same expenditure
      could help an additional 418,000 high school students to graduate.

PMID- 29349216
TI  - Family of origin and educational inequalities in mortality: Results from 1.7
      million Swedish siblings.
AB  - Circumstances in the family of origin have short- and long-term consequences for
      people's health. Family background also influences educational achievements -
      achievements that are clearly linked to various health outcomes. Utilizing
      population register data, we compared Swedish siblings with different levels of
      education (1,732,119 individuals within 662,095 sibships) born between 1934 and
      1959 and followed their death records until the end of 2012 (167,932 deaths). The
      educational gradient in all-cause mortality was lower within sibships than in the
      population as a whole, an attenuation that was strongest at younger ages (< 50
      years of age) and for those with a working class or farmer background. There was
      substantial variation across different causes of death with clear reductions in
      educational inequalities in, e.g., lung cancer and diabetes, when introducing
      shared family factors, which may indicate that part of the association can be
      ascribed to circumstances that siblings have in common. In contrast, educational
      inequalities in suicide and, for women, other mental disorders increased when
      adjusting for factors shared by siblings. The vast variation in the role of
      childhood conditions for the education-mortality association may help us to
      further understand the interplay between family background, education, and
      mortality. The increase in the education gradient in suicide when siblings are
      compared may point towards individually oriented explanations ('non-shared
      environment'), perhaps particularly in mental disorders, while shared family
      factors primarily seem to play a more important role in diseases in which health
      behaviors are most significant.

PMID- 29349217
TI  - The Mothers on Respect (MOR) index: measuring quality, safety, and human rights
      in childbirth.
AB  - Background: Abuse of human rights in childbirth are documented in low, middle and
      high resource countries. A systematic review across 34 countries by the WHO
      Research Group on the Treatment of Women During Childbirth concluded that there
      is no consensus at a global level on how disrespectful maternity care is
      measured. In British Columbia, a community-led participatory action research team
      developed a survey tool that assesses women's experiences with maternity care,
      including disrespect and discrimination. Methods: A cross-sectional survey was
      completed by women of childbearing age from diverse communities across British
      Columbia. Several items (31/130) assessed characteristics of their communication
      with care providers. We assessed the psychometric properties of two versions of a
      scale (7 and 14 items), among women who described experiences with a single
      maternity provider (n=2514 experiences among 1672 women). We also calculated the
      proportion and selected characteristics of women who scored in the bottom 10th
      percentile (those who experienced the least respectful care). Results: To
      demonstrate replicability, we report psychometric results separately for three
      samples of women (S1 and S2) (n=2271), (S3, n=1613). Analysis of item-to-total
      correlations and factor loadings indicated a single construct 14-item scale,
      which we named the Mothers on Respect index (MORi). Items in MORi assess the
      nature of respectful patient-provider interactions and their impact on a person's
      sense of comfort, behavior, and perceptions of racism or discrimination. The
      scale exhibited good internal consistency reliability. MORi- scores among these
      samples differed by socio-demographic profile, health status, experience with
      interventions and mode of birth, planned and actual place of birth, and type of
      provider. Conclusion: The MOR index is a reliable, patient-informed quality and
      safety indicator that can be applied across jurisdictions to assess the nature of
      provider-patient relationships, and access to person-centered maternity care.

PMID- 29349218
TI  - Comparing methods of targeting obesity interventions in populations: An agent
      based simulation.
AB  - Social networks as well as neighborhood environments have been shown to effect
      obesity-related behaviors including energy intake and physical activity.
      Accordingly, harnessing social networks to improve targeting of obesity
      interventions may be promising to the extent this leads to social multiplier
      effects and wider diffusion of intervention impact on populations. However, the
      literature evaluating network-based interventions has been inconsistent.
      Computational methods like agent-based models (ABM) provide researchers with
      tools to experiment in a simulated environment. We develop an ABM to compare
      conventional targeting methods (random selection, based on individual obesity
      risk, and vulnerable areas) with network-based targeting methods. We adapt a
      previously published and validated model of network diffusion of obesity-related
      behavior. We then build social networks among agents using a more realistic
      approach. We calibrate our model first against national-level data. Our results
      show that network-based targeting may lead to greater population impact. We also
      present a new targeting method that outperforms other methods in terms of
      intervention effectiveness at the population level.

PMID- 29349219
TI  - Drug involvement in fatal overdoses.
AB  - Death certificate data from the Multiple Cause of Death (MCOD) files were
      analyzed to better understand the drug categories most responsible for the
      increase in fatal overdoses occurring between 1999 and 2014. Statistical
      adjustment methods were used to account for the understatement in reported drug
      involvement occurring because death certificates frequently do not specify which
      drugs were involved in the deaths. The frequency of combination drug use
      introduced additional uncertainty and so a distinction was made between any
      versus exclusive drug involvement. Many results were sensitive to the starting
      and ending years chosen for examination. Opioid analgesics played a major role in
      the increased drug deaths for analysis windows starting in 1999 but other drugs,
      particularly heroin, became more significant for recent time periods. Combination
      drug use was important for all time periods and needs to be accounted for when
      designing policies to slow or reverse the increase in overdose deaths.

PMID- 29349220
TI  - Adult mortality in sub-saharan Africa, Zambia: Where do adults die?
AB  - Place of death remains an issue of growing interest and debate among scholars as
      an indicator of quality of end-of-life care in developed countries. In sub
      Saharan Africa, however, variations in place of death may suggest inequalities in
      access to and the utilization of health care services that should be addressed by
      public health interventions. Limited research exists on factors associated with
      place of death in sub-Saharan Africa. The study examines factors associated with
      the place of death among Zambian adults aged 15-59 years using the 2010-2012
      sample vital registration with verbal autopsy survey (SAVVY) data, descriptive
      statistics and multivariate logistic regression analysis. Results show that more
      than half of the adult deaths occurred in a health facility and two-fifths died
      at home. Higher educational attainment, urban versus rural residence, and being
      of female gender were significant predictors of the place of death. Improvement
      in educational attainment and investment in rural health facilities and the
      health care system as a whole may improve access and utilization of health
      services among adults.

PMID- 29349221
TI  - Women at war: The crucible of Vietnam.
AB  - Relatively little has been written about the military women who served in
      Vietnam, and there is virtually no literature on deployed civilian women (non
      military). We examined the experiences of 1285 American women, military and
      civilian, who served in Vietnam during the war and responded to a mail survey
      conducted approximately 25 years later in which they were asked to report and
      reflect upon their experiences and social and health histories. We compare
      civilian women, primarily American Red Cross workers, to military women
      stratified by length of service, describe their demographic characteristics and
      warzone experiences (including working conditions, exposure to casualties and
      sexual harassment), and their homecoming following Vietnam. We assess current
      health and well-being and also compare the sample to age- and temporally
      comparable women in the General Social Survey (GSS), with which our survey shared
      some measures. Short-term (<10 years) military service women (28%) were more
      likely to report their Vietnam experience as "highly stressful" than were career
      (>20 years; 12%) and civilian women (13%). Additional differences regarding
      warzone experiences, homecoming support, and health outcomes were found among
      groups. All military and civilian women who served in Vietnam were less likely to
      have married or have had children than women from the general population, chi2
      (8) = 643.72, p < .001. Career military women were happier than women in the
      general population (48% were "very happy", as compared to 38%). Civilian women
      who served in Vietnam reported better health than women in the other groups.
      Regression analyses indicated that long-term physical health was mainly
      influenced by demographic characteristics, and that mental health and PTSD
      symptoms were influenced by warzone and homecoming experiences. Overall, this
      paper provides insight into the experiences of the understudied women who served
      in Vietnam, and sheds light on subgroup differences within the sample.

PMID- 29349222
TI  - A comprehensive analysis of the mortality experience of hispanic subgroups in the
      United States: Variation by age, country of origin, and nativity.
AB  - Although those identifying as "Hispanic or Latino" experience lower adult
      mortality than the more socioeconomically advantaged non-Hispanic white
      population, the ethnic category Hispanic conceals variation by country of origin,
      nativity, age, and immigration experience. The current analysis examines adult
      mortality differentials among 12 Hispanic subgroups by region of origin and
      nativity, and non-Hispanic whites, adjusting for socioeconomic and demographic
      characteristics. We use the National Health Interview Survey Linked Mortality
      Files pooled 1990-2009 to obtain sufficient sample of each subgroup to calculate
      mortality estimates by sex and age group (25-64, 65+). Among adults aged 65 and
      over, all foreign born subgroups have an advantage over non-Hispanic whites, and
      many USB subgroups exhibit an advantage in the adjusted model. Foreign-born
      Dominicans, Central/South Americans, and other Hispanics exhibit consistent
      advantages across models for both men and women, aged 25-64 and 65 and over, and
      both unadjusted and adjusted for socioeconomic covariates. Both US-born and
      foreign-born Mexicans between ages 25 and 64 have mortality disadvantaged
      relative to non-Hispanic whites, while older Mexicans exhibit clear advantages.
      Our results complicate the traditional formulation of the Hispanic Paradox and
      cast doubt on the singularity of the mortality experience of those of Hispanic
      origin.

PMID- 29349223
TI  - Social participation and self-rated psychological health: A longitudinal study on
      BHPS.
AB  - Although social capital has been hypothesized to have positive influence on
      psychological health, a relationship between social capital dimensions and
      psychological wellbeing has rarely been found. This longitudinal study
      investigates the relationship between social participation in associations and
      self-rated psychological health. The paper uses five waves of the British
      Household Panel Survey (BHPS) from 1991 to 1995 (unbalanced panel N=45,761).
      Ordered logit fixed effect methods were used to study the longitudinal link
      between structural social capital (being a member, active, and both a member and
      active in associations) and self-rated psychological health assessed by single
      items of the General Health Questionnaire (GHQ-12) controlling for age, marital
      status, household size, number of children, education, income, economic status,
      number of visits to the GP and health problems. The paper shows that being only a
      member and only active in associations has no statistical relationship with
      almost all the items of the GHQ-12. Instead, being both a member and active in
      associations is linked to all "positive" items of self-rated psychological health
      and to two main "negative" items of psychological wellbeing. These findings
      highlight the protective role of being both a member and active in associations
      against poor psychological health outcomes.

PMID- 29349224
TI  - A couple-level analysis of participation in physical activity during
      unemployment.
AB  - There is a well-documented negative correlation between unemployment and health.
      Yet, little research has examined how unemployment relates to participation in
      physical activity, and few researchers have considered how an individual's
      unemployment may affect the health of their spouse or partner. The purpose of
      this study is to answer three questions: 1. Is one's own unemployment associated
      with changes in physical activity participation? 2. Is one's partner's
      unemployment associated with changes in physical activity participation? 3. Do
      changes in physical activity behaviors associated with unemployment differ by
      gender? This study uses nationally representative, longitudinal data on couples
      in the United States, covering the period 1999-2013. These data, obtained from
      the Panel Study of Income Dynamics, are used to estimate fixed-effects models of
      the relationships between one's own, and one's partner's, unemployment and
      participation in physical activity. I find that for men unemployment is not
      associated with changes in physical activity time. For women, own unemployment is
      associated with increases in physical activity, whereas a partner's unemployment
      is associated with decreases in physical activity. I argue that unemployed women,
      unlike men, are able to take advantage of the increased availability of time
      through reduced labor supply to invest in their health during unemployment, which
      could have positive long-run consequences. Results suggest the importance of
      studying unemployment and health at the household level and suggest a need for
      further investigation into gender differences in unemployment and health.

PMID- 29349225
TI  - Intergenerational differences in smoking among West Indian, Haitian, Latin
      American, and African blacks in the United States.
AB  - Due in large part to increased migration from Africa and the Caribbean, black
      immigrants and their descendants are drastically changing the contours of health
      disparities among blacks in the United States. While prior studies have examined
      health variation among black immigrants by region of birth, few have explored the
      degree of variation in health behaviors, particularly smoking patterns, among
      first- and second- generation black immigrants by ancestral heritage. Using data
      from the 1995-2011 waves of the Tobacco Use Supplements of the Current Population
      Survey (TUS-CPS), we examine variation in current smoking status among first-,
      second-, and third/higher- generation black immigrants. Specifically, we
      investigate these differences among all black immigrants and then provide
      separate analyses for individuals with ancestry from the English-speaking
      Caribbean (West Indies), Haiti, Latin America, and Africa-the primary sending
      regions of black immigrants to the United States. We also explore differences in
      smoking behavior by gender. The results show that, relative to third/higher
      generation blacks, first-generation black immigrants are less likely to report
      being current smokers. Within the first-generation, immigrants who migrated after
      age 13 have a lower probability of smoking relative to those who migrated at or
      under age 13. Disparities in smoking prevalence among the first-generation by age
      at migration are largest among black immigrants from Latin America. The results
      also suggest that second-generation immigrants with two foreign-born parents are
      generally less likely to smoke than the third/higher generation. We find no
      statistically significant difference in smoking between second-generation
      immigrants with mixed nativity parents and the third or higher generation. Among
      individuals with West Indian, Haitian, Latin American, and African ancestry, the
      probability of being a current smoker increases with each successive generation.
      The intergenerational increase in smoking, however, is slower among individuals
      with African ancestry. Finally, with few exceptions, our results suggest that
      intergenerational gaps in smoking behavior are larger among women compared to
      men. As additional sources of data for this population become available,
      researchers should investigate which ancestral subgroups are driving the
      favorable smoking patterns for the African origin population.

PMID- 29349226
TI  - Seeking relief: Bankruptcy and health outcomes of adult women.
AB  - This study examined the impact of declaring consumer bankruptcy on the physical
      and mental health of adult women and if outcomes differed depending on whether
      the filer received automatic debt discharge under Chapter 7 compared to a debt
      repayment plan with Chapter 13. Sample data consisted of women from the NLSY79
      cohort who completed the age 40 and 50 health modules as of the most recent wave.
      Results indicated a negative effect of bankruptcy on self-assessed health,
      whereas prior health history explained its negative relationship with depressive
      symptoms. Debt liquidation under Chapter 7 was associated with poor physical
      health relative to those who did not file and with depressive symptoms relative
      to Chapter 13 repayment plan filers. Poor health is an unintended consequence for
      women who seek financial relief through bankruptcy.

PMID- 29349227
TI  - Conceptualizing, measuring and evaluating constructs of the adolescent
      neighbourhood social environment: A systematic review.

PMID- 29349228
TI  - Children's migration and lifestyle-related chronic disease among older parents
      'left behind' in india.
AB  - Lifestyle-related chronic diseases such as cardiovascular diseases and diabetes
      are now the leading causes of death and disability in India. Interestingly, those
      Indian states with the highest prevalence of lifestyle-related chronic disease
      among older adults are also found to have the highest rates of international or
      internal out-migration. This paper investigates the association between having
      migrant (adult) children and older parents' lifestyle-related chronic disease in
      India. Bi-variate and multivariate analysis are conducted using data from a
      representative sample of 9507 adults aged 60 and older in seven Indian states
      from the UNFPA project 'Building Knowledge Base on Ageing in India'. The results
      show that for any of the diagnosed conditions of hypertension, diabetes and heart
      disease, the prevalence among older people with a migrant son is higher than
      among those without. More specifically, the odds ratio of reporting a lifestyle
      related chronic disease is higher among older adults with at least one adult son
      living in another district, State or outside India than those with their children
      living closer. This study contributes empirical evidence to the academic and
      policy debate about the consequences of globalization and urbanization for older
      people's health status generally, and particularly their risk for reporting
      chronic diseases that relate to changes in their lifestyle.

PMID- 29349229
TI  - Does gender inequity increase men's mortality risk in the United States? A
      multilevel analysis of data from the National Longitudinal Mortality Study.
AB  - A number of theoretical approaches suggest that gender inequity may give rise to
      health risks for men. This study undertook a multilevel analysis to ascertain if
      state-level measures of gender inequity are predictors of men's mortality in the
      United States. Data for the analysis were taken primarily from the National
      Longitudinal Mortality Study, which is based on a random sample of the non
      institutionalised population. The full data set included 174,703 individuals
      nested within 50 states and had a six-year follow-up for mortality. Gender
      inequity was measured by nine variables: higher education, reproductive rights,
      abortion provider access, elected office, management, business ownership, labour
      force participation, earnings and relative poverty. Covariates at the individual
      level were age, income, education, race/ethnicity, marital status and employment
      status. Covariates at the state level were income inequality and per capita gross
      domestic product. The results of logistic multilevel modelling showed a number of
      measures of state-level gender inequity were significantly associated with men's
      mortality. In all of these cases greater gender inequity was associated with an
      increased mortality risk. In fully adjusted models for all-age adult men the
      elected office (OR 1.05 95% CI 1.01-1.09), business ownership (OR 1.04 95% CI
      1.01-1.08), earnings (OR 1.04 95% CI 1.01-1.08) and relative poverty (OR 1.07 95%
      CI 1.03-1.10) measures all showed statistically significant effects for each 1
      standard deviation increase in the gender inequity z-score. Similar effects were
      seen for working-age men. In older men (65+ years) only the earnings and relative
      poverty measures were statistically significant. This study provides evidence
      that gender inequity may increase men's health risks. The effect sizes while
      small are large enough across the range of gender inequity identified to have
      important population health implications.

PMID- 29349230
TI  - Education, race/ethnicity, and multimorbidity among adults aged 30-64 in the
      National Health Interview Survey.
AB  - Background: Demographic risk factors for multimorbidity have been identified in
      numerous population-based studies of older adults; however, there is less data on
      younger populations, despite the fact that approximately 24% of US adults age 18+
      have multimorbidity. Understanding multimorbidity earlier in the life course is
      critical because of the increased likelihood of long-term disability and loss of
      productivity associated with chronic disease progression. Objective: To examine
      the associations of education and race/ethnicity with mutimorbidity among adults
      aged 30-64 using cross-sectional data from the 2002-2014 National Health
      Interview Surveys. Design: Multimorbidity was defined as having at least 2 of 9
      self-reported health conditions. Educational attainment was categorized as less
      than high school (HS), completed HS or some college, and bachelor's degree or
      higher. Logistic regression models of multimorbidity controlled for time since
      last doctor's visit, demographic and socioeconomic measures. Results: Compared to
      having a bachelor's degree or higher, completing less than HS (OR=1.58, 95% CI =
      1.50-1.66) or HS/some college (OR=1.32, 95% CI = 1.27-1.37) were both associated
      with increased odds of multimorbidity net of all included covariates. Non
      Hispanic Blacks had greater odds of multimorbidity (OR=1.07, 95% CI = 1.02-1.11)
      compared to Non-Hispanic Whites with comparable characteristics. Conclusions:
      Epidemiologic and demographic research on the burden of multimorbidity among non
      elderly adults is limited, but warrants renewed attention given the potential for
      long-term loss of quality of life, productivity, and well-being for non-elderly
      adults. Reducing multimorbidity through health promotion efforts across the
      socioeconomic spectrum and earlier in the life course will be a requirement to
      age successfully and support overall well-being in the aging US population.

PMID- 29349231
TI  - Improving population health by reducing poverty: New York's Earned Income Tax
      Credit.
AB  - Despite the established relationship between adverse health outcomes and low
      socioeconomic status, researchers rarely test the link between health
      improvements and poverty-alleviating economic policies. New research, however,
      links individual-level health improvements to the Earned Income Tax Credit
      (EITC), a broad-based income support policy. We build on these findings by
      examining whether the EITC has ecological, neighborhood-level health effects. We
      use a difference-in-difference analysis to measure child health outcomes in 90
      low- and middle- income neighborhoods before and after the expansion of New York
      State and New York City's EITC policy between 1997-2010. Our study takes
      advantage of the relatively exogenous source of income variation supplied by the
      EITC-legislative changes to EITC policy parameters. This feature minimizes the
      endogeneity problem in studying the relationship between income and health. Our
      estimates link a 15-percentage-point increase in EITC benefit rates to a 0.45
      percentage-point reduction in the low birthweight rate. We do not observe any
      measurable link between EITC benefits and prenatal health or asthma-related
      pediatric hospitalization. The magnitude of the EITC's impact on low birthweight
      rates suggests ecological effects, and an additional channel through which anti
      poverty measures can serve as public health interventions.

PMID- 29349232
TI  - Health and well-being at work: The key role of supervisor support.
AB  - This study aims to explore whether and in what way social support from different
      sources and domains makes an additional or different and independent contribution
      to various health and work-related outcomes. Cross-sectional data were used from
      an employee survey among the workforces of four service companies from different
      industries in Switzerland. The study sample covered 5,877 employees of working
      age. The lack of social support from a spouse, relatives, friends, direct
      supervisors, closest colleagues at work and other co-workers in case of problems
      at work and at home were assessed and studied individually and jointly as risk
      factors with respect to a total number of eight outcomes. Health-related outcomes
      covered poor self-rated health, musculoskeletal disorders, stress feelings and
      burnout symptoms. Work-related outcomes included feeling overwhelmed at work,
      difficulty with switching off after work, job dissatisfaction and intention to
      turnover. Social support from multiple sources in contrast to only individual
      sources in both life domains was found to be more frequent in women than in men
      and proved to be most protective and beneficial with regard to health and well
      being at work. However, after mutual adjustment of all single sources of social
      support from both domains, a lack of supervisor support turned out to be the only
      or the strongest of the few remaining support measures and statistically
      significant risk factors for the studied outcomes throughout and by far. Being
      unable to count on the support of a direct supervisor in case of problems at work
      and even at home was shown to involve a substantially increased risk of poor
      health and work-related outcomes (aOR = up to 3.8). Multiple sources of social
      support, and particularly supervisor support, seem to be important resources of
      health and well-being at work and need to be considered as key factors in
      workplace health promotion.

PMID- 29349233
TI  - Associations between household educational attainment and adolescent positive
      mental health in Canada.
AB  - Investigating the determinants of positive mental health, as opposed to focusing
      on mental illness, is a new research direction with important implications for
      population health promotion. Past research suggests that mental health develops
      in early childhood and that social factors including highest household
      educational attainment may play an important role. The current study examined the
      association between household educational attainment and adolescent self-reported
      positive mental health in a nationally representative Canadian sample using data
      from the 2011-12 Canadian Community Health Survey. The sample included 10,091
      adolescents aged 12 to19 living at home with at least one parent. Household
      educational attainment was obtained from a Statistics Canada derived variable
      documenting the highest level of education in the household. Adolescent positive
      mental health was assessed using the Mental Health Continuum scale. Multivariable
      logistic regression analyses showed that after adjusting for household income,
      single parent status, and household size, adolescents had lower odds of
      experiencing positive mental health in households in which attempted but not
      completed post-secondary was the highest education level compared to completed
      post-secondary education (OR = 0.64, 95% CI = 0.44, 0.95). This association was
      strongest in adolescents aged 12 to14 (OR = 0.43, 95% CI = 0.21, 0.84) and
      females (OR = 0.50, 95% CI = 0.29, 0.88). Contrary to expectations, we did not
      find an incremental increasing association between adolescent positive mental
      health and household educational attainment. Instead, results suggested that
      common underlying factors may have contributed both to uncompleted post-secondary
      education in the household and adolescents' diminished positive mental health.

PMID- 29349234
TI  - Adult health returns to education by key childhood social and economic
      indicators: Results from representative European data.
AB  - In the United States, associations between attained education and adult health
      typically are larger for those from disadvantaged childhood backgrounds. However,
      it remains unclear how specific key childhood indicators contribute to these
      adult health patterns, especially outside the United States. Drawing on the 2014
      European Social Survey (20 countries; N=31544), we investigate the key childhood
      and adolescent indicators of parental education, childhood financial strain, and
      any serious household conflict growing up, given how these early exposures are
      known to correlate strongly with both educational attainment and adult health. In
      regressions with country fixed effects, we find across Europe that higher levels
      of education are more strongly linked to lessened adult depressive symptoms when
      childhood disadvantage is present in terms of lower levels of parental education
      or higher childhood financial strain specifically. However, adjusted predictions
      reveal that childhood financial strain contributes to this heterogeneity in
      educational returns far more strongly than parental education. For self-rated
      health, only childhood financial strain enhances estimated educational health
      benefits when considering all key childhood social and economic factors jointly.
      Similarly, childhood financial strain in particular enhances educational
      protection against overall rates of disease in adulthood. Overall, our findings
      support prior work on United States data revealing higher educational health
      returns given childhood disadvantage. At the same time, our findings across three
      distinct adult health indicators suggest the particular importance of childhood
      financial strain to understanding heterogeneity in educational health returns.

PMID- 29349235
TI  - Social pathways to health: On the mediating role of the social network in the
      relation between socio-economic position and health.
AB  - Good health is one of the key qualities of life, but opportunities to be and
      remain healthy are unequally distributed across socio-economic groups. The
      beneficial health effects of the social network are well known. However, research
      on the social network as potential mediator in the pathway from socio-economic
      position (SEP) to health is scarce, while there are good reasons to expect a
      socio-economical patterning of networks. We aim to contribute to our
      understanding of socio-economic inequalities in health by examining the mediating
      role of structural and functional characteristics of the social network in the
      SEP-health relationship. Data were from the second wave of the Norwegian study on
      the life course, aging and generation study (NorLAG) and comprised 4534 men and
      4690 women aged between 40 and 81. We applied multiple mediation models to
      evaluate the relative importance of each network characteristic, and multiple
      group analysis to examine differences between middle-aged and older men and
      women. Our results indicated a clear socio-economical patterning of the social
      network for men and women. People with higher SEP had social networks that better
      protect against loneliness, which in turn lead to better health outcomes. The
      explained variance in health in older people by the social network and SEP was
      only half of the explained variance observed in middle-aged people, suggesting
      that other factors than SEP were more important for health when people age. We
      conclude that it is the function of the network, rather than the structure, that
      counts for health.

PMID- 29349236
TI  - The prevalence and correlates of suicidal behaviours (ideation, plan and attempt)
      among adolescents in senior high schools in Ghana.
AB  - Suicide is recognised as the third leading cause of death among adolescents
      globally. There is however limited data on the prevalence and factors associated
      with suicide particularly in Ghana. To explore the prevalence and risk and
      protective factors associated with suicide in Ghana, a nationwide Global School
      based Student Health Survey data collected among senior high school adolescents
      in Ghana was used. The prevalence of suicidal behaviours was 18.2%, 22.5% and
      22.2% for suicidal ideation, suicidal plan and suicidal attempt respectively. In
      the final analysis, anxiety increases the odds of suicidal behaviour, even after
      controlling for other variables. Loneliness increases the odds of suicidal
      behaviour but after adjusting for other factors the odds remained for only
      suicidal plan. Being bullied, physically attacked, involved in a physical fight
      and food insecurity remained risk factors for suicidal behaviour (i.e. ideation,
      plan and attempt) after adjusting for other factors. Truancy was found as a risk
      factor for both suicidal ideation and plans but such effect diminished for
      suicidal plan after adjusting for other variables. Increasing number of close
      friends remained a risk factor for both suicidal plan and attempt but such effect
      diminished for suicidal ideation after adjusting for other variables. Parental
      understanding of adolescents' problems and worries remained a significant
      protective factor for all the indices of suicidal behaviour after adjusting for
      other variables. Parental respect for privacy was protective of suicidal attempt
      but was not significant after adjusting for other variables. Early identification
      and intervention for at-risk adolescents in senior high schools, for example
      those experiencing different forms of physical abuse, drug and substance use and
      hunger can potentially reduce the prevalence of suicide among this population in
      Ghana.

PMID- 29349237
TI  - Social capital and pet ownership - A tale of four cities.
AB  - *Pet ownership is significantly associated with higher levels of social
      capital.*Social capital was associated with pet ownership in the U.S. and
      Australia.*Results are not confined to dog owners nor dog walkers.*Pets are an
      under-recognized conduit for building social capital.

PMID- 29349238
TI  - Engagement with health care providers as a mediator between social capital and
      quality of life among a sample of people living with HIV in the United States:
      Path-analysis.
AB  - Background: Social capital is "features of social organizations-networks, norms,
      and as trust that facilitate coordination and cooperation for mutual benefit".
      People with high social capital have lower mortality and better health outcomes.
      Although utilization of social networks has grown, social capital continues to be
      a complex concept in relation to health promotion. This study examined 1)
      associations between social capital and quality of life (QoL), 2) factors of
      social capital leading to higher QoL among people living with HIV (PLWH), 3) role
      of health care providers (HCP) as a mediator between social capital and QoL.
      Methods: This is a secondary analysis of the International Nursing HIV Network
      for HIV/AIDS Research. This cross-sectional study included 1673 PLWH from 11
      research sites in the United States in 2010. Using path analysis, we examined the
      independent effect of social capital on QoL, and the mediating effect of PLWH
      engagement with HCP. Results: The majority of participants were male (71.2%), and
      45.7% were African American. Eighty-nine percent of the participants were on
      antiretroviral therapy. Social capital consisted of three factors - social
      connection, tolerance toward diversity, and community participation - explaining
      87% of variance of social capital. Path analysis (RMSEA = 0, CFI = 1) found that
      social connection, followed by tolerance toward diversity, were the principal
      domain of social capital leading to better QoL (std. beta = 0.50, std. error =
      0.64, p<.05). Social capital was positively associated with QoL (p<.05). About
      11% of the protective effect of social capital on QoL was mediated by engagement
      with HCP (p<.05). Conclusions: This study emphasizes importance of social
      connections and mediating role of HCP in improving QoL for PLWH. To develop
      social capital effectively, interventions should focus on strengthening PLWH's
      social connections and engagement to HCP.

PMID- 29349239
TI  - The household food insecurity gradient and potential reductions in adverse
      population mental health outcomes in Canadian adults.
AB  - Purpose: Household food insecurity is related to poor mental health. This study
      examines whether the level of household food insecurity is associated with a
      gradient in the risk of reporting six adverse mental health outcomes. This study
      further quantifies the mental health impact if severe food insecurity, the
      extreme of the risk continuum, were eliminated in Canada. Methods: Using a pooled
      sample of the Canadian Community Health Survey (N = 302,683), we examined the
      relationship between level of food insecurity, in adults 18-64 years, and
      reporting six adverse mental health outcomes. We conducted a probit analysis
      adjusted for multi-variable models, to calculate the reduction in the odds of
      reporting mental health outcomes that might accrue from the elimination of severe
      food insecurity. Results: Controlling for various demographic and socioeconomic
      covariates, a food insecurity gradient was found in six mental health outcomes.
      We calculated that a decrease between 8.1% and 16.0% in the reporting of these
      mental health outcomes would accrue if those who are currently severely food
      insecure became food secure, after controlling for covariates. Conclusion:
      Household food insecurity has a pervasive graded negative effect on a variety of
      mental health outcomes, in which significantly higher levels of food insecurity
      are associated with a higher risk of adverse mental health outcomes. Reduction of
      food insecurity, particularly at the severe level, is a public health concern and
      a modifiable structural determinant of health worthy of macro-level policy
      intervention.

PMID- 29349240
TI  - Explaining racial/ethnic differences in all-cause mortality in the Multi-Ethnic
      Study of Atherosclerosis (MESA): Substantive complexity and hazardous working
      conditions as mediating factors.
AB  - Research on racial/ethnic health disparities and socioeconomic position has not
      fully considered occupation. However, because occupations are racially patterned,
      certain occupational characteristics may explain racial/ethnic difference in
      health. This study examines the role of occupational characteristics in
      racial/ethnic disparities in all-cause mortality. Data are from a U.S. community
      based cohort study (n=6342, median follow-up: 12.2 years), in which 893 deaths
      (14.1%) occurred. We estimated mortality hazard ratios (HRs) for African
      Americans, Hispanics, and Chinese Americans compared with whites. We also
      estimated the proportion of the HR mediated by each of two occupational
      characteristics, substantive complexity of work (e.g., problem solving,
      inductive/deductive reasoning on the job) and hazardous conditions (e.g., noise,
      extreme temperature, chemicals), derived from the Occupational Information
      Network database (O*NET). Analyses were adjusted for age, sex, nativity, working
      status at baseline, and study sites. African Americans had a higher rate of all
      cause death (HR 1.41; 95% confidence interval [CI]: 1.19-1.66) than whites.
      Chinese-American ethnicity was protective (HR 0.59, CI: 0.40-0.85); Hispanic
      ethnicity was not significantly different from whites (HR 0.88; CI: 0.67-1.17).
      Substantive complexity of work mediated 30% of the higher rate of death for
      African Americans compared with whites. For other groups, mediation was not
      significant. Hazardous conditions did not significantly mediate mortality in any
      racial/ethnic group. Lower levels of substantive complexity of work mediate a
      substantial part of the health disadvantage in African Americans. This job
      characteristic may be an important factor in explaining racial health
      disparities.

PMID- 29349241
TI  - Simultaneous evaluation of physical and social environmental correlates of
      physical activity in adults: A systematic review.
AB  - Background: Ecological models of physical activity posit that social and physical
      environmental features exert independent and interactive influences on physical
      activity, but previous research has focussed on independent influences. This
      systematic review aimed to synthesise the literature investigating how features
      of neighbourhood physical and social environments are associated with physical
      activity when both levels of influence are simultaneously considered, and to
      assess progress in the exploration of interactive effects of social and physical
      environmental correlates on physical activity. Methods: A systematic literature
      search was conducted in February 2016. Articles were included if they used an
      adult (>=15 years) sample, simultaneously considered at least one physical and
      one social environmental characteristic in a single statistical model, used self
      reported or objectively-measured physical activity as a primary outcome, reported
      findings from quantitative, observational analyses and were published in a peer
      reviewed journal. Combined measures including social and physical environment
      items were excluded as they didn't permit investigation of independent and
      interactive social and physical effects. Forty-six studies were identified.
      Results: An inconsistent evidence base for independent environmental correlates
      of physical activity was revealed, with some support for specific physical and
      social environment correlates. Most studies found significant associations
      between physical activity and both physical and social environmental variables.
      There was preliminary evidence that physical and social environmental variables
      had interactive effects on activity, although only 4 studies examined interactive
      effects. Conclusions: Inconsistent evidence of independent associations between
      environmental variables and physical activity could be partly due to unmeasured
      effect modification (e.g. interactive effects) creating unaccounted variance in
      relationships between the environment and activity. Results supported multiple
      levels of environmental influence on physical activity. It is recommended that
      further research uses simultaneous or interaction analyses to gain insight into
      complex relationships between neighbourhood social and physical environments and
      physical activity, as there is currently limited research in this area.

PMID- 29349242
TI  - The negative effects on mental health of being in a non-desired occupation in an
      increasingly precarious labour market.
AB  - Precarious employment has been associated with poor mental health. Moreover,
      increasing labour market precariousness may cause individuals to feel 'locked
      in', in non-desired workplaces or occupations, out of fear of not finding a new
      employment. This could be experienced as a 'loss of control', with similar
      negative health consequences. It is plausible that the extent to which being in a
      non-desired occupation (NDO) or being in precarious employment (PE) has a
      negative impact on mental health differs according to age group. We tested this
      hypothesis using data from 2331 persons, 18-34, 35-44, and 45-54 years old, who
      answered questionnaires in 1999/2000, 2005, and 2010. Incidence rate ratios (IRR)
      were calculated for poor mental health (GHQ-12) in 2010, after exposure to NDO
      and PE in 1999/2000 or 2005. NDO and PE were more common in the youngest age
      group, and they were both associated with poor mental health. In the middle age
      group the impact of NDO was null, while in contrast the IRR for PE was 1.7 (95%
      CI: 1.3-2.3) after full adjustment. The pattern was completely the opposite in
      the oldest age group (adjusted IRR for NDO 1.6 (1.1-2.4) and for PE 0.9 (0.6
      1.4)). The population attributable fraction of poor mental health was 14.2% and
      11.6%, respectively, for NDO in the youngest and oldest age group, and 17.2% for
      PE in the middle age group. While the consequences of PE have been widely
      discussed, those of NDO have not received attention. Interventions aimed at
      adapting work situations for older individuals and facilitating conditions of job
      change in such a way as to avoid risking unemployment or precarious employment
      situations may lead to improved mental health in this age group.

PMID- 29349243
TI  - Women's television watching and reproductive health behavior in Bangladesh.
AB  - Bangladesh has made significant social, economic, and health progress in recent
      decades, yet many reproductive health indicators remain weak. Access to
      television (TV) is increasing rapidly and provides a potential mechanism for
      influencing health behavior. We present a conceptual framework for the influence
      of different types of TV exposure on individual's aspirations and health behavior
      through the mechanisms of observational learning and ideational change. We
      analyze data from two large national surveys conducted in 2010 and 2011 to
      examine the association between women's TV watching and five reproductive health
      behaviors controlling for the effects of observed confounders. We find that TV
      watchers are significantly more likely to desire fewer children, are more likely
      to use contraceptives, and are less likely to have a birth in the two years
      before the survey. They are more likely to seek at least four antenatal care
      visits and to utilize a skilled birth attendant. Consequently, continued increase
      in the reach of TV and associated growth in TV viewing is potentially an
      important driver of health behaviors in the country.

PMID- 29349244
TI  - Trends in social inequality in physical inactivity among Danish adolescents 1991
      2014.
AB  - The aim of this study was to investigate social inequality in physical inactivity
      among adolescents from 1991 to 2014 and to describe any changes in inequality
      during this period. The analyses were based on data from the Danish part of the
      HBSC study, which consists of seven comparable cross-sectional studies of
      nationally representative samples of 11-15-year old adolescents. The available
      data consisted of weekly time (hours) spent on vigorous physical activity and
      parental occupation from 30,974 participants. In summary, 8.0% of the adolescents
      reported to be physically inactive, i.e. spend zero hours of vigorous leisure
      time physical activity per week. The proportion of physically inactive
      adolescents was 5.4% in high social class and 7.8% and 10.8%, respectively, in
      middle and low social class. The absolute social inequality measured as
      prevalence difference between low and high social class did not change
      systematically across the observation period from 1991 to 2014. Compared to high
      social class, OR (95% CI) for physical inactivity was 1.48 (1.32-1.65) in middle
      social class and 2.18 (1.92-2.47) in lower social class. This relative social
      inequality was similar in the seven data collection waves (p=0.971). Although the
      gap in physical inactivity between social classes does not seem to be widening in
      Danish adolescents, there are still considerable differences in the activity
      levels between high, middle and low social class adolescents. Consequently, there
      is a need for a targeted physical activity intervention among adolescents from
      low (and middle) social class.

PMID- 29349245
TI  - Mental health of sub-saharan african migrants: The gendered role of migration
      paths and transnational ties.
AB  - In Europe, migrants are at higher risk of common mental disorders or
      psychological distress than are natives. Little is known regarding the social
      determinants of migrant mental health, particularly the roles played by migration
      conditions and transnational practices, which may manifest themselves in
      different ways for men and for women. The goal of this paper was to understand
      the gendered roles of migration paths and transnational ties in mental health
      among sub-Saharan African migrants residing in the Paris, France, metropolitan
      area. This study used data from the Parcours study conducted in 2012-2013, which
      employed a life-event approach to collect data from a representative sample of
      migrants who visited healthcare facilities (n = 2468). We measured anxiety and
      depressive symptoms at the time of data collection with the Patient Health
      Questionnaire-4 (PHQ-4). Reasons for migration, the living conditions in the host
      country and transnational ties after migration were taken into account by sex and
      after adjustment. Our study demonstrates that among sub-Saharan African migrants,
      mental health is related to the migratory path and the migrant's situation in the
      host country but differently for women and men. Among women, anxiety and
      depressive symptoms were strongly related to having left one's home country
      because of threats to one's life. Among men, residing illegally in the host
      country was related to impaired mental health. For both women and men, cross
      border separation from a child less than 18 years old was not independently
      associated with anxiety and depressive symptoms. In addition, social and
      emotional support from relatives and friends-both from the society of origin and
      of destination-were associated with lower anxiety and depressive symptoms.
      Migrant mental health may be impaired in the current context of anti-migrant
      policies and an anti-immigrant social environment in Europe.

PMID- 29349246
TI  - Feasibility of a novel participatory multi-sector continuous improvement approach
      to enhance food security in remote Indigenous Australian communities.
AB  - Background: Food insecurity underlies and compounds many of the development
      issues faced by remote Indigenous communities in Australia. Multi-sector
      approaches offer promise to improve food security. We assessed the feasibility of
      a novel multi-sector approach to enhance community food security in remote
      Indigenous Australia. Method: A longitudinal comparative multi-site case study,
      the Good Food Systems Good Food for All Project, was conducted (2009-2013) with
      four Aboriginal communities. Continuous improvement meetings were held in each
      community. Data from project documents and store sales were used to assess
      feasibility according to engagement, uptake and sustainability of action, and
      impact on community diet, as well as identifying conditions facilitating or
      hindering these. Results: Engagement was established where: the community
      perceived a need for the approach; where trust was developed between the
      community and facilitators; where there was community stability; and where
      flexibility was applied in the timing of meetings. The approach enabled
      stakeholders in each community to collectively appraise the community food system
      and plan action. Actions that could be directly implemented within available
      resources resulted from developing collaborative capacity. Actions requiring
      advocacy, multi-sectoral involvement, commitment or further resources were less
      frequently used. Positive shifts in community diet were associated with key areas
      where actions were implemented. Conclusion: A multi-sector participatory approach
      seeking continuous improvement engaged committed Aboriginal and non-Aboriginal
      stakeholders and was shown to have potential to shift community diet. Provision
      of clear mechanisms to link this approach with higher level policy and decision
      making structures, clarity of roles and responsibilities, and processes to
      prioritise and communicate actions across sectors should further strengthen
      capacity for food security improvement. Integrating this approach enabling local
      decision-making into community governance structures with adequate resourcing is
      an imperative.

PMID- 29349247
TI  - Incorporating biomarkers into the study of socio-economic status and health among
      older adults in China.
AB  - The social gradient in health - that individuals with lower SES have worse health
      than those with higher SES- is welldocumented using self-reports of health in
      more developed countries. Less is known about the relationship between SES and
      health biomarkers among older adults residing in less developed countries. We use
      data from the ChineseLongitudinal Healthy Longevity Survey (CLHLS) longevity
      areas sub-sample to examine the social gradient in healthamong rural young-old
      and oldest-old adults (N=2,121). Our health indicators include individual
      biomarkers, metabolic syndrome, and self-reports of health. We found a largely
      positive relationship between SES and health. SES was more consistently
      associated with individual biomarkers among the oldest-old than the young-old,
      providing evidence for cumulative disadvantage. We discuss the implications of
      our findings for older adults who have lived through different social, economic,
      and health regimes.

PMID- 29349248
TI  - Association of financial hardship with poor sleep health outcomes among men who
      have sex with men.
AB  - Previous studies have identified an association between socioeconomic status and
      sleep health. While some research has studied this association among sexual
      minority groups, including men who have sex with men (MSM), they exclusively
      focused on US-based populations. The interplay between the two in shaping sleep
      health has not been previously examined on populations residing outside the US.
      This study considers both determinants, by investigating whether financial
      hardship is associated with sleep health among a sample of MSM in Paris, France.
      Broadcast advertisements were placed on a popular geosocial-networking smartphone
      application for MSM to direct users in Paris to a web-based survey measuring
      financial hardship and five dimensions of sleep health as well as socio
      demographic characteristics. Modified Poisson models with robust error variance
      were computed to estimate risk ratios (RRs) and 95% confidence intervals (CI) for
      the associations between financial hardship and the following self-reported
      outcomes: 1) poor sleep quality, 2) short sleep duration; and 3) sleep problems.
      In total, 580 respondents completed the survey. In this sample, both financial
      hardship and poor sleep health were common - 45.5% reported that it was
      extremely, very, or somewhat difficult for them to meet their monthly payments on
      bills (referred to as "high financial hardship") and 30.1% rated their sleep as
      fairly bad or very bad (referred to as "poor sleep quality"). Multivariate models
      revealed that, compared to participants who reported low financial hardship,
      those who reported high financial hardship were more likely to report poor sleep
      quality (aRR: 1.35, 95% CI: 1.04, 1.77), to report problems falling asleep (aRR:
      1.23, 95% CI: 1.02, 1.49), and to report problems staying awake in the daytime
      (aRR: 3.12, 95% CI: 1.83, 5.31). Future research should investigate whether this
      relationship is causal and determine whether interventions to reduce financial
      hardships could promote sleep health among MSM.

PMID- 29349249
TI  - The differential effects of rural health care access on race-specific mortality.
AB  - We examined the relationship between race-specific rural mortality and the health
      infrastructure of rural counties in light of America's recent emergence of a
      rural mortality penalty. Using the Compressed Mortality File from National Center
      for Health Statistics (2008-2012) and county-level demographic, socioeconomic,
      and health care indicators from the Area Health Resource File and the US Census,
      we created a rural public health infrastructure index which encompasses four
      types of health care access (public health employees, critical access
      hospital/rural referral centers, rural health clinics, and emergency departments)
      within counties. We found that each unit increase in the index is associated with
      a decline in rural Black mortality, but is associated with an increase in rural
      White mortality. Policymakers could benefit from focusing on the declining rate
      of mortality improvement in many rural regions, specifically by trying to better
      understand how decisions concerning public health spending may influence
      mortality differently for Black and White residents.

PMID- 29349250
TI  - Best-worst scaling survey of preferences regarding the adverse effects of tobacco
      use in China.
AB  - We use best-worst scaling to assess two types of concern levels of the adverse
      consequences of smoking in China. While the smoking cessation policy has worked
      well in Taiwan, more than 1 million people in mainland China are estimated to die
      every year from tobacco use. This study compares the preferences of Chinese
      individuals in the two jurisdictions (mainland versus Taiwan) and explores the
      possibility of information-based interventions. The relative importance of 13
      adverse effects was assessed by conducting a web-based survey on a sample of 480
      Chinese participants. The 13 items consist of various adverse effects of tobacco
      use: from long-term health risk, such as lung cancer and cardiovascular diseases,
      to reduction of physical capacity and sexual dysfunction, and disturbance to non
      smokers. The resulting data suggest possible strategies to curb smoking. Subgroup
      analysis, focusing on gender, smoking status, and nicotine dependence, was also
      conducted. Lung cancer, cardiovascular diseases, and chronic obstructive
      pulmonary disease, in this order, rank highest for both types of respondents. On
      the other hand, high expenditures (13th) and weight gain after cessation (12th)
      are the lowest ranked for both. Measuring individual best-worst scores reveals
      substantial heterogeneity among respondents and that information-based
      intervention can help curb smoking.

PMID- 29349251
TI  - Undiagnosed depression: A community diagnosis.
AB  - Many large provider networks are investing heavily in preventing disease within
      the communities that they serve. We explore the potential benefits and challenges
      associated with tackling depression at the community level using a unique dataset
      designed for one such provider network. The economic costs of having depression
      (increased medical care use, lower quality of life, and decreased workplace
      productivity) are among the highest of any disease. Depression often goes
      undiagnosed, yet many believe that depression can be treated or prevented
      altogether. We explore the prevalence, distribution, economic burden, and the
      psychosocial and economic factors associated with undiagnosed depression in a
      lower-income neighborhood in northern Manhattan. Even using state-of-the art data
      to "diagnose" the risk factors within a community, it can be challenging for
      provider networks to act against such risk factors.

PMID- 29349252
TI  - Wealth, justice and freedom: Objective and subjective measures predicting poor
      mental health in a study across eight countries.
AB  - Background: Macro-level factors (MF) such as wealth, justice and freedom measured
      with objective country-level indicators (objective MF), for instance the Gross
      Domestic Product (GDP), have been investigated in relation to health and well
      being, but rarely in connection with depression, anxiety and stress subsumed as
      poor mental health. Also, a combination of different objective MF and of how
      individuals perceive those MF (subjective MF) has not been taken into
      consideration. In the present study, we combined subjective and objective
      measures of wealth, justice and freedom and examined their relationship with poor
      mental health. Method: Population-based interviews were conducted in France,
      Germany, Poland, Russia, Spain, Sweden, U.K. and U.S.A. (n ~ 1000 per country).
      GDP, GINI coefficient, Justice Index and Freedom Index were used as objective MF,
      whereas subjective MF were perceived wealth, justice and freedom measured at the
      individual level. Poor mental health was assessed as a combination of symptoms of
      depression, anxiety and stress. Results: In a random-intercept-model, GINI
      coefficient and Freedom Index were significant positive country-level, and
      perceived wealth, justice, and freedom significant negative individual-level
      predictors of symptoms of poor mental health. Conclusion: Multiple subjective and
      objective MF should be combined to assess the macrosystem's relationship with
      poor mental health more precisely. The relationship between MF and poor mental
      health indicates that the macrosystem should be taken into account as relevant
      context for mental health problems, too.

PMID- 29349253
TI  - Recreational marijuana legalization and college student use: Early evidence.
AB  - We analyze marijuana use by college undergraduates before and after legalization
      of recreational marijuana. Using survey data from the National College Health
      Assessment, we show that students at Washington State University experienced a
      significant increase in marijuana use after legalization. This increase is larger
      than would be predicted by national trends. The change is strongest among
      females, Black students, and Hispanic students. The increase for underage
      students is as much as for legal-age students. We find no corresponding changes
      in the consumption of tobacco, alcohol, or other drugs.

PMID- 29349254
TI  - Prevalence of psychological distress and its association with socio-demographic
      and HIV-risk factors in South Africa: Findings of the 2012 HIV prevalence,
      incidence and behaviour survey.
AB  - Background: In South Africa, there are limited nationally representative data on
      the prevalence and factors associated with psychological distress. This study
      used a 2012 nationally representative population-based household survey to
      investigate factors associated with psychological distress in South Africa.
      Methods: The survey is based on a multistage stratified cross-sectional design.
      Univariate and multivariate logistic regression models were fitted to identify
      factors associated with psychological distress. Results: Out of a total 25860
      participants, 23.9% reported psychological distress. Higher likelihood of
      reporting psychological distress was significantly associated with being female
      [OR = 1.68 (95% CI: 1.34-2.10), p < 0.001], aged 25 to 49 years [OR = 1.35 (95%
      CI: 1.08-1.70), p = 0.010] and 50 years and older [OR = 1.44 (95% CI: 1.06-1.97),
      p = 0.023)], Black Africans [OR = 1.61 (95% CI: 1.24-2.10), p < 0.001)], a high
      risk drinker [OR = 1.37 (95% CI: 1.02-1.83), p = 0.037], a hazardous drinker [OR
      = 4.76 (95% CI: 2.69-8.42), p < 0.001] and HIV positive, [OR = 1.79 (95% CI:1.55
      2.08) p < 0.001], while lower likelihood of reporting psychological distress was
      significantly associated with being married [OR = 0.78 (95% CI: 0.62-0.98), p =
      0.031), employed [OR = 0.71 (95% CI: 0.57-0.88), p = 0.002], and living in a
      rural formal area [OR = 0.73 (95% CI: 0.55-0.97), p = 0.033]. Conclusion: There
      is a need to develop strategies to alleviate psychological distress in the
      general population, with a particular focus on those who may be more vulnerable
      to distress such as females, the aged, excessive alcohol users, the unemployed,
      people living with HIV and those residing in urban areas as identified in the
      current findings.

PMID- 29349255
TI  - Gender-specific associations between involvement in team sport culture and
      canadian adolescents' substance-use behavior.
AB  - Canadian adolescents have some of the highest rates of substance use in the
      world. The etiology of this phenomenon has not been fully explored, and one
      possible contextual determinant is involvement in sport activities that foster
      risk-taking behaviors through physical and social mechanisms. Using the 2013-14
      Health Behaviour in School Aged Children (HBSC) study we therefore examined this
      hypothesis in a contemporary national sample of Canadian adolescents. The
      strength and direction of the relationship between sport and substance use varied
      by gender and substance, with team sport participation associated with increased
      binge drinking (RR 1.33 [95% CI 1.13-1.56] for boys, RR 1.21 [1.06-1.38] for
      girls) and use of smokeless tobacco (RR 1.68 [1.34-2.10] for boys, RR 1.32 [1.01
      1.72] for girls), but with lower prevalence levels of cannabis use (RR 0.73 [95%
      CI 0.61-0.88]) and cigarette smoking (RR 0.79 [95% CI 0.70-0.89]) in girls alone.
      We also compared team sport athletes with high social involvement (sports team as
      primary peer group) and physical involvement (higher number of days/week
      physically active) to those with low involvement. For boys, the combination of
      high physical and high social involvement was associated with the highest risk,
      while high social involvement alone was associated with the greatest risk for
      girls. While team sport participation confers only a small increased risk for
      substance use, the prevalence of sport participation results in a large
      population impact. Given this fact, interventions such as education for parents
      and coaches and policies encouraging engagement in a variety of extracurricular
      activities should be explored.

PMID- 29349256
TI  - Income and the mental health of Canadian mothers: Evidence from the Universal
      Child Care Benefit.
AB  - The Universal Child Care Benefit, introduced in 2006, was an income transfer for
      Canadian families with young children. I exploit this exogenous increase in
      income to answer the following questions: (1) Is there a relationship between
      income and mental health among Canadian mothers? (2) Is it corroborated by other
      measures of well-being (i.e. stress, life satisfaction)? (3) Is the effect
      different for lone mothers compared to those in two-parent families? I answer
      these questions using a difference-in-differences model and microdata from the
      Canadian Community Health Survey, 2003 to 2008. The estimating sample includes
      26,886 mothers, 6273 of whom are lone parents. I find the income transfer
      improved mental health and life satisfaction regardless of family structure,
      albeit not necessarily for a given individual. Rather, average scores were higher
      for mothers with young children after implementation of the Universal Child Care
      Benefit. For example, they were more likely to report 'excellent' mental health
      and less likely to be in each of the other categories. The transfer also reduced
      stress among lone mothers with young children. Specifically, they were less
      likely to be 'quite a bit' or 'extremely' stressed on a daily basis, and more
      likely to be 'not at all' or 'not very' stressed. I argue that assumptions of the
      model are plausible and show that results are consistent across several
      robustness checks.

PMID- 29349257
TI  - The tyranny of the averages and the indiscriminate use of risk factors in public
      health: The case of coronary heart disease.
AB  - Modern medicine is overwhelmed by a plethora of both established risk factors and
      novel biomarkers for diseases. The majority of this information is expressed by
      probabilistic measures of association such as the odds ratio (OR) obtained by
      calculating differences in average "risk" between exposed and unexposed groups.
      However, recent research demonstrates that even ORs of considerable magnitude are
      insufficient for assessing the ability of risk factors or biomarkers to
      distinguish the individuals who will develop the disease from those who will not.
      In regards to coronary heart disease (CHD), we already know that novel biomarkers
      add very little to the discriminatory accuracy (DA) of traditional risk factors.
      However, the value added by traditional risk factors alongside simple demographic
      variables such as age and sex has been the subject of less discussion. Moreover,
      in public health, we use the OR to calculate the population attributable fraction
      (PAF), although this measure fails to consider the DA of the risk factor it
      represents. Therefore, focusing on CHD and applying measures of DA, we re-examine
      the role of individual demographic characteristics, risk factors, novel
      biomarkers and PAFs in public health and epidemiology. In so doing, we also raise
      a more general criticism of the traditional risk factors' epidemiology. We
      investigated a cohort of 6103 men and women who participated in the baseline
      (1991-1996) of the Malmo Diet and Cancer study and were followed for 18 years. We
      found that neither traditional risk factors nor biomarkers substantially improved
      the DA obtained by models considering only age and sex. We concluded that the PAF
      measure provided insufficient information for the planning of preventive
      strategies in the population. We need a better understanding of the individual
      heterogeneity around the averages and, thereby, a fundamental change in the way
      we interpret risk factors in public health and epidemiology.

PMID- 29349258
TI  - Neighborhood context and birth outcomes: Going beyond neighborhood disadvantage,
      incorporating affluence.
AB  - *Neighborhood affluence protects against the risk of poor birth outcome. *The
      protective effect of affluence holds for Whites, Blacks, Hispanics and Asians.
      *Mediation of these pathways by prenatal smoking varies by racial group. *The
      discourse on neighborhoods and birth outcomes should include affluence.

PMID- 29349259
TI  - Access and quality of parks and associations with obesity: A cross-sectional
      study.
AB  - Public health is increasingly engaging with multi-faceted obesity prevention
      efforts. Although parks represent key community assets for broader public health,
      they may not be distributed equitably and associations with obesity are
      equivocal. We investigated park access and quality relative to deprivation and
      obesity with individual-level data from the Yorkshire Health Study. Compared to
      the least deprived areas, the moderately and most deprived areas had a greater
      park access and park quality in terms of features and amenities. However, parks
      in the moderately and most deprived areas also had the most safety concerns and
      incivilities. Although deprivation was associated with obesity, contrary to
      current policy guidance, both park access and quality appear less important for
      understanding variations in obesity within this study. Although sub-group
      analyses by deprivation tertile revealed that low quality park amenities in
      highly and moderately deprived areas may be important for understanding obesity
      prevalence, all other associations were non-significant.

PMID- 29349260
TI  - Environmental radiation level, radiation anxiety, and psychological distress of
      non-evacuee residents in Fukushima five years after the Great East Japan
      Earthquake: Multilevel analyses.
AB  - The present study aimed to clarify the associations among radiation exposure or
      psychological exposure to the Fukushima nuclear power plant accident (i.e.,
      fear/anxiety immediately after the accident), current radiation anxiety, and
      psychological distress among non-evacuee community residents in Fukushima five
      years after the Great East Japan Earthquake, which occurred in March 2011. A
      questionnaire survey was administered to a random sample of non-evacuee community
      residents from 49 municipalities of Fukushima prefecture from February to April
      2016, and data from 1684 respondents (34.4%) were analyzed. Environmental
      radiation levels at the time of the accident were ascertained from survey meter
      data, while environmental radiation levels at the time of the survey were
      ascertained from monitoring post data. In the questionnaire, immediate
      fear/anxiety after the accident, current radiation anxiety, and psychological
      distress were measured using a single-item question, a 7-item scale, and K6,
      respectively. Multilevel linear or logistic regression models were applied to
      analyze the determinants of radiation anxiety and psychological distress. The
      findings showed that environmental radiation levels at the time of the survey
      were more strongly associated with radiation anxiety than radiation levels
      immediately after the accident. Disaster-related experiences, such as direct
      damage, disaster-related family stress, and fear/anxiety after the accident, and
      demographic characteristics (e.g., younger age, being married, low socioeconomic
      status) were significantly associated with radiation anxiety. Environmental
      radiation levels at the time of the accident or survey were not significantly
      associated with psychological distress. Radiation anxiety largely mediated the
      association between fear/anxiety after the accident and psychological distress.
      In addition to environmental radiation levels, respondents' radiation anxiety was
      affected by multiple factors, such as disaster-related experiences and
      demographic characteristics. Radiation levels were not associated with
      psychological distress in non-evacuee community residents. Rather, fear/anxiety
      after the nuclear power plant accident may be a determinant of psychological
      distress, mediated by radiation anxiety.

PMID- 29349261
TI  - The impact of the UK National Minimum Wage on mental health.
AB  - Despite an emerging literature, there is still sparse and mixed evidence on the
      wider societal benefits of Minimum Wage policies, including their effects on
      mental health. Furthermore, causal evidence on the relationship between earnings
      and mental health is limited. We focus on low-wage earners, who are at higher
      risk of psychological distress, and exploit the quasi-experiment provided by the
      introduction of the UK National Minimum Wage (NMW) to identify the causal impact
      of wage increases on mental health. We employ difference-in-differences models
      and find that the introduction of the UK NMW had no effect on mental health. Our
      estimates do not appear to support earlier findings which indicate that minimum
      wages affect mental health of low-wage earners. A series of robustness checks
      accounting for measurement error, as well as treatment and control group
      composition, confirm our main results. Overall, our findings suggest that
      policies aimed at improving the mental health of low-wage earners should either
      consider the non-wage characteristics of employment or potentially larger wage
      increases.

PMID- 29349262
TI  - Mothers' labor market choices and child development outcomes in Chile.
AB  - This paper examines associations between labor market participation of Chilean
      mothers and the cognitive, language, and socio-economic development of their
      children. Using a nationally-representative sample of 3-year-old children, we
      test if mothers' work intensity in the two previous years is associated with
      child development outcomes; data were collected in 2010 when children were one
      year old, and again in 2012, when they were three years old. We find that
      children who were three years old with mothers who worked for higher fractions of
      their children's lives in the previous two years perform significantly better on
      all tests (cognitive, language, socio-emotional) than children whose mothers had
      worked less, while controlling for baseline test performance. These main effects
      did not remain significant with the inclusion of a wide range of socio-economic,
      demographic control variables, however. Our results were similarly null when
      using an IV analysis or a propensity score matching approach. We provide
      descriptive information on theoretical pathways by which maternal work may
      influence child development. Though several of these pathways (e.g. preschool,
      toys, maternal stress) seem to be associated with both maternal work and child
      development outcomes, the pathways are not sufficiently strong to generate an
      association between maternal work and child development. We conclude that Chilean
      mothers' employment in early childhood generally does not have an effect on child
      development.

PMID- 29349263
TI  - Worldviews and trust of sources for health information on electronic nicotine
      delivery systems: Effects on risk perceptions and use.
AB  - Public health agencies, the news media, and the tobacco/vapor industry have
      issued contradictory statements about the health effects of electronic nicotine
      delivery systems (ENDS). We investigated the levels of trust that consumers place
      in different information sources and how trust is associated with cultural
      worldviews, risk perceptions, ENDS use, and sociodemographic characteristics
      using a nationally representative sample of 6051 U.S. adults in 2015. Seventeen
      percent of adults were uncertain about their trust for one or more potential
      sources. Among the rest, the Centers for Disease Control and Prevention (CDC),
      health experts, and the Food & Drug Administration (FDA) elicited the highest
      levels of trust. In contrast, tobacco and vapor manufacturers, vape shop
      employees, and, to a lesser extent, the news media were distrusted. Adults who
      had higher incomes and more education or espoused egalitarian and communitarian
      worldviews expressed more trust in health sources and the FDA, whereas those
      identifying as non-Hispanic Black or multiracial reported less trust. Current
      smokers, those who identified as non-Hispanic Black or other race, had lower
      incomes, and espoused hierarchy and individualism worldviews expressed less
      distrust toward the tobacco and vapor industry. Greater trust (or less distrust)
      toward the tobacco and vapor industry and an individualism worldview were
      associated with perceptions of lower risk of premature death from daily ENDS use,
      greater uncertainty about those risks, and greater odds of using ENDS. Public
      health and the FDA should consider consumer trust and worldviews in the design
      and regulation of public education campaigns regarding the potential health risks
      and benefits of ENDS.

PMID- 29349264
TI  - Life course influences on later life health in China: Childhood health exposure
      and socioeconomic mediators during adulthood.
AB  - China's unprecedented population aging and social and economic change raise
      important issues concerning life course determinants of advantage or disadvantage
      into later life. Data from the China Health and Retirement Longitudinal Study
      (CHARLS) 2013 were analysed to identify the influence of childhood health on
      later life health as indicated by self-rated health and how this influence could
      be mediated by social and economic positions (SEP) and resources later in the
      life span. CHARLS provides nationally representative data on 18, 000 individuals
      aged 45 years and above in approximately 150 districts and 450 villages. Both
      multivariate logit regression model and KHB method (Karlson/Holm/Breen method)
      were applied to examine and decompose the life span influences on later life
      health. The results show that the childhood health, accounts for approximately
      half of the effect directly and another half of the effect indirectly through
      social and economic variations during adulthood. Relative living standard,
      marital status and urban residence are the most significant and important social
      and economic mediators for men; For women, living standard and secondary
      schooling are most influential while marital status is not significant.
      Implications for social and economic policies to improve later life health are
      discussed.

PMID- 29349265
TI  - Children's migration and chronic illness among older parents 'left behind' in
      China.
AB  - The relationship between adult children's migration and the health of their older
      parents 'left behind' is an emerging research area and existing studies reflect
      mixed findings. This study aims to investigate the association between having
      migrant (adult) children and older parents' chronic illness in China, using
      chronic stomach or other digestive diseases as a proxy. Secondary analysis of the
      national baseline survey of the 2011 China Health and Retirement Longitudinal
      Study (CHARLS) was conducted. Analyses were conducted in a total of sample of
      6495 individuals aged 60 years and above from 28 out of 31 provinces in China,
      who had at least one child at the baseline survey. Binary logistic regression was
      used. The prevalence of any of the diagnosed conditions of chronic stomach or
      other digestive diseases was higher among older people with a migrant son than
      among those without (27 percent vs 21 percent, p < 0.001). More specifically, the
      odds ratio of reporting a disease was higher among older adults with at least one
      adult son living in another county or province than among those with all their
      sons living closer (OR = 1.29, 95% CI = 1.10-1.51). The results from this large
      sample of older adults support the hypothesis that migration of sons
      significantly increases the risk of chronic stomach and other digestive diseases
      among 'left behind' elderly parents in contemporary China.

PMID- 29349266
TI  - Can we determine whether physical limitations are more prevalent in the US than
      in countries with comparable life expectancy?
AB  - We evaluate the variability in estimates of self-reported physical limitations by
      age across four nationally representative surveys in the US. We consider its
      implications for determining whether, as previous literature suggests, the US
      estimates reveal limitations at an earlier age than in three countries with
      similar life expectancy: England, Taiwan, and Costa Rica. Based on cross
      sectional data from seven population-based surveys, we use local mean smoothing
      to plot self-reported limitations by age for each of four physical tasks for each
      survey, stratified by sex. We find substantial variation in the estimates in the
      US across four nationally-representative surveys. For example, one US survey
      suggests that American women experience a walking limitation 15 years earlier
      than their Costa Rican counterparts, while another US survey implies that
      Americans have a 4-year advantage. Differences in mode of survey may account for
      higher prevalence of limitations in the one survey that used a self-administered
      mail-in questionnaire than in the other surveys that used in-person or telephone
      interviews. Yet, even among US surveys that used the same mode, there is still so
      much variability in estimates that we cannot conclude whether Americans have
      better or worse function than their counterparts in the other countries.
      Seemingly minor differences in question wording and response categories may
      account for the remaining inconsistency. If minor differences in question wording
      can result in such extensive variation in the estimates within a given
      population, then lack of comparability is likely to be an even greater problem
      when examining results across countries that do not share the same language or
      culture. Despite the potential utility of self-reported physical function within
      a survey sample, our findings imply that absolute estimates of population-level
      prevalence of self-reported physical limitations are unlikely to be strictly
      comparable across countries-or even across surveys within the same population.

PMID- 29349267
TI  - Subjective health and well-being: Toward robust cross-cultural comparisons.

PMID- 29349269
TI  - Fertility behaviors in South Korea and their association with ultrasound prenatal
      sex screening.
AB  - Imbalances in the sex ratio at birth in Southeast and East Asia increased
      especially after the mid-1980s. We study how ultrasonic technology affected sex
      ratios at birth in South Korea, a country with a strong son preference. Between
      1985 and 1995 fetal screenings and abortion services were widely available,
      though not available in the years before, and prohibited in the years after.
      Using the 1985, 1995, and 2005 Census microdata, we examine changes in sex ratios
      of newborns by birth year. We then study periodic effects on the fertility
      stopping rule, using the 2006 Korean Longitudinal Study of Aging, which provides
      birth years for all children. Between 1985 and 1995 there was a large increase in
      the fraction of boy babies at birth orders of three or more. Despite these
      fractions falling in the subsequent time period when fetal screening became
      illegal, they remained above plausible biological levels. Supporting earlier
      findings in the literature, the increase in sex ratios was especially large when
      prior sibling composition was entirely female. We also find that having only
      daughters significantly increases the probability of parents having another
      child, and this effect is greater for parents with any child born after 1985 than
      the parents with all children born before 1985. There exist significant period
      effects, suggesting that sex ratios at birth became imbalanced when ultrasound
      technology became available. The availability of ultrasound technology also
      influenced parents' fertility decisions, seen especially in parents with only
      daughters deciding to have another child. Our study provides new evidence for how
      the availability of ultrasound technology influenced sex ratios at birth and
      influenced fertility behaviors in Korea.

PMID- 29349268
TI  - Socioeconomic status indicators and common mental disorders: Evidence from a
      study of prenatal depression in Pakistan.
AB  - There is growing interest in the relationship between socioeconomic status (SES),
      poverty, and mental health in low and middle-income countries (LMIC). However, it
      is not clear whether a gradient approach focused on a wider SES distribution or a
      binary poverty approach is more salient for mental health in LMIC. Yet this
      distinction has implications for interventions aimed at improving population
      health. We contribute to the literature by examining how multiple indicators of
      socioeconomic status, including gradient SES and binary poverty indicators,
      contribute to prenatal depression symptoms in a LMIC context. Prenatal depression
      is an important public health concern with negative sequela for the mother and
      her children. We use data on assets, education, food insecurity, debt, and
      depression symptoms from a sample of 1154 pregnant women residing in rural
      Pakistan. Women who screened positive for depression participated in a cluster
      randomized controlled trial of a perinatal depression intervention; all women
      were interviewed October 2015-February 2016, prior to the start of the
      intervention. Cluster-specific sampling weights were used to approximate a random
      sample of pregnant women in the area. Findings indicate that fewer assets,
      experiencing food insecurity, and having household debt are independently
      associated with worse depression symptoms. The association with assets is linear
      with no evidence of a threshold effect, supporting the idea of a gradient in the
      association between levels of SES and depression symptoms. A gradient was also
      initially observed with woman's educational attainment, but this association was
      attenuated once other SES variables were included in the model. Together, the
      asset, food insecurity, and debt indicators explain 14% of the variance in
      depression symptoms, more than has been reported in high income country studies.
      These findings support the use of multiple SES indicators to better elucidate the
      complex relationship between socioeconomic status and mental health in LMIC.

PMID- 29349270
TI  - Breaking down the monolith: Understanding flu vaccine uptake among African
      Americans.
AB  - Black adults are significantly less likely to be immunized for seasonal influenza
      when compared to Whites. This persistent disparity contributes to increased
      influenza-related morbidity and mortality in the African American population.
      Most scholarship on vaccine disparities has compared Whites and Blacks. Employing
      Public Health Critical Race Praxis, this study seeks to shift the focus to
      explore differences within the Black population. Utilizing a nationally
      representative 2015 survey of US Black adults (n = 806), we explore differences
      by gender, age, income, and education across vaccine-related measures (e.g.,
      perceived risk, knowledge, attitudes) and racial factors (e.g. racial salience,
      racial fairness, perceived discrimination). We also explore differences by
      vaccine behavior in the past five years among those who vaccinate every year,
      most years but not all, once or twice, and never. Greater frequency of flu
      vaccine uptake was associated with better self-reported vaccine knowledge, more
      positive vaccine attitudes, more trust in the flu vaccine and the vaccine
      process, higher perceived disease risk, lower perceived risk of vaccine side
      effects, stronger subjective and moral norms, lower general vaccine hesitancy,
      higher confidence in the flu vaccine, and lower perceived barriers. Logistic
      regression results highlighted other significant differences among the groups,
      emphasizing areas to target for improved vaccination rates. We find great
      diversity within the Black community related to influenza immunization decisions,
      highlighting the need to "break down the monolith" in future research.

PMID- 29349271
TI  - Becoming a 'pharmaceutical person': Medication use trajectories from age 26 to 38
      in a representative birth cohort from Dunedin, New Zealand.
AB  - Despite the abundance of medications available for human consumption, and
      frequent concerns about increasing medicalization or pharmaceuticalization of
      everyday life, there is little research investigating medicines-use in young and
      middle-aged populations and discussing the implications of young people using
      increasing numbers of medicines and becoming pharmaceutical users over time. We
      use data from a New Zealand longitudinal study to examine changes in self
      reported medication use by a complete birth cohort of young adults. Details of
      medications taken during the previous two weeks at age 38 are compared to similar
      data collected at ages 32 and 26, and by gender. Major drug categories are
      examined. General use profiles and medicine-types are considered in light of our
      interest in understanding the formation of the young and middle-aging
      'pharmaceutical person' - where one's embodied experience is frequently and
      normally mediated by pharmaceutical interventions having documented benefit/risk
      outcomes.

PMID- 29349272
TI  - Why is parental lifespan linked to children's chances of reaching a high age? A
      transgenerational hypothesis.
AB  - Purpose: Transgenerational determinants of longevity are poorly understood. We
      used data from four linked generations (G0, G1, G2 and G3) of the Uppsala Birth
      Cohort Multigeneration Study to address this issue. Methods: Mortality in G1 (N =
      9565) was followed from 1961-2015 and analysed in relation to tertiles of their
      parents' (G0) age-at-death using Cox regression. Parental social class and
      marital status were adjusted for in the analyses, as was G1's birth order and
      adult social class. For an almost entirely deceased segment of G1 (n = 1149),
      born 1915-1917, we compared exact age-at-death with G0 parents' age-at-death.
      Finally, we explored 'resilience' as a potentially important mechanism for
      intergenerational transmission of longevity, using conscript information from
      psychological interviews of G2 and G3 men. Results: G0 men's and women's ages-at
      death were independently associated with G1 midlife and old age mortality. This
      association was robust and minimally reduced when G0 and G1 social class were
      adjusted for. We observed an increased lifespan in all social groups. Median
      difference in age-at-death for sons compared to fathers was + 3.9 years, and +
      6.9 years for daughters compared to mothers.Parents' and maternal grandmother's
      longevity were associated with resilience in subsequent generations. Resilience
      scores of G2 men were also associated with those of their G3 sons and with their
      own mortality in midlife. Conclusions: The chance of reaching a high age is
      transmitted from parents to children in a modest, but robust way. Longevity
      inheritance is paralleled by the inheritance of individual resilience. Individual
      resilience, we propose, develops in the first part of life as a response to
      adversity and early experience in general. This gives rise to a transgenerational
      pathway, distinct from social class trajectories. A theory of longevity
      inheritance should bring together previous thinking around general
      susceptibility, frailty and resilience with new insights from epigenetics and
      social epidemiology.

PMID- 29349273
TI  - The contribution of three dimensions of allostatic load to racial/ethnic
      disparities in poor/fair self-rated health.
AB  - Objective: This study evaluates whether different dimensions of physiological
      dysregulation, modeled individually rather than additively mediate racial/ethnic
      disparities in self-reported health. Methods: Using data from the National Health
      and Nutrition Examination Survey (2005-2010) and the Karlson, Hold, and Breen
      (KHB) mediation model, this paper explores what operationalization of biomarker
      data most strongly mediate racial/ethnic disparities in poor/fair self-rated
      health (SRH) among adults in the United States, net of demographic,
      socioeconomic, behavioral, and medication controls. Results: Non-Hispanic blacks
      and Hispanics had significantly higher odds of reporting poor/fair self-rated
      health in comparison to non-Hispanic whites. Operationalizations of allostatic
      load that disaggregate three major dimensions of physiological dysregulation
      mediate racial/ethnic disparities strongly between non-Hispanic blacks and non
      Hispanic whites, but not between Hispanics and non-Hispanic whites.
      Disaggregating these dimensions explains racial/ethnic disparities in poor/fair
      SRH better than the continuous score. Analyses on sex-specific disparities
      indicate differences in how individual dimensions of allostatic load contribute
      to racial/ethnic disparities in poor/fair SRH differently. All individual
      dimensions are strong determinants of poor/fair SRH for males. In contrast, for
      females, the only dimension that is significantly associated with poor/fair SRH
      is inflammation. For the analytic sample, additive biomarker scores fit the data
      as well or better than other approaches, suggesting that this approach is most
      appropriate for explaining individual differences. However, in sex-specific
      analyses, the interactive approach models fit the data best for men and women.
      Conclusions: Future researchers seeking to explain racial/ethnic disparities in
      full or sex-stratified samples should consider disaggregating allostatic load by
      dimension.

PMID- 29349274
TI  - Long-run effects of early childhood exposure to cholera on final height: Evidence
      from industrializing Japan.
AB  - Pandemic cholera is one of the most topical and urgent issues in many developing
      countries. However, although a growing body of research has shown the negative
      long-run effects of infectious disease exposure on human health, the long-run
      influences of early childhood exposure to cholera have thus far been
      understudied. To bridge this gap in the body of knowledge, we draw both on new
      data describing adult height from 1899 to 1910 from comprehensive official
      Japanese army records and on data recording the regional variation in the
      intensity of cholera pandemics. By using a difference-in-differences estimation
      strategy, we find that exposure to pandemic cholera had stunting effects on the
      final height of men at that time. Our estimates also suggest that early-infancy
      exposure to cholera seems to have a stronger long-run effect on adult height than
      late-infancy exposure.

PMID- 29349275
TI  - Living with parents or grandparents increases social capital and survival: 2014
      General Social Survey-National Death Index.
AB  - Introduction: After nearly a century-long trend toward single-family living
      arrangements, people in wealthy nations are increasingly living in multi
      generational households. Multi-generational living arrangements can, in theory,
      increase psychological, social, and financial capital-factors associated with
      improvements in health and longevity. Methods: We conducted a survival analysis
      using the 2014 General Social Survey-National Death Index, a prospective multi
      year survey. We explored whether single generational living arrangements were
      associated with a higher risk of mortality than multi-generational living
      arrangements. Results: We explored this association for different groups (e.g.,
      the foreign-born and those with high self-reported stress in family
      relationships). Healthy subjects who live in two-generation households were found
      to have lower premature mortality (hazard ratio 0.9, 95% confidence interval =
      0.82, 0.99). Otherwise, we found little evidence that living arrangements matter
      for the respondents' risk of premature mortality. Conclusions: Healthy people
      living in two-generation households have longer survival than healthy people
      living on their own.

PMID- 29349276
TI  - Examining individual, interpersonal, and environmental influences on children's
      physical activity levels.
AB  - The purpose of this study was to explore individual-level socio-demographic
      factors and interpersonal-level factors related to social support, as well as the
      potential role of neighborhood and school environments that may influence the
      physical activity (PA) levels of children (ages 9-11). Child and parent
      questionnaires included individual and interpersonal factors, and PA behaviour.
      Home postal codes were used to determine the neighbourhood the child resides
      within, as well as their geographic accessibility to recreation opportunities.
      The models were assessed using a series of cross-classified random-intercept
      multi-level regression models as children's PA may be affected by both the school
      they attend and the neighbourhood in which they live. In the unadjusted model, PA
      varied significantly across school environments (gamma = 0.023; CI: 0.003-0.043),
      but not across neighbourhoods (gamma = 0.007; CI: -0.008 to 0.021). Boys were
      found to be more active compared to girls (b = 0.183; CI: 0.092-0.275), while the
      level of PA was lower for children whose fathers achieved post-secondary
      education (b = - 0.197; CI: -0.376 to 0.018) than for those whose parents
      completed only high school. The addition of the individual-level correlates did
      not have a substantial effect on level 2 variances and the level 2 variance
      associated with school environment remained statistically significant. At the
      interpersonal level, children's perception of parental support (b = 0.117; CI:
      0.091-0.143) and peer support (b = 0.111; CI: 0.079-0.142) were positively
      related to PA. The level 2 variance for the school environment became
      statistically non-significant when the interpersonal factors were added to the
      model. At the environmental level, geographic accessibility did not have a
      significant association with PA and they did not significantly affect level 1 or
      2 variance. As many children do not accrue sufficient levels of PA, identifying
      modifiable determinants is necessary to develop effective strategies to increase
      PA.

PMID- 29349277
TI  - Patterns of poverty exposure and children's trajectories of externalizing and
      internalizing behaviors.
AB  - Using data from the Child Supplement of the National Longitudinal Survey of
      Youth, we compare trajectories of externalizing and internalizing behaviors among
      children exposed to five patterns of poverty from birth to age 14: always or
      never poor - stable patterns; a single transition into or out of poverty, or
      repeated fluctuations in and out of poverty - changing patterns. We also examine
      how low maternal education and single parenthood interact with these poverty
      exposures to compound their adverse effects. Finally, we compare the magnitude of
      effects associated with the patterns of poverty exposure, as well as their
      interactions with low maternal education and single parenthood, on trajectories
      of externalizing and internalizing behaviors to determine if they are
      significantly different. Results reveal that initial levels and rates of change
      in children's trajectories of externalizing and internalizing behaviors are
      similar across the three changing patterns of poverty exposure, leading us to
      combine them into a single group representing intermittent poverty. Initial
      disparities between children who are never poor and their counterparts who are
      always or intermittently poor are constant over time for internalizing behaviors
      and grow in magnitude for externalizing behaviors. The cumulative negative effect
      of poverty exposure over time is stronger for externalizing vs. internalizing
      behaviors. Low maternal education compounds the adverse effects of persistent
      poverty, an effect that is similar for externalizing and internalizing behaviors.

PMID- 29349278
TI  - Machine learning approaches to the social determinants of health in the health
      and retirement study.
AB  - Background: Social and economic factors are important predictors of health and of
      recognized importance for health systems. However, machine learning, used
      elsewhere in the biomedical literature, has not been extensively applied to study
      relationships between society and health. We investigate how machine learning may
      add to our understanding of social determinants of health using data from the
      Health and Retirement Study. Methods: A linear regression of age and gender, and
      a parsimonious theory-based regression additionally incorporating income, wealth,
      and education, were used to predict systolic blood pressure, body mass index,
      waist circumference, and telomere length. Prediction, fit, and interpretability
      were compared across four machine learning methods: linear regression, penalized
      regressions, random forests, and neural networks. Results: All models had poor
      out-of-sample prediction. Most machine learning models performed similarly to the
      simpler models. However, neural networks greatly outperformed the three other
      methods. Neural networks also had good fit to the data (R2 between 0.4-0.6,
      versus <0.3 for all others). Across machine learning models, nine variables were
      frequently selected or highly weighted as predictors: dental visits, current
      smoking, self-rated health, serial-seven subtractions, probability of receiving
      an inheritance, probability of leaving an inheritance of at least $10,000, number
      of children ever born, African-American race, and gender. Discussion: Some of the
      machine learning methods do not improve prediction or fit beyond simpler models,
      however, neural networks performed well. The predictors identified across models
      suggest underlying social factors that are important predictors of biological
      indicators of chronic disease, and that the non-linear and interactive
      relationships between variables fundamental to the neural network approach may be
      important to consider.

PMID- 29349279
TI  - Parental population exposure to historical socioeconomic and political periods
      and grand-child's birth weight in the Lifeways Cross-Generation Cohort Study in
      the Republic of Ireland.
AB  - Exposure to deprived socioeconomic conditions during the peri-conception and
      early childhood periods can have a negative long-term impact on individuals'
      health and that of their progeny. We aimed to examine whether relatives' birth
      period affected index-child (grand-child) birthweight status in the Lifeways
      Cross-Generation Cohort in the Republic of Ireland. Participants were 943 mothers
      and offspring, 890 fathers, 938 maternal grandmothers (MGM), 700 maternal
      grandfathers (MGF) 537 paternal grandmothers (PGM) and 553 paternal grandfathers
      (PGF). Index-child's birthweight was sex-for-gestational age standardised (UK1990
      population), and then classified into low birthweight (<=10th percentile) and
      high-birthweight (>=90th percentile) and compared against normal-birthweight
      (>10th to <90th percentiles). Four adult birth periods were considered: The Free
      State (FS, 1916-1938); Emergency Act (EA, 1939-1946); Post-World War-II Baby-Boom
      (PWWII-BB, 1947-1964); and Modern Ireland (MI, 1964 onwards). Logistic regression
      was used to assess the crude and adjusted relationship between index-child's
      birthweight status and relatives' birth periods. Overall, there were 8.7% (n=82)
      index-children in the low-birthweight category, 77.9% (n=735) and 13.4% (n=126)
      within the normal and high birthweight groups respectively. Index-children whose
      mothers were born during the PWWII-BB had higher birthweight infants (Crude
      OR(COR)=1.81 (1.08-3.03) which remained the case only for male index-children
      when adjusted for co-variables (Adjusted OR(AOR)=4.61(1.71-12.42)). Parents'
      combined PWWII-BB birth period was positively associated with male index-child
      higher birthweight, even adjusted for maternal characteristics (AOR=4.60(1.69
      12.50)). MGFs born during the EA were more likely to have grandchildren with low
      birthweight after adjustment for maternal characteristics (AOR=2.45(1.03-5.85)),
      particularly for female index-children (AOR=4.74(1.16-19.25)). Both PGMs and PGFs
      born during the FS period had higher birthweight grandchildren, adjusted for
      maternal-related co-variables (PGM, AOR=3.23(1.21-8.63); PGF, AOR=3.93(1.11
      13.96)), with the effect of PGM more evident in her granddaughter (AOR=6.53(1.25
      34.04)). In conclusion, there is some evidence that period of grandparental birth
      is associated with their grandchildren's birthweights, suggesting that
      transgenerational exposures may be particular to historical context, meriting
      further exploration.

PMID- 29349280
TI  - Food insecurity and family structure in Nigeria.
AB  - The article explores a series of questions and hypotheses related to polygynous
      family structures and both household and individual-level food security outcomes,
      using the World Bank Living Standards Measurement Survey data from Nigeria,
      collected in 2011, 2013 and 2015. A Correlated Random Effects (CRE) model is used
      to examine the relationship between polygyny and household-level food security,
      and the degree to which it is mediated by household wealth, size, and livelihood.
      A Household Fixed Effect model is employed to explore whether a mother's status
      as monogamous versus polygynous relates systematically to her child's health, and
      also whether child outcomes of senior wives are better than outcomes of junior
      wives within polygynous households. At the household level, polygynous households
      are found to have better food security outcomes than monogamous households with
      differences in household composition and agricultural livelihood as potential
      explanatory mechanisms. At the individual level, however, children of polygynous
      mothers have worse nutrition outcomes than children of monogamous mothers in the
      long run. Within polygynous households, children of junior wives appear to have
      better nutritional outcomes in the long run, compared to children of more senior
      wives.

PMID- 29349281
TI  - Work disability in the United States, 1968-2015: Prevalence, duration, recovery,
      and trends.
AB  - The United States workforce is aging. At the same time more people have chronic
      conditions, for longer periods. Given these trends the importance of work
      disability, physical or nervous problems that limit a person's type or amount of
      work, is increasing. No research has examined transitions among multiple levels
      of work disability, recovery from work disability, or trends. Limited research
      has focused on work disability among African Americans and Hispanics, or
      separately for women and men. We examined these areas using data from 30,563
      adults in the 1968-2015 Panel Study of Income Dynamics. We estimated annual
      probabilities of work disability, recovery, and death with multinomial logistic
      Markov models. Microsimulations accounting for age and education estimated
      outcomes for African American, Hispanic, and non-Hispanic white women and men.
      Results from these nationally representative data suggested that the majority of
      Americans experience work disability during working life. Most spells ended with
      recovery or reduced severity. Among women, African Americans and Hispanics had
      less moderate and severe work disability than whites. Among men, African
      Americans became severely work disabled more often than whites, recovered from
      severe spells more often and had shorter severe spells, yet had more severe work
      disability at age 65. Hispanic men were more likely to report at least one spell
      of severe work disability than whites; they also had substantially more recovery
      from severe work disability, and a lower percentage of working years with work
      disability. Among African Americans and Hispanics, men were considerably more
      likely than women to have severe work disability at age 65. Work disability
      declined significantly across the study period for all groups. Although work
      disability has declined over several decades, it remains common. Results suggest
      that the majority of work disability spells end with recovery, underscoring the
      importance of rehabilitation and workplace accommodation.

PMID- 29349282
TI  - Does non-standard work mean non-standard health? Exploring links between non
      standard work schedules, health behavior, and well-being.
AB  - The last century has seen dramatic shifts in population work circumstances,
      leading to an increasing normalization of non-standard work schedules (NSWSs),
      defined as non-daytime, irregular hours. An ever-growing body of evidence links
      NSWSs to a host of non-communicable chronic conditions; yet, these associations
      primarily concentrate on the physiologic mechanisms created by circadian
      disruption and insufficient sleep. While important, not all NSWSs create such
      chronobiologic disruption, and other aspects of working time and synchronization
      could be important to the relationships between work schedules and chronic
      disease. Leveraging survey data from Project EAT, a population-based study with
      health-related behavioral and psychological data from U.S. adults aged 25-36
      years, this study explored the risks for a broad range of less healthful
      behavioral and well-being outcomes among NSWS workers compared to standard
      schedule workers (n = 1402). Variations across different NSWSs (evening,
      night/rotating, and irregular schedules) were also explored. Results indicated
      that, relative to standard schedule workers, workers with NSWSs are at increased
      risk for non-optimal sleep, substance use, greater recreational screen time,
      worse dietary practices, obesity, and depression. There was minimal evidence to
      support differences in relative risks across workers with different types of
      NSWSs. The findings provide insight into the potential links between NSWSs and
      chronic disease and indicate the relevancy social disruption and daily health
      practices may play in the production of health and well-being outcomes among
      working populations.

PMID- 29349283
TI  - Is self-rated health in adolescence a predictor of prescribed medication in
      adulthood? Findings from the Nord Trondelag Health Study and the Norwegian
      Prescription Database.
AB  - Self-rated health (SRH) is a commonly used health indicator predicting morbidity
      and mortality in a range of populations. However, the relationship between SRH
      and medication is not well established. The aim of this study was to examine
      adolescent SRH as a predictor for prescribed medication later in young adulthood.
      Eighteen years' prospective data from the Nord-Trondelag Health Study (HUNT) and
      the Norwegian Prescription Database (NorPD) were analyzed. Baseline data,
      gathered from 8982 adolescents (mean age 16.0 years) in the Young-HUNT I survey
      (1995-1997), were linked to individual data from NorPD, including information on
      all medications prescribed in 2013-2014. Gender-stratified negative binomial
      regression models were used to investigate the association between SRH and
      medication, also adjusted for age, baseline self-reported medicine use, physical
      and mental disability, smoking, and physical activity. Based on the Anatomical
      Therapeutic Chemical (ATC) Classification System, total consumption and
      consumption related to various ATC groups were examined. The adjusted analyses
      showed a dose-response relationship for females, with poorer SRH predicting
      higher average medication for both total consumption and for the ATC groups
      "Musculoskeletal system" (M), "Nervous system" (N; Analgesics (N02), Opioids
      (N02A)) and "Respiratiory system" (R). The predictive power of SRH, as well as
      the role of the adjustment factors, varies by gender and drug groups. This
      knowledge is important in order to identify risks for later disease and to
      capture pathological changes before and beyond the disease diagnosis, potentially
      preventing morbidity in the adult population.

PMID- 29349284
TI  - The relationship between physical functional limitations, and psychological
      distress: Considering a possible mediating role of pain, social support and sense
      of mastery.
AB  - The aim of this study was to examine associations between selected physical
      functional limitations related to performing daily activities and psychological
      distress. We also aimed to investigate if these associations vary across age
      (moderation), and to explore pain, sense of mastery and social support as
      potential moderators and mediators. The study was based on pooled data from two
      rounds (2008 and 2012) of a Norwegian nationally representative cross-sectional
      health survey (N = 8520) including individuals aged >= 16 years (Age groups = 16
      44 and >= 45 years). Physical functional limitations comprised decreased ability
      to: i) climb stairs, ii) carry objects, or iii) both. Psychological distress was
      measured as anxiety and depressive symptoms occurring separately or in
      combination (CAD). Of respondents reporting physical functional limitations, 8
      14% reported depressive symptoms, 5-7% anxiety symptoms, and 13-28% reported CAD.
      Physical functional limitations were significantly associated with all three
      forms of psychological distress, particularly among individuals 16-44 years, and
      were more strongly related to CAD than to anxiety or depression occurring
      separately. The association with CAD was twice as strong when both types of
      physical functional limitations were present. Pain, sense of mastery and social
      support were significant modifiers of depression, whereas all three were
      significant mediators of the relationship between physical functional limitations
      and anxiety, depression and CAD. Sense of mastery mediated the relationship
      between physical functional limitations and CAD, but most strongly among those 16
      44 years. Social support was only a significant mediator among those [Formula:
      see text] 45 years. Close associations between physical functional limitations
      and psychological distress highlight special needs among individuals experiencing
      daily functional limitations. The results also suggest that pain, low social
      support, and low sense of mastery may contribute to aggravate psychological
      distress.

PMID- 29349285
TI  - A smart-phone intervention to address mental health stigma in the construction
      industry: A two-arm randomised controlled trial.
AB  - Background: High levels of self-stigma are associated with a range of adverse
      mental health, treatment, and functional outcomes. This prospective study
      examined the effects of an electronic mental health stigma reduction intervention
      on self-stigma (self-blame, shame, and help-seeking inhibition) among male
      construction workers in Australia. Method: Male construction workers (N = 682)
      were randomly assigned to receive either the intervention condition or the wait
      list control over a six-week period. Self-stigma was assessed using the Self
      Stigma of Depression Scale at post-intervention. We conducted linear regression
      to assess the effectiveness of the intervention on self-stigma, adjusting for
      relevant covariates. Results: Self-stigma was relatively low in the sample. The
      intervention had no significant effect on self-stigma, after adjusting for
      confounders. There were reductions in stigma in both the intervention and control
      groups at 6-week follow-up. Process evaluation indicated that participants
      generally enjoyed the program and felt that it was beneficial to their mental
      health. Conclusions: These observations underscore the need for further research
      to elucidate understanding of the experience of self-stigma among employed males.

PMID- 29349286
TI  - Exercise self-efficacy in adults with congenital heart disease.
AB  - Background: Physical activity improves health, exercise tolerance and quality of
      life in adults with congenital heart disease (CHD), and exercise training is in
      most patients a high-benefit low risk intervention. However, factors that
      influence the confidence to perform exercise training, i.e. exercise self
      efficacy (ESE), in CHD patients are virtually unknown. We aimed to identify
      factors related to low ESE in adults with CHD, and potential strategies for being
      physically active. Methods: Seventy-nine adults with CHD; 38 with simple lesions
      (16 women) and 41 with complex lesions (17 women) with mean age 36.7 +/- 14.6
      years and 42 matched controls were recruited. All participants completed
      questionnaires on ESE and quality of life, carried an activity monitor
      (Actiheart) during four consecutive days and performed muscle endurance tests.
      Results: ESE in patients was categorised into low, based on the lowest quartile
      within controls, (<= 29 points, n = 34) and high (> 29 points, n = 45). Patients
      with low ESE were older (42.9 +/- 15.1 vs. 32.0 +/- 12.4 years, p = 0.001), had
      more complex lesions (65% vs. 42%, p = 0.05) more often had New York Heart
      Association functional class III (24% vs. 4%, p = 0.01) and performed fewer
      shoulder flexions (32.5 +/- 15.5 vs. 47.7 +/- 25.0, p = 0.001) compared with
      those with high ESE. In a logistic multivariate model age (OR; 1.06, 95% CI 1.02
      1.10), and number of shoulder flexions (OR; 0.96, 95% CI 0.93-0.99) were
      associated with ESE. Conclusion: In this study we show that many adults with CHD
      have low ESE. Age is an important predictor of low ESE and should, therefore, be
      considered in counselling patients with CHD. In addition, muscle endurance
      training may improve ESE, and thus enhance the potential for being physically
      active in this population.

PMID- 29349287
TI  - Barriers to Diet and Exercise among Nepalese Type 2 Diabetic Patients.
AB  - This study aims to identify the modifiable barriers encountered by type 2
      diabetic patients in Nepal to achieving their recommended dietary and exercise
      advice. A cross-sectional study was conducted among 197 type 2 diabetic patients,
      attending a diabetic clinic. Binary logistic regression models were used to
      identify perceived barriers. About 41% and 46% of the participants were
      noncompliant to diet and exercise advice, respectively; only 35.5% the
      participants were compliant to both. Perceived social acceptability (OR = 0.14;
      95% CI: 0.03-0.58) and reminder to action (OR = 2.77; 95% CI: 1.38-5.53) were
      associated with noncompliance to diet. Most of the barriers to diet were related
      to taste, feast and festivals, lack of knowledge, and availability of healthy
      options. Self-efficacy (OR = 0.09; 95% CI: 0.02-0.34) and social acceptability
      (OR = 0.12; 95% CI: 0.04-0.34) were significant predictors of noncompliance to
      exercise. The supportive role of children and spouse and the opposing role of
      friends and relatives were important for compliance to both. A misconception on
      diabetes severity, effectiveness of healthy lifestyle, and exercise timing was
      prevalent among the study participants. Addressing the modifiable barriers
      identified in this study is essential for successful diabetes management in
      Nepal.

PMID- 29349288
TI  - The In Vivo Dynamics of HIV Infection with the Influence of Cytotoxic T
      Lymphocyte Cells.
AB  - The in vivo dynamics of HIV infection, the infection mechanism, the cell types
      infected, and the role played by the cytotoxic cells are poorly understood. This
      paper uses mathematical modelling as a tool to investigate and analyze the immune
      system dynamics in the presence of HIV infection. We formulate a six-dimensional
      model of nonlinear ordinary differential equations derived from known biological
      interaction mechanisms between the immune cells and the HIV virions. The
      existence and uniqueness as well as positivity and boundedness of the solutions
      to the differential equations are proved. Furthermore, the disease-free
      reproduction number is derived and the local asymptotic stability of the model
      investigated. In addition, numerical analysis is carried out to illustrate the
      importance of having R0 < 1. Lastly, the biological dynamics of HIV in vivo
      infection are graphically represented. The results indicate that, at acute
      infection, the cytotoxic T-cells play a paramount role in reducing HIV viral
      replication. In addition, the results emphasize the importance of developing
      controls, interventions, and management policies that when implemented would lead
      to viral suppression during acute infection.

PMID- 29349289
TI  - Mixed Neurodevelopmental and Neurodegenerative Pathology in Nhe6-Null Mouse Model
      of Christianson Syndrome.
AB  - Christianson syndrome (CS) is an X-linked disorder resulting from loss-of
      function mutations in SLC9A6, which encodes the endosomal Na+/H+ exchanger 6
      (NHE6). Symptoms include early developmental delay, seizures, intellectual
      disability, nonverbal status, autistic features, postnatal microcephaly, and
      progressive ataxia. Neuronal development is impaired in CS, involving defects in
      neuronal arborization and synaptogenesis, likely underlying diminished brain
      growth postnatally. In addition to neurodevelopmental defects, some reports have
      supported neurodegenerative pathology in CS with age. The objective of this study
      was to determine the nature of progressive changes in the postnatal brain in Nhe6
      null mice. We examined the trajectories of brain growth and atrophy in mutant
      mice from birth until very old age (2 yr). We report trajectories of volume
      changes in the mutant that likely reflect both brain undergrowth as well as
      tissue loss. Reductions in volume are first apparent at 2 mo, particularly in the
      cerebellum, which demonstrates progressive loss of Purkinje cells (PCs). We
      report PC loss in two distinct Nhe6-null mouse models. More widespread reductions
      in tissue volumes, namely, in the hippocampus, striatum, and cortex, become
      apparent after 2 mo, largely reflecting delays in growth with more limited tissue
      losses with aging. Also, we identify pronounced glial responses, particularly in
      major fiber tracts such as the corpus callosum, where the density of activated
      astrocytes and microglia are substantially increased. The prominence of the glial
      response in axonal tracts suggests a primary axonopathy. Importantly, therefore,
      our data support both neurodevelopmental and degenerative mechanisms in the
      pathobiology of CS.

PMID- 29349290
TI  - A Novel Neuroprotective Mechanism for Lithium That Prevents Association of the
      p75NTR-Sortilin Receptor Complex and Attenuates proNGF-Induced Neuronal Death In
      Vitro and In Vivo.
AB  - Neurotrophins play critical roles in the survival, maintenance and death of
      neurons. In particular, proneurotrophins have been shown to mediate cell death
      following brain injury induced by status epilepticus (SE) in rats. Previous
      studies have shown that pilocarpine-induced seizures lead to increased levels of
      proNGF, which binds to the p75NTR-sortilin receptor complex to elicit apoptosis.
      A screen to identify compounds that block proNGF binding and uptake into cells
      expressing p75 and sortilin identified lithium citrate as a potential inhibitor
      of proNGF and p75NTR-mediated cell death. In this study, we demonstrate that low,
      submicromolar doses of lithium citrate effectively inhibited proNGF-induced cell
      death in cultured neurons and protected hippocampal neurons following pilocarpine
      induced SE in vivo. We analyzed specific mechanisms by which lithium citrate
      afforded neuroprotection and determined that lithium citrate prevented the
      association and internalization of the p75NTR-sortilin receptor complex. Our
      results demonstrate a novel mechanism by which low-dose treatments of lithium
      citrate are effective in attenuating p75NTR-mediated cell death in vitro and in
      vivo.

PMID- 29349291
TI  - Spontaneous Infraslow Fluctuations Modulate Hippocampal EPSP-PS Coupling.
AB  - Extensive trial-to-trial variability is a hallmark of most behavioral, cognitive,
      and physiological processes. Spontaneous brain activity (SBA), a ubiquitous
      phenomenon that coordinates levels and patterns of neuronal activity throughout
      the brain, may contribute to this variability by dynamically altering neuronal
      excitability. In freely-behaving male rats, we observed extensive variability of
      the hippocampal evoked response across 28-min recording periods despite
      maintaining constant stimulation parameters of the medial perforant path. This
      variability was related to antecedent SBA: increases in low-frequency (0.5-9 Hz)
      and high-frequency (40.25-100 Hz) band-limited power (BLP) in the 4-s preceding
      stimulation were associated with decreased slope of the field EPSP (fEPSP) and
      increased population spike (PS) amplitude. These fluctuations in SBA and evoked
      response magnitude did not appear stochastic but rather exhibited coordinated
      activity across infraslow timescales (0.005-0.02 Hz). Specifically, infraslow
      fluctuations in high- and low-frequency BLP were antiphase with changes in fEPSP
      slope and in phase with changes in PS amplitude. With these divergent effects on
      the fEPSP and PS, infraslow SBA ultimately modulates EPSP-PS coupling and thereby
      enables hippocampal circuitry to generate heterogeneous outputs from identical
      inputs. Consequently, infraslow SBA appears well suited to dynamically alter
      sensory selection and information processing and highlights the fundamental role
      of endogenous neuronal activity for shaping the brain's response to incoming
      stimuli.

PMID- 29349292
TI  - Membrane insertion of-and membrane potential sensing by-semiconductor voltage
      nanosensors: Feasibility demonstration.
AB  - We developed membrane voltage nanosensors that are based on inorganic
      semiconductor nanoparticles. We provide here a feasibility study for their
      utilization. We use a rationally designed peptide to functionalize the
      nanosensors, imparting them with the ability to self-insert into a lipid membrane
      with a desired orientation. Once inserted, these nanosensors could sense membrane
      potential via the quantum confined Stark effect, with a single-particle
      sensitivity. With further improvements, these nanosensors could potentially be
      used for simultaneous recording of action potentials from multiple neurons in a
      large field of view over a long duration and for recording electrical signals on
      the nanoscale, such as across one synapse.

PMID- 29349293
TI  - Experimenter gender and replicability in science.
AB  - There is a replication crisis spreading through the annals of scientific inquiry.
      Although some work has been carried out to uncover the roots of this issue, much
      remains unanswered. With this in mind, this paper investigates how the gender of
      the experimenter may affect experimental findings. Clinical trials are regularly
      carried out without any report of the experimenter's gender and with dubious
      knowledge of its influence. Consequently, significant biases caused by the
      experimenter's gender may lead researchers to conclude that therapeutics or other
      interventions are either overtreating or undertreating a variety of conditions.
      Bearing this in mind, this policy paper emphasizes the importance of reporting
      and controlling for experimenter gender in future research. As backdrop, it
      explores what we know about the role of experimenter gender in influencing
      laboratory results, suggests possible mechanisms, and suggests future areas of
      inquiry.

PMID- 29349294
TI  - Changes in seasonal snow water equivalent distribution in High Mountain Asia
      (1987 to 2009).
AB  - Snow meltwaters account for most of the yearly water budgets of many catchments
      in High Mountain Asia (HMA). We examine trends in snow water equivalent (SWE)
      using passive microwave data (1987 to 2009). We find an overall decrease in SWE
      in HMA, despite regions of increased SWE in the Pamir, Kunlun Shan, Eastern
      Himalaya, and Eastern Tien Shan. Although the average decline in annual SWE
      across HMA (contributing area, 2641 * 103 km2) is low (average, -0.3%), annual
      SWE losses conceal distinct seasonal and spatial heterogeneities across the study
      region. For example, the Tien Shan has seen both strong increases in winter SWE
      and sharp declines in spring and summer SWE. In the majority of catchments, the
      most negative SWE trends are found in mid-elevation zones, which often correspond
      to the regions of highest snow-water storage and are somewhat distinct from
      glaciated areas. Negative changes in SWE storage in these mid-elevation zones
      have strong implications for downstream water availability.

PMID- 29349295
TI  - A Triassic-Jurassic window into the evolution of Lepidoptera.
AB  - On the basis of an assemblage of fossilized wing scales recovered from latest
      Triassic and earliest Jurassic sediments from northern Germany, we provide the
      earliest evidence for Lepidoptera (moths and butterflies). The diverse scales
      confirm a (Late) Triassic radiation of lepidopteran lineages, including the
      divergence of the Glossata, the clade that comprises the vast multitude of extant
      moths and butterflies that have a sucking proboscis. The microfossils extend the
      minimum calibrated age of glossatan moths by ca. 70 million years, refuting
      ancestral association of the group with flowering plants. Development of the
      proboscis may be regarded as an adaptive innovation to sucking free liquids for
      maintaining the insect's water balance under arid conditions. Pollination drops
      secreted by a variety of Mesozoic gymnosperms may have been non-mutualistically
      exploited as a high-energy liquid source. The early evolution of the Lepidoptera
      was probably not severely interrupted by the end-Triassic biotic crisis.

PMID- 29349296
TI  - Unlocking data sets by calibrating populations of models to data density: A study
      in atrial electrophysiology.
AB  - The understanding of complex physical or biological systems nearly always
      requires a characterization of the variability that underpins these processes. In
      addition, the data used to calibrate these models may also often exhibit
      considerable variability. A recent approach to deal with these issues has been to
      calibrate populations of models (POMs), multiple copies of a single mathematical
      model but with different parameter values, in response to experimental data. To
      date, this calibration has been largely limited to selecting models that produce
      outputs that fall within the ranges of the data set, ignoring any trends that
      might be present in the data. We present here a novel and general methodology for
      calibrating POMs to the distributions of a set of measured values in a data set.
      We demonstrate our technique using a data set from a cardiac electrophysiology
      study based on the differences in atrial action potential readings between
      patients exhibiting sinus rhythm (SR) or chronic atrial fibrillation (cAF) and
      the Courtemanche-Ramirez-Nattel model for human atrial action potentials. Not
      only does our approach accurately capture the variability inherent in the
      experimental population, but we also demonstrate how the POMs that it produces
      may be used to extract additional information from the data used for calibration,
      including improved identification of the differences underlying stratified data.
      We also show how our approach allows different hypotheses regarding the
      variability in complex systems to be quantitatively compared.

PMID- 29349297
TI  - Organic matter in extraterrestrial water-bearing salt crystals.
AB  - Direct evidence of complex prebiotic chemistry from a water-rich world in the
      outer solar system is provided by the 4.5-billion-year-old halite crystals hosted
      in the Zag and Monahans (1998) meteorites. This study offers the first
      comprehensive organic analysis of the soluble and insoluble organic compounds
      found in the millimeter-sized halite crystals containing brine inclusions and
      sheds light on the nature and activity of aqueous fluids on a primitive parent
      body. Associated with these trapped brines are organic compounds exhibiting wide
      chemical variations representing organic precursors, intermediates, and reaction
      products that make up life's precursor molecules such as amino acids. The organic
      compounds also contain a mixture of C-, O-, and N-bearing macromolecular carbon
      materials exhibiting a wide range of structural order, as well as aromatic,
      ketone, imine, and/or imidazole compounds. The enrichment in 15N is comparable to
      the organic matter in pristine Renazzo-type carbonaceous chondrites, which
      reflects the sources of interstellar 15N, such as ammonia and amino acids. The
      amino acid content of the Zag halite deviates from the meteorite matrix,
      supporting an exogenic origin of the halite, and therefore, the Zag meteorite
      contains organics synthesized on two distinct parent bodies. Our study suggests
      that the asteroidal parent body where the halite precipitated, potentially
      asteroid 1 Ceres, shows evidence for a complex combination of biologically and
      prebiologically relevant molecules.

PMID- 29349298
TI  - Direct measurements of DOCO isomers in the kinetics of OD + CO.
AB  - Quantitative and mechanistically detailed kinetics of the reaction of hydroxyl
      radical (OH) with carbon monoxide (CO) have been a longstanding goal of
      contemporary chemical kinetics. This fundamental prototype reaction plays an
      important role in atmospheric and combustion chemistry, motivating studies for
      accurate determination of the reaction rate coefficient and its pressure and
      temperature dependence at thermal reaction conditions. This intricate dependence
      can be traced directly to details of the underlying dynamics (formation,
      isomerization, and dissociation) involving the reactive intermediates cis- and
      trans-HOCO, which can only be observed transiently. Using time-resolved frequency
      comb spectroscopy, comprehensive mechanistic elucidation of the kinetics of the
      isotopic analog deuteroxyl radical (OD) with CO has been realized. By monitoring
      the concentrations of reactants, intermediates, and products in real time, the
      branching and isomerization kinetics and absolute yields of all species in the OD
      + CO reaction are quantified as a function of pressure and collision partner.

PMID- 29349299
TI  - Limited contribution of ancient methane to surface waters of the U.S. Beaufort
      Sea shelf.
AB  - In response to warming climate, methane can be released to Arctic Ocean sediment
      and waters from thawing subsea permafrost and decomposing methane hydrates.
      However, it is unknown whether methane derived from this sediment storehouse of
      frozen ancient carbon reaches the atmosphere. We quantified the fraction of
      methane derived from ancient sources in shelf waters of the U.S. Beaufort Sea, a
      region that has both permafrost and methane hydrates and is experiencing
      significant warming. Although the radiocarbon-methane analyses indicate that
      ancient carbon is being mobilized and emitted as methane into shelf bottom
      waters, surprisingly, we find that methane in surface waters is principally
      derived from modern-aged carbon. We report that at and beyond approximately the
      30-m isobath, ancient sources that dominate in deep waters contribute, at most,
      10 +/- 3% of the surface water methane. These results suggest that even if there
      is a heightened liberation of ancient carbon-sourced methane as climate change
      proceeds, oceanic oxidation and dispersion processes can strongly limit its
      emission to the atmosphere.

PMID- 29349300
TI  - Tensile forces drive a reversible fibroblast-to-myofibroblast transition during
      tissue growth in engineered clefts.
AB  - Myofibroblasts orchestrate wound healing processes, and if they remain activated,
      they drive disease progression such as fibrosis and cancer. Besides growth factor
      signaling, the local extracellular matrix (ECM) and its mechanical properties are
      central regulators of these processes. It remains unknown whether transforming
      growth factor-beta (TGF-beta) and tensile forces work synergistically in up
      regulating the transition of fibroblasts into myofibroblasts and whether
      myofibroblasts undergo apoptosis or become deactivated by other means once tissue
      homeostasis is reached. We used three-dimensional microtissues grown in vitro
      from fibroblasts in macroscopically engineered clefts for several weeks and found
      that fibroblasts transitioned into myofibroblasts at the highly tensed growth
      front as the microtissue progressively closed the cleft, in analogy to closing a
      wound site. Proliferation was up-regulated at the growth front, and new highly
      stretched fibronectin fibers were deposited, as revealed by fibronectin
      fluorescence resonance energy transfer probes. As the tissue was growing, the ECM
      underneath matured into a collagen-rich tissue containing mostly fibroblasts
      instead of myofibroblasts, and the fibronectin fibers were under reduced tension.
      This correlated with a progressive rounding of cells from the growth front
      inward, with decreased alpha-smooth muscle actin expression, YAP nuclear
      translocation, and cell proliferation. Together, this suggests that the
      myofibroblast phenotype is stabilized at the growth front by tensile forces, even
      in the absence of endogenously supplemented TGF-beta, and reverts into a
      quiescent fibroblast phenotype already 10 MUm behind the growth front, thus
      giving rise to a myofibroblast-to-fibroblast transition. This is the hallmark of
      reaching prohealing homeostasis.

PMID- 29349301
TI  - Emergence of Kondo lattice behavior in a van der Waals itinerant ferromagnet,
      Fe3GeTe2.
AB  - Searching for heavy fermion (HF) states in non-f-electron systems becomes an
      interesting issue, especially in the presence of magnetism, and can help explain
      the physics of complex compounds. Using angle-resolved photoemission
      spectroscopy, scanning tunneling microscopy, physical properties measurements,
      and the first-principles calculations, we observe the HF state in a 3d-electron
      van der Waals ferromagnet, Fe3GeTe2. Upon entering the ferromagnetic state, a
      massive spectral weight transfer occurs, which results from the exchange
      splitting. Meanwhile, the Fermi surface volume and effective electron mass are
      both enhanced. When the temperature drops below a characteristic temperature T*,
      heavy electrons gradually emerge with further enhanced effective electron mass.
      The coexistence of ferromagnetism and HF state can be well interpreted by the
      dual properties (itinerant and localized) of 3d electrons. This work expands the
      limit of ferromagnetic HF materials from f- to d-electron systems and illustrates
      the positive correlation between ferromagnetism and HF state in the 3d-electron
      material, which is quite different from the f-electron systems.

PMID- 29349302
TI  - Fast, noise-free memory for photon synchronization at room temperature.
AB  - Future quantum photonic networks require coherent optical memories for
      synchronizing quantum sources and gates of probabilistic nature. We demonstrate a
      fast ladder memory (FLAME) mapping the optical field onto the superposition
      between electronic orbitals of rubidium vapor. Using a ladder-level system of
      orbital transitions with nearly degenerate frequencies simultaneously enables
      high bandwidth, low noise, and long memory lifetime. We store and retrieve 1.7-ns
      long pulses, containing 0.5 photons on average, and observe short-time external
      efficiency of 25%, memory lifetime (1/e) of 86 ns, and below 10-4 added noise
      photons. Consequently, coupling this memory to a probabilistic source would
      enhance the on-demand photon generation probability by a factor of 12, the
      highest number yet reported for a noise-free, room temperature memory. This paves
      the way toward the controlled production of large quantum states of light from
      probabilistic photon sources.

PMID- 29349303
TI  - Integrated Medical Curriculum: Advantages and Disadvantages.
AB  - Most curricula for medical education have been integrated horizontally and
      vertically--vertically between basic and clinical sciences. The Flexnerian
      curriculum has disappeared to permit integration between basic sciences and
      clinical sciences, which are taught throughout the curriculum. We have proposed a
      different form of integration where the horizontal axis represents the defined
      learning outcomes and the vertical axis represents the teaching of the sciences
      throughout the courses. We believe that a mere integration of basic and clinical
      sciences is not enough because it is necessary to emphasize the importance of
      humanism as well as health population sciences in medicine. It is necessary to
      integrate basic and clinical sciences, humanism, and health population in the
      vertical axis, not only in the early years but also throughout the curriculum,
      presupposing the use of active teaching methods based on problems or cases in
      small groups.

PMID- 29349304
TI  - Negative Marking and the Student Physician--A Descriptive Study of Nigerian
      Medical Schools.
AB  - Background: There is considerable debate about the two most commonly used scoring
      methods, namely, the formula scoring (popularly referred to as negative marking
      method in our environment) and number right scoring methods. Although the
      negative marking scoring system attempts to discourage students from guessing in
      order to increase test reliability and validity, there is the view that it is an
      excessive and unfair penalty that also increases anxiety. Feedback from students
      is part of the education process; thus, this study assessed the perception of
      medical students about negative marking method for multiple choice question (MCQ)
      examination formats and also the effect of gender and risk-taking behavior on
      scores obtained with this assessment method. Methods: This was a prospective
      multicenter survey carried out among fifth year medical students in Enugu State
      University and the University of Nigeria. A structured questionnaire was
      administered to 175 medical students from the two schools, while a class test was
      administered to medical students from Enugu State University. Qualitative
      statistical methods including frequencies, percentages, and chi square were used
      to analyze categorical variables. Quantitative statistics using analysis of
      variance was used to analyze continuous variables. Results: Inquiry into
      assessment format revealed that most of the respondents preferred MCQs (65.9%).
      One hundred and thirty students (74.3%) had an unfavorable perception of negative
      marking. Thirty-nine students (22.3%) agreed that negative marking reduces the
      tendency to guess and increases the validity of MCQs examination format in
      testing knowledge content of a subject compared to 108 (61.3%) who disagreed with
      this assertion (chi2 = 23.0, df = 1, P = 0.000). The median score of the students
      who were not graded with negative marking was significantly higher than the score
      of the students graded with negative marking (P = 0.001). There was no
      statistically significant difference in the risk-taking behavior between male and
      female students in their MCQ answering patterns with negative marking method (P =
      0.618). Conclusions: In the assessment of students, it is more desirable to adopt
      fair penalties for discouraging guessing rather than excessive penalties for
      incorrect answers, which could intimidate students in negative marking schemes.
      There is no consensus on the penalty for an incorrect answer. Thus, there is a
      need for continued research into an effective and objective assessment tool that
      will ensure that the students' final score in a test truly represents their level
      of knowledge.

PMID- 29349305
TI  - From Introduction to Integration: Providing Community-Engaged Structure for
      Interprofessional Education.
AB  - Background: Training future healthcare profession students using
      interprofessional education (IPE) is critical to improve quality of health care
      and patient safety. Objective: The objective of this study was to implement an
      IPE program and determine student satisfaction with each session, including a
      clinical case requiring teams with members from each profession addressing
      clinical scenarios. Subjects: The subjects of this study were students from
      Athletic Training, Medicine, Nursing, Pharmacy, Physical Therapy, Physician
      Assistant, Social Work, and Speech-Language Pathology. Methods: Evaluations,
      administered to all participating students, consisted of Likert-style responses,
      rating agreement with a series of questions, and space for descriptive comments.
      Score differences for each question were compared using independent group t-tests
      with a P-value of 0.05 to determine statistical significance. Results: There were
      statistically higher satisfaction ratings for the problem-based learning case
      when compared to less interactive sessions (P < 0.0001). Conclusion: Students
      perceived benefits of the IPE program. Perceptions improved when various students
      had the opportunity to work together on clinically relevant problems.

PMID- 29349307
TI  - Blended Learning in Obstetrics and Gynecology Resident Education: Impact on
      Resident Clinical Performance.
AB  - Problem: Effects of residents' blended learning on their clinical performance
      have rarely been reported. A blended learning pilot program was instituted at
      Southern Illinois University School of Medicine's Obstetrics and Gynecology
      program. One of the modules was chronic hypertension in pregnancy. We sought to
      evaluate if the resident blended learning was transferred to their clinical
      performance six months after the module. Intervention: A review of patient charts
      demonstrated inadequate documentation of history, evaluation, and counseling of
      patients with chronic hypertension at the first prenatal visit by Obstetrics and
      Gynecology (OB/GYN) residents. A blended learning module on chronic hypertension
      in pregnancy was then provided to the residents. A retrospective chart review was
      then performed to assess behavioral changes in the OB/GYN residents. Context:
      This intervention was carried out at the Department of Obstetrics and Gynecology,
      Southern Illinois University. All 16 OB/GYN residents were enrolled in this
      module as part of their educational curriculum. A query of all prenatal patients
      diagnosed with chronic hypertension presenting to the OB/GYN resident clinics
      four months prior to the implementation of the blended learning module (March
      2015-June 2015) and six months after (July 20, 2015-February 2016) was performed.
      Data were collected from outpatient charts utilizing the electronic medical
      record. Data were abstracted from resident documentation at the first prenatal
      visit. Outcome: The residents thought that the blended learning module was
      applicable to performance improvement in the real-world setting. Patients
      evaluated before (n = 10) and after (n = 7) the intervention were compared. After
      the intervention, there was an increase in assessment of baseline liver enzymes,
      referral for electrocardiogram, and early assessment for diabetes in the obese
      patients. More patients were provided a blood pressure cuff after the module
      (71.4% vs. 20%). Data were provided to the residents in an informal setting.
      Discussion during this session suggested that inconsistent use of the algorithm
      and incomplete documentation were reasons for the findings. Lessons Learned: This
      study suggests that blended learning may be a viable tool to support sustained
      changes in the performance of OB/GYN residents. Scheduled follow-up should be
      employed to facilitate and ensure continued learning and behavioral changes.

PMID- 29349306
TI  - Case-Based Learning and its Application in Medical and Health-Care Fields: A
      Review of Worldwide Literature.
AB  - Introduction: Case-based learning (CBL) is a newer modality of teaching
      healthcare. In order to evaluate how CBL is currently used, a literature search
      and review was completed. Methods: A literature search was completed using an
      OVID(c) database using PubMed as the data source, 1946-8/1/2015. Key words used
      were "Case-based learning" and "medical education", and 360 articles were
      retrieved. Of these, 70 articles were selected to review for location, human
      health care related fields of study, number of students, topics, delivery
      methods, and student level. Results: All major continents had studies on CBL.
      Education levels were 64% undergraduate and 34% graduate. Medicine was the most
      frequently represented field, with articles on nursing, occupational therapy,
      allied health, child development and dentistry. Mean number of students per study
      was 214 (7-3105). The top 3 most common methods of delivery were live
      presentation in 49%, followed by computer or web-based in 20% followed by mixed
      modalities in 19%. The top 3 outcome evaluations were: survey of participants,
      knowledge test, and test plus survey, with practice outcomes less frequent.
      Selected studies were reviewed in greater detail, highlighting advantages and
      disadvantages of CBL, comparisons to Problem-based learning, variety of fields in
      healthcare, variety in student experience, curriculum implementation, and finally
      impact on patient care. Conclusions: CBL is a teaching tool used in a variety of
      medical fields using human cases to impart relevance and aid in connecting theory
      to practice. The impact of CBL can reach from simple knowledge gains to changing
      patient care outcomes.

PMID- 29349308
TI  - Creating a Novel Cardiac Limited Ultrasound Exam Curriculum for Internal Medical
      Residency: Four Unanticipated Tasks.
AB  - Over the past two decades, our internal medicine residency has created a unique
      postgraduate education in internal medicine by incorporating a formal curriculum
      in point-of-care cardiac ultrasound as a mandatory component. The details
      regarding content and implementation were critical to the initial and subsequent
      success of this novel program. In this paper, we discuss the evidence-based
      advances, considerations, and pitfalls that we have encountered in the program's
      development through the discussion of four unanticipated tasks unique to a point
      of-care ultrasound curriculum. The formatted discussion of these tasks will
      hopefully assist development of ultrasound programs at other institutions.

PMID- 29349309
TI  - Group Learning Assessments as a Vital Consideration in the Implementation of New
      Peer Learning Pedagogies in the Basic Science Curriculum of Health Profession
      Programs.
AB  - Inspired by reports of successful outcomes in health profession education
      literature, peer learning has progressively grown to become a fundamental
      characteristic of health profession curricula. Many studies, however, are
      anecdotal or philosophical in nature, particularly when addressing the
      effectiveness of assessments in the context of peer learning. This commentary
      provides an overview of the rationale for using group assessments in the basic
      sciences curriculum of health profession programs and highlights the challenges
      associated with implementing group assessments in this context. The dearth of
      appropriate means for measuring group process suggests that professional
      collaboration competencies need to be more clearly defined. Peer learning
      educators are advised to enhance their understanding of social psychological
      research in order to implement best practices in the development of appropriate
      group assessments for peer learning.

PMID- 29349310
TI  - Integration of Dermatology-Focused Physical Diagnosis Rounds and Case-Based
      Learning within the Internal Medicine Medical Student Clerkship.
AB  - Background: Over half of dermatologic conditions are seen by nondermatologists,
      yet medical students receive little dermatology education. Medical students in
      the clinical years of training at our institution felt insecure in their physical
      diagnosis skills for dermatologic conditions. Objective: The objective of this
      study was to implement dermatology-focused curricula within the Internal Medicine
      (IM) Core Clerkship to increase student confidence in diagnosing skin diseases.
      Methods: Two dermatology-focused sessions were integrated into the IM Clerkship.
      A faculty dermatologist leads students on a dermatology-focused physical
      diagnosis "Skin Rounds", where patients are seen at the bedside and students
      practice describing skin lesions and forming a differential diagnosis. Students
      also participate in a case-based active learning session. A dermatologist selects
      images of common skin conditions that students describe utilizing appropriate
      terminology and offer a differential diagnosis. The impact of these sessions was
      assessed through survey-based student feedback and by comparing the results from
      the IM Shelf Exam before and after intervention. Results: A total of 74 students
      completed the skin rounds survey (32% response rate). About 99% (n = 73) of
      students felt that skin rounds were effective and useful, and 92% (n = 68) of
      students reported that they felt more confident in describing skin lesions
      afterward. A total of 43 students completed the case-based learning session
      survey (37% response rate), and 98% (n = 42) of students strongly agreed or
      agreed that the session was effective and useful. Performance on the dermatologic
      questions of the IM Shelf Exam was analyzed. While not statistically significant
      at P < 0.05, students improved from an average of 77% correct responses before
      intervention to 79% afterward (P = 0.60). Conclusions: Our case-based and bedside
      teaching interventions were met with high satisfaction from medical students and
      increased their confidence in describing skin lesions. This intervention can
      serve as a model to improve dermatology education and can be adapted to utilize
      the IM clerkship to address curriculum inadequacies at other institutions.

PMID- 29349311
TI  - Capturing the Integration of Practice-Based Learning with Beliefs, Values, and
      Attitudes using Modified Concept Mapping.
AB  - Practice-based learning integrates the cognitive, psychomotor, and affective
      domains and is influenced by students' beliefs, values, and attitudes. Concept
      mapping has been shown to effectively demonstrate students' changing concepts and
      knowledge structures. This article discusses how concept mapping was modified to
      capture students' perceptions of the connections between the domains of thinking
      and knowing, emotions, behavior, attitudes, values, and beliefs and the specific
      experiences related to these, over a period of eight months of practice-based
      clinical learning. The findings demonstrate that while some limitations exist,
      modified concept mapping is a manageable way to gather rich data about students'
      perceptions of their clinical practice experiences. These findings also highlight
      the strong integrating influence of beliefs and values on other areas of
      practice, suggesting that these need to be attended to as part of a student's
      educational program.

PMID- 29349312
TI  - Combining Expertise: Reflecting on a Team Approach to Curriculum Development and
      Implementation.
AB  - Introduction: This article discussed curriculum development and implementation
      using a unique collaboration of basic scientists and clinicians functioning as
      course co-directors. It explores the pros, cons, and unintended consequences of
      this integrated approach through reflections of the faculty involved. Methods:
      Ten faculty participated in semi-structured phone interviews to reflect on their
      experiences. Results: Analysis of interview transcripts revealed four key themes:
      (1) the value of the basic scientist and clinician partnership, (2) strategies
      for coordination, (3) balancing responsibilities, and (4) hierarchy and power.
      Discussion: This study identified that both basic scientists and clinicians
      experienced benefits from using a course co-director collaborative approach to
      curriculum development and implementation. While challenges are also noted, the
      benefits of the collaboration were evident in course organization, course
      evaluation reports, student feedback, and USMLE Step I pass rate.

PMID- 29349313
TI  - Prepared for Practice? Interns' Experiences of Undergraduate Clinical Skills
      Training in Ireland.
AB  - Background: Many previous studies on internship have reported a lack of
      preparedness for the role. More recently in Ireland, medical schools have
      introduced formal clinical skills training programmes. This study sought to
      evaluate the impact, if any, of formal skills training in the medical training on
      intern's preparedness for practice. Methods: The study utilized a survey approach
      followed by focus group discussions. The aim was to identify the skills that were
      taught and assessed in medical training and the skills that were actually
      required in their intern year. Results: Most interns had received skills training
      in designated skills laboratories. No intern had received training in all skills
      advised in the European guidelines. Skills taught to all interns were intravenous
      cannulation, basic life support, and basic suture. Skills required from all
      interns were intravenous cannulation, phlebotomy, and arterial blood sampling.
      Removal of peripherally inserted central line (PICC) lines, central lines, and
      chest drains were commonly requested but not taught. Senior staff underestimated
      skill abilities and expected failure. Conclusion: These findings identify
      discordance between the skills taught and the skills required in the job. There
      is a need for standardization in the clinical skills training to ensure that all
      interns enter practice with equal competencies. Consideration should be given to
      experiential learning opportunities such as subintern programmes to consolidate
      learning and improve preparedness. Improvement in communications with senior
      clinicians is indicated to ensure that expectations are realistic and reflective
      of actual training.

PMID- 29349314
TI  - How Effective is a Dental Workshop at Improving the Knowledge and Confidence of
      Medical Students in the Management of Dental Emergencies?
AB  - The purpose of this study was to evaluate the effect of a three-hour hands-on
      workshop for medical students and residents on their pre- and postcourse
      knowledge and confidence in managing dental emergencies. A 1-hour lecture
      followed by four 20-minute "hands-on" skill stations on dental mannequins was
      administered to a group of 30 medical students and residents. Pre- and
      postworkshop questionnaire surveys were conducted. There was a significant
      increase in the percent of attendees who responded correctly to three of the four
      knowledge questions following the workshop (P-value < 0.005). Confidence, as
      expressed in various statements, about treating dental emergencies was
      significantly improved after the lecture for eight of the nine statements. These
      findings indicate that dental knowledge is generally not provided during medical
      training. Our interactive workshop appeared to be effective in increasing this
      knowledge and self-reported confidence in handling dental emergencies. These
      findings clearly indicate the need for additional dental education during medical
      school. The use of a hands-on workshop may be one model for achieving this goal.

PMID- 29349315
TI  - Assessing the Development of Medical Students' Personal and Professional Skills
      by Portfolio.
AB  - The introduction of a new domain of learning for Personal and Professional Skills
      in the medical program at the University of Auckland in New Zealand has involved
      the compilation of a portfolio for assessment. This departure from the
      traditional assessment methods predominantly used in the past has been
      challenging to design, introduce, and maintain as a relevant and authentic
      assessment method. We present the portfolio format along with the process for its
      introduction and appraise the challenges, strengths, and limitations of the
      approach within the context of the current literature. We then outline a cyclical
      model of evaluation used to monitor and fine-tune the portfolio tasks and
      implementation process, in response to student and assessor feedback. The
      portfolios have illustrated the level of insight, maturity, and synthesis of
      personal and professional qualities that students are capable of achieving. The
      Auckland medical program strives to foster these qualities in its students, and
      the portfolio provides an opportunity for students to demonstrate their
      reflective abilities. Moreover, the creation of a Personal and Professional
      Skills domain with the portfolio as its key assessment emphasizes the importance
      of reflective practice and personal and professional development and gives a
      clear message that these are fundamental longitudinal elements of the program.

PMID- 29349316
TI  - White Coat Ceremony as a Professional Identity Formation Activity in a United
      States Family Medicine Residency Program.
AB  - Introduction: White coat ceremonies (WCCs) in medical school mark the transition
      of students to medicine, beginning their professional identity formation as a
      physician. However, a literature/web search revealed a paucity of residency
      focused WCCs. Methods: A 90-minute Family Medicine Residency (FM) WCC was
      designed to support residents' professional identity formation as a specialty
      physician. Through faculty narratives and brief histories of the white coat and
      the specialty, the WCC concludes with new residents donning their specialty
      embroidered white coats. A brief e-survey was sent to attendees, and WCC leaders
      were debriefed to determine the value and key elements of WCC. Results: Seventy
      nine percent of survey respondents (34/43) agreed that the WCC is an important
      transition event for residents' identity while reaffirming FM values for
      faculty/staff. WCC leaders identified critical steps for initiating a WCC.
      Conclusion: A resident WCC formally marks the transition to specialty physician
      identity. Lessons Learned: Ceremony structure will evolve over time.

PMID- 29349317
TI  - Integration of Point-of-Care Ultrasound Training into Undergraduate Medical
      Curricula--A Perspective from Medical Students.
AB  - The utility of point of care ultrasound training during medical school is
      becoming more and more evident. At the Loma Linda University School of Medicine,
      we have formally integrated ultrasound education into the curriculum of all four
      years. Exposure begins in the first few months of Year 1 and takes form in a
      variety of educational mediums through Year 4. Whether students receive training
      through mandatory sessions during physical diagnosis courses or extracurricular
      workshops provided through the Ultrasound Interest Group--the experience equips
      learners of at all different skill levels with the confidence to apply what they
      have learned to patient care. The successful integration of ultrasound training
      into the medical curriculum can be attributed to progressive administration,
      devoted faculty and eager students. The perspective of medical students during
      the integration process is described in this paper.

PMID- 29349318
TI  - Development of a Course-Based Undergraduate Research Experience to Introduce Drug
      Receptor Concepts.
AB  - Course-based research experiences (CUREs) are currently of high interest due to
      their potential for engaging undergraduate students in authentic research and
      maintaining their interest in science, technology, engineering, and mathematics
      (STEM) majors. As part of a campus-wide initiative called STEMCats, which is a
      living learning program offered to freshman STEM majors at the University of
      Kentucky funded by a grant from Howard Hughes Medical Institute, we have
      developed a CURE for freshmen interested in pursuing health care careers. Our
      course, entitled "Drug-Drug Interactions in Breast Cancer," utilized a semester
      long, in-class authentic research project and instructor-led discussions to
      engage students in a full spectrum of research activities, ranging from
      developing hypotheses and experimental design to generating original data,
      collaboratively interpreting results and presenting a poster at a campus-wide
      symposium. Student's feedback indicated a positive impact on scientific
      understanding and skills, enhanced teamwork and communication skills, as well as
      high student engagement, motivation, and STEM belonging. STEM belonging is
      defined as the extent to which a student may view the STEM fields as places where
      they belong. The results obtained from this pilot study, while preliminary, will
      be useful for guiding design revisions and generating appropriate objective
      evaluations of future pharmacological-based CUREs.

PMID- 29349319
TI  - Encouraging Subspecialty Practice by Constructively Influencing Trainees Early in
      their Careers Will Improve Advocacy for Neuro-Ophthalmology among Nigerian
      Ophthalmologists.
AB  - This study was conducted to assess the current knowledge, attitude, and
      perception of Nigerian ophthalmologists toward neuro-ophthalmology; identify
      barriers to the uptake of neuro-ophthalmology as a desired subspecialty; and make
      recommendations to improve interest in neuro-ophthalmology training. This was a
      cross-sectional survey of ophthalmology consultants and trainees from the six
      geopolitical zones of Nigeria, who were attending a national ophthalmology
      conference. All consenting respondents voluntarily completed a validated self
      administered questionnaire. There were 107 respondents comprising 56 males and 51
      females. Majority (54.2%) of respondents were aged 40 years and younger. Almost
      half (47.8%) worked at tertiary level, public health institutions. Only 10.3%
      worked in private practice. Neuro-ophthalmology exposure was short and occurred
      mainly during residency (65.7%), while 15% had no exposure at all. Most (80.4%)
      indicated only nominal interest in neuro-ophthalmology, while only 4.6% indicated
      a desire to specialize in the field. Financial constraint was the main obstacle
      to the pursuit of subspecialty training. A total of 86% of respondents admitted
      that full (34%) or partial (52%) Funding would motivate them to pursue the
      training. Among respondents desiring part sponsorship, more than half were
      willing to augment such sponsorship with personal funds. In conclusion, career
      interest in neuro-ophthalmology is very low among Nigerian ophthalmologists. Late
      and limited exposure to neuro-ophthalmology during medical training may be
      contributing factors. Early exposure to neuro-ophthalmology during medical school
      rotations, coupled with the provision of sponsored subspecialty training
      opportunities, will serve to increase enrollment in the field.

PMID- 29349320
TI  - Reactions to Diversity: Using Theater to Teach Medical Students about Cultural
      Diversity.
AB  - Training medical students to understand the effects of culture and
      marginalization on health outcomes is important to the future health of
      increasingly diverse populations. We devised and evaluated a short training
      module on working with diversity to challenge students' thinking about the role
      of both patient and practitioner culture in health outcomes. The workshop
      combined didactic teaching about culture as a social determinant of health using
      the cultural humility model, interactive exercises, and applied theater
      techniques. We evaluated changes in the students' perceptions and attitudes over
      time using the Reaction to Diversity Inventory. There was initial significant
      improvement. Women and students with no past diversity training responded best.
      However, scores largely reverted to baseline over 12 months.

PMID- 29349321
TI  - Assessment of Clinical Reasoning by Listening to Case Presentations: VSOP Method
      for Better Feedback.
AB  - Case presentation is used as a teaching and learning tool in almost all clinical
      education, and it is also associated with clinical reasoning ability. Despite
      this, no specific assessment tool utilizing case presentations has yet been
      established. SNAPPS (summarize, narrow, analyze, probe, plan, and select) and the
      One-minute Preceptor are well-known educational tools for teaching how to improve
      consultations. However, these tools do not include a specific rating scale to
      determine the diagnostic reasoning level. Mini clinical evaluation exercise (Mini
      CEX) and RIME (reporter, interpreter, manager, and educator) are comprehensive
      assessment tools with appropriate reliability and validity. The vague,
      structured, organized and pertinent (VSOP) model, previously proposed in Japan
      and derived from RIME model, is a tool for formative assessment and teaching of
      trainees through case presentations. Uses of the VSOP model in real settings are
      also discussed.

PMID- 29349322
TI  - Key Points to Facilitate the Adoption of Computer-Based Assessments.
AB  - There are strong pedagogical arguments in favor of adopting computer-based
      assessment. The risks of technical failure can be managed and are offset by
      improvements in cost-effectiveness and quality assurance capability. Academic,
      administrative, and technical leads at an appropriately senior level within an
      institution need to be identified, so that they can act as effective advocates.
      All stakeholder groups need to be represented in undertaking a detailed appraisal
      of requirements and shortlisting software based on core functionality, summative
      assessment life cycle needs, external compatibility, security, and usability. Any
      software that is a candidate for adoption should be trialed under simulated
      summative conditions, with all stakeholders having a voice in agreeing the
      optimum solution. Transfer to a new system should be carefully planned and
      communicated, with a programme of training established to maximize the success of
      adoption.

PMID- 29349323
TI  - Online Learning Tools as Supplements for Basic and Clinical Science Education.
AB  - Undergraduate medical educators are increasingly incorporating online learning
      tools into basic and clinical science curricula. In this paper, we explore the
      diversity of online learning tools and consider the range of applications for
      these tools in classroom and bedside learning. Particular advantages of these
      tools are highlighted, such as delivering foundational knowledge as part of the
      "flipped classroom" pedagogy and for depicting unusual physical examination
      findings and advanced clinical communication skills. With accelerated use of
      online learning, educators and administrators need to consider pedagogic and
      practical challenges posed by integrating online learning into individual
      learning activities, courses, and curricula as a whole. We discuss strategies for
      faculty development and the role of school-wide resources for supporting and
      using online learning. Finally, we consider the role of online learning in
      interprofessional, integrated, and competency-based applications among other
      contemporary trends in medical education are considered.

PMID- 29349324
TI  - Engagement Patterns of High and Low Academic Performers on Facebook Anatomy
      Pages.
AB  - Only a few studies have investigated how students use and respond to social
      networks in the educational context as opposed to social use. In this study, the
      engagement of medical students on anatomy Facebook pages was evaluated in view of
      their academic performance. High performers contributed to most of the
      engagements. They also had a particular preference for higher levels of
      engagement. Although the students were deeply involved in the educational element
      of the pages, they continued to appreciate the inherent social element. The
      profound engagement of the high performers indicated a consistency between
      Facebook use in the educational context and better student performance. At the
      same time, the deeper engagement of high performers refutes the opinion that
      Facebook use is a distractor. Instead, it supports the notion that Facebook could
      be a suitable platform to engage students in an educational context.

PMID- 29349325
TI  - Back to the Future: What Learning Communities Offer to Medical Education.
AB  - Learning communities (LCs) have increasingly been incorporated into undergraduate
      medical education at a number of medical schools in the United States over the
      past decade. In an Association of Medical Colleges survey of 140 medical schools,
      102 schools indicated that they had LC (described as colleges or mentorship
      groups; https://www.aamc.org/initiatives/cir/425510/19a.html). LCs share an
      overarching principle of establishing longitudinal relationships with students
      and faculty, but differ in the emphasis on specific components that may include
      curriculum delivery, advising/ mentoring, student wellness, and community. The
      creation of LCs requires institutional commitment to reorganize educational
      processes to become more student centered. LCs are beginning to show positive
      outcomes for students including benefits related to clinical skills development,
      advising, and student wellness, in addition to positive outcomes for LC faculty.

PMID- 29349326
TI  - Active Learning in Medical Education: Application to the Training of Surgeons.
AB  - Our article defines active learning in the context of surgical education and
      reviews the growing body of research on new approaches to teaching. We then
      discuss future perspectives and the challenges faced by the trainee and surgeon
      in applying active learning to surgical training. As modern surgical education
      faces numerous challenges, we hope our article will help surgical educators in
      the evaluation of curriculum development, methods of instruction, and assessment.

PMID- 29349327
TI  - Faculty Development on Clinical Teaching Skills: An Effective Model for the Busy
      Clinician.
AB  - Introduction: The authors developed and evaluated a faculty development program
      on clinical teaching skills to address barriers to participation and to impact
      teaching behaviors. Methods: Four one-hour workshops were implemented over five
      months. Evaluation included participant satisfaction and pre/post self
      assessment. Pre/post faculty teaching ratings by trainees were compared. Results:
      A total of 82% of faculty (N = 41) attended. Participants rated workshops highly
      (mean, 4.43/5.00). Self-assessment of skills and comfort with teaching activities
      improved. A total of 59% of residents and 40% of fellows felt that teaching
      received from participating faculty was highly effective. The majority observed
      targeted teaching behaviors by the faculty. Teaching ratings improved after the
      workshops (P = 0.042). Conclusion: Our series of short workshops during a
      standing conference time was associated with increased self-assessed skill and
      comfort and an increase in faculty ratings on teaching evaluations. Effective
      faculty development programs can be implemented in flexible formats and overcome
      common barriers to participation.

PMID- 29349328
TI  - Clinical Correlations as a Tool in Basic Science Medical Education.
AB  - Clinical correlations are tools to assist students in associating basic science
      concepts with a medical application or disease. There are many forms of clinical
      correlations and many ways to use them in the classroom. Five types of clinical
      correlations that may be embedded within basic science courses have been
      identified and described. (1) Correlated examples consist of superficial clinical
      information or stories accompanying basic science concepts to make the
      information more interesting and relevant. (2) Interactive learning and
      demonstrations provide hands-on experiences or the demonstration of a clinical
      topic. (3) Specialized workshops have an application-based focus, are more
      specialized than typical laboratory sessions, and range in complexity from basic
      to advanced. (4) Small-group activities require groups of students, guided by
      faculty, to solve simple problems that relate basic science information to
      clinical topics. (5) Course-centered problem solving is a more advanced
      correlation activity than the others and focuses on recognition and treatment of
      clinical problems to promote clinical reasoning skills. Diverse teaching
      activities are used in basic science medical education, and those that include
      clinical relevance promote interest, communication, and collaboration, enhance
      knowledge retention, and help develop clinical reasoning skills.

PMID- 29349329
TI  - Using Learner-Centered, Simulation-Based Training to Improve Medical Students'
      Procedural Skills.
AB  - Purpose: To evaluate the effectiveness of a learner-centered, simulation-based
      training developed to help medical students improve their procedural skills in
      intubation, arterial line placement, lumbar puncture, and central line insertion.
      Method: The study participants were second and third year medical students.
      Anesthesiology residents provided the training and evaluated students' procedural
      skills. Two residents were present at each station to train the medical students
      who rotated through all 4 stations. Pre/posttraining assessment of confidence,
      knowledge, and procedural skills was done using a survey, a multiple-choice test,
      and procedural checklists, respectively. Results: In total, 24 students were
      trained in six 4-hour sessions. Students reported feeling significantly more
      confident, after training, in performing all 4 procedures on a real patient (P <
      .001). Paired-samples t tests indicated statistically significant improvement in
      knowledge scores for intubation, t(23) = -2.92, P < .001, and arterial line
      placement, t(23) = -2.75, P < .001. Procedural performance scores for intubation
      (t(23) = -17.29, P < .001), arterial line placement (t(23) = -19.75, P < .001),
      lumbar puncture (t(23) = -16.27, P < .001), and central line placement (t(23) = 
      17.25, P < .001) showed significant improvement. Intraclass correlation
      coefficients indicated high reliability in checklist scores for all procedures.
      Conclusions: The simulation sessions allowed each medical student to receive
      individual attention from 2 residents for each procedure. Students' written
      comments indicated that this training modality was well received. Results showed
      that medical students improved their self-confidence, knowledge, and skills in
      the aforementioned procedures.

PMID- 29349330
TI  - 'Involve Me and I Learn': Development of an Assessment Program for Research and
      Critical Analysis.
AB  - Evidence-based medical practice is best achieved by developing research
      understanding in medical practitioners. To this end, medical councils worldwide
      increasingly recognise the importance of medical schools graduating students with
      well-developed research skills and research capacity. To meet this need, the
      principles of programmatic assessment were implemented in designing a research
      and critical analysis curriculum and assessment program that aimed to enhance the
      research and critical analysis skills of medical students. The program was
      developed by mapping assessment tasks to a research capabilities framework that
      was in turn scaffolded to different levels of Miler's pyramid. The curriculum and
      assessments were integrated with the science, clinical, and professional aspects
      of the medical course. The progressive longitudinal development of research
      skills, with feedback and academic mentoring, culminated in the students'
      capacity to undertake an independent research project. Designing an assessment
      program for learning encouraged students to develop their research capacity by
      involving them in their learning.

PMID- 29349331
TI  - "Thank You for Giving Me a Voice!" A Longitudinal Evaluation of Patients'
      Experience of Partnering With Students in an Australian Medical School.
AB  - Background: We evaluated the patient-partner experience in a longitudinal program
      called Integrated Population Medicine in the Sydney Medical School to assess its
      acceptability. The program exposed senior medical students to the lived
      experience of chronic disease. Methods: We surveyed 267 people with chronic
      conditions recruited as patient-partners by the 2012 student cohort in a mixed
      methods longitudinal cohort study. Surveys were administered 'over' 18 months:
      before, during, and after the program. Results: A total of 155 (58%) patient
      partners completed the baseline survey; 52 patients returned all 3 surveys.
      Patient-partners remained very positive about the program across all surveys.
      More than 95% of respondents enjoyed interacting with the student, and most were
      very positive about their role in teaching the student. Three major themes
      emerged: willingness to help, a sense of gratitude and enjoyment, and a chance to
      teach and learn. Participants were willing to discuss their illness experiences
      and were keen to spend more time with students. Conclusions: Patients are willing
      participants in longitudinal patient-partner programs. They perceive benefits for
      themselves and others, for the health system, and for students and would like to
      become more actively involved in medical education.

PMID- 29349332
TI  - Teaching Critical Thinking in Graduate Medical Education: Lessons Learned in
      Diagnostic Radiology.
AB  - The 2014 Institute of Medicine report, Graduate Medical Education that Meets the
      Nation's Health Needs, challenged the current graduate medical training process
      and encouraged new opportunities to redefine the fundamental skills and abilities
      of the physician workforce. This workforce should be skilled in critically
      evaluating the current systems to improve care delivery and health. To meet these
      goals, current challenges, motivations, and educational models at the medical
      school and graduate medical education levels related to formal training in
      nonclinical aspects of medicine, especially critical thinking, are reviewed. Our
      diagnostic radiology training program is presented as a "case study" to frame the
      review.

PMID- 29349334
TI  - Assessing the Current Curriculum of the Nursing and Midwifery Informatics Course
      at All Nursing and Midwifery Institutions in Ghana.
AB  - The use of computers in the delivery of health care has significantly improved
      the way health service is delivered to clients and patients in the world. Despite
      the importance of computing to the delivery of health service, developing
      countries have not greatly benefited from it. Nursing informatics has been in
      existence and part of academic curriculum for the past 2 decades in some advanced
      countries. The Ghana Nursing and Midwifery Council introduced the nursing and
      midwifery informatics course during the 2015/2016 academic year. This seeks to
      train student nurses on the relevance of computers to health care. Two separate
      workshops were organised to ascertain the preparedness of tutors (teachers at the
      nursing and midwifery training institutions) for teaching the new nursing and
      midwifery informatics course as well as to compare the curriculum with other
      international recommendations. The nursing and midwifery informatics course is
      taught at the first year where students have not been introduced to the nursing
      processes for them to appreciate the use of nursing informatics skills. It would
      be better if the nursing and midwifery informatics course is rather introduced
      during the second year second semester when students are about going for the
      hands-on training at the various health care institutions. Examining the course
      content reveals that the practical aspect within the course is very small. It is
      expected that more practical contents will be introduced. Tutors are not
      adequately prepared to teach this new course. More training is therefore needed
      to make tutors fully prepared to teach both the theory and practical aspects of
      the nursing and midwifery informatics course. It is expected that the nursing and
      midwifery informatics course would prepare student nurses on all nursing
      informatics competencies. It is essential that nurse educators incorporate the
      entire concept of informatics into the education of nurses.

PMID- 29349333
TI  - What Influences Mental Illness? Discrepancies Between Medical Education and
      Conception.
AB  - Objective: This preliminary study examined the differences between what was
      taught during a formal medical education and medical students' and psychiatry
      residents' conceptions of notions regarding the causes and determinants of mental
      illness. Methods: The authors surveyed 74 medical students and 11 residents via
      convenience sampling. The survey contained 18 statements which were rated twice
      based on truthfulness in terms of a participant's formal education and
      conception, respectively. Descriptive statistics and a Wilcoxon signed rank test
      determined differences between education and conception. Results: Results showed
      that students were less likely to perceive a neurotransmitter imbalance to cause
      mental illness, as opposed to what was emphasized during a formal medical
      education. Students and residents also understood the importance of factors such
      as systemic racism and socioeconomic status in the development of mental illness,
      which were factors that did not receive heavy emphasis during medical education.
      Furthermore, students and residents believed that not only did mental illnesses
      have nonuniform pathologies, but that the Diagnostic and Statistical Manual of
      Mental Disorders also had the propensity to sometimes arbitrarily categorize
      individuals with potentially negative consequences. Conclusions: If these notions
      are therefore part of students' and residents' conceptions, as well as documented
      in the literature, then it seems appropriate for medical education to be further
      developed to emphasize these ideas.

PMID- 29349335
TI  - An Innovative Clinical Skills "Boot Camp" for Dental Medicine Residents.
AB  - During a 1-year hospital-based residency, dental residents are required to rotate
      through many departments including surgery, medicine, and emergency medicine. It
      became apparent that there was a gap between clinical skills knowledge taught in
      dental school curriculum and skills required for hospital-based patient care. In
      response, a simulation-based intensive clinical skill "boot camp" was created.
      The boot camp provided an intensive, interactive 3-day session for the dental
      residents. During the 3 days, residents were introduced to medical knowledge and
      skills that were necessary for their inpatient hospital rotations but were
      lacking in traditional dental school curriculum. Effectiveness of the boot camp
      was assessed in terms of knowledge base and comfort through presession and
      postsession surveys. According to resident feedback, this intensive introduction
      for the dental residents improved their readiness for their inpatient hospital
      based residency.

PMID- 29349336
TI  - Interactive Journal Club: Teaching an Old Dog New Tricks.
AB  - The interactive journal club incorporates basic principles of active and adult
      learning in a traditional education tool to maximize opportunity to develop
      critical thinking, communication skills, active reflection, and personal
      confidence in these skills. Following the choice of an appropriate article, the
      Designated Leader (DL) directs the discussion by presenting the title and data
      from the article with instructions for their analysis but without the author's
      text. The participants, except the DL, are viewing the article for the first time
      and are prompted in their review of the raw data to provide their own
      interpretation, discovery, and critique. Participants are challenged to become
      more adept at study design, data analysis, and presentation and have indicated by
      informal verbal feedback that they look forward to the interactive journal club
      as it is enjoyable, relevant, and beneficial. Implementation of the interactive
      journal club does not require significant training in the approach or extensive
      revision or preparation of course materials.

PMID- 29349337
TI  - The Relationship Between Method of Viewing Lectures, Course Ratings, and Course
      Timing.
AB  - Background: In recent years, medical schools have provided students access to
      video recordings of course lectures, but few studies have investigated the impact
      of this on ratings of courses and teachers. This study investigated whether the
      method of viewing lectures was related to student ratings of the course and its
      components and whether the method used changed over time. Methods: Preclinical
      medical students indicated whether ratings of course lectures were based
      primarily on lecture attendance, video capture, or both. Students were
      categorized into Lecture, Video, or Both groups based on their responses to this
      question. The data consisted of 7584 student evaluations collected over 2 years.
      Results: Students who attended live lectures rated the course and its components
      higher than students who only viewed the video or used both methods, although
      these differences were very small. Students increasingly watched lectures
      exclusively by video over time: in comparison with first-year students, second
      year students were more likely to watch lectures exclusively by video; in
      comparison with students in the first half of the academic year, students in the
      second half of the academic year were more likely to watch lectures exclusively
      by video. Conclusions: With the increase in use of lecture video recordings
      across medical schools, attention must be paid to student attitudes regarding
      these methods.

PMID- 29349338
TI  - The Effectiveness of Computer-Assisted Instruction to Teach Physical Examination
      to Students and Trainees in the Health Sciences Professions: A Systematic Review
      and Meta-Analysis.
AB  - Purpose: To explore knowledge and skill acquisition outcomes related to learning
      physical examination (PE) through computer-assisted instruction (CAI) compared
      with a face-to-face (F2F) approach. Method: A systematic literature review and
      meta-analysis published between January 2001 and December 2016 was conducted.
      Databases searched included Medline, Cochrane, CINAHL, ERIC, Ebsco, Scopus, and
      Web of Science. Studies were synthesized by study design, intervention, and
      outcomes. Statistical analyses included DerSimonian-Laird random-effects model.
      Results: In total, 7 studies were included in the review, and 5 in the meta
      analysis. There were no statistically significant differences for knowledge (mean
      difference [MD] = 5.39, 95% confidence interval [CI]: -2.05 to 12.84) or skill
      acquisition (MD = 0.35, 95% CI: -5.30 to 6.01). Conclusions: The evidence does
      not suggest a strong consistent preference for either CAI or F2F instruction to
      teach students/trainees PE. Further research is needed to identify conditions
      which examine knowledge and skill acquisition outcomes that favor one mode of
      instruction over the other.

PMID- 29349339
TI  - The Impact of a Revised Curriculum on Academic Motivation, Burnout, and Quality
      of Life Among Medical Students.
AB  - Objective: The purpose of this study was to determine the impact of a revised
      curriculum on medical student academic motivation, burnout, and quality of life.
      Methods: This cross-sectional comparative study involved 2 medical school cohorts
      of second year and fourth year medical students at The University of Auckland: a
      cohort under a traditional curriculum (n = 437) and a cohort under a revised
      curriculum (n = 446). Participants completed self-reported questionnaires
      measuring academic motivation, burnout, and quality of life. Two multivariate
      analyses of covariance (MANCOVAs) were conducted. Results: The response rate was
      48%. No statistically significant differences were found between curriculum
      cohorts for mean scores of academic motivation, personal burnout, and quality of
      life. However, differences were found when comparing preclinical medical students
      and students in their clinical years of training. In comparison with Year 2
      medical students, the MANCOVA for Year 4 students showed a significant main
      effect for the revised curriculum with respect to both physical and environmental
      quality of life. Conclusions: A revised medical curriculum had a differential
      effect on quality of life for Year 4 students in the latter years of medical
      school who are based in a clinical learning environment.

PMID- 29349340
TI  - Journeying to the White Coat Ceremony: A description of the people, situations
      and experiences that inform student visions of the physician they hope to become.
AB  - Little is known about the experiences that influence entering medical students'
      internal concepts of themselves as future physicians. During orientation to
      medical school, students were asked to write stories in response to the cue,
      "Tell a story about a person or experience that inspired you to consider a career
      of service in medicine." Qualitative methodology was employed to analyze 190
      student stories. Thematic analysis identified descriptive details about content
      and allowed comparison between the students' and School's expectations.
      Inspirational settings, contexts, and individuals were identified. Nine different
      inspirational events were described. Student and School expectations for the
      kinds of physicians they hoped to become were generally consistent. The study
      demonstrates that students do indeed bring to medical school visions of the kinds
      of physicians they hope to become. Linking that vision with medical school
      activities including the White Coat Ceremony provides a bridge between medical
      school and students' earlier lives, thus explicitly linking orientation to
      professional formation.

PMID- 29349341
TI  - Why People Apply to Medical School in Iraq?
AB  - Background: The motivations behind why people choose to study medicine in Iraqi
      medical schools are unknown. Such information could help school pupils to make
      more informed career decisions and assist medical schools in enhancing the
      student selection process. Aims: To investigate why people choose to study
      medicine in Iraq. Subjects and methods: The first-year students admitted on the
      academic year 2015-2016 to Baghdad College of Medicine, University of Baghdad,
      were invited to complete a structured questionnaire, which was administered
      through the college electronic education portal. The data were analyzed using IBM
      SPSS version 21 software. Results: A total of 152 (50% response rate) students
      responded. Women constituted 69.1% of respondents. Most students (61.8%) had made
      their choice by themselves without family pressure. The most frequent reasons
      that affected this choice were "humanitarian reasons and a wish to provide help
      to others" as well as "childhood dream," "positive community appraisal of
      doctors," and "ready availability of work for physicians." About three-quarters
      (73.6%) of the students made some inquiry about medical school before making
      their choice, and the people asked were most frequently a medical student or a
      doctor. Information provided by the consulted parties was regarded as
      satisfactory by 64.2% of the surveyed students, had a positive value in 47.2%,
      and affected their decision in 34.9%. The highest proportion (42.2%) of the study
      sample was thinking about studying medicine since primary school. In addition,
      students with personal preference made their choice at a significantly younger
      age. Conclusions: Reasons to apply for medical schools in Iraq are similar to
      those in many countries. Most of the students who inquired about studying
      medicine had not contacted the medical school itself.

PMID- 29349342
TI  - No Ifs, Ands, or Buts: Leveraging Population Health to Focus on the Care of
      Patients Who Smoke.
AB  - We developed a multidisciplinary curriculum to improve our residents' proficiency
      with smoking cessation counseling and prescribing of nicotine replacement therapy
      (NRT). The curriculum included a didactic portion, informational handouts, and a
      panel management component during which residents did telephone outreach and
      clinic in-reach to address high rates of smoking among patients. Residents rated
      their confidence with smoking cessation counseling and clinical knowledge before
      and after the intervention. We also tracked the number of patients flagged in the
      electronic medical record as smokers, the number of patients contacted, and the
      number of patients who received counseling. Although we did not make
      statistically significant improvements in perceived confidence with prescribing
      NRT, we found that there is an urgent need to address smoking cessation in the
      primary care setting and that working with a clinical pharmacist and psychologist
      offered a comprehensive approach. Furthermore, by anchoring the intervention with
      a population health component, almost 200 patients benefited from outreach
      efforts.

PMID- 29349343
TI  - Increasing Medical Trainees' Empathy Through Volunteerism and Mentorship.
AB  - Background: Within medical education, there have been recent calls for increased
      understanding and exposure to poverty to increase trainees' empathy toward the
      underserved. Students participating in Michigan Cardiovascular Outcomes Research
      and Reporting Program research program volunteered at World Medical Relief (WMR)
      in Detroit, Michigan, a nonprofit organization which recycles medical equipment
      for developing countries and within greater Detroit. Participants' perceptions of
      the underserved were measured before and after the experience. Methods:
      Preliminary questionnaires were given to participants prior to and after
      exposures at WMR. Questionnaires examined participants' attitudes toward the
      underserved, knowledge of medical supply reuse, and their perceived ability to
      impact change. P values of <.025 were considered significant. Results: A total of
      39 participants completed the survey, 77% previously volunteered, 33% had
      volunteered internationally. Participants were >4* more likely than previously to
      have knowledge of the variety of recycled medical supplies at WMR. Prior to
      volunteering, 48.7% of participants gave little thought to how excess medical
      supplies could be collected versus 0% after exposure. Participants were 1.5* more
      likely to agree that the experience was enhanced working with their peers and
      2.7* more likely to consider starting their own organization/intervention for
      medical supply donations. Those participants that never previously volunteered
      were 1.3* more likely to do so with encouragement from a mentor. Conclusions:
      Encouraging exposure to such service programs resulted in enhanced knowledge of
      community resources and increased motivation to participate in outreach and
      belief of individual responsibility to care for the underserved. Incorporating
      volunteerism into traditional education programs offers the opportunity to build
      awareness and interest in students reaching out to the underserved.

PMID- 29349344
TI  - Adaptation and Evaluation of Military Resilience Skills Training for Pediatric
      Residents.
AB  - Background: An evidence-based trauma-informed resilience skills training program
      developed for deployed military personnel was adapted and pilot-tested with
      pediatric residents. We anticipated high satisfaction ratings and changes in
      knowledge, beliefs, and self-efficacy related to coping with stress and trauma.
      Methods: The intervention included 6 skill-based modules covering emotion
      regulation, communication with angry patients and parents, reflective narrative,
      inspirational goal setting, problem-solving, and developing a self-care toolbox.
      An optional survey was administered before and after the training. Results: After
      training, 76% rated resilience skills as important, 60% were satisfied, and 82%
      indicated the training changed how they will respond to patient-related grief and
      trauma. They became more likely to believe attendings are affected by patient
      deaths and to know what helps them cope when they disagree with the medical
      decision making of others, more skilled in recognizing signs of stress and
      trauma, and more knowledgeable about evidence-based interventions.

PMID- 29349345
TI  - Medical Student Perceptions of Learner-Initiated Feedback Using a Mobile Web
      Application.
AB  - Feedback, especially timely, specific, and actionable feedback, frequently does
      not occur. Efforts to better understand methods to improve the effectiveness of
      feedback are an important area of educational research. This study represents
      preliminary work as part of a plan to investigate the perceptions of a student
      driven system to request feedback from faculty using a mobile device and Web
      based application. We hypothesize that medical students will perceive learner
      initiated, timely feedback to be an essential component of clinical education.
      Furthermore, we predict that students will recognize the use of a mobile device
      and Web application to be an advantageous and effective method when requesting
      feedback from supervising physicians. Focus group data from 18 students enrolled
      in a 4-week anesthesia clerkship revealed the following themes: (1) students
      often have to solicit feedback, (2) timely feedback is perceived as being
      advantageous, (3) feedback from faculty is perceived to be more effective, (4)
      requesting feedback from faculty physicians poses challenges, (5) the decision to
      request feedback may be influenced by the student's clinical performance, and (6)
      using a mobile device and Web application may not guarantee timely feedback.
      Students perceived using a mobile Web-based application to initiate feedback from
      supervising physicians to be a valuable method of assessment. However, challenges
      and barriers were identified.

PMID- 29349346
TI  - Characteristics of electroencephalogram signatures in sedated patients induced by
      various anesthetic agents.
AB  - Devices that monitor the depth of hypnosis based on the electroencephalogram
      (EEG) have long been commercialized, and clinicians use these to titrate the
      dosage of hypnotic agents. However, these have not yet been accepted as standard
      monitoring devices for anesthesiology. The primary reason is that the use of
      these monitoring devices does not completely prevent awareness during surgery,
      and the development of these devices has not taken into account the
      neurophysiological mechanisms of hypnotic agents, thus making it possible to show
      different levels of unconsciousness in the same brain status. An alternative is
      to monitor EEGs that are not signal processed with numerical values presented by
      these monitoring devices. Several studies have reported that power spectral
      analysis alone can distinguish the effects of different hypnotic agents on
      consciousness changes. This paper introduces the basic concept of power spectral
      analysis and introduces the EEG characteristics of various hypnotic agents that
      are used in sedation.

PMID- 29349347
TI  - Pain measurement in oral and maxillofacial surgery.
AB  - Regardless of whether it is acute or chronic, the assessment of pain should be
      simple and practical. Since the intensity of pain is thought to be one of the
      primary factors that determine its effect on a human's overall function and
      sense, there are many scales to assess pain. The aim of the current article was
      to review pain intensity scales that are commonly used in dental and oral and
      maxillofacial surgery (OMFS). Previous studies demonstrated that multidimensional
      scales, such as the McGill Pain Questionnaire, Short form of the McGill Pain
      Questionnaire, and Wisconsin Brief Pain Questionnaire were suitable for assessing
      chronic pain, while unidimensional scales, like the Visual Analogue Scales (VAS),
      Verbal descriptor scale, Verbal rating scale, Numerical rating Scale, Faces Pain
      Scale, Wong-Baker Faces Pain Rating Scale (WBS), and Full Cup Test, were used to
      evaluate acute pain. The WBS is widely used to assess pain in children and
      elderly because other scales are often difficult to understand, which could
      consequently lead to an overestimation of the pain intensity. In dental or OMFS
      research, the use of the VAS is more common because it is more reliable, valid,
      sensitive, and appropriate. However, some researchers use NRS to evaluate OMFS
      pain in adults because this scale is easier to use than VAS and yields relatively
      similar pain scores. This review only assessed pain scales used for post
      operative OMFS or dental pain.

PMID- 29349348
TI  - The effect of tulobuterol patches on the respiratory system after endotracheal
      intubation.
AB  - Background: Endotracheal intubation during anesthesia induction may increase
      airway resistance (Raw) and decrease dynamic lung compliance (Cdyn). We
      hypothesized that prophylactic treatment with a transdermal beta2-agonist
      tulobuterol patch (TP) would help to reduce the risk of bronchospasm after
      placement of the endotracheal tube. Methods: Eighty-two American Society of
      Anesthesiologists (ASA) category I or II adult patients showing obstructive
      patterns were divided randomly into a control and a TP group (n = 41 each). The
      night before surgery, a 2-mg TP was applied to patients in the TP group. Standard
      monitors were recorded, and target controlled infusion (TCI) with propofol and
      remifentanil was used for anesthesia induction and maintenance. Simultaneously,
      end-tidal carbon dioxide, Raw, and Cdyn were determined at 5, 10, and 15 min
      intervals after endotracheal intubation. Results: There was no significant
      difference in demographic data between the two groups. The TP group was
      associated with a lower Raw and a higher Cdyn, as compared to the control group.
      Raw was significantly lower at 10 min (P < 0.05) and 15 min (P < 0.01), and Cdyn
      was significantly higher at 5 min (P < 0.05) and 15 min (P < 0.01) in the TP
      group. A trend towards a lower Raw was observed showing a statistically
      significant difference 5 min after endotracheal intubation (P < 0.01) in each
      group. Conclusions: Prophylactic treatment with TP showed a bronchodilatory
      effect through suppressing an increase in Raw and a decrease in Cdyn after
      anesthesia induction without severe adverse effects.

PMID- 29349349
TI  - A retrospective analysis of outpatient anesthesia management for dental treatment
      of patients with severe Alzheimer's disease.
AB  - Background: The number of patients with Alzheimer's disease is growing worldwide,
      and the proportion of patients requiring dental treatment under general
      anesthesia increases with increasing severity of the disease. However, outpatient
      anesthesia management for these patients involves great risks, as most patients
      with Alzheimer's disease are old and may show reduced cardiopulmonary functions
      and have cognitive disorders. Methods: This study retrospectively investigated 43
      patients with Alzheimer's disease who received outpatient anesthesia for dental
      treatment between 2012-2017. Pre-anesthesia patient evaluation, dental treatment
      details, anesthetics dose, blood pressure, duration and procedure of anesthesia,
      and post-recovery management were analyzed and compared between patients who
      underwent general anesthesia or intravenous sedation. Results: Mean age of
      patients was about 70 years; mean duration of Alzheimer's disease since diagnosis
      was 6.3 years. Severity was assessed using the global deterioration scale; 62.8%
      of patients were in level >= 6. Mean duration of anesthesia was 178 minutes for
      general anesthesia and 85 minutes for intravenous sedation. Mean recovery time
      was 65 minutes. Eleven patients underwent intravenous sedation using propofol,
      and 22/32 cases involved total intravenous anesthesia using propofol and
      remifentanil. Anesthesia was maintained with desflurane for other patients. While
      maintaining anesthesia, inotropic and atropine were used for eight and four
      patients, respectively. No patient developed postoperative delirium. All patients
      were discharged without complications. Conclusion: With appropriate anesthetic
      management, outpatient anesthesia was successfully performed without
      complications for dental treatment for patients with severe Alzheimer's disease.

PMID- 29349350
TI  - A comparison of the effects of epinephrine and xylometazoline in decreasing nasal
      bleeding during nasotracheal intubation.
AB  - Background: Various techniques have been introduced to decrease complications
      during nasotracheal intubation. A common practice is to use nasal packing with a
      cotton stick and 0.01% epinephrine jelly. However, this procedure can be painful
      to patients and can damage the nasal mucosa. Xylometazoline spray can induce
      effective vasoconstriction of the nasal mucosa without direct nasal trauma. In
      this study, we aimed to compare the efficacy of these two methods. Methods:
      Patients were randomly allocated into two groups (n = 40 each): xylometazoline
      spray group or epinephrine packing group. After the induction of general
      anesthesia, patients allocated to the xylometazoline spray group were treated
      with xylometazoline spray to induce nasal cavity mucosa vasoconstriction, and the
      epinephrine packing group was treated with nasal packing with two cotton sticks
      and 0.01% epinephrine jelly. The number of attempts to insert the endotracheal
      tube into the nasopharynx, the degree of difficulty during insertion, and
      bleeding during bronchoscopy were recorded. An anesthesiologist, blinded to the
      intubation method, estimated the severity of epistaxis 5 min after intubation and
      postoperative complications. Results: No significant intergroup difference was
      observed in navigability (P = 0.465). The xylometazoline spray group showed
      significantly less epistaxis during intubation (P = 0.02). However, no
      differences were observed in epistaxis 5 min after intubation or postoperative
      epistaxis (P = 0.201). No inter-group differences were observed in complications
      related to nasal intubation and nasal pain. Conclusion: Xylometazoline spray is a
      good alternative to nasal packing for nasal preparation before nasotracheal
      intubation.

PMID- 29349351
TI  - The relationship between subjective oral health and dental fear in Korean
      adolescents.
AB  - Background: This study is aimed to evaluate the level of fear and to reduce the
      overall fear, thereby enabling patients to receive treatment via timely visits.
      Methods: In a survey conducted by 460 South Korean middle school students, we
      used 453 data that faithfully responded to the survey. Multiple regression
      analysis was conducted to investigate the factors influencing subjective oral
      health and dental fear. The significance level used for statistical significance
      was alpha = 0.05. Results: The level of fear was higher for upper grade, female
      students. The factors affecting dental fear were higher for gingival bleeding and
      dental pain. Regarding factors for dental fear affecting subjective oral health,
      lower fear of puncture needle and tooth removal tool resulted in higher
      subjective oral health. Conclusion: The study found that adolescents had higher
      fear of dental care when they had gingival bleeding and tooth pain. Gingival
      bleeding is a symptom of early gingival disease and dental pain is likely due to
      advanced dental caries. These results suggested that it is necessary to have a
      program to reduce dental fear and anxiety as well as a program to prevent dental
      diseases through regular periodic screening and education.

PMID- 29349352
TI  - Learning fiberoptic intubation for awake nasotracheal intubation.
AB  - Background: Fiberoptic nasotracheal intubation (FNI) is performed if it is
      difficult to open the mouth or if intubation using laryngoscope is expected to be
      difficult. However, training is necessary because intubation performed by
      inexperienced operators leads to complications. Methods: Every resident performed
      intubation in 40 patients. Success of FNI was evaluated as the time of FNI. First
      intubation time was restricted to 2 min 30 s. If the second attempt was
      unsuccessful, it was considered a failed case, and a specialist performed
      nasotracheal intubation. If the general method of intubation was expected to be
      difficult, awake intubation was performed. The degree of nasal bleeding during
      intubation was also evaluated. Results: The mean age of the operators (11 men, 7
      women) was 27.8 years. FNI was performed in a total of 716 patients. The success
      rate was 88.3% for the first attempt and 94.6% for the second attempt. The
      failure rate of intubation in anesthetized patients was 4.9%, and 13.6% in awake
      patients. When intubation was performed in anesthetized patients, the failure
      rate from the first to fifth trial was 9.6%, which decreased to 0.7% when the
      number of trials increased to > 30 times. In terms of awake intubation, there was
      no failed attempt when the resident had performed the FNI > 30 times. The number
      of FNIs performed and nasal bleeding were important factors influencing the
      failure rate. Conclusion: The success rate of FNI increased as the number of FNI
      performed by residents increased despite the nasal bleeding.

PMID- 29349353
TI  - Estimation of optimal nasotracheal tube depth in adult patients.
AB  - Background: The aim of this study was to estimate the optimal depth of
      nasotracheal tube placement. Methods: We enrolled 110 patients scheduled to
      undergo oral and maxillofacial surgery, requiring nasotracheal intubation. After
      intubation, the depth of tube insertion was measured. The neck circumference and
      distances from nares to tragus, tragus to angle of the mandible, and angle of the
      mandible to sternal notch were measured. To estimate optimal tube depth,
      correlation and regression analyses were performed using clinical and
      anthropometric parameters. Results: The mean tube depth was 28.9 +/- 1.3 cm in
      men (n = 62), and 26.6 +/- 1.5 cm in women (n = 48). Tube depth significantly
      correlated with height (r = 0.735, P < 0.001). Distances from nares to tragus,
      tragus to angle of the mandible, and angle of the mandible to sternal notch
      correlated with depth of the endotracheal tube (r = 0.363, r = 0.362, and r =
      0.546, P < 0.05). The tube depth also correlated with the sum of these distances
      (r = 0.646, P < 0.001). We devised the following formula for estimating tube
      depth: 19.856 + 0.267 * sum of the three distances (R2 = 0.432, P < 0.001).
      Conclusion: The optimal tube depth for nasotracheally intubated adult patients
      correlated with height and sum of the distances from nares to tragus, tragus to
      angle of the mandible, and angle of the mandible to sternal notch. The proposed
      equation would be a useful guide to determine optimal nasotracheal tube
      placement.

PMID- 29349354
TI  - Awake intubation in a patient with huge orocutaneous fistula: a case report.
AB  - Mask ventilation, the first step in airway management, is a rescue technique when
      endotracheal intubation fails. Therefore, ordinary airway management for the
      induction of general anesthesia cannot be conducted in the situation of difficult
      mask ventilation (DMV). Here, we report a case of awake intubation in a patient
      with a huge orocutaneous fistula. A 58-year-old woman was scheduled to undergo a
      wide excision, reconstruction with a reconstruction plate, and supraomohyoid neck
      dissection on the left side and an anterolateral thigh flap due to a huge
      orocutaneous fistula that occurred after a previous mandibulectomy and flap
      surgery. During induction, DMV was predicted, and we planned an awake intubation.
      The patient was sedated with dexmedetomidine and remifentanil. She was intubated
      with a nasotracheal tube using a video laryngoscope, and spontaneous ventilation
      was maintained. This case demonstrates that awake intubation using a video
      laryngoscope can be as good as a fiberoptic scope.

PMID- 29349355
TI  - Facial blanching after inferior alveolar nerve block anesthesia: an unusual
      complication.
AB  - The present case report describes a complication involving facial blanching
      symptoms occurring during inferior alveolar nerve block anesthesia (IANBA).
      Facial blanching after IANBA can be caused by the injection of an anesthetic into
      the maxillary artery area, affecting the infraorbital artery.

PMID- 29349356
TI  - QT-interval prolongation due to medication found in the preoperative evaluation.
AB  - QT prolongation is an electrocardiographic change that can lead to lethal
      arrhythmia. Acquired QT prolongation is known to be caused by drugs and
      electrolyte abnormalities. We report three cases in which the prolonged QT
      interval was improved at the time of operation by briefly discontinuing the drugs
      suspected to have caused the QT prolongation observed on preoperative
      electrocardiography. The QTc of cases 1, 2, and 3 improved from 518 to 429 ms,
      463 to 441 ms, and 473 to 443 ms on discontinuing the use of a gastrointestinal
      prokinetic agent, a proton pump inhibitor, and a molecular targeted drug,
      respectively. These cases were considered to have drug-induced QT prolongation.
      We reaffirmed that even drugs administered for conditions unrelated to cardiac
      diseases can have adverse side effect of QT prolongation. In conclusion, our
      cases indicate that dental surgeons should be aware of the dangerous and even
      potentially lethal side effects of QT prolongation. For safe oral and
      maxillofacial surgery, cooperation with medical departments in various fields is
      important.

PMID- 29349358
TI  - 95gTc and 96gTc as alternatives to medical radioisotope 99mTc.
AB  - We studied 95gTc and 96gTc as alternatives to the medical radioisotope 99mTc.
      96gTc (95gTc) can be produced by (p, n) reactions on an enriched 96Mo (95Mo)
      target with a proton beam provided by a compact accelerator such as a medical
      cyclotron that generate radioisotopes for positron emission tomography (PET). The
      gamma-rays are measured with an electron-tracking Compton camera (ETCC). We
      calculated the relative intensities of the gamma-rays from 95gTc and 96gTc. The
      calculated gamma-ray intensity of a 96gTc (95gTc) nucleus is as high as 63% (70%)
      of that of a 99mTc nucleus. We also calculated the patient radiation doses of
      95gTc and 96gTc, which were larger than that of 99mTc by a factor of 2-3 based on
      the applied assumptions. A medical PET cyclotron which can provide proton beams
      with energies of 11-12 MeV and a current of 100 MUA can produce 12 GBq (39 GBq)
      of 96gTc (95gTc) for operation time of 8 h, which can be used for 240 (200)
      diagnostic scans.

PMID- 29349359
TI  - Resensitization of methicillin-resistant Staphylococcus aureus by amoxapine, an
      FDA-approved antidepressant.
AB  - The rapid increase in bacterial resistance to antibiotics is a global healthcare
      crisis. Non-antibiotic pharmaceuticals that have attained approval by the United
      States Food and Drug Administration have the potential to be repurposed as
      bacterial resistance-modifying agents and therefore could become valuable
      resources in our battle against antibiotic-resistant microbes. Amoxapine is a
      tetracyclic antidepressant used in the treatment of major depressive disorder.
      Here we demonstrate the ability of amoxapine to resensitize methicillin-resistant
      Staphylococcus aureus strain ATCC 43300 to oxacillin in both agar diffusion and
      broth microdilution assays. Amoxapine also reduced the bacterial cleavage of
      nitrocefin in a dose-dependent manner, suggesting that it may exert its adjuvant
      effects through reduction of beta-lactamase activity.

PMID- 29349357
TI  - Comprehensive cytotoxicity studies of superparamagnetic iron oxide nanoparticles.
AB  - Recently lots of efforts have been taken to develop superparamagnetic iron oxide
      nanoparticles (SPIONs) for biomedical applications. So it is utmost necessary to
      have in depth knowledge of the toxicity occurred by this material. This article
      is designed in such way that it covers all the associated toxicity issues of
      SPIONs. It mainly emphasis on toxicity occurred at different levels including
      cellular alterations in the form of damage to nucleic acids due to oxidative
      stress and altered cellular response. In addition focus is been devoted for in
      vitro and in vivo toxicity of SPIONs, so that a better therapeutics can be
      designed. At the end the time dependent nature of toxicity and its ultimate faith
      inside the body is being discussed.

PMID- 29349361
TI  - Endovascular repair of an innominate artery pseudoaneurysm using the Valiant Mona
      LSA branched graft device.
AB  - A 60-year-old woman involved in a motor vehicle collision presented with a
      traumatic pseudoaneurysm of the innominate artery origin in addition to multiple
      concomitant injuries. She was classified as a high-risk candidate for open
      repair. An experimental thoracic branched graft device was used for coverage of
      the injury with the addition of a right carotid-to-left carotid-to-left
      subclavian artery bypass. Follow-up imaging showed resolution of the
      pseudoaneurysm and patency of her bypass grafts. This is the first described use
      of the Mona LSA Branch Thoracic Stent Graft System (Medtronic, Minneapolis, Minn)
      in the innominate artery.

PMID- 29349360
TI  - ULTRASOUND INDUCED MICROBUBBLE CAVITATION FOR THE TREATMENT OF CATHETERIZATION
      INDUCED VASOSPASM.

PMID- 29349362
TI  - Bridging stent repair of type III endoleak causing aortocaval fistula after
      branched aortic endovascular repair.
AB  - A 62-year-old man presented to our department with abdominal pain and diarrhea
      for 3 weeks on a background of previous branched endovascular repair for a
      thoracoabdominal aneurysm. A triple-phase computed tomography scan of his abdomen
      and pelvis showed a large aortocaval fistula caused by a type III endoleak from a
      dislodged superior mesenteric artery stent. He was successfully treated with a
      BeGraft (Bentley Innomed, Hechingen, Germany) by using an endovascular technique.

PMID- 29349363
TI  - A novel technique combining laparoscopic and endovascular approaches using image
      fusion guidance for anterior embolization of type II endoleak.
AB  - Type II endoleak (T2E) leading to aneurysm sac enlargement is one of the
      challenging complications associated with endovascular aneurysm repair. Recent
      guidelines recommend embolization of T2E associated with aneurysmal sac
      enlargement. Various percutaneous and endovascular techniques have been reported
      for embolization of T2E. We report a novel technique for T2E embolization
      combining laparoscopic and endovascular approaches using preoperative image
      fusion. We believe our technique provides a more direct access to the lumbar
      feeding vessels that is typically challenging with transarterial or translumbar
      embolization techniques.

PMID- 29349364
TI  - Endovascular repair of a thoracic aortic transection 31 years after blunt trauma.

PMID- 29349365
TI  - Debridement of atheroma in the proximal clamp site under hypothermic circulatory
      arrest for repair of abdominal aortic aneurysm with severe atherosclerosis.
AB  - Postoperative renal and other ischemic complications due to atheroembolization
      after clamping of the proximal site of an abdominal aortic aneurysm are
      catastrophic. We present here a method of debridement of atheroma and clamping
      under hypothermic circulatory arrest to avoid iatrogenic atheroembolization.

PMID- 29349366
TI  - An 18-cm unruptured abdominal aortic aneurysm.
AB  - Abdominal aortic aneurysm (AAA) is a significant source of morbidity and ranked
      by the Centers for Disease Control and Prevention as the 15th leading cause of
      death among adults aged 60 to 64 years. Size confers the largest risk factor for
      aneurysm rupture, with aneurysms >6 cm having an annual rupture risk of 14.1%. We
      present the case of a 60-year-old man found on ultrasound imaging at a health
      fair screening to have a 15-cm AAA. Follow-up computed tomography angiography
      revealed an 18-cm * 10-cm unruptured, infrarenal, fusiform AAA. Giant AAAs,
      defined as >11 cm, are rarely described in the literature. Our patient underwent
      successful transperitoneal AAA repair with inferior mesenteric artery
      reimplantation and was discharged home on operative day 6. We believe this case
      represents one of the largest unruptured AAAs in the literature and demonstrates
      the feasible approach for successful repair.

PMID- 29349367
TI  - A rare anatomic variant of a single-conduit supraclavicular cephalic arch
      draining into the external jugular vein presenting with recurrent arteriovenous
      fistula stenosis in a hemodialysis patient.
AB  - The cephalic arch is a common location of stenosis, especially in brachiocephalic
      fistulas. The cephalic arch has a number of anatomic variations. Cephalic arch
      stenoses are often resistant and have poor primary patency. Here we describe an
      unusual case of a hemodialysis patient with a single-conduit supraclavicular
      cephalic arch draining into the external jugular vein presenting with recurrent
      cephalic arch stenoses and external jugular vein stenosis. In our view, extrinsic
      compression by the clavicle may contribute to the high rate of recurrence, the
      lack of complete dilation of even high-pressure balloons, and a theoretically
      heightened risk of rupture when cutting balloons are used.

PMID- 29349368
TI  - Severe generalized dermatitis in a nickel-allergic patient with a popliteal
      artery nitinol stent.
AB  - We present the case of a patient who developed a full-body desquamating macular
      papular, pruritic rash after endovascular placement of a popliteal artery nitinol
      stent for acute limb ischemia. The rash was resistant to high-dose steroid and
      immunosuppressive treatment and intensive topical treatment. Patch testing
      revealed nickel allergy. The stented arterial segment was removed, with
      significant improvement in his symptoms that allowed the cessation of prednisone
      and topical treatments. The epidemiology, pathophysiology, and clinical effect of
      nickel allergy are discussed in addition to the use of nickel-alloy stents.

PMID- 29349369
TI  - Potentially stress-induced acute splanchnic segmental arterial mediolysis with a
      favorable spontaneous outcome.
AB  - A 62-year-old woman presented with hemithoracic anesthesia and acute abdominal
      pain following a violent psychological stress. Magnetic resonance imaging showed
      a thoracic hematoma with arachnoiditis of the spinal cord. Tomography revealed a
      typical aspect of segmental arterial mediolysis with multiple aneurysms and
      stenoses of the splanchnic arteries, confirmed by abdominal arteriography. There
      was no argument for hereditary, traumatic, atherosclerotic, infectious, or
      inflammatory arterial disease. Segmental arterial mediolysis was diagnosed on the
      basis of the radiologic data and probably involved both medullary and splanchnic
      arteries. The patient spontaneously recovered and was in good health 18 months
      later.

PMID- 29349370
TI  - Endovascular treatment with flow-diverting stents of symptomatic superior
      mesenteric artery after dissection aneurysm.
AB  - Isolated and spontaneous superior mesenteric artery dissection is a rare cause of
      acute abdominal pain. Whereas there is widespread consensus on conservative
      treatment of asymptomatic forms, revascularization would seem indicated in
      symptomatic complicated cases. A 73-year-old man presented with worsening
      epigastric pain. A computed tomography scan revealed an isolated and spontaneous
      superior mesenteric artery dissection with aneurysmal evolution of the false
      lumen, involving multiple side branches. The postdissection aneurysm was treated
      by endovascular exclusion with flow-diverting stents. The abdominal pain was
      completely relieved, and the patient remained asymptomatic at follow-up.

PMID- 29349371
TI  - External ventricular drain as a nontraumatic suction device in carotid
      endarterectomy.
AB  - Carotid endarterectomy is a commonly performed operation to remove plaque at the
      region of the carotid bifurcation. We present our technique to keep the field
      clear and to minimize potential trauma to the carotid using a neurosurgical
      external ventricular drain passed behind the common carotid and placed in the
      dependent position under the arteriotomy.

PMID- 29349372
TI  - Successful off-label use of the GORE EXCLUDER Iliac Branch Endoprosthesis to
      preserve gluteal perfusion during staged endovascular repair of bilateral
      isolated hypogastric aneurysms.
AB  - Endovascular repair of iliac artery aneurysms has emerged as an alternative to
      traditional open surgical repair. Although there is little consensus on
      indications to preserve hypogastric blood flow during aneurysm repair, it is well
      understood that complications from bilateral hypogastric occlusion may be
      significant. The GORE EXCLUDER Iliac Branch Endoprosthesis (W. L. Gore and
      Associates, Flagstaff, Ariz) received United States Food and Drug Administration
      approval in March 2016 for treatment of common iliac artery and aortoiliac
      aneurysms. This case report discusses an off-label use of GORE EXCLUDER Iliac
      Branch Endoprosthesis to maintain pelvic perfusion during treatment of bilateral
      internal iliac artery aneurysms without surrounding aortoiliac pathology.

PMID- 29349373
TI  - Lower extremity compartment syndrome after elective percutaneous fenestrated
      endovascular repair of an abdominal aortic aneurysm.
AB  - Ischemic complications after fenestrated endovascular aortic aneurysm repair
      (FEVAR) can result in significant morbidity and mortality. We present a case of a
      65-year-old man who underwent a FEVAR complicated by bilateral lower extremity
      compartment syndrome requiring four-compartment fasciotomies. This ischemic
      complication was likely caused by sheath occlusion because the patient had no
      evidence of arterial injury or distal plaque embolization. This case highlights
      the importance of careful postoperative monitoring after FEVAR, because the
      larger sheaths required can be occlusive and result in lower extremity ischemia,
      even for relatively short cases.

PMID- 29349374
TI  - Utilization of arterial grafts in foot replantation.
AB  - Our subject is a 36-year-old man who presented to the emergency department with
      bilateral lower extremity amputation at the level of the distal third of the
      tibia after a car accident. Surgery was planned for below-knee amputation of the
      right lower extremity and replantation of the left foot. The arteries dissected
      from the iatrogenically amputated segment were used as grafts to repair vascular
      gaps during the replantation. The patient's follow-up had been problem free. We
      concluded that whenever possible, amputated parts unsuitable for replantation
      should be examined thoroughly and neurovascular structures that might be used as
      grafts should be preserved.

PMID- 29349375
TI  - The use of bovine pericardial patch for vascular reconstruction in infected
      fields for transplant recipients.
AB  - Infectious vascular complications affecting transplant recipients may lead to
      severe morbidity and graft loss. This is a retrospective review of vascular
      repair with bovine pericardial patch (BPP) in infected fields for
      immunosuppressed patients. BPP was used as either a patch or an interposition
      graft. Five cases of arterial reconstruction in infected fields using BPP were
      performed. There were no complications related to bleeding, thrombosis, or
      recurrent infection. In our limited experience, the use of BPP as a vascular
      patch is successful, and it represents an alternative when vascular
      reconstruction is needed in the context of infected fields.

PMID- 29349376
TI  - Directional tip control technique for optimal stent graft alignment in angulated
      proximal aortic landing zones.
AB  - Angulated anatomy in the aorta, such as tortuous infrarenal aortic necks or steep
      aortic arches, is a significant challenge for endovascular aortic repair because
      it often causes inadequate sealing and fixation, which may lead to treatment
      failure. We have developed a technique using off-the-shelf equipment to precisely
      control the deployment of stent grafts in challenging landing zones. The key of
      this technique is to create a through-and-through wire between two access sites
      and to use a guiding device over the wire. This technique is best used with stent
      grafts without nose cones. We present an endovascular aneurysm repair case and a
      thoracic endovascular aortic repair case with challenging proximal landing zones
      treated by this technique. In both cases, technical success was attained, and
      follow-up imaging demonstrated well-aligned stent grafts. Our directional tip
      control technique is easy and effective. It can be a good technical solution for
      endovascular aortic treatment in angulated anatomy.

PMID- 29349377
TI  - Emergency thoracic endovascular aortic repair with celiac artery coverage in
      hereditary hemorrhagic telangiectasia.
AB  - Celiac artery (CA) coverage during thoracic endovascular aortic repair has been
      demonstrated to be a feasible and effective strategy for selected cases. However,
      there is a potential risk of ischemic complications due to CA coverage in
      patients with certain types of hereditary hemorrhagic telangiectasia (HHT).
      Herein, we report a case of thoracoabdominal aortic rupture in a patient with HHT
      that was successfully treated with emergency thoracic endovascular aortic repair
      covering the CA preceded by hepatic artery bypass. We also review the hepatic
      circulatory derangements and unique considerations in the surgical management of
      HHT.

PMID- 29349378
TI  - Hand-arm vibration syndrome: A rarely seen diagnosis.
AB  - Hand-arm vibration syndrome (HAVS) is a collection of sensory, vascular, and
      musculoskeletal symptoms caused by repetitive trauma from vibration. This case
      report demonstrates how to diagnose HAVS on the basis of history, physical
      examination, and vascular imaging and its treatment options. A 41-year-old man
      who regularly used vibrating tools presented with nonhealing wounds on his right
      thumb and third digit. Arteriography revealed occlusions of multiple arteries in
      his hand with formation of collaterals. We diagnosed HAVS, and his wounds healed
      after several weeks with appropriate treatment. HAVS is a debilitating condition
      with often irreversible vascular damage, requiring early diagnosis and treatment.

PMID- 29349379
TI  - Common femoral vein stent placement in a frozen abdomen causing acute limb
      ischemia.
AB  - A 73-year-old woman was admitted for left groin bleeding through an open wound
      near a fungating left inguinal mass from advanced anal carcinoma. The
      interventional radiology service placed left iliac vein and common femoral vein
      stents as there was concern for communication and involvement of the left common
      femoral vein with the open wound, contributing to groin hemorrhage. After the
      procedure, the patient developed limb ischemia related to mass effect of the
      stent on the left common femoral vein stent artery. She was revascularized by
      placement of a left common femoral vein stent artery stent. This report describes
      a viable option for revascularization in the rare occurrence of limb ischemia
      related to venous stenting.

PMID- 29349380
TI  - Type IV popliteal arterial entrapment associated with an osteochondroma.
AB  - Popliteal artery entrapment syndrome is a rare cause of peripheral vascular
      disease, often affecting young adults. Multiple studies have shown that
      osteochondromas can cause vascular injury. Intermittent compression,
      pseudoaneurysm, thrombosis, distal embolism, and venous thrombosis have all been
      described as possible complications. Here we present a case of popliteal arterial
      entrapment type IV with an associated tibial osteochondroma.

PMID- 29349381
TI  - Acute infection of Viabahn stent graft in the popliteal artery.
AB  - Peripheral stents are increasingly used for treatment of peripheral arterial
      disease, yet all implanted devices are potentially at risk for infection. We
      describe a 51-year-old man who underwent stenting in the femoropopliteal artery
      and presented 3 days later with leg pain, fever, and evidence of peripheral
      stigmata of embolization. Blood cultures grew methicillin-resistant
      Staphylococcus aureus and remained persistently positive despite antibiotic
      therapy. At surgical exploration, the popliteal artery had essentially been
      disintegrated by the infection, with only visible stent graft maintaining
      arterial continuity. Acute stent graft infections are rare and must be managed
      promptly to reduce morbidity.

PMID- 29349382
TI  - Intravascular ultrasound as a novel tool for the diagnosis and targeted treatment
      of functional popliteal artery entrapment syndrome.
AB  - Functional popliteal artery entrapment syndrome can be difficult to diagnose, as
      the imaging modalities presently employed are designed to detect anatomic
      entrapment. We describe a novel imaging technique to aid in diagnosis in this
      cohort. A 22-year-old cyclist presented with exercise-limiting claudication.
      Magnetic resonance angiography with provocative maneuvers was nondiagnostic.
      Digital subtraction angiography revealed long-segment occlusion of the popliteal
      artery with plantar flexion; however, the specific site of compression remained
      unclear. Intravascular ultrasound allowed specific localization of compression
      and further confirmed the diagnosis. Thus, we report this as an adjunctive
      imaging modality to definitively diagnose functional popliteal artery entrapment
      syndrome and to assist in operative planning.

PMID- 29349383
TI  - Endovascular extraction of a migrated large self-expanding laser-cut renal venous
      stent from the right ventricle.
AB  - Endovascular stent placement for decompression of an entrapped left renal vein
      (LRV) between the aorta and superior mesenteric artery is an alternative to
      surgical decompression for treating the nutcracker syndrome. However, an
      interventional approach may be challenging because of the unfavorable
      configuration of the LRV, leading to insufficient stent anchoring. We provide a
      case of a life-threatening stent migration from the LRV into the right ventricle
      2 days after stent placement and its endovascular retrieval.

PMID- 29349384
TI  - Acute hemifacial ischemia as a late complication of carotid stenting.
AB  - Concerns about carotid artery stenting (CAS) center primarily on procedural
      complications like acute occlusion, stroke, and long-term intrastent restenosis.
      External carotid artery (ECA) thrombosis is observed during CAS follow-up, but it
      often remains asymptomatic or, at worst, results in jaw claudication. We report
      here a case of late occlusion of the ECA after CAS with symptoms of acute
      homolateral facial ischemia as well as pain, cyanosis, tongue numbness, and skin
      coldness. The patient was submitted to local thrombolysis and balloon angioplasty
      with regression of symptoms after recanalization. With this report, we add a
      caveat about blockage of the ECA ostium during CAS.

PMID- 29349385
TI  - Novel, non-gadolinium-enhanced magnetic resonance imaging technique of pedal
      artery aneurysms.
AB  - Non-gadolinium-enhanced magnetic resonance angiography (nMRA) is a noninvasive,
      contrast-free imaging modality used for visualizing pedal arterial anatomy. We
      report application of the nMRA technique for detailed arterial imaging in a
      patient with dorsalis pedis aneurysm. Compared with digital subtraction
      angiography, we demonstrate that nMRA provides sufficient arterial detail needed
      to develop a complex operative plan before vascular intervention without risk of
      contrast agent or ionizing radiation exposure.

PMID- 29349386
TI  - Successful use of retrograde branched extension limb assembling technique in
      endovascular repair of pararenal abdominal aortic aneurysm.
AB  - Surgeon-modified retrograde branched extension limb assembling technique and
      bridged endografts were successfully used to exclude an asymptomatic pararenal
      abdominal aortic aneurysm and to reconstruct the superior mesenteric artery and
      bilateral renal arteries in a case with high-grade celiac artery stenosis,
      nondilated aorta above the superior mesenteric artery, and large lumen below the
      renal arteries. In patient-specific models for hemodynamics analysis, enhanced
      flow diversion to visceral arteries up to 6-month follow-up confirmed treatment
      feasibility; however, endograft configurations could be improved to avoid sharp
      corners at bifurcations, thereby ensuring smooth flow transport and possibly
      reducing risk for endograft narrowing or the development of thrombosis.

PMID- 29349387
TI  - Regarding "Endograft limb trimming and resheathing can be an alternative for
      emergent aortic repair without adequate stent graft availability".

PMID- 29349388
TI  - Atypical infrarenal aortic coarctation.

PMID- 29349389
TI  - Reply.

PMID- 29349390
TI  - Durability of the Viabahn stent graft after axillary artery pseudoaneurysm
      exclusion.
AB  - Pseudoaneurysm formation caused by iatrogenic arterial injury during a regional
      anesthetic block is a rare complication. We report a case of a 56-year-old male
      patient who developed an axillary artery pseudoaneurysm caused by brachial plexus
      block performed for an upper extremity dialysis access operation. Successful
      repair of this pseudoaneurysm was achieved with endovascular stent graft
      exclusion. The repaired axillary artery with the stent graft remained patent
      after 10 years of follow-up. The successful long-term patency of this treatment
      and a strategy to potentially avoid this complication are discussed.

PMID- 29349391
TI  - Inguinal pain and fullness due to an intravascular leiomyoma in the external
      iliac vein.
AB  - Intravascular leiomyomatosis (IVL) is a benign smooth muscle tumor that evolves
      from the pelvic veins and can spread to the central veins and heart. Cardiac
      involvement is the most commonly reported presentation. Initial diagnosis is
      difficult, and IVL is commonly misdiagnosed as thrombus or atrial myxoma.
      Appropriate imaging and a high clinical suspicion are required for accurate
      diagnosis. We report a rare case of IVL in the external iliac vein that recurred
      4 years after hysterectomy. Only four cases have been reported in the literature
      to involve the external iliac vein as it has no direct connection to pelvic
      venous drainage.

PMID- 29349392
TI  - Ovarian hyperstimulation syndrome as a rare cause of acute bilateral limb and
      renal ischemia.
AB  - Ovarian hyperstimulation syndrome (OHS) is a rare and potentially fatal
      condition, particularly when it is associated with arterial thromboembolic
      events. We present a case of acute ischemia of both lower limbs and left kidney
      due to OHS. The clinical presentation included voluminous ascites, pleural
      effusion, and significant ovarian enlargement. Subsequently, bilateral severe
      acute limb ischemia and left kidney segmental infarction were established.
      Surgical thromboembolectomy and muscle debridement of the lower limbs were
      necessary, and the patient recovered with partial limitations. A high index of
      suspicion and timely treatment are essential to minimize consequences of arterial
      thrombosis associated with OHS.

PMID- 29349393
TI  - Posterior tibial artery aneurysm in a child with SMAD3 mutation.
AB  - Peripheral arterial aneurysms in children are uncommon. We report a 6-year-old
      boy who developed a right posterior tibial artery aneurysm with symptoms
      including pain and pulsatile tenderness. His genetic testing revealed a SMAD3
      mutation, a condition associated with familial aortic aneurysm, early-onset of
      osteoarthritis, and peripheral aneurysms. The posterior tibial artery aneurysm
      was treated with surgical resection and primary anastomosis. The patient remained
      free of symptoms or aneurysm recurrence in his tibial artery 2 years later. This
      represents the first reported case of pediatric tibial artery aneurysm linked to
      a SMAD3 mutation.

PMID- 29349394
TI  - Infrared thermography in the diagnosis and management of vasculitis.
AB  - Vasculitis is a clinical condition with associated diagnostic challenges due to
      nonspecific symptoms and lack of a confirmatory imaging modality. We report a
      case of a 39-year-old female patient who developed generalized malaise, lethargy,
      and headache. Laboratory evaluation showed elevated inflammatory markers.
      Conventional imaging studies including computed tomography and carotid duplex
      ultrasound were unremarkable. Infrared thermography revealed enhanced
      thermographic signals in the left carotid artery and aortic arch. Corticosteroid
      therapy was commenced, and the patient responded well. Follow-up infrared
      thermography at 6 months showed complete resolution of the thermographic pattern,
      and the patient remained symptom free.

PMID- 29349395
TI  - Delayed migration of a thrombosed aortic endograft within a thrombosed aneurysm
      sac resulting in continued sac expansion and rupture.
AB  - We present the case of delayed migration of a thrombosed aortic endograft within
      a thrombosed aneurysm sac that expanded and ruptured. Dilation of the aortic neck
      likely led to endograft migration and exposure of the occluded endograft and
      aneurysm sac to systemic pressure. Although no endoleak was identified, a key
      finding on ultrasound showed mobility of the sac thrombus. This may be an
      indicator of flow within the sac that may predict potential for rupture. Despite
      thrombosis of the aortic sac and endograft, the risk of rupture still lingers,
      and thus continued surveillance of occluded endografts may be prudent.

PMID- 29349396
TI  - Isolated lower extremity vasculitis leading to progressive critical limb
      ischemia.
AB  - Giant cell arteritis is a large- and medium-vessel vasculitis that has been
      described as a systemic disease process with disseminated vessel involvement.
      Advances in vascular imaging techniques have demonstrated that involvement of the
      large vessels of the upper and lower limbs may be more prevalent than was once
      thought, although the clinical implications of this are unknown. Isolated lower
      extremity claudication without systemic or classic cranial symptoms, especially
      as a primary manifestation of giant cell arteritis, is rare. We present the case
      of a patient with isolated bilateral limb claudication that rapidly progressed to
      critical limb ischemia requiring urgent surgical intervention after steroid
      therapy. Our patient has consented to the publication of this report.

PMID- 29349397
TI  - Femoral artery embolization of a thoracic stray bullet.
AB  - Arterial bullet embolization after a thoracic gunshot wound represents a
      diagnostic and therapeutic challenge. The absence of an apparent exit wound
      should alert the clinician. Cardiac bullet injuries are mostly fatal. However, in
      some cases, patients may remain stable, and conservative management can be an
      acceptable strategy. We present a case report of a 7.62- * 39-mm thoracic stray
      bullet that embolized to the femoral artery.

PMID- 29349398
TI  - Unexplained rupture after endovascular aneurysm repair.
AB  - We present a case of a 70-year-old man who was admitted with rupture of an
      abdominal aneurysm 4 years after endovascular aneurysm repair. He was compliant
      with yearly follow-up computed tomography angiography. One month earlier, his
      computed tomography angiogram showed perfect exclusion of the aneurysm and no
      endoleak. We explanted the stent graft and confirmed effective sealing, and the
      graft was intact. We found no signs of infection during 2 years of follow-up.
      This rupture is nonpredictable and unexplained and illustrates that unremarkable
      imaging does not guarantee prevention of rupture. This case shows that the
      ultimate failure of endovascular aneurysm repair cannot be prevented despite
      surveillance protocols.

PMID- 29349399
TI  - Subclavian steal syndrome without subclavian stenosis.
AB  - Subclavian steal syndrome (SSS) has been well described in the setting of
      subclavian stenosis. We describe an unusual case of SSS caused by a high-flow
      arteriovenous dialysis fistula in the absence of subclavian stenosis, provide a
      review of the literature, and propose that arteriovenous fistula-induced SSS is
      an underdiagnosed cause of syncope in this population of patients.

PMID- 29349400
TI  - Single-session total endovascular iliocaval reconstruction with stent grafting
      for the treatment of inferior vena cava agenesis and concurrent iliac venous
      aneurysm rupture.
AB  - Iliac venous aneurysms are rare vascular abnormalities that may be manifested by
      abdominal masses, pelvic tenderness, or hypovolemia and may lead to rupture,
      thrombosis, pulmonary embolism, paradoxical embolism, or death. Inferior vena
      cava agenesis, like venous aneurysm, is an uncommon condition that may present
      with deep venous thrombosis. This report describes a patient with inferior vena
      cava agenesis and iliac venous aneurysm rupture treated with emergent iliocaval
      reconstruction and endovascular stent graft placement.

PMID- 29349401
TI  - Staged reconstruction of the inferior vena cava after gunshot injury.
AB  - A 23-year-old man with a gunshot injury to the abdomen and cardiac arrest
      requiring emergency department thoracotomy had a transection of the distal
      inferior vena cava (IVC) and small bowel injury. Because of persistent
      hemorrhagic shock, the IVC was ligated. During the next 3 days, he developed
      worsening bilateral leg edema. He was taken back for reanastomosis of his small
      bowel and reconstruction of the IVC using autologous femoral vein harvested from
      the right leg. We think that patients requiring ligation of the vena cava with
      worsening leg edema can benefit from a staged reconstruction of the IVC.

PMID- 29349402
TI  - Transposition of the persistent sciatic artery for lower limb revascularization
      after resection of an embolizing proximal sciatic artery aneurysm.
AB  - We present a novel surgical technique for lower limb revascularization after
      resection of an aneurysm of the persistent sciatic artery that had led to
      recurrent peripheral embolization and severe ischemia. The superficial femoral
      artery in this patient was hypoplastic, and the sciatic artery continued into the
      popliteal artery as the source of blood supply to the lower leg. For
      revascularization, we used the distally pedicled healthy two-thirds of the
      persistent sciatic artery, transposed it from its posterior position to a nearly
      anatomic anteromedial position, and anastomosed it to the proximal superficial
      femoral artery.

PMID- 29349403
TI  - A novel hybrid left renal vein transposition and endovascular stenting technique
      for the treatment of posterior nutcracker syndrome.
AB  - Posterior nutcracker syndrome occurs when a retroaortic left renal vein becomes
      compressed between the abdominal aorta and the lumbar spine. Although open
      surgical approaches remain the treatment of choice, endovascular stenting has
      been used successfully. We describe a case of a 28-year-old man who presented
      with microscopic hematuria, left-sided flank pain, and testicular swelling.
      Computed tomography findings were consistent with posterior nutcracker syndrome.
      He underwent a novel hybrid operation that included left renal vein transposition
      followed by endovascular stenting. Repeated imaging at 3 and 12 months revealed a
      patent stent with complete resolution of symptoms.

PMID- 29349404
TI  - External jugular vein thrombosis secondary to deep tissue neck massage.
AB  - An 85-year-old man presented with an acute asymptomatic lateral neck mass in the
      context of deep tissue neck massages during the past year. He was referred to
      vascular surgery after an ultrasound examination of the neck revealed a thrombus
      in the external jugular vein. His past medical history and comorbidities were
      noncontributory. A multidisciplinary team of vascular surgeons and hematologists
      did not recommend any anticoagulation, given that the patient did not have any
      risk factors for thrombosis as well as normal D-dimer levels. The patient was
      maintained on his previous dose of aspirin (81 mg daily).

PMID- 29349405
TI  - Pseudoaneurysm of the external iliac artery is a rare late complication after
      total hip arthroplasty.
AB  - Vascular injury as a delayed complication of total hip arthroplasty (THA) is
      rare. We present a case of pseudoaneurysm of the external iliac artery due to
      chronic irritation from a prominent bone spicule occurring 2 years after revision
      THA. We successfully managed the patient with open repair, and there has been no
      sign of recurrence in the 2 years since the previous surgery. This report
      suggests that patients who have undergone THA should be followed up carefully and
      assessed for vascular injuries even after a substantial time.

PMID- 29349406
TI  - Thrombolytic therapy for critical limb ischemia in a Jehovah's Witness with
      severe anemia.
AB  - A patient's refusal to receive blood products can pose both clinical and ethical
      challenges to the surgeon. In this report, we review the case of a Jehovah's
      Witness presenting with critical lower limb ischemia and severe anemia for whom
      the decision of whether to perform thrombolytic therapy was complicated by his
      refusal to accept blood products. The case demonstrates that thrombolytic therapy
      can produce favorable results in severely anemic patients even when transfusion
      is not an option. We conclude that offering thrombolytic therapy in this context
      is a reasonable therapeutic option from both a clinical and ethical perspective.

PMID- 29349407
TI  - Endovascular recanalization of occluded superior mesenteric artery using
      retrograde access through the inferior mesenteric artery.
AB  - Symptomatic occlusion of the superior mesenteric artery can be treated by open
      repair, hybrid procedure, or endovascular revascularization. In most cases,
      endovascular procedures are done by the antegrade approach. We report a case of a
      67-year-old woman who presented with acute-on-chronic mesenteric ischemia
      successfully treated by retrograde endovascular recanalization of an occluded
      common hepatomesenteric trunk through the inferior mesenteric artery and arc of
      Riolan.

PMID- 29349408
TI  - Infolding of fenestrated endovascular stent graft.
AB  - We report a case of infolding of a fenestrated stent graft involving the visceral
      vessel segment after a juxtarenal abdominal aorta aneurysm repair. The patient
      remains free of any significant endoleak, and the aortic sac has shown
      regression. The patient remains asymptomatic, with no abdominal pain, with normal
      renal function, and without ischemic limb complications. We hypothesize that
      significant graft oversizing (20%-30%) with asymmetric engineering of the
      diameter-reducing ties may have contributed to the infolding. Because of the
      patient's asymptomatic nature and general medical comorbidities, further
      intervention was deemed inappropriate as the aneurysmal sac is regressing despite
      the infolding.

PMID- 29349409
TI  - Salvage of bilateral renal artery occlusion after endovascular aneurysm repair
      with open splenorenal bypass.
AB  - We report renal salvage maneuvers after accidental bilateral renal artery
      coverage during endovascular aneurysm repair of an infrarenal abdominal aortic
      aneurysm. A 79-year-old man with an infrarenal abdominal aortic aneurysm was
      treated with endovascular aneurysm repair. Completion angiography demonstrated
      coverage of the renal arteries. Several revascularization techniques were
      attempted, including endograft repositioning and endovascular stenting through
      the femoral and brachial approach. The patient eventually underwent open
      splenorenal bypass with a Y Gore-Tex graft (W. L. Gore & Associates, Flagstaff,
      Ariz). After 3 months, computed tomography showed no evidence of endoleak and
      patent renal arteries. Renal function was well maintained, and the patient did
      not require dialysis.

PMID- 29349410
TI  - Rupture of abdominal aortic aneurysm between early and late phases of enhanced
      computed tomography.

PMID- 29349411
TI  - Takayasu arteritis with middle aortic syndrome and mesenteric ischemia treated by
      aortic stenting.
AB  - A 48-year-old woman suffering from Takayasu arteritis presented with middle
      aortic syndrome consisting of abdominal pain, refractory hypertension with
      pulmonary edema and pleural effusions, and lower limb ischemia. She failed to
      improve with high-dose steroid therapy and underwent endovascular stenting of two
      severe stenoses in the supraceliac and infrarenal aorta. Her symptoms resolved
      and hypertension improved after the procedure.

PMID- 29349412
TI  - Treatment of a symptomatic intrathoracic internal carotid artery.
AB  - Intrathoracic common carotid artery bifurcations are an anatomic anomaly with
      such rarity that only six cases have been reported to date. The true incidence of
      and preferred treatment options for a diseased intrathoracic common carotid
      artery bifurcation or internal carotid artery (ICA) have not been clearly
      described. This case report describes a 72-year-old man who experienced a
      postoperative right hemispheric stoke after an aortic valve replacement,
      radiofrequency maze procedure, and left atrial appendage clip. Postoperative
      cerebrovascular evaluation revealed a severely diseased intrathoracic ICA that
      was treated by ligation of the diseased proximal ICA and transposition of the
      distal ICA to the disease-free external carotid artery. The patient provided
      written consent to present the history, data, and images in this manuscript.

PMID- 29349413
TI  - Safety and efficacy of a modified HeRO dialysis device in achieving early graft
      cannulation: A single-institution experience.
AB  - Hemodialysis Reliable Outflow (HeRO) grafts (Merit Medical Systems, Inc, South
      Jordan, Utah) provide a means for access in catheter-dependent hemodialysis
      patients but typically require several weeks for tissue incorporation. Modifying
      the HeRO graft with an ACUSEAL graft (W. L. Gore & Associates, Newark, Del) can
      allow immediate cannulation, thus reducing catheter dependence time and its
      associated complications. A retrospective review of patients at our institution
      from 2013 to 2016 who underwent placement of a modified HeRO dialysis system with
      ACUSEAL graft was performed. Complications and outcomes were analyzed, with
      patency rates and hours to successful cannulation being major end points.
      Modified HeRO grafts were successfully placed in 10 catheter-dependent patients.
      Postoperative complications included two thromboses and one hematoma. At 6 months
      of follow-up, mean time to graft cannulation was 33.7 hours, with 100% success;
      the primary and secondary patency rates were 70% and 90%, respectively. Our
      modification allows an accelerated use of the HeRO system, reducing catheter
      dependence time with acceptable postoperative complications and patency rates.

PMID- 29349414
TI  - Idiopathic radial artery true aneurysm.

PMID- 29349415
TI  - A track made by organized thrombus after catheter fragment removal mimicking a
      remnant catheter in the popliteal artery.

PMID- 29349416
TI  - Acute aortic occlusion secondary to aortic endograft migration and collapse.

PMID- 29349417
TI  - Emergent endovascular repair of a ruptured giant internal iliac artery aneurysm
      using an inverted iliac limb endograft.

PMID- 29349418
TI  - Femoral artery embolism of bullet after thoracic gunshot wound.

PMID- 29349419
TI  - Covered endovascular repair of the paravisceral aorta.
AB  - Open aortic repair is considered the "gold standard" treatment for aortic
      occlusive disease. We present the case of an 83-year-old patient with refractory
      hypertension caused by paravisceral aortic stenosis including both renal arteries
      and the superior mesenteric artery. We planned an endovascular approach and
      treated the patient with parallel stent grafts in the paravisceral aorta. At 1.5
      years after the operation, the patient was free of hypertensive episodes. Covered
      endovascular repair of the paravisceral aorta may be a valuable alternative to
      open aortic repair in patients unfit for open surgery. More research is needed to
      evaluate the long-term effects of this technique.

PMID- 29349420
TI  - Common carotid artery pseudoaneurysm secondary to Mycobacterium tuberculosis
      treated with resection and reconstruction with saphenous vein graft.
AB  - Extracranial carotid artery aneurysms secondary to Mycobacterium tuberculosis
      infection are exceedingly rare. Despite an uncommon location and offending
      pathogen, the treatment paradigm follows that of all mycotic aneurysms. We report
      the case of a right common carotid artery pseudoaneurysm caused by a tuberculous
      infection, successfully treated with antibiotics, resection, and autologous
      interposition graft.

PMID- 29349421
TI  - Large-diameter inferior mesenteric artery in a case involving a ruptured common
      iliac artery aneurysm.

PMID- 29349422
TI  - Hybrid management of a ruptured right subclavian artery aneurysm dissection.
AB  - Aberrant right subclavian artery is the most common congenital malformation of
      the aortic arch (0.4%-2.0%). Aneurysms of aberrant subclavian arteries are
      extremely rare. This results in little experience with their treatment. We
      describe a case of a patient who presented to the emergency department with a
      dissection of an aberrant right subclavian artery that later progressed to
      rupture. Besides hemodynamic instability, this caused an acute superior vena cava
      syndrome, making airway control difficult. In the operating room, we obtained
      proximal control through thoracic endovascular aortic repair; median sternotomy
      was performed for distal control and evacuation of massive hemomediastinum.

PMID- 29349423
TI  - Ruptured giant popliteal artery aneurysm.

PMID- 29349424
TI  - Symptomatic giant carotid artery aneurysm.

PMID- 29349425
TI  - Assessment of lower extremity ischemia using smartphone thermographic imaging.
AB  - Conventional diagnostic modalities for assessing arterial circulation or tissue
      perfusion include blood pressure measurement, ultrasound evaluation, and contrast
      based angiographic assessment. An infrared thermal camera can detect infrared
      radiation energy from the human body, which generates a thermographic image to
      allow tissue perfusion analysis. We describe a smartphone-based miniature thermal
      imaging system that can be used as an adjunctive imaging modality to assess
      tissue perfusion. This smartphone-based camera device is noninvasive, simple to
      use, and cost-effective in assessing patients with lower extremity tissue
      perfusion. Assessment of patients with lower extremity arterial ischemia can be
      performed by a variety of diagnostic modalities, including ankle-brachial index,
      absolute systolic ankle or toe pressure, transcutaneous oximetry, arterial
      Doppler waveform, arterial duplex ultrasound, computed tomography scan, arterial
      angiography, and thermal imaging. We herein describe a noninvasive imaging
      modality using smartphone-based infrared thermography.

PMID- 29349427
TI  - An unusual cause of cruralgia.

PMID- 29349426
TI  - Development of a pulsatile, tissue-based, versatile vascular surgery simulation
      laboratory for resident training.
AB  - Simulation in surgery is becoming an important component of surgical education.
      Training on bench top models has been demonstrated to improve technical skills.
      The objective of our project was to create a vascular surgery simulation model.
      The simulation model consists of a platform, artificial blood reservoir,
      artificial blood, inflow and outflow limbs, electric motor, battery, pulse
      generator, and cryopreserved vessel. Three different vascular surgery simulation
      stations were created: carotid endarterectomy with shunting and patch
      angioplasty, arterial bypass, and arteriovenous graft formation. A scientific
      study involving surgical residents will need to be undertaken to determine
      whether this simulator has intermodal transferability.

PMID- 29349428
TI  - Hybrid repair of a large pseudoaneurysm of the proximal right subclavian artery
      in a Marfan patient.
AB  - A pseudoaneurysm of the proximal right subclavian artery is rare and most
      commonly caused by penetrating or blunt trauma. We report a case of a Marfan
      patient with a large iatrogenic pseudoaneurysm of the right subclavian artery,
      induced by a puncture lesion during central venous catheter placement for an
      elective endovascular thoracic aortic procedure. The patient was successfully
      treated with a hybrid approach, which consisted of endovascular coiling and
      balloon occlusion of the adjacent vessels, followed by open surgical exploration
      and uneventful closure of the puncture hole with the use of bovine pericardium
      reinforced sutures.

PMID- 29349429
TI  - Repair of a mycotic abdominal aortic aneurysm in a neonate using an everted
      jugular vein patch.
AB  - A 43-day-old boy presented with bacteremia after umbilical artery
      catheterization. Duplex ultrasound examination revealed a 1.1- * 1.6-cm mycotic
      infrarenal aortic aneurysm and an incidental asymptomatic occluded right common
      iliac artery. Resection and repair were completed by creating an everted, double
      layered internal jugular vein patch. Screening ultrasound examination 10 months
      postoperatively demonstrated successful repair.

PMID- 29349430
TI  - Surgical repair of a celiac artery aneurysm using a sutureless proximal
      anastomosis device.
AB  - Some celiac artery aneurysms are not suitable for endovascular therapy. We
      describe the case of a 63-year-old man with a celiac trunk aneurysm extending to
      the hepatosplenic bifurcation. The aneurysm was resected and oversewn at the
      origin from the abdominal aorta. A saphenous vein bypass from the supraceliac
      aorta to the celiac artery bifurcation was performed using a sutureless
      anastomotic device (PAS-Port system; Cardica, Redwood City, Calif) to create the
      proximal anastomosis, eliminating the need for aortic clamping. This system is
      thought to make direct proximal aortic anastomosis safe and easy in patients
      requiring surgical reconstruction of celiac artery aneurysms.

PMID- 29349431
TI  - Complete robotic repair of a renal artery aneurysm.
AB  - Although the majority of renal artery aneurysms require only observation, those
      that require treatment have been addressed primarily surgically or
      endovascularly. We report a case of surgical resection of a large, symptomatic
      renal artery aneurysm from an entirely robotic approach.

PMID- 29349432
TI  - Aortic arch banding procedure for proximal type I endoleak after thoracic
      endovascular aneurysm repair with the chimney technique.
AB  - An aortic arch banding procedure was performed on an 82-year-old man for
      treatment of proximal type I endoleaks 2 days after he had undergone emergency
      thoracic endovascular aortic repair with the chimney technique for a ruptured
      aortic arch aneurysm. Contrast-enhanced computed tomography after the second
      procedure demonstrated significant shrinkage of the aneurysmal sac as well as a
      complete disappearance of the endoleaks. The basic concept of this technique is
      to treat the type IA endoleak, including possible gutter endoleaks, by creating a
      new proximal seal zone distal to the chimney graft using a banding technique.

PMID- 29349433
TI  - Popliteal artery entrapment syndrome presenting as acute limb ischemia in
      pregnancy.
AB  - Popliteal artery entrapment syndrome typically causes calf claudication in young
      active adults. Acute limb ischemia from popliteal artery thrombosis,
      embolization, or aneurysmal degeneration is less common. Chronic compression,
      histologic changes, and predisposing factors, such as vigorous exercise or
      hypercoagulability, play a role in these cases. We present the case of a 32-year
      old pregnant woman with acute limb ischemia found to have popliteal artery
      thrombosis as a result of popliteal artery entrapment syndrome. Although many
      imaging modalities are available, pregnancy creates a unique situation in which
      consideration of irradiation and exposure to contrast material is important in
      diagnosis and treatment.

PMID- 29349434
TI  - A novel application of the culotte stent technique to bail out a jailed common
      iliac artery.
AB  - Implanting a self-expandable stent at the ostium of the common iliac artery (CIA)
      may lead to coverage of the orifice of the contralateral CIA. Here, we describe a
      novel application of the culotte stent technique using a balloon-expandable stent
      to bail out an ostial stenotic legion of a jailed CIA due to prior self
      expandable stent placement. The bilateral CIAs were revascularized by culotte
      stenting, and patency of the stents was confirmed 3 years after the procedure.
      The culotte stent technique was successfully applied to an ostial stenotic lesion
      of a jailed CIA.

PMID- 29349435
TI  - Emergency endovascular coiling of a ruptured giant splenic artery aneurysm.
AB  - Splenic artery aneurysms (SAAs) are the third most common abdominal aneurysm.
      Endovascular treatment of SAAs is preferred, and coiling is the most commonly
      used technique. Ruptured giant (>5 cm) SAAs are usually treated with open surgery
      including splenectomy. We present a rare case of a ruptured 15-cm giant SAA in an
      84-year-old woman treated successfully with emergency endovascular coiling. To
      our knowledge, this is one of the few reports of emergency endovascular treatment
      for ruptured giant SAA.

PMID- 29349436
TI  - Superficial temporal artery aneurysm associated with immunoglobulin G4-related
      disease.
AB  - A 68-year-old man was admitted because of a pulsatile mass and pain in the left
      temporal region, and computed tomography demonstrated the superficial temporal
      artery aneurysm. He underwent aneurysmectomy, and pathologic investigation
      revealed marked thickness of the adventitia with substantial plasmacyte
      infiltration. On immunoglobulin G4 (IgG4) immunohistochemistry, IgG4-positive
      lymphocytes were scattered in the adventitia, and biochemical tests revealed
      elevation of IgG4 (200 mg/dL). The case satisfied the criteria for both giant
      cell arteritis and IgG4-related disease (IgG4-RD). This case report suggested
      that IgG4-RD can occur in the superficial temporal artery and that IgG4-RD may
      partially overlap with a subtype of giant cell arteritis.

PMID- 29349437
TI  - Staged endovascular repair of an abdominal aortic aneurysm adjacent to a chronic
      high-flow iliocaval traumatic arteriovenous fistula.
AB  - Large-vessel chronic traumatic arteriovenous fistulas are a rare complication
      after trauma. Delayed presentation can consist of one or more features of high
      output cardiac failure, pulsatile abdominal mass, bruit, limb ischemia, and
      venous congestion. We describe a patient with a complex iliocaval fistula
      secondary to a remote gunshot wound associated with a large 8.5-cm aortic
      aneurysm. Informed consent of the patient was obtained for publication of the
      case.

PMID- 29349438
TI  - Idiopathic internal mammary artery aneurysm in the setting of aberrant right
      subclavian artery.
AB  - Aneurysms of the internal mammary artery are extremely rare. Immediate treatment
      is necessary because of the high risk of rupture that can be life-threatening.
      Here we describe a case of idiopathic internal mammary artery aneurysm in a 54
      year-old woman in the setting of aberrant right subclavian artery. The aneurysm
      was successfully treated with coil embolization without complications.

PMID- 29349439
TI  - Protein C deficiency resulting from two mutations in PROC presenting with
      recurrent venous thromboembolism.
AB  - Hereditary protein C (PC) deficiency is an autosomal dominant disorder associated
      with a high risk of venous thromboembolism (VTE). Here we report a case of
      inherited PC deficiency associated with recurrent deep venous thrombosis. Two
      mutations were revealed in PROC (c.1152C>G, p.N384K and c.1207G>T, p.G403W) by
      genetic testing. Results from this case suggest that the inherited PC deficiency
      due to the PROC mutations may cause recurrent VTE. Long-term anticoagulant
      therapy may be appropriate for these patients with recurrent VTE and hereditary
      PC deficiency.

PMID- 29349440
TI  - Preservation of internal iliac arteries during endovascular aneurysm repair using
      "eye of the tiger" technique.
AB  - Parallel endografts were introduced as a way to expand endovascular repair of
      aneurysms involving branch vessels. However, endoleaks as a result of the gutters
      between the parallel endografts made this technique less favorable. The "eye of
      the tiger" technique was introduced to reduce the gutters between the parallel
      endografts proximally in the aorta. We report endovascular repair of infrarenal
      abdominal aortic aneurysm using eye of the tiger technique distally to preserve
      the internal iliac arteries.

PMID- 29349441
TI  - Association between sn-2 fatty acid profiles of breast milk and development of
      the infant intestinal microbiome.
AB  - Increasing evidence shows that host diet and gut microbes are related. Previous
      studies have shown the effects of specific dietary fatty acids (FAs) on
      intestinal microbiota, but little is known about the effect of the
      stereospecifically numbered sn-2 position in triglycerides (TG) of human milk on
      the gut microbiome of infants. This study aimed at examining possible effects of
      sn-2 FAs of human milk on the gut microbial development of breastfeeding babies.
      Sn-2 FAs and intestinal microbiota were assessed by GC-MS and high-throughput 16S
      rRNA sequencing, respectively. The results showed that breast milk from mothers
      in China contained ten major sn-2 FAs dominated by palmitic acid (C16:0, 54.42%),
      oleic acid (C18:1 n-9, 14.95%), linoleic acid (LA, C18:2 n-6, 12.81%), myristic
      acid (C14:0, 4.50%) and C12:0 (3.17%). Total long chain unsaturated fatty acids
      (LCUFA) decreased from colostrum to mature milk, while total saturated fatty
      acids (SFA) showed no significant difference during lactation. A significant
      association between sn-2 FAs in milk and infant gut microbiota was found between
      decanoic acid (C10:0), myristic acid (C14:0), stearic acid (C18:0), C16:0,
      arachidonic acid (AA, C20:4 n-6), docosahexaenoic acid (DHA, C22:6 n-3) with
      Bacteroides, Enterobacteriaceae, Veillonella, Streptococcus, and Clostridium.
      These microbes were involved in short-chain fatty acid (SCFA) production and
      other functions, and significantly increased at 13-15 d after breastfeeding was
      initiated. C16:0 and DHA were relevant to most of the microbes. This study
      demonstrated the relatively steady profiles of sn-2 FAs in breast milk and gut
      microbiota of infants, together with their correlation during the breastfeeding
      period. The above results provided important information for designing the
      configuration of FAs in next-generation formulas for Chinese infants.

PMID- 29349442
TI  - Impact of Nb vacancies and p-type doping of the NbCoSn-NbCoSb half-Heusler
      thermoelectrics.
AB  - The half-Heuslers NbCoSn and NbCoSb have promising thermoelectric properties.
      Here, an investigation of the NbCo1+ySn1-zSbz (y = 0, 0.05; 0 <= z <= 1) solid
      solution is presented. In addition, the p-type doping of NbCoSn using Ti and Zr
      substitution is investigated. Rietveld analysis reveals the gradual creation of
      Nb vacancies to compensate for the n-type doping caused by the substitution of Sb
      in NbCoSn. This leads to a similar valence electron count (~18.25) for the
      NbCo1+ySn1-zSbz samples (z > 0). Mass fluctuation disorder due to the Nb
      vacancies strongly decreases the lattice thermal conductivity from 10 W m-1 K-1
      (z = 0) to 4.5 W m-1 K-1 (z = 0.5, 1). This is accompanied by a transition to
      degenerate semiconducting behaviour leading to large power factors, S2/rho = 2.5
      3 mW m-1 K-2 and figures of merit, ZT = 0.25-0.33 at 773 K. Ti and Zr can be used
      to achieve positive Seebeck values, e.g. S = +150 MUV K-1 for 20% Zr at 773 K.
      However, the electrical resistivity, rho323K = 27-35 mOmega cm, remains too large
      for these materials to be considered useful p-type materials.

PMID- 29349443
TI  - Large valley polarization in monolayer MoTe2 on a magnetic substrate.
AB  - On the basis of valley degree of freedom, there would be immense potential
      application in valleytronics. Introducing magnetism into triangular or hexagonal
      lattices is a promising route to realize valley polarization, which is
      indispensable for applying the valley degree of freedom. In this study, we
      explored valley polarization by depositing a heterostructure of a MoTe2 monolayer
      on the (0 0 1) surface of an antiferromagnetic RbMnCl3 substrate. First
      principles-calculations showed that due to proximity-induced Zeeman effects, the
      MoTe2 monolayer was drastically magnetized by the topmost Mn layer in the
      substrate and a very large valley splitting (about 109 meV) was achieved. Using
      an effective Hamiltonian model, the effect of the competition of the spin-orbit
      coupling (SOC) and exchange field in the system on the valley polarization was
      also investigated. The magnitude of the valley splitting was found to be limited
      by the smaller SOC value and the induced exchange field, providing information on
      the enhancement of the valley polarization. A device rudiment with an anomalous
      valley Hall effect is proposed.

PMID- 29349444
TI  - Non-invasive force measurement reveals the number of active kinesins on a
      synaptic vesicle precursor in axonal transport regulated by ARL-8.
AB  - Kinesin superfamily protein UNC-104, a member of the kinesin-3 family, transports
      synaptic vesicle precursors (SVPs). In this study, the number of active UNC-104
      molecules hauling a single SVP in axons in the worm Caenorhabditis elegans was
      counted by applying a newly developed non-invasive force measurement technique.
      The distribution of the force acting on a SVP transported by UNC-104 was spread
      out over several clusters, implying the presence of several force-producing units
      (FPUs). We then compared the number of FPUs in the wild-type worms with that in
      arl-8 gene-deletion mutant worms. ARL-8 is a SVP-bound arf-like small guanosine
      triphosphatase, and is known to promote unlocking of the autoinhibition of the
      motor, which is critical for avoiding unnecessary consumption of adenosine
      triphosphate when the motor does not bind to a SVP. There were fewer FPUs in the
      arl-8 mutant worms. This finding indicates that a lack of ARL-8 decreased the
      number of active UNC-104 motors, which then led to a decrease in the number of
      motors responsible for SVP transport.

PMID- 29349445
TI  - Discovery of novel diarylpyrimidines as potent HIV-1 NNRTIs by investigating the
      chemical space of a less explored "hydrophobic channel".
AB  - A new series of diarylpyrimidines (DAPYs) were designed, synthesized and
      evaluated as novel HIV-1 NNRTIs to further explore the chemical space surrounding
      the "hydrophobic channel" of the NNRTI binding pocket (NNIBP), guided by the
      comprehensive analysis of X-ray structural biology data of HIV-1 RT/NNRTI
      complexes and molecular modeling. Encouragingly, most of the synthesized DAPYs
      were found to be active against the HIV-1 wild-type (WT) strain with EC50 values
      ranging from 3 nM to 63 nM, and displayed significantly reduced cytotoxicity
      compared with etravirine (ETV) and rilpivirine (RPV). Among them, two most
      promising compounds Z10 (EC50 = 3 nM) and Z13 (EC50 = 3 nM) showed equivalent
      potency against the HIV-1 WT strain to the reference drugs efavirenz (EFV, EC50 =
      3 nM) and ETV (EC50 = 3 nM). Notably, Z13 also showed the most potent activity
      against HIV-1 mutant strains including K103N (EC50 = 10 nM), E138K (EC50 = 22 nM)
      and RES056 (EC50 = 0.935 MUM). Against mutant strains Y181C, Y188L and F227L +
      V106A, Z17 showed double-digit nanomolar inhibitory activity with EC50 values 27
      nM, 98 nM and 30 nM, respectively. The structure-activity relationships (SARs)
      and molecular docking studies provided important clues for further molecular
      elaboration. Collectively, this study provides useful information to guide lead
      optimization and drug discovery via the exploration of this seldom investigated
      region.

PMID- 29349446
TI  - Ameliorative role of camel whey protein and rosuvastatin on induced dyslipidemia
      in mice.
AB  - The incidence of obesity is rapidly increasing throughout the world. Dyslipidemia
      is a major risk factor for a number of chronic diseases, including diabetes and
      cardiovascular diseases. This work presents a novel approach to study the
      activity of camel whey protein (WP) with antioxidant and anti-inflammatory
      properties as a cheap dietary protein substance extracted from camel milk to
      produce satiety and help in building muscles. Mice model suffering from
      dyslipidemia as a result of feeding on high fat-cholesterol diet for 8 weeks were
      administrated with either camel WP and/or rosuvastatin for 4 weeks. Dyslipidemia
      revealed significant increase in anthropometrical measurements, levels of
      glucose, insulin, cholesterol, triglycerides, low-density lipoprotein, total
      leucocyte count, inflammatory cytokines and reactive oxygen species, accompanied
      by a significant elevation in activating transcription factor-3 and inducible
      nitric oxide synthase expressions. These alterations were correlated with a
      profound reduction in high-density lipoprotein, peroxisome proliferator-activated
      receptor alpha and adiponectin along with a decrease in liver and muscle
      mitochondrial proteins. Rosuvastatin treatment to mice suffering from
      dyslipidemia in combination with camel WP for 4 weeks ameliorated these
      parameters. Notably, animals treated with both camel WP and rosuvastatin
      exhibited a remarkable decrease in the incidence of dyslipidemia. In addition,
      camel WP succeeded to overcome the therapeutic drawback posed from rosuvastatin
      therapy alone with minimal side effects.

PMID- 29349447
TI  - Theoretical study on the charge transport in single crystals of TCNQ, F2-TCNQ and
      F4-TCNQ.
AB  - 2,5-Difluoro-7,7,8,8-tetracyanoquinodimethane (F2-TCNQ) was recently reported to
      display excellent electron transport properties in single crystal field-effect
      transistors (FETs). Its carrier mobility can reach 25 cm2 V-1 s-1 in devices.
      However, its counterparts TCNQ and F4-TCNQ (tetrafluoro-7,7,8,8
      tetracyanoquinodimethane) do not exhibit the same highly efficient behavior. To
      better understand this significant difference in charge carrier mobility, a
      multiscale approach combining semiclassical Marcus hopping theory, a quantum
      nuclear enabled hopping model and molecular dynamics simulations was performed to
      assess the electron mobilities of the Fn-TCNQ (n = 0, 2, 4) systems in this work.
      The results indicated that the outstanding electron transport behavior of F2-TCNQ
      arises from its effective 3D charge carrier percolation network due to its
      special packing motif and the nuclear tunneling effect. Moreover, the poor
      transport properties of TCNQ and F4-TCNQ stem from their invalid packing and
      strong thermal disorder. It was found that Marcus theory underestimated the
      mobilities for all the systems, while the quantum model with the nuclear
      tunneling effect provided reasonable results compared to experiments. Moreover,
      the band-like transport behavior of F2-TCNQ was well described by the quantum
      nuclear enabled hopping model. In addition, quantum theory of atoms in molecules
      (QTAIM) analysis and symmetry-adapted perturbation theory (SAPT) were used to
      characterize the intermolecular interactions in TCNQ, F2-TCNQ and F4-TCNQ
      crystals. A primary understanding of various noncovalent interaction responses
      for crystal formation is crucial to understand the structure-property
      relationships in organic molecular materials.

PMID- 29349448
TI  - A study on platinum(iv) species containing an estrogen receptor modulator to
      reverse tamoxifen resistance of breast cancer.
AB  - Several dual-action Tam-Pt(iv) complexes derived from tamoxifen (Tam) and
      platinum(ii) drugs were designed and synthesized for targeting estrogen receptors
      (ERs) and DNA. These novel compounds not only exhibited potent cytotoxicity
      against breast cancer cells, but also reversed the tamoxifen resistance of TamR
      MCF-7 cancer cells. Computational docking assays together with cellular uptake
      data demonstrated that the ER ligand portion of these conjugates plays a
      targeting role in ER-positive tumor cells and promotes the uptake of platinum via
      an estrogen receptor-mediated pathway. A study on the preliminary mechanism of
      the typical conjugate, complex 1, revealed that the Tam-Pt(iv) complex induced
      apoptosis via the mitochondrial-dependent apoptosis pathway mediated through the
      activation of caspase 3 and PARP proteins. These results suggested that the
      conjugation of estrogen receptor modulators with the platinum moiety could
      facilitate a selective enrichment of platinum in estrogen-positive tumors and
      possibly broaden the scope of ER ligand clinical use to resistant breast tumors.

PMID- 29349449
TI  - Local and global aromaticity in a molecular carbon nanobelt: insights from
      magnetic response properties in neutral and charged species.
AB  - The formation of carbon nanobelt made exclusively from fused benzene rings has
      recently been achieved. Our results reveal an interesting shift from a local
      aromatic character constrained in each of the six aromatic Clar sextets (6pi
      electron circuit) to a global aromatic character in charged species (+2 and -2)
      involving the overall pi-circuit from the molecular nanobelt. This demonstrates
      the suppression of the local aromatic character in favor of a global aromaticity
      by selecting the oxidation state of the carbon nanobelt, giving rise to a
      shielding cone extended within the structure.

PMID- 29349450
TI  - Complex patchy colloids shaped from deformable seed particles through capillary
      interactions.
AB  - We investigate the mechanisms underlying the reconfiguration of random aggregates
      of spheres through capillary interactions, the so-called "colloidal recycling"
      method, to fabricate a wide variety of patchy particles. We explore the influence
      of capillary forces on clusters of deformable seed particles by systematically
      varying the crosslink density of the spherical seeds. Spheres with a poorly
      crosslinked polymer network strongly deform due to capillary forces and merge
      into large spheres. With increasing crosslink density and therefore rigidity, the
      shape of the spheres is increasingly preserved during reconfiguration, yielding
      patchy particles of well-defined shape for up to five spheres. In particular, we
      find that the aspect ratio between the length and width of dumbbells, L/W,
      increases with the crosslink density (cd) as L/W = B - A.exp(-cd/C). For clusters
      consisting of more than five spheres, the particle deformability furthermore
      determines the patch arrangement of the resulting particles. The reconfiguration
      pathway of clusters of six densely or poorly crosslinked seeds leads to
      octahedral and polytetrahedral shaped patchy particles, respectively. For seven
      particles several geometries were obtained with a preference for pentagonal
      dipyramids by the rigid spheres, while the soft spheres do rarely arrive in these
      structures. Even larger clusters of over 15 particles form non-uniform often
      aspherical shapes. We discuss that the reconfiguration pathway is largely
      influenced by confinement and geometric constraints. The key factor which
      dominates during reconfiguration depends on the deformability of the spherical
      seed particles.

PMID- 29349451
TI  - On the turn-inducing properties of asparagine: the structuring role of the amide
      side chain, from isolated model peptides to crystallized proteins.
AB  - Asparagine (Asn) is a powerful turn-inducer residue, with a large propensity to
      occupy the second position in the central region of beta-turns of proteins. The
      present work aims at investigating the role of a local anchoring between the Asn
      side chain and the main chain in this remarkable property. For this purpose, the
      H-bonding patterns of an asparagine residue in an isolated protein chain fragment
      forming a gamma- or a beta-turn have been determined using IR/UV double resonance
      gas phase spectroscopy on laser-desorbed, jet-cooled short models in conjunction
      with relevant quantum chemistry calculations. These gas phase data provide
      evidence for an original double anchoring linking the Asn primary amide side
      chain (SC), which adopts a gauche+ rotameric form, to its main chain (MC) local
      environment. From both IR spectroscopic evidence (H-bond induced red shifts) and
      quantum chemistry, Asn SC is found to behave as a stronger H-bond acceptor than
      donor, resulting in stronger MC->SC H-bonds than SC->MC ones. These gas phase
      structural data, relevant to a hydrophobic environment, have been used as a
      reference to assess the anchoring taking place in high resolution crystallized
      proteins of the Protein Data Bank. This approach reveals that, when the SC adopts
      a gauche+ orientation, the stronger MC->SC bonds are preserved in many cases
      whereas the SC->MC bonds are always disrupted, in qualitative agreement with the
      gas phase ranking of these interactions. Most interestingly, when Asn occupies
      the second position of central part of a beta-turn (i.e., the very turn-inducer
      position), the MC->SC H-bonds are also disrupted and replaced by a water-mediated
      SC to MC anchoring. Owing to the specific features of the hydrated Asn side
      chain, we propose that it could be a turn precursor structure, able to facilitate
      turn formation in the early events of the folding process.

PMID- 29349452
TI  - Barriometry - an enhanced database of accurate barrier heights for gas-phase
      reactions.
AB  - The kinetics of many reactions are critically dependent upon the barrier heights
      for which accurate determination can be difficult. From the perspective of
      attaining such quantities using computational quantum chemistry, it is important
      to appropriately validate routine and efficient methodologies such as density
      functional theory (DFT) procedures. In the present study, we embark on the
      journey of establishing diverse databases using a consistent high-level quantum
      chemistry procedure, against which new and existing methodologies can be
      assessed. Thus, we have used the composite protocol W3X-L to provide more than
      100 refined reference values for existing databases [e.g., Y. Zhao and D. G.
      Truhlar, J. Phys. Chem. A, 2005, 109, 5656] and additionally establish benchmark
      data that are of interest to atmospheric and combustion chemists. While our
      endeavor has just begun, assessment of various DFT methods with our existing
      results lends support to the use of MN15 as an adequate method for general
      kinetics applications. We also recommend the use of less-costly W2X and WG
      composite protocols for obtaining adequately accurate reference thermochemical
      values for larger molecular systems.

PMID- 29349453
TI  - A QM/MM and QM/QM/MM study of Kerr, Cotton-Mouton and Jones linear birefringences
      in liquid acetonitrile.
AB  - QM/MM and QM/QM/MM protocols are applied to the ab initio study of the three
      linear birefringences Kerr, Cotton-Mouton, and Jones, as shown by acetonitrile in
      the gas and pure liquid phases. The relevant first-order properties as well as
      linear, quadratic, and cubic frequency-dependent response functions were computed
      using time-dependent Kohn-Sham density-functional theory with use of the standard
      CAM-B3LYP functional. In the liquid phase, a series of room temperature (293.15
      K) molecular dynamics snapshots were selected, for which averaged values of the
      observables were obtained at an optical wavelength of 632.8 nm. The
      birefringences were computed for electric and magnetic induction fields
      corresponding to the laboratory setup previously employed by T. Roth and G. L. J.
      A. Rikken in Phys. Rev. Lett., 2000, 85, 4478. Under these conditions,
      acetonitrile is shown to exhibit a weak Jones response-in fact roughly 6.5 times
      smaller than the limit of detection of the apparatus employed in the measurements
      mentioned above. A comparison is made with the corresponding gas-phase results
      and an assessment is made of the index of measurability, estimating the degree of
      overlap of the three birefringences in actual measurements. For acetonitrile, it
      is shown that this index is a factor of 3.6 and 6.7 larger than that of
      methylcyclopentadienyl-Mn-tricarbonyl and cyclohexadienyl-Fe-tricarbonyl,
      respectively-two compounds reported in Phys. Rev. Lett., 2000, 85, 4478 to
      exhibit a strong Jones signal.

PMID- 29349454
TI  - Adsorption and binding dynamics of graphene-supported phospholipid membranes
      using the QCM-D technique.
AB  - We report on the adsorption dynamics of phospholipid membranes on graphene-coated
      substrates using the quartz crystal microbalance with dissipation monitoring (QCM
      D) technique. We compare the lipid vesicle interaction and membrane formation on
      gold and silicon dioxide QCM crystal surfaces with their graphene oxide (GO) and
      reduced (r)GO coated counterparts, and report on the different lipid structures
      obtained. We establish graphene derivative coatings as support surfaces with
      tuneable hydrophobicity for the formation of controllable lipid structures. One
      structure of interest formed is lipid monolayer membranes which were formed on
      rGO, which are otherwise challenging to produce. We also demonstrate and monitor
      biotin-avidin binding on such a membrane, which will then serve as a platform for
      a wide range of biosensing applications. The QCM-D technique could be extended to
      both fundamental studies and applications of other covalent and non-covalent
      interactions in 2-dimensional materials.

PMID- 29349455
TI  - On the H2 interactions with transition metal adatoms supported on graphene: a
      systematic density functional study.
AB  - The attachment of H2 to the full set of transition metal (TM) adatoms supported
      on graphene is studied by using density functional theory. Methodology validation
      calculations on the interactions of H2 with benzene and graphene show that any of
      the vdW corrections under study, the Grimme D2, D3, D3 with Becke-Jonson damping
      (D3BJ), and Tkatchenko-Scheffler methods, applied on the PBE functional, are
      similarly accurate in describing such subtle interactions, with an accuracy of
      almost 2 kJ mol-1 compared to experiments. The PBE-D3 results show that H2
      physisorbs on especially stable d5 or d10 TMs. In other 5d metals, and the
      rightmost 3d and 4d ones, H2 dissociates, and only for Y, Mn, Fe, and Zr the H2
      binds strongly enough for its storage in the so-called Kubas mode, where the H2
      bond is sensibly elongated. Other metals (Co, Ni, Ru, Rh and Pd) feature also an
      elongated Kubas mode, interesting as well for H2 storage. Sc and Ti display a
      Kubas modes especially suited, given their lightness, for meeting the gravimetric
      requirements. The H2 interactions with TM adatoms imply a TM -> H2 charge
      transfer, although the magnetic moment of the system tends to remain intact,
      except for the early 5d TMs, where the unpaired electron transfer seems to be
      associated with the H2 bond breakage.

PMID- 29349456
TI  - Effects of carotenoids on lipid bilayers.
AB  - Carotenoids have been found to be important in improving the integrity of
      biomembranes in eukaryotes. However, the molecular details of how carotenoids
      modulate the physical properties of biomembranes are unknown. To this end, we
      have conducted a series of molecular dynamics simulations of different
      biologically-relevant membranes in the presence of carotenoids. The carotenoid
      effect on the membrane was found to be specific to the identity of the carotenoid
      and the composition of the membrane itself. Therefore, different classes of
      carotenoids produce a different effect on the membrane, and different membrane
      phases are affected differently by carotenoids. It is apparent from our data that
      carotenoids do trigger the bilayer to become thinner. The mechanism by which this
      occurs depends on two competing factors, the ability of the lipid tails of
      opposing monolayers to either (1) compress or (2) interdigitate as the bilayer
      condenses. Indeed, carotenoids directly influence the physical properties via
      these two mechanisms, thus compacting the bilayer. However, the degree to which
      these competing mechanisms are utilized depends on the bilayer phase and the
      carotenoid identity.

PMID- 29349457
TI  - Effects of tetrahedral DNA nanostructures on autophagy in chondrocytes.
AB  - Tetrahedral DNA nanostructures (TDNs) have gathered great attention and are being
      widely used in biomedicine. We demonstrated that autophagy increased after
      exposure to TDNs (250 nM) along with the up-regulation of several autophagy
      related genes and proteins. TDNs enhanced cell autophagy through the
      PI3K/AKT/mTOR signaling pathway.

PMID- 29349458
TI  - Trends in adsorption of electrocatalytic water splitting intermediates on cubic
      ABO3 oxides.
AB  - The reactivity of solid oxide surfaces towards adsorption of oxygen and hydrogen
      is a key metric for the design of new catalysts for electrochemical water
      splitting. In this paper, we report on trends in the adsorption energy of
      different adsorbed intermediates derived from the oxidation and reduction of
      water for ternary ABO3 oxides in the cubic perovskite structure. Our findings
      support a previously reported trend that rationalizes the observed lower bound in
      oxygen evolution (OER) overpotentials from correlations in OH* and OOH*
      adsorption energies. In addition, we report hydrogen adsorption energies that may
      be used to estimate hydrogen evolution (HER) overpotentials along with potential
      metrics for electrochemical metastability in reducing environments. We also
      report and discuss trends between atom-projected density of states and adsorption
      energies, which may enable a design criteria from the local electronic structure
      of the active site.

PMID- 29349459
TI  - A versatile single molecular precursor for the synthesis of layered oxide cathode
      materials for Li-ion batteries.
AB  - A carbonyl-bridged single molecular precursor LiTM(acac)3 [transition metal (TM)
      = cobalt/manganese/nickel (Co/Mn/Ni), acac = acetylacetone], featuring a one
      dimensional chain structure, was designed and applied to achieve the layered
      oxide cathode materials: LiTMO2 (TM = Ni/Mn/Co, NMC). As examples, layered
      oxides, primary LiCoO2, binary LiNi0.8Co0.2O2 and ternary LiNi0.5Mn0.3Co0.2O2
      were successfully prepared to be used as cathode materials. When they are applied
      to lithium-ion batteries (LIBs), all exhibit good electrochemical performance
      because of their unique morphology and great uniformity of element distribution.
      This versatile precursor is predicted to accommodate many other metal cations,
      such as aluminum (Al3+), iron (Fe2+), and sodium (Na+), because of the
      flexibility of organic ligand, which not only facilitates the doping-modification
      of the NMC system, but also enables synthesis of Na-ion layered oxides. This
      opens a new direction of research for the synthesis of high-performance layered
      oxide cathode materials for LIBs.

PMID- 29349460
TI  - A combined theoretical and experimental investigation on the influence of the
      bromine substitution pattern on the photophysics of conjugated organic
      chromophores.
AB  - A large series of structurally related two-photon photosensitizers with heavy
      atom substitution were synthesized and evaluated through a combined spectroscopic
      (steady-state and time resolved), photophysical and computational study. Our aim
      was to identify some relevant parameters related to their excited state dynamics
      including photo-induced singlet oxygen generation. Although these dynamics result
      from the interplay of many factors, we show that the triplet excited state
      generation kinetics can generally be correlated with the calculated values of
      both the spin-orbit coupling and the energy gap between S1 and T1 states, which
      themselves mostly depend on the positioning of the heavy atoms along the pi
      conjugated structure rather than their number.

PMID- 29349461
TI  - Oxygen vacancy rich Cu2O based composite material with nitrogen doped carbon as
      matrix for photocatalytic H2 production and organic pollutant removal.
AB  - A nitrogen doped carbon matrix supported Cu2O composite material (Cu/Cu2O@NC) was
      fabricated successfully with a coordination polymer as precursor through
      calcination. In this composite material, Cu2O particles with a size of about 6-10
      nm were dispersed evenly in the nitrogen doped carbon matrix. After calcination,
      some coordinated nitrogen atoms were doped in the lattice of Cu2O and replace
      oxygen atoms, thus generating a large number of oxygen vacancies. In Cu/Cu2O@NC,
      the existence of oxygen vacancies has been confirmed by electron spin resonance
      (ESR) and X-ray photoelectron spectroscopy (XPS). Under visible light
      irradiation, Cu/Cu2O@NC exhibits excellent H2 production with the rate of 379.6
      MUmol h-1 g-1. Its photocatalytic activity affects organic dyes, such as
      Rhodamine B (RhB) and methyl orange (MO). In addition to photocatalysis,
      Cu/Cu2O@NC also exhibits striking catalytic activity in reductive conversion of 4
      nitrophenol to 4-aminophenol with in presence of sodium borohydride (NaBH4). The
      conversion efficiency reaches almost 100% in 250 s with the quantity of
      Cu/Cu2O@NC as low as 5 mg. The outstanding H2 production and organic pollutants
      removal are attributed to the oxygen vacancy. We expect that Cu/Cu2O@NC will find
      its way as a new resource for hydrogen energy as well as a promising material in
      water purification.

PMID- 29349462
TI  - Self-assembly of bis-salphen compounds: from semiflexible chains to webs of
      nanorings.
AB  - The recently-observed self-assembly of certain salphen-based compounds into
      neuron-like networks of microrings interconnected with nano-thin strings may
      suggest a new highly-potent tool for nanoscale patterning. However, the mechanism
      behind such phenomena needs to be clarified before they can be applied in
      materials design. Here we show that, in contrast with what was initially
      presumed, the emergence of a "rings-and-rods" pattern is unlikely to be explained
      by merging, collapse and piercing of vesicles as in previously reported cases of
      nanorings self-assembly via non-bonding interactions. We propose an alternative
      explanation: the compounds under study form a 1D coordination polymer, the fibres
      of which are elastic enough to fold into toroidal globules upon solvent
      evaporation, while being able to link separate chains into extended networks.
      This becomes possible because the structure of the compound's scaffold is found
      to adopt a very different conformation from that inferred in the original work.
      Based on ab initio and molecular dynamics calculations we propose a step-by-step
      description of self-assembly process of a supramolecular structure which explains
      all the observed phenomena in a simple and clear way. The individual roles of the
      compound' s scaffold structure, coordination centres, functional groups and
      solvent effects are also explained, opening a route to control the morphology of
      self-assembled networks and to synthesize new compounds exhibiting similar
      behaviour.

PMID- 29349463
TI  - Stability and digestibility of one- or bi-layered medium-chain triglyceride
      emulsions with gum Arabic and whey protein isolates by pancreatic lipase in
      vitro.
AB  - Interfacial engineering approaches have been used to design functional foods so
      as to control lipase-induced digestion of emulsified lipids and release of
      bioactive lipophilic components in the gastrointestinal tract. In this study,
      emulsion droplets with the interface stabilized with gum Arabic (GA) and whey
      protein isolate (WPI) were prepared by mixing or sequential adsorption. WPI/GA
      intramolecular soluble complexes (ISCs) have superior emulsifying properties in
      stabilizing oil-in-water emulsions. The impact of the interfaces for WPI/GA ISC
      layered (one-layered) and double-layered emulsions formed by sequential
      deposition of WPI or GA on the lipolysis of emulsions was investigated using an
      in vitro simulated gastrointestinal model. Transglutaminase and dithiothreitol
      were introduced to crosslink the interfacial proteins and improve the interfacial
      stability. The ISC-layered emulsion was less stable to aggregation than the
      double-layered ones in simulated gastric fluid due to dissociation of ISCs caused
      by the electrostatic screening of ions and proteolysis of interfacial proteins
      driven by pepsin. The ISC-layered emulsion conferred a significant slower rate
      and extent of lipid digestion compared to the double-layered emulsions post
      gastric proteolysis (P < 0.05). It is presumed for the ISC-layered emulsion that
      the destabilization to aggregation and coalescence within the simulated
      gastrointestinal fluids and the steric hindrance of the robust and thick
      interfacial layer might contribute to delaying free fatty acids release. It
      suggests that both the initial interfacial properties and the stability of the
      emulsified lipid droplets within the simulated gastrointestinal fluids play an
      important role in determining the rate and extent of lipid digestion. It is
      predicted that direct destabilization of emulsified lipids using interfacial
      engineering approaches has the potential of modifying lipid digestibility or
      bioactive release at specific sites within the gastrointestinal tract.

PMID- 29349464
TI  - Boundary-induced nucleation control: a theoretical perspective.
AB  - The pre-patterning of a substrate to create energetically more attractive or
      repulsive regions allows one to generate a variety of structures in physical
      vapor deposition experiments. A particularly interesting structure is generated
      if the energetically attractive region forms a rectangular grid. For specific
      combinations of the particle flux, the substrate temperature and the lattice size
      it is possible to generate exactly one cluster per cell, giving rise to
      nucleation control. Here, we show that the experimental observations of
      nucleation control can be very well understood from a theoretical perspective.
      For this purpose we perform, on the one hand, kinetic Monte Carlo simulations
      and, on the other hand, use analytical scaling arguments to rationalize the
      observed behavior. For several observables, characterizing nucleation control,
      very good agreement is found between experiment and theory. This underlines the
      generality of the presented mechanism to control the deposition of materials by
      manipulation of the direct environment.

PMID- 29349465
TI  - Exploring candidate biomarkers for lung and prostate cancers using gene
      expression and flux variability analysis.
AB  - Genome-scale metabolic models have provided valuable resources for exploring
      changes in metabolism under normal and cancer conditions. However, metabolism
      itself is strongly linked to gene expression, so integration of gene expression
      data into metabolic models might improve the detection of genes involved in the
      control of tumor progression. Herein, we considered gene expression data as extra
      constraints to enhance the predictive powers of metabolic models. We
      reconstructed genome-scale metabolic models for lung and prostate, under normal
      and cancer conditions to detect the major genes associated with critical
      subsystems during tumor development. Furthermore, we utilized gene expression
      data in combination with an information theory-based approach to reconstruct co
      expression networks of the human lung and prostate in both cohorts. Our results
      revealed 19 genes as candidate biomarkers for lung and prostate cancer cells.
      This study also revealed that the development of a complementary approach
      (integration of gene expression and metabolic profiles) could lead to proposing
      novel biomarkers and suggesting renovated cancer treatment strategies which have
      not been possible to detect using either of the methods alone.

PMID- 29349466
TI  - Dynamics of networks in a viscoelastic and active environment.
AB  - We investigate the dynamics of fractals and other networks in a viscoelastic and
      active environment. The viscoelastic dynamics is modeled based on the generalized
      Langevin equation, where the activity is introduced to it by means of the
      exponentially correlated noise. The intramolecular interactions are taken into
      account by the bead-spring picture. The microscopic connectivity (studied in the
      form of Vicsek fractals, of dual Sierpinski gaskets, of NTD trees, and of a
      family of deterministic small-world networks) reveals itself in the multiscale
      monomeric dynamics, which shows vastly different behaviors in the active and
      passive baths. In particular, the dynamics under active forces leads to a
      swelling that is characterized through power laws which are not present in the
      passive case. In all cases, the dynamics reflects the broad scaling behavior of
      the density of states and not necessarily the maximal relaxation time of the
      structures in a passive bath, as it is exemplified on the NTD trees.

PMID- 29349467
TI  - Lysine-derived, pH-sensitive and biodegradable poly(beta-aminoester urethane)
      networks and their local drug delivery behaviour.
AB  - In this study, a series of covalently crosslinked, l-lysine based poly(beta
      aminoester urethane) (LPBAEU) networks with good biodegradability and pH
      sensitivity was reported. The effect of hydrophilic/hydrophobic characteristics
      and diacrylate/amine molar ratio on the structure, swelling and degradation
      behaviour of the networks was investigated. The water transport mechanism and
      dynamic swelling behavior of the LPBAEU networks were strongly affected by medium
      pH, and swelling amounts up to 252.2% and 148.7% were observed at pH 5.6 and pH
      7.4, respectively. It was found that water diffusion within the networks followed
      a non-Fickian mechanism. The LPBAEU network with the highest diacrylate/amine
      molar ratio exhibited the highest tensile strength and Young's modulus. In vitro
      mass losses of networks showed that the degradation rate of LPBAEU networks can
      be adjusted from 4 to 14 days. LPBAEU networks also supported loading of
      doxycycline hyclate (DH) and in vitro release studies demonstrated that release
      of DH from the networks was substantially hindered in the neutral pH environment,
      with 20.9-56.2% DH release, whereas DH release was accelerated under mild acidic
      conditions, with a release percentage of 36.6-99.6%. The release data were fitted
      to different mathematical models and the obtained results confirmed that these
      networks released DH in a non-Fickian mechanism. The results of this research
      support the idea that pH-responsive LPBAEU networks may find potential
      applications in local drug delivery.

PMID- 29349468
TI  - Absolute and relative-rate measurement of the rate coefficient for reaction of
      perfluoro ethyl vinyl ether (C2F5OCF[double bond, length as m-dash]CF2) with OH.
AB  - The rate coefficient (k1) for the reaction of OH radicals with perfluoro ethyl
      vinyl ether (PEVE, C2F5OCF[double bond, length as m-dash]CF2) has been measured
      as a function of temperature (T = 207-300 K) using the technique of pulsed laser
      photolysis with detection of OH by laser-induced fluorescence (PLP-LIF) at
      pressures of 50 or 100 Torr N2 bath gas. In addition, the rate coefficient was
      measured at 298 K and in one atmosphere of air by the relative-rate technique
      with loss of PEVE and reference reactant monitored in situ by IR absorption
      spectroscopy. The rate coefficient has a negative temperature dependence which
      can be parameterized as: k1(T) = 6.0 * 10-13 exp[(480 +/- 38/T)] cm3 molecule-1 s
      1 and a room temperature value of k1 (298 K) = (3.0 +/- 0.3) * 10-12 cm3 molecule
      1 s-1. Highly accurate rate coefficients from the PLP-LIF experiments were
      achieved by optical on-line measurements of PEVE and by performing the
      measurements at two different apparatuses. The large rate coefficient and the
      temperature dependence indicate that the reaction proceeds via OH addition to the
      C[double bond, length as m-dash]C double bond, the high pressure limit already
      being reached at 50 Torr N2. Based on the rate coefficient and average OH levels,
      the atmospheric lifetime of PEVE was estimated to be a few days.

PMID- 29349469
TI  - Dopant-dependent crystallization and photothermal effect of Sb-doped SnO2
      nanoparticles as stable theranostic nanoagents for tumor ablation.
AB  - Ideal theranostic nanoagents should be "all-in-one" type nanocrystals that have a
      single-semiconductor component and all-required properties (such as imaging and
      photothermal effects), but most semiconductor nanocrystals do not have these
      required properties. With SnO2 as a model of a typical wide-band semiconductor,
      we report the tuning from UV-responsive SnO2 to blue SnO2 nanocrystals with
      imaging ability and a Sb-doping-dependent photothermal effect. Sb-Doped SnO2
      nanocrystals were prepared by heating SbCl3 and SnCl4 in benzyl alcohol solution
      through a facile solvothermal route. When the SbCl3/SnCl4 molar ratio increases
      from 0 to 0.2/1, the obtained samples exhibit an increased photothermal effect
      under the irradiation of a 1064 nm laser, accompanied by gradually decreased size
      and crystallinity. With a further increase of the molar ratio from 0.3/1.0 to
      1.0/1.0, the resulting samples demonstrate the tetragonal SnO2 phase with
      amorphous-like compounds and they show no obvious enhancement of a photothermal
      effect. After a surface modification with biological molecules, the optimized
      Sb0.2-SnO2 nanocrystals demonstrated good stability and a high photothermal
      conversion efficiency of 48.3% as well as low cytotoxicity. When Sb0.2-SnO2 was
      injected into a tumor of mice, the tumor could be simultaneously detected by X
      ray computed tomography (CT) and photoacoustic (PA) imaging, and then thermally
      ablated when exposed to a 1064 nm laser. Therefore, these nanocrystals can be
      used as "all-in-one" type nanoagents for imaging guided photothermal ablation of
      tumors under the irradiation of a laser in the second bio-transparent window.

PMID- 29349475
TI  - Continuous splitting of aqueous droplets at the interface of co-flowing
      immiscible oil streams in a microchannel.
AB  - We report the continuous splitting of aqueous droplets at the interface between
      two co-flowing immiscible oil streams in a microchannel. The aqueous droplets
      initially present in a primary continuous stream (CP1) migrate into a secondary
      continuous stream (CP2) when the ratio of the non-inertial lift force to the
      interfacial tension force exceeds a critical value (K. S. Jayaprakash, U.
      Banerjee and A. K. Sen, Langmuir, 2016, 32, 2136-2143). Here, experiments were
      performed to understand the droplet splitting phenomenon and demonstrate the
      splitting of droplets encapsulating microbeads and cells. The results showed that
      the droplet splitting phenomenon is governed by the capillary number Ca, which is
      a function of the average shear stress across the channel, interfacial tension
      sigma between the CP1 and the droplet phase and the droplet length-scale L.
      Irrespective of the individual values of these parameters, droplet splitting was
      observed when the capillary number Ca exceeds a critical value Cacr, which was
      found to be a function of droplet to CP2 viscosity ratio lambda. The Cacr was
      found to be minimum for lambda ~ 1 but higher for droplets of lambda ? 1 and
      lambda ? 1. The sizes of the primary and secondary daughter and migrated droplets
      (i.e. Lp|sD and Lp|sM) were found to increase linearly with the increase in the
      size of the primary or secondary parent droplets (Lp|sP). Splitting of parent
      droplets encapsulating a single microbead or PBMC showed that after splitting,
      the presence of the microbead or PBMC in the daughter or migrated droplets
      depends on the ratio of the size of the migrated droplets to that of the parent
      droplet (i.e. VM/VP). Finally, splitting of parent droplets containing two or
      more microbeads or cells into droplets containing a single particle or cell was
      demonstrated. A new paradigm of droplet splitting is reported that could find
      applications in soft matter and single-cell studies.

PMID- 29349476
TI  - Monitoring the formation of PtNi nanoalloys supported on hollow graphitic spheres
      using in situ pair distribution function analysis.
AB  - This article aims to address the formation and the structural
      disordering/ordering phenomena of PtNi nanoalloys supported on hollow graphitic
      spheres (HGSs) using pair distribution function (PDF) analysis under ex situ/in
      situ data collection conditions. Starting from small nanoparticles (10-15 A in
      diameter) embedded in HGSs, structural changes were monitored during stepwise
      heating and cooling of the sample using in situ PDF analysis. In order to
      evaluate the conventional synthesis route for the production of PtNi nanoalloys
      supported on HGSs, ex situ PDF experiments were performed before and after heat
      treatment in a furnace. The studies demonstrate that the local structure of the
      in situ synthesised PtNi nanoalloy differs from its ex situ synthesised
      counterpart. A partially ordered PtNi nanoalloy was obtained during the stepwise
      in situ cooling of the precursor, whereas the conventional ex situ synthesis
      route did not lead to the formation of an ordered crystal structure. In this
      study we could show that rapid heating and cooling results in a disordered PtNi
      alloy whereas slow heating and cooling leads to disorder-order transitions in
      PtNi.

PMID- 29349477
TI  - Isomerism and reactivity of nickel(ii) acetylacetonate bis(thiosemicarbazone)
      complexes.
AB  - The complexation of nickel(ii) with acetylacetonate bis(thiosemicarbazone) N2S2
      ligands with varying substituents has revealed that two isomers can exist
      independently in solution. These isomers differ according to the formation of
      either a 5,6,5-membered (symmetric) or a 4,7,5-membered (asymmetric) chelate ring
      arrangement. These two isomers have distinctly different properties. The
      symmetric complex (sym-[Ni(acacR)]) is unstable in the presence of air and slowly
      converts to the oxidised analogue sym-[Ni(acacRO)] with a carbonyl group
      installed at the apical C-atom. The mechanism of this O-atom transfer reaction is
      still unclear but kinetic and spectroelectrochemical experiments in addition to
      Density Functional Theory calculations have identified a single electron oxidised
      NiII-ligand radical complex as a key intermediate. By contrast the asymmetric
      complex, asym-[Ni(acacR)] is inert to ligand oxidation.

PMID- 29349478
TI  - Affinity to host population stimulates physical growth in adult offspring of
      Turkish migrants in Germany.
AB  - ABSTRACT: Because of political conflicts and climate change, migration will be
      increased worldwide and integration in host societies is a challenge also for
      migrants. We hypothesize that migrants, who take up the challenge in a new social
      environment are taller than migrants who do not pose this challenge. We analyze
      by a questionnaire possible social, nutritional and ethnic influencing factors to
      body height (BH) of adult offspring of Turkish migrants (n = 82, 39 males) aged
      from 18 to 34 years (mean age 24.6 years). The results of multiple regression
      (downward selection) show that the more a male adult offspring of Turkish
      migrants feels like belonging to the Turkish culture, the smaller he is (95% CI, 
      3.79, -0.323). Further, the more a male adult offspring of Turkish migrants feels
      like belonging to the German culture, the taller he is (95% CI, -0.152, 1.738).
      We discussed it comparable to primates taking up their challenge in dominance,
      where as a result their body size increase is associated with higher IGF-1 level.
      IGF-1 is associated with emotional belonging and has a fundamental role in the
      regulation of metabolism and growth of the human body. With all pilot
      characteristics of our study results show that the successful challenge of
      integration in a new society is strongly associated with the emotional
      integration and identification in the sense of a personal sense of belonging to
      society. We discuss taller BH as a signal of social growth adjustment. In this
      sense, a secular trend of BH adaptation of migrants to hosts is a sign of
      integration.

PMID- 29349479
TI  - Resilience and protective factors among people with a history of child
      maltreatment: a systematic review.
AB  - PURPOSE: To provide an overview of resilience and protective factors associated
      with a better life following child maltreatment exposure, to compare protective
      factors across specific subtypes of maltreatment, and to explore existing issues
      in the current state of the literature. METHODS: Electronic databases and grey
      literature up to October 2017 were systematically searched for English language
      with observational study designs for the research on resilience and childhood
      maltreatment. Systematic review and qualitative approaches were used to
      synthesize the results. Study quality and heterogeneity were also examined.
      RESULTS: Initial screening of titles and abstracts resulted in 247 papers being
      reviewed. A total of 85 articles met eligibility criteria of this review. Most of
      these studies had low or middle study quality. There were two subgroups of
      studies reviewed: (1) 11 studies examined whether resilience protected against
      the negative consequence of childhood maltreatment, and, (2) 75 studies explored
      what protective factor was associated with a kind of adaptive functioning.
      Although the conceptualization of resilience significantly varied from study to
      study, protective factors associated with resilience at individual, familial, and
      societal levels reduced the likelihood of negative consequences of childhood
      maltreatment. Negative consequences following childhood maltreatment can be
      prevented or moderated if protective factors are provided in time. Future
      research needs to address the conceptualization issue of resilience. CONCLUSIONS:
      Public and population mental health preventions should focus on early childhood
      and apply preventive strategies as early as possible. Cost-effective studies
      should be considered in the evaluation of resilience prevention program.

PMID- 29349480
TI  - Posture modulates the sensitivity of the H-reflex.
AB  - The effect of body posture on the human soleus H-reflex via electrical
      stimulation of the tibial nerve at the popliteal fossa was studied. All
      parameters that may influence the reflex were controlled stringently. H-reflexes
      were elicited in three different body postures while keeping the level of
      background muscle activation to a minimum. The H-reflex curve relative to the M
      wave curve did not change significantly in any of the body postures. However, the
      maximal H-reflex amplitude significantly increased in the prone position compared
      with the sitting (p = 0.02) and standing positions (p = 0.01). The background
      level of electrical activity of the soleus muscle did not significantly change
      during varying body postures. Together, these findings indicate that the
      effectiveness of the spindle primary afferent synapse on the soleus motor neuron
      pool changes significantly in prone position as compared to sitting and standing
      positions. Given that we have controlled the confounding factors excluding the
      head position relative to the gravity and the receptors that may be
      differentially activated at varying body postures such as the proprioceptors, it
      is concluded that the tonic activity from these receptors may presynaptically
      interfere with the effectiveness of the spindle primary afferent synapses on the
      soleus motor neurons.

PMID- 29349481
TI  - Systematic review and comparison of national and international guidelines on
      diverticular disease.
AB  - PURPOSE: Diverticular disease is common and of increasing medical and economical
      importance. Various practice guidelines on diagnostic and treatment on this
      disease exist. We compared current guidelines on the disease in order to identify
      concordant and discordant recommendations. METHOD: Eleven national and
      international guidelines on diverticular disease published over the last 10 years
      have been identified by a systematic literature review on PubMed and compared in
      detail for 20 main and 51 subtopics. RESULTS: The available evidence for the most
      aspects was rated as moderate or low. There was concordance for the following
      items: Diagnosis of diverticulitis should be confirmed by imaging methods (10 of
      10 guidelines). Mild forms may be treated out-patient (10/10). Abscesses are
      treated non-surgically (9/9). Elective surgery should be indicated by individual
      patient-related factors, only, and be performed laparoscopically (10/10, 9/9
      respectively). Main differences were found in the questions of appropriate
      classification, imaging diagnostic (computed-tomography versus ultra-sound), need
      for antibiotics in out-patient treatment and mode of surgery for diverticular
      perforation. Despite growing evidence that antibiotics are not needed for
      treating mild diverticulitis, only 3/10 guidelines have corresponding
      recommendations. Hartmann's procedure has been abandoned several years ago and is
      now recommended for feculent peritonitis by the three most recent guidelines. In
      contrast, laparoscopic lavage without resection is not recommended anymore.
      CONCLUSION: There are dissents in the recommendations for central aspects
      regarding the diagnostic and treatment of diverticular disease in recently
      published guidelines.

PMID- 29349482
TI  - [Esophageal diverticula (excluding cricopharyngeal diverticula)].
AB  - Diverticula of the middle and lower third of the esophagus are commonly
      associated with esophageal motility disorders. The increase of intraluminal
      pressure leads to an outpouching of the mucosal and submucosal layers through the
      esophageal muscle coat. These pouches are also called false diverticula, because
      they only consist of the mucosal and submucosal esophageal layers. In contrast,
      the more rarely encountered true diverticula that retain the complete esophageal
      wall are generally associated with periesophageal granulomatous lymph node
      disease. Treatment of both true and false diverticula is generally indicated in
      symptomatic patients; however, even state of the art minimally invasive surgery
      is accompanied by considerable perioperative morbidity and should only be
      performed in carefully selected patients. This aim of this article is to
      summarize the available scientific evidence and to provide the reader with an
      updated guide to best clinical practice in the treatment of esophageal
      diverticula.

PMID- 29349483
TI  - Surgical Outcomes of Primary Versus Post-Neoadjuvant Chemotherapy Breast
      Conservation Surgery: A Comparative Study from a Developing Country.
AB  - INTRODUCTION: In India and other developing countries, breast conservation
      surgery (BCS) rates in breast cancer patients are low due to advanced disease at
      presentation and misconceptions about BCS outcomes. Many patients presenting with
      large or locally advanced breast cancers (LABC) can be offered post-neoadjuvant
      chemotherapy (NACT) BCS, safety of which is not as well established as that of
      primary BCS. This retrospective study compared pathological and surgical outcome
      parameters in patients undergoing primary and post-NACT BCS. METHODS: All non
      metastatic breast cancer patients undergoing BCS during 2011-2015 with 1-year
      follow-up were included. Outcome parameters in form of margin infiltration,
      ipsilateral breast tumor recurrence (IBTR) rates and IBTR-free survival were
      compared between primary and post-NACT BCS patients groups. RESULTS: One hundred
      and twenty-nine patients underwent BCS; 95 underwent primary and 34 post-NACT
      BCS. Patients in both groups underwent similar multimodality treatment as per
      institutional protocols. Post-NACT patients more frequently required oncoplastic
      volume displacement or replacement surgery (p = 0.002). Re-excision of
      infiltrated margins was needed more frequently in primary BCS compared with post
      NACT BCS group (14.4 vs. 8.8%; p = 0.40). IBTR (Mean follow-up = 30.7 months) was
      seen in 8.8% post-NACT patients compared with 2.1% primary BCS (p = 0.114). IBTR
      free survival did not differ significantly between the groups in stage-wise
      comparison. CONCLUSION: Post-NACT BCS is safe even in large tumors and LABC,
      though many require oncoplastic procedures for satisfactory cosmesis. In a
      developing country where many patients present with large breast cancers or LABC,
      the benefits of BCS can be offered to a majority with the help of NACT, without
      compromising the chances of cure.

PMID- 29349484
TI  - Overall Survival of Papillary Thyroid Carcinoma Patients: A Single-Institution
      Long-Term Follow-Up of 5897 Patients.
AB  - INTRODUCTION: Papillary thyroid carcinoma (PTC) generally shows an excellent
      prognosis except in cases with aggressive backgrounds or clinicopathological
      features. Although the cause-specific survival (CSS) of PTC patients has been
      extensively investigated, the overall survival (OS) of these patients is unclear.
      We herein investigated both the OS and CSS of a large PTC patient series.
      MATERIALS AND METHODS: We enrolled 5897 PTC patients who underwent initial
      surgery between 1987 and 2005 (658 males and 5339 females; median age 51 years).
      Their median postoperative follow-up period was 177 months. Univariate and
      multivariate analyses for OS and CSS assessed the effects of gender, older age
      (>=55 years), distant metastasis at diagnosis (M1), significant extrathyroid
      extension, tumor size (cutoffs 2 and 4 cm), large node metastasis (N >= 3 cm),
      and extranodal tumor extension. RESULTS: To date, 387 patients (7%) in this
      series have died from various causes, including 117 (2%) due to PTC. The 10-, 15
      , and 20-year OS rates are 97, 95, and 90%, respectively. Older age and M1 were
      important prognostic factors for OS and CSS. Older age was a more significant
      factor than M1 for OS and vice versa for CSS. In the older patients, M1 was a
      prominent prognostic factor for both OS and CSS. In the young patients, M1 had
      less prognostic impact than in the older patients, and the prognostic values of
      M1 and N >= 3 cm for OS and CSS were identical and similar, respectively.
      CONCLUSIONS: The most important prognostic value for OS was patient age,
      indicating that PTC is generally indolent. However, the control of distant
      metastasis in older patients remains a future challenge in order to further
      improve their OS and CSS. PTC of >=3 cm in young patients should be carefully
      followed, even in the absence of metastases, and these patients should undergo
      aggressive therapies for recurrent lesions and metastases.

PMID- 29349485
TI  - Undiagnosed Primary Hyperparathyroidism and Recurrent Miscarriage: The First
      Prospective Pilot Study.
AB  - BACKGROUND: Primary hyperparathyroidism (pHPT) in pregnancy is reported to be
      associated with significant maternal and foetal complications and an up to
      threefold increase in the risk of miscarriage. However, the true incidence of
      pHPT in pregnancy, complete and miscarried, is unknown and there are no data on
      the prevalence of undiagnosed pHPT in recurrent miscarriage (RM) (>=3 consecutive
      miscarriages under 24-week gestation). This is the first prospective study aiming
      to establish the prevalence of undiagnosed pHPT in RM. METHODS: Following UK
      National ethics committee approval, women who had experienced 3 or more
      consecutive miscarriages were recruited from a nationwide RM clinic. Serum
      corrected calcium, phosphate, PTH and vitamin D were evaluated. Patients with
      raised serum calcium and/or PTH were recalled for confirmatory tests. Power
      calculations suggested that a minimum of 272 patients were required to
      demonstrate a clinically significant incidence of pHPT. RESULTS: Three hundred
      women were recruited, median age 35 years (range 19-42). Eleven patients had
      incomplete data, leaving 289 patients suitable for analysis; 50/289 patients
      (17%) with abnormal tests were recalled. The prevalence of vitamin D deficiency
      (<25 nmol/l) and insufficiency (25-75 nmol/l) was 8.7 and 67.8%, respectively.
      One patient was diagnosed with pHPT (0.34%) and underwent successful
      parathyroidectomy. CONCLUSIONS: The prevalence of undiagnosed pHPT (0.34%) in RM
      in this study appears to be many times greater than the 0.05% expected in this
      age group. The findings of this pilot study merit follow-up with a larger-scale
      study. Routine serum calcium estimation is not currently undertaken in RM and
      should be considered.

PMID- 29349486
TI  - Hydatid Cyst of the Liver: A Challenge that can be Amplified Shifting from Open
      to Laparoscopic Surgery.

PMID- 29349487
TI  - Lay First Responder Training in Eastern Uganda: Leveraging Transportation
      Infrastructure to Build an Effective Prehospital Emergency Care Training Program.
AB  - BACKGROUND: Though road traffic injuries (RTIs) are a major cause of mortality in
      East Africa, few countries have emergency medical services. The aim was to create
      a sustainable and efficient prehospital lay first responder program, creating a
      system with lay first responders spread through the 53 motorcycle taxi stages of
      Iganga Municipality. METHODS: One hundred and fifty-four motorcycle taxi riders
      were taught a first aid curriculum in partnership with a local Red Cross first
      aid trainer and provided with a first aid kit following WHO guidelines for basic
      first aid. Pre- and post-survey tests measured first aid knowledge improvement
      over the course. Post-implementation incident report forms were collected from
      lay first responders after each patient encounter over 6 months. Follow-up
      interviews were conducted with 110 of 154 trainees, 9 months post-training.
      RESULTS: Improvement was measured across all five major first aid categories:
      bleeding control (56.9 vs. 79.7%), scene management (37.6 vs. 59.5%), airway and
      breathing (43.4 vs. 51.6%), recovery position (13.1 vs. 43.4%), and victim
      transport (88.2 vs. 94.3%). From the incident report findings, first responders
      treated 250 victims (82.8% RTI related) and encountered 24 deaths (9.6% of
      victims). Of the first aid skills, bleeding control and bandaging was used most
      often (55.2% of encounters). Lay first responders provided transport in 48.3% of
      encounters. Of 110 lay first responders surveyed, 70 of 76 who had used at least
      one skill felt "confident" in the care they provided. CONCLUSION: A prehospital
      care system composed of lay first responders can be developed leveraging existing
      transport organizations, offering a scalable alternative for LMICs, demonstrating
      usefulness in practice and measurable educational improvements in trauma skills
      for non-clinical lay responders.

PMID- 29349488
TI  - One-step synthesis of an 18F-labeled boron-derived methionine analog: a
      substitute for 11C-methionine?
AB  - Amino acid-based tracers have been extensively investigated for positron emission
      tomography (PET) imaging of brain tumors, and 11C-methionine (11C-MET) is one of
      the most extensively investigated. However, widespread clinical use of 11C-MET is
      challenging due to the short half-life of 11C and low radiolabeling yield. In
      this issue of the European Journal of Nuclear Medicine and Molecular Imaging,
      Yang and colleagues report an 18F-labeled boron-derived methionine analog, 18F-B
      MET, as a potential substitute for 11C-MET in PET imaging of glioma. The push
      button synthesis, highly efficient radiolabeling, and good imaging performance in
      glioma models make this tracer a promising candidate for future clinical
      translation.

PMID- 29349489
TI  - Characterization of multiple antilisterial peptides produced by sakacin P
      producing Lactobacillus sakei subsp. sakei 2a.
AB  - Antimicrobial compounds produced by lactic acid bacteria can be explored as
      natural food biopreservatives. In a previous report, the main antimicrobial
      compounds produced by the Brazilian meat isolate Lactobacillus sakei subsp. sakei
      2a, i.e., bacteriocin sakacin P and two ribosomal peptides (P2 and P3) active
      against Listeria monocytogenes, were described. In this study, we report the
      spectrum of activity, molecular mass, structural identity and mechanism of action
      of additional six antilisterial peptides produced by Lb. sakei 2a, detected in a
      24 h-culture in MRS broth submitted to acid treatment (pH 1.5) and proper
      fractionation and purification steps for obtention of free and cell-bound
      proteins. The six peptides presented similarity to different ribosomal proteins
      of Lb. sakei subsp sakei 23K and the molecular masses varied from 4.6 to 11.0
      kDa. All peptides were capable to increase the efflux of ATP and decrease the
      membrane potential in Listeria monocytogenes. The activity of a pool of the
      obtained antilisterial compounds [enriched active fraction (EAF)] against
      Listeria monocytogenes in a food model (meat gravy) during refrigerated storage
      (4  degrees C) for 10 days was also tested and results indicated that the
      populations of L. monocytogenes in the food model containing the acid extract
      remained lower than those at time 0-day, evidencing that the acid extract of a
      culture of Lb. sakei 2a is a good technological alternative for the control of
      growth of L. monocytogenes in foods.

PMID- 29349490
TI  - Auto-aggregation properties of a novel aerobic denitrifier Enterobacter sp.
      strain FL.
AB  - Enterobacter sp. strain FL was newly isolated from activated sludge and exhibited
      significant capability of auto-aggregation as well as aerobic denitrification.
      The removal efficiencies of NO3--N, total nitrogen (TN), and TOC by strain FL in
      batch culture reached 94.6, 63.9, and 72.5% in 24 h, respectively. The production
      of N2O and N2 in the presence of oxygen demonstrated the occurrence of aerobic
      denitrification. The auto-aggregation index of strain FL reached 54.3%,
      suggesting a high tendency that the cells would agglomerate into aggregates. The
      production of extracellular polymeric substances (EPSs), which were mainly
      composed of proteins followed by polysaccharides, was considered to be related to
      the cell aggregation according to Fourier transform infrared (FT-IR) and confocal
      laser scanning microscopy (CLSM). The proteins in EPS were evenly and tightly
      combined to cells and altered the protein secondary structures of cell surface
      from random coils to beta-sheets and three-turn helices. The alteration of
      protein secondary structures of cell surface caused by the proteins in EPS might
      play a dominant role in the auto-aggregation of strain FL. To further assess the
      feasibility of strain FL for synthetic wastewater treatment, a sequencing batch
      reactor (SBR), solely inoculated with strain FL, was conducted. During the 16
      running cycles, the removal efficiency of NO3--N was 90.2-99.7% and the auto
      aggregation index was stabilized at 35.0-41.5%. The EPS promoted the biomass of
      strain FL to aggregate in the SBR.

PMID- 29349491
TI  - Formulation and stabilization of an Arthrobacter strain with good storage
      stability and 4-chlorophenol-degradation activity for bioremediation.
AB  - Chlorophenols are widespread and of environmental concern due to their toxic and
      carcinogenic properties. Development of less costly and less technically
      challenging remediation methods are needed; therefore, we developed a formulation
      based on micronized vermiculite that, when air-dried, resulted in a granular
      product containing the 4-chlorophenol (4-CP)-degrading Gram-positive bacterium
      Arthrobacter chlorophenolicus A6. This formulation and stabilization method
      yielded survival rates of about 60% that remained stable in storage for at least
      3 months at 4  degrees C. The 4-CP degradation by the formulated and desiccated
      A. chlorophenolicus A6 cells was compared to that of freshly grown cells in
      controlled-environment soil microcosms. The stabilized cells degraded 4-CP
      equally efficient as freshly grown cells in two different set-ups using both
      hygienized and non-treated soils. The desiccated microbial product was
      successfully employed in an outdoor pot trial showing its effectiveness under
      more realistic environmental conditions. No significant phytoremediation effects
      on 4-CP degradation were observed in the outdoor pot experiment. The 4-CP
      degradation kinetics from both the microcosms and the outdoor pot trial were used
      to generate a predictive model of 4-CP biodegradation potentially useful for
      larger-scale operations, enabling better bioremediation set-ups and saving of
      resources. This study also opens up the possibility of formulating and
      stabilizing also other Arthrobacter strains possessing different desirable
      pollutant-degrading capabilities.

PMID- 29349492
TI  - Ganoderma lucidum phosphoglucomutase is required for hyphal growth,
      polysaccharide production, and cell wall integrity.
AB  - Phosphoglucomutase (pgm) is an important enzyme in carbohydrate metabolism that
      is located at the branching point between glycolysis and the Leloir pathway. pgm
      catalyzes the reversible conversion reaction between glucose-6-phosphate (Glc-6
      P) and glucose-1-phosphate (Glc-1-P). The glpgm gene was cloned in Escherichia
      coli, and the recombinant pgm protein from Ganoderma lucidum was purified in this
      study. The activity of native pgm was also detected to demonstrate that this
      predicted gene was functional in G. lucidum. Interestingly, silencing the glpgm
      gene in the fungus reduced hyphal growth. Moreover, glpgm silencing was
      associated with declining extracellular polysaccharide (EPS) production
      (approximately 20-40% of that in the WT strain) and increasing intracellular
      polysaccharide (IPS) production (approximately 1.7-fold that in the WT strain).
      Additionally, in our research, cell wall components were also shown to differ
      according to the glpgmi strain. Compared with WT, chitin significantly increased
      by 1.5-fold; however, the content of beta-1,3-glucan was observably reduced to 60
      70% that of the WT. Further research showed that the cell wall component changes
      were associated with the transcription of related genes. These findings provide
      references for further study on the potential physiological function of pgm in G.
      lucidum.

PMID- 29349493
TI  - Biotic elicitation of ginsenoside metabolism of mutant adventitious root culture
      in Panax ginseng.
AB  - Biotic elicitation is an important biotechnological strategy for triggering the
      accumulation of secondary metabolites in adventitious root cultures. These biotic
      elicitors can be obtained from safe, economically important strains of bacteria
      found in the rhizosphere and fermented foods. Here, we assayed the effects of
      filtered cultures of five nitrogen-fixing bacteria and four types of fermentation
      bacteria on mutant adventitious Panax ginseng root cultures induced in a previous
      study by colchicine treatment. The biomass, pH, and electrical conductivity (EC)
      of the culture medium were altered at 5 days after treatment with bacteria. The
      saponin content was highest in root cultures treated with Mesorhizobium amorphae
      (GS3037), with a concentration of 105.58 mg g-1 dry weight saponin present in
      these cultures versus 74.48 mg g-1 dry weight in untreated root cultures. The
      accumulation of the ginsenosides Rb2 and Rb3 dramatically increased (19.4- and
      4.4-fold, and 18.8- and 4.8-fold) 5 days after treatment with M. amorphae
      (GS3037) and Mesorhizobium amorphae (GS336), respectively. Compound K production
      increased 1.7-fold after treatment with M. amorphae (GS3037) compared with
      untreated root cultures. These results suggest that treating mutant adventitious
      root cultures with biotic elicitors represents an effective strategy for
      increasing ginsenoside production in Panax ginseng.

PMID- 29349494
TI  - Light scattering on PHA granules protects bacterial cells against the harmful
      effects of UV radiation.
AB  - Numerous prokaryotes accumulate polyhydroxyalkanoates (PHA) in the form of
      intracellular granules. The primary function of PHA is the storage of carbon and
      energy. Nevertheless, there are numerous reports that the presence of PHA
      granules in microbial cells enhances their stress resistance and fitness when
      exposed to various stress factors. In this work, we studied the protective
      mechanism of PHA granules against UV irradiation employing Cupriavidus necator as
      a model bacterial strain. The PHA-accumulating wild type strain showed
      substantially higher UV radiation resistance than the PHA non-accumulating
      mutant. Furthermore, the differences in UV-Vis radiation interactions with both
      cell types were studied using various spectroscopic approaches (turbidimetry,
      absorption spectroscopy, and nephelometry). Our results clearly demonstrate that
      intracellular PHA granules efficiently scatter UV radiation, which provides a
      substantial UV-protective effect for bacterial cells and, moreover, decreases the
      intracellular level of reactive oxygen species in UV-challenged cells. The
      protective properties of the PHA granules are enhanced by the fact that granules
      specifically bind to DNA, which in turn provides shield-like protection of DNA as
      the most UV-sensitive molecule. To conclude, the UV-protective action of PHA
      granules adds considerable value to their primary storage function, which can be
      beneficial in numerous environments.

PMID- 29349495
TI  - Genomic-driven discovery of an amidinohydrolase involved in the biosynthesis of
      mediomycin A.
AB  - Clethramycin (1) and mediomycin A (2) belong to the linear polyene polyketide
      (LPP) family of antibiotics that exhibit potent antifungal activity. Structural
      similarities exist between 1 and 2, except that 2 contains an amino moiety
      substituted for the guanidino moiety. Herein, the draft genome sequence of
      Streptomyces mediocidicus ATCC23936, a strain which produces both 1 and 2, was
      obtained through de novo sequencing. Bioinformatic analysis of the genome
      revealed a clethramycin (cle) gene cluster that contained 25 open reading frames
      (orfs). However, amidinohydrolase for 2 formation was not found in the cle gene
      cluster. Further genomic analysis revealed an amidinohydrolase MedX, which can
      hydrolyse the guanidino form (1) into the amino form (2) via heterologous co
      expression of the cle cluster in Streptomyces lividans or by in vitro catalysis.
      These results also suggest the feasibility of engineering novel LPPs for drug
      discovery by manipulating the biosynthetic machinery of S. mediocidicus.

PMID- 29349498
TI  - Plasma metabolites associated with type 2 diabetes in a Swedish population: a
      case-control study nested in a prospective cohort.
AB  - AIMS/HYPOTHESIS: The aims of the present work were to identify plasma metabolites
      that predict future type 2 diabetes, to investigate the changes in identified
      metabolites among individuals who later did or did not develop type 2 diabetes
      over time, and to assess the extent to which inclusion of predictive metabolites
      could improve risk prediction. METHODS: We established a nested case-control
      study within the Swedish prospective population-based Vasterbotten Intervention
      Programme cohort. Using untargeted liquid chromatography-MS metabolomics, we
      analysed plasma samples from 503 case-control pairs at baseline (a median time of
      7 years prior to diagnosis) and samples from a subset of 187 case-control pairs
      at 10 years of follow-up. Discriminative metabolites between cases and controls
      at baseline were optimally selected using a multivariate data analysis pipeline
      adapted for large-scale metabolomics. Conditional logistic regression was used to
      assess associations between discriminative metabolites and future type 2
      diabetes, adjusting for several known risk factors. Reproducibility of identified
      metabolites was estimated by intra-class correlation over the 10 year period
      among the subset of healthy participants; their systematic changes over time in
      relation to diagnosis among those who developed type 2 diabetes were investigated
      using mixed models. Risk prediction performance of models made from different
      predictors was evaluated using area under the receiver operating characteristic
      curve, discrimination improvement index and net reclassification index. RESULTS:
      We identified 46 predictive plasma metabolites of type 2 diabetes. Among novel
      findings, phosphatidylcholines (PCs) containing odd-chain fatty acids (C19:1 and
      C17:0) and 2-hydroxyethanesulfonate were associated with the likelihood of
      developing type 2 diabetes; we also confirmed previously identified predictive
      biomarkers. Identified metabolites strongly correlated with insulin resistance
      and/or beta cell dysfunction. Of 46 identified metabolites, 26 showed
      intermediate to high reproducibility among healthy individuals. Moreover, PCs
      with odd-chain fatty acids, branched-chain amino acids, 3-methyl-2-oxovaleric
      acid and glutamate changed over time along with disease progression among
      diabetes cases. Importantly, we found that a combination of five of the most
      robustly predictive metabolites significantly improved risk prediction if added
      to models with an a priori defined set of traditional risk factors, but only a
      marginal improvement was achieved when using models based on optimally selected
      traditional risk factors. CONCLUSIONS/INTERPRETATION: Predictive metabolites may
      improve understanding of the pathophysiology of type 2 diabetes and reflect
      disease progression, but they provide limited incremental value in risk
      prediction beyond optimal use of traditional risk factors.

PMID- 29349499
TI  - Spatial coverage of mangrove communities in the Arabian Gulf.
AB  - Mangroves are the natural protectors of the coast, carbon sinks, and a nursery to
      many terrestrial as well as aquatic organisms. Different effects caused by
      natural forces together with anthropogenic factors have reduced mangrove cover on
      a global scale, yet little is known about the overall surface covered by
      mangroves in the Arabian Gulf. Therefore, the aim of this study was to examine
      their spatial coverage and distribution along the Gulf coastlines, using 25
      satellite imagery recently acquired from Landsat 8 data for the year 2017. This
      study found about 165 km2 of fragmented scattered mangroves, mostly intense in
      the United Arab Emirates, where plantation projects have likely played a
      significant role in increasing their cover over the years. Whereas mangrove in
      Kuwait is rare, areas like Bahrain, Qatar and Saudi Arabia remained stable with a
      slight increase. However, mangroves in Iran appear to suffer a decline throughout
      the years.

PMID- 29349502
TI  - A biomechanical comparison of different fixation techniques for fractures of the
      acetabular posterior wall.
AB  - PURPOSE: This study aimed to evaluate the biomechanical stability of different
      fixation techniques for fractures of the acetabular posterior wall. The
      hypothesis was that a reconstruction plate, combined with compression screw
      fixation and a plate placed lateral to the screws, would achieve a higher peak
      load to failure and stiffness and reduced gapping during cycle loading than other
      fixation techniques. METHODS: A total of 24 Sawbone pelvis models were created
      with simulated fractures at the posterior wall of the acetabulum. Anatomic
      reduction and internal fixation were performed randomly using one of four
      techniques: (A) reconstruction plate and compression screw fixation was placed
      with a plate medial to the screws; (B) plate and screw fixation with the plate
      located lateral to the screws; (C) plate fixation alone, and (D) screw fixation
      alone. Six models were tested in each group under cyclic and sustaining loading
      tests. Peak load to failure and stiffness were calculated from load displacement
      curves. RESULTS: Peak load to failure and stiffness in group B (3698.71 N and
      2900.48 N/mm, respectively), featuring reconstruction plate and compression screw
      fixation with the plate placed lateral to the screws, were significantly higher
      than groups C (2508.74 N, 1602.75 N/mm) and D (2332.06 N, 1454.26 N/mm). No
      statistical differences were observed when group A (2941.60 N, 2136.50 N/mm) was
      compared with the other groups. There were no significant differences in gapping
      between groups. CONCLUSIONS: Fixation using a reconstruction plate and
      compression screws placed lateral to the screws may address acetabular posterior
      wall fractures in a more appropriate manner than techniques using only plates or
      screws. However, this study does not provide evidence to support the fact that
      placing the plate lateral to the screws is advantageous in comparison with other
      techniques.

PMID- 29349500
TI  - Exogenous H2S switches cardiac energy substrate metabolism by regulating SIRT3
      expression in db/db mice.
AB  - : Hydrogen sulfide (H2S) is involved in diverse physiological functions, such as
      anti-hypertension, anti-proliferation, regulating ATP synthesis, and reactive
      oxygen species production. Sirtuin 3 (SIRT3) is a NAD + -dependent deacetylase
      that regulates mitochondrial energy metabolism. The role of H2S in energy
      metabolism in diabetic cardiomyopathy (DCM) may be related to regulate SIRT3
      expression; however, this role remains to be elucidated. We hypothesized that
      exogenous H2S could switch cardiac energy metabolic substrate preference by
      lysine acetylation through promoting the expression of SIRT3 in cardiac tissue of
      db/db mice. Db/db mice, neonatal rat cardiomyocytes, and H9c2 cell line with the
      treatment of high glucose, oleate, and palmitate were used as animal and cellular
      models of type 2 diabetes. Using LC-MS/MS, we identified 76 proteins that
      increased acetylation, including 8 enzymes related to fatty acid beta-oxidation
      and 7 enzymes of the tricarboxylic acid (TCA) cycle in the db/db mice hearts
      compared to those with the treatment of NaHS. Exogenous H2S restored the
      expression of NAMPT and the ratio of NAD+/NADH enhanced the expression and
      activity of SIRT3. As a result of activation of SIRT3, the acetylation level and
      activity of fatty acid beta-oxidation enzyme LCAD and the acetylation of glucose
      oxidation enzymes PDH, IDH2, and CS were reduced which resulted in activation of
      PDH, IDH2, and CS. Our finding suggested that H2S induced a switch in cardiac
      energy substrate utilization from fatty acid beta-oxidation to glucose oxidation
      in DCM through regulating SIRT3 pathway. KEY MESSAGES: H2S regulated the
      acetylation level and activities of enzymes in fatty acid oxidation and glucose
      oxidation in cardiac tissues of db/db mice. Exogenous H2S decreased mitochondrial
      acetylation level through upregulating the expression and activity of SIRT3 in
      vivo and in vitro. H2S induced a switch in cardiac energy substrate utilization
      from fatty acid oxidation to glucose.

PMID- 29349503
TI  - Is there any difference between open and arthroscopic treatment for
      osteochondritis dissecans (OCD) of the humeral capitellum: a systematic review
      and meta-analysis.
AB  - PURPOSE: We present a systematic review of the recent literatures regarding the
      arthroscopic and open technique in fragment fixation for osteochondritis
      dissecans (OCD) of the humeral capitellum and an analysis of the subjective and
      objective outcomes between these two procedures. METHODS: PubMed and EMBASE were
      reviewed for suitable articles relating to fragment fixation for OCD, both open
      and arthroscopic. We included all studies reporting on the clinical outcomes of
      these two procedures that were published in the English language. Data extracted
      from each study included level of evidence, number of patients, surgical
      techniques, length of follow-up, clinical outcome measures including outcome
      scores, range of motion (ROM), return to sports, osseous union and complications.
      We analyzed each study to determine the primary outcome measurement. RESULTS: A
      total of ten studies met our inclusion criteria. Among all studies, 35
      arthroscopic procedures and 107 open procedures were performed. After the
      procedure, 70 patients (86.4%) in the open group returned to their sports, and 32
      patients (91.4%) in the arthroscopic group returned to their sports. In the
      arthroscopic group, patients gained 14.1 degrees of flexion and 9.5 degrees of
      extension after surgery. In the open group, patients gained 8 degrees of flexion
      and 5.7 degrees of extension. Five patients (4.7%) had complications in the open
      group. No complication was found in the arthroscopic group. CONCLUSIONS: Both
      open and arthroscopic lesion debridement with fragment fixation are successful in
      treating unstable OCD. The arthroscopic technique may be a better choice than the
      open procedure, but we need high-level evidence to determine the superiority of
      the open or arthroscopic techniques in treating elbow OCD. LEVEL OF EVIDENCE:
      Level III.

PMID- 29349504
TI  - Oral bacterial colonization on dental implants restored with titanium or zirconia
      abutments: 6-month follow-up.
AB  - OBJECTIVE: This investigation aimed to characterize in a 6-month follow-up the
      microbial profile of implants restored with either titanium or zirconia abutments
      at the genus or higher taxonomic levels. METHODS: Twenty healthy individuals
      indicative for implant-retained single restorations were investigated. Half of
      participants were restored with titanium and half with zirconia abutments.
      Biofilm was collected from the implant-related sites after 1, 3, and 6 months of
      loading. The 16S rDNA genes were amplified and sequenced with Roche/454 platform.
      RESULTS: A total of 596 species were identified in 360 samples and grouped in 18
      phyla and 104 genera. Titanium- or zirconia-related sites as well as teeth showed
      similar total numbers of operational taxonomic units (OTUs) colonizing surfaces
      over time. Firmicutes, Proteobacteria, Fusobacteria, Bacteroidetes, and
      Actinobacteria were the most prevalent phyla with significant differences between
      different surfaces and time point. Unclassified genera were found in lower levels
      (1.71% up to 9.57%) on titanium and zirconia samples when compared with teeth,
      with no significant differences. CONCLUSION: Titanium- and zirconia-related
      surfaces are promptly colonized by a bacterial community similar to those found
      in the remaining adjacent teeth. Results suggest a selective adhesion of
      different bacterial genotypes for either titanium or zirconia surfaces. Data also
      indicate a significant interaction between the relative effects taxa, time point,
      and sampling site. CLINICAL RELEVANCE: The present study disclosed a wider
      spectrum of microorganisms colonizing either titanium- or zirconia-related
      microbiomes in very early stage of implant colonization, revealing differences
      and suggesting a probably specific mechanism for selective bacterial adhesion.

PMID- 29349505
TI  - Embracing your emotions: affective state impacts lateralisation of human
      embraces.
AB  - Humans are highly social animals that show a wide variety of verbal and non
      verbal behaviours to communicate social intent. One of the most frequently used
      non-verbal social behaviours is embracing, commonly used as an expression of love
      and affection. However, it can also occur in a large variety of social situations
      entailing negative (fear or sadness) or neutral emotionality (formal greetings).
      Embracing is also experienced from birth onwards in mother-infant interactions
      and is thus accompanying human social interaction across the whole lifespan.
      Despite the importance of embraces for human social interactions, their
      underlying neurophysiology is unknown. Here, we demonstrated in a well-powered
      sample of more than 2500 adults that humans show a significant rightward bias
      during embracing. Additionally, we showed that this general motor preference is
      strongly modulated by emotional contexts: the induction of positive or negative
      affect shifted the rightward bias significantly to the left, indicating a
      stronger involvement of right-hemispheric neural networks during emotional
      embraces. In a second laboratory study, we were able to replicate both of these
      findings and furthermore demonstrated that the motor preferences during embracing
      correlate with handedness. Our studies therefore not only show that embracing is
      controlled by an interaction of motor and affective networks, they also
      demonstrate that emotional factors seem to activate right-hemispheric systems in
      valence-invariant ways.

PMID- 29349506
TI  - New perspectives on human multitasking.

PMID- 29349507
TI  - Closing the gap: connecting sudden representational change to the subjective Aha!
      experience in insightful problem solving.
AB  - : Two hallmarks of insightful problem solving are thought to be suddenness in the
      emergence of solution due to changes in problem representation, and the
      subjective Aha! EXPERIENCE: Although a number of studies have explored the Aha!
      experience, few studies have attempted to measure representational change.
      Following the lead of Durso et al. (Psychol Sci 5(2):94-97, 1994) and Cushen and
      Wiley (Conscious Cognit 21(3):1166-1175, 2012), in this study, participants made
      importance-to-solution ratings throughout their solution attempts as a way to
      assess representational change. Participants viewed a set of magic trick videos
      with the task of finding out how each trick worked, and rated six action verbs
      for each trick (including one that implied the correct solution) multiple times
      during solution. They were also asked to indicate the extent to which they
      experienced an Aha! moment. Patterns of ratings that showed a sudden change
      towards a correct solution led to stronger Aha! experiences than patterns that
      showed a more incremental change towards a correct solution, or a change towards
      incorrect solutions. The results show a connection between sudden changes in
      problem representations (leading to correct solutions) and the subjective
      appraisal of solutions as an Aha! EXPERIENCE: This offers the first empirical
      support for a close relationship between two theoretical constructs that have
      traditionally been assumed to be related to insightful problem solving.

PMID- 29349508
TI  - Impact of intervention time on hospital survival in patients requiring emergent
      airway management: a preliminary study.
AB  - BACKGROUND: The time in the day of intervention for physiological deterioration
      reportedly impacts patient outcomes. This study aimed at determining the impact
      of the time of ETI on hospital survival in critically ill patients. METHODS:
      Between January 2014 and December 2016, 151 patients who underwent emergency
      tracheal intubation (ETI) by the airway response team (ART) in the general wards
      of a tertiary referral center were retrospectively reviewed. Patients were
      divided into two groups based on the time of ETI (daytime group, 8:00 a.m.-4:00
      p.m., n = 57, mean age 63.5 +/- 14.1 years; nighttime group, 4:00 p.m.-8:00 a.m.,
      n = 94, mean age 60.4 +/- 14.9 years). Data regarding demographic information,
      comorbidities, trigger events for intubation, survival-to-discharge rates, acute
      physiology and chronic health evaluation II (APACHE II), ventilator-free days,
      and airway techniques were collected. RESULTS: There was no significant
      difference in sex, age, body mass index, APACHE II, or comorbidities between the
      two groups, except that a higher proportion of patients presented with
      arrhythmias (21.1 vs. 8.5%, p = 0.028) and received fiberoptic intubation (24.6
      vs. 11.7%, p = 0.039) in the daytime group than in the nighttime group. The time
      of the ART arrival after call was also shorter in daytime than that in nighttime
      (6.1 +/- 1.4 vs. 10.5 +/- 3.2 min, respectively, p < 0.001). There were no
      differences in the survival-to-discharge rate (45.6 vs. 43.6%, p = 0.811),
      ventilator-free days, or trigger events between the two groups. CONCLUSIONS:
      Emergent tracheal intubation in the nighttime may not have negative impact on the
      survival-to-discharge rate compared with that performed in the daytime.

PMID- 29349509
TI  - Complex issues in new ultrasound-guided nerve blocks: how to name, where to
      inject, and how to publish.
AB  - The recent development of ultrasound-guide nerve block has led to innovation in
      anesthesia and pain clinics. However, it has also led to some complex issues,
      including (1) how to name a new technique, (2) the appropriateness of an
      intramuscular approach, and (3) how to publicize a new technique. This review
      addresses naming strategy, feasibility of intramuscular approach block, and
      methods of publication. First, researchers and authors should pay attention to
      appropriate nomenclature for the term 'approach', 'compartment block', and 'nerve
      block' for a new block. Second, it is lack of evidences to facilitate muscle
      injection, and adequate preparation and adherence to proper technique for
      intramuscular approach block should be considered; confirmation of abnormal signs
      at the injection area, use of a thin needle and the lowest concentration and
      volume of local anesthetic without supplementation with steroid or epinephrine,
      compressing hemostasis, and sufficient interval of the blocks. Third, adequate
      dissemination of information would also be necessary through publication in
      appropriate media. We hope this review boost reasonable development of nerve
      block.

PMID- 29349510
TI  - Uncertain effect of preventative shoulder rehabilitation for patients who
      underwent total laryngectomy with neck dissection.
AB  - INTRODUCTION: Total laryngectomy (TL) with neck dissection (ND) is considered as
      crucial management for advanced-stage of laryngeal cancer. Shoulder dysfunction
      has long been recognized as a potential complication resulting from neck
      dissection. The aim of this study was to evaluate the effect of early
      prophylactic rehabilitation program in patients who underwent TL with ND.
      METHODS: A prospective, nonrandomized design was used. Seventy-six participants
      who underwent TL with ND were assigned into either an intervention or a control
      group. The control group received current standard care with no formal shoulder
      exercise provided, while the intervention group attended early preventive
      rehabilitation lasting 12 weeks. Participants were assessed at baseline, and at 3
      and 6 months after surgery. Measured outcomes included shoulder function and
      patient-reported quality of life. General linear models with repeated measures
      were used to examine outcome changes in both groups over the designated
      assessment intervals. RESULTS: Improvement in shoulder function and patient
      reported quality of life were both statistically significant over time, with no
      significant difference between control or intervention groups, indicating little
      or no benefit of preventative intervention on shoulder function outcomes.
      Analysis involving five subscales and the summary score of the quality of life
      questionnaire had only statistically significant improvement over time for both
      the control or intervention groups, except for physical well-being domain which
      had statistical significance both over time and between the control and
      intervention groups. CONCLUSION: In this study, preventative exercise program
      initiated immediately after surgery had a limited impact on both shoulder
      function and perceived quality of life.

PMID- 29349511
TI  - Treatment of severe periodontitis with a laser and light-emitting diode (LED)
      procedure adjunctive to scaling and root planing: a double-blind, randomized,
      single-center, split-mouth clinical trial investigating its efficacy and patient
      reported outcomes at 1 year.
AB  - Broad methodological heterogeneity makes the literature on the clinical effects
      of laser treatment in periodontitis, both as monotherapy and adjunct to non
      surgical therapy, which is difficult to interpret. The present split-mouth study
      was performed: (i) to determine the efficacy and safety of a photoablative
      photodynamic diode laser therapy, including antiseptic LED irradiation, in
      adjunct to scaling and root planing (iPAPD+SRP) vs. sham-treatment+SRP for the
      treatment of diffuse severe periodontitis and (ii) to estimate the patient
      reported outcomes. Twenty-four patients with severe periodontitis were treated
      with iPAPD+SRP or sham-treatment+SRP. iPAPD+SRP consisted of the following: (1)
      intra-/extra-pocket de-epithelization with photoablative lambda 810 nm laser, (2)
      disinfection with lambda 405 nm LED, (3) SRP, and (4) 10 weekly antiseptic/anti
      inflammatory photodynamic treatments with lambda 635 nm laser and 0.1% toluidine
      blue as photosensitizer. Clinical and cytofluorescent periodontal markers and
      patient-reported results were analyzed. At 1-year follow-up, both groups showed a
      significant reduction of several severity markers of periodontitis, namely
      probing depth (PD) and bleeding on probing (BoP), as well as of bacteria,
      polymorphonuclear cells, erythrocytes and damaged epithelial cells in exfoliative
      samples, as compared with day 0. The quadrants subjected to iPAPD+SRP showed
      significantly better values of these parameters as well as of clinical attachment
      level (CAL) as compared with those undergoing sham-treatment+SRP. The patients'
      perceived pain/discomfort, and overall liking was also in favor of the iPAPD+SRP
      treatment. This study confirms the efficacy of combined phototherapy in adjunct
      to SRP which had emerged from previous clinical trials, extending its field of
      application to severe periodontitis.

PMID- 29349512
TI  - Photobiomodulation induces in vitro re-epithelialization via nitric oxide
      production.
AB  - Photobiomodulation is a widely used tool in regenerative medicine thanks to its
      ability to modulate a plethora of physiological responses. Wound re
      epithelialization is strictly regulated by locally produced chemical mediators,
      such as nitric oxide (NO), a highly reactive free radical generated by the nitric
      oxide synthase (NOS) enzymatic family. In this study, it has been hypothesized
      that a 980-nm low-level laser stimulation could increase NO production in human
      keratinocytes and that such event might be directly related to the re
      epithelialization process. Human keratinocytes were irradiated with increasing
      energy outputs (10-75 J) in the absence or presence of L-NAME, a NOS inhibitor.
      Laser stimulation induced an increase in NO production, resulting in an energy
      dependent increase in both keratinocytes proliferation and re-epithelialization
      ability. The direct link between increased NO production and the observed
      physiological responses was confirmed by their inhibition in L-NAME pre-treated
      samples. Since NO production increase is a quick event, it is conceivable that it
      is due to an increase in existing NOS activity rather than to a de novo protein
      synthesis. For this reason, it could be hypothesized that photobiomodulation
      derived NO positive effects on keratinocytes behavior might rely on a near
      infrared mediated increase in NOS conformational stability and cofactors as well
      as substrate binding ability, finally resulting in an increased enzymatic
      activity.

PMID- 29349513
TI  - 3D-QSAR study of steroidal and azaheterocyclic human aromatase inhibitors using
      quantitative profile of protein-ligand interactions.
AB  - Aromatase is a member of the cytochrome P450 superfamily responsible for a key
      step in the biosynthesis of estrogens. As estrogens are involved in the control
      of important reproduction-related processes, including sexual differentiation and
      maturation, aromatase is a potential target for endocrine disrupting chemicals as
      well as breast cancer therapy. In this work, 3D-QSAR combined with quantitative
      profile of protein-ligand interactions was employed in the identification and
      characterization of critical steric and electronic features of aromatase
      inhibitor complexes and the estimation of their quantitative contribution to
      inhibition potency. Bioactivity data on pIC50 values of 175 steroidal and 124
      azaheterocyclic human aromatase inhibitors (AIs) were used for the 3D-QSAR
      analysis. For the quantitative description of the effects of the hydrophobic
      contact and nitrogen-heme-iron coordination on aromatase inhibition, the
      hydrophobicity density field model and the smallest dual descriptor Deltaf(r) S
      were introduced, respectively. The model revealed that hydrophobic contact and
      nitrogen-heme-iron coordination primarily determines inhibition potency of
      steroidal and azaheterocyclic AIs, respectively. Moreover, hydrogen bonds with
      key amino acid residues, in particular Asp309 and Met375, and interaction with
      the heme-iron are required for potent inhibition. Phe221 and Thr310 appear to be
      quite flexible and adopt different conformations according to a substituent at 4-
      or 6-position of steroids. Flexible docking results indicate that proper
      representation of the residues' flexibility is critical for reasonable
      description of binding of the structurally diverse inhibitors. Our results
      provide a quantitative and mechanistic understanding of inhibitory activity of
      steroidal and azaheterocyclic AIs of relevance to adverse outcome pathway
      development and rational drug design.

PMID- 29349514
TI  - NB-UVB irradiation downregulates keratin-17 expression in keratinocytes by
      inhibiting the ERK1/2 and STAT3 signaling pathways.
AB  - Keratin-17 (K17) is a cytoskeletal protein produced by keratinocytes (KCs), which
      is overexpressed in psoriasis and may play a pivotal role in its pathogenesis.
      Narrow-band ultraviolet B (NB-UVB) irradiation is used as a general treatment for
      psoriasis, although its impact on K17 expression has yet to be determined. In
      this study, we aimed to investigate the effect of NB-UVB irradiation on K17
      expression and its signaling pathways. After exposure to NB-UVB irradiation,
      immortalized human keratinocytes (HaCaT cells) were analyzed by flow cytometry,
      CCK-8 assays and transmission electron microscopy to examine proliferation.
      Meanwhile, K17 expression in primary human epithelial keratinocytes was detected
      by quantitative real-time polymerase chain reaction (qRT-PCR), western blot
      analysis and immunofluorescence. HaCaT cells pre-incubated with PD-98059 and
      piceatannol were subjected to western blot analysis to examine ERK1/2 and STAT3
      phosphorylation. The ears of mice treated with imiquimod (IMQ) and irradiated by
      NB-UVB were taken to examine K17 expression by qRT-PCR, western blot analysis,
      and immunofluorescence. Our results showed that 400 mJ/cm2 of NB-UVB irradiation
      was the maximum tolerable dose for HaCaT cells and could cause inhibited HaCaT
      cell proliferation and moderate increase of the early apoptosis. Furthermore, NB
      UVB irradiation could downregulate K17 expression by inhibiting the ERK1/2 and
      STAT3 signaling pathways. In experiments conducted in vivo, NB-UVB irradiation
      with doses of MED or higher could eliminate the IMQ-induced psoriasis-like
      dermatitis and inhibit K17 expression. These results indicated that NB-UVB
      irradiation may eliminate chronic psoriatic plaques by suppressing K17 expression
      via the ERK1/2 and STAT3 signaling pathways.

PMID- 29349515
TI  - Matrix metalloproteinase-2 and -9 activity levels increase in cutaneous lupus
      erythematosus lesions and correlate with disease severity.
AB  - Lupus erythematosus is a chronic autoimmune disease characterized by remissions
      and exacerbations. Accumulated evidence indicated that matrix metalloproteinases
      (MMPs) are upregulated in inflammatory cells of cutaneous lupus erythematosus
      (CLE); however, the activity levels of these proteases have remained
      uncharacterized. To elucidate the significance of MMP-2, MMP-9, and TIMP-1 in CLE
      pathogenesis, gelatin zymography was used to investigate pro and active levels of
      MMP-2 and MMP-9 in lesional and perilesional skin biopsies obtained from twenty
      two CLE patients. TIMP-1 protein levels were detected by ELISA in the biopsy
      specimens. The correlation between biochemical parameters and clinical
      characteristics of the disease was also evaluated. Significantly higher levels of
      active MMP-2, active MMP-9, proMMP-9, active/proMMP-2, and TIMP-1 were detected
      in lesional skin samples. Besides, the active/proMMP-9 was elevated in female and
      smoking patients. Active MMP-9 levels and active/proMMP-9 were also increased in
      elderly patients. Active MMP-9 levels were lower in patients who had smaller
      total damage score. Consistently, active/proMMP-9 and active/proMMP-2 were
      positively correlated with CLASI. Interestingly, in hydroxychloroquine or topical
      corticosteroid-treated patients, MMP-2/-9 activity levels were found to be higher
      compared to untreated patients. These findings suggest that increased MMP-2 and
      MMP-9 activities may contribute to the pathogenesis of CLE and cutaneous disease
      severity.

PMID- 29349516
TI  - New perspectives in the history of twentieth-century life sciences: historical,
      historiographical and epistemological themes.
AB  - The history of twentieth-century life sciences is not exactly a new topic.
      However, in view of the increasingly rapid development of the life sciences
      themselves over the past decades, some of the well-established narratives are
      worth revisiting. Taking stock of where we stand on these issues was the aim of a
      conference in 2015, entitled "Perspectives for the History of Life Sciences"
      (Munich, Oct 30-Nov 1, 2015). The papers in this topical collection are based on
      work presented and discussed at and around this meeting. Just as the conference,
      the collection aims at exploring fields in the history of life sciences that
      appear understudied, sources that have been overlooked, and novel ways of
      engaging with this material. The papers convened in this collection may not be
      representative of the field as a whole; but we feel that they do indicate some
      elements that have received emphasis in recent years, and may become more central
      in the years to come, such as the history of previously neglected contexts and
      domains of the life sciences, the question of continuity and change on the level
      of practices, the history of complexity and diversity in twentieth-century life
      sciences and the reconsideration of the relationship between history and
      philosophy of life sciences.

PMID- 29349517
TI  - A novel genomic signature predicting FDG uptake in diverse metastatic tumors.
AB  - BACKGROUND: Building a universal genomic signature predicting the intensity of
      FDG uptake in diverse metastatic tumors may allow us to understand better the
      biological processes underlying this phenomenon and their requirements of glucose
      uptake. METHODS: A balanced training set (n = 71) of metastatic tumors including
      some of the most frequent histologies, with matched PET/CT quantification
      measurements and whole human genome gene expression microarrays, was used to
      build the signature. Selection of microarray features was carried out exclusively
      on the basis of their strong association with FDG uptake (as measured by
      SUVmean35) by means of univariate linear regression. A thorough bioinformatics
      study of these genes was performed, and multivariable models were built by
      fitting several state of the art regression techniques to the training set for
      comparison. RESULTS: The 909 probes with the strongest association with the
      SUVmean35 (comprising 742 identifiable genes and 62 probes not matched to a
      symbol) were used to build the signature. Partial least squares using three
      components (PLS-3) was the best performing model in the training dataset cross
      validation (root mean square error, RMSE = 0.443) and was validated further in an
      independent validation dataset (n = 13) obtaining a performance within the 95% CI
      of that obtained in the training dataset (RMSE = 0.645). Significantly
      overrepresented biological processes correlating with the SUVmean35 were
      identified beyond glycolysis, such as ribosome biogenesis and DNA replication
      (correlating with a higher SUVmean35) and cytoskeleton reorganization and
      autophagy (correlating with a lower SUVmean35). CONCLUSIONS: PLS-3 is a signature
      predicting accurately the intensity of FDG uptake in diverse metastatic tumors.
      FDG-PET might help in the design of specific targeted therapies directed to
      counteract the identified malignant biological processes more likely activated in
      a tumor as inferred from the SUVmean35 and also from its variations in response
      to antineoplastic treatments.

PMID- 29349519
TI  - Agonistic autoantibodies against adrenergic receptors correlating with
      antihypertensive therapy in long-standing diabetes type 2.

PMID- 29349518
TI  - Checkpoint Inhibitors, Palliative Care, or Hospice.
AB  - PURPOSE: Checkpoint (CTLA-4, PD-1, and PD-L1) inhibitors have changed the face of
      oncology. A subset of patients enjoys long, gratifying treatment responses.
      Unfortunately, most patients do not respond even when expressing favorably
      markers such as PD-L1. Checkpoint inhibitors are largely palliative (though a
      subset have long-term cancer responses) and as such patient-related outcome
      measures should be included when evaluating benefits. The purpose of this review
      is to place checkpoint inhibitor trials within a palliation context. Included is
      a discussion on potential adverse effects on end-of-life care. RECENT FINDINGS:
      Pivotal studies have presented efficacy and safety data but we have little
      published data on quality of life or symptom responses. Extension of life is
      approximately 2-3 months with some long-term responses in a minority of patients.
      The cost of checkpoint inhibitors is high for utility (as measured by quality
      adjusted life-year saved) and ranges from 81,000 to over 200,000 USD for quality
      adjusted life-year saved. Adverse effects were suboptimally reported in multiple
      studies. Meaningful responses in many trials as defined by the European Society
      of Medical Oncology are modest. Because at least for now, checkpoint inhibitors
      are used in advanced cancer and largely palliative patients should be seen by
      palliative specialists, symptoms related to cancer assessed, and advanced
      directives addressed. Treatment-related autoimmune diseases represent toxicities
      which oncologists and palliative specialists must understand. This means that
      palliative care specialists should know about the benefits and adverse effects of
      these agents. Whether checkpoint inhibitors increase or decrease aggressive care,
      hospice referrals, and costs at the end of life is yet to be determined.

PMID- 29349520
TI  - Experimental Study of 5-fluorouracil Encapsulated Ethosomes Combined with CO2
      Fractional Laser to Treat Hypertrophic Scar.
AB  - OBJECTIVE: This study is designed to explore permeability of ethosomes
      encapsulated with 5-florouracil (5-FU) mediated by CO2 fractional laser on
      hypertrophic scar tissues. Moreover, therapeutic and duration effect of CO2
      fractional laser combined with 5-FU encapsulated ethosomes in rabbit ear
      hypertrophic scar model will be evaluated. METHODS: The permeated amount of 5-FU
      and retention contents of 5-FU were both determined by high-performance liquid
      chromatography (HPLC). Fluorescence intensities of ethosomes encapsulated with 5
      FU (5E) labeled with Rodanmin 6GO (Rho) were measured by confocal laser scanning
      microscopy (CLSM). The permeability promotion of 5E labeled with Rho in rabbit
      ear hypertrophic scar mediated by CO2 fractional laser was evaluated at 0 h, 6 h,
      12 h, 24 h, 3 days and 7 days after the irradiation. The opening rates of the
      micro-channels were calculated according to CLSM. The therapeutic effect of 5EL
      was evaluated on rabbit ear hypertrophic scar in vivo. Relative thickness of
      rabbit ear hypertrophic scar before and after the treatment was measured by
      caliper method. Scar elevation index (SEI) of rabbit ear hypertrophic scar was
      measured using H&E staining. RESULTS: The data showed that the penetration amount
      of 5EL group was higher than 5E group (4.15 +/- 2.22 vs. 0.73 +/- 0.33; p < 0.05)
      after 1-h treatment. Additionally, the penetration amount of 5EL was higher than
      that of the 5E group (107.61 +/- 13.27 vs. 20.73 +/- 3.77; p < 0.05) after 24-h
      treatment. The retention contents of the 5EL group also showed higher level than
      5E group (24.42 +/- 4.37 vs.12.25 +/- 1.64; p < 0.05). The fluorescence intensity
      of Rho in hypertrophic scar tissues of the 5EL group was higher than that of the
      5E group at different time points (1, 6, and 24 h). The opening rates of the
      micro-channels were decreased gradually within 24 h, and micro-channels were
      closed completely 3 days after the irradiation by CO2 fractional laser. The
      relative thickness and SEI of rabbit ear hypertrophic scar after 7 days of
      treatment in the 5EL group were significantly lower than the 5E group.
      CONCLUSION: CO2 fractional laser combined with topical 5E can be effective in the
      treatment of hypertrophic scar in vivo and supply a novel therapy method for
      human hypertrophic scar.

PMID- 29349521
TI  - Recent developments in the synthesis and applications of dihydropyrimidin-2(1H)
      ones and thiones.
AB  - Dihydropyrimidin-2(1H)-ones/thiones (DHPMs) are important heterocyclic compounds
      owing to their excellent biological activities and have been widely utilized in
      pharmaceutical applications. Recently, numerous DHPM derivatives have been
      prepared. This review covers the synthesis of DHPMs and improved procedures for
      the preparation of DHPMs from 1995 to 2016.

PMID- 29349523
TI  - Prognostic factors of pediatric glaucoma: a retrospective study.
AB  - PURPOSE: To correlate the features of certain types of infantile glaucoma with
      the progression and the prognosis of the disease, highlighting probable risk
      factors. METHODS: Seventy-six patients with pediatric glaucoma were recruited in
      this retrospective study. All patients underwent ophthalmological examination in
      the Department of Ophthalmology of the Saarland University Medical Center from
      January 2001 to December 2012. Our pediatric patients were classified into four
      different categories of glaucoma: (1) primary congenital glaucoma (presenting
      buphthalmus), (2) aniridia-related glaucoma, (3) Peters/Rieger's anomaly-related
      glaucoma and (4) congenital cataract-related glaucoma. Personal data comprised
      age, sex, nationality, systemic diseases and gestational age. The best-corrected
      visual acuity (BCVA), the cup-disk ratio (CDR), the intraocular pressure (IOP),
      the corneal diameter and thickness, along with the Haab striae and corneal haze,
      were recorded. RESULTS: The majority of the children were male (58%) and suffered
      from aniridia-related glaucoma (38%). Children with aniridia exhibited the worst
      BCVA. The CDR and IOP were significantly higher in children with primary
      congenital glaucoma, compared to the other groups, at the first visit. Those
      children also were with the largest corneal diameter and prevalence of Haab
      striae compared to the rest groups, whereas corneal haze was found more often and
      was more pronounced in children with Peters/Rieger's syndrome. CONCLUSIONS: We
      concluded that glaucoma was earlier detected in children with primary congenital
      glaucoma, who exhibited increased corneal diameter and high percentage of Haab
      striae comparing to the other groups. However, these children responded
      successfully to any therapeutic intervention, exhibiting better BCVA and IOP
      values than the rest groups at the second visit.

PMID- 29349522
TI  - Team-Based Care with Pharmacists to Improve Blood Pressure: a Review of Recent
      Literature.
AB  - PURPOSE OF REVIEW: We review studies published since 2014 that examined team
      based care strategies and involved pharmacists to improve blood pressure (BP). We
      then discuss opportunities and challenges to sustainment of team-based care
      models in primary care clinics. RECENT FINDINGS: Multiple studies presented in
      this review have demonstrated that team-based care including pharmacists can
      improve BP management. Studies highlighted the cost-effectiveness of a team-based
      pharmacy intervention for BP control in primary care clinics. Little information
      was found on factors influencing sustainability of team-based care interventions
      to improve BP control. Future work is needed to determine the best populations to
      target with team-based BP programs and how to implement team-based approaches
      utilizing pharmacists in diverse clinical settings. Future studies need to not
      only identify unmet clinical needs but also address reimbursement issues and
      stakeholder engagement that may impact sustainment of team-based care
      interventions.

PMID- 29349524
TI  - [Qualification and classification of medical apps : What should be noted and what
      is BfArM's contribution?]
AB  - Smartphones and tablets with their nearly unlimited number of different
      applications have become an integral part of everyday life. Thus, mobile devices
      and applications have also found their way into the healthcare sector.For
      developers, manufacturers, or users as well, it is often difficult to decide
      whether a mobile health application is a medical device.In this context, it is
      extremely important for manufacturers to decide at an early stage of the
      development whether the product is to be introduced into the market as a medical
      device and is therefore subject to the legislation on medical devices.This
      article first presents the regulatory framework and subsequently introduces the
      reader to the Federal Institute for Drugs and Medical Devices' (BfArM) view of
      the criteria for differentiating between apps as non-medical products and apps as
      medical apps as well as the classification thereof. Various examples are
      presented to demonstrate how these criteria are applied practically and options
      that support developers and manufacturers in their decision making are shown. The
      article concludes with a reference to current developments and offers a
      perspective on the new European medical device regulations MDR/IVDR (Medical
      Device Regulation/In-Vitro Diagnostic Regulation) as well as on future challenges
      regarding medical apps.

PMID- 29349525
TI  - Value of CT pulmonary angiography to predict short-term outcome in patient with
      pulmonary embolism.
AB  - To evaluate the role of CT pulmonary angiography (CTPA) in the assessment of
      pulmonary embolism (PE) severity and the related CT cardiac changes, reflecting
      the clinical status of the patients and predicting the outcome. A prospective
      study of 184 patients presented with suspicious acute PE. All patients underwent
      CTPA followed by ECHO. Pulmonary artery obstructive index (PAOI) using Qanadli
      Score was calculated and cardiac changes recorded. The patients' outcome was
      followed up for 30 days. Only 150 patients completed the study; 26.7% needed ICU
      admission while 13.3% died during follow-up. There was a significant relationship
      between the PAOI and the risk classification, right ventricular dysfunction (RVD)
      diagnosed by ECHO and the patients' short outcome. We found PAOI cut off value
      45% for mortality and 35% for ICU admission and 27.5% for RVD with 60, 75 and 90%
      sensitivity and 80, 73.3 and 68.6% specificity respectively. CT RV/LV ratio was
      the most sensitive parameter to predict RV dysfunction followed by pulmonary
      artery diameter. CTPA is not only used for diagnosis but also to assess the
      severity of PE, the effect on the right ventricular function and subsequently the
      need for ICU admission and prediction of the outcome.

PMID- 29349526
TI  - Normal pulmonary artery and branch pulmonary artery sizes in children.
AB  - To establish standards for pulmonary artery and branch pulmonary artery (PA and
      BPA) effective diameter (ED) and cross-sectional area (CSA) by using computed
      tomography (CT) data in children of a wide range of sizes and investigate the
      roundness of arteries. The ED (average of short and long axes) and CSA for the PA
      and BPA were measured using 1-mm collimation double-oblique reconstructions.
      Ordinary least squares regression was used to investigate models with various
      functional forms that related ED and CSA to patient size. Aspect ratio (AR), the
      short axis divided by long axis, was measured to evaluate roundness. The ideal
      diameter derived from CSA measurements was compared to ED, short axis, and long
      axis measurements. 108 CT examinations were analyzed in children without reason
      for abnormal PA size who ranged in age from 0 to 18 years (mean, 10.9 years; SD,
      5.9 years). Interrater reliability was excellent. Data were modeled using a
      natural log-transformed response variable and a linear term for height as the
      independent variable. AR for the PA, right pulmonary artery, and left pulmonary
      artery measured < 0.9 for 38, 55, and 37%, respectively, indicating that many
      arteries are not round. Ideal diameter was not significantly different than ED
      but was for short- and long-axis diameter measurements. Normal ED and CSA for PA
      and BPA were determined for children of different sizes. Measurements outside of
      the normal range are consistent with dilatation or stenosis. Single diameter
      techniques are likely to introduce error.

PMID- 29349527
TI  - Genetic Test Reporting and Counseling for Melanoma Risk in Minors May Improve Sun
      Protection Without Inducing Distress.
AB  - Genetic testing of minors is advised only for conditions in which benefits of
      early intervention outweigh potential psychological harms. This study
      investigated whether genetic counseling and test reporting for the CDKN2A/p16
      mutation, which confers highly elevated melanoma risk, improved sun protection
      without inducing distress. Eighteen minors (Mage = 12.4, SD = 1.9) from melanoma
      prone families completed measures of protective behavior and distress at
      baseline, 1 week (distress only), 1 month, and 1 year following test disclosure.
      Participants and their mothers were individually interviewed on the psychological
      and behavioral impact of genetic testing 1 month and 1 year post-disclosure.
      Carriers (n = 9) and noncarriers (n = 9) reported significantly fewer sunburns
      and a greater proportion reported sun protection adherence between baseline and 1
      year post-disclosure; results did not vary by mutation status. Anxiety symptoms
      remained low post-disclosure, while depressive symptoms and cancer worry
      decreased. Child and parent interviews corroborated these findings. Mothers
      indicated that genetic testing was beneficial (100%) because it promoted risk
      awareness (90.9%) and sun protection (81.8%) without making their children scared
      (89.9%); several noted their child's greater independent practice of sun
      protection (45.4%). In this small initial study, minors undergoing CDKN2A/p16
      genetic testing reported behavioral improvements and consistently low distress,
      suggesting such testing may be safely implemented early in life, allowing greater
      opportunity for risk-reducing lifestyle changes.

PMID- 29349528
TI  - Steps to Getting Your Manuscript Published in a High-Quality Medical Journal.
AB  - Publication of your research represents the culmination of your scientific
      activities. The key to getting manuscripts accepted is to make them
      understandable and informative so that your colleagues will read and benefit from
      them. We describe key criteria for acceptance of manuscripts and outline a multi
      step process for writing the manuscript. The likelihood that a manuscript will be
      accepted by a major journal is significantly increased if the manuscript is
      written in polished and fluent scientific English. Although scientific quality is
      the most important consideration, clear and concise writing often makes the
      difference between acceptance and rejection. As with any skill, efficient writing
      of high-quality manuscripts comes with experience and repetition. It is very
      uncommon for a manuscript to be accepted as submitted to a journal. Thoughtful
      and respectful responses to the journal reviewers' comments are critical. Success
      in scientific writing, as in surgery, is dependent on effort, repetition, and
      commitment. The transfer of knowledge through a well-written publication in a
      high-quality medical journal will have an impact not only in your own institution
      and country, but also throughout the world.

PMID- 29349529
TI  - Esophageal Cancer Surgery: Spontaneous Centralization in the US Contributed to
      Reduce Mortality Without Causing Health Disparities.
AB  - BACKGROUND: Improvement in mortality has been shown for esophagectomies performed
      at high-volume centers. OBJECTIVE: This study aimed to determine if
      centralization of esophageal cancer surgery occurred in the US, and to establish
      its impact on postoperative mortality. In addition, we aimed to analyze the
      relationship between regionalization of cancer care and health disparities.
      METHODS: A retrospective population-based analysis was performed using the
      National Inpatient Sample for the period 2000-2014. Adult patients (>= 18 years
      of age) diagnosed with esophageal cancer and who underwent esophagectomy were
      included. Yearly hospital volume was categorized as low (< 5 procedures),
      intermediate (5-20 procedures), and high (> 20 procedures). Multivariable
      analyses on the potential effect of hospital volume on patient outcomes were
      performed, and the yearly rate of esophagectomies was estimated using Poisson
      regression. RESULTS: A total of 5235 patients were included. Esophagectomy at low
      [odds ratio (OR) 2.17] and intermediate-volume (OR 1.62) hospitals, compared
      with high-volume hospitals, was associated with a significant increase in
      mortality. The percentage of esophagectomies performed at high-volume centers
      significantly increased during the study period (29.2-68.5%; p < 0.0001). The
      trend towards high-volume hospitals was different among the different US regions:
      South (7.7-54.3%), West (15.0-67.6%), Midwest (37.3-67.7%), and Northeast (55.8
      86.8%) [p < 0.0001]. Overall, the mortality rate of esophagectomy dropped from
      10.0 to 3.5% (p = 0.006), with non-White race, public insurance, and low
      household income patients also showing a significant reduction in mortality.
      CONCLUSIONS: A spontaneous centralization for esophageal cancer surgery occurred
      in the US. This process was associated with a decrease in the mortality rate,
      without contributing to health disparities.

PMID- 29349530
TI  - Photocatalytic activity of attapulgite-TiO2-Ag3PO4 ternary nanocomposite for
      degradation of Rhodamine B under simulated solar irradiation.
AB  - An excellent ternary composite photocatalyst consisting of silver orthophosphate
      (Ag3PO4), attapulgite (ATP), and TiO2 was synthesized, in which heterojunction
      was formed between dissimilar semiconductors to promote the separation of photo
      generated charges. The ATP/TiO2/Ag3PO4 composite was characterized by SEM, XRD,
      and UV-vis diffuse reflectance spectroscopy. The co-deposition of Ag3PO4 and TiO2
      nanoparticles onto the surface of ATP forms a lath-particle structure. Compared
      with composite photocatalysts consisting of two phases, ATP/TiO2/Ag3PO4 ternary
      composite exhibits greatly improved photocatalytic activity for degradation of
      rhodamine B under simulated solar irradiation. Such ternary composite not only
      improves the stability of Ag3PO4, but also lowers the cost by reducing
      application amount of Ag3PO4, which provides guidance for the design of Ag3PO4-
      and Ag-based composites for photocatalytic applications.

PMID- 29349531
TI  - An "All-In-One" Pharmacophoric Architecture for the Discovery of Potential Broad
      Spectrum Anti-Flavivirus Drugs.
AB  - A precipitous increase in the number of flaviviral infections has been noted over
      the last 5 years. Despite these outbreaks, treatment protocols for infected
      individuals remain ambiguous. Numerous studies have identified NITD008 as a
      potent flavivirus inhibitor; however, clinical testing was dismissed due to
      undesirable toxic effects. The binding landscape of NITD008 in complex with five
      detrimental flaviviruses at the RNA-dependent RNA polymerase active sites was
      explored. An "all-in-one" pharmacophore model was created for the design of small
      molecules that may inhibit a broad spectrum of flaviviruses. This pharmacophore
      model approach serves as a robust cornerstone, thus assisting medicinal experts
      in the composition of multifunctional inhibitors that will eliminate cross
      resistance and toxicity and enhance patient adherence.

PMID- 29349532
TI  - A Novel Approach in Treatment of Tuberculosis by Targeting Drugs to Infected
      Macrophages Using Biodegradable Nanoparticles.
AB  - Mycobacterium tuberculosis, the causative agent of tuberculosis is now causing
      death of more than 10 million people. Because of the development of drug
      resistant TB, drug delivery to the infected site through nanoparticle had been
      studied for long time. Nanoparticles indicate different sorts of association with
      the natural particles of the body. Nanoparticles can be used as controlled or
      specific drug delivery system. It can be through temporal controlled or can be
      distribution controlled. Glucose polymer-based nanoparticles might play an
      important role as drug delivery system in case of targeted drug delivery in the
      infected site of the body or in infected macrophages, as they are biodegradable
      so there should not be any side effects of these particles in the body and also
      they show very slow immune response. CD4, Beta 1, TGFb-1, IL-2, IL-13 SEC14L1,
      GUSB, BPI, and CCR7 are major biomarkers secreted after infection of this
      bacterium by the macrophages which can be used for targeted drug delivery in
      infected macrophages. As these markers can be used for delivery of drugs at
      destined position, they can be very beneficial in reducing toxicities of
      antituberculer drugs to the other uninfected sites and in operating only the
      infected macrophages.

PMID- 29349533
TI  - Hendra Virus Spillover is a Bimodal System Driven by Climatic Factors.
AB  - Understanding environmental factors driving spatiotemporal patterns of disease
      can improve risk mitigation strategies. Hendra virus (HeV), discovered in
      Australia in 1994, spills over from bats (Pteropus sp.) to horses and thence to
      humans. Below latitude - 22 degrees , almost all spillover events to horses occur
      during winter, and above this latitude spillover is aseasonal. We generated a
      statistical model of environmental drivers of HeV spillover per month. The model
      reproduced the spatiotemporal pattern of spillover risk between 1994 and 2015.
      The model was generated with an ensemble of methods for presence-absence data
      (boosted regression trees, random forests and logistic regression). Presences
      were the locations of horse cases, and absences per spatial unit (2.7 * 2.7 km
      pixels without spillover) were sampled with the horse census of Queensland and
      New South Wales. The most influential factors indicate that spillover is
      associated with both cold-dry and wet conditions. Bimodal responses to several
      variables suggest spillover involves two systems: one above and one below a
      latitudinal area close to - 22 degrees . Northern spillovers are associated with
      cold-dry and wet conditions, and southern with cold-dry conditions. Biologically,
      these patterns could be driven by immune or behavioural changes in response to
      food shortage in bats and horse husbandry. Future research should look for
      differences in these traits between seasons in the two latitudinal regions. Based
      on the predicted risk patterns by latitude, we recommend enhanced preventive
      management for horses from March to November below latitude 22 degrees  south.

PMID- 29349534
TI  - Psoriasis: from Pathogenesis to Targeted Therapies.
AB  - Over the last decade, the management of psoriasis has witnessed a paradigm shift.
      Thanks to the increasing knowledge about the pathogenesis of psoriasis, targeted
      treatments with monoclonal antibodies have been developed. These antibodies,
      which target the pathogenic TNF/IL-23/IL-17-pathway, were shown to be safe and
      efficacious in the management of most patients with moderate to severe chronic
      plaque psoriasis. Recently, molecular and genetic studies in pustular and
      erythrodermic psoriasis have identified additional inflammatory pathways,
      providing evidence that psoriasis is a heterogeneous disease and highlighting the
      requirement for personalized disease characterization for treatment optimization.
      In this article, we will review these advances and provide an update on the
      currently available treatment arsenal. We discuss the efficacy and safety profile
      of these individual therapeutic agents and describe their use in special
      indications. We will also describe the current understanding of psoriasis as a
      systemic disease associated with multiple comorbidities and illustrate its impact
      in the management of psoriatic patients. Finally, we discuss ongoing therapeutic
      developments as well as unmet needs and future perspectives in the field of
      psoriasis.

PMID- 29349535
TI  - Mycobacterium xenopi Genotype Associated with Clinical Phenotype in Lung Disease.
AB  - Mycobacterium xenopi is responsible for pulmonary disease (PD) in Europe and
      Canada. Despite its high prevalence and increasing clinical importance, little is
      known about the genetic diversity of M. xenopi. Through a prospective study for
      M. xenopi strain type and the relation to clinical phenotype, 39 patients with M.
      xenopi PD were analyzed. Our study demonstrated that sequence type (ST) 5 was
      dominant in Ontario among 15 distinct STs and caused PD in people even without
      underlying lung disease, whereas disease due to non-ST5 was found almost
      exclusively in patients with underlying lung disease.

PMID- 29349536
TI  - Oxygen Uptake Efficiency Slope and Prediction of Post-operative Morbidity and
      Mortality in Patients with Lung Cancer.
AB  - OBJECTIVE: Peak oxygen consumption is a very valuable cardiopulmonary functional
      parameter in pre-operative evaluation of patients with lung cancer. However, it
      has several critical limitations for operability decision due to failure in
      achieving maximal level of exercise test for cases. The aim of this study was to
      reveal the importance of more accurate cardiopulmonary parameters that can be
      calculated from data of submaximal level test, such as oxygen uptake efficiency
      slope (OUES) and to determine whether it could be used in the operability
      decision phase for borderline cases by means of morbidity and mortality.
      MATERIALS AND METHODS: One hundred and twenty-five patients who were scheduled to
      undergo lung surgery due to lung cancer were included in the study. Peak oxygen
      uptake (pVO2), heart rate at the anaerobic threshold, and oxygen consumption
      volume at anaerobic threshold values were obtained after performing the
      cardiopulmonary exercise test. The OUES value was calculated from the ratio of
      the peak VO2 value and logarithmic equivalent of the ventilatory volume (VE). The
      following equation was used for determining OUES: VO2/log10 VE. RESULTS: The peak
      VO2 mean value was 21.37 +/- 4.20 mL/min/kg in patients. However, OUES mean value
      was 12.44 +/- 2.11. When the metabolic parameters of the patients were compared,
      a significant correlation was determined between the peak VO2 value and peak VE,
      OUES, and survival (p < 0.01). CONCLUSION: This study demonstrated that OUES is
      significantly correlated with peak VO2 and it does not require the performance of
      maximal exercise and can be used together with peak VO2 in this patient
      population when there is difficulty in making decision for surgery in patients
      with lung cancer.

PMID- 29349537
TI  - Timing of Spirometry May Impact Hospital Length of Stay for Cystic Fibrosis
      Pulmonary Exacerbation.
AB  - PURPOSE: The optimal timing of spirometry during hospitalization for acute
      pulmonary exacerbation (PEx) in patients with cystic fibrosis (CF) is unclear. We
      retrospectively evaluated whether measuring spirometry earlier during
      hospitalization was associated with a shorter length of stay (LOS). METHODS: In
      this retrospective study, we analyzed data from the electronic medical record of
      CF patients 6 years of age and older admitted to a single center for acute PEx
      requiring IV antibiotic therapy between 2009 and 2016. After excluding patient
      encounters with missing data on covariates, random-effects linear regression was
      used to predict LOS as a function of days to first pulmonary function testing
      (PFT), which was spirometry for our study. RESULTS: One thousand thirty-five
      hospitalizations of 242 patients met inclusion criteria, with 801 including
      complete data on covariates. Mean LOS was 10 +/- 7 days, with mean time to first
      PFT of 4 +/- 3 days after admission. In multivariable analysis, each additional
      day to first PFT was associated with 0.97 days longer LOS (95% CI 0.29, 1.64; p =
      0.005). CONCLUSIONS: As CF researchers and clinicians work to improve management
      of PEx, the timing of spirometry during hospitalization remains an important
      question. Obtaining objective lung function data earlier during the course of
      therapy may provide information which can lead to reduced hospital LOS for PEx.

PMID- 29349538
TI  - Capturing pair-wise epistatic effects associated with three agronomic traits in
      barley.
AB  - Genetic association mapping has been widely applied to determine genetic markers
      favorably associated with a trait of interest and provide information for marker
      assisted selection. Many association mapping studies commonly focus on main
      effects due to intolerable computing intensity. This study aims to select several
      sets of DNA markers with potential epistasis to maximize genetic variations of
      some key agronomic traits in barley. By doing so, we integrated a MDR
      (multifactor dimensionality reduction) method with a forward variable selection
      approach. This integrated approach was used to determine single nucleotide
      polymorphism pairs with epistasis effects associated with three agronomic traits:
      heading date, plant height, and grain yield in barley from the barley Coordinated
      Agricultural Project. Our results showed that four, seven, and five SNP pairs
      accounted for 51.06, 45.66 and 40.42% for heading date, plant height, and grain
      yield, respectively with epistasis being considered, while corresponding
      contributions to these three traits were 45.32, 31.39, 31.31%, respectively
      without epistasis being included. The results suggested that epistasis model was
      more effective than non-epistasis model in this study and can be more preferred
      for other applications.

PMID- 29349539
TI  - Effect of the application of a bundle of three measures (intraperitoneal lavage
      with antibiotic solution, fascial closure with Triclosan-coated sutures and
      Mupirocin ointment application on the skin staples) on the surgical site
      infection after elective laparoscopic colorectal cancer surgery.
AB  - BACKGROUND: Surgical site infection (SSI) prevention bundles include the
      simultaneous use of different measures, which individually have demonstrated an
      effect on prevention of SSI. The implementation of bundles can yield superior
      results to the implementation of individual measures. The aim of this study was
      to address the effect of the application of a bundle including intraperitoneal
      lavage with antibiotic solution, fascial closure with Triclosan-coated sutures
      and Mupirocin ointment application on the skin staples, on the surgical site
      infection after elective laparoscopic colorectal cancer surgery. METHODS: A
      prospective, randomized study was performed, including patients with diagnosis of
      colorectal neoplasms and plans to undergo an elective laparoscopic surgery. The
      patients were randomized into two groups: those patients following standard
      bundles (Group 1) and those ones following the experimental bundle with three
      additional measures, added to the standard bundle. Incisional and organ space SSI
      were investigated. The study was assessor-blinded. RESULTS: A total of 198
      patients were included in the study, 99 in each group. The incisional SSI rate
      was 16% in Group 1 and 2% in Group 2 [p = 0.007; RR = 5.6; CI 95% (1.4-17.8)].
      The organ-space SSI rate was 4% in Group 1 and 0% in Group 2 [p = 0.039; RR =
      1.7; CI 95% (1.1-11.6)]. Median hospital stay was 5.5 days in Group 1 and 4 days
      in Group 2 (p = 0.028). CONCLUSIONS: The addition of intraperitoneal lavage with
      antibiotic solution, fascial closure with Triclosan-coated sutures and Mupirocin
      ointment application on the skin staples, to a standard bundle of SSI prevention,
      reduces the incisional and organ-space SSI and consequently the hospital stay,
      after elective laparoscopic colorectal cancer surgery (ClinicalTrials.gov
      Identifier: NCT03081962).

PMID- 29349540
TI  - Self-dilation for therapy-resistant benign esophageal strictures: towards a
      systematic approach.
AB  - BACKGROUND: Patients with therapy-resistant benign esophageal strictures (TRBES)
      suffer from chronic dysphagia and generally require repeated endoscopic
      dilations. For selected patients, esophageal self-dilation may improve patient's
      autonomy and reduce the number of endoscopic dilations. We evaluated the clinical
      course and outcomes of patients who started esophageal self-dilation at our
      institution. METHODS: This study was a retrospective case series of patients with
      TRBES who started esophageal self-dilation between 2012 and 2016 at the Academic
      Medical Center Amsterdam. To learn self-dilation using Savary-Gilliard bougie
      dilators, patients visited the outpatient clinic on a weekly basis where they
      were trained by a dedicated nurse. Endoscopic dilation was continued until
      patients were able to perform self-bougienage adequately. The primary outcome was
      the number of endoscopic dilation procedures before and after initiation of self
      dilation. Secondary outcomes were technical success, final bougie size, dysphagia
      scores, and adverse events. RESULTS: Seventeen patients started with esophageal
      self-dilation mainly because of therapy-resistant post-surgical (41%) and caustic
      (35%) strictures. The technical success rate of learning self-bougienage was 94%
      (16/17). The median number of endoscopic dilation procedures dropped from 17
      [interquartile range (IQR) 11-27] procedures during a median period of 9 (IQR 6
      36) months to 1.5 (IQR 0-3) procedures after the start of self-dilation (p <
      0.001). The median follow-up after initiation of self-dilation was 17.6 (IQR 11.5
      33.3) months. The final bougie size achieved with self-bougienage had a median
      diameter of 14 (IQR 13-15) mm. All patients could tolerate solid foods (Ogilvie
      dysphagia score <= 1), making the clinical success rate 94% (16/17). One patient
      (6%) developed a single episode of hematemesis related to self-bougienage.
      CONCLUSIONS: In this small case series, esophageal self-dilation was found to be
      successful 94% of patients when conducted under strict guidance. All patients
      performing self-bougienage achieved a stable situation where they could tolerate
      solid foods without the need for endoscopic dilation.

PMID- 29349541
TI  - Per oral endoscopic myotomy: early experience and safety of a multispecialty
      approach.
AB  - BACKGROUND: Per oral endoscopic myotomy (POEM) has gained increasing popularity
      for treating achalasia. A multidisciplinary approach may allow safe and early
      adoption of POEM into clinical practice. MATERIALS AND METHODS: We performed a
      retrospective review of our initial POEM cases. All procedures were performed by
      a team of interventional gastroenterologist and thoracic surgeon. We analyzed
      demographics, comorbidities, achalasia subtypes, length of hospital stay,
      duration of surgery, morbidity, mortality, length of myotomy, preoperative and
      postoperative Eckardt scores. RESULTS: Thirty-one consecutive patients underwent
      POEM during the 24-month period from January 2014 to December 2015. Eighteen
      patients (58%) had prior non-operative interventions. Average duration of follow
      up was 9.6 months. Seventeen patients (66.8%) had follow-up of 12 months and
      longer. Average preoperative Eckardt score was 6.3 (3-10), median 6. Average
      postoperative Eckardt score was 1.4 (0-8), median 1, in 1 month and an average
      2.2, median 1, in 1 year. Patients with type III achalasia were most refractory
      to treatment, while patients with type II had the best results. Average LOS was
      1.3 days (1-5), median 1 day. Average DOS was 106 min (60-148), median 106.
      Average LOM was 13 cm (10-15), with median of 13 cm. We had one 30-day mortality
      secondary to coronary artery disease. Four patients had prior Heller myotomies
      and underwent a posterior myotomy during POEM, with outcomes similar to patients
      with no prior myotomy. CONCLUSIONS: We demonstrated safety and efficiency of a
      multispecialty approach for achalasia with POEM with a low rate of complications.

PMID- 29349542
TI  - Laparoscopic pancreaticoduodenectomy with reconstruction of the mesentericoportal
      vein with the parietal peritoneum and the falciform ligament.
AB  - BACKGROUND: With the improvement of the surgical technique of Laparoscopic
      pancreaticoduodenectomy (LPD), indications will be extended to patients with
      vascular invasion. With LPD, vascular grafts for reconstruction are more
      frequently needed because adequate mobilization is not always done and vascular
      grafts can safely facilitate reconstruction. We describe our experience of
      reconstruction with the falciform ligament. METHODS: Venous reconstruction is
      performed after removal of the specimen. The falciform ligament is rapidly
      harvested within the same surgical field and for any size and used for lateral
      reconstruction of the mesentericoportal vein. Therapeutic anticoagulation is not
      needed and venous patency was assessed by postoperative CT scan. Since April 2011
      and among the 93 patients who underwent LPD, four patients had this procedure.
      RESULTS: The mean age was 73 years old (69-77) and 3 were women. Indications for
      resection were pancreatic adenocarcinoma (n = 3) and IPMN in severe dysplasia (n
      = 1) and the mean patch size of 13 mm (10-30). The mean operative time was 397
      min (330-480); vascular clamping lasted 54 min (45-60), and mean blood loss was
      437 ml (150-1000) and one was transfused. Resection was R0 in patients with
      adenocarcinoma (n = 3). The postoperative course was uneventful in 3 patients and
      one patient was re-operated for bile leak and partial venous thrombosis and redo
      venous reconstruction was done. Complete venous patency was demonstrated in
      patients (n = 2) who still alive 1 year after resection. CONCLUSION: Venous
      resection will be more frequently done with LPD and vascular grafts more
      frequently needed. Compared to other available vascular grafts (autogenous,
      synthetic, cadaveric and bovine pericardium, etc), the parietal peritoneum had
      the advantages of being rapidly available, easy to harvest by the laparoscopic
      approach, not expensive, no need for anticoagulation and at lower risk of
      infection.

PMID- 29349543
TI  - Saving robots improves laparoscopic performance: transfer of skills from a
      serious game to a virtual reality simulator.
AB  - BACKGROUND: Residents find it hard to commit to structural laparoscopic skills
      training. Serious gaming has been proposed as a solution on the premise that it
      is effective and more motivating than traditional simulation. We establish
      construct validity for the laparoscopic serious game Underground by comparing
      laparoscopic simulator performance for a control group and an Underground
      training group. METHODS: A four-session laparoscopic basic skills course is part
      of the medical master students surgical internship at the Radboud University
      Medical Centre. Four cohorts, representing 107 participants, were assigned to
      either the Underground group or the control group. The control group trained on
      the FLS video trainer and the LapSim virtual reality simulator for four sessions.
      The Underground group played Underground for three sessions followed by a
      transfer session on the FLS video trainer and the LapSim. To assess the effect of
      engaging in serious gameplay on performance on two validated laparoscopic
      simulators, initial performance on the FLS video trainer and the LapSim was
      compared between the control group (first session) and the Underground group
      (fourth session). RESULTS: We chose task duration as a proxy for laparoscopic
      performance. The Underground group outperformed the control group on all three
      LapSim tasks: Camera navigation F(1) = 12.71, p < .01; Instrument navigation F(1)
      = 8.04, p < .01; and Coordination F(1) = 6.36, p = .01. There was no significant
      effect of playing Underground for performance on the FLS video trainer Peg
      Transfer task, F(1) = 0.28, p = .60. CONCLUSIONS: We demonstrated skills transfer
      between a serious game and validated laparoscopic simulator technology. Serious
      gaming may become a valuable, cost-effective addition to the skillslab, if
      transfer to the operating room can be established. Additionally, we discuss
      sources of transferable skills to help explain our and previous findings.

PMID- 29349544
TI  - Interpretation of motion analysis of laparoscopic instruments based on principal
      component analysis in box trainer settings.
AB  - BACKGROUND: Motion analysis parameters (MAPs) have been extensively validated for
      assessment of minimally invasive surgical skills. However, there are
      discrepancies on how specific MAPs, tasks, and skills match with each other,
      reflecting that motion analysis cannot be generalized independently of the
      learning outcomes of a task. Additionally, there is a lack of knowledge on the
      meaning of motion analysis in terms of surgical skills, making difficult the
      provision of meaningful, didactic feedback. In this study, new higher
      significance MAPs (HSMAPs) are proposed, validated, and discussed for the
      assessment of technical skills in box trainers, based on principal component
      analysis (PCA). METHODS: Motion analysis data were collected from 25 volunteers
      performing three box trainer tasks (peg grasping/PG, pattern cutting/PC, knot
      suturing/KS) using the EVA tracking system. PCA was applied on 10 MAPs for each
      task and hand. Principal components were trimmed to those accounting for an
      explained variance > 80% to define the HSMAPs. Individual contributions of MAPs
      to HSMAPs were obtained by loading analysis and varimax rotation. Construct
      validity of the new HSMAPs was carried out at two levels of experience based on
      number of surgeries. RESULTS: Three new HSMAPs per hand were defined for PG and
      PC tasks, and two per hand for KS task. PG presented validity for HSMAPs related
      to insecurity and economy of space. PC showed validity for HSMAPs related to
      cutting efficacy, peripheral unawareness, and confidence. Finally, KS presented
      validity for HSMAPs related with economy of space and knotting security.
      CONCLUSIONS: PCA-defined HSMAPs can be used for technical skills' assessment.
      Construct validation and expert knowledge can be combined to infer how
      competences are acquired in box trainer tasks. These findings can be exploited to
      provide residents with meaningful feedback on performance. Future works will
      compare the new HSMAPs with valid scoring systems such as GOALS.

PMID- 29349545
TI  - Risk of discontinuation of clopidogrel after 1 month following bare-metal stents:
      a propensity-score adjusted comparison with continued administration of
      clopidogrel after drug-eluting stents.
AB  - In patients at high risk for bleeding undergoing percutaneous coronary
      intervention (PCI) the use of bare-metal-stent (BMS) is considered an option that
      allows discontinuation of clopidogrel after 4 weeks. We sought to investigate the
      risk of early discontinuation of clopidogrel in patients with BMS as compared
      with a 6-month course of clopidogrel after DES in patients with or without high
      on-treatment platelet reactivity (HTPR). In 765 consecutive patients undergoing
      PCI after loading with clopidogrel 600 mg, HTPR was tested by optical
      aggregometry and defined as residual platelet reactivity > 14%. On top of aspirin
      100 mg, patients received clopidogrel 75 mg for 4 weeks after BMS or 6 months
      after DES. The primary endpoint was all-cause mortality or myocardial infarction
      (MI) during 1 year. The 1-year incidence of death or MI was 3.5% with BMS (n =
      484), 0.9% with DES and no HTPR (n = 211), and 7.1% with DES and HTPR (n = 70; p
      = 0.03). Landmark analyses for the first 6 months demonstrated that the risk of
      patients receiving BMS was similar as in patients receiving a DES with HTPR
      during this period (2.3 vs. 2.9%) but lowest in patients receiving a DES without
      HTPR (0.5%). The incidence of bleeding was similar in all three groups. These
      findings did not change after propensity score adjustment for stent type. After
      discontinuation of clopidogrel at 1 month, patients treated with BMS are at
      higher risk for death or MI than patients treated with a DES and sufficiently
      responding to clopidogrel planned for 6 months.ClinicalTrials.gov number
      NCT00457236.

PMID- 29349546
TI  - Understanding Who Benefits from Parenting Interventions for Children's Conduct
      Problems: an Integrative Data Analysis.
AB  - Parenting interventions are an effective strategy to reduce children's conduct
      problems. For some families, that is, not all families benefit equally.
      Individual trials tend to be underpowered and often lack variability to
      differentiate between families how benefit less or more. Integrating individual
      family level data across trials, we aimed to provide more conclusive results
      about often presumed key family (parental education and ethnic background) and
      child characteristics (problem severity, ADHD symptoms and emotional problems) as
      putative moderators of parenting intervention effects. We included data from 786
      families (452 intervention; 334 control) from all four trials on the Incredible
      Years parenting intervention in The Netherlands (three randomized; one matched
      control). Children ranged between 2 and 10 years (M = 5.79; SD = 1.66). Of the
      families, 31% had a lower educational level and 29% had an ethnic minority
      background. Using multilevel regression, we tested whether each of the putative
      moderators affected intervention effects. Incredible Years reduced children's
      conduct problems (d = - .34). There were no differential effects by families'
      educational or ethnic background, or by children's level of ADHD symptoms.
      Children with more severe conduct problems and those with more emotional problems
      benefited more. Post hoc sensitivity analyses showed that for the two trials with
      longer-term data, moderation effects disappeared at 4 or 12 months follow-up.
      Often assumed moderators have some, but limited abilities to explain who benefits
      from parenting interventions. This suggests the need for studying theoretically
      more precise moderators in prevention research, other than relatively static
      family characteristics alone.

PMID- 29349547
TI  - Heterologous expression of two Aspergillus niger feruloyl esterases in
      Trichoderma reesei for the production of ferulic acid from wheat bran.
AB  - Feruloyl esterase (FAE)-encoding genes AnfaeA and AnfaeB were isolated from
      Aspergillus niger 0913. For overexpression of the two genes in Trichoderma
      reesei, constitutive and inductive expression plasmids were constructed based on
      parental plasmid pAg1-H3. The constructed plasmids contained AnfaeA or AnfaeB
      gene under the control of glyceraldehyde-3-phosphate dehydrogenase A gene (gpdA)
      promoter (from A. nidulans) or cellobiohydrolases I (cbh I) gene promoter (from
      T. reesei), and cbh I terminator from T. reesei. The target plasmids were
      transferred into T. reesei D-86271 (Rut-C30) by Agrobacterium tumefaciens
      mediated transformation (ATMT), respectively. A high level of feruloyl esterase
      was produced by the recombinant fungal strains under solid-state fermentation,
      and the cbh I promoter was more efficient than the gpdA promoter in the
      expression of AnfaeA. The optimum temperatures and pH values were 50  degrees C
      and 5.0 for AnFAEA, and 35  degrees C and 6.0 for AnFAEB. The maximum production
      levels were 20.69 U/gsd for AnFAEA and 15.08 U/gsd for AnFAEB. The recombinant
      fungal enzyme systems could release 62.9% (for AnFAEA) and 52.2% (for AnFAEB) of
      total ferulic acids from de-starched wheat bran, which was higher than the 46.3%
      releasing efficiency of A. niger 0913. The supplement of xylanase from T.
      longibrachiatum in the enzymatic hydrolysis led to a small increment of the
      ferulic acids release.

PMID- 29349548
TI  - An effective surfactant-assisted hydrothermal pretreatment strategy for
      bioethanol production from chili post-harvest residue by separate hydrolysis and
      fermentation.
AB  - Surfactants play major role in the delignification of lignocellulosic biomass.
      Surfactant-assisted hydrothermal pretreatment was evaluated for chili post
      harvest residue. Maximum reducing sugar yield of 0.445 g per g of dry biomass
      (g/g) was obtained when surfactant PEG 6000 was used. Compositional analysis
      revealed an efficient removal of lignin and hemicelluloses from the pretreated
      biomass. Fermentation inhibitors such as furfural, 5-hydroxymethylfurfural and
      organic acids were absent in the hydrolyzate. After pretreatment, the biomass can
      be directly hydrolyzed without any neutralization, washing and drying, and the
      hydrolyzate is devoid of major fermentation inhibitors. Fermentation with
      Saccharomyces cerevisiae yielded 1.84% of ethanol with a fermentation efficiency
      of 63.88%.

PMID- 29349549
TI  - Biodegradation of Mordant orange-1 using newly isolated strain Trichoderma
      harzianum RY44 and its metabolite appraisal.
AB  - Herein, we systematically reported the capability of T. harzianum RY44 for
      decolorization of Mordant orange-1. The fungi strains were isolated from the
      Universiti Teknologi Malaysia tropical rain forest. For initial screening, the
      decolorization was conducted using 50 strains of the fungi for 20 days incubation
      time and the best performance was selected. Then, the decolorization capability
      and fungal biomass were evaluated using different dye concentrations, namely, 0,
      50, 75 and 100 ppm. Effects of the carbon sources (fructose, glucose, and
      galactose), nitrogen sources (ammonium nitrate, ammonium sulfate and yeast
      extract), surfactant (tween 80), aromatic compounds (benzoic acid, catechol and
      salicylic acid), and pH on the decolorization efficiency were examined. This
      study has found that the employed carbon sources, nitrogen sources, and aromatic
      compounds strongly enhance the decolorization efficiency. In addition, increasing
      the surfactant volume and pH generally decreased the decolorization efficiencies
      from 19.5 to 9.0% and 81.7 to 60.5%, respectively. In the mechanism philosophy,
      the present work has found that Mordant orange-1 were initially degraded by T.
      harzianum RY44 to benzoic acid and finally transformed into salicylic acid.

PMID- 29349550
TI  - Recombinase polymerase amplification combined with lateral flow dipstick for
      equipment-free detection of Salmonella in shellfish.
AB  - Salmonella is a major pathogen that causes acute foodborne outbreaks worldwide.
      Seafood, particularly shellfish, is a proven source of Salmonella spp. infection
      because many people prefer to eat it raw or lightly cooked. However, traditional
      identification methods are too time-consuming and complex to detect contamination
      of bacteria in the food chain in a timely manner, and few studies have aimed to
      identify Salmonella in shellfish early in the supply chain. We herein developed a
      method for rapid detection of Salmonella in shellfish based on the method of
      recombinase polymerase amplification (RPA) combined with lateral flow dipstick
      (LFD), which targets the invasion gene A (invA). The RPA-LFD was able to function
      at 30-45  degrees C, and at the temperature of 40  degrees C, it only took 8 min
      of amplification to reach the test threshold of amplicons. The established method
      had both a good specificity and a sensitivity of 100 fg DNA per reaction (20 uL).
      Regarding practical performance, RPA-LFD performed better than real-time PCR.
      Another advantage of RPA-LFD is that it was capable of being performed without
      expensive equipments. Thus, RPA-LFD has potential for further development as a
      detection kit for Salmonella in shellfish and other foods under field conditions.

PMID- 29349551
TI  - Medical Marijuana: Current Concepts, Pharmacological Actions of Cannabinoid
      Receptor Mediated Activation, and Societal Implications.
AB  - PURPOSE OF REVIEW: The purpose of the following review is to summarize the
      history and current policies related to marijuana use and prevalence, basic and
      clinical science pharmacological literature regarding efficacy, subpopulations of
      concern, and varying policies regarding its use at present. RECENT FINDINGS: With
      the increasingly widespread utilization of marijuana, there is also a growing
      complexity of public health policy, regulation, and necessity to further assess
      the medical indications and adverse long-term effects of marijuana use. Health
      care providers as well as the general public must be prepared to become familiar
      and up-to-date with medical literature, legislation, and educational material
      regarding medical marijuana.

PMID- 29349552
TI  - European Network of Trainees in Obstetrics and Gynaecology-ENTOG Exchange 2017:
      an experience report from Slovenia outlining the different trainee situations
      around Europe.
AB  - PURPOSE: The European Network of Trainees in Obstetrics and Gynaecology (ENTOG)
      is a non-profit, independent organisation that represents young trainees in
      obstetrics and gynaecology around Europe. At present, ENTOG has 32 member
      countries. The organisation was founded in 1997 and shall assure the exchange of
      experiences between young physicians all over Europe. The aim is to improve the
      quality of traineeship in all participating countries and consequently enhance
      the standards for women's healthcare. METHODS: This article reports about the
      experiences of trainees during the ENTOG Exchange 2017 in Slovenia and gives an
      overview of the trainee situations in different ENTOG member countries. RESULTS:
      The ENTOG exchange in Slovenia was a unique opportunity to get insights to the
      Slovenian medical system. Reflecting about their training situations, the
      participants found considerable differences in the training of young
      gynaecologists throughout Europe. CONCLUSIONS: Working on the ENTOG goal of
      raising the quality of training is still highly relevant. The ENTOG exchange is
      an excellent way to build a network among trainees and stimulate their commitment
      to improve women's healthcare in their home countries and beyond.

PMID- 29349553
TI  - Differential JNK, p38 and ERK response to renal injury in a rat model of acute
      pancreatitis in pregnancy.
AB  - OBJECTIVE: The objective of this study was to determine the mechanism of acute
      renal injury (ARI) in acute necrotizing pancreatitis in late pregnancy (ANPIP).
      METHODS: Pregnant Sprague-Dawley rats in the third trimester were used for this
      study, and an ANPIP model was induced by injecting 5% sodium taurocholate into
      the biliary pancreatic duct. The rats were randomly divided into three groups:
      the normal, sham-operated (SO) and acute necrotizing pancreatitis (ANP) groups.
      Rats were killed at 3, 6, 12 h after the operation, and blood, pancreatic and
      renal tissue samples were harvested. Differences were detected in the physiology,
      pathology and cellular and molecular responses among the different groups.
      RESULT: Serum amylase, lipase, urea and Cr levels were increased in rats with
      ANPIP. Additionally, expression of phosphorylation p38 and JNK as well as TNF
      alpha and NF-kappaB were increased in the renal tissues of rats with ANPIP. The
      expression of phosphorylation ERK was decreased in the renal tissues of rats with
      ANPIP. CONCLUSIONS: Mitogen-activated protein kinases may play an important role
      in renal injury in rat models of ANPIP.

PMID- 29349554
TI  - Comment on "Contemporary epidemiology and novel predictors of uterine rupture: a
      nationwide population-based study".

PMID- 29349555
TI  - Letter to the Editor: Comment on "Contemporary epidemiology and novel predictors
      of uterine rupture: a nationwide population-based study".

PMID- 29349556
TI  - Neuropathology correlates of cognitive assessments.
AB  - BACKGROUND: Alzheimer's disease and other dementias are the fourth largest
      contributors to neurological disability and the second largest contributor to
      deaths from neurological disease. Described in the 1980s as 'the silent epidemic'
      these disorders principally, though not exclusively, affect persons 80 years or
      older, and in developed countries, this 'old old' population continues to grow.
      Definitive diagnosis of the underlying cause of the neurodegenerative disease
      relies on neuropathological evaluation.' AIMS: Herein, we review the sampling
      methods, analysis and interpretation of both pathological and immunocytochemical
      techniques in the diagnostic assessment of neurodegenerative disease. FINDINGS:
      Neurodegenerative disorders are characterised by accumulation of pathologically
      altered protein in the human brain, and in some cases, in the peripheral tissues.
      Whilst it is suggested that a comprehensive review of the patient's clinical
      history, cognition and behaviour, together with a full clinical examination and
      radiological analysis, should lead to a high degree of confidence in the clinical
      diagnosis, the view persists that underlying pathology can only be predicted on
      clinical grounds especially in Alzheimer's disease, vascular brain injury and
      diffuse Lewy body disease with only limited accuracy. CONCLUSIONS:
      Neuropathological assessment of well characterised clinical cases provides
      accurate data on the prevalence of neurodegenerative diseases. This will aid
      future biomarker, neuroimaging studies and clinical trials focussed on population
      based cohorts.

PMID- 29349557
TI  - A rare ocular complication of neisseria gonorrhoeae.
AB  - BACKGROUND: Spontaneous formation of subconjunctival filtering blebs is rare and
      has been observed after penetrating ocular surgery, in association with
      connective tissue diseases and inflammatory conditions. METHOD: We describe here
      a case of a spontaneous formation of subconjunctival filtering bleb as sequelae
      of gonococcal conjunctivitis in an adult patient. RESULTS: Spontaneous filtering
      bleb is a rare complication of gonococcal conjunctivitis. In this case, the
      patient presented with a recent history of gonococcal conjunctivitis treated with
      moxifloxacin eye drops and intravenous cephalothin for a week. On the first exam,
      there was superior corneal thinning with surrounding conjunctival hyperemia and
      edema in the right eye, but after the patient lost the follow-up for 2 weeks, the
      corneal thinning had become a pseudopterygium. After another week, we observed a
      focal elevation on the superior conjunctiva that had the appearance of a bleb,
      although the anterior chamber remained deep. The filtering bleb was confirmed by
      ultrasound biomicroscopy examination (UBM). CONCLUSION: This case is relevant to
      the clinical practice because filtering blebs should be considered as a
      complication of gonococcal conjunctivitis because they pose a threat to the eye
      when substantial leakage occurs.

PMID- 29349558
TI  - SGLT2 Inhibitors and Mechanisms of Hypertension.
AB  - PURPOSE OF REVIEW: We sought to review currently available data on the safety and
      efficacy of sodium-glucose cotransporter 2 (SGLT2) inhibitors in type 2 diabetes
      mellitus patients with hypertension. RECENT FINDINGS: Inhibition of SGLT2 in the
      renal proximal tubule results in increased urinary glucose excretion and modest
      improvements of hemoglobin A1C. Treatment with any of the three currently FDA
      approved SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin) results
      in sustained systolic and diastolic blood pressure reduction, in part via minimal
      natriuresis and possible reductions in sympathetic tone. Recent randomized
      clinical trials in high cardiovascular risk patients with type 2 diabetes suggest
      that the unique effects of SGLT2 inhibitors on blood pressure and body weight may
      translate into reduced cardiovascular events and slowed kidney disease
      progression. However, concerns about volume depletion and acute kidney injury
      have been raised. SGLT2 inhibitors are viable second-line glucose-lowering agents
      for people with type 2 diabetes with high cardiovascular risk.

PMID- 29349560
TI  - Effect of fibrillatory wave amplitude on coronary blood flow as assessed by
      thrombolysis in myocardial infarction frame count in patients with atrial
      fibrillation.
AB  - Atrial fibrillation (AF) is the most common arrhythmia, characterized by a lack
      of atrial contraction and an irregular ventricular rhythm. We assessed the effect
      of fibrillatory wave amplitude on coronary blood flow in patients with AF using
      the thrombolysis in myocardial infarction (TIMI) frame count. Sixty-one patients
      with AF persisting for longer than 30 days were included. For controls, 61 age-
      and sex-matched patients with sinus rhythm were selected. Coarse AF was defined
      as any fibrillatory wave >= 1 mm and fine AF as any fibrillatory wave < 1 mm.
      Mean TIMI frame count was significantly higher in patients with AF than in those
      with sinus rhythm (18 +/- 4 vs 30 +/- 11, p < 0.001). Multivariate analysis
      showed that AF was the only determinant of mean TIMI frame count (beta = 0.48, p
      < 0.001). Among patients with AF, 32 had coarse AF and 29 had fine AF. Left
      atrial volume index (54 +/- 14 vs 64 +/- 21 ml/m2, p = 0.03) was significantly
      larger, and mean TIMI frame count (26 +/- 7 vs 35 +/- 12, p < 0.001) was
      significantly higher in patients with fine AF than in those with coarse AF.
      Multivariate analysis showed that hypertension (beta = - 0.29, p = 0.01) and a
      fine fibrillatory wave (beta = 0.33, p = 0.007) were determinants of mean TIMI
      frame count. Our data suggest that coronary blood flow is reduced in patients
      with AF compared with those with sinus rhythm, and that a fine fibrillatory wave
      is a major determinant of reduced coronary blood flow in patients with AF.

PMID- 29349561
TI  - Sphenopalatine ganglion stimulation for cluster headache, results from a large,
      open-label European registry.
AB  - BACKGROUND: Cluster headache (CH) is a disabling primary headache disorder
      characterized by severe periorbital pain. A subset of patients does not respond
      to established pharmacological therapy. This study examines outcomes of a cohort
      of mainly chronic CH patients treated with sphenopalatine ganglion (SPG)
      stimulation. METHODS: Patients were followed in an open-label prospective study
      for 12 months. Ninety-seven CH patients (88 chronic, 9 episodic) underwent trans
      oral insertion of a microstimulator targeting the SPG. Patients recorded
      stimulation effect prospectively for individual attacks. Frequency, use of
      preventive and acute medications, headache impact (HIT-6) and quality of life
      measures (SF-36v2) were monitored at clinic visits. Per protocol, frequency
      responders experienced >= 50% reduction in attack frequency and acute responders
      treated >= 50% of attacks. HIT-6 responders experienced an improvement >= 2.3
      units and SF-36 responders >= 4 units vs. baseline. RESULTS: Eighty-five patients
      (78 chronic, 7 episodic) remained implanted and were evaluated for effectiveness
      at 12 months. In total, 68% of all patients were responders, 55% of chronic
      patients were frequency responders and 32% of all patients were acute responders.
      67% of patients using acute treatments were able to reduce the use of these by
      52% and 74% of chronic patients were able to stop, reduce or remain off all
      preventive medications. 59% of all patients were HIT-6 responders, 67% were SF-36
      responders. CONCLUSIONS: This open-label registry corroborates that SPG
      stimulation is an effective therapy for CH patients providing therapeutic
      benefits and improvements in use of medication as well as headache impact and
      quality of life.

PMID- 29349559
TI  - A mutant HCN4 channel in a family with bradycardia, left bundle branch block, and
      left ventricular noncompaction.
AB  - We found that a female infant presenting with left bundle branch block and left
      ventricular noncompaction carries uninvestigated gene mutations HCN4(G811E),
      SCN5A(L1988R), DMD(S2384Y), and EMD(R203H). Here, we explored the possible
      pathogenicity of HCN4(G811E), which results in a G811E substitution in
      hyperpolarization-activated cyclic nucleotide-gated channel 4, the main subunit
      of the cardiac pacemaker channel. Voltage-clamp measurements in a heterologous
      expression system of HEK293T cells showed that HCN4(G811E) slightly reduced whole
      cell HCN4 channel conductance, whereas it did not affect the gating kinetics,
      unitary conductance, or cAMP-dependent modulation of voltage-dependence.
      Immunocytochemistry and immunoblot analysis showed that the G811E mutation did
      not impair the membrane trafficking of the channel subunit in the heterologous
      expression system. These findings indicate that HCN4(G811E) may not be a
      monogenic factor to cause the cardiac disorders.

PMID- 29349562
TI  - The influence of elevated hormone levels on physiologic accumulation of 68Ga
      DOTATOC.
AB  - OBJECTIVE: PET/CT imaging with 68Ga-1,4,7,10-tetraazacyclododecane-N,N',N",N'''
      tetraacetic acid-D-Phe1-Tyr3-octreotide (DOTATOC) is useful in patients with
      neuroendocrine tumors (NETs). Functioning NETs by definition secrete abnormal
      levels of hormones, causing clinical symptoms. It is known that physiologic
      accumulation can be seen in some organs, but it remains unknown whether elevated
      hormone levels can affect the physiologic accumulation pattern of 68Ga-DOTATOC.
      We aimed to investigate the influence of higher hormone levels on physiologic
      accumulation of 68Ga-DOTATOC. METHODS: A total of 167 patients with known or
      suspected NET lesions were enrolled in this study. The numbers of patients with
      elevations of ACTH, gastrin, insulin, and no elevation were 10, 25, 7, and 125,
      respectively. We compared the maximum standardized uptake value (SUVmax) in
      various organs of each group. RESULTS: In the group with elevated ACTH levels,
      SUVmax in the pituitary gland, the uncinate process of the pancreas and adrenal
      glands was lower than those in the group with no elevation (5.7 +/- 1.9 vs. 8.4
      +/- 3.1, P = 0.015; 4.7 +/- 3.5 vs. 6.4 +/- 2.8, P = 0.037; 10.8 +/- 4.8 vs. 13.9
      +/- 4.7, P = 0.020, respectively). There were no differences in physiologic
      uptake of 68Ga-DOTATOC in the thyroid gland, the pancreatic body, the liver, the
      spleen, the bowel, or the kidney. CONCLUSIONS: In NET patients with elevated ACTH
      levels, physiologic uptake of 68Ga-DOTATOC in the pituitary gland, the uncinate
      process of the pancreas and adrenal glands was significantly decreased. Other
      organs were unaffected.

PMID- 29349564
TI  - Retraction Note to: Factors associated with post-stroke depression and fatigue:
      lesion location and coping styles.
AB  - The Editors-in-Chief are retracting the original article because it shows
      significant overlap with an article previously published by the authors [1]. All
      authors agree to this retraction.

PMID- 29349565
TI  - Description of Alteromonas abrolhosensis sp. nov., isolated from sea water of
      Abrolhos Bank, Brazil.
AB  - Two Gram-negative, motile, aerobic bacteria isolated from waters of the Abrolhos
      Bank were classified through a whole genome-based taxonomy. Strains PEL67ET and
      PEL68C shared 99% 16S rRNA and dnaK sequence identity with Alteromonas marina SW
      47T and Alteromonas macleodii ATCC 27126T. In silico DNA-DNA Hybridization, i.e.
      genome-to-genome distance (GGD), average amino acid identity (AAI) and average
      nucleotide identity (ANI) showed that PEL67ET and PEL68C had identity values
      between 33-36, 86-88 and 83-84%, and 85-86 and 83%, respectively, towards their
      close neighbors A. macleodii ATCC 27126T and A. marina SW-47T. The DNA G + C
      contents of PEL67ET and PEL68C were 44.5%. The phenotypic features that
      differentiate PEL67ET and PEL68C strains from their close neighbors were
      assimilation of galactose and activity of phosphatase, and lack of mannitol,
      maltose, acetate, xylose and glycerol assimilation and lack of lipase, alpha and
      beta-glucosidase activity. The new species Alteromonas abrolhosensis is proposed.
      The type strain is PEL67ET (= CBAS 610T = CAIM 1925T).

PMID- 29349566
TI  - Performance Improvement in Head and Neck Cancer.
AB  - Performance improvement requires establishing a platform to set benchmarks and
      monitor the quality of care provided through quality indicators and metrics. This
      has long been recognized as critical to overall quality improvement and more
      recently, has become federally mandated. Here, we review recent studies
      evaluating performance in head and neck cancer care, from those spanning all
      phases of head and neck cancer care to others focused on head and neck surgical
      performance, including both national and departmental/institutional efforts.

PMID- 29349567
TI  - HBeAg induces the expression of macrophage miR-155 to accelerate liver injury via
      promoting production of inflammatory cytokines.
AB  - Activation of Kupffer cells (KCs) induced that inflammatory cytokine production
      plays a central role in the pathogenesis of HBV infection. The previous studies
      from our and other laboratory demonstrated miRNAs can regulate TLR-inducing
      inflammatory responses to macrophage. However, the involvement of miRNAs in HBV
      associated antigen-induced macrophage activation is still not thoroughly
      understood. Here, we evaluated the effects and mechanisms of miR-155 in HBV
      associated antigen-induced macrophage activation. First, co-culture assay of
      HepG2 or HepG2.2.15 cells and RAW264.7 macrophages showed that HepG2.2.15 cells
      could significantly promote macrophages to produce inflammatory cytokines.
      Furthermore, we, respectively, stimulated RAW264.7 macrophages, mouse primary
      peritoneal macrophages, or healthy human peripheral blood monocytes with HBV
      associated antigens, including HBcAg, HBeAg, and HBsAg, and found that only HBeAg
      could steadily enhance the production of inflammatory cytokines in these cells.
      Subsequently, miRNAs sequencing presented the up- or down-regulated expression of
      multiple miRNAs in HBeAg-stimulated RAW264.7 cells. In addition, we verified the
      expression of miR-155 and its precursors BIC gene with q-PCR in the system of co
      culture or HBeAg-stimulated macrophages. Meanwhile, the increased miR-155
      expression was positively correlation with serum ALT, AST, and HBeAg levels in
      AHB patients. Although MAPK, PI3K, and NF-kappaB signal pathways were all
      activated during HBeAg treatment, only PI3K and NF-kappaB pathways were involved
      in miR-155 expression induced by HBeAg stimulation. Consistently, miR-155 over
      expression inhibited production of inflammatory cytokines, which could be
      reversed by knocking down miR-155. Moreover, we demonstrated that miR-155
      regulated HBeAg-induced cytokine production by targeting BCL-6, SHIP-1, and SOCS
      1. In conclusion, our data revealed that HBeAg augments the expression of miR-155
      in macrophages via PI3K and NF-kappaB signal pathway and the increased miR-155
      promotes HBeAg-induced inflammatory cytokine production by inhibiting the
      expression of BCL-6, SHIP-1, and SOCS-1.

PMID- 29349568
TI  - Class III bacteriocin Helveticin-M causes sublethal damage on target cells
      through impairment of cell wall and membrane.
AB  - Helveticin-M, a novel Class III bacteriocin produced by Lactobacillus crispatus
      exhibited an antimicrobial activity against Staphylococcus aureus, S.
      saprophyticus, and Enterobacter cloacae. To understand how Helveticin-M injured
      target cells, Helveticin-M was cloned and heterologously expressed in Escherichia
      coli. Subsequently, the cell wall organization and cell membrane integrity of
      target cells were determined. The mechanism of cellular damage differed according
      to bacterial species. Based on morphology analysis, Helveticin-M disrupted the
      cell wall of Gram-positive bacteria and disorganized the outer membrane of Gram
      negative bacteria, therefore, altering surface structure. Helveticin-M also
      disrupted the inner membrane, as confirmed by leakage of intracellular ATP from
      cells and depolarization of membrane potential of target bacteria. Based on cell
      population analysis, Helveticin-M treatment caused the increase of cell membrane
      permeability, but the cytosolic enzymes were not influenced, indicating that it
      was the sublethal injury. Therefore, the mode of Helveticin-M action is
      bacteriostatic rather than bactericidal.

PMID- 29349569
TI  - xylA and xylB overexpression as a successful strategy for improving xylose
      utilization and poly-3-hydroxybutyrate production in Burkholderia sacchari.
AB  - Despite the versatility and many advantages of polyhydroxyalkanoates as petroleum
      based plastic substitutes, their higher production cost compared to petroleum
      based polymers has historically limited their large-scale production. One
      appealing approach to reducing production costs is to employ less expensive,
      renewable feedstocks. Xylose, for example is an abundant and inexpensive carbon
      source derived from hemicellulosic residues abundant in agro-industrial waste
      (sugarcane bagasse hemicellulosic hydrolysates). In this work, the production of
      poly-3-hydroxybutyrate P(3HB) from xylose was studied to develop technologies for
      conversion of agro-industrial waste into high-value chemicals and biopolymers.
      Specifically, this work elucidates the organization of the xylose assimilation
      operon of Burkholderia sacchari, a non-model bacterium with high capacity for
      P(3HB) accumulation. Overexpression of endogenous xylose isomerase and
      xylulokinase genes was successfully assessed, improving both specific growth rate
      and P(3HB) production. Compared to control strain (harboring pBBR1MCS-2), xylose
      utilization in the engineered strain was substantially improved with 25% increase
      in specific growth rate, 34% increase in P(3HB) production, and the highest
      P(3HB) yield from xylose reported to date for B. sacchari (YP3HB/Xil = 0.35 g/g).
      This study highlights that xylA and xylB overexpression is an effective strategy
      to improve xylose utilization and P(3HB) production in B. sacchari.

PMID- 29349570
TI  - Assessment of ten density functionals through the use of local hyper-softness to
      get insights about the catalytic activity : Iron-based organometallic compounds
      for ethylene polymerization as testing molecules.
AB  - Ten functionals were used to assess their capability to compute a local
      reactivity descriptor coming from the Conceptual Density Functional Theory on a
      group of iron-based organometallic compounds that have been synthesized by
      Zohuri, G.H. et al. in 2010; these compounds bear the following substituent
      groups: H-, O2N- and CH3O- at the para position of the pyridine ring and their
      catalytic activities were experimentally measured by these authors. The present
      work involved a theoretical analysis applied on the aforementioned iron-based
      compounds thus leading to suggest a new 2,6-bis(imino)pyridine catalyst based on
      iron(II) bearing a fluorine atom whose possible catalytic activity is suggested
      to be near the catalytic activity of the complex bearing a hydrogen atom as a
      substituent group by means of the so called local hyper-softness (LHS) thus
      opening a chance to estimate a possible value of catalytic activity for a new
      catalyst that has not been synthesized yet without simulating the entire process
      of ethylene polymerization. Since Conceptual DFT is not a predictive theory, but
      rather interpretative, an analysis of the used reactivity descriptor and its
      dependence upon the level of theory was carried in the present work, thus
      revealing that care should be taken when DFT calculations are used for these
      purposes.

PMID- 29349571
TI  - Fluoroscopy-free ultrasonography-guided percutaneous nephrolithotomy in pediatric
      patients: a single-center experience.
AB  - OBJECTIVES: To present the safety and efficacy of fluoroscopy-free ultrasound
      guided PCNL for the treatment of renal calculi in pediatric patients of all ages.
      METHODS: 30 children with mean age of 5 years (6 months-12 years) underwent
      totally ultrasound-guided PCNL from March 2013 to August 2016. The pyelocalyceal
      system was punctured in prone position using only ultrasonography guidance, and
      the tract was dilated using a single shot dilation technique. No fluoroscopy was
      used during any of the stages of renal access. The procedure was performed using
      adult-sized instruments. RESULTS: The mean stone size was 27.1 +/- 8.7 mm. Mean
      access time was 4.3 +/- 2 min. Mean nephroscopic time was 34.6 +/- 15.2 min. Mean
      hospital stay of patients was 3 days (range 2-5). 21 patients were stone-free
      after the procedure (70% success rate). Only four patients out of 30 experienced
      postoperative complications. CONCLUSIONS: The results of this study showed that
      fluoroscopic-free ultrasound-guided PCNL in pediatric patients of all ages is
      safe, highly efficient, and minimizes potential radiation exposure risks
      associated with the procedure.

PMID- 29349572
TI  - A prospective study evaluating indirect MRI-signs for the prediction of
      extraprostatic disease in patients with prostate cancer: tumor volume, tumor
      contact length and tumor apparent diffusion coefficient.
AB  - OBJECTIVE: The aim of this study was to evaluate three indirect MRI signs for
      predicting extraprostatic disease in patients referred to radical prostatectomy:
      index tumor volume (MTV), apparent diffusion coefficient (ADC) and tumor contact
      length (TCL). MATERIALS AND METHODS: This prospective study included 183 patients
      with biopsy proven prostate cancer. In all patients the MTV (ml), ADC (* 10-5
      mm2/s) and TCL (mm) of the index tumor were registered at the preoperative MRI.
      Whole-mounted microscopical examination classified each patient as having either
      localized- or extraprostatic disease. The Youden index was used to identify the
      optimal cut-off values for predicting extraprostatic disease. Univariate
      regression analyses were conducted to estimate the odds ratio (OR) with 95%
      confidence intervals (CI). Results were stratified upon zonal location of the
      index tumor. RESULTS: Extraprostatic disease was identified in 103 (56%)
      patients. The risk of extraprostatic disease was nine times higher in peripheral
      zone tumors with ADC <= 89 (OR 9.1, 95% CI 4.2-19.6), five times higher in MTV >=
      0.9 ml (OR 5.5, 95% CI 2.6-11.4) and five times higher in case of TCL >= 14 mm
      (OR 4.9, 95% CI 2.3-10.2). None of the indirect MRI signs could predict
      extraprostatic disease for transition zone tumors. CONCLUSION: The MTV, ADC and
      TCL are all significant predictors of extraprostatic disease for peripheral zone
      tumors, while none of the indirect signs were useful for transition zone tumors.

PMID- 29349573
TI  - Mesencephalic Astrocyte-Derived Neurotrophic Factor (MANF) Elevates Stimulus
      Evoked Release of Dopamine in Freely-Moving Rats.
AB  - Neurotrophic factors (NTFs) hold potential as disease-modifying therapies for
      neurodegenerative disorders like Parkinson's disease. Glial cell line-derived
      neurotrophic factor (GDNF), cerebral dopamine neurotrophic factor (CDNF), and
      mesencephalic astrocyte-derived neurotrophic factor (MANF) have shown
      neuroprotective and restorative effects on nigral dopaminergic neurons in various
      animal models of Parkinson's disease. To date, however, their effects on brain
      neurochemistry have not been compared using in vivo microdialysis. We measured
      extracellular concentration of dopamine and activity of dopamine neurochemistry
      regulating enzymes in the nigrostriatal system of rat brain. NTFs were
      unilaterally injected into the striatum of intact Wistar rats. Brain
      microdialysis experiments were performed 1 and 3 weeks later in freely-moving
      animals. One week after the treatment, we observed enhanced stimulus-evoked
      release of dopamine in the striatum of MANF-treated rats, but not in rats treated
      with GDNF or CDNF. MANF also increased dopamine turnover. Although GDNF did not
      affect the extracellular level of dopamine, we found significantly elevated
      tyrosine hydroxylase (TH) and catechol-O-methyltransferase (COMT) activity and
      decreased monoamine oxidase A (MAO-A) activity in striatal tissue samples 1 week
      after GDNF injection. The results show that GDNF, CDNF, and MANF have divergent
      effects on dopaminergic neurotransmission, as well as on dopamine synthetizing
      and metabolizing enzymes. Although the cellular mechanisms remain to be
      clarified, knowing the biological effects of exogenously administrated NTFs in
      intact brain is an important step towards developing novel neurotrophic
      treatments for degenerative brain diseases.

PMID- 29349574
TI  - Pacific Ciguatoxin Induces Excitotoxicity and Neurodegeneration in the Motor
      Cortex Via Caspase 3 Activation: Implication for Irreversible Motor Deficit.
AB  - Consumption of fish containing ciguatera toxins or ciguatoxins (CTXs) causes
      ciguatera fish poisoning (CFP). In some patients, CFP recurrence occurs even
      years after exposure related to CTXs accumulation. Pacific CTX-1 (P-CTX-1) is one
      of the most potent natural substances known that causes predominantly
      neurological symptoms in patients; however, the underlying pathogenies of CFP
      remain unknown. Using clinically relevant neurobehavioral tests and
      electromyography (EMG) to assess effects of P-CTX-1 during the 4 months after
      exposure, recurrent motor strength deficit occurred in mice exposed to P-CTX-1.
      We detected irreversible motor strength deficits accompanied by reduced EMG
      activity, demyelination, and slowing of motor nerve conduction, whereas control
      unexposed mice fully recovered in 1 month after peripheral nerve injury. Finally,
      to uncover the mechanism underlying CFP, we detected reduction of spontaneous
      firing rate of motor cortical neurons even 6 months after exposure and increased
      number of glial fibrillary acidic protein (GFAP)-immunoreactive astrocytes.
      Increased numbers of motor cortical neuron apoptosis were detected by dUTP
      digoxigenin nick end labeling assay along with activation of caspase 3. Taken
      together, our study demonstrates that persistence of P-CTX-1 in the nervous
      system induces irreversible motor deficit that correlates well with
      excitotoxicity and neurodegeneration detected in the motor cortical neurons.

PMID- 29349575
TI  - Parkin in Parkinson's Disease and Cancer: a Double-Edged Sword.
AB  - Parkin for more than a decade has been portrayed as a neuroprotector gene is now
      increasingly emerging as a multifaceted gene that can exert entirely opposite
      effects i.e., both cell proliferation and apoptosis. Parkinson's disease, a
      neurological disease, progresses due to excess in cell death, while, in case of
      cancer, cell death normally fails to occur. Parkin, an E3 ubiquitin ligase, was
      first identified as a gene implicated in autosomal recessive juvenile
      Parkinsonism, but several evidences indicate that Parkin is a tumor suppressor
      gene, involved in a variety of cancers. It is hard to imagine that two entirely
      different classes of disease, like cancer and Parkinson's disease, can converge
      at a critical point attributable to a single gene, Parkin. This mysterious and
      hidden connection may prove a boon in disguise and has raised hopes that studying
      the biology of one disease may help to identify novel targets of therapy for the
      other. In this Parkinson's disease-cancer story, if the detail of Parkin pathway
      is unraveled and gaps in the storyline are properly filled up, we may end getting
      an entirely new therapeutic option. This review mainly highlights the recent
      literature which suggests how Parkin gene regulates the various hallmarks of both
      the Parkinson's disease and cancer.

PMID- 29349576
TI  - Prep1 Deficiency Affects Olfactory Perception and Feeding Behavior by Impairing
      BDNF-TrkB Mediated Neurotrophic Signaling.
AB  - Prep1 is a homeodomain transcription factor which has an important role in
      hindbrain development. Prep1 expression is also kept in adult mouse brain and in
      particular within the olfactory bulbs. Moreover, many Prep1 neurons co-localize
      with Calbindin-positive periglomerular interneurons in olfactory glomerular
      layer. However, Prep1 function in this brain region is still unknown. In this
      study, we show that Prep1 hypomorphic heterozygous (Prep1i/+) mice express low
      levels of protein and feature a 30% reduction of olfactory bulb area, compared to
      WT mice. In addition, Prep1i/+ mice olfactory bulb histological analysis
      indicated a 20% lower cytochrome C oxidase activity within the glomerular layer,
      accompanied by a reduced number of periglomerular interneurons, compared to the
      WT littermates. Consistently, olfactory perception test highlighted that Prep1
      hypomorphic heterozygous mice display a scant ability to distinguish odors, which
      significantly impacts on feeding behavior, as Prep1i/+ mice revealed a reduced
      preference for high-fat food. Analysis of BDNF signaling, which represents the
      main molecular mediator of olfactory plasticity, showed that Prep1i/+ mouse
      olfactory bulbs feature a 30% reduction of TrkB receptor levels and a decreased
      activation of ERK1/2. Similarly, overexpression of Prep1 in mouse neuronal cells
      (N2A) caused an increase of TrkB expression levels, BDNF-induced ERK
      phosphorylation, and cell viability, compared to control cells. We conclude that
      Prep1 deficiency alters olfactory morpho-functional integrity and olfaction
      mediated eating behavior by affecting BDNF-TrkB signaling. Prep1 could,
      therefore, play a crucial role in behavioral dysfunctions associated to impaired
      responsiveness to BDNF.

PMID- 29349578
TI  - In Situ Tissue Labeling of Cerebral Amyloid Using HIV-Related Tat Peptide.
AB  - Delivering peptide-based drugs to the brain is a major challenge because of the
      existence of the blood-brain barrier (BBB). To overcome this problem, cell
      penetrating peptides derived from proteins that are able to cross biological
      membranes have been used as cell-permeable and brain-penetrant compounds. An
      example is the transactivator of transcription protein transduction domain (Tat)
      of the human immunodeficiency virus. The basic domain of Tat is formed of
      arginine and lysine amino acid residues. Tat has been used as brain-penetrant
      carrier also in therapies for Alzheimer disease (AD), the most common form of
      dementia characterized by extracellular cerebral deposits of amyloid made up of
      Abeta peptide. The aim of our study was to assess whether Tat bind to amyloid
      deposits of AD and other amyloidoses. An in situ labeling using biotinylated Tat
      48-57 peptide was employed in the brain tissue with amyloid deposits made up of
      Abeta (patients with AD and transgenic AD mice), of prion protein (patients with
      Gerstmann-Straussler-Scheinker disease), and other amyloidosis, processed by
      different fixations and pretreatments of histological sections. Our results
      showed that Tat peptide binds amyloid deposits made up of Abeta, PrP, and
      immunoglobulin lambda chains in the brain and other tissues processed by
      alcoholic fixatives but not in formalin-fixed tissue. The fact that biotinylated
      Tat peptide stains amyloid of different biochemical composition and the specific
      charge characteristics of the molecules suggests that Tat may bind to heparan
      sulfate glicosaminoglicans, that are present in amyloid deposits. Inhibition of
      the binding by Tat pre-incubation with protamine reinforces this hypothesis.
      Binding of Tat to amyloid deposits should be kept in mind in interpreting the
      results of studies employing this molecule as brain-penetrating compound for the
      treatment of cerebral amyloidoses. Our results also suggest that Tat may be
      helpful for the analysis of the mechanisms of amyloidogenesis, and in particular,
      the interactions between specific amyloid peptides and glicosaminoglicans.

PMID- 29349577
TI  - Combination Therapy with Sulfasalazine and Valproic Acid Promotes Human
      Glioblastoma Cell Death Through Imbalance of the Intracellular Oxidative
      Response.
AB  - Glioblastoma (GBM) is the most common and aggressive malignant primary brain
      tumor and still lacks effective therapeutic strategies. It has already been shown
      that old drugs like sulfasalazine (SAS) and valproic acid (VPA) present
      antitumoral activities in glioma cell lines. SAS has also been associated with a
      decrease of intracellular glutathione (GSH) levels through a potent inhibition of
      xc- glutamate/cystine exchanger leading to an antioxidant deprotection. In the
      same way, VPA was recently identified as a histone deacetylase (HDAT) inhibitor
      capable of activating tumor suppression genes. As both drugs are widely used in
      clinical practice and their profile of adverse effects is well known, the aim of
      our study was to investigate the effects of the combined treatment with SAS and
      VPA in GBM cell lines. We observed that both drugs were able to reduce cell
      viability in a dose-dependent manner and the combined treatment potentiated these
      effects. Combined treatment also increased cell death and inhibited proliferation
      of GBM cells, while having no effect on human and rat cultured astrocytes. Also,
      we observed high protein expression of the catalytic subunit of xc- in all the
      examined GBM cell lines, and treatment with SAS blocked its activity and
      decreased intracellular GSH levels. Noteworthy, SAS but not VPA was also able to
      reduce the [14C]-ascorbate uptake. Together, these data indicate that SAS and VPA
      exhibit a substantial effect on GBM cell's death related to an intracellular
      oxidative response imbalance, making this combination of drugs a promising
      therapeutic strategy.

PMID- 29349579
TI  - Malaria infectivity of xanthurenic acid-deficient anopheline mosquitoes produced
      by TALEN-mediated targeted mutagenesis.
AB  - Anopheline mosquitoes are major vectors of malaria parasites. When the
      gametocytes of the malaria parasite are transferred from a vertebrate to
      mosquitoes, they differentiate into gametes, and are fertilized in the midguts of
      mosquitoes. Xanthurenic acid (XA), a waste product of the ommochrome synthesis
      pathway, has been shown to induce exflagellation during microgametogenesis in
      vitro; however, it currently remains unclear whether endogenous XA affects the
      infectivity of anopheline mosquitoes to malaria parasites in vivo due to the lack
      of appropriate experimental systems such as a XA-deficient line. In the present
      study, we produced a XA-deficient line in Anopheles stephensi using transcription
      activator-like effector nuclease (TALEN)-mediated gene targeting (knockout) of
      the kynurenine 3-monooxygenase (kmo) gene, which encodes an enzyme that
      participates in the ommochrome synthesis pathway. The knockout of kmo resulted in
      the absence of XA, and oocyst formation was inhibited in the midguts of these XA
      deficient mosquitoes, which, in turn, reduced sporozoite numbers in their
      salivary glands. These results suggest that endogenous XA stimulates
      exflagellation, and enhances the infectivity of anopheline mosquitoes to malaria
      parasites in vivo. The XA-deficient line of the anopheline mosquito provides a
      useful system for analyzing and understanding the associated factors of malaria
      gametogenesis in the mosquito midgut.

PMID- 29349580
TI  - Perianesthetic Management of Laparoscopic Kidney Surgery.
AB  - PURPOSE OF REVIEW: Laparoscopic kidney surgery is commonly used for living donor,
      partial, and total tumor nephrectomy. The successful emergence of laparoscopic
      technique was justified by the many benefits offered such as reduced blood loss,
      tissue trauma, pain, and hospital stay. However, this comes at the expense of
      physiologic changes and complications secondary to pneumoperitoneum, surgical
      technique, and patient positioning with significant challenges in anesthetic
      management. RECENT FINDINGS: A variety of laparoscopic approaches
      (transperitoneal, retroperitoneal, hand-assisted, robotic) are used with some
      having advantages over others. The kidneys are particularly sensitive to
      hemodynamic changes and pneumoperitoneum. Controversies in perioperative fluid
      administration exist. New modalities for postoperative pain control have been
      suggested. Laparoscopic kidney surgery is associated with multiple physiologic
      changes and adverse events but offers advantages of reduced postoperative pain,
      faster recovery, and shorter hospital stay. Understanding these physiologic
      changes and related anesthetic considerations is key for safe patient outcome.

PMID- 29349581
TI  - Quantitative assessment of thyroid gland elasticity with shear-wave elastography
      in pediatric patients with Hashimoto's thyroiditis.
AB  - OBJECTIVE: Hashimoto's thyroiditis is the most common autoimmune thyroid disorder
      in the pediatric age range. Measurement of thyroid gland size is an essential
      component in evaluation and follow-up of thyroid pathologies. Along with size,
      tissue elasticity is becoming a more commonly used parameter in evaluation of
      parenchyma in inflammatory diseases. The aim of the current study was to assess
      thyroid parenchyma elasticity by shear-wave elastography in pediatric patients
      with Hashimoto's thyroiditis; and compare the elasticity values to a normal
      control group. MATERIALS AND METHODS: In this study; thyroid glands of 59
      patients with a diagnosis of Hashimoto's thyroiditis based on ultrasonographic
      and biochemical features, and 26 healthy volunteers without autoimmune thyroid
      disease and thyroid function disorders, were evaluated with shear-wave
      elastography. Patients with Hashimoto thyroiditis were further subdivided into
      three categories based on gray-scale ultrasonography findings as focal
      thyroiditis (grade 1), diffuse thyroiditis (grade 2), and fibrotic thyroid gland
      (grade 3). RESULTS: Patients with Hashimoto's thyroiditis (n = 59) had
      significantly higher elasticity values (14. 9 kPa; IQR 12.9-17.8 kPa) than
      control subjects (10.6 kPa; IQR 9.0-11.3 kPa) (p < 0.001). Of the 59 patients
      with Hashimoto's thyroiditis, 23 patients had focal thyroiditis involving less
      than 50% of the gland categorized as grade 1, 24 patients had diffuse involvement
      of the thyroid gland categorized as grade 2, and 12 patients had marked
      hyperechoic septations and pseudonodular appearance categorized as grade 3 on
      gray-scale ultrasound. Based on elastography, grade 3 patients had significantly
      higher elasticity values (19.7 kPa; IQR 17.8-21.5 kPa) than patients with grade 2
      (15.5 kPa; IQR 14.5-17.8 kPa) and grade 1 thyroiditis (12.8 kPa; IQR 11.9-13.1
      kPa) (p < 0.05). Patients with grade 2 thyroiditis had significantly higher
      elasticity values than those with grade 1 thyroiditis (p < 0.05). CONCLUSION:
      Gray-scale ultrasound findings of heterogeneous echotexture and hypoechoic
      echogenicity reflect a longer duration of inflammation and may not be found in
      the initial stages of thyroiditis. Our results indicate that shear-wave
      elastography could be used to evaluate the degree of fibrosis in Hashimoto's
      thyroiditis.

PMID- 29349582
TI  - Can we evaluate the levator ani after Kegel exercise in women with pelvic organ
      prolapse by transperineal elastography? A preliminary study.
AB  - OBJECTIVES: The aim of this study was to evaluate the stiffness variation of the
      levator ani in patients with stage I/II pelvic organ prolapse (POP) before and
      after Kegel exercises by transperineal elastography. METHODS: A total of 20
      patients who were diagnosed with staged I/II POP underwent conventional
      transperineal ultrasound and elastography. For each patient, the levator ani was
      located and evaluated in the state of Valsalva. After Kegel exercises for 12
      weeks, transperineal ultrasound and elastography were repeated. The elasticity
      images were assessed using a four-point scale scoring system. RESULTS: Of the 20
      cases, four had an elastography score of 1, 14 had a score of 2, two had a score
      of 3, and no cases had a score of 4 in the levator ani before Kegel exercises.
      After Kegel exercises, one had an elastography score of 1, two had a score of 2,
      15 had a score of 3, and two cases had a score of 4. The mean elastography score
      was statistically significantly higher for the levator ani after Kegel exercises
      (2.90 +/- 0.48) than for the baseline score (1.90 +/- 0.29) (p = 0.025).
      CONCLUSIONS: Transperineal elastography was an effective and useful tool in the
      evaluation of the levator ani in patients with POP-Q stage I/II before and after
      Kegel exercises.

PMID- 29349583
TI  - Enhanced production of phenolic acids in cell suspension culture of Salvia
      leriifolia Benth. using growth regulators and sucrose.
AB  - Salvia leriifolia Benth. (Lamiaceae) is an endangered medicinal plant with
      hypoglycemic, anti-inflammatory and analgesic properties. Many of the beneficial
      effects of Salvia spp. are attributed to the phenolic compounds. In the present
      study, an efficient procedure has been developed for establishment of cell
      suspension culture of S. leriifolia as a strategy to obtain an in vitro phenolic
      acids producing cell line for the first time. The effect of growth regulators and
      various concentrations of sucrose have been analyzed, to optimize biomass growth
      and phenolic acids production. The callus used for this purpose was obtained from
      leaves of 15-day-old in vitro seedlings, on Murashige and Skoog (MS) basal medium
      supplemented with different hormone balances including benzylaminopurine (BAP)
      and indole butyric acid (IBA); 2,4-dichlorophenoxyacetic acid (2,4-D) and kinetin
      (KIN); naphthaleneacetic acid (NAA) and BAP. Modified MS medium supplemented with
      5 mg/L BAP and 5 mg/L NAA was the optimal condition for callus formation with the
      highest induction rate (100%), the best callus growth and the highest phenolic
      acids content. No callus induction was observed in combinations of IBA and BAP.
      Cell suspension cultures were established by transferring 0.5 g of callus to 30
      mL liquid MS medium supplemented with 5 mg/L BAP and 5 mg/L NAA. Dynamics of
      phenolic acids production has been investigated during the growth cycle of the
      suspension cultures. The maximum content of caffeic acid and salvianolic acid B
      were observed on the 15th day of the cultivation cycle while the highest amount
      of rosmarinic acid was observed on the first day. In response to various sucrose
      concentrations, cell cultures with 40 g/L sucrose not only produced the highest
      dry biomass but also the highest induction of caffeic acid and salvianolic acid
      B. The highest amount of rosmarinic acid was observed in media containing 50 g/L
      sucrose. These prepared cell suspension cultures provided a useful system for
      further enhanced production of phenolic acids at a large scale.

PMID- 29349584
TI  - [Percutaneous endoscopic gastrostomy in geriatrics : Indications, technique and
      complications].
AB  - The technique of percutaneous endoscopic gastrostomy (PEG) was introduced in 1979
      as a semi-invasive approach for children with the need for a gastric fistula in
      order to avoid an operative intervention. The suture pull-through method was
      rapidly established and is now omnipresent. Because scientific evidence is
      broadly missing, there is some uncertainty about the indications in geriatric
      medicine. Guidelines do not recommend the insertion of a PEG in patients with
      severe dementia and malnutrition. Tube feeding is mainly recommended as a
      temporary method for patients who cannot take oral nutrition for more than 3 days
      or for whom the energy intake for more than 10 days presumably covers less than
      50% of their needs, assuming that the overall prognosis is reasonable. Insertion
      of a PEG is only recommended if artificial nutrition is expected to be necessary
      for more than 3-4 weeks or if a nasogastric tube is not tolerated.

PMID- 29349585
TI  - Molecularly Imprinted Core-Shell CdSe@SiO2/CDs as a Ratiometric Fluorescent Probe
      for 4-Nitrophenol Sensing.
AB  - 4-Nitrophenol (4-NP) is a priority pollutant in water and is both carcinogenic
      and genotoxic to humans and wildlife even at very low concentrations. Thus, we
      herein fabricated a novel molecularly imprinted core-shell nanohybrid as a
      ratiometric fluorescent sensor for the highly sensitive and selective detection
      of 4-NP. This sensor was functioned by the transfer of fluorescence resonance
      energy between photoluminescent carbon dots (CDs) and 4-NP. This sensor was
      synthesized by linking organosilane-functionalized CDs to silica-coated CdSe
      quantum dots (CdSe@SiO2) via Si-O bonds. The nanohybrids were further modified by
      anchoring a molecularly imprinted polymer (MIP) layer on the ratiometric
      fluorescent sensor through a facile sol-gel polymerization method. The
      morphology, chemical structure, and optical properties of the resulting
      molecularly imprinted dual-emission fluorescent probe were characterized by
      transmission electron microscopy and spectroscopic analysis. The probe was then
      applied in the detection of 4-NP and exhibited good linearity between 0.051 and
      13.7 MUg/mL, in addition to a low detection limit of 0.026 MUg/mL. Furthermore,
      the simplicity, reliability, high selectivity, and high sensitivity of the
      developed sensor demonstrate that the combination of MIPs and ratiometric
      fluorescence allows the preparation of excellent fluorescent sensors for the
      detection of trace or ultra-trace analytes.

PMID- 29349586
TI  - Cancer incidence among children and young adults who have undergone x-ray guided
      cardiac catheterization procedures.
AB  - Children and young adults with heart disease appear to be at increased risk of
      developing cancer, although the reasons for this are unclear. A cohort of 11,270
      individuals, who underwent cardiac catheterizations while aged <= 22 years in the
      UK, was established from hospital records. Radiation doses from cardiac
      catheterizations and CT scans were estimated. The cohort was matched with the NHS
      Central Register and NHS Transplant Registry to determine cancer incidence and
      transplantation status. Standardized incidence ratios (SIR) with associated
      confidence intervals (CI) were calculated. The excess relative risk (ERR) of
      lymphohaematopoietic  neoplasia was also calculated using Poisson regression. The
      SIR was raised for all malignancies (2.32, 95% CI 1.65, 3.17), lymphoma (8.34,
      95% CI 5.22, 12.61) and leukaemia (2.11, 95% CI 0.82, 4.42). After censoring
      transplant recipients, post-transplant, the SIR was reduced to 0.90 (95% CI 0.49,
      1.49) for all malignancies. All lymphomas developed post-transplant. The SIR for
      all malignancies developing 5 years from the first cardiac catheterization (2
      years for leukaemia/lymphoma) remained raised (3.01, 95% CI 2.09, 4.19) but was
      again reduced after censoring transplant recipients (0.98, 95% CI 0.48, 1.77).
      The ERR per mGy bone marrow dose for lymphohaematopoietic neoplasia was reduced
      from 0.541 (95% CI 0.104, 1.807) to 0.018 (95% CI - 0.002, 0.096) where
      transplantation status was accounted for as a time-dependent background risk
      factor. In conclusion, transplantation appears to be a large contributor to
      elevated cancer rates in this patient group. This is likely to be mainly due to
      associated immunosuppression, however, radiation exposure may also be a
      contributing factor.

PMID- 29349587
TI  - The Danish Medical Birth Register.
AB  - The Danish Medical Birth Register was established in 1973. It is a key component
      of the Danish health information system. The register enables monitoring of the
      health of pregnant women and their offspring, it provides data for quality
      assessment of the perinatal care in Denmark, and it is used extensively for
      research. The register underwent major changes in construction and content in
      1997, and new variables have been added during the last 20 years. The aim was to
      provide an updated description of the register focusing on structure, content,
      and coverage since 1997. The register includes data on all births in Denmark and
      comprises primarily of data from the Danish National Patient Registry
      supplemented with forms on home deliveries and stillbirths. It contains
      information on maternal age provided by the Civil Registration System.
      Information on pre-pregnancy body mass index and smoking in first trimester is
      collected in early pregnancy (first antenatal visit). The individual-level data
      can be linked to other Danish health registers such as the National Patient
      Registry and the Danish National Prescription Registry. The register informs
      several other registers/databases such as the Danish Twin Registry and the Danish
      Fetal Medicine Database. Aggregated data can be publicly accessed on the Danish
      Health Data Authority web page ( www.esundhed.dk/sundhedsregistre/MFR ).
      Researchers can obtain access to individual-level pseudo-anonymised data via
      servers at Statistics Denmark and the Danish Health Data Authority.

PMID- 29349588
TI  - Amphiregulin enhances cardiac fibrosis and aggravates cardiac dysfunction in mice
      with experimental myocardial infarction partly through activating EGFR-dependent
      pathway.
AB  - Cardiac fibrosis (CF), a main process of ventricular remodeling after myocardial
      infarction (MI), plays a crucial role in the pathogenesis of heart failure (HF)
      post-MI. It is known that amphiregulin (AR) is involved in fibrosis of several
      organs. However, the expression of AR and its role post-MI are yet to be
      determined. This study aimed to investigate the impact of AR on CF post-MI and
      related mechanisms. Significantly upregulated AR expression was evidenced in the
      infarct border zone of MI mice in vivo and the AR secretion was enhanced in
      macrophages, but not in cardiac fibroblasts. In vitro, treatment with AR
      increased cardiac fibroblast migration, proliferation and collagen synthesis, and
      upregulated the expression of epidermal growth factor receptor (EGFR) and the
      downstream genes such as Akt, ERK1/2 and Samd2/3 on cardiac fibroblasts. All
      these effects could be abrogated by pretreatment with a specific EGFR inhibitor.
      To verify the functions of AR in MI hearts, lentivirus-AR-shRNA and negative
      control vectors were delivered into the infarct border zone. After 28 days, knock
      down of AR increased the survival rate and improved cardiac function, while
      decreasing the extent of myocardial fibrosis of MI mice. Moreover, EGFR and the
      downstream genes were significantly downregulated in lentivirus-AR-shRNA treated
      MI mice. Our results thus indicate that AR plays an important role in promoting
      CF after MI partly though activating the EGFR pathway. Targeting AR might be a
      novel therapeutic option for attenuating CF and improve cardiac function after
      MI.

PMID- 29349589
TI  - Associations Between Father Temperament, Character, Rearing, Psychopathology and
      Child Temperament in Children Aged 3-6 Years.
AB  - Temperament refers to the totality of individual characteristics present from
      birth that determine a child's unique style of behavior. Maternal personality and
      attitudes, one of the factors affecting temperament traits in children, is a
      frequently investigated subject. However, paternal variables have remained
      insufficiently studied. The purpose of this study is to investigate the
      associations between the fathers' temperament, character, attitudes,
      psychopathology and temperament of the 3-6 years-old children. The parents of 36
      60 months-old children in the preschool settings in Samsun were included in the
      study (n:200). Their mothers completed "Maternal Sociodemographic Form" prepared
      by the researcher, and the temperament of children "Children Behaviour
      Questionnare" were scored by the mothers. Their fathers completed "Paternal
      Sociodemographic Form", and to assess father psychopathology "Brief Symptom
      Inventory", to determine father temperament and character "Temperament and
      Character Inventory" and to determine attitudes "Parenting Attitudes Scale" were
      scored by the fathers. In this study, we found several significant associations
      between children's temperament and fathers temperament and character, attitudes
      styles and psychopathology. The scores of paternal harm avoidance increase and
      self directedness decrease were found to be significantly positivily correlated
      with negative temperamental charecteristics of the children. The democratic
      attitudes of fathers were significantly correlated with positive temperamental
      scores of the children. All domains of paternal psychopathology were found to be
      in significant association with negative temperamental characteristics of the
      children. Our findings showed the complex interplay between determinants of
      parenting. Specifically, this study is one of the first to investigate paternal
      personality, psychopathology and attitudes, alone and in interaction with
      preschool child temperament.

PMID- 29349590
TI  - Law as Clinical Evidence: A New ConstitutiveModel of Medical Education and
      Decision-Making.
AB  - Over several decades, ethics and law have been applied to medical education and
      practice in a way that reflects the continuation during the twentieth century of
      the strong distinction between facts and values. We explain the development of
      applied ethics and applied medical law and report selected results that reflect
      this applied model from an empirical project examining doctors' decisions on
      withdrawing/withholding treatment from patients who lack decision-making
      capacity. The model is critiqued, and an alternative "constitutive" model is
      supported on the basis that medicine, medical law, and medical ethics exemplify
      the inevitable entanglement of facts and values. The model requires that ethics
      and law be taught across the medical education curriculum and integrated with the
      basic and clinical sciences and that they be perceived as an integral component
      of medical evidence and practice. Law, in particular, would rank as equal in
      normative authority to the relevant clinical scientific "facts" of the case, with
      graduating doctors having as strong a basic command of each category as the
      other. The normalization of legal knowledge as part of the clinician's evidence
      base to be utilized in practice may provide adequate consolation for clinicians
      who may initially resent further perceived incursions on their traditional
      independence and discretion.

PMID- 29349591
TI  - Radical resection of a giant retroperitoneal calcifying fibrous tumor combined
      with right hepatectomy and reconstruction of the inferior vena cava and bilateral
      renal veins.
AB  - BACKGROUND: We report a case of a giant retroperitoneal calcifying fibrous tumor
      (CFT) treated by radical tumor resection combined with right hepatectomy and
      reconstruction of the inferior vena cava (IVC) and bilateral renal veins. Only
      three case reports of CFT arising in the retroperitoneum have been reported until
      today. CASE PRESENTATION: In a 19-year-old female patient, computed tomography
      (CT) images showed a well-demarcated expansile lesion around the IVC accompanied
      by focal calcification, whereas the IVC that was circumferentially surrounded by
      the lesion was dilated due to the desmoplastic reaction. On magnetic resonance
      imaging (MRI), the lesion demonstrated heterogeneous hypointensity on T2-weighted
      images. Delayed enhancement was observed on dynamic contrast-enhanced CT and MRI.
      18F-Fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT images showed
      increased FDG uptake [maximum standardized uptake values (SUVmax), early image
      7.28; delayed image 7.40]. On operative examination, because the tumor adhered to
      the liver parenchyma, the right Glisson capsule, and the origin of bilateral
      renal veins, radical tumor resection combined with right hepatectomy and
      reconstruction of the IVC and bilateral renal veins was performed. CONCLUSIONS:
      Radical tumor resection was successfully and appropriately performed for a young
      patient with a giant retroperitoneal CFT with a view to achieving complete venous
      reconstruction and safe surgical margins for a potentially malignant tumor.

PMID- 29349592
TI  - Overview of Current and Future Adjuvant Therapy for High-Risk Localized Renal
      Cell Carcinoma.
AB  - OPINION STATEMENT: High-risk localized renal cell carcinoma represents a
      therapeutic challenge with high recurrence rates and poor survival with
      nephrectomy alone. Multiple agents targeting angiogenic and immunologic pathways
      have demonstrated remarkable efficacy in the metastatic setting but have failed
      to replicate similar successes in localized disease. Study results with adjuvant
      anti-angiogenic therapies may have been compromised by the high incidence of
      treatment discontinuations or dosage reductions secondary to intolerable side
      effects. Improving patient selection could play a major role in improving
      outcomes. Multiple models exist to predict survival but require improved accuracy
      in identifying recurrence to justify exposing patients to therapies that could
      significantly impair quality of life. Further understanding of pathological and
      molecular mechanisms of recurrence is required. Novel tools like gene recurrence
      scores are emerging to improve prognostication for patient selection.
      Immunotherapeutic approaches using check point inhibition have the potential to
      achieve sustained remissions with a significantly improved toxicity profile.
      Amplifying the immune response with a combination of neoadjuvant and adjuvant
      therapy to exploit the larger antigenic burden prior to nephrectomy has the
      biologic potential for making significant improvements in efficacy.

PMID- 29349593
TI  - BodiMojo: Efficacy of a Mobile-Based Intervention in Improving Body Image and
      Self-Compassion among Adolescents.
AB  - Mobile interventions promoting positive body image are lacking. This study
      presents a randomized controlled evaluation of BodiMojo, a mobile application
      (app) intervention grounded in self-compassion to promote positive body image. A
      sample of 274 adolescents, mean (SD) age = 18.36 (1.34) years, 74% female, were
      allocated to a control group or used BodiMojo for 6 weeks. Appearance esteem,
      body image flexibility, appearance comparison, mood, and self-compassion were
      assessed at baseline, 6, and 12 weeks. Significant time by group interactions
      emerged for appearance esteem and self-compassion, with appearance esteem and
      self-compassion increasing in the intervention relative to the control group.
      These findings provide preliminary support for BodiMojo, a cost-effective mobile
      app for positive body image.

PMID- 29349594
TI  - Pacifists and Revenge-Seekers in Response to Unambiguous Peer Provocation.
AB  - In order to better understand why some children retaliate when they feel provoked
      and others do not, the present study identified "pacifistically-oriented"
      children who made negative interpretations in response to unambiguous
      provocations, yet did not endorse revenge goals, and compared them to "revenge
      seeking" children who also made negative interpretations but did endorse revenge
      goals. Groups were identified based on seventh graders' (N = 367; 54.77% male;
      22.89% racial/ethnic minority) responses to hypothetical situations in which a
      peer excluded and insulted them. Comparing these groups revealed that Pacifists
      endorsed relationship-maintaining goals and emotion regulation goals more highly
      than Revenge-Seekers. Revenge-Seekers reported more anger and endorsed beliefs
      about negative reciprocity and aggression being legitimate more highly than
      Pacifists. Additionally, Revenge-Seekers were more disrespect sensitive than were
      Pacifists, based on a measure of vigilance for signs of disrespect and
      expectations that others would disrespect them. Together these findings point to
      social-cognitive and emotion-related processes that may inhibit revenge-seeking
      in unambiguous provocation situations, even when children interpret the peer's
      behavior quite negatively.

PMID- 29349595
TI  - The Development of a Nano-based Approach to Alleviate Cisplatin-Induced
      Ototoxicity.
AB  - Cisplatin-induced hearing loss is experienced by a high percentage of patients
      with squamous cell carcinoma undergoing cisplatin chemotherapy. A novel nano
      construct capable of sequestering extracellular cisplatin was developed to combat
      this problem. The nano-construct consisted of superparamagnetic iron oxide
      nanoparticles (SPIONs) entrapped within polymeric micelles, which were formed
      from a glutathione diethyl ester-conjugated amphiphilic diblock copolymer. The
      glutathione-micelles were analyzed at the cellular level and in an organotypic
      study for safety evaluation. All utilized methods indicated that the micelles do
      not cause cellular toxicity or organ damage. The micelles' ability to reduce
      cisplatin-induced cytotoxicity was then probed in an in vitro model. Cisplatin
      was pre-treated with the novel nano-construct before being added to growing
      cells. When compared to cells that were exposed to untreated cisplatin, cells in
      the pre-treated cisplatin group showed a significant increase in cell viability.
      This clearly demonstrates that the construct is able to protect the cells from
      cisplatin cytotoxicity and makes it highly likely that the novel nano-construct
      will be able to play a role in the protection of the inner ear from cisplatin
      induced ototoxicity.

PMID- 29349596
TI  - Concomitant Use of Antiplatelets and Anticoagulants in Patients with Coronary
      Heart Disease and Atrial Fibrillation: What Do Recent Clinical Trials Teach Us?
AB  - PURPOSE OF REVIEW: Coronary heart disease (CHD) and atrial fibrillation (AF) are
      among the most common cardiovascular diseases. A significant proportion of
      patients have both CHD and AF and are at increased risk for thrombotic
      complications. Current therapy for CHD and AF includes antiplatelet and
      anticoagulant medications, respectively. Patients with concurrent CHD and AF may
      be prescribed dual antiplatelet therapy (DAPT) in addition to anticoagulation,
      which increases their bleeding risk. Controversy remains on how to balance risks
      and benefits in patients with CHD and AF in which multiple antithrombotic
      therapies may be indicated. RECENT FINDINGS: We review clinical trials and
      current guidelines for antiplatelet and anticoagulant therapy in CHD and AF.
      Aspirin and P2Y12 inhibitors are the mainstay of antiplatelet therapy. Vitamin K
      antagonists (VKAs) are the most commonly used anticoagulant, although the use of
      non-VKA oral anticoagulants (NOACs) in patients with AF is increasing. Recent
      studies provide guidance on how to address antithrombotic therapies in patients
      with concomitant CHD and AF. To date, we have evidence that in patients with AF
      who undergo percutaneous coronary intervention (PCI), clopidogrel with VKA may be
      used safely without aspirin. Also, low-dose rivaroxaban in combination with
      either clopidogrel only or DAPT is as effective as the traditional regimen of
      triple therapy with VKA and DAPT with lower bleeding risk. Dabigatran with a
      P2Y12 inhibitor was also found to be safe with less bleeding compared to triple
      therapy with VKA and DAPT. Use of a single antiplatelet agent with
      anticoagulation has become a viable choice in patients with CHD and AF, but more
      clinical trial data is needed to confirm therapy and duration regimens.

PMID- 29349597
TI  - Drug repurposing screening identifies bortezomib and panobinostat as drugs
      targeting cancer associated fibroblasts (CAFs) by synergistic induction of
      apoptosis.
AB  - Cancer associated fibroblasts (CAFs) are the most abundant components of cancer
      microenvironment. They play important roles in cancer initiation, progression,
      and metastasis. In addition, CAFs can confer drug-resistance to cancer cells.
      Considering their pro-tumorigenic roles, it is recommended to remove CAFs to
      prevent cancer recurrence after chemotherapy. Despite their clinical
      significance, few anti-CAF drugs have been developed. The objective of this study
      was to find a drug that could suppress the viability of patient-derived CAFs
      through repurposed screening of 51 drugs that were in clinical trials or received
      FDA approval. As a result, bortezomib (BTZ), carfilzomib (CFZ), and panobinostat
      (PST) were identified as anti-CAF drug candidates. It was confirmed that BTZ and
      PST could decrease the viability of various patients derived CAFs through
      inducing of caspase-3 mediated apoptosis. Interestingly, combination therapy with
      BTZ and PST showed better efficacy of inhibiting CAFs than single treatment. The
      synergistic effect between BTZ and PST on viability of CAFs was observed both in
      vitro CAF culture and in vivo mouse model. Furthermore, combination therapy with
      BTZ/PST and conventional anticancer compound docetaxel strongly inhibited tumor
      growth in xenografts of mouse breast cancer cells with mouse CAFs. In conclusion,
      our present study revealed that BTZ and PST could significantly reduce the
      viability of CAFs. Therefore, a combination therapy with BTZ/PST and anticancer
      drugs might be considered as a new rational for the development of anticancer
      therapy.

PMID- 29349599
TI  - Evolution of Eukaryal and Archaeal Pseudouridine Synthase Pus10.
AB  - In archaea, pseudouridine (Psi) synthase Pus10 modifies uridine (U) to Psi at
      positions 54 and 55 of tRNA. In contrast, Pus10 is not found in bacteria, where
      modifications at those two positions are carried out by TrmA (U54 to m5U54) and
      TruB (U55 to Psi55). Many eukaryotes have an apparent redundancy; their genomes
      contain orthologs of archaeal Pus10 and bacterial TrmA and TruB. Although
      eukaryal Pus10 genes share a conserved catalytic domain with archaeal Pus10
      genes, their biological roles are not clear for the two reasons. First,
      experimental evidence suggests that human Pus10 participates in apoptosis induced
      by the tumor necrosis factor-related apoptosis-inducing ligand. Whether the
      function of human Pus10 is in place or in addition to of Psi synthesis in tRNA is
      unknown. Second, Pus10 is found in earlier evolutionary branches of fungi (such
      as chytrid Batrachochytrium) but is absent in all dikaryon fungi surveyed
      (Ascomycetes and Basidiomycetes). We did a comprehensive analysis of sequenced
      genomes and found that orthologs of Pus10, TrmA, and TruB were present in all the
      animals, plants, and protozoa surveyed. This indicates that the common eukaryotic
      ancestor possesses all the three genes. Next, we examined 116 archaeal and
      eukaryotic Pus10 protein sequences to find that Pus10 existed as a single copy
      gene in all the surveyed genomes despite ancestral whole genome duplications had
      occurred. This indicates a possible deleterious gene dosage effect. Our results
      suggest that functional redundancy result in gene loss or neofunctionalization in
      different evolutionary lineages.

PMID- 29349600
TI  - Beneficial Mutations from Evolution Experiments Increase Rates of Growth and
      Fermentation.
AB  - A major goal of evolutionary biology is to understand how beneficial mutations
      translate into increased fitness. Here, we study beneficial mutations that arise
      in experimental populations of yeast evolved in glucose-rich media. We find that
      fitness increases are caused by enhanced maximum growth rate (R) that come at the
      cost of reduced yield (K). We show that for some of these mutants, high R
      coincides with higher rates of ethanol secretion, suggesting that higher growth
      rates are due to an increased preference to utilize glucose through the
      fermentation pathway, instead of respiration. We examine the performance of
      mutants across gradients of glucose and nitrogen concentrations and show that the
      preference for fermentation over respiration is influenced by the availability of
      glucose and nitrogen. Overall, our data show that selection for high growth rates
      can lead to an enhanced Crabtree phenotype by the way of beneficial mutations
      that permit aerobic fermentation at a greater range of glucose concentrations.

PMID- 29349598
TI  - Phase Ib study evaluating safety and clinical activity of the anti-HER3 antibody
      lumretuzumab combined with the anti-HER2 antibody pertuzumab and paclitaxel in
      HER3-positive, HER2-low metastatic breast cancer.
AB  - : Purpose To investigate the safety and clinical activity of comprehensive human
      epidermal growth factor receptor (HER) family receptor inhibition using
      lumretuzumab (anti-HER3) and pertuzumab (anti-HER2) in combination with
      paclitaxel in patients with metastatic breast cancer (MBC). Methods This phase Ib
      study enrolled 35 MBC patients (first line or higher) with HER3-positive and HER2
      low (immunohistochemistry 1+ to 2+ and in-situ hybridization negative) tumors.
      Patients received lumretuzumab (1000 mg in Cohort 1; 500 mg in Cohorts 2 and 3)
      plus pertuzumab (840 mg loading dose [LD] followed by 420 mg in Cohorts 1 and 2;
      420 mg without LD in Cohort 3) every 3 weeks, plus paclitaxel (80 mg/m2 weekly in
      all cohorts). Patients in Cohort 3 received prophylactic loperamide treatment.
      Results Diarrhea grade 3 was a dose-limiting toxicity of Cohort 1 defining the
      maximum tolerated dose of lumretuzumab when given in combination with pertuzumab
      and paclitaxel at 500 mg every three weeks. Grade 3 diarrhea decreased from 50%
      (Cohort 2) to 30.8% (Cohort 3) with prophylactic loperamide administration and
      omission of the pertuzumab LD, nonetheless, all patients still experienced
      diarrhea. In first-line MBC patients, the objective response rate in Cohorts 2
      and 3 was 55% and 38.5%, respectively. No relationship between HER2 and HER3
      expression or somatic mutations and clinical response was observed. Conclusions
      Combination treatment with lumretuzumab, pertuzumab and paclitaxel was associated
      with a high incidence of diarrhea. Despite the efforts to alter dosing, the
      therapeutic window remained too narrow to warrant further clinical development.
      TRIAL REGISTRATION: on ClinicalTrials.gov with the identifier NCT01918254 first
      registered on 3rd July 2013.

PMID- 29349601
TI  - Prospective feasibility analysis of a novel off-line approach for MR-guided
      radiotherapy.
AB  - BACKGROUND: The present work aimed to analyze the feasibility of a shuttle-based
      MRI-guided radiation therapy (MRgRT) in the treatment of pelvic malignancies.
      PATIENTS AND METHODS: 20 patients with pelvic malignancies were included in this
      prospective feasibility analysis. Patients underwent daily MRI in treatment
      position prior to radiotherapy at the German Cancer Research Center. Positional
      inaccuracies, time and patient compliance were assessed for the application of
      off-line MRgRT. RESULTS: In 78% of applied radiation fractions, MR imaging for
      position verification could be performed without problems. Additionally,
      treatment-related side effects and reduced patient compliance were only
      responsible for omission of MRI in 9% of radiation fractions. The study workflow
      took a median time of 61 min (range 47-99 min); duration for radiotherapy alone
      was 13 min (range 7-26 min). Patient positioning, MR imaging and CT imaging
      including patient repositioning and the shuttle transfer required median times of
      10 min (range 7-14 min), 26 min (range 15-60 min), 5 min (range 3-8 min) and 8
      min (range 2-36 min), respectively. To assess feasibility of shuttle-based MRgRT,
      the reference point coordinates for the x, y and z axis were determined for the
      MR images and CT obtained prior to the first treatment fraction and correlated
      with the coordinates of the planning CT. In our dataset, the median positional
      difference between MR imaging and CT-based imaging based on fiducial matching
      between MR and CT imaging was equal to or less than 2 mm in all spatial
      directions. The limited space in the MR scanner influenced patient selection, as
      the bore of the scanner had to accommodate the immobilization device and the
      constructed stereotactic frame. Therefore, obese, extremely muscular or very tall
      patients could not be included in this trial in addition to patients for whom
      exposure to MRI was generally judged inappropriate. CONCLUSION: This trial
      demonstrated for the first time the feasibility and patient compliance of a
      shuttle-based off-line approach to MRgRT of pelvic malignancies.

PMID- 29349602
TI  - Does the interval from tumour surgery to radiotherapy influence survival in
      paediatric high grade glioma?
AB  - PURPOSE: Paediatric high grade glioma (pHGG) are rare. Following maximum safe
      resection, children >3 years with HGG receive radiotherapy as standard of care.
      Whether the interval from tumour surgery to radiotherapy (ISRT) influences
      survival is disputed in adults with glioblastoma, data for children are lacking.
      This retrospective single-centre analysis investigates a possible impact of ISRT
      on survival in paediatric patients with HGG. METHODS: Survival was analysed in
      patients aged 3-19 years with non-pontine HGG. RESULTS: Thirty-eight patients
      were included (female:male 19:19) with a median age of 11.0 years (3.4-17.7).
      Seventeen patients had grade 3 and 21 grade 4 glioma. Gross total resection was
      achieved in 26.3%, partial resection in 36.8% and 36.8% underwent biopsy only.
      All patients received concomitant and adjuvant chemotherapy. Fifty percent (n =
      19) started irradiation <=17 days (median interval 12 days [range 5-17]), 50%
      thereafter (median 28 days [range 19-78]). More patients with grade 4 tumours
      were irradiated shortly after surgery. ISRT (as a continuous variable and
      dichotomised into two groups by the median ISRT of 18 days) did not significantly
      influence overall survival (OS) or progression-free survival (PFS). Higher extent
      of resection (EOR), lower tumour grade as well as chemotherapy with temozolomide
      had a significant positive impact on OS and PFS in univariate analysis and
      (except for the effect of temozolomide on PFS) also in multivariable analysis.
      CONCLUSIONS: ISRT did not influence survival in pHGG. In view of upcoming
      targeted treatment options in pHGG the present data suggest that it is safe to
      perform molecular analyses within a 4-week timeframe before radiotherapy.

PMID- 29349603
TI  - Neoadjuvant chemoradiation for esophageal cancer : Surgery improves locoregional
      control while response based on FDG-PET/CT predicts survival.
AB  - INTRODUCTION: To retrospectively analyze the outcome of patients with esophageal
      cancer treated with neoadjuvant chemoradiation. METHODS: A total of 41 patients
      received neoadjuvant intent chemoradiation for esophageal cancer. Most patients
      had a locally advanced disease (T3/4: 82%, N+: 83%, M0: 100%) and squamous cell
      carcinoma (83%). All patients received concurrent chemotherapy with cisplatin/5
      fluorouracil or mitomycin/5-fluorouracil. Median radiation dose was 50.4 Gy in
      the 25 patients who proceeded to surgery and 57.4 Gy in 16 patients who did not
      undergo surgery. FDG-PET/CT was used for treatment planning in 24 patients. A
      second FDG-PET/CT was available for response evaluation in 18 patients. RESULTS:
      Median follow-up was 16 months in all patients and 30 months in survivors.
      Radiotherapy was completed without interruptions >3 days in 90% of patients, and
      chemotherapy was carried out to >80% in 85% of patients. The 2-year locoregional
      control rate was 60%, distant control rate 54% and overall survival rate 50%.
      Hematological toxicity grade 3/4 was observed in 34%/10% of patients and non
      hematological toxicity grade 3/4 in 46%/2% of patients. Perioperative 30-day
      mortality was 4%. Subgroup analyses revealed that surgery significantly improved
      locoregional control (74% vs. 39%, p = 0.034), but not the 2-year survival rate
      (54% vs. 43%, p = 0.246). In contrast, response based on FDG-PET/CT prior and
      after chemoradiation significantly predicted improved overall survival (2-year
      overall survival 61% vs. 40%, p = 0.048). CONCLUSION: Outcomes of our cohort were
      comparable to other series using similar treatments. Surgery significantly
      improved locoregional control but not survival. Response based on FDG-PET/CT
      predicted survival and might be used for treatment stratification.

PMID- 29349604
TI  - Quality of training in radiation oncology in Germany: where do we stand? :
      Results from a 2016/2017 survey performed by the working group "young DEGRO" of
      the German society of radiation oncology (DEGRO).
AB  - PURPOSE: To evaluate the current situation of young radiation oncologists in
      Germany with regard to the contents and quality of training and level of
      knowledge, as well as their working conditions and professional satisfaction.
      METHODS: From June 2016 to February 2017, a survey was conducted by the young
      DEGRO (yDEGRO) using an online platform. The questionnaire consisted of 28 items
      examining a broad range of aspects influencing residency. There were 96 completed
      questionnaires RESULTS: 83% of participants stated to be very or mostly pleased
      with their residency training. Moderate working hours and a good colleagueship
      contribute to a comfortable working environment. Level of knowledge regarding the
      most common tumor sites (i.e. palliative indications, lung, head and neck, brain,
      breast, prostate) was pleasing. Radiochemotherapy embodies a cornerstone in
      training. Modern techniques such as intensity-modulated radiotherapy (IMRT) and
      stereotactic procedures are now in widespread use. Education for rare indications
      and center-based procedures offers room for improvement. CONCLUSION: Radiation
      oncology remains an attractive and versatile specialty with favorable working
      conditions. Continuing surveys in future years will be a valuable measuring tool
      to set further priorities in order to preserve and improve quality of training.

PMID- 29349606
TI  - Well-Differentiated Liposarcoma (Atypical Lipomatous Tumor) Presenting as an
      Esophageal Polyp.

PMID- 29349605
TI  - Improved effectiveness of stereotactic radiosurgery in large brain metastases by
      individualized isotoxic dose prescription: an in silico study.
AB  - INTRODUCTION: In large brain metastases (BM) with a diameter of more than 2 cm
      there is an increased risk of radionecrosis (RN) with standard stereotactic
      radiosurgery (SRS) dose prescription, while the normal tissue constraint is
      exceeded. The tumor control probability (TCP) with a single dose of 15 Gy is only
      42%. This in silico study tests the hypothesis that isotoxic dose prescription
      (IDP) can increase the therapeutic ratio (TCP/Risk of RN) of SRS in large BM.
      MATERIALS AND METHODS: A treatment-planning study with 8 perfectly spherical and
      46 clinically realistic gross tumor volumes (GTV) was conducted. The effects of
      GTV size (0.5-4 cm diameter), set-up margins (0, 1, and 2 mm), and beam
      arrangements (coplanar vs non-coplanar) on the predicted TCP using IDP were
      assessed. For single-, three-, and five-fraction IDP dose-volume constraints of
      V12Gy = 10 cm3, V19.2 Gy = 10 cm3, and a V20Gy = 20 cm3, respectively, were used
      to maintain a low risk of radionecrosis. RESULTS: In BM of 4 cm in diameter, the
      maximum achievable single-fraction IDP dose was 14 Gy compared to 15 Gy for
      standard SRS dose prescription, with respective TCPs of 32 and 42%. Fractionated
      SRS with IDP was needed to improve the TCP. For three- and five-fraction IDP, a
      maximum predicted TCP of 55 and 68% was achieved respectively (non-coplanar beams
      and a 1 mm GTV-PTV margin). CONCLUSIONS: Using three-fraction or five-fraction
      IDP the predicted TCP can be increased safely to 55 and 68%, respectively, in
      large BM with a diameter of 4 cm with a low risk of RN. Using IDP, the
      therapeutic ratio of SRS in large BM can be increased compared to current SRS
      dose prescription.

PMID- 29349607
TI  - Molecular characterization of Fagaceae species using inter-primer binding site
      (iPBS) markers.
AB  - Retrotransposons (RTNs) contribute for genome evolution, influencing its size and
      structure. We investigated the utility of the RTN-based markers inter-primer
      binding site (iPBS) for the molecular characterization of 25 Fagaceae species
      from genera Castanea, Fagus and Quercus. The assessment of genetic diversity,
      relationships and structure, as well as taxonomic classification of Fagaceae
      based on molecular data is important for definition of conservation, forestry
      management strategies and discrimination among natural hybrids and their parents
      since natural hybridization may increase with the climate changes. Here, iPBS
      primers designed by other authors were tested alone and combined. Some of them
      were discriminative, revealed polymorphism within and among taxa allowing the
      production of a total of 150 iPBS markers. In addition, several monomorphic iPBS
      markers were also amplified in each taxon. The UPGMA dendrogram based on the
      pooled iPBS data revealed 27% of genetic similarity among species. The
      individuals were clustered per genus and most of the oaks per infrageneric group
      corroborating the adopted taxonomy. Globally, the iPBS markers demonstrated
      suitability for DNA fingerprinting, determination of phylogenies and taxonomic
      discrimination in Fagaceae, and could constitute a useful and alternative tool
      for germplasm characterization, and for definition of conservation strategies and
      forestry management. Moreover, these markers would be useful for fingerprinting
      natural hybrids that share morphological similarities with their parents. Since
      iPBS markers could also enable insights about RTNs evolution, an eventual
      correlation among iPBS polymorphism, variability of RTN insertions and/or genome
      size in Fagaceae is discussed.

PMID- 29349609
TI  - Caspase-1-Mediated Pyroptosis of the Predominance for Driving CD4[Formula: see
      text] T Cells Death: A Nonlocal Spatial Mathematical Model.
AB  - Caspase-1-mediated pyroptosis is the predominance for driving CD4[Formula: see
      text] T cells death. Dying infected CD4[Formula: see text] T cells can release
      inflammatory signals which attract more uninfected CD4[Formula: see text] T cells
      to die. This paper is devoted to developing a diffusive mathematical model which
      can make useful contributions to understanding caspase-1-mediated pyroptosis by
      inflammatory cytokines IL-1[Formula: see text] released from infected cells in
      the within-host environment. The well-posedness of solutions, basic reproduction
      number, threshold dynamics are investigated for spatially heterogeneous
      infection. Travelling wave solutions for spatially homogeneous infection are
      studied. Numerical computations reveal that the spatially heterogeneous infection
      can make [Formula: see text], that is, it can induce the persistence of virus
      compared to the spatially homogeneous infection. We also find that the random
      movements of virus have no effect on basic reproduction number for the spatially
      homogeneous model, while it may result in less infection risk for the spatially
      heterogeneous model, under some suitable parameters. Further, the death of
      infected CD4[Formula: see text] cells which are caused by pyroptosis can make
      [Formula: see text], that is, it can induce the extinction of virus, regardless
      of whether or not the parameters are spatially dependent.

PMID- 29349608
TI  - Comparative transcriptomics uncovers differences in photoautotrophic versus
      photoheterotrophic modes of nutrition in relation to secondary metabolites
      biosynthesis in Swertia chirayita.
AB  - Swertia chirayita is a high-value medicinal herb exhibiting antidiabetic,
      hepatoprotective, anticancer, antiediematogenic and antipyretic properties.
      Scarcity of its plant material has necessitated in vitro production of
      therapeutic metabolites; however, their yields were low compared to field grown
      plants. Possible reasons for this could be differences in physiological and
      biochemical processes between plants grown in photoautotrophic versus
      photoheterotrophic modes of nutrition. Comparative transcriptomes of S. chirayita
      were generated to decipher the crucial molecular components associated with the
      secondary metabolites biosynthesis. Illumina HiSeq sequencing yielded 57,460 and
      43,702 transcripts for green house grown (SCFG) and tissue cultured (SCTC)
      plants, respectively. Biological role analysis (GO and COG assignments) revealed
      major differences in SCFG and SCTC transcriptomes. KEGG orthology mapped 351 and
      341 transcripts onto secondary metabolites biosynthesis pathways for SCFG and
      SCTC transcriptomes, respectively. Nineteen out of 30 genes from primary
      metabolism showed higher in silico expression (FPKM) in SCFG versus SCTC,
      possibly indicating their involvement in regulating the central carbon pool. In
      silico data were validated by RT-qPCR using a set of 16 genes, wherein 10 genes
      showed similar expression pattern across both the methods. Comparative
      transcriptomes identified differentially expressed transcription factors and ABC
      type transporters putatively associated with secondary metabolism in S.
      chirayita. Additionally, functional classification was performed using NCBI
      Biosystems database. This study identified the molecular components implicated in
      differential modes of nutrition (photoautotrophic vs. photoheterotrophic) in
      relation to secondary metabolites production in S. chirayita.

PMID- 29349611
TI  - Abstracts of the 6th international multiple system atrophy congress.

PMID- 29349610
TI  - Ligand Binding Dynamics for Pre-dimerised G Protein-Coupled Receptor Homodimers:
      Linear Models and Analytical Solutions.
AB  - Evidence suggests that many G protein-coupled receptors (GPCRs) are bound
      together forming dimers. The implications of dimerisation for cellular signalling
      outcomes, and ultimately drug discovery and therapeutics, remain unclear.
      Consideration of ligand binding and signalling via receptor dimers is therefore
      required as an addition to classical receptor theory, which is largely built on
      assumptions of monomeric receptors. A key factor in developing theoretical models
      of dimer signalling is cooperativity across the dimer, whereby binding of a
      ligand to one protomer affects the binding of a ligand to the other protomer.
      Here, we present and analyse linear models for one-ligand and two-ligand binding
      dynamics at homodimerised receptors, as an essential building block in the
      development of dimerised receptor theory. For systems at equilibrium, we compute
      analytical solutions for total bound labelled ligand and derive conditions on the
      cooperativity factors under which multiphasic log dose-response curves are
      expected. This could help explain data extracted from pharmacological experiments
      that do not fit to the standard Hill curves that are often used in this type of
      analysis. For the time-dependent problems, we also obtain analytical solutions.
      For the single-ligand case, the construction of the analytical solution is
      straightforward; it is bi-exponential in time, sharing a similar structure to the
      well-known monomeric competition dynamics of Motulsky-Mahan. We suggest that this
      model is therefore practically usable by the pharmacologist towards developing
      insights into the potential dynamics and consequences of dimerised receptors.

PMID- 29349612
TI  - Dexamethasone-induced leukocytosis is associated with poor survival in newly
      diagnosed glioblastoma.
AB  - Despite its well-characterized side effects, dexamethasone is widely used in the
      pre-, peri- and postoperative neurosurgical setting due to its effective relief
      of tumor-induced symptoms through the reduction of tumor-associated edema.
      However, some patients show laboratory-defined dexamethasone induced elevation of
      white blood cell count, and its impact on glioblastoma progression is unknown. We
      retrospectively analyzed 113 patients with newly diagnosed glioblastoma to
      describe the incidence, risk factors and clinical features of dexamethasone
      induced leukocytosis in primary glioblastoma patients. We further conducted an
      immunohistochemical analysis of the granulocyte and lymphocyte tumor-infiltration
      in the available corresponding histological sections. Patient age was identified
      to be a risk factor for the development of dexamethasone-induced leukocytosis (p
      < 0.05). The presence of dexamethasone-induced leukocytosis decreased overall
      survival (HR 2.25 95% CI [1.15-4.38]; p < 0.001) and progression-free survival
      (HR 2.23 95% CI [1.09-4.59]; p < 0.01). Furthermore, patients with dexamethasone
      induced leukocytosis had significantly reduced CD15 + granulocytic- (p < 0.05)
      and CD3 + lymphocytic tumour infiltration (p < 0.05). We identified a subgroup of
      glioblastoma patients that are at particularly high risk for poor outcome upon
      dexamethasone treatment. Therefore, restrictive dosage or other edema reducing
      substances should be considered in patients with dexamethasone-induced
      leukocytosis.

PMID- 29349613
TI  - Tumor treating fields: a new approach to glioblastoma therapy.
AB  - Glioblastoma is an aggressive brain malignancy with poor outcomes. Current
      standard of care involves surgery, radiotherapy and chemotherapy. Even with
      optimal treatment, 5-year survival rates are low. Many patients are unable to
      tolerate the considerable side effects that therapy involves and suffer from low
      quality of life. Anti-mitotic tumor treating fields have shown potential in
      treating glioblastoma with data suggesting that they prolong disease-free
      survival and overall survival. Novocure has marketed a device that generates
      these fields via externally placed electrodes. Incorporation of electric field
      therapy into GBM treatment has been somewhat slow, due to concerns about cost,
      practicality of its usage from a patient perspective, and hesitation of the
      medical and scientific community to embrace its unconventional mechanism.
      However, clinical trials have demonstrated this therapy has relatively minor side
      effects and high patient compliance. In this review, we explore the current state
      of this technology and discuss the benefits and limitations of tumor treating
      fields.

PMID- 29349614
TI  - Treatment and outcomes of 28 patients with spinal metastasis from gynecological
      cancer.
AB  - The aim of this study was to provide some useful information concerning clinical
      characteristics, surgical treatment, potential contributing factor and prognostic
      factors for patients with gynecological cancer (GC) spinal metastasis. We
      reviewed 28 patients with GC spinal metastasis in our spine tumor center between
      July 2008 and July 2015. Surgeries were performed on 22 of them. Univariate and
      multivariate analyses were conducted to identify potential prognostic factors
      affecting spinal metastasis-free survival (SMFS) and overall survival. The
      operative patients responded favorably according to decrease of VAS score and
      increase of Frankel grade after surgery. The 1- and 2-year survival rates in all
      patients were 60.7 and 41.0%, respectively. Univariate analysis suggested that
      age at diagnosis with GC was the potential contributing factor for spinal
      metastasis, while Frankel grade, ECOG-PS, visceral metastasis and chemotherapy
      were the potential prognostic factors affecting survival. Multivariate analysis
      indicated that the independent prognostic factors came from visceral metastasis
      and chemotherapy. Surgery played an important role in improving patients' quality
      of life. Patients over 50 years old had a shorter SMFS after diagnosed with GC.
      Visceral metastasis was an adverse prognostic factor for patients with GC spinal
      metastasis, while chemotherapy was a favorable one.

PMID- 29349615
TI  - Long-term follow-up (at 5 years) of midline incisional hernia repairs using a
      primary closure and prosthetic onlay technique: recurrence and quality of life.
AB  - INTRODUCTION AND OBJECTIVES: The recurrence rate of incisional hernia (IH) repair
      is usually underestimated due to a lack of long-term follow-up. The objective of
      this study was to evaluate recurrence rate for patients operated on midline IH
      surgery, using a primary closure and prosthetic onlay technique, 5 years after
      the procedure. MATERIALS AND METHODS: From January 2009 to January 2011, all 92
      patients operated on elective midline IH repair by primary closure and prosthetic
      onlay technique in a General Surgery Department were retrospectively included in
      the study. Exclusion criteria were absence of follow-up or death. Recurrence rate
      and quality of life were assessed. Demographic, surgical data and quality of life
      in patients with and without 5-year recurrence were compared. RESULTS: Mean
      follow-up was 64 months. Ultimately, 76 patients were included in the study,
      representing 82% of the selected patients during the study period (76/92), of
      whom 24 presented a recurrence (32%). Half (12) were diagnosed for recurrence
      more than 3 years after the surgery. Patients who developed a recurrence had more
      percentage of obesity (64 vs. 29%, p = 0.016), which denoted an odds ratio (OR)
      for recurrence of 4.4 (1.2-15.7; p = 0.01) and they punctuated lower in quality
      of life (6.0 +/- 2.9 vs. 7.6 +/- 2.6, p = 0.006). CONCLUSIONS: Recurrence rate on
      midline IH repair is still a concern (32% at 5 years). It is advisable to look
      for other strategies and more efficient surgical techniques for IH surgery,
      especially in obese patients.

PMID- 29349616
TI  - Outcomes of utilizing absorbable mesh as an adjunct to posterior sheath closure
      during complex posterior component separation.
AB  - BACKGROUND: A minority of patients undergoing posterior component separation
      (PCS) have abdominal wall defects that preclude complete reconstruction of the
      visceral sac with native tissue. The use of absorbable mesh bridges (AMB) to span
      such defects has not been established. We hypothesized that AMB use during
      posterior sheath closure of PCS is safe and provides favorable outcomes. METHODS:
      We performed a retrospective review of consecutive patients undergoing PCS with
      AMB at two hernia centers. Main outcome measures included demographics,
      comorbidities, and post-operative complications. RESULTS: 36 patients were
      identified. Post-operative wound complications included five surgical site
      infections. At a median of 27 months, there were five recurrent hernias (13.9%),
      2 of which were parastomal, but no episodes of intestinal obstruction/fistula.
      CONCLUSIONS: Utilization of AMB for large posterior layer deficits results in
      acceptable rates of perioperative wound morbidity, effective PCS repairs, and
      does not increase intestinal morbidity or fistula formation.

PMID- 29349617
TI  - Use of venovenous ECMO for neonatal and pediatric ECMO: a decade of experience at
      a tertiary children's hospital.
AB  - BACKGROUND: Advances in extracorporeal membrane oxygenation (ECMO) have led to
      increased use of venovenous (VV) ECMO in the pediatric population. We present the
      evolution and experience of pediatric VV ECMO at a tertiary care institution.
      METHODS: A retrospective cohort study from 01/2005 to 07/2016 was performed,
      comparing by cannulation mode. Survival to discharge, complications, and
      decannulation analyses were performed. RESULTS: In total, 160 patients (105 NICU,
      55 PICU) required 13 +/- 11 days of ECMO. VV cannulation was used primarily in 83
      patients with 64% survival, while venoarterial (VA) ECMO was used in 77 patients
      with 54% survival. Overall, 74% of patients (n = 118) were successfully
      decannulated; 57% survived to discharge. VA ECMO had a higher rate of intra
      cranial hemorrhage than VV (22 vs 9%, p = 0.003). Sixteen VA patients (21%) had
      radiographic evidence of a cerebral ischemic insult. No cardiac complications
      occurred with the use of dual-lumen VV cannulas. There were no differences in
      complications (p = 0.40) or re-operations (p = 0.85) between the VV and VA
      groups. CONCLUSION: Dual-lumen VV ECMO can be safely performed with appropriate
      image guidance, is associated with a lower rate of intra-cranial hemorrhage, and
      may be the preferred first-line mode of ECMO support in appropriately selected
      NICU and PICU patients. LEVEL OF EVIDENCE: II.

PMID- 29349618
TI  - Respiratory Training Late After Fontan Intervention: Impact on Cardiorespiratory
      Performance.
AB  - Fontan palliation allows patients with "single ventricle" circulation to reach
      adulthood with an acceptable quality of life, although exercise tolerance is
      significantly reduced. To assess whether controlled respiratory training (CRT)
      increases cardiorespiratory performance. 16 Adolescent Fontan patients (age 17. 5
      +/- 3.8 years) were enrolled. Patients were divided into CRT group (n = 10) and
      control group (C group, n = 6). Maximal cardiopulmonary test (CPT) was repeated
      at the end of CRT in the CRT group and after an average time of 3 months in the C
      group. In the CRT group a CPT endurance was also performed before and after CRT.
      In the CRT group there was a significant improvement in cardiovascular and
      respiratory response to exercise after CRT. Actually, after accounting for
      baseline values, the CRT group had decreased breathing respiratory reserve (- 15,
      95% CI -22.3 to - 8.0, p = 0.001) and increased RR peak (+ 4.8, 95% CI 0.7-8.9, p
      = 0.03), VE peak (+ 13.7, 95% CI 5.6-21.7, p = 0.004), VO2 of predicted (+ 8.5,
      95% CI 0.1-17.0, p = 0.05), VO2 peak (+ 4.3, 95% CI 0.3 to 8.2, p = 0.04), and
      VO2 workslope (+ 1.7, 95% CI 0.3-3.1, p = 0.02) as compared to the control group.
      Moreover, exercise endurance time increased from 8.45 to 17.7 min (p = 0.01). CRT
      improves cardiorespiratory performance in post-Fontan patients leading to a
      better aerobic capacity.

PMID- 29349619
TI  - 1H, 15N, and 13C chemical shift assignments of the micelle immersed FAT C
      terminal (FATC) domains of the human protein kinases ataxia-telangiectasia
      mutated (ATM) and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) fused
      to the B1 domain of streptococcal protein G (GB1).
AB  - FAT C-terminal (FATC) is a circa 33 residue-long domain. It controls the kinase
      functionality in phosphatidylinositol-3 kinase-related kinases (PIKKs). Recent
      NMR- and CD-monitored interaction studies indicated that the FATC domains of all
      PIKKs can interact with membrane mimetics albeit with different preferences for
      membrane properties such as surface charge and curvature. Thus they may generally
      act as membrane anchoring unit. Here, we present the 1H, 15N, and 13C chemical
      shift assignments of the DPC micelle immersed FATC domains of the human PIKKs
      ataxia-telangiectasia mutated (ATM, residues 3024-3056) and DNA protein kinase
      catalytic subunit (DNA-PKcs, residues 4096-4128), both fused to the 56 residue
      long B1 domain of Streptococcal protein G (GB1). Each fusion protein is 100 amino
      acids long and contains in the linking region between the GB1 tag and the FATC
      region a thrombin (LVPRGS) and an enterokinase (DDDDK) protease site. The
      assignments pave the route for the detailed structural characterization of the
      membrane mimetic bound states, which will help to better understand the role of
      the proper cellular localization at membranes for the function and regulation of
      PIKKs. The chemical shift assignment of the GB1 tag is useful for NMR
      spectroscopists developing new experiments or using GB1 otherwise for case
      studies in the field of in-cell NMR spectroscopy or protein folding. Moreover it
      is often used as purification tag. Earlier we showed already that GB1 does not
      interact with membrane mimetics and thus does not disturb the NMR monitoring of
      membrane mimetic interactions of attached proteins.

PMID- 29349620
TI  - Fatal Talaromyces marneffei Infection in a Patient with Autoimmune Hepatitis.
AB  - Talaromyces marneffei, previously known as Penicillium marneffei, is the most
      important pathogenic thermally dimorphic fungus causing systemic mycosis in
      Southeast Asia. Traditionally, T. marneffei infection in human was mainly
      associated with acquired immunodeficiency syndrome caused by HIV infection. In
      recent years, there has been an increasing number of T. marneffei infections
      reported in non-HIV-infected patients with other immunocompromised conditions,
      including autoantibodies against interferon-gamma, systemic lupus erythematosis,
      solid organ transplantation, Job's syndrome, hematological malignancies, and use
      of novel targeted therapies. In this article, we describe the first case of fatal
      T. marneffei infection in a patient with underlying autoimmune hepatitis,
      presented as fever without localizing features. The diagnosis of talaromycosis
      was confirmed with the identification of the fungi isolated from the blood
      culture specimen by conventional methods and using matrix-assisted laser
      desorption-ionization time-of-flight mass spectrometer. This case shows the
      importance of a high index of suspicion, particularly for such a highly fatal but
      potentially treatable fungal infection.

PMID- 29349621
TI  - Adsorption and leaching of novel fungicide pyraoxystrobin on soils by 14C tracing
      method.
AB  - Pyraoxystrobin, (E)-2-(2-((3-(4-chlorophenyl)-1-methyl-1H-pyrazole-5
      yloxy)methyl)phenyl)-3-methoxyacrylate, is a newly developed strobilurin
      fungicide with high antifungal efficiency. It has high potential to enter soil
      environments that might subsequently impact surface and groundwater. Therefore,
      14C-labeled pyraoxystrobin was used as a tracer to study the
      adsorption/desorption and migration behavior of this compound under laboratory
      conditions in three typical agricultural soils. The adsorption isotherms
      conformed with the Freundlich equation. Single factor analysis showed that
      organic matter content was the most important factor influencing the adsorption.
      The highest adsorption level was measured in soil with low pH and high organic
      carbon content. Once adsorbed, only 2.54 to 6.41% of the adsorbed compound could
      be desorbed. In addition, the mobility results from thin-layer chromatography and
      column leaching studies showed that it might be safe to use pyraoxystrobin as a
      fungicide without causing groundwater pollution from both runoff and leaching,
      which might be attributed to its strong hydrophobicity. High organic matter
      content enhanced pyraoxystrobin adsorption and desorption because of the rule of
      similarity (lipid solubility). In the column leaching study, 95.02% (minimum
      value) of the applied 14C remained within the upper 4.0-cm layer after 60 days.

PMID- 29349622
TI  - Transfusion practice patterns in patients with anemia receiving myelosuppressive
      chemotherapy for nonmyeloid cancer: results from a prospective observational
      study.
AB  - PURPOSE: The decision to prescribe packed red blood cell (PRBC) transfusions in
      patients with chemotherapy-induced anemia (CIA) includes assessment of clinical
      features such as the patient's cancer type and treatment regimen, severity of
      anemia symptoms, and presence of comorbidities. We examined contemporary
      transfusion practices in patients with nonmyeloid cancer and CIA. METHODS: Key
      inclusion criteria were age >= 18 years with nonmyeloid cancer, receiving
      first/second-line myelosuppressive chemotherapy, baseline hemoglobin (Hb) <= 10.0
      g/dL, and planned to receive >= 1 PRBC transfusions. Exclusion criteria were
      receipt of erythropoiesis-stimulating agents within 8 weeks of screening and/or
      chronic renal insufficiency. Data were collected from patients' medical records,
      laboratory values, and physician/provider questionnaires. Proportion of patients
      for each clinical consideration leading to a decision to prescribe a PRBC
      transfusion and 95% exact binomial confidence intervals were determined. RESULTS:
      The study enrolled 154 patients at 18 sites in USA; 147 (95.5%) received a PRBC
      transfusion. Fatigue was the most common symptom affecting the decision to
      prescribe a PRBC transfusion (101 [69.2%] patients). Of the three reasons
      selected as primary considerations for prescribing a PRBC transfusion, anemia
      symptoms (106 [72.1%] patients) was the most frequently reported, followed by Hb
      value (37 [25.2%] patients) and medical history (4 [2.7%] patients). CONCLUSIONS:
      In this study, the primary consideration for prescribing a PRBC transfusion was
      anemia symptoms in 72.1% of patients, with only 25.2% of patients prescribed a
      transfusion based exclusively on Hb value. Results indicate that clinical
      judgment and patient symptoms, not just Hb value, were used in decisions to
      prescribe PRBC transfusions.

PMID- 29349624
TI  - Combined effects of aspirin and vitamin D3 on two OSCC cell lines: a preliminary
      study.
AB  - OBJECTIVES: We evaluated the potential effects of aspirin combined with vitamin
      D3 on cell proliferation and apoptosis in oral cancer cells. RESULTS: Compared to
      the untreated control or individual drug, the combinations of aspirin and vitamin
      D3 significantly decreased the rates of cell proliferation by CCK-8 assay, and
      caused higher rates of cell apoptosis in both CAL-27 and SCC-15 cells by Annexin
      V-FITC apoptosis assay and flow cytometry. Remarkably, the combined treatment
      with aspirin and vitamin D3 significantly suppressed the expression of Bcl-2
      protein and p-Erk1/2 protein, examined by western blot analysis. CONCLUSIONS: Our
      study demonstrates that aspirin and vitamin D3 have biological activity against
      two human OSCC cell lines and their activity is synergistic or additive when two
      drugs used in combination with therapeutic concentrations. The combination of
      aspirin and vitamin D3 may be an effective approach for inducing cell death in
      OSCC.

PMID- 29349623
TI  - The association between Toxoplasma gondii infection and hypertensive disorders in
      T2DM patients: a case-control study in the Han Chinese population.
AB  - Type 2 diabetes mellitus (T2DM) is a major global health problem. The rate of
      infection with Toxoplasma gondii (T. gondii) is more than one-third of the total
      world population. The effects of T. gondii infection on the risk of diabetic
      complications and comorbidities are unclear. This study aims to determine the
      relationship between T. gondii infection and complications of T2DM in the Han
      Chinese population. We collected 1580 blood samples from T2DM patients and
      measured the levels of specific IgG antibodies against T. gondii in the sera of
      these patients using an ELISA assay. A logistic regression analysis was performed
      to estimate the effect of T. gondii infection on the complications of T2DM, while
      adjusting for age, gender, and triglyceride level (TG). We applied the
      multifactor dimensionality reduction (MDR) method to detect the interactions
      between T. gondii infections, demographic indexes and biochemical indicators
      among the different complications. Gender (the odds ratio (OR) = 0.63, 95%CI
      =0.45-0.89, P = 0.008) and TG level (OR = 0.64, 95%CI =0.45-0.89, P = 0.009) were
      influencing factors in T. gondii infections. T2DM patients who were infected with
      T. gondii had a 2.34 times risk of developing hypertension than those patients
      without T. gondii infection (OR = 2.34, 95%CI = 1.12-4.88, P = 0.024). The
      multiplicative interaction analysis and the additive interaction analysis did not
      reveal any evidence of interactive effects on diabetic complications and
      comorbidities. T. gondii might be a factor associated with hypertension in T2DM
      patients.

PMID- 29349625
TI  - Enhancement of the thermal and alkaline pH stability of Escherichia coli lysine
      decarboxylase for efficient cadaverine production.
AB  - OBJECTIVE: To enhance the thermal and alkaline pH stability of the lysine
      decarboxylase from Escherichia coli (CadA) by engineering the decameric interface
      and explore its potential for industrial applications. RESULTS: The mutant T88S
      was designed for improved structural stability by computational analysis. The
      optimal pH and temperature of T88S were 7.0 and 55  degrees C (5.5 and 50 
      degrees C for wild-type). T88S showed higher thermostability with a 2.9-fold
      increase in the half-life at 70  degrees C (from 11 to 32 min) and increased
      melting temperature (from 76 to 78  degrees C). Additionally, the specific
      activity and pH stability (residual activity after 10 h incubation) of T88S at pH
      8.0 were increased to 164 U/mg and 78% (58 U/mg and 57% for wild-type). The
      productivity of cadaverine with T88S (284 g L-lysine L-1 and 5 g DCW L-1) was 40
      g L-1 h-1, in contrast to 28 g L-1 h-1 with wild-type. CONCLUSION: The mutant
      T88S showed high thermostability, pH stability, and activity at alkaline pH,
      indicating that this mutant is a promising biocatalyst for industrial production
      of cadaverine.

PMID- 29349626
TI  - A two-stage system coupling hydrolytic acidification with algal microcosms for
      treatment of wastewater from the manufacture of acrylonitrile butadiene styrene
      (ABS) resin.
AB  - OBJECTIVES: To demonstrate the effectiveness of a novel two-stage system coupling
      hydrolytic acidification with algal microcosms for the treatment of acrylonitrile
      butadiene styrene (ABS) resin-manufacturing wastewater. RESULTS: After hydrolytic
      acidification, the BOD5/COD ratio increased from 0.22 to 0.56, showing improved
      biodegradability of the wastewater. Coupled with hydrolytic acidification, the
      algal microcosms showed excellent capability of in-depth removal of COD, NH3-N
      and phosphorus with removal rates 83, 100, and 89%, respectively, and aromatic
      pollutants, including benzene, were almost completely removed. The biomass
      concentration of Chlorella sp. increased from 5 * 106 to 2.1 * 107 cells/ml after
      wastewater treatment. CONCLUSIONS: This two-stage coupling system achieved deep
      cleaning of the benzene-containing petrochemical wastewater while producing
      greater algae biomass resources at low cost.

PMID- 29349627
TI  - Modeling and simulation of enzymatic gluconic acid production using immobilized
      enzyme and CSTR-PFTR circulation reaction system.
AB  - OBJECTIVES: Production of gluconic acid by using immobilized enzyme and
      continuous stirred tank reactor-plug flow tubular reactor (CSTR-PFTR) circulation
      reaction system. RESULTS: A production system is constructed for gluconic acid
      production, which consists of a continuous stirred tank reactor (CSTR) for pH
      control and liquid storage and a plug flow tubular reactor (PFTR) filled with
      immobilized glucose oxidase (GOD) for gluconic acid production. Mathematical
      model is developed for this production system and simulation is made for the
      enzymatic reaction process. The pH inhibition effect on GOD is modeled by using a
      bell-type curve. CONCLUSIONS: Gluconic acid can be efficiently produced by using
      the reaction system and the mathematical model developed for this system can
      simulate and predict the process well.

PMID- 29349628
TI  - Serum Total Magnesium Level and its Correlation with Symptom Control in Children
      with Mild Persistent Asthma.
AB  - OBJECTIVES: To determine the prevalence of hypomagnesemia in children with mild
      persistent asthma and to correlate the serum magnesium levels with symptom
      control in the above children. METHODS: It was a cross sectional study carried
      out from 1st April 2015 to 31st July 2016 at the department of Pediatrics, JIPMER
      Hospital. Participants included six to 12-y-old children with mild persistent
      asthma registered at childhood asthma clinic. Pulmonary function tests were done
      in all children using Care fusion Jaeger spirometer. Symptom control was assessed
      by childhood asthma control test questionnaire and the asthma control test
      questionnaire (ACT) score. Serum magnesium was measured using photometric method.
      Proportion of children with well controlled, partially controlled and poorly
      controlled asthma, serum magnesium levels across the three levels of control and
      correlation of serum magnesium level with ACT score and pulmonary function tests
      were studied. RESULTS: The prevalence of hypomagnesemia in children with mild
      persistent asthma was 5.6%. The median serum magnesium level was 2.0 mg/dl (IQR
      1.9-2.1 mg/dL). As assessed by the ACT score, 66% had well controlled, 23% had
      partially controlled and 11% had poorly controlled asthma. There was no
      significant difference in the serum magnesium levels in the above three groups.
      There was no significant correlation between serum magnesium levels and ACT score
      as well as pulmonary function tests. CONCLUSIONS: The prevalence of
      hypomagnesemia in the index study is much lower than earlier studies and there
      seems to be no significant association between serum magnesium levels and asthma
      symptom control.

PMID- 29349629
TI  - Cerebellum: from Development to Disease-the 8th International Symposium of the
      Society for Research on the Cerebellum and Ataxias.
AB  - In recent years, there has been tremendous growth in research on cerebellar motor
      and non-motor functions. Cerebellum is particularly involved in the spectrum of
      neurodevelopmental diseases. The 8th International Symposium of the Society for
      Research on the Cerebellum and Ataxia (SRCA) was held in Winnipeg, Manitoba,
      (Canada) on May 24-26, 2017. The main theme of the 8th International Symposium
      was "Development of the Cerebellum and Neurodevelopmental Disorders." Advances in
      genetics, epigenetic, cerebellar neurogenesis, axonogenesis and gliogenesis,
      cerebellar developmental disorders including autism spectrum disorders (ASD),
      neuroimaging, cerebellar ataxias, medulloblastoma, and clinical investigation of
      cerebellar diseases were presented. The goal of this symposium was to provide a
      platform to discuss cutting-edge knowledge while allowing researchers and
      trainees the opportunity to share and discuss their front-line research and ideas
      with others in the field, make connections, and strengthen international
      collaborations. The Ferdinando Rossi lecture was delivered by Dr. Richard Hawkes
      on the topic of patterning of the cerebellar cortex. This symposium emphasized
      the major importance of the involvement of the cerebellum in neurodevelopmental
      diseases from the clinical, radiological, biological, and genetic standpoint.

PMID- 29349630
TI  - Developmental Changes in Serotonergic Modulation of GABAergic Synaptic
      Transmission and Postsynaptic GABAA Receptor Composition in the Cerebellar
      Nuclei.
AB  - Outputs from the cerebellar nuclei (CN) are important for generating and
      controlling movement. The activity of CN neurons is controlled not only by
      excitatory inputs from mossy and climbing fibers and by gamma-aminobutyric acid
      (GABA)-based inhibitory transmission from Purkinje cells in the cerebellar cortex
      but is also modulated by inputs from other brain regions, including serotonergic
      fibers that originate in the dorsal raphe nuclei. We examined the modulatory
      effects of serotonin (5-HT) on GABAergic synapses during development, using rat
      cerebellar slices. As previously reported, 5-HT presynaptically decreased the
      amplitudes of stimulation-evoked inhibitory postsynaptic currents (IPSCs) in CN
      neurons, with this effect being stronger in slices from younger animals
      (postnatal days [P] 11-13) than in slices from older animals (P19-21). GABA
      release probabilities accordingly exhibited significant decreases from P11-13 to
      P19-21. Although there was a strong correlation between the GABA release
      probability and the magnitude of 5-HT-induced inhibition, manipulating the
      release probability by changing extracellular Ca2+ concentrations failed to
      control the extent of 5-HT-induced inhibition. We also found that the IPSCs
      exhibited slower kinetics at P11-13 than at P19-21. Pharmacological and molecular
      biological tests revealed that IPSC kinetics were largely determined by the
      prevalence of alpha1 subunits within GABAA receptors. In summary, pre- and
      postsynaptic developmental changes in serotonergic modulation and GABAergic
      synaptic transmission occur during the second to third postnatal weeks and may
      significantly contribute to the formation of normal adult cerebellar function.

PMID- 29349631
TI  - Promoter analysis of the fish gene of slow/cardiac-type myosin heavy chain
      implicated in specification of muscle fiber types.
AB  - Vertebrate skeletal muscles consist of heterogeneous tissues containing various
      types of muscle fibers, where specification of the fiber type is crucial for
      muscle development. Fish are an attractive experimental model to study the
      mechanisms of such fiber type specification because of the separated localization
      of slow and fast muscles in the trunk myotome. We examined regulation of
      expression of the torafugu gene of slow/cardiac-type myosin heavy chain, MYH M5 ,
      and isolated an operational promoter in order to force its tissue-specific
      expression across different fish species via the transgenic approach in zebrafish
      and medaka. This promoter activity was observed in adaxial cell-derived
      superficial slow muscle fibers under the control of a hedgehog signal. We also
      uncovered coordinated expression of MYH M5 and Sox6b, which is an important
      transcriptional repressor for specification of muscle fiber types and
      participates in hedgehog signaling. Sequence comparison in the 5'-flanking region
      identified three conserved regions, CSR1-CSR3, between torafugu MYH M5 and its
      zebrafish ortholog. Analysis of deletion mutants showed that CSR1 significantly
      stimulates gene expression in slow muscle fibers. In contrast, deletion of CSR3
      resulted in ectopic expression of a reporter gene in fast muscle fibers. CSR3 was
      found to contain a putative Sox family protein-binding site. These results
      indicate that the dual mechanism causing inhibition in fast muscle fibers and
      activation in slow muscle fibers is essential for slow muscle fiber-specific gene
      expression in fish.

PMID- 29349632
TI  - Growth performance and protective effect of vitamin E on oxidative stress
      pufferfish (Takifugu obscurus) following by ammonia stress.
AB  - This study was conducted to determine the effects of vitamin E on growth
      performance, biochemical parameters, and antioxidant capacity of pufferfish
      (Takifugu obscurus) exposed to ammonia stress. The experimental basal diets
      supplemented with vitamin E at the rates of 2.31 (control), 21.84, 40.23, 83.64,
      158.93, and 311.64 mg kg-1 dry weight were fed to fish for 60 days. After the
      feeding trial, the fish were exposed to 100 mg L-1 ammonia-nitrogen for 48 h. The
      results shown that the vitamin E group significantly improved weight gain,
      specific growth rate, and the expression levels of growth hormone receptors and
      insulin-like growth factor. Fish fed with the vitamin E-supplemented diets could
      increase plasma alkaline phosphatase activities and decrease plasma
      glutamicoxalacetic transaminase and glutamic-pyruvic transaminase activities. The
      relative expression levels of heat shock proteins (40.23-311.64 mg kg-1 vitamin E
      diet group), manganese superoxide dismutase (83.64-158.93 mg kg-1 vitamin E diet
      group), catalase (40.23-311.64 mg kg-1 vitamin E diet group), and glutathione
      reductase (40.23-311.64 mg kg-1 vitamin E diet group) were upregulated. On the
      other hand, the decreased level of reactive oxygen species (ROS) was observed in
      the 83.64-311.64 mg kg-1 vitamin E additive group. These results showed that
      vitamin E might have a potentially useful role as an effective antioxidant to
      improve resistance in pufferfish.

PMID- 29349634
TI  - Donor Cell-Derived Chronic Myeloproliferative Disease with t(7;11)(p15;p15) after
      Cord Blood Transplantation in a Patient with Philadelphia Chromosome-Positive
      Acute Lymphoblastic Leukemia.
AB  - We report a case of donor cell-derived chronic myeloproliferative disease with
      t(7;11)(p15;p15) occurring after cord blood transplantation (CBT). A 41-year-old
      man developed precursor B-cell acute lymphoblastic leukemia with a karyotype of
      46, XY, t(9;22)(q34;q11) and inv(9)(p11;q13), for which he received CBT from a
      sex-mismatched donor at the first complete remission of the leukemia. Five months
      after CBT, gradual neutrophilia of unknown origin developed following the myeloid
      reconstitution after CBT. Karyotyping of bone marrow cells at 9 months after CBT
      showed 46,XX, t(7;11)(p15;p15) in 17/20 dividing cells, but neither Philadelphia
      chromosome (Ph) nor inv(9)(p11;q13) was present. This is the first report of
      chronic myeloproliferative disease with t(7;11)(p15;p15) that developed in donor
      cells after CBT. The donor was well-developed and healthy, at least at the time
      of follow-up, half a year after the birth.

PMID- 29349633
TI  - Effects of tetradecylthioacetic acid (TTA) treatment on lipid metabolism in
      salmon hearts-in vitro and in vivo studies.
AB  - In intensive farming of Atlantic salmon, a large proportion of observed mortality
      is related to cardiovascular diseases and circulatory failure, indicating
      insufficient robustness and inadequate cardiac performance. This paper reports on
      the use of tetradecylthioacetic acid (TTA) where the main objective was to
      enhance utilisation of fatty acids (FA), considered the main energy source of the
      heart. In this study, three experiments were conducted: (I) an in vivo study
      where salmon post-smolt were administrated dietary TTA in sea, (II) an in vitro
      study where isolated salmon heart cells were pre-stimulated with increasing doses
      of TTA and (III) an in vivo experiment where salmon post-smolt were subjected to
      injections with increasing doses of TTA. In study I, TTA-treated fish had a
      smaller decrease in heart weight relative to fish bodyweight (CSI) in a period
      after sea transfer compared to the control. This coincided with lowered condition
      factor and muscle fat in the TTA-treated fish, which may indicate a higher
      oxidation of lipids for energy. In study II, the isolated hearts treated with the
      highest dose of TTA had higher uptake of radiolabelled FA and formation of CO2
      and acid-soluble products. In study III, expression of genes regulating
      peroxisomal FA oxidation, cell growth, elongation and desaturation were
      upregulated in the heart of TTA injected salmon. In contrast, genes involved in
      FA transport into the mitochondria were not influenced. In conclusion, these
      experiments indicate that TTA enhances energy production in salmon hearts by
      stimulation of FA oxidation.

PMID- 29349635
TI  - The diving reflex and asphyxia: working across species in physiological ecology.
AB  - Beginning in the mid-1930s the comparative physiologists Laurence Irving and Per
      Fredrik (Pete) Scholander pioneered the study of diving mammals, particularly
      harbor seals. Although resting on earlier work dating back to the late nineteenth
      century, their research was distinctive in several ways. In contrast to medically
      oriented physiology, the approaches of Irving and Scholander were strongly
      influenced by natural history, zoology, ecology, and evolutionary biology. Diving
      mammals, they argued, shared the cardiopulmonary physiology of terrestrial
      mammals, but evolution had modified these basic adaptive processes in extreme
      ways. In particular, seals' remarkable ability to hold breath, lower metabolism,
      produce energy anaerobically, and resist asphyxiation, provided a sharp contrast
      with terrestrial mammals, including humans. This diving physiology was an extreme
      elaboration of a general regulatory mechanism that allowed seals and other diving
      mammals to remain active underwater for extended periods. The decrease in heart
      rate referred to as bradycardia or the "diving reflex" was highly developed in
      diving mammals, but also found in less developed form in many other organisms
      faced by asphyxia. It therefore served as a kind of "master switch" for lowering
      metabolism in diving, hibernation, parturition, drowning, and other physiological
      responses involving lack of oxygen. Studying bradycardia unified a wide diversity
      of physiological phenomena, while also providing a context for contrasting the
      physiological responses of various species, including humans. Conducted in the
      laboratory and the field, this research served as a bridge between a comparative
      physiological ecology focused on non-human species and a human-centered general
      physiology.

PMID- 29349636
TI  - Effects of Asymmetric Local Joule Heating on Silicon Nanowire-Based Devices
      Formed by Dielectrophoresis Alignment Across Pt Electrodes.
AB  - We demonstrate the fabrication and characterization of silicon nanowire-based
      devices in metal-nanowire-metal configuration using direct current
      dielectrophoresis. The current-voltage characteristics of the devices were found
      rectifying, and their direction of rectification could be determined by voltage
      sweep direction due to the asymmetric Joule heating effect that occurred in the
      electrical measurement process. The photosensing properties of the rectifying
      devices were investigated. It reveals that when the rectifying device was in
      reverse-biased mode, the excellent photoresponse was achieved due to the strong
      built-in electric field at the junction interface. It is expected that rectifying
      silicon nanowire-based devices through this novel and facile method can be
      potentially applied to other applications such as logic gates and sensors.

PMID- 29349637
TI  - Association between keeping home records of catheter exit-site and incidence of
      peritoneal dialysis-related infections.
AB  - PURPOSE: To prevent peritoneal dialysis (PD)-related infection, components of
      self-catheter care have been emphasized. However, studies on the effectiveness of
      home recording for the prevention of PD-related infections are limited. This
      study aimed to examine the association between keeping home records of catheter
      exit site and incidence of PD-related infections. METHODS: Home record books were
      submitted by patients undergoing PD. The proportion of days on which exit-site
      home recording was carried out for 120 days (0-100%) was obtained. The patients
      were divided into the frequent home recording group (>= 40.5%; median value) and
      the infrequent home recording group (< 40.5%). The associations between the
      recording group and the incidence rate ratios (IRRs) of PD-related infections
      were estimated via negative binomial regression models. RESULTS: A total of 67
      patients participated in this study (mean age, 66.7 years). The incidence rates
      for exit-site infection, tunnel infection, and peritonitis were 0.42, 0.22, and
      0.06 times/patient-year, respectively. The IRRs of the frequent versus infrequent
      home recording groups for PD-related infection were 1.58 (95% confidence interval
      [CI], 0.72-3.46) in the univariate analysis and 1.49 (95% CI, 0.65-3.42) in the
      multivariate analysis. The IRRs of the frequent versus infrequent home recording
      groups for composite of surgery to create a new exit site and removal of PD
      catheter were 0.55 (95% CI, 0.78-3.88) and 0.35 (95% CI, 0.06-1.99),
      respectively. CONCLUSIONS: This study could not prove that keeping home records
      of patients' catheter exit site is associated with a lower incidence of PD
      related infections.

PMID- 29349638
TI  - Innovation in 3D Echocardiographic Imaging.
AB  - PURPOSE OF REVIEW: The purpose of this review is to detail three-dimensional
      echocardiographic (3DE) innovations in pre-surgical planning of congenital heart
      disease, guidance of catheter interventions such as fusion imaging, and
      functional assessment of patients with congenital heart disease. RECENT FINDINGS:
      Innovations in 3DE have helped us delineate the details of atrioventricular valve
      function and understand the mechanism of atrioventricular valve failure in
      patients with atrioventricular septal defect and single ventricle post repair.
      Advancement in holographic display of 3D datasets allows for better manipulation
      of 3D images in three dimensions and better understanding of anatomic
      relationships. 3DE with fusion imaging reduces radiation in catheter
      interventions and provides presentations of 3DE images in the similar fashion as
      the fluoroscopic images to improve communication between cardiologists. Lastly,
      3DE allows for quantitative ventricular volumetric and functional assessment.
      Recent innovations in 3DE allow for pre-surgical planning for congenital heart
      disease, reduce radiation using fusion imaging in catheter interventions, and
      enable accurate assessment of ventricular volume and function without geometric
      assumptions.

PMID- 29349640
TI  - Medical Cytogenetics : Reviewed by Shinichi Misawa.

PMID- 29349641
TI  - Thrombosis and Antithrombotic Therapy : Reviewed by Shinsaku Hirosawa.

PMID- 29349639
TI  - Outcomes in syncope research: a systematic review and critical appraisal.
AB  - Syncope is the common clinical manifestation of different diseases, and this
      makes it difficult to define what outcomes should be considered in prognostic
      studies. The aim of this study is to critically analyze the outcomes considered
      in syncope studies through systematic review and expert consensus. We performed a
      systematic review of the literature to identify prospective studies enrolling
      consecutive patients presenting to the Emergency Department with syncope, with
      data on the characteristics and incidence of short-term outcomes. Then, the
      strengths and weaknesses of each outcome were discussed by international syncope
      experts to provide practical advice to improve future selection and assessment.
      31 studies met our inclusion criteria. There is a high heterogeneity in both
      outcome choice and incidence between the included studies. The most commonly
      considered 7-day outcomes are mortality, dysrhythmias, myocardial infarction,
      stroke, and rehospitalisation. The most commonly considered 30-day outcomes are
      mortality, haemorrhage requiring blood transfusion, dysrhythmias, myocardial
      infarction, pacemaker or implantable defibrillator implantation, stroke,
      pulmonary embolism, and syncope relapse. We present a critical analysis of the
      pros and cons of the commonly considered outcomes, and provide possible solutions
      to improve their choice in ED syncope studies. We also support global initiatives
      to promote the standardization of patient management and data collection.

PMID- 29349643
TI  - A congenitally hypothyroid young man (Seated Dwarf, Goya's Studio, 19th century).

PMID- 29349642
TI  - Increased serum periostin concentrations are associated with the presence of
      diabetic retinopathy in patients with type 2 diabetes mellitus.
AB  - PURPOSE: To determine the association between serum periostin and the presence of
      diabetic retinopathy (DR). METHODS: Serum periostin was detected in 114 healthy
      subjects, 122 patients with type 2 diabetes mellitus (T2DM) and 159 patients with
      DR and compared among groups. Clinical data and other laboratory measurements
      such as glycated hemoglobin (HbA1c), lipid profiles, serum creatinine (Cr) and
      high-sensitivity CRP (hsCRP) were also collected and compared among groups. For
      subgroup analysis, patients with DR were divided into a non-proliferated diabetic
      retinopathy (NPDR) group and a proliferated diabetic retinopathy (PDR) group.
      Multivariate analysis was performed using logistic regression models. RESULTS:
      The serum periostin level was significantly higher in patients with diabetic
      retinopathy compared with healthy subjects and patients with T2DM (both P <
      0.001, respectively). Also, the periostin level was significantly higher in the
      PDR group compared to the NPDR group (P = 0.044). Multivariate logistic
      regression revealed that serum periostin was independently associated with the
      presence of DR in patients with T2DM (P < 0.001). The receiver operating
      characteristic (ROC) curves for DR development using serum periostin showed that
      the area under the receiver operating characteristic curves (AUC) was 0.838 (P <
      0.001). CONCLUSIONS: The current study demonstrated that serum periostin is
      significantly associated with the presence of DR in patients with T2DM and is an
      independent risk factor of DR.

PMID- 29349644
TI  - Does Statin Benefits Patients with Heart Failure Undergoing Percutaneous Coronary
      Intervention? Findings from the Melbourne Interventional Group Registry.
AB  - PURPOSE: The effectiveness of statins in improving clinical outcomes among
      patients with heart failure (HF) undergoing percutaneous coronary intervention
      (PCI) is unclear. We examined the association between use of statins and clinical
      outcomes in patients with HF included in the Melbourne Interventional Group
      registry. METHODS: Patients were followed from 30 days to 1 year post-PCI for a
      primary composite outcome of all-cause mortality and hospitalisation for
      cardiovascular (CV) causes. Secondary outcomes included major adverse cardiac
      events (MACE, a composite of all-cause mortality, myocardial infarction and
      target vessel revascularisation) and hospitalisation for CV causes. Outcomes were
      compared between statin-treated and non-statin-treated patients (at 30 days post
      PCI) using propensity scores to balance for risk factors. RESULTS: Among 991
      patients included in the inverse probability-weighted Cox model, statin use had
      no significant effect on the primary composite outcome [adjusted hazard ratio
      (aHR), 1.03; 95% confidence interval (CI), 0.68 to 1.56; p = 0.89], nor MACE
      (aHR, 0.99; 95% CI, 0.54 to 1.84; p = 0.99) or hospitalisation for CV causes (HR,
      1.13; 95% CI, 0.74 to 1.72; p = 0.57). CONCLUSIONS: Our results suggest that
      statin therapy may confer no significant benefits in patients with HF undergoing
      PCI. However, prospective randomised controlled trials are needed to provide more
      definitive answers.

PMID- 29349645
TI  - The Incidence and the Prognostic Impact of Acute Kidney Injury in Acute
      Myocardial Infarction Patients: Current Preventive Strategies.
AB  - Acute kidney injury (AKI) is one of the most common complications during
      hospitalization in various clinical settings. The goal of this review was to
      assess the incidence of AKI in acute myocardial infarction patients (AMI), how
      this incidence is affected by the diverse definitions, and if there is
      variability in the reported rates over recent years. Additionally, we sought to
      appraise the impact of AKI on short- and long-term prognosis of these patients.
      Finally, we report on the current preventive measures as they are suggested in
      the current guidelines of various societies, we comment on the evidence that
      support them, and we review the literature for other proposed therapeutic
      strategies, which either failed to prove their efficacy or they are not
      adequately confirmed yet. Due to the heterogeneity in AKI definition and in the
      population studied of the published data, the incidence of AKI ranged from 5.2 to
      59%. A recent meta-analysis reported a median value of 15.8%. All studies
      assessing AKI-related prognosis in AMI patients suggested that presence of AKI
      has detrimental effect on patients prognosis, raising mortality two- to threefold
      not only during the 30 first days but also during the first year after the acute
      event. Various treatment modalities have been proposed for prevention of AKI in
      AMI patients; however, the majority of them failed to prove their efficacy in the
      clinical trial arena. Hydration, use of iso- or low-osmolar agents at the lowest
      possible dose during coronary interventions, and use of statins have been
      proposed among others. Nonetheless, the prevalence of AKI after an AMI still
      remains high today and therefore it is crucial for the practicing physician to be
      aware of its presence and for the scientific community to identify novel measures
      for a more efficacious prevention.

PMID- 29349648
TI  - Establishment of a Monosomy 7 Leukemia Cell Line, MONO-7, With aras Gene
      Mutation.
AB  - A monosomy 7 leukemia cell line, designated MONO-7, was established from the
      peripheral blood of a patient with monosomy 7 acute myelocytic leukemia (French
      American-British classification M0). The cells were cultured continuously for
      more than 24 months in RPMI-1640 medium supplemented with 10% heat-inactivated
      fetal calf serum. The cell line exhibits an unclassified appearance.
      Cytochemically, alpha-naphthol-acetate esterase and myeloperoxidase are negative.
      Immunophenotypi-cally, the cell line expresses CD33, CD13, CD56, CD34, CD38, HLA
      DR, and CD45, but lacks T and B cell-associated antigens. Karyotypic analysis of
      the cell line showed only 45,XY,-7. Analysis of the N-ras gene mutation
      demonstrated identical mutations in fresh leukemic cells and the MONO-7 cell
      line. Clonal rearrangements of the immunoglobulin heavy-chain gene, T-cell
      receptor beta-chain gene, or T-cell receptor gamma-chain gene were not found in
      DNA extracted from MONO-7 cells. The growth of MONO-7 cells in vitro was
      stimulated by recombinant human granulocyte-macrophage colony-stimulating factor
      or interleukin 3. To our knowledge, this is the first report of the establishment
      of a cell line with the karyotype 45,XY,-7 with-out any other abnormality and
      with a ras gene mutation.

PMID- 29349647
TI  - Behaviour of freshwater snails (Radix balthica) exposed to the pharmaceutical
      sertraline under simulated predation risk.
AB  - Due to their potential for affecting the modulation of behaviour, effects of
      selective serotonin reuptake inhibitors (SSRIs) in the environment are
      particularly interesting regarding interspecies interactions and non-consumptive
      effects (NCEs) induced by predator cues in prey organisms. We evaluated the
      effects of sertraline (0.4, 40 ng/L, 40 ug/L) over 8 days on activity and habitat
      choice in the freshwater snail Radix balthica, on snails' boldness in response to
      mechanical stimulation (simulating predator attack), and their activity/habitat
      choice in response to chemical cues from predatory fish. We hypothesised that
      sertraline exposure would detrimentally impact NCEs elicited by predator cues,
      increasing predation risk. Although there were no effects of sertraline on NCEs,
      there were observed effects of chemical cue from predatory fish on snail
      behaviour independent of sertraline exposure. Snails reduced their activity in
      which the percentage of active snails decreased by almost 50% after exposure to
      fish cue. Additionally, snails changed their habitat use by moving away from open
      (exposed) areas. The general lack of effects of sertraline on snails' activity
      and other behaviours in this study is interesting considering that other SSRIs
      have been shown to induce changes in gastropod behaviour. This raises questions
      on the modes of action of various SSRIs in gastropods, as well as the potential
      for a trophic "mismatch" of effects between fish predators and snail prey in
      aquatic systems.

PMID- 29349649
TI  - Structure-activity relationships of flavanones, flavanone glycosides, and
      flavones in anti-degranulation activity in rat basophilic leukemia RBL-2H3 cells.
AB  - The incidence of type I allergies, which are associated with mast cell
      degranulation and local inflammation, is increasing, and new treatments are
      needed. To date, structure-activity relationships of flavonoids in their
      degranulation-inhibiting activity have not been systematically characterized. In
      the current study, the degranulation-inhibiting activity of a series of
      flavonoids was evaluated. The following three observations were made: (1) the
      activity disappears when a sugar moiety is introduced into the A ring of the
      flavanone; (2) the activity depends on the number of hydroxyl groups on the B
      ring; (3) the activity is markedly enhanced when a double bond is introduced into
      the C ring. The information obtained in the current study may guide the
      development of a therapy for type I allergies.

PMID- 29349652
TI  - Social Factors Associated with Non-initiation and Cessation of Predominant
      Breastfeeding in a Mother-Child Cohort in Spain.
AB  - Objective The aim of the study was to identify factors associated with non
      initiation and cessation of predominant breastfeeding (PBF) in a mother-child
      cohort from Spain. Materials and Methods The analysis included 2195 mother-infant
      from birth to 14 months post- delivery recruited between 2004 and 2008. Maternal
      characteristics were collected during the pregnancy. Lactation data were obtained
      at 6 and 14 months after delivery. PBF was defined as intake of breast milk plus
      liquids like juices or water. The PBF cessation was calculated using the date
      that women started PBF and the date that she reported to start giving infant
      formula and/or food. The relationship between maternal variables and PBF
      initiation and cessation was modeled using logistic and Cox proportional hazards
      regression analysis. Results The prevalence of PBF at hospital discharge was
      85.3, 53.4% at 3 months, 46.1% at 4 months and 7.2% at 6 month. Only two women
      continued PBF at 12 months and none at 14 months. The initiating of PBF was
      associated with higher levels of maternal education, being a first-time mother
      and worked in a non-manual occupation. Higher level of physical activity, not
      smoking and having a healthy BMI, were also positively associated with PBF
      initiation. PBF cessation was higher in young, obese women, who had had
      complications during the pregnancy, and who had lower levels of education and
      smoked. The employment status of women, in week 32 of pregnancy and also in month
      14 post-delivery, determined likelihood of PBF cessation. Conclusions Healthier
      habits and education positively influenced PBF initiation and duration. Decrease
      in PBF duration rates in Spain can be interpreted in part as a consequence of
      women returning to work.

PMID- 29349651
TI  - Epidemiology of Head Injuries Focusing on Concussions in Team Contact Sports: A
      Systematic Review.
AB  - BACKGROUND: Although injuries to the head represent a small proportion of all
      sport injuries, they are of great concern due to their potential long-term
      consequences, which are even suspected in mild traumatic brain injuries.
      OBJECTIVE: The aim of this review was to compare the incidence of concussions and
      other head injuries in elite level football, rugby, ice hockey and American
      Football. METHODS: Four electronic databases (CINAHL, PsycINFO, Web of Science,
      PubMed) were searched. Prospective cohort studies on the incidence of concussion
      in elite athletes aged 17 years or older that were published in an English
      language peer-reviewed journal since 2000 were included. Two authors
      independently evaluated study eligibility and quality. The extracted data on
      concussions were pooled in a meta-analysis using an inverse-variance fixed
      effects model. The extracted data on head injuries were reported in a narrative
      and tabular summary. RESULTS: The search yielded 7673 results of which 70
      articles were included in the qualitative and 47 in the quantitative analysis. In
      our meta-analysis, we found the highest concussion incidences in rugby match play
      (3.89 and 3.00 concussions per 1000 h and athletic exposures (AEs),
      respectively), and the lowest in men's football training (0.01 and 0.08 per 1000
      h and AEs, respectively). Overall, concussions and all head injuries were rare in
      training when compared to match play. Female players had an increased concussion
      risk in football and ice hockey when compared to male players. CONCLUSION: Future
      research should focus on concussion in women's contact sports, as there is little
      evidence available in this area. Methodological deficits are frequent in the
      current literature, especially regarding sample size and study power, and should
      be avoided.

PMID- 29349653
TI  - Exploring the Experiences of Middle Income Mothers in Practicing Exclusive
      Breastfeeding in Nairobi, Kenya.
AB  - Objectives To establish exclusive breastfeeding (EBF) practice, women are
      encouraged to initiate breastfeeding of their newborns within one hour of
      delivery and breastfeed exclusively for the first 6 months of the infant's life.
      Research in Kenya has shown evidence of a reduced rate of EBF with an increase in
      socio-economic class (SES). This study explores the experiences of middle-income
      women so as to understand their attitudes and practices of EBF and to contribute
      toward the Baby Friendly Hospital (BFHI) and Baby Friendly Community Initiatives
      (BFCI) programs in Kenya. Methods A qualitative study using nine in-depth
      interviews and two focus group discussions were conducted with middle-income
      women with a child < 2 years. Thematic content analysis was used to analyze the
      data. Results The majority of the women interviewed did not achieve EBF and this
      was attributed to many challenges that they encountered such as; inadequate
      workplace support including short maternity leave, lack of designated breast
      feeding facilities flexible hours and breastfeeding breaks. Support structures
      were highlighted as either inadequate or lacking while the internet was preferred
      by most of the women for breastfeeding information. Mass media was seen as more
      credible, though some women indicated that there was lack of depth in the
      information it provided. Conclusion The study showed that majority of women were
      unable to EBF for the first 6 months. Women experienced inadequate social,
      healthcare and workplace support and preferred online sites for information on
      breastfeeding than the healthcare professionals or mass media. Recommendation
      There is need to implement policies at the workplace that promote a breastfeeding
      friendly environment. There is also a need for more research on role of mass
      media in promotion of optimal breastfeeding practices, especially how to reach
      this population. There is a need for continued advocacy on social support
      including spousal, relatives, and other community members at the community level.

PMID- 29349654
TI  - The Role of Mentors in Early Intervention Referrals: Overlooked Views of
      Pediatric Residency Training Directors.
AB  - Objectives There continues to be a pressing need to increase referrals to family
      centered early intervention (EI) for more eligible infants and toddlers with
      inadequate consideration for the role of senior, mentoring professionals. Methods
      To address a dearth in our understanding, a subset of Pediatric Residency
      Training Directors shared views on EI, referral, and relevant training efforts.
      Results Participating directors primarily reported limited understanding of EI.
      Greater knowledge of family-focused EI correlated with its perceived helpfulness
      (r = .420; p = .021), which positively correlated with referring a child to EI.
      Despite 67% of the sample viewing pediatricians as 'most important' in screenings
      and EI referrals, residents were perceived as only somewhat aware of EI referral
      and services, and only somewhat aware of differences between clinic options and
      Part C EI. Although nearly all respondents noted minimal EI exposure during
      training, only 43% felt this amount was 'inadequate/insufficient'. The sample was
      fairly evenly divided in being 'extremely' or 'somewhat' interested in
      communicating with state EI leaders. Conclusions for Practice This preliminary
      analysis describes perceptions among senior medical professionals who may
      influence referrals via mentoring, training, and interdisciplinary collaboration.
      Findings inform next steps in terms of research, improving education for
      directors and residents, and collaborative information-sharing to bolster family
      centered EI referrals to improve child and family outcomes.

PMID- 29349655
TI  - Total body irradiation tremendously impair the proliferation, differentiation and
      chromosomal integrity of bone marrow-derived mesenchymal stromal stem cells.
AB  - Total body irradiation (TBI) is frequently used in hematopoietic stem cell
      transplantation (HSCT) and is associated with many complications due to radiation
      injury to the normal cells, including normal stem cells. Nevertheless, the
      effects of TBI on the mesenchymal stromal stem cell (MSC) are not fully
      understood. Bone marrow-derived MSCs (BM-MSCs) isolated from normal adults were
      irradiated with 200 cGy twice daily for consecutive 3 days, a regimen identical
      to that used in TBI-conditioning HSCT. The characteristics, differentiation
      potential, cytogenetics, hematopoiesis-supporting function, and carcinogenicity
      of the irradiated BM-MSCs were then compared to the non-irradiated control. The
      irradiated and non-irradiated MSCs shared similar morphology, phenotype, and
      hematopoiesis-supporting function. However, irradiated MSCs showed much lower
      proliferative and differentiative potential. Irradiation also induced clonal
      cytogenetic abnormalities of MSCs. Nevertheless, the carcinogenicity of
      irradiated MSCs is low in vitro and in vivo. In parallel with the ex vivo
      irradiation experiments, decreased proliferative and differentiative abilities
      and clonal cytogenetic abnormalities can also be found in MSCs isolated from
      transplant recipients who had received TBI-based conditioning previously. Thus,
      TBI used in HSCT drastically injury MSCs and may contribute to the development of
      some long-term complications associated with clonal cytogenetic abnormality and
      poor adipogenesis and osteogenesis after TBI.

PMID- 29349656
TI  - Correlations among multifocal electroretinography and optical coherence
      tomography findings in patients with Parkinson's disease.
AB  - To assess the correlation between functional and anatomical evaluations with
      multifocal electroretinography (mfERG) and spectral-domain optical coherence
      tomography (SD-OCT) in patients with Parkinson's disease (PD). This cross
      sectional study involved 116 eyes of 58 patients with PD and 30 age- and sex
      matched control subjects. All study participants underwent a comprehensive neuro
      ophthalmic examination, retinal single-layer thicknesses and volumes, and
      peripapillary retinal nerve fiber layer (pRNFL) measurements with SD-OCT, and the
      patients' mfERG recordings were evaluated. The macular retinal nerve fiber layer
      (mRNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), outer nuclear
      layer (ONL), retinal pigment epithelium (RPE), and photoreceptor layer (PR)
      thicknesses, and mRNFL, RPE, and PR volumes were found lower in PD compared to
      those of controls, while outer plexiform layer (OPL) volumes were increased (p <
      0.05). We found delayed implicit times and decreased amplitudes in the mfERG of
      PD patients versus those in control subjects (p < 0.05). We found significant
      correlations between outer macular volumes, PR thicknesses, and N1 amplitudes of
      rings 2 and 3and P1 amplitudes of rings 3, 4, and 5. Our study revealed thinning
      of both inner and outer retinal single layers, increased OPL volume, and delayed
      implicit times and decreased amplitudes in the mfERG of PD patients versus
      control subjects and correlation between structural and functional parameters.
      Our findings point out that SD-OCT and mfERG could both serve as non-invasive
      tools for evaluating ophthalmic manifestations of Parkinson's disease.

PMID- 29349657
TI  - Association between TBK1 mutations and risk of amyotrophic lateral
      sclerosis/frontotemporal dementia spectrum: a meta-analysis.
AB  - Recently, mutations in TBK1 (TANK-binding kinase 1) have been reported to be a
      cause of amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD)
      spectrum, but the relationship between them remains unclear owing to the small
      sample size and low mutation rate. Therefore, we performed a two-stage meta
      analysis to investigate the frequency of TBK1 mutations in ALS/FTD patients and
      the association between the mutations and risk of ALS/FTD spectrum. In the first
      stage, 12 studies involving 4173 ALS/FTD patients were included. The frequencies
      of loss of function (LoF) and missense mutations were 1.0% (95% CI 0.6-1.7%) and
      1.8% (95% CI 0.9-3.4%) in ALS/FTD patients respectively. Subgroup analysis
      suggested a higher prevalence of TBK1 mutations in European patients than that in
      Asian patients. In the second stage, 7 studies involving 3146 cases and 4856
      controls were enrolled. Results showed that TBK1 LoF mutations were associated
      with a significant increased risk for ALS/FTD spectrum (OR 11.78; 95% CI 4.21
      33.00; p < 0.0001), while TBK1 missense mutations were associated with a
      moderately increased susceptibility for ALS/FTD spectrum (OR 1.62; 95% CI 1.19
      2.19; p = 0.002). In conclusion, TBK1 LoF and missense mutations are not
      frequently found in ALS/FTD patients, and both of them are associated with an
      increased risk for ALS/FTD spectrum.

PMID- 29349658
TI  - The IL-10-producing regulatory B cells (B10 cells) and regulatory T cell subsets
      in neuromyelitis optica spectrum disorder.
AB  - B cells contribute to the pathogenesis of neuromyelitis optica (NMO) by producing
      Aquaporin 4-specific autoantibodies (AQP4-ab); on the other hand, there are
      certain B cells that suppress immune responses by producing regulatory cytokines,
      such as IL-10. In this study, we investigated the presence of IL-10-producing
      Breg cells among lymphocyte subsets. Twenty-two seropositive NMO spectrum
      disorder (NMOSD) patients (29 samples) and 13 healthy controls (HCs) (14 samples)
      were enrolled. All NMOSD patients have received one or more immunosuppressive
      drugs. The phenotype and frequency of B cell and T cell subsets in the peripheral
      blood were measured by flow cytometry. We defined Breg cells as IL-10-producing B
      (B10) cells, which are CD19+CD39+CD1d+IL-10+. The potential relations were
      evaluated between specific lymphocyte subsets and AQP4-ab intensity measured by
      the cell-based indirect immunofluorescence assay. The frequency of B10 cells was
      higher in patients with NMOSD regardless of the disease status than that in HCs
      (attack samples; p = 0.009 and remission samples; p < 0.001, respectively). In
      addition, the frequency of IL-17+ Treg cells among Treg cells was higher during
      remission than during an attack (uncorrected p = 0.032). Among the lymphocyte
      subsets, B10 cells alone showed a positive correlation with the intensity of AQP4
      ab positivity (rho [rho] = 0.402 and p = 0.031). It was suggested that the
      suppressive subsets including B10 and IL-17+ Treg cells might have important
      roles in controlling disease status in NMOSD. Further functional studies may help
      to elucidate the immunological role of B10 and IL-17+ Treg cells in NMOSD.

PMID- 29349659
TI  - [Self- and informant-rating mood scales applied in elderly persons with
      Alzheimer's dementia, with or without a language disorder].
AB  - INTRODUCTION: Alzheimer's Dementia (AD) may be associated with symptoms of
      depression. In AD, problems of language expression or understanding will arise
      sooner or later. The aim of this study was to determine whether elderly persons
      with AD, with or without a language disorder, experience difficulties
      understanding and answering mood related questions. In addition to this, it was
      our object to test the validity of the answers of nurses as informants, on the
      mood of an elderly client. METHODS: 53 elderly persons, living in care homes, and
      their nurses, took part in the study. 25 participants had been diagnosed with
      Alzheimer's disease, 28 participants had no cognitive impairment. Language skills
      were tested using the SAN-test (Stichting Afasie Nederland) and subtests of the
      Aachen Aphasia Test (AAT). Mood was assessed with the Beck Depression Inventory
      second edition (BDI-II-NL) and the Geriatric Depression Scale (GDS-30). RESULTS:
      There were no significant differences in scores on the mood related
      questionnaires between participants without cognitive impairment and participants
      with Alzheimer's disease, with or without a language disorder. The correlation
      between self- and informant-rating was very limited. In general, nurses reported
      more depressive symptoms than the elderly persons did themselves. Disparities
      between self- and informant-ratings varied from informant scores overestimating
      low self-ratings of depression to informant scores underestimating high self
      ratings. CONCLUSION: Alzheimer's disease, whether or not it is complicated by a
      language disorder, does not disturb the normal score distribution on either test
      (BDI or GDS). This means that elderly persons with Alzheimer's disease are
      capable of adequately answering questions related to their own mood. However,
      considerable discrepancies were found between observer- and self-ratings of
      emotional wellbeing. Therefore it is important to not only take into account the
      information of an informant when testing for depression, but also the elderly
      person's own assessment of their mood.

PMID- 29349660
TI  - Progestogen Hypersensitivity.
AB  - PURPOSE OF REVIEW: Progestogen hypersensitivity (PH) is a rare disorder which
      usually occurs in women of childbearing age with symptoms ranging from urticaria
      with or without angioedema, multiple organ involvement consistent with allergic
      anaphylaxis, to a spectrum of other non-evanescent skin eruptions. In this
      review, we present a clinical vignette of PH and discuss the clinical
      presentation and proposed pathomechanisms, diagnosis, and treatment of PH. RECENT
      FINDINGS: The hypersensitivity symptoms are associated with exogenous progestin
      exposure (e.g., contraceptive medicines, in vitro fertilization therapy) or
      endogenous progesterone from progesterone surges during the luteal phase of the
      menstrual cycle and pregnancy. Recognition of this condition can be challenging
      to the clinician due to its heterogeneous clinical presentation. It has been
      recently proposed to use the new term "progestogen hypersensitivity" to replace
      "autoimmune progesterone dermatitis" due to the lack of evidence supporting an
      autoimmune mechanism for this disorder. In addition, diagnostic and treatment
      algorithms are now available that can lead to successful management of this
      condition. More new developments of Progesterone desensitization protocols are
      now available which appear to be the safest and most effective long-term
      treatment option for PH. With the extensive use of oral contraceptives and
      increased use of supra-physiologic doses of progesterone to support pregnancy in
      in vitro fertilization, there is likely to be a higher prevalence of PH in the
      future than currently recognized. Therefore, the allergist-immunologist will be
      required to collaborate with gynecologists and reproductive endocrinologists to
      diagnose and treat this condition.

PMID- 29349661
TI  - PKM2 is involved in neuropathic pain by regulating ERK and STAT3 activation in
      rat spinal cord.
AB  - BACKGROUND: Pyruvate kinase isozymes M2 (PKM2), as a member of pyruvate kinase
      family, plays a role of glycolytic enzyme in glucose metabolism. It also
      functions as protein kinase in cell proliferation, signaling, immunity, and gene
      transcription. In this study, the role of PKM2 in neuropathic pain induced by
      chronic constriction injury (CCI) was investigated. METHODS: Rats were randomly
      grouped to establish CCI models. PKM2, extracellular regulated protein kinases
      (EKR), p-ERK, signal transducers and activators of transcription (STAT3), p
      STAT3, phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) and p-PI3K/AKT
      proteins expression in spinal cord was examined by Western blot analysis.
      Cellular location of PKM2 was examined by immunofluorescence. Knockdown of PKM2
      was achieved by intrathecal injection of specific small interfering RNA (siRNA).
      Von Frey filaments and radiant heat tests were performed to determine mechanical
      allodynia and thermal hyperalgesia respectively. Lactate and adenosine
      triphosphate (ATP) contents were measured by specific kits. Tumor necrosis factor
      alpha (TNF-alpha) and interleukin-1 beta (IL-1beta) levels were detected by ELISA
      kits. RESULTS: CCI markedly increased PKM2 level in rat spinal cord. Double
      immunofluorescent staining showed that PKM2 co-localized with neuron, astrocyte,
      and microglia. Intrathecal injection of PKM2 siRNA not only attenuated CCI
      induced ERK and STAT3 activation, but also attenuated mechanical allodynia and
      thermal hyperalgesia induced by CCI. However, PKM2 siRNA failed to inhibit the
      activation of AKT. In addition, PKM2 siRNA significantly suppressed the
      production of lactate and pro-inflammatory mediators. CONCLUSION: Our findings
      demonstrate that inhibiting PKM2 expression effectively attenuates CCI-induced
      neuropathic pain and inflammatory responses in rats, possibly through regulating
      ERK and STAT3 signaling pathway.

PMID- 29349663
TI  - Ibandronate metal complexes: solution behavior and antiparasitic activity.
AB  - To face the high costs of developing new drugs, researchers in both industry and
      academy are looking for ways to repurpose old drugs for new uses. In this sense,
      bisphosphonates that are clinically used for bone diseases have been studied as
      agents against Trypanosoma cruzi, causative parasite of Chagas disease. In this
      work, the development of first row transition metal complexes (M = Co2+, Mn2+,
      Ni2+) with the bisphosphonate ibandronate (iba, H4iba representing the neutral
      form) is presented. The in-solution behavior of the systems containing iba and
      the selected 3d metal ions was studied by potentiometry. Mononuclear complexes
      [M(Hxiba)](2-x)- (x = 0-3) and [M(Hiba)2]4- together with the formation of the
      neutral polynuclear species [M2iba] and [M3(Hiba)2] were detected for all studied
      systems. In the solid state, complexes of the formula [M3(Hiba)2(H2O)4].6H2O were
      obtained and characterized. All obtained complexes, forming [M(Hiba)]- species
      under the conditions of the biological studies, were more active against the
      amastigote form of T. cruzi than the free iba, showing no toxicity in mammalian
      Vero cells. In addition, the same complexes were selective inhibitors of the
      parasitic farnesyl diphosphate synthase (FPPS) enzyme showing poor inhibition of
      the human one. However, the increase of the anti-T. cruzi activity upon
      coordination could not be explained neither through the inhibition of TcFPPS nor
      through the inhibition of TcSPPS (T. cruzi solanesyl-diphosphate synthase). The
      ability of the obtained metal complexes of catalyzing the generation of free
      radical species in the parasite could explain the observed anti-T. cruzi
      activity.

PMID- 29349664
TI  - Sparse Functional Identification of Complex Cells from Spike Times and the
      Decoding of Visual Stimuli.
AB  - We investigate the sparse functional identification of complex cells and the
      decoding of spatio-temporal visual stimuli encoded by an ensemble of complex
      cells. The reconstruction algorithm is formulated as a rank minimization problem
      that significantly reduces the number of sampling measurements (spikes) required
      for decoding. We also establish the duality between sparse decoding and
      functional identification and provide algorithms for identification of low-rank
      dendritic stimulus processors. The duality enables us to efficiently evaluate our
      functional identification algorithms by reconstructing novel stimuli in the input
      space. Finally, we demonstrate that our identification algorithms substantially
      outperform the generalized quadratic model, the nonlinear input model, and the
      widely used spike-triggered covariance algorithm.

PMID- 29349662
TI  - Roles and maturation of iron-sulfur proteins in plastids.
AB  - One reason why iron is an essential element for most organisms is its presence in
      prosthetic groups such as hemes or iron-sulfur (Fe-S) clusters, which are notably
      required for electron transfer reactions. As an organelle with an intense
      metabolism in plants, chloroplast relies on many Fe-S proteins. This includes
      those present in the electron transfer chain which will be, in fact, essential
      for most other metabolic processes occurring in chloroplasts, e.g., carbon
      fixation, nitrogen and sulfur assimilation, pigment, amino acid, and vitamin
      biosynthetic pathways to cite only a few examples. The maturation of these Fe-S
      proteins requires a complex and specific machinery named SUF (sulfur
      mobilisation). The assembly process can be split in two major steps, (1) the de
      novo assembly on scaffold proteins which requires ATP, iron and sulfur atoms,
      electrons, and thus the concerted action of several proteins forming early acting
      assembly complexes, and (2) the transfer of the preformed Fe-S cluster to client
      proteins using a set of late-acting maturation factors. Similar machineries,
      having in common these basic principles, are present in the cytosol and in
      mitochondria. This review focuses on the currently known molecular details
      concerning the assembly and roles of Fe-S proteins in plastids.

PMID- 29349665
TI  - Following the correction of varus deformity of the knee through total knee
      arthroplasty, significant compensatory changes occur not only at the ankle and
      subtalar joint, but also at the foot.
AB  - PURPOSE: This study aimed to assess radiological changes of the ankle joint,
      subtalar joint and foot following the correction of varus deformity of the knee
      with total knee arthroplasty (TKA). It was hypothesized that following the
      correction of varus deformity by TKA, compensatory reactions would occur at the
      subtalar joint in accordance with the extent of the correction. METHODS: For this
      prospective study, 375 knees of patients who underwent TKA between 2011 and 2012
      were enrolled. The varus angle of the knee, talar tilt of the ankle joint (TT),
      ground-talar dome angle of the foot (GD), anterior surface angle of the distal
      tibia and lateral surface angle of the distal tibia, heel alignment ratio (HR),
      heel alignment angle (HA), and heel alignment distance (HD) were measured on
      radiographs obtained pre-operatively and at post-operative 6 months. RESULTS: The
      mean correction angle in varus deformity of the knee was 10.8 +/- 4.1 degrees .
      TT and GD changed significantly from 0.4 +/- 1.9 degrees  and 6.5 +/- 3.1 degrees
      pre-operatively to 0.1 +/- 1.8 degrees  and 0.2 +/- 2.1 degrees , respectively
      (p = 0.007, p < 0.001). No correlation was found between the preop-postop
      variance in mechanical axis of the lower extremity (MA) and TT, but there was a
      strong correlation between the preop-postop variance in MA and GD (r = 0.701).
      HR, HA and HD also changed significantly post-operatively, and the preop-postop
      variance in MA showed correlations with the preop-postop variances in HR, HA and
      HD (r = 0.206, - 0.348, and - 0.418). TT and the three indicators of hindfoot
      alignment all shifted to varus whereas GD was oriented in valgus. CONCLUSION:
      Following the correction of varus deformity of the knee through TKA, significant
      compensatory changes occurred not only at the ankle and subtalar joints, but also
      at the foot. The findings of this study are useful in predicting the orientation
      of changes in the ankle and subtalar joints and the foot following TKA, and in
      determining the sequence of surgery when both the ankle and knee have a problem.
      In other words, changes in the parts of the lower extremity below the ankle joint
      following the correction of varus deformity of the knee must be considered when
      TKA is planned and performed. Patients who have problems at the ankle, subtalar,
      and foot joints in addition to varus deformity of the knee are recommended to
      undergo knee joint correction first. LEVEL OF EVIDENCE: II.

PMID- 29349666
TI  - New Frontiers in Cancer Therapy: Monoclonal Antibody Therapy of Hematologic
      Malignancies.

PMID- 29349667
TI  - Comparison of Enalapril, Candesartan and Intralesional Triamcinolone in Reducing
      Hypertrophic Scar Development: An Experimental Study.
AB  - BACKGROUND: The purpose of this study was to compare the effects of oral
      enalapril, an angiotensin-converting enzyme inhibitor (ACE-I), oral candesartan,
      an angiotensin receptor blocker (ARB), and intralesional corticosteroid
      treatments in reducing scar formation. METHODS: Twenty male rabbits were divided
      into five study groups: A (sham), B (control), C (ACE-I), D (ARB) and E
      (intralesional corticosteroid). The rabbit ear hypertrophic scar model was used.
      The hypertrophic scars were photographed and analyzed with the program ImageJ
      quantitatively to determine the degree of collagen fibers. The scar elevation
      index (SEI) was calculated at the end of the 40th day. Tissue samples were
      stained with hematoxylin and eosin and Masson's trichrome and examined under
      light microscopy for the determination of fibroblast number, epithelization,
      vascularization, inflammation and fibrosis. RESULTS: The SEI was the highest in
      the control group with the highest number of fibroblasts under the epithelium. In
      the steroid group, the SEI was significantly lower than both the ACE-I (p: 0.02)
      and ARB (p: 0.001) groups. The density of type 1 collagen fibers was the lowest
      in the control group, whereas type 3 collagen fibers were highest in that group.
      The ACE-I and ARB groups were similar regarding densities of type 1 and type 3
      collagen fibers. The density of type 1 collagen fibers was the highest in the
      steroid group, whereas the density of type 3 collagen fibers was the lowest in
      that group. CONCLUSIONS: Enalapril, candesartan and intralesional steroid
      therapies were all effective in reducing scar tissue development; however,
      enalapril and steroid groups revealed better results. NO LEVEL ASSIGNED: 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- 29349668
TI  - Serum MMP-9 Diagnostics, Prognostics, and Activation in Acute Coronary Syndrome
      and Its Recurrence.
AB  - Matrix metalloproteinase (MMP)-9 is crucial in atherosclerotic plaque rupture and
      tissue remodeling after a cardiac event. The balance between MMP-9 and endogenous
      inhibitor, tissue inhibitors of matrix metalloproteinase 1 (TIMP-1), is important
      in acute coronary syndrome (ACS). This is an age- and gender-matched case-control
      study of ACS (N = 669). Patients (45.7%) were resampled after recovery, and all
      were followed up for 6 years. The molecular forms of MMP-9 were investigated by
      gelatin zymography. Diagnostically, MMP-9 and the MMP-9/TIMP-1 molar ratio were
      associated with ACS (OR 5.81, 95% CI 2.65-12.76, and 4.96, 2.37-10.38). The MMP-9
      concentrations decreased 49% during recovery (p < 0.001). The largest decrease of
      these biomarkers between acute and recovery phase (DeltaMMP-9) protected the
      patients from major adverse cardiac events, especially the non-fatal events. The
      fatal events were associated with in vitro activatable MMP-9 levels (p = 0.028).
      Serum MMP-9 and the MMP-9/TIMP-1 molar ratio may be valuable in ACS diagnosis and
      prognosis. High serum MMP-9 activation potential is associated with poor
      cardiovascular outcome.

PMID- 29349669
TI  - Positive Correlation between Matrix Metalloproteinases and Epithelial-to
      Mesenchymal Transition and its Association with Clinical Outcome in Bladder
      Cancer Patients.
AB  - Involvement of matrix metalloproteinases (MMPs) in the pathogenesis of urothelial
      carcinoma elects them to be sensitive marker for clinical and prognostic
      implications. MMPs regulate tumor growth and invasion by inducing epithelial-to
      mesenchymal transition (EMT) which is characterized by the complex reprogramming
      of epithelial cells and ultimately bring about major changes in the structural
      organization of bladder urothelium. The present study has been undertaken to
      evaluate the clinical relevance of MMPs in two distinct types of bladder cancer
      disease. Expression analysis of MMPs namely MMP-2, MMP-7, MMP-9 and EMT markers
      including epithelial marker, E-cadherin; mesenchymal markers, N-cadherin and
      Vimentin; and EMT-activating transcriptional factors (EMT-ATFs), Snail, Slug,
      Twist and Zeb was done in 64 cases of bladder tumor tissues [{Non-muscle invasive
      bladder cancer (NMIBC): 35 cases} and {Muscle invasive bladder cancer (MIBC): 29
      cases}] by real-time quantitative polymerase chain reaction (RT-qPCR).
      Immunohistochemistry (IHC) staining was done in matched bladder tumor tissues to
      evaluate the protein expression and localization of E-cadherin, N-cadherin,
      Vimentin, Snail, and Slug. Our data showed overexpression of MMP-2, MMP-7 and MMP
      9 at transcriptome level in 32.8%, 25% and 37.5% bladder tumor cases
      respectively. These tumor tissues were examined for higher expression of
      mesenchymal markers (N-cadherin and Vimentin) at mRNA and protein level and
      exhibited statistical association with tumor stage and tumor grade (p = 0.02, p =
      0.04, Mann-Whitney test). Significant statistical correlation in tumor tissues
      with overexpressed MMPs has also been observed between gain of transcriptional
      factors and weak expression of E-cadherin with tumor stage, grade, gender,
      presence of hematuria and smoking history of the patients. Gene expression
      patterns of EMT markers in bladder tumors with overexpressed MMPs and their
      significant association with clinical profile validate the important role of MMPs
      in the pathogenesis of urothelial carcinoma of bladder (UCB). Increased
      expression of specific MMPs may affect several downstream EMT programs and thus
      may improve its diagnostic and prognostic utility in clinical setting.

PMID- 29349670
TI  - Working (longer than) 9 to 5: are there cardiometabolic health risks for young
      Australian workers who report longer than 38-h working weeks?
AB  - PURPOSE: The average Australian working week in middle-aged and older workers
      exceeds government recommendations. Long working weeks are associated with poor
      health outcomes; however, the relationship between long working weeks and health
      in young Australian workers is unknown. METHODS: Data were drawn from the 22-year
      follow-up of the Western Australian Pregnancy Cohort (Raine) Study in Perth,
      Western Australia. Information was available from 873 young adults about working
      hours per week, shift work and sleep duration. Blood samples provided measures of
      cardiometabolic risk (CMR) factors. RESULTS: Almost one-third (32.8%) of young
      workers reported > 38 h working weeks. This was commonly reported in mining and
      construction industries for males; health and social assistance, mining and
      retail trade industries for females. CMR factors including increased waist
      circumference, higher fasting plasma glucose and reduced HDL cholesterol were
      associated with > 38 h working weeks. These relationships were not moderated by
      gender or by BMI for glucose and HDL cholesterol. Total sleep time was
      significantly lower in both male and female workers reporting > 38 h working
      weeks, but did not mediate the relationships seen with CMR factors. CONCLUSIONS:
      These findings point to early associations between > 38 h working weeks and CMR
      risk, and highlight the potential benefit of making young employees aware of the
      health associations with working arrangements to reduce the longer-term
      relationships seen with working hours and poor cardiometabolic health in
      population studies.

PMID- 29349671
TI  - Is Older Age Associated with Higher Self- and Other-Rated ASD Characteristics?
AB  - Autism spectrum disorder (ASD) characteristics seem to abate over time, but
      whether this protracts until late adulthood is largely unknown. We cross
      sectionally investigated self- and other-reported ASD characteristics of adults
      with (ASD: Nmax-self = 237, Nmax-other = 130) and without ASD (COM: Nmax-self =
      198, Nmax-other = 148) aged 19-79 years. Within the ASD group, self-reported ASD
      characteristics, and sensory sensitivities were highest in middle adulthood,
      while age was not associated to empathy. Sex differences were also found.
      However, age-and sex-related differences were not revealed by others and self-
      and other-report were poorly concordant. These results show that ASD
      characteristics in adulthood are differently perceived across age, sex, and
      informants and suggest that it is important to repeatedly assess self-reported
      ASD characteristics during adulthood.

PMID- 29349672
TI  - STA-ACA bypass using the ipsilateral free STA graft as an interposition graft and
      A3-A3 anastomosis for treatment of bilateral ACA steno-occlusive ischemia.
AB  - BACKGROUND: Anterior cerebral artery (ACA)-related ischemia is a rare entity in
      patients with atherosclerosis. Some surgical treatments are reported to date.
      METHOD: We present the modification of intracranial-intracranial and intracranial
      extracranial bypasses for symptomatic bilateral ACA steno-occlusive disease. The
      A3-A3 bypass followed by the superficial temporal artery-ACA bypass using the
      ipsilateral free superficial temporal artery graft is useful without harvesting
      of the radial artery. CONCLUSION: Bilateral ACA steno-occlusive induced ischemia
      can be treated with tailored bypass procedures.

PMID- 29349673
TI  - Pharmacological dissection of the cellular mechanisms associated to the
      spontaneous and the mechanically stimulated ATP release by mesentery endothelial
      cells: roles of thrombin and TRPV.
AB  - Endothelial cells participate in extracellular ATP release elicited by
      mechanosensors. To characterize the dynamic interactions between mechanical and
      chemical factors that modulate ATP secretion by the endothelium, we assessed and
      compared the mechanisms participating in the spontaneous (basal) and mechanically
      stimulated secretion using primary cultures of rat mesentery endothelial cells.
      ATP/metabolites were determined in the cell media prior to (basal) and after cell
      media displacement or a picospritzer buffer puff used as mechanical stimuli.
      Mechanical stimulation increased extracellular ATP that peaked within 1 min, and
      decayed to basal values in 10 min. Interruption of the vesicular transport route
      consistently blocked the spontaneous ATP secretion. Cells maintained in media
      lacking external Ca2+ elicited a spontaneous rise of extracellular ATP and
      adenosine, but failed to elicit a further extracellular ATP secretion following
      mechanical stimulation. 2-APB, a TRPV agonist, increased the spontaneous ATP
      secretion, but reduced the mechanical stimulation-induced nucleotide release.
      Pannexin1 or connexin blockers and gadolinium, a Piezo1 blocker, reduced the
      mechanically induced ATP release without altering spontaneous nucleotide levels.
      Moreover, thrombin or related agonists increased extracellular ATP secretion
      elicited by mechanical stimulation, without modifying spontaneous release. In
      sum, present results allow inferring that the spontaneous, extracellular
      nucleotide secretion is essentially mediated by ATP containing vesicles, while
      the mechanically induced secretion occurs essentially by connexin or pannexin1
      hemichannel ATP transport, a finding fully supported by results from Panx1-/-
      rodents. Only the latter component is modulated by thrombin and related receptor
      agonists, highlighting a novel endothelium-smooth muscle signaling role of this
      anticoagulant.

PMID- 29349675
TI  - Saphenous vein graft percutaneous coronary intervention : A different kind of
      animal.

PMID- 29349674
TI  - Extracorporeal life support in cardiogenic shock: indications and management in
      current practice.
AB  - Veno-arterial extracorporeal life support (VA-ECLS) provides circulatory and
      respiratory stabilisation in patients with severe refractory cardiogenic shock.
      Although randomised controlled trials are lacking, the use of VA-ECLS is
      increasing and observational studies repeatedly have shown treatment benefits in
      well-selected patients. Current clinical challenges in VA-ECLS relate to optimal
      management of the individual patient on extracorporeal support given its inherent
      complexity. In this review article we will discuss indications, daily clinical
      management and complications of VA-ECLS in cardiogenic shock refractory to
      conventional treatment strategies.

PMID- 29349676
TI  - Environment-Friendly Synthesis of Trace Element Zn, Sr, and F Codoping
      Hydroxyapatite with Non-cytotoxicity and Improved Osteoblast Proliferation and
      Differentiation.
AB  - Hydroxyapatite (HAp, Ca10[PO4]6[OH]2) doped with numerous trace elements
      possesses sensational biochemical effects in natural bones. To study the
      biochemical function of Zn, Sr, and F elements, a series of neoteric HAp
      biomaterials with Zn, Sr, and F concentrations close to natural bones are firstly
      synthesized by one-pot hydrothermal method. These materials are characterized
      through powder X-ray diffraction (XRD), Fourier transform infrared spectroscopy
      (FTIR), and scanning electron microscope (SEM). All the synthesized materials are
      HAp phase. The morphology of these materials is nanorods. The phenomenon that
      L929 cells can live even at 400 MUg/mL powder concentration indicates that these
      materials are non-cytotoxic. The active effects of samples on proliferation and
      differentiation of osteoblast cells (MC3T3-E1) are certified by MTT and alkaline
      phosphatase (ALP) activity assays. The adhesion and proliferation of osteoblast
      measurement manifest that amounts of MC3T3-E1 advances about 1.86 times for
      ZnSrF/HAp compared with undoped HAp. This achievement may inspire us on the
      artificial design of new-style bionic bone grafts using trace bioactive elements
      and also suggest its latent applications in orthopedic surgery and bone
      osseointegration.

PMID- 29349678
TI  - Hughes Syndrome: Antiphospholipid Syndrome.

PMID- 29349677
TI  - Mercuric Chloride Induced Ovarian Oxidative Stress by Suppressing Nrf2-Keap1
      Signal Pathway and its Downstream Genes in Laying Hens.
AB  - The present study evaluated the effects of mercury chloride (HgCl2) on follicular
      atresia rate, sex hormone secretion, and ovarian oxidative stress in laying hens.
      Antioxidant enzyme genes and the nuclear factor erythroid 2-related factor 2
      (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) signal pathway were further
      studied to uncover the molecular mechanism. A total of 768 40-week-old Hy-Line
      Brown laying hens were randomly allocated to four treatments with eight pens per
      treatment and 24 hens of each pen. The birds were fed with four experimental
      diets containing graded levels of mercury (Hg) at 0.280, 3.325, 9.415, and 27.240
      mg/kg, respectively. Results revealed that a positive relationship occurred
      between the accumulation of Hg in ovary and follicular atresia rate. Progesterone
      (P4) level significantly decreased in all Hg-treatment groups (P < 0.05), and
      follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were the
      lowest in the 27.240-mg/kg Hg group. Besides, the activities of catalase (CAT),
      superoxidative dismutase (SOD), glutathione reductase (GR), and glutathione (GSH)
      content were significantly decreased in all Hg-treatment groups (P < 0.05).
      Glutathione peroxidase (GSH-Px) activity significantly decreased, while
      malondialdehyde (MDA) content sharply increased in the 27.240-mg/kg Hg group (P <
      0.05). In addition, there were positive relationships between antioxidant enzyme
      activities and antioxidant gene expressions or between antioxidant gene
      expressions and Nrf2 mRNA expression, while negative correlations occurred
      between Nrf2 and Keap1 at transcription and protein levels. It could be concluded
      that Hg induced ovarian function disorders and ovarian oxidative stress by means
      of impairing the Nrf2-Keap1 signal pathway in laying hens.

PMID- 29349679
TI  - Autoimmune encephalitis associated with glutamic acid decarboxylase antibodies: a
      case series.
AB  - Antibodies against glutamic acid decarboxylase (GAD) are associated with various
      neurologic conditions described in patients including stiff person syndrome,
      cerebellar ataxia, refractory epilepsy, limbic and extralimbic encephalitis. GAD
      antibodies-related limbic encephalitis cases are well described; reports of
      extralimbic involvement are limited. We describe four cases of GAD antibody
      related autoimmune encephalitis. Three of them had extralimbic involvement and
      only one had limbic encephalitis.

PMID- 29349680
TI  - Ultrasound evaluation of the airway in the ED: a feasibility study.
AB  - BACKGROUND: Recognition of the difficult airway is a critical element of
      emergency practice. Mallampati score and body mass index (BMI) are not always
      predictive and they may be unavailable in critically ill patients.
      Ultrasonography provides high-resolution images that are rapidly obtainable,
      mobile, and non-invasive. Studies have shown correlation of ultrasound
      measurements with difficult laryngoscopy; however, none have been performed in
      the Emergency Department (ED) using a consistent scanning protocol. OBJECTIVES:
      This study seeks to determine the feasibility of ultrasound measurements of the
      upper airway performed in the ED by emergency physicians, the inter-rater
      reliability of such measurements, and their relationship with Mallampati score
      and BMI. METHODS: A convenience sample of volunteer ED patients and healthy
      volunteers with no known airway issues, aged > 18 years, had images taken of
      their airway using a standardized ultrasound scanning protocol by two EM
      ultrasound fellowship trained physicians. Measurements consisted of tongue base,
      tongue base-to-skin, epiglottic width and thickness, and pre-epiglottic space.
      Mean and standard deviation (SD) were used to summarize measurements. Inter-rater
      reliability was assessed by intraclass correlation coefficients (ICCs). Analysis
      of variance with linear contrasts was used to compare measurements with
      Mallampati scores and linear regression with BMI. RESULTS: Of 39 participants,
      50% were female, 50% white, 42% black, with median age 32.5 years (range 19-90),
      and BMI 26.0 (range 19-47). Mean +/- SD for each measurement (mm) was as follows:
      tongue base (44.6 +/- 5.1), tongue base-to-skin (60.9 +/- 5.3), epiglottic width
      (15.0 +/- 2.8) and thickness (2.0 +/- 0.37), and pre-epiglottic space (11.4 +/-
      2.4). ICCs ranged from 0.76 to 0.88 for all measurements except epiglottis
      thickness (ICC = 0.57). Tongue base and tongue base-to-skin thickness were found
      to increase with increasing Mallampati score (p = .04, .01), whereas only tongue
      to-skin thickness was loosely correlated with BMI (r = .38). CONCLUSIONS: A
      standardized ultrasound scanning protocol demonstrates that the airway can be
      measured by emergency sonologists with good inter-operator reliability in all but
      epiglottic thickness. The measurements correlate with Mallampati score but not
      with BMI. Future investigation might focus on ultrasound evaluation of the airway
      in patients receiving airway management to determine whether ultrasound can
      predict challenging or abnormal airway anatomy prior to laryngoscopy.

PMID- 29349681
TI  - Erratum to: Functional Analysis of Membrane Proteins Produced by Cell-Free
      Translation.

PMID- 29349682
TI  - Managing Obesity in Primary Care: Breaking Down the Barriers.
AB  - : Several Australian obesity management guidelines have been developed for
      general practice but, to date, implementation of these guidelines has been shown
      to be inadequate. In this review, we explore the barriers to obesity treatment
      and propose a four-stage plan to manage individuals with obesity in general
      practice using a framework of a multidisciplinary team. FUNDING: Novo Nordisk.

PMID- 29349683
TI  - Plantamajoside Inhibits Lipopolysaccharide-Induced MUC5AC Expression and
      Inflammation through Suppressing the PI3K/Akt and NF-kappaB Signaling Pathways in
      Human Airway Epithelial Cells.
AB  - It has been reported that plantamajoside (PMS), a major natural compound isolated
      from Plantago asiatica, has anti-inflammatory activities. However, the effect of
      PMS on respiratory inflammatory diseases has not yet been studied. The present
      study aimed to evaluate the effect of PMS on lipopolysaccharide (LPS)-induced
      airway inflammation and the underlying mechanism. The results showed that PMS did
      not affect the cell viability of 16-HBE cells. PMS (20 and 40 MUg/ml) decreased
      the expression levels of MUC5AC, IL-6, and IL-1beta, which were induced by LPS
      treatment. PMS inhibited the LPS-induced phosphorylation of Akt and p65. In
      addition, inhibitors of the PI3K/Akt and NF-kappaB pathways attenuated the effect
      of LPS on 16-HBE cells. In conclusion, PMS inhibits LPS-induced MUC5AC expression
      and inflammation through suppressing the PI3K/Akt and NF-kappaB signaling
      pathways, indicating that PMS may be a potential therapy for the treatment of
      respiratory inflammatory diseases.

PMID- 29349684
TI  - Fcgamma Receptor Signaling in Phagocytes.
AB  - Fcgamma receptors are among the best-studied phagocytic receptors. The key
      features of Fcgamma receptor-mediated phagocytosis include phagocytic cup
      formation by extensive actin cytoskeletal rearrangements, particle engulfment,
      and the release of proinflammatory mediators such as cytokines and reactive
      oxygen species. These events are elegantly regulated by the simultaneous
      engagement of activating and inhibitory Fcgamma receptors and by intracellular
      signaling molecules. Extensive studies in the past several years have defined the
      molecular mechanisms of the phagocytic process. The purpose of this review is to
      revisit some of the well-established signaling pathways as well as to summarize
      the new findings in this field.

PMID- 29349686
TI  - Two-year results after coronary stenting of small vessels in Japanese population
      using 2.25-mm diameter sirolimus-eluting stent with bioresorbable polymer:
      primary and long-term outcomes of CENTURY JSV study.
AB  - : Percutaneous coronary intervention (PCI) in coronary artery disease (CAD) with
      very small vessels remains challenging. The aim of this study is to evaluate the
      safety and effectiveness of the 2.25-mm diameter Ultimaster sirolimus-eluting
      stent in the treatment of Japanese patients with CAD due to lesions in very small
      vessels. The CENTURY JSV study is a prospective, multicentre, single-arm study.
      Seventy patients with lesions deemed suitable for implantation of a 2.25-mm
      diameter stent were enrolled at seven hospitals in Japan. Patients underwent
      clinical follow-up at 1-, 9-month, 1-, and 2-year after the PCI procedure. The
      primary endpoint was the major adverse cardiac event (MACE), a composite of
      cardiac death, target vessel myocardial infarction (MI), and clinically driven
      target lesion revascularization (TLR) free rate at 9-month following the
      procedure. The MACE-free rate was 97.1%, and the lower limit of the two-sided 95%
      confidence interval (CI) was 90.1%, which exceeded the threshold of 80% set as
      the performance goal. Angiographic in-stent and in-segment late loss at 9-month
      were 0.22 +/- 0.31 and - 0.02 +/- 0.34 mm, respectively. Between 9 months and 2
      years, two additional TLRs occurred. Stent thrombosis, bleeding and vascular
      complication did not occur throughout 2 years. The 2.25-mm diameter Ultimaster(r)
      bioresorbable-polymer sirolimus-eluting stent is safe and effective for treating
      lesions in very small coronary arteries throughout 2 years after stent
      implantation. CLINICAL TRIAL REGISTRATION: UMIN000012928.

PMID- 29349685
TI  - Solute Transport in the Bone Lacunar-Canalicular System (LCS).
AB  - PURPOSE OF REVIEW: Solute transport in the lacunar-canalicular system (LCS) plays
      important roles in osteocyte metabolism and cell-cell signaling. This review will
      summarize recent studies that establish pericellular matrix (PCM), discovered
      inside the LCS, as a crucial regulator of solute transport in bone. RECENT
      FINDINGS: Utilizing confocal imaging and mathematical modeling, recent studies
      successfully quantified molecular diffusion and convection in the LCS as well as
      the size-dependent sieving effects of the PCM, leading to the quantification of
      the effective PCM fiber spacing (10 to 17 nm) in murine adult bones.
      Perlecan/HSPG2, a large linear proteoglycan, was identified to be an essential
      PCM component. The PCM-filled LCS is bone's chromatographic column, where
      fluid/solute transport to and from the osteocytes is regulated. The chemical
      composition, deposition rate, and turnover rate of the osteocyte PCM should be
      further defined to better understand osteocyte physiology and bone metabolism.

PMID- 29349687
TI  - Adjunct and rescue therapies for refractory hypoxemia: prone position, inhaled
      nitric oxide, high frequency oscillation, extra corporeal life support.

PMID- 29349688
TI  - Immunoglobulins and sepsis.

PMID- 29349689
TI  - Suspended in time and space.

PMID- 29349690
TI  - Transthoracic cardiac ultrasound in prone position: a technique variation
      description.

PMID- 29349691
TI  - Subtle trajectories.

PMID- 29349692
TI  - Ascites Due to Constrictive Pericardial Disease Not Appreciated on
      Echocardiogram: A Report of Three Cases.

PMID- 29349693
TI  - Anti-Tumor Necrosis Factor-alpha-Induced Dermatological Complications in a Large
      Cohort of Inflammatory Bowel Disease Patients.
AB  - BACKGROUND/AIMS: The broader use of anti-tumor necrosis factor (TNF) agents in
      inflammatory bowel disease (IBD) has been associated with a high rate of adverse
      reactions. Dermatological complications are among the most common adverse events.
      We assessed the incidence, risk factors, management, and outcome of anti-TNF
      induced dermatological complications in a large cohort of IBD patients. METHODS:
      This was an observational retrospective study at a single tertiary referral
      center. All consecutive adult IBD patients treated with anti-TNF agents between
      2005 and 2015 were identified. Patients who developed at least one dermatological
      complication while on anti-TNF therapy were included. RESULTS: From the 732
      patients treated with anti-TNF agents, 211 (29%) developed at least one
      dermatological complication: 52% women (mean age of 42 +/- 13 years), 85% with
      Crohn's disease, 67% were under infliximab. Median follow-up time under anti-TNF
      therapy was 53 (27-77) months. Dermatological complications recorded were:
      infections (13.5%), psoriasiform lesions (5.3%), injection/infusion reactions
      (3.8%), skin cancer (0.5%), and miscellaneous (5.6%). Overall, female gender (OR
      = 1.658, p = 0.029), smoking (OR = 2.021, p = 0.003), and treatment with an
      infliximab dose of 10 mg/kg (OR = 2.012, p = 0.007) were independent risk factors
      for dermatological complications in multivariable analysis. Female gender (OR =
      3.63, p = 0.017), smoking (OR = 2.846, p = 0.041), and treatment with adalimumab
      (OR = 8.894, p < 0.001) were independently associated with development of
      psoriasiform lesions. Three (3%) patients with infectious complications and 12
      (31%) patients with psoriasiform lesions discontinued anti-TNF therapy
      definitively. CONCLUSIONS: Dermatological manifestations occurred in almost one
      third of our population. Infections were the most common complication, but anti
      TNF-induced psoriasiform lesions were the most common cause for anti-TNF therapy
      definitive discontinuation.

PMID- 29349694
TI  - Endoscopic Ultrasound-Guided Rendezvous Technique for Failed Biliary Cannulation
      in Benign and Resectable Malignant Biliary Disorders.
AB  - BACKGROUND: Endoscopic ultrasound-guided rendezvous technique (EUS-RV) has
      emerged as an effective salvage method for unsuccessful biliary cannulation.
      However, its application for benign and resectable malignant biliary disorders
      has not been fully evaluated. AIMS: To assess the efficacy and safety of EUS-RV
      for benign and resectable malignant biliary disorders. METHODS: This was a
      multicenter prospective study from 12 Japanese referral centers. Patients who
      underwent EUS-RV after failed biliary cannulation for biliary disorder were
      candidates for this study. Inclusion criteria were unsuccessful biliary
      cannulation for therapeutic endoscopic retrograde cholangiopancreatography with
      benign and potentially resectable malignant biliary obstruction. Exclusion
      criteria included unresectable malignant biliary obstruction, inaccessible
      papillae due to surgically altered upper gastrointestinal anatomy or duodenal
      stricture, and previous sphincterotomy and/or biliary stent placement. The
      primary outcome was the technical success rate of biliary cannulation; procedure
      time, adverse events, and clinical outcomes were secondary outcomes. RESULTS:
      Twenty patients were prospectively enrolled. The overall technical success rate
      and median procedure time were 85% and 33 min, respectively. Guidewire
      manipulation using a 4-Fr tapered tip catheter contributed to the success in
      advancing the guidewire into the duodenum. Adverse events were identified in 15%
      patients, including 2 with biliary peritonitis and 1 mild pancreatitis. EUS-RV
      did not affect surgical maneuvers or complications associated with surgery, or
      postoperative course. CONCLUSIONS: EUS-RV may be a safe and feasible salvage
      method for unsuccessful biliary cannulation for benign or resectable malignant
      biliary disorders. Use of a 4-Fr tapered tip catheter may improve the overall EUS
      RV success rate.

PMID- 29349695
TI  - Efficacy of Atopy Patch Testing in Directed Dietary Therapy of Eosinophilic
      Esophagitis: A Pilot Study.
AB  - BACKGROUND: Atopy patch testing (APT) has shown potential for predicting dietary
      food triggers in studies of children and adolescents with eosinophilic
      esophagitis (EoE). AIMS: To assess the efficacy of APT in adults with EoE.
      METHODS: We conducted a prospective open-label pilot study of patients >= 18
      years old with diagnosis of EoE at Mayo Clinic in Rochester, Minnesota, from
      November 2014 to January 2016. All patients underwent patch testing using intact
      food products, followed by a six food elimination diet and stepwise food
      reintroduction. Response to elimination diet was assessed with serial endoscopy
      with biopsies as well as clinical symptoms. APT results were directly compared to
      elimination diet results for assessment of efficacy. Correlation between clinical
      symptoms, endoscopic score, and histology was also qualitatively evaluated.
      RESULTS: Fifty percent of the patients had a positive APT, while only 16% had an
      APT result confirmed histologically during food reintroduction. Sensitivity of
      APT was calculated to be 5.9%, with specificity of 92.0%. Furthermore, we found
      significant qualitative inter-patient heterogeneity in the correlation between
      clinical symptoms, EREFS score, and histology. CONCLUSIONS: APT does not reliably
      predict food triggers identified by food elimination diet in adult patients with
      EoE. As a result, APT does not have a clear role in the evaluation of patients
      with EoE.

PMID- 29349696
TI  - Assessing priming for prosodic representations: Speaking rate, intonational
      phrase boundaries, and pitch accenting.
AB  - Recent work in the literature on prosody presents a puzzle: Some aspects of
      prosody can be primed in production (e.g., speech rate), but others cannot (e.g.,
      intonational phrase boundaries, or IPBs). In three experiments we aimed to
      replicate these effects and identify the source of this dissociation. In
      Experiment 1 we investigated how speaking rate and the presence of an
      intonational boundary in a prime sentence presented auditorily affect the
      production of these aspects of prosody in a target sentence presented visually.
      Analyses of the targets revealed that participants' speaking rates, but not their
      production of boundaries, were affected by the priming manipulation. Experiment 2
      verified whether speakers are more sensitive to IPBs when the boundaries provide
      disambiguating information, and in this different context replicated Experiment 1
      in showing no IPB priming. Experiment 3 tested whether speakers are sensitive to
      another aspect of prosody-pitch accenting-in a similar paradigm. Again, we found
      no evidence that this manipulation affected pitch accenting in target sentences.
      These findings are consistent with earlier research and suggest that aspects of
      prosody that are paralinguistic (like speaking rate) may be more amenable to
      priming than are linguistic aspects of prosody (such as phrase boundaries and
      pitch accenting).

PMID- 29349697
TI  - To share or not to share? Expected pros and cons of data sharing in radiological
      research.
AB  - : The aims of this paper are to illustrate the trend towards data sharing, i.e.
      the regulated availability of the original patient-level data obtained during a
      study, and to discuss the expected advantages (pros) and disadvantages (cons) of
      data sharing in radiological research. Expected pros include the potential for
      verification of original results with alternative or supplementary analyses
      (including estimation of reproducibility), advancement of knowledge by providing
      new results by testing new hypotheses (not explored by the original authors) on
      pre-existing databases, larger scale analyses based on individual-patient data,
      enhanced multidisciplinary cooperation, reduced publication of false studies,
      improved clinical practice, and reduced cost and time for clinical research.
      Expected cons are outlined as the risk that the original authors could not
      exploit the entire potential of the data they obtained, possible failures in
      patients' privacy protection, technical barriers such as the lack of standard
      formats, and possible data misinterpretation. Finally, open issues regarding data
      ownership, the role of individual patients, advocacy groups and funding
      institutions in decision making about sharing of data and images are discussed.
      KEY POINTS: * Regulated availability of patient-level data of published clinical
      studies (data-sharing) is expected. * Expected benefits include
      verification/advancement of knowledge, reduced cost/time of research, clinical
      improvement. * Potential drawbacks include faults in patients' identity
      protection and data misinterpretation.

PMID- 29349698
TI  - Third generation dual-source CT enables accurate diagnosis of coronary restenosis
      in all size stents with low radiation dose and preserved image quality.
AB  - OBJECTIVES: To investigate the diagnostic performance of low dose stent imaging
      in patients with large (>= 3 mm) and small (< 3 mm) calibre stents by third
      generation dual-source CT. METHODS: Symptomatic patients suspected of having in
      stent restenosis (ISR) were prospectively enrolled. Coronary computed tomography
      angiography (CCTA) and invasive coronary angiography (ICA) were performed within
      1 month for correlation. Binary ISR was defined as an in-stent neointimal
      proliferation with diameter stenosis >= 50%. The radiation dose and image quality
      of CCTA were also assessed. RESULTS: Sixty-nine patients with 140 stents were
      ultimately included for analysis. The mean total radiation dose of CCTA was 1.3
      +/- 0.72 mSv in all patients and 0.95 +/- 0.17 mSv in patients with high pitch
      acquisition. The overall diagnostic accuracy of CCTA stent imaging of patient
      based, lesion-based and stent-based analysis was 95.7%, 94.1% and 94.3%,
      respectively. Further, the diagnostic accuracy of CCTA in the small calibre stent
      group (diameter < 3 mm) was slightly lower than that of the large calibre stent
      group (diameter >= 3 mm) (88.5% versus 98.7%, p = 0.01). CONCLUSIONS: Third
      generation dual-source CT enables accurate diagnosis of coronary ISR of both
      large and small calibre stents. Low radiation dose could be achieved with
      preserved image quality. KEY POINTS: * Third-generation DSCT enables accurate
      diagnosis of coronary ISR of all size stents. * Low radiation dose could be
      achieved with preserved image quality. * The diagnostic accuracy of CCTA of small
      calibre stents was 88.5%.

PMID- 29349699
TI  - To evaluate the feasibility of magnetic resonance imaging in predicting unusual
      site ectopic pregnancy: a retrospective cohort study.
AB  - OBJECTIVE: To evaluate the accuracy of pelvic MRI in the diagnosis of unusual
      ectopic pregnancy (EP), when ultrasound (US) examination is inconclusive.
      METHODS: We retrospectively reviewed the medical records of 150 patients with
      suspected EP. Clinical, US and MRI features of 15 unusual EPs were analysed. Two
      radiologists independently reviewed each case resolving by consensus any
      diagnostic discrepancy. Interobserver agreement was assessed using the Cohen
      kappa test. RESULTS: MRI displayed a gestational sac-like structure surrounded by
      a thick wall in all cases. The thick wall displayed hyperintensity in 41 %,
      isointensity in 35 % and hypointensity in 24 % of cases on T1-weighted images.
      Diffusion- and fat saturation T1-weighted images were the most accurate
      sequences, as they enabled identification of 15/15 and 14/15 patients,
      respectively. Although US was false negative in detecting cervical and uterine
      infiltration underlying the caesarean scar, MRI was able to identify the
      invasion. Interobserver agreement was very good for all sequences (kappa=0.892
      1.0). CONCLUSIONS: MRI plays an important role in the early diagnosis of unusual
      EP. It should be considered after negative US findings, providing accurate
      evaluation of the site and the possible infiltration of these lesions, which help
      in the management of these patients. KEY POINTS: * MRI is being increasingly used
      as a problem-solving modality in ectopic pregnancy. * MRI plays an important role
      in early diagnosis of unusual ectopic pregnancy. * Knowledge of MRI features in
      EP is essential to determinate appropriate management.

PMID- 29349700
TI  - Adrenergic and metabolic effects of electrical weapons: review and meta-analysis
      of human data.
AB  - INTRODUCTION: Electronic control with the CEW (conducted electrical weapon) has
      gained widespread acceptance as the preferred force option due to its significant
      injury reduction. However, a CEW application does stress the human body. In the
      case of the CEW, the human body response is similar to the challenge of physical
      exercise combined with emotional stress over a very short time interval. There
      has been concern whether the tension of the skeletal-muscle system together with
      the emotional stress of being exposed to the effects of a CEW, can lead to severe
      metabolic dysfunction. METHODS: A systematic and careful search of the MedLine
      database was performed to find publications describing pathophysiological effects
      of CEWs. Additional publications were collected through a manual search of
      reference lists in retrieved articles. After preliminary exclusions, we carefully
      reviewed the remaining publications and found 24 papers reporting prospective
      human clinical research data on adrenergic, ventilation, or metabolic effects.
      Where there were multiple studies on the same endpoints, we performed meta
      analyses. RESULTS: A CEW exposure provides a clinically insignificant increase in
      heart rate (7.5 BPM) and a drop in both systolic and diastolic blood pressure.
      Alpha-amylase goes down but cortisol levels increase-both epinephrine and
      norepinephrine levels are increased by levels similar to mild exercise. A CEW
      exposure increases ventilation but does not appear to interfere with gas
      exchange. Lactate is increased slightly while the pH is decreased slightly with
      changes equivalent to mild exercise. The lactate and pH changes appear quickly
      and do not appear to be affected by increasing the exposure duration from 5 to 30
      s. CONCLUSIONS: Thorough review and meta-analyses show that electrical weapon
      exposures have mixed and mild adrenergic effects. Ventilation is increased and
      there are metabolic changes similar to mild exercise.

PMID- 29349701
TI  - Chicken Egg Yolk Antibodies Specific for the gamma Chain of Human Hemoglobin for
      Diagnosis of Thalassemia.
AB  - Immunoglobulin Y (IgY) technology was used to generate anti-hemoglobin Bart's (Hb
      Bart's) IgY antibodies (Abs) for development into an enzyme-linked immunosorbent
      assay (ELISA) test for thalassemia diagnosis. Hb Bart's purified from the
      hemolysate of a patient with Hb Bart's hydrops fetalis (homozygous alpha
      thalassemia) was used to immunize a chicken via the pectoralis muscle. After
      water dilution and sodium sulfate precipitation, 40 to 70 mg of IgY could be
      extracted from an egg. IgY, first detected in sera 2 weeks after immunization,
      reached the highest titer at week 4, and the titer remained stable for at least 2
      weeks before declining. The pattern of Ab response in the yolk was the same as in
      the serum but was somewhat delayed. The IgY Abs produced reacted with gamma
      globin, Hb Bart's, Hb F, normal cord hemolysate (Hbs F plus A), and Hb Bart's
      hydrops fetalis (Hbs Bart's plus Portland) and to a lesser degree with beta
      globin, Hb A, Hb A2, and adult hemolysate (Hbs A plus A2), but the Abs did not
      react with alpha globin. Immunoaffinity purification with Hb A coupled to
      Sepharose was used to isolate an unbound IgY that reacted with Hb F, Hb Bart's,
      and gamma globin, and this IgY was used to develop an ELISA test for thalassemia
      diagnosis. The results of direct ELISA analyses of 336 hemolysate samples from
      individuals with various known thalassemia genotypes and phenotypes and from
      healthy individuals confirmed the specificity of the polyclonal Abs for Hbs
      containing Hb F and Hb Bart's. This specificity, which was due to the Abs' strong
      reactivity in cases of pathologic thalassemic diseases and weak reactivity in
      cases of nonpathologic thalassemic diseases, depended on the levels of Hb Bart's
      and Hb F.

PMID- 29349702
TI  - Transcription Factors: Normal and Malignant Development of Blood Cells.

PMID- 29349704
TI  - Peroxisome Proliferator-Activated Receptor gamma and Retinoic Acid Receptor
      Synergistically Up-Regulate the Tumor Suppressor PTEN in Human Promyeloid
      Leukemia Cells.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) and retinoic acid
      receptors (RARs) have been a focus in chemotherapy for human cancers. The tumor
      suppressor PTEN plays a pivotal role in the growth of human cancer cells. We
      investigated whether costimulation of PPARgamma and RAR could synergistically up
      regulate PTEN in human leukemia cells and consequently potentiate the inhibition
      of growth and cell cycle progression of these cells. We found that overexpression
      of PTEN with the adenoviral vector Ad/PTEN caused growth arrest at the G1 phase
      of the cell cycle of HL-60 cells. HL-60 cells treated with either a PPARgamma
      ligand (ciglitazone) or a RAR ligand(all-trans retinoic acid [ATRA]) up-regulated
      PTEN in HL-60 cells. The 2 compounds in combination showed synergistic effects on
      PTEN expression at the protein and messenger RNA levels. Moreover, the
      combination of ciglitazone and ATRA synergistically reduced cell growth rates and
      cell cycle arrest at the G1 phase. Our results suggest that, PPARgamma and RAR
      play an important role in controlling the growth of leukemia cells via the up
      regulation of PTEN.

PMID- 29349703
TI  - Matrix Stiffness: the Conductor of Organ Fibrosis.
AB  - PURPOSE OF REVIEW: Organ fibrosis is a lethal component of scleroderma. The
      hallmark of scleroderma fibrosis is extensive extracellular matrix (ECM)
      deposition by activated myofibroblasts, specialized hyper-contractile cells that
      promote ECM remodeling and matrix stiffening. The purpose of this review is to
      discuss novel mechanistic insight into myofibroblast activation in scleroderma.
      RECENT FINDINGS: Matrix stiffness, traditionally viewed as an end point of organ
      fibrosis, is now recognized as a critical regulator of tissue fibrogenesis that
      hijacks the normal physiologic wound-healing program to promote organ fibrosis.
      Here, we discuss how matrix stiffness orchestrates fibrosis by controlling three
      fundamental pro-fibrotic mechanisms: (a) mechanoactivation of myofibroblasts, (b)
      integrin-mediated latent transforming growth factor beta 1 (TGF-beta1)
      activation, and (c) activation of non-canonical TGF-beta1 signaling pathways. We
      also summarize novel therapeutic targets for anti-fibrotic therapy based on the
      mechanobiology of scleroderma. Future research on mechanobiology of scleroderma
      may lead to important clinical applications such as improved diagnosis and
      treatment of patients with scleroderma and other fibrotic-related diseases.

PMID- 29349705
TI  - Stool cultures at the ICU: get rid of it!
AB  - BACKGROUND: Stool cultures for Campylobacter, Salmonella and Shigella and/or
      Yersinia spp. are frequently ordered in critically ill patients with diarrhea.
      The aim of this study is to analyze the diagnostic yield in a large cohort of
      critically ill patients. Therefore, we performed a cohort study at the Department
      of Intensive Care Medicine of a University Hospital (11 ICUs). RESULTS: From all
      patients who were admitted to the ICU between 2010 and 2015, stool cultures were
      taken from 2.189/36.477 (6%) patients due to diarrhea. Results of all stool
      cultures tested for Campylobacter, Salmonella and Shigella and/or Yersinia spp.
      were analyzed. Overall, 5.747 tests were performed; only six were positive
      (0.1%). In four of these, Campylobacter spp. were detected; diarrhea started
      within 48 h after ICU admission. Two patients with Salmonella spp. detection were
      chronic shedders. On the contrary, testing for Clostridium difficile via GDH- and
      toxin A/B-EIA yielded positive results in 179/2209 (8.1%) tests and revealed
      144/2.189 (6.6%) patients with clinically relevant C. difficile infection.
      CONCLUSIONS: Stool testing for enteric pathogens other than C. difficile should
      be avoided in ICU patients and is only reasonable when diarrhea commenced less
      than 48 h after hospital admission.

PMID- 29349707
TI  - Piperazine clubbed with 2-azetidinone derivatives suppresses proliferation,
      migration and induces apoptosis in human cervical cancer HeLa cells through
      oxidative stress mediated intrinsic mitochondrial pathway.
AB  - Piperazine scaffolds or 2-azetidinone pharmacophores have been reported to show
      anti-cancer activities and apoptosis induction in different types of cancer
      cells. However, the mechanistic studies involve in induction of apoptosis
      addressing these two moieties for human cervical cancer cells remain uncertain.
      The present study emphasizes on the anti-proliferating properties and mechanism
      involved in induction of apoptosis for these structurally related azoles
      derivatives in HeLa cancer cells. 1-Phenylpiperazine clubbed with 2-azetidione
      derivatives (5a-5h) were synthesized, characterized using various spectroscopic
      techniques and evaluated for their in-vitro anti-proliferative activities and
      induction of apoptosis. Further, we also evaluated oxidative stress generated by
      these synthetic derivatives (5a-5h). Cell viability studies revealed that among
      all, the compound N-(3-chloro-2-(3-nitrophenyl)-4-oxoazetidin-1-yl)-2-(4
      phenylpiperazin-1-yl) acetamide 5e remarkably inhibited the growth of HeLa cells
      in a concentration dependent manner having IC50 value of 29.44 +/- 1.46 ug/ml.
      Morphological changes, colonies suppression and inhibition of migration clearly
      showed the antineoplasicity in HeLa cells treated with 5e. Simultaneously,
      phosphatidylserine externalization, DNA fragmentation and cell-cycle arrest
      showed ongoing apoptosis in the HeLa cancer cells induced by compound 5e in
      concentration dependent manner. Additionally, generation of intracellular ROS
      along with the decrease in mitochondrial membrane potential supported that
      compound 5e caused oxidative stress resulting in apoptosis through mitochondria
      mediated pathway. Elevation in the level of cytochrome c and upregulation in
      expression of caspase-3 clearly indicated the involvement of the intrinsic
      pathway of programmed cell death. In brief; compound 5e could serve as a
      promising lead for the development of an effective antitumor agent.

PMID- 29349706
TI  - Effect of the combination of mephedrone plus ethanol on serotonin and dopamine
      release in the nucleus accumbens and medial prefrontal cortex of awake rats.
AB  - Cathinones, such as mephedrone (Meph), are often co-abused with alcoholic drinks.
      In the present study, we investigated the combined effects of Meph plus ethanol
      (EtOH) on neurotransmitter release in the nucleus accumbens (NAc) and the medial
      prefrontal cortex (mPFC). A guide canula was stereotaxically implanted into
      either the NAc or the mPFC of male Sprague-Dawley rats. Seven days after surgery,
      a microdialysis probe was inserted and rats were administered saline, EtOH (1
      g/kg, i.p.), Meph (25 mg/kg, s.c.), or their combination, and dialysates were
      collected. Serotonin (5-HT), dopamine (DA), and their metabolites (5-HIAA, DOPAC
      and HVA) were determined through high-pressure liquid chromatography coupled to
      mass spectrometry. 5-HT and DA peaked 40 min after Meph administration (with or
      without EtOH co-treatment) in both areas. EtOH combined with Meph increased the 5
      HT release compared with the rats receiving Meph alone (85% in NAc, 65% in mPFC),
      although the overall change in the area under the curve only reached statistical
      significance in the NAc. In mPFC, the increased release of 5-HT lasted longer in
      the combination than that in the Meph group. Moreover, EtOH potentiated the
      psychostimulant effect of Meph measured as a locomotor activity. Given that both
      5-HT and DA are also related with reward and impulsivity, the observed effects
      point to an increased risk of abuse liability when combining Meph with EtOH
      compared with consuming these drugs alone.

PMID- 29349708
TI  - Cost-Effectiveness of Empagliflozin for the Treatment of Patients with Type 2
      Diabetes Mellitus at Increased Cardiovascular Risk in Greece.
AB  - BACKGROUND AND OBJECTIVE: Type 2 diabetes mellitus (T2DM) is frequently
      associated with co-morbidities that exacerbate cardiovascular (CV) risk. CV
      disease is the leading cause of death in people with diabetes across the world
      and accounts for approximately half the deaths in the T2DM population. Hence, the
      objective of present study was to evaluate the cost-effectiveness of
      empagliflozin, in addition to standard of care (SoC), for the treatment of adult
      patients with T2DM and high CV risk in Greece. METHODS: A health economic model
      was used to project clinical and economic outcomes of patients receiving
      empagliflozin plus SoC compared with those receiving SoC alone over a lifetime
      horizon. CV and renal event rates were derived from patient level data from the
      EMPA-REG-OUTCOME(r) trial by fitting time-dependent parametric survival
      functions. 5000 individual patient profiles randomly sampled from the trial were
      simulated using a time-to-event approach. Model extrapolated outcomes included
      life years (LYs), quality-adjusted life years (QALYs), costs, and incremental
      cost-effectiveness ratio (ICER). Following a Greek third-party payer perspective,
      only direct medical costs related to drug acquisition as well as fatal and non
      fatal diabetes-related complications were considered (?2016). Cost units and
      utility data were extracted from the literature and publicly available official
      sources. Sensitivity analyses explored the impact of changes in input data.
      RESULTS: Over a patient's lifetime, empagliflozin was predicted to result in
      longer mean survival (14.01 LY vs. 11.87 LY with SoC) and reduced rate of
      clinical events accumulating 7.75 QALYs versus 6.83 QALYs on SoC alone at
      additional costs of ?4235. The generated ICER of empagliflozin was ?4633 per QALY
      gained. One-way sensitivity analysis confirmed empagliflozin's cost-effective
      profile. At the defined willingness-to-pay threshold of ?34,000 per QALY gained,
      probabilistic sensitivity analysis showed that empagliflozin was estimated to
      have a 100% probability of being cost-effective relative to SoC. CONCLUSIONS:
      Empagliflozin added to SoC was estimated to be a highly cost-effective treatment
      option for the treatment of T2DM in adults with increased CV disease risk in
      Greece.

PMID- 29349709
TI  - The host response in critically ill sepsis patients on statin therapy: a
      prospective observational study.
AB  - BACKGROUND: Statins can exert pleiotropic anti-inflammatory, vascular protective
      and anticoagulant effects, which in theory could improve the dysregulated host
      response during sepsis. We aimed to determine the association between prior
      statin use and host response characteristics in critically ill patients with
      sepsis. METHODS: We performed a prospective observational study in 1060 patients
      admitted with sepsis to the mixed intensive care units (ICUs) of two hospitals in
      the Netherlands between January 2011 and July 2013. Of these, 351 patients (33%)
      were on statin therapy before admission. The host response was evaluated by
      measuring 23 biomarkers providing insight into key pathways implicated in sepsis
      pathogenesis and by analyzing whole-blood leukocyte transcriptomes in samples
      obtained within 24 h after ICU admission. To account for indication bias, a
      propensity score-matched cohort was created (N = 194 in both groups for protein
      biomarkers and N = 95 in both groups for gene expression analysis). RESULTS:
      Prior statin use was not associated with an altered mortality up to 90 days after
      admission (38.0 vs. 39.7% in the non-statin users in the propensity-matched
      analysis). Statin use did not modify systemic inflammatory responses, activation
      of the vascular endothelium or the coagulation system. The blood leukocyte
      genomic response, characterized by over-expression of genes involved in
      inflammatory and innate immune signaling pathways as well as under-expression of
      genes associated to T cell function, was not different between patients with and
      without prior statin use. CONCLUSIONS: Statin therapy is not associated with a
      modified host response in sepsis patients on admission to the ICU.

PMID- 29349710
TI  - Digital image analysis of Ki67 proliferation index in breast cancer using virtual
      dual staining on whole tissue sections: clinical validation and inter-platform
      agreement.
AB  - PURPOSE: The Ki67 proliferation index is a prognostic and predictive marker in
      breast cancer. Manual scoring is prone to inter- and intra-observer variability.
      The aims of this study were to clinically validate digital image analysis (DIA)
      of Ki67 using virtual dual staining (VDS) on whole tissue sections and to assess
      inter-platform agreement between two independent DIA platforms. METHODS: Serial
      whole tissue sections of 154 consecutive invasive breast carcinomas were stained
      for Ki67 and cytokeratin 8/18 with immunohistochemistry in a clinical setting.
      Ki67 proliferation index was determined using two independent DIA platforms,
      implementing VDS to identify tumor tissue. Manual Ki67 score was determined using
      a standardized manual counting protocol. Inter-observer agreement between manual
      and DIA scores and inter-platform agreement between both DIA platforms were
      determined and calculated using Spearman's correlation coefficients. Correlations
      and agreement were assessed with scatterplots and Bland-Altman plots. RESULTS:
      Spearman's correlation coefficients were 0.94 (p < 0.001) for inter-observer
      agreement between manual counting and platform A, 0.93 (p < 0.001) between manual
      counting and platform B, and 0.96 (p < 0.001) for inter-platform agreement.
      Scatterplots and Bland-Altman plots revealed no skewness within specific data
      ranges. In the few cases with >= 10% difference between manual counting and DIA,
      results by both platforms were similar. CONCLUSIONS: DIA using VDS is an accurate
      method to determine the Ki67 proliferation index in breast cancer, as an
      alternative to manual scoring of whole sections in clinical practice. Inter
      platform agreement between two different DIA platforms was excellent, suggesting
      vendor-independent clinical implementability.

PMID- 29349711
TI  - Impact of an embedded genetic counselor on breast cancer treatment.
AB  - BACKGROUND: We predicted that embedding a genetic counselor within our breast
      practice would improve identification of high-risk individuals, timeliness of
      care, and appropriateness of surgical decision making. The aim of this study is
      to compare cancer care between 2012 and 2014, prior to embedding a genetic
      counselor in the breast center and following the intervention, respectively.
      METHODS: A retrospective review of patients diagnosed with breast cancer in 2012
      (n = 471) and 2014 (n = 440) was performed to assess patterns of medical genetics
      referral, compliance with referral, genetic testing findings, and impact on
      treatment. RESULTS: Between 2012 and 2014, patients were 49% more likely to be
      referred to genetics, 66% more likely to follow through with their genetic
      counseling appointment, experienced a 73% reduction in wait times to genetic
      counseling visits and 69% more likely to have genetic testing results prior to
      surgery. Notably, while the number of genetic mutations identified was in the
      expected range over both time periods (9% of those tested in 2012 vs. 6.6% of
      those tested in 2014), there was a 31% reduction in time to treatment in 2014 vs.
      2012. CONCLUSION: Awareness of germline genetic mutations is critical in surgical
      decision making for newly diagnosed breast cancer patients. Having an experienced
      genetics specialist on site in a busy surgical breast clinic allows for timely
      access to genetic counseling and testing, and may have influenced time to
      treatment in our institution.

PMID- 29349712
TI  - Highly favorable physiological responses to concurrent resistance and high
      intensity interval training during chemotherapy: the OptiTrain breast cancer
      trial.
AB  - BACKGROUND: Advanced therapeutic strategies are often accompanied by significant
      adverse effects, which warrant equally progressive countermeasures. Physical
      exercise has proven an effective intervention to improve physical function and
      reduce fatigue in patients undergoing chemotherapy. Effects of high-intensity
      interval training (HIIT) in this population are not well established although
      HIIT has proven effective in other clinical populations. The aim of the OptiTrain
      trial was to examine the effects of concurrent resistance and high-intensity
      interval training (RT-HIIT) or concurrent moderate-intensity aerobic and high
      intensity interval training (AT-HIIT), to usual care (UC) on pain sensitivity and
      physiological outcomes in patients with breast cancer during chemotherapy.
      METHODS: Two hundred and forty women were randomized to 16 weeks of RT-HIIT, AT
      HIIT, or UC. OUTCOMES: cardiorespiratory fitness, muscle strength, body mass,
      hemoglobin levels, and pressure-pain threshold. RESULTS: Pre- to post
      intervention, RT-HIIT (ES = 0.41) and AT-HIIT (ES = 0.42) prevented the reduced
      cardiorespiratory fitness found with UC. Handgrip strength (surgery side: RT-HIIT
      vs. UC: ES = 0.41, RT-HIIT vs. AT-HIIT: ES = 0.28; non-surgery side: RT-HIIT vs.
      UC: ES = 0.35, RT-HIIT vs. AT-HIIT: ES = 0.22) and lower-limb muscle strength (RT
      HIIT vs. UC: ES = 0.66, RT-HIIT vs. AT-HIIT: ES = 0.23) were significantly
      improved in the RT-HIIT. Increases in body mass were smaller in RT-HIIT (ES = -
      0.16) and AT-HIIT (ES = - 0.16) versus UC. RT-HIIT reported higher pressure-pain
      thresholds than UC (trapezius: ES = 0.46, gluteus: ES = 0.53) and AT-HIIT
      (trapezius: ES = 0.30). CONCLUSION: Sixteen weeks of RT-HIIT significantly
      improved muscle strength and reduced pain sensitivity. Both exercise programs
      were well tolerated and were equally efficient in preventing increases in body
      mass and in preventing declines in cardiorespiratory fitness. These results
      highlight the importance of implementing a combination of resistance and high
      intensity interval training during chemotherapy for women with breast cancer.

PMID- 29349713
TI  - Patient-reported outcomes of catheter-based accelerated partial breast
      brachytherapy and whole breast irradiation, a single institution experience.
AB  - PURPOSE: Accelerated partial breast irradiation (APBI) and whole breast
      irradiation (WBI) are treatment options for early-stage breast cancer. The
      purpose of this study was to compare patient-reported-outcomes (PRO) between
      patients receiving multi-channel intra-cavitary brachytherapy APBI or WBI.
      METHODS: Between 2012 and 2015, 131 patients with ductal carcinoma in situ (DCIS)
      or early stage invasive breast cancer were treated with adjuvant APBI (64) or WBI
      (67) and participated in a PRO questionnaire. The linear analog scale assessment
      (LASA), harvard breast cosmesis scale (HBCS), PRO-common terminology criteria for
      adverse events- PRO (PRO-CTCAE), and breast cancer treatment outcome scale
      (BCTOS) were used to assess quality of life (QoL), pain, fatigue, aesthetic and
      functional status, and breast cosmesis. Comparisons of PROs were performed using
      t-tests, Wilcoxon rank-sum, Chi square, Fisher exact test, and regression
      methods. RESULTS: Median follow-up from completion of radiotherapy and
      questionnaire completion was 13.3 months. There was no significant difference in
      QoL, pain, or fatigue severity, as assessed by the LASA, between treatment groups
      (p > 0.05). No factors were found to be predictive of overall QoL on regression
      analysis. BCTOS health-related QoL scores were similar between treatment groups
      (p = 0.52).The majority of APBI and WBI patients reported excellent/good breast
      cosmesis, 88.5% versus 93.7% (p = 0.37). Skin color change (p = 0.011) and breast
      elevation (p = 0.01) relative to baseline were more common in the group receiving
      WBI. CONCLUSIONS: APBI and WBI were both associated with favorable patient
      reported outcomes in early follow-up. APBI resulted in a lesser degree of patient
      reported skin color change and breast elevation relative to baseline.

PMID- 29349714
TI  - DBDA as a Novel Matrix for the Analyses of Small Molecules and Quantification of
      Fatty Acids by Negative Ion MALDI-TOF MS.
AB  - Matrix interference ions in low mass range has always been a concern when using
      matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      (MALDI-TOF MS) to analyze small molecules (<500 Da). In this work, a novel
      matrix, N1,N4-dibenzylidenebenzene-1,4-diamine (DBDA) was synthesized for the
      analyses of small molecules by negative ion MALDI-TOF MS. Notably, only neat ions
      ([M-H]-) of fatty acids without matrix interference appeared in the mass spectra
      and the limit of detection (LOD) reached 0.3 fmol. DBDA also has great
      performance towards other small molecules such as amino acids, peptides, and
      nucleotide. Furthermore, with this novel matrix, the free fatty acids in serum
      were quantitatively analyzed based on the correlation curves with correlation
      coefficient of 0.99. In addition, UV-Vis experiments and molecular orbital
      calculations were performed to explore mechanism about DBDA used as matrix in the
      negative ion mode. The present work shows that the DBDA matrix is a highly
      sensitive matrix with few interference ions for analysis of small molecules.
      Meanwhile, DBDA is able to precisely quantify the fatty acids in real biological
      samples. Graphical Abstract ?.

PMID- 29349715
TI  - "Sex Is a sin": Afro-Caribbean Parent and Teen Perspectives on Sex Conversations.
AB  - This study characterized (a) mothers' childhood and teenage experiences with sex
      conversations and (b) families' perceptions of current parent-child sex
      conversations within two underserved Afro-Caribbean communities in the U.S.
      Fourteen dyads comprised of Haitian and Jamaican mothers and teens (aged 14-18)
      living in Miami, Florida, completed semi-structured interviews sharing their
      experiences with sex conversations. Researchers analyzed data using thematic
      content analysis. Mothers' mean age was 41.85 years, (SD = 5.50) and teens' mean
      age was 16.35 years, (SD = 1.31). Most mothers reported forbidden or little
      childhood experiences with parent-child sex conversations. They affected their
      sexual attitudes, behaviors, and ability to discuss sex with their children.
      Although some mothers benefited from educational and skill development others
      shared fear-based messages with their children that some teens believed adversely
      affected the mother-child relationship quality. Culturally appropriate, skill
      based approaches are necessary to improve families' communication self-efficacy
      for healthy sex conversations to occur in Afro-Caribbean families.

PMID- 29349716
TI  - Detection of bovine carriers of Leptospira by serological, bacteriological, and
      molecular tools.
AB  - Bovine leptospirosis is an important infectious disease that causes reproductive
      problems and economic risks, particularly in the tropics. The present study aimed
      to determine the extent of Leptospira infection among bovines on a slaughterhouse
      from Rio de Janeiro, Brazil via serological, bacteriological, and molecular
      tests. Two hundred eight bovines were examined in total, and we obtained 208
      blood samples for serology, 198 urine samples collected via direct bladder
      puncture for polymerase chain reaction (PCR) and culture, 208 kidney samples (one
      from each animal) for PCR and culture, and 92 vaginal fluid samples from sterile
      swabs for PCR and culture. Serology demonstrated that 77/208 (37%) of the animals
      presented anti-Leptospira antibodies. Serogroup Sejroe was by far the most
      common. One hundrd thirty-three animals (63.9%) were PCR positive in at least one
      of the tested samples and were considered as Leptospira carriers. Furthermore,
      ten isolates were obtained by pure culture, all of them from urine samples.
      Bovine leptospirosis is widely prevalent, and the occurrence of renal carriers
      was unexpectedly much higher than generally reported.

PMID- 29349717
TI  - Analysis of Candidate Genes at the IBGC1 Locus Associated with Idiopathic Basal
      Ganglia Calcification ("Fahr" Disease').
AB  - Basal ganglia calcification (striatopallidodentate calcifications) can be caused
      by several systemic and neurological disorders. Familial Idiopathic Basal Ganglia
      Calcification (IBGC, "Fahr" disease'), is characterized by basal ganglia and
      extrabasal ganglia calcifications, parkinsonism and neuropsychiatric symptoms.
      Because of an increased use of neuroimaging procedures, calcifications of the
      basal ganglia are visualized more often and precociously. In 1999, a major
      American family with IBGC was linked to a locus on chromosome 14q (IBGC1).
      Another small kindred, from Spain, has also been reported as possibly linked to
      this locus. Here we report the main findings of the first 30 candidate genes
      sequenced at the IBGC1 locus during the process of searching for a mutation
      responsible for familial IBGC. During the sequencing process, we identified a
      heterozygous nonsynonymous single nucleotide polymorphism (exon 20 of the MGEA6/c
      TAGE gene) shared by the affected and not present in the controls. This SNP was
      randomly screened in the general population (348 chromosomes) in a minor allele
      frequency to 0.0058 (two heterozygous among 174 subjects). Another variation in
      this gene, in the exon 9, was found in the Spanish family. However, this
      variation was extremely common in the general population. Functional and
      population studies are necessary to fully access the implications of the MGEA6
      gene in familial IBGC, and a complete sequencing of the IBGC1 locus will be
      necessary to define a gene responsible for familial IBGC.

PMID- 29349718
TI  - Erratum to: The Innate Facet of the Brain: Human Neurons Express TLR3 and Sense
      Viral dsRNA.

PMID- 29349719
TI  - Shifts in the importance of the species pool and environmental controls of
      epiphytic bryophyte richness across multiple scales.
AB  - Species richness is influenced by a nested set of environmental factors, but how
      do these factors interact across several scales? Our main aim is to disentangle
      the relative importance of environmental filters and the species pool on the
      richness of epiphytic bryophytes across spatial scales. To do so, we sampled
      epiphytic bryophytes in 43 oak forests across the northwest of the Iberian
      Peninsula. As predictors we used climate, descriptors of forest structure and
      micro-environment. We applied structural equation modeling to relate these
      variables with richness and cover at three scales: locality (forest), stand
      (three stands per forest), and sample (a quadrate in a tree). We assumed top-down
      relationships, so that large-scale variables influenced lower scale variables,
      and in which cover directly influenced richness. Richness at the next larger
      scale (locality to stand and stand to sample) is considered a surrogate of the
      species pool and included as a predictor of richness at the next smaller scale.
      Environmental variables explain locality richness, but as we decrease the spatial
      scale, its importance decreases and the dependence on species pool increases. In
      addition, we found unexpected bottom-up relationships (between micro-scale
      environment to locality richness). Our results point to the scale dependence of
      niche vs. neutral processes: niche processes are important at the locality
      (forest) scale, while neutral processes are significant at the small (sample)
      scale. We propose a modified conceptualization of the factors influencing
      biodiversity at different spatial scales by adding links across different scales
      (between micro-environment and locality-scale richness in our study).

PMID- 29349720
TI  - Differential Effects of Formal and Informal Gambling on Symptoms of Problem
      Gambling During Voluntary Self-Exclusion.
AB  - Voluntary self-exclusion (VSE) programs enable problem gamblers to engage in a
      break from casino-based gambling. The current study analyzed the effects of a VSE
      program in British Columbia, Canada on problem gambling symptoms and the
      comparative reductions in problem gambling symptoms when participants abstained
      from gambling, continued to participate in non-casino based gambling, or
      attempted to violate their exclusion contract. 269 participants completed two
      telephone interviews over a 6-month period. Participants were administered the
      Problem Gambling Severity Index (PGSI). Substantial reductions in PGSI scores
      were observed after 6 months. Program violators had significantly smaller PGSI
      Difference Scores by Time 2 compared to those who continued to gamble outside of
      the casino and those who completely abstained from all gambling. There were no
      significant differences between those who gambled informally and those who
      abstained. A multiple regression identified that while access to counselling and
      length of enrollment also contributed to the reduction in PGSI scores, violation
      attempts were most strongly associated with smaller reductions in symptoms of
      problem gambling. These results imply that some gamblers can successfully engage
      in non-casino based forms of gambling and still experience reductions in symptoms
      of problem gambling. Future analyses will explore characteristics associated with
      group membership that may help to identify which participants can successfully
      engage in non-casino based gambling without re-triggering symptoms of problem
      gambling.

PMID- 29349721
TI  - Effects of load on the acute response of muscles proximal and distal to blood
      flow restriction.
AB  - To determine the effects of load and blood flow restriction (BFR) on muscular
      responses, we asked 12 participants to perform chest presses under four different
      conditions [30/0, 30/40, 50/0, and 50/40, presented as percentage one-repetition
      maximum (1RM)/percentage arterial occlusion pressure (AOP)]. Muscle thickness
      increased pre- to post-exercise [chest: mean 0.29, 95% confidence interval (CI)
      0.21, 0.37 cm; triceps: mean 0.44, 95% CI 0.34, 0.54 cm], remaining elevated for
      15 min post-exercise. Electromyography amplitude was greater with 50% 1RM and
      increased over time for the first three repetitions of each set of chest presses.
      The last three repetitions differed across time only. AOP increased from pre- to
      post-exercise, augmented by BFR [30/0: mean 31, 95% CI 18, 44 mmHg; 30/40: mean
      39, 95% CI 28, 50 mmHg; 50/0: mean 32, 95% CI 23, 41 mmHg; 50/40: mean 46, 95% CI
      32, 59 mmHg). Tranquility decreased and physical exhaustion increased from the
      pre- to post-condition, with both parameters returning to the baseline 15 min
      post-exercise level. In conclusion, load and BFR do not elicit meaningful
      differences in the acute response of chest press exercise taken to failure.

PMID- 29349722
TI  - Bystin (BYSL) as a possible marker of severe hypoxic-ischemic changes in
      neuropathological examination of forensic cases.
AB  - Bystin (BYSL) is a 306-amino acid protein encoded in humans by the BYSL gene
      located on the 6p21.1 chromosome. It is conserved across a wide range of
      eukaryotes. BYSL was reported to be a sensitive marker for the reactive
      astrocytes induced by ischemia/reperfusion and chemical hypoxia in vitro and is
      considered to be one of the common characteristics of astrogliosis. In our study
      we examined whether BYSL could be used as a marker for hypoxic-ischemic changes
      in forensic cases. Groups suspected of acute hypoxic-ischemic changes presented
      strong BYSL expression in the cytoplasm of neocortical neurons especially in
      layers 3-5, that seemed to be short-lasting. In the hypoxic-ischemic-reperfusion
      group we did not find BYSL expression. BYSL expression in the cytoplasm of
      cortical neurons was minimal in the control group (cardiac arrest). BYSL seems to
      be a promising early marker of severe hypoxic-ischemic changes in
      neuropathological examination of forensic cases and certainly requires further
      studies.

PMID- 29349723
TI  - Species diversity and tissue specific dispersal of necrophagous Diptera on human
      bodies.
AB  - In forensic entomology, many studies analyze fly activity and succession on dead
      bodies by using pig cadavers and a variety of small baited traps. Data on real
      human bodies are very rare. To address this shortcoming, we analyzed the fly
      fauna of 51 human bodies in Germany. Sex, age, place of discovery, and presumed
      time of death were noted. Larvae were sampled during autopsy according to body
      region or tissue. For every infested region, the total number of fly larvae were
      estimated and classified into categories of 1-10, 11-50, and 50+. All samples
      were identified to the species level. Besides a descriptive analysis of their
      occurrence patterns, a categorical PCA was performed, and multispecies
      generalized linear models and a latent variable model were run. Our results
      highlight the most forensically important blow flies on human bodies in Central
      Europe (Lucilia sericata, L. ampullacea, Phormia regina, Calliphora vicina);
      prove, for the first time, the general transferability of species lists based on
      succession studies on pig cadavers; recommend a certain set of species, such as
      the so-far neglected L. ampullacea, for future developmental studies; and reveal
      competitive occurrence of up to six species on the same body as a potential
      factor of influence. Assignment to a certain body region was often possible and
      our data clearly indicate certain tissues, e.g. brain, as of high interest for
      future developmental studies. Focusing on real scenario settings helps direct
      research to forensically relevant questions and appraises the plausibility of
      vital laboratory studies.

PMID- 29349724
TI  - Analyzing similarities in genome sequences.
AB  - This article investigates aspects of similarity between complete sequences of
      mitochondrial DNA by determining the distribution of the relative frequencies of
      words with different lengths and the characteristics of their relevance
      throughout the sequences. The degree of similarity is obtained by comparing the
      distances between words contained within these sequences. Our results indicate
      that the best groupings among different species depend on the lengths of words
      and their respective relative frequencies. We also observed that the longer the
      word the more consistent the grouping between the sequences becomes. The
      application of our results, together with the perspective of analyzing DNA
      sequences belonging to a single biological species, may be important for the
      construction of phylogenetic trees, which are appropriate structures for
      understanding the evolutionary history of the species.

PMID- 29349725
TI  - Ki67 Proliferative Index in Carcinoid Tumors Involving Ovary.
AB  - Primary ovarian carcinoid tumors are rare neoplasms that constitute less than
      0.1% of all ovarian carcinomas. However, carcinoid tumors metastatic to ovaries
      are more common. Cell proliferative rate is an important factor in the
      determination of neuroendocrine tumor prognosis. Limited data are available as
      regards Ki67 proliferation index in predicting the physiological features of
      carcinoid tumors involving the ovary. Pathology files of Mayo Clinic Rochester
      (1995-2014) were searched, and clinical information was collected from medical
      records. All cases were stained with an antibody against Ki67, and digital
      analysis was performed with digital imaging analysis. A total of 36 cases (median
      age 64 years, range 33-83 years), including 9 primary (median age 68 years, range
      33-73 years) and 27 metastatic carcinoid cases (median age 64 years, range 36-83
      years), were investigated in the current study. Seven out of nine (77.8%) primary
      ovarian carcinoids are associated with mature teratoma. Twenty two metastatic
      carcinoids (81.5%) were from the GI tract, four (14.8%) from the pancreas, and
      one (3.7%) from the posterior thorax location. There was significant difference
      of Ki67 index between primary (median 2.3%, range, 0.6-8.4%) and metastatic
      carcinoid tumors (median 9.7%, range, 1.3-46.7%) (p = 0.002). The survival time
      is much shorter among patients with metastatic carcinoid tumor (median survival
      5.8 years) comparing to primary ovarian carcinoid tumor (median 14.2 years) (p =
      0.0005). A strong association between Ki67 index and patient survival time was
      identified (Hazard ratio for 1-percentage point increase 1.11, p = 0.001).
      Comparing to primary ovarian carcinoid tumor, metastatic carcinoid usually
      exhibits a higher Ki67 index and a worse outcome.

PMID- 29349726
TI  - Fungal Respiratory Infections in Cystic Fibrosis (CF): Recent Progress and Future
      Research Agenda.

PMID- 29349727
TI  - Lifestyles of Patients with Functional Psychosis Compared to Those of a Sample of
      the Regional General Population: Findings from a Study in a Community Mental
      Health Service of the Veneto Region, Italy.
AB  - Unhealthy lifestyles contribute, with other risk factors, to the high prevalence
      of mortality and physical comorbidity among mental patients compared to the
      general population. We collected data on the lifestyles of 193 subjects with
      psychosis in contact with a Community Mental Health Service in north-eastern
      Italy and compared them with a representative sample (total: 3219 subjects) of
      the general population of the same region. Diet, exercise, smoking and alcohol
      consumption were worse in mental patients. A higher percentage of patients was
      overweight or obese. The associations between socio-demographic and lifestyles
      variables showed that older patients exercise less, female patients tend to smoke
      and use alcohol less, while more educated patients tend to have higher alcohol
      consumption levels. Mental patients have unhealthier lifestyles and they appear
      to be more refractory to recommendations than the general population, indicating
      the necessity of specific health promotion programmes in this population.

PMID- 29349728
TI  - Correction to: Mental Health Needs and Psychoactive Drug Use in a User Population
      of the Family Health Strategy (FHS) in Ribeirao Preto, Sao Paulo, Brazil.
AB  - The original version of this article unfortunately published without
      acknowledgement. The funding information and grant number is given below: Funding
      Research supported by Research in Public for the National Health Care System (PP
      SUS), Grant number 12/51732-9.

PMID- 29349729
TI  - Witnessing the advance of science and technology in life sciences in the new era.

PMID- 29349730
TI  - CCN5 in alveolar epithelial proliferation and differentiation during neonatal
      lung oxygen injury.
AB  - Lung immaturity is the major cause of morbidity and mortality in premature
      infants, especially those born <28 weeks of gestation. These infants are at high
      risk of developing respiratory distress syndrome (RDS), a lung disease caused by
      insufficient surfactant production and immaturity of saccular/alveolar type II
      epithelial cells in the lung. RDS treatment includes oxygen and respiratory
      support that improve survival but also increase the risk for bronchopulmonary
      dysplasia (BPD), a chronic lung disease characterized by arrested
      alveolarization, airway hyperreactivity, and pulmonary hypertension. The
      mechanisms regulating normal alveolar development and how injury disrupts normal
      development to cause BPD are not well understood. We examined the role of the
      matricellular protein CCN5 (Cysteine-rich protein 61/Connective tissue growth
      factor/Nephroblastoma-overexpressed protein) in the development of BPD. Cultured
      non-proliferating alveolar type II cells expressed low levels of CCN5 protein,
      and displayed higher levels during proliferation. siRNA targeting of CCN5 reduced
      alveolar type II cell proliferation and migration in cell culture. In a mouse
      model of hyperoxia-induced BPD, CCN5 protein was increased only in proliferating
      alveolar type I cells. Alveolar epithelial cells co-expressing markers of type II
      cells and type I cells also appeared. The results suggest that hyperoxic injury
      in immature lungs induces proliferation of type I cells and trans-differentiation
      of type II cells into type I cells. We propose that the mechanism of the injury
      response in BPD includes CCN5 expression. Study of CCN5 in neonatal alveolar
      injury will further our understanding of BPD pathophysiology while providing a
      mechanistic foundation for therapeutic approaches.

PMID- 29349731
TI  - Membranous nephropathy associated with pregnancy: an anti-phospholipase A2
      receptor antibody-positive case report.
AB  - Pregnancy and membranous nephropathy (MN) can occur concurrently with nephrotic
      syndrome. However, the pathophysiology of MN associated with pregnancy remains
      unclear, including the involvement of anti-M-type phospholipase A2 receptor
      (PLA2R) antibody, the major antigen of idiopathic MN (iMN). A treatment for the
      condition is also not established. We present the case of a 43-year-old pregnant
      female with incidental proteinuria and hypoalbuminemia. We made a diagnosis of
      nephrotic syndrome at 11 week gestation. Renal biopsy revealed iMN using
      predominant granular staining of IgG4 along the glomerular basement membrane. No
      secondary cause was identified. Oral glucocorticoid therapy was started from 17
      week gestation and induced complete remission at 28 week gestation. A healthy
      infant was born at 38 week gestation. Glucocorticoid therapy was stopped
      postpartum without MN relapse. Anti-PLA2R antibody was later found to be positive
      using serum reserved from before treatment. In conclusion, we presented the case
      of a pregnant woman with iMN and anti-PLA2R antibodies, whose nephrotic syndrome
      was successfully controlled with oral glucocorticoids to reach complete
      remission, even after tapering off the medication. Pregnancy per se might be
      associated with iMN onset.

PMID- 29349732
TI  - Membranous glomerulonephritis with an LMNA mutation.
AB  - We had encountered the case of membranous glomerulonephritis (MGN) with dilated
      cardiomyopathy due to LMNA gene mutation. LMNA mutation was known as a cause of
      'laminopathy' such as dilated cardiomyopathy, muscular dystrophy, neuropathy and
      so on. LMNA gene might be a candidate of genetic basis in cryptogenic MGN.

PMID- 29349733
TI  - Point-of-care ultrasound (POCUS) of the upper airway.
AB  - Airway management is a critical skill in the practice of several medical
      specialities including anesthesia, emergency medicine, and critical care. Over
      the years mounting evidence has showed an increasing role of ultrasound (US) in
      airway management. The objective of this narrative review is to provide an
      overview of the indications for point-of-care ultrasound (POCUS) of the upper
      airway. The use of US to guide and assist clinical airway management has
      potential benefits for both provider and patient. Ultrasound can be utilized to
      determine airway size and predict the appropriate diameter of single-lumen
      endotracheal tubes (ETTs), double-lumen ETTs, and tracheostomy tubes.
      Ultrasonography can differentiate tracheal, esophageal, and endobronchial
      intubation. Ultrasonography of the neck can accurately localize the cricothyroid
      membrane for emergency airway access and similarly identify tracheal rings for US
      guided tracheostomy. In addition, US can identify vocal cord dysfunction and
      pathology before induction of anesthesia. A rapidly growing body of evidence
      showing ultrasonography used in conjunction with hands-on management of the
      airway may benefit patient care. Increasing awareness and use of POCUS for many
      indications have resulted in technologic advancements and increased accessibility
      and portability. Upper airway POCUS has the potential to become the first-line
      non-invasive adjunct assessment tool in airway management.

PMID- 29349734
TI  - Alternative soilless media using olive-mill and paper waste for growing
      ornamental plants.
AB  - Peat-based growing media are not ecologically sustainable and peat extraction
      threatens sensitive peatland ecosystem. In this study, olive-stone waste (OSW)
      and paper waste (PW) were used in different ratios-as growing media-for
      ornamental crop production, as peat (P) substitutes. Marigold (Calendula
      officinalis L.), petunia (Petunia x hybrita L.) and matthiola (Matthiola incana
      L.) plants were grown in (1) P (100%), (2) P:OSW (90%:10%), (3) P:OSW (70%:30%),
      and (4) P:OSW:PW (60%:20%:20%). The physicochemical properties of these
      substrates and the effects on plant growth were determined. The addition of 10
      30% OSW into the substrate increased marigold height compared to plants grown in
      100% peat. No differences in plant size, plant biomass (leaves and flowers), and
      dry matter content were found. Adding PW, in combination with OSW, maintained
      marigold height and total number of flowers produced to similar levels as in
      plants grown in 100% peat. In matthiola, adding 30% OSW into the substrate
      reduced plant size and fresh weight, but not plant height. No differences were
      observed when plants grew in lower OSW (i.e., 10%) content. Petunia's height, its
      total number of flowers and flower earliness (flower opening) were increased in
      the presence of OSW compared to the plants grown in 100% peat. The addition of
      OSW did not affect petunia's size and fresh weight among treatments. The addition
      of PW suppressed several plant growth-related parameters for both matthiola and
      petunia. The insertion of OSW did not change leaf chlorophyll content whereas the
      presence of PW decreased chlorophylls for marigold, petunia, and matthiola. Both
      OSW and PW altered the content of total phenolics and antioxidant capacity of 2,2
      diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6
      sulphonic acid) (ABTS) in leaves and flowers for marigold and petunia. Both 30%
      OSW and PW increased antioxidative enzyme metabolism due to the increased damage
      index and lipid peroxidation observed in plants. Leaf N and P content decreased
      in PW-based media, while matthiola displayed visual phytotoxicity symptoms when
      PW was added into the substrate. The present work indicates that up to 30% of OSW
      can replace peat for marigold and petunia growing and only up to 10% of OSW for
      matthiola, while the addition of PW on top of OSW is not recommended, so further
      research is needed.

PMID- 29349735
TI  - ICT, openness and CO2 emissions in Africa.
AB  - This study investigates how information and communication technology (ICT)
      complements globalisation in order to influence CO2 emissions in 44 Sub-Saharan
      African countries over the period 2000-2012. ICT is measured with internet
      penetration and mobile phone penetration whereas globalisation is designated in
      terms of trade and financial openness. The empirical evidence is based on the
      generalised method of moments. The findings broadly show that ICT can be employed
      to dampen the potentially negative effect of globalisation on environmental
      degradation like CO2 emissions. Practical, policy and theoretical implications
      are discussed.

PMID- 29349736
TI  - Application of experimental design for the optimization of artificial neural
      network-based water quality model: a case study of dissolved oxygen prediction.
AB  - This paper presents an application of experimental design for the optimization of
      artificial neural network (ANN) for the prediction of dissolved oxygen (DO)
      content in the Danube River. The aim of this research was to obtain a more
      reliable ANN model that uses fewer monitoring records, by simultaneous
      optimization of the following model parameters: number of monitoring sites,
      number of historical monitoring data (expressed in years), and number of input
      water quality parameters used. Box-Behnken three-factor at three levels
      experimental design was applied for simultaneous spatial, temporal, and input
      variables optimization of the ANN model. The prediction of DO was performed using
      a feed-forward back-propagation neural network (BPNN), while the selection of
      most important inputs was done off-model using multi-filter approach that
      combines a chi-square ranking in the first step with a correlation-based
      elimination in the second step. The contour plots of absolute and relative error
      response surfaces were utilized to determine the optimal values of design
      factors. From the contour plots, two BPNN models that cover entire Danube flow
      through Serbia are proposed: an upstream model (BPNN-UP) that covers 8 monitoring
      sites prior to Belgrade and uses 12 inputs measured in the 7-year period and a
      downstream model (BPNN-DOWN) which covers 9 monitoring sites and uses 11 input
      parameters measured in the 6-year period. The main difference between the two
      models is that BPNN-UP utilizes inputs such as BOD, P, and PO43-, which is in
      accordance with the fact that this model covers northern part of Serbia
      (Vojvodina Autonomous Province) which is well-known for agricultural production
      and extensive use of fertilizers. Both models have shown very good agreement
      between measured and predicted DO (with R2 >= 0.86) and demonstrated that they
      can effectively forecast DO content in the Danube River.

PMID- 29349737
TI  - Teratogenic effects induced by chitosan oligosaccharide in Wistar female rat
      Rattus norvegicus.
AB  - The aim of this research is to investigate the teratogenic effects of chitosan
      oligosaccharide in Wistar female rats (Rattus norvegicus). Chitosan LD50 value
      was calculated by probit analysis. High dose, 1/10 LD50 which equal to 150 mg/kg
      body weight, and low dose, 1/30 LD50 which equal to 50 mg/kg body weight, were
      administrated orally to Wistar female rats to examine the teratogenic effect
      during organogenesis period from 6th day to 15th day of gestation. Treated and
      control rats were sacrificed and their foetuses were examined for external,
      skeletal and visceral anomalies, number and length of foetuses and their weights.
      Obtained results showed toxicity and teratogenic effects of chitosan on treated
      rats and their progenies, i.e. high fetal mortality, offspring's weight and
      length reduction, and high incidence of fetal external, skeletal and visceral
      abnormalities. This suggested that chitosan is a teratogenic compound, restricted
      to current results from orally treated Wistar rats.

PMID- 29349738
TI  - Letter to the Editor on "Chrysotile and rock wool fibers induce chromosome
      aberrations and DNA damage in V79 lung fibroblast cells".

PMID- 29349739
TI  - Enhanced reductive dechlorination of 1,1,1-trichloroethane using zero-valent iron
      biochar-carrageenan microspheres: preparation and microcosm study.
AB  - In this study, a composite remediation material for the enhanced reductive
      dechlorination (ERD) of 1,1,1-trichloroethane (1,1,1-TCA) in aqueous solution was
      prepared. This material was comprised of biochar as the carrier and adsorbent,
      and carrageenan (CG) as the embedding medium to entrap the organic carbon sources
      and zero-valent iron (ZVI). We determined the suitable biochar dosage and organic
      carbon source in the composite alongside the optimal preparation conditions.
      Furthermore, using an anaerobic microcosm study, we discussed the performance and
      possible mechanisms of the composite on 1,1,1-TCA removal in aqueous solution.
      From this, we found that the suitable dosage of biochar in water during the
      preparation of composite microspheres was 0.2% (w/v). Under this condition, the
      biochar had a strong capacity to adsorb 1,1,1-TCA with a removal efficiency of
      84.2%. Soluble starch was selected as the appropriate organic carbon source,
      because starch-microspheres show an excellent slow-release effect in water. The
      optimal preparation conditions of microspheres were identified as follows: 2% CG
      (w/v) colloidal solution, 6% CaCl2 (w/v) solution, and a 12-h curing time. After
      25-day incubation with the composite prepared under optimized conditions, the
      removal efficiency of 1,1,1-TCA was 95.68%, which was 24.69% higher than that
      observed in the microcosm with a commercial remediation material. The scanning
      electron microscopy (SEM) images show that the amounts of ZVI and soluble starch
      inside the microsphere decreased obviously, while the biochar amount remained
      about the same. This indicates that 1,1,1-TCA in aqueous solution was mainly
      removed via soluble starch-enhanced biotic reductive dechlorination and ZVI
      enhanced abiotic reductive dechlorination. The changes in microbial community
      structure demonstrate that the composite stimulated the activities of functional
      anaerobic bacteria, in particular, regarding dechlorination and fermentation
      abilities in the microcosm, therefore enhancing the anaerobic biodegradation of
      1,1,1-TCA. This study suggests that the composite, entrapping biochar, ZVI, and
      organic carbon source in CG microspheres can significantly enhance the reductive
      dechlorination of 1,1,1-TCA in aqueous solution. We anticipate this novel
      remediation material could be successfully applied to the in situ ERD remediation
      of natural groundwater mainly contaminated with 1,1,1-TCA.

PMID- 29349740
TI  - Can Cd translocation in Oryza sativa L. be attenuated by arbuscular mycorrhizal
      fungi in the presence of EDTA?
AB  - Arbuscular mycorrhizal (AM) fungi play an important role in plant tolerance of
      heavy metal contamination. In this study, a pot experiment was conducted to
      illustrate the effects of the two AM fungi species Funneliformis mosseae (Fm) and
      Rhizophagus irregularis (Ri) on plant growth of Oryza sativa L. either with or
      without ethylenediamine tetraacetate (EDTA) addition and during exposure to five
      Cd concentrations (in the range of 0-5 mg kg-1). The results showed that Fm
      inoculation achieved greater mycorrhizal colonization and mycorrhizal dependency
      indexes than Ri inoculation. In addition, the effects of AM fungi on Cd
      biosorption and translocation in rice were also investigated in the presence of
      EDTA. Despite cooperative adsorption, the Freundlich isotherm could describe the
      biosorption effects of Cd on rice roots regardless of AM fungi inoculation or
      EDTA addition. Cd concentrations in mycorrhizal roots increased but decreased in
      mycorrhizal shoots in contrast to the control treatment. Although EDTA addition
      negatively inhibited the uptake of Cd to mycorrhizal shoots, lower translocation
      factor (TF) and bioconcentration factor (BCF) were still observed in treatments
      with EDTA compared to control treatment. Our findings suggest that Ri and Fm
      inoculation enhanced Cd immobilization in the roots, thus preventing Cd entry
      into the food chain during exposure to low and high Cd stress, respectively.

PMID- 29349741
TI  - Degradation behavior of triclosan by co-exposure to chlorine dioxide and UV
      irradiation: influencing factors and toxicity changes.
AB  - This study investigated the transformation of triclosan (TCS) following co
      exposure to UV irradiation and ClO2. Special attention was given to understand
      the influencing of water quality parameters and toxicity changes during the co
      exposure process. The results show that the co-exposure process prompted TCS
      elimination quickly and effectively, with more than 99% of TCS degraded under the
      experimental conditions. The molar yield ratios of 2,4-dichlorophenol/TCS (2,4
      DCP/TCS) were calculated to be 35.81-74.49%; however, the by-product of 2,8
      dichlorodibenzop-dioxin (2,8-Cl2DD) was not detected. The TCS degradation was
      sensitive to ClO2 dosage, pH, H2O2, and natural organic matter (NOM), but not to
      the carbonate (CO32-) concentration. Neutral and slightly alkaline condition were
      favorable to TCS elimination. The TCS removal rate increased from 85.33 to 99.75%
      when the ClO2 concentration increased from 0.25 to 1.5 mg L-1. TCS degradation
      can be promoted at low NOM level (1, 3, and 5 mg L-1), whereas was inhibited at
      high NOM concentrations of 7 and 9 mg L-1. While adding H2O2, the degradation
      rate of TCS increased with increasing H2O2 concentration from 1 to 3 mg L-1;
      however, too low or overdosed H2O2 (0.5 and 5 mg L-1) hindered TCS degradation.
      Based on the results of a microtox bioassay, the toxicity did not change
      following the co-exposure process.

PMID- 29349742
TI  - Treatment of persistent organic pollutants in wastewater using hydrodynamic
      cavitation in synergy with advanced oxidation process.
AB  - Persistent organic pollutants (POPs) are very tenacious wastewater contaminants.
      The consequences of their existence have been acknowledged for negatively
      affecting the ecosystem with specific impact upon endocrine disruption and
      hormonal diseases in humans. Their recalcitrance and circumvention of nearly all
      the known wastewater treatment procedures are also well documented. The reported
      successes of POPs treatment using various advanced technologies are not without
      setbacks such as low degradation efficiency, generation of toxic intermediates,
      massive sludge production, and high energy expenditure and operational cost.
      However, advanced oxidation processes (AOPs) have recently recorded successes in
      the treatment of POPs in wastewater. AOPs are technologies which involve the
      generation of OH radicals for the purpose of oxidising recalcitrant organic
      contaminants to their inert end products. This review provides information on the
      existence of POPs and their effects on humans. Besides, the merits and demerits
      of various advanced treatment technologies as well as the synergistic efficiency
      of combined AOPs in the treatment of wastewater containing POPs was reported. A
      concise review of recently published studies on successful treatment of POPs in
      wastewater using hydrodynamic cavitation technology in combination with other
      advanced oxidation processes is presented with the highlight of direction for
      future research focus.

PMID- 29349743
TI  - Chemically and size-resolved particulate matter dry deposition on stone and
      surrogate surfaces inside and outside the low emission zone of Milan: application
      of a newly developed "Deposition Box".
AB  - The collection of atmospheric particles on not-filtering substrates via dry
      deposition, and the subsequent study of the particle-induced material decay, is
      trivial due to the high number of variables simultaneously acting on the
      investigated surface. This work reports seasonally resolved data of chemical
      composition and size distribution of particulate matter deposed on stone and
      surrogate surfaces obtained using a new method, especially developed at this
      purpose. A "Deposition Box" was designed allowing the particulate matter dry
      deposition to occur selectively removing, at the same time, variables that can
      mask the effect of airborne particles on material decay. A pitched roof avoided
      rainfall and wind variability; a standardised gentle air exchange rate ensured a
      continuous "sampling" of ambient air leaving unchanged the sampled particle size
      distribution and, at the same time, leaving quite calm condition inside the box,
      allowing the deposition to occur. Thus, the "Deposition Box" represents an
      affordable tool that can be used complementary to traditional exposure systems.
      With this system, several exposure campaigns, involving investigated stone
      materials (ISMs) (Carrara Marble, Botticino limestone, Noto calcarenite and
      Granite) and surrogate (Quartz, PTFE, and Aluminium) substrates, have been
      performed in two different sites placed in Milan (Italy) inside and outside the
      low emission zone. Deposition rates (30-90 MUg cm-2 month-1) showed significant
      differences between sites and seasons, becoming less evident considering long
      period exposures due to a positive feedback on the deposition induced by the
      deposited particles. Similarly, different stone substrates influenced the
      deposition rates too. The collected deposits have been observed with optical and
      scanning electron microscopes and analysed by ion chromatography. Ion deposition
      rates were similar in the two sites during winter, whereas it was greater outside
      the low emission zone during summer and considering the long-period exposure. The
      dimensional distribution of the collected deposits showed a significant presence
      of fine particles in agreement with deposition rate of the ionic fraction. The
      obtained results allowed to point out the role of the fine particles fraction and
      the importance of making seasonal studies.

PMID- 29349746
TI  - A Tribute to Professor Satimaru Seno.

PMID- 29349744
TI  - Alleviation of iron toxicity in Schinus terebinthifolius Raddi (Anacardiaceae) by
      humic substances.
AB  - One of the industrial pillars of Espirito Santo state, South East of Brazil, is
      iron-mining products processing. This activity brings to a high level of coastal
      pollution due to deposition of iron particulate on fragile ecosystems as
      mangroves and restinga. Schinus therebinthifolius (aroeira) is a widespread
      restinga species. This work tested iron toxicity alleviation by vermicompost
      humic substances (HS) added to aroeira seedlings in hydroponic conditions.
      Catalase, peroxidase, and ascorbate peroxidase are antioxidant enzymes that work
      as reactive oxygen species (ROS) scavengers: they increase their activity as an
      answer to ROS concentration rise that is the consequence of metal accumulation or
      humic substance stimulation. S. terebinthifolius seedlings treated with HS and Fe
      augmented their antioxidant enzyme activities significantly less than seedlings
      treated separately with HS and Fe; their significantly lower Fe accumulation and
      the slight increase of root and leaf area confirm the biostimulating effect of HS
      and their role in blocking Fe excess outside the roots. The use of HS can be
      useful for the recovery of areas contaminated by heavy metals.

PMID- 29349747
TI  - A Tribute to the Memory of Hisamaru Hirai, MD, PhD Professor of the Department of
      Hematology and Oncology Graduate School of Medicine, The University of Tokyo.

PMID- 29349749
TI  - Thrombosis and Thromboembolism.

PMID- 29349750
TI  - In Memoriam.

PMID- 29349751
TI  - Myelodysplastic Syndromes and Secondary Acute Myelogeneous Leukemia: Directions
      for the New Millennium.

PMID- 29349752
TI  - Tumor Angiogenesis and Microcirculation.

PMID- 29349753
TI  - Expensive care? Resource-based thresholds for potentially inappropriate treatment
      in intensive care.
AB  - In intensive care, disputes sometimes arise when patients or surrogates strongly
      desire treatment, yet health professionals regard it as potentially
      inappropriate. While professional guidelines confirm that physicians are not
      always obliged to provide requested treatment, determining when treatment would
      be inappropriate is extremely challenging. One potential reason for refusing to
      provide a desired and potentially beneficial treatment is because (within the
      setting of limited resources) this would harm other patients. Elsewhere in public
      health systems, cost effectiveness analysis is sometimes used to decide between
      different priorities for funding. In this paper, we explore whether cost
      effectiveness could be used to determine the appropriateness of providing
      intensive care. We explore a set of treatment thresholds: the probability
      threshold (a minimum probability of survival for providing treatment), the cost
      threshold (a maximum cost of treatment), the duration threshold (the maximum
      duration of intensive care), and the quality threshold (a minimum quality of
      life). One common objection to cost-effectiveness analysis is that it might lead
      to rationing of life-saving treatment. The analysis in this paper might be used
      to inform debate about the implications of applying cost-effectiveness thresholds
      to clinical decisions around potentially inappropriate treatment.

PMID- 29349754
TI  - Strategies to Maintain Fertility in Young Breast Cancer Patients.
AB  - Breast cancer is the most frequently occurring cancer in women of reproductive
      age. Treatments for breast cancer may eliminate or diminish fertility, making
      discussions about fertility preservation essential prior to initiation of
      gonadotoxic therapies. Additionally, even in patients who do not require
      chemotherapy, the use of adjuvant endocrine therapy will often push patients out
      of the reproductive window before treatment is completed. The only established
      methods for fertility preservation are oocyte or embryo cryopreservation, but
      experimental methods, such as ovarian suppression with GnRH agonists and ovarian
      tissue cryopreservation, show great promise. Early referral to a fertility
      specialist for interested patients affords patients the most fertility
      preservation options, with only minimal delay to cancer treatment.

PMID- 29349755
TI  - Adjuvant Endocrine Therapy.
AB  - The use of hormonal therapy in breast cancer has improved the overall outcome for
      patients with early-stage hormone receptor-positive disease. The choice of
      hormone therapy is related to multiple factors, including menopausal state,
      patient preference, and potential side effects. Molecular profiling has allowed
      therapy to be tailored for an individual patient to some extent. However, further
      molecular studies are needed to individualize the choice and length of adjuvant
      hormone therapy. Ongoing studies are evaluating the role of additional targeted
      therapies, such as CDK4/6 inhibitors, to further improve outcome for patients
      with early-stage hormone receptor-positive breast cancer.

PMID- 29349756
TI  - Breast Cancer Screening: The Debate that Never Ends.
AB  - Screening mammography has been shown to decrease breast cancer deaths through
      randomized controlled trials. However, there remains significant debate
      surrounding the most appropriate time to commence screening and the optimal
      screening interval. Several national organizations have recently updated their
      guidelines by reanalyzing the published data. Interestingly, each organization
      has come to different conclusions regarding their recommendation for breast
      cancer screening in the average risk woman. Three of the main organizations that
      issue guidelines for breast cancer screening in the United States are reviewd in
      this chapter.

PMID- 29349757
TI  - Management of the Axilla in Early Breast Cancer.
AB  - Management of the axilla in early breast cancer patients has significantly
      evolved in the last several decades. With the arrival of the sentinel lymph node
      biopsy, surgical practice for axillary staging in patients with early breast
      cancer has become gradually less invasive and formal axillary lymph node
      dissection has been confined to selected patients. Over the last two decades,
      evidence from randomized clinical trials have allowed for the de-escalation of
      axillary surgery in the management of early stage breast cancer. Advances in the
      staging and treatment of the axilla constitute a key component in determining
      initial surgical planning and therapeutic strategies in the treatment of early
      breast cancer. This chapter provides an updated review on the history, evolution,
      and current practices for axillary management in patients with early breast
      cancer, with particular attention to the surgical recommendations and
      controversial scenarios of the evolving management of the axilla.

PMID- 29349758
TI  - Is DCIS Overrated?
AB  - Ductal carcinoma in situ (DCIS), the noninvasive form of breast cancer (BC),
      comprises just over 20% of breast cancer cases diagnosed each year in the USA.
      Most patients are treated with local excision of the disease followed by whole
      breast radiation therapy. Total mastectomy is not an uncommon approach, and total
      mastectomy with a contralateral risk-reducing mastectomy has been on the rise in
      the past decade. In estrogen receptor-positive disease, patients are often
      offered endocrine ablative therapy with a selective estrogen receptor modulator
      or an aromatase inhibitor as both treatment and prevention. Local regional
      treatment options have no impact upon ultimate overall survival. Long-term
      survival rates are higher in patients with DCIS than with any other form of the
      disease. Are these strikingly high success rates a testament to effective
      treatment strategies or is there a significant subset of DCIS that was unlikely
      to ever progress to invasive ductal carcinoma? DCIS was not seen in the US prior
      to the advent of screening mammography. When compared to other countries, the USA
      has the highest utilization of screening mammography and the incidence rate of
      DCIS. Other lines of evidence include autopsy series examining the breast tissue
      of women who died of other causes, missed-diagnosis series and current
      retrospective reviews of DCIS, all align in support of the concept of DCIS as
      indolent in the majority of cases [3-14]. The evidence suggests that both patient
      and physician misconceptions about DCIS have led to overdiagnosis and over
      treatment of DCIS. Recently, a gene expression profiling tool (12 gene assay,
      Oncotype DCIS) has emerged that shows considerable promise in predicting class in
      DCIS patients.

PMID- 29349759
TI  - Readdressing the Role of Surgery of the Primary Tumor in de Novo Stage IV Breast
      Cancer.
AB  - The impressive advances in breast cancer treatment observed in recent years also
      apply to the metastatic setting, where a subset of patients with favorable
      metastatic disease enjoy long-term survival with systemic therapy. In patients
      with distant disease, the primary tumor in the breast has not classically been
      though to merit specific locoregional therapy. However, about 6% of Stage IV
      patients in the USA and up to 20% in limited resource environments present with
      synchronous distant metastases at the time of initial diagnosis. For this group,
      who have an intact primary tumor, retrospective studies suggest that local
      therapy for the primary site may be beneficial. However, these retrospective
      analyses are biased in that women receiving local therapy to the primary site
      were younger and had biologically favorable tumors and lower volume metastatic
      disease. Two completed randomized clinical trials have shown conflicting results,
      and others are ongoing. In this chapter, we discuss the results of these studies
      through the present day and summarize their conclusions and their implications
      for clinical management.

PMID- 29349760
TI  - Advancements and Personalization of Breast Cancer Treatment Strategies in
      Radiation Therapy.
AB  - Significant technologic advances in radiation treatment delivery now allow for
      more personalized delivery considerations which incorporate individual patient
      characteristics (such as tumor location and patient anatomy) and more precise
      delivery in the breast conservation or post-mastectomy setting. The combined
      advancements with other treatment modalities (i.e., systemic therapy, surgical
      management) have had direct effects on local-regional management and outcomes
      such that currently, local-regional relapses after definitive treatment for
      localized disease are now rarely experienced. Recent advances in the radiation
      therapy field have come from careful patient selection for a variety of three
      dimensional treatment delivery techniques and alternatives to conventional
      tangential radiation. These advances have been demonstrated to diminished
      acute/long-term toxicity, minimized dose to surrounding normal tissue structures
      such as the heart and lung, and ultimately result in an improvement in the
      therapeutic ratio for radiation treatment. This chapter discusses recent
      radiation innovations and appropriate patient selection for their application,
      for a more personalized approach to radiation therapy for breast cancer patients.

PMID- 29349761
TI  - Multi-gene Panel Testing in Breast Cancer Management.
AB  - Hereditary predisposition accounts for approximately 10% of all breast cancers
      and is mostly associated with germline mutations in high-penetrance genes
      encoding for proteins participating in DNA repair through homologous
      recombination (BRCA1 and BRCA2). With the advent of massive parallel next
      generation DNA sequencing, simultaneous analysis of multiple genes with a short
      turnaround time and at a low cost has become possible. The clinical validity and
      utility of multi-gene panel testing is getting better characterized as more data
      on the significance of moderate-penetrance genes are collected from large, cancer
      genetic testing studies. In this chapter, we attempt to provide a general guide
      for interpretation of panel gene testing in breast cancer and use of the
      information obtained for clinical decision-making.

PMID- 29349762
TI  - Advances in Endocrine Therapy for Postmenopausal Metastatic Breast Cancer.
AB  - A majority of breast cancers are hormone receptor (HR) positive and are
      responsive to various types of hormone manipulation. Endocrine therapy is the
      preferred first-line therapy for patients with advanced estrogen receptor (ER)
      positive, HER2-negative breast cancer who do not have symptomatic visceral
      disease. Endocrine therapy is often continued in the second- and third-line
      setting, with chemotherapy deferred until tumor becomes endocrine therapy
      refractory and/or a visceral crisis in imminent. Therapeutic options vary based
      on clinical presentation and include single-agent therapies such as tamoxifen,
      aromatase inhibitors and fulvestrant, and combination therapies options. Over the
      past few years, multiple trials have shown significant improvement in outcomes
      when endocrine therapy is combined with CDK 4/6 inhibitors or mTOR inhibitors.
      Improved efficacy comes at a cost of a modest increase in toxicity. Mechanisms of
      ER resistance have been defined leading to multiple strategies to improve
      efficacy and overcome resistance. These include the combination therapies options
      mentioned above and other novel drugs that are in development. This review will
      summarize the existing literature regarding endocrine therapy in postmenopausal
      metastatic breast cancer and outline treatment approaches in the first-line
      metastatic setting and beyond.

PMID- 29349763
TI  - Immune Checkpoint Blockade for Breast Cancer.
AB  - An effective antitumor immune response requires interaction between cells of the
      adaptive and innate immune system. Three key elements are required: generation of
      activated tumor-directed T cells, infiltration of activated T cells into the
      tumor microenvironment, and killing of tumor cells by activated T cells. Tumor
      immune evasion can occur as a result of the disruption of each of these three key
      T cell activities, resulting in three distinct cancer-immune phenotypes. The
      immune inflamed phenotype, characterized by the presence of a robust tumor immune
      infiltrate, suggests impaired activated T cell killing of tumor cells related to
      the presence of inhibitory factors. Programmed death receptor-1 (PD-1) is an
      inhibitory transmembrane protein expressed on T cells, B cells, and NK cells. The
      interaction between PD-1 and its ligands (PD-L1/L2) functions as an immune
      checkpoint against unrestrained cytotoxic T effector cell activity-it promotes
      peripheral T effector cell exhaustion and conversion of T effector cells to
      immunosuppressive T regulatory (Treg) cells. Immune checkpoint inhibitors, which
      block the PD-1/PD-L1 axis and reactivate cytotoxic T effector cell function, are
      actively being investigated for the treatment of breast cancer.

PMID- 29349765
TI  - Issues in stem cells in Asia and SNAP decisions.

PMID- 29349764
TI  - Sexual Function Post-Breast Cancer.
AB  - The consequences of estrogen deprivation and therapeutic interventions such as
      radiation, chemotherapy and surgery have a significant negative impact on libido,
      sexual arousal, orgasmic function and the ability to have pleasurable
      intercourse. Evaluation and treatment of female sexual dysfunction is a
      significant unmet need in the breast cancer survivor in spite of the availability
      of safe and effective treatments.

PMID- 29349766
TI  - Constant existence of the sensory branch of the nerve to the pyramidalis
      distributing to the upper margin of the pubic ramus.
AB  - Twenty-one sides of 11 adult Japanese cadavers were investigated, and 2 of 21
      sides exhibited absence of the pyramidalis. We observed that all of the nerves to
      the pyramidalis included the sensory nerve branch, which distributed to the
      aponeurotic tissue in the upper area of the pubic ramus. To investigate the
      clinical relevance and developmental process of the pyramidalis, detailed
      innervation patterns of the pyramidalis and the lumber plexus were examined and
      compared with the case of absent pyramidalis. The nerves to the pyramidalis could
      be classified into five types by the derivative nerves and two subtypes by their
      courses associated with the funiculus spermaticus. In the cases of absent
      pyramidalis, similar sensory branches distributed close to the upper area of the
      pubic ramus. We deduced that the sensory branch extended along with the muscular
      branch to the pyramidalis after development of the pyramidalis and that only the
      sensory branch remained in cases in which the pyramidalis disappeared. The two
      subtypes might associate with descensus testis. Surgeons performing inguinal
      hernia repair using a mesh and tension-free surgical technique should preserve
      the nerves around the funiculus spermaticus to avoid diminished proprioception in
      the lower abdominal wall.

PMID- 29349768
TI  - GCN2 deficiency protects mice from denervation-induced skeletal muscle atrophy
      via inhibiting FoxO3a nuclear translocation.

PMID- 29349769
TI  - Examining Character Structure and Function Across Childhood and Adolescence.
AB  - Character strengths are an integral component of positive youth development that
      can promote flourishing. Developmental principles posit constructs become
      increasingly complex with age, yet this process has not been examined with
      character. Using a socioeconomically and ethnically diverse sample of 2,467 youth
      ages 9-19, bifactor models were estimated across elementary, middle, and high
      school-age groups to examine age differences in character structure and function.
      With successive age, a greater number of specific character strength factors were
      identified, suggesting character structure becomes more differentiated across
      adolescence. Results linking character bifactor models to indicators of positive
      functioning also supported differentiation in character function across ages.
      Findings point to the need for theoretical and empirical considerations of
      character structure and function across development.

PMID- 29349770
TI  - Retrospective audit of patients referred for further treatment following Mohs
      surgery for non-melanoma skin cancer.
AB  - BACKGROUND/OBJECTIVES: To describe the characteristics, subsequent management and
      outcomes of patients referred for further management following Mohs micrographic
      surgery (MMS) for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC).
      METHODS: Retrospective analysis of patients referred to a quaternary cancer
      centre from 2000 to 2015. RESULTS: In total, 83 lesions in 82 patients were
      referred for further management; 52 (62%) were SCC and 80 (96%) were located in
      the head and neck. Reasons for referral included high-risk disease for
      consideration for adjuvant radiotherapy (37/83, 45%), inadequate resection
      (28/83, 34%) or recurrence following previous MMS (15/83, 17%). Fewer than 40% of
      the 69 referrals received from MMS surgeons included photos or an operative
      report and diagram. There was discordance in pathology opinion in 11 (13%) of
      cases. Histopathology from MMS was reviewed in eight cases and there was
      discordance with the in-hospital pathology opinion in six of these. In-hospital
      re-excision was performed in 19 cases and in five of these the pathology report
      on the paraffin-sectioned re-excised tissue was discordant with prior MMS
      assessment. Significantly, two cases were associated with a misinterpretation of
      lymphocytic infiltrate as residual disease in patients with chronic lymphocytic
      leukaemia (CLL). CONCLUSION: This study highlights some of the challenges and
      limitations of MMS. Early referral for multidisciplinary management is
      recommended when MMS resection margins are inadequate or uncertain, especially
      for high-risk SCC. We recommend that referrals be accompanied by histological
      material, as well as a detailed report with operative photos and diagrams. CLL
      can pose an intraoperative diagnostic challenge. Discrepancies in the
      interpretation of MMS slides present an opportunity for improvement, and our
      findings support the role of ongoing quality assurance programs.

PMID- 29349771
TI  - CYP2D6 Protein Level Is the Major Contributor to Interindividual Variability in
      CYP2D6-Mediated Drug Metabolism in Healthy Human Liver Tissue.
AB  - CYP2D6 genetic polymorphisms are considered a major contributor to the large
      interindividual variability in CYP2D6-mediated drug metabolism, but fail to
      explain a significant portion of the variability. The aim of this study was to
      assess the ability of the CYP2D6 activity score (AS) estimated from CYP2D6
      genotype to predict CYP2D6 expression and enzyme activity. The CYP2D6 gene region
      was sequenced in 115 healthy human liver tissue samples to determine their CYP2D6
      AS. Additionally, CYP2D6 enzyme activity, protein, and mRNA levels were
      estimated. CYP2D6 AS explained 23% of the interindividual variability in CYP2D6
      activity, but only 7.5% in tissues assigned AS 1-2. The CYP2D6 protein level was
      found to be the major determinant of CYP2D6 activity, explaining 59% of
      variability. These findings suggest that while CYP2D6 AS is a good predictor of
      poor metabolizer phenotype, additional nongenetic factors may govern the rate of
      CYP2D6-mediated metabolism in those without the poor metabolizer phenotype.

PMID- 29349772
TI  - Does the Use of Diagnostic Technology Reduce Fetal Mortality?
AB  - OBJECTIVE: To examine the effect that the introduction of new diagnostic
      technology in obstetric care has had on fetal death. DATA SOURCE: The Medical
      Birth Registry of Norway provided detailed medical information for approximately
      1.2 million deliveries from 1967 to 1995. Information about diagnostic technology
      was collected directly from the maternity units, using a questionnaire. STUDY
      DESIGN: The data were analyzed using a hospital fixed-effects regression with
      fetal mortality as the outcome measure. The key independent variables were the
      introduction of ultrasound and electronic fetal monitoring at each maternity
      ward. Hospital-specific trends and risk factors of the mother were included as
      control variables. The richness of the data allowed us to perform several
      robustness tests. PRINCIPAL FINDING: The introduction of ultrasound caused a
      significant drop in fetal mortality rate, while the introduction of electronic
      fetal monitoring had no effect on the rate. In the population as a whole,
      ultrasound contributed to a reduction in fetal deaths of nearly 20 percent. For
      post-term deliveries, the reduction was well over 50 percent. CONCLUSION: The
      introduction of ultrasound made a major contribution to the decline in fetal
      mortality at the end of the last century.

PMID- 29349773
TI  - Progestin-only and combined oral contraceptives and receptor-defined
      premenopausal breast cancer risk: The Norwegian Women and Cancer Study.
AB  - Receptor-defined subtypes of breast cancer represent distinct cancer types and
      have differences in risk factors. Whether the two main hormonal forms of oral
      contraceptives (OCs); i.e. progestin-only (POC) and combined oral contraceptives
      (COC), are differentially associated with these subtypes are not well known. The
      aim of our study was to assess the effect of POC and COC use on hormone receptor
      defined breast cancer risk in premenopausal women in a prospective population
      based cohort - The Norwegian Women and Cancer Study (NOWAC). Information on OC
      use was collected from 74,862 premenopausal women at baseline. Updated
      information was applied when follow-up information became available. Multiple
      imputation was performed to handle missing data, and multivariable Cox regression
      models were used to calculate hazard ratios (HR) for breast cancer. 1,245
      incident invasive breast cancer cases occurred. POC use >=5 years was associated
      with ER+ (HR = 1.59, 95% CI 1.09- 2.32, ptrend  = 0.03) and ER+/PR+ cancer (HR =
      1.63, 95% CI 1.07-2.48, ptrend  = 0.05), and was not associated with ER-
      (pheterogeneity  = 0.36) or ER-/PR- (pheterogeneity  = 0.49) cancer. COC use was
      associated with ER- and ER-/PR- cancer, but did not increase risk of ER+ and
      ER+/PR+ cancer. Current COC use gave different estimates for ER/PR-defined
      subtypes (pheterogeneity  = 0.04). This is the first study to show significant
      associations between POC use and hormone receptor-positive breast cancer. The
      lack of power to distinguish effects of POC use on subtype development calls for
      the need of larger studies to confirm our finding.

PMID- 29349774
TI  - The vaccine adjuvant alum promotes IL-10 production that suppresses Th1
      responses.
AB  - The effectiveness of many vaccines licensed for clinical use relates to the
      induction of neutralising antibodies, facilitated by the inclusion of vaccine
      adjuvants, particularly alum. However, the ability of alum to preferentially
      promote humoral rather than cellular, particularly Th1-type responses, is not
      well understood. We demonstrate that alum activates immunosuppressive mechanisms
      following vaccination, which limit its capacity to induce Th1 responses. One of
      the key cytokines limiting excessive immune responses is IL-10. Injection of alum
      primed draining lymph node cells for enhanced IL-10 secretion ex vivo. Moreover,
      at the site of injection, macrophages and dendritic cells were key sources of IL
      10 expression. Alum strongly enhanced the transcription and secretion of IL-10 by
      macrophages and dendritic cells. The absence of IL-10 signalling did not
      compromise alum-induced cell infiltration into the site of injection, but
      resulted in enhanced antigen-specific Th1 responses after vaccination. In
      contrast to its decisive regulatory role in regulating Th1 responses, there was
      no significant change in antigen-specific IgG1 antibody production following
      vaccination with alum in IL-10-deficient mice. Overall, these findings indicate
      that injection of alum promotes IL-10, which can block Th1 responses and may
      explain the poor efficacy of alum as an adjuvant for inducing protective Th1
      immunity.

PMID- 29349775
TI  - The association between borderline pre-operative anaemia in women and outcomes
      after cardiac surgery: a cohort study.
AB  - Anaemia is common before cardiac surgery and is associated with increased
      morbidity and mortality. The World Health Organization (WHO) definition of
      anaemia is lower for women than for men by 10 g.l-1 , potentially putting women
      at a disadvantage compared with men with regard to pre-operative optimisation.
      Our hypothesis was that women with borderline anaemia (defined by us as
      haemoglobin concentration 120-129 g.l-1 ) would have a higher rate of red cell
      transfusion, morbidity and mortality than non-anaemic women (haemoglobin >= 130
      g.l-1 ). This retrospective observational study included all adult patients
      admitted for elective cardiac surgery from January 2013 to April 2016. During the
      study period, 1388 women underwent cardiac surgery. Pre-operatively, 333 (24%)
      had a haemoglobin level < 120 g.l-1 ; 408 (29%) 120-129 g.l-1 ; and 647 (47%) >=
      130 g.l-1 . Compared with non-anaemic women, women with borderline anaemia were
      more likely to be transfused (68.6% vs. 44.5%; RR 1.5, 95%CI 1.4-1.7; p < 0.0001)
      and were transfused with more units of red cells, mean (SD) 1.8 (2.8) vs. 1.3
      (3.0); p < 0.0001. Hospital length of stay was significantly longer in the
      borderline anaemia group compared with non-anaemic women, median (IQR [range]) 8
      (6-12 [3-45]) vs. 7 (6-11 [4-60]); p = 0.0159. Short- and long-term postoperative
      survival was comparable in both groups. Borderline anaemia is associated with
      increased red cell transfusion and prolonged hospital stay. Future research
      should address whether correction of borderline anaemia results in improved
      outcomes.

PMID- 29349776
TI  - Effect of palpable vs. impalpable cricothyroid membranes in a simulated emergency
      front-of-neck access scenario.
AB  - The Difficult Airway Society 2015 guidelines recommend and describe in detail a
      surgical cricothyroidotomy technique for the can't intubate, can't oxygenate
      (CICO) scenario, but this can be technically challenging for anaesthetists with
      no surgical training. Following a structured training session, 104 anaesthetists
      took part individually in a simulated can't intubate, can't oxygenate event using
      simulation and airway models to evaluate how well they could perform these front
      of-neck access techniques. Main outcomes measures were: ability to correctly
      perform the technical steps; procedural time; and success rate. Outcomes were
      compared between palpable and impalpable cricothyroid membrane scenarios.
      Anaesthetists' technical abilities were good, as assessed by a video analysis
      checklist score. Mean (SD) procedural time was 44 (16) s and 65 (17) s for the
      palpable and impalpable cricothyroid membrane models, respectively (p <= 0.001).
      First-pass tracheal tube placement was obtained in 103 out of the 104 palpable
      cricothyroidotomies and in 101 out of the 104 impalpable cricothyroidotomies (p =
      0.31). We conclude that anaesthetists can be trained to perform surgical front-of
      neck access to an acceptable level of competence and speed when assessed using a
      simulator.

PMID- 29349777
TI  - In-bed cycling in the ICU; patient safety and recollections with motivational
      effects.
AB  - BACKGROUND: In-bed cycling (IBC) is gaining interest for implementation in
      intensive care units. Our main objective was to explore patient recollections and
      experiences of early mobilization, including IBC. Secondly, we aimed to examine
      if IBC was safe and feasible. METHODS: Eleven participants were interviewed about
      their experiences during their critical illnesses and active mobilization in the
      intensive care unit. The interviews were analyzed thematically. Six participants
      were also monitored for physiological reactions and adverse events during IBC
      while mechanically ventilated. RESULTS: From the interviews, one main theme with
      three subthemes was identified. The main theme was: Early mobilization gave a
      direction toward normalization. The three subthemes were: (1) IBC gave a feeling
      of control over recovery early on during the critical illness (2) Early
      mobilization, including IBC, with continuous support from health care
      professionals gave a feeling of safety and hope for recovery for the patient; and
      (3) Unpleasant experiences and disorientation were felt during the critical
      illness and IBC. Furthermore, IBC did not induce large physiological changes or
      major adverse events in the participants who were monitored for feasibility and
      safety. CONCLUSIONS: Patient interviews indicated that the patients'
      participation in early mobilization with emphasis on IBC motivated them to be
      active in their recovery to regain a good level of health after their earlier
      critical illness during their intensive care stay. IBC was, in this small study,
      safe and feasible in the two participating intensive care units.

PMID- 29349778
TI  - Intrathecal baclofen therapy in children: an analysis of individualized goals.
AB  - AIM: To determine whether intrathecal baclofen (ITB) therapy improves performance
      and performance satisfaction in goal areas identified by patients' parents.
      METHOD: This study formed part of an ongoing multicentre national audit involving
      six paediatric ITB pump implant centres across Australia. The Canadian
      Occupational Performance Measure was the primary outcome measure utilized at
      baseline, 6 months, and 12 months after pump implants in paediatric patients
      receiving ITB therapy for the first time between 31st December 2009 and 31st
      December 2014. RESULTS: Twenty-five children had goals identified (mean age 11y
      1mo), 19 had a diagnosis of cerebral palsy and 22 were at Gross Motor Function
      Classification System level IV, V, or equivalent. Strong evidence for an
      improvement in goal performance (2.33, 95% CI 1.70, 2.96, p<0.001) and
      performance satisfaction scores (3.08, 95% CI 2.28, 3.88, p<0.001) were
      demonstrated at 6 months, compared to baseline. The differences were clinically
      significant and were sustained to 12 months. INTERPRETATION: ITB therapy in
      paediatric patients with hypertonia results in clinically significant
      improvements in average performance and performance satisfaction scores. WHAT
      THIS PAPER ADDS: The most commonly identified goals of parents of children
      treated with intrathecal (ITB) therapy were: improving ease of dressing,
      positioning, and transfers. ITB therapy is effective in improving performance and
      performance satisfaction in children with hypertonia. Score improvements are
      mainly evident within the first 6 months of therapy.

PMID- 29349779
TI  - Skeletogenesis in the Persian sturgeon Acipenser persicus and its correlation
      with gene expression of vitamin K-dependent proteins during larval development.
AB  - The present study describes morphological development of the skeleton in the
      Persian sturgeon Acipenser persicus and discusses the hypothesis that expression
      of genes encoding vitamin K-dependent proteins (VKDP) might be correlated with
      the mineralization of skeletal tissues during early development in sturgeons.
      Results showed that development of cartilage started just after hatching (mean +/
      S.D., 10.9 +/- 0.7 mm in total length, LT ) in the head and notochord, whereas
      the first signs of mineralization occurred in the dentary and in the
      dermopalatine and palatopterygoid elements of the upper jaw, coinciding with the
      onset of exogenous feeding (20.1 +/- 1.5 mm LT ). All branchial arch elements
      developed between 19.3 and 22.3 mm LT , whereas mineralization was only observed
      in tooth plates associated with the hypobranchial 1 and gill rakers at 20.8 +/-
      1.5 mm LT and 48.4 +/- 6.4 mm LT , respectively. Quantitative real-time PCR
      showed that transcripts of VKDP genes including bone Gla protein (bgp), matrix
      Gla protein (mgp) and Gla rich protein (grp) genes were significantly up
      regulated during the transition to exogenous feeding, supporting hypotheses about
      relevance of the above-mentioned genes in chondrogenesis at early developmental
      stages. The strong mineralization of skeletal elements from 21.5 to 27.3 mm LT
      (20 days post hatch) was in accordance with the maximal levels of bgp, mgp and
      grp expression indicating a correlation between development of the skeleton and
      the expression of VKDP genes. These data are important for evaluating A. persicus
      larval quality, understanding the influence of rearing biotic and abiotic factors
      on skeletogenesis and recognizing the occurrence of skeletal deformities in this
      species.

PMID- 29349780
TI  - Protective Effect of BLED-exposed Conditioned Media on Cell Injury.
AB  - Previous studies have reported that 450 nm blue light emitting diode (BLED)
      induces apoptosis through a mitochondria-mediated pathway in cancer cells and
      reduces the early stage tumor growth. This study was performed to determine the
      effects of BLED-irradiated cell metabolites on cell injury. Our results showed
      that conditioned medium (CM) from cells irradiated with low-dose BLED (LCM)
      inhibited apoptosis and increased cell survival. Cell protection-related proteins
      were identified in cell metabolites of CM and LCM using 2-DE and MALDI-TOF
      analysis. Treatment with LCM inhibited apoptotic cell death and increased the
      live cell population. The cellular protective effect of LCM was associated with
      keratin and collagen type VI secretion from cells after low dose of BLED
      irradiation. Interestingly, expression of endoplasmic reticulum stress proteins
      was dose dependently increased after 4 h BLED irradiation. Only levels of BiP,
      CHOP and ERO1-Lalpha were decreased significantly after 24 h incubation,
      indicating their anti-apoptotic property in these cells. These results indicated
      that cell metabolites stimulated by low-dose BLED irradiation have a
      cytoprotective effect on cell injury via increasing transient intracellular ER
      stress. Further studies remain to provide the molecular mechanisms of LCM for
      cytoprotective activity.

PMID- 29349781
TI  - Mirror neurons and intention understanding: Dissociating the contribution of
      object type and intention to mirror responses using electromyography.
AB  - Since their discovery in the monkey and human brain, mirror neurons have been
      claimed to play a key role in understanding others' intentions. For example,
      "action-constrained" mirror neurons in inferior parietal lobule fire when the
      monkey observes a grasping movement that is followed by an eating action, but not
      when it is followed by a placing action. It is claimed these responses enable the
      monkey to predict the intentions of the actor. These findings have been
      replicated in human observers by recording electromyography responses of the
      mouth-opening mylohyoid muscle during action observation. Mylohyoid muscle
      activity was greater during the observation of actions performed with the
      intention to eat than of actions performed with the intention to place, again
      suggesting an ability to predict the actor's intentions. However, in previous
      studies, intention was confounded with object type (food for eating actions,
      nonfood for placing actions). We therefore used electromyography to measure
      mylohyoid activity in participants observing eating and placing actions. Unlike
      previous studies, we used a design in which each object (food, nonfood) could be
      both eaten and placed, and thus participants could not predict the actor's
      intention at the onset of the action. Greater mylohyoid activity was found for
      the observation of actions performed on food objects, irrespective of intention,
      indicating that the object type, not the actor's intention, drives the mirror
      response. This result suggests that observers' motor responses during action
      observation reflect the presence of a particular object, rather than the actor's
      underlying intentions.

PMID- 29349782
TI  - New species of the genus Spectracanthicus (Loricariidae, Hypostominae,
      Ancistrini) from the Rio Javaes (Rio Araguaia basin), with a description of gross
      brain morphology.
AB  - A new species of Spectracanthicus is described from the Rio Javaes, Rio Araguaia
      basin. The new species is distinguished from its congeners (except
      Spectracanthicus immaculatus) by colour pattern: body dark grey to dark brown
      without dots or blotches (v. body colour with yellowish small dots in
      Spectracanthicus murinus, Spectracanthicus punctatissimus and Spectracanthicus
      tocantinensis and large white dots in Spectracanthicus zuanoni). It can be
      further distinguished from S. immaculatus by having thicker and less numerous
      teeth, with up to eight premaxillary and 20 dentary teeth (v. teeth thinner and
      more numerous with up to 22 premaxillary and 30 dentary teeth); dorsal and caudal
      fins without curved spines (v. dorsal and caudal fins with curved spines). Other
      osteological characters can also diagnose the new species from its congeners. In
      addition, a gross brain description and brief comments on the new species'
      ecological habitat are given.

PMID- 29349783
TI  - Development of Cotton Fabrics with Durable UV Protective and Self-cleaning
      Property by Deposition of Low TiO2 Levels through Sol-gel Process.
AB  - In this article, the deposition of TiO2 on cotton fabric using sol-gel technique
      has been described. Various process routes (pad-dry-cure, pad-dry-hydrothermal
      and pad-dry-solvothermal) were examined to impart a stable coating of TiO2 on
      fabric. The role of precursor concentration, process temperature and time of
      treatment were studied to aim at a wash durable, UV protective and self-cleaning
      property in the treated fabric. EDX and ICP-MS techniques were used to examine
      the add-on percentage of TiO2 on cotton fabrics treated via different routes. It
      has been found that the TiO2 remains largely amorphous and nondurable if it is
      given a short thermal treatment. To convert the deposited TiO2 to its anatase
      crystal form, a prolonged hydrothermal treatment for at least 3 h needs to be
      given. TiO2 deposition levels of less than 0.1% were found to be effective in
      imparting reasonable degree of UV protection and self-cleaning property to the
      cotton fabric. The self-cleaning ability of the treated fabric against coffee
      stain was also studied and was found to be related to the process route and the
      deposition levels of TiO2 .

PMID- 29349784
TI  - Magnetic molecularly imprinted polymers based on silica modified by deep eutectic
      solvents for the rapid simultaneous magnetic-based solid-phase extraction of
      Salvia miltiorrhiza bunge, Glycine max (Linn.) Merr and green tea.
AB  - Novel magnetic molecularly imprinted polymers (MMIPs) with multiple-template
      based on silica were modified by four types of deep eutectic solvents (DESs) for
      the rapid simultaneous magnetic solid-phase extraction (MSPE) of tanshinone I,
      tanshinone IIA, and cryptotanshinone from Salvia miltiorrhiza bunge; glycitein,
      genistein, and daidzein from Glycine max (Linn.) Merr; and epicatechin,
      epigallocatechin gallate, and epicatechin gallate from green tea, respectively.
      The synthesized materials were characterized by Fourier transform infrared
      spectroscopy and field emission scanning electron microscopy. Single factor
      experiments were to explore the relationship between the extraction efficiency
      and four factors (the sample solution pH, amount of DESs for modification, amount
      of adsorbent, and extraction time). It was showed that the DES4-MMIPs have better
      extraction ability than the MMIPs without DESs and the other three DESs-modified
      MMIPs. The best extraction recoveries with DES4-MMIP were tanshinone I (85.57%),
      tanshinone IIA (80.58%), cryptotanshinone (92.12%), glycitein (81.65%), genistein
      (87.72%), daidzein (92.24%), epicatechin (86.43%), epigallocatechin gallate
      (80.92%), and epicatechin gallate (93.64%), respectively. The novel multiple
      template MMIPs materials modified by DES for the rapid simultaneous MSPE of
      active compounds were proved to reduce the experimental steps than single
      template technique, and increase the extraction efficiency.

PMID- 29349785
TI  - A novel MLPH variant in dogs with coat colour dilution.
AB  - Coat colour dilution may be the result of altered melanosome transport in
      melanocytes. Loss-of-function variants in the melanophilin gene (MLPH) cause a
      recessively inherited form of coat colour dilution in many mammalian and avian
      species including the dog. MLPH corresponds to the D locus in many domestic
      animals, and recessive alleles at this locus are frequently denoted with d. In
      this study, we investigated dilute coloured Chow Chows whose coat colour could
      not be explained by their genotype at the previously known MLPH:c.-22G>A variant.
      Whole genome sequencing of such a dilute Chow Chow revealed another variant in
      the MLPH gene: MLPH:c.705G>C. We propose to designate the corresponding mutant
      alleles at these two variants d1 and d2 . We performed an association study in a
      cohort of 15 dilute and 28 non-dilute Chow Chows. The dilute dogs were all either
      compound heterozygous d1 /d2 or homozygous d2 /d2 , whereas the non-dilute dogs
      carried at least one wildtype allele D. The d2 allele did not occur in 417 dogs
      from diverse other breeds. However, when we genotyped a Sloughi family, in which
      a dilute coloured puppy had been born out of non-dilute parents, we again
      observed perfect co-segregation of the newly discovered d2 allele with coat
      colour dilution. Finally, we identified a blue Thai Ridgeback with the d1 /d2
      genotype. Thus, our data identify the MLPH:c.705G>C as a variant explaining a
      second canine dilution allele. Although relatively rare overall, this d2 allele
      is segregating in at least three dog breeds, Chow Chows, Sloughis and Thai
      Ridgebacks.

PMID- 29349786
TI  - Acute lion's mane jellyfish, Cyanea capillata (Cnideria: Scyphozoa), exposure to
      Atlantic salmon (Salmo salar L.).
AB  - Jellyfish-induced gill pathology relies upon occasional diagnostic observations
      yet the extent and impact of jellyfish blooms on aquaculture may be significant.
      Idiopathic gill lesions are often observed in apparently healthy fish. This study
      exposed Atlantic salmon (Salmo salar L.) smolts to macerated Cyanea capillata at
      2.5 and 5 g/L for 2 hr under controlled laboratory conditions. Blood chemistry
      and gill histopathology were examined over a subsequent 4-week period. Fish
      showed an acute response to the presence of jellyfish, including characteristic
      external "whiplash" discoloration of the skin and acute increases in blood
      electrolytes and CO2 concentration; however, these were resolved within 4 days
      after exposure. Histopathologically, gills showed first an acute oedema with
      epithelial separation followed by focal haemorrhage and thrombus formation, and
      then progressive inflammatory epithelial hyperplasia that progressively resolved
      over the 4 weeks post-exposure. Results were consistent with the envenomation of
      gills with cytotoxic neurotoxins and haemolysins known to be produced by C.
      capillata. This study suggests that many focal hyperplastic lesions on gills,
      especially those involving focal thrombi, may be the result of jellyfish stings.
      Thus, the presence of jellyfish and their impact may be severe and understated in
      terms of marine fish aquaculture and fish welfare.

PMID- 29349787
TI  - Treatment of lumpfish (Cyclopterus lumpus L.) infected with Gyrodactylus
      cyclopteri (Scyborskaya 1948).

PMID- 29349788
TI  - Roles of water quality and disinfectant application on inactivation of fish
      pathogenic Streptococcus agalactiae with povidone iodine, quaternary ammonium
      compounds and glutaraldehyde.
AB  - Streptococcosis is an important bacterial disease in Nile tilapia causing severe
      economic losses to tilapia aquaculture worldwide. The effects of water quality
      (low- [LS] and high-level [HS] soiling, to mimic clean or dirty surface
      conditions and temperatures) and disinfectant application (diluted concentrations
      and exposure time) were characterized on the inactivation of Streptococcus
      agalactiae isolated from diseased tilapia. Five isolates were tested against
      three commercial disinfectant products with the main ingredients being povidone
      iodine (Anidine 100TM; AD), benzalkonium chloride (Better BKC 80%TM; BKC 80), and
      a mixture of quaternary ammonium compounds and glutaraldehyde (ChloraldehydeTM;
      CR). CR demonstrated highest efficacy to S. agalactiae inactivation, followed by
      BKC 80 and AD, respectively. Higher-level soiling, low temperature, diluted
      concentrations and short exposure time all decreased the disinfectant efficacy.
      CR and BKC 80 provided more than 5-log inactivation at 1-min exposure at 20
      degrees C under HS conditions, and also with ten-fold-diluted concentrations at
      60-min exposure time at 30 degrees C. However, AD required 10-min exposure to
      effectively remove bacteria under LS conditions at 30 degrees C. The results
      could facilitate aquaculture management planning that leads to operating cost
      reductions and improvements in biosecurity.

PMID- 29349789
TI  - Postmarketing cases of eluxadoline-associated pancreatitis in patients with or
      without a gallbladder.
AB  - BACKGROUND: Cases of pancreatitis were identified in the eluxadoline clinical
      development program, reflected in initial product labelling, and the subject of
      postmarketing reports. AIM: To analyse postmarketing cases of eluxadoline
      associated pancreatitis. METHODS: We retrospectively analysed all US adverse
      event reports of pancreatitis associated with eluxadoline reported to the FDA
      Adverse Event Reporting System (FAERS) database from May 27, 2015 through
      February 15, 2017. RESULTS: The analysis included 119 cases of pancreatitis
      associated with eluxadoline; one resulted in death and 75 in hospitalisation.
      Sixty-seven cases reported the presence (n = 12) or absence (n = 55) of the
      patient's gallbladder. The eluxadoline dose received in the 55 cases of patients
      without gallbladders was 75 mg (n = 43), 100 mg (n = 5), or not reported (n = 7).
      Of the 119 cases, 37 reported the patient did not abuse alcohol and 82 did not
      report the alcohol abuse status. The single fatal case occurred in a patient
      without a gallbladder who received eluxadoline 75 mg and did not abuse alcohol.
      Forty-seven cases reported development of pancreatitis within the first or second
      dose of eluxadoline initiation. The median time to onset for the development of
      pancreatitis (n = 83) was 1 day, ranging from 1 to 56 days of continued use of
      eluxadoline. CONCLUSION: The FAERS cases suggest that patients with or without a
      gallbladder receiving eluxadoline are at risk for the development of
      pancreatitis. However, patients without a gallbladder, despite receiving the
      recommended lower dose of eluxadoline 75 mg and screening for alcohol abuse,
      appear to be overrepresented among patients who developed eluxadoline-associated
      pancreatitis.

PMID- 29349790
TI  - Identification of the absorbed components and metabolites of modified Huo Luo
      Xiao Ling Dan in rat plasma by UHPLC-Q-TOF/MS/MS.
AB  - To reveal the material basis of Huo Luo Xiao Ling Dan (HLXLD), a sensitive and
      selective ultra-high performance liquid chromatography coupled with quadrupole
      time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) method was developed to
      identify the absorbed components and metabolites in rat plasma after oral
      administration of HLXLD. The plasma samples were pretreated by liquid-liquid
      extraction and separated on a Shim-pack XR-ODS C18 column (75 * 3.0 mm, 2.2 MUm)
      using a gradient elution program. With the optimized conditions and single sample
      injection of each positive or negative ion mode, a total of 109 compounds,
      including 78 prototype compounds and 31 metabolites, were identified or
      tentatively characterized. The fragmentation patterns of representative compounds
      were illustrated as well. The results indicated that aromatization and hydration
      were the main metabolic pathways of lactones and tanshinone-related metabolites;
      demethylation and oxidation were the major metabolic pathways of alkaloid-related
      compounds; methylation and sulfation were the main metabolic pathways of phenolic
      acid-related metabolites. It is concluded the developed UHPLC-Q-TOF/MS method
      with high sensitivity and resolution is suitable for identifying and
      characterizing the absorbed components and metabolites of HLXLD, and the results
      will provide essential data for further studying the relationship between the
      chemical components and pharmacological activity of HLXLD.

PMID- 29349791
TI  - Predicting patterns of change and stability in student performance across a
      medical degree.
AB  - CONTEXT: Evidence of predictive validity is essential for making robust selection
      decisions in high-stakes contexts such as medical student selection. Currently
      available evidence is limited to the prediction of academic performance at single
      points in time with little understanding of the factors that might undermine the
      predictive validity of tests of academic and non-academic qualities considered
      important for success. This study addressed these issues by predicting students'
      changing performance across a medical degree and assessing whether factors
      outside an institution's control (such as the uptake of commercial coaching)
      impact validity. METHODS: Three cohorts of students (n = 301) enrolled in an
      undergraduate medical degree from 2007-2013 were used to identify trajectories of
      student academic performance using growth mixture modelling. Multinomial logistic
      regression assessed whether past academic performance, a test of cognitive
      ability and a multiple mini-interview could predict a student's likely trajectory
      and whether this predictive validity was different for those who undertook
      commercial coaching compared with those who didn't. RESULTS: Among the medical
      students who successfully graduated (n = 268), four unique trajectories of
      academic performance were identified. In three trajectories, performance changed
      at the time when learning became more self-directed and focused on clinical
      specialties. Scores on all selection tests, with the exception of a test of
      abstract reasoning, significantly affected the odds of following a trajectory
      that was consistently below average. However, selection tests could not
      distinguish those whose performance improved across time from those whose
      performance declined after an average start. Commercial coaching increased the
      odds of being among the below-average performers, but did not alter the
      predictive validity of the selection tests. CONCLUSION: Identifying distinct
      groups of students has important implications for selection, but also for
      educating medical students. Commercial coaching may result in selecting students
      who are less suited for coping with the rigours of medical studies.

PMID- 29349792
TI  - Meta-analysis of Gaussian individual patient data: Two-stage or not two-stage?
AB  - Quantitative evidence synthesis through meta-analysis is central to evidence
      based medicine. For well-documented reasons, the meta-analysis of individual
      patient data is held in higher regard than aggregate data. With access to
      individual patient data, the analysis is not restricted to a "two-stage" approach
      (combining estimates and standard errors) but can estimate parameters of interest
      by fitting a single model to all of the data, a so-called "one-stage" analysis.
      There has been debate about the merits of one- and two-stage analysis. Arguments
      for one-stage analysis have typically noted that a wider range of models can be
      fitted and overall estimates may be more precise. The two-stage side has
      emphasised that the models that can be fitted in two stages are sufficient to
      answer the relevant questions, with less scope for mistakes because there are
      fewer modelling choices to be made in the two-stage approach. For Gaussian data,
      we consider the statistical arguments for flexibility and precision in small
      sample settings. Regarding flexibility, several of the models that can be fitted
      only in one stage may not be of serious interest to most meta-analysis
      practitioners. Regarding precision, we consider fixed- and random-effects meta
      analysis and see that, for a model making certain assumptions, the number of
      stages used to fit this model is irrelevant; the precision will be approximately
      equal. Meta-analysts should choose modelling assumptions carefully. Sometimes
      relevant models can only be fitted in one stage. Otherwise, meta-analysts are
      free to use whichever procedure is most convenient to fit the identified model.

PMID- 29349793
TI  - The effectiveness and safety of ledipasvir plus sofosbuvir in adolescents with
      chronic hepatitis C virus genotype 4 infection: a real-world experience.
AB  - BACKGROUND: The combination of ledipasvir plus sofosbuvir was recently approved
      for treatment of adolescent (12-17 years) HCV genotype 1, 4, 5 & 6 patients.
      However, few clinical trials have been performed in genotype 1 patients. AIM: To
      investigate the effectiveness and safety of ledipasvir plus sofosbuvir in chronic
      HCV adolescent patients with genotype 4 in the real world. METHODS: This
      prospective multicentre (six centres) open-label study included 144 adolescent
      chronic HCV patients with genotype 4 (mean age 14 +/- 2, 69% males). All patients
      received a combination tablet containing 400 mg sofosbuvir and 90 mg ledipasvir
      once daily for 12 weeks. Laboratory and virological markers were evaluated at
      baseline, week 4, week 8 and week 12 (EOT), and 12 weeks after end of treatment
      (SVR12). RESULTS: SVR12 was observed in 142/144 patients (99%). The relapsers
      occurred in previous naive patients (n = 2/128, 2%), while the experienced
      patients showed 100% SVR12. SVR12 was 98% in F0/F1 patients in comparison to 100%
      in F2 patients (P = 0.552). No serious side effects were observed, nor was
      treatment discontinuation or death. Headache was the most common side effect in
      all patients (20%). In experienced patients, pruritus (31%, P = 0.007), diarrhoea
      (44%, P < 0.001) and skin rash (19%, P = 0.002) were higher than in naive
      patients. CONCLUSIONS: A ledipasvir plus sofosbuvir regimen is well tolerated and
      effective, and can be used safely in treating adolescent patients with chronic
      hepatitis C genotype 4.

PMID- 29349794
TI  - Adolescents' Reward-related Neural Activation: Links to Thoughts of Nonsuicidal
      Self-Injury.
AB  - Adolescence is a critical developmental period marked by an increase in risk
      behaviors, including nonsuicidal self-injury (NSSI). Heightened reward-related
      brain activation and relatively limited recruitment of prefrontal regions
      contribute to the initiation of risky behaviors in adolescence. However, neural
      reward processing has not been examined among adolescents who are at risk for
      future engagement for NSSI specifically, but who have yet to actually engage in
      this behavior. In the current fMRI study (N = 71), we hypothesized that altered
      reward processing would be associated with adolescents' thoughts of NSSI. Results
      showed that NSSI youth exhibited heightened activation in the bilateral putamen
      in response to a monetary reward. This pattern of findings suggests that
      heightened neural sensitivity to reward is associated with thoughts of NSSI in
      early adolescence. Implications for prevention are discussed.

PMID- 29349795
TI  - Quality of life assumptions determine which cervical cancer screening strategies
      are cost-effective.
AB  - Quality-adjusted life years are used in cost-effectiveness analyses (CEAs). To
      calculate QALYs, a "utility" (0-1) is used for each health state induced or
      prevented by the intervention. We aimed to estimate the impact of quality of life
      (QoL) assumptions (utilities and durations of health states) on CEAs of cervical
      cancer screening. To do so, 12 alternative sets of utility assumptions were
      retrieved from published cervical cancer screening CEAs. Two additional sets were
      based on empirical QoL data that were integrally obtained through two different
      measures (SF-6D and EQ-5D) from eight groups of women (total n = 3,087), from
      invitation for screening to diagnosis with cervical cancer. Per utility set we
      calculated the number of quality-adjusted days lost (QADL) for each relevant
      health state in cervical cancer screening, by multiplying the study-specific
      assumed disutilities (i.e., 1-utility) with study-specific durations of the loss
      in QoL, resulting in 14 "QADL-sets." With microsimulation model MISCAN we
      calculated cost-effectiveness of 342 alternative screening programs (varying in
      primary screening test [Human Papillomavirus (HPV) vs. cytology], starting ages,
      and screening interval) for each of the 14 QADL-sets. Utilities used in CEAs
      appeared to differ largely. We found that ten QADL-sets from the literature
      resulted in HPV and two in cytology as preferred primary test. The SF-6D
      empirical QADL-set resulted in cytology and the EQ-5D one in HPV as preferred
      primary test. In conclusion, assumed utilities and health state durations
      determine cost-effectiveness of cervical cancer screening. Also, the measure used
      to empirically assess utilities can be crucial for CEA conclusions.

PMID- 29349796
TI  - Quantification of acyclovir in dermal interstitial fluid and human serum by ultra
      high-performance liquid-high-resolution tandem mass spectrometry for topical
      bioequivalence evaluation.
AB  - Time-concentration curves for the topical anti-viral drug acyclovir can provide
      valuable information for drug development. Open flow microperfusion is used for
      continuous sampling of dermal interstitial fluid but it requires validated
      methods for subsequent sample analysis. Therefore, we developed a sensitive,
      selective and high-throughput ultra-high-performance liquid chromatography-high
      resolution tandem mass spectrometry method to determine acyclovir in human dermal
      interstitial fluid and serum. We validated the method over a concentration range
      of 0.1-25 ng/mL for a sample volume of just 20 MUL and employed cation-exchange
      solid-phase extraction in a fully automated sample treatment procedure. Short-
      and long-term sample stability data and the analysis of 5000 samples from a
      clinical trial demonstrate the successful application of our method.

PMID- 29349797
TI  - Efficacy and toxicity of praziquantel in helminth-infected barbel (Barbus barbus
      L.).
AB  - This study evaluated efficacy and toxicity of the pyrazinoisoquinoline
      anthelmintic praziquantel (PZQ) in barbel infected with metacercariae of
      Diplostomum spathaceum and adult Pomphorhynchus laevis, and assessed antioxidant
      biomarkers and the lipid peroxidation response in juvenile barbel post-treatment.
      The estimated 96-hr LC50 of PZQ was 28.6 mg/L. For evaluation of efficacy, barbel
      naturally infected with D. spathaceum were exposed to a 10 and 20 mg/L PZQ 4-day
      bath treatment. Both concentrations were 100% effective against D. spathaceum and
      significantly (p < .01) affected the activity of catalase, superoxide dismutase,
      glutathione reductase and glutathione-S-transferase as well as levels of reduced
      glutathione in liver and muscle. The efficacy of orally administered PZQ was
      assessed in adult barbel naturally infected with P. laevis. Fish were
      administered 10, 30 and 50 mg/kg of body weight and examined via gut dissection
      after 6 days. The 50 mg/kg dose significantly decreased the intensity of
      infection. Praziquantel is a feasible bath treatment for barbel infected with D.
      spathaceum and has potential for oral treatment of broodfish infected with P.
      laevis.

PMID- 29349798
TI  - Small area estimation of proportions with different levels of auxiliary data.
AB  - Binary data are often of interest in many small areas of applications. The use of
      standard small area estimation methods based on linear mixed models becomes
      problematic for such data. An empirical plug-in predictor (EPP) under a unit
      level generalized linear mixed model with logit link function is often used for
      the estimation of a small area proportion. However, this EPP requires the
      availability of unit-level population information for auxiliary data that may not
      be always accessible. As a consequence, in many practical situations, this EPP
      approach cannot be applied. Based on the level of auxiliary information
      available, different small area predictors for estimation of proportions are
      proposed. Analytic and bootstrap approaches to estimating the mean squared error
      of the proposed small area predictors are also developed. Monte Carlo simulations
      based on both simulated and real data show that the proposed small area
      predictors work well for generating the small area estimates of proportions and
      represent a practical alternative to the above approach. The developed predictor
      is applied to generate estimates of the proportions of indebted farm households
      at district-level using debt investment survey data from India.

PMID- 29349799
TI  - Simultaneous LC-MS/MS bioanalysis of etoposide and paclitaxel in mouse tissues
      and plasma after oral administration of self-microemulsifying drug-delivery
      systems.
AB  - In this study, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method
      was developed and validated to simultaneously determine the anticancer drugs
      etoposide and paclitaxel in mouse plasma and tissues including liver, kidney,
      lung, heart, spleen and brain. The analytes were extracted from the matrices of
      interest by liquid-liquid extraction using methyl tert-butyl ether
      dichloromethane (1:1, v/v). Chromatographic separation was achieved on an
      Ultimate XB-C18 column (100 * 2.1 mm, 3 MUm) at 40 degrees C and the total run
      time was 4 min under a gradient elution. Ionization was conducted using
      electrospray ionization in the positive mode. Stable isotope etoposide-d3 and
      docetaxel were used as the internal standards. The lower limit of quantitation
      (LLOQ) of etoposide was 1 ng/g tissue for all tissues and 0.5 ng/mL for plasma.
      The LLOQ of paclitaxel was 0.4 ng/g tissue and 0.2 ng/mL for all tissues and
      plasma, respectively. The coefficients of correlation for all of the analytes in
      the tissues and plasma were >0.99. Both intra- and inter-day accuracy and
      precision were satisfactory. This method was successfully applied to measure
      plasma and tissue drug concentrations in mice treated with etoposide and
      paclitaxel-loaded self-microemulsifying drug-delivery systems.

PMID- 29349800
TI  - Specific cutaneous infiltrates of acute myeloid leukaemia in a venous leg ulcer:
      an unusual presentation of leukaemia cutis.

PMID- 29349801
TI  - Evaluating the effects of rater and subject factors on measures of association.
AB  - Large-scale agreement studies are becoming increasingly common in medical
      settings to gain better insight into discrepancies often observed between
      experts' classifications. Ordered categorical scales are routinely used to
      classify subjects' disease and health conditions. Summary measures such as
      Cohen's weighted kappa are popular approaches for reporting levels of association
      for pairs of raters' ordinal classifications. However, in large-scale studies
      with many raters, assessing levels of association can be challenging due to
      dependencies between many raters each grading the same sample of subjects'
      results and the ordinal nature of the ratings. Further complexities arise when
      the focus of a study is to examine the impact of rater and subject
      characteristics on levels of association. In this paper, we describe a flexible
      approach based upon the class of generalized linear mixed models to assess the
      influence of rater and subject factors on association between many raters'
      ordinal classifications. We propose novel model-based measures for large-scale
      studies to provide simple summaries of association similar to Cohen's weighted
      kappa while avoiding prevalence and marginal distribution issues that Cohen's
      weighted kappa is susceptible to. The proposed summary measures can be used to
      compare association between subgroups of subjects or raters. We demonstrate the
      use of hypothesis tests to formally determine if rater and subject factors have a
      significant influence on association, and describe approaches for evaluating the
      goodness-of-fit of the proposed model. The performance of the proposed approach
      is explored through extensive simulation studies and is applied to a recent large
      scale cancer breast cancer screening study.

PMID- 29349802
TI  - Shades of Awareness on the Mechanisms Underlying the Quality of Conscious
      Representations: A Commentary to Fazekas and Overgaard ().
AB  - Fazekas and Overgaard () present a novel, multidimensional model that explains
      different ways in which conscious representations can be degraded. Moreover, the
      authors discuss possible mechanisms that underlie different kinds of degradation,
      primarily those related to attentional processing. In this letter, we argue that
      the proposed mechanisms are not sufficient. We propose that (1) attentional
      mechanisms work differently at various processing stages; and (2) factors that
      are independent of attentional ones, such as expectation, previous experience,
      and context, should be accounted for if we are aiming to construct a
      comprehensive model of conscious visual perception.

PMID- 29349803
TI  - Assessment of mitral annulus and mitral leaflet in nonvalvular atrial
      fibrillation patients with various degrees of mitral regurgitation: Real time 3D
      transesophageal echocardiography.
AB  - AIM: To study the changes of mitral valve (MV) in patients with nonvalvular
      atrial fibrillation (NVAF)-related mitral regurgitation (MR) and the relationship
      between MV parameters and the enlarged left atrium (LA). MATERIALS AND METHODS: A
      total of 43 patients with NVAF were divided into two groups: (1) the MR1 group
      with mild MR and (2) the MR2 group with moderate-to-severe MR. Real time 3D
      transesophageal echocardiography (TEE) was performed to detect the structure of
      MV. RESULTS: There were no significant differences in the basic characteristics
      among the three groups. As compared with the control group, anterolateral to
      posteromedial diameter of the annulus (DALPm), anterior to posterior diameter
      (DAP), three-dimensional circumference (C3D), two-dimensional area (A2D), three
      dimensional area (A3D), exposed area of the leaflets (A3DE), and NPA (nonplanar
      angle) were significantly increased, whereas height and ellipticity were
      significantly decreased in the MR1 group and MR2 group. The overall longitudinal
      strain of left atrium (GLS) was significantly decreased in the MR1 and MR2 groups
      compared to the control group. Furthermore, GLS was inversely correlated with
      DALPm, DAP, C3D, A2D, A3D, A3DE, and NPA, whereas positively correlated with
      height, ellipticity, and the leaflet tenting height in both MR1 and MR2 groups.
      CONCLUSION: Even in NVAF patients with mild MR, the structure of MV was changed
      intensively with the expansion and deformation of the "saddle shape" structure.
      The deformation of MV was associated with the decreased function of LA. Our
      results may provide novel insight into evaluation risk factors leading to AF
      recurrence after ablation procedures.

PMID- 29349804
TI  - Integrity situational judgement test for medical school selection: judging 'what
      to do' versus 'what not to do'.
AB  - CONTEXT: Despite their widespread use in medical school selection, there remains
      a lack of clarity on exactly what situational judgement tests (SJTs) measure.
      OBJECTIVES: We aimed to develop an SJT that measures integrity by combining
      critical incident interviews (inductive approach) with an innovative deductive
      approach. The deductive approach guided the development of the SJT according to
      two established theoretical models, of which one was positively related to
      integrity (honesty-humility [HH]) and one was negatively related to integrity
      (cognitive distortions [CD]). The Integrity SJT covered desirable (HH-based) and
      undesirable (CD-based) response options. We examined the convergent and
      discriminant validity of the Integrity SJT and compared the validity of the HH
      based and CD-based subscores. METHODS: The Integrity SJT was administered to 402
      prospective applicants at a Dutch medical school. The Integrity SJT consisted of
      57 scenarios, each followed by four response options, of which two represented HH
      facets and two represented CD categories. Three SJT scores were computed,
      including a total, an HH-based and a CD-based score. The validity of these scores
      was examined according to their relationships with external integrity-related
      measures (convergent validity) and self-efficacy (discriminant validity).
      RESULTS: The three SJT scores correlated significantly with all integrity-related
      measures and not with self-efficacy, indicating convergent and discriminant
      validity. In addition, the CD-based SJT score correlated significantly more
      strongly than the HH-based SJT score with two of the four integrity-related
      measures. CONCLUSIONS: An SJT that assesses the ability to correctly recognise CD
      based response options as inappropriate (i.e. what one should not do) seems to
      have stronger convergent validity than an SJT that assesses the ability to
      correctly recognise HH-based response options as appropriate (i.e. what one
      should do). This finding might be explained by the larger consensus on what is
      considered inappropriate than on what is considered appropriate in a challenging
      situation. It may be promising to focus an SJT on the ability to recognise what
      one should not do.

PMID- 29349805
TI  - Hybrid Continuous-Flow Total Artificial Heart.
AB  - Clinical studies using total artificial hearts (TAHs) have demonstrated that
      pediatric and adult patients derive quality-of-life benefits from this form of
      therapy. Two clinically-approved TAHs and other pumps under development, however,
      have design challenges and limitations, including thromboembolic events,
      neurologic impairment, infection risk due to large size and percutaneous
      drivelines, and lack of ambulation, to name a few. To address these limitations,
      we are developing a hybrid-design, continuous-flow, implantable or
      extracorporeal, magnetically-levitated TAH for pediatric and adult patients with
      heart failure. This TAH has only two moving parts: an axial impeller for the
      pulmonary circulation and a centrifugal impeller for the systemic circulation.
      This device will utilize the latest generation of magnetic bearing technology.
      Initial geometries were established using pump design equations, and
      computational modeling provided insight into pump performance. The designs were
      the basis for prototype manufacturing and hydraulic testing. The study results
      demonstrate that the TAH is capable of delivering target blood flow rates of 1
      6.5 L/min with pressure rises of 1-92 mm Hg for the pulmonary circulation and 24
      150 mm Hg for the systemic circulation at 1500-10 000 rpm. This initial design of
      the TAH was successful and serves as the foundation to continue its development
      as a novel, more compact, nonthrombogenic, and effective therapeutic alternative
      for infants, children, adolescents, and adults with heart failure.

PMID- 29349806
TI  - Blue Monday Is Real for Suicide: A Case-Control Study of 188,601 Suicides.
AB  - Many studies have reported that suicides tend to occur on Mondays. However, owing
      to a lack of controls, conclusive findings on the potential effects of a day of
      the week on suicides have been lacking. We analyzed public data for causes of
      death from 1997 to 2015 in the Republic of Korea. Accidental death was used as a
      control group. The probability of suicide on each day of the week according to
      age group was calculated. A total of 377,204 deaths (188,601 suicides and 188,603
      accidental deaths) were used. The frequency of suicide was highest on Monday and
      decreased throughout the week until Saturday. Accidental death was highest on
      Saturday and showed no variations according to weekday. For people in their teens
      and 20s, the probabilities of suicide on Monday were 9% and 10% higher,
      respectively, than those on Sunday. As age increased, the differences in suicide
      probability according to the day of the week were attenuated. The so-called Blue
      Monday effect is real, particularly for people in their teens and 20s. Suicide
      prevention strategies that aim to attenuate the burden and stress of Mondays
      should be planned.

PMID- 29349807
TI  - Possible role of plasmacytoid dendritic cells in pityriasis lichenoides.
AB  - BACKGROUND: Plasmacytoid dendritic cells (pDCs) and their product, type I
      interferons (IFNs), have been implicated in the pathogenesis of several skin
      disorders characterized by an interface dermatitis (ID) pattern, such as lichen
      planus (LP). A type I IFN signature has previously been documented in pityriasis
      lichenoides (PL). Although pDCs are known to be the main source and most potent
      producers of local type I IFNs, their role in PL has not been investigated. AIM:
      To investigate the role of pDCs in PL. METHODS: In total, 20 cases of PL and 20
      comparable cases of LP were immunohistochemically tested for pDC occurrence and
      type I IFN production using anti-blood-derived dendritic cell antigen-2 (BDCA2; a
      specific pDC marker) and anti-myxovirus protein A (anti-MxA) antibodies (indirect
      marker of pDC activity), respectively. MxA is a well-established surrogate marker
      for local type 1 IFN production. A semiquantitative scoring system was used.
      RESULTS: pDCs were present in all 40 cases with no statistically significant
      difference between the two groups. MxA expression was intense and diffuse in the
      majority of PL and LP cases. CONCLUSIONS: pDCs constitute a central component of
      the inflammatory infiltrate in PL, suggesting that PL shares with the other
      entities that exhibit an ID a common pDC-driven process through type I IFN
      production, which ultimately leads to the cytotoxic attack.

PMID- 29349808
TI  - Promises and pitfalls in the development of biomarkers that can promote early
      intervention in children at risk.
AB  - The cost to individuals and to society of psychopathology that emerges in
      childhood is substantial. Children whose problems are undiagnosed or inadequately
      treated struggle in school, experience rejection by peers, and become a source of
      stress for caregivers and teachers. As adults, their mental health problems tend
      to recur and their cognitive difficulties persist. Clinicians hold a well-founded
      belief that early identification of children who are at risk for psychopathology
      is the key to prevention.

PMID- 29349809
TI  - Alexithymia as a potential source of symptom over-reporting: An exploratory study
      in forensic patients and non-forensic participants.
AB  - The traditional interpretation of symptom over-reporting is that it indicates
      malingering. We explored a different perspective, namely that over-reporting of
      eccentric symptoms is related to deficits in articulating internal experiences
      (i.e., alexithymia). Given that alexithymia has been linked to sleep problems and
      that fatigue may fuel inattentive responding to symptom lists, we administered
      measures of alexithymia (TAS-20) and symptom over-reporting (SIMS), but also
      sleep quality (SLEEP-50) to forensic psychiatric outpatients (n = 40) and non
      forensic participants (n = 40). Forensic patients scored significantly higher on
      all three indices than non-forensic participants. In the total sample as well as
      in subsamples, over-reporting correlated positively and significantly with
      alexithymia, with rs being in the 0.50-0.65 range. Sleep problems were also
      related to over-reporting, but in the full sample and in the forensic subsample,
      alexithymia predicted variance in over-reporting over and above sleep problems.
      Although our study is cross-sectional in nature, its results indicate that
      alexithymia as a potential source of over-reporting merits systematic research.

PMID- 29349810
TI  - Medicago truncatula copper transporter 1 (MtCOPT1) delivers copper for symbiotic
      nitrogen fixation.
AB  - Copper is an essential nutrient for symbiotic nitrogen fixation. This element is
      delivered by the host plant to the nodule, where membrane copper (Cu) transporter
      would introduce it into the cell to synthesize cupro-proteins. COPT family
      members in the model legume Medicago truncatula were identified and their
      expression determined. Yeast complementation assays, confocal microscopy and
      phenotypical characterization of a Tnt1 insertional mutant line were carried out
      in the nodule-specific M. truncatula COPT family member. Medicago truncatula
      genome encodes eight COPT transporters. MtCOPT1 (Medtr4g019870) is the only
      nodule-specific COPT gene. It is located in the plasma membrane of the
      differentiation, interzone and early fixation zones. Loss of MtCOPT1 function
      results in a Cu-mitigated reduction of biomass production when the plant obtains
      its nitrogen exclusively from symbiotic nitrogen fixation. Mutation of MtCOPT1
      results in diminished nitrogenase activity in nodules, likely an indirect effect
      from the loss of a Cu-dependent function, such as cytochrome oxidase activity in
      copt1-1 bacteroids. These data are consistent with a model in which MtCOPT1
      transports Cu from the apoplast into nodule cells to provide Cu for essential
      metabolic processes associated with symbiotic nitrogen fixation.

PMID- 29349811
TI  - Genetic analysis of interleukin 18 gene polymorphisms in alopecia areata.
AB  - BACKGROUND: Alopecia areata (AA), which appears as nonscarring hair shedding on
      any hair-bearing area, is a common organ-specific autoimmune condition. Cytokines
      have important roles in the development of AA. Interleukin (IL) 18 is a
      significant proinflammatory cytokine that was found higher in the patients with
      AA. We aimed to investigate whether the IL-18 (rs187238 and rs1946518) single
      nucleotide polymorphisms (SNPs) may be associated with AA and/or clinical outcome
      of patients with AA in Turkish population. METHODS: Genotyping of rs187238 and
      rs1946518 SNPs were detected using sequence-specific primer-polymerase chain
      reaction (SSP-PCR) method in 200 patients with AA and 200 control subjects.
      RESULTS: The genotype distribution of rs1946518 (-607C>A) SNP was found to be
      statistically significantly different among patients with AA and controls (P =
      .0008). Distribution of CC+CA genotypes and frequency of -607/allele C of
      rs1946518 SNP were higher in patients with AA (P = .001, P = .001, respectively).
      The genotype distribution of rs187238 (-137G>C) SNP was found to be statistically
      significantly different among patients with AA and control subjects (P = .0014).
      Distribution of GG genotype and frequency of -137/allele G of rs187238 SNP were
      higher in patients with AA (P = .0003, P = .001, respectively). CONCLUSION: The
      rs1946518 (-607C>A) and rs187238 (-137G>C) polymorphisms were found associated
      with alopecia areata disease. The study suggests that IL-18 rs187238 and
      rs1946518 SNPs may be the cause of the AA susceptibility.

PMID- 29349812
TI  - Drug promotion practices: A review.
AB  - Over the years, the pharmaceutical industry has been at the forefront of research
      and innovation in drug discovery and development. The process of drug discovery
      extending from preclinical studies to multicentric clinical trials and
      postmarketing phase is a costly affair running into billions of dollars. On the
      flip side, not all investigational molecules clear the trial phases and get
      approved, which puts pressure on the manufacturers to maximize the profit from
      approved drugs. It is in this key area that the practice of drug promotion plays
      its role. The World Health Organization defines drug promotion as "all
      informational and persuasive activities by manufacturers and distributors, the
      effect of which is to influence the prescription, supply, purchase or use of
      medicinal drugs". With its humble intent of creating awareness among healthcare
      professionals and updating their knowledge on recent advances in treatment
      options, drug promotion has been an important tool, but gradually it has evolved
      to embrace aggressive marketing strategies and sometimes unethical business and
      scientific practices where the need for profit-making eclipses commitment to
      patient care and scientific exploration. In this review, we discuss the evolution
      of drug promotion practices, the various types, its merits and demerits, the
      influence of drug promotion on physician prescribing behaviour, the role of
      regulatory bodies, unethical promotional practices and finally summarize with
      future directions.

PMID- 29349813
TI  - HLA-B27 testing: A journey from flow cytometry to molecular subtyping.
AB  - BACKGROUND: Determination of HLA-B27 status plays an important role as adjuvant
      in suspected cases for diagnosis of Ankylosing Spondilytis (AS). Objectives of
      this study were to evaluate (i) flow cytometry method in comparison with DNA
      microarray for HLA-B27 typing and (ii) EUROArray HLA-B27 Direct assay for HLA-B27
      allele detection along with discrimination of AS/non-AS subtypes in Indian
      population. METHODS: A total of 7543 patients with a presumptive clinical
      diagnosis of AS were referred for screening of HLA-B27. All samples were
      initially tested by flow cytometry, and based on its findings, 1560 samples were
      analyzed for the presence of HLA-B27 allele by microarray technology. A subset of
      samples (n = 200) were further tested by DNA sequencing for identification of HLA
      B27 subtypes. RESULTS: Screening of HLA-B27 by flow cytometry reported 1551
      positive (20.56%) and 5556 negative (73.65%) cases. Remaining 436 (5.78%) samples
      were identified within equivocal zone. Of cases (n = 1560) analyzed by microarray
      method, 1333 (85.44%) and 227 (14.55%) were detected microarray positive and
      negative, respectively. DNA sequencing identified HLA-B*27:07 as the predominant
      subtype among cases showing ex2 positivity by microarray method. Of 200 cases, 20
      cases (14 of HLA-B*07 and 6 of HLA-B*37) of HLA-B27 cross-reactive subtypes were
      also identified. CONCLUSION: We recommend DNA typing as a complementary tool
      along with flow cytometry to accomplish successful HLA-B27 phenotype
      determination. This is the first study among Indian population to evaluate
      efficacy of EUROArray to detect B27 allele and its potential to indicate the
      presence of nondisease-associated alleles in Indian population.

PMID- 29349814
TI  - VO2 /TiN Plasmonic Thermochromic Smart Coatings for Room-Temperature
      Applications.
AB  - Vanadium dioxide/titanium nitride (VO2 /TiN) smart coatings are prepared by
      hybridizing thermochromic VO2 with plasmonic TiN nanoparticles. The VO2 /TiN
      coatings can control infrared (IR) radiation dynamically in accordance with the
      ambient temperature and illumination intensity. It blocks IR light under strong
      illumination at 28  degrees C but is IR transparent under weak irradiation
      conditions or at a low temperature of 20  degrees C. The VO2 /TiN coatings
      exhibit a good integral visible transmittance of up to 51% and excellent IR
      switching efficiency of 48% at 2000 nm. These unique advantages make VO2 /TiN
      promising as smart energy-saving windows.

PMID- 29349815
TI  - Erratum: An assessment of differences in costs and health benefits of serology
      and NAT screening of donations for blood transfusion in different Western
      countries.

PMID- 29349817
TI  - Anatomical study of the so-called "retromolar gland": Distinguishing normal
      anatomy from oral cavity pathology.
AB  - The minor salivary glands in the retromolar trigone have rarely been studied. The
      aim of this study was to better define the anatomy of the minor salivary glands
      in the retromolar trigone and establish the relationships between these and
      adjacent structures. The gland in the retromolar trigone was exposed and its
      relationships to surrounding structures were observed on 20 cadaveric sides. The
      boundaries of the gland included the superior pharyngeal constrictor muscle, the
      tendon of the buccinator muscle, and loose connective tissue. The gland was not
      continuous with the pterygomandibular or parapharyngeal spaces, but loose
      connective tissue was present between glands in the retromolar trigone and the
      medial pterygoid muscle. To our knowledge, this is the first study to describe
      the detailed anatomy of the minor salivary gland in the retromolar trigone. We
      suggest that the minor salivary gland in the retromolar trigone should be named
      the "retromolar gland." Clin. Anat. 31:462-465, 2018. (c) 2018 Wiley Periodicals,
      Inc.

PMID- 29349818
TI  - Nanocrystalline Precursors for the Co-Assembly of Crack-Free Metal Oxide Inverse
      Opals.
AB  - Inorganic microstructured materials are ubiquitous in nature. However, their
      formation in artificial self-assembly systems is challenging as it involves a
      complex interplay of competing forces during and after assembly. For example,
      colloidal assembly requires fine-tuning of factors such as the size and surface
      charge of the particles and electrolyte strength of the solvent to enable
      successful self-assembly and minimize crack formation. Co-assembly of templating
      colloidal particles together with a sol-gel matrix precursor material helps to
      release stresses that accumulate during drying and solidification, as previously
      shown for the formation of high-quality inverse opal (IO) films out of amorphous
      silica. Expanding this methodology to crystalline materials would result in
      microscale architectures with enhanced photonic, electronic, and catalytic
      properties. This work describes tailoring the crystallinity of metal oxide
      precursors that enable the formation of highly ordered, large-area (mm2 ) crack
      free titania, zirconia, and alumina IO films. The same bioinspired approach can
      be applied to other crystalline materials as well as structures beyond IOs.

PMID- 29349819
TI  - Incidence and predictors of sudden cardiac death after heart transplantation: A
      systematic review and meta-analysis.
AB  - PURPOSE: Sudden cardiac death (SCD) is an important post-transplant problem being
      responsible for ~10% of deaths. We conducted a systematic review and meta
      analysis to evaluate incidence and predictors of post-heart transplant SCD and
      the use of implantable cardiac defibrillator (ICD). METHODS: Citations were
      identified in electronic databases and references of included studies.
      Observational studies on adults reporting on incidence and predictors of post
      transplant SCD and ICD use were selected. We meta-analyzed SCD in person-years
      using random effects models. We qualitatively summarized predictors. RESULTS:
      This study includes 55 studies encompassing 47 901 recipients. The pooled
      incidence rate of SCD was 1.30 per 100 person-years (95% CI: 1.08-1.52). Cardiac
      allograft vasculopathy (CAV) was associated with higher SCD risk (2.40 per 100
      patient-years, 95% CI: 1.46-3.34). Independent predictors of SCD identified by
      two moderate-quality studies were older donor age, younger recipient age, non
      Caucasian race, reduced left ventricular ejection fraction, rejection, infection,
      and cancer. Authors rarely reported on ICD use. CONCLUSION: This meta-analysis
      found that post-transplant SCD risk in heart transplant recipients is higher than
      that in the general population. CAV was associated with increased SCD risk.
      Observational studies reporting on absolute risk of SCD are needed to better
      identify populations at a clinically significant increased risk.

PMID- 29349820
TI  - An experimental test of alternative population augmentation scenarios.
AB  - Human land use is fragmenting habitats worldwide and inhibiting dispersal among
      previously connected populations of organisms, often leading to inbreeding
      depression and reduced evolutionary potential in the face of rapid environmental
      change. To combat this augmentation of isolated populations with immigrants is
      sometimes used to facilitate demographic and genetic rescue. Augmentation with
      immigrants that are genetically and adaptively similar to the target population
      effectively increases population fitness, but if immigrants are very genetically
      or adaptively divergent, augmentation can lead to outbreeding depression. Despite
      well-cited guidelines for the best practice selection of immigrant sources, often
      only highly divergent populations remain, and experimental tests of these riskier
      augmentation scenarios are essentially nonexistent. We conducted a mesocosm
      experiment with Trinidadian guppies (Poecilia reticulata) to test the
      multigenerational demographic and genetic effects of augmenting 2 target
      populations with 3 types of divergent immigrants. We found no evidence of
      demographic rescue, but we did observe genetic rescue in one population.
      Divergent immigrant treatments tended to maintain greater genetic diversity,
      abundance, and hybrid fitness than controls that received immigrants from the
      source used to seed the mesocosms. In the second population, divergent immigrants
      had a slightly negative effect in one treatment, and the benefits of augmentation
      were less apparent overall, likely because this population started with higher
      genetic diversity and a lower reproductive rate that limited genetic admixture.
      Our results add to a growing consensus that gene flow can increase population
      fitness even when immigrants are more highly divergent and may help reduce
      uncertainty about the use of augmentation in conservation.

PMID- 29349821
TI  - Biodegradable Electronic Systems in 3D, Heterogeneously Integrated Formats.
AB  - Biodegradable electronic systems represent an emerging class of technology with
      unique application possibilities, from temporary biomedical implants to "green"
      consumer gadgets. This paper introduces materials and processing methods for 3D,
      heterogeneously integrated devices of this type, with various functional examples
      in sophisticated forms of silicon-based electronics. Specifically, techniques for
      performing multilayer assembly by transfer printing and for fabricating layer-to
      layer vias and interconnects by lithographic procedures serve as routes to
      biodegradable, 3D integrated circuits composed of functional building blocks
      formed using specialized approaches or sourced from commercial semiconductor
      foundries. Demonstration examples range from logic gates and analog circuits that
      undergo functional transformation by transience to systems that integrate
      multilayer resistive sensors for in situ, continuous electrical monitoring of the
      processes of transience. The results significantly expand the scope of
      engineering options for biodegradable electronics and other types of transient
      microsystem technologies.

PMID- 29349822
TI  - Subcritical water extraction of amino acids from Mars analog soils.
AB  - For decades, the Martian regolith has stymied robotic mission efforts to catalog
      the organic molecules present. Perchlorate salts, found widely throughout Mars,
      are the main culprit as they breakdown and react with organics liberated from the
      regolith during pyrolysis, the primary extraction technique attempted to date on
      Mars. This work further develops subcritical water extraction (SCWE) as a
      technique for extraction of amino acids on future missions. The effect of SCWE
      temperature (185, 200, and 215 degrees C) and duration of extraction (10-120 min)
      on the total amount and distribution of amino acids recovered was explored for
      three Mars analog soils (JSC Mars-1A simulant, an Atacama desert soil, and an
      Antarctic Dry Valleys soil) and bovine serum albumin (as a control solution of
      known amino acid content). Total amounts of amino acids extracted increased with
      both time and temperature; however, the distribution shifted notably due to the
      destruction of the amino acids with charged or polar side chains at the higher
      temperatures. The pure bovine serum albumin solution and JSC Mars 1A also showed
      lower yields than the Atacama and Antarctic extractions suggesting that SCWE may
      be less effective at hydrolyzing large or aggregated proteins. Changing solvent
      from water to a dilute (10 mM) HCl solution allowed total extraction efficiencies
      comparable to the higher temperature/time combinations while using the lowest
      temperature/time (185 degrees C/20 min). The dilute HCl extractions also did not
      lead to the shift in amino acid distribution observed at the higher temperatures.
      Additionally, adding sodium perchlorate salt to the extraction did not interfere
      with recoveries. Native magnetite in the JSC Mars-1A may have been responsible
      for destruction of glycine, as evidenced by its uncharacteristic decrease as the
      temperature/time of extraction increased. This work shows that SCWE can extract
      high yields of native amino acids out of Mars analog soils with minimal
      disruption of the distribution of those amino acids, even in the presence of a
      perchlorate salt.

PMID- 29349823
TI  - Tibolone and risk of gynecological hormone sensitive cancer.
AB  - Risk of ovarian cancer with hormone therapy is associated with use of both
      unopposed estrogen therapy and combined estrogen-progestin therapy, whereas for
      endometrial cancer addition of continuous progestin decreases the estrogen
      induced increased risk. Less is known about risk with use of tibolone; a
      synthetic steroid with estrogenic, progestagenic and androgenic properties. We
      assessed these associations in a prospective cohort study, including all Danish
      women 50-79 years of age and followed 1995-2009. National Danish Registers
      captured individually updated exposure information, cancer cases including
      histology and confounding factors. Poisson regression analyses provided multiple
      adjusted incidence rate ratios (IRRs). More than 900,000 women were followed for
      9.8 years on average; 4,513 were diagnosed with ovarian cancer and 6,202 with
      endometrial cancer. Compared to women never on postmenopausal hormone therapy,
      current users of tibolone had an increased IRR for ovarian cancer (1.42(95%
      confidence interval [CI], 1.01-2.00) and serous ovarian tumors (2.21(95%CI 1.48
      3.32)). The risk increased with duration of use, particularly for serous ovarian
      tumors. Compared to never users, the IRR of endometrial cancer was 3.56(95%CI
      2.94-4.32) among current users of tibolone and 3.80(95%CI 3.08-4.69) of Type I
      endometrial cancer. The steepest risk increase with duration of use was for Type
      I tumors. In conclusion, tibolone is associated with increased risk for ovarian
      and endometrial cancer overall; and particular the risk of serous ovarian tumors
      and Type I endometrial cancer. Because the associations are stronger with
      increasing durations of use - and for hormone sensitive tumors - the results seem
      indicative of causality.

PMID- 29349824
TI  - Reduced left ventricular filling following blood volume extraction does not
      result in compensatory augmentation of cardiac mechanics.
AB  - NEW FINDINGS: What is the central question of this study? A reduction in left
      ventricular (LV) filling, and concomitant increase in heart rate, augments LV
      mechanics to maintain stroke volume (SV); however, the impact of reduced LV
      filling in isolation on SV and LV mechanics is currently unknown. What is the
      main finding and its importance? An isolated decrease in LV filling did not
      provoke a compensatory increase in mechanics to maintain SV; in contrast, LV
      mechanics and SV were reduced. These data indicate that when LV filling is
      reduced without changes in heart rate, LV mechanics do not compensate to maintain
      SV. ABSTRACT: An acute non-invasive reduction in preload has been shown to
      augment cardiac mechanics to maintain stroke volume and cardiac output. Such
      interventions induce concomitant changes in heart rate, whereas blood volume
      extraction reduces preload without changes in heart rate. Therefore, the purpose
      of this study was to determine whether a preload reduction in isolation resulted
      in augmented stroke volume achieved via enhanced cardiac mechanics. Nine healthy
      volunteers (four female, age 29 +/- 11 years) underwent echocardiography for the
      assessment of left ventricular (LV) volumes and mechanics in a supine position at
      baseline and end extraction after the controlled removal of 25% of total blood
      volume (1062 +/- 342 ml). Arterial blood pressure was monitored continuously by a
      pressure transducer attached to an indwelling radial artery catheter. Heart rate
      and total peripheral resistance were unchanged from baseline to end extraction,
      but systolic blood pressure was reduced (from 148 to 127 mmHg). From baseline to
      end extraction there were significant reductions in left ventricular end
      diastolic volume (from 89 to 71 ml) and stroke volume (from 56 to 37 ml);
      however, there was no change in LV twist, basal or apical rotation. In contrast,
      LV longitudinal strain (from -20 to -17%) and basal circumferential strain (from 
      22 to -19%) were significantly reduced from baseline to end extraction. In
      conclusion, a reduction in preload during blood volume extraction does not result
      in compensatory changes in stroke volume or cardiac mechanics. Our data suggest
      that LV strain is dependent on LV filling and consequent geometry, whereas LV
      twist could be mediated by heart rate.

PMID- 29349825
TI  - Synthesis of Single and Double Dibenzohelicenes by Rhodium-Catalyzed
      Intramolecular [2+2+2] and [2+1+2+1] Cycloaddition.
AB  - Dibenzo[7]helicenes were synthesized with up to 99 % ee by rhodium(I)/binap
      catalyzed enantioselective intramolecular [2+2+2] cycloaddition of 2
      phenylnaphthalene-linked triynes. Additionally, [2+1+2+1] cycloaddition products,
      that is, twisted anthracenes, were also synthesized by using difluorphos as
      ligand. Although these compounds are not configurationally stable at elevated
      temperature, their Scholl reactions afforded configurationally stable double
      dibenzo[6]helicenes. The thus-obtained dibenzo[7]helicene exhibited good
      circularly polarized luminescence property and the double dibenzo[6]helicene
      showed high fluorescence quantum yield.

PMID- 29349826
TI  - Low performance on mathematical tasks in preschoolers: the importance of domain
      general and domain-specific abilities.
AB  - BACKGROUND: Different domain-specific and domain-general cognitive precursors
      play a key role in the development of mathematical abilities. The contribution of
      these domains to mathematical ability changes during development. Primary school
      aged children who show mathematical difficulties form a heterogeneous group, but
      it is not clear whether this also holds for preschool low achievers (LAs) and how
      domain-specific and domain-general abilities contribute to mathematical
      difficulties at a young age. The aim of this study was to explore the cognitive
      characteristics of a sample of preschool LAs and identify sub-types of LAs.
      METHODS: 81 children were identified as LAs from 283 preschoolers aged 3 to 5
      years old and were assessed on a number of domain-general and domain-specific
      tasks. RESULTS: Cluster analysis revealed four subgroups of LAs in mathematics:
      (1) a weak processing sub-type; (2) a general mathematical LAs sub-type; (3) a
      mixed abilities sub-type; and (4) a visuo-spatial deficit sub-type. Whilst two of
      the groups showed specific domain-general difficulties, none showed only domain
      specific difficulties. CONCLUSIONS: Current findings suggest that preschool LAs
      constitute a heterogeneous group and stress the importance of domain-general
      factors for the development of mathematical abilities during the preschool years.

PMID- 29349827
TI  - Underwater Mechanically Robust Oil-Repellent Materials: Combining Conflicting
      Properties Using a Heterostructure.
AB  - The development of underwater mechanically robust oil-repellent materials is
      important due to the high demand for these materials with the increase in
      underwater activities. Based on the previous study, a new strategy is
      demonstrated to prepare underwater mechanically robust oil-repellent materials by
      combining conflicting properties using a heterostructure, which has a layered
      hydrophobic interior structure with a columnar hierarchical micro/nanostructure
      on the surface and a hydrophilic outer structure. The surface hydrophilic layer
      imparts underwater superoleophobicity and low oil adhesion to the material, which
      has oil contact angle of larger than 150 degrees  and adhesion of lower than 2.8
      uN. The stability of the mechanical properties stemming from the interior
      hydrophobic-layered structure enables the material to withstand high weight loads
      underwater. The tensile stress and the hardness of such a heterostructure film
      after 1 month immersion in seawater and pH solution are in the range from 83.92
      +/- 8.22 to 86.73 +/- 7.8 MPa and from 83.88 +/- 6.8 to 86.82 +/- 5.64 MPa,
      respectively, which are superior to any underwater oil-repellent material
      currently reported.

PMID- 29349828
TI  - Further Evidence That Sleep Deprivation Effects and the Vigilance Decrement Are
      Functionally Equivalent: Comment on Altmann (2018).
AB  - Veksler and Gunzelmann (2018) argue that the vigilance decrement and the
      deleterious effects of sleep loss reflect functionally equivalent degradations in
      cognitive processing and performance. Our account is implemented in a cognitive
      architecture, where these factors produce breakdowns in goal-directed cognitive
      processing that we refer to as microlapses. Altmann (2018) raises a number of
      challenges to microlapses as a unified account of these deficits. Under scrutiny,
      however, the challenges do little to discredit the theory or conclusions in the
      original paper. In our response, we address the most serious challenges. In so
      doing, we provide additional support for the theory and mechanisms, and we
      highlight opportunities for extending their explanatory breadth.

PMID- 29349829
TI  - Physicians' perspective on the clinical meaningfulness of inflammatory bowel
      disease trial results: an International Organization for the Study of
      Inflammatory Bowel Disease (IOIBD) survey.
AB  - BACKGROUND: Several novel compounds are being developed for inflammatory bowel
      diseases (IBD). In addition, biosimilar drugs are being approved. An increasing
      number of head-to-head, superiority and non-inferiority trials in patients with
      IBD are expected in the future. The clinical relevance of the magnitude of the
      effect size is often debated. AIM: To better understand physicians' perspectives
      on the clinical meaningfulness of IBD trial results. METHODS: We conducted an
      online survey among all IOIBD (International Organization for the Study of
      Inflammatory Bowel Diseases) members, asking their opinion on the clinical
      relevance of the results of IBD trials. RESULTS: Forty-six IOIBD members
      responded to the survey (52.3%). In biologic-naive ulcerative colitis (UC) and
      Crohn's disease (CD) patients, most of the participants considered a 15%
      difference with placebo for clinical remission and endoscopic remission to be
      clinically relevant. In head-to-head trials, most of participants considerer a
      10% difference between groups for clinical remission and endoscopic remission to
      be clinically relevant. Half of respondents considered 10% to be an adequate
      margin in non-inferiority trials. In bioequivalence studies, most of the
      participants considered adequate a +/- 5% difference between a biosimilar and the
      originator for pharmacokinetic parameters, efficacy, safety and immunogenicity.
      Regarding safety, the difference between two drugs considered clinically relevant
      varied from 1% to 5%, depending on the type of adverse event. CONCLUSIONS: This
      is the first survey exploring how physicians perceive IBD trial results,
      providing an estimation of the magnitude of the difference between treatment arms
      that may directly influence clinical practice.

PMID- 29349830
TI  - Synthesis and Structure of a Longitudinally Twisted Hexacene.
AB  - The addition of phenyllithium to a polycyclic quinone, 9,11,12,21,22,24
      hexaphenyltetrabenzo[a,c,n,p]hexacene-10,23-dione (10), followed by SnCl2 
      mediated reduction of the diol intermediate, yielded 9,10,11,12,21,22,23,24
      octaphenyltetrabenzo-[a,c,n,p]hexacene (4). Crystallographic analysis of hexacene
      4 showed it to possess a longitudinal twist of 184 degrees , which was in good
      agreement with AM1 calculations. In addition to being the most twisted acene
      synthesized to this point, compound 4 contains within its substructure the most
      twisted naphthalene, anthracene, tetracene, and pentacene moieties described.

PMID- 29349832
TI  - Effects of yoga interventions practised in heated and thermoneutral conditions on
      endothelium-dependent vasodilatation: The Bikram yoga heart study.
AB  - NEW FINDINGS: What is the central question of this study? Does the heated
      practice environment enhance the effects of Bikram yoga on endothelium-dependent
      vasodilatation in healthy, middle-aged adults? What is the main finding and its
      importance? The primary finding from this investigation is that the hatha yoga
      postures in the Bikram yoga series produce similar enhancements in endothelium
      dependent vasodilatation in healthy, middle-aged adults regardless of
      environmental temperature. These findings highlight the efficacy of yoga postures
      in producing improvements in vascular health and downplay the necessity of the
      heated practice environment in inducing vascular adaptations. ABSTRACT: We have
      previously documented improvements in endothelium-dependent vasodilatation with a
      Bikram (hot) yoga intervention in middle-aged adults. At present, the effect of
      environmental temperature in hot yoga on endothelial function is unknown. The
      purpose of this investigation was to determine the effects of Bikram yoga
      interventions performed in heated or thermoneutral conditions on endothelium
      dependent vasodilatation. Fifty-two sedentary but apparently healthy adults aged
      40-60 years were randomly assigned to one of three groups: Bikram yoga practised
      at 40.5 degrees C (n = 19), Bikram yoga practised at 23 degrees C (n = 14) or
      sedentary time control (n = 19). The yoga interventions consisted of 90 min
      Bikram yoga classes three times a week for 12 weeks. Endothelium-dependent
      vasodilatation was measured non-invasively using brachial artery flow-mediated
      dilatation (FMD). Body fat percentage determined via dual-energy X-ray
      absorptiometry was significantly lower in the hot yoga group after the
      intervention than in the thermoneutral yoga and control conditions. Brachial
      artery FMD increased (P < 0.05) in the thermoneutral yoga group and tended to
      increase in the hot yoga group (P = 0.056). No changes occurred in the control
      group. There were no significant differences in FMD change scores between groups.
      We conclude that Bikram yoga practised in thermoneutral conditions improved
      endothelium-dependent vasodilatation in healthy, middle-aged adults. These new
      findings highlight the effectiveness of hatha yoga postures alone, in the absence
      of a heated practice environment, in improving vascular health and are of
      clinical significance given the increased propensity for heat intolerance in
      ageing adults.

PMID- 29349833
TI  - A systematic assessment of key design and performance characteristics of drug
      exposure registries requested by the U.S. Food and Drug Administration.
AB  - PURPOSE: The purpose of the study is to evaluate contributions to postmarket
      safety assessments and identify potential factors for enhancing implementation
      and utilization of registries in regulatory decision-making. METHODS: Registry
      documents (e.g., protocols, reports) submitted to the FDA were identified up to
      January 2016 through an extensive, systematic review of internal records and
      resources. We characterized nonpregnancy drug exposure registries based on
      prespecified design elements, performance, and regulatory impact. RESULTS: A
      total of 65 registries were identified: 56 registries were open and 9 closed.
      Among open registries, 20% were pending, 14% delayed, and 16% ongoing less than
      <=3 years. Most registries (82%) examined safety issues that originally arose
      from clinical trials; most frequent safety issues investigated included
      infections, gastrointestinal dysfunction, and liver toxicity. Although 74% of
      registries ascertained baseline health conditions and monitored concomitant
      medication use, fewer (45%) considered drug exposure duration or dosage. Thirty
      seven percent of non pending registries had enrollment below sample size
      expectation. Seventeen registries published findings in journals/conference
      proceedings, 13 from open registries. Three closed registries generated results
      that contributed to product label changes. High-performance registries scored
      higher in design metrics related to sample size considerations (76% versus 62%)
      and adequate analysis plan (53% versus 35%), and interim report submission (76%
      versus 65%). There was a significant difference in proportion of registries with
      clear primary objectives between high versus not high performing registries (100%
      versus 78%). CONCLUSIONS: This study suggests clear objectives, patient
      accrual/retention efforts, adequate analysis plans, and interim reports
      contribute to the performance of drug exposure registries.

PMID- 29349831
TI  - Aortic dysfunction in metabolic syndrome mediated by perivascular adipose tissue
      TNFalpha- and NOX2-dependent pathway.
AB  - NEW FINDINGS: What is the central question of this study? Tumour necrosis factor
      alpha (TNFalpha) has been shown to impair vascular function, but the impact of
      thoracic aorta perivascular adipose tissue (tPVAT)-derived TNFalpha on tPVAT and
      aortic function in metabolic syndrome is unknown. What is the main finding and
      its importance? Release of TNFalpha by tPVAT causes production of reactive oxygen
      species in tPVAT through activation of an NADPH-oxidase 2 (NOX2)-dependent
      pathway, activates production of aortic reactive oxygen species and mediates
      aortic stiffness, potentially through matrix metalloproteinase 9 activity.
      Neutralization of TNFalpha and/or inhibition of NOX2 blocks the tPVAT-induced
      impairment of aortic function. These data partly implicate tPVAT NOX2 and
      TNFalpha in mediating the vascular pathology of metabolic syndrome. ABSTRACT:
      Perivascular adipose tissue (PVAT) is recognized for its vasoactive effects, but
      it is unclear how metabolic syndrome impacts thoracic aorta (t)PVAT and the
      subsequent effect on functional and structural aortic stiffness. Thoracic aorta
      and tPVAT were removed from 16- to 17-week-old lean (LZR, n = 16) and obese
      Zucker rats (OZR, n = 16). The OZR presented with aortic endothelial dysfunction,
      assessed by wire myography, and increased aortic stiffness, assessed by elastic
      modulus. The OZR tPVAT exudate further exacerbated the endothelial dysfunction,
      reducing nitric oxide and endothelium-dependent relaxation (P < 0.05).
      Additionally, OZR tPVAT exudate had increased MMP9 activity (P < 0.05) and
      further increased the elastic modulus of the aorta after 72 h of co-culture (P <
      0.05). We found that the observed aortic dysfunction caused by OZR tPVAT was
      mediated through increased production and release of tumour necrosis factor-alpha
      (TNFalpha; P < 0.01), which was dependent on tPVAT NADPH-oxidase 2 (NOX2)
      activity. The OZR tPVAT release of reactive oxygen species and subsequent aortic
      dysfunction were inhibited by TNFalpha neutralization and/or inhibition of NOX2.
      Additionally, we found that OZR tPVAT had reduced activity of the active sites of
      the 20S proteasome (P < 0.05) and reduced superoxide dismutase activity (P <
      0.01). In conclusion, metabolic syndrome causes tPVAT dysfunction through an
      interplay between TNFalpha and NOX2 that leads to tPVAT-mediated aortic stiffness
      by activation of aortic reactive oxygen species and increased MMP9 activity.

PMID- 29349834
TI  - Drug adherence in treatment resistant and in controlled hypertension-Results from
      the Swedish Primary Care Cardiovascular Database (SPCCD).
AB  - PURPOSE: To assess drug adherence in patients treated with >=3 antihypertensive
      drug classes, with both controlled and uncontrolled blood pressure and describe
      associated factors for nonadherence. METHODS: Patients with hypertension, without
      cardiovascular comorbidity, aged >30 years treated with >=3 antihypertensive drug
      classes were followed for 2 years. Both patients with treatment resistant
      hypertension (TRH) and patients with controlled hypertension were included.
      Clinical data were derived from a primary care database. Pharmacy refill data
      from the Swedish Prescribed drug registry was used to calculate proportion of
      days covered (PDC). Patients with a PDC level >= 80% were included. RESULTS: We
      found 5846 patients treated >=3 antihypertensive drug classes, 3508 with TRH
      (blood pressure >= 140/90), and 2338 with controlled blood pressure (<140/90 mm
      Hg). TRH patients were older (69.1 vs 65.8 years, P < .0001) but had less
      diabetes (28.5 vs 31.7%, P < .009) compared with patients with controlled blood
      pressure. The proportion of patients with PDC >= 80% declined with 11% during the
      first year in both groups. Having diabetes was associated with staying adherent
      at 1 year (RR 0.82; 95% CI, 0.68-0.98) whilst being born outside Europe was
      associated with nonadherence at one and (RR 2.05; 95% CI, 1.49-2.82).
      CONCLUSIONS: Patients with multiple antihypertensive drug therapy had similar
      decline in adherence over time regardless of initial blood pressure control.
      Diabetes was associated with better adherence, which may imply that the
      structured caregiving of these patients enhances antihypertensive drug treatment.

PMID- 29349836
TI  - Evaluation of a West Australian residential mental health respite service.
AB  - Family members continue to be the predominant providers of support, care and
      accommodation for loved ones with mental health issues, and empirical studies
      suggest that accessing mental health respite can be helpful for both carers and
      consumers. However, the availability of, and access to, this respite in Australia
      is far from optimal. Major issues have also been identified such as low
      utilisation, the inappropriate and inflexible nature of services and the
      inability of services to respond to situations where multiple needs exist. This
      article presents findings from a small evaluation of a pilot residential respite
      service. Semi-structured interviews were conducted with eight family
      members/carers and four consumers using the service, and five service providers.
      In addition, anonymised sociodemographic information about all users of the
      service in the first 9 months of its operation were analysed. Reflecting the
      current limitations around respite options, the majority of family members/carers
      and consumers were appreciative of, and satisfied with, the service. The research
      highlighted issues such as availability and suitability of respite, particularly
      when consumers had multiple and unmet needs. Mental health residential respite is
      often a stopgap in crisis situations and intersects with the difficulty of
      planning respite and shortages in affordable supported accommodation.
      Furthermore, the ramifications of individualised funding for people with
      "psychosocial disability" in the new Australian National Disability Insurance
      Scheme (NDIS) remain unclear. While family members and carers may benefit
      indirectly from NDIS funding, it is especially important at this time that the
      need for more suitable, recovery-oriented respite services is highlighted.

PMID- 29349835
TI  - Optimization of Aqueous Extraction from Kalanchoe pinnata Leaves to Obtain the
      Highest Content of an Anti-inflammatory Flavonoid using a Response Surface Model.
AB  - INTRODUCTION: The medicinal plant Kalanchoe pinnata is a phenolic-rich species
      used worldwide. The reports on its pharmacological uses have increased by 70% in
      the last 10 years. The leaves of this plant are the main source of an unusual
      quercetin-diglycosyl flavonoid (QAR, quercetin arabinopyranosyl
      rhamnopyranoside), which can be easily extracted using water. QAR possess a
      strong in vivo anti-inflammatory activity. OBJECTIVE: To optimize the aqueous
      extraction of QAR from K. pinnata leaves using a three-level full factorial
      design. MATERIAL AND METHODS: After a previous screening design, time (x1 ) and
      temperature (x2 ) were chosen as the two independent variables for optimization.
      Freeze-dried leaves were extracted with water (20% w/v), at 30 degrees C, 40
      degrees C or 50 degrees C for 5, 18 or 30 min. QAR content (determined by HPLC
      DAD) and yield of extracts were analyzed. The optimized extracts were also
      evaluated for cytotoxicity. RESULTS: The optimal heating times for extract yield
      and QAR content were similar in two-dimensional (2D) surface responses (between
      12.8 and 30 min), but their optimal extraction temperatures were ranged between
      40 degrees C and 50 degrees C for QAR content and 30 degrees C and 38 degrees C
      for extract yield. A compromise region for both parameters was at the mean points
      that were 40 degrees C for the extraction temperature and 18 min for the total
      time. CONCLUSION: The optimized process is faster and spends less energy than the
      previous one (water; 30 min at 55 degrees C); therefore is greener and more
      attractive for industrial purposes. This is the first report of extraction
      optimization of this bioactive flavonoid. Copyright (c) 2018 John Wiley & Sons,
      Ltd.

PMID- 29349837
TI  - Human-specific phages infecting Enterococcus host strain MW47: are they reliable
      microbial source tracking markers?
AB  - AIM: The aim of this study was to determine the morphological diversity and
      environmental survival of human-specific phages infecting Enterococcus faecium
      host strain MW47, to support their use as microbial source tracking (MST)
      markers. METHODS AND RESULTS: Twenty phages capable of infecting strain MW47 were
      propagated and their morphologies were determined using transmission electron
      microscopy (TEM), which revealed that a heterogeneous group of phages was able to
      infect strain MW47. Three distinct morphologies from two different families
      (Myoviridae and Siphoviridae) were observed. In situ inactivation experiments
      were subsequently conducted to determine their environmental persistence.
      CONCLUSION: The findings revealed a statistically significant link between
      morphology and the rate of inactivation, with phages belonging to the Myoviridae
      family demonstrating more rapid inactivation in comparison to those belonging to
      the Siphoviridae family. SIGNIFICANCE AND IMPACT OF STUDY: The results suggest
      that while Enterococcus MW47 phages appear to be a potentially valuable MST
      tools, significant variations in the persistence of the different phages mean
      that the approach should be used with caution, as this may adversely affect the
      reliability of the approach, especially when comparing MW47 phage levels or the
      presence across different matrices (e.g. levels in sediments or shellfish). This
      highlights the importance of elucidating the ecological characteristics of newly
      proposed MST markers before they are used in full-scale MST investigations.

PMID- 29349838
TI  - Patent foramen ovale repair at the time of double lung transplantation: Necessary
      or not?
AB  - INTRODUCTION: Patient foramen ovale (PFO) is a common and often incidental
      intraoperative finding during lung transplantation (LTx). We sought to
      characterize the potential outcomes related to the decision making of whether the
      PFO was repaired or left unrepaired. METHODS: We retrospectively evaluated
      bilateral LTx recipients between 2005 and 2015 from our prospective database.
      Incidence of postoperative stoke, 90-day mortality, and overall survival was
      compared between the PFO-positive and PFO-negative groups, and secondly compared
      between repaired PFO (rPFO) and non-repaired PFO (nrPFO) groups. RESULTS: A total
      of 831 LTx recipients were analyzed: 185 PFO-positive (140 nrPFO, 45 rPFO) and
      646 PFO-negative. Study groups were similar with regard to age and comorbidity.
      The presence of PFO was not associated with a difference in postoperative stroke
      (P = .89) or 90-day mortality (P = .64). In patients with PFO, intraoperative
      repair resulted in a lower, but non-significant rate of stroke (0% vs 5%; P =
      .20) and no difference in mortality (P = .26). As expected, PFO and PFO repair
      were both associated with a higher incidence of cardiopulmonary bypass
      utilization, but no difference in pump-related complications. CONCLUSIONS: The
      protective effect of PFO repair remains unclear. However, it is not associated
      with an increased incidence of stroke or postoperative mortality following LTx.

PMID- 29349839
TI  - Inflammatory biomarkers and intellectual disability in patients with Down
      syndrome.
AB  - BACKGROUND: Intellectual disability (ID) is part of the Down syndrome (DS)
      phenotypic spectrum, but the exact molecular pathophysiology of ID in individuals
      with DS is not yet fully understood, with many research hypotheses still
      unproven. Basing on previous studies (which suggested a possible role of altered
      inflammatory response in DS-related ID), we assessed the serum levels of a number
      of inflammatory biomarkers [serum amyloid A (SAA), C-reactive protein (C-RP),
      high mobility group box-1 (HMGB1)] in a cohort of individuals with DS and healthy
      controls. METHODS: In total, 24 children diagnosed with DS and 12 healthy
      controls were enrolled, and all underwent detailed cognitive assessment. Also,
      serum SAA, C-RP and HMGB1 levels were measured in all recruited subjects and
      correlated to the severity of ID in the DS group. RESULTS: Serum SAA, C-RP and
      HMGB1 values were found to be significantly higher in the DS group compared with
      the healthy subjects (P = 0.001). In addition, serum HMGB1 levels positively
      correlated with C-RP and SAA in the DS group but not in the healthy controls.
      Only serum C-RP levels resulted inversely correlated (P < 0.01) with intelligence
      quotient (IQ); conversely, significant statistical correlations between serum SAA
      levels and IQ (as well as between HMGB1 and IQ) have been not found (P > 0.05).
      CONCLUSIONS: The levels of the determined markers were higher in DS individuals
      compared with (cognitively) healthy subjects, and CRP showed a negative
      correlation with IQ in children with DS.

PMID- 29349840
TI  - The Preference for Pointing With the Hand Is Not Universal.
AB  - Pointing is a cornerstone of human communication, but does it take the same form
      in all cultures? Manual pointing with the index finger appears to be used
      universally, and it is often assumed to be universally preferred over other
      forms. Non-manual pointing with the head and face has also been widely attested,
      but it is usually considered of marginal significance, both empirically and
      theoretically. Here, we challenge this assumed marginality. Using a novel
      communication task, we investigated pointing preferences in the Yupno of Papua
      New Guinea and in U.S. undergraduates. Speakers in both groups pointed at similar
      rates, but form preferences differed starkly: The Yupno participants used non
      manual pointing (nose- and head-pointing) numerically more often than manual
      pointing, whereas the U.S. participants stuck unwaveringly to index-finger
      pointing. The findings raise questions about why groups differ in their pointing
      preferences and, more broadly, about why humans communicate in the ways they do.

PMID- 29349841
TI  - Novel MOF-Derived Co@N-C Bifunctional Catalysts for Highly Efficient Zn-Air
      Batteries and Water Splitting.
AB  - Metal-organic frameworks (MOFs) and MOF-derived materials have recently attracted
      considerable interest as alternatives to noble-metal electrocatalysts. Herein,
      the rational design and synthesis of a new class of Co@N-C materials (C-MOF-C2-T)
      from a pair of enantiotopic chiral 3D MOFs by pyrolysis at temperature T is
      reported. The newly developed C-MOF-C2-900 with a unique 3D hierarchical rodlike
      structure, consisting of homogeneously distributed cobalt nanoparticles
      encapsulated by partially graphitized N-doped carbon rings along the rod length,
      exhibits higher electrocatalytic activities for oxygen reduction and oxygen
      evolution reactions (ORR and OER) than that of commercial Pt/C and RuO2 ,
      respectively. Primary Zn-air batteries based on C-MOF-900 for the oxygen
      reduction reaction (ORR) operated at a discharge potential of 1.30 V with a
      specific capacity of 741 mA h gZn-1 under 10 mA cm-2 . Rechargeable Zn-air
      batteries based on C-MOF-C2-900 as an ORR and OER bifunctional catalyst exhibit
      initial charge and discharge potentials at 1.81 and 1.28 V (2 mA cm-2 ), along
      with an excellent cycling stability with no increase in polarization even after
      120 h - outperform their counterparts based on noble-metal-based air electrodes.
      The resultant rechargeable Zn-air batteries are used to efficiently power
      electrochemical water-splitting systems, demonstrating promising potential as
      integrated green energy systems for practical applications.

PMID- 29349842
TI  - Is "end of life" a special case? Connecting Q with survey methods to measure
      societal support for views on the value of life-extending treatments.
AB  - Preference elicitation studies reporting societal views on the relative value of
      end-of-life treatments have produced equivocal results. This paper presents an
      alternative method, combining Q methodology and survey techniques (Q2S) to
      determine the distribution of 3 viewpoints on the relative value of end-of-life
      treatments identified in a previous, published, phase of this work. These were
      Viewpoint 1, "A population perspective: value for money, no special cases";
      Viewpoint 2, "Life is precious: valuing life-extension and patient choice"; and
      Viewpoint 3, "Valuing wider benefits and opportunity cost: the quality of life
      and death." A Q2S survey of 4,902 respondents across the United Kingdom measured
      agreement with these viewpoints; 37% most agreed with Viewpoint 1, 49% with
      Viewpoint 2, and 9% with Viewpoint 3. Regression analysis showed associations of
      viewpoints with gender, level of education, religion, voting preferences, and
      satisfaction with the NHS. The Q2S approach provides a promising means to
      investigate how in-depth views and opinions are represented in the wider
      population. As demonstrated in this study, there is often more than 1 viewpoint
      on a topic and methods that seek to estimate that averages may not provide the
      best guidance for societal decision-making.

PMID- 29349844
TI  - Exploration of joint working practices on anti-social behaviour between criminal
      justice, mental health and social care agencies: A qualitative study.
AB  - Although the police play an important role for people with mental health problems
      in the community, little is known about joint working practices between mental
      health, social care and police services. There is potential for tensions and
      negative outcomes for people with mental health problems, in particular when the
      focus is on behaviours that could be interpreted as anti-social. This study
      explores perceptions about joint working between mental health, social care and
      police services with regard to anti-social behaviour. We conducted a multi-method
      sequential qualitative study in the UK collecting data between April 2014 and
      August 2016. Data were collected from two study sites: 60 narrative police logs
      of routinely gathered information, and semi-structured interviews and focus
      groups with professionals from a range of statutory and third sector
      organisations (N = 55). Data sets were analysed individually, using thematic
      iterative coding before integrating the findings. We also looked at sequencing
      and turning points in the police logs. Findings mapped on a continuum of joint
      working practices, with examples more likely to be away from the policy ideal of
      partnership working as being central to mainstream activities. Joint working was
      driven by legal obligations and concerns about risk rather than a focus on the
      needs of a person with mental health problems. This was complicated by different
      perceptions of the police role in mental health. Adding anti-social behaviour to
      this mix intensified challenges as conceptualisation of the nature of the problem
      and agreeing on best practice and care is open to interpretations and judgements.
      Of concern is an evident lack of awareness of these issues. There is a need to
      reflect on joint working practices, including processes and goals, keeping in
      mind the health and welfare needs of people with mental health problems.

PMID- 29349843
TI  - Pregnancy after bariatric surgery: Maternal and fetal outcomes of 39 pregnancies
      and a literature review.
AB  - AIM: We aimed to evaluate the impact of bariatric surgery (BS) on maternal and
      fetal outcomes. METHODS: A retrospective, descriptive, observational study of 39
      pregnant women who underwent BS in our institution between 2010 and 2014 was
      carried out. A sample of women who became pregnant after BS was evaluated, based
      on data concerning pregnancy, childbirth, and newborns. RESULTS: Of the 1182
      patients who underwent BS at our institution during the study period, 1016
      (85.9%) were women. Thirty-nine of these women (with an average age of 31 +/- 4.8
      years) became pregnant (one twin pregnancy) and 29 of the 39 had undergone a
      gastric bypass. The mean time interval between BS and pregnancy was 16.6 +/- 4.8
      months; however, 16 (41%) women became pregnant less than a year after BS. The
      pre-BS body mass index (BMI) of the 39 women was 44.5 +/- 6.2 kg/m2 . The women
      had a mean BMI of 30.2 +/- 3.8 kg/m2 when they got pregnant and they gained 13.2
      +/- 7.3 kg during pregnancy. Iron deficiency was observed in 18 (46.1%) women, 16
      (45.7%) had vitamin B12 deficiency, 12 (66.8%) had zinc deficiency, and 20
      (60.6%) had vitamin D deficiency. Three women developed gestational diabetes
      mellitus. Premature rupture of membranes occurred in two pregnancies, preterm
      delivery in five, and there was one spontaneous abortion. Cesarean section was
      performed in seven cases. The average newborn weight was 3002 +/- 587 g, five
      were small for gestational age, and one had macrosomia. Three infants had to be
      admitted to an intensive care unit. CONCLUSION: Although pregnancy after BS is
      safe and well tolerated, close monitoring by a multidisciplinary team is required
      to evaluate complications resulting from BS, especially a deficit of
      micronutrients.

PMID- 29349845
TI  - Effects of intravenous tryptophan infusion on thermoregulation in steers exposed
      to acute heat stress.
AB  - This study was conducted to investigate the effect of tryptophan (TRP) supply on
      the thermoregulatory responses via brain serotonin (5-HT) in cattle. In period 1,
      12 Holstein steers were kept under a constant room temperature (22 degrees C) and
      were administered the intravenous (i.v.) infusion of saline or TRP (38.5 mg/kg/2
      h). Changes in rectal temperature (RT), 5-HT concentration in the cerebrospinal
      fluid (CSF), and other factors involved in thermoregulation were measured. In
      period 2, the steers received the same treatments as in period 1; however, the
      room temperature was elevated from 22 degrees C to 33 degrees C during i.v.
      infusion and maintained at 33 degrees C for 3 h. 5-HT concentration in CSF
      increased following TRP infusion in both periods, and RT significantly decreased
      following TRP infusion only in period 2. The effect of TRP on respiration rate
      and plasma prolactin and total triiodothyronine concentrations was not
      significant. These results suggest that increase in TRP supply can attenuate
      increase in RT in response to acute heat stress through the increase in brain 5
      HT, followed by presumable increase in evaporative heat loss from the skin
      surface in cattle. It is possible that the increase in peripheral blood TRP
      metabolites could also participate in the hypothermic effect of TRP.

PMID- 29349846
TI  - Preparation of dummy template-imprinted polymers for the rapid extraction of
      nonsteroidal anti-inflammatory drugs residues in aquatic environmental samples.
AB  - A molecularly imprinted polymer was synthesized and applied as a sorbent in the
      solid-phase extraction device. The imprinted polymer was characterized by fourier
      transform infrared spectroscopy and scanning electron microscope. The results
      revealed that imprinted polymer possess sensitive selectivity and reliable
      adsorption properties for five NSAIDs. The imprinted polymer was successfully
      applied to the pre-concentration for five NSAIDs in different water samples prior
      to UPLC-MS/MS. In the early studies, several factors were investigated, including
      pH adjustment, the kind of elution solvent and the volume of elution solvent.
      Finally, we found that the pH 5 and an aliquot of 2 mL methanol were suitable for
      the water samples. The limits of detection and limits of quantitation of five
      nonsteroidal anti-inflammatory drugs varied from 0.007 to 0.480 MUg L-1 and 0.03
      to 1.58 MUg L-1 , respectively. The spiking recoveries of the target analytes
      were 50.33-127.64% at the levels of 0.2 MUg L-1 , 2 MUg L-1 and 5 MUg L-1 . The
      precision and accuracy of this method showed a great increase compared with
      traditional solid-phase extraction. The developed method was successfully applied
      to extraction and analysis of NSAIDs in different water samples with satisfactory
      results which could help us better understand their environmental fate and risk
      to ecological health.

PMID- 29349847
TI  - Increased pain sensitivity in migraine and tension-type headache coexistent with
      low back pain: A cross-sectional population study.
AB  - BACKGROUND: Low back pain is common in the general population and in individuals
      with primary headaches. We assessed the relative frequency of self-reported back
      pain in persons with and without primary headaches and examined pain sensitivity.
      METHOD: A population of 796 individuals completed a headache interview based on
      ICHD criteria and provided data of interest in a self-administered questionnaire.
      Headache cases were classified into chronic (>=15) (CH) or episodic (<15 headache
      days/month) (EH). A total of 495 had a pericranial total tenderness score (TTS),
      and 494 had cephalic and extracephalic pressure pain thresholds (PPTs) assessed.
      RESULTS: Adjusted for age, gender, education and poor self-rated health, 1-year
      relative frequency of back pain was higher in individuals with CH (82.5%) and EH
      (80.1%) compared to no headache group (65.7%). In persons with back pain, TTS was
      higher in CH, (26.3 +/- 12.1) than in EH, (18.5 +/- 10.0; p < 0.001) and higher
      in both groups than in those with no headache, 10.8 +/- 8.5 (p < 0.001 and p <
      0.001, respectively). In persons with back pain, temporalis PPT were lower in CH,
      169.3 +/- 57.8, than in EH, 225.2 +/- 98.1, and in no headache group, 244.3 +/-
      105.4 (p = 0.02 and p = 0.01, respectively). In persons with back pain, finger
      PPT were lower in CH, 237.1 +/- 106.7, than in EH, 291.3 +/- 141.3, or in no
      headache group, 304.3 +/- 137.4 (p = 0.02 and p < 0.001, respectively).
      CONCLUSION: Back pain is highly frequent in individuals with CH, followed by EH
      and no headache. In persons with CH, back pain is associated with lower cephalic
      and extracephalic PPTs suggesting central sensitization may be a substrate or
      consequence of comorbidity. SIGNIFICANCE: We found that back pain has high
      relative frequency in individuals with CH followed EH and no headache. Back pain
      is associated with low cephalic and extracephalic PPTs in individuals with CH.
      Central sensitization may be a substrate or consequence of this comorbidity of
      back pain and CH.

PMID- 29349848
TI  - Evaluation of the stability and stratification of propofol and ketamine mixtures
      for pediatric anesthesia.
AB  - BACKGROUND: The combination of propofol and ketamine is commonly used for total
      intravenous anesthesia. These drugs can be delivered in different syringes or in
      the same syringe. We hypothesized that the drugs might separate and different
      concentrations of each drug could be found in different parts of the syringe
      during the procedure period when they were mixed in 1 syringe. METHODS: Twelve 60
      mL polypropylene syringes were prepared by mixing propofol and ketamine as 4
      groups on the basis of propofol/ketamine mixture ratios (5:1 and 6.7:1) and
      propofol solution concentrations. Syringes were placed upright in the vertical
      position into a rack and kept at room temperature (21.5-22.5 degrees C), in
      daylight conditions and were not moved for 360 minutes. Samples of the mixture
      were taken from both the top and the bottom of the syringe. The first 1 mL of the
      samples was discarded, the following second 1 mL of the samples was filtered
      using 0.2-MUm polytetrafluoroethylene filters and measured twice (n = 6). Samples
      were taken at the following time intervals: T0, T10, T30, T60, T90, T120, T180,
      T240, T300, and T360 min. Syringes were checked visually for any color change and
      separation lines between the drugs. RESULTS: There were no significant
      differences between the propofol and ketamine concentrations of the top and
      bottom samples in all 4 groups. In addition, there were no statistically
      significant changes of propofol and ketamine concentrations of samples over 360
      minutes in any of the 4 groups. No visual changes were observed during 6 hours'
      observation. CONCLUSION: The results of our measurements demonstrated that
      mixtures of propofol (1% and 2%) and ketamine at 5:1 and 6.7:1 ratios could be
      used in terms of mixture homogeneity and stability in a polypropylene syringe
      during a 6-hour period at room temperature.

PMID- 29349849
TI  - The optimal intestinal segment length for experimental size-mismatched intestinal
      transplantation: Defining the maximum length with the lowest blood flow needs in
      a porcine model.
AB  - Transplanted Intestinal Segments (IS) must match the perfusion capacities of the
      recipient. This can be challenging during a size-mismatched SBTX. In this study,
      we defined the maximum IS length with lowest blood flow needs in a porcine model
      by evaluating the physiological perfusion rates of different IS lengths. Blood
      flow in the SMA, aorta segment four, and general circulatory parameters were
      monitored before and after sequential intestinal resection. IS lengths of 30 cm,
      60 cm, 120 cm, and 300 cm (n = 8 each) were compared. The IS blood flow
      requirements increased with IS length (30 cm: 19.5 +/- 3.4 mL/min; 60 cm: 16.9 +/
      6.7 mL/min; 120 cm: 34.9 +/- 8.5 mL/min; 300 cm: 62.9 +/- 11.6 mL/min). Absolute
      IS blood flow (P = .004), percentage IS blood flow uptake from the SMA (P =
      .001), and percentage IS blood flow uptake from the aorta (P = .005) increased
      significantly between 60 cm and 120 cm. We concluded that 60 cm was the maximum
      IS length before blood flow demands significantly increased in a porcine model.

PMID- 29349850
TI  - Reconstructing geographical parthenogenesis: effects of niche differentiation and
      reproductive mode on Holocene range expansion of an alpine plant.
AB  - Asexual taxa often have larger ranges than their sexual progenitors, particularly
      in areas affected by Pleistocene glaciations. The reasons given for this
      'geographical parthenogenesis' are contentious, with expansion of the ecological
      niche or colonisation advantages of uniparental reproduction assumed most
      important in case of plants. Here, we parameterized a spread model for the alpine
      buttercup Ranunculus kuepferi and reconstructed the joint Holocene range
      expansion of its sexual and apomictic cytotype across the European Alps under
      different simulation settings. We found that, rather than niche broadening or a
      higher migration rate, a shift of the apomict's niche towards colder conditions
      per se was crucial as it facilitated overcoming of topographical barriers, a
      factor likely relevant for many alpine apomicts. More generally, our simulations
      suggest potentially strong interacting effects of niche differentiation and
      reproductive modes on range formation of related sexual and asexual taxa arising
      from their differential sensitivity to minority cytotype disadvantage.

PMID- 29349851
TI  - Clinical and molecular implications of structural changes to desmosomes and
      corneodesmosomes.
AB  - Desmosomes provide the main intercellular adhesive properties between epidermal
      keratinocytes. Their distribution becomes uneven in severe dermatitis, multiple
      allergies and metabolic wasting syndrome due to desmoglein 1 deficiency and the
      loss of intercellular adhesion or acantholysis. When keratinocytes differentiate
      from granular cells into cornified cells, desmosomes are transformed into
      corneodesmosomes and can provide stronger intercellular adhesion. Degradation of
      corneodesmosomes is a tightly regulated process involving a number of proteases
      and their inhibitors. Peripheral corneodesmosomes are protected from proteolytic
      degradation by the tight junction-related structures around them, and this
      construction provides the basis for the normal basket weave-like structure of the
      stratum corneum. In Netherton syndrome, which is caused by an absence of the
      protease inhibitor lymphoepithelial Kazal-type-related inhibitor, premature
      degradation of corneodesmosomes occurs due to the overactivation of proteases
      involved in corneodesmosome degradation. Inflammatory peeling skin disease is
      caused by the absence of corneodesmosin, a unique component of corneodesmosomes.
      In this disease, corneodesmosomes are structurally abnormal, and their
      adhesiveness is compromised, which leads to intercellular splitting between the
      stratum corneum and stratum granulosum. The better we understand desmosome and
      corneodesmosome ultrastructure in normal and diseased skin, the clearer the
      physiological and pathological mechanisms of epidermal integrity become.

PMID- 29349852
TI  - What really matters to people with aphasia when it comes to group work? A
      qualitative investigation of factors impacting participation and integration.
AB  - BACKGROUND: Participation in a group environment is an inherently complex
      undertaking for people with aphasia. It involves engaging in multi-person
      interactions with other people who may have a range of communication strengths
      and strategies at their disposal. The potential challenges of community aphasia
      group participation and practice has had limited attention in the research
      literature. Evidence from group users have primarily been drawn from the
      perspective of long-term members or those participating in highly specific and
      time-bound groups. There is a need to explore the experiences of a broader
      sample, including people who have left groups, to improve our understanding of
      structures, processes as well as leadership behaviours that may facilitate
      positive group participation experiences. AIM: To examine the potential factors
      operating within the group environment that contribute to positive and negative
      participation experiences. METHODS & PROCEDURES: Twenty-two people with aphasia
      participated in semi-structured interviews about their experiences of community
      aphasia groups. People who maintained long-term membership as well as those who
      had left groups were sampled. An interpretative phenomenological framework was
      employed to examine the data collected. OUTCOMES & RESULTS: Seven factors emerged
      as central to participation experiences and contributed to the ability of people
      with aphasia to integrate and engage in the group space. These factors included:
      (1) balanced interactional patterns; (2) an open and non-hierarchical group
      environment; (3) communication awareness and education amongst members; (4)
      meaningful activity; (5) ritual and structure; (6) composition and group size;
      and (7) group leadership. CONCLUSIONS & IMPLICATIONS: People with aphasia
      perceive community aphasia-group participation to be beneficial to their ability
      to live well with aphasia. However, a range of challenges to successful
      participation are also evident. Inputs such as peer-to-peer communication
      strategies, shared roles and responsibilities, and consultation with regard to
      group objectives and processes provide group members with the opportunity to
      become active contributors, demonstrate competence and have influence over the
      group. When inputs are poorly implemented or absent, people with aphasia are at
      risk of feeling disabled and marginalized by the group experience.

PMID- 29349853
TI  - Piezotronic Tuning of Potential Barriers in ZnO Bicrystals.
AB  - Coupling of magnetic, ferroelectric, or piezoelectric properties with charge
      transport at oxide interfaces provides the option to revolutionize classical
      electronics. Here, the modulation of electrostatic potential barriers at tailored
      ZnO bicrystal interfaces by stress-induced piezoelectric polarization is
      reported. Specimen design by epitaxial solid-state transformation allows for both
      optimal polarization vector alignment and tailoring of defect states at a
      semiconductor-semiconductor interface. Both quantities are probed by transmission
      electron microscopy. Consequently, uniaxial compressive stress affords a complete
      reduction of the potential barrier height at interfaces with head-to-head
      orientation of the piezoelectric polarization vectors and an increase in
      potential barrier height at interfaces with tail-to-tail orientation. The
      magnitude of this coupling between mechanical input and electrical transport
      opens pathways to the design of multifunctional electronic devices like strain
      triggered transistors, diodes, and stress sensors with feasible applications for
      human-computer interfacing.

PMID- 29349854
TI  - Implementing health and social care integration in Scotland: Renegotiating new
      partnerships in changing cultures of care.
AB  - Health and social care integration has been a long-term goal for successive
      governments in Scotland, culminating in the implementation of the recent Public
      Bodies (Joint Working) Scotland Act 2014. This laid down the foundations for the
      delegation of health and social care functions and resources to newly formed
      Integrated Joint Boards. It put in place demands for new ways of working and
      partnership planning. In this article, we explore the early implementation of
      this Act and how health and social care professionals and the third sector have
      begun to renegotiate their roles. The paper draws on new empirical data collated
      through focus groups and interviews with over 70 professionals from across
      Scotland. The data are explored through the following key themes: changing
      cultures, structural imbalance, governance and partnership and the role of
      individuals or "boundary spanners" in implementing change. We also draw on
      evidence from other international systems of care, which have implemented
      integration policies, documenting what works and what does not. We argue that
      under the current framework much of the potential for integration is not being
      fulfilled and that the evidence suggests that at this early stage of roll-out,
      the structural and cultural policy changes that are required to enable this
      policy shift have not yet emerged. Rather, integration has been left to
      individual innovators or "boundary spanners" and these are acting as key drivers
      of change. Where change is occurring, this is happening despite the system. As it
      is currently structured, we argue that too much power is in the hands of health
      and despite the rhetoric of partnership working, there are real structural
      imbalances that need to be reconciled.

PMID- 29349855
TI  - Understanding remote Aboriginal drug and alcohol residential rehabilitation
      clients: Who attends, who leaves and who stays?
AB  - INTRODUCTION AND AIMS: Aboriginal residential rehabilitation services provide
      healing for Aboriginal people who misuse substances. There is limited available
      research that empirically describes client characteristics of these services.
      This study examined 5 years of data of a remote Aboriginal residential
      rehabilitation service. DESIGN AND METHODS: Retrospective analysis of 329 client
      admissions to Orana Haven Drug and Alcohol Rehabilitation Centre from 2011 to
      2016. Multinomial and binary logistic regressions were conducted to identify
      trends in the data. RESULTS: There were 66 admissions recorded annually, of which
      most identified as Aboriginal (85%). Mean length of stay was 56 days, with one in
      three (36%) discharging within the first month. A third (32%) completed, 47% self
      discharged and 20% house-discharged from the program. Client age significantly
      increased over time (P = 0.03), with most aged from 26 to 35. Older clients were
      significantly more likely to readmit (P < 0.002) and stay longer than 90 days (P
      = 0.02). Most clients were referred from the criminal justice system,
      significantly increasing from 79% (2011-2012) to 96% (2015-2016) (P < 0.001) and
      these clients were more likely to self-discharge (P < 0.01). Among a subset of
      clients, most (69%) reported concerns with polysubstance use and half (51%)
      reported mental illness. DISCUSSION AND CONCLUSIONS: The current study makes a
      unique contribution to the literature by empirically describing the
      characteristics of clients of a remote Aboriginal residential rehabilitation
      service to more accurately tailor the service to the client's needs. Key
      recommendations include integrating these empirical observations with staff and
      client perceptions to co-design a model of care, standardise data collection, and
      routinely following-up clients to monitor treatment effectiveness.

PMID- 29349856
TI  - Self-responsibility, rationing and treatment decision making - managing moral
      narratives alongside fiscal reality in the obesity surgery clinic.
AB  - BACKGROUND: Addressing the prevalence of severe obesity and its concomitant
      morbidities is widely acknowledged as one of the most pressing global health
      priorities. Nevertheless, a paucity of effective interventions and universal
      pressure on health-care budgets means that access to obesity treatments is often
      limited. Although health-care rationing can be conceived as a socially
      constructed process, little is known about how decisions emerge within the
      context of face-to-face doctor-patient interactions. METHODS: In this study, we
      used in-depth interviews and clinic observations to investigate clinicians' (n =
      11) and patients' (n = 22) experiences of the rationing of obesity surgery and to
      examine how broader cultural assumptions around personal responsibility for
      health emerged in the context of clinical interactions. RESULTS: Patients and
      clinicians worked within similar frameworks when it came to self-responsibility
      for health and the appropriateness of providing publicly-funded weight loss
      surgery. Issues around personal accountability dominated consultations, and
      patients were expected to provide narratives of the development of their obesity
      and to account for the failure of previous interventions. Clinicians faced the
      added pressure of having to prioritise a limited number of patients for surgery,
      which was predominantly managed through mandating pre-referral weight loss
      targets. DISCUSSION: Although clinicians sought to maintain an empathic attitude
      towards individual patients, in practice they were conflicted by their
      responsibility to ration health-care resources and tended to rely on entrenched
      models of behaviour change to allocate treatment. As a result, the content of
      consultations was mostly focused on issues of personal responsibility, reflecting
      wider stigmatized attitudes towards extreme obesity.

PMID- 29349858
TI  - Efficient, Hysteresis-Free, and Stable Perovskite Solar Cells with ZnO as
      Electron-Transport Layer: Effect of Surface Passivation.
AB  - The power conversion efficiency of perovskite solar cells (PSCs) has ascended
      from 3.8% to 22.1% in recent years. ZnO has been well-documented as an excellent
      electron-transport material. However, the poor chemical compatibility between ZnO
      and organo-metal halide perovskite makes it highly challenging to obtain highly
      efficient and stable PSCs using ZnO as the electron-transport layer. It is
      demonstrated in this work that the surface passivation of ZnO by a thin layer of
      MgO and protonated ethanolamine (EA) readily makes ZnO as a very promising
      electron-transporting material for creating hysteresis-free, efficient, and
      stable PSCs. Systematic studies in this work reveal several important roles of
      the modification: (i) MgO inhibits the interfacial charge recombination, and thus
      enhances cell performance and stability; (ii) the protonated EA promotes the
      effective electron transport from perovskite to ZnO, further fully eliminating
      PSCs hysteresis; (iii) the modification makes ZnO compatible with perovskite,
      nicely resolving the instability of ZnO/perovskite interface. With all these
      findings, PSCs with the best efficiency up to 21.1% and no hysteresis are
      successfully fabricated. PSCs stable in air for more than 300 h are achieved when
      graphene is used to further encapsulate the cells.

PMID- 29349859
TI  - Re: Peripartum hysterectomy: an economic analysis of direct healthcare costs
      using routinely collected data: Some concerns from obstetricians' viewpoint.

PMID- 29349857
TI  - A Diazido Mannose Analogue as a Chemoenzymatic Synthon for Synthesizing Di-N
      acetyllegionaminic Acid-Containing Glycosides.
AB  - A chemoenzymatic synthon was designed to expand the scope of the chemoenzymatic
      synthesis of carbohydrates. The synthon was enzymatically converted into
      carbohydrate analogues, which were readily derivatized chemically to produce the
      desired targets. The strategy is demonstrated for the synthesis of glycosides
      containing 7,9-di-N-acetyllegionaminic acid (Leg5,7Ac2 ), a bacterial nonulosonic
      acid (NulO) analogue of sialic acid. A versatile library of alpha2-3/6-linked
      Leg5,7Ac2 -glycosides was built by using chemically synthesized 2,4-diazido-2,4,6
      trideoxymannose as a chemoenzymatic synthon for highly efficient one-pot
      multienzyme (OPME) sialylation followed by downstream chemical conversion of the
      azido groups into acetamido groups. The syntheses required 10 steps from
      commercially available d-fucose and had an overall yield of 34-52 %, thus
      representing a significant improvement over previous methods. Free Leg5,7Ac2
      monosaccharide was also synthesized by a sialic acid aldolase-catalyzed reaction.

PMID- 29349860
TI  - Effects of maternal anthropometrics on pregnancy outcomes in South Asian women: a
      systematic review.
AB  - AIM: This systematic review investigates associations between maternal pre
      pregnancy/early-pregnancy anthropometrics (e.g. weight and body fat),
      anthropometric change and pregnancy outcomes in South Asian and White women.
      METHODS: Twelve electronic literature databases, reference lists and citations of
      all included studies were searched. Observational studies published in the
      English language were included. Descriptive synthesis was used to summarize the
      evidence base. RESULTS: Twenty-two studies met the inclusion criteria (403,609
      births [351,856 White and 51,753 South Asian]). Nine were prospective cohort
      studies, nine were retrospective cohort studies and two were cross-sectional
      studies. Results suggested that in South Asian women, maternal pre
      pregnancy/early-pregnancy anthropometrics were associated with anthropometric
      change, birthweight, mode of delivery and gestational diabetes mellitus (GDM).
      Gestational anthropometric change was found to be associated with GDM. There was
      limited evidence to suggest that there may be associations between maternal pre
      anthropometrics/early anthropometrics and hypertensive disorders, stillbirth,
      congenital anomalies, post-natal weight retention and post-natal impaired glucose
      tolerance. The evidence suggested a combined effect of pre-pregnancy/early
      pregnancy anthropometrics and gestational anthropometric change on both GDM and
      post-natal weight retention. CONCLUSION: The increased risk of adverse pregnancy
      outcomes in South Asian women should be considered in guidelines for weight
      management before and during pregnancy.

PMID- 29349861
TI  - Validated UPLC-MS/MS method for quantification of seven compounds in rat plasma
      and tissues: Application to pharmacokinetic and tissue distribution studies in
      rats after oral administration of extract of Eclipta prostrata L.
AB  - A rapid, sensitive and specific ultra-high-performance liquid chromatography
      coupled with tandem mass spectrometry (UPLC-MS/MS) method was developed to
      investigate the pharmacokinetics and tissue distribution of Eclipta prostrata
      extract. Rats were orally administrated the 70% ethanol extract of E. prostrata,
      and their plasma as well as various organs were collected. The concentrations of
      seven main compounds, ecliptasaponin IV, ecliptasaponin A, apigenin, 3'
      hydroxybiochanin A, luteolin, luteolin-7-O-glucoside and wedelolactone, were
      quantified by UPLC-MS/MS through multiple reactions monitoring method. The
      precisions (RSD) of the analytes were all <15.00%. The extraction recoveries
      ranged from 74.65 to 107.45% with RSD <= 15.36%. The matrix effects ranged from
      78.00 to 118.06% with RSD <= 15.04%. To conclude, the present pharmacokinetic and
      tissue distribution studies provided useful information for the clinical usage of
      Eclipta prostrata L.

PMID- 29349862
TI  - Implementing managed alcohol programs in hospital settings: A review of academic
      and grey literature.
AB  - ISSUES: People with severe alcohol use disorders are at increased risk of poor
      acute-care outcomes, in part due to difficulties maintaining abstinence from
      alcohol while hospitalised. Managed alcohol programs (MAP), which administer
      controlled doses of beverage alcohol to prevent withdrawal and stabilise drinking
      patterns, are one strategy for increasing adherence to treatment, and improving
      health outcomes for hospital inpatients with severe alcohol use disorders.
      APPROACH: Minimal research has examined the implementation of MAPs in hospital
      settings. We conducted a scoping review to describe extant literature on MAPs in
      community settings, as well as the therapeutic provision of alcohol to hospital
      inpatients, to assess the feasibility of implementing formal MAPs in hospital
      settings and identify knowledge gaps requiring further study. Four academic and
      10 grey literature databases were searched. Evidence was synthesised using
      quantitative and qualitative approaches. KEY FINDINGS: Forty-two studies met
      review inclusion criteria. Twenty-eight examined the administration of alcohol to
      hospital inpatients, with most reporting positive outcomes related to prevention
      or treatment of alcohol withdrawal. Fourteen studies examined MAPs in the
      community and reported that they help stabilise drinking patterns, reduce alcohol
      related harms and facilitate non-judgemental health and social care.
      IMPLICATIONS/CONCLUSIONS: MAPs in the community have been well described and
      research has documented effective provision of alcohol in hospital settings for
      addressing withdrawal. Implementing MAPs as a harm reduction approach in hospital
      settings is potentially feasible. However, there remains a need to build off
      extant literature and develop and evaluate standardised MAP protocols tailored to
      acute-care settings.

PMID- 29349863
TI  - Experimental Observation of Thermally Excited Triplet States of Heavier Group 15
      Element Centered Diradical Dianions.
AB  - One-electron reductions of Mes*As=Fl* (1; Fl*=2,7-di-tert-butylfluorenylidene,
      Mes*=2,4,6-tBu3 C6 H2 ) and diarsaalkenes [1,2-b]-IF(=AsMes*)2 (2;
      IF=indenofluorene) with potassium led to the isolation of the arsenic-centered
      radical anion salts 1K and 2K, respectively. The diradical dianion salts 2K2 and
      3K2 were afforded by the reduction of 2 and 2,8-tBu2 -[2,1-b]-IF(=AsMes*)2 (3)
      with an excess amount of KC8 . The radicals have been investigated by single
      crystal X-ray crystallography, EPR, and UV/Vis absorption spectroscopy, along
      with theoretical calculations. The calculations revealed that 2K2 and 3K2 feature
      open-shell singlet ground states with singlet-triplet energy gaps of 2.1 and 1.0
      kcal mol-1 , respectively. They are readily thermally excited to triplet states
      as demonstrated by EPR spectroscopy. The obtained diradicals represent the first
      examples of heavier Group 15 element centered diradicals with experimentally
      observable triplet states.

PMID- 29349865
TI  - Superfast Room-Temperature Activation of SnO2 Thin Films via Atmospheric Plasma
      Oxidation and their Application in Planar Perovskite Photovoltaics.
AB  - The power conversion efficiency (PCE) of perovskite solar cells (PSCs) has now
      exceeded 20%; thus, research focus has shifted to establishing the foundations
      for commercialization. One of the pivotal themes is to curtail the overall
      fabrication time, to reduce unit cost, and mass-produce PSCs. Additionally,
      energy dissipation during the thermal annealing (TA) stage must be minimized by
      realizing a genuine low-temperature (LT) process. Here, tin oxide (SnO2 ) thin
      films (TFs) are formulated at extremely high speed, within 5 min, under an almost
      room-temperature environment (<50  degrees C), using atmospheric Ar/O2 plasma
      energy (P-SnO2 ) and are applied as an electron transport layer of a "n-i-p"-type
      planar PSC. Compared with a thermally annealed SnO2 TF (T-SnO2 ), the P-SnO2 TF
      yields a more even surface but also outstanding electrical conductivity with
      higher electron mobility and a lower number of charge trap sites, consequently
      achieving a superior PCE of 19.56% in P-SnO2 -based PSCs. These findings motivate
      the use of a plasma strategy to fabricate various metal oxide TFs using the sol
      gel route.

PMID- 29349866
TI  - Amorphous Materials for Enhanced Localized Surface Plasmon Resonances.
AB  - The discovery of localized surface plasmon resonance (LSPR) in semiconductor
      nanocrystals has initiated a new field in plasmonics. Plasmonic nanocrystals in
      particular have seen rapid development in recent years because they are a class
      of materials with unique photoelectronic properties. At present, a growing number
      of amorphous plasmonic materials has been steadily capturing scientific interest,
      though only a few of these are well characterized. Here we focus on recent
      developments in state-of-the art experiments and explore the vast library of
      plasmonic properties in amorphous materials, including their application fields
      and optical spectral range. Taken together, the growing regime of amorphous
      material plasmonics offers enticing avenues for harnessing light-matter
      interactions from the visible to the terahertz region, with new potential for
      optical manipulation beyond what can be accomplished using traditional crystal
      materials.

PMID- 29349867
TI  - Volumetric modulated arc therapy treatment planning of thoracic vertebral
      metastases using stereotactic body radiotherapy.
AB  - PURPOSE/OBJECTIVES: To retrospectively evaluate the plan quality, treatment
      efficiency, and accuracy of volumetric modulated arc therapy (VMAT) plans for
      thoracic spine metastases using stereotactic body radiotherapy (SBRT).
      MATERIALS/METHODS: Seven patients with thoracic vertebral metastases treated with
      noncoplanar hybrid arcs (NCHA) (1 to 2 3D-conformal partial arcs +7 to 9 IMRT
      beams) were re-optimized with VMAT plans using three coplanar arcs. Tumors were
      located between T2 and T7 and PTVs ranged between 24.3 and 240.1 cc (median 48.1
      cc). All prescriptions were 30 Gy in 5 fractions with 6 MV beams treated using
      the Novalis Tx linac equipped with high definition multileaf collimators (HDMLC).
      MR images were fused with planning CTs for target and OAR contouring. Plans were
      compared for target coverage using conformality index (CI), homogeneity index
      (HI), D90, D98, D2, and Dmedian. Normal tissue sparing was evaluated by comparing
      doses to the spinal cord (Dmax, D0.35, and D1.2 cc), esophagus (Dmax and D5 cc),
      heart (Dmax, D15 cc), and lung (V5 and V10). Data analysis was performed with a
      two-sided t-test for each set of parameters. Dose delivery efficiency and
      accuracy of each VMAT plan was assessed via quality assurance (QA) using a
      MapCHECK device. The Beam-on time (BOT) was recorded, and a gamma index was used
      to compare dose agreement between the planned and measured doses. RESULTS: VMAT
      plans resulted in improved CI (1.02 vs. 1.36, P = 0.05), HI (0.14 vs. 0.27, P =
      0.01), D98 (28.4 vs. 26.8 Gy, P = 0.03), D2 (32.9 vs. 36.0 Gy, P = 0.02), and
      Dmedian (31.4 vs. 33.7 Gy, P = 0.01). D90 was improved but not statistically
      significant (30.4 vs. 31.0 Gy, P = 0.38). VMAT plans showed statistically
      significant improvements in normal tissue sparing: Esophagus Dmax (22.5 vs. 27.0
      Gy, P = 0.03), Esophagus 5 cc (17.6 vs. 21.5 Gy, P = 0.02), and Heart Dmax (13.1
      vs. 15.8 Gy, P = 0.03). Improvements were also observed in spinal cord and lung
      sparing as well but were not statistically significant. The BOT showed
      significant reduction for VMAT, 4.7 +/- 0.6 min vs. 7.1 +/- 1 min for NCHA (not
      accounting for couch kicks). VMAT plans demonstrated an accurate dose delivery of
      95.5 +/- 1.0% for clinical gamma passing rate of 3%/3 mm criteria, which was
      similar to NCHA plans. CONCLUSIONS: VMAT plans have shown improved dose
      distributions and normal tissue sparing compared to NCHA plans. Significant
      reductions in treatment time could potentially minimize patient discomfort and
      intrafraction movement errors. VMAT planning for SBRT is an attractive option for
      the treatment of metastases to thoracic vertebrae, and further investigation
      using alternative fractionation schedules is warranted.

PMID- 29349868
TI  - Workplace alcohol harm reduction intervention in Australia: Cluster non
      randomised controlled trial.
AB  - INTRODUCTION AND AIMS: The workplace holds substantial potential as an alcohol
      harm reduction and prevention setting. Few studies have rigorously examined
      strategies to reduce workplace alcohol-related harm. Hence, an in-situ 3 year
      trial of a comprehensive alcohol harm reduction intervention in Australian
      manufacturing workplaces was undertaken. DESIGN AND METHODS: Informed by a gap
      analysis, a multi-site trial was undertaken. Three manufacturing industry
      companies, located at four separate worksites, with a minimum of 100 employees
      were recruited through a local industry network. Based on worksite location, two
      worksites were allocated to the intervention group and two to the comparison
      group. The pre-specified primary outcome measure, risky drinking (Alcohol Use
      Disorders Identification Test, AUDIT-C) and other self-report measures were
      collected pre-intervention (T1), 12 months (T2) and 24 months post-intervention
      (T3). RESULTS: No significant intervention effect was observed for the primary
      outcome measure, risky drinking. Significant intervention effects were observed
      for increased awareness of alcohol policy and employee assistance. At T3, the
      odds of intervention group participants being aware of the workplace policy and
      aware of employee assistance were 48.9% (95% confidence interval 29.3-88.9%) and
      79.7% (11.5%, 91.8%), respectively, greater than comparison group participants.
      DISCUSSION AND CONCLUSIONS: Comprehensive tailored workplace interventions can be
      effective in improving workplace alcohol policy awareness. This is one of few
      workplace alcohol trials undertaken to-date and the findings make an important
      contribution to the limited evidence base for workplace alcohol harm prevention
      initiatives.

PMID- 29349864
TI  - The morphometric co-atrophy networking of schizophrenia, autistic and obsessive
      spectrum disorders.
AB  - By means of a novel methodology that can statistically derive patterns of co
      alterations distribution from voxel-based morphological data, this study analyzes
      the patterns of brain alterations of three important psychiatric spectra-that is,
      schizophrenia spectrum disorder (SCZD), autistic spectrum disorder (ASD), and
      obsessive-compulsive spectrum disorder (OCSD). Our analysis provides five
      important results. First, in SCZD, ASD, and OCSD brain alterations do not
      distribute randomly but, rather, follow network-like patterns of co-alteration.
      Second, the clusters of co-altered areas form a net of alterations that can be
      defined as morphometric co-alteration network or co-atrophy network (in the case
      of gray matter decreases). Third, within this network certain cerebral areas can
      be identified as pathoconnectivity hubs, the alteration of which is supposed to
      enhance the development of neuronal abnormalities. Fourth, within the
      morphometric co-atrophy network of SCZD, ASD, and OCSD, a subnetwork composed of
      eleven highly connected nodes can be distinguished. This subnetwork encompasses
      the anterior insulae, inferior frontal areas, left superior temporal areas, left
      parahippocampal regions, left thalamus and right precentral gyri. Fifth, the co
      altered areas also exhibit a normal structural covariance pattern which overlaps,
      for some of these areas (like the insulae), the co-alteration pattern. These
      findings reveal that, similarly to neurodegenerative diseases, psychiatric
      disorders are characterized by anatomical alterations that distribute according
      to connectivity constraints so as to form identifiable morphometric co-atrophy
      patterns.

PMID- 29349869
TI  - Clostridium difficile infection is associated with graft loss in solid organ
      transplant recipients.
AB  - Clostridium difficile infection (CDI) is a leading cause of infectious diarrhea
      in solid organ transplant recipients (SOT). We aimed to assess incidence, risk
      factors, and outcome of CDI within the Swiss Transplant Cohort Study (STCS). We
      performed a case-control study of SOT recipients in the STCS diagnosed with CDI
      between May 2008 and August 2013. We matched 2 control subjects per case by age
      at transplantation, sex, and transplanted organ. A multivariable analysis was
      performed using conditional logistic regression to identify risk factors and
      evaluate outcome of CDI. Two thousand one hundred fifty-eight SOT recipients,
      comprising 87 cases of CDI and 174 matched controls were included. The overall
      CDI rate per 10 000 patient days was 0.47 (95% confidence interval ([CI] 0.38
      0.58), with the highest rate in lung (1.48, 95% CI 0.93-2.24). In multivariable
      analysis, proven infections (hazard ratio [HR] 2.82, 95% CI 1.29-6.19) and
      antibiotic treatments (HR 4.51, 95% CI 2.03-10.0) during the preceding 3 months
      were independently associated with the development of CDI. Despite mild clinical
      presentations, recipients acquiring CDI posttransplantation had an increased risk
      of graft loss (HR 2.24, 95% CI 1.15-4.37; P = .02). These findings may help to
      improve the management of SOT recipients.

PMID- 29349870
TI  - Drug Dosing in Pregnant Women: Challenges and Opportunities in Using
      Physiologically Based Pharmacokinetic Modeling and Simulations.
AB  - The unmet medical need of providing evidence-based pharmacotherapy for pregnant
      women is recognized by the regulatory bodies. Physiologically based
      pharmacokinetic (PBPK) modeling offers an attractive platform to quantify
      anticipated changes in the pharmacokinetics (PKs) of drugs during pregnancy.
      Recent publications applying a pregnancy PBPK module to the prediction of
      maternal and fetal exposure of drugs are summarized. Future opportunities to use
      PBPK models to predict breast milk exposure and assess human fetotoxicity risks
      are presented.

PMID- 29349871
TI  - DSP30 and interleukin-2 as a mitotic stimulant in B-cell disorders including
      those with a low disease burden.
AB  - Chromosome abnormalities detected during cytogenetic investigations for B-cell
      malignancy offer prognostic information that can have wide ranging clinical
      impacts on patients. These impacts may include monitoring frequency, treatment
      type, and disease staging level. The use of the synthetic oligonucleotide DSP30
      combined with interleukin 2 (IL2) has been described as an effective mitotic
      stimulant in B-cell disorders, not only in chronic lymphocytic leukemia (CLL) but
      also in a range of other B-cell malignancies. Here, we describe the comparison of
      two B-cell mitogens, lipopolysaccharide (LPS), and DSP30 combined with IL2 as
      mitogens in a range of common B-cell disorders excluding CLL. The results showed
      that DSP30/IL2 was an effective mitogen in mature B-cell disorders, revealing
      abnormal cytogenetic results in a range of B-cell malignancies. The abnormality
      rate increased when compared to the use of LPS to 64% (DSP30/IL2) from 14% (LPS).
      In a number of cases the disease burden was proportionally very low, less than
      10% of white cells. In 37% of these cases, the DSP30 culture revealed abnormal
      results. Importantly, we also obtained abnormal conventional cytogenetics results
      in 3 bone marrow cases in which immunophenotyping showed an absence of an
      abnormal B-cell clone. In these cases, the cytogenetics results correlated with
      the provisional diagnosis and altered their staging level. The use of DSP30 and
      IL2 is recommended for use in many B-cell malignancies as an effective mitogen
      and their use has been shown to enable successful culture of the malignant clone,
      even at very low levels of disease.

PMID- 29349872
TI  - The personal communities of men experiencing later life widowhood.
AB  - Increasingly men are becoming widowed in later life due in part to a longer life
      expectancy. Social networks and social support are thought to help buffer the
      negative consequences of such later life transitions. This paper explores the
      personal communities of a group of older men experiencing widowhood. Qualitative
      in-depth interviews were conducted, September 2013-February 2014, with seven
      older widowers, 71-89 years of age, in North Staffordshire, UK. Interviews
      included personal community diagrams to identify the structure of the older men's
      social relationships. Data analysis comprised thematic analysis of interview
      transcripts and content analysis of personal community diagrams. Three
      overarching themes were identified from the interview data: "Personal identity
      and resilience assist transition," "Continuity in personal communities provides
      stability" and "Changes in social relationships and practices facilitate
      adaptation." The study identified three types of personal community among the
      older widowers, comprising different combinations of family, friends and others.
      The findings illustrate that some older widowers have very restricted personal
      communities which puts them at greater risk of loneliness and social isolation.
      The social needs of long-term carers should be addressed as isolation and
      loneliness can begin long before the death of a spouse. It is important to
      consider gender differences and preferences when designing interventions for
      older people in order to promote engagement, social inclusion and well-being.

PMID- 29349873
TI  - Carbon Molecular Sieve Membranes Derived from Troger's Base-Based Microporous
      Polyimide for Gas Separation.
AB  - Carbon molecular sieve (CMS)-based membranes have attracted great attention
      because of their outstanding gas-separation performance. The polymer precursor is
      a key point for the preparation of high-performance CMS membranes. In this work,
      a microporous polyimide precursor containing a Troger's base unit was used for
      the first time to prepare CMS membranes. By optimizing the pyrolysis procedure
      and the soaking temperature, three TB-CMS membranes were obtained. Gas-permeation
      tests revealed that the comprehensive gas-separation performance of the TB-CMS
      membranes was greatly enhanced relative to that of most state-of-the-art CMS
      membranes derived from polyimides reported so far.

PMID- 29349874
TI  - Assessment by Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass
      Spectrometry of the Effects of Preanalytical Variables on Serum Peptidome
      Profiles Following Long-Term Sample Storage.
AB  - PURPOSE: Human serum and plasma are often used as clinical specimens in
      proteomics analyses, and peptidome profiling of human serum is a promising tool
      for identifying novel disease-associated biomarkers. Matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is widely
      used for peptidomic biomarker discovery. Careful sample collection and handling
      are required as either can have a profound impact on serum peptidome patterns,
      yet the effects of preanalytical variables on serum peptidome profiles have not
      been completely elucidated. The present study investigated the effects of
      preanalytical variables, including storage temperature, duration (up to 12
      months), and thawing methods, on MALDI-TOF MS-based serum peptidome patterns.
      EXPERIMENTAL DESIGN: Aliquots of serum samples were pretreated with weak cation
      exchanger magnetic beads using an automated ClinProtRobot system and then
      analyzed by MALDI-TOF MS. RESULTS: A number of significant differences in peak
      intensities were observed depending on sample processing variables. CONCLUSIONS
      AND CLINICAL RELEVANCE: These peaks can be used as sample quality markers to
      assess the effects of long-term storage on serum peptidome profiles using MALDI
      TOF MS.

PMID- 29349875
TI  - Preclinical QSP Modeling in the Pharmaceutical Industry: An IQ Consortium Survey
      Examining the Current Landscape.
AB  - A cross-industry survey was conducted to assess the landscape of preclinical
      quantitative systems pharmacology (QSP) modeling within pharmaceutical companies.
      This article presents the survey results, which provide insights on the current
      state of preclinical QSP modeling in addition to future opportunities. Our
      results call attention to the need for an aligned definition and consistent
      terminology around QSP, yet highlight the broad applicability and benefits
      preclinical QSP modeling is currently delivering.

PMID- 29349876
TI  - Effectiveness of A Body Shape Index (ABSI) in predicting chronic diseases and
      mortality: a systematic review and meta-analysis.
AB  - Anthropometric measures are simple, inexpensive, noninvasive tools to assess the
      risk of morbidity and mortality. This systematic review assessed the performance
      of A Body Shape Index (ABSI) in predicting hypertension, cardiovascular disease,
      type 2 diabetes and all-cause mortality and compared the differential
      predictability between ABSI and two other common anthropometric measures - body
      mass index and waist circumference. A keyword and reference search were conducted
      in the PubMed and Web of Science for articles published until 1 November 2017.
      Thirty-eight studies were included in the review, including 24 retrospective
      cohort studies and 14 cross-sectional studies conducted in 15 countries. Meta
      analysis found that a standard deviation increase in ABSI was associated with an
      increase in the odds of hypertension by 13% and type 2 diabetes by 35% and an
      increase in cardiovascular disease risk by 21% and all-cause mortality risk by
      55%. ABSI outperformed body mass index and waist circumference in predicting all
      cause mortality but underperformed in predicting chronic diseases. ABSI is highly
      clustered around the mean with a rather small variance, making it difficult to
      define a clinical cutoff for clinical practice. Future studies are warranted to
      assess ABSI's potential usefulness as an anthropometric measure in population
      level health surveillance.

PMID- 29349877
TI  - Engineered and Laser-Processed Chitosan Biopolymers for Sustainable and
      Biodegradable Triboelectric Power Generation.
AB  - Recent advances achieved in triboelectric nanogenerators (TENG) focus on boosting
      power generation and conversion efficiency. Nevertheless, obstacles concerning
      economical and biocompatible utilization of TENGs continue to prevail. Being an
      abundant natural biopolymer from marine crustacean shells, chitosan enables
      exciting opportunities for low-cost, biodegradable TENG applications in related
      fields. Here, the development of biodegradable and flexible TENGs based on
      chitosan is presented for the first time. The physical and chemical properties of
      the chitosan nanocomposites are systematically studied and engineered for
      optimized triboelectric power generation, transforming the otherwise wasted
      natural materials into functional energy devices. The feasibility of laser
      processing of constituent materials is further explored for the first time for
      engineering the TENG performance. The laser treatment of biopolymer films offers
      a potentially promising scheme for surface engineering in polymer-based TENGs.
      The chitosan-based TENGs present efficient energy conversion performance and
      tunable biodegradation rate. Such a new class of TENGs derived from natural
      biomaterials may pave the way toward the economically viable and ecologically
      friendly production of flexible TENGs for self-powered nanosystems in biomedical
      and environmental applications.

PMID- 29349878
TI  - Efficacy of grape seed extract gel in the treatment of chronic periodontitis: A
      randomized clinical study.
AB  - AIM: The aim of the present study was to assess the effectiveness of applying
      grape seed extract (GSE) gel in periodontal pockets for the treatment of chronic
      periodontitis. METHODS: Eighty-six sites with pocket depth (PD) >4 mm were
      selected from five systemically-healthy patients in whom scaling, and root
      planing were performed, and oral instructions were given, a week earlier. PD,
      gingival index (GI), plaque index (PI), and bleeding on probing (BOP) were
      measured, and sites were then divided into the control group (N = 38) and GSE
      group (N = 48). Four doses of formulated 2% mucoadhesive GSE gel were applied to
      GSE group sites at baseline visit (T0), and 3, 6, and 9 days after T0. Similarly,
      a control gel was applied to the control sites. PD, PI, GI and BOP were re
      evaluated after 4 weeks and 6 months of first gel application. RESULTS: Paired t
      test for both the control and GSE groups showed a significant reduction for all
      variables after 6 months of gel application (P < .05). The independent t test
      showed a significant difference (P < .05) only in the reduction of gingival index
      (mean: 0.85 +/- 0.77 for control and 1.3 +/- 0.8 for GSE) and plaque index (mean:
      0.75 +/- 0.71 for control and 1.12 +/- 0.7 for GSE). CONCLUSION: The subgingival
      application of the formulated 2% mucoadhesive GSE gel showed significant
      improvement in the PI and GI only.

PMID- 29349879
TI  - A novel PKLR gene mutation identified using advanced molecular techniques.
AB  - This study's purposes were to diagnose intractable hemolytic anemia and to
      provide guiding treatment for the affected family members. We performed NGS in a
      panel of 600 genes for blood diseases on a patient with obscure hemolytic anemia
      and her parents. We confirmed the diagnosis of pyruvate kinase deficiency,
      identified a novel homozygous mutation of the PKLR gene (NM_000298: exon 6:
      c.T941C: p.I314T), and ruled out other blood diseases in the Chinese family.
      Furthermore, amniotic fluid was taken from the mother during the second
      trimester, and DNA was extracted to analyze the type of PKLR gene mutation. The
      proband received cord blood and bone marrow from the second child of the mother
      for hematopoietic stem cell transplantation and achieved normal hematopoiesis.
      The genetic characterization analysis and genotype-phenotype correlation study of
      PKLR gene suggested that NGS was an effective method to confirm the molecular
      diagnosis of intractable hemolytic anemia. The identification of the mutation
      aided in prenatal diagnosis in the second pregnancy and the effective clinical
      management of the affected family.

PMID- 29349880
TI  - Beyond the realist turn: a socio-material analysis of heart failure self-care.
AB  - For patients living with chronic illnesses, self-care has been linked with
      positive outcomes such as decreased hospitalisation, longer lifespan, and
      improved quality of life. However, despite calls for more and better self-care
      interventions, behaviour change trials have repeatedly fallen short on
      demonstrating effectiveness. The literature on heart failure (HF) stands as a
      case in point, and a growing body of HF studies advocate realist approaches to
      self-care research and policymaking. We label this trend the 'realist turn' in HF
      self-care. Realist evaluation and realist interventions emphasise that the
      relationship between self-care interventions and positive health outcomes is not
      fixed, but contingent on social context. This paper argues socio-materiality
      offers a productive framework to expand on the idea of social context in realist
      accounts of HF self-care. This study draws on 10 interviews as well as researcher
      reflections from a larger study exploring health care teams for patients with
      advanced HF. Leveraging insights from actor-network theory (ANT), this study
      provides two rich narratives about the contextual factors that influence HF self
      care. These descriptions portray not self-care contexts but self-care
      assemblages, which we discuss in light of socio-materiality.

PMID- 29349881
TI  - Speech and language therapists' perspectives of therapeutic alliance construction
      and maintenance in aphasia rehabilitation post-stroke.
AB  - BACKGROUND: Therapeutic alliance refers to the interactional and relational
      processes operating during therapeutic interventions. It has been shown to be a
      strong determinant of treatment efficacy in psychotherapy, and evidence is
      emerging from a range of healthcare and medical disciplines to suggest that the
      construct of therapeutic alliance may in fact be a variable component of
      treatment outcome, engagement and satisfaction. Although this construct appears
      to be highly relevant to aphasia rehabilitation, no research to date has
      attempted to explore this phenomenon and thus consider its potential utility as a
      mechanism for change. AIMS: To explore speech and language therapists'
      perceptions and experiences of developing and maintaining therapeutic alliances
      in aphasia rehabilitation post-stroke. METHODS & PROCEDURES: Twenty-two, in
      depth, semi-structured interviews were conducted with speech and language
      therapists working with people with aphasia post-stroke. Qualitative data were
      analysed using inductive thematic analysis. OUTCOMES & RESULTS: Analysis resulted
      in the emergence of three overarching themes: laying the groundwork; augmenting
      cohesion; and contextual shapers. Recognizing personhood, developing shared
      expectations of therapy and establishing therapeutic ownership were central to
      laying the groundwork for therapeutic delivery. Augmenting cohesion was perceived
      to be dependent on the therapists' responsiveness and ability to resolve both
      conflict and resistance, as part of an ongoing active process. These processes
      were further moulded by contextual shapers such as the patient's family,
      relational continuity and organizational drivers. CONCLUSIONS & IMPLICATIONS: The
      findings suggest that therapists used multiple, complex, relational strategies to
      establish and manage alliances with people with aphasia, which were reliant on a
      fluid interplay of verbal and non-verbal skills. The data highlight the need for
      further training to support therapists to forge purposive alliances. Training
      should develop: therapeutic reflexivity; inclusivity in goal setting, relational
      strategies; and motivational enhancement techniques. The conceptualization of
      therapeutic alliance, however, is only provisional. Further research is essential
      to elucidate the experiences and perceptions of alliance development for people
      with aphasia undergoing rehabilitation.

PMID- 29349882
TI  - Short communication: Persistent socio-economic inequality in frequent headache
      among Danish adolescents from 1991 to 2014.
AB  - BACKGROUND: The association between socio-economic status (SES) and headache
      among adolescents is an understudied issue, and no study has examined whether
      such an association changes over time. The aim was to examine trends in socio
      economic inequality in frequent headache among 11- to 15-year-olds in Denmark
      from 1991 to 2014, using occupational social class (OSC) as indicator of SES.
      METHODS: The study applies data from the Danish part of the international Health
      Behaviour in School-aged Children (HBSC) study. HBSC includes nationally
      representative samples of 11-, 13- and 15-year-olds. This study combines data
      from seven data survey years from 1991 to 2014, participation rate 88.6%, n =
      31,102. We report absolute inequality as per cent difference in frequent headache
      between high and low OSC and relative inequality as odds ratio for frequent
      headache by OSC. RESULTS: In the entire study population, 10.4% reported frequent
      headache. There was a significant increase in frequent headache from 8.0% in 1991
      to 12.9% in 2014, test for trend, p < 0.0001. This increasing trend was
      significant in all OSCs. The prevalence of frequent headache was significantly
      higher in low than high OSC, OR = 1.50 (95% CI: 1.34-1.67). This socio-economic
      inequality in frequent headache was persistent from 1991 to 2014. CONCLUSION:
      There was a significant and persistent socio-economic inequality, i.e. increasing
      prevalence of frequent headache with decreasing OSC. The association between
      socio-economic position and headache did not significantly change over time, i.e.
      the statistical interaction between OSC and survey year was insignificant.
      SIGNIFICANCE: The prevalence of frequent headache among adolescents increases
      with decreasing SES. This socio-economic inequality has been persistent among
      adolescents in Denmark from 1991 to 2014. Clinicians should be aware of this
      social inequality.

PMID- 29349883
TI  - Cellular cannibalism and lichen planus malignancy: A suggestive hypothesis.

PMID- 29349884
TI  - Report of a human autopsy case in maxillary sinuses augmented using a synthetic
      bone substitute: Micro-computed tomographic and histologic observations.
AB  - OBJECTIVE: This study of a human autopsy case aimed to characterize the
      histologic and micro-computed tomographic results of maxillary sinus augmentation
      using a synthetic bone substitute and simultaneous implant placement at 6 years.
      MATERIAL AND METHODS: This report is based on the whole-body donation of a 62
      year-old male patient who died due to bladder cancer. Implants had been placed in
      conjunction with sinus augmentation using a mixture of biphasic calcium phosphate
      and autogenous bone into both maxillary sinuses 6 years prior to the body
      donation. The maxillary sinus areas containing implants were gently removed from
      the cadaver and scanned using high-resolution micro-computed tomography. Samples
      were sectioned, prepared for undecalcified histologic slides and stained with
      haematoxylin-eosin. RESULTS: The augmented volume was observed up to the apex of
      the implants, which were successfully osseointegrated. Cross-sectional micro
      computed tomographic views revealed that the bone-substitute particles were
      embedded in radiopaque-mineralized tissues showing a trabecular pattern around
      the implants. The histologic analysis revealed mature lamellar bone surrounding
      the remaining bone-substitute particles as well as well-organized bone marrow
      spaces in the augment bone area and around the dental implants. CONCLUSION: This
      human autopsy study histologically confirmed the presence of successful bone
      formation and long-term volume stability after sinus augmentation using biphasic
      calcium phosphate and simultaneous implant placement.

PMID- 29349885
TI  - A Hierarchical Z-Scheme alpha-Fe2 O3 /g-C3 N4 Hybrid for Enhanced Photocatalytic
      CO2 Reduction.
AB  - The challenge in the artificial photosynthesis of fossil resources from CO2 by
      utilizing solar energy is to achieve stable photocatalysts with effective CO2
      adsorption capacity and high charge-separation efficiency. A hierarchical direct
      Z-scheme system consisting of urchin-like hematite and carbon nitride provides an
      enhanced photocatalytic activity of reduction of CO2 to CO, yielding a CO
      evolution rate of 27.2 umol g-1 h-1 without cocatalyst and sacrifice reagent,
      which is >2.2 times higher than that produced by g-C3 N4 alone (10.3 umol g-1 h-1
      ). The enhanced photocatalytic activity of the Z-scheme hybrid material can be
      ascribed to its unique characteristics to accelerate the reduction process,
      including: (i) 3D hierarchical structure of urchin-like hematite and preferable
      basic sites which promotes the CO2 adsorption, and (ii) the unique Z-scheme
      feature efficiently promotes the separation of the electron-hole pairs and
      enhances the reducibility of electrons in the conduction band of the g-C3 N4 .
      The origin of such an obvious advantage of the hierarchical Z-scheme is not only
      explained based on the experimental data but also investigated by modeling CO2
      adsorption and CO adsorption on the three different atomic-scale surfaces via
      density functional theory calculation. The study creates new opportunities for
      hierarchical hematite and other metal-oxide-based Z-scheme system for solar fuel
      generation.

PMID- 29349886
TI  - Adaptation of Salmonella enterica to bile: essential role of AcrAB-mediated
      efflux.
AB  - Adaptation to bile is the ability to endure the lethal effects of bile salts
      after growth on sublethal concentrations. Surveys of adaptation to bile in
      Salmonella enterica ser. Tyhimurium reveal that active efflux is essential for
      adaptation while other bacterial functions involved in bile resistance are not.
      Among S. enterica mutants lacking one or more efflux systems, only strains
      lacking AcrAB are unable to adapt, thus revealing an essential role for AcrAB.
      Transcription of the acrAB operon is upregulated in the presence of a sublethal
      concentration of sodium deoxycholate (DOC) while other efflux loci are either
      weakly upregulated or irresponsive. Upregulation of acrAB transcription is strong
      during exponential growth, and weak in stationary cultures. Single cell analysis
      of ethidium bromide accumulation indicates that DOC-induced AcrAB-mediated efflux
      occurs in both exponential and stationary cultures. Upregulation of acrAB
      expression may thus be crucial at early stages of adaptation, while sustained
      AcrAB activity may be sufficient to confer bile resistance in nondividing cells.

PMID- 29349887
TI  - Realizing zT of 2.3 in Ge1-x-y Sbx Iny Te via Reducing the Phase-Transition
      Temperature and Introducing Resonant Energy Doping.
AB  - GeTe with rhombohedral-to-cubic phase transition is a promising lead-free
      thermoelectric candidate. Herein, theoretical studies reveal that cubic GeTe has
      superior thermoelectric behavior, which is linked to (1) the two valence bands to
      enhance the electronic transport coefficients and (2) stronger enharmonic phonon
      phonon interactions to ensure a lower intrinsic thermal conductivity.
      Experimentally, based on Ge1-x Sbx Te with optimized carrier concentration, a
      record-high figure-of-merit of 2.3 is achieved via further doping with In, which
      induces the distortion of the density of states near the Fermi level. Moreover,
      Sb and In codoping reduces the phase-transition temperature to extend the better
      thermoelectric behavior of cubic GeTe to low temperature. Additionally,
      electronic microscopy characterization demonstrates grain boundaries, a high
      density of stacking faults, and nanoscale precipitates, which together with the
      inevitable point defects result in a dramatically decreased thermal conductivity.
      The fundamental investigation and experimental demonstration provide an important
      direction for the development of high-performance Pb-free thermoelectric
      materials.

PMID- 29349888
TI  - Distal amyloid beta-protein fragments template amyloid assembly.
AB  - Amyloid formation is associated with devastating diseases such as Alzheimer's,
      Parkinson's and Type-2 diabetes. The large amyloid deposits found in patients
      suffering from these diseases have remained difficult to probe by structural
      means. Recent NMR models also predict heterotypic interactions from distinct
      peptide fragments but limited evidence of heterotypic packed sheets is observed
      in solution. Here we characterize two segments of the protein amyloid beta
      (Abeta) known to form fibrils in Alzheimer's disease patients. We designed two
      variants of Abeta(19-24) and Abeta(27-32), IFAEDV (I6V) and NKGAIF (N6F) to lower
      the aggregation propensity of individual peptides while maintaining the similar
      interactions between the two segments in their native forms. We found that the
      variants do not form significant amyloid fibrils individually but a 1:1 mixture
      forms abundant fibrils. Using ion mobility-mass spectrometry (IM-MS), hetero
      oligomers up to decamers were found in the mixture while the individual peptides
      formed primarily dimers and some tetramers consistent with a strong heterotypic
      interaction between the two segments. We showed by X-ray crystallography that I6V
      formed a Class 7 zipper with a weakly packed pair of beta-sheets and no
      segregated dry interface, while N6F formed a more stable Class 1 zipper. In a
      mixture of equimolar N6F:I6V, I6V forms a more stable zipper than in I6V alone
      while no N6F or hetero-typic zippers are observed. These data are consistent with
      a mechanism where N6F catalyzes assembly of I6V into a stable zipper and perhaps
      into stable, pure I6V fibrils that are observed in AFM measurements.

PMID- 29349890
TI  - Case report: Cytochrome P450 implications for comorbid ADHD and OCD
      pharmacotherapy.
AB  - TOPIC: This case report details the treatment of an early adolescent already
      receiving treatment for attention-deficit hyperactivity disorder who presents
      with recurrent obsessive-compulsive disorder. Potential atomoxetine (Strattera)
      and fluoxetine (Prozac) interactions via Cytochrome P450 (CYP450) pathways are
      examined and alternate therapies are recommended. PURPOSE: Provide a discussion
      of psychopharmacogenomics, especially in the case of combining medications,
      CYP450 enzymes, and clinical implications in the context of the burgeoning field
      of precision medicine. The following questions are addressed: 1) What are the
      recommendations for pharmacogenetics testing? 2) How should pharmacogenetics
      inform medication selection? 3) What impact should CYP450 knowledge have on
      medication dosing? SOURCES: Peer-reviewed journals, U.S. Health and Human
      Services, National Institutes of Health, National Medical Library, and the
      Clinical Pharmacology database. CONCLUSIONS: Genetic testing as a prescriptive
      tool is not indicated for all medications; however, potential drug-drug
      interactions, narrow therapeutic drug index, and side effect toxicity contribute
      to the need for testing. An understanding of CYP450 metabolism and drug
      interaction as well as metabolism phenotypes should inform prescribing and dosing
      psychotropic medications.

PMID- 29349889
TI  - T-cell Immunoglobulin and ITIM Domain Contributes to CD8+ T-cell
      Immunosenescence.
AB  - Aging is associated with immune dysfunction, especially T-cell defects, which
      result in increased susceptibility to various diseases. Previous studies showed
      that T cells from aged mice express multiple inhibitory receptors, providing
      evidence of the relationship between T-cell exhaustion and T-cell senescence. In
      this study, we showed that T-cell immunoglobulin and immunoreceptor tyrosine
      based inhibitory motif (ITIM) domain (TIGIT), a novel co-inhibitory receptor, was
      upregulated in CD8+ T cells of elderly adults. Aged TIGIT+ CD8+ T cells expressed
      high levels of other inhibitory receptors including PD-1 and exhibited features
      of exhaustion such as downregulation of the key costimulatory receptor CD28,
      representative intrinsic transcriptional regulation, low production of cytokines,
      and high susceptibility to apoptosis. Importantly, their functional defects
      associated with aging were reversed by TIGIT knockdown. CD226 downregulation on
      aged TIGIT+ CD8+ T cells is likely involved in TIGIT-mediated negative immune
      suppression. Collectively, our findings indicated that TIGIT acts as a critical
      immune regulator during aging, providing a strong rationale for targeting TIGIT
      to improve dysfunction related to immune system aging.

PMID- 29349891
TI  - Research on the preparation, uniformity and stability of mixed standard substance
      for rapid detection of goat milk composition.
AB  - Taking fresh goat milk as raw material after filtering, centrifuging, hollow
      fiber ultrafiltration, allocating formula, value detection and preparation
      processing, a set of 10 goat milk mixed standard substances was prepared on the
      basis of one-factor-at-a-time using a uniform design method, and its accuracy,
      uniformity and stability were evaluated by paired t-test and F-test of one-way
      analysis of variance. The results showed that three milk composition contents of
      these standard products were independent of each other, and the preparation using
      the quasi-level design method, and without emulsifier was the best program.
      Compared with detection value by cow milk standards for calibration fast
      analyzer, the calibration by goat milk mixed standard was more applicable to
      rapid detection of goat milk composition, detection value was more accurate and
      the deviation showed less error. Single factor analysis of variance showed that
      the uniformity and stability of the mixed standard substance were better; it
      could be stored for 15 days at 4 degrees C. The uniformity and stability of the
      in-units and inter-units could meet the requirements of the preparation of
      national standard products.

PMID- 29349892
TI  - 'Can the patient speak?': postcolonialism and patient involvement in
      undergraduate and postgraduate medical education.
AB  - CONTEXT: Patients are increasingly being engaged in providing feedback and
      consultation to health care institutions, and in the training of health care
      professionals. Such involvement has the potential to disrupt traditional doctor
      patient power dynamics in significant ways that have not been theorised in the
      medical literature. Critical theories can help us understand how power flows when
      patients are engaged in the training of medical students. METHODS: This paper
      applies postcolonial theory to the involvement of patients in the development and
      delivery of medical education. First, I review and summarise the literature
      around patient involvement in medical education. Subsequently, I highlight how
      postcolonial frameworks have been applied to medical education more broadly,
      extrapolating from the literature to apply a postcolonial lens to the area of
      patient engagement in medical education. CONCLUSION: Concepts from postcolonial
      theory can help medical educators think differently about how patients can be
      engaged in the medical education project in ways that are meaningful and non
      tokenistic. Specifically, the positioning of the patient as 'subaltern' can
      provide channels of resistance against traditional power asymmetries. This has
      curricular and methodological implications for medical education research in the
      area of patient engagement.

PMID- 29349893
TI  - Is overweight/obesity a risk factor for periodontitis in young adults and
      adolescents?: a systematic review.
AB  - BACKGROUND: Obesity in young adults and adolescents is associated with chronic co
      morbidities. This project investigated whether being overweight or obese is a
      risk factor for periodontitis in adolescents (13-17 years) and young adults (18
      34 years). METHODS: A search of 12 databases was conducted using Medical Subject
      Headings/Index and Emtree terms. Based on the Preferred Reporting Items for
      Systematic Reviews and Meta-Analyses, articles published between 2003 and 2016
      were screened that reported periodontal and anthropometric measures. The
      Newcastle-Ottawa Scale was used to appraise the quality of studies. RESULTS: Of
      25 eligible studies from 12 countries, 17 showed an association between obesity
      and periodontitis (odds ratios ranged from 1.1 to 4.5). The obesity indicators of
      body mass index, waist circumference, waist-hip ratio and body fat percentage
      were significantly associated with measures of periodontitis of bleeding on
      probing, plaque index, probing depths, clinical attachment loss, calculus, oral
      hygiene index and community periodontal index. Two prospective cohort studies in
      the review showed no significant association between obesity and periodontitis,
      but these studies had limitations of study design and used inappropriate
      epidemiological diagnostic measures of periodontitis. CONCLUSION: There was
      evidence to suggest that obesity is associated with periodontitis in adolescents
      and young adults. Systematic Review Registration: PROSPERO Registration Number:
      CRD42016046507.

PMID- 29349894
TI  - Assessment of the potential of temporin peptides from the frog Rana temporaria
      (Ranidae) as anti-diabetic agents.
AB  - Temporin A (FLPLIGRVLSGIL-NH2 ), temporin F (FLPLIGKVLSGIL-NH2 ), and temporin G
      (FFPVIGRILNGIL-NH2 ), first identified in skin secretions of the frog Rana
      temporaria, produced concentration-dependent stimulation of insulin release from
      BRIN-BD11 rat clonal beta-cells at concentrations >=1 nM, without cytotoxicity at
      concentrations up to 3 MUM. Temporin A was the most effective. The mechanism of
      insulinotropic action did not involve an increase in intracellular Ca2+
      concentrations. Temporins B, C, E, H, and K were either inactive or only weakly
      active. Temporins A, F, and G also produced a concentration-dependent stimulation
      of insulin release from 1.1B4 human-derived pancreatic beta-cells, with temporin
      G being the most potent and effective, and from isolated mouse islets. The data
      indicate that cationicity, hydrophobicity, and the angle subtended by the charged
      residues in the temporin molecule are important determinants for in vitro
      insulinotropic activity. Temporin A and F (1 MUM), but not temporin G, protected
      BRIN-BD11 cells against cytokine-induced apoptosis (P < 0.001) and augmented (P <
      0.001) proliferation of the cells to a similar extent as glucagon-like peptide-1.
      Intraperitoneal injection of temporin G (75 nmol/kg body weight) together with a
      glucose load (18 mmol/kg body weight) in C57BL6 mice improved glucose tolerance
      with a concomitant increase in insulin secretion whereas temporin A and F
      administration was without significant effect on plasma glucose levels. The study
      suggests that combination therapy involving agents developed from the temporin A
      and G sequences may find application in Type 2 diabetes treatment.

PMID- 29349895
TI  - Men's views and experiences of infant feeding: A qualitative systematic review.
AB  - Although the advantages of breastfeeding are well documented, rates for
      breastfeeding often fall short of international and national targets. Increasing
      attention has been paid to the role of men in infant feeding, but a lot of the
      research about men has been elicited from women, rather than from men themselves.
      To explore these issues further, a systematic review of the qualitative research
      on infant feeding was carried out, focusing specifically on men's own views and
      experiences. Evidence was identified by searching electronic databases (CINAL,
      Cochrane, PubMed, and Scopus), manually searching citations, and by searching the
      grey literature. Studies were included in the review if they discussed men's
      views and experiences of infant feeding and if they reported primary qualitative
      data. Twenty research papers were included in the review, and each study was
      summarised and then analysed thematically to produce a synthesis. Five major
      analytical themes were identified: men's knowledge of infant feeding; men's
      perceptions of their role in infant feeding; positive views on breastfeeding;
      negative views on breastfeeding; and men's experiences of health promotion and
      support. The review concludes by highlighting that although men can play an
      important role in supporting women, they do not have a significant role in infant
      feeding decisions.

PMID- 29349896
TI  - Treatment with low doses of aspirin during chronic phase of experimental Chagas'
      disease increases oesophageal nitrergic neuronal subpopulation in mice.
AB  - Patients with Chagas' disease may develop dysfunctions of oesophageal and colonic
      motility resulting from the degeneration or loss of the myenteric neurons of the
      enteric nervous system. Studies have shown that the use of aspirin, also known as
      acetylsalicylic acid (ASA), influences the pathogenesis of the disease. However,
      this remains controversial. The aim of this study was to evaluate the
      consequences of treatment with low doses of aspirin during the chronic phase of
      Chagas' disease on oesophageal function. Twenty male Swiss mice, 60 days of age,
      were used. The animals were infected with Y strain of Trypanosoma cruzi, injected
      intraperitoneally. Aspirin was given at a dose of 50 mg/kg to some of the
      infected animals, from the 55th to 63rd day after inoculation on consecutive
      days, and from the 65th to 75th day on alternate days. We investigated food
      passage of time, wall structure and nitrergic neuronal population of the distal
      oesophagus. Our data revealed that the use of low doses of aspirin in chronic
      Chagas' disease caused an increase in the number of nitrergic neurons and
      partially prevented hypertrophy of the oesophagus. In addition, the aspirin
      administration impeded Chagas' diseases associated changes in intestinal transit
      time. Thus treatment with aspirin in the chronic phase of Chagas' disease changes
      the natural history of the disease and raises the possibility of using it as a
      new therapeutic approach to the treatment of this aspect of Chagas' disease
      pathology.

PMID- 29349897
TI  - Antibiogram and genetic diversity of Salmonella enterica with zoonotic potential
      isolated from morbid native chickens and pigeons in Egypt.
AB  - AIMS: This study investigated the possible role of Fayoumi chickens and pigeons
      in the transmission of multidrug resistant (MDR) Salmonella with zoonotic
      potential. METHODS AND RESULTS: Morbid Fayoumi chickens (70) and pigeons (30)
      were examined to detect the prevalence and antibiotic resistance of Salmonella
      and to detect and sequence sodC-1 gene as a zoonotic and phylogenetic marker.
      Salmonella isolates were detected in 14.3 and 20% of the examined Fayoumi
      chickens and pigeons, respectively. Salomonella subspecies salamae (43.8%) and S.
      subspecies enterica serovar Bukuru (31.3%) were the most prevalent isolates. All
      tested Salmonella isolates were MDR to at least five classes of antibiotics. S.
      salamae and S. Bukuru isolates that carried blaTEM , qnrS, aadA2 and floR genes
      expressed phenotypic resistance to cefotaxime, ciprofloxacin, streptomycin and
      chloramphenicol, respectively. The aacC gene was detected in one of each S.
      salamae and S. Bukuru isolate, although only the S. Bukuru isolate showed
      phenotypic resistance to gentamicin. The sequence analysis of the sodC-1 gene
      from Salmonella isolates showed clear inter- and intra-subspecies phylogenetic
      segregation. CONCLUSIONS: Fayoumi chickens and pigeons could act as reservoirs of
      MDR Salmonella. SIGNIFICANCE AND IMPACT OF THE STUDY: This study highlights the
      possible emergence of Salmonella subspecies salamae with zoonotic potential.

PMID- 29349899
TI  - Collaborative child home injury prevention in Thailand: An action research study.
AB  - Child home accidental injury is a global health issue, and promoting child safety
      is a pediatric nursing challenge worldwide. Planning child home accidental injury
      prevention requires understanding of factors influencing parents' behavior.
      Evidence suggests that participatory health promotion positively influences
      behavior; however, research on Thai parents is limited. This qualitative, action
      research study aimed to understand Thai parents' experiences of participating in
      a collaborative child home accidental injury prevention program and its influence
      on their behavior. Eight parental mother/father couples from one Thai province
      consented to participate, providing a wide range of data via in-depth individual
      interviews and self-assessment questionnaires. Thematic analysis of interview
      transcripts yielded three themes: collaborative learning, parental behavior
      change, and reflective learning extends beyond families. Participants reported
      that workshop participation improved their child home accidental injury
      prevention behavior. The present study can inform pediatric nursing, child health
      care practice, and child health policy in Thailand and beyond.

PMID- 29349898
TI  - Helenalin Analogues Targeting NF-kappaB p65: Thiol Reactivity and Cellular
      Potency Studies of Varied Electrophiles.
AB  - Helenalin is a pseudoguaianolide natural product that targets Cys38 within the
      DNA binding domain of NF-kappaB transcription factor p65 (RelA). Helenalin
      contains two Michael acceptors that covalently modify cysteines: a alpha
      methylene-gamma-butyrolactone and a cyclopentenone. We recently reported two
      simplified helenalin analogues that mimic the biological activity of helenalin
      and contain both electrophilic moieties. To determine the individual
      contributions of the Michael acceptors toward NF-kappaB inhibition, we
      synthesized a small library of helenalin-based analogues containing various
      combinations of alpha-methylene-gamma-butyrolactones and cyclopentenones. The
      kinetics of thiol addition to a subset of the analogues was measured to determine
      the relative thiol reactivities of the embedded electrophiles. Additionally, the
      cellular NF-kappaB inhibitory activities of the analogues were determined to
      elucidate the contributions of each Michael acceptor to biological potency. Our
      studies suggest the alpha-methylene-gamma-butyrolactone contributes most
      significantly to the NF-kappaB inhibition of our simplified helenalin analogues.

PMID- 29349900
TI  - Primary cardiac angiosarcoma: A case report.
AB  - Cardiac angiosarcomas are the most common primary malignant cardiac tumors in
      adults. The diagnosis is often delayed due to nonspecific clinical symptoms at
      presentation. The cornerstones of diagnosis are echocardiography and the
      histological evaluation of the cardiac biopsy. The knowledge on the treatment is
      limited; the outcomes of chemotherapy, radiotherapy, complete surgical removal,
      and heart transplantation are controversial. We report a 38-year-old woman with a
      primary heart tumor which infiltrated the right atrial wall and the pericardium
      and caused pericardial effusion. Angiosarcoma was verified histologically. The
      surgical excision could not be radical, and the patient died 3 months from
      diagnosis.

PMID- 29349901
TI  - Inflammatory back pain and associated disease conditions among patients with
      chronic low back pain in Bangladesh.
AB  - AIM: Inflammatory back pain (IBP) is the earliest symptom of axial and other
      forms of spondyloarthritis (SpA). However, there are no published data on
      prevalence of IBP among patients suffering from chronic low back pain (CLBP) in
      Bangladesh. In this study, we estimated the prevalence of IBP and the subtypes of
      SpA in a tertiary hospital in Bangladesh. METHODS: This 1 year cross-sectional
      study was conducted among 240 CLBP patients in a rheumatology outpatient clinic.
      Assessment of Spondyloarthritis International Society classification criteria of
      IBP and predefined recognized classification criteria were followed to define
      different subtypes of SpA. Means and standard deviations were reported for
      continuous variables. Descriptive and bi-variate analyses were accordingly
      performed. RESULTS: Of 240 CLBP patients, 60 (25%) had IBP and 180 (75%) had
      mechanical back pain (MBP). Among the 60 IBP patients, 52 (86.6%) had
      predominantly axial SpA (axSpA) and eight (13.4%) had predominantly peripheral
      spondyloarthritis. In the axSpA group, 49 (94.2%) had radiographic axSpA (rd
      axSpA) also known as AS and three (5.8%) had non-radiographic axSpA (nr-axspA).
      AxSpA patients could be divided into eight (15.35%) with psoriasis, two (3.8%)
      with reactive arthritis and one patient (1.9%) had arthritis associated with
      inflammatory bowel disease. Fifty (83.3%) IBP and 73 (40.6%) MBP patients had age
      at onset of back pain < 40 years. Forty-two (70%) of the IBP and 100 (55.6%) of
      the MBP patients had normal body mass index. All these differences were
      statistically significant (P <= 0.0001). CONCLUSIONS: Inflammatory back pain is
      common among patients presenting with CLBP. The commonest cause of IBP is AS,
      followed by PsA and nr-axSpA.

PMID- 29349902
TI  - Association between pre-sarcopenia, sarcopenia, and bone mineral density in
      patients with chronic hepatitis C.
AB  - BACKGROUND: Preserved skeletal muscle is essential for the maintenance of healthy
      bone. Loss of bone mineral density (BMD) and muscle strength, considered a
      predictor of BMD, have been demonstrated in patients with cirrhosis, but they are
      poorly studied in chronic hepatitis C (CHC) without cirrhosis. Thus, we aimed to
      evaluate the prevalence of low BMD and its association with body composition,
      muscle strength, and nutritional status in CHC. METHODS: One hundred and four
      subjects [mean age, 50.5 +/- 11.3 years; 75.0% males; 67.3% non-cirrhotic; and
      32.7% with compensated cirrhosis] with CHC, prospectively, underwent scanning of
      the lean tissue, appendicular skeletal muscle mass (ASM), fat mass, lumbar spine,
      hip, femoral neck, and whole-body BMD by dual-energy X-ray absorptiometry. Muscle
      strength was assessed by dynamometry. Sarcopenia was defined by the presence of
      both low, ASM/height2 (ASMI) and low muscle strength according to the European
      Working Group on Sarcopenia in Older People criteria. The cut-off points for low
      ASMI and low muscle strength, for women and men, were < 5.45 and < 7.26 kg/m2 and
      < 20 and < 30 kg, respectively. According to the adopted World Health
      Organization criteria in men aged > 50 years, the T-score of osteopenia is
      between -1.0 and -2.49 standard deviation (SD) below the young average value and
      of osteoporosis is >=-2.5 SD below the young normal mean for men, and the Z-score
      of low bone mass is <=-2.0 SD below the expected range in men aged < 50 years and
      women in the menacme. Nutritional status evaluation was based on the Controlling
      Nutritional Status score. RESULTS: Low BMD, low muscle strength, pre-sarcopenia,
      sarcopenia, and sarcopenic obesity were observed in 34.6% (36/104), 27.9%
      (29/104), 14.4% (15/104), 8.7% (9/104), and 3.8% (4/104) of the patients,
      respectively. ASMI was an independent predictor of BMD (P < 0.001). Sarcopenia
      was independently associated with bone mineral content (P = 0.02) and
      malnutrition (P = 0.01). In 88.9% of the sarcopenic patients and in all with
      sarcopenic obesity, BMI was normal. The mid-arm muscle circumference was
      positively correlated with ASMI (r = 0.88; P < 0.001). CONCLUSIONS: This is the
      first study to demonstrate that ASM is an independent predictor of BMD in CHC.
      Mid-arm muscle circumference coupled with handgrip strength testing should be
      incorporated into routine clinical practice to detect low muscle mass, which may
      be underdiagnosed when only BMI is used. These findings may influence clinical
      decision-making and contribute to the development of effective strategies to
      screen the musculoskeletal abnormalities in CHC patients, independently of the
      stage of the liver disease.

PMID- 29349904
TI  - Lysosome remodelling and adaptation during phagocyte activation.
AB  - Lysosomes are acidic and hydrolytic organelles responsible for receiving and
      digesting cargo acquired during endocytosis, phagocytosis, and autophagy. For
      macrophages and dendritic cells, the lysosome is kingpin, playing a direct role
      in microbe killing and antigen processing for presentation. Strikingly, the
      historic view that lysosomes are homogeneous and static organelles is being
      replaced with a more elegant paradigm, in which lysosomes are heterogeneous,
      dynamic, and respond to cellular needs. For example, lysosomes are signalling
      platforms that integrate stress detection and molecular decision hubs such as the
      mTOR complex 1 and AMPK to modulate cellular activity. These signals can even
      adjust lysosome activity by modulating transcription factors such as
      transcription factor EB (TFEB) and TFE3 that govern lysosome gene expression.
      Here, we review lysosome remodelling and adaptation during macrophage and
      dendritic cell stimulation. First, we assess the functional outcomes and
      regulatory mechanisms driving the dramatic restructuring of lysosomes from
      globular organelles into a tubular network during phagocyte activation. Second,
      we discuss lysosome adaptation and scaling in macrophages driven by TFEB and TFE3
      stimulation in response to phagocytosis and microbe challenges. Collectively, we
      are beginning to appreciate that lysosomes are dynamic and adapt to serve
      phagocyte differentiation in response to microbes and immune stress.

PMID- 29349903
TI  - GP73 promotes invasion and metastasis of bladder cancer by regulating the
      epithelial-mesenchymal transition through the TGF-beta1/Smad2 signalling pathway.
AB  - This study investigated the effects of Golgi membrane protein 73 (GP73) on the
      epithelial-mesenchymal transition (EMT) and on bladder cancer cell invasion and
      metastasis through the TGF-beta1/Smad2 signalling pathway. Paired bladder cancer
      and adjacent tissue samples (102) and normal bladder tissue samples (106) were
      obtained. Bladder cancer cell lines (T24, 5637, RT4, 253J and J82) were selected
      and assigned to blank, negative control (NC), TGF-beta, thrombospondin-1 (TSP-1),
      TGF-beta1+ TSP-1, GP73-siRNA-1, GP73-siRNA-2, GP73-siRNA-1+ TSP-1, GP73-siRNA-1+
      pcDNA-GP73, WT1-siRNA and WT1-siRNA + GP73-siRNA-1 groups. Expressions of GP73,
      TGF-beta1, Smad2, p-Smad2, E-cadherin and vimentin were detected using RT-qPCR
      and Western blotting. Cell proliferation, migration and invasion were determined
      using MTT assay, scratch testing and Transwell assay, respectively. Compared with
      the blank and NC groups, levels of GP73, TGF-beta1, Smad2, p-Smad2, N-cadherin
      and vimentin decreased, and levels of WT1 and E-cadherin increased in the GP73
      siRNA-1 and GP73-siRNA-2 groups, while the opposite results were observed in the
      WT1 siRNA, TGF-beta, TSP-1 and TGF-beta + TSP-1 groups. Cell proliferation,
      migration and invasion notably decreased in the GP73-siRNA-1 and GP73-siRNA-2
      groups in comparison with the blank and NC groups, while in the WT1 siRNA, TGF
      beta, TSP-1 and TGF-beta + TSP-1 groups, cell migration, invasion and
      proliferation showed the reduction after the EMT. These results suggest that GP73
      promotes bladder cancer invasion and metastasis by inducing the EMT through down
      regulating WT1 levels and activating the TGF-beta1/Smad2 signalling pathway.

PMID- 29349906
TI  - Pregnancy greatly affects the steroidal module of the Athlete Biological
      Passport.
AB  - Concentrations of urinary steroids are measured in anti-doping test programs to
      detect doping with endogenous steroids. These concentrations are combined into
      ratios and followed over time in the steroidal module of the Athlete Biological
      Passport (ABP). The most important ratio in the ABP is the
      testosterone/epitestosterone (T/E) ratio but this ratio is subject to intra
      individual variations, especially large in women, which complicates
      interpretation. In addition, there are other factors affecting T/E. Pregnancy,
      for example, is known to affect the urinary excretion rate of epitestosterone and
      hence the T/E ratio. However, the extent of this variation and how pregnancy
      affect other ratios has not been fully evaluated. Here we have studied the
      urinary steroid profile, including 19-norandrosterone (19-NA), in 67 pregnant
      women and compared to postpartum. Epitestosterone was higher and, consequently,
      the T/E and 5alphaAdiol/E ratios were lower in the pregnant women.
      Androsterone/etiocholanolone (A/Etio) and 5alphaAdiol/5betaAdiol, on the other
      hand, were higher in the first trimester as compared to postpartum (p<0.0001 and
      p=0.0396, respectively). There was no difference in A/T during pregnancy or
      after. 19-NA was present in 90.5% of the urine samples collected from pregnant
      women. In this study, we have shown that the steroid profile of the ABP is
      affected by pregnancy, and hence can cause atypical passport findings. These
      atypical findings would lead to unnecessary confirmation procedures, if the
      patterns of pregnancy are not recognized by the ABP management units.

PMID- 29349905
TI  - Would you like to add a weight after this blood pressure, doctor? Discovery of
      potentially actionable associations between the provision of multiple screens in
      primary care.
AB  - RATIONALE, AIMS, AND OBJECTIVE: Guidelines recommend screening for risk factors
      associated with chronic diseases but current electronic prompts have limited
      effects. Our objective was to discover and rank associations between the presence
      of screens to plan more efficient prompts in primary care. METHODS: Risk factors
      with the greatest impact on chronic diseases are associated with blood pressure,
      body mass index, waist circumference, glycaemic and lipid levels, smoking,
      alcohol use, diet, and exercise. We looked for associations between the presence
      of screens for these in electronic medical records. We used association rule
      mining to describe relationships among items, factor analysis to find latent
      categories, and Cronbach alpha to quantify consistency within latent categories.
      RESULTS: Data from 92 140 patients in or around Toronto, Ontario, were included.
      We found positive correlations (lift >1) between the presence of all screens. The
      presence of any screen was associated with confidence greater than 80% that other
      data on items with high prevalence (blood pressure, glycaemic and lipid levels,
      or smoking) would also be present. A cluster of rules predicting the presence of
      blood pressure were ranked highest using measures of interestingness such as
      standardized lift. We found 3 latent categories using factor analysis; these were
      laboratory tests, vital signs, and lifestyle factors; Cronbach alpha ranged
      between .58 for lifestyle factors and .88 for laboratory tests. CONCLUSIONS:
      Associations between the provision of important screens can be discovered and
      ranked. Rules with promising combinations of associated screens could be used to
      implement data driven alerts.

PMID- 29349907
TI  - Accelerated Hydrogen Evolution Kinetics on NiFe-Layered Double Hydroxide
      Electrocatalysts by Tailoring Water Dissociation Active Sites.
AB  - Owing to its earth abundance, low kinetic overpotential, and superior stability,
      NiFe-layered double hydroxide (NiFe-LDH) has emerged as a promising
      electrocatalyst for catalyzing water splitting, especially oxygen evolution
      reaction (OER), in alkaline solutions. Unfortunately, as a result of extremely
      sluggish water dissociation kinetics (Volmer step), hydrogen evolution reaction
      (HER) activity of the NiFe-LDH is rather poor in alkaline environment. Here a
      novel strategy is demonstrated for substantially accelerating the hydrogen
      evolution kinetics of the NiFe-LDH by partially substituting Fe atoms with Ru. In
      a 1 m KOH solution, the as-synthesized Ru-doped NiFe-LDH nanosheets (NiFeRu-LDH)
      exhibit excellent HER performance with an overpotential of 29 mV at 10 mA cm-2 ,
      which is much lower than those of noble metal Pt/C and reported electrocatalysts.
      Both experimental and theoretical results reveal that the introduction of Ru
      atoms into NiFe-LDH can efficiently reduce energy barrier of the Volmer step,
      eventually accelerating its HER kinetics. Benefitting from its outstanding HER
      activity and remained excellent OER activity, the NiFeRu-LDH steadily drives an
      alkaline electrolyzer with a current density of 10 mA cm-2 at a cell voltage of
      1.52 V, which is much lower than the values for Pt/C-Ir/C couple and state-of-the
      art overall water-splitting electrocatalysts.

PMID- 29349908
TI  - Robotic-assisted coronary artery bypass surgery: an 18-year single-centre
      experience.
AB  - BACKGROUND: Minimally invasive robot-assisted direct coronary artery bypass
      (RADCAB) has emerged as a feasible minimally invasive surgical technique for
      revascularization that might offer several potential advantages over conventional
      approaches. We present our 18-year experience in RADCAB. METHODS: Between
      February 1998 and February 2016, 605 patients underwent RADCAB. Patients
      underwent post-procedural selective graft patency assessment using cardiac
      catheterization. RESULTS: The mortality rate was 0.3%. The rate of conversion to
      sternotomy for any cause was reduced from 16.0% of the first 200 cases to 6.9% of
      the last 405 patients. The patency rate of the LITA-to-LAD anastomosis was 97.4%.
      Surgical re-exploration for bleeding occurred in 1.8% of patients, and the
      transfusion rate was 9.2%. Average ICU stay was 1.2 +/- 1.4 days, and average
      hospital stay was 4.8 +/- 2.9 days. CONCLUSIONS: Robot-assisted coronary artery
      bypass grafting is safe, feasible and it seems to represent an effective
      alternative to traditional coronary artery bypass grafting in selected patients.

PMID- 29349909
TI  - A literature review and hypothesis for the etiologies of cervical and root
      caries.
AB  - : The presence of endogenous acids from bacteria acting on a suitable substrate
      combined with sources of exogenous biocorrosives such as exogenous acids and
      proteolytic enzymes in areas of stress concentration are hypothesized to lead to
      the development and progression of cervical and root caries (RC). Quantifying the
      effects of each of the mechanisms (stress and biocorrosion) is a daunting task to
      investigate since so many factors are involved at various times in the etiology
      of noncarious cervical lesions (NCCLs), cervical caries (CC), and RC. Frictional
      action of the tongue has a cleansing effect and lingual serous saliva, which has
      a high flow rate buffering capacity from bicarbonates seem to account for the
      paucity of lingual NCCLs, cervical, and RC in these areas of teeth. Future
      studies are indicated to determine the effects of stress and biocorrosion and
      their factors in the etiology of CC and RC. CLINICAL SIGNIFICANCE: This
      manuscript presents hypothetical and literary information that the combined
      effects of stress concentration and biocorrosion contribute to the formation as
      well as progression of cervical and root caries.

PMID- 29349910
TI  - Accuracy of a new elastomeric impression material for complete-arch dental
      implant impressions.
AB  - AIM: The aim of the present study was to assess the accuracy of multi-unit dental
      implant casts obtained from two elastomeric impression materials, vinyl polyether
      silicone (VPES) and polyether (PE), and to test the effect of splinting of
      impression copings on the accuracy of implant casts. METHODS: Forty direct
      impressions of a mandibular reference model fitted with six dental implants and
      multibase abutments were made using VPES and PE, and implant casts were poured (N
      = 20). The VPES and PE groups were split into four subgroups of five each, based
      on splinting type: (a) no splinting; (b) bite registration polyether; (c) bite
      registration addition silicone; and (d) autopolymerizing acrylic resin. The
      accuracy of implant-abutment replica positions was calculated on the experimental
      casts, in terms of interimplant distances in the x, y, and z-axes, using a
      coordinate measuring machine; values were compared with those measured on the
      reference model. Data were analyzed using non-parametrical Kruskal-Wallis and
      Mann-Whitney tests at alpha = .05. RESULTS: The differences between the two
      impression materials, VPES and PE, regardless of splinting type, were not
      statistically significant (P>.05). Non-splinting and splinting groups were also
      not significantly different for both PE and VPES (P>.05). CONCLUSIONS: The
      accuracy of VPES impression material seemed comparable with PE for multi-implant
      abutment-level impressions. Splinting had no effect on the accuracy of implant
      impressions.

PMID- 29349911
TI  - Identification of fish source Vibrio alginolyticus and evaluation of its
      bacterial ghosts vaccine immune effects.
AB  - Vibrio alginolyticus (V. alginolyticus) is a common pathogen for humans and
      marine aquatic animals. Vibriosis of marine aquatic animals, caused by V.
      alginolyticus, has become more prevalent globally in recent years. Hence, a safe
      and effective vaccine is urgently needed for the control of this disease. Here,
      the strain 16-3 isolated from the large yellow croaker (Larimichthys crocea)
      suffered from canker was identified as V. alginolyticus based on morphological,
      biochemical, and 16S rDNA sequencing analysis. Then, recombinant temperature
      controlled lysis plasmid pBV220-lysisE was electroporated into the strain 16-3 to
      generate V. alginolyticus bacterial ghosts (VaBGs) by inducing lysis gene E
      expression, and the safety and immune effects of VaBGs were further investigated
      in mice and large yellow croaker. The results showed that VaBGs were as safe as
      formalin-killed V. alginolyticus cells (FKC) to mice and fish. Compared with FKC
      and PBS groups, significant elevations of the serum agglutinating antibody titer,
      serum bactericidal activity, lymphocyte proliferative responses, and levels of
      four different cytokines (Th1 type: IL-2, TNF-alpha; Th2 type: IL-4 and IL-6) in
      serum were detected in the VaBGs group, indicating that a Th1/Th2-mediated mixed
      immune response was elicited by the VaBGs. More importantly, after challenged
      with the parent strain 16-3, VaBGs-vaccinated mice and fish showed higher
      protection than FKC-vaccinated mice, the relative percent of survival (RPS) being
      60%, 66.7% and 40%, respectively. Taken together, this is the first demonstration
      that the newly constructed V. alginolyticus ghosts may be developed as a safe and
      effective vaccine against V. alginolyticus infection in aquaculture.

PMID- 29349912
TI  - Meta-analysis generates and prioritizes hypotheses for translational microbiome
      research.

PMID- 29349913
TI  - Eukaryotic phytoplankton community spatiotemporal dynamics as identified through
      gene expression within a eutrophic estuary.
AB  - Over the span of a year, we investigated the interactions between biotic and
      abiotic factors within the eutrophic Neuse River Estuary (NRE). Through
      metatranscriptomic sequencing in combination with water quality measurements, we
      show that there are different metabolic strategies deployed along the NRE. In the
      upper estuary, taxonomically resolved phytoplankton groups express more
      transcripts of genes for synthesis of cellular components and carbon metabolism
      whereas in the lower estuary, transcripts allocated to nutrient metabolism and
      transport were more highly expressed. Metabolisms for polysaccharide synthesis
      and transportation were elevated in the lower estuary and could be reflective of
      unbalanced growth and/or interactions with their surrounding microbial consortia.
      Our results indicate phytoplankton have high metabolic activity, suggestive of
      increased growth rates in the upper estuary and display patterns reflective of
      nutrient limitation in the lower estuary. Among all the environmental parameters
      varying along the NRE, nitrogen availability is found to be the main driving
      factor for the observed spatial divergence.

PMID- 29349914
TI  - Dismal science and medicine embrace.

PMID- 29349915
TI  - Surrogacy legislation remains complex and unsatisfactory.

PMID- 29349917
TI  - Risk stratification for febrile neutropenia in patients with testicular germ cell
      tumors.
AB  - The aim of this study was to detect risk factors for febrile neutropenia (FN) in
      patients with testicular germ cell tumors (TGCT). In this retrospective cohort
      study at the Medical University of Graz, we included 413 consecutive TGCT
      patients who received adjuvant or curative treatment with cisplatin-based
      chemotherapy. FN occurred in 70 (16.9%) of 413 patients. In univariable logistic
      regression, higher age (odds ratio (OR) per 5 years = 1.17, 95% CI: 1.02-1.35, P
      = 0.022), reduced performance status (PS) (OR = 2.73, 1.47-5.06, P = 0.001),
      seminomatous histology (OR = 2.19, 1.26-3.78, P = 0.005), poor IGCCCG risk class
      (OR = 4.20, 1.71-10.33, P = 0.002), and prior radiotherapy (pRTX) (OR = 8.98,
      2.09-38.61, P = 0.003) were associated with a higher risk of FN. In multivariable
      analysis adjusting for age and risk classification, only poor PS (OR = 2.06, 1.05
      4.03, P = 0.035), seminomatous histology (OR = 2.08, 1.01-4.26, P = 0.047), and
      pRTX (OR = 7.31, 1.61-33.17, P = 0.010) prevailed. In the subgroup of seminoma
      patients (n = 104), only pRTX predicted for FN risk (OR = 5.60, 1.24-25.34, P =
      0.025). Five of eight seminoma patients with pRTX developed FN (63%), as compared
      to 22 FN cases (23%) in the 96 seminoma patients without pRTX (P = 0.027). The
      eight seminoma patients who received pRTX had significantly lower pre-chemo white
      blood counts (4.7 vs. 6.5 G/L), neutrophil counts (3.2 vs. 4.3 G/L), and platelet
      counts (185 vs. 272 G/L) than patients without pRTX (all P < 0.0001). TGCT
      patients with a reduced performance status or who had been previously treated
      with radiotherapy have an increased risk for neutropenic fever during
      chemotherapy.

PMID- 29349918
TI  - Dual Drug Backboned Shattering Polymeric Theranostic Nanomedicine for Synergistic
      Eradication of Patient-Derived Lung Cancer.
AB  - Most of the current nanoparticle-based therapeutics worldwide failing in clinical
      trials face three major challenges: (i) lack of an optimum drug delivery platform
      with precise composition, (ii) lack of a method of directly monitoring the fate
      of a specific drug rather than using any other labelling molecules as a
      compromise, and (iii) lack of reliable cancer models with high fidelity for drug
      screen and evaluation. Here, starting from a PP2A inhibitor demethylcantharidin
      (DMC) and cisplatin, the design of a dual sensitive dual drug backboned
      shattering polymer (DDBSP) with exact composition at a fixed DMC/Pt ratio for
      precise nanomedicine is shown. DDBSP self-assembled nanoparticle (DD-NP) can be
      triggered intracellularly to break down in a chain-shattering manner to release
      the dual drugs payload. Moreover, DD-NP with extremely high Pt heavy metal
      content in the polymer chain can directly track the drug itself via Pt-based drug
      mediated computer tomography and ICP-MS both in vitro and in vivo. Finally, DD-NP
      is used to eradicate the tumor burden on a high-fidelity patient-derived lung
      cancer model for the first time.

PMID- 29349919
TI  - Analysis of Follow-Up Methods of Vascular Access and Patient Outcomes in
      Hemodialysis at a Tertiary Care Hospital in China.
AB  - Arteriovenous fistula is the preferred option for vascular access in hemodialysis
      patients. The aim of this study was to assess different follow-up methods for
      hemodialysis patients in our hemodialysis center in China. A cohort of 124
      patients with stage 3 chronic kidney disease was recruited and double-blind
      randomly assigned into two groups. Patients in Group A received phone calls to
      schedule their next consultation a week in advance. Patients in Group B scheduled
      their next appointment at the end of each visit. A total of 116 patients were
      included in the study and eight dropped out. Twenty-seven patients (46.4%) in
      Group A and 13 patients (22.4%) in Group B had an AVF prior to hemodialysis (P =
      0.006), and 44.8% of patients in Group A and 15.5% of patients in Group B were
      using AVFs at the initiation of dialysis (P = 0.003). Sixteen patients (27.6%) in
      Group A and 24 patients (41.3%) in Group B required central venous catheters due
      to acute on chronic kidney disease and 13 patients (22.4%) in Group A and 21
      patients (36.2%) in Group B required central venous catheters due to patient
      related delays (P = 0.02). At the end of the study, seven patients in Group A
      died and 17 patients in Group B died (P = 0.027). The patients who received phone
      calls to schedule appointments in advance had a higher rate of arteriovenous
      fistulas prior to dialysis and at hemodialysis initiation had a reduced incidence
      of acute on chronic kidney disease and patient-related delays, and had an
      improved prognosis.

PMID- 29349920
TI  - Hyperuricemia in Asian psoriatic arthritis patients.
AB  - AIM: It is generally accepted that hyperuricemia is commonly associated with
      psoriatic arthritis (PsA). However, variations in ethnicity, diet and habitat may
      contribute to differences in prevalence and risk factors for hyperuricemia in PsA
      patients. Moreover, Asian specific data is deficient. The primary objective of
      the present study was to determine the prevalence of hyperuricemia among PsA
      patients. The secondary objective was to explore its associated risk factors.
      METHODS: This was a multi-center, cross-sectional observational study of 160 PsA
      patients from local Rheumatology clinics. Serum uric acid (SUA) level and other
      clinical parameters were measured and hyperuricemia was defined as SUA level
      greater or equal to 360 umol/L in females and 420 umol/L in males. RESULTS: Forty
      nine of 160 patients (30.6%) had hyperuricemia, of which 32 were men, 17 were
      women. Among those with hyperuricemia, mean SUA level was 500.7 +/- 95.9 umol/L
      and 427.8 +/- 83.1 umol/L in males and females, respectively. Univariate analysis
      found: (i) overweight status; (ii) obesity; (iii) Psoriasis Area and Severity
      Index; (iv) body surface area; (v) severe skin involvement, as being potentially
      associated with hyperuricemia. Regression model identified overweight status
      increased the likelihood of hyperuricemia in PsA, with an odds ratio of 4.4 (95%
      CI: 2.0-9.5). Furthermore, there was moderately positive correlation (r = 0.37)
      between body mass index (BMI) and SUA level. No associations were found between
      arthritis conditions and duration, lipid profile, creatinine clearance; and
      hyperuricemia. CONCLUSION: A significant proportion of PsA patients had
      asymptomatic hyperuricemia. It was closely related with BMI, which represented
      metabolic dysregulation; but not with severity of skin disease, joint involvement
      or renal function.

PMID- 29349921
TI  - Community pharmacists' views on the regulation of complementary medicines and
      complementary-medicines practitioners: a qualitative study in New Zealand.
AB  - OBJECTIVES: To examine community pharmacists' perspectives on CMs regulation in
      New Zealand, where proposals for CMs regulations had recently been suspended and
      where, currently, CMs are only weakly regulated. METHODS: Qualitative, in-depth,
      semi-structured interviews with New Zealand practising community pharmacists are
      identified through purposive and convenience sampling. Data were analysed using a
      general inductive approach. KEY FINDINGS: Participants held mixed views regarding
      harmonisation of CMs regulations across Australia and NZ; some supported an NZ
      national regulatory framework for CMs, based on the Australian system.
      Participants recognised the current CMs regulatory framework in NZ as inadequate,
      that regulation was required to some extent, and that mandatory regulation was
      not necessarily required. A key reason given in support of CMs regulations was
      the need for greater assurances around quality of CMs. Participants also
      supported a regulatory framework that incorporated assessment of the safety of
      CMs, but were less convinced of the need for, or feasibility of, requiring
      evidence of efficacy from clinical trials. Participants believed that regulation
      of CMs practitioners, such as herbalists, and CMs retailers was important,
      although there were mixed views as to whether regulation should be statutory or
      whether self-regulation would be adequate. CONCLUSIONS: On the basis of these
      findings, pharmacists would be expected to welcome proposals for national
      regulations for CMs in NZ: such regulations should address concerns regarding
      product quality, inappropriate health claims and supporting evidence, and
      therefore should support pharmacists in meeting their obligations under the NZ
      Pharmacy Council's Code of Ethics.

PMID- 29349922
TI  - Association between breast milk intake at 9-10 months of age and growth and
      development among Malawian young children.
AB  - World Health Organization recommends exclusive breastfeeding for infants for the
      first 6 months of life, followed by introduction of nutritious complementary
      foods alongside breastfeeding. Breast milk remains a significant source of
      nourishment in the second half of infancy and beyond; however, it is not clear
      whether more breast milk is always better. The present study was designed to
      determine the association between amount of breast milk intake at 9-10 months of
      age and infant growth and development by 12-18 months of age. The study was
      nested in a randomized controlled trial conducted in Malawi. Regression analysis
      was used to determine associations between breast milk intake and growth and
      development. Mean (SD) breast milk intake at 9-10 months of age was 752 (244)
      g/day. Mean (SD) length-for-age z-score at 12 months and change in length-for-age
      z-score between 12 and 18 months were -1.69 (1.0) and -0.17 (0.6), respectively.
      At 18 months, mean (SD) expressive vocabulary score was 32 (24) words and median
      (interquartile range) skills successfully performed for fine, gross, and overall
      motor skills were 21 (19-22), 18 (16-19), and 38 (26-40), respectively. Breast
      milk intake (g/day) was not associated with either growth or development.
      Proportion of total energy intake from breast milk was negatively associated with
      fine motor (beta = -0.18, p = .015) but not other developmental scores in models
      adjusted for potential confounders. Among Malawian infants, neither breast milk
      intake nor percent of total energy intake from breast milk at 9-10 months was
      positively associated with subsequent growth between 12 and 18 months, or
      development at 18 months.

PMID- 29349923
TI  - Magnetic Macroporous Hydrogels as a Novel Approach for Perfused Stem Cell Culture
      in 3D Scaffolds via Contactless Motion Control.
AB  - There is an urgent need for 3D cell culture systems that avoid the
      oversimplifications and artifacts of conventional culture in 2D. However, 3D
      culture within the cavities of porous biomaterials or large 3D structures
      harboring high cell numbers is limited by the needs to nurture cells and to
      remove growth-limiting metabolites. To overcome the diffusion-limited transport
      of such soluble factors in 3D culture, mixing can be improved by pumping,
      stirring or shaking, but this in turn can lead to other problems. Using pumps
      typically requires custom-made accessories that are not compatible with
      conventional cell culture disposables, thus interfering with cell production
      processes. Stirring or shaking allows little control over movement of scaffolds
      in media. To overcome these limitations, magnetic, macroporous hydrogels that can
      be moved or positioned within media in conventional cell culture tubes in a
      contactless manner are presented. The cytocompatibility of the developed
      biomaterial and the applied magnetic fields are verified for human hematopoietic
      stem and progenitor cells (HSPCs). The potential of this technique for perfusing
      3D cultures is demonstrated in a proof-of-principle study that shows that
      controlled contactless movement of cell-laden magnetic hydrogels in culture media
      can mimic the natural influence of differently perfused environments on HSPCs.

PMID- 29349924
TI  - Parental supervision for their children's toothbrushing: Mediating effects of
      planning, self-efficacy, and action control.
AB  - OBJECTIVES: With 60-90% of children worldwide reportedly experiencing dental
      caries, poor oral health in the younger years is a major public health issue. As
      parents are important to children's oral hygiene practices, we examined the key
      self-regulatory behaviours of parents for supervising their children's
      toothbrushing using the health action process approach. DESIGN AND METHOD:
      Participants (N = 281, 197 mothers) comprised Australian parents of 2- to 5-year
      olds. A longitudinal design was used to investigate the sequential mediation
      chain for the effect of intention (Time 1) on parental supervision for their
      youngest child's toothbrushing (Time 3), via self-efficacy and planning (Time 2),
      and action control (Time 3). RESULTS: A latent-variable structural equation
      model, controlling for baseline behaviour and habit, revealed significant
      indirect effects from intention via self-efficacy and action control and
      intention via planning and action control, on parental supervision behaviour. The
      model was a good fit to the data, explaining 74% of the variance in parents'
      supervising behaviour for their children's toothbrushing. CONCLUSION: While
      national recommendations are provided to guide parents in promoting good oral
      hygiene practices with their children, current results show the importance of
      going beyond simple knowledge transmission to support parents' intentions to
      supervise their children's toothbrushing actually materialize. Current findings
      make a significant contribution to the cumulative empirical evidence regarding
      self-regulatory components in health behaviour change and can inform intervention
      development to increase parents' participation in childhood oral hygiene
      practices, thus helping to curb rising oral health conditions and diseases.
      Statement of contribution What is already known on this subject? Self-regulatory
      skills are important to translate intentions into behaviour. Self-efficacy,
      planning, and action control are key self-regulatory skills for behaviour change.
      What does this study add? Self-regulatory skills are needed for parents to
      supervise their children's toothbrushings. Self-efficacy, planning, and action
      control are important self-regulatory skills in this context. Future
      interventions should map these self-regulatory predictors onto behaviour change
      techniques.

PMID- 29349926
TI  - Extracellular vesicles from early stage Plasmodium falciparum-infected red blood
      cells contain PfEMP1 and induce transcriptional changes in human monocytes.
AB  - Pathogens can release extracellular vesicles (EVs) for cell-cell communication
      and host modulation. EVs from Plasmodium falciparum, the deadliest malaria
      parasite species, can transfer drug resistance genes between parasites. EVs from
      late-stage parasite-infected RBC (iRBC-EVs) are immunostimulatory and affect
      endothelial cell permeability, but little is known about EVs from early stage
      iRBC. We detected the parasite virulence factor PfEMP1, which is responsible for
      iRBC adherence and a major contributor to disease severity, in EVs, only up to 12
      hr post-RBC invasion. Furthermore, using PfEMP1 transport knockout parasites, we
      determined that EVs originated from inside the iRBC rather than the iRBC surface.
      Proteomic analysis detected 101 parasite and 178 human proteins in iRBC-EVs.
      Primary human monocytes stimulated with iRBC-EVs released low levels of
      inflammatory cytokines and showed transcriptomic changes. Stimulation with iRBC
      EVs from PfEMP1 knockout parasites induced more gene expression changes and
      affected pathways involved in defence response, stress response, and response to
      cytokines, suggesting a novel function of PfEMP1 when present in EVs. We show for
      the first time the presence of PfEMP1 in early stage P. falciparum iRBC-EVs and
      the effects of these EVs on primary human monocytes, uncovering a new mechanism
      of potential parasite pathogenesis and host interaction.

PMID- 29349925
TI  - Ethanolamine is a valuable nutrient source that impacts Clostridium difficile
      pathogenesis.
AB  - Clostridium (Clostridioides) difficile is a gastrointestinal pathogen that
      colonizes the intestinal tract of mammals and can cause severe diarrheal disease.
      Although C. difficile growth is confined to the intestinal tract, our
      understanding of the specific metabolites and host factors that are important for
      the growth of the bacterium is limited. In other enteric pathogens, the membrane
      derived metabolite, ethanolamine (EA), is utilized as a nutrient source and can
      function as a signal to initiate the production of virulence factors. In this
      study, we investigated the effects of ethanolamine and the role of the predicted
      ethanolamine gene cluster (CD1907-CD1925) on C. difficile growth. Using targeted
      mutagenesis, we disrupted genes within the eut cluster and assessed their roles
      in ethanolamine utilization, and the impact of eut disruption on the outcome of
      infection in a hamster model of disease. Our results indicate that the eut gene
      cluster is required for the growth of C. difficile on ethanolamine as a primary
      nutrient source. Further, the inability to utilize ethanolamine resulted in
      greater virulence and a shorter time to morbidity in the animal model. Overall,
      these data suggest that ethanolamine is an important nutrient source within the
      host and that, in contrast to other intestinal pathogens, the metabolism of
      ethanolamine by C. difficile can delay the onset of disease.

PMID- 29349927
TI  - Treatment-related toxicities of immune checkpoint inhibitors in advanced cancers:
      A meta-analysis.
AB  - BACKGROUND: We performed a meta-analysis to quantify toxic death, adverse events
      (AEs) and treatment discontinuation due to AEs from checkpoint inhibitors (CI).
      METHODS: We searched for randomized trials with adequate reporting for toxicity
      outcomes. Pooled risk ratios were estimated for CI versus chemotherapy or
      different combinations of these agents. RESULTS: Twenty trials of five different
      cancers with 10 794 patients with performance status 0 or 1 were identified.
      Toxic deaths from CI were infrequent (0.6%). Treatment discontinuations were less
      frequent for programmed-death-1 (PD-1) or PD-ligand-1 (PD-L1) inhibitors (5.8% vs
      13.3%, P < 0.001) and cytotoxic-T-lymphocyte-associated-antigen-4 (CTLA-4)
      inhibitors (6.2% vs 11.4%, P = 0.002) than chemotherapy. PD-1/PD-L1 inhibitors
      had less grade 3, 4, and 5 (G3/4/5) AEs than chemotherapy (13.8% vs 39.8%, P <
      0.001) or CTLA-4 inhibitors (13.4% vs 22.8%, P < 0.001). Combination CI had
      higher discontinuation (37.8% vs 11.6%, P < 0.001) and higher G3/4/5 AEs (55.3%
      vs 21.9%, P < 0.001) than CI monotherapy. Endocrinopathy (11.2% vs 0.9%), rash
      (10.1% vs 4.3%) and pneumonitis (3.1% vs 0.7%) were associated with CI, and
      alopecia (25.9% vs 1.0%), neutropenia (16.6% vs 0.6%) and neuropathy (7.6% vs
      3.0%) with chemotherapy. CONCLUSIONS: CI inhibitors have different toxicity
      profiles to chemotherapy. These findings are useful for patient counselling and
      planning of future trials.

PMID- 29349928
TI  - Problem behaviours and psychotropic medication use in intellectual disability: a
      multinational cross-sectional survey.
AB  - BACKGROUND: Problem behaviours (PBs) are a common cause for clinician contact in
      people with disorders of intellectual development and may be a common cause for
      the prescription of psychotropic medication. We aimed to use a large,
      multinational sample to define the prevalence of PBs, the associations with
      psychotropic medication use, and to assess for any potential 'diagnostic
      overshadowing' by the label of PBs in a population of people with disorders of
      intellectual development. METHOD: A multinational, multi-setting, cross-sectional
      service evaluation and baseline audit was completed. Data were collected from UK
      hospitals, UK community settings, Sri Lanka and Hong Kong. A semi-structured
      questionnaire was completed by treating clinicians, capturing demographic
      details, prevalence rates of intellectual disability and psychotropic medication
      use, alongside psychiatric co-morbidity. RESULTS: A sample size of 358 was
      obtained, with 65% of included participants treated in an inpatient setting.
      Psychotropic use was prevalent (90%) in our sample, particularly antipsychotics
      (74%). The prevalence of PB was high (83%). There was no statistically
      significant association between psychotropic prescription and recorded
      psychiatric co-morbidity, suggesting prevalent 'off-label' use for PBs, or poor
      recording of psychiatric co-morbidity. There was some evidence of possible
      diagnostic overshadowing due to the PB classification. A higher dose of
      psychotropic medication was associated with aggression toward others (P = 0.03).
      CONCLUSIONS: We found evidence of prevalent potential 'off-label' use for
      psychotropic medication, which may be due to PBs. We also found evidence of
      potential diagnostic-overshadowing, where symptoms of psychiatric co-morbidity
      may have been attributed to PBs. Our findings provide renewed importance, across
      borders and health systems, for clinicians to consider a holistic approach to
      treating PBs, and attempting to best understand the precipitants and predisposing
      factors before psychotropic prescribing.

PMID- 29349930
TI  - Upcoming events of interest.

PMID- 29349929
TI  - Severity of cognitive disability and mental health court determinations about
      fitness to stand trial.
AB  - BACKGROUND: Little is known about the socio-demographic, clinical and legal
      determinants of mental health court decisions of unsoundness of mind and
      unfitness to stand trial for people with cognitive disability. We aimed to
      estimate the association between severity of cognitive disability and mental
      health court determinations of unsoundness or unfitness and describe the socio
      demographic, clinical and legal factors that predict these determinations.
      METHODS: Case file data were extracted on 92 individuals who had a criminal case
      referred to the Queensland Mental Health Court between 1 January 2013 and 31
      December 2014 due to cognitive disability. We fit a modified multivariable
      Poisson regression model to estimate the association between severity of
      cognitive impairment and mental health court determination, controlling for socio
      demographic, clinical and legal factors. RESULTS: Adjusting for covariate
      effects, severity of cognitive impairment was positively associated with being
      found unfit to stand trial (adjusted prevalence risk ratio = 1.57; 95% confidence
      interval: 1.07, 2.33; P = 0.023), and comorbid psychotic disorder predicted an
      increased risk of being found unsound of mind at the time of offence (adjusted
      prevalence risk ratio = 3.63; 95% confidence interval: 1.38, 9.54; P = 0.009) by
      the Queensland Mental Health Court. CONCLUSIONS: Severity of cognitive disability
      is associated with determinations of unfitness but does not predict
      determinations of unsoundness in the Queensland Mental Health Court. Psychiatric
      assessments of cognitive impairment play a pivotal role in mental health court
      determinations for people with cognitive disability.

PMID- 29349931
TI  - Biomimetic Architectures for Peripheral Nerve Repair: A Review of Biofabrication
      Strategies.
AB  - Biofabrication techniques have endeavored to improve the regeneration of the
      peripheral nervous system (PNS), but nothing has surpassed the performance of
      current clinical practices. However, these current approaches have intrinsic
      limitations that compromise patient care. The "gold standard" autograft provides
      the best outcomes but requires suitable donor material, while implantable hollow
      nerve guide conduits (NGCs) can only repair small nerve defects. This review
      places emphasis on approaches that create structural cues within a hollow NGC
      lumen in order to match or exceed the regenerative performance of the autograft.
      An overview of the PNS and nerve regeneration is provided. This is followed by an
      assessment of reported devices, divided into three major categories: isotropic
      hydrogel fillers, acting as unstructured interluminal support for regenerating
      nerves; fibrous interluminal fillers, presenting neurites with topographical
      guidance within the lumen; and patterned interluminal scaffolds, providing 3D
      support for nerve growth via structures that mimic native PNS tissue. Also
      presented is a critical framework to evaluate the impact of reported outcomes.
      While a universal and versatile nerve repair strategy remains elusive, outlined
      here is a roadmap of past, present, and emerging fabrication techniques to inform
      and motivate new developments in the field of peripheral nerve regeneration.

PMID- 29349932
TI  - Isolation and characterization of lectin with antibacterial, antibiofilm and
      antiproliferative activities from Acinetobacter baumannii of environmental
      origin.
AB  - AIMS: Lectin is a nonimmunogenic glycoprotein that has been extracted mostly from
      the primary plant source leguminoase. Its ability to precisely recognize and bind
      to the complex cell bound structure enables it to play diverse roles. In this
      study, we obligate to define new sources of lectins since the production of
      lectins is very expensive. Therefore, we performed a study with the goal to
      isolate and characterize lectin from bacteria of plant origin and screen its
      ability as an antibacterial, antibiofilm and antiproliferative agent. METHODS AND
      RESULTS: We investigated isolates of environmental origin for their ability to
      produce lectin using phenotypic and molecular detection. The lectin was purified
      from an isolate AB119 which has abundant lectin activity and its molecular weight
      was determined by SDS-PAGE and HPLC. This lectin has a molecular weight of 30 kD
      and used to evaluate its antimicrobial, antibiofilm and antiproliferative
      activities using earlier published protocols. All bacterial isolates tested in
      this study showed the ability to produce biofilm which was inhibited in the
      presence of lectin significantly. In microtitre plate assay, the scale of biofilm
      inhibition by the purified lectin was significantly reduced for all bacterial
      species. Lectin inhibited the growth of all three tested bacterial species after
      treatment for 24 h and this antimicrobial effect was uniform to all species
      irrespective of Gram positive or Gram negative. The antiproliferative effects of
      lectin against HeLa cells were determined using MTT assay showed significant
      inhibitory effects on the proliferation at an IC50 of 10 MUM for 24 h.
      CONCLUSION: This study concludes that lectin has a promising application as an
      antimicrobial and, antibiofilm agent to control multidrug-resistant pathogen
      associated infections. At the same time, it has also promising ability to control
      the proliferation of tumour cell as evident by our study results. SIGNIFICANCE
      AND IMPACT OF STUDY: AB119 lectin from A.baumannii species was verified for its
      capability to control microbial growth and its biofilm formation. Results showed
      lectin was able to reduce growth as well biofilm formation of both Gram-positive
      and Gram-negative bacterial species. Lectin has a promising application as an
      antibiofilm agent to combat the growing number of multidrug-resistant pathogen
      associated infections.

PMID- 29349933
TI  - Patient's specific integration of OAR doses (D2 cc) from EBRT and 3D image-guided
      brachytherapy for cervical cancer.
AB  - The objective of this study was to assess the recommended DVH parameter (e.g., D2
      cc) addition method used for combining EBRT and HDR plans, against a reference
      dataset generated from an EQD2-based DVH addition method. A revised DVH parameter
      addition method using EBRT DVH parameters derived from each patient's plan was
      proposed and also compared with the reference dataset. Thirty-one biopsy-proven
      cervical cancer patients who received EBRT and HDR brachytherapy were
      retrospectively analyzed. A parametrial and/or paraaortic EBRT boost were
      clinically performed on 13 patients. Ten IMRT and 21 3DCRT plans were determined.
      Two different HDR techniques for each HDR plan were analyzed. Overall D2 cc and
      D0.1 cc OAR doses in EQD2 were statistically analyzed for three different DVH
      parameter addition methods: a currently recommended method, a proposed revised
      method, and a reference DVH addition method. The overall D2 ccEQD2 values for all
      rectum, bladder, and sigmoid for a conformal, volume optimization HDR plan
      generated using the current DVH parameter addition method were significantly
      underestimated on average -5 to -8% when compared to the values obtained from the
      reference DVH addition technique (P < 0.01). The revised DVH parameter addition
      method did not present statistical differences with the reference technique (P >
      0.099). When PM boosts were considered, there was an even greater average
      underestimation of -8~-10% for overall OAR doses of conformal HDR plans when
      using the current DVH parameter addition technique as compared to the revised DVH
      parameter addition. No statistically significant differences were found between
      the 3DCRT and IMRT techniques (P > 0.3148). It is recommended that the overall D2
      cc EBRT doses are obtained from each patient's EBRT plan.

PMID- 29349934
TI  - Interleukin-34 levels in gingival crevicular fluid and plasma in periodontal
      health and disease with and without type-2 diabetes mellitus.
AB  - AIM: The aim of the present study was to evaluate and correlate the levels of
      interleukin-34 (IL-34) in gingival crevicular fluid (GCF) and plasma in chronic
      periodontitis (CP) patients with and without type-2 diabetes mellitus (DM).
      METHODS: A total of 175 patients were divided into five groups: (a) group I had
      35 periodontally-healthy patients; (b) group II had 35 chronic gingivitis
      patients; (c) group III had 35 CP patients without type-2 DM; (d) group IV had 35
      CP patients with type-2 DM; and (e) group V had 35 type-2 DM patients without CP.
      The GCF and plasma levels of IL-34 were quantified using enzyme-linked
      immunosorbent assay. Clinical and systemic parameters, such as gingival index,
      probing pocket depth, clinical attachment loss, and glycated hemoglobin levels,
      were evaluated. RESULTS: The mean IL-34 concentration in GCF and plasma was
      highest for group IV, followed by groups III, V, and II, and lowest in group I.
      The difference between them was statistically significant (P < .05). There was a
      positive correlation between IL-34 concentration in GCF and plasma in the study
      groups, with the exception of group I, for which there was a negative
      correlation. CONCLUSION: IL-34 can be considered a possible GCF and plasma
      inflammatory biomarker of periodontal disease progression and DM.

PMID- 29349936
TI  - Preeclampsia Increases the Incidence of Postpartum Cerebrovascular Disease in
      Korean Population.
AB  - BACKGROUND: Multiple studies have been reported regarding preeclampsia as a
      possible risk factor of cerebrovascular disease (CVD). However, the correlation
      of preeclampsia and CVD, whether it is a cause-effect relationship or they are
      sharing common predisposing condition, is not well understood. Therefore, the aim
      of this study was to investigate the association between the preeclampsia during
      pregnancy and development of postpartum CVD. METHODS: A total of 1,384,550 Korean
      women who had a delivery between January 1, 2010 and December 31, 2012, were
      enrolled. Women with the risk of CVD within 1 year prior to pregnancy were
      excluded based on the Charlson comorbidity index. Primary endpoint was the event
      of CVD within a year from delivery. After exclusion, 1,075,061 women were
      analyzed. RESULTS: During the follow-up of 1 year postpartum, there were 25,577
      preeclampsia out of 1,072,041 women without postpartum CVD (2.39%), and 121 of
      3,020 women with postpartum CVD had preeclampsia before delivery (4.01%). In
      multivariate logistic regression analysis, women who had preeclampsia during
      pregnancy showed a higher risk for postpartum CVD (odds ratio, 1.64; 95%
      confidence interval, 1.37-1.98). CONCLUSION: The incidence of CVD after delivery
      was higher in women who had preeclampsia during pregnancy.

PMID- 29349935
TI  - Pitfalls in the measurement of muscle mass: a need for a reference standard.
AB  - BACKGROUND: All proposed definitions of sarcopenia include the measurement of
      muscle mass, but the techniques and threshold values used vary. Indeed, the
      literature does not establish consensus on the best technique for measuring lean
      body mass. Thus, the objective measurement of sarcopenia is hampered by
      limitations intrinsic to assessment tools. The aim of this study was to review
      the methods to assess muscle mass and to reach consensus on the development of a
      reference standard. METHODS: Literature reviews were performed by members of the
      European Society for Clinical and Economic Aspects of Osteoporosis and
      Osteoarthritis working group on frailty and sarcopenia. Face-to-face meetings
      were organized for the whole group to make amendments and discuss further
      recommendations. RESULTS: A wide range of techniques can be used to assess muscle
      mass. Cost, availability, and ease of use can determine whether the techniques
      are better suited to clinical practice or are more useful for research. No one
      technique subserves all requirements but dual energy X-ray absorptiometry could
      be considered as a reference standard (but not a gold standard) for measuring
      muscle lean body mass. CONCLUSIONS: Based on the feasibility, accuracy, safety,
      and low cost, dual energy X-ray absorptiometry can be considered as the reference
      standard for measuring muscle mass.

PMID- 29349937
TI  - Changes in Clinical Characteristics of Patients with an Initial Diagnosis of
      Prostate Cancer in Korea: 10-Year Trends Reported by a Tertiary Center.
AB  - BACKGROUND: The Korea Central Cancer Registry reported that incidence rates of
      prostate cancer have not increased continuously. We used recent trends in the
      incidence of prostate cancer to generate a preliminary report of the Korean
      population with prostate cancer. METHODS: Patients initially diagnosed with
      prostate cancer by prostate biopsy from 2006 to 2015 at our tertiary center were
      selected. All patients were categorized according to age (< 65, 65-75, > 75
      years), time period (2006-2010 vs. 2011-2015), and risk classification. Patients
      with insufficient data were excluded from the analysis. RESULTS: Of 675 patients
      (median prostate-specific antigen [PSA], 9.09 ng/mL), those with a Gleason score
      (GS) of 6 (32.3%) comprised the largest proportion in our cohort. The proportion
      with a GS of 8 increased for those aged 65-75 years, despite the lack of increase
      in PSA. Treatment patterns changed for those with very low to low risk cancer.
      The overall survival (OS) rate and the cancer-specific survival (CSS) rate for
      all patients at 5 years were 87% and 90%, respectively. Patients with a low body
      mass index (BMI; <= 23 kg/m2) had worse median OS and CSS rates. CONCLUSION:
      Significant differences in risk classifications and initial treatments were found
      between 2006-2010 and 2011-2015. Although PSA did not change, the GS did change.
      Lower BMI (<= 23 kg/m2) had worse effects on OS and CSS rates for Korean prostate
      cancer patients.

PMID- 29349938
TI  - Improved Regional Disparities in Neonatal Care by Government-led Policies in
      Korea.
AB  - BACKGROUND: Although the number of high-risk neonates has increased in Korea,
      hospitals were reluctant to open or maintain neonatal intensive care unit (NICU)
      due to the low medical cost. Consequently, there were regional disparities in
      facilities, equipment, and neonatal health outcomes. For these reasons, the
      Korean government began to invest in neonatal care during the last decade. We
      identified the status of NICUs in Korea and assessed changes after the government
      driven policies. METHODS: We surveyed 87 of 89 hospitals that operated NICUs in
      2015. The questionnaire assessed the number of NICU beds, admission and mortality
      rates of very low birthweight infants (VLBWIs), personnel status, equipment and
      facilities, and available multidisciplinary approach. Current data was compared
      with the previous studies and changes in the status and function of the
      nationwide NICU from 2009 and 2011. RESULTS: During the last 7 years, there was
      an increase of 462 NICU beds, which met the required number estimated by the
      number of births and covered about 90% of regional VLBWI births. Status of
      facilities and equipment improved in all regions in Korea but there were still
      regional differences in multidisciplinary approach and human resources. The
      difference in odds ratios for mortality of VLBWI between regions decreased
      compared to 2009. CONCLUSION: There was improvement in regional disparities of
      neonatal care and mortality of premature babies with the government investment in
      Korea. Further supports are required for human resources and referral system.

PMID- 29349939
TI  - Comparison of District-level Smoking Prevalence and Their Income Gaps from Two
      National Databases: the National Health Screening Database and the Community
      Health Survey in Korea, 2009-2014.
AB  - BACKGROUND: We compared age-standardized prevalence of cigarette smoking and
      their income gaps at the district-level in Korea using the National Health
      Screening Database (NHSD) and the Community Health Survey (CHS). METHODS: Between
      2009 and 2014, 39,049,485 subjects participating in the NHSD and 989,292
      participants in the CHS were analyzed. The age-standardized prevalence of smoking
      and their interquintile income differences were calculated for 245 districts of
      Korea. We examined between-period correlations for the age-standardized smoking
      prevalence at the district-level and investigated the district-level differences
      in smoking prevalence and income gaps between the two databases. RESULTS: The
      between-period correlation coefficients of smoking prevalence for both genders
      were 0.92-0.97 in NHSD and 0.58-0.69 in CHS, respectively. When using NHSD, we
      found significant income gaps in all districts for men and 244 districts for
      women. However, when CHS was analyzed, only 167 and 173 districts for men and
      women, respectively, showed significant income gaps. While correlation
      coefficients of district-level smoking prevalence from two databases were 0.87
      for men and 0.85 for women, a relatively weak correlation between income gaps
      from the two databases was found. CONCLUSION: Based on two databases, income gaps
      in smoking prevalence were evident for nearly all districts of Korea. Because of
      the large sample size for each district, NHSD may provide stable district-level
      smoking prevalence and its income gap and thus should be considered as a valuable
      data source for monitoring district-level smoking prevalence and its
      socioeconomic inequality.

PMID- 29349941
TI  - Letter to the Editor: When Claiming a U-shaped Association between Uric Acid
      Levels and Major Adverse Cardiac Events, Perhaps Show the Evidence?

PMID- 29349940
TI  - Etiology of Invasive Bacterial Infections in Immunocompetent Children in Korea
      (2006-2010): a Retrospective Multicenter Study.
AB  - BACKGROUND: Invasive bacterial infections in apparently immunocompetent children
      were retrospectively analyzed to figure causative bacterial organisms in Korea.
      METHODS: A total of 947 cases from 25 university hospitals were identified from
      2006 to 2010 as a continuance of a previous 10-year period study from 1996 to
      2005. RESULTS: Escherichia coli (41.3%), Streptococcus agalactiae (27.7%), and
      Staphylococcus aureus (27.1%) were the most common pathogens in infants < 3
      months of age. S. agalactiae was the most prevalent cause of meningitis and
      pneumonia and E. coli was the major cause of bacteremia without localizing signs
      in this group. In children 3 to 59 months of age, Streptococcus pneumoniae
      (54.2%), S. aureus (20.5%), and Salmonella spp. (14.4%) were the most common
      pathogens. S. pneumoniae was the leading cause of pneumonia (86.0%), meningitis
      (65.0%), and bacteremia without localizing signs (49.0%) in this group. In
      children >= 5 years of age, S. aureus (62.8%) was the predominant pathogen,
      followed by Salmonella species (12.4%) and S. pneumoniae (11.5%). Salmonella
      species (43.0%) was the most common cause of bacteremia without localizing signs
      in this group. The relative proportion of S. aureus increased significantly over
      the 15-year period (1996-2010) in children >= 3 months of age (P < 0.001), while
      that of Haemophilus influenzae decreased significantly in both < 3 months of age
      group (P = 0.036) and >= 3 months of age groups (P < 0.001). CONCLUSION: S.
      agalactiae, E. coli, S. pneumoniae, and S. aureus are common etiologic agents of
      invasive bacterial infections in Korean children.

PMID- 29349942
TI  - Ancient Soil-Transmitted Parasite Eggs Detected from the Sixth Century Three
      Kingdom Period Silla Tomb.
AB  - The parasitic infection patterns of the Joseon period have begun to be revealed
      in a series of paleoparasitological studies. However, parasitism prevailing
      during or before the Three Kingdom period is still relatively unexplored. In the
      present study, we therefore conducted parasitological examinations of soil and
      organic-material sediments precipitated upon human hipbone and sacrum discovered
      inside an ancient Mokgwakmyo tomb dating to the Silla Dynasty (57 BCE-660 CE).
      Within the samples, we discovered ancient Ascaris lumbricoides (eggs per gram
      [EPG], 46.6-48.3) and Trichuris trichiura (EPG, 32.8-62.1) eggs, the species
      commonly detected among Korean populations until just prior to the 1970s. These
      findings show that soil-transmitted parasitic infection among the Silla nobility
      might not have been uncommon. This is the first-ever report on the presence of
      ancient parasite eggs in the samples obtained from a Three Kingdom period tomb;
      and it also presents the earliest positive results for any of the ancient South
      Korean tombs paleoparasitologically examined to date.

PMID- 29349943
TI  - Environmental and Body Concentrations of Heavy Metals at Sites Near and Distant
      from Industrial Complexes in Ulsan, Korea.
AB  - BACKGROUND: Industrial pollution may affect the heavy metal body burden of people
      living near industrial complexes. We determined the average concentrations of
      atmospheric heavy metals in areas close to and distant from industrial complexes
      in Korea, and the body concentrations of these heavy metals in residents living
      near and distant from these facilities. METHODS: The atmospheric data of heavy
      metals (lead and cadmium) were from the Regional Air Monitoring Network in Ulsan.
      We recruited 1,148 participants, 872 who lived near an industrial complex
      ("exposed" group) and 276 who lived distant from industrial complexes ("non
      exposed" group), and measured their concentrations of blood lead, urinary
      cadmium, and urinary total mercury. RESULTS: The results showed that atmospheric
      and human concentrations of heavy metals were higher in areas near industrial
      complexes. In addition, residents living near industrial complexes had higher
      individual and combined concentrations (cadmium + lead + mercury) of heavy
      metals. CONCLUSION: We conclude that residents living near industrial complexes
      are exposed to high concentrations of heavy metals, and should be carefully
      monitored.

PMID- 29349944
TI  - Investigation of Clinical and Pathological Relationships between Adult- and
      Pediatric-type NASH in Korean Children.
AB  - BACKGROUND: Histologically, nonalcoholic steatohepatitis (NASH) is categorized
      into adult-type (type 1) and pediatric-type (type 2). The origination of the
      histological difference between the two types and how they differ clinically
      remain uncertain. We aimed to understand the incidence and clinical
      characteristics of the two types of NASH in Korean children, and to investigate
      the association between their pathological type and clinical characteristics,
      using anthropometric and laboratory data. METHODS: In 38 children with confirmed
      NASH, we investigated hepatic pathological findings, and correlating factors
      between pathological type and laboratory and anthropometric data (weight
      percentile, body mass index (BMI) z-score, and blood pressure percentile). Adult
      type NASH was noted in 21 patients and pediatric-type in 17 patients. RESULTS:
      Age, sex, BMI, transaminase levels, and insulin resistance were not significantly
      different between the two groups. Triglyceride (TG) levels were higher in adult
      type NASH (P = 0.033). Hematocrit and albumin levels were lower in adult-type
      NASH (P = 0.016 and 0.013, respectively). Hepatic fibrosis was more common in
      pediatric-type. The fibrosis scores in patients with adult-type were mostly 0 and
      1, whereas the score was 3 in patients with pediatric-type (P = 0.024, 0.004, and
      < 0.010, respectively). Anthropometric data, liver function, and insulin
      resistance scores did not differ between the two pathological NASH types. TG,
      hematocrit, and albumin may be potential factors to predict pathological types.
      Fibrosis was observed more frequently in pediatric-type NASH. CONCLUSION:
      Monitoring children with pediatric-type NASH for progression to fibrosis or
      cirrhosis is recommended.

PMID- 29349945
TI  - The Within-Group Discrimination Ability of the Cancer of the Prostate Risk
      Assessment Score for Men with Intermediate-Risk Prostate Cancer.
AB  - BACKGROUND: Significant clinical heterogeneity within contemporary risk group is
      well known, particularly for those with intermediate-risk prostate cancer
      (IRPCa). Our study aimed to analyze the ability of the Cancer of the Prostate
      Risk Assessment (CAPRA) score to discern between favorable and non-favorable risk
      in patients with IRPCa. METHODS: We retrospectively reviewed the data of 203
      IRPCa patients who underwent extraperitoneal robot-assisted radical prostatectomy
      (RARP) performed by a single surgeon. Pathologic favorable IRPCa was defined as a
      Gleason score <= 6 and organ-confined stage at surgical pathology. The CAPRA
      score was compared with two established criteria for the within-group
      discrimination ability. RESULTS: Overall, 38 patients (18.7% of the IRPCa cohort)
      had favorable pathologic features after RARP. The CAPRA score significantly
      correlated with established criteria I and II and was inversely associated with
      favorable pathology (all P < 0.001). The area under the receiver operating
      characteristic curve for the discriminative ability between favorable and non
      favorable pathology was 0.679 for the CAPRA score and 0.610 and 0.661 for
      established criteria I and II, respectively. During a median 37.8 (interquartile
      range, 24.6-60.2) months of follow-up, 66 patients (32.5%) experienced
      biochemical recurrence (BCR). Cox regression analysis revealed that the CAPRA
      score, as a continuous sum score model or 3-group risk model, was an independent
      predictor of BCR after RARP. CONCLUSION: The within-group discrimination ability
      of preoperative CAPRA score might help in patient counseling and selecting
      optimal treatments for those with IRPCa.

PMID- 29349946
TI  - Validation Study of a Korean Version of the Abbreviated University of California,
      Los Angeles, PTSD Reaction Index (Abb-UCLA-PTSD RI) for Adolescents.
AB  - BACKGROUND: We aimed to verify a Korean version of the Abbreviated University of
      California, Los Angeles, Post-Traumatic Stress Disorder Reaction Index (Abb-UCLA
      PTSD RI-Korean version) among Korean adolescents to assess post-traumatic stress
      in this population. METHODS: We recruited 1,254 adolescents who completed the Abb
      UCLA-PTSD RI-Korean version scale, the Child Report of Post-Traumatic Symptoms
      (CROPS), the Lifetime Incidence of Traumatic Events (LITE), and the Children's
      Depression Inventory (CDI). Test-retest reliability was computed for a randomly
      selected 314 participants. Among all the students, 765 were included in the
      analysis because 143 students were classified in the normative group (LITE 1) and
      622 were in the traumatized group (LITE 4). RESULTS: The internal consistencies
      of the nine-item and eight-item versions of the Abb-UCLA PTSD RI-Korean version
      were found to be high (Cronbach's alpha = 0.843 and 0.842, respectively). The
      criterion-related validity was based on comparison of the Abb-UCLA PTSD RI total
      scores between the normative and trauma groups. For the eight-item version, the
      normative group (4.6 +/- 4.6) and the traumatized group (8.8 +/- 6.0)
      demonstrated better criterion-related validity than those in the nine-item
      version (4.5 +/- 4.3 and 8.5 +/- 5.0, respectively). The test-retest reliability
      of the eight-item version was better than the nine-item version (r = 0.85 vs.
      0.77). A two-factor model with eight items (two items regarding sleep, and the
      other six items made up the second factor) showed the best fit. CONCLUSION: Our
      results indicate that the eight-item Abb-UCLA PTSD RI-Korean version is a useful
      screening tool for post-traumatic stress in Korean adolescents.

PMID- 29349947
TI  - Incidence Rate of Atypical Femoral Fracture after Bisphosphonates Treatment in
      Korea.
AB  - BACKGROUND: Atypical femoral fracture (AFF) has been high-lightened, because it
      was associated with the long-term use of bisphosphonate. Comparing western
      countries, the incidence rate of AFF was unclear in East Asian patients. Our
      purposes were to estimate the incidence rate of radiologically defined AFF in
      Korea, and to determine the association between occurrence of AFF and long-term
      use of bisphosphonate. METHODS: We conducted a hospital-based, retrospective
      cohort study in patients aged >= 45 years, who took bisphosphonate. The
      occurrence of AFF was estimated by using incidence rate, and the age-adjusted
      incidence rate to U.S. 2010 Census data. The association between occurrence of
      AFF and the duration of bisphosphonate use was examined. The cumulative
      probability of AFF was plotted per each duration of bisphosphonate use. RESULTS:
      Among 10,338 individuals who took bisphosphonate, 13 patients with AFF following
      use of bisphosphonate were identified. The incidence rate was 85.9/100,000 person
      years (95% confidence interval [CI], 50.2-146.9), and age-adjusted incidence rate
      was 72.7/100,000 person-years (95% CI, 29.1-175.8). In Poisson regression
      analysis, higher body mass index (BMI) was associated with an increased risk of
      AFF (relative risk, 1.2; 95% CI, 1.004-1.359). The cumulative probability of AFF
      increased abruptly when the duration of bisphosphonate use was 4 years or more.
      CONCLUSION: Among Korean patients, the incidence rate of AFF was on a par with
      those of western countries, and this can provide basic information to conduct
      further studies by evaluating risk and benefit of continuing bisphosphonate.

PMID- 29349948
TI  - Case Report of Kidney Paired Donation (KPD) with Desensitization: the Strategy
      and Experience of 3-Way KPD in Samsung Medical Center.
AB  - As the need for the organ donation increases, strategies to increase kidney
      transplantation (KT) through expanded living donation have become essential.
      These include kidney paired donation (KPD) programs and desensitization in
      incompatible transplantations. KPD enables kidney transplant candidates with
      incompatible living donors to join a registry with other incompatible pairs in
      order to find potentially compatible living donor. Positive cross match and ABO
      incompatible transplantation has been successfully accomplished in selective
      cases with several pre-conditionings. Patients who are both difficult-to-match
      due to broad sensitization and hard-to-desensitize because of donor conditions
      can often be successfully transplanted through a combination of KPD and
      desensitization. According to the existing data, KPD can increase the number of
      KTs from living donors with excellent clinical results. This is also a cost
      effective treatment as compared with dialysis and desensitization protocols. We
      carried out 3-way KPD transplantation with one highly sensitized, positive cross
      match pair and with two ABO incompatible pairs. Herein we report our first
      successful 3-way KPD transplantation in a single center. To maximize donor
      recipient matching and minimize immunologic risk, KPD programs should use proper
      algorithms with desensitization to identify optimal donor with simultaneous two-,
      three- or more complex multi-way exchanges.

PMID- 29349949
TI  - Acute Spinal Subdural Hematoma in a Patient Taking Rivaroxaban.

PMID- 29349950
TI  - Issues and Solutions of Healthcare Data De-identification: the Case of South
      Korea.

PMID- 29349951
TI  - Tissue perfusion rate estimation with compression-based photoacoustic-ultrasound
      imaging.
AB  - Tissue perfusion is essential for transporting blood oxygen and nutrients.
      Measurement of tissue perfusion rate would have a significant impact in clinical
      and preclinical arenas. However, there are few techniques to image this important
      parameter and they typically require contrast agents. A label-free methodology
      based on tissue compression and imaging with a high-frequency photoacoustic
      ultrasound system is introduced for estimating and visualizing tissue perfusion
      rates. Experiments demonstrate statistically significant differences in depth
      resolved perfusion rates in a human subject with various temperature exposure
      conditions.

PMID- 29349952
TI  - Estimation of cerebral metabolic rate of oxygen consumption using combined
      multiwavelength photoacoustic microscopy and Doppler microultrasound.
AB  - The metabolic rate of oxygen consumption is an important metric of tissue oxygen
      metabolism and is especially critical in the brain, yet few methods are available
      for measuring it. We use a custom combined photoacoustic-microultrasound system
      and demonstrate cerebral oxygen consumption estimation in vivo. In particular,
      the cerebral metabolic rate of oxygen consumption was estimated in a murine model
      during variation of inhaled oxygen from hypoxia to hyperoxia. The hypothesis of
      brain autoregulation was confirmed with our method even though oxygen saturation
      and flow in vessels changed.

PMID- 29349953
TI  - [Concept of damage control and the choice of operative methods in the treatment
      of pelvic fractures].

PMID- 29349954
TI  - [Influence on coagulation function and the therapy effect of damage control
      orthopaedics for unstable pelvic fractures and multiple fractures of
      extremities].
AB  - OBJECTIVE: To retrospectively explore the effects of damage control orthopaedics
      concept on coagulation and curative effects in unstable pelvic fractures and
      multiple fractures of limbs. METHODS: From March 2014 to December 2015, 40
      patients with unstable pelvic fractures and limbs multiple fractures in treatment
      group included 22 males and 18 females with an average age of (39.00+/-4.12)
      years old were treated with the damage control orthopaedics concept, the ISS
      score was (25.36+/-10.81) on average;Other 40 patients with the same trauma in
      conventional group included 25 males and 15 females with an average age of
      (38.00+/-3.24) years old were treated with conventional method from January 2012
      to January 2014 served as control, the average ISS score was 26.56+/-11.44. Matta
      criteria and Majeed function standard were used respectively to evaluate the
      fracture reduction and therapeutic effects postoperatively. Coagulation function
      on the 7th day postoperatively was compared between two groups. RESULTS: All
      patients were followed up for 6 to 24 months. According to Matta criteria, the
      fracture reduction of the treatment group and the conventional group were (7.38+/
      5.09) mm and (10.11+/-6.53) mm, respectively (P<0.05). Majeed functional results
      of the treatment group and the conventional group were (86.12+/-6.84) points and
      (77.53+/-8.30) points, respectively (P<0.05). On the 7th day after surgery, PT,
      APTT, TT of the treatment group were significantly higher than that of the
      control group;and Fib of the treatment group was also significantly lower than
      that of the conventional group(P<0.05). CONCLUSIONS: The concept of damage
      control orthopaedics could effectively improve coagulation function of the
      patients with unstable pelvic fractures and limbs multiple fractures, thus are
      beneficial to the functional recovery as well as improve the curative effect
      postoperatively.

PMID- 29349955
TI  - [Clinical application of percutaneous iliosacral screws combined with pubic ramus
      screws in Tile B pelvic fracture].
AB  - OBJECTIVE: To investigate the application and effect of minimally invasive
      percutaneous anterior pelvic pubic ramus screw fixation in Tile B fractures.
      METHODS: A retrospective review was conducted on 56 patients with posterior
      pelvic ring injury combined with fractures of anterior pubic and ischiadic ramus
      treated between May 2010 and August 2015, including 31 males and 25 females with
      an average age of 36.8 years old ranging from 35 to 65 years old. Based on the
      Tile classification, there were 13 cases of Tile B1 type, 28 cases of Tile B2
      type and 15 cases of Tile B3 type. Among them, 26 patients were treated with
      sacroiliac screws combined with external fixation (external fixator group) and
      the other 30 patients underwent sacroiliac screw fixation combined with anterior
      screw fixation (pubic ramus screw group). Postoperative complications,
      postoperative ambulation time, fracture healing, blood loss, Majeed pelvic
      function score and visual analogue scale(VAS) were compared between two groups.
      RESULTS: Fifty-four patients were followed up from 3 to 24 months with a mean of
      12 months. There were no significant difference in the peri-operative bleeding
      and operation time between two groups(P>0.05). The postoperative activity time
      and fracture healing time of pubic ramus screw group were shorter than those of
      the external fixator group, the differences were statistically
      significant(P<0.05). The Majeed score, VAS score of pubic ramus screw group were
      higher than those of the external fixator group, the differences were
      statistically significant(P<0.05). The incidence of postoperative complications
      of pubic ramus screw was lower than that of the external fixator group, the
      difference was statistically significant (P<0.05). CONCLUSIONS: Percutaneous
      iliosacral screws fixation combined with the pubic ramus screw is an effective
      and safty treatment method to the Tile B pelvic fracture. It has advantages of
      early ambulation, relief of the pain and few complications.

PMID- 29349956
TI  - [Therapeutic observation of subcutaneous pedicle screw-rod system with modified
      placement for Tile B pelvic fractures].
AB  - OBJECTIVE: To investigate the feasibility and therapeutic effect of subcutaneous
      pedicle screw-rod system with modified placement in treatment of Tile B pelvic
      fractures. METHODS: From June 2014 to August 2015, 14 patients with Tile B pelvic
      fractures were treated by subcutaneous pedicle screw-rod system with modified
      placement in the anterior inferior iliac spine and pubic tubercle. There were 8
      males and 6 females, aged from 23 to 65 years with an average of 42 years.
      Operative time, intraoperative blood loss, fracture healing and postoperative
      complication were observed and clinical effects were evaluated by Matta reduction
      standard and Majeed score. RESULTS: All patients were followed up from 8 to 15
      months with an average of 10.5 months. Operative time was 25 to 45 min with an
      average of 32 min;intraoperative blood loss was 10 to 35 ml with an average of 18
      ml. All fractures got primary healing and healed time was 9 to 14 weeks with an
      average of 12.5 weeks. No postoperative incision infection, internal fixation
      failure and ectopic ossification were found, 4 cases occurred unilateral lateral
      femoral cutaneous nerve injury and 1 case occurred unilateral femoral nerve
      paralysis, but all restored finally. According to Matta criteria, reduction was
      excellent in 7 cases, good in 5 cases, fair in 2 case. According to Majeed score
      system, the functional evaluation at last follow-up was excellent in 5 cases,
      good in 7 cases, fair in 2 cases with the average score of 81.50+/-8.05.
      CONCLUSIONS: Subcutaneous pedicle screw-rod system with modified placement in the
      anterior inferior iliac spine and pubic tubercle have advantages of strong
      reduction, less trauma and complications, and is a promising surgical method in
      the treatment of Tile B pelvic fractures.

PMID- 29349957
TI  - [Choices of the internal fixation and approaches on unstable pelvic ring
      fractures].
AB  - OBJECTIVE: To discuss the suitable surgical approach and the internal fixation of
      unstable pelvic pelvic fractures. METHODS: From May 2010 to May 2015, 45 patients
      with unstable pelvic fractures were treated with different approaches and
      fixations, including 38 males and 7 females with an average age of 45 years
      ranging from 21 to 61 years. The course was within 2 weeks. According to Young
      Burg classification, 23 patients were lateral compression injuries, 6 patients
      were vertical shearing injuries, 16 patients were anterior-posterior compression
      injuries. All patients had hip pain and limitation of motion, the X-rays showed
      the pelvic ring fracture. RESULTS: All wounds healed well without complications,
      45 cases were followed up for a mean period of 13 months (ranged 9 to 21 months).
      Patients with hip pain had a good postoperative pain relief. The post-operative X
      rays showed the reduction was satisfied and the pelvic ring shaped well.
      According to Majeed standards, the final follow-up score was 93.5+/-11.6, 35
      cases got excellent results, 8 were good, 2 were fare. CONCLUSIONS: The unstable
      pelvic and acetabular fractures are always with compound injury. Beside the
      reduction, to decrease the second surgery trauma should take into consideration
      as well, the intra-articular reduction and the stability of the pelvic were
      especially valued, so combined the different approach with minimal invasive
      technique can get good clinical result.

PMID- 29349958
TI  - [Biomechanical analysis of the correlation between sacral tilt displacement and
      L5S1 disc degeneration].
AB  - OBJECTIVE: To biomechanical analysis of the correlation between sacral tilt
      displacement and L5-S1 disc degeneration. METHODS: From July 2011 to July 2013,
      81 patients with lumbar disc herniation and sacroiliac joint disorder including
      45 males and 36 females with an average age of (45.39+/-1.30) years ranging from
      18 to 65 years old were selected. The course of the disease ranged from 1 to 144
      months with an average of (12.64+/-2.19) months. All patients were taken lumbar
      spine lateral X-ray films, the lumbar curvature angle, L4-L5 or L5-S1
      intervertebral gap distance between points, and the lumbosacral angle was
      measured and correlated analyzed. RESULTS: The lumbar curvature of female
      patients with L5S1DH were significantly larger than male patients [(22.18+/-8.62)
      degrees  vs (16.17+/-4.97) degrees , P<0.05]. Lumbar curvature and lumbosacral
      angle showed a positive correlation in LDH (R=0.48, P<0.01,y=7.25+0.38x, P<0.01);
      Male patients with L4-5DH were more obvious (R=0.55, P<0.05, y=5.80+0.43x,
      P<0.01); Female patients with L5S1DH were particularly evident(R=0.74,
      P<0.01,y=0.91x-5.30, P<0.01). The lumbosacral angle and L4-5 intervertebral gap
      was a positive correlation in L4-5DH(R=0.27, P<0.05); While L5-S1 intervertebral
      gap and lumbosacral angle were not correlated(P>0.05) in L5S1DH. CONCLUSIONS: The
      sacral tilt displacement and L5-S1 disc degeneration were closely related to
      provide a new understanding philosophy and therapeutic approach for clinical
      treatment of intractable lumbar L5S1DH.

PMID- 29349959
TI  - [Comparison of the curative effect between over-elbow splint and traditional
      small splint fixation in the treatment of comminuted Colles fracture].
AB  - OBJECTIVE: To analyze the clinical efficacy of over-elbow small splint fixation
      for the treatment of comminuted Colles fractures. METHODS: From October 2013 to
      October 2015, 52 patients with comminuted Colles fracture were divided into two
      groups (the traditional splint fixation group and the over-elbow small splint
      fixation group) according to the treatment strategy. There were 26 patients in
      the over-elbow small splint fixation group including 7 males and 19 females with
      an average age of (64.615+/-11.475) years old ranging from 38 to 85 years old,
      and 26 patients in the traditional splint fixation group including 9 males and 17
      females with an average age of (65.269+/-13.162) years old ranging 36 to 91 years
      old, respectively. In the over-elbow small splint fixation group, 3 cases were
      type A3 fractures, 9 cases were type C1, 7 cases were type C2 and 7 cases were
      type C3;in the traditional splint fixation group, 4 cases were type A3, 8 cases
      were type C1, 9 cases were type C2 and 5 cases were type C3. After manipulative
      reduction, the fractures in traditional splint fixation group were fixed with
      traditional small splint, and the fractures in over-elbow small splint fixation
      group were added with over-elbow right angle splint for the first three weeks,
      then continued fixing like the control group until clinical cicatrization. All
      patients in both groups were regularly taken X-ray examination and changed
      dressings to obtain the clinical healing. Patients were guided to do functional
      exercise after splints were taken off. The therapeutic effects were evaluated
      according to modified Green and O'Brein score system after 8 weeks' functional
      exercise. RESULTS: All patients got clinical healing without severe complications
      in both groups. The shortened length of radius in traditional splint fixation
      group was more than that in over-elbow small splint fixation group (5.923+/
      1.978) mm VS (2.962+/-1.248) mm(P<0.05). There was no significant difference in
      radial incline between two groups. There was a higher wrist score in over-elbow
      small splint fixation group compared with traditional splint fixation group
      89.615+/-11.482 vs 80.385+/-13.485(P<0.05). CONCLUSIONS: Over-elbow small splint
      fixation is better than traditional splint fixation for the treatment of
      comminuted Colles fracture because of reliable clinical result and excellent
      wrist functional recovery.

PMID- 29349960
TI  - [Anterolateral acromial approach for the treatment of proximal humerus in 2-or 3
      part fractures-a case-control study].
AB  - OBJECTIVE: To explore the clinical curative effect of anterolateral acromial
      approach in treating two-and three-part of proximal humeral fractures. METHODS:
      Forty-two patients of proximal humeral fractures from January 2010 to June 2014
      were analyzed retrospectively, including 23 males and 19 females with a mean age
      of 61.5 years old ranging from 40 to 76 years old. Among them, 22 cases were
      treated with anterolateral acromial approach and 20 cases were treated with
      deltopectoral approach. The operation time, intraoperative blood loss,
      postoperative hospitalization days, fracture healing time of two groups were
      compared. The shoulder pain after 1 week was assessed by the VAS score. The
      postoperative shoulder joint function was evaluated after 3 months and more than
      6 months by Constant score. RESULTS: The follow-up time was at final 14 months.
      There were significant differences in operation time(P=0.003), intraoperative
      blood loss(P=0.001), postoperative hospital day(P=0.013), postoperative shoulder
      pain after 1 week(P=0.026), postoperative Constant score after 3 months(P=0.014)
      between the anterolateral acromial approach group and the deltopectoral approach
      group. There were no significant differences in clinical union time of
      bone(P=0.462), postoperative constant score after more than 6 months(P=0.204)
      between the anterolateral acromial approach group and the deltopectoral approach
      group. There were no breakage of the internal fixation and humeral head
      osteonecrosis. CONCLUSIONS: It has some advantages with anterolateral acromial
      approach to treat Neer two-and three-part of proximal humeral fractures, such as
      short operation time, less intraoperative bleeding, lighter postoperative pain,
      quicker recovery of function.

PMID- 29349961
TI  - [Total hip arthroplasty for post-traumatic arthritis after internal fixation of
      acetabular fracture].
AB  - OBJECTIVE: To study the clinical outcome of total hip arthroplasty(THA) for
      traumatic arthritis after acetabular fracture. METHODS: From June 2010 to June
      2014, 33 hips in 33 patients with traumatic arthritis after acetabular fracture
      were retrospective analyzed including 21 males and 12 females with a mean age of
      44.6 years old. All the patients received THA with bio-prostheses. Harris score
      was used to evaluate the hip function of patients before and after operation, the
      X-ray was adopted for radiographic evaluation of the hip prosthesis. RESULTS: All
      patients were followed up for 7 to 38 months with an average of 21.6 months. The
      Harris score increased from preoperative 53.6+/-2.4 to 94.0+/-3.0 at the final
      follow-up, the difference was statistically significant(t=55.37, P<0.05). The X
      ray evaluation showed the prosthesis was in good position, no loosening of the
      prosthesis, dislocation and periprosthetic osteolysis. CONCLUSIONS: THA is an
      effective treatment for the traumatic arthritis after acetabular
      fracture;internal fixation of acetabular fractures could not be removed if it
      shows difficult but does not affect the prosthesis placement.

PMID- 29349962
TI  - [Midterm clinical outcome for ankylosing spondylitis patients with early hip
      involved diseases treated with arthroscopic technique].
AB  - OBJECTIVE: To study the clinical outcome of manipulation release combined with
      arthroscopic debridement and synovia resection under general anesthesia for early
      hip involvment in patients with ankylosing spondylitis. METHODS: Manipulation
      release combined with arthroscpic debridement and synovium resection were
      performed for hip lesion in 22 patients with ankylosing spondylitis from June
      2011 to June 2013, incuding 6 males and 16 females with anverage age of 24.7
      years ranging from 17 to 23 years. The course of the diseases was from 10 to 41
      months(22.1 months on average). After 6 months of conservative treatment, hip
      pain and other symptoms were no relief. The preoperative and postoperative follow
      up evaluation was performed and compared by the hip movement, VAS pain score,
      mHHS score and NAHS score. RESULTS: All the patients were followed up for 26 to
      44 months with an average of 30.2 months. The range of motion in active flexion
      extension, abduction-adduction, internal-external rotation in 0 degrees  flexion
      and 90 degrees  flexion increased from (78.2+/-10.2) degrees , (36.3+/-6.4)
      degrees , (31.1+/-9.2) degrees  and (37.3+/-10.5) degrees  before operation to
      (113.5+/-8.4) degrees , (55.7+/-8.4) degrees , (58.7+/-2.1) degrees  and (60.1+/
      9.8) degrees  after operation, respectively. The VAS scores decreased from 8.5+/
      9.4 before operation to 5.5+/-7.1 after operation. The modified Harris and NAHS
      scores increased from 60.8+/-6.9 and 56.9+/-6.25 before operation to 88.1+/-10.4
      and 84.6+/-5.4 after operation, respectively. CONCLUSIONS: Manipulation release
      combined with arthroscopic debridement and synovium resection under general
      anesthesia could effectively control the progression of hip lesion in patients
      with ankylosing spondylitis restoring the ROM, relieve pain symptoms, delay joint
      deformity and ankylosis with less bleeding, faster recovery, and significantly
      improve patients' quality of life.

PMID- 29349963
TI  - [Research on the stability of teaching robots of rotation-traction manipulation].
AB  - OBJECTIVE: To evaluate the stability of teaching robot of rotation-traction
      manipulation. METHODS: Operators were required to get the hang of rotation
      traction manipulation and had clinical experience for over 5 years. The
      examination and data processing of the ten operators in our research were
      collected by the teaching robot of rotation-traction manipulation. Traction,
      pulling force, maximum force, pulling time, rotational amplitude and pitch range
      were recorded and compared for five times(G1, G2, G3, G4 and G5). The
      qualification rates were analyzed to evaluate the stability of teaching robot of
      rotation-traction manipulation. RESULTS: Nonconforming items were found in G1 and
      G2, for instance, pulling force(P=0.074), maximum force(P=0.264) and rotational
      amplitude (P=0.531). There was no statistically difference. None nonconforming
      item was found in G3, G4 and G5. All data were processed by SPSS and One-way
      ANOVA was used to analysis. Pulling force was found statistically different in
      G1, compared with G4 and G5(P=0.015, P=0.006). Maximum force was found
      statistically different in G1, compared with G4 and G5 (P=0.021, P=0.012). None
      differences were found in other comparisons (P>0.05). CONCLUSIONS: The teaching
      robot of rotation-traction manipulation used in our research could provide
      objective and quantitative indices and was considered to be an effective tool of
      assessing the rotation-traction manipulation.

PMID- 29349964
TI  - [Biomechanical study of the lateral wall of the femur in the treatment of femoral
      intertrochanteric fracture with intramedullary or extramedullary fixation].
AB  - OBJECTIVE: To observe the biomechanical effects of the lateral wall of the femur
      in treating femoral intertrochanteric fractures with intramedullary or
      extramedullary fixation to guide the choice of clinical fixed methods. METHODS:
      Twelve adults femur specimens of intertrochanteric fractures were belong to the
      type A1 of the AO fracture classification and randomly divided into the lateral
      wall complete PFNA group, the lateral wall complete PF-LCP group, the lateral
      wall breakage PFNA group, lateral wall breakage PF-LCP group, every group had 3
      specimens. The four groups of specimens were subjected to compressive loading
      experiment with Universal Material Testing Machine. The maximum loading force was
      observed. The distance between fracture ends, the distance of fracture
      dislocation and the sliding distance of the fracture fragments along the
      intertrochanteric were measured with Calipers. RESULTS: The maximum loading force
      of lateral wall complete PFNA group were larger than that of lateral wall
      complete PF-LCP group, and the maximum loading force of lateral wall breakage
      PFNA group were larger than that of lateral wall breakage PF-LCP group, there
      were significant differences (P<0.05). The distance between fracture ends of the
      four groups before compression were not significant differences(P>0.05). The
      distance between fracture ends, the distance of fracture dislocation and the
      sliding distance of the fracture fragments were not significant differences
      between lateral wall complete PFNA group and lateral wall complete PF-LCP group
      after compression (P>0.05). But the distance between fracture ends, the distance
      of fracture dislocation and the sliding distance of the fracture fragments of
      lateral wall breakage PFNA group were less than that of lateral wall breakage PF
      LCP group(P<0.05). CONCLUSIONS: Intramedullary fixation of intertrochanteric
      fractures have stronger loading force. Both intramedullary and extramedullary
      fixation of intertrochanteric fractures have strong stability when the lateral
      wall of the femur is complete, but intramedullary fixation of intertrochanteric
      fractures is stronger stability than extramedullary fixation when the lateral
      wall of the femur is broken. So the intramedullary fixation is the first choice
      for the treatment of intertrochanteric fracture.

PMID- 29349965
TI  - [Clinical characteristics analysis of lumbar disc herniation with symptom
      aggravated caused by spinal manipulative therapy].
AB  - OBJECTIVE: To discuss the characteristics of lumbar disc herniation (LDH) with
      symptom aggravated caused by spinal manipulative therapy (SMT). METHODS: Detailed
      clinical profiles of a total number of 10 LDH patients with symptoms aggravated
      after SMT were reviewed including 5 males and 5 females with age from 46 to 68
      years old, 7 patients of them were more than 50 years old. The clinical data of
      10 patients were analyzed involving age, gender, clinical symptoms, signs,
      imaging findings, surgical treatment and prognosis. Laminectomy and discectomy
      were performed, and follow-up was carried out in all patients. RESULTS: The
      duration of symptoms in all the patients before SMT was 4 to 15 years. After the
      therapy, an acute exacerbation of back and radicular pain was observed within 24
      hours. MRI showed intervertebral disc herniation, 7 patients were observed in L4
      L5. The time internal between the exacerbation of presentation and surgery was
      23.1 days. No perioperative complications occurred. All the patients were
      relieved of radicular pain a few days after surgery. During postoperative follow
      up, all patients regained the ability to walk; Eight patients reported a complete
      resolution of presentation and the rest two patients were significantly improved.
      CONCLUSIONS: SMT should be prohibited in some LDH patients to prevent
      neurological damages, in whom there are 5 possible risk factors.

PMID- 29349966
TI  - [A medium term therapeutic effects of anatomic locking plate for femoral
      intertrochanteric with lateral femoral wall fractures].
AB  - OBJECTIVE: To retrospectively study medium term follow-up outcomes of the femoral
      intertrochanteric with lateral femoral wall fractures using anatomic locking
      plate fixation. METHODS: From June 2010 to January 2013, 18 cases of the unstable
      femoral intertrochanteric with lateral femoral wall fractures were treated with
      the anatomic locking plate, included 8 males and 10 females with an average age
      of 75.5 years ranging from 19 to 83 years old. There were 8 cases of traffic
      accident injuries, 6 cases of falls injuries, and 4 cases of falling from high
      place. The time from injury to operation was ranged from 1 to 14 days with an
      average of 4.5 days. The operation time, intraoperative blood loss and the length
      of hospitalization were recorded and analyzed. The fracture union was assessed by
      follow-up radiographs and hip functional recovery by PPMS and Harris hip scoring.
      RESULTS: All patients were followed up from 36 to 68 months with a mean of(44.8+/
      8.8) months. The mean operative time was (61.02+/-38.28) min;the mean blood loss
      was (226.00+/-162.52) ml;the mean length of hospitalization was (10.8+/-9.2)
      days. During the follow-up period, no infection, deep veintllrombosis, screwed
      cut-out and implant failure occurred in all patients. Coxa vara with shortening
      deformity was noted in 2 cases. Bone union was found in all the cases. The bone
      healing time was ranged from 4 to 10 months with an average of 6.2 months. The
      mean PPMS score at the final follow-up was 7.22+/-2.36. The Harris score was
      79.46+/-11.02, 5 cases were classified as excellent, 9 as good and 2 as fair.
      CONCLUSIONS: Proximal femoral anatomic locking plate can be used in treating
      intertrochanteric fractures with compromised lateral wall, which has a satisfied
      medium term follow-up outcomes, especially for complex fractures patterns in
      which intramedullary nailing may be difficult, and should not emphasis on
      premature loading.

PMID- 29349967
TI  - [Treatment of children with femoral subtrochanteric fractures by the external
      fixation combined with single hip plaster].
AB  - OBJECTIVE: To explore curative effects of external fixation combined with single
      hip plaster in treating children with femoral subtrochanteric fracture. METHODS:
      Form March 2009 to July 2016, 15 children with femoral subtrochanteric fracture
      were treated with external fixation combined with single hip plaster, including 9
      males and 6 females with a mean age of 8.5 years old ranging from 5 to 14 years
      old. According to fracture classification of Seinsheimer, 3 cases were type IIA,
      4 cases were type IIB, 3 cases were type IIC, 2 cases were type IIIA, 1 case was
      type IIIB, 1 case was type IV, 1 case was type V. Complications and radiographs
      were retrospectively reviewed. Postoperative function of hips were evaluated
      according to Sanders criteria. RESULTS: All children were followed up from 16 to
      48 months with an average of 32 months. No early closure of epiphysis, bone
      nonunion and breakage of screw occurred. According to the Sanders score standard
      of hip function, the result was excellent in 14 cases, good in 1 case. There were
      no hip inversion, limb shortening, excessive growth and other malformations.
      CONCLUSIONS: External fixation combined with single hip plaster for the treatment
      of children is a safe and effective fixation, which provide a new choice of
      femoral subtrochanteric fracture.

PMID- 29349968
TI  - [Clinical outcomes of total hip arthroplasty using Wagner SL revision stem in
      femoral intertrochanteric fractures for patients with old fracture or painful
      arthritis before injury].
AB  - OBJECTIVE: To retrospectively study the clinical results of total hip
      arthroplasty(THA) using Wagner SL revision stem for patients with femoral
      intertrochanteric fracture. METHODS: From 2006 January to 2009 December, 29
      consecutive patients with femoral intertrochanteric fractures were performed THA
      using Wagner SL revision stem and intertrochanteric reconstruction, including 18
      males and 11 females with an average age of 49 years old ranging from 43 to 58.
      Among them, 8 cases were oboslete femoral intertrochanteric fractures and 21
      cases were the intertrochanteric fractures with painful arthritis before
      injuries. After the operation, the follow-up results were evaluated with clinical
      and radiographic criteria. The clinical follow-up results were evaluated by
      Harris score, limb length discrepancy, ROM of hips and the strength of the hip
      abductor. The X-ray imaging follow-up results were evaluated by periprosthetic
      osteolysis, prosthesis loosening and radiolucent. RESULTS: All the operations
      were successfully completed without serious complications associated with THA.
      Twenty-nine cases were followed up for a mean duration of 8.2 years (ranged, 6 to
      10). There was no acceptable thigh pain. The first time walk after operation, 8
      patients with oboslete intertrochanteric fracture complained the surgical sides
      were longer, with the passage of time, the complaint significantly reduced. At 3
      months after operation, X-ray films of 21 cases showed intertrochanteric
      fractures healed well who had painful arthritis before injuries. An average of 6
      months after operation (ranged, 3 to 8), X-ray films of 8 cases of oboslete
      intertrochanteric fracture showed that the bone graft and trochanter with obvious
      callus connection. There were no obvious prosthesis subsidence on X-ray film at
      the final follow-up. The recovery of hip movement range was satisfactory, no hip
      abduction strength was weak. More than 6 years after the operation, according to
      the Harris scoring evaluation of hip joint, the result was excellent in 18 cases,
      good in 9 cases, general in 2 cases. CONCLUSIONS: The clinical results of total
      hip arthroplasty using Wagner SL revision stem for patient with femoral
      intertrochanteric fracture is a reliable method, intertrochanteric reconstruction
      not only makes for prosthesis and joint stability, but also increases bone
      reserve.

PMID- 29349969
TI  - [Early application of the antibiotic-laden bone cement (ALBC) combined with the
      external fixation support in treating the open fractures of lower limbs
      complicated with bone defect].
AB  - OBJECTIVE: To discuss the curative effect of the early application of the
      antibiotic-laden bone cement (ALBC) combined with the external fixation support
      in treating the open fractures of lower limbs complicated with bone defect.
      METHODS: From December 2013 to January 2015, 36 cases of lower limb open
      comminuted fractures complicated with bone defects were treated by the vancomycin
      ALBC combined with the external fixation support, including 26 males and 10
      females with an average age of 38.0 years old ranging from 19 to 65 years old.
      The included cases were all open fractures of lower limbs complicated with bone
      defects with different degree of soft tissue injuries. Among them, 25 cases were
      tibial fractures, 11 cases were femoral fractures. The radiographs indicated a
      presence of bone defects, which ranged from 3.0 to 6.1 cm with an average of 4.0
      cm. The Gustilo classification of open fractures:24 cases were type IIIA, 12
      cases were typr IIIB. The percentage of wound infection, bone grafting time,
      fracture healing time and postoperative joint function of lower limb were
      observed. The function of injured limbs was evaluated at 1 month after the
      clinical healing of fracture based on Paley evaluation criterion. RESULTS: All
      cases were followed up for 3 to 24 months with an average of (6.0+/-3.0) months.
      The wound surface was healed well, neither bone infections nor unhealed bone
      defects were presented. The reoperation of bone grafting was done at 6 weeks
      after the patients received an early treatment with ALBC, some of them were
      postponed to 8 weeks till the approximate healing of fractures, the treatment
      course lasted for 4 to 8 months with an average of(5.5+/-1.5) months. According
      to Paley and other grading evaluations of bone and function, there were 27 cases
      as excellent, 5 cases as good, 3 cases as ordinary. CONCLUSIONS: The ALBC
      combined with external fixation support was an effective method for early
      treatment to treat the traumatic lower limb open fractures complicated with bone
      defects. This method was typified with the advantages such as easy operation,
      short operation time, overwhelming superiority in controlling infection and
      provision of good bone grafting bed, a good bone healing can be realized by the
      use of membrane induction technology for bone grafting.

PMID- 29349970
TI  - [Total thigh musculocutaneous flap in reconstruction of refractory pressure
      ulcers around hips in patients with spinal cord injury].
AB  - OBJECTIVE: To discuss the treatment of life-threatening refractory pressure
      ulcers around hips in patients with spinal cord injuries(SCI)and evaluate its
      clinical outcomes. METHODS: From March 2012 to June 2015, eight paraplegic
      patients with life-threatening refractory pressure ulcers around hips were
      treated with total thigh musculocutaneous flaps following amputation of proximal
      femurs or hips, including 7 males and 1 female with an average age of (52.0+/
      2.6) years old ranging from 35 to 68. The coures of disease was from 10 months to
      7 years with a mean of(2.9+/-0.2) years. All the 8 patients had compound ulcers
      of more than two parts, 7 cases had hip infection on the same side. The area of
      superficial wounds ranged from 3.0 cm*3.0 cm to 12.0 cm*15.0 cm. The clinical
      effects were evaluated according to infection controlling, wound healing,
      improving of nutrition and life quality of patients. RESULTS: All patient were
      followed up for 3 months to 2 years with an average of 1.3 years. All flaps
      survived, 5 cases obtained wound healing at one-stage, 2 cases had wound
      dehiscence and the wounds were closed after a second operation, 1 case had
      partial flap necrosis which was healed by dressing change, 1 case had urethral
      injury that was repaired in operation. All wounds were cured successfully without
      infection and ulcer recurrence during the follow-up period. The nutrition and
      quality of life of all cases improved observably after operation. CONCLUSIONS:
      The total thigh musculocutaneous flap is effective to reconstruct the refractory
      pressure ulcers around hip of patient with SCI. It can rescue life at the cost of
      losing one lower limb. It is an operation of last resort for the patients.

PMID- 29349971
TI  - [Intraosseous lipoma: retrospective analysis of 19 patients].
AB  - OBJECTIVE: To investigate the diagnostic and therapeutic procedures of
      intraosseous lipoma. METHODS: From June 1986 to January 2016, 19 patients with
      intraosseous lipoma were treated including 12 males and 7 females, aged from 24
      to 76 years, a predilection aged was from 40 to 50 years in 13 cases. Symptoms
      presented with pain or swelling in 15 patients, the lesions were found
      incidentally in 3 patients, another case was bone defect lipoma replacement after
      curettage of bone cyst for 4 years. On plain X-ray flims of all bones showed a
      well-circumscribed radiolucent area. Diagnosis was established with CT or MRI.
      Among them, 16 cases were treated by surgical operation, 3 cases were treated by
      concervative treatment. All patients' clinical data, histologic findings and X
      ray, CT and MRI were analysed. RESULTS: Total 19 patients were followed up from 9
      to 42 months with an average of 15 months. There was no local tumor recurrence in
      16 patients after excising the tumors, the remaining 3 patients showed no
      enlargement of the lesion. CONCLUSIONS: Surgical intervention is considered as an
      unnecessary in the patients diagnosied intraosseous lipoma by MRI or CT. Patients
      with symptomatic should adopt surgical treatment with curettage and bone
      grafting.

PMID- 29349972
TI  - [Current therapy progress on the recurrent patellar dislocation].
AB  - Patients who suffer from the recurrent patellar dislocation mainly show the
      recurrent dislocation of patellar, giving way, most patients have the history of
      trauma or dysplasia of keen joint. Traditional therapies of recurrent patellar
      dislocation include medical retinaculum placation, lateral retinaculum release,
      tibial tubercle osteotomy, femoral trochleoplasty etc. In recent years, with the
      development of anatomical and biomechanical researches on medial patellofemoral
      ligament(MPFL), more and more experts focus on the role of MPFL played in
      preventing the patellar dislocation. The treatment of recovering and correcting
      patellar tracking through MPFL reconstruction has been increasing gradually.
      However, till now, there was no therapy which could heal the recurrent patellar
      dislocation completely. The specific therapies of recurrent patellar dislocation
      are combination therapies, decided according to the anatomical and biomechanical
      conditions of patients, for recovering the stability of patients' patellar, the
      lower limb alignment and the function of keen-joint.

PMID- 29349973
TI  - [Progress on surgical treatment for femoral head-preservering in the precollapse
      stage of femoral head necrosis].
AB  - Osteonecrosis of the femoral head(ONFH), a refractory disease characterized by
      death of the osteocytes and the bone marrow due to inadequate blood supply caused
      by various mechanisms, usually leads to the collapse of the femoral head and
      malfunction of the hip joint. The crux is to diagnose ONFH early in the
      precollapse stage and prevent subsequent progression of collapsing through early
      interventions, thus delaying or avoiding the replacement of the hip joint. A
      number of joint salvaging operation treatments for early stage ONFH are
      available. However, there has been no consensus with regard to the ideal
      treatment. The main trend now is to unite core decompression with bone-grafting,
      tantalum rod, bone marrow mesenchymal stem cell (BMSC) and other treatments. Also
      there are ways of osteotomy altering the angle of the femoral neck to relocate
      necrotic tissue from the weight-bearing segment. The implanting of tantalum rod
      remains controversial and the advent of bone marrow mesenchymal stem cell (BMSC)
      holds huge potential.

PMID- 29349974
TI  - [Improvement of arthroscopic thecnique to be helpful for the accurate treatment
      of knee joint injury].

PMID- 29349975
TI  - [Clinical research on the arthroscopic treatment for recurrent patellar
      dislocation by anatomical reconstruction of medial patellarfemoral ligament].
AB  - OBJECTIVE: To observe the therapeutic effects of arthroscopic treatment for
      recurrent patellar dislocation by anatomical reconstruction of medial
      patellarfemoral ligament. METHODS: From June 2009 to December 2014, 25 patients
      with recurrent patellar dislocation were treated with anatomical reconstruction
      of medial patellarfemoral ligament surgery under arthroscopy. There were 10 males
      and 15 females, with an average age of 18.4 years old (ranged, 15 to 25 years old
      ). There were 15 patients who had a medical history of sports injury, 7 patients
      had a chronic impairment history, and the other 3 patients had the symptoms
      without obvious predisposing causes. Fourteen patients had injuries on the right
      knee and 11 patients had injuries on the left knee. All the patients suffered
      from patellar dislocation 3 to 10 times. After operation, the exercise of knee
      joint were performed postoperatively. The knee range of motion, Lysholm score,
      Kujala score, Insall criteria, Patellar apprehension test and patellar grinding
      test were observed to evaluate the clinical effects. RESULTS: All the patients
      were followed up, and the duration ranged from 12 to 48 months, with an average
      of 24.8 months. After surgery, all the wounds were healed excellent and there
      were no complications like surgical incision infection or patellar redislocation.
      The ranges of motion was increased from preoperative (105.40+/-5.93) degrees  to
      postoperative(122.60+/-5.42) degrees . At the latest follow-up, the Lysholm
      scores were increased from preoperative 64.12+/-7.49 to postoperative 91.44+/
      5.53, the Kujala scores were increased from preoperative 57.88+/-5.10 to
      postoperative 92.44+/-2.69. According to the Insall criteria, 19 patients got an
      excellent result, 5 good and 1 fair. CONCLUSIONS: It has a satisfactory clinical
      therapeutic effect on anatomical reconstruction of medial patellarfemoral
      ligament under arthroscopy for the treatment of recurrent patellar dislocation.
      It is helpful for the relief of clinical symptoms and improvement of knee joint
      function.

PMID- 29349976
TI  - [Analysis on the arthroscopy efficacy with different irrigation times for the
      treatment of suppurative knee arthritis in elder patients].
AB  - OBJECTIVE: To evaluate the curative effect of arthroscopy-assisted irrigation
      with different times for the treatment of suppurative knee arthritis in elder
      patients. METHODS: From October 2012 to October 2014, 23 old patients with
      suppurative knee arthritis were treated with arthroscopic debridement and
      continuous irrigation. All the patients were randomly divided into two groups:one
      week irrigation group (10 cases) and two-week irrigation group(13 cases). The
      ESR, CRP, recovery time of knee skin temperature, joint rang of motion and knee
      function were observed to evaluate the therapeutic effects. RESULTS: All the
      patients were followed up, and the mean duration was(13.3+/-2.3) months. No
      recurrence was observed. The CRP in both groups returned to normal level 2 weeks
      after operation. The ESR in two-week irrigation group returned to normal level 2
      weeks after operation, while in one-week irrigation group it was still at a high
      level, and returned to normal level 3 weeks after operation; there was a
      statistical significance between these two groups(P<0.05). The recovery time of
      knee skin temperature after operation in two-week irrigation group was (13.4+/
      1.2) d on average(ranged, 8 to 17 d), which was less than(15.5+/-1.9) d on
      average(ranged, 10 to 20 d) in one-week irrigation group (P<0.05). The knee joint
      mobility of all patients 1, 3, 6 months after operation was significantly
      improved compared with those before surgery(P<0.05). The knee joint mobility of
      patients in two-week irrigation group was better than that in one-week irrigation
      group at the first month after operation(P<0.05);but there were no significant
      differences between these two groups 3, 6 months after operation. The Lysholm
      score of all patients 1, 3, 6 months after operation was significantly improved
      compared with those before surgery(P<0.05). The Lysholm score of patients in two
      week irrigation group was better than in one-week irrigation group at the first
      month after operation(P<0.05);but there were no significant differences between
      these two groups 3, 6 months after operation. All the patients had stable knee
      functions 3 months after operation. According to the Lysholm scale, 3 patients
      got an excellent result, 6 good and 1 poor in one-week irrigation group 6 months
      after operation;5 patients got an excellent result, 7 good and 1 poor in two-week
      irrigation group;there was no significant differences between these two groups.
      CONCLUSIONS: Treatment of suppurative knee arthritis using arthroscopy has such
      advantages as minimal invasion and complete debridement, which is helpful to
      attenuate inflammation and regain knee function. It is suggested that the
      irrigation should be prolonged for two weeks postoperatively.

PMID- 29349977
TI  - [Therapeutic effects of internal drainage by expanding arthroscopic gastrocnemius
      semimembranosus bursa and cyst wall resection for the treatment of 41 patients
      with popliteal cysts].
AB  - OBJECTIVE: To investigate the clinical curative effects of internal drainage by
      expanding arthroscopic gastrocnemius-semimembranosus bursa(GSB) and cyst wall
      resection for the treatment of popliteal cysts. METHODS: A retrospective analysis
      of patients from May 2011 to December 2015. Arthroscopic treatment for 41
      patients with popliteal fossa cysts, 18 males and 23 females, aged from 34 to 67
      years old, averaged 42.6 years old. All the patients had preoperative magnetic
      resonance imagings to confirm the diagnosis and identify the valvular
      opening(Gastrocnemius-Semimembranosus bursa, GSB), as well as the associated
      intra-articular pathology. All the popliteal cysts were unilateral, including 26
      cases of right knees and 15 cases of left knees. Five patients had recurrent
      popliteal cysts, and all of them underwent initial open Surgery. The duration
      from initial surgery to the recurrence ranged from 6 to 17 months(averaged, 11
      months). All the patients had underwent arthroscopic treatment of internal
      drainage by expanding GSB and cyst wall resection. According to the Rauschning
      and Lindgren classification, 5 cases were grade I , 30 cases were grade II and 6
      cases were grade III. Preoperative Lysholm score, 83.19+/-6.12 (ranged form 73 to
      95). RESULTS: The GSB structure was found in all patients with popliteal cysts
      during operation, including cartilage degeneration in 33 cases, medial meniscus
      injury in 27 cases, lateral meniscus injury in 7 cases, free body in 8 cases,
      pigmented villonodular synovitis in 2 cases, and synovial chondromatosis in 3
      cases. There were no complications related to vascular, nerve or surgical
      incision. All the patients were followed up, and the duration ranged from 8 to 27
      months, with an average of 18 months. No recurrence of cysts was found. According
      to the Rauschning and Lindgren classification, there were 9 cases of grade 0, 27
      cases of grade I , 4 cases of grade II, 1 case of grade III. Postoperative
      Lysholm score:91.32+/-4.26(ranged from 82 to 98). CONCLUSIONS: Arthroscopic
      internal drainage by expanding GSB and cyst wall resection surgery in the
      treatment of popliteal cysts has the advantages of less trauma, faster recovery
      and low relapse rate, which has a good short-term effect.

PMID- 29349978
TI  - [Correlation of medial compartmental joint line elevation with femorotibial angle
      correction and clinical function after unicompartmental arthroplasty].
AB  - OBJECTIVE: To study the correlation of postoperative femorotibial angle with
      medial compartmental joint line elevation after unicompartmental
      arthroplasty(UKA), as well as the correlation of joint line elevation with the
      clinical function by measuring radiological joint line. METHODS: A retrospective
      study of 56 patients from July 2012 to August 2015 was performed. The mean body
      mass index (BMI) was 23.5 (ranged, 18.3 to 30.1). The standing anteroposterior
      radiographs of these patients were assessed both pre-and post-operatively, and
      the knee function was evaluated according to HSS grading. The correlation between
      postoperative femorotibial angle(FTA) and joint line elevation was analyzed as
      well as the correlation between joint line elevation and the clinical function.
      RESULTS: The mean medial joint line elevation was (2.2+/-2.0) mm(ranged, -3.3 to
      7.0 mm), and the mean FTA correction was (2.3+/-3.0) degrees (ranged, -4.5
      degrees  to 9.6 degrees ). The mean follow-up period was 12.2 months. There was a
      significant correlation between in joint line elevation and FTA
      correction(P<0.05), while there was no significant correlation between joint line
      elevation and the clinical function(P>0.05). CONCLUSIONS: There was a significant
      correlation between medial compartmental joint line elevation and FTA correction
      after UKA, and the proximal tibial osteotomy was critical during the procedure.
      There was no significant correlation between joint line elevation and the
      clinical function, which may be related to the design of UKA prosthesis.

PMID- 29349979
TI  - [Capsular-enhanced repair with suture anchors in bipolar hemiarthroplasty for the
      treatment of femoral neck fractures in elderly patients].
AB  - OBJECTIVE: To evaluate the efficacy of capsular-enhanced repair with suture
      anchors in bipolar hemiarthroplasty for the treatment of femoral neck fractures
      in elderly patients. METHODS: A retrospective study was designed. From June 2009
      to June 2016, 53 senile patients (54 hips)with femoral neck fracture were treated
      operatively in Mianyang central hospital (Sichuan, China). There were 21 males
      and 32 females, ranging in age from 80 to 97.5 years old (mean, 84.7 years old).
      There were 11 hips of Garden type II, 26 hips of Garden type III and 17 hips of
      Garden type IV. All the patients underwent bipolar hemiarthroplasty with enhanced
      repair of hip capsular. The hip joint was opened by a T shaped incision over
      posterior capsule. The posterior hip capsular and short external rotators were
      repaired particularly after the bipolar prostheses were implanted. Surgical time,
      intra-operative blood loss, mean hospitalization time, deep venous thrombosis,
      mortality, hip dislocation, pain, periprosthetic fracture, and other
      complications were recorded. The functional outcome was evaluated using the
      Harris Hip Score at the last follow-up. RESULTS: The 53 patients (54 hips) were
      evaluated during the hospitalization period and a mean follow-up period of 11.5
      months(ranged, 3 to 36 months). No dislocation, incision infection and
      periprosthetic fracture appeared in this group. The mean surgical time was 65
      minutes(ranged, 50 to 95 min). The mean intra-operative blood loss was 213
      ml(ranged, 100 to 420 ml) and the mean hospitalization time was 13.3 days(ranged,
      5 to 27 days). Two patients with deep vein thrombosis, one patient with pulmonary
      embolism and 10 patients with venous plexus thrombosis of calf muscle were
      diagnosed postoperatively. The rate of venous thrombosis was 24.53% (13/53). The
      patient with pulmonary embolism died 8 days after operation and the other 3
      patients died from heart failure 4, 6 and 7 months after operation respectively.
      The mortality during first year after hemiarthroplasty was 7.55% (4/53). At the
      latest follow-up, 42 patients (43 hips)had no pain, 9 patients had mild pain, and
      2 patients had moderate pain. No patients were non-ambulatory. The mean Harris
      Hip Score was 91.25+/-8.39, functional outcome was excellent in 44 hips, good in
      5, and fair in 5. CONCLUSIONS: The bipolar hemiarthroplasty with capsular
      enhanced repair with suture anchors is effective in reducing postoperative
      complications of prosthesis dislocation.

PMID- 29349980
TI  - [Clinical analysis on arthroscopic debridement for the treatment of early
      infection after total knee replacement].
AB  - OBJECTIVE: To compare the clinical effects of arthroscopic debridement versus
      open debridement on controlling and treatment of infection after total knee
      replacement. METHODS: From October 2009 to September 2016 in three hospitals, 11
      patients with 11 joints which were infected after total knee replacement were
      randomly divided into two groups:5 cases in arthroscopy group and 6 cases in
      routine group. Patients in arthroscopy group were treated with arthroscopic
      debridement to remove the necrotic tissues, then closed-type irrigation with
      sensitive antibiotics by using two sebific ducts were performed continuously for
      2 or 3 weeks until the flushing fluid became clear for 3 or 5 days;other 6
      patients in routine group were treated with open surgical debridement and the
      following procedures in keeping with those in the arthroscopy group. Operation
      time, blood loss and incision length were recorded during the operation, and pain
      scores were recorded on the 1st, 3rd and 7th day after the operation. The
      curative effects were evaluated according to the Hospital for Special Surgery
      score system. RESULTS: The local and general symptoms of the 11 patients
      disappeared, and the test outcomes of biochemistry, blood and synovial fluid were
      normal. All patients were followed up, and the duration ranged from 6 to 18
      months. Infection recurrences were observed in 1 case of arthroscopy group and 2
      cases of routine group 3 months later after operation, and all these patients who
      underwent the second time operation with arthroscopic debridement were cured.
      According to the Hospital for Special Surgery score system, 3 cases obtained
      excellent result, 2 good, no poor and bad cases in arthroscopy group;3 cases
      obtained excellent result, 1 good, 1 poor and 1 bad in routine group.
      CONCLUSIONS: If the sensitive antibiotics can be found for the infected joints
      without obvious destruction of bone and no prosthesis loosening, it has a better
      therapeutic effect by using arthroscopic debridement combined with continuous
      drainage and irrigation. The method has a better curative effect with smaller
      trauma.

PMID- 29349981
TI  - [Clinical results in early and mid term of using the S-ROM femoral stem in
      revision].
AB  - OBJECTIVE: To investigate and the clinical effect of S-ROM modular stem in femur
      reconstruction in hip revision arthroplasty. METHODS: From January 2008 to
      January 2016, 21 patients received revision hip arthroplasties using S-ROM stems.
      There were 5 males and 16 females with an average of 48.33 years old(range, 29 to
      73 years old). There were 13 cases caused by aseptic loosening, 4 cases by
      infection, 2 cases by nonunion of sub-tuberosity osteotomy, 1 case for repeated
      dislocation, 1 case for traumatic great trochanter fracture. Primary THA
      reasons:12 cases for DDH(9 cases for Crowe IV), 5 cases for femoral neck
      fracture, 2 cases for necrosis of femoral head, 2 cases for proximal femoral
      deformity caused by early infection. The femur bone defects included Paprosky II
      in 11 cases, IIIa in 9, and IIIb in 1. Harris hip score , pain score and hip
      flexion were recorded before and after operation. The subjective satisfaction was
      recorded at the last follow-up. RESULTS: The operation time and blood loss were
      189 min(125 to 290 min) and 867 ml (200 to 2 000 ml). At the final followup, the
      pain score improved from (17.14+/-9.56) points preoperatively to (41.71+/-2.03)
      points (t=11.42, P=0.00). The function score improved from (24.01+/-11.02) points
      preoperatively to (49.95+/-5.38) points (t=9.73, P=0.00). Harris hip score
      improved from (41.15+/-14.81) points preoperatively to(91.67+/-5.83)
      points(t=15.33, P=0.00). The degree of hip flexion increased from (93.10+/-27.27)
      points preoperatively to (121.90+/-16.62) points at the last follow-up (t=4.59,
      P=0.00). The mean subjective satisfaction was 9.48(10 points system), 14 of which
      were completely satisfactory. The last follow-up hip X-ray showed 21 cases of
      bone ingrowth, and other femoral stem without loosening or sinking sign
      significantly. There were 5 cases with bone anchor syndrome around proximal
      femoral cuff. There were 5 cases of proximal femur fracture, 3 cases of lesser
      trochanter fracture, 2 cases of greater trochanter fracture intra-operatively.
      Due to femoral canal stenosis, there were 4 cases of pre-tied wire at lesser
      trochanter to prevent fractures. There was 1 case of traumatic femoral fracture
      around stems with a distal oblique fracture, open reduction and locking plate
      fixation was performed. Other patients had no nerve stretch injury, dislocation,
      infection and lower limb deep vein thrombosis and other complications at the
      final follow-up. CONCLUSIONS: S-ROM prosthesis has satisfactory results in hip
      revision arthroplasty with Paprosky II and III femoral defects. Especially for
      patients with Crowe IV DDH and other proximal femoral deformities, it is possible
      to adapt to the medullary cavity morphology. Excellent initial stability, less
      complications and long-term biological fixation can be achieved with S-ROM in
      femur revision.

PMID- 29349982
TI  - [Effects of tranexamic acid combined with temporary drain clamping on
      postoperative blood loss in total knee arthroplasty].
AB  - OBJECTIVE: To evaluate the efficacy and safety of one dose tranexamic acid
      combined with temporary drain lamping in primary unilateral total knee
      arthroplasty. METHODS: Total 160 patients undergoing unilateral primary total
      knee arthroplasty between January 2012 and December 2013 were randomly divided
      into four groups(40 cases in each group):group A (the drain was clamped for 2
      hours after the operation and the patients received 20 ml physiological saline),
      group B(the drain was clamped for 2 hours after the operation and the patients
      received 10 ml tranexamic acid and 10 ml physiological saline), group C (the
      drain was clamped for 4 hours after the operation and the patients received 20 ml
      physiological saline) and group D(the drain was clamped for 4 hours after the
      operation and the patients received 10 ml tranexamic acid and 10 ml physiological
      saline). The postoperative hemoglobin level, maximum hemoglobin loss, wound
      drainage, blood loss, the volume of blood transfusion, the number of patients
      inquiring blood transfusion, venous thrombo embolism rate, and ecchymosis rate
      were recorded and compared among the four groups. RESULTS: There was no incision
      infection, severe hypoxia, and symptomatic pulmonary embolism in these groups.
      There were significant differences in hemoglobin content one day after operation
      in each group(F=12.26, P=0.000), in the hemoglobin content 7 days after operation
      in each group(F=20.74, P=0.000), in postoperative drainage in each group(F=38.71,
      P=0.000);in the amount of invisible red blood cell loss in each group(F=83.41,
      P=0.000), and in total red blood cell loss in each group(F=102.68, P=0.000).
      Color Doppler ultrasound examination found that the total incidence of VTE was
      3%(5/160) and there were no significant differences in each group(P=0.892). There
      were no significant differences in postoperative subcutaneous ecchymosis area>1%
      incidence(P=0.143). CONCLUSIONS: Topical tranexami acid treatment combined with
      temporary clamping of drain for 4 hours could reduce postoperative blood loss,
      blood transfusion, and ecchymosis rate without increasing the risk of
      thromboembolic event after total knee arthroplasty.

PMID- 29349983
TI  - [Treatment of posterior cruciate ligament avulsion fracture with rivet-assisted
      hollow nail:a case-control study].
AB  - OBJECTIVE: To retrospectively investigate the clinical effect of the rivet
      assisted hollow screw in the treatment of posterior cruciate ligament avulsion
      fracture. METHODS: Total 49 patients with knee cruciate ligament avulsion
      fracture in the ending point of the ligament from January 2010 to December 2014
      were divided into the treatment group and the control group. Thirty-one patients
      in treatment group were treated with rivet-assisted double cannulate nail,
      including 13 males and 18 females, ranging in age from 38 to 51 years old, with a
      mean of (40.6+/-5.1) years old; according to Meyers classification, 23 cases of
      type 2, 8 cases of type 3; 5 patients were caused by the low energy injury and 26
      patients were caused by the high energy injury. Eighteen patients in control
      group were treated with double gold hollow screw fixation, including 5 males and
      13 females, ranging in age from 36 to 52 years old, with an average age of
      (4.16+/-4.7) years old; according to Meyers classification, 14 cases of type 2
      and 4 cases of type 3;2 patients were caused by the low energy injury and 16
      patients were caused by the high energy injury. The operation time, postoperative
      complications, fracture healing time and the last AKS scoring system were
      compared between the two groups. RESULTS: All the patients were followed up, and
      the duration ranged from 12 to 24 months, with an average of 14.2 months. The
      patients in treatment group had no displacement of fracture fragments and
      internal fixation failure. The results of AKS score:pain was 48.1+/-1.5, activity
      was 21.3+/-2.7, stability was 20.9+/-2.5, walking ability was 47.3+/-1.9, under
      the stairs ability was 43.4+/-2.1, the total score was 190.7+/-2.9. There were 2
      cases in control group had fracture fragment displacement and 1 patient had nail
      withdraw. The results of AKS score:pain was 40.1+/-2.2, activity was 20.1+/-0.2,
      stability was 18.1+/-3.2, walking ability was 46.3+/-1.7, under the stairs
      ability was 40.2 +/-1.3, the total score was 180.2+/-1.4. Therefore, the
      comparison of the above indicators, the results of the treatment group were
      better than those of the control group. CONCLUSIONS: Rivet-assisted hollow screw
      fixation in the treatment of cruciate ligament avulsion fracture in the ending,
      has some advantages such as follows:accurate reduction, less postoperative
      complications and better postoperative knee function recovery, therefore it is an
      effective way to treat posterior cruciate ligament avulsion fracture.

PMID- 29349984
TI  - [Risk factors analysis on wound complications after closed calcaneal frature
      operation using lateral extensive L-shaped incision].
AB  - OBJECTIVE: To investigate the risk factors of wound complications after closed
      calcaneal fracture operation using a lateral extensive L-shaped incision and to
      explore the effective interventions to reduce the complications after incision.
      METHODS: Retrospective analysis of clinical data of 285 patients(315 calcaneal
      fractures) who underwent open reduction and internal fixation by using the
      lateral extensive L-shaped incision from January 2011 to January 2015. Eighteen
      factors which might cause the complications of calcaneal incision were compared
      by univariate analysis, and multiple Logistic regression analysis was performed
      for factors with statistically significances. RESULTS: Twenty-nine patients(30
      calcaneus) had wound complications among all the 285 patients(315 calcaneus)
      after surgery, including 9 patients with incision redness, swelling, oozing or
      nonunion;16 patients with skin necrosis or incision rupture, 3 patients with soft
      tissue superficial infection, and 2 patients with osteomyelitis. Univariate
      analysis showed that fall height(P=0.017), diabetes (P=0.026), smoking(P=0.001),
      and operative time(P=0.003) were correlated with incision complications after
      surgery. Multivariate analysis showed that diabetes(P=0.029), smoking(P<0.001),
      and operative time(P=0.018) were risk factors for incision complications after
      operation. CONCLUSIONS: Preoperative smoking cessation, actively control of blood
      glucose and shortening the operation time by practicing can effectively reduce
      the incision complication after fracture surgery with the lateral extensive L
      shaped incision.

PMID- 29349985
TI  - [Risk factors analysis for low back pain in patients with multiple sclerosis].
AB  - OBJECTIVE: To investigate musculoskeletal disorders and risk factors of low back
      pain in multiple sclerosis (MS) patients. METHODS: In this study, patients in our
      hospital with confirmed MS with an expanded disabilitystatus scale (EDSS) score
      between 4 to 7 were selected. Data of MS history, pain, musculoskeletal
      disorders, muscle strength and spasticity in lower limbs were collected. RESULTS:
      Among 190 patients, there were 61 males and 129 females, with an average age
      of(54.9+/-9.2) years old. The mean disease duration was(19.3+/-9.9) years, and
      the median EDSS score was 6. Forty-two patients were relapsing-remitting type, 45
      patients were primary progressive type, and 93 patients were secondary
      progressive type. The most common musculoskeletal disorders were described as
      follows:knee osteoarthritis (15 cases), claw toe (13 cases) and genu recurvatum
      (12 cases). Seventy-nine patients with prevalence low back pain was higher than
      in patients with a progressive type(secondary: OR=2.958, P=0.007 9,
      primary(OR=2.629, P=0.039 8) and in patients who had a visual dysfunction at EDSS
      score(OR=1.411, P=0.012 4). The prevalence was reduced in male patients(OR=0.306,
      P=0.001 4). CONCLUSIONS: The progressive type of MS and visual dysfunction
      increased the risk of low back pain in these patients.

PMID- 29349986
TI  - [Observation of curative effects of musculoskeletal ultrasound-guided needle
      knife on the degenerative meniscus disease].
AB  - OBJECTIVE: To observe the curative effect of musculoskeletal ultrasound-guided
      needle-knife on the degenerative meniscus disease, and to provide a new method in
      the treatment of degenerative meniscus disease. METHODS: Seventy-seven patients
      with degenerative meniscus disease treated in the Third Affiliated Hospital of
      Beijing University of Chinese Medicine from January 2015 to September 2015 were
      selected, including 30 males and 47 females, aged from 44 to 66 years old, with
      an average of 57.5 years old. VAS scores, Lysholm scores and distance of meniscal
      protrusion were analyzed and compared before treatment, 2 weeks and 1 month after
      treatment. The curative effect was summarized at last. RESULTS: The mean Lysholm
      scores were 51.63+/-15.26(before treatment), 77.13+/-11.82(2 weeks after
      treatment) and 87.56+/-8.65(1 month after treatment). The mean VAS scores were
      7.080+/-1.574 (before treatment), 2.630+/-0.310(2 weeks after treatment) and
      0.850+/-0.177(1 month after treatment). The mean of the distance of meniscal
      protrusion scores were 0.400+/-0.156 (before treatment), 0.298+/-0.140 (2 weeks
      after treatment) and 0.240+/-0.110 (1 month after treatment). VAS scores and
      Lysholm scores were improved significantly compared with preoperative results.
      The distance of meniscal protrusion showed an obvious improvement after
      treatment. CONCLUSIONS: The treatment of musculoskeletal ultrasound-guided needle
      knife has advantages of high accuracy position and excellent effectiveness for
      degenerative meniscus disease. The treatment provides safety operation and
      significantly improves quality of life in patients without any complications.

PMID- 29349987
TI  - [CT measurement and clinical application of double-row suture anchor
      reconstruction for the treatment of Tossy type III acromioclavicular joint
      dislocation].
AB  - OBJECTIVE: To study feasibility and reliability of reconstruction of the
      acromioclavicular ligament with double-row suture anchor for the treatment of
      acromioclavicular joint dislocation through coracoid coronal CT measurement, and
      to provide a new operation method for treating acromioclavicular joint
      dislocation. METHODS: Total 60 healthy people received CT examination of shoulder
      joint, including 30 males and 30 females, ranging in age from 18 to 50 years old.
      The coronal width, thickness and 20 degree camber angle in the medial part of the
      toot of coronal were measured using CT scan. The results were applied to clinical
      treatment for 12 patients with acromioclavicular joint dislocation of Tossy III
      type. RESULTS: The width in the medial part of the root of the coracoid
      was(17.65+/-1.82) mm(left side) and (17.67+/-1.80) mm(right side) in males;
      (16.55+/-1.78) mm(left side) and (16.52+/-1.74) mm (right side) in females. The
      vertical thickness of the roots of the coracoid: (13.11+/-2.11) mm(left side) and
      (13.16+/-2.09) mm(right side) in males;(12.79+/-2.21) mm(left side) and (12.76+/
      2.19) mm (right side) in females. The thickness of 20 degrees camber angle of the
      coracoid roots: (16.32+/-1.74) mm (left side) and (16.30+/-1.69) mm(right side)
      in males; (15.68+/-1.44) mm(left side) and (15.67+/-1.43) mm(right side) in
      females. Total 12 patients were treated with anchor nail with extraversion 20
      degrees. The postoperative X-ray films showed bone anchors were located in the
      coracoid process, no bone splitting. CONCLUSIONS: Double-row suture anchor of 5
      mm diameter nails can be placed into coracoid with extraversion 20 degrees, which
      is safety.

PMID- 29349988
TI  - [Comparison of analgesic effects between multimodal and patient-controlled
      intravenous analgesia in patients with rheumatoid arthritis in the perioperative
      period of total knee arthroplasty].
AB  - OBJECTIVE: To compare the analgesic effect between multimodal and patient
      controlled intravenous analgesia(PCIA) in patients with rheumatoid arthritis(RA)
      in the perioperative period of knee joint replacement. METHODS: From June 2015 to
      June 2016, 40 RA patients undergoing total knee arthroplasty were randomly
      divided into two groups. There were 20 patients in PCIA group, including 3 males
      and 17 females, with an average age of(59.6+/-2.3) years old, who received
      controlled instillation of sufentanil analgesia controlled by an intravenous
      analgesia pump. There were 20 patients in multiple model analgesia group,
      including 2 males and 18 females, with an average age of(56.3+/-1.3) years old,
      who were treated with continuous femoral nerve block, local injection of knee
      joint and combined buprenorphine patches. The VAS score and the incidence of
      adverse reactions and HSS score were compared between the two groups after
      operation. The advantages and disadvantages of the two modes of analgesia were
      evaluated. RESULTS: On the 6 th and 24 th hours after surgery, the VAS scores of
      the multimodal analgesia group were significantly lower than those of the PCIA
      group(P<0.01). On the 48 th hour after surgery, the VAS scores was significantly
      lower in the multimodal analgesia group than those in PCIA group(P<0.000 1), both
      in the state of motion and at rest. On the 1 st week after surgery, the HSS score
      of the multimodal analgesia group was significantly higher than that in the PCIA
      group(P<0.000 1). The pain score and the degree of activity in HSS score of the
      multimodal analgesia group were better than those in PCIA group (P<0.05). The
      functional score of multimodal analgesia group was significantly better than that
      of PCIA group(P<0.01). But there was no significant difference in muscle strength
      scores between two groups. CONCLUSIONS: Multimodal analgesia is an ideal
      analgesic plan for total knee arthroplasty TKA patients with RA in perioperative
      period, which has good effects and little adverse reaction.

PMID- 29349989
TI  - [Artificial radial head replacement for the treatment of comminuted fractures of
      the radial head].
AB  - OBJECTIVE: To assess the clinical effects of artificial radial head prosthesis
      replacement for the treatment of comminuted fracture of the radial head. METHODS:
      From June 2011 to June 2015, 25 patients with radial head comminuted fracture
      were treated with artificial radial head replacement, including 10 males and 15
      females, ranging in age form 24 to 61 years old(mean, 40 years old). The
      functional recovery of the patients suffering from limb and elbow in different
      periods, the activity degree of the elbow joint and the function of the elbow in
      the latest follow-up were compared. RESULTS: All the patients were followed up,
      and the duration ranged from 12 to 48 months, averaged 26 months. There were no
      complications such as infection, elbow instability, subluxation of the distal
      radioulnar joint, and myositis ossificans. The VAS, Broberg and Morrey elbow
      function score were improved 6, 9 months after operation compared with that 3
      months after operation(P<0.05). There were significant differences in elbow
      flexion and extension, rotation activity between injured side and healthy side 3,
      6, 9 months after operation(P<0.01), but no significant differences between
      injured side and healthy side at the latest follow-up(P>0.05). At the latest
      follow-up, according to Broberg and Morrey elbow function evaluation criteria, 16
      cases got an excellent result, 7 good and 2 poor. CONCLUSIONS: It can maximize
      the recovery of elbow joint stability and quicken early functional exercise,
      prevent and reduce the occurrence of complications by using the artificial radial
      head replacement therapy to repair comminuted fracture of the radial head. The
      short-term curative effect is satisfactory, but the long-term effect needs
      further observation.

PMID- 29349990
TI  - [Experimentation of the relationship between medial or lateral patellar
      stabilizer and patellofemoral stabilization].
AB  - OBJECTIVE: To study the contribution of medial or lateral stabilizer to the
      stability of the patella, to explore the function and effect of releasing the LPR
      clinically and to provide a biomechanical basis for the clinical treatment of
      patellar instability(PI). METHODS: The quadriceps femoris of 6 fresh human
      cadaver knees were loaded to simulate a normal condition of muscle strength.
      First the loading force was measured and recorded, which subluxated the patella
      with the different degrees of knee flexion. Intervention 1:released the medial
      patellar retinaculum(MPR) to simulate pathologic conditions, then repeated the
      above manipulates and recorded the loading force. Intervention 2:released the LPR
      furthermore to simulate clinical surgical treatment, then repeated the above
      manipulates and recorded the loading force. RESULTS: After releasing the MPR, the
      loading force which subluxated the patella were decreased obviously, and there
      were significant differences between the two groups(P<0.05). The above loading
      force was further decreased after the further release of LPR, but the difference
      was not significant(P>0.05). CONCLUSIONS: MPR plays an important role in
      maintaining the stability of the patella and in the normal trajectory of the
      patellofemoral joint. The attention should be paid to the repair or
      reconstruction of the MPR in the treatment for patella recurrent lateral
      dislocation subluxation. Releasing the LPR is not a best choice.

PMID- 29349991
TI  - [Effects of creating a tunnel through intercondylar fossa under arthroscopy for
      the treatment of complex tears at the medial meniscus posterior horn].
AB  - OBJECTIVE: To discuss the advantages of the arthroscopic treatment for complex
      tears of the medial meniscus posterior horn by creating a tunnel passageway
      through the intercondylar fossa. METHODS: All 127 patients including 24 males and
      103 females with complex tears at the medial meniscus posterior horn were
      reviewed. The age of all patients ranged from 45 to 78 years old, with an average
      of 67 years old. All 127 patients were treated with partial meniscectomy, in
      which 112 patients were treated with partial meniscectomy smoothly with three
      incisions (anterior medial incision, anterior lateral incision, high anterior
      lateral incision), and 15 patients were treated with four incisions (anterior
      medial incision, anterior lateral incision, high anterior lateral incision,
      posterior medial incision). Four aspects were estimated:whether the meniscus
      posterior horns could be observed totally and conveniently, whether tools could
      be pushed to target area conveniently, the damage of adjacent cartilages,
      operation time(the operation time of partial meniscectomy). RESULTS: Posterior
      horns of all patients were totally and conveniently observed, tools were
      conveniently pushed to the target area in all cases, and all the cases had no
      iatrogenic injuries at adjacent cartilages. The operation time of partial
      meniscectomy at posterior horns with three incisions ranged from 5 to 10 minutes,
      and it ranged from 10 to 30 minutes with four incisions. CONCLUSIONS: It is very
      convenient and fast of the arthroscopy to treat complex tears of the medial
      meniscus posterior horn by creating a tunnel through the intercondylor fossa.
      Iatrogenic injuries of the adjacent cartilages were prevented to the greatest
      extent.

PMID- 29349992
TI  - [Excision of necrotic and infected tissues combined with induced membrane and
      external fixator technique for the treatment of chronic osteomyelitis in tibia
      after fracture operation].
AB  - OBJECTIVE: To investigate the clinical efficacy of excision of necrotic and
      infected tissues combined with induced membrane and external fixator technique to
      treat chronic osteomyelitis in tibia after fracture operation. METHODS: From June
      2011 to June 2014, a total of 13 patients with tibia osteomyelitis were treated
      with excision of necrotic and infected tissues and external fixator technique in
      the first stage. There were 8 males and 5 females, ranging in age from 16 to 67
      years old with an average of (37.3+/-14.3) years old. Within 6 to 8 weeks the
      induced membrane was formed and the induced membrane technique was applied to
      promote new bone forming in the second stage. RESULTS: Thirteen patients had no
      reinfection and achieved complete bone healing after 24 to 52 months follow-up.
      All the patients had satisfactory function. CONCLUSIONS: Excision of necrotic and
      infected tissues combined with induced membrane and external fixator technique to
      treat chronic osteomyelitis in tibia after fracture operation can provide
      satisfactory results.

PMID- 29349993
TI  - [Accurate osteotomy assisted by individualized navigation templates for the
      treatment of children cubitus varus].
AB  - OBJECTIVE: To investigate the feasibility and accuracy of a new navigation
      template for osteotomy in cubitus varus based on computer assistant design and 3D
      printing technology. METHODS: The preoperative CT images of 15 children with
      cubitus varus from June 2015 to June 2016 were collected. According to the above
      data, the individual osteotomy navigate template match the distal humerus was
      designed by the software and printed by the 3D printer. Accurate osteotomy was
      performed with the assistant of the navigate template in the operation. Internal
      fixation of the osteotomy site was performed with 2 Kirschner wires. After
      surgery, a long arm plaster was applied with 20 degrees  of elbow flexion. All
      the patients underwent radiographic and clinical evaluations before surgery and
      at the follow-up examination. RESULTS: During the operation, the navigate
      template with the individual design of 3D printing technology matched the bony
      markers of distal humerus. Accurate and simple osteotomy were performed along the
      resected surface of the navigation template. None of the cases required any kinds
      of revision surgery or had any complaint of cosmetic appearance. Average union
      time was 6.7 weeks(ranged, 6 to 8 weeks). Twelve patients got an excellent result
      and 2 got a good result according to the criteria described by Bellemore. There
      were no cases with complications of infection or ulnar nerve palsy or joint
      stiffness. CONCLUSIONS: With the help of 3D printing technology, the accurate
      osteotomy in cubitus varus assisted by individualized navigate template can be
      realized. This technology can restore normal anatomical structure of the elbow
      joint to the greatest extent. It is worthy of popularization and application.

PMID- 29349994
TI  - [Double hip and knee joint replacement for the treatment of rheumatoid arthritis
      with severe osteoporosis:a case report].

PMID- 29349995
TI  - [Progress on graft and fixation options of arthroscopic anterior cruciate
      ligament reconstruction].
AB  - Anterior cruciate ligament injury is one of the most common injuries of knee
      joint. Arthroscopic reconstruction of anterior cruciate ligament is the most
      commonly performed procedure. A variety type of fixation techniques are being
      used nowadays, such as interference screw, cortical suspension fixation and
      transfix, all of which can achieve good effect, with both advantages and
      disadvantages. However, the healing of reconstructed grafts is a complicated and
      long-term process, which can be affected by many factors. The mechanical
      properties of the grafts are also changed greatly in all stages of healing
      process, adding variables for the post-operative rehabilitation.

PMID- 29349996
TI  - [To implement minimally invasive endoscopic spinal surgery proactively and safely
      by mastering multiple techniques].

PMID- 29349997
TI  - [Surgical outcome of percutaneous endoscopic technique for highly migrated disc
      herniation via three different approaches].
AB  - OBJECTIVE: To analyze the clinical effects of percutaneous endoscopic technique
      via three different approaches for highly migrated lumbar disc herniation.
      METHODS: The clinical data of 68 patients underwent percutaneous endoscopic
      technique from June 2011 to June 2014 were retrospectively analyzed. There were
      43 males and 25 females, aged from 11 to 77 years old with an average of (42.29+/
      15.92) years. The patients were divided into three groups according to different
      operative approaches, of them, 45 cases were by transforaminal approach (group
      A), 15 cases by translaminar approach (group B), and 8 cases by transpedicular
      approach (group C). There was 1 case in level L2,3, 12 cases in L3,4, 36 cases in
      L4,5, 19 cases in L5S1. The herniated disc was migrated superiorly in 23
      patients, inferiorly in 45 patients. MRI were available to confirm migrated disc
      pre-and post-operatively. Operation time, loss blood volume, intraoperative and
      postoperative complications, time of back to work (postoperative recovery time)
      were recorded. Preoperative and postoperative VAS were used to evaluate low back
      pain and sciatica and JOA and MacNab criteria were used to evaluate functional
      recovery. RESULTS: All the operations were successful and all the patients were
      followed up from 12 to 40 months with an average of (18.0+/-15.9) months. Seven
      patients(3 cases in group A, 3 cases in group B, 1 case in group C) complicated
      with transient paraesthesia (hyperalgesia or hypesthesia), and the symptoms
      relieved after symptomatic treatment with neurotrophic medicine, at final follow
      up, no symptoms were left. One case in group B complicated with dura mater
      tearing during operation and it was untreated, there was no resulted
      complications such as headache and sinus tract of skin. In group A, B, C, the
      mean VAS score of sciatica improved from preoperative 6.93+/-1.34, 6.33+/-1.23,
      6.13+/-1.73 to 0.80+/-0.87, 0.73+/-0.70, 0.38+/-0.52 at final follow-up; and JOA
      score improved from preoperative 9.09+/-2.62, 9.80+/-2.31, 10.50+/-2.93 to
      26.82+/-1.53, 25.93+/-1.58, 26.50+/-1.51 at final follow-up,
      respectively(P<0.05). There was no significant difference among three
      groups(P>0.05). There was no significant difference in loss blood volume,
      postoperative recovery time among three groups. But operation time of group B was
      shorter than other two groups. According to MacNab criterion to assess the
      clinical effects, 42 cases got excellent results, 21 good, 5 fair. CONCLUSIONS:
      Percutaneous endoscopic technique is a safe and effective method for surgical
      treatment of highly migrated herniation. The decision of operative approach
      should be made by characters of anatomy. By tanspedicular approach the lesion
      could be found directly. However, it depends on good skill and equipment.

PMID- 29349998
TI  - [Comparative study of minimally invasive percutaneous pedicle screw fixation and
      open surgery in the treatment of thoracolumbar fractures].
AB  - OBJECTIVE: To compare the clinical outcomes of minimally invasive percutaneous
      pedicle screw fixation and open surgery in the treatment of thoracolumbar
      fracture. METHODS: A retrospective study of patients who had undergone surgery
      for thoracolumbar fracture from June 2014 to December 2014 was performed. Sixty
      one cases were included and 29 cases were treated by minimally invasive
      percutaneous pedicle screw fixation (minimally invasive group) and 32 cases were
      treated by the traditional open pedicle screw fixation(open group). The
      differences in the total length of the incision, intraoperative fluoroscopy
      times, operative time, blood loss, the preoperative and postoperative visual
      analogue scale(VAS), postoperative bedridden time and hospital stay were
      compared. And the preoperative and postoperative anterior vertebral body height
      and Cobb angle of the kyphosis were also compared. RESULTS: Compared with the
      open group, the total length of incision was smaller and intraoperative blood
      loss was less, bedridden time and hospital stay were shorter, and pain of the
      wound was less in the minimally invasive group. Postoperatively, the anterior
      vertebral body height was retorted and the Cobb angle of the kyphosis was
      corrected obviously in both groups. But no significant difference in the imaging
      results was found between two groups(P>0.05). CONCLUSIONS: Minimally invasive
      percutaneous pedicle screw fixation has the similar fixation efficacy with open
      surgery in treating thoracolumbar fracture. However, it can avoid extensive
      muscle stripping, and obviously reduce the surgical incision, operative time,
      postoperative pain, bedridden time and hospital stay. According to the clinical
      efficacy, it is worthy of clinical application.

PMID- 29349999
TI  - [Percutaneous endoscopic lumbar discectomy combined with epidural injection for
      prolapsed lumbar disc herniation].
AB  - OBJECTIVE: To assess the effect of percutaneous endoscopic lumbar discectomy
      (PELD) combined with epidural injection for prolapsed lumbar disc
      herniation(PLDH). METHODS: In this prospective randomized controlled study, the
      clinical data of 126 patients who had undergone a PELD because of a single-level
      PLDH from March 2014 to June 2015 were analyzed. There were 67 males and 59
      females, ranging in age from 17 to 75 years old with an average of(41.0+/-13.5)
      years old, 9 cases were L3,4, 76 cases were L4,5 and 41 cases were L5S1.
      According to the random number table, the patients were randomized into two
      groups, with 63 patients in each group. Patients in group 1 were injected normal
      saline after PLED, patients in group 2 were subjected to an epidural injection of
      Diprospan, Lidocaine and Mecobalamine after PLED. All the patients were followed
      up from 6 to 20 months with the mean of 12.4 months. Complications, the
      postoperative hospital stay, the period of return to work, visual analogue scale
      (VAS) and Japanese Orthopedic Association (JOA) score were compared between two
      groups, and clinical outcomes were evaluated according to modified MacNab
      criteria. RESULTS: All the operations were successful, and no complications were
      found. The mean postoperative hospital stay and the period of return to work in
      group 1 were (4.61+/-1.25) days and (4.31+/-0.47) weeks, respectively, and in
      group 2 were (2.53+/-0.69) days and (3.14+/-0.52) weeks, there was significant
      differences between two groups(P=0.000). Postoperative VAS and JOA scores in two
      groups were obviously improved (P=0.000). At 1 day, 1 week, 1 month after
      operation, VAS, JOA scores in group 2 were better than that of group 1(P=0.000),
      and after 6 months, there was no significant difference between two
      groups(P>0.05). According to the modified MacNab criteria, 39 cases got excellent
      results, 21 good, 3 fair in group 1, and which in group 2 were 41, 20, 2,
      respectively, there was no significant difference between two groups(P=0.087).
      CONCLUSIONS: PELD is an mini-invasive technique for PLDH, it can fleetly reduce
      pain and improve function. And combination with epidural injection has the
      advantages of pain releasing and function improving in the short-term
      postoperative period, and it can decrease postoperative hospital stay and time of
      returning to work, and it is a safe and effective method.

PMID- 29350000
TI  - [Percutaneous vertebroplasty and open vertebroplasty for metastatic spinal
      tumor].
AB  - OBJECTIVE: To explore the clinical application and therapeutic effect of
      percutaneous vertebroplasty(PVP) and open vertebroplasty for metastatic spinal
      tumor. METHODS: The clinical data of 126 patients with metastatic spinal tumor
      underwent surgery and obtained follow-up from January 2012 to March 2016 were
      retrospectively analyzed. These 126 cases were divided into two groups according
      to different operative methods. The metastatic tumor of 43 cases encroached
      vertebral canal oppressing spinal cord and nerve root, they were treated with
      open operation(open vertebroplasty group);and other 83 cases without obviously
      spinal cord or nerve root compression, or unfit for open operation, were treated
      with PVP (percutaneous vertebroplasty group) . VAS score, ECOG and Frankel grade
      were used to evaluate the pain and neurofunction in two groups.All out-hospital
      patients were followed up every 3 months for 1 time. X-ray, CT, MRI were examined
      in follow-up. RESULTS: A total of 112 vertebrae underwent PVP with the median
      surgical time of 50 min;VAS scores decreased significantly at 2 days after
      operation, which maintained till 1 month later; ECOG grade at 1 month decreased
      significantly;44 of 112 vertebrae suffered from asymptomatic bone cement leakage,
      no complications such as nerve injury or pulmonary embolism was found; the median
      survival time was 16 months. While for open vertebroplasty group, the median
      surgical time was 160 min and blood loss was 1 000 ml; postoperative VAS scores
      and ECOG grade at 1 month decreased significantly. Postoperative Frankel grade of
      36 patients got improvement in 41 patients with spinal cord functional
      disturbance(87.8%); and 29 of 40 patients with incompleteness out of motor
      function were full recovery(76.3%); 12 cases (27.9%) occurred complications and
      the median survival time was 11 months. CONCLUSIONS: The different vertebroplasty
      treatments can be selected for patients with metastatic spinal tumor, which can
      relieve the pain, improve the nerve function, reconstruct the spinal
      stabilization, maintain the local control and raise the life quality.

PMID- 29350001
TI  - [Analysis of complications of percutaneous endoscopic lumbar discectomy].
AB  - OBJECTIVE: To analyze the complications of lumbar intervertebral disc herniation
      treated with percutaneous endoscopic lumbar discectomy(PELD), and discuss how to
      avoid these complications. METHODS: The data of 132 patients with lumbar
      intervertebral disc herniation underwent PELD from October 2013 and June 2015
      were retrospectively analyzed, including 85 males and 47 females with an average
      age of 42.9 years old. There were 6 cases of L3,4, 68 of L4,5 and 58 of L5S1. The
      incidences of intraoperative and postoperative complications were analyzed.
      RESULTS: There was spinal dura mater injury in 1 patient, but no cerebrospinal
      fluid leakage and nerve function deficit was found, the muscle strength did not
      decrease postoperatively and the incision healed well. Two patients converted to
      open surgery ultimately because of stenosis of the intervertebral foramen and
      adhesion between nucleus pulposus and spinal dura mater; two patients complicated
      with early recurrence(in 3 months);nucleus pulposus residue developed in 3
      patients; all of them were treated by open surgery and got satisfactory results.
      One patient with heart disease history complicated with supraventricular
      tachycardia after surgery and 2 patients with the increased cerebrospinal fluid
      pressure during surgery. CONCLUSIONS: PELD have a steep learning curve, and the
      technology is a safe and effective method in treating lumbar disc herniation, but
      the beginners must have enough open surgery experience, and to grasp indications
      strictly.

PMID- 29350002
TI  - [Progress on laminoplasty in spinal canal disease].
AB  - Surgery is the preferred method for the treatment of spinal canal disease,
      surgical method involves laminectomy and laminoplasty. The ideal spinal surgery
      not only should fully expose the spinal canal, completely resect the occupied
      position and remove the spinal cord compression, but also should maintain the
      stability of spinal biomechanics. Because of the different realization of
      clinician to safeguard and rebuild the spinal stabilization during opertion of
      spinal canal disease, and choice of surgical method and how to maintain the
      stability of spine biomechanics has become a hot of research in this field. Many
      scholars have studied it in order to reduce the influence of laminectomy on the
      spinal stability. Laminoplasty can directly relieve the nerve roots compression
      caused by increasing or reconstruction of vertebral canal volume, and allow the
      migration of spinal cord to dorsum and depart from disc and vertebral body.
      Laminoplasty not only can fully expose and decompress during operative, but also
      may prevent the postoperative spinal instability. In addition to these condition
      of extensive disease, severe bone destruction or combined with osteoporosis, the
      laminoplasty is the most ideal method for single spinal canal disease in
      theoretically.

PMID- 29350003
TI  - [Anatomical feature of lumbar and S1 pedicle in patients with thoracolumbar
      kyphosis secondary to ankylosing spondylitis].
AB  - OBJECTIVE: To measure the correlative parameters of vertebral pedicles from L1 to
      S1 by CT scan in the patients with thoracolumbar kyphosis secondary to ankylosing
      spondylitis(AS) and disc degenerative disease(DDD), and analyze their anatomical
      difference in order to provide the selection and placement of pedicle screw
      during operation. METHODS: The clinical data of 30 male AS patients (AS group)
      with the mean age of(35.7+/-9.5) years (ranged, 23 to 51) and 30 male DDD
      patients (DDD group) with the mean age of(52.4+/-8.9) years(ranged, 39 to 64)
      underwent surgery in our institution from March 2012 to November 2014 were
      analyzed. The CT scans of lumbar and sacrum were performed before surgery. The
      parameters of vertebral pedicle from L1 to S1 were measured and compared,
      including pedicle width (PW), pedicle screw path length (PL), pedicle height
      (PH), pedicle transverse angle (EA), and pedicle inclined angle (FA). Paired
      sample t-test was used to detect the divergence in the above-mentioned data
      between left and right sides. In addition, results between two groups were
      compared using independent sample t-test. RESULTS: The study showed that a
      gradual increase in the average pedicle width both AS group and DDD group from L1
      to S1. The average PW of AS group was bigger than DDD group in L5 and S1(P<0.05),
      it was(16.47+/-2.66) mm and (21.76+/-2.97)mm vs. (14.51+/-2.11)mm and (18.87+/
      2.14) mm respectively;the average PL of DDD group was smaller than AS group from
      L1 to S1(P<0.05); the both maximum of PL were in L3 segment; the average EA of AS
      group was smaller than DDD group from L1 to S1; the average FA of AS group was
      significantly smaller than DDD group from L3 to S1, (P<0.05), was(-2.88+/-10.24)
      degrees , (-7.88+/-10.22) degrees , (-7.70+/-10.40) degrees , (-5.15+/-10.25)
      degrees  vs. (4.05+/-2.21) degrees , (7.79+/-4.38) degrees , (7.07+/-3.21)
      degrees , (12.62+/-3.21) degrees , respectively. CONCLUSIONS: Increasing the
      strength of internal fixation is feasible to insert the larger and bigger pedicle
      screws in low lumbar and S1 among AS patients, while the EA should be decreased
      properly and the direction on the sagittal plane should be adjusted.

PMID- 29350004
TI  - [Posterior debridement and bone grafting via intervertebral space combined with
      internal fixation for the treatment of lumbosacral tuberculosis].
AB  - OBJECTIVE: To explore the clinical effects of posterior debridement, bone
      grafting via intervertebral space combined with internal fixation for the
      treatment of lumbosacral tuberculosis. METHODS: The clinical data of 32 patients
      with lumbosacral tuberculosis underwent the procedure of one-stage posterior
      intervertebral debridement, bone grafting and internal fixation from January 2007
      to July 2013 were retrospectively analyzed. There were 17 males and 15 females,
      aged from 27 to 63 years with an average of (49.8+/-9.2) years. The course of
      disease was from 5 to 18 months with the mean of (10.7+/-3.2) months. There was
      involved the vertebral body of L5 in 1 case, the intervertebral space of L5S1 in
      8 cases, and the vertebral body of L5 or S1 combined with intervertebral space of
      L5S1 in 23 cases. VAS, ESR, CRP, the lumbosacral angle, the height of
      intervertebral space of L5S1, and ASIA grade were used to evaluate clinical
      effects. RESULTS: All the patients were followed up from 18 to 39 months with an
      average of 21.6 months. Operative time was 120 to 260 min with the mean of 175
      min, and intraoperative bleeding was 700 to 1 450 ml with the mean of 1 050 ml.
      VAS before operation was 8.4+/-1.6, then descended to 3.5+/-0.8(P<0.05) on the
      3rd month after operation and redescended to the level of 1.7+/-0.6(P<0.05) at
      the final follow-up. The ESR and CRP before operation were (48.8+/-10.2) mm and
      (58.6+/-5.6) mg/L, respectively, then decreased to (35.6+/-6.9) mm and (22.5+/
      4.3) mg/L (P<0.05) at the 3rd month after operation and returned to the normal
      level at the final follow-up. The height of intervertebral space of L5S1 and
      lumbosacral angle before operation were (7.7+/-0.4) mm and (19.3+/-1.2) degrees ,
      respectively, then improved to (10.3+/-0.3) mm and (22.4+/-1.5) degrees  on the
      3rd month after operation(P<0.05), and maintained such level, no obvious lost at
      later. According to ASIA grade, 8 cases were grade C, 19 were grade D, 5 were
      grade E before operation, and at final follow-up, 1 case still was grade D,
      others were grade E. CONCLUSIONS: The procedure of posterior debridement, bone
      grafting via intervertebral space combined with internal fixation is an effective
      and safe method in treating lumbosacral tuberculosis, it can effectively debride
      tuberculose focus, maintain the spinal stability, and improve the dysfunction
      with less complication.

PMID- 29350005
TI  - [Relationship between the prediction of the opening angle and the increased value
      of cross-sectional area in single open-door laminoplasty].
AB  - OBJECTIVE: To evolve the formula of relationship between opening angle of
      laminoplasty and the increased value of cross-sectional area, and to predict the
      opening angle according to the opening size of lanminoplasty. METHODS: From
      January 2013 to December 2015, 26 patients underwent single open-door
      laminoplasty in C3-C7. Among them, 10 patients with ossification of posterior
      longitudinal ligament, there were 6 males and 4 females, aged from 39 to 58 years
      old with an average of 49.2 years; and 16 patients with cervical spondylotic
      myelopathy, there were 10 males and 6 females, aged from 40 to 58 years old with
      an average of 50.2 years. Through the changes of spinal canal shape between
      preoperation and postoperation to set up the regular geometric model, and to
      deduce the formula of the relationship between the opening angle of laminoplasty
      and the increased value of cross-sectional area, and predict the formula of
      opening angle. According to the preoperative and postoperative CT scan, the
      needed parameters were measured, and were substituted in the above formula to get
      the change of cross-sectional area before and after operation, predicting the
      opening angle of laminoplasty. The differences between the change of cross
      sectional area before and after operation, predictive the opening angle of
      laminoplasty and practical measured data were analyzed by statistical methods,
      thus to verify the feasibility of formula in practical application. RESULTS: All
      imaging data of 26 patients were obtained. There were significant differences in
      changes of cross-sectional areas in every patients (laminoplasty in C3 to C7)
      before and after operation in the same segment(P<0.01). The increasing extent in
      cross-sectional areas was gradually diminished following the opening angle
      increasing. There was no significant difference between the opening angle
      attained by formula and the data measured by software in the same
      segment(P>0.05). CONCLUSIONS: Increment of cross-sectional areas following C3-C7
      laminoplasty can be accurately attained and the opening angle can also be
      predicted by a certain formula, which can help surgeons to attain the accurate
      opening angle and reduce the postoperative complications.

PMID- 29350006
TI  - [The shor-term clinical outcomes and safety of extreme lateral interbody fusion
      combined with percutaneous pedicle screw fixation for the treatment of
      degenerative lumbar disease].
AB  - OBJECTIVE: To evaluate the early efficacy and safety of extreme lateral interbody
      fusion (XLIF) combined with percutaneous pedicle screw fixation for lumbar
      degenerative disease. METHODS: From January 2013 to June 2014, 13 patients with
      degenerative lumbar disease were treated with XLIF combined with percutaneous
      pedicle screw fixation, including 8 cases of lumbar instability, 5 cases of mild
      to moderate lumbar spondylolisthesis;there were 5 males and 8 females, aged from
      56 to 73 years with an average of 62.1 years. All patients were single segment
      fusion. Operation time, perioperative bleeding and perioperative complications
      were recorded. Visual analogue scale (VAS) and Oswestry Disability Index (ODI)
      were used to evaluate the clinical efficacy. Interbody fusion rate was observed
      and the intervertebral foramen area changes were compared preoperation and
      postoperation by X-rays and CT scanning. RESULTS: The mean operation time and
      perioperative bleeding in the patients respectively was(62.8+/-5.2) min
      and(82.5+/-22.6) ml. One case occurred in the numbness of femoribus internus and
      1 case occurred in the muscle weakness of hip flexion after operation, both of
      them recovered within 2 weeks. All the patients were followed up from 12 to 19
      months with an average of 15.6 months. VAS was decreased from preoperative 7.31+/
      0.75 to 2.31+/-0.75 at final follow-up(P<0.05); ODI was decreased from
      preoperative (42.58+/-1.55)% to (12.55+/-0.84)% at final follow-up(P<0.05). At
      final follow-up, CT scanning confirmed 8 cases completely fused and 5 cases
      partly fused;the intervertebral foramen area was increased from preoperative
      (94.86+/-2.44)mm2 to (150.70+/-7.02)mm2(P<0.05). CONCLUSIONS: Extreme lateral
      interbody fusion combined with percutaneous pedicle screw fixation is an ideal
      method and can obtain early good clinical effects in treating lumbar degenerative
      disease.

PMID- 29350007
TI  - [The metabolic profilings study of serum and spinal cord from acute spinal cord
      injury rats 1H NMR spectroscopy].
AB  - OBJECTIVE: To establish the rat model of acute spinal cord injury, followed by
      aprimary study on this model with 1H NMR based on metabonomics and to explore the
      metabonomics and biomarkers of spinal cord injury rat. METHODS: Twenty eight-week
      old adult male SD rats of clean grade, with body weight of (200+/-10) g, were
      divided into sham operation group and model group in accordance with the law of
      random numbers, and every group had 10 rats. The rats of sham operation group
      were operated without damaging the spinal cord, and rats of model group were made
      an animal model of spinal cord incomplete injury according to the modified
      Allen's method. According to BBB score to observate the motor function of rats on
      the 1th, 5th, and 7th days after surgery. Postoperative spinal cord tissue was
      collected in order to pathologic observation at the 7th day, and the metabolic
      profilings of serum and spinal cord from spinal cord injury rats were studied by
      1H NMR spectroscopy. RESULTS: The hindlimb motion of rats did not obviously
      change in sham operation group, there was no significant difference at each time
      point;and rats of model group occurred flaccid paralysis of both lower
      extremities, there was a significant difference at each time; there was
      significant differences between two groups at each time. Pathological results
      showed the spinal cord structure was normal with uniform innervation in shame
      group, while in model group, the spinal cord structure was mussy, and the neurons
      were decreased, with inflammatory cells and necrotic tissue. Analysis of
      metabonomics showed that concentration of very low density fat protein (VLDL),
      low density fat protein (LDL), glutamine, citric acid, dimethylglycine (DMG) in
      the serum and glutathione, 3-OH-butyrate, N-Acetyl-L-aspartic acid (NAA),
      glycerophosphocholine (GPC), glutamic acid, and ascorbate in spinal cord had
      significant changes(P<0.05). CONCLUSIONS: There are significant differences in
      metabolic profile from serum and spinal cord sample between model group and sham
      operation group, it conduces to explain the changes of small molecular substances
      in serum and spinal cord tissue after spinal cord injury, this provides the
      research basis for targeted research on the role of metabolic markers in patients
      with acute spinal cord injury.

PMID- 29350008
TI  - [Surgical treatment for open tarsometatarsal joint injury].
AB  - OBJECTIVE: To discuss the surgical method and clinical efficacy for open
      tarsometatarsal joint injuries. METHODS: From March 2011 to January 2015, 21
      patients with open tarsometatarsal joint injuries were treated with stage-surgery
      method, including 14 males and 7 females with an average age of 45.6 years old
      ranging from 20 to 75 years. Injury site occurred in the left foot of 13 cases
      and right foot of 8 cases. Traffic injury was in 5 cases, crush injury in 6
      cases, heavy crushing was in 10 cases. According to Myerson to classify for
      tarsometatarsal joint injury, 5 cases were type B2, 9 cases were type C1, and 7
      cases were type C2. And according to Gustilo to typing for soft tissue injury, 5
      cases were type IIB, 10 cases were type IIIA, 6 cases were type IIIB. Fracture
      healingand complications were observed after operation and clinical effects were
      evaluated according to the midfoot score of AOFAS. RESULTS: All the patients were
      followed up from 11 to 40 months with an average of 16.2 months. The fracture
      healing time was from 10 to 16 weeks with an average of 12.3 weeks. No
      complications such as deep infection, nonunion and osteomyelitis were found.
      Midfoot score of AOFAS at last follow-up was 83.0+/-14.9, 9 cases got excellent
      results, 8 good, 2 fair, 2 poor. Two patients complicated with severe traumatic
      arthritis once again underwent tarsometatarsal arthrodesis. CONCLUSIONS: For the
      treatment of open tarsometatarsal joint injury, reasonable debridement,
      comprehensive assessment for the soft tissue injury, correctly grasp the surgical
      indications and time of internal fixation, can reduce the incidence of deep
      infection and osteomyelitis.

PMID- 29350009
TI  - [Etiological analysis, preventional and therapeutical strategies for the
      unsatisfied cervical posterior decompression surgery].
AB  - OBJECTIVE: To discuss the causes of unsatisfied cervical posterior decompression
      surgery and describe the overhauling strategies and precaution. METHODS: The
      clinical data of 14 patients required revision surgery were retrospectively
      analyzed, and these patients with unsatisfied effects were due to cervical
      posterior decompression surgery from January 2012 to December 2014. Overhauling
      reasons were analyzed and then different revision procedures were performed. The
      functions of cervical cord and ambulation were evaluated respectively by modified
      Japanese Orthopedic Association(mJOA) score and Nurick grade according to the
      course order:preoperative for the first time, pre-revision and at final follow
      up. Improvement rate of nerves function were calculated before and after
      operation for the first time, before and after revision. Above data were
      statistically analyzed by SPSS16.0 software. RESULTS: Reoperation reasons
      including 2 patients with the insufficiency width of laminectomy, 2 patients with
      the inadequate length of decompression, 2 patients with nerve root and spinal
      cord compression caused by fractured collapse, 4 patients with closed the door of
      vertebral lamina, 1 patient with less open-door angle, 2 patiens with
      ossification of posterior longitudinal ligament (1 case complicated with close
      the door), 2 patients with cervical spine kyphotic deformity aggravating (1 case
      complicated with close the door), 1 patient with nerve root canal stenosis caused
      by uncovertebral joint hyperplasia. Preoperative for the first time, pre-revision
      and at final follow-up, mJOA scores were 11.89+/-1.67, 13.11+/-1.09, 15.61+/
      0.59, and Nurick grades were 4.21+/-0.58, 3.57+/-0.51, 1.71+/-0.47, respectively.
      There was significant difference between final follow-up and preoperative for the
      first time, pre-revision(P<0.05). Improvement rate of nerve function was (22.33+/
      9.49)% with bad before and after operation for the first time, and (64.60+/
      9.88)% with good before and after revision, with statistical
      significance(P<0.05). CONCLUSIONS: Individualized revision surgery based on
      different causes for unsatisfied cervical posterior decompression can improve the
      function of spinal cord. Preoperative carefully analyzing the etiological
      factors, thoroughly decompression can reduce the revision rate.

PMID- 29350010
TI  - [A comparative study of outcome between single cage and double cages interbody
      fusion combined with pedicle screw fixation in treatment of isthmic
      spondylolisthesis].
AB  - OBJECTIVE: To compare the clinical effects of isthmic spondylolisthesis by a
      single cage or double cages interbody fusion combined with pedicle screw
      fixation. METHODS: The clinical data of 172 patients with isthmic
      spondylolisthesis underwent surgery from March 2000 to August 2008 were
      retrospectively analyzed. All cases underwent posterior pedicle screw fixation
      and interbody fusion, 89 cases with single cage fusion and 83 cases with double
      cages fusion. In single cage group, there were 56 males and 33 females, aged from
      18 to 63 years old with an average of(41.60+/-8.20) years;25 cases were in L4
      segment and 64 cases were in L5;according to the Meyerding standard, 32 cases
      were I degree, 46 cases were II degree and 11 cases were III degree. In double
      cage group, there were 49 males and 34 females, aged from 20 to 65 years old with
      an average of(43.30+/-6.39) years;21 cases were in L4 and 62 cases were in
      L5;according to the Meyerding standard, 25 cases were I degrees, 45 cases were II
      degree, and 13 cases were III degree. The operative time, intraoperative blood
      loss, postoperative drainage volum, bone fusion rate, intervertebral space height
      and the improvement of clinical symptoms were compared between two groups.
      RESULTS: All the operations were successful and all patients were followed up for
      18 to 83 months with an average of 4 years and 3 months. The operative time,
      intraoperative blood loss, postoperative drainage volume in single cage group
      were less than of double cage group(P<0.05). Two weeks after operation, the
      intervertebral space height was significantly increased in two groups(P<0.05),
      and there was no significant difference at the last follow-up between two groups.
      At 16 months after operation, all bone grafts of patients got bony fusion by X
      rays. At the last follow-up, there were no statistically significant difference
      in JOA, ODI and VAS score between two groups, no pedicle screw loosening and
      breaking were found. CONCLUSIONS: Single cage interbody fusion combined with
      pedicle screw fixation is as effective as with double cages interbody fusion in
      treatment of isthmic spondylolisthesis, it has the advantages of short operative
      time and less blood loss.

PMID- 29350011
TI  - [Treatment of ossification of ligamentum flavum complicated with lumbar spinal
      stenosis].
AB  - OBJECTIVE: To investigate the imaging characteristic and operation outcome of
      ossification of ligamentum flavum with lumbar spinal stenosis. METHODS: January
      2013 to January 2016, 9 patients with ossification of ligamentum flavum with
      lumbar spinal stenosis were treated, included 5 males and 4 females, aged from 51
      to 63 years old with an average of 57 years old. All patients complained
      intermittent claudication and radiating pain at lower limb. The pathologic change
      regions examined by CT or MRI were as follows:2 cases in L4,5 and L5S1, 5 in L,,
      and 2 in L5S1. Four patients underwent simple laminectomy and 5 patients
      underwent laminectomy and discectomy, interbody fusion and internal fixation with
      pedicle screw. Clinical effects were evaluated according to JOA score, which
      items included subjective symptom, daily activity limitation, clinical sign and
      bladder function. RESULTS: No complications such as infection or nerve injury
      were found after operation. The follow-up period was from 12 to 60 months with an
      average of 24 months. The low back pain and radiating pain at lower limb improved
      significantly and walking distance approached normal at final follow-up;and JOA
      scores improved obviously. CONCLUSIONS: Ossification of ligamentum flavum has the
      special characteristic on CT scan, which decide the selection of operation
      method. The operative aim is effectively spinal decompression and rebuilding
      lower lumbar stability by minimally invasive surgery.

PMID- 29350012
TI  - [Application of debridement and bone autografting combined with proximal femoral
      anatomical plates for benign tumor in proximal femur].
AB  - OBJECTIVE: To explore the clinical effects of debridement and bone autografting
      combined with proximal femoral anatomical plate in treating benign tumor in
      proximal femur. METHODS: From January 2010 to October 2014, 30 patients with
      benign tumor in proximal femur were treated with debridement, autogenic ilium,
      autogenic ilium and allogeneic bone implant, and anatomic plate fixation. Among
      them, there were 13 males and 17 females aged from 12 to 68 years old with an
      average of 42 years old. The courses ranged from 1 month to 2 years with an
      average of 9 months. MSTS scoring were observed and compared before and after
      operation, and also applied to evaluate lower-extremity function. X-ray was
      examined to evaluate healing of focus. Postoperative complications were observed.
      RESULTS: All patients were followed up from 12 to 48 months with an average of 29
      months. MSTS score at the final following-up (27.06+/-2.59) was higher than
      preoperative (16.44+/-1.35), and there was significant difference(P<0.05). X-ray
      at the final following-up showed bone graft fusion, pathological fracture were
      recover consciously, internal fixation was well, no loosening, deformation and
      displacement occurred. One case occurred incision fat liquefaction and 1 patient
      with giant cell tumor of bone relapsed at 13 months after operation. CONCLUSIONS:
      Debridement and bone autografting combined with proximal femoral anatomical plate
      is an effective method in treating benign tumor in proximal femur. It could
      control tumor, relieve pain, promote function and prevent occurrence of
      pathologic fractures.

PMID- 29350013
TI  - [Closed reduction and percutaneous double K-wires internal fixation for the
      treatment of multisegmental fracture of humeral shaft].
AB  - OBJECTIVE: To observe the clinical effects of closed reduction and percutaneous
      double K-wires internal fixation in treating multisegmental fracture of humeral
      shaft. METHODS: From January 2009 to April 2015, 27 patients with multisegmental
      fracture of humeral shaft were treated with closed reduction and percutaneous
      double K-wires internal fixation, including 10 males and 17 females, ranging in
      age from 26 to 81 years with an average of 52 years;the disease course ranged
      from 2 hours to 6 days with an average of 1.5 days. Operative time,
      intraoperative blood loss, hospital stay, fracture healed time, complications
      were observed and recovery of shoulder joint function was evaluated by Constant
      Murley shoulder score. RESULTS: All the patients were followed up from 12 to 24
      weeks with an average of 16 weeks. Operative time was 20 to 40 min with an
      average of 28 min; intraoperative blood loss was 5 to 25 ml with an average of 10
      ml;hospital stay was 3 to 5 days with an average of 3.5 days. All fractures got
      bone healing and healed time was 12 to 22 weeks with average of 14 weeks.
      Postoperatively 1 case complicated with wire tail bulging and local irritation
      symptoms, and the symptoms disappeared when the wire was removed out after the
      fracture healing; 1 case complicated with local infection after wire tail
      disengaging, and recovered through anti-septic treatment. According to the
      Constant-Murley standard of shoulder joint function, 10 cases got excellent
      results, 15 good, 2 fair, with scores of 89.1+/-2.7. CONCLUSIONS: Closed
      reduction and percutaneous double K-wires fixation for the treatment of
      multisegmental fractures of humeral shaft have advantages of simpler
      manipulating, less bleeding, less invasive, less complications, and shoulder and
      elbow joint can obtain good recovery. But closed reduction and percutaneous
      double K-wires internal fixation cannot be effective against rotation and provide
      axial stability, the immoblization with a sling or other auxiliary methods should
      be applied.

PMID- 29350014
TI  - [A case report of hysterical paralysis during kyphoplasty in a patient with
      compression fracture of lumbar vertebra].

PMID- 29350015
TI  - [Application of finite element method in spinal biomechanics].
AB  - The finite element model is one of the most important methods in study of modern
      spinal biomechanics, according to the needs to simulate the various states of the
      spine, calculate the stress force and strain distribution of the different groups
      in the state, and explore its principle of mechanics, mechanism of injury, and
      treatment effectiveness. In addition, in the study of the pathological state of
      the spine, the finite element is mainly used in the understanding the mechanism
      of lesion location, evaluating the effects of different therapeutic tool,
      assisting and completing the selection and improvement of therapeutic tool, in
      order to provide a theoretical basis for the rehabilitation of spinal lesions.
      Finite element method can be more provide the service for the patients suffering
      from spinal correction, operation and individual implant design. Among the design
      and performance evaluation of the implant need to pay attention to the individual
      difference and perfect the evaluation system. At present, how to establish a
      model which is more close to the real situation has been the focus and difficulty
      of the study of human body's finite element.Although finite element method can
      better simulate complex working condition, it is necessary to improve the
      authenticity of the model and the sharing of the group by using many kinds of
      methods, such as image science, statistics, kinematics and so on.

PMID- 29350016
TI  - Biomarkers of treatment efficacy in patients with chronic spontaneous urticaria.
AB  - Summary: Background. Currently there are no biomarkers useful to predict the
      future evolution and the therapeutic response in patients with chronic
      spontaneous urticaria (CSU). Objective. To review the available information on
      biomarkers that might be applied for the follow up of the response to guideline
      recommended therapies for CSU. Methods. A review of the medical literature on CSU
      potential clinical and laboratory biomarkers in PubMed and MEDLINE including the
      terms urticaria, chronic urticaria, chronic idiopathic urticaria, chronic
      spontaneous urticaria, antihistamines (AHs), omalizumab (OMA), cyclosporine
      (CyA), and treatment. Results. Clinical manifestations that were associated to
      poor responses to AHs were atopy, asthma, rhinitis / rhinosinusitis, thyroid
      disease, hypertension, higher disease activity and duration. Laboratory markers
      of AH resistance that have been reported include Complement C5a fraction,
      Autologous Serum Skin Test (ASST), Basophil Activation Test (BAT), D-dimer and
      LCN2 adipokine. Basophil Histamine Release Assay (BHRA), ASST, and basophil
      CD203c-upregulating activity in the serum correlated with favorable response to
      OMA, whereas disease duration and severity, BAT, BHRA, and D-dimer levels were
      associated with better responses to CyA. Conclusion. Some promising biomarkers
      useful for patient management in CSU, have been identified in the literature.
      There is, however, an urgent need of new, easy-to-perform markers that can be
      made widely available for the optimal care of patients suffering CSU.

PMID- 29350017
TI  - Skin prick test analysis reveals cross-sensitization to tomato profilin and grass
      pollen in nasobronchialallergic patients with history of tomato food allergy.
AB  - Summary: The association between grass pollen sensitization and food allergy to
      tomato is of great interest. We report here, the first such study in Indian
      population. We investigated 246 allergic rhinitis / asthma patients by diagnostic
      case history and skin prick test (SPT); grass pollen mix, tomato extract and
      purified tomato profilin were used for SPT. Tomato profilin was purified by
      affinity chromatography, and analyzed by HPLC (95% purity) and SDS-PAGE (14 kDa).
      We observed that 38% of the patients had sensitization to both grass pollen and
      tomato fruit, of which 92% were sensitized to tomato profilin. Among patients
      with a history of food allergy to tomato fruit, the association was more
      pronounced (66%). Tomato profilin appears to be an important cross-sensitizing
      panallergen in respiratory allergic patients in the Indian subcontinent.

PMID- 29350018
TI  - Allergy and high trait anxiety are related to increases in heart rate
      variability: results of naturalistic long-term design study.
AB  - Summary: A number of studies report heart rate variability (HRV) changes in
      allergic as well as high trait anxious people, and associations between allergic
      inflammation and trait anxiety. This study investigated HRV of 20 low anxious
      allergic, 19 healthy high trait anxious and 18 healthy low anxious, in
      naturalistic setting. On arranged research days, subjects performed measurements
      using portable ECG device and subjective self-assessment of perceived stress.
      Five repeated measurements data from each subject have shown increases in overall
      HRV, as well as HRV on respiratory frequencies in both allergy and high trait
      anxiety. Subject's sex was an important factor, because HRV increases in allergy
      were only apparent in women. Data from self-assessment show no differences in
      experienced stress attributable to allergy, only to trait anxiety.

PMID- 29350019
TI  - Cypress pollen allergy is responsible for two distinct phenotypes of allergic
      rhinitis different from other pollinosis.
AB  - Summary: Different phenotypes of allergic rhinitis have been identified based on
      the seasonality of the allergen involved. Within pollinosis, importance has to be
      paid to the responsible pollen species. Guidelines for clinical management are
      mostly based on studies performed in patients with grass pollen allergy. Only few
      data is available on tree pollen allergy and more specifically on cypress pollen
      allergy. We focused on the clinical and biological features of cypress pollen
      allergy to determine whether it is associated with a specific phenotype of
      allergic rhinitis or not. Our results suggest that cypress pollen can be
      responsible for two distinct phenotypes of rhinitis, both different from other
      pollinosis. In the most common phenotype, cypress pollen was not responsible for
      bronchial hyperresponsiveness or systemic inflammation. Close attention has to be
      paid to the allergen involved in allergic rhinitis. Different phenotypes leading
      to different pharmacological strategies may apply.

PMID- 29350020
TI  - Cutaneous drug reactions to antiepileptic drugs and relation with HLA alleles in
      the Turkish population.
AB  - Summary: Background and objective. Many studies have shown associations between
      HLAB*15:02, HLA-A*31:01 and carbamazepine (CBZ)-induced delayed cutaneous
      hypersensitivity reactions. The aim of this study is to evaluate a possible
      association between delayed cutaneous reactions to antiepileptic drugs (AEDs) and
      certain HLA-A and HLA-B alleles in the Turkish population. Methods. The study
      consisted of 3 groups: Group I (reactive group) included the patients who had
      documented delayed cutaneous reactions to any antiepileptic drug. Group II (non
      reactive group) included the patients who have been on antiepileptic treatment at
      least for three months without any adverse reactions. Group III consisted of
      healthy subjects. The HLA-A and B alleles were analyzed in all groups. Results.
      Forty patients (29 female) had experienced different hypersensitivity reactions
      due to AEDs: maculopapular exanthema (26 patients), Stevens-Johnson syndrome (6
      patients), drug rash with eosinophilia and systemic symptoms (7 patients), toxic
      epidermal necrolysis (1 patient). Lamotrigine (11) and CBZ (10) were the most
      common culprit drugs involved in the reactions. The HLA-B*15:02 was not present
      in any of the study groups. However, HLA-B*35:02 was found in 4 patients from the
      reactive group, while it was not observed in non-reactive patients and was
      detected in only one healthy subject (p = 0.021). Conclusion. Although our
      preliminary results did not indicate a strong allele association with AED
      hypersensitivity, HLA-B*35:02 appears to be a candidate allele for MPE / DRESS /
      DIHSS induced by AED's in Turkish population. Further studies with a larger
      sample size may result in more comprehensive data about the genetic tendency for
      AED hypersensitivity in the Turkish population.

PMID- 29350021
TI  - Bodybuilding protein supplements and cow's milk allergy in adult.
AB  - Summary: We report a case of a previously healthy 24-year-old man with a 3-month
      history of gastrointestinal symptoms during exercise and also few minutes after
      the ingestion of cow's milk (CM) without exercise. He reported the ingestion of a
      blend of hydrolyzed whey and casein proteins for bodybuilding for the last 2
      years. The in vivo tests showed positivity to CM, alpha-lactalbumin, beta
      lactoglobulin and casein extracts, and also to the protein supplement. The serum
      specific IgE was positive for CM, beta-lactoglobulin and alpha-lactalbumin. The
      in vivo and in vitro tests results suggested an IgE-mediated CMA. Adult-onset CMA
      has been rarely reported, and to our knowledge this is the first case possibly
      related to bodybuilding supplements. The authors theorize that the presentation
      of large amounts of proteins in the gastrointestinal tract may favor
      sensitization.

PMID- 29350022
TI  - An unusual case of positive sIgE to Galactose-alpha-1,3-galactose from South
      Italy.
AB  - Summary: We report the case of a 38-year-old man who was bitten several times
      during his life by a tick. He didn't report any previous history of anaphylaxis
      after the ingestion of red meat. The serum specific IgE showed positivity to
      alpha-Gal. The proximity of the bits didn't increase the titer of IgE antibodies
      to alpha-gal. We could hypothesize that the frequency of the exposure to the tick
      Corresponding author bites and the amount of tick bites during his lifetime
      induced a sort of tolerance in this patient.

PMID- 29350023
TI  - Erratum to: Plasma betaine concentrations correlate with plasma cortisol but not
      with C-reactive protein in an elderly population

PMID- 29350025
TI  - Synthesis, Spectroscopy, and Morphology of Tetrastilbenoidmethanes.

PMID- 29350024
TI  - Accurate Quantification of Radiosulfur in Chemically Complex Atmospheric Samples.
AB  - An ultralow-level liquid scintillation counting (LSC) technique has been used in
      measuring radiosulfur (cosmogenic 35S) in natural samples. The ideal half-life of
      35S (~87 days) renders it a new way to examine various biogeochemical problems. A
      major limitation of the technique is that complex chemical compositions in
      atmospheric samples may lead to color quenching of LSC cocktails, a serious
      problem prolonging the pretreatment time (>1 week) and hampering the accurate
      determination of 35S. For application of the technique where many of the most
      important atmospheric chemical processes are examined, significant interferences
      arise and accurate analysis in small samples is not possible. In this study, we
      optimized the LSC method to minimize/eliminate color quenching in high
      sensitivity 35S measurements. The analytical performance of this new method was
      evaluated using control laboratory experiments and natural aerosol samples.
      Results show that the new method offers comparable accuracy as the traditional
      method for normal environmental samples [bias: <+/-0.03 disintegrations per
      minute (DPM)] and significantly shortens the pretreatment time to less than 3
      days. For samples that were heavily contaminated by color-quenching agents, the
      accuracy of this new method is notably higher than that of the traditional method
      (maximum bias: -0.3 vs -1.5 DPM). With the growing use of radiosulfur in the
      field of Earth and planetary sciences, the accurate determination of 35S would
      provide a reliable field-based constraint for modeling 35S production in the
      atmosphere and allow a wide range of atmospheric, hydrological, and
      biogeochemical applications.

PMID- 29350026
TI  - Steric and Acidity Control in Hydrogen Bonding and Proton Transfer to trans
      W(N2)2(dppe)2.
AB  - The interaction of trans-W(N2)2(dppe)2 (1; dppe = 1,2
      bis(diphenylphosphino)ethane) with relatively weak acids (p-nitrophenol,
      fluorinated alcohols, CF3COOH) was studied by means of variable temperature IR
      and NMR spectroscopy and complemented by DFT/B3PW91-D3 calculations. The results
      show, for the first time, the formation of a hydrogen bond to the coordinated
      dinitrogen, W-N=N...H-O, that is preferred over H-bonding to the metal atom,
      W...H-O, despite the higher proton affinity of the latter. Protonation of the
      core metal-the undesirable side step in the conversion of N2 to NH3-can be
      avoided by using weaker and, more importantly, bulkier acids.

PMID- 29350027
TI  - Evaluation of Drug Exposure and Metabolism in Locust and Zebrafish Brains Using
      Mass Spectrometry Imaging.
AB  - Studying how and where drugs are metabolized in the brain is challenging. In an
      entire organism, peripheral metabolism produces many of the same metabolites as
      those in the brain, and many of these metabolites can cross the blood-brain
      barrier from the periphery, thus making the relative contributions of hepatic and
      brain metabolism difficult to study in vivo. In addition, drugs and metabolites
      contained in ventricles and in the residual blood of capillaries in the brain may
      overestimate drugs' and metabolites' concentrations in the brain. In this study,
      we examine locusts and zebrafish using matrix assisted laser desorption
      ionization mass spectrometry imaging to study brain metabolism and distribution.
      These animal models are cost-effective and ethically sound for initial drug
      development studies.

PMID- 29350028
TI  - Anisotropic Electronic Characteristics, Adsorption, and Stability of Low-Index
      BiVO4 Surfaces for Photoelectrochemical Applications.
AB  - Many experimental results reveal different activities among different low-index
      surfaces of photocatalysts. The current investigation focuses on the theoretical
      understanding of the electronic characteristics, surface activity, and stability
      of different low-index surfaces of BiVO4 toward water splitting using first
      principle calculations. The results indicate that BiVO4 has four types of low
      index surfaces, namely, (010)T1, (010)T2, (110)T1, and (111)T1. The different
      band edge potentials of the surfaces, resulting from the variation of the
      electrostatic potential, lead to a higher oxidation ability for (010)T1 and
      (010)T2 than for (110)T1 and (111)T1 surfaces. The electrons prefer to accumulate
      on (010)T1 and (010)T2 surfaces, whereas holes like to accumulate on (110)T1 and
      (111)T1 surfaces during a photocatalytic process. Moreover, investigation on the
      adsorbed intermediates during the water-splitting process indicates that the
      oxygen evolution reaction on BiVO4 surfaces is mainly dominated by the reaction
      OH* <-> O* + H+ + e-, and (110)T1 and (111)T1 surfaces are energetically more
      favorable as photoanodes for water splitting than (010)T1 and (010)T2.
      Furthermore, the BiVO4 surface as photoanodes tend to be unstable and can easily
      be corroded with or without the presence of an oxidative environment, however,
      there is an exception for the BiVO4 (010)T1 and (010)T2 surfaces, which are
      thermodynamically stable in the solution when there are no strong oxidative
      species. These results provide important insights into the anisotropy behaviors
      among low-index surfaces of BiVO4 for photocatalytic reactions.

PMID- 29350030
TI  - Correction to "Tunneling Control of Chemical Reactions: The Third Reactivity
      Paradigm".

PMID- 29350029
TI  - Microwell Array Method for Rapid Generation of Uniform Agarose Droplets and Beads
      for Single Molecule Analysis.
AB  - Compartmentalization of aqueous samples in uniform emulsion droplets has proven
      to be a useful tool for many chemical, biological, and biomedical applications.
      Herein, we introduce an array-based emulsification method for rapid and easy
      generation of monodisperse agarose-in-oil droplets in a PDMS microwell array. The
      microwells are filled with agarose solution, and subsequent addition of hot oil
      results in immediate formation of agarose droplets due to the surface-tension of
      the liquid solution. Because droplet size is determined solely by the array unit
      dimensions, uniform droplets with preselectable diameters ranging from 20 to 100
      MUm can be produced with relative standard deviations less than 3.5%. The array
      based droplet generation method was used to perform digital PCR for absolute DNA
      quantitation. The array-based droplet isolation and sol-gel switching property of
      agarose enable formation of stable beads by chilling the droplet array at -20 
      degrees C, thus, maintaining the monoclonality of each droplet and facilitating
      the selective retrieval of desired droplets. The monoclonality of droplets was
      demonstrated by DNA sequencing and FACS analysis, suggesting the robustness and
      flexibility of the approach for single molecule amplification and analysis. We
      believe our approach will lead to new possibilities for a great variety of
      applications, such as single-cell gene expression studies, aptamer selection, and
      oligonucleotide analysis.

PMID- 29350031
TI  - Microbiota-Regulated Outcomes of Human Cancer Immunotherapy via the PD-1/PD-L1
      Axis.

PMID- 29350032
TI  - Structure and Gas Transport at the Polymer-Zeolite Interface: Insights from
      Molecular Dynamics Simulations.
AB  - We investigate the structure of polyimide (PI) at the surface of a silicalite
      zeolite (MFI), as part of a model hybrid organic-inorganic mixed matrix membrane
      system, through equilibrium molecular dynamics simulations. Furthermore, we
      report a comparison of the adsorption and transport characteristics of pure
      components CO2 and CH4 in PI, MFI, and PI-MFI composite membranes. It is seen
      that incorporation of MFI zeolite into PI results in the formation of densified
      polymer layers (rigidified region) near the surface, having thickness around 1.2
      nm, before bulklike behavior of the polymer is attained, contrary to empirical
      fits suggesting the existence of an approximately 1 MUm thick interface between
      the polymer and filler. This region offers an extra resistance to gas diffusion
      especially for the gas with a larger kinetic diameter, CH4, thus improving the
      CO2/CH4 kinetic selectivity in the PI-MFI composite membrane. Furthermore, we
      find that the kinetic selectivity of CO2 over CH4 in the rigidified region
      increases with temperature and that additivity of transport resistances in MFI,
      interfacial layer, and bulklike region of the polymer satisfactorily explains
      transport behavior in the composite sandwich investigated. The gas adsorption
      isotherms are extracted considering the dynamics and structural transitions in
      the PI and PI-MFI composite upon gas adsorption, and it is seen that the
      rigidified layer affects the gas adsorption in the polymer in the PI-MFI hybrid
      system. A significant increase in CO2/CH4 selectivity as well as gas permeability
      is observed in the PI-MFI composite membrane compared to that in the pure PI
      polymer membrane, which is correlated with the high selectivity of the rigidified
      interfacial layer in the polymer. Thus, while enhancing transport resistance, the
      rigidified layer is beneficial to membrane selectivity, leading to improved
      performance based on the Robeson upper bound plot for polymers.

PMID- 29350033
TI  - Impact of Backbone Pattern and Residue Substitution on Helicity in
      alpha/beta/gamma-Peptides.
AB  - We have evaluated the impact of changes in the chemical structure of peptidic
      oligomers containing alpha-, beta-, and gamma-amino acid residues
      (alpha/beta/gamma-peptides) on the propensities of these oligomers to adopt
      helical conformations in aqueous and alcoholic solutions. These studies were
      inspired by our previous discovery that alpha/beta/gamma-peptides containing a
      regular alphagammaalphaalphabetaalpha hexad repeat adopt an alpha-helix-like
      conformation in which the beta and gamma residues are aligned in a stripe along
      one side, and the remainder of the helix surface is defined by the alpha
      residues. This helix was found to be most stable when the beta and gamma residues
      were rigidified with specific cyclic constraints. Relaxation of the beta residue
      constraints caused profound conformational destabilization, but relaxation of the
      gamma residue constraints led to only a moderate drop in helicity. The new work
      more broadly characterizes the effect of gamma residue substitution on helix
      stability, based on circular dichroism and two-dimensional NMR measurements. We
      find that even a fully unsubstituted gamma residue (derived from gamma
      aminobutyric acid) supports a moderate helical propensity, which is surprising in
      light of the strong destabilizing effect of glycine residues on alpha-helix
      stability. Additional studies examine the effects of altering sequence in terms
      of amino acid type, by comparing a prototype with the
      alphagammaalphaalphabetaalpha hexad pattern to isomers with irregular
      arrangements of the alpha, beta, and gamma residues along the backbone. The data
      indicate that the strong helix-forming propensity previously discovered for
      alpha/beta/gamma-peptide 12-mers is retained when sequence is varied, with small
      variations detected across diverse alpha-beta-gamma placements. These structural
      findings suggest that alpha/beta/gamma-peptide scaffolds represent versatile
      scaffolds for the design of peptidic foldamers that display specific functions.

PMID- 29350034
TI  - Probing the Complexities of Structural Changes in Layered Oxide Cathode Materials
      for Li-Ion Batteries during Fast Charge-Discharge Cycling and Heating.
AB  - The rechargeable lithium-ion battery (LIB) is the most promising energy storage
      system to power electric vehicles with high energy density and long cycling life.
      However, in order to meet customers' demands for fast charging, the power
      performances of current LIBs need to be improved. From the cathode aspect, layer
      structured cathode materials are widely used in today's market and will continue
      to play important roles in the near future. The high rate capability of layered
      cathode materials during charging and discharging is critical to the power
      performance of the whole cell and the thermal stability is closely related to the
      safety issues. Therefore, the in-depth understanding of structural changes of
      layered cathode materials during high rate charging/discharging and the thermal
      stability during heating are essential in developing new materials and improving
      current materials. Since structural changes take place from the atomic level to
      the whole electrode level, combination of characterization techniques covering
      multilength scales is quite important. In many cases, this means using
      comprehensive tools involving diffraction, spectroscopy, and imaging to
      differentiate the surface from the bulk and to obtain structural/chemical
      information with different levels of spatial resolution. For example, hard X-ray
      spectroscopy can yield the bulk information and soft X-ray spectroscopy can give
      the surface information; X-ray based imaging techniques can obtain spatial
      resolution of tens of nanometers, and electron-based microcopy can go to
      angstroms. In addition to challenges associated with different spatial
      resolution, the dynamic nature of structural changes during high rate cycling and
      heating requires characterization tools to have the capability of collecting high
      quality data in a time-resolved fashion. Thanks to the advancement in synchrotron
      based techniques and high-resolution electron microscopy, high temporal and
      spatial resolutions can now be achieved. In this Account, we focus on the recent
      works studying kinetic and thermal properties of layer-structured cathode
      materials, especially the structural changes during high rate cycling and the
      thermal stability during heating. Advanced characterization techniques relating
      to the rate capability and thermal stability will be introduced. The different
      structure evolution behavior of cathode materials cycled at high rate will be
      compared with that cycled at low rate. Different response of individual
      transition metals and the inhomogeneity in chemical distribution will be
      discussed. For the thermal stability, the relationship between structural changes
      and oxygen release will be emphatically pointed out. In all these studies being
      reviewed, advanced characterization techniques are critically applied to reveal
      complexities at multiscale in layer-structured cathode materials.

PMID- 29350035
TI  - Selective Proton/Deuteron Transport through Nafion|Graphene|Nafion Sandwich
      Structures at High Current Density.
AB  - Ion current densities near 1 A cm-2 at modest bias voltages (<200 mV) are
      reported for proton and deuteron transmission across single-layer graphene in
      polyelectrolyte-membrane (PEM)-style hydrogen pump cells. The graphene is
      sandwiched between two Nafion membranes and covers the entire area between two
      platinum-carbon electrodes, such that proton transfer is forced to occur through
      the graphene layer. Raman spectroscopy confirms that buried graphene layers are
      single-layer and relatively free of defects following the hot-press procedure
      used to make the sandwich structures. Area-normalized ion conductance values of
      approximately 29 and 2.1 S cm-2 are obtained for proton and deuteron transport,
      respectively, through single-layer graphene, following correction for
      contributions to series resistance from Nafion resistance, contact resistance,
      etc. These ion conductance values are several hundred to several thousand times
      larger than in previous reports on similar phenomena. A ratio of proton to
      deuteron conductance of 14 to 1 is obtained, in good agreement with but slightly
      larger than those in prior reports on related cells. Potassium ion transfer rates
      were also measured and are attenuated by a factor of many thousands by graphene,
      whereas proton transfer is attenuated by graphene by only a small amount. Rates
      for hydrogen and deuterium ion exchange across graphene were analyzed using a
      model whereby each hexagonal graphene hollow site is assumed to transmit ions
      with a specific per-site ion-transfer self-exchange rate constant. Rate constant
      values of approximately 2500 s-1 for proton transfer and 180 s-1 for deuteron
      transfer per site through graphene are reported.

PMID- 29350036
TI  - Electrochemical and Spectral Characterization of Iron Corroles in High and Low
      Oxidation States:  First Structural Characterization of an Iron(IV) Tetrapyrrole
      pi Cation Radical.
AB  - The electrochemistry and spectroscopic properties of three iron corroles were
      examined in benzonitrile, dichloromethane, and pyridine containing 0.1 M tetra-n
      butylammonium perchlorate or tetra-n-ethylammonium hexafluorophosphate as
      supporting electrolyte. The investigated compounds are represented as
      (OEC)FeIV(C6H5), (OEC)FeIVCl, and (OEC)FeIII(py), where OEC is the trianion of
      2,3,7,8,12,13,17,18-octaethylcorrole. Each iron(IV) corrole undergoes two one
      electron reductions and two or three one-electron oxidations depending upon the
      solvent. Under the same solution conditions, the iron(III) corrole undergoes a
      single one-electron reduction and one or two one-electron oxidations. Each singly
      oxidized and singly reduced product was characterized by UV-vis and/or EPR
      spectroscopy. The data indicate a conversion of (OEC)FeIV(C6H5) and (OEC)FeIVCl
      to their iron(III) forms upon a one-electron reduction and to iron(IV) corrole pi
      cation radicals upon a one-electron oxidation. The metal center in
      [(OEC)FeIII(C6H5)]- is low spin (S = 1/2) as compared to electrogenerated
      [(OEC)FeIIICl]-, which contains an intermediate-spin (S = 3/2) iron(III).
      (OEC)FeIII(py) also contains an intermediate-spin-state iron(III) and, unlike
      previously characterized (OEC)FeIII(NO), is converted to an iron(IV) corrole upon
      oxidation rather than to an iron(III) pi cation radical. Singly oxidized
      [(OEC)FeIV(C6H5)]*+ is the first iron(IV) tetrapyrrole pi cation radical to be
      isolated and was structurally characterized as a perchlorate salt. It
      crystallizes in the triclinic space group P1 with a = 10.783(3) A, b = 13.826(3)
      A, c = 14.151(3) A, alpha = 78.95(2) degrees , beta = 89.59(2) degrees , and
      gamma = 72.98(2) degrees  at 293 K with Z = 2. Refinement of 8400 reflections and
      670 parameters against F o2 yields R1 = 0.0864 and wR2 = 0.2293. The complex
      contains a five-coordinated iron with average Fe-N bond lengths of 1.871(3) A.
      The formulation of the electron distribution in this compound was confirmed by
      Mossbauer, X-ray crystallographic, and magnetic susceptibility data as well as by
      EPR spectroscopy, which gives evidence for strong antiferromagnetic coupling
      between the iron(IV) center and the singly oxidized corrole macrocycle.

PMID- 29350037
TI  - Oxidation of Isodiphenylfluorindine: Routes to 13-Oxoisodiphenylfluorindinium
      Perchlorate and Fluorindine Cruciform Dimers.
AB  - Isodiphenylfluorindine (5) reacts with K2Cr2O7/H+ to give 13
      oxoisodiphenylfluorindinium perchlorate (7) (75%), but with phenyliodine
      bis(trifluoroacetate) (PIFA) or MnO2 it gives the zwitterionic and quinoidal
      cruciform 13,13'-dimers 11 (85%) and 12 (89%), respectively. The zwitterionic
      13,13'-dimer 11 can be rapidly converted with MnO2 into the quinoidal 13,13'
      dimer 12 (100%). UV-vis, NMR, single-crystal X-ray diffraction, and density
      functional theory studies support the structural assignments of all products. The
      electrochemical behavior of the compounds is also presented.

PMID- 29350038
TI  - Efficient Mass Spectral Analysis of Active Transporters Overexpressed in
      Escherichia coli.
AB  - Structural analysis of purified active membrane proteins can be performed by mass
      spectrometry (MS). However, no large-scale expression systems for active
      eukaryotic membrane proteins are available. Moreover, because membrane proteins
      cannot easily be digested by trypsin and ionized, they are difficult to analyze
      by MS. We developed a method for mass spectral analysis of eukaryotic membrane
      proteins combined with an overexpression system in Escherichia coli. Vesicular
      glutamate transporter 2 (VGLUT2/SLC17A6) with a soluble alpha-helical protein and
      histidine tag on the N- and C-terminus, respectively, was overexpressed in E.
      coli, solubilized with detergent, and purified by Ni-NTA affinity chromatography.
      Proteoliposomes containing VGLUT2 retained glutamate transport activity. For MS
      analysis, the detergent was removed from purified VGLUT2 by trichloroacetic acid
      precipitation, and VGLUT2 was then subjected to reductive alkylation and tryptic
      digestion. The resulting peptides were detected with 88% coverage by matrix
      assisted laser desorption ionization time-of-flight (MALDI-TOF) MS with or
      without liquid chromatography. Vesicular excitatory amino acid transporter and
      vesicular acetylcholine transporter were also detected with similar coverage by
      the same method. Thus this methodology could be used to analyze purified
      eukaryotic active transporters. Structural analysis with chemical modifiers by MS
      could have applications in functional binding analysis for drug discovery.

PMID- 29350039
TI  - Rhodium(III)-Catalyzed Directed C-H Coupling with Methyl Trifluoroacrylate:
      Diverse Synthesis of Fluoroalkenes and Heterocycles.
AB  - An example of Rh-catalyzed C-H activation with methyl trifluoroacrylate for the
      synthesis of fluoroolefins and heterocycles (benzoindolizines) is reported. The
      types of products were determined by the directing group. The benzoindolizines
      and fluoroolefins were obtained by using pyridine and pyrazole as the directing
      group, correspondingly. These transformations present a number of advantages,
      such as oxidant-free reaction conditions and broad functional group tolerance.
      Moreover, this reaction greatly extends the application of fluoroolefins.

PMID- 29350041
TI  - Chemo-, Regio-, and Enantioselective Rhodium-Catalyzed Allylation of Triazoles
      with Internal Alkynes and Terminal Allenes.
AB  - The rhodium-catalyzed asymmetric N1-selective and regioselective coupling of
      triazole derivatives with internal alkynes and terminal allenes gives access to
      secondary and tertiary allylic triazoles in very good enantioselectivities. For
      this process, three new members of the JosPOphos ligand family have been prepared
      and employed in catalysis. The optimized reaction conditions enable the coupling
      of triazoles with internal alkynes as well as with allenes, displaying a high
      tolerance for functional groups. A gram scale reaction provided N1-allyltriazole,
      which was subjected to various transformations highlighting synthetic utility.

PMID- 29350040
TI  - Formal (4 + 1)-Addition of Allenoates to o-Quinone Methides.
AB  - The first (4 + 1)-annulation of o-quinone methides with alpha-branched allenoates
      as C1 synthons has been developed. This operationally simple protocol gives
      access to highly functionalized dihydrobenzofurans in an unprecedented fashion
      with excellent diastereoselectivities and high yields.

PMID- 29350042
TI  - Application of Sulfur Ylides in 1,2-Difunctionalization of Arynes via Insertion
      into a C-S sigma-Bond.
AB  - A novel reactivity of sulfur ylides has been demonstrated in a transition-metal
      free protocol to access ortho-substituted thioanisole derivatives by insertion of
      arynes into a C-S sigma-bond in moderate to good yields. The reaction involves
      the formation of C-C and C-S bonds and consecutive breaking of two C-S bonds
      under operationally mild reaction conditions.

PMID- 29350043
TI  - The Acid-Free Cyclopropanol-Minisci Reaction Reveals the Catalytic Role of Silver
      Pyridine Complexes.
AB  - A well-defined homogeneous silver precatalyst can be utilized for the direct C-H
      functionalization of a wide range of aromatic nitrogen heterocycles with
      cyclopropanols under acid-free conditions. This reaction can be conducted on gram
      scale and with low catalyst loadings (as low as 1%), which is rare for silver
      catalyzed Minisci-type reactions. Moreover, reactivity trends, as well as steric
      and calculated electronic properties of the heterocycles, strongly suggest that
      silver-heterocycle complexes formed in situ behave as redox active catalysts and
      as Lewis acid activators of the heterocycle and that the electronic nature of the
      heterocyclic substrates tunes the reactivity of the resulting complexes.

PMID- 29350044
TI  - Enhanced Thermal Stability in Perovskite Solar Cells by Assembling 2D/3D Stacking
      Structures.
AB  - Two-dimensional (2D) perovskites have been shown to be more stable than their
      three-dimensional (3D) counterparts due to the protection of the organic ligands.
      Herein a method is introduced to form 2D/3D stacking structures by the reaction
      of 3D perovskite with n-Butylamine (BA). Different from regular treatment with n
      Butylammonium iodide (BAI) where 2D perovskite with various layers form, the
      reaction of BA with MAPbI3 only produce (BA)2PbI4, which has better protection
      due to more organic ligands in (BA)2PbI4 than the mixture of 2D perovskites.
      Compared to BAI treatment, BA treatment results in smoother 2D perovskite layer
      on 3D perovskites with a better coverage. The photovoltaic devices with 2D/3D
      stacking structures show much improved stability in comparison to their 3D
      counterparts when subjected to heat stress tests. Moreover, the conversion of
      defective surface into 2D layers also induces passivation of the 3D perovskites
      resulting in an enhanced efficiency.

PMID- 29350045
TI  - Total Synthesis of (-)-Xestosaprol N and O.
AB  - The first total synthesis of (-)-xestosaprol N and O is described. This synthetic
      work features a convergent strategy: (1) a Pd-catalyzed arylation followed by
      cyclization to build a naphthalene fragment (ring C, D); (2) utilization of (-)
      quinic acid to construct the chiral hydroxyl group at C-2; (3) a substrate
      controlled intramolecular Heck reaction to construct a quaternary carbon center
      (ring B); (4) introduction of a hypotaurine moiety at a late stage to furnish the
      E ring.

PMID- 29350046
TI  - Catalytic Enantioselective Reaction of 2H-Azirines with Thiols Using Cinchona
      Alkaloid Sulfonamide Catalysts.
AB  - The first catalytic enantioselective reaction of 2H-azirines with thiols has been
      developed. The obtained aziridines can be converted to optically active
      oxazolines, aziridylamides, or alpha-sulfonyl esters. Transformation of these
      optically active aziridines showed that 2H-azirines act as beta,beta
      dicarbocationic amine synthons.

PMID- 29350047
TI  - Removable Water-Soluble Olefin Metathesis Catalyst via Host-Guest Interaction.
AB  - A highly removable N-heterocyclic carbene ligand for a transition-metal catalyst
      in aqueous media via host-guest interactions has been developed. Water-soluble
      adamantyl tethered ethylene glycol in the ligand leads a hydrophobic inclusion
      into the cavity of beta-cyclodextrin. Ruthenium (Ru) olefin metathesis catalyst
      with this ligand demonstrated excellent performance in various metathesis
      reactions in water as well as in CH2Cl2, and removal of residual Ru was performed
      via filtration utilizing a host-guest interaction and extraction.

PMID- 29350048
TI  - Triple-split-bolus versus single-bolus CT in abdominal trauma patients: a
      comparative study.
AB  - Background Split-bolus computed tomography (CT) is a recent development in trauma
      imaging. Instead of multiple scans in different contrast phases after a single
      contrast bolus, split-bolus protocols consist of one single scan of the thorax
      and abdomen after two or three contrast injections at different points of time.
      Purpose To evaluate and compare image quality and injury findings of a new triple
      split-bolus CT (TS-CT) protocol of thorax and abdomen with those of a portal
      venous phase CT (PV-CT) in the same patient group. Material and Methods Trauma
      patients in 2009-2012 who underwent both the TS-CT initially and a PV-CT during
      the next six weeks were included. The TS-CT examination was performed as one CT
      run after application of three contrast boluses (total 175 mL) to enhance renal
      pelvis and urinary tract, the abdominal organs, and the large arterial vessels.
      The PV-CT had a fixed delay of 85 s. We measured attenuation in Hounsfield units
      (HU), evaluated possible organ injury and assessed image quality on a 5-point
      scale. Results Thirty-five patients were included. Attenuation measurements of
      major abdominal vessels, organs, and renal pelvis were significantly higher with
      the TS-CT protocol. Performance in organ injury diagnosis and image quality was
      equal in both protocols. Conclusion The overall performance of the TS-CT protocol
      is similar to the standard PV-CT. Excellent visualization of the arterial tree
      and the collecting system may eliminate the need for separate scans.

PMID- 29350050
TI  - Marital Status and Trajectories of Depressive Symptoms Among Older Adults of
      Mexican Descent.
AB  - Little is known about the implications of marital status for the age patterning
      of depressive symptoms in later life. Drawing on seven waves of data from the
      Hispanic Established Population for the Epidemiologic Study of the Elderly, this
      research uses growth curve models to examine age trajectories of depressive
      symptoms among continuously married and recently and continuously widowed older
      adults of Mexican descent (aged 65 years and older; N = 1,452). The findings
      demonstrate that despite having a higher mean level of depressive symptoms, the
      recently widowed experienced a similar rate of increase in distress with age to
      that of their married counterparts. Compared with the married, the continuously
      widowed had a steeper rise in depressive symptoms with age, although they had
      fewer symptoms at younger ages in later life. Physical health, financial strain,
      social support, and church attendance might account to a certain extent for
      marital status differences in depressive symptoms across later life.

PMID- 29350052
TI  - Protective mechanisms of 6-gingerol in dextran sulfate sodium-induced chronic
      ulcerative colitis in mice.
AB  - Ulcerative colitis (UC) is a relapsing and remitting inflammatory disease of the
      colon, with an increasing incidence worldwide. 6-Gingerol (6G) is a bioactive
      constituent of Zingiber officinale, which has been reported to possess various
      biological activities. This study was designed to evaluate the role of 6G in
      chronic UC. Chronic UC was induced in mice by three cycles of 2.5% dextran
      sulfate sodium (DSS) in drinking water. Each cycle consisted of 7 days of 2.5%
      DSS followed by 14 days of normal drinking water. 6G (100 mg/kg) and a reference
      anti-colitis drug sulfasalazine (SZ) (100 mg/kg) were orally administered daily
      to the mice throughout exposure to three cycles of 2.5% DSS. Administration of 6G
      and SZ significantly prevented disease activity index and aberrant crypt foci
      formation in DSS-treated mice. Furthermore, 6G and SZ suppresses immunoexpression
      of tumor necrosis factor alpha, interleukin-1beta, inducible nitric oxide
      synthase, Regulated on activation, normal T cell expressed and secreted (RANTES),
      and Monocyte chemoattractant protein-1 (MCP-1) in the DSS-treated mice. 6G
      effectively protected against colonic oxidative damage by augmenting the
      antioxidant status with marked decrease in lipid peroxidation levels in DSS
      treated mice. Moreover, 6G significantly inhibited nuclear factor kappa B (P65),
      p38, cyclooxygenase-2, and beta-catenin whereas it enhanced IL-10 and adenomatous
      polyposis coli expression in DSS-treated mice. In conclusion, 6G prevented DSS
      induced chronic UC via anti-inflammatory and antioxidative mechanisms and
      preservation of the Wnt/beta-catenin signaling pathway.

PMID- 29350051
TI  - HSA-based multi-target combination therapy: regulating drugs' release from HSA
      and overcoming single drug resistance in a breast cancer model.
AB  - Multi-drug delivery systems, which may be promising solution to overcome
      obstacles, have limited the clinical success of multi-drug combination therapies
      to treat cancer. To this end, we used three different anticancer agents,
      Cu(BpT)Br, NAMI-A, and doxorubicin (DOX), to build human serum albumin (HSA)
      based multi-drug delivery systems in a breast cancer model to investigate the
      therapeutic efficacy of overcoming single drug (DOX) resistance to cancer cells
      in vivo, and to regulate the drugs' release from HSA. The HSA complex structure
      revealed that NAMI-A and Cu(BpT)Br bind to the IB and IIA sub-domain of HSA by N
      donor residue replacing a leaving group and coordinating to their metal centers,
      respectively. The MALDI-TOF mass spectra demonstrated that one DOX molecule is
      conjugated with lysine of HSA by a pH-sensitive linker. Furthermore, the release
      behavior of three agents form HSA can be regulated at different pH levels.
      Importantly, in vivo results revealed that the HSA-NAMI-A-Cu(BpT)Br-DOX complex
      not only increases the targeting ability compared with a combination of the three
      agents (the NAMI-A/Cu(BpT)Br/DOX mixture), but it also overcomes DOX resistance
      to drug-resistant breast cancer cell lines.

PMID- 29350053
TI  - 8-isopentenyl isoflavone derivatives from the whole herb of Sphaerophysa salsula.
AB  - Phytochemical studies on the whole herb of Sphaerophysa salsula has resulted in
      the discovery of one new 8-isopentenyl isoflavone derivative, named sphaerosin s2
      (3-(8-(2-hydroxypropan-2-yl)-3,4-dihydro-2H-furo[2,3-h]chromen-3-yl)-2,6
      dimethoxyphenol) (1), along with four know 8-isopentenyl isoflavone derivatives
      (2-5). Compounds (2, 4 and 5) were isolated for the first time from this species.
      Their structures were elucidated on the basis of ESI-MS, UV, IR, 1D NMR and 2D
      NMR data.

PMID- 29350054
TI  - Caloinophyllin A, a new chromanone derivative from Calophyllum inophyllum roots.
AB  - A new chromanone derivative, namely caloinophyllin A (1), along with eight known
      compounds (2-9), nobiletin (2), pentamethylquercetin (3), 3,5,7,4'
      tetramethoxyflavone (4), 5,7,4'-trimethoxyflavone (5), 1,5-dihydroxyxanthone (6),
      1,8-dimethoxy-2-hydroxyxanthone (7), 1,6-dihydroxy-7-methoxyxanthone (8) and 4
      methoxycaffeic acid (9) were isolated from the roots of Calophyllum inophyllum.
      The structures of all the isolated compounds (1-9) were fully characterised using
      spectroscopic data, as well as comparison with the previous literature data. In
      addition, the quantum chemical calculation has been used to confirm the
      conformation of 1. Moreover, all isolated compounds were assessed for their in
      vitro cytotoxicity against five human cancer cell lines.

PMID- 29350049
TI  - Targeted and Off-Target (Bystander and Abscopal) Effects of Radiation Therapy:
      Redox Mechanisms and Risk/Benefit Analysis.
AB  - SIGNIFICANCE: Radiation therapy (from external beams to unsealed and sealed
      radionuclide sources) takes advantage of the detrimental effects of the clustered
      production of radicals and reactive oxygen species (ROS). Research has mainly
      focused on the interaction of radiation with water, which is the major
      constituent of living beings, and with nuclear DNA, which contains the genetic
      information. This led to the so-called target theory according to which cells
      have to be hit by ionizing particles to elicit an important biological response,
      including cell death. In cancer therapy, the Poisson law and linear quadratic
      mathematical models have been used to describe the probability of hits per cell
      as a function of the radiation dose. Recent Advances: However, in the last 20
      years, many studies have shown that radiation generates "danger" signals that
      propagate from irradiated to nonirradiated cells, leading to bystander and other
      off-target effects. CRITICAL ISSUES: Like for targeted effects, redox mechanisms
      play a key role also in off-target effects through transmission of ROS and
      reactive nitrogen species (RNS), and also of cytokines, ATP, and extracellular
      DNA. Particularly, nuclear factor kappa B is essential for triggering self
      sustained production of ROS and RNS, thus making the bystander response similar
      to inflammation. In some therapeutic cases, this phenomenon is associated with
      recruitment of immune cells that are involved in distant irradiation effects
      (called "away-from-target" i.e., abscopal effects). FUTURE DIRECTIONS:
      Determining the contribution of targeted and off-target effects in the clinic is
      still challenging. This has important consequences not only in radiotherapy but
      also possibly in diagnostic procedures and in radiation protection.

PMID- 29350056
TI  - New isolates from leaves of Nicotiana tabacum and their biological activities.
AB  - Three new isolates (1-3) including one new sterol and two new flavonoids together
      with three known sterols (4-6) were isolated from the leaves of Nicotiana
      tabacum. Their structures were determined mainly by spectroscopic methods,
      including extensive 1D and 2D NMR techniques. All compounds were evaluated for
      their anti-tobacco mosaic virus and cytotoxic activities. The results showed that
      compounds 2 and 3 exhibited high anti-TMV activity with inhibition rate of 34.2
      and 33.4%, respectively, which were roughly equivalent to that of positive
      control. The cytotoxicities of compounds 1 and 4-6 against five human tumour cell
      lines were also tested, and tested compounds showed weak inhibitory activities
      against some tested human tumour cell lines.

PMID- 29350057
TI  - Comment on 'Effect of marijuana use on cardiovascular and cerebrovascular
      mortality'.

PMID- 29350058
TI  - The challenge of risk prediction: How good are we?

PMID- 29350055
TI  - Therapeutic strategies and nano-drug delivery applications in management of
      ageing Alzheimer's disease.
AB  - In recent years, the incidental rate of neurodegenerative disorders has increased
      proportionately with the aging population. Alzheimer's disease (AD) is one of the
      most commonly reported neurodegenerative disorders, and it is estimated to
      increase by roughly 30% among the aged population. In spite of screening numerous
      drug candidates against various molecular targets of AD, only a few candidates -
      such as acetylcholinesterase inhibitors are currently utilized as an effective
      clinical therapy. However, targeted drug delivery of these drugs to the central
      nervous system (CNS) exhibits several limitations including meager solubility,
      low bioavailability, and reduced efficiency due to the impediments of the blood
      brain barrier (BBB). Current advances in nanotechnology present opportunities to
      overcome such limitations in delivering active drug candidates. Nanodrug delivery
      systems are promising in targeting several therapeutic moieties by easing the
      penetration of drug molecules across the CNS and improving their bioavailability.
      Recently, a wide range of nano-carriers, such as polymers, emulsions, lipo
      carriers, solid lipid carriers, carbon nanotubes, metal based carriers etc., have
      been adapted to develop successful therapeutics with sustained release and
      improved efficacy. Here, we discuss few recently updated nano-drug delivery
      applications that have been adapted in the field of AD therapeutics, and future
      prospects on potential molecular targets for nano-drug delivery systems.

PMID- 29350059
TI  - A new curriculum to address dementia-related stigma: Preliminary experience with
      Alzheimer's Association staff.
AB  - Objective Develop and test a stigma awareness and education curriculum targeted
      to non-medical staff of a local Alzheimer's Association chapter. Methods The
      curriculum, developed in collaboration with leadership and educational staff from
      the Cleveland Chapter of the Alzheimer's Association, included a definition,
      types, and domains of stigma; effects of stigma on individuals with dementia and
      their families; stigma evaluation studies; tips to address the topic of dementia
      related stigma with individuals and families. Lastly, an interactive discussion
      of real-life scenarios facilitated stigma recognition and management. Results
      Most staff felt the training improved their ability to identify Alzheimer's
      disease stigma, made them more comfortable talking about stigma, and would change
      the way they interacted with people and families impacted by Alzheimer's disease.
      Conclusions This brief, practical educational curriculum has potential to improve
      awareness of dementia stigma in Alzheimer's Association staff. Research is needed
      to expand stigma awareness in individuals and groups with varying levels of
      dementia knowledge.

PMID- 29350060
TI  - "So they are not alive?": Dementia, reality disjunctions and conversational
      strategies.
AB  - In some conversations involving persons with Alzheimer's disease, the
      participants may have to deal with the difficulty that they do not share a common
      ground in terms of not only who is alive or dead, but even more, who could
      possibly be alive. It is as if the participants face a reality disjunction. There
      are very few empirical studies of this difficulty in conversations involving
      persons with Alzheimer's disease or other kinds of dementia diagnoses. Often
      studies of confabulation have a focus on the behavior and experience of the
      healthy participants, but rarely on the interaction and the collaborative
      contributions made by the person with dementia. In the present article, we
      discuss various strategies used by all participants in an everyday conversation.
      The material consists of an hour long everyday conversation between a woman with
      Alzheimer's disease and two healthy participants (relatives). This conversation
      is analyzed by looking at the organization of the interaction with an emphasis on
      how the participants deal with instances of reality disjunctions. The result from
      the analysis demonstrates that both the healthy participants as well as the
      person with dementia together skillfully avoid the face threats posed by reality
      disjunctive contributions by not pursuing argumentative lines that in the end
      might jeopardize both the collaborative and the personal relations.

PMID- 29350062
TI  - Telotristat ethyl: a novel agent for the therapy of carcinoid syndrome diarrhea.
AB  - Carcinoid syndrome (CS), characterized by diarrhea and flushing, is present in
      20% of patients with neuroendocrine tumors at diagnosis and becomes more frequent
      with progression. The diarrhea of CS is caused mainly by tumoral secretion of
      serotonin. It may not be fully controlled by somatostatin analogs, the currently
      indicated drugs for symptomatic relief. Telotristat ethyl is a novel inhibitor of
      tryptophan hydroxylase, the rate-limiting enzyme in serotonin biosynthesis.
      Administration of the drug decreases diarrhea in patients with CS. Telotristat
      ethyl was approved in February 2017 (USA) and September 2017 (European
      Commission) for the treatment of CS diarrhea in adults inadequately controlled by
      somatostatin analog alone. This drug is expected to greatly improve the health
      and quality of life of patients with CS diarrhea.

PMID- 29350063
TI  - A qualitative interview study of people living with well-controlled Type 1
      diabetes.
AB  - OBJECTIVE: While many people with Type 1 diabetes find it difficult to achieve
      recommended blood glucose levels, a minority do achieve good control. Our study
      was conceived by patient and public (PP) partners and sought to learn about
      experiences of people living with well-controlled diabetes. DESIGN: A
      collaboration between academic health psychologists and five PP partners with
      experience of diabetes, who were trained to conduct and analyse semi-structured
      interviews. Fifteen adults with well-controlled Type 1 diabetes were interviewed
      about the history of their diabetes and their current self-management practices.
      Interviews were subjected to inductive thematic analysis. RESULTS: Eight sub
      themes were arranged into two overarching themes, 'facing up to diabetes' and
      'balance leads to freedom'. Participants described a process of acceptance and
      mastery of diabetes, and talked about how they gained a deeper understanding of
      bodily processes through trial and error. CONCLUSION: Based on the experiences of
      people with well-controlled Type 1 diabetes, interventions for people with this
      condition should encourage acceptance of the diagnosis and increasing confidence
      to experiment with behaviours (trial and error) to encourage 'mastery' of self
      management. The research collaboration described here is an example of best
      practice for future researchers wanting to actively engage PP partners.

PMID- 29350064
TI  - Comparison of hyaluronic acid-based micelles and polyethylene glycol-based
      micelles on reversal of multidrug resistance and enhanced anticancer efficacy in
      vitro and in vivo.
AB  - Polyethylene glycol (PEG)-based block copolymer micelles and hyaluronic acid (HA)
      based grafted copolymer micelles have been widely investigated in chemotherapy.
      In this study, to evaluate the differences among HA-based grafted polymer
      micelles, PEG-based block polymer micelles and the mixed of these two micelles in
      enhancing antitumor effects and overcoming MDR, two amphiphilic vitamin E
      succinate (VES) derivatives, HA VES (HA-g-VES) and PEG 2000 VES (TPGS2k), were
      applied as nanocarriers to prepare HA-VES micelles (HA-PMs), TPGS2k micelles
      (TPGS2k-PMs) and the mixed micelles (HA/TPGS2k-PMs) for the co-delivery of
      doxorubicin (DOX) and curcumin (Cur). With the addition of TPGS2k, the particle
      size of HA/TPGS2k-PMs (153.37 +/- 1.00 nm) was smaller than that of HA-PMs
      (223.83 +/- 1.84) but significantly larger than that of TPGS2k-PMs (about 20 nm).
      The loading efficiency of HA/TPGS2k-PMs was 7.10%, which was lower than HA-PMs
      (8.31 +/- 0.15%) but higher than TPGS2k-PMs (4.38 +/- 0.24%). In vitro, HA/TPGS2k
      PMs and TPGS2k-PMs exhibited higher cytotoxicity and reversal MDR effects than HA
      PMs in MCF-7/Adr cells. However, HA/TPGS2k-PMs, HA-PMs and TPGS2k-PMs all
      significantly improved the tumor biodistribution, the antitumor effects and
      reduced the side effects of DOX in 4T1-tumor-bearing mice, but these three
      micelles displayed no differences in vivo. Therefore, EPR passive targeting
      effects caused by PEGylated micelles and CD44 active targeting effects caused by
      HA-based micelles have no significant variance in the delivery of antitumor drugs
      by i.v.

PMID- 29350065
TI  - Molecular typing of Lactobacillus brevis isolates from Korean food using
      repetitive element-polymerase chain reaction.
AB  - Lactobacillus brevis is a part of a large family of lactic acid bacteria that are
      present in cheese, sauerkraut, sourdough, silage, cow manure, feces, and the
      intestinal tract of humans and rats. It finds its use in food fermentation, and
      so is considered a "generally regarded as safe" organism. L. brevis strains are
      extensively used as probiotics and hence, there is a need for identifying and
      characterizing these strains. For identification and discrimination of the
      bacterial species at the subspecific level, repetitive element-polymerase chain
      reaction method is a reliable genomic fingerprinting tool. The objective of the
      present study was to characterize 13 strains of L. brevis isolated from various
      fermented foods using repetitive element-polymerase chain reaction. Repetitive
      element-polymerase chain reaction was performed using three primer sets, REP,
      Enterobacterial Repetitive Intergenic Consensus (ERIC), and (GTG)5, which
      produced different fingerprinting patterns that enable us to distinguish between
      the closely related strains. Fingerprinting patterns generated band range in
      between 150 and 5000 bp with REP, 200-7500 bp with ERIC, and 250-2000 bp with
      (GTG)5 primers, respectively. The Jaccard's dissimilarity matrices were used to
      obtain dendrograms by the unweighted neighbor-joining method using genetic
      dissimilarities based on repetitive element-polymerase chain reaction
      fingerprinting data. Repetitive element-polymerase chain reaction proved to be a
      rapid and easy method that can produce reliable results in L. brevis species.

PMID- 29350061
TI  - The Adverse Effects of Environmental Noise Exposure on Oxidative Stress and
      Cardiovascular Risk.
AB  - Epidemiological studies have provided evidence that traffic noise exposure is
      linked to cardiovascular diseases such as arterial hypertension, myocardial
      infarction, and stroke. Noise is a nonspecific stressor that activates the
      autonomous nervous system and endocrine signaling. According to the noise
      reaction model introduced by Babisch and colleagues, chronic low levels of noise
      can cause so-called nonauditory effects, such as disturbances of activity, sleep,
      and communication, which can trigger a number of emotional responses, including
      annoyance and subsequent stress. Chronic stress in turn is associated with
      cardiovascular risk factors, comprising increased blood pressure and
      dyslipidemia, increased blood viscosity and blood glucose, and activation of
      blood clotting factors, in animal models and humans. Persistent chronic noise
      exposure increases the risk of cardiometabolic diseases, including arterial
      hypertension, coronary artery disease, diabetes mellitus type 2, and stroke.
      Recently, we demonstrated that aircraft noise exposure during nighttime can
      induce endothelial dysfunction in healthy subjects and is even more pronounced in
      coronary artery disease patients. Importantly, impaired endothelial function was
      ameliorated by acute oral treatment with the antioxidant vitamin C, suggesting
      that excessive production of reactive oxygen species contributes to this
      phenomenon. More recently, we introduced a novel animal model of aircraft noise
      exposure characterizing the underlying molecular mechanisms leading to noise
      dependent adverse oxidative stress-related effects on the vasculature. With the
      present review, we want to provide an overview of epidemiological, translational
      clinical, and preclinical noise research addressing the nonauditory, adverse
      effects of noise exposure with focus on oxidative stress. Antioxid. Redox Signal.
      28, 873-908.

PMID- 29350066
TI  - Differential expression of cytokeratin 14 and 18 in bladder cancer tumorigenesis.
AB  - It has been previously suggested that cytokeratins (CKs) are important diagnostic
      and prognostic biomarkers for urothelial lesions. Hence it is imperative to
      understand the expression pattern of cytokeratins during formation of papillary
      bladder cancer, which was the objective of the current study. Expression pattern
      of CK14 and CK18 were examined using immunohistochemical staining in a mice model
      of papillary bladder cancer. Twenty female mice were divided into two groups
      group 1 (NT) and group 2, which received N-butyl- N-(4-hydroxybutyl) nitrosamine
      (BBN) for 20 weeks plus one week without treatment. Following histological
      classification of bladder lesions, CK14 and CK18 immunostaining was assessed
      according to its distribution and intensity. In NT animals, both basal cells and
      umbrella cells showed sporadic positive staining for CK14 and CK18, respectively.
      In BBN group, hyperplastic lesions showed significantly more CK14 and
      significantly less CK18 staining ( P < 0.05 in each case). Invasive carcinomas
      showed increased CK14 immunostaining in all epithelial layers. Cumulatively, our
      data indicate that altered CK14 (high) and CK18 (low) expression is perhaps an
      early event in bladder cancer tumorigenesis in females at least and is
      characteristic of both urothelial superficial pre-neoplastic and neoplastic
      lesions. Impact statement Studies have shown that expression of cytokeratins
      (CKs) or their altered distribution affects the bladder cancer pathogenesis and
      disease outcome, while the underlying mechanisms are not clear. The present study
      aims to explore the expression pattern of CK14 and CK18 during formation of
      papillary bladder cancer. The results showed that hyperplastic lesions showed
      significantly more CK14 and significantly less CK18 staining and invasive
      carcinomas showed increased CK14 immunostaining in all epithelial layers in N
      butyl- N-(4-hydroxybutyl)nitrosamine (BBN)-induced mouse model. The results
      indicate that altered CK14 (high) and CK18 (low) expression is perhaps an early
      event in bladder cancer tumorigenesis and is characteristic of both urothelial
      superficial pre-neoplastic and neoplastic lesions, which may provide the early
      diagnosis index.

PMID- 29350067
TI  - Soluble Neuregulin1 is strongly up-regulated in the rat model of Charcot-Marie
      Tooth 1A disease.
AB  - Neuregulin1 (NRG1) is a growth factor playing a pivotal role in peripheral nerve
      development through the activation of the transmembrane co-receptors ErbB2-ErbB3.
      Soluble NRG1 isoforms, mainly secreted by Schwann cells, are strongly and
      transiently up-regulated after acute peripheral nerve injury, thus suggesting
      that they play a crucial role also in the response to nerve damage. Here we show
      that in the rat experimental model of the peripheral demyelinating neuropathy
      Charcot-Marie-Tooth 1A (CMT1A) the expression of the different NRG1 isoforms
      (soluble, type alpha and beta, type a and b) is strongly up-regulated, as well as
      the expression of NRG1 co-receptors ErbB2-ErbB3, thus showing that CMT1A nerves
      have a gene expression pattern highly reminiscent of injured nerves. Because it
      has been shown that high concentrations of soluble NRG1 negatively affect
      myelination, we suggest that soluble NRG1 over-expression might play a negative
      role in the pathogenesis of CMT1A disease, and that a therapeutic approach, aimed
      to interfere with NRG1 activity, might be beneficial for CMT1A patients. Further
      studies will be necessary to test this hypothesis in animal models and to
      evaluate NRG1 expression in human patients. Impact statement Charcot-Marie
      Tooth1A (CMT1A) is one of the most frequent inherited neurological diseases,
      characterized by chronic demyelination of peripheral nerves, for which effective
      therapies are not yet available. It has been recently proposed that the treatment
      with soluble Neuregulin1 (NRG1), a growth factor released by Schwann cells
      immediately after acute nerve injury, might be effective in CMT1A treatment.
      However, the expression of the different isoforms of endogenous NRG1 in CMT1A
      nerves has not been yet investigated. In this preliminary study, we demonstrate
      that different isoforms of soluble NRG1 are strongly over-expressed in CMT1A
      nerves, thus suggesting that a therapeutic approach based on NRG1 treatment
      should be carefully reconsidered. If soluble NRG1 is over-expressed also in human
      CMT1A nerves, a therapeutic approach aimed to inhibit (instead of stimulate) the
      signal transduction pathways driven by NRG1 might be fruitfully developed.
      Further studies will be necessary to test these hypotheses.

PMID- 29350069
TI  - New and developing pharmacotherapy for osteoporosis in men.
AB  - INTRODUCTION: Osteoporosis represents a major health and societal burden in men,
      as well as in women. However, only a minority of men are screened and treated for
      osteoporosis and fracture prevention, even after first fracture. Areas covered:
      This article provides a comprehensive summary of the currently available drugs
      for osteoporosis in men as well as insights into new and developing
      pharmacotherapy. Expert opinion: To date, therapeutic approaches to osteoporosis
      in men remain not as well defined as in women, since antifracture efficacy data
      are lacking for most approved pharmaceuticals. Based on the currently available
      evidence, bisphosphonates are generally recommended as first line pharmacotherapy
      in men. Conceptually, osteoanabolic agents, such as teriparatide could be more
      appropriate for men with primary osteoporosis and low bone turnover. However,
      osteoanabolic agents display a limited anabolic window during which their
      stimulatory effects on bone formation prevail over the increase in bone
      resorption and their use, for theoretical safety reasons, is limited to a
      cumulative duration of two years. Due to the recent advances in bone biology,
      future drugs for osteoporosis in men might include more selective antiresorptive
      compounds which do not markedly inhibit bone formation as well as newer
      osteoanabolic agents that appear to more selectively stimulate bone formation.

PMID- 29350070
TI  - Celiac antibodies in children with type 1 diabetes - A diagnostic validation
      study.
AB  - INTRODUCTION: Autoimmune diseases, such as celiac disease (CD) and diabetes
      mellitus type 1, tend to co-occur within the same patient. The prevalence of CD
      in diabetic children is higher than in the general population, and is estimated
      to be 0.6-16.4%. The diagnosis of CD is based on histopathological examination
      and serological testing, however, these methods are still imperfect and new
      diagnostic algorithms should be considered. AIM: The aim of the study was to
      assess the diagnostic value of serological tests detecting antibodies against
      deamidated gliadin peptide, endomysium, tissue transglutaminase, neo-epitope
      tissue transglutaminase and to identify HLA-related genetic predisposition to CD
      in patients with type 1 diabetes mellitus (DM1). METHODS: Autoantibodies were
      measured in the sera of 392 children suffering from DM1 aged 1-19 years old (mean
      11.76 +/- 4.14 years old). Additionally, PCR-based assessment of HLA DQ2/DQ8
      genotyping was performed. RESULTS: A positive result of at least one serological
      test was obtained from 81 children (20.66%). The sensitivity and specificity were
      76.47% and 91.67% for anti-DGP IgA, 70.59% and 58.33% for IgG anti-DGP,
      respectively. A positive predictive value was 100% for the anti-TG IgA at cutoff
      levels of 5 and 10 times higher than upper limit of reference values. HLA DQ2
      and/or DQ8 were found in 97.6% of examined children. CONCLUSIONS: Tests based on
      anti-TG IgA are more accurate for detecting CD in children with type 1 diabetes
      than anti-DGP IgA. A high percentage of diabetic children carry HLA alleles
      predisposing to CD, which indicates that genetic screening in this group of
      patients is not obligated.

PMID- 29350068
TI  - Primary Liver Cancers-Part 1: Histopathology, Differential Diagnoses, and Risk
      Stratification.
AB  - Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) are the 2 most common
      primary malignant liver tumors, with hepatocellular and bile ductular
      differentiation, respectively. This article reviews the key histopathological
      findings of these 2 primary liver cancers and includes a review of the role of
      ancillary testing for differential diagnosis, risk stratification according to
      the American Joint Committee on Cancer (AJCC) staging recommendation, and a
      review of precancerous lesions. A literature review was conducted to identify
      articles with information relevant to precancerous precursors, current
      histopathological classification, ancillary testing, and risk stratification of
      primary malignant liver tumors. The histomorphology of normal liver, preinvasive
      precursors, primary malignancies, and morphological variants, and the utilization
      of ancillary tests for the pathological diagnosis are described. Dysplastic
      nodules are the preinvasive precursors of HCC, and intraductal papillary
      neoplasms of bile ducts and biliary intraepithelial neoplasia are the preinvasive
      precursors of CC. Benign liver nodules including focal nodular hyperplasia and
      adenomas are included in this review, since some forms of adenomas progress to
      HCC and often they have to be differentiated from well-differentiated HCC. A
      number of morphological variants of HCC have been described in the literature,
      and it is necessary to be aware of them in order to render the correct diagnosis.
      Risk stratification is still dependent on the AJCC staging system. The diagnosis
      of primary liver carcinomas is usually straightforward. Application of the
      appropriate ancillary studies aids in the differential diagnosis of difficult
      cases. The understanding of the carcinogenesis of these malignancies has improved
      with the standardization of the pathological classification of preinvasive
      precursors and studies of the molecular pathogenesis. Risk stratification still
      depends on pathological staging.

PMID- 29350071
TI  - Disclosing respiratory co-infections: a broad-range panel assay for avian
      respiratory pathogens on a nanofluidic PCR platform.
AB  - Respiratory syndromes (RS) are among the most significant pathological conditions
      in edible birds and are caused by complex coactions of pathogens and
      environmental factors. In poultry, low pathogenic avian influenza A viruses,
      metapneumoviruses, infectious bronchitis virus, infectious laryngotracheitis
      virus, Mycoplasma spp. Escherichia coli and/or Ornithobacterium rhinotracheale in
      turkeys are considered as key co-infectious agents of RS. Aspergillus sp.,
      Pasteurella multocida, Avibacterium paragallinarum or Chlamydia psittaci may also
      be involved in respiratory outbreaks. An innovative quantitative PCR method,
      based on a nanofluidic technology, has the ability to screen up to 96 samples
      with 96 pathogen-specific PCR primers, at the same time, in one run of real-time
      quantitative PCR. This platform was used for the screening of avian respiratory
      pathogens: 15 respiratory agents, including viruses, bacteria and fungi
      potentially associated with respiratory infections of poultry, were targeted.
      Primers were designed and validated for SYBR green real-time quantitative PCR and
      subsequently validated on the Biomark high throughput PCR nanofluidic platform
      (Fluidigm(c), San Francisco, CA, USA). As a clinical assessment, tracheal swabs
      were sampled from turkeys showing RS and submitted to this panel assay. Beside
      systematic detection of E. coli, avian metapneumovirus, Mycoplasma gallisepticum
      and Mycoplasma synoviae were frequently detected, with distinctive co-infection
      patterns between French and Moroccan flocks. This proof-of-concept study
      illustrates the potential of such panel assays for unveiling respiratory co
      infection profiles in poultry.

PMID- 29350072
TI  - A new polyoxygenated abietane diterpenoid from the rattans of Bauhinia championii
      (Benth.) Benth.
AB  - A new polyoxygenated abietane diterpenoid, bauchampine A (1), together with seven
      known compounds (2-8), were isolated from the rattans of Bauhinia championii
      (Benth.) Benth. The structure of 1 was elucidated by extensive spectroscopic
      methods and the known compounds were identified by comparison with the data
      reported in the literature. New compound 1 was evaluated for its anti-rheumatoid
      arthritis activity via examining its anti-proliferative effect on synoviocytes in
      vitro. Compound 1 exhibited inhibitory effect on the proliferation of
      synoviocytes with IC50 value comparable to that of methotrexate.

PMID- 29350073
TI  - In their own words: a synthesis of the qualitative research on the experiences of
      adults seeking asylum. A systematic review of qualitative findings in forced
      migration.
AB  - Quantitative research indicates that some forced migrants have mental health
      needs. Asylum seekers are a group of forced migrants applying for asylum status
      in a host country, and are often subject to rights restrictions and threat of
      deportation, though little is known about subjective experiences of the asylum
      journey and process of claiming asylum. The current paper therefore describes a
      systematic review of the qualitative literature, examining asylum seekers
      experiences of asylum journey, from country of origin, to arrival and adaptation
      to host countries. A search of four databases yielded 122 studies.
      Inclusion/exclusion criteria were applied and 15 studies were retained and
      critically appraised. The country where research was conducted, study aims,
      sample characteristics and methodological approaches were all critically reviewed
      for included studies. Study aims fell into four themes; 'an aspect of the asylum
      seeker journey'; 'psychological distress and wellbeing'; 'cultural identity and
      adaptation to new environment' and 'social welfare, employment and housing'.
      Studies were generally high quality and indicate issues around choice of asylum
      destination, distress created by uncertainty around asylum decision and hostile
      reactions of host communities. However, few studies have examined the experiences
      of asylum seekers specifically, which is important given the unique circumstances
      of this population.

PMID- 29350074
TI  - Serum concentration and clinical significance of brain-derived neurotrophic
      factor in patients with Parkinson's disease or essential tremor.
AB  - Objectives The serum concentration of brain-derived neurotrophic factor (BDNF)
      was compared among patients with Parkinson's disease (PD), patients with
      essential tremor (ET), and healthy participants, and its association with
      clinical features of PD and ET was assessed. Methods Demographic and clinical
      data were collected from 60 patients with PD at different clinical stages, 60
      patients with ET, and 60 controls. All participants' serum BDNF concentrations
      were measured. Their motor abilities and activity were assessed by the Unified PD
      Rating Scale and the Hoehn and Yahr (H-Y) staging scale. Results Serum BDNF was
      significantly lower in patients with PD than in patients with ET and controls.
      BDNF decreased only in the early disease stages (H-Y stages I and II), but
      increased markedly in the advanced stages (H-Y stages III-V). There was no
      significant difference between patients with ET and controls. The BDNF
      concentration was negatively correlated with age at PD onset and positively
      associated with disease duration, severity of PD symptoms, and treatment with L
      DOPA. Conclusions A low serum BDNF concentration may serve as a biomarker in the
      early stages of PD, whereas a high concentration with PD progression may be due
      to treatment with L-DOPA in the advanced stages.

PMID- 29350075
TI  - Characterization of the proteome and lipidome profiles of human lung cells after
      low dose and chronic exposure to multiwalled carbon nanotubes.
AB  - The effects of long-term chronic exposure of human lung cells to multi-walled
      carbon nanotubes (MWCNT) and their impact upon cellular proteins and lipids were
      investigated. Since the lung is the major target organ, an in vitro normal
      bronchial epithelial cell line model was used. Additionally, to better mimic
      exposure to manufactured nanomaterials at occupational settings, cells were
      continuously exposed to two non-toxic and low doses of a MWCNT for 13-weeks.
      MWCNT-treatment increased ROS levels in cells without increasing oxidative DNA
      damage and resulted in differential expression of multiple anti- and pro
      apoptotic proteins. The proteomic analysis of the MWCNT-exposed cells showed that
      among more than 5000 identified proteins; more than 200 were differentially
      expressed in the treated cells. Functional analyses revealed association of these
      differentially regulated proteins to cellular processes such as cell death and
      survival, cellular assembly, and organization. Similarly, shotgun lipidomic
      profiling revealed accumulation of multiple lipid classes. Our results indicate
      that long-term MWCNT-exposure of human normal lung cells at occupationally
      relevant low-doses may alter both the proteome and the lipidome profiles of the
      target epithelial cells in the lung.

PMID- 29350076
TI  - Health Care Public Sector Share and the U.S. Life Expectancy Lag: A Country-level
      Longitudinal Study.
AB  - Growing research on the political economy of health has begun to emphasize
      sociopolitical influences on cross-national differences in population health
      above and beyond economic growth. While this research investigates the impact of
      overall public health spending as a share of GDP ("health care effort"), it has
      for the most part overlooked the distribution of health care spending across the
      public and private spheres ("public sector share"). I evaluate the relative
      contributions of health care effort, public sector share, and GDP to the large
      and growing disadvantage in U.S. life expectancy at birth relative to peer
      nations. I do so using fixed effects models with data from 16 wealthy democratic
      nations between 1960 and 2010. Results indicate that public sector share has a
      beneficial effect on longevity net of the effect of health care effort and that
      this effect is nonlinear, decreasing in magnitude as levels rise. Moreover,
      public sector share is a more powerful predictor of life expectancy at birth than
      GDP per capita. This study contributes to discussions around the political
      economy of health, the growth consensus, and the American lag in life expectancy.
      Policy implications vis-a-vis the U.S. Affordable Care Act are discussed.

PMID- 29350077
TI  - In hospital with a hearing impaired child - How parents experience communication
      between nurses and their child
AB  - Background: In daily communication, children with hearing impairment are
      restricted and dependent on their parents' help. In case of a hospitalisation,
      the risk of insufficient information and resulting traumatisation for those
      children is high. The aim of this study is the investigation of the communicative
      needs of the children concerned in order to avoid negative consequences of a
      hospitalisation and of inappropriate communication by nursing staff. Aim: This
      study explores how parents of a child with hearing impairment experience the
      communication between the nursing staff and their hospitalised child. Method: The
      study was conducted together with an advisory centre for hearing-impaired
      children, where most of the parents could be recruited. Narrative, semi
      structured interviews were conducted. The transcribed interviews were analysed
      according to the method of interpretative phenomenology. Results: The parents
      expressed their wish for affectionate verbal and nonverbal love and care for
      their child. They often experienced the nursing staff having little time, that
      there was no continuity and that the communicative needs of the child were not
      recognised. Since the parents did not think the nursing staff were capable of
      communicating with the child and because they wanted to protect him or her, they
      adopted a mediating role. Conclusions: Besides the sensitisation of the nursing
      staff, time resources, continuity, professional knowledge and benevolence in the
      nursing care of a child with hearing impairment play a fundamental role.

PMID- 29350078
TI  - External Control of Knowledge of Results: Learner Involvement Enhances Motor
      Skill Transfer.
AB  - Providing the learner control over aspects of practice has improved the process
      of motor skill acquisition, and self-controlled knowledge of results (KR)
      schedules have shown specific advantages over externally controlled ones. A
      possible explanation is that self-controlled KR schedules lead learners to more
      active task involvement, permitting deeper information processing. This study
      tested this explanatory hypothesis. Thirty undergraduate volunteers of both
      sexes, aged 18 to 35, all novices in the task, practiced transporting a tennis
      ball in a specified sequence within a time goal. We compared a high-involvement
      group (involvement yoked, IY), notified in advance about upcoming KR trials, to
      self-controlled KR (SC) and yoked KR (YK) groups. The experiment consisted of
      three phases: acquisition, retention, and transfer. We found both IY and SC
      groups to be superior to YK for transfer of learning. Postexperiment participant
      questionnaires confirmed a preference for receiving KR after learner-perceived
      good trials, even though performance on those trials did not differ from
      performance on trials without KR. Equivalent IY and SC performances provide
      support for the benefits of task involvement and deeper information processing
      when KR is self-controlled in motor skill acquisition.

PMID- 29350079
TI  - Differences in home blood pressure and pulse rates between singleton and twin
      pregnancies.
AB  - Objectives To evaluate home blood pressure (HBP) measurements during pregnancy
      and postpartum and investigate differences between singleton and twin
      pregnancies. Methods This prospective study involved normotensive, pregnant women
      who were planning to give birth at Saitama Medical Centre, Saitama, Japan between
      September 2013 and March 2017. HBP and pulse rate were measured twice daily and
      clinical blood pressure values were determined from patient records. Results HBP
      values were available from 101 participants; 69 women with singleton and 32 women
      with twin pregnancies. Systolic BP was statistically significantly higher in twin
      pregnancies from 23 weeks of gestation until 8 weeks after delivery compared with
      singleton pregnancies. Pulse rate was also statistically significantly higher
      between 11 and 30 weeks gestation in women with twin pregnancies compared with
      those with singleton pregnancies. Conclusions BP monitoring is important in the
      management of twin pregnancies, especially during the later gestational weeks and
      postpartum period and HBP would facilitate this monitoring.

PMID- 29350080
TI  - IRF2BP2-RARA t(1;17)(q42.3;q21.2) APL blasts differentiate in response to all
      trans retinoic acid.

PMID- 29350081
TI  - Assessment of the anterolateral ligament of the knee by 1.5 T magnetic resonance
      imaging.
AB  - Objective This study was performed to evaluate the visibility of the knee's
      anterolateral ligament (ALL) by magnetic resonance (MR) imaging when evaluating
      injuries of the ALL in relation to injuries of the anterior cruciate ligament
      (ACL). Methods Two reviewers retrospectively analyzed MR images for the
      visibility and dimensions of the ALL and the relationship between ALL and ACL
      injuries. The intraclass correlation coefficient (ICC) and kappa analysis were
      used to assess interobserver reliability. The chi-square test was used to assess
      the relationship between ALL and ACL injuries. Results The entire ALL was viewed
      on 82% of all MR images. The ICC for ALL visualization ranged from moderate to
      perfect between the two readers. There was almost perfect agreement between the
      reviewers when evaluating ALL dimensions. The mean length +/- standard error,
      median thickness, and mean width +/- standard error of the ALL were 36.5 +/- 0.6
      mm, 2.5 mm, and 8.2 +/- 0.2 mm, respectively. A statistically significant
      relationship was observed between ALL and ACL injuries. Conclusion The ALL was
      visible on most MR images, allowing ALL injuries to be noted during routine MR
      image interpretation. Radiologists should note concomitant ACL and ALL injuries
      as part of their assessments.

PMID- 29350083
TI  - From "a Fair Game" to "a Form of Covert Research": Research Ethics Committee
      Members' Differing Notions of Consent and Potential Risk to Participants Within
      Social Media Research.
AB  - Social media (SM) research presents new challenges for research ethics committees
      (RECs) who must balance familiar ethical principles with new notions of public
      availability. This article qualitatively examines how U.K. REC members view this
      balance in terms of risk and consent. While it found significant variance
      overall, there were discernible experience-based trends. REC members with less
      experience of reviewing SM held inflexible notions of consent and risk that could
      be categorized as either relying on traditional notions of requiring direct
      consent, or viewing publicly available data as "fair game." More experienced REC
      members took a more nuanced approach to data use and consent. We conclude that
      the more nuanced approach should be best practice during ethical review of SM
      research.

PMID- 29350082
TI  - Quantitative DTI metrics in a canine model of Krabbe disease: comparisons versus
      age-matched controls across multiple ages.
AB  - Purpose The purpose of this study was to compare quantitative diffusion tensor
      imaging metrics in dogs affected with a model of Krabbe disease to age-matched
      normal controls. We hypothesized that fractional anisotropy would be decreased
      and radial diffusivity would be increased in the Krabbe dogs. Methods We used a
      highly reproducible region-of-interest interrogation technique to measure
      fractional anisotropy and radial diffusivity in three different white matter
      regions within the internal capsule and centrum semiovale in four Krabbe affected
      brains and three age-matched normal control brains. Results Despite all four
      Krabbe dogs manifesting pelvic limb paralysis at the time of death, age-dependent
      differences in DTI metrics were observed. In the 9, 12, and 14 week old Krabbe
      dogs, FA values unexpectedly increased and RD values decreased. FA values were
      generally higher and RD values generally lower in both regions of the internal
      capsule in the Krabbe brains during this period. FA values in the brain from the
      16 week old Krabbe dog decreased and were lower than in control brains and RD
      values increased and were higher than in control brain. Conclusion Our findings
      suggest that FA and RD in the internal capsule and centrum semiovale are affected
      differently at different ages, despite disease having progressed to pelvic limb
      paralysis in all dogs evaluated. In 9, 12, and 14 week old Krabbe dogs, higher FA
      values and lower RD values are seen in the internal capsule. However, in the 16
      week old Krabbe dog, lower FA and higher RD values are seen, consistent with
      previous observations in Krabbe dogs, as well as observations in human Krabbe
      patients.

PMID- 29350084
TI  - Exploring assistive technology use to support cognition in college students with
      histories of mild traumatic brain injury.
AB  - PURPOSE: College students with mild traumatic brain injury (mTBI) may experience
      chronic cognitive deficits necessitating use of external supports for daily task
      completion. The purpose of this study was to explore cognitive support system
      selection and use by students with histories of mTBI when completing novel
      prospective memory tasks. MATERIALS AND METHODS: We implemented a multiple case
      study, sequential explanatory mixed-methods design with three participants.
      Participants completed four experimental phases: (1) background history
      collection, cognitive assessment completion, pre-trial interview, and selection
      of two external supports for trial phase use; (2) trial Phase 1 (i.e., 10-days);
      (3) trial Phase 2 (i.e., 10 days); and (4) post-trial exit interview. We examined
      participants' support type and characteristic preferences and evaluated task
      execution accuracy when implementing differing supports. RESULTS: Participants
      expressed both collective and unique cognitive aid preferences before trial
      completion. Trial phase results revealed that task completion accuracy did not
      alter substantially between trials; however, personal preferences and perceived
      usefulness of trialled cognitive aid systems appeared to impact support
      implementation and effectiveness. Themes emerged from post-trial interview
      relating to the (a) necessity for differing functions of individual systems and
      (b) importance of trialling devices prior to selection. CONCLUSIONS: Results
      emphasize the necessity of person-centred approaches to treatment due to the
      variability of performance accuracy and system preferences. The cognitive aid
      selection and implementation intervention protocol piloted in this study appears
      beneficial for understanding unique strengths and challenges for college students
      following mTBI and may be useful for clinicians working with individuals with
      mTBI. Implications for rehabilitation College-aged students with mild traumatic
      brain injury report unique preferences for no- and high-tech cognitive aids;
      however, similar patterns emerge relating to preferred system characteristics.
      Facilitating several trial periods prior to selection and implementation of
      external cognitive supports for individuals with mild traumatic brain injury is
      essential given the preference changes that occur post-trial. Implementing a
      three-phase external cognitive aid selection process appears beneficial for young
      adults with mild brain injuries.

PMID- 29350085
TI  - Divergent Classification Methods of Post-Concussion Syndrome after Mild Traumatic
      Brain Injury: Prevalence Rates, Risk Factors, and Functional Outcome.
AB  - Mild traumatic brain injury (mTBI) is a common diagnosis and approximately one
      third of mTBI patients experience a variety of cognitive, emotional,
      psychosocial, and behavioral post-concussion symptoms. When a cluster of these
      symptoms persists for more than 3 months they are often classified as post
      concussion syndrome (PCS). The objective of this study was to determine
      prevalence rates, risk factors, and functional outcome associated with PCS 6
      months after mTBI, applying divergent classification methods. Follow-up
      questionnaires at 6 months after mTBI included the Rivermead Post-Concussion
      Symptoms Questionnaire (RPQ) and the Glasgow Outcome Scale Extended (GOSE). The
      RPQ was analyzed according to different classification methods: the mapped
      International Classification of Diseases, 10th revision (ICD-10)/Diagnostic and
      Statistical Manual of Mental Disorders, 4th edition (DSM-IV), the RPQ total
      score, the RPQ3 and the three-factor model using two different cutoff points
      (mild or worse and moderate or worse). Our results from a sample of 731 mTBI
      patients showed that prevalence rates of PCS ranged from 11.4% to 38.7% using
      divergent classification methods. According to all eight methods, 6.3% (n = 46)
      of mTBI patients experienced PCS. Applying the divergent classification methods
      resulted in a different set of predictors being statistically significantly
      associated with PCS, and a different percentage of overlap with functional
      impairment, measured with the GOSE. In conclusion, depending on the
      classification method and rating score used, prevalence rates of PCS deviated
      considerably. For future research, consensus regarding the diagnostic criteria
      for PCS and the analysis of the RPQ should be reached, to enhance comparability
      of studies regarding PCS after mTBI.

PMID- 29350086
TI  - Hematoma clearance as a therapeutic target in intracerebral hemorrhage: From
      macro to micro.
AB  - Despite the absence of an intervention shown to improve outcomes in intracerebral
      hemorrhage, preclinical work has led to a greater understanding of the pathologic
      pathways of brain injury. Methods targeting hematoma clearance through both
      macroscopic (surgical) and microscopic (endogenous phagocytosis) means are
      currently under investigation, with multiple clinical trials ongoing. Macroscopic
      methods for removal involve both catheter- and endoscope-based therapies to
      remove the hematoma through minimally invasive surgery. Microscopic methods
      targeting hematoma clearance involve augmenting endogenous clearance pathways for
      red blood cells and altering the balance between phagocytosis and red blood cell
      lysis with the release of potentially harmful constituents (e.g. hemoglobin and
      iron) into the extracellular space.

PMID- 29350087
TI  - Segmentation of tongue shapes during vowel production in magnetic resonance
      images based on statistical modelling.
AB  - Quantification of the anatomic and functional aspects of the tongue is pertinent
      to analyse the mechanisms involved in speech production. Speech requires dynamic
      and complex articulation of the vocal tract organs, and the tongue is one of the
      main articulators during speech production. Magnetic resonance imaging has been
      widely used in speech-related studies. Moreover, the segmentation of such images
      of speech organs is required to extract reliable statistical data. However,
      standard solutions to analyse a large set of articulatory images have not yet
      been established. Therefore, this article presents an approach to segment the
      tongue in two-dimensional magnetic resonance images and statistically model the
      segmented tongue shapes. The proposed approach assesses the articulator
      morphology based on an active shape model, which captures the shape variability
      of the tongue during speech production. To validate this new approach, a dataset
      of mid-sagittal magnetic resonance images acquired from four subjects was used,
      and key aspects of the shape of the tongue during the vocal production of
      relevant European Portuguese vowels were evaluated.

PMID- 29350088
TI  - The use of synthetic ligaments in the design of an enhanced stability total knee
      joint replacement.
AB  - Current total knee replacement designs work to address clinically desired knee
      stability and range of motion through a balance of retained anatomy and added
      implant geometry. However, simplified implant geometries such as bearing
      surfaces, posts, and cams are often used to replace complex ligamentous
      constraints that are sacrificed during most total knee replacement procedures.
      This article evaluates a novel total knee replacement design that incorporates
      synthetic ligaments to enhance the stability of the total knee replacement
      system. It was hypothesized that by incorporating artificial cruciate ligaments
      into a total knee replacement design at specific locations and lengths, the
      stability of the total knee replacement could be significantly altered while
      maintaining active ranges of motion. The ligament attachment mechanisms used in
      the design were evaluated using a tensile test, and determined to have a safety
      factor of three with respect to expected ligamentous loading in vivo. Following
      initial computational modeling of possible ligament orientations, a physical
      prototype was constructed to verify the function of the design by performing
      anterior/posterior drawer tests under physiologic load. Synthetic ligament
      configurations were found to increase total knee replacement stability up to 94%
      compared to the no-ligament case, while maintaining total knee replacement
      flexion range of motion between 0 degrees  and 120 degrees , indicating that a
      total knee replacement that incorporates synthetic ligaments with calibrated
      location and lengths should be able to significantly enhance and control the
      kinematic performance of a total knee replacement system.

PMID- 29350089
TI  - A comparative analysis of internal bone remodelling concepts in a novel implant
      for direct skeletal attachment of limb prosthesis evaluation: A finite element
      analysis.
AB  - Nowadays, numerous internal bone remodelling concepts are under development, in
      order to estimate long-term functionality of implants by evaluating the intensity
      of stress-shielding effect. This effect is also analysed for the implants for
      direct skeletal attachment, considered as a better exoprosthesis fixation method
      than prosthetic sockets. Most of bone remodelling approaches are based on basic
      concepts, differing with certain assumptions, which may affect the accuracy of
      the results. This article compares commonly used internal bone remodelling
      concepts and evaluates the functionality of the proposed Limb Prosthesis
      Osseointegrated Fixation System for direct skeletal attachment of limb prosthesis
      in comparison with two currently available implants: the Intraosseous
      Transcutaneous Amputation Prosthesis and the Osseointegrated Prostheses for the
      Rehabilitation of Amputees. Three concepts were chosen: without and with lazy
      zone and with the use of quadratic formula which considers bone overloading.
      Therefore, three finite element models were created with identical femur
      implanted with each of analysed implants. The implants were loaded with loads
      that refer to two stages of gait cycle (heel strike and toe-off). The analysed
      concepts have given similar results, allowing to assume that each of them can be
      successfully used to estimate internal bone remodelling around analysed implants
      for direct skeletal attachment of limb prosthesis. The results also present
      higher functionality of the proposed implant for direct skeletal attachment of
      limb prosthesis due to a significant reduction in stress-shielding in the
      analysed areas around implant in comparison with the Intraosseous Transcutaneous
      Amputation Prosthesis and the Osseointegrated Prostheses for the Rehabilitation
      of Amputees. It suggests that the proposed design is a better alternative to the
      currently used solutions.

PMID- 29350090
TI  - Demographic determinants and outcome of in vitro fertilization (IVF) services in
      Saudi Arabia.
AB  - Objectives To assess the demographic characteristics and outcomes of couples
      undergoing in vitro fertilisation (IVF) treatment at a private hospital in Al
      Qassim district, Saudi Arabia. Methods For this retrospective study, information
      was extracted from the hospital electronic database and IVF unit medical records.
      Results 2259 couples underwent 2703 IVF/ICSI cycles during 2014 to 2016. The
      utilization rate was approximately 1000 cycle per million of inhabitants. Mean
      ages +/- standard deviation (SD) for women and men were 32.9 +/- 5.7 and 39.2 +/-
      7.4 years, respectively. More couples were diagnosed with secondary infertility
      (55.2%) than primary infertility (44.8%). Male factor was the commonest single
      indication for IVF (36.2%). Mean +/- SD infertility duration was 4.70 +/- 4.03
      years. Overall, 949 couples had a successful pregnancy. Age-specific pregnancy
      rates (PR) were highest for women <35 years (39.8%) and lowest for women >40
      years (11.6%). Male age and infertility duration had no effect on PR but sperm
      source (fresh vs. frozen) and female age had significant impacts. However, fresh
      sperm was used in 90.6% cycles whereas frozen sperm was used in 9.4% cycles.
      Conclusions IVF treatment outcomes in the Al Qassim district are within the
      boundaries of average international success rates. Infertile couples seeking IVF
      services should be counselled with regard to important prognostic factors.

PMID- 29350091
TI  - Stent-assisted coiling of cerebral aneurysms with the Neuroform Atlas stent.
AB  - Objectives The Neuroform Atlas stent (AS) is the smallest intracranial stent with
      an open-cell design. This study reports the first clinical experience with AS.
      Methods All intracranial aneurysms treated by stent-assisted coiling using a
      single AS in a single institution were retrospectively evaluated. Patient
      demographics, aneurysm characteristics, angles between the parent artery and
      stented branch, technical success, and clinical and angiographic follow-up were
      analyzed. Results Fifty-five consecutive aneurysms treated with AS-assisted
      coiling were included. Of these, 69.1% were located distal to the circle of
      Willis. Technical success rate was 100%. The mean diameters of proximal and
      distal parent arteries were 2.62 mm (range 1.5-4.4) and 1.8 mm (range 0.8-3.5),
      respectively. Except for a minor stroke in a patient who completely discontinued
      antiplatelet therapy on postoperative day 4, there were no clinical events with
      permanent sequelae, and 94.1% of patients had Raymond-Roy score of 1 or 2
      aneurysmal occlusion at a mean follow-up duration of 7.9 months. Although the
      angle between the parent artery and the stented branch increased significantly (
      p < 0.001) with time, the angular change at follow-up was only 16.45 +/- 11.03
      degrees and was inversely correlated both with preoperative angle and the
      diameter of the distal parent artery ( r = -0.465 and r = -0.433, respectively, p
      = 0.004 for both). Conclusion AS-assisted coiling was associated with a favorable
      early clinical outcome and angiographic results in this series. This stent can be
      used for distally located aneurysms and results in minimal alteration of the
      arterial anatomy.

PMID- 29350092
TI  - Focus on the target: Angiographic features of the fistulous point and prognosis
      of transvenous embolization of cavernous sinus dural arteriovenous fistula.
AB  - Background and purpose Transvenous embolization (TVE) is widely utilized as an
      effective and safe treatment option for cavernous sinus dural arteriovenous
      fistula (CS-dAVF); however, detecting the exact location of the fistula is
      challenging. The present study identified the angiographic features of the
      fistulous point and evaluated the match with the microcatheter tip and fistulous
      point. Materials and methods An analysis cohort of 45 consecutive patients with
      CS-dAVF treated by TVE was analyzed retrospectively. The patients were divided
      into two groups, 22 matches and 23 mismatches, according to whether the fistulous
      point and the microcatheter tip were in the same compartment of the cavernous
      sinus (CS). The angiographic findings, the location of the fistulas, the position
      of the microcatheter tips, the volume of embolic materials, complications, and
      outcomes were assessed. Results Several angiographic features defined the
      fistulous points, such as the early opacified area, jellyfish-like sign, changes
      in the density of the contrast medium, the juncture of different arterial supply,
      enlarged feeders, and hand-injection angiograms. The fistulas were primarily in
      the posterosuperior portion of the CS (80%) and medial side (73.3%) according to
      the internal carotid artery. Both groups achieved effective TVE; the matched
      group required less embolic material than the mismatched group ( p = 0.024). The
      patients with cranial nerve dysfunction (CND) required more embolic materials
      than others ( p = 0.032). Conclusion The fistulous point in most of the CS-dAVFs
      could be isolated by careful analysis of the angiography images. The matching of
      the microcatheter tip and fistulous point in the same compartment of CS can
      reduce the dosage of embolic materials, and a low volume of embolic materials
      might cause fewer CND complications.

PMID- 29350093
TI  - Thiobarbituric acid-reactive substances relate to arterial stiffness and blood
      pressure in 6 to 8-year-old boys stratified by maternal risk.
AB  - Early cardiovascular disease (CVD) onset can be inflicted by familial
      cardiovascular and lifestyle risk factors. We aimed to compare phenotypic
      characteristics and explore associations between oxidative stress and vascular
      function in boys stratified by maternal cardiovascular and lifestyle risk. We
      included 40 Black and 41 White boys (ages 6-8 years), along with the biological
      mother of each child. The study population was divided into two groups
      (nonmaternal risk vs. maternal risk) according to maternal risk predetermined by
      their selfreported cardiovascular and lifestyle risk factors. Pulse wave velocity
      (PWV) was measured at various sites and blood pressures were recorded. Urine
      samples were collected for analyses of thiobarbituric acid-reactive substances
      (TBARS), 8-hydroxy-2-deoxy guanosine (8-OHdG), albumin, and creatinine. Higher
      levels of urinary albumin to creatinine ratio (uACR) were found in the maternal
      risk group compared to the nonmaternal risk group (p = .038). Multiple regression
      analysis in the maternal risk group revealed diastolic blood pressure (R2 =
      0.159; beta = 0.293; p = .050), carotid femoral PWV (R2 = 0.158; beta = 0.297; p
      = .038) and carotid dorsalis pedis PWV (adj R2 = 0.322; beta = 0.505; p < .001)
      to be positively associated with TBARS, while an inverse association of uACR (R2
      = 0.161; beta = -0.261; p = .046) with TBARS was observed. Also, in the maternal
      risk group, independent associations of DBP (R2 = 0.273; beta = 0.289; p = .040)
      and uACR (R2 = 0.283; beta = 0.268; p = .027) with 8-OHdG were indicated. In
      boys, as young as 6 years of age, oxidative stress related to arterial stiffness
      and diastolic blood pressure was observed. This association was only evident in
      boys with linked maternal lifestyle and cardiovascular risk factors, suggesting
      potential family-related early onset of cardiovascular risk.

PMID- 29350095
TI  - The Bandwidth of Diagnostic Horizontal Structure for Face Identification.
AB  - Horizontally oriented spatial frequency components are a diagnostic source of
      face identity information, and sensitivity to this information predicts upright
      identification accuracy and the magnitude of the face-inversion effect. However,
      the bandwidth at which this information is conveyed, and the extent to which
      human tuning matches this distribution of information, has yet to be
      characterized. We designed a 10-alternative forced choice face identification
      task in which upright or inverted faces were filtered to retain horizontal or
      vertical structure. We systematically varied the bandwidth of these filters in 10
      degrees  steps and replaced the orientation components that were removed from the
      target face with components from the average of all possible faces. This
      manipulation created patterns that looked like faces but contained diagnostic
      information in orientation bands unknown to the observer on any given trial.
      Further, we quantified human performance relative to the actual information
      content of our face stimuli using an ideal observer with perfect knowledge of the
      diagnostic band. We found that the most diagnostic information for face
      identification is conveyed by a narrow band of orientations along the horizontal
      meridian, whereas human observers use information from a wide range of
      orientations.

PMID- 29350094
TI  - Medium-chain acyl-CoA dehydrogenase deficiency: Two novel ACADM mutations
      identified in a retrospective screening.
AB  - Objective The aim of this study was to determine whether an expanded newborn
      screening programme, which is not yet available in Slovenia, would have detected
      the first two patients with medium-chain acyl-CoA dehydrogenase (MCAD) deficiency
      in the country. Two novel ACADM mutations are also described. Methods Both
      patients were diagnosed clinically; follow-up involved analysis of organic acids
      in urine, acylcarnitines in dried blood spots, and genetic analysis of ACADM. Cut
      off values of acylcarnitines in newborns were established using analysis of
      10,000 newborns in a pilot screening study. Results In both patients, analysis of
      the organic acids in urine showed a possible beta-oxidation defect, while the
      specific elevation of acylcarnitines confirmed MCAD deficiency. Subsequent
      genetic analysis confirmed the diagnosis; both patients were compound
      heterozygotes, each with one novel mutation (c.861 + 2T > C and c.527_533del).
      The results from a retrospective analysis of newborn screening cards clearly
      showed major elevations of MCAD-specific acylcarnitines in the patients.
      Conclusions An expanded newborn screening programme would be beneficial because
      it would have detected MCAD deficiency in both patients before the development of
      clinical signs. Our study also provides one of the first descriptions of ACADM
      mutations in Southeast Europe.

PMID- 29350096
TI  - alpha-Tocopherol protected against cobalt nanoparticles and cocl2 induced
      cytotoxicity and inflammation in Balb/3T3 cells.
AB  - CONTEXT: Currently, tissue damage induced by cobalt nanoparticles (CoNPs) and
      cobalt ions (Co2+) are the most serious adverse effect in the patients with metal
      on-metal hip prostheses. Therefore, an urgent need exists for the identification
      of the mechanisms and the development of therapeutic strategies to limit it.
      OBJECTIVE: We aimed to explore the mechanisms of cytotoxicity of CoNPs and Co2+
      and developed strategies to reduce this cytotoxicity with alpha-tocopherol
      treatment. METHODS: To evaluate the protective effect of alpha-tocopherol,
      Balb/3T3 cells were pretreated with 10 MUM alpha-tocopherol for 24 h. The cells
      were then exposed to different concentrations of CoNPs and Co2+ for 12 h, 24 h
      and 48 h. The cell viabilities, reactive oxygen species (ROS), inflammatory
      cytokines and MAP kinase (MAPK) levels were measured. RESULTS: CoNPs and Co2+ can
      induce the increase of ROS and inflammatory cytokines in Balb/3T3 cells, such as
      tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta) and
      interleukin-6 (IL-6). However, alpha-tocopherol pretreatment can significantly
      prevent cytotoxicity induced by CoNPs and Co2+, decrease ROS production and
      decrease levels of inflammatory cytokines in Balb/3T3 cells. Additionally, MAPK
      pathway may be involved in the protection of alpha-tocopherol against
      cytotoxicity induced by CoNPs and Co2+ in vitro. CONCLUSIONS: Our results provide
      new insights into the potential therapeutic use of alpha-tocopherol in the
      prevention and treatment of various oxidative- or inflammatory stress-related
      inflammation and injuries.

PMID- 29350097
TI  - Paternal Perinatal Depression Assessed by the Edinburgh Postnatal Depression
      Scale and the Gotland Male Depression Scale: Prevalence and Possible Risk
      Factors.
AB  - Several studies have used the Edinburgh Postnatal Depression Scale (EPDS),
      developed to screen new mothers, also for new fathers. This study aimed to
      further contribute to this knowledge by comparing assessment of possible
      depression in fathers and associated demographic factors by the EPDS and the
      Gotland Male Depression Scale (GMDS), developed for "male" depression screening.
      The study compared EPDS score >=10 and >=12, corresponding to minor and major
      depression, respectively, in relation to GMDS score >=13. At 3-6 months after
      child birth, a questionnaire was sent to 8,011 fathers of whom 3,656 (46%)
      responded. The detection of possibly depressed fathers by EPDS was 8.1% at score
      >=12, comparable to the 8.6% detected by the GMDS. At score >=10, the proportion
      detected by EPDS increased to 13.3%. Associations with possible risk factors were
      analyzed for fathers detected by one or both scales. A low income was associated
      with depression in all groups. Fathers detected by EPDS alone were at higher risk
      if they had three or more children, or lower education. Fathers detected by EPDS
      alone at score >=10, or by both scales at EPDS score >=12, more often were born
      in a foreign country. Seemingly, the EPDS and the GMDS are associated with
      different demographic risk factors. The EPDS score appears critical since 5% of
      possibly depressed fathers are excluded at EPDS cutoff 12. These results suggest
      that neither scale alone is sufficient for depression screening in new fathers,
      and that the decision of EPDS cutoff is crucial.

PMID- 29350098
TI  - Commentary to 18F-GP1, a Novel PET Tracer Designed for High-Sensitivity, Low
      Background Detection of Thrombi: Imaging Activated Platelets in Clots-Are We
      Getting There?
AB  - Thrombus formation can lead to heart attacks, stroke and pulmonary embolism,
      which are major causes of mortality. Current standard diagnostic imaging methods
      detect anatomic abnormalities such as vascular flow impairment but have
      limitations. By using a targeted molecular imaging approach critical components
      of a pathology can be selectively visualized and exploited for an improved
      diagnosis and patient management. The GPIIb/IIIa receptor is abundantly and
      specifically exposed on activated platelets and is the key receptor in thrombus
      formation. This commentary describes the current status of GPIIb/IIIa-based PET
      imaging approaches with a focus on the recently published preclinical data of the
      small-molecule PET tracer 18F-GP1. Areas of future research and potential
      clinical applications are discussed that may lead to an improved detection of
      critical thromboembolic events and an optimization of available antithrombotic
      therapies by tracking activated platelets.

PMID- 29350099
TI  - Does shortening the pitch make junior cricketers bowl better?
AB  - In order to get bounce and movement seam bowlers need to bowl the ball "into" the
      pitch. Standard deliveries by elite players are typically projected at around 7
      degrees  below horizontal. In contrast, young players currently often need to
      release the ball almost horizontally in an effort to get the ball to bounce close
      enough to the batter. We anticipated that shortening the pitch could be a simple
      way to help young bowlers to release the ball at a better angle and with more
      consistency. Twenty county or best in club age group under 10 and under 11 seam
      bowlers were analysed bowling indoors on two different pitch lengths. They were
      found to project the ball on average 3.4 degrees  further below horizontal on a
      16 yard pitch compared with a 19 yard pitch, while ball speed and position at
      release changed negligibly. Pitch length did not affect the consistency of the
      release parameters. The shorter pitch led to a ball release angle closer to that
      of elite bowlers without changing release speed, and this should enable players
      to achieve greater success and develop more variety in their bowling.

PMID- 29350100
TI  - Transorbital Doppler with carotid siphon monitoring detects right-to-left shunt
      effectively.
AB  - Background Transtemporal Doppler (TTD) with middle cerebral artery (MCA) is
      widely used for right-to-left shunt (RLS) detection. However, an alternative
      method for patients without suitable temporal bone windows should be established.
      The present study prospectively evaluated the effectiveness of transorbital
      Doppler (TOD) with carotid siphon (CS) monitoring in detecting RLS. Methods A
      total of 357 subjects with sufficient temporal bone windows underwent
      simultaneous TTD with MCA and TOD with CS. After injection of microbubbles, the
      numbers of artificial high-intensity signals were recorded at rest and after
      Valsalva maneuver. Results TOD with CS detected RLS in 146 patients. Sensitivity
      was 97.1%, specificity 95%, positive predictive value 92.5%, and negative
      predictive value 98.1%. The total positive rates for RLS detection by CS (40.9%)
      and MCA (37.8%) monitoring were comparable without significant difference, but
      TOD with CS detected significantly more grade 2 and 3 RLS than TTD with MCA (p =
      0.001). The RLS rates of cryptogenic stroke patients was significantly higher
      than that of healthy controls, and RLS in cryptogenic stroke was remarkably
      higher than that in transient ischemia attack patients (p < 0.05). TOD with CS
      examined significantly more grade 2 and 3 RLSs than the MCA approach in the
      cryptogenic stroke patients (p = 0.037). Conclusion TOD with CS monitoring is
      able to detect RLS effectively in different populations including healthy
      subjects, cryptogenic stroke, transient ischemia attack, and migraine patients.
      In comparing to the TTD with MCA approach, TOD with CS monitoring could detect
      comparable rate of RLS, but more high grades of RLS.

PMID- 29350101
TI  - Biomimetic Composite Scaffold Containing Small Intestinal Submucosa and
      Mesoporous Bioactive Glass Exhibits High Osteogenic and Angiogenic Capacity.
AB  - Biomaterials with excellent osteogenic and angiogenic activities are desirable to
      repair massive bone defects. Decellularized matrix from porcine small intestinal
      submucosa (SIS) has attracted particular attention for tissue regeneration
      because it has strong angiogenic effects and retains plentiful bioactive
      components. However, it has inferior osteoinductivity and osteoconductivity. In
      this study, we developed porous composite of SIS combined with mesoporous
      bioactive glass (SIS/MBG) with the goal of improving the mechanical and
      biological properties. SIS/MBG scaffolds showed uniform interconnected macropores
      (~150 MUm), high porosity (~76%), and enhanced compressive strength (~0.87 MPa).
      The proliferation and osteogenic gene expression (Runx2, ALP, Ocn, and Col
      Ialpha) of rat bone marrow stromal cells (rBMSCs) as well as the proliferation,
      angiogenic gene expression (VEGF, bFGF, and KDR), and tube formation capacity of
      human umbilical vein endothelial cells (HUVECs) in SIS/MBG scaffolds were
      significantly upregulated compared with nonmesoporous bioactive glass (BG)
      modified SIS (SIS/BG) and SIS-only scaffolds. Western blot analysis revealed that
      SIS/MBG induced rBMSCs to osteogenic differentiation through the activation of
      Wnt/beta-Catenin signaling pathway, and SIS/MBG enhanced angiogenic activity of
      HUVEC through the activation of PI3k/Akt pathways. The in vivo results
      demonstrated that SIS/MBG scaffolds significantly enhanced new bone formation and
      neovascularization simultaneously in critical-sized rat calvarial defects as
      compared with SIS/BG and SIS. Collectively, the osteostimulative and
      angiostimulative biomimetic composite scaffold SIS/MBG represents an exciting
      biomaterial option for bone regeneration.

PMID- 29350102
TI  - Preoperative Clinical and Sonographic Predictors for Lateral Cervical Lymph Node
      Metastases in Sporadic Medullary Thyroid Carcinoma.
AB  - BACKGROUND: Total thyroidectomy and cervical lymph node (LN) dissection is
      generally recommended in patients with medullary thyroid carcinoma (MTC).
      However, there is no clear evidence for whom to perform prophylactic lateral neck
      dissection in MTC patients without evident lateral cervical lymph node (LCLN)
      metastasis in preoperative images. This study evaluated the preoperative features
      for predicting the LCLN metastasis of MTC. METHODS: The study included 26 MTC
      patients with LCLN metastasis at initial surgery (N1b group) and 47 MTC patients
      without any LN metastasis or recurrence of disease (N0-NED group). The
      association between LCLN metastasis and preoperative clinical and sonographic
      characteristics (size, location, solid component, shape, margin, echogenicity,
      calcification, and subcapsular location of the tumor) were evaluated. RESULTS:
      There were no significant differences in age and sex between the N1b and N0-NED
      groups. Preoperative serum levels of calcitonin >65 pg/mL were associated with
      LCLN metastasis (p < 0.001). In preoperative neck ultrasonography (US), patients
      in the N1b group were more commonly found with a larger tumor (>1.5 cm) of
      irregular shape with a spiculated margin and a subcapsular location than those in
      the N0-NED group (p = 0.029, p < 0.001, p < 0.001, and p < 0.001, respectively).
      Increases in the number of these LCLN metastasis-related features were
      significantly associated with higher risk for LCLN metastasis (p < 0.001). The
      presence of two or more predictors was an appropriate cutoff point for predicting
      LCLN metastasis of MTC with 73.1% sensitivity and 91.5% specificity. CONCLUSIONS:
      MTC tumors with high preoperative calcitonin levels (>65 pg/mL), larger size
      (>1.5 cm), irregular shape, spiculated margins, and subcapsular locations in the
      neck US are at higher risk for LCLN metastasis. MTC patents with fewer than two
      predictors might be suitable for treatment without prophylactic LCLN dissection.

PMID- 29350103
TI  - Society for the History of Alchemy and Chemistry Award Scheme 2018.

PMID- 29350104
TI  - The importance of perfusion index monitoring in evaluating the efficacy of
      stellate ganglion blockage treatment in Raynaud's disease.
AB  - Stellate ganglion blockage (SGB) is a method used for treating Raynaud's
      phenomenon (RP). This study primarily aimed to determine whether the perfusion
      index (PI) can be used an alternative to Horner's signs in evaluating the
      efficacy of SGB in patients diagnosed with RP. In a total of 40 patients, aged 18
      65 years and diagnosed with primary RP, SGB was applied for 5 days on the same
      side with the 2-finger method, using 6 mL of 5% levobupivacaine at the 7th
      cervical vertebra level. The PI values were recorded from the distal end of the
      2nd finger of the upper extremity on the side applied with the block at baseline
      and at 5, 15, 30, 60 and 120 min. The onset time of Horner findings was recorded.
      The PI values and visual analogue scale (VAS) pain scores were recorded pre
      treatment and after 2 weeks.When the PI values of the 40 patients were examined,
      a 62.7% increase was observed from baseline to the first session at 5 min (p <
      0.05). When all sessions were evaluated, a statistically significant increase was
      determined in the PI values measured at 5, 15, 30, 60 and 120 min compared with
      the baseline PI values. There was a statistically significant decrease in the
      post-treatment VAS pain scores and a statistically significant increase in the
      post-treatment PI values (p < 0.05). By eliminating peripheral vasospasm with the
      application of SGB in patients with RP, the distal artery blood flow and PI are
      increased. PI measurement is a more objective method and therefore could be used
      as an alternative to Horner findings in evaluating the success of SGB. PI is a
      non-invasive and simple measurement and also an earlier indicator in evaluating
      the success of SGB than Horner's signs.

PMID- 29350105
TI  - Persistent modification of cognitive control through attention training.
AB  - An important aspect of cognitive control is to direct attention towards relevant
      information and away from distracting information. This attentional modulation is
      at the core of several influential frameworks, but its trainability and
      generalisability remain unclear. To address this issue, two groups of subjects
      were invited to the lab on three consecutive days. On Day 2, they performed an
      arrow priming task which trained them to adopt an attentional bias towards (prime
      attended group) or away from (prime-diverted group) a potentially conflicting
      prime. Direct generalisation of the attention training was measured by assessing
      task performance on the same task without the attentional manipulation directly
      after training (Day 2) and the next day (Day 3), and comparing it to baseline
      (Day 1). Performance on this direct transfer task showed a difference in
      attentional modulation between groups directly after training that persisted the
      next day. No cross-task generalisation was found to two other tasks that were
      closely or more remotely related to the trained task. Together, these results are
      in accordance with cognitive control frameworks that limit attentional modulation
      to the specific features of the trained task.

PMID- 29350106
TI  - Cross-cultural differences in adult Theory of Mind abilities: A comparison of
      native-English speakers and native-Chinese speakers on the Self/Other
      Differentiation task.
AB  - Theory of Mind (ToM) refers to the ability to compute and attribute mental states
      to ourselves and other people. It is currently unclear whether ToM abilities are
      universal or whether they can be culturally influenced. To address this question,
      this research explored potential differences in engagement of ToM processes
      between two different cultures, Western (individualist) and Chinese
      (collectivist), using a sample of healthy adults. Participants completed a
      computerised false-belief task, in which they attributed beliefs to either
      themselves or another person, in a matched design, allowing direct comparison
      between "Self"- and "Other"-oriented conditions. Results revealed that both
      native-English speakers and native-Chinese individuals responded significantly
      faster to self-oriented than other-oriented questions. Results also showed that
      when a trial required a "perspective-shift," participants from both cultures were
      slower to shift from Self-to-Other than from Other-to-Self. Results indicate that
      despite differences in collectivism scores, culture does not influence task
      performance, with similar results found for both Western and non-Western
      participants, suggesting core and potentially universal similarities in the ToM
      mechanism across these two cultures.

PMID- 29350107
TI  - The effects of ethnicity, musicianship, and tone language experience on pitch
      perception.
AB  - Language and music are intertwined: music training can facilitate language
      abilities, and language experiences can also help with some music tasks. Possible
      language-music transfer effects are explored in two experiments in this study. In
      Experiment 1, we tested native Mandarin, Korean, and English speakers on a pitch
      discrimination task with two types of sounds: speech sounds and fundamental
      frequency (F0) patterns derived from speech sounds. To control for factors that
      might influence participants' performance, we included cognitive ability tasks
      testing memory and intelligence. In addition, two music skill tasks were used to
      examine general transfer effects from language to music. Prior studies showing
      that tone language speakers have an advantage on pitch tasks have been taken as
      support for three alternative hypotheses: specific transfer effects, general
      transfer effects, and an ethnicity effect. In Experiment 1, musicians
      outperformed non-musicians on both speech and F0 sounds, suggesting a music-to
      language transfer effect. Korean and Mandarin speakers performed similarly, and
      they both outperformed English speakers, providing some evidence for an ethnicity
      effect. Alternatively, this could be due to population selection bias. In
      Experiment 2, we recruited Chinese Americans approximating the native English
      speakers' language background to further test the ethnicity effect. Chinese
      Americans, regardless of their tone language experiences, performed similarly to
      their non-Asian American counterparts in all tasks. Therefore, although this
      study provides additional evidence of transfer effects across music and language,
      it casts doubt on the contribution of ethnicity to differences observed in pitch
      perception and general music abilities.

PMID- 29350108
TI  - The role of stimulus comparison in animal perceptual learning: Effects of a
      distractor placement.
AB  - Research on perceptual learning shows that the way stimuli are presented leads to
      different outcomes. The intermixed/blocked (I/B) effect is one of these outcomes,
      and different mechanisms have been proposed to explain it. In human research, it
      seems that comparison between stimuli is important, and the placement of a
      distractor between the pre-exposed stimuli interferes with the effect. Results
      from animal research are usually interpreted in different terms because the type
      of procedure normally used in animal perceptual learning does not favour
      comparison. In our experiments, we explore the possibility that a distractor
      placed between the to-be-discriminated stimuli may interfere with the perceptual
      learning process in rats. In Experiment 1, two flavoured solutions are presented
      in an I/B fashion, with a short time lapse between them to favour comparison,
      showing the typical I/B effect. In Experiment 2, we introduced a distractor in
      between the solutions, abolishing this effect. Experiment 3 further replicates
      this by comparing two intermixed groups with or without distractor. The results
      replicate the findings from human research, suggesting that comparison also plays
      an important role in animal perceptual learning.

PMID- 29350110
TI  - Construct validity of the resistance training skills battery in children aged 7
      10 years.
AB  - The current study sought to examine the construct validity of the Resistance
      Training Skills Battery for Children (RTSBc), a movement screen purported to
      assess resistance training skill in children. Children aged 7-10 years (n = 27,
      21 males, 6 females) undertook measures of resistance training skill via the
      RTSBc, motor competence and muscular fitness. Using a median split for RTSBc
      scores, children were categorised as high or low resistance training competence.
      Univariate ANCOVAs, controlling for maturation, were used to examine whether
      measures of muscular fitness and motor competence scores differed as a function
      of RTSBc competence. Children who were classified as high for resistance training
      competence had significantly better motor competence (P = .001) and significantly
      faster 10 m sprint speed (P = .001). However, medicine ball throw and standing
      long jump scores as well as peak and average isokinetic muscle strength did not
      differ as a function of RTSBc (P > 0.05). In all cases maturation was significant
      as a covariate. This study is the first to demonstrate construct validity of the
      RTSBc as a measure of general motor competence and sprint speed, but not
      strength, in children aged 7-10 years.

PMID- 29350109
TI  - Tertiary Care Experience of Sorafenib in the Treatment of Progressive Radioiodine
      Refractory Differentiated Thyroid Carcinoma: A Korean Multicenter Study.
AB  - BACKGROUND: Sorafenib, a multi-kinase inhibitor, is approved for the treatment of
      patients with radioactive iodine (RAI)-refractory differentiated thyroid cancer
      (DTC). This study evaluated the efficacy and safety of sorafenib in real-world
      clinical practice and compared the results to those of the DECISION trial. The
      clinical features associated with better clinical outcomes after sorafenib
      treatment were also evaluated. METHODS: This multicenter, retrospective cohort
      study evaluated 98 patients with progressive RAI-refractory DTC who were treated
      with sorafenib in six tertiary hospitals in Korea. The primary objective was the
      progression-free survival (PFS) according to Response Evaluation Criteria In
      Solid Tumors v1.1. Overall survival, response rate (defined as the best objective
      response according to Response Evaluation Criteria In Solid Tumors v1.1), and
      safety were also evaluated. RESULTS: The median PFS was 9.7 months; median
      overall survival was not reached during follow-up. Partial responses and stable
      disease were achieved in 25 (25%) and 64 (65%) patients, respectively. Stable
      disease of >6 months was achieved in 41 (42%) patients. Subgroup analyses
      identified several prognostic indicators of a better PFS: absence of disease
      related symptoms (hazard ratio [HR] = 0.5; p = 0.041), lung-only metastasis (HR =
      0.4; p = 0.048), a daily maintenance dose >=600 mg (HR = 0.3; p = 0.005), and a
      thyroglobulin reduction >=60% (HR = 0.4; p = 0.012). The mean daily dose of
      sorafenib was 666 +/- 114 mg, and drug withdrawals due to adverse events (AEs)
      occurred in 13% of patients. AEs and serious AEs were reported in 93 (95%) and 40
      (41%) patients, respectively. The most frequent AE was hand-foot skin reaction
      (76%). CONCLUSIONS: The PFS of progressive RAI-refractory DTC patients treated
      with sorafenib was consistent with the findings of the DECISION trial. Disease
      related symptoms, lung-only metastasis, a daily maintenance dose, and
      thyroglobulin reduction were significantly associated with PFS. These results
      suggest that sorafenib is an effective treatment option for patients with
      progressive RAI-refractory DTC.

PMID- 29350111
TI  - Sustained viral suppression with co-administration of oxcarbazepine and
      dolutegravir.
AB  - Co-administration of dolutegravir and oxcarbazepine has been reported to reduce
      levels of dolutegravir and therefore is contraindicated due to insufficient data
      to make dosing recommendations. We present eight cases in which patients with
      human immunodeficiency virus (HIV) inadvertently received oxcarbazepine while
      concurrently receiving 50 mg of dolutegravir daily as part of their
      antiretroviral therapy. Upon further evaluation, lab results revealed that
      despite the risk of decreased levels of dolutegravir due to possible
      oxcarbazepine enzyme induction, patients maintained at or near virologic
      suppression (viral load <20 copies/ml). Suppression was maintained in patients
      virally suppressed prior to oxcarbazepine initiation as well as in patients
      receiving high doses of oxcarbazepine (>1200 mg). All patients self-reported
      complete adherence to oxcarbazepine and dolutegravir. Furthermore, careful review
      of additional patient medications suggested no other identifiable drug
      interactions that could have affected their antiretroviral therapy. This case
      series suggests that despite the well-documented drug interaction, concomitant
      administration of oxcarbazepine and dolutegravir in the clinical setting did not
      adversely affect viral suppression in patients with HIV.

PMID- 29350112
TI  - A comparison of HIV-risk behaviors between young black cisgender men who have sex
      with men and young black transgender women who have sex with men.
AB  - This study compared sexually transmitted infection (STI)-associated risks between
      young Black cisgender men who have sex with men (YBMSM) and young Black
      transwomen who have sex with men (YBTWSM). Comparisons pertained to: (1)
      prevalence of infections; (2) sexual risk; (3) partner-related risks; and (4)
      socioeconomic marginalization. YBMSM (n = 577) and YBTWSM (n = 32) were recruited
      from an STI clinic in the USA. Volunteers completed a computer-assisted self
      interview and medical records were abstracted for STI/HIV information.
      Significantly greater prevalence of pharyngeal Chlamydia ( P < .001) and
      pharyngeal gonorrhea ( P = .04) occurred among YBTWSM; however, both associations
      were moderated and only significant for HIV-uninfected volunteers. YBTWSM had
      more oral sex partners and more frequent engagement in oral sex. The number of
      new sex partners for anal receptive sex was greater in YBTWSM. YBTWSM were more
      likely to exchange sex for money/drugs ( P < .001), have sex with men recently in
      prison ( P < .001), who were "anonymous" ( P = .004), or who were "one night
      stands" ( P < .001). YBTWSM were more likely to depend on sex partners for money
      food, etc. ( P < .001), to miss meals due to lack of money ( P = .01), and to
      report having ever being incarcerated ( P = .009). Compared to cisgender YBMSM,
      YBTWSM experience multiple risk factors relative to the acquisition/transmission
      of STIs and HIV.

PMID- 29350113
TI  - Asymptomatic urethral lymphogranuloma venereum: a case report.
AB  - Since 2003, there has been a resurgence of lymphogranuloma venereum (LGV), a
      variant of Chlamydia trachomatis (CT), among men who have sex with men (MSM) in
      several urban areas of Europe and North America. LGV infection occurs most often
      at anal sites causing proctitis. Urethral and oropharyngeal infections are rare.
      In Quebec, LGV incidence has been increasing exponentially in recent years and
      the current guidelines support systematic LGV genotype testing among anorectal CT
      positive samples only. This case report describes a patient with a urethral LGV
      infection, remarkable due to its prolonged asymptomatic development prior to the
      manifestation of an inguinal bubo. Physicians should be vigilant of potential
      cases of LGV and forward CT-positive samples occurring among individuals with LGV
      risk factors for genotype testing.

PMID- 29350114
TI  - The influence of solid retention time on IFAS-MBR systems: analysis of system
      behavior.
AB  - A University of Cape Town Integrated Fixed-Film Activated Sludge Membrane
      Bioreactor (UCT-IFAS-MBR) pilot plant was operated at different values of the
      sludge retention time (SRT). Three SRTs were investigated at different durations:
      indefinitely, 30 and 15 days. The organic carbon, nitrogen and phosphorus
      removal, kinetic/stoichiometric parameters, membrane fouling tendency and sludge
      filtration properties were assessed. The findings showed that by decreasing the
      SRT, the pilot plant could maintain excellent carbon removal efficiencies
      throughout the experiments. In contrast, the biological carbon removal showed a
      slight nitrification and was slightly affected by the decrease of the SRT,
      showing high performance (approximately 91%, on average). Thus, the biofilm might
      have helped sustain the nitrification throughout the experiments. The average
      phosphorus removal performance increased slightly with a decrease in SRT,
      achieving the maximum efficiency (61.5%) at a SRT of 15 days. After a 30-day SRT,
      an increase in resistance due to pore blocking and a general worsening of the
      membrane filtration properties occurred.

PMID- 29350115
TI  - [Haemolysis: role of the direct antiglobulin test and eluate].
AB  - Haemolytic anaemia is the result of an abnormal breakdown of red blood cells. The
      direct antiglobulin test (DAT), also known as the direct Coombs test, can be used
      to determine the cause of the haemolysis. The DAT distinguishes between immune
      and non-immune causes of haemolysis. However, the DAT should not be used in
      screening for haemolysis. When the DAT is performed without an indication for in
      vivo haemolysis, there is a high risk of false-positive results. To increase the
      specificity of the DAT, the eluate can be tested to determine the specificity of
      the autoantibodies. In this article we present two cases of haemolytic anaemia in
      which the DAT gives further indication of the cause of haemolysis.

PMID- 29350116
TI  - [Upper abdominal pain after an elective aortic valve replacement].
AB  - A 69-year-old man came to our emergency department with nausea, vomiting and
      upper abdominal pain under the suspicion of an ileus. Four weeks before he had
      had an elective aortic valve replacement. The basal thoracic slides of the
      abdominal CT-scan revealed a significant amount of pericardial effusion, after
      which the patient was referred for emergency cardiac surgery. Abdominal
      complaints are rarely the primary symptoms of severe heart failure.

PMID- 29350117
TI  - [Treating poisoning; how do you choose the best type of gastrointestinal
      decontamination?]
AB  - - A new guideline: 'Intoxication: initial approach in the hospital' will be
      published this year. This guideline sets out the latest insights on
      gastrointestinal decontamination in intoxication; the advice is summarized in a
      flowchart.- The advice is to generally administer activated charcoal, unless
      there are indications that the toxin will not bind to activated charcoal or that
      the amount of toxin that the patient has ingested is too great; in these cases
      gastric lavage can be considered.- Activated charcoal can be administered up to 2
      hours after the ingestion of a toxic substance, unless there are contra
      indications. Multiple-dose activated charcoal in combination with a laxative can
      be administered in cases of overdose with toxins that use the enterohepatic
      circulation (such as theophylline, carbamazepine, quinine, dapsone and
      phenobarbital).- Gastric lavage should be limited to extremely serious
      intoxication, when the substance has been ingested less than 1-2 hours
      previously.- Whole-bowel irrigation should not be performed routinely but should
      be limited to ingestion of toxins with sustained release or enteric coating, or
      for toxins that do not bind to activated charcoal.

PMID- 29350118
TI  - [Online tool to prepare patient for colonoscopy; development and implementation
      of a patient-education app].
AB  - Optimal patient education prior to colonoscopy is essential for an optimal
      outcome of the procedure. Patients benefit from adequate information regarding
      laxatives, risks and alternatives, and must provide informed consent. The
      endoscopist also has to have access to patient data in advance of the procedure
      in order to carry out an adequate risk assessment for the use of sedation. Most
      centres in the Netherlands usually make use of a pre-endoscopy consultation to
      exchange this information, but here is now pressure on this practice because the
      number of colonoscopies is increasing rapidly as a result of the introduction of
      the national screening programme for colorectal cancer.

PMID- 29350119
TI  - [Medication-overuse headache].
AB  - - Medication-overuse headache is a highly prevalent disorder with a major impact
      on the quality of life.- Medication-overuse headache is defined as headache on >=
      15 days per month with overuse of acute headache medication for >= 3 months. We
      talk about overuse in case of intake of simple analgesics on >= 15 days per month
      or triptans or combinations of analgesics on >= 10 days per month.- The
      underlying type of headache is usually migraine or tension-type headache.- One of
      the possible underlying mechanisms of medication-overuse headache is changed
      sensitivity as a consequence of central sensitisation.- The initial treatment is
      detoxification of the headache medication. The preferred detoxification method is
      outpatient, abrupt withdrawal of all acute-headache medication and caffeine
      containing products. Essential for successful detoxification is education about
      the reasons for detoxification, the expected course and the subsequent treatment.

PMID- 29350120
TI  - [Continued development of drugs: the path of thioguanine].
AB  - Continued development of existing drugs ('drug rediscovery') may offer new
      therapeutic options and be cost-effective. Rediscovered drugs are commonly
      prescribed off-label, although licensing can be important to allow safe and
      controlled prescription of the drugs to patients. Licensing of a new indication
      for a generic drug, however, is a complicated process since there is no blueprint
      for this and there is little interest from the pharmaceutical industry due to an
      unattractive cost-recovery model. In this article, we illustrate the successful
      license-extension for thioguanine - initially developed in 1950 for leukaemia -
      as a new treatment for patients with inflammatory bowel disease.

PMID- 29350121
TI  - [A boy with involuntary movements].
AB  - A 12-year-old Dutch boy came to the paediatrician with involuntary movements of
      the right half of his body. He was diagnosed with Sydenham chorea as a
      consequence of acute rheumatic fever. Acute rheumatic fever is a rare disease in
      Western countries and should be recognised in time. Antibiotic prophylaxis is
      indicated in patients who have had acute rheumatic fever, at least until the age
      of 40.

PMID- 29350122
TI  - [An African boy with haematuria].
AB  - An 8-year-old, Senegalese boy presented with a history of painless macroscopic
      haematuria. The diagnosis schistosomiasis was made, based on the urine sediment
      that revealed eggs from the trematode parasite Schistosoma haematobium. The
      patient was treated with praziquantel and made a full recovery.

PMID- 29350123
TI  - [DoNTRuN a neurosurgical trainee network; network for the advancement of clinical
      research].
AB  - There is a lot of research into the effectiveness of interventions, but good
      evidence for many interventions is missing. This is very true of simple and
      frequently performed treatments. These interventions are often done by trainees
      in the course of their specialist training, and for this reason they are in a
      unique position to carry out research into them. There are far fewer high
      quality, multicentre clinical trials in the surgical specialisations than in any
      other specialisation. As trainee neurosurgeons, we are of the opinion that this
      can be improved upon. With the establishment of the Dutch Neurosurgical Trainee
      Research Network (DoNTRuN), a national network, we are aiming to initiate and
      carry out new clinical trials. This initiative, which is currently unique in the
      Netherlands, will not only enable us to set up multicentre clinical trials
      relatively simply, but will also educate trainees in the carrying out of thorough
      clinical research, an area neglected in the current training program.

PMID- 29350125
TI  - Current management: migraine headache.
AB  - Migraine varies in its frequency, severity, and impact; treatment should consider
      these variations and the patient's needs and goals. Migraine pharmacologic
      treatment may be acute (abortive) or preventive (prophylactic), and patients
      often require both. New medication devices are available or in development,
      including an intracutaneous, microneedle system of zolmitriptan and sumatriptan,
      and breath-powered powder sumatriptan intranasal treatment. Lasmiditan, a 5-HT1F
      receptor agonist, is in development for acute treatment, as are small molecule
      calcitonin gene-related peptide (CGRP) receptor antagonists (Gepants) for acute
      and preventive treatment. Antibodies to CGRP and its receptor are being developed
      for migraine prevention. All 4 treatments are effective and have, as of yet, no
      safety concerns.

PMID- 29350124
TI  - A dimensional approach to assessing psychiatric risk in adults born very preterm.
AB  - BACKGROUND: Individuals who were born very preterm have higher rates of
      psychiatric diagnoses compared with term-born controls; however, it remains
      unclear whether they also display increased sub-clinical psychiatric
      symptomatology. Hence, our objective was to utilize a dimensional approach to
      assess psychiatric symptomatology in adult life following very preterm birth.
      METHODS: We studied 152 adults who were born very preterm (before 33 weeks'
      gestation; gestational range 24-32 weeks) and 96 term-born controls.
      Participants' clinical profile was examined using the Comprehensive Assessment of
      At-Risk Mental States (CAARMS), a measure of sub-clinical symptomatology that
      yields seven subscales including general psychopathology, positive, negative,
      cognitive, behavioural, motor and emotional symptoms, in addition to a total
      psychopathology score. Intellectual abilities were examined using the Wechsler
      Abbreviated Scale of Intelligence. RESULTS: Between-group differences on the
      CAARMS showed elevated symptomatology in very preterm participants compared with
      controls in positive, negative, cognitive and behavioural symptoms. Total
      psychopathology scores were significantly correlated with IQ in the very preterm
      group only. In order to examine the characteristics of participants' clinical
      profile, a principal component analysis was conducted. This revealed two
      components, one reflecting a non-specific psychopathology dimension, and the
      other indicating a variance in symptomatology along a positive-to-negative
      symptom axis. K-means (k = 4) were used to further separate the study sample into
      clusters. Very preterm adults were more likely to belong to a high non-specific
      psychopathology cluster compared with controls.Conclusion and RelevanceVery
      preterm individuals demonstrated elevated psychopathology compared with full-term
      controls. Their psychiatric risk was characterized by a non-specific clinical
      profile and was associated with lower IQ.

PMID- 29350126
TI  - A review of the neurobiology of obesity and the available pharmacotherapies.
AB  - Obesity is becoming an increasing problem worldwide. In addition to causing many
      physical health consequences, there is increasing evidence demonstrating that
      obesity is toxic to the brain and, as such, can be considered a disease of the
      central nervous system. Peripheral level regulators of appetite, such as leptin,
      insulin, ghrelin, and cholecystokinin, feed into the appetite center of the
      brain, which is controlled by the hypothalamus, to maintain homeostasis and
      energy balance. However, food consumption is not solely mediated by energy
      balance, but is also regulated by the mesolimbic reward system, where motivation,
      reward, and reinforcement factors influence obesity. The purpose of this review
      is to highlight the neurobiology of eating behavior and obesity and to describe
      various neurobiological treatment mechanisms to treat obesity.

PMID- 29350127
TI  - Converting oral to long-acting injectable antipsychotics: a guide for the
      perplexed.
AB  - There has been increasing recognition that antipsychotic nonadherence is common
      across all stages of schizophrenia, starting from the first episode. Moreover,
      numerous meta-analyses of the existing literature indicate superiority of long
      acting injectable (LAI) over oral antipsychotics when one adjusts for the greater
      illness severity and duration among patients in LAI antipsychotic trials. The
      increasing availability of LAI antipsychotic options has raised interest in
      converting patients from oral medication; however, the successful transition from
      oral to the comparable LAI antipsychotic requires an understanding of the current
      extent of antipsychotic exposure, the kinetics of the LAI preparation, and the
      expected plasma levels achieved by the LAI formulation. The purpose of this
      article is to provide, in a concise format, the essential information for
      converting patients to the LAI forms of haloperidol, fluphenazine, risperidone,
      paliperidone, olanzapine, and aripiprazole from the comparable oral medication,
      and how the use of plasma antipsychotic levels can be invaluable for this
      process.

PMID- 29350128
TI  - Between a rock-a-bye and a hard place: mood disorders during the peripartum
      period.
AB  - Mood disorders including major depressive disorder and bipolar disorder are
      common during and after pregnancy. Timely identification and appropriate
      management of mood episodes is essential to maximize maternal well-being and
      minimize adverse outcomes. Failure to do so results in maternal suffering and
      impaired child bonding, and has the potential for devastating outcomes including
      suicide and infanticide. Women are routinely screened for unipolar depression
      during or after pregnancy but not for bipolar disorder, in spite of the fact that
      childbirth is associated with a major risk for onset or exacerbation of bipolar
      disorder. Delays in detection as well as misdiagnosis of bipolar disorder as
      major depressive disorder may put women at risk of many adverse consequences,
      including symptom exacerbation, psychiatric hospitalization, and suicide. A
      thorough psychiatric assessment is necessary to establish diagnosis, to address
      safety issues, and to formulate a treatment plan. Treatment of mood disorders
      during pregnancy is complicated by the potential risks of fetal exposure to
      psychotropic medications, and the use of these medications during the postpartum
      period may result in infant medication exposure through breastmilk. These risks
      of psychotropic medication exposure must be weighed against the risk of untreated
      mood disorders. This review will discuss the pathophysiology, epidemiology,
      diagnosis, and treatment of mood disorders during pregnancy and the postpartum
      period. Screening tools that can be used in the primary care and obstetrics
      settings to assist in identifying women with peripartum mood disorders will also
      be discussed.

PMID- 29350129
TI  - New medications for treatment-resistant depression: a brief review of recent
      developments.
AB  - There is a great unmet need for new medications with novel mechanisms of action
      that can effectively treat patients who do not benefit from standard
      antidepressant therapies. After a period in which it seemed as if the
      pharmaceutical pipeline for new antidepressants was going dry, the past decade
      has witnessed renewed interest, beginning with discovery of the antidepressant
      effects of ketamine. This article briefly highlights more recent research on
      ketamine and other investigational antidepressants.

PMID- 29350130
TI  - Ecology and Evolution of Chromosomal Gene Transfer between Environmental
      Microorganisms and Pathogens.
AB  - Inspection of the genomes of bacterial pathogens indicates that their pathogenic
      potential relies, at least in part, on the activity of different elements that
      have been acquired by horizontal gene transfer from other (usually unknown)
      microorganisms. Similarly, in the case of resistance to antibiotics, besides
      mutation-driven resistance, the incorporation of novel resistance genes is a
      widespread evolutionary procedure for the acquisition of this phenotype. Current
      information in the field supports the idea that most (if not all) genes acquired
      by horizontal gene transfer by bacterial pathogens and contributing to their
      virulence potential or to antibiotic resistance originate in environmental, not
      human-pathogenic, microorganisms. Herein I discuss the potential functions that
      the genes that are dubbed virulence or antibiotic resistance genes may have in
      their original hosts in nonclinical, natural ecosystems. In addition, I discuss
      the potential bottlenecks modulating the transfer of virulence and antibiotic
      resistance determinants and the consequences in terms of speciation of acquiring
      one or another of both categories of genes. Finally, I propose that exaptation, a
      process by which a change of function is achieved by a change of habitat and not
      by changes in the element with the new functionality, is the basis of the
      evolution of virulence determinants and of antibiotic resistance genes.

PMID- 29350131
TI  - Antimicrobial Resistance in Stenotrophomonas spp.
AB  - Bacteria of the genus Stenotrophomonas are found throughout the environment, in
      close association with soil, sewage, and plants. Stenotrophomonas maltophilia,
      the first member of this genus, is the predominant species, observed in soil,
      water, plants, animals, and humans. It is also an opportunistic pathogen
      associated with the increased number of infections in both humans and animals in
      recent years. In this article, we summarize all Stenotrophomonas species (mainly
      S. maltophilia) isolated from animals and food products of animal origin and
      further distinguish all isolates based on antimicrobial susceptibility and
      resistance phenotypes. The various mechanisms of both intrinsic and acquired
      antimicrobial resistance, which were mainly identified in S. maltophilia isolates
      of nosocomial infections, have been classified as follows: multidrug efflux
      pumps; resistance to beta-lactams, aminoglycosides, quinolones, trimethoprim
      sulfamethoxazole, and phenicols; and alteration of lipopolysaccharide and two
      component regulatory systems. The dissemination, coselection, and persistence of
      resistance determinants among S. maltophilia isolates have also been elaborated.

PMID- 29350132
TI  - Toward Forensic Uses of Microbial Source Tracking.
AB  - The science of microbial source tracking has allowed researchers and watershed
      managers to go beyond general indicators of fecal pollution in water such as
      coliforms and enterococci, and to move toward an understanding of specific
      contributors to water quality issues. The premise of microbial source tracking is
      that characteristics of microorganisms that are strongly associated with
      particular host species can be used to trace fecal pollution to particular animal
      species (including humans) or groups, e.g., ruminants or birds. Microbial source
      tracking methods are practiced largely in the realm of research, and none are
      approved for regulatory uses on a federal level. Their application in the
      conventional sense of forensics, i.e., to investigate a crime, has been limited,
      but as some of these methods become standardized and recognized in a regulatory
      context, they will doubtless play a larger role in applications such as total
      maximum daily load assessment, investigations of sewage spills, and contamination
      from agricultural practices.

PMID- 29350133
TI  - Borrelia miyamotoi Infections in Humans and Ticks, Northeastern China.
AB  - We conducted an investigation of Borrelia miyamotoi infections in humans and
      ticks in northeastern China. Of 984 patients reporting recent tick bites, 14
      (1.4%) were found to be infected with B. miyamotoi by PCR and genomic sequencing.
      The 14 patients had nonspecific febrile manifestations, including fever,
      headache, anorexia, asthenia, and arthralgia. Rash, eschar, and regional
      lymphadenopathy were each observed in 1 patient. Four (28.6%) patients were
      hospitalized because of severe disease. B. miyamotoi was detected in 3.0%
      (19/627) of Ixodes persulcatus, 1 (2.8%) of 36 Haemaphysalis concinna, and none
      of 29 Dermacentor silvarum ticks. Phylogenetic analyses based on sequences of a
      nearly entire 16s rRNA gene, a partial flagellin gene, and the
      glycerophosphodiester phosphodiesterase gene revealed that B. miyamotoi
      identified in patients and ticks were clustered in the group of the Siberian
      type. These findings indicate that B. miyamotoi is endemic in northeastern China
      and its public health significance deserves further investigation.

PMID- 29350134
TI  - Hypervirulent Klebsiella pneumoniae in Cryptogenic Liver Abscesses, Paris,
      France.
AB  - Liver abscesses containing hypervirulent Klebsiella pneumoniae have emerged
      during the past 2 decades, originally in Southeast Asia and then worldwide. We
      hypothesized that hypervirulent K. pneumoniae might also be emerging in France.
      In a retrospective, monocentric, cohort study, we analyzed characteristics and
      outcomes for 199 consecutive patients in Paris, France, with liver abscesses
      during 2010-2015. We focused on 31 patients with abscesses containing K.
      pneumoniae. This bacterium was present in most (14/27, 52%) cryptogenic liver
      abscesses. Cryptogenic K. pneumoniae abscesses were more frequently community
      acquired (p<0.00001) and monomicrobial (p = 0.008), less likely to involve cancer
      patients (p<0.01), and relapsed less often (p<0.01) than did noncryptogenic K.
      pneumoniae liver abscesses. K. pneumoniae isolates from cryptogenic abscesses
      belonged to either the K1 or K2 serotypes and had more virulence factors than
      noncryptogenic K. pneumoniae isolates. Hypervirulent K. pneumoniae are emerging
      as the main pathogen isolated from cryptogenic liver abscesses in the study area.

PMID- 29350135
TI  - Plasmid-Encoded Transferable mecB-Mediated Methicillin Resistance in
      Staphylococcus aureus.
AB  - During cefoxitin-based nasal screening, phenotypically categorized methicillin
      resistant Staphylococcus aureus (MRSA) was isolated and tested negative for the
      presence of the mecA and mecC genes as well as for the SCCmec-orfX junction
      region. The isolate was found to carry a mecB gene previously described for
      Macrococcus caseolyticus but not for staphylococcal species. The gene is flanked
      by beta-lactam regulatory genes similar to mecR, mecI, and blaZ and is part of an
      84.6-kb multidrug-resistance plasmid that harbors genes encoding additional
      resistances to aminoglycosides (aacA-aphD, aphA, and aadK) as well as macrolides
      (ermB) and tetracyclines (tetS). This further plasmidborne beta-lactam resistance
      mechanism harbors the putative risk of acceleration or reacceleration of MRSA
      spread, resulting in broad ineffectiveness of beta-lactams as a main therapeutic
      application against staphylococcal infections.

PMID- 29350136
TI  - Ecologic Features of Plague Outbreak Areas, Democratic Republic of the Congo,
      2004-2014.
AB  - During 2004-2014, the Democratic Republic of the Congo (DRC) declared 54% of
      plague cases worldwide. Using national data, we characterized the epidemiology of
      human plague in DRC for this period. All 4,630 suspected human plague cases and
      349 deaths recorded in DRC came from Orientale Province. Pneumonic plague cases
      (8.8% of total) occurred during 2 major outbreaks in mining camps in the
      equatorial forest, and some limited outbreaks occurred in the Ituri highlands.
      Epidemics originated in 5 health zones clustered in Ituri, where sporadic bubonic
      cases were recorded throughout every year. Classification and regression tree
      characterized this cluster by the dominance of ecosystem 40 (mountain tropical
      climate). In conclusion, a small, stable, endemic focus of plague in the
      highlands of the Ituri tropical region persisted, acting as a source of outbreaks
      in DRC.

PMID- 29350137
TI  - Multiplex PCR-Based Next-Generation Sequencing and Global Diversity of Seoul
      Virus in Humans and Rats.
AB  - Seoul virus (SEOV) poses a worldwide public health threat. This virus, which is
      harbored by Rattus norvegicus and R. rattus rats, is the causative agent of
      hemorrhagic fever with renal syndrome (HFRS) in humans, which has been reported
      in Asia, Europe, the Americas, and Africa. Defining SEOV genome sequences plays a
      critical role in development of preventive and therapeutic strategies against the
      unique worldwide hantavirus. We applied multiplex PCR-based next-generation
      sequencing to obtain SEOV genome sequences from clinical and reservoir host
      specimens. Epidemiologic surveillance of R. norvegicus rats in South Korea during
      2000-2016 demonstrated that the serologic prevalence of enzootic SEOV infections
      was not significant on the basis of sex, weight (age), and season. Viral loads of
      SEOV in rats showed wide dissemination in tissues and dynamic circulation among
      populations. Phylogenetic analyses showed the global diversity of SEOV and
      possible genomic configuration of genetic exchanges.

PMID- 29350138
TI  - Increase in Ocular Syphilis Cases at Ophthalmologic Reference Center, France,
      2012-2015.
AB  - We describe the frequency, demographic and clinical features, and visual outcomes
      of ocular syphilis infections observed during 2012-2015 at a tertiary reference
      center in Paris, France. Twenty-one cases (29 eyes) were identified. The
      occurrence of ocular syphilis increased from 1 case in 2012 to 5 cases in 2013, 6
      cases in 2014, and 9 cases in 2015 (2.22-25.21/1,000 individual patients/year for
      the period). Among case-patients, an annual 20%-33% were co-infected with HIV.
      Seventy-six percent of ocular syphilis infections occurred in men who have sex
      with men. Seventy-five percent of case-patients had a good final visual outcome
      (best-corrected visual acuity >0.3 logMAR score). Visual outcome was worse for
      HIV-positive patients than for HIV-negative patients (p = 0.0139). At follow-up,
      the best visual outcomes were observed in patients whose mean time from first
      ocular symptom to consultation was 15 days (SD +19 days).

PMID- 29350139
TI  - Echinococcus spp. Tapeworms in North America.
AB  - Alveolar and cystic echinococcosis are emerging and reemerging in Europe, Africa,
      and Asia. The expansion of Echinococcus spp. tapeworms in wildlife host
      reservoirs appears to be driving this emergence in some areas. Recent studies
      suggest a similar phenomenon may be occurring in North America. We describe the
      context of Echinococcus spp. research in North America, with a specific focus on
      the contiguous United States. Although studies were conducted in the United
      States throughout the 1900s on various sylvatic and domestic Echinococcus spp.
      tapeworm cycles, data are lacking for the past ~30 years. We review previous
      research, provide analysis of more recent focal studies, and suggest that
      Echinococcus spp. tapeworms, in particular E. canadensis, may be underrecognized.
      As a result, we suggest that additional research and surveillance be conducted
      for these tapeworms in wildlife host reservoirs across the United States.

PMID- 29350140
TI  - Co-circulation of Influenza A H5, H7, and H9 Viruses and Co-infected Poultry in
      Live Bird Markets, Cambodia.
AB  - Longitudinal surveillance of 2 live bird markets in Cambodia revealed year-round,
      high co-circulation of H5, H7, and H9 influenza viruses. We detected influenza A
      viruses in 51.3% of ducks and 39.6% of chickens, and co-infections, mainly by H5
      and H9 viruses, in 0.8% of ducks and 4.5% of chickens.

PMID- 29350141
TI  - Spread of Meropenem-Resistant Streptococcus pneumoniae Serotype 15A-ST63 Clone in
      Japan, 2012-2014.
AB  - After the introduction of pneumococcal conjugate vaccines, the incidence of
      pneumococcal infections due to meropenem-resistant serotype 15A-ST63 strains
      increased in Japan. By using whole-genome sequencing and comparing sequences with
      those of clones from the United Kingdom, the United States, and Canada, we
      clarified the traits of the serotype 15A-ST63 clone. Our analysis revealed that
      the meropenem-resistant serotype 15A-ST63 strains from Japan originated from
      meropenem-susceptible strains from Japan. Recombination site prediction analysis
      showed that the meropenem-resistant strain-specific recombination regions
      included the pbp1a and pbp2b regions. A detailed analysis of the composition of
      these genes indicated that resistance seems to be caused by pbp1a recombination.
      The pbp1a gene in meropenem-resistant isolates was identical to that in multidrug
      (including meropenem)-resistant serotype 19A-ST320 pneumococci, which have spread
      in the United States. The global spread of pneumococci of this lineage is
      noteworthy because serotype 15A is not included in the currently used 13-valent
      pneumococcal conjugate vaccine.

PMID- 29350142
TI  - Lethal Respiratory Disease Associated with Human Rhinovirus C in Wild
      Chimpanzees, Uganda, 2013.
AB  - We describe a lethal respiratory outbreak among wild chimpanzees in Uganda in
      2013 for which molecular and epidemiologic analyses implicate human rhinovirus C
      as the cause. Postmortem samples from an infant chimpanzee yielded near-complete
      genome sequences throughout the respiratory tract; other pathogens were absent.
      Epidemiologic modeling estimated the basic reproductive number (R0) for the
      epidemic as 1.83, consistent with the common cold in humans. Genotyping of 41
      chimpanzees and examination of 24 published chimpanzee genomes from subspecies
      across Africa showed universal homozygosity for the cadherin-related family
      member 3 CDHR3-Y529 allele, which increases risk for rhinovirus C infection and
      asthma in human children. These results indicate that chimpanzees exhibit a
      species-wide genetic susceptibility to rhinovirus C and that this virus,
      heretofore considered a uniquely human pathogen, can cross primate species
      barriers and threatens wild apes. We advocate engineering interventions and
      prevention strategies for rhinovirus infections for both humans and wild apes.

PMID- 29350143
TI  - Adenovirus Type 4 Respiratory Infections among Civilian Adults, Northeastern
      United States, 2011-20151.
AB  - Human adenovirus type 4 (HAdV-4) is most commonly isolated in military settings.
      We conducted detailed molecular characterization on 36 HAdV-4 isolates recovered
      from civilian adults with acute respiratory disease (ARD) in the northeastern
      United States during 2011-2015. Specimens came from college students, residents
      of long-term care facilities or nursing homes, a cancer patient, and young adults
      without co-morbidities. HAdV-4 genome types 4a1 and 4a2, the variants most
      frequently detected among US military recruits in basic training before the
      restoration of vaccination protocols, were isolated in most cases. Two novel a
      like variants were recovered from students enrolled at a college in Tompkins
      County, New York, USA, and a prototype-like variant distinguishable from the
      vaccine strain was isolated from an 18-year-old woman visiting a physician's
      office in Ulster County, New York, USA, with symptoms of influenza-like illness.
      Our data suggest that HAdV-4 might be an underestimated causative agent of ARD
      among civilian adults.

PMID- 29350144
TI  - Emergomyces africanus in Soil, South Africa.
AB  - We detected Emergomyces africanus, a thermally dimorphic fungus that causes an
      HIV-associated systemic mycosis, by PCR in 18 (30%) of 60 soil samples from a
      wide range of habitats in South Africa. Direct and indirect culture techniques
      were unsuccessful. Experimental intraperitoneal inoculation of conidia induced
      murine disease.

PMID- 29350145
TI  - Development of a Pediatric Ebola Predictive Score, Sierra Leone1.
AB  - We compared children who were positive for Ebola virus disease (EVD) with those
      who were negative to derive a pediatric EVD predictor (PEP) score. We collected
      data on all children <13 years of age admitted to 11 Ebola holding units in
      Sierra Leone during August 2014-March 2015 and performed multivariable logistic
      regression. Among 1,054 children, 309 (29%) were EVD positive and 697 (66%) EVD
      negative, with 48 (5%) missing. Contact history, conjunctivitis, and age were the
      strongest positive predictors for EVD. The PEP score had an area under receiver
      operating characteristics curve of 0.80. A PEP score of 7/10 was 92% specific and
      44% sensitive; 3/10 was 30% specific, 94% sensitive. The PEP score could
      correctly classify 79%-90% of children and could be used to facilitate triage
      into risk categories, depending on the sensitivity or specificity required.

PMID- 29350146
TI  - Macacine Herpesvirus 1 Antibody Prevalence and DNA Shedding among Invasive Rhesus
      Macaques, Silver Springs State Park, Florida, USA.
AB  - We compiled records on macacine herpesvirus 1 (McHV-1) seroprevalence and, during
      2015-2016, collected saliva and fecal samples from the free-ranging rhesus
      macaques of Silver Springs State Park, a popular public park in central Florida,
      USA, to determine viral DNA shedding and perform sequencing. Phylogenetic
      analysis of the US5 and US5-US6 intragenic sequence from free-ranging and
      laboratory McHV-1 variants did not reveal genomic differences. In animals
      captured during 2000-2012, average annual seroprevalence was 25% +/- 9 (mean +/-
      SD). We found 4%-14% (95% CI 2%-29%) of macaques passively sampled during the
      fall 2015 mating season shed McHV-1 DNA orally. We did not observe viral shedding
      during the spring or summer or from fecal samples. We conclude that these
      macaques can shed McHV-1, putting humans at risk for exposure to this potentially
      fatal pathogen. Management plans should be put in place to limit transmission of
      McHV-1 from these macaques.

PMID- 29350147
TI  - Fly Reservoir Associated with Wohlfahrtiimonas Bacteremia in a Human.
AB  - Wohlfahrtiimonas species bacteria were isolated from the bloodstream of a patient
      with septicemia and wound myiasis. Environmental investigations identified a
      Wohlfahrtiimonas sp. among insects in the Americas and in a previously
      undescribed vector, the green bottle fly (Lucilia sericata). The isolates
      possibly represent a new species within the genus Wohlfahrtiimonas.

PMID- 29350148
TI  - Scrub Typhus Outbreak in Chonburi Province, Central Thailand, 2013.
AB  - Investigation of a scrub typhus outbreak in Thailand during September 2013 found
      that 9.1% of Thai soldiers and 11.1% of residents living in areas surrounding
      training sites had antibodies against the causative agent, Orientia
      tsutsugamushi. Sequence analysis of O. tsutsugamushi from rodents and chiggers
      identified 7 genogroups and 3 genotypes.

PMID- 29350149
TI  - Cysticercosis in Shandong Province, Eastern China.
AB  - We analyzed demographic and clinical data and estimated the incidence of
      cysticercosis in Shandong Province, China, during 1975-2014. Our analyses showed
      that a cysticercosis-endemic area is present in Shandong Province, especially in
      its western regions. Improved surveillance and control are needed to address the
      elevated risk for cysticercosis in this region.

PMID- 29350150
TI  - Role of Environmental Factors in Shaping Spatial Distribution of Salmonella
      enterica Serovar Typhi, Fiji.
AB  - Fiji recently experienced a sharp increase in reported typhoid fever cases. To
      investigate geographic distribution and environmental risk factors associated
      with Salmonella enterica serovar Typhi infection, we conducted a cross-sectional
      cluster survey with associated serologic testing for Vi capsular antigen-specific
      antibodies (a marker for exposure to Salmonella Typhi in Fiji in 2013. Hotspots
      with high seroprevalence of Vi-specific antibodies were identified in
      northeastern mainland Fiji. Risk for Vi seropositivity increased with increased
      annual rainfall (odds ratio [OR] 1.26/quintile increase, 95% CI 1.12-1.42), and
      decreased with increased distance from major rivers and creeks (OR 0.89/km
      increase, 95% CI 0.80-0.99) and distance to modeled flood-risk areas (OR
      0.80/quintile increase, 95% CI 0.69-0.92) after being adjusted for age, typhoid
      fever vaccination, and home toilet type. Risk for exposure to Salmonella Typhi
      and its spatial distribution in Fiji are driven by environmental factors. Our
      findings can directly affect typhoid fever control efforts in Fiji.

PMID- 29350151
TI  - Risk Communication and Ebola-Specific Knowledge and Behavior during 2014-2015
      Outbreak, Sierra Leone.
AB  - We assessed the effect of information sources on Ebola-specific knowledge and
      behavior during the 2014-2015 Ebola virus disease outbreak in Sierra Leone. We
      pooled data from 4 population-based knowledge, attitude, and practice surveys
      (August, October, and December 2014 and July 2015), with a total of 10,604
      respondents. We created composite variables for exposures (information sources:
      electronic, print, new media, government, community) and outcomes (knowledge and
      misconceptions, protective and risk behavior) and tested associations by using
      logistic regression within multilevel modeling. Exposure to information sources
      was associated with higher knowledge and protective behaviors. However, apart
      from print media, exposure to information sources was also linked to
      misconceptions and risk behavior, but with weaker associations observed.
      Knowledge and protective behavior were associated with the outbreak level, most
      strongly after the peak, whereas risk behavior was seen at all levels of the
      outbreak. In future outbreaks, close attention should be paid to dissemination of
      information.

PMID- 29350152
TI  - Epidemic Varicella Zoster Virus among University Students, India.
AB  - We investigated a yearlong varicella zoster virus outbreak in a highly
      susceptible young adult population at a large university in India. Outbreaks of
      varicella infection among adults are not well described in the literature.
      Infection control measures and vaccination policy for this age group and setting
      are needed.

PMID- 29350153
TI  - Trends in Infectious Disease Mortality, South Korea, 1983-2015.
AB  - We used national statistics from 1983-2015 to evaluate trends in mortality caused
      by infectious diseases in South Korea. Age-standardized mortality from infectious
      disease decreased from 43.5/100,000 population in 1983 to 16.5/100,000 in 1996,
      and then increased to 44.6/100,000 in 2015. Tuberculosis was the most common
      cause of death in 1983 and respiratory tract infections in 2015. We observed a
      significant decline in infant deaths caused by infectious diseases, but mortality
      in persons age >65 years increased from 135 deaths/100,000 population in 1996 to
      307/100,000 in 2015. The relative inequality indices for respiratory tract
      infections, sepsis, and tuberculosis tended to increase over time. Although
      substantial progress has been achieved in terms of infant mortality, death rates
      from infectious disease has not decreased overall. Elderly populations with lower
      education levels and subgroups susceptible to respiratory infections and sepsis
      should be the focus of preventive policies.

PMID- 29350154
TI  - Use of Pristinamycin for Macrolide-Resistant Mycoplasma genitalium Infection.
AB  - High levels of macrolide resistance and increasing fluoroquinolone resistance are
      found in Mycoplasma genitalium in many countries. We evaluated pristinamycin for
      macrolide-resistant M. genitalium in a sexual health center in Australia.
      Microbiologic cure was determined by M. genitalium-specific 16S PCR 14-90 days
      after treatment began. Of 114 persons treated with pristinamycin, infection was
      cured in 85 (75%). This percentage did not change when pristinamycin was given at
      daily doses of 2 g or 4 g or at 3 g combined with 200 mg doxycycline. In
      infections with higher pretreatment bacterial load, treatment was twice as likely
      to fail for each 1 log10 increase in bacterial load. Gastrointestinal side
      effects occurred in 7% of patients. Pristinamycin at maximum oral dose, or
      combined with doxycycline, cured 75% of macrolide-resistant M. genitalium
      infections. Pristinamycin is well-tolerated and remains an option where
      fluoroquinolones have failed or cannot be used.

PMID- 29350155
TI  - Yersinia pestis Survival and Replication in Potential Ameba Reservoir.
AB  - Plague ecology is characterized by sporadic epizootics, then periods of dormancy.
      Building evidence suggests environmentally ubiquitous amebae act as feral
      macrophages and hosts to many intracellular pathogens. We conducted environmental
      genetic surveys and laboratory co-culture infection experiments to assess whether
      plague bacteria were resistant to digestion by 5 environmental ameba species.
      First, we demonstrated that Yersinia pestis is resistant or transiently resistant
      to various ameba species. Second, we showed that Y. pestis survives and
      replicates intracellularly within Dictyostelium discoideum amebae for ?48 hours
      postinfection, whereas control bacteria were destroyed in <1 hour. Finally, we
      found that Y. pestis resides within ameba structures synonymous with those found
      in infected human macrophages, for which Y. pestis is a competent pathogen.
      Evidence supporting amebae as potential plague reservoirs stresses the importance
      of recognizing pathogen-harboring amebae as threats to public health,
      agriculture, conservation, and biodefense.

PMID- 29350156
TI  - Dengue-Associated Posterior Reversible Encephalopathy Syndrome, Vietnam.
AB  - Dengue can cause neurologic complications in addition to the more common
      manifestations of plasma leakage and coagulopathy. Posterior reversible
      encephalopathy syndrome has rarely been described in dengue, although the
      pathophysiology of endothelial dysfunction likely underlies both. We describe a
      case of dengue-associated posterior reversible encephalopathy syndrome and
      discuss diagnosis and management.

PMID- 29350157
TI  - Relative Risk for Ehrlichiosis and Lyme Disease Where Vectors for Both Are
      Sympatric, Southeastern United States.

PMID- 29350158
TI  - Human African Trypanosomiasis in Emigrant Returning to China from Gabon, 2017.
AB  - Human African trypanosomiasis is endemic to parts of sub-Saharan Africa and
      should be considered in the differential diagnosis of patients who have visited
      or lived in Africa. We report a 2017 case of stage 2 Trypanosoma brucei gambiense
      disease in an emigrant who returned to China from Gabon.

PMID- 29350159
TI  - Clinical and Molecular Epidemiology of Staphylococcal Toxic Shock Syndrome in the
      United Kingdom.
AB  - Staphylococcal toxic shock syndrome (TSS) was originally described in
      menstruating women and linked to TSS toxin 1 (TSST-1)-producing Staphylococcus
      aureus. Using UK national surveillance data, we ascertained clinical, molecular
      and superantigenic characteristics of TSS cases. Average annual TSS incidence was
      0.07/100,000 population. Patients with nonmenstrual TSS were younger than those
      with menstrual TSS but had the same mortality rate. Children <16 years of age
      accounted for 39% of TSS cases, most caused by burns and skin and soft tissue
      infections. Nonmenstrual TSS is now more common than menstrual TSS in the UK,
      although both types are strongly associated with the tst+ clonal complex (CC) 30
      methicillin-sensitive S. aureus lineage, which accounted for 49.4% of all TSS and
      produced more TSST-1 and superantigen bioactivity than did tst+ CC30 methicillin
      resistant S. aureus strains. Better understanding of this MSSA lineage and
      infections in children could focus interventions to prevent TSS in the future.

PMID- 29350160
TI  - Effects of Culling on Leptospira interrogans Carriage by Rats.
AB  - We found that lethal, urban rat control is associated with a significant increase
      in the odds that surviving rats carry Leptospira interrogans. Our results suggest
      that human interventions have the potential to affect and even increase the
      prevalence of zoonotic pathogens within rat populations.

PMID- 29350161
TI  - Invasive Serotype 35B Pneumococci Including an Expanding Serotype Switch Lineage.

PMID- 29350162
TI  - New Parvovirus Associated with Serum Hepatitis in Horses after Inoculation of
      Common Biological Product.
AB  - Equine serum hepatitis (i.e., Theiler's disease) is a serious and often life
      threatening disease of unknown etiology that affects horses. A horse in Nebraska,
      USA, with serum hepatitis died 65 days after treatment with equine-origin tetanus
      antitoxin. We identified an unknown parvovirus in serum and liver of the dead
      horse and in the administered antitoxin. The equine parvovirus-hepatitis (EqPV-H)
      shares <50% protein identity with its phylogenetic relatives of the genus
      Copiparvovirus. Next, we experimentally infected 2 horses using a tetanus
      antitoxin contaminated with EqPV-H. Viremia developed, the horses seroconverted,
      and acute hepatitis developed that was confirmed by clinical, biochemical, and
      histopathologic testing. We also determined that EqPV-H is an endemic infection
      because, in a cohort of 100 clinically normal adult horses, 13 were viremic and
      15 were seropositive. We identified a new virus associated with equine serum
      hepatitis and confirmed its pathogenicity and transmissibility through
      contaminated biological products.

PMID- 29350163
TI  - Amebaborne "Attilina massiliensis" Keratitis, France.
AB  - We report a case of Acanthamoeba castellani keratitis in a person who wore
      contact lenses. The amebae hosted an ameba-resistant bacterial symbiont,
      provisionally named "Attilina massiliensis," a yet undescribed alpha
      Proteobacterium.

PMID- 29350164
TI  - Cerebral Syphilitic Gumma in Immunocompetent Man, Japan.
AB  - Although cerebral syphilitic gummas are generally considered to be rare
      manifestations of tertiary syphilis, many reports exist of early cerebral
      syphilitic gumma. Our finding of cerebral syphilitic gumma in an HIV-negative man
      within 5 months after syphilis infection suggests that this condition should be
      considered in syphilis patients who have neurologic symptoms.

PMID- 29350165
TI  - Novel Streptococcus suis Sequence Type 834 among Humans, Madagascar.
AB  - Two cases of meningitis caused by Streptococcus suis occurred in Madagascar, 1 in
      2015 and 1 in 2016. We report the characterization of the novel sequence type,
      834, which carried the mrp+/sly+/epf+ virulence marker and a mutation G->T at
      position 174, leading to a substitution mutS1 to mutS284.

PMID- 29350166
TI  - Cronobacter sakazakii Infection from Expressed Breast Milk, Australia.
AB  - Cronobacter sakazakii neonatal infections are often epidemiologically linked to
      the consumption of contaminated powdered infant formula. We describe a case
      resulting from consumption of contaminated expressed breast milk, as confirmed by
      whole-genome sequencing. This case highlights potential risks associated with
      storage and acquisition of expressed breast milk.

PMID- 29350167
TI  - Rickettsia africae and Novel Rickettsial Strain in Amblyomma spp. Ticks,
      Nicaragua, 2013.
AB  - We report molecular detection of Rickettsia africae in Amblyomma ovale ticks from
      Nicaragua and a novel rickettsial strain in an A. triste tick. Of 146 ticks from
      dogs, 16.4% were Rickettsia PCR positive. The presence of Rickettsia spp. in
      human-biting ticks in Nicaragua may pose a public health concern.

PMID- 29350168
TI  - Influenza D Virus in Cattle, Ireland.
AB  - We detected influenza D virus in 18 nasal swab samples from cattle in Ireland
      that were clinically diagnosed with respiratory disease. Specimens were obtained
      from archived samples received for routine diagnosis during 2014-2016. Sequencing
      showed that viruses from Ireland clustered with virus sequences obtained in
      Europe within the D/swine/OK/1334/2011 clade.

PMID- 29350169
TI  - Containment of Highly Pathogenic Avian Influenza A(H5N1) Virus, Lebanon, 20161.
AB  - A preparedness plan for avian influenza A(H5N1) virus infection was activated in
      Lebanon in 2016 after reported cases in poultry. Exposed persons were given
      prophylaxis and monitored daily. A total of 185 exposed persons were identified:
      180 received prophylaxis, 181 were monitored, and 41 suspected cases were
      reported. All collected specimens were negative for virus by PCR.

PMID- 29350170
TI  - Atypical lower motor neuron disease with enlargement of Nissl substance: Report
      of an autopsy case.
AB  - The patient was an 81-year-old woman diagnosed with atypical motor neuron disease
      who died after a long clinical course (7.5 years without mechanical assistance of
      ventilation) characterized by lower motor neuron signs and symptoms. Upper motor
      neuron signs and cognitive impairment were not apparent. Autopsy demonstrated
      severe neuronal loss in the anterior horn of the spinal cord, and some of the
      remaining neurons showed enlargement of Nissl substance and apparent thickening
      of the nuclear envelopes. No Bunina bodies, skein-like inclusions, or structures
      immunoreactive for phosphorylated transactivation response DNA-binding protein 43
      were found. Immunoreactivity for superoxide dismutase-1 was focally seen in the
      enlarged Nissl substance. Ultrastructural examination demonstrated an increase of
      rough-surfaced endoplasmic reticulum (rough ER) and free ribosomes,
      disaggregation of polyribosomes, and dispersion of free ribosomes. Cisterns of
      rough ER were slightly dilated, and some of them were closely attached to the
      nuclear envelopes. Enlargement of Nissl substance may be related to "ER stress",
      and the abnormal findings of rough ER and free ribosomes may represent a
      degenerative process. However, another possibility, that they represent a
      compensatory hyperplastic change, cannot be excluded. The close attachment of
      cisterns of rough ER to the nuclear envelopes may be a mechanism to support or
      compensate for the abnormally-fragile nuclear envelopes.?.

PMID- 29350171
TI  - The DNA copy number landscape of a collision tumor.
AB  - Intracranial collision tumors are composed of two histologically distinct but
      merging components, and are rare. Their genetic profile has rarely been
      described. Comparative genome hybridization of a combined meningioma and
      oligodendroglioma demonstrated deletion of chromosome 22q and of 19q in both
      tumors. Somatic deletion of chromosome 22q and 19q is associated with development
      of an intracranial collision tumor.?.

PMID- 29350172
TI  - Comparison of dialysate and plasma NTproBNP in prediction of clinical outcomes of
      diabetic and nondiabetic peritoneal dialysis patients?.
AB  - BACKGROUND: Plasma level of N-terminal pro-brain natriuretic peptide (P-NTproBNP)
      is a useful marker in prediction of mortality in peritoneal dialysis (PD)
      patients. However, the predictive value of spent dialysate counterpart (D
      NTproBNP) of plasma NTproBNP on mortality and dropout is not known. MATERIALS AND
      METHODS: Simultaneous P-NTproBNP and D-NTproBNP assays were performed after an
      overnight dwell in 44 scheduled ambulatory PD patients. Patients were followed
      for ~ 47 months. Deceased patients or patients who were transferred to
      hemodialysis were regarded as dropouts. RESULTS: 14 patients (31.8%) dropped out
      at ~ 4 years (9 deaths and 5 transfers to hemodialysis). Diabetics, males, and
      patients with higher membrane permeability had higher dropout rates. Patients
      with P- and D-NTproBNP higher than median values had higher mortality and dropout
      rates (Kaplan-Meier test, log-rank Test p < 0.05). Odds ratios of D-NTproBNP for
      death and dropouts were (3.807 (0.907 - 15.971), p = 0.068) and (2.87 (1.009 -
      8.138) p = 0.048), respectively; odds ratios of P-NTproBNP for death and dropouts
      were (4.652 (0.914 - 23.693), p = 0.064) and (2.67 (0.924 - 7.716), p = 0.07),
      respectively; in ROC analysis for death, AUC for P- and D-NTproBNP were 0.762
      (0.578 - 0.946, p = 0.016) and 0.765 (0.590 - 0.940, p = 0.015), respectively.
      Exclusion of diabetic patients from the analyses resulted in significant changes
      in the predictive value P- and D-NTproBNP. Although death and dropout rates were
      still higher in nondiabetic patients with higher NTproBNP levels, the differences
      between groups lost statistical significance. CONCLUSIONS: Both P-NTproBNP and D
      NTproBNP are significant predictors of outcomes of interest. Predictive value of
      NTproBNP might be different in diabetics and non-diabetic CAPD patients.?.

PMID- 29350173
TI  - Membranoproliferative glomerulonephritis and interstitial nephritis in the
      setting of Epstein-Barr virus-related hemophagocytic syndrome?.
AB  - BACKGROUND: Hemophagocytic syndrome (HPS) is a rare, aggressive disorder
      characterized by dysregulation of lymphocyte and macrophage activity, which
      culminates in tissue infiltration with hemophagocytosis and ultimately organ
      failure. Renal involvement frequently ensues and usually results in acute tubular
      necrosis with associated interstitial inflammation. Less frequently,
      glomerulopathy can also be found. CASE: We report a case of a 24-year-old
      Caucasian woman with previous asymptomatic hematuria, mild proteinuria, and
      normal renal function who presented to us with fever. Laboratory findings
      revealed pancytopenia, elevated lactate dehydrogenase, and ferritin as well as
      liver and kidney failure. Renal biopsy showed a tubulointerstitial nephritis
      superimposed in a membranoproliferative glomerulonephritis with crescents.
      Extensive etiologic investigation was negative except for Epstein-Barr virus
      (EBV) viral load. EBV-DNA was then identified by in situ hybridization in the
      renal biopsy. HPS could be diagnosed with the presence of six criteria: fever,
      splenomegaly, bicytopenia, high ferritin, hypertriglyceridemia, and high levels
      of soluble CD25. Steroid therapy was initiated with resolution of HPS as well as
      complete recovery of renal and liver function. CONCLUSION: In this case, we
      believe that EBV triggered both HPS and tubulointerstitial nephritis. Steroid
      therapy successfully treated the inflammatory syndrome, allowing renal function
      recovery without compromising EBV infection resolution.?.

PMID- 29350174
TI  - Automated peritoneal dialysis could rapidly improve left heart failure by
      increasing peritoneal dialysis ultrafiltration: a single-center observational
      clinical study?.
AB  - Ultrafiltration failure (UFF) is a major cause of water retention, left heart
      failure (LHF), and peritoneal dialysis (PD) failure. Automated peritoneal
      dialysis (APD) might have better ultrafiltration (UF) than continuous ambulatory
      peritoneal dialysis (CAPD). Here, we have studied whether short-term APD could
      increase UF and improve LHF. 47 patients were included in this study from
      December 1, 2015, to January 1, 2017. All patients had been treated with CAPD
      before they came to our center and were treated with APD in the hospital. 24-hour
      peritoneal UF volume, 24-hour urine volume, body weight, blood pressure, LHF
      class, serum creatinine, blood urea nitrogen, albumin, potassium, hemoglobin, and
      glucose were collected and compared before and after receiving short-time APD. A
      total of 47 patients (31 men, mean age 46.8 +/- 16.2 years, mean duration 26
      months (2 - 195 months)) were enrolled in this study. Of the 47 patients,
      peritoneal dialysis UF was significantly increased when receiving short-term APD
      compared to CAPD (1,261.9 +/- 329.6 mL vs. 706.2 +/- 222.3 mL, p < 0.001), and
      body weights had significantly decreased 3 days after treatment with APD (57.73
      +/- 10.5 vs. 59.81 +/- 10.8, p < 0.001). LHF class was significantly decreased 3
      days after receiving APD (1.7 +/- 0.8 vs. 2.4 +/- 1.0, p < 0.001). Blood pressure
      was well controlled 3 days after treatment with APD (146.6 +/- 14.4 vs. 162.5 +/-
      23.8 of SBP, p = 0.007, and 85.6 +/- 11.1 vs. 95.6 +/- 14.7 of DBP, p = 0.001).
      In conclusion, short-term APD could significantly increase ultrafiltration,
      rapidly alleviate edema and improve LHF, and might be an effective method to
      treat UFF and LHF in PD patients.?.

PMID- 29350175
TI  - Update on the nephrotoxicity of novel anticancer agents?.
AB  - Anticancer drug-induced kidney disease is a problem commonly encountered by
      nephrologists. The number of medications employed by oncologists causing acute
      and chronic kidney injury as well as electrolyte and acid-base disturbances has
      increased significantly over the past several decades. While conventional
      chemotherapeutic drugs induce a number of kidney lesions, emergence of very
      effective and well-tolerated targeted therapies and novel immunotherapies has
      increased the occurrence of drug-induced acute and chronic kidney injury in
      cancer patients. This article will review the various kidney lesions observed
      with these new classes of anticancer drugs.?.

PMID- 29350176
TI  - Pharmacokinetic characterization of three novel 4-mg nicotine lozenges?.
AB  - OBJECTIVE: Nicotine replacement therapy (NRT) increases the probability of
      smoking cessation. This study was conducted to determine if three prototype 4-mg
      nicotine lozenges produced locally in India were bioequivalent to a globally
      marketed reference product, Nicorette(r) 4-mg nicotine lozenge. MATERIALS AND
      METHODS: Healthy adult smokers (N = 39) were treated with three prototype 4-mg
      nicotine lozenges in comparison with a reference 4-mg lozenge in this single
      center, randomized, open-label, single-dose, 4-way crossover study.
      Pharmacokinetic sampling was obtained to test for bioequivalence using maximal
      plasma concentration (Cmax) and extent of absorption (AUC0-t). Secondarily, AUC;0
      infinity, time to maximal plasma concentration (tmax), half-life (T1/2),
      elimination rate constant (Kel), and safety of the prototype lozenges versus the
      reference lozenge were compared. RESULTS: Each prototype 4-mg nicotine lozenge
      was found to be bioequivalent to the reference 4-mg nicotine lozenge based on the
      ratio of geometric means and 90% confidence intervals for Cmax, AUC0-t, and AUC;0
      infinity. Although tmax; was significantly longer for prototype III, all four
      lozenges achieved maximum plasma nicotine concentrations at a median of 1.5
      hours. The safety profiles of the three prototype 4-mg lozenges did not differ
      from that of the 4-mg reference product. CONCLUSION: Each prototype 4-mg nicotine
      lozenge was bioequivalent to the reference 4-mg nicotine lozenge and was well
      tolerated. Furthermore, as these bioequivalent prototypes differed in in-vitro
      dissolution profiles, these data suggest that performance from the in -vitro
      method deployed is not a firm predictor of pharmacokinetic behavior.?.

PMID- 29350177
TI  - Antidepressant medication in a German cohort of patients with Alzheimer's
      disease?.
AB  - OBJECTIVE: The use of antidepressant drugs in dementia patients is associated
      with the risk of adverse events, and the evidence for relevant effects is scarce.
      We aimed to determine the associations between the prescription of
      antidepressants and patients' sociodemographic (e.g., age, gender, living
      situation) and clinical characteristics (e.g., disease severity, neuropsychiatric
      symptoms). MATERIALS AND METHODS: We included 395 institutionalized and community
      dwelling patients with Alzheimer's disease (AD) across all severity stages of
      dementia in a cross-sectional study design. The patients' clinical
      characteristics comprised of cognitive status, daily activities, depressive
      symptoms, further neuropsychiatric symptoms, and health-related quality of life
      (HrQoL). We conducted multiple logistic regression analyses for the association
      between the use of antidepressant drugs and the covariates. RESULTS:
      Approximately 31% of the participants were treated with antidepressant drugs,
      with a higher chance of being medicated for institutionalized patients (chi2
      test: p = 0.010). In the bivariate analyses, the use of antidepressants was
      significantly associated with higher levels of care, lower cognitive and daily
      life capacity, higher extent of neuropsychiatric symptoms, and a lower proxy
      reported HrQoL. Finally, multiple logistic regression models showed a
      significantly higher use of antidepressants in patients treated by psychiatrists
      and neurologists (OR 2.852, 95% CI: 1.223 - 6.652). CONCLUSION: The use of
      antidepressant drugs in the study population was high, and the suitability of the
      treatment with antidepressants remains unclear. Participants with diminished
      cognitive and functional capacity, higher extent of neuropsychiatric symptoms,
      and those treated by neuropsychiatric specialists were more likely to be treated
      with antidepressants. The pharmaceutical treatment of patients with these
      clinical characteristics should be particularly considered in the daily care for
      dementia patients. Further longitudinal studies should evaluate the
      appropriateness of indications for antidepressants and the causative direction of
      correlations with the patients' clinical characteristics.?.

PMID- 29350178
TI  - Use of rifabutin to treat tuberculosis in a cardiac transplant recipient: A case
      report?.
AB  - OBJECTIVE: Tuberculosis is an important concern following organ transplantation.
      Unfortunately, several antituberculosis drugs interact with immunosuppressants.
      This report describes our experience with rifabutin (RBT) in the treatment of
      acute tuberculosis in a cardiac transplant recipient. CASE: A 61-year-old cardiac
      transplant recipient developed tuberculosis meningitis during treatment of
      miliary tuberculosis. RBT was given for 27 days concomitantly with cyclosporine
      (CsA). CsA concentrations at 0 hour (C<sub>0</sub>) decreased within 3 days of
      starting RBT. The serum concentration-curve from 0 to 12 hours (AUC<sub>0
      12h</sub>)/dose 7 days after starting RBT therapy decreased by 28%, compared to
      the values before RBT therapy. The apparent clearance at both 7 and 21 days after
      starting RBT therapy was 1.4 times higher than before RBT therapy. CONCLUSION:
      RBT has fewer drug-drug interactions than rifampin and should be preferentially
      used for the treatment of tuberculosis in transplant patients treated with CsA.
      Close monitoring of CsA blood concentration during RBT therapy minimized the risk
      of under- or over-immunosuppression in a cardiac transplant patient.?.

PMID- 29350179
TI  - Risks in the clinical applications of scopolamine butylbromide injections.
AB  - OBJECTIVE: To investigate and analyze the clinical application of scopolamine
      butylbromide injection and promote the rational use of the drug. MATERIALS AND
      METHODS: We classified and analyzed 3,695 cases of scopolamine butylbromide
      injection (effective cases only) collected over the period of January 2016 to
      July 2017, including details on gender, age, course of treatment, high-risk
      patients with other medications, adverse drug reactions, and drug combinations.
      RESULTS: Use in high-risk patients is common, occurrence of adverse drug reaction
      rate in patients with high risk is 8.32 times the incidence of adverse reactions
      of the drug in general, in high-risk patients with adverse drug reaction the rate
      is 7.63 times that for lower-risk patients. Combined use of drugs is common, and
      there are 1.98% of cases with potential drug interactions. CONCLUSION: The
      findings have importance for other Asian ethnic groups and for Chinese living
      outside China - Chinese are considered a "moderate-risk" ethnic group in using
      scopolamine butylbromide injection. We should adhere to the requirements of drug
      instructions, pay attention to high-risk patients, drug and drug interactions,
      drug and food interactions, reduce the risk of adverse drug reactions, and ensure
      drug safety.

PMID- 29350180
TI  - Genetic characterization of three mitochondrial gene sequences of goat/sheep
      derived coenurus cerebralis and cysticercus tenuicollis isolates in Inner
      Mongolia, China.
AB  - Taenia multiceps and Taenia hydatigena are widely distributed tapeworms of
      canids. Due to a lack of genetic information on these two parasites in China, in
      this study we analyzed six coenurus cerebralis and two cysticercus tenuicollis
      cysts from goats or sheep in Inner Mongolia, northern China by amplifying three
      mitochondrial genes (cox1, nad4, and cytb). Two haplotypes were obtained at each
      locus for either of the two Taenia cestode species, with ten nucleotide sequences
      being novel. The degrees of genetic variations were 1.18%, 0.61% and 0.52% for
      coenurus cerebralis, and 0.24%, 0.46% and 0.35% for cysticercus tenuicollis at
      the cox1, nad4 and cytb loci, respectively. This is the first molecular
      description of animal-derived metacestodes of T. multiceps and T. hydatigena in
      Inner Mongolia, China. Novel nucleotide sequences might reflect endemic genetic
      characterization of the two cestodes. The present data are useful to explore the
      biological and epidemiological significance of intra-specific variations within
      both Taenia cestodes.

PMID- 29350181
TI  - A single, continuous metric to define tiered serum neutralization potency against
      HIV.
AB  - HIV-1 Envelope (Env) variants are grouped into tiers by their neutralization
      sensitivity phenotype. This helped to recognize that tier 1 neutralization
      responses can be elicited readily, but do not protect against new infections.
      Tier 3 viruses are the least sensitive to neutralization. Because most
      circulating viruses are tier 2, vaccines that elicit neutralization responses
      against them are needed. While tier classification is widely used for viruses, a
      way to rate serum or antibody neutralization responses in comparable terms is
      needed. Logistic regression of neutralization outcomes summarizes serum or
      antibody potency on a continuous, tier-like scale. It also tests significance of
      the neutralization score, to indicate cases where serum response does not depend
      on virus tiers. The method can standardize results from different virus panels,
      and could lead to high-throughput assays, which evaluate a single serum dilution,
      rather than a dilution series, for more efficient use of limited resources to
      screen samples from vaccinees.

PMID- 29350182
TI  - The role of EEG in the diagnosis and classification of the epilepsy syndromes: a
      tool for clinical practice by the ILAE Neurophysiology Task Force (Part 2).
AB  - The concept of epilepsy syndromes, introduced in 1989, was defined as "clusters
      of signs and symptoms customarily occurring together". Definition of epilepsy
      syndromes based on electro-clinical features facilitated clinical practice and,
      whenever possible, clinical research in homogeneous groups of patients with
      epilepsies. Progress in the fields of neuroimaging and genetics made it rapidly
      clear that, although crucial, the electro-clinical description of epilepsy
      syndromes was not sufficient to allow much needed development of targeted
      therapies and a better understanding of the underlying pathophysiological
      mechanisms of seizures. The 2017 ILAE position paper on Classification of the
      Epilepsies recognized that "as a critical tool for the practicing clinician,
      epilepsy classification must be relevant and dynamic to changes in thinking". The
      concept of "epilepsy syndromes" evolved, incorporating issues related to
      aetiologies and comorbidities. A comprehensive update (and revision where
      necessary) of the EEG diagnostic criteria in the light of the 2017 revised
      terminology and concepts was deemed necessary. Part 2 covers the neonatal and
      paediatric syndromes in accordance with the age of onset. [Published with
      educational EEG plates at www.epilepticdisorders.com].

PMID- 29350183
TI  - Integrated biocircuits: engineering functional multicellular circuits and
      devices.
AB  - OBJECTIVE: Implantable neurotechnologies have revolutionized neuromodulatory
      medicine for treating the dysfunction of diseased neural circuitry. However,
      challenges with biocompatibility and lack of full control over neural network
      communication and function limits the potential to create more stable and robust
      neuromodulation devices. Thus, we propose a platform technology of implantable
      and programmable cellular systems, namely Integrated Biocircuits, which use only
      cells as the functional components of the device. APPROACH: We envision the
      foundational principles for this concept begins with novel in vitro platforms
      used for the study and reconstruction of cellular circuitry. Additionally, recent
      advancements in organoid and 3D culture systems account for microenvironment
      factors of cytoarchitecture to construct multicellular circuits as they are
      normally formed in the brain. We explore the current state of the art of these
      platforms to provide knowledge of their advancements in circuit fabrication and
      identify the current biological principles that could be applied in designing
      integrated biocircuit devices. MAIN RESULTS: We have highlighted the exemplary
      methodologies and techniques of in vitro circuit fabrication and propose the
      integration of selected controllable parameters, which would be required in
      creating suitable biodevices. SIGNIFICANCE: We provide our perspective and
      propose new insights into the future of neuromodulaion devices within the scope
      of living cellular systems that can be applied in designing more reliable and
      biocompatible stimulation-based neuroprosthetics.

PMID- 29350184
TI  - Chirality in molecular collision dynamics.
AB  - Chirality is a phenomenon that permeates the natural world, with implications for
      atomic and molecular physics, for fundamental forces and for the mechanisms at
      the origin of the early evolution of life and biomolecular homochirality. The
      manifestations of chirality in chemistry and biochemistry are numerous, the
      striking ones being chiral recognition and asymmetric synthesis with important
      applications in molecular sciences and in industrial and pharmaceutical
      chemistry. Chiral discrimination phenomena, due to the existence of two
      enantiomeric forms, very well known in the case of interaction with light, but
      still nearly disregarded in molecular collision studies. Here we review some
      ideas and recent advances about the role of chirality in molecular collisions,
      designing and illustrating molecular beam experiments for the demonstration of
      chiral effects and suggesting a scenario for a stereo-directional origin of
      chiral selection.

PMID- 29350185
TI  - Fluorescence detection of glutathione and oxidized glutathione in blood with a
      NIR-excitable cyanine probe.
AB  - Cyanine has been widely utilized as a near infrared (NIR) fluorophore for
      detection of glutathione (GSH). However, the excitation of most of the reported
      cyanine-based probes was less than 800 nm, which inevitably induce biological
      background absorption and lower the sensitivity, limiting their use for detection
      of GSH in blood samples. To address this issue, here, a heptamethine cyanine
      probe (DNIR), with a NIR excitation wavelength at 804 nm and a NIR emission
      wavelength at 832 nm, is employed for the detection of GSH and its oxidized form
      (GSSG) in blood. The probe displays excellent selectivity for GSH over GSSG and
      other amino acids, and rapid response to GSH, in particular a good property for
      indirect detection of GSSG in the presence of enzyme glutathione reductase and
      the reducing agent nicotinamideadenine dinucleotide phosphate, without further
      separation prior to fluorescent measurement. To the best of our knowledge, this
      is the first attempt to explore NIR fluorescent approach for the simultaneous
      assay of GSH and GSSG in blood. As such, we expect that our fluorescence sensors
      with both NIR excitation and NIR emission make this strategy suitable for the
      application in complex physiological systems.

PMID- 29350186
TI  - MRI tracing non-invasive TiO2-based nanoparticles activated by ultrasound for
      multi-mechanism therapy of prostatic cancer.
AB  - To reduce the side effects of chemotherapy and achieve effective and safe therapy
      for prostate cancer, herein a simple but multi-functional TiO2:Gd@DOX/FA system
      activated by ultrasound was developed for the MRI-guided multi-mechanism therapy
      of prostate cancer. TiO2 nanoparticles served as a sonosensitizer as well as a
      nanocarrier with the pH-responsive release of DOX. The doping of Gd was not only
      able to endow the TiO2 with magnetic resonance imaging (MRI) ability, but also
      further improve the sonodynamic ability of the TiO2. The characterization of the
      as-prepared TiO2:Gd@DOX/FA showed sensitive pH-responsive drug release, high
      reactive oxygen species (ROS) production, T 1-MRI contrast performance and
      excellent biocompatibility. The cytotoxicity assay in vitro showed cell death up
      to 91.68% after 48 h incubation induced by the TiO2:Gd@DOX + ultrasound group.
      Meanwhile, in the in vivo synergistic therapy studies, the tumor sizes of all the
      nanomedicine groups were smaller than for the free DOX (V:V 0 = 4.2). More
      importantly, the body showed nearly no weight loss. This safety was also
      confirmed by the H&E staining, biodistribution experiment and serum biochemistry
      results. Altogether, TiO2:Gd@DOX/FA significantly reduced the side effects of
      DOX, augmented the levels of ROS and achieved effective and safe therapy,
      indicating its potential for the multi-mechanism therapy of prostate cancer.

PMID- 29350187
TI  - Multifractal dynamics of resting-state functional connectivity in the prefrontal
      cortex.
AB  - : Brain function is organized as a network of functional connections between
      different neuronal populations with connection strengths dynamically changing in
      time and space. Studies investigating functional connectivity (FC) usually follow
      a static approach when describing FC by considering the connectivity strengths
      constant, however a dynamic approach seems more reasonable, as this way the
      spatio-temporal dynamics of the underlying system can also be captured.
      OBJECTIVE: The scale-free, i.e. fractal nature of neural dynamics is an inherent
      property of the nervous system. The aim of this study was to determine if dynamic
      functional connectivity (DFC) in the prefrontal cortex shows not only scale-free
      but indeed multifractal dynamics. APPROACH: Functional near-infrared spectroscopy
      (fNIRS) was used to monitor resting-state brain activity in young healthy
      volunteers. Sliding window correlation (SWC) analysis and graph theory approach
      were utilized to capture the functional connection networks for every time point,
      whose topology was subsequently characterized with three network metrics-Density,
      Clustering Coefficient and Efficiency-each capturing a different aspect of the
      given network. The temporal structuring of the obtained network metric time
      series was then described by multifractal time series analysis. MAIN RESULTS: We
      found the DFC in the prefrontal cortex fluctuating according to scale-free,
      specifically multifractal dynamics. Moreover, different topological properties of
      the network showed different multifractal characteristics. All the results were
      reproducible in all window sizes used in the SWC analysis, however we found that
      the actual values of the given multifractal properties depended significantly on
      the window size. SIGNIFICANCE: Our results may well be another indication of a
      self-organized critical state underlying resting-state brain activity. The
      proposed analysis of functional brain dynamics can also open new perspectives for
      future clinical applications.

PMID- 29350188
TI  - Accurate identification of layer number for few-layer WS2 and WSe2 via
      spectroscopic study.
AB  - Transition metal dichalcogenides (TMDs) with a typical layered structure are
      highly sensitive to their layer number in optical and electronic properties.
      Seeking a simple and effective method for layer number identification is very
      important to low-dimensional TMD samples. Herein, a rapid and accurate layer
      number identification of few-layer WS2 and WSe2 is proposed via locking their
      photoluminescence (PL) peak-positions. As the layer number of WS2/WSe2 increases,
      it is found that indirect transition emission is more thickness-sensitive than
      direct transition emission, and the PL peak-position differences between the
      indirect and direct transitions can be regarded as fingerprints to identify their
      layer number. Theoretical calculation confirms that the notable thickness
      sensitivity of indirect transition derives from the variations of electron
      density of states of W atom d-orbitals and chalcogen atom p-orbitals. Besides,
      the PL peak-position differences between the indirect and direct transitions are
      almost independent of different insulating substrates. This work not only
      proposes a new method for layer number identification via PL studies, but also
      provides a valuable insight into the thickness-dependent optical and electronic
      properties of W-based TMDs.

PMID- 29350189
TI  - Detection of thoracic vascular structures by electrical impedance tomography: a
      systematic assessment of prominence peak analysis of impedance changes.
AB  - OBJECTIVE: Electrical impedance tomography (EIT) is a non-invasive and radiation
      free bedside monitoring technology, primarily used to monitor lung function.
      First experimental data shows that the descending aorta can be detected at
      different thoracic heights and might allow the assessment of central
      hemodynamics, i.e. stroke volume and pulse transit time. APPROACH: First, the
      feasibility of localizing small non-conductive objects within a saline phantom
      model was evaluated. Second, this result was utilized for the detection of the
      aorta by EIT in ten anesthetized pigs with comparison to thoracic computer
      tomography (CT). Two EIT belts were placed at different thoracic positions and a
      bolus of hypertonic saline (10 ml, 20%) was administered into the ascending aorta
      while EIT data were recorded. EIT images were reconstructed using the GREIT
      model, based on the individual's thoracic contours. The resulting EIT images were
      analyzed pixel by pixel to identify the aortic pixel, in which the bolus caused
      the highest transient impedance peak in time. MAIN RESULTS: In the phantom, small
      objects could be located at each position with a maximal deviation of 0.71 cm. In
      vivo, no significant differences between the aorta position measured by EIT and
      the anatomical aorta location were obtained for both measurement planes if the
      search was restricted to the dorsal thoracic region of interest (ROIs).
      SIGNIFICANCE: It is possible to detect the descending aorta at different thoracic
      levels by EIT using an intra-aortic bolus of hypertonic saline. No significant
      differences in the position of the descending aorta on EIT images compared to CT
      images were obtained for both EIT belts.

PMID- 29350190
TI  - Development and validation of a high-resolution mapping platform to aid in the
      public awareness of radiological hazards.
AB  - The distribution, quantification and exposure-related effects of radiation in the
      environment, arising from both natural and anthropogenic sources, is of great
      (and growing) concern for global populations. Recent events at the Fukushima
      Daiichi Nuclear Plant (FDNPP) have further highlighted the importance of
      developing radiation mapping technologies that not only contribute to the
      continued assessment of contamination, but can serve as an educational tool for
      members of the public regarding both its behaviour and extent. With an even
      greater number of people possessing smart-phone technology, a lightweight and
      portable 'connected system' has been developed to demonstrate to users the
      calibrated radioactive dose rate in an area, viewable in real-time through a
      dedicated phone application. As well as allowing for system users to be alerted
      where variations in dose rate are experienced, the combined results from multiple
      systems are viewable through a custom-built desktop application-permitting the
      output obtained via any number of units to be similarly displayed in real-time. A
      successful initial trialling of the system is described at a former tin mine in
      Cornwall (south-west England)-known to exhibit low, but identifiable radiation
      anomalies in discrete areas. Additional applications outside of its educational
      usage are also discussed.

PMID- 29350191
TI  - A prospective gating method to acquire a diverse set of free-breathing CT images
      for model-based 4DCT.
AB  - Breathing motion modeling requires observation of tissues at sufficiently
      distinct respiratory states for proper 4D characterization. This work proposes a
      method to improve sampling of the breathing cycle with limited imaging dose. We
      designed and tested a prospective free-breathing acquisition protocol with a
      simulation using datasets from five patients imaged with a model-based 4DCT
      technique. Each dataset contained 25 free-breathing fast helical CT scans with
      simultaneous breathing surrogate measurements. Tissue displacements were measured
      using deformable image registration. A correspondence model related tissue
      displacement to the surrogate. Model residual was computed by comparing predicted
      displacements to image registration results. To determine a stopping criteria for
      the prospective protocol, i.e. when the breathing cycle had been sufficiently
      sampled, subsets of N scans where 5  ?  N  ?  9 were used to fit reduced models
      for each patient. A previously published metric was employed to describe the
      phase coverage, or 'spread', of the respiratory trajectories of each subset.
      Minimum phase coverage necessary to achieve mean model residual within 0.5 mm of
      the full 25-scan model was determined and used as the stopping criteria. Using
      the patient breathing traces, a prospective acquisition protocol was simulated.
      In all patients, phase coverage greater than the threshold necessary for model
      accuracy within 0.5 mm of the 25 scan model was achieved in six or fewer scans.
      The prospectively selected respiratory trajectories ranked in the (97.5  +/- 
      4.2)th percentile among subsets of the originally sampled scans on average.
      Simulation results suggest that the proposed prospective method provides an
      effective means to sample the breathing cycle with limited free-breathing scans.
      One application of the method is to reduce the imaging dose of a previously
      published model-based 4DCT protocol to 25% of its original value while achieving
      mean model residual within 0.5 mm.

PMID- 29350192
TI  - Size-dependent Young's modulus in ZnO nanowires with strong surface atomic bonds.
AB  - The mechanical properties of size-dependent nanowires are important in nano
      electro-mechanical systems (NEMSs), and have attracted much research interest.
      Characterization of the size effect of nanowires in atmosphere directly to
      broaden their practical application instead of just in high vacuum situations, as
      reported previously, is desperately needed. In this study, we systematically
      studied the Young's modulus of vertical ZnO nanowires in atmosphere. The
      diameters ranged from 48 nm to 239 nm with a resonance method using non-contact
      atomic force microscopy. The values of Young's modulus in atmosphere present
      extremely strong increasing tendency with decreasing diameter of nanowire due to
      stronger surface atomic bonds compared with that in vacuum. A core-shell model
      for nanowires is proposed to explore the Young's modulus enhancement in
      atmosphere, which is correlated with atoms of oxygen occurring near the nanowire
      surface. The modified model is more accurate for analyzing the mechanical
      behavior of nanowires in atmosphere compared with the model in vacuum.
      Furthermore, it is possible to use this characterization method to measure the
      size-related elastic properties of similar wire-sharp nanomaterials in atmosphere
      and estimate the corresponding mechanical behavior. The study of the size
      dependent Young's modulus in ZnO nanowires in atmosphere will improve the
      understanding of the mechanical properties of nanomaterials as well as providing
      guidance for applications in NEMSs, nanogenerators, biosensors and other related
      areas.

PMID- 29350193
TI  - Layer structured bismuth selenides Bi2Se3 and Bi3Se4 for high energy and flexible
      all-solid-state micro-supercapacitors.
AB  - In this work, bismuth selenides (Bi2Se3 and Bi3Se4), both of which have a layered
      rhombohedral crystal structure, have been found to be useful as electrode
      materials for supercapacitor applications. In a liquid electrolyte system (6M
      KOH), Bi2Se3 nanoplates exhibit much better performance as an electrode material
      than Bi3Se4 nanoparticles do, delivering a higher specific capacitance (272.9 F g
      1) than that of Bi3Se4 (193.6 F g-1) at 5 mV s-1. This result may be attributed
      to the fact that Bi2Se3 nanoplates possess more active electrochemical surfaces
      for the reversible surface redox reactions owing to their planar quintuple
      stacked layers (septuple layers for Bi3Se4). To meet the demands of electronic
      skin, we used a novel flexible annular interdigital structure electrode to
      support the all-solid-state micro-supercapacitors (AMSCs). The Bi2Se3 AMSC device
      delivers a much better supercapacitor performance, exhibits a large stack
      capacitance of 89.5 F cm-3 at 20 mV s-1 (Bi3Se4: 79.1 F cm-3), a high energy
      density of 17.9 mWh cm-3 and a high power density of 18.9 W cm-3. The bismuth
      selenides also exhibit good cycle stability, with 95.5% retention after 1000 c
      for Bi2Se3 (Bi3Se4:90.3%). Clearly, Bi2Se3 nanoplates can be promising electrode
      materials for flexible annular interdigital AMSCs.

PMID- 29350194
TI  - Detection rate of fetal distress using contraction-dependent fetal heart rate
      variability analysis.
AB  - OBJECTIVE: Monitoring of the fetal condition during labor is currently performed
      by cardiotocograpy (CTG). Despite the use of CTG in clinical practice, CTG
      interpretation suffers from a high inter- and intra-observer variability and a
      low specificity. In addition to CTG, analysis of fetal heart rate variability
      (HRV) has been shown to provide information on fetal distress. However, fetal HRV
      can be strongly influenced by uterine contractions, particularly during the
      second stage of labor. Therefore, the aim of this study is to examine if
      distinguishing contractions from rest periods can improve the detection rate of
      HRV features for fetal distress during the second stage of labor. APPROACH: We
      used a dataset of 100 recordings, containing 20 cases of fetuses with adverse
      outcome. The most informative HRV features were selected by a genetic algorithm
      and classification performance was evaluated using support vector machines. MAIN
      RESULTS: Classification performance of fetal heart rate segments closest to birth
      improved from a geometric mean of 70% to 79%. If the classifier was used to
      indicate fetal distress over time, the geometric mean at 15 minutes before birth
      improved from 60% to 72%. SIGNIFICANCE: Our results show that combining
      contraction-dependent HRV features with HRV features calculated over the entire
      fetal heart rate signal improves the detection rate of fetal distress.

PMID- 29350195
TI  - Design and fabrication of a multifocal bionic compound eye for imaging.
AB  - Miniaturized bionic compound eyes featured with multi-aperture imaging have
      potential applications in the areas of micro opto-electro-mechanical-system. In
      this manuscript, we present a novel structure of the bionic compound eye with
      multiple focal lengths consists of an array of individual lenses with 1000 um
      diameter. The simulation results of the designed multifocal bionic compound eye
      (MBCE) with two focal lengths of 190 mm and 44.4 mm demonstrate excellent two
      order focusing abilities. Moving mask exposure technology was used to fabricate
      the designed MBCE with the corresponding imaging experiments conducted to
      validate the two-order imaging ability of the fabricated MBCE. Experimental
      results revealed that the developed structure has potential applications in
      diverse optical imaging systems such as three-dimensional imaging and real-time
      detection of unconfined or fluctuating targets.

PMID- 29350196
TI  - Estimation and correction of produced light from prompt gamma photons on
      luminescence imaging of water for proton therapy dosimetry.
AB  - Although the luminescence images of water during proton-beam irradiation using a
      cooled charge-coupled device camera showed almost the same ranges of proton beams
      as those measured by an ionization chamber, the depth profiles showed lower Bragg
      peak intensities than those measured by an ionization chamber. In addition, a
      broad optical baseline signal was observed in depths that exceed the depth of the
      Bragg peak. We hypothesize that this broad baseline signal originates from the
      interaction of proton-induced prompt gamma photons with water. These prompt gamma
      photons interact with water to form high-energy Compton electrons, which may
      cause luminescence or Cherenkov emission from depths exceeding the location of
      the Bragg peak. To clarify this idea, we measured the luminescence images of
      water during the irradiations of protons in water with minimized parallax errors,
      and also simulated the produced light by the interactions of prompt gamma photons
      with water. We corrected the measured depth profiles of the luminescence images
      by subtracting the simulated distributions of the produced light by the
      interactions of prompt gamma photons in water. Corrections were also conducted
      using the estimated depth profiles of the light of the prompt gamma photons, as
      obtained from the off-beam areas of the luminescence images of water. With these
      corrections, we successfully obtained depth profiles that have almost identical
      distributions as the simulated dose distributions for protons. The percentage
      relative height of the Bragg peak with corrections to that of the simulation data
      increased to 94% from 80% without correction. Also, the percentage relative
      offset heights of the deeper part of the Bragg peak with corrections decreased to
      0.2%-0.4% from 4% without correction. These results indicate that the
      luminescence imaging of water has potential for the dose distribution
      measurements for proton therapy dosimetry.

PMID- 29350197
TI  - A 3D correction method for predicting the readings of a PinPoint chamber on the
      CyberKnife(r) M6TM machine.
AB  - The use of small fields in radiation therapy techniques has increased
      substantially in particular in stereotactic radiosurgery (SRS) and stereotactic
      body radiation therapy (SBRT). However, as field size reduces further still, the
      response of the detector changes more rapidly with field size, and the effects of
      measurement uncertainties become increasingly significant due to the lack of
      lateral charged particle equilibrium, spectral changes as a function of field
      size, detector choice, and subsequent perturbations of the charged particle
      fluence. This work presents a novel 3D dose volume-to-point correction method to
      predict the readings of a 0.015 cc PinPoint chamber (PTW 31014) for both small
      static-fields and composite-field dosimetry formed by fixed cones on the
      CyberKnife(r) M6TM machine. A 3D correction matrix is introduced to link the 3D
      dose distribution to the response of the PinPoint chamber in water. The
      parameters of the correction matrix are determined by modeling its 3D dose
      response in circular fields created using the 12 fixed cones (5 mm-60 mm) on a
      CyberKnife(r) M6TM machine. A penalized least-square optimization problem is
      defined by fitting the calculated detector reading to the experimental
      measurement data to generate the optimal correction matrix; the simulated
      annealing algorithm is used to solve the inverse optimization problem. All the
      experimental measurements are acquired for every 2 mm chamber shift in the
      horizontal planes for each field size. The 3D dose distributions for the
      measurements are calculated using the Monte Carlo calculation with the
      MultiPlan(r) treatment planning system (Accuray Inc., Sunnyvale, CA, USA). The
      performance evaluation of the 3D conversion matrix is carried out by comparing
      the predictions of the output factors (OFs), off-axis ratios (OARs) and
      percentage depth dose (PDD) data to the experimental measurement data. The
      discrepancy of the measurement and the prediction data for composite fields is
      also performed for clinical SRS plans. The optimization algorithm used for
      generating the optimal correction factors is stable, and the resulting correction
      factors were smooth in the spatial domain. The measurement and prediction of OFs
      agree closely with percentage differences of less than 1.9% for all the 12 cones.
      The discrepancies between the prediction and the measurement PDD readings at 50
      mm and 80 mm depth are 1.7% and 1.9%, respectively. The percentage differences of
      OARs between measurement and prediction data are less than 2% in the low dose
      gradient region, and 2%/1 mm discrepancies are observed within the high dose
      gradient regions. The differences between the measurement and prediction data for
      all the CyberKnife based SRS plans are less than 1%. These results demonstrate
      the existence and efficiency of the novel 3D correction method for small field
      dosimetry. The 3D correction matrix links the 3D dose distribution and the
      reading of the PinPoint chamber. The comparison between the predicted reading and
      the measurement data for static small fields (OFs, OARs and PDDs) yield
      discrepancies within 2% for low dose gradient regions and 2%/1 mm for high dose
      gradient regions; the discrepancies between the predicted and the measurement
      data are less than 1% for all the SRS plans. The 3D correction method provides an
      access to evaluate the clinical measurement data and can be applied to non
      standard composite fields intensity modulated radiation therapy point dose
      verification.

PMID- 29350198
TI  - Preparation of sub 3 nm copper nanoparticles by microwave irradiation in the
      presence of triethylene tetramin.
AB  - The preparation of sub 3 nm copper nanoparticles (CuNPs) in ethylene glycol (EG)
      using triethylene tetramine (TETA) as chelating and reducing agents via a rapid
      microwave (MW) irradiation is reported. The sub 3 nm CuNPs after MW irradiation
      are clearly seen from the electronic micrographs. The firm chelation of Cu2+ by
      TETA is illustrated by the dark blue color of Cu2+/TETA/EG solution and the redox
      reaction is confirmed by the appearance of red color of the mixtures. The optimal
      mole ratio of TETA/Cu 2+ is found to be 2.5/1 for preparing sub 3 nm CuNPs under
      the MW irradiation, operated at 800 W for 1 min. The plasmonic absorption lambda
      max demonstrated in UV-vis spectra are found to close to 200 nm for sub 3 nm
      CuNPs, comparing to 500 ~ 600 nm for regular, larger CuNPs. The extremely low Tm
      around 30  degrees C and the fusion/recrystallization sequence of sub 3 nm CuNPs
      can be directly measured by their differential scanning calorimetry thermograms.

PMID- 29350199
TI  - Cortical visual prostheses: from microstimulation to functional percept.
AB  - Cortical visual prostheses are intended to restore vision by targeted electrical
      stimulation of the visual cortex. The perception of spots of light, called
      phosphenes, resulting from microstimulation of the visual pathway, suggests the
      possibility of creating meaningful percept made of phosphenes. However, to date
      electrical stimulation of V1 has still not resulted in perception of phosphenated
      images that goes beyond punctate spots of light. In this review, we summarize the
      clinical and experimental progress that has been made in generating phosphenes
      and modulating their associated perceptual characteristics in human and macaque
      primary visual cortex (V1). We focus specifically on the effects of different
      microstimulation parameters on perception and we analyse key challenges facing
      the generation of meaningful artificial percepts. Finally, we propose solutions
      to these challenges based on the application of supervised learning of population
      codes for spatial stimulation of visual cortex.

PMID- 29350200
TI  - Leaf-templated, microwell-integrated microfluidic chips for high-throughput cell
      experiments.
AB  - As an alternative to conventional cell culture and animal testing, an organ-on-a
      chip is applied to study the biological phenomena of organ development and
      disease, as well as the interactions between human tissues and external stimuli
      such as chemicals, forces and electricity. The pattern design of a microfluidic
      channel is one of the key approaches to regulate cell growth and differentiation,
      because these channels work as a crucial vasculature system to control the
      fluidic flow throughout the organ-on-a-chip device. In this study, we introduce a
      novel leaf-templated, microwell-integrated microfluidic chip for high-throughput
      cell experiments, consisting of a leaf-venation layer for fluent fluid flow, and
      a microwell-array layer for cell to reside. Computational fluid dynamics analysis
      was carried out to study the fluidic flow within leaf-venation network, which was
      further used to optimize the design of microwell arrays. A simple leaf-venation
      mold-based microreplication method was developed to transfer the intact native
      leaf venation network into leaf-venation layer and 3D printing technology was
      used to fabricate the microwell-array layer. The layers were then assembled and
      used for perfusion culture, showing that leaf-templated microfluidic channels
      provided a sufficient culture medium for cells within each microwell. These
      results indicate a novel and effective strategy to generate a biomimetic
      microfluidic chip with an effective vascular transport system for high-throughput
      cell experiments.

PMID- 29350201
TI  - Moth-eye mimetic cytocompatible bactericidal nanotopography: a convergent design.
AB  - The rapid emergence of antibiotic resistant bacteria has prompted the need for
      radically different approaches to combat bacterial infections. Among these,
      bioinspired surface topographies have emerged as an effective sustainable
      strategy to deter bacterial infection. This study demonstrates the bactericidal
      activity and cytocompatibility of the moth-eye mimetic topography produced by
      thermal polymer nanoimprinting. The moth-eye topography was found to have
      bactericidal capabilities against Gram negative and Gram positive bacteria.
      Electron microscopy imaging revealed the bactericidal effect caused by mechanical
      rupture of the bacteria wall inflicted by the topography on the adhered cells.
      The cytocompatibility of the surfaces was evidenced by assessing the
      proliferation and morphology of keratinocytes cultured on the nanotopography. The
      technology meets important needs in medical implant technology for materials that
      not only have good biocompatibility but also antibacterial properties for
      reducing the risk of infections and related health complications.

PMID- 29350202
TI  - Observation of low temperature metastable states in complex CaMn7O12.
AB  - The low temperature magnetic behaviour of the multiferroic quadruple perovskite
      CaMn7O12 is investigated. The magneto-caloric effect in this material is
      presented for the first time. Along with the established magnetic transitions, T
      N1 ~ 90 K and T N2 ~ 45 K, an anomaly at 20 K is observed in our dc
      magnetization, ac susceptibility and dielectric measurements; below which, an
      inverse magnetocaloric effect is also observed in our  -DeltaS M (T) plots. The
      neutron scattering measurements show minimal change between 10 K and 30 K in
      static correlations, but a clear change in energy and linewidth of the magnetic
      excitations is evident. The results suggest that only dynamic correlations change
      across T M ~ 20 K. The existence of multiple magnetic interactions below 45 K,
      with significant coupling between them, is demonstrated using an Arrott plot
      analysis of our magnetic data. Compatible conclusions are drawn from
      magnetocaloric plots. The peak change in isothermal magnetic entropy (-DeltaS M)
      is 1.3 JK-1 kg-1 and the value of refrigeration capacity in CaMn7O12 is 34.5 J .
      kg-1 at 7 T.

PMID- 29350203
TI  - Subungual exostosis on index finger in a child.

PMID- 29350204
TI  - PubMed indexing: Misconceptions.

PMID- 29350205
TI  - Silymarin: An interesting modality in dermatological therapeutics.

PMID- 29350206
TI  - Commentary on "Altered PIWI-LIKE 1 and PIWI-LIKE 2 mRNA expression in ejaculated
      spermatozoa of men with impaired sperm characteristics".

PMID- 29350207
TI  - Association between CYP2C19 and ABCB1 polymorphisms and clopidogrel resistance in
      clopidogrel-treated Chinese patients.
AB  - OBJECTIVE: To investigate the association between CYP2C19 and ABCB1 polymorphisms
      and clopidogrel resistance (CR) in patients with cardiovascular disease in
      Beijing district. METHODS: In total, 325 patients were enrolled in the study,
      including 101 experimental group patients and 224 control group patients. The
      experimental group was divided into CR group (n=30) and non-CR group (n=71)
      according to the adenosine diphosphate (ADP)-induced platelet inhibition rate in
      thromboelastography (TEG) (ADP-induced platelet inhibition rate of <30% was
      defined as CR and rate of 30%-100% was defined as non-CR). Genotypes, including
      CYP2C19*2, CYP2C19*3, CYP2C19*4, CYP2C19*5, CYP2C19*17, and ABCB1, were
      determined using time-of-flight mass spectrometry (Clin-TOF) and Sanger
      sequencing in all patients. RESULTS: In the experimental group, carriers of
      CYP2C19 heterozygous (*1/*2, n=46; *1/*3, n=7), and mutation homozygous (*2/*2,
      n=7; *2/*3, n=3; *3/*3, n=0) genotypes showed significantly lower ADP-induced
      platelet inhibition rates than noncarriers (*1/*1, n=38; p=0.035 and 0.001,
      respectively); the carriage of mutant CYP2C19*2 or *3 allele was significantly
      associated with an increased risk of CR. In contrast, carriers of ABCB1
      heterozygous (TC, n=50) showed significantly lower ADP-induced platelet
      inhibition rates than noncarriers (CC, n=39, p=0.097), and there was no
      significant correlation between ABCB1 genotypes and higher CR risk. CONCLUSION:
      The carriage of CYP2C19*2 or *3 mutant allele was significantly associated with
      attenuated platelet response to clopidogrel and increased CR risk. The carriage
      of ABCB1 mutant allele was not significantly associated with CR risk.

PMID- 29350208
TI  - Protective effect of paracetamol in doxorubicin-induced cardiotoxicity in
      ischemia/reperfused isolated rat heart.
AB  - OBJECTIVE: Doxorubicin (DOX) induces cardiac dysfunction. Paracetamol (APAP) has
      also been established as an effective cardioprotective agent during
      ischemia/reperfusion. Therefore, this study aims to evaluate the effect of APAP
      on DOX-induced cardiotoxicity in ischemia/reperfused isolated rat heart. METHODS:
      A total of 36 rats were equally divided into four groups: control, DOX (30 min,
      20 uM DOX perfusion), APAP (15 min before and after ischemia, 0.35 mM APAP
      perfusion), and DOX+APAP (perfused with the same protocol in DOX and APAP
      groups). The isolated hearts were perfused according to the Langendorff method.
      Cardiac parameters, including left ventricular developed pressure (LVDP), heart
      rate (HR), coronary flow (CF), and rate pressure product (RPP; LVDP*HR) were
      measured. Lactate dehydrogenase (LDH) concentration was also assessed. RESULTS:
      At the end of the baseline period, the RPP, HR, and CF values were lower in the
      DOX group than in the control group (p<0.01). Meanwhile, there were no
      significant differences between the values of cardiac function parameters in the
      DOX+APAP and control groups. In the reperfusion period, the RPP and CF values
      were significantly increased in the DOX+APAP group compared with the DOX group
      (p<0.05). Furthermore, the LDH concentration was decreased in the DOX+APAP group
      compared with the DOX group. CONCLUSION: APAP perfusion protected the hearts
      against DOX-induced cardiotoxicity in the baseline and ischemia/reperfusion
      conditions. These findings can be explained by the effect of APAP on antioxidant
      capacity and mitochondrial permeability transition pores.

PMID- 29350209
TI  - Molecular basis for CENP-N recognition of CENP-A nucleosome on the human
      kinetochore.

PMID- 29350210
TI  - Response to: Comment on "Differences in Ventilatory Threshold for Exercise
      Prescription in Outpatient Diabetic and Sarcopenic Obese Subjects".

PMID- 29350211
TI  - Correction: A niche that triggers aggressiveness within BRCA1-IRIS overexpressing
      triple negative tumors is supported by reciprocal interactions with the
      microenvironment.
AB  - [This corrects the article DOI: 10.18632/oncotarget.20892.].

PMID- 29350212
TI  - Defining System Boundaries of an Institution Nitrogen Footprint.
AB  - A nitrogen (N) footprint quantifies the amount of reactive nitrogen released to
      the environment and can be measured at different scales. The N footprint of a
      university includes activities and consumption within its geographic boundaries
      as well as activities that support the institution. Determining system bounds of
      an N footprint depends on the institution's mission and provides a common
      baseline for comparison. A comparison of three scopes of the N footprint, which
      describe how emissions are directly related to an institution's activities, was
      conducted for seven institutions. Scopes follow the established definition for
      the carbon footprint. In this article, the authors propose a new system bounds
      definition (core campus versus adjunct). Two case studies were explored: how the
      N footprint of Dickinson College changed with air travel, and how the N footprint
      of the Marine Biological Laboratory changed with scientific research. Of the
      three scopes, scope 3 was consistently the largest proportion of the N footprint
      for all seven institutions. The core campus activities of Dickinson College made
      up 99 percent of its N footprint, with air travel making up the remaining 1
      percent. The Marine Biological Laboratory's core campus activities made up 51
      percent of its N footprint and the scientific research made up the remaining 49
      percent. Institutions should define system bounds based on their mission and stay
      consistent with their boundaries following the baseline year. The core campus
      footprint could be used to compare institution footprints using consistent system
      bounds. How institutions define their boundaries will impact the recorded amount
      of nitrogen as well as how the institution will set reduction strategies.

PMID- 29350213
TI  - Erratum.
AB  - [This corrects the article DOI: 10.1177/2382120516684829.].

PMID- 29350214
TI  - Erratum.
AB  - [This corrects the article DOI: 10.1177/2050313X17744072.].

PMID- 29350215
TI  - Validation of prediction models: examining temporal and geographic stability of
      baseline risk and estimated covariate effects.
AB  - Background: Stability in baseline risk and estimated predictor effects both
      geographically and temporally is a desirable property of clinical prediction
      models. However, this issue has received little attention in the methodological
      literature. Our objective was to examine methods for assessing temporal and
      geographic heterogeneity in baseline risk and predictor effects in prediction
      models. Methods: We studied 14,857 patients hospitalized with heart failure at 90
      hospitals in Ontario, Canada, in two time periods. We focussed on geographic and
      temporal variation in baseline risk (intercept) and predictor effects (regression
      coefficients) of the EFFECT-HF mortality model for predicting 1-year mortality in
      patients hospitalized for heart failure. We used random effects logistic
      regression models for the 14,857 patients. Results: The baseline risk of
      mortality displayed moderate geographic variation, with the hospital-specific
      probability of 1-year mortality for a reference patient lying between 0.168 and
      0.290 for 95% of hospitals. Furthermore, the odds of death were 11% lower in the
      second period than in the first period. However, we found minimal geographic or
      temporal variation in predictor effects. Among 11 tests of differences in time
      for predictor variables, only one had a modestly significant P value (0.03).
      Conclusions: This study illustrates how temporal and geographic heterogeneity of
      prediction models can be assessed in settings with a large sample of patients
      from a large number of centers at different time periods.

PMID- 29350216
TI  - The Nitrogen Footprint Tool Network: A Multi-Institution Program To Reduce
      Nitrogen Pollution.
AB  - Anthropogenic sources of reactive nitrogen have local and global impacts on air
      and water quality and detrimental effects on human and ecosystem health. This
      article uses the Nitrogen Footprint Tool (NFT) to determine the amount of
      nitrogen (N) released as a result of institutional consumption. The sectors
      accounted for include food (consumption and upstream production), energy,
      transportation, fertilizer, research animals, and agricultural research. The NFT
      is then used for scenario analysis to manage and track reductions, which are
      driven by the consumption behaviors of both the institution itself and its
      constituent individuals. In this article, the first seven completed institution
      nitrogen footprint results are presented. The Nitrogen Footprint Tool Network
      aims to develop footprints for many institutions to encourage widespread upper
      level management strategies that will create significant reductions in reactive
      nitrogen released to the environment. Energy use and food purchases are the two
      largest sectors contributing to institution nitrogen footprints. Ongoing efforts
      by institutions to reduce greenhouse gas emissions also help to reduce the
      nitrogen footprint, but the impact of food production on nitrogen pollution has
      not been directly addressed by the higher education sustainability community. The
      Nitrogen Footprint Tool Network found that institutions could reduce their
      nitrogen footprints by optimizing food purchasing to reduce consumption of animal
      products and minimize food waste, as well as by reducing dependence on fossil
      fuels for energy.

PMID- 29350217
TI  - An Integrated Tool for Calculating and Reducing Institution Carbon and Nitrogen
      Footprints.
AB  - The development of nitrogen footprint tools has allowed a range of entities to
      calculate and reduce their contribution to nitrogen pollution, but these tools
      represent just one aspect of environmental pollution. For example, institutions
      have been calculating their carbon footprints to track and manage their
      greenhouse gas emissions for over a decade. This article introduces an integrated
      tool that institutions can use to calculate, track, and manage their nitrogen and
      carbon footprints together. It presents the methodology for the combined tool,
      describes several metrics for comparing institution nitrogen and carbon footprint
      results, and discusses management strategies that reduce both the nitrogen and
      carbon footprints. The data requirements for the two tools overlap substantially,
      although integrating the two tools does necessitate the calculation of the carbon
      footprint of food. Comparison results for five institutions suggest that the
      institution nitrogen and carbon footprints correlate strongly, especially in the
      utilities and food sectors. Scenario analyses indicate benefits to both
      footprints from a range of utilities and food footprint reduction strategies.
      Integrating these two footprints into a single tool will account for a broader
      range of environmental impacts, reduce data entry and analysis, and promote
      integrated management of institutional sustainability.

PMID- 29350218
TI  - Comparing Institution Nitrogen Footprints: Metrics for Assessing and Tracking
      Environmental Impact.
AB  - When multiple institutions with strong sustainability initiatives use a new
      environmental impact assessment tool, there is an impulse to compare. The first
      seven institutions to calculate nitrogen footprints using the Nitrogen Footprint
      Tool have worked collaboratively to improve calculation methods, share resources,
      and suggest methods for reducing their footprints. This article compares those
      seven institutions' results to reveal the common and unique drivers of
      institution nitrogen footprints. The footprints were compared by scope and
      sector, and the results were normalized by multiple factors (e.g., population,
      amount of food served). The comparisons found many consistencies across the
      footprints, including the large contribution of food. The comparisons identified
      metrics that could be used to track progress, such as an overall indicator for
      the nitrogen sustainability of food purchases. The comparisons also pointed to
      differences in system bounds of the calculations, which are important to
      standardize when comparing across institutions. The footprints were influenced by
      factors both within and outside of the institutions' ability to control, such as
      size, location, population, and campus use. However, these comparisons also point
      to a pathway forward for standardizing nitrogen footprint tool calculations,
      identifying metrics that can be used to track progress, and determining a
      sustainable institution nitrogen footprint.

PMID- 29350219
TI  - Reducing the Nitrogen Footprint of a Small Residential College.
AB  - The release of reactive nitrogen contributes to its accumulation in the
      environment, causing a variety of harmful effects. To measure Dickinson College's
      contribution to nitrogen pollution, and quantify the potential to reduce its
      contribution, we calculated the college's nitrogen footprint and simulated the
      effects of selected nitrogen mitigation measures. The analysis was obtained using
      the Nitrogen Footprint Tool, developed at the University of Virginia. Food
      production is by far the largest contributor to Dickinson's footprint, followed
      by heat and power. Transportation, sewage, and groundskeeping contribute
      relatively small amounts. Breaking food down into different food categories, meat
      and fish is the largest source of nitrogen, accounting for two-thirds of the food
      footprint. Simulations of individual mitigation measures showed that measures
      targeting food are the most impactful for reducing the college's nitrogen
      footprint. Two policy scenarios that combine multiple measures, one representing
      moderate action and the other more aggressive action, were also analyzed. They
      are projected to reduce Dickinson's footprint by roughly 15 and 25 percent,
      respectively, while reducing operating costs. Achieving these reductions would
      require substantial changes in dietary choices by members of the campus
      community.

PMID- 29350220
TI  - Nephrotic syndrome in primary myelofibrosis with renal extramedullary
      hematopoiesis and glomerulopathy in the JAK inhibitor era.
AB  - Primary myelofibrosis (PMF) is an uncommon form of myeloproliferative neoplasm
      (MPN) characterized by a proliferation of predominantly megakaryocytes and
      granulocytes in the bone marrow that, in fully-developed disease, is associated
      with reactive deposition of fibrous connective tissue, extramedullary
      hematopoiesis (EMH), and splenomegaly. Kidney involvement is rare and clinically
      presents with proteinuria, nephrotic syndrome, and renal insufficiency. Renal
      damage can be due to EMH and glomerulopathy. Renal EMH presents three patterns:
      infiltration of the interstitium with possible renal failure caused by functional
      damage of parenchyma and vessels, infiltration of capsule and pericapsular
      adipose tissue, and sclerosing mass-like lesions that can cause hydronephrosis
      and hydroureter with obstructive uropathy and renal failure. Glomerulopathy
      associated with PMF is rarely described, ranging from 1 month to 18 years from
      diagnosis of the neoplasm to renal biopsy. It is characterized by expansion and
      hypercellularity mesangial, segmental sclerosis, features of chronic thrombotic
      microangiopathy (TMA), and intracapillary hematopoietic cells infiltrating in
      absence of immune-mediated glomerulonephritis. We present a nephrotic syndrome in
      PMF-related glomerulopathy, associated with EMH, without renal failure, in a
      patient under treatment for 2 years with JAK2 inhibitor ruxolitinib. Despite
      treatment, the patient died 7 months after renal biopsy. Nephrologists still know
      very little about this topic and there is no homogeneous data about incidence,
      pathogenesis, and optimal treatment of this poor prognostic PMF-associated
      nephrotic syndrome. We focus on data in the literature in the hope of stimulating
      hematologists, nephrologists, pathologists to future studies about the natural
      history of renal involvement, useful for optimal management of this rare
      pathology.

PMID- 29350221
TI  - Assessing the Social and Environmental Costs of Institution Nitrogen Footprints.
AB  - This article estimates the damage costs associated with the institutional
      nitrogen (N) footprint and explores how this information could be used to create
      more sustainable institutions. Potential damages associated with the release of
      nitrogen oxides (NOx), ammonia (NH3), and nitrous oxide (N2O) to air and release
      of nitrogen to water were estimated using existing values and a cost per unit of
      nitrogen approach. These damage cost values were then applied to two
      universities. Annual potential damage costs to human health, agriculture, and
      natural ecosystems associated with the N footprint of institutions were $11.0
      million (2014) at the University of Virginia (UVA) and $3.04 million at the
      University of New Hampshire (UNH). Costs associated with the release of nitrogen
      oxides to human health, in particular the use of coal-derived energy, were the
      largest component of damage at UVA. At UNH the energy N footprint is much lower
      because of a landfill cogeneration source, and thus the majority of damages were
      associated with food production. Annual damages associated with release of
      nitrogen from food production were very similar at the two universities ($1.80
      million vs. $1.66 million at UVA and UNH, respectively). These damages also have
      implications for the extent and scale at which the damages are felt. For example,
      impacts to human health from energy and transportation are generally larger near
      the power plants and roads, while impacts from food production can be distant
      from the campus. Making this information available to institutions and
      communities can improve their understanding of the damages associated with the
      different nitrogen forms and sources, and inform decisions about nitrogen
      reduction strategies.

PMID- 29350222
TI  - A Prescription for Note Bloat: An Effective Progress Note Template.
AB  - BACKGROUND: United States hospitals have widely adopted electronic health records
      (EHRs). Despite the potential for EHRs to increase efficiency, there is concern
      that documentation quality has suffered. OBJECTIVE: To examine the impact of an
      educational session bundled with a progress note template on note quality,
      length, and timeliness. DESIGN: A multicenter, nonrandomized prospective trial.
      SETTING: Four academic hospitals across the United States. PARTICIPANTS: Intern
      physicians on inpatient internal medicine rotations at participating hospitals.
      INTERVENTION: A task force delivered a lecture on current issues with
      documentation and suggested that interns use a newly designed best practice
      progress note template when writing daily progress notes. MEASUREMENTS: Note
      quality was rated using a tool designed by the task force comprising a general
      impression score, the validated Physician Documentation Quality Instrument, 9
      item version (PDQI-9), and a competency questionnaire. Reviewers documented
      number of lines per note and time signed. RESULTS: Two hundred preintervention
      and 199 postintervention notes were collected. Seventy percent of
      postintervention notes used the template. Significant improvements were seen in
      the general impression score, all domains of the PDQI-9, and multiple competency
      items, including documentation of only relevant data, discussion of a discharge
      plan, and being concise while adequately complete. Notes had approximately 25%
      fewer lines and were signed on average 1.3 hours earlier in the day. CONCLUSIONS:
      The bundled intervention for progress notes significantly improved the quality,
      decreased the length, and resulted in earlier note completion across 4 academic
      medical centers.

PMID- 29350223
TI  - What Is Career Success for Academic Hospitalists? A Qualitative Analysis of Early
      Career Faculty Perspectives.
AB  - BACKGROUND: Understanding the concept of career success is critical for hospital
      medicine groups seeking to create sustainably rewarding faculty positions.
      Conceptual models of career success describe both extrinsic (compensation and
      advancement) and intrinsic (career satisfaction and job satisfaction) domains.
      How hospitalists define career success for themselves is not well understood. In
      this study, we qualitatively explore perspectives on how early-career clinician
      educators define career success. METHODS: We developed a semistructured interview
      tool of open-ended questions validated by using cognitive interviewing.
      Transcribed interviews were conducted with 17 early-career academic hospitalists
      from 3 medical centers to thematic saturation. A mixed deductiveinductive,
      qualitative, analytic approach was used to code and map themes to the theoretical
      framework. RESULTS: The single most dominant theme participants described was
      "excitement about daily work," which mapped to the job satisfaction organizing
      theme. Participants frequently expressed the importance of "being respected and
      recognized" and "dissemination of work," which were within the career
      satisfaction organizing theme. The extrinsic organizing themes of advancement and
      compensation were described as less important contributors to an individual's
      sense of career success. Ambivalence toward the "academic value of clinical
      work," "scholarship," and especially "promotion" represented unexpected themes.
      CONCLUSIONS: The future of academic hospital medicine is predicated upon faculty
      finding career success. Clinician-educator hospitalists view some traditional
      markers of career advancement as relevant to success. However, early-career
      faculty question the importance of some traditional external markers to their
      personal definitions of success. This work suggests that the selfconcept of
      career success is complex and may not be captured by traditional academic metrics
      and milestones.

PMID- 29350225
TI  - Visible-light-induced multicomponent cascade cycloaddition involving N-propargyl
      aromatic amines, diaryliodonium salts and sulfur dioxide: rapid access to 3
      arylsulfonylquinolines.
AB  - A visible-light-induced, Eosin Y catalyzed three-component synthesis of 3
      arylsulfonylquinoline derivatives through N-propargyl aromatic amines,
      diaryliodonium salts and sulfur dioxide has been discovered. This transformation
      represents an efficient and attractive method for the straightforward synthesis
      of 3-arylsulfonylquinoline derivatives via the formation of C-S bonds and
      quinolines in one step. In addition, it exhibits good substrate scope and
      functional group tolerance. The use of easy-to-handle diaryliodonium salts,
      sulfur dioxide sources and the cheap photocatalyst Eosin Y together with facile
      operation at room temperature makes this protocol very practical.

PMID- 29350226
TI  - The ortho-benzyne cation is not planar.
AB  - A recent review on the photoionisation of the C6H4 isomer ortho-benzyne suggests
      that bands reported in earlier photoelectron spectra might be due to side
      products or contaminations, while computations raise doubts, whether the cation
      has a planar geometry. We therefore reinvestigate the photoionisation of ortho
      benzyne, generated by pyrolysis from benzocyclobutenedione, by photoion mass
      selected threshold photoelectron (ms-TPE) spectroscopy using synchrotron
      radiation. The experiments are accompanied by a theoretical study that
      investigates the structure of the ortho-benzyne cation systematically as a
      function of the computational method, up to CASPT2(11,14) ab initio computations.
      Our study leads to a re-evaluation of the ionisation energy of ortho-benzyne. It
      reveals that the ortho-benzyne cation has indeed a twisted C2 geometry rather
      than a C2v structure. A vertical ionisation energy IEvert of 9.77 eV and an
      adiabatic ionisation energy of IEad = 9.56 eV are computed for ortho-benzyne. A
      Franck-Condon simulation of the photoelectron spectrum based on the CASPT2
      results and including three electronic states of the cation is in agreement with
      the experiment and yields IEad = 9.51 eV (+50 meV/-100 meV). Since this value is
      in contrast with previous work, the ionisation energy has to be revised based on
      our study. Computational methods based on density functional theory give a
      reasonable description of the cationic ground state, but fail for the
      corresponding excited electronic states that are indispensible for a proper
      assignment of the photoelectron spectrum.

PMID- 29350228
TI  - Correction: Films of bacteria at interfaces: three stages of behaviour.
AB  - Correction for 'Films of bacteria at interfaces: three stages of behaviour' by
      Liana Vaccari et al., Soft Matter, 2015, 11, 6062-6074.

PMID- 29350227
TI  - Albusnodin: an acetylated lasso peptide from Streptomyces albus.
AB  - We describe a lasso peptide, albusnodin, that is post-translationally modified
      with an acetyl group, the first example of a lasso peptide with this
      modification. Using heterologous expression, we further show that the
      acetyltransferase colocalized with the albusnodin gene cluster is required for
      the biosynthesis of this lasso peptide. This type of lasso peptide is widespread
      in Actinobacteria with 44 examples found in currently sequenced genomes.

PMID- 29350229
TI  - Aggregate evolution in aqueous solutions of a Gemini surfactant derived from
      dehydroabietic acid.
AB  - Innovations in surfactant structure are a feasible way to probe molecular self
      assembly principles. Herein, the solution behaviour of a newly synthesized Gemini
      surfactant derived from dehydroabietic acid, abbreviated R-(EO)-E-R, was
      investigated using surface tension, fluorescence, isothermal titration
      calorimetry (ITC), rheology, freeze-fracture transmission electron microscopy (FF
      TEM) and cryogenic transmission electron microscopy (cryo-TEM) methods. R-(EO)-E
      R has two large, rigid hydrophobic groups. At low concentrations, R-(EO)-E-R
      forms micelles with an aggregation number of approximately 10, which is smaller
      than those of Gemini surfactants containing flexible alkyl tails. In addition,
      the micellization process is less exothermic because of the rigidity of the
      hydrophobic portions. As the concentration increases, R-(EO)-E-R without any
      additives forms wormlike micelles, endowing the solution with an obvious
      viscoelasticity. Further increases in the concentration lead to the coexistence
      of single-walled vesicles, double-walled vesicles and rarely observed long,
      tubular vesicles. This behaviour is attributed to the two large, rigid
      hydrophobic groups of R-(EO)-E-R, which increase the density of the hydrophobic
      portion around the ionic head groups and facilitate the formation of aggregates
      with lower curvatures and asymmetric morphology. Surfactants containing rigid
      hydrophobic portions are expected to result in more delicate, self-assembled
      morphologies with broad applications.

PMID- 29350230
TI  - Selective growth of two-dimensional phosphorene on catalyst surface.
AB  - Although the study of black phosphorene (BP) and its isomers has attracted
      enormous attention, the method of synthesizing high-quality samples in a large
      area is still pending. Here we explore the potential of using the chemical vapor
      deposition method to synthesize large-area two-dimensional (2D) phosphorene films
      on metal surfaces. Our ab initio calculations show that BP can be synthesized by
      using tin (Sn) as a catalyst, while one of its isomers, blue phosphorene (BLP),
      is very possible to be synthesized by using most other metals, such as Ag and Au.
      Besides, our study also suggests that the large binding energy between the 2D
      phosphorene and the active metal substrate may prohibit the exfoliation of the 2D
      phosphorene for real applications and, therefore, tin, silver and gold are
      predicted to be the most suitable catalysts for the synthesis of BP and BLP.

PMID- 29350231
TI  - Tuning the sensitivity of lanthanide-activated NIR nanothermometers in the
      biological windows.
AB  - Lanthanide-activated SrF2 nanoparticles with a multishell architecture were
      investigated as optical thermometers in the biological windows. A ratiometric
      approach based on the relative changes in the intensities of different lanthanide
      (Nd3+ and Yb3+) NIR emissions was applied to investigate the thermometric
      properties of the nanoparticles. It was found that an appropriate doping with
      Er3+ ions can increase the thermometric properties of the Nd3+-Yb3+ coupled
      systems. In addition, a core containing Yb3+ and Tm3+ can generate light in the
      visible and UV regions upon near-infrared (NIR) laser excitation at 980 nm. The
      multishell structure combined with the rational choice of dopants proves to be
      particularly important to control and enhance the performance of nanoparticles as
      NIR nanothermometers.

PMID- 29350232
TI  - Impact of droplets on immiscible liquid films.
AB  - The impact of droplets on liquid films is a ubiquitous phenomenon not only in
      nature but also in many industrial applications. Compared to the widely-studied
      impact of droplets on films of identical fluids, the impact of droplets on
      immiscible films has received far less attention. In the present work, we show
      using high-speed imaging that immiscibility has a profound effect on the impact
      dynamics. The impact of a water droplet on an oil film leads to the formation of
      a compound crown followed by a central jet, whereas that of an oil droplet on a
      water film results in rapid spreading on the film surface driven by a large,
      positive spreading factor. In the former scenario, the central jet occurs due to
      the severe stretching of the droplet during the formation of the crown and then
      the retraction of the droplet by capillarity, which leads to the collision of
      fluid at the impact point. A model for the elongation dynamics of the central jet
      is proposed based on energy conservation. The effects of key parameters
      controlling the impact process are analysed, including the droplet Ohnesorge and
      Weber numbers, the viscosity ratio, and the dimensionless film thickness.
      Different impact outcomes are discussed, such as bouncing, deposition, and
      oscillation of the impact droplet, the formation and collapse of the compound
      crown, and the formation and tip-pinching of the central jet. This study not only
      provides physical insights into the impact dynamics, but could also facilitate
      the control and optimisation of the droplet impact process in a number of
      applications as highlighted herein.

PMID- 29350233
TI  - Stacking faults in Zr(Fe, Cr)2 Laves structured secondary phase particle in
      Zircaloy-4 alloy.
AB  - Stacking faults (SFs) in secondary phase particles (SPPs), which generally
      crystallize in the Laves phase in Zircaloy-4 (Zr-4) alloy, have been frequently
      observed by researchers. However, few investigations on the nano-scale structure
      of SFs have been carried out. In the present study, an SF containing C14
      structured SPP, which located at grain boundaries (GBs) in the alpha-Zr matrix,
      was chosen to be investigated, for its particular substructure as well as
      location, aiming to reveal the nature of the SFs in the SPPs in Zr-4 alloy. It
      was indicated that the SFs in the C14 structured SPP actually existed in the
      local C36 structured Laves phase, for their similarities in crystallography. The
      C14 -> C36 phase transformation, which was driven by synchroshearing among the
      (0001) basal planes, was the formation mechanism of the SFs in the SPPs. By
      analyzing the strained regions near the SPP, a model for understanding the
      driving force of the synchroshear was proposed: the interaction between SPP and
      GB resulted in the Zener pinning effect, leading to the shearing parallel to the
      (0001) basal planes of the C14 structured SPP, and the synchroshear was therefore
      activated.

PMID- 29350234
TI  - Dissociative electron attachment and anion-induced dimerization in pyruvic acid.
AB  - We report partial cross sections for the dissociative electron attachment to
      pyruvic acid. A rich fragmentation dynamics is observed. Electronic structure
      calculations facilitate the identification of complex rearrangement reactions
      that occur during the dissociation. Furthermore, a number of fragment anions
      produced at electron energies close to 0 eV are observed, that cannot originate
      from single electron-molecule collisions. We ascribe their production to
      secondary reactions of the transient anions with neutral molecules. Such
      reactions turn out to be unusually efficient; the most probable reason for this
      is that they proceed via the formation of a double-hydrogen-bonded complex
      followed by an ultrafast proton transfer between the reaction partners.

PMID- 29350235
TI  - Pressure induced photoluminescence modulation in a wide range and synthesis of
      monodispersed ternary AgCuS nanocrystal based on Ag2S nanocrystals.
AB  - Binary Ag2S nanocrystals (NCs) have many potential optical applications because
      of their low toxicity, narrow direct band gaps and near-infrared
      photoluminescence (PL) with high emission efficiency. However, due to its small
      exciton Bohr radius (2.2 nm), the PL spectra of Ag2S NCs can only be modulated
      below ~1200 nm with increasing particle size. Meanwhile, ternary silver copper
      chalcogenides (AgCuX, X = S, Se) have also attracted increased attention in
      recent years. Temperature-dependent structural phase transformation leads
      electrical transport to exhibit fascinating transitions between p and n type
      conduction, which makes AgCuS and AgCuSe ideal materials for diode or transistor
      devices. Nevertheless, the traditional method to synthesize these materials is
      mainly through melting the mixture of Ag, Cu and S/Se powder under extremely high
      reaction temperatures (973-1373 K) and long reaction time, forming a bulk
      product. Therefore, the synthesis of high quality monodispersed and size-tunable
      AgCuS or AgCuSe NCs is still a challenge. To address these issues, in this paper,
      we report using Ag2S NCs as a template, a method to synthesize monodispersed and
      size-tunable beta-AgCuS NCs via ion exchange and diffusion processes. Similarly,
      monodispersed beta-AgCuSe NCs were also synthesized by this simple and
      reproducible strategy. This synthetic method opens new avenues for investigating
      the size-, morphology- and temperature-dependent phase transitions of these
      ternary AgCuS and AgCuSe materials. Thus, the corresponding electrical transport
      between p and n type conduction can be studied in the future. Furthermore, we
      systematically investigated the pressure-dependent PL properties and band gap
      modulation of monodispersed Ag2S NCs using in situ high pressure PL and
      absorption spectroscopy. We found that the PL peak of 6.0 nm for Ag2S NCs could
      be easily adjusted from ~1200 to 1900 nm with increasing pressure from 0 to 5.1
      GPa, which greatly extends the wavelength range of the PL peak beyond that of
      other approaches.

PMID- 29350236
TI  - Dose optimization of total or partial skin electron irradiation by
      thermoluminescent dosimetry.
AB  - BACKGROUND: Due to the complex surface of the human body, total or partial skin
      irradiation using large electron fields is challenging. The aim of the present
      study was to quantify the magnitude of dose optimization required after the
      application of standard fields. METHODS: Total skin electron irradiation (TSEI)
      was applied using the Stanford technique with six dual-fields. Patients
      presenting with localized lesions were treated with partial skin electron
      irradiation (PSEI) using large electron fields, which were individually adapted.
      In order to verify and validate the dose distribution, in vivo dosimetry with
      thermoluminescent dosimeters (TLD) was performed during the first treatment
      fraction to detect potential dose heterogeneity and to allow for an individual
      dose optimization with adjustment of the monitor units (MU). RESULTS: Between
      1984 and 2017, a total of 58 patients were treated: 31 patients received TSEI
      using 12 treatment fields, while 27 patients underwent PSEI and were treated with
      4-8 treatment fields. After evaluation of the dosimetric results, an individual
      dose optimization was necessary in 21 patients. Of these, 7 patients received
      TSEI (7/31). Monitor units (MU) needed to be corrected by a mean value of 117 MU
      (+/-105, range 18-290) uniformly for all 12 treatment fields, corresponding to a
      mean relative change of 12% of the prescribed MU. In comparison, the other 14
      patients received PSEI (14/27) and the mean adjustment of monitor units was 282
      MU (+/-144, range 59-500) to single or multiple fields, corresponding to a mean
      relative change of 22% of the prescribed MU. A second dose optimization to obtain
      a satisfying dose at the prescription point was need in 5 patients. CONCLUSIONS:
      Thermoluminescent dosimetry allows an individual dose optimization in TSEI and
      PSEI to enable a reliable adjustment of the MUs to obtain the prescription dose.
      Especially in PSEI in vivo dosimetry is of fundamental importance.

PMID- 29350237
TI  - Long-term changes in multimodal intensive tinnitus therapy : A 5-year follow-up.
AB  - BACKGROUND: We present 5-year follow-up data for tinnitus-specific and comorbid
      depressive symptoms as well as stress-related outcome variables of an intensive
      multimodal 7-day tinnitus therapy. METHOD: Tinnitus burden (Tinnitus
      Questionnaire), stress (Perceived Stress Questionnaire), and depressive
      symptomatology (General Depression Scale) were measured at the 5-year follow-up
      after a multimodal intensive 7-day intervention. In all, 94 patients participated
      in the study. RESULTS: All outcome variables showed significant improvement at
      the end of the 7-day intensive treatment. These effects remained significant
      after 5 years. CONCLUSION: The results of the present study support the
      effectiveness of the 7-day multimodal intensive therapy for tinnitus.
      Posttreatment improvements were related to both tinnitus burden as well as stress
      and depressive symptoms and were maintained at the 5-year follow-up.

PMID- 29350238
TI  - [Female patient with pulsatile tinnitus].

PMID- 29350239
TI  - [The ABC guide for the treatment of posterior shoulder instability].
AB  - BACKGROUND: Posterior glenohumeral instability (PGHI) is an often unrecognized or
      misdiagnosed type of shoulder instability due to its heterogenic clinical and
      radiological presentation. CLASSIFICATION: The ABC classification for PGHI is
      based on the different pathomechanisms and recommended treatment standards and is
      therefore a guide to finding the correct diagnosis and therapy for affected
      patients. There are different types of PGHI: A (first time), B (dynamic), C
      (static). These groups are further classified based on pathomechanical
      principles: A1: subluxation, A2: dislocation; B1: functional, B2: structural; C1:
      constitutional, C2: acquired. THERAPY: In patients with type 1 PGHI (A1, B1, C1)
      conservative treatment is recommended while in patients with type 2 PGHI (A2, B2,
      C2) surgical treatment can be considered based on structural defects, clinical
      symptoms, chronicity, age, functional demand, and patient-specific health status.
      In addition it has to be considered, that there is the possibility of coexisting
      or overlapping subtypes as well as the chance of progression from one category
      into another over time.

PMID- 29350240
TI  - Left ventricular endocardial pacing for the critically ill.

PMID- 29350241
TI  - The airway occlusion pressure (P0.1) to monitor respiratory drive during
      mechanical ventilation: increasing awareness of a not-so-new problem.

PMID- 29350242
TI  - Is there a single non-painful procedure in the intensive care unit? It depends!

PMID- 29350243
TI  - Current opinions on nephrolithiasis associated with primary hyperparathyroidism.
AB  - Nephrolithiasis is a common urological disease and could be secondary to primary
      hyperparathyroidism (PHPT). PHPT is traditionally characterised with
      hypercalcaemia. Recently, a normocalcemic PHPT has been officially recognised at
      the International Workshops. Regarding this new phenotype, nephrolithiasis is
      frequently found in studies that evaluate low bone mass. However, until now, no
      study on aetiology of nephrolithiasis considered normocalcemic PHPT.
      Hypercalciuria related to PHPT is considered as an important risk factor of stone
      formation in hypercalcemic PHPT, but the precise relationships between
      hypercalcemic PHPT and nephrolithiasis and between normocalcemic PHPT and
      nephrolithiasis remain unclear. In patients with hypercalcemic PHPT, after a
      surgical cure of PHPT, the renal calcium excretion and stone recurrence rate
      reduce but remain higher above health controls. This finding implies that
      abnormalities not caused by PHPT also probably affect stone formation. According
      to the new guideline, the presence of stones indicates the need for
      parathyroidectomy in patients with either hypercalcemic or normocalcemic PHPT
      unless contraindications exist. Patients with contraindications for
      parathyroidectomy or those who do not want to receive parathyroidectomy should be
      monitored for signs of disease progression and given of medical management.
      Moreover, due to decreased but significantly higher frequency of nephrolithiasis
      above those of healthy controls, patients with nephrolithiasis associated with
      PHPT after parathyroidectomy still should be motivated to explore strategies to
      prevent stone occurrence.

PMID- 29350245
TI  - Chitinophaga caseinilytica sp. nov., a casein hydrolysing bacterium isolated from
      forest soil.
AB  - A novel casein hydrolysing bacterium designated strain S-52T was isolated from
      Kyonggi University forest soil. Cells were strictly aerobic, Gram stain-negative,
      oxidase- and catalase- positive, non-motile, non-spore-forming, rod-shaped, and
      golden-yellow-pigmented. Strain S-52T hydrolysed casein. It was able to grow at
      20-37  degrees C (optimum 25-32  degrees C), pH 6.5-11.0 (optimum 7-9.5), and at
      3% (w/v) NaCl concentration. Strain exhibits flexirubin-type pigments.
      Phylogenetic analysis based on 16S rRNA gene sequence revealed that strain S-52T
      formed a lineage within the genus Chitinophaga that was distinct from other
      species of the genus. Closest member was Chitinophaga barathri YLT18T (97.16% 16
      S rRNA gene sequence similarity). The major cellular fatty acids were iso-C15:0,
      C16:1omega5c, iso-C17:0 3-OH, and summed feature 3 (C16:1omega7c and/or C16:
      1omega6c). MK-7 was sole respiratory quinone. The major polar lipid was
      phosphatidylethanolamine. The DNA G + C content of strain S-52T was 48.8 mol%.
      DNA-DNA relatedness of strain S-52T with Chitinophaga barathri was 42.5%. On the
      basis of phenotypic, genotypic, phylogenetic, and chemotaxonomic
      characterization, S-52T represents a novel species in the genus Chitinophaga, for
      which the name Chitinophaga caseinilytica sp. nov. is proposed. The type strain
      is S-52T (= KEMB 9005-540T = KACC 19118T = NBRC 112679T).

PMID- 29350244
TI  - Autophagy-related (ATG) 11, ATG9 and the phosphatidylinositol 3-kinase control
      ATG2-mediated formation of autophagosomes in Arabidopsis.
AB  - KEY MESSAGE: Using quantitative assays for autophagy, we analyzed 4 classes of
      atg mutants, discovered new atg2 phenotypes and ATG gene interactions, and
      proposed a model of autophagosome formation in plants. Plant and other eukaryotic
      cells use autophagy to target cytoplasmic constituents for degradation in the
      vacuole. Autophagy is regulated and executed by a conserved set of proteins
      called autophagy-related (ATG). In Arabidopsis, several groups of ATG proteins
      have been characterized using genetic approaches. However, the genetic
      interactions between ATG genes have not been established and the relationship
      between different ATG groups in plants remains unclear. Here we analyzed atg2,
      atg7, atg9, and atg11 mutants and their double mutants at the physiological,
      biochemical, and subcellular levels. Involvement of phosphatidylinositol 3-kinase
      (PI3K) in autophagy was also tested using wortmannin, a PI3K inhibitor. Our
      mutant analysis using autophagy markers showed that atg7 and atg2 phenotypes are
      more severe than those of atg11 and atg9. Unlike other mutants, atg2 cells
      accumulated several autophagic vesicles that could not be delivered to the
      vacuole. Analysis of atg double mutants, combined with wortmannin treatment,
      indicated that ATG11, PI3K, and ATG9 act upstream of ATG2. Our data support a
      model in which plant ATG1 and PI3K complexes play a role in the initiation of
      autophagy, whereas ATG2 is involved in a later step during the biogenesis of
      autophagic vesicles.

PMID- 29350246
TI  - Data-Driven Quality Improvement Project to Increase the Value of the Congenital
      Echocardiographic Report.
AB  - Echocardiography is the primary diagnostic modality for congenital heart disease
      patients. The written report is used to communicate with the care team and
      organization is often divided into the body with detailed findings and the
      conclusions with important findings summarized. Strategies to increase workflow
      efficiency include batch writing of reports after performance of multiple
      echocardiograms and the use of report templates which may contribute to
      discrepancies within report leading to potential downstream medical errors. The
      aim of this project was to measure the rate of inconsistencies in the
      echocardiogram reports and through an iterative series of process improvement
      decrease this rate while maintaining sonographer efficiency and diagnostic
      accuracy. The discrepancy rate, diagnostic error rate, and sonographer
      productivity were collected one-year prior and during the iterative quality
      improvement process. The primary outcome and discrepancies in reports were
      determined by two reviewers: an experienced pediatric echocardiographic
      cardiologist and a senior sonographer. Minor discrepancies were defined as
      contradictions between the body and the conclusion of the report that were
      unlikely to affect patient care. Major discrepancies were defined as
      discrepancies between the body and the conclusion that had significant potential
      to affect patient care. Sonographer productivity was measured as studies per
      sonographer per month. Our primary intervention was to initiate a quarterly QI
      meeting and to decrease the batch writing of preliminary echocardiogram reports.
      No major discrepancies were identified pre- or post-intervention. The minor
      discrepancies decreased from 40.7 to 6%. Sonographer productivity was not
      significantly changed with a slight increase from 100 studies/sonographer/month
      during the baseline to 101 studies/sonographer/month during the intervention.
      There was no change in major or minor diagnostic error rate. Our quality
      improvement intervention increased the value of our reports by significantly
      decreasing minor discrepancies without negatively impacting sonographer
      productivity or diagnostic accuracy.

PMID- 29350247
TI  - Prolonged PR Interval at Birth Predicting the High Occurrence of Fatal
      Atrioventricular Block in Hypoplastic Left Heart Syndrome.
AB  - Infants with hypoplastic left heart syndrome (HLHS) are at high mortality
      especially when they are associated with bradyarrhythmias. However, the risk
      factor of developing high-grade atrioventricular block (HAVB) is still unclear.
      Seventy-three patients with HLHS in our institutions from 2002 to 2011 were
      enrolled. The survival rate was assessed by the anatomical types, treatments,
      occurrence of HAVB, severe tricuspid regurgitation (TR), and restrictive atrial
      septal defect (ASD) along with electrocardiogram findings at birth. There were 23
      (32%) cardiogenic and 7 (10%) non-cardiogenic deaths. The occurrence rate of HAVB
      but not severe TR or restrictive ASD was higher in 30 deceased patients than in
      43 survived patients [7 (23%) vs. 1 (2.3%), p = 0.0038]. The overall mortality
      rate was higher in patients with HAVB than in those without it (p = 0.0002). Of 7
      deceased patients with HAVB, 6 HAVB occurred within 10 days post-surgery, and 3
      HAVB led to the early death. The mortality rate of patients with prolonged PR (>=
      0.15 s) but not wide QRS (> 0.08 s) or prolonged QTc (> 0.43 s) at birth was
      higher than each without it (p = 0.0106). Multivariate analysis indicated that
      prolonged PR but no other variables was independently associated with the
      mortality (hazard ratio: 2.948, p = 0.0104). Prolonged PR at birth in HLHS
      infants predicts the development of fatal HAVB.

PMID- 29350248
TI  - Natural variation and genetic make-up of leaf blade area in spring barley.
AB  - KEY MESSAGE: GWAS analysis for leaf blade area (LA) revealed intriguing genomic
      regions associated with putatively novel QTL and known plant stature-related
      phytohormone and sugar-related genes. Despite long-standing studies in the morpho
      physiological characters of leaf blade area (LA) in cereal crops, advanced
      genetic studies to explore its natural variation are lacking. The importance of
      modifying LA in improving cereal grain yield and the genes controlling leaf
      traits have been well studied in rice but not in temperate cereals. To better
      understand the natural genetic variation of LA at four developmental stages, main
      culm LA was measured from 215 worldwide spring barleys including 92 photoperiod
      sensitive accessions [PHOTOPERIOD RESPONSE LOCUS 1 (Ppd-H1)] and 123 accessions
      with reduced photoperiod sensitivity (ppd-H1) locus under controlled greenhouse
      conditions (long-day; 16/8 h; ~ 20/~ 16  degrees C day/night). The LA of Ppd-H1
      carrying accessions was always smaller than in ppd-H1-carrying accessions. We
      found that nine SNPs from the Ppd-H1 gene were present in the collection of which
      marker 9 (M9; G/T in the CCT-domain) showed the most significant and consistent
      effect on LA at all studied developmental stages. Genome-wide association scans
      (GWAS) showed that the accessions carrying the ppd-H1 allele T/M9 (late heading)
      possessed more genetic variation in LA than the Ppd-H1 group carrying G/M9 (early
      heading). Several QTL with major effects on LA variation were found close to
      plant stature-related heading time, phytohormone- and sugar-related genes. The
      results provide evidence that natural variation of LA is an important source for
      improving grain yield, adaptation and canopy architecture of temperate cereals.

PMID- 29350249
TI  - Efficacy of phloroglucinol for treatment of abdominal pain: a systematic review
      of literature and meta-analysis of randomised controlled trials versus placebo.
AB  - AIM: Phloroglucinol is a musculotropic anti-spasmodic drug. It is frequently
      prescribed in many European countries with a considerable cost for health
      services. The purpose of this study was to review the existing randomised
      controlled trials (RCT) comparing the efficacy of phloroglucinol treating
      abdominal pain versus placebo. METHODS: A literature search was carried out up to
      May 2017 to select RCT comparing the effect of phloroglucinol versus placebo with
      intensity of abdominal pain as an endpoint. Studies concerning obstetric or
      gynaecologic-related pain were not included. RESULTS: Three RCT were included and
      then analysed for risk of bias and meta-analysed. Only one RCT found that
      phloroglucinol was superior to placebo, although with a high risk of bias. The
      meta-analysis found a risk ratio of 1.10 (95% CI 0.95, 1.27) with no statistical
      significance. DISCUSSION: There is insufficient data to justify the wide-spread
      prescription of phloroglucinol for alleviating abdominal pain.

PMID- 29350250
TI  - [Abdominal injuries in polytraumatized adults : Systematic review].
AB  - Abdominal injuries are potentially life-threatening and occur in 20-25% of all
      polytraumatized patients. Blunt trauma is the main mechanism. The liver and
      spleen are most commonly injured and much less often the intestines. The clinical
      evaluation proves equivocal in many cases; therefore, the gold standard is
      computed tomography (CT), which has been increasingly used even in
      hemodynamically weakly stable or sometimes even unstable patients because it
      promptly provides precise diagnostic findings, which present the basis for
      successful therapy. Hemodynamically unstable patients always need an exploratory
      laparotomy (EL). An EL should also be carried out with a positive focused
      assessment with sonography for trauma (FAST) or CT for severe parenchymal
      lesions, hollow organ lesions, intraperitoneal bladder lesions, peritonitis and
      organ evisceration, impalement injuries and lesions of the abdominal fascia.
      Hemodynamically stable patients without signs of peritonitis and a lack of such
      findings can often be treated conservatively irrespective of the extent of an
      injury. Angiography (and if needed embolization) can additionally be
      diagnostically and therapeutically utilized.

PMID- 29350251
TI  - Pyramidal cell-selective GluN1 knockout causes impairments in salience
      attribution and related EEG activity.
AB  - Schizophrenia is a disabling psychiatric disease characterized by symptoms
      including hallucinations, delusions, social withdrawal, loss of pleasure, and
      inappropriate affect. Although schizophrenia is marked by dysfunction in
      dopaminergic and glutamatergic signaling, it is not presently clear how these
      dysfunctions give rise to symptoms. The aberrant salience hypothesis of
      schizophrenia argues that abnormal attribution of motivational salience to
      stimuli is one of the main contributors to both positive and negative symptoms of
      schizophrenia. The proposed mechanisms for this hypothesis are overactive
      striatal dopaminergic and hypoactive glutamatergic signaling. The current study
      assessed salience attribution in mice (n = 72) using an oddball paradigm in which
      an infrequent stimulus either co-occurred with shock (conditioned group) or was
      presented alone (non-conditioned group). Behavioral response (freezing) and
      electroencephalogram (whole brain and amygdala) were used to assess salience
      attribution. Mice with pyramidal cell-selective knockout of ionotropic glutamate
      receptors (GluN1) were used to reproduce a prominent physiological change
      involved in schizophrenia. Non-conditioned knockout mice froze significantly more
      in response to the unpaired stimulus than non-conditioned wild-type mice,
      suggesting that this irrelevant cue acquired motivational salience for the
      knockouts. In accordance with this finding, low-frequency event-related spectral
      perturbation was significantly increased in non-conditioned knockout mice
      relative to both conditioned knockout and non-conditioned wild-type mice. These
      results suggest that pyramidal cell-selective GluN1 knockout leads to
      inappropriate attribution of salience for irrelevant stimuli as characterized by
      abnormalities in both behavior and brain circuitry functions.

PMID- 29350252
TI  - Risk factors of patients with pocket infection.

PMID- 29350253
TI  - Direct transfer of STEMI patients to cardiac catheterization laboratory :
      Prognostic relevance for in-hospital mortality.
AB  - BACKGROUND: Although the incidence of acute myocardial infarction and in-hospital
      mortality after ST-elevation myocardial infarction (STEMI) has declined
      substantially in countries that have established primary percutaneous coronary
      interventions (pPCI) over the past two decades, coronary artery disease remains a
      major cause of morbidity and mortality worldwide. We aimed to examine whether the
      direct transfer of STEMI patients to the cardiac catheterization laboratory (CCL)
      had a prognostic effect on in-hospital mortality in patients who underwent pPCI
      after STEMI. METHODS: The in-house mortality of STEMI patients who underwent pPCI
      was assessed at the Department of Cardiology, Harzklinik Goslar, Germany, between
      April 2013 and June 2017. RESULTS: We enrolled 312 STEMI patients, with a mean
      age of 67.1 +/- 13.4 years, of whom 211 (71%) were male. The all-cause in
      hospital mortality was 10% (n = 31 patients). A total of 298 (95%) patients were
      directly transferred to the CCL. while 14 patients (5%) with STEMI were not
      directly transferred to the CCL (tCCL) but were taken to the emergency department
      (tED). In the tCCL group, 18 patients (6%) died during the hospital stay,
      compared with 11 patients (79%) in the tED STEMI group; thus, the in-hospital
      mortality rate was significantly higher (p < 0.0001) in the tED group.
      CONCLUSION: Our monocentric cohort highlights and confirms the clinical
      importance of the direct transfer of patients with STEMI to the CCL. This
      approach is associated with a significant decrease in in-hospital mortality as
      compared with the tED approach.

PMID- 29350254
TI  - Sacubitril/valsartan for heart failure with reduced left ventricular ejection
      fraction : A retrospective cohort study.
AB  - BACKGROUND: The combination drug sacubitril/valsartan was reported to be superior
      to enalapril in reducing all-cause death, cardiovascular mortality, and heart
      failure (HF) hospitalizations in patients with cardiac insufficiency and reduced
      left ventricular ejection fraction (HFREF) with NYHA class II-IV. METHODS: Our
      retrospective cohort study aimed to assess the effects of sacubitril/valsartan in
      addition to a beta-blocker and mineral receptor antagonist (MRA) in a group of
      HFREF patients with NYHA class II-III HF vs. conventional therapy (ACE inhibitor
      or angiotensin II receptor blocker added to a beta-blocker plus an MRA)
      administered to a control group of HFREF patients with comparable clinical
      features. In both groups, treatment was supplemented by a loop diuretic, usually
      furosemide, at variable doses. The primary outcomes were all-cause death and HF
      hospitalizations. Safety outcomes were symptomatic hypotension, angioedema,
      hyperkalemia, and worsening renal function. RESULTS: Mortality at 6 months was
      6.8% in patients taking sacubitril/valsartan vs. 34% in those on conventional
      therapy (odds ratio [OR] = 0.14; 95% CI: 0.04-0.49). Moreover, there was a 4.5%
      rate of HF hospitalizations in the sacubitril/valsartan group vs. 59% in the
      control group (OR = 0.03; 95% CI: 0.01-0.14). Safety outcomes were comparable in
      the two groups, although hypotension (systolic blood pressure < 100 mm Hg) was
      found in 15.9% of patients in the sacubitril/valsartan group vs. 5.7% in the
      control group (OR = 3.14; 95% CI: 0.94-10.55). CONCLUSION: Sacubitril/valsartan
      offered strong protection against all-cause death and HF hospitalizations at 6
      months without any significant side effects. To validate this efficacious
      molecule, further postmarketing observational studies, focusing mainly on
      hypotension and angioedema are warranted.

PMID- 29350255
TI  - Nuclear magnetic resonance and high-performance liquid chromatography techniques
      for the characterization of bioactive compounds from Humulus lupulus L. (hop).
AB  - Humulus lupulus L. (hop) represents one of the most cultivated crops, it being a
      key ingredient in the brewing process. Many health-related properties have been
      described for hop extracts, making this plant gain more interest in the field of
      pharmaceutical and nutraceutical research. Among the analytical tools available
      for the phytochemical characterization of plant extracts, quantitative nuclear
      magnetic resonance (qNMR) represents a new and powerful technique. In this ambit,
      the present study was aimed at the development of a new, simple, and efficient
      qNMR method for the metabolite fingerprinting of bioactive compounds in hop
      cones, taking advantage of the novel ERETIC 2 tool. To the best of our knowledge,
      this is the first attempt to apply this method to complex matrices of natural
      origin, such as hop extracts. The qNMR method set up in this study was applied to
      the quantification of both prenylflavonoids and bitter acids in eight hop
      cultivars. The performance of this analytical method was compared with that of
      HPLC-UV/DAD, which represents the most frequently used technique in the field of
      natural product analysis. The quantitative data obtained for hop samples by means
      of the two aforementioned techniques highlighted that the amount of bioactive
      compounds was slightly higher when qNMR was applied, although the order of
      magnitude of the values was the same. The accuracy of qNMR was comparable to that
      of the chromatographic method, thus proving to be a reliable tool for the
      analysis of these secondary metabolites in hop extracts. Graphical abstract
      Graphical abstract related to the extraction and analytical methods applied in
      this work for the analysis of bioactive compounds in Humulus lupulus L. (hop)
      cones.

PMID- 29350256
TI  - Analysis of phenolic compounds in different parts of pomegranate (Punica
      granatum) fruit by HPLC-PDA-ESI/MS and evaluation of their antioxidant activity:
      application to different Italian varieties.
AB  - The analysis of pomegranate phenolic compounds belonging to different classes in
      different fruit parts was performed by high-performance liquid chromatography
      coupled with photodiode array and mass spectrometry detection. Two different
      separation methods were optimized for the analysis of anthocyanins and
      hydrolyzable tannins along with phenolic acids and flavonoids. Two C18 columns,
      core-shell and fully porous particle stationary phases, were used. The parameters
      for separation of phenolic compounds were optimized considering chromatographic
      resolution and analysis time. Thirty-five phenolic compounds were found, and 28
      of them were tentatively identified as belonging to four different phenolic
      compound classes; namely, anthocyanins, phenolic acids, hydrolyzable tannins, and
      flavonoids. Quantitative analysis was performed with a mixture of nine phenolic
      compounds belonging to phenolic compound classes representative of pomegranate.
      The method was then fully validated in terms of retention time precision,
      expressed as the relative standard deviation, limit of detection, limit of
      quantification, and linearity range. Phenolic compounds were analyzed directly in
      pomegranate juice, and after solvent extraction with a mixture of water and
      methanol with a small percentage of acid in peel and pulp samples. The accuracy
      of the extraction method was also assessed, and satisfactory values were
      obtained. Finally, the method was used to study identified analytes in
      pomegranate juice, peel, and pulp of six different Italian varieties and one
      international variety. Differences in phenolic compound profiles among the
      different pomegranate parts were observed. Pomegranate peel samples showed a high
      concentration of phenolic compounds, ellagitannins being the most abundant ones,
      with respect to pulp and juice samples for each variety. With the same samples,
      total phenols and antioxidant activity were evaluated through colorimetric
      assays, and the results were correlated among them.

PMID- 29350257
TI  - A new approach for the extraction of tetracyclines from soil matrices:
      application of the microwave-extraction technique.
AB  - The widespread use of tetracyclines (TCs) in animal husbandry is associated with
      their constant penetration into the environment and the threat they might pose to
      living organisms. While the literature data on the analysis of these substances
      in such matrices as food, tissues, or wastewater are quite extensive, there are
      still only a few methods presented for the determination of these compounds in
      soil samples. Moreover, among the literature methods for the extraction of TCs
      from soil samples, microwave-assisted solvent extraction (MAE) was used only once
      and in combination with liquid chromatography with spectrophotometric detection
      (LC-UV). However, according to the EU Commission Decision 2002/657/EC, the use of
      LC-UV for the determination of compounds, including pharmaceuticals, in
      environmental samples is not sufficient. Therefore, the development and
      application of a sensitive and selective method using the MAE-SPE-LC-MS/MS(MRM)
      technique for the isolation and identification of a mixture of oxytetracycline
      (OTC), tetracycline (TC), and chlortetracycline (CTC) in soils is presented in
      our study. The credibility of this method has been confirmed with good parameters
      of validation. The optimal extraction conditions of three TCs using MAE
      techniques were to conduct double extraction for 10 min each, at 60  degrees C,
      using a mixture of ACN:McIlvaine buffer:0.1 M EDTA (2:1:1, v/v/v) and an
      additional cleaning of the extracts by SPE. The effectiveness of the extraction
      of these compounds was assessed based on two different ways (absolute recovery
      from 46 to 65.1% and relative recovery from 101.1 to 109.5%). Finally, the
      validated MAE-SPE-LC-MS/MS(MRM) method was used for the analysis of six samples
      from agricultural areas of northern Poland. OTC and TC, at concentrations of 11.7
      and 14.5 MUg kg-1 were determined in two different samples. An assessment of risk
      quotients was also performed. The presented method was proven to be a useful tool
      in the analysis of residues of selected TCs in the soil ecosystem. Obtained data
      on the presence of these drugs in Polish soils is the first report for this
      country.

PMID- 29350258
TI  - Antitumor effects of radionuclide treatment using alpha-emitting meta-211At
      astato-benzylguanidine in a PC12 pheochromocytoma model.
AB  - PURPOSE: Therapeutic options for patients with malignant pheochromocytoma are
      currently limited, and therefore new treatment approaches are being sought.
      Targeted radionuclide therapy provides tumor-specific systemic treatments. The
      beta-emitting radiopharmaceutical meta-131I-iodo-benzylguanidine (131I-MIBG)
      provides limited survival benefits and has adverse effects. A new generation of
      radionuclides for therapy using alpha-particles including meta-211At-astato
      benzylguanidine (211At-MABG) are expected to have strong therapeutic effects with
      minimal side effects. However, this possibility has not been evaluated in an
      animal model of pheochromocytoma. We aimed to evaluate the therapeutic effects of
      the alpha-emitter 211At-MABG in a pheochromocytoma model. METHODS: We evaluated
      tumor volume-reducing effects of 211At-MABG using rat pheochromocytoma cell line
      PC12 tumor-bearing mice. PC12 tumor-bearing mice received intravenous injections
      of 211At-MABG (0.28, 0.56, 1.11, 1.85, 3.70 and 5.55 MBq; five mice per group).
      Tumor volumes were evaluated for 8 weeks after 211At-MABG administration. The
      control group of ten mice received phosphate-buffered saline. RESULTS: The 211At
      MABG-treated mice showed significantly lower relative tumor growth during the
      first 38 days than the control mice. The relative tumor volumes on day 21 were
      509.2% +/- 169.1% in the control mice and 9.6% +/- 5.5% in the mice receiving
      0.56 MBq (p < 0.01). In addition, the mice treated with 0.28, 0.56 and 1.11 MBq
      of 211At-MABG showed only a temporary weight reduction, with recovery in weight
      by day 10. CONCLUSION: 211At-MABG exhibited a strong tumor volume-reducing effect
      in a mouse model of pheochromocytoma without weight reduction. Therefore, 211At
      MABG might be an effective therapeutic agent for the treatment of malignant
      pheochromocytoma.

PMID- 29350259
TI  - Diminished expression of beta2-GPI is associated with a reduced ability to
      mitigate complement activation in anti-GPIIb/IIIa-mediated immune
      thrombocytopenia.
AB  - Anti-GPIIb/IIIa-mediated complement activation has been reported to be important
      in the pathogenesis of immune thrombocytopenia (ITP). However, the role of the
      complement system and the involved regulatory mechanism remain equivocal. Beta2
      glycoprotein I (beta2-GPI), known as the main target for antiphospholipid
      autoantibodies, has been demonstrated as a complement regulator. Here, we
      investigated the complement-regulatory role of beta2-GPI in anti-GPIIb/IIIa
      mediated ITP. Plasma complement activation and enhanced complement activation
      capacity (CAC) were found in ITP patients with anti-GPIIb/IIIa antibodies in vivo
      and in vitro. Diminished plasma levels of beta2-GPI were shown in patients of
      this group, which was inversely correlated with C5b-9 deposition. C5b-9
      generation was inhibited by approximate physiological concentrations of beta2
      GPI, in a dose-dependent manner. Inhibition of C3a generation by beta2-GPI and
      the existence of beta2-GPI/C3 complexes in plasma indicated a regulation on the
      level of the C3 convertase. Furthermore, beta2-GPI down-regulated the
      phosphorylation levels of c-Jun N-terminal kinase (JNK) and cleavage of BH3
      interacting domain death agonist (Bid) and ultimately harbored platelet lysis.
      Our findings may provide a novel link between diminished plasma levels of beta2
      GPI and enhanced complement activation, indicating beta2-GPI as a potential
      diagnostic biomarker and therapeutic target in the treatment of anti-GPIIb/IIIa
      mediated ITP.

PMID- 29350260
TI  - Modulation rate transfer functions from four species of stranded odontocete
      (Stenella longirostris, Feresa attenuata, Globicephala melas, and Mesoplodon
      densirostris).
AB  - Odontocete marine mammals explore the environment by rapidly producing
      echolocation signals and receiving the corresponding echoes, which likewise
      return at very rapid rates. Thus, it is important that the auditory system has a
      high temporal resolution to effectively process and extract relevant information
      from click echoes. This study used auditory evoked potential methods to
      investigate auditory temporal resolution of individuals from four different
      odontocete species, including a spinner dolphin (Stenella longirostris), pygmy
      killer whale (Feresa attenuata), long-finned pilot whale (Globicephala melas),
      and Blainville's beaked whale (Mesoplodon densirostris). Each individual had
      previously stranded and was undergoing rehabilitation. Auditory Brainstem
      Responses (ABRs) were elicited via acoustic stimuli consisting of a train of
      broadband tone pulses presented at rates between 300 and 2000 Hz. Similar to
      other studied species, modulation rate transfer functions (MRTFs) of the studied
      individuals followed the shape of a low-pass filter, with the ability to process
      acoustic stimuli at presentation rates up to and exceeding 1250 Hz. Auditory
      integration times estimated from the bandwidths of the MRTFs ranged between 250
      and 333 us. The results support the hypothesis that high temporal resolution is
      conserved throughout the diverse range of odontocete species.

PMID- 29350261
TI  - Publication rates of the abstracts presented at the annual meeting of
      International Society for Pediatric Neurosurgery.
AB  - INTRODUCTION: Publication of a study is the end point of the process to
      contribute to the literature and confirm the scientific value of the study.
      Publication rates of the abstracts presented at the annual meetings of
      neurosurgery have been studied, previously. However, publication rates of the
      abstracts presented at the annual meetings of pediatric neurosurgery have not
      been reported, yet. We evaluated abstracts presented at the 38th annual meeting
      of the International Society for Pediatric Neurosurgery (ISPN) held in South
      Korea, 2010. METHODS: We conducted this cross-sectional study by reviewing the
      abstracts presented at the annual meeting of the ISPN, 2010. Titles and authors
      of the abstracts were surveyed using Google Scholar and PubMed/MEDLINE. Time to
      publication, origin of the study, journal name in which the study has been
      accepted and published, and type of study has been analyzed for each abstract.
      RESULTS: The abstract booklet included 235 abstracts, consisted of 128 oral
      presentations (54%) and 107 electronic posters (46%). Fifty-nine (46%) of the
      oral presentations were published in a peer-reviewed journal. Laboratory studies
      were more likely to be published when compared to the clinical studies (72 vs.
      39%). Thirty-two (30%) of the electronic posters were published in peer-reviewed
      journals. Most of the published abstracts were from Asia and Europe. Most of the
      abstracts were published in Child's Nervous System and Journal of Neurosurgery:
      Pediatrics. CONCLUSION: Publication rates of the abstracts presented at annual
      meeting of the ISPN were comparable to the other similar congresses. Oral
      presentations were more likely to be published. High publication rates of the
      abstracts presented at the annual meeting of the ISPN suggested that the meeting
      had a high scientific value.

PMID- 29350262
TI  - Vagal nerve stimulation for medically refractory epilepsy in Angelman syndrome: a
      series of three cases.
AB  - BACKGROUND: We describe three children with Angelman syndrome and medically
      refractory epilepsy. METHODS: Case series of three pediatric patients with
      Angelman syndrome and medically refractory epilepsy. All three patients failed
      medical treatment and were recommended for vagal nerve stimulator (VNS)
      implantation. RESULTS: Following VNS implantation, all three patients experienced
      reduction in seizure frequency greater than that afforded by medication alone.
      CONCLUSION: We present vagal nerve stimulator implantation as a viable treatment
      option for medically refractory epilepsy associated with Angelman syndrome.

PMID- 29350263
TI  - Histological findings after argon plasma coagulation: an ex-vivo study revealing
      a possible role in superficial ablative treatment of the skin.
AB  - Argon plasma coagulation (APC) is an electrosurgical technique which can be used
      to ablate skin lesions with limited invasion depth into dermal tissue. Hence, APC
      might be well suited for the removal of epithelial tumours. However, there are no
      data on the effects of APC on human skin tissue. Thus, the aim of this study was
      to determine the extent of epidermal and dermal damage after APC of human skin.
      We performed APC ex-vivo on 91 freshly resected human skin samples, which were
      obtained after reconstructive surgical closures in actinically damaged areas.
      Tissue effects were evaluated histologically and compared across different power
      settings. Using 15, 30, and 45 W, median (interquartile range; IQR) coagulation
      depths were 110.0 um (91.7-130.0), 113.3 um (85.8-135.0), and 130.0 um (100.0
      153.3.0), respectively. Median (IQR) thickness of necrosis zone was 30.0 um (23.3
      40.0) at 15 W, 26.7 um (20.0-41.6) at 30 W, and 43.3 um (30.8-57.5) at 45 W. The
      Kruskal-Wallis test showed significant differences between 15 and 30 W versus 45
      W for coagulation depth (P = 0.0414), necrosis zone (P = 0.0017), and necrosis
      according to overlaying epidermal thickness (P = 0.0467). In summary, APC is a
      simple and controllable electrosurgical technique to remove epidermal tissue with
      limited penetration to the dermis. Thus, APC is particularly suited for the
      ablation of epithelial skin lesions and, therefore, may serve as possible
      treatment approach for intraepithelial neoplasms such as actinic keratosis.

PMID- 29350265
TI  - Effects of exercise-based interventions in severe mental illness: a feasibility
      study.

PMID- 29350264
TI  - Linking muscle metabolism and functional variation to field swimming performance
      in bluegill sunfish (Lepomis macrochirus).
AB  - Skeletal muscle has diverse mechanical roles during locomotion. In swimming fish,
      power-producing muscles work in concert with the accessory muscles of the fins
      which augment and control power transfer to the water. Although fin muscles
      represent a significant proportion of the locomotor muscle mass, their
      physiological properties are poorly characterized. To examine the relationship
      between muscle metabolism and the differing mechanical demands placed on distinct
      muscle groups, we quantified the aerobic and glycolytic capacities of the
      myotomal, pectoral and caudal muscles of bluegill sunfish. These were indicated
      by the activities of citrate synthase and lactate dehydrogenase, rate-limiting
      enzymes for aerobic respiration and glycolysis, respectively. The well
      established roles of slow and fast myotomal muscle types in sustained and
      transient propulsive movements allows their use as benchmarks to which other
      muscles can be compared to assess their function. Slow myotomal muscle had the
      highest CS activity, consistent with meeting the high metabolic and mechanical
      power demands of body-caudal fin (BCF) swimming at the upper end of the
      aerobically supported speed range. The largest pectoral adductors and abductors
      had CS activities lower than the slow myotomal muscle, in line with their role
      supplying thrust for low-speed, low-power swimming. The metabolic capacities of
      the caudal muscles were surprisingly low and inconsistent with their activity
      during steady-state BCF swimming at high speeds. This may reflect adaptation to
      the observed swimming behavior in the field, which typically involved short bouts
      of BCF-propulsive cycles rather than sustained propulsive activity.

PMID- 29350266
TI  - Normative measurements of inferior oblique muscle thickness in Japanese by
      magnetic resonance imaging using a new technique.
AB  - PURPOSE: To measure the thickness of the inferior oblique muscle (IOM) among
      Japanese by magnetic resonance imaging (MRI) using a new technique. METHODS: This
      retrospective observational study included 78 patients (36 males and 42 females)
      who underwent MRI for detection of a unilateral orbital lesion or examining
      causes of unilateral retrobulbar pain. The thickness of the IOM was measured on
      the side without the orbital lesion or symptom. On the quasi-sagittal plane
      through the optic nerve, the major and minor axes of the cross-section of the IOM
      were measured. On the coronal plane, the maximum thickness perpendicular to the
      course of the IOM was measured. All measurements were performed using the digital
      caliper tool of the viewing software. RESULTS: The major and minor axes on the
      quasi-sagittal plane and the maximum IOM thickness on the coronal plane were 8.00
      +/- 1.83 mm, 2.98 +/- 0.55 mm, 3.04 +/- 0.55 mm respectively. There were no
      significant differences in IOM thickness measurements between sexes and sides (P
      > 0.050, Student's t-test). No significant correlation with the major axis (r =
      0.064, P = 0.576), minor axis (r = -0.065, P = 0.573) or the maximum thickness on
      the coronal plane (r = -0.099, P = 0.387) was found in relation to age (Pearson's
      correlation coefficient). CONCLUSIONS: The normative IOM thickness in Japanese
      was presented on MRI, which were similar among all ages irrespective of sex and
      side. The new technique we used is easily applicable, and the results may serve
      as a guide to detect IOM involvement in inflammatory and neoplastic conditions of
      the orbit.

PMID- 29350268
TI  - The epitope-mediated MMP activation assay: detection and quantification of the
      activation of Mmp2 in vivo in the zebrafish embryo.
AB  - Matrix remodeling is a consequence of tightly regulated matrix metalloproteinase
      (MMP) activity. MMPs are synthesized as inactive precursors with auto-inhibitory
      N-terminal propeptides, the proteolytic removal of which exposes the catalytic
      zinc ion, rendering the protease active. The regulation of MMP activation has
      been investigated primarily in tissue culture and biochemical assays that lack
      important biological context. Here we present the epitope-mediated MMP activation
      (EMMA) assay and use it to observe the activation of Mmp2 (gelatinase A) by
      endogenous mechanisms in the intact zebrafish embryo. The hemagglutinin (HA) and
      GFP-tagged reporter construct becomes activated on the surface of specific cells
      and this activation is abolished by broad-spectrum inhibition of
      metalloproteinase activity, consistent with existing models of gelatinase A
      activation. The mechanism(s) acting on the construct are spatially restricted,
      metalloproteinase-dependent and replacing the HA tag with mCherry abolishes
      activation, showing that the mechanism(s) are sensitive to the structure of the N
      terminal domain. The construct is activated strongly in maturing myotome
      boundaries, but also intracellularly within myofibrils, consistent with reports
      implicating this protease in muscle development and function. In addition to
      general-purpose tools for the production of "EMMAed" MMPs and other proteins, we
      have established a transgenic line of zebrafish expressing EMMAedMmp2 under
      control of an inducible promoter to facilitate further investigation into the
      regulation of this ubiquitous ECM-remodeling protease in vivo.

PMID- 29350270
TI  - Genetic data for 26 autosomal STR markers from Brazilian population.
AB  - The allelic frequency distributions and statistical forensic parameters of 26
      mini short tandem repeat (mini-STR) loci in a sample of 1575 unrelated
      individuals from five different Brazilian regions were obtained. All the analyzed
      loci showed great diversity and were highly informative. The results were
      compared with those of the US Caucasian, African American, and Hispanic
      population studies. This study aimed to contribute to forensic analysis for human
      identification and inference of the evidential value in familial bond tests.

PMID- 29350269
TI  - Exome analysis in 34 sudden unexplained death (SUD) victims mainly identified
      variants in channelopathy-associated genes.
AB  - Sudden cardiac death (SCD) is one of the major causes of mortality worldwide,
      mostly involving coronary artery disease in the elderly. In contrary, sudden
      death events in young victims often represent the first manifestation of
      undetected genetic cardiac diseases, which remained without any symptoms during
      lifetime. Approximately 30% of these sudden death cases have no definite cardiac
      etiology after a comprehensive medicolegal investigation and are therefore termed
      as sudden unexplained death (SUD) cases. Advances in high-throughput sequencing
      approaches have provided an efficient diagnostic tool to identify likely
      pathogenic variants in cardiovascular disease-associated genes in otherwise
      autopsy-negative SUD cases. The aim of this study was to genetically investigate
      a cohort of 34 unexplained death cases by focusing on candidate genes associated
      with cardiomyopathies and channelopathies. Exome analysis identified potentially
      disease-causing sequence alterations in 29.4% of the 34 SUD cases. Six (17.6%)
      individuals had variants with likely functional effects in the channelopathy
      associated genes AKAP9, KCNE5, RYR2, and SEMA3A. Interestingly, four of these six
      SUD individuals were younger than 18 years of age. Since the total SUD cohort of
      this study included five children and adolescents, post-mortem molecular autopsy
      screening indicates a high diagnostic yield within this age group. Molecular
      genetic testing represents a valuable approach to uncover the cause of death in
      some of the SUD victims; however, 70-80% of the cases still remain elusive,
      emphasizing the importance of additional research to better understand the
      pathological mechanisms leading to a sudden death event.

PMID- 29350267
TI  - Modern work-up and extended resection in perihilar cholangiocarcinoma: the AMC
      experience.
AB  - AIM: Perihilar cholangiocarcinoma (PHC) is a challenging disease and requires
      aggressive surgical treatment in order to achieve curation. The assessment and
      work-up of patients with presumed PHC is multidisciplinary, complex and requires
      extensive experience. The aim of this paper is to review current aspects of
      diagnosis, preoperative work-up and extended resection in patients with PHC from
      the perspective of our own institutional experience with this complex tumor.
      METHODS: We provided a review of applied modalities in the diagnosis and work-up
      of PHC according to current literature. All patients with presumed PHC in our
      center between 2000 and 2016 were identified and described. The types of
      resection, surgical techniques and outcomes were analyzed. RESULTS AND
      CONCLUSION: Upcoming diagnostic modalities such as Spyglass and combinations of
      serum biomarkers and molecular markers have potential to decrease the rate of
      misdiagnosis of benign, inflammatory disease. Assessment of liver function with
      hepatobiliary scintigraphy provides better information on the future remnant
      liver (FRL) than volume alone. The selective use of staging laparoscopy is
      advisable to avoid futile laparotomies. In patients requiring extended resection,
      selective preoperative biliary drainage is mandatory in cholangitis and when FRL
      is small (< 50%). Preoperative portal vein embolization (PVE) is used when FRL
      volume is less than 40% and optionally includes the left portal vein branches to
      segment 4. Associating liver partition and portal vein ligation for staged
      hepatectomy (ALPPS) as alternative to PVE is not recommended in PHC. N2 positive
      lymph nodes preclude long-term survival. The benefit of unconditional en bloc
      resection of the portal vein bifurcation is uncertain. Along these lines, an
      aggressive surgical approach encompassing extended liver resection including
      segment 1, regional lymphadenectomy and conditional portal venous resection
      translates into favorable long-term survival.

PMID- 29350271
TI  - Development of unstable hips after treatment with the Tubingen splint: mid-term
      follow-up of 83 hip joints.
AB  - INTRODUCTION: Early diagnosis and treatment of hip dysplasia are widely accepted
      as major factors for beneficial outcome. However, modalities for reduction and
      retention as well as for imaging are currently under clinical investigation.
      Local and general risk factors, e.g., breech presentation and the family's desire
      to avoid in-hospital treatment are major concerns in the decision-making process
      and consultation. For treatment of unstable hips in newborns the treatment with
      the Tubingen splint has proven good results in recent studies. However, mid- and
      long-term outcome studies are missing. We report on clinical results and X-ray
      parameter of initially unstable hips after treatment with the Tubingen splint at
      two time points: 12-24 and 24-48 months of age. MATERIALS AND METHODS: Included
      were newborns with 83 unstable hips (type D, III, IV according to Graf) which
      were successfully treated with the Tubingen splint-used as reduction splint 24 h
      per day/7 days per week-until type I hips were documented by ultrasound
      examination. Measurments are based on routine pelvic X-ray control at the age of
      12-24 and 24-48 months. The acetabular angle was determined and according to the
      Tonnis-Classification evaluated into: normal findings (< 1 s), slightly
      dysplastic findings (1-2 s) and severely dysplastic findings (> 2 s). Children
      with secondary hip dysplasia were not included in this series. RESULTS: In 2nd
      year of life, 45 hips (54.2%; initial hip type D: 47.4%, III: 63.2%, IV: 42.9%)
      of the formerly unstable hips show normal X-ray findings. Although final
      ultrasound showed normal findings, at this time point 28 hips (33.7%; initial hip
      type D: 34.2%, III: 31.6%, IV: 42.9%) were slightly dysplastic and 10 (12.0%%;
      initial hip type D: 18.4%, III: 5.3%, IV: 14.3%) still severely dysplastic. At
      the age of 24-48 months, the percentage of radiologic normal hips had increased
      to 61 hips (73.5%; initial hip type D: 68.4%, III: 81.6%, IV: 57.1%), the number
      of slightly (19 hips) and severely dysplastic (3 hips) hips had decreased 22.9%
      (initial hip type D: 28.9%, III: 15.8%, IV: 28.6%) respectively 3.6% (initial hip
      type D: 2.6%, III: 2.6%, IV: 14.3%). At this time no operative intervention was
      neccessary. CONCLUSIONS: Our mid-term data show on the one hand a good
      development of unstable hips after successful treatment with the Tubingen splint.
      On the other hand despite successful therapy and normal ultrasound findings at
      the end of treatment further imaging by X-ray are mandatory to close follow-up
      and to detect those which might need surgical correction of residual dysplasia.

PMID- 29350272
TI  - Endoscopic endonasal approach for trigeminal schwannomas: our experience of 39
      patients in 10 years.
AB  - BACKGROUND: The anatomical locations involved in trigeminal schwannomas (TSs) are
      quite complex. The endoscopic endonasal approach provides a minimal damage access
      corridor to both anterior and middle skull base for surgery. Given the nerve
      function recovery and postoperative neurological deterioration varied in
      different reports, the author demonstrates his surgery tips and the functional
      outcomes under endoscopic surgery in one single institution. METHODS: A
      retrospective review of patients with TSs was undertaken to assess the outcome of
      endoscopic surgery from 2006 to 2016. Clinical features, imaging findings,
      preoperative/postoperative neurological deficits, surgical approaches and
      followed up data were collected. RESULTS: Thirty-nine patients with TSs were
      included in this study. Surgical approaches include endoscopic medial
      maxillectomy approach (n = 8), endoscopic endonasal-assisted sublabial
      transmaxillary approach (n = 27) and endoscopic endonasal-assisted sublabial
      transmaxillary combined with septectomy (n = 4). Gross total resection and sub
      total resection were achieved in 27 and 10 patients, respectively. The most
      common chief complaint was facial numbness, accounting for 41%, with a resolved
      rate of 62.5% after treatment. Fifteen patients developed new neurologic
      symptoms, including facial numbness/pain (n = 9 and 2, respectively), dry eye (n
      = 3) and mastication weakness (n = 1). Eight of these patients had partial
      improvement except for patients with dry eye. CONCLUSION: Endoscopic endonasal
      approach represents a safe and effective surgical procedure for TSs in
      pterygopalatine fossa, infratemporal fossa and even Meckel cave. Tumor resection
      can be achieved by endoscope with few neurologic deficits and complications.

PMID- 29350273
TI  - In response to "Calculation of indirect costs of associated with postoperative
      caregiver absences after pediatric tonsil surgery".

PMID- 29350275
TI  - Value of transperineal ultrasound on the observation of paravaginal support.
AB  - OBJECTIVE: To explore the feasibility of three-dimensional (3D) transperineal
      ultrasound on the observation of paravaginal support in nulliparous and
      postpartum women. METHODS: Volume datasets were acquired in 50 nulliparous and
      100 postpartum women using 3D transperineal ultrasound. Paravaginal supports were
      observed by studying the vaginal cross-sectional morphology. The extent of
      paravaginal support in specific level were evaluated by counting out at a 2 mm
      interval in tomographic ultrasound imaging mode in all subjects. The Mann-Whitney
      U test were applied to establish comparisons between the two groups. RESULTS:
      Three representative manifestations of vaginal cross-sectional morphology
      corresponding to different paravaginal support were presented from the dorsal
      side to the caudal side, both in nulliparous women and postpartum women. The
      extent of paravaginal support in middle vagina was 11 slices (range 9-12) in
      nulliparous women and 7 slices (range 4-10) in postpartum women (P < 0.05).
      CONCLUSION: This pilot study confirmed that it was feasible to indirectly study
      paravaginal support by observing the vaginal cross-sectional morphology using 3D
      transperineal ultrasound.

PMID- 29350274
TI  - T lymphocytes facilitate brain metastasis of breast cancer by inducing Guanylate
      Binding Protein 1 expression.
AB  - The discovery of genes and molecular pathways involved in the formation of brain
      metastasis would direct the development of therapeutic strategies to prevent this
      deadly complication of cancer. By comparing gene expression profiles of Estrogen
      Receptor negative (ER-) primary breast tumors between patients who developed
      metastasis to brain and to organs other than brain, we found that T lymphocytes
      promote the formation of brain metastases. To functionally test the ability of T
      cells to promote brain metastasis, we used an in vitro blood-brain barrier (BBB)
      model. By co-culturing T lymphocytes with breast cancer cells, we confirmed that
      T cells increase the ability of breast cancer cells to cross the BBB. Proteomics
      analysis of the tumor cells revealed Guanylate-Binding Protein 1 (GBP1) as a key
      T lymphocyte-induced protein that enables breast cancer cells to cross the BBB.
      The GBP1 gene appeared to be up-regulated in breast cancer of patients who
      developed brain metastasis. Silencing of GBP1 reduced the ability of breast
      cancer cells to cross the in vitro BBB model. In addition, the findings were
      confirmed in vivo in an immunocompetent syngeneic mouse model. Co-culturing of
      ErbB2 tumor cells with activated T cells induced a significant increase in Gbp1
      expression by the cancer cells. Intracardial inoculation of the co-cultured tumor
      cells resulted in preferential seeding to brain. Moreover, intracerebral
      outgrowth of the tumor cells was demonstrated. The findings point to a role of T
      cells in the formation of brain metastases in ER- breast cancers, and provide
      potential targets for intervention to prevent the development of cerebral
      metastases.

PMID- 29350276
TI  - Effect of swimming exercise on premenstrual syndrome.
AB  - OBJECTIVE: To study the effectiveness of performing swimming on the severity of
      symptoms of premenstrual syndrome (PMS). MATERIALS AND METHODS: A randomized
      controlled trial that was conducted on 70 women diagnosed with PMS divided
      randomly into two equal groups: Group I included women who engaged into exercise
      and group II controls. Daily Symptoms Report was filled at the start and at end
      of the study. RESULTS: At the posttreatment evaluation, there was a highly
      significant difference between the study and control groups regarding anxiety (0
      vs. 5), depression (3 vs. 12), tension (3 vs. 12), mood changes (0 vs. 7),
      feeling out of control (0 vs. 7), weak coordination (0 vs. 10), confusion (2 vs.
      9), headache (3 vs. 15), tiredness (4 vs. 12), pains (5 vs. 11), tenderness of
      the breast (2 vs. 8), and cramps (6 vs. 17) (P < 0.001), but no such difference
      was found regarding irritability, insomnia, crying, swelling, or food craving.
      Regarding the percentage of symptoms changes, there was a highly significant
      difference between the study and control groups regarding anxiety (- 33.3 vs. 0),
      depression (- 79.29 vs. 15.56), tension (- 81.18 vs. - 6.79), mood changes (-
      33.33 vs. 0), feeling out of control (- 91.67 vs. 0), weak coordination (- 100
      vs. - 9.55), sleeplessness (- 71.43 vs. 0), confusion (- 84.17 vs. - 9.55),
      headache (- 77.78 vs. - 6.94), fatigue (- 65.69 vs. 0), pains (- 65.83 vs. -
      8.93), breast tenderness (- 87.87 vs. 4.55), cramps (- 60.77 vs. 4.55), and
      swellings (- 55.05 vs. - 8.33), but no such difference was found regarding
      irritability, crying, or food craving. CONCLUSIONS: There is beneficial effect of
      swimming on most of the physical and psychological symptoms of PMS. CLINICAL
      TRIAL REGISTRY NO: NCT03264612.

PMID- 29350278
TI  - Lower body blood flow restriction training may induce remote muscle strength
      adaptations in an active unrestricted arm.
AB  - PURPOSE: We examined the concurrent characteristics of the remote development of
      strength and cross-sectional area (CSA) of upper body skeletal muscle in response
      to lower body resistance training performed with an applied blood flow
      restriction (BFR). METHODS: Males allocated to an experimental BFR group (EXP; n
      = 12) or a non-BFR control group (CON; n = 12) completed 7-weeks of resistance
      training comprising three sets of unilateral bicep curls [50% 1-repetition
      maximum (1-RM)], then four sets of bilateral knee extension and flexion exercises
      (30% 1-RM). EXP performed leg exercises with an applied BFR (60% limb occlusion
      pressure). 1-RM strength was measured using bilateral leg exercises and
      unilateral bicep curls in both trained and untrained arms. Muscle CSA was
      measured via peripheral quantitative computed tomography in the dominant leg and
      both arms. RESULTS: 1-RM in the trained arm increased more in EXP (2.5 +/- 0.4
      kg; mean +/- SEM) than the contralateral untrained arm (0.8 +/- 0.4 kg), and the
      trained arm of CON (0.6 +/- 0.3 kg, P < 0.05). The increase in knee extension 1
      RM was twofold that of CON (P < 0.01). Knee flexion 1-RM, leg CSA, and trained
      arm CSA increased similarly between groups (P > 0.05), while untrained arm CSA
      did not change (P > 0.05). CONCLUSION: Lower limb BFR training increased trained
      arm strength more than the contralateral untrained arm, and the trained arm of
      controls. However, there was no additional effect on muscle CSA. These findings
      support evidence for a BFR training-derived remote strength transfer that may be
      relevant to populations with localised movement disorders.

PMID- 29350279
TI  - Evaluation of the convergent validity of an estimated cardiorespiratory fitness
      algorithm.
AB  - PURPOSE: Examine the convergent validity of a cardiorespiratory fitness (CRF)
      algorithm when compared to treadmill-assessed CRF. METHODS: Data from the 1999
      2004 NHANES were used (N = 3259 adults 20-49 years). Cardiorespiratory fitness
      was estimated from an algorithm. Participants completed a submaximal treadmill
      based protocol. We (1) evaluated the pairwise association (and ICC) between
      estimated and measured cardiorespiratory fitness, (2) employed a paired samples t
      test to examine potential mean differences between estimated and measured
      cardiorespiratory fitness, (3) constructed a Bland-Altman plot and 95% limits of
      agreement (LoA) to explore systematic differences and random error between
      estimated and measured cardiorespiratory fitness, and (4) examined the
      association (via linear regression) of estimated and measured cardiorespiratory
      fitness with chronic disease prevalence and C-reactive protein (CRP). RESULTS:
      Mean estimated CRF (10.68 METs) was lower than the mean measured CRF of 11.37
      METs (p < 0.0001). The calculated pairwise correlation was of a moderate
      strength, r = 0.43 (p < 0.0001), with an ICC of 0.40 (p < 0.001). Calculated LoA
      indicated that estimated CRF may differ from measured CRF by 40% below to 48%
      above. Regression analyses yielded statistically significant inverse associations
      of estimated (unstandardized coefficient = - 0.026; p < 0.001) and measured
      (unstandardized coefficient = - 0.007; p = 0.002) CRF with chronic disease and
      estimated (unstandardized coefficient = - 0.08; p < 0.001) and measured
      (unstandardized coefficient = - 0.03; p < 0.001) CRF with CRP. CONCLUSION:
      Measured and estimated CRF were moderately correlated. However, estimated and
      measured CRF were statistically significant different from one another with
      noteworthy scatter around the average difference. As such, when feasible,
      objective measurements of CRF should be taken.

PMID- 29350280
TI  - Selective precipitation and characterization of lignin-carbohydrate complexes
      (LCCs) from Eucalyptus.
AB  - MAIN CONCLUSION: Six types of lignin-carbohydrate complex (LCC) fractions were
      isolated from Eucalyptus. The acidic dioxane treatment applied significantly
      improved the yield of LCCs. The extraction conditions had a limited impact on the
      LCC structures and linkages. Characterization of the lignin-carbohydrate complex
      (LCC) structures and linkages promises to offer insight on plant cell wall
      chemistry. In this case, Eucalyptus LCCs were extracted by aqueous dioxane, and
      then precipitated sequentially by 70% ethanol, 100% ethanol, and acidic water (pH
      = 2). The composition and structure of the six LCC fractions obtained by
      selective precipitation were investigated by sugar analysis, molecular weight
      determination, and 2D HSQC NMR. It was found that the acidic (0.05-M HCl) dioxane
      treatment significantly improved the yield of LCCs (66.4% based on Klason
      lignin), which was higher than the neutral aqueous dioxane extraction, and the
      extraction condition showed limited impact on the LCC structures and linkages. In
      the fractionation process, the low-molecular-weight LCCs containing a high
      content of carbohydrates (60.3-63.2%) were first precipitated by 70% ethanol from
      the extractable solution. The phenyl glycoside (PhGlc) bonds (13.0-17.0 per
      100Ar) and highly acetylated xylans were observed in the fractions recovered by
      the precipitation with 100% ethanol. On the other hand, such xylan-rich LCCs
      exhibited the highest frequency of beta-O-4 linkages. The benzyl ether (BE) bonds
      were only detected in the fractions obtained by acidic water precipitation.

PMID- 29350282
TI  - Neutrophil chemotaxis.
AB  - Neutrophils are the primary cells recruited to inflamed sites during an innate
      immune response to tissue damage and/or infection. They are finely sensitive to
      inciting stimuli to reach in great numbers and within minutes areas of
      inflammation and tissue insult. For this effective response, they can detect
      extracellular chemical gradients and move towards higher concentrations, the so
      called chemotaxis process or guided cell migration. This directed neutrophil
      recruitment is orchestrated by chemoattractants, a chemically diverse group of
      molecular guidance cues (e.g., lipids, N-formylated peptides, complement,
      anaphylotoxins and chemokines). Neutrophils respond to these guidance signals in
      a hierarchical manner and, based on this concept, they can be further subdivided
      into two groups: "end target" and "intermediary" chemoattractants, the signals of
      the former dominant over the latter. Neutrophil chemoattractants exert their
      effects through interaction with heptahelical G protein-coupled receptors (GPCRs)
      expressed on cell surfaces and the chemotactic response is mainly regulated by
      the Rho family of GTPases. Additionally, neutrophil behavior might differ and be
      affected in different complex scenarios such as disease conditions and type of
      vascular bed in specific organs. Finally, there are different mechanisms to
      disrupt neutrophil chemotaxis either associated to the resolution of inflammation
      or to bacterial escape and systemic infection. Therefore, in the present review,
      we will discuss the different molecular players involved in neutrophil
      chemotaxis, paying special attention to the different chemoattractants described
      and the way that they interact intra- and extravascularly for neutrophils to
      properly reach the target tissue.

PMID- 29350283
TI  - Epigenetic regulation of neuroblastoma development.
AB  - In recent years, technological advances have enabled a detailed landscaping of
      the epigenome and the mechanisms of epigenetic regulation that drive normal cell
      function, development and cancer. Rather than merely a structural entity to
      support genome compaction, we now look at chromatin as a very dynamic and
      essential constellation that is actively participating in the tight orchestration
      of transcriptional regulation as well as DNA replication and repair. The unique
      feature of chromatin flexibility enabling fast switches towards more or less
      restricted epigenetic cellular states is, not surprisingly, intimately connected
      to cancer development and treatment resistance, and the central role of
      epigenetic alterations in cancer is illustrated by the finding that up to 50% of
      all mutations across cancer entities affect proteins controlling the chromatin
      status. We summarize recent insights into epigenetic rewiring underlying
      neuroblastoma (NB) tumor formation ranging from changes in DNA methylation
      patterns and mutations in epigenetic regulators to global effects on
      transcriptional regulatory circuits that involve key players in NB oncogenesis.
      Insights into the disruption of the homeostatic epigenetic balance contributing
      to developmental arrest of sympathetic progenitor cells and subsequent NB
      oncogenesis are rapidly growing and will be exploited towards the development of
      novel therapeutic strategies to increase current survival rates of patients with
      high-risk NB.

PMID- 29350281
TI  - An overview of methods/techniques for the detection of Cryptosporidium in food
      samples.
AB  - Cryptosporidium is one of the most important parasitic protozoa of concern within
      the food production industry, worldwide. This review describes the evolution and
      its development, and it monitors the methodology that has been used for
      Cryptosporidium in food material since 1984, when the first publication appeared
      regarding the detection of Cryptosporidium parvum in food materials. The methods
      that are currently being used for the detection of Cryptosporidium oocysts in
      food material (mainly vegetables) and all of the other available published
      methods are discussed in this review. Generating more consistent and reliable
      data should lead to a better understanding of the occurrence, transport and fate
      of the oocysts in food material. Improvements in monitoring and developing
      effective methodology, along with food security, offer more practical
      possibilities for both the developed and developing worlds.

PMID- 29350284
TI  - A positive relationship between spring temperature and productivity in 20
      songbird species in the boreal zone.
AB  - Anthropogenic climate warming has already affected the population dynamics of
      numerous species and is predicted to do so also in the future. To predict the
      effects of climate change, it is important to know whether productivity is linked
      to temperature, and whether species' traits affect responses to climate change.
      To address these objectives, we analysed monitoring data from the Finnish
      constant effort site ringing scheme collected in 1987-2013 for 20 common songbird
      species together with climatic data. Warm spring temperature had a positive
      linear relationship with productivity across the community of 20 species
      independent of species' traits (realized thermal niche or migration behaviour),
      suggesting that even the warmest spring temperatures remained below the thermal
      optimum for reproduction, possibly due to our boreal study area being closer to
      the cold edge of all study species' distributions. The result also suggests a
      lack of mismatch between the timing of breeding and peak availability of
      invertebrate food of the study species. Productivity was positively related to
      annual growth rates in long-distance migrants, but not in short-distance
      migrants. Across the 27-year study period, temporal trends in productivity were
      mostly absent. The population sizes of species with colder thermal niches had
      decreasing trends, which were not related to temperature responses or temporal
      trends in productivity. The positive connection between spring temperature and
      productivity suggests that climate warming has potential to increase the
      productivity in bird species in the boreal zone, at least in the short term.

PMID- 29350285
TI  - Gut shuttle service: endozoochory of dispersal-limited soil fauna by gastropods.
AB  - Numerous important ecosystem functions and services depend on soil biodiversity.
      However, little is known about the mechanisms which maintain the vast belowground
      biodiversity and about the filters shaping soil community composition. Yet,
      biotic interactions like facilitation and dispersal by animals are assumed to
      play a crucial role, particularly as most soil animal taxa are strongly limited
      in their active dispersal abilities. Here, we report on a newfound interaction of
      potentially high ubiquity and importance in soil communities: the endozoochorous
      dispersal of soil fauna by gastropods. We focus on the dispersal-limited group of
      oribatid mites, one of the most diverse and abundant soil animal groups. In a
      field survey in a German riparian forest, 73% of 40 collected slugs (Arion
      vulgaris) egested a total of 135 oribatid mites, belonging to 35 species.
      Notably, 70% of the egested mites were alive and survived the gut passage through
      slugs. Similar results were found for Roman snails (Helix pomatia), indicating
      the generality of our findings across different gastropod taxa. Complementary
      laboratory experiments confirmed our field observations, revealing that oribatid
      mites are, indeed, ingested and egested alive by slugs, and that they are able to
      independently escape the faeces and colonise new habitats. Our results strongly
      indicate that gastropods may help soil organisms to disperse within habitats, to
      overcome dispersal barriers, and to reach short-lived resource patches.
      Gastropods might even disperse whole multi-trophic micro-ecosystems, a discovery
      that could have profound implications for our understanding of dispersal
      mechanisms and the distribution of soil biodiversity.

PMID- 29350286
TI  - Changes of FibroScan, APRI, and FIB-4 in chronic hepatitis B patients with
      significant liver histological changes receiving 3-year entecavir therapy.
AB  - Noninvasive fibrosis tests have been used widely for evaluation of liver fibrosis
      in patients with chronic hepatitis B (CHB). We aimed to investigate the influence
      of antiviral treatment on FibroScan, APRI, and FIB-4 in CHB patients with
      significant liver histological changes (SLHC) defined as inflammatory grade >= A2
      and/or fibrosis stage >= F2. A total of 104 CHB patients with SLHC at the
      baseline were included. FibroScan, APRI, and FIB-4 values were compared before
      and after 3-year entecavir (ETV) treatment. Liver stiffness measurement values
      decreased significantly after 3-year ETV treatment in cirrhosis group (from 13.6
      to 9.6 kPa, p = 0.018), significant fibrosis group (from 8.4 to 5.8 kPa, p =
      0.001), and mild fibrosis group (from 5.5 to 4 kPa, p < 0.001). APRI decreased
      significantly after 3-year ETV treatment in patients with cirrhosis (from 0.80 to
      0.25, p < 0.001), patients with significant fibrosis (from 0.54 to 0.24, p <
      0.001), and those with mild fibrosis (from 0.35 to 0.23, p < 0.001). FIB-4
      decreased significantly after 3-year ETV treatment in patients with cirrhosis
      (from 1.27 to 0.81, p = 0.007) and significant fibrosis (from 1.12 to 0.78, p <
      0.001), while did not decrease significantly in patients with mild fibrosis (from
      0.90 to 0.80, p = 0.389). FibroScan, APRI, and FIB-4 values decreased
      significantly after 3-year ETV treatment in CHB patients, which indicates that
      these noninvasive fibrosis tests might be useful for monitoring regression of
      liver fibrosis and assessing treatment efficacy during long-term ETV treatment.

PMID- 29350288
TI  - Correction to: Attenuation of cortical activity triggering descending pain
      inhibition in chronic low back pain patients: a functional magnetic resonance
      imaging study.
AB  - Inadvertently, the Fig. 7 was published incorrectly in the original publication
      of the article. The correct figure should be as below.

PMID- 29350287
TI  - Long non-coding RNA H19 promotes glucose metabolism and cell growth in malignant
      melanoma via miR-106a-5p/E2F3 axis.
AB  - PURPOSE: lncRNA H19 has been considered as an oncogenic lncRNA in many human
      tumours. In the present study, we identify the role and molecular mechanism of
      lncRNA H19 in melanoma. METHOD: QRT-PCR was used to detect the expression of
      lncRNA H19 and E2F3 was detected in melanoma tissues. Cell counting kit-8 (CCK8),
      representative metabolites analysis was used to explore the biological function
      of lncRNA H19, miR-106a-5p and E2F3 in melanoma cells. Bioinformatics, luciferase
      reporter assays, MS2-RIP and RNA pull-down assay was used to demonstrate the
      molecular mechanism of lncRNA H19 in melanoma. We further test the function of
      lncRNA H19 in vivo though Xenograft tumour assay. RESULTS: We found that lncRNA
      H19 was increased in melanoma tissue, and lncRNA H19 was correlated with poor
      prognosis of melanoma patients. miR-106a-5p acts as a tumour suppressor in
      melanoma by targeting E2F3. E2F3 affects the melanoma cell glucose metabolism and
      growth. We also demonstrated that lncRNA H19 may function as the sponge of miR
      106a-5p to up-regulate E2F3 expression, and consequently promote the glucose
      metabolism and growth of melanoma. CONCLUSIONS: This result elucidates a new
      mechanism for lncRNA H19 in melanoma development and provides a survival
      indicator and potential therapeutic target for melanoma patients.

PMID- 29350289
TI  - Small RNA pathways responsible for non-cell-autonomous regulation of plant
      reproduction.
AB  - In angiosperms, germline precursors and germ cells are always attached to or
      engulfed within somatic companion cells until just before fertilization. This is
      because sperm and egg cells develop as part of the multicellular gametophyte.
      Thus, the non-cell-autonomous regulation by somatic companions plays important
      roles in efficient reproduction, in addition to the cell-autonomous regulation.
      Epigenetic silencing of transposable elements is one of the central events by
      which the germline transmits the error-free genome to the next generation. This
      review focuses on small RNA-mediated epigenetic regulation of meiosis, spore
      formation and pollen development. Besides microRNA (miRNA) and small interfering
      RNA (siRNA), animals express PIWI-interacting RNA (piRNA), a germline-specific
      class of small RNAs. Plants lack piRNA-like RNAs and, instead, express unique
      classes of small RNAs: trans-acting siRNA (tasiRNA) and phased secondary siRNA
      (phasiRNA). Especially in grass species, 21- and 24-nucleotide phasiRNAs are
      abundant in anthers during premeiosis and meiosis. This review also describes
      recent progress in reproductive phasiRNA research.

PMID- 29350291
TI  - Decompressive surgery for lumbar spinal stenosis across the Atlantic: a
      comparison of preoperative MRI between matched cohorts from the US and Norway.
AB  - BACKGROUND: There are no uniform guidelines regarding when to operate for Lumbar
      Spinal Stenosis (LSS). As we apply findings from clinical research from one
      population to the next, elucidating similarities or differences provides
      important context for the validity of extrapolating clinical outcomes. The aim of
      this study was to compare the morphological severity of lumbar spinal stenosis on
      preoperative MRI in patients undergoing decompressive surgery in Boston, USA, and
      Trondheim, Norway. METHODS: In this observational retrospective study, we
      compared morphological severity on MRI before surgical treatment between two
      propensity score-matched patient populations with single or two-level symptomatic
      LSS. We assessed the radiographic severity of LSS utilizing the Schizas
      classification (grade A to D). RESULTS: Following propensity score matching,
      demographics are balanced. In the Trondheim cohort, two levels decompression were
      present in 36.2% of the patients vs. 41.9% in Boston, (p = 0.396). There was no
      significant difference in grades A to D concerning central stenosis (p = 0.075).
      When dichotomized in mild/moderate (A/B) and severe /extreme (C/D), there were no
      significant differences in the rate of levels operated for high-grade stenosis
      (C/D), 67.6% in the Boston group compare to 78.1% in the Trondheim group (p =
      0.088). CONCLUSIONS: Trondheim, Norway, and Boston, US, have similar radiographic
      thresholds of LSS for offering surgery.

PMID- 29350292
TI  - Disc herniation, occult on preoperative imaging but visualized microsurgically,
      as the cause of idiopathic thoracic spinal cord herniation.
AB  - Idiopathic spinal cord herniation (ISCH) through an anterior dural defect is rare
      and the cause is uncertain. Recently, through interpreting imaging studies, disc
      herniation was proposed to be a major cause for ISCH. We describe the case of a
      50-year-old woman with progressive myelopathy who was diagnosed with a thoracic
      spinal cord herniation. Microsurgical exploration revealed an anterior vertical
      dural defect and a small concomitant disc herniation, occult on the preoperative
      imaging, which caused the dural defect and led to ISCH. This intraoperative
      finding corroborates the emerging notion that disc herniation is the underlying
      cause of ISCH.

PMID- 29350290
TI  - The microbiology and treatment of human mastitis.
AB  - Mastitis, which is generally described as an inflammation of breast tissue, is a
      common and debilitating disease which frequently results in the cessation of
      exclusive breastfeeding and affects up to 33% of lactating women. The condition
      is a primary cause of decreased milk production and results in organoleptic and
      nutritional alterations in milk quality. Recent studies employing culture
      independent techniques, including metagenomic sequencing, have revealed a loss of
      bacterial diversity in the microbiome of mastitic milk samples compared to
      healthy milk samples. In those infected, the pathogens Staphylococcus aureus,
      Staphylococcus epidermidis and members of corynebacteria have been identified as
      the predominant etiological agents in acute, subacute and granulomatous mastitis,
      respectively. The increased incidence of antibiotic resistance in the causative
      species is also a key cause of concern for treatment of the disease, thus leading
      to the need to develop novel therapies. In this respect, probiotics and
      bacteriocins have revealed potential as alternative treatments.

PMID- 29350294
TI  - Biocatalysis of aromatic benzyl-propionate ester by different immobilized
      lipases.
AB  - Benzyl propionate is an aromatic ester that possesses a fruity odor and is
      usually found in nature in the composition of some fruits such as plums and
      melons. This work aimed for the benzyl propionate synthesis by esterification
      using a new immobilized enzyme preparation with low-cost material from Candida
      antarctica (NS 88011) and three commercial immobilized lipases (Novozym 435,
      Lipozyme TL-IM and Lipozyme RM-IM). Novozym 435 had the best performance even
      when the solvent tert-butanol was absent of the reaction medium. Results from a
      22 factorial design showed that an increase in the enzyme amount led to a higher
      conversion, even when the temperature was kept at the low value. Currently, no
      research had synthesized successfully benzyl propionate via esterification
      mediated by lipases; and we reached an ester conversion of ~ 44% after 24 h
      indicating that it is a promising route for benzyl propionate biotechnological
      production.

PMID- 29350293
TI  - Diversity and enzymatic potentialities of Bacillus sp. strains isolated from a
      polluted freshwater ecosystem in Cuba.
AB  - Genotypic and phenotypic characterization of Bacillus spp. from polluted
      freshwater has been poorly addressed. The objective of this research was to
      determine the diversity and enzymatic potentialities of Bacillus spp. strains
      isolated from the Almendares River. Bacilli strains from a polluted river were
      characterized by considering the production of extracellular enzymes using API
      ZYM. 14 strains were selected and identified using 16S rRNA, gyrB and aroE genes.
      Genotypic diversity of the Bacillus spp. strains was evaluated using pulsed field
      gel electrophoresis. Furthermore, the presence of genetic determinants of
      potential virulence toxins of the Bacillus cereus group and proteinaceous crystal
      inclusions of Bacillus thuringiensis was determined. 10 strains were identified
      as B. thuringiensis, two as Bacillus megaterium, one as Bacillus pumilus and one
      as Bacillus subtilis. Most strains produced proteases, amylases, phosphatases,
      esterases, aminopeptidases and glucanases, which reflect the abundance of
      biopolymeric matter in Almendares River. Comparison of the typing results
      revealed a spatio-temporal distribution among B. thuringiensis strains along the
      river. The results of the present study highlight the genotypic and phenotypic
      diversity of Bacillus spp. strains from a polluted river, which contributes to
      the knowledge of genetic diversity of Bacilli from tropical polluted freshwater
      ecosystems.

PMID- 29350295
TI  - EMS-induced mutation followed by quizalofop-screening increased lipid
      productivity in Chlorella sp.
AB  - The objective of this study was to enhance biomass and lipid productivity in
      Chlorella sp. isolate 6-4 by inducing mutagenesis with two growth inhibitors: the
      herbicide quizalofop-P-ethyl, a known inhibitor of acetyl-CoA carboxylase
      (ACCase) activity, and chemical mutagen, ethyl methanesulfonate (EMS), at
      different concentrations and length of times. The induced-mutagenized microalgae
      were screened on selective medium containing 10-100 uM quizalofop. The biomass
      yield, biomass productivity, lipid content, and lipid productivity of mutagenized
      microalgae were determined. The result showed that 100-200 mM EMS concentrations
      and 30 min incubation time were the most effective. Biomass yield and biomass
      productivity of the mutagenized microalgae E50-30-40, E100-60-40, and E100-30-60
      were statistically significant higher than those of the wild type. The
      mutagenized microalgae E100-30-60 showed that the highest biomass yield and
      biomass productivity were 111 and 110% higher than the wild type, respectively (p
      < 0.01). Lipid content and lipid productivity of the mutagenized microalgae E200
      30-40 were 59 and 53% significantly higher than the wild type, respectively. It
      should be noted that biomass productivity of the mutagenized microalgae E200-30
      40 was not significantly different from E100-30-60, meaning that this microalga
      strain exhibited highest both biomass and lipid productivity. These results
      indicated that inducing mutagenesis by EMS subsequently screening by herbicide
      could lead to enhance biomass and lipid accumulation. Therefore, this methodology
      could be used for improvement microalgae for biofuel production.

PMID- 29350296
TI  - Use of Biotechnological Devices in the Quantification of Psychophysiological
      Workload of Professional Chess Players.
AB  - Psychophysiological requirements of chess players are poorly understood, and
      periodization of training is often made without any empirical basis. For this
      reason, the aim of the present study was to investigate the psychophysiological
      response and quantify the player internal load during, and after playing a chess
      game. The participant was an elite 33 year-old male chess player ranked among the
      300 best chess players in the world. Thus, cortical arousal by critical flicker
      fusion threshold, electroencephalogram by the theta Fz/alpha Pz ratio and
      autonomic modulation by heart rate variability were analyzed. Data revealed that
      cortical arousal by critical flicker fusion threshold and theta Fz/alpha Pz ratio
      increased and heart rate variability decreased during chess game. All these
      changes indicated that internal load increased during the chess game. In
      addition, pre-activation was detected in pre-game measure, suggesting that the
      prefrontal cortex might be preparatory activated. For these reasons,
      electroencephalogram, critical flicker fusion threshold and heart rate
      variability analysis may be highly applicable tools to control and monitor
      workload in chess player.

PMID- 29350297
TI  - Microbial communities and their predicted metabolic functions in a desiccating
      acid salt lake.
AB  - The waters of Lake Magic in Western Australia are among the most geochemically
      extreme on Earth. This ephemeral saline lake is characterized by pH as low as 1.6
      salinity as high as 32% total dissolved solids, and unusually complex
      geochemistry, including extremely high concentrations of aluminum, silica, and
      iron. We examined the microbial composition and putative function in this extreme
      acid brine environment by analyzing lake water, groundwater, and sediment samples
      collected during the austral summer near peak evapoconcentration. Our results
      reveal that the lake water metagenome, surprisingly, was comprised of mostly
      eukaryote sequences, particularly fungi and to a lesser extent, green algae.
      Groundwater and sediment samples were dominated by acidophilic Firmicutes, with
      eukaryotic community members only detected at low abundances. The lake water
      bacterial community was less diverse than that in groundwater and sediment, and
      was overwhelmingly represented by a single OTU affiliated with Salinisphaera.
      Pathways associated with halotolerance were found in the metagenomes, as were
      genes associated with biosynthesis of protective carotenoids. During periods of
      complete desiccation of the lake, we hypothesize that dormancy and entrapment in
      fluid inclusions in halite crystals may increase long-term survival, leading to
      the resilience of complex eukaryotes in this extreme environment.

PMID- 29350298
TI  - Contribution of Mossbauer spectroscopy to the investigation of Fe/S biogenesis.
AB  - Fe/S cluster biogenesis involves a complex machinery comprising several
      mitochondrial and cytosolic proteins. Fe/S cluster biosynthesis is closely
      intertwined with iron trafficking in the cell. Defects in Fe/S cluster
      elaboration result in severe diseases such as Friedreich ataxia. Deciphering this
      machinery is a challenge for the scientific community. Because iron is a key
      player, 57Fe-Mossbauer spectroscopy is especially appropriate for the
      characterization of Fe species and monitoring the iron distribution. This
      minireview intends to illustrate how Mossbauer spectroscopy contributes to
      unravel steps in Fe/S cluster biogenesis. Studies were performed on isolated
      proteins that may be present in multiple protein complexes. Since a few decades,
      Mossbauer spectroscopy was also performed on whole cells or on isolated
      compartments such as mitochondria and vacuoles, affording an overview of the iron
      trafficking. This minireview aims at presenting selected applications of 57Fe
      Mossbauer spectroscopy to Fe/S cluster biogenesis.

PMID- 29350299
TI  - Mutagenicity, cytotoxic and antioxidant activities of Ricinus communis different
      parts.
AB  - Ricinus communis (castor plant) is a potent medicinal plant, which is commonly
      used in the treatment of various ailments. The present study was conducted to
      appraise the cytotoxicity and mutagenicity of R. communis along with antioxidant
      and antimicrobial activities. Cytotoxicity was evaluated by hemolytic and brine
      shrimp assays, whereas Ames test (TA98 and TA100) was used for mutagenicity
      evaluation. Plant different parts were extracted in methanol by shaking,
      sonication and Soxhlet extraction methods. The R. communis methanolic extracts
      showed promising antioxidant activity evaluated as through total phenolic
      contents (TPC), total flavonoid content (TFC), DPPH free radical inhibition,
      reducing power and inhibition of linoleic acid oxidation. R. communis seeds,
      stem, leaves, fruit and root methanolic extracts showed mild to moderate
      cytotoxicity against red blood cells (RBCs) of human and bovine. Brine shrimp
      lethality also revealed the cytotoxic nature of extracts with LC50 in the range
      of 0.22-3.70 (ug/mL) (shaking), 1.59-60.92 (ug/mL) (sonication) and 0.72-33.60
      (ug/mL) (Soxhlet), whereas LC90 values were in the range of 345.42-1695.81,
      660.50-14,794.40 and 641.62-15,047.80 ug/mL for shaking, sonication and Soxhlet
      extraction methods, respectively. R. communis methanolic extracts revealed mild
      mutagenicity against TA98 (range 1975 +/- 67 to 2628 +/- 79 revertant colonies)
      and TA100 (range 2773 +/- 92 to 3461 +/- 147 revertant colonies) strains and
      these values were 3267 +/- 278 and 4720 +/- 346 revertant colonies in case of
      TA98 and TA100 positive controls, respectively. R. communis methanolic extracts
      prevented the H2O2 and UV to Plasmid pBR322 DNA oxidative damage. Results
      revealed that R. communis is a potential source of bioactive compounds and in
      future studies the bioactive compounds will be identified by advanced
      spectroscopic techniques.

PMID- 29350300
TI  - The relationship between gait variability and cognitive functions differs between
      fallers and non-fallers in MS.
AB  - The objective of the study was to determine if cognitive function is associated
      with step time variability in people with multiple sclerosis (PwMS). The study
      included 355 PwMS (218 women), average age 41.1 (SD = 13.5), disease duration 5.9
      (SD = 7.3) years, and a median expanded disability status scale score of 2.5. We
      separately analyzed the sample group of fallers and non-fallers based on their
      fall history. Gait variability was measured by an electronic walkway and all
      participants completed a computerized cognitive test battery designed to evaluate
      multiple cognitive domains. Fallers (43.7%) demonstrated elevated step time
      variability (%CV), 5.0 (SD = 3.4) vs. 3.5 (SD = 1.6), P < 0.001 compared to the
      non-faller subjects. According to the regression analysis in the non-fallers'
      group, step time variability was found significantly associated with the global
      cognitive score (P = 0.001), executive function subcategory (P = 0.038), and
      motor skills subcategory (P < 0.001). No relationship between step time
      variability and any cognitive domain was demonstrated in the faller group. This
      study illustrated that the association between gait variability and cognition
      occurs only in PwMS without a fall history. From a clinical standpoint, these
      findings might help medical professionals to create improved assessment tests and
      rehabilitation strategies in the MS population.

PMID- 29350301
TI  - Constipation in Parkinson's Disease: a Nuisance or Nuanced Answer to the
      Pathophysiological Puzzle?
AB  - PURPOSE OF REVIEW: Chronic constipation is a common, nonmotor, and prodromal
      symptom in Parkinson's disease (PD). Its underlying neuropathology may provide
      pathophysiological insight into PD. Here, we critically review what is currently
      known about the neuroanatomical and brain-gut interactions, and the origin and
      progression of Lewy pathology (LP) at three levels-brain/brainstem, spinal cord,
      and enteric nervous system. RECENT FINDINGS: Many recent studies have illustrated
      the challenges of examining LP in tissues obtained from colon biopsies of PD
      patients. Large-scale epidemiological studies have not confirmed the widely
      accepted Braakpostula. In this review, we propose an alternative origin and route
      of spread of LP in PD. We describe novel, noninvasive neurophysiological testing
      that could advance the understanding of LP and complex bidirectional brain-pelvic
      floor neural pathways in PD-a true disease model of a neurogastrointestinal
      disorder. This review may provide the impetus for future studies investigating
      gut and brain interaction and constipation in PD.

PMID- 29350302
TI  - Antifungal mechanism of sodium dehydroacetate against Geotrichum citri-aurantii.
AB  - This study investigated the potential anti-fungal mechanisms of sodium
      dehydroacetate (SD) against Geotrichum citri-aurantii. The results showed that
      the cell wall integrity of G. citri-aurantii was not affected, whereas the
      membrane permeability of G. citri-aurantii mycelia was visibly altered by SD.
      Dramatic morphological changes of the mycelia, such as loss of cytoplasm,
      plasmolysis, and dissolution of intracellular substances, were observed by
      scanning electron microscopy and transmission electron microscopy analyses,
      indicating that the mycelium is severely damaged by the SD treatment.
      Furthermore, SD apparently induced a decrease in the intracellular ATP content
      before 30 min of exposure. An increase in the activity of the Na+/K+-ATPase was
      also observed, indicating that Na+ ions might enter the cell and thus disturb the
      energy supply. Taken together, this study's findings suggest that the anti-fungal
      activity of SD against G. citri-aurantii can be attributed to the disruption of
      cell membrane permeability and energy metabolism.

PMID- 29350303
TI  - A Short Review of the Non-invasive Transcutaneous Pericranial Electrical
      Stimulation Techniques and their Application in Headache.
AB  - PURPOSE OF REVIEW: In this short review, the most common non-invasive
      neuromodulatory techniques will be described, along with their advantages and
      disadvantages and their application in headache. Available preventive treatments
      can be unhelpful or may have unpleasant side effects; moreover, the rate of
      response to preventive drugs does not exceed 50%, lower in chronic migraine;
      alternative options would be welcome. Though the concept of neuromodulation was
      originally developed with invasive methods, newer non-invasive techniques are
      appearing. RECENT FINDINGS: The novel neuromodulatory techniques have been
      developed with encouraging results: compared with traditional pharmacotherapy,
      advantages of non-invasive neuromodulation include reduced incidence of adverse
      effects, improved adherence, and safety and ease of use. The results are
      encouraging for acute or preventive treatment of different kinds of headache. A
      variety of neuromodulatory approaches is expanding fastly and has opened new
      possibilities for treatment of patients suffering from many forms of headache,
      especially those who have failed traditional pharmacotherapy. The non-invasive
      treatments can be seen as supplementing traditional management in refractory
      patients. Current study results are encouraging but preliminary and larger and
      more rigorous trials are needed to clarify benefit and mode of action.

PMID- 29350304
TI  - Defective mitochondrial ATPase due to rare mtDNA m.8969G>A mutation-causing
      lactic acidosis, intellectual disability, and poor growth.
AB  - Mutations in mitochondrial ATP synthase 6 (MT-ATP6) are a frequent cause of NARP
      (neurogenic muscle weakness, ataxia, and retinitis pigmentosa) or Leigh
      syndromes, especially a point mutation at nucleotide position 8993. M.8969G>A is
      a rare MT-ATP6 mutation, previously reported only in three individuals, causing
      multisystem disorders with mitochondrial myopathy, lactic acidosis, and
      sideroblastic anemia or IgA nephropathy. We present two siblings with the
      m.8969G>A mutation and a novel, substantially milder phenotype with lactic
      acidosis, poor growth, and intellectual disability. Our findings expand the
      phenotypic spectrum and show that mtDNA mutations should be taken account also
      with milder, stable phenotypes.

PMID- 29350305
TI  - Percutaneous Mechanical Circulatory Support Devices for High-Risk Percutaneous
      Coronary Intervention.
AB  - PURPOSE OF REVIEW: Percutaneous mechanical circulatory support devices (PMCSD)
      consist of the intra-aortic balloon pump (IABP), Impella (Abiomed Inc., Danvers,
      Massachusetts), Tandem Heart (Cardiac Assist, Inc., Pittsburgh, Pennsylvania), or
      extracorporeal membranous oxygenation (ECMO). They augment cardiac output,
      cardiac index, and cardiac power which allow the operator to mitigate hemodynamic
      perturbations during high-risk percutaneous coronary intervention (HR-PCI). This
      review discusses PMCSD and their contemporary literature. RECENT FINDINGS: Recent
      literature has substantiated the hemodynamic benefits of PMCSD in HR-PCI and
      cardiogenic shock, but no mortality benefit was found. As stent technology
      improves, PCI is expanding into high-risk cases in which PMCSD provide
      hemodynamic support allowing safe and complete revascularization.

PMID- 29350306
TI  - Progress on the study of the mechanism of busulfan cytotoxicity.
AB  - The preparation of spermatogonial stem cell (SSC) transplant recipients laid the
      technical foundation for SSC transplant technology and the understanding of
      spermatogenesis mechanisms. Busulfan is commonly used to prepare recipients for
      mouse SSC transplantation; however, its safety and efficiency have been
      questioned. This review summarizes the relationship between SSCs and Sertoli
      cells (SCs), and the mechanism of busulfan toxicity against sperm cells. We
      concluded that the proliferation, differentiation, and apoptosis of SSCs are
      regulated by SCs. The endogenous spermatogenic cells are depleted by busulfan
      treatment via alkylation of DNA, destruction of vimentin filament distribution,
      disruption of SSC differentiation, promotion of SSC dormancy, and generation of
      oxidative stress. However, the mechanisms require further exploration. The recent
      establishment of a model in vitro culture system has provided a good technical
      foundation to further explore these mechanisms, which will help us to find more
      efficient methods of recipient preparation and optimal transplantation times.

PMID- 29350307
TI  - Living with chronic pain: perceptions of breast cancer survivors.
AB  - PURPOSE: Breast cancer treatments may lead to chronic pain. For some breast
      cancer survivors (BCS), this experience can develop into the perception of living
      with chronic pain. The majority of BCS are postmenopausal and have hormone
      receptor-positive (HR+) breast cancer requiring aromatase inhibitors (AIs).
      Neither the prevalence nor risk factors associated with the perception of living
      with chronic pain among this population are well defined. METHODS: We conducted a
      cross-sectional survey among postmenopausal, HR+ BCS who previously took or were
      currently taking AIs. The primary outcome was patients' perception of living with
      chronic pain over the past 6 months. We measured pain and demographic and
      clinical variables. Multivariable logistic regression analysis was performed to
      evaluate risk factors associated with the perception of chronic pain. RESULTS:
      Among 1280 participants, 167 (13%) reported having the perception of living with
      chronic pain before their breast cancer diagnosis; 426 (34%) reported this
      perception after completion of non-hormonal cancer treatment. Seventy-eight
      percent of BCSs reported experiencing at least one type of treatment-related pain
      within the past 7 days, with 23% experiencing at least three types. The most
      common types of pain were AI-induced musculoskeletal pain (49%) and pain at the
      surgery or radiation site (31%). Younger age (< 56), BMI > 25, and the perception
      of living with chronic pain before diagnosis were risk factors associated with
      the perception of living with chronic pain. CONCLUSIONS: One in three
      postmenopausal, HR+ BCS considered themselves to be living with chronic pain.
      Effective interventions to reduce chronic pain are needed.

PMID- 29350309
TI  - Population Genetics of the Endangered and Wild Edible Plant Ottelia acuminata in
      Southwestern China Using Novel SSR Markers.
AB  - Ottelia acuminata is an edible aquatic plant species that is endemic to
      southwestern China. This plant has experienced habitat degradation resulting from
      environmental change and extensive human disturbance. Determining the genetic
      variation and genetic structure of O. acuminata populations could help develop
      strategies to collect, evaluate, utilize and conserve the species. To this end,
      we genotyped 183 individuals sampled throughout the species distribution using
      twelve novel nuclear microsatellite loci (nSSRs). Eight of these nSSRs exhibited
      low average levels of genetic diversity (HE = 0.351, Ho = 0.376) and showed
      evidence of significant inbreeding across several populations. A high degree of
      genetic differentiation was identified among populations (FST = 0.457), probably
      resulting from limited pollen and seed-mediated gene flow. Only 17.8% of
      variation existed between O. acuminata var. acuminata and other O. acuminata
      varieties. Bayesian analysis and a UPGMA dendrogram based on Nei's genetic
      distance also revealed notably low genetic differentiation among the varieties.
      This low genetic differentiation is possibly attributed to shared ancestral
      polymorphisms since their divergence. Additional taxonomic and phylogenetic
      studies with additional molecular markers are needed to determine the population
      genetic relationship between O. acuminata varieties. Conservation of this species
      depends on in situ and ex situ actions, such as controlling habitat water
      pollution and overexploitation and creating a germplasm bank based on the
      population genetic differences. To the best of our knowledge, this study
      represents the first attempt to understand the population genetics of O.
      acuminata in China using novel nSSR markers developed from transcriptome
      sequencing and could contribute to the conservation management of this economic
      plant.

PMID- 29350308
TI  - The PPARgamma agonist efatutazone delays invasive progression and induces
      differentiation of ductal carcinoma in situ.
AB  - PURPOSE: Ductal carcinoma in situ (DCIS) is a pre-invasive lesion of the breast
      considered a precursor of invasive ductal carcinoma. This study aimed to
      determine whether activated PPARgamma acts as a tumor suppressor in human DCIS
      progression. METHODS: We utilized the high-affinity PPARgamma agonist,
      efatutazone, to activate endogenous PPARgamma in a well-defined model for the
      progression of basal (triple negative) DCIS, MCFDCIS cells, cultured under 2D and
      3D conditions. We studied the effects of activated PPARgamma on DCIS progression
      in MCFDCIS xenograft and C3(1)/Tag transgenic mice treated with 30 mg/kg of
      efatutazone. RESULTS: In vitro, efatutazone did not alter the MCFDCIS cell
      proliferation but induced phenotypic and gene expression changes, indicating that
      activated PPARgamma is able to differentiate MCFDCIS cells into more luminal and
      lactational-like cells. In addition, MCFDCIS tumorsphere formation in 3D was
      reduced by PPARgamma activation. In vivo, efatutazone-treated MCFDCIS tumors
      exhibited fat deposition along with upregulation of PPARgamma responsive genes in
      both epithelial and stromal compartments, suggesting features of milk-producing
      mammary epithelial cell differentiation. The efatutazone-treated lesions were
      less invasive with fewer CD44+/p63+ basal progenitor cells. PPARgamma activation
      downregulated Akt phosphorylation in these tumors, although the ERK pathway
      remained unchanged. Similar trends in gene expression changes consistent with
      lactational and luminal cell differentiation were observed in the C3(1)/Tag mouse
      model after efatutazone treatment. CONCLUSIONS: Our data suggest that activation
      of the PPARgamma pathway differentiates DCIS lesions and may be a useful approach
      to delay DCIS progression.

PMID- 29350310
TI  - Proanthocyanidins and the risk of prostate cancer in Italy.
AB  - Proanthocyanidins are polymers of monomeric unit flavan-3-ols with antioxidant,
      anti-inflammatory and free radical scavenging activities. We investigated the
      association between proanthocyanidin intake and prostate cancer risk through data
      that were collected between 1991 and 2002 in an Italian case-control study,
      including a total of 1,294 incident, histologically confirmed cases of prostate
      cancer and 1,451 controls admitted to hospital for acute, non-neoplastic, and non
      hormone-related diseases. We estimated odds ratios (ORs) and their 95% confidence
      intervals (CIs) using multiple logistic regression models, and computed energy
      adjusted proanthocyanidin intakes using the residual method. The ORs for the
      highest versus the lowest tertile were 0.80 (95% CI 0.83-1.00) for energy
      adjusted monomers and dimers combined, 0.72 (95% CI 0.59-0.87) for polymers with
      >= 3 mers, and 0.72 (95% CI 0.59-0.88) for total proanthocyanidins. The inverse
      relation was stronger among cases with a Gleason score >= 7, with the ORs of 0.56
      (95% CI 0.40-0.78) for monomers and dimers, 0.62 (95% CI 0.40-0.78) for polymers
      with >= 3 mers, and 0.57 (95% CI 0.42-0.77) for total proanthocyanidins. These
      risk estimates were consistent across strata of age, education, body mass index,
      and family history of prostate cancer. Our data indicate an inverse association
      between proanthocyanidins and prostate cancer risk.

PMID- 29350311
TI  - Shear wave elastography and AfirmaTM gene expression classifier in thyroid
      nodules with indeterminate cytology: a comparison study.
AB  - PURPOSE: To compare shear wave elastography (SWE) and AfirmaTM gene expression
      classifier (GEC) for diagnosis of malignancy in thyroid nodules (TNs) with
      Bethesda Classification (BC) III or IV indeterminate cytology. METHODS: This
      preliminary single-center prospective study was approved by the Institutional
      Review Board. We evaluated 151 consented patients with 151 indeterminate TNs (123
      BC III, 28 BC IV) on fine-needle aspiration biopsy (FNAB). B-mode ultrasound,
      vascularity, and SWE were performed prior to FNAB. TN stiffness was measured as
      shear wave velocity (SWV) in meters per second (m/s). The stiffest area of the TN
      was selected for SWV measurement. GEC testing was performed with a second FNAB.
      Surgery was recommended for GEC-suspicious TNs, or GEC-benign TNs with two or
      more worrisome B-mode US features. RESULTS: Surgical pathology confirmed 31
      malignant TNs. Among the GEC-suspicious group, 28 of 59 TNs were malignant. The
      SWV value of >=3.59 m/s was the best cut-off for malignancy risk based on the
      receiver operating curve (ROC). Twenty-six malignant TNs had SWV >= 3.59 m/s. The
      sensitivity and specificity for SWV >= 3.59 m/s were 83.9 and 79.2%,
      respectively. Positive predictive value (PPV) was 51.0% and negative predictive
      value (NPV) was 95.0%. For the GEC-suspicious group, sensitivity, specificity,
      PPV, and NPV were 90.3, 74.2, 47.5, and 96.7%, respectively. In multivariate
      analysis, SWV and GEC-suspicious were significant predictors of malignancy, but B
      mode features and vascularity were not. CONCLUSION: This preliminary study
      indicates that SWE and GEC are independent predictors of malignancy in TNs with
      BC III or IV.

PMID- 29350312
TI  - Genesurance Counseling: Patient Perspectives.
AB  - Genetic counselors (GCs) have reported an increase in discussion of insurance
      related, or "genesurance," topics during genetic counseling sessions. Despite
      increasing frequency, there have been no studies examining patient expectations
      of GCs in these discussions. This study aimed to explore patient expectations of
      GCs in these discussions, as well as examine factors that may impact
      expectations. A 38-item survey was administered prior to patients receiving
      prenatal or cancer genetic counseling at 11 clinic sites across UTHealth, Baylor
      College of Medicine, and Sanford Health, with 360 responses analyzed. Key
      variables were analyzed using descriptive statistics, chi-square analysis, and
      multivariate logistic regression to assess associations between factors and
      control for potential confounders. Over 75% of patients expected GCs to discuss
      genesurance topics during a genetic counseling session. The majority of patients
      (78%) expected GCs to provide an estimated out-of-pocket cost, know if a test is
      a covered benefit (77%), and provide referral information for further questions
      (76%). Two additional expectations, considered to be unrealistic in most clinical
      settings, included expecting GCs to know the patient's specific insurance plan
      and coverage information (57%) and provide an exact out-of-pocket cost (41%).
      Ethnicity was the only significant predictor of response for these two
      expectations, as African Americans and Hispanics were more likely than Caucasians
      to have these beliefs. While the patient participants felt that GCs were
      primarily responsible for initiating these conversations, they also reported a
      personal sense of responsibility for raising questions. This study demonstrates
      that patients may expect GCs to address genesurance topics in a genetic
      counseling session, with specific expectations about the cost and coverage of
      genetic tests. Further studies will establish the most effective way to
      communicate this information to patients and examine whether and where within the
      scope of GC practice, genesurance discussions fall.

PMID- 29350313
TI  - Immobilization of Methylosinus trichosporium OB3b for methanol production.
AB  - Due to the natural gas boom in North America, there is renewed interest in the
      production of other chemical products from methane. We investigated the
      feasibility of immobilizing the obligate methanotrophic bacterium Methylosinus
      trichosporium OB3b in alginate beads, and selectively inactivating methanol
      dehydrogenase (MDH) with cyclopropane to produce methanol. In batch cultures and
      in semi-continuous flow columns, the exposure of alginate-immobilized cells to
      cyclopropane or cyclopropanol resulted in the loss of the majority of MDH
      activity (> 80%), allowing methanol to accumulate to significant concentrations
      while retaining all of M. trichosporium OB3b's methane monooxygenase capacity.
      Thereafter, the efficiency of methanol production fell due to recovery of most of
      the MDH activity; however, subsequent inhibition periods resulted in renewed
      methanol production efficiency, and immobilized cells retained methane-oxidizing
      activity for at least 14 days.

PMID- 29350314
TI  - Eimeria maricopensis n. sp. (Apicomplexa: Eimeriidae) from the Arizona cotton rat
      Sigmodon arizonae Mearns (Rodentia: Cricetidae) in central Arizona, USA.
AB  - Eimeria maricopensis n. sp. (Apicomplexa: Eimeriidae) is described from 2 of 15
      (13%) Arizona cotton rats Sigmodon arizonae Mearns in Arizona, USA. Sporulated
      oocysts of this new species are ovoidal to ellipsoidal, 20-28 * 16-22 (24.9 *
      19.2) um, with a smooth, bi-layered wall; both micropyle and oocyst residuum are
      absent, but fragmented polar granule material is present. Sporocysts are
      ellipsoidal, 11-14 * 6-8 (12.9 * 7.0) um, with a Stieda body, sub-Stieda body,
      and sporocyst residuum; sporozoites are elongate with a spheroidal anterior
      refractile body and a subspheroidal posterior refractile body. In addition,
      sporulated oocysts of Eimeria sigmodontis Barnard, Ernst & Dixon, 1974, Eimeria
      tuskegeensis Barnard, Ernst & Dixon, 1974 and Eimeria webbae Barnard, Ernst &
      Dixon, 1974 are described from S. arizonae. This is the first report on the
      coccidia of S. arizonae.

PMID- 29350316
TI  - Influence of Personality and Motivation on Oral Presentation Performance.
AB  - Personality and motivation have been identified as influential variables
      associated with foreign language learning; however, few studies have investigated
      their effect on oral presentations. This study addresses the importance of both
      personality and motivation in students' collaborative oral presentation
      performance. A Big Five personality trait questionnaire measuring Extraversion,
      Agreeableness, Conscientiousness, Neuroticism and Openness to Experience,
      together with the Collaborative Inquiry-based Project Questionnaire measuring
      Task, Project Work, Reinforcement, Social Learning and Social Pressure
      motivational constructs were employed to evaluate 257 university students. In
      general, the results showed that Extraversion, Project Work and Social Pressure
      were significant correlates of oral presentation scores. The first result
      suggests that extraverts possess superiority in situations where oral language
      production is central to communication. This was particularly true for lower
      level students, inferring that extraverted personalities can compensate for a
      lower English language ability. The second indicates that the inquiry-based
      nature of the assignments was an intrinsic motivator especially valued by
      extraverts. The third implies that extrinsic motivation was a factor influencing
      student performance. These findings extend previous research by highlighting the
      contextual relationships between these affective variables and performance in
      collaborative oral presentation contexts.

PMID- 29350315
TI  - Revisiting embryo assisted hatching approaches: a systematic review of the
      current protocols.
AB  - Zona pellucida (ZP) manipulation, termed "assisted hatching" (AH), has been
      introduced in order to favor embryo hatching and ultimately improve assisted
      reproductive technology success but with poor proofs of safety and biological
      plausibility. We herein provide a systematic review of clinical outcomes
      following the application of different methods of ZP manipulation on fresh or
      frozen/thawed embryos at different developmental stages in different groups of
      patients. Out of the 69 papers that compared the clinical outcomes deriving from
      hatched versus non-hatched embryos, only 11 considered blastocysts while the rest
      referred to cleavage stage embryos. The ZP thinning of fresh embryos either by
      chemical or laser approach was shown to provide very limited benefit in terms of
      clinical outcomes. Better results were observed with procedures implying a higher
      degree of zona manipulation, including zona removal. Studies comparing the
      mechanical or chemical procedures to those laser-mediated consistently reported a
      superiority of the latter ones over the former. Literature is consistent for a
      benefit of ZP breaching in thawed blastocysts. This review provides the current
      knowledge on the AH procedure in order to improve its efficacy in the appropriate
      context. Embryologists might benefit from the approaches presented herein in
      order to improve Assisted Reproduction Technologies (ART) outcomes.

PMID- 29350317
TI  - A study on the role that quorum sensing play in antibiotic-resistant plasmid
      conjugative transfer in Escherichia coli.
AB  - Horizontal genes transfer (HGT) plays an important role in the dissemination of
      antibiotic resistance genes (ARGs) in the environment. However, the mechanisms of
      HGT of ARGs under the influence of antibiotics in sub-MIC remain rarely explored.
      Moreover, given its collective nature, HGT was considered to be relative to
      quorum sensing (QS) system. To investigate whether QS has any impact on
      horizontal gene transfer of ARGs, experiments were conducted to determine the
      conjugative efficiency of plasmid RP4 on Escherichia coli (E.coli) under the
      influences of tetracyclines (TCs), quorum sensing autoinducers (AIs) and quorum
      sensing inhibitors (QSIs). The results indicated that the sub-MIC TCs could
      facilitate the conjugative transfer of RP4, a process which could be enhanced by
      AIs but inhibited by QSIs. This study demonstrated the roles that QS played in
      the dissemination of ARGs, and provided theoretical insights into the mechanism
      of HGT of ARGs in the environment.

PMID- 29350318
TI  - Father Absence, Social Networks, and Maternal Ratings of Child Health: Evidence
      from the 2013 Social Networks and Health Information Survey in Mexico.
AB  - Objectives To bridge the literature on the effect of father absence,
      international migration, and social networks on child health, we assess the
      association between father absence and maternal ratings of child poor health
      (MCPH). Next we test whether social networks of immediate and extended kin
      mediate the relationship between fathers' absence and MCPH. Methods Nested
      logistic regression models predicting MCPH are estimated using the 2013 Social
      Networks and Health Information Survey, collected in a migrant-sending community
      in Guanajuato, Mexico. These unique data distinguish among father absence due to
      migration versus other reasons and between immediate and extended kin ties.
      Results Descriptive results indicate that 25% of children with migrant fathers
      are assessed as having poor health, more often than children with present (15.5%)
      or otherwise absent fathers (17.5%). In the multivariate models, fathers' absence
      is not predictive of MCPH. However, the presence of extended kin ties for the
      mother was associated with approximately a 50% reduction in the odds of MCPH.
      Additionally, mother's poor self-assessed health was associated with increased
      odds of MCPH while the presence of a co-resident adult lowered the odds of MCPH.
      In sensitivity analysis among children with migrant fathers, the receipt of
      paternal remittances lowered the odds of MCPH. Conclusions for Practice Social
      networks have a direct and positive association with MCPH rather than mediating
      the father absence-MCPH relationship. The presence of extended kin ties in the
      local community is salient for more favorable child health and should be
      considered in public health interventions aimed at improving child health.

PMID- 29350319
TI  - Complexity of Resiliency Framework for Refugee Population: A Letter to the Editor
      Regarding Wright et al. (2016).

PMID- 29350320
TI  - Ethical Implications in Vaccine Pharmacotherapy for Treatment and Prevention of
      Drug of Abuse Dependence.
AB  - Different immunotherapeutic approaches are in the pipeline for the treatment of
      drug dependence. "Drug vaccines" aim to induce the immune system to produce
      antibodies that bind to drugs and prevent them from inducing rewarding effects in
      the brain. Drugs of abuse currently being tested using these new approaches are
      opioids, nicotine, cocaine, and methamphetamine. In human clinical trials,
      "cocaine and nicotine vaccines" have been shown to induce sufficient antibody
      levels while producing few side effects. Studies in humans, determining how these
      vaccines interact in combination with their target drug, are underway. However,
      although vaccines can become a reasonable treatment option for drugs of abuse,
      there are several disadvantages that must be considered. These include i) great
      individual variability in the formation of antibodies, ii) the lack of protection
      against a structurally dissimilar drug that produces the same effects as the drug
      of choice, and iii) the lack of an effect on the drug desire that may predispose
      an addict to relapse. In addition, a comprehensive overview of several crucial
      ethical issues has not yet been widely discussed in order to have not only a
      biological approach to immunotherapy of addiction. Overall, immunotherapy offers
      a range of possible treatment options: the pharmacological treatment of
      addiction, the treatment of overdoses, the prevention of toxicity to the brain or
      the heart, and the protection of the fetus during pregnancy. So far, the results
      obtained from a small-scale experiment using vaccines against cocaine and
      nicotine suggest that a number of important technical challenges still need to be
      overcome before such vaccines can be approved for clinical use.

PMID- 29350321
TI  - Sliding to predict: vision-based beating heart motion estimation by modeling
      temporal interactions.
AB  - PURPOSE: Technical advancements have been part of modern medical solutions as
      they promote better surgical alternatives that serve to the benefit of patients.
      Particularly with cardiovascular surgeries, robotic surgical systems enable
      surgeons to perform delicate procedures on a beating heart, avoiding the
      complications of cardiac arrest. This advantage comes with the price of having to
      deal with a dynamic target which presents technical challenges for the surgical
      system. In this work, we propose a solution for cardiac motion estimation.
      METHODS: Our estimation approach uses a variational framework that guarantees
      preservation of the complex anatomy of the heart. An advantage of our approach is
      that it takes into account different disturbances, such as specular reflections
      and occlusion events. This is achieved by performing a preprocessing step that
      eliminates the specular highlights and a predicting step, based on a conditional
      restricted Boltzmann machine, that recovers missing information caused by partial
      occlusions. RESULTS: We carried out exhaustive experimentations on two datasets,
      one from a phantom and the other from an in vivo procedure. The results show that
      our visual approach reaches an average minima in the order of magnitude of
      [Formula: see text] while preserving the heart's anatomical structure and
      providing stable values for the Jacobian determinant ranging from 0.917 to 1.015.
      We also show that our specular elimination approach reaches an accuracy of 99%
      compared to a ground truth. In terms of prediction, our approach compared
      favorably against two well-known predictors, NARX and EKF, giving the lowest
      average RMSE of 0.071. CONCLUSION: Our approach avoids the risks of using
      mechanical stabilizers and can also be effective for acquiring the motion of
      organs other than the heart, such as the lung or other deformable objects.

PMID- 29350322
TI  - Do telehealth interventions improve oral anticoagulation management? A systematic
      review and meta-analysis.
AB  - The benefits and harms of telehealth interventions compared to usual care for
      oral anticoagulation management are unclear. A systematic review and meta
      analysis was conducted to assess their impact on clinically important outcomes. A
      search was conducted through MEDLINE, EMBASE and CENTRAL databases, and the
      retrieved citations were independently screened and extracted by two review
      authors. Cochrane Collaboration-recommended tools were used to assess for risk of
      bias. Co-primary outcomes were major bleeding and major thromboembolic events. Of
      2145 retrieved citations, 7 were included for qualitative synthesis (1 randomized
      controlled trial, 1 prospective cohort and 5 retrospective cohorts). None
      addressed direct oral anticoagulants. Telehealth interventions were mainly
      consisted of telephone visits by clinicians, pharmacists and specialists. Meta
      analysis of 3 studies (n = 6955) showed significant improvements in the
      telehealth group for major thromboembolic events (RR 0.43, 95% CI 0.25-0.74, p =
      0.002), but no significant difference for major bleeding events (RR 0.83, 95% CI
      0.52-1.33, p = 0.44). There was no significant difference in any of the secondary
      outcomes. The overall GRADE quality of evidence was rated very low due to high
      risk of bias and low precision. Based on very low quality evidence, telehealth
      interventions may lower the risk of major thromboembolic events, but not other
      clinically important outcomes. A high quality study is likely to strongly
      influence these results. High quality randomized trials are recommended to better
      assess the benefits and harms of telehealth interventions for anticoagulation
      management.

PMID- 29350323
TI  - William E. Vidaver (1921-2017): an innovator, enthusiastic scientist, inspiring
      teacher and a wonderful friend.
AB  - William (Bill) E. Vidaver (February 2, 1921-August 31, 2017), who did his Ph.D.
      with Laurence (Larry) R. Blinks at Stanford (1964) and a postdoc with C. Stacy
      French (1965), taught and did research at Simon Fraser University (SFU) for
      almost 30 years. Here he published over 80 papers in photosynthesis-related areas
      co-authored by his graduate students, postdocs, visiting professors and SFU
      colleagues. He developed a unique high-pressure cuvette for the study of oxygen
      exchange and studied high-pressure effects in photosynthesis. Ulrich (Uli)
      Schreiber, as a postdoctoral fellow from Germany, introduced measurements on
      chlorophyll (Chl) a fluorescence to Bill's lab, leading to the discovery of
      reversible inhibition of excitation energy transfer between photosynthetic
      pigments and of a pivotal role of O2 in the oxidation of the electron transport
      chain between Photosystem II (PS II) and PS I. Bill's and Uli's work led to a
      patent of a portable chlorophyll fluorometer, the first available commercially,
      which was later modified to measure whole plantlets. The latter was used in
      pioneering measurement of the health of forest and crop plants undergoing in
      vitro clonal micropropagation. With several other researchers (including Doug
      Bruce, the late Radovan Popovic, and Sarah Swenson), he localized the quenching
      site of O2 and showed a dampening effect on measurements of the four-step process
      of O2 production by endogenous oxygen uptake. Bill is remembered as a hard
      working but fun-loving person with a keen mind and strong sense of social
      justice.

PMID- 29350324
TI  - Evolving Landscape of Clinical Trials in Heart Failure: Patient Populations,
      Endpoint Selection, and Regions of Enrollment.
AB  - PURPOSE OF REVIEW: Clinical trial design and execution are evolving as
      increasingly important considerations with respect to the success of heart
      failure trials. The current review highlights temporal trends in characteristics
      of heart failure clinical trials. RECENT FINDINGS: Recent trials in heart failure
      have required longer recruitment phases, displayed inefficient enrollment rates,
      increased use of composite and nonfatal endpoints, undergone rapid globalization,
      and gradually increased focus on heart failure with preserved ejection fraction.
      Understanding patterns and trends in clinical trial design and execution may
      inform future planning and conduct of trials of heart failure therapeutics.

PMID- 29350325
TI  - Evaluation and Management of Rotator Cuff Tears: a Primary Care Perspective.
AB  - PURPOSE OF REVIEW: To provide a primary care perspective regarding the evaluation
      and management of shoulder pain and rotator cuff tears. RECENT FINDINGS: In the
      primary care setting, rotator cuff pathology is commonly encountered. Information
      regarding the risks of oral medications for the management of the associated pain
      keeps mounting. Partial-thickness rotator cuff tears remain difficult to diagnose
      with a single imaging modality. Musculoskeletal education in medical schools and
      non-orthopaedic residency and fellowship training programs continues to be an
      area for additional improvement. In the primary care office, the initial
      evaluation of shoulder pain should include a thorough musculoskeletal evaluation
      in order to identify the source of the pain (e.g., shoulder, cervical spine,
      chest wall), as well as the development of an initial treatment plan. Access to
      imaging modalities such as ultrasound and MRI can vary depending on the resources
      available in the primary care setting. The identification of patients who may
      benefit from early surgical referral is imperative for optimizing outcomes.

PMID- 29350326
TI  - Oxyresveratrol prevents murine H22 hepatocellular carcinoma growth and lymph node
      metastasis via inhibiting tumor angiogenesis and lymphangiogenesis.
AB  - The purpose of this study was to investigate the effects and mechanisms of
      oxyresveratrol (Oxyres) on hepatocellular carcinoma (HCC) in vitro and in vivo.
      The MTT and Transwell assays were performed to investigate the effects of Oxyres
      on cell proliferation and migration of two HCC cell lines, QGY-7701 and SMMC-7721
      cells. H22 cells were subcutaneously injected into hind foot pads of 70 male mice
      to establish a lymph node metastasis model. These mice were randomly divided into
      seven groups as follows, control group, HCC group, Oxyres 20 mg/kg group, Oxyres
      40 mg/kg group, Oxyres 60 mg/kg group, Resveratrol (Res) group, and Adriamycin
      (ADM) group. Oxyres, Res, and ADM were intraperitoneally injected daily for
      consecutive 21 days. Tumors and popliteal lymph node were isolated and embedded
      for histology analysis. Expressions of CD31 and vascular endothelial growth
      factor receptor-3 (VEGFR3) in tumors were detected by immunohistocehmistry.
      Expressions of vascular endothelial growth factor C (VEGF-C) were measured by
      Western blot. Oxyres significantly inhibited the proliferation and migration of
      QGY-7701 and SMMC-7721 cells. Oxyres significantly inhibited tumor growth (p <
      0.001) and metastasis to sentinel lymph nodes (70%) in a dose-dependent manner.
      Oxyres showed a similar inhibition rate as Res. Oxyres also significantly
      decreased micro-blood vessel density and micro-lymphatic vessel density in tumors
      (p < 0.05). Expressions of CD31, VEGFR3, and VEGF-C of tumors were also inhibited
      by Oxyres (p < 0.05). Oxyres exerts anti-tumor effects against HCC through
      inhibiting both angiogenesis and lymph node metastasis, which suggests Oxyres be
      a potential therapeutic agent.

PMID- 29350327
TI  - Hypermutated Tumors and Immune Checkpoint Inhibition.
AB  - Microsatellite instability-high/DNA mismatch repair deficient tumors are found
      across the cancer spectrum and often harbor markedly increased numbers of
      mutations when compared to microsatellite stable/DNA mismatch repair proficient
      tumors. As a result of this high mutational load, tumor-infiltrating lymphocyte
      density is increased and more immunogenic neoepitopes are expressed, leading to
      upregulation of immune checkpoints in these tumors. Checkpoint inhibitors such as
      pembrolizumab and nivolumab, both immunoglobulin G4 (IgG4) monoclonal antibodies
      that block interactions between the programmed cell death receptor-1 and its
      ligands, have significant activity in this tumor class. This review will focus on
      hypermutated tumors and immuno-oncology drug development for this biologically
      unique tumor type, with an emphasis on FDA-approved immunotherapies for these
      cancers, as well as a short discussion of the many therapeutic and scientific
      challenges ahead in order to optimize the uses of this new class of drug.

PMID- 29350328
TI  - Uyghur Text Matching in Graphic Images for Biomedical Semantic Analysis.
AB  - How to read Uyghur text from biomedical graphic images is a challenge problem due
      to the complex layout and cursive writing of Uyghur. In this paper, we propose a
      system that extracts text from Uyghur biomedical images, and matches the text in
      a specific lexicon for semantic analysis. The proposed system possesses following
      distinctive properties: first, it is an integrated system which firstly detects
      and crops the Uyghur text lines using a single fully convolutional neural
      network, and then keywords in the lexicon are matched by a well-designed matching
      network. Second, to train the matching network effectively an online sampling
      method is applied, which generates synthetic data continually. Finally, we
      propose a GPU acceleration scheme for matching network to match a complete Uyghur
      text line directly rather than a single window. Experimental results on benchmark
      dataset show our method achieves a good performance of F-measure 74.5%. Besides,
      our system keeps high efficiency with 0.5s running time for each image due to the
      GPU acceleration scheme.

PMID- 29350329
TI  - Detection of human papillomavirus DNA in tumors from Rwandese breast cancer
      patients.
AB  - BACKGROUND: During the last decades, a great interest was given to viral etiology
      of breast cancer. Indeed, due to recent technical improvements and some
      encouraging new results, it has been a resurgence of interest in the possibility
      that a substantial proportion of human breast cancers may be caused by viral
      infections. High-risk genotypes of human papillomavirus (HPV) have been found in
      breast cancer cases. In the present study, we aimed to assess the presence of HPV
      DNA in breast cancer cases from Rwanda and to evaluate the association between
      HPV infection and clinico-pathological features. METHODS: Therefore, a total of
      47 archived formalin-fixed paraffin-embedded biopsies were collected and complete
      information was recorded. HPV detection and genotyping were done by PCR
      amplification and DNA sequencing. RESULTS: Overall, HPV DNA was found in 46.81%
      of cases, HPV16 being the most prevalent subtype (77.27%) followed by HPV33
      (13.64%) and HPV31 (9.09%). Comparison of HPV with clinico-pathological features
      showed no significant difference between HPV infection and breast localization,
      histological subtype, clinical stage, tumor grade, and intrinsic molecular
      subtypes. CONCLUSIONS: These findings provide evidence of high prevalence of high
      risk HPV in Rwandese patients with breast cancer and suggest that high-risk HPV
      infections could be a risk factor associated with human breast cancer
      development.

PMID- 29350330
TI  - Role of dual-energy CT in the diagnosis and follow-up of gout: systematic
      analysis of the literature.
AB  - The aim of this systematic review was to determine the potential role of dual
      energy CT in the diagnosis and follow-up of gout with regard to the Outcome
      Measures in Rheumatology (OMERACT) filter. A systematic analysis of the
      literature was conducted using the MEDLINE and Cochrane databases and published
      abstracts of international congresses, according to the criteria of the OMERACT
      filter: feasibility, reproducibility, validity versus laboratory (serum urate,
      MSU synovial fluid aspirate) and other imaging modalities for gout, and its
      sensitivity to change in patients on urate lowering therapy (ULT). Thirty-two
      articles were found representing a total of 1502 patients. The data on
      feasibility showed that the examination took little time and involved low levels
      of radiation but had current limited availability. Intra- and inter-observer
      reproducibility was excellent, with intra-class correlation coefficients > 0.9.
      Validity in comparison with polarized-light microscopy showed good sensitivity
      and specificity (> 80%). The diagnostic performance was better than that of
      radiography and conventional CT-scan and at least equivalent to that of
      ultrasonography. The sensitivity to change varied with effect sizes from 0.05
      (low) to 1.24 (high) for decrease in the tophus volume following different ULT in
      gout patients. Dual-energy CT-scan is a reproducible and accurate imaging
      modality for the diagnosis of gout, particularly for tophaceous gout (intra- or
      extra-articular). It can become a second-line imaging modality of choice in cases
      of diagnostic doubt, such as ultrasonography. Its role remains uncertain in the
      follow-up of gout patients treated with ULT and needs further clarification.

PMID- 29350331
TI  - Motion deficit in nodal interphalangeal joint osteoarthritis by digital
      goniometer in housewives.
AB  - Range of motion (ROM) measured objectively in nodal hand osteoarthritis (NHOA) is
      missing. Evaluation of collateral ligaments by ultrasound (US) is unknown in NHOA
      also. To compare ROM in interphalangeal joints in housewives with nodal OA, with
      a control group by a digital system using angle to voltage (Multielgon). The
      second objective was to assess correlation between collateral radial and ulnar
      ligaments thickness and ROM. For this cross-sectional observational study, we
      assessed 60 hands with symptomatic NHOA and 30 hands of healthy housewives
      matched for age. We obtained clinical and demographic characteristics (a complete
      standardized physical examination of hand joints, DASH questionnaire, pain
      surveys, gross grasp hand goniometer, and ROM measurements by Multielgon.
      Presence of synovitis, power Doppler signal, osteophytes, and collateral
      ligaments thickness was evaluated by US. We used descriptive statistics, Spearman
      correlation, X2 test, t test and odds ratio. Significant less gross grasp and ROM
      in the right hand were observed in NHOA (p = 0.01 for both). Presence of OA,
      painful joints, disease duration, and score DASH were significant correlated with
      reduced ROM (OR 4.12, 4.12, 1.04 and 1.09, respectively). Reduced ROM was
      statistical significant in thumb MCP and IP joints, second and third DIP in
      dominant hand. There was no association between collateral radial and ulnar
      ligaments and reduced ROM. Synovitis and osteophytes were more prevalent in OA
      group. Multielgon demonstrated the pattern of reduced ROM in nodal OA of
      housewives particularly in MCP and IP thumb joints, second and third distal
      interphalangeal joints.

PMID- 29350332
TI  - Sleep in ankylosing spondylitis and non-radiographic axial spondyloarthritis:
      associations with disease activity, gender and mood.
AB  - The study aims were to assess the prevalence of good or poor sleep in a cohort of
      axial spondyloarthritis patients and to investigate its correlation with a range
      of objectively and subjectively measured variables in order to develop a model
      for distinguishing good from poor sleepers. Five hundred ninety-eight patients
      with ankylosing spondylitis and 61 with non-radiographic axial spondyloarthritis
      completed the Jenkins Sleep Evaluation Questionnaire. Measures of disease
      activity, mobility, function, mood, fatigue, quality of life, work productivity,
      night-time pain and general health were gathered. Patients with ankylosing
      spondylitis or non-radiographic axial spondyloarthritis were initially compared.
      With the exception of waking up tired less often and having lower mobility and
      functioning, the two groups were similar so were combined for subsequent
      analysis. Twenty-nine percent of all patients were classified as good sleepers
      and 19% as poor sleepers. Poor sleepers had higher disease activity and fatigue
      scores and more night-time back pain than good sleepers. They reported poorer
      quality of life, general health, mood and work-related measures. A model
      incorporating mood, gender, fatigue and objective and subjective judgements of
      disease activity correctly classified 87.3% of good and poor sleepers. Poor sleep
      was strongly associated with poor mood, female gender, greater fatigue, greater
      disease activity (specifically, spinal pain and stiffness) and better mobility;
      however, the direction of causality between poor sleep and markers of active
      disease was undetermined. This study also highlights the need to standardise the
      measurement of sleep disturbance in axSpA to facilitate comparisons between
      patient groups and interventions.

PMID- 29350333
TI  - Deltoid muscle morphometry as an index of impaired skeletal muscularity in
      neonatal intensive care.
AB  - : We hypothesised that extremely premature infants would have decreased muscle
      mass at term-corrected age compared to term-born infants and that the degree of
      reduced muscle mass acquisition would correlate with the duration of invasive
      mechanical ventilation. The MRI brain scans of infants admitted in the neonatal
      unit at King's College Hospital between 1 January 2010 and 1 June 2016 were
      retrospectively reviewed. The coronal cross-sectional area of the left deltoid
      muscle (DCSA) was measured in 17 infants born < 28 weeks of gestation and in 20
      infants born at term. The prematurely born infants had a median (IQR) gestation
      age of 25 weeks (24-27) and the term infants 40 weeks (38-41). The duration of
      invasive mechanical ventilation for the prematurely born infants was 39 days (14
      62) and that for the term infants 4 days (2-5), p < 0.001. DCSA was smaller in
      prematurely born infants (median 189, IQR 176-223 mm2) compared to term-born
      infants (median 302, IQR 236-389 mm2), p < 0.001. DCSA was related to gestation
      age (r = 0.545, p = 0.001), weight z-score at MRI (r = 0.658, p < 0.001) and days
      of invasive mechanical ventilation (r = - 0.583, p < 0.001). In conclusion,
      extremely premature infants studied at term had a lower muscle mass compared to
      term-born infants. CONCLUSION: Our results suggest that prolonged mechanical
      ventilation in infants admitted in neonatal intensive care is associated with
      reduced skeletal muscle mass acquisition. What is Known: * Prolonged mechanical
      ventilation in adult intensive care patients has been associated with skeletal
      muscle dysfunction and atrophy. * The cross-sectional area of the deltoid muscle
      has been used to evaluate muscle atrophy in infants with a previous branchial
      plexus birth injury. What is New: * Premature infants studied at term exhibit
      lower cross-sectional area of the deltoid muscle than their term counterparts. *
      Prolonged mechanical ventilation could be associated with skeletal muscle
      impairment.

PMID- 29350334
TI  - The triglyceride-glucose index, an insulin resistance marker in newborns?
AB  - : The study aims to assess the utility of the triglyceride-glucose index (TyG) as
      a marker of insulin resistance (IR) in neonates. TyG and the homeostatic model
      assessment (HOMA-IR) values were compared in 196 singleton, term normoweight and
      without distress newborns. A Decision Tree procedure (CHAID) was used to classify
      cases into groups or predict values of a dependent (Ln HOMA-IR) variable. Three
      nodes were drawn for TyG: <= 6.7, > 6.7-7.8 and > 7.8 (p < 0.0001; F = 20.52).
      The predictability of those TyG values vs HOMA-IR was statistically significant
      (p < 0.0001). It was neither affected by gender (p = 0.084), glucose challenge
      test (p = 0.138) classifications nor by the TyG node* glucose challenge test and
      TyG node*gender interactions (p = 0.456 and p = 0.209, respectively). Glucose,
      HOMA-IR, and the triglyceride/HDL cholesterol ratio increased progressively from
      node 1 to 3 for TyG while QUICKI decreased. CONCLUSION: In conclusion, TyG
      appears to be a suitable tool for identifying IR at birth, justifying the further
      insulin determination in those neonates. TyG >= 7.8 is recommended as cut-off
      point in neonates. The need for a follow-up study to confirm the TyG as early IR
      marker is desirable. WHAT IS KNOWN: * HOMA-IR and the triglyceride-glucose index
      (TyG) show a high correlation. * The TyG has been used as an insulin resistance
      marker in adults. WHAT IS NEW: * This is the first study where TyG has been
      assessed in neonates. * TyG appears to be a suitable and cheap tool for
      identifying insulin resistance at birth.

PMID- 29350336
TI  - Brain Over Bladder: A Systematic Review of Dual Cholinesterase Inhibitor and
      Urinary Anticholinergic Use.
AB  - BACKGROUND: Case reports have demonstrated that dual use of cholinesterase
      inhibitors (ChIs) and urinary anticholinergics (UAChs) in older adults may be
      associated with delusions, aggression, changes in cognition, and anxiety, which
      typically resolve on drug discontinuation. Despite opposing mechanisms of action,
      these drugs continue to be co-prescribed. OBJECTIVE: This systematic review
      evaluates cognitive and functional outcomes of dual use of ChIs and UAChs and
      describes its prevalence. PATIENTS AND METHODS: A literature search using terms
      related to ChIs and UAChs was conducted. Observational or interventional studies
      evaluating cognitive or functional outcomes in subjects receiving dual therapy
      were included for the primary aim. Articles describing prevalence of dual use
      were included for the secondary aim. RESULTS: Of 1340 unique results, five
      studies met the inclusion criteria for the primary aim. Four of the studies
      assessed cognitive outcomes-three failed to identify a significant difference in
      cognitive function with dual use and the fourth study observed a statistically
      significant improvement in cognition with dual use of high-dose donepezil and
      solifenacin when compared with baseline. Three studies assessed functional
      outcomes-one revealed a 50% greater quarterly decline in activities of daily
      living (p = 0.01) among dual users functioning in the top quartile, another
      revealed significant functional improvement in dual users, and the final study
      did not demonstrate a significant difference. Seventeen articles were included
      for the secondary aim. Prevalence of dual use ranged from 1.2 to 40.5%.
      CONCLUSION: This systematic review revealed a high prevalence of dual use of ChIs
      and UAChs; however, there are mixed results for cognitive and functional
      outcomes. Results were limited by methodological flaws. Observational or
      interventional studies assessing dual users are lacking and further study of
      cognitive and functional risks of dual ChI and UACh use is needed.

PMID- 29350335
TI  - Tools for Assessment of the Appropriateness of Prescribing and Association with
      Patient-Related Outcomes: A Systematic Review.
AB  - BACKGROUND: There are tools and criteria in the literature aimed at
      distinguishing between appropriate and inappropriate medicines use. However, many
      have not been externally validated with regard to patient-related outcomes,
      potentially limiting their use in clinical practice. OBJECTIVES: The aim of the
      study was to conduct a systematic review to summarise (1) available prescribing
      appropriateness assessment tools and criteria, and (2) their associations with
      patient-related outcomes (external validity). METHODS: A systematic review was
      conducted using MEDLINE, EMBASE and Informit (Health Collection) databases to
      screen for articles in English that examined (1) tools to assess the
      appropriateness of prescribing and (2) associations of tools with patient-related
      outcomes, published between 2000 and 2016, without any limits placed on the study
      design, participant age or setting. RESULTS: After screening 1710 articles,
      removing duplicates and shortlisting relevant articles, 42 prescribing assessment
      tools were identified. Out of the 42 tools, 78.6% (n = 33) provided guidance
      around stopping inappropriate medications, 28.6% (n = 12) around starting
      appropriate medications, 61.9% (n = 26) were explicit (criteria based) and 31.0%
      (n = 13) had been externally validated, with hospitalisation being the most
      commonly used patient-related outcome (n = 9, 21.4%). CONCLUSION: The results of
      this systematic review highlight the need for evidence-based and externally
      validated tools, which combine the different aspects of medication management to
      optimise patient-related outcomes. PROSPERO registration number: CRD42017067233.

PMID- 29350337
TI  - Baseline Neurocognitive Functioning Predicts Viral Load Suppression at 1-Year
      Follow-Up Among Newly Diagnosed HIV Infected Patients.
AB  - The current prospective observational study evaluated the impact of baseline
      neurocognitive impairment on future viral load suppression among antiretroviral
      medication naive persons newly diagnosed with HIV infection. We used the Montreal
      Cognitive Assessment (MoCA) score less than 26, to identify patients with
      neurocognitive deficits. Of the 138 patients enrolled; virologic suppression was
      seen in 61% of the participants, while 72% of the participants had a MoCA score
      less than 26 at baseline. Variables significantly associated with low MoCA score
      included higher age (p < 0.01) and presence of depression (p < 0.01). After
      adjusting for these variables, MoCA score less than 26 was significantly
      associated with a higher risk of failing achieve viral load suppression (adjusted
      OR 2.7; 95% CI 1.09-6.69). Baseline neurocognitive deficit as measured by MoCA
      was associated with a higher risk for failing to achieve viral load suppression
      at one-year follow-up.

PMID- 29350338
TI  - Reversible Suppression of Lymphoproliferation and Thrombocytopenia with Rapamycin
      in a Patient with Common Variable Immunodeficiency.

PMID- 29350339
TI  - Emerging Insights into the Esophageal Microbiome.
AB  - PURPOSE OF REVIEW: Analysis of the esophageal microbiome remains a relatively new
      field of research, and most studies to date have focused on characterizing the
      esophageal microbiome in states of health and disease. Microbiome alterations
      have been implicated in the pathogenesis of inflammatory and neoplastic
      conditions in the colon and elsewhere in the gastrointestinal tract. The
      epidemiology of various esophageal conditions including Barrett's esophagus (BE),
      esophageal adenocarcinoma (EAC), esophageal squamous cell carcinoma (ESCC), and
      eosinophilic esophagitis (EoE) point to the microbiome as a potential co-factor
      in disease pathogenesis, and the possibility exists that these microbiome
      alterations could contribute directly to the inflammatory environments necessary
      for the carcinogenesis or atopy involved in these conditions. RECENT FINDINGS:
      The native esophageal microbiome is similar in composition to the oral
      microbiome, with a high relative abundance of the phylum Firmicutes and the genus
      Streptococcus. Limited studies to date suggest that there are certain microbiome
      alterations associated with esophageal diseases. Additionally, it may be possible
      to indirectly assess the esophageal microbiome via non-endoscopic means. This
      raises the possibility that non-invasive microbiome analysis could be used for
      disease screening and monitoring. Further understanding of the role of the
      esophageal microbiome in disease pathogenesis, as well as methods for microbiome
      alteration, may help elucidate future targets for disease modifying therapies, or
      minimally invasive screening tools in patients at high risk for development of
      various esophageal conditions.

PMID- 29350340
TI  - POEM in the Treatment of Esophageal Disorders.
AB  - OPINION STATEMENT: PURPOSE OF THE REVIEW: Peroral endoscopic myotomy (POEM) is a
      novel minimally invasive technique that has emerged as the preferred option for
      the treatment of achalasia and spastic esophageal disorders (SED) at many centers
      around the world. In this article, we review and summarize the recent literature
      on POEM in patients with achalasia and SED. The current article is largely
      focused on the new developments and findings, extended applications, and long
      term outcomes of POEM in patients with achalasia and SED. RECENT FINDINGS: POEM
      is a safe and effective therapy for patients with achalasia and SED. POEM is
      comparable to Heller myotomy (HM) in terms of safety, efficacy, and
      complications, including gastroesophageal reflux disease (GERD). Outcomes of POEM
      are excellent even in patients who had prior failed therapies for achalasia,
      including failed HM and prior POEM. Recent data also suggest the efficacy and
      safety of POEM in both pediatric and geriatric patients. GERD after POEM is
      common, and the majority of patients are asymptomatic. The management, goals of
      therapy, and long-term outcomes of GERD after POEM are unclear. Objective testing
      for all patients is recommended. POEM is a validated treatment for all patients
      with achalasia and SED. Candidates should be carefully selected and appropriately
      counseled on expected outcomes and the need for long-term surveillance.

PMID- 29350341
TI  - Health, priority to the worse off, and time.
AB  - It is a common view that benefits to the worse off should be given priority when
      health benefits are distributed. This paper addresses how to understand who is
      worse off in this context when individuals are differently well off at different
      times. The paper argues that the view that this judgment about who is worse off
      should be based solely on how well off individuals are when their complete lives
      are considered (i.e. 'the complete lives view') is implausible in this context.
      Instead, it is argued that a pluralistic stance toward this issue should be
      accepted. This pluralistic stance recognizes that also the view that only focuses
      on how well off individuals are now and in the future (i.e. 'the forward-looking
      view') is relevant. The argument is based on appeals to intuitive judgments
      concerning who is worse off in different cases and reference to various
      underlying reasons why priority to benefits to the worse off is justified.

PMID- 29350342
TI  - Mesenchymal stromal cells of the bone marrow and natural killer cells: cell
      interactions and cross modulation.
AB  - Bone marrow-derived mesenchymal stromal cells (BM-MSCs) are multipotent
      progenitor cells that have shown promise for several different therapeutic
      applications. As they are able to modulate the function of several types of
      immune cells, BM-MSCs are highly important in the field of cell-based
      immunotherapy. Understanding BM-MSC-natural killer (NK) cell interactions is
      crucial for improving their therapeutic efficiency. Here, we observed that the
      type of NK cell-activating cytokine (e.g., IL-2, IL-12, IL-15 and IL-21) strongly
      influenced the outcomes of their interactions with BM-MSCs. The expression
      patterns of the ligands (CD112, CD155, ULPB-3) and receptors (LAIR, NCR)
      mediating the cross-talk between BM-MSCs and NK cells were critically modulated
      following co-culture. BM-MSCs partially impaired NK cell proliferation but up
      regulated their secretion of IFN-gamma and TNF-alpha. As they are cytotoxic,
      activated NK cells induced the killing of BM-MSCs. Indeed, BM-MSCs triggered the
      degranulation of NK cells and increased their release of perforin and granzymes.
      Interestingly, activated NK cells induced ROS generation within BM-MSCs that
      caused their decreased viability and reduced expression of serpin B9.
      Collectively, our observations reveal that BM-MSC-NK cell interactions may impact
      the immunobiology of both cell types. The therapeutic potential of BM-MSCs will
      be significantly improved once these issues are well characterized.

PMID- 29350343
TI  - Syringic acid, a phenolic acid, promotes osteoblast differentiation by
      stimulation of Runx2 expression and targeting of Smad7 by miR-21 in mouse
      mesenchymal stem cells.
AB  - Syringic acid (SA), a phenolic acid, has been used in Chinese and Indian medicine
      for treating diabetes but its role in osteogenesis has not yet been investigated.
      In the present study, at the molecular and cellular levels, we evaluated the
      effects of SA on osteoblast differentiation. At the cellular level, there was
      increased alkaline phosphatase (ALP) activity and calcium deposition by SA
      treatment in mouse mesenchymal stem cells (mMSCs). At the molecular level, SA
      treatment of these cells stimulated expression of Runx2, a bone transcription
      factor, and of osteoblast differentiation marker genes such as ALP, type I
      collagen, and osteocalcin. It is known that Smad7 is an antagonist of TGF
      beta/Smad signaling and is a negative regulator of Runx2. microRNAs (miRNAs) play
      a key role in the regulation of osteogenesis genes at the post-transcriptional
      level and studies have reported that Smad7 is one of the target genes of miR-21.
      We found that there was down regulation of Smad7 and up regulation of miR-21 in
      SA-treated mMSCs. We further identified that the 3'-untranslated region (UTR) of
      Smad7 was directly targeted by miR-21 in these cells. Thus, our results suggested
      that SA promotes osteoblast differentiation via increased expression of Runx2 by
      miR-21-mediated down regulation of Smad7. Hence, SA may have potential in
      orthopedic applications.

PMID- 29350344
TI  - The relationship between exercise dose and health-related quality of life with a
      phase III cardiac rehabilitation program.
AB  - PURPOSE: To quantify the relationship between the change in exercise dose and
      health-related quality of life (HRQoL) in a cohort of patients participating in a
      community-based phase-3 cardiac rehabilitation (CR) program. METHODS: A
      retrospective, pre-experimental (no control group) design of 58 participants that
      completed a phase-3, 12-week exercise-based CR program was used to test the
      current hypothesis. Self-reported HRQoL (36-Item Short Form Health Survey Version
      2, SF-36v2) was assessed prior and after completing the CR program. The change in
      exercise dose was estimated from the assigned training load in weeks 1 and 12 of
      the CR program. A series of regression models were fitted to ascertain the
      relationship between the change in exercise dose and changes in the SF-36v2.
      RESULTS: There was a strong quadratic trend between the change in exercise dose
      and the mean change in SF-36 Mental and Physical Health Summary Scores. Analysis
      of covariance showed that the mean changes in the SF-36 Summary Scores
      statistically fluctuate across quartiles of exercise dose. The data show that
      there is a threshold amount of increase in exercise (Q2; 350-510 kcal week- 1)
      needed to HRQoL and that greater amounts of exercise dose (Q3; 511-687 and Q4 >=
      688 kcal week- 1) did not improve HRQoL further. CONCLUSIONS: The current
      findings suggest that physical and mental health-related quality of life are
      improved with a phase-3 CR program. The dose-response relationship observed
      indicates that a threshold exercise dose is required to improve HRQoL, and that
      larger doses of exercise do not confer further improvements in HRQoL.

PMID- 29350345
TI  - Measurement invariance and general population reference values of the PROMIS
      Profile 29 in the UK, France, and Germany.
AB  - PURPOSE: Comparability of patient-reported outcome measures over different
      languages is essential to allow cross-national research. We investigate the
      comparability of the PROMIS Profile 29, a generic health-related quality of life
      measure, in general population samples in the UK, France, and Germany and present
      general population reference values. METHODS: A web-based survey was
      simultaneously conducted in the UK (n = 1509), France (1501), and Germany (1502).
      Along with the PROMIS Profile 29, we collected sociodemographic information as
      well as the EQ-5D. We tested measurement invariance by means of multigroup
      confirmatory factor analysis (CFA). Differences in the health-related quality of
      life between countries were modeled by linear regression analysis. We present
      general population reference data for the included PROMIS domains utilizing
      plausible value imputation and quantile regression. RESULTS: Multigroup CFA of
      the PROMIS Profile 29 showed that factor means are insensitive to potential
      measurement bias except in one item. We observed significant differences in
      patient-reported health between countries, which could be partially explained by
      the differences in overall ratings of health. The physical function and pain
      interference scales showed considerable floor effects in the normal population in
      all countries. CONCLUSIONS: Scores derived from the PROMIS Profile 29 are largely
      comparable across the UK, France, and Germany. Due to the use of plausible value
      imputation, the presented general population reference values can be compared to
      data collected with other PROMIS short forms or computer-adaptive tests.

PMID- 29350346
TI  - Chemical Characterization of Young Virgin Queens and Mated Egg-Laying Queens in
      the Ant Cataglyphis cursor: Random Forest Classification Analysis for
      Multivariate Datasets.
AB  - Social insects are well known for their extremely rich chemical communication,
      yet their sex pheromones remain poorly studied. In the thermophilic and
      thelytokous ant, Cataglyphis cursor, we analyzed the cuticular hydrocarbon
      profiles and Dufour's gland contents of queens of different age and reproductive
      status (sexually immature gynes, sexually mature gynes, mated and egg-laying
      queens) and of workers. Random forest classification analyses showed that the
      four groups of individuals were well separated for both chemical sources, except
      mature gynes that clustered with queens for cuticular hydrocarbons and with
      immature gynes for Dufour's gland secretions. Analyses carried out with two
      groups of females only allowed identification of candidate chemicals for queen
      signal and for sexual attractant. In particular, gynes produced more undecane in
      the Dufour's gland. This chemical is both the sex pheromone and the alarm
      pheromone of the ant Formica lugubris. It may therefore act as sex pheromone in
      C. cursor, and/or be involved in the restoration of monogyny that occurs rapidly
      following colony fission. Indeed, new colonies often start with several gynes and
      all but one are rapidly culled by workers, and this process likely involves
      chemical signals between gynes and workers. These findings open novel
      opportunities for experimental studies of inclusive mate choice and queen choice
      in C. cursor.

PMID- 29350347
TI  - Low birth weight is a conditioning factor for podocyte alteration and steroid
      dependance in children with nephrotic syndrome.
AB  - BACKGROUND: Low birth weight (LBW) is associated with reduced nephron endowment.
      Clinical-pathologic features of post adaptive focal segmental glomerulosclerosis
      (FSGS) have been observed in subjects with prematurity and very LBW. METHODS: We
      aimed to investigate the correlation between LBW and outcome in a cohort of 89
      children with idiopathic nephrotic syndrome (NS) (2-12 years-old at onset,
      followed for > 3 years), of whom 21 with LBW (birth weight < 10th percentile for
      gestational age, gender, ethnicity, and maternal parity or birth weight < 2500
      g). RESULTS: Children with NS and LBW were found to have FSGS more frequently
      than children with normal birth weight (NBW) [8/21 = 38% vs. 4/68 = 6%; odds
      ratio, OR 7.754 (95% confidence interval, CI 2.184-27.525); chi2 = 9.817; p <
      0.003]. Children with LBW and cortico-sensitive NS had a greater risk of cortico
      dependence (CD) than those with NBW [10/13 = 76.9% vs. 28/63 = 44.4%, OR 4.744
      (1.188-18.936); chi2 = 4.158; p < 0.05]. Moreover, children with LBW and CDNS
      needed a greater dose of immunosuppressive drugs than those with NBW [OR 4 (1.153
      13.877); chi2 = 3.842; p = 0.05]. CONCLUSIONS: LBW children developing NS had
      higher risk of FSGS and CD, and needed heavier immunosuppressive therapy than
      those with NBW. These data might suggest a conditioning role for hemodynamic and
      podocyte changes due to reduced nephron mass in LBW.

PMID- 29350348
TI  - SNF472, a novel inhibitor of vascular calcification, could be administered during
      hemodialysis to attain potentially therapeutic phytate levels.
AB  - BACKGROUND: Cardiovascular calcification (CVC) is a major concern in hemodialysis
      (HD) and the loss of endogenous modulators of calcification seems involved in the
      process. Phytate is an endogenous crystallization inhibitor and its low molecular
      mass and high water solubility make it potentially dialyzable. SNF472 (the
      hexasodium salt of phytate) is being developed for the treatment of calciphylaxis
      and CVC in HD patients. We aimed to verify if phytate is lost during dialysis,
      and evaluate SNF472's behaviour during dialysis. METHODS: Dialyzability was
      assessed in vitro using online-hemodiafiltration and high-flux HD systems in
      blood and saline. SNF472 was infused for 20 min and quantified at different time
      points. RESULTS: Phytate completely dialyzed in 1 h at low concentrations (10
      mg/l) but not when added at 30 or 66.67 mg/l SNF472. In bypass conditions,
      calcium was slightly chelated during SNF472 infusion but when the system was
      switched to dialysis mode the calcium in the bath compensated this chelation.
      CONCLUSION: Phytate dialyses with a low clearance. The administration of SNF472
      as an exogenous source of phytate allows to attain supra-physiological levels
      required for its potential therapeutic properties. As SNF472 is infused during
      the whole dialysis session, the low clearance would not affect the drug's
      systemic exposure.

PMID- 29350349
TI  - Discovery of the first macrolide antibiotic binding protein in Mycobacterium
      tuberculosis: a new antibiotic resistance drug target.

PMID- 29350350
TI  - Biochemical changes and clinical outcomes in 34 patients with classic
      galactosemia.
AB  - Impaired activity of galactose-1-phosphate uridyltransferase (GALT) causes
      galactosemia, an autosomal recessive disorder of galactose metabolism. Early
      initiation of a galactose-restricted diet can prevent or resolve neonatal
      complications. Despite therapy, patients often experience long-term complications
      including speech impairment, learning disabilities, and premature ovarian
      insufficiency in females. This study evaluates clinical outcomes in 34
      galactosemia patients with markedly reduced GALT activity and compares outcomes
      between patients with different levels of mean galactose-1-phosphate in red blood
      cells (GAL1P) using logistic regression: group 1 (n = 13) GAL1P <=1.7 mg/dL vs.
      group 2 (n = 21) GAL1P >= 2 mg/dL. Acute symptoms at birth were comparable
      between groups (p = 0.30) with approximately 50% of patients presenting with
      jaundice, liver failure, and failure-to-thrive. However, group 2 patients had
      significantly higher prevalence of negative long-term outcomes compared to group
      1 patients (p = 0.01). Only one of 11 patients >3 yo in group 1 developed
      neurological and severe behavioral problems of unclear etiology. In contrast, 17
      of 20 patients >3 yo in group 2 presented with one or more long-term
      complications associated with galactosemia. The majority of females >=15 yo in
      this group also had impaired ovarian function with markedly reduced levels of
      anti-Mullerian hormone. These findings suggest that galactosemia patients with
      higher GAL1P levels are more likely to have negative long-term outcome.
      Therefore, evaluation of GAL1P levels on a galactose-restricted diet might be
      helpful in providing a prognosis for galactosemia patients with rare or novel
      genotypes whose clinical presentations are not well known.

PMID- 29350352
TI  - The Problem Is Not Professional Publishing, But the Publish-or-Perish Culture.
AB  - The publication of scientific papers has become increasingly problematic in the
      last decades. Even if we agree that a renewed model is needed for peer-reviewed
      scientific publication, we think the problem does not essentially lie in
      professional publishing-with economic incentives-but in the publish-or-perish
      culture that dominates the lives of researchers and academics.

PMID- 29350351
TI  - Convection-enhanced delivery of cetuximab conjugated iron-oxide nanoparticles for
      treatment of spontaneous canine intracranial gliomas.
AB  - Cetuximab conjugated iron-oxide nanoparticles (cetuximab-IONPs) have shown both
      in-vitro and in-vivo anti-tumor efficacy against gliomas. The purpose of this
      pilot study was to evaluate the safety and potential efficacy of cetuximab-IONPs
      for treatment of spontaneously occurring intracranial gliomas in canines after
      convection-enhanced delivery (CED). The use of CED allowed for direct infusion of
      the cetuximab-IONPs both intratumorally and peritumorally avoiding the blood
      brain barrier (BBB) and limiting systemic effects. A total of eight dogs
      participated in the study and only two developed mild post-operative
      complications, which resolved with medical therapy. All canines underwent a
      single CED treatment of the cetuximab-IONPs over 3 days and did not receive any
      further adjuvant treatments. Volumetric analysis showed a median reduction in
      tumor size of 54.9% by MRI at 1-month (4-6 weeks) follow-up. Five dogs were
      euthanized due to recurrence of neurological signs other than seizures, two due
      to recurrent seizures, and one dog died in his sleep. Median survival time after
      surgery was 248 days (mean 367 days).

PMID- 29350353
TI  - Retraction and Research Integrity Education in China.
AB  - This article draws the attention of research managers and policy makers to the
      issue that to become a science power curtailing misconduct is the daunting
      challenge that emerging countries simply cannot ignore. Systematic and
      orchestrated efforts are needed to foster and institutionalize research integrity
      education among all stakeholders.

PMID- 29350354
TI  - Magnetic, geochemical characterization and health risk assessment of road dust in
      Xuanwei and Fuyuan, China.
AB  - As an accumulation of solid organic and inorganic pollutant particles on outdoor
      ground surfaces, road dust is an important carrier of heavy metal contaminants
      and can be a valuable medium for characterizing urban environmental quality.
      Because the dusts can be an important source of atmospheric particles and take
      impact on human health, the aim of this study described in detail the
      mineralogical characteristics, morphology, and heavy metal content of road dust
      from Xuanwei and Fuyuan, locations with high lung cancer incidence. Our results
      show that the average concentrations of heavy metals in road dust were higher
      than their background values. Higher concentrations of heavy metals were found in
      the magnetic fractions (MFs) than in the non-magnetic fractions (NMFs). Magnetic
      measurements revealed high magnetic susceptibility values in the road dust
      samples, and the dominant magnetic carrier was magnetite. The magnetic grains
      were predominantly pseudo-single domain, multi-domain, and coarse-grained stable
      single domains (coarse SSD) in size. SEM/XRD analysis identified two groups of
      magnetic particles: spherules and angular/aggregate particles. Hazard index (HI)
      values for adults exposure to road dust samples, including MF, Bulk, and NMF, in
      both areas were lower or close to safe levels, while HI values for childhood
      exposure to magnetic fractions in both areas were very close or higher than safe
      levels. Cancer risks from road dust exposure in both areas were in the acceptable
      value range.

PMID- 29350355
TI  - The biosorption of cadmium and cobalt and iron ions by yeast Cryptococcus
      humicola at nitrogen starvation.
AB  - Yeasts Cryptococcus humicola accumulated cadmium, cobalt, and iron (~ 50, 17, and
      4% of the content in the medium, respectively) from the medium containing
      glucose, phosphate, and 2 mmol/L of metal salts. The effects of metal absorption
      on the levels of orthophosphate (Pi) and inorganic polyphosphate (polyP) varied
      for the metals under study. The levels of Pi and polyP increased in the case of
      cadmium and cobalt, respectively. In the case of iron, no changes in the levels
      of Pi and polyP were observed. Multiple DAPI-stained polyP inclusions were
      observed in the cytoplasm of cadmium-containing cells. The intensity of DAPI
      staining of the cell wall especially increased in case of cobalt and iron
      accumulation.

PMID- 29350359
TI  - A Tribute to Dr. Shiro Miwa.

PMID- 29350358
TI  - Streptomyces AcH 505 triggers production of a salicylic acid analogue in the
      fungal pathogen Heterobasidion abietinum that enhances infection of Norway spruce
      seedlings.
AB  - The necrotrophic fungus Heterobasidion spp. is the causal agent of 'annosum root
      rot' of Norway spruce. In the presence of the rhizosphere bacterium Streptomyces
      AcH 505, enhanced colonization of Norway spruce roots with Heterobasidion
      abietinum 331 has previously been observed. By analyzing dual cultures of H.
      abietinum 331 and Streptomyces AcH 505 with HPLC, a fungal metabolite was
      identified that was increased in the presence of Streptomyces AcH 505. Likewise,
      challenge of H. abietum 331 with common antifungals produced by soil
      streptomycetes rendered the same effect. The structure of the compound, 5
      formylsalicylic acid (5-FSA), was elucidated by HPLC-HR-ESI-Orbitrap-mass
      spectrometry and NMR spectroscopy. Based on in vivo measurements of maximum
      photosystem II efficiency of Norway spruce seedlings, 5-FSA did not influence
      plant vitality. However, when challenged with H. abietinum 331, ergosterol
      amounts in infected roots increased significantly for 5-FSA pre-treated
      seedlings. The severity of the infection was comparable to that observed in the
      presence of Streptomyces AcH 505. 5-FSA is a structural analogue of salicylic
      acid, an important signalling molecule active in plant defence. Thus, the
      expression of two defence-response related marker genes (PR1, Hel) was analysed
      in 5-FSA treated Arabidopsis thaliana seedlings by Northern blot analysis. The
      transcription of both marker genes was altered, indicating that 5-FSA is
      perceived by Arabidopsis in a similar manner to salicylic acid and is able to
      interfere with Arabidopsis defence signalling. The role of 5-FSA as a potential
      virulence factor of H. abietinum 331 in the presence of Streptomyces AcH 505 is
      discussed.

PMID- 29350360
TI  - In Memoriam Professor Shiro Miwa.

PMID- 29350361
TI  - Evaluation of tourniquet application in a simulated tactical environment.
AB  - BACKGROUND: Application of a tourniquet in a tactical environment is implemented
      in two ways: the so-called self-aid, which is the application of a tourniquet by
      the injured, and the so-called buddy aid, which is the application of a
      tourniquet by the person provide aid. This study aimed to test the quality of
      tourniquet use in a simulated situation, close quarter battle. METHODS: The study
      involved 24 injured operators and 72 operators in the whole simulation, implying
      12 sections of six individuals. To validate the application of tourniquets, the
      recommendations of the Committee of Tactical Combat Care of the Injured were
      used, and ultrasound with Doppler function was employed to assess the hemodynamic
      effect of applying tourniquets. RESULTS: Native flow was observed in 15
      operators; in three people, a trace flow was noticed, whereas in six people, a
      full flow was observed. No significant difference was found between the qualities
      of tourniquet application by the operators themselves compared with those of
      tourniquet application by another person. The median distance of tourniquet
      application from the armpit was 9.5 cm for self-aid and buddy aid. In 16
      participants the outer arrangement of tourniquets was observed, and in only eight
      participants tourniquets were correctly located on the internal part of the arm.
      In 18 participants, tourniquets were not correctly prepared for use in the
      tactical environment, whereas in only six participants, they were correctly
      prepared. Most operators with a negative ultrasound flow revealed negative distal
      observed pulse (DOP). Positive DOP occurred in the majority of operators with
      full ultrasound flow. CONCLUSION: The application of tourniquets poses a
      challenge even in case of specialized units; therefore, there is a need to
      provide regular training for implementing that procedure.

PMID- 29350362
TI  - Which common test should be used to assess spleen autotransplant effect?
AB  - BACKGROUND: Historically, total splenectomy was the only choice of treatment for
      traumatic splenic injuries. However, nonoperative management and spleen
      preserving surgical techniques are preferred in modern medicine. In some
      situations in which the surgeon has to perform splenectomy, spleen autotransplant
      may preserve the splenic function. Selecting the best method for evaluating the
      splenic autotransplant effect has been debated for several years. In this study,
      we compared three common tests in evaluating the implanted spleen function.
      METHODS: Participants included 10 patients who were candidates for laparotomy and
      splenectomy. After performing splenectomy, we implanted five pieces of the spleen
      in the greater omentum of each patient. After 3 months, the implanted spleen
      function was evaluated by nuclear red blood cell (RBC) scan, serum immunoglobulin
      (Ig) M level, and presence of Howell-Jolly (HJ) bodies in the peripheral blood
      smear. RESULTS: All patients had normal peripheral blood smear. The IgM level was
      lower than normal in one patient, and scintigraphy did not demonstrate the
      transplanted spleen in another patient. CONCLUSION: All these tests may have
      comparable results, but because of availability and low cost of peripheral blood
      smear, which is also easily performed, it can be considered as the first option
      to evaluate the implanted spleen function.

PMID- 29350363
TI  - Is nighttime laparoscopic general surgery under general anesthesia safe?
AB  - BACKGROUND: Fatigue and sleep deprivation can affect rational decision-making and
      motor skills, which can decrease medical performance and quality of patient care.
      The aim of the present study was to investigate the association between times of
      the day when laparoscopic general surgery under general anesthesia was performed
      and their adverse outcomes. METHODS: All laparoscopic cholecystectomies and
      appendectomies performed at the emergency surgery department of a tertiary
      university hospital from 01. 01. 2016 to 12. 31. 2016 were included. Operation
      times were divided into three groups: 08.01-17.00 (G1: daytime), 17.01-23.00 (G2:
      early after-hours), and 23.01-08.00 (G3: nighttime). The files of the included
      patients were evaluated for intraoperative and postoperative surgery and
      anesthesia-related complications. RESULTS: We used multiple regression analyses
      of variance with the occurrence of intraoperative complications as a dependent
      variable and comorbidities, age, gender, body mass index (BMI), ASA score, and
      operation time group as independent variables. This revealed that nighttime
      operation (p<0.001; OR, 6.7; CI, 2.6-16.9) and older age (p=0.004; OR, 1.04; CI,
      1.01-1.08) were the risk factor for intraoperative complications. The same
      analysis was performed for determining a risk factor for postoperative
      complications, and none of the dependent variables were found to be associated
      with the occurrence of postoperative complications. CONCLUSION: Nighttime surgery
      and older patient age increased the risk of intraoperative complications without
      serious morbidity or mortality, but no association was observed between the
      independent variables and the occurrence of postoperative complications.

PMID- 29350364
TI  - A retrospective analysis of 2713 hospitalized burn patients in a burns center in
      Turkey.
AB  - BACKGROUND: Burn trauma is a significant health problem that has physical,
      psychological, and economic repercussions on affected patients. The aim of this
      study was to present epidemiological and demographic characteristics of patients
      treated over an 8-year period at a reference burn treatment center located in the
      northeast of Turkey and serving a population of approximately four million
      people. METHODS: Each patient's medical record was reviewed, and demographic
      features, source of burns, place of residence, total body surface area (TBSA),
      surgical treatment, duration of hospital stay, and mortality rates were analyzed.
      RESULTS: The most frequent cause of burn was scalding from hot liquids (2013
      cases, 74.2%). Freeze burn was observed in 16 (0.6%) cases due to climatic
      conditions of the region where our burn center is located. Grouping based on TBSA
      revealed that 88.7% patients had TBSA of 0%-15%, 8% patients had TBSA of 15%-30%,
      and 3.3% patients had TBSA >= %30.The most common microorganism was Pseudomonas
      aeruginosa. A total of 24 patients (0.9%; 8 males, 16 females) died, including 7
      children and 17 adults. CONCLUSION: Removal of tandirs and replacement with high
      ovens, restriction of cheese and butter production under primitive circumstances,
      encouraging cheese and butter production via dairy farm systems, and raising
      people's awareness through training programs could greatly reduce the number of
      the burn accidents occurring in this region.

PMID- 29350365
TI  - Characteristics of pediatric and adult cases with open globe injury and factors
      affecting visual outcomes: A retrospective analysis of 294 cases from Turkey.
AB  - BACKGROUND: This study aimed to evaluate 1-year follow-up results of cases that
      were diagnosed with open globe injury (OGI), to compare trauma-related
      characteristics between pediatric and adult cases, and to determine risk factors
      for a poor final visual acuity. METHODS: This study enrolled 294 cases that met
      the OGI definition and were followed up for at least 1 year. Demographic and
      clinical features regarding ocular trauma were recorded. The cases were divided
      into two groups according to age: pediatric (<=16 years) and adult (>16 years)
      groups. RESULTS: Children were exposed to accidents that led to OGI mostly at
      home, whereas adults were exposed to such accidents mostly in the office.
      Penetrating injuries were more common in children than in adults, and injuries
      most commonly occurred owing to spiky objects. Zone I injuries were most frequent
      in both children and adults. The frequency of high-grade injuries increased with
      age. Foreign body injuries and multiple surgeries were more common in adults than
      in children. There was no difference between the two age groups based on ocular
      trauma score (OTS) and visual acuity. OTS predicted the need for multiple
      surgeries. In the adult group, age, multiple surgeries, and initial visual acuity
      were significant risk factors for the final visual acuity that was achieved.
      CONCLUSION: OGI causes and risk factors for poor final visual outcomes differ in
      adults and children. The knowledge of these differences is crucial for taking
      adequate preventive measures and decreasing morbidity.

PMID- 29350366
TI  - Health results of a coup attempt: evaluation of all patients admitted to
      hospitals in Istanbul due to injuries sustained during the July 15, 2016 coup
      attempt.
AB  - BACKGROUND: A coup attempt against the government took place in Turkey on July
      15, 2016. This attempt caused serious injuries and deaths in the country. In this
      study, the data of patients referred to all hospitals in Istanbul during the
      attempt were evaluated, and differences between natural disasters, other
      terrorist actions, and coup attempts were analyzed. METHODS: In total, 1104
      patients were injured in the abovementioned coup attempt. In this study, the
      demographic and health information of 882 coup victims who were admitted to all
      hospitals (state and private) in Istanbul on July 15 and 16, 2016 and registered
      at the Crisis Center of Istanbul Provincial Health Directorate was analyzed.
      RESULTS: Of the 882 patients evaluated, 97.27% were male and 2.73% were female.
      The mean age of the patients was 34.12 years. Most (82.43%) patients were
      admitted to state hospitals, and 17.57% were admitted to private hospitals. The
      total mortality rate due to the abovementioned coup attempt was 10.4% (9.76% in
      state hospitals and 13.54% in private hospitals). Of the 882 patients evaluated,
      65.07% had gunshot injuries, 11.11% had been assaulted, 7.70% had experienced
      tank/motor vehicle accidents, 5.44% had other penetrating injuries, 5.32% had
      soft-tissue trauma, 2.83% had experienced falls (including falls from heights),
      0.33% had psychiatric disorders, and 2.15% were admitted for other reasons.
      CONCLUSION: The patterns of injury and mortality resulting from the July 15, 2016
      coup attempt differed from those resulting from natural disasters and terrorist
      acts and were similar to those encountered during wars: the victims were
      predominantly male, similar to those in wars. Following a coup attempt, an
      increase in the number of patients with post-traumatic stress disorder can be
      expected. Further studies focusing on the incidence of this disorder due to the
      abovementioned coup attempt in Turkey are needed. Hospital disaster plans need to
      include information and plans related to terrorist acts, such as coup attempts.

PMID- 29350367
TI  - Posterior interosseous flap versus reverse adipofascial radial forearm flap for
      soft tissue reconstruction of dorsal hand defects.
AB  - BACKGROUND: Our objective was to compare the outcomes of dorsal hand defect
      reconstruction using a posterior interosseous artery flap (PIAF) and a reverse
      adipofascial radial forearm flap (RARFF). METHODS: From 2008 to 2013, 23 patients
      who underwent hand soft tissue defect reconstruction with PIAF (11 patients) and
      RARFF (12 patients) were included in this retrospective study. Reconstruction
      methods were compared in terms of functionality with disability of the arm,
      shoulder, and hand (DASH) score and range of motion (ROM) and aesthetically with
      scar assessment. Operation times, length of hospital stay, and donor site
      problems were compared. RESULTS: We found no statistically significant
      differences between PIAF and RARFF in terms of ROM, DASH score, and length of
      hospital stay. Statistically significant differences were found in operation
      time, scar assessment, and donor site problems between PIAF and RARFF patients.
      CONCLUSION: RARFF showed better results than PIAF in dorsal hand defects, but in
      RARFF, the major arteries of the hand are sacrificed.

PMID- 29350368
TI  - Clinical features, diagnosis, and treatment of traumatic pulmonary pseudocysts.
AB  - BACKGROUND: Traumatic pulmonary pseudocysts (TPP) are rare complications of blunt
      chest trauma. The aim of this study is to increase the understanding of this rare
      entity with imaging and clinical parameters for preventing complications and
      determining the correct treatment approach by observing 15 cases. METHODS: We
      retrospectively reviewed the medical data and thoracic computed tomography scans
      of 185 patients who underwent examinations in our department after chest trauma
      between July 2014 and December 2015. RESULTS: Fifteen patients had TPPs, and
      their clinical features and imaging findings were evaluated. Their average age
      was 26.33 (range, 1-89) years. The cause of TPP was traffic accident in 13
      patients and falling from a height in two. Tube thoracostomy was required in five
      patients. None of the patients required thoracotomy, and 66% of them recovered
      without any complications. Five patients died because of serious concomitant
      injuries. CONCLUSION: Sudden shearing force across the pulmonary parenchyma
      results in an area of pulmonary contusion and airtransfer from the airway to the
      contused area, which in turn leads to pneumatocele formation. Conservative
      treatment is recommended for these patients, but complications can occur because
      of cyst rupture. Patients should be closely monitored and be made aware of the
      risk of life-threatening complications.

PMID- 29350369
TI  - Analyses of combat-related injuries to the maxillofacial and cervical regions and
      experiences in an operational field hospital.
AB  - BACKGROUND: With the changing conditions of war, maxillofacial injuries are
      observed more frequently. Particularly in urban areas, high-energy explosive
      devices (HEEDs), such as improvised explosive devices, are often used alongside
      long-barreled weapons (LBWs). It is important to use trauma scoring systems and a
      multidisciplinary approach for medically and accurately responding to the trauma
      patient in a timely manner. This study aimed to compare the Military Combat
      Injury Scale (MCIS) and Military Functional Incapacity Scale (MFIS) between
      injuries sustained by LBWs or HEEDs and to share experiences of an operational
      field hospital. METHODS: Medical data of 84 patients admitted to an operational
      field hospital with maxillofacial and cervical injuries sustained by LBWs and
      HEEDs between July 27, 2015, and July 22, 2016 were reviewed. MCIS and MFIS
      scores were calculated for all patients; records of the qualifying patients were
      studied for the Glasgow Coma Scale (GCS) scores and injury sites. The patients
      were divided into two groups according to the device/weapon causing the injury:
      injuries sustained by LBWs in group I and those sustained by HEEDs in group II.
      RESULTS: All patients were males, with a mean age of 28.75 (range 20-58) years.
      The average GCS score was 13.4, but it was lower than 15 in 16 (19%) of the
      patients. There was no statistically significant difference in MCIS scores
      between the LBW and HEED groups (p=0.206). In addition, there was no
      statistically significant difference in MFIS scores between the LBW and HEED
      groups (p=0.238). CONCLUSION: Maxillofacial and cervical region injuries are
      increasing in modern conflicts that are usually located in urban areas. Injuries
      sustained by HEEDs as well as those sustained by LBWs in the maxillofacial area
      are morbid and mortal. Rapid and comprehensive intervention is life-saving and
      helping the patient to further trauma treatment.

PMID- 29350370
TI  - Operative and non-operative management of children with abdominal gunshot
      injuries.
AB  - BACKGROUND: Non-operative management (NOM) is a standard treatment method for
      solid organ injuries worldwide. There is no consensus on the management of
      gunshot wounds (GSW) because of the higher frequency of hollow viscus injuries
      (HVI) and the unpredictable depth of tissue damage produced by kinetic energy
      transfer during retardation of the bullet. Here we aimed to reevaluate
      indications for surgery and NOM based on our pediatric patients with abdominal
      GSW. METHODS: We performed a retrospective analysis of patients evaluated and
      treated for abdominal GSW at University of Dicle between January 2010 and October
      2016. Patients with hemodynamic instability, signs of peritonitis on serial
      abdominal examination, and free air in the abdomen underwent laparotomy; these
      were included in group I (n=17). Patients managed non-operatively were included
      in group II (n=13). RESULTS: Our statistical analysis showed significantly lower
      Hb levels and systolic blood pressure levels (p<0.001) and higher pulse rate,
      higher mean injury severity score, and longer length of stay at intensive care
      unit in patients in group I than in those in group II (p<0.001). We further
      detected colon perforation (n=10) and small bowel perforation (n=7) in patients
      in group I; liver laceration (n=4), splenic injury (n=1), and renal injury (n=3)
      but no solid organ injury or HVI (n=5) were detected in patients in group II.
      CONCLUSION: The major drawback of NOM is the difficulty in diagnosing HVI in
      abdominal GSW, which may delay treatment. We suggest that patients with solid
      organ damage who are hemodynamically stable and exhibit no signs of peritonitis
      upon serial abdominal exam may be treated with NOM.

PMID- 29350371
TI  - Fundus-first technique and partial cholecystectomy for difficult laparoscopic
      cholecystectomies.
AB  - BACKGROUND: This study aims to evaluate the impact of conversion from retrograde
      dissection to fundus-first technique (FF) or laparoscopic partial cholecystectomy
      (LPC) on complication rates, operation time, and duration of hospitalization.
      METHODS: The medical records of 210 consecutive patients who underwent
      laparoscopic cholecystectomy between January 2010 and December 2014 were
      retrospectively evaluated. All laparoscopic cholecystectomies were initiated with
      retrograde dissection (RD). In cases of difficulty in dissection of critical view
      of safety , the operation strategy was first converted to FF and then to LPC when
      FF was considered insufficient for safe cholecystectomy. RESULTS: Of the 210
      cases, LC was initiated and completed with RD in 197 cases. FF was implemented in
      13 cases due to difficulties in dissection. In the FF group, laparoscopic total
      cholecystectomy was successfully accomplished in seven patients, and LPC was
      performed in the remaining six cases. Three postoperative complications occurred
      in the RD group and two in the LPC group. No major intraoperative complications
      or perioperative mortality occurred in any patients. CONCLUSION: In elective,
      noncomplicated cases, the safe posterior window (critical view of safety)
      principle should be implemented. However, in complicated cases where anatomic
      uncertainties are dominant, the performance of FF technique or LPC may decrease
      conversion rates to open surgery and contribute to accomplishing the laparoscopic
      intervention safely.

PMID- 29350372
TI  - Endoscopic diagnosis and treatment of biliary obstruction due to acute
      cholangitis and acute pancreatitis secondary to Fasciola hepatica infection.
AB  - In the differential diagnosis of biliary obstruction with unknown etiology,
      biliary fascioliasis should be considered in endemic and nonendemic regions.
      After diagnostic evaluation, endoscopic retrograde cholangiopancreatography
      (ERCP) was performed for etiological evaluation and/or treatment of biliary
      obstruction in five patients with a mean age of 55.8 years. Endoscopic
      sphincterotomy and cholangiogram revealed linear filling defects in the biliary
      system. Fasciola hepatica parasites were extracted using balloon and basket
      catheters in two and three patients, respectively. No morbidity or mortality was
      observed. F. hepatica infection should be considered as a differential diagnosis
      of biliary obstruction with unknown etiology in endemic and non-endemic regions.
      ERCP can be the standard diagnostic and/or therapeutic procedure in cases of
      biliary obstruction due to fascioliasis. Due to slippery and gel-like
      characteristics of the parasite, use of a basket catheter in semi-opened position
      may be required in case of unsuccessful extraction using a balloon catheter.

PMID- 29350373
TI  - Pediatric dural venous sinus thrombosis following closed head injury: an easily
      overlooked diagnosis with devastating consequences.
AB  - Dural venous sinus thrombosis (DVST) is an uncommon finding after traumatic brain
      injury. The diagnosis can often be initially missed, particularly if not
      associated with an overlying fracture. Pediatric DVST following closed head
      injury and without an overlying fracture is very rare, with only 20 cases
      reported in the literature to date. Here we present the case of a 19-month-old
      boy who presented with a history of trivial fall and an episode of fever. On
      presentation, the pediatric Glasgow Coma Scale (pGCS) score was E3V4M6, and
      initial brain computed tomography (CT) was normal. He was initially
      conservatively managed. However, subsequent CT, taken following an episode of
      seizure, revealed right tentorial subarachnoid hemorrhage and falx hematoma.
      Conservative management was continued till he started developing recurrent
      seizures with a decrease in pGCS scores. Repeat CT revealed sinus thrombosis that
      involved the posterior aspect of the superior sagittal sinus with a massive brain
      edema. The coagulation profile was normal, and no fracture overlying the sinus
      was observed. Although he underwent emergency bifrontal decompressive craniotomy,
      he did not recover. This study emphasizes on the importance of not missing the
      diagnosis of sinus thrombosis and the devastating consequences that can occur if
      it is overlooked.

PMID- 29350374
TI  - Extension of a coronary intramural hematoma after blunt chest trauma.
AB  - Coronary artery dissection and intramural hematoma after blunt chest trauma are
      rare, but life-threatening, complications. Coronary intramural hematoma extension
      is even rarer. A 31-year-old man was transferred to our hospital for worsening
      left chest pain during while he was admitted at a nearby hospital due to blunt
      chest trauma. Bedside echocardiography showed akinesis of the left ventricular
      apex and anterior wall as well as hypokinesis of the mid-to-basal anteroseptal
      wall and mid-to-basal lateral and posterior walls of the left ventricle. Computed
      tomography coronary angiography revealed intramural hematoma in the left main
      (LM) coronary and proximal left anterior descending (LAD) arteries. Percutaneous
      coronary intervention, with bare metal stent implantation from the LM coronary
      artery to the proximal LAD artery, was performed to treat the occlusion caused by
      the hematoma. After stenting, the hematoma that compressed the LM coronary artery
      shifted the left circumflex (LCX) artery, and the intramural hematoma developed
      and extended to the LCX artery. To resolve this occlusion, a drug-eluting stent
      was successfully implanted in the LCX artery. The patient was discharged without
      complications. At 2-month follow-up, he remained asymptomatic, with no recurrence
      of cardiovascular symptoms. Delayed chest pain after trauma should be suspected
      during coronary dissection, and on treatment, care must be taken to extend the
      hematoma.

PMID- 29350375
TI  - Neurological recovery after traumatic Cauda Equina syndrome due to glass
      fragments: An unusual case.
AB  - Penetrating spinal injuries with foreign bodies are exceedingly rare. To date,
      pathological problems due to glass fragments in the spinal canal have rarely been
      reported. In this report, the case presenting with a back laceration, leg pain,
      and leg weakness was found to have glass frag-ments in the spinal canal at the L2
      L3 level by lumbar computed tomography and magnetic resonance imaging. After L2
      total laminectomy and retrieval of the glass fragments, the dura was re-paired.
      The patient was discharged from the hospital after complete neurological
      recovery. In cases of spinal canal injuries due to foreign bodies, early
      operative decompression of the neural elements is the treatment of choice.
      Patients with Cauda Equina syndrome due to glass fragments have a good prognosis
      for functional recovery.

PMID- 29350376
TI  - An unexpected long-term complication of genital burn in a child: Secondary
      cryptorchidism.
AB  - Genital and perineal burns are rare and challenging injuries with serious long
      term complications. Involvement of the testes is a sign of severity. There is
      limited knowledge in the literature about the management of complications and
      testes involvement in genital and perineal burns. In this report, we present the
      case of an 8-year-old boy with secondary cryptorchidism due to burn contracture
      who was treated by increasing the scrotal volume by Z-plasties, skin graft, and
      orchidopexy.

PMID- 29350377
TI  - Melatonin exhibits supportive effects on oxidants and anastomotic healing during
      intestinal ischemia/reperfusion injury.
AB  - BACKGROUND: The aim of this study was to investigate the effects of melatonin on
      intestinal anastomosis after intestinal ischemia/ reperfusion injury (IRI).
      METHODS: Thirty Wistar albino rats of both sexes were divided into 3 groups:
      sham, control, and treatment. IRI was performed by clamping the superior
      mesenteric artery (SMA) for 30 minutes, followed by reperfusion. The sham rats
      received only manipulation of the SMA. Melatonin (10 mg/kg) was administered to
      the treatment group, and the control group was given a vehicle injection. Both
      the treatment group and the control group further underwent ileal resection of a
      1-cm segment and anastomosis. On the postoperative seventh day, the anastomotic
      burst pressure, hydroxyproline level, histological indices of wound healing, and
      oxidative parameters of catalase (CAT), superoxide dismutase (SOD), total
      glutathione (T-GSH), and glutathione peroxidase (GSH-Px) levels were measured. A
      one-way analysis of variance and chi-square test were used for the categorical
      data. RESULTS: Melatonin treatment led to a significantly higher burst pressure
      (p=0.027 and p<0.001, respectively). The 2 antioxidant enzymes, CAT and SOD, were
      at the highest level in the sham and melatonin groups and the lowest level in the
      control group (p=0.001 and p=0.002, respectively). Melatonin treatment resulted
      in a significantly higher level of both enzymes compared with the control group
      (p=0.026 and 0.003, respectively). The GSHpx and total GSH levels were slightly
      elevated in the treated rats, but the difference was not statistically
      significant (p=0.205 and 0.216, respectively). Fibroblast infiltration, capillary
      formation, and epithelialization were significantly better in the melatonin
      treated animals. The granulocyte and mononuclear infiltration scores were similar
      between all groups. CONCLUSION: It was concluded that melatonin had marked
      effects on intestinal anastomotic healing during intestinal IRI.

PMID- 29350378
TI  - EQ-5D studies in cardiovascular diseases in eight Central and Eastern European
      countries: a systematic review of the literature.
AB  - BACKGROUND: The measurement of health-related quality of life (HRQoL) by
      validated generic instruments, such as EQ-5D, has become an increasingly
      important tool for the assessment of health care in a wide range of diagnoses.
      AIM: We aimed to systematically review EQ-5D literature on cardiovascular
      diseases in eight Central and Eastern European (CEE) countries. METHODS: A
      structured literature search was conducted in MEDLINE, EMBASE, Web of Science,
      CINAHL, PsycINFO, Cochrane Library, and the EuroQol website up to November 2016.
      Original cardiovascular-related studies that reported EQ-5D results were
      included. RESULTS: Of the 36 papers, 17 reported EQ-5D index scores. Most studies
      were performed in Poland (n = 24, 67%). The most common diagnosis regarding the
      number of publications and population size was ischaemic heart disease (n = 13, N
      = 6394), followed by atrial fibrillation (n = 4, N = 1052). The average EQ-5D
      index scores ranged from 0.61 to 0.88 and from 0.66 to 0.95 for patients before
      and after cardiac procedure/surgery, respectively (including angioplasty,
      coronary artery bypass grafting, ablation, surgical correction of septal defects,
      transcatheter aortic valve implantation [TAVI]). In all studies baseline scores
      were lower than the repeated assessments after the procedure, with the most
      substantial improvement of 0.24 in high-risk elderly patients after TAVI. Studies
      which did not assess invasive treatment reported mean EQ-5D index scores ranging
      from 0.18 to 0.80. CONCLUSIONS: The number of cardiovascular-related studies
      reporting HRQoL using EQ-5D has consistently increased in CEE countries over the
      past decade and is outstanding compared with other clinical fields. The EQ-5D
      index and EQ VAS scores varied based on the disease severity, patient
      characteristics, and treatment protocol.

PMID- 29350379
TI  - Metabolic syndrome in HIV infected adults in Poland.
AB  - BACKGROUND: Metabolic syndrome (MS) is usually diagnosed based on the presence of
      abdominal obesity, elevated blood pres-sure (BP), elevated fasting plasma
      glucose, high serum triglycerides (TG), and low high-density lipoprotein (HDL)
      cholesterol levels. Whether HIV is associated with a higher prevalence of MS than
      in the general population remains unclear. AIM: The aim of the study was to
      determine the incidence of MS in the population of HIV-infected adults and its
      association with clinical, virological, and biochemical features. METHODS: Two
      hundred and seventy HIV-infected Caucasian adult patients were enrolled in the
      study and evaluated based on clinical records in the years 2013-2015. RESULTS:
      Metabolic syndrome was diagnosed in 60 of 270 (22%) patients, 47 (24%) males and
      13 (17%) females, mostly (72%) aged above 40 years. The percentage of patients
      with diagnosed MS in specific age groups in comparison to the general Polish
      population for females aged < 40 years was 7% vs. 4%, and males in the same age -
      18% vs. 9%, for females aged 40-59 years - 47% vs. 24.4%, and males - 33% vs.
      28.3%. Particular components of MS in the MS population were found as follows:
      body mass index > 30 kg/m2 in 29%, waist circumference exceeding 94 cm in men and
      80 cm in woman - 87.5%, TG >= 150 mg/dL - 82%, HDL cholesterol < 40/50 mg/dL
      (males/females) - 42%, systolic/diastolic BP >= 130 mmHg/>= 85 mmHg - 83%, and
      fasting glucose > 100 mg/dL - 42%. In stepwise multivariate logistic regression
      analysis, age (odds ratio [OR] 1.052, 95% con-fidence interval [CI] 1.018-1.088,
      p = 0.003) and nadir CD4 < 350 cells/mm3 (OR 3.576, 95% CI 1.035-12.355, p =
      0.04) were associated with MS. Patients with MS compared with those without this
      disorder had low, intermediate, high, and very high cardiovascular risk in 10%
      vs. 23%, 73% vs. 70%, 7% vs. 5%, and 10% vs. 2%, respectively (p = 0.006).
      CONCLUSIONS: Prevalence of MS in the HIV-infected population is higher than in
      the general Polish population. Age and low nadir CD4 were found to be associated
      with MS.

PMID- 29350380
TI  - Patients treated with bivalirudin are still at higher risk of stent thrombosis: a
      comprehensive meta-analysis of randomised clinical trials of bivalirudin and
      heparin for percutaneous coronary interventions.
AB  - BACKGROUND: Although the current practice guidelines recommend using both heparin
      and bivalirudin for percutaneous coronary interventions (PCI), the research data
      are ambiguous. AIM: The aim of the study was to compare the impact of bivalirudin
      and heparin on major clinical endpoints in PCI patients with particular emphasis
      on periprocedural stent thrombosis. METHODS: A total of 18 randomised clinical
      trials involving 41,752 subjects were included. The endpoints comprised: net
      adverse clinical event (NACE: death, myocardial infarction [MI], unscheduled
      revascularisation, major bleeding), major adverse cardiovascular event (MACE:
      death, MI, or stroke), and acute/subacute stent thrombosis (ST). A subanalysis
      for planned and provisional glycoprotein IIb/IIIa inhibitor (GPI) use with
      heparin was performed. Results were presented as risk ratios (RR) and 95%
      confidence intervals (CI). RESULTS: Bivalirudin significantly reduced NACE risk
      (RR 0.85, 95% CI 0.76-0.96) and increased the incidence of MI (RR 1.09, 95% CI
      1.01-1.18), ST (RR 1.50, 95% CI 1.13-1.99), and MACEs (RR 1.06, 95% CI 0.99
      1.13). Comparing to heparin with provisional or planned GPI use, there was higher
      risk of acute ST with bivalirudin (RR 2.14, 95% CI 1.01-4.56 and RR 5.53, 95% CI
      2.32-13.18, respectively). Comparing to heparin and provisional GPIs, bivalirudin
      failed to reduce NACEs and major bleeding. However, it decreased rates of NACEs
      (RR 0.81, 95% CI 0.69-0.96) and major bleeding (RR 0.64, 95% CI 0.48-0.85)
      compared with heparin and planned GPI use. CONCLUSIONS: The advantages of
      bivalirudin are undoubtedly related to GPI use in the heparin arms. Bivalirudin
      based regimens are more beneficial when compared with heparin and planned GPI use
      in terms of NACE and major bleedings; this was not observed when compared to
      heparin and provisional GPI use. Regardless of adjunctive GPI use, stent
      thrombosis episodes were significantly more common in bivalirudin-treated
      subjects. Therefore, the safety and economic issues may urge revision of this
      aspect of current clinical practice and guidelines.

PMID- 29350381
TI  - Macrophage migration inhibitory factor knockout attenuates endotoxin-induced
      cardiac dysfunction in mice.
AB  - BACKGROUND: Accumulated evidence suggests that macrophage migration inhibitory
      factor (MIF) plays a key role not only in acute and chronic inflammatory diseases
      but also in cardiovascular disease. The cardiac dysfunction is related to
      lipopolysac-charide (LPS) in sepsis. AIM: This study was designed to examine
      whether MIF mediates LPS-induced cardiac dysfunction and address the mechanisms.
      METHODS: Echocardiography, immunohistochemical analysis, cell shortening/re
      lengthening, and intracellular Ca2+ fluores-cence evaluation were performed in
      whole hearts and isolated cardiomyocytes from C57 and MIF knockout mice treated
      with or without LPS. Reactive oxygen species and protein carbonyl formation were
      measured. Activation of mitogen-activated protein kinases and endoplasmic
      reticulum stress markers were evaluated using Western blot analysis. Human
      umbilical vein endothelial cells (HUVECs) were transfected with lentiviruses
      carrying short hairpin RNA (shRNA) to inhibit MIF. RESULTS: Echocardiography
      revealed that cardiac function was impaired and macrophage infiltration was
      increased in LPS-treated C57 mice. Peak shortening and maximal velocity of
      shortening/re-lengthening were significantly reduced and the duration of re
      lengthening was prolonged in LPS-treated C57 mice. Reactive oxygen species and
      protein carbonyl levels were increased in LPS-treated C57 mice. These
      dysfunctional changes were attenuated in MIF knockout mice that were challenged
      with LPS. Western blot analysis revealed that activated p-JNK, p-ERK, and
      endoplasmic reticulum stress protein marker expression was decreased in LPS
      treated MIF knockout mice. p-ERK and p-JNK levels were knocked down in MIF shRNA
      transfected HUVECs. CONCLUSIONS: The data collectively suggest that MIF mediates
      LPS-induced cardiac dysfunction in murine cardiomyocytes, which was attenuated by
      MIF knockout, and the therapeutic option with regard to MIF may aid the
      management of cardiac dysfunction in sepsis.

PMID- 29350382
TI  - Risk factors for adverse outcomes of patients with acute coronary syndrome:
      single-centre experience with long-term follow-up of treated patients.
AB  - BACKGROUND: For patients experiencing an acute coronary syndrome (ACS), a crucial
      time to assess their prognosis and to plan management is at discharge from
      hospital. AIM: The aim of the study was to identify risk factors of mortality
      during post-discharge period following a hospitalisation for ACS. METHODS: We
      studied 672 consecutive ACS patients hospitalised and discharged alive between
      2002 and 2004. The analysis was done with respect to the type of ACS, i.e.
      unstable angina/non-ST-segment elevation myocardial infraction (UA/NSTEMI; n =
      255) vs. ST-segment elevation myocardial infarction (STEMI; n = 417). All
      patients underwent coronary angiography and, if indicated, primary angioplasty
      (STEMI: 417 patients; UA/NSTEMI: 157 patients). The Cox proportional hazards
      regression model was used to evaluate the independent effect of the risk factors
      on the occurrence of primary endpoint, i.e. all-cause mortality during six-year
      follow-up. Survival status and date of death were obtained from the National
      Registry of Population (PESEL database). RESULTS: A total of 123 patients (18.3%)
      died within the post-discharge period. The multivariate analysis identified 11
      highly significant independent predictors of mortality (in order of predictive
      strength): diabetes mellitus (all types), higher creatinine level, older age, and
      more frequent occurrence of: supraventricular arrhythmias during hospitalisation,
      peripheral artery disease, recurrent angina pectoris with documented ischaemia on
      electrocardiogram, male sex, prior myocardial infarction, treatment with intra
      aortic balloon pump counterpulsation, heart failure, and higher peak levels of
      creatine kinase-MB. CONCLUSIONS: The risk factors obtained from the medical
      history and during the hospitalisation improve the risk stratification during the
      post-discharge period after hospitalisation for ACS.

PMID- 29350383
TI  - Which position should we take during newborn resuscitation? A prospective,
      randomised, multicentre simulation trial.
AB  - BACKGROUND: Early bystander cardiopulmonary resuscitation (CPR) for cardiac
      arrest is crucial in the chain of survival. Cardiac arrest in infants is rare,
      but CPR is also performed in severe bradycardia. European Resuscitation Council
      and American Heart Association guidelines recommend continuing CPR until the
      heart muscle is sufficiently oxygenated and regains sufficient contractility and
      function. The most common and recommended CPR techniques that can be applied in
      newborns are the two-finger technique and two-thumb technique. AIM: We sought to
      assess the quality of CPR performed in newborns with the two-finger technique
      depending on the posi-tion of the rescuer during resuscitation. METHODS: This was
      a prospective, randomised, crossover, simulated study. It involved 93 nurses who
      were required to perform a two-minute CPR using the two-finger technique in three
      scenarios: (A) with the newborn lying on the floor; (B) on a table; and (C) with
      the newborn on the rescuer's forearm. The Newborn Tory(r) S2210 manikin was used
      to simulate a neonatal patient in cardiac arrest. The following parameters were
      measured: chest compression (CC) depth, CC rate, no-flow time, percentage of full
      release, ventilation rate, and ventilation volume, as well as the number of
      effective compressions and effective ventilations. RESULTS: Statistical analysis
      showed significant differences in CC rates between scenarios A and B (p < 0.001)
      and between scenarios B and C (p = 0.002). Significant differences were also
      observed between the median CC depth. The median per-centage of no-flow-fraction
      was the highest for scenario A (55%), followed by scenario B (48%), and scenario
      C (46%). There were significant differences between the values of no-flow
      fraction between scenarios A and B (p < 0.001), and between scenarios A and C (p
      < 0.001). The percentage of chest full releases for scenarios A, B, and C
      amounted to 94%, 1%, and 92%, respectively. Significant differences in the number
      of effective CCs between scenarios A and B (p < 0.001) as well as B and C (p <
      0.001) were revealed. The median ventilation rate was highest for scenario B (13
      * min-1), and lowest for scenario A (9 * min-1). The highest tidal volume was
      obtained in scenario A (27 mL), and the lowest in scenario C (26 mL). The most
      effective CPR was performed when resuscitation was carried out on the rescuer's
      forearm. CONCLUSIONS: The quality of CCs in newborns depends on the location of
      the patient and the rescuer. The optimal form of resuscitation of newborns is
      resuscitation on the rescuer's forearm.

PMID- 29350384
TI  - The importance of psychosocial factors in management of pulmonary arterial
      hypertension patients.

PMID- 29350385
TI  - Impact of previous cardiac surgery with sternotomy on clinical outcomes and
      quality of life after transcatheter aortic valve implantation for severe aortic
      stenosis.
AB  - BACKGROUND: Transcatheter aortic valve implantation (TAVI) has evolved as an
      effective treatment in patients with symptomatic severe aortic stenosis (AS) and
      increased operative risk. Data on the influence of previous sternotomy on the
      risk of TAVI are limited. AIM: We sought to investigate the effect of previous
      cardiac surgery with sternotomy on clinical outcomes and quality of life (QoL)
      after TAVI. METHODS: The study included 148 consecutive patients with symptomatic
      severe AS, who underwent TAVI. Baseline charac-teristics, procedural and long
      term clinical outcomes, and QoL assessment with the EQ-5D-3L questionnaire were
      compared between patients with and without previous sternotomy. RESULTS: Patients
      with previous sternotomy (23.0% of the population) were younger and more often
      male, had higher rate of previous myocardial infarction (MI; 26 [22.8%] vs. 22
      [64.7%], p = 0.001), and lower median left ventricular ejection frac-tion (60.0%
      [50.0-65.0] vs. 50.0% [42.0-60.0], p = 0.004). Periprocedural risk measured with
      the Logistic Euroscore and the Society of Thoracic Surgeons scale was comparable
      in both groups. There were no differences in 30-day and 12-month all-cause
      mortality between the groups with and without sternotomy (10 [8.8%] vs. 2 [5.9%],
      p = 0.7; odds ratio [OR] adjusted for age/sex/previous MI, 0.56, 95% confidence
      interval [CI] 0.10-3.29; for 12-month mortality adjusted OR 0.19, 95% CI 0.04
      0.99). At the longest available follow-up, mortality was higher in patients
      without sternotomy (30 [26.3%] vs. 3 [8.8%], p = 0.03; adjusted OR 0.10, 95% CI
      0.02-0.42). Similar rates of other complications after TAVI were noted. No
      differences in the EQ-5D-3L questionnaire at baseline and 12-month follow-up were
      confirmed. CONCLUSIONS: TAVI seems to be a safe and effective technique for the
      treatment of severe AS in patients with previous cardiac surgery.

PMID- 29350386
TI  - Comparison of clinical characteristics of real-life atrial fibrillation patients
      treated with vitamin K antagonists, dabigatran, and rivaroxaban: results from the
      CRAFT study.
AB  - BACKGROUND: The first-line drugs for the treatment of non-valvular atrial
      fibrillation (AF) are non-vitamin K antagonist oral anticoagulants (NOACs), which
      are preferred over vitamin K antagonists (VKAs). There is some evidence that
      there are dis-crepancies between everyday clinical practice and the guidelines.
      AIM: The study aimed to compare the characteristics of patients on VKAs,
      dabigatran, and rivaroxaban in everyday practice (i.e. baseline characteristics,
      drug doses, risk factors for bleeding and thromboembolic events). Additionally,
      we assessed the frequency of prescription of different oral anticoagulants (OACs)
      in recent years. METHODS: This study consisted of data from the multicentre CRAFT
      (MultiCentre expeRience in AFib patients Treated with OAC) study (NCT02987062).
      This was a retrospective analysis of hospital records of AF patients
      (hospitalised in the years 2011-2016) treated with VKAs (acenocoumarol, warfarin)
      and NOACs (dabigatran, rivaroxaban). A total of 3528 patients with non-valvular
      AF were enrolled in the CRAFT study. RESULTS: The total cohort consisted of 1973
      patients on VKA, 504 patients on dabigatran, and 1051 patients on rivaroxaban.
      Patients on rivaroxaban were older (70.5 +/- 13.1 years) and more often female
      (47.9%), compared with those on VKAs (67.0 +/- 12.8 years, p < 0.001; 35.5%, p <
      0.001) and on dabigatran (66.0 +/- 13.9 years, p < 0.001; 38.9%, p = 0.001).
      Among NOACs, patients with persistent and permanent AF were more likely to
      receive rivaroxaban (54.7% and 73.4%, re-spectively) than dabigatran (45.3%, p <
      0.001 and 26.6%, p = 0.002, respectively). Patients on rivaroxaban had higher
      risk of thromboembolic events (CHA2DS2VASc 3.9 +/- 2.0, CHADS2 2.2 +/- 1.4) than
      those on VKAs (3.3 +/- 2.0, 1.9 +/- 1.3) and on dabigatran (3.1 +/- 2.0, 1.8 +/-
      1.3). Patients on rivaroxaban had also a higher rate of prior major bleeding
      (11.2%) than those on VKAs (6.7%, p < 0.001) and on dabigatran (7.3%, p = 0.02).
      Patients on lower doses of dabigatran and rivaroxaban had a significantly higher
      risk of thromboembolic and bleeding events. Use of VKAs in the year 2011 was
      reported in over 96% of patients on OACs, but this proportion decreased to 34.6%
      in 2016. In the last analysed year (2016) AF patients were treated mainly with
      NOACs - dabigatran (24.2%) and rivaroxaban (41.3%). CONCLUSIONS: The prescription
      of VKAs declined significantly after the introduction of NOACs. Patients treated
      with different OACs demonstrated a distinct baseline clinical profile. The
      highest risk of thromboembolic events and incidence of major bleedings was
      observed in patients on rivaroxaban, in comparison to patients on VKAs and
      dabigatran. Among NOACs, patients treated with lower doses of dabigatran and
      rivaroxaban were older and had a significantly higher risk of thromboembolic and
      bleeding events.

PMID- 29350387
TI  - Clinical anatomy of human heart atria and interatrial septum - anatomical basis
      for interventional cardiologists and electrocardiologists. Part 1: right atrium
      and interatrial septum.

PMID- 29350388
TI  - Chronic statin treatment is a predictor of pre-interventional infarct-related
      artery patency in patients with ST elevation myocardial infarction treated with
      percutaneous coronary intervention.
AB  - BACKGROUND: Beyond lipid-lowering effects, early statin treatment has beneficial
      effects on prognosis after acute coronary syndrome. Infarct-related artery (IRA)
      patency before percutaneous coronary intervention (PCI) is known to be a strong
      pre-dictor of improved clinical outcome. AIM: We aimed to investigate the effects
      of chronic statin treatment before admission on IRA patency after myocardial
      infarction. METHODS: In this study, 938 ST elevation myocardial infarction
      (STEMI) patients admitted to the hospital within the first 12 h of symptom onset
      were prospectively enrolled (male, n = 682; female, n = 256; mean age 58.6 +/-
      12.4 years). All patients underwent emergent primary PCI. Patients were divided
      into two groups based upon angiographic IRA patency. Impaired IRA patency was
      defined as Thrombolysis In Myocardial Infarction (TIMI) grade 0 and 1 flow (non
      patent IRA group). Angiographic IRA patency was defined as TIMI 2 and 3 flow
      (patent IRA group). RESULTS: Previous statin usage was more frequent in the
      patent IRA group (n = 138; 71.9%), than in the non-patent IRA group (n = 110;
      14.7%; p < 0.001). Pre-PCI IRA patency was independently associated with body
      mass index (odds ra-tio [OR] = 1.087, 95% confidence interval [CI] 1.005-1.176, p
      < 0.001), previous chronic statin use (OR 0.065, 95% CI 0.043-0.098, p = 0.039),
      ejection fraction (OR 1.041, 95% CI 1.018-1.064, p < 0.001), and SYNTAX score (OR
      0.927, 95% CI 0.899-0.957, p < 0.001) in multivariate logistic regression
      analysis. CONCLUSIONS: Chronic pre-treatment with statins is a significant
      predictor of the IRA patency in patients with STEMI.

PMID- 29350389
TI  - Three-dimensional visualisation of coronary sinus ostium from the inside right
      atrium perspective.
AB  - BACKGROUND: There is no in vivo method of coronary sinus visualisation from the
      right atrium perspective. AIM: The objective of the study was to create a cardiac
      computed tomography (CT) angiography-based method of visualising the coronary
      sinus ostium and the Thebesian valve from the inside right atrium perspective.
      METHODS: In 78 consecutive patients, a cardiac CT angiography (Aquilion 64,
      Toshiba) with retrospective gating (slice 0.5 mm) was performed. Raw data were
      reconstructed on Vitrea 2 workstations (Vital Images). In order to create the
      three-dimensional (3D) coronary sinus visualisation from the "inside view"
      perspective, patented "Fly Through" algorithms were used, and the anatomical
      positions on the multiplanar reconstruction images were marked. A dedicated,
      Likert-based five-point scale was developed and used to evaluate the quality of
      the visualisations. RESULTS: The average quality of the visualisations of the
      coronary sinus ostium in two-dimensional multiplanar reconstruction images was
      good (4.17 +/- 0.85 points) and was clinically interpretable in all cases. The
      image quality of the "inside view" 3D images was 3.61 +/- 1.12 points. In 57.7%
      of cases we obtained high scores (4 and 5 points). The main diameter was 10.72 +/
      2.48 mm, and the entrance angle of the coronary sinus into the right atrium was
      103.76 +/- 10.71 degrees . CONCLUSIONS: Cardiac CT angiography is a useful method
      that permits the coronary sinus ostium and Thebesian valve to be visualised in
      vivo from the inside of the right atrium in a comparable manner.

PMID- 29350390
TI  - Dual antiplatelet therapy is safe and efficient after left atrial appendage
      closure.
AB  - BACKGROUND: Despite results of the PROTECT AF trial, many patients undergoing
      left atrial appendage closure (LAAC) have unconditional contraindications to
      warfarin. AIM: We sought to investigate whether double antiplatelet therapy
      (DAPT) is safe in patients after LAAC. METHODS: Forty-four consecutive patients
      (22 males, mean age 74 +/- 7.8 years) with non-valvular atrial fibrillation
      (NVAF) underwent LAAC procedure using a Watchman device followed by DAPT (75 mg/d
      aspirin and 75 mg/d clopidogrel). After the procedure and during 98 days' follow
      up including transoesophageal echocardiography, peri-procedural complications and
      clinical outcomes were investigated. RESULTS: Mean CHA2DS2-VASc score was 4.9 +/-
      1.5 and mean HAS-BLED score was 3.6 +/- 0.8. The main LAAC indication was
      contraindication to anticoagulation reflected by HAS-BLED score >= 3 observed in
      95.5% cases (among them history of bleeding in 38 patients, 90.5%). 36.4% of
      patients have history of stroke or transient ischaemic attack. The procedure was
      successful in 97.7%. Peri-procedural complications were tamponade (2.3%) and one
      death (2.3%) unrelated to the procedure with no bleeding or vascular
      complications. During follow-up neither stroke nor bleeding were observed,
      whereas two device related thrombi and two unrelated deaths occurred.
      CONCLUSIONS: LAAC followed by DAPT seems to be a safe and efficient alternative
      for stroke prevention in patients with NVAF who have contraindications to
      anticoagulation therapy. This strategy may provide a significant reduction of
      events such as stroke and bleeding versus the score-predicted rate.

PMID- 29350391
TI  - Polish single-centre follow-up of subcutaneous implantable cardioverter
      defibrillator (S-ICD) systems implanted for the prevention of sudden cardiac
      death.
AB  - BACKGROUND AND AIM: Subcutaneous implantable cardioverter-defibrillator (S-ICD)
      is an effective and modern tool used to protect patients at risk of sudden
      cardiac death (SCD) from potentially life-threatening ventricular arrhythmias.
      The first S-ICD systems were implanted in Poland in 2014, but since that time the
      national experience with that therapy has been limited. Our analysis summarises
      the single-centre experience at the Department of Cardiology and Electrotherapy
      of the Medical University of Gdansk with the use of S-ICD from the year 2014 to
      2017. METHODS AND RESULTS: The S-ICD therapy was used in 12 patients (five male,
      seven female, mean age 57.2 +/- 12.5 years), in eight of them for the secondary
      prevention of SCD. No surgical complications of implantation procedures were
      observed during the perioperative hospitalisation nor during follow-up. During
      the mean follow-up of 14 +/- 13 months we observed the appropriate function of
      the systems and a ventricular fibrillation episode successfully terminated by the
      device in one patient, two cases of S-ICD sensing problems (one of which led to
      inadequate intervention of the device), and an episode of atrial fibrillation
      also leading to inadequate intervention in another patient. CONCLUSIONS: S-ICD,
      being an effective and safe method used to treat patients at risk of SCD, may be
      safely and successfully introduced into clinical practice in centres new to that
      field. The number of complications during the initial experience and introduction
      of that method may be kept low if the operating team is experienced enough in
      cardiac electrotherapy.

PMID- 29350392
TI  - Diagnostic and prognostic micro-RNAs in ischaemic stroke due to carotid artery
      stenosis and in acute coronary syndrome: a four-year prospective study.
AB  - BACKGROUND: Circulating microRNAs (miRs) levels are potentially important
      diagnostic and prognostic biomarkers in acute coronary syndrome (ACS) or cerebral
      ischaemic events (CIE) resulting from internal carotid artery stenosis (ICAS).
      AIM: This four-year prospective study aimed to compare the levels of circulating
      miRs in ACS vs. CIE patients, and investigate miRs potentially associated with
      risk of recurrent cardiovascular events. METHODS: The circulating miRs levels
      (miR-1-3p, miR-16-5p, miR-34a-5p, mir-122-5p, miR-124-3p, miR-133a-3p, miR-133b,
      miR-134-5p, miR-208b-3p, miR-375, and miR-499-5p) were compared in 43 (34 men,
      57.6 +/- 10.1 years) patients with ACS, and in 71 (47 men, 69.5 +/- 9.6 years)
      with CIE due to ICAS. A four-year prospective evaluation of miRs associated with
      risk of cardiovascular death (CVD), myocardial infarction (MI), CIE, or all
      (CVD/MI/CIE) was performed. RESULTS: In ACS vs. CIE patients, the levels of miR
      124-3p (p < 0.001), miR-134-5p (p = 0.012), miR-208b-3p (p < 0.001), miR-34a-5p
      (p < 0.001), and miR-499-5p (p < 0.001) were higher, while levels of miR-16-5p (p
      < 0.001) and miR-122-5p (p < 0.001) were lower. Levels of miR-1-3p (p = 0.195),
      miR-133a-3p (p = 0.333), miR-133b (p = 0.056), and miR-375 (p = 0.055) were non
      statistically different. During follow-up (median 57 months, Q1-Q3: 54-60),
      CVD/MI/CIE occurred in 23 subjects, including eight CVDs, five non-fatal CIEs,
      and 10 non-fatal MIs. The multivariate Cox proportional hazard analysis (relative
      risk [RR]; 95% confidence interval [CI]) revealed that miR-208b-3p (1.225; 1.092
      1.375), miR-34a-5p (0.963; 0.935-0.992), and miR-499-5p (0.077; 0.025-0.239) were
      independently associated with risk of CVD/MI/CIE, as well as risk of each event.
      Furthermore, miR-133b (1.009; 1.003-1.015) was associated with risk of CVD.
      CONCLUSIONS: This study shows that although most investigated miRs levels differ
      significantly between patients with ACS and CIE, similar levels of circulating
      miR-1-3p, miR-133a-3p, miR-133b, and miR-375 were observed; furthermore, we
      identified several common miRs as possible risk factors for recurrent
      cardiovascular events.

PMID- 29350393
TI  - Is it possible to improve compliance in hypertension and reduce therapeutic
      inertia of physicians by mandatory periodic examinations of workers?
AB  - BACKGROUND: Due to high prevalence, insufficient recognition, and ineffective
      treatment, hypertension (HT) still remains a major medical and socio-economic
      problem. There is a real necessity to develop effective prophylaxis for
      cardiovascular disorders (CVD), based on strategies that support compliance
      during long-term therapy. The Polish scheme of occupational health services with
      mandatory periodical employee check-ups creates a unique opportunity for
      effective HT prophylaxis. As a result, visiting a doctor is required not only due
      to health ailments but also by law, which is especially important for those
      feeling well. It enables an improvement in tertiary prevention, including actions
      taken not only by the doctors of the occupa-tional health services, but also by
      the physicians in charge of treating the patients. AIM: Evaluation of the
      usefulness of mandatory health check-ups of employees concerning frequency of
      diagnosis and im-provement of treatment outcomes of HT. METHODS: The study group
      comprised 1010 Polish workers referred by their employers for mandatory medical
      examinations. All of the study participants filled in a questionnaire focused on
      self-assessment of their health, current blood pressure (BP) mea-surements, and
      in cases where HT had been previously detected - compliance with medical
      recommendations. Then in the doctor's office BP measurements were taken twice.
      Workers who fulfilled a criterion indicating a need for intervention were
      educated on optimal diet, physical activity, and risk factors for CVD. They also
      received medical instructions for three-step action. The first recommendation:
      measure BP three times a day for one week and record the results. The second:
      visit a gen-eral practitioner (GP) for a professional assessment of those
      results. The third: re-visit the occupational health physician within three
      months. The criterion for intervention was prior HT and a mean of two BP
      measurements >= 180/110 mmHg - in each case, or >= 140/90 mmHg - in the case of
      occupational exposure to risk factors for CVD. RESULTS: The mean age of the study
      participants was 41.7 years (similar in both genders). A previous diagnosis of HT
      was declared by 20.1% of patients. 11% of patients involved in the intervention
      did not comply with medical advice. The current HT therapy of all of the subjects
      with HT (100% of those with abnormal BP, who visited their GP) was modified.
      CONCLUSIONS: Prophylactic medical check-ups of workers gives improved compliance
      and medical surveillance of HT in patients with an uncontrolled clinical course
      of this disease. Obligations and periodic examinations encourage both patients
      and physicians to improve compliance and reduce the risk of therapeutic inertia.

PMID- 29350394
TI  - Genetic variants in a Polish population of patients with pulmonary arterial
      hypertension: sequencing of BMPR2, ALK1, and ENG genes.
AB  - BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare disease with a very
      serious prognosis. It seems that mutations in genes related to transforming
      growth factor-b signalling pathway are often related to the development of the
      disease. No study covers this problem in a Polish population. AIM: To screen for
      genetic mutations in a Polish cohort of patients with pulmonary hypertension,
      especially with idiopathic PAH, treated in a single hospital in Poland. METHODS:
      DNA sequencing method was used. Samples from 50 patients with pulmonary
      hypertension were screened for mutations in type 2 bone morphogenetic protein
      receptor of the transforming growth factor-b superfamily gene (BMPR2). Samples
      from 20 patients with idiopathic PAH (11 men, mean age 55 years) were also
      screened for mutations in activin A receptor-like type 1 gene (ALK1) and endoglin
      gene (ENG). RESULTS: No genetic variations were found for the BMPR2 gene. In all
      20 samples from idiopathic pulmonary hypertension patients we found
      heterozygosity of single nucleotide polymorphism (SNP) rs 372023206 in ALK1 gene.
      Three samples from these patients showed variations of ENG gene: we found one
      sample with heterozygosity of SNP rs 200525684, one with heterozygosity of SNP rs
      3739817, and one with both. CONCLUSIONS: We detected benign polymorphisms or
      genetic variants of unknown importance. It is possible that the Polish population
      of PAH patients differs from the previously described populations of other
      countries in terms of the frequency and importance of mutations in BMPR2, ALK1
      and ENG genes.

PMID- 29350395
TI  - Early results of aortic arch reconstruction and bilateral pulmonary artery
      banding: modification of the Norwood operation for treatment of hypoplastic left
      heart syndrome.
AB  - BACKGROUND: In the period from 2003 to the end of 2015, 96 Norwood I procedures
      were performed in the Paediatric Heart Surgery Department in Katowice, Poland, in
      children with hypoplastic left heart syndrome (HLHS). AIM: This paper presents a
      retrospective analysis of early surgical results. METHODS: The patients consisted
      of two groups: group I included 59 children operated on in the years 2003-2012,
      in whom the stage I Norwood procedure with the Sano modification was performed
      with the aortic arch reconstructed by use of a ho-mogenous pulmonary artery patch
      or a bovine pericardial patch. Group II included 37 children after our
      modification of the Norwood I procedure, in which the aortic arch was
      reconstructed with an extracellular matrix patch and bilateral pulmonary artery
      banding was done. RESULTS: Aortic cross-clamping time was significantly shorter
      in group II (mean 52; range 38-62 min) than in group I (mean 57; range 39-72 min;
      p < 0.009). Eighteen (30.5%) children in group I and six (16.2%) in group II
      died. Although this dif-ference did not reach statistical significance (p =
      0.12), it suggested that improved outcomes with the modified procedure are
      possible. The cause of death in group I was significantly more frequently due to
      massive postoperative bleeding (n = 6; 33.3%) than in group II (n = 1; 16.7%; p =
      0.046). CONCLUSIONS: The introduction of this new surgical technique reduced
      postoperative bleeding rates, shortened the operation time, and might improve the
      mortality rate in the first-stage surgical treatment of children with HLHS.

PMID- 29350396
TI  - Tobacco regulation as a paradigm for advancing regulatory science in dermatology.

PMID- 29350397
TI  - The burden of non-melanoma skin cancers in Auckland, New Zealand.
AB  - BACKGROUND/OBJECTIVES: As the New Zealand Cancer Registry does not require
      mandatory reporting of non-melanoma skin cancers (NMSC), basal cell carcinomas
      (BCC) and squamous cell carcinomas (SCC), the clinical burden of these diseases
      is unknown. METHODS: A retrospective review of all patients with histopathology
      performed allowed us to estimate invasive BCC and SCC in the Auckland region in
      2008 (population 1.44 million). RESULTS: During this period, a total of 21 236
      NMSC were diagnosed among 13 996 patients, consisting of 5611 SCC lesions (26%)
      and 15 525 (74%) BCC. The Auckland incidence rates per 100 000 were 425 for SCC
      and 1177 for BCC. The overall rate of NMSC per 100 000 was 1906.5 (standardised
      to the census data of Australia 2001); 1385 for BCC and 522 for SCC. Using
      published data on incidence trends and population growth, we estimate that 29 000
      33 000 NMSC would have been excised in Auckland in 2016, and 78 000-87 000 in New
      Zealand. CONCLUSION: Auckland has the highest reported incidence of invasive NMSC
      in the world. We believe that high-risk cutaneous SCC and complex BCC should be
      recorded. Our study provides information for clinicians and health economists on
      the scale of the problem.

PMID- 29350398
TI  - Use of Computational Functional Genomics in Drug Discovery and Repurposing for
      Analgesic Indications.
AB  - The novel research area of functional genomics investigates biochemical,
      cellular, or physiological properties of gene products with the goal of
      understanding the relationship between the genome and the phenotype. These
      developments have made analgesic drug research a data-rich discipline mastered
      only by making use of parallel developments in computer science, including the
      establishment of knowledge bases, mining methods for big data, machine-learning,
      and artificial intelligence, (Table ) which will be exemplarily introduced in the
      following.

PMID- 29350399
TI  - Biological functions of Elabela, a novel endogenous ligand of APJ receptor.
AB  - The G protein-coupled receptor APJ and its cognate ligand, apelin, are widely
      expressed throughout human body. They are implicated in different key
      physiological processes such as angiogenesis, cardiovascular functions, fluid
      homeostasis, and energy metabolism regulation. Recently, a new endogenous
      peptidic ligand of APJ, named Elabela, has been identified and shown to play a
      crucial role in embryonic development. In addition, increasing evidences show
      that Elabela is also intimate associated with a large number of physiological
      processes in adulthood. However, a comprehensive summary of Elabela has not been
      reported to date. In this review, we provide an overview of the biological
      functions of Elabela. Collectively, Elabela, a potential therapeutic peptide,
      exerts diverse biological functions in both embryos and adult organisms, such as
      dysontogenesis, self-renewing of human embryonic stem cells, endoderm
      differentiation, heart morphogenesis, cardiac dyfunctions, blood pressure
      control, angiogenesis, blood pressure control, regulation of food and water
      intake, bone formation, and kidney diseases.

PMID- 29350400
TI  - Feasibility of Enteral Protein Supplementation in Critically Ill Children.
AB  - BACKGROUND: We describe the protein type and concentration in standard enteral
      nutrition (EN) formulas and the effect of protein supplementation on the
      osmolality of standard formulas. We also aimed to examine factors associated with
      optimal protein delivery in critically ill children. METHODS: Protein content and
      other characteristics of pediatric EN formulas used worldwide were recorded.
      Factors associated with achievement of recommended protein delivery and tolerance
      of protein-supplemented formulas were recorded prospectively in a cohort of
      critically ill children. A range of protein supplement doses was added to 2
      standard formulas and water, and the osmolality was recorded by cryoscopy in a
      bench experiment. RESULTS: We reviewed 125 formulas used in a multicenter study
      including sites from >13 countries. A majority of the EN formulas (73.6%) were
      polymeric, with a nonprotein calorie/nitrogen ratio of 182 +/- 66 and protein
      content of 3.53 +/- 2.00 g/100 mL. In the cohort of critically ill children,
      28.5% achieved protein intake goal within 4 days, with no intolerance. In
      addition to optimal protein prescription (P < 0.001), protein supplementation (P
      = 0.018) and early EN initiation (P = 0.006) were associated with significantly
      higher odds of achieving goal protein intake. Formulas supplemented with up to 8
      g/100 mL polymeric protein had osmolality <450 mOsm/kg. CONCLUSIONS: The protein
      content of current pediatric formulas may be inadequate to meet the needs of
      critically ill children. Protein supplementation of formulas allows early
      achievement of goal and is likely to be safe.).

PMID- 29350401
TI  - Neurodevelopmental outcome in very preterm and very-low-birthweight infants born
      over the past decade: a meta-analytic review.
AB  - AIM: The purpose of this systematic review was to provide an up-to-date global
      overview of the separate prevalences of motor and cognitive delays and cerebral
      palsy (CP) in very preterm (VPT) and very-low-birthweight (VLBW) infants. METHOD:
      A comprehensive search was conducted across four databases. Cohort studies
      reporting the prevalence of CP and motor or cognitive outcome from 18 months
      corrected age until 6 years of VPT or VLBW infants born after 2006 were included.
      Pooled prevalences were calculated with random-effects models. RESULTS: Thirty
      studies were retained, which included a total of 10 293 infants. The pooled
      prevalence of cognitive and motor delays, evaluated with developmental tests, was
      estimated at 16.9% (95% confidence interval [CI] 10.4-26.3) and 20.6% (95% CI
      13.9-29.4%) respectively. Mild delays were more frequent than moderate-to-severe
      delays. Pooled prevalence of CP was estimated to be 6.8% (95% CI 5.5-8.4).
      Decreasing gestational age and birthweight resulted in higher prevalences. Lower
      pooled prevalences were found with the Third Edition of the Bayley Scales of
      Infant Development than with the Second Edition. INTERPRETATION: Even though
      neonatal intensive care has improved over recent decades, there is still a wide
      range of neurodevelopmental disabilities resulting from VPT and VLBW births.
      However, pooled prevalences of CP have diminished over the years. WHAT THIS PAPER
      ADDS: The Bayley Scales of Infant and Toddler Development, Third Edition reported
      lower pooled prevalences of motor and cognitive delays than the Second Edition.
      The pooled prevalence of cerebral palsy in infants born extremely preterm was
      reduced compared with previous meta-analyses.

PMID- 29350402
TI  - Effectiveness and safety of original and generic sofosbuvir for the treatment of
      chronic hepatitis C: A real world study.
AB  - We report the first real-world prospective multicenter cohort study that
      evaluated the effectiveness and safety of original or generic sofosbuvir-based
      regimens in patients with chronic hepatitis C in Latin America. The main
      endpoints were assessment of sustained virological response and serious adverse
      events rates. A total of 321 patients with chronic hepatitis C treated with the
      following regimens were included: sofosbuvir plus daclatasvir for 12 (n = 34) or
      24 (n = 135) weeks, sofosbuvir plus daclatasvir plus ribavirin for 12 (n = 84) or
      24 (n = 56) weeks, or sofosbuvir plus ribavirin for 12 (n = 8) or 24 (n = 2)
      weeks. Patients received either original sofosbuvir (Sovaldi(r) , Gilead
      Sciences, n = 135) or generic sofosbuvir (Probirase(r) , Laboratorios RICHMOND, n
      = 184) which were randomly assigned by the National Ministry of Health. Overall,
      292 (91%) patients had cirrhosis, 136 (42%) were treatment experienced, and 240
      (75%) genotype 1. The overall sustained virological response was 90% (95% CI 86
      93%); 91% (95% CI 84-95%) in patients who received Sovaldi(r) , and 89% (95% CI
      84-93%) in patients who received Probirase(r) . Anemia was the most common
      adverse event and was reported in 52 (17%) patients. Bacterial infection,
      gastrointestinal bleeding, worsening of ascites or encephalopathy occurred in
      less than 5% of the patients. During the study, seven (2%) patients died, four of
      whom died of cirrhosis-related complications. In summary, we observed similar
      sustained virological response rates than prior studies, both in patients who
      received Sovaldi(r) or Probirase(r) . Serious adverse events were infrequent, in
      line with prior studies that included patients with cirrhosis treated with
      protease-inhibitor-free regimes.

PMID- 29350403
TI  - Influence of Contrast Administration on Computed Tomography-Based Analysis of
      Visceral Adipose and Skeletal Muscle Tissue in Clear Cell Renal Cell Carcinoma.
AB  - BACKGROUND: Computed tomography (CT) scans are being utilized to examine the
      influence of skeletal muscle and visceral adipose quantity and quality on health
      related outcomes in clinical populations. However, little is known about the
      influence of contrast administration on these parameters. METHODS: Precontrast,
      arterial, and 3-minute postcontrast CT images of 45 patients with clear cell
      renal cell carcinoma were downloaded from The Cancer Imaging Archive and
      retrospectively analyzed for visceral adipose cross-sectional area (CSA) and
      density, and muscle CSA and density at the third lumbar vertebrae. Low muscle CSA
      index was defined as <=38.9 cm2 /m2 for women and <=55.4 cm2 /m2 for men. Low
      muscle density was defined as <41 Hounsfield units (HU) for body mass index (BMI)
      <24.9 kg/m2 and <33 HU for BMI >=25.0 kg/m2 . RESULTS: In both the arterial and 3
      minute phases, contrast administration decreased visceral adipose CSA (-20.9 and 
      20.9 cm2 ; P < .001) and increased visceral adipose density (4.8 and 5.8 HU; P <
      .001), relative to precontrast images. Muscle CSA index marginally increased in
      the arterial (0.6 cm2 /m2 ; P = .007) and 3-minute phases (0.8 cm2 /m2 ; P <
      .001). This likely represents clinically insignificant changes because it does
      not alter the identification of low muscle CSA (44.4% vs 42.2%; P = 1.00).
      Skeletal muscle density increased in the arterial (6.4 HU; P < .001) and 3-minute
      phases (8.7 HU; P < .001), which altered the identification of low muscle density
      (6.7% vs 31.1%; P < .001). CONCLUSIONS: Future analyses should consider the phase
      of contrast during CT imaging because it may alter the interpretations of several
      parameters.

PMID- 29350404
TI  - Gastrointestinal protists and helminths of habituated agile mangabeys (Cercocebus
      agilis) at Bai Hokou, Central African Republic.
AB  - Infectious diseases including those caused by parasites can be a major threat to
      the conservation of endangered species. There is thus a great need for studies
      describing parasite infections of these species in the wild. Here we present data
      on parasite diversity in an agile mangabey (Cercocebus agilis) group in Bai
      Hokou, Dzanga-Sangha Protected Areas (DSPA), Central African Republic. We
      coproscopically analyzed 140 mangabey fecal samples by concentration techniques
      (flotation and sedimentation). Agile mangabeys hosted a broad diversity of
      protistan parasites/commensals, namely amoebas (Entamoeba spp., Iodamoeba
      buetschlli), a Buxtonella-like ciliate and several parasitic helminths:
      strongylid and spirurid nematodes, Primasubulura sp., Enterobius sp., and
      Trichuris sp. Importantly, some of the detected parasite taxa might be of
      potential zoonotic importance, such as Entamoeba spp. and the helminths
      Enterobius sp., Trichuris sp., and strongylid nematodes. Detailed morphological
      examination of ciliate cysts found in mangabeys and comparison with cysts of
      Balantioides coli from domestic pigs showed no distinguishing structures,
      although significant differences in cyst size were recorded. Scanning or
      transmission electron microscopy combined with molecular taxonomy methods are
      needed to properly identify these ciliates. Further studies using molecular
      epidemiology are warranted to better understand cross-species transmission and
      the zoonotic potential of parasites in sympatric non-human primates and humans
      cohabiting DSPA.

PMID- 29350406
TI  - Cutaneous hyperpigmentation induced by apremilast.

PMID- 29350405
TI  - Reactive oxygen species-induced parthanatos of immunocytes by human
      cytomegalovirus-associated substance.
AB  - Previous studies have examined various immune evasion strategies of human
      cytomegalovirus (HCMV) to gain understanding of its pathogenesis. Although the
      mechanism that underlies immunocyte destruction near HCMV-infected lesions has
      yet to be established, it is here shown that substances produced by HCMV-infected
      cells induce death in several types of immunocytes, but not in fibroblasts or
      astrocytomas. These substances contain HCMV proteins and were termed HCMV
      associated insoluble substance (HCMVAIS). The mechanism by which HCMVAIS induces
      cell death was characterized to improve understanding the death of immunocytes
      near HCMV-infected lesions. HCMVAIS were found to trigger production of
      intracellular nicotinamide adenine dinucleotide phosphate oxidase-derived
      reactive oxygen species (ROS), resulting in cell death, this effect being
      reversed following treatment with ROS inhibitors. Cell death was not induced in
      splenocytes from NOX-2 knockout mice. It was hypothesized that DNA damage induced
      by oxidative stress initiates poly ADP-ribose polymerase-1 (PARP-1)-mediated cell
      death, or parthanatos. HCMVAIS-induced cell death is accompanied by PARP-1
      activation in a caspase-independent manner, nuclear translocation of apoptosis
      inducing factor (AIF), and DNA fragmentation, which are typical features of
      parthanatos. Treatment with an AIF inhibitor decreased the rate of HCMVAIS
      induced cell death, this being confirmed by hematoxylin and eosin staining; cell
      death in most HCMV-positive foci in serial section samples of a large intestine
      with HCMV infection was TUNEL-positive, cleaved caspase 3-negative and CD45
      positive. Taken together, these data suggest that HCMV inhibits local immune
      responses via direct killing of immunocytes near HCMV-infected cells through ROS
      induced parthanatos by HCMVAIS.

PMID- 29350407
TI  - Recent progress in the antiviral activity and mechanism study of pentacyclic
      triterpenoids and their derivatives.
AB  - Viral infections cause many serious human diseases with high mortality rates. New
      drug-resistant strains are continually emerging due to the high viral mutation
      rate, which makes it necessary to develop new antiviral agents. Compounds of
      plant origin are particularly interesting. The pentacyclic triterpenoids (PTs)
      are a diverse class of natural products from plants composed of three terpene
      units. They exhibit antitumor, anti-inflammatory, and antiviral activities.
      Oleanolic, betulinic, and ursolic acids are representative PTs widely present in
      nature with a broad antiviral spectrum. This review focuses on the recent
      literatures in the antiviral efficacy of this class of phytochemicals and their
      derivatives. In addition, their modes of action are also summarized.

PMID- 29350408
TI  - Calibration and non-orthogonality correction of three-axis Hall sensors for the
      monitoring of MRI workers' exposure to static magnetic fields.
AB  - A Magnetic Resonance Imaging (MRI) scanner uses three different electromagnetic
      fields (EMF) to produce body images: a static permanent magnetic field (MF),
      several pulsed magnetic gradients, and a radiofrequency pulse. As a result, any
      occupation that includes an MRI exposes workers to a strong MF. The World Health
      Organization has now given the monitoring of occupational EMF exposure a high
      priority. One design for a low-cost, compact MF exposure monitor (" MR
      exposimeter ") uses a set of three orthogonally assembled Hall sensors. However,
      at such a strong EMF exposure intensity, the non-linearity and non-orthogonality
      (misalignment between the three Hall sensors) have an impact on the accuracy of
      EMF measurement. Therefore, a sensor characterization was performed in order to
      link Hall-effect output voltage to MF intensity. The sensor was then calibrated
      using an orthogonalization matrix and an offset vector. For each sensor
      configuration, the matrix and vector parameters were optimized with a calibration
      set generated by the movement of a three-axis sensor inside homogeneous MF areas.
      Once calibrated, the sensor was tested at different MF intensities and returned
      accuracy improvements. This calibration procedure was tested on synthetic data
      and performed on experimental data. The calibration parameters can be easily
      reused by the user, and their stability could be used as a quality control
      sensor. Finally, real-time monitoring test for static MF exposure was completed
      and validated on an MRI worker during a typical working day. Bioelectromagnetics.
      39:108-119, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 29350409
TI  - Comparison of lesional skin c-KIT mutations with clinical phenotype in patients
      with mastocytosis.
AB  - BACKGROUND: Activating c-KIT mutations cause abnormal mast cell growth and appear
      to play a role in mastocytosis. However, the correlation of c-KIT mutations with
      disease phenotypes is poorly characterized. AIM: To evaluate the correlation of c
      KIT mutations with clinical presentations and laboratory findings. METHODS: Total
      cellular RNA was isolated from the skin lesions of 43 adults and 7 children with
      mastocytosis, and PCR amplicons of cDNA were sequenced for c-KIT mutations.
      RESULTS: The most common activating mutation, KIT-D816V, was identified in 72% of
      adults and 57% of children. Additional activating mutations, namely, V560G and
      the internal tandem duplications (ITDs) 502-503dupAY, were detected in 12% of
      adults and 8% of children. V560G occurred more commonly in our patients than
      previously reported, and it appeared to be associated with more advanced disease.
      Otherwise, the presence or absence of activating mutations did not correlate with
      skin lesion morphology, disease extent or total serum tryptase levels. Four
      adults had expression only of wild-type KIT, while two others had expression of a
      truncated KIT lacking tyrosine kinase activity; yet these patients were
      clinically indistinguishable from those patients with activating c-KIT mutations.
      CONCLUSIONS: Activating c-KIT mutations exist in a significant portion of
      patients with mastocytosis, but not all patients showed expression of these
      mutations. Except for V560G, the presence or absence of activating c-KIT
      mutations did not predict the extent of disease. These observations suggest that
      although activating c-KIT mutations are associated with mast cell growth, other
      genes probably play a role in the cause of mastocytosis.

PMID- 29350410
TI  - Misidentification of recombinant hepatitis C virus leading to treatment failure
      with direct acting antivirals.
AB  - The use of new Direct Acting Antivirals, specific of HCV, has greatly improved
      the HCV treatment. Most of the DAA are specific of HCV genotypes. Genotyping
      methods may target different regions of the HCV genome, though only the whole
      genome sequencing could confirm the correct genotype. The present study describes
      the virological investigation of a treatment failure due to the false
      identification of an unusual 2k/1b recombinant HCV form. It describes the
      sequencing methods, and the similarity analysis of the sequences to different
      genotype query sequences, to identify the recombination breakpoint.

PMID- 29350411
TI  - Goals and practicalities of immunoblotting and immunohistochemistry: A guide for
      submission to the British Journal of Pharmacology.

PMID- 29350412
TI  - Surgical repair of propagating condylar fractures of the third
      metacarpal/metatarsal bones with cortical screws placed in lag fashion in 26
      racehorses (2007-2015).
AB  - BACKGROUND: Despite the recommendation of plate fixation for propagating condylar
      fractures of the third metacarpal (McIII) or third metatarsal bone (MtIII), lag
      screw fixation can be a viable surgical option. OBJECTIVES: To evaluate short
      term outcome and long-term racing performance of horses that underwent lag screw
      fixation of long condylar fractures of the McIII/MtIII. STUDY DESIGN:
      Retrospective case series. METHODS: Medical records, post-surgical racing
      performance and outcome of 26 horses with propagating fractures of the medial
      and/or lateral condyle of McIII/MtIII were reviewed. Medical information included
      were age, breed, sex, physical examination at admission, circumstances of
      fracture, radiographic evaluation, anaesthesia and recovery records, surgical and
      post-operative management, as well as complications. Outcome included racing data
      and information from telephone interviews. RESULTS: Twenty-six horses (9
      Standardbreds and 17 Thoroughbreds) were admitted with a long condylar fracture
      of the McIII/MtIII. Fore- and hindlimbs were equally represented with the left
      hindlimb being more frequently involved. Most of the fractures had a spiralling
      component (76%) and four (15%) were comminuted. Fifteen (58%) horses raced post
      surgery including nine Standardbreds (100%) and six Thoroughbreds (35%). Twelve
      of them were placed in at least one race and 11 won at least once. One horse
      sustained a severe complication in recovery. No significant difference was
      observed in the racing performances before and after surgery. MAIN LIMITATIONS:
      Follow-up method and duration were not standardised and there is a low number of
      cases with six surgeons. CONCLUSIONS: Long condylar fractures can be repaired
      using lag fashion technique combined with a half-limb or full-limb tight cast for
      recovery as a good surgical alternative. Similar results to plate fixation can be
      expected, with a return to racing of more than 50%, and the prognosis being even
      better for pacers.

PMID- 29350413
TI  - Occupational exposure to extremely low-frequency magnetic fields and the risk of
      ALS: A systematic review and meta-analysis.
AB  - We performed a meta-analysis to examine associations of occupational exposure to
      extremely-low frequency magnetic fields (ELF-MF) with amyotrophic lateral
      sclerosis (ALS). Epidemiologic studies were identified in EMBASE and MEDLINE, in
      reference lists and a specialist database. We included studies that reported risk
      estimates of ALS in association with occupational ELF-MF exposure. Summary
      relative risks (RR) or odds ratios (OR) were obtained with random effect meta
      analysis, and analyses were stratified by type of exposure assessment. This was
      done to evaluate whether observed heterogeneity between studies could be
      explained with differences in the way the exposure had been determined. We
      included 20 studies in our meta-analysis. Overall, studies reported a slightly
      increased risk of ALS in those exposed to higher levels of ELF-MF compared to
      lower levels with a summary RR (sRR) of 1.14 (95% Confidence Interval [CI] 1.00
      1.30) and for workers in electrical occupations (sRR 1.41, CI 1.05-1.92), but
      with large heterogeneity between studies (I2  > 70%). Self-reported exposure or
      occupations determined from death certificates did not show increased risks.
      Highest-longest types of exposure translated into increased risks of ALS if the
      studies had evaluated the whole occupational history, in contrast to evaluating
      only few points in time (e.g., from census records); sRR were 1.89 (CI 1.31-2.73,
      I2 0%) and 1.06 (CI 0.75-1.57, I2 76%), respectively. In this meta-analysis, we
      observed an increased risk of ALS in workers occupationally exposed to ELF-MF.
      Results of studies depended on the quality of the exposure assessment.
      Bioelectromagnetics. 39:156-163, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 29350414
TI  - Ross River virus in Australian blood donors: possible implications for blood
      transfusion safety.
AB  - BACKGROUND: Emerging transfusion-transmissible pathogens, including arboviruses
      such as West Nile, Zika, dengue, and Ross River viruses, are potential threats to
      transfusion safety. The most prevalent arbovirus in humans in Australia is Ross
      River virus (RRV); however, prevalence varies substantially around the country.
      Modeling estimated a yearly risk of 8 to 11 potentially RRV-viremic fresh blood
      components nationwide. This study aimed to measure the occurrence of RRV viremia
      among donors who donated at Australian collection centers located in areas with
      significant RRV transmission during one peak season. STUDY DESIGN AND METHODS:
      Plasma samples were collected from donors (n = 7500) who donated at the selected
      collection centers during one peak season. Viral RNA was extracted from
      individual samples, and quantitative reverse transcription-polymerase chain
      reaction was performed. RESULTS: Regions with the highest rates of RRV
      transmission were not areas where donor centers were located. We did not detect
      RRV RNA among 7500 donations collected at the selected centers, resulting in a
      zero risk estimate with a one-sided 95% confidence interval of 0 to 1 in 2019
      donations. CONCLUSION: Our results suggest that the yearly risk of collecting a
      RRV-infected blood donation in Australia is low and is at the lower range of
      previous risk modeling. The majority of Australian donor centers were not in
      areas known to be at the highest risk for RRV transmission, which was not taken
      into account in previous models based on notification data. Therefore, we believe
      that the risk of RRV transfusion transmission in Australia is acceptably low and
      appropriately managed through existing risk management, including donation
      restrictions and recall policies.

PMID- 29350415
TI  - Diagnoses and ordering practices driving blood demand for treatment of anemia in
      Tanzania.
AB  - BACKGROUND: Resource-limited countries in Africa experience blood shortages.
      Understanding clinical drivers of blood demand can inform strategies to increase
      blood availability. STUDY DESIGN AND METHODS: From a national representative
      sample of 42 hospitals in Tanzania, patient records and requests for whole blood
      (WB) and red blood cells (RBCs) to treat anemia were analyzed using data
      collected prospectively from June through September 2013. Abstracted data
      included cause of anemia, number of requested units, clinical signs, and
      pretransfusion hemoglobin (Hb) levels. Weighted projections of nationwide drivers
      of blood demand for the year, 2013, were calculated. Mean posttransfusion Hb
      levels were estimated, and blood requests were assessed for clinical
      appropriateness. RESULTS: Malaria was the leading driver of blood demand for
      anemia among children, accounting for 67% (55,949 units; standard deviation [SD],
      1911 units) of projected units requested for children in 2013. Maternal
      hemorrhage was the leading driver of blood demand for anemia among adults,
      accounting for 21% (31,321 units; SD, 963 units) of projected units requested.
      Seventeen percent (26,133 units; SD, 1013 units) of projected requested units
      were deemed inappropriate. Adults with severe anemia had a mean Hb level of 3.7
      g/dL and a mean of 1.6 WB or RBC units per request, resulting in an estimated
      mean posttransfusion Hb level of 5.3 g/dL. CONCLUSIONS: Strategies to prevent and
      treat underlying causes of anemia and decrease inappropriate blood requests will
      likely increase blood availability. Restrictive blood ordering practices seen in
      adults with severe anemia suggests undertreatment of anemia and may result in an
      underestimation of the national blood demand.

PMID- 29350416
TI  - Acute hemorrhagic lesions in an immunosuppressed patient.

PMID- 29350417
TI  - Hepatitis C virus core protein induces dysfunction of liver sinusoidal
      endothelial cell by down-regulation of silent information regulator 1.
AB  - Hepatic fibrosis is a frequent feature of chronic hepatitis C virus (HCV)
      infection. Some evidence has suggested the potential role of silent information
      regulator 1 (SIRT1) in organ fibrosis. The aim of this study was to investigate
      the effect of HCV core protein on expression of SIRT1 of liver sinusoidal
      endothelial cell (LSEC) and function of LSEC. LSECs were co-cultured with HepG2
      cells or HepG2 cells expressing HCV core protein and LSECs cultured alone were
      used as controls. After co-culture, the activity and expression levels of mRNA
      and protein of SIRT1 in LSEC were detected by a SIRT1 fluorometric assay kit,
      real time-PCR (RT-PCR), Western blot, respectively. The levels of adiponectin
      receptor 2 (AdipoR2), endothelial nitric oxide synthase (eNOS) and vascular
      endothelial growth factor (VEGF) were measured by Western blot. Cluster of
      differentiation 31 (CD31), CD14, and von Willebrand factor (vWf) of LSECs was
      performed by flow cytometry. The level of reactive oxygen species (ROS) was
      assayed. Malondialdehyde (MDA), superoxide dismutase (SOD), adiponectin, nitric
      oxide (NO), and endothelin-1 (ET-1) levels in the co-culture supernatant were
      measured. The co-culture supernatant was then used to cultivate LX-2 cells. The
      levels of alpha-smooth muscle actin (ASMA) and transforming growth factor-beta1
      (TGF-beta1) protein in LX-2 cells were measured by Western blot. Compared with
      LSEC co-cultured with HepG2 cells group, in LSEC co-cultured with HepG2-core
      cells group, the activity and expression level of mRNA and protein of SIRT1
      reduced; the level of adiponectin reduced and the expression level of AdipoR2
      protein decreased; ROS levels increased; the expression level of eNOS, VEGF
      protein decreased; and the expression level of CD14 decreased; the expression
      level of vWf and CD31 increased; NO and SOD levels decreased; whereas ET-1 and
      MDA levels increased; the levels of ASMA and TGF-beta1 protein in LX-2 cells
      increased. SIRT1 activator improved the above-mentioned changes. HCV core protein
      may down-regulate the activity and the expression of SIRT1 of LSEC, then
      decreasing synthesis of adiponectin and the expression of AdipoR2, thus inducing
      contraction of LSEC and hepatic sinusoidal capillarization and increasing
      oxidative stress, ultimately cause hepatic stellate cell (HSC) activation.
      Treatment with SIRT1 activator restored the function of LSEC and inhibited the
      activation of HSC.

PMID- 29350418
TI  - Species differences in circulation and inflammatory responses in children with
      common respiratory adenovirus infections.
AB  - Human adenoviruses (HAdVs) cause severe inflammatory respiratory infections, but
      previous epidemiological studies lacked analysis of the characteristics of the
      inflammation. Consecutive patients <13 years old with acute febrile illness
      during a 2-year period were tested. HAdV strains were isolated from
      nasopharyngeal swabs, and molecular identification was performed by hexon, fiber,
      and species-specific PCR methods. Blood inflammatory markers, including the white
      blood cell (WBC) count, CRP, and 29 cytokines, were measured. A total of 187
      patients were enrolled, and HAdV types were identified from 175 patients (93.5%).
      Species C (types 2, 1, 5, and 6, in order of frequency) was most common at 37.1%,
      followed by B (type 3) at 30.9% and E (type 4) at 26.9%. Species C was detected
      predominantly in 1-year-old, whereas B and E were in older ages. Species C and B
      had seasonal circulation patterns, but E was found in only one season during the
      2-year study period. The WBC count was highest in patients with species C. Eleven
      of the 29 tested serum cytokines were detected. Seven kinds, including G-CSF, IL
      6, and TNF-alpha, were elevated in species C infections, whereas IL-10 was lowest
      in species C. Species differences in inflammatory responses, especially regarding
      serum cytokines were described in common pediatric HAdV infections. Species C
      causes the strongest inflammatory responses in young children.

PMID- 29350420
TI  - Over-expression of DEC1 inhibits myogenic differentiation by modulating MyoG
      activity in bovine satellite cell.
AB  - Differentiated embryo chondrocyte 1 (DEC1), a member of basic-helix-loop-helix
      transcription factor Bhlhe40, also called stimulated by retinoic acid 13, STRA13,
      plays an important role in the regulation of adipogenesis, tumorigenesis,
      peripheral circadian output, response to hypoxia, and development of metabolic
      syndrome. Previous studies suggested that DEC1 was involved in skeletal muscle
      development; however, its precise role in myoblast differentiation has not been
      determined. In the present study, we showed that DEC1 expressed ubiquitously in
      different bovine tissues and was down-regulated in differentiated bovine
      satellite cells. Expression of muscle specific transcription factors (Myf5, MyoD,
      MyoG, and MHC) was significantly down-regulated when DEC1 was over-expressed by
      both CoCl2 -simulated hypoxia and Adenovirus-mediated transduction in bovine
      satellite cells. Consistent with that, promoter analyses via luciferase reporter
      assay also revealed that overexpression of bovine DEC1 could inhibit MyoG
      promoter activity. In conclusion, overexpression of DEC1 blocked myogenesis by
      inhibiting MyoG promoter activity in bovine. Our results provided a new mechanism
      for the muscle growth, which would contribute to increase cattle meat
      productivity.

PMID- 29350421
TI  - Involvement of xanthine oxidase inhibition with the antioxidant property of
      nanoencapsulated Melaleuca alternifolia essential oil in fish experimentally
      infected with Pseudomonas aeruginosa.
AB  - Nanoencapsulated Melaleuca alternifolia essential oil (tea tree oil, TTO) is a
      natural alternative treatment, with 100% therapeutic efficacy in fish
      experimentally infected with Pseudomonas aeruginosa, and has also potent
      protective effects linked with antioxidant properties. However, the pathways
      responsible for the antioxidant capacity remain unknown. Thus, this study
      evaluated whether the inhibition of seric xanthine oxidase (XO) activity can be
      considered a pathway involved in the antioxidant capacity of nanoencapsulated TTO
      in fish experimentally infected with P. aeruginosa. Seric samples from fish
      infected with P. aeruginosa showed increased XO activity, as well as increased
      uric acid and reactive oxygen species (ROS) levels. In contrast, the prophylactic
      treatment with nanoencapsulated TTO prevented these infection-induced
      alterations. Based on the evidence obtained, the upregulation of seric XO
      activity induced pro-oxidative effects in the serum of fish experimentally
      infected with P. aeruginosa, due to excessive formation of uric acid, which
      stimulates the release of ROS. This treatment was able to prevent the upregulated
      seric XO activity and, consequently, the excessive formation of uric acid and
      ROS. In summary, inhibition of seric XO activity can be considered a pathway
      involved in the antioxidant capacity of nanoencapsulated TTO in fish
      experimentally infected with P. aeruginosa.

PMID- 29350419
TI  - An integrated framework for the role of oxytocin in multistage social decision
      making.
AB  - Interest in the effects of oxytocin on social behavior has persisted even as an
      overarching theory describing these effects has remained largely elusive. Some of
      the earliest studies on the effects of oxytocin on social decision-making
      indicated that oxytocin might enhance prosocial actions directed toward others.
      This led to development of the prosocial hypothesis, which stipulates that
      oxytocin specifically enhances prosocial choices. However, further work indicated
      that oxytocin administration could elicit antisocial behaviors as well in certain
      social situations, highlighting the importance of context-dependent effects. At
      least two prominent hypotheses have been used to explain these seemingly
      contradictory findings. The social salience hypothesis indicates that the effects
      of oxytocin can be conceptualized as a general increase in the salience of social
      stimuli in the environment. Distinctly, the approach/withdrawal hypothesis
      stipulates that oxytocin enhances approach behaviors and decreases withdrawal
      behaviors. These phenomenologically motivated hypotheses regarding the effects of
      oxytocin on social behavior have created controversies in the field. In this
      review, we present a multistage framework of social decision-making designed to
      unify these disparate theories in a process common to all social decisions. We
      conceptualize this process as involving multiple distinct computational steps,
      including sensory input, sensory perception, valuation, decision formulation, and
      behavioral output. Iteratively, these steps generate social behaviors, and
      oxytocin could be acting on any of these steps to exert its effects. In support
      of this framework, we examine both behavioral and neural evidence across rodents,
      non-human primates, and humans, determining at what point in our multistage
      framework oxytocin could be eliciting its socially relevant effects. Finally, we
      postulate based on our framework that the prosocial, social salience, and
      approach/withdrawal hypotheses may not be mutually exclusive and could explain
      the influence of oxytocin on social behavior to different extents depending on
      context.

PMID- 29350422
TI  - Potency of polycyclic aromatic hydrocarbons in chicken and Japanese quail
      embryos.
AB  - Birds are receptors of concern for polycyclic aromatic hydrocarbons (PAHs), yet
      limited data describing the relative potency of PAH congeners are available for
      avian species. In the present study, we determined embryonic median lethal dose
      (LD50) values for 5 PAH congeners in chicken (Gallus gallus) and one PAH congener
      in Japanese quail (Coturnix japonica). Graded concentrations of each test
      compound were injected into the air cell of chicken or quail eggs before
      incubation. Embryos were monitored through development (quail) or hatching
      (chicken). All PAHs tested caused dose-dependent increases in embryo mortality,
      but few other effects (e.g., weight changes, deformities) were observed. In
      chicken, windows of developmental sensitivity were identified between embryonic
      days 4 and 9 and between embryonic days 20 and 22. The rank order potency of
      benzo[k]fluoranthene (BkF; 76 MUg/kg) ~ dibenz[ah]anthracene (83 MUg/kg) >
      indeno[1,2,3-cd]pyrene (325 MUg/kg) > benzo[a]pyrene (461 MUg/kg) >
      benz[a]anthracene (529 MUg/kg) corresponded well with previous in vitro estimates
      in birds. Previously published ethoxyresorufin-O-deethylase median effect
      concentrations from cultured chicken embryo hepatocytes were highly predictive of
      our LD50s (p < 0.001, r2  = 0.99). To explore differences in sensitivity between
      species, Japanese quail eggs were injected with BkF, the most potent PAH. We
      found that chicken and quail were nearly equally sensitive to BkF. The present
      results contribute to our developing understanding of variability in responses to
      PAHs among congeners and species. Environ Toxicol Chem 2018;37:1556-1564. (c)
      2018 SETAC.

PMID- 29350423
TI  - Ephrin-A1-EphA4 signaling negatively regulates myelination in the central nervous
      system.
AB  - During development of the central nervous system not all axons are myelinated,
      and axons may have distinct myelination patterns. Furthermore, the number of
      myelin sheaths formed by each oligodendrocyte is highly variable. However, our
      current knowledge about the axo-glia communication that regulates the formation
      of myelin sheaths spatially and temporally is limited. By using axon-mimicking
      microfibers and a zebrafish model system, we show that axonal ephrin-A1 inhibits
      myelination. Ephrin-A1 interacts with EphA4 to activate the ephexin1-RhoA-Rock
      myosin 2 signaling cascade and causes inhibition of oligodendrocyte process
      extension. Both in myelinating co-cultures and in zebrafish larvae, activation of
      EphA4 decreases myelination, whereas myelination is increased by inhibition of
      EphA4 signaling at different levels of the pathway, or by receptor knockdown.
      Mechanistically, the enhanced myelination is a result of a higher number of
      myelin sheaths formed by each oligodendrocyte, not an increased number of mature
      cells. Thus, we have identified EphA4 and ephrin-A1 as novel negative regulators
      of myelination. Our data suggest that activation of an EphA4-RhoA pathway in
      oligodendrocytes by axonal ephrin-A1 inhibits stable axo-glia interaction
      required for generating a myelin sheath.

PMID- 29350424
TI  - Prevalence of high-grade cervical intraepithelial neoplasia in women with
      persistent high-risk HPV genotypes and negative cytology.
AB  - INTRODUCTION: Primary HPV screening will be implemented into the English Cervical
      Screening Programme by 2019. Its impact upon women referred to colposcopy, with
      negative cytology but persistently positive high-risk HPV (hrHPV), remains
      unreported from UK Sentinel sites. HPV primary screening was introduced in
      Sheffield, UK in April 2013; this paper reports its impact on the service.
      METHODS: A retrospective cohort study was performed from June 2014 to July 2016
      at the Jessop Wing Colposcopy Unit, Sheffield. UK. Data were obtained from the
      pathology and colposcopy databases and cross-referenced with case-notes and
      pathology results for women referred with persistently positive hrHPV, cytology
      negative samples. Patient demographics, hrHPV genotype, biopsy rates,
      histological diagnoses, management, and outcomes were collected and baseline
      statistics performed. RESULTS: During the study 1076 women were seen. Most
      frequent hrHPV genotypes were: hrHPV other, 41%; and HPV16, 33%. The majority
      (72%) were found to have normal colposcopy; 28% had an abnormal colposcopic
      assessment (11% low-grade; 11% high-grade; 6% inadequate). The majority were
      discharged (83%) and only 5% underwent LLETZ. No cancers were detected. High
      grade cervical intraepithelial neoplasia (CIN) was found in 7%; overall risk of
      CIN2 was 1/29; 1/30 for CIN3. Presence of HPV16 was associated with a
      significantly higher risk of high-grade CIN; 1/9. CONCLUSION: This is the first
      study to report results for women referred to colposcopy with cytology negative,
      persistently positive hrHPV. Disease prevalence is low, although women with HPV16
      have a significantly higher likelihood of high-grade disease compared to other
      HPV subtypes.

PMID- 29350426
TI  - Efficacy of photodynamic therapy in the treatment of symptomatic oral lichen
      planus: A systematic review.
AB  - BACKGROUND: The aim of this study was to systematically review the efficacy of
      photodynamic therapy (PDT) in the management of symptomatic oral lichen planus
      (OLP). MATERIALS AND METHODS: PubMed/MEDLINE, Scopus, and ISI Web of knowledge
      were searched until July 2017, using the following keywords: OLP, erosive lichen
      planus, lichen planus, and PDT. RESULTS: Five clinical studies were included. The
      risk of bias was considered high in 4 studies and moderate in 1 study. The
      efficacy of PDT was compared with topical corticosteroids in all included
      studies. Laser wavelengths, duration of irradiation, and power density ranged
      between 420-660 nm, 30 seconds to 10 minutes, and 10-500 mW/cm2 , respectively.
      All studies reported PDT to be effective in the management of symptomatic OLP.
      Two studies reported PDT to be as effective as corticosteroids, 1 study reported
      a better efficacy of PDT compared to corticosteroids, whereas 2 studies found PDT
      to be inferior to corticosteroids. CONCLUSIONS: The limited available evidence
      suggests that PDT is an effective treatment option for the management of OLP.
      However, due to the limited number of studies included in this review and
      heterogeneity among these studies, more well-designed clinical trials with
      adequate sample sizes are highly warranted.

PMID- 29350425
TI  - The impact of preapheresis white blood cell count on autologous peripheral blood
      stem cell collection efficiency and HSC infusion side effect rate.
AB  - BACKGROUND: Autologous peripheral blood hematopoietic stem cell (PBSC) collection
      efficiency (CE) is reportedly affected by the patient's blood properties;
      however, studies to identify factors correlated with CE have shown inconsistent
      results. Additionally, variables such as stem cell graft granulocyte content and
      patient age, sex, and underlying disease, may be associated with hematopietic
      stem cell (HSC) infusion-related adverse reactions. In this study, we evaluated
      the correlation of preleukapheresis PB granulocyte count and PBSC harvest
      variables with CD34+ collection yield and efficiency, and thawed HSC infusion
      side effect occurrence. PATIENTS AND METHODS: We evaluated data from 361 patients
      who had undergone autologous PBSC transplant. Large volume leukapheresis was the
      method for PBSC collection. Complete Blood Count and CD34+ cell enumeration were
      performed in the preapheresis PB and the apheresis product sample. The PBSC
      grafts were submitted to non-controlled rate freezing after addition of 5% DMSO
      plus 6% hidroxyethylstarch as a cryoprotectant solution. The cryopreserved graft
      was thawed in a 37 degrees C water bath and then infused without further
      manipulation. RESULTS: The CD34+ yield was associated with preapheresis PB CD34+
      count and immature granulocyte count. The PBSC CE was negatively correlated with
      preapheresis white blood cell (WBC), immature granulocyte and granulocyte count.
      The leukapheresis product total nucleated cell (TNC) and granulocyte content was
      correlated with the thawed graft infusion side effect occurrence. CONCLUSION:
      This study has shown that preapheresis PB WBC and granulocyte counts were
      associated with leukapheresis CE. Additionally, the leukapheresis product TNC and
      granulocyte content was correlated with thawed graft infusion side effect
      occurrence.

PMID- 29350427
TI  - Role of microglia in the spinal cord in colon-to-bladder neural crosstalk in a
      rat model of colitis.
AB  - AIMS: We investigated whether spinal cord microglia are involved in colon-to
      bladder neural crosstalk in a rat model of colitis. METHODS: Adult female SD rats
      were divided into A) control, B) colitis, and C) colitis + minocycline groups.
      Experimental colitis was induced by administering 50% trinitrobenzene sulfonic
      acid into the distal colon in the colitis group and the minocycline group.
      Minocycline, a microglial inhibitor, was continuously infused into the
      intrathecal space in the minocycline group. The following investigations were
      performed on day 7: (1) continuous cystometry (CMG) in an awake condition; (2)
      nociceptive behavior observation induced by intravesical instillation of
      resiniferatoxin; (3) toluidine blue staining in the bladder; (4)
      Immunofluorescence staining for the microglial marker, CD11b, in L6 spinal cord
      sections; and (5) quantitative RT-PCR to investigate interleukin-1beta (IL
      1beta), chemokine ligand 3 (CCL3), and brain-derived neurotrophic factor (BDNF)
      gene expression in the L6 spinal cord. RESULTS: In comparison with the control
      group, the colitis group showed significant increases in (1) micturition
      frequency during cystometry; (2) resiniferatoxin-induced freezing behavior
      (bladder pain); (3) the number of total and degranulated mast cells in the
      bladder; (4) the number of microglia in the L6 spinal cord, and (5) the
      expression of IL-1beta, CCL3, and BDNF mRNA in the L6 spinal cord. Moreover,
      intrathecal administration of minocycline alleviated these pathophysiological
      findings caused by experimental colitis. CONCLUSIONS: Spinal microglia may play
      an important role in colitis-induced bladder overactivity and enhanced bladder
      pain sensitivity in colitis rats.

PMID- 29350428
TI  - Meta-analysis of fish early life stage tests-Association of toxic ratios and
      acute-to-chronic ratios with modes of action.
AB  - Fish early life stage (ELS) tests (Organisation for Economic Co-operation and
      Development test guideline 210) are widely conducted to estimate chronic fish
      toxicity. In these tests, fish are exposed from the embryonic to the juvenile
      life stages. To analyze whether certain modes of action are related to high toxic
      ratios (i.e., ratios between baseline toxicity and experimental effect) and/or
      acute-to-chronic ratios (ACRs) in the fish ELS test, effect concentrations (ECs)
      for 183 compounds were extracted from the US Environmental Protection Agency's
      ecotoxicity database. Analysis of ECs of narcotic compounds indicated that
      baseline toxicity could be observed in the fish ELS test at similar
      concentrations as in the acute fish toxicity test. All nonnarcotic modes of
      action were associated with higher toxic ratios, with median values ranging from
      4 to 9.3 * 104 (uncoupling < reactivity < neuromuscular toxicity < methemoglobin
      formation < endocrine disruption < extracellular matrix formation inhibition).
      Four modes of action were also found to be associated with high ACRs: 1) lysyl
      oxidase inhibition leading to notochord distortion, 2) putative methemoglobin
      formation or hemolytic anemia, 3) endocrine disruption, and 4) compounds with
      neuromuscular toxicity. For the prediction of ECs in the fish ELS test with
      alternative test systems, endpoints targeted to the modes of action of compounds
      with enhanced toxic ratios or ACRs could be used to trigger fish ELS tests or
      even replace these tests. Environ Toxicol Chem 2018;37:955-969. (c) 2018 SETAC.

PMID- 29350429
TI  - Sprint performance and propulsion asymmetries on an ergometer in trained high-
      and low-point wheelchair rugby players.
AB  - The purpose of this study was to examine the propulsion asymmetries of wheelchair
      athletes while sprinting on an instrumented, dual-roller ergometer system.
      Eighteen experienced wheelchair rugby players (8 low point (LP) (class <=1.5) and
      10 high point (HP) (class >=2.0)) performed a 15-second sprint in their sports
      wheelchair on the instrumented ergometer. Asymmetry was defined as the difference
      in distance and power output (PO) between left and right sides when the best side
      reached 28 m. Propulsion techniques were quantified based on torque and velocity
      data. HP players covered an average 3 m further than the LP players (P = .002)
      and achieved faster sprint times than LP players (6.95 +/- 0.89 vs 8.03 +/- 0.68
      seconds, P = .005) and at the time the best player finished (5.96 seconds).
      Higher peak POs (667 +/- 108 vs 357 +/- 78 W, P = .0001) and greater peak speeds
      that were also evident were for HP players (4.80 +/- 0.71 vs 4.09 +/- 0.45 m/s, P
      = .011). Greater asymmetries were found in HP players for distance (1.86 +/- 1.43
      vs 0.70 +/- 0.65 m, P = .016), absolute peak PO (P = .049), and speed (0.35 +/-
      0.25 vs 0.11 +/- 0.10 m/s, P = .009). Although HP players had faster sprint times
      over 28 m (achieved by a higher PO), high standard deviations show the
      heterogeneity within the two groups (eg, some LP players were better than HP
      players). Quantification of asymmetries is important not only for classifiers but
      also for sports practitioners wishing to improve performance as they could be
      addressed through training and/or wheelchair configuration.

PMID- 29350430
TI  - On the impact of sample size on median lethal concentration estimation in acute
      fish toxicity testing: Is n = 7/group enough?
AB  - The fish acute toxicity test method is foundational to aquatic toxicity testing
      strategies, yet the literature lacks a concise sample size assessment. Although
      various sources address sample size, historical precedent seems to play a larger
      role than objective measures. We present a novel and comprehensive quantification
      of the effect of sample size on estimation of the median lethal concentration
      (LC50), covering a wide range of scenarios. The results put into perspective the
      practical differences across a range of sample sizes, from n = 5/concentration up
      to n = 23/concentration. We also provide a framework for setting sample size
      guidance illustrating ways to quantify the performance of LC50 estimation, which
      can be used to set sample size guidance given reasonably difficult (or worst
      case) scenarios. There is a clear benefit to larger sample size studies: they
      reduce error in the determination of LC50s, and lead to more robust safe
      environmental concentration determinations, particularly in cases likely to be
      called worst-case (shallow slope and true LC50 near the edges of the
      concentration range). Given that the use of well-justified sample sizes is
      crucial to reducing uncertainty in toxicity estimates, these results lead us to
      recommend a reconsideration of the current de minimis 7/concentration sample size
      for critical studies (e.g., studies needed for a chemical registration, which are
      being tested for the first time, or involving difficult test substances). Environ
      Toxicol Chem 2018;37:1565-1578. (c) 2018 SETAC.

PMID- 29350431
TI  - miFAST: A novel and rapid microRNA target capture method.
AB  - MicroRNAs (miRNAs), small 22-25 nucleotide non-coding RNAs, play important roles
      in cellular and tumor biology. However, characterizing miRNA function remains
      challenging due to an abundance of predicted targets and an experimental
      bottleneck in identifying biologically relevant direct targets. Here, we
      developed a novel technique (miFAST) to identify direct miRNA target genes. Using
      miFAST, we confirmed several previously reported miR-340 target genes and
      identified five additional novel direct miR-340 targets in melanoma cells. This
      methodology can also be efficiently applied for the global characterization of
      miRNA targets. Utilizing miFAST to characterize direct miRNA targetomes will
      further our understanding of miRNA biology and function.

PMID- 29350432
TI  - National Public Health Data Systems in the United States: Applications to Child
      Agricultural Injury Surveillance.
AB  - PURPOSE: The United States has no comprehensive national surveillance system for
      fatal or nonfatal child agricultural injuries. Thus, important knowledge gaps
      exist about recurrent injury patterns that could provide targeted focus for
      prevention efforts. The purpose of this study was to explore existing US public
      health data systems to determine their utility with respect to informing child
      agricultural injury surveillance and primary prevention. METHODS: Public health
      data systems were selected if they: (1) were national in scope, (2) were active
      and ongoing, (3) included physical injuries, and (4) contained a "farm" location
      variable. Data systems explored included National Emergency Medical Services
      Information System, National Trauma Data Bank, National Electronic Injury
      Surveillance System-All Injury Program, and National Vital Statistics System
      Multiple Cause File. FINDINGS: Each data system contained substantial information
      per case with the number of fields ranging from 77 to 127. Beyond basic
      demographic information about the injured child, there were many injury
      descriptors, but few commonalities across systems. The most striking finding was
      the uniform absence of information on injury circumstances; that is, why and how
      the injury occurred, which is fundamental to planning and evaluating prevention
      initiatives. CONCLUSIONS: Although these public health data systems captured many
      details regarding medical aspects of the injury, they included little information
      on circumstances leading to injury, thus limiting their utility for child
      agricultural injury surveillance and primary prevention initiatives. We recommend
      any child agricultural injury data collection tool formally incorporate a
      structured narrative so underlying circumstances leading to injury events are
      documented.

PMID- 29350433
TI  - Amino group of salicylic acid exhibits enhanced inhibitory potential against
      insulin amyloid fibrillation with protective aptitude toward amyloid induced
      cytotoxicity.
AB  - Protein misfolding and aggregation lead to amyloid generation that in turn may
      induce cell membrane disruption and leads to cell apoptosis. In an effort to
      prevent or treat amyloidogenesis, large number of studies has been paying
      attention on breakthrough of amyloid inhibitors. In the present work, we aim to
      access the effect of two drugs, that is, acetylsalicylic acid and 5-amino
      salicylic acid on insulin amyloids by using various biophysical, imaging, cell
      viability assay, and computational approaches. We established that both drugs
      reduce the turbidity, light scattering and fluorescence intensity of amyloid
      indicator dye thioflavin T. Premixing of drugs with insulin inhibited the
      nucleation phase and inhibitory potential was boosted by increasing the
      concentration of the drug. Moreover, addition of drugs at the studied
      concentrations attenuated the insulin fibril induced cytotoxicity in breast
      cancer cell line MDA-MB-231. Our results highlight the amino group of salicylic
      acid exhibited enhanced inhibitory effects on insulin fibrillation in comparison
      to acetyl group. It may be due to presence of amino group that helps it to
      prolong the nucleation phase with strong binding as well as disruption of
      aromatic and hydrophobic stacking that plays a key role in amyloid progression.

PMID- 29350434
TI  - The cystine-glutamate exchanger (xCT, Slc7a11) is expressed in significant
      concentrations in a subpopulation of astrocytes in the mouse brain.
AB  - : The cystine-glutamate exchanger (xCT) promotes glutathione synthesis by
      catalyzing cystine uptake and glutamate release. The released glutamate may
      modulate normal neural signaling and contribute to excitotoxicity in pathological
      situations. Uncertainty, however, remains as neither the expression levels nor
      the distribution of xCT have been unambiguously determined. In fact, xCT has been
      reported in astrocytes, neurons, oligodendrocytes and microglia, but most of the
      information derives from cell cultures. Here, we show by immunohistochemistry and
      by Western blotting that xCT is widely expressed in the central nervous system of
      both sexes. The labeling specificity was validated using tissue from xCT knockout
      mice as controls. Astrocytes were selectively labeled, but showed greatly varying
      labeling intensities. This astroglial heterogeneity resulted in an astrocyte
      domain-like labeling pattern. Strong xCT labeling was also found in the
      leptomeninges, along some blood vessels, in selected circumventricular organs and
      in a subpopulation of tanycytes residing the lateral walls of the ventral third
      ventricle. Neurons, oligodendrocytes and resting microglia, as well as reactive
      microglia induced by glutamine synthetase deficiency, were unlabeled. The
      concentration of xCT protein in hippocampus was compared with that of the EAAT3
      glutamate transporter by immunoblotting using a chimeric xCT-EAAT3 protein to
      normalize xCT and EAAT3 labeling intensities. The immunoblots suggested an
      xCT/EAAT3 ratio close to one (0.75 +/- 0.07; average +/- SEM; n = 4) in adult
      C57BL6 mice. CONCLUSIONS: xCT is present in select blood/brain/CSF interface
      areas and in an astrocyte subpopulation, in sufficient quantities to support the
      notion that system xc- provides physiologically relevant transport activity.

PMID- 29350435
TI  - From micro- to macro-structures in multiple sclerosis: what is the added value of
      diffusion imaging.
AB  - Diffusion imaging has been instrumental in understanding damage to the central
      nervous system as a result of its sensitivity to microstructural changes.
      Clinical applications of diffusion imaging have grown exponentially over the past
      couple of decades in many neurological and neurodegenerative diseases, such as
      multiple sclerosis (MS). For several reasons, MS has been extensively researched
      using advanced neuroimaging techniques, which makes it an 'example disease' to
      illustrate the potential of diffusion imaging for clinical applications. In
      addition, MS pathology is characterized by several key processes competing with
      each other, such as inflammation, demyelination, remyelination, gliosis and
      axonal loss, enabling the specificity of diffusion to be challenged. In this
      review, we describe how diffusion imaging can be exploited to investigate micro-,
      meso- and macro-scale properties of the brain structure and discuss how they are
      affected by different pathological substrates. Conclusions from the literature
      are that larger studies are needed to confirm the exciting results from initial
      investigations before current trends in diffusion imaging can be translated to
      the neurology clinic. Also, for a comprehensive understanding of pathological
      processes, it is essential to take a multiple-level approach, in which
      information at the micro-, meso- and macroscopic scales is fully integrated.

PMID- 29350436
TI  - Age difference between parents influences parity and number of sons.
AB  - OBJECTIVES: Among couples, women usually prefer slightly older men, and men tend
      to choose much younger partners. Age difference between partners has been shown
      to influence their parity; however, results of previous studies are inconsistent.
      This study analyzed relationships between husband and wife age difference and
      their total number of children, and number of daughters and sons in a
      contemporary, rural Polish population. METHODS: Demographic and reproductive data
      were collected from 384 postmenopausal women from rural Poland who were married
      only once. Regression models were used to evaluate the impact of the age gap
      between partners on total number of children and on number of daughters and sons.
      Women's age, age at marriage (as an indicator of reproductive value), and years
      of education were used in analyzes as potential confounders. RESULTS: There was
      an inverted U-shape association between parental age difference and number of
      children and also the number of sons. The highest number of children and sons was
      observed when men were approximately 6.5 years older than their wives. There was
      no significant relationship between parental age difference and number of
      daughters. CONCLUSIONS: Age difference between partners is important for
      reproductive success (with younger wives having higher reproductive potential)
      and is also related to number of sons. Older husbands might provide more
      resources for the family, thus facilitating production of well-nourished male
      offspring. Future research should evaluate not only number of children but also
      their biological condition, health, and lifetime achievements in relation to the
      age difference between their parents.

PMID- 29350437
TI  - Diffusion tensor imaging MRI of sickle cell kidney disease: initial results and
      comparison with iron deposition.
AB  - Chronic kidney disease (CKD) occurs in over one-third of patients with sickle
      cell disease (SCD) and can progress to end-stage renal disease. Unfortunately,
      current clinical assessments of kidney function are insensitive to early-stage
      CKD. Previous studies have shown that diffusion magnetic resonance imaging (MRI)
      can sensitively detect regional renal microstructural changes associated with
      early-stage CKD. However, previous MRI studies in patients with SCD have been
      largely limited to the detection of renal iron deposition assessed by T2 *
      relaxometry. In this pilot imaging study, we compare MRI assessments of renal
      microstructure (diffusion) and iron deposition (T2 *) in patients with SCD and in
      non-SCD control subjects. Diffusion tensor imaging (DTI) and T2 * relaxometry MRI
      data were obtained for pediatric (n = 5) and adult (n = 4) patients with SCD, as
      well as for non-SCD control subjects (n = 10), on a Siemens Espree 1.5-T MRI
      scanner. A region-of-interest analysis was used to calculate mean medullary and
      cortical values for each MRI metric. MRI findings were also compared with
      clinical assessments of renal function and hemolysis. Patients with SCD showed a
      significant decrease in medullary fractional anisotropy (FA, p = 0.0001) in
      comparison with non-SCD subjects, indicative of microstructural alterations in
      the renal medulla of patients with SCD. Cortical and medullary reductions in T2 *
      (increased iron deposition, p = <=0.0001) were also observed. Significant
      correlations were also observed between kidney T2 * assessments and multiple
      measures of hemolysis. This is the first DTI MRI study of patients with SCD to
      demonstrate reductions in medullary FA despite no overt CKD [estimated glomerular
      filtration rate (eGFR) > 100 mL/min/1.73 m2 ]. These medullary FA changes are
      consistent with previous studies in patients with CKD, and suggest that DTI MRI
      can provide a useful measure of kidney injury to complement MRI assessments of
      iron deposition.

PMID- 29350439
TI  - Tandem mass spectroscopy as a tool for investigation of complexes of PNP-lariat
      ether derivative with metal ions.
AB  - The novel PNP-lariat ether L with cyclotriphosphazene ring incorporated in the
      macrocyclic structure was synthesized and checked by the electrospray mass
      spectrometry (ESI-MS) method for the ability to bind different types of ions Ag+
      , Ca2+ , Cd2+ , Cu2+ , and Pb2+ . Furthermore, the stability constants of the
      abovementioned ion complexes with the investigated ligand have been determined by
      direct and competitive potentiometric methods. To evaluate the stability of
      various complex types and to confirm the way of metal cation binding, the tandem
      mass spectra of the investigated ligand and its complexes were taken. As a
      result, we obtained quite a good relationship between the number and main types
      of complex species observed in ESI-MS experiments and the forms of complexes for
      which the stabilization constants were determined by potentiometric methods.
      Moreover, we also concluded that in case of big discrepancies of stability
      constants, ESI-MS experiments could provide information about the most stable
      form of the complexes, but they fail when the differences between the strength of
      the coordination binding are slightly different.

PMID- 29350438
TI  - Astrocytic glutamine synthetase is expressed in the neuronal somatic layers and
      down-regulated proportionally to neuronal loss in the human epileptic
      hippocampus.
AB  - Human mesial temporal lobe epilepsy (MTLE) features subregion-specific
      hippocampal neurodegeneration and reactive astrogliosis, including up-regulation
      of the glial fibrillary acidic protein (GFAP) and down-regulation of glutamine
      synthetase (GS). However, the regional astrocytic expression pattern of GFAP and
      GS upon MTLE-associated neurodegeneration still remains elusive. We assessed GFAP
      and GS expression in strict correlation with the local neuronal number in
      cortical and hippocampal surgical specimens from 16 MTLE patients using
      immunohistochemistry, stereology and high-resolution image analysis for digital
      pathology and whole-slide imaging. In the cortex, GS-positive (GS+) astrocytes
      are dominant in all neuronal layers, with a neuron to GS+ cell ratio of 2:1. GFAP
      positive (GFAP+) cells are widely spaced, with a GS+ to GFAP+ cell ratio of 3:1
      5:1. White matter astrocytes, on the contrary, express mainly GFAP and, to a
      lesser extent, GS. In the hippocampus, the neuron to GS+ cell ratio is
      approximately 1:1. Hippocampal degeneration is associated with a reduction of GS+
      astrocytes, which is proportional to the degree of neuronal loss and primarily
      present in the hilus. Up-regulation of GFAP as a classical hallmark of reactive
      astrogliosis does not follow the GS-pattern and is prominent in the CA1. Reactive
      alterations were proportional to the neuronal loss in the neuronal somatic layers
      (stratum pyramidale and hilus), while observed to a lesser extent in the
      axonal/dendritic layers (stratum radiatum, molecular layer). We conclude that
      astrocytic GS is expressed in the neuronal somatic layers and, upon
      neurodegeneration, is down-regulated proportionally to the degree of neuronal
      loss.

PMID- 29350440
TI  - Abrupt burial imparts persistent changes to the bacterial diversity of turbidite
      associated sediment profiles.
AB  - The emplacement of subaqueous gravity-driven sediment flows imposes a significant
      physical and geochemical impact on underlying sediment and microbial communities.
      Although previous studies have established lasting mineralogical and biological
      signatures of turbidite deposition, the response of bacteria and archaea within
      and beneath debris flows remains poorly constrained. Both bacterial cells
      associated with the underlying sediment and those attached to allochthonous
      material must respond to substantially altered environmental conditions and
      selective pressures. As a consequence, turbidites and underlying sediments
      provide an exceptional opportunity to examine (i) the microbial community
      response to rapid sedimentation and (ii) the preservation and identification of
      displaced micro-organisms. We collected Illumina MiSeq sequence libraries across
      turbidite boundaries at ~26 cm sediment depth in La Jolla Canyon off the coast of
      California, and at ~50 cm depth in meromictic Twin Lake, Hennepin County, MN. 16S
      rRNA gene signatures of relict and active bacterial populations exhibit
      persistent differences attributable to turbidite deposition. In particular, both
      the marine and lacustrine turbidite boundaries are sharply demarcated by the
      abundance and diversity of Chloroflexi, suggesting a characteristic sensitivity
      to sediment disturbance history or to differences in organic substrates across
      turbidite profiles. Variations in the abundance of putative dissimilatory sulfate
      reducing Deltaproteobacteria across the buried La Jolla Canyon sediment-water
      interface reflect turbidite-induced changes to the geochemical environment.
      Species-level distinctions within the Deltaproteobacteria clearly conform to the
      sedimentological boundary, suggesting a continuing impact of genetic inheritance
      distinguishable from broader trends attributable to selective pressure. Abrupt,
      <1-cm scale changes in bacterial diversity across the Twin Lake turbidite contact
      are consistent with previous studies showing that relict DNA signatures
      attributable to sediment transport may be more easily preserved in low-energy,
      anoxic environments. This work raises the possibility that deep subsurface
      microbial communities may inherit variations in microbial diversity from sediment
      flow and deformation events.

PMID- 29350441
TI  - Ultrasensitive detection of Shiga toxin 2 and its variants in Shiga toxin
      producing Escherichia coli strains by a time-resolved fluorescence immunoassay.
AB  - A rapid and sensitive two-step time-resolved fluorescence immunoassay (TRFIA) was
      developed for the detection of Shiga toxin 2 (Stx2) and its variants in Shiga
      toxin-producing Escherichia coli (STEC) strains. In sandwich mode, a monoclonal
      antibody against Stx2 was coated on a microtiter plate as a capture antibody. A
      tracer antibody against Stx2 labeled with europium(III) (Eu3+ ) chelate was then
      used as a detector, followed by fluorescence measurements using time-resolved
      fluorescence. The sensitivity of Stx2 detection was 0.038 ng/ml (dynamic range,
      0.1-1000 ng/ml). The intra- and inter-assay coefficients of variation of the
      assay were 3.2% and 3.6%, respectively. The performance of the established assay
      was evaluated using culture supernatants of STEC strains, and the results were
      compared to those of a common HRP (horseradish peroxidase) labeling immunosorbent
      assay. A polymerase chain reaction (PCR) for the detection of genes encoding Stx1
      and Stx2 was used as the reference for comparison. Correlation between the Stx2
      specific TRFIA and PCR was calculated by the use of kappa statics, exhibiting a
      perfect level of agreement. The availability of the sensitive and reliable Stx2
      specific TRFIA method for quantifying Stx2 and its variants in STEC strains will
      complement bacteria isolation-based platform and aid in the accurate and prompt
      diagnosis of STEC infections.

PMID- 29350443
TI  - Cutting reduces variation in biomass production of forage crops and allows low
      performers to catch up: A case study of Trifolium pratense L. (red clover).
AB  - Re-growth of fodder plants after grazing and mowing drives the profitability of
      their cultivation and is therefore an important target trait for plant breeding
      and agricultural engineering. However, for some fodder plants little is known
      about their re-growth dynamics in response to grazing or mowing. We analysed the
      native response of plant architecture, leaf morphology and growth performance to
      experimental cutting in wild Trifolium pratense L. (red clover) plants. A total
      of 150 potted clover plants were established under controlled field conditions,
      and half of the plants were cut to 5 cm 3 months after sowing. Each plant was
      measured every week for 5 months. The cut and subsequently re-grown plants
      carried fewer main branches (-20%), as well as fewer (-13%) and smaller (-32%)
      leaves than the control plants. However, the cut plants produced an average of
      17% more accumulated leaf area (cut + re-grown leaf area) than the control
      plants. This discrepancy was explained by variation in the growth strategy of the
      plants, where the cut plants invariably expressed a second growth phase, while
      almost half of the untreated plants did not. Our results suggest that cutting
      acted as an artificial trigger initiating a second growth phase in the cut plants
      and thereby contributed to yield increase. Exploiting this mechanism may set new
      goals for breeding and optimisation of the mowing regime.

PMID- 29350442
TI  - Role of ethylene and related gene expression in the interaction between
      strawberry plants and the plant growth-promoting bacterium Azospirillum
      brasilense.
AB  - Induced systemic resistance (ISR) is one of the indirect mechanisms of growth
      promotion exerted by plant growth-promoting bacteria, and can be mediated by
      ethylene (ET). We assessed ET production and the expression of related genes in
      the Azospirillum-strawberry plant interaction. Ethylene production was evaluated
      by gas chromatography in plants inoculated or not with A. brasilense REC3. Also,
      plants were treated with AgNO3 , an inhibitor of ET biosynthesis; with 1
      aminocyclopropane-1-carboxylic acid (ACC), a precursor of ET biosynthesis; and
      with indole acetic acid (IAA). Plant dry biomass and the growth index were
      determined to assess the growth-promoting effect of A. brasilense REC3 in
      strawberry plants. Quantitative real time PCR (qRT-PCR) was performed to analyse
      relative expression of the genes Faetr1, Faers1 and Faein4, which encode ET
      receptors; Factr1 and Faein2, involved in the ET signalling pathway; Faacs1
      encoding ACC synthase; Faaco1 encoding ACC oxidase; and Faaux1 and Faami1 for IAA
      synthesis enzymes. Results showed that ET acts as a rapid and transient signal in
      the first 12 h post-treatment. A. brasilense REC3-inoculated plants had a
      significantly higher growth index compared to control plants. Modulation of the
      genes Faetr1, Faers1, Faein4, Factr1, Faein2 and Faaco1 indicated activation of
      ET synthesis and signalling pathways. The up-regulation of Faaux1 and Faami1
      involved in IAA synthesis suggested that inoculation with A. brasilense REC3
      induces production of this auxin, modulating ET signalling. Ethylene production
      and up-regulation of genes associated with ET signalling in strawberry plants
      inoculated with A. brasilense REC3 support the priming activation characteristic
      of ISR. This type of resistance and the activation of systemic acquired
      resistance previously observed in this interaction indicate that both are present
      in strawberry plants, could act synergistically and increase protection against
      pathogens.

PMID- 29350444
TI  - Four cases of iridociliary tumors in domestic rabbits (Oryctolagus Cuniculus).
AB  - Spontaneously occurring ocular neoplasia is rarely reported in rabbits. This case
      series presents four cases of rabbits diagnosed with iridociliary tumors, which
      have not been previously reported in this species. Major pathological findings
      include epithelial tumors affecting the anterior uvea with variable pigmentation
      and basement membrane formation. Follow-up information was only available for two
      cases, but neither showed evidence of metastasis, suggesting that the prognosis
      for these tumors in rabbits, as in other species, may be very good.

PMID- 29350445
TI  - Application of computer-aided sperm analysis (CASA) for detecting sperm
      immobilizing antibody.
AB  - PROBLEM: Since the 1970s, anti-sperm antibodies have been studied as a pathogenic
      factor contributing to infertility. The complement-dependent sperm-immobilization
      test (SIT) and quantitative SIT have been used as effective tools for detecting
      anti-sperm antibodies in clinical settings. These tests have been carried out
      traditionally by manually counting the number of motile sperm through eye
      estimation. METHOD OF STUDY: In this study, we developed a novel method using
      computer-aided sperm analysis. The results were compared with those obtained by
      the traditional method. RESULTS: The results were identical and 25 of 78 samples
      tested were positive and 53 samples were negative for sperm-immobilizing (SI)
      antibodies based on both methods. For SI-positive samples, the values of SI50
      obtained using the two methods correlated closely with high co-efficiency.
      CONCLUSION: Using the novel method, manually counting the number of motile
      spermatozoa becomes unnecessary. The novel method presented here will increase
      the objectivity and convenience of using the SIT as a clinical indicator.

PMID- 29350446
TI  - Differential gene expression in trigeminal ganglia of male and female rats
      following chronic constriction of the infraorbital nerve.
AB  - BACKGROUND: The mechanisms underlying sex-based differences in pain and analgesia
      are poorly understood. In this study, we investigated gene expression changes in
      trigeminal ganglia (TG) of male and female rats exposed to infraorbital nerve
      chronic constriction injury (IoN-CCI). METHODS: Somatosensory assessments were
      performed prior to IoN-CCI and at selected time points postsurgery. Selected gene
      expression changes were examined with real-time quantitative polymerase chain
      reaction (RT-PCR) in ipsilateral TG at 21 days postsurgery. RESULTS: Rats exposed
      to IoN-CCI developed significant mechanical allodynia and hyperalgesia on days 19
      and 21 postsurgery. During this period, females developed significantly more
      allodynia but not hyperalgesia compared to males. At 21 days postsurgery,
      expression levels of 44 of the 84 investigated pain-related genes in ipsilateral
      TG were significantly regulated relative to naive rats in either sex. Csf1 and
      Cx3cr1 were up-regulated in both sexes, but the magnitude of regulation was
      significantly higher in females (p = 0.02 and p = 0.001, respectively). Htr1a and
      Scn9a were down-regulated in both sexes, but the down-regulation was
      significantly more pronounced in males (p = 0.04 and p = 0.02, respectively).
      Additionally, Cck, Il1a, Pla2g1b and Tnf genes were significantly regulated in
      females but not in males, and Chrna4 gene was significantly down-regulated in
      males but not in females. CONCLUSIONS: Our findings suggest sex-dependent gene
      regulation in response to nerve injury, which may contribute to sex dimorphism of
      trigeminal neuropathic pain. Further studies are needed to establish gene
      expression changes over time and correlate these with hormonal and other
      physiological parameters in male and female. SIGNIFICANCE: We present novel sex
      specific transcriptional regulation in trigeminal ganglia that may contribute to
      male-/female-based differences in trigeminal neuropathic pain. These findings are
      expected to open new research horizons, particularly in male versus female
      targeted therapeutic regimens.

PMID- 29350447
TI  - Effect of sedation with butorphanol on variables pertaining to the ophthalmic
      examination in dogs.
AB  - OBJECTIVE: To evaluate whether sedation with intramuscular butorphanol can
      interfere with different variables of the ocular examination in dogs. ANIMALS:
      Twenty-two beagles without ophthalmic abnormalities. PROCEDURES: Each dog was
      examined 20 min prior to and again just before administration of butorphanol to
      establish baseline data. The globe and nictitating membrane position was
      evaluated, and the following were recorded: menace response, dazzle reflex,
      corneal blink reflex, phenol red thread tear test (PRT), Schirmer tear test-1
      (STT-1), pupil size (PS) measurement, and rebound tonometry. Then, butorphanol
      was injected intramuscularly at a dose of 0.2 mg/kg and these procedures were
      repeated 10, 20, 30, and 45 min postadministration. A sedation score graded 0 to
      3 was also established at these time points. Statistical analyses were performed
      on quantitative data using ANOVA. RESULTS: The sedative effect was not associated
      with any changes in globe and nictitating membrane position; did not affect the
      results of the menace response, dazzle reflex, and corneal blink reflex; and had
      no significant effect on PRT values. However, butorphanol administration was
      associated with a statistically significant decrease in STT-1 and PS values (P <
      0.005), and a statistically significant increase in IOP (P < 0.05). All these
      variations remained in the range of normal values. CONCLUSIONS AND CLINICAL
      RELEVANCE: Butorphanol administered intramuscularly at 0.2 mg/kg provided a
      degree of sedation allowing eye examination, but was found to interfere with STT
      1, PS, and IOP values among the diagnostic tests studied. However, these values
      remained within normal limits.

PMID- 29350448
TI  - Clinical and genetic associations for carboplatin-related ototoxicity in children
      treated for retinoblastoma: A retrospective noncomparative single-institute
      experience.
AB  - BACKGROUND: Children with retinoblastoma treated with carboplatin chemotherapy
      risk moderate to severe, irreversible hearing loss. Based on published evidence,
      we hypothesized that ototoxicity risk is associated with clinical parameters and
      variants in candidate genes in drug metabolism pathways (methyltransferases
      [thiopurine S-methyltransferase, TPMT] and [catechol-O-methyltransferase, COMT],
      and drug transporter ABCC3). PROCEDURE: We retrospectively reviewed clinical
      records of patients with retinoblastoma treated with carboplatin chemotherapy
      regarding age (at diagnosis and chemotherapy initiation), chemotherapy sessions
      (cycles number, drug doses, and cumulative carboplatin dose), and hearing loss
      (defined as ototoxicity >=grade 2 by at least one classification system). Blood
      samples were genotyped for genetic variants in TPMT (rs12201199, rs1800460), COMT
      (rs4646316, rs9332377), and ABCC3 (rs1051640) by quantitative PCR and confirmed
      by allele-specific PCR. Univariate statistical tests, receiver-operating
      characteristic analysis, and Kaplan-Meier curves were used to examine the
      association between hearing loss, clinical factors, and variants in candidate
      genes. RESULTS: Audiometric data and stored DNA were available for 71 patients
      with retinoblastoma (88% carried an RB1 pathogenic variant allele). Median
      carboplatin cumulative dose was 1,400 mg/m2 (260-5,148 mg/m2 ). Ototoxicity
      occurred in 18 patients (25%), strongly associated with age at diagnosis (P =
      0.01) and age at chemotherapy initiation (OR = 4.99, P = 0.008). The highest
      likelihood ratio of hearing loss was associated with chemotherapy initiation
      <4.25 months of age. Ototoxicity was not associated with any tested genetic
      variants. CONCLUSIONS: We observed a 25% prevalence of ototoxicity in patients
      with retinoblastoma treated with carboplatin, higher than previously published.
      Age at chemotherapy initiation was associated with carboplatin-induced
      ototoxicity, with children <4.25 months of age at highest risk.

PMID- 29350449
TI  - Lipoidal corneal degeneration in aged falcons.
AB  - OBJECTIVE: To present a case series of idiopathic lipoidal corneal degeneration
      in falcons. ANIMALS STUDIED: Five falcons including three peregrine falcons
      (Falco peregrinus), one prairie falcon (Falco mexicanus), and one red-naped
      shaheen (Falco peregrinus babylonicus) were observed to develop slowly
      progressive corneal opacification that began at the temporal limbus and extended
      centripetally across the cornea over a period of years. Four of the birds were
      over 20 years old. PROCEDURES: All animals underwent complete ophthalmic
      examinations. A red-naped shaheen underwent ocular imaging via spectral-domain
      optical coherence tomography. Two peregrine falcons were euthanized due to
      declining health, and their eyes were examined histologically. RESULTS: The
      opacities were pale and granular, with frequent vascularization associated
      perilimbally. Diffuse neutral lipid was observed in stromal cells throughout the
      corneal stroma of both clear and opaque areas of the cornea, sparing only the
      acellular anterior limiting lamina. Clusters of cholesterol crystals surrounded
      by macrophages were present in the mid-stroma. Fibrosis was evident in a
      subepithelial location, which separated the epithelium from the anterior limiting
      lamina. Ultrastructurally, diffuse vacuolization of the keratocytes was observed.
      No other ophthalmic or systemic abnormalities were noted. CONCLUSIONS: Results
      suggest that lipid degeneration occurs rarely in captive falcons of advanced age.
      The underlying cause is unclear. Though unsubstantiated, possible contributing
      factors include dyslipoproteinemia, corneal trauma, diet, and age-related
      alterations in corneal metabolism. The initiation of pathology at the temporal
      limbus, as well as slow progression, suggests that exposure contributes to the
      onset and progression of this unique keratopathy.

PMID- 29350450
TI  - Cross-sectional and longitudinal analysis of nutritional status of school
      children from Bumbire Island (United Republic of Tanzania).
AB  - OBJECTIVE: To analyze the nutritional status of schoolchildren from Bumbire
      Island (Tanzania) from cross-sectional and longitudinal perspectives. METHODS:
      During 2014 and 2015, we collected anthropometric measurements in a sample of 437
      schoolchildren (226 males, 211 females; 5-16 years). A sub-sample of 126 children
      were measured in both surveys. Socio-demographic data have been taken and dietary
      habits investigated. The accuracy of age data was checked. Malnutrition
      prevalence was calculated according to the WHO references and the z-score
      criteria. RESULTS: The prevalence of undernutrition was high (stunting: 30.7%;
      underweight: 12.9%; thinness: 4.5%), while overweight was rare (2.4%). The
      prevalence of stunting was higher in males and in older children. The one-year
      longitudinal analysis indicated that stunting prevalence increased. CONCLUSIONS:
      Undernutrition is affecting Bumbire Island children, likely due to micronutrient
      deficiencies. The effects of linear growth deficit continue to accumulate
      throughout childhood and adolescent years.

PMID- 29350451
TI  - Morphological specializations of the epidermis of an angler catfish Chaca chaca
      (Siluriformes, Chacidae) in relation to its ecological niche: A scanning electron
      microscopic investigation.
AB  - The present work was undertaken with the aim to deduce morphological adaptations
      in skin of an angler catfish Chaca chaca by means of scanning electron
      microscopy. The fish is nocturnal, bottom dwelling, sluggish, ambush predator,
      lives in sand, mud, or soft substrates often buried and camouflaged for
      protection and to feed. The surface of the epidermis is covered with polygonal
      epithelial cells, each having surface relief of microridges forming intricate
      patterns. In between epithelial cells irregularly distributed mucous cell
      openings, randomly distributed epidermal specialized structures, taste buds, and
      neuromasts are discernible. The epidermal specialized structures are keratinized.
      These are either irregularly the rounded elevated plaque like or the cone shaped
      structures. The superficial keratinized cells could frequently be discernible
      exfoliated at the surface. At intervals, characteristic epidermal projections
      could be observed. Surface of these projections at intervals is differentiated
      into short stumpy protuberances, each bearing a taste bud at its summit. Further,
      near the basal portion of these epidermal projections, conical, or rounded plaque
      like epidermal specialized structures are also discernible. The surface sculpture
      of the skin of Chaca chaca is associated with the structural and functional
      significance and physiological adaptations of the epidermis with respect to its
      ecological niche.

PMID- 29350452
TI  - Anatomical and phenological implications of the relationship between Schinus
      polygama (Cav.) (Cabrera) and the galling insect Calophya rubra (Blanchard).
AB  - The success of galling insects could be determined by synchronisation with host
      plant phenology and climate conditions, ensuring suitable oviposition sites for
      gall induction and food resources for their survival. The anatomical,
      histochemical and phenological synchronisation strategies between Calophya rubra
      (Blanchard) (Hemiptera: Psylloidea) and its host, the evergreen plant Schinus
      polygama (Cav.) (Cabrera) (Anacardiaceae), in the Mediterranean climate of
      southern Chile was evaluated and compared to that of the congeneric C. cf.
      duvauae (Scott) from Brazil and closely related host plant S. engleri in a
      subtropical climate. Anatomical, histometric, histochemical and vegetative
      phenology studies of the stem and galls were conducted from June 2015 to December
      2016. Based on the anatomical, histometric and histochemical analysis, the
      conical stem gall traits imply gains over the non-galled stem toward the galling
      insect survival, but the maintenance of phellem, secretory ducts and pith
      indicate conservative developmental traits that cannot be manipulated by C.
      rubra. Our results indicate that the conditions of the Mediterranean climate zone
      limit C. rubra immature activity during unfavourable periods, probably
      determining a diapause period and a univoltine life cycle, which are
      peculiarities of the S. polygama- C. rubra system. The synchronisation between
      development and seasonality confers peculiarities to the S. polygama- C. rubra
      system in the Mediterranean climate zone.

PMID- 29350453
TI  - Late Cretaceous marine arthropods relied on terrestrial organic matter as a food
      source: Geochemical evidence from the Coon Creek Lagerstatte in the Mississippi
      Embayment.
AB  - The Upper Cretaceous Coon Creek Lagerstatte of Tennessee, USA, is known for its
      extremely well-preserved mollusks and decapod crustaceans. However, the
      depositional environment of this unit, particularly its distance to the
      shoreline, has long been equivocal. To better constrain the coastal proximity of
      the Coon Creek Formation, we carried out a multiproxy geochemical analysis of
      fossil decapod (crab, mud shrimp) cuticle and associated sediment from the type
      section. Elemental analysis and Raman spectroscopy confirmed the presence of
      kerogenized carbon in the crabs and mud shrimp; carbon isotope (delta13 C)
      analysis of bulk decapod cuticle yielded similar mean delta13 C values for both
      taxa (-25.10/00 and -260/00, respectively). Sedimentary biomarkers were composed
      of n-alkanes from C16 to C36 , with the short-chain n-alkanes dominating, as well
      as other biomarkers (pristane, phytane, hopanes). Raman spectra and biomarker
      thermal maturity indices suggest that the Coon Creek Formation sediments are
      immature, which supports retention of unaltered, biogenic isotopic signals in the
      fossil organic carbon remains. Using our isotopic results and published calcium
      carbonate delta13 C values, we modeled carbon isotope values of carbon sources in
      the Coon Creek Formation, including potential marine (phytoplankton) and
      terrestrial (plant) dietary sources. Coon Creek Formation decapod delta13 C
      values fall closer to those estimated for terrigenous plants than marine
      phytoplankton, indicating that these organisms were feeding primarily on
      terrigenous organic matter. From this model, we infer that the Coon Creek
      Formation experienced significant terrigenous organic matter input via a
      freshwater source and thus was deposited in a shallow, nearshore marine
      environment proximal to the shoreline. This study helps refine the paleoecology
      of nearshore settings in the Mississippi Embayment during the global climatic
      shift in the late Campanian-early Maastrichtian and demonstrates for the first
      time that organic delta13 C signatures in exceptionally preserved fossil marine
      arthropods are a viable proxy for use in paleoenvironmental reconstructions.

PMID- 29350454
TI  - Patterns of Internet-based health information seeking in adult survivors of
      childhood cancer.
AB  - BACKGROUND: To assess where, when, and why survivors of childhood cancer seek
      health information. PROCEDURE: Data from the Childhood Cancer Survivor Study
      (CCSS) cohort (n = 1386) and Health Information National Trends Survey (n = 2385)
      were analyzed to determine the health information seeking strategies of childhood
      cancer survivors. Descriptive frequencies, chi2 analyses, t-tests, and
      multivariable logistic regression models were used. RESULTS: To seek health
      related information for themselves, 54% (n = 742) of the childhood survivors
      reported using the Internet in the past 12 months, compared to 45% of the general
      population (adjusted OR: 2.76; 95% CI: 2.40-3.19). Childhood cancer survivors who
      used the Internet for health information were more likely to be female, between
      the ages of 18-34, have received some college education or be a college graduate,
      and report being in poor health. Although survivors were less likely than the
      general population to trust health information from the Internet (P < 0.01), they
      indicated that they would like a secure website that uses information from their
      medical records to provide individualized health-related information. CONCLUSION:
      The use of the Internet to access health information among the childhood cancer
      survivors was over 50%. Information on late effects was a high priority for most
      survivors, as was their interest in websites related to late effects and a
      website on patient information tailored to personal situations. Identification of
      factors associated with searching the Internet for cancer information may provide
      direction for development of effective cancer communication interventions for
      this at-risk population.

PMID- 29350455
TI  - A novel prognostic six-CpG signature in glioblastomas.
AB  - AIMS: We aimed to identify a clinically useful biomarker using DNA methylation
      based information to optimize individual treatment of patients with glioblastoma
      (GBM). METHODS: A six-CpG panel was identified by incorporating genome-wide DNA
      methylation data and clinical information of three distinct discovery sets and
      was combined using a risk-score model. Different validation sets of GBMs and
      lower-grade gliomas and different statistical methods were implemented for
      prognostic evaluation. An integrative analysis of multidimensional TCGA data was
      performed to molecularly characterize different risk tumors. RESULTS: The six-CpG
      risk-score signature robustly predicted overall survival (OS) in all discovery
      and validation cohorts and in a treatment-independent manner. It also predicted
      progression-free survival (PFS) in available patients. The multimarker epigenetic
      signature was demonstrated as an independent prognosticator and had better
      performance than known molecular indicators such as glioma-CpG island methylator
      phenotype (G-CIMP) and proneural subtype. The defined risk subgroups were
      molecularly distinct; high-risk tumors were biologically more aggressive with
      concordant activation of proangiogenic signaling at multimolecular levels.
      Accordingly, we observed better OS benefits of bevacizumab-contained therapy to
      high-risk patients in independent sets, supporting its implication in guiding
      usage of antiangiogenic therapy. Finally, the six-CpG signature refined the risk
      classification based on G-CIMP and MGMT methylation status. CONCLUSIONS: The
      novel six-CpG signature is a robust and independent prognostic indicator for GBMs
      and is of promising value to improve personalized management.

PMID- 29350456
TI  - A prospective study of family predictors of health-related quality of life in
      pediatric brain tumor survivors.
AB  - BACKGROUND: The objective of this study was to examine prospectively the
      associations between family functioning at the end of tumor-directed treatment
      and the health-related quality of life (HRQL) of pediatric brain tumor survivors
      (PBTSs) approximately 9 months later. PROCEDURE: Thirty-five PBTS (age 6-16
      years) and their mothers completed measures of family functioning and survivor
      HRQL within 5 months of completing tumor-directed therapy (baseline) and again
      approximately 9 months later (follow-up). RESULTS: Survivor-rated general family
      functioning at baseline significantly predicted mother proxy- and self-reported
      survivor HRQL at follow-up when controlling for survivor HRQL at baseline and
      relevant demographic and treatment-related variables. CONCLUSIONS: Family
      functioning is a key factor contributing to survivor HRQL and should be screened
      throughout the course of tumor-directed treatment. Psychosocial interventions
      directed toward improving general family functioning may improve survivor well
      being following the completion of treatment.

PMID- 29350457
TI  - Improved outcome at end of treatment in the collaborative Wilms tumour Africa
      project.
AB  - BACKGROUND: The Collaborative Wilms Tumour (WT) Africa Project has implemented an
      adapted WT treatment guideline in sub-Saharan Africa as a multi-centre
      prospective clinical trial. A retrospective, baseline evaluation of end-of
      treatment outcome was performed for a 2-year period prior to the introduction of
      this guideline. The collaborative project aims to reduce both treatment
      abandonment and death during treatment to less than 10% for improving survival.
      PROCEDURE: All participating centres obtained local Institutional Research Board
      (IRB) approval and implemented the adapted WT treatment guideline. End-of
      treatment outcome was documented for 2 years. It was divided into alive without
      evidence of disease, treatment abandonment, death during treatment and persistent
      disease. The outcome of children enroled in the first 2 years of the prospective
      clinical trial has been compared to the outcome before the start of the project.
      RESULTS: One hundred twenty-two patients were included in the baseline evaluation
      (2011-2012) and 133 in the first 2 years of the collaborative clinical trial
      (2014-2015). The percentage of patients alive without evidence of disease at the
      end of treatment increased from 52% (63/122) to 68% (90/133; P = 0.01). Treatment
      abandonment decreased from 23% (28/122) to 13% (17/133; P = 0.03). Death during
      treatment decreased from 21% (26/122) to 13% (17/133; P = 0.07). CONCLUSION: This
      collaboration, using relatively simple and low-cost interventions, led to a
      significant decrease in treatment abandonment and increase in survival without
      evidence of disease at the end of treatment.

PMID- 29350458
TI  - Der-Cherng Liang, MD, 1947-2017.

PMID- 29350459
TI  - NOURISH-T: Targeting caregivers to improve health behaviors in pediatric cancer
      survivors with obesity.
AB  - BACKGROUND: Obesity rates in pediatric cancer survivors (PCS) are alarmingly
      high. Although healthy lifestyle changes may prevent future health complications,
      promoting healthy behaviors in PCS is challenging, and few interventions have
      successfully addressed this issue. PROCEDURE: This randomized control trial
      evaluated the feasibility and preliminary effectiveness of a parent-focused six
      session intervention, NOURISH-T (Nourishing Our Understanding of Role Modeling to
      Improve Support and Health for Healthy Transitions), compared with enhanced usual
      care (EUC) on the outcomes of caregiver and PCS anthropometric measurements,
      eating behaviors, and physical activity. Behavioral and self-report assessments
      of caregivers and PCS in both conditions were conducted at baseline,
      postintervention, and at a 4-month follow-up. RESULTS: In comparison to no change
      among EUC caregivers, NOURISH-T caregivers showed small yet significant decreases
      from baseline through follow-up on BMI, waist-hip ratio, and total daily caloric
      intake. However, there was no change with regard to daily fat and sugar intake.
      NOURISH-T caregivers also showed positive changes in their child feeding
      behaviors, including decreases in pressuring their child to eat and restricting
      their child's eating and increased eating together as a family. Similarly,
      decreases in BMI percentile, waist-hip ratio, and sugary beverage consumption
      were found for NOURISH-T PCS from baseline to postintervention. NOURISH-T PCS
      also significantly increased their daily steps, whereas EUC PCS decreased their
      daily steps. CONCLUSIONS: Results suggest that an intervention targeting parents
      is feasible and demonstrates preliminary effectiveness. NOURISH-T showed a longer
      term effect on caregivers, and, although shorter term effect, a positive impact
      on the PCS themselves. Implications for ways to improve NOURISH-T as an
      intervention for increasing healthy behaviors of PCS are discussed.

PMID- 29350460
TI  - Three-generation family with novel contiguous gene deletion on chromosome 2p22
      associated with thoracic aortic aneurysm syndrome.
AB  - Latent transforming growth factor binding proteins (LTBP) are a family of
      extracellular matrix glycoproteins that play an important role in the regulation
      of transforming growth factor beta (TGF-beta) activation. Dysregulation of the
      TGF-beta pathway has been implicated in the pathogenesis of inherited disorders
      predisposing to thoracic aortic aneurysms syndromes (TAAS) including Marfan
      syndrome (MFS; FBN1) and Loeys-Dietz syndrome (LDS; TGFBR1, TGFBR2, TGFB2, TGFB3,
      SMAD2, SMAD3). While these syndromes have distinct clinical criteria, they share
      clinical features including aortic root dilation and musculoskeletal findings.
      LTBP1 is a component of the TGF-beta pathway that binds to fibrillin-1 in the
      extracellular matrix rendering TGF-beta inactive. We describe a three-generation
      family case series with a heterozygous ~5.1 Mb novel contiguous gene deletion of
      chromosome 2p22.3-p22.2 involving 11 genes, including LTBP1. The deletion has
      been identified in the proband, father and grandfather, who all have a phenotype
      consistent with a TAAS. Findings include thoracic aortic dilation, ptosis, malar
      hypoplasia, high arched palate, retrognathia, pes planus, hindfoot deformity,
      obstructive sleep apnea, and low truncal tone during childhood with joint laxity
      that progressed to reduced joint mobility over time. While the three affected
      individuals did not meet criteria for either MFS or LDS, they shared features of
      both. Although the deletion includes 11 genes, given the relationship between
      LTBP1, TGF-beta, and fibrillin-1, LTBP1 stands out as one of the possible
      candidate genes for the clinical syndrome observed in this family. More studies
      are necessary to evaluate the potential role of LTBP1 in the pathophysiology of
      TAAS.

PMID- 29350461
TI  - Is testicular irradiation necessary for patients with acute lymphoblastic
      leukemia and testicular relapse?

PMID- 29350462
TI  - Mesoaortic compression of a left-sided inferior vena-cava presenting as recurrent
      pulmonary embolism in a child-a novel anatomic thrombophilia?

PMID- 29350463
TI  - BRIM-P: A phase I, open-label, multicenter, dose-escalation study of vemurafenib
      in pediatric patients with surgically incurable, BRAF mutation-positive melanoma.
AB  - BACKGROUND: Vemurafenib, a selective inhibitor of BRAF kinase, is approved for
      the treatment of adult stage IIIc/IV BRAF V600 mutation-positive melanoma. We
      conducted a phase I, open-label, dose-escalation study in pediatric patients aged
      12-17 years with this tumor type (NCT01519323). PROCEDURE: Patients received
      vemurafenib orally until disease progression. Dose escalation was conducted using
      a 3 + 3 design. Patients were monitored for dose-limiting toxicities (DLTs)
      during the first 28 days of treatment to determine the maximum tolerated dose
      (MTD). Safety/tolerability, tumor response, and pharmacokinetics were evaluated.
      RESULTS: Six patients were enrolled (720 mg twice daily [BID], n = 3; 960 mg BID
      [n = 3]). The study was terminated prematurely due to low enrollment. No DLTs
      were observed; thus, the MTD could not be determined. All patients experienced at
      least one adverse event (AE); the most common were diarrhea, headache,
      photosensitivity, rash, nausea, and fatigue. Three patients experienced serious
      AEs, one patient developed secondary cutaneous malignancies, and five patients
      died following disease progression. Mean steady-state plasma concentrations of
      vemurafenib following 720 mg and 960 mg BID dosing were similar or higher,
      respectively, than in adults. There were no objective responses. Median
      progression-free survival and overall survival were 4.4 months (95% confidence
      interval [CI] = 2.7-5.2) and 8.1 months (95% CI = 5.1-12.0), respectively.
      CONCLUSIONS: A recommended and effective dose of vemurafenib for patients aged 12
      17 years with metastatic or unresectable melanoma was not identified. Extremely
      low enrollment in this trial highlights the importance of considering the
      inclusion of adolescents with adult cancers in adult trials.

PMID- 29350464
TI  - Predictors of response, progression-free survival, and overall survival using
      NANT Response Criteria (v1.0) in relapsed and refractory high-risk neuroblastoma.
AB  - PURPOSE: The New Approaches to Neuroblastoma Therapy Response Criteria (NANTRC)
      were developed to optimize response assessment in patients with
      recurrent/refractory neuroblastoma. Response predictors and associations of the
      NANTRC version 1.0 (NANTRCv1.0) and prognostic factors with outcome were
      analyzed. METHODS: A retrospective analysis was performed of patients with
      recurrent/refractory neuroblastoma enrolled from 2000 to 2009 on 13 NANT Phase
      1/2 trials. NANTRC overall response integrated CT/MRI (Response Evaluation
      Criteria in Solid Tumors [RECIST]), metaiodobenzylguanidine (MIBG; Curie
      scoring), and percent bone marrow (BM) tumor (morphology). RESULTS: Fourteen
      (6.9%) complete response (CR) and 14 (6.9%) partial response (PR) occurred among
      203 patients evaluable for response. Five-year progression-free survival (PFS)
      was 16 +/- 3%; overall survival (OS) was 27 +/- 3%. Disease sites at enrollment
      included MIBG-avid lesions (100% MIBG trials; 84% non-MIBG trials), measurable
      CT/MRI lesions (48%), and BM (49%). By multivariable analysis, Curie score of 0
      (P < 0.001), lower Curie score (P = 0.003), no measurable CT/MRI lesions (P =
      0.044), and treatment on peripheral blood stem cell (PBSC) supported trials (P =
      0.005) were associated with achieving CR/PR. Overall response of stable disease
      (SD) or better was associated with better OS (P < 0.001). In multivariable
      analysis, MYCN amplification (P = 0.037) was associated with worse PFS;
      measurable CT/MRI lesions (P = 0.041) were associated with worse OS; prior
      progressive disease (PD; P < 0.001/P < 0.001), Curie score >= 1 (P < 0.001; P =
      0.001), higher Curie score (P = 0.048/0.037), and treatment on non-PBSC trials (P
      = < 0.001/0.003) were associated with worse PFS and OS. CONCLUSIONS: NANTRCv1.0
      response of at least SD is associated with better OS in patients with
      recurrent/refractory neuroblastoma. Patient and tumor characteristics may predict
      response and outcome. Identifying these variables can optimize Phase 1/2 trial
      design to select novel agents for further testing.

PMID- 29350465
TI  - Proteomics Analysis of Skeletal Muscle from Leptin-Deficient ob/ob Mice Reveals
      Adaptive Remodeling of Metabolic Characteristics and Fiber Type Composition.
AB  - Skeletal muscle insulin resistance, an early metabolic defect in the pathogenesis
      of type 2 diabetes (T2D), may be a cause or consequence of altered protein
      expression profiles. Proteomics technology offers enormous promise to investigate
      molecular mechanisms underlying pathologies, however, the analysis of skeletal
      muscle is challenging. Using state-of-the-art multienzyme digestion and filter
      aided sample preparation (MED-FASP) and a mass spectrometry (MS)-based workflow,
      we performed a global proteomics analysis of skeletal muscle from leptin
      deficient, obese, insulin resistant (ob/ob) and lean mice in mere two fractions
      in a short time (8 h per sample). We identified more than 6000 proteins with 118
      proteins differentially regulated in obesity. This included protein kinases,
      phosphatases, and secreted and fiber type associated proteins. Enzymes involved
      in lipid metabolism in skeletal muscle from ob/ob mice were increased, providing
      evidence against reduced fatty acid oxidation in lipid-induced insulin
      resistance. Mitochondrial and peroxisomal proteins, as well as components of
      pyruvate and lactate metabolism, were increased. Finally, the skeletal muscle
      proteome from ob/ob mice displayed a shift toward the "slow fiber type." This
      detailed characterization of an obese rodent model of T2D demonstrates an
      efficient workflow for skeletal muscle proteomics, which may easily be adapted to
      other complex tissues.

PMID- 29350466
TI  - Simultaneous extraction and determination of trace amounts of diclofenac from
      whole blood using supported liquid membrane microextraction and fast Fourier
      transform voltammetry.
AB  - A novel, simple, and inexpensive analytical technique based on flat sheet
      supported liquid membrane microextraction coupled with fast Fourier transform
      stripping cyclic voltammetry on a reduced graphene oxide carbon paste electrode
      was used for the extraction and online determination of diclofenac in whole
      blood. First, diclofenac was extracted from blood samples using a
      polytetrafluoroethylene membrane impregnated with 1-octanol and then into an
      acceptor solution, subsequently it was oxidized on a carbon paste electrode
      modified with reduced graphene oxide nanosheets. The optimal values of the key
      parameters influencing the method were as follows: scan rate, 6 V/s; stripping
      potential, 200 mV; stripping time, 5 s; pH of the sample solution, 5; pH of the
      acceptor solution,7; and extraction time, 240 min. The calibration curves were
      plotted for the whole blood samples and the method was found to have a good
      linearity within the range of 1-25 MUg/mL with a determination coefficient of
      0.99. The limits of detection and quantification were 0.1 and 1.0 MUg/mL,
      respectively. Using this coupled method, the extraction and determination were
      merged into one step. Accordingly, the speed of detection for sensitive
      determination of diclofenac in complex samples, such as blood, increased
      considerably.

PMID- 29350467
TI  - Alveolar soft part sarcoma in children and young adults: A report of 69 cases.
AB  - BACKGROUND: Alveolar soft part sarcoma (ASPS) is a rare mesenchymal tumor
      characterized by ASPL-TFE3 translocation. Apart from complete surgical resection,
      there is no standard management strategy. PROCEDURE: The clinical data of 69
      children and young adults less than 30 years old with ASPS diagnosed from 1980
      2014 were retrospectively collected from four major institutions. RESULTS: Median
      age at diagnosis was 17 years (range: 1.5-30). Forty-four (64%) were female.
      Median follow-up was 46 months (range: 1-409). Most common primary sites were
      limbs (58%) and trunk (24%). ASPL-TFE3 translocation was present in all 26
      patients tested. IRS postsurgical staging was I in 19 (28%), II in 7 (10%), III
      in 5 (7%), and IV in 38 (55%) patients. The 5-year event-free survival (EFS) and
      overall survival (OS) were 38% and 72%, respectively. The 5-year EFS and OS were
      80% and 87%, respectively, for the 31 patients with localized tumors (IRS-I-II
      III), and 7% and 61%, respectively, for the 38 patients with metastatic tumors
      (IRS-IV). Of 11 IRS-IV patients who received targeted therapy upfront, two had
      partial response, six had stable disease, and three had progressive disease.
      Median time to progression for IRS-IV patients was 12 months for those treated
      with targeted therapy, 7 months for cytotoxic chemotherapy (N = 15), and 4 months
      for observation only (N = 6). CONCLUSION: Localized ASPS has a good prognosis
      after gross total resection. ASPS is resistant to cytotoxic chemotherapy.
      Although there are no curative therapies for patients with metastatic disease,
      prolonged disease stabilization may be achieved with targeted therapies.

PMID- 29350469
TI  - In vitro to in vivo benchmark dose comparisons to inform risk assessment of
      quantum dot nanomaterials.
AB  - Engineered nanomaterials are currently under review for their potential toxicity;
      however, their use in consumer/commercial products has continued to outpace risk
      assessments. In vitro methods may be utilized as tools to improve the efficiency
      of risk assessment approaches. We propose a framework to compare relationships
      between previously published in vitro and in vivo toxicity assessments of cadmium
      selenium containing quantum dots (QDs) using benchmark dose (BMD) and dosimetric
      assessment methods. Although data were limited this approach was useful for
      identifying sensitive assays and strains. In vitro studies assessed effects of
      QDs in three pulmonary cell types across two mouse strains. Significant dose
      response effects were modeled and a standardized method of BMD analysis was
      performed as a function of both exposure dose and dosimetric dose. In vivo
      studies assessed pulmonary effects of QD exposure across eight mouse strains. BMD
      analysis served as a basis for relative comparison with in vitro studies. We
      found consistent responses in common endpoints between in vitro and in vivo
      studies. Strain sensitivity was consistent between in vitro and in vivo studies,
      showing A/J mice more sensitive to QDs. Cell types were found to differentially
      take up QDs. Dosimetric adjustments identified similar sensitivity among cell
      types. Thus, BMD analysis can be used as an effective tool to compare the
      sensitivity of different strains, cell types, and assays to QDs. These methods
      allow for in vitro assays to be used to predict in vivo responses, improve the
      efficiency of in vivo studies, and allow for prioritization of nanomaterial
      assessments. This article is categorized under: Toxicology and Regulatory Issues
      in Nanomedicine > Toxicology of Nanomaterials Toxicology and Regulatory Issues in
      Nanomedicine > Regulatory and Policy Issues in Nanomedicine.

PMID- 29350470
TI  - Specific expression of PD-L1 in RELA-fusion supratentorial ependymoma:
      Implications for PD-1-targeted therapy.
AB  - BACKGROUND: A desperate need for novel therapies in pediatric ependymoma (EPN)
      exists, as chemotherapy remains ineffective and radiotherapy often fails. EPN
      have significant infiltration of immune cells, which correlates with outcome.
      Immune checkpoint inhibitors provide an avenue for new treatments. This study
      characterizes tumor-infiltrating immune cells in EPN and aims at predicting
      candidates for clinical trials using checkpoint inhibitors targeting PD-L1/PD-1
      (programmed death ligand 1/programmed death 1). METHODS: The transcriptomic
      profiles of the primary study cohort of EPN and other pediatric brain tumors were
      interrogated to identify PD-L1 expression levels. Transcriptomic findings were
      validated using the western blotting, immunohistochemistry and flow cytometry.
      RESULTS: We evaluated PD-L1 mRNA expression across four intracranial subtypes of
      EPN in two independent cohorts and found supratentorial RELA fusion (ST-RELA)
      tumors to have significantly higher levels. There was a correlation between high
      gene expression and protein PD-L1 levels in ST-RELA tumors by both the western
      blot and immunohistochemisty. The investigation of EPN cell populations revealed
      PD-L1 was expressed on both tumor and myeloid cells in ST-RELA. Other subtypes
      had little PD-L1 in either tumor or myeloid cell compartments. Lastly, we
      measured PD-1 levels on tumor-infiltrating T cells and found ST-RELA tumors
      express PD-1 in both CD4 and CD8 T cells. A functional T-cell exhaustion assay
      found ST-RELA T cells to be exhausted and unable to secrete IFNgamma on
      stimulation. CONCLUSIONS: These findings in ST-RELA suggest tumor evasion and
      immunsuppression due to PD-L1/PD-1-mediated T-cell exhaustion. Trials of
      checkpoint inhibitors in EPN should be enriched for ST-RELA tumors.

PMID- 29350471
TI  - Variability Assessment of 90 Salivary Proteins in Intraday and Interday Samples
      from Healthy Donors by Multiple Reaction Monitoring-Mass Spectrometry.
AB  - PURPOSE: Saliva is an attractive sample source for the biomarker-based testing of
      several diseases, especially oral cancer. Here, we sought to apply multiplexed LC
      MRM-MS to precisely quantify 90 disease-related proteins and assess their intra-
      and interindividual variability in saliva samples from healthy donors.
      EXPERIMENTAL DESIGN: We developed two multiplexed LC-MRM-MS assays for 122
      surrogate peptides representing a set of disease-related proteins. Saliva samples
      were collected from 10 healthy volunteers at three different time points (Day 1
      morning and afternoon, and Day 2 morning). Each sample was spiked with a constant
      amount of a 15 N-labeled protein and analyzed by MRM-MS in triplicate.
      Quantitative results from LC-MRM-MS were calculated by single-point
      quantification with reference to a known amount of internal standard (heavy
      peptide). RESULTS: The CVs for assay reproducibility and technical variation were
      13 and 11%, respectively. The average concentrations of the 99 successfully
      quantified proteins ranged from 0.28 +/- 0.58 ng mL-1 for profilin-2 (PFN2) to
      8.55 +/-8.96 MUg mL-1 for calprotectin (S100A8). For the 90 proteins detectable
      in >50% of samples, the average CVs for intraday, interday, intraindividual, and
      interindividual samples were 38%, 43%, 45%, and 69%, respectively. The
      fluctuations of most target proteins in individual subjects were found to be
      within +/- twofold. CONCLUSIONS AND CLINICAL RELEVANCE: Our study elucidated the
      intra- and interindividual variability of 90 disease-related proteins in saliva
      samples from healthy donors. The findings may facilitate the further development
      of salivary biomarkers for oral and systemic diseases.

PMID- 29350473
TI  - 2018: An update on JOPM progress over the last year.

PMID- 29350472
TI  - The chemistry and pharmacology of synthetic cannabinoid SDB-006 and its
      regioisomeric fluorinated and methoxylated analogs.
AB  - Synthetic cannabinoids are the largest and most structurally diverse class of new
      psychoactive substances, with manufacturers often using isomerism to evade
      detection and circumvent legal restriction. The regioisomeric methoxy- and
      fluorine-substituted analogs of SDB-006 (N-benzyl-1-pentyl-1H-indole-3
      carboxamide) were synthesized and could not be differentiated by gas
      chromatography-mass spectrometry (GC-MS), but were distinguishable by liquid
      chromatography-quadrupole time-of-flight-MS (LC-QTOF-MS). In a fluorescence-based
      plate reader membrane potential assay, SDB-006 acted as a potent agonist at human
      cannabinoid receptors (CB1 EC50 = 19 nM). All methoxy- and fluorine-substituted
      analogs showed reduced potency compared to SDB-006, although the 2-fluorinated
      analog (EC50 = 166 nM) was comparable to known synthetic cannabinoid RCS-4 (EC50
      = 146 nM). Using biotelemetry in rats, SDB-006 and RCS-4 evoked comparable
      reduction in body temperature (~0.7 degrees C at a dose of 10 mg/kg), suggesting
      lower potency than the recent synthetic cannabinoid AB-CHMINACA (>2 degrees C, 3
      mg/kg).

PMID- 29350474
TI  - Happy Times for the Macromolecular Journals.

PMID- 29350475
TI  - Water deficit disrupts male gametophyte development in Quercus ilex.
AB  - Tree species distribution, and hence forest biodiversity, relies on the
      reproductive capacity of trees, which is currently affected by climate change.
      Drought-induced pollen sterility could increase as a consequence of more intense
      and more frequent droughts projected for temperate and Mediterranean regions, and
      threaten the sexual regeneration of trees in these regions. To evaluate this
      possibility, we examined the effect of long-term partial rainfall exclusion (-27%
      precipitation) on male reproductive development in holm oak, Quercus ilex, one of
      the most important and widespread tree species of the Mediterranean region. We
      examined anther area, pollen production, pollen abortion as well as viable pollen
      production in control and dry treatments. Microscopic examinations revealed
      significant differences in pollen development between trees in the dry and the
      control treatments, even though anthesis occurred before the onset of annual
      drought. Our results demonstrate that anthers collected from Q. ilex trees in the
      dry treatment, which experienced long-term increased drought stress especially
      during the summer, were the same size as anthers in the control treatment, but
      displayed 25% pollen abortion and almost 20% reduction in pollen production.
      Subsequently, the number of viable pollen grains in anthers from dry treatment
      was 35% less than in control. These results suggest a carry-over effect of
      drought stress on pollen production that could reduce the reproductive success of
      Q. ilex. The results have broad implications for better understanding of the
      determinants of tree reproduction by masting and anticipate the outcomes of
      expected drought increase in the Mediterranean on forest dynamics.

PMID- 29350477
TI  - Pharmacokinetic evaluation and safety of topical 1% morphine sulfate application
      on the healthy equine eye.
AB  - OBJECTIVE: To determine if corneal epithelial cell integrity is detrimentally
      affected by short-term administration of 1.0% morphine sulfate. Additionally, we
      sought to determine if topical 1.0% morphine applied to the equine cornea would
      result in ocular or systemic absorption. ANIMAL STUDIED: Six healthy horses.
      PROCEDURE: Morphine sulfate (1.0%) was applied topically to one eye every four
      hours for 72 h before horses were euthanized. Serum samples were collected at
      varying time points during the study and aqueous and vitreous humor were
      collected immediately after euthanasia. Morphine quantification in serum,
      aqueous, and vitreous humor was performed by ELISA. Treated and control corneas
      were submitted for histopathology. Horses were monitored for adverse ocular and
      systemic effects throughout the study period. RESULTS: All horses developed mild
      mucoid ocular discharge in the treated eye. One horse developed a fever during
      treatment. Morphine was detected in the aqueous humor of the treated eye for all
      horses with mean +/- standard deviation of 165.18 ng/mL +/- 87.69 ng/mL. Morphine
      was detected in vitreous humor of the treated eye of 5 of 6 horses with mean +/-
      standard deviation of 4.87 +/- 4.46 ng/mL. Morphine was detected in the serum of
      5 of 6 horses at varying time points. Maximum systemic concentration reached in a
      single horse was 6.98 ng/mL. Corneal histopathology revealed no difference in
      microscopic appearance between morphine-treated and control corneas. CONCLUSIONS:
      Topical administration of 1.0% morphine sulfate did not appear to cause any
      significant ocular or systemic adverse effects. Topical ophthalmic morphine
      application resulted in both ocular and systemic absorption.

PMID- 29350476
TI  - Investigating the mechanisms underlying phytoprotection by plant growth-promoting
      rhizobacteria in Spartina densiflora under metal stress.
AB  - Pollution of coasts by toxic metals and metalloids is a worldwide problem for
      which phytoremediation using halophytes and associated microbiomes is becoming
      relevant. Metal(loid) excess is a constraint for plant establishment and
      development, and plant growth promoting rhizobacteria (PGPR) mitigate plant
      stress under these conditions. However, mechanisms underlying this effect remain
      elusive. The effect of toxic metal(loid)s on activity and gene expression of ROS
      scavenging enzymes in roots of the halophyte Spartina densiflora grown on real
      polluted sediments in a greenhouse experiment was investigated. Sediments of the
      metal-polluted joint estuary of Tinto and Odiel rivers and control, unpollutred
      samples from the Piedras estuary were collected and submitted to ICP-OES. Seeds
      of S. densiflora were collected from the polluted Odiel marshes and grown in
      polluted and unpolluted sediments. Rhizophere biofilm-forming bacteria were
      selected based on metal tolerance and inoculated to S. densiflora and grown for 4
      months. Fresh or frozen harvested plants were used for enzyme assays and gene
      expression studies, respectively. Metal excess induced SOD (five-fold increase),
      whereas CAT and ascorbate peroxidase displayed minor induction (twofold). A
      twofold increase of TBARs indicated membrane damage. Our results showed that
      metal-resistant PGPR (P. agglomerans RSO6 and RSO7 and B. aryabhattai RSO25)
      contributed to alleviate metal stress, as deduced from lower levels of all
      antioxidant enzymes to levels below those of non-exposed plants. The oxidative
      stress index (OSI) decreased between 50 and 75% upon inoculation. The results
      also evidenced the important role of PAL, involved in secondary metabolism and/or
      lignin synthesis, as a pathway for metal stress management in this halophyte upon
      inoculation with appropriate PGPR, since the different inoculation treatments
      enhanced PAL expression between 3.75- and five-fold. Our data confirm, at the
      molecular level, the role of PGPR in alleviating metal stress in S. densiflora
      and evidence the difficulty of working with halophytes for which little genetic
      information is available.

PMID- 29350478
TI  - Enzymatic scarification of Anacamptis morio (Orchidaceae) seed facilitates lignin
      degradation, water uptake and germination.
AB  - The seed coat of many species contains hydrophobic lignins, and in soil the
      action of microbial ligninases may contribute to release from dormancy.
      Laboratory use of ligninases to stimulate germination is promising because of the
      specific action on the seed coat, whereas chemical scarification agents may also
      corrode the embryo. We hypothesised that exposure of Anacamptis morio
      (Orchidaceae) seeds to fungal laccase would stimulate germination, and that the
      mechanism involves lignin degradation and increased imbibition. Germination
      capacity in vitro was quantified with 1 U filter-sterilised laccase added to agar
      medium following autoclaving, compared to a 10% bleach solution (standard bleach
      surface sterilisation/scarification method used in orchid seed sowing). Lignin
      degradation was quantified using an optical method (phloroglucinol-HCl staining)
      combined with image analysis, following experimental pre-treatments involving
      immersion in laccase solution, distilled water (negative control) or bleach
      (positive control). Water uptake after experimental treatments was quantified as
      the proportion of seeds exhibiting visible uptake of an aqueous fluorochrome
      under UV excitation. Laccase stimulated a doubling of germination in vitro with
      respect to bleach surface sterilisation/scarification alone, from 23.7 to 49.8%
      (P = 0.007). Laccase and bleach methods both significantly decreased the optical
      signal of phloroglucinol (for laccase, to 79.9 +/- 1.3% of controls; anova: F =
      10.333, P = 0.002). Laccase resulted in a modest but highly significant (P <
      0.0001) increase in water uptake with respect to the control (11.7%; cf 99.4% for
      bleach). Laccase scarification can stimulate germination of A. morio through a
      mechanism of targeted seed coat degradation. The results demonstrate the
      potential of this relatively non-invasive enzymatic scarification technique.

PMID- 29350479
TI  - Solution Processable 1D Fullerene C60 Crystals for Visible Spectrum
      Photodetectors.
AB  - Visible spectrum photodetector devices fabricated using molecular crystals of
      carbon C60 are reported. The devices operate efficiently, extending over and
      beyond the full visible light spectrum (300-710 nm) with a bias voltage tunable
      responsivity of 4 mA-0.5 mA W-1 . Across this range of wavelengths, the noise
      equivalent power of these devices remains below 102 nW Hz-1/2 , providing a
      detectivity of 107 Jones. The noise current in these devices is found to have a
      strong dependence on both bias voltage and frequency, varying by 4 orders of
      magnitude from 1 nA Hz-1/2 to 0.1 pA Hz-1/2 . The devices also display a near
      linear dependence of photocurrent on light intensity over 4 orders of magnitude,
      providing a dynamic range approaching 80 dB. The 3 dB bandwidth of the devices is
      found to be above 102 Hz, while the 18 dB bandwidth exceeds 1 kHz. The transient
      photocurrents of the devices have a rise time of ~50 us and a long fall time of
      ~4 ms. The spectral photocurrent of the devices is found to quench gradually with
      a reduction in temperature from ~300 K and is fully quenched at temperatures
      below T ~ 100 K. Upon reheating, the device performance is fully recovered.

PMID- 29350480
TI  - Unilateral Wilms tumor: The relevance of pre- and postnephrectomy evaluation of
      renal function.

PMID- 29350481
TI  - Emotion regulation and positive affect in the context of salivary alpha-amylase
      response to pain in children with cancer.
AB  - BACKGROUND: Children with cancer routinely undergo painful medical procedures
      invoking strong physiological stress responses. Resilience to this pain may be
      conferred through resources such as emotion regulation strategies and positive
      affect. PROCEDURE: This study measured dispositional positive affect in children
      with cancer (N = 73) and randomly assigned participants to one of three emotion
      regulation strategy conditions (distraction, reappraisal, or reassurance).
      Children applied their assigned strategy during an experimental pain procedure
      (the cold pressor task [CPT]) and provided saliva samples before, immediately
      after, and 15 min after the CPT. Saliva samples were later assayed for salivary
      alpha amylase (sAA)-a surrogate marker for autonomic/sympathetic nervous system
      activity and regulation. RESULTS: Children in the reassurance group had sAA
      levels that continued to rise after completion of the CPT compared to children in
      the distraction (b = -1.68, P = 0.021) and reappraisal conditions (b = -1.24, P =
      0.084). Furthermore, dispositional positive affect moderated the effect of
      condition such that children in the reassurance group with lower levels of
      positive affect had sAA levels that continued to rise after completion of the CPT
      (dy/dx = 1.56, P = 0.027), whereas children in the reassurance condition with
      higher levels of positive affect did not exhibit this rise (P > 0.05).
      CONCLUSIONS: Specific emotion regulation strategies, such as distraction and
      reappraisal, may attenuate the stress response to pain in pediatric patients with
      cancer, and positive affect may confer resilience in response to pain even with
      use of less effective coping strategies such as reassurance.

PMID- 29350482
TI  - Erratum.

PMID- 29350483
TI  - Robert F. Schmidt Ph.D., Prof. Dr. med. D. Sc. h.c. 1932-2017 Facets of a life
      for science.

PMID- 29350484
TI  - Paraptosis-Inducing Nanomedicine Overcomes Cancer Drug Resistance for a Potent
      Cancer Therapy.
AB  - Most chemotherapeutic drugs and their nanomedicine formulations exert anticancer
      activity by inducing cancer cell apoptosis. However, cancer cells inherently have
      and acquire many antiapoptosis mechanisms, causing cancer drug resistance and
      poor prognoses in patients. Herein, a potent paraptosis-inducing nanomedicine is
      reported that causes quick nonapoptotic death of cancer cells, overcoming
      apoptosis-based resistance and effectively inhibiting drug-resistant tumor
      growth. The nanomedicine is composed of micelles made from an amphiphilic 8
      hydroxyquinoline (HQ)-conjugate block copolymer with polyethylene glycol. Cu2+
      can catalyze the hydrolysis of the HQ conjugation linker and liberate HQ, and
      these molecules can form the complex Cu(HQ)2 , a strong proteasome inhibitor
      effective at inducing cell paraptosis. In vivo, the Cu2+ -responsive HQ-releasing
      micelles respond to elevated tumor Cu2+ levels or externally administered Cu2+
      and effectively inhibit the growth of human breast adenocarcinoma doxorubicin
      resistant (MCF-7/ADR) tumors. Compared with other nanomedicines that overcome
      drug resistance via delivering several agents or even siRNA, this paraptosis
      inducing nanomedicine provides a simple but potent approach to overcoming cancer
      drug resistance.

PMID- 29350485
TI  - Purification of glutathione S-transferase enzyme from quail liver tissue and
      inhibition effects of (3aR,4S,7R,7aS)-2-(4-((E)-3-(aryl)acryloyl)phenyl)
      3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione derivatives on the
      enzyme activity.
AB  - The use of quail meat and eggs has made this animal important in recent years,
      with its low cost and high yields. Glutathione S-transferases (GST, E.C.2.5.1.18)
      are an important enzyme family, which play a critical role in detoxification
      system. In our study, GST was purified from quail liver tissue with 47.88-fold
      purification and 12.33% recovery by glutathione agarose affinity chromatography.
      The purity of enzyme was checked by SDS-PAGE method and showed a single band. In
      addition, inhibition effects of (3aR,4S,7R,7aS)-2-(4-((E)-3
      (aryl)acryloyl)phenyl)-3a,4,7,7a-tetrahydro-1H-4,7methanoisoindole-1,3(2H)-dion
      derivatives (1a-g) were investigated on the enzyme activity. The inhibition
      parameters (IC50 and Ki values) were calculated for these compounds. IC50 values
      of these derivatives (1a-e) were found as 23.00, 15.75, 115.50, 10.00, and 28.75
      MUM, respectively. Ki values of these derivatives (1a-e) were calculated in the
      range of 3.04 +/- 0.50 to 131.50 +/- 32.50 MUM. However, for f and g compounds,
      the inhibition effects on the enzyme were not found.

PMID- 29350486
TI  - Inflammatory response and treatment tolerance of long-term infusion of the anti
      GD2 antibody ch14.18/CHO in combination with interleukin-2 in patients with high
      risk neuroblastoma.
AB  - BACKGROUND: The monoclonal anti-GD2 antibody ch14.18/CHO in combination with IL-2
      is active and effective in high-risk neuroblastoma (NB) patients. Here, we
      investigated the inflammatory response and treatment tolerance of long-term
      infusion (LTI) of ch14.18/CHO (10 * 10 mg/m2 ; 24 hr) in combination with
      subcutaneous (s.c.) IL-2 in a single center program. METHODS: Fifty-three NB
      patients received up to six cycles of 100 mg/m2 ch14.18/CHO (d8-18, where d
      represents day(s)) as LTI combined with 6 * 106 IU/m2 s.c. IL-2 (d1-5; 8-12) and
      160 mg/m2 oral 13-cis retinoic acid (RA) (d19-32). Side effects of ch14.18/CHO
      and IL-2 treatment require hospitalization of patients on d8. Treatment tolerance
      was evaluated daily with clinical parameters (body temperature, vital signs,
      Lansky performance status, requirement of i.v. concomitant medication) to define
      an outpatient candidate status. sIL-2-R and C-reactive protein values were
      determined to assess the inflammatory response. RESULTS: LTI of ch14.18/CHO (d8
      18) in combination with s.c.IL-2 (d8-12) showed an acceptable treatment tolerance
      that allowed all patients to receive part of the treatment as an outpatient
      (median time point of discharge: d15 for all cycles). The treatment tolerance
      improved from cycle to cycle and the time to become an outpatient candidate
      decreased from d15 to d13 in subsequent cycles. Clinical and laboratory
      parameters indicate a maximum inflammatory response at d11 of each cycle.
      Interestingly, the soluble IL-2 receptor remained increased at baseline of the
      next cycle indicating immune activation over the entire treatment period of 6
      months. CONCLUSIONS: LTI of ch14.18/CHO combined with s.c.IL-2 shows an improved
      tolerance in subsequent cycles allowing outpatient treatment.

PMID- 29350487
TI  - Pediatric patients with cutaneous melanoma: A European study.
AB  - INTRODUCTION: Cutaneous melanoma is rare in childhood and published studies have
      mainly been retrospective single-institution series or small case series. Given
      the absence of clinical protocols dedicated to pediatric melanoma, the treatment
      approach is generally extrapolated from the ones applied to adults. METHODS:
      Coordinated by the European Cooperative Study Group for Pediatric Rare Tumors
      (EXPeRT), this study collected patients prospectively registered between 2002 and
      2012 under national cooperative projects dedicated to rare pediatric tumors in
      Italy, Poland, Germany, and France. Additional cases were collected from
      dermatology registries in Germany and Israel. RESULTS: A total of 219 patients
      aged 0-18 years (median 14.4) were included in the analysis. Sentinel lymph node
      biopsy was performed in 112 patients (76% of those with Breslow thickness > 0.75
      mm) and was positive in 37.5%. Systemic therapy was used in 33 cases. In stage
      III cases, survival rates were similar for patients who received (23 cases) or
      not (21 cases) adjuvant therapy. For the whole series, 3-year overall and disease
      free survival rates were 91.4% and 84.0%, respectively (median follow-up 41.8
      months). Tumor site, tumor stage, and ulceration influenced survival rates.
      Patients treated by pediatric oncologists (n = 140) were more likely to have
      advanced disease than those treated by dermatologists (n = 79). DISCUSSION: This
      study would suggest that the clinical history of melanoma in children and
      adolescents might resemble that of adult counterpart. Cooperative efforts are
      needed to make new drugs more readily available to pediatric patients to increase
      the outcome of patient with advanced disease.